PMID- 23530731
TI  - Agomelatine, a novel intriguing antidepressant option enhancing neuroplasticity:
      a critical review.
AB  - OBJECTIVES: The treatment of major affective disorders, commonly associated with
      high disability and elevated social costs may be still considered unsatisfactory.
      Among all antidepressant drugs, predominantly acting through monoaminergic
      mechanisms, agomelatine is of particular interest due to another alternative
      mechanism of action. Targeting melatonergic receptors, agomelatine play a crucial
      role in synchronizing circadian rhythms, known to be altered in depressed
      subjects. METHODS: A critical review of the literature focusing on efficacy,
      safety and tolerability of agomelatine in major affective disorders was
      performed. Additionally, we focused on the potential of agomelatine in enhancing
      neuroplasticity mechanisms and promote neurogenesis. A total of 136 articles from
      peer-reviewed journals were identified, of which 50 were assessed for eligibility
      and 21 were included. RESULTS: Agomelatine, a melatonergic analogue drug acting
      as MT1/MT2 agonist and 5-HT2C antagonist, has been reported to be effective as
      antidepressant drug. Studies confirmed not only clinical efficacy but also safety
      and tolerability of agomelatine. Also, it enhances neuroplasticity mechanisms and
      adult neurogenesis in brain areas such as hippocampus and prefrontal cortex.
      CONCLUSIONS: Agomelatine actually represents an intriguing option in the
      treatment of affective disorders.

PMID- 23530732
TI  - Pharmacogenomic predictors of citalopram treatment outcome in major depressive
      disorder.
AB  - OBJECTIVES: A significant proportion of patients with major depressive disorder
      (MDD) do not improve following treatment with first-line antidepressants and,
      currently, there are no objective indicators of predictors of antidepressant
      response. The aim of this study was to investigate pre-treatment peripheral gene
      expression differences between future remitters and non-responders to citalopram
      treatment and identify potential pharmacogenomic predictors of response. METHODS:
      We conducted a gene expression study using Affymetrix HG-U133 Plus2 microarrays
      in peripheral blood samples from untreated individuals with MDD (N = 77),
      ascertained at a community outpatient clinic, prior to an 8-week treatment with
      citalopram. Gene expression differences were assessed between remitters and non
      responders to treatment. Technical validation of significant probesets was
      carried out by qRT-PCR. RESULTS: A total of 434 probesets displayed significant
      correlation to change in score and 33 probesests were differentially expressed
      between eventual remitters and non-responders. Probesets for SMAD 7 (SMA- and MAD
      related protein 7) and SIGLECP3 (sialic acid-binding immunoglobulin-like lectin,
      pseudogene 3) were the most significant differentially expressed genes following
      FDR correction, and both were down-regulated in individuals who responded to
      treatment. CONCLUSIONS: These findings point to SMAD7 and SIGLECP3 as candidate
      predictive biomarkers of antidepressant response.

PMID- 23530733
TI  - To the beat of a different drum: determinants implicated in the asymmetric
      sequence divergence of Caenorhabditis elegans paralogs.
AB  - BACKGROUND: Gene duplicates often exhibit asymmetric rates of molecular evolution
      in their early evolutionary existence. This asymmetry in rates is thought to
      signify the maintenance of the ancestral function by one copy and the removal of
      functional constraint on the other copy, enabling it to embark on a novel
      evolutionary trajectory. Here I focused on a large population of evolutionarily
      young gene duplicates (KS <= 0.14) in the Caenorhabditis elegans genome in order
      to conduct the first combined analysis of four predictors (evolutionary age,
      chromosomal location, structural resemblance between duplicates, and duplication
      span) which may be implicated in the asymmetric sequence divergence of paralogs
      at the nucleotide and amino acid level. In addition, I investigate if either
      paralog is equally likely to embark on a trajectory of accelerated sequence
      evolution or whether the derived paralog is more likely to exhibit faster
      sequence evolution. RESULTS: Three predictors (evolutionary age of duplicates,
      chromosomal location and duplication span) serve as major determinants of
      sequence asymmetry between C. elegans paralogs. Paralogs diverge asymmetrically
      in sequence with increasing evolutionary age, the relocation of one copy to a
      different chromosome and attenuated duplication spans that likely fail to capture
      the entire ancestral repertoire of coding sequence and regulatory elements.
      Furthermore, for paralogs residing on the same chromosome, opposite
      transcriptional orientation and increased genomic distance do not increase
      sequence asymmetry between paralogs. For a subset of duplicate pairs wherein the
      ancestral versus derived paralog could be distinguished, the derived paralogs are
      more likely to evolve at accelerated rates. CONCLUSIONS: This genome-wide study
      of evolutionarily young duplicates stemming primarily from DNA-mediated small
      scale duplication events demonstrates that genomic relocation to a new chromosome
      has important consequences for asymmetric divergence of paralogs, akin to
      paralogs arising from RNA-mediated duplication events. Additionally, the
      duplication span is negatively correlated with sequence rate asymmetry among
      paralogs, suggesting that attenuated duplication spans stemming from incomplete
      duplication of the ORF and/or ancestral regulatory elements further accelerate
      sequence divergence between paralogs. Cumulatively, derived copies exhibit
      accelerated rates of sequence evolution suggesting that they are primed for a
      divergent evolutionary trajectory by changes in structure and genomic context at
      inception.

PMID- 23530734
TI  - On the nature of hypercoordination in dihalogenated perhalocyclohexasilanes.
AB  - Hypercoordination in silicon has long been reviewed. Dihalogenated
      perhalocyclohexasilane inverse sandwich complexes (ISCs) are the only group of
      hypercoordinate Si complexes with anion donors that contact six neutral silicon
      atoms; opening prospective applications in Si self-assembled nanostructures.
      Hypercoordinate bonds in 16 such ISCs were studied and their anion ring
      interactions have been understood with respect to halides. MU(6) mode of
      coordination was confirmed by the presence of 6 equivalent (3,-1) bond critical
      points through Bader's QTAIM perspective. The presence of Lewis acid sites above
      and below the flat Si rings were examined through a reduced density gradient
      (RDG) analysis, and the ability of halide anions (X' = F, Cl, Br, I) to
      hypercoordinate has been understood. Role of the ring halides (X) in tuning size
      and acidity of Lewis sites has been addressed. While the total interaction
      between the two anions and the ring is quantified through EDA, each SiX'
      hypercoordinate bond was identified as either purely ionic or transient through
      QTAIM computations. CDA shows that these complexes are of donor-acceptor type
      with significant back-donation. The analysis shows that BrF' and IF' were found
      to reach maximum covalency within the group. Hence in future, tuning these ISCs
      for construction of nanocrystalline Si structures for optoelectronic properties
      can essentially utilize the collective, weak yet hypercoordinate Si in these
      complexes.

PMID- 23530736
TI  - Assessments and improvements in methods for monitoring seafood safety in response
      to the Deepwater Horizon oil spill.
AB  - As a result of the April 2010 Deepwater Horizon oil spill, sensory testing
      protocols were established for reopening closed seafood harvest areas. In order
      to improve this method and quantitatively assess petrochemical taint, a new
      method using solid phase microextraction (SPME) and a 5975T transportable GC/MS
      was developed. This method can analyze 40 samples per instrument per day and
      could be an alternative to the human sensory panel. In seafood samples collected
      from supermarkets in the Washington D.C. area and the Gulf of Mexico, all
      compounds related to petrochemical taint were below the method detection limit
      (MDL) (0.14-2.6 ng/g). Additionally, to address consumer concerns regarding the
      presence of n-alkanes and iso-alkanes in seafood, these compounds were
      investigated in samples purchased in the Washington D.C. area and the Gulf of
      Mexico. Concentrations in Gulf of Mexico finfish ranged from 0.066 to 1.2 mg/kg,
      which is within the same background range of iso- and n-alkanes measured in
      seafood samples purchased in the Washington D.C. area (0.0072-1.6 MUg/g). These
      automated methods provide a transportable option to obtain rapid results for
      compounds indicative of petroleum taint and iso- and n-alkanes in case of a
      future disaster.

PMID- 23530735
TI  - Treadmill exercise protects against pentylenetetrazol-induced seizures and
      oxidative stress after traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and
      significant resources are required to develop a better understanding of the
      pathologic mechanism as targets for potential therapies. Thus, we decided to
      investigate whether physical exercise after fluid percussion injury (FPI)
      protects from oxidative and neurochemical alterations as well as from behavioral
      electroencephalographic (EEG) seizures induced by subeffective convulsive doses
      of pentylenetetrazol (PTZ; 35 mg/kg). Behavioral and EEG recordings revealed that
      treadmill physical training increased latency to first clonic and tonic-clonic
      seizures, attenuated the duration of generalized seizures, and protected against
      the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. EEG
      recordings also revealed that physical exercise prevented PTZ-induced amplitude
      increase in TBI animals. Neurochemical analysis showed that exercise training
      increased glutathione/oxidized glutathione ratio and glutathione levels per se.
      Exercise training was also effective against alterations in the redox status,
      herein characterized by lipid peroxidation (thiobarbituric acid reactive
      substances), protein carbonyl increase, as well as the inhibition of superoxide
      dismutase and Na+,K+-ATPase activities after FPI. On the other hand, histologic
      analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal
      damage in cerebral cortex 4 weeks after injury and that physical exercise did not
      protect against neuronal injury. These data suggest that the ability of physical
      exercise to reduce FPI-induced seizures is not related to its protection against
      neuronal damage; however, the effective protection of selected targets, such as
      Na+/K+-ATPase elicited by physical exercise, may represent a new line of
      treatment for post-traumatic seizure susceptibility.

PMID- 23530737
TI  - White cell count and platelet count associate with histological alcoholic
      hepatitis in jaundiced harmful drinkers.
AB  - BACKGROUND: Patients with suspected alcoholic hepatitis and a Discriminant
      Function >=32 underwent liver biopsy to confirm the diagnosis. Of these (n = 58),
      43 had histological features of alcoholic hepatitis and 15 (25%) did not.We aimed
      to determine the laboratory features that differentiated those patients with a
      histological diagnosis of alcoholic hepatitis from those without, and assess
      potential clinical utility. METHODS: Laboratory investigations at presentation
      for each of the histologically confirmed cases of alcoholic hepatitis (n = 43)
      were compared to those without (n = 15) to determine whether there were
      differences between the two groups. Univariate analysis was by Mann Whitney U
      Test and Multivariate analysis was by a stepwise approach. RESULTS: White cell
      count (16.2 +/- 10.5 v 6.9 +/- 3.5 (* 109/L); p = 0.0001) and platelet count (178
      +/- 81 v 98.4 +/- 43 (* 109/L); p = 0.0005) were higher in the patients with
      histological features of alcoholic hepatitis than in those without. The area
      under the ROC curve for AH diagnosis was estimated to be 0.83 (0.73, 0.94) and
      0.81 (0.69, 0.93) for white cell count and platelet count respectively.
      CONCLUSIONS: Clinicians cannot accurately differentiate patients with or without
      alcoholic hepatitis without liver biopsy. This is critically important when
      deciding on specific therapies such as corticosteroids or when interpreting data
      from future trials in which biopsy is not mandated. In situations where liver
      biopsy is unsuitable or unavailable the white cell and platelet counts can be
      used to determine the likelihood of histological alcoholic hepatitis and guide
      treatment.

PMID- 23530738
TI  - A review of the factors associated with the non-use of respite services by carers
      of people with dementia: implications for policy and practice.
AB  - The use of respite services by carers has been shown to extend the length of time
      people with dementia can remain living in the community with family support.
      However, the use of respite services by informal carers of people with dementia
      is often low and does not appear to match carer need. To better understand how to
      address carers' unmet need for respite, the factors that impede respite service
      use must be identified. To achieve this, a narrative synthesis of published
      academic literature (1990-2011) was undertaken regarding factors associated with
      not utilising different types of respite services utilising Anderson's
      Behavioural Model of Service Use. The review reinforces the importance of the
      assessment and matching of services to the needs of individual carers and care
      recipients at the local level. It also highlights the need to move beyond care
      pathways for individuals. To support respite use there is a need for local action
      to be augmented at a community or population level by strategies to address
      attitudinal and resource barriers that influence sub-groups of the carer
      population who may be more vulnerable to service non-use. 

PMID- 23530742
TI  - All roads lead to Rome (but some may be harder to travel): SRP-independent
      translocation into the endoplasmic reticulum.
AB  - Translocation into the endoplasmic reticulum (ER) is the first biogenesis step
      for hundreds of eukaryotic secretome proteins. Over the past 30 years,
      groundbreaking biochemical, structural and genetic studies have delineated one
      conserved pathway that enables ER translocation- the signal recognition particle
      (SRP) pathway. However, it is clear that this is not the only pathway which can
      mediate ER targeting and insertion. In fact, over the past decade, several SRP
      independent pathways have been uncovered, which recognize proteins that cannot
      engage the SRP and ensure their subsequent translocation into the ER. These SRP
      independent pathways face the same challenges that the SRP pathway overcomes:
      chaperoning the preinserted protein while in the cytosol, targeting it rapidly to
      the ER surface and generating vectorial movement that inserts the protein into
      the ER. This review strives to summarize the various mechanisms and machineries
      which mediate these stages of SRP-independent translocation, as well as examine
      why SRP-independent translocation is utilized by the cell. This emerging
      understanding of the various pathways utilized by secretory proteins to insert
      into the ER draws light to the complexity of the translocational task, and
      underlines that insertion into the ER might be more varied and tailored than
      previously appreciated.

PMID- 23530743
TI  - Efficient and scalable synthesis of bardoxolone methyl (cddo-methyl ester).
AB  - Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl
      ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti
      inflammatory activity (levels below 1 nM), has completed a successful phase I
      clinical trial for the treatment of cancer and a successful phase II trial for
      the treatment of chronic kidney disease in type 2 diabetes patients. Our
      synthesis of bardoxolone methyl (1) proceeds in ~50% overall yield in five steps
      from oleanolic acid (2), requires only one to two chromatographic purifications,
      and can provide gram quantities of 1.

PMID- 23530744
TI  - Is Europe putting theory into practice? A qualitative study of the level of self
      management support in chronic care management approaches.
AB  - BACKGROUND: Self-management support is a key component of effective chronic care
      management, yet in practice appears to be the least implemented and most
      challenging. This study explores whether and how self-management support is
      integrated into chronic care approaches in 13 European countries. In addition, it
      investigates the level of and barriers to implementation of support strategies in
      health care practice. METHODS: We conducted a review among the 13 participating
      countries, based on a common data template informed by the Chronic Care Model.
      Key informants presented a sample of representative chronic care approaches and
      related self-management support strategies. The cross-country review was
      complemented by a Dutch case study of health professionals' views on the
      implementation of self-management support in practice. RESULTS: Self-management
      support for chronically ill patients remains relatively underdeveloped in Europe.
      Similarities between countries exist mostly in involved providers (nurses) and
      settings (primary care). Differences prevail in mode and format of support, and
      materials used. Support activities focus primarily on patients' medical and
      behavioral management, and less on emotional management. According to Dutch
      providers, self-management support is not (yet) an integral part of daily
      practice; implementation is hampered by barriers related to, among others,
      funding, IT and medical culture. CONCLUSIONS: Although collaborative care for
      chronic conditions is becoming more important in European health systems,
      adequate self-management support for patients with chronic disease is far from
      accomplished in most countries. There is a need for better understanding of how
      we can encourage both patients and health care providers to engage in productive
      interactions in daily chronic care practice, which can improve health and social
      outcomes.

PMID- 23530745
TI  - Drug delivery to hair follicles.
AB  - INTRODUCTION: The optimization of drug delivery to and via the hair follicles is
      gaining more and more importance as it has been recognized that the hair
      follicles are an interesting target site for topical applications. They are
      closely surrounded by capillaries and antigen-presenting cells, are associated
      with the sebaceous glands and are the host of stem cells in the bulge region of
      the hair follicle. AREAS COVERED: The present review shortly summarizes the
      complexity of the structure, biology and functions of the hair follicle and
      presents the models and methods suitable to investigate follicular penetration.
      Drug delivery to hair follicles was clearly shown to be dependent on the
      physicochemical properties of the applied substances and vehicles as well as on
      the activity status, size and density of the hair follicles. Especially
      particulate substances were demonstrated to be proficient drug carriers into the
      hair follicles, whereas dependent data for transfollicular penetration into the
      deeper viable skin layers could only be found for non-particulate substances
      which then, however, received rapid access to the circulation when the follicular
      pathway was accessible. EXPERT OPINION: Promising concepts to optimize hair
      follicle delivery and to beneficially utilize particulate substances for
      efficient follicular drug delivery are the application of external or internal
      stimuli for controlled drug release from the particles such as the combined
      application with protease or the usage of gold nanoparticles in combination with
      near-infrared irradiation.

PMID- 23530746
TI  - Released potential: a qualitative study of the Mental Health Nurse Incentive
      Program in Australia.
AB  - The Mental Health Nurse Incentive Program (MHNIP) is a Commonwealth Government
      funded scheme that supports people living with a mental illness. Despite its
      significance, the program has received little attention from researchers nor
      critical discussion within the published work. This paper first critically
      examines the MHNIP from the contexts of identities, autonomy, and capabilities of
      mental health nurses (MHN) and then reports on findings from a qualitative study
      that explored the experiences of staff working in the MHNIP. Key findings from
      this qualitative study include four main themes indicating that both the program
      and the nurses working within it are addressing the unmet needs of people living
      with a mental illness. They achieve these ends by adopting holistic and consumer
      centred approaches and by providing a wide range of therapeutic interventions. As
      well, the MHN in this study valued the freedom and autonomy of their practice
      outside public health services and the respect received from colleagues working
      in other disciplines. Findings suggest that MHN within the study were experienced
      as having autonomous identities and roles that may be in contrast to the
      restrictive understandings of MHN capability within the program's funding rules. 

PMID- 23530747
TI  - Exploiting the unique ATP-binding pocket of toxoplasma calcium-dependent protein
      kinase 1 to identify its substrates.
AB  - Apicomplexan parasites rely on calcium as a second messenger to regulate a
      variety of essential cellular processes. Calcium-dependent protein kinases
      (CDPK), which transduce these signals, are conserved among apicomplexans but
      absent from mammalian hosts, making them attractive targets for therapeutic
      intervention. Despite their importance, the signaling pathways CDPK regulate
      remain poorly characterized, and their protein substrates are completely unknown.
      In Toxoplasma gondii, CDPK1 is required for calcium-regulated secretion from
      micronemes, thereby controlling motility, invasion, and egress from host cells.
      CDPK1 is unique among parasite and mammalian kinases in containing glycine at the
      key "gatekeeper" residue, which results in an expanded ATP-binding pocket. In the
      present study, we use a synthetic ATPgammaS analogue that displays steric
      complementarity to the ATP-binding pocket and hence allows identification of
      protein substrates based on selective thiophosphorylation. The specificity of
      this approach was validated by the concordance between the identified
      phosphorylation sites and the in vitro substrate preference of CDPK1. We further
      demonstrate that the phosphorylation of predicted substrates is dependent on
      CDPK1 both in vivo and in vitro. This combined strategy for identifying the
      targets of specific protein kinases provides a platform for defining the roles of
      CDPKs in apicomplexans. 

PMID- 23530748
TI  - Evaluation of hypoglycemic and antioxidative effects of synthesized peptide MC62.
AB  - Diabetes mellitus has been considered as a major health problem in the world
      today. This study aimed to investigate the hypoglycemic and antioxidative effects
      of peptide MC62 which was synthesized by solid-phase peptide synthesis method
      against diabetes induced by streptozotocin. MC62 was administered daily and
      injected intraperitoneally to the diabetic mice at a dose of 1 MUmol/kg body
      weight for 20 days. The levels of fasting blood glucose and HbA1C, pancreatic
      islet damage, and associated changes in antioxidative activities were evaluated
      in streptozotocin-induced diabetic mice used the exenatide as positive control.
      After the administration of MC62 together with exenatide for 20 days, the
      elevated fasting blood glucose and HbA1C levels were reduced, and antioxidative
      activities were restored. It was confirmed with the histological finding that
      MC62 prevented the islet from damage in diabetic mice. This indicated that MC62
      can prevent mice from hyperglycemia which may be associated with oxidative
      stress. It also suggested that MC62 could be used as a safe alternative
      hypoglycemic candidate for treatment of diabetes. 

PMID- 23530749
TI  - 53BP1 expression is a modifier of the prognostic value of lymph node ratio and CA
      19-9 in pancreatic adenocarcinoma.
AB  - BACKGROUND: 53BP1 binds to the tumor suppressor p53 and has a key role in DNA
      damage response and repair. Low 53BP1 expression has been associated with
      decreased survival in breast cancer and has been shown to interact with several
      prognostic factors in non-small cell lung cancer. The role of 53BP1 in pancreatic
      ductal adenocarcinoma (PDAC) has yet to be determined. We aimed to investigate
      whether 53BP1 levels interact with established prognostic factors in PDAC.
      METHODS: 106 patients for whom there was tissue available at time of surgical
      resection for PDAC were included. A tissue microarray was constructed using
      surgical specimens, stained with antibodies to 53BP1, and scored for expression
      intensity. Univariate and multivariate statistical analyses were performed to
      investigate the association between 53BP1 and patient survival with known
      prognostic factors for survival. RESULTS: The association of 53BP1 with several
      established prognostic factors was examined, including stage, tumor grade,
      surgical margin, peripancreatic extension, lymph node ratio (LNR), and CA 19-9.
      We found that 53BP1 modified the effects of known prognostic variables including
      LNR and CA 19-9 on survival outcomes. When 53BP1 intensity was low, increased LNR
      was associated with decreased OS (HR 4.84, 95% CI (2.26, 10.37), p<0.001) and
      high CA19-9 was associated with decreased OS (HR 1.72, 95% CI (1.18, 2.51),
      p=0.005). When 53BP1 intensity was high, LNR and CA19-9 were no longer associated
      with OS (p=0.958 and p=0.606, respectively). CONCLUSIONS: In this study, 53BP1, a
      key player in DNA damage response and repair, was found to modify the prognostic
      value of two established prognostic factors, LNR and CA 19-9, suggesting 53BP1
      may alter tumor behavior and ultimately impact how we interpret the value of
      other prognostic factors.

PMID- 23530750
TI  - Current manufactured cigarette smoking and roll-your-own cigarette smoking in
      Thailand: findings from the 2009 Global Adult Tobacco Survey.
AB  - BACKGROUND: Current smoking prevalence in Thailand decreased from 1991 to 2004
      and since that time the prevalence has remained flat. It has been suggested that
      one of the reasons that the prevalence of current smoking in Thailand has stopped
      decreasing is due to the use of RYO cigarettes. The aim of this study was to
      examine characteristics of users of manufactured and RYO cigarettes and dual
      users in Thailand, in order to determine whether there are differences in the
      characteristics of users of the different products. METHODS: The 2009 Global
      Adult Tobacco Survey (GATS Thailand) provides detailed information on current
      smoking patterns. GATS Thailand used a nationally and regionally representative
      probability sample of 20,566 adults (ages 15 years and above) who were chosen
      through stratified three-stage cluster sampling and then interviewed face-to
      face. RESULTS: The prevalence of current smoking among Thai adults was 45.6% for
      men and 3.1% for women. In all, 18.4% of men and 1.0% of women were current users
      of manufactured cigarettes only, while 15.8% of men and 1.7% of women were
      current users of RYO cigarettes only. 11.2% of men and 0.1% of women used both
      RYO and manufactured cigarettes. Users of manufactured cigarettes were younger
      and users of RYO were older. RYO smokers were more likely to live in rural areas.
      Smokers of manufactured cigarettes appeared to be more knowledgeable about the
      health risks of tobacco use. However, the difference was confounded with age and
      education; when demographic variables were controlled, the knowledge differences
      no longer remained. Smokers of manufactured cigarettes were more likely than dual
      users and those who used only RYO to report that they were planning on quitting
      in the next month. Users of RYO only appeared to be more addicted than the other
      two groups as measured by time to first cigarette. CONCLUSIONS: There appears to
      be a need for product targeted cessation and prevention efforts that are directed
      toward specific population subgroups in Thailand and include information on
      manufactured and RYO cigarettes.

PMID- 23530751
TI  - Prognosis and prognostic factors in non-traumatic acute-onset compressive
      mononeuropathies--radial and peroneal mononeuropathies.
AB  - BACKGROUND AND PURPOSE: Little is known about the natural history of non
      traumatic compressive mononeuropathies. To improve patient management, prognostic
      factors and outcome in patients with non-traumatic peroneal and radial
      mononeuropathies were studied. METHODS: Retrospective clinical,
      electrophysiological and sonographic data of patients with non-traumatic peroneal
      and radial mononeuropathies were evaluated. Clinical, electrophysiological and
      sonographic evaluations had to take place 2-12 weeks after symptom onset and
      follow-up had to be for >6 months. RESULTS: Twenty-five patients with peroneal
      mononeuropathy and 58 with radial mononeuropathy were included. Mean follow-up
      was 8.9 +/- 2.4 months. Approximately 90% of patients recovered to a muscle
      strength of British Medical Research Council grade 4 or 5. Multiple logistic
      regression analysis revealed conduction block on nerve conduction studies,
      younger age and less severe initial weakness as indicators for a good prognosis.
      Peripheral nerve ultrasound was not prognostic in the 40 patients where it was
      available. CONCLUSIONS: The present study shows a good prognosis for spontaneous
      recovery after non-traumatic acute-onset compressive peroneal and radial
      mononeuropathies. Patients with denervation on needle electromyography, older age
      and severe initial weakness have a poorer prognosis and should be closely
      monitored to facilitate timely surgery whenever weakness persists. Peripheral
      nerve ultrasound seems to be of limited prognostic value in these
      mononeuropathies.

PMID- 23530752
TI  - Maneuvering the internal porosity and surface morphology of electrospun
      polystyrene yarns by controlling the solvent and relative humidity.
AB  - This article presents a simple and reliable method for generating polystyrene
      (PS) yarns composed of bundles of nanofibrils by using a proper combination of
      solvent and relative humidity. We elucidated the mechanism responsible for the
      formation of this new morphology by systematically investigating the molecular
      interactions among the polymer, solvent(s), and water vapor. We demonstrated that
      vapor-induced phase separation played a pivotal role in generating the yarns with
      a unique structure. Furthermore, we discovered that the low vapor pressure of N,N
      dimethylformamide (DMF) was critical to the evolution of pores in the interiors.
      On the contrary, the relatively high vapor pressure of tetrahydrofuran (THF)
      hindered the formation of interior pores but excelled in creating a rough
      surface. In all cases, our results clearly indicate that the formation of either
      internal porosity or surface roughness required the presence of water vapor, a
      nonsolvent of the polymer, at a proper level of relative humidity. The exact
      morphology or pore structure was dependent on the speed of evaporation of the
      solvent(s) (DMF, THF, and their mixtures) as well as the interdiffusion and
      penetration of the nonsolvent (water) and solvent(s). Our findings can serve as
      guidelines for the preparation of fibers with desired porosity both internally
      and externally through electrospinning.

PMID- 23530753
TI  - The characterization of a thermostable and cambialistic superoxide dismutase from
      Thermus filiformis.
AB  - The superoxide dismutase (TfSOD) gene from the extremely thermophilic bacterium
      Thermus filiformis was cloned and expressed at high levels in mesophilic host.
      The purified enzyme displayed approximately 25 kDa band in the SDS-PAGE, which
      was further confirmed as TfSOD by mass spectrometry. The TfSOD was characterized
      as a cambialistic enzyme once it had enzymatic activity with either manganese or
      iron as cofactor. TfSOD showed thermostability at 65, 70 and 80 degrees C. The
      amount of enzyme required to inhibit 50% of pyrogallol autoxidation was 0.41,
      0.56 and 13.73 mg at 65, 70 and 80 degrees C, respectively. According to the
      circular dichroism (CD) spectra data, the secondary structure was progressively
      lost after increasing the temperature above 70 degrees C. The 3-dimensional model
      of TfSOD with the predicted cofactor binding corroborated with functional and CD
      analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: This manuscript describes the
      expression and characterization of a superoxide dismutase (SOD) from Thermus
      filiformis with thermophilic and cambialistic characteristics. The SODs are among
      the most potent antioxidants known in nature, and their stability and
      pharmacokinetics can vary widely in accordance to their biological source.
      Although the currently clinical research work has been focused on human and
      bovine SODs, alternative sources may become more biotechnological attractive in
      the near future. Our study brings new insights for the research field of
      antioxidant enzymes with potential application on pharmaceutical, cosmetics and
      food formulations.

PMID- 23530754
TI  - Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone
      reader BRD4 bromodomain.
AB  - Recognizing acetyllysine of histone is a vital process of epigenetic regulation
      that is mediated by a protein module called bromodomain. To contribute novel
      scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based
      drug discovery approach. By successively applying docking and X-ray
      crystallography, we were able to identify 9 fragment hits from diffracting more
      than 60 crystals. In the present work, we described four of them and carried out
      the integrated lead optimization for fragment 8, which bears a 2-thiazolidinone
      core. After several rounds of structure guided modifications, we assessed the
      druggability of 2-thiazolidinone by modulating in vitro pharmacokinetic studies
      and cellular activity assay. The results showed that two potent compounds of 2
      thiazolidinones have good metabolic stability. Also, the cellular assay confirmed
      the activities of 2-thiazolidinones. Together, we hope the identified 2
      thiazolidinone chemotype and other fragment hits described herein can stimulate
      researchers to develop more diversified bromodomain inhibitors.

PMID- 23530755
TI  - Sevoflurane has no adverse effects on renal function in cirrhotic patients: a
      comparison with propofol.
AB  - BACKGROUND: Cirrhotic patients are prone to developing renal dysfunction after
      anaesthesia and surgery. However, no consensus has been reached whether
      sevoflurane could have adverse effects on renal function in cirrhotic patients.
      We hypothesised that the use of sevoflurane for general anaesthesia would lead to
      post-operative renal dysfunction in cirrhotic patients undergoing liver
      resection. METHODS: A total of 200 patients undergoing liver resection were
      randomly assigned to a propofol or sevoflurane group. The influence of
      sevoflurane or propofol on renal function was evaluated by the maximal change,
      the difference between the pre-operative baseline and the highest values of serum
      creatinine and blood urea nitrogen measured at day 1, 3 and 6 post-operatively.
      RESULTS: The maximal change in serum creatinine after liver resection was -4.52
      (5.78) MUmol/l and -3.37 (7.34) MUmol/l with P = 0.398, and that in blood urea
      nitrogen was 0.41 (1.49) mmol/l and 0.93 (1.54) mmol/l with P = 0.098 between the
      sevoflurane group (n = 52) and the propofol group (n = 50), respectively.
      CONCLUSIONS: Sevoflurane does not seem to impair post-operative renal function in
      cirrhotic patients undergoing liver resection.

PMID- 23530757
TI  - Magnesium sulphate for prevention of eclampsia: are intramuscular and intravenous
      regimens equivalent? A population pharmacokinetic study.
AB  - OBJECTIVE: To compare magnesium sulphate concentrations achieved by intramuscular
      and intravenous regimens used for the prevention of eclampsia. SETTING: Low
      resource obstetric hospitals in Nagpur and Vellore, India. POPULATION: Pregnant
      women at risk for eclampsia due to hypertensive disease. METHODS: A
      pharmacokinetic study was performed as part of a randomised trial that enrolled
      300 women comparing intramuscular and intravenous maintenance regimens of
      magnesium dosing. Data from 258 enrolled women were analysed in the
      pharmacokinetic study. A single sample was drawn per woman with the expectation
      of using samples in a pooled data analysis. MAIN OUTCOME MEASURES:
      Pharmacokinetic parameters of magnesium distribution and clearance. RESULTS:
      Magnesium clearance was estimated to be 48.1 dl/hour, volume of distribution to
      be 156 dl and intramuscular bioavailability to be 86.2%. The intramuscular
      regimen produced higher initial serum concentrations, consistent with a
      substantially larger loading dose. At steady state, magnesium concentrations in
      the intramuscular and intravenous groups were comparable. With either regimen, a
      substantial number of women would be expected to have serum concentrations lower
      than those generally held to be therapeutic. CONCLUSIONS: Clinical implications
      were that a larger loading dose for the intravenous regimen should be considered;
      where feasible, individualised dosing of magnesium sulphate would reduce the
      variability in serum concentrations and might result in more women with
      clinically effective magnesium concentrations; and lower dose magnesium sulphate
      regimens should be considered with caution.

PMID- 23530756
TI  - Activation of mitochondrial function and Hb expression in non-haematopoietic
      cells by an EPO inducer ameliorates ischaemic diseases in mice.
AB  - BACKGROUND AND PURPOSE: Many organs suffer from ischaemic injuries that reduce
      their ability to generate sufficient energy, which is required for functional
      maintenance and repair. Erythropoietin (EPO) ameliorates ischaemic injuries by
      pleiotropic effects. The aim of this study was to investigate the effect and
      mechanism of a small molecule EH-201, and found it as a potent EPO inducer and
      its effect in non-haematopoietic cells for therapeutic potential in ischemic
      disorders. EXPERIMENTAL APPROACH: Mice kidney slices, primary hepatocytes,
      primary cardiomyocytes and C2C12 myoblasts were treated with EH-201. The effects
      of this treatment on EPO, Hb expression and mitochondrial biogenesis were
      analysed. In vivo, doxorubicin-induced cardiomyopathic mice were treated with EH
      201. The mice were subjected to an endurance test, electrocardiography and
      echocardiography, and a histological examination of the isolated hearts was
      performed. EH-201 was also administered to cisplatin-induced nephropathic mice.
      KEY RESULTS: In non-haematopoietic cells, EH-201 was potent at inducing EPO. EH
      201 also stimulated mitochondrial biogenesis and enhanced the expression of Hb by
      a mechanism dependent on EPO-mediated signalling. In mechanistic studies, using
      EPO and EPO receptor-neutralizing antibodies, we confirmed that EH-201 enhances
      EPO-EPOR autocrine activity. EH-201 robustly increased the endurance performance
      activity of healthy and cardiomyopathic mice during hypoxic stress, enhanced
      myocardial mitochondrial biogenesis and Hb expression, and also improved cardiac
      function. EH-201 ameliorated anaemia and renal dysfunction in nephropathic mice.
      CONCLUSIONS AND IMPLICATIONS: The enhancement and recovery of cellular functions
      through the stimulation of mitochondrial activity and Hb production in non
      haematopoietic cells by an inducer of endogenous EPO has potential as a
      therapeutic strategy for ischaemic diseases.

PMID- 23530758
TI  - Does Argan oil have a moisturizing effect on the skin of postmenopausal women?

PMID- 23530759
TI  - Fish researchers meet in Middle-Earth.

PMID- 23530760
TI  - Report of the Second European Zebrafish Principal Investigator Meeting in
      Karlsruhe, Germany, March 21-24, 2012.
AB  - The second European Zebrafish Principal Investigator (PI) Meeting was held in
      March, 2012, in Karlsruhe, Germany. It brought together PIs from all over Europe
      who work with fish models such as zebrafish and medaka to discuss their latest
      results, as well as to resolve strategic issues faced by this research community.
      Scientific discussion ranged from the development of new technologies for working
      with fish models to progress in various fields of research such as injury and
      repair, disease models, and cell polarity and dynamics. This meeting also marked
      the establishment of the European Zebrafish Resource Centre (EZRC) at Karlsruhe
      that in the future will serve as an important focus and community resource for
      zebrafish- and medaka-based research.

PMID- 23530761
TI  - Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the
      human gastrointestinal tract.
AB  - The zebrafish has become increasingly popular for microbiological research. It
      has been used as an infection model for a variety of pathogens, and is also
      emerging as a tool for studying interactions between a host and its resident
      microbial communities. The mouse microbiota has been transplanted into the
      zebrafish gut, but to our knowledge, there has been no attempt to introduce a
      bacterial community derived from the human gut. We explored two methods for
      colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a
      defined anaerobic microbial community derived from a single human fecal sample.
      Both environmental exposure (static immersion) and direct microinjection into the
      gut resulted in the establishment of two species-Lactobacillus paracasei and
      Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic
      species. Of particular interest is E. limosum, which, as a strict anaerobe,
      represents a group of bacteria which until now have not been shown to colonize
      the developing zebrafish gut. Our success here indicates that further
      investigation of zebrafish as a tool for studying human gut microbial communities
      is warranted.

PMID- 23530762
TI  - A longitudinal study of end-of-life preferences of terminally-ill people who live
      alone.
AB  - As a home death seems to be the perceived ideal, terminally ill people who live
      alone are at a disadvantage in terms of their place of care and death and little
      is known about their end-of-life preferences. This study aimed at eliciting
      patient preferences for their place of care and death longitudinally at two
      points during their illness trajectory, and reporting on the extent they were
      able to achieve their place of choice or congruence between preferred and actual
      place of death. A questionnaire was administered by a researcher in the patients'
      homes during two visits, 6-12 weeks apart depending on patient prognosis. Forty
      three patients of Silver Chain Hospice Care Service in Western Australia
      participated during 2009-2010. The results indicated that preferences were in
      favour of either a home or hospice death, with more preferring home as a place of
      death rather than a place of care. However, overall congruence between preferred
      and actual place of death was between 53% and 41% dependent on whether it was
      based on first or second visit preferences respectively. This is the first
      longitudinal study to elicit the end-of-life preferences of terminally ill people
      who live alone. As home may not be the preferred location for dying for many
      patients (nearly half of the patients in this study), ability to die in the place
      of choice needs to be looked at as a possible indicator of meeting patient needs
      or as a quality measure in end-of-life care.

PMID- 23530763
TI  - Lung cancer biomarkers for the assessment of modified risk tobacco products: an
      oxidative stress perspective.
AB  - Manufacturers have developed prototype cigarettes yielding reduced levels of some
      tobacco smoke toxicants, when tested using laboratory machine smoking under
      standardised conditions. For the scientific assessment of modified risk tobacco
      products, tests that offer objective, reproducible data, which can be obtained in
      a much shorter time than the requirements of conventional epidemiology are
      needed. In this review, we consider whether biomarkers of biological effect
      related to oxidative stress can be used in this role. Based on published data,
      urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F2-isoprostanes,
      serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations
      show promise, while 4-hydroxynonenal requires further qualification.

PMID- 23530764
TI  - Poly(epsilon-caprolactone)-carbon nanotube composite scaffolds for enhanced
      cardiac differentiation of human mesenchymal stem cells.
AB  - AIM: To evaluate the efficacy of electrically conductive, biocompatible composite
      scaffolds in modulating the cardiomyogenic differentiation of human mesenchymal
      stem cells (hMSCs). MATERIALS & METHODS: Electrospun scaffolds of poly(epsilon
      caprolactone) with or without carbon nanotubes were developed to promote the in
      vitro cardiac differentiation of hMSCs. RESULTS: Results indicate that hMSC
      differentiation can be enhanced by either culturing in electrically conductive,
      carbon nanotube-containing composite scaffolds without electrical stimulation in
      the presence of 5-azacytidine, or extrinsic electrical stimulation in
      nonconductive poly(epsilon-caprolactone) scaffolds without carbon nanotube and
      azacytidine. CONCLUSION: This study suggests a first step towards improving hMSC
      cardiomyogenic differentiation for local delivery into the infarcted myocardium.

PMID- 23530765
TI  - Electron paramagnetic resonance spectroscopic study of copper hopping in doped
      bis(L-histidinato)cadmium dihydrate.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was used to study Cu(II)
      dynamic behavior in a doped biological model crystal, bis(L-histidinato)cadmium
      dihydrate, in order to gain better insight into copper site stability in
      metalloproteins. Temperature-dependent changes in the low temperature X-band EPR
      spectra became visible around 100 K and continued up to room temperature. The
      measured 298 K g-tensor (principal values: 2.17, 2.16, 2.07) and copper hyperfine
      coupling tensor (principal values: -260, -190, -37 MHz) were similar to the
      average of the 77 K tensor values pertaining to two neighboring histidine binding
      sites. The observed temperature dependence was interpreted using Anderson's
      theory of motional narrowing, where the magnetic parameters for the different
      states are averaged as the copper rapidly hops between sites. The EPR pattern was
      also found to undergo a sharp sigmoidal-shaped, temperature-dependent conversion
      between two species with a critical temperature T(c) ~ 160 K. The species below
      T(c) hops between the two low temperature site patterns, and the one above T(c)
      represents an average of the molecular spin Hamiltonian coupling tensors of the
      two 77 K sites. In addition, the low and high temperature species hop between one
      another, contributing to the dynamic averaging. Spectral simulations using this 4
      state model determined a hop rate between the two low temperature sites nu(h4) =
      4.5 * 10(8) s(-1) and between the low and high temperature states nu(h2) = 1.7 *
      10(8) s(-1) at 160 K. An Arrhenius relationship of hop rate and temperature gave
      energy barriers of DeltaE4 = 389 cm(-1) and DeltaE2 = 656 cm(-1) between the two
      low temperature sites and between the low and high temperature states,
      respectively.

PMID- 23530766
TI  - Genome-wide association study of infectious bovine keratoconjunctivitis in Angus
      cattle.
AB  - BACKGROUND: Infectious Bovine Keratoconjunctivitis (IBK) in beef cattle, commonly
      known as pinkeye, is a bacterial disease caused by Moraxellabovis. IBK is
      characterized by excessive tearing and ulceration of the cornea. Perforation of
      the cornea may also occur in severe cases. IBK is considered the most important
      ocular disease in cattle production, due to the decreased growth performance of
      infected individuals and its subsequent economic effects. IBK is an economically
      important, lowly heritable categorical disease trait. Mass selection of
      unaffected animals has not been successful at reducing disease incidence. Genome
      wide studies can determine chromosomal regions associated with IBK
      susceptibility. The objective of the study was to detect single-nucleotide
      polymorphism (SNP) markers in linkage disequilibrium (LD) with genetic variants
      associated with IBK in American Angus cattle. RESULTS: The proportion of
      phenotypic variance explained by markers was 0.06 in the whole genome analysis of
      IBK incidence classified as two, three or nine categories. Whole-genome analysis
      using any categorisation of (two, three or nine) IBK scores showed that locations
      on chromosomes 2, 12, 13 and 21 were associated with IBK disease. The genomic
      locations on chromosomes 13 and 21 overlap with QTLs associated with Bovine
      spongiform encephalopathy, clinical mastitis or somatic cell count. CONCLUSIONS:
      Results of these genome-wide analyses indicated that if the underlying genetic
      factors confer not only IBK susceptibility but also IBK severity, treating IBK
      phenotypes as a two-categorical trait can cause information loss in the genome
      wide analysis. These results help our overall understanding of the genetics of
      IBK and have the potential to provide information for future use in breeding
      schemes.

PMID- 23530767
TI  - Association of a probiotic to a Helicobacter pylori eradication regimen does not
      increase efficacy or decreases the adverse effects of the treatment: a
      prospective, randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: The treatment for the eradication of Helicobacter pylori (H. pylori)
      is complex; full effectiveness is rarely achieved and it has many adverse
      effects. In developing countries, increased resistance to antibiotics and its
      cost make eradication more difficult. Probiotics can reduce adverse effects and
      improve the infection treatment efficacy.If the first-line therapy fails a second
      line treatment using tetracycline, furazolidone and proton-pump inhibitors has
      been effective and low cost in Brazil; however it implies in a lot of adverse
      effects. The aim of this study was to minimize the adverse effects and increase
      the eradication rate applying the association of a probiotic compound to second
      line therapy regimen. METHODS: Patients with peptic ulcer or functional dyspepsia
      infected by H. pylori were randomized to treatment with the furazolidone,
      tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind
      study, patients received placebo or a probiotic compound (Lactobacillus
      acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus
      faecium) in capsules, twice a day for 30 days. A symptom questionnaire was
      administered in day zero, after completion of antibiotic therapy, after the
      probiotic use and eight weeks after the end of the treatment. Upper digestive
      endoscopy, histological assessment, rapid urease test and breath test were
      performed before and eight weeks after eradication treatment. RESULTS: One
      hundred and seven patients were enrolled: 21 men with active probiotic and 19
      with placebo plus 34 women with active probiotic and 33 with placebo comprising a
      total of 55 patients with active probiotic and 52 with placebo. Fifty-one
      patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per
      protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1%
      (p=0.49); per intention to treat, 81.8% and 79.6%, respectively (p=0.53). The
      rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2%
      with placebo (p=0.20). At 30 days, it was 44.9% and 60.4%, respectively (p=0.08).
      CONCLUSIONS: The use of this probiotic compound compared to placebo in the
      proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia
      showed no significant difference in efficacy or adverse effects. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN04714018.

PMID- 23530768
TI  - Preserved endothelium-dependent dilatation of the coronary microvasculature at
      the early phase of diabetes mellitus despite the increased oxidative stress and
      depressed cardiac mechanical function ex vivo.
AB  - BACKGROUND: There has been accumulating evidence associating diabetes mellitus
      and cardiovascular dysfunctions. However, most of the studies are focused on the
      late stages of diabetes and on the function of large arteries. This study aimed
      at characterizing the effects of the early phase of diabetes mellitus on the
      cardiac and vascular function with focus on the intact coronary microvasculature
      and the oxidative stress involved. MATERIALS AND METHODS: Zucker diabetic fatty
      rats and their lean littermates fed with standard diet A04 (Safe) were studied at
      the 11th week of age. Biochemical parameters such as glucose, insulin and
      triglycerides levels as well as their oxidative stress status were measured.
      Their hearts were perfused ex vivo according to Langendorff and their cardiac
      activity and coronary microvascular reactivity were evaluated. RESULTS: Zucker
      fatty rats already exhibited a diabetic state at this age as demonstrated by the
      elevated levels of plasma glucose, insulin, glycated hemoglobin and
      triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac
      mechanical function and coronary flow. This was accompanied by an increase in the
      overall oxidative stress of the organs. However, estimation of the active form of
      endothelial nitric oxide synthase and coronary reactivity indicated a preserved
      function of the coronary microvessels at this phase of the disease. Diabetes
      affected also the cardiac membrane phospholipid fatty acid composition by
      increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels.
      CONCLUSIONS: The presence of diabetes, even at its beginning, significantly
      increased the overall oxidative stress of the organs resulting to decreased
      cardiac mechanical activity ex vivo. However, adaptations were adopted at this
      early phase of the disease regarding the preserved coronary microvascular
      reactivity and the associated cardiac phospholipid composition in order to
      provide a certain protection to the heart.

PMID- 23530769
TI  - Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer
      testis (CT-X) antigens.
AB  - BACKGROUND: L1CAM was originally identified as an adhesion molecule involved in
      neural development. In many human carcinomas L1CAM is over-expressed and is
      associated with a bad prognosis. We previously reported that L1CAM was absent in
      the vast majority of endometrioid endometrial carcinomas (ECs) (type 1) but was
      strongly expressed in the more aggressive serous and clear-cell ECs (termed type
      2). The differential regulation of L1CAM in ECs is not well understood. Recent
      evidence suggests that it can be regulated by epigenetic mechanisms. Here we
      investigated the role of DNA-methylation of the L1CAM promoter for expression. We
      also studied the relationship to cancer testis (CT-X) antigens that co-localize
      with L1CAM on chromosome Xq28, a region that is often activated in human tumors.
      METHODS: We used EC cell lines and primary tumor tissues for our analysis. For
      expression analysis we employed RT-PCR and Western blotting. DNA-Methylation of
      the L1CAM promoter was determined after bisulfite conversation and DNA
      sequencing. Tumor tissues were examined by immunohistochemical (IHC) staining.
      RESULTS: We demonstrate that the treatment of L1CAM low/negative expressing EC
      cell lines with 5'-Azacytidine (5-AzaC) or knock-down of DNMT1 (DNA
      methyltransferase 1) as well as the HDAC (histone deacetylase) inhibitor
      Trichostatin A (TSA) up-regulated L1CAM at the mRNA and protein level. The L1CAM
      gene has two promoter regions with two distinct CpG islands. We observed that the
      expression of L1CAM correlated with hypermethylation in promoter 1 and 5-AzaC
      treatment affected the DNA-methylation pattern in this region. The CT-X antigens
      NY-ESO-1, MAGE-A3 and MAGE-A4 were also strongly up-regulated by 5-AzaC or knock
      down of DNMT1 but did not respond to treatment with TSA. Primary EC tumor tissues
      showed a variable methylation pattern of the L1CAM promoter. No striking
      differences in promoter methylation were observed between tumor areas with L1CAM
      expression and those without expression. CONCLUSIONS: L1CAM expression correlated
      with methylation of the L1CAM promoter in EC cell lines. In negative cell lines
      L1CAM expression is up-regulated by epigenetic mechanism. Although genes
      localized on Xq28 are often re-expressed by human tumors, L1CAM and CT-X antigens
      show distinct regulation in response to HADC inhibitors and 5-AzaC.

PMID- 23530770
TI  - Behaviour change for better health: nutrition, hygiene and sustainability.
AB  - As the global population grows there is a clear challenge to address the needs of
      consumers, without depleting natural resources and whilst helping to improve
      nutrition and hygiene to reduce the growth of noncommunicable diseases. For fast
      moving consumer goods companies, like Unilever, this challenge provides a clear
      opportunity to reshape its business to a model that decouples growth from a
      negative impact on natural resources and health. However, this change in the
      business model also requires a change in consumer behaviour. In acknowledgement
      of this challenge Unilever organised a symposium entitled 'Behaviour Change for
      Better Health: Nutrition, Hygiene and Sustainability'. The intention was to
      discuss how consumers can be motivated to live a more healthy and sustainable
      lifestlye in today's environment. This article summarises the main conclusions of
      the presentations given at the symposium. Three main topics were discussed. In
      the first session, key experts discussed how demographic changes - particularly
      in developing and emerging countries - imply the need for consumer behaviour
      change. The second session focused on the use of behaviour change theory to
      design, implement and evaluate interventions, and the potential role of (new or
      reformulated) products as agents of change. In the final session, key issues were
      discussed regarding the use of collaborations to increase the impact and reach,
      and to decrease the costs, of interventions. The symposium highlighted a number
      of key scientific challenges for Unilever and other parties that have set
      nutrition, hygiene and sustainability as key priorities. The key challenges
      include: adapting behaviour change approaches to cultures in developing and
      emerging economies; designing evidence-based behaviour change interventions, in
      which products can play a key role as agents of change; and scaling up behaviour
      change activities in cost-effective ways, which requires a new mindset involving
      public-private partnerships.

PMID- 23530771
TI  - Structure and substrate specificity of the pyrococcal coenzyme A disulfide
      reductases/polysulfide reductases (CoADR/Psr): implications for S(0)-based
      respiration and a sulfur-dependent antioxidant system in Pyrococcus.
AB  - FAD and NAD(P)H-dependent coenzyme A disulfide reductases/polysulfide reductases
      (CoADR/Psr) have been proposed to be important for the reduction of sulfur and
      disulfides in the sulfur-reducing anaerobic hyperthermophiles Pyrococcus
      horikoshii and Pyrococcus furiosus; however, the form(s) of sulfur that the
      enzyme actually reduces are not clear. Here we determined the structure for the
      FAD- and coenzyme A-containing holoenzyme from P. horikoshii to 2.7 A resolution
      and characterized its substrate specificity. The enzyme is relatively promiscuous
      and reduces a range of disulfide, persulfide, and polysulfide compounds. These
      results indicate that the likely in vivo substrates are NAD(P)H and di-, poly-,
      and persulfide derivatives of coenzyme A, although polysulfide itself is also
      efficiently reduced. The role of the enzyme in the reduction of elemental sulfur
      (S(8)) in situ is not, however, ruled out by these results, and the possible
      roles of this substrate are discussed. During aerobic persulfide reduction, rapid
      recycling of the persulfide substrate was observed, which is proposed to occur
      via sulfide oxidation by O(2) and/or H(2)O(2). As expected, this reaction
      disappears under anaerobic conditions and may explain observations by others that
      CoADR is not essential for S(0) respiration in Pyrococcus or Thermococcus but
      appears to participate in oxidative defense in the presence of S(0). When
      compared to the homologous Npsr enzyme from Shewanella loihica PV-4 and
      homologous enzymes known to reduce CoA disulfide, the phCoADR structure shows a
      relatively restricted substrate channel leading into the sulfur-reducing side of
      the FAD isoalloxazine ring, suggesting how this enzyme class may select for
      specific disulfide substrates.

PMID- 23530772
TI  - Characterization and application of a nose-only exposure chamber for inhalation
      delivery of liposomal drugs and nucleic acids to mice.
AB  - BACKGROUND: A small nose-only exposure chamber was evaluated for inhalation
      delivery of drug carrier systems (DCSs) to mice for the treatment of lung cancer.
      The chamber then was used for inhalation delivery of an anticancer drug,
      antisense oligonucleotides (ASO), and small interfering RNA (siRNA) directly to
      the cancerous lungs of mice. METHODS: The uniformity of particle delivery across
      the ports of the exposure chamber and stability of the DCS (liposomes) during
      continuous aerosolization by a Collison nebulizer were examined. The mean
      produced particle size by number was approximately 130 nm, and the mass median
      diameter was approximately 270 nm. The system was then used to deliver DCS
      containing doxorubicin (DOX) and ASO or siRNA targeted to multidrug resistance
      associated protein 1 (MRP1) mRNA as suppressors of cancer cell resistance. The
      retention of the drug in the lungs and the effect on tumor size were compared
      after inhalation delivery and intravenous injection in a nu/nu mouse model of
      lung cancer. RESULTS: The aerosol mass across the four inhalation ports had a
      coefficient of variation of less than 12%, and approximately 1.4% of the
      nebulized mass was available for inhalation at each port. The mean size of 130 nm
      of liposomal DCS did not change significantly during continuous 60-min
      aerosolization. For inhalation delivery of DCS with DOX+ASO/siRNA, the amount of
      drugs available for inhalation was lower compared with intravenous injection of
      DOX; however, the observed lung dose and the retention time were significantly
      higher. The delivery of DOX+ASO/siRNA via inhalation resulted in tumor volume
      reduction of more than 90%, whereas only about 40% reduction was achieved after
      intravenous injection of DOX. CONCLUSIONS: The investigated exposure system is
      suitable for inhalation delivery of complex DCS, and its use to deliver DCS
      containing anticancer drugs and resistance suppressors via inhalation offered a
      superior method for lung cancer treatment in mice compared with intravenous
      injections.

PMID- 23530773
TI  - Isolation and physiological characterization of psychrophilic denitrifying
      bacteria from permanently cold Arctic fjord sediments (Svalbard, Norway).
AB  - A large proportion of reactive nitrogen loss from polar sediments is mediated by
      denitrification, but microorganisms mediating denitrification in polar
      environments remain poorly characterized. A combined approach of most-probable
      number (MPN) enumeration, cultivation and physiological characterization was used
      to describe psychrophilic denitrifying bacterial communities in sediments of
      three Arctic fjords in Svalbard (Norway). A MPN assay showed the presence of
      10(3) -10(6) cells of psychrophilic nitrate-respiring bacteria g(-1) of sediment.
      Fifteen strains within the Proteobacteria were isolated using a systematic
      enrichment approach with organic acids as electron donors and nitrate as an
      electron acceptor. Isolates belonged to five genera, including Shewanella,
      Pseudomonas, Psychromonas (Gammaproteobacteria), Arcobacter
      (Epsilonproteobacteria) and Herminiimonas (Betaproteobacteria). All isolates were
      denitrifiers, except Shewanella, which exhibited the capacity for dissimilatory
      nitrate reduction to ammonium (DNRA). Growth from 0 to 40 degrees C demonstrated
      that all genera except Shewanella were psychrophiles with optimal growth below 15
      degrees C, and adaptation to low temperature was demonstrated as a shift from
      primarily C16:0 saturated fatty acids to C16:1 monounsaturated fatty acids at
      lower temperatures. This study provides the first targeted enrichment and
      characterization of psychrophilic denitrifying bacteria from polar sediments, and
      two genera, Arcobacter and Herminiimonas, are isolated for the first time from
      permanently cold marine sediments.

PMID- 23530776
TI  - Characterization of the structural morphology of chemically modified silica
      prepared by surface polymerization of a mixture of long and short alkyl chains
      using 13C and 29Si NMR spectroscopy.
AB  - A series of bonded phases were prepared by the chemical modification of silica
      using the surface polymerization of trifunctional and difunctional ligands, and
      the structural morphology was characterized by solid-state nuclear magnetic
      resonance (NMR) spectroscopy using cross-polarization and magic angle spinning
      (CP/MAS). Mixed-phase surfaces were prepared using mixtures of trifunctional long
      chain (C18) ligands with trifunctional and difunctional short-chain (C1) ligands,
      and these surfaces were compared to the corresponding single-phase surfaces
      consisting of only long- or short-chain ligands. For both types of mixed-phase
      surfaces, the incorporation of short chains increases the overall ligand density,
      the density of long chains, and the degree of cross-linking between ligands
      compared to that of the single-phase surface consisting exclusively of long
      chains. When the percentage of long-chain ligands in the mixture is high, a
      horizontally polymerized monolayer of chains is formed on the silica surface for
      both trifunctional and difunctional short chains. However, essentially all of the
      long chains adopt a trans conformation when trifunctional short chains are used,
      and a significant number of gauche defects are observed for the long chains when
      mixed with difunctional short chains. Furthermore, the ligands on the mixed-phase
      surface are more rigid when the short chains are trifunctional. When the
      percentage of trifunctional short chains is increased, some vertical
      polymerization occurs, caused by the molecular stacking of the highly reactive
      short chains near the surface. However, this does not preclude cross-linking
      between the ligands necessary to seal the surface, and the degree of cross
      linking is quite high, suggesting that the short chains cross-link both
      vertically, away from the surface, and horizontally, across the surface. No such
      vertical polymerization is observed for the bulkier difunctional short chains.
      For both trifunctional and difunctional short chains, the surface chains are more
      mobile, with a greater number of gauche conformations among the long chains when
      the percentage of short-chain ligands in the reaction mixture is increased.

PMID- 23530775
TI  - Immunosuppression by co-stimulatory molecules: inhibition of CD2-CD48/CD58
      interaction by peptides from CD2 to suppress progression of collagen-induced
      arthritis in mice.
AB  - Targeting co-stimulatory molecules to modulate the immune response has been shown
      to have useful therapeutic effects for autoimmune diseases. Among the co
      stimulatory molecules, CD2 and CD58 are very important in the early stages of
      generation of an immune response. Our goal was to utilize CD2-derived peptides to
      modulate protein-protein interactions between CD2 and CD58, thereby modulating
      the immune response. Several peptides were designed based on the structure of the
      CD58-binding domain of CD2 protein. Among the CD2-derived peptides, peptide 6
      from the F and C beta-strand region of CD2 protein exhibited inhibition of cell
      cell adhesion in the nanomolar concentration range. Peptide 6 was evaluated for
      its ability to bind to CD58 in Caco-2 cells and to CD48 in T cells from rodents.
      A molecular model was proposed for binding a peptide to CD58 and CD48 using
      docking studies. Furthermore, in vivo studies were carried out to evaluate the
      therapeutic ability of the peptide to modulate the immune response in the
      collagen-induced arthritis (CIA) mouse model. In vivo studies indicated that
      peptide 6 was able to suppress the progression of CIA. Evaluation of the
      antigenicity of peptides in CIA and transgenic animal models indicated that this
      peptide is not immunogenic. 

PMID- 23530777
TI  - Effect of different fruit components, aeration and cold storage at 5 degrees C on
      the germination of ascospores of Neosartorya fischeri.
AB  - Germination is the process by which a spore is transformed from a dormant state
      of metabolic activity to one of high activity. Effects of different fruit
      components, aeration and cold storage at 5 degrees C on the germination of
      ascospores of Neosartorya fischeri after heat treatment were investigated by
      measuring rate and percentage germination and outgrowth of fungal biomass. Some
      activated spores reverted back to dormancy after 12 and 24 h of storage at 5
      degrees C. Ascospores germinated easily in acetate buffers. Germination of
      ascospores was retarded in medium containing citric acid and sugars. Ascospores
      cultured under low aeration showed no signs of germination. Different food
      components and growth conditions have varying effects on germination of
      ascospores. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study can
      be used in the fruit industry to predict the effect of some fruit components on
      the germination of heat-resistant ascospores. The impact of cold storage on
      ascospores, which may be activated by heat schedules used to manufacture some
      types of fruit products, will help in determining the best storage conditions for
      enhanced shelf life to be adopted immediately after heat treatment. These
      findings also help to determine for how long a fruit juice is safe at room
      temperature after production before mycotoxin synthesis by heat-resistant fungi
      sets in.

PMID- 23530778
TI  - Total synthesis of pyoverdin D.
AB  - Pyoverdin D is an important siderophore that is used by the human pathogen
      Pseudomonas aeruginosa to import iron and gain a competitive advantage. This
      unique partially cyclic octapeptide bears four nonproteinogenic amino acids,
      including (delta)N-formyl-(delta)N-hydroxy-l-ornithine, and a catechol containing
      chiral chromophore. Here, we report the first total synthesis of pyoverdin D.

PMID- 23530779
TI  - Goal directed fluid therapy: careful with conclusions.

PMID- 23530780
TI  - The risk of congenital malformations, perinatal mortality and neonatal
      hospitalisation among pregnant women with asthma: a systematic review and meta
      analysis.
AB  - BACKGROUND: There is conflicting literature on the effect of maternal asthma on
      congenital malformations and neonatal outcomes. OBJECTIVES: This review and meta
      analysis sought to determine if maternal asthma is associated with an increased
      risk of adverse neonatal outcomes. SEARCH STRATEGY: We searched electronic
      databases for: (asthma or wheeze) and (pregnan* or perinat* or obstet*).
      SELECTION CRITERIA: Cohort studies published between 1975 and March 2012
      reporting at least one perinatal outcome of interest (congenital malformations,
      neonatal complications, perinatal mortality). DATA COLLECTION AND ANALYSIS: In
      all, 21 studies met inclusion criteria in pregnant women with and without asthma.
      Further analysis was conducted on 16 studies where asthmatic women were
      stratified by exacerbation history, corticosteroid use, bronchodilator use or
      asthma severity. MAIN RESULTS: Maternal asthma was associated with a
      significantly increased risk of congenital malformations (relative risk [RR]
      1.11, 95% confidence interval [95% CI] 1.02-1.21, I(2)  = 59.5%), cleft lip with
      or without cleft palate (RR 1.30, 95% CI 1.01-1.68, I(2)  = 65.6%), neonatal
      death (RR 1.49, 95% CI 1.11-2.00, I(2)  = 0%), and neonatal hospitalisation (RR
      1.50, 95% CI 1.03-2.20, I(2)  = 64.5%). There was no significant effect of asthma
      on major malformations (RR 1.31, 95% CI 0.57-3.02, I(2)  = 70.9%) or stillbirth
      (RR 1.06, 95% CI 0.9-1.25, I(2)  = 35%). Exacerbations and use of bronchodilators
      and inhaled corticosteroids were not associated with congenital malformation
      risk. AUTHORS' CONCLUSIONS: Despite limitations related to the observational
      nature of the primary studies, this review demonstrates a small increased risk of
      neonatal complications among pregnant women with asthma. Further investigations
      into mechanisms and potential preventive interventions to improve infant outcomes
      are required.

PMID- 23530781
TI  - Roles of cocatalysts in photocatalysis and photoelectrocatalysis.
AB  - Since the 1970s, splitting water using solar energy has been a focus of great
      attention as a possible means for converting solar energy to chemical energy in
      the form of clean and renewable hydrogen fuel. Approaches to solar water
      splitting include photocatalytic water splitting with homogeneous or
      heterogeneous photocatalysts, photoelectrochemical or photoelectrocatalytic (PEC)
      water splitting with a PEC cell, and electrolysis of water with photovoltaic
      cells coupled to electrocatalysts. Though many materials are capable of
      photocatalytically producing hydrogen and/or oxygen, the overall energy
      conversion efficiency is still low and far from practical application. This is
      mainly due to the fact that the three crucial steps for the water splitting
      reaction: solar light harvesting, charge separation and transportation, and the
      catalytic reduction and oxidation reactions, are not efficient enough or
      simultaneously. Water splitting is a thermodynamically uphill reaction, requiring
      transfer of multiple electrons, making it one of the most challenging reactions
      in chemistry. This Account describes the important roles of cocatalysts in
      photocatalytic and PEC water splitting reactions. For semiconductor-based
      photocatalytic and PEC systems, we show that loading proper cocatalysts,
      especially dual cocatalysts for reduction and oxidation, on semiconductors (as
      light harvesters) can significantly enhance the activities of photocatalytic and
      PEC water splitting reactions. Loading oxidation and/or reduction cocatalysts on
      semiconductors can facilitate oxidation and reduction reactions by providing the
      active sites/reaction sites while suppressing the charge recombination and
      reverse reactions. In a PEC water splitting system, the water oxidation and
      reduction reactions occur at opposite electrodes, so cocatalysts loaded on the
      electrode materials mainly act as active sites/reaction sites spatially separated
      as natural photosynthesis does. In both cases, the nature of the loaded
      cocatalysts and their interaction with the semiconductor through the
      interface/junction are important. The cocatalyst can provide trapping sites for
      the photogenerated charges and promote the charge separation, thus enhancing the
      quantum efficiency; the cocatalysts could improve the photostability of the
      catalysts by timely consuming of the photogenerated charges, particularly the
      holes; most importantly, the cocatalysts catalyze the reactions by lowering the
      activation energy. Our research shows that loading suitable dual cocatalysts on
      semiconductors can significantly increase the photocatalytic activities of
      hydrogen and oxygen evolution reactions, and even make the overall water
      splitting reaction possible. All of these findings suggest that dual cocatalysts
      are necessary for developing highly efficient photocatalysts for water splitting
      reactions. 

PMID- 23530782
TI  - Carbon dioxide clearance in critical care.
AB  - Lung protective ventilation limiting tidal volumes and airway pressures were
      proven to reduce mortality in patients with acute severe respiratory failure.
      Hypercapnia and hypercapnic acidosis is often noted with lung protective
      ventilation. While the protective effects of lung protective ventilation are well
      recognised, the role of hypercapnia and hypercapnic acidosis remains debatable.
      Some clinicians argue that hypercapnia and hypercapnic acidosis protect the lungs
      and may be associated with improved outcomes. To the contrary, some clinicians do
      not tolerate hypercapnic acidosis and use various techniques including
      extracorporeal carbon dioxide elimination to treat hypercapnia and acidosis. This
      review aims at defining the effects of hypercapnia and hypercapnic acidosis with
      a focus on the pros and cons of clearing carbon dioxide and the modalities that
      may enhance carbon dioxide clearance.

PMID- 23530783
TI  - The patient inflating valve in anaesthesia and resuscitation breathing systems.
AB  - Patient inflating valves combined with self-inflating bags are known to all
      anaesthetists as resuscitation devices and are familiar as components of draw
      over anaesthesia systems. Their variants are also commonplace in transfer and
      home ventilators. However, the many variations in structure and function have led
      to difficulties in their optimal use, definition and classification. After
      reviewing the relevant literature, we defined a patient inflating valve as a one
      way valve that closes an exit port to enable lung inflation, also permitting
      exhalation and spontaneous breathing, the actions being automatic. We present a
      new classification based on the mechanism of valve opening/closure; namely
      elastic recoil of a flexible flap/diaphragm, sliding spindle opened by a
      spring/magnet or a hollow balloon collapsed by external pressure. The evolution
      of these valves has been driven by the difficulties documented in critical
      incidents, which we have used along with information from modern International
      Organization for Standardization standards to identify 13 ideal properties, the
      top six of which are non-jamming, automatic, no bypass effect, no rebreathing or
      air entry at patient end, low resistance, robust and easy to service. The Ambu
      and the Laerdal valves have remained popular due to their simplicity and
      reliability. Two new alternatives, the Fenton and Diamedica valves, offer the
      benefits of location away from the patient while retaining a small functional
      dead space. They also offer the potential for greater use of hybrid continuous
      flow/draw-over systems that can operate close to atmospheric pressure. The
      reliable application of positive end-expiratory pressure/continuous positive
      airway pressure remains a challenge.

PMID- 23530784
TI  - Is suppression of apoptosis a new therapeutic target in sepsis?
AB  - Sepsis remains as a leading cause of death in critically ill patients.
      Unfortunately, there have been very few successful specific therapeutic agents
      that can significantly reduce the attributable mortality and morbidity of sepsis.
      Developing novel therapeutic strategies to improve outcomes of sepsis remains an
      important focus of ongoing research in the field of critical care medicine.
      Apoptosis has recently been identified as an important mechanism of cell death
      and evidence suggests that prevention of cell apoptosis can improve survival in
      animal models of sepsis and endotoxaemia. In this review article, we summarise
      the critical role of apoptosis of the immune cells in the pathophysiology of
      sepsis and propose that blocking cell-signaling pathways leading to apoptosis may
      present a promising specific therapy for sepsis. Various methods to inhibit
      apoptosis including the cell surface Fas receptor pathway inhibitors, caspase
      inhibitors, over-expression of anti-apoptotic genes and small interfering
      ribonucleic acid therapy are discussed.

PMID- 23530785
TI  - Interventional neuroradiological procedures-a review for anaesthetists.
AB  - Interventional neuroradiology is a rapidly expanding field, and the complexity
      and duration of these procedures makes anaesthetic support essential to their
      success. Such has been the development in this area, that the American Heart
      Association has published a scientific statement on the indications for these
      procedures. A detailed understanding of patient pathology, the technical aspects
      of the interventions and their associated risks, and the remote location in which
      they are performed are important for providing expert anaesthetic care. The aim
      of this article is to provide a description and contemporary analysis of the
      common interventional neuroradiology procedures relevant to the anaesthetist.
      This article will cover the management of intracranial aneurysms, cerebral
      vasospasm following intracranial haemorrhage, intracranial and spinal
      arteriovenous malformations, idiopathic intracranial hypertension, carotid artery
      stenting, intra-arterial thrombolysis for stroke and endovascular treatment of
      intracranial atherosclerosis. Protection from ionising radiation and acute kidney
      injury are also discussed.

PMID- 23530786
TI  - Sevoflurane alone and propofol with or without remifentanil for electroconvulsive
      therapy-a randomised, crossover study.
AB  - We compared the effectiveness of three anaesthetic regimens (propofol alone,
      propofol with remifentanil and sevoflurane alone), with respect to seizure
      duration and seizure quality in patients undergoing electroconvulsive therapy.
      Thirty-nine patients underwent a total of 234 electroconvulsive therapy
      treatments in this prospective, observer blinded, crossover study. Each patient
      received either propofol 1 mg/kg alone (Group P), propofol 0.5 mg/kg and
      remifentanil 1 ug/kg (Group R), or sevoflurane alone 6% (Group S) for their
      initial electroconvulsive therapy session. The patients subsequently received an
      alternative regimen in their next session, such as from propofol 1 mg/kg alone to
      propofol 0.5 mg/kg and remifentanil 1 ug/kg, from propofol 0.5 mg/kg and
      remifentanil 1 ug/kg to sevoflurane alone 6%, or from sevoflurane alone 6% to a
      continuing alternation between drugs at each session, until their sixth session.
      Muscle paralysis was achieved with 1 mg/kg succinylcholine. Seizure duration,
      postictal suppression index, early and midictal amplitude were recorded. The mean
      motor and electroencephalogram seizure durations were significantly longer in
      Groups P and R compared to Group S (P <0.001). The postictal suppression index
      and early and midictal amplitude values were not significantly different among
      the groups. These findings indicate that the three anaesthetic regimens had
      similar effects on seizure quality parameters, although sevoflurane was
      associated with shorter seizure durations than propofol or propofol-remifentanil.

PMID- 23530787
TI  - Effectiveness of a patient blood management data system in monitoring blood use
      in Western Australia.
AB  - The aim of this paper is to describe a linked patient blood management (PBM) data
      system and to demonstrate its usefulness by presenting the blood usage data
      obtained. Our existing datasets already collected much of the required
      information in relation to PBM. However, these datasets were not linked. A
      patient identifier was used to link the Patient Administration System with the
      Laboratory Information System. Data linkage was achieved by linking the
      Laboratory Information System with the Patient Administration System records
      where blood transfusion or laboratory result date/time fell between admission and
      discharge date/time. The two datasets were then consolidated into the PBM data
      system. Blood usage data obtained from the system showed that between August 2008
      and July 2009 there were 59,627 patient completed separations in the pilot
      hospital. Of the total transfused units, 62% were red blood cells (RBC), followed
      by fresh frozen plasma (22%), cryoprecipitate (9%) and platelets (8%). Around 50%
      of RBC transfusions were administered to patients >70 years of age. General
      medicine represented 21% of RBC usage, followed by haematology (19%),
      orthopaedics (17%) and general surgery (16%). Patients with 100 g/l pre
      transfusion haemoglobin received 9% of RBC transfusions and patients with 71-100
      g/l pre-transfusion haemoglobin received 73% of RBC transfusions. The post
      transfusion haemoglobin in RBC transfusions exceeded 100 g/l in 33% of patients.
      Databases were successfully linked to produce a powerful tool to monitor blood
      utilisation and transfusion practices within a pilot PBM program. This will
      facilitate effective targeting of PBM strategies and ongoing monitoring of their
      impact.

PMID- 23530788
TI  - Tracheostomy in the critically ill: the myth of dead space.
AB  - Benefits and advantages of tracheostomy have been vigorously debated. There is a
      lack of consensus as to whether perceived clinical improvement is attributable to
      fundamental changes in respiratory dynamics. We compare the effect of
      tracheostomy versus endotracheal tube on dead space, airway resistance and other
      lung parameters in critically ill ventilated patients. Data collected included
      patients who were admitted to surgical, burn and neurosurgical intensive care
      units at the University of North Carolina. Twenty-four intubated patients were
      included in our analysis with various aetiologies of respiratory failure.
      Tracheostomy was deemed necessary either for severe neurological devastation or
      failure to wean from the ventilator. The diameter of the endotracheal tubes
      ranged from 6-8 mm and the tracheostomy tube diameters were from 6.4-8.9 mm.
      Internal diameters between endotracheal tube and tracheostomy tubes, ventilator
      settings and sedation were kept consistent throughout the study. Respiratory
      parameters were measured using the Respironics' non-invasive cardiac output 2
      device (Phillips, Andover, MA) immediately prior to tracheostomy and repeated
      within 24 hours of tracheostomy. Only two (8%) of the patients had slight
      improvement (>6% decrease in dead space). The average dead space of endotracheal
      versus tracheostomy tubes was 41+/-12.6% and 40+/-14.6%, respectively (P=0.75).
      The remaining 22 patients (92%) had no significant change in dead space,
      compliance or other respiratory parameters. This study shows that there is no
      significant difference in respiratory mechanics and dead space with a
      tracheostomy versus endotracheal tube.

PMID- 23530789
TI  - Pain relief and opioid requirements in the first 24 hours after surgery in
      patients taking buprenorphine and methadone opioid substitution therapy.
AB  - The number of patients in buprenorphine opioid substitution therapy (BOST) or
      methadone opioid substitution therapy (MOST) programs is increasing. If these
      patients require surgery, it is generally agreed that methadone should be
      continued perioperatively. While some also recommend that buprenorphine is
      continued, concerns that it may limit the analgesic effectiveness of full mu
      opioid agonists have led others to suggest that it should cease before surgery.
      However, no good evidence exists for either course of action. Therefore, we
      undertook a retrospective cohort study comparing pain relief and opioid
      requirements in the first 24 hours after surgery in 22 BOST and 29 MOST patients
      prescribed patient-controlled analgesia. There were no significant differences in
      pain scores (rest and movement), incidence of nausea or vomiting requiring
      treatment, or sedation between the BOST and MOST patient groups overall, or
      between those patients within each of these groups who had and had not received
      their methadone or buprenorphine the day after surgery. There were also no
      significant differences in patient-controlled analgesia requirements between BOST
      and MOST patient groups overall, or between patients who did or did not receive
      MOST on the day after surgery. BOST patients who were not given their usual
      buprenorphine the day after surgery used significantly more patient-controlled
      analgesia opioid (P=0.02) compared with those who had received their dose. These
      results confirm that continuation of buprenorphine perioperatively is
      appropriate.

PMID- 23530790
TI  - Eosinopenia as a predictor of unexpected re-admission and mortality after
      intensive care unit discharge.
AB  - Predicting unexpected intensive care unit (ICU) re-admission and mortality after
      critical illness is difficult. This study assessed the associations between
      eosinopenia on the day of ICU discharge and outcomes after critical illness. This
      retrospective cohort study involved a total of 1446 critically ill patients who
      survived their first ICU admission between January 2009 and March 2010 in a
      multidisciplinary ICU in Western Australia. Eosinopenia was defined as eosinophil
      count <0.01*109/l and the date of censor for survival was 31 October 2011. Of the
      1446 patients included in the study, 106 patients (7.3%) were re-admitted to the
      ICU during the same hospitalisation and 178 patients died (12.3%) after ICU
      discharge. Eosinopenia at ICU discharge occurred in 130 patients (9.7%) and was
      more common among those who were subsequently re-admitted (18.6 vs 8.6%) or died
      after ICU discharge (22.5 vs 7.5%). Eosinopenia remained associated with ICU re
      admission (odds ratio 2.50, 95% confidence interval 1.38-4.50; P=0.002) and post
      ICU mortality (hazard ratio 2.65, 95% confidence interval 1.77-3.98; P=0.001)
      after adjusting for age, gender, nocturnal discharge, neutrophil count at ICU
      discharge, elective surgical admission, Sequential Organ Failure Assessment
      scores, Acute Physiology and Chronic Health Evaluation II predicted mortality and
      chronic medical diseases. Eosinopenia at ICU discharge explained about 8.4% of
      the variability and was the third most important factor in explaining the
      variability in survival after ICU discharge. In summary, eosinopenia at ICU
      discharge was associated with an increased risk of unexpected ICU re-admission
      and post-ICU mortality.

PMID- 23530791
TI  - Simulation training for rare medications in the intensive care unit-a study with
      bivalirudin.
AB  - The purpose of this study was to assess whether simulation training can improve
      the clinician's ability to predict the effect of bivalirudin infusion. Six
      clinicians with experience using bivalirudin and six without experience (Groups
      Exp and NoExp) entered predictions for partial thromboplastin time while viewing
      a running display of clinical data obtained retrospectively from intensive care
      unit patients who had received bivalirudin infusion after cardiac surgery. All
      clinicians entered guesses for the same sequence of 30 patients. Average guessing
      errors were analysed using analysis of variance and linear regression. All
      physicians evaluated 30 patients (813 partial thromboplastin time guesses
      overall) in less than two hours. Average errors in Groups Exp and NoExp decreased
      from 9.4 and 11.7 seconds in the first tercile, to 8.2 and 8.4 seconds in the
      last tercile of patients, respectively. The guessing-errors of Group NoExp were
      significantly higher than Group Exp in the first and second terciles, with no
      significant difference in the third tercile. Linear regression indicated a
      significantly steeper learning curve in Group NoExp than Exp. Brief simulation
      training using retrospective patient data improved the ability of inexperienced
      clinicians to predict the effect of bivalirudin as compared to experienced
      clinicians.

PMID- 23530792
TI  - Patient recollections of perioperative anaesthesia risks.
AB  - There is widespread variation as to the method of presentation of informed
      anaesthetic consent with little empirical data on the nature of communication and
      how much information is retained. At a dedicated anaesthesia pre-admission
      clinic, 149 patients undergoing elective surgery under general anaesthesia were
      both verbally informed and shown written information about four major and three
      minor anaesthesia risks. The major risks were death, pneumonia, heart attack and
      stroke. The minor risks were dental damage, nausea and vomiting. On the day of
      scheduled surgery, retention of information about these anaesthetic risks was
      examined. Thirty-eight patients (26%) could not recall any anaesthesia risks, 55
      patients (37%) could not recall any major risks and 126 patients (84%) could not
      recall any minor risks. Our findings indicate that patients should receive a
      second explanation on the day of surgery, even if informed consent was provided
      only two weeks earlier.

PMID- 23530793
TI  - Spontaneous coronary artery dissection in pregnancy requiring emergency caesarean
      delivery followed by coronary artery bypass grafting.
AB  - Spontaneous coronary artery dissection is a rare and often fatal condition of
      pregnancy. The long-term morbidity is unknown, but a small cohort of patients
      develop severe ventricular dysfunction as a consequence. We describe a 37-week
      gestation parturient who presented with cardiogenic shock secondary to
      spontaneous left main coronary artery dissection. Despite rapid diagnosis,
      stabilisation with an intra-aortic balloon pump and prompt transfer to a tertiary
      centre for emergency caesarean delivery and coronary artery bypass grafting, the
      patient developed a severe postoperative dilated ischaemic cardiomyopathy. There
      is little information about the long-term outcomes and the specific anaesthesia
      management of combined emergency caesarean delivery and cardiac surgery in
      pregnancy for spontaneous coronary artery dissection. Therefore, we outline our
      multidisciplinary management of this critically ill pregnant woman.

PMID- 23530794
TI  - Differentiating athlete's heart from inherited cardiac pathology: the challenge
      of repolarisation abnormalities presenting during anaesthesia.
AB  - This case report describes an asymptomatic healthy male professional athlete who
      underwent general anaesthesia for a routine orthopaedic operation. Peri
      procedure, pronounced ST elevation suggestive of myocardial ischaemia manifested
      on the electrocardiogram lasting for four hours post-procedure, upon which the
      athlete developed deep and diffuse inferolateral T-wave inversion. These changes
      resolved spontaneously and the patient remained clinically stable throughout.
      This case demonstrates the clinical conundrum facing anaesthetists attempting to
      differentiate between repolarisation anomalies that are commonly observed in high
      level athletes and those of inherited cardiac pathology, namely hypertrophic
      cardiomyopathy, which is the leading cause of sudden cardiac death in young
      athletes.

PMID- 23530795
TI  - The use of contrast-enhanced ultrasonography in the ICU for exclusion of active
      bleeding and detection of regional perfusion impairment in a transplanted liver.

PMID- 23530796
TI  - Acute respiratory distress syndrome with refractory hypoxaemia and severe septic
      shock caused by melioidosis: successful treatment with veno-venous extracorporeal
      membrane oxygenation.

PMID- 23530797
TI  - Management of near fatal mixed tricyclic antidepressant and selective serotonin
      reuptake inhibitor overdose with Intralipid(r)20% emulsion.

PMID- 23530798
TI  - An unusual cause of respiratory distress in the neurosurgical intensive care
      unit.

PMID- 23530799
TI  - Klebsiella oxytoca outbreak in an intensive care unit: a probable link to common
      insulin vial use.

PMID- 23530800
TI  - An alternative method of transverse in-plane ultrasound-guided thoracic
      paravertebral blockade.

PMID- 23530801
TI  - Controversies in stress ulcer bleeding prophylaxis arise from differences in the
      quality of the evidence.

PMID- 23530802
TI  - General anaesthesia in a recent heart transplant recipient for endovascular
      aortic aneurysm repair.

PMID- 23530803
TI  - Documentation of regional anaesthesia for caesarean delivery.

PMID- 23530804
TI  - Tetanus in a patient with a maggot-colonised head tumor.

PMID- 23530805
TI  - The use of videolaryngoscopy for the emergency removal of hypopharyngeal foreign
      bodies.

PMID- 23530806
TI  - Antiretroviral therapy: effects on orofacial health and health care.
AB  - This study summarizes the adverse effects of antiretroviral therapy (ART) agents
      against HIV on orofacial health and health care. Current antiretroviral agents
      fall mainly into three major classes: nucleoside reverse-transcriptase inhibitors
      (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease
      inhibitors (PIs) - now with the new classes of fusion inhibitors, entry
      inhibitors--CCR5 co-receptor antagonists and HIV integrase strand transfer
      inhibitors. Many of the ART agents can have adverse orofacial effects, or can
      give rise to allergies or drug interactions--the optimum anti-HIV drug has yet to
      be found. There are few orofacial adverse effects that characterize a particular
      ART class, but erythema multiforme (EM), ulcers and xerostomia may be associated
      with reverse-transcriptase inhibitors (RTI); parotid lipomatosis, taste
      disturbance, xerostomia and perioral paraesthesia mainly related to PIs. Facial
      lipoatrophy is a common adverse effect of NRTIs; EM is more frequently associated
      with NNRTIs. Thus, although most of the more recent ART drugs and combinations of
      them show improved safety profiles, some may give rise to orofacial adverse
      effects, and may affect oral health care.

PMID- 23530808
TI  - Molecular and phenotypic characterization of methicillin-resistant Staphylococcus
      aureus from surgical site infections.
AB  - BACKGROUND: Nosocomial infections represent an important problem for the health
      of hospitalized patients. Peri-operative infections--those occurring during
      surgery or in the post-operative period--account for 15%-20% of cases. Most
      surgical site infections (SSIs) are caused by endogenous gram-positive
      microorganisms, in particular, Staphylococcus aureus, S. epidermidis, and other
      coagulase-negative staphylococci that are part of the flora of the skin. METHODS:
      A retrospective study was conducted from January 2006 to December 2010 to
      describe the epidemiology of methicillin-resistant S. aureus (MRSA) in SSIs. The
      MRSA isolates were analyzed by a combination of two genotyping methods: SCCmec
      and pulsed-field gel electrophoresis (PFGE). Also, biofilm-forming ability was
      analyzed for all isolates as an indicator of their ability to persist despite
      antibiotic treatment. RESULTS: During the study period, 1,793 swabs from SSIs
      were analyzed, and S. aureus was identified in 318/987 positive specimens (32%).
      Methicillin resistance was observed in 10% of the S. aureus isolates (n=33).
      Analysis by PFGE revealed that isolates with the same SCCmec type were unrelated.
      Instead, biofilm-forming ability tests showed that SCCmec type I MRSA had the
      highest ability to form a film. CONCLUSIONS: The strains analyzed in our study
      showed a homogeneous pattern of SCCmec type. The difference in ability to produce
      biofilm between strains of SCCmec type I and isolates with other SCCmecs was
      substantial. This virulence factor could have critical implications for the
      formation and persistence of chronic SSIs.

PMID- 23530807
TI  - Derivation and validation of a simple clinical bedside score (ATLAS) for
      Clostridium difficile infection which predicts response to therapy.
AB  - BACKGROUND: Clostridium difficile infection (CDI) continues to be a frequent and
      potentially severe infection. There is currently no validated clinical tool for
      use at the time of CDI diagnosis to categorize patients in order to predict
      response to therapy. METHODS: Six clinical and laboratory variables, measured at
      the time of CDI diagnosis, were combined in order to assess their correlation
      with treatment response in a large CDI clinical trial database (derivation
      cohort). The final categorization scheme was chosen in order to maximize the
      number of categories (discrimination) while maintaining a high correlation with
      clinical cure assessed two days after the end of therapy. Validation of the
      derived scoring scheme was done on a second large CDI clinical trial database
      (validation cohort). A third comparison was done on the two pooled databases
      (pooled cohort). RESULTS: In the derivation cohort, the best discrimination and
      correlation with cure was seen with a five-component ATLAS score (age, treatment
      with systemic antibiotics, leukocyte count, albumin and serum creatinine as a
      measure of renal function), which divided CDI patients into 11 groups (scores of
      0 to 10 inclusive) and was highly correlated with treatment outcome (R(2) = 0.95;
      P<0.001). This scheme showed excellent prediction of cure in the validation
      cohort (overall Kappa = 95.2%; P<0.0001), as well as in the pooled cohort,
      regardless of treatment (fidaxomicin or vancomycin). CONCLUSIONS: A combination
      of five simple and commonly available clinical and laboratory variables measured
      at the time of CDI diagnosis, combined into a scoring system (ATLAS), are able to
      accurately predict treatment response to CDI therapy. The ATLAS scoring system
      may be useful in stratifying CDI patients so that appropriate therapies can be
      chosen to maximize cure rates, as well as for categorization of patients in CDI
      therapeutic studies in order allow comparisons of patient groups.

PMID- 23530809
TI  - Guidelines for antibiotic prophylaxis of cholecystectomies in Norwegian
      hospitals.
AB  - BACKGROUND: Antibiotic resistance is a global problem that affects the surgical
      patient population. Guidelines for antibiotic use have been shown to be effective
      both in terms of protecting individuals undergoing surgery and ensuring
      appropriate prescribing. More than 5,000 cholecystectomies are performed each
      year in Norway. However, there are no national guidelines for prophylactic
      antibiotics. The aim of this study was to chart the existence of local guidelines
      and whether they were updated and used. This was in order to inform practice and
      contribute to a rational approach to antibiotic prophylaxis for
      cholecystectomies. METHODS: An online questionnaire was sent to consultant
      surgeons from every hospital conducting cholecystectomies in Norway. Questions
      were related to the existence, content, and evaluation of any guidelines
      concerning prophylactic antibiotic treatment. RESULTS: Thirty-seven of 47
      hospitals responded. Overall, 17 of 37 had written guidelines, although this was
      higher in university hospitals (71%) than in local ones (39%). Not all hospitals
      with guidelines had them for both laparoscopic and open surgical methods. Most
      hospitals gave prophylaxis to patients undergoing open cholecystectomies.
      Guidelines for laparoscopic patients advised no prophylaxis in six institutions,
      four hospitals recommended prophylaxis of all their patients and others
      restricted their use to specific subpopulations. The majority with guidelines had
      revised their information within the last five years. CONCLUSIONS: The presence
      and contents of guidelines vary greatly among Norwegian hospitals. Although many
      used guidelines to highlight at-risk patients needing antibiotics, there were
      cases that advocated antibiotics to patients where the benefit is doubtful. We
      recommend the establishment of a national protocol to optimize antibiotic use,
      raise awareness of resistance, and promote the treatment of patients at high risk
      of developing a health care-associated infection.

PMID- 23530810
TI  - Recovering directed networks in neuroimaging datasets using partially conditioned
      Granger causality.
AB  - Recovering directed pathways of information transfer between brain areas is an
      important issue in neuroscience and helps to shed light on the brain function in
      several physiological and cognitive states. Granger causality (GC) analysis is a
      valuable tool to detect directed dynamical connectivity, and it is being
      increasingly used. Unfortunately, this approach encounters some limitations in
      particularly when applied to neuroimaging datasets, often consisting in short and
      noisy data and for which redundancy plays an important role. In this article, we
      address one of these limitations, namely, the computational and conceptual
      problems arising when conditional GC, necessary to disambiguate direct and
      mediated influences, is used on short and noisy datasets of many variables, as it
      is typically the case in some electroencephalography (EEG) protocols and in
      functional magnetic resonance imaging (fMRI). We show that considering GC in the
      framework of information theory we can limit the conditioning to a limited number
      of variables chosen as the most informative, obtaining more stable and reliable
      results both in EEG and fMRI data.

PMID- 23530811
TI  - Increased number of astrocytes and macrophages/microglial cells in the corpus
      callosum in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      characterized by degeneration of both upper and lower motor neurons.
      Neuropathologically, degeneration of the corticospinal tracts is evident and may
      be associated with loss of motor neurons in the motor cortex. The data from a
      recently developed imaging technology, the diffusion tensor imaging method of MRI
      have suggested that white matter in the corpus callosum (CC) is lost in patients
      with ALS. However, the specific neuropathologic changes of the commissural fibers
      remain unclear. To investigate the pathologic changes of the CC in ALS, we
      analyzed midsagittal sections of the CC from eight individuals with ALS and eight
      controls by using conventional staining and immunohistochemistry with antibodies
      against CD68, GFAP and phosphorylated neurofilament (SMI-31). The CC was divided
      into seven areas. The number of CD68-immunoreactive macrophages/microglia and
      GFAP-immunoreactive astrocytes was significantly higher in individuals with ALS
      than in controls in all areas of the CC except the rostrum. Among the patients
      with ALS, the number of macrophages/microglia and astrocytes was significantly
      higher in the posterior midbody and isthmus than in the rostrum. There was no
      significant difference in number of SMI-31 immunoreactive axons between ALS and
      control group as well as among each area of the CC. These findings suggest that
      pathologic changes in the CC in ALS are present in the posterior midbody and
      isthmus, where callosal motor fibers may traverse between the two hemispheres.
      CD68 and GFAP immunohistochemistry are sensitive methods to detect those
      pathologic changes in routine paraffin-embedded specimens. 

PMID- 23530812
TI  - Treatment preferences of deep carious lesions in mature teeth: Questionnaire
      study among dentists in Northern Norway.
AB  - OBJECTIVE: To investigate preferred treatment methods of deep carious lesions in
      mature permanent teeth among dentists in Northern Norway. MATERIALS AND METHODS:
      The survey included all 437 general dental practitioners in Northern Norway
      working in the private or the public dental health service. The participants
      received an invitation with a radiograph and a clinical picture of a deep carious
      lesion in a mature permanent tooth and a questionnaire asking about demographic
      characteristics and their preferred treatment methods related to different
      clinical deep caries diagnoses. RESULTS: The response rate was 56%. There was an
      over-representation of publicly employed dentists among the respondents;
      otherwise no systematic bias related to non-responders was detected. In the
      absence of carious exposure and no symptoms, total caries excavation was the
      preferred treatment method (49%) followed by stepwise excavation (45%). In cases
      of deep caries and no exposure with symptoms, the preferences were equally
      distributed between root canal treatment (39%) and stepwise excavation (38%). In
      the presence of carious exposure but no symptoms, the preferred treatment method
      was direct pulp capping (51%) and in carious exposure with symptoms root canal
      treatment was the preferred treatment method (91%). CONCLUSIONS: There is no
      uniform treatment method of deep carious lesions among dentists in Northern
      Norway.

PMID- 23530813
TI  - Overjet, overbite and dental midline shift as predictors of tooth size
      discrepancy in a Bangladeshi population and a graphical overview of global tooth
      size ratios.
AB  - OBJECTIVES: This study aimed to measure and compare tooth size ratios in a
      Bangladeshi population across the following groups: those with normal occlusion,
      crowding or spacing; those with normal, increased or decreased overjet; those
      with normal, increased or decreased overbite; those with or without dental mid
      line discrepancy; and those with or without lip competence. It also presents a
      graphical overview of the anterior and overall ratios from the study and using
      available global data. MATERIALS AND METHODS: This study was performed on dental
      casts of 260 Bangladeshi individuals, comprising 114 males and 146 females (age
      range, 18-24 years, mean age = 20). The Bolton anterior ratio and overall ratio
      were determined for the following groups: those with normal occlusion, crowding
      or spacing; those with normal, increased or decreased overjet; those with normal,
      increased or decreased overbite; those with or without dental mid-line
      discrepancy; and those with or without lip competence. RESULTS: There were
      statistically significant differences in the anterior tooth size ratios between
      those with or without dental mid-line discrepancy, with a mean value of 78.83%
      and 80.05%, respectively. Statistically significant differences were also found
      in overall tooth size ratios between those with normal, increased or decreased
      overjet and also between those with normal, increased or decreased overbite.
      Graphical presentations of anterior and overall ratios from the present study and
      using global data showed variations between populations. CONCLUSION: In the
      Bangladeshi population, increased tooth size ratios in subjects with dental mid
      line discrepancy (anterior ratio) and also in those with decreased overjet or
      decreased overbite (overall ratio) may be predictors of tooth size discrepancies.
      The graphical overview also suggests that different international ethnic groups
      display unique Bolton ratios.

PMID- 23530815
TI  - Multitarget global sensitivity analysis of n-butanol combustion.
AB  - A model for the combustion of butanol is studied using a recently developed
      theoretical method for the systematic improvement of the kinetic mechanism. The
      butanol mechanism includes 1446 reactions, and we demonstrate that it is
      straightforward and computationally feasible to implement a full global
      sensitivity analysis incorporating all the reactions. In addition, we extend our
      previous analysis of ignition-delay targets to include species targets. The
      combination of species and ignition targets leads to multitarget global
      sensitivity analysis, which allows for a more complete mechanism validation
      procedure than we previously implemented. The inclusion of species sensitivity
      analysis allows for a direct comparison between reaction pathway analysis and
      global sensitivity analysis.

PMID- 23530814
TI  - Limited plasticity in the phenotypic variance-covariance matrix for male
      advertisement calls in the black field cricket, Teleogryllus commodus.
AB  - Phenotypic integration and plasticity are central to our understanding of how
      complex phenotypic traits evolve. Evolutionary change in complex quantitative
      traits can be predicted using the multivariate breeders' equation, but such
      predictions are only accurate if the matrices involved are stable over
      evolutionary time. Recent study, however, suggests that these matrices are
      temporally plastic, spatially variable and themselves evolvable. The data
      available on phenotypic variance-covariance matrix (P) stability are sparse, and
      largely focused on morphological traits. Here, we compared P for the structure of
      the complex sexual advertisement call of six divergent allopatric populations of
      the Australian black field cricket, Teleogryllus commodus. We measured a subset
      of calls from wild-caught crickets from each of the populations and then a second
      subset after rearing crickets under common-garden conditions for three
      generations. In a second experiment, crickets from each population were reared in
      the laboratory on high- and low-nutrient diets and their calls recorded. In both
      experiments, we estimated P for call traits and used multiple methods to compare
      them statistically (Flury hierarchy, geometric subspace comparisons and random
      skewers). Despite considerable variation in means and variances of individual
      call traits, the structure of P was largely conserved among populations, across
      generations and between our rearing diets. Our finding that P remains largely
      stable, among populations and between environmental conditions, suggests that
      selection has preserved the structure of call traits in order that they can
      function as an integrated unit.

PMID- 23530816
TI  - Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc(-/+)
      mice.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of death from
      cancer in the United States. Colorectal cancers have a prolonged latency
      following initiation that may span decades providing ample time for implementing
      a chemoprevention strategy that could block or reverse the progression to CRC.
      Cdk4 pathway alterations have been linked to a number of cancers including CRC.
      In these experiments we focused on the Cdk4 pathway and its role in intestinal
      tumorigenesis as a possible target in chemoprevention strategies. METHODS: We
      evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor
      formation by crossing Cdk4(-/-) mice to Apc(-/+) mice. In addition, we tested the
      effect of the dietary compound silibinin on the Cdk4 pathway in Apc(-/+) mice and
      HT-29 colon cancer cells in culture. RESULTS: Cdk4(-/-) mice backcrossed to Apc(
      /+) mice reduced intestinal adenoma formation compared to Apc(-/+) controls.
      Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of
      the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a
      result silibinin blocked the development of intestinal adenomas by 52% in this
      genetic model (Apc(-/+) mice) of early events in colorectal cancer formation. No
      toxic abnormalities were detected in mice which received silibinin. CONCLUSIONS:
      Modification of the Cdk4 pathway using a natural plant-derived compound such as
      silibinin may be a useful chemopreventive strategy for colorectal carcinomas.

PMID- 23530817
TI  - InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in
      European adult patients--the LIAISON study protocol.
AB  - BACKGROUND: According to international guidelines, the goal of asthma management
      is to achieve and maintain control of the disease, which can be assessed using
      composite measures. Prospective studies are required to determine how these
      measures are associated with asthma outcomes and/or future risk. The
      'InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol
      (LIAISON)' observational study has been designed to evaluate asthma control and
      its determinants, including components of asthma management. METHODS/DESIGN: The
      LIAISON study will be conducted in 12 European countries and comprises a cross
      sectional phase and a 12-month prospective phase. Both phases will aim at
      assessing asthma control (six-item Asthma Control Questionnaire, ACQ), asthma
      related quality of life (Mini Asthma Quality of Life Questionnaire, Mini-AQLQ),
      risk of non-adherence to treatment (four-item Morisky Medication Adherence Scale,
      MMAS-4), potential reasons for poor control, treatment strategies and associated
      healthcare costs.The cross-sectional phase will recruit > 8,000 adult patients
      diagnosed with asthma for at least 6 months and receiving the same asthma
      treatment in the 4 weeks before enrolment.The prospective phase will include all
      patients with uncontrolled/poorly controlled asthma at the initial visit to
      assess the proportion reaching control during follow-up and to examine predictors
      of future risk. Visits will take place after 3, 6 and 12 months. DISCUSSION: The
      LIAISON study will provide important information on the prevalence of asthma
      control and on the quality of life in a broad spectrum of real-life patient
      populations from different European countries and will also contribute to
      evaluate differences in management strategies and their impact on healthcare
      costs over 12 months of observation. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier, NCT01567280.

PMID- 23530818
TI  - Inhibition of ejaculation by the non-peptide oxytocin receptor antagonist
      GSK557296: a multi-level site of action.
AB  - BACKGROUND AND PURPOSE: Oxytocin (OT) plays a major role in the control of male
      sexual responses. Notably, blockade of OT receptors has been reported to inhibit
      ejaculation in animals. The study aimed to investigate the action of a highly
      selective, non-peptide OT antagonist GSK557296 in a model of pharmacologically
      induced ejaculation in anaesthetized rats. The site of action was assessed by
      investigating different delivery routes for this compound. EXPERIMENTAL APPROACH:
      Urethane-anaesthetized Wistar rats were implanted with a cerebral ventricle
      cannula for i.c.v. injections or with a subdural catheter for intrathecal (i.t.)
      GSK557296 injections. Occurrence of ejaculation was assessed following i.v. 7
      hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT), a dopamine D3 receptor agonist.
      In addition, seminal vesicle pressures (SVP) and bulbospongiosus muscle (BS) EMG
      were recorded as physiological markers of emission and expulsion phases of
      ejaculation respectively. KEY RESULTS: Highest i.v. GSK557296 dose reduced
      occurrence of ejaculation and increases in SVP but had no effect on BS-EMG.
      I.c.v. GSK557296 dose dependently inhibited ejaculation, increases in SVP and BS
      contractions. At spinal thoracic level, GSK557296 dose dependently inhibited
      ejaculation and increases in SVP but BS-EMG was impaired only with the highest
      dose. When delivered at lumbar level, GSK557296 dose dependently inhibited
      ejaculation, increases in SVP and BS contractions. CONCLUSIONS AND IMPLICATIONS:
      In the 7-OH-DPAT-induced ejaculation model, GSK557296 acts peripherally and
      centrally to inhibit ejaculation with different modalities. Blockade of brain OT
      receptors seems to be the most effective mechanism of action. Targeting central
      OT receptors with highly selective antagonist seems a promising approach for the
      treatment of premature ejaculation.

PMID- 23530819
TI  - Mortalin - a multipotent chaperone regulating cellular processes ranging from
      viral infection to neurodegeneration.
AB  - Heat shock 70kDa protein 9 (HSPA9)/mortalin is a heat-uninducible member of the
      heat shock 70 protein family. This protein has been attributed many cellular
      functions, including energy generation, stress response, carcinogenesis and
      involvement in neurodegenerative diseases, which is well documented by many names
      it has been given (CSA, MOT, MOT2, GRP75, PBP74, GRP-75, HSPA9B, MGC4500,
      MTHSP75, and mortalin). As an immortalization marker (hence the name "mortalin")
      in mouse embryonic fibroblasts cybrids it preferentially segregated with loss of
      immortality in passaged cells. Mortalin regulates the functions of the tumor
      suppressor protein p53 and plays important roles in stress response and
      maintenance of the mitochondria and endoplasmic reticulum. Furthermore, mortalin
      appears to have roles in membrane trafficking and viral release regulation, since
      it interacts with Nef protein it is necessary for secretion of exosomal negative
      factor (Nef) and HIV-1 virus release. Recently, mortalin has been described as a
      significant player in neurodegenerative diseases. Mutations in HSPA9 gene have
      been found in Parkinson?s disease patients; mortalin isoform expression differs
      in hippocampus of patients with Alzheimer?s disease and could regulate the beta
      amyloid toxicity pathway. In this review we summarize the functions of mortalin,
      its pathological implications in neuronal dysfunction and possible roles in
      neurodegenerative diseases. KEYWORDS: HSPA9/mortalin/GRP75; mitochondria; cancer;
      Alzheimer?s disease.

PMID- 23530820
TI  - Genetic characterization of a border disease virus isolate originating from
      Slovakia.
AB  - In this study, a major part of genome of the pestivirus isolate 297 from
      Slovakia, comprising the 7195 nt-long 5?-UTR-NS3 region was sequenced and
      analyzed. Conserved cleavage sites between individual viral proteins of this
      region were determined and the number of amino acids of respective proteins was
      estimated as follows: 168 for Npro, 100 for C, 227 for Erns, 195 for E1, 373 for
      E2, 70 for p7, 453 for NS2, and 683 for NS3. Based on sequence and phylogenetic
      analysis of 5?-UTR, Npro, and E2 the isolate 297 was characterized as a border
      disease virus of genotype 3. It was found to be distinct from other BDV-3 strains
      analyzed so far, consequently forming a distinct branch within the phylogenetic
      clade. All these data expand a relatively limited knowledge of genetic properties
      of individual BDV genotypes and strains circulating in the Central Europe.

PMID- 23530821
TI  - N-glycosylation of the premembrane protein of Japanese encephalitis virus is
      critical for folding of the envelope protein and assembly of virus-like
      particles.
AB  - Premembrane (prM) and envelope (E) proteins, the major structural proteins of
      Japanese encephalitis virus (JEV) each contain single potential N-glycosylation
      site. In this study, the role of N-glycosylation of these proteins on their
      folding and activity were investigated. Three mutant prM and/or E (prM-E) genes
      lacking N-glycosylation sites were generated by site-directed mutagenesis. The
      effects of the N-glycan on folding, secretion and cytotoxicity of mutant proteins
      were determined by comparison with their wild type (wt) counterparts. Removal of
      N-glycan from the prM protein resulted in a complete misfolding of the E protein
      and failure to form virus-like particles (VLPs). A similar removal of N-glycan
      from the E protein led to a low efficiency of its folding and VLPs formation. The
      secretion and cytotoxicity of the E protein was also markedly impaired in case
      the glycosylation sites in the prM or E or both proteins were removed. These
      results suggest that the N-glycosylation of the prM protein is critical to the
      folding of the E protein, which makes it pivotal in the cytotoxicity of JEV
      particles and their production.

PMID- 23530822
TI  - Multiple amino acid mutations in viral RNA polymerase may synergistically enhance
      the transmissibility and/or virulence of the 2009 pandemic influenza (H1N1)
      virus.
AB  - Influenza viruses may change their transmissibility and virulence via single or
      multiple point mutations in the functional regions of their structural proteins.
      In this study, we compared sequences of all three subunits of viral RNA
      polymerase, i.e. PA, PB1 and PB2, of the 2009 pandemic influenza A (H1N1) virus
      isolates from different stages of the pandemic and found that the frequencies of
      three mutations, including V14I and K716Q in PA and K736G in PB1, showed a
      similar trend. Interestingly, the death rate of infected patients during the
      pandemic matched the frequency of the three mutations with a 2-months delay.
      These findings suggest that the combined mutations may have acted synergistically
      in enhancing the transmissibility and/or virulence of the 2009 pandemic virus. If
      definitely proved, this hypothesis could guide the rational design of antiviral
      therapeutics targeting the RNA polymerase of influenza viruses.

PMID- 23530823
TI  - Rasgrp2 regulates the permissiveness of NIH3T3 cells to a herpes simplex virus 1
      mutant with inactivated ICP34.5 gene.
AB  - We have previously reported that mtHSV, a herpes simplex virus 1 (HSV-1) mutant
      with an inactivated gene for beta-galactosidase, can efficiently lyse tumor but
      not normal cells. However, the mechanism of this selective oncolytic activity is
      so far unclear. In this study, using the phage display screening we identified
      the cellular protein binding to HSV-1 mutant (mtHSV) as (Ras guanyl releasing
      protein 2) Rasgrp2 which regulates the Ras signaling pathway. Rasgrp2 was found
      to bind directly to purified mtHSV as well as to mtHSV present within infected
      HeLa cells where it aggregated on the cell membrane. NIH3T3 cells were found
      nonpermissive to mtHSV but they became permissive following transformation with
      the Rasgrp2 gene. This effect was linked to the activation of the Ras-PKR
      signaling pathway. These observations indicate a key role of Rasgrp2 in the mtHSV
      infection of NIH3T3 cells and are important for the potential use of mtHSV in
      cancer therapy.

PMID- 23530824
TI  - Immune response of mice to a latency membrane protein 2 multiepitope antigen of
      Epstein-Barr virus applied as DNA vaccine and/or peptide vaccine.
AB  - To evaluate immune responses of mice to a latent membrane protein 2 (LMP2)
      multiepitope antigen of Epstein-Barr virus (EBV), four kinds of prime-boost
      strategies were applied. In group 1, mice were primed and boosted with DNA
      vaccine delivered by human papillomavirus (HPV) major capsid protein L1 on weeks
      0, 2, 4, and 6. Mice in group 2 were primed with DNA vaccine on weeks 0 and 2,
      and boosted with peptide vaccine on weeks 4 and 6. In group 3, mice were primed
      with peptide vaccine on weeks 0 and 2, and boosted with DNA vaccine on weeks 4
      and 6. Mice in group 4 were primed and boosted with DNA vaccine together with
      peptide vaccine on weeks 0, 2, 4 and 6. EBV-LMP2-specific IgG, IgG1, IgG2a, and
      IgA antibodies, and HPV L1-specific IgG antibodies were determined by ELISA.
      Cytotoxic T-lymphocytes (CTL) activity was measured by LDH release assay. The
      results of this study show that priming with DNA vaccine, and boosting with
      peptide vaccine (group 2) induced a significant humoral immune response, and also
      an effective CTL activity, which could be regarded as an optimal prime-boost
      strategy for improving the immune effects of EBV-LMP2 multiepitope antigen.

PMID- 23530825
TI  - Purification of recombinant M3 proteins of murine gammaherpesviruses 68 and 72
      expressed in Escherichia coli.
AB  - M3 proteins of 44 kDa of murine gammaherpesviruses 68 and 72 (MHV-68, MHV-72)
      were identified as herpesvirus vCKBP-3, soluble inhibitors of the host chemokine
      network providing a selective advantage for the virus by inhibiting the antiviral
      and inflammatory response during both acute and latent infection. The MHV-72 M3
      protein was found to contain a single mutation (Asp307Gly) near its chemokine
      binding domain and differ from that of MHV-68 in the ability to bind some human
      chemokines. In this study, we optimized the expression of his-tagged M3 proteins
      of MHV-68 and MHV-72 in Escherichia coli and their purification by Ni-NTA
      chromatography under both denaturing and native conditions. The integrity of the
      N-terminus of the MHV-72 M3 protein was verified by partial sequencing. The
      results showed that E. coli is useful for the preparation of native, recombinant
      M3 proteins of murine gammaherpesviruses in sufficient quantity and purity for
      further biological studies.

PMID- 23530826
TI  - Anti-neoplastic effect of avian reovirus sigma C protein on Rous sarcoma virus
      induced tumors in chicken.
AB  - This study investigated the anti-neoplastic potential of avian reovirus sigmaC
      (sigma C) protein on Rous sarcoma virus-induced fibrosarcoma in chicken. The
      recombinant vector expressing sigmaC protein was injected intra-tumorally into
      specific pathogen free chicken with fibro-sarcoma at the dose 100ug per bird,
      while control birds were mock-treated with 100ug of empty vector per bird.
      Recombinant sigmaC protein induced apoptosis in tumors of treated birds resulting
      in progressive tumor regression, while similar changes were absent in tumors of
      mock-treated controls. The sigmaC protein-induced apoptosis in tumors was
      quantified by flow cytometry and the mean level of apoptosis up to 66% was
      observed in treated tumors, whereas any significant level of apoptosis was absent
      in mock-treated controls.

PMID- 23530827
TI  - Kaposi?s sarcoma-associated herpesvirus ORF36 protein induces chromosome
      condensation and phosphorylation of histone H3.
AB  - Kaposi?s sarcoma-associated herpesvirus (KSHV) has been known as an agent causing
      Kaposi?s sarcoma, primary effusion lymphoma, and multicentric Castleman?s
      disease. In the lytic phase of the virus cycle, various viral genes are
      expressed, which causes host cell dysregulation. Among the lytic genes, viral
      protein kinase (vPK) encoded by ORF36 is a member of serine/threonine protein
      kinase (CHPK) family, which is involved in viral gene expression, viral DNA
      replication and encapsidation, and nuclear egress of virions. Recent studies have
      shown that the BGLF4 protein of Epstein-Barr virus (EBV), a member of the CHPK
      family, alters the host cell chromatin structure through phosphorylation of its
      key regulators. The role of KSHV ORF36 in cellular mitotic events, however, is
      not yet understood. In the current study, we showed that KSHV ORF36 induced
      chromosome condensation and phosphorylation of histone H3 on Ser 10, which are
      known as cellular mitosis markers. These processes have occurred in a kinase
      activity-dependent manner.

PMID- 23530828
TI  - Survey of sweetpotato viruses in China.
AB  - Ten sweetpotato viruses were surveyed in 3 major sweetpotato planting region
      (covering 11 provinces) in China from 2006 to 2010 to understand the distribution
      of sweetpotato viral diseases. Nine out of the 10 viruses were found in every
      major planting region. The most frequently detected virus in the Northern and the
      Yangtze River region was SPMSV. In the Southern region, SPVG was the most
      frequently detected virus. Compared to the results of the survey done in 1989,
      the incidences of all the viral diseases increased.

PMID- 23530829
TI  - Homonojirimycin, an alkaloid from dayflower inhibits the growth of influenza A
      virus in vitro.
AB  - We have previously examined the antiviral effects of total alkaloids from
      Commelina communis L. (TAC). Here we investigated the active constituents of TAC,
      responsible for the antiviral effect. Harman, homonojirimycin (HNJ) and 2,5
      dihydroxymethyl-3,4-dihydroxypyrrolidine were isolated from TAC by HPLC. Only HNJ
      showed strong antiviral activity against influenza A/PR/8/34 virus (H1N1) as
      measured by cytopathic effect reduction assay. The results suggest that HNJ is
      one of the active components of TAC.

PMID- 23530830
TI  - In situ functionalization and PEO coating of iron oxide nanocrystals using seeded
      emulsion polymerization.
AB  - Herein we demonstrate that seeded emulsion polymerization is a powerful tool to
      produce multiply functionalized PEO coated iron oxide nanocrystals.
      Advantageously, by simple addition of functional surfactants, functional
      monomers, or functional polymerizable linkers-solely or in combinations thereof
      during the seeded emulsion polymerization process, a broad range of in situ
      functionalized polymer-coated iron oxide nanocrystals were obtained. This was
      demonstrated by purposeful modulation of the zeta potential of encapsulated iron
      oxide nanocrystals and conjugation of a dyestuff. Successful functionalization
      was unequivocally proven by TXRF. Furthermore, the spatial position of the
      functional groups can be controlled by choosing the appropriate spacers. In
      conclusion, this methodology is highly amenable for combinatorial strategies and
      will spur rapid expedited synthesis and purposeful optimization of a broad scope
      of nanocrystals.

PMID- 23530831
TI  - Anti-inflammatory effects of triptolide improve left ventricular function in a
      rat model of diabetic cardiomyopathy.
AB  - AIMS: Given the importance of inflammation in the onset and progression of
      diabetic cardiomyopathy, we investigated the potential protective effects of
      triptolide, an anti-inflammatory agent, in streptozotocin-induced diabetic rat
      model and in H9c2 rat cardiac cells exposed to high glucose. METHODS AND RESULTS:
      Diabetic rats were treated with triptolide (100, 200, or 400 MUg/kg/day
      respectively) for 6 weeks. At the end of this study, after cardiac function
      measurements were performed, rats were sacrificed and their hearts were harvested
      for further histologic and molecular biologic analysis. Enhanced activity and
      expression of nuclear factor-kappaB (NF-kappaB) p65 in diabetic hearts were
      associated with increased inflammatory response, as demonstrated by increased pro
      inflammatory cytokines, cell adhesion molecules and invading inflammatory cells,
      as well as increased fibrosis, in line with impaired left ventricular function.
      Triptolide attenuated these morpho-functional alterations. Furthermore,
      triptolide (20 ng/ml) also attenuated high glucose-induced inflammation in H9c2
      rat cardiac cells. CONCLUSION: Our data demonstrate that anti-inflammatory
      effects of triptolide involving the NF-kappaB signaling pathway can improve left
      ventricular function under diabetic conditions, suggesting triptolide treatment
      might be beneficial in diabetic cardiomyopathy.

PMID- 23530832
TI  - Editorial: arteriovenous malformation.

PMID- 23530834
TI  - Design, synthesis, biological evaluation, and docking studies of (s)
      phenylalanine derivatives with a 2-cyanopyrrolidine moiety as potent dipeptidyl
      peptidase 4 inhibitors.
AB  - A novel series of (S)-phenylalanine derivatives with a 2-cyanopyrrolidine moiety
      were designed and synthesized through a rational drug design strategy. Biological
      evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4
      (DPP-4) inhibitors; among them, the cyclopropyl-substituted phenylalanine
      derivative 11h displayed the most potent DPP-4 inhibitory activity with an IC50
      value of 0.247 MUm. In addition, molecular docking analysis of the representative
      compounds 11h, 11k, and 15a were performed, which not only revealed the impact of
      binding modes on DPP-4 inhibitory activity but also provided additional
      methodological values for design and optimization. 

PMID- 23530833
TI  - Patterns and evolution of ACGT repeat cis-element landscape across four plant
      genomes.
AB  - BACKGROUND: Transcription factor binding is regulated by several interactions,
      primarily involving cis-element binding. These binding sites maintain specificity
      by means of their sequence, and other additional factors such as inter-motif
      distance and spacer specificity. The ACGT core sequence has been established as a
      functionally important cis-element which frequently regulates gene expression in
      synergy with other cis-elements. In this study, we used two monocotyledonous -
      Oryza sativa and Sorghum bicolor, and two dicotyledonous species - Arabidopsis
      thaliana and Glycine max to analyze the conservation of co-occurring ACGT core
      elements in plant promoters with respect to spacer distance between them. Using
      data generated from Arabidopsis thaliana and Oryza sativa, we also identified
      conserved regions across all spacers and possible conditions regulating gene
      promoters with multiple ACGT cis-elements. RESULTS: Our data indicated specific
      predominant spacer lengths between co-occurring ACGT elements, but these lengths
      were not universally conserved across all species under analysis. However, the
      frequency distribution indicated local regions of high correlation among monocots
      and dicots. Sequence specificity data clearly revealed a preference for G at the
      first and C at the terminal position of a spacer sequence, suggesting that the G
      box motif is the most prevalent for the ACGT class of promoters. Using gene
      expression databases, we also observed trends suggesting that co-occurring ACGT
      elements are responsible for gene regulation in response to exogenous stress.
      Conservation in patterns of ACGT (N) ACGT among orthologous genes also indicated
      the possibility that emergence of functional significance across species was a
      result of parallel evolution of these cis-elements. CONCLUSIONS: Although the
      importance of ACGT elements has been acknowledged for several plant species, ours
      is the first study that attempts to compare their occurrence across four species
      and analyze conservation among them. The apparent preference for particular
      spacer distances suggest that these motifs might be implicated in important
      physiological functions which are yet to be identified. Variations in correlation
      patterns among monocots and dicots might arise out of differences in
      transcriptional regulation in the two classes. In accordance with literature, we
      established the involvement of co-occurring ACGT elements in stress responses and
      showed how this regulation differs with variation in the ACGT (N) ACGT motif. We
      believe that our study will be an essential resource in determining optimum
      spacer length and spacer sequence between ACGT elements for promoter design in
      future.

PMID- 23530835
TI  - Characterization of water and wildlife strains as a subgroup of Campylobacter
      jejuni using DNA microarrays.
AB  - Campylobacter jejuni is the leading cause of human bacterial gastroenteritis
      worldwide, but source attribution of the organism is difficult. Previously, DNA
      microarrays were used to investigate isolate source, which suggested a non
      livestock source of infection. In this study we analysed the genome content of
      162 clinical, livestock and water and wildlife (WW) associated isolates combined
      with the previous study. Isolates were grouped by genotypes into nine clusters
      (C1 to C9). Multilocus sequence typing (MLST) data demonstrated that livestock
      associated clonal complexes dominated clusters C1-C6. The majority of WW isolates
      were present in the C9 cluster. Analysis of previously reported genomic variable
      regions demonstrated that these regions were linked to specific clusters. Two
      novel variable regions were identified. A six gene multiplex PCR (mPCR) assay,
      designed to effectively differentiated strains into clusters, was validated with
      30 isolates. A further five WW isolates were tested by mPCR and were assigned to
      the C7-C9 group of clusters. The predictive mPCR test could be used to indicate
      if a clinical case has come from domesticated or WW sources. Our findings provide
      further evidence that WW C. jejuni subtypes show niche adaptation and may be
      important in causing human infection. 

PMID- 23530836
TI  - Microparticle electrodes and single particle microbatteries: electrochemical and
      in situ microRaman spectroscopic studies.
AB  - Studies of the intrinsic electrochemical, structural, and electronic propertiesof
      microparticles of energy storage materials can provide much needed insight into
      the factors that control various aspects of the performance of technical
      electrodes for battery applications. This Account summarizes efforts made in our
      laboratories toward the development and implementation of methods for the in situ
      electrical, optical, and spectroscopic characterization of microparticles of a
      variety of such materials, including Ni hydroxide, Zn, carbon, and lithiated Mn
      and Co oxides. In the case of Ni hydroxide, the much darker appearance of NiOOH
      compared to the virtually translucent character of virgin Ni(OH)2 allowed for the
      spatial and temporal evolution of charge flow within spherical microparticles of
      Ni(OH)2 to be monitored in real time during the first scan toward positive
      potentials using computer-controlled video imaging. In situ Raman scattering
      measurements involving single microparticles of Zn harvested from a commercial
      Zn|MnO2 battery revealed that passive films formed in strongly alkaline solutions
      by stepping the potential from 1.55 V to either 0.7 or 0.8 V vs SCE displayed a
      largely enhanced feature at ca. 565 cm(-1) ascribed to a longitudinal optical
      phonon mode of ZnO, an effect associated with the presence of interstitial Zn and
      oxygen deficiencies in the lattice. In addition, significant amounts of
      crystalline ZnO could be detected only for passive films formed at the same two
      potentials after the electrodes had been roughened by a single passivation
      reduction step. Quantitative correlations were found in the case of LiMn2O4 and
      KS-44 graphite between the Raman spectral properties and the state of charge. In
      the case of KS-44, a chemometrics analysis of the spectroscopic data in the
      potential region in which the transition between dilute phase 1 and phase 4 of
      lithiated graphite is known to occur made it possible to determine independently
      the fraction of each of the two phases present as a function of potential without
      relying on the coulometric information. Also featured in this Account are methods
      we developed for the assembly and electrochemical characterization of Zn|MnO2 and
      nickel|metal-hydride Ni|MH alkaline batteries incorporating single microparticles
      of the active materials. As evidenced from the data collected, the voltage-time
      profiles for constant current operation for both types of devices were found to
      be similar to those of commercially available batteries involving the same
      chemistries. The ability to monitor the state of charge of individual particles
      based strictly on spectroscopic data is expected to open exciting new prospects
      for visualizing the flow of charge within electrodes in Li-ion batteries, an area
      that is being vigorously pursued in our laboratories. 

PMID- 23530837
TI  - Different ways of subcutaneous tissue and skin closure at cesarean section: a
      randomized clinical trial on the long-term cosmetic outcome.
AB  - OBJECTIVE: To study the effect of subcutaneous tissue closing and the effect of
      two different skin closure methods at cesarean section on long-term cosmetic
      results. DESIGN: Randomized controlled trial. SETTING: A large teaching hospital
      in the Netherlands. POPULATION: Women undergoing a cesarean section. METHODS:
      Women undergoing a cesarean section were assigned to subcutaneous tissue closure
      or not, and skin closure with staples or intracutaneous sutures. Operating time,
      postoperative pain and incidence of complications were recorded. Long-term
      cosmetic result was assessed 1 year postoperatively through the Patient and
      Observer Scar Assessment Scale (POSAS) and Numeric Rating Scale (NRS). MAIN
      OUTCOME MEASURES: The POSAS for subjective and objective scar rating and the NRS
      to provide an overall opinion on appearance of the scar 1 year after surgery.
      RESULTS: Of the 218 women randomized, data from 145 women could be analysed after
      1 year of follow-up. No significant differences were detected in long-term
      cosmetic outcome between the different closure methods. Except for operating
      time, no differences in other secondary outcome measures were found. CONCLUSIONS:
      At cesarean section, closing the subcutaneous tissue or not and using staples or
      intracutaneous sutures results in an equivalent long-term cosmetic appearance of
      the scar.

PMID- 23530838
TI  - Evidence for a transient peroxynitro acid in the reaction catalyzed by nitronate
      monooxygenase with propionate 3-nitronate.
AB  - Nitronate monooxygenase is a flavin-dependent enzyme that catalyzes the
      denitrification of propionate 3-nitronate (P3N) and other alkyl nitronates. The
      enzyme was previously known as 2-nitropropane dioxygenase, until its
      reclassification in 2010 by the IUBMB. Physiologically, the monooxygenase from
      fungi protects the organism from the environmental occurrence of P3N, which shuts
      down the Krebs cycle by inactivating succinate dehydrogenase and fumarase. The
      inhibition of these enzymes yields severe neurological disorders or death. Here,
      we have used for the first time steady-state and rapid kinetics, viscosity and pH
      effects, and time-resolved absorbance spectroscopy of the enzyme in turnover with
      P3N and the substrate analogue ethyl nitronate (EN) to elucidate the mechanism of
      the reaction. A transient increase in absorbance at ~300 nm, never reported
      before, was seen during steady-state turnover of the enzyme with P3N and oxygen,
      with no concomitant changes between 400 and 600 nm. The transient species was not
      detected when oxygen was absent. Anaerobic reduction of the enzyme with P3N
      yielded anionic flavosemiquinone and was fast (e.g., >=1900 s(-1)). Steady-state
      kinetics demonstrated that oxygen reacts before the release of the product of P3N
      oxidation from the enzyme. No pH effects were seen with P3N on kcat/Km,
      kcat/Koxygen, and kcat; in contrast, with EN, the kcat/Km and kcat decreased with
      increasing pH defining two plateaus and a pKa ~ 8.0. Solvent viscosity at the pH
      optima suggested product release as being partially controlling the overall rate
      of turnover with the physiological substrate and its analogue. A mechanism that
      satisfies the kinetic results is proposed.

PMID- 23530839
TI  - What to do when you suspect your patient suffers from pulmonary vasculitis?
AB  - Making a diagnosis of pulmonary vasculitis is challenging. The most common cause
      of pulmonary vasculitis is small vessel anti-neutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis. Pulmonary involvement in other forms of vasculitis
      such as large vessel vasculitis is rare. Since correct and timely diagnosis is
      pivotal to start (immunosuppressive) therapy to avoid vasculitic damage, a
      complete patient history should be obtained and a physical examination performed.
      Initial laboratory evaluation should include inflammation markers, renal and
      liver function tests, and the determination of ANCA. New developments in ANCA
      testing result in tests with excellent predictive value for the diagnosis of AAV
      related pulmonary vasculitis. Consequently, ANCA should be tested with these
      tests of the so-called second (capture ELISA) or third (anchor ELISA) generation.
      In patients who are ANCA negative, a simple algorithm is presented based on
      laboratory evaluation of autoantibodies and 18F-FDG-PET-CT scanning. Such an
      algorithm may be useful for accelerating the diagnostic process needed to make a
      diagnosis of pulmonary vasculitis, or alternatively, to quickly exclude such a
      diagnosis.

PMID- 23530841
TI  - Methods and incentives for the early diagnosis of bladder pain
      syndrome/interstitial cystitis.
AB  - INTRODUCTION: The concept of interstitial cystitis (IC) has changed dramatically
      during the last decades, eventually representing a symptom complex with varying
      contents. To include all patients with bladder pain, the umbrella term 'bladder
      pain syndrome' (BPS) has been suggested, incorporating the classic presentation
      of IC as a separate phenotype. This change of concepts has not been
      uncontroversial. Bladder pain syndrome often has a profound effect on the
      patients' quality of life. Generally, recognition of this problem complex is
      hampered by insufficient familiarity in the medical community. The correct
      diagnosis is often delayed by several years and may be preceded by multiple
      medical consultations and treatment attempts. There is no doubt that an early and
      correct diagnosis is of great significance for the patient. AREAS COVERED: In
      this article, a critical review of methods and means to approach the diagnosis is
      presented including some notes of current controversies. EXPERT OPINION: The key
      to an early diagnosis is symptom recognition. We are dealing with a heterogeneous
      concept including various phenotypes. The successful treatment requires
      understanding and expedient use of objective means, such as cystoscopy, biopsy
      and input from the multidisciplinary team. In the literature, limited evidence
      exists for the management of BPS/IC, due to heterogeneity in methodology and
      description of the syndrome(s). A more consequent use of available methods is
      desirable. For the immediate future, better understanding of the aetiology,
      pathogenesis and presentation of various BPS/IC phenotypes is indispensable.

PMID- 23530840
TI  - Advances in medical diagnosis of intra-amniotic infection.
AB  - INTRODUCTION: Intrauterine infection is a global problem and a significant
      contributor to morbidity and perinatal death. The host response to infection
      causes an inflammatory state that acts synergistically with microbial insult to
      induce preterm birth and fetal damage. Prompt and accurate diagnosis of intra
      amniotic infection in the asymptomatic stage of the disease is critical for
      improved maternal and neonatal outcomes. AREAS COVERED: This article provides an
      overview of the most recent progress, challenges, and opportunities for discovery
      and clinical implementation of various maternal serum, cervicovaginal, and
      amniotic fluid biomarkers in pregnancies complicated by intra-amniotic infection.
      EXPERT OPINION: Clinically relevant biomarkers are critical to the accurate
      diagnostic of intrauterine infection. Front-end implementation of such biomarkers
      will also translate in lower incidence of early-onset neonatal sepsis (EONS)
      which is an important determinant of neonatal morbidity and mortality associated
      with prematurity. However, of the hundreds of differentially expressed proteins,
      only few may have clinical utility and thus function as biomarkers. The small
      number of validation studies along with barriers to implementation of
      technological innovations in the clinical setting are current limitations.

PMID- 23530842
TI  - Endoscopic ultrasound in the diagnosis of pancreatic cancer.
AB  - INTRODUCTION: Cross sectional imaging is important for initial evaluation of
      pancreatic cancer, whereas endoscopic ultrasound (EUS) will often help better
      visualize, differentiate and make final tissue diagnosis. It plays an important
      role in the multi-disciplinary evaluation and staging of pancreatic cancer as
      accurate staging has significant impact on treatment decisions. AREAS COVERED:
      This review will cover the yield and utility of EUS and EUS FNA for diagnosis of
      pancreas cancer. In addition, this article reviews the utility and diagnostic
      yield of the non-invasive imaging modalities, including surface ultrasound, CT
      scan, PET CT scan and MRI. Tumor size, histology and disease processes that mimic
      pancreatic cancers will also be reviewed. EXPERT OPINION: The accurate diagnosis
      and staging of pancreatic neoplasms is essential for optimal patient management.
      Abdominal imaging with multidetector CT or MRI is the most important initial step
      in the evaluation of pancreatic cancer because they are widely available and can
      detect most masses and/or demonstrate dilated bile or pancreatic ducts indicative
      of obstruction. Endoscopic ultrasound will remain important for detecting small
      tumors, ruling out diseases that mimic adenocarcinoma and for obtaining tissue
      diagnosis with fine needle aspiration.

PMID- 23530843
TI  - Hypoxia-inducible factor-1alpha as prognostic marker.
AB  - INTRODUCTION: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a key player in the
      signaling pathway that mediates a complex and pleiotropic range of adaptive
      responses to hypoxia. It serves as cellular hypoxia sensor and plays a critical
      role in physiologic processes including glucose metabolism, iron metabolism,
      erythropoiesis, angiogenesis, cell survival and apoptosis, but also, pathologic
      processes such as carcinogenesis, progression and metastasis of many cancers.
      With the recent advent of new molecular targeted therapies, there is a growing
      need of molecular understanding of physiology and physiopathology and increased
      demand of diagnosis, prognosis and follow-up markers. AREAS COVERED: This paper
      reviews the biology of regulation of HIF-1alpha, its physiological and
      physiopathological effects. EXPERT OPINION: The authors discuss the potential
      diagnosis and the prognosis significance of HIF-1alpha that was evaluated in
      recent studies.

PMID- 23530844
TI  - Biomarkers for the diagnosis and management of Parkinson's disease.
AB  - INTRODUCTION: Parkinson's disease (PD) is the most common neurodegenerative
      disease leading to movement disorders, and is characterized neuropathologically
      by the progressive loss of dopaminergic neurons, intracellular alpha-synuclein
      deposition and the formation of Lewy bodies. The difficulty of making a
      definitive diagnosis of PD itself, as opposed to other neurodegenerative diseases
      associated with parkinsonism, is a central issue in clinical PD research.
      However, recent advances in diagnostic methods, encompassing imaging techniques,
      genetic testing and measurement of biological markers may permit earlier
      diagnosis, and thus potentially improved management of PD. AREAS COVERED: In
      addition to clinical symptoms and imaging techniques, a number of genetic and
      biological markers obtained from body fluids such as cerebrospinal fluids may
      hold promise for the early detection of PD. It is often difficult to make an
      accurate diagnosis and to distinguish PD from other diseases with features of
      parkinsonism, particularly during the early stages of the disease. In this
      regard, biomarkers which are specific for PD, in combination with observation of
      clinical symptoms, may facilitate the early diagnosis and improved management of
      PD. EXPERT OPINION: Good biomarkers for PD could be helpful for early diagnosis,
      management and tracking of disease progression. Furthermore, combined analysis
      using several kinds of biomarkers may allow the detection of preclinical PD,
      which in turn may facilitate a prevention of disease onset with the use of
      disease-modifying drugs.

PMID- 23530845
TI  - Recent advances in the diagnosis of Pneumocystis jirovecii pneumonia in HIV
      infected adults.
AB  - INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) is one of the most common
      opportunistic infections in HIV-infected adults. Although the microscopic
      demonstration of the organisms in respiratory specimens is still the golden
      standard of its diagnosis, recent advances in the diagnostic tools have been
      changing the situation. AREAS COVERED: Colonization of Pneumocystis is highly
      prevalent among the general population and could be associated with the
      transmission and development of PCP in immunocompromised individuals. Nested or
      conventional polymerase chain reaction (PCR) has a high sensitivity, detecting
      Pneumocystis DNA in induced sputum or oropharyngeal wash, but often produces
      false positives. Although quantitative real-time PCR is promising for
      discriminating colonization from PCP, the targeted DNA sequences and the cut-off
      values remain to be standardized. Serum beta-D-glucan is useful as an adjunctive
      tool for the diagnosis of PCP. High-resolution computed tomography, which
      typically shows diffuse ground-glass opacities, is informative for evaluation of
      immunocompromised patients with suspected PCP and normal chest radiography.
      EXPERT OPINION: Although these new tools have been making the diagnosis of PCP
      less invasive and more accurate, any one of them can not make a definitive
      diagnosis by itself. The diagnostic criteria based on the combination of the
      testing ought to be established.

PMID- 23530846
TI  - New development in the diagnosis of dengue infections.
AB  - INTRODUCTION: Dengue is of major concern around the world. Having no
      pathognomonic features that reliably distinguish it from other febrile illnesses,
      laboratory diagnosis is important for confirmation. Ideally, a dengue diagnostic
      test should be sensitive, specific and applicable from the onset of disease to 10
      days post-infection. AREAS COVERED: In this review, the pro and cons of currently
      available diagnostic arrays as well as evaluations that have been conducted by
      numerous groups using both in-house and commercialized kits were assessed and
      reviewed. We also probed into the challenges and hurdles of applying these assays
      worldwide. This review also glimpsed at newer technologies that may be invaluable
      in the future of dengue diagnostics. EXPERT OPINION: To diagnose dengue, an
      understanding of the complex immune responses and the clinical features of this
      disease is essential. The MAC-ELISA currently remains the assay of choice but
      needs further evaluation and confirmation. Viral RT-PCR and NS1 have gained
      interest but their inconsistencies and great variability are of concern.
      Combinations of these tests have improved sensitivity but specificity issues
      still exist. Consequently, the favorable method of diagnosing dengue currently is
      to run multiple tests or obtain a paired sample so that more than one parameter
      is detected or a rising titer is demonstrated.

PMID- 23530847
TI  - Leptin in heart failure.
AB  - INTRODUCTION: In the study of heart failure (HF), biomarkers have served as an
      important tool for diagnostic, therapeutic and prognostic assessment. Their main
      categories in the area of HF are markers of ventricular dysfunction,
      inflammation, metabolism, neurohormones, oxidative stress, myocardial injury and
      extracellular matrix remodeling. AREAS COVERED: Leptin contributes to the
      modulation of metabolism, respiratory control and inflammation, which are factors
      associated with cardiovascular disease. Serum levels of leptin in patients with
      HF have shown conflicting results in previous studies. Most studies have
      suggested that serum leptin levels may be increased in patients without cachexia.
      On the other hand, leptin levels are decreased in patients with advanced HF and
      cardiac cachexia or specific HF etiologies such as Chagas' disease. Other studies
      have showed that leptin levels were related to exercise intolerance. The only
      exception of the direct correlation of serum leptin levels with severity of CHF
      is present in CHF with cardiac cachexia, because patients with cardiac cachexia
      have plasma leptin concentrations lower than those without cardiac cachexia.
      EXPERT OPINION: These findings can make leptin an important diagnostic and
      prognostic marker for HF and be included in routine investigation of patients
      with HF.

PMID- 23530849
TI  - Effect of repeat Kasai hepatic portoenterostomy on pediatric live-donor liver
      graft for biliary atresia.
AB  - OBJECTIVES: Treatment for patients with biliary atresia is a Kasai hepatic
      portoenterostomy; however, the efficacy of repeat Kasai hepatic portoenterostomy
      is unclear. This study sought to examine the effect of a prior Kasai hepatic
      portoenterostomy, especially a repeat Kasai hepatic portoenterostomy, on the
      outcomes of living-donor liver transplant. MATERIALS AND METHODS: One hundred
      twenty-six of 170 children that underwent a living-donor liver transplant between
      May 2001, and March 2010, received a living-donor liver transplant for biliary
      atresia. These patients were divided into 2 groups according to the number of
      previous portoenterostomies: 1 (group A, n=100) or 2 or more Kasai hepatic
      portoenterostomies (group B, n=26). Portoenterostomy was performed twice in 24
      patients in group B, 3 times in 1, and 4 times in 1. Preoperative, operative
      factors, mortality, morbidity, and survival rates were examined and compared
      between groups. RESULTS: The surgical factors such as operative time, blood loss
      per weight, cold ischemia time, and weight of the native liver were significantly
      greater in group B than they were in group A. The patient survival rates were
      comparable in the 2 groups (94.5% in group A and 93.3% in group B), and the
      difference was not statistically significant. No statistically significant
      difference was observed between the groups with regard to vascular complications,
      biliary complications, and other factors including postoperative variables. Bowel
      perforation requiring surgical repair was more frequent in group B than it was in
      group A. CONCLUSIONS: Repeat Kasai hepatic portoenterostomy might have a negative
      effect on patients who undergo living-donor liver transplant for biliary atresia
      patients with potential lethal complications such as bowel perforation. More
      biliary atresia patients could have a liver transplant, with improved survival
      and better life expectancy, if they have inadequate biliary drainage after the
      initial Kasai hepatic portoenterostomy.

PMID- 23530851
TI  - Medicolegal considerations in bisphosphonate-related osteonecrosis of the jaw.

PMID- 23530852
TI  - Poststreptococcal syndrome mimicking conjunctival lymphoma.
AB  - BACKGROUND: Poststreptococcal syndrome (PSS) can be a consequence of nonpurulent
      primary infection with group A streptococci (GAS). Postreptococcal uveitis is a
      well recognized entity with quite a few descriptions in the literature, but so
      far no conjunctival involvement has been reported.The aim of the study is to
      present a rare case of postreptococcal conjunctival lesions mimicking a lymphoma.
      CASE PRESENTATION: 19-years-old Caucasian female presented with pink, nodular
      infiltrates in the right conjunctiva that occurred a few months after upper
      respiratory tract infection and tonsillectomy. Histopathological examination of
      collected lesion samples revealed inflammatory reaction with lymphocytes
      proliferation and failed to rule out a myeloma. Complementary flow-cytometry did
      not show monoclonal proliferation of lymphocytes B. During follow-up we observed
      the complete regression of conjunctival lesions after the benzyl penicillin
      treatment prescribed by ENT specialist due to elevated plasma ASO levels.
      Therefore, we suppose that those lesions must have represented a part of
      poststreptococcal syndrome. CONCLUSIONS: To conclude, this is, to the best of our
      knowledge, the first report of conjunctival involvement in the course of PSS
      related to group A streptococci.

PMID- 23530853
TI  - Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a
      brief introduction with special reference to hippocampal sclerosis and focal
      cortical dysplasia.
AB  - Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy
      with hippocampal sclerosis (mTLE-HS) and malformation of cortical development
      (MCD), including focal cortical dysplasia (FCD), are the two most frequent causes
      of drug-resistant focal epilepsies, constituting about 50% of all surgical
      pathology of epilepsy. Several distinct histological patterns have been
      historically recognized in both HS and FCD, and several studies have tried to
      perform clinicopathological correlations. However, results have been
      controversial, particularly in terms of post-surgical seizure outcome. Recently,
      the International League Against Epilepsy constituted a Task Forces of
      Neuropathology and FCD within the Commission on Diagnostic Methods, to establish
      an international consensus of histological classification of HS and FCD,
      respectively, based on agreement with the recognition of the importance of
      defining a histopathological classification system that reliably has some
      clinicopathological correlation. Such consensus classifications are likely to
      facilitate future clinicopathological studies. Meanwhile, we reviewed the
      neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of
      HS along with no HS, based on the qualitative evaluation of the distribution and
      severity of neuronal loss and gliosis within hippocampal formation, that is, HS
      type 1 (61%) equivalent to "classical" Ammon's horn sclerosis, HS type 2 (2%)
      representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis,
      and no HS (19%). Furthermore, we performed a neuropathological comparative study
      on mTLE-HS and dementia-associated HS (d-HS) in the elderly, and confirmed that
      neuropathological features differ between mTLE-HS and d-HS in the distribution of
      hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and
      their protein expression, and presence of concomitant neurodegenerative changes,
      particularly Alzheimer type and TDP-43 pathologies. These differences may
      account, at least in part, for the difference in pathogenesis and
      epileptogenicity of HS in mTLE and senile dementia. However, the etiology and
      pathogenesis of most epileptogenic lesions are yet to be elucidated. 

PMID- 23530854
TI  - Guided bone regeneration for socket preservation in molar extraction sites:
      histomorphometric and 3D computerized tomography analysis.

PMID- 23530855
TI  - Enantio- and diastereoselective synthesis of N-acetyl dihydrotetrafibricin methyl
      ester.
AB  - A highly diastereoselective synthesis of N-acetyl dihydrotetrafibricin methyl
      ester (34) is described. The synthesis features three enantioselective double
      allylboration reactions and an intramolecular hydrosilylation/Fleming-Tamao
      oxidation sequence to establish seven of the hydroxy-bearing stereocenters of 34.
      Especially noteworthy is the fragment-assembly double allyboration reaction of 2
      and 7 using reagent 3, which provides the advanced intermediate 6 with >20:1
      diastereoselectivity.

PMID- 23530856
TI  - Effect of the charge and roughness of surfaces on normal and friction forces
      measured in aqueous solutions.
AB  - We used the atomic force microscope (AFM) to determine how the roughness and
      charge on a surface affect the adhesion and friction when measured against a
      smooth surface (colloid probe) in an aqueous solution. The effect of roughness
      was investigated by coating TiO2 crystal substrates with TiO2 nano- or micro
      sized particles, where an increase in the particle size increased the RMS
      roughness of the substrate. The charge of the substrate was varied by changing
      the pH of the aqueous solution. Force-separation curves and friction-load data
      were measured for the smooth colloid probe-rough substrate systems. The adhesion
      and friction between two surfaces in solution were seen to depend on the surface
      charge and roughness. A noncharged surface gave the greatest adhesion, while a
      charged surface gave weaker adhesions. Increasing the roughness of the surface
      resulted in a stronger adhesion. The magnitude and range of the adhesions were
      not affected by the measuring velocity in the case of a noncharged substrate but
      decreased with an increasing velocity for charged surfaces. The friction was seen
      not to depend on roughness in the case of a noncharged surface. However, in the
      case of a charged surface, the friction decreased with an increased roughness for
      low loads and then showed no dependence on the surface roughness for high loads.
      The results of this experiment show that the adhesion and friction of a system
      can be decreased via the roughness and charge of the substrate and the ion types
      in the solution.

PMID- 23530857
TI  - Role of ROCK upregulation in endothelial and smooth muscle vascular functions in
      diabetic rat aorta.
AB  - BACKGROUND: The RhoA/ROCK signaling pathway mediates vascular smooth muscle
      contraction while endogenous NO induces vasodilation through its inhibition.
      Since myosin light chain phosphatase (MLCP) and eNOS are targeted by RhoA/ROCK
      upregulation then turn to lead abnormalities in vasculature, we aimed to examine
      whether less endothelial NO-production and inhibited eNOS together with an
      upregulation of RhoA/ROCK signaling pathway in thoracic aorta can play an
      important role in vascular dysfunction under hyperglycemia. METHODS: We used
      streptozotocin-injected rats, as a model of type 1 diabetes, and their lean
      controls to investigate the role of ROCK upregulation in the function of toracic
      aorta by using electrophysiological and biochemical techniques. RESULTS: The
      protein level of ROCK isoform ROCK2 was found to be 2.5-fold higher in
      endothelium-intact aortic rings of the diabetic rats compared to those of the
      controls while its level in endothelium-denuded rings was similar among these two
      groups. Phosphorylation level of eNOS in endothelium-intact rings from the
      diabetics was 50% less compared to that of the control. ROCK inhibitors, either
      Y27632 or HA1077, induced concentration-dependent relaxation with a marked left
      shift in phenylephrine pre-contracted endothelium-intact rings from either
      diabetics or high glucose incubated controls while pretreatment of these rings
      with L-NAME abolished this shift, fully. Moreover, phosphorylation levels of both
      MLCP and MLC in endothelium-denuded rings were markedly higher in the diabetics
      than the controls. CONCLUSION: We demonstrated that diabetes-induced vascular
      dysfunction can arise due to either inbition of eNOS, thereby less endothelial NO
      production, either directly or indirectly, in part, due to an upregulation of
      ROCK2 by hyperglycemia. Additionally, our data demonstrate that high
      phosphorylation levels of both MLC and MLCP in endothelium-denuded rings can be
      due to a less endothelial NO-production dependent ROCK upregulation in the smooth
      muscle cells under hyperglycemia, as well.

PMID- 23530858
TI  - Stress and stability comparison between different systems for high tibial
      osteotomies.
AB  - BACKGROUND: High tibial osteotomy (HTO) with a medial opening wedge has been used
      to treat medial compartment osteoarthritis. However, this makes the proximal
      tibia a highly unstable structure and causes plate and screws to be the
      potentials sources for mechanical failure. Consequently, proper design and use of
      the fixation device are essential to the HTO especially for overweight or full
      weight-bearing patients. METHODS: Based on the CT-based images, a tibial finite
      element model with medial opening was simulated and instrumented with one-leg and
      two-leg plate systems. The construct was subjected to physiological and surgical
      loads. Construct stresses and wedge micromotions were chosen as the comparison
      indices. RESULTS: The use of locking screws can stabilize the construct and
      decrease the implant and bone stresses. Comparatively, the two-leg design
      provides a wider load-sharing base to form a force-couple mechanism that
      effectively reduces construct stresses and wedge micromotions. However, the
      incision size, muscular stripping, and structural rigidity are the major concerns
      of using the two-leg systems. The one-leg plates behave as the fulcrum of the
      leverage system and make the wedge tip the zone of tension and thus have been
      reported to negatively affect the callus formation. CONCLUSIONS: The choice of
      the HTO plates involved the trade-off between surgical convenience, construct
      stability, and stress-shielding effect. If the stability of the medial opening is
      the major concern, the two-leg system is suggested for the patients with heavy
      load demands and greater proximal tibial size. The one-leg system with locking
      screws can be used for the majority of the patients without heavy bodyweight and
      poor bone quality.

PMID- 23530859
TI  - Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and glial
      derived neurotrophic factor enhance angiogenesis in a tissue-engineered in vitro
      model.
AB  - Skin is a major source of secretion of the neurotrophic factors nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3),
      and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory
      innervation. Beside their neuronal contribution, we hypothesized that
      neurotrophic factors also modulate the cutaneous microvascular network. First, we
      showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while
      only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human
      endothelial cells. We demonstrated that these peptides are highly potent
      angiogenic factors using a human tissue-engineered angiogenesis model. A 40% to
      80% increase in the number of capillary-like tubes was observed after the
      addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and 50 ng/mL of
      GDNF. This is the first characterization of the direct angiogenic effect of NT-3
      and GDNF. This angiogenic effect was mediated directly through binding with the
      neurotrophic factor receptors tropomyosin-receptor kinase A (TrkA), TrkB,
      GFRalpha-1 and c-ret that were all expressed by human endothelial cells, while
      this effect was blocked by addition of the Trk inhibitor K252a. Thus, if NGF,
      BDNF, NT-3, and GDNF may only moderately regulate the microvascular network in
      normal skin, they might have the potential to greatly increase angiogenesis in
      pathological situations. 

PMID- 23530860
TI  - The role of vaccination, antiorthopoxvirus drug, and social cooperativity in a
      mathematical model of smallpox control.
AB  - Considerable effort has gone into making mathematical and computer models of
      smallpox spread and control measures, typically consisting of vaccination and
      quarantine. The orally available antiorthopoxvirus drug tecovirimat has recently
      completed Phase 2 clinical trials and shows promise as a smallpox control agent.
      We constructed 2 computer simulations to explore the use of tecovirimat in
      combination with vaccination and social cooperativity to control an outbreak. Two
      scenarios were considered: (1) a homogenously mixed, deterministic simulation of
      a single metropolitan area; and (2) a stochastic network of the 50 largest US
      metropolitan areas connected by commercial air traffic. Metropolitan-level mass
      vaccination coupled with drug treatment for all individuals who develop a fever
      considerably outperforms treating only those who develop smallpox's distinctive
      rash. Incorporating mass chemoprophylaxis represents another large improvement.
      More aggressive responses are more robust to low cooperation of the population
      with public health efforts and to faster disease spread. However, even with the
      most aggressive public health intervention, an attack that initially infects
      hundreds or thousands of individuals will need to be fought in multiple cities
      across the country.

PMID- 23530861
TI  - Microsatellite and single-nucleotide polymorphisms indicate recurrent transitions
      to asexuality in a microsporidian parasite.
AB  - Assessing the mode of reproduction of microparasites remains a difficult task
      because direct evidence for sexual processes is often absent and the biological
      covariates of sex and asex are poorly known. Species with geographically
      divergent modes of reproduction offer the possibility to explore some of these
      covariates, for example, the influence of life-history traits, mode of
      transmission and life-cycle complexity. Here, we present a phylogeographical
      study of a microsporidian parasite, which allows us to relate population genetic
      structure and mode of reproduction to its geographically diverged life histories.
      We show that in microsporidians from the genus Hamiltosporidium, that use the
      cladoceran Daphnia as host, an epidemic population structure has evolved, most
      probably since the last Ice Age. We partially sequenced three housekeeping genes
      (alpha tubulin, beta tubulin and hsp70) and genotyped seven microsatellite loci
      in 51 Hamiltosporidium isolates sampled within Europe and the Middle East. We
      found two phylogenetically related asexual parasite lines, one each from
      Fennoscandia and Israel, which share the unique ability of being transmitted both
      vertically and horizontally from Daphnia to Daphnia. The sexual forms cannot
      transmit horizontally among Daphnia, but presumably have a complex life cycle
      with a second host species. In spite of the similarities between the two asexual
      lineages, a clustering analysis based on microsatellite polymorphisms shows that
      asexual Fennoscandian parasites do not share ancestry with any other
      Hamiltosporidium that we have sampled. Moreover, allele sequence divergence at
      the hsp70 locus is twice as large in Fennoscandian than in Israeli parasites. Our
      results indicate that asexual reproduction evolved twice independently, first in
      Fennoscandian and more recently in the Israeli parasites. We conclude that the
      independent origin of asexuality in these two populations is associated with the
      altered parasite mode of transmission and the underlying dynamics of host
      populations.

PMID- 23530862
TI  - Prevalence of hypoglycemia identified by intensive bedside glucose monitoring
      among hospitalized patients with diabetes mellitus ().

PMID- 23530863
TI  - Radiosurgery for patients with unruptured intracranial arteriovenous
      malformations.
AB  - OBJECT: The appropriate management of unruptured intracranial arteriovenous
      malformations (AVMs) remains controversial. In the present study, the authors
      evaluate the radiographic and clinical outcomes of radiosurgery for a large
      cohort of patients with unruptured AVMs. METHODS: From a prospective database of
      1204 cases of AVMs involving patients treated with radiosurgery at their
      institution, the authors identified 444 patients without evidence of rupture
      prior to radiosurgery. The patients' mean age was 36.9 years, and 50% were male.
      The mean AVM nidus volume was 4.2 cm(3), 13.5% of the AVMs were in a deep
      location, and 44.4% were at least Spetzler-Martin Grade III. The median
      radiosurgical prescription dose was 20 Gy. Univariate and multivariate Cox
      regression analyses were used to determine risk factors associated with
      obliteration, postradiosurgery hemorrhage, radiation-induced changes, and
      postradiosurgery cyst formation. The mean duration of radiological and clinical
      follow-up was 76 months and 86 months, respectively. RESULTS: The cumulative AVM
      obliteration rate was 62%, and the postradiosurgery annual hemorrhage rate was
      1.6%. Radiation-induced changes were symptomatic in 13.7% and permanent in 2.0%
      of patients. The statistically significant independent positive predictors of
      obliteration were no preradiosurgery embolization (p < 0.001), increased
      prescription dose (p < 0.001), single draining vein (p < 0.001), radiological
      presence of radiation-induced changes (p = 0.004), and lower Spetzler-Martin
      grade (p = 0.016). Increased volume and higher Pittsburgh radiosurgery-based AVM
      score were predictors of postradiosurgery hemorrhage in the univariate analysis
      only. Clinical deterioration occurred in 30 patients (6.8%), more commonly in
      patients with postradiosurgery hemorrhage (p = 0.018). CONCLUSIONS: Radiosurgery
      afforded a reasonable chance of obliteration of unruptured AVMs with relatively
      low rates of clinical and radiological complications.

PMID- 23530864
TI  - Methanogenic capabilities of ANME-archaea deduced from (13) C-labelling
      approaches.
AB  - Anaerobic methanotrophic archaea (ANME) are ubiquitous in marine sediments where
      sulfate dependent anaerobic oxidation of methane (AOM) occurs. Despite
      considerable progress in the understanding of AOM, physiological details are
      still widely unresolved. We investigated two distinct microbial mat samples from
      the Black Sea that were dominated by either ANME-1 or ANME-2. The (13) C lipid
      stable isotope probing (SIP) method using labelled substances, namely methane,
      bicarbonate, acetate, and methanol, was applied, and the substrate-dependent
      methanogenic capabilities were tested. Our data provide strong evidence for a
      versatile physiology of both, ANME-1 and ANME-2. Considerable methane production
      rates (MPRs) from CO2 -reduction were observed, particularly from ANME-2
      dominated samples and in the presence of methane, which supports the hypothesis
      of a co-occurrence of methanotrophy and methanogenesis in the AOM systems
      (AOM/MPR up to 2:1). The experiments also revealed strong methylotrophic
      capabilities through (13) C-assimilation from labelled methanol, which was
      independent of the presence of methane. Additionally, high MPRs from methanol
      were detected in both of the mat samples. As demonstrated by the (13) C-uptake
      into lipids, ANME-1 was found to thrive also under methane free conditions.
      Finally, C35 -isoprenoid hydrocarbons were identified as new lipid biomarkers for
      ANME-1, most likely functioning as a hydrogen sink during methanogenesis. 

PMID- 23530865
TI  - HHM motif at the CuH-site of peptidylglycine monooxygenase is a pH-dependent
      conformational switch.
AB  - Peptidylglycine monooxygenase is a copper-containing enzyme that catalyzes the
      amidation of neuropeptides hormones, the first step of which is the conversion of
      a glycine-extended pro-peptide to its alpha-hydroxyglcine intermediate. The
      enzyme contains two mononuclear Cu centers termed CuM (ligated to imidazole
      nitrogens of H242, H244 and the thioether S of M314) and CuH (ligated to
      imidazole nitrogens of H107, H108, and H172) with a Cu-Cu separation of 11 A.
      During catalysis, the M site binds oxygen and substrate, and the H site donates
      the second electron required for hydroxylation. The WT enzyme shows maximum
      catalytic activity at pH 5.8 and undergoes loss of activity at lower pHs due to a
      protonation event with a pKA of 4.6. Low pH also causes a unique structural
      transition in which a new S ligand coordinates to copper with an identical pKA,
      manifest by a large increase in Cu-S intensity in the X- ray absorption
      spectroscopy. In previous work (Bauman, A. T., Broers, B. A., Kline, C. D., and
      Blackburn, N. J. (2011) Biochemistry 50, 10819-10828), we tentatively assigned
      the new Cu-S interaction to binding of M109 to the H-site (part of an HHM
      conserved motif common to all but one member of the family). Here we follow up on
      these findings via studies on the catalytic activity, pH-activity profiles, and
      spectroscopic (electron paramagnetic resonance, XAS, and Fourier transform
      infrared) properties of a number of H-site variants, including H107A, H108A,
      H172A, and M109I. Our results establish that M109 is indeed the coordinating
      ligand and confirm the prediction that the low pH structural transition with
      associated loss of activity is abrogated when the M109 thioether is absent. The
      histidine mutants show more complex behavior, but the almost complete lack of
      activity in all three variants coupled with only minor differences in their
      spectroscopic properties suggests that unique structural elements at H are
      critical for functionality. The data suggest a more general utility for the HHM
      motif as a copper- and pH-dependent conformational switch.

PMID- 23530866
TI  - Advance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker
      in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective
      review.
AB  - BACKGROUND: Systemic inflammation has been linked with cancer development, cancer
      cachexia and poor outcome. Advanced lung cancer inflammation index (ALI) was
      developed to assess degree of systemic inflammation at the time of diagnosis in
      metastatic non-small cell lung (NSCLC) cancer patients. METHODS: In a single
      institution retrospective review 173 patients with metastatic NSCLC diagnosed
      between Jan 1 2000 and June 30 2011 were included. ALI was calculated as (BMI x
      Alb / NLR) where BMI = body mass index, Alb = serum albumin, NLR (neutrophil
      lymphocyte ratio, a marker of systemic inflammation). Patients were divided into
      low inflammation (ALI >= 18) and high inflammation (ALI < 18) groups. Kaplan
      Meier method was used to estimate progression free survival and overall survival.
      Log-rank test were used to compare the survivals among various factors.
      Multivariate Cox regression was used to perform survival analysis in order to
      estimate the hazards ratio for various factors. RESULTS: Among 173 patients
      median age was 57 years, 67% were male, 52% had adenocarcinoma. Patients with an
      ALI score of < 18 suggesting high systemic inflammation were significantly more
      likely to have more than 2 sites of metastatic disease, have poor performance
      status and less likely to receive any chemotherapy. Their median progression free
      survival and overall survival was 2.4 months and 3.4 months as opposed to 5.1
      months and 8.3 months in patients with ALI >18 (P < 0.001). On multi-variate
      analysis ALI score of <18 (1.42, 95% CI 1.003-2.01) remained significantly
      associated with worse outcome. CONCLUSION: ALI (<18) at diagnosis is an
      independent marker of poor outcome in patients with advanced NSCLC.

PMID- 23530867
TI  - Carrier multiplication in semiconductor nanocrystals: influence of size, shape,
      and composition.
AB  - During carrier multiplication (CM), also known as multiexciton generation (MEG),
      absorption of a single photon produces multiple electron-hole pairs, or excitons.
      This process can appreciably increase the efficiency of photoconversion, which is
      especially beneficial in photocatalysis and photovoltaics. This Account reviews
      recent progress in understanding the CM process in semiconductor nanocrystals
      (NCs), motivated by the challenge researchers face to quickly identify candidate
      nanomaterials with enhanced CM. We present a possible solution to this problem by
      showing that, using measured biexciton Auger lifetimes and intraband relaxation
      rates as surrogates for, respectively, CM time constants and non-CM energy-loss
      rates, we can predict relative changes in CM yields as a function of composition.
      Indeed, by studying PbS, PbSe, and PbTe NCs of a variety of sizes we determine
      that the significant difference in CM yields for these compounds comes from the
      dissimilarities in their non-CM relaxation channels, i.e., the processes that
      compete with CM. This finding is likely general, as previous observations of a
      material-independent, "universal" volume-scaling of Auger lifetimes suggest that
      the timescale of the CM process itself is only weakly affected by NC composition.
      We further explore the role of nanostructure shape in the CM process. We observe
      that a moderate elongation (aspect ratio of 6-7) of PbSe NCs can cause up to an
      approximately two-fold increase in the multiexciton yield compared to spherical
      nanoparticles. The increased Auger lifetimes and improved charge transport
      properties generally associated with elongated nanostructures suggest that lead
      chalcogenide nanorods are a promising system for testing CM concepts in practical
      photovoltaics. Historically, experimental considerations have been an important
      factor influencing CM studies. To this end, we discuss the role of NC
      photocharging in CM measurements. Photocharging can distort multiexciton
      dynamics, leading to erroneous estimations of the CM yield. Here, we show that in
      addition to distorting time-resolved CM signals, photocharging also creates
      spectral signatures that mimic CM. This re-emphasizes the importance of a careful
      analysis of the potential effect of charged species in both optical and
      photocurrent-based measurements of this process. 

PMID- 23530868
TI  - Cutaneous alternariosis with trichosporon infection in a heart transplant
      recipient: a case report.
AB  - Cutaneous alternariosis infection occurs mainly in immunocompromised individuals.
      The incidence of alternariosis in a heart transplant recipient is infrequent.
      Coincidence of the aforementioned infection with additional fugal agents is rare.
      We describe a case of alternariosis with Trichosporon fungal infection in a
      patient who was successfully treated with combined antifungal therapy, modulation
      of immunosuppressive regimen, and blood glucose management. The patient had a
      good response to treatment, and has had an uneventful 1-year follow-up at the
      time of this writing. 

PMID- 23530869
TI  - An unusual cause of ankle pain: fracture of a talocalcaneal coalition as a
      differential diagnosis in an acute ankle sprain: a case report and literature
      review.
AB  - BACKGROUND: The acute ankle sprain is one of the most common injuries seen in
      trauma departments. Ankle sprains have an incidence of about one injury per 10
      000 people a day. In contrast tarsal coalition is a rare condition occurring in
      not more than one percent of the population. CASE PRESENTATION: We present the
      case of a 23 year old male patient with pain and local swelling after an acute
      ankle sprain. Initial clinical and radiological examination showed no
      pathologies. Due to prolonged pain, swelling and the inability of the patient to
      weight bear one week after trauma further diagnostics was performed. Imaging
      studies (MRI and CT) revealed a fracture of a talocalcaneal coalition. To the
      knowledge of the authors no fracture of a coalition was reported so far.
      CONCLUSION: This report highlights the presentation of symptomatic coalitions
      following trauma and furthermore, it points out the difficulties in the diagnosis
      and treatment of a rare entity after a common injury. A diagnostic algorithm has
      been developed to ensure not to miss a severe injury.

PMID- 23530870
TI  - Projected cost-effectiveness of repeat high-risk human papillomavirus testing
      using self-collected vaginal samples in the Swedish cervical cancer screening
      program.
AB  - BACKGROUND: Human papillomavirus (HPV) testing is not currently used in primary
      cervical cancer screening in Sweden, and corresponding cost-effectiveness is
      unclear. OBJECTIVE: From a societal perspective, to evaluate the cost
      effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples.
      DESIGN: A cost-effectiveness analysis. SETTING: The Swedish organized cervical
      cancer screening program. METHODS: We constructed a model to simulate the natural
      history of cervical cancer using Swedish data on cervical cancer risk. For the
      base-case analysis we evaluated two screening strategies with different screening
      intervals: (i) cytology screening throughout the woman's lifetime (i.e.
      "conventional cytology strategy") and (ii) conventional cytology screening until
      age 35 years, followed by HR-HPV testing using self-collected vaginal samples in
      women aged >=35 years (i.e. "combination strategy"). Sensitivity analyses were
      performed, varying model parameters over a significant range of values to
      identify cost-effective screening strategies. MAIN OUTCOME MEASURES: Average
      lifetime cost, discounted and undiscounted life-years gained, reduction in
      cervical cancer risk, incremental cost-effectiveness ratios with and without the
      cost of added life-years. RESULTS: Depending on screening interval, the
      incremental cost-effectiveness ratios for the combination strategy ranged from
      ?43,000 to ?180,000 per life-years gained without the cost of added life-years,
      and from ?74,000 to ?206,000 with costs of added life-years included. CONCLUSION:
      The combination strategy with a 5-year screening interval is potentially cost
      effective compared with no screening, and with current screening practice when
      using a threshold value of ?80,000 per life-years gained.

PMID- 23530871
TI  - RNAseq versus genome-predicted transcriptomes: a large population of novel
      transcripts identified in an Illumina-454 Hydra transcriptome.
AB  - BACKGROUND: Evolutionary studies benefit from deep sequencing technologies that
      generate genomic and transcriptomic sequences from a variety of organisms. Genome
      sequencing and RNAseq have complementary strengths. In this study, we present the
      assembly of the most complete Hydra transcriptome to date along with a
      comparative analysis of the specific features of RNAseq and genome-predicted
      transcriptomes currently available in the freshwater hydrozoan Hydra vulgaris.
      RESULTS: To produce an accurate and extensive Hydra transcriptome, we combined
      Illumina and 454 Titanium reads, giving the primacy to Illumina over 454 reads to
      correct homopolymer errors. This strategy yielded an RNAseq transcriptome that
      contains 48'909 unique sequences including splice variants, representing
      approximately 24'450 distinct genes. Comparative analysis to the available genome
      predicted transcriptomes identified 10'597 novel Hydra transcripts that encode
      529 evolutionarily-conserved proteins. The annotation of 170 human orthologs
      points to critical functions in protein biosynthesis, FGF and TOR signaling,
      vesicle transport, immunity, cell cycle regulation, cell death, mitochondrial
      metabolism, transcription and chromatin regulation. However, a majority of these
      novel transcripts encodes short ORFs, at least 767 of them corresponding to
      pseudogenes. This RNAseq transcriptome also lacks 11'270 predicted transcripts
      that correspond either to silent genes or to genes expressed below the detection
      level of this study. CONCLUSIONS: We established a simple and powerful strategy
      to combine Illumina and 454 reads and we produced, with genome assistance, an
      extensive and accurate Hydra transcriptome. The comparative analysis of the
      RNAseq transcriptome with genome-predicted transcriptomes lead to the
      identification of large populations of novel as well as missing transcripts that
      might reflect Hydra-specific evolutionary events.

PMID- 23530872
TI  - Similar range of motion and function after resurfacing large-head or standard
      total hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: Large-size hip articulations may improve range of motion
      (ROM) and function compared to a 28-mm THA, and the low risk of dislocation
      allows the patients more activity postoperatively. On the other hand, the greater
      extent of surgery for resurfacing hip arthroplasty (RHA) could impair
      rehabilitation. We investigated the effect of head size and surgical procedure on
      postoperative rehabilitation in a randomized clinical trial (RCT). Methods We
      followed randomized groups of RHAs, large-head THAs and standard THAs at 2
      months, 6 months, 1 and 2 years postoperatively, recording clinical
      rehabilitation parameters. RESULTS: Large articulations increased the mean total
      range of motion by 13 degrees  during the first 6 postoperative months. The
      increase was not statistically significant and was transient. The 2-year total
      ROM (SD) for RHA, standard THA, and large-head THA was 221 degrees  (35), 232
      degrees  (36), and 225 degrees  (30) respectively, but the differences were not
      statistically significant. The 3 groups were similar regarding Harris hip score,
      UCLA activity score, step rate, and sick leave. INTERPRETATION: Head size had no
      influence on range of motion. The lack of restriction allowed for large
      articulations did not improve the clinical and patient-perceived outcomes. The
      more extensive surgical procedure of RHA did not impair the rehabilitation. This
      project is registered at ClinicalTrials.gov under # NCT01113762.

PMID- 23530873
TI  - Predictors of periprosthetic fracture after total knee replacement: an analysis
      of 21,723 cases.
AB  - BACKGROUND AND PURPOSE: Periprosthetic fracture is a devastating complication of
      total knee replacement (TKR). Most published studies have not comprehensively
      assessed clinical and demographic predictors. We wanted to determine the
      incidence and predictors of postoperative periprosthetic fracture after primary
      and revision TKR. PATIENTS AND METHODS: We used prospectively collected data in
      the Mayo Clinic Total Joint Registry on all patients who underwent primary or
      revision TKR at the Mayo Clinic, Rochester, from 1989 through 2008. We assessed
      incidence of postoperative periprosthetic fractures and modifiable (comorbidity,
      body mass index) and unmodifiable factors (age, sex, operative diagnosis, ASA
      class, previous cardiac disease, and previous thromboembolic disease) as
      predictors of postoperative periprosthetic fractures. We used multivariable
      adjusted Cox regression analyses separately for primary and revision TKR.
      RESULTS: 12,914 patients underwent 17,633 primary TKRs and 3,286 patients
      underwent 4,090 revision TKRs during the period 1989-2008. 1.1% of patients
      (188/17,633) after primary TKR and 2.5% of patients (104/4,090) after revision
      TKR sustained a postoperative periprosthetic fracture on or after postoperative
      day 1. Older age was associated with lower risk of periprosthetic fractures after
      primary TKR (p < 0.001). Compared to <= 60 years, risk was lower for ages 61-70
      years (hazard ratio (HR) = 0.5, 95% confidence interval (CI): 0.3-0.7)) and 71-80
      years (HR = 0.6, CI: 0.4-0.8), but not for age > 80 years (HR = 0.9, CI: 0.5
      1.6). In revision TKR cohort, a diagnosis of non-union (HR = 4.9, CI: 1.2-20),
      infection (HR = 2.9, CI: 1.3-6.4) or previous surgery with components removed (HR
      = 2.1, CI: 1.3-3.4) increased the risk of postoperative periprosthetic fracture,
      compared to a diagnosis of loosening/wear/osteolysis. INTERPRETATION: We
      identified significant risk factors for periprosthetic fracture after primary and
      revision TKR. Patients with these risk factors can be informed by their surgeons
      of increased risk of this uncommon, but serious complication of TKR.

PMID- 23530874
TI  - Patient and implant survival following joint replacement because of metastatic
      bone disease.
AB  - BACKGROUND: Patients suffering from a pathological fracture or painful bony
      lesion because of metastatic bone disease often benefit from a total joint
      replacement. However, these are large operations in patients who are often weak.
      We examined the patient survival and complication rates after total joint
      replacement as the treatment for bone metastasis or hematological diseases of the
      extremities. PATIENTS AND METHODS: 130 patients (mean age 64 (30-85) years, 76
      females) received 140 joint replacements due to skeletal metastases (n = 114) or
      hematological disease (n = 16) during the period 2003-2008. 21 replaced joints
      were located in the upper extremities and 119 in the lower extremities. Clinical
      and survival data were extracted from patient files and various registers.
      RESULTS: The probability of patient survival was 51% (95% CI: 42-59) after 6
      months, 39% (CI: 31-48) after 12 months, and 29% (CI: 21-37) after 24 months. The
      following surgical complications were seen (8 of which led to additional
      surgery): 2-5 hip dislocations (n = 8), deep infection (n = 3), peroneal palsy (n
      = 2), a shoulder prosthesis penetrating the skin (n = 1), and disassembly of an
      elbow prosthesis (n = 1). The probability of avoiding all kinds of surgery
      related to the implanted prosthesis was 94% (CI: 89-99) after 1 year and 92% (CI:
      85-98) after 2 years. CONCLUSION: Joint replacement operations because of
      metastatic bone disease do not appear to have given a poorer rate of patient
      survival than other types of surgical treatment, and the reoperation rate was
      low.

PMID- 23530875
TI  - Pediatric glioblastoma with oligodendroglioma component: aggressive clinical
      phenotype with distinct molecular characteristics.
AB  - The 2007 World Health Organization classification defined a new variant of
      glioblastoma (GBM) containing oligodendroglioma foci as GBM with an
      oligodendroglioma component (GBMO), which shows a favorable clinical outcome
      compared with "classic" GBM. However, all of the reported cases of GBMO have been
      adult cases, with no previous reports of pediatric cases. In this report, we
      demonstrated molecular characteristics of a pediatric GBMO case, showing
      aggressive clinical behavior with 8-month overall survival. The case showed
      neither isocitrate dehydrogenase 1/2 genes (IDH1/2) mutation nor 1p/19q co
      deletion, a hallmark of oligodendroglioal tumors. In addition, microsatellite
      instability, leading to the putative mechanism of temozolomide (TMZ) resistance,
      was frequently detected. Molecular genetic analysis may provide critical
      prognostic and therapeutic insights, especially for the pediatric glioma
      containing oligodendroglioma components. 

PMID- 23530876
TI  - Validation of the chronic disease score-infectious disease (CDS-ID) for the
      prediction of hospital-associated clostridium difficile infection (CDI) within a
      retrospective cohort.
AB  - BACKGROUND: Aggregate comorbidity scores are useful for summarizing risk and
      confounder control in studies of hospital-associated infections. The Chronic
      Disease Score - Infectious Diseases (CDS-ID) was developed for this purpose, but
      it has not been validated for use in studies of Clostridium difficile Infection
      (CDI). The aim of this study was to assess the discrimination, calibration and
      potential for confounder control of CDS-ID compared to age alone or individual
      comorbid conditions. METHODS: Secondary analysis of a retrospective cohort study
      of adult inpatients with 2 or more days of antibiotic exposure at a tertiary care
      facility during 2005. Logistic regression models were used to predict the
      development of CDI up to 60 days post-discharge. Model discrimination and
      calibration were assessed using the c-statistic and Hosmer-Lemeshow (HL) tests,
      respectively. C-statistics were compared using chi-square tests. RESULTS: CDI
      developed in 185 out of 7,792 patients. The CDS-ID was a better standalone
      predictor of CDI than age (c-statistic 0.653 vs 0.609, P=0.04). The best
      discrimination was observed when CDS-ID and age were both used to predict CDI (c
      statistic 0.680). All models had acceptable calibration (P>0.05). CONCLUSION: The
      CDS-ID is a valid tool for summarizing risk of CDI associated with comorbid
      conditions.

PMID- 23530877
TI  - Type 1 diabetes mellitus abrogates compensatory augmentation of myocardial
      neuregulin-1beta/ErbB in response to myocardial infarction resulting in worsening
      heart failure.
AB  - BACKGROUND: Diabetes mellitus (DM) patients surviving myocardial infarction (MI)
      exhibit a substantially higher incidence of subsequent heart failure (HF).
      Neuregulin (NRG)-1 and erythroblastic leukemia viral oncogene homolog (ErbB)
      receptors have been shown to play a critical role in maintenance of cardiac
      function. However, whether myocardial NRG-1/ErbB is altered during post-MI HF
      associated with DM remains unknown. The aim of this study was to determine the
      impact of type 1 DM on the myocardial NRG-1/ErbB system following MI in relation
      to residual left ventricular (LV) function. METHODS: Type 1 DM was induced in
      rats via administration of streptozotocin (65 mg/kg, i.p.). Control rats were
      injected with citrate buffer (vehicle) only. Two weeks after induction of type 1
      DM, MI was produced in DM and non-DM rats by ligation of the left coronary
      artery. Sham MI rats underwent the same surgical procedure with the exception
      that the left coronary artery was not ligated. At 4 weeks after surgery, residual
      in vivo LV function was assessed via echocardiography. Myocardial protein
      expression of NRG-1beta, ErbB2 and ErbB4 receptors, and MDM2 (a downstream
      signaling pathway induced by NRG-1 that has been implicated in cell survival) was
      assessed in the remaining, viable LV myocardium by Western blotting. Changes in
      ErbB receptor localization in the surviving LV myocardium of diabetic and non
      diabetic post-MI rats was determined using immunohistochemistry techniques.
      RESULTS: At 4 weeks post-MI, echocardiography revealed that LV fractional
      shortening (FS) and LV ejection fraction (EF) were significantly lower in the DM
      + MI group compared to the MI group (LVFS: 17.9 +/- 0.7 vs. 25.2 +/- 2.2; LVEF:
      35.5 +/- 1.4 vs. 47.5 +/- 3.5, respectively; P < 0.05), indicating an increased
      functional severity of HF among the DM + MI rats. Up-regulation of NRG-1beta and
      ErbB2 protein expression in the MI group was abrogated in the DM + MI group
      concurrent with degradation of MDM2, a downstream negative regulator of p53.
      ErbB2 and ErbB4 receptors re-localized to cardiac myocyte nuclei in failing type
      1 diabetic post-MI hearts. CONCLUSIONS: Type 1 DM prevents compensatory up
      regulation of myocardial NRG-1/ErbB after MI coincident with an increased
      severity of HF.

PMID- 23530878
TI  - Phase I study of a modified regimen of 90Yttrium-ibritumomab tiuxetan for
      relapsed or refractory follicular or transformed CD20+ non-Hodgkin lymphoma.
AB  - Radioimmunotherapy capitalizes on the radiosensitivity of non-Hodgkin lymphoma
      (NHL) and the targeted nature of monoclonal antibodies. In an attempt to reverse
      bone marrow infiltration with B-cells and optimize the biodistribution of Yttrium
      90 (90Y)-ibritumomab tiuxetan, we conducted a phase I study combining a single
      course of 90Y-ibritumomab tiuxetan after a 4-weekly course of rituximab in
      relapsed or refractory low-grade or transformed CD20+ B-cell NHLs with <25%
      marrow involvement. The 0.4 mCi/kg dose was associated with 80% grade-4
      cytopenias. Dose escalation was held, and 6 patients were enrolled at a 0.3
      mCi/kg cohort. As the 0.3 mCi/kg dose was well tolerated, the 0.4 mCi/kg cohort
      was expanded to 6 additional patients. In the expansion cohort, grade-4 cytopenia
      developed in 33%. Further dose escalation was held, and the maximum tolerated
      dose was determined at 0.4 mCi/kg. With this regimen, marrow involvement
      decreased in all patients with complete clearance in 50%. The overall response
      rate was 82%. With a median follow-up of 31.7 months, the median progression-free
      survival and time to next treatment were 12.3 and 10.9 months, respectively.
      Although this regimen was associated with a high response rate, the hematologic
      toxicity was higher than with the standard 90Y-ibritumomab tiuxetan regimen.

PMID- 23530879
TI  - HSP27 as a potential preneoplastic marker in patients with chronic kidney
      disease.

PMID- 23530880
TI  - Meta-analysis: colonoscopic post-polypectomy bleeding in patients on continued
      clopidogrel therapy.
AB  - BACKGROUND: Current guidelines recommend the cessation of clopidogrel therapy 5
      days and 7-10 days prior to colonoscopic polypectomy. Recent studies have
      advocated for continued clopidogrel as post-polypectomy bleeding (PPB) rates have
      been similar to those in the general population not on antithrombotic therapy.
      AIM: To assess colonoscopic post-polypectomy bleeding in patients on continued
      clopidogrel therapy. METHODS: A literature search was conducted for studies that
      investigated PPB in patients on continued clopidogrel therapy. The primary
      outcome of interest was the pooled relative risk ratio (RR) of colonoscopic PPB
      in patients on continued clopidogrel therapy vs. controls. Secondary outcomes
      were a comparison of immediate and delayed colonoscopy PPB in patients on
      continued clopidogrel therapy vs. controls. RESULTS: Five observational studies
      included 574 subjects on continued clopidogrel therapy and 6169 control subjects.
      The pooled RR for PPB on continued clopidogrel therapy was 2.54 (95% CI 1.68
      3.84, P < 0.00001). For immediate PPB there was a nonsignificant pooled RR of
      1.76 (95% CI 0.90-3.46, P = 0.10), and delayed PPB there was a significant pooled
      RR of 4.66 (95% CI 2.37-9.17, P < 0.00001). CONCLUSIONS: The results of this meta
      analysis suggest that continued clopidogrel increases the risk of delayed but not
      immediate post-polypectomy bleeding. Clopidogrel interruption in individuals with
      coronary artery disease predisposes to serious acute ischaemic events. In high
      risk patients, endoscopists should be cognisant of these risks and consider
      deferring elective colonoscopy and polypectomy until it is considered safe to
      interrupt clopidogrel therapy.

PMID- 23530881
TI  - Bayesian decision-network modeling of multiple stakeholders for reef ecosystem
      restoration in the coral triangle.
AB  - Proposals for marine conservation measures have proliferated in the last 2
      decades due to increased reports of fishery declines and interest in
      conservation. Fishers and fisheries managers have often disagreed strongly when
      discussing controls on fisheries. In such situations, ecosystem-based models and
      fisheries-stock assessment models can help resolve disagreements by highlighting
      the trade-offs that would be made under alternative management scenarios. We
      extended the analytical framework for modeling such trade-offs by including
      additional stakeholders whose livelihoods and the value they place on
      conservation depend on the condition of the marine ecosystem. To do so, we used
      Bayesian decision-network models (BDNs) in a case study of an Indonesian coral
      reef fishery. Our model included interests of the fishers and fishery managers;
      individuals in the tourism industry; conservation interests of the state,
      nongovernmental organizations, and the local public; and uncertainties in
      ecosystem status, projections of fisheries revenues, tourism growth, and levels
      of interest in conservation. We calculated the total utility (i.e., value) of a
      range of restoration scenarios. Restricting net fisheries and live-fish fisheries
      appeared to be the best compromise solutions under several combinations of
      settings of modeled variables. Results of our case study highlight the
      implications of alternate formulations for coral reef stakeholder utility
      functions and discount rates for the calculation of the net benefits of
      alternative fisheries management options. This case study may also serve as a
      useful example for other decision analyses with multiple stakeholders.

PMID- 23530882
TI  - Scleroderma: skin stiffness assessment using the stress-strain relationship under
      progressive suction.
AB  - INTRODUCTION: A few non-invasive biometrological methods are available for
      monitoring skin stiffening in systemic scleroderma. Among them, the Cutometer(r)
      is used for years by several clinical teams. OBJECTIVES: To revisit the
      microscopic structure of the dermal fibrous networks in scleroderma and the
      relationship with changes in viscoelasticity. METHODS: The suction method
      delivered by the Cutometer(r) was applied following the progressive stress-vs
      strain modality. RESULTS: The test procedure was sensitive enough to document the
      initial progression steps of acroscleroderma. Four stages were thus identified
      including i) the incipient, ii) the progressive, iii) the overt, and iv) the
      regressive acroscleroderma. CONCLUSION: The non-invasive determination of skin
      biomechanical functions is relevant both in routine clinical practice and in
      antisclerotic drug development. It is complementary although not a substitute for
      the determination of selected serum biomarkers.

PMID- 23530883
TI  - Analytical performance validation of a coronary heart disease risk assessment
      multi-analyte proteomic test.
AB  - BACKGROUND: Coronary heart disease (CHD) remains prevalent despite efforts to
      improve CHD risk assessment. The authors developed a multi-analyte immunoassay
      based CHD risk assessment (CHDRA) algorithm, clinically validated in a
      multicenter study, to improve CHDRA in intermediate risk individuals. OBJECTIVE:
      Clinical laboratory validation of the CHDRA biomarker assays' analytical
      performance. METHODS: Multiplexed immunoassay panels developed for the seven
      CHDRA assays were evaluated with donor sera in a clinical laboratory.
      Specificity, sensitivity, interfering substances and reproducibility of the CHDRA
      assays, along with the effects of pre-analytical specimen processing, were
      evaluated. RESULTS: Analytical measurements of the CHDRA panel proteins (CTACK,
      Eotaxin, Fas Ligand, HGF, IL-16, MCP-3 and sFas) exhibited acceptable accuracy
      (80 - 120%), cross-reactivity (< 1%), interference (< 30% at high concentrations
      of bilirubin, lipids, hemoglobin and HAMA), sensitivity and reproducibility (<
      20% CV across multiple runs, operators and instruments). Recoveries from donor
      sera subjected to typical clinical laboratory pre-analytical conditions were
      within 80 - 120%. The pre-analytical variables did not substantively impact the
      CHDRA scores. CONCLUSIONS: The CHDRA panel analytical validation in a clinical
      laboratory meets or exceeds the specifications established during the clinical
      utility studies. Risk score reproducibility across multiple test scenarios
      suggests the assays are not susceptible to clinical laboratory pre-analytical and
      analytical variation.

PMID- 23530884
TI  - Novel biomarkers for the prediction of metastasis in colorectal cancer.
AB  - INTRODUCTION: In patients with metastatic colorectal cancers, multimodal
      management and the use of biological agents such as monoclonal antibodies have
      had major positive effects on survival. The ability to predict which patients may
      be at 'high risk' of distant metastasis could have major implications on patient
      management. Histomorphological, immunohistochemical or molecular biomarkers are
      currently being investigated in order to test their potential value as predictors
      of metastasis. AREAS COVERED: Here, the author reviews the clinical and
      functional data supporting the investigation of three novel promising biomarkers
      for the prediction of metastasis in patients with colorectal cancer: tumor
      budding, Raf1 kinase inhibitor protein (RKIP) and metastasis-associated in colon
      cancer-1 (MACC1). EXPERT OPINION: The lifespan of most potential biomarkers is
      short as evidenced by the rare cases that have successfully made their way into
      daily practice such as KRAS or microsatellite instability (MSI) status. Although
      the three biomarkers reviewed herein have the potential to become important
      predictive biomarkers of metastasis, they have similar hurdles to overcome before
      they can be implemented into clinical management: standardization and validation
      in prospective patient cohorts.

PMID- 23530885
TI  - Novel biomarkers for bipolar disorder.
AB  - INTRODUCTION: Bipolar disorder is diagnosed on the basis of patient and/or family
      reports and behavioral observation. Traditionally regarded as an affective
      disorder involving behavioral changes, bipolar disorder has been reconceptualized
      as a multisystem disease associated with mood, cognitive, metabolic, autonomic
      and sleep/wake dysfunctions. Accordingly, recent studies have focused on the
      identification of biomarkers related to the pathophysiological mechanisms
      underlying the development, clinical presentation and course of bipolar disorder.
      AREAS COVERED: This article provides an overview of the available literature
      regarding circulating peripheral and neuroimaging biomarkers in bipolar disorder.
      Neurotrophic factors, immune parameters, oxidative stress parameters, hormones
      and neuroimaging findings were taken into consideration. EXPERT OPINION:
      Biomarkers research in bipolar disorder is a new field with an expanding
      knowledge. Current evidence suggests that a single biomarker will not be able to
      cover the biological and clinical complexity of bipolar disorder. Alternatively,
      a composite of biomarkers, including neurotrophic factors, cytokines and
      oxidative stress molecules, may be promising to identify altered mood states and
      neuroprogression in bipolar disorder.

PMID- 23530886
TI  - Molecular diagnosis of hemochromatosis.
AB  - INTRODUCTION: The discovery of hemochromatosis genes and the availability of
      molecular-genetic tests considerably modified the knowledge of the disease
      relative to physiopathology, penetrance, and expression, and had major impact in
      the diagnostic settings. AREAS COVERED: Hemochromatosis is a heterogenous
      disorder at both genetic and phenotypic level. The review discusses criteria to
      define patients' iron phenotype and to use molecular tests to diagnose HFE
      related and non-HFE hemochromatosis. The material examined includes articles
      published in the journals covered by PubMed US National Library of Medicine. The
      author has been working in the field of iron overload diseases for several years
      and has contributed 18 of the papers cited in the references. EXPERT OPINION:
      Hemochromatosis genotyping is inseparable from phenotype characterization. A full
      clinical assessment is needed and DNA test performed when data suggest a clear
      indication of suspicion of being at risk for HH. HFE testing for p.Cys282Tyr
      mutation and p.His63Asp variant is the first molecular diagnostic step.
      Genotyping for rare mutations can be offered to patients with negative first
      level HFE testing who have iron overload with no other explanation and should be
      performed in referral centers for iron overload disorders that can provide
      genetic advice and in-house genotyping services.

PMID- 23530887
TI  - Accuracy and limitations of diagnostic methods for avascular necrosis of the hip.
AB  - INTRODUCTION: Femoral head avascular necrosis (FHAVN) is the result of
      irreversible anoxia of the subchondral bone. The death of bone cells can cause
      articular collapse and pain, and in turn usually leads to degenerative arthritis.
      FHAVN is a common disorder, affecting mainly young male adults. Reliability,
      accuracy and prognostic value of any classification system are important in
      evaluation and treatment of FHAVN. AREAS COVERED: Although in the past,
      scintigraphy and CT and more recently PET have been used for diagnosing AVN,
      currently the most important imaging methods included in the most widely used
      classification systems, consist of radiographs and magnetic resonance imaging
      (MRI). The latter is used in major classification systems for early detection
      (pre-radiographic stage) of FHAVN and for assessing lesion size and location
      before collapse of the articular surface occurs. The purpose of this review is to
      present the current data regarding the accuracy of the X-rays and MRI in
      diagnosing, monitoring and postoperative evaluation of FHAVN. EXPERT OPINION: The
      author's opinion is that MRI may contribute to improve staging, investigate
      radiologically occult collapse, depict other causes of disability and pain,
      assess prognosis and evaluate treatment. Newer MRI techniques, such as diffusion
      weighted imaging and perfusion imaging, have not yet provided additional and
      clinically useful information.

PMID- 23530888
TI  - Efficacy of methods used for the diagnosis of bacterial vaginosis.
AB  - INTRODUCTION: Bacterial vaginosis (BV) has been associated with pelvic
      inflammatory disease, adverse pregnancy outcomes, increased susceptibility to
      sexually transmitted infections and infertility. Diagnosis of BV should be rapid,
      reliable and safe. This is especially vital in pregnant women where intervention
      may be necessary for the well-being of both the mother and the foetus. AREAS
      COVERED: This paper consulted PUBMED, LISTA and Web of Science for point-of-care
      and laboratory-based tests commonly used for the diagnosis and management of BV
      in pregnant women. An overview of strengths and weaknesses of the methods used
      may partially explain why treatment plans have failed. Differences in sampling
      and detection methods, time of gestation, inter-examiner variability and
      interpretation of data, and the use of different reference tests, amongst many
      other factors, complicated a meta-analysis of the data. EXPERT OPINION:
      Inconsistencies found in clinical and laboratory detection methods used for the
      monitoring of treatment have a direct impact on success rates. With current
      advances in technology, the diagnosis of BV is taking on a new perspective. New
      information implicating specific vaginal biofilms in adverse pregnancy outcomes
      through the application of advanced technology promises to change the way we view
      the aetiology, diagnosis and management of BV.

PMID- 23530889
TI  - Critical assessment of diabetic xerosis.
AB  - INTRODUCTION: Diabetes mellitus is commonly responsible for skin changes
      including discrete to mild xerosis. AREAS COVERED: This review focuses on some
      selected relevant bioinstrumental methods assessing diabetes xerosis. Peer
      reviewed articles on objective non-invasive methods were scrutinized. The
      reviewed methods address i) the xerosis severity grading scale, ii)
      corneodynamics referring to the desquamation rate, iii) electrometric assessment
      of skin hydration including skin capacitance mapping and iv) implication of the
      imperceptible perspiration. The subjective clinical assessment often fails to
      disclose diabetic xerosis with confidence and precision. By contrast, a
      multipronged biometrological approach identifies a cluster of diabetic patients
      who experience alterations in the structural and functional maturation of the
      stratum corneum. EXPERT OPINION: A multipronged biometrological approach helps
      identifying the changes in the stratum corneum of diabetic xerosis. There is a
      continuum between the 'dry skin' feeling, xerosis and ichthyosiform
      presentations, particularly on the shins and feet of diabetic patients.

PMID- 23530890
TI  - Neutrophil gelatinase-associated lipocalin as diagnostic and prognostic tool for
      cardiovascular disease and heart failure.
AB  - INTRODUCTION: Cardiovascular disease (CVD) has been a burden on the healthcare
      system for decades and has increased the need for earlier diagnosis, better risk
      stratification and cost- effective treatment to reduce the rates of
      hospitalization. Biomarker research has broadened our knowledge base, shedding
      more light on the underlying pathophysiological mechanisms associated with the
      development of heart disorders. Recent technological advances have made it
      possible to use noninvasive and cost-effective biomarkers for identifying
      patients who are at risk of developing coronary heart disease and
      atherosclerosis. AREAS COVERED: In this paper the authors review the development
      of neutrophil gelatinase-associated lipocalin (NGAL) as a cardiac biomarker,
      highlighting studies that validate its use in predicting acute changes in
      patients with an array of cardiac disorders, and stake a case for the use of NGAL
      as a clinical diagnostic tool to predict outcomes in patients with CVD. EXPERT
      OPINION: The authors believe that NGAL should be used as a clinical diagnostic
      tool to predict outcomes in patients with CVD. Growing evidence has illustrated
      the biological role that neutrophils, such as NGAL, play in inflammation and
      atherosclerosis. Further studies are needed to determine NGAL's stability in
      serum and urine, and to substantiate its widespread use, but there are expanding
      possibilities for this biomarker in clinical practice.

PMID- 23530892
TI  - Patterns and implications of extensive heterochrony in carnivoran cranial suture
      closure.
AB  - Heterochronic changes in the rate or timing of development underpin many
      evolutionary transformations. In particular, the onset and rate of bone
      development have been the focus of many studies across large clades. In contrast,
      the termination of bone growth, as estimated by suture closure, has been studied
      far less frequently, although a few recent studies have shown this to represent a
      variable, although poorly understood, aspect of developmental evolution. Here, we
      examine suture closure patterns across 25 species of carnivoran mammals, ranging
      from social-insectivores to hypercarnivores, to assess variation in suture
      closure across taxa, identify heterochronic shifts in a phylogenetic framework
      and elucidate the relationship between suture closure timing and ecology. Our
      results show that heterochronic shifts in suture closure are widespread across
      Carnivora, with several shifts identified for most major clades. Carnivorans
      differ from patterns identified for other mammalian clades in showing high
      variability of palatal suture closure, no correlation between size and level of
      suture closure, and little phylogenetic signal outside of musteloids. Results
      further suggest a strong influence of feeding ecology on suture closure pattern.
      Most of the species with high numbers of heterochronic shifts, such as the walrus
      and the aardwolf, feed on invertebrates, and these taxa also showed high
      frequency of closure of the mandibular symphysis, a state that is relatively rare
      among mammals. Overall, caniforms displayed more heterochronic shifts than
      feliforms, suggesting that evolutionary changes in suture closure may reflect the
      lower diversity of cranial morphology in feliforms.

PMID- 23530893
TI  - Detection of multiple species of human Paragonimus from Mexico using
      morphological data and molecular barcodes.
AB  - Paragonimus mexicanus is the causal agent of human paragonimiasis in several
      countries of the Americas. It is considered to be the only species of the genus
      present in Mexico, where it is responsible for human infection. Through the
      investigation of P. mexicanus specimens from several places throughout Mexico, we
      provide morphological, molecular and geographical evidence that strongly suggests
      the presence of at least three species from this genus in Mexico. These results
      raise questions regarding the diagnosis, treatment, prophylaxis and control of
      human paragonimiasis in Mexico. We also provide a brief discussion regarding
      biodiversity inventories and the convenience of providing molecular and
      morphological information in biodiversity studies. 

PMID- 23530894
TI  - Insulin-like growth factor-I enhances proliferation and differentiation of human
      mesenchymal stromal cells in vitro.
AB  - Human mesenchymal stromal cells (hMSCs) offer great potential for bone tissue
      engineering applications, but their in vivo performance remains limited.
      Preconditioning of these cells with small molecules to improve their
      differentiation before implantation, or incorporation of growth factors are
      possible solutions. Insulin-like growth factor-1 (IGF-1) is one of the most
      abundant growth factors in bone, involved in growth, development, and metabolism,
      but its effects on hMSCs are still subject of debate. Here we examined the
      effects of IGF-1 on proliferation and differentiation of hMSCs in vitro and we
      found that serum abolished the effects of IGF-1. Only in the absence of serum,
      IGF-1 increased proliferation, alkaline phosphatase expression, and osteogenic
      gene expression of hMSCs. Furthermore, we examined synergistic effects of bone
      morphogenetic protein-2 (BMP-2) and IGF-1 and, although IGF-1 enhanced BMP-2
      induced mineralization, IGF-1 only slightly affected in vivo bone formation. 

PMID- 23530895
TI  - Hybrid lipids increase the probability of fluctuating nanodomains in mixed
      membranes.
AB  - A ternary mixture model is proposed to describe composition fluctuations in mixed
      membranes composed of saturated, unsaturated, and hybrid lipids (with one
      saturated and one unsaturated hydrocarbon chain). The hybrids are line-active and
      can reduce the packing incompatibility between the saturated and unsaturated
      lipids. We introduce a lattice model that extends previous studies by taking into
      account the dependence of the interactions of the hybrid lipids on their
      orientations in a simple way. A methodology to recast the free energy of the
      lattice model in terms of a continuous, isotropic field theory is proposed and
      used to analyze composition fluctuations in the one-phase region (above the
      critical temperature). The effect of hybrid lipids on fluctuation domains rich in
      saturated/unsaturated lipids is predicted. The correlation length of such
      fluctuations decreases significantly with increasing amounts of hybrids; this
      implies that nanoscale fluctuation domains are more probable compared to the case
      with no hybrids. Smaller correlated fluctuation domains arise even when the
      temperature is close to a critical point, where very large correlation lengths
      are normally expected. This decrease in the correlation length is largest as the
      hybrid composition tends toward a crossover value above which stripelike
      fluctuations are predicted. This crossover value defines the Lifshitz line. The
      characteristic wavelength of the stripelike fluctuations is large close to the
      Lifshitz point but decreases toward a molecular size in a membrane that contains
      only hybrids. Micrometer size, stripelike domains have recently been observed
      experimentally in giant unilamelar vesicles (GUVs) made of saturated,
      unsaturated, and hybrid lipids. These results suggest that the line activity of
      hybrid lipids in such mixtures may be significant only at large hybrid fractions;
      in that regime, the interface between domains can be diffuse and several hybrid
      molecules with correlated orientations can separate saturated and unsaturated
      lipid regions.

PMID- 23530896
TI  - Affective and executive network processing associated with persuasive antidrug
      messages.
AB  - Previous research has highlighted brain regions associated with socioemotional
      processes in persuasive message encoding, whereas cognitive models of persuasion
      suggest that executive brain areas may also be important. The current study aimed
      to identify lateral prefrontal brain areas associated with persuasive message
      viewing and understand how activity in these executive regions might interact
      with activity in the amygdala and medial pFC. Seventy adolescents were scanned
      using fMRI while they watched 10 strongly convincing antidrug public service
      announcements (PSAs), 10 weakly convincing antidrug PSAs, and 10 advertisements
      (ads) unrelated to drugs. Antidrug PSAs compared with nondrug ads more strongly
      elicited arousal-related activity in the amygdala and medial pFC. Within antidrug
      PSAs, those that were prerated as strongly persuasive versus weakly persuasive
      showed significant differences in arousal-related activity in executive
      processing areas of the lateral pFC. In support of the notion that persuasiveness
      involves both affective and executive processes, functional connectivity analyses
      showed greater coactivation between the lateral pFC and amygdala during PSAs
      known to be strongly (vs. weakly) convincing. These findings demonstrate that
      persuasive messages elicit activation in brain regions responsible for both
      emotional arousal and executive control and represent a crucial step toward a
      better understanding of the neural processes responsible for persuasion and
      subsequent behavior change.

PMID- 23530897
TI  - Amygdala functional connectivity with medial prefrontal cortex at rest predicts
      the positivity effect in older adults' memory.
AB  - As people get older, they tend to remember more positive than negative
      information. This age-by-valence interaction has been called "positivity effect."
      The current study addressed the hypotheses that baseline functional connectivity
      at rest is predictive of older adults' brain activity when learning emotional
      information and their positivity effect in memory. Using fMRI, we examined the
      relationship among resting-state functional connectivity, subsequent brain
      activity when learning emotional faces, and individual differences in the
      positivity effect (the relative tendency to remember faces expressing positive
      vs. negative emotions). Consistent with our hypothesis, older adults with a
      stronger positivity effect had increased functional coupling between amygdala and
      medial PFC (MPFC) during rest. In contrast, younger adults did not show the
      association between resting connectivity and memory positivity. A similar age-by
      memory positivity interaction was also found when learning emotional faces. That
      is, memory positivity in older adults was associated with (a) enhanced MPFC
      activity when learning emotional faces and (b) increased negative functional
      coupling between amygdala and MPFC when learning negative faces. In contrast,
      memory positivity in younger adults was related to neither enhanced MPFC activity
      to emotional faces, nor MPFC-amygdala connectivity to negative faces.
      Furthermore, stronger MPFC-amygdala connectivity during rest was predictive of
      subsequent greater MPFC activity when learning emotional faces. Thus, emotion
      memory interaction in older adults depends not only on the task-related brain
      activity but also on the baseline functional connectivity. 

PMID- 23530898
TI  - A retinotopic attentional trace after saccadic eye movements: evidence from event
      related potentials.
AB  - Saccadic eye movements are a major source of disruption to visual stability, yet
      we experience little of this disruption. We can keep track of the same object
      across multiple saccades. It is generally assumed that visual stability is due to
      the process of remapping, in which retinotopically organized maps are updated to
      compensate for the retinal shifts caused by eye movements. Recent behavioral and
      ERP evidence suggests that visual attention is also remapped, but that it may
      still leave a residual retinotopic trace immediately after a saccade. The current
      study was designed to further examine electrophysiological evidence for such a
      retinotopic trace by recording ERPs elicited by stimuli that were presented
      immediately after a saccade (80 msec SOA). Participants were required to maintain
      attention at a specific location (and to memorize this location) while making a
      saccadic eye movement. Immediately after the saccade, a visual stimulus was
      briefly presented at either the attended location (the same spatiotopic
      location), a location that matched the attended location retinotopically (the
      same retinotopic location), or one of two control locations. ERP data revealed an
      enhanced P1 amplitude for the stimulus presented at the retinotopically matched
      location, but a significant attenuation for probes presented at the original
      attended location. These results are consistent with the hypothesis that
      visuospatial attention lingers in retinotopic coordinates immediately following
      gaze shifts. 

PMID- 23530899
TI  - Identification of a founder EPCAM deletion in Spanish Lynch syndrome families.
AB  - Germline deletions at the 3'-end of EPCAM have been involved in the etiology of
      Lynch syndrome (LS). The aim of this study was to characterize at the molecular
      level Spanish families harboring EPCAM deletions. Non-commercial multiplex
      ligation-dependent probe amplification (MLPA) probes and long-range polymerase
      chain reaction (PCR) amplification were used to characterize each deletion.
      Haplotyping was performed by analyzing eight microsatellite markers and five
      MSH2single nucleotide polymorphisms (SNPs). Methylation of MSH2 was analyzed by
      methylation specific-MLPA. Tumors diagnosed in seven Spanish families harboring
      EPCAM deletions were almost exclusively colorectal. Mosaicism in MSH2 methylation
      was observed in EPCAM deletion carrier samples, being average methylation levels
      higher in normal colon and colorectal tumors (27.6% and 31.1%), than in
      lymphocytes and oral mucosa (1.1% and 0.7%). Three families shared the deletion
      c.858 + 2568_*4596del, with a common haplotype comprising 9.9 Mb. In two families
      the novel EPCAM deletion c.858 + 2488_*7469del was identified. This study
      provides knowledge on the clinical and molecular characteristics of mosaic MSH2
      epimutations. The identification of an EPCAM founder mutation has useful
      implications for the molecular diagnosis of LS in Spain.

PMID- 23530900
TI  - Vulnerability of streams to legacy nitrate sources.
AB  - The influence of hydrogeologic setting on the susceptibility of streams to legacy
      nitrate was examined at seven study sites having a wide range of base flow index
      (BFI) values. BFI is the ratio of base flow to total streamflow volume. The
      portion of annual stream nitrate loads from base flow was strongly correlated
      with BFI. Furthermore, dissolved oxygen concentrations in streambed pore water
      were significantly higher in high BFI watersheds than in low BFI watersheds
      suggesting that geochemical conditions favor nitrate transport through the bed
      when BFI is high. Results from a groundwater-surface water interaction study at a
      high BFI watershed indicate that decades old nitrate-laden water is discharging
      to this stream. These findings indicate that high nitrate levels in this stream
      may be sustained for decades to come regardless of current practices. It is
      hypothesized that a first approximation of stream vulnerability to legacy
      nutrients may be made by geospatial analysis of watersheds with high nitrogen
      inputs and a strong connection to groundwater (e.g., high BFI).

PMID- 23530901
TI  - Hepatitis B virus in the Maghreb region: from epidemiology to prospective
      research.
AB  - Hepatitis B virus (HBV) represents an important health problem in the Maghreb
      countries, Algeria, Libya, Mauritania, Morocco and Tunisia, but no detailed
      synthesis of its epidemiology is available. In this review, we systematically
      searched for data about HBV in the Maghreb in peer-reviewed databases and
      included in our analysis works written in English and French, as well as
      institutional reports and regional conference meeting abstracts. We estimated
      national and regional prevalence of chronic HBV infection. In addition, we
      discuss molecular features of the viral strains circulating in the region. Data
      analysis suggests that in the Maghreb region HBs antigen carriage concerns 1.8
      4.9% of the population for an estimated number of 2.7 million persons. Genotype
      D, subtype D7, is predominant and mutations in the precore region of HBV genome
      are highly prevalent. This epidemiological situation requires obviously
      widespread active interventions for prevention and control. In addition, anti
      hepatitis B vaccination programme should be applied with the utmost discipline in
      the five countries considered in this present review. This systematic review
      will, hopefully, increase knowledge at disposal of Public Health authorities,
      enabling better resource allocation and healthcare delivery. The present
      synthesis intends to stimulate policies aiming at preventing the spread of HBV,
      keeping in mind that eradication of the virus from Maghrebi populations should be
      the ultimate objective of Public Health authorities.

PMID- 23530902
TI  - The type II secretion system (Xcp) of Pseudomonas putida is active and involved
      in the secretion of phosphatases.
AB  - The genome of the Gram-negative bacterium Pseudomonas putida harbours a complete
      set of xcp genes for a type II protein secretion system (T2SS). This study shows
      that expression of these genes is induced under inorganic phosphate (Pi )
      limitation and that the system enables the utilization of various organic
      phosphate sources. A phosphatase of the PhoX family, previously designated UxpB,
      was identified, which was produced under low Pi conditions and transported across
      the cell envelope in an Xcp-dependent manner demonstrating that the xcp genes
      encode an active T2SS. The signal sequence of UxpB contains a twin-arginine
      translocation (Tat) motif as well as a lipobox, and both processing by leader
      peptidase II and Tat dependency were experimentally confirmed. Two different tat
      gene clusters were detected in the P. putida genome, of which one, named tat-1,
      is located adjacent to the uxpB and xcp genes. Both Tat systems appeared to be
      capable of transporting the UxpB protein. However, expression of the tat-1 genes
      was strongly induced by low Pi levels, indicating a function of this system in
      survival during Pi starvation. 

PMID- 23530903
TI  - Ultrasound real-time elastography can predict malignancy in BI-RADS(r)-US 3
      lesions.
AB  - BACKGROUND: Lesions of the breast that are classified BI-RADS(r)-US 3 by
      ultrasound are probably benign and observation is recommended, although
      malignancy may occasionally occur. In our study, we focus exclusively on BI
      RADS(r)-US 3 lesions and hypothesize that sonoelastography as an adjunct to
      conventional ultrasound can identify a high-risk-group and a low-risk-group
      within these patients. METHODS: A group of 177 breast lesions that were
      classified BI-RADS(r)-US 3 were additionally examined with real-time
      sonoelastography. Elastograms were evaluated according to the Tsukuba Elasticity
      Score. Pretest and posttest probability of disease (POD), sensitivity (SE),
      specificity (SP), positive (PPV) and negative predictive values (NPV) and
      likelihood-ratios (LR) were calculated. Furthermore, we analyzed the false
      negative and false-positive cases and performed a model calculation to determine
      how elastography could affect the proceedings in population screening. RESULTS:
      In our collection of BI-RADS(r)-US 3 cases there were 169 benign and eight
      malignant lesions. The pretest POD was 4.5% (95% confidence interval (CI): 2.1
      9.0). In patients with a suspicious elastogram (high-risk group), the posttest
      POD was significantly higher (13.2%, p = 0.041) and the positive LR was 3.2 (95%
      CI: 1.7-5.9). With a benign elastogram (low-risk group), the posttest POD
      decreased to 2.2%. SE, SP, PPV and NPV for sonoelastography in BI-RADS(r)-US 3
      lesions were 62.5% (95% CI: 25.9-89.8), 80.5% (95% CI: 73.5-86.0), 13.2% (95% CI:
      5.0-28.9) and 97.8% (95% CI: 93.3-99.4), respectively. CONCLUSIONS:
      Sonoelastography yields additional diagnostic information in the evaluation of BI
      RADS(r)-US 3 lesions of the breast. The examiner can identify a low-risk group
      that can be vigilantly observed and a high-risk group that should receive
      immediate biopsy due to an elevated breast cancer risk.

PMID- 23530904
TI  - Clinically verrucous and histologically discohesive melanoma. A case report with
      dermoscopic and immunohistochemical observations.

PMID- 23530905
TI  - Effects of chain length of an amphipathic polypeptide carrying the repeated amino
      acid sequence (LETLAKA)(n) on alpha-helix and fibrous assembly formation.
AB  - Polypeptide alpha3 (21 residues), with three repeats of a seven-amino-acid
      sequence (LETLAKA)(3), forms an amphipathic alpha-helix and a long fibrous
      assembly. Here, we investigated the ability of alpha3-series polypeptides (with
      14-42 residues) of various chain lengths to form alpha-helices and fibrous
      assemblies. Polypeptide alpha2 (14 residues), with two same-sequence repeats, did
      not form an alpha-helix, but polypeptide alpha2L (15 residues; alpha2 with one
      additional leucine residue on its carboxyl terminal) did form an alpha-helix and
      fibrous assembly. Fibrous assembly formation was associated with polypeptides at
      least as long as polypeptide alpha2L and with five leucine residues, indicating
      that the C-terminal leucine has a critical element for stabilization of alpha
      helix and fibril formation. In contrast, polypeptides alpha5 (35 residues) and
      alpha6 (42 residues) aggregated easily, although they formed alpha-helices. A 15
      35-residue chain was required for fibrous assembly formation. Electron microscopy
      and X-ray fiber diffraction showed that the thinnest fibrous assemblies of
      polypeptides were about 20 A and had periodicities coincident with the length of
      the alpha-helix in a longitudinal direction. These results indicated that the
      alpha-helix structures were orientated along the fibrous axis and assembled into
      a bundle. Furthermore, the width and length of fibrous assemblies changed with
      changes in the pH value, resulting in variations in the charged states of the
      residues. Our results suggest that the formation of fibrous assemblies of
      amphipathic alpha-helices is due to the assembly of bundles via the hydrophobic
      faces of the helices and extension with hydrophobic noncovalent bonds containing
      a leucine.

PMID- 23530906
TI  - Type 3 finger length pattern is associated with total knee replacements due to
      osteoarthritis but not with hip replacements or hand osteoarthritis in the
      elderly: the AGES-Reykjavik study.
AB  - BACKGROUND: Recent case-control studies have shown an association between type 3
      finger length pattern (longer ring finger than index finger) and knee
      osteoarthritis. This large cross-sectional study tests the hypothesis that the
      type 3 pattern is associated with total joint replacements due to osteoarthritis
      in a large population based study. METHODS: Finger length ratios were assessed
      visually on 5170 hand photographs (2975 females, 2195 males, mean age 76). In
      this population-based multidisciplinary study of aging in Reykjavik, Iceland, the
      prevalence of osteoarthritis associated total knee replacements was 223(4.3%) and
      total hip replacements 316(6.1%). We then performed a binary logistic regression
      analysis for total knee replacements and total hip replacements, including finger
      length patterns, osteoarthritis at other sites and other variables with possible
      association to osteoarthritis such as age, BMI and bone mineral density of the
      spine. RESULTS: The prevalence of the type 3 pattern was 50% (43% in females, 58%
      in males). The regression analysis revealed an odds ratio for total knee
      replacements of 1.65 (1.24-2.2) p = 0.0007, in the type 3 finger pattern group,
      similar in both genders. This association was independent of the associations we
      have previously reported between total knee replacements and BMI and the presence
      of hand osteoarthritis. No association was seen between finger length patterns
      and total hip replacements. CONCLUSION: Finger length patterns read from digital
      photographs in this large study confirm previous radiographic observations with
      significant associations between the type 3 pattern and total knee replacements
      but not total hip replacements in both genders in this elderly group.

PMID- 23530908
TI  - Craniopharyngiomas with a mixed histological pattern: the missing link to the
      intriguing pathogenesis of adamantinomatous and squamous-papillary varieties?

PMID- 23530907
TI  - Pertussis re-emergence in the post-vaccination era.
AB  - BACKGROUND: Resurgence of pertussis in the post-vaccination era has been reported
      in Western countries. A shift of cases from school-age children to adolescents,
      adults and children under 1 year of age has been described in the last decade,
      and mortality rates in infants are still sustained. We aimed to review and
      discuss the possible vaccination strategies which can be adopted in order to
      improve the pertussis control, by searches of Pubmed, and websites of US and
      European Centers for Disease Control and Prevention, between 1st January 2002,
      and 1st March 2013. DISCUSSION: The following vaccination strategies have been
      retrieved and analysed: the cocooning strategy, the immunization of pregnant
      women and newborns, vaccination programs for preschool children, adolescents,
      adults and health-care workers. Cost-effectiveness studies provide some
      contrasting data, mainly supporting both maternal vaccination and cocooning.
      Adolescent and/or adult vaccination seems to be cost-effective, however data from
      observational studies suggest that this vaccination strategy, used alone, leads
      to a reduced pertussis burden globally, but does not affect the disease incidence
      in infants. Moreover, substantial logistical and economic difficulties have to be
      overcome to vaccinate the largest number of individuals. SUMMARY: The
      simultaneous use of more than one strategy, including cocooning strategy plus
      vaccination of adolescents and adults, seems to be the most reasonable preventive
      measure. The development of new highly immunogenic and efficacious pertussis
      vaccines continues to be a primary objective for the control of pertussis.

PMID- 23530909
TI  - Immunohistochemical expression of glypican-3 in pediatric tumors: an analysis of
      414 cases.
AB  - Glypican-3 (GPC3) is a proteoglycan thought to play an important role during
      development. Germline GPC3 mutations are seen in the rare Simpson-Golabi-Behmel
      syndrome (SGBS), which predisposes patients to Wilms tumor, hepatoblastoma, and
      neuroblastoma. While numerous adult tumors have been evaluated by
      immunohistochemistry for GPC3, no comprehensive assessment has been done in
      pediatric tumors. We therefore investigated GPC3 expression in 143 pediatric
      central nervous system (CNS) tumors and 271 non-CNS tumors. Among non-CNS tumors,
      GPC3 expression was seen in 9/9 (100%) hepatoblastomas, 4/6 (67%) malignant
      rhabdoid tumors, 5/13 (38%) Wilms tumors, 11/37 (30%) alveolar rhabdomyosarcomas,
      and 8/45 (18%) embryonal rhabdomyosarcomas. All 136 neuroblastomas, 14 Ewing
      sarcoma/primitive neuroectodermal tumors, and 11 synovial sarcomas were
      immunonegative for GPC3. Among CNS tumors, GPC3 had restricted expression, with
      positivity in 6/6 (100%) atypical teratoid rhabdoid tumors and 1/4 (25%)
      craniopharyngiomas. The remaining 136 CNS tumors-23 medulloblastomas, 21
      pilocytic astrocytomas, 13 gangliogliomas, 12 ependymomas, 12 glioblastomas, 11
      choroid plexus neoplasms, 10 diffuse astrocytomas (grade II/III), 10 meningiomas,
      8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 3
      craniopharyngiomas, 3 germinomas, and 2 neurocytomas-were entirely negative for
      GPC3. These results showed GPC3 positivity in a number of non-CNS tumors, with no
      consistent discrimination between tumors that were or were not associated with
      SGBS. Within the CNS, GPC3 positivity was limited to a small subset of CNS
      neoplasms and may thus serve as a useful positive diagnostic biomarker (P <
      0.0001) in addition to negative INI1/BAF47/SMARCB1 staining to differentiate
      atypical teratoid rhabdoid tumors from other high-grade pediatric brain tumors.

PMID- 23530910
TI  - Genes associated with the cis-regulatory functions of intragenic LINE-1 elements.
AB  - BACKGROUND: Thousands of intragenic long interspersed element 1 sequences (LINE-1
      elements or L1s) reside within genes. These intragenic L1 sequences are conserved
      and regulate the expression of their host genes. When L1 methylation is
      decreased, either through chemical induction or in cancer, the intragenic L1
      transcription is increased. The resulting L1 mRNAs form RISC complexes with pre
      mRNA to degrade the complementary mRNA. In this study, we screened for genes that
      are involved in intragenic L1 regulation networks. RESULTS: Genes containing L1s
      were obtained from L1Base (http://l1base.molgen.mpg.de). The expression profiles
      of 205 genes in 516 gene knockdown experiments were obtained from the Gene
      Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo). The expression levels
      of the genes with and without L1s were compared using Pearson's chi-squared test.
      After a permutation based statistical analysis and a multiple hypothesis testing,
      73 genes were found to induce significant regulatory changes (upregulation and/or
      downregulation) in genes with L1s. In detail, 5 genes were found to induce both
      the upregulation and downregulation of genes with L1s, whereas 27 and 37 genes
      induced the downregulation and upregulation, respectively, of genes with L1s.
      These regulations sometimes differed depending on the cell type and the
      orientation of the intragenic L1s. Moreover, the siRNA-regulating genes
      containing L1s possess a variety of molecular functions, are responsible for many
      cellular phenotypes and are associated with a number of diseases. CONCLUSIONS:
      Cells use intragenic L1s as cis-regulatory elements within gene bodies to
      modulate gene expression. There may be several mechanisms by which L1s mediate
      gene expression. Intragenic L1s may be involved in the regulation of several
      biological processes, including DNA damage and repair, inflammation, immune
      function, embryogenesis, cell differentiation, cellular response to external
      stimuli and hormonal responses. Furthermore, in addition to cancer, intragenic
      L1s may alter gene expression in a variety of diseases and abnormalities.

PMID- 23530911
TI  - Evaluation of the relationship between arterial blood pressure, aortic stiffness
      and serum endothelin-1 levels in patients with essential hypertension.
AB  - This study has attempted to evaluate the relationship between aortic stiffness,
      blood pressure (BP) and serum endothelin-1 (ET-1) levels in patients with
      essential HT. Totally 152 subjects, consisting of 103 patients diagnosed with HT
      at least 1 year previously and 49 healthy individuals, were enrolled in this
      study. They were subdivided, on the basis of BP measurements made at home, into
      three groups as the hypertensives with dysregulated BP (n = 56), the
      hypertensives with regulated BP (n = 47) and the normotensive controls (n = 49).
      Statistically significant differences were observed between the three groups with
      respect to aortic elasticity parameters (p < 0.01 for aortic strain, aortic
      distensibility and aortic stiffness). Serum ET-1 levels in the three groups were
      similar (p = 0.101), but a significant correlation was observed between the ET-1
      values and the aortic elasticity parameters (p = 0.004). Alteration of the aortic
      elasticity parameters in patients with HT not only correlates with the serum ET-1
      levels indicating endothelial dysfunction but also gives direct clues about
      status of BP regulation. 

PMID- 23530912
TI  - Gastroesophageal reflux disease and its association with bronchiolitis obliterans
      syndrome in allogeneic hematopoietic stem cell transplant recipients.
AB  - OBJECTIVES: Bronchiolitis obliterans syndrome is a significant postallogeneic
      hematopoietic stem cell transplant problem. Recent data in lung transplant
      patients suggest an association with gastroesophageal reflux disease and
      bronchiolitis obliterans syndrome. We studied posthematopoietic stem cell
      transplant patients with bronchiolitis obliterans syndrome for gastroesophageal
      reflux disease and its response to a proton pump inhibitor. MATERIALS AND
      METHODS: Seven postallogeneic hematopoietic stem cell transplant patients with
      bronchiolitis obliterans syndrome were studied. Gastroesophageal reflux disease
      was assessed by 24-hour pH monitoring with a Bravo catheter-free radio pH
      capsule. Patients with positive gastroesophageal reflux disease were started on
      omeprazole. Pretreatment and posttreatment pulmonary function tests were done at
      3-month intervals. RESULTS: Of 7 patients, 5 had positive results for
      gastroesophageal reflux disease (71%). Omeprazole had a disease-stabilizing
      effect on the patients' pulmonary function tests. CONCLUSIONS: Our study shows a
      significant association between bronchiolitis obliterans syndrome and
      gastroesophageal reflux disease in postallogeneic hematopoietic stem cell
      transplant patients. Use of omeprazole may have a disease-stabilizing effect in
      short-term follow-up.

PMID- 23530914
TI  - Understanding the role of representations of human-leopard conflict in Mumbai
      through media-content analysis.
AB  - Attempts to minimize the effects of human-wildlife conflict (HWC) on conservation
      goals require an understanding of the mechanisms by which such conflicts are
      caused and sustained. This necessitates looking beyond the natural sciences to
      the human dimensions of wildlife management. Public dissemination of information
      regarding HWC occurs largely through the mass media. We conducted a content
      analysis of print media articles on human-leopard conflict in Mumbai, India. We
      sought to understand the framing of HWC and the changes in media coverage over a
      10-year period (2001-2011) during which a large number of attacks on people prior
      to 2005 were followed by a program of trapping and relocation. After 2005, when
      there was a decrease in the level of conflict, the tone of English-language media
      reports changed. The perpetrator framing was over 5 times more likely before
      2005, whereas a neutral framing was twice as likely after 2005. English-language
      and non-English-language print media differed significantly in their framing of
      HWC and in the kinds of solutions advocated. Our results also suggest the print
      mass media in Mumbai could be an influential conduit for content that diminishes
      HWC. These media outlets seem attentive to human-leopard conflict, capable of
      correcting erroneous perceptions and facilitating mitigation and effective
      management. We believe better contact and mutual understanding between
      conservation professionals and the mass media could be an important component of
      managing HWC. We further suggest that in such interactions conservation
      professionals need to be aware of cultural and linguistic differences in
      reporting within the country.

PMID- 23530916
TI  - Accessibility of blood affects the attractiveness of cattle to horn flies.
AB  - The burden of infestation of the horn fly, Haematobia irritans (Linnaeus)
      (Diptera: Muscidae), differs among bovines within the same herd. We hypothesized
      that these differences might be related to the epidermal thickness of the cattle
      and the blood intake capacity of the fly. Results showed that dark animals
      carried more flies and had a thinner epidermis than light-coloured animals, which
      was consistent with the greater haemoglobin content found in flies caught on
      darker cattle. Similarly, epidermal thickness increased with body weight, whereas
      haemoglobin content decreased. Overall, we suggest that accessibility of blood is
      a factor that partially explains cattle attractiveness to flies. 

PMID- 23530915
TI  - Trans-packaging of human immunodeficiency virus type 1 genome into Gag virus-like
      particles in Saccharomyces cerevisiae.
AB  - BACKGROUND: Yeast is recognized as a generally safe microorganism and is utilized
      for the production of pharmaceutical products, including vaccines. We previously
      showed that expression of human immunodeficiency virus type 1 (HIV-1) Gag protein
      in Saccharomyces cerevisiae spheroplasts released Gag virus-like particles (VLPs)
      extracellularly, suggesting that the production system could be used in vaccine
      development. In this study, we further establish HIV-1 genome packaging into Gag
      VLPs in a yeast cell system. RESULTS: The nearly full-length HIV-1 genome
      containing the entire 5' long terminal repeat, U3-R-U5, did not transcribe gag
      mRNA in yeast. Co-expression of HIV-1 Tat, a transcription activator, did not
      support the transcription. When the HIV-1 promoter U3 was replaced with the
      promoter for the yeast glyceraldehyde-3-phosphate dehydrogenase gene, gag mRNA
      transcription was restored, but no Gag protein expression was observed. Co
      expression of HIV-1 Rev, a factor that facilitates nuclear export of gag mRNA,
      did not support the protein synthesis. Progressive deletions of R-U5 and its
      downstream stem-loop-rich region (SL) to the gag start ATG codon restored Gag
      protein expression, suggesting that a highly structured noncoding RNA generated
      from the R-U5-SL region had an inhibitory effect on gag mRNA translation. When a
      plasmid containing the HIV-1 genome with the R-U5-SL region was coexpressed with
      an expression plasmid for Gag protein, the HIV-1 genomic RNA was transcribed and
      incorporated into Gag VLPs formed by Gag protein assembly, indicative of the
      trans-packaging of HIV-1 genomic RNA into Gag VLPs in a yeast cell system. The
      concentration of HIV-1 genomic RNA in Gag VLPs released from yeast was
      approximately 500-fold higher than that in yeast cytoplasm. The deletion of R-U5
      to the gag gene resulted in the failure of HIV-1 RNA packaging into Gag VLPs,
      indicating that the packaging signal of HIV-1 genomic RNA present in the R-U5 to
      gag region functions similarly in yeast cells. CONCLUSIONS: Our data indicate
      that selective trans-packaging of HIV-1 genomic RNA into Gag VLPs occurs in a
      yeast cell system, analogous to a mammalian cell system, suggesting that yeast
      may provide an alternative packaging system for lentiviral RNA.

PMID- 23530917
TI  - The actin-based machinery of Trichomonas vaginalis mediates flagellate-amoeboid
      transition and migration across host tissue.
AB  - Trichomonas vaginalis is the most widespread non-viral pathogen of the human
      urogenital tract, infecting ~ 3% of the world's population annually. At the onset
      of infection the protist changes morphology within minutes: the flagellated free
      swimming cell converts into the amoeboid-adherent stage. The molecular machinery
      of this process is not well studied, but is thought to involve actin
      reorganization. We have characterized amoeboid transition, focusing in particular
      on TvFim1, the only expressed protein of the fimbrin family in Trichomonas.
      Addition of TvFim1 to actin polymerization assays increases the speed of actin
      filament assembly and results in bundling of F-actin in a parallel and anti
      parallel manner. Upon contact with vaginal epithelial cells, the otherwise
      diffuse localization of actin and TvFim1 changes dramatically. In the amoeboid
      TvFim1 associates with fibrous actin bundles and concentrates at protrusive
      structures opposing the trailing ends of the gliding amoeboid form and rapidly
      redistributes together with actin to form distinct clusters. Live cell imaging
      demonstrates that Trichomonas amoeboid stages do not just adhere to host tissue,
      rather they actively migrate across human epithelial cells. They do so in a
      concerted manner, with an average speed of 20 MUm min(-1) and often using their
      flagella and apical tip as the leading edge. 

PMID- 23530918
TI  - Transarterial embolization as neo-adjuvant therapy pretransplantation in patients
      with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Neo-adjuvant transarterial therapies are commonly used for
      patients with HCC in the waiting list for liver transplantation (LT) to delay
      tumour progression, however, their effectiveness is not well-established. We
      studied the effect of pre-LT transarterial therapies on post-LT HCC recurrence,
      using the explanted liver histology to assess therapeutic efficacy and the
      predictors of response to these therapies. METHODS: We included 150 consecutive
      patients from our prospectively compiled database, listed for liver
      transplantation using the Milan criteria. Transarterial embolization without
      chemotherapeutic agents was the transarterial therapy used as standard of care.
      PVA particles were the embolizing agent of choice. RESULTS: Sixty-seven (45%)
      patients had TAE as bridging therapy to liver transplantation, of which 60 were
      transplanted after 2001. The majority of patients (36, 54%) had partial tumour
      necrosis after transarterial therapy, whereas 22 (33%) had complete tumour
      necrosis and 9 (13%) had no necrosis. HCC post-transplant recurrence was
      independently associated with no neo-adjuvant transarterial therapy (OR 5.395,
      95% CI 1.289-22.577; P = 0.021) and the total radiological size of HCC nodules
      (OR 1.037, 95% CI 1.006-1.069; P = 0.020). CONCLUSIONS: Pre-transplant TAE with
      the more permanently occluding PVA particles significantly reduces post
      transplant HCC recurrence in patients within the Milan criteria.

PMID- 23530919
TI  - A pilot study examining short-term changes in bone mineral density among class 3
      obese users of depot-medroxyprogesterone acetate.
AB  - OBJECTIVE: To examine changes in lumbar spine-bone mineral density (LS-BMD) among
      normal weight (body mass index [BMI] = 18.5-24.9 kg/m(2)), Class 1-2 obese (BMI =
      30-39.9 kg/m(2)), and Class 3 obese (BMI >= 40 kg/m(2)) women utilising depot
      medroxyprogesterone acetate (DMPA). METHODS: Five normal-weight, five Class 1-2
      obese, and five Class 3 obese women received subcutaneous injections of DMPA-SC
      at baseline and 12 weeks later. Dual Energy X-ray Absorptiometry (DEXA) scans
      were performed at baseline and 18 weeks after the first injection for
      determination of LS-BMD and analysis of fat content. Bimonthly oestradiol (E2)
      levels were measured by immunoassay methods for 26 weeks. RESULTS: There were no
      significant demographic or LS-BMD differences among the three BMI groups.
      Significant differences at baseline were as expected among the three groups with
      respect to BMI and associated parameters (mean % total body fat, absolute fat,
      and weight). When used as their own controls, significant changes in LS-BMD, %
      body fat and absolute fat determined by DEXA occurred among all three BMI strata.
      Class 1-2 obese and Class 3 obese women were more likely to experience E2
      fluctuations, but short-term changes in LS-BMD were similar. CONCLUSIONS: DMPA-SC
      administration affects L-spine bone health similarly regardless of BMI status.

PMID- 23530920
TI  - Analysing diversity and community structures using PCR-RFLP: a new software
      application.
AB  - Restriction fragment length polymorphism tools is an R application which supports
      a complete workflow of polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP), dealing with the problems which accompany analysis when
      PCR-RFLP is used in diversity studies. Large numbers of different RFLP samples
      obtained from multiple electrophoresis runs might lead to limitations or
      misidentifications due to the need for band matching in most existing software
      applications. Due to the common problem of variation in the density of bands
      (i.e. distances between bands or visual intensity) in the electropherograms, it
      is desirable to have options for handling samples with uncertain or faint bands.
      As a further step in the workflow, scientists often use DNA sequencing to
      identify individual genotypes, so that the use of specific software to combine
      these tasks might be helpful. With this background, we here present an
      application that supports a complete workflow, starting with the analysis of
      single species samples by PCR-RFLP, to PCR-RFLP genotype identification based on
      a reference data set and DNA sequencing followed by similarity analysis.
      RFLPtools is a freely available, platform-independent application which provides
      analysis functions for DNA fragment molecular weights (e.g. by RFLP analysis),
      including similarity calculations without the need for band matching. As it is
      written for the statistical software R, other statistical analyses might also be
      easily applied.

PMID- 23530921
TI  - Attention-modulated alpha-band oscillations protect against intrusion of
      irrelevant information.
AB  - Combining high-density scalp EEG recordings with a sensitive analog measure of
      STM's fidelity, we characterized the temporal dynamics of intentional ignoring
      and related those dynamics to the intrusion of task-irrelevant information. On
      each trial of the task, two study Gabors were briefly presented in succession. A
      green or red disc preceding each Gabor signified whether that Gabor should be
      remembered or ignored, respectively. With cue-stimulus intervals of 300, 600, or
      900 msec presented in separate sessions, we found that the onset of posterior,
      prestimulus alpha oscillations varied with the length of the interval. Although
      stimulus onset time was entirely predictable, the longer the cue-stimulus
      interval, the earlier the increase in prestimulus alpha power. However, the alpha
      band modulation was not simply locked to the cue offset. The temporal envelopes
      of posterior alpha-band modulation were strikingly similar for both cued
      attending and cued ignoring and differed only in magnitude. This similarity
      suggests that cued attending includes suppression of task-irrelevant, spatial
      processing. Supporting the view that alpha-band oscillations represent
      inhibition, our graded measure of recall revealed that, when the stimulus to be
      ignored appears second in the sequence, peristimulus alpha power predicted the
      degree to which that irrelevant stimulus distorted subsequent recall of the
      stimulus that was to be remembered. These results demonstrate that timely
      deployment of attention-related alpha-band oscillations can aid STM by filtering
      out task-irrelevant information. 

PMID- 23530922
TI  - Negative BOLD response in the hippocampus during short-term spatial memory
      retrieval.
AB  - A parieto-medial temporal pathway is thought to underlie spatial navigation in
      humans. fMRI was used to assess the role of this pathway, including the
      hippocampus, in the cognitive processes likely to underlie navigation based on
      environmental cues. Participants completed a short-term spatial memory task in
      virtual space, which required no navigation but involved the recognition of a
      target location from a foil location based on environmental landmarks. The
      results showed that spatial memory retrieval based on environmental landmarks was
      indeed associated with increased signal in regions of the parieto-medial temporal
      pathway, including the superior parietal cortex, the retrosplenial cortex, and
      the lingual gyrus. However, the hippocampus demonstrated a signal decrease below
      the fixation baseline during landmark-based retrieval, whereas there was no
      signal change from baseline during retrieval based on viewer position. In a
      discussion of the origins of such negative BOLD response in the hippocampus, we
      consider both a suppression of default activity and an increase in activity
      without a corresponding boost in CBF as possible mechanisms. 

PMID- 23530924
TI  - Systematic reviews of surgical procedures in children: quantity, coverage and
      quality.
AB  - AIM: Systematic reviews have the potential to map those areas where children are
      under-represented in surgical research. We aimed to describe and evaluate the
      quantity, coverage and the quality of conduct and reporting of systematic reviews
      of surgical procedures in children. METHODS: We searched four biomedical
      databases, a systematic review register, reference lists and conducted hand
      searching to identify relevant reviews. Two reviewers worked independently to
      critically appraise included studies and abstract data. We assessed reporting
      quality using the preferred reporting items for systematic reviews and meta
      analysis statement and methodological quality using the Assessment of Multiple
      SysTemAtic Reviews tool. RESULTS: Fifteen systematic reviews were identified,
      representing 0.01% of all paediatric surgical citations in MEDLINE and Embase.
      Thirteen of the reviews were Cochrane reviews, and most reviews (12/15) addressed
      subspecialty interests such as otorhinolaryngology. The median number of included
      trials per systematic review was four (interquartile range 1 to 9.5), the median
      number of primary outcomes was 5.5 (interquartile range 3.5 to 7.5). In general,
      reporting and methodological quality was good although there were several
      omissions, particularly around completeness of reporting of statistical methods
      used, and utilisation of quality assessments in analyses. Outcomes were often not
      clearly defined and descriptions of procedures lacked sufficient detail to
      determine the similarities and differences among surgical procedures within the
      contributing trials. CONCLUSION: Systematic reviews of surgical procedures in
      children are rarely published. To improve the evidence base and guide research
      agendas, more systematic reviews should be conducted, using standard guidelines
      for conduct and reporting.

PMID- 23530923
TI  - Effects of working memory demand on neural mechanisms of motor response selection
      and control.
AB  - Inhibitory control commonly recruits a number of frontal regions: pre
      supplementary motor area (pre-SMA), frontal eye fields (FEFs), and right
      lateralized posterior inferior frontal gyrus (IFG), dorsal anterior insula (DAI),
      dorsolateral prefrontal cortex (DLPFC), and inferior frontal junction (IFJ).
      These regions may directly implement inhibitory motor control or may be more
      generally involved in executive control functions. Two go/no-go tasks were used
      to distinguish regions specifically recruited for inhibition from those that
      additionally show increased activity with working memory demand. The pre-SMA and
      IFG were recruited for inhibition in both tasks and did not have greater
      activation for working memory demand on no-go trials, consistent with a role in
      inhibitory control. Activation in pre-SMA also responded to response selection
      demand and was increased with working memory on go trials specifically. The
      bilateral FEF and right DAI were commonly active for no-go trials. The FEF was
      also recruited to a greater degree with working memory demand on go trials and
      may bias top-down information when stimulus-response mappings change. The DAI,
      additionally responded to increased working memory demand on both go and no-go
      trials and may be involved in accessing sustained task information, alerting, or
      autonomic changes when cognitive demands increase. DLPFC activation was
      consistent with a role in working memory retrieval on both go and no-go trials.
      The inferior frontal junction, on the other hand, had greater activation with
      working memory specifically for no-go trials and may detect salient stimuli when
      the task requires frequent updating of working memory representations. 

PMID- 23530925
TI  - Systematic kidney biopsies after acute allograft pyelonephritis.
AB  - OBJECTIVES: Scarce data exist regarding the effect of acute graft pyelonephritis
      on kidney histology after a kidney transplant. This study sought to assess the
      kidney histology at 1 month, and kidney function at 1 year, after acute graft
      pyelonephritis in kidney transplant patients. MATERIALS AND METHODS: All kidney
      transplant patients with acute graft pyelonephritis between October 2006, and
      December 2008, underwent a kidney biopsy 1 month later (n=28). Histologic
      findings were compared with those observed in a control group (n=28) who
      underwent a protocol kidney biopsy at 1 year posttransplant and did not present
      with acute graft pyelonephritis. Patients were matched according to age, sex, and
      immunosuppressive regimen. RESULTS: Kidney function was impaired by the acute
      graft pyelonephritis episodes at the time of biopsy. In 40% of patients, the
      estimated glomerular filtration rate did not return to baseline by 1 month after
      acute graft pyelonephritis and remained impaired thereafter. Three patients had
      features of acute rejection. Tubulitis was seen more frequently in the acute
      graft pyelonephritis group, especially in patients in whom estimated glomerular
      filtration rate did not completely recover by 1 month after acute graft
      pyelonephritis. Patients with acute graft pyelonephritis who had inflammatory
      infiltrate of > 20% 1 month after acute graft pyelonephritis had worse kidney
      function 1 year later. CONCLUSIONS: After transplant, when kidney function
      remains impaired 1 month after acute graft pyelonephritis, kidney biopsies
      allowed graft rejection diagnosis and predicted kidney function recovery.

PMID- 23530926
TI  - In vivo degradation and elimination of injectable ricinoleic acid-based
      poly(ester-anhydride).
AB  - The in vivo degradation and elimination after subcutaneous implantation of
      injectable p(SA-RA) 3:7 copolymer in rats, followed by characterization of the
      polymer matrix composition during hydrolysis and erosion, is reported. Major
      chemical changes were observed during the first few days post implantation, the
      anhydride bonds hydrolyzed along with about 45% weight loss and a significant
      decrease in the molecular weight. 1H NMR spectral analysis was used to determine
      the structures and content of ricinoleic acid containing oligomeric chains
      present in the degraded polymer. The polymer degrades into ester oligomers of 2-4
      ricinoleic acid units which further degrade to ricinoleic acid, a natural fatty
      acid. The polymer hydrolytic degradation process fit the in vitro degradation
      process.

PMID- 23530928
TI  - Dysembryoplastic neuroepithelial tumor, a pure glial tumor? Immunohistochemical
      and morphometric studies.
AB  - Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal tumor,
      occurring in children and adolescents, typically associated with drug-resistant
      partial seizures. Pathologically, DNT is characterized by a specific glioneuronal
      element that is comprised of oligodendroglia-like cells (OLC) and floating
      neurons. The definition of DNT is currently controversial and the incidence of
      DNT varies among institutions. In this study we characterize the morphologic
      profiles of OLC and floating neurons by performing immunohistochemical and
      morphometric studies on seven cases of a simple form of DNT. While a majority of
      OLC was positive for oligodendrocyte transcription factor 2 (Olig2), only
      floating neurons and a few small cells were positive for neuronal nuclear
      antigens (NeuN). Double immunofluorescence studies revealed co-localization of
      Olig2 and galectin 3 in OLC, but no co-localization of Olig2 and NeuN. The
      distribution pattern of NeuN-positive nuclei within the tumor tissue was not
      different from that in the adjacent neural tissue. A section cut perpendicular to
      the cortex stained with NeuN showed a continuous laminar arrangement with the
      adjacent cortex. Densities of NeuN-positive nuclei from tumors embedded in the
      white matter were significantly lower than those from tumors in the gray matter.
      Our results suggest that the NeuN-positive small and large cells observed within
      the specific glioneuronal element are in fact entrapped granular and pyramidal
      cells within the cortex and that OLCs are essentially glial and not neuronal in
      nature. DNT is thus a pure glial tumor rather than a glioneuronal tumor, that is,
      the equivalent of non-infiltrating oligodendroglioma, grade I. 

PMID- 23530927
TI  - Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury
      on skeletal muscle in murine hindlimb.
AB  - BACKGROUND: Studies have shown that ischemia-reperfusion (I/R) produces free
      radicals leading to lipid peroxidation and damage to skeletal muscle. The
      purposes of this study were 1) to assess the histological findings of
      gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model
      mice, 2) to histologically analyze whether a single pretreatment of edaravone
      inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the
      effect of oxidative stress on these muscles. METHODS: C57BL6 mice were divided in
      two groups, with one group receiving 3 mg/kg intraperitoneal injections of
      edaravone (I/R + Ed group) and the other group receiving an identical amount of
      saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2
      pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This
      drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway,
      in addition to having potent antioxidant effects against ischemia reperfusion.
      The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72
      hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were
      removed for histological evaluation and biochemical analysis. RESULTS: This model
      of I/R injury was highly reproducible in histologic muscle damage. In the
      histologic damage score, the mean muscle fibers and inflammatory cell
      infiltration in the I/R + Ed group were significantly less than the corresponding
      values of observed in the I/R group. Thus, pretreatment with edaravone was
      observed to have a protective effect on muscle damage after a period of I/R in
      mice. In addition, the mean muscle injury score in the I/R + Ed group was also
      significantly less than the I/R group. In the I/R + Ed group, the mean
      malondialdehyde (MDA) level was lower than in the I/R group and western-blotting
      revealed that edaravone pretreatment decreased the level of inducible nitric
      oxide synthase (iNOS) expression. CONCLUSIONS: Edaravone was found to have a
      protective effect against I/R injury by directly inhibiting lipid peroxidation of
      the myocyte by free radicals in skeletal muscles and may also reduce the
      secondary edema and inflammatory infiltration incidence of oxidative stress on
      tissue.

PMID- 23530929
TI  - Retinoic acid-elicited RARalpha/RXRalpha signaling attenuates Abeta production by
      directly inhibiting gamma-secretase-mediated cleavage of amyloid precursor
      protein.
AB  - Retinoic acid (RA)-elicited signaling has been shown to play critical roles in
      development, organogenesis, and the immune response. RA regulates expression of
      Alzheimer's disease (AD)-related genes and attenuates amyloid pathology in a
      transgenic mouse model. In this study, we investigated whether RA can suppress
      the production of amyloid-beta (Abeta) through direct inhibition of gamma
      secretase activity. We report that RA treatment of cells results in significant
      inhibition of gamma-secretase-mediated processing of the amyloid precursor
      protein C-terminal fragment APP-C99, compared with DMSO-treated controls. RA
      elicited signaling was found to significantly increase accumulation of APP-C99
      and decrease production of secreted Abeta40. In addition, RA-induced inhibition
      of gamma-secretase activity was found to be mediated through significant
      activation of extracellular signal-regulated kinases (ERK1/2). Treatment of cells
      with the specific ERK inhibitor PD98059 completely abolished RA-mediated
      inhibition of gamma-secretase. Consistent with these findings, RA was observed to
      inhibit secretase-mediated proteolysis of full-length APP. Finally, we have
      established that RA inhibits gamma-secretase through nuclear retinoic acid
      receptor-alpha (RARalpha) and retinoid X receptor-alpha (RXRalpha). Our findings
      provide a new mechanistic explanation for the neuroprotective role of RA in AD
      pathology and add to the previous data showing the importance of RA signaling as
      a target for AD therapy. 

PMID- 23530931
TI  - Correlating structure with thermal properties for a series of 1-alkyl-4-methyl
      1,2,4-triazolium ionic liquids.
AB  - Thermal properties (T(m) and T(d)) are reported for a series of 1-alkyl-4-methyl
      1,2,4-triazolium ionic liquids where the alkyl chain length R and anion [X(-)]
      were varied. The highest melting transitions were observed when a longer alkyl
      chain or smaller anion was employed. Thermal stability was the greatest when
      anions with weak hydrogen bonding capability were used. Correlations were also
      made between (1)H NMR chemical shift values in acetone-d6 and the hydrogen
      bonding capability of the anion.

PMID- 23530930
TI  - Salvage therapy using FLT3 inhibitors may improve long-term outcome of relapsed
      or refractory AML in patients with FLT3-ITD.
AB  - To determine the long-term efficacy of FLT3 inhibitors (FLT3i) in the salvage
      setting for relapsed and refractory (rel/ref) acute myeloid leukemia (AML) with
      FLT3 internal tandem duplication (AML FLT3-ITD), we conducted a retrospective
      study of 120 patients with rel/ref AML FLT3-ITD who received salvage therapy with
      either FLT3i-containing regimen (FLT3i group, N = 45) or conventional cytotoxic
      regimen (conventional group, N = 75). The median overall survival (OS) after the
      first salvage in the FLT3i group was 6.9 vs. 4.6 months in the conventional group
      (P = 0.17). The OS was better in the FLT3i group among patients with initial
      complete remission (CR) duration <=12 months or with primary refractory disease
      (6.9 vs. 3.7 months; P < 0.01). The OS was better when FLT3i was combined with
      cytotoxic agents versus monotherapy (17 vs. 4.8 months; P = 0.017). Multivariate
      analysis revealed that the use of FLT3i was an independent predictor of OS
      (hazard ratio 0.58; 95% confidence interval, 0.38-0.88). Incorporating FLT3i into
      salvage strategies may improve long-term outcome of patients with AML FLT3-ITD.
      Prospective studies to validate this conclusion are warranted.

PMID- 23530932
TI  - Depolarization alters phenotype, maintains plasticity of pre-differentiated
      mesenchymal stem cells.
AB  - Although adult stem cell transplantation has been implemented as a therapy for
      tissue repair, it is limited by the availability of functional adult stem cells.
      A potential approach to generate stem and progenitor cells may be to modulate the
      differentiated status of somatic cells. Therefore, there is a need for a better
      understanding of how the differentiated phenotype of mature cells is regulated.
      We hypothesize that bioelectric signaling plays an important role in the
      maintenance of the differentiated state, as it is a functional regulator of the
      differentiation process in various cells and tissues. In this study, we asked
      whether the mature phenotype of osteoblasts and adipocytes derived from human
      mesenchymal stem cells (hMSCs) could be altered by modulation of their membrane
      potential. hMSC-derived osteoblasts and adipocytes were depolarized by treatment
      with ouabain, a Na+/K+ ATPase inhibitor, or by treatment with high concentrations
      of extracellular K+. To characterize the effect of voltage modulation on the
      differentiated state, the depolarized cells were evaluated for (1) the loss of
      differentiation markers; (2) the upregulation of stemness markers and stem
      properties; and (3) differences in gene expression profiles in response to
      voltage modulation. hMSC-derived osteoblasts and adipocytes exhibited significant
      downregulation of bone and fat tissue markers in response to depolarization,
      despite the presence of differentiation-inducing soluble factors, suggesting that
      bioelectric signaling overrides biochemical signaling in the maintenance of cell
      state. Suppression of the osteoblast or adipocyte phenotype was not accompanied
      by upregulation of genes associated with the stem state. Thus, depolarization
      does not activate the stem cell genetic signature and therefore does not induce a
      full reprogramming event. However, after transdifferentiating the depolarized
      cells to evaluate for multi-lineage potential, depolarized osteoblasts
      demonstrated improved ability to achieve correct adipocyte morphology compared to
      non-depolarized osteoblasts. The present study thus demonstrates that
      depolarization reduces the differentiated phenotype of hMSC-derived cells and
      improves their transdifferentiation capacity, but does not restore a stem-like
      genetic profile. Through global transcript profiling of depolarized osteoblasts,
      we identified pathways that may mediate the effects of voltage signaling on cell
      state, which will require detailed mechanistic inquiry in future studies.

PMID- 23530933
TI  - Giant cell tumor of bone in a child with Goltz syndrome.
AB  - Giant cell tumor of bone is a neoplasm that is rarely seen in children. Goltz
      syndrome is a disorder that affects multiple ectodermal and mesodermal tissues
      and has occasionally been associated with giant cell tumors of bone. Our case of
      giant cell tumor in a 5-year-old girl with Goltz syndrome suggests that this
      syndrome provides a unique situation wherein the practitioner should consider
      giant cell tumor of bone, even in a pediatric setting.

PMID- 23530934
TI  - The role of flagella and chemotaxis genes in host pathogen interaction of the
      host adapted Salmonella enterica serovar Dublin compared to the broad host range
      serovar S. Typhimurium.
AB  - BACKGROUND: The importance of flagella and chemotaxis genes in host pathogen
      interaction in Salmonella enterica is mainly based on studies of the broad host
      range serovar, S. Typhimurium, while little is known on the importance in host
      specific and host adapted serovars, such as S. Dublin. In the current study we
      have used previously characterized insertion mutants in flagella and chemotaxis
      genes to investigate this and possible differences in the importance between the
      two serovars. RESULTS: fliC (encoding the structural protein of the flagella) was
      essential for adhesion and fliC and cheB (CheB restores the chemotaxis system to
      pre-stimulus conformation) were essential for invasion of S. Dublin into
      epithelial Int407 cells. In S. Typhimurium, both lack of flagella (fliC/fljB
      double mutant) and cheB influenced adhesion, and invasion was influenced by lack
      of both cheA (the histidine-kinase of the chemotaxis system), fliC/fljB and cheB
      mutation. Uptake in J774A.1 macrophage cells was significantly reduced in cheA,
      cheB and fliC mutants of S. Dublin, while cheA was dispensable in S. Typhimurium.
      Removal of flagella in both serotypes caused an increased ability to propagate
      intracellular in J774 macrophage cells and decreased cytotoxicity toward these
      cells. Flagella and chemotaxis genes were found not to influence the oxidative
      response. The induction of IL-6 from J774A-1 cells depended on the presence of
      flagella in S. Typhimurium, whilst this was not the case following challenge with
      S. Dublin. Addition of fliC from S. Typhimurium in trans to a fliC mutant of S.
      Dublin increased cytotoxicity but it did not increase the IL-6 production.
      Flagella were demonstrated to contribute to the outcome of infection following
      oral challenge of mice in S. Dublin, while an S. Typhimurium fliC/fljB mutant
      showed increased virulence following intra peritoneal challenge. CONCLUSIONS: The
      results showed that flagella and chemotaxis genes differed in their role in host
      pathogen interaction between S. Dublin and S. Typhimurium. Notably, lack of
      flagella conferred a more virulent phenotype in S. Typhimurium at systemic sites,
      while this was not the case in S. Dublin. In vitro assays suggested that this
      could be related to flagella-induced induction of the IL-6 pro-inflammatory
      response, but further in vivo studies are needed to confirm this.

PMID- 23530935
TI  - Intramuscular glargine with or without concurrent subcutaneous administration for
      treatment of feline diabetic ketoacidosis.
AB  - OBJECTIVE: To describe treatment response and outcome in 15 cats with diabetic
      ketoacidosis (DKA) initially stabilized with glargine administered
      intramuscularly (IM) with or without subcutaneous (SC) glargine. MATERIALS AND
      METHODS: Fifteen cats diagnosed with DKA were initially administered IM glargine
      (1-2 U) and in most cats (12/15 cats) this was combined with SC glargine (1-3 U).
      This was followed by intermittent IM glargine as required at intervals of 2 or
      more hours (range 2-22 h) and SC glargine (1-2 U) every 12 hours. KEY FINDINGS:
      All 15 cats survived and were discharged from hospital (median 4 d; range 2-5 d)
      and one-third (5/15) of cats subsequently achieved remission (median time 20 d;
      range 15-29 d). Complications included hypokalemia and hypophosphatemia, which
      were likely the result of DKA therapy rather than glargine treatment
      specifically. SIGNIFICANCE: This study demonstrates that glargine administered IM
      is an effective treatment for DKA in cats, and may provide an alternative to
      regular insulin. The same vial used for initial treatment of DKA can then be used
      for subsequent management with SC glargine injections. Future prospective
      randomized controlled trials evaluating clinical outcomes in cats with DKA using
      different types and routes of administration of insulin are warranted. A
      prospective randomized controlled trial is required to compare outcomes for IM
      and IV administration of glargine and regular insulin in DKA cats with or without
      SC glargine.

PMID- 23530936
TI  - Selenium: a brief review and a case report of selenium responsive cardiomyopathy.
AB  - BACKGROUND: The authors review the role of selenium and highlight possible low
      selenium levels in soil that may result in deficient states in Saudi Arabia. CASE
      PRESENTATION: The authors report a case of selenium-responsive cardiomyopathy in
      a 15-month old Saudi Arabian boy. This case of selenium deficiency causing
      dilated cardiomyopathy is presented with failure to thrive, prolonged fever and
      respiratory distress. The investigations revealed selenium deficiency. Selenium
      supplementation along with anti-failure therapy [Furosimide, Captopril] was
      administered for 6 months. Following therapy the cardiac function, hair, skin and
      the general health of the patient improved significantly. CONCLUSION: The patient
      with dilated cardiomyopathy of unknown etiology, not responding to usual
      medication may be deficient in selenium. Serum selenium measurements should be
      included in the diagnostic work-up to ensure early detection and treatment of the
      disease. The selenium level in the Saudi population needs be determined.
      Vulnerable populations have to undergo regular selenium measurements and
      supplementation if indicated. Dependence on processed foods suggests that the
      Saudi population fortify themselves with nutrient and micronutrient supplements
      in accordance to the RDA.

PMID- 23530937
TI  - Perioperative blood pressure variability in the treated hypertensive patients.
AB  - Perioperative blood pressure (BP) management is important to prevent
      cardiovascular complication, especially for hypertensive patients. In the present
      study, we investigated perioperative BP variability and contributing factors in
      hypertensive patients. Subjects were 28 treated hypertensive patients who
      underwent total or subtotal gastrectomy. Ambulatory BP monitoring was carried out
      before and after (16 days in average) the surgery. Angiotensin converting enzyme
      (ACE) inhibitors, angiotensin receptor blockers (ARBs), and diuretics were
      withdrawn on the previous day, while other drugs were administered until the day
      of surgery. BP, body weight, blood chemistry, as well as the use of intravenous
      vasopressor or vasodepressor agents during the perioperative period were
      investigated. The 24-hour BP before surgery was 124 +/- 19/70 +/- 12 mm Hg, and
      the number of antihypertensive drugs was 1.8. In 22 patients, intravenous
      vasopressor agents were used during surgery, while another patient received
      intravenous vasodepressor agents after surgery. The 24-hour BP significantly
      decreased after surgery (-8.2 +/- 14.7/-2.6 +/- 7.3 mm Hg). Body weight, serum
      Na, and hematocrit also decreased. There were nine patients whose 24-hour
      systolic BP decreased by more than 10 mm Hg and for two patients more than 20 mm
      Hg. The decrease in BP correlated with the change in serum Na. Forty-three
      percent of the patients who took ACE inhibitors/ARBs showed BP reduction greater
      than 10 mm Hg, while 25% of the patients without these drugs showed such BP
      reduction. Our findings suggest that 24-hour BP decreases after gastrectomy.
      Patients taking ACE inhibitors or ARBs may need careful monitoring to prevent
      excessive BP fall.

PMID- 23530938
TI  - Equivalency of Galapagos giant tortoises used as ecological replacement species
      to restore ecosystem functions.
AB  - Loss of key plant-animal interactions (e.g., disturbance, seed dispersal, and
      herbivory) due to extinctions of large herbivores has diminished ecosystem
      functioning nearly worldwide. Mitigating for the ecological consequences of large
      herbivore losses through the use of ecological replacements to fill extinct
      species' niches and thereby replicate missing ecological functions has been
      proposed. It is unknown how different morphologically and ecologically a
      replacement can be from the extinct species and still provide similar functions.
      We studied niche equivalency between 2 phenotypes of Galapagos giant tortoises
      (domed and saddlebacked) that were translocated to Pinta Island in the Galapagos
      Archipelago as ecological replacements for the extinct saddlebacked giant
      tortoise (Chelonoidis abingdonii). Thirty-nine adult, nonreproductive tortoises
      were introduced to Pinta Island in May 2010, and we observed tortoise resource
      use in relation to phenotype during the first year following release. Domed
      tortoises settled in higher, moister elevations than saddlebacked tortoises,
      which favored lower elevation arid zones. The areas where the tortoises settled
      are consistent with the ecological conditions each phenotype occupies in its
      native range. Saddlebacked tortoises selected areas with high densities of the
      arboreal prickly pear cactus (Opuntia galapageia) and mostly foraged on the
      cactus, which likely relied on the extinct saddlebacked Pinta tortoise for seed
      dispersal. In contrast, domed tortoises did not select areas with cactus and
      therefore would not provide the same seed-dispersal functions for the cactus as
      the introduced or the original, now extinct, saddlebacked tortoises.
      Interchangeability of extant megaherbivores as replacements for extinct forms
      therefore should be scrutinized given the lack of equivalency we observed in
      closely related forms of giant tortoises. Our results also demonstrate the value
      of trial introductions of sterilized individuals to test niche equivalency among
      candidate analog species.

PMID- 23530939
TI  - Mifepristone improves chemo-radiation response in glioblastoma xenografts.
AB  - BACKGROUND: We have investigated the ability of Mifepristone, an anti-progestin
      and anti-glucocorticoid drug, to modulate the antitumor effect of current
      standard clinical treatment in glioblastoma xenografts. METHODS: The effect of
      radiation alone or combined with Mifepristone and Temozolamide was evaluated on
      tumor growth in glioblastoma xenografts, both in terms of preferentially
      triggering tumor cell death and inhibiting angiogenesis. Tumor size was measured
      once a week using a caliper and tumor metabolic-activity was carried out by
      molecular imaging using a microPET/CT scanner. The effect of Mifepristone on the
      expression of angiogenic factors after concomitant radio-chemotherapy was
      determined using a quantitative real-time PCR analysis of VEGF gene expression.
      RESULTS: The analysis of the data shows a significant antitumoral effect by the
      simultaneous administration of radiation-Mifepristone-Temozolamide in comparison
      with radiation alone or radiation-Temozolamide. CONCLUSION: Our results suggest
      that Mifepristone could improve the efficacy of chemo-radiotherapy in
      Glioblastoma. The addition of Mifepristone to standard radiation-Temozolamide
      therapy represents a potential approach as a chemo-radio-sensitizer in treating
      GBMs, which have very limited treatment options.

PMID- 23530940
TI  - Development of a detection algorithm for statin-induced myopathy using electronic
      medical records.
AB  - WHAT IS KNOWN AND OBJECTIVE: Demonstration of the utility of electronic medical
      records (EMRs) for pharmacovigilance (PV) has been highly anticipated. Analysis
      using appropriately selected EMRs should enable accurate estimation of adverse
      drug event (ADE) frequencies and thus promote appropriate regulatory actions.
      Statin-induced myopathy (SIM) is a clinically important ADE, but
      pharmacoepidemiological methodology for detecting this ADE with high
      predictability has not yet been established. This study aimed to develop a
      detection algorithm, highly selective for SIM using EMRs. METHODS: We collected
      EMRs on prescriptions, laboratory tests, diagnoses and medical practices from the
      hospital information system of Kobe University Hospital, Japan, for a total of
      5109 patients who received a statin prescription from April 2006 to March 2009.
      The current algorithm for extracting SIM-suspected patients consisted of three
      steps: (i) event detection: increase in creatine kinase (CK) and subsequent
      statin discontinuation, (ii) filtration by exclusion factors (disease
      diagnosis/medical practices) and (iii) refinement by the time course of CK values
      (baseline, event and recovery). A causal relationship between the event and
      statin prescription (probable/possible/unlikely) was judged by review of patient
      medical charts by experienced pharmacists. The utility of the current algorithm
      was assessed by calculating the positive predictive value (PPV). In a comparative
      analysis, subjects screened in step 1 were extracted by the diagnostic term/code
      for 'myopathy/rhabdomyolysis', and the PPV of this diagnostic data approach was
      also estimated. RESULTS AND DISCUSSION: Five subjects with suspected SIM were
      identified using our proposed algorithm, giving a frequency of 0.1% for the
      adverse event. Review of the medical charts revealed that the causal association
      of SIM with statin use was judged as 'Likely (probable/possible)' for all five
      suspected patients; thus, the PPV was estimated as 100% (95% confidence interval:
      56.6-100%). The higher utility of the current algorithm compared with the
      diagnostic data approach was also shown by assessing the PPV (100 vs. 33.3%).
      WHAT IS NEW AND CONCLUSION: We report on a detection algorithm with high
      predictability for SIM using EMRs. Combined use of exclusion criteria for
      disease, medical practice data and time course of CK values contributes to better
      prediction of SIM. The utility of the proposed algorithm should be further
      confirmed in a larger study.

PMID- 23530941
TI  - Enhanced surveillance of invasive listeriosis in the Lombardy region, Italy, in
      the years 2006-2010 reveals major clones and an increase in serotype 1/2a.
AB  - BACKGROUND: Invasive listeriosis is a rare, life-threatening foodborne disease.
      Lombardy, an Italian region accounting for 16% of the total population, reported
      55% of all listeriosis cases in the years 2006-2010. The aim of our study was to
      provide a snapshot of listeriosis epidemiology in this region after the
      implementation of a voluntary laboratory-based surveillance system. METHODS: We
      characterized by serotyping, pulsed-field gel electrophoresis, multilocus
      sequence typing and detection of epidemic clone markers, 134 isolates from 132
      listeriosis cases, including 15 pregnancy-related cases, occurring in the years
      2006-2010 in Lombardy. Demographic and clinical characteristics of cases have
      also been described. RESULTS: The mean age of non pregnancy-associated cases was
      64.7 years, with 55.9% of cases being older than 65 years. Cases having no
      underlying medical conditions accounted for 11.6%. The all-cause fatality rate of
      83 cases with a known survival outcome was 25.3%.Serotypes 1/2a and 4b comprised
      52.2% and 38.8% of isolates, respectively. Seventy-three AscI pulsotypes and 25
      sequence types assigned to 23 clonal complexes were recognized. Moreover, 53
      (39.5%) isolates tested positive for the epidemic clone markers. Twelve molecular
      subtype clusters including at least three isolates were detected, with cluster 11
      (1/2a/ST38) including 31 isolates identified during the entire study period. No
      outbreaks were notified to public health authorities during this period.
      CONCLUSIONS: The findings of our study proved that epidemiology of listeriosis in
      Lombardy is characterized by a high prevalence of major clones and the increasing
      role of serotype 1/2a. Molecular subtyping is an essential tool in the
      epidemiology and surveillance of listeriosis. Rapid molecular cluster detection
      could alert about putative outbreaks, thus increasing the chance of detecting and
      inactivating routes of transmission.

PMID- 23530942
TI  - Overall evaluation of combustion and NO(x) emissions for a down-fired 600 MW(e)
      supercritical boiler with multiple injection and multiple staging.
AB  - To achieve significant reductions in NOx emissions and to eliminate strongly
      asymmetric combustion found in down-fired boilers, a deep-air-staging combustion
      technology was trialed in a down-fired 600 MWe supercritical utility boiler. By
      performing industrial-sized measurements taken of gas temperatures and species
      concentrations in the near wing-wall region, carbon in fly ash and NOx emissions
      at various settings, effects of overfire air (OFA) and staged-air damper openings
      on combustion characteristics, and NOx emissions within the furnace were
      experimentally determined. With increasing the OFA damper opening, both
      fluctuations in NOx emissions and carbon in fly ash were initially slightly over
      OFA damper openings of 0-40% but then lengthened dramatically in openings of 40
      70% (i.e., NOx emissions reduced sharply accompanied by an apparent increase in
      carbon in fly ash). Decreasing the staged-air declination angle clearly increased
      the combustible loss but slightly influenced NOx emissions. In comparison with
      OFA, the staged-air influence on combustion and NOx emissions was clearly weaker.
      Only at a high OFA damper opening of 50%, the staged-air effect was relatively
      clear, i.e., enlarging the staged-air damper opening decreased carbon in fly ash
      and slightly raised NOx emissions. By sharply opening the OFA damper to deepen
      the air-staging conditions, although NOx emissions could finally reduce to 503
      mg/m(3) at 6% O2 (i.e., an ultralow NOx level for down-fired furnaces), carbon in
      fly ash jumped sharply to 15.10%. For economical and environment-friendly boiler
      operations, an optimal damper opening combination (i.e., 60%, 50%, and 50% for
      secondary air, staged-air, and OFA damper openings, respectively) was recommended
      for the furnace, at which carbon in fly ash and NOx emissions attained levels of
      about 10% and 850 mg/m(3) at 6% O2, respectively.

PMID- 23530943
TI  - News from Clinical Research Office of the Endourological Society (Croes).

PMID- 23530944
TI  - Abstracts of the Fourth Biennial Congress of the Asian-Pacific Hepato-Pancreato
      Biliary Association. March 27-30, 2013. Shanghai, China.

PMID- 23530945
TI  - Validation of an ELISA for urinary dopamine: applications in monitoring treatment
      of dopamine-related disorders.
AB  - Dopamine is a catecholamine that serves as a neurotransmitter in the central and
      peripheral nervous system. Non-invasive, reliable, and high-throughput techniques
      for its quantification are needed to assess dysfunctions of the dopaminergic
      system and monitor therapies. We developed and validated a competitive ELISA for
      direct determination of dopamine in urine samples. The method provides high
      specificity, good accuracy, and precision (average inter-assay variation < 12%).
      The analysis is not affected by general urinary components and structurally
      related drugs and metabolites. The correlation between ELISA and LC-MS/MS
      analyses was very good (r = 0.986, n = 28). The reference range was 64-261 MUg/g
      Cr (n = 64). Week-to-week biological variations of second morning urinary
      dopamine under free-living conditions were 23.9% for within- and 35.5% for
      between-subject variation (n = 10). The assay is applied in monitoring
      Parkinson's disease patients under different treatments. Urinary dopamine levels
      significantly increase in a dose-dependent manner for Parkinson's disease
      patients under l-DOPA treatment. The present ELISA provides a cost-effective
      alternative to chromatographic methods to monitor patients receiving dopamine
      restoring treatment to ensure appropriate dosing and clinical efficacy. The
      method can be used in pathological research for the assessment of possible
      peripheral biological markers for disorders related to the dopaminergic system.

PMID- 23530946
TI  - Effects of dorzolamide-timolol and brimonidine-timolol on retinal vascular
      autoregulation and ocular perfusion pressure in primary open angle glaucoma.
AB  - PURPOSE: To assess whether dorzolamide 2%-timolol 0.5% (D/T) and/or brimonidine
      0.2%-timolol 0.5% (B/T) alters retinal vascular autoregulation (RVA) and seated
      ocular perfusion pressure (sOPP) in primary open angle glaucoma (POAG) patients
      who demonstrate retinal vascular dysregulation (RVD) on timolol 0.5% alone.
      METHODS: In this prospective, observer-masked, crossover study, 21 POAG patients
      with untreated intraocular pressure (IOP) >21 mmHg were treated for 6 weeks with
      timolol 0.5%. Subsequently, we measured inferior temporal retinal artery blood
      flow in the left eye with subjects seated and then while reclined for 30 min
      using the Canon Laser Blood Flowmeter. Subjects with a change in retinal blood
      flow in response to posture change outside of the range previously found in
      healthy subjects were designated as having RVD and randomized to either D/T or
      B/T for 6 weeks and re-tested. This was followed by treatment with the opposite
      medication. RESULTS: Seven of the 21 subjects demonstrated RVD in response to
      posture change following timolol 0.5%. Multiple linear regression analysis
      indicated that lower sOPP was the main determinant of RVD (P=0.033). After
      treatment with D/T, all 7 converted from RVD to normal RVA status (P=0.001). Four
      of 6 subjects showed a similar return to normal RVA following B/T (P=0.066). Mid
      morning sOPP was 41.1+/-5.5 mmHg post-timolol, 46.3+/-6.5 mmHg post-D/T, and
      38.6+/-6.0 mmHg post-B/T (D/T vs. B/T, P=0.026). CONCLUSIONS: D/T significantly
      improved RVA in POAG patients exhibiting RVD while on timolol 0.5% alone. D/T
      also increased sOPP compared to B/T. There was no significant difference (P=0.37)
      between D/T and B/T in improving RVA.

PMID- 23530947
TI  - Probing with mitomycin-C in adults with nasolacrimal duct obstruction.

PMID- 23530948
TI  - Changes in trabecular bone microarchitecture in postmenopausal women with and
      without type 2 diabetes: a two year longitudinal study.
AB  - BACKGROUND: The risk of experiencing an osteoporotic fracture is greater for
      adults with type 2 diabetes despite higher than normal bone mineral density
      (BMD). In addition to BMD, trabecular bone microarchitecture contributes to bone
      strength, but is not assessed using conventional BMD measurement by dual x-ray
      absorptiometry (DXA). The aim of this study was to compare two year changes in
      trabecular bone microarchitecture in women with and without type 2 diabetes.
      METHODS: We used a 1 Tesla magnetic resonance imaging (MRI) scanner to acquire
      axial images (resolution 195 MUm * 195 MUm * 1000 MUm) of the distal radius. We
      report the change in the number and size of trabecular bone holes, bone volume
      fraction (BVTV), trabecular thickness (Tb.Th), number (Tb.N) and separation
      (Tb.Sp), endosteal area, nodal and branch density for each group. Lumbar spine
      and proximal femur BMD were measured with DXA (Hologic, Discovery QDR4500A) at
      baseline and follow-up. Using a multivariable linear regression model, we
      evaluated whether the percent change in the trabecular bone microarchitecture
      variables differed between women with and without type 2 diabetes. RESULTS: Of
      the 54 participants at baseline with valid MRI image sets, 37 participants
      (baseline mean [SD] age, 70.8 [4.4] years) returned for follow-up assessment
      after 25.4 [1.9] months. Lumbar spine BMD was greater for women with diabetes
      compared to without diabetes at both baseline and follow-up. After adjustment for
      ethnicity, women with diabetes had a higher percent increase in number of
      trabecular bone holes compared to controls (10[1] % versus -7 [2]%, p=0.010),
      however results were no longer significant after adjustment for multiple
      comparisons (p=0.090). There were no differences in the change in other
      trabecular bone microarchitecture variables between groups. CONCLUSION: There
      were no differences in percent change in trabecular bone microarchitecture
      variables over two years in women with type 2 diabetes compared to women without
      diabetes. This study provides feasibility data, which will inform future trials
      assessing change in trabecular bone microarchitecture in women with type 2
      diabetes. Larger studies using higher resolution imaging modalities that can
      assess change in trabecular and cortical bone compartments in women with type 2
      diabetes are needed.

PMID- 23530949
TI  - Overcoming resistance to beta-lactam antibiotics.
AB  - beta-Lactam antibiotics are one of the most important antibiotic classes but are
      plagued by problems of resistance, and the development of new beta-lactam
      antibiotics through side-chain modification of existing beta-lactam classes is
      not keeping pace with resistance development. In this JOCSynopsis, we summarize
      small molecule strategies to overcome resistance to beta-lactam antibiotics.
      These approaches include the development of beta-lactamase inhibitors and
      compounds that interfere with the ability of the bacteria to sense an antibiotic
      threat and activate their resistance mechanisms.

PMID- 23530950
TI  - Ticlopidine-associated ADAMTS13 activity deficient thrombotic thrombocytopenic
      purpura in 22 persons in Japan: a report from the Southern Network on Adverse
      Reactions (SONAR).

PMID- 23530951
TI  - Imaging mass spectrometry in neuroscience.
AB  - Imaging mass spectrometry is an emerging technique of great potential for
      investigating the chemical architecture in biological matrices. Although the
      potential for studying neurobiological systems is evident, the relevance of the
      technique for application in neuroscience is still in its infancy. In the present
      Review, a principal overview of the different approaches, including matrix
      assisted laser desorption ionization and secondary ion mass spectrometry, is
      provided with particular focus on their strengths and limitations for studying
      different neurochemical species in situ and in vitro. The potential of the
      various approaches is discussed based on both fundamental and biomedical
      neuroscience research. This Review aims to serve as a general guide to
      familiarize the neuroscience community and other biomedical researchers with the
      technique, highlighting its great potential and suitability for comprehensive and
      specific chemical imaging. 

PMID- 23530956
TI  - Development of a proactive care program (U-CARE) to preserve physical functioning
      of frail older people in primary care.
AB  - PURPOSE: Care for older patients in primary care is currently reactive,
      fragmented, and time consuming. An innovative structured and proactive primary
      care program (U-CARE) has been developed to preserve physical functioning and
      enhance quality of life of frail older people. This study describes in detail the
      development process of the U-CARE program to allow its replication. METHODS: The
      framework of the Medical Research Council (MRC) for the development and
      evaluation of complex interventions was used as a theoretical guide for the
      design of the U-CARE program. An extended stepwise multimethod procedure was used
      to develop U-CARE. A team of researchers, general practitioners, registered
      practice nurses, experts, and an independent panel of older persons was involved
      in the development process to increase its feasibility in clinical practice. A
      systematic review of the literature and of relevant guidelines, combined with
      clinical practice experience and expert opinion, was used for the development of
      the intervention. FINDINGS: Based on predefined potentially effective guiding
      components, the U-CARE program comprises three steps: a frailty assessment, a
      comprehensive geriatric assessment at home followed by a tailor-made care plan,
      and multiple follow-up visits. Evidence-based care plans were developed for 11
      geriatric conditions. The feasibility in clinical practice was tested and
      approved by experienced registered practice nurses. CONCLUSIONS: Using the MRC
      Framework, a detailed description of the development process of the innovative U
      CARE program is provided, which is often missing in reports of complex
      intervention trials. Based on our feasibility-pilot study, the general
      practitioners and the registered practice nurses indicated that the U-CARE
      intervention is feasible in clinical practice. CLINICAL RELEVANCES: The U-CARE
      program consists of promising components and has the potential to improve the
      care of older patients.

PMID- 23530957
TI  - Pediatric non alcoholic fatty liver disease: old and new concepts on development,
      progression, metabolic insight and potential treatment targets.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver
      disease in children. NAFLD has emerged to be extremely prevalent, and predicted
      by obesity and male gender. It is defined by hepatic fat infiltration >5%
      hepatocytes, in the absence of other causes of liver pathology. It includes a
      spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to
      various degrees of necrotic inflammation and fibrosis (non-alcoholic
      steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with
      severe metabolic impairments, determining an increased risk of developing the
      metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with
      the consequent need for liver transplantation. Both genetic and environmental
      factors seem to be involved in the development and progression of the disease,
      but its physiopathology is not yet entirely clear. In view of this mounting
      epidemic phenomenon involving the youth, the study of NAFLD should be a priority
      for all health care systems. This review provides an overview of current and new
      clinical-histological concepts of pediatric NAFLD, going through possible
      implications into patho-physiolocical and therapeutic perspectives.

PMID- 23530958
TI  - Genotype-phenotype matching analysis of 38 Lactococcus lactis strains using
      random forest methods.
AB  - BACKGROUND: Lactococcus lactis is used in dairy food fermentation and for the
      efficient production of industrially relevant enzymes. The genome content and
      different phenotypes have been determined for multiple L. lactis strains in order
      to understand intra-species genotype and phenotype diversity and annotate gene
      functions. In this study, we identified relations between gene presence and a
      collection of 207 phenotypes across 38 L. lactis strains of dairy and plant
      origin. Gene occurrence and phenotype data were used in an iterative gene
      selection procedure, based on the Random Forest algorithm, to identify genotype
      phenotype relations. RESULTS: A total of 1388 gene-phenotype relations were
      found, of which some confirmed known gene-phenotype relations, such as the
      importance of arabinose utilization genes only for strains of plant origin. We
      also identified a gene cluster related to growth on melibiose, a plant
      disaccharide; this cluster is present only in melibiose-positive strains and can
      be used as a genetic marker in trait improvement. Additionally, several novel
      gene-phenotype relations were uncovered, for instance, genes related to arsenite
      resistance or arginine metabolism. CONCLUSIONS: Our results indicate that
      genotype-phenotype matching by integrating large data sets provides the
      possibility to identify gene-phenotype relations, possibly improve gene function
      annotation and identified relations can be used for screening bacterial culture
      collections for desired phenotypes. In addition to all gene-phenotype relations,
      we also provide coherent phenotype data for 38 Lactococcus strains assessed in
      207 different phenotyping experiments, which to our knowledge is the largest to
      date for the Lactococcus lactis species.

PMID- 23530959
TI  - Multipart copolyelectrolyte adhesive of the sandcastle worm, Phragmatopoma
      californica (Fewkes): catechol oxidase catalyzed curing through peptidyl-DOPA.
AB  - Tube-building sabellariid polychaetes have major impacts on the geology and
      ecology of shorelines worldwide. Sandcastle worms, Phragmatopoma californica
      (Fewkes), live along the western coast of North America. Individual sabellariid
      worms build tubular shells by gluing together mineral particles with a multipart
      polyelectrolytic adhesive. Distinct sets of oppositely charged components are
      packaged and stored in concentrated granules in separate cell types. Homogeneous
      granules contain sulfated macromolecules as counter-polyanion to polycationic Pc2
      and Pc5 proteins, which become major components of the fully cured glue.
      Heterogeneous granules contain polyphosphoproteins, Pc3A/B, paired with divalent
      cations and polycationic Pc1 and Pc4 proteins. Both types of granules contain
      catechol oxidase that catalyzes oxidative cross-linking of L-DOPA. Co-secretion
      of catechol oxidase guarantees rapid and spatially homogeneous curing with
      limited mixing of the preassembled adhesive packets. Catechol oxidase remains
      active long after the glue is fully cured, perhaps providing an active cue for
      conspecific larval settlement.

PMID- 23530960
TI  - Antioxidative burst and hepatoprotective effects of ethanol root extract of
      Hippocratea africana against paracetamol-induced liver injury.
AB  - CONTEXT: Hippocratea africana (Willd.) Loes. ex Engl. (Celastraceae) root is used
      traditionally as an antipoison or antidote to treat liver diseases. OBJECTIVE: To
      evaluate antioxidative burst and hepatoprotective potentials of H. africana
      against paracetamol-induced liver injury in rats. MATERIALS AND METHOD:
      Antioxidative burst activity of the extract (1-100 ug/ml) in whole blood,
      neutrophils and macrophages was investigated using a luminol/lucigenin-based
      chemiluminescence assay. The hepatoprotective effect of the extract (200-600
      mg/kg) was evaluated by the assay of liver function parameters, antioxidant
      enzymes and histopathological studies of the liver. GC-MS analyses of hexane and
      dichloromethane fractions were also carried out. RESULTS AND DISCUSSION: The root
      extract/fractions exerted pronounced inhibition of oxidative burst activity in
      whole blood, neutrophils (intracellular and extracellular) and macrophages (3.04
      99.70%). The administration of the root extract caused significant (p < 0.05
      0.001) reduction of high levels of liver enzymes (AST, ALT and ALP), total
      cholesterol, direct and total bilirubin as well as elevation of serum levels of
      total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology
      of the liver sections of extract and silymarin-treated animals showed reductions
      in the pathological features compared to the paracetamol-treated animals. The
      chemical pathological changes were consistent with histopathological observations
      suggesting a marked hepatoprotective effect of the root extract of H. africana.
      The GC-MS analysis revealed some pharmacologically active compounds. CONCLUSION:
      The results show that the root extract of H. africana has hepatoprotective
      potential probably due to its antioxidative burst activity.

PMID- 23530962
TI  - Anti-infective periodontal therapy promoting improvement in systemic markers of
      HIV infection.
AB  - Research supports the theory that the chronic infectious response occurring in
      periodontal disease may have a role as a risk modifier of systemic diseases. This
      study assessed the impact of HIV-associated chronic periodontitis treatment on
      systemic HIV-related markers (CD4 T lymphocytes cell counts and HIV viral load).
      Fifteen HIV patients presenting chronic periodontitis [at least eight sites
      presenting a probing depth (PD) >4 mm and bleeding] were included in this study.
      Patients received full mouth periodontal treatment with an ultrasonic device and
      supragingival plaque control. Medical (CD4 cell counts and HIV load) as well as
      periodontal clinical parameters [probing pocket depth (PPD), clinical attachment
      level (CAL)] were assessed at baseline and 3 and 6 months after treatment.
      ANOVA/Tukey and Pearson's correlation tests were used for statistical analysis
      (alpha=5%). The results showed that PPD reduction and CAL gain were statistically
      significant at 3 and 6 months after periodontal therapy (p<0.05). At 6 months,
      CAL gain was 0.6+/-0.5 mm and PPD reduction was 0.7+/-0.5 mm. At the same time, a
      statistically significant increase in CD4 cell counts could be seen after the
      third month (p<0.05) and sixth month (p<0.05). Moreover, at 6 months, the
      relationship between the improvement in clinical parameters, i.e., PPD reduction,
      and the number of TCD4 lymphocytes could be highlighted. This was shown as the
      greater the PPD reduction, the greater the increase in TCD4 cells (r=0.68,
      p=0.02). These data suggest that periodontitis treatment could be associated with
      an improvement in medical conditions in HIV subjects.

PMID- 23530963
TI  - Characteristics and essences upon conjugation of imidacloprid with two model
      proteins.
AB  - Since the introduction of imidacloprid in the early 1990s, it has become one of
      the most widely applied insecticides, and currently represents about 20% of the
      global pesticide market (Tomizawa, M.; Casida, J. E. J. Agric. Food Chem 2011,
      59, 2883-2886). In the context of this study, our major aim was to
      comprehensively scrutinize the nature of imidacloprid with two typical model
      proteins, lysozyme and albumin, by means of circular dichroism (CD), steady-state
      and time-resolved fluorescence, and molecular modeling at the molecular level.
      Far-UV CD verified that the spatial structure of both proteins was altered with a
      distinct reduction of alpha helix in the presence of imidacloprid suggesting
      unfolding of the protein (i.e., protein damage). The data of steady-state and
      time-resolved fluorescence showed that the conjugation of imidacloprid with
      lysozyme yielded quenching by a static mechanism (KSV = 3.841 * 10(4) M(-1)),
      while combined static and dynamic properties existed for albumin tryptophan (Trp)
      214 fluorescence. Molecular modeling simulations displayed that the imidacloprid
      binding site was near to the Trp-62 and Trp-63 residues of lysozyme, and it was
      located at the subdomain IIA (warfarin-azapropazone site) of albumin.
      Furthermore, the primary forces between protein and imidacloprid are hydrogen
      bond, hydrophobic, and pi-pi interactions, but the affinity of lysozyme with
      imidacloprid is much lower than albumin, probably because the affinity
      distinctions stem from discrepancy in the three-dimensional structure of the two
      globular proteins. The results presented here will help to further understand the
      credible mechanism by which the toxicological implication of neonicotinoid
      insecticides is palliated by carrier protein.

PMID- 23530964
TI  - The relationship between morning hypertension and sleep quality in patients with
      obstructive sleep apnea syndrome.
AB  - This study aimed to investigate the prevalence of abnormal diurnal blood pressure
      (BP) profiles in patients with obstructive sleep apnea syndrome (OSAS) in
      relation to the data of a sleep study. Total 103 patients newly diagnosed with
      OSAS underwent overnight polysomnography and 24-hour ambulatory BP measurements.
      Patients without morning or nocturnal hypertension (control group), patients with
      morning hypertension but not nocturnal hypertension (surge-type group), and
      patients with both morning and nocturnal hypertension (sustained-type group) were
      compared. Morning hypertension was present in 54 patients (16 surge-type and 38
      sustained-type). The apnea-hypopnea index and sleep efficiency were higher and
      lower, respectively, in the sustained-type group than in the other groups. Slow
      wave sleep incidence was significantly lower in the sustained-type and surge-type
      groups than in the control group. These results suggest that approximately half
      the OSAS patients displayed morning hypertension, the sustained-type being more
      common than the surge-type. Poor sleep quality plays an important role in the
      pathogenesis of morning hypertension in both the sustained- and the surge-type
      group.

PMID- 23530965
TI  - Evaluation of PCR procedures for detecting and quantifying Leishmania donovani
      DNA in large numbers of dried human blood samples from a visceral leishmaniasis
      focus in Northern Ethiopia.
AB  - BACKGROUND: Visceral Leishmaniasis (VL) is a disseminated protozoan infection
      caused by Leishmania donovani parasites which affects almost half a million
      persons annually. Most of these are from the Indian sub-continent, East Africa
      and Brazil. Our study was designed to elucidate the role of symptomatic and
      asymptomatic Leishmania donovani infected persons in the epidemiology of VL in
      Northern Ethiopia. METHODS: The efficacy of quantitative real-time kinetoplast
      DNA/PCR (qRT-kDNA PCR) for detecting Leishmania donovani in dried-blood samples
      was assessed in volunteers living in an endemic focus. RESULTS: Of 4,757 samples,
      680 (14.3%) were found positive for Leishmania k-DNA but most of those (69%) had
      less than 10 parasites/ml of blood. Samples were re-tested using identical
      protocols and only 59.3% of the samples with 10 parasite/ml or less were qRT-kDNA
      PCR positive the second time. Furthermore, 10.8% of the PCR negative samples were
      positive in the second test. Most samples with higher parasitemias remained
      positive upon re-examination (55/59 =93%). We also compared three different
      methods for DNA preparation. Phenol-chloroform was more efficient than sodium
      hydroxide or potassium acetate. DNA sequencing of ITS1 PCR products showed that
      20/22 samples were Leishmania donovani while two had ITS1 sequences homologous to
      Leishmania major. CONCLUSIONS: Although qRT-kDNA PCR is a highly sensitive test,
      the dependability of low positives remains questionable. It is crucial to
      correlate between PCR parasitemia and infectivity to sand flies. While optimal
      sensitivity is achieved by targeting k-DNA, it is important to validate the
      causative species of VL by DNA sequencing.

PMID- 23530966
TI  - Partial liver volume radioembolization induces hypertrophy in the spared
      hemiliver and no major signs of portal hypertension.
AB  - BACKGROUND: Post-treatment contralateral hemiliver hypertrophy has created an
      interest in lobar liver radioembolization (RE) as a pre-surgery tool. METHODS:
      Liver and spleen volumes and function were studied in 83 patients submitted to
      partial liver volume RE at 4-8 weeks (T1), 10-26 weeks (T2), and >26 weeks (T3)
      after RE. RESULTS: More than half of the patients had cirrhosis with
      hepatocellular carcinoma. The main finding was a progressive increase in the
      volume of the spared hemiliver (mean absolute increase at T3: 230 ml). The
      percentage of patients in whom the baseline ratio of spared volume to total liver
      volume was <40% dropped from 56.6% at baseline to 29.4% at T2 (P < 0.001). A
      significant and progressive increase in spleen volume but not in portal vein
      diameter was also observed. A small percentage of patients developed
      hypersplenism, mostly those without cirrhosis (16.0% at T2). Six patients (five
      with portal vein thrombosis, cirrhosis or both) developed signs of portal
      hypertension by T2. CONCLUSIONS: The present results warrant further studies to
      better elucidate the mechanism underlying this phenomenon of spared hemiliver
      hypertrophy and to investigate its role as an alternative to portal vein
      embolization in the management of patients with potentially resectable liver
      tumours.

PMID- 23530967
TI  - Primary Hodgkin lymphoma of the central nervous system: two case reports and
      review of the literature.
AB  - CNS involvement by systemic Hodgkin lymphoma (HL) is quite rare, but the disease
      limited to the CNS is an exceptionally rare entity. The incidence of CNS-HL has
      been estimated at 0.2-0.5% of cases, but a more recent study has modified that
      figure to less than 0.02%. Like the conventional form, the diagnosis of primary
      CNS-HL rests upon distinct morphological and immunohistochemical characteristics,
      including diagnostic Reed-Sternberg cells, in addition to staging studies
      demonstrating a lack of disease elsewhere. The paucity of cases in the literature
      precludes reliable clinical and demographic data, as well as a consensus on
      treatment and prognosis. We present two cases of primary cerebellar HL, one with
      10-year follow-up, and a relevant review of the literature. 

PMID- 23530968
TI  - Hypokalaemic paralysis in an adult case of Plasmodium vivax malaria.
AB  - Hypokalaemia and its subsequent complications are more often seen in children
      rather than in adults and are more common with falciparum malaria. This is a case
      of a 26-year-old male with Plasmodium vivax malaria who had developed paraparesis
      secondary to hypokalaemia. His treatment involved correction of the potassium
      level as well as the treatment of malaria. Such an atypical manifestation of
      malaria in an adult has not been previously documented.

PMID- 23530970
TI  - Rac1 cycling fast in melanoma with P29S.

PMID- 23530969
TI  - A randomized phase I/II trial of HQK-1001, an oral fetal globin gene inducer, in
      beta-thalassaemia intermedia and HbE/beta-thalassaemia.
AB  - beta-thalassaemia intermedia (BTI) syndromes cause haemolytic anaemia,
      ineffective erythropoiesis, and widespread complications. Higher fetal globin
      expression within genotypes reduces globin imbalance and ameliorates anaemia.
      Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty
      acid derivative, induces gamma-globin expression experimentally and is well
      tolerated in normal subjects. Accordingly, a randomized, blinded, placebo
      controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with
      HbE/beta(0) thalassaemia and seven with beta(+)/beta(0) thalassaemia intermedia,
      to determine effective doses for fetal globin induction, safety, and
      tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at
      four dose levels (10, 20, 30, or 40 mg/kg per day), and subjects were monitored
      for laboratory and clinical events. Pharmacokinetic profiles demonstrated a
      t(1/2) of 10-12 h. Adverse events with HQK-1001 treatment were not significantly
      different from placebo treatment. The 20 mg/kg treatment doses increased median
      HbF above baseline levels by 6.6% and 4.4 g/l (P < 0.01) in 8/9 subjects; total
      haemoglobin (Hb) increased by a mean of 11 g/l in 4/9 subjects. These findings
      identified a safe oral therapeutic which induces fetal globin in BTI. Further
      investigation of HQK-1001 with longer dosing to definitively evaluate its
      haematological potential appears warranted.

PMID- 23530971
TI  - The meaning of evidence-based management to Brazilian senior nurse leaders.
AB  - PURPOSE: The study objective was to understand the meaning of evidence-based
      management for senior nurse leaders in accredited, public hospitals in the State
      of Sao Paulo, Brazil. DESIGN AND METHOD: A phenomenological approach was used to
      analyze interviews conducted with 10 senior nurse leaders between August 2011 and
      March 2012. The analytic method was developed by the Brazilian phenomenologist,
      Martins. FINDINGS: Senior nurse leaders described how they critically appraise
      many sources of evidence when making managerial decisions. They emphasized the
      importance of working with their teams to locally adapt and evaluate best
      evidence associated with managerial decision making and organizational
      innovations. Their statements also demonstrated how they use evidence-based
      management to support the adoption of evidence-based practices. They did not,
      however, provide specific strategies for seeking out and obtaining evidence.
      Notable challenges were traditional cultures and rigid bureaucracies, while major
      facilitators included accreditation, teamwork, and shared decision making.
      CONCLUSIONS: Evidence-based management necessitates a continuous process of
      locating, implementing, and evaluating evidence. In this study leaders provided
      multiple, concrete examples of all these processes except seeking out and
      locating evidence. They also gave examples of other leadership skills associated
      with successful adoption of evidence-based practice and management, particularly
      interdisciplinary teamwork and shared decision making. CLINICAL RELEVANCE: This
      study demonstrates senior nurse leaders' awareness and utilization of evidence
      based management. The study also suggests what aspects of evidence-based
      management need further development, such as more active identification of
      potential, new organizational innovations.

PMID- 23530972
TI  - The missing skill set in community management of tropical forests.

PMID- 23530973
TI  - Analysis of phenolic compounds in Portuguese wild and commercial berries after
      multienzyme hydrolysis.
AB  - Berry fruits are a good source of phenolic compounds and thus, potentially
      beneficial to health. Phenolic compounds are mainly present as a variety of
      conjugated forms, either with sugars via O-glycosidic bonds or with other polyols
      as esters. This chemodiversity makes characterization and identification highly
      demanding. Selected varieties of commercial blueberries, raspberries and
      blackberries and the two wild berries Portuguese crowberry and strawberry tree
      fruits were characterized for individual phenolic content by liquid
      chromatography-diode array detection and mass spectrometry (HPLC-DAD-MS) after
      hydrolysis by a novel combination of the fungal glycosidases hesperidinase and
      cellulase. This approach is shown to be a simple alternative to other existing
      methods for analysis of plant phenolic compound aglycones. The hydrolysis of
      glycosides and organic acid esters is efficient and less aggressive than acid and
      alkaline hydrolysis. This method is able to disclose new sources of dietary
      phenolic compounds, and the potential usefulness of Portuguese crowberry and
      strawberry tree fruit is herein demonstrated. 

PMID- 23530974
TI  - Endogenous cholinergic tone modulates spontaneous network level neuronal activity
      in primary cortical cultures grown on multi-electrode arrays.
AB  - BACKGROUND: Cortical cultures grown long-term on multi-electrode arrays (MEAs)
      are frequently and extensively used as models of cortical networks in studies of
      neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying
      synaptic plasticity. However, in contrast to the predominantly asynchronous
      neuronal firing activity exhibited by intact cortex, electrophysiological
      activity of mature cortical cultures is dominated by spontaneous epileptiform
      like global burst events which hinders their effective use in network-level
      studies, particularly for neurally-controlled animat ('artificial animal')
      applications. Thus, the identification of culture features that can be exploited
      to produce neuronal activity more representative of that seen in vivo could
      increase the utility and relevance of studies that employ these preparations.
      Acetylcholine has a recognised neuromodulatory role affecting excitability,
      rhythmicity, plasticity and information flow in vivo although its endogenous
      production by cortical cultures and subsequent functional influence upon neuronal
      excitability remains unknown. RESULTS: Consequently, using MEA
      electrophysiological recording supported by immunohistochemical and RT-qPCR
      methods, we demonstrate for the first time, the presence of intrinsic cholinergic
      neurons and significant, endogenous cholinergic tone in cortical cultures with a
      characterisation of the muscarinic and nicotinic components that underlie
      modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh
      receptor (mAChR) activation affects global excitability and burst event
      regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic
      ACh receptor (nAChR) activation can modulate burst duration and the proportion of
      spikes occurring within bursts in a spatio-temporal fashion. CONCLUSIONS: We
      suggest that the presence of significant endogenous cholinergic tone in cortical
      cultures and the comparability of its modulatory effects to those seen in intact
      brain tissues support emerging, exploitable commonalities between in vivo and in
      vitro preparations. We conclude that experimental manipulation of endogenous
      cholinergic tone could offer a novel opportunity to improve the use of cortical
      cultures for studies of network-level mechanisms in a manner that remains largely
      consistent with its functional role.

PMID- 23530975
TI  - Engineering buffering and hydrolytic or photolabile charge shifting in a
      polycarboxybetaine ester gene delivery platform.
AB  - Polycarboxybetaine esters (PCB-esters) can condense plasmid DNA into nanosized
      polyplexes for highly effective gene delivery with low toxicity. The design and
      characterization of tertiary CB-ester monomers and PCB-ester polymers are
      presented here to study the effects of molecular variation on functions important
      to nonviral gene transfer. Both buffering capacity and charge-shifting behavior
      can be tuned by modifying the distance between the charged groups and the ester
      size or type. A carbon spacer length (CSL) of one was found to bring the pKa of
      the tertiary amine into the optimal range for proton buffering. Ester hydrolytic
      degradation switches this polymer from cationic (DNA binding) to zwitterionic
      (DNA releasing) form while conferring nontoxicity. To allow rapid and externally
      controlled degradation, the effect of this charge-switching behavior on DNA
      release from polyplexes was directly studied with a novel photolabile PCB
      nitrobenzyl ester (PCB-NBE). Photoinitiated ester degradation precipitated the
      rapid release of 72+/-5% of complexed DNA from PCB-NBE polyplexes. These insights
      reveal the key parameters important for the PCB-ester platform and the
      significance of charge switching to an effective and nontoxic nonviral gene
      delivery platform.

PMID- 23530976
TI  - Relationships amongst osteoarthritis biomarkers, dynamic knee joint load, and
      exercise: results from a randomized controlled pilot study.
AB  - BACKGROUND: Little is known about the relationships of circulating levels of
      biomarkers of cartilage degradation with biomechanical outcomes relevant to knee
      osteoarthritis (OA) or biomarker changes following non-pharmacological
      interventions. The objectives of this exploratory, pilot study were to: 1)
      examine relationships between biomarkers of articular cartilage degradation and
      synthesis with measures of knee joint load during walking, and 2) examine changes
      in these biomarkers following 10 weeks of strengthening exercises. METHODS:
      Seventeen (8 male, 9 female; 66.1 +/- 11.3 years of age) individuals with
      radiographically-confirmed medial tibiofemoral OA participated. All participants
      underwent a baseline testing session where serum and urine samples were
      collected, followed by a three-dimensional motion analysis. Motion analysis was
      used to calculate the external knee adduction moment (KAM) peak value and
      impulse. Following baseline testing, participants were randomized to either 10
      weeks of: 1) physiotherapist-supervised lower limb muscle strengthening
      exercises, or 2) no exercises (control). Identical follow-up testing was
      conducted 11 weeks after baseline. Biomarkers included: urinary C-telopeptide of
      type II collagen (uCTX-II) and type II collagen cleavage neoepitope (uC2C), serum
      cartilage oligomeric matrix protein (sCOMP), serum hyaluronic acid (sHA) and
      serum C-propeptide of type II procollagen (sCPII). Linear regression analysis was
      used to examine relationships between measures of the KAM and biomarker
      concentrations as baseline, as well as between-group differences following the
      intervention. RESULTS: KAM impulse predicted significant variation in uCTX-II
      levels at baseline (p = 0.04), though not when controlling for disease severity
      and walking speed (p = 0.33). KAM impulse explained significant variation in the
      ratio uCTX-II;sCPII even when controlling for additional variables (p = 0.04).
      Following the intervention, changes in sCOMP were significantly greater in the
      exercise group compared to controls (p = 0.04). On average those in the control
      group experienced a slight increase in sCOMP and uCTX-II, while those in the
      exercise group experienced a reduction. No other significant findings were
      observed. CONCLUSIONS: This research provides initial evidence of a potential
      relationship between uCTX-II and knee joint load measures in patients with medial
      tibiofemoral knee OA. However, this relationship became non-significant after
      controlling for disease severity and walking speed, suggesting further research
      is necessary. It also appears that sCOMP is amenable to change following a
      strengthening intervention, suggesting a potential beneficial role of exercise on
      cartilage structure. TRIAL REGISTRATION: Clinicaltrials.gov NCT01241812.

PMID- 23530977
TI  - Control of home blood pressure with an amlodipine- or losartan-based regimen and
      progression of carotid artery intima-media thickness in hypertensive patients:
      the HOSP substudy.
AB  - Carotid artery intima-media thickness (IMT) has emerged as a predictor of
      cardiovascular events. Home blood pressure (BP) is more closely associated with
      cardiovascular prognosis than clinic BP. The aim of this study was to compare the
      progression of carotid IMT with respect to strict and mild control of morning
      home systolic BP (SBP) and amlodipine- and losartan-based antihypertensive
      therapy in hypertensive patients. Subjects included 80 hypertensive outpatients
      who participated in the Hypertension Control Based on Home Systolic Pressure
      (HOSP) pilot study. After a 1-month drug-free period, the patients were randomly
      assigned to either the strict control group (target SBP <130 mm Hg) or the mild
      control group (130-139 mm Hg) and to either the amlodipine group or the losartan
      group. Additional antihypertensive drugs were added if target BP was not achieved
      with monotherapy. Morning SBP achieved target levels during 5 years in the strict
      control group and in the mild control group, while it was comparable between
      amlodipine and losartan groups. In all patients, mean and maximum carotid IMT
      increased significantly. Changes in carotid IMT did not differ between strict and
      mild control groups. Changes in mean carotid IMT in amlodipine group were smaller
      than those in losartan group at year 1, but were not different between the two
      groups at year 5. In conclusion, carotid IMT increased over time in hypertensive
      patients in spite of the strict control of home BP. Amlodipine may slow the
      progression of IMT more than losartan, although a difference was not obvious
      after 5 years.

PMID- 23530978
TI  - Repeat liver resection for recurrent colorectal metastases: a single-centre, 13
      year experience.
AB  - OBJECTIVES: Isolated intrahepatic recurrence is noted in up to 40% of patients
      following curative liver resection for colorectal liver metastases (CLM). The
      aims of this study were to analyse the outcomes of repeat hepatectomy for
      recurrent CLM and to identify factors predicting survival. METHODS: Data for all
      liver resections for CLM carried out at one centre between 1998 and 2011 were
      analysed. RESULTS: A total of 1027 liver resections were performed for CLM. Of
      these, 58 were repeat liver resections performed in 53 patients. Median time
      intervals were 10.5 months between the primary resection and first hepatectomy,
      and 15.4 months between the first and repeat hepatectomies. The median tumour
      size was 3.0 cm and the median number of tumours was one. Six patients had a
      positive margin (R1) resection following first hepatectomy. There were no
      perioperative deaths. Significant complications included transient liver
      dysfunction in one and bile leak in two patients. Rates of 1-, 3- and 5-year
      overall survival following repeat liver resection were 85%, 61% and 52%,
      respectively, at a median follow-up of 23 months. R1 resection at first
      hepatectomy (P = 0.002), a shorter time interval between the first and second
      hepatectomies (P = 0.02) and the presence of extrahepatic disease (P = 0.02) were
      associated with significantly worse overall survival. CONCLUSIONS: Repeat
      resection of CLM is safe and can achieve longterm survival in carefully selected
      patients. A preoperative knowledge of poor prognostic factors helps to facilitate
      better patient selection.

PMID- 23530979
TI  - The role of self-regulating abilities in long-term weight loss in severely obese
      children and adolescents undergoing intensive combined lifestyle interventions
      (HELIOS); rationale, design and methods.
AB  - BACKGROUND: Adequate treatment of severe childhood obesity is important given its
      serious social, psychological and physical consequences. Self-regulation may be a
      crucial determinant of treatment success. Yet, little is known about the role
      that self-regulation and other psychosocial factors play in the long-term outcome
      of obesity treatment in severely obese children and adolescents.In this paper, we
      describe the design of a study that aims to determine whether the ability to self
      regulate predicts long-term weight loss in severely obese children and
      adolescents. An additional objective is to identify other psychosocial factors
      that may modify this relation. METHODS/DESIGN: The study is designed as a
      prospective observational study of 120 severely obese children and adolescents (8
      19 years) and their parents/caregivers undergoing an intensive combined lifestyle
      intervention during one year. The intervention uses behavior change techniques to
      improve the general ability to self-regulate.Measurements will be taken at three
      points in time: at baseline (start of treatment), at the end of treatment (1 year
      after baseline) and at follow-up (2 years after baseline). The primary outcome
      measurement is the gender and age-specific change in SDS-BMI.The children's
      general self-regulation abilities are evaluated by two behavioral computer tasks
      assessing two distinct aspects of self-regulation that are particularly relevant
      to controlling food intake: inhibitory control (Stop Signal Task) and sensitivity
      to reward (Balloon Analogue Risk Task). In addition to the computer tasks, a self
      report measure of eating-specific self-regulation ability is used. Psychosocial
      factors related to competence, motivation, relatedness and outcome expectations
      are examined as moderating factors using several questionnaires for the patients
      and their parents/caregivers. DISCUSSION: This study will provide knowledge about
      the relation between self-regulation and long-term weight loss after intensive
      lifestyle interventions over a two-year period in severely obese children and
      adolescents, a growing but often overlooked patient group. We aim to investigate
      to what extent (changes in) the general ability to self-regulate predicts weight
      loss and weight loss maintenance. This study will also contribute to the
      knowledge on how this association is modified by other psychosocial factors. The
      results may contribute to the development of more successful interventions. TRIAL
      REGISTRATION: Netherlands Trial Register (NTR1678, registered 20-Feb-2009).

PMID- 23530980
TI  - Rate and predictors of non-AIDS events in a cohort of HIV-infected patients with
      a CD4 T cell count above 500 cells/mm3.
AB  - The reduction of risk of non-AIDS events after combined antiretroviral therapy
      (cART) initiation and the crude incidence rate (CIR) of these events in patients
      who control the viral load without cART (controllers) in a cohort of 574
      antiretroviral-naive patients with a baseline CD4 T cell count above 500
      cells/mm3 were assessed. Non-AIDS severe events were defined as a first admission
      to the hospital due to non-AIDS-defining malignancies, cardiovascular,
      neuropsychiatric, liver-related, or end-stage renal disease events. Potential
      determinants of non-AIDS/death events were studied using Cox regression models.
      Eighty-five non-AIDS/death events occurred during 6,062 persons-years of follow
      up (PYFU) with a CIR of 1.4 per 100 PYFU. Factors associated with non-AIDS/death
      event were age (HR 3.4; 95% CI: 1.6-6.9), nadir CD4 below 350 cells/mm3 (HR 2.5;
      95% CI: 1.4-4.6), and a last determination of viral load above the median (HR
      1.9; 95% CI: 1.0-3.3). The CIR of non-AIDS/death events was 2.1 and 1.8 per 100
      PYFU before and after cART in patients who started cART (n=446). A reduction of
      CIR of non-AIDS events after cART initiation was observed only in patients with a
      nadir of CD4 above 350 cells/mm3 (2.5 vs. 0.6 per 100 PYFU, p=0.004, and remained
      stable after cART in patients with a median nadir of CD4 below 350 cells/mm3. CIR
      was similar in elite, viremic, and noncontrollers (1.1, 1.0, and 1.5 per 100
      PYFU, respectively, p=0.25). Reduction of CIR of non-AIDS events after cART
      initiation depends on nadir CD4 T cell count. Most of the controllers patients
      had a CIR similar to noncontrollers. These data support the early initiation of
      cART in HIV-infected patients.

PMID- 23530981
TI  - Incidental discovery of circle contact lens by MRI: you can't scan my poker face,
      circle contact lens as a potential MRI hazard.
AB  - BACKGROUND: Circle contact lenses, also known as color contact lenses and big eye
      contact lenses, are a type of cosmetic contact lens. It is not generally known
      that a circle contact lens usually contains iron oxide and other metals, which
      means their use during magnetic resonance imaging (MRI) is a potential hazard.
      CASE PRESENTATION: We present a rare case of incidental discovery of circle
      contact lenses by MRI and MRI images of circle lenses in vitro. CONCLUSIONS:
      Circle contact lenses usually contain iron oxide, which is a known source of
      susceptibility artifact on MRI. Not only radiologists and radiographers but also
      referring physicians should be familiar with the imaging findings and potential
      risk of scanning circle contact lenses by MRI.

PMID- 23530982
TI  - Bone cement-induced pulmonary embolism in a myeloma patient.

PMID- 23530983
TI  - Correlations between serum levels of beta amyloid, cerebrospinal levels of tau
      and phospho tau, and delayed response tasks in young and aged cynomolgus monkeys
      (Macaca fascicularis).
AB  - BACKGROUND: In an attempt to explore cynomolgus monkeys as an animal model for
      Alzheimer's disease, the present study focused on the Alzheimer's biomarkers beta
      amyloid 1-42 (Abeta42 ) in serum, and total tau (t-tau) and phosphorylated tau (p
      tau) levels in cerebrospinal fluid. METHODS: We measured biomarker levels in
      Young and Aged cynomolgus monkeys and correlated these with performance on three
      delayed response tasks. RESULTS: The Abeta42 concentration of the Aged monkeys
      was significantly lower than in the Young subjects, while the t-tau and p-tau did
      not significantly differ between the groups. The Young subjects performed
      significantly better than the Aged individuals on the memory tests. Only Abeta42
      levels were significantly correlated with performance in the three delayed
      response tasks. CONCLUSIONS: Circulating Abeta42 levels were lower in Aged
      monkeys and were correlated with inferior performance on delayed response tasks
      in Aged animals; therefore, both measures may be useful in establishing
      cynomolgus monkeys as models for studies of AD.

PMID- 23530984
TI  - Weight, body image and bullying in 9-year-old children.
AB  - AIM: To explore the association between weight and bullying; considering victims
      and perpetrators as two aspects of bullying, and subjective perception and
      objective measurement as two aspects of weight. METHODS: This study is based on
      the first wave of data collection from Growing Up in Ireland - the National
      Longitudinal Study of Children. The two-stage sample design included a sample of
      910 primary schools in Ireland, from which a sample of 8568 nine-year-old
      children and their families was randomly selected. Analysis is based on
      statistically reweighted data to ensure that it is representative of all 9-year
      olds in Ireland. RESULTS: Significantly (P < 0.001) more girls were overweight or
      obese (33.1%: 23.1% overweight and 10% obese) than boys (25.2%: 18.3% and 6.9%).
      Children who were body mass index (BMI) classified as overweight or obese were
      significantly (P < 0.001) more likely to be victimised when compared with
      children whose BMI was not classified as overweight or obese. BMI-classified
      thinness was not significantly associated with victimisation; however, the body
      image of being skinny or very skinny was significantly (P = 0.015) associated
      with being victimised. Bullying perpetration was not associated with BMI-derived
      weight classification but was significantly (P < 0.001) associated with the
      child's own self-description of weight. CONCLUSIONS: Overall body image was found
      to have a stronger association with victimisation and bullying perpetration than
      objective BMI-derived weight classification. Further research investigating the
      mediating role of body image in the relationship between weight, victimisation
      and bullying is necessary to better understand this association.

PMID- 23530985
TI  - A transactional and collaborative approach to reducing effects of bottom
      trawling.
AB  - Private-sector financial and legal transactions have long been used to protect
      terrestrial habitats and working landscapes, but less commonly to address
      critical threats in marine environments. Transferrable and marketable fishing
      privileges, including permits and quotas, make it possible to use private-sector
      transactions as conservation strategies to address some fishery management
      issues. Abating the effects of bottom trawling on the seafloor and bycatch and
      discard associated with the practice has proven challenging. On the Central Coast
      of California, The Nature Conservancy (TNC), Environmental Defense Fund, local
      fishers and local, state, and federal authorities worked collaboratively to
      protect large areas of the seafloor from bottom trawling for groundfish while
      addressing economic impacts of trawl closures. Contingent on the adoption of
      trawl-closure areas by a federal regulatory agency, TNC used private funds to
      purchase federal groundfish trawl permits and vessels from willing sellers. Trawl
      closure areas were designed collaboratively by combining regional biological
      diversity and fisheries data with local fishers' knowledge. The private
      transactional strategy was designed to remedy some deficiencies in previous
      federal buyouts, to mitigate economic impacts from trawl closures, and to
      carefully align with a public regulatory process to protect "essential fish
      habitat" under the Magnuson-Stevens Fishery Conservation and Management Act. This
      collaborative effort protected 1.5 million ha (3.8 million acres) of seafloor,
      reduced trawl effort in the area by 50%, and set a precedent for collaborative
      partnerships between conservation and fishing interests. This is the first time a
      large conservation organization has taken an ownership position in a fishery and
      demonstrates how nongovernmental organizations can invest in fisheries to improve
      environmental and economic performance.

PMID- 23530986
TI  - Elucidating phytochemical production in Juniperus sp.: seasonality and response
      to stress situations.
AB  - Phenolic-enriched extracts from Portuguese junipers were described as potential
      neuroprotective natural products. However, evaluation of plants for
      pharma/nutraceutical industry is based on secondary metabolite content, which is
      influenced by the environmental conditions. Therefore, it became important to
      elucidate the metabolic response of the junipers to seasonality and to stress
      conditions with regard to polyphenol production. Seasonal conditions modulated
      total phenolic and flavonoids contents of the four juniper species. Higher levels
      of phytochemicals were obtained when plants were not actively growing. However,
      only a few differences were registered in the relative contents of psydrin and a
      procyanidin dimer, according to species. Salt stress and methyl jasmonate
      elicitation promote different responses within the species. They were effective
      in enhancing phenolic accumulation, with just a few alterations in the relative
      contents of procyanidins, epicatechin, and quercetin derivatives. These
      differences were also reflected in gene expression of important enzymes from
      biosynthetic pathways. 

PMID- 23530987
TI  - Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of
      oral anticoagulant treatment: dose-response relationship in healthy volunteers.
AB  - BACKGROUND AND OBJECTIVE: Despite the worldwide use of vitamin K antagonists
      (VKAs), there is limited knowledge of the influence of dietary vitamin K on
      anticoagulation control. In view of the increasing nutraceutical availability of
      menaquinone-7 (MK-7; vitamin K2 ) and its promotion for bone and cardiovascular
      health, it is important to determine the posology for the interference of
      supplemental MK-7 with VKA therapy. PATIENTS: Eighteen healthy men and women were
      anticoagulated for 4 weeks with acenocoumarol, and 15 of them attained a target
      International Normalized Ratio (INR) of 2.0. In the six subsequent weeks,
      subjects were given increasing doses of MK-7 (10, 20 and 45 MUg day(-1) ) while
      continuing acenocoumarol treatment at established individual doses. RESULTS:
      Apart from the INR, acenocoumarol treatment significantly increased the levels of
      uncarboxylated factor II (ucFII), uncarboxylated osteocalcin (ucOC), and
      desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP), and decreased endogenous
      thrombin generation (ETP). A daily intake of 45 MUg of MK-7 significantly
      decreased the group mean values of both the INR and ucFII by ~ 40%. Daily intakes
      of 10 and 20 MUg of MK-7 were independently judged by two hematologists to cause
      a clinically relevant lowering of the INR in at least 40% and 60% of subjects,
      respectively, and to significantly increase ETP by ~ 20% and ~ 30%, respectively.
      Circulating ucOC and dp-ucMGP were not affected by MK-7 intake. CONCLUSIONS: MK-7
      supplementation at doses as low as 10 MUg (lower than the usual retail dose of 45
      MUg) significantly influenced anticoagulation sensitivity in some individuals.
      Hence, the use of MK-7 supplements needs to be avoided in patients receiving VKA
      therapy.

PMID- 23530989
TI  - Immunopathological characteristics of patients with bullous pemphigoid and
      neurological disease.
AB  - BACKGROUND: The relationship between bullous pemphigoid (BP) and neurological
      disease has been the subject of numerous recent studies and BP antigens and their
      isoforms have been identified in the central nervous system (CNS). Whilst
      epidemiological data support this association, little is known about the
      pathomechanism behind this link and the immunological characteristics of patients
      with BP and neurological disease, other than multiple sclerosis (MS), has not
      been studied. OBJECTIVE: We aimed to compare the cutaneous immune response in BP
      patients with and without neurological disease, to investigate whether or not
      there is a distinctive immunopathological profile in patients with concomitant BP
      and neurological disease. METHODS: Seventy-two patients with BP were included and
      divided into two groups; those with neurological disease (BP+N, n = 43) and those
      without (BP-N, n = 29). Patients in BP+N group had a confirmed neurological
      disease by a hospital physician, neurologist or psychiatrist with positive
      neurological imaging where appropriate, or a Karnofsky score of 50 or less due to
      mental impairment. All sera were analysed with indirect immunofluorescence (IIF)
      using serial dilutions up to 1:120000, immunoblotting (IB) and Enzyme-linked
      immunosorbent assay (ELISA) for BP180 and BP230. RESULTS: Median antibody titres
      by IIF were 1:1600 vs. 1:800 for BP-N and BP+N, respectively, although the
      difference did not reach statistic significance (P = 0.93, Mann-Whitney U-test).
      ELISA values for both BP180 and BP230 did not differ significantly between the
      two groups. Similarly, autoantibodies to specific antigens as identified by ELISA
      and IB were not related to the presence of neurological disease. CONCLUSION: The
      results of this study indicate that patients with BP and neurological disease
      exhibit an immune response to both BP180 and BP230, thus the link between the CNS
      and the skin is not dependent on a specific antigen, but possibly both antigens
      or their isoforms may be exposed following a neurological insult, and play a role
      in generation of an immune response.

PMID- 23530988
TI  - Mixtures of xenoestrogens disrupt estradiol-induced non-genomic signaling and
      downstream functions in pituitary cells.
AB  - BACKGROUND: Our study examines the effects of xenoestrogen mixtures on estradiol
      induced non-genomic signaling and associated functional responses. Bisphenol-A,
      used to manufacture plastic consumer products, and nonylphenol, a surfactant, are
      estrogenic by a variety of assays, including altering many intracellular
      signaling pathways; bisphenol-S is now used as a bisphenol-A substitute. All
      three compounds contaminate the environment globally. We previously showed that
      bisphenol-S, bisphenol-A, and nonylphenol alone rapidly activated several kinases
      at very low concentrations in the GH3/B6/F10 rat pituitary cell line. METHODS:
      For each assay we compared the response of individual xenoestrogens at
      environmentally relevant concentrations (10-15 -10-7 M), to their mixture effects
      on 10-9 M estradiol-induced responses. We used a medium-throughput plate
      immunoassay to quantify phosphorylations of extracellular signal-regulated
      kinases (ERKs) and c-Jun-N-terminal kinases (JNKs). Cell numbers were assessed by
      crystal violet assay to compare the proliferative effects. Apoptosis was assessed
      by measuring caspase 8 and 9 activities via the release of the fluorescent
      product 7-amino-4-trifluoromethylcoumarin. Prolactin release was measured by
      radio-immunoassay after a 1 min exposure to all individual and combinations of
      estrogens. RESULTS: Individual xenoestrogens elicited phospho-activation of ERK
      in a non-monotonic dose- (fM-nM) and mostly oscillating time-dependent (2.5-60
      min) manner. When multiple xenoestrogens were combined with nM estradiol, the
      physiologic estrogen's response was attenuated. Individual bisphenol compounds
      did not activate JNK, while nonylphenol did; however, the combination of two or
      three xenoestrogens with estradiol generated an enhanced non-monotonic JNK dose
      response. Estradiol and all xenoestrogen compounds induced cell proliferation
      individually, while the mixtures of these compounds with estradiol suppressed
      proliferation below that of the vehicle control, suggesting a possible apoptotic
      response. Extrinsic caspase 8 activity was suppressed by estradiol, elevated by
      bisphenol S, and unaffected by mixtures. Intrinsic caspase 9 activity was
      inhibited by estradiol, and by xenoestrogen combinations (at 10-14 and 10-8 M).
      Mixtures of xenoestrogens impeded the estradiol-induced release of prolactin.
      CONCLUSIONS: In mixtures expected to be found in contaminated environments,
      xenoestrogens can have dramatic disrupting effects on hormonal mechanisms of cell
      regulation and their downstream functional responses, altering cellular responses
      to physiologic estrogens.

PMID- 23530990
TI  - Structure, bioactivity, and chemical synthesis of OSW-1 and other steroidal
      glycosides in the genus Ornithogalum.

PMID- 23530991
TI  - Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A
      randomized, double-blind, placebo-controlled trial.
AB  - AIM: Liver cirrhosis represents the end stage of any chronic liver disease, and
      it is associated with hepatic edema such as ascites. Many patients with ascites
      do not respond to diuretic therapy or require administration of diuretics at high
      doses that can cause adverse events. This 7-day, multicenter, double-blind trial
      of tolvaptan was designed to determine the optimal dose of tolvaptan for
      producing the intended pharmacological effect in hepatic edema. METHODS: Liver
      cirrhosis patients with inadequate diuretic response despite having received a
      conventional diuretic therapy were enrolled in the trial. Participants were
      stratified randomly to four groups receiving tolvaptan at 7.5, 15 or 30 mg/day,
      or placebo as an add-on to conventional diuretics once daily for 7 days. Changes
      in bodyweight and abdominal circumference were analyzed. Serum sodium
      concentrations were measured. Safety assessment was performed. RESULTS: Tolvaptan
      at 7.5-30 mg/day reduced bodyweight and abdominal circumference compared with
      placebo. Serum sodium concentrations remained within the normal range in all
      tolvaptan groups. Serious adverse events were not observed, and most common
      adverse event was thirst. Tolvaptan at 7.5 mg/day showed the maximum change in
      bodyweight and abdominal circumference together with preferable tolerability.
      CONCLUSION: Tolvaptan at 7.5 mg/day was considered the optimal dose in liver
      cirrhosis patients with hepatic edema who showed inadequate response to
      conventional diuretics.

PMID- 23530992
TI  - Thyroid hormone status and health-related quality of life in the LifeLines Cohort
      Study.
AB  - BACKGROUND: Thyroid disorders are prevalent in Western society, yet many subjects
      experience limited symptoms at diagnosis, especially in hypothyroidism. We
      hypothesize that health-related quality of life (HR-QOL) is more severely
      impaired in subjects with more abnormal thyroid hormone function tests. METHODS:
      This is a cross-sectional study of Dutch adults participating in the LifeLines
      Cohort Study between December 2009 and August 2010. In 9491 Western European
      participants (median age 45 years; 3993 men and 5498 women), without current or
      former use of thyroid medication, we compared HR-QOL using the RAND 36-Item
      Health Survey between subjects with normal thyrotropin (TSH) values and subjects
      with disturbed thyroid hormone status (serum TSH, free thyroxine, and free
      triiodothyronine). The influence of possible confounders (age, smoking, co
      morbidity) on HR-QOL was evaluated as well. RESULTS: Suppressed TSH values (TSH <
      0.5 mU/L) were found in 114 (1.2%), while 8334 (88.8%) had TSH within the normal
      range, 973 participants (10.3%) had TSH between 4 and 10 mU/L, and 70 (0.7%) had
      TSH > 10 mU/L. Men had a higher HR-QOL than women (70-92 vs. 65-89; p < 0.001),
      except for the domain "general health" (72 vs. 72; p = 0.692). Men with
      suppressed or elevated TSH values did not score significantly lower than
      euthyroid men for any of nine domains of the RAND 36-Item Health Survey. Compared
      with euthyroid women, women with suppressed TSH scored significantly lower in the
      domains "physical functioning" (84 vs. 89, p = 0.013) and "general health" (67
      vs. 72, p = 0.036). Women with markedly elevated TSH (> 10 mU/L) had a score in
      all HR-QOL domains that was similar to that of women with normal TSH values.
      There were no differences in the physical component score and the mental
      component score between any of the TSH groups. Physical component score and
      mental component score were mainly determined by smoking status, co-morbidity,
      and body mass index or waist circumference. CONCLUSIONS: In this population-based
      study, HR-QOL scores of subjects with suppressed TSH values or markedly elevated
      TSH values were generally not significantly lower than those of subjects with
      normal or mildly elevated TSH values.

PMID- 23530993
TI  - In vivo thyroid vibro-acoustography: a pilot study.
AB  - BACKGROUND: The purpose of this study was to evaluate the utility of a
      noninvasive ultrasound-based method, vibro-acoustography (VA), for thyroid
      imaging and determine the feasibility and challenges of VA in detecting nodules
      in thyroid. METHODS: Our study included two parts. First, in an in vitro study,
      experiments were conducted on a number of excised thyroid specimens randomly
      taken from autopsy. Three types of images were acquired from most of the
      specimens: X-ray, B-mode ultrasound, and vibro-acoustography. The second and main
      part of the study includes results from performing VA and B-mode ultrasound
      imaging on 24 human subjects with thyroid nodules. The results were evaluated and
      compared qualitatively. RESULTS: In vitro vibro-acoustography images displayed
      soft tissue structures, microcalcifications, cysts and nodules with high contrast
      and no speckle. In this group, all of US proven nodules and all of X-ray proven
      calcifications of thyroid tissues were detected by VA. In vivo results showed
      100% of US proven calcifications and 91% of the US detected nodules were
      identified by VA, however, some artifacts were present in some cases.
      CONCLUSIONS: In vitro and in vivo VA images show promising results for
      delineating the detailed structure of the thyroid, finding nodules and in
      particular calcifications with greater clarity compare to US. Our findings
      suggest that, with further development, VA may be a suitable imaging modality for
      clinical thyroid imaging.

PMID- 23530995
TI  - Repeatability of autofluorescence lifetime imaging at the human fundus in healthy
      volunteers.
AB  - PURPOSE: We aim to evaluate the repeatability of a new fluorescence lifetime
      imaging (FLIM) technique which measures time-resolved autofluorescence to assess
      metabolism of the retina. MATERIALS AND METHODS: We performed FLIM with two
      spectral channels (channel 1: 490-560 nm and channel 2: 560-700 nm) on 10 healthy
      volunteers, with 10 replicates per volunteer. From the 30 degrees  fundus FLIM
      images, we selected three regions: the fovea, the optic disc and the papillo
      macular bundle. For each channel in these regions, we determined an average multi
      exponential approximation with three components, and the six resulting
      parameters, alpha1-alpha3 (amplitudes) and tau1-tau3 (fluorescence lifetimes),
      were analyzed in terms of the coefficient of variation (CV). RESULTS:
      Repeatability was highest in the papillo-macular bundle, followed by the fovea
      and the optic disc. Repeatability was higher in channel 1 (mean CV of 7.9%) than
      in channel 2 (mean CV of 17.7%). The average CV for the diagnostically most
      relevant channel 1 and the most relevant parameters was as follows: tau1 (5.5%)
      and tau2 (4.7%) in the papillo-macular bundle, and tau1 (6.8%) and tau2 (6.9%) in
      the fovea. CONCLUSIONS: We demonstrated repeatability of FLIM measurement results
      within acceptable ranges of variation. Based on the detailed coefficients of
      variation, we derived recommendations for parameter ranges suitable for
      diagnostic applications.

PMID- 23530994
TI  - Analysis of muscle fiber conduction velocity enables reliable detection of
      surface EMG crosstalk during detection of nociceptive withdrawal reflexes.
AB  - BACKGROUND: The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal
      reflex that induces complex muscle synergies to withdraw a limb from a potential
      noxious stimulus. Several studies indicate that assessment of the NWR is a
      valuable objective tool in relation to investigation of various pain conditions.
      However, existing methodologies for NWR assessment evaluate standard surface
      electromyography (sEMG) measured over just one muscle and do not consider the
      possible interference of crosstalk originating from adjacent active muscles. The
      present study had two aims: firstly, to investigate to which extent the presence
      of crosstalk may affect NWR detection using a standardized scoring criterion
      (interval peak z-score) that has been validated without taking crosstalk into
      consideration. Secondly, to investigate whether estimation of muscle fiber
      conduction velocity can help identifying the propagating and non-propagating
      nature of genuine reflexes and crosstalk respectively, thus allowing a more valid
      assessment of the NWR. RESULTS: Evaluation of interval peak z-score did
      apparently allow reflex detection with high sensitivity and specificity (0.96),
      but only if the influence of crosstalk was ignored. Distinction between genuine
      reflexes and crosstalk revealed that evaluation of interval peak z-score
      incorporating a z-score threshold of 12 was associated with poor reflex detection
      specificity (0.26-0.62) due to the presence of crosstalk. Two different
      standardized methods for estimation of muscle fiber conduction velocity were
      employed to demonstrate that significantly different muscle fiber conduction
      velocities may be estimated during genuine reflexes and crosstalk, respectively.
      This discriminative feature was used to develop and evaluate a novel methodology
      for reflex detection from sEMG that is robust with respect to crosstalk.
      Application of this conduction velocity analysis (CVA) entailed reflex detection
      with excellent sensitivity (1.00 and 1.00) and specificity (1.00 and 0.96) for
      the tibialis anterior and soleus muscles. CONCLUSION: This study investigated the
      negative effect of electrical crosstalk during reflex detection and revealed that
      the use of a previously validated scoring criterion may result in poor
      specificity due to crosstalk. The excellent performance of the developed
      methodology in the presence of crosstalk shows that assessment of muscle fiber
      conduction velocity allows reliable detection of EMG crosstalk during reflex
      detection.

PMID- 23530996
TI  - Working group consultation: alloimmunity as a vaccine approach against HIV/AIDS:
      National Institutes of Health Meeting Report, May 24, 2012.
AB  - Alloimmunization vaccine strategies propose to avoid the problem of the extreme
      antigenic variability of human immunodeficiency virus (HIV) by instead focusing
      on the cellular antigens incorporated into HIV virions as they bud from infected
      cells. This report summarizes a Consultation meeting convened by the National
      Institute of Allergy and Infectious Diseases, National Institutes of Health on
      May 24, 2012. The objectives of the meeting were to (1) reach a consensus on the
      essential questions surrounding alloimmunization as a strategy for vaccine design
      against HIV, and (2) determine the experimental elements that might be needed for
      addressing these questions in an optimized pilot framework nonhuman primate (NHP)
      protocol for allogeneic immunization. The Consultation revisited the rationale
      and concerns of vaccination to induce allogeneic immunity, one of the most potent
      natural immune responses. The panelists' consensus was that a carefully designed
      skin graft transplant pilot experiment, in major histocompatibility complex (MHC)
      disparate male Mauritian cynomolgus macaques (MCM; Macaca fascicularis), would be
      useful for initially evaluating if alloimmunization results in an effective or
      even a partially effective safe AIDS vaccine. A successful NHP study for
      allogeneic immunization would provide further opportunities to explore vaccine
      elicited immune and genetic correlates of protection against the acquisition of
      viral infection.

PMID- 23530997
TI  - Molecular, genetic, cellular, and network functions in the spinal cord and
      brainstem.
AB  - Studies of the model systems of spinal cord and brainstem reveal molecular,
      genetic, and cellular mechanisms that are critical for network and behavioral
      functions in the nervous system. Recent experiments establish the importance of
      neurogenetics in revealing cellular and network properties. Breakthroughs that
      utilize direct visualization of neuronal activity and network structure provide
      new insights. Major discoveries of plasticity in the spinal cord and brainstem
      contribute to basic neuroscience and, in addition, have promising therapeutic
      implications.

PMID- 23530998
TI  - Neurotransmitters and synaptic components in the Merkel cell-neurite complex, a
      gentle-touch receptor.
AB  - Merkel cells are an enigmatic group of rare cells found in the skin of
      vertebrates. Most make contacts with somatosensory afferents to form Merkel cell
      neurite complexes, which are gentle-touch receptors that initiate slowly adapting
      type I responses. The function of Merkel cells within the complex remains debated
      despite decades of research. Numerous anatomical studies demonstrate that Merkel
      cells form synaptic-like contacts with sensory afferent terminals. Moreover,
      recent molecular analysis reveals that Merkel cells express dozens of presynaptic
      molecules that are essential for synaptic vesicle release in neurons. Merkel
      cells also produce a host of neuroactive substances that can act as fast
      excitatory neurotransmitters or neuromodulators. Here, we review the major
      neurotransmitters found in Merkel cells and discuss these findings in relation to
      the potential function of Merkel cells in touch reception.

PMID- 23531000
TI  - Dorsally derived spinal interneurons in locomotor circuits.
AB  - During neuronal circuit formation, axons are guided to their targets by the help
      of axon guidance molecules, which are required for establishing functional
      circuits. A promising system to dissect the development and functionalities of
      neuronal circuitry is the spinal cord central pattern generator (CPG) for
      locomotion, which converts a tonic supraspinal drive to rhythmic and coordinated
      movements. Here we describe concepts arising from genetic studies of the
      locomotor network with a focus on the position and roles of commissural
      interneurons. In particular, this involves studies of several families of axon
      guidance molecules relevant for midline crossing, the Eph/ephrins and Netrin/DCC.
      Effects on developing commissural interneurons in mice with aberrant midline axon
      guidance capabilities suggest that, in addition to ventral populations, dorsal
      commissural interneurons also play a role in coordinating locomotor circuitry.
      Recent findings implicate the novel dI6 interneuron marker Dmrt3 in this role.
      Strikingly, mutations in Dmrt3 result in divergent gait patterns in both mice and
      horses.

PMID- 23530999
TI  - Principles of interneuron development learned from Renshaw cells and the
      motoneuron recurrent inhibitory circuit.
AB  - Renshaw cells provide a convenient model to study spinal circuit development
      during the emergence of motor behaviors with the goal of capturing principles of
      interneuron specification and circuit construction. This work is facilitated by a
      long history of research that generated essential knowledge about the
      characteristics that define Renshaw cells and the recurrent inhibitory circuit
      they form with motoneurons. In this review, we summarize recent data on the
      specification of Renshaw cells and their connections. A major insight from these
      studies is that the basic Renshaw cell phenotype is specified before circuit
      assembly, a result of their early neurogenesis and migration. Connectivity is
      later added, constrained by their placement in the spinal cord. Finally,
      different rates of synapse proliferation alter the relative weights of different
      inputs on postnatal Renshaw cells. Based on this work some general principles on
      the integration of spinal interneurons in developing motor circuits are derived.

PMID- 23531001
TI  - Neuronal correlates of the dominant role of GABAergic transmission in the
      developing mouse locomotor circuitry.
AB  - GABA and glycine are the primary fast inhibitory neurotransmitters in the
      mammalian spinal cord, but they differ in their regulatory functions, balancing
      neuronal excitation in the locomotor circuitry in the mammalian spinal cord. This
      review focuses on the unique role of GABAergic transmission during the assembly
      of the locomotor circuitry, from early embryonic stages when GABA(A) receptor
      activated membrane depolarizations increase network excitation, to the period of
      early postnatal development, when GABAergic inhibition plays a primary role in
      coordinating the patterns of locomotor-like motor activity. To gain insight into
      the mechanisms that underlie the dominant contribution of GABAergic transmission
      to network activity during that period, we examined the morphological and
      electrophysiological properties of a subpopulation of GABAergic commissural
      interneurons that fit well with their putative function as integrated components
      of the rhythm-coordinating networks in the mouse spinal cord.

PMID- 23531002
TI  - GluA1 promotes the activity-dependent development of motor circuitry in the
      developing segmental spinal cord.
AB  - The neuronal dendritic tree is a key determinant of how neurons receive, compute,
      and transmit information. During early postnatal life, synaptic activity promotes
      dendrite elaboration. Spinal motor neurons utilize GluA1-containing AMPA (2-amino
      3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid) receptors (AMPA-R) to
      control this process. This form of developmental dendrite growth can occur
      independently of N-methyl-d-aspartate receptors (NMDA-R). This review focuses on
      the mechanism by which the GluA1 subunit of AMPA-R transforms synaptic activity
      into dendrite growth, and describes the essential role of the GluA1 binding
      partner SAP97 (synapse-associated protein of 97 kDa molecular weight) in this
      process. This work defines a new mechanism of activity-dependent development,
      which might be harnessed to stimulate the recovery of function following insult
      to the central nervous system.

PMID- 23531003
TI  - Optical imaging of the spontaneous depolarization wave in the mouse embryo:
      origins and pharmacological nature.
AB  - Spontaneous embryonic movements, called embryonic motility, are produced by
      correlated spontaneous activity in the cranial and spinal nerves, which is driven
      by brainstem and spinal networks. Using optical imaging with a voltage-sensitive
      dye, we revealed previously in the chick and rat embryos that this correlated
      activity is a widely propagating wave of neural depolarization, which we termed
      the depolarization wave. One important consideration is whether a depolarization
      wave with similar characteristics occurs in other species, especially in
      different mammals. Here, we provide evidence for the existence of the
      depolarization wave in the mouse embryo by summarizing spatiotemporal
      characteristics and pharmacological natures of the widely propagating wave
      activity. The findings show that a synchronized wave with common characteristics
      is expressed in different species, suggesting its fundamental roles in neural
      development.

PMID- 23531004
TI  - Imaging spinal neuron ensembles active during locomotion with genetically encoded
      calcium indicators.
AB  - Advances in molecular-genetic tools for labeling neuronal subtypes, and the
      emerging development of robust genetic probes for neural activity, are likely to
      revolutionize our understanding of the functional organization of neural
      circuits. In principle, these tools should be able to detect activity at cellular
      resolution for large ensembles of identified neuron types as they participate in
      specific behaviors. This report describes the use of genetically encoded calcium
      indicators (GECIs), combined with two-photon microscopy, to characterize V1
      interneurons, known to be critical for setting the duration of the step cycle.
      All V1 interneurons arise from a common precursor population and express
      engrailed-1 (En1). Our data show that although neighboring interneurons that
      arise from the same developmental lineage and share many features, such as
      projection patterns and neurotransmitter profiles, they are not irrevocably
      committed to having the same pattern of activity.

PMID- 23531005
TI  - Glutamatergic reticulospinal neurons in the mouse: developmental origins, axon
      projections, and functional connectivity.
AB  - Subcortical descending glutamatergic neurons, such as reticulospinal (RS)
      neurons, play decisive roles in the initiation and control of many motor
      behaviors in mammals. However, little is known about the mechanisms used by RS
      neurons to control spinal motor networks because most of the neuronal elements
      involved have not been identified and characterized. In this review, we compare,
      in the embryonic mouse, the timing of developmental events that lead to the
      formation of synaptic connections between RS and spinal cord neurons. We then
      summarize our recent research in the postnatal mouse on the organization of
      synaptic connections between RS neurons and lumbar axial motoneurons (MNs),
      hindlimb MNs, and commissural interneurons. Finally, we give a brief account of
      some of the most recent studies on the intrinsic capabilities for plasticity of
      the mammalian RS system. The present review should give an updated insight into
      how functional specificity in RS motor networks emerges.

PMID- 23531006
TI  - Pre- and postsynaptic inhibitory control in the spinal cord dorsal horn.
AB  - Sensory information transmitted to the spinal cord dorsal horn is modulated by a
      complex network of excitatory and inhibitory interneurons. The two main
      inhibitory transmitters, GABA and glycine, control the flow of sensory
      information mainly by regulating the excitability of dorsal horn neurons. A
      presynaptic action of GABA has also been proposed as an important modulatory
      mechanism of transmitter release from sensory primary afferent terminals. By
      inhibiting the release of glutamate from primary afferent terminals, activation
      of presynaptic GABA receptors could play an important role in nociceptive and
      tactile sensory coding, while changes in their expression or function could be
      involved in pathological pain conditions, such as allodynia.

PMID- 23531007
TI  - Activity-dependent development of tactile and nociceptive spinal cord circuits.
AB  - Developing brain circuits are shaped by postnatal sensory experience, but little
      is known about this process at the level of the spinal cord. Here we review the
      mechanisms by which cutaneous sensory input drives the maturation of spinal
      sensory circuits. Newborn animals are highly sensitive to tactile input and
      dorsal horn circuits are dominated by low threshold A fiber inputs. We show that
      this arises from the absence of the functional, targeted glycinergic inhibition
      of tactile activity that emerges only in the second week of life. Selective block
      of afferent C fibers in postnatal week 2 delays the maturation of glycinergic
      inhibition and maintains dorsal horn circuits in a neonatal state. We propose
      that in the newborn strong tactile A fiber input facilitates activity-dependent
      synaptic strengthening in the dorsal horn, but that this ends with the arrival of
      nociceptive C fiber spinal input that drives the maturation of targeted
      glycinergic inhibition.

PMID- 23531008
TI  - Force-sensitive afferents recruited during stance encode sensory depression in
      the contralateral swinging limb during locomotion.
AB  - Afferent feedback alters muscle activity during locomotion and must be tightly
      controlled. As primary afferent depolarization-induced presynaptic inhibition
      (PAD-PSI) regulates afferent signaling, we investigated hindlimb PAD-PSI during
      locomotion in an in vitro rat spinal cord-hindlimb preparation. We compared the
      relation of PAD-PSI, measured as dorsal root potentials (DRPs), to observed
      ipsilateral and contralateral limb endpoint forces. Afferents activated during
      stance-phase force strongly and proportionately influenced DRP magnitude in the
      swinging limb. Responses increased with locomotor frequency. Electrical
      stimulation of contralateral afferents also preferentially evoked DRPs in the
      opposite limb during swing (flexion). Nerve lesioning, in conjunction with
      kinematic results, support a prominent contribution from toe Golgi tendon organ
      afferents. Thus, force-dependent afferent feedback during stance binds interlimb
      sensorimotor state to a proportional PAD-PSI in the swinging limb, presumably to
      optimize interlimb coordination. These results complement known actions of
      ipsilateral afferents on PAD-PSI during locomotion.

PMID- 23531010
TI  - A dual spinal cord lesion paradigm to study spinal locomotor plasticity in the
      cat.
AB  - After a complete spinal cord injury (SCI) at the lowest thoracic level (T13),
      adult cats trained to walk on a treadmill can recover hindlimb locomotion within
      2-3 weeks, resulting from the activity of a spinal circuitry termed the central
      pattern generator (CPG). The role of this spinal circuitry in the recovery of
      locomotion after partial SCIs, when part of descending pathways can still access
      the CPG, is not yet fully understood. Using a dual spinal lesion paradigm (first
      hemisection at T10 followed three weeks after by a complete spinalization at
      T13), we showed that major changes occurred in this locomotor spinal circuitry.
      These plastic changes at the spinal cord level could participate in the recovery
      of locomotion after partial SCI. This short review describes the main findings of
      this paradigm in adult cats.

PMID- 23531011
TI  - The effects of endocannabinoid signaling on network activity in developing and
      motor circuits.
AB  - Endocannabinoid signaling typically mediates a form of synaptic plasticity in
      which a postsynaptic cell acts retrogradely to reduce vesicle release from
      presynaptic terminals impinging on that cell. In the embryonic spinal cord,
      endocannabinoids inhibit spontaneously released glutamatergic vesicles in both a
      brief and ongoing tonic manner. Together these endocannabinoid-mediated forms of
      synaptic regulation appear to play an important role in regulating the frequency
      of a form of spontaneous network activity (SNA) that is expressed in the
      embryonic spinal cord. Because of the importance of SNA to the maturation of the
      developing network, fetal exposure to drugs that influence endocannabinoid
      signaling may have profound effects on spinal maturation. In this review,
      endocannabinoid signaling in the embryonic spinal cord is described and compared
      to signaling in the mature lamprey spinal cord as well as in the developing
      hippocampal network, which expresses a form of SNA.

PMID- 23531009
TI  - Motor primitives and synergies in the spinal cord and after injury--the current
      state of play.
AB  - Modular pattern generator elements, also known as burst synergies or motor
      primitives, have become a useful and important way of describing motor behavior,
      albeit controversial. It is suggested that these synergy elements may constitute
      part of the pattern-shaping layers of a McCrea/Rybak two-layer pattern generator,
      as well as being used in other ways in the spinal cord. The data supporting
      modular synergies range across species including humans and encompass motor
      pattern analyses and neural recordings. Recently, synergy persistence and changes
      following clinical trauma have been presented. These new data underscore the
      importance of understanding the modular structure of motor behaviors and the
      underlying circuitry to best provide principled therapies and to understand
      phenomena reported in the clinic. We discuss the evidence and different
      viewpoints on modularity, the neural underpinnings identified thus far, and
      possible critical issues for the future of this area.

PMID- 23531012
TI  - Hypoxia-induced phrenic long-term facilitation: emergent properties.
AB  - As in other neural systems, plasticity is a hallmark of the neural system
      controlling breathing. One spinal mechanism of respiratory plasticity is phrenic
      long-term facilitation (pLTF) following acute intermittent hypoxia. Although
      cellular mechanisms giving rise to pLTF occur within the phrenic motor nucleus,
      different signaling cascades elicit pLTF under different conditions. These
      cascades, referred to as Q and S pathways to phrenic motor facilitation (pMF),
      interact via cross-talk inhibition. Whereas the Q pathway dominates pLTF after
      mild to moderate hypoxic episodes, the S pathway dominates after severe hypoxic
      episodes. The biological significance of multiple pathways to pMF is unknown.
      This review will discuss the possibility that interactions between pathways
      confer emergent properties to pLTF, including pattern sensitivity and
      metaplasticity. Understanding these mechanisms and their interactions may enable
      us to optimize intermittent hypoxia-induced plasticity as a treatment for
      patients that suffer from ventilatory impairment or other motor deficits.

PMID- 23531013
TI  - Axon regeneration and exercise-dependent plasticity after spinal cord injury.
AB  - Current dogma states that meaningful recovery of function after spinal cord
      injury (SCI) will likely require a combination of therapeutic interventions
      comprised of regenerative/neuroprotective transplants, addition of neurotrophic
      factors, elimination of inhibitory molecules, functional sensorimotor training,
      and/or stimulation of paralyzed muscles or spinal circuits. We routinely use (1)
      peripheral nerve grafts to support and direct axonal regeneration across an
      incomplete cervical or complete thoracic transection injury, (2) matrix
      modulation with chondroitinase (ChABC) to facilitate axonal extension beyond the
      distal graft-spinal cord interface, and (3) exercise, such as forced wheel
      walking, bicycling, or step training on a treadmill. We and others have
      demonstrated an increase in spinal cord levels of endogenous neurotrophic factors
      with exercise, which may be useful in facilitating elongation and/or synaptic
      activity of regenerating axons and plasticity of spinal neurons below the level
      of injury.

PMID- 23531015
TI  - Multidimensional supersymmetric quantum mechanics: spurious states for the tensor
      sector two Hamiltonian.
AB  - We show that there exist spurious states for the sector two tensor Hamiltonian in
      multidimensional supersymmetric quantum mechanics. For one-dimensional
      supersymmetric quantum mechanics on an infinite domain, the sector one and two
      Hamiltonians have identical spectra with the exception of the ground state of the
      sector one. For tensorial multidimensional supersymmetric quantum mechanics,
      there exist normalizable spurious states for the sector two Hamiltonian with
      energy equal to the ground state energy of the sector one. These spurious states
      are annihilated by the adjoint charge operator, and hence, they do not correspond
      to physical states for the original Hamiltonian. The Hermitian property of the
      sector two Hamiltonian implies the orthogonality between spurious and physical
      states. In addition, we develop a method for construction of a specific form of
      the spurious states for any quantum system and also generate several spurious
      states for a two-dimensional anharmonic oscillator system and for the hydrogen
      atom.

PMID- 23531014
TI  - Accelerating locomotor recovery after incomplete spinal injury.
AB  - A traumatic spinal injury can destroy cells, irreparably damage axons, and
      trigger a cascade of biochemical responses that increase the extent of injury.
      Although damaged central nervous system axons do not regrow well naturally, the
      distributed nature of the nervous system and its capacity to adapt provide
      opportunities for recovery of function. It is apparent that activity-dependent
      plasticity plays a role in this recovery and that the endogenous response to
      injury heightens the capacity for recovery for at least several weeks postinjury.
      To restore locomotor function, researchers have investigated the use of treadmill
      based training, robots, and electrical stimulation to tap into adaptive activity
      dependent processes. The current challenge is to maximize the degree of
      functional recovery. This manuscript reviews the endogenous neural system
      response to injury, and reviews data and presents novel analyses of these from a
      rat model of contusion injury that demonstrates how a targeted intervention can
      accelerate recovery, presumably by engaging processes that underlie activity
      dependent plasticity.

PMID- 23531016
TI  - Development of a green binder system for paper products.
AB  - BACKGROUND: It is important for industries to find green chemistries for
      manufacturing their products that have utility, are cost-effective and that
      protect the environment. The paper industry is no exception. Renewable resources
      derived from plant components could be an excellent substitute for the chemicals
      that are currently used as paper binders. Air laid pressed paper products that
      are typically used in wet wipes must be bound together so they can resist
      mechanical tearing during storage and use. The binders must be strong but cost
      effective. Although chemical binders are approved by the Environmental Protection
      Agency, the public is demanding products with lower carbon footprints and that
      are derived from renewable sources. RESULTS: In this project, carbohydrates,
      proteins and phenolic compounds were applied to air laid, pressed paper products
      in order to identify potential renewable green binders that are as strong as the
      current commercial binders, while being organic and renewable. Each potential
      green binder was applied to several filter paper strips and tested for strength
      in the direction perpendicular to the cellulose fibril orientation. Out of the
      twenty binders surveyed, soy protein, gelatin, zein protein, pectin and Salix
      lignin provided comparable strength results to a currently employed chemical
      binder. CONCLUSIONS: These organic and renewable binders can be purchased in
      large quantities at low cost, require minimal reaction time and do not form
      viscous solutions that would clog sprayers, characteristics that make them
      attractive to the non-woven paper industry. As with any new process, a large
      scale trial must be conducted along with an economic analysis of the procedure.
      However, because multiple examples of "green" binders were found that showed
      strong cross-linking activity, a candidate for commercial application will likely
      be found.

PMID- 23531017
TI  - Management of venous thromboembolism--controversies and the future.
AB  - Despite the availability of comprehensive evidence-based guidelines there are
      difficult and controversial areas in the management of venous thromboembolism.
      Institutions and even countries disagree on the importance of calf vein
      thrombosis, with some rigorously detecting and treating it and others
      deliberately not looking for it. The need to treat proximal deep vein thrombosis
      and pulmonary embolism is accepted but which patients with an unprovoked first
      event should have long-term anticoagulation has become a difficult clinical
      decision. We are uncertain how to reduce the incidence of post-thrombotic
      syndrome seen in a substantial number of patients. How hard to look for an
      undiagnosed underlying cancer has become a contentious issue particularly in the
      United Kingdom following the recent publication of a guideline from the National
      Institute for Health and Clinical Excellence. Whilst we are wrestling with these
      dilemmas we are entering an era of new anticoagulants and have to solve the
      logistical problems of introducing them into clinical practice despite cost
      pressures. These issues will be explored in this review.

PMID- 23531018
TI  - Edge-effect interactions in fragmented and patchy landscapes.
AB  - Ecological edges are increasingly recognized as drivers of landscape patterns and
      ecosystem processes. In fragmented and patchy landscapes (e.g., a fragmented
      forest or a savanna with scattered termite mounds), edges can become so numerous
      that their effects pervade the entire landscape. Results of recent studies in
      such landscapes show that edge effects can be altered by the presence or
      proximity of other nearby edges. We considered the theoretical significance of
      edge-effect interactions, illustrated various landscape configurations that
      support them and reviewed existing research on this topic. Results of studies
      from a variety of locations and ecosystem types show that edge-effect
      interactions can have significant consequences for ecosystems and conservation,
      including higher tree mortality rates in tropical rainforest fragments, reduced
      bird densities in grassland fragments, and bush encroachment and reduced wildlife
      densities in a tropical savanna. To clarify this underappreciated concept and
      synthesize existing work, we devised a conceptual framework for edge-effect
      interactions. We first worked to reduce terminological confusion by clarifying
      differences among terms such as edge intersection and edge interaction. For cases
      in which nearby edge effects interact, we proposed three possible forms of
      interaction: strengthening (presence of a second edge causes stronger edge
      effects), weakening (presence of a second edge causes weaker edge effects), and
      emergent (edge effects change completely in the presence of a second edge). By
      clarifying terms and concepts, this framework enables more precise descriptions
      of edge-effect interactions and facilitates comparisons of results among
      disparate study systems and response variables. A better understanding of edge
      effect interactions will pave the way for more appropriate modeling,
      conservation, and management in complex landscapes.

PMID- 23531019
TI  - The INDDEP study: inpatient and day hospital treatment for depression - symptom
      course and predictors of change.
AB  - BACKGROUND: Depression can be treated in an outpatient, inpatient or day hospital
      setting. In the German health care system, episodes of inpatient or day hospital
      treatment are common, but there is a lack of studies evaluating effectiveness in
      routine care and subgroups of patients with a good or insufficient treatment
      response. Our study aims at identifying prognostic and prescriptive outcome
      predictors as well as comparative effectiveness in psychosomatic inpatient and
      day hospital treatment in depression. METHODS/DESIGN: In a naturalistic study,
      300 consecutive inpatient and 300 day hospital treatment episodes in seven
      psychosomatic hospitals in Germany will be included. Patients are assessed at
      four time points of measurement (admission, discharge, 3-months follow-up, 12
      months follow-up) including a broad range of variables (self-report and expert
      ratings). First, the whole sample will be analysed to identify prognostic and
      prescriptive predictors of outcome (primary outcome criterion: Quick Inventory of
      Depressive Symptoms QIDS-total score, expert rating). Secondly, for a comparison
      of inpatient and day hospital treatment, samples will be matched according to
      known predictors of outcome. DISCUSSION: Naturalistic studies with good external
      validity are needed to assess treatment outcome in depression in routine care and
      to identify subgroups of patients with different therapeutic needs. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN20317064.

PMID- 23531020
TI  - Can carbon monoxide prevent infection-mediated preterm birth in a mouse model?
AB  - PROBLEM: Preterm birth is frequently caused by intrauterine infection and
      inflammation. Recent studies have demonstrated that carbon monoxide (CO), which
      is produced endogenously, has potent anti-inflammatory properties. Whether or not
      CO can prevent infection-mediated preterm birth is unknown. METHODS: Mice were
      assigned to one of four groups: sham infection, sham infection + CO, infection,
      or infection + CO. Infections were established by intra-uterine injection of
      Escherichia coli on day 14 of pregnancy. Animals received daily i.p. injections
      of 1 mL CO-saturated lactated ringers solution (LRS) or LRS alone beginning on
      the morning of surgery. Gestational age at delivery and litter characteristics
      was noted. In second experiment, animals were sacrificed 24 hrs post-surgery and
      tissues were harvested for cytokine analyses. RESULTS: Escherichia coli
      intrauterine infection increased the number of animals delivering preterm. This
      effect was significantly ameliorated by CO-LRS. CO-treatment also increased
      litter size and weights of the surviving offspring. Cytokines in the amniotic
      fluid and the placenta were increased by E. coli exposure, but CO had no
      detectible effect on E. coli-stimulated cytokine production. No effects of CO
      were detected in sham-infected animals. CONCLUSION: Supplemental CO improves
      pregnancy outcome after intrauterine infection and may function at a point
      downstream of, or through pathways independent of, induction of proinflammatory
      cytokines.

PMID- 23531021
TI  - Elemental and isotopic fingerprint of Argentinean wheat. Matching soil, water,
      and crop composition to differentiate provenance.
AB  - The aim of this study was to investigate if elemental and isotopic signatures of
      Argentinean wheat can be used to develop a reliable fingerprint to assess its
      geographical provenance. For this pilot study we used wheat cultivated at three
      different regions (Buenos Aires, Cordoba, and Entre Rios), together with matching
      soil and water. Elemental composition was determined by ICP-MS. delta(13)C and
      delta(15)N were measured by isotopic ratio mass spectrometry, while (87)Sr/(86)Sr
      ratio was determined using thermal ionization mass spectrometry. Wheat samples
      from three sampling sites were differentiated by the combination of 11 key
      variables (K/Rb, Ca/Sr, Ba, (87)Sr/(86)Sr, Co, Mo, Zn, Mn, Eu, delta(13)C, and
      Na), demonstrating differences among the three studied regions. The application
      of generalized Procrustes analysis showed 99.2% consensus between cultivation
      soil, irrigation water, and wheat samples, in addition to clear differences
      between studied areas. Furthermore, canonical correlation analysis showed
      significant correlation between the elemental and isotopic profiles of wheat and
      those corresponding to both soil and water (r(2) = 0.97, p < 0.001 and r(2) =
      0.96, p < 0.001, respectively). To our knowledge, this is the first report
      demonstrating the correspondence between soil, water, and wheat samples using
      different statistical methods, showing that wheat elemental and isotopic
      compositions are mainly related to soil and irrigation water characteristics of
      the site of growth. 

PMID- 23531022
TI  - Consultation etiquette in palliative care #266.

PMID- 23531023
TI  - Assessing patient care in palliative care using the healthcare matrix.
AB  - The healthcare matrix is a novel assessment tool that facilitates systematic
      examination of patient cases using criteria established by the Accreditation
      Council for Graduate Medical Education and the Institute of Medicine. It is
      particularly useful for analyzing complex cases, although its use in the
      palliative care setting has not been documented. We describe here the use of the
      healthcare matrix to examine the healthcare encounters of a 63 year-old patient
      with advanced cancer. The healthcare matrix helped us to dissect the physical,
      psychosocial, logistical, professional, and ethical aspects of care, and to
      highlight multiple opportunities for quality improvement. In addition to the case
      example we will be discussing the advantages and disadvantages for using the
      healthcare matrix and its potential utility in palliative care.

PMID- 23531024
TI  - Writing the consultation note #267.

PMID- 23531025
TI  - Dyspnea can be, and should be, effectively palliated with opioids.

PMID- 23531026
TI  - The effect of expressive art on fatigue in palliative medicine fellows.

PMID- 23531027
TI  - The beauty of death and "I don't know".

PMID- 23531028
TI  - Breast lesions with intractable pain in end-stage renal disease: calciphylaxis
      with chronic hypotensive dermatopathy related watershed breast lesions.
AB  - BACKGROUND: There are very few reports about end-stage renal disease (ESRD)
      patients with breast pains in the medical literature, posing a difficulty to
      understand their pathophysiology. CASE PRESENTATION: A 47-year-old African
      American female patient with ESRD on hemodialysis presented to the pain clinic
      with new-onset black maculopapular skin lesions on her breasts. These lesions
      started out as dark spots and then became necrosed, exposing the underlying
      tissue. The painful and tender lesions were located in a circumferential pattern
      around the bases of both breasts. She had stopped using breast supporting
      undergarments secondary to allodynia-hyperalgesia eliciting from necrotizing skin
      tissues. Her recent skin biopsy was inconclusive about ruling in or out the
      possibility of calciphylaxis. However, her past mammograms had showed calcium
      deposits in her breasts. Her other past medical history was significant for
      chronic hypotension with recently diagnosed legal blindness bilaterally. Her home
      medications included midodrine. The systolic blood pressures in either arm were
      consistently recorded in high 60s to low 70s during the interdialytic periods.
      She had multiple emergency room admissions secondary to persistent chronic
      hypotension; however the underlying pathophysiology for intractable but
      asymptomatic hypotension remained obscure. Over the course of the next 11 months
      her nonhealing breast lesions progressed and became infected. She developed
      septic shock due to infected lesions. Per her do-not-resuscitate requests, she
      died peacefully while under inhospital hospice care. CONCLUSION: Morbidity
      mortality with calciphylaxis and chronic hypotension related tissue changes is
      high, and the breast lesions in ESRD patients require aggressive treatment for
      underlying inadequate oxygen delivery to these peripheral tissues.

PMID- 23531029
TI  - Treatment of frontal fibrosing alopecia and lichen planopilaris: a systematic
      review.
AB  - Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia
      with characteristic clinical pattern of progressive frontotemporal hairline
      recession, perifollicular erythema and hyperkeratosis and symptoms of itch and
      burning, occurring mainly in post-menopausal women. FFA is considered a subtype
      of lichen planopilaris (LPP), based on their identical histopathology. Currently,
      no evidence-based treatment is available for FFA. Our aim was to determine the
      effectiveness of available treatment options for FFA, and to identify promising
      treatment options for future studies. For this, literature search was conducted
      to find all primary studies on the treatment of FFA and LPP. From the primary
      studies, data were subtracted and analysed. No randomized controlled trials were
      found, and one controlled trial. Treatment of 114 patients is described in the
      literature. They received 10 different regimes, of which oral 5-alpha-reductase
      inhibitors were provided most often, resulting in good clinical response in 45%
      of them. Hydroxychloroquine resulted in good clinical response in 30% of the 29
      treated patients. Topical corticosteroid preparations are ineffective in FFA. The
      remaining treatments were all reported in less than 10 patients. For the
      treatment of LPP, topical corticosteroid preparations are the first line of
      treatment, followed by oral cyclosporine and systemic corticosteroids, although
      they are characterized by a high relapse rate. Summarizing, there is currently no
      effective treatment of FFA, the most effective being oral 5-alpha-reductase
      inhibitors that possibly affect the accompanying androgenetic alopecia. We argue
      that oral cyclosporine A might be a good candidate for future studies on the
      treatment of FFA. 

PMID- 23531031
TI  - Histone deacetylase inhibition affects sodium iodide symporter expression and
      induces 131I cytotoxicity in anaplastic thyroid cancer cells.
AB  - BACKGROUND: Anaplastic thyroid cancers (ATCs) represent only 1%-2% of all thyroid
      tumors, but they account for up to 50% of the mortality. Treatment of
      differentiated thyroid carcinomas is well standardized and the use of radioiodine
      represents an essential step; in contrast, there is no standardized therapeutic
      approach for anaplastic tumors and their prognosis is poor. The resistance of ATC
      to radioiodine treatment is principally due to the absence of expression of the
      sodium iodide symporter (NIS), mainly due to epigenetic silencing. The
      acetylation status of histones is involved in the epigenetic control of gene
      expression and is usually disrupted in advanced thyroid cancer. Histone
      deacetylase inhibitors have been demonstrated as potent anticancer drugs with
      several different effects on cell viability and differentiation. METHODS:
      Stabilized ATC cell lines (BHT-101 and CAL-62) and primary cultures from patients
      who underwent thyroidectomy for ATC were treated with the histone deacetylase
      inhibitor LBH589. After treatment, we evaluated the expression and function of
      NIS. Gene expression was evaluated by real-time polymerase chain reaction (RT
      PCR), NIS promoter activity was determined with a luciferase reporter assay, and
      protein expression was assessed through immunofluorescence. We tested the protein
      function by (125)I uptake and efflux experiments; finally the cytotoxic effect of
      (131)I was determined with a clonogenic assay. RESULTS: Our results demonstrate
      that treatment with LBH589 leads to NIS RNA expression as shown by RT-PCR and
      luciferase assay, and to protein expression as determined by immunofluorescence
      in vitro and by immunohistochemistry in xenograft tumors. Moreover, (125)I uptake
      and efflux experiments show the correct protein function and iodine retention,
      which translate into cytotoxicity effects, as demonstrated by a clonogenic assay
      with (131)I. CONCLUSIONS: This study supplies a new potential strategy for the
      treatment of ATC by modifying gene expression with the aim of inducing
      responsiveness towards radioiodine therapy.

PMID- 23531032
TI  - Prediction of efficacy to pegylated interferon-alpha-2b plus ribavirin in
      patients with genotype 2 hepatitis C virus using viral response within 2 weeks.
AB  - AIM: Rapid virological response (RVR), defined as serum hepatitis C virus (HCV)
      RNA negativity at 4 weeks, is the most useful predictor of sustained virological
      response (SVR) to standard pegylated interferon (PEG IFN) plus ribavirin therapy
      for patients infected with genotype 2 HCV. The aim of the present study was to
      predict SVR using viral response within 2 weeks of therapy initiation. METHODS:
      Of 64 HCV genotype 2 patients with a high viral load treated with standard PEG
      IFN-alpha-2b plus weight-based ribavirin for 24 weeks, 58 patients whose
      adherence was more than 67% were analyzed. RNA and core antigen levels were
      measured at four time points: the day of therapy initiation, the following day,
      and at 1 and 2 weeks. RESULTS: SVR was achieved in 73% (47/64) of patients.
      Univariate analysis of SVR contributing factors showed significant differences
      with age, bodyweight, white blood cell count, platelet count, fibrosis marker
      levels, baseline core antigen level and viral response. The area under the
      receiver-operator curve (AUC) of the core antigen level at 1 week (AUC, 0.940)
      was the highest among the significant SVR predicting factors. Setting 100 fmol/L
      as the cut-off value for core antigen level at 1 week, the sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      for predicting SVR were 100%, 86%, 96%, 100% and 97%, respectively, and for
      predicting RVR were 66%, 93%, 97%, 46% and 72%, respectively. CONCLUSION: The HCV
      core antigen level at 1 week after therapy initiation is the most useful
      predictor for SVR.

PMID- 23531033
TI  - Pharmacokinetics of tobramycin following intravenous, intramuscular, and intra
      articular administration in healthy horses.
AB  - The objectives of this study were to examine the pharmacokinetics of tobramycin
      in the horse following intravenous (IV), intramuscular (IM), and intra-articular
      (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with
      concurrent IA administration (IV+IA) in a randomized 3-way crossover design. A
      washout period of at least 7 days was allotted between experiments. After IV
      administration, the volume of distribution, clearance, and half-life were 0.18 +/
      0.04 L/kg, 1.18 +/- 0.32 mL.kg/min, and 4.61 +/- 1.10 h, respectively.
      Concurrent IA administration could not be demonstrated to influence IV
      pharmacokinetics. The mean maximum plasma concentration (Cmax ) after IM
      administration was 18.24 +/- 9.23 MUg/mL at 1.0 h (range 1.0-2.0 h), with a mean
      bioavailability of 81.22 +/- 44.05%. Intramuscular administration was well
      tolerated, despite the high volume of drug administered (50 mL per 500 kg horse).
      Trough concentrations at 24 h were below 2 MUg/mL in all horses after all routes
      of administration. Specifically, trough concentrations at 24 h were 0.04 +/- 0.01
      MUg/mL for the IV route, 0.04 +/- 0.02 MUg/mL for the IV/IA route, and 0.02 +/-
      0.02 for the IM route. An additional six mares received IA administration of 240
      mg tobramycin. Synovial fluid concentrations were 3056.47 +/- 1310.89 MUg/mL at
      30 min after administration, and they persisted for up to 48 h with
      concentrations of 14.80 +/- 7.47 MUg/mL. Tobramycin IA resulted in a mild
      chemical synovitis as evidenced by an increase in synovial fluid cell count and
      total protein, but appeared to be safe for administration. Monte Carlo
      simulations suggest that tobramycin would be effective against bacteria with a
      minimum inhibitory concentration (MIC) of 2 MUg/mL for IV administration and 1
      MUg/mL for IM administration based on Cmax :MIC of 10. 

PMID- 23531035
TI  - The path of least resistance: enhancing the effectiveness of BRAF inhibitors.

PMID- 23531034
TI  - Microbiological characterization of Streptococcus pneumoniae and non-typeable
      Haemophilus influenzae isolates as primary causes of acute otitis media in
      Bulgarian children before the introduction of conjugate vaccines.
AB  - BACKGROUND: Pneumococcal and Haemophilus influenzae type b (Hib) vaccines were
      introduced in our national immunisation program in April 2010. The aims of this
      retrospective, laboratory-based study were to determine the serotypes and
      antibiotic resistance of Streptococcus pneumoniae and H. influenzae isolates from
      middle ear fluid (MEF) collected before the introduction of immunization.
      METHODS: S. pneumoniae (n = 128) and H. influenzae (n = 40) strains isolated from
      MEF of children with AOM between 1994 and 2011 were studied. MICs were determined
      by a microdilution assay. Serotyping of S. pneumoniae was done by Quellung method
      and PCR capsular typing was used for H. influenzae. Macrolide resistance genes
      were detected by PCR for erythromycin resistant S. pneumoniae (ERSP). DNA
      sequencing of ftsI gene was performed for ampicillin nonsusceptible H.
      influenzae. RESULTS: The most common serotypes found among children with
      pneumococcal AOM were 19 F (20.3%), 6B (15.6%), and 19A (10.9%). The potential
      coverage rates by the PCV7, PCV10 and PCV13 of children aged < 5 years were
      63.6%, 66.4% and 85.5%, respectively. Reduced susceptibility to oral penicillin
      was seen in 68.1%; resistance to erythromycin was 46.9%. We found erm(B) gene in
      56.7% of the ERSP, mef(E) gene in 25%; 15% harbored both genes erm(B) + mef(E)
      and 3.3% had mutations of L4 ribosomal protein. Of the 40 H. influenzae isolates
      97.5% were nontypeable. Nonsusceptibility to ampicillin occurred in 25%.
      Ampicillin resistance groups were: beta-lactamase-positive ampicillin resistant
      (BLPAR) strains (10%), beta-lactamase-negative ampicillin resistant (BLNAR)
      strains (12.5%) and beta-lactamase-positive amoxicillin-clavulanate resistant
      (BLPACR) strains (2.5%). Among BLNAR and BLPACR most of the isolates (5/6)
      belonged to group II, defined by the Asn526Lys substitution. CONCLUSIONS: The
      levels of antibiotic resistance among S. pneumoniae and H. influenzae causing
      severe AOM in children are high in our settings. The existence of multidrug
      resistant S. pneumoniae serotype 19A is of particular concern. The rate of BLNAR
      and BLPACR strains among H. influenzae isolates was 15%.

PMID- 23531036
TI  - Multidimensional supersymmetric quantum mechanics: a scalar Hamiltonian approach
      to excited states by the imaginary time propagation method.
AB  - Supersymmetric quantum mechanics (SUSY-QM) is shown to provide a novel approach
      to the construction of the initial states for the imaginary time propagation
      method to determine the first and second excited state energies and wave
      functions for a two-dimensional system. In addition, we show that all
      calculations are carried out in sector one and none are performed with the tensor
      sector two Hamiltonian. Through our tensorial approach to multidimensional
      supersymmetric quantum mechanics, we utilize the correspondence between the
      eigenstates of the sector one and two Hamiltonians to construct appropriate
      initial sector one states from sector two states for the imaginary time
      propagation method. The imaginary time version of the time-dependent Schrodinger
      equation is integrated to obtain the first and second excited state energies and
      wave functions using the split operator method for a two-dimensional anharmonic
      oscillator system and a two-dimensional double well potential. The computational
      results indicate that we can obtain the first two excited state energies and wave
      functions even when a quantum system does not exhibit any symmetry. Moreover,
      instead of dealing with the increasing computational complexity resulting from
      computations in the tensor sector two Hamiltonian, this study presents a new
      supersymmetric approach to calculations of accurate excited state energies and
      wave functions by directly using the scalar sector one Hamiltonian.

PMID- 23531037
TI  - Tubular reabsorption and local production of urine hepcidin-25.
AB  - BACKGROUND: Hepcidin is a central regulator of iron metabolism. Serum hepcidin
      levels are increased in patients with renal insufficiency, which may contribute
      to anemia. Urine hepcidin was found to be increased in some patients after
      cardiac surgery, and these patients were less likely to develop acute kidney
      injury. It has been suggested that urine hepcidin may protect by attenuating heme
      mediated injury, but processes involved in urine hepcidin excretion are unknown.
      METHODS: To assess the role of tubular reabsorption we compared fractional
      excretion (FE) of hepcidin-25 with FE of beta2-microglobulin (beta(2)m) in 30
      patients with various degrees of tubular impairment due to chronic renal disease.
      To prove that hepcidin is reabsorbed by the tubules in a megalin-dependent
      manner, we measured urine hepcidin-1 in wild-type and kidney specific megalin
      deficient mice. Lastly, we evaluated FE of hepcidin-25 and beta(2)m in 19
      patients who underwent cardiopulmonary bypass surgery. Hepcidin was measured by a
      mass spectrometry assay (MS), whereas beta(2)m was measured by ELISA. RESULTS: In
      patients with chronic renal disease, FE of hepcidin-25 was strongly correlated
      with FE of beta(2)m (r = 0.93, P <0.01). In megalin-deficient mice, urine
      hepcidin-1 was 7-fold increased compared to wild-type mice (p < 0.01) indicating
      that proximal tubular reabsorption occurs in a megalin- dependent manner.
      Following cardiac surgery, FE of hepcidin-25 increased despite a decline in FE of
      beta(2)m, potentially indicating local production at 12-24 hours. CONCLUSIONS:
      Hepcidin-25 is reabsorbed by the renal tubules and increased urine hepcidin-25
      levels may reflect a reduction in tubular uptake. Uncoupling of FE of hepcidin-25
      and beta(2)m in cardiac surgery patients suggests local production.

PMID- 23531038
TI  - Epidermotropic marginal zone lymphoma simulating mycosis fungoides(?).
AB  - Cutaneous lymphomas can usually be distinguished by architectural features, where
      most atypical lichenoid infiltrates implicate cutaneous T-cell lymphoma (CTCL).
      We report a case of an 80-year-old man who presented with asymptomatic golden
      brown patches and diffuse pink papules on his trunk, buttocks and hips. Biopsies
      revealed a lichenoid infiltrate and areas of epidermotropism. Although the
      overall architectural pattern was compatible with mycosis fungoides, the
      lymphocytes had a more monocytoid and plasmacytoid appearance, and there were
      interspersed mature plasma cells. Immunohistological studies revealed that the
      pleomorphic lymphocytes were predominantly B cells (CD20?+ and CD79a?+) with a
      subpopulation of smaller bland T cells (CD3?+). Moreover, the B-cell
      immunophenotype was compatible with marginal zone differentiation (bcl-2+, bcl-6
      , CD10- and CD5-) and showed a lambda light chain restriction, confirming
      monoclonality. These findings were diagnostic for cutaneous marginal zone B-cell
      lymphoma (MZL) with epidermotropism an entity which has only been reported twice
      in the literature, once in the setting of primary cutaneous disease, and once as
      cutaneous involvement of systemic disease. This case illustrates a rare pattern
      of cutaneous MZL, and underscores the importance of immunophenotypic
      characterization of cutaneous lymphomas in order to prevent the misdiagnosis of a
      CTCL.

PMID- 23531039
TI  - Adhesion and nanomechanics of pili from the probiotic Lactobacillus rhamnosus GG.
AB  - Knowledge of the mechanisms by which bacterial pili adhere to host cells and
      withstand external forces is critical to our understanding of their functional
      roles and offers exciting avenues in biomedicine for controlling the adhesion of
      bacterial pathogens and probiotics. While much progress has been made in the
      nanoscale characterization of pili from Gram-negative bacteria, the adhesive and
      mechanical properties of Gram-positive bacterial pili remain largely unknown.
      Here, we use single-molecule atomic force microscopy to unravel the binding
      mechanism of pili from the probiotic Gram-positive bacterium Lactobacillus
      rhamnosus GG (LGG). First, we show that SpaC, the key adhesion protein of the LGG
      pilus, is a multifunctional adhesin with broad specificity. SpaC forms homophilic
      trans-interactions engaged in bacterial aggregation and specifically binds mucin
      and collagen, two major extracellular components of host epithelial layers.
      Homophilic and heterophilic interactions display similar binding strengths and
      dissociation rates. Next, pulling experiments on living bacteria demonstrate that
      LGG pili exhibit two unique mechanical responses, that is, zipper-like adhesion
      involving multiple SpaC molecules distributed along the pilus length and
      nanospring properties enabling pili to resist high force. These mechanical
      properties may represent a generic mechanism among Gram-positive bacterial pili
      for strengthening adhesion and withstanding shear stresses in the natural
      environment. The single-molecule experiments presented here may help us to design
      molecules capable of promoting or inhibiting bacterial-host interactions.

PMID- 23531040
TI  - Click chemistry for drug development and diverse chemical-biology applications.

PMID- 23531041
TI  - Photobiomodulation preserves behaviour and midbrain dopaminergic cells from MPTP
      toxicity: evidence from two mouse strains.
AB  - BACKGROUND: We have shown previously that near-infrared light (NIr) treatment or
      photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars
      compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) in Balb/c albino mice, a well-known model for
      Parkinson's disease. The present study explores whether NIr treatment offers
      neuroprotection to these cells in C57BL/6 pigmented mice. In addition, we examine
      whether NIr influences behavioural activity in both strains after MPTP treatment.
      We tested for various locomotive parameters in an open-field test, namely
      velocity, high mobility and immobility. RESULTS: Balb/c (albino) and C57BL/6
      (pigmented) mice received injections of MPTP (total of 50 mg/kg) or saline and
      NIr treatments (or not) over 48 hours. After each injection and/or NIr treatment,
      the locomotor activity of the mice was tested. After six days survival, brains
      were processed for TH (tyrosine hydroxylase) immunochemistry and the number of
      TH+ cells in the substantia nigra pars compacta (SNc) was estimated using
      stereology. Results showed higher numbers of TH+ cells in the MPTP-NIr groups of
      both strains, compared to the MPTP groups, with the protection greater in the
      Balb/c mice (30% vs 20%). The behavioural tests revealed strain differences also.
      For Balb/c mice, the MPTP-NIr group showed greater preservation of locomotor
      activity than the MPTP group. Behavioural preservation was less evident in the
      C57BL/6 strain however, with little effect of NIr being recorded in the MPTP
      treated cases of this strain. Finally, there were differences between the two
      strains in terms of NIr penetration across the skin and fur. Our measurements
      indicated that NIr penetration was considerably less in the pigmented C57BL/6,
      compared to the albino Balb/c mice. CONCLUSIONS: In summary, our results revealed
      the neuroprotective benefits of NIr treatment after parkinsonian insult at both
      cellular and behavioural levels and suggest that Balb/c strain, due to greater
      penetration of NIr through skin and fur, provides a clearer model of protection
      than the C57BL/6 strain.

PMID- 23531042
TI  - Effect of spawning on furan fatty acid profile of edible muscle and organ tissues
      from sardine (Sardina pilchardus) and anchovy (Engraulis encrasicolus).
AB  - The total fatty acid compositions, especially the furan fatty acid (F-acids)
      profile, from edible muscle (fillet) and organ tissues (brain, eye, ovaries, and
      testes) of spawning and nonspawning sardine and anchovy were examined. The
      spawning season had no effect on F-acid profiles of the fillet and all organ
      tissues, for both fishes. However, differences among the F-acid fraction of the
      organ tissues were revealed. The F-acid portion was less than 1% of total fatty
      acid in all samples. Five F-acid congeners were detected in the fillet, eye, and
      gonads, while the brain contained only four F-acids. Unlike the F-acids, spawning
      season affected the docosahexaenoic acid (DHA) abundance in fillet and gonads.
      DHA enrichment occurred in fillets and gonads from spawning sardine and anchovy.
      The ratio omega3 PUFA/omega6 PUFA decreases between spawning and nonspawning
      fillets, thus the fillets from spawning fish have higher nutritional value. 

PMID- 23531043
TI  - Enhanced transgene expression in rice following selection controlled by weak
      promoters.
AB  - BACKGROUND: Techniques that enable high levels of transgene expression in plants
      are attractive for the commercial production of plant-made recombinant
      pharmaceutical proteins or other gene transfer related strategies. The
      conventional way to increase the yield of desired transgenic products is to use
      strong promoters to control the expression of the transgene. Although many such
      promoters have been identified and characterized, the increase obtainable from a
      single promoter is ultimately limited to a certain extent. RESULTS: In this
      study, we report a method to magnify the effect of a single promoter by using a
      weak promoter-based selection system in transgenic rice. tCUP1, a fragment
      derived from the tobacco cryptic promoter (tCUP), was tested for its activity in
      rice by fusion to both a beta-glucuronidase (GUS) reporter and a hygromycin
      phosphotransferase (HPT) selectable marker. The tCUP1 promoter allowed the
      recovery of transformed rice plants and conferred tissue specific expression of
      the GUS reporter, but was much weaker than the CaMV 35S promoter in driving a
      selectable marker for growth of resistant calli. However, in the resistant calli
      and regenerated transgenic plants selected by the use of tCUP1, the constitutive
      expression of green fluorescent protein (GFP) was dramatically increased as a
      result of the additive effect of multiple T-DNA insertions. The correlation
      between attenuated selection by a weak promoter and elevation of copy number and
      foreign gene expression was confirmed by using another relatively weak promoter
      from nopaline synthase (Nos). CONCLUSIONS: The use of weak promoter derived
      selectable markers leads to a high T-DNA copy number and then greatly increases
      the expression of the foreign gene. The method described here provides an
      effective approach to robustly enhance the expression of heterogenous transgenes
      through copy number manipulation in rice.

PMID- 23531044
TI  - Interfacial dilatational viscoelasticity of human meibomian lipid films.
AB  - PURPOSE/AIM: The meibomian lipid layer is able to withstand the enormous stresses
      and deformations that occur during blinking due to the combination of its elastic
      and viscous properties. The purpose of this study was to measure the dilatational
      viscoelasticity of in vitro meibomian lipid films and compare how these
      properties differ between room temperature and physiological temperatures.
      Viscoelasticity was also compared with meibomian lipid films seeded with
      cholesterol or beta-carotene (the levels of these lipid species change in disease
      states). MATERIALS AND METHODS: Dilatational viscoelasticity (E) was measured
      using an oscillating pendant drop method. Measurements were carried out on spread
      films at the air-water interface as a function of frequency (0.1256-12.56 rad/s)
      at various temperatures between 18-43  degrees C. RESULTS: Generally, E gradually
      decreased as the overall temperature was increased. At both 37 and 20  degrees C,
      films demonstrated that the elastic modulus (E') was more dominant than the
      viscous modulus (E"), indicating films were more solid-like than fluid-like,
      regardless of temperature. E' and E" were also dependant on frequency, indicating
      some molecular rearrangements of the lipid molecules as films were compressed and
      expanded. Films seeded with cholesterol or beta-carotene showed a modest increase
      in the moduli. CONCLUSIONS: These results are consistent with previous findings
      which have predicted and indicated that the meibomian lipid layer is a
      viscoelastic film at the air-liquid interface. These properties are integral to
      how the tear film lipid layer is able to maintain its structure, and hence
      integrity of the ocular surface.

PMID- 23531045
TI  - The association between social relationships and self-harm: a case-control study
      in Taiwan.
AB  - BACKGROUND: Although suicide has been postulated as a result of social breakdown,
      relatively little attention has been paid to the association between social
      relationships and non-fatal self-harm. We sought to investigate the extent to
      which social factors correlate with self-harm in this case-control study.
      METHODS: The primary outcome was self-harm with hospital presentation. Cases of
      self-harm from the Emergency Department in a general hospital in Northern Taiwan
      were recruited, and individually age-and-gender-matched control participants were
      recruited from non-psychiatric outpatient clinics at the same hospital. The Close
      Persons Questionnaire was administered and its social support and social network
      subscales were used to measure social relationships in the 12 months prior to the
      interview. Other covariates, comprising sociodemographic factors, major life
      events, physical and mental health, were adjusted in conditional logistic
      regression models. RESULTS: A total of 124 case-control pairs were recruited. The
      mean (standard deviation) age of the case group was 34.7 (12.8) years and 80.6%
      were female. Higher social isolation score remained significantly associated with
      self-harm after adjustment (adjusted odds ratio per standard deviation increase
      2.92, 95% confidence interval 1.44-5.95) and household size was negatively
      associated with the outcome (adjusted odds ratio per unit increase 0.54, 95% CI
      0.32-0.94). CONCLUSIONS: More limited social networks were associated with self
      harm after adjustment for potential confounders. Enhancing social structure and
      effective networking of people with self-harm to community resources may be
      important for self-harm management in Asian societies and elsewhere.

PMID- 23531046
TI  - A DNAzyme-gold nanoparticle probe for uranyl ion in living cells.
AB  - DNAzymes have shown great promise as a general platform for detecting metal ions,
      as many metal-specific DNAzymes can be obtained using in vitro selection. While
      DNAzyme-based metal sensors have found many applications in the extracellular
      environment, no intracellular application of DNAzyme sensors has yet been
      reported. Here, we demonstrate a novel type of metal ion sensor for intracellular
      metal ion detection. The probe consists of a 13 nm gold nanoparticle (AuNP) core
      functionalized with a shell consisting of a uranyl-specific 39E DNAzyme whose
      enzyme strand contains a thiol at the 3' end for conjugation to the AuNP, and
      whose substrate strand is modified with a Cy3 fluorophore at the 5' end and a
      molecular quencher at the 3' end. In the absence of uranyl, the fluorescence of
      the Cy3 is quenched by both AuNP and the molecular quencher. In the presence of
      uranyl, the DNAzyme cleaves the fluorophore-labeled substrate strand, resulting
      in release of the shorter product strand containing the Cy3 and increased
      fluorescence. We demonstrate that this DNAzyme-AuNP probe can readily enter cells
      and can serve as a metal ion sensor within a cellular environment, making it the
      first demonstration of DNAzymes as intracellular metal ion sensors. Such a method
      can be generally applied to the detection of other metal ions using other
      DNAzymes selected through in vitro selection.

PMID- 23531047
TI  - Proteomic analysis of elite soybean Jidou17 and its parents using iTRAQ-based
      quantitative approaches.
AB  - BACKGROUND: Derived from Hobbit as the female parent and Zao5241 as the male
      parent, the elite soybean cultivar Jidou17 is significantly higher yielding and
      shows enhanced qualities and stronger resistance to non-biological stress than
      its parents. The purpose of this study is to understand the difference in protein
      expression patterns between Jidou17 and its parental strains and to evaluate the
      parental contributions to its elite traits. RESULTS: Leaves (14 days old) from
      Jidou17 and its parental cultivars were analysed for differential expressed
      proteins using an iTRAQ-based (isobaric tags for relative and absolute
      quantitation) method. A total of 1269 proteins was detected, with 141 and 181
      proteins in Jidou17 differing from its female and male parent, respectively.
      Functional classification and an enrichment analysis based on biological
      functions, biological processes, and cellular components revealed that all the
      differential proteins fell into many functional categories but that the number of
      proteins varied greatly for the different categories, with enrichment in specific
      categories. A pathway analysis indicated that the differentiated proteins were
      mainly classified into the ribosome assembly pathway. Protein expression
      clustering results showed that the expression profiles between Jidou17 and its
      female parent Hobbit were more similar than those between Jidou17 and its male
      parent Zao5241 and between the two parental strains. Therefore, the female parent
      Hobbit contributed more to the Jidou17 genotype. CONCLUSIONS: This study applied
      a proven technique to study proteomics in 14-day-old soybean leaves and explored
      the depth and breadth of soybean protein research. The results provide new data
      for further understanding the mechanisms of elite cultivar development.

PMID- 23531048
TI  - Solvent-mediated vibrational energy relaxation from Vaska's complex adducts in
      binary solvent mixtures.
AB  - A vibrational pump-probe and FTIR study was performed on two different adducts of
      Vaska's complex in two different sets of binary solvent mixtures. The carbonyl
      vibrational mode in the oxygen adduct exhibits solvatochromic shifts of ~10 cm(
      1) in either benzyl alcohol or chloroform relative to benzene-d6, whereas this
      vibration is nearly unchanged for the iodine adduct for the same three solvents.
      The width and center frequency of the carbonyl stretch for each adduct are
      compared to its vibrational lifetime in binary mixtures of benzene-d6 with either
      benzyl alcohol or chloroform. In neat solvents, the trends in line width,
      frequency, and vibrational lifetime are consistent for the two adducts, but
      complex relationships emerge when the trends in each property are compared as a
      function of mixed solvent composition. nu(CO) is more sensitive to the solvation
      environment around the trans ligand, whereas the line width and lifetime depend
      on the environment around the CO group itself. The carbonyl frequency and width
      vary nonlinearly across the two binary solvent series, indicating preferential
      solvation. In contrast, the vibrational lifetime changes linearly with solvent
      composition and is correlated with the mole fraction of chloroform but
      anticorrelated with the mole fraction of benzyl alcohol. The results are
      explained by differences in the densities of solvent modes that affect
      intermolecular relaxation of the carbonyl mode.

PMID- 23531049
TI  - Effect of colibacillosis or coccidiosis on expression of breast cancer resistance
      protein in small intestine and liver of chickens.
AB  - Breast cancer resistance protein (BCRP, ABCG2) is a member of ABC (ATP-binding
      cassette) transporter superfamily that occurs in a variety of tissues including
      liver and small intestine of animals. As BCRP is involved in drug absorption,
      distribution, and elimination, modulation of its expression may affect the
      clinical efficacy of drugs. However, little is known about the effects of
      coccidiosis or colibacillosis infection on the levels of BCRP expression in
      chickens. Here, we studied the effect of infection with Escherichia coli (E.
      coli) or Eimeriida mixture (E. necatrix and E. tenella) on the expression levels
      of ABCG2 mRNA and BCRP in the different segments of small intestine and liver in
      chickens. Expression of ABCG2 mRNA or BCRP was detected in the entire small
      intestine and liver of healthy chickens, and the expression levels in liver and
      ileum were significantly higher than duodenum and jejunum. Infection with E. coli
      or Eimeriida mixture resulted in significant decrease in ABCG2 mRNA and BCRP
      expression in liver, ileum, and jejunum, but not in duodenum, in comparison with
      noninfection control. The results indicate that coccidiosis or colibacillosis
      infection inhibits BCRP expression in chickens, which may consequently influence
      drug distribution and therapeutic efficacy.

PMID- 23531050
TI  - Pregnancy test taking is a correlate of unsafe sex, contraceptive nonadherence,
      pregnancy, and sexually transmitted infections in adolescent and young adult
      women.
AB  - OBJECTIVES: This study was conducted to examine the hypotheses that adolescent
      and young adult pregnancy test takers are at increased risk for unsafe sex, oral
      contraception (OC) nonadherence, and higher pregnancy and sexually transmitted
      infection (STI) rates. METHODS: We conducted secondary analyses using data
      collected for a study on OC adherence among 1155 women 16-24 years of age. Data
      collected at baseline and 3, 6, and 12 months were used for the analyses.
      RESULTS: At baseline, 33% of women reported having undergone >=1 pregnancy test
      at home or a clinic during the past 3 months. Pregnancy test takers were more
      likely to have >=3 sexual partners (odds ratio [OR] 2.12; 95% confidence interval
      [CI] 1.49-3.02) in the past year, report unprotected oral (OR 1.48; 95% CI 1.28
      1.72) or anal sex (OR 1.78; 95% CI 1.32-2.39), be diagnosed with an STI (OR 1.76;
      95% CI 1.23-2.51), become pregnant (hazards ratio 1.52; 95% CI 1.10-2.10), or not
      use any birth control method (OR 2.11; 95% CI 1.66-2.60). Moreover, they were
      less likely to continue using OC that was prescribed at baseline (OR 0.38; 95% CI
      0.31-0.47) and to report being ambivalent about pregnancy (OR 0.73; 95% CI 0.60
      0.90) compared to non-test takers. CONCLUSIONS: Pregnancy test taking is an
      important correlate of high-risk sexual behaviors, OC nonadherence, and risk of
      subsequent pregnancy and STIs among adolescent and young adult women. Future
      interventions should target these women to decrease the risk of unintended
      pregnancies and STIs.

PMID- 23531051
TI  - Obesity and risk of breast cancer mortality in Hispanic and Non-Hispanic white
      women: the New Mexico Women's Health Study.
AB  - Obesity is reported to be associated with poorer survival in women with breast
      cancer, regardless of menopausal status. Our purpose was to determine if the
      associations of obesity with breast cancer-specific, all-cause, and non-breast
      cancer mortality differ between Hispanic and non-Hispanic white (NHW) women with
      breast cancer. Data on lifestyle and medical history were collected for incident
      primary breast cancer cases (298 NHW, 279 Hispanic) in the New Mexico Women's
      Health Study. Mortality was ascertained through the National Death Index and New
      Mexico Tumor Registry over 13 years of follow-up. Adjusted Cox regression models
      indicated a trend towards increased risk for breast cancer-specific mortality in
      obese NHW women (hazard ratio [HR] 2.07; 95% confidence interval [CI] 0.98-4.35)
      but not in Hispanic women (HR 1.32; 95% CI 0.64-2.74). Obese NHW women had a
      statistically significant increased risk for all-cause mortality (HR 2.12; 95% CI
      1.15-3.90) while Hispanic women did not (HR 1.23; 95% CI 0.71-2.12). Results were
      similar for non-breast cancer mortality: NHW (HR 2.65; 95% CI 0.90-7.81);
      Hispanic (HR 2.18; 95% CI 0.77-6.10). Our results suggest that obesity is
      associated with increased risk for breast cancer-specific mortality in NHW women;
      however, this association is attenuated in Hispanic women.

PMID- 23531052
TI  - Spatio-temporal variations in the molecular diversity of microeukaryotes in
      particular ciliates in soil of the Yellow River delta, China.
AB  - The Yellow River delta in China is one of the most active regions of land-ocean
      interaction. It has suffered serious salinization due to drying-up of the Yellow
      River, rising sea level, and seashore erosion, and thus represents a special and
      extreme environment. We evaluated the microeukaryotic molecular diversity and its
      response to change of seasons and environmental variables, in particular salinity
      in the soil of the Yellow River delta, by denaturing gradient gel electrophoresis
      (DGGE) and gene sequencing. The sequencing of the microeukaryotic DGGE bands
      revealed the presence of diverse groups dominated by protists in particular
      ciliates. We further recovered a high diversity of marine and soil ciliates
      inhabiting in coastal soil using the ciliate-specific DGGE. The neighbor-joining
      tree indicated that the ciliate 18S rDNA sequences from high-salinity soil were
      affiliated to Colpodea, Spirotrichea, Litostomatea, and Oligohymenophorea, while
      all the sequences unique to the low-salinity soil were affiliated to Colpodea.
      Statistical analysis indicated that the microeukaryotic molecular diversity was
      significantly different among sites, while statistically indistinguishable among
      seasons. Soil salinity might be the main factor regulating the distribution of
      microeukaryotes in the soil from the Yellow River delta.

PMID- 23531053
TI  - Solitary and multiple tumors of follicular infundibulum: a review of 168 cases
      with emphasis on staining patterns and clinical variants.
AB  - BACKGROUND: Tumor of the follicular infundibulum (TFI) is an uncommon benign
      adnexal tumor that usually presents as a solitary keratotic papule in the head
      and neck area. Infrequently, it may present as multiple lesions or in association
      with other conditions. Although it was initially described in 1961, the
      pathogenesis of this lesion is still controversial. METHODS: The clinical and
      histologic features of 168 cases of TFI were reviewed. Random cases were stained
      with elastic Van Gieson, cytokeratin (CK)20 and Ber-EP4. Clinical data and
      clinical images were collected. RESULTS: The median age at presentation was 66
      years with a slight female predominance. As subset of patients (7.7%) had
      multiple TFI, some of which presented with hypopigmented lesions of the head and
      neck area. TFI has a unique staining pattern; all cases tested showed a brush
      like network of elastin fibers, no cases stained for Ber-EP4 and 91.7% of cases
      show single cell positivity to CK20. This is in contrast to basal cell carcinoma
      used for comparison purposes. CONCLUSION: TFI is a distinct neoplastic entity
      with a unique staining pattern and variable clinical presentation. One should be
      aware of the potential clinical presentation of multiple TFI as hypopigmented
      lesions especially in the head and neck area.

PMID- 23531054
TI  - Health outcomes among non-Caucasian living kidney donors: knowns and unknowns.
AB  - The growth in living kidney donation has been accompanied by greater racial
      diversity. Most information on post-donation health comes from single-center
      studies of dominantly Caucasian cohorts. Recent linkage of U.S. donor
      registration data with death records demonstrated higher mortality risks among
      African American donors, but importantly, no differences in death compared with
      demographically matched, healthy controls. Within the donor population, some
      recent studies have also identified higher likelihoods of post-donation
      hypertension, diabetes mellitus and kidney failure in African American and
      Hispanic donors. Thus, based on concerns for higher risks of long-term end-organ
      damage, it may be reasonable to consider race within the living donor selection
      process, such as use of more stringent exclusion criteria among non-Caucasian
      living donors with baseline elevated blood pressure. Recently identified
      associations of coding variants in the apolipoprotein L1 (APOL1) gene with
      nondiabetic renal failure in African Americans raise promise of APOL1 genotyping
      as a novel tool for risk stratifying African American potential donors, but more
      data are needed to understand implications for post-donation outcomes. To tailor
      counseling and informed consent, focused attention to long-term medical outcomes
      among non-Caucasian living donors is needed, and should include assembly of
      healthy non-donor controls for assessment of attributable risks of donation. 

PMID- 23531055
TI  - Thyroid hormone actions are temperature-specific and regulate thermal acclimation
      in zebrafish (Danio rerio).
AB  - BACKGROUND: Thyroid hormone (TH) is best known for its role in development in
      animals, and for its control of metabolic heat production (thermogenesis) during
      cold acclimation in mammals. It is unknown whether the regulatory role of TH in
      thermogenesis is derived in mammals, or whether TH also mediates thermal
      responses in earlier vertebrates. Ectothermic vertebrates show complex responses
      to temperature variation, but the mechanisms mediating these are poorly
      understood. The molecular mechanisms underpinning TH action are very similar
      across vertebrates, suggesting that TH may also regulate thermal responses in
      ectotherms. We therefore aimed to determine whether TH regulates thermal
      acclimation in the zebrafish (Danio rerio). We induced hypothyroidism, followed
      by supplementation with 3,5-diiodothyronine (T2) or 3,5,3'-triiodothyronine (T3)
      in zebrafish exposed to different chronic temperatures. We measured whole-animal
      responses (swimming performance and metabolic rates), tissue-specific regulatory
      enzyme activities, gene expression, and free levels of T2 and T3. RESULTS: We
      found that both T3 and the lesser-known T2, regulate thermal acclimation in an
      ectotherm. To our knowledge, this is the first such study to show this.
      Hypothyroid treatment impaired performance measures in cold-acclimated but not
      warm-acclimated individuals, whereas supplementation with both TH metabolites
      restored performance. TH could either induce or repress responses, depending on
      the actual temperature and thermal history of the animal. CONCLUSIONS: The low
      sensitivity to TH at warm temperatures could mean that increasing temperatures
      (that is, global warming) will reduce the capacity of animals to regulate their
      physiologies to match demands. We suggest that the properties that underlie the
      role of TH in thermal acclimation (temperature sensitivity and metabolic control)
      may have predisposed this hormone for a regulatory role in the evolution of
      endothermy.

PMID- 23531056
TI  - Effects of climate change, invasive species, and disease on the distribution of
      native European crayfishes.
AB  - Climate change will require species to adapt to new conditions or follow
      preferred climates to higher latitudes or elevations, but many dispersal-limited
      freshwater species may be unable to move due to barriers imposed by watershed
      boundaries. In addition, invasive nonnative species may expand into new regions
      under future climate conditions and contribute to the decline of native species.
      We evaluated future distributions for the threatened European crayfish fauna in
      response to climate change, watershed boundaries, and the spread of invasive
      crayfishes, which transmit the crayfish plague, a lethal disease for native
      European crayfishes. We used climate projections from general circulation models
      and statistical models based on Mahalanobis distance to predict climate-suitable
      regions for native and invasive crayfishes in the middle and at the end of the
      21st century. We identified these suitable regions as accessible or inaccessible
      on the basis of major watershed boundaries and present occurrences and evaluated
      potential future overlap with 3 invasive North American crayfishes. Climate
      suitable areas decreased for native crayfishes by 19% to 72%, and the majority of
      future suitable areas for most of these species were inaccessible relative to
      native and current distributions. Overlap with invasive crayfish plague
      transmitting species was predicted to increase. Some native crayfish species
      (e.g., noble crayfish [Astacus astacus]) had no future refugia that were
      unsuitable for the modeled nonnative species. Our results emphasize the
      importance of preventing additional introductions and spread of invasive
      crayfishes in Europe to minimize interactions between the multiple stressors of
      climate change and invasive species, while suggesting candidate regions for the
      debatable management option of assisted colonization.

PMID- 23531058
TI  - Comparison between manual aspiration via polyethylene tubing and aspiration via a
      suction pump with a suction trap connection for performing bronchoalveolar lavage
      in healthy dogs.
AB  - OBJECTIVE: To compare the diagnostic quality of bronchoalveolar lavage (BAL)
      fluid acquired from healthy dogs by manual aspiration via polyethylene tubing
      (MAPT) and via suction pump aspiration (SPA) with a suction trap connection.
      ANIMALS: 12 healthy adult Beagles. PROCEDURES: BAL was performed with
      bronchoscopic guidance in anesthetized dogs. The MAPT was performed with a 35-mL
      syringe attached to polyethylene tubing wedged in a bronchus via the
      bronchoscope's biopsy channel. The SPA was performed with 5 kPa of negative
      pressure applied to the bronchoscope's suction valve via a suction trap. The MAPT
      and SPA techniques were performed in randomized order on opposite caudal lung
      lobes of each dog. Two 1 mL/kg lavages were performed per site. Samples of BAL
      fluid were analyzed on the basis of a semiquantitative quality scale, percentage
      of retrieved fluid, and total nucleated and differential cell counts. Results
      were compared with Wilcoxon signed rank tests. RESULTS: Percentage of BAL fluid
      retrieved (median difference, 16.2%), surfactant score (median difference, 1),
      and neutrophil count (median difference, 74 cells/MUL) were significantly higher
      for SPA than for MAPT. A higher BAL fluid epithelial cell score was obtained via
      MAPT, compared with that for samples obtained via SPA (median difference, 1).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that in healthy dogs, SPA
      provided a higher percentage of BAL fluid retrieval than did MAPT. The SPA
      technique may improve the rate of diagnostic success for BAL in dogs, compared
      with that for MAPT. Further evaluation of these aspiration techniques in dogs
      with respiratory tract disease is required.

PMID- 23531059
TI  - Physiologic and antinociceptive effects following intramuscular administration of
      xylazine hydrochloride in combination with tiletamine-zolazepam in llamas.
AB  - OBJECTIVE: To evaluate antinociceptive and selected effects associated with IM
      administration of xylazine hydrochloride in combination with tiletamine-zolazepam
      in llamas. ANIMALS: 8 adult male llamas. Procedures-Each llama received
      tiletamine-zolazepam (2 mg/kg) combined with either xylazine (0.1, 0.2, or 0.4
      mg/kg) or saline (0.9% NaCl) solution IM (treatments designated as TZ-Xy0.1, TZ
      Xy0.2, TZ-Xy0.4, and TZ-Sal, respectively) at 1-week intervals. Selected
      cardiorespiratory variables were assessed during lateral recumbency and
      anesthesia, and recovery characteristics were recorded. Duration of
      antinociception was evaluated by clamping a claw every 5 minutes. RESULTS:
      Interval between treatment administration and lateral recumbency for TZ-Xy0.4 was
      shorter than that for TZ-Xy0.1 or TZ-Sal. Mean +/- SEM duration of
      antinociception was longer for TZ-Xy0.4 (51.3 +/- 7. 0 minutes), compared with
      findings for TZ-Xy0.2 (31.9 +/- 6.0 minutes), TZ-Xy0.1 (8.1 +/- 4.0 minutes), and
      TZ-Sal (0.6 +/- 0.6 minutes). Interval between treatment administration and
      standing was longer for TZ-Xy0.4 (112 +/- 9 minutes) than it was for TZ-Xy0.2 (77
      +/- 9 minutes) or TZ-Sal (68 +/- 9 minutes). Mean heart and respiratory rates
      during the first 30 minutes for TZ-Sal exceeded values for the other treatments.
      Administration of TZ-Xy0.2 and TZ-Xy0.4 resulted in Pao2 < 60 mm Hg at 5 minutes
      after llamas attained lateral recumbency, and values differed from TZ-Sal
      findings at 5, 10, and 15 minutes; Paco2 was greater for TZ-Xy0.2 and TZ-Xy0.4
      than for TZ-Sal at 5, 10, 15, and 20 minutes. CONCLUSIONS AND CLINICAL RELEVANCE:
      Xylazine (0.2 and 0.4 mg/kg) increased the duration of antinociception in llamas
      anesthetized with tiletamine-zolazepam.

PMID- 23531060
TI  - Comparison of overground and treadmill-based gaits of dogs.
AB  - OBJECTIVE: To compare overground and treadmill-based gaits of dogs. ANIMALS: 5
      clinically normal adult mixed-breed dogs. PROCEDURES: To obtain dynamic gait
      data, 30 retroreflective markers were affixed bilaterally to specific regions of
      the hind limbs and pelvis of each dog. For each dog, 3-D joint motion data
      (sagittal [flexion and extension], transverse [internal and external rotation],
      and frontal [abduction and adduction] planes of motion) for the hip,
      femorotibial, and tarsal joints were acquired during walking and trotting through
      a calibrated testing space overground or on a treadmill. Comparison of data was
      performed via generalized indicator function analysis and Fourier analysis.
      RESULTS: Both overground and treadmill-based gaits produced similar waveforms in
      all planes of motion. Fourier analysis revealed no difference between overground
      and treadmill-based gaits in the sagittal plane of motion; however, small
      differences were detected between overground and treadmill-based gaits in the
      other 2 planes of motion. Additionally, femorotibial joint motion during walking
      did not differ among planes of motion. Generalized indicator function analysis
      was able to detect differences between overground and treadmill-based gait
      waveforms in all planes of motion for all joints during walking and trotting.
      CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, overground and treadmill-based gaits
      produced similar waveform shapes. Of the 3 planes of motion evaluated, only
      sagittal plane kinematic gait data were unaffected by mode of ambulation as
      determined via Fourier analysis. Sagittal kinematic gait data collected from dogs
      during overground or treadmill-based ambulation were comparable. However,
      analysis methods may affect data comparisons.

PMID- 23531061
TI  - Histomorphometric evaluation of the effect of early exercise on subchondral
      vascularity in the third carpal bone of horses.
AB  - OBJECTIVE: To investigate histomorphometric changes in the cartilage and
      subchondral bone of the third carpal bone associated with conditioning exercise
      in young Thoroughbreds. ANIMALS: Nine 18-month-old Thoroughbreds. Procedures-Both
      third carpal bones of 9 horses (4 exercised spontaneously at pasture only and 5
      given additional conditioning exercise beginning at a mean age of 3 weeks) were
      evaluated. Histomorphometric variables (hyaline and calcified cartilage thickness
      and collagen orientation; vascular channel area, number, and orientation; and
      osteochondral junction rugosity) of the third carpal bone, sampled at 4
      dorsopalmar sites in the radial facet, were compared between the exercised and
      nonexercised groups. RESULTS: The vascular channel area measured at the 4
      dorsopalmar sites was larger in the exercised group than in the control group,
      but none of the variables were significantly different between groups. Both
      groups had significant site-specific variations in all measured variables. Most
      importantly, the vascular channel area was highest in the most dorsal aspect.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the mild exercise
      imposed in both groups during the developmental period appeared to be associated
      with an increase in the vascular channel area beneath the calcified cartilage
      layer in the third carpal bone. This increased vascular channel area could also
      be associated with high stress in the dorsal aspect of the radial facet, a region
      that is known to be vulnerable to osteochondral fragmentation.

PMID- 23531062
TI  - Pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses.
AB  - OBJECTIVE: To determine the pharmacokinetics, pharmacodynamics, and safety of
      zoledronic acid in horses. ANIMALS: 8 healthy horses. PROCEDURES: A single dose
      of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period.
      Venous blood was collected at several time points. Zoledronic acid concentration
      in plasma was measured by liquid chromatography-tandem mass spectrometry, and
      pertinent pharmacokinetic parameters were determined. Plasma was analyzed for
      total calcium, BUN, and creatinine concentrations and a marker for bone
      resorption (C-terminal telopeptides of type I collagen). RESULTS: Zoledronic acid
      was safely administered IV during a 30-minute period, and no adverse effects were
      observed. Plasma concentrations of zoledronic acid were consistent with a 2
      compartment mammillary model. Plasma concentrations of zoledronic acid were
      detected for up to 8 hours after administration. Mean total calcium
      concentrations in plasma were less than the reference range 7 days after
      zoledronic acid administration. A marker for bone remodeling decreased in
      concentration after zoledronic acid administration and remained low for the 1
      year duration of the study. No changes in BUN and creatinine concentrations were
      observed after zoledronic acid administration. CONCLUSIONS AND CLINICAL
      RELEVANCE: Zoledronic acid was safely administered in healthy horses. Zoledronic
      acid is reported as the strongest bisphosphonate presently available, and studies
      evaluating potential benefits of zoledronic acid in horses with orthopedic
      conditions are warranted.

PMID- 23531063
TI  - Effect of water depth on amount of flexion and extension of joints of the distal
      aspects of the limbs in healthy horses walking on an underwater treadmill.
AB  - OBJECTIVE: To determine the maximum amount of flexion and extension of the
      carpal, tarsal, metacarpophalangeal, and metatarsophalangeal joints and the
      percentage duration of the stance and swing phases of the stride for horses
      walking on an underwater treadmill in various water depths. ANIMALS: 9 healthy
      adult horses. PROCEDURES: Zinc oxide markers were placed on the forelimbs and
      hind limbs of the horses. Video was recorded of horses walking (0.9 m/s) on an
      underwater treadmill during baseline conditions (< 1 cm of water) or in various
      amounts of water (level of the metatarsophalangeal, tarsal, and stifle joints).
      Maximum amount of joint flexion and extension, range of motion (ROM), and the
      percentage durations of the stance and swing phases of the stride were determined
      with 2-D motion analysis software. RESULTS: The ROM was greater for all evaluated
      joints in any amount of water versus ROM for joints in baseline conditions
      (primarily because of increases in amount of joint flexion). The greatest ROM for
      carpal joints was detected in a tarsal joint water depth, for tarsal joints in a
      stifle joint water depth, and for metacarpophalangeal and metatarsophalangeal
      joints in metatarsophalangeal and tarsal joint water depths. As water depth
      increased, the percentage durations of the stance and swing phases of the stride
      significantly decreased and increased, respectively. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results of this study suggested that exercise on an underwater
      treadmill is useful for increasing the ROM of various joints of horses during
      rehabilitation and that the depth of water affects the amount of flexion and
      extension of joints.

PMID- 23531064
TI  - In vitro effects of lipid emulsion on platelet function and thromboelastography
      in canine blood samples.
AB  - OBJECTIVE: To determine whether soybean oil emulsion has an in vitro effect on
      platelet aggregation and thromboelastography in blood samples obtained from
      healthy dogs. ANIMALS: 12 healthy adult dogs. PROCEDURES: Blood samples were
      collected from each dog into tubes containing EDTA, hirudin, or sodium citrate
      for a CBC, collagen- and ADP-induced impedance aggregometry, or
      thromboelastography, respectively. Whole blood platelet aggregation, determined
      with ADP or collagen agonists, was measured in blood samples containing hirudin
      and final lipid concentrations of 0, 1, 10, and 30 mg/mL. The
      thromboelastographic variables R (reaction time), K (clotting time), alpha angle,
      and maximum amplitude were evaluated in blood samples containing sodium citrate
      and final lipid concentrations equivalent to those used for assessment of
      platelet aggregation. RESULTS: Median maximum ADP- and collagen-induced platelet
      aggregation in blood samples containing 1, 10, or 30 mg of lipid/mL did not
      differ significantly from the value for the respective lipid-free blood sample.
      Maximum amplitude determined via thromboelastography was significantly reduced in
      blood samples containing 10 and 30 mg of lipid/mL, compared with findings for
      lipid-free blood samples. Values of other thromboelastographic variables did not
      differ, regardless of lipid concentrations. CONCLUSIONS AND CLINICAL RELEVANCE:
      Maximum amplitude determined via thromboelastography in canine blood samples was
      significantly affected by the addition of lipid to final concentrations that are
      several orders of magnitude higher than clinically relevant lipid concentrations
      in dogs. Lipid treatment appears to have no significant effect on hemostatic
      variables in dogs, although clinical studies should be performed to confirm these
      in vitro findings.

PMID- 23531065
TI  - Computed tomographic characterization of the pulmonary system in clinically
      normal alpacas.
AB  - OBJECTIVE: To characterize and quantitatively assess the typical pulmonary
      anatomy of healthy adult alpacas with multidetector row CT. ANIMALS: 10
      clinically normal adult female alpacas. PROCEDURES: CT examination of the thorax
      was performed before and after IV administration of iodinated contrast medium in
      sedated alpacas in sternal recumbency. Measurements of the trachea, bronchi and
      related blood vessels, and selected vertebrae as well as the extent and density
      of lung parenchyma were performed with a Digital Imaging and Communications in
      Medicine (DICOM) viewer. Morphometric and quantitative data were summarized.
      RESULTS: Separation of individual lung lobes could not be identified, except for
      the accessory lung lobe. In all alpacas, both lungs extended farther caudally at
      the medial aspect than at the lateral aspect. The right lung extended farther in
      both cranial and caudal directions than did the left lung. The branching pattern
      of the bronchial tree varied only slightly among alpacas and consisted of 1
      cranial bronchus and 3 caudal bronchi bilaterally, with a right accessory
      bronchus. Luminal diameters of first-generation bronchi ranged from 3 to 9 mm.
      Mean +/- SD parenchymal lung density was -869 +/- 40 Hounsfield units (HU) before
      contrast injection and -825 +/- 51 HU after contrast injection. Mean difference
      in diameter between bronchi and associated arteries or veins was 0.8 +/- 0.9 mm.
      CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of the typical anatomy of the lungs
      and bronchial tree in healthy alpacas as determined via CT will aid veterinarians
      in clinical assessment and bronchoscopic evaluation of alpacas.

PMID- 23531066
TI  - In vivo and in vitro effects of neostigmine on gastrointestinal tract motility of
      horses.
AB  - OBJECTIVE: To determine the response to neostigmine of the contractile activity
      of the jejunum and pelvic flexure and the effects of a continuous rate infusion
      (CRI) of neostigmine in horses. ANIMALS: 7 adult horses and tissue from 12 adult
      horses. PROCEDURES: A CRI of neostigmine (0.008 mg/kg/h) or placebo was
      administered to 6 horses in a crossover study design. Gastric emptying was
      evaluated by the acetaminophen test. The frequency of defecation and urination
      and the consistency and weight of feces were recorded throughout the experiment.
      The effect of neostigmine on smooth muscle contractile activity was evaluated in
      tissues from the jejunum and pelvic flexure. The effect of neostigmine and
      acetylcholine after incubation with muscarinic receptor antagonists (atropine and
      DAU 5884) and an acetylcholinesterase inhibitor (edrophonium) was also
      investigated in vitro. RESULTS: No difference was observed between neostigmine
      and placebo for time to reach peak plasma acetaminophen concentration and
      absorption rate constant. A CRI of neostigmine increased fecal production and
      frequency of urination. Neostigmine induced a dose-dependent increase of
      contractile amplitude in jejunum and pelvic flexure muscle strips. Incubation of
      muscle strips with atropine and DAU 5884 inhibited the response to acetylcholine
      and neostigmine. Incubation of smooth muscle strips from the jejunum with
      edrophonium increased the response to acetylcholine and had no effect on the
      response to neostigmine in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: A CRI of
      neostigmine increased fecal production and urination frequency in horses. A CRI
      of neostigmine did not decrease gastric emptying. Neostigmine stimulated
      contractile activity of jejunum and pelvic flexure smooth muscle strips in vitro.

PMID- 23531067
TI  - Comparison of inferred fractions of n-3 and n-6 polyunsaturated fatty acids in
      feral domestic cat diets with those in commercial feline extruded diets.
AB  - OBJECTIVE: To compare presumed fatty acid content in natural diets of feral
      domestic cats (inferred from body fat polyunsatrated fatty acids content) with
      polyunsaturated fatty acid content of commercial feline extruded diets. SAMPLE:
      Subcutaneous and intra-abdominal adipose tissue samples (approx 1 g) from
      previously frozen cadavers of 7 adult feral domestic cats trapped in habitats
      remote from human activity and triplicate samples (200 g each) of 7 commercial
      extruded diets representing 68% of market share obtained from retail stores.
      PROCEDURES: Lipid, triacylglycerol, and phospholipid fractions in adipose tissue
      samples and ether extracts of diet samples were determined by gas chromatography
      of methyl esters. Triacylglycerol and phospholipid fractions in the adipose
      tissue were isolated by thin-layer chromatography. Diet samples were also
      analyzed for proximate contents. RESULTS: For the adipose tissue samples, with
      few exceptions, fatty acids fractions varied only moderately with lipid fraction
      and site from which tissue samples were obtained. Linoleic, alpha-linolenic,
      arachidonic, eicosapentaenoic, and docosahexaenoic acid fractions were 15.0% to
      28.2%, 4.5% to 18.7%, 0.9% to 5.0%, < 0.1% to 0.2%, and 0.6% to 1.7%,
      respectively. As inferred from the adipose findings, dietary fractions of
      docosahexaenoic and alpha-linolenic acid were significantly greater than those in
      the commercial feline diets, but those for linoleic and eicosapentaenoic acids
      were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: The fatty
      acid content of commercial extruded feline diets differed from the inferred
      content of natural feral cat diets, in which dietary n-3 and possibly n-6
      polyunsaturated fatty acids were more abundant. The impact of this difference on
      the health of pet cats is not known.

PMID- 23531068
TI  - Comparison of pathological changes and viral antigen distribution in tissues of
      calves with and without preexisting bovine viral diarrhea virus infection
      following challenge with bovine herpesvirus-1.
AB  - OBJECTIVE: To compare pathological changes and viral antigen distribution in
      tissues of calves with and without preexisting subclinical bovine viral diarrhea
      virus (BVDV) infection following challenge with bovine herpesvirus-1 (BHV-1).
      ANIMALS: 24 Friesian calves. PROCEDURES: 12 calves were inoculated intranasally
      with noncytopathic BVDV-1a; 12 days later, 10 of these calves were challenged
      intranasally with BHV-1 subtype 1. Two calves were euthanized before and 1, 2, 4,
      7, or 14 days after BHV-1 inoculation. Another 10 calves were inoculated
      intranasally with BHV-1 only and euthanized 1, 2, 4, 7, or 14 days later. Two
      calves were inoculated intranasally with virus-free tissue culture fluid and
      euthanized as negative controls. Pathological changes and viral antigen
      distribution in various tissue samples from calves with and without BVDV
      infection (all of which had been experimentally inoculated with BHV-1) were
      compared. RESULTS: Following BHV-1 challenge, calves with preexisting subclinical
      BVDV infection had earlier development of more severe inflammatory processes and,
      consequently, more severe tissue lesions (limited to lymphoid tissues and
      respiratory and digestive tracts) and greater dissemination of BHV-1, compared
      with calves without preexisting BVDV infection. Moreover, coinfected calves had
      an intense lymphoid depletion in the Peyer patches of the ileum as well as the
      persistence of BVDV in target organs and the reappearance of digestive tract
      changes during disease progression. CONCLUSIONS AND CLINICAL RELEVANCE: In
      calves, preexisting infection with BVDV facilitated the establishment of BHV-1
      infection, just as the presence of BHV-1 favors BVDV persistence, thereby
      synergistically potentiating effects of both viruses and increasing the severity
      of the resultant clinical signs.

PMID- 23531069
TI  - Evaluation of plasma diazepam and nordiazepam concentrations following
      administration of diazepam intravenously or via suppository per rectum in dogs.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of diazepam administered per rectum
      via compounded (ie, not commercially available) suppositories and determine
      whether a dose of 2 mg/kg in this formulation would result in plasma
      concentrations shown to be effective for control of status epilepticus or cluster
      seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10
      to 15 minutes). ANIMALS: 6 healthy mixed-breed dogs. PROCEDURES: Dogs were
      randomly assigned to 2 groups of 3 dogs each in a crossover-design study.
      Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood
      samples were collected at predetermined time points. Following a 6- or 7-day
      washout period, each group received the alternate treatment. Plasma
      concentrations of diazepam and nordiazepam were analyzed via reversed phase high
      performance liquid chromatography. RESULTS: Plasma concentrations of diazepam and
      nordiazepam exceeded the targeted range <= 3 minutes after IV administration in
      all dogs. After suppository administration, targeted concentrations of diazepam
      were not detected in any dogs, and targeted concentrations of nordiazepam were
      detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved
      (1). CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of these results,
      administration of 2 mg of diazepam/kg via the compounded suppositories used in
      the present study cannot be recommended for emergency treatment of seizures in
      dogs.

PMID- 23531070
TI  - Assessment of cord dorsum potentials from caudal nerves in anesthetized
      clinically normal adult dogs without or during neuromuscular blockade.
AB  - OBJECTIVE: To assess the feasibility of measuring cord dorsum potentials (CDPs)
      in anesthetized clinically normal dogs after caudal nerve stimulation, determine
      the intervertebral site of maximum amplitude and best waveform of the CDP, and
      evaluate the effects of neuromuscular blockade. ANIMALS: 8 male and 4 female dogs
      (age, 1 to 5 years). PROCEDURES: Dogs were anesthetized, and CDPs were recorded
      via needles placed on the dorsal lamina at intervertebral spaces L1-2 through L7
      S1. Caudal nerves were stimulated with monopolar electrodes inserted laterally to
      the level of the caudal vertebrae. Dogs were tested without and during
      neuromuscular blockade induced with atracurium besylate. The CDP latency and
      amplitude were determined from the largest amplitude tracings. RESULTS: CDPs were
      recorded in 11 of 12 dogs without neuromuscular blockade and in all dogs during
      neuromuscular blockade. The CDP was largest and most isolated at the L4-5
      intervertebral space (3 dogs) or the L5-6 intervertebral space (9 dogs); this
      site corresponded to the segment of insertion of the first caudal nerve. Onset
      latencies ranged from 2.0 to 4.7 milliseconds, and there was no effect of
      neuromuscular blockade on latencies. Amplitudes of the CDPs were highly variable
      for both experimental conditions. CONCLUSIONS AND CLINICAL RELEVANCE: CDPs were
      recorded from all dogs tested in the study; neuromuscular blockade was not
      critical for successful CDP recording but reduced muscle artifact. This technique
      may be useful as a tool to assess the caudal nerve roots in dogs suspected of
      having compressive lumbosacral disease or myelopathies affecting the lumbar
      intumescence.

PMID- 23531072
TI  - Effects of anesthetic induction with midazolam-propofol and midazolam-etomidate
      on selected ocular and cardiorespiratory variables in clinically normal dogs.
AB  - OBJECTIVE: To compare effects of anesthetic induction with midazolam-propofol or
      midazolam-etomidate on intraocular pressure (IOP), pupillary diameter (PD), pulse
      rate, blood pressure, and respiratory rate in clinically normal dogs. ANIMALS: 18
      dogs. PROCEDURES: Dogs undergoing ophthalmic surgery received midazolam (0.2
      mg/kg, IV) and either propofol or etomidate (IV) until intubatable. For all dogs,
      results of physical examinations, ophthalmic examinations of the nonoperated eye,
      and preanesthetic blood analyses were normal. Intraocular pressure, PD, blood
      pressure, pulse rate, and respiratory rate were measured in the nonoperated eye
      at 5 time points: just prior to the anesthetic induction sequence, after 5
      minutes of preanesthetic oxygenation via face mask, after IV administration of
      midazolam, after IV anesthetic induction, and after endotracheal intubation.
      RESULTS: PD decreased significantly from baseline by 4.4 +/- 0.4 mm (mean +/- SD)
      after anesthetic induction and 5.3 +/- 0.4 mm after intubation in the etomidate
      group and by 1. 2 +/- 0.4 mm after intubation in the propofol group. Intraocular
      pressure was increased significantly from baseline by 3.2 +/- 1.0 mm Hg after
      anesthetic induction in the etomidate group and by 4.7 +/- 1.2 mm Hg after
      anesthetic induction and 4.5 +/- 1. 2 mm Hg after intubation in the propofol
      group. Pulse rate was significantly lower by 28.6 +/- 12.6 beats/min after
      anesthetic induction in the etomidate group, compared with the propofol group.
      CONCLUSIONS AND CLINICAL RELEVANCE: At the studied doses, midazolam-etomidate
      caused clinically important miosis and increased IOP. Midazolam-propofol caused
      an even greater increase in IOP but had minimal effects on PD.

PMID- 23531071
TI  - Western blot patterns of serum autoantibodies against optic nerve antigens in
      dogs with goniodysgenesis-related glaucoma.
AB  - OBJECTIVE: To investigate whether differences existed between clinically normal
      dogs and dogs with goniodysgenesis-related glaucoma (GDRG) in serum
      autoantibodies against optic nerve antigens. ANIMALS: 16 dogs with GDRG, 17
      healthy dogs with unremarkable pectinate ligament and iridocorneal angle
      morphology, and 13 euthanized dogs with no major ocular abnormalities or
      underlying diseases. PROCEDURES: Western blotting was performed with optic nerve
      extracts from the euthanized dogs as an antigen source and serum from clinically
      normal dogs and dogs with GDRG as a primary antibody (autoantibody) source. Blots
      were evaluated for presence and density of bands. RESULTS: Multiple bands were
      identified on western blots from all dogs with GDRG and all clinically normal
      dogs, with a high degree of variability among individual dogs. Dogs with GDRG
      were significantly more likely than healthy dogs to have bands present at 38, 40,
      and 68 kDa. Dogs with GDRG had significant increases in autoreactivity at 40 and
      53 kDa and a significant decrease in autoreactivity at 48 kDa. CONCLUSIONS AND
      CLINICAL RELEVANCE: Significant differences in serum autoantibodies against optic
      nerve antigens were found in dogs with versus without GDRG. Although it remains
      unclear whether these differences were part of the pathogenesis of disease or
      were sequelae to glaucomatous changes, these findings provide support for the
      hypothesis that immune-mediated mechanisms play a role in the development or
      progression of GDRG. However, the high degree of variability among individual
      dogs and the considerable overlap between groups suggest that the clinical
      usefulness of this technique for distinguishing dogs with GDRG from clinically
      normal dogs is likely limited.

PMID- 23531074
TI  - Pharmacokinetics of meloxicam in rabbits after oral administration of single and
      multiple doses.
AB  - OBJECTIVE: To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits
      after oral administration of single and multiple doses. ANIMALS: 6 healthy
      rabbits. PROCEDURES: A single dose of meloxicam (1 mg/kg, PO) was administered to
      the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was
      administered to rabbits every 24 hours for 5 days. Blood samples were obtained
      from rabbits at predetermined intervals during both treatment periods. Plasma
      meloxicam concentrations were determined, and noncompartmental pharmacokinetic
      analysis was performed. RESULTS: The mean peak plasma concentration and area
      under the plasma concentration-versus-time curve extrapolated to infinity after
      administration of a single dose of meloxicam were 0.83 MUg/mL and 10.37 h*MUg/mL,
      respectively. After administration of meloxicam for 5 days, the mean peak plasma
      concentration was 1.33 MUg/mL, and the area under the plasma concentration-versus
      time curve from the time of administration of the last dose to 24 hours after
      that time was 18.79 h*MUg/mL. For single- and multiple-dose meloxicam
      experiments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours
      and the mean terminal half-life was 6.1 and 6.7 hours, respectively. CONCLUSIONS
      AND CLINICAL RELEVANCE: Plasma concentrations of meloxicam for rabbits in the
      present study were proportionally higher than those previously reported for
      rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for
      animals of other species that received clinically effective doses. A dose of 1
      mg/kg may be necessary to achieve clinically effective circulating concentrations
      of meloxicam in rabbits, although further studies are needed.

PMID- 23531075
TI  - Effect of acute exercise on monocarboxylate transporters 1 and 4 in untrained and
      trained Thoroughbreds.
AB  - OBJECTIVE: To evaluate the effects of a single incremental exercise test (IET) on
      mRNA expression and protein content of monocarboxylate transporter (MCT) 1 and
      MCT4 in the gluteus medius muscle of Thoroughbreds. ANIMALS: 12 Thoroughbreds (6
      males and 6 females; age, 3 to 4 years). PROCEDURES: Horses underwent an IET
      before and after 18 weeks of high-intensity exercise training (HIT). Horses were
      exercised at 90% of maximal oxygen consumption for 3 minutes during the initial
      10 weeks of HIT and 110% of maximal oxygen consumption for 3 minutes during the
      last 8 weeks of HIT. Gluteus medius muscle biopsy specimens were obtained from
      horses before (baseline), immediately after, and at 3, 6, and 24 hours after the
      IET. RESULTS: Expression of MCT1 and MCT4 mRNA was upregulated at 3 and 6 hours
      after the IET in muscle specimens obtained from horses prior to HIT (untrained
      horses) and at 6 hours after the IET in muscle specimens obtained from horses
      after HIT (trained horses). For both untrained and trained horses, MCT1 and MCT4
      protein contents were increased at 6 hours after the IET and did not differ at 24
      hours after the IET, compared with those at baseline. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that a single IET resulted in transient increases in
      MCT1 and MCT4 mRNA expression and protein content in untrained and trained
      horses. These results may be important for the elucidation of exercise-induced
      alterations in lactate metabolism.

PMID- 23531076
TI  - Evaluation of glomerular filtration rate in cats with reduced renal mass and
      administered meloxicam and acetylsalicylic acid.
AB  - OBJECTIVE: To determine whether administration of meloxicam or acetylsalicylic
      acid alters glomerular filtration rate (GFR) in cats with renal azotemia.
      ANIMALS: 6 young adult cats. PROCEDURES: 3 sexually intact male cats and 3
      sexually intact female cats had surgically reduced renal mass and azotemia
      comparable to International Renal Interest Society chronic kidney disease stages
      2 and 3. Renal function was evaluated by measurement of serum creatinine
      concentration, urinary clearance of exogenously administered creatinine, and the
      urine protein-to-creatinine concentration ratio (UP:C). Measurements taken in
      cats receiving placebo at the beginning and end of the study were compared with
      results obtained at the end of 7 days of treatment with either meloxicam (0.2
      mg/kg, SC, on day 1; 0.1 mg/kg, SC, on days 2 to 7) or acetylsalicylic acid (20
      mg/kg, PO, on days 1, 4, and 7). RESULTS: No significant treatment effects on
      urinary clearance of exogenously administered creatinine, serum creatinine
      concentration, or UP:C were detected. Mean +/- SEM serum creatinine concentration
      and urinary clearance of exogenously administered creatinine measurements
      following 7 days of treatment with meloxicam (serum creatinine concentration,
      2.67 +/- 0.17 mg/dL; urinary clearance of exogenously administered creatinine,
      1.34 +/- 0.08 mL/min/kg) and acetylsalicylic acid (serum creatinine
      concentration, 2.62 +/- 0.12 mg/dL; urinary clearance of exogenously administered
      creatinine, 1.35 +/- 0.07 mL/min/kg) were not significantly different from the
      mean baseline values for these variables (serum creatinine concentration, 2.77 +/
      0.14 mg/dL; urinary clearance of exogenously administered creatinine, 1.36 +/-
      0.07 mL/min/kg). CONCLUSIONS AND CLINICAL RELEVANCE: Neither meloxicam nor
      acetylsalicylic acid had a measurable effect on urinary clearance of exogenously
      administered creatinine, serum creatinine concentration, or UP:C. These results
      are consistent with the hypothesis that GFR of euvolemic cats with normal or
      reduced renal function is not dependent on cyclooxygenase function.

PMID- 23531077
TI  - Excited state properties of naphtho-homologated xxDNA bases and effect of
      methanol solution, deoxyribose, and base pairing.
AB  - Design and synthesis of fluorescent nucleobase analogues for studying structures
      and dynamics of nucleic acids have attracted much attention in recent years. In
      the present work, a comprehensive theoretical study of electronic transitions of
      naphtho-homologated base analogues, namely, xxC, xxT, xxA, and xxG, was
      performed. The nature of the low-lying excited states was discussed, and the
      results were compared with those of x-bases. Geometrical characteristics of the
      lowest excited singlet pipi* states were explored using the CIS method. The
      calculated excitation maxima are 423, 397, 383, and 357 nm for xxA, xxG, xxC, and
      xxT, respectively, and they are greatly red-shifted compared with x-bases and
      natural bases, allowing them to be selectively excited in the presence of the
      natural bases. In the gas phase, the fluorescence from them would be expected to
      occur around 497, 461, 457, and 417 nm, respectively. The effects of methanol
      solution, deoxyribose, and base paring with their complementary natural bases on
      the relevant absorption and emission spectra of these modified bases were also
      examined.

PMID- 23531078
TI  - The masters talk: the PGC-1alpha-MITF axis as a melanoma energizer.

PMID- 23531079
TI  - A cell-targeted photodynamic nanomedicine strategy for head and neck cancers.
AB  - Photodynamic therapy (PDT) holds great promise for the treatment of head and neck
      (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due
      to the highly aggressive and recurrent nature of the cancers. While interstitial
      light delivery technologies are being refined for PDT of H&N and other cancers, a
      parallel clinically relevant research area is the formulation of photosensitizers
      in nanovehicles that allow systemic administration yet preferential enhanced
      uptake in the tumor. This approach can render dual-selectivity of PDT, by
      harnessing both the drug and the light delivery within the tumor. To this end, we
      report on a cell-targeted nanomedicine approach for the photosensitizer silicon
      phthalocyanine-4 (Pc 4), by packaging it within polymeric micelles that are
      surface-decorated with GE11-peptides to promote enhanced cell-selective binding
      and receptor-mediated internalization in EGFR-overexpressing H&N cancer cells.
      Using fluorescence spectroscopy and confocal microscopy, we demonstrate in vitro
      that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in
      EGFR-overexpressing H&N SCC-15 cells. We further demonstrate that this enhanced
      Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT
      clonogenicity. Building on this in vitro data, we demonstrate that the EGFR
      targeted Pc 4-nanoformulation results in significant intratumoral drug uptake and
      subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice.
      Altogether our results show significant promise toward a cell-targeted
      photodynamic nanomedicine for effective treatment of H&N carcinomas.

PMID- 23531080
TI  - MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by
      targeting the key cell cycle regulator WEE1.
AB  - BACKGROUND: Neuroblastoma is responsible for 15% of all childhood cancer deaths.
      Despite advances in treatment and disease management, the overall 5-year survival
      rates remain poor in high-risk disease (25-40%). MiR-497 was previously
      identified by our laboratory as a member of a miRNA expression signature,
      predictive of neuroblastoma patient survival and has been reported as a tumor
      suppressor in a variety of other cancers. WEE1, a tyrosine kinase regulator of
      the cell cycle and predicted target of miR-497, has emerged as an oncogene in
      several cancer types and therefore represents an attractive potential target for
      novel therapy approaches in high-risk neuroblastoma. Our aim was to investigate
      the potential tumor suppressive role of miR-497 in high-risk neuroblastoma.
      METHODS: Expression levels of miR-497 and WEE1 in tissues and cells were
      determined using RT-PCR. The effect of miR-497 and siWEE1 on cell viability was
      evaluated using MTS assays, apoptosis levels were determined using FACS analysis
      of Annexin V/PI stained cells, and target protein expression was determined using
      western blot. Luciferase reporter plasmids were constructed to confirm direct
      targeting. Results were reported as mean+/-S.E.M and differences were tested for
      significance using 2-tailed Students t-test. RESULTS: We determined that miR-497
      expression was significantly lower in high-risk MYCN amplified (MNA) tumors and
      that low miR-497 expression was associated with worse EFS and OS in our cohort.
      Over-expression of miR-497 reduced cell viability and increased apoptosis in MNA
      cells. We identified WEE1 as a novel target for miR-497 in neuroblastoma.
      Furthermore, our analysis showed that high WEE1 levels are significantly
      associated with poor EFS and OS in neuroblastoma and that siRNA knockdown of WEE1
      in MNA cell lines results in significant levels of apoptosis, supporting an
      oncogenic role of WEE1 in neuroblastoma. Cisplatin (CDDP) treatment of both miR
      497 over-expressing cells and WEE1 inhibited cells, resulted in a significant
      increase in apoptosis in MNA cells, describing a synergistic effect and therefore
      a potential therapeutic for high-risk neuroblastoma. CONCLUSION: Our study's
      results are consistent with miR-497 being a candidate tumor suppressor in
      neuroblastoma, through the direct targeting of WEE1. These findings re-enforce
      the proposal of WEE1 as a therapeutic target in neuroblastoma.

PMID- 23531081
TI  - Changes in quality of life into adulthood after very preterm birth and/or very
      low birth weight in the Netherlands.
AB  - BACKGROUND: It is important to know the impact of Very Preterm (VP) birth or Very
      Low Birth Weight (VLBW). The purpose of this study is to evaluate changes in
      Health-Related Quality of Life (HRQoL) of adults born VP or with a VLBW, between
      age 19 and age 28. METHODS: The 1983 nationwide Dutch Project On Preterm and
      Small for gestational age infants (POPS) cohort of 1338 VP (gestational age <32
      weeks) or VLBW (<1500 g) infants, was contacted to complete online questionnaires
      at age 28. In total, 33.8% of eligible participants completed the Health
      Utilities Index (HUI3), the London Handicap Scale (LHS) and the WHOQoL-BREF.
      Multiple imputation was applied to correct for missing data and non-response.
      RESULTS: The mean HUI3 and LHS scores did not change significantly from age 19 to
      age 28. However, after multiple imputation, a significant, though not clinically
      relevant, increase of 0.02 on the overall HUI3 score was found. The mean HRQoL
      score measured with the HUI3 increased from 0.83 at age 19 to 0.85 at age 28. The
      lowest score on the WHOQoL was the psychological domain (74.4). CONCLUSIONS:
      Overall, no important changes in HRQoL between age 19 and age 28 were found in
      the POPS cohort. Psychological and emotional problems stand out, from which
      recommendation for interventions could be derived.

PMID- 23531082
TI  - Gating of a novel brain potential is associated with perceptual anomalies in
      bipolar disorder.
AB  - OBJECTIVES: Our laboratory recently identified the P85 gating ratio as a
      candidate biomarker for bipolar disorder. In order to evaluate the
      phenomenological significance of P85 gating, the current study examined reports
      of perceptual anomalies and their relationship to the P50 and P85 physiological
      measures of sensory gating. METHODS: Reports of perceptual anomalies on the
      Structured Clinical Interview to Assess Perceptual Anomalies were compared in
      patients meeting DSM-IV criteria for paranoid schizophrenia (n = 66),
      schizoaffective disorder (n = 45), or bipolar I disorder (n = 42), and controls
      (n = 56), as well as their relationship with P85 and P50 gating. RESULTS: The
      bipolar disorder group reported significantly more auditory, visual, and total
      anomalies than both the schizophrenia and control groups. The schizophrenia group
      also had more anomalies than the control group. Comparison of psychiatric
      subgroups revealed that the bipolar depressed, bipolar disorder with psychosis,
      and schizoaffective bipolar type groups reported the most anomalies compared to
      the other patient groups (bipolar disorder without psychosis, schizoaffective,
      bipolar manic). The total perceptual anomalies score and the P85 ratio
      significantly differentiated the bipolar disorder, schizoaffective, and paranoid
      schizophrenia groups from each other. CONCLUSIONS: These findings provide
      evidence of the phenomenological significance of P85. The results also yield
      further support not only for the P85 ratio, but also for increased reports of
      perceptual anomalies as possible markers for bipolar disorder.

PMID- 23531083
TI  - EcoTILLING in Beta vulgaris reveals polymorphisms in the FLC-like gene BvFL1 that
      are associated with annuality and winter hardiness.
AB  - BACKGROUND: Sugar beet (Beta vulgaris ssp. vulgaris L.) is an important crop for
      sugar and biomass production in temperate climate regions. Currently sugar beets
      are sown in spring and harvested in autumn. Autumn-sown sugar beets that are
      grown for a full year have been regarded as a cropping system to increase the
      productivity of sugar beet cultivation. However, for the development of these
      "winter beets" sufficient winter hardiness and a system for bolting control is
      needed. Both require a thorough understanding of the underlying genetics and its
      natural variation. RESULTS: We screened a diversity panel of 268 B. vulgaris
      accessions for three flowering time genes via EcoTILLING. This panel had been
      tested in the field for bolting behaviour and winter hardiness. EcoTILLING
      identified 20 silent SNPs and one non-synonymous SNP within the genes BTC1, BvFL1
      and BvFT1, resulting in 55 haplotypes. Further, we detected associations of
      nucleotide polymorphisms in BvFL1 with bolting before winter as well as winter
      hardiness. CONCLUSIONS: These data provide the first genetic indication for the
      function of the FLC homolog BvFL1 in beet. Further, it demonstrates for the first
      time that EcoTILLING is a powerful method for exploring genetic diversity and
      allele mining in B. vulgaris.

PMID- 23531084
TI  - The production and recognition of psychiatric original articles published in
      languages other than English.
AB  - BACKGROUND: Whereas the most influential journals in psychiatry are English
      language journals, periodicals published in other languages serve an important
      purpose for local communities of clinicians and researchers. This study aimed at
      analyzing the scientific production and the recognition of non-English general
      psychiatry journals. METHODS: In a cohort study, the 2009 volume of ten journals
      from Brazil (1), German language countries (5), France (2), Italy (1), and Poland
      (1) was searched for original articles. Patterns of citations to these articles
      during 2010 and 2011 as documented in Web of Science were analyzed. RESULTS: The
      journals published 199 original articles (range: 4-46), mostly observational
      studies. Half of the papers were cited in the following two years. There were 246
      citations received, or an average of 1.25 cites per article (range: 0.25-4.04).
      Many of these citations came from the local community, that is, from the same
      authors and journals. Citations by other periodicals and other authors accounted
      for 36% [95%-CI: 30%-42%], citations in English sources for 33% [28%-39%] of all
      quotations. There was considerable heterogeneity with regard to citations
      received among the ten journals investigated. CONCLUSION: Non-English language
      general psychiatry journals contribute substantially to the body of research.
      However, recognition, and in particular recognition by the international research
      community is moderate.

PMID- 23531085
TI  - Age-related differences in the cloacal microbiota of a wild bird species.
AB  - BACKGROUND: Gastrointestinal bacteria play a central role in the health of
      animals. The bacteria that individuals acquire as they age may therefore have
      profound consequences for their future fitness. However, changes in microbial
      community structure with host age remain poorly understood. We characterised the
      cloacal bacteria assemblages of chicks and adults in a natural population of
      black-legged kittiwakes (Rissa tridactyla), using molecular methods. RESULTS: We
      show that the kittiwake cloaca hosts a diverse assemblage of bacteria. A greater
      number of total bacterial OTUs (operational taxonomic units) were identified in
      chicks than adults, and chicks appeared to host a greater number of OTUs that
      were only isolated from single individuals. In contrast, the number of bacteria
      identified per individual was higher in adults than chicks, while older chicks
      hosted more OTUs than younger chicks. Finally, chicks and adults shared only
      seven OTUs, resulting in pronounced differences in microbial assemblages. This
      result is surprising given that adults regurgitate food to chicks and share the
      same nesting environment. CONCLUSIONS: Our findings suggest that chick
      gastrointestinal tracts are colonised by many transient species and that
      bacterial assemblages gradually transition to a more stable adult state.
      Phenotypic differences between chicks and adults may lead to these strong
      differences in bacterial communities. These data provide the framework for future
      studies targeting the causes and consequences of variation in bacterial
      assemblages in wild birds.

PMID- 23531086
TI  - Does school size affect interest for purchasing local foods in the midwest?
AB  - BACKGROUND: Due to the recent surge in environmental consciousness and the need
      to address childhood obesity, Farm to School programs have gained momentum. Even
      though Farm to School programs have increased in popularity, many schools still
      fail to take advantage of the benefits from such programs. School food service
      employees' lack of familiarity with the benefits of Farm to School programs or
      the means to overcome obstacles to implement such programs, along with school
      size, may represent key variables that serve to explain why more schools do not
      purchase more local foods for their schools. METHODS: This study used a
      convenience sampling methodology to gather information regarding food service
      employees' perceptions of the benefits and obstacles and their attitudes to
      purchasing and serving local foods in their schools. A self-administered
      questionnaire was used to collect data from school food service employees in
      southern Illinois. Data (n=151) were collected from 60 schools, representing 16
      counties during the month of December, 2009. RESULTS: Purchasers from large- and
      medium-size schools perceived the "ability to know product sources" as a greater
      benefit to purchasing local food and perceived "cost of food," "adequate volume,"
      "reliable supply of food quantity," "payment arrangement," and "packing material"
      as greater obstacles (p<0.05) compared to small schools. In addition, results
      indicated that food service employees were interested in receiving training to
      prepare and serve more local foods. CONCLUSIONS: Findings from this study
      indicate a need for continued education, development, and training to better
      prepare school food service purchasers in southern Illinois for how to buy more
      local foods to meet the 2020 legislation requiring schools to purchase at least
      10% locally.

PMID- 23531087
TI  - When the chimney is blocked: malignant renovascular hypertension after
      endovascular repair of abdominal aortic aneurysm.
AB  - BACKGROUND: The Chimney graft (CG) procedure is one of the novel modification
      techniques of the endovascular aneurysm repair (EVAR) surgery to treat suprarenal
      and juxtarenal abdominal aortic aneurysms. Other indications for the use of CG
      placement include thoracic and thoracoabdominal aneurysms with supraortic
      branches orifice involvement and cases of common iliac artery aneurysms with or
      without internal iliac artery involvement. The technique is used in patients who
      due to aortic-neck morphology and lack of adequate fixation and/or sealing zones
      are not eligible for standard EVAR. In this procedure, a parallel stent-graft is
      placed adjacent to the main body of the aortic endograft to maintain blood supply
      to renovisceral or supraortic branches, once the body of the aortic stent-graft
      is deployed. Symptomatic occlusions of the CG with novel renovascular
      hypertension were not described until now. CASE PRESENTATION: A-64-year-old male
      patient, presented with new-onset malignant hypertension, 13 months after an EVAR
      operation with CG placement to the left renal artery. The patient was on
      preventive clopidrogel therapy, which was withheld temporarily for several days,
      one month before presentation. Imaging studies revealed a novel form of
      iatrogenic renovascular hypertension, caused by occlusion of the CG. Any attempt
      to recanalize the covered stent or revascularize the left kidney was rejected and
      conservative treatment was chosen. Seven months after presentation, blood
      pressure was within normal ranges with little need for antihypertensive therapy.
      CONCLUSIONS: Physicians should be aware that the novel emerging techniques of
      EVAR to overcome the limitations of the aortic-neck anatomy may still adversely
      influence the renal outcome with potential development of new-onset hypertension.

PMID- 23531088
TI  - Variable Ki67 proliferative index in 65 cases of nodular fasciitis, compared with
      fibrosarcoma and fibromatosis.
AB  - Nodular fasciitis is the most common pseudosarcomatous lesion of soft tissue.
      Ki67 was considered as a useful marker for distinguishing some benign and
      malignant lesions. To study the usefulness of Ki67 in diagnosis of nodular
      fasciitis, the expression of Ki67 was examined by using immunostaining in 65
      nodular fasciitis specimens, 15 desmoid fibromatosis specimens and 20
      fibrosarcoma specimens. The results showed that there was a variable Ki67 index
      in all 65 cases of nodular fasciitis, and the mean labeling index was 23.71+/
      15.01%. In majority (70.77%) of all cases,the index was ranged from 10% to 50%,
      in 6.15% (4/65) of cases the higher Ki67 index (over 50%) could be seen. The Ki67
      proliferative index was closely related to duration of lesion, but not to age
      distribution, lesion size, sites of lesions and gender. Moreover, the mean
      proliferative index in desmoid fibromatosis and fibrosarcoma was 3.20+/-1.26% and
      26.15+/-3.30% respectively. The mean Ki67 index of nodular fasciitis was not
      significantly lower than fibrosarcoma, but higher than desmoid fibromatosis. The
      variable and high Ki67 index in nodular fasciitis may pose a diagnostic
      challenge. We should not misdiagnose nodular fasciitis as a sarcoma because of
      its high Ki67 index. The recurrence of nodular fasciitis is rare; and the utility
      of Ki67 immunostaining may be not suitable for recurrence assessment in nodular
      fasciitis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/4782335818876666.

PMID- 23531089
TI  - Comparison between two mobile pre-hospital care services for trauma patients.
AB  - OBJECTIVES: Pre-hospital care (PH) in Brazil is currently in the phase of
      implementation and expansion, and there are few studies on the impacts of this
      public health service. The purpose of this study is to assess the quality of care
      and severity of trauma among the population served, using trauma scores,
      attendance response times, and mortality rates. This work compares two pre
      hospital systems: the Mobile Emergency Care Service, or SAMU 192, and the Fire
      Brigade Group, or CB. METHOD: Descriptive study evaluating all patients
      transported by both systems in Catanduva, SP, admitted to a single hospital.
      RESULTS: 850 patients were included, most of whom were men (67.5%); the mean age
      was 38.5 +/- 18.5 years. Regarding the use of PH systems, most patients were
      transported by SAMU (62.1%). The trauma mechanisms involved motorcycle accidents
      in 32.7% of cases, transferred predominantly by SAMU, followed by falls (25.8%).
      Regarding the response time, CB showed the lowest rates. In relation to patient
      outcome, only 15.5% required hospitalization. The average score on the Glasgow
      Coma Scale was 14.7 +/- 1.3; average RTS was 7.7 +/- 0.7; ISS 3.8 +/- 5.9; and
      average TRISS 97.6 +/- 9.3. The data analysis showed no statistical differences
      in mortality between the groups studied (SAMU - 1.5%; CB - 2.5%). The trauma
      scores showed a higher severity of trauma among the fatal victims. CONCLUSION:
      Trauma victims are predominantly young and male; the trauma mechanism that
      accounted for the majority of PH cases was motorcycle accidents; CB responded
      more quickly than SAMU; and there was no statistical difference between the
      services of SAMU and CB in terms of severity of the trauma and mortality rates.

PMID- 23531090
TI  - Microsphere formation in a subtype of Creutzfeldt-Jakob disease with a V180I
      mutation and codon 129 MM polymorphism.

PMID- 23531091
TI  - Aromatically enhanced pear distillates from blanquilla and conference varieties
      using a packed column.
AB  - Pear distillates are generally produced from the Bartlett variety because of its
      rich aroma. In this study, a chemical and sensorial comparative examination of
      pear distillates from the three main varieties grown in Spain (Bartlett,
      Blanquilla, and Conference) using two distillation systems (copper Charentais
      alembic and packed column) was undertaken. Volatile compounds were identified by
      gas chromatography to differentiate the spirits according to pear variety and
      distillation method. The Bartlett distillates from both distillation systems
      possessed higher ethyl ester and acetate and lower cis-3-hexen-1-ol and 1-hexanol
      concentrations. Despite these differences, a sensory analysis panel could
      distinguish only the Bartlett alembic distillate from the alembic distillates of
      the other varieties. In contrast, the panel rated the packed-column distillates
      equally. Therefore, less aromatic pear varieties can be used to produce
      distillates with aromatic characteristics similar to those of the Bartlett
      variety if a suitable distillation process is used.

PMID- 23531092
TI  - Assessment of extent of apoptosis and DNA defragmentation in chilled semen of
      stallions during the breeding season.
AB  - The objective of the study was to assess apoptosis and DNA defragmentation in
      equine semen diluted and chilled to +4 degrees C. Semen was collected from nine
      fertile stallions, including four Arabian thoroughbreds and five coldbloods.
      Examinations were carried out immediately after semen collection (0) and at five
      storage times (24, 48, 72, 96 and 120 h). The basic semen evaluation was
      performed in terms of volume, sperm concentration, viable sperm percentage,
      progressive motility and morphology. Using flow cytometry, DNA defragmentation
      and cell membrane integrity of spermatozoa were determined. The results of basic
      tests did not demonstrate significant differences amongst stallions, except for
      progressive sperm motility, which was significantly higher (p < 0.05) in the
      semen of Arabian stallions. In the semen of the same stallions, a significant
      decrease in the percentage of alive spermatozoa was observed at 72, 96 and 120 h
      of storage, whereas a significant increase in the number of spermatozoa with DNA
      defragmentation was found after 24 h storage. In the semen of coldblood
      stallions, significantly reduced live spermatozoa percentage was observed at 96
      and 120 h, while increased DNA defragmentation was observed at 48 h. These
      findings demonstrated that the semen of Arabian stallions chilled to +4 degrees C
      retained original characteristics until 24 h of storage, whereas in coldbloods,
      these were preserved up to 48 h of storage. 

PMID- 23531093
TI  - Chronic venous leg ulcers are associated with high levels of metalloproteinases-9
      and neutrophil gelatinase-associated lipocalin.
AB  - Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix
      metalloproteinases (MMP) and neutrophil gelatinase-associated lipocalin (NGAL)
      could play a role in the healing process in patients with chronic venous ulcers.
      We evaluated the role of MMP-9 and NGAL in the healing process in venous
      ulceration. We performed an open-label, parallel groups, single clinical center
      study. Patients with chronic venous leg ulcers represented the test group (Group
      I), whereas patients without chronic ulcers represented the control group (Group
      II). In Group I plasma and wound fluid samples were collected at the time of
      admission, at the time of the surgery, and at the follow-up, while ulcer tissues
      were taken at the time of the surgery. In Group II, plasma and wound fluid were
      collected at admission and at the time of the surgery, whereas skin tissues were
      collected at the time of the surgery. Enzyme-linked immunosorbent assay test was
      used to evaluate the levels of MMP-9 and NGAL in plasma and wound fluid, whereas
      Western blot analysis was performed to estimate the expression of MMP-9 and NGAL
      in tissues. Enzyme-linked immunosorbent assay tests revealed significantly higher
      levels of MMP-9 and NGAL in both plasma and wound fluid of patients with ulcers
      compared to patients without ulcers (p < 0.01). Moreover, Western blot analysis
      documented an increased expression of MMP-9 and NGAL in biopsy tissue of patients
      with ulcers compared to patients without ulcers (p < 0.01). In conclusion MMP-9
      and NGAL may correlate with the clinical course of venous ulcers.

PMID- 23531094
TI  - Patients' use of self-monitored readings for managing everyday life with COPD: a
      qualitative study.
AB  - OBJECTIVE: Effects of self-monitoring depend on how patients engage with readings
      and how this engagement is used for managing chronic disease. This article
      reports on a study of how chronic obstructive pulmonary disease (COPD) patients
      made use of readings during 16 weeks of self-monitoring. PATIENTS AND METHODS:
      Semistructured interviews were conducted with 22 COPD patients three times each:
      at the beginning, halfway through, and after the monitoring device was collected.
      Spouses of nine interviewees were present during one or more interviews. The
      analysis of how patients used self-monitored readings was based on critical
      psychology. RESULTS: Patients used readings to monitor bodily condition, to judge
      whether and when to contact health professionals, to communicate with health
      professionals about health management, to revise planned activities, to engage
      close relatives, and to motivate exercise and other health behavior. Self
      monitoring can produce a sense of security as readings provide grounds for
      explaining symptoms and widen the scope of possibilities for taking action.
      Patients experienced readings as encouraging, reassuring, depressing, worrisome,
      and at times disturbing. A few patients involved themselves with readings in ways
      that are emotionally challenging and contrary to medical advice. Reasons for not
      making use of self-monitoring include good health or not regarding monitoring as
      relevant at the time. CONCLUSIONS: Results can qualify the support health
      professionals offer in relation to patients' self-monitoring and self-management.

PMID- 23531095
TI  - Feasibility and acceptance of a pharmacist-run tele-oncology service for
      chemotherapy-induced nausea and vomiting in ambulatory cancer patients.
AB  - BACKGROUND: The use of telemedicine for cancer patients is limited, particularly
      in Asia. These patients need to be monitored because more are being treated as
      outpatients, so that any treatment-related side effects can be managed. We
      assessed the feasibility and acceptance of a pharmacist-run tele-oncology service
      to monitor chemotherapy-induced nausea and vomiting (CINV) in ambulatory cancer
      patients. PATIENTS AND METHODS: A single-center, prospective study was conducted
      at a local cancer center. Patients' CINV symptoms were monitored through short
      message service (SMS) for 5 days post-chemotherapy. Feasibility was measured by
      patients' adherence to the service, patient satisfaction, and number of
      pharmacist interventions. Acceptance was measured by the accrual rate. RESULTS:
      The accrual rate was 37.6% (68/181 patients). Sixty patients (median age, 49.5
      years) completed the study. Overall adherence was 73.3%. The majority (90.0%)
      were comfortable with the duration of SMS monitoring, especially adherent
      patients (95.5% versus 75.0%, p=0.038). Over half (61.7%) found the SMS advice
      useful. Twenty-two intervention calls were made by pharmacists for uncontrolled
      CINV. CONCLUSIONS: A pharmacist-run tele-oncology service for real-time
      monitoring of CINV is feasible in ambulatory cancer patients. Incorporating the
      monitoring of other side effects will enhance its value and acceptance by
      patients for post-chemotherapy symptom management.

PMID- 23531096
TI  - Incidence rates and risk factors of bipolar disorder in the general population: a
      population-based cohort study.
AB  - OBJECTIVE: To estimate the incidence rates (IRs) of bipolar I and bipolar II
      disorders in the general population according to sociodemographic population
      characteristics. METHODS: A cohort study (during the years 1996-2007) was
      conducted in a general practitioners research database with a longitudinal
      electronic record of 800000 patients throughout the Netherlands [the Integrated
      Primary Care Information (IPCI) database]. Cases of bipolar disorder were
      identified and classified by systematic review of medical records. Age- and
      gender-specific IRs were calculated per calendar year, degree of urbanization,
      and degree of deprivation. RESULTS: The overall IR of bipolar disorder was
      0.70/10000 person-years (PY) [95% confidence interval (CI): 0.57-0.83]; the IR of
      bipolar I disorder was 0.43/10000 PY (95% CI: 0.34-0.55) and the IR of bipolar II
      disorder was 0.19/10000 PY (95% CI: 0.13-0.27). Two peaks in the age at onset of
      the disorder were noticed: one in early adulthood (15-24 years; 0.68/10000 PY)
      and a larger peak in later life (45-54 years; 1.2/10000 PY). In bipolar II
      disorder, only one peak, in the 45-54 year age category (IR 0.42/10000 PY), was
      found. The IRs of bipolar disorder were significantly higher in deprived areas.
      Similar rates were found for men compared to women and in urban compared to rural
      areas. No association was found between the onset of first (hypo)manic episode
      and month or season of birth. CONCLUSIONS: We found two peaks in the age at onset
      of bipolar disorder, one in early adulthood and one in later life, the former
      consisting mainly of bipolar I disorder subjects. The incidence of bipolar
      disorder is higher in deprived areas. The onset of bipolar disorder is not
      associated with gender, urbanization, or month or season of birth.

PMID- 23531097
TI  - Persistent genital tract HIV-1 RNA shedding after change in treatment regimens in
      antiretroviral-experienced women with detectable plasma viral load.
AB  - OBJECTIVE: To longitudinally assess the association between plasma viral load
      (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1
      infected women changing highly active antiretroviral therapy (HAART) because of
      detectable PVL on current treatment. METHODS: Women were eligible for the study
      if they had detectable PVL (defined as two consecutive samples with PVL>1000
      copies/mL) and intended to change their current HAART regimen at the time of
      enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3
      years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the
      association with PVL. RESULTS: Sixteen women were followed for a median of 11
      visits contributing a total of 205 study visits. At study enrollment, all had
      detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to
      a new HAART regimen with >=3 active antiretroviral drugs. The probability of
      having detectable PVL >=30 days after changing HAART was 0.56 (95% CI: 0.37 to
      0.74). Fourteen women (88%) had detectable PVL on a follow-up visit >=30 or 60
      days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a
      follow-up visit >=30 or 60 days after changing HAART. When PVL was undetectable,
      GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding
      occurred at 47% of visits. CONCLUSIONS: Some treatment-experienced HIV-infected
      women continue to have detectable virus in both the plasma and GT following a
      change in HAART, highlighting the difficulty of viral suppression in this patient
      population.

PMID- 23531098
TI  - Gender differences in colon cancer treatment.
AB  - Abstract Background: Despite women suffering a disproportionate burden of colon
      cancer mortality, few studies have examined gender differences in evidence-based
      treatment, especially in poorer states like Alabama. OBJECTIVE: To describe colon
      cancer treatment in older patients diagnosed in Alabama by gender. METHODS: Colon
      cancer patients 65 years and older diagnosed in 2000-2002 were identified from
      the Alabama Statewide Cancer Registry (N=1785). Treatment was identified from
      Medicare claims for 1999-2003. Outcomes were (1) receipt of surgery and adjuvant
      5-fluorouracil chemotherapy (5FU) and (2) 5FU treatment duration (0-4, 5-7, and
      >7 months). Generalized Estimating Equation (GEE) models were used to determine
      significant gender differences, adjusting for clustering at the reporting
      hospital level, and controlling for race, age, stage, comorbid conditions, census
      tract-level socioeconomic variables, and adverse chemotherapy effects (when
      analyzing 5FU duration). RESULTS: Overall, 93.9% of the patients received
      surgery. Of stage II-III patients undergoing surgery, 60.4% stage III and 25.6%
      stage II patients received 5FU. Compared with men, women were more likely to have
      surgery (95.5% vs. 92.2%, p=0.003), less likely to have 5FU (38.6% vs. 45.2%,
      p=0.02), and more likely to have 0-4 months of 5FU (32.9% vs. 24.9%, p=0.05).
      Gender differences were significant for having chemotherapy (adjusted odds ratio
      [aOR] 0.78, confidence interval [CI] 0.61-1.00, p=0.049), but not for having 0-4
      months of 5FU when adjusting for adverse effects (aOR 1.36, CI 0.95-1.94,
      p=0.09). CONCLUSIONS: In Alabama, some gender differences in stage-specific colon
      cancer treatment are worth further scrutiny.

PMID- 23531099
TI  - Screening low-income women of reproductive age for cardiovascular disease risk
      factors.
AB  - Abstract Background: Identifying and treating chronic diseases, their precursors,
      and other cardiovascular disease (CVD) risk factors during family planning visits
      may improve long-term health and reproductive outcomes among low-income women. A
      cross-sectional study design was used to describe the prevalence of chronic
      diseases (hypertension, high cholesterol, and diabetes), their precursors (pre
      hypertension, borderline high cholesterol, and pre-diabetes), and related CVD
      risk factors (such as obesity, smoking, and physical inactivity) among low-income
      women of reproductive age. METHODS: Prevalence of chronic diseases, their
      precursors, and related CVD risk factors were assessed for 462 out of 859 (53.8%)
      female family planning patients, ages 18-44 years, who attended a Title X clinic
      in eastern North Carolina during 2011 and 2012 and consented to participate. Data
      were obtained from clinical measurements, blood test results, and questionnaire.
      Differences in distribution of demographic and health care characteristics and
      CVD risk factors by presence of prehypertension and pre-diabetes were assessed by
      Pearson chi-square tests. RESULTS: The prevalence of hypertension was 12%, high
      cholesterol 16%, and diabetes 3%. Nearly two-thirds of women with hypertension
      were newly diagnosed (62%) as were 75% of women with diabetes. The prevalence of
      pre-hypertension was 35%, pre-diabetes 31%, obesity 41%, smoking 32%, and
      physical inactivity 42%. The majority of participants (87%) had one or more
      chronic disease or related cardiovascular disease risk factor. CONCLUSIONS: CVD
      screening during family planning visits can identify significant numbers of women
      at risk for poor pregnancy outcomes and future chronic disease and can provide
      prevention opportunities if effective interventions are available and acceptable
      to this population.

PMID- 23531100
TI  - Gene expression analysis reveals marked differences in the transcriptome of
      infantile hemangioma endothelial cells compared to normal dermal microvascular
      endothelial cells.
AB  - BACKGROUND: Infantile hemangiomas are benign vascular tumors primarily found on
      the skin in 10% of the pediatric population. The etiology of this disease is
      largely unknown and while large scale genomic studies have examined the
      transcriptomes of infantile hemangioma tumors as a whole, no study to date has
      compared the global gene expression profiles of pure infantile hemangioma
      endothelial cells (HEMECs) to that of normal human dermal microvascular
      endothelial cells (HDMVECs). METHODS: To shed light on the molecular differences
      between these normal and aberrant dermal endothelial cell types, we performed
      whole genome microarray analysis on purified cultures of HEMECs and HDMVECs. We
      then utilized qPCR and immunohistochemistry to confirm our microarray results.
      RESULTS: Our array analysis identified 125 genes whose expression was upregulated
      and 104 genes whose expression was downregulated by greater than two fold in
      HEMECs compared to HDMVECs. Bioinformatics analysis revealed three major
      classifications of gene functions that were altered in HEMECs including cell
      adhesion, cell cycle, and arachidonic acid production. Several of these genes
      have been reported to be critical regulators and/or mutated in cancer, vascular
      tumors, and vascular malformations. We confirmed the expression of a subset of
      these differentially expressed genes (ANGPT2, ANTXR1, SMARCE1, RGS5, CTAG2,
      LTBP2, CLDN11, and KISS1) using qPCR and utilized immunohistochemistry on a panel
      of paraffin embedded infantile hemangioma tumor tissues to demonstrate that the
      cancer/testis antigen CTAG2 is highly abundant in vessel-dense proliferating
      infantile hemangiomas and with significantly reduced levels during tumor
      involution as vascular density decreases. CONCLUSION: Our data reveal that the
      transcriptome of HEMECs is reflective of a pro-proliferative cell type with
      altered adhesive characteristics. Moveover, HEMECs show altered expression of
      many genes that are important in the progression and prognosis of metastatic
      cancers.

PMID- 23531102
TI  - Local public health response to vaccine-associated measles: case report.
AB  - BACKGROUND: The most appropriate public health approach to vaccine-associated
      measles in immunocompromised patients is unknown, mainly because these cases are
      rare and transmission of vaccine-associated measles has not been previously
      documented. In this case report, we describe Peel Public Health's response to a
      vaccine-associated measles case in an immunocompromised child in Ontario, Canada.
      CASE PRESENTATION: A five-year-old Canadian-born boy with a history of a
      hematopoetic stem cell transplant three years previously received live attenuated
      measles, mumps, and rubella (MMR) vaccine. Over the subsequent 7 to 14 days, he
      developed an illness clinically consistent with measles. There was no travel
      history or other measles exposure. Serology and polymerase chain reaction (PCR)
      testing confirmed acute measles infection. Following discussion with pediatric
      infectious diseases specialists, but prior to the availability of virus
      sequencing, it was felt that this case was most likely due to vaccine strain.
      Although no microbiologically confirmed secondary cases of vaccine-associated
      measles have been previously described, we sent notification letters to advise
      all contacts of measles symptoms since the likelihood of transmission from an
      immunocompromised patient was low, but theoretically possible. We decided to
      stratify contacts into immune competent and compromised and to deal with the
      latter group conservatively by excluding them as if they were exposed to wild
      type measles because the risk of transmission of disease in this population,
      while presumably very low, is unknown. However, no contacts self-identified as
      immunocompromised and there were no secondary cases. Subsequent genotyping
      confirmed that this case was caused by vaccine strain measles virus. CONCLUSION:
      The public health approach to contact tracing and exclusions for vaccine
      associated measles in immunocompromised patients is unclear. The rarity of
      secondary cases provides further evidence that the risk to the general public is
      likely extremely low. Although the risk appears negligible, exclusion and
      administration of immune globulin may be considered for susceptible,
      immunocompromised contacts of cases of vaccine-associated measles in
      immunocompromised patients.

PMID- 23531101
TI  - Physiological effects of oral glucosamine on joint health: current status and
      consensus on future research priorities.
AB  - The aim of this paper was to provide an overview of the current knowledge and
      understanding of the potential beneficial physiological effects of glucosamine
      (GlcN) on joint health. The objective was to reach a consensus on four critical
      questions and to provide recommendations for future research priorities. To this
      end, nine scientists from Europe and the United States were selected according to
      their expertise in this particular field and were invited to participate in the
      Hohenheim conference held in August 2011. Each expert was asked to address a
      question that had previously been posed by the chairman of the conference. Based
      on a systematic review of the literature and the collection of recent data, the
      experts documented the effects of GlcN on cartilage ageing, metabolic/kinetic and
      maintenance of joint health as well as reduction of risk of OA development. After
      extensive debate and discussion the expert panel addressed each question and a
      general consensus statement was developed, agreeing on the current state-of-the
      art and future areas for basic and clinical studies. This paper summarizes the
      available evidence for beneficial effects of GlcN on joint health and proposes
      new insight into the design of future clinical trials aimed at identifying
      beneficial physiological effect of GlcN on joint tissues.

PMID- 23531103
TI  - Association of BDNF and BMPR1A with clinicopathologic parameters in benign and
      malignant gallbladder lesions.
AB  - BACKGROUND: Neurotrophic factors such as brain derived neurotrophic factor (BDNF)
      are synthesized in a variety of neural and non-neuronal cell types and regulate
      survival, proliferation and apoptosis. In addition, bone morphogenetic proteins
      (BMPs) inhibit the proliferation of pulmonary large carcinoma cells bone
      morphogenetic protein receptor, type IA (BMPR1A). Little is known about the
      expression of BDNF or BMPR1A in malignant gall bladder lesions. This study was to
      evaluate BDNF and BMPR1A expression and evaluate the clinicopathological
      significance in benign and malignant lesions of the gallbladder. METHODS: The
      BDNF and BMPR1A expression of gallbladder adenocarcinoma, peritumoral tissues,
      adenoma, polyp and chronic cholecystitis were Immunohistochemically determined.
      RESULTS: BDNF expression was significantly higher in gallbladder adenocarcinoma
      than in peritumoral tissues, adenoma, polyps and chronic cholecystitis samples.
      However, BMPR1A expression was significantly lower in gallbladder adenocarcinoma
      than in peritumoral tissues, adenomas, polyps and chronic cholecystitis tissues.
      The specimens with increased expression of BDNF in the benign lesions exhibited
      moderate- or severe-dysplasia of gallbladder epithelium. BDNF expression was
      significantly lower in well-differentiated adenocarcinomas with maximum tumor
      diameter <2 cm, no metastasis to lymph nodes, and no invasion of regional tissues
      compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2
      cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder
      adenocarcinoma. BMPR1A expression were significantly higher in the well
      differentiated adenocarcinoma with maximal tumor diameter <2 cm, no metastasis of
      lymph node, and no invasion of regional tissues compared to poorly-differentiated
      adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and
      invasiveness of regional tissues in gallbladder. Univariate Kaplan-Meier analysis
      indicated increased expression of BDNF or decreased expression of BMPR1A was
      associated with decreased disease specific survival (DSS) rates. Similarly,
      multivariate Cox regression analysis showed increased expression of BDNF or
      decreased expression of BMPR1A are independent predictors of poor DSS rates in
      gallbladder adenocarcinoma. CONCLUSIONS: In gallbladder malignancies, the
      increased expression of BDNF and decreased expression of BMPR1A were associated
      with increased risk of metastasis, regional invasion and mortality. They might
      serve as novel indicators of gallbladder adenocarcinoma outcomes, which may prove
      valuable for the development of personalized therapeutic paradigms.

PMID- 23531104
TI  - Histone modification via rapid cleavage of C4'-oxidized abasic sites in
      nucleosome core particles.
AB  - The C4'-oxidized abasic site is produced in DNA by a variety of oxidizing agents,
      including potent cytotoxic antitumor agents. Independent generation of this
      alkali-labile lesion at defined positions within nucleosome core particles
      reveals that the histone proteins increase strand scission between 130- and 550
      fold. Strand scission proceeds via a Schiff base intermediate, but the DNA
      protein cross-links are unstable. The oxidized abasic site is removed in its
      entirety from the DNA and transferred to the lysine-rich tail region of the
      proximal histone protein in the form of a lactam. The modification is distributed
      over several residues within the amino-terminal tail of the proximal histone.
      Transfer of DNA damage to histones could affect gene regulation.

PMID- 23531105
TI  - Rosiglitazone and bezafibrate modulate gene expression in a rat model of non
      alcoholic fatty liver disease--a historical prospective.
AB  - BACKGROUND: Genetic factors implicated in the pathogenesis of non-alcoholic fatty
      liver disease are poorly understood. Our aim was to characterize three genes
      involved in a rat model of non-alcoholic fatty liver disease and investigate the
      effect of rosiglitazone and bezafibrate. METHOD: Five rats were fed a chow diet
      (controls) and 18 a fructose-enriched diet (FED) for 5 weeks: 6 were administered
      rosiglitazone and 6 bezafibrate during the last 2 weeks and 6 were not treated at
      all. Livers were examined by reverse transcription-PCR for the genes encoding
      peroxisome proliferator-activated receptors (PPAR), PPAR-alpha, PPAR-gamma, and
      Mn superoxide dismutase2 (Mn SOD2). Western blot was used for proteins levels.
      RESULT: The FED rats showed a decrease in mRNA of MnSOD2, PPAR-alpha, and PPAR
      gamma (3, 3.5 fold, and 27%, respectively) (p<0.05). The 3 genes normalized in
      response to rosiglitazone and bezafibrate. The proteins of MnSOD2, PPAR-alpha and
      PPAR-gamma in the FED rats decreased (2.5, 2, and 2.2, respectively) (p<0.05).
      Following administration of rosiglitazone, proteins of MnSOD2, PPAR-alpha and
      PPAR-gamma in the FED rats increased (reaching 1.5-fold, a 20% increase and
      normalization, respectively), (p<0.05). Administration of bezafibrate to the FED
      rats restored the proteins of 3 genes to baseline. CONCLUSION: A consistent
      reduction in hepatic expression of MnSOD2, PPAR-alpha and PPAR-gamma in the FED
      rats compared with controls was observed. Administration of either rosiglitazone
      or bezafibrate to the FED rats restored these genes to a pre-morbid state.

PMID- 23531106
TI  - Modelling metabolic CO2 evolution--a fresh perspective on respiration.
AB  - Respiration is a major contributor to net exchange of CO2 between plants and the
      atmosphere and thus an important aspect of the vegetation component of global
      climate change models. However, a mechanistic model of respiration is lacking,
      and so here we explore the potential for flux balance analysis (FBA) to predict
      cellular CO2 evolution rates. Metabolic flux analysis reveals that respiration is
      not always the dominant source of CO2, and that metabolic processes such as the
      oxidative pentose phosphate pathway (OPPP) and lipid synthesis can be
      quantitatively important. Moreover, there is considerable variation in the
      metabolic origin of evolved CO2 between tissues, species and conditions.
      Comparison of FBA-predicted CO2 evolution profiles with those determined from
      flux measurements reveals that FBA is able to predict the metabolic origin of
      evolved CO2 in different tissues/species and under different conditions. However,
      FBA is poor at predicting flux through certain metabolic processes such as the
      OPPP and we identify the way in which maintenance costs are accounted for as a
      major area of improvement for future FBA studies. We conclude that FBA, in its
      standard form, can be used to predict CO2 evolution in a range of plant tissues
      and in response to environment.

PMID- 23531107
TI  - Preventing interfacial recombination in colloidal quantum dot solar cells by
      doping the metal oxide.
AB  - Recent research has pushed the efficiency of colloidal quantum dot solar cells
      toward a level that spurs commercial interest. Quantum dot/metal oxide bilayers
      form the most efficient colloidal quantum dot solar cells, and most studies have
      advanced the understanding of the quantum dot component. We study the interfacial
      recombination process in depleted heterojunction colloidal quantum dot (QD) solar
      cells formed with ZnO as the oxide by varying (i) the carrier concentration of
      the ZnO layer and (ii) the density of intragap recombination sites in the QD
      layer. We find that the open-circuit voltage and efficiency of PbS QD/ZnO devices
      can be improved by 50% upon doping of the ZnO with nitrogen to reduce its carrier
      concentration. In contrast, doping the ZnO did not change the performance of PbSe
      QD/ZnO solar cells. We use X-ray photoemission spectroscopy, ultraviolet
      photoemission spectroscopy, transient photovoltage decay measurements, transient
      absorption spectroscopy, and intensity-dependent photocurrent measurements to
      investigate the origin of this effect. We find a significant density of intragap
      states within the band gap of the PbS quantum dots. These states facilitate
      recombination at the PbS/ZnO interface, which can be suppressed by reducing the
      density of occupied states in the ZnO. For the PbSe QD/ZnO solar cells, where
      fewer intragap states are observed in the quantum dots, the interfacial
      recombination channel does not limit device performance. Our study sheds light on
      the mechanisms of interfacial recombination in colloidal quantum dot solar cells
      and emphasizes the influence of quantum dot intragap states and metal oxide
      properties on this loss pathway.

PMID- 23531108
TI  - Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.
AB  - Economic evaluations of health interventions pose a particular challenge for
      reporting. There is also a need to consolidate and update existing guidelines and
      promote their use in a user friendly manner. The Consolidated Health Economic
      Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate
      and update previous health economic evaluation guidelines efforts into one
      current, useful reporting guidance. The primary audiences for the CHEERS
      statement are researchers reporting economic evaluations and the editors and peer
      reviewers assessing them for publication.The need for new reporting guidance was
      identified by a survey of medical editors. A list of possible items based on a
      systematic review was created. A two round, modified Delphi panel consisting of
      representatives from academia, clinical practice, industry, government, and the
      editorial community was conducted. Out of 44 candidate items, 24 items and
      accompanying recommendations were developed. The recommendations are contained in
      a user friendly, 24 item checklist. A copy of the statement, accompanying
      checklist, and this report can be found on the ISPOR Health Economic Evaluations
      Publication Guidelines Task Force website
      (http://www.ispor.org/TaskForces/EconomicPubGuidelines.asp).We hope CHEERS will
      lead to better reporting, and ultimately, better health decisions. To facilitate
      dissemination and uptake, the CHEERS statement is being co-published across 10
      health economics and medical journals. We encourage other journals and groups, to
      endorse CHEERS. The author team plans to review the checklist for an update in
      five years.

PMID- 23531109
TI  - Meeting report: The future of preclinical mouse models in melanoma treatment is
      now.

PMID- 23531110
TI  - Novel targeted therapies to overcome trastuzumab resistance in HER2
      overexpressing metastatic breast cancer.
AB  - Overexpression of the human epidermal growth factor receptor 2 (HER2) is
      identified in approximately 25- 30% of breast cancers and indicates a poor
      prognosis. Trastuzumab, the anti-HER2 monoclonal antibody (mAb), has shown
      significant clinical effects selectively in HER2-overexpressing metastatic breast
      cancer (MBC) with improved overall survival and reduced recurrent risk. However,
      there is an urgent need to develop new strategies to overcome innate and acquired
      trastuzumab resistance, which has increasingly occurred. Recently, an increased
      understanding of mechanisms of trastuzumab resistance significantly promotes the
      development of novel targeted therapies for trastuzumab refractory disease. It is
      believed that aberrant activations of several signaling pathways involving the
      human epidermal growth factor receptor (EGFR/HER) family, phosphoinositide 3
      kinase/Akt (PI3K/Akt) pathway, and vascular endothelial growth factor (VEGF)
      family, contribute to the development of trastuzumab resistance. Novel agents
      that target these relevant signal pathways provide some potential solutions, such
      as tyrosine kinase inhibitors (TKIs) and mAbs. HER2 is also recognized as an
      immunotherapeutic target. The failure to induce immune-mediated antitumor
      response is another important reason for trastuzumab resistance. Strategies to
      boost T cell-mediated immune responses specific to HER2 including HER2 vaccines
      and bispecific antibodies (bsAbs) could be developed as a promising way to
      prevent relapse or combat trastuzumab resistance. In this review, the emerging
      data from preclinical and clinical studies related to these novel therapies will
      be discussed.

PMID- 23531111
TI  - Hypoxia-inducible factor: a potential therapeutic target for rheumatoid
      arthritis.
AB  - The hypoxic microenvironment is a clinicopathological characteristic of many
      diseases, such as rheumatoid arthritis (RA). As a transcription factor activating
      the gene expression involved in processes such as cell metabolism and
      angiogenesis, hypoxia-inducible factor (HIF) has a central function in adaption
      to altered oxygen tension and even contributes to the progression of related
      diseases. In RA, HIF induces angiogenesis, cell migration, and cartilage
      destruction, inhibits the apoptosis of synovial cells and inflammatory cells and
      initiates glycolysis for energy supply by upregulating specific protein levels.
      HIF expression in RA can be regulated in both oxygen-dependent and independent
      fashions, leading to the aggravation of this disease. Therefore, HIF is one of
      the vital RA mediators. Based on the application of HIF-targeted drug research
      and development in tumors, HIF is a potential therapeutic target for treating RA.

PMID- 23531112
TI  - Aromatherapy and the central nerve system (CNS): therapeutic mechanism and its
      associated genes.
AB  - Molecular medical research on aromatherapy has been steadily increasing for use
      as an adjuvant therapy in managing psychiatric disorders and to examine its
      therapeutic mechanisms. Most studies, as well as clinically applied experience,
      have indicated that various essential oils, such as lavender, lemon and bergamot
      can help to relieve stress, anxiety, depression and other mood disorders. Most
      notably, inhalation of essential oils can communicate signals to the olfactory
      system and stimulate the brain to exert neurotransmitters (e.g. serotonin and
      dopamine) thereby further regulating mood. However, little research has been done
      on the molecular mechanisms underlying these effects, thus their mechanism of
      action remains ambiguous. Several hypotheses have been proposed regarding the
      therapeutic mechanism of depression. These have mainly centered on possible
      deficiencies in monoamines, neurotrophins, the neuroendocrine system, c-AMP,
      cation channels as well as neuroimmune interactions and epigenetics, however the
      precise mechanism or mechanisms related to depression have yet to be elucidated.
      In the current study, the effectiveness of aromatherapy for alleviating
      psychiatric disorders was examined using data collected from previously published
      studies and our unpublished data. A possible signaling pathway from olfactory
      system to the central nerve system and the associated key molecular elements of
      aromatherapy are also proposed. 

PMID- 23531113
TI  - Omega-3 fatty acids as pharmacotherapeutics in psoriasis: current status and
      scope of nanomedicine in its effective delivery.
AB  - Psoriasis is a multifactorial autoimmune skin disorder based on irregularities of
      the T- cell function. The abnormal keratinocyte hyper proliferation in psoriasis
      arises due to the activation of T-cells which produces rich amount of arachidonic
      acid leads to generation of various proinflammatory mediators like PGs, LTs,
      cytokines and adhesion molecules via MAPK/AP-1, EARK1/2 and protein kinase-C
      (PKCs) activation pathways. Incorporation of naturally occuring bioactives like,
      omega (omega)-3 fatty acids (i.e., EPA and DHA) in a dose dependent manner
      results in inhibition of various pro-inflammatory mediators and metabolization of
      EPA and DHA leads to dampening of inflammation and higher resolution of the skin
      abnromalities. These all due to the promotion of the synthesis of omega-3 PUFA
      derived lipid mediators viz namely resolvins and protectins. These have been
      widely used alone or in combination with other drugs in the treatment of
      psoriasis. Despite of their meritorious visages, the use of these bioactives is
      associated with several hiccups like higher unstability and vulnerable to
      degradation due to lipid peroxidation, poor and incosistent bioavilability by
      oral and topical administration. The potential use of nanomedicines in the
      delivery of such bioactives has gained wider attention owing to their promising
      bioavailability enhancement characteristics, improved stability and better
      efficacy. The present review gives an extensive account on omega-3 fatty acids
      (EPA and DHA) starting from seedling to apex, including biosynthesis,
      metabolites, and its mechanism of action in psoriasis. Moreover, barriers in the
      effective delivery of omega-3 fatty acids and how nanomedicines can be fit in the
      scope of its therapeutic delivery in psoriasis have also been addressed. Despite
      numerous advantages, application of EPA-DHA as omega-3 fatty acids therapeutics
      in the management of psoriasis are still at an initial stage. Nanomedicines
      approach to achieve high bioavailable delivery with safety and stability of omega
      3 fatty acids showing the promising area for the future in psoriasis management.

PMID- 23531114
TI  - Niosomes encapsulating Ibuprofen-cyclodextrin complexes: preparation and
      characterization.
AB  - A new delivery system based on ibuprofen-beta-cyclodextrin (betaCd) complexation
      and its loading into non-ionic surfactant vesicles (NSVs) was developed to
      improve ibuprofen therapeutic efficacy in topical formulations. The proposed
      strategy exploits the well known solubilizing and stabilizing properties of
      cyclodextrins together with the high tolerability and percutaneous absorption
      enhancing properties of NSVs. The complexing capacity of Cds in the presence of
      Ibuprofen in aqueous solution was evaluated by means of phase solubility studies.
      The technique used to obtain solid ibuprofen-betaCd complexes was the co
      lyophilization method. The influence of the preparation method on the
      physicochemical properties of the final product was evaluated by means of Fourier
      Transform Infrared Spectroscopy and Differential scanning calorimetry studies.
      Ibuprofen-betaCd complexes were included in Tween 20/Cholesterol vesicles and
      characterized in terms of size, zeta (zeta)-potential, stability, drug entrapment
      efficiency and drug release. The best ibuprofen-betaCd-NSV system exhibited in
      vitro drug permeation properties significantly improved with respect to those of
      the plain drug suspension. 

PMID- 23531115
TI  - Serotonergic drugs for depression and beyond.
AB  - The current generation of antidepressant drugs acts predominantly by targeting
      the serotonin transporter (SERT). The original trend to do this selectively
      (e.g., with SSRIs or selective serotonin reuptake inhibitors) has given way to
      combining various additional pharmacologic mechanisms with SERT inhibition,
      including dual actions by single drugs (e.g., SNRIs or serotonin norepinephrine
      reuptake inhibitors), or by augmenting SSRIs with a second drug of a different
      mechanism (e.g., bupropion with dopamine and norepinephrine reuptake inhibition;
      trazodone with 5HT2A antagonism; mirtazapine with 5HT2A/5HT2C/5HT3/alpha2
      antagonism; buspirone or some atypical antipsychotics with 5HT1A partial agonism;
      other atypical antipsychotics with 5HT2C/5HT7 antagonism and other mechanisms).
      Novel drugs in development include those that combine multiple simultaneous
      pharmacologic mechanisms in addition to SERT inhibition within the same molecule,
      such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple
      reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition
      with SERT inhibition), and vortioxetine, a multimodal antidepressant combining
      actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7
      antagonism), at the ion channel mode (5HT3 antagonism) as well as the
      neurotransmitter transporter mode (SERT inhibition). These various strategies
      that build upon SERT inhibition provide promise for novel therapeutic approaches
      to depression, including the possibility of targeting residual symptoms not well
      treated by SERT inhibition alone, and reducing side effects, such as sexual
      dysfunction.

PMID- 23531116
TI  - Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics:
      rationales, controversies, clinical experience.
AB  - Nicotinamide adenine dinucleotide (NAD+) biosynthesis from nicotinamide is used
      by mammalian cells to replenish their NAD+ stores and to avoid unwanted
      nicotinamide accumulation. Pharmacological inhibition of nicotinamide
      phosphoribosyltransferase (NAMPT), the key enzyme in this biosynthetic pathway,
      almost invariably leads to intracellular NAD+ depletion and, when protracted, to
      ATP shortage and cell demise. Cancer cells and activated immune cells express
      high levels of NAMPT and are highly susceptible to NAMPT inhibitors, as shown by
      the activity of these agents in models of malignant and inflammatory disorders.
      As the spectrum of conditions which could benefit from pharmacological NAMPT
      inhibition becomes broader, the mechanisms accounting for their activity are also
      eventually becoming apparent, including the induction of autophagy and the
      impairment of Ca2+--and NF-kappaB-dependent signaling. Here, we discuss the
      rationales for exploiting NAMPT inhibitors in cancer and inflammatory diseases
      and provide an overview of the preclinical and clinical studies in which these
      agents have been evaluated.

PMID- 23531117
TI  - One-year randomized study of the endometrial safety and bleeding pattern of 0.25
      mg drospirenone/0.5 mg 17beta-estradiol in postmenopausal women.
AB  - OBJECTIVES: To investigate the long-term endometrial safety and bleeding pattern
      of the 0.25 mg drospirenone/0.5 mg 17beta-estradiol (DRSP/E2) dose combination
      compared with 0.5 mg norethisterone acetate (NETA)/1.0 mg E2, in postmenopausal
      women. METHODS: A total of 662 postmenopausal women aged between 40 and 65 years
      with an indication for hormone therapy verified by the investigator were
      randomized to participate in this 1-year, double-blind, active comparator
      controlled study. The primary efficacy variable was the proportion of women with
      an endometrial biopsy assessment of 'hyperplasia or worse' at any time during or
      after 13 cycles of treatment. RESULTS: No evaluable women in the DRSP/E2 or
      NETA/E2 groups had an endometrial biopsy result of 'hyperplasia or worse'. The
      incidence of amenorrhea was higher in the DRSP/E2 group than the NETA/E2 group
      during months 1-3 (69.0% vs. 56.0%), with comparable amenorrhea rates of
      approximately 80% during months 10-12. Improvements in menopausal symptoms
      (exploratory efficacy variables) were similar in the two groups, while there were
      fewer women with treatment-related adverse events (18.4% vs. 25.6%) or adverse
      events leading to discontinuation of study drug (8.4% vs. 15.1%) in the DRSP/E2
      group than the NETA/E2 group. There were no treatment-related thromboembolic or
      cardiovascular events in the DRSP/E2 group vs. two events in the NETA/E2 group.
      CONCLUSIONS: The low-dose, 0.25 mg DRSP/0.5 mg E2 dose combination met the
      criteria for endometrial safety and demonstrated a favorable risk/benefit profile
      in this 1-year, double-blind, randomized study of postmenopausal women.

PMID- 23531118
TI  - Alogliptin versus glipizide monotherapy in elderly type 2 diabetes mellitus
      patients with mild hyperglycaemia: a prospective, double-blind, randomized, 1
      year study.
AB  - AIM: To prospectively evaluate the efficacy and safety of alogliptin versus
      glipizide in elderly patients with type 2 diabetes mellitus (T2DM) over 1 year of
      treatment. METHODS: This was a randomized, double-blind, active-controlled study
      of elderly T2DM patients (aged 65-90 years) with mild hyperglycaemia on
      diet/exercise therapy alone [glycosylated haemoglobin (HbA1c) 6.5-9.0%] or plus
      oral antidiabetic monotherapy (HbA1c 6.5-8.0%). Patients were randomized to once
      daily alogliptin 25 mg or glipizide 5 mg titrated to 10 mg, if needed.
      Hypoglycaemic episodes were systematically captured under predefined criteria.
      RESULTS: In the primary analysis, HbA1c mean changes from a baseline of 7.5% were
      -0.14% with alogliptin (n = 222) and -0.09% with glipizide (n = 219) at the end
      of the study, demonstrating non-inferiority of alogliptin to glipizide [least
      squares (LS) mean difference = -0.05%; one-sided 97.5% confidence interval (CI): 
      infinity, 0.13%]. More clinically relevant HbA1c reductions occurred among
      patients who completed the study: -0.42 and -0.33% with alogliptin and glipizide,
      with non-inferiority again confirmed (LS mean difference = -0.09%; one-sided
      97.5% CI: -infinity, 0.07%). Overall, alogliptin was safe and well tolerated,
      with notably fewer hypoglycaemic episodes than glipizide [5.4% (31 episodes) vs.
      26.0% (232 episodes), respectively]; three patients experienced severe
      hypoglycaemia, all with glipizide. Alogliptin also resulted in favourable weight
      changes versus glipizide (-0.62 vs. 0.60 kg at week 52; p < 0.001). CONCLUSIONS:
      Alogliptin monotherapy maintained glycaemic control comparable to that of
      glipizide in elderly patients with T2DM over 1 year of treatment, with
      substantially lower risk of hypoglycaemia and without weight gain.

PMID- 23531119
TI  - Low-temperature NMR studies on the geometry of base pairs involving 5-substituted
      uracil derivatives.
AB  - Uridine (U) imino proton chemical shifts, measured in the slow hydrogen-bond
      exchange regime at low temperatures in a freonic solution, show that electron
      withdrawing 5-bromo and 5-fluoro substituents on the uracil base strengthen NHN
      hydrogen bonds in (X)U.A base pairs formed by the free nucleosides. Whereas the
      halogens do not alter the preferential formation of Watson-Crick geometries, self
      associates of the halouracils point to a more favorable engagement of the 2
      carbonyl as proton acceptor in the cyclic hydrogen bonds, suggesting increased
      formation of reverse geometries and wobble base pairs with guanine when compared
      to the thymine base. Employing (15)N-labeled 5-bromouridine, no noticeable
      population of minor enol tautomers is found in the freonic mixture at 113 K.

PMID- 23531121
TI  - Targeting motility properties of bacteria in the development of probiotic
      cultures against Campylobacter jejuni in broiler chickens.
AB  - Campylobacter is the leading cause of gastroenteritis worldwide. Campylobacter is
      commonly present in the intestinal tract of poultry, and one strategy to reduce
      enteric colonization is the use of probiotic cultures. This strategy has
      successfully reduced enteric colonization of Salmonella, but has had limited
      success against Campylobacter. In an effort to improve the efficacy of probiotic
      cultures, we developed a novel in vitro screening technique for selecting
      bacterial isolates with enhanced motility. It is proposed that motility-selected
      bacteria have the marked ability to reach the same gastrointestinal niche in
      poultry and competitively reduce C. jejuni. Bacterial isolates were collected
      from ceca of healthy chickens, and motile isolates were identified and tested for
      anti-Campylobacter activity. Isolates with these properties were selected for
      increased motility by passing each isolate 10 times and at each passage selecting
      bacteria that migrated the farthest during each passage. Three bacterial isolates
      with the greatest motility (all Bacillus subtilis) were used alone or in
      combination in two chicken trials. At day of hatch, chicks were administered
      these isolates alone or in combination (n=10/treatment, two trials), and chicks
      were orally challenged with a mixture of four different wild-type strains of C.
      jejuni (~10(5) CFU/mL) on day 7. Isolate 1 reduced C. jejuni colonization in both
      of the trials (p<0.05). A follow-up study was conducted to compare isolate 1
      subjected to enhanced motility selection with its nonselected form. A reduction
      (p<0.05) in Campylobacter colonization was observed in all three trials in the
      chickens dosed using isolate with enhanced motility compared to the control and
      unselected isolate. These findings support the theory that the motility
      enhancement of potential probiotic bacteria may provide a strategy for reduction
      of C. jejuni in preharvest chickens.

PMID- 23531122
TI  - Molecular serogrouping of Shiga toxin-producing Escherichia coli using suspension
      array.
AB  - A suspension array assay was developed for molecular serotyping of the seven most
      prevalent Shiga toxin-producing Escherichia coli (STEC) serogroups (O26, O45,
      O103, O111, O121, O145, and O157). Fluorescence values of 59 STEC were 30 to >270
      times greater than the signals of negative controls, demonstrating the method's
      effectiveness for the molecular serotyping of STEC.

PMID- 23531123
TI  - Comparative analysis of the exoproteomes of Listeria monocytogenes strains grown
      at low temperatures.
AB  - This article presents the major differences in the exoproteomes of Listeria
      monocytogenes strains grown at 11 degrees C and 20 degrees C, and their
      comparison to 37 degrees C, the optimal temperature of growth of this foodborne
      pathogenic bacteria. A set of four strains previously characterized and
      representing the genetic diversity of the species was used. Two were virulent, of
      which one was persistent, and two were low virulent strains. The proteins
      secreted by the strains grown in minimal medium were separated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and identified by liquid
      chromatography tandem mass spectrometry. The heterogeneity among the four strains
      concerning the 15 major proteins detected was noticed. No clear association of
      exoproteome with virulence or genotype was found. Cluster analysis of the protein
      patterns of the strains suggests an increasing differentiation of strain response
      with low temperatures, highlighting the importance of the study of the
      exoproteomes. The main finding was the lack of some proteins in the exoproteome
      of the persistent strain, namely, flagellin (FlaA) and of OppA/oligopeptide ABC
      transporter, when compared to the other strains. In fact, these two proteins
      differ in abundance between strains grown at low temperature. Moreover, FlaA was
      the only glycoprotein identified in the exoproteomes. An attempt is made here to
      assess the relevance of the major exoproteins differentially detected. The
      investigation of the exoproteomes of other persistent and sporadic strains will
      allow identification of proteins involved in adaptation of particular L.
      monocytogenes strains to low temperatures in use throughout the food chain.

PMID- 23531124
TI  - Salmonella enterica isolated from pigeon (Columba livia) in Egypt.
AB  - Understanding the association between human salmonellosis cases and animal
      sources is an important epidemiological factor needed to successfully control the
      spread of the infection within communities. To determine the extent to which
      pigeons might harbor this pathogen and pose a risk to the human population in
      Egypt, we screened pigeons in Cairo for the presence of Salmonella relevant to
      public health and antimicrobial susceptibility testing. The isolated serotypes
      recovered from pigeon fecal samples were the following: Salmonella serotype
      Typhimurium, Braenderup, and Lomita. All strains were multiresistant. Our success
      in the isolation of Salmonella ser. Typhimurium, Braenderup, and Lomita has
      important implications because they are a significant cause of food poisoning and
      enteric fever in humans.

PMID- 23531125
TI  - A 1,681-locus consensus genetic map of cultivated cucumber including 67 NB-LRR
      resistance gene homolog and ten gene loci.
AB  - BACKGROUND: Cucumber is an important vegetable crop that is susceptible to many
      pathogens, but no disease resistance (R) genes have been cloned. The availability
      of whole genome sequences provides an excellent opportunity for systematic
      identification and characterization of the nucleotide binding and leucine-rich
      repeat (NB-LRR) type R gene homolog (RGH) sequences in the genome. Cucumber has a
      very narrow genetic base making it difficult to construct high-density genetic
      maps. Development of a consensus map by synthesizing information from multiple
      segregating populations is a method of choice to increase marker density. As
      such, the objectives of the present study were to identify and characterize NB
      LRR type RGHs, and to develop a high-density, integrated cucumber genetic
      physical map anchored with RGH loci. RESULTS: From the Gy14 draft genome, 70 NB
      containing RGHs were identified and characterized. Most RGHs were in clusters
      with uneven distribution across seven chromosomes. In silico analysis indicated
      that all 70 RGHs had EST support for gene expression. Phylogenetic analysis
      classified 58 RGHs into two clades: CNL and TNL. Comparative analysis revealed
      high-degree sequence homology and synteny in chromosomal locations of these RGH
      members between the cucumber and melon genomes. Fifty-four molecular markers were
      developed to delimit 67 of the 70 RGHs, which were integrated into a genetic map
      through linkage analysis. A 1,681-locus cucumber consensus map including 10 gene
      loci and spanning 730.0 cM in seven linkage groups was developed by integrating
      three component maps with a bin-mapping strategy. Physically, 308 scaffolds with
      193.2 Mbp total DNA sequences were anchored onto this consensus map that covered
      52.6% of the 367 Mbp cucumber genome. CONCLUSIONS: Cucumber contains relatively
      few NB-LRR RGHs that are clustered and unevenly distributed in the genome. All
      RGHs seem to be transcribed and shared significant sequence homology and synteny
      with the melon genome suggesting conservation of these RGHs in the Cucumis
      lineage. The 1,681-locus consensus genetic-physical map developed and the RGHs
      identified and characterized herein are valuable genomics resources that may have
      many applications such as quantitative trait loci identification, map-based gene
      cloning, association mapping, marker-assisted selection, as well as assembly of a
      more complete cucumber genome.

PMID- 23531126
TI  - Worldwide population genetic structure of the oriental fruit moth (Grapholita
      molesta), a globally invasive pest.
AB  - BACKGROUND: Invasive pest species have large impacts on agricultural crop yields,
      and understanding their population dynamics is important for ensuring food
      security. The oriental fruit moth Grapholita molesta is a cosmopolitan pest of
      stone and pome fruit species including peach and apple, and historical records
      indicate that it has invaded North and South America, Europe, Australia and
      Africa from its putative native range in Asia over the past century. RESULTS: We
      used 13 microsatellite loci, including nine newly developed markers, to
      characterize global population structure of G. molesta. Approximately 15
      individuals from each of 26 globally distributed populations were genotyped. A
      weak but significant global pattern of isolation-by-distance was found, and G.
      molesta populations were geographically structured on a continental scale.
      Evidence does not support that G. molesta was introduced to North America from
      Japan as previously proposed. However, G. molesta was probably introduced from
      North America to The Azores, South Africa, and Brazil, and from East Asia to
      Australia. Shared ancestry was inferred between populations from Western Europe
      and from Brazil, although it remains unresolved whether an introduction occurred
      from Europe to Brazil, or vice versa. Both genetic diversity and levels of
      inbreeding were surprisingly high across the range of G. molesta and were not
      higher or lower overall in introduced areas compared to native areas. There is
      little evidence for multiple introductions to each continent (except in the case
      of South America), or for admixture between populations from different origins.
      CONCLUSIONS: Cross-continental introductions of G. molesta appear to be
      infrequent, which is surprising given its rapid worldwide expansion over the past
      century. We suggest that area-wide spread via transport of fruits and other plant
      materials is a major mechanism of ongoing invasion, and management efforts should
      therefore target local and regional farming communities and distribution
      networks.

PMID- 23531127
TI  - Acceptance of routine or case-based inquiry for intimate partner violence: a
      mixed method study.
AB  - BACKGROUND: The prevalence and detrimental health effects of intimate partner
      violence have resulted in international discussions and recommendations that
      health care professionals should screen women for intimate partner violence
      during general and antenatal health care visits. Due to the lack of discussion on
      routine or case-based inquiry for intimate partner violence during antenatal care
      in Germany, this study seeks to explore its acceptability among pregnant German
      women. METHODS: A mixed methods approach was used, utilizing a self-administered
      survey on the acceptability of routine or case-based inquiry for intimate partner
      violence in a university hospital's maternity ward in Munich and in-depth
      interviews with seven women who experienced violence during pregnancy. RESULTS:
      Of the 401 women who participated in the survey, 92 percent were in favor of
      routine or case-based inquiry for intimate partner violence during antenatal
      care. Acceptance of routine or case-based inquiry for intimate partner violence
      during antenatal care was significantly associated with women's experiences of
      child sexual abuse, being young, less educated, single or divorced and smoking
      during pregnancy. Open-ended survey questions and in-depth interviews stressed
      adequate training for screening, sufficient time and provision of referral
      information as important conditions for routine or case-based inquiry for
      intimate partner violence. CONCLUSIONS: Women in this study showed an
      overwhelming support for routine or case-based screening for intimate partner
      violence in antenatal care in Germany. Until adequate training is in place to
      allow providers to inquire for intimate partner violence in a professional
      manner, this study recommends that health care providers are made aware of the
      prevalence and health consequences of violence during pregnancy.

PMID- 23531128
TI  - State-scale perspective on water use and production associated with oil and gas
      operations, Oklahoma, U.S.
AB  - A common goal of water and energy management is to maximize the supply of one
      while minimizing the use of the other, so it is important to understand the
      relationship between water use and energy production. A larger proportion of
      horizontal wells and an increasing number of hydraulically fractured well bores
      are being completed in the United States, and consequently increasing water
      demand by oil and gas operations. Management, planning, and regulatory decisions
      for water, oil, and gas are largely made at the state-level; therefore, it is
      necessary to aggregate water use and energy production data at the state-scale.
      The purpose of this paper is to quantify annual volumes of water used for
      completion of oil and gas wells, coproduced during oil and gas production,
      injected via underground injection program wells, and used in water flooding
      operations. Data from well completion reports, and tax commission records were
      synthesized to arrive at these estimates for Oklahoma. Hydraulic fracturing
      required a median fluid volume of 11,350 m(3) per horizontal well in Oklahoma.
      Median fluid volume (~15,774 m(3)) and volume per perforated interval (15.73 m(3)
      m(-1)) were highest for Woodford Shale horizontal wells. State-scale annual water
      use for oil and gas well completions was estimated to be up to 16.3 Mm(3) in 2011
      or less than 1% of statewide freshwater use. Statewide annual produced water
      volumes ranged from 128.5 to 146.6 Mm(3), with gas wells yielding an estimated
      72.4% of the total coproduced water. Volumes of water injected into underground
      injection control program wells ranged from 206.8 to 305.4 Mm(3), which indicates
      that water flooding operations may use up to 167.0 Mm(3) per year. State-scale
      water use estimates for Oklahoma could be improved by requiring oil and gas
      operators to supplement well completion reports with water use and water
      production data. Reporting of oil and gas production data by well using a unique
      identifier (i.e., API number) would also allow for refinement of produced water
      quantity information. Reporting of wastewater disposal and water flooding volumes
      could be used to further develop state-scale water accounting and best management
      practices.

PMID- 23531129
TI  - Comparative ethnoentomology of edible stinkbugs in southern Africa and
      sustainable management considerations.
AB  - Insects, such as stinkbugs, are able to produce noxious defence chemicals to ward
      off predators, nevertheless, some ethnic groups have recipes to render them
      delicious. We provide an example of edible stinkbugs (Encosternum delegorguei)
      used by two locally separate ethnic groups in South Africa, the Vhavenda and
      Mapulana, with a third group, the Bolobedu using them for commercial purposes.
      Structured interview schedules and observations with 106 harvesters were
      conducted to determine differences in use, nomenclature and oral history, methods
      of collection and preparation as well as perceptions pertaining to availability.
      The stinkbugs' foul defence chemical and flight response necessitates nocturnal
      harvesting when the insect is immobilised by cold. The defence chemical stains
      the skin and affects vision yet protective gear is not worn. Damage to host trees
      was recorded when harvesters poached from plantations or private land, whereas,
      in communal-lands, sustainable methods were preferred. The legitimisation of
      stinkbug harvesting and introduction of a collection funnel could reduce
      conflicts with managers of plantations and private land. Two methods to remove
      the defence chemical for increased palatability were used. Preparation methods
      differed in whether or not water was used and also whether the head was left
      intact or removed. Stinkbugs have numerous medicinal uses, in particular as a
      hangover cure. Awareness and optimal use of beneficial insects, such as
      stinkbugs, in rural areas could lead to a reconsideration of current
      environmental management strategies, where harvesters act as habitat stewards and
      clearing, grazing or burning indigenous vegetation is kept to a minimum.

PMID- 23531120
TI  - High-sensitivity analytical approaches for the structural characterization of
      glycoproteins.

PMID- 23531130
TI  - The utility of recombinant factor VIIa as a last resort in trauma.
AB  - INTRODUCTION: The use of recombinant factor VII (rFVIIa) as a last resort for the
      management of coagulopathy when there is severe metabolic acidosis during large
      bleedings in trauma might be deemed inappropriate. The objective of this study
      was to identify critical degrees of acidosis and associated factors at which
      rFVIIa might be considered of no utility. METHODS: All massively transfused (>= 8
      units of red blood cells within 12 hours) trauma patients from Jan 2000 to Nov
      2006. Demographic, baseline physiologic and rFVIIa dosage data were collected.
      Rate of red blood cell transfusion in the first 6 hours of hospitalization
      (RBC/hr) was calculated and used as a surrogate for bleeding. Last resort use of
      rFVIIa was defined by a pH<= 7.02 based on ROC analysis for survival. In-hospital
      mortality was analyzed in last resort and non-last resort groups. Univariate
      analysis was performed to assess for differences between groups and identify
      factors associates with no utility of rFVIIa. RESULTS: 71 patients who received
      rFVIIa were analyzed. The pH> 7.02 had 100% sensitivity for the identification of
      potential survivors. All 11 coagulopathic, severely acidotic (pH <= 7.02)
      patients with high rates of bleeding (4RBC/hr) died despite administration of
      rFVIIa. The financial cost of administering rFVIIa as a last resort to these 11
      severely acidotic and coagulophatic cases was $75,162 (CA). CONCLUSIONS: Our
      study found no utility of rFVIIa in treating severely acidotic, coagulopathic
      trauma patients with high rates of bleeding; and thus restrictions should be set
      on its usage in these circumstances.

PMID- 23531132
TI  - Foreword.

PMID- 23531133
TI  - Cytotoxic natural products from thai plants: a recent study.
AB  - Natural products will continue to be the most prolific source of bioactive
      compounds. Natural products exhibiting antitumor activity continue to be the
      subject of extensive research aimed at the development of drugs for the treatment
      of different human tumors. It is generally accepted that natural products offer a
      diversity and complexity of structure unmatched by even the most active
      imaginations of synthetic organic chemists. This paper reviews the research of
      selected Thai plants for the discovery of therapeutic agents. Attention will be
      focused on our recent research on Thai plants that possess cytotoxic properties.
      Synthetic modification and reaction of some of these compounds aimed at enhancing
      their potency will also be presented.

PMID- 23531131
TI  - Peptidoglycan transformations during Bacillus subtilis sporulation.
AB  - While vegetative Bacillus subtilis cells and mature spores are both surrounded by
      a thick layer of peptidoglycan (PG, a polymer of glycan strands cross-linked by
      peptide bridges), it has remained unclear whether PG surrounds prespores during
      engulfment. To clarify this issue, we generated a slender DeltaponA mutant that
      enabled high-resolution electron cryotomographic imaging. Three-dimensional
      reconstructions of whole cells in near-native states revealed a thin PG-like
      layer extending from the lateral cell wall around the prespore throughout
      engulfment. Cryotomography of purified sacculi and fluorescent labelling of PG in
      live cells confirmed that PG surrounds the prespore. The presence of PG
      throughout engulfment suggests new roles for PG in sporulation, including a new
      model for how PG synthesis might drive engulfment, and obviates the need to
      synthesize a PG layer de novo during cortex formation. In addition, it reveals
      that B. subtilis can synthesize thin, Gram-negative-like PG layers as well as its
      thick, archetypal Gram-positive cell wall. The continuous transformations from
      thick to thin and back to thick during sporulation suggest that both forms of PG
      have the same basic architecture (circumferential). Endopeptidase activity may be
      the main switch that governs whether a thin or a thick PG layer is assembled.

PMID- 23531134
TI  - Bioactive saponins in vietnamese ginseng, panax vietnamensis.
AB  - Vietnamese ginseng, Panax vietnamensis was recently found in central Vietnam, and
      regarded as a new botanical species. It was used in traditional folk medicine in
      hill tribes for the purpose of anti-fatigue and life saving. From the rhizome and
      root of this plant, 37 saponins including 14 new compounds were isolated. Some of
      them were common to other Panax spp., but the general yields in this species were
      very high. Among them, an ocotillol-type saponin majonoside-R2 (MR2) was
      remarkable in its yield (5.3%). Structural features of new saponins were briefly
      introduced. The biological effects of these saponins were studied in two ways,
      anti-stress effect and anti-tumor promoting effect; both activities were based
      upon the traditional usage of this crude drug. In psychologically stressed mice,
      the saponin fraction of Vietnamese ginseng significantly reduced stress-related
      disorders (reducing sleeping time, formation of gastric lesions) and MR2 was
      responsible for this effect. A possible mechanism for this effect was proposed.
      MR2 exhibited a significant inhibitory effect on Epstein-Barr virus early antigen
      (EBV-EA) induced by the tumor promoter phorbol acetate. MR2 also showed potent
      anti-tumor-promoting activity on mouse skin and hepatic tumors.

PMID- 23531135
TI  - Phytochemical investigation of some traditional chinese medicines and endophyte
      cultures.
AB  - For many social and environmental reasons, over the last few decades, there has
      been an increase in chronic and life-threatening diseases including mycoses,
      hyperuricemia-related disorders and some mental illnesses such as depression,
      anxiety and Parkinson's disease. In order to fight these diseases, compounds
      acting on various biological targets, including enzymes such as xanthine oxidase
      or monoamine oxidase, have to be screened. The enzyme xanthine oxidase catalyses
      the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a
      crucial role in hyperuricemiarelated disorders such as gout and renal stones. One
      of the therapeutic approaches to treat these diseases is the use of xanthine
      oxidase inhibitors that block the production of uric acid. Monoamine oxidases
      (E.C.1.4.3.4) A and B catalyse the oxidative deamination of monoamines in the
      central nervous system and peripheral tissues. Inhibitors of MAO A are clinically
      useful to treat anxiety and depression since they are expected to increase both
      noradrenalin and serotonin levels in the brain. On the other hand, inhibition of
      MAO B appears to be an effective approach for the prevention and adjunct
      treatment of Parkinson's disease. In traditional Chinese medical practice, many
      medicinal herbs have been used to treat chronic diseases such as fungal
      infections, hyperuricemia-based disorders and mental illnesses. This usage is
      indicative for the presumable presence of antifungal phytochemicals and
      inhibitors of xanthine and monoamine oxidases. Plants do not represent the only
      source for interesting natural products; some endophytes ('special'
      microorganisms living inside the healthy host plant) are also known to produce
      secondary metabolites of promising pharmaceutical and/or agricultural potential.
      The above observations prompted us to search for natural antifungal compounds and
      inhibitors of xanthine and monoamine oxidases in different Chinese plants and
      endophyte cultures. The active constituents isolated were mainly mono-, sesqui-,
      di-, and triterpenes, sterols, coumarins, flavonoids, phenylethanoids,
      stilbenoids, alkaloids and alcohols.

PMID- 23531136
TI  - Immunomodulating components from chinese medicines.
AB  - Modern scientific studies have shown that several components from Chinese herbal
      medicines are immunologically active. Astragalus mongholicus polysaccharide APS,
      a polymer of glucose and arabinose, increases specific antibody formation as well
      as synthesis of RNA, DNA and protein in mouse spleen. The polysaccharide PES
      isolated from Acanthopanax senticosus used as a tonic and sedative agent also
      induces interferon production. An oligosaccharide AbPS isolated from Achyranthes
      bidentata with a mw of only 1360 Da significantly enhances the humoral immune
      response and antagonizes the immunosuppressive effects of cyclosporin A. AbPS
      increases the production of TNF and the activity of NK cells. In tumor patients
      treated by chemotherapy or radiotherapy, AbPS maintained their peripheral white
      blood cell count and improved the quality of life. PSP, the protein bound
      polysaccharide extracted from Coriolus versicolor , has been developed as an
      anticancer drug in China. It promoted T cell proliferation, increased NK and LAK
      cell activities as well as anticancer cytokines IL-2, IL-6, IFN-? and TNF-a
      production so as to induce tumor cell apoptosis. Celastrol, a triterpene compound
      isolated from Tripterygium wilfordii was proven to be an equally-strong
      immunosuppressor and inhibited free radical damage in experimental arthritis.
      Ginkgo biloba extract improves cognitive functions. Ginkgolide A and B inhibited
      IL-1, TNF-a and nitric oxide production in rat microglia and prevented the
      chronic inflammatory process in neurodegenerative diseases.

PMID- 23531137
TI  - The Importance Of LC-MS And LC-NMR In The Discovery Of New Lead Compounds From
      Plants.
AB  - Rapid detection of biologically active natural products plays a key role in the
      phytochemical investigation of crude plant extracts. In order to perform an
      efficient screening of the extracts, both biological assays and HPLC analysis
      with various detection methods are used. Techniques such as HPLC coupled to UV
      photodiode array detection (LC/DAD-UV) and to mass spectrometry (LC/MS or
      LC/MS/MS) provide numerous on-line structural data on the metabolites prior to
      isolation. The recent introduction of HPLC coupled to nuclear magnetic resonance
      (LC/NMR) represents a powerful complement to LC/UV/MS screening. Various plant
      species belonging to the Gentianaceae and Leguminosae have been analysed by
      LC/UV, LC/MS, LC/MS/MS and LC/NMR. These hyphenated techniques allow a rapid
      structural determination of known plant constituents with only a minute amount of
      plant material. Simple bioautographic assays such as those used for screening
      antifungal constituents can also be performed on-line directly by collecting HPLC
      peaks and measuring the activity against the fungi of interest. These bioassays
      permit a rapid localisation of the bioactive natural products. With such a
      combined approach, the time consuming isolation of common natural products is
      avoided and an efficient targeted isolation of compounds presenting interesting
      spectroscopical or biological features is performed. Several representative
      applications of the use of LC/MS and LC/NMR for the dereplication and
      identification of antifungal constituents are presented in the present paper.

PMID- 23531138
TI  - Chemical investigation of mammea siamensis.
AB  - A new 4-alkylcoumarin, mammea B/AC cyclo D ( 1 ), together with a 4
      phenylcoumarin, mammea A/AC cyclo D ( 2 ), were isolated from the hexane extract
      of the dried flower of Mammea siamensis . Their structures were determined on the
      basis of spectroscopic evidence.

PMID- 23531139
TI  - NMR study of seven coumarins from mammea siamensis.
AB  - Seven known mammea coumarins, mammea A/AA cyclo D ( 1 ), mammea A/AD cyclo D ( 2
      ), mammea A/AB cyclo D ( 3 ), mammea A/AC cyclo F ( 4 ), mam-mea A/AB cyclo F ( 5
      ), mammea A/AA cyclo F ( 6 ), mammea B/AC cyclo F ( 7 ), were isolated for the
      first time from the hexane extract of Mammea siamensis . A detailed analysis of
      both 1D and 2D NMR spectral data of these compounds was made.

PMID- 23531140
TI  - Reinvestigation of derris reticulata.
AB  - The novel compound 1'''-hydroxy-2''',3'''-epoxylupinifolin ( 1 ), together with
      three known prenylated flavanones were identified from the stem of Derris
      reticulata during our reinvestigation of the plant. The structures were
      determined by spectroscopic methods including detailed study of NMR spectral data
      (DEPT, 2D-COSY, HMQC and HMBC) as well as by chemical derivatizations.

PMID- 23531141
TI  - Endoloop retraction technique in single-port laparoscopic cholecystectomy:
      experience in 27 patients.
AB  - BACKGROUND: Single-port laparoscopic cholecystectomy (SPLC) has been one of the
      hottest topics in minimally invasive surgery. Various techniques have been
      described, but the search for better techniques and equipment still continues.
      The aim of this study is to share a new retraction technique and the results in
      27 patients. PATIENTS AND METHODS: Between May 2010 and May 2011, 27 patients
      underwent SPLC with the presented technique. The data related to the operative
      and postoperative measures were collected prospectively. Operation time, pain
      score (visual analog scale) in the first 24 hours after the operation, and length
      of hospital stay were recorded by an independent nurse. RESULTS: Twenty-seven
      SPLCs were performed. Indications were symptomatic gallstone disease or
      gallbladder polyps without active inflammation. Mean operation time was 45.7
      minutes (range, 30-80 minutes). In none of the patients was introduction of an
      additional port or conversion to conventional laparoscopic cholecystectomy
      needed. CONCLUSIONS: The endoloop technique can be used to overcome retraction
      problem while preventing spillage of bile and reducing crowding of instruments
      with a practically invisible scar in selected patients.

PMID- 23531142
TI  - Robotic repair of post-cystectomy ureteroileal anastomotic strictures: techniques
      for success.
AB  - INTRODUCTION: Post-cystectomy ureteroileal anastomotic strictures that fail
      percutaneous or endourologic management require operative repair. These cases can
      be challenging, and few reports of robotic repairs exist in the available
      literature. Here we describe our stepwise approach to robotic surgical repair of
      ureteroileal strictures. TECHNIQUE: The da Vinci((r)) Si Surgical System
      (Intuitive Surgical, Sunnyvale, CA) was used in all cases. The port configuration
      is similar to robotic cystectomy, although the ports are placed in a more
      cephalad location on the abdominal wall. The same port configuration was used for
      both right- and left-sided procedures. Principal surgical techniques used include
      dissection of the colonic mesentery, careful peeling of the ureter off of the
      common iliac vessels, and mobilization of the ureter on either side of the
      sigmoid colon. RESULTS: Four patients with a mean age of 72 years underwent this
      procedure at our institution, including 2 with left-sided strictures and 2 with
      right-sided strictures. Three of the 4 patients had undergone prior abdominal
      surgery in addition to their cystectomy. All patients failed initial percutaneous
      and/or endourologic attempts to resolve their stricture. The ureteroileal
      strictures were successfully repaired robotically in all cases. With mean follow
      up of 16 months no major complications were encountered, and all patients remain
      free of stricture recurrence to date. CONCLUSIONS: Robotic ureteroileal
      anastomotic stricture repair is feasible for both right- and left-sided cases. A
      similar operative approach can be used regardless of stricture side.

PMID- 23531143
TI  - The effect of ethanol and acetaldehyde on brain ependymal and respiratory ciliary
      beat frequency.
AB  - BACKGROUND: Ethanol has been shown to stimulate the beat frequency of respiratory
      cilia at concentrations encountered during social drinking, while one of its
      metabolites, acetaldehyde, has been shown to cause a marked decrease in ciliary
      beat frequency. The aim of this study was to determine whether short-term
      exposure to ethanol stimulated ependymal cilia and whether exposure to
      acetaldehyde had a toxic effect on ependymal and respiratory cilia. METHODS:
      Using ex vivo rat ependymal brain slice and human nasal brush biopsy models, we
      investigated the effect of exposure of cilia to various concentrations of ethanol
      and acetaldehyde at either 37 degrees C or 24 degrees C. Ciliary beat frequency
      was measured using digital high-speed video analysis. RESULTS: Exposure of
      ependymal and respiratory cilia to control, 0.1%, 0.5% and 1% ethanol solutions
      resulted in a maximal increase of 15% in the ciliary beat frequency from baseline
      values, compared with the control of 6%. A one-way analysis of variance comparing
      the mean slopes for the three concentrations of ethanol and control showed no
      significant differences between the groups (P >0.05). Exposure of ependymal and
      respiratory cilia to 100 and 250 MUM acetaldehyde solutions resulted in a maximal
      increase of 15% in the ciliary beat frequency from baseline, compared with the
      control of 12%. A one-way analysis of variance performed to compare the mean
      slopes in these groups showed no significant differences (P >0.05). CONCLUSIONS:
      Short-term exposure of brain ependymal and respiratory cilia to the
      concentrations of ethanol likely to be encountered during episodes of heavy
      drinking and to acetaldehyde at concentrations well above those encountered by
      man did not have a significant effect on ciliary beat frequency.

PMID- 23531144
TI  - Effects of hospitalist-directed interdisciplinary medicine floor service on
      hospital outcomes for seniors with acute medical illness.
AB  - AIM: To examine whether a hospitalist-directed interdisciplinary (ITD) team in an
      internal medicine residency program enhances the hospital and clinical outcomes
      for seniors with acute medical illness. METHODS: Seniors admitted to a USA
      teaching hospital medical floor-teaching services were allocated to the ITD (n =
      379) and usual care teams (n = 383). Compared with the usual care team, the ITD
      team physicians carried out daily "geriatric" assessment and management, and led
      ITD team meetings. RESULTS: The mean probability of functional decline on
      hospital discharge in the ITD team (25%; 95% CI 19-30%) was significantly lower
      than that in the usual care team (36%; 95% CI 30-43%; OR 0.35; 95% CI 0.10-0.92;
      P < 0.001). The mean probability of delirium in the ITD team (26%; 95% CI 20-32%)
      was significantly lower than that in the usual care team (34%; 95% CI 28-41%; OR
      0.48; 95% CI 0.16-0.97; P = 0.03). The mean probability of transition to an
      institution in the ITD team (18%; 95% CI 13-23%) was significantly lower than
      that in the usual care team (26%; 95% CI 19-32%; OR 0.41; 95% CI 0.14-0.95; P =
      0.01). CONCLUSIONS: Hospitalist-directed ITD team care is associated with
      reductions of functional decline, delirium and transition to an institution for
      seniors with acute medical illness.

PMID- 23531145
TI  - Prevalence of gastroduodenal ulcers/erosions in patients taking low-dose aspirin
      with either 15 mg/day of lansoprazole or 40 mg/day of famotidine: the OITA-GF
      study 2.
AB  - BACKGROUND: The preventive effects of histamine 2 receptor antagonists vs. proton
      pump inhibitors on low-dose aspirin (LDA)-related gastroduodenal mucosal injury
      have not been fully investigated. We conducted a cross-sectional study to compare
      the prevalence of gastroduodenal ulcers or erosions in patients taking LDA with
      either 40 mg/day of famotidine or 15 mg/day of lansoprazole for at least three
      months. METHODS: Of 84 eligible patients, two taking 40 mg/day of famotidine and
      four taking 15 mg/day of lansoprazole refused to undergo upper gastrointestinal
      endoscopy. Ultimately, we performed upper gastrointestinal endoscopy in 78
      patients taking either 40 mg/day of famotidine (group F, n = 31) or 15 mg/day of
      lansoprazole (group L, n = 47). The prevalence of gastroduodenal ulcers or
      erosions and the magnitude of gastric mucosal injury evaluated using modified
      Lanza scores were compared between the two groups. RESULTS: No patients in either
      group had gastroduodenal ulcers. Gastroduodenal erosions were more prevalent in
      group F than in group L (48.4% vs. 17.0%, p = 0.005). The modified Lanza scores
      (mean +/- SD) were significantly higher in group F than in group L (0.9 +/- 1.3
      vs. 0.3 +/- 0.7, p = 0.007). A multivariate logistic regression analysis showed
      that the use of lansoprazole was negatively associated with gastroduodenal
      erosions. CONCLUSIONS: This study suggests that 15 mg/day of lansoprazole may be
      more effective in preventing the development of LDA-related gastroduodenal
      erosions than 40 mg/day of famotidine. The preventive effects of these two
      regimens on the development of LDA-related gastroduodenal ulcers require further
      investigation.

PMID- 23531146
TI  - Combination repair of a complex central facial defect using multiple flaps and
      grafts.

PMID- 23531147
TI  - C-reactive protein/oxidised low-density lipoprotein/beta2-glycoprotein I complex
      promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein
      kinase signal pathway.
AB  - BACKGROUND: The aim of this study was to investigate the effect of C-reactive
      protein/oxidised low-density lipoprotein/beta2-glycoprotein I
      (CRP/oxLDL/beta2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice.
      METHODS: BALB/c mice were fed high-fat and normal diet. Eight weeks later, the
      mice fed with high-fat diet were injected with streptozotocin (STZ) to induce
      diabetes. The diabetic mice were respectively injected twice monthly with 20 MUg
      oxLDL, 20 MUg beta2GPI, 40 MUg oxLDL/beta2GPI complex, 44 MUg CRP/oxLDL/beta2GPI
      complex, and PBS. Aortas were stained with Sudan IV to investigate lipid plaque
      formation. The infiltration condition of smooth muscle cells (SMCs), macrophages,
      and T cells in the aortas were determined by immunohistochemistry (IH). The mRNA
      expressions of receptors associated with lipid metabolism were quantified by real
      time PCR. The phosphorylation of p38 mitogen-activated protein kinase (p38MAPK)
      and MKK3/6 in aorta tissues were assessed by Western blot. The expression of
      inflammation cytokines was evaluated by protein chip. RESULTS: The lipid plaques
      were more extensive, the lumen area was obviously narrower, the ratio of intima
      and media thickness were increased, and the normal internal elastic lamia
      structure and endothelial cell disappeared (P < 0.05) in the oxLDL and
      CRP/oxLDL/beta2GPI groups (P < 0.05). CRP/oxLDL/beta2GPI complex dramatically
      promoted infiltration of SMCs, macrophages, and T cells, improved the mRNA
      expression of ABCA1 and ABCG1, but reduced the mRNA expression of SR-BI and CD36
      and increased the phosphorylation of p38MAPK and MKK3/6 (all P < 0.05). The
      highest expression levels of IL-1, IL-9, PF-4, bFGF, and IGF-II were detected in
      the CRP/oxLDL/beta2GPI group (P < 0.05). CONCLUSIONS: CRP/oxLDL/beta2GPI complex
      aggravated AS in diabetic BALB/c mice by increasing lipid uptake, the mechanism
      of which may be mediated by the p38MAPK signal pathway.

PMID- 23531148
TI  - Survival, growth and sexual maturation in Atlantic salmon exposed to infectious
      pancreatic necrosis: a multi-variate mixture model approach.
AB  - BACKGROUND: Outbreaks of infectious pancreatic necrosis (IPN) in Atlantic salmon
      can result in reduced growth rates in a fraction of the surviving fish (runts).
      Genetic and environmental variation also affects growth rates within different
      categories of healthy animals and runts, which complicates identification of
      runts. Mixture models are commonly used to identify the underlying structures in
      such data, and the aim of this study was to develop Bayesian mixture models for
      the genetic analysis of health status (runt/healthy) of surviving fish from an
      IPN outbreak. METHODS: Five statistical models were tested on data consisting of
      10 972 fish that died and 3959 survivors with recorded growth data. The most
      complex models (4 and 5) were multivariate normal-binary mixture models including
      growth, sexual maturity and field survival traits. Growth rate and liability of
      sexual maturation were treated as two-component normal mixtures, assuming
      phenotypes originated from two potentially overlapping distributions,
      (runt/normal). Runt status was an unobserved binary trait. These models were
      compared to mixture models with fewer traits (Models 2 and 3) and a classical
      linear animal model for growth (Model 1). RESULTS: Assuming growth as a mixture
      trait improved the predictive ability of the statistical model considerably
      (Model 2 vs. 1). The final models (4 and 5) yielded the following results:
      estimated (underlying) heritabilities were moderate for growth in healthy fish
      (0.32 +/- 0.04 and 0.35 +/- 0.05), runt status (0.39 +/- 0.07 and 0.36 +/- 0.08)
      and sexual maturation (0.33 +/- 0.05), and high for field survival (0.47 +/- 0.03
      and 0.48 +/- 0.03). Growth in healthy animals, runt status and survival showed
      consistent favourable genetic associations. Sexual maturation showed an
      unfavourable non-significant genetic correlation with runt status, but favourable
      genetic correlations with other traits. The estimated fraction of healthy fish
      was 81-85%. The estimated breeding values for runt status and (normal) growth
      were consistent for the most complex models (4 and 5), but showed imperfect
      correlations with estimated breeding values from the simpler models. CONCLUSIONS:
      Modelling growth in IPN survivors as a mixture trait improved the predictive
      ability of the model compared with a classical linear model. The results
      indicated considerable genetic variation in health status among survivors.
      Mixture modelling may be useful for the genetic analysis of diseases detected
      mainly through indicator traits.

PMID- 23531149
TI  - Striking reduction of amyloid plaque burden in an Alzheimer's mouse model after
      chronic administration of carmustine.
AB  - BACKGROUND: Currently available therapies for Alzheimer's disease (AD) do not
      treat the underlying cause of AD. Anecdotal observations in nursing homes from
      multiple studies strongly suggest an inverse relationship between cancer and AD.
      Therefore, we reasoned that oncology drugs may be effective against AD. METHODS:
      We screened a library of all the FDA-approved oncology drugs and identified bis
      chloroethylnitrosourea (BCNU or carmustine) as an effective amyloid beta (Abeta)
      reducing compound. To quantify Abeta levels, Chinese hamster ovary (CHO) cells
      stably expressing amyloid precursor protein 751WT (APP751WT) called 7WD10 cells
      were exposed to different concentrations of BCNU for 48 hours and the conditioned
      media were collected. To detect Abeta the conditioned media were
      immunoprecipitated with Ab9 antibody and subjected to immunoblot detection.
      Amyloid plaques were quantified in the brains of a mouse model of AD after
      chronic exposure to BCNU by thoflavin S staining. RESULTS: BCNU decreased
      normalized levels of Abeta starting from 5 MUM by 39% (P < 0.05), 10 MUM by 51%
      (P < 0.01) and 20 MUM by 63% (P < 0.01) in CHO cells compared to a control group
      treated with butyl amine, a structural derivative of BCNU. Interestingly, soluble
      amyloid precursor protein alpha (sAPPalpha) levels were increased to 167% (P <
      0.01) at 0.5 MUM, 186% (P < 0.05) at 1 MUM, 204% (P < 0.01) at 5 MUM and 152% (P
      < 0.05) at 10 MUM compared to untreated cells. We also tested the effects of 12
      structural derivatives of BCNU on Abeta levels, but none of them were as potent
      as BCNU. BCNU treatment at 5 MUM led to an accumulation of immature APP at the
      cell surface resulting in an increased ratio of surface to total APP by 184% for
      immature APP, but no change in mature APP. It is also remarkable that BCNU
      reduced Abeta generation independent of secretases which were not altered up to
      40 MUM. Interestingly, levels of transforming growth factor beta (TGFbeta) were
      increased at 5 MUM (43%, P < 0.05), 10 MUM (73%, P < 0.01) and 20 MUM (92%, P <
      0.001). Most significantly, cell culture results were confirmed in vivo after
      chronic administration of BCNU at 0.5 mg/kg which led to the reduction of Abeta40
      by 75% and amyloid plaque burden by 81%. Conversely, the levels of sAPPalpha were
      increased by 45%. CONCLUSIONS: BCNU reduces Abeta generation and plaque burden at
      non-toxic concentrations possibly through altered intracellular trafficking and
      processing of APP. Taken together these data provided unequivocal evidence that
      BCNU is a potent secretase-sparing anti-Abeta drug. See related commentary
      article here http://www.biomedcentral.com/1741-7015/11/82.

PMID- 23531150
TI  - Effect of exercise on blood flow through the aortic valve: a combined clinical
      and numerical study.
AB  - The aim of this study was to measure the cardiac output and stroke volume for a
      healthy subject by coupling an echocardiogram Doppler (echo-Doppler) method with
      a fluid-structure interaction (FSI) simulation at rest and during exercise. Blood
      flow through aortic valve was measured by Doppler flow echocardiography. Aortic
      valve geometry was calculated by echocardiographic imaging. An FSI simulation was
      performed, using an arbitrary Lagrangian-Eulerian mesh. Boundary conditions were
      defined by pressure loads on ventricular and aortic sides. Pressure loads applied
      brachial pressures with (stage 1) and without (stage 2) differences between
      brachial, central and left ventricular pressures. FSI results for cardiac output
      were 15.4% lower than Doppler results for stage 1 (r = 0.999). This difference
      increased to 22.3% for stage 2. FSI results for stroke volume were undervalued by
      15.3% when compared to Doppler results at stage 1 and 26.2% at stage 2 (r =
      0.94). The predicted mean backflow of blood was 4.6%. Our results show that
      numerical methods can be combined with clinical measurements to provide good
      estimates of patient-specific cardiac output and stroke volume at different heart
      rates.

PMID- 23531151
TI  - Direct evidence for hydrogen bonding in glycans: a combined NMR and molecular
      dynamics study.
AB  - We introduce the abundant hydroxyl groups of glycans as NMR handles and
      structural probes to expand the repertoire of tools for structure-function
      studies on glycans in solution. To this end, we present the facile detection and
      assignment of hydroxyl groups in a wide range of sample concentrations (0.5-1700
      mM) and temperatures, ranging from -5 to 25  degrees C. We then exploit this
      information to directly detect hydrogen bonds, well-known for their importance in
      molecular structural determination through NMR. Via HSQC-TOCSY, we were able to
      determine the directionality of these hydrogen bonds in sucrose. Furthermore, by
      means of molecular dynamics simulations in conjunction with NMR, we establish
      that one out of the three detected hydrogen bonds arises from intermolecular
      interactions. This finding may shed light on glycan-glycan interactions and
      glycan recognition by proteins.

PMID- 23531152
TI  - Genetic analysis of tolerance to boron toxicity in the legume Medicago
      truncatula.
AB  - BACKGROUND: Medicago truncatula Gaertn. (barrel medic) is cultivated as a pasture
      legume for its high protein content and ability to improve soils through nitrogen
      fixation. Toxic concentrations of the micronutrient Boron (B) in agricultural
      soils hamper the production of cereal and leguminous crops. In cereals, the
      genetic analysis of B tolerance has led to the development of molecular selection
      tools to introgress and maintain the B tolerance trait in breeding lines. There
      is a comparable need for selection tools in legumes that grow on these toxic
      soils, often in rotation with cereals. RESULTS: Genetic variation for B tolerance
      in Medicago truncatula was utilised to generate two F2 populations from crosses
      between tolerant and intolerant parents. Phenotyping under B stress revealed a
      close correlation between B tolerance and biomass production and a segregation
      ratio explained by a single dominant locus. M. truncatula homologues of the
      Arabidopsis major intrinsic protein (MIP) gene AtNIP5;1 and the efflux-type
      transporter gene AtBOR1, both known for B transport, were identified and nearby
      molecular markers screened across F2 lines to verify linkage with the B-tolerant
      phenotype. Most (95%) of the phenotypic variation could be explained by the SSR
      markers h2_6e22a and h2_21b19a, which flank a cluster of five predicted MIP genes
      on chromosome 4. Three CAPS markers (MtBtol-1,-2,-3) were developed to dissect
      the region further. Expression analysis of the five predicted MIPs indicated that
      only MtNIP3 was expressed when leaf tissue and roots were assessed. MtNIP3 showed
      low and equal expression in the roots of tolerant and intolerant lines but a 4
      fold higher expression level in the leaves of B-tolerant cultivars. The
      expression profile correlates closely with the B concentration measured in the
      leaves and roots of tolerant and intolerant plants. Whereas no significant
      difference in B concentration exists between roots of tolerant and intolerant
      plants, the B concentration in the leaves of tolerant plants is less than half
      that of intolerant plants, which further supports MtNIP3 as the best candidate
      for the tolerance trait-defining gene in Medicago truncatula. CONCLUSION: The
      close linkage of the MtNIP3 locus to B toxicity tolerance provides a source of
      molecular selection tools to pasture breeding programs. The economical importance
      of the locus warrants further investigation of the individual members of the MIP
      gene cluster in other pasture and in grain legumes.

PMID- 23531153
TI  - Acral vitiligo and lesions over joints treated with non-cultured epidermal cell
      suspension transplantation.
AB  - BACKGROUND: Vitiligo is a disfiguring condition that can cause considerable
      psychological distress to patients. Vitiligo lesions on acral areas and joints
      are considered difficult to treat, and they are unsuitable for surgical treatment
      because of their poor response. There are few studies on the management of those
      lesions with noncultured epidermal cell suspension transplantation. AIM: To
      evaluate the efficacy of a modified procedure using noncultured epidermal cell
      suspension transplantation in the management of vitiligo lesions over acral areas
      and joints. METHODS: We retrospectively analysed data for patients who had
      undergone non-cultured epidermal cell suspension transplantation for treatment of
      vitiligo. In total, 36 patients with 80 lesions over acral areas and joints were
      reviewed: 33 patients had generalized vitiligo, while the remaining three
      patients had focal vitiligo, and they had been followed up for 6-18 months.
      RESULTS: Of the 80 treated lesions, 51 had regained > 75% repigmentation and 23
      had regained 50-75% repigmentation. The remaining six lesions, which were all no
      the distal fingers or toes and the ankle joint, had a poor response. CONCLUSIONS:
      Non-cultured epidermal cell suspension transplantation was successful in
      producing some degree of repigmentation in our patients, and could be a useful
      therapy for vitiligo lesions.

PMID- 23531154
TI  - Progression to insulin for patients with diabetes mellitus on dual oral
      antidiabetic therapy using the US Department of Defense Database.
AB  - AIM: To compare 'progression to insulin' for three cohorts on oral antidiabetic
      medication combinations: metformin/sulphonylurea (Met/SU),
      metformin/thiazolidinedione (Met/TZD) and sulphonylurea/thiazolidinedione
      (SU/TZD). METHODS: Retrospective cohort analysis design was used. The subjects
      were US nationwide members of military and their families. A total of 5608
      patients who were on antidiabetic monotherapy for at least 1 year before adding a
      second agent to their medication regimen between October 2001 and September 2008
      participated in this study. Mean age ranged from 64 to 71 years among the
      cohorts. Cox regression compared the progression to insulin, adjusting for
      demographics, months of follow-up and co-morbidities [measured with Chronic
      Disease Score (CDS)]. RESULTS: By the end of the 2- to 6-year follow-up period,
      14.3% of the Met/TZD cohort, 23.6% of the Met/SU cohort and 28.2% of the SU/TZD
      cohort had insulin added to their regimen. Those in the Met/SU cohort had a 1.8
      times higher probability of progression to insulin than those in the Met/TZD
      cohort [odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.51-2.14), and
      those in the SU/TZD cohort had a 2.5 times higher probability of progression to
      insulin than those in the Met/TZD cohort (OR = 2.51, 95% CI = 2.04-3.08).
      CONCLUSION: When sensitizers were paired (Met/TZD), a lower percentage of
      patients progressed to insulin during the study period, as opposed to patients
      who used a combination of a secretagogue with a sensitizer (SU/TZD or Met/SU).

PMID- 23531156
TI  - LC-MS analysis with thiol derivatization to differentiate [Dhb(7)]- from
      [Mdha(7)]-microcystins: analysis of cyanobacterial blooms, Planktothrix cultures
      and European crayfish from Lake Steinsfjorden, Norway.
AB  - Kinetic studies showed that [Asp(3), Dhb(7)]MC-RR reacted with mercaptoethanol
      hundreds of times more slowly than MC-RR and a range of other [Mdha(7)]
      containing microcystin congeners. The difference in reaction rate was
      sufficiently large that derivatization of microcystin-containing samples with
      mercaptoethanol, followed by LC-MS analysis, clearly discriminated between
      microcystins containing the isobaric [Dhb(7)]- and [Mdha(7)]-groups. Application
      of this approach, using LC-MS with both-ion trap and triple-quadrupole mass
      spectrometers, to water samples and Planktothrix cultures from Lake
      Steinsfjorden, Norway, demonstrated the presence of [Asp(3), Dhb(7)]MC-RR (5),
      [Asp(3)]MC-RY (14), and [Asp(3)]MC-LY (16), as well as analogues tentatively
      identified as [Asp(3)]MC-RR (4), [Asp(3), DMAdda(5), Dhb(7)]MC-LR (6), [Asp(3),
      Dhb(7)]MC-HtyR (8), [Asp(3)]MC-HtyR (9), [Asp(3), Dhb(7)]MC-LR (10), [Asp(3)]MC
      LR (11), [Asp(3), Dhb(7)]MC-RY (15), and [Asp(3), Dhb(7)]MC-LY (17), together
      with low levels of several other analogues. This is the first use of this thiol
      based LC-MS approach to identify Dhb-containing microcystins, and allowed
      identification of LC-MS peaks in a mixture of [Mdha(7)]- and [Dhb(7)]-congeners
      of [Asp(3)]MC-RR (4, 5), -RY (14, 15), and -LY (16, 17) in the samples from L.
      Steinsfjorden. This is also the first report of MC-RY-congeners outside of
      Africa, or in Planktothrix spp. Analysis of European crayfish (Astacus astacus)
      taken from L. Steinsfjorden revealed the presence of only trace levels of
      microcystins in the edible parts.

PMID- 23531155
TI  - Inhibition of ovine in vitro fertilization by anti-Prt antibody: hypothetical
      model for Prt/ZP interaction.
AB  - BACKGROUND: The impact of prion proteins in the rules that dictate biological
      reproduction is still poorly understood. Likewise, the role of prnt gene,
      encoding the prion-like protein testis specific (Prt), in ram reproductive
      physiology remains largely unknown. In this study, we assessed the effect of Prt
      in ovine fertilization by using an anti-Prt antibody (APPA) in fertilization
      medium incubated with spermatozoa and oocytes. Moreover, a computational model
      was constructed to infer how the results obtained could be related to a
      hypothetical role for Prt in sperm-zona pellucida (ZP) binding. METHODS: Mature
      ovine oocytes were transferred to fertilization medium alone (control) or
      supplemented with APPA, or pre-immune serum (CSerum). Oocytes were inseminated
      with ovine spermatozoa and after 18 h, presumptive zygotes (n=142) were fixed to
      evaluate fertilization rates or transferred (n=374) for embryo culture until D6
      7. Predicted ovine Prt tertiary structure was compared with data obtained by
      circular dichroism spectroscopy (CD) and a protein-protein computational docking
      model was estimated for a hypothetical Prt/ZP interaction. RESULTS: The
      fertilizing rate was lower (P=0.006) in APPA group (46.0+/-6.79%) when compared
      to control (78.5+/-7.47%) and CSerum (64.5+/-6.65%) groups. In addition, the
      cleavage rate was higher (P<0.0001) in control (44.1+/-4.15%) than in APPA group
      (19.7+/-4.22%). Prt CD spectroscopy showed a 22% alpha-helical structure in 30%
      (m/v) aqueous trifluoroethanol (TFE) and 17% alpha in 0.6% (m/v) TFE. The
      predominant alpha-helical secondary structure detected correlates with the
      predicted three dimensional structure for ovine Prt, which was subsequently used
      to test Prt/ZP docking. Computational analyses predicted a favorable Prt-binding
      activity towards ZP domains. CONCLUSIONS: Our data indicates that the presence of
      APPA reduces the number of fertilized oocytes and of cleaved embryos. Moreover,
      the CD analysis data reinforces the predicted ovine Prt trend towards an alpha
      helical structure. Predicted protein-protein docking suggests a possible
      interaction between Prt and ZP, thus supporting an important role for Prt in
      ovine fertilization.

PMID- 23531157
TI  - Electrochemically exfoliated graphene as solution-processable, highly conductive
      electrodes for organic electronics.
AB  - Solution-processable thin layer graphene is an intriguing nanomaterial with
      tremendous potential for electronic applications. In this work, we demonstrate
      that electrochemical exfoliation of graphite furnishes graphene sheets of high
      quality. The electrochemically exfoliated graphene (EG) contains a high yield
      (>80%) of one- to three-layer graphene flakes with high C/O ratio of 12.3 and low
      sheet resistance (4.8 kOmega/? for a single EG sheet). Due to the solution
      processability of EG, a vacuum filtration method in association with dry transfer
      is introduced to produce large-area and highly conductive graphene films on
      various substrates. Moreover, we demonstrate that the patterned EG can serve as
      high-performance source/drain electrodes for organic field-effect transistors.

PMID- 23531158
TI  - Rapid separation of developing Arabidopsis seeds from siliques for RNA or
      metabolite analysis.
AB  - BACKGROUND: Protein, starch and oil produced in plant seeds are major renewable
      sources of food, chemicals and biofuels. Developing Arabidopsis thaliana seeds
      are commonly utilized as a model for seed crop research. However, due to the very
      small size of Arabidopsis seeds efficient collection of large amounts of tissue
      for gene expression or metabolite analysis is very difficult and time consuming.
      RESULTS/CONCLUSIONS: Here we describe a method that allows very rapid separation
      and collection of large amounts of developing Arabidopsis seeds from their
      encapsulating silique tissue after flash freezing whole siliques in liquid
      nitrogen. The efficient popping open of the frozen siliques on dry ice and
      filtering the seeds away from the silique tissue with liquid nitrogen cooled
      funnels and sieves allows large amounts of developing seeds to be quickly
      isolated while remaining frozen. This method increases the speed of developing
      seed collection approximately 10 fold over methods which dissect individual
      siliques one at a time.

PMID- 23531160
TI  - Inflammation, serotonin and major depression.
AB  - The understanding of the neurobiological processes leading to major depressive
      disorder (MDD) is an active field of research in the scientific community. For
      years, the alteration of monoamine neurotransmission, in particular serotonin (5
      HT), has been considered the most significant pathophysiological mechanism of the
      disorder. However, biological data supporting the postulated MDD-related
      monoamine alterations have been inconclusive, and the use of monoaminergic
      antidepressants has not yielded the expected results. In the last few years, it
      has been demonstrated that inflammatory pathways have a significant role in the
      pathophysiology of MDD. According to the cytokine hypothesis, the disorder would
      be due to a stress-related increased production of cytokines, including
      interleukins, tumor necrosis factor- alpha and interferon- alpha and gamma .
      These, in turns, would cause the activation of the indoleamine 2,3 dioxygenase
      (IDO), with subsequent production of tryptophan (TRP) catabolites along the IDO
      pathway (TRYCATs) and decreased availability of TRP and 5-HT. Besides monoamines,
      other molecular mechanisms, as those within the inflammatory pathways, should be
      taken into account in the attempt to clarify the pathophysiology of MDD and to
      improve its treatment.

PMID- 23531161
TI  - Therapeutic prospects of PPARs in psychiatric disorders: a comprehensive review.
AB  - Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear
      receptors whose activation modulates the gene expression that underlies both the
      glucid-lipid and the inflammation pathways. While many PPARs agonists have been
      used for years as medication for metabolic disorders, an increasing attention is
      being currently dedicated to these drugs for inflammation-related pathologies.
      Within the psychiatric field, it has recently appeared that inflammatory
      processes are highly suspected in the pathophysiology of several important
      disorders, such as schizophrenia and mood disorders. By their anti-inflammatory
      properties, PPARs might have a disease-modifying action that could help in
      improving the outcome of patients. Furthermore, recent data suggest that PPARs
      could also modulate the expression of some neurotransmission factors. Therefore,
      PPARs may directly modify the information processing, and have a potential
      symptomatic action on several psychiatric disorders. At last, PPARs action of
      metabolic regulation could have a role on corrective or even preventive
      strategies against the metabolic adverse events that are commonly observed with
      some current psychiatric medications, notably antipsychotics. This triple
      potential action profile of PPARs modulators is investigated in this article,
      successively for schizophrenia spectrum disorders and mood disorders. Theoretical
      involvements of PPARs are also discussed for the treatment of Post- Traumatic
      Stress Disorder and Personality Disorders. At the time of the emerging concept of
      psychoneuroimmunology, PPARs open original therapeutic prospects for the
      psychiatric research.

PMID- 23531162
TI  - Nonoperative management for patients with grade IV blunt hepatic trauma.
AB  - INTRODUCTION: The treatment of complex liver injuries remains a challenge.
      Nonoperative treatment for such injuries is increasingly being adopted as the
      initial management strategy. We reviewed our experience, at a University teaching
      hospital, in the nonoperative management of grade IV liver injuries with the
      intent to evaluate failure rates; need for angioembolization and blood
      transfusions; and in-hospital mortality and complications. METHODS: This is a
      retrospective analysis conducted at a single large trauma centre in Brazil. All
      consecutive, hemodynamically stable, blunt trauma patients with grade IV hepatic
      injury, between 1996 and 2011, were analyzed. Demographics and baseline
      characteristics were recorded. Failure of nonoperative management was defined by
      the need for surgical intervention. Need for angioembolization and transfusions,
      in-hospital death, and complications were also assessed RESULTS: Eighteen
      patients with grade IV hepatic injury treated nonoperatively during the study
      period were included. The nonoperative treatment failed in only one patient
      (5.5%) who had refractory abdominal pain. However, no missed injuries and/or
      worsening of bleeding were observed during the operation. None of the patients
      died nor need angioembolization. No complications directly related to the liver
      were observed. Unrelated complications to the liver occurred in three patients
      (16.7%); one patient developed a tracheal stenosis (secondary to tracheal
      intubation); one had pleural effusion; and one developed an abscess in the
      pleural cavity. The hospital length of stay was on average 11.56 days.
      CONCLUSIONS: In our experience, nonoperative management of grade IV liver injury
      for stable blunt trauma patients is associated with high success rates without
      significant complications.

PMID- 23531166
TI  - Putrescine catabolism is a metabolic response to several stresses in Escherichia
      coli.
AB  - Genes whose products degrade arginine and ornithine, precursors of putrescine
      synthesis, are activated by either regulators of the nitrogen-regulated (Ntr)
      response or sigma(S) -RNA polymerase. To determine if dual control regulates a
      complete putrescine catabolic pathway, we examined expression of patA and patD,
      which specify the first two enzymes of one putrescine catabolic pathway. Assays
      of PatA (putrescine transaminase) activity and beta-galactosidase from cells with
      patA-lacZ transcriptional and translational fusions indicate dual control of patA
      transcription and putrescine-stimulated patA translation. Similar assays for PatD
      indicate that patD transcription required sigma(S) -RNA polymerase, and Nac, an
      Ntr regulator, enhanced the sigma(S) -dependent transcription. Since Nac
      activation via sigma(S) -RNA polymerase is without precedent, transcription with
      purified components was examined and the results confirmed this conclusion. This
      result indicates that the Ntr regulon can intrude into the sigma(S) regulon.
      Strains lacking both polyamine catabolic pathways have defective responses to
      oxidative stress, high temperature and a sublethal concentration of an
      antibiotic. These defects and the sigma(S) -dependent expression indicate that
      polyamine catabolism is a core metabolic response to stress.

PMID- 23531167
TI  - Using online adverts to increase the uptake of cervical screening amongst "real
      Eastenders": an opportunistic controlled trial.
AB  - BACKGROUND: Cervical screening uptake has increased as a result of occurrences of
      cervical cancer in TV 'soap operas' and in real life celebrities such as Jade
      Goody. Media analysis at the time of Jade Goody's death suggested the NHS did not
      take sufficient advantage of this opportunity to improve cervical screening
      rates. Google AdWords has been used to recruit and raise awareness of health but
      we were not aware of its use to supplement media events. METHODS: This was an
      opportunistic service evaluation to accompany a cervical cancer storyline in
      Eastenders (a TV 'soap opera'). We ran an AdWords campaign based on keywords such
      as 'Eastenders', and 'cervical cancer' in a one mile radius in East London,
      linked to one webpage giving details of 10 practices and other links on cervical
      cancer. We recorded costs of adverts and setting up the webpage. We used routine
      statistics from Tower Hamlets, City and Hackney, and Newham Primary Care Trusts
      (PCTs) of the number of smears, eligible populations, and coverage by practice by
      month from September 2010 to January 2012 to compare the ten intervention
      practices with controls. RESULTS: Eight people per day in the target area viewed
      the project webpage. The cost of setting up the website and running Google
      AdWords was L1320 or L1.88 per person viewing the webpage. Unlike Jade Goody's
      death, there was no major impact from the Eastenders' storyline on Google
      searches for cervical cancer. There was considerable monthly variation in the
      number of smear tests in the 3 PCTs. The AdWords campaign may have had some
      effect on smear rates but this showed, at best, a marginal statistical
      difference. Assuming a 'real' effect, the intervention may have resulted in 110
      'extra' women being screened but there was no change in coverage. CONCLUSIONS:
      Although the Eastenders storyline seemed to have no effect on interest in
      cervical cancer or screening, the AdWords campaign may have had some effect.
      Given the small scale exploratory nature of the study this was not statistically
      significant but the relatively modest cost of advertising suggests a larger study
      may be worthwhile. An outline of a possible study is described.

PMID- 23531168
TI  - Factors influencing a health promoting lifestyle in spouses of active duty
      military.
AB  - The purpose of this study was to understand the factors influencing the health
      promoting behaviors (HPBs) of military spouses. Pender's Health Promotion Model
      provided the theoretical framework guiding this study. One hundred twelve female
      spouses were surveyed regarding their perceived health status, perceived stress,
      self-efficacy, social support, and participation in HPBs. Perceived health
      status, self-efficacy, social support, and HPBs were positively related, whereas
      perceived stress was negatively related. Hierarchical multiple regression
      analysis showed perceived stress and social support to be predictive of an
      overall health promoting lifestyle (HPLPII), with the full model explaining 49.7%
      of the variance. 

PMID- 23531169
TI  - Prevention of ventilator-associated pneumonia in intensive care units: an
      international online survey.
AB  - BACKGROUND: On average 7% of patients admitted to intensive-care units (ICUs)
      suffer from a potentially preventable ventilator-associated pneumonia (VAP). Our
      objective was to survey attitudes and practices of ICUs doctors in the field of
      VAP prevention. METHODS: A questionnaire was made available online in 6 languages
      from April, 1st to September 1st, 2012 and disseminated through international and
      national ICU societies. We investigated reported practices as regards (1)
      established clinical guidelines for VAP prevention, and (2) measurement of
      process and outcomes, under the assumption "if you cannot measure it, you cannot
      improve it"; as well as attitudes towards the implementation of a measurement
      system. Weighted estimations for Europe were computed based on countries for
      which at least 10 completed replies were available, using total country
      population as a weight. Data from other countries were pooled together. Detailed
      country-specific results are presented in an online additional file. RESULTS: A
      total of 1730 replies were received from 77 countries; 1281 from 16 countries
      were used to compute weighted European estimates, as follows: care for intubated
      patients, combined with a measure of compliance to this guideline at least once a
      year, was reported by 57% of the respondents (95% CI: 54-60) for hand hygiene,
      28% (95% CI: 24-33) for systematic daily interruption of sedation and weaning
      protocol, and 27% (95%: 23-30) for oral care with chlorhexidine. Only 20% (95%
      CI: 17-22) were able to provide an estimation of outcome data (VAP rate) in their
      ICU, still 93% (95% CI: 91-94) agreed that "Monitoring of VAP-related measures
      stimulates quality improvement". Results for 449 respondents from 61 countries
      not included in the European estimates are broadly comparable. CONCLUSIONS: This
      study shows a low compliance with VAP prevention practices, as reported by ICU
      doctors in Europe and elsewhere, and identifies priorities for improvement.

PMID- 23531171
TI  - Determination of heterogeneous electron transfer and homogeneous
      comproportionation rate constants of tetracyanoquinodimethane using scanning
      electrochemical microscopy.
AB  - We report the use of scanning electrochemical microscopy (SECM) in determining
      the heterogeneous electron transfer and homogeneous comproportionation kinetics
      of tetracyanoquinodimethane (TCNQ) in acetonitrile at Pt tip UMEs (radius 12.5-1
      MUm). TCNQ undergoes two consecutive one-electron reductions with
      comproportionation occurring between TCNQ2-, the product of the second reduction,
      and bulk TCNQ to produce TCNQ-. A standard rate constant, k(1)(0) = 2.9 +/- 0.5
      cm/s, for the first reduction was determined by tip voltammetry with total
      positive feedback and a large Pt substrate. A comparatively smaller rate
      constant, k(2)(0) = 0.44 +/- 0.05 cm/s, for the second reduction was determined
      in the absence of comproportionation by tip voltammetry with the tip shielded
      from the bulk TCNQ solution by the TCNQ- diffusion layer of the large Pt
      substrate. A comproportionation rate constant, k(comp) = 1 * 10(6) M(-1) s(-1),
      was determined by tip pulse chronoamperometry at coaxially aligned tip and
      substrate UMEs of the same radius. Diffusion coefficients of the TCNQ species and
      standard potentials for the reductions were also determined. Experimental results
      were compared with 2D transient axisymmetric simulations and reported analytical
      equations.

PMID- 23531170
TI  - A computational study of systemic hydration in vocal fold collision.
AB  - Mechanical stresses develop within vocal fold (VF) soft tissues due to phonation
      associated vibration and collision. These stresses in turn affect the hydration
      of VF tissue and thus influence voice health. In this paper, high-fidelity
      numerical computations are described, taking into account fully 3D geometry,
      realistic tissue and air properties, and high-amplitude vibration and collision.
      A segregated solver approach is employed, using sophisticated commercial solvers
      for both the VF tissue and glottal airflow domains. The tissue viscoelastic
      properties were derived from a biphasic formulation. Two cases were considered,
      whereby the tissue viscoelastic properties corresponded to two different volume
      fractions of the fluid phase of the VF tissue. For each case, hydrostatic
      stresses occurring as a result of vibration and collision were investigated.
      Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF
      tissue was estimated from the hydrostatic stress gradient. Computed measures of
      overall VF dynamics (peak airflow velocity, magnitude of VF deformation,
      frequency of vibration and contact pressure) were well within the range of
      experimentally observed values. The VF motion leading to mechanical stresses
      within the VFs and their effect on the interstitial fluid flux is detailed. It is
      found that average deformation and vibration of VFs tend to increase the state of
      hydration of the VF tissue, whereas VF collision works to reduce hydration.

PMID- 23531172
TI  - Improving crop yield and water productivity by ecological sanitation and water
      harvesting in South Africa.
AB  - This study quantifies the potential effects of a set of technologies to address
      water and fertility constraints in rain-fed smallholder agriculture in South
      Africa, namely in situ water harvesting (WH), external WH, and ecological
      sanitation (Ecosan, fertilization with human urine). We used the Soil and Water
      Assessment Tool to model spatiotemporally differentiated effects on maize yield,
      river flow, evaporation, and transpiration. Ecosan met some of the plant nitrogen
      demands, which significantly increased maize yields by 12% and transpiration by
      2% on average across South Africa. In situ and external WH did not significantly
      affect the yield, transpiration or river flow on the South Africa scale. However,
      external WH more than doubled the yields for specific seasons and locations. WH
      particularly increased the lowest yields. Significant water and nutrient demands
      remained even with WH and Ecosan management. Additional fertility enhancements
      raised the yield levels but also the yield variability, whereas soil moisture
      enhancements improved the yield stability. Hence, coupled policies addressing
      both constraints will likely be most effective for improving food security.

PMID- 23531173
TI  - Conformational entropy of intrinsically disordered protein.
AB  - Intrinsically disordered proteins (IDPs), though lacking stable tertiary
      structures, are known to possess a certain amount of residual structure.
      Conformational disorder plays a crucial role through the conformational entropy
      in regulating protein-protein and protein-ligand interactions involved in
      signaling and regulation, and also modulates protein aggregation and
      amyloidogenesis associated with a number of human diseases. However, a direct and
      quantitative connection between the residual structure and the conformational
      entropy remains to be established. Here we show using a novel computational
      approach that the conformational entropy of amyloid-beta protein, an IDP whose
      aggregation is associated with Alzheimer's disease, is significantly correlated
      with the contents of the residual helical structure, beta-sheet structure, and
      salt-bridge network. Identification of the thermodynamically significant residual
      structure is of fundamental importance for a comprehensive understanding of the
      relationship between the functional conformational disorder and the protein
      activity regulation, and will also serve the thermodynamic basis of the amyloid
      polymorphism.

PMID- 23531175
TI  - Diverticular disease in younger patients--is it clinically more complicated and
      related to obesity?
AB  - AIM: The aims of this systematic review were to determine the presentations of
      diverticular disease in patients under 40 years of age and to assess whether
      obesity is an important factor. METHOD: The PubMed and EMBASE databases and the
      Cochrane Library were searched to identify all original articles published
      between 1990 and 2011 on diverticular disease severity in obese patients (body
      mass index of >= 30 kg/m(2) ) under 40 years of age. RESULTS: Twenty-three
      clinical case series (two of which were prospective) were identified plus two
      large aetiological population-based studies. These reported that young patients
      with diverticular disease were presenting more frequently, that diverticular
      disease in this age group was less likely to be complicated but that emergency
      operation rates were higher. The majority (63.1-96.5%) of patients under 40 years
      of age with diverticular disease were obese. CONCLUSION: The studies suggest that
      in the young, obese patient with lower abdominal pain, diverticulitis and
      appendicitis are included in the differential diagnosis. CT and/or laparoscopy
      should be considered where the diagnosis is in doubt.

PMID- 23531174
TI  - Comparison of vascular smooth muscle cells in canine great vessels.
AB  - BACKGROUND: Elucidating the histological characteristics of normal vascular
      smooth muscle cells (VSMCs) is important for understanding mechanisms of
      development, disease etiology and the remodeling and/or regeneration process of
      the vessel. However, knowledge regarding VSMCs is focused primarily on the
      artery. Although the characteristics of each great vessel are documented, few
      studies have examined VSMCs in parallel within each great vessel. The present
      study focused on comparing characteristics of canine VSMCs within the aorta (Ao),
      branch pulmonary artery (bPA), main pulmonary artery (mPA) and inferior vena cava
      (IVC), simultaneously. RESULTS: Western blot and immunohistochemistry were used
      to determine VSMC protein content for alpha smooth muscle actin (ASMA), calponin,
      myosin heavy chain (MHC) and its isozyme SM2, and non-muscle myosin heavy chain B
      (SMemb). Thickness and ratio of the VSMC layer were also measured. Expression
      levels of ASMA, calponin and SM2 significantly differed between vessels, except
      between mPA and either bPA, Ao and IVC vessels. Expression levels of MHC were
      significantly different in all vessels, whilst expression of SMemb was
      significantly different in the Ao compared with either bPA and mPA vessels. All
      vessels were significantly different with respect to total wall and VSMC layer
      thickness. The ratio between VSMC layer and total wall thickness was
      significantly different for each vessel, except between bPA and mPA vessels.
      Histological analysis of the IVC revealed that the VSMC layer does not line
      evenly and continuously through the long axis or transverse sections. With
      respect to the pulmonary artery, calponin was expressed to a greater extent in
      the mPA compared with the bPA (P < 0.01*). In contrast, MHC and SM2 were
      expressed to a greater extent in the bPA compared with the mPA (P < 0.01*).
      Differences in VSMC distribution indicate structural differences in the proximal
      and distal pulmonary artery bifurcation. CONCLUSION: Our results show that the
      VSMC expression pattern in each great vessel is unique and suggestive of the
      developmental differences between great vessels. We believe this study provides
      basic data for the pathology, etiology and regenerative capability of the
      vessels.

PMID- 23531176
TI  - Three cases of reverse pigment network on dermatoscopy with three distinctive
      histopathologic diagnoses.

PMID- 23531177
TI  - Disease risk curves.
AB  - Disease risk curves are simple graphical relationships between the probability of
      need for treatment and evidence related to risk factors. In the context of the
      present article, our focus is on factors related to the occurrence of disease in
      crops. Risk is the probability of adverse consequences; specifically in the
      present context it denotes the chance that disease will reach a threshold level
      at which crop protection measures can be justified. This article describes
      disease risk curves that arise when risk is modeled as a function of more than
      one risk factor, and when risk is modeled as a function of a single factor
      (specifically the level of disease at an early disease assessment). In both
      cases, disease risk curves serve as calibration curves that allow the accumulated
      evidence related to risk to be expressed on a probability scale. When risk is
      modeled as a function of the level of disease at an early disease assessment, the
      resulting disease risk curve provides a crop loss assessment model in which the
      downside is denominated in terms of risk rather than in terms of yield loss.

PMID- 23531178
TI  - The aging lymphatics become more mature.

PMID- 23531179
TI  - Aged lymphatic contractility: recent answers and new questions.
AB  - Abstract An overview is presented of recent findings related to biology of aging
      of the lymph transport system. The authors discuss recently obtained data on the
      aging-associated alterations of lymphatic contractility in thoracic duct and
      mesenteric lymphatic vessels; on comparisons of function of aged mesenteric
      lymphatic vessels in situ versus isolated specimens and important conclusions
      which arose from these studies; on aging-associated changes in functional status
      of mast cells located close to aged mesenteric lymphatic vessels; on evidence of
      presence of oxidative stress in aged lymphatic vessels and changes in arrangement
      of muscle cells in their walls. The authors conclude that future continuation of
      the research efforts in this area is necessary and will be able to provide not
      only novel fundamental knowledge on the biology of lymphatic aging, but also will
      create solid foundation for the subsequent developments of lymphatic-oriented
      therapeutic interventions in many diseases of the elderly.

PMID- 23531180
TI  - Systematic review of quality of life and patient reported outcomes in patients
      with oncologic related lower extremity lymphedema.
AB  - BACKGROUND: Lower limb lymphedema (LLL) is a common complication of cancer
      treatment. The disease is chronic and progressive with no cure. Although a common
      and significant source of morbidity, the impact of this condition on health
      related quality of life (HRQOL) has only recently been addressed. In effort to
      identify valid treatment strategies for LLL, we performed a systematic review,
      identifying studies describing HRQOL outcomes in patients with LLL secondary to
      cancer. METHODS AND RESULTS: Seven medical databases were searched to identify
      reports using validated Patient Reported Outcome (PRO) instruments on patients
      with cancer-related LLL. Studies were classified by levels of evidence set by the
      Agency for Healthcare Research and Quality (AHRQ) and evaluated using the
      Efficace criteria. 25 studies were identified, 6 met inclusion criteria. Levels
      of evidence included: no level I studies, level II (n=3), level III (n=1), and
      level 4 (n=2). 50% of studies were compliant with the Efficace criteria. 5 PRO
      HRQOL instruments were used, but only 1 was specific to cancer-related
      lymphedema. Treatment strategies assessed included complete decongestive
      physiotherapy (CDP), exercise, and compression bandaging. CDP yielded significant
      enhancements in HRQOL. CONCLUSIONS: There is a deficit in high quality studies
      for HRQOL in patients with LLL secondary to cancer. Furthermore, of the studies
      present, most did not conform to guidelines set for assessment of HRQOL, nor did
      they use lymphedema condition specific PRO instruments. New measures specific to
      assessing LLL are necessary to gain more accurate evaluation of how this
      debilitating disorder affects HRQOL.

PMID- 23531181
TI  - Is lymphatic endoglin expression a risk marker for breast cancer metastasis?
      Results of a pilot study.
AB  - BACKGROUND: Studies have identified endoglin as a biological marker that is
      overexpressed on the microvessels of certain solid cancers (breast, colorectal
      cancer, and head and neck squamous cell cancers). There is, at present, no
      immunohistochemical marker that can discriminate between lymph node-negative and
      or lymph node-positive breast cancer tissue. METHODS: The expression of endoglin
      was quantified by immunohistochemistry and assessment of microvessel density in
      53 surgical specimens. These were comprised of breast tumor tissue that had not
      spread to the regional lymph nodes (lymph node-negative breast tumor tissue: 20
      specimens), breast tumor tissue had spread to regional lymph nodes (lymph node
      positive breast tumor tissue: 21 specimens), and normal breast tissue as a
      control (12 specimens). RESULTS: Significant difference was observed between the
      expression of endoglin on microvessels of lymph node-negative and lymph node
      positive breast cancer tissue (p<0.05). This significant difference was shown to
      be due to endoglin expression on lymphatic vessels (p<0.02), rather than on blood
      vessels (p>0.05). CONCLUSIONS: These findings are the first to suggest that
      endoglin expression on breast tumor lymphatic vessels may have diagnostic
      potential as a discriminator between lymph node-negative and lymph node-positive
      breast cancer. Further studies would be required to confirm this.

PMID- 23531182
TI  - Characterization of cells expressing lymphatic marker LYVE-1 in macaque large
      intestine during simian immunodeficiency virus infection identifies a large
      population of nonvascular LYVE-1(+)/DC-SIGN(+) cells.
AB  - Abstract LYVE-1 is a marker expressed by lymphatic endothelial cells (LECs) that
      line the lymphatic endothelium. Through studies designed to examine potential
      changes in expression of LYVE-1 in cynomolgus macaque colon tissues during the
      course of simian immunodeficiency virus (SIV) infection, we discovered that LYVE
      1 was expressed by heterogenous populations of cells. As revealed by in situ
      hybridization (ISH), LYVE-1 mRNA levels in colon were decreased in macaques with
      AIDS compared with acutely infected or uninfected macaques. In the submucosal
      layer of the colon, approximately half of the LYVE-1-expressing cells co
      expressed the dendritic cell (DC) marker, DC-SIGN/CD209, and this percentage did
      not change appreciably during infection. Subsets of cells expressing LYVE-1 also
      co-expressed macrophage markers, such as CD68 and the macrophage mannose receptor
      (MMR)/CD206, in both the colon and lymph nodes. LECs, DCs, and macrophages that
      co-expressed LYVE-1 were observed in colon and lymph node from uninfected,
      healthy animals as well as in tissues with SIV-driven inflammation. These
      findings provide further definition of the phenotypic overlap between LECs and
      antigen presenting cells, reveal the heterogeneity within the population of cells
      expressing the lymphatic marker LYVE-1, and show that SIV modulates this
      population of cells in a mucosal surface across which the virus is acquired.

PMID- 23531183
TI  - Lymphatic muscle cells in rat mesenteric lymphatic vessels of various ages.
AB  - BACKGROUND: Recent studies on aging-associated changes in mesenteric lymph flow
      in situ demonstrated predominance of the severe negative chronotropic effect of
      aging on the contractility of aged mesenteric lymphatic vessels (MLV). At the
      same time, contraction amplitude of the aged vessels was only slightly diminished
      by aging and can be rapidly stimulated within 5-15 minutes. However, the detailed
      quantitative evaluation of potential aging-associated changes in muscle cells
      investiture in MLV has never been performed. METHODS AND RESULTS: In this study
      we, for the first time, performed detailed evaluation of muscle cells investiture
      in MLV in reference to the position of lymphatic valve in different zones of
      lymphangion within various age groups (3-mo, 9-mo and 24-mo Fischer-344 rats).
      Using visual and quantitative analyses of the images of MLV immunohistochemically
      labeled for actin, we confirmed that the zones located close upstream (pre-valve
      zones) and above lymphatic valves (valve zones) possess the lowest investiture of
      lymphatic muscle cells. Most of the high muscle cells investiture zones exist
      downstream to the lymphatic valve (post-valve zones). The muscle cells
      investiture of these zones is not affected by aging, while pre-valve and valve
      zones demonstrate significant aging-associated decrease in muscle cells
      investiture. CONCLUSIONS: The low muscle cells investiture zones in lymphatic
      vessels consist of predominantly longitudinally oriented muscle cells which are
      positioned in pre-valve and valve zones and connect adjacent lymphangions. These
      cells may provide important functional impact on the biomechanics of the
      lymphatic valve gating and electrical coupling between lymphangions, while their
      aging-associated changes may delimit adaptive reserves of aged lymphatic vessels.

PMID- 23531184
TI  - Isolated primary lymphedema tarda of the upper limb.
AB  - Primary lymphedema tarda is considered as a congenital disease with late
      presentation. Primary lymphedema tarda usually affects lower limbs, and primary
      lymphedema tarda of the upper limbs usually accompanies lower limb lymphedema. In
      the current case report, we present an 80-year-old male patient with isolated
      left upper limb swelling that lymphoscintigraphy imaging proved to be lymphedema.

PMID- 23531187
TI  - Potential repurposing of oncology drugs for the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of neurodegenerative dementia,
      affecting about 30 million people worldwide. Despite recent advances in
      understanding its molecular pathology, no mechanism-based drugs are currently
      available that can halt the progression of AD. Because amyloid-beta-peptide
      (Abeta), a primary component of senile plaques, is thought to be a central
      pathogenic culprit, several disease-modifying therapies are being developed,
      including inhibitors of Abeta-producing proteases and immunotherapies with anti
      Abeta antibodies. Drug repositioning or repurposing is regarded as a
      complementary and reasonable approach to identify new drug candidates for AD.
      This commentary will discuss the clinical relevance of an attractive candidate
      compound reported in a recent paper by Hayes et al. (BMC Medicine 2013) as well
      as perspectives regarding the possible repositioning of oncology drugs for the
      treatment of AD. See related research article here
      http://www.biomedcentral.com/1741-7015/11/81.

PMID- 23531188
TI  - Permissive hypotension does not reduce regional organ perfusion compared to
      normotensive resuscitation: animal study with fluorescent microspheres.
AB  - INTRODUCTION: The objective of this study was to investigate regional organ
      perfusion acutely following uncontrolled hemorrhage in an animal model that
      simulates a penetrating vascular injury and accounts for prehospital times in
      urban trauma. We set forth to determine if hypotensive resuscitation (permissive
      hypotension) would result in equivalent organ perfusion compared to normotensive
      resuscitation. METHODS: Twenty four (n=24) male rats randomized to 4 groups:
      Sham, No Fluid (NF), Permissive Hypotension (PH) (60% of baseline mean arterial
      pressure - MAP), Normotensive Resuscitation (NBP). Uncontrolled hemorrhage caused
      by a standardised injury to the abdominal aorta; MAP was monitored continuously
      and lactated Ringer's was infused. Fluorimeter readings of regional blood flow of
      the brain, heart, lung, kidney, liver, and bowel were obtained at baseline and 85
      minutes after hemorrhage, as well as, cardiac output, lactic acid, and laboratory
      tests; intra-abdominal blood loss was assessed. Analysis of variance was used for
      comparison. RESULTS: Intra-abdominal blood loss was higher in NBP group, as well
      as, lower hematocrit and hemoglobin levels. No statistical differences in
      perfusion of any organ between PH and NBP groups. No statistical difference in
      cardiac output between PH and NBP groups, as well as, in lactic acid levels
      between PH and NBP. NF group had significantly higher lactic acidosis and had
      significantly lower organ perfusion. CONCLUSIONS: Hypotensive resuscitation
      causes less intra-abdominal bleeding than normotensive resuscitation and
      concurrently maintains equivalent organ perfusion. No fluid resuscitation reduces
      intra-abdominal bleeding but also significantly reduces organ perfusion.

PMID- 23531189
TI  - Characterization of spontaneous collagen fibrillogenesis in a cell-free and
      tension-free environment.
AB  - The collagen fibril packing that forms threads and bundles is poorly defined,
      despite the fact that it is important for distinct aspects of the adventitial and
      reticular dermis. The present study explored an in vitro fibrillogenesis model
      using the property of heat polymerization. The process was performed on glass
      slides with mixtures of collagen I and III, and the material was viewed by
      scanning electron microscopy. In all instances, collagen I and III formed fibrils
      with regular sizes. The formation of threads was influenced by the relative
      proportions of collagen I and III; increasing the relative proportion of collagen
      I resulted in the formation of threads showing increasing variations in
      thickness. These findings are in line with the differential presentation and
      compositions of the different parts of the dermis. The possible interventions of
      stromal cells and of other macromoleules of the extracellular matrix were not
      considered in this study.

PMID- 23531190
TI  - Comparing the effectiveness of a multi-component weight loss intervention in
      adults with and without intellectual disabilities.
AB  - BACKGROUND: The prevalence of obesity in adults with intellectual disabilities
      (ID) is rising, although the evidence base for its treatment in this population
      group is minimal. Weight management interventions that are accessible to adults
      with ID will reduce the inequalities that they frequently experience in health
      services. This short report compared the effectiveness of weight management in
      those with and without ID who completed nine sessions of a multi-component weight
      management programme. METHODS: TAKE 5 is a 16-week multi-component weight
      management intervention for adults with ID and obesity [body mass index (BMI)
      >=30 kg m(-2) ]. This intervention is an adaption of the weight management
      programme provided by the Glasgow & Clyde Weight Management Service (GCWMS) for
      adults without ID and obesity (National Health Service based). Fifty-two
      participants of the TAKE 5 programme were individually matched by baseline
      characteristics (sex, age and BMI) with two participants without ID of the GCWMS
      programme. Comparisons in terms of weight and BMI change and rate of weight loss
      were made for those who attended all nine sessions. RESULTS: There were no
      significant differences between the groups in the amount of weight loss (median: 
      3.6 versus -3.8 kg, respectively, P = 0.4), change in BMI (median: -1.5 versus 
      1.4 kg m(-2) , P = 0.9), success of achieving 5% weight loss (41.3% versus 36.8%,
      P = 0.9) and rate of weight loss across the 16-week intervention. CONCLUSIONS: A
      multi-component weight loss intervention can be equally effective for adults with
      and without ID and obesity.

PMID- 23531191
TI  - Microbubble-assisted p53, RB, and p130 gene transfer in combination with
      radiation therapy in prostate cancer.
AB  - Combining radiation therapy and direct intratumoral (IT) injection of adenoviral
      vectors has been explored as a means to enhance the therapeutic potential of gene
      transfer. A major challenge for gene transfer is systemic delivery of nucleic
      acids directly into an affected tissue. Ultrasound (US) contrast agents
      (microbubbles) are viable candidates to enhance targeted delivery of systemically
      administered genes. Here we show that p53, pRB, and p130 gene transfer mediated
      by US cavitation of microbubbles at the tumor site resulted in targeted gene
      transduction and increased reduction in tumor growth compared to DU-145 prostate
      cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation
      alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed
      significant reduction in tumor volume compared to Ad.p130 treated tumors
      (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined
      with external beam radiation resulted in the most profound tumor reduction in DU
      145 xenografted nude mice (p<0.05) compared to radiation alone. These findings
      highlight the potential therapeutic applications of this novel image-guided gene
      transfer technology in combination with external beam radiation for prostate
      cancer patients with therapy resistant disease.

PMID- 23531192
TI  - Progress and prospects: the use of 3D spheroid model as a relevant way to study
      and optimize DNA electrotransfer.
AB  - The use of electrotransfer to deliver therapeutic agents such as cytotoxic drugs
      and nucleic acids to cells and tissues has been successfully developed over the
      last decade. This strategy is promising for the systemic secretion of therapeutic
      proteins, vaccination and gene therapy. The safe and efficient use of this
      physical method for clinical purposes requires knowledge of the mechanisms
      underlying the DNA electrotransfer and expression phenomena. Despite the fact
      that the pioneering work on plasmid DNA electrotransfer to cells was initiated 30
      years ago, many of the underlying mechanisms remain elucidated. While efficient
      in vitro, the method faces a lack of efficiency in packed tissues. Until now, the
      great majority of studies have been performed on cells in 2D cultures in Petri
      dishes or in suspension. However, these studies cannot get access to the tissue
      specific architecture and organization present in 3D living tissues. In this
      context, 3D cell culture models are more relevant concerning in vivo cell
      organization since cell-cell contacts are present as well as extracellular
      matrix. The aim of this review is to describe the relevance of using spheroid as
      a model to address and improve the electrotransfer processes.

PMID- 23531193
TI  - Impact of PLK-1 silencing on endothelial cells and cancer cells of diverse
      histological origin.
AB  - The main goal of this work was to assess in vitro the potential of Polo-like
      kinase gene (PLK-1) as a molecular target within the tumor microenvironment,
      namely in both cancer cells of tumors of different histological origin and
      endothelial cells from angiogenic blood vessels, upon silencing with anti-PLK-1
      siRNA. In addition, the effect of Plk-1 downregulation on the cancer cells
      chemosensitization to paclitaxel was further assessed. Downregulation of Plk-1
      reduced cancer cells viability from 40 to 85% and up to 59% in endothelial cells.
      Regarding the latter, it compromised their ability to form new tube-like
      structures, decreasing the formation of network projections up to 46%. This
      suggested for the first time, PLK-1 as a valuable angiogenic molecular target. In
      combination with paclitaxel, anti-PLK-1 siRNA chemosensitized non-small cell lung
      cancer (NSCLC) and prostate carcinoma cell lines, leading up to a 2-fold increase
      in the drug cytotoxic effect. Moreover, the sequential incubation of anti-PLK-1
      siRNA and paclitaxel led to a decrease in the IC50 of the latter up to 2.7- and
      4.1-fold, in A-549 and PC-3 cells, respectively. The combination of anti-PLK-1
      siRNA with paclitaxel led to cell cycle arrest, increasing the number of cells at
      the G2/M and S phases to 1.5 and 1.3-fold in PC-3 cells, and to 1.6 and 1.4-fold
      in A-549 cells, respectively. Overall, it has been demonstrated that PLK-1
      silencing with siRNA can impact multiple cellular players of tumor
      aggressiveness, thus enabling the opportunity to interfere with different
      hallmarks of cancer, in tumors with diverse histological origin.

PMID- 23531194
TI  - Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.
AB  - Economic evaluations of health interventions pose a particular challenge for
      reporting. There is also a need to consolidate and update existing guidelines and
      promote their use in a user friendly manner. The Consolidated Health Economic
      Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate
      and update previous health economic evaluation guidelines efforts into one
      current, useful reporting guidance. The primary audiences for the CHEERS
      statement are researchers reporting economic evaluations and the editors and peer
      reviewers assessing them for publication.The need for new reporting guidance was
      identified by a survey of medical editors. A list of possible items based on a
      systematic review was created. A two round, modified Delphi panel consisting of
      representatives from academia, clinical practice, industry, government, and the
      editorial community was conducted. Out of 44 candidate items, 24 items and
      accompanying recommendations were developed. The recommendations are contained in
      a user friendly, 24 item checklist. A copy of the statement, accompanying
      checklist, and this report can be found on the ISPOR Health Economic Evaluations
      Publication Guidelines Task Force website
      (http://www.ispor.org/TaskForces/EconomicPubGuidelines.asp).We hope CHEERS will
      lead to better reporting, and ultimately, better health decisions. To facilitate
      dissemination and uptake, the CHEERS statement is being co-published across 10
      health economics and medical journals. We encourage other journals and groups, to
      endorse CHEERS. The author team plans to review the checklist for an update in
      five years.

PMID- 23531195
TI  - Awareness of headache and of National Headache Society activities among primary
      care physicians - a qualitative study.
AB  - BACKGROUND: Headache is one of the most common symptoms in primary care. To
      improve the quality of headache diagnosis and management with the largest
      possible benefit for the general population, headache and pain societies around
      the world have recently been devoting more attention to headache in primary
      care.The aim of the study was to investigate the potential contribution that
      national societies can make toward raising the awareness of primary headaches in
      general practice. FINDINGS: In a qualitative telephone survey, targeting primary
      care practices (PCP), we asked about the frequency of headache patients in their
      practices and inquired about their treatment and referral strategies.A total of
      1000 telephone interviews with PCP have been conducted. Three-hundred and fifty
      physicians have been directly interviewed, 95% of them see headache patients
      every week, 23% daily. Direct MRI referral is done by 84%. Sixty-two per cent of
      the physicians knew the Swiss headache society, 73% were interested in further
      education about headaches. CONCLUSION: The survey yielded information about the
      physicians' awareness of the Swiss Headache Society and its activities, and about
      their desire for continuing education in the area of headache. National headache
      societies should work to improve the cooperation between headache specialists and
      PCP, aiming for a better care for our patients with headache.

PMID- 23531196
TI  - Respiratory failure in a patient with dermatomyositis.
AB  - Since its original description in 1956 the association between interstitial lung
      disease and polymyositis (PM) and dermatomyositis (DM) has become well
      established. Interstitial lung disease (ILD) can be a significant complication in
      rheumatic diseases (RDs). Although most patients with RD do not develop
      clinically evident ILD, these systemic autoimmune disorders are estimated to be
      responsible for approximately 25% of all ILD deaths and 2% of deaths due to all
      respiratory causes. Radiologic abnormalities in DM are characterized by a high
      incidence of airspace consolidation. Non-Specific Interstitial Pneumonia (NSIP)
      is the most common form of lung disease, with a frequency in biopsies 4-fold
      greater than that of Usual Interstitial Pneumonia (UIP) in PM and a slightly
      smaller predominance in DM.We report a case of a female patient, 57 years old, no
      former smoker, whose clinical history was onset in November 2008 with asthenia
      with muscle and osteoarticular pain especially located in the upper limbs and
      then also expanded to the lower limbs. The EMG was compatible with
      dermatomyositis in the acute phase. The patient received therapy with steroids
      and tacrolimus, also making several rounds of treatment with immunoglobulin.
      Given the recurrence of myositis in association with signs of poorly controlled
      interstitial lung disease, immunosuppressive therapy with Rituximab was
      administered. The Computed Tomography (CT) scans showed "bronchiectasis and
      traction bronchiolectasis, hypodense areas consistent with the phenomena of air
      trapping. The pattern of interstitial lung disease with fibrotic evolution seems
      consistent with NSIP.The arterial blood gas analysis showed a pattern of hypoxic
      hypercapnic respiratory failure (pH: 7,34, PaO2: 67 mmHg; PaCO2: 55 mmHg).As a
      result of an episode of marked desaturation unresponsive to supplemental oxygen
      at high flows we proceeded to noninvasive mechanical ventilation with Helmet for
      24 hours/24. This ventilatory support was maintained for a week, with resolution
      of the respiratory failure.In this brief case report we want to highlight various
      pulmonary complications as a result of dermatomyositis. The progression of
      respiratory complications may also lead to a situation of respiratory failure, as
      in our patient, and require a noninvasive ventilatory treatment.

PMID- 23531197
TI  - Spectra and dynamics in the B800 antenna: comparing hierarchical equations,
      Redfield and Forster theories.
AB  - We model the spectra (absorption and circular dichroism) and excitation dynamics
      in the B800 ring of the LH2 antenna complex from Rs. molischianum using different
      theoretical approaches, i.e., Forster theory, standard and modified versions of
      the Redfield theory, and the more versatile nonperturbative approach based on
      hierarchically coupled equations for the reduced density operator. We demonstrate
      that, although excitations in the B800 ring are localized due to disorder,
      thermal effects, and phonons, there are still sizable excitonic effects producing
      shift, narrowing, and asymmetry of the spectra. Moreover, the excitation dynamics
      reveals the presence of long-lived (up to 1 ps) non-oscillatory coherences
      between the exciton states maintained due to nonsecular population-to-coherence
      transfers. The sub-ps decay of the coherences is followed by slow motion of the
      excitation around the ring, producing equilibration of the site populations with
      a time constant of about 3-4 ps, which is slower than the B800 -> B850 transfer.
      The exact solution obtained with the hierarchical equations is compared with
      other approaches, thus illustrating limitations of the Forster and Redfield
      pictures. 

PMID- 23531198
TI  - Measurement of antioxidant activity and antioxidant compounds under versatile
      extraction conditions: I. the immuno-biochemical antioxidant properties of sweet
      cherry (Prunus avium) extracts.
AB  - Previously, we have meticulously examined the efficacy of the measurable
      antimicrobial activity of sweet cherry (Prunus avium) extracts on a wide spectrum
      of gram-positive and gram-negative bacteria, in addition to the fungus, Candida
      albicans, a priori. In order to further understand the biochemical constituents
      and antioxidant activities of a variety of extracts of sweet cherries,
      antioxidant compounds of immunological significance, including L-ascorbic acid
      (vitamin C), phenols, flavonoids, and anthocyanins, and the total antioxidant
      (free radical scavenging) activity were simultaneously measured under varying and
      versatile extraction conditions (mild heating [5, 10 and 20 min.], and brief
      microwave exposure [1, 2 and 5 min.]) for a variety of extracts: i) whole juice
      extracts (WJE), ii) methanol-extracted juice (MEJ), iii) ddH2O-extracted pomace
      (dPOM), and iv) methanol-extracted pomace (mPOM). The antioxidant activity under
      the versatile extraction conditions adopted in this study was conspicuously
      reduced, such that the % inhibition against 2,2- diphenyl-1-picrylhydrazyl (DPPH)
      followed an inverse, negative correlational trendline. Moreover, ascorbic acid
      content was not affected with mild to prolonged heating or microwave exposure,
      except tangibly with dPOM and mPOM. The total phenols content assessed showed no
      significant variations, as compared with control extracts. In a manner similar to
      ascorbic acid, total flavonoids were mildly reduced under varying conditions, an
      effect mimicked to a certain extent with anthocyanins. Assessment of extraction
      means as compared with WJE revealed sharp decrease in the antioxidant activity
      for dPOM and mPOM, significant increase in L-ascorbic acid, total phenol, and
      flavonoid contents for MEJ, dPOM, and mPOM, and mild decrease in anthocyanin
      contents for dPOM and mPOM. These results confirm the measurable antioxidant
      activities and contents of P. avium extracts under versatile conditions of mild
      exposure, an effect bearing significant biochemical properties of a variety of
      extraction methods. Further studies are currently investigating the effect of
      specific antioxidants of P. avium on microbial growth in vitro per se. Since many
      of the aforementioned molecules hold immunobiochemical constituencies,
      antioxidant compounds in sweet cherries may have putative anti-inflammatory
      potential in medicinal chemistry, corroborating the observation of
      regulating/attenuating the growth of microorganisms of medical importance in
      vitro.

PMID- 23531199
TI  - Microstructural residual stress in particle-filled dental composite.
AB  - The main goal of this study is to develop a micromechanical model of a particle
      filled dental composite focused on the residual stress (RS) field developed
      during the curing process in its microstructure. A finite element model of a
      representative volume element of filler and resin was developed, and volumetric
      shrinkage was simulated during the curing process. Four material models (von
      Mises plasticity model, Drucker-Prager plasticity model, von Mises plasticity
      model with stress relaxation and Drucker-Prager plasticity with stress
      relaxation) of the polymer resin were built to assess the influence of the
      material model on the resulting internal stress. The relationship between the
      curing process and the magnitude of the stress components will be described, and
      an analysis of the post-curing state of the material in particular microstructure
      locations will be conducted in this study. Obtained RS is comparable to the
      stresses developed in the material under the external load. The substantial
      dependence on the choice of material model for resin is to be observed, and the
      suitability of particular models is discussed. 

PMID- 23531200
TI  - Thromboelastometry in veal calves to detect hemostatic variations caused by low
      doses of dexamethasone treatment.
AB  - BACKGROUND: The illegal administration of hormones, steroids, beta-agonists and
      other anabolic agents to productive livestock in the European Union continues,
      despite the long-term ban on their use and despite the measures provided under
      the directives to monitor certain substances and residues thereof in the interest
      of protecting consumer health and animal wellbeing. Often administered in low
      doses in the form of a drug cocktail, these compounds escape detection by common
      analytical techniques. The aim of this study was to determine whether low-dose
      dexamethasone administration (0.4 mg orally per day, for 20 days) in white-meat
      calves produced variations in blood coagulation, as measured by
      thromboelastometry. A second aim was to determine whether such variations could
      be valid in detecting illicit low-dose dexamethasone treatment. RESULTS: The
      study population was 42 Friesian calves kept under controlled conditions until 6
      months of age. The calves were subdivided into 2 groups: a control group (group
      A, n = 28) and a group treated with dexamethasone (group B, n = 14) for 20 days
      beginning at 5 months of age. When compared against the age-matched control
      group, the dexamethasone-treated calves showed a significant increase in alpha
      angle, maximum clot firmness and a significant decrease in clot formation time on
      all thromboelastometric profiles (P < 0.05). The clotting time was significantly
      decreased on the in-TEM(r) profile but increased on the ex-TEM(r) and fib-TEM(r)
      profiles (P <0.05). The Receiver Operating Characteristic curves, plotted for the
      Maximum Clot Elasticity (MCE), had a cut-off value >= 488.23 mm for in-TEM(r) MCE
      [Se 85.7%, (95% CI 57.2-98.2); Sp 100% 96.43% (95% CI 81.7-99.9] and a cut-off
      value >= 63.94 mm for fib-TEM(r) MCE [Se 92.8 (95% CI 66.1-99.8); Sp 89.3% (95%
      CI 71.8-97.7)]. In order to increase the sensitivity of the test two parameters
      (in-TEM(r) and fib-TEM(r) MCE) were used as two parallel tests; subsequently, the
      sensitivity rose to a point value of 99% (95% CI 85.4-99.9). CONCLUSIONS:
      Thromboelastometry identified a state of hypercoagulability in the dexamethasone
      treated subjects. Furthemore, the results of this preliminary study suggest that
      TEM may be useful in the detection of illicit low-dose dexamethasone treatment.

PMID- 23531201
TI  - Isoelectric focusing in continuously tapered fused silica capillary prepared by
      etching with supercritical water.
AB  - This communication indicates the potential of etching with sub- and/or
      supercritical water for reproducible preparation of fused-silica capillaries with
      tapered geometry suitable for capillary isoelectric focusing (CIEF) with
      electroosmotic displacement. The etching procedure provided a single-piece
      combination of the tapered separation space with a cylindrical connection of the
      detection window to the electrode vial. Selected proteins and colored pI markers
      were used as model analytes. A comparison with conventional cylindrical capillary
      under comparable applied voltage and analysis time was made, and the resultant
      peaks were compared in terms of peak resolution under optimized conditions. In
      CIEF carried out in a tapered capillary with the inlet cross-section three times
      larger than the cross-section at the detection window, three to four times higher
      resolutions of corresponding peak pairs were obtained. The method described opens
      the way to increase the number of separable compounds without resorting to
      excessively high voltage.

PMID- 23531202
TI  - Impact of diuretic therapy-associated electrolyte disorders present on admission
      to the emergency department: a cross-sectional analysis.
AB  - BACKGROUND: Diuretics are among the most commonly prescribed medications and, due
      to their mechanisms of action, electrolyte disorders are common side effects of
      their use. In the present work we investigated the associations between diuretics
      being taken and the prevalence of electrolyte disorders on admission as well as
      the impact of electrolyte disorders on patient outcome. METHODS: In this cross
      sectional analysis, all patients presenting between 1 January 2010 and 31
      December 2011 to the emergency room (ER) of the Inselspital, University Hospital
      Bern, Switzerland were included. Data on diuretic medication, baseline
      characteristics and laboratory data including electrolytes and renal function
      parameters were obtained from all patients. A multivariable logistic regression
      model was performed to assess the impact of factors on electrolyte disorders and
      patient outcome. RESULTS: A total of 8.5% of patients presenting to the ER used
      one diuretic, 2.5% two, and 0.4% three or four. In all, 4% had hyponatremia on
      admission and 12% hypernatremia. Hypokalemia was present in 11% and hyperkalemia
      in 4%. All forms of dysnatremia and dyskalemia were more common in patients
      taking diuretics. Loop diuretics were an independent risk factor for
      hypernatremia and hypokalemia, while thiazide diuretics were associated with the
      presence of hyponatremia and hypokalemia. In the Cox regression model, all forms
      of dysnatremia and dyskalemia were independent risk factors for in hospital
      mortality. CONCLUSIONS: Existing diuretic treatment on admission to the ER was
      associated with an increased prevalence of electrolyte disorders. Diuretic
      therapy itself and disorders of serum sodium and potassium were risk factors for
      an adverse outcome.

PMID- 23531203
TI  - Mean central corneal thickness and corneal power measurements in pigmented and
      white rabbits using Visante optical coherence tomography and ATLAS corneal
      topography.
AB  - OBJECTIVE: To document central corneal thickness (CCT) and power measurements in
      pigmented and white rabbits using Visante anterior segment optical coherence
      tomography (AS-OCT) and the Humphrey ATLAS Corneal Topography System (HACTS).
      ANIMAL STUDIED: Fourteen female rabbits (seven pigmented and seven white rabbits)
      were involved in this study. PROCEDURE: Twenty-eight eyes underwent AS-OCT and
      HACTS examination. Central corneal thickness, corneal power in the steepest and
      flattest meridians, astigmatism, pupil diameter (PD), and white-to-white (WTW)
      were calculated. RESULTS: The CCT was 390 +/- 14.2 and 373 +/- 7.2 MUm for
      pigmented and white rabbits, respectively. The CCT values showed statistical
      difference between the two breeds (P = 0.017). The corneal power in the steepest
      meridian was 44.6 +/- 1.9 Diopter (D) in pigmented rabbits and 47.8 +/- 1.5 D in
      white rabbits. The corneal power in the flattest meridian was 44.0 +/- 2.1 D in
      pigmented rabbits and 47.4 +/- 1.5 D in white rabbits. The astigmatism, PD, and
      WTW values were 0.6 +/- 0.22 D, 7.9 +/- 0.9, and 14.5 +/- 0.1 mm in pigmented
      rabbits, respectively. The corresponding values in white rabbits were 0.4 +/-
      0.23 D, 7.5 +/- 0.5, and 13.5 +/- 0.2 mm. There was a statistically significant
      difference in corneal power in the steepest and flattest meridians and for WTW.
      No such difference was observed for astigmatism or PD between them. CONCLUSIONS:
      Differences exist in the CCT, corneal power, and WTW between 5-month-old
      pigmented and white rabbits. Such difference should be considered when designing
      cornea-related experiments in rabbits.

PMID- 23531204
TI  - Effects of impoverished environmental conditions on working memory performance.
AB  - This cross-cultural study investigates the impact of background experience on
      four verbal and visuo-spatial working memory (WM) tasks. A total of 84 children
      from low-income families were recruited from the following groups: (1) Portuguese
      immigrant children from Luxembourg impoverished in terms of language experience;
      (2) Brazilian children deprived in terms of scholastic background; (3) Portuguese
      children from Portugal with no disadvantage in either scholastic or language
      background. Children were matched on age, gender, fluid intelligence, and
      socioeconomic status and completed four simple and complex span tasks of WM and a
      vocabulary measure. Results indicate that, despite large differences in their
      backgrounds and language abilities, the groups exhibited comparable performance
      on the visuo-spatial tasks dot matrix and odd-one-out and on the verbal simple
      span task digit recall. Group differences emerged on the verbal complex span task
      counting recall with children from Luxembourg and Portugal outperforming children
      from disadvantaged schools in Brazil. The study suggests that whereas
      contributions of prior knowledge to digit span, dot matrix, and odd-one-out are
      likely to be minimal, background experience can affect performance on counting
      recall. Implications for testing WM capacity in children growing up in poverty
      are discussed. 

PMID- 23531205
TI  - Hepatic autophagy is differentially regulated in periportal and pericentral zones
      - a general mechanism relevant for other tissues?
AB  - BACKGROUND: Liver zonation, the fact that metabolic pathways are spatially
      separated along the liver sinusoids, is fundamental for proper functioning of
      this organ. For example, glutamine synthesis from glutamate and ammonia is
      localized pericentrally in only 7% of the hepatocytes concentrically arranged
      around the central veins. Recently, we found that FOXO transcription factors lead
      to upregulation of glutamine synthetase expression inducing autophagy via
      increasing glutamine production. Since in liver this mechanism can only be
      functioning in the pericentral zone it remains unclear how autophagy might be
      regulated in the rest of liver parenchyma. PRESENTATION OF THE HYPOTHESIS: We
      hypothesize that the regulation of autophagy by glutamine in liver is zonated. In
      the periportal zone, autophagy is inhibited by low intracellular glutamine but
      high essential amino acids, while in the pericentral zone it is stimulated by
      high intracellular glutamine. This zonation may be controlled by the Wnt and
      Hedgehog signalling pathways through reciprocal influence on the expression of
      amino acid transporters and metabolic enzymes in the different zones of the
      parenchyma. TESTING THE HYPOTHESIS: The hypothesis can be tested in transgenic
      mice with conditional hepatocyte-specific modulation of Wnt and Hedgehog
      signalling. Isolated periportal and pericentral hepatocyte populations allow for
      determining the different activities of autophagy and its regulating mechanisms
      in different zones of the parenchyma. IMPLICATIONS OF THE HYPOTHESIS: Zonation of
      the regulation of autophagy may allow adapting the extent of the proteolytic
      breakdown of proteins and organelles to different physiological needs in
      different zones of liver parenchyma. In this manner metabolic functions can be
      supported in one zone, for example maintenance of blood glucose levels during
      starvation which is a periportal issue, while simultaneously preventing cytotoxic
      events in the opposite zone. Likewise, lipid metabolism can be differentially
      influenced by uncoupling periportal lipophagy from pericentral breakdown of
      peroxisomes. Further implications concern the shaping of morphogen gradients
      along the sinusoidal axis by autophagy, and the different contribution of
      autophagy to the development of various different liver pathologies. The proposed
      dependence of the dual glutamine-dependent regulatory mechanisms of autophagy on
      inverse gradients of Wnt and hedgehog signalling may be relevant for other
      tissues in which GS is heterogeneously expressed.

PMID- 23531206
TI  - 6:2 and 8:2 fluorotelomer alcohol anaerobic biotransformation in digester sludge
      from a WWTP under methanogenic conditions.
AB  - 6:2 FTOH and 8:2 FTOH [FTOHs, F(CF2)nCH2CH2OH, n = 6, 8] are the principal
      polyfluorinated raw materials used to manufacture FTOH-based products, which may
      be released to WWTPs during their product life cycle. For the first time,
      anaerobic biotransformation of FTOHs and key biotransformation intermediates in
      WWTP digester sludge under methanogenic conditions was investigated. 6:2 FTOH was
      transformed to 6:2 FTCA, [F(CF2)6CH2COOH, 32-43 mol %], 6:2 FTUCA
      [F(CF2)5CF?CHCOOH, 1.8-8.0 mol %], and 5:3 acid [F(CF2)5CH2CH2COOH, 18-23 mol %]
      by day 90 and day 176 in two separate studies. 8:2 FTOH was transformed by day
      181 to 8:2 FTCA (18 mol %), 8:2 FTUCA (5.1 mol %), and 7:3 acid (27 mol %). 6:2
      and 8:2 FTOH anaerobic biotransformation led to low levels of perfluorohexanoic
      acid (PFHxA, <=0.4 mol %) and perfluorooctanoic acid (PFOA, 0.3 mol %),
      respectively. 6:2 FTUCA anaerobic biotransformation led to a newly identified
      novel transient intermediate 3-fluoro 5:3 acid [F(CF2)5CFHCH2COOH] and 5:3 acid,
      but not 5:2 sFTOH [F(CF2)5CH(OH)CH3] and alpha-OH 5:3 acid
      [F(CF2)5CH2CH(OH)COOH], two precursors leading to PFPeA (perfluoropentanoic acid)
      and PFHxA. Thus, FTOH anaerobic biotransformation pathways operated by microbes
      in the environment was likely inefficient at shortening carbon chains of FTOHs to
      form PFCAs (perfluorinated carboxylic acids). These results imply that anaerobic
      biotransformation of FTOH-based products may produce polyfluorinated acids, but
      is not likely a major source of PFCAs detected in anaerobic environmental
      matrices such as anaerobic digester sludge, landfill leachate, and anaerobic
      sediment under methanogenic conditions.

PMID- 23531207
TI  - Contrast-noise-ratio (CNR) analysis and optimisation of breast-specific gamma
      imaging (BSGI) acquisition protocols.
AB  - BACKGROUND: Breast cancer is one of the most prevalent forms of cancer in women.
      Breast-specific gamma imaging (BSGI) is a diagnostic imaging method that uses
      sestamibi-labelled 99Tc and a dedicated gamma camera to localize malignant
      lesions in breast tissue. The aim of this study is to investigate if the current
      acquisition protocol for BSGI at our hospital is optimized for the detection of
      lesions in our patients. METHODS: We analyzed patient data and performed a
      phantom study with a Dilon 6800 gamma camera. The patient data were collected
      from a group of 13 patients (740 MBq 99mTc-sestamibi, four views per patient were
      dynamically acquired with a frame duration of 30 s per frame and a total
      acquisition time of 8 min per view). Reduced-time static images were created, and
      contrast-to-noise ratios of identified hotspots were determined for different
      acquisition times. For the phantom study, we used a contrast detail phantom to
      investigate the contrast and resolution properties, within the range of relevant
      clinical acquisition parameters. The phantom was filled with a concentration of
      80 MBq in 500 ml of water, and we dynamically acquired frames for a total
      acquisition time of 60 min using a general purpose (GP) collimator. To compare
      the GP collimator with the high-resolution collimator, a second acquisition was
      made for both collimators with a total acquisition time of 16 min. RESULTS: The
      initial analysis of BSGI scans of the 13 patients showed that a dose reduction by
      a factor of 3 would not have reduced the number of observable hotspots in each of
      the acquired views. However, a subsequent systematic analysis of our protocol
      with a contrast-detail phantom showed that dose reduction results in a lower
      observability of hotspots, whereas increased doses resulted in a higher
      observability. CONCLUSION: We believe that the results of our phantom study are
      relevant for clinical practice and that further dose reduction cannot be
      recommended for the BSGI exams at our hospital and that an increase of the
      administered activity should be considered.

PMID- 23531208
TI  - Blood transfusion in cardiac surgery is a risk factor for increased hospital
      length of stay in adult patients.
AB  - BACKGROUND: Allogeneic red blood cell (RBC) transfusion has been proposed as a
      negative indicator of quality in cardiac surgery. Hospital length of stay (LOS)
      may be a surrogate of poor outcome in transfused patients. METHODS: Data from 502
      patients included in Transfusion Requirements After Cardiac Surgery (TRACS) study
      were analyzed to assess the relationship between RBC transfusion and hospital LOS
      in patients undergoing cardiac surgery and enrolled in the TRACS study. RESULTS:
      According to the status of RBC transfusion, patients were categorized into the
      following three groups: 1) 199 patients (40%) who did not receive RBC, 2) 241
      patients (48%) who received 3 RBC units or fewer (low transfusion requirement
      group), and 3) 62 patients (12%) who received more than 3 RBC units (high
      transfusion requirement group). In a multivariable Cox proportional hazards
      model, the following factors were predictive of a prolonged hospital length of
      stay: age higher than 65 years, EuroSCORE, valvular surgery, combined procedure,
      LVEF lower than 40% and RBC transfusion of > 3 units. CONCLUSION: RBC transfusion
      is an independent risk factor for increased LOS in patients undergoing cardiac
      surgery. This finding highlights the adequacy of a restrictive transfusion
      therapy in patients undergoing cardiac surgery. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: http://NCT01021631.

PMID- 23531209
TI  - Interstitial granulomatous dermatitis with arthritis presenting with the rope
      sign.

PMID- 23531210
TI  - Towards a superior streptokinase for fibrinolytic therapy of vascular thrombosis.
AB  - Medical intervention with fibrinolytic drugs such as tissue plasminogen activator
      (tPA) and streptokinase (SK) is the principal treatment for life-treating
      thromboembolic disorders. Contrary to tPA, SK is a heterogenic and non-human
      (bacterial) protein produced by streptococci and its medical application may
      elicit sever immune and anaphylactic responses that restrict its utilization.
      Besides, human plasminogen (HPG) activation by SK is not blood-clot specific and
      associated with a risk of hemorrhage. Despite these limitations, comparative
      clinical trials on various thrombolytic agents suggested that SK is the most cost
      effective fibrinolytic drug and almost as safe as its other counterparts such as
      tPA. Therefore, a number of studies were conducted to provide structurally
      modified SK with reduced immunogenicity, higher blood-clot specificity and half
      lives. Although there are extensive overlaps in SK structural domains responsible
      for functionality, immunogenicity and stability that may limit its modifications,
      various strategies such as genetic manipulations (amino acid substitution
      /addition /deletion or domain fusions through production of chimeric SK proteins
      linked to HPG or hirudin) and chemical modification such as (homogenous/site
      specific) PEGylation have been employed to develop a superior SK. In addition,
      data of the latest studies on SK screened from different streptococcal sources
      indicated the possibility of retrieving naturally occurring SKs with higher
      activities, less antigenicity and/or more fibrinspecificity. In the present
      review, after a survey on structure function relationships of SK domains and
      different strategies for SK improvement, recent advances and potential
      application of computer and matrix-based analyses for design and introduction of
      superior SKs will be presented. 

PMID- 23531211
TI  - Silver nanoparticle-enhanced fluorescence resonance energy transfer sensor for
      human platelet-derived growth factor-BB detection.
AB  - A silver nanoparticle (AgNP)-enhanced fluorescence resonance energy transfer
      (FRET) sensing system is designed for the sensitive detection of human platelet
      derived growth factor-BB (PDGF-BB). Fluorophore-functionalized aptamers and
      quencher-carrying strands hybridized in duplex are coupled with streptavidin (SA)
      functionalized nanoparticles to form a AgNP-enhanced FRET sensor. The resulting
      sensor shows lower background fluorescence intensity in the duplex state due to
      the FRET effect between fluorophores and quenchers. Upon the addition of PDGF-BB,
      the quencher-carrying strands (BHQ-2) of the duplex are displaced leading to the
      disruption of the FRET effect. As a result, the fluorescent intensity of the
      fluorophore-aptamer within the proximity of the AgNP is increased. When compared
      to the gold nanoparticle (AuNP)-based FRET and bare FRET sensors, the AgNP-based
      FRET sensor showed remarkable increase in fluorescence intensity, target
      specificity, and sensitivity. Results also show versatility of the AgNP in the
      enhancement of sensitivity and selectivity of the FRET sensor. In addition, a
      good linear response was obtained when the PDGF-BB concentrations are in the
      ranges of 100-500 and 6.2-50 ng/mL with the detection limit of 0.8 ng/mL. 

PMID- 23531213
TI  - Murabutide revisited: a review of its pleiotropic biological effects.
AB  - Despite the great efforts put into their development, the list of clinically
      approved immunological adjuvants is still very short. Evolution of the knowledge
      of the immune system has enabled for rational design of novel adjuvants and has
      led to the conclusion that more than one type of adjuvant will be required.
      Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of
      bacterial cell wall peptidoglycan, have gained considerable attention in the past
      decades, because of their potent adjuvant effects. Murabutide is a safe
      derivative of MDP, which interacts with cells of the immune system, both innate
      and adaptive, and exerts its effect through activation of Nod2. The
      transcriptional response of murabutide-stimulated macrophages revealed enhanced
      expression of genes coding for various proteins such as immune mediators and
      their receptors, transcription factors and kinases, ion channels/transporters and
      proteins involved in cell metabolic activity, thus reflecting a broad spectrum of
      biological effects. In addition to its well recognized adjuvant effect,
      murabutide has also been shown to enhance the host's resistance against microbial
      infections, nonspecific resistance against tumors and the induction of cytokines
      and chemokines implicated in enhancing the immune response and hematopoesis. This
      article provides an insight into the mechanism of action of murabutide and its
      interactions with the cells of the immune system in vitro and in vivo. On account
      of its numerous biological effects, murabutide has been the subject of several
      clinical studies. Many of these have confirmed its potential to synergize with
      cytokines of therapeutic interest in potentiating the tumoricidal activity of
      macrophages or targeting chronic viral diseases, as well as reducing the cytokine
      dosage needed to achieve a therapeutic effect. This review covers the findings of
      all relevant studies and focuses on the role of murabutide and its potential in
      the treatment of several microbial diseases.

PMID- 23531212
TI  - Functional characterization of a PEI-CyD-FA-coated adenovirus as delivery vector
      for gene therapy.
AB  - The recombinant adenovirus is evolving as a promising gene delivery vector for
      gene therapy due to its efficiency in transducing different genes into most types
      of cells. However, the host-immune response elicited by primary inoculation of an
      adenovirus can cause rapid clearance of the vector, impairing the efficacy of the
      adenovirus and hence obstructing its clinical application. We have previously
      synthesized a biodegradable co-polymer consisting of a low molecular weight PEI
      (MW 600 Da), cross-linked with beta-cyclodextrin, and conjugated with folic acid
      (PEI-CyD-FA, named H1). Here we report that coating the adenovirus vector (Adv)
      with H1 (H1/rAdv) could significantly improve both the efficacy and biosafety of
      Adv. Enhanced transfection efficiency as well as prolonged duration of gene
      expression were clearly demonstrated either by intratumoral or systemic injection
      of a single dose of H1/rAdv in immunocompetent mice. Importantly, repeated
      injections of H1/rAdv did not reduce the transfection efficiency in
      immunocompetent mice. Furthermore, H1 transformed the surface charge of the
      adenovirus capsomers from negative to positive in physiological solution,
      suggesting that H1 coated the capsid protein of the adenovirus. This could
      shelter the epitopes of capsid proteins of the adenovirus, resulting in a reduced
      host-immune response and enhanced transfection efficiency. Taken together, these
      findings suggest that H1/rAdv is an effective gene delivery system superior to
      the adenovirus alone and that it could be considered as a preferred vehicle for
      gene therapy.

PMID- 23531214
TI  - Antioxidant food supplements and obesity-related inflammation.
AB  - The obesity prevalence is growing worldwide and largely responsible for the
      increased incidence of cardiovascular disease, the most common cause of death in
      the western world. Excessive food intake along with insufficient physical
      exercise is the basic impetus for this development. The obese state is commonly
      associated with an increase in leptin levels and chronic immune-mediated
      inflammation. Despite high leptin levels, the leptin response, normally
      associated with satiety and satiation, seems to be impaired and individuals
      continue to consume calorie-rich food. Antioxidant food additives such as sodium
      sulphite, sodium benzoate and curcumin were shown to suppress the leptin release
      in lipopolysaccharide- treated murine adipocytes. Based on this, we hypothesize
      that the insufficient leptin release, caused by excessive consumption of food
      additives, may lead to a reduced exposure of the central nervous system to leptin
      and ultimately propagate obesity. On the other hand, leptin has been shown to
      favor Th1-type activity, which ultimately decreases tryptophan levels. Tryptophan
      derivatives, serotonin and melatonin, induce satiety/satiation through several
      mechanisms. In this context, the antioxidant suppression of leptin release and
      Th1-type activity is beneficial to increase serotonin and melatonin levels. The
      molecules in the mechanism described in this review are highly integrated in the
      reward system, and have been implicated in the addiction behavior of obesity.
      Based on these facts, the involvement of antioxidant food supplements in the
      mechanisms of the reward-deficiency syndrome which perpetuates obesity will be
      discussed.

PMID- 23531215
TI  - Antineoplastic activities, apoptotic mechanism of action and structural
      properties of a novel silver(I) chelate.
AB  - In a previous work, the author has investigated the antimicrobial and cytotoxic
      properties of tartaric and glutamic acids silver(I) chelates. In a following
      work, the author has reported on the in vitro cytotoxicity and the mechanism of
      action of a silver(I) tartaric acid chelate synthesized by the author given the
      title name Aliargentumycine (AAgM) on hematopoietic malignancies. The in vitro
      antineoplastic activities of AAgM on solid human breast ductal carcinoma (T- 47D)
      and disseminated T-cell acute lymphoblastic leukemia (Jurkat) cell lines, its
      mechanism of action and its structural properties were investigated here. The
      cytotoxicity results of AAgM were compared to cisplatin, a ubiquitously used
      platinum-based antitumor drug. Results have indicated that AAgM demonstrated
      excellent cytotoxicity on both tumor cell lines studied when compared to cis
      platin, especially for T-47D. Unlike cisplatin, AAgM was found to exhibit an
      aberrant triphasic cytotoxicity profile. Phase I exhibited cytotoxicity in the
      nanoconcentration range, Phase II exhibited no cytotoxicity in the intermediate
      range, and finally Phase III exhibited cytotoxicity in the microconcentration
      range. Phase II lacks of cytotoxicity might be an indication of cells reverting
      back to being nonmalignant in a similar way to 5-Aza-2'- deoxycytidine
      (decitabine). Quantitative pharmacokinetic-pharmacodynamic analyses were
      undertaken and were found that AAgM induced significantly better cytotoxic
      activities than cisplatin between 1.9-30.5 ng/mL while cisplatin did not exhibit
      any cytotoxicity on T-47D below 122 ng/mL. TUNEL assay was performed and AAgM was
      found to elicit its antineoplastic activities by apoptosis. X-ray diffraction
      showed that AAgM is a polymeric chain hydrate structure with no imposed symmetry
      and the complex around the silver is a monohydrate distorted skew trapezoidal
      bipyramidal sixcoordinate. AAgM is composed of lipophilic and hydrophilic
      moieties, making AAgM miscible in both lipids via the tartrate rings and ionic
      solutions via the water molecules. The results are expected to have significant
      implications on cancer therapy, especially solid neoplasms, which are
      exceptionally difficult to treat, and those derived from epithelial and
      mesenchymal cells, which are not prone to apoptotic responses with cdk inhibitor
      drugs. Also, the results should be very useful in the design of future novel
      silver-based antineoplastic drugs.

PMID- 23531216
TI  - MEK inhibition increases lapatinib sensitivity via modulation of FOXM1.
AB  - The standard targeted therapy for HER2-overexpressing breast cancer is the HER2
      monoclonal antibody, trastuzumab. Although effective, many patients eventually
      develop trastuzumab resistance. The dual EGFR/HER2 small molecule tyrosine kinase
      inhibitor lapatinib is approved for use in trastuzumab-refractory metastatic HER2
      positive breast cancer. However, lapatinib resistance is a problem as most
      patients with trastuzumab-refractory disease do not benefit from lapatinib.
      Understanding the mechanisms underlying lapatinib resistance may ultimately
      facilitate development of new therapeutic strategies for HER2-overexpressing
      breast cancer. Our current results indicate that MEK inhibition increases
      lapatinib-mediated cytotoxicity in resistant HER2-overexpressing breast cancer
      cells. We genetically and pharmacologically blocked MEK/ERK signaling and
      evaluated lapatinib response by trypan blue exclusion, anchorage-independent
      growth assays, flow cytometric cell cycle and apoptosis analysis, and in tumor
      xenografts. Combined MEK inhibition and lapatinib treatment reduced
      phosphorylated ERK more than single agent treatment. In addition, Western blots,
      immunofluorescence, and immunohistochemistry demonstrated that the combination of
      MEK inhibitor plus lapatinib reduced nuclear expression of the MEK/ERK downstream
      proto-oncogene FOXM1. Genetic knockdown of MEK was tested for the ability to
      increase lapatinib-mediated cell cycle arrest or apoptosis in JIMT-1 and MDA361
      cells. Finally, xenograft studies demonstrated that combined pharmacological
      inhibition of MEK plus lapatinib suppressed tumor growth and reduced expression
      of FOXM1 in HER2-overexpressing breast cancers that are resistant to trastuzumab
      and lapatinib. Our results suggest that FoxM1 contributes to lapatinib resistance
      downstream of MEK signaling, and supports further study of pharmacological MEK
      inhibition to improve response to lapatinib in HER2-overexpressing trastuzumab
      resistant breast cancer.

PMID- 23531217
TI  - Study on medicinal chemistry of K203 in wistar rats and beagle dogs.
AB  - K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase
      reactivator of potential use in organophosphate/ organophosphonate poisoning.
      Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion
      pair HPLC. Serum and cerebrospinal fluid concentrations of K203 were determined
      using ion-pair reversedphase chromatography on octadecyl silica column. HPLC with
      ultraviolet detection was used for determination of serum concentration of K203
      higher than 0.1 MUg/mL while its low concentrations in cerebrospinal fluid
      required electrochemical detection (0.015 through 4 MUg/mL range). In rats the
      serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes
      post administration. Zero order pharmacokinetics was also observed in beagle dogs
      after low dose (15 MUmol/kg) of K203 administration. High dose administration
      (250 MUmol/kg) led to subsequent hindered elimination from both cerebrospinal
      fluid and serum.

PMID- 23531218
TI  - Benzofuran-based estrogen receptor alpha modulators as anti-cancer therapeutics:
      in silico and experimental studies.
AB  - In the search for new estrogen receptor alpha (ERalpha) modulators, a trial
      molecular screening was conducted and 5,6-dihydroxybenzofuran was identified as a
      possible drug target for ERalpha. The target molecular modelling molecule 1 and a
      series of 5,6-dihydroxybenzofurans have been synthesized and evaluated for their
      anti-proliferation activities against MCF-7 and MDA-MB-231 cells. From the SAR
      studies, potential functional groups have been identified, the two hydroxyl
      groups at C-5 and C-6 and the phenyl ring at C-2, which showed considerable
      cytotoxicity in MCF-7 breast cancer cells. In addition, the apoptotic abilities
      of the compounds have been measured in both MCF-7 ER(+) and MDA-MB-231 ER(-)
      breast cancer cells. The results demonstrated that our compounds inhibit MCF-7
      breast cancer cells via ER(+). These preliminary results provide valuable
      information towards the identification of important functional groups present on
      5,6-dihydroxybenzofuran, which could be a promising scaffold for designing novel
      ER ligands.

PMID- 23531219
TI  - Clinical and marketed proteasome inhibitors for cancer treatment.
AB  - The ubiquitin-proteasome pathway (UPP), which influences essential cellular
      functions including cell growth, differentiation, apoptosis, signal transduction,
      antigen processing and inflammatory responses, has been considered as one of the
      most important cellular protein degradation approaches. Proteasome functions as a
      gatekeeper, which controls the execution of protein degradation and plays a
      critical role in the ubiquitin-proteasome pathway. The unfolding of the close
      connection between proteasome and cancer provides a potential strategy for cancer
      treatment by using proteasome inhibitors. Small molecular inhibitors of varied
      structures and potency against proteasome have been discovered in recent years,
      with bortezomib and carfilzomib having been successfully approved for clinical
      application while some other promising candidates are currently under clinical
      trials. Herein, we review the development history of drugs and candidates that
      target the 20S proteasome, structure-activity relationships (SARs) of various
      proteasome inhibitors, and related completed or ongoing clinical trials.

PMID- 23531220
TI  - Protein-ligand docking in the new millennium--a retrospective of 10 years in the
      field.
AB  - Protein-ligand docking is currently an important tool in drug discovery efforts
      and an active area of research that has been the subject of important
      developments over the last decade. These are well portrayed in the rising number
      of available protein-ligand docking software programs, increasing level of
      sophistication of its most recent applications, and growing number of users.
      While starting by summarizing the key concepts in protein-ligand docking, this
      article presents an analysis of the evolution of this important field of research
      over the past decade. Particular attention is given to the massive range of
      alternatives, in terms of protein-ligand docking software programs currently
      available. The emerging trends in this field are the subject of special
      attention, while old established docking alternatives are critically revisited.
      Current challenges in the field of protein-ligand docking such as the treatment
      of protein flexibility, the presence of structural water molecules and its effect
      in docking, and the entropy of binding are dissected and discussed, trying to
      anticipate the next years in the field.

PMID- 23531221
TI  - Insulin secretion and interleukin-1beta dependent mechanisms in human diabetes
      remission after metabolic surgery.
AB  - To compare endocrine, metabolic, and inflammatory changes induced by gastric
      bypass (GB) and sleeve gastrectomy (SG) in patients with type 2 diabetes mellitus
      (T2DM), and to investigate the mechanisms of success after metabolic surgery.
      Sixteen GB and 16 SG patients were followed up before and at 1 year after
      surgery. The 75-g oral glucose tolerance test (OGTT) was performed before and
      after surgery. Glucose homeostasis, serum interleukin-1beta, plasma gut hormones
      and adipokines, and the United Kingdom Prospective Diabetes Study (UKPDS) ten
      year cardiovascular risks were evaluated. The diabetes remission rate was
      significantly higher in GB than SG. Changes in the area under the curve (AUC) for
      glucose were greater in those with complete and partial remission after GB and
      remitters after SG than non-remitters after SG, whereas changes in AUC for C
      peptide were higher in complete and partial remitters after GB than non-remitters
      after SG. Insulinogenic index was enhanced and serum interleukin-1beta was
      reduced in complete remitters after GB and remitters after SG. Logistic
      regression analysis confirmed that insulinogenic index and interleukin-1beta, not
      insulin resistance, were the factors determining the success of diabetes
      remission after metabolic surgeries. GB and SG significantly reduced the ten-year
      risk of coronary heart disease and fatal coronary heart disease in T2DM patients
      after surgery, while GB had the additional benefit of reduced stroke risk. Human
      diabetes remission after metabolic surgery is through insulin secretion and
      interleukin-1beta dependent mechanisms. GB is superior to SG in cardiocerebral
      risk reduction in Asian non-morbidly obese, not well-controlled T2DM patients.

PMID- 23531222
TI  - 1,2,4-Oxadiazoles identified by virtual screening and their non-covalent
      inhibition of the human 20S proteasome.
AB  - Although several constitutive proteasome inhibitors have been reported these
      recent years, potent organic, noncovalent and readily available inhibitors are
      still poorly documented. Here we used a structure- and ligand-based in silico
      approach to identify commercially available 1,2,4-oxadiazole derivatives as non
      covalent human 20S proteasome inhibitors. Their optimization led to the newly
      synthesized compound 4h that is a mixed proteasomal inhibitor of the chymotrypsin
      like activity (K(i) of 26,1 nM and K'(i) of 7.5 nM) which is in addition
      selective versus the challenging cathepsin B and calpain proteases. Molecular
      modelling studies corroborated the mechanism of inhibition and suggest an unusual
      binding of the inhibitor within the S5 binding pocket (beta6 subunit). The
      cellular effects of our compounds validate their utility as potential
      pharmacological agents for anti-cancer pre-clinical studies.

PMID- 23531223
TI  - Applications of natural compounds in the photodynamic therapy of skin cancer.
AB  - Despite significant advances in early diagnosis and treatment, skin cancer is one
      of the leading causes of death. Photodynamic therapy (PDT) is a new therapeutic
      modality that is emerging as an important resource against malignant tumors. This
      strategy is based on the action of photosensitizers, i.e. of molecules which may
      accumulate preferentially inside tumor cells where they exert a cytotoxic effect
      after excitation by light at appropriate wavelengths. Some forms of skin cancers
      and also some non-tumor pathologies are now treated with PDT. Several compounds
      with photosensitizing activity have been identified, and some of these molecules
      are commercially available. Many photoactive principles are natural compounds.
      Numerous reviews in the last decade have focused on photodynamic therapy, its
      effects and applications, but less attention has been paid to plant extracts or
      molecules of natural origin studied for their phototoxic activity to date.This
      review critically examines the potential role of various plant extracts and
      naturally occurring compounds in the treatment of skin cancer. Both in vitro and
      in vivo effects of these agents, together with their known related cellular and
      molecular mechanisms, are presented and discussed. 

PMID- 23531224
TI  - New complexes of chromium(III) containing organic pi-radical ligands: an
      experimental and density functional theory study.
AB  - The electronic structures of a series of chromium complexes 1-7 have been
      experimentally investigated using a combination of X-ray crystallography, magneto
      and electrochemistry, and Cr K-edge X-ray absorption and UV-vis spectroscopies.
      Reaction of the dimer [Cr(II)2(MU-CH3CO2)4](0) with 2,2'-bipyridine (bpy(0))
      produced the complex [Cr(III)(bpy(0))(bpy(*))(CH3CO2)2](0) (S = 1) (1), but in
      the presence of isopropylamine ((i)PrNH2)
      [Cr(III)(bpy(*))((i)PrNH2)2(CH3CO2)2](0) (S = 1) (2) was obtained. Both 1 and 2
      contain a Cr(III) ion and a single (bpy(*))(1-) ligand, so are not low-spin
      Cr(II) species. One-electron oxidation of 1 and 2 yielded
      [Cr(III)(bpy(0))2(CH3CO2)2]PF6 (S = 3/2) (3) in both cases. In addition, the new
      neutral species [Cr(III)(DAD(*))3](0) (S = 0) (4) and [Cr(III)(CF3AP(*))3](0) (S
      = 0) (5) have been synthesized. Both complexes contain three pi-radical anion
      ligands, which derive from one electron reduction of 1,4-bis(cyclohexyl)-1,4
      diaza-1,3-butadiene and one electron oxidation of 2-(2-trifluoromethyl)-anilino
      4,6-di-tert-butylphenolate, respectively. Intramolecular antiferromagnetic
      coupling to d(3) Cr(III) gives the observed singlet ground states. Reaction of
      [Cr(II)(CH3CN)6](PF6)2 with 2,6-bis[1-(4-methoxyphenylimino)ethyl]pyridine
      (PDI(0)) under anaerobic conditions affords dark brown microcrystals of
      [Cr(III)(PDI(0))(PDI(*))](PF6)2 (S = 1) (6). This complex is shown to be a member
      of the electron transfer series [Cr(III)(PDI)2](3+/2+/1+/0), in which all one
      electron transfer processes are ligand-based. By X-ray crystallography, it was
      shown that 6 possesses a localized electronic structure, such that one ligand is
      neutral (PDI(0)) and the other is a pi-radical monoanion (PDI(*))(1-). Again, it
      should be highlighted that 6 is not a Cr(II) species. Lastly, the structure of
      [Cr(III)((Me)bpy(*))3](0) (S = 0) (7, (Me)bpy = 4,4'-dimethyl-2,2'-bipyridine)
      has been established by high resolution X-ray crystallography and clearly shows
      that three ((Me)bpy(*))(1-) radical anions are present. To further validate our
      electronic structure assignments, complexes 1-6 were investigated computationally
      using density functional theory (DFT) and found in all cases to contain a Cr(III)
      ion. This oxidation state assignment was experimentally confirmed for complexes
      2, 4, 5, and 6 by Cr K-edge X-ray absorption spectroscopy.

PMID- 23531225
TI  - Morphology and adhesion strength of myoblast cells on photocurable gelatin under
      native and non-native micromechanical environments.
AB  - We have quantitatively determined how the morphology and adhesion strength of
      myoblast cells can be regulated by photocurable gelatin gels, whose mechanical
      properties can be fine-tuned by a factor of 10(3) (0.1 kPa <= E <= 140 kPa). The
      use of such gels allows for the investigation of mechanosensing of cells not only
      near the natural mechanical microenvironments (E ~ 10 kPa) but also far below and
      beyond of the natural condition. Optical microscopy and statistical image
      analysis revealed that myoblast cells sensitively adopt their morphology in
      response to the substrate elasticity at E ~ 1-20 kPa, which can be characterized
      by the significant changes in the contact area and order parameters of actin
      cytoskeletons. In contrast, the cells in contact with the gels with lower elastic
      moduli remained almost round, and the increase in the elasticity beyond E ~ 20
      kPa caused no distinct change in morphology. In addition to the morphological
      analysis, the adhesion strength was quantitatively evaluated by measuring the
      critical detachment pressure with an aid of intensive pressure waves induced by
      picosecond laser pulses. This noninvasive technique utilizing extremely short
      pressure waves (pulse time width ~100 ns) enables one to determine the critical
      pressure for cell detachment with reliable statistics while minimizing the
      artifacts arising from the inelastic deformation of cells. The adhesion strength
      also exhibited a transition from weak adhesion to strong adhesion within the same
      elasticity range (E ~ 1-20 kPa). A clear correlation between the cell morphology
      and adhesion strength suggests the coupling of the strain of the substrate and
      the mechanosensors near focal adhesion sites.

PMID- 23531226
TI  - Exercise training in childhood-onset systemic lupus erythematosus: a controlled
      randomized trial.
AB  - INTRODUCTION: Exercise training has emerged as a promising therapeutic strategy
      to counteract physical dysfunction in adult systemic lupus erythematosus.
      However, no longitudinal studies have evaluated the effects of an exercise
      training program in childhood-onset systemic lupus erythematosus (C-SLE)
      patients. The objective was to evaluate the safety and the efficacy of a
      supervised aerobic training program in improving the cardiorespiratory capacity
      in C-SLE patients. METHODS: Nineteen physically inactive C-SLE patients were
      randomly assigned into two groups: trained (TR, n = 10, supervised moderate
      intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body
      mass index (BMI)- and age-matched healthy children were recruited as controls (C,
      n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE
      and after 12 weeks of training (POST). Main measurements included exercise
      tolerance and cardiorespiratory measurements in response to a maximal exercise
      (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery
      (DeltaHRR) (that is, the difference between HR at peak exercise and at both the
      first (DeltaHRR1) and second (DeltaHRR2) minutes of recovery after exercise).
      RESULTS: The C-SLE NT patients did not present changes in any of the
      cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise
      training program was effective in promoting significant increases in time-to
      exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P =
      0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in DeltaHRR1 and DeltaHRR2 (P =
      0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when
      compared with the NT group. Moreover, cardiorespiratory parameters were
      comparable between C-SLE TR patients and C subjects after the exercise training
      intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K
      scores remained stable throughout the study. CONCLUSION: A 3-month aerobic
      exercise training was safe and capable of ameliorating the cardiorespiratory
      capacity and the autonomic function in C-SLE patients. TRIAL REGISTRATION:
      NCT01515163.

PMID- 23531227
TI  - When the face fits: recognition of celebrities from matching and mismatching
      faces and voices.
AB  - The results of two experiments are presented in which participants engaged in a
      face-recognition or a voice-recognition task. The stimuli were face-voice pairs
      in which the face and voice were co-presented and were either "matched" (same
      person), "related" (two highly associated people), or "mismatched" (two unrelated
      people). Analysis in both experiments confirmed that accuracy and confidence in
      face recognition was consistently high regardless of the identity of the
      accompanying voice. However accuracy of voice recognition was increasingly
      affected as the relationship between voice and accompanying face declined.
      Moreover, when considering self-reported confidence in voice recognition,
      confidence remained high for correct responses despite the proportion of these
      responses declining across conditions. These results converged with existing
      evidence indicating the vulnerability of voice recognition as a relatively weak
      signaller of identity, and results are discussed in the context of a person
      recognition framework. 

PMID- 23531228
TI  - Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney,
      heart and brain.
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by
      alpha-galactosidase A deficiency leading to renal, cardiac, cerebrovascular
      disease and premature death. Treatment with alpha-galactosidase A (enzyme
      replacement therapy, ERT) stabilises disease in some patients, but long term
      effectiveness is unclear. METHODS: Renal, cardiac, and cerebral outcomes were
      prospectively studied in males and females with Fabry disease treated with ERT.
      Additionally, the occurrence of major cardiac events, stroke, end-stage renal
      disease and death was compared to a natural history (NH) cohort meeting treatment
      criteria. RESULTS: Of 75 patients on ERT (median treatment duration 5.2 years,
      range 0.05-11.0), prospective follow-up was available for 57 adult patients (30
      males) and 6 adolescents. Renal function declined in males (-3.4 ml/min/1.73 m2
      per year, SE 0.2; p < 0.001) despite ERT, but followed the normal course in
      females (-0.8 ml/min/1.73 m2 per year, SE 0.3; p = 0.001). Cardiac mass increased
      during ERT in males (+ 1.2 gram/m2.7, SE 0.3; p < 0.001), but remained stable in
      females (-0.3 gram/m2.7 per year, SE 0.4; p = 0.52). ERT did not prevent the
      occurrence of cerebral white matter lesions. Comparison of ERT treated to
      untreated patients revealed that the odds to develop a first complication
      increased with age (OR 1.05 (95% CI: 1.0-1.1) per year, p = 0.012). For
      development of a first or second complication the odds declined with longer
      treatment duration (OR 0.81 (95% CI: 0.68-0.96) per year of ERT, p = 0.015;OR
      0.52 (0.31-0.88), p = 0.014 respectively). CONCLUSIONS: Long term ERT does not
      prevent disease progression, but the risk of developing a first or second
      complication declines with increasing treatment duration. ERT in advanced Fabry
      disease seems of doubtful benefit.

PMID- 23531229
TI  - Synovial distribution of "systemically" administered acetylsalicylic acid in the
      isolated perfused equine distal limb.
AB  - BACKGROUND: This study investigated synovial concentrations of acetylsalicylic
      acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint
      following systemic administration of ASA. Salicylates were chosen because SA is
      the only nonsteroidal anti-inflammatory drug for which threshold levels exist for
      plasma and urine in equine sports. To avoid animal experiments, the study was
      conducted using an ex vivo model of the isolated perfused equine distal limb in
      combination with plasma concentrations obtained from literature.Salicylate
      concentrations in the joint were determined using microdialysis and high
      performance liquid chromatography (HPLC). Any anti-inflammatory effect of
      synovial ASA concentrations was assessed using an ASA EC50 (half maximal
      effective concentration) determined in equine whole blood. RESULTS: The ASA
      concentration in the synovial fluid (n=6) reached a maximum of 4 MUg/mL, the mean
      concentration over the entire perfusion period was 2 MUg/mL. Maximum SA
      concentration was 17 MUg/mL, the average was 14 MUg/mL. ASA and SA concentration
      in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after
      "systemic" administration, respectively. CONCLUSIONS: ASA and SA accumulated in
      the in the synovial fluid of the ex vivo model despite decreasing systemic
      concentrations. This suggests a prolonged anti-inflammatory effect within the
      joint that remains to be further elucidated.

PMID- 23531230
TI  - Reporting of analyses from randomized controlled trials with multiple arms: a
      systematic review.
AB  - BACKGROUND: Multiple-arm randomized trials can be more complex in their design,
      data analysis, and result reporting than two-arm trials. We conducted a
      systematic review to assess the reporting of analyses in reports of randomized
      controlled trials (RCTs) with multiple arms. METHODS: The literature in the
      MEDLINE database was searched for reports of RCTs with multiple arms published in
      2009 in the core clinical journals. Two reviewers extracted data using a
      standardized extraction form. RESULTS: In total, 298 reports were identified.
      Descriptions of the baseline characteristics and outcomes per group were missing
      in 45 reports (15.1%) and 48 reports (16.1%), respectively. More than half of the
      articles (n = 171, 57.4%) reported that a planned global test comparison was used
      (that is, assessment of the global differences between all groups), but 67
      (39.2%) of these 171 articles did not report details of the planned analysis. Of
      the 116 articles reporting a global comparison test, 12 (10.3%) did not report
      the analysis as planned. In all, 60% of publications (n = 180) described planned
      pairwise test comparisons (that is, assessment of the difference between two
      groups), but 20 of these 180 articles (11.1%) did not report the pairwise test
      comparisons. Of the 204 articles reporting pairwise test comparisons, the
      comparisons were not planned for 44 (21.6%) of them. Less than half the reports
      (n = 137; 46%) provided baseline and outcome data per arm and reported the
      analysis as planned. CONCLUSIONS: Our findings highlight discrepancies between
      the planning and reporting of analyses in reports of multiple-arm trials.

PMID- 23531231
TI  - Integration of mechanotransduction concepts in bone tissue engineering.
AB  - Mechanical stimulus has been identified for a long time as a key player in the
      adaptation of the musculo-skeletal tissues to their function. Mechanical loading
      is then an intrinsic variable to be considered when new developments are proposed
      in bone tissue engineering. By combining structural biomechanics and
      mechanotransduction aspects, a new paradigm is presented for bone tissue
      engineering. It is proposed that in vivo mechanical loading be used to increased
      bone formation in the scaffold instead of pre-seeding the scaffold with cells or
      delivering growth factors. In this article, we demonstrated the feasibility of
      this approach and compared it to the classical tissue engineering strategy. In
      particular, we showed that bone formation could be increased in the scaffold that
      underwent mechanical loading during an in vivo study in rats. A model of bone
      formation was then proposed to translate the in vivo results into a possible
      clinical application where the loading of the scaffold would be transmitted by
      the sharing of the load between an implant and the bone scaffold. 

PMID- 23531233
TI  - Two-dimensional charge-separated metal-organic framework for hysteretic and
      modulated sorption.
AB  - A charge-separated metal-organic framework (MOF) has been successfully
      synthesized from an imidazolium tricarboxylate ligand, N-(3,5-dicarboxylphenyl)
      N'-(4-carboxylbenzyl)imidazolium chloride (DCPCBImH3Cl), and a zinc(II) dimeric
      secondary building unit, namely, DCPCBim-MOF-Zn, which shows an unprecedented 3,6
      connected two-dimensional net topology with the point (Schlafli) symbol
      (4(2).6)2(4(4).6(9).8(2)). The framework contains one-dimensional highly polar
      channels, and density functional theory calculations show that positive charges
      are located on the imidazolium/phenyl rings and negative charges on the
      carboxylate moieties. The charge-separated nature of the pore surface has a
      profound effect in their adsorption behavior, resulting in remarkable hysteretic
      sorption of various gases and vapors. For CO2, the hysteretic sorption was
      observed to occur even up to 298 K. Additionally, trace chloride anions present
      in the pore channels are able to modulate the gas-sorption behavior.

PMID- 23531232
TI  - Clustering of diet- and activity-related parenting practices: cross-sectional
      findings of the INPACT study.
AB  - BACKGROUND: Various diet- and activity-related parenting practices are positive
      determinants of child dietary and activity behaviour, including home
      availability, parental modelling and parental policies. There is evidence that
      parenting practices cluster within the dietary domain and within the activity
      domain. This study explores whether diet- and activity-related parenting
      practices cluster across the dietary and activity domain. Also examined is
      whether the clusters are related to child and parental background
      characteristics. Finally, to indicate the relevance of the clusters in
      influencing child dietary and activity behaviour, we examined whether clusters of
      parenting practices are related to these behaviours. METHODS: Data were used from
      1480 parent-child dyads participating in the Dutch IVO Nutrition and Physical
      Activity Child cohorT (INPACT). Parents of children aged 8-11 years completed
      questionnaires at home assessing their diet- and activity-related parenting
      practices, child and parental background characteristics, and child dietary and
      activity behaviours. Principal component analysis (PCA) was used to identify
      clusters of parenting practices. Backward regression analysis was used to examine
      the relationship between child and parental background characteristics with
      cluster scores, and partial correlations to examine associations between cluster
      scores and child dietary and activity behaviours. RESULTS: PCA revealed five
      clusters of parenting practices: 1) high visibility and accessibility of screens
      and unhealthy food, 2) diet- and activity-related rules, 3) low availability of
      unhealthy food, 4) diet- and activity-related positive modelling, and 5) positive
      modelling on sports and fruit. Low parental education was associated with
      unhealthy cluster 1, while high(er) education was associated with healthy
      clusters 2, 3 and 5. Separate clusters were related to both child dietary and
      activity behaviour in the hypothesized directions: healthy clusters were
      positively related to obesity-reducing behaviours and negatively to obesity
      inducing behaviours. CONCLUSION: Parenting practices cluster across the dietary
      and activity domain. Parental education can be seen as an indicator of a broader
      parental context in which clusters of parenting practices operate. Separate
      clusters are related to both child dietary and activity behaviour. Interventions
      that focus on clusters of parenting practices to assist parents (especially low
      educated parents) in changing their child's dietary and activity behaviour seems
      justified.

PMID- 23531235
TI  - In situ nanoplasmonic probing of enzymatic activity of monolayer-confined glucose
      oxidase on colloidal nanoparticles.
AB  - In situ probing protein-particle interactions and activities of proteins on
      colloidal nanoparticle (NP) surfaces is a long-standing key challenge in
      understanding the nanobio interfaces and virtually important for a variety of
      biological and biomedical applications. The interactions of NPs with proteins,
      for instance, are known to form NP bioconjugates or protein coronas; protein
      surface immobilization and molecular layer-by-layer deposition techniques are
      widely used, but a clear understanding of the confinement effect on protein
      activity by molecular coating, at the monolayer level, remains poorly understood.
      We explore here a novel approach, using colloidal plasmonic nanocomplexes coated
      with glucose oxidase (GOx) as self-sensing nanoprobes for in situ optical probing
      of surface-confined enzymatic activity, which is at least 1-2 orders of magnitude
      more sensitive than standard colorimetric assays for detecting GOx activity. We
      found that enzymatic activity of monolayer-confined GOx on colloidal NPs was
      significantly enhanced as compared with free GOx (also proved by conformational
      changes from circular dichroism studies), with a low apparent Michaelis-Menten
      constant Km of ~0.115 mM and high turnover kcat/Km of ~8394 M(-1).s(-1); compared
      with the "anchored-type" suspending GOx, the outmost polyelectrolyte monolayer
      protected "sandwiched-type" GOx exhibits significantly improved enzymatic
      activities toward higher temperatures and wider pH range. This finding is of
      fundamental important and instructive for safe use of such nanomaterials for
      bioapplications.

PMID- 23531236
TI  - Abstracts of the Urological Society of Australia and New Zealand 66th Annual
      Scientific Meeting. Melbourne, Australia. April 13-16, 2013.

PMID- 23531234
TI  - Experimental designs for small randomised clinical trials: an algorithm for
      choice.
AB  - BACKGROUND: Small clinical trials are necessary when there are difficulties in
      recruiting enough patients for conventional frequentist statistical analyses to
      provide an appropriate answer. These trials are often necessary for the study of
      rare diseases as well as specific study populations e.g. children. It has been
      estimated that there are between 6,000 and 8,000 rare diseases that cover a broad
      range of diseases and patients. In the European Union these diseases affect up to
      30 million people, with about 50% of those affected being children. Therapies for
      treating these rare diseases need their efficacy and safety evaluated but due to
      the small number of potential trial participants, a standard randomised
      controlled trial is often not feasible. There are a number of alternative trial
      designs to the usual parallel group design, each of which offers specific
      advantages, but they also have specific limitations. Thus the choice of the most
      appropriate design is not simple. METHODS: PubMed was searched to identify
      publications about the characteristics of different trial designs that can be
      used in randomised, comparative small clinical trials. In addition, the contents
      tables from 11 journals were hand-searched. An algorithm was developed using
      decision nodes based on the characteristics of the identified trial designs.
      RESULTS: We identified 75 publications that reported the characteristics of 12
      randomised, comparative trial designs that can be used in for the evaluation of
      therapies in orphan diseases. The main characteristics and the advantages and
      limitations of these designs were summarised and used to develop an algorithm
      that may be used to help select an appropriate design for a given clinical
      situation. We used examples from publications of given disease-treatment-outcome
      situations, in which the investigators had used a particular trial design, to
      illustrate the use of the algorithm for the identification of possible
      alternative designs. CONCLUSIONS: The algorithm that we propose could be a useful
      tool for the choice of an appropriate trial design in the development of orphan
      drugs for a given disease-treatment-outcome situation.

PMID- 23531237
TI  - Germline deletion of beta2 microglobulin or CD1d reduces anti-phospholipid
      antibody, but increases autoantibodies against non-phospholipid antigens in the
      NZB/W F1 model of lupus.
AB  - INTRODUCTION: beta2-microglobulin (beta2m) is required for the surface expression
      of MHC class I and class I-like proteins such as CD1d, Qa1 and neonatal Fc
      receptor (FcRn), all of which may impact the development of autoimmunity. Since
      CD1d is known to bind and present phospholipid antigens to T cells, we asked if
      the deficiency of beta2m or CD1d will impact the development of anti-phospholipid
      antibodies as compared to other aspects of lupus autoimmunity. METHODS: We
      introgressed the beta2m-null genotype onto the NZB and NZW backgrounds for 12 to
      14 generations to generate genetically lupus-susceptible (NZB/NZW)F1 (BWF1) mice
      that are beta2m-deficient (beta2m degrees ). Circulating immunoglobulins (Ig),
      rheumatoid factor (RF), anti-DNA and anti-cardiolipin (anti-CL) antibodies, and
      renal disease were analyzed in these and CD1d-deficient (CD1d degrees ) BWF1 mice
      that we had previously generated. RESULTS: Whereas beta2m degrees  BWF1 mice had
      reduced serum IgG, they had increased mortality, nephritis, serum IgG anti-DNA
      antibody and RF as compared to heterozygous and wild-type littermates. These
      effects were recapitulated in CD1d degrees  BWF1 mice, except that they also had
      increased serum IgG as compared to control littermates. Intriguingly, both beta2m
      degrees  and CD1d degrees  mice had lower serum anti-CL antibody levels than in
      control littermates. Such CD1d dependence of anti-CL antibody production is not
      mediated by CD1d/glycolipid-reactive iNKT cells, as these cells reduced the
      production of RF and anti-DNA antibodies but had no effect on anti-CL antibodies.
      CONCLUSIONS: We report a novel dichotomous role of beta2m and CD1d, whereby these
      molecules differently regulate autoimmunity against phospholipid versus non
      phospholipid autoantigens.

PMID- 23531238
TI  - An ELISA for the quantitation of von Willebrand factor: osteoprotegerin complexes
      in plasma.
AB  - BACKGROUND: Von Willebrand factor (VWF) is pivotal in arterial thrombosis, and
      osteoprotegerin (OPG) is besides being a bone protein also related to
      cardiovascular diseases. OPG can bind VWF, but the significance of this
      interaction is not known. OBJECTIVES: The aim was to develop an assay for
      measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human
      plasma. Furthermore, the significance of VWF:OPG complex as a marker of
      cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA
      for quantification of VWF:OPG was developed using a polyclonal rabbit anti-human
      VWF capturing antibody and a monoclonal anti-human OPG detecting antibody.
      Samples were quantified relative to a standard curve obtained from dilutions of a
      plasma pool from healthy individuals. The assay was evaluated in two groups of
      patients with CVD and two groups of asymptomatic individuals with and without
      documented coronary calcification (total n=118). RESULTS AND CONCLUSIONS: The
      assay detected VWF:OPG complexes in human plasma, while no significant signal was
      observed when testing solutions containing VWF or recombinant OPG alone.
      Importantly, the ELISA assay was able to detect in vitro formed complexes between
      human VWF and recombinant OPG in a dose-dependent manner. There was a large inter
      individual variation in plasma VWF:OPG levels, but we found no significant
      differences in the level of VWF:OPG complexes between the four groups. Thus, we
      conclude that increasing OPG plasma levels in atherosclerotic CVD are not derived
      from increased levels of complexed form of VWF and OPG, but are more likely due
      to increased amounts of OPG secreted into the circulation.

PMID- 23531239
TI  - Magnetic resonance imaging and genetic investigation of a case of Rottweiler
      leukoencephalomyelopathy.
AB  - BACKGROUND: Leukoencephalomyelopathy is an inherited neurodegenerative disorder
      that affects the white matter of the spinal cord and brain and is known to occur
      in the Rottweiler breed. Due to the lack of a genetic test for this disorder,
      post mortem neuropathological examinations are required to confirm the diagnosis.
      Leukoencephalopathy with brain stem and spinal cord involvement and elevated
      lactate levels is a rare, autosomal recessive disorder in humans that was
      recently described to have clinical features and magnetic resonance imaging (MRI)
      findings that are similar to the histopathologic lesions that define
      leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and
      spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a
      mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to
      present the results of MRI and candidate gene analysis of a case of Rottweiler
      leukoencephalomyelopathy to investigate the hypothesis that
      leukoencephalomyelopathy in Rottweilers could serve as an animal model of human
      leukoencephalopathy with brain stem and spinal cord involvement. CASE
      PRESENTATION: A two-and-a-half-year-old male purebred Rottweiler was evaluated
      for generalised progressive ataxia with hypermetria that was most evident in the
      thoracic limbs. MRI (T2-weighted) demonstrated well-circumscribed hyperintense
      signals within both lateral funiculi that extended from the level of the first to
      the sixth cervical vertebral body. A neurodegenerative disorder was suspected
      based on the progressive clinical course and MRI findings, and Rottweiler
      leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2
      gene was investigated as a causative candidate, but a sequence analysis failed to
      identify any disease-associated variants in the DNA sequence. CONCLUSION: It was
      concluded that MRI may aid in the pre-mortem diagnosis of suspected cases of
      leukoencephalomyelopathy. Genes other than DARS2 may be involved in Rottweiler
      leukoencephalomyelopathy and may also be relevant in human leukoencephalopathy
      with brain stem and spinal cord involvement.

PMID- 23531241
TI  - [Striving for promotion of standavization and humanity of practical medicine].

PMID- 23531242
TI  - [Controversies in the management of endometriosis and infertility].

PMID- 23531240
TI  - Plantar flexion force induced by amplitude-modulated tendon vibration and
      associated soleus V/F-waves as an evidence of a centrally-mediated mechanism
      contributing to extra torque generation in humans.
AB  - BACKGROUND: High-frequency trains of electrical stimulation applied over the
      human muscles can generate forces higher than would be expected by direct
      activation of motor axons, as evidenced by an unexpected relation between the
      stimuli and the evoked contractions, originating what has been called "extra
      forces". This phenomenon has been thought to reflect nonlinear input/output
      neural properties such as plateau potential activation in motoneurons. However,
      more recent evidence has indicated that extra forces generated during electrical
      stimulation are mediated primarily, if not exclusively, by an intrinsic muscle
      property, and not from a central mechanism as previously thought. Given the
      inherent differences between electrical and vibratory stimuli, this study aimed
      to investigate: (a) whether the generation of vibration-induced muscle forces
      results in an unexpected relation between the stimuli and the evoked contractions
      (i.e. extra forces generation) and (b) whether these extra forces are accompanied
      by signs of a centrally-mediated mechanism or whether intrinsic muscle properties
      are the predominant mechanisms. METHODS: Six subjects had their Achilles tendon
      stimulated by 100 Hz vibratory stimuli that linearly increased in amplitude (with
      a peak-to-peak displacement varying from 0 to 5 mm) for 10 seconds and then
      linearly decreased to zero for the next 10 seconds. As a measure of motoneuron
      excitability taken at different times during the vibratory stimulation, short
      latency compound muscle action potentials (V/F-waves) were recorded in the soleus
      muscle in response to supramaximal nerve stimulation. RESULTS: Plantar flexion
      torque and soleus V/F-wave amplitudes were increased in the second half of the
      stimulation in comparison with the first half. CONCLUSION: The present findings
      provide evidence that vibratory stimuli may trigger a centrally-mediated
      mechanism that contributes to the generation of extra torques. The vibration
      induced increased motoneuron excitability (leading to increased torque
      generation) presumably activates spinal motoneurons following the size principle,
      which is a desirable feature for stimulation paradigms involved in rehabilitation
      programs and exercise training.

PMID- 23531243
TI  - [Study on the factors associated with clinical pregnancy rate of in-vitro
      fertilization in endometriosis related infertility].
AB  - OBJECTIVE: To evaluate the factors associated with clinical pregnancy rate of in
      vitro fertilization (IVF) in endometriosis related infertility. METHODS: Total of
      326 patients with endometriosis related infertility undergoing IVF between
      January 2007 and December 2011 were studied in Department of Reproductive
      Medicine, First Affiliated Hospital, Nanjing Medical University, retrospectively,
      which were divided into 141 cases in clinical pregnancy group and 185 cases in
      non-pregnancy group. Those factors including age, body mass index (BMI), basic
      FSH, antral follicle count (AFC), CA125 and CA199, endometriotic stage and
      history of surgery, stimulation scheme were analyzed by bivariate analysis and
      multivariable logistic regression. RESULTS: (1) Pregnancy rate:total of 141
      pregnant cases and 185 non-pregnant cases treated by IVF were observed, pregnancy
      rate was 43.2% (141/326). (2) Basic parameters: there was no statistical
      difference in age, BMI, basic FSH, AFC, CA125 and CA199 between clinical
      pregnancy group and non-pregnancy group (P > 0.05). (3) Bivariate analysis:
      clinical pregnancy rate of 50.0% (87/174) among patients with infertility year
      less than five years was significantly higher than 35.5% (54/152) in patients
      with more than five years. Pregnancy rate of 56.1% (46/82) in stage I-II was
      significantly higher than 42.5% (79/186) in stage III-IV. Pregnancy rate of 46.6%
      (125/268) with history of surgery was significantly higher than 27.6% (16/58)
      with no history of surgery (P < 0.05). Pregnancy rate of 48.2% (79/164) in long
      term scheme was higher than 38.3% (62/162) in short-term scheme, but there was no
      significant difference (P = 0.075). (4) Multivariable logistic regression:
      clinical pregnancy rate of infertility year with less than 5 years, stage I-II,
      history of surgery proved stage I-II and stage III-IV was significantly higher
      compared with infertility year more than 5 years, stage III-IV and no history of
      surgery respectively (adjusted OR and 95%CI: 2.003, 1.263 - 3.175; 1.899, 1.110 -
      3.248; 3.769, 1.802 - 7.887, P < 0.05). CONCLUSION: Factors affecting clinical
      pregnancy rate of IVF in endometriosis related infertility were infertility year,
      stage and surgery.

PMID- 23531244
TI  - [Impact on ovarian reserve function by different homostasis methods during
      laparoscopic cystectomy in treatment of ovarian endometrioma].
AB  - OBJECTIVE: To investigate the impact on ovarian reserve function by different
      hemostasis methods during laparoscopic surgery in treatment of ovarian
      endometrioma. METHODS: From September 2008 to February 2010, 162 cases with
      ovarian endometrioma undergoing laparoscopic surgery in Shandong Provincial
      Hospital were enrolled in this study. At the 3rd day of the menstrual cycle
      before surgery and the 1st, 3rd, 6th and 12th cycle after surgery, serum FSH and
      anti-mullerian hormone (AMH) and ultrasound basal antral follicle count (AFC) and
      peak systolic velocity (PSV) were examined and compared. Based on hemostasis
      method, those patients were divided into 3 groups, including 54 cases in bipolar
      hemostasis, 54 cases in ultrasonic scalpel hemostasis and suture after excision
      of endometrioma. RESULTS: (1) Before surgery: no significant different factors
      among three groups before surgery were observed, including age, size of
      endometrioma, the level of FSH, AMH, AFC, PSV(P > 0.05). (2) Ovarian reserve
      function after surgery: 1) FSH: at the 1st, 3rd, 6th and 12th month follow-up,
      the FSH in the bipolar group was (11.7 +/- 4.0), (9.9 +/- 4.0), (9.5 +/- 4.3),
      (9.5 +/- 3.9) U/L, and the FSH in ultrasonic scalpel group was (11.4 +/- 4.3),
      (9.7 +/- 4.0), (9.2 +/- 3.7), (9.9 +/- 4.6) U/L, were significantly higher than
      (9.3 +/- 3.8), (6.7 +/- 3.0), (6.5 +/- 3.2), (6.4 +/- 2.2) U/L in suture group
      respectively (all P < 0.05). 2) AMH: at the 1st, 3rd, 6th and 12th month follow
      up, the AMH in the bipolar group was (1.8 +/- 0.9), (1.8 +/- 1.0), (1.9 +/- 1.0),
      (2.0 +/- 1.0) ug/L, and the AMH in the ultrasonic scalpel group was (1.6 +/-
      0.8), (1.8 +/- 1.0), (2.0 +/- 1.1), (2.1 +/- 1.0) ug/L, which were significantly
      lower than (2.8 +/- 1.7), (2.9 +/- 1.6), (3.0 +/- 1.3), (3.2 +/- 1.5) ug/L in
      suture group, respectively (all P < 0.05). 3) AFC: there was no significant
      difference of APC among the three groups in the 1st month after surgery. However,
      at the 3rd, 6th and 12th month follow-up, the AFC of 4.8 +/- 1.4, 5.9 +/- 1.5,
      6.1 +/- 1.5 in the suture group was significant higher than 3.7 +/- 1.4, 4.1 +/-
      1.4, 4.0 +/- 1.5 in bipolar group and 3.6 +/- 1.3, 4.0 +/- 1.1, 3.9 +/- 1.5 in
      ultrasonic group, respectively (all P < 0.05). 4) PSV: at the 1st, 3rd, 6th and
      12th month follow-up, the PSV of the bipolar group (7.9 +/- 3.5), (8.1 +/- 3.3),
      (8.4 +/- 3.1), (8.6 +/- 3.0) cm/s in bipolar group and (8.1 +/- 3.5), (8.0 +/-
      3.0), (7.9 +/- 3.2), (8.0 +/- 2.9) cm/s in ultrasonic group were significant
      lower than (10.9 +/- 3.3), (12.0 +/- 3.2), (11.8 +/- 3.0), (12.1 +/- 4.1) cm/s in
      suture group, respectively. (all P < 0.05). CONCLUSIONS: Bipolar or ultrasonic
      scalpel hemostasis during laparoscopic excision of ovarian endometrioma is
      associated with a significant reduction in ovarian reserve. Electrocoagulation of
      the ovarian tissue should be avoided.

PMID- 23531246
TI  - [Analysis of clinical characteristics and perinatal outcome of early-onset
      intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To analyze the clinical characteristics and perinatal outcome of early
      onset intrahepatic cholestasis of pregnancy (ICP). METHODS: A total of 305 ICP
      cases were collected in the First Affiliated Hospital of Chongqing Medical
      University between June 2006 and May 2012. According to the onset time of ICP,
      patients were divided into early-onset ICP group (onset time < 28 gestational
      weeks) and late-onset ICP group (onset time >= 28 gestational weeks). The late
      onset ICP group was further divided into 28 - 31(+6) gestational weeks and >= 32
      gestational weeks according to the onset time. The biochemical indices and
      perinatal outcome of each group were assessed. RESULTS: (1) When the diagnosis
      was made for the first time, the maternal serum concentrations of total bile acid
      (TBA) and total bilirubin (TBIL) in early-onset ICP group were (41 +/- 9) and (32
      +/- 9) umol/L, respectively; while TBA and TBIL in late-onset ICP group were (32
      +/- 6) and (22 +/- 9) umol/L, and the difference between the two groups was
      statistically significant (P < 0.05). (2) There was no significant difference in
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between early
      onset ICP group and late-onset ICP group (P > 0.05). The ALT of early-onset ICP
      group and late-onset ICP group were (159 +/- 50) and (145 +/- 52) U/L,
      respectively; and AST were (151 +/- 49) and (138 +/- 44) U/L, respectively. (3)
      The early-onset ICP group had significant higher (P < 0.05) incidence of meconium
      staining (18.8% vs. 7.4%), fetal distress (22.9% vs. 8.9%), newborn asphyxia
      (14.6% vs. 5.4%), premature delivery (33.3% vs. 15.6%), developing into severe
      ICP (41.7% vs. 25.3%) and cesarean section (91.7% vs. 78.6%) when compared to the
      late-onset ICP group. No significant difference in the incidence of premature
      delivery, developing into severe ICP and cesarean section was found between the
      two types of late-onset ICP. (4) There was significant differences in average
      birth weight and gestational weeks at delivery between the two groups [early
      onset ICP group: (3113 +/- 443) g and (36.3 +/- 2.6) weeks]; late-onset ICP
      group: [(3513 +/- 450) g and (37.7 +/- 1.6) weeks]. CONCLUSION: The early-onset
      ICP patients presented worse clinical manifestations than late-onset ICP
      patients, and early-onset ICP is more likely to lead to premature delivery and
      fetal distress.

PMID- 23531245
TI  - [Clinical effect on women with different types of endometriosis related
      infertility treated by conservative surgery].
AB  - OBJECTIVE: To study pregnancy outcome and recurrence in patients with different
      type of endometriosis related infertility treated by conservative surgery.
      METHODS: From January 2005 to December 2010, 79 patients with endometriosis
      related infertility underwent conservative laparoscopic surgery in Peking
      University First Hospital, including 16 cases with deep infiltrating
      endometriosis, 39 cases with ovarian endometriosis and 24 cases with peritoneal
      endometriosis. At 1 to 5 years follow-up after surgery, natural pregnancy outcome
      and recurrence were studied. RESULTS: (1) The accumulated pregnancy rate were
      6/16 in deep infiltrating endometriosis group, 36% (14/39) in ovarian
      endometriosis group, and 46% (11/24) in peritoneal endometriosis group, which did
      not reached statistical difference (P > 0.05). (2) The median interval between
      pregnancy and surgery were 38.5 months in deep infiltrating endometriosis group,
      9.5 in ovarian endometriosis group and 6.0 months in peritoneal endometriosis
      group. The median interval in deep infiltrating endometriosis was significantly
      longer than that in peritoneal endometriosis group and ovarian endometriosis
      group (P < 0.01). Total of 11 patients in peritoneal endometriosis group and 11
      patients in ovarian endometriosis group acquired pregnancy at 18 months after
      surgery. (3) The recurrent rate were 5/16 in deep infiltrating endometriosis
      group, 13% (5/39) in ovarian endometriosis group and 4% (1/24) peritoneal
      endometriosis group, respectively (P > 0.05). CONCLUSIONS: There was no
      difference among these three groups in accumulated pregnancy rate. However, the
      interval between pregnancy and surgery was significantly longer in patients with
      deep infiltrating endometriosis when compared with those in the other groups.

PMID- 23531247
TI  - [Investigation of iron deficiency status in the newborns of gestational diabetes
      mellitus women].
AB  - OBJECTIVE: To investigate the iron status in the newborns of maternal gestational
      diabetes mellitus (GDM) women, and explore the mechanism of iron deficiency in
      these newborns. METHODS: From June 2008 to October 2011, 64 GDM women (GDM group)
      and 71 healthy pregnant women (control group) who delivered in the Second
      Affiliated Hospital of Wenzhou Medical College and their newborns were studied
      prospectively. Serum ferritin (SF), serum transferrin receptor (sTfR),
      erythropoietin (Epo), haemoglobin (Hb), serum level of insulin and plasma glucose
      in cord blood was measured. The neonatal birth weight (BW) and birth weight Z
      Score (WAZ) was recorded. The concentrations of serum fasting insulin (FINS),
      fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were tested for
      all the women before delivery. RESULTS: In the GDM group, the cord blood sTfR,
      Epo and serum level of insulin was (42 +/- 10) nmol/L, (56 +/- 41) U/L and (18 +/
      5) U/L, respectively. While in the control group, these were (35 +/- 8) nmol/L,
      (41 +/- 43) U/L and (10 +/- 5) U/L, respectively. The cord blood sTfR, Epo and
      serum level of insulin in the GDM group were significantly higher than those in
      the control group (P < 0.05). The cord blood SF in the GDM group [(60 +/- 36)
      ug/L] was significantly lower than that of the control group [(146 +/- 38) ug/L,
      P < 0.01]. The neonatal BW and WAZ in the GDM group [(3615 +/- 538) g and 0.558]
      were significantly higher than those in the control group [(3449 +/- 423) g and
      0.224, P < 0.05]. No significant difference was found in the cord blood plasma
      glucose and Hb between the GDM group [(3.3 +/- 1.0) mmol/L and (181 +/- 18) g/L]
      and the control group [(3.0 +/- 0.8) mmol/L and (176 +/- 16) g/L, P > 0.05]. The
      FINS and HbA1c of the GDM group [(12.5 +/- 5.0) U/L and (6.5 +/- 0.7)%] were
      significantly higher than those in the control group [(10.9 +/- 4.3) U/L and (5.3
      +/- 0.7)%, P < 0.05]. The FPG of the GDM group and the control group were (5.3 +/
      1.2) and (5.0 +/- 1.0) mmol/L, respectively, with no statistically significant
      difference (P > 0.05). CONCLUSION: Maternal GDM may related to the iron
      deficiency of the newborns.

PMID- 23531248
TI  - [Effect of transforming growth factor beta1 on the expression of matrix
      metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and nuclear factor
      kappa B signalling pathway in the human amniotic cells WISH].
AB  - OBJECTIVE: To investigate the effect of transforming growth factor beta1 (TGF
      beta1) on the expression of matrix metalloproteinase 9 (MMP-9), tissue inhibitor
      of metalloproteinase 1 (TIMP-1), nuclear factor kappa B (NF-kappaB) and the
      possible signalling pathways in human amniotic cells WISH. METHODS: The WISH cell
      line was cultured. WISH cells were added with TGF-beta1 of different
      concentrations (0, 2, 10 and 20 ng/ml, respectively) for 24 hours. Then, reverse
      transcription (RT) PCR and western blotting were used to analyze the protein and
      mRNA expression of TIMP-1 and MMP-9; and the expression of NF-kappaB was analyzed
      by western blot. RESULTS: (1) The profile of TIMP-1 mRNA (0.413 +/- 0.036, 0.623
      +/- 0.058, 1.392 +/- 0.124, 1.387 +/- 0.102) in WISH cells elevated when the
      concentration of TGF-beta1 increased (0, 2, 10, 20 ng/ml). In accordance with
      TIMP-1 mRNA, the expression of TIMP-1 also elevated with the increase of TGF
      beta1 (0.357 +/- 0.031, 0.596 +/- 0.048, 1.243 +/- 0.097 and 1.359 +/- 0.121,
      respectively). And when 2, 10 or 20 ng/ml of TGF-beta1 was added, the TIMP-1 mRNA
      and protein were significantly higher than the TIMP-1 mRNA and protein when no
      TGF-beta1 was added (P < 0.05). (2) In contrast with TIMP-1, MMP-9 mRNA (1.325 +/
      0.056, 0.987 +/- 0.081, 0.610 +/- 0.034, 0.347 +/- 0.023) in WISH cells
      decreased when the concentration of TGF-beta1 increased (0, 2, 10, 20 ng/ml). The
      MMP-9 protein (1.119 +/- 0.064, 1.008 +/- 0.052, 0.578 +/- 0.041, 0.401 +/-
      0.015) also decreased with the increase of TGF-beta1. And when 2, 10 or 20 ng/ml
      of TGF-beta1 was added, the MMP-9 mRNA and protein were significantly lower than
      the MMP-9 mRNA and protein when no TGF-beta1 was added (P < 0.05). (3) The NF
      kappaB protein (1.423 +/- 0.065, 1.116 +/- 0.045, 0.796 +/- 0.041, 0.359 +/-
      0.021) was significantly reduced with the increase of TGF-beta1 (0, 2, 10, 20
      ng/ml;P < 0.05). CONCLUSIONS: The mRNA and protein expression of TIMP-1 decreased
      when TGF-beta1 was low in WISH cells, whereas those of MMP-9 elevated when TGF
      beta1 was low. The unbalance of TIMP-1 and MMP-9 was related to the pathology of
      the premature rupture of membrane. And the NF-kappaB singalling pathway might be
      an important mechanism in the regulation of TIMP-1 and MMP-9 system.

PMID- 23531249
TI  - [Impact of the biological function on epithelial ovarian cancer with ITIH4 gene
      expression down-regulating in vitro].
AB  - OBJECTIVE: To investigate the efficiency of biology function of ITIH4 gene
      silenced by small interfering RNA (siRNA) on ovarian cancer. METHODS: The four
      pairs ITIH4 gene siRNA interference fragments (ITIH4-546, ITIH4-795, ITIH4-917
      and ITIH4-1568) were designed respectively, and transfected into HO8910pm cells
      with ITIH4 mRNA high expression by liposomal method transiently. Quantitative PCR
      method was used to detect the ITIH4 mRNA expression in HO8910pm cells transfected
      with interference fragment. The ITIH4 917 was selected as the best silencing
      effect of siRNA interference fragment and then the recombinant plasmid expression
      vector pGPU6/GFP/Neo-shRNA-ITIH4-917 was constructed and transfected into
      HO8910pm cells. The stably transfected cells- pGPU6/GFP/Neo-shRNA-ITIH4-917
      HO8910pm cells was obtained by screening of aminoglycoside antibiotics (G418).
      The experiment was divided into three groups, namely ITIH4-917 transfection
      group, the HO8910pm cell group transfected with pGPU6/GFP/Neo-shRNA plasmid
      (empty vector group), and the HO8910pm cell group transfected with pGPU6/GFP/Neo
      shRNA-ITIH4-NC the plasmid (negative control group). Fluorescence quantitative
      reverse transcription (RT) PCR and western blot were used to detect the ITIH4
      mRNA and protein expression. The cell proliferation, the cell cycle, colony
      formation of cells, cells migration and invasion in vitro were determined by
      using methyl thiazolyl tetrazolium (MTT), flow cytometry, colony formation assay
      and transmembrane (transwell) small chamber method [value represented by
      absorbance (A)], respectively. RESULTS: The fluorescent quantitative PCR results
      showed that the ITIH4 mRNA expression levels in ITIH4-917 HO8910pm cells was
      significantly lower than that in the control cells, the relative copy number was
      only 0.26 +/- 0.15. Also the relative copy number of ITIH4 mRNA in ITIH4-917
      transfection group cells was 0.34 +/- 0.10, it significantly lower than that in
      empty vector group (1.87 +/- 0.12, P = 0.008) and negative control group (1.58 +/
      0.21, P = 0.032); Western blot results showed that the ITIH4 relative expression
      levels of the protein in ITIH4-917 HO8910pm group cells, empty vector group and
      negative control group were 0.51, 1.64 and 1.74, respectively, there were
      statistically significant differences (0.51 vs. 1.64, P = 0.012; 0.51 vs. 1.74, P
      = 0.014). MTT colorimetric assay showed that the proliferation of ITIH4-917
      HO8910pm group cells was significantly faster than that in the empty vector group
      and negative control group, and there were statistically significant differences
      among them (P = 0.001). The S + G2/M phase cell ratio in ITIH4-917 HO8910pm group
      cells was 54.2%, which was significantly higher than that in the empty vector
      group or negative control group (26.3% and 31.3%, respectively, all P < 0.05).
      The colony formation rate (55.7 +/- 0.7)% in ITIH4-917 HO8910pm group cells was
      also significantly higher than that in empty vector group (29.7 +/- 0.9)% (P =
      0.037) and negative control group (31.4 +/- 0.3)% (P = 0.043). Migration and
      invasion experiments showed that cell migration in ITIH4-917 HO8910pm group cells
      was 0.40 +/- 0.18, whicht was significantly higher than that in the negative
      control group or empty vector (0.30 +/- 0.03, P = 0.031;0.25 +/- 0.03, P = 0.028,
      respectively). Although the invasive ability of ITIH4-917 HO8910pm group cells
      (1.31 +/- 0.34) was higher than that in the control cells (1.05 +/- 0.68) and
      empty vector group (1.14 +/- 0.08), while there were not significant difference
      (P > 0.05). CONCLUSION: It would be to promote the cell doubling time and
      increase the migration capability in HO8910pm cells that ITIH4 expression was
      down-regulating by ITIH4 mRNA interference.

PMID- 23531250
TI  - [Role of endoplasmic reticulum protein folding molecular chaperones in
      floxuridine-resistance choriocarcinoma JeG-3/FUDRA cell line].
AB  - OBJECTIVE: To investigate changes of protein expression profiles between human
      choriocarcinoma JeG-3 cell line and its floxuridine (FUDR)-resistant sub-line.
      METHODS: The differentially expressed proteins were identified by using two
      dimension difference gel electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) approaches.
      Gene ontology (GO) analysis and Pathway analysis were used to screen the
      candidate proteins. The levels of the proteins in chemo-resistant sub-lines were
      validated by western blot. Ribonucleic acid interference (RNAi) was used to
      knockdown the expression of calreticulin (CALR) and (or) protein disulfide
      isomerase A3 (PDIA3) respectively. RESULTS: Forty-six proteins spots were found
      to be significantly different in spot intensity by statistical analysis between
      chemo-resistance sub-line and parent cell line, of which 31 proteins were
      identified by MALDI-TOF-MS. Comparing to the parent cell lines, three endoplasmic
      reticulum (ER) protein folding molecular chaperones: CALR, PDIA3 and 78 000
      glucose-regulated protein (GRP78) screened out were increased significantly in
      floxuridine-resistant sub-line and were verified by western blot. The resistance
      index decreased by knockdown the CALR and/or PDIA3 expression in FUDR-resistant
      sub-line 76.3% (36.7 +/- 2.0 vs. 8.7 +/- 3.1, P < 0.05) and 51.4% (36.7 +/- 2.0
      vs. 17.8 +/- 1.2, P < 0.05) respectively. CONCLUSION: These ER protein folding
      molecular chaperones, CALR, PDIA3 and GRP78, may involved in the mechanism of
      FUDR-resistance choriocarcinoma.

PMID- 23531251
TI  - [Effect of aurora kinase B inhibitor AZD1152 in the treatment of cisplatin
      resistant ovarian carcinoma].
AB  - OBJECTIVE: To investigate whether AZD1152 (AZD), the selective inhibitor of
      aurora kinase B, may play a role in the treatment of cisplatin-resistant ovarian
      carcinoma when administrated alone or in combination with cisplatin. METHODS: Hey
      (cisplatin-resistant ovarian cancer cell line) cells were analyzed. According to
      the treatment plan, Hey cells were divided into four groups (AZD group, cisplatin
      group, AZD + cisplatin group and control group). Methyl thiazolyl tetrazolium
      (MTT) assay was used to test the cells proliferation, caspase-3/7 activity
      analysis was used to analyze cells apoptosis, and fluorescence in-situ
      hybridization (FISH) assay was used to determine the copy the number of
      chromosome 7 and checked the copy numbers of hTERC gene and C-myc gene. RESULTS:
      MTT test showed that proliferation of AZD group was lower than that in control
      group (P < 0.01). The cells proliferation with the treatment with 10 and 20
      nmol/L AZD for 24 hours was (81.4 +/- 3.6)% and (81.4 +/- 3.6)% respectively, and
      the cells proliferation for 48 hours was (43.1 +/- 2.0)% and (38.5 +/- 1.6)%
      respectively, which was significantly lower than control group (100%, P < 0.01);
      Treated with the same concentration of AZD, inhibition of proliferation was
      significantly enhanced as the time extended (P < 0.01). Proliferation in group
      AZD + cisplatin was lower than that in cisplatin group (P < 0.01) which suggest
      that there were additive effects after combined AZD with cisplatin. Compared with
      control group, caspase-3/7 activity in AZD group increased significantly (P =
      0.000), and the same results was seen between AZD + cisplatin group and cisplatin
      group or AZD group (all P < 0.01). Compared with cisplatin group or control
      group, the copy numbers of hTERC, C-myc and the number of chromosome were
      significantly increased in AZD group and AZD + cisplat group (all P < 0.05).
      CONCLUSIONS: AZD could inhibit ovarian cancer cells proliferation and induce
      cells apoptosis significantly. AZD alone or in combination with cisplatin may
      result in the increased cells polyploidy.

PMID- 23531252
TI  - Impact of enzyme replacement therapy on survival in adults with Pompe disease:
      results from a prospective international observational study.
AB  - BACKGROUND: Pompe disease is a rare metabolic myopathy for which disease-specific
      enzyme replacement therapy (ERT) has been available since 2006. ERT has shown
      efficacy concerning muscle strength and pulmonary function in adult patients.
      However, no data on the effect of ERT on the survival of adult patients are
      currently available. The aim of this study was to assess the effect of ERT on
      survival in adult patients with Pompe disease. METHODS: Data were collected as
      part of an international observational study conducted between 2002 and 2011, in
      which patients were followed on an annual basis. Time-dependent Cox's
      proportional hazards models were used for univariable and multivariable analyses.
      RESULTS: Overall, 283 adult patients with a median age of 48 years (range, 19 to
      81 years) were included in the study. Seventy-two percent of patients started ERT
      at some time during follow-up, and 28% never received ERT. During follow-up
      (median, 6 years; range, 0.04 to 9 years), 46 patients died, 28 (61%) of whom had
      never received ERT. After adjustment for age, sex, country of residence, and
      disease severity (based on wheelchair and ventilator use), ERT was positively
      associated with survival (hazard ratio, 0.41; 95% CI, 0.19 to 0.87). CONCLUSION:
      This prospective study was the first to demonstrate the positive effect of ERT on
      survival in adults with Pompe disease. Given the relatively recent registration
      of ERT for Pompe disease, these findings further support its beneficial impact in
      adult patients.

PMID- 23531253
TI  - Personal, behavioral and socio-environmental predictors of overweight incidence
      in young adults: 10-yr longitudinal findings.
AB  - BACKGROUND: The objective of this study was to identify 10-year longitudinal
      predictors of overweight incidence during the transition from adolescence to
      young adulthood. METHODS: Data were from Project EAT (Eating and Activity in
      Teens and Young Adults). A diverse, population-based cohort (N = 2,134) completed
      baseline surveys in 1998-1999 (mean age = 15.0+/-1.6, 'adolescence') and follow
      up surveys in 2008-2009 (mean age = 25.4+/-1.7, 'young adulthood'). Surveys
      assessed personal, behavioral and socio-environmental factors hypothesized to be
      of relevance to obesity, in addition to height and weight. Multivariable logistic
      regression was used to estimate the adjusted odds for each personal, behavioral
      and socio-environmental factor at baseline, and 10-year changes for these
      factors, among non-overweight adolescents (n = 1,643) being predictive of the
      incidence of overweight (BMI >= 25) at 10-year follow-up. RESULTS: At 10-year
      follow-up, 51% of young adults were overweight (26% increase from baseline).
      Among females and males, higher levels of body dissatisfaction, weight concerns,
      unhealthy weight control behaviors (e.g., fasting, purging), dieting, binge
      eating, weight-related teasing, and parental weight-related concerns and
      behaviors during adolescence and/or increases in these factors over the study
      period predicted the incidence of overweight at 10-year follow-up. Females with
      higher levels of whole grain intake and breakfast and dinner consumption
      frequency during adolescence were protected against becoming overweight. Among
      males, increases in vegetable intake protected against the incidence of
      overweight 10 years later. CONCLUSIONS: Findings suggest that obesity prevention
      interventions for adolescents should address weight-specific factors from within
      the domains of personal, behavioral, and socio-environmental factors such as
      promoting positive body image, decreasing unhealthy weight control behaviors, and
      limiting negative weight talk.

PMID- 23531254
TI  - Role of alcohol in hospitalized road trauma in Viet nam.
AB  - OBJECTIVE: To assess the blood alcohol concentration (BAC; dependent variable) of
      patients with road traffic injuries (RTIs) presenting at 3 provincial and central
      hospitals in the Socialist Republic of Viet Nam by age, sex, and road user type
      (independent variables). This survey formed part of the Viet Nam Road Traffic
      Injury Prevention Project, funded by Bloomberg Philanthropies. INTRODUCTION: RTIs
      are a leading cause of death and disability in Viet Nam, with 14,690 deaths and
      143,940 injuries reported by the Ministry of Health (MOH) in 2010. Research
      estimates suggest that motorcycle riders and passengers account for 60 percent of
      fatalities. Alcohol has long been suspected of being a leading cause of road
      traffic collisions and injuries. However, until now data on this relationship
      have been limited. METHODS: A descriptive cross-sectional study measuring BAC in
      all consenting patients with RTIs presenting at 3 provincial or central hospitals
      between July 2009 and September 2010. All results were anonymous and summary
      information on key variables was sent to MOH and the World Health Organization
      (WHO) on a monthly basis. RESULTS: Of the 36,418 patients with RTIs presenting to
      these 3 hospitals between July 2009 and September 2010, BAC analysis was
      completed on 14,990 patients (41.2%), representing all patients with RTIs 15
      years of age and above who consented to anonymous testing. BAC results ranged
      from 0 to 0.589 g/dL blood, with a mean of 0.0441 g/dL being the average
      concentration among all tested patients. Of all patients tested, 56.8 percent had
      no detectable alcohol in their system. Motorcycle riders were most commonly
      represented in the tested sample (70.7%), with 27.8 percent having a BAC above
      the legal limit (0.05 g/dL). Car or other vehicle drivers represented 2.7 percent
      of the sample, with 63.4 percent tested having a BAC above 0 g/dL, the legal
      limit for these road users. CONCLUSIONS: The results of this preliminary study
      indicate that 29.1 percent of all car drivers and motorcycle riders presenting at
      hospitals with RTIs exceeded the legal BAC limit for operating a motor vehicle.
      Though further study is required, this is suggestive that strengthening the
      enforcement of drink-driving laws is an urgent national road safety priority.

PMID- 23531255
TI  - Scooter crashes at university: intervention tactics for modified behavior and
      helmet use.
AB  - OBJECTIVE: Mopeds and scooters are defined as 2-wheeled vehicles with engine
      displacement ranging from 49 to 250 cm(3). These vehicles have experienced a
      resurgence in modern culture and are especially popular on large university
      campuses. Increased operation of mopeds and scooters has been a contributor to
      increased accidents and in some cases fatalities. Available statistics indicate
      that a majority of individuals involved in scooter crashes were not wearing
      helmets. The objective of this study was to explore perceptions of helmets and
      the significance of behavioral intention related to attitude toward helmet use
      among operators of these potentially dangerous motor vehicles. METHODS: The study
      collected a sample from the general population of scooter operators on a major
      southeastern university campus (N = 151). Criteria examined included gender
      differences related to perception of helmet use, perception of helmet attributes
      (safety, price, appearance, comfort) as predictors of perceived risk, and
      behavioral intention (control beliefs, normative beliefs, and behavioral beliefs)
      as predictors of attitude toward helmet use. RESULTS: Many riders (41%) were
      inexperienced operators, did not wear helmets (65%), did not take a safety course
      (88.1%), and ignored traffic laws (56.3%). Women reported significantly higher
      levels of unpleasantness associated with helmet use than men. Regression analyses
      indicate that comfort and safety of helmets were significant predictors of
      perceived risk of injury. Length of ownership was significantly correlated to
      perception of safety. Normative beliefs and control beliefs were independent
      significant predictors of attitudes toward helmet use. CONCLUSIONS: University
      students who operated scooters were principally untrained in safe operation
      measures and in many cases ignored traffic laws. Though perceptions of helmets as
      a safety device were significant, they were viewed as uncomfortable, most often
      among female operators. Key psychological indicators of attitudes toward helmet
      use were perceived norms and control in making choices. The best course of action
      is messages that (1) introduces modern features that make helmets more user
      adaptable to comfort; (2) promote a positive outcome through users' motivation to
      comply to norms (i.e., parental influence); and (3) encourage the perceived
      empowerment that emanates from control in decision making.

PMID- 23531256
TI  - Driving performance and behaviors: a comparison of gender differences in
      Parkinson's disease.
AB  - OBJECTIVE: The primary objective of this study was to determine gender
      differences by comparing self-reported driving behaviors, clinical tests, and on
      road driving performance in a cohort of men and women drivers with Parkinson's
      disease (PD). METHODS: In this prospective observational study, we analyzed data
      of a convenience sample of 63 men (mean age = 70.9 +/- 6.6 years) and 21 women
      (mean age 67.1 +/- 7.3 years) with diagnosed PD. All participants underwent a
      comprehensive driving evaluation by a certified driving rehabilitation
      specialist. RESULTS: On average, both men and women were active drivers (driving
      ~4.6 times/week). A substantial proportion of both groups avoided driving at
      night (40% of men versus 46% of women), during rush hour, and in heavy traffic
      (36% of men versus 57% of women), although the differences were not significant.
      Both groups reported some avoidance behaviors: making left-hand turns (9.7% men
      versus 9.5% women), driving in the rain (12.9% men versus 19.0% women), or on the
      interstate/highway (14.3% men versus 7.7% women). With respect to driving
      performance, both groups were equally likely to fail the on-road test (42.6% men
      versus 42.9% women). Although men committed slightly more total driving errors
      compared to women, the differences were not statistically significant. Specific
      driving errors also did not differ by gender. Controlling for gender and disease
      severity, age was an independent predictor of total driving errors in men but not
      in women. Additionally, a cut-point of >=2.5 on the modified Hoehn and Yahr was
      predictive of pass-fail outcomes in men when controlling for age. CONCLUSIONS:
      Our study shows preliminary evidence that few gender differences exist with
      respect to driving errors and overall driving performance. Future studies should
      better balance gender distribution by age in PD driving studies to determine
      whether there are indeed differences in driving performance between men and
      women.

PMID- 23531257
TI  - A study on the relationship between personality and driving styles.
AB  - OBJECTIVE: Research on driving behavior and personality traits is a key factor in
      the development of driver-oriented safety interventions. However, research is
      fragmented and a multidimensional perspective is lacking. The primary aim of this
      study is to assess the multiple relationships between driving styles and
      personality traits using the alternative 5-factor model. A secondary goal is to
      determine whether these relationships vary by gender and age. METHODS: Data were
      collected from a sample of 908 Argentine drivers. Driving styles were assessed
      using the Multidimensional Driving Style Inventory. Personality was assessed with
      the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ-50-CC; Aluja et al. 2006)
      questionnaire. RESULTS: Different patterns of personality are associated with
      different driving styles. These relationships appear to be robust with respect to
      gender and age; however, in some cases these variables did influence the observed
      relationships. CONCLUSION: The results provide researchers with a more
      comprehensive understanding of the relationships between personality traits and
      driving styles. Practical prevention measures are discussed.

PMID- 23531258
TI  - Driving behaviors and on-duty road accidents: a French case-control study.
AB  - OBJECTIVES: A case-control study was carried out to identify driving behaviors
      associated with the risk of on-duty road accident and to compare driving
      behaviors according to the type of journey (on duty, commuting, and private) for
      on-duty road accident victims. METHODS: Cases were recruited from the Rhone Road
      Trauma Registry between January 2004 and October 2005 and were on duty at the
      time of the accident. Control subjects were recruited from the electoral rolls of
      the case subjects' constituencies of residence. Cases' and controls' driving
      behavior data were collected by self-administered questionnaire. A logistic
      regression was performed to identify behavioral risk factors for on-duty road
      accidents, taking into account age, sex, place of residence, road accident risk
      exposure, socio-occupational category, and type of road user. A second analysis
      focused specifically on the case subjects, comparing their self-assessed usual
      behaviors according to the type of journey. RESULTS: Significant factors for
      multivariate analysis of on-duty road accidents were female gender, history of on
      duty road accidents during the previous 10 years, severe time pressure at work,
      and driving a vehicle not belonging to the driver. On-duty road accident victims
      reported behavioral risk factors more frequently in relation to driving for work
      than driving for private reasons or commuting: nonsystematic seat belt use, cell
      phone use at least once daily while driving, and history of accidents with injury
      during the previous 10 years. CONCLUSIONS: This study provides knowledge on
      behavioral risk factors for on-duty road accidents and differences in behavior
      according to the type of journey for subjects who have been on-duty road accident
      victims. These results will be useful for the design of on-duty road risk
      prevention.

PMID- 23531259
TI  - Head injuries to restrained occupants in single-vehicle pure rollover crashes.
AB  - OBJECTIVE: Studies performed previously of seat-belted occupants in real-world
      passenger vehicle rollover-only crashes have identified the head as one of the
      body regions most often seriously injured. However, there have been few studies
      investigating how these head injuries occur in any detail. This study aims to
      investigate the characteristics and patterns of head injury to seat-belted
      occupants in real-world rollover-only crashes and to identify possible
      biomechanical mechanisms responsible for head injury to aid in the development of
      a dynamic rollover test protocol. METHODS: National Automotive Sampling System
      Crashworthiness Data System (NASS-CDS) data were used to generate summary
      statistics and perform logistic regression analysis of restrained and contained
      occupants in U.S. pure trip-over rollover crashes. Specific information from
      selected CDS cases focused on identifying potential mechanisms and patterns of
      serious head injury and the rollover conditions under which the injury occurred
      are also presented. RESULTS: Twenty-one percent of seriously injured occupants in
      pure trip-over rollovers had a serious head injury. On average, occupants seated
      on the far side of the rollover sustained serious head injuries more frequently
      and were more likely to receive injuries to the inboard side of the head than
      near-side occupants. Serious head injuries appear to be decoupled from serious
      injuries to other body regions except for a relationship found between basal
      skull fractures and cervical spine fractures. Serious head injuries were
      sustained by some occupants who had less than 15 cm of roof crush above their
      seated position. CONCLUSIONS: Serious brain injuries appear to occur frequently
      as a result of loading to the periphery of the head from contact with the roof
      assembly. Two mechanisms of injury for basal skull fractures in rollover crashes
      were identified. The injury patterns and locations of contact to the head are
      sensitive to the seated position of the occupant.

PMID- 23531260
TI  - Muscle activity influence on the kinematics of the cervical spine in rear-end
      sled tests in female volunteers.
AB  - OBJECTIVE: Although much research has been performed to investigate the cervical
      spine kinematics during rear-end collisions, our understanding about the exact
      role of the musculature is limited. The question of the influence of muscle
      activity on cervical spine kinematics has been discussed. METHODS: A rear-end
      collision with a speed change (DeltaV) of 6.3 km/h was simulated in a sled test
      with 8 female subjects to investigate the influence of the ventral and dorsal
      cervical spine musculature on cervical spine kinematics. A high-speed camera and
      accelerometers recorded the motion and acceleration data. The activity of the
      sternocleidomastoid muscles was recorded with surface electrodes. To avoid cross
      talk, an intramuscular recording of the semispinalis capitis muscles was
      performed with fine-wire electrodes. RESULTS: The analysis of the motion and
      acceleration parameters allowed the definition of 4 phases. The headrest contact
      began after a median of 84 ms and the sternocleidomastoid muscle force could be
      detected after a median of 81 ms, with 0 defining the time of the trigger signal.
      The maximal force of the sternocleidomastoid muscle and the maximal headrest
      effect began prior to the maximal ventral angular head acceleration and prior to
      the maximal ventral horizontal head acceleration relative to T1. The start of the
      semispinalis capitis muscle force was observed after a median of 159 ms and
      increased until a flexion of 20 to 25 degrees  was reached. CONCLUSIONS: The
      headrest effect and the sternocleidomastoid muscle force firstly supported the
      deceleration of the head relative to T1 toward dorsal, which was followed by an
      accelerating effect toward ventral. The semispinalis capitis muscle force exerted
      a late decelerating effect on head flexion and ventral translation movement.

PMID- 23531261
TI  - Coupling lateral bending and shearing mechanisms to define knee injury criteria
      for pedestrian safety.
AB  - OBJECTIVE: In car-pedestrian accidents, lateral bending and shearing kinematics
      have been identified as principal injury mechanisms causing permanent
      disabilities and impairments to the knee joint. Regarding the combined lateral
      bending and shearing contributions of knee joint kinematics, developing a coupled
      knee injury criterion is necessary for improving vehicle countermeasures to
      mitigate pedestrian knee injuries. METHODS: The advantages of both experimental
      tests and finite element (FE) simulations were combined to determine the reliable
      injury tolerances of the knee joint. First, 7 isolated lower limb tests from
      postmortem human subjects (PMHS) were reported, with dynamic loading at a
      velocity of 20 km/h. With the intention of replicating relevant injury mechanisms
      of vehicle-pedestrian impacts, the experimental tests were categorized into 3
      groups by the impact locations on the tibia: the distal end to prioritize pure
      bending, the middle diaphysis to have combined bending and shearing effects, and
      the proximal end to acquire pure shearing. Then, the corresponding FE model was
      employed to provide an additional way to determine exact injury occurrences and
      develop a robust knee injury criterion by the variation in both the lateral
      bending and shearing contributions through a sensitivity analysis of impact
      locations. RESULTS: Considering the experimental test results and the subsequent
      sensitivity analysis of FE simulations, both the tolerances and patterns of knee
      joint injuries were determined to be influenced by impact locations due to
      various combined contributions of lateral bending and shearing. Both medial
      collateral ligament and cruciate ligament failures were noted as the onsets of
      knee injuries, namely, initial injuries. Finally, a new injury criterion
      categorized by initial injury patterns of knee joint was proposed by coupling
      lateral bending and shearing levels. CONCLUSIONS: The developed injury criterion
      correlated the combined joint kinematics to initial knee injuries based on
      subsegment tests and FE simulations conducted with a biofidelic lower limb model.
      This provides a valuable way of predicting the risk of knee injury associated
      with vehicle-pedestrian crashes and thereby represents a further step to promote
      the design of vehicle countermeasures for pedestrian safety.

PMID- 23531262
TI  - The impact of new legislation on child restraint system (CRS) misuse and
      inappropriate use in Australia.
AB  - OBJECTIVE: The current study aimed to investigate the incidence of child
      restraint system (CRS) misuse and/or inappropriate use of CRS through an
      Australian CRS inspection program conducted by CRS fitting specialists between
      October 2004 and October 2011 and to determine whether CRS misuse and/or
      inappropriate use of CRS changed following new Australian legislation regarding
      CRS and motor vehicle restraint use for children aged 7 years and under. METHODS:
      Participants were recruited through an advertisement for free CRS inspections
      displayed at childcare centers, kindergartens, community centers, hospitals, and
      child expos. At each inspection, a CRS fitting specialist inspected each child in
      their CRS while in their vehicle and reported to the owner of the CRS on the
      installation of the child restraint(s) and/or system(s) and any fitting faults
      and/or concerns with the fitting and/or use of the child restraint(s) and or
      system(s). RESULTS: Results are based on the inspection of 2674 CRS. Of all of
      the CRS inspected, the majority (79%) were reported as having at least one
      instance of misuse and/or inappropriate use. The most common forms of CRS misuse
      and/or inappropriate use observed were harness strap errors (twisted, poorly
      adjusted, and/or incorrectly positioned, 41%), seat belt errors (incorrectly
      routed, twisted, and/or incorrectly adjusted, 32%), and a missing or incorrect
      fitting of the gated buckle/locking clip (24%). Significant differences were
      found across the proportion of CRS misuse and/or inappropriate use across
      restraint types (infant restraint/forward-facing CRS/convertible [birth to 18 kg]
      CRS/convertible [8-26 kg] CRS/boosters [booster seat/cushion/booster with harness
      combination]), chi(2)(4) = 147.852, P < .001. CRS misuse and/or inappropriate use
      were most prevalent among convertible CRS (birth to 18 kg; 87%), forward-facing
      CRS (85%), and convertible CRS (8-26 kg; 81%), compared to infant restraints
      (73%) and booster seats (booster seats/cushions/boosters with H-harness
      combination; 65%). There was no significant difference in the proportion of CRS
      with misuse and/or inappropriate use across the pre- and post-legislation period
      (80% vs. 77%), chi(2)(1) = 1.545, P > .5. CONCLUSIONS: Based on the findings of
      the current study, it was concluded that, despite the introduction of new,
      definitive CRS legislation, CRS misuse and/or inappropriate use remains
      widespread in Australia. The findings highlight the need for CRS education and
      legislation that include information on correct CRS use, as well as information
      on appropriate CRS use, in order to provide specialized protection for child
      vehicle occupants in the event of a motor vehicle crash.

PMID- 23531263
TI  - A simulation study of spine biofidelity in the hybrid-III 6-year-old ATD.
AB  - OBJECTIVE: Because of the lack of pediatric biomechanical data, Hybrid-III (HIII)
      child anthropomorphic test devices (ATDs) are essentially scaled from the mid
      size male ATD based on the geometric considerations. These ATDs inherit a rigid
      thoracic spine from the adult HIII ATDs, which has been criticized as
      unrealistic. Therefore, the objective of this study was to explore possible
      design modifications for improving the spine biofidelity of the HIII 6-year-old
      ATD. METHODS: A previously developed and validated HIII 6-year-old MADYMO ATD
      model was used as the baseline model to investigate the effects of design
      modifications on the spine biofidelity of the current ATD. Several sets of child
      volunteer and cadaver test data were considered as the design targets, including
      child volunteer low-speed crash test data, pediatric cadaver cervical spine
      tensile test data, and child cadaver crash test data. ATD design modifications
      include adding an additional joint to the thoracic spine region and changing the
      joint characteristics at the cervical and lumbar spine regions. Optimization
      techniques were used to match simulation results to each set of test results.
      RESULTS: The results indicate that the translational characteristics of the
      cervical and lumbar spine in the current child ATD need to be reduced to achieve
      realistic spine flexibility. Adding an additional joint at the thoracic spine
      region with degree of freedom in both flexion/extension and tension would
      significantly improve the ATD biofidelity in terms of predicting the overall
      spine curvature and head excursion in frontal crashes. CONCLUSIONS: Future ATD
      spine modification should focus on reducing the neck and lumbar tension stiffness
      and adding additional flexibility both in flexion/extension and tension at the
      thoracic spine region. The child ATD model developed in this study can be used as
      an important tool to improve child ATD biofidelity and child restraint system
      design in motor vehicle crashes.

PMID- 23531264
TI  - Altering school attendance times to prevent child pedestrian injuries.
AB  - OBJECTIVES: The purpose of this research was to determine whether modifying
      school start time schedules can be used to reduce children's exposure to traffic
      on their morning walks to school. METHODS: We use models of pedestrian and motor
      vehicle commuting to estimate the frequency of encounters between child
      pedestrians and motor vehicles at intersections throughout the City of Hamilton,
      Ontario, Canada. We use a simple heuristic to identify the school-specific start
      times that would most reduce the local frequency of encounters between motor
      vehicles and pedestrians. RESULTS: Our analysis suggests that it may be possible
      to achieve an almost 15 percent reduction in the total number of encounters
      between child pedestrians and motor vehicles during the morning commute by
      staggering school start times such that the periods of high pedestrian activity
      are temporally staggered from periods of high motor vehicle activity. Our
      analysis suggests that small changes in school start times could be sufficient to
      see noteworthy reductions in pedestrian exposure to traffic. CONCLUSIONS:
      Changing school times may be an effective, inexpensive, and practical tool for
      reducing child pedestrian injuries in urban environments. Enhanced transportation
      models and community-based interventions are natural next steps for exploring the
      use of school-specific scheduling to reduce the risk of child pedestrian injury.
      Further research is required to validate our models before this analysis should
      be used by policy makers.

PMID- 23531265
TI  - Effects of simulated day and night driving on the speed differential in tangent
      curve transition: a pilot study using driving simulator.
AB  - OBJECTIVE: The pilot study described in this article aimed to analyze the driver
      speed profile for evaluation of road design consistency during simulated day and
      nighttime driving. The research, carried out using a driving simulator, was
      developed with the overall objectives of evaluating the speed differential during
      simulated nighttime driving for the identification of critical road situations
      not detected by design consistency evaluation during simulated daytime driving.
      METHODS: An existing 2-lane rural road, where high accident rates were recorded
      during nighttime, was implemented in the driving simulator of the Inter
      University Research Centre of Road Safety (CRISS) and the drivers' speed profiles
      were recorded in both simulated day and nighttime driving conditions over the 39
      tangent-curve configurations that composed the road alignment. RESULTS: The
      analysis of the speed differential based on the 85MSR (Maximum Speed Reduction)
      indicator during simulated daytime driving was not able to identify critical road
      situations that the same analysis revealed during the simulated nighttime
      driving. Such results occurred for most of the tangent-curve configurations.
      CONCLUSIONS: The study demonstrated that limiting the speed analysis only to
      daytime driving conditions cannot exclude the possibility that during nighttime
      driving some road configurations could become unsafe. The findings of the study
      highlight the need to carry out design consistency evaluations for nighttime
      driving conditions.

PMID- 23531266
TI  - A method for determining the number of traffic conflict points between vehicles
      at major-minor highway intersections.
AB  - BACKGROUND: Traffic conflict points are the areas formed by conflict movements in
      the traffic flow. The numbers and distributions of different types of traffic
      conflict points are often used to evaluate access management designs and the
      safety performance of intersections. Customarily, determining the number of
      different types of traffic conflict points is based on the manual drawing method,
      which is troublesome and makes using computerized procedures for calculation of
      the number of traffic conflict points difficult. OBJECTIVE: The present work aims
      to quickly compute the number of traffic conflict points between vehicles at
      major-minor highway intersections. METHODS: The concept of "virtual lanes" is
      defined, and the virtual lane conversion method is proposed. Based on actual and
      virtual lanes, vehicular movements, and traffic control modes, a generalized
      method to determine the number of traffic conflict points between vehicles at
      major-minor highway intersections is developed. RESULTS: A procedure for
      determining the number of conflict points is presented. A similar HCM LOS-style
      form and computer software were designed to help calculate the number of conflict
      points. CONCLUSIONS: Applications show that the method can efficiently and
      accurately determine the number of traffic conflict points between vehicles at
      major-minor highway intersections.

PMID- 23531267
TI  - The effects of peer influence on adolescent pedestrian road-crossing decisions.
AB  - OBJECTIVE: Adolescence is a high-risk period for pedestrian injury. It is also a
      time of heightened susceptibility to peer influence. The aim of this research was
      to examine the effects of peer influence on the pedestrian road-crossing
      decisions of adolescents. METHODS: Using 10 videos of road-crossing sites, 80 16-
      to 18-year-olds were asked to make pedestrian road-crossing decisions.
      Participants were assigned to one of 4 experimental conditions: negative peer
      (influencing unsafe decisions), positive peer (influencing cautious decisions),
      silent peer (who observed but did not comment), and no peer (the participant
      completed the task alone). Peers from the adolescent's own friendship group were
      recruited to influence either an unsafe or a cautious decision. RESULTS:
      Statistically significant differences were found between peer conditions.
      Participants least often identified safe road-crossing sites when accompanied by
      a negative peer and more frequently identified dangerous road-crossing sites when
      accompanied by a positive peer. Both cautious and unsafe comments from a peer
      influenced adolescent pedestrians' decisions. CONCLUSIONS: These findings showed
      that road-crossing decisions of adolescents were influenced by both unsafe and
      cautious comments from their peers. The discussion highlighted the role that
      peers can play in both increasing and reducing adolescent risk-taking.

PMID- 23531268
TI  - PPh3-derivatives of [Pt3n(CO)6n]2- (n = 2-6) Chini's clusters: syntheses,
      structures, and 31P NMR studies.
AB  - The reaction of the [Pt3n(CO)6n](2-) (n = 2-6) Chini's clusters with increasing
      amounts of PPh3 has been investigated in detail by combined FT-IR, (31)P{(1)H}
      NMR, and electrospray ionization-mass spectrometry (ESI-MS) studies, showing that
      up to three CO ligands are gradually substituted by PPh3, resulting in isonuclear
      phosphine-substituted anionic clusters of general formula [Pt3n(CO)(6n
      x)(PPh3)(x)](2-) (n = 2-6; x = 1-3). Further addition of PPh3 results in the
      elimination of the neutral Pt3(CO)3(PPh3)3 species and formation of lower
      nuclearity anionic clusters. [Pt12(CO)22(PPh3)2](2-) and [Pt9(CO)16(PPh3)2](2-)
      have been structurally characterized, and they maintain the trigonal prismatic
      structures of the parent homoleptic clusters, with the two PPh3 ligands bonded to
      different external Pt3-triangles in relative cis-position. Conversely, the
      crystal structure of [Pt6(CO)10(PPh3)2](2-) shows that its metal cage is
      transformed from trigonal prismatic to trigonal antiprismatic after CO/PPh3
      exchange.

PMID- 23531269
TI  - Patient-ventilator asynchronies: may the respiratory mechanics play a role?
AB  - INTRODUCTION: The mechanisms leading to patient/ventilator asynchrony has never
      been systematically assessed. We studied the possible association between
      asynchrony and respiratory mechanics in patients ready to be enrolled for a home
      non-invasive ventilatory program. Secondarily, we looked for possible differences
      in the amount of asynchronies between obstructive and restrictive patients and a
      possible role of asynchrony in influencing the tolerance of non-invasive
      ventilation (NIV). METHODS: The respiratory pattern and mechanics of 69
      consecutive patients with chronic respiratory failure were recorded during
      spontaneous breathing. After that patients underwent non-invasive ventilation for
      60 minutes with a "dedicated" NIV platform in a pressure support mode during the
      day. In the last 15 minutes of this period, asynchrony events were detected and
      classified as ineffective effort (IE), double triggering (DT) and auto-triggering
      (AT). RESULTS: The overall number of asynchronies was not influenced by any
      variable of respiratory mechanics or by the underlying pathologies (that is,
      obstructive vs restrictive patients). There was a high prevalence of asynchrony
      events (58% of patients). IEs were the most frequent asynchronous events (45% of
      patients) and were associated with a higher level of pressure support. A high
      incidence of asynchrony events and IE were associated with a poor tolerance of
      NIV. CONCLUSIONS: Our study suggests that in non-invasively ventilated patients
      for a chronic respiratory failure, the incidence of patient-ventilator
      asynchronies was relatively high, but did not correlate with any parameters of
      respiratory mechanics or underlying disease.

PMID- 23531270
TI  - A molecular investigative approach to an outbreak of acute hemorrhagic
      conjunctivitis in Egypt, October 2010.
AB  - BACKGROUND: During October 2010, Egypt reported an outbreak of acute hemorrhagic
      conjunctivitis (AHC). A total of 1831 cases were reported from three
      governorates; 1703 cases in El Daqahliya, 92 cases in Port Said, and 36 in
      Damietta. The purpose of this study was to identify and characterize the
      causative agent associated with this outbreak. METHODS: The U.S. Naval Medical
      Research Unit No.3 (NAMRU-3) was contacted by the Egyptian Ministry of Health and
      Population to perform diagnostic laboratory testing on eighteen conjunctival
      swabs from patients with conjunctivitis from El Daqahliya Governorate.
      Conjunctival swabs were tested by molecular methods for human adenovirus (HAdV)
      and enteroviruses (EV). Virus isolation was performed; the isolated virus was
      further characterized by molecular typing and phylogenetic analysis. RESULTS: The
      majority of the samples (17/18) were positive for enterovirus and all were
      negative for HAdV. Molecular typing and sequencing of the isolated virus revealed
      the presence of coxsackievirus A24 variant. Phylogenetic analysis based on the
      VP1 and 3C regions demonstrated that the Egyptian viruses belonged to Genotype IV
      and are closely related to coxsackievirus A24 variant, reported in a similar
      outbreak in China in August 2010. CONCLUSIONS: This study strongly suggests that
      coxsackievirus A24 variant was associated with the acute hemorrhagic
      conjunctivitis outbreak reported in Egypt in October 2010. There is a possibility
      that the same strain of CV-A24v was implicated in the AHC outbreaks in both China
      and Egypt in 2010.

PMID- 23531271
TI  - Cardiovascular medicine at face value: a qualitative pilot study on clinical
      axiology.
AB  - INTRODUCTION: Cardiology is characterized by its state-of-the-art biomedical
      technology and the predominance of Evidence-Based Medicine. This predominance
      makes it difficult for healthcare professionals to deal with the ethical dilemmas
      that emerge in this subspecialty. This paper is a first endeavor to empirically
      investigate the axiological foundations of the healthcare professionals in a
      cardiology hospital. Our pilot study selected, as the target population,
      cardiology personnel not only because of their difficult ethical deliberations
      but also because of the stringent conditions in which they have to make them.
      Therefore, there is an urgent need to reconsider clinical ethics and Value-Based
      Medicine. This study proposes a qualitative analysis of the values and the
      virtues of healthcare professionals in a cardiology hospital in order to
      establish how the former impact upon the medical and ethical decisions made by
      the latter. RESULTS: We point out the need for strengthening the roles of
      healthcare personnel as educators and guidance counselors in order to meet the
      ends of medicine, as well as the need for an ethical discernment that is
      compatible with our results, namely, that the ethical values developed by
      healthcare professionals stem from their life history as well as their
      professional education. CONCLUSION: We establish the kind of actions,
      communication skills and empathy that are required to build a stronger patient
      healthcare professional relationship, which at the same time improves prognosis,
      treatment efficiency and therapeutic adhesion.

PMID- 23531272
TI  - Does the perception of neighborhood built environmental attributes influence
      active transport in adolescents?
AB  - BACKGROUND: Among Belgian adolescents active transport (AT) is a common physical
      activity (PA) behavior. Preliminary evidence suggests that AT can be an important
      opportunity for increasing adolescents' daily PA levels. To inform interventions,
      predictors of this PA behavior need to be further explored. Therefore, in the
      perspective of the ecological models this study aimed (a) to investigate the
      relationship between the perception of neighborhood built environmental
      attributes and adolescents' AT and (b) to explore the contribution of the
      perception of neighborhood built environmental attributes beyond psychosocial
      factors. METHODS: For the purpose of this study, data from the Belgian
      Environmental Physical Activity Study in Youth (BEPAS-Y), performed between 2008
      and 2009, was used. The final study population consisted of 637 adolescents aged
      13-15 years. The participants completed a survey measuring demographic and
      psychosocial factors, the Flemish Physical Activity Questionnaire and the Dutch
      version of the Neighborhood Environmental Walkability Scale. RESULTS: A set of
      stepwise linear regression analyses with backward elimination revealed that a
      shorter distance to school, perceiving neighborhoods to have connected streets, a
      lower degree of land use mix diversity, less infrastructure for walking and a
      lower quality of the infrastructure for walking are associated with more min/day
      AT to and from school (p all <0.05). Furthermore, marginally significant
      associations (p < 0.10) were found between residential density and safety from
      crime and AT to and from school. No relationship between the perception of the
      neighborhood built environmental attributes and walking for transport during
      leisure time and cycling for transport during leisure time was found.
      CONCLUSIONS: The substantial contribution of the perception of neighbourhood
      built environmental attributes to AT found in Belgian adults, could not totally
      be confirmed by this study for Belgian adolescents. Among Belgian adolescents,
      the contribution of neighborhood environmental perceptions to explain the
      variance in AT seems to be dependent of the purpose of AT. Further research is
      needed to explore this relationship in specific subgroups and to overcome some of
      the limitations this study had to contend with.

PMID- 23531273
TI  - Overweight and obesity among African immigrants in Oslo.
AB  - BACKGROUND: Norway is experiencing an increase in overweight/obese adults, with
      immigrants from developing countries carrying a heavy burden. The aim of this
      study is to assess the prevalence of overweight and obesity among Somali
      immigrants in Oslo. FINDINGS: A cross-sectional study involving 208 respondents
      aged 25 and over was conducted among Somali immigrants in Oslo, using a
      structured questionnaire. Prevalence of overweight/obesity varied by gender, with
      women having a significantly higher prevalence (66%) than men (28%). The mean BMI
      for females and males were 27.4 and 23.6, respectively. Similarly, 53% of women
      and 28% of men were abdominally obese. In a logistic regression analysis, both
      generalized and abdominal obesity were significantly associated with increasing
      duration of residence in Norway, and with being less physically active.
      CONCLUSION: Public health policymakers should facilitate an environment that
      enables Somali immigrants, particularly women, to lead healthy lifestyles. In
      this time of epidemiological transition, health education in the areas of
      physical exercise and healthy eating should be a major focus for working with new
      immigrants.

PMID- 23531274
TI  - Rumination and symptom reports in children and adolescents: results of a cross
      sectional and experimental study.
AB  - This study explores the relationship between a ruminative response style and
      symptom reports in children and adolescents of grades 5, 7 and 9 from German
      secondary schools. Questionnaires were used to assess rumination and symptom
      reports. A group of children and adolescents (N = 140) were asked to think first
      about the items before responding to them (increased attention condition), while
      a second group (N = 260) served as control group (standard condition). The
      assumption was that rumination and also additional attention to the symptoms by
      instruction would increase the reported frequency of experiencing somatic and
      psychological symptoms. The results showed significant relations between symptom
      reports and rumination, which increased with grade. There were sex differences
      for somatic symptom reports with increased symptom frequencies in girls, which
      were mediated by rumination. Moreover, instructing participants to think first
      about the items led to an increase in reported symptoms. It is concluded that an
      increased attention to symptoms of distress increases symptom reports, which may
      be induced momentarily by instruction and also more generally by a ruminative
      response style. Conclusions regarding prevention and concerning instructions in
      symptom report questionnaires are outlined. 

PMID- 23531275
TI  - Determinants at the N- and C-termini of Galpha12 required for activation of Rho
      mediated signaling.
AB  - BACKGROUND: Heterotrimeric guanine nucleotide binding proteins of the G12/13
      subfamily, which includes the alpha-subunits Galpha12 and Galpha13, stimulate the
      monomeric G protein RhoA through interaction with a distinct subset of Rho
      specific guanine nucleotide exchange factors (RhoGEFs). The structural features
      that mediate interaction between Galpha13 and RhoGEFs have been examined in
      crystallographic studies of the purified complex, whereas a Galpha12:RhoGEF
      complex has not been reported. Several signaling responses and effector
      interactions appear unique to Galpha12 or Galpha13, despite their similarity in
      amino acid sequence. METHODS: To comprehensively examine Galpha12 for regions
      involved in RhoGEF interaction, we screened a panel of Galpha12 cassette
      substitution mutants for binding to leukemia-associated RhoGEF (LARG) and for
      activation of serum response element mediated transcription. RESULTS: We
      identified several cassette substitutions that disrupt Galpha12 binding to LARG
      and the related p115RhoGEF. These Galpha12 mutants also were impaired in
      activating serum response element mediated signaling, a Rho-dependent response.
      Most of these mutants matched corresponding regions of Galpha13 reported to
      contact p115RhoGEF, but unexpectedly, several RhoGEF-uncoupling mutations were
      found within the N- and C-terminal regions of Galpha12. Trypsin protection assays
      revealed several mutants in these regions as retaining conformational activation.
      In addition, charge substitutions near the Galpha12 N-terminus selectively
      disrupted binding to LARG but not p115RhoGEF. CONCLUSIONS: Several structural
      aspects of the Galpha12:RhoGEF interface differ from the reported Galpha13:RhoGEF
      complex, particularly determinants within the C-terminal alpha5 helix and
      structurally uncharacterized N-terminus of Galpha12. Furthermore, key residues at
      the Galpha12 N-terminus may confer selectivity for LARG as a downstream effector.

PMID- 23531276
TI  - Nursing and midwifery regulation and HIV scale-up: establishing a baseline in
      East, Central and Southern Africa.
AB  - INTRODUCTION: Shifting HIV treatment tasks from physicians to nurses and midwives
      is essential to scaling-up HIV services in sub-Saharan Africa. Updating nursing
      and midwifery regulations to include task shifting and pre-service education
      reform can help facilitate reaching new HIV targets. Donor-supported initiatives
      to update nursing and midwifery regulations are increasing. However, there are
      gaps in our knowledge of current practice and education regulations and a lack of
      information to target and implement regulation strengthening efforts. We
      conducted a survey of national nursing and midwifery councils to describe current
      nursing and midwifery regulations in 13 African countries. METHODS: A 30-item
      survey was administered to a convenience sample of 13 national nursing and
      midwifery regulatory body leaders in attendance at the PEPFAR-supported African
      Health Profession Regulatory Collaborative meeting in Nairobi, Kenya on 28
      February, 2011. The survey contained questions on task shifting and regulations
      such as registration, licensure, scope of practice, pre-service education
      accreditation, continuing professional development and use of international
      guidelines. Survey data were analyzed to present country-level, comparative and
      regional findings. RESULTS: Task shifting to nurses and midwives was reported in
      11 of the 13 countries. Eight countries updated their scope of practice within
      the last five years; only one reported their regulations to reflect task
      shifting. Countries vary with regard to licensure, pre-service accreditation and
      continuing professional development regulations in place. There was no
      consistency in terms of what standards were used to design national practice and
      education regulations. DISCUSSION: Many opportunities exist to assist countries
      to modernise regulations to incorporate important advancements from task shifting
      and pre-service reform. Appropriate, revised regulations can help sustain
      successful health workforce strategies and contribute to further scale-up HIV
      services and other global health priorities. CONCLUSIONS: This study provides
      fundamental information from which to articulate goals and to measure the impact
      of regulation strengthening efforts.

PMID- 23531277
TI  - Hydrothermal synthesis, crystal structure, and catalytic potential of a one
      dimensional molybdenum oxide/bipyridinedicarboxylate hybrid.
AB  - The reaction of MoO3, 2,2'-bipyridine-5,5-dicarboxylic acid (H2bpdc), water, and
      dimethylformamide in the mole ratio 1:1:1730:130 at 150  degrees C for 3 days in
      a rotating Teflon-lined digestion bomb leads to the isolation of the molybdenum
      oxide/bipyridinedicarboxylate hybrid material (DMA)[MoO3(Hbpdc)].nH2O (1) (DMA =
      dimethylammonium). Compound 1 was characterized by scanning electron microscopy,
      FT-IR and (13)C{(1)H} CP MAS NMR spectroscopies, and elemental and
      thermogravimetric analyses. The solid state structure of 1 was solved and refined
      through Rietveld analysis of high resolution synchrotron X-ray powder diffraction
      data in conjunction with information derived from the above techniques. The
      material, crystallizing in the noncentrosymmetric monoclinic space group Pc, is
      composed of an anionic one-dimensional organic-inorganic hybrid polymer,
      infinity(1)[MoO3(Hbpdc)](-), formed by corner-sharing distorted {MoO4N2}
      octahedra, which cocrystallizes with charge-balancing DMA(+) cations and one
      water molecule per metal center. In the crystal structure of 1, the close packing
      of individual anionic polymers, DMA(+) cations, and water molecules is mediated
      by a series of supramolecular contacts, namely strong (O-H...O, N(+)-H...O(-))
      and weak (C-H...O) hydrogen bonding interactions, and pi-pi contacts involving
      adjacent coordinated Hbpdc(-) ligands. The catalytic potential of 1 was
      investigated in the epoxidation reactions of the bioderived olefins methyl oleate
      (Ole) and DL-limonene (Lim) using tert-butylhydroperoxide (TBHP) as the oxygen
      donor and 1,2-dichloroethane (DCE) or (trifluoromethyl)benzene (BTF) as
      cosolvent, at 55 or 75  degrees C. Under these conditions, 1 acts as a source of
      active soluble species, leading to epoxide yields of up to 98% for methyl 9,10
      epoxystearate (BTF, 75  degrees C, 100% conversion of Ole) and 89% for 1,2-epoxy
      p-menth-8-ene (DCE, 55  degrees C, 95% conversion of Lim). Catalytic systems
      employing the ionic liquid 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide as solvent could be effectively recycled.

PMID- 23531278
TI  - Recombinant factor VIIa for uncontrollable bleeding in patients with
      extracorporeal membrane oxygenation: report on 15 cases and literature review.
AB  - INTRODUCTION: Bleeding is the most frequent complication in patients receiving
      venoarterial or venovenous extracorporeal membrane oxygenation (ECMO).
      Recombinant activated factor VII (rFVIIa) has been used in these patients with
      conflicting results. We describe our experience with rFVIIa for refractory
      bleeding in this setting and review the cases reported in the literature.
      METHODS: Clinical characteristics, demographics, bleeding, thrombotic
      complications, mortality, and rFVIIa administration were retrospectively
      collected for analysis from the electronic charts of the 15 patients in our
      intensive care unit who received rFVIIa while being given ECMO from January 2006
      to March 2011. RESULTS: Fifteen patients received rFVIIa for persistent bleeding
      under venoarterial (n=11) or venovenous (n=4) ECMO. Bleeding dramatically
      decreased in 14 patients, without a major thrombotic event, except in one patient
      in whom a major stroke could not be ruled out. Two circuits were changed within
      the 48 hours after rFVIIa administration for clots in the membrane and decreased
      oxygenation but without massive clotting. The mortality rate was 60%.
      CONCLUSIONS: rFVIIa use for intractable hemorrhaging in patients receiving ECMO
      controlled bleeding, without major thrombotic events, and with 60% dying. Hence,
      its use warrants discussion, and clinicians should be aware of the possibility of
      potentially life-threatening systemic thrombosis, emboli, or circuit clotting.
      Whether rFVIIa can save the lives of such patients remains to be determined.

PMID- 23531279
TI  - Caloric restriction favorably impacts metabolic and immune/inflammatory profiles
      in obese mice but curcumin/piperine consumption adds no further benefit.
AB  - BACKGROUND: Obesity is associated with low-grade inflammation and impaired immune
      response. Caloric restriction (CR) has been shown to inhibit inflammatory
      response and enhance cell-mediated immune function. Curcumin, the bioactive
      phenolic component of turmeric spice, is proposed to have anti-obesity and anti
      inflammation properties while piperine, another bioactive phenolic compound
      present in pepper spice, can enhance the bioavailability and efficacy of
      curcumin. This study sought to determine if curcumin could potentiate CR's
      beneficial effect on immune and inflammatory responses in obesity developed in
      mice by feeding high-fat diet (HFD). METHODS: Mice were fed a HFD for 22 wk and
      then randomized into 5 groups: one group remained on HFD ad libitum and the
      remaining 4 groups were fed a 10% CR (reduced intake of HFD by 10% but
      maintaining the same levels of micronutrients) in the presence or absence of
      curcumin and/or piperine for 5 wk, after which CR was increased to 20% for an
      additional 33 wk. At the end of the study, mice were sacrificed, and spleen cells
      were isolated. Cells were stimulated with T cell mitogens, anti-CD3/CD28
      antibodies, or lipopolysaccharide to determine T cell proliferation, cytokine
      production, and CD4+ T cell subpopulations. RESULTS: Compared to HFD control
      group, all CR mice, regardless of the presence of curcumin and/or piperine, had
      lower body weight and fat mass, lower levels of blood glucose and insulin, and
      fewer total spleen cells but a higher percentage of CD4+ T cells. Additionally,
      they demonstrated lower production of pro-inflammatory cytokines IL-1beta and TNF
      alpha, a trend toward lower IL-6, and lower production of PGE2, a lipid molecule
      with pro-inflammatory and T cell-suppressive properties. Mice with CR alone had
      higher splenocyte proliferation and IL-2 production, but this effect of CR was
      diminished by spice supplementation. CR alone or in combination with spice
      supplementation had no effect on production of cytokines IL-4, IL-10, IFN-gamma,
      and IL-17, or the proportion of different CD4+ T cell subsets. CONCLUSION: CR on
      an HFD favorably impacts both metabolic and immune/inflammatory profiles;
      however, the presence of curcumin and/or piperine does not amplify CR's
      beneficial effects.

PMID- 23531280
TI  - Impact of treatment planning target volumen (PTV) size on radiation induced
      diarrhoea following selenium supplementation in gynecologic radiation oncology--a
      subgroup analysis of a multicenter, phase III trial.
AB  - BACKGROUND: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828
      835,2010), we assessed whether an adjuvant supplementation with selenium (Se)
      improves Se status and reduces the radiation-induced side-effects of patients
      treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a
      potential relation between the planning target volume (PTV) of the RT and the Se
      effect concerning radiation induced diarrhoea was evaluated in detail. METHODS:
      Whole blood Se concentrations had been measured in patients with cervical (n=11)
      and uterine cancer (n=70) after surgical treatment, during, and at the end of RT.
      Patients with initial Se concentrations of less than 84 MUg/l were categorized as
      Se-deficient and randomized before RT to receive Se (as sodium selenite) per os
      on the days of RT, or to receive no supplement during RT. Diarrhoea was graded
      according to the Common Toxicity Criteria system (CTC, Version 2a). The
      evaluation of the PTV of the RT was ascertained with the help of a specialised
      computer-assisted treatment planning software used for radiation planning
      procedure. RESULTS: A total of 81 patients had been randomized for the initial
      supplementation study, 39 of which received Se [selenium group, SeG] and 42
      serving as controls [control group, CG]. Mean Se levels did not differ between
      SeG and CG upon study initiation, but were significantly higher in the SeG
      compared to the CG at the end of RT. The actuarial incidence of at least CTC 2
      radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG
      (p=0.04). The median PTV in both groups was 1302 ml (916-4608). With a PTV of <=
      1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was
      22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50).
      In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least
      CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19
      patients) in the CG (p=0.046). CONCLUSIONS: Se supplementation during RT was
      effective to improve blood Se status in Se-deficient cervical and uterine cancer
      patients, and reduces episodes and severity of RT-induced diarrhoea. This effect
      was most pronounced and significant in patients with large PTV (> 1302 ml).

PMID- 23531281
TI  - Comparison of whole blood and PBMC assays for T-cell functional analysis.
AB  - BACKGROUND: Tuberculosis remains the foremost cause of morbidity and mortality,
      more than any other single infectious disease in the world. Cell mediated immune
      response plays a crucial role in the control of tuberculosis. Therefore,
      measuring cell mediated immune response against the antigens is having a vital
      role in understanding the pathogenesis of tuberculosis, which will also help in
      the diagnosis of and vaccination for tuberculosis. FINDINGS: The aim of the
      present study was to compare and optimize the assay conditions to measure the
      cell mediated immune response against M. tuberculosis specific antigens. Because
      the conventional PBMC assays (due to requirement of large volume of blood sample)
      are unable to screen more number of antigens within the same blood sample. So,
      here we have compared 6 days culture supernatants of 1:5 and 1:10 diluted blood
      and PBMCs from healthy laboratory volunteers, to assess the proliferative
      response of T lymphocytes and secreted IFN-gamma levels against purified
      recombinant antigen of M. tuberculosis (MPT51, Rv3803c), crude antigens of M.
      tuberculosis (PPD) and mitogen (PHA). CONCLUSIONS: We have observed good
      correlation between each assay and also the mean difference of these assays did
      not reach the statistical significance (p>0.05). From these results, we conclude
      that 1:10 diluted whole-blood cultures can be well-suited as an alternative assay
      to measure cytokine production and lymphocyte proliferation in comparison to the
      conventional PBMC assays. Moreover, 1:10 diluted blood assays require less volume
      of blood when compared to PBMC assays which will be useful particularly in
      paediatric and field studies in endemic countries, where blood volume is a
      limiting factor.

PMID- 23531284
TI  - [In Process Citation].

PMID- 23531282
TI  - Children's physical activity and parents' perception of the neighborhood
      environment: neighborhood impact on kids study.
AB  - BACKGROUND: Physical activity is important to children's physical health and well
      being. Many factors contribute to children's physical activity, and the built
      environment has garnered considerable interest recently, as many young children
      spend much of their time in and around their immediate neighborhood. Few studies
      have identified correlates of children's activity in specific locations. This
      study examined associations between parent report of their home neighborhood
      environment and children's overall and location-specific physical activity.
      METHODS: Parents and children ages 6 to 11 (n=724), living in neighborhoods
      identified through objective built environment factors as high or low in physical
      activity environments, were recruited from Seattle and San Diego metropolitan
      areas, 2007-2009. Parents completed a survey about their child's activity and
      perceptions of home neighborhood environmental attributes. Children wore an
      accelerometer for 7 days. Multivariate regression models explored perceived
      environment correlates of parent-reported child's recreational physical activity
      in their neighborhood, in parks, and in general, as well as accelerometry-based
      moderate-to-vigorous activity (MVPA) minutes. RESULTS: Parent-reported proximity
      to play areas correlated positively with both accelerometery MVPA and parent
      reported total child physical activity. Lower street connectivity and higher
      neighborhood aesthetics correlated with higher reported child activity in the
      neighborhood, while reported safety from crime and walk and cycle facilities
      correlated positively with reported child activity in public recreation spaces.
      CONCLUSIONS: Different aspects of parent's perceptions of the neighborhood
      environment appear to correlate with different aspects of children's activity.
      However, prioritizing closer proximity to safe play areas may best improve
      children's physical activity and, in turn, reduce their risk of obesity and
      associated chronic diseases.

PMID- 23531285
TI  - [In Process Citation].

PMID- 23531283
TI  - MutComFocal: an integrative approach to identifying recurrent and focal genomic
      alterations in tumor samples.
AB  - BACKGROUND: Most tumors are the result of accumulated genomic alterations in
      somatic cells. The emerging spectrum of alterations in tumors is complex and the
      identification of relevant genes and pathways remains a challenge. Furthermore,
      key cancer genes are usually found amplified or deleted in chromosomal regions
      containing many other genes. Point mutations, on the other hand, provide
      exquisite information about amino acid changes that could be implicated in the
      oncogenic process. Current large-scale genomic projects provide high throughput
      genomic data in a large number of well-characterized tumor samples. METHODS: We
      define a Bayesian approach designed to identify candidate cancer genes by
      integrating copy number and point mutation information. Our method exploits the
      concept that small and recurrent alterations in tumors are more informative in
      the search for cancer genes. Thus, the algorithm (Mutations with Common Focal
      Alterations, or MutComFocal) seeks focal copy number alterations and recurrent
      point mutations within high throughput data from large panels of tumor samples.
      RESULTS: We apply MutComFocal to Diffuse Large B-cell Lymphoma (DLBCL) data from
      four different high throughput studies, totaling 78 samples assessed for copy
      number alterations by single nucleotide polymorphism (SNP) array analysis and 65
      samples assayed for protein changing point mutations by whole exome/whole
      transcriptome sequencing. In addition to recapitulating known alterations,
      MutComFocal identifies ARID1B, ROBO2 and MRS1 as candidate tumor suppressors and
      KLHL6, IL31 and LRP1 as putative oncogenes in DLBCL. CONCLUSIONS: We present a
      Bayesian approach for the identification of candidate cancer genes by integrating
      data collected in large number of cancer patients, across different studies. When
      trained on a well-studied dataset, MutComFocal is able to identify most of the
      reported characterized alterations. The application of MutComFocal to large-scale
      cancer data provides the opportunity to pinpoint the key functional genomic
      alterations in tumors.

PMID- 23531286
TI  - [Point of view regarding early treatment. Interview with Jean-Baptiste Kerbrat].

PMID- 23531287
TI  - [Point of view regarding early treatment. Interview with Marie-Josephe Deshayes
      and Emmanuelle Jaunet].

PMID- 23531288
TI  - [Reversible damages: loss of chance].
AB  - Chance is the probability that a particular event may or may not occur and, in
      this sense, a loss of chance** can be defined as the missed opportunities
      resulting from the loss of the possibility that a favorable event will occur (a
      contrario, the failure to take risks)***. This is a self-imposed liability that
      should be distinguished from the final damage. Moral damage is a notion that is
      very close to loss of chance although it is based on indemnification from the
      final damage of an affliction or malady.

PMID- 23531289
TI  - [For early treatment of Class II div 1 malocclusions].
AB  - Should treatment of a Class II div. 1 malocclusion begin in the early, in mixed
      dentition or later in the adolescent dentition? In a Cochrane review, the authors
      conclude: "The evidence suggests that providing early orthodontic treatment for
      children with prominent upper front teeth is no more effective than providing one
      course of orthodontic treatment when the child is in early adolescence." So,
      should you wait to treat ? Certainly not ! Many arguments in favor of early
      treatment are: reduction of the risk of fracture of prominent incisors, esthetic
      factors, increase in patient self-esteem and reduction of negative social
      experiences, reduction of the length of fixed appliance therapy thereby reducing
      possible iatrogenic effects, creating an environment more favorable to harmonious
      growth and development, without forgetting the legal concept of loss of
      opportunity. These elements will be developed in a literature review and
      illustrated by a clinical case.

PMID- 23531290
TI  - [Early treatment for class III malocclusions: the facts].
AB  - The goal of this article is to present some evidence based facts in order to
      answer the following questions: 1) Is early treatment of class III malocclusions
      effective? 2) Which therapeutic device is the most effective? 3) Are the results
      lasting? The positions of Jean Delaire and the author regarding the usefulness of
      routine early treatment for these dysmorphia will be discussed in a second
      article [4].

PMID- 23531291
TI  - [Early treatment of class III malocclusions: conventional wisdom].
AB  - After a first article [5] written to present the published evidence based facts
      concerning early treatment of class III malocclusions, the authors present, in
      this second article, their reasons why they think our routine early treatment of
      these dysmorphia is useful. When orthodontists clearly present all the elements
      involved in this therapeutic choice to patients and their parents, they usually
      decide on early treatment. A clear time frame and simple therapeutic procedures
      that young patients accept easily, makes it possible to achieve significantly
      good results. This approach requires the cooperation of the children and their
      parents and beyond the orthodontic sphere, of pediatricians and
      otolaryngologists. They will use three clinical cases to illustrate the
      therapeutic concepts that support their opinions.

PMID- 23531292
TI  - [Very early treatment, early treatment or just watchful waiting? Thoughts based
      on the follow-up treatment of class III with vertical excess].
AB  - The debate concerning the optimal timing for beginning treatment of maxillo
      facial dysmorphia is far from over. The possible choices are very early treatment
      in the primary dentition, early treatment only during a period of time when the
      mixed dentition is stable or waiting until complete adult dentition is present,
      at the end of, or close to the end of, the growth period. Opting for early
      treatment is problematic because it is difficult to make a very early diagnosis
      (and sometimes impossible to make when there are no strong developmental signs
      for dysmorphia present), long-term prognosis can always be inaccurate, patients
      may not yet be psychologically mature enough, there is insufficient anchorage
      available, ultimately a two-stage treatment is required and hence a longer
      process, the feeling that this is "experimental therapy", that, in case of
      failure, leads to disappointment and a loss of confidence. Opting for later
      treatment reassures both orthodontist and patient; however, these delayed
      treatments might represent a lost opportunity for some patients who must a priori
      undergo more extractions and additional surgical procedures. The presentation of
      a case of hyperdivergent class III occlusion, where the orthodontist hesitates to
      treat at various stages of growth, and finally ends up performing a late surgical
      treatment, illustrates quite well the problem we face in choosing a timeframe for
      treatment.

PMID- 23531293
TI  - [Course of action in front of children or adolescent suffering from
      temporomandibular disorders].
AB  - Temporomandibular disorders are described in children from the age of 4. Their
      prevalence and severity increase strongly during the second decade, which
      corresponds to the period of orthodontic treatments. At this age the most common
      symptoms are joint clicking sounds (more than 70% of the cases), sometimes
      accompanied by episodes of intermittent locking. They would be favored by oral
      parafunctional activities (gum chewing, biting habits, bruxism...), ligamentous
      hyperlaxity and modification of the intra-articular space relations during
      growth. The questioning of the patient and his parents and clinical examination
      (muscular, articular and occlusal) are essential and very often sufficient for
      establishing the diagnosis. Even more than in the adult, the therapeutic attitude
      must rely on conservative and non-irreversible methods (explanations, suppression
      of the parafunctions, occlusal splints in the case of severe bruxism). These
      considerations are illustrated by the presentation of two representative clinical
      cases of temporomandibular disorders frequently encountered in children and
      adolescents.

PMID- 23531294
TI  - [A Study of the relationship between craniofacial morphology and the occlusion in
      lacteal dentition: occipital remodeling specificities and basicranial individual
      features that play an occlusal key role].
AB  - Before performing any procedure or initiating early intervention on children in
      lacteal dentition, it is crucial to closely investigate a few key elements of the
      cranial base of the child. A first step of diagnostics is needed - the
      classification of the dysharmony ie its squelettal and/or functional element -
      before we prescribe a major orthopedic treatment or just stop dysfunctions using
      simple functional appliances. To confront these constraints of diagnostic, a set
      of 243 children in the lacteal dentition was examined. Our clinical expertise
      made it possible to select cephalometric measurements that would be supposedly
      linked with the type of skeletal dysharmony (based on cranial and facial osseous
      landmarks located on the profile-view of a digital tele-X-ray). The occlusal
      classification takes into account occlusal criteria and the design of the
      masticatory function. Statistical analysis (namely linear discriminant analysis
      of cephalometric variables) indicates that in lacteal dentition, some cranial
      architectural features have preferred links with specific occlusions. We noticed
      that the amplitude of basicranial "flexure" (hence the sphenoidal angle) is
      influenced by the occipital remodeling: the ontogenic process of flexion of the
      base and the amplitude of closure of the sphenoid angle are under controlled by
      the remodeling of the occipital bone in three main modalities. Correlations exist
      between these groups and the facial equilibrium, like a forward or backward
      position of the chin. The important clinical deduction is that the masticatory
      function in lacteal dentition is organized by architectural constraints that
      arise from the remodeling of the cranial base; the squelettal effect of
      dysfunctions is certainly specific to each type of dysfunction, nonetheless it
      also depends on the architectural uniqueness of the cranial base.

PMID- 23531296
TI  - [In Process Citation].

PMID- 23531295
TI  - [Success rate and efficiency of activator treatment].
AB  - In a retrospective multicentre study, the success rate and efficiency of
      activator treatment were analysed. All patients from two University clinics
      (Giessen, Germany and Berne, Switzerland) that fulfilled the selection criteria
      (Class II division 1 malocclusion, activator treatment, no aplasia, no extraction
      of permanent teeth, no syndromes, no previous orthodontic treatment except
      transverse maxillary expansion, full available records) were included in the
      study. The subject material amounted to 222 patients with a mean age of 10.6
      years. Patient records, lateral head films, and dental casts were evaluated.
      Treatment was classified as successful if the molar relationship improved by at
      least half to three-fourths cusp width depending on whether or not the leeway
      space was used during treatment. Group comparisons were carried out using
      Wilcoxon two-sample and Kruskal-Wallis tests. For discrete data, chi-square
      analysis was used and Fisher's exact test when the sample size was small.
      Stepwise logistic regression was also employed. The success rate was 64 per cent
      in Giessen and 66 per cent in Berne. The only factor that significantly (P!0:001)
      influenced treatment success was the level of co-operation. In approximately 27
      per cent of the patients at both centres, the post-treatment occlusion was an
      ideal Class I. In an additional 38 per cent of the patients, marked improvements
      in occlusal relationships were found. In subjects with Class II division 1
      malocclusions, in which orthodontic treatment is performed by means of
      activators, a marked improvement of the Class II dental arch relationships can be
      expected in approximately 65% of subjects. Activator treatment is more efficient
      in the late than in the early mixed dentition.

PMID- 23531297
TI  - [In Process Citation].

PMID- 23531298
TI  - Pulmonary surfactant is indispensable in order to simulate the in vivo situation.
AB  - The article of Gasser et al. [Part Fibre Toxicol. 24; 9:17, 2012] describes the
      interaction of carbon nanotubes with cells within a complex cell culture model.
      Besides various toxicity parameters, the influence of coating with pulmonary
      surfactant was investigated. Pulmonary surfactant covers the entire alveolar
      region with the main function of decreasing the surface tension in the alveoli to
      prevent alveolar collapse. Although each inhaled nanoparticle, reaching the
      alveoli, will come into contact with pulmonary surfactant which will probably
      lead to a surfactant coating, pulmonary surfactant components are not commonly
      integrated in in vitro systems. Gasser and co-workers have shown that this
      surfactant coating is able to influence the further interaction with cellular
      systems. Hence, each scientist, working with in vitro systems and nanoparticles,
      should think of integrating pulmonary surfactant structures in order to harmonize
      the in vitro systems with the in vivo situation. In the present commentary we
      discuss the most important points of the manuscript of Gasser et al. and discuss
      where the usage of pulmonary surfactant can be further optimized.

PMID- 23531299
TI  - Diagnostic accuracy of early urinary index changes in differentiating transient
      from persistent acute kidney injury in critically ill patients: multicenter
      cohort study.
AB  - INTRODUCTION: Urinary indices have limited effectiveness in separating transient
      acute kidney injury (AKI) from persistent AKI in ICU patients. Their time-course
      may vary with the mechanism of AKI. The primary objective of this study was to
      evaluate the diagnostic value of changes over time of the usual urinary indices
      in separating transient AKI from persistent AKI. METHODS: An observational
      prospective multicenter study was performed in six ICUs involving 244 consecutive
      patients, including 97 without AKI, 54 with transient AKI, and 93 with persistent
      AKI. Urinary sodium, urea and creatinine were measured at ICU admission (H0) and
      on 6-hour urine samples during the first 24 ICU hours (H6, H12, H18, and H24).
      Transient AKI was defined as AKI with a cause for renal hypoperfusion and
      reversal within 3 days. RESULTS: Significant increases from H0 to H24 were noted
      in fractional excretion of urea (median, 31% (22 to 41%) and 39% (29 to 48%) at
      H24, P<0.0001), urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40),
      P<0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57
      (29 to 104), P=0.01). Fractional excretion of sodium did not change significantly
      during the first 24 hours in the ICU (P=0.13). Neither urinary index values at
      ICU admission nor changes in urinary indices between H0 and H24 performed
      sufficiently well to recommend their use in clinical setting (area under the
      receiver-operating characteristic curve<=0.65). CONCLUSION: Although urinary
      indices at H24 performed slightly better than those at H0 in differentiating
      transient AKI from persistent AKI, they remain insufficiently reliable to be
      clinically relevant.

PMID- 23531300
TI  - Isolation, characterization, and nuclease activity of biologically relevant
      chromium(V) complexes with monosaccharides and model diols. Likely intermediates
      in chromium-induced cancers.
AB  - The stabilization of Cr(V) by biological 1,2-diolato ligands, including
      carbohydrates, glycoproteins, and sialic acid derivatives, is likely to play a
      crucial role in the genotoxicity of Cr(VI) and has also been implicated in the
      antidiabetic effect of Cr(III). Previously, such complexes have been observed by
      electron paramagnetic resonance (EPR) spectroscopy in living cells or animals,
      treated with carcinogenic Cr(VI), as well as in numerous model systems, but
      attempts to isolate them have been elusive. Recently, the first crystal structure
      of a Cr(V) complex with cis-1,2-cyclohexanediol (1, a close structural analogue
      of carbohydrates) has been reported. In this work, Cr(V) complexes of the general
      formula [Cr(V)OL2](-) [where LH2 = 1, cis-1,2-cyclopentanediol (2), D-glucose
      (3), D-mannose (4), D-galactose (5), and D-ribose (6)] have been isolated from
      light-catalyzed reactions of Cr(VI) (anhydrous Na2Cr2O7) with slight molar
      excesses of the corresponding ligands in N,N-dimethylformamide. The complexes
      were characterized by elemental analyses, electrospray mass spectrometry (ESMS),
      and EPR spectroscopy. Studies by electronic absorption spectroscopy have shown
      that the solids isolated from reactions of Cr(VI) with 3-6 contained mixtures of
      Cr(V) complexes (40-65 mol %) and Cr(III) species (probably complexes with
      oxidized ligands), while those from reactions with 1 and 2 were practically pure
      Cr(V). The first isolation of solids containing significant proportions of
      chromium(V) monosaccharide complexes led to the definitive assignment of their
      general formula ([Cr(V)OL2](-), based on ESMS), in agreement with the earlier EPR
      spectroscopic data. The first direct comparison of the decomposition rates of
      Cr(V) complexes with 1-6, made possible by isolation of the solids, have shown
      that the complexes with five-membered-ring ligands (2 and 6) are more stable at
      pH ~ 7 compared with their six-membered-ring counterparts (1 and 3-5). This
      finding emphasizes the likely biological roles of chromium(V) pentose complexes,
      e.g., those with sugar residues of RNA, ATP, or NAD(P)H. Finally, the first
      direct evidence for the ability of these Cr(V) complexes to cause oxidative DNA
      damage in the absence of added reductants or oxidants has been obtained. These
      data support significant roles for chromium(V) 1,2-diolato complexes in the
      diverse biological activities of Cr(VI) and Cr(III).

PMID- 23531301
TI  - Evaluation and comparison of New 4DCT based strategies for proton treatment
      planning for lung tumors.
AB  - PURPOSE: To evaluate different strategies for proton lung treatment planning
      based on four-dimensional CT (4DCT) scans. METHODS AND MATERIALS: Twelve cases,
      involving only gross tumor volumes (GTV), were evaluated. Single image sets of
      (1) maximum intensity projection (MIP3) of end inhale (EI), middle exhale (ME)
      and end exhale (EE) images; (2) average intensity projection (AVG) of all phase
      images; and (3) EE images from 4DCT scans were selected as primary images for
      proton treatment planning. Internal target volumes (ITVs) outlined by a clinician
      were imported into MIP3, AVG, and EE images as planning targets. Initially,
      treatment uncertainties were not included in planning. Each plan was imported
      into phase images of 4DCT scans. Relative volumes of GTVs covered by 95% of
      prescribed dose and mean ipsilateral lung dose of a phase image obtained by
      averaging the dose in inspiration and expiration phases were used to evaluate the
      quality of a plan for a particular case. For comparing different planning
      strategies, the mean of the averaged relative volumes of GTVs covered by 95% of
      prescribed dose and its standard deviation for each planning strategy for all
      cases were used. Then, treatment uncertainties were included in planning. Each
      plan was recalculated in phase images of 4DCT scans. Same strategies were used
      for plan evaluation except dose-volume histograms of the planning target volumes
      (PTVs) instead of GTVs were used and the mean and standard deviation of the
      relative volumes of PTVs covered by 95% of prescribed dose and the ipsilateral
      lung dose were used to compare different planning strategies. RESULTS: MIP3 plans
      without treatment uncertainties yielded 96.7% of the mean relative GTV covered by
      95% of prescribed dose (standard deviations of 5.7% for all cases). With
      treatment uncertainties, MIP3 plans yielded 99.5% of mean relative PTV covered by
      95% of prescribed dose (standard deviations of 0.7%). Inclusion of treatment
      uncertainties improved PTV dose coverage but also increased the ipsilateral mean
      lung dose in general, and reduced the variations of the PTV dose coverage among
      different cases. Plans based on conventional axial CT scan (CVCT) gave the
      poorest PTV dose coverage (about 96% of mean relative PTV covered by 95% isodose)
      compared to MIP3 and EE plans, which resulted in 100% of PTV covered by 95%
      isodose for tumors with relatively large motion. AVG plans demonstrated PTV dose
      coverage of 89.8% and 94.4% for cases with small tumors. MIP3 plans demonstrated
      superior tumor coverage and were least sensitive to tumor size and tumor
      location. CONCLUSION: MIP3 plans based on 4DCT scans were the best planning
      strategy for proton lung treatment planning.

PMID- 23531302
TI  - Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice.
AB  - BACKGROUND: Mesenchymal stem cell (MSC) transplantation has emerged as a
      promising therapy for liver fibrosis. Issues concerning poor MSC survival and
      engraftment in the fibrotic liver still persist and warrant development of a
      strategy to increase MSC potency for liver repair. The present study was designed
      to examine a synergistic role for Interleukin-6 (IL-6) and MSCs therapy in the
      recovery of carbon tetrachloride (CCl(4)) induced injured hepatocytes in vitro
      and in vivo. METHODS: Injury was induced through 3 mM and 5 mM CCl(4) treatment
      of cultured hepatocytes while fibrotic mouse model was established by injecting
      0.5 ml/kg CCl(4) followed by treatment with IL-6 and MSCs. Effect of MSCs and IL
      6 treatment on injured hepatocytes was determined by lactate dehydrogenase
      release, RT-PCR for (Bax, Bcl-xl, Caspase3, Cytokeratin 8, NFkappaB, TNF-alpha)
      and annexin V apoptotic detection. Analysis of MSC and IL-6 treatment on liver
      fibrosis was measured by histopathology, PAS, TUNEL and Sirius red staining, RT
      PCR, and liver function tests for Bilirubin and Alkaline Phosphatase (ALP).
      RESULTS: A significant reduction in LDH release and apoptosis was observed in
      hepatocytes treated with a combination of MSCs and IL-6 concomitant with
      upregulation of anti-apoptotic gene Bcl-xl expression and down regulation of bax,
      caspase3, NFkappaB and TNF-alpha. Adoptive transfer of MSCs in fibrotic liver
      pretreated with IL-6 resulted increased MSCs homing and reduced fibrosis and
      apoptosis. Hepatic functional assessment demonstrated reduced serum levels of
      Bilirubin and ALP. CONCLUSION: Pretreatment of fibrotic liver with IL-6 improves
      hepatic microenvironment and primes it for MSC transplantation leading to
      enhanced reduction of liver injury after fibrosis. Synergistic effect of IL-6 and
      MSCs seems a favored therapeutic option in attenuation of liver apoptosis and
      fibrosis accompanied by improved liver function.

PMID- 23531303
TI  - AMBIENT: Active Modules for Bipartite Networks--using high-throughput
      transcriptomic data to dissect metabolic response.
AB  - BACKGROUND: With the continued proliferation of high-throughput biological
      experiments, there is a pressing need for tools to integrate the data produced in
      ways that produce biologically meaningful conclusions. Many microarray studies
      have analysed transcriptomic data from a pathway perspective, for instance by
      testing for KEGG pathway enrichment in sets of upregulated genes. However, the
      increasing availability of species-specific metabolic models provides the
      opportunity to analyse these data in a more objective, system-wide manner.
      RESULTS: Here we introduce ambient (Active Modules for Bipartite Networks), a
      simulated annealing approach to the discovery of metabolic subnetworks (modules)
      that are significantly affected by a given genetic or environmental change. The
      metabolic modules returned by ambient are connected parts of the bipartite
      network that change coherently between conditions, providing a more detailed view
      of metabolic changes than standard approaches based on pathway enrichment.
      CONCLUSIONS: ambient is an effective and flexible tool for the analysis of high
      throughput data in a metabolic context. The same approach can be applied to any
      system in which reactions (or metabolites) can be assigned a score based on some
      biological observation, without the limitation of predefined pathways. A Python
      implementation of ambient is available at
      http://www.theosysbio.bio.ic.ac.uk/ambient.

PMID- 23531305
TI  - Bridging collaboration to innovation.

PMID- 23531304
TI  - Estimation of total phenol and in vitro antioxidant activity of Albizia procera
      leaves.
AB  - BACKGROUND: Research on natural products has gained a wide popularity due to the
      potential of discovering active compounds. The antioxidant properties contained
      in plants have been proposed as one of the mechanisms for the observed beneficial
      effect. Therefore, the present study investigated the antioxidant activity and
      total phenolic contents of various solvent extracts of Albizia procera leaves.
      METHODS: Antioxidant activity of the methanol extract and its derived fractions
      petroleum ether (APP), carbon tetrachloride (APC), dichloromethane (APD), ethyl
      acetate (APE), and residual aqueous fraction (APA) of the leaves of Albizia
      procera was performed by in vitro chemical analyses. Total phenolic content of
      the APM and other five fractions were also determined. APM and its derived
      fractions were also subjected to preliminary phytochemical screening test for
      various constituents. RESULTS: Phytochemical screening revealed the presence of
      saponins, steroids, tannins, glycosides and flavonoids in the extracts. Amongst
      the extracts, APE showed the highest total phenolic content (449.18 +/- 18.41mg
      of gallic acid equivalent/g of extract). In DPPH (1,1-diphenyl-2-picrylhydrazyl)
      radical scavenging test, the IC(50) value of APM, APP, APC, APD, APE and APA was
      43.43, 63.60, 166.18, 41.15, 11.79, and 63.06 MUg/mL, respectively. Therefore,
      among the APM and its derived fractions, APE showed the highest antioxidant
      activity which is comparable to that of standard ascorbic acid (AA) (IC(50) 10.12
      MUg/mL). The total antioxidant capacity was found to be varied in different
      fractions. The reducing activity on ferrous ion was ranked as APE > APD > APM >
      APA > APC. CONCLUSION: The above evidences suggest that APE of A. procera leaf is
      a potential source of natural antioxidant and can be used to prevent diseases
      associated with free radicals.

PMID- 23531306
TI  - Connections: mind, health, spirit.

PMID- 23531307
TI  - Priority patient safety issues identified by perioperative nurses.
AB  - Much of the work done by perioperative nurses focuses on patient safety.
      Perioperative nurses are aware that unreported near misses occur every day, and
      they use that knowledge to prioritize activities to protect the patient. The
      purpose of this study was to identify the highest priority patient safety issues
      reported by perioperative RNs. We sent a link to an anonymous electronic survey
      to all AORN members who had e-mail addresses in AORN's member database. The
      survey asked respondents to identify top perioperative patient safety issues. We
      received 3,137 usable responses and identified the 10 highest priority safety
      issues, including wrong site/procedure/patient surgery, retained surgical items,
      medication errors, failures in instrument reprocessing, pressure injuries,
      specimen management errors, surgical fires, perioperative hypothermia, burns from
      energy devices, and difficult intubation/airway emergencies. Differences were
      found among practice settings. The information from this study can be used to
      inform the development of educational programs and the allocation of resources to
      enhance safe perioperative patient care.

PMID- 23531308
TI  - Using simulation training to improve perioperative patient safety.
AB  - Simulation learning provides medical and nursing personnel with the opportunity
      to develop and refine their skills without putting patients at risk. Faced with
      ensuring the competence of a large number of new staff members, the management
      team at one facility implemented a simulation training program. Surgical team
      members are able to participate in an ongoing program of simulated scenarios
      involving surgical drape fires and airway fires, cardiac arrest of patients in
      the supine position and prone position, respiratory depression in the
      postanesthesia care unit, and malignant hyperthermia. The simulations help OR
      staff members identify problems that can happen during real emergencies and help
      them work as a team to prepare for events that may represent life-threatening
      situations for patients.

PMID- 23531309
TI  - Instituting code blue drills in the OR.
AB  - A code blue in the OR is a low-volume, high-risk event. To be effective during a
      code blue event, perioperative personnel must be able to properly execute a
      response plan and perform seldom-used skills and procedures. I developed and
      implemented a code blue drill educational experience for OR staff members that
      included a review of code blue policy, how to use a defibrillator, and simulated
      code blue scenarios. In addition, I worked with educational facilitators to
      provide an assessment of the personnel who performed the simulated code blue
      drills to identify key learning opportunities, such as gaps in communication,
      poor performance of cardiopulmonary resuscitation, ineffective delegation skills,
      and lack of assertiveness. One month after the educational experience, all team
      members passed an observed competency for responding to a code blue in a
      simulation laboratory. These results show the effectiveness of the educational
      experience as part of the code blue drills program in the hospital's main OR.

PMID- 23531310
TI  - What's new in the transplant OR?
AB  - Advancements in transplantation offer promising treatment options for a variety
      of diseases. Organ donation, an essential part of organ transplantation, may be
      performed at hospitals even if the facility is not a transplant center;
      therefore, perioperative nurses should be aware of developments in
      transplantation and the implications for patient care at their facilities.
      Considerations for organ transplant protocols include the type of documentation
      required, the elements of the transplant OR time out, and the use of
      intraoperative anti-rejection medications. Considerations for organ donation
      protocols include issues specific to a deceased donor, a living donor, or a
      donation after cardiac death. Newer developments in the transplant OR include
      laparoscopic kidney donation and transplantation, kidney paired donation
      transplantation, other living donor procedures, and transplantation procedures
      using robotic technology.

PMID- 23531311
TI  - A quality improvement project for safe and effective patient positioning during
      robot-assisted surgery.
AB  - During the initiation of a new robotic surgery program, a quality improvement
      team explored different techniques for positioning patients in the lithotomy and
      steep Trendelenburg position during robot-assisted procedures. Concerns
      associated with placing patients in the steep Trendelenburg position include the
      patient slipping toward the head of the bed and experiencing hemodynamic changes
      that may result in a rise in blood pressure, increased intraocular and
      intracranial pressures, and difficulty with ventilation, particularly in patients
      with a high body mass index. Skin integrity is also of concern because
      perioperative personnel are responsible for protecting the patient's skin from
      excessive sheer, friction, and injury. The quality improvement team evaluated and
      compared two positioning devices: an air-inflated positioning device and high
      density foam padding. Both methods allowed personnel to position the patient
      without compromise; the surgeons performing the robot-assisted procedures
      preferred the high-density foam padding.

PMID- 23531312
TI  - Proper use of surgical n95 respirators and surgical masks in the OR.
AB  - Proper adherence to infection control precautions, including appropriate
      selection and use of personal protective equipment (PPE), is of significant
      importance to the health and well-being of perioperative personnel. Surgical
      masks are intended for use as a barrier to protect the wearer's face from large
      droplets and splashes of blood and other body fluids; however, surgical and high
      filtration surgical laser masks do not provide enough protection to be considered
      respiratory PPE. Potential exposure to airborne contaminants and infectious
      agents, including those present in surgical smoke, necessitates the use of
      respiratory PPE, such as a surgical N95 particulate filtering facepiece
      respirator. Filtering facepiece respirators greatly reduce a wide size range of
      particles from entering the wearer's breathing zone and are designed to protect
      the user from both droplet and airborne particles. Every health care worker who
      must use a respirator to control hazardous exposures in the workplace must be
      trained to properly use the respirator and pass a fit test before using it in the
      workplace.

PMID- 23531313
TI  - Learning to adapt during a surgical mission to remote Africa.

PMID- 23531314
TI  - Surgical attire compliance for safe patients and practitioners.

PMID- 23531316
TI  - Medication reconciliation pitfalls.

PMID- 23531317
TI  - A randomized cross-over study of inhalation of diesel exhaust, hematological
      indices, and endothelial markers in humans.
AB  - BACKGROUND: Exposure to traffic-related air pollution (TRAP) is considered a
      trigger for acute cardiovascular events. Diesel Exhaust (DE) is a major
      contributor to TRAP in the world. We evaluated the effect of DE inhalation on
      circulating blood cell populations, hematological indices, and systemic
      inflammatory cytokines in humans using a specialized facility. METHODS: In a
      randomized double-blind crossover study balanced to order, 17 metabolic syndrome
      (MetS) and 15 healthy subjects inhaled filtered air (FA) or DE exposure in two
      hour sessions on different days with a minimum 2-week washout period. We
      collected blood pre-exposure, 7, and 22 hours after exposure initiation and
      measured the complete blood count and differential. We performed multiplex
      cytokine assay to measure the changes in the systemic inflammatory cytokines, and
      endothelial adhesion molecules (n=15). A paired analysis compared the effect of
      DE and FA exposures for the change from pre-exposure to the subsequent time
      points. RESULTS: A significant increase in the hematocrit was noted 7 hrs after
      DE [1.4% (95% CI: 0.9 to 1.9%)] compared to FA exposure [0.5% (95% CI: -0.09 to
      1.0%); p=0.008. The hemoglobin levels increased non-significantly at 7 hrs post
      DE [0.3 gm/dL (95% CI: 0.2 to 0.5 gm/dL)] versus FA exposure [0.2 gm/dL (95% CI:
      0 to 0.3 gm/dL)]; p=0.06. Furthermore, the platelet count increased 22 hrs after
      DE exposure in healthy, but not in MetS subjects [DE: 16.6 (95% CI: 10.2 to 23)
      thousand platelets/mL versus [FA: 3.4 (95% CI: -9.5 to 16.3) thousand
      platelets/mL)]; p=0.04. No DE effect was observed for WBC, neutrophils,
      lymphocytes or erythrocytes. Using the multiplex assay, small borderline
      significant increases in matrix metalloproteinase-9, interleukins (IL)-1 beta, 6
      and 10 occurred 7 hrs post exposure initiation, whereas E-selectin, intercellular
      adhesion molecule-1, and vascular cell adhesion molecule -1, and myeloperoxidase
      22 hrs post exposure. CONCLUSIONS: Our results suggest that short-term DE
      exposure results in hemoconcentration and thrombocytosis, which are important
      determinants of acute cardiovascular events. Multiplex assay showed a non
      significant increase in IL-1beta and IL-6 immediately post exposure followed by
      myeloperoxidase and endothelial activation molecules. Further specific assays in
      a larger population will improve our understanding of the systemic inflammatory
      mechanisms following acute exposure to TRAP.

PMID- 23531318
TI  - Dopexamine can attenuate the inflammatory response and protect against organ
      injury in the absence of significant effects on hemodynamics or regional
      microvascular flow.
AB  - INTRODUCTION: The effects of dopexamine, a beta2-agonist, on perioperative and
      sepsis-related hemodynamic, microvascular, immune, and organ dysfunction are
      controversial and poorly understood. We investigated these effects in a rodent
      model of laparotomy and endotoxemia. METHODS: In two experiments, 80 male Wistar
      rats underwent laparotomy. In 64 rats, this was followed by administration of
      endotoxin; the remainder (16) underwent sham endotoxemia. Endotoxemic animals
      received either dopexamine at 0.5, 1, or 2 MUg/kg/min or 0.9% saline vehicle
      (controls) as resuscitation fluid. The effects of dopexamine on global
      hemodynamics, mesenteric regional microvascular flow, renal and hepatic function
      and immune activation were evaluated. RESULTS: Endotoxin administration was
      associated with a systemic inflammatory response (increased plasma levels of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10, as
      well as cell-adhesion molecules CD11a and CD11b), and increased pulmonary
      myeloperoxidase (MPO) activity (indicating pulmonary leukocyte infiltration),
      whereas biochemical changes demonstrated lactic acidosis with significant renal
      and hepatic injury. Dopexamine administration was associated with less-severe
      lactic acidosis (pooled dopexamine versus controls, (lactate, 2.2 mM+/-0.2 mM
      versus 4.0 mM+/-0.5 mM; P<0.001) and reductions in the systemic inflammatory
      response (pooled dopexamine versus control, 4 hour (TNF-alpha): 324 pg/ml+/-93
      pg/ml versus 97 pg/ml+/-14 pg/ml, p<0.01), pulmonary myeloperoxidase (MPO)
      activity, and hepatic and renal injury (pooled dopexamine versus control (ALT):
      81 IU/L+/-4 IU/L versus 138 IU/L+/-25 IU/L; P<0.05; (creatinine): 49.4 MUM+/-3.9
      MUM versus 76.2 MUM+/-9.8 MUM; P<0.005). However, in this study, clinically
      relevant doses of dopexamine were not associated with clinically significant
      changes in MAP, CI, or gut regional microvascular flow. CONCLUSIONS: In this
      model, dopexamine can attenuate the systemic inflammatory response, reduce tissue
      leukocyte infiltration, and protect against organ injury at doses that do not
      alter global hemodynamics or regional microvascular flow. These findings suggest
      that immunomodulatory effects of catecholamines may be clinically significant
      when used in critically ill surgical patients and are independent of their
      hemodynamic actions.

PMID- 23531319
TI  - A study of 131iodine-labeling of histamine-indomethacin: its in vivo therapeutic
      effect and anti-tumor mechanisms in Lewis-bearing lung cancer.
AB  - BACKGROUND: In our research,we study the effect of 131iodine-labeled histamine
      indomethacin (131I-His-IN). We focus on its in vivo therapeutic effect and anti
      tumor mechanisms in Lewis-bearing lung cancer. METHODS: 131I-His-IN was
      administered by garage to the mice. At different timepoints, we made
      autoradiography (ARG) slices to observe the distribution of 131I-His-IN in the
      cellular, and the sliced samples underwent hematoxylin and eosin (HE) staining
      for observation of tumor necrosis. Before treatment, the groups of mice underwent
      18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography
      (PET-CT) scans ,and they were then given physiologic saline, iodine 131 (131I),
      indomethacin (IN), Histamine-indomethacin (His-IN), and 131I-His-IN,
      respectively, three times daily for seven days. Seven days later, all the mice
      underwent 18F-FDG PET-CT scans again. We calculated the maximum standard uptake
      value (SUVmax) of the region of interest (ROI) and tumor inhibition rate at the
      same time. RESULTS: In ARG groups, black silver particle was concentrated in the
      nucleus and cytoplasm. 131I-His-IN mainly concentrated in tumor tissues. At 8
      hours after 131I-His-IN, the radioactivity uptake in tumor tissue was higher than
      in other organs (F=3.46, P<0.05). For the 18F-FDG PET-CT imaging, the tumor
      tissuses SUVmax of the ROI was lower compared to other groups after the treatment
      with 131I-His-IN. The tumor inhibitory rate (54.8%) in 131I-His-IN group was
      higher than in other groups, too. In the 131I-His-IN group the vascular
      endothelial growth factor (VEGF) decreased gradually compared to other groups.
      The tumor tissue necrotized obviously in 131I-His-IN group. CONCLUSIONS: Through
      these animal experiments, we found 131I-His-IN could inhibit the Lewis lung
      cancer cells. 131I-His-IN focused at the cell nucleus and cytoplasm. It could
      reduce VEGF and increase tumor inhibitory rate. At the same time, 18F-FDG PET-CT
      scan could be used for a curative effect and monitoring of disease prognosis.

PMID- 23531320
TI  - Growth inhibition of different human colorectal cancer xenografts after a single
      intravenous injection of oncolytic vaccinia virus GLV-1h68.
AB  - BACKGROUND: Despite availability of efficient treatment regimens for early stage
      colorectal cancer, treatment regimens for late stage colorectal cancer are
      generally not effective and thus need improvement. Oncolytic virotherapy using
      replication-competent vaccinia virus (VACV) strains is a promising new strategy
      for therapy of a variety of human cancers. METHODS: Oncolytic efficacy of
      replication-competent vaccinia virus GLV-1h68 was analyzed in both, cell cultures
      and subcutaneous xenograft tumor models. RESULTS: In this study we demonstrated
      for the first time that the replication-competent recombinant VACV GLV-1h68
      efficiently infected, replicated in, and subsequently lysed various human
      colorectal cancer lines (Colo 205, HCT-15, HCT-116, HT-29, and SW-620) derived
      from patients at all four stages of disease. Additionally, in tumor xenograft
      models in athymic nude mice, a single injection of intravenously administered GLV
      1h68 significantly inhibited tumor growth of two different human colorectal cell
      line tumors (Duke's type A-stage HCT-116 and Duke's type C-stage SW-620),
      significantly improving survival compared to untreated mice. Expression of the
      viral marker gene ruc-gfp allowed for real-time analysis of the virus infection
      in cell cultures and in mice. GLV-1h68 treatment was well-tolerated in all
      animals and viral replication was confined to the tumor. GLV-1h68 treatment
      elicited a significant up-regulation of murine immune-related antigens like IFN
      gamma, IP-10, MCP-1, MCP-3, MCP-5, RANTES and TNF-gamma and a greater
      infiltration of macrophages and NK cells in tumors as compared to untreated
      controls. CONCLUSION: The anti-tumor activity observed against colorectal cancer
      cells in these studies was a result of direct viral oncolysis by GLV-1h68 and
      inflammation-mediated innate immune responses. The therapeutic effects occurred
      in tumors regardless of the stage of disease from which the cells were derived.
      Thus, the recombinant vaccinia virus GLV-1h68 has the potential to treat
      colorectal cancers independently of the stage of progression.

PMID- 23531321
TI  - The last generation of bacterial growth in limiting nutrient.
AB  - BACKGROUND: Bacterial growth as a function of nutrients has been studied for
      decades, but is still not fully understood. In particular, the growth laws under
      dynamically changing environments have been difficult to explore, because of the
      rapidly changing conditions. Here, we address this challenge by means of a
      robotic assay and measure bacterial growth rate, promoter activity and substrate
      level at high temporal resolution across the entire growth curve in batch
      culture. As a model system, we study E. coli growing under nitrogen or carbon
      limitation, and explore the dynamics in the last generation of growth where
      nutrient levels can drop rapidly. RESULTS: We find that growth stops abruptly
      under limiting nitrogen or carbon, but slows gradually when nutrients are not
      limiting. By measuring growth rate at a 3 min time resolution, and inferring the
      instantaneous substrate level, s, we find that the reduction in growth rate MU
      under nutrient limitation follows Monod's law, MU=MU0(s/(k(s)+s)). By following
      promoter activity of different genes we found that the abrupt stop of growth
      under nitrogen or carbon limitation is accompanied by a pulse-like up-regulation
      of the expression of genes in the relevant nutrient assimilation pathways. We
      further find that sharp stop of growth is conditional on the presence of
      regulatory proteins in the assimilation pathway. CONCLUSIONS: The observed sharp
      stop of growth accompanied by a pulsed expression of assimilation genes allows
      bacteria to compensate for the drop in nutrients, suggesting a strategy used by
      the cells to prolong exponential growth under limiting substrate.

PMID- 23531322
TI  - Efficacy of selamectin, spinosad, and spinosad/milbemycin oxime against the KS1
      Ctenocephalides felis flea strain infesting dogs.
AB  - BACKGROUND: A study was conducted to evaluate and compare the efficacy of
      selamectin, spinosad, and spinosad/milbemycin oxime against the KS1 strain of
      Ctenocephalides felis on dogs. METHODS: Forty-eight dogs were selected for the
      study and two batches of 24 were blocked and allocated randomly to treatment
      groups and flea count times. There were four treatment groups of 12 dogs each:
      negative control, topical selamectin, oral spinosad/milbemycin oxime, and oral
      spinosad. Each dog was infested with 100 fleas on Days -2, 7, 14, 21 and 28.
      Within each treatment group, six dogs were flea counted at 24 hours and six at 48
      hours after treatment or post-infestation. On Day 0, dogs received a single
      treatment of the appropriate drug according to the approved commercial label.
      RESULTS: Efficacy of selamectin against an existing flea infestation was 60.4%
      and 91.4% at 24 and 48 hours, respectively, whereas spinosad/milbemycin oxime and
      spinosad were 100% at both time points. All products were >90% effective within
      24 hours after subsequent infestations on Days 7, 14 and 21. Following the Day 28
      flea infestation, selamectin was 93% and 95.7% effective at 24 and 48 hours,
      respectively. Whereas the efficacy of spinosad/milbemycin oxime following the day
      28 infestation was 84.7% and 87.5% at 24 and 48 hours, respectively and spinosad
      alone was 72.9% and 76.3% effective at 24 and 48 hours, respectively.
      CONCLUSIONS: After initial application, the two oral spinosad products had a more
      rapid onset of flea kill than topical selamectin which took up to 48 hours to
      control (>90%) the existing infestation. However, for subsequent weekly flea
      infestations selamectin had similar or better efficacy than spinosad or
      spinosad/milbemycin oxime at 24 and 48 hours after infestation.
      Spinosad/milbemycin oxime and spinosad were >90% effective against the KS1 strain
      from Day 1 to Day 23. Whereas, selamectin was >90% effective against the KS1
      strain of C. felis from Day 2 to Day 30.

PMID- 23531323
TI  - Ken Donaldson: retirement of a young mind.

PMID- 23531325
TI  - Paclitaxel and cisplatin combined with intensity-modulated radiotherapy for upper
      esophageal carcinoma.
AB  - PURPOSE: This study was conducted to evaluate the effectiveness and safety of
      intensity-modulated radiotherapy (IMRT) and concurrent paclitaxel plus cisplatin
      (TP regimen) for upper esophageal carcinoma. METHODS: 36 patients of upper
      esophageal carcinoma were retrospectively analyzed. Patients were treated with
      IMRT (median 60 Gy) combined with concurrent TP regimen chemotherapy. The Kaplan
      Meier analysis was performed in statistical analysis. Toxicities were recorded
      according to the NCI CTC version 3.0. RESULTS: 36 patients aged 43-73 years
      (median 57 years). The median follow-up period was 14.0 months. The 1-year and 2
      year survival rates were 83.3% and 42.8% respectively. The median progression
      free survival (PFS) time and overall survival (OS) time were 12.0 (95% CI: 7.8
      16.2 months) and 18.0 months (95% CI: 9.9-26.1 months), respectively. Grade 3
      neutropenia, radiation-induced esophagitis and radiodermatitis were observed in 5
      (13.9%), 3 (8.3%) and 8 (22.2%) patients respectively. There were two treatment
      related deaths due to esophageal perforation and hemorrhea. CONCLUSIONS: For
      those patients with upper esophageal carcinoma, IMRT combined with concurrent TP
      regimen chemotherapy was an effective treatment. However, more attention should
      be paid to the occurrence of perforation and hemorrhea.

PMID- 23531326
TI  - Optimizing the definition of intrauterine growth restriction: the multicenter
      prospective PORTO Study.
AB  - OBJECTIVE: The objective of the Prospective Observational Trial to Optimize
      Pediatric Health in Intrauterine Growth Restriction (IUGR) (PORTO Study), a
      national prospective observational multicenter study, was to evaluate which
      sonographic findings were associated with perinatal morbidity and mortality in
      pregnancies affected by growth restriction, originally defined as estimated fetal
      weight (EFW) <10th centile. STUDY DESIGN: Over 1100 consecutive ultrasound-dated
      singleton pregnancies with EFW <10th centile were recruited from January 2010
      through June 2012. A range of IUGR definitions were used, including EFW or
      abdominal circumference <10th, <5th, or <3rd centiles, with or without
      oligohydramnios and with or without abnormal umbilical arterial Doppler
      (pulsatility index >95th centile, absent or reversed end-diastolic flow). Adverse
      perinatal outcome, defined as a composite outcome of intraventricular hemorrhage,
      periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing
      enterocolitis, bronchopulmonary dysplasia, sepsis, and death was documented for
      all cases. RESULTS: Of 1116 fetuses, 312 (28%) were admitted to neonatal
      intensive care unit and 58 (5.2%) were affected by adverse perinatal outcome
      including 8 mortalities (0.7%). The presence of abnormal umbilical Doppler was
      significantly associated with adverse outcome, irrespective of EFW or abdominal
      circumference measurement. The only sonographic weight-related definition
      consistently associated with adverse outcome was EFW <3rd centile (P = .0131);
      all mortalities had EFW <3rd centile. Presence of oligohydramnios was clinically
      important when combined with EFW <3rd centile (P = .0066). CONCLUSION: Abnormal
      umbilical artery Doppler and EFW <3rd centile were strongly and most consistently
      associated with adverse perinatal outcome. Our data call into question the
      current definitions of IUGR used. Future studies may address whether using
      stricter IUGR cutoffs comparing various definitions and management strategies has
      implications on resource allocation and pregnancy outcome.

PMID- 23531327
TI  - Is thrombin activation predictive of subsequent preterm delivery?
AB  - OBJECTIVE: To determine the relation between thrombin generation (measured by
      thrombin-antithrombin [TAT] complexes) early in pregnancy and subsequent preterm
      delivery. STUDY DESIGN: Select cohort of 731 women undergoing indicated second
      trimester amniocentesis prospectively followed to delivery. Primary outcome was
      preterm delivery. TAT levels were examined continuously and categorized by
      quartiles. Multivariable techniques were applied to adjust for potential
      confounders. Receiver operating characteristic curve analysis was used to
      determine a discriminatory cutoff level for TAT complexes. RESULTS: TAT
      concentration was significantly higher in women who delivered preterm (median,
      98.9 mcg/L) than in those who did not (median, 66.3 mcg/L; P < .001). This
      difference persisted when 55 spontaneous preterm deliveries (median, 87.6 mcg/L)
      and 34 indicated preterm deliveries (median, 117.7 mcg/L) were separately
      compared with controls (P = .04 and P < .001, respectively). Crude and adjusted
      odds ratio for preterm delivery in the upper 2 TAT quartiles relative to the
      uppermost quartile relative to the lowest quartile were 2.45 (95% confidence
      interval [CI], 1.36-4.72; P = .004) and 2.31 (95% CI, 1.18-4.65; P = .017),
      respectively. Despite these distinct differences, the area under the receiver
      operating characteristic curve was only 0.62 (95% CI, 0.56-0.69), indicating poor
      performance of TAT concentration as a risk discriminator. CONCLUSION: Amniotic
      fluid levels of TAT complexes in the second trimester are elevated in women who
      subsequently deliver preterm, suggesting that thrombin generation may be involved
      in the various etiopathogenic mechanisms leading to preterm delivery.

PMID- 23531324
TI  - Quality of life and pruritus in patients with severe sepsis resuscitated with
      hydroxyethyl starch long-term follow-up of a randomised trial.
AB  - INTRODUCTION: The effects of hydroxyethyl starch (HES) on patient-centered
      outcome measures have not been fully described in patients with severe sepsis. We
      assessed health-related quality of life (HRQoL) and the occurrence of pruritus in
      patients with severe sepsis randomized to resuscitation with HES 130/0.42 or
      Ringer's acetate. METHODS: We did post hoc analyses of the Danish survivors
      (n=295) of the 6S trial using mailed questionnaires on self-perceived HRQoL
      (Short Form (SF) - 36) and pruritus. RESULTS: Median 14 months (interquartile
      range 10 to 18) after randomization, 182 (61%) and 185 (62%) completed
      questionnaires were obtained for the assessment of HRQoL and pruritus,
      respectively. Responders were older than nonresponders, but characteristics at
      randomization of the responders in the HES vs. Ringer's groups were comparable.
      At follow-up, the patients in the HES group had lower mental component summary
      scores than those in the Ringer's group (median 45 (interquartile range 36 to 55)
      vs. 53 (39 to 60), P=0.01). The group differences were mainly in the scales of
      vitality and mental health. There was no difference in the physical component
      summary scores between groups, but patients in the HES group scored worse in
      bodily pain. Forty-nine percent of patients allocated to HES had experienced
      pruritus at any time after ICU discharge compared to 43% of those allocated to
      Ringer's (relative risk 1.13, 95% confidence interval 0.83 to 1.55, P=0.43).
      CONCLUSIONS: At long-term follow-up patients with severe sepsis assigned to
      resuscitation with HES 130/0.42 had worse self-perceived HRQoL than those
      assigned to Ringer's acetate whereas there were no statistically significant
      differences in the occurrence of pruritus.

PMID- 23531328
TI  - The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized
      controlled trial.
AB  - OBJECTIVES: Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid
      (DHA), has been associated with perinatal depression, but there is evidence that
      supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA
      in treating depressive symptoms. This trial tested the relative effects of EPA-
      and DHA-rich fish oils on prevention of depressive symptoms among pregnant women
      at an increased risk of depression. STUDY DESIGN: We enrolled 126 pregnant women
      at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a
      history of depression) in early pregnancy and randomly assigned them to receive
      EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA
      plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression
      Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment,
      26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were
      analyzed at entry and at 34-36 weeks' gestation. RESULTS: One hundred eighteen
      women completed the trial. There were no differences between groups in BDI scores
      or other depression endpoints at any of the 3 time points after supplementation.
      The EPA- and DHA-rich fish oil groups exhibited significantly increased
      postsupplementation concentrations of serum EPA and serum DHA respectively. Serum
      DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late
      pregnancy. CONCLUSION: EPA-rich fish oil and DHA-rich fish oil supplementation
      did not prevent depressive symptoms during pregnancy or postpartum.

PMID- 23531330
TI  - Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced
      myocardial necrosis: a new therapeutic implication.
AB  - BACKGROUND: Ritonavir is a HIV protease inhibitor. In addition to its antiviral
      effect, Ritonavir directly inhibits the insulin-regulated glucose transporter
      GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of
      Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not
      investigated. In the present study, we evaluated the role of Ritonavir in
      isoproterenol-induced myocardial necrosis in vivo and compared the effect with
      Phlorizin, a nonslective SGLTs inhibitor. METHODS: Isoproterenol (ISO) (150
      mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause
      myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and
      Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two
      different groups of mice before isoproterenol administration. RESULTS AND
      DISCUSSION: Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days)
      administration caused significant (p < 0.05) increase in heart/body weight ratio,
      and myocardial necrosis as evident by significant (p < 0.05) increase in serum
      markers i.e. SGOT and CK; and cardiac histopathological changes. Significant (p <
      0.05) reduction in myocardial SOD and catalase activities, and GSH level along
      with a significant (p < 0.05) rise in myocardial TBARS and nitric oxide levels
      were observed after ISO administration. However, administration of phlorizin, a
      SGLT1 inhibitor has been found to exhibit partial protection in ISO induced
      myocardial necrosis, as observed by significant decrease in heart/body weight
      ratio and myocardial nitric oxide level; significant increase in myocardial SOD
      and catalase activities along with no histopathological alterations. On the other
      hand, administration of ritonavir, a nonspecific GLUT inhibitor has been found to
      exhibit complete protection as observed by normalisation of heart/body weight
      ratio, serum markers, antioxidant enzymes activities and histopathological
      alterations. In vitro study with heart homogenate confirmed no antioxidant effect
      of ritonavir and phlorizin in the absence and presence of isoproterenol.
      CONCLUSIONS: Our study concluded that ritonavir, a nonspecific GLUT inhibitors
      showed complete protection in catecholamine induced myocardial necrosis.

PMID- 23531331
TI  - Rwanda - lasting imprints of a genocide: trauma, mental health and psychosocial
      conditions in survivors, former prisoners and their children.
AB  - BACKGROUND: The 1994 genocide of the Tutsi in Rwanda left about one million
      people dead in a period of only three months. The present study aimed to examine
      the level of trauma exposure, psychopathology, and risk factors for posttraumatic
      stress disorder (PTSD) in survivors and former prisoners accused of participation
      in the genocide as well as in their respective descendants. METHODS: A community
      based survey was conducted in four sectors of the Muhanga district in the
      Southern Province of Rwanda from May to July 2010. Genocide survivors (n = 90),
      former prisoners (n = 83) and their respective descendants were interviewed by
      trained local psychologists. The PTSD Symptom Scale Interview (PSS-I) was used to
      assess PTSD, the Hopkins Symptom Checklist (HSCL-25) to assess symptoms of
      depression and anxiety and the relevant section of the M.I.N.I. to assess the
      risk for suicidality. RESULTS: Survivors reported that they had experienced on
      average twelve different traumatic event types in comparison to ten different
      types of traumatic stressors in the group of former prisoners. According to the
      PSS-I, the worst events reported by survivors were mainly linked to witnessing
      violence throughout the period of the genocide, whereas former prisoners
      emphasized being physically attacked, referring to their time spent in refugee
      camps or to their imprisonment. In the parent generation, when compared to former
      prisoners, survivors indicated being more affected by depressive symptoms (M =
      20.7 (SD = 7.8) versus M = 19.0 (SD = 6.4), U = 2993, p < .05) and anxiety
      symptoms (M = 17.2 (SD = 7.6) versus M = 15.4 (SD = 7.8), U = 2951, p < .05) but
      not with regard to the PTSD diagnosis (25% versus 22%, chi2(1,171) = .182, p =
      .669).A regression analysis of the data of the parent generation revealed that
      the exposure to traumatic stressors, the level of physical illness and the level
      of social integration were predictors for the symptom severity of PTSD, whereas
      economic status, age and gender were not. Descendants of genocide survivors
      presented with more symptoms than descendants of former prisoners with regard to
      all assessed mental disorders. CONCLUSIONS: Our study demonstrated particular
      long-term consequences of massive organized violence, such as war and genocide,
      on mental health and psychosocial conditions. Differences between families of
      survivors and families of former prisoners accused for participation in the
      Rwandan genocide are reflected in the mental health of the next generation.

PMID- 23531329
TI  - Developmental programming for allergy: a secondary analysis of the Mothers, Omega
      3, and Mental Health Study.
AB  - OBJECTIVE: Fetal dysregulation of T helper cell pathways may predispose to
      allergy, as high cord blood T helper 2/T helper 1 ratios have been shown to
      precede development of allergic diseases. We aimed to determine whether prenatal
      eicosapentaenoic acid and docosahexaenoic acid supplementation reduces T helper 2
      to T helper 1-associated chemokine ratios. We also explored the effect of mode of
      delivery on T helper 2/T helper 1 ratios. STUDY DESIGN: We conducted a secondary
      analysis of a randomized placebo controlled trial initially performed to assess
      the effects of docosahexaenoic acid or eicosapentaenoic acid supplementation on
      pregnancy-related depressive symptoms among 126 participants. Cord plasma
      specimens from 98 newborns were assayed for chemokines associated with T helper 2
      (thymus and activation-regulated chemokine [CCL17], macrophage-derived chemokine
      [CCL22], eotaxin [CCL 11]) and T helper 1 (interferon-inducible protein-10 [CXCL
      10]) by enzyme-linked immunosorbent assay and Multiplex immunoassays. Ratios of
      log-transformed chemokines macrophage-derived chemokine/interferon-inducible
      protein-10 and thymus and activation-regulated chemokine/interferon-inducible
      protein-10 were compared between groups by analyses of variance. Multiple linear
      regression was performed to examine associations between treatments and chemokine
      ratios, adjusting for covariates. RESULTS: After adjusting for gestational age at
      delivery, birthweight, and mode of delivery, both omega-3 supplementation groups
      were associated with lower macrophage-derived chemokine/interferon-inducible
      protein-10 ratios than placebo (eicosapentaenoic acid: coefficient -1.8; 95%
      confidence interval [CI], -3.6 to -0.05; P = .04; docosahexaenoic acid: -2.0; 95%
      CI, -3.9 to -0.07; P = .04). Similar associations were found for thymus and
      activation-regulated chemokine/interferon-inducible protein-10 (eicosapentaenoic
      acid: -1.5; 95% CI, -3.0 to 0.06; P = .06; docosahexaenoic acid -2.2; 95% CI, 
      3.8 to -0.52; P = .01). Cesarean delivery was associated with higher macrophage
      derived chemokine/interferon-inducible protein-10 (1.6; 95% CI, 0.01-3.3; P =
      .049) and thymus and activation-regulated chemokine/interferon-inducible protein
      10 (1.5; 95% CI, 0.1-2.9; P = .042) ratios than vaginal delivery. CONCLUSION:
      Prenatal supplementation with eicosapentaenoic acid and docosahexaenoic acid
      resulted in decreased cord blood T helper 2/T helper 1 chemokine ratios. Cesarean
      delivery was associated with a pronounced T helper 2 deviation at birth.

PMID- 23531332
TI  - Several benthic species can be used interchangeably in integrated sediment
      quality assessment.
AB  - The selection of the best management option for contaminated sediments requires
      the biological assessment of sediment quality using bioindicator organisms. There
      have been comparisons of the performance of different test species when exposed
      to naturally occurring sediments. However, more research is needed to determine
      their suitability to be used interchangeably. The sensitivity of two amphipod
      species (Ampelisca brevicornis and Corophium volutator) to sediments collected
      from four different commercial ports in Spain was tested. For comparison the
      lugworm, Arenicola marina, which is typically used for bioaccumulation testing,
      was also tested. Chemical analyses of the sediments were also conducted. All
      species responded consistently to the chemical exposure tests, although the
      amphipods, as expected, were more sensitive than the lugworm. It was found that
      C. volutator showed higher vulnerability than A.brevicornis. It was concluded
      that the three species can be used interchangeably in the battery of tests for
      integrated sediment quality assessment.

PMID- 23531333
TI  - Leukocyte capture and modulation of cell-mediated immunity during human sepsis:
      an ex vivo study.
AB  - INTRODUCTION: Promising preclinical results have been obtained with blood
      purification therapies as adjuvant treatment for sepsis. However, the mechanisms
      by which these therapies exert beneficial effects remain unclear. Some
      investigators have suggested that removal of activated leukocytes from the
      circulation might help ameliorate remote organ injury. We designed an
      extracorporeal hemoadsorption device capable of capturing both cytokines and
      leukocytes in order to test the hypothesis that leukocyte capture would alter
      circulating cytokine profiles and influence immunological cell-cell interactions
      in whole blood taken from patients with sepsis. METHODS: We performed a series of
      ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood
      circulated for four hours in closed loops with four specially designed
      miniaturized extracorporeal blood purification devices including two different
      hemoadsorption devices and a hemofilter in order to characterize leukocyte
      capture and to assess the effects of leukocyte removal on inflammation and immune
      function. RESULTS: Hemoadsorption was selective for removal of activated
      neutrophils and monocytes. Capture of these cells led to local release of certain
      cytokines, especially IL-8, and resulted in complex cell-cell interactions
      involved in cell-mediated immunity. Inhibition of cell adherence reversed the
      cytokine release and the effects on lymphocyte function. CONCLUSIONS: Monocyte
      and neutrophil capture using a sorbent polymer results in upregulation of IL-8
      and modulation of cell-mediated immunity. Further studies are needed to
      understand better these cellular interactions in order to help design better
      blood purification therapies.

PMID- 23531334
TI  - Comparative absorption, distribution, and excretion of titanium dioxide and zinc
      oxide nanoparticles after repeated oral administration.
AB  - BACKGROUND: The in vivo kinetics of nanoparticles is an essential to understand
      the hazard of nanoparticles. Here, the absorption, distribution, and excretion
      patterns of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles following
      oral administration were evaluated. METHODS: Nanoparticles were orally
      administered to rats for 13 weeks (7 days/week). Samples of blood, tissues
      (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy.
      The level of Ti or Zn in each sample was measured using inductively coupled
      plasma-mass spectrometry. RESULTS: TiO2 nanoparticles had extremely low
      absorption, while ZnO nanoparticles had higher absorption and a clear dose
      response curve. Tissue distribution data showed that TiO2 nanoparticles were not
      significantly increased in sampled organs, even in the group receiving the
      highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the
      liver and kidney were significantly increased compared with the vehicle control.
      ZnO nanoparticles in the spleen and brain were minimally increased. Ti
      concentrations were not significantly increased in the urine, while Zn levels
      were significantly increased in the urine, again with a clear dose-response
      curve. Very high concentrations of Ti were detected in the feces, while much less
      Zn was detected in the feces. CONCLUSIONS: Compared with TiO2 nanoparticles, ZnO
      nanoparticles demonstrated higher absorption and more extensive organ
      distribution when administered orally. The higher absorption of ZnO than TiO2
      nanoparticles might be due to the higher dissolution rate in acidic gastric
      fluid, although more thorough studies are needed.

PMID- 23531335
TI  - Lynch syndrome related endometrial cancer: clinical significance beyond the
      endometrium.
AB  - Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility
      syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused
      by a germline mutation in one of several DNA mismatch repair (MMR) genes. LS is
      the most common presentation of hereditary colorectal cancer (CRC), accounting
      for about 2-5% of all CRC cases. More recently, it is found that a similar number
      of endometrial cancers is also due to one of the MMR gene mutations. There has
      been significant progress in LS-related CRC in terms of molecular pathogenesis,
      risks, genetic basis, and cancer prevention. In contrast, the advance about LS
      related endometrial cancer (EC) is very much limited. In this commentary, we
      summarize the main clinicopathologic features of LS-related EC and propose
      universal screening for LS in individuals with endometrial cancer.

PMID- 23531336
TI  - Comparing the angiogenic potency of naive marrow stromal cells and Notch
      transfected marrow stromal cells.
AB  - BACKGROUND: Angiogenesis is a critical part of the endogenous repair process in
      brain injury and disease, and requires at least two sequential steps. First,
      angiogenic sprouting of endothelial cells occurs, which entails the initial
      proliferation of endothelial cells and remodeling of the surrounding
      extracellular matrix. Second, vessel stabilization is necessary to prevent
      vascular regression, which relies on vascular smooth muscle recruitment to
      surround the young vessels. Marrow stromal cells (MSCs) have been shown to
      promote revascularization after hindlimb ischemia, cardiac ischemia, and stroke.
      SB623 cells are derived from marrow stromal cells by transfection with a Notch1
      intracellular domain (NICD)-expressing plasmid and are known to elicit functional
      improvement in experimental stroke. These cells are currently used in human
      clinical testing for treatment of chronic stroke. In the current study, the
      angiogenic property of SB623 cells was investigated using cell-based assays.
      METHODS: Angiogenic paracrine factors secreted by SB623 cells and the parental
      MSCs were identified using the Qantibody Human Angiogenesis Array. To measure the
      angiogenic activity of conditioned medium from SB623 cells and MSCs, endothelial
      tube formation in the human umbilical vein endothelial cell (HUVEC) assay and
      endothelial cell sprouting and branching in the rodent aortic ring assay were
      quantified. To validate the angiogenic contribution of VEGF in conditioned
      medium, endothelial cells and aortic rings were treated with SU5416, which
      inhibits VEGFR2 at low dose. RESULTS: Conditioned medium from SB623 cells
      promoted survival and proliferation of endothelial cells under serum-deprived
      conditions and supports HUVEC vascular tube formation. In a rodent aortic ring
      assay, there was enhanced endothelial sprouting and branching in response to
      SB623-derived conditioned medium. SU5416 treatment partially reversed the effect
      of conditioned medium on endothelial cell survival and proliferation while
      completely abrogate HUVEC tube formation and endothelial cell sprouting and
      branching in aortic ring assays. CONCLUSIONS: These data indicate that SB623 cell
      secreted angiogenic factors promoted several aspects of angiogenesis, which
      likely contribute to promoting recovery in the injured brain.

PMID- 23531337
TI  - Sepsis biomarkers in unselected patients on admission to intensive or high
      dependency care.
AB  - INTRODUCTION: Although many sepsis biomarkers have shown promise in selected
      patient groups, only C-reactive protein and procalcitonin (PCT) have entered
      clinical practice. The aim of this study was to evaluate three promising novel
      sepsis biomarkers in unselected patients at admission to intensive care. We
      assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25)
      and heparin binding protein (HBP) in distinguishing patients with sepsis from
      those with a non-infective systemic inflammatory response and the ability of
      these markers to indicate severity of illness. METHODS: Plasma levels of the
      biomarkers, PCT and selected inflammatory cytokines were measured in samples
      taken from 219 patients during the first six hours of admission to intensive or
      high dependency care. Patients with a systemic inflammatory response were
      categorized as having sepsis or a non-infective aetiology, with or without
      markers of severity, using standard diagnostic criteria. RESULTS: Both PSP and
      sCD25 performed well as biomarkers of sepsis irrespective of severity of illness.
      For both markers the area under the receiver operating curve (AUC) was greater
      than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949).
      Procalcitonin and IL6 also performed well as markers of sepsis whilst in this
      intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901),
      IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and
      PCT reflected severity of illness and both markers performed well in
      differentiating patients with severe sepsis from severely ill patients with a non
      infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837
      (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with
      severity, the addition of sCD25 to either PCT or PSP in a multivariate model
      improved the diagnostic accuracy of either marker alone. CONCLUSIONS: PSP and
      sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the
      time of admission to intensive or high dependency care. These markers warrant
      further assessment of their prognostic value. Whereas previously published data
      indicate HBP has clinical utility in the emergency department, it did not perform
      well in an intensive-care population.

PMID- 23531338
TI  - Gene Ontology consistent protein function prediction: the FALCON algorithm
      applied to six eukaryotic genomes.
AB  - : Gene Ontology (GO) is a hierarchical vocabulary for the description of
      biological functions and locations, often employed by computational methods for
      protein function prediction. Due to the structure of GO, function predictions can
      be self- contradictory. For example, a protein may be predicted to belong to a
      detailed functional class, but not in a broader class that, due to the vocabulary
      structure, includes the predicted one.We present a novel discrete optimization
      algorithm called Functional Annotation with Labeling CONsistency (FALCON) that
      resolves such contradictions. The GO is modeled as a discrete Bayesian Network.
      For any given input of GO term membership probabilities, the algorithm returns
      the most probable GO term assignments that are in accordance with the Gene
      Ontology structure. The optimization is done using the Differential Evolution
      algorithm. Performance is evaluated on simulated and also real data from
      Arabidopsis thaliana showing improvement compared to related approaches. We
      finally applied the FALCON algorithm to obtain genome-wide function predictions
      for six eukaryotic species based on data provided by the CAFA (Critical
      Assessment of Function Annotation) project. 

PMID- 23531339
TI  - KRAS, BRAF, and TP53 deep sequencing for colorectal carcinoma patient
      diagnostics.
AB  - In colorectal carcinoma, KRAS (alias Ki-ras) and BRAF mutations have emerged as
      predictors of resistance to anti-epidermal growth factor receptor antibody
      treatment and worse patient outcome, respectively. In this study, we aimed to
      establish a high-throughput deep sequencing workflow according to 454
      pyrosequencing technology to cope with the increasing demand for sequence
      information at medical institutions. A cohort of 81 patients with known KRAS
      mutation status detected by Sanger sequencing was chosen for deep sequencing. The
      workflow allowed us to analyze seven amplicons (one BRAF, two KRAS, and four TP53
      exons) of nine patients in parallel in one deep sequencing run. Target
      amplification and variant calling showed reproducible results with input DNA
      derived from FFPE tissue that ranged from 0.4 to 50 ng with the use of different
      targets and multiplex identifiers. Equimolar pooling of each amplicon in a deep
      sequencing run was necessary to counterbalance differences in patient tissue
      quality. Five BRAF and 49 TP53 mutations with functional consequences were
      detected. The lowest mutation frequency detected in a patient tumor population
      was 5% in TP53 exon 5. This low-frequency mutation was successfully verified in a
      second PCR and deep sequencing run. In summary, our workflow allows us to process
      315 targets a week and provides the quality, flexibility, and speed needed to be
      integrated as standard procedure for mutational analysis in diagnostics.

PMID- 23531340
TI  - Synthesis of trace element bearing single crystals of Chlor-Apatite (Ca5(PO4)3Cl)
      using the flux growth method.
AB  - We present a new strategy on how to synthesize trace-element bearing (REE, Sr)
      chlorapatites Ca5(PO4)3Cl using the flux growth method. Synthetic apatites were
      up to several mm long, light blue in colour. The apatites were characterized
      using XRD, electron microprobe and laser ablation ICP-MS (LA-ICPMS) techniques
      and contained several hundred MUg/g La, Ce, Pr, Sm, Gd and Lu and about 1700
      MUg/g Sr. The analyses indicate that apatites were homogenous (within the
      uncertainties) for major and trace elements.

PMID- 23531341
TI  - Proteomic and functional annotation analysis of injured peripheral nerves reveals
      ApoE as a protein upregulated by injury that is modulated by metformin treatment.
AB  - BACKGROUND: Peripheral nerve injury (PNI) results in a fundamental reorganization
      of the translational machinery in the injured peripheral nerve such that protein
      synthesis is increased in a manner linked to enhanced mTOR and ERK activity. We
      have shown that metformin treatment, which activates adenosine monophosphate
      activated protein kinase (AMPK), reverses tactile allodynia and enhanced
      translation following PNI. To gain a better understanding of how PNI changes the
      proteome of the sciatic nerve and ascertain how metformin treatment may cause
      further change, we conducted a range of unbiased proteomic studies followed by
      biochemical experiments to confirm key results. RESULTS: We used multidimensional
      protein identification technology (MUDPIT) on sciatic nerve samples taken from
      rats with sham surgery, spinal nerve ligation (SNL) surgery or SNL + 200 mg/kg
      metformin treatment. MUDPIT analysis on these complex samples yielded a wide
      variety of proteins that were sorted according to their peptide counts in SNL and
      SNL + metformin compared to sham. These proteins were then submitted to
      functional annotation analysis to identify potential functional networks altered
      by SNL and SNL + metformin treatment. Additionally, we used click-chemistry-based
      labeling and purification of nascently synthesized proteins followed by MUDPIT to
      further identify peptides that were synthesized within the injured nerve. With
      these methods, we identified apolipoprotein E (ApoE) as a protein profoundly
      increased by PNI and further increased by PNI and metformin. This result was
      confirmed by Western Blot of samples from SNL rats and spared nerve injury (SNI)
      mice. Furthermore, we show that 7-day treatment with metformin in naive mice
      leads to an increase in ApoE expression in the sciatic nerve. CONCLUSIONS: These
      proteomic findings support the hypothesis that PNI leads to a fundamental
      reorganization of gene expression within the injured nerve. Our data identify a
      key association of ApoE with PNI that is regulated by metformin treatment. We
      conclude from the known functions of ApoE in the nervous system that ApoE may be
      an intrinsic factor linked to nerve regeneration after PNI, an effect that is
      further enhanced by metformin treatment.

PMID- 23531343
TI  - Special issue: Environmental influences and emerging mechanisms in the etiology
      of autism.

PMID- 23531342
TI  - Targeting p53 by small molecules in hematological malignancies.
AB  - p53 is a powerful tumor suppressor and is an attractive cancer therapeutic
      target. A breakthrough in cancer research came from the discovery of the drugs
      which are capable of reactivating p53 function. Most anti-cancer agents, from
      traditional chemo- and radiation therapies to more recently developed non-peptide
      small molecules exert their effects by enhancing the anti-proliferative
      activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can
      activate p53 have shown their anti-tumor effects in different types of
      hematological malignancies. Importantly, nutlin and PRIMA-1 have successfully
      reached the stage of phase I/II clinical trials in at least one type of
      hematological cancer. Thus, the pharmacological activation of p53 by these small
      molecules has a major clinical impact on prognostic use and targeted drug design.
      In the current review, we present the recent achievements in p53 research using
      small molecules in hematological malignancies. Anticancer activity of different
      classes of compounds targeting the p53 signaling pathway and their mechanism of
      action are discussed. In addition, we discuss how p53 tumor suppressor protein
      holds promise as a drug target for recent and future novel therapies in these
      diseases.

PMID- 23531344
TI  - Out-of-clinic patient communication in paediatric rheumatology: the extent and
      nature of demand.
AB  - BACKGROUND: Traditional funding models for public paediatric rheumatology care
      are typically based on providing medical services for a defined number of clinics
      per week. Anecdotally there is significant demand by patients and families for
      out-of-clinic communication with care providers and services provided under
      traditional funding models may not meet this need. Our aim was to determine the
      extent and nature of this 'hidden' demand in a tertiary paediatric rheumatology
      centre. METHODS: Communication data and diagnoses were extracted from the
      Rheumatology service database at our centre for the period 1/1/2009 to
      31/12/2011. Clinical activity data over the same time were obtained from hospital
      clinic databases. RESULTS: There were 5672 instances of communication with 749
      patients/families over 3 years, (mean 7.3/weekday). This increased over time in
      parallel with clinical activity. 41% of clinic patients sought communication with
      the team out of clinic hours. 58% were telephone calls, 36% emails and 6%
      letters. The communication topics were for advice, results or general updates
      (28%), medication queries (24%), appointment/admission coordination (20%),
      disease flare or other disease events (14%), psychosocial, school or transition
      issues (6%) and miscellaneous queries (8%). Of the most frequent communicators,
      those with juvenile idiopathic arthritis were the majority (85%). The remainder
      had other chronic inflammatory conditions. CONCLUSIONS: The communication and
      support needs of patients with chronic rheumatic diseases and their families
      extend beyond that which can be provided in the clinic environment. It is
      essential that funding for paediatric rheumatology services allows for staffing
      sufficient to meet this need.

PMID- 23531346
TI  - World Trauma Congress: when dreams come true.

PMID- 23531345
TI  - Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid
      mice limits muscle regeneration.
AB  - INTRODUCTION: Loss of adult stem cell function during aging contributes to
      impaired tissue regeneration. Here, we tested the aging-related decline in
      regeneration potential of adult stem cells residing in the skeletal muscle.
      METHODS: We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid
      Zmpste24-deficient mice (Zmpste24(-/-)) with accelerated aging phenotypes to
      investigate whether mutation in lamin A has an adverse effect on muscle
      stem/progenitor cell function. RESULTS: Our results indicate that MDSPCs isolated
      from Zmpste24(-/-) mice show reduced proliferation and myogenic differentiation.
      In addition, Zmpste24(-/-) MDSPCs showed impaired muscle regeneration, with a
      limited engraftment potential when transplanted into dystrophic muscle, compared
      with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24(-/-) MDSPCs to WT
      MDSPCs rescued the myogenic differentiation defect in vitro. CONCLUSIONS: These
      results demonstrate that adult stem/progenitor cell dysfunction contributes to
      impairment of tissue regeneration and suggest that factors secreted by functional
      cells are indeed important for the therapeutic effect of adult stem cells.

PMID- 23531347
TI  - Recombinant activated factor VII and aortic surgery.

PMID- 23531348
TI  - Quantifying diplopia with a questionnaire.
AB  - PURPOSE: To report a diplopia questionnaire (DQ) with a data-driven scoring
      algorithm. DESIGN: Cross-sectional study. PARTICIPANTS: To optimize questionnaire
      scoring, 147 adults with diplopic strabismus completed both the DQ and the Adult
      Strabismus-20 (AS-20) health-related quality-of-life (HRQOL) questionnaire. To
      assess test-retest reliability, 117 adults with diplopic strabismus. To assess
      responsiveness to surgery, 42 adults (46 surgeries). METHODS: The 10-item AS-20
      function subscale score (scored 0-100) was defined as the gold standard for
      severity. A range of weights was assigned to the responses and the gaze positions
      (from equal weighting to greater weighting of primary and reading). Combining all
      response option weights with all gaze position weights yielded 382848 scoring
      algorithms. We then calculated 382848 Spearman rank correlation coefficients
      comparing each algorithm with the AS-20 function subscale score. MAIN OUTCOME
      MEASURES: To optimize scoring, Spearman rank correlation coefficients (measuring
      agreement) between DQ scores and AS-20 function subscale scores. For test-retest
      reliability, 95% limits of agreement and intraclass correlation coefficient
      (ICC). For responsiveness, change in DQ score. RESULTS: For the 382 848 possible
      scoring algorithms, correlations with AS-20 function subscale score ranged from 
      0.64 (best correlated) to -0.55. The best-correlated algorithm had response
      option weights of 5 for rarely, 50 for sometimes, and 75 for often, and gaze
      position weights of 40 for straight ahead in the distance, 40 for reading, 1 for
      up, 8 for down, 4 for right, 4 for left, and 3 for other, totaling 100. There was
      excellent test-retest reliability with an ICC of 0.89 (95% confidence interval,
      0.84-0.92), and 95% limits of agreement were 30.9 points. The DQ score was
      responsive to surgery with a mean change of 51 +/- 34 (P<0.001). CONCLUSIONS: We
      have developed a data-driven scoring algorithm for the DQ, rating diplopia
      symptoms from 0 to 100. On the basis of correlations with HRQOL, straight-ahead
      and reading positions should be highly weighted. The DQ has excellent test-retest
      reliability and responsiveness, and may be useful in both clinical and research
      settings.

PMID- 23531349
TI  - Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple
      sclerosis.
AB  - PURPOSE: To report outcomes of ophthalmic evaluations in clinical studies of
      patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland)
      for multiple sclerosis (MS). DESIGN: Analysis done on pooled safety data (N =
      2615, all studies group) from 3 double-masked, randomized, parallel-group
      clinical trials (phase 2 core and extension >5 years, and phase 3 FREEDOMS and
      TRANSFORMS core and extension studies). PARTICIPANTS: Patients aged 18 to 55
      years (18-60 years in phase 2 study) diagnosed with relapsing-remitting MS were
      included. Patients with diabetes mellitus or macular edema (ME) at screening were
      excluded. INTERVENTION: Participants received fingolimod (0.5/1.25 mg), placebo,
      or interferon beta for the respective study durations. Ophthalmic examination
      included detailed eye history (at screening), visual acuity (VA) assessment,
      dilated ophthalmoscopy, optical coherence tomography (OCT), and fluorescein
      angiography (FA). MAIN OUTCOME MEASURES: Extensive ophthalmic monitoring was
      performed for all patients. While being studied, patients with abnormal findings
      on dilated ophthalmoscopy and OCT compatible with ME were further studied by FA.
      All locally diagnosed ME cases were centrally reviewed by the retina specialist
      (M.A.Z.) on the Data and Safety Monitoring Board. RESULTS: Among 2615 patients
      assessed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5
      mg: n = 4, 0.3%; 1.25 mg: n = 15, 1.2%). Most patients (n = 13, 68%) presented
      with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed
      within 3 to 4 months of treatment initiation in most cases (n = 13, 68%); 2
      patients had late onset (>12 months) ME. Of the 19 patients with ME, 5 (26%), all
      treated with fingolimod 1.25 mg, had a history of uveitis compared with 26 (1%)
      in the all studies group. In most cases (n = 16, 84%), ME resolved after
      discontinuing the study drug. Eleven patients required topical anti-inflammatory
      medications. No patient had further vision deterioration. CONCLUSIONS: Fingolimod
      0.5 mg is associated with a low incidence of ME in MS studies. Patients with a
      history of uveitis may be at an increased risk of developing ME. An ophthalmic
      examination before initiating fingolimod therapy and regular follow-up eye
      examinations during fingolimod therapy are recommended.

PMID- 23531350
TI  - Structure and clinical significance of central optic disc pits.
AB  - OBJECTIVE: To assess the structure of central optic disc pits (ODPs) using
      enhanced-depth imaging optical coherence tomography (EDI OCT) and to ascertain
      their clinical significance. DESIGN: Prospective, cross-sectional study.
      PARTICIPANTS: Patients with an ophthalmoscopically visible central ODP in either
      eye, irrespective of accompanying ocular disease, were enrolled from the neuro
      ophthalmology and glaucoma referral practices. Each subject with a central ODP
      was matched with 2 healthy subjects with normal-appearing optic disc within 5
      years of age. METHODS: Each participant received a complete ophthalmologic
      examination including standard automated perimetry, retinal nerve fiber layer
      (RNFL) thickness measurement by OCT, and serial horizontal and vertical cross
      sectional EDI OCT of the optic nerve head. MAIN OUTCOME MEASURES: Structure of
      the lamina cribrosa (LC) in relation to the central ODP in EDI OCT images.
      RESULTS: Eighteen eyes (13 subjects) with a central ODP and 52 healthy eyes (26
      controls) were included. Four eyes (2 subjects) with a central ODP were otherwise
      normal with intact macula, neuroretinal rim, RNFL, and visual field. Fourteen
      eyes (11 subjects) with a central ODP had glaucoma with glaucomatous neuroretinal
      rim thinning, RNFL loss, and corresponding visual field defect. No eye had
      associated maculopathy. On EDI OCT, the central ODP corresponded with a full
      thickness defect in the LC center with no serous retinal detachment or herniation
      of neural tissue through the LC defect. Central ODPs were separated from (type 1)
      or merged with (type 2) the LC opening for the central retinal vascular trunk. In
      control eyes, no LC defect was detected. CONCLUSIONS: Central ODPs are full
      thickness LC defects unassociated with maculopathy and different from
      glaucomatous acquired pits of the optic nerve, which represent focal laminar
      defect adjacent to the disc edge.

PMID- 23531351
TI  - Attitudes toward retirement of ophthalmology department chairs.
AB  - PURPOSE: To identify common perceptions and ideas about preparation and planning
      for retirement of chairs of academic departments of ophthalmology, determining
      areas of particular stress and proposing ways to better prepare for retirement.
      DESIGN: Cross-sectional study. PARTICIPANTS: One-hundred sixteen chairs of
      academic departments of ophthalmology in the United States. METHODS: A
      confidential online survey emailed to ophthalmology chairs. MAIN OUTCOME
      MEASURES: Surveys assessed demographics; current work schedule; perceptions,
      preparation, and planning for retirement; and retirement training for faculty and
      residents. RESULTS: Ninety-six department chairs responded to the survey (82%
      response rate). Most chairs anticipate retiring around age 70. Significantly,
      only 9% are looking forward to retirement. Reasons for delaying retirement
      include keeping active (37%), income/insurance/benefits (20%), and maintaining
      lifestyle (17%). The most common concern is financing retirement (46%). Forty
      percent anticipate their reason for retirement will be because of age or health,
      whereas 20% anticipate fatigue or burnout. Nearly half of the respondents have no
      specific plan upon retirement. Most respondents anticipate pursuing other
      interests (43%); 32% intend to spend time with family, vacationing, and
      travelling. Younger respondents are more concerned with the financial aspects of
      retirement while more senior respondents appear to delay retirement to keep
      active or because they enjoy their work. CONCLUSIONS: Retirement is a source of
      stress for many ophthalmology department chairs and many indicate financial
      preparation is their major concern. Despite this, the major reason for putting
      off retirement is a desire to keep active. Developing a retirement plan eases
      stress and engenders a feeling of confidence about the future.

PMID- 23531352
TI  - Immunologic graft rejection in descemet's stripping endothelial keratoplasty and
      penetrating keratoplasty for endothelial disease.
AB  - OBJECTIVE: To evaluate and compare the cumulative incidence and risk factors for
      first-episode immunologic graft rejection in Descemet's stripping automated
      endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) and to
      identify potential risk factors for rejection. DESIGN: Retrospective chart
      review. PARTICIPANTS: All patients who underwent PK or DSAEK for endothelial
      disease at the Department of Ophthalmology, North Shore LIJ, between January 2004
      and June 2010. METHODS: One hundred sixty-nine PK cases and 122 DSAEK cases were
      reviewed. All patients had a minimum of 3 months of follow-up, with median follow
      up of 36 months in the PK group and 29 months in the DSAEK group. MAIN OUTCOME
      MEASURES: Cumulative incidence of first-episode immunologic graft rejection in PK
      and DSAEK cohorts. Risk factors for graft rejection were reviewed. RESULTS:
      Cumulative incidence of rejection was not significantly different between the
      DSAEK and PK cohorts (P<0.1324). However, among patients without glaucoma, the
      risk of rejection in PK was higher than that in DSAEK (hazard ratio [HR], 5.56).
      Prior incisional glaucoma surgery imparted a 3.15 times greater risk of rejection
      regardless of transplant type. Phakic patients were more likely to experience
      rejection than patients with a posterior chamber intraocular lens (HR, 3.23;
      P<0.0266), but not more likely than those with an anterior chamber intraocular
      lens or who were aphakic. Graft failure occurred within 6 months in 31% of PK
      rejections and none of the DSAEK rejections. CONCLUSIONS: Descemet's stripping
      automated endothelial keratoplasty and PK did not show a statistically
      significant difference in the incidence of rejection; however, among
      nonglaucomatous eyes, there were significantly fewer rejections in those that
      underwent DSAEK.

PMID- 23531353
TI  - Enhanced depth imaging optical coherence tomography of optic nerve head drusen.
AB  - OBJECTIVE: To assess the value of enhanced depth imaging optical coherence
      tomography (EDI OCT) in diagnosing and evaluating optic nerve head drusen (ONHD)
      compared with conventional diagnostic methods. DESIGN: Prospective, comparative,
      cross-sectional study. PARTICIPANTS: Thirty-four patients with clinically visible
      or suspected ONHD in either eye based on dilated optic disc examination or optic
      disc stereophotography and without ocular comorbidity. METHODS: Spectral-domain
      OCT of the optic nerve head in both conventional (non-EDI) and EDI modes,
      ultrasound B-scan, and standard automated perimetry were performed on both eyes
      of all participants. MAIN OUTCOME MEASURES: Detection and findings of ONHD
      between EDI OCT and conventional diagnostic methods. RESULTS: Sixty-eight eyes
      were clinically classified into 3 groups: 32 eyes with definite ONHD, 25 eyes
      with suspected ONHD, and 11 normal-appearing fellow eyes. In the definite ONHD
      group, EDI OCT, non-EDI OCT, and ultrasound B-scan were positive for ONHD in all
      eyes and visual field (VF) was abnormal in 24 eyes. In the suspected ONHD group,
      EDI OCT, non-EDI OCT, ultrasound B-scan, and VF were positive in 17, 14, 7, and 3
      eyes, respectively; 8 eyes had no evidence of ONHD in any of the tests. In normal
      appearing fellow eyes, EDI OCT, non-EDI OCT, ultrasound B-scan, and VF were
      positive in 3, 1, 1, and 0 eyes, respectively; 4 eyes had no evidence of ONHD in
      any of the tests. Enhanced depth imaging OCT had a significantly higher ONHD
      detection rate than ultrasound B-scan in all eyes (52/68 eyes vs. 40/68 eyes;
      P<0.001), in eyes with clinically suspected ONHD or normal-appearing fellow eyes
      (20/36 eyes vs. 8/36 eyes; P<0.001), and in eyes with clinically suspected ONHD
      (17/25 eyes vs. 7/25 eyes; P = 0.002). Enhanced depth imaging OCT-detected ONHD
      appeared as signal-poor regions surrounded by short, hyper-reflective bands or
      isolated/clustered hyper-reflective bands without a signal-poor core. In non-EDI
      OCT, posterior surfaces of the ONHD and deep-seated hyper-reflective bands were
      invisible or less clear than in EDI OCT. CONCLUSIONS: Enhanced depth imaging OCT
      detects lesions likely representing ONHD more often and better assesses their
      shape and structure than conventional tests.

PMID- 23531355
TI  - Epigenetics and Chromatin: Interactions and processes Boston, MA, USA. 11-13
      March 2013. Abstracts.

PMID- 23531354
TI  - Patchwork: allele-specific copy number analysis of whole-genome sequenced tumor
      tissue.
AB  - Whole-genome sequencing of tumor tissue has the potential to provide
      comprehensive characterization of genomic alterations in tumor samples. We
      present Patchwork, a new bioinformatic tool for allele-specific copy number
      analysis using whole-genome sequencing data. Patchwork can be used to determine
      the copy number of homologous sequences throughout the genome, even in aneuploid
      samples with moderate sequence coverage and tumor cell content. No prior
      knowledge of average ploidy or tumor cell content is required. Patchwork is
      freely available as an R package, installable via R-Forge (http://patchwork.r
      forge.r-project.org/). 

PMID- 23531356
TI  - Psychiatrists' perceptions of the clinical importance, assessment and management
      of patient functioning in schizophrenia in Europe, the Middle East and Africa.
AB  - BACKGROUND: It has been estimated that as many as two thirds of patients with
      schizophrenia are unable to perform basic personal and social roles or
      activities. Occupational functioning and social functioning, as well as
      independent living, are considered as core domains of patient functioning.
      Improvement in patient functioning has also been recognized as an important
      treatment goal in guidelines and an important outcome by regulatory agencies.
      Nevertheless, information is lacking on how these aspects are being considered by
      psychiatrists across the world and how they are being assessed and managed.
      METHODS: The 'Europe, the Middle East and Africa functioning survey' was designed
      to canvas opinions of psychiatrists across these regions to ascertain their
      perceptions of the clinical importance, assessment and management of functioning
      amongst their patients with schizophrenia. The survey comprised 17 questions and
      was conducted from March to April 2011 in 42 countries. Data collected included
      the demographics of respondents and their opinions regarding personal and social
      functioning in patients with schizophrenia. RESULTS: Results were obtained from
      4,163 clinicians. Psychiatrists estimated that more than two thirds (70%) of
      their patients with schizophrenia showed impaired or very poor levels of
      functioning. The majority of psychiatrists (92%) believed that personal and
      social functioning was an important treatment goal for patients with
      schizophrenia, and 91% believed it was an important goal for patients' families.
      The majority of psychiatrists (55%) assess the personal and social functioning of
      their patient at each visit; however, 81% reported that they determine the level
      of functioning through clinical interview and not by using a specific assessment
      scale. To manage personal and social functioning in their patients, 26% of
      psychiatrists prefer pharmacological interventions, whereas 46% prefer
      psychosocial interventions. CONCLUSION: Psychiatrists recognize that functioning
      is impaired/very poor in patients with schizophrenia, and there is still an
      important need to address functioning as a main treatment goal for patients with
      schizophrenia.

PMID- 23531358
TI  - Prevalence and correlates of suicidal ideation among Operation Enduring Freedom
      and Operation Iraqi Freedom veterans.
AB  - BACKGROUND: We sought to determine the prevalence and correlates of suicidal
      ideation (SI) among Operation Enduring Freedom and Operation Iraqi Freedom
      (OEF/OIF) veterans following the Department of Veterans Affairs' (VA) 2007
      implementation of required brief SI assessments for veterans who screen positive
      for depression and post-traumatic stress disorder. METHODS: We retrospectively
      identified OEF/OIF veterans screened for depression using the Patient Health
      Questionnaire (PHQ-2) between April 2008 and September 2009 at three
      geographically-distinct VA Medical Centers' primary care or mental health
      clinics. Veteran responses to a two-item risk assessment tool (VA Pocket Card) or
      PHQ-9 9th item, administered following a positive depression screen (PHQ-2>=3),
      were determined using manual chart review. Generalized estimating equations were
      used to calculate adjusted odds ratios for demographic and clinical correlates of
      positive SI assessments. RESULTS: Of 1340 OEF/OIF veterans with positive
      depression screens, 32.4% reported SI. In multivariate models, odds of SI were
      lower for non-Hispanic white veterans (AOR=0.68) and greater for those with PHQ
      2>=5 (AOR=1.87), depression (AOR=1.45), bipolar disorder/schizophrenia
      (AOR=2.84), and 2 or >=3 diagnoses (AORs=1.59 and 2.49, respectively).
      LIMITATIONS: Study findings may not be generalizable to non-veteran patient
      populations and the study does not address the reliability and validity of tools
      employed for brief suicidal ideation assessment. CONCLUSIONS: SI is common among
      OEF/OIF veterans who receive VA care, perhaps more so among non-white veterans.
      Targeting veterans with higher PHQ-2 scores for SI assessment should be
      considered to reduce patient and administrative burden.

PMID- 23531357
TI  - Continuing difficulties in interpreting CNV data: lessons from a genome-wide CNV
      association study of Australian HNPCC/lynch syndrome patients.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome
      (LS) is a cancer syndrome characterised by early-onset epithelial cancers,
      especially colorectal cancer (CRC) and endometrial cancer. The aim of the current
      study was to use SNP-array technology to identify genomic aberrations which could
      contribute to the increased risk of cancer in HNPCC/LS patients. METHODS:
      Individuals diagnosed with HNPCC/LS (100) and healthy controls (384) were
      genotyped using the Illumina Human610-Quad SNP-arrays. Copy number variation
      (CNV) calling and association analyses were performed using Nexus software, with
      significant results validated using QuantiSNP. TaqMan Copy-Number assays were
      used for verification of CNVs showing significant association with HNPCC/LS
      identified by both software programs. RESULTS: We detected copy number (CN) gains
      associated with HNPCC/LS status on chromosome 7q11.21 (28% cases and 0% controls,
      Nexus; p =3.60E-20 and QuantiSNP; p < 1.00E-16) and 16p11.2 (46% in cases, while
      a CN loss was observed in 23% of controls, Nexus; p = 4.93E-21 and QuantiSNP; p =
      5.00E-06) via in silico analyses. TaqMan Copy-Number assay was used for
      validation of CNVs showing significant association with HNPCC/LS. In addition,
      CNV burden (total CNV length, average CNV length and number of observed CNV
      events) was significantly greater in cases compared to controls. CONCLUSION: A
      greater CNV burden was identified in HNPCC/LS cases compared to controls
      supporting the notion of higher genomic instability in these patients. One
      intergenic locus on chromosome 7q11.21 is possibly associated with HNPCC/LS and
      deserves further investigation. The results from this study highlight the
      complexities of fluorescent based CNV analyses. The inefficiency of both CNV
      detection methods to reproducibly detect observed CNVs demonstrates the need for
      sequence data to be considered alongside intensity data to avoid false positive
      results.

PMID- 23531359
TI  - Extra-curricular supervised training at an academic hospital: is 200 hours the
      threshold for medical students to perform well in an emergency room?
AB  - INTRODUCTION: Due to high number of jobs in Emergency Medicine (EM) and the lack
      of specialist to work in this field, recent graduates work in the emergency room
      straight after medical school. Additional courses on EM are available through
      Academic Leagues. This organizations offer lectures and supervised extra
      curricular practical activities in their teaching university-affiliated hospital.
      The objectives of the present study are to assess the influence of hours
      undertaken in the extra-curricular practical activities on the performance and
      confidence of students in carrying out the different procedures in the emergency
      department, and on their own perception of how well they did. Also, to assess the
      influence the practical activities have on student's future choice of specialty.
      METHODS: A Cross-sectional study conducted by collecting data through a
      questionnaire. 102 eligible individuals were included and divided into two groups
      according to the number of extra-curricular hours performed (Group 1- up to 200
      hours and Group 2- over 200 hours). RESULTS: Students in Group 2 (over 200 hours)
      had a greater number of procedures performed on all variables evaluated, in
      particular, initial patient care (mean 363.8 vs.136.905 in Group 1 - p = 0.001),
      Simple Sutures (mean of 96.2 vs 33.980 respectively) ( p = 0.00003). To determine
      patient follow-up by the student, the number of initial patient care was
      correlated with number of discharge procedures performed (in Group 1, 49.6% of
      patients were not followed up and discharged by the same students who first
      talked to them in the hospital. While in Group 2, this value becomes 29.4 % -
      values for Group 1 - p = 0.011 and Group 2 - p = 0.117). Regarding the influence
      of the practical extra-curricular activities, 76.5% of the total reported that it
      had influenced their choice of future specialty. CONCLUSIONS: The aptitude,
      confidence and skill of students are closely linked to the practice time (number
      of training hours served). Two hundred hours appeared to be a relatively
      significant time for the student to demonstrate good conduct and ability.
      Practical extra-curricular activities had the ability to influence the future
      choice of specialty, either positively or negatively.

PMID- 23531361
TI  - Multiday acute sodium bicarbonate intake improves endurance capacity and reduces
      acidosis in men.
AB  - BACKGROUND: The purpose was to investigate the effects of one dose of NaHCO3 per
      day for five consecutive days on cycling time-to-exhaustion (Tlim) at 'Critical
      Power' (CP) and acid-base parameters in endurance athletes. METHODS: Eight
      trained male cyclists and triathletes completed two exercise periods in a
      randomized, placebo-controlled, double-blind interventional crossover
      investigation. Before each period, CP was determined. Afterwards, participants
      completed five constant-load cycling trials at CP until volitional exhaustion on
      five consecutive days, either after a dose of NaHCO3 (0.3 g.kg-1 body mass) or
      placebo (0.045 g.kg-1 body mass NaCl). RESULTS: Average Tlim increased by 23.5%
      with NaHCO3 supplementation as compared to placebo (826.5 +/- 180.1 vs. 669.0 +/-
      167.2 s; P = 0.001). However, there was no time effect for Tlim (P = 0.375).
      [HCO3-] showed a main effect for condition (NaHCO3: 32.5 +/- 2.2 mmol.l-1;
      placebo: 26.2 +/- 1.4 mmol.l-1; P < 0.001) but not for time (P = 0.835). NaHCO3
      supplementation resulted in an expansion of plasma volume relative to placebo (P
      = 0.003). CONCLUSIONS: The increase in Tlim was accompanied by an increase in
      [HCO3-], suggesting that acidosis might be a limiting factor for exercise at CP.
      Prolonged NaHCO3 supplementation did not lead to a further increase in [HCO3-]
      due to the concurrent elevation in plasma volume. This may explain why Tlim
      remained unaltered despite the prolonged NaHCO3 supplementation period. Ingestion
      of one single NaHCO3 dose per day before the competition during multiday
      competitions or tournaments might be a valuable strategy for performance
      enhancement. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov
      Identifier NCT01621074.

PMID- 23531360
TI  - Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of
      Polycomb target genes.
AB  - BACKGROUND: DNA methylation and the Polycomb repression system are epigenetic
      mechanisms that play important roles in maintaining transcriptional repression.
      Recent evidence suggests that DNA methylation can attenuate the binding of
      Polycomb protein components to chromatin and thus plays a role in determining
      their genomic targeting. However, whether this role of DNA methylation is
      important in the context of transcriptional regulation is unclear. RESULTS: By
      genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark,
      H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that
      hypomethylation leads to widespread H3K27me3 redistribution, in a manner that
      reflects the local DNA methylation status in wild-type cells. Unexpectedly, we
      observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb
      target gene promoters in DNA hypomethylated cells, including Hox gene clusters.
      Importantly, we show that many of these genes become ectopically expressed in DNA
      hypomethylated cells, consistent with loss of Polycomb-mediated repression.
      CONCLUSIONS: An intact DNA methylome is required for appropriate Polycomb
      mediated gene repression by constraining Polycomb Repressive Complex 2 targeting.
      These observations identify a previously unappreciated role for DNA methylation
      in gene regulation and therefore influence our understanding of how this
      epigenetic mechanism contributes to normal development and disease.

PMID- 23531362
TI  - Metabolic syndrome and shift work: a systematic review.
AB  - The aim of this systematic review was to examine the association between shift
      work and metabolic syndrome (MetS) as well as the potential confounders
      investigated. A systematic search was conducted with the aim of finding original
      articles on the association between shift work and MetS. The included articles
      were chosen based on established inclusion criteria; their methodological quality
      was assessed using a validated quality checklist. A total of 10 articles were
      included in this review. The majority of the studies were classified as having a
      low risk of bias. The definitions of MetS and shift work varied between studies.
      Among the ten studies, eight found a positive association between shift work and
      MetS after controlling for socio-demographic and behavioral factors. Only three
      studies included sleep duration as a confounder, and these studies presented
      discordant results. We conclude that there was insufficient evidence regarding
      the association between shift work and prevalent MetS when the confounders are
      taken into account. 

PMID- 23531364
TI  - The scientific production in trauma of an emerging country.
AB  - BACKGROUND: The study aims to examine whether the end of specialty in trauma
      surgery in 2003 influenced the scientific productivity of the area in Brazil.
      METHODS: We identified and classified the manuscripts and their authors, from
      databases such as PubMed, Scielo and Plataforma Lattes and sites like Google, in
      addition to the list of members of SBAIT, the sole society in Brazil to
      congregate surgeons involved in trauma care in the country. We applied
      statistical tests to compare the periods of 1997-2003 and 2004-2010. We also
      analyzed the following variables: impact factor of journals in which manuscripts
      were published, journals, regional origin of authors, time since graduation, and
      conducting post-doctorate abroad. RESULTS: We observed a significant increase in
      publication rates of the analyzed groups over the years. There was a predominance
      of quantitative studies from the Southeast (especially the state of Sao Paulo).
      More time elapsed after graduation and the realization of postdoctoral studies
      abroad influenced the individual scientific productivity. CONCLUSION: The number
      of articles published by authors from the area of trauma has been growing over
      the past 14 years in Brazil. The end of the specialty in trauma surgery in the
      country did not influence the scientific productivity in the area.

PMID- 23531363
TI  - Is quality of diet associated with the microvasculature? An analysis of diet
      quality and retinal vascular calibre in older adults.
AB  - It is unknown whether diet quality is associated with microvascular structure.
      The present study aimed to investigate the relationship between diet quality,
      reflecting adherence to dietary guidelines, with retinal microvascular calibre in
      older adults. The dietary data of 2720 Blue Mountains Eye Study participants,
      aged 50+ years, were collected using a semi-quantitative FFQ. A modified version
      of the Healthy Eating Index for Australians was developed to determine total diet
      scores (TDS). Fundus photographs were taken and retinal vascular calibre measured
      using computer-assisted techniques and summarised. After adjusting for age, sex,
      BMI, mean arterial blood pressure, smoking, serum glucose, leucocyte count and
      history of diagnosed stroke or CHD, persons with higher TDS had healthier retinal
      vessels cross-sectionally, with wider retinal arteriolar calibre (by
      approximately 3 MUm, comparing the highest with the lowest quartile of TDS,
      Ptrend = 0.0001) and narrower retinal venular calibre (by approximately 2.5 MUm;
      Ptrend = 0.02). In younger subjects aged <=65 years, increasing TDS (lowest to
      the highest quartile) was associated with healthier retinal vessels:
      approximately 4.4 MUm wider retinal arteriolar (Ptrend < 0.0001) and
      approximately 2.3 MUm narrower venular calibre (Ptrend = 0.03). After
      multivariable adjustment, however, baseline TDS were not associated with retinal
      arteriolar (Ptrend = 0.89) or venular calibre (Ptrend = 0.25), 5 years later.
      Also, baseline TDS were not associated with the 5-year change in retinal
      arteriolar (beta = 0.14; P=0.29) or venular calibre (beta = - 0.26; P=0.07).
      Greater compliance with published dietary guidelines (higher diet quality) was
      cross-sectionally associated with wider retinal arterioles and narrower venules,
      indicating better retinal microvascular health.

PMID- 23531365
TI  - Hospital policy for prevention of infection after neuraxial blocks in obstetrics.
AB  - Even though most regional anesthesia textbooks and articles about infectious
      complications associated with central neuraxial blocks underline the necessity of
      surgical asepsis, none offers a clear and precise procedure. This protocol is
      intended to reduce variability of practices, and is felt to be stringent enough
      to be effective and liberal enough to be fully implemented. Any person involved
      with the procedure must wear a cap and a new face mask. The patient also should
      wear a cap. The anesthesiologist, wearing his usual operating room clothing, must
      wash his hands with an antiseptic soap solution, dry them on a sterile towel and
      wear sterile gloves. The patient's back should be disinfected at least twice
      (alcohol-iodine, alcoholic solution of chlorhexidine or of povidone-iodine).
      Disposable equipment only must be used. Drugs must be prepared contemporaneously
      and in a sterile manner (collar of non-sterilized ampoules cleaned with alcohol).
      The solution is drawn up through the filter (contained in the epidural set) but
      injected after filter removal. Infusion of sterile mixtures is preferable to top
      ups, which require frequent disconnections that may cause hub colonization.
      Manipulation of the hub of the catheter must be preceded both by antiseptic hand
      washing and by swabbing with sterilized gauze soaked with 70% alcohol. Catheter
      removal requires only antiseptic hand washing in most circumstances. Wearing mask
      and gloves and improving skin disinfection practices are believed to be the more
      important parts of this protocol.

PMID- 23531366
TI  - RNA sequencing reveals sexually dimorphic gene expression before gonadal
      differentiation in chicken and allows comprehensive annotation of the W
      chromosome.
AB  - BACKGROUND: Birds have a ZZ male: ZW female sex chromosome system and while the Z
      linked DMRT1 gene is necessary for testis development, the exact mechanism of sex
      determination in birds remains unsolved. This is partly due to the poor
      annotation of the W chromosome, which is speculated to carry a female
      determinant. Few genes have been mapped to the W and little is known of their
      expression. RESULTS: We used RNA-seq to produce a comprehensive profile of gene
      expression in chicken blastoderms and embryonic gonads prior to sexual
      differentiation. We found robust sexually dimorphic gene expression in both
      tissues pre-dating gonadogenesis, including sex-linked and autosomal genes. This
      supports the hypothesis that sexual differentiation at the molecular level is at
      least partly cell autonomous in birds. Different sets of genes were sexually
      dimorphic in the two tissues, indicating that molecular sexual differentiation is
      tissue specific. Further analyses allowed the assembly of full-length transcripts
      for 26 W chromosome genes, providing a view of the W transcriptome in embryonic
      tissues. This is the first extensive analysis of W-linked genes and their
      expression profiles in early avian embryos. CONCLUSION: Sexual differentiation at
      the molecular level is established in chicken early in embryogenesis, before
      gonadal sex differentiation. We find that the W chromosome is more
      transcriptionally active than previously thought, expand the number of known
      genes to 26 and present complete coding sequences for these W genes. This
      includes two novel W-linked sequences and three small RNAs reassigned to the W
      from the Un_Random chromosome.

PMID- 23531367
TI  - Up-regulation of immunoglobulin G gene expression in the hippocampus of rats
      subjected to acute immobilization stress.
AB  - Immunoglobulin G (IgG) is thought to be produced by matured B lymphocytes,
      however, it was recently found to be synthesized in neurons of the brain,
      especially showing higher expression level in the hippocampus. To study the
      possible effects of IgG in the hippocampus, we examined IgG protein and mRNA
      expressions in rat hippocampal neurons with immunohistochemistry,
      immunofluorescence, in situ hybridization and laser microdissection-assisted RT
      PCR. Increased IgG expressions at both protein and mRNA levels were detected in
      the hippocampus of an acute immobilization stress model of rat. No change was
      observed in the cortex or the thalamus. Furthermore, the microtubule-associated
      protein 2 (MAP2) and beta III tubulin proteins did not show significant changes.
      Based on these findings, we hypothesize that hippocampal IgG may play a key role
      in adverse circumstances such as stress. The finding of increased IgG expression
      in the hippocampus following stress may also provide possibilities for developing
      antidepressant medication.

PMID- 23531368
TI  - Optimization and visualization of the edge weights in optimal assignment methods
      for virtual screening.
AB  - BACKGROUND: Ligand-based virtual screening plays a fundamental part in the early
      drug discovery stage. In a virtual screening, a chemical library is searched for
      molecules with similar properties to a query molecule by means of a similarity
      function. The optimal assignment of chemical graphs has proven to be a valuable
      similarity function for many cheminformatic tasks, such as virtual screening. The
      optimal assignment assumes all atoms of a query molecule to be equally important,
      which is not realistic depending on the binding mode of a ligand. The importance
      of a query molecule's atoms can be integrated in the optimal assignment by
      weighting the assignment edges. We optimized the edge weights with respect to the
      virtual screening performance by means of evolutionary algorithms. Furthermore,
      we propose a visualization approach for the interpretation of the edge weights.
      RESULTS: We evaluated two different evolutionary algorithms, differential
      evolution and particle swarm optimization, for their suitability for optimizing
      the assignment edge weights. The results showed that both optimization methods
      are suited to optimize the edge weights. Furthermore, we compared our approach to
      the optimal assignment with equal edge weights and two literature similarity
      functions on a subset of the Directory of Useful Decoys using sophisticated
      virtual screening performance metrics. Our approach achieved a considerably
      better overall and early enrichment performance. The visualization of the edge
      weights enables the identification of substructures that are important for a good
      retrieval of ligands and for the binding to the protein target. CONCLUSIONS: The
      optimization of the edge weights in optimal assignment methods is a valuable
      approach for ligand-based virtual screening experiments. The approach can be
      applied to any similarity function that employs the optimal assignment method,
      which includes a variety of similarity measures that have proven to be valuable
      in various cheminformatic tasks. The proposed visualization helps to get a better
      understanding of the binding mode of the analyzed query molecule.

PMID- 23531369
TI  - Is the reporting timeliness gap for avian flu and H1N1 outbreaks in global health
      surveillance systems associated with country transparency?
AB  - BACKGROUND: This study aims to evaluate the length of time elapsed between
      reports of the same incidents related to avian flu and H1N1 outbreaks published
      by the WHO and ProMED-mail, the two major global health surveillance systems,
      before and after the amendment of the International Health Regulations in 2005
      (IHR 2005) and to explore the association between country transparency and this
      timeliness gap. METHODS: We recorded the initial release dates of each report
      related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the
      matching outbreak report from ProMED-mail, a non-governmental program for
      monitoring emerging diseases, from 2003 to the end of June 2009. The timeliness
      gap was calculated as the difference in days between the report release dates of
      the matching outbreaks in the WHO and ProMED-mail systems. Civil liberties scores
      were collected as indicators of the transparency of each country. The Human
      Development Index and data indicating the density of physicians and nurses were
      collected to reflect countries' development and health workforce statuses. Then,
      logistic regression was performed to determine the correlation between the
      timeliness gap and civil liberties, human development, and health workforce
      status, controlling for year. RESULTS: The reporting timeliness gap for avian flu
      and H1N1 outbreaks significantly decreased after 2003. On average, reports were
      posted 4.09 (SD = 7.99) days earlier by ProMED-mail than by the WHO. Countries
      with partly free (OR = 5.77) and free civil liberties scores (OR = 10.57) had
      significantly higher likelihoods of longer timeliness gaps than non-free
      countries. Similarly, countries with very high human development status had
      significantly higher likelihoods of longer timeliness gaps than countries with
      middle or low human development status (OR = 5.30). However, no association
      between the timeliness gap and health workforce density was found. CONCLUSION:
      The study found that the adoption of IHR 2005, which contributed to countries'
      awareness of the importance of timely reporting, had a significant impact in
      improving the reporting timeliness gap. In addition, the greater the civil
      liberties in a country (e.g., importance of freedom of the media), the longer the
      timeliness gap.

PMID- 23531370
TI  - SML resist processing for high-aspect-ratio and high-sensitivity electron beam
      lithography.
AB  - A detailed process characterization of SML electron beam resist for high-aspect
      ratio nanopatterning at high sensitivity is presented. SML contrast curves were
      generated for methyl isobutyl ketone (MIBK), MIBK/isopropyl alcohol (IPA) (1:3),
      IPA/water (7:3), n-amyl acetate, xylene, and xylene/methanol (3:1) developers.
      Using IPA/water developer, the sensitivity of SML was improved considerably and
      found to be comparable to benchmark polymethylmethacrylate (PMMA) resist without
      affecting the aspect ratio performance. Employing 30-keV exposures and ultrasonic
      IPA/water development, an aspect ratio of 9:1 in 50-nm half-pitch dense grating
      patterns was achieved representing a greater than two times improvement over
      PMMA. Through demonstration of 25-nm lift-off features, the pattern transfer
      performance of SML is also addressed.

PMID- 23531371
TI  - Microbiology and antimicrobial treatment of pediatric cervical lymphadenitis
      requiring surgical intervention.
AB  - BACKGROUND: Acute cervical lymphadenitis is a common condition often times
      requiring antibiotic therapy and possible surgical drainage. The objective of
      this study was to describe the clinical characteristics, diagnostic and
      therapeutic management of children requiring surgical drainage for acute cervical
      lymphadenitis. METHODS: A retrospective, descriptive study was performed at a
      Midwestern US tertiary-care children's hospital on all immunocompetent children
      who underwent an incision and drainage procedure of cervical lymphadenitis from
      January 1999 to July 2009. RESULTS: A total of 277 patients were identified.
      Males represented 51% and the median age was 28 months (IQR: 13-59).
      Lymphadenitis was unilateral in 243 (87.7%) cases and bilateral in 19 (6.9%).
      Median length of hospital stay was 4 days (IQR: 3-5). Aerobic, anaerobic, acid
      fast bacillus (AFB), and fungal cultures were obtained intraoperatively in 99%,
      98%, 82%, and 78% of cases, respectively. However no fungal cultures were
      positive and only 1% of anaerobic and 2% of AFB cultures were positive. The most
      common bacterial etiology was Staphylococcus aureus (35.7%) and Streptococcus
      pyogenes (18.8%). Of all cultures, 32% were negative. Overall, 22% were positive
      for methicillin susceptible S. aureus (MSSA) and 13.7% for methicillin resistant
      S. aureus (MRSA), with 96% MSSA and 100% MRSA susceptible to clindamycin. Median
      duration of discharge antibiotics prescribed was 10 days (IQR: 7-11). Only 12
      (4.5%) patients required a repeat incision and drainage within 3 months.
      CONCLUSIONS: A single antibiotic that treats S. pyogenes and S. aureus should be
      the empiric antibiotic for cervical lymphadenitis requiring incision and drain.
      We recommend sending only aerobic cultures intraoperatively as a routine practice
      as other pathogens are rare.

PMID- 23531372
TI  - Neuropathic midfoot deformity: associations with ankle and subtalar joint motion.
AB  - BACKGROUND: Neuropathic deformities impair foot and ankle joint mobility, often
      leading to abnormal stresses and impact forces. The purpose of our study was to
      determine differences in radiographic measures of hind foot alignment and ankle
      joint and subtalar joint motion in participants with and without neuropathic
      midfoot deformities and to determine the relationships between radiographic
      measures of hind foot alignment to ankle and subtalar joint motion in
      participants with and without neuropathic midfoot deformities. METHODS: Sixty
      participants were studied in three groups. Forty participants had diabetes
      mellitus (DM) and peripheral neuropathy (PN) with 20 participants having
      neuropathic midfoot deformity due to Charcot neuroarthropathy (CN), while 20
      participants did not have deformity. Participants with diabetes and neuropathy
      with and without deformity were compared to 20 young control participants without
      DM, PN or deformity. Talar declination and calcaneal inclination angles were
      assessed on lateral view weight bearing radiograph. Ankle dorsiflexion, plantar
      flexion and subtalar inversion and eversion were assessed by goniometry. RESULTS:
      Talar declination angle averaged 34+/-9, 26+/-4 and 23+/-3 degrees in
      participants with deformity, without deformity and young control participants,
      respectively (p< 0.010). Calcaneal inclination angle averaged 11+/-10, 18+/-9 and
      21+/-4 degrees, respectively (p< 0.010). Ankle plantar flexion motion averaged
      23+/-11, 38+/-10 and 47+/-7 degrees (p<0.010). The association between talar
      declination and calcaneal inclination angles with ankle plantar flexion range of
      motion is strongest in participants with neuropathic midfoot deformity.
      Participants with talonavicular and calcaneocuboid dislocations result in the
      most severe restrictions in ankle joint plantar flexion and subtalar joint
      inversion motions. CONCLUSIONS: An increasing talar declination angle and
      decreasing calcaneal inclination angle is associated with decreases in ankle
      joint plantar flexion motion in individuals with neuropathic midfoot deformity
      due to CN that may contribute to excessive stresses and ultimately plantar
      ulceration of the midfoot.

PMID- 23531373
TI  - Proteomic profiling in schizophrenia: enabling stratification for more effective
      treatment.
AB  - Schizophrenia is a heterogeneous psychiatric disorder characterized by an array
      of clinical manifestations. Although the best known manifestations include
      serious effects on mood and behavior, patients can also display co-morbidities,
      including immune system or metabolic abnormalities. Thorough characterization of
      these conditions using proteomic profiling methods has increased our knowledge of
      these molecular differences and has helped to unravel the complexity and
      heterogeneity of this debilitating condition. This could lead to patient
      stratification through characterization of biochemically different subtypes of
      the disease. In addition, proteomic methods have recently been used for molecular
      characterization of the mechanism of action of antipsychotic medications in both
      preclinical models and patients. This has resulted in identification of molecular
      panels that show some promise for prediction of response or for monitoring
      treatment outcome. This review describes how proteomic profiling methods can
      impact the future of schizophrenia diagnosis and therapeutics, and facilitate
      personalized medicine approaches for more effective treatment management of
      schizophrenia patients. 

PMID- 23531374
TI  - The assessment of vigilance: normative data on the Siesta sustained attention
      test.
AB  - OBJECTIVE: In several modern society duties individuals have to maintain their
      attention or vigilance over prolonged periods of time, even if the monitoring
      task is monotonous. The aim of our study was to obtain reference data on the 60
      minute monotonous Siesta sustained attention test. METHODS: Normative data were
      gathered in an age-stratified sample of 234 healthy participants (118 men; 116
      women) between the ages of 20 and 79 years. The impact of age, gender, time of
      day, and time on task during performance was analyzed. RESULTS: At least 20
      participants from each age group and gender group were tested either in the
      morning or in the afternoon. The sample sizes were only smaller in the age group
      of 70 to 79 years. There was a notable age effect on all performance measures,
      with an increase in reaction times and false response rates from the youngest to
      the oldest group as well as a decrease in correct reactions with increasing age.
      Statistical analysis revealed no differences in speed and accuracy measures
      between men and women participants. There was no notable time-of-day effect but a
      clear impact of time-on-task speed and of correct reactions during the course of
      the test. The vigilance decrement had already occurred during the first half of
      the test. CONCLUSIONS: Our results provide a normative database of performance
      parameters for different age groups in healthy adult participants. As sustained
      attention is sensitive to sleep loss and nonrestorative sleep, our data can be
      used as a reference for performance-based assessment of daytime sleepiness in
      participants with hypersomnia.

PMID- 23531375
TI  - Propionic and butyric acids, formed in the caecum of rats fed highly fermentable
      dietary fibre, are reflected in portal and aortic serum.
AB  - SCFA are important end products formed during colonic fermentation of dietary
      fibre (DF). It has been suggested that propionic and butyric acids affect
      metabolic parameters, low-grade systemic inflammation, insulin resistance and
      obesity. The aim of the present study was to investigate whether the various SCFA
      profiles observed after fermentation in the caecum of rats fed pectin, guar gum
      and fructo-oligosaccharides (FOS) were also represented in hepatic portal and
      aortic serum. The SCFA in serum were extracted using hollow fibre-supported
      liquid membrane extraction before GLC analysis. The concentrations of acetic,
      propionic and butyric acids in caecal content correlated well with those in
      portal serum (P< 0.001) for all the three diets. A weaker correlation was found
      for propionic and butyric acids between the caecal content and aortic serum (P<
      0.05). Butyric acid concentration in caecal content was also reflected in the
      aortic serum (P= 0.019) of rats fed FOS. FOS gave rather low amounts of the SCFA,
      especially butyric acid, but caecal tissue weight was higher with FOS than with
      the other two diets. This may be explained by rapid fermentation and quick
      utilisation/absorption of the SCFA. The present study also showed that propionic
      acid was metabolised/utilised to a higher extent than butyric acid by colonocytes
      before reaching the liver. We conclude that the formation of propionic and
      butyric acids in the caecum is reflected by increased concentrations in the
      aortic blood. This approach may therefore simplify the evaluation and study of
      SCFA from DF in human subjects.

PMID- 23531376
TI  - The world of trauma working together.

PMID- 23531377
TI  - Thiazolidinedione usage is associated with decreased response to clopidogrel in
      DM patients.

PMID- 23531379
TI  - When enough is enough: how the decision was made to stop the FEAST trial: data
      and safety monitoring in an African trial of Fluid Expansion As Supportive
      Therapy (FEAST) for critically ill children.
AB  - In resource-rich countries, bolus fluid expansion is routinely used for the
      treatment of poor perfusion and shock, but is less commonly used in many African
      settings. Controversial results from the recently completed FEAST (Fluid
      Expansion As Supportive Therapy) trial in African children have raised questions
      about the use of intravenous bolus fluid for the treatment of shock. Prior to the
      start of the trial, the Independent data monitoring committee (IDMC) developed
      stopping rules for the proof of benefit that bolus fluid resuscitation would
      bring. Although careful safety monitoring was put in place, there was less
      expectation that bolus fluid expansion would be harmful and differential stopping
      rules for harm were not formulated.In July 2010, two protocol amendments were
      agreed to increase the sample size from 2,880 to 3,600 children, and to increase
      bolus fluid administration. There was a non-significant trend against bolus
      treatment, but although the implications were discussed, the IDMC did not comment
      on the results, or on the amendments, in order to avoid inadvertent partial
      unblinding of the study.In January 2011, the trial was stopped for futility, as
      the combined intervention arms had significantly higher mortality (relative risk
      1.46, 95% CI 1.13 to 1.90, P = 0.004) than the control arm. The stopping rule for
      proof of benefit was not achieved, and the IDMC stopped the trial with a lower
      level of significance (P = 0.01) due to futility and an increased risk of
      mortality from bolus fluid expansion in children enrolled in the trial. The basis
      for this decision was that the local standard of care was not to use bolus fluid
      for the care of children with shock in these African countries, and this was a
      different standard of care to that used in the UK. These decisions emphasize two
      important principles: firstly, the IDMC should avoid inadvertent unblinding of
      the trial by commenting on amendments, and secondly, when considering stopping a
      trial, the IDMC should be guided by the local standard of care rather than
      standards of care in other parts of the world.

PMID- 23531380
TI  - Bronchopneumonia in wild boar (Sus scrofa) caused by Rhodococcus equi carrying
      the VapB type 8 plasmid.
AB  - BACKGROUND: Rhodococcus equi is associated with pyogranulomatous infections,
      especially in foals, and this bacterium has also emerged as a pathogen for
      humans, particularly immunocompromised patients. R. equi infections in pigs, wild
      boar (Sus scrofa) and humans are mainly due to strains carrying the intermediate
      virulence (VapB) plasmid. In Brazil, R. equi carrying the VapB type 8 plasmid is
      the most common type recovered from humans co-infected with the human
      immunodeficiency virus (HIV). R. equi infection in pigs and wild boar is
      restricted predominantly to the lymphatic system, without any reports of
      pulmonary manifestations. FINDINGS: This report describes the microbiological and
      histopathological findings, and molecular characterization of R. equi in two
      bronchopneumonia cases in wild boar using PCR and plasmid profile analysis by
      digestion with restriction endonucleases. The histological findings were
      suggestive of pyogranulomatous infection, and the plasmid profile of both R. equi
      isolates enabled the characterization of the strains as VapB type 8. CONCLUSIONS:
      This is the first report of bronchopneumonia in wild boar due to R. equi. The
      detection of the VapB type 8 plasmid in R. equi isolates emphasize that wild boar
      may be a potential source of pathogenic R. equi strains for humans.

PMID- 23531381
TI  - Maskless and low-destructive nanofabrication on quartz by friction-induced
      selective etching.
AB  - A low-destructive friction-induced nanofabrication method is proposed to produce
      three-dimensional nanostructures on a quartz surface. Without any template,
      nanofabrication can be achieved by low-destructive scanning on a target area and
      post-etching in a KOH solution. Various nanostructures, such as slopes,
      hierarchical stages and chessboard-like patterns, can be fabricated on the quartz
      surface. Although the rise of etching temperature can improve fabrication
      efficiency, fabrication depth is dependent only upon contact pressure and
      scanning cycles. With the increase of contact pressure during scanning, selective
      etching thickness of the scanned area increases from 0 to 2.9 nm before the yield
      of the quartz surface and then tends to stabilise after the appearance of a wear.
      Refabrication on existing nanostructures can be realised to produce deeper
      structures on the quartz surface. Based on Arrhenius fitting of the etching rate
      and transmission electron microscopy characterization of the nanostructure,
      fabrication mechanism could be attributed to the selective etching of the
      friction-induced amorphous layer on the quartz surface. As a maskless and low
      destructive technique, the proposed friction-induced method will open up new
      possibilities for further nanofabrication.

PMID- 23531382
TI  - Effects of red blood cell transfusion on hemodynamic parameters: a prospective
      study in intensive care unit patients.
AB  - BACKGROUND: The aim of the study was to investigate the effect of red blood cell
      (RBC) transfusion on hemodynamic parameters including transpulmonary
      thermodilution (TPTD)-derived variables. METHODS: We compared hemodynamic
      parameters obtained before and after RBC transfusion (2 RBC units) in 34
      intensive care unit (ICU) patients. RESULTS: Directly after RBC transfusion, we
      observed a significant increase in hematocrit (28 +/- 3 vs. 22 +/- 2%, p <
      0.001), hemoglobin (9.4 +/- 0.9 vs. 7.6 +/- 0.8 g/dL, p < 0.001), arterial oxygen
      content (CaO2) (12.2 +/- 1.2 vs. 9.9 +/- 1.0 mL/dL, p < 0.001), and oxygen
      delivery (DO2) (1073 +/- 369 vs. 934 +/- 288 mL/min, p < 0.001) compared with
      baseline. Cardiac output (CO) (8.89 +/- 3.06 vs. 9.42 +/- 2.75 L/min, p = 0.020),
      cardiac index (CI) (4.53 +/- 1.36 vs. 4.82 +/- 1.21 L/min/m2, p = 0.016), and
      heart rate (91 +/- 16 vs. 95 +/- 14 bpm, p = 0.007) were significantly lower
      following RBC transfusion while no significant change in stroke volume (SV) was
      observed. Mean arterial pressure (MAP) (median 87 vs. 78 mmHg, p < 0.001) and
      systemic vascular resistance index (SVRI) (median 1212 vs. 1103 dyn*s*cm-5*m2, p
      = 0.001) significantly increased directly after RBC transfusion. Global end
      diastolic volume index (GEDVI), extravascular lung water index (EVLWI), and
      pulmonary vascular permeability index (PVPI) did not significantly change.
      CONCLUSIONS: In ICU patients, the transfusion of 2 RBC units induces a
      significant decrease in CO and CI because of a significant decrease in heart rate
      (while SV remains unchanged). Despite the decrease in CO, DO2 significantly
      increases because of a significant increase in CaO2. In addition, RBC transfusion
      results in a significant increase in MAP and SVRI. No significant changes in TPTD
      parameters reflecting cardiac preload (GEDVI), pulmonary edema (EVLWI), and
      pulmonary vascular permeability (PVPI) are observed following RBC transfusion.

PMID- 23531383
TI  - Effect of dietary laminarin and fucoidan on selected microbiota, intestinal
      morphology and immune status of the newly weaned pig.
AB  - A 2 * 2 factorial experiment was conducted to investigate the interactions
      between laminarin (LAM; 0 and 300 parts per million (ppm)) and fucoidan (FUC; 0
      and 240 ppm) levels on intestinal morphology, selected microbiota and
      inflammatory cytokine gene expression in the weaned pig. There was an interaction
      between LAM and FUC supplementation on the Enterobacteriaceae population (P<
      0.05) and the abundance of attaching and effacing Escherichia coli (AEEC) strains
      (P< 0.05) in the colon. Pigs offered the FUC diet had a reduced
      Enterobacteriaceae population compared with pigs offered the basal diet. However,
      the effect of FUC on the Enterobacteriaceae population was not observed when
      combined with LAM. Pigs offered the LAM diet had reduced abundance of AEEC
      strains compared with pigs offered the basal diet. However, there was no effect
      of LAM on the abundance of AEEC strains when combined with FUC. There was an
      interaction between LAM and FUC supplementation on villous height (P< 0.01) and
      the villous height:crypt depth ratio (P< 0.01) in the duodenum. Pigs offered the
      LAM or FUC diet had an increased villous height and villous height:crypt depth
      ratio compared with pigs offered the basal diet. However, there was no effect of
      the LAM and FUC combination diet on intestinal morphology. Pigs offered the LAM
      supplemented diets had a lower IL-6 (P< 0.05), IL-17A (P< 0.01) and IL-1beta (P<
      0.01) mRNA expression in the colon compared with pigs offered the diets without
      LAM. In conclusion, supplementation with either LAM or FUC alone modified
      intestinal morphology and selected intestinal microbiota, but these effects were
      lost when offered in combination.

PMID- 23531384
TI  - Tuberculosis 2013 series.

PMID- 23531385
TI  - Zero deaths from tuberculosis: progress, reality, and hope.

PMID- 23531386
TI  - Progress and challenges in childhood tuberculosis.

PMID- 23531387
TI  - Alimuddin Zumla: infectious diseases guru and survivor.

PMID- 23531389
TI  - Tuberculosis biomarkers discovery: developments, needs, and challenges.
AB  - Biomarkers are indispensable to the development of new tuberculosis therapeutics
      and vaccines. The most robust biomarkers measure factors that are essential to
      the underlying pathological process of the disease being treated, and thus can
      capture the full effects of many types of interventions on clinical outcomes in
      multiple prospective, randomised clinical trials. Many Mycobacterium tuberculosis
      and human biomarkers have been studied over the past decade. Present research
      focuses on three areas: biomarkers predicting treatment efficacy and cure of
      active tuberculosis, the reactivation of latent tuberculosis infection, and the
      induction of protective immune responses by vaccination. Many older, non-specific
      markers of inflammation, when considered in isolation, do not have sufficient
      predictive values for clinical use in tuberculosis. Although no new accurate,
      tuberculosis-specific biomarkers have yet been discovered, substantial progress
      has been made in some areas. However, the qualification of biomarkers as a
      surrogate for a clinical endpoint in tuberculosis is very challenging, and, for
      biomarkers that are non-culture-based, impossible to pursue without the
      availability of well characterised biobanks containing biospecimens from patients
      who have had adequate follow-up to establish long-term treatment outcome. We
      review progress in tuberculosis biomarker development and efforts being made to
      harness resources to meet future challenges.

PMID- 23531390
TI  - Engaging communities in tuberculosis research.
AB  - According to a growing consensus among biomedical researchers, community
      engagement can improve the ethics and outcomes of clinical trials. Although
      successful efforts to develop community engagement practices in HIV/AIDS research
      have been reported, little attention has been given to engagement with the
      community in tuberculosis research. This article aims to draw attention to some
      existing community engagement initiatives in tuberculosis research and to
      resources that might help tuberculosis researchers to establish and implement
      community engagement programmes for their trials. One of these resources-the good
      participatory practice guidelines for tuberculosis drug trials-offers a
      conceptual framework and practical guidance for community engagement in
      tuberculosis research. To build momentum and to improve community engagement,
      lessons need to be shared, and formal assessment strategies for community
      engagement initiatives need to be developed. To build successfully on the
      promising activities described in this personal view, research funders and
      sponsors should show leadership in allocation of resources for the implementation
      and assessment of community engagement programmes in tuberculosis trials.

PMID- 23531388
TI  - Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future
      prospects for a point-of-care test.
AB  - Rapid progress has been made in the development of new diagnostic assays for
      tuberculosis in recent years. New technologies have been developed and assessed,
      and are now being implemented. The Xpert MTB/RIF assay, which enables
      simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF)
      resistance, was endorsed by WHO in December, 2010. This assay was specifically
      recommended for use as the initial diagnostic test for suspected drug-resistant
      or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries
      with a high tuberculosis burden and half of countries with a high multidrug
      resistant tuberculosis burden had incorporated the assay into their national
      tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF
      assay is undoubtedly a landmark event, clinical and programmatic effects and cost
      effectiveness remain to be defined. We review the rapidly growing body of
      scientific literature and discuss the advantages and challenges of using the
      Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other
      prospects within the developmental pipeline. A rapid, accurate point-of-care
      diagnostic test that is affordable and can be readily implemented is urgently
      needed. Investment in the tuberculosis diagnostics pipeline should remain a major
      priority for funders and researchers.

PMID- 23531391
TI  - Drug-resistant tuberculosis: time for visionary political leadership.
AB  - Two decades ago, WHO declared tuberculosis a global emergency, and invested in
      the highly cost-effective directly observed treatment short-course programme to
      control the epidemic. At that time, most strains of Mycobacterium tuberculosis
      were susceptible to first-line tuberculosis drugs, and drug resistance was not a
      major issue. However, in 2013, tuberculosis remains a major public health concern
      worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO
      estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great
      variation in the frequency of MDR tuberculosis between countries. In the past 8
      years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been
      reported in 84 countries, heralding the possibility of virtually untreatable
      tuberculosis. Increased population movement, the continuing HIV pandemic, and the
      rise in MDR tuberculosis pose formidable challenges to the global control of
      tuberculosis. We provide an overview of the global burden of drug-resistant
      disease; discuss the social, health service, management, and control issues that
      fuel and sustain the epidemic; and suggest specific recommendations for important
      next steps. Visionary political leadership is needed to curb the rise of MDR and
      XDR tuberculosis worldwide, through sustained funding and the implementation of
      global and regional action plans.

PMID- 23531392
TI  - Tuberculosis comorbidity with communicable and non-communicable diseases:
      integrating health services and control efforts.
AB  - Recent data for the global burden of disease reflect major demographic and
      lifestyle changes, leading to a rise in non-communicable diseases. Most countries
      with high levels of tuberculosis face a large comorbidity burden from both non
      communicable and communicable diseases. Traditional disease-specific approaches
      typically fail to recognise common features and potential synergies in
      integration of care, management, and control of non-communicable and communicable
      diseases. In resource-limited countries, the need to tackle a broader range of
      overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as
      global emergencies. The lethal interaction between tuberculosis and HIV
      coinfection in adults, children, and pregnant women in sub-Saharan Africa
      exemplifies the need for well integrated approaches to disease management and
      control. Furthermore, links between diabetes mellitus, smoking, alcoholism,
      chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and
      tuberculosis are well recognised. Here, we focus on interactions, synergies, and
      challenges of integration of tuberculosis care with management strategies for non
      communicable and communicable diseases without eroding the functionality of
      existing national programmes for tuberculosis. The need for sustained and
      increased funding for these initiatives is greater than ever and requires
      increased political and funder commitment.

PMID- 23531393
TI  - Alignment of new tuberculosis drug regimens and drug susceptibility testing: a
      framework for action.
AB  - New tuberculosis drug regimens are creating new priorities for drug
      susceptibility testing (DST) and surveillance. To minimise turnaround time, rapid
      DST will need to be prioritised, but developers of these assays will need better
      data about the molecular mechanisms of resistance. Efforts are underway to link
      mutations with drug resistance and to develop strain collections to enable
      assessment of new diagnostic assays. In resource-limited settings, DST might not
      be appropriate for all patients with tuberculosis. Surveillance data and
      modelling will help country stakeholders to design appropriate DST algorithms and
      to decide whether to change drug regimens. Finally, development of practical DST
      assays is needed so that, in countries where surveillance and modelling show that
      DST is advisable, these assays can be used to guide clinical decisions for
      individual patients. If combined judiciously during both development and
      implementation, new tuberculosis regimens and new DST assays have enormous
      potential to improve patient outcomes and reduce the burden of disease.

PMID- 23531394
TI  - TEG(r) and ROTEM(r) in trauma: similar test but different results?
AB  - INTRODUCTION: Transfusion in trauma is often empiric or based on traditional lab
      tests. Viscoelastic tests such as thromboelastography (TEG(r)) and rotational
      thromboelastometry (ROTEM(r)) have been proposed as superior to traditional lab
      tests. Due to the similarities between the two tests, general opinion seems to
      consider them equivalent with interchangeable interpretations. However, it is not
      clear whether the results can be similarly interpreted. This review evaluates the
      comparability between TEG and ROTEM and performs a descriptive review of the
      parameters utilized in each test in adult trauma patients. METHODS: PUBMED
      database was reviewed using the keywords "thromboelastography" and "compare",
      between 2000 and 2011. Original studies directly comparing TEG(r) with ROTEM(r)
      in any area were retrieved. To verify the individual test parameter used in
      studies involving trauma patients, we further performed a review using the
      keywords "thromboelastography" and "trauma" in the PUBMED database. RESULTS: Only
      4 studies directly compared TEG(r) with ROTEM(r). One in liver transplantation
      found that transfusion practice could differ depending on the device in use.
      Another in cardiac surgery concluded that all measurements are not completely
      interchangeable. The third article using commercially available plasma detected
      clinically significant differences in the results from the two devices. The
      fourth one was a head-to-head comparison of the technical aspects. The 24
      articles reporting the use of viscoelastic tests in trauma patients, presented
      considerable heterogeneity. CONCLUSION: Both tests are potentially useful as
      means to rapidly diagnose coagulopathy, guide transfusion and determine outcome
      in trauma patients. Differences in the activators utilized in each device limit
      the direct comparability. Standardization and robust clinical trials comparing
      the two technologies are needed before these tests can be widely recommended for
      clinical use in trauma.

PMID- 23531395
TI  - Analysis of HAX-1 gene expression in esophageal squamous cell carcinoma.
AB  - OBJECTIVE: To explore the expression of HAX-1 mRNA and protein in esophageal
      squamous cell carcinoma (ESCC) and its relation with the prognosis of patients
      with ESCC. METHODS: The expression of HAX-1 mRNA and protein were detected with
      quantitative real-time RT-PCR and immunohistochemical method in 112 ESCC samples
      and 112 corresponding non-neoplastic samples. Survival curves were made with
      follow-up data. The relations of the prognosis with clinical and pathological
      characteristics were analyzed. RESULTS: The expression level of HAX-1 mRNA and
      the strong positive rate of HAX-1 protein were significantly higher in ESCC
      samples (0.527 +/- 0.060 and 45.54%) than that in non-neoplastic samples (0.121
      +/- 0.017 and 0.00%), and in ESCC samples with lymph node metastasis (0.554 +/-
      0.054 and 71.11%) than that in ESCC samples without lymph node metastasis (0.509
      +/- 0.058 and 28.36%) (all P < 0.01). HAX-1 mRNA expression level was a risk
      factor of lymph node metastasis in patients with ESCC (P = 0.000). There were
      significant differences in survival curves between lymph node metastatic group
      and non-metastatic group (P = 0.000), and among groups of HAX-1 protein
      expression +, ++and +++(,P = 0.000); but no statistical significance between male
      patients and female patients (P = 0.119), and between >=60 years old patients and
      <60 years old patients (P = 0.705). The level of HAX-1 mRNA (P = 0.000) and
      protein (P = 0.005) were risk factors of survival, but lymph node metastasis (P =
      0.477) was not. CONCLUSION: There is HAX-1 over-expression in ESCC tissue and HAX
      1 mRNA level is a risk factor of lymph node metastasis. The level of HAX-1 mRNA
      and protein were risk factors of survival in patients with ESCC. HAX-1 may be a
      novel therapeutic target for ESCC treatment. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5130393079296037.

PMID- 23531400
TI  - The role of continuous glucose monitoring in the care of children with type 1
      diabetes.
AB  - Continuous glucose monitoring (CGM), while a relatively new technology, has the
      potential to transform care for children with type 1 diabetes. Some, but not all
      studies, have shown that CGM can significantly improve hemoglobin A1c levels and
      reduce time spent in the hypoglycemic range in children, particularly when used
      as part of sensor-augmented pump (SAP) therapy. Despite the publication of recent
      clinical practice guidelines suggesting CGM be offered to all children 8 years of
      age or older who are likely to benefit, and studies showing that younger children
      can also benefit, this technology is not yet commonly used by children with type
      1 diabetes. Effects of CGM are enhanced when used on a near-daily basis (a use
      dependent effect) and with insulin pump therapy. Therefore, coordinated
      strategies are needed to help children and their families initiate and continue
      to use this resource for diabetes care. This review introduces CGM to pediatric
      endocrinologists who are not yet familiar with the finer details of this
      technology, summarizes current data showing the benefits and limitations of CGM
      use in children, reviews specific case examples demonstrating when CGM can be
      helpful, and shows the value of both retrospective and real-time CGM. It is hoped
      that this information leads to discussion of this technology in pediatric
      endocrinology clinics as an important next step in improving the care of children
      with type 1 diabetes.

PMID- 23531401
TI  - A pilot study to determine the feasibility of collecting amniotic fluid samples
      from women during labour and measuring amniotic fluid lactate at point of care.
AB  - BACKGROUND: The level of lactate in amniotic fluid may provide useful clinical
      information when assessing progress of a woman's labour and if so, a rapid,
      reliable method to assess amniotic fluid lactate is required in order to be
      clinically relevant. However, measuring lactate levels in amniotic fluid, using
      portable, handheld lactate meters may be less accurate than reference laboratory
      instruments designed to measure lactate levels in aqueous solutions. Prior to
      conducting a large study, we assessed recruitment, consent and sampling
      procedures, and the accuracy of a handheld lactate meter to measure lactate in
      amniotic fluid. We compared amniotic fluid lactate results obtained using the
      hand held Lactate Pro (Arkray) to results obtained using reference laboratory
      methods ABX Pentra 400 (Horiba). RESULTS: We recruited 35 nulliparous women
      during their antenatal hospital visits and tested amniotic fluid samples
      collected from 20 labouring women. The handheld Lactate Pro meter was found
      accurate from 9-20 mmol/L with a Passing & Bablok regression of y = 0.18 + 0.97x
      (95% CI 0.76-1.45). Amniotic fluid lactate results remained reliable in the
      presence of potential contaminants commonly encountered during labour; obstetric
      lubricant, blood and meconium. CONCLUSION: The measurement of amniotic fluid
      lactate using the Lactate Pro meter was reliable compared to reference laboratory
      methods for measuring lactate levels in amniotic fluid. The pilot study enabled
      the refinement of information, recruitment, consenting and sampling procedures
      prior to commencing a large cohort study.

PMID- 23531402
TI  - ACS network-based implementation of therapeutic hypothermia for the treatment of
      comatose out-of-hospital cardiac arrest survivors improves clinical outcomes: the
      first European experience.
AB  - BACKGROUND: There is a paucity of data regarding clinical outcomes associated
      with the integration of a mild therapeutic hypothermia (MTH) protocol into a
      regional network dedicated to treatment of patients with acute coronary syndromes
      (ACS). Additionally, a recent report suggests that the neurological benefits of
      MTH therapy in interventionally managed ACS patients resuscitated from out-of
      hospital cardiac arrest (OHCA) may be potentially offset by the catastrophic
      occurrence of stent thrombosis. The goal of this study was to share our
      experience with the implementation of an MTH program using a previously
      established ACS network in consecutive comatose OHCA survivors undergoing
      interventional management due to an initial diagnosis of ACS and to assess the
      clinical effectiveness and safety of MTH. METHODS: We conducted a retrospective
      historically controlled single centre study. Hospital survival with a favourable
      neurological outcome (Cerebral Performance Category of 1 or 2) and all-cause in
      hospital mortality were the primary and secondary efficacy end points,
      respectively. Occurrence of definite stent thrombosis was the primary safety end
      point while the development of pneumonia, presence of positive blood cultures,
      occurrence of probable stent thrombosis, any bleeding complications, need for red
      blood cell transfusion and presence of rhythm and conductions disorders during
      hospitalisation constituted secondary safety end points. RESULTS: Comatose OHCA
      survivors (n = 32) were referred to our Department based on ECG recording
      transmissions and/or phone consultations or admitted from the Emergency
      Department. Compared with controls (n = 33), they were significantly more likely
      to be discharged from hospital with a favourable neurological outcome (59 vs.
      27%; p < 0.05; number needed to treat [NNT] = 3.11) and experienced lower all
      cause in-hospital mortality (13 vs. 55%; p < 0.05; NNT = 2.38). Rates of all
      safety end points were similar in patients treated with and without MTH.
      CONCLUSIONS: Our study indicates that a regional system of care for OHCA
      survivors may be successfully implemented based on an ACS network, leading to an
      improvement in neurological status and to a reduction of in-hospital mortality in
      patients treated with MTH, without any excess of complications. However, our
      findings should be verified in large, prospective trials.

PMID- 23531403
TI  - Lipid profile components and incident cerebrovascular events versus coronary
      heart disease; the result of 9 years follow-up in Tehran Lipid and Glucose Study.
AB  - OBJECTIVE: To assess the effects of lipid component total cholesterol (TC),
      triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C) and non-HDL-C on risk of stroke events versus
      coronary heart disease (CHD). METHODS: The study was conducted on 2620 Iranians,
      aged >= 50 years, free from cardiovascular events at baseline (1999-2001). The
      multivariable hazard ratios (HRs) for stroke/CHD were calculated for 1 mmol/L
      change in lipid components, using Cox proportional hazard regression. RESULTS:
      During 9.1 years of follow-up, 73 and 358 cases of stroke and CHD occurred. We
      found significant interactions between TC and non-HDL-C with gender in risk
      prediction of stroke. Among women, multivariate adjusted HRs of ischemic stroke
      were 1.40 (1.08-1.82), 1.66 (0.71-3.86), 2.27 (0.58-8.91), 1.51 (1.06-2.15) and
      1.36 (1.024-1.78) for TC, Ln TG, HDL-C, LDL-C and non-HDL-C respectively, while
      corresponding HRs of ischemic stroke for men were 0.78 (0.55-1.11), 0.71 (0.33
      1.51), 1.04 (0.24-4.47), 0.82 (0.56-1.22), 0.78 (0.55-1.11), respectively. We
      found no interaction between gender and any of the lipids in risk prediction of
      incident CHD (p > 0.3). All lipid components were independently associated with
      CHD in whole population. CONCLUSION: The associations of lipid components on
      ischemic stroke were modified by gender. Only among female population, TC, LDL-C
      and non-HDL-C were independently associated with increased risk of ischemic
      stroke. Regarding CHD events, all lipid components were significant predictors.

PMID- 23531404
TI  - Association of genetic polymorphisms of RANK, RANKL and OPG with bone mineral
      density in Chinese peri- and postmenopausal women.
AB  - OBJECTIVES: To explore the influence of 14 single nucleotide polymorphisms (SNPs)
      in receptor activator of nuclear factor-kappa B (RANK), RANK ligand (RANKL) and
      osteoprotegerin (OPG) on bone mineral density (BMD) in a Chinese female
      population. DESIGN AND METHODS: A cross-sectional study was conducted in 108
      perimenopausal and 127 postmenopausal women aged 43-65 years. All participants
      underwent lumbar spinal and nondominant femoral BMD evaluation by dual energy X
      ray absorptiometry. Fourteen RANK, RANKL and OPG genotypes were determined by
      chip-based MALDI-TOF mass spectrometry. The differences between the BMDs of the
      RANK genotypes were analyzed. RESULTS: Five SNPs (rs6993813, rs4355801, rs1032129
      and rs2073618 in OPG and rs3018362 in RANK) were significantly associated with
      BMD or with BMD adjusted for body weight or years since menopause, mostly at the
      femoral neck but also partly at the total hip (p<0.05). The risk allele
      frequencies observed in our sample were different from those found in Europeans
      but the effects of these risk alleles on BMD values had the same direction in our
      cohort as in Europeans, except for rs3018362 with G as the risk allele, which was
      contrary to other studies. None of the SNPs in RANKL were associated with BMD at
      any anatomical site. CONCLUSIONS: Our findings suggest that OPG and RANK but not
      RANKL genetic polymorphisms influence BMD mainly in the femoral neck in peri- and
      postmenopausal Chinese women. This contributes to the understanding of the role
      of genetic variation in this pathway in determining bone health.

PMID- 23531405
TI  - Validation of various adaptive threshold methods of segmentation applied to
      follicular lymphoma digital images stained with 3,3'
      Diaminobenzidine&Haematoxylin.
AB  - The comparative study of the results of various segmentation methods for the
      digital images of the follicular lymphoma cancer tissue section is described in
      this paper. The sensitivity and specificity and some other parameters of the
      following adaptive threshold methods of segmentation: the Niblack method, the
      Sauvola method, the White method, the Bernsen method, the Yasuda method and the
      Palumbo method, are calculated. Methods are applied to three types of images
      constructed by extraction of the brown colour information from the artificial
      images synthesized based on counterpart experimentally captured images. This
      paper presents usefulness of the microscopic image synthesis method in evaluation
      as well as comparison of the image processing results. The results of thoughtful
      analysis of broad range of adaptive threshold methods applied to: (1) the blue
      channel of RGB, (2) the brown colour extracted by deconvolution and (3) the
      'brown component' extracted from RGB allows to select some pairs: method and type
      of image for which this method is most efficient considering various criteria
      e.g. accuracy and precision in area detection or accuracy in number of objects
      detection and so on. The comparison shows that the White, the Bernsen and the
      Sauvola methods results are better than the results of the rest of the methods
      for all types of monochromatic images. All three methods segments the
      immunopositive nuclei with the mean accuracy of 0.9952, 0.9942 and 0.9944
      respectively, when treated totally. However the best results are achieved for
      monochromatic image in which intensity shows brown colour map constructed by
      colour deconvolution algorithm. The specificity in the cases of the Bernsen and
      the White methods is 1 and sensitivities are: 0.74 for White and 0.91 for Bernsen
      methods while the Sauvola method achieves sensitivity value of 0.74 and the
      specificity value of 0.99. According to Bland-Altman plot the Sauvola method
      selected objects are segmented without undercutting the area for true positive
      objects but with extra false positive objects. The Sauvola and the Bernsen
      methods gives complementary results what will be exploited when the new method of
      virtual tissue slides segmentation be develop. VIRTUAL SLIDES: The virtual slides
      for this article can be found here: slide 1:
      http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=13617947952
      77 and slide 2:
      http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=13617948230
      17.

PMID- 23531406
TI  - Response to Esposito et al.

PMID- 23531407
TI  - Total urogenital mobilization by posterior sagittal approach and ileal
      neovaginoplasty in cloacal repair by a common channel of 4 cm.
AB  - OBJECTIVE: The total urogenital mobilization (TUM) technique avoids dissection of
      the vagina from the urinary tract. However, in the case of a long common channel,
      bowel interposition for vaginal replacement may be necessary. We present a video
      of the TUM technique in cloacal repair with ileal neovaginoplasty. METHODS: An 8
      month-old female patient with cloaca, presenting a 4-cm common channel, was
      operated on by the TUM technique, through a perineal sagittal with additional
      abdominal approach. She had undergone decompressing colostomy at birth. Total
      urogenital sinus mobilization was performed with ileal neovaginoplasty. RESULTS:
      The patient had a good postoperative outcome, an endoscopy of all structures
      reconstructed was performed at PO day 30, and home dilatation of colon and vagina
      by parents was initiated. CONCLUSION: TUM with neovaginoplasty bowel
      interposition is an effective technique for repairing long common channels.

PMID- 23531408
TI  - Enhancing trauma education worldwide through telemedicine.
AB  - Advances in information and communication technologies are changing the delivery
      of trauma care and education. Telemedicine is a tool that can be used to deliver
      expert trauma care and education anywhere in the world. Trauma is a rapidly
      evolving field requiring access to readily available sources of information.
      Through videoconferencing, physicians can participate in continuing education
      activities such as Grand Rounds, seminars, conferences and journal clubs.
      Exemplary programs have shown promising outcomes of teleconferences such as
      enhanced learning, professional collaborations, and networking. This review
      introduces the concept of telemedicine for trauma education, and highlights
      efforts of programs that are utilizing telemedicine to unite institutions across
      the world.

PMID- 23531409
TI  - Copy-number variation of cancer-gene orthologs is sufficient to induce cancer
      like symptoms in Saccharomyces cerevisiae.
AB  - BACKGROUND: Copy-number variation (CNV), rather than complete loss of gene
      function, is increasingly implicated in human disease. Moreover, gene dosage is
      recognised as important in tumourigenesis, and there is an increasing realisation
      that CNVs may not be just symptomatic of the cancerous state but may, in fact, be
      causative. However, the identification of CNV-related phenotypes for mammalian
      genes is a slow process, due to the technical difficulty of constructing deletion
      mutants. Using the genome-wide deletion library for the model eukaryote,
      Saccharomyces cerevisiae, we have identified genes (termed haploproficient, HP)
      which, when one copy is deleted from a diploid cell, result in an increased rate
      of proliferation. Since haploproficiency under nutrient-sufficient conditions is
      a novel phenotype, we sought here to characterise a subset of the yeast
      haploproficient genes which seem particularly relevant to human cancers. RESULTS:
      We show that, for a subset of HP genes, heterozygous deletion is sufficient to
      cause aberrant cell cycling and altered rates of apoptosis, phenotypes associated
      with cancer in mammalian cells. A majority of these yeast genes are the orthologs
      of mammalian cancer genes, and hence our studies suggest that CNV of these
      oncogenic orthologs may be sufficient to lead to tumourigenesis in human cells.
      Moreover, where not already implicated, this cluster of cancer-like phenotypes in
      this model eukaryote may be predictive of the involvement in cancer of the
      mammalian orthologs of these yeast HP genes. Using the yeast set as a model, we
      show that the response to a range of anti-cancer drugs is strongly dependent on
      gene dosage, such that intermediate concentrations of the drugs can actually
      increase a mutant's growth rate. CONCLUSIONS: The exploitation of data on the
      phenotypic impact of heterozygosis in Saccharomyces cerevisiae has permitted the
      prediction of CNVs affecting tumourigenesis in humans. Our yeast data also
      suggest that the identification of CNVs in tumour cells may assist both the
      selection of anti-cancer drugs and the dosages at which they should be
      administered if they are to be a beneficial, rather than a deleterious, therapy.

PMID- 23531411
TI  - MacroH2A--an epigenetic regulator of cancer.
AB  - Epigenetic regulation is one of the most promising and expanding areas of cancer
      research. One of the emerging, but least understood aspects of epigenetics is the
      facultative and locus-specific incorporation of histone variants and their
      function in chromatin. With the characterization of the first loss of function
      phenotypes of the macroH2A histone variants, previously unrecognized epigenetic
      mechanisms have now moved into the spotlight of cancer research. Here, we
      summarize data supporting different molecular mechanisms that could mediate the
      primarily tumor suppressive function of macroH2A. We further discuss context
      dependent and isoform-specific functions. The aim of this review is to provide
      guidance for those assessing macroH2A's potential as biomarker or therapeutic
      intervention point. 

PMID- 23531410
TI  - Molars and incisors: show your microarray IDs.
AB  - BACKGROUND: One of the key questions in developmental biology is how, from a
      relatively small number of conserved signaling pathways, is it possible to
      generate organs displaying a wide range of shapes, tissue organization, and
      function. The dentition and its distinct specific tooth types represent a
      valuable system to address the issues of differential molecular signatures. To
      identify such signatures, we performed a comparative transcriptomic analysis of
      developing murine lower incisors, mandibular molars and maxillary molars at the
      developmental cap stage (E14.5). RESULTS: 231 genes were identified as being
      differentially expressed between mandibular incisors and molars, with a fold
      change higher than 2 and a false discovery rate lower than 0.1, whereas only 96
      genes were discovered as being differentially expressed between mandibular and
      maxillary molars. Numerous genes belonging to specific signaling pathways (the
      Hedgehog, Notch, Wnt, FGF, TGFbeta/BMP, and retinoic acid pathways), and/or to
      the homeobox gene superfamily, were also uncovered when a less stringent fold
      change threshold was used. Differential expressions for 10 out of 12 (mandibular
      incisors versus molars) and 9 out of 10 selected genes were confirmed by
      quantitative reverse transcription-PCR (qRT-PCR). A bioinformatics tool
      (Ingenuity Pathway Analysis) used to analyze biological functions and pathways on
      the group of incisor versus molar differentially expressed genes revealed that
      143 genes belonged to 9 networks with intermolecular connections. Networks with
      the highest significance scores were centered on the TNF/NFkappaB complex and the
      ERK1/2 kinases. Two networks ERK1/2 kinases and tretinoin were involved in
      differential molar morphogenesis. CONCLUSION: These data allowed us to build
      several regulatory networks that may distinguish incisor versus molar identity,
      and may be useful for further investigations of these tooth-specific ontogenetic
      programs. These programs may be dysregulated in transgenic animal models and
      related human diseases leading to dental anomalies.

PMID- 23531412
TI  - Organizer formation in Hydra is disrupted by thalidomide treatment.
AB  - Thalidomide is a drug that is well known for its teratogenic properties in
      humans. Surprisingly, thalidomide does not have teratogenic effects on mouse
      development. We investigated the effect of thalidomide on patterning in hydra, an
      early metazoan with a very simple axial symmetry. Hydra develops asexually via
      Wnt-dependent organizer formation, leading to the budding of a new organism. We
      observe both induction and inhibition of organizer formation depending on
      cellular context. Interestingly, thalidomide treatment altered budding and the
      developing organizer, but had little effect on the adult. Expression of Hybra1, a
      marker of the organizer increased upon thalidomide treatment. However when the
      organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition,
      thalidomide suppresses induction. We show that inhibition of Wnt signaling is not
      mediated by induction of the BMP pathway. We show that thalidomide activity on
      organizer formation in hydra depends on the activity of casein kinase1 and the
      abundance of beta-catenin. Finally, we find that interstitial cells, multipotent
      cells which give rise to nemoatocytes, neural, digestive and germline cells, are
      partially responsible for the inhibitory effect of thalidomide.

PMID- 23531414
TI  - 8th German Conference on Chemoinformatics: 26 CIC-Workshop Goslar, Germany. 11-13
      November 2012. Abstracts.

PMID- 23531413
TI  - Paranoia and post-traumatic stress disorder in the months after a physical
      assault: a longitudinal study examining shared and differential predictors.
AB  - BACKGROUND: Being physically assaulted is known to increase the risk of the
      occurrence of post-traumatic stress disorder (PTSD) symptoms but it may also skew
      judgements about the intentions of other people. The objectives of the study were
      to assess paranoia and PTSD after an assault and to test whether theory-derived
      cognitive factors predicted the persistence of these problems. METHOD: At 4 weeks
      after hospital attendance due to an assault, 106 people were assessed on multiple
      symptom measures (including virtual reality) and cognitive factors from models of
      paranoia and PTSD. The symptom measures were repeated 3 and 6 months later.
      RESULTS: Factor analysis indicated that paranoia and PTSD were distinct
      experiences, though positively correlated. At 4 weeks, 33% of participants met
      diagnostic criteria for PTSD, falling to 16% at follow-up. Of the group at the
      first assessment, 80% reported that since the assault they were excessively
      fearful of other people, which over time fell to 66%. Almost all the cognitive
      factors (including information-processing style during the trauma, mental defeat,
      qualities of unwanted memories, self-blame, negative thoughts about self, worry,
      safety behaviours, anomalous internal experiences and cognitive inflexibility)
      predicted later paranoia and PTSD, but there was little evidence of differential
      prediction. CONCLUSIONS: Paranoia after an assault may be common and
      distinguishable from PTSD but predicted by a strikingly similar range of factors.

PMID- 23531415
TI  - Anal phyllodes tumor in a male patient: a unique case presentation and literature
      review.
AB  - Lesions of anogenital mammary-like glands are rare, and only 44 female cases have
      been reported. Herein, we describe a particularly rare case of phyllodes tumor of
      anogenital mammary-like glands in a 41-year-old male presenting anal bleeding.
      Papillectomy was performed. The excised tumor was circumscribed in shape, and
      after it was sliced into sections, it was noted that there were leaf-like slits
      on the surface of cut side. Under the microscope, the tumor was found to be
      biphasic, with a bland glandular epithelium and low-to-intermediate cellular
      stroma, which together created the leaf-like slits. Gynecomastoid hyperplasia was
      evident at the periphery. The epithelium showed immuno-activity for ER,
      PR(focal), AR, and GCDFP-15. The stromal cells showed positive staining for CD34
      and vimentin. The morphology and immunophenotype were similar to benign phyllodes
      tumors of breast. To the best of our knowledge, this case report represents the
      first case of phyllodes tumor of anogenital mammary-like glands with
      gynecomastoid hyperplasia at the periphery in a male patient. To make a
      diagnosis, we had to differentiate this lesion from hidradenoma papilliferum of
      skin appendage, phyllodes tumor of ectopic prostatic tissue, and other tumors of
      anogenital mammary-like glands analogous to the breast tumor (e.g., fibroadenoma
      phyllodes, periductal stromal sarcoma, and spindle cell carcinoma). While
      gynecomastia of male breast is usually a result of hormone imbalance, our
      patient's tumor did not seem to be related to peripheral hormone status in the
      anogenital mammary-like glands. Nevertheless, because hormone imbalance has been
      strongly related to male breast cancer, hormone levels may need to be followed in
      male patients who have this rare malady. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1509145815899177.

PMID- 23531417
TI  - Comparing impedance cardiography and echocardiography in the assessment of
      reduced left ventricular systolic function.
AB  - BACKGROUND: An early and accurate diagnosis of chronic heart failure is a big
      challenge for a general practitioner. Assessment of left ventricular function is
      essential for the diagnosis of heart failure and the prognosis. A gold standard
      for identifying left ventricular function is echocardiography. Echocardiography
      requires input from specialized care and has a limited access in Swedish primary
      health care. Impedance cardiography (ICG) is a noninvasive and low-cost method of
      examination. The survey technique is simple and ICG measurement can be performed
      by a general practitioner. ICG has been suggested for assessment of left
      ventricular function in patients with heart failure. We aimed to study the
      association between hemodynamic parameters measured by ICG and the value of
      ejection fraction as a determinant of reduced left ventricular systolic function
      in echocardiography. METHODS: A non-interventional, observational study conducted
      in the outpatients heart failure unit. Thirty-six patients with the diagnosis of
      chronic heart failure were simultaneously examined by echocardiography and ICG.
      Distribution of categorical variables was presented as numbers. Distribution of
      continuous variables was presented as a mean and 95% Confidence Interval. Kruskal
      Wallis test was used to compare variables and show differences between the
      groups. A p-value of <0.05 was considered significant. RESULTS: We found that
      three ICG parameters: pre-ejection fraction, left ventricular ejection time and
      systolic time ratio were significantly associated with ejection fraction measured
      by echocardiography. CONCLUSIONS: The association which we found between EF and
      ICG parameters was not reported in previous studies. We found no association
      between EF and ICG parameters which were suggested previously as the determinants
      of reduced left ventricular systolic function.The knowledge concerning
      explanation of hemodynamic parameters measured by ICG that is available nowadays
      is not sufficient to adopt the method in practice and use it to describe left
      ventricular systolic dysfunction.

PMID- 23531418
TI  - Nursing's crisis of care: what part does nursing education own?

PMID- 23531416
TI  - Using whole mount in situ hybridization to examine thyroid hormone deiodinase
      expression in embryonic and larval zebrafish: a tool for examining OH-BDE
      toxicity to early life stages.
AB  - Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites
      (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that
      have been shown to disrupt thyroid hormone regulation both in mammals and in
      fish. The purpose of this study was to determine the precise organ and tissue
      locations that express genes critical to thyroid hormone regulation in developing
      zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their
      expression. While RT-PCR can provide quantitative data on gene expression, it
      lacks spatial sensitivity to examine localized gene expression; and, isolation of
      organs from zebrafish embryos is technically difficult, if not impossible. For
      this reason, the present study used whole mount in situ hybridization to
      simultaneously localize and quantify gene expression in vivo. While PBDEs and OH
      BDEs have been shown to inhibit the activity and expression of deiodionases, a
      family of enzymes that regulate thyroid hormone concentrations intracellularly,
      it is unclear whether or not they can affect regional expression of the different
      isoforms during early development. In this study we investigated deiodinase 1
      (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the
      following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24,
      48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression
      of these genes that were highly localized. To demonstrate the use of this
      technique for investigating potential endocrine disrupting effects, zebrafish
      embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47. Significant increases in
      mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain
      and pronephric duct, respectively (quantified by measuring intensity of
      coloration using ImageJ analysis software) were observed, suggesting localized
      response at the HPT axis with the possibility of impacting neurodevelopment. Our
      results demonstrate effects of OH-BDEs on thyroid regulating gene expression and
      provide more insight into potential sites of injury during early life stages.

PMID- 23531419
TI  - Onconeuronal antigen Cdr2 correlates with HIF prolyl-4-hydroxylase PHD1 and worse
      prognosis in renal cell carcinoma.
AB  - Neoplastic expression of the onconeuronal cerebellar degeneration-related antigen
      Cdr2 in ovary and breast tumors is associated with paraneoplastic cerebellar
      degeneration (PCD). Cdr2 protein expression is normally restricted to neurons,
      but aberrant Cdr2 expression has mainly been described for breast and ovarian
      tumors. Previously, we found strong Cdr2 protein expression in the papillary
      subtype of renal cell carcinoma (pRCC) and showed that Cdr2 interacts with the
      hypoxia-inducible factor (HIF) prolyl-4-hydroxylase PHD1. High Cdr2 protein
      levels are associated with decreased HIF-dependent gene expression in cells as
      well as in clinical pRCC samples, providing a possible explanation why pRCCs are
      the most hypovascular renal tumors. Here, we demonstrate that strong Cdr2 protein
      expression in clinical samples from pRCC patients correlates with elevated PHD1
      protein levels, suggesting that increased PHD1 activity attenuates HIF-dependent
      gene expression. Interestingly, survival analysis revealed a significant
      correlation between high levels of Cdr2 expression and worse patient outcome in
      clear cell (cc) RCC patients. These findings provide evidence that Cdr2 might
      represent an important tumor antigen in kidney cancer and possibly in other
      cancer types as well. In contrast to ovary and breast tumor patients who develop
      PCD, no Cdr2 auto-antibodies were detected in the serum of pRCC patients, which
      is in line with the fact that pRCC patients have not been reported to display
      paraneoplastic neurodegenerative syndromes. This suggests that, despite a shared
      target antigen, tumor immunity and autoimmunity only partially overlap, and also
      highlights to which extent immuno-surveillance against cancer can be clinically
      silent.

PMID- 23531420
TI  - Restoration of chemosensitivity in cancer cells with MDR phenotype by
      deoxyribozyme, compared with ribozyme.
AB  - One of the main mechanisms for multidrug resistance (MDR) involves multidrug
      resistance gene 1 (MDR1) which encodes P-glycoprotein (Pgp). Pgp acts as a drug
      efflux pump and exports chemotherapeutic agents from cancer cells. Specific
      inhibition of Pgp expression by gene therapy is considered a well-respective
      strategy having less innate toxicities. At present, the investigation of DRz in
      reversal MDR is scarce. In the study, phosphorothioate DRz that targets to the
      translation initiation codon AUG was synthesized and transfected into breast
      cancer cells and leukemia cells with MDR phenotype. ASODN (antisense
      oligonucleotide) and ribozyme targets to the same region were also synthesized
      for comparison analysis. Alterations in MDR1 mRNA and Pgp were determined by RT
      PCR, Northern blot, flow cytometry and Rh123 retention tests. Chemosensitivity of
      the treated cells was determined by MTT assay. The results showed that DRz could
      significantly suppress expression of MDR1 mRNA and inhibit synthesis of Pgp. The
      efflux activity of Pgp was inhibited accordingly. Chemosensitivity assay showed
      that a 21-fold reduction in drug resistance for Adriamycin and a 45-fold
      reduction in drug resistance for Vinblastine were found in the treated cells 36h
      after transfection. These data suggest that DRz targeted to the translation
      initiation codon AUG can reverse MDR phenotype in cancer cells and restore their
      chemosensitivity. Moreover, the reversal efficiency of DRz is better than that of
      ribozyme and ASODN targets to the same region of MDR1 mRNA.

PMID- 23531421
TI  - Fatal motorcycle crashes: a serious public health problem in Brazil.
AB  - INTRODUCTION: The numbers of two-wheel vehicles are growing across the world. In
      comparison to other vehicles, motorcycles are cheaper and thus represent a
      significant part of the automobile market. Both the mobility and speed are
      attractive factors to those who want to use them for work or leisure. Crashes
      involving motorcyclists have become an important issue, especially fatal ones.
      Specific severe injuries are responsible for the deaths. Defining them is
      necessary in order to offer better prevention and a more suitable medical
      approach. METHODS: All fatal motorcycle crashes between January 2001 and December
      2009 in Campinas, Brazil, were analyzed in this study. Official data have been
      collected from police incident reports, hospitals' registers and autopsies. Both
      incidents and casualties were analyzed according to relevant variables. The
      Injury Severity Score (ISS) was calculated, describing the most potentially fatal
      injuries. RESULTS: There were 479 deaths; 90.8% were male; the mean age was 27.8
      (range 0-73); 86.4% were conductors of the vehicles; blood alcohol was positive
      in 42.3%; 49.7% died at a hospital; 32.6% died at the scene; 26.1% of the
      accidents occurred at night, 69.1% were urban and 30.9% occurred on highways. The
      main causes of injury were collisions (63%) and falls (14%). The mean ISS was
      38.5 (range 9-75). With regard to injuries, head trauma (67%) and thoracic trauma
      (40%) were the most common, followed by abdominal trauma (35%). Traumatic brain
      injury (67%) and hypovolemic shock (38%) were the most frequent causes of death.
      CONCLUSIONS: Alcohol was a significant factor in relation to the accidents. Head
      trauma was the most frequent and severe injury. Half of the victims died before
      receiving adequate medical attention, suggesting that prevention programs and
      laws should be implemented and applied in order to save future lives.

PMID- 23531422
TI  - Quantifying fibronectin adhesion with nanoscale spatial resolution on
      glycosaminoglycan doped polypyrrole using Atomic Force Microscopy.
AB  - BACKGROUND: The interaction of ECM proteins is critical in determining the
      performance of materials used in biomedical applications such as tissue
      regeneration, implantable bionics and biosensing. METHODS: To improve our
      understanding of ECM protein-conducting polymer interactions, we have used Atomic
      Force Microscopy (AFM) to elucidate the interactions of fibronectin (FN) on
      polypyrrole (PPy) doped with different glycosaminoglycans. RESULTS: We were able
      to classify four main types of FN interactions, including those related to 1) non
      specific adhesion, 2) protein unfolding and subsequent unbinding from the
      surface, 3) desorption and 4) interactions with no adhesion. FN adhesion on
      PPy/hyaluronic acid showed a significantly lower density of surface adhesion with
      the adhesion restricted to nodule structures, as opposed to their peripheries, of
      the polymer morphology. In contrast, PPy/chondroitin sulfate showed a
      significantly higher density of surface adhesion to the point where the
      distribution of adhesion effectively masked the topography. Through conductive
      AFM imaging, we found that the conductive regions correlated with regions of FN
      adhesion. CONCLUSIONS: Given that the conductivity requires doping of the
      polymer, these findings suggest that FN adhesion is mediated by interactions with
      chondroitin sulfate and hyaluronic acid at the polymer surface and may be
      indicative of specific interactions due to contributions from electrostatic
      attraction between the FN and sulfate/anionic groups of the dopants. GENERAL
      SIGNIFICANCE: This study demonstrates the ability of AFM to resolve the protein
      conducting polymer interactions at the molecular and nanoscale level, which will
      be important for interfacing these polymer materials with biological systems.
      This article is part of a Special Issue entitled Organic Bioelectronics - Novel
      Applications in Biomedicine.

PMID- 23531423
TI  - Correlation of circulating C1q and C1q-binding adiponectin concentrations with
      aging in males: a preliminary report.
AB  - BACKGROUND: Atherosclerosis is an age-related disease. Adiponectin and C1q form a
      protein complex in human blood, and that serum C1q and C1q-binding adiponectin
      (C1q-APN) concentrations can be measured. We investigated circulating C1q and C1q
      APN levels in Japanese men including elderly men. FINDINGS: The study subjects
      were 509 Japanese men including elderly men. Serum levels of total adiponectin
      (Total-APN), high-molecular weight-adiponectin (HMW-APN), C1q-APN and C1q were
      measured by enzyme-linked immunosorbent assay. Total-APN, HMW-APN and C1q-APN,
      but not C1q, correlated significantly and positively with aging (r=0.26, r=0.24,
      r=0.17, p<0.01, respectively). The HMW-APN/Total-APN ratio correlated
      significantly and positively with aging (r=0.14, p<0.01). The C1q-APN/Total-APN
      ratio and C1q-APN/HMW-APN ratio correlated significantly and negatively with
      aging (r=-0.17, p<0.01, r=-0.12, p=0.01). C1q-APN/C1q correlated significantly
      and positively with aging (r=0.09, p=0.03). Multiple regression analysis
      identified age and body mass index as significant determinants of C1q-APN.
      CONCLUSIONS: The present study demonstrates that serum HMW-APN, C1q-APN, and
      Total-APN, but not C1q, correlated positively with aging. These preliminary
      results could form the basis for future research. TRIAL REGISTRATION:  CLINICAL
      TRIAL REGISTRATION NUMBER: UMIN000004318.

PMID- 23531424
TI  - A low-residue diet improved patient satisfaction with split-dose oral sulfate
      solution without impairing colonic preparation.
AB  - BACKGROUND: Preprocedural dietary restrictions have been identified as a common
      reason potential candidates for colorectal cancer screening do not undergo
      colonoscopy as recommended. OBJECTIVE: To study whether a low-residue diet
      impacts bowel preparation with oral sulfate solution. DESIGN: Endoscopist
      blinded, prospective, randomized controlled trial. SETTING: Community-based
      outpatient ambulatory surgical center. PATIENTS: Patients scheduled for
      outpatient colonoscopy. INTERVENTIONS: Subjects were randomized to ingest either
      a low-residue diet of specified foods for breakfast, lunch, and snack or a clear
      liquid diet the day before the colonoscopy. MAIN OUTCOME MEASUREMENTS: The
      quality of the bowel preparation was assessed using the Boston Bowel Preparation
      Scale. Subject satisfaction with bowel preparation, diet, and severity of side
      effects was measured by a visual analog scale. RESULTS: Two hundred thirty
      subjects were recruited (114 clear liquid and 116 low residue). Mean preparation
      scores were not statistically different in either their segmental scores or total
      score. Subjects in the low-residue arm reported significantly higher satisfaction
      with bowel preparation medication, diet, and entire preparation process. Observed
      rates of side effects were low, and there was no statistical difference between
      the two groups. The rate of procedural cancellation was significantly higher in
      the clear liquid group compared with the low-residue group (20% vs 9%, P = .03).
      LIMITATIONS: Single-center study. CONCLUSIONS: A low-residue diet did not impair
      the quality of bowel preparation achieved with split-dose oral sulfate solution
      but did improve patient satisfaction.

PMID- 23531425
TI  - Second-look endoscopy is not associated with better clinical outcomes after
      gastric endoscopic submucosal dissection: a prospective, randomized, clinical
      trial analyzed on an as-treated basis.
AB  - BACKGROUND: The efficacy of routine second-look endoscopy (SLE) to detect or
      prevent bleeding after gastric endoscopic submucosal dissection (ESD) has not yet
      been validated. OBJECTIVE: The aim of this study was to determine whether SLE
      affects clinical outcomes including bleeding and morbidity after gastric ESD.
      DESIGN: A prospective, randomized, controlled study with consecutive data
      analyzed on an as-treated basis. SETTING: A single, tertiary-care referral
      center. PATIENTS: A total of 182 patients. INTERVENTION: Gastric ESD and SLE.
      MAIN OUTCOME MEASUREMENTS: Incidence of and risk factors related to bleeding
      after ESD and outcomes by univariate or multivariate analysis. RESULTS: Among 182
      patients enrolled, 74 and 81 patients were assigned to the SLE and no-SLE groups,
      respectively. Two groups were observed closely for 4 weeks. Bleeding occurred
      after ESD in 21 patients (13.5%). Hemoglobin loss (>=2.0 g/dL) was observed in 20
      patients, and melena developed in 1 patient after ESD. However, only 1 patient
      needed a transfusion. Twelve patients (16.2%) in the SLE group and 9 in the no
      SLE group (11.1%) experienced bleeding after ESD. The frequency of bleeding after
      ESD was not significantly different between the 2 groups (P = .66). There were no
      risk factors related to bleeding after ESD. LIMITATIONS: Single-center analysis.
      CONCLUSION: SLE is not routinely necessary because it does not affect clinical
      outcomes, including bleeding and morbidity after ESD. ( CLINICAL TRIAL
      REGISTRATION NUMBER: KCT0000146.).

PMID- 23531426
TI  - Validation of the Harefield Cleansing Scale: a tool for the evaluation of bowel
      cleansing quality in both research and clinical practice.
AB  - BACKGROUND: Variations in bowel cleansing quality before colonoscopy can cause
      confounding of results within clinical trials and inappropriate treatment
      decisions in clinical practice. A new tool-the Harefield Cleaning Scale-has been
      developed, which addresses the limitations of existing scales. OBJECTIVE:
      Validation exercise for the new cleansing scale. DESIGN: Retrospective validation
      study. SETTING: Various colonoscopy units in France. PATIENTS: Patients who had a
      total of 337 colonoscopies recorded. INTERVENTION: Video-recorded colonoscopy.
      MAIN OUTCOME MEASUREMENTS: Comparisons of 2 scoring systems to assess direct
      correlation, interrater reliability, internal consistency, and test-retest
      reliability, based on assessment of video recordings from 337 colonoscopies.
      RESULTS: Correlation analysis for expert scores by using the 2 scales yielded a
      Spearman correlation coefficient of 0.833. Similarly, the comparison of the
      segmental sum score revealed a Spearman correlation coefficient of -0.778. Cross
      tabulation for successful colon cleansing was 92.88% versus unsuccessful colon
      cleansing in 7.12%. Reliability assessment indicated an acceptable internal
      consistency with a Cronbach alpha coefficient of 0.81. Test-retest reliability
      demonstrated an overall agreement of 0.639 (kappa statistic). Receiver operating
      characteristic analysis versus Aronchick Scale scores yielded an area under the
      curve of 0.945, with sensitivity of 99% and specificity of 83% at the optimum
      score cut-off point. LIMITATIONS: Test-retest reliability was assessed by using a
      different patient population to the other measures. There were insufficient
      patient numbers to assess performance by using adenoma detection rate.
      CONCLUSION: This validation analysis has demonstrated that the Harefield
      Cleansing Scale is a robust, reliable, and consistent tool that has the potential
      to improve the effective standardization of bowel preparation assessment in both
      clinical and research practice.

PMID- 23531427
TI  - Surveillance and movements of Virginia opossum (Didelphis virginiana) in the
      bovine tuberculosis region of Michigan.
AB  - Wildlife reservoir hosts of bovine tuberculosis (bTB) include Eurasian badgers
      (Meles meles) and brushtail possum (Trichosurus vulpecula) in the UK and New
      Zealand, respectively. Similar species warrant further investigation in the
      northern lower peninsula of Michigan, USA due to the continued presence of bTB on
      cattle farms. Most research in Michigan, USA has focused on interactions between
      white-tailed deer (Odocoileus virginianus) and cattle (Bos taurus) for the
      transmission of the infectious agent of bTB, Mycobacterium bovis, due to high
      deer densities and feeding practices. However, limited data are available on
      medium-sized mammals such as Virginia opossum (Didelphis virginiana; hereafter
      referred to as opossum) and their movements and home range in Michigan near
      cattle farms. We conducted surveillance of medium-sized mammals on previously
      depopulated cattle farms for presence of M. bovis infections and equipped opossum
      with Global Positioning System (GPS) technology to assess potential differences
      in home range between farms inside and outside the bTB core area that has had
      cattle test positive for M. bovis. On farms inside the bTB core area, prevalence
      in opossum was comparable [6%, 95% confidence interval (CI) 2.0-11.0] to
      prevalence in raccoon (Procyon lotor; 4%, 95% CI 1.0-9.0, P=0.439) whereas only a
      single opossum tested positive for M. bovis on farms outside the bTB core area.
      The prevalence in opossum occupying farms that had cattle test positive for M.
      bovis was higher (6.4%) than for opossum occupying farms that never had cattle
      test positive for M. bovis (0.9%, P=0.01). Mean size of home range for 50% and
      95% estimates were similar by sex (P=0.791) both inside or outside the bTB core
      area (P=0.218). Although surveillance efforts and home range were not assessed on
      the same farms, opossum use of farms near structures was apparent as was
      selection for farms over surrounding forested habitats. The use of farms, stored
      feed, and structures by opossum, their ability to serve as vectors of M. bovis,
      and their propensity to ingest contaminated sources of M. bovis requires
      additional research in Michigan, USA.

PMID- 23531428
TI  - [Micrometastasis: biological entity and clinical impact?].
AB  - Micrometastases or sub-micrometastases can be detected by standard
      histopathological method sometimes associated with immunohistochemistry in lymph
      nodes, bone marrow and blood. The consequence of these small size involvement may
      be prognostic and therapeutic. Two factors are necessary to assess this kind of
      involvement: the rate of involvement of non-sentinel lymph node after axillary
      lymph node dissection and significative difference of survivals. The rate of
      involvement of non-sentinel lymph node in case of micrometastases or sub
      micrometastases is different from the rate of involvement in case of no lymph
      node metastases (7 to 8%) or in case of macrometases (30 to 50%). Micrometastase
      is an important factor to determine the rate of involvement of non-sentinel lymph
      node, the overall or disease free survival and to assess the need of radiotherapy
      and chemotherapy. In conclusion, micrometastases and sub-micrometastases have a
      clinical impact even if complementary axillary lymph node dissection is still
      discussed.

PMID- 23531429
TI  - Effects of serum testosterone levels after 6 months of androgen deprivation
      therapy on the outcome of patients with prostate cancer.
AB  - BACKGROUND: Controversy exists about whether testosterone serum levels at a
      cutoff point of < 50 ng/dL during luteinizing hormone-releasing hormone analogue
      (LHRHA) treatment are related to the outcome of patients with prostate cancer. We
      assessed the relationship between serum testosterone levels after 6 months of
      LHRHA therapy and disease outcome in a consecutive series of patients with
      prostate cancer. PATIENTS AND METHODS: Serum testosterone levels were measured
      prospectively in a cohort of patients given LHRHA for 6 months. End points were
      time to progression (TTP) and overall survival (OS). RESULTS: The study
      population was 153 patients: 54 with metastatic disease and 99 with biochemical
      failure. In multivariate analysis, adjustment for age, baseline serum prostatic
      specific antigen (PSA) levels, Gleason score, and disease stage, testosterone
      levels < 50 ng/dL failed to be associated with TTP and OS. A cutoff of < 20 ng/dL
      was associated with a nonsignificant lower risk of progression (adjusted hazard
      ratio [HR] 0.58; 95% confidence interval [CI] 0.30-1.15; P = .12) and a
      significant lower risk of death (adjusted HR, 0.19; 95% CI, 0.04-0.76; P = .02).
      Only 25 patients attained serum testosterone levels < 20 ng/dL. Using a receiver
      operating characteristic curve (ROC), we found that a testosterone value of 30
      ng/dL offered the best overall sensitivity and specificity for prediction of
      death. Serum testosterone levels < 30 ng/mL were associated with a significantly
      lower risk of death (adjusted HR, 0.45; 95% CI, 0.22-0.94; P = .034. CONCLUSIONS:
      Serum testosterone levels lower than the currently adopted cutoff of 50 ng/dL
      have a prognostic role in patients with prostate cancer receiving LHRHA and are a
      promising surrogate parameter of LHRHA efficacy.

PMID- 23531430
TI  - Promoting Darfuri women's psychosocial health: developing a war trauma counsellor
      training programme tailored to the person.
AB  - Women are considered special groups who are uniquely vulnerable in the context of
      war exposures. To effectively target the resources aimed at mitigating mental
      health consequences and optimising and maximising the use of mental health
      provisions, culturally relevant war trauma counsellor training is required. The
      objectives of this study are to promote a new philosophy in the Sudanese mental
      health care by introducing an integrative approach for targeted prevention and
      tailored treatments to the Darfuri person in a cost-effective way. Furthermore,
      the study provides evidence- and theory-based guidelines for developing a war
      trauma counsellor training programme in Sudan, mainly based on qualitative and
      quantitative studies among war-affected Darfuri female students. Cultural
      conceptualisations such as gender roles and religious expectations as well as
      theories that emphasise resilience and other psychosocial adaptation skills have
      been operationalised to reflect the totality of the Darfuri women's experiences.
      Furthermore, the results of four interrelated studies among war-traumatised
      undergraduate Darfuri women who are internally displaced provide the basis that
      guides an outline for qualification development, capacity building and skills
      consolidation among Sudanese mental health care providers. Explicit war-related
      psychosocial needs assessment tools, specific war-related trauma counsellor
      training and particular counsellor characteristics, qualities and awareness that
      pertain to strengthening the efficacy of war trauma Sudanese counsellors are
      recommended. The aim is to produce expertly trained war trauma counsellors
      working with war-affected Darfuri women in particular and with regards to their
      helpfulness in responding to the psychosocial needs of war-exposed Sudanese in
      general.

PMID- 23531431
TI  - Laboratory SIP signatures associated with oxidation of disseminated metal
      sulfides.
AB  - Oxidation of metal sulfide minerals is responsible for the generation of acidic
      waters rich in sulfate and metals. When associated with the oxidation of sulfide
      ore mine waste deposits the resulting pore water is called acid mine drainage
      (AMD); AMD is a known environmental problem that affects surface and ground
      waters. Characterization of oxidation processes in-situ is challenging,
      particularly at the field scale. Geophysical techniques, spectral induced
      polarization (SIP) in particular, may provide a means of such investigation. We
      performed laboratory experiments to assess the sensitivity of the SIP method to
      the oxidation mechanisms of common sulfide minerals found in mine waste deposits,
      i.e., pyrite and pyrrhotite, when the primary oxidant agent is dissolved oxygen.
      We found that SIP parameters, e.g., phase shift, the imaginary component of
      electrical conductivity and total chargeability, decrease as the time of exposure
      to oxidation and oxidation degree increase. This observation suggests that
      dissolution-depletion of the mineral surface reduces the capacitive properties
      and polarizability of the sulfide minerals. However, small increases in the phase
      shift and imaginary conductivity do occur during oxidation. These transient
      increases appear to correlate with increases of soluble oxidizing products, e.g.,
      Fe(2+) and Fe(3+) in solution; precipitation of secondary minerals and the
      formation of a passivating layer to oxidation coating the mineral surface may
      also contribute to these increases. In contrast, the real component of electrical
      conductivity associated with electrolytic, electronic and interfacial conductance
      is sensitive to changes in the pore fluid chemistry as a result of the soluble
      oxidation products released (Fe(2+) and Fe(3+)), particularly for the case of
      pyrrhotite minerals.

PMID- 23531432
TI  - Chronic intranasal deferoxamine ameliorates motor defects and pathology in the
      alpha-synuclein rAAV Parkinson's model.
AB  - Parkinson's disease is characterized by neuronal death in the substantia nigra
      and the presence of intracellular inclusions of alpha-synuclein in the Lewy
      bodies. Several lines of data support a role for iron in Parkinson's disease:
      iron is present in Lewy bodies, iron accumulates in the dopaminergic neurons in
      the substantia nigra, and Parkinson's disease is correlated with polymorphisms of
      several genes implicated in iron metabolism. Furthermore, iron can compromise the
      solubility of alpha-synuclein through direct interaction and can induce
      neurotoxicity in vitro. Here, we investigate the possible neuroprotective effect
      of the iron chelator deferoxamine in vivo to elucidate whether iron chelation can
      provide meaningful therapy for Parkinson's disease. Hence, we used a Parkinson's
      disease animal model based on unilateral injection of a recombinant adeno
      associated viral vector encoding alpha-synuclein in the rat midbrain. Rats were
      treated with a novel deferoxamine delivery approach: 6 mg of the compound was
      administered intranasally three times a week for 3 or 7 weeks. The behavior of
      the animals and histopathological changes in the brain were analyzed. Our data
      show that although intranasal administration of deferoxamine in rats did not
      protect them from dopaminergic cell death, it did decrease the number of the
      pathological alpha-synuclein formations at the terminal level. In addition, this
      treatment resulted in changes in the immune response and an overall partial
      improvement in motor behavior. Taken together, our data show that in vivo iron
      chelation can modulate alpha-synuclein-induced pathology in the central nervous
      system. Our data suggest that chronic administration of intranasal deferoxamine
      may be a valid approach to limiting the mishandling of alpha-synuclein in the
      central nervous system observed in Parkinson's disease and slowing disease
      progression.

PMID- 23531433
TI  - Impact of the Christchurch earthquakes on hospital staff.
AB  - INTRODUCTION: On September 4, 2010 a major earthquake caused widespread damage,
      but no loss of life, to Christchurch city and surrounding areas. There were
      numerous aftershocks, including on February 22, 2011 which, in contrast, caused
      substantial loss of life and major damage to the city. The research aim was to
      assess how these two earthquakes affected the staff in the General Medicine
      Department at Christchurch Hospital. Problem To date there have been no published
      data assessing the impact of this type of natural disaster on hospital staff in
      Australasia. METHODS: A questionnaire that examined seven domains (demographics,
      personal impact, psychological impact, emotional impact, impact on care for
      patients, work impact, and coping strategies) was handed out to General Medicine
      staff and students nine days after the September 2010 earthquake and 14 days
      after the February 2011 earthquake. RESULTS: Response rates were >= 99%. Sixty
      percent of responders were <30 years of age, and approximately 60% were female.
      Families of eight percent and 35% had to move to another place due to the
      September and February earthquakes, respectively. A fifth to a third of people
      had to find an alternative route of transport to get to work but only eight
      percent to 18% took time off work. Financial impact was more severe following the
      February earthquake, with 46% reporting damage of >NZ $1,000, compared with 15%
      following the September earthquake (P < .001). Significantly more people felt
      upset about the situation following the February earthquake than the September
      earthquake (42% vs 69%, P < .001). Almost a quarter thought that quality of
      patient care was affected in some way following the September earthquake but this
      rose to 53% after the February earthquake (12/53 vs 45/85, P < .001). Half
      believed that discharges were delayed following the September earthquake but this
      dropped significantly to 15% following the February earthquake (27/53 vs 13/62, P
      < .001). CONCLUSION: This survey provides a measure of the result of two major
      but contrasting Christchurch earthquakes upon General Medicine hospital staff.
      The effect was widespread with minor financial impact during the first but much
      more during the second earthquake. Moderate psychological impact was experienced
      in both earthquakes. This data may be useful to help prepare plans for future
      natural disasters. .

PMID- 23531434
TI  - Paternal stress prior to conception alters DNA methylation and behaviour of
      developing rat offspring.
AB  - Although there has been an abundance of research focused on offspring outcomes
      associated with maternal experiences, there has been limited examination of the
      relationship between paternal experiences and offspring brain development. As
      spermatogenesis is a continuous process, experiences that have the ability to
      alter epigenetic regulation in fathers may actually change developmental
      trajectories of offspring. The purpose of this study was to examine the effects
      of paternal stress prior to conception on behaviour and the epigenome of both
      male and female developing rat offspring. Male Long-Evans rats were stressed for
      27 consecutive days and then mated with control female rats. Early behaviour was
      tested in offspring using the negative geotaxis task and the open field. At P21
      offspring were sacrificed and global DNA methylation levels in the hippocampus
      and frontal cortex were analysed. Paternal stress prior to conception altered
      behaviour of all offspring on the negative geotaxis task, delaying acquisition of
      the task. In addition, male offspring demonstrated a reduction in stress
      reactivity in the open field paradigm spending more time than expected in the
      centre of the open field. Paternal stress also altered DNA methylation patterns
      in offspring at P21, global methylation was reduced in the frontal cortex of
      female offspring, but increased in the hippocampus of both male and female
      offspring. The results from this study clearly demonstrate that paternal stress
      during spermatogenesis can influence offspring behaviour and DNA methylation
      patterns, and these affects occur in a sex-dependent manner. Development takes
      place in the centre of a complex interaction between maternal, paternal, and
      environmental influences, which combine to produce the various phenotypes and
      individual differences that we perceive.

PMID- 23531436
TI  - Spiraling dopaminergic circuitry from the ventral striatum to dorsal striatum is
      an effective feed-forward loop.
AB  - Central dopamine systems are key players in the cerebral organization of behavior
      and in various neurological and psychiatric diseases. We demonstrate the presence
      of a neurochemical feed-forward loop characterized by region-specific changes in
      dopamine efflux in serially connected striatal regions, providing evidence in
      favor of the existence of so-called spiraling striato-nigro-striatal connections.
      Using in vivo microdialysis of rats, we show that simultaneous stimulation of
      dopamine D1 and D2 receptors in the accumbal shell decreased dorsal striatal
      dopamine efflux via a direct or indirect feed-forward loop involving shell, core,
      ventrolateral and dorsal part of the striatum: simultaneous stimulation of
      dopamine D1 and D2 receptors in the shell decreased dopamine efflux in the core;
      flupenthixol-induced inhibition of dopamine D1 and D2 receptors in the core
      increased dopamine efflux in the ventrolateral part of the striatum, and
      simultaneous stimulation of dopamine D1 and D2 receptors in the ventrolateral
      part of the striatum decreased dopamine efflux in the dorsal part of the
      striatum. Finally, simultaneous stimulation of dopamine D1 and D2 receptors in
      the shell decreased dopamine efflux in the dorsal part of the striatum. Thus,
      distinct striatal regions act also in series, providing a better understanding of
      the neural mechanisms underlying dopamine-dependent behaviors and the progression
      of dopamine-dependent disorders such as depression, schizophrenia, attention
      deficit hyperactivity disorder (ADHD), and addiction.

PMID- 23531435
TI  - Threat bias in mice with inactivating mutations of Prkar1a.
AB  - Anxiety disorders are associated with abnormalities in the neural processing of
      threat-related stimuli. However, the neurobiological mechanisms underlying threat
      bias in anxiety are not well understood. We recently reported that a Prkar1a
      heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the main regulatory
      subunit (R1alpha) of protein kinase A (PKA) exhibits an anxiety-like phenotype
      associated with increased cAMP signaling in the amygdala. Prkar1a(+/-) mice
      provide a novel model to test the direct effect of altered PKA expression and
      subsequent anxiety-like behavioral phenotype on the response to threat. We
      hypothesized that Prkar1a(+/-)mice would exhibit a bias in threat detection since
      increased amygdala activity during emotional stimuli is associated with a
      maladaptive response. We measured behavior and PKA activity in brain areas after
      exposure to predator or control odor exposure in male Prkar1a(+/-) and wild-type
      (WT) littermates. Indeed, there were significant differences in the behavioral
      response to threat detection; WT mice showed the expected response of decrease in
      exploratory behavior during predator vs. control odor exposure, while Prkar1a(+/
      ) mice did not alter their behavior between conditions. Basal and total PKA
      activity was independently associated with genotype, with an interaction between
      genotype and threat condition. Prkar1a(+/-) mice had higher PKA activity in
      amygdala and ventromedial hypothalamus in response to predator odor. In contrast,
      WT mice had higher PKA activity in amygdala and orbitofrontal cortex after
      exposure to control odor. Dysregulated PKA activity in the amygdala-prefrontal
      cortex circuitry in Prkar1a(+/-) mice is associated with behavioral phenotype of
      anxiety and a bias for threat. This is likely related to a failure to inhibit the
      amydgala response, which is an effect of the genotype. These results suggest that
      the alteration in PKA signaling in Prkar1a(+/-) mice is not ubiquitous in the
      brain; tissue-specific effects of the cAMP/PKA pathway are related to threat
      detection and fear sensitization.

PMID- 23531437
TI  - Sciatic nerve regeneration is not inhibited by anti-NGF antibody treatment in the
      adult rat.
AB  - Elevated nerve growth factor (NGF) is believed to play a role in many types of
      pain. An NGF-blocking antibody (muMab 911) has been shown to reduce pain and
      hyperalgesia in pain models, suggesting a novel therapeutic approach for pain
      management. Since NGF also plays important roles in peripheral nervous system
      development and sensory nerve outgrowth, we asked whether anti-NGF antibodies
      would adversely impact peripheral nerve regeneration. Adult rats underwent a
      unilateral sciatic nerve crush to transect axons and were subcutaneously dosed
      weekly for 8weeks with muMab 911 or vehicle beginning 1day prior to injury.
      Plasma levels of muMab 911 were assessed from blood samples and foot print
      analysis was used to assess functional recovery. At 8-weeks post-nerve injury,
      sciatic nerves were prepared for light and electron microscopy. In a separate
      group, Fluro-Gold was injected subcutaneously at the ankle prior to perfusion,
      and counts and sizes of retrogradely labeled and unlabeled dorsal root ganglion
      neurons were obtained. There was no difference in the time course of gait
      recovery in antibody-treated and vehicle-treated animals. The number of
      myelinated and nonmyelinated axons was the same in the muMab 911-treated crushed
      nerves and intact nerves, consistent with observed complete recovery. Treatment
      with muMab 911 did however result in a small decrease in average cell body size
      on both the intact and injured sides. These results indicate that muMab 911 did
      not impair functional recovery or nerve regeneration after nerve injury in adult
      rats.

PMID- 23531438
TI  - Comparison of brachial artery vascular responses among postmenopausal women
      receiving different doses of tibolone.
AB  - OBJECTIVE: To compare the effects of low and conventional doses of tibolone in
      brachial artery flux parameters among postmenopausal women. METHODS: Between
      March 2011 and September 2012, 24 postmenopausal women attending Gynecology and
      Obstetrics Hospital Luis Castelazo Ayala, Mexico City, for hormone replacement
      therapy were consecutively recruited. The women were alternately assigned to
      receive a daily dose of either 2.5mg (n=11) or 1.25mg (n=13) of oral tibolone.
      Before and after treatment, all women underwent a brachial artery Doppler
      ultrasound. The arterial diameter was measured, and the pulsatility index (PI)
      and the resistance index (RI) were calculated. A hyperemic stimulus was then
      induced and these parameters were measured again. RESULTS: Among the 24 women,
      the time since menopause ranged from 16 to 24 months, and the median treatment
      duration was 3 months. Both groups showed a significant increase in arterial
      diameter after treatment. There was no significant difference between the groups
      in arterial diameter, PI, and RI. The arterial diameter after hyperemic stimulus
      was significantly lower after treatment than before treatment in both groups.
      CONCLUSION: Low and conventional doses of tibolone induced similar changes in
      brachial artery flux parameters among postmenopausal women.

PMID- 23531439
TI  - Oropharyngeal dysphagia in an elderly post-operative hip fracture population: a
      prospective cohort study.
AB  - BACKGROUND: normal ageing processes impact on oropharyngeal swallowing function
      placing older adults at risk of developing oropharyngeal dysphagia (OD).
      Anecdotal clinical experience has observed that older patients recovering from
      hip fracture surgery commonly develop OD post-operatively. OBJECTIVE: to document
      the presence of OD following hip fracture surgery, and the factors associated
      with OD. METHODS: one hundred and eighty-one patients with a mean age of 83 years
      (range: 65-103) admitted to a specialised orthogeriatric unit were assessed for
      OD post-surgery for hip fracture. Pre-admission, intra-operative and post
      operative factors were examined to determine their relationship with the presence
      of OD. RESULTS: OD was found to be present post-operatively in 34% (n = 61) of
      the current population. Multivariate logistic regression analyses revealed the
      presence of pre-existing neurological and respiratory medical co-morbidities,
      presence of post-operative delirium, age and living in a residential aged care
      facility prior to hospital admission to be associated with the post-operative OD.
      CONCLUSION: these results highlight that OD is present in a large number of the
      older hip fracture population. Early identification of OD has important
      implications for the provision of timely dysphagia management that may prevent
      secondary complications and potentially reduce the hospital length of stay.

PMID- 23531440
TI  - Changes in hospitalisation and surgical procedures among the oldest-old: a follow
      up study of the entire Danish 1895 and 1905 cohorts from ages 85 to 99 years.
AB  - OBJECTIVE: to examine whether the Danish 1905 cohort members had more active
      hospital treatment than the 1895 cohort members from ages 85 to 99 years and
      whether it results in higher in-hospital and post-operative mortality. METHODS:
      in the present register-based follow-up study the complete Danish birth cohorts
      born in 1895 (n = 12,326) and 1905 (n = 15,477) alive and residing in Denmark at
      the age of 85 were followed from ages 85 to 99 years with regard to
      hospitalisations and all-cause and cause-specific surgical procedures, as well as
      in-hospital and post-operative mortality. RESULTS: the 1905 cohort members had
      more frequent hospital admissions and operations, but they had a shorter length
      of hospital stay than the 1895 cohort at all ages from 85 to 99 years. The
      increase in primary prosthetic replacements of hip joint was observed even within
      the 1895 cohort: no patients were operated at ages 85-89 years versus 2.2-3.6% at
      ages 95-99 years. Despite increased hospitalisation and operation rates, there
      was no increase in post-operative and in-hospital mortality rates in the 1905
      cohort. These patterns were similar among men and women. CONCLUSIONS: the
      observed patterns are compatible with more active treatment of the recent cohorts
      of old-aged persons and reduced age inequalities in the Danish healthcare system.
      No increase in post-operative mortality suggests that the selection of older
      patients eligible for a surgical treatment is likely to be based on the health
      status of old-aged persons and the safety of surgical procedures rather than
      chronological age.

PMID- 23531441
TI  - Head atonic attacks: a new type of benign non-epileptic attack in infancy
      strongly mimicking epilepsy.
AB  - Non-epileptic attacks (NEAs) are a heterogeneous group of clinical entities which
      often complicate the differential diagnosis of epilepsy. NEAs usually have a
      benign course and are limited to a specific period of life. If motor
      manifestations are strongly suggestive of an epileptic phenomenon, the risk of
      misdiagnosis is greater. Here, we describe a novel NEA with infantile onset,
      characterised by repeated head drops, mimicking epileptic negative myoclonus of
      the neck. The frequency of the episodes was very high, at hundreds or thousands
      per day. The episodes appeared in the second semester of the first year of life
      and spontaneously disappeared within a few months. [Published with video
      sequences].

PMID- 23531442
TI  - Design and evaluation of Lumefantrine - Oleic acid self nanoemulsifying ionic
      complex for enhanced dissolution.
AB  - BACKGROUND: Lumefantrine, an antimalarial molecule has very low and variable
      bioavailability owing to its extremely poor solubility in water. It is
      recommended to be taken with milk to enhance its solubility and bioavailability.
      The aim of present study was to develop a Self Nanoemulsifying Delivery system
      (SNEDs) of lumefantrine (LF) to achieve rapid and complete dissolution
      independent of food-fat and surfactant in dissolution media. METHODS: Solubility
      of LF in oil, co-solvent/co-surfactant and surfactant solution and emulsification
      efficiency of surfactant were analyzed to optimize the LF loaded self
      nanoemulsifying preconcentrate. Effect of LF-oleic acid complexation on
      emulsification, droplet size, zeta potential and dissolution were investigated.
      Effect of milk concentration and fat content on saturation solubility and
      dissolution of LF was investigated. Dissolution of marketed formulation and LF
      SNEDs was carried out in pH 1.2 and pH 6.8 phosphate buffer. RESULTS: LF
      exhibited very high solubility in oleic acid owing to complexation between
      tertiary amine of LF and carboxyl group of oleic acid (OA). Cremophore EL and
      medium chain monoglyceride were selected surfactant and co-surfactant,
      respectively. Significantly smaller droplet size (37 nm), shift in zeta potential
      from negative to positive value, very high drug loading in lipid based system (>
      10%), no precipitation after dissolution are the major distinguish
      characteristics contributed by LF-OA complex in the SNED system. Saturation
      solubility and dissolution study in milk containing media pointed the significant
      increment in solubility of LF in the presence of milk-food fat. LF-SNEDs showed >
      90% LF release within 30 min in pH 1.2 while marketed tablet showed almost 0%
      drug release. CONCLUSION: Self nanoemulsification promoting ionic complexation
      between basic drug and oleic acid hold great promise in enhancing solubility of
      hydrophobic drugs.

PMID- 23531443
TI  - Impaired Na+-dependent regulation of acetylcholine-activated inward-rectifier K+
      current modulates action potential rate dependence in patients with chronic
      atrial fibrillation.
AB  - Shortened action-potential duration (APD) and blunted APD rate adaptation are
      hallmarks of chronic atrial fibrillation (cAF). Basal and muscarinic (M)-receptor
      activated inward-rectifier K(+) currents (IK1 and IK,ACh, respectively)
      contribute to regulation of human atrial APD and are subject to cAF-dependent
      remodeling. Intracellular Na(+) ([Na(+)]i) enhances IK,ACh in experimental models
      but the effect of [Na(+)]i-dependent regulation of inward-rectifier K(+) currents
      on APD in human atrial myocytes is currently unknown. Here, we report a [Na(+)]i
      dependent inhibition of outward IK1 in atrial myocytes from sinus rhythm (SR) or
      cAF patients. In contrast, IK,ACh activated by carbachol, a non-selective M
      receptor agonist, increased with elevation of [Na(+)]i in SR. This [Na(+)]i
      dependent IK,ACh regulation was absent in cAF. Including [Na(+)]i dependence of
      IK1 and IK,ACh in a recent computational model of the human atrial myocyte
      revealed that [Na(+)]i accumulation at fast rates inhibits IK1 and blunts
      physiological APD rate dependence in both groups. [Na(+)]i-dependent IK,ACh
      augmentation at fast rates increased APD rate dependence in SR, but not in cAF.
      These results identify impaired Na(+)-sensitivity of IK,ACh as one potential
      mechanism contributing to the blunted APD rate dependence in patients with cAF.
      This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac
      Myocytes". 

PMID- 23531444
TI  - Insufficient versican cleavage and Smad2 phosphorylation results in bicuspid
      aortic and pulmonary valves.
AB  - Bicuspid or bifoliate aortic valve (BAV) results in two rather than three cusps
      and occurs in 1-2% of the population placing them at higher risk of developing
      progressive aortic valve disease. Only NOTCH-1 has been linked to human BAV, and
      genetically modified mouse models of BAV are limited by low penetrance and
      additional malformations. Here we report that in the Adamts5(-/-) valves,
      collagen I, collagen III, and elastin were disrupted in the malformed hinge
      region that anchors the mature semilunar cusps and where the ADAMTS5 proteoglycan
      substrate versican, accumulates. ADAMTS5 deficient prevalvular mesenchyme also
      exhibited a reduction of alpha-smooth muscle actin and filamin A suggesting
      versican cleavage may be involved in TGFbeta signaling. Subsequent evaluation
      showed a significant decrease of pSmad2 in regions of prevalvular mesenchyme in
      Adamts5(-/-) valves. To test the hypothesis that ADAMTS5 versican cleavage is
      required, in part, to elicit Smad2 phosphorylation we further reduced Smad2 in
      Adamts5(-/-) mice through intergenetic cross. The Adamts5(-/-);Smad2(+/-) mice
      had highly penetrant BAV and bicuspid pulmonary valve (BPV) malformations as well
      as increased cusp and hinge size compared to the Adamts5(-/-) and control
      littermates. These studies demonstrate that semilunar cusp malformations (BAV and
      BPV) can arise from a failure to remodel the proteoglycan-rich provisional ECM.
      Specifically, faulty versican clearance due to ADAMTS5 deficiency blocks the
      initiation of pSmad2 signaling, which is required for excavation of endocardial
      cushions during aortic and pulmonary valve development. Further studies using the
      Adamts5(-/-); Smad2(+/-) mice with highly penetrant and isolated BAV, may lead to
      new pharmacological treatments for valve disease.

PMID- 23531445
TI  - Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in
      vitro and in vivo.
AB  - The enzyme COX-2 is induced at high levels in tumors but not in surrounding
      normal tissues, which makes it an attractive target for molecular imaging of
      cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to
      detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show
      that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells
      in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show
      specific uptake of fluorocoxib A by COX-2-expressing K9TCC xenograft tumors in
      vivo. Fluorocoxib A uptake by COX-2-expressing xenograft tumors was blocked by
      70% (P < 0.005) when pretreated with the COX-2 selective inhibitor, celecoxib (10
      mg/kg), 4 hours before intravenous administration of fluorocoxib A (1 mg/kg).
      Fluorocoxib A was taken up by COX-2-expressing tumors but not by COX-2-negative
      human UMUC-3 xenograft tumors. UMUC-3 xenograft tumors with no expression of COX
      2 showed no uptake of fluorocoxib A. In addition, fluorocoxib A uptake was
      evaluated in five dogs diagnosed with TCC. Fluorocoxib A specifically detected
      COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal
      urothelium. Taken together, our findings show that fluorocoxib A selectively
      bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC
      xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in
      vivo. Spontaneous cancers in companion animals offer a unique translational model
      for evaluation of novel imaging and therapeutic agents using primary cancer cells
      in vitro and in heterogeneous cancers in vivo.

PMID- 23531446
TI  - Increased levels of urinary PGE-M, a biomarker of inflammation, occur in
      association with obesity, aging, and lung metastases in patients with breast
      cancer.
AB  - Elevated levels of COX-derived prostaglandin E2 (PGE2) occur in inflamed tissues.
      To evaluate the potential links between inflammation and breast cancer, levels of
      urinary prostaglandin E metabolite (PGE-M), a stable end metabolite of PGE2, were
      quantified. We enrolled 400 patients with breast cancer: controls with early
      breast cancer (n = 200), lung metastases (n = 100), and metastases to other sites
      (n = 100). Patients completed a questionnaire, provided urine, and had
      measurements of height and weight. Urinary PGE-M was quantified by mass
      spectrometry. Ever smokers with lung metastasis who had not been exposed to
      nonsteroidal anti-inflammatory drugs (NSAIDs) had the highest PGE-M levels. PGE-M
      levels were increased in association with elevated body mass index (BMI; P <
      0.001), aging (P < 0.001), pack-year smoking history (P = 0.02), lung metastases
      (P = 0.02), and recent cytotoxic chemotherapy (P = 0.03). Conversely, use of
      NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M
      levels (P < 0.001). On the basis of the current findings, PGE-M is likely to be a
      useful biomarker for the selection of high-risk subgroups to determine the use of
      interventions that aim to reduce inflammation and possibly the development and
      progression of breast cancer, especially in overweight and obese women.

PMID- 23531447
TI  - Effect of intermittent dosing regimens of erlotinib on methylnitrosourea-induced
      mammary carcinogenesis.
AB  - EGF receptor (EGFR) inhibitors are used in the therapy of lung and pancreatic
      cancers and effectively prevent cancers in multiple animal models. Although daily
      dosing with erlotinib is effective, weekly dosing may reduce toxicity and have
      advantages, particularly for prevention. We tested alternative dosing regimens
      for preventive/therapeutic efficacy in a rat mammary cancer model. For
      prevention, erlotinib was administered by gavage beginning 5 days after
      methylnitrosourea (MNU). For therapy and biomarker studies, rats with palpable
      mammary cancers were treated for six weeks or for six days, respectively.
      Experiment A, erlotinib (6 mg/kg body weight/day, intragastric): daily (7
      times/week); one day on/one day off; and two days on/two days off. All regimens
      decreased tumor incidence, increased tumor latency, and decreased cancer
      multiplicity versus controls (P < 0.01). However, intermittent dosing was less
      effective than daily dosing (P < 0.05). Experiment B, erlotinib (6 mg/kg body
      weight/day) daily or two days on/two days off or one time per week at 42 mg/kg
      body weight. All regimens reduced cancer incidence and multiplicity versus
      controls (P < 0.01). Interestingly, daily and weekly dosing were equally
      effective (P > 0.5). Experiment C, erlotinib administered at 42 or 21 mg/kg body
      weight 1 time per week, decreased tumor incidence and multiplicity (P < 0.01).
      Erlotinib had a serum half-life of <= 8 hours and weekly treatment yielded
      effective serum levels for <= 48 hours. Daily or weekly treatment of cancer
      bearing rats reduced mammary tumor size 25% to 35%, whereas control cancers
      increased >250%. Levels of phosphorylated extracellular signal-regulated kinase
      (ERK) were strongly decreased in rats treated daily/weekly with erlotinib. Thus,
      altering the dose of erlotinib retained most of its preventive and therapeutic
      efficacy, and based on prior clinical studies, is likely to reduce its toxicity.

PMID- 23531448
TI  - MicroRNA and cancer chemoprevention.
AB  - MicroRNAs (miRNA) are a group of naturally occurring, small, noncoding, and
      single-strand RNA molecules that regulate gene expression at the
      posttranscriptional and translational levels. By controlling the expression of
      oncogenic and tumor suppressor proteins, miRNAs are believed to play an important
      role in pathologic processes associated with malignant progression including
      tumor cell proliferation, apoptosis, differentiation, angiogenesis, invasion, and
      metastasis. However, relatively few studies have investigated the influence of
      chemopreventive agents on miRNA expression and their regulation of target genes.
      Given the significance of miRNAs in modulating gene expression, such research can
      provide insight into the pleiotropic biologic effects that chemopreventive agents
      often display and a deeper understanding of their mechanism of action to inhibit
      carcinogenesis. In addition, miRNAs can provide useful biomarkers for assessing
      antineoplastic activity of these agents in preclinical and clinical observations.
      In this review, we summarize recent publications that highlight a potentially
      important role of miRNAs in cancer chemoprevention research.

PMID- 23531449
TI  - Identification of lifestyle patterns associated with obesity and fat mass in
      children: the Healthy Growth Study.
AB  - OBJECTIVE: To investigate possible associations of lifestyle patterns with
      obesity and fat mass in children. DESIGN: Cross-sectional epidemiological study.
      Principal component analysis was used to identify lifestyle patterns. SETTING:
      Primary schools from four regions in Greece. SUBJECTS: A total of 2073
      schoolchildren (aged 9-13 years). RESULTS: Children in the fourth quartile of the
      lifestyle pattern combining higher dairy foods with more adequate breakfast
      consumption were 39.4%, 45.2% and 32.2% less likely to be overweight/obese and in
      the highest quartile of sum of skinfold thicknesses and fat mass, respectively,
      than children in the first quartile of this pattern. Similarly, children in the
      fourth quartile of a lifestyle pattern comprising consumption of high-fibre
      foods, such as fruits, vegetables and wholegrain products, were 27.4% less likely
      to be in the highest quartile of sum of skinfold thicknesses than children in the
      first lifestyle pattern quartile. Finally, children in the fourth quartile of a
      lifestyle pattern characterized by more time spent on moderate-to-vigorous
      physical activity and more frequent meals were 38.0%, 26.3% and 29.5% less likely
      to be overweight, centrally obese and in the highest quartile of fat mass,
      respectively, than their peers in the first quartile of this lifestyle pattern
      (all P < 0.05). CONCLUSIONS: The current study identified three lifestyle
      patterns (i.e. one pattern comprising higher dairy consumption with a more
      adequate breakfast; a second pattern characterized by increased consumption of
      high-fibre foods; and a third pattern combining higher physical activity levels
      with more frequent meals), which were all related with lower odds of obesity
      and/or increased fat mass levels. From a public health perspective, promotion of
      these patterns among children and their families should be considered as one of
      the components of any childhood obesity preventive initiative.

PMID- 23531450
TI  - Relationship between chemokine (C-X-C motif) ligand 12 gene variant (rs1746048)
      and coronary heart disease: case-control study and meta-analysis.
AB  - The goal of our study is to evaluate the contribution of CXCL12 rs1746048 (hg19,
      chr10:44775574) to the risk of CHD in Han Chinese, and to summarize its role in
      CHD through meta-analysis of existing studies among various ethnic groups.
      Significant association is observed between rs1746048-C and an increased risk of
      CHD in Han Chinese (chi(2)=5.41, df=1, P=0.02). Post hoc analysis reveals an even
      stronger association of rs1746048 with the risk of CHD for subjects aged 65 years
      or older (genotype: chi(2)=8.39, df=2, P=0.015; allele: chi2=9.13, df=1, P=0.003,
      odd ratio (OR)=1.91, 95% confidential interval (CI)=1.25-2.91). A break down
      analysis by gender shows that rs1746048 is likely a CHD risk factor under the
      recessive model in males (CC+CT versus TT: P=0.05, chi(2)=3.59, df=1, OR=1.72,
      95% CI=1.00-3.04). In addition, a meta-analysis of ten studies among over 107,000
      individuals confirms that rs1746048 is a risk factor of CHD (P<0.0001, OR=1.12,
      95% CI=1.09-1.15) and this agrees with the findings of our case-control study in
      Han Chinese.

PMID- 23531451
TI  - A novel mutation in the SLCO2A1 gene in a Chinese family with primary
      hypertrophic osteoarthropathy.
AB  - Primary hypertrophic osteoarthropathy (PHO) is a rare monogenetic disease that
      closely mimics hypertrophic osteoarthropathy secondary to pulmonary or other
      pathology. The study of PHO provides an opportunity to understand both the
      pathogenesis of hypertrophic osteoarthropathy and the functions of the underlying
      genes. PHO is characterized by digital clubbing, periostosis and pachydermia. Two
      genes are known to be related to PHO: SLCO2A1 and HPGD. Here, we identified a
      recurrent heterozygous guanine-to-adenine transition at the invariant +1 position
      of the donor site of intron 7 (c.940+1G>A) and a novel heterozygous missense
      mutation p.Asn534Lys (c.1602C>A) in exon 11 of SLCO2A1 in a Chinese young man
      with PHO. Identification of a novel genotype in PHO will provide clues to the
      phenotype-genotype relations and may assist not only in the clinical diagnosis of
      PHO but also in the interpretation of genetic information used for prenatal
      diagnosis and genetic counseling.

PMID- 23531452
TI  - Arsenic sorption by nanocrystalline magnetite: an example of environmentally
      promising interface with geosphere.
AB  - In this paper, the sorption of arsenic onto nanocrystalline magnetite mineral
      Fe3O4 was studied in a model system. Nanocrystalline magnetite was produced by
      mechanical activation in a planetary ball mill from natural microcrystalline
      magnetite. As a consequence of milling, the specific surface area increased from
      0.1m(2)/g to 11.9 m(2)/g and the surface site concentration enhanced from 2.2
      sites/nm(2) to 8.4 sites/nm(2). These changes in surface properties of magnetite
      lead to the enhancement of arsenic removal from model system. The best sorption
      ability was achieved with magnetite sample activated for 90 min. In this case the
      sample was able to absorb around 4 mg/g. The structural changes of magnetite were
      also observed and the new hematite phase was detected after 120 min of milling. A
      good correlation between the decreasing particle size, increasing specific
      surface area and reduction of saturation magnetization was found. In desorption
      study, KOH and NaOH were found as the best eluents where more than 70% of arsenic
      was released back into the solution. The principal novelty of the paper is that
      mineral magnetite, truly one nature's gift can be used after "smart" milling
      (mechanical activation) as an effective arsenic sorbent.

PMID- 23531455
TI  - Intracranial video-EEG and surgery for focal atonic seizures.
AB  - Atonic seizures are epileptic attacks characterised by a sudden loss or
      diminution of muscle tone. Structures corresponding to inhibitory cortical areas,
      such as the primary negative motor area or the supplementary negative motor area,
      could be responsible. We present findings observed in a patient with atonic
      seizures due to focal epilepsy, who underwent intracranial video-EEG monitoring
      and epilepsy surgery, and discuss possible underlying mechanisms. [Published with
      video sequences].

PMID- 23531453
TI  - Lack of functionally active sweet taste receptors in the jejunum in vivo in the
      rat.
AB  - BACKGROUND: When studied in enterocyte-like cell lines (Caco-2 and RIE cells),
      agonists and antagonists of the sweet taste receptor (STR) augment and decrease
      glucose uptake, respectively. We hypothesize that exposure to STR agonists and
      antagonists in vivo will augment glucose absorption in the rat. MATERIALS AND
      METHODS: About 30-cm segments of jejunum in anesthetized rats were perfused with
      iso-osmolar solutions containing 10, 35, and 100 mM glucose solutions (n = 6
      rats, each group) with and without the STR agonist 2 mM acesulfame potassium and
      the STR inhibitor 10 MUM U-73122 (inhibitor of the phospholipase C pathway).
      Carrier-mediated absorption of glucose was calculated by using stereospecific and
      nonstereospecific (14)C-d-glucose and (3)H-l-glucose, respectively. RESULTS:
      Addition of the STR agonist acesulfame potassium to the 10, 35, and 100 mM
      glucose solutions had no substantive effects on glucose absorption from 2.1 +/-
      0.2 to 2.0 +/- 0.3, 5.8 +/- 0.2 to 4.8 +/- 0.2, and 15.5 +/- 2.3 to 15.7 +/- 2.7
      MUmoL/min/30-cm intestinal segment (P > 0.05), respectively. Addition of the STR
      inhibitor (U-73122) also had no effect on absorption in the 10, 35, and 100 mM
      solutions from 2.3 +/- 0.1 to 2.1 +/- 0.2, 7.7 +/- 0.5 to 7.2 +/- 0.5, and 15.7
      +/- 0.9 to 15.2 +/- 1.1 MUmoL/min/30-cm intestinal segment, respectively.
      CONCLUSIONS: Provision of glucose directly into rat jejunum does not augment
      glucose absorption via STR-mediated mechanisms within the jejunum in the rat. Our
      experiments show either no major role of STRs in mediating postprandial
      augmentation of glucose absorption or that proximal gastrointestinal tract
      stimulation of STR or other luminal factors may be required for absorption of
      glucose to be augmented by STR.

PMID- 23531456
TI  - Clinical and radiological evaluation of sacroiliac joints compared with
      ultrasound examination in early spondyloarthritis.
AB  - OBJECTIVE: To compare clinical and X-ray examinations with US findings of SI
      joints (SIJ) in early SpA patients. METHODS: Twenty-three early SpA patients,
      diagnosed according to Assessment of SpondyloArthritis international Society
      criteria, were investigated clinically [sacral sulcus tenderness, BASMI, BASFI,
      BASDAI, pain and fatigue visual analogue scale (VAS), morning stiffness and sleep
      disturbance], with SIJ X-rays (New York score) and with My Lab70 US 7-10 MHz US
      (Esaote, Genoa, Italy), evaluating the width of the SIJ capsule and posterior
      sacroiliac (PSL) and sacrotuberosus (STL) ligament thickness and comparing the
      results with 23 healthy controls. RESULTS: SIJ width [right 2.2 (0.6) and left
      2.3 (0.7) in SpA vs 1.6 (0.1) and 1.7 (0.2) in healthy controls, respectively,
      expressed as mean (s.d.)] and STL thickness [right 3.9 (1.3) and left 3.4 (1.0)
      vs 1.8 (0.1) and 1.8 (0.1), respectively, expressed as mean (s.d.)] were higher
      in SpA patients than in controls (P < 0.001 and P < 0.05, respectively). PSL
      thickness was similar in patients and controls. Only STL thickness was higher
      when SIJ was tender at clinical examination (P < 0.01) and correlated with pain
      VAS (P < 0.001) and BASFI (P < 0.05). Furthermore, SIJ US results were unrelated
      to X-ray findings (similar when X-ray sacroiliitis was present and not).
      CONCLUSION: Our exploratory study suggested that in early SpA patients US might
      be a promising method, complementary to other imaging techniques, to study
      articular and soft tissue periarticular involvement of SIJ, independent of
      clinical and X-ray examination.

PMID- 23531454
TI  - Dobutamine-mediated heme oxygenase-1 induction via PI3K and p38 MAPK inhibits
      high mobility group box 1 protein release and attenuates rat myocardial
      ischemia/reperfusion injury in vivo.
AB  - BACKGROUND: It has been reported that the induction of heme oxygenase-1 (HO-1)
      mediated by beta1-adrenergic receptor inhibits high mobility group box 1 protein
      (HMGB1) release and increases the survival rate in cecal ligation and puncture
      induced septic mice. The present study aimed to investigate whether dobutamine, a
      selective beta1-adrenergic receptor agonist, could inhibit HMGB1 release via
      beta1-adrenergic receptor-mediated HO-1 induction and attenuate myocardial
      ischemia/reperfusion (I/R) injury in rats. MATERIALS AND METHODS: Anesthetized
      male rats were pretreated with dobutamine (5 or 10 MUg. Kg-1. min-1, intravenous)
      before ischemia in the absence and/or presence of LY294002 (0.3 mg/Kg), a
      phosphatidylinositol 3-kinase (PI3K)< inhibitor; SB203580 (1 mg/Kg), a p38
      mitogen-activated-protein kinase (P38 mitogen-activated-protein kinase [p38
      MAPK]) inhibitor, and zinc protoporphyrin IX ([ZnPPIX], 10 mg/Kg), a HO-1
      inhibitor, respectively, and then subjected to ischemia for 30 min followed by
      reperfusion for 4 h. The myocardial I/R injury and oxidative stress were
      assessed. Likewise, the expressions of HO-1 protein, nuclear factor kappa B (NF
      kappaB) p65, and HMGB1 were measured by Western blot analysis. RESULTS:
      Dobutamine significantly and dose-dependently attenuated myocardial I/R injury,
      reduced oxidative stress, and caused the induction of HO-1, the reduction of NF
      kappaB activation and HMGB1 over expression. However, all the effects caused by
      dobutamine were significantly reversed by the presence of LY294002, SB203580, and
      ZnPPIX, respectively. CONCLUSIONS: The present study demonstrated that dobutamine
      mediated the induction of HO-1 by selectively stimulating beta1-adrenergic
      receptor via PI3K and p38 MAPK, which inhibited HMGB1 release and attenuated rat
      myocardial I/R injury in vivo.

PMID- 23531457
TI  - Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in
      postmortem brain of subjects with autism.
AB  - BACKGROUND: Accumulating evidence suggests that dysfunction in the glutamatergic
      system may underlie the pathophysiology of autism. The anterior cingulate cortex
      (ACC) has been implicated in autism as well as in glutamatergic
      neurotransmission. We hypothesized that alterations in the glutamate-glutamine
      cycle in the ACC might play a role in the pathophysiology of autism. METHODS: We
      performed Western blot analyses for the protein expression levels of enzymes in
      the glutamate-glutamine cycle, including glutamine synthetase, kidney-type
      glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the
      ACC of postmortem brain of individuals with autism (n = 7) and control subjects
      (n = 13). RESULTS: We found that the protein levels of kidney-type glutaminase,
      but not those of the other enzymes measured, in the ACC were significantly lower
      in subjects with autism than in controls. CONCLUSION: The results suggest that
      reduced expression of kidney-type glutaminase may account for putative
      alterations in glutamatergic neurotransmission in the ACC in autism.

PMID- 23531458
TI  - Synthesis and biological evaluation of oleanolic acid derivatives as PTP1B
      inhibitors.
AB  - Twenty-four sugar-substituted oleanolic acid derivatives (1a-1f, 2a-2j, and 3a
      3h) were synthesized in a concise and efficient strategy and their effects on the
      inhibition of protein tyrosine phosphatase 1B (PTP1B) and insulin-sensitizing
      response were evaluated in vitro. Several derivatives showed moderate to good
      inhibitory activities against PTP1B, and especially compounds 2f, 2h, 3d and 3e
      exhibited the most potent inhibitory activities with the IC50 values of 1.91,
      12.2, 9.21 and 0.56 MUM against PTP1B, respectively. Furthermore, compounds 2g-2h
      and 3b-3e displayed good insulin-sensitizing activities with the response values
      ranging from 21.52% to 59.58%. Structure-activity relationship study of these
      sugar-substituted oleanolic acid derivatives demonstrated that PTP1B inhibitory
      activity and insulin-sensitizing response were strongly influenced by both the
      carbohydrate moiety at the C-3 position and the long acidic chain at C-28
      position of oleanolic acid.

PMID- 23531459
TI  - Intake of game birds in the UK: assessment of the contribution to the dietary
      intake of lead by women of childbearing age and children.
AB  - OBJECTIVE: Concern has recently been expressed about Pb levels in Pb-shot game
      meat. Our aim was to determine the consumption of game birds in a representative
      sample population in the UK, and in children and women of childbearing age in
      particular. DESIGN: Population-based cross-sectional cohort study. Data from 4 d
      diet diaries from the UK National Diet and Nutrition Survey (NDNS; 2008-2010)
      were extracted to analyse data on game bird consumption in the sample population,
      in women of childbearing age (15-45 years old) and in children <=6 years old.
      SETTING: Home-based study in representative areas of the UK. SUBJECTS:
      Participants in the NDNS (2008-2010; n 2126, age 1.5 to >65 years). RESULTS:
      Fifty-eight participants (2.7 %) reported eating game birds. The mean intake was
      19.5 (sd 18.1) g/d (median 15.6, range 1.3-92.9 g/d). In women of childbearing
      age (15-45 years), 11/383 (2.9 %) reported eating game birds, with a mean intake
      of 22.4 (sd 25.8) g/d (median 15.6, range 2.0-92.9 g/d). In children aged <=6
      years old, 3/342 (0.9 %) were reported as eating game birds, with a mean intake
      of 6.8 (sd 9.7) g/d (median 2.4, range 1.3-23.2 g/d). CONCLUSIONS: The prevalence
      of consumption of game birds by women of childbearing age and children <=6 years
      old was relatively low and intakes were small. However, any exposure to Pb in
      these two groups is undesirable. As are uncertainties about the ability of the
      diet diary method to capture the consumption of food items that are infrequently
      consumed, alternative methods of capturing these data should be used in future
      studies.

PMID- 23531460
TI  - Experiences of Alaskan parents with children hospitalized for respiratory
      syncytial virus treatment.
AB  - The purpose of this study was to describe the experiences of Alaskan parents with
      children hospitalized for the treatment of the respiratory syncytial virus (RSV).
      Six parents participated in a qualitative descriptive study composed of
      individual interviews. Using content analysis, three major themes emerged: "RSV
      is scary," "Lots of stress; little rest" and "At what point does it become a
      Bingo? He's going to the hospital." Findings provided further insight into the
      educational needs of the participants. Advanced practice registered nurses can
      translate insights provided by the participants into crucial knowledge needed for
      the care of families at heightened risk and currently experiencing RSV. 

PMID- 23531461
TI  - Fun and fit: evaluation of a pediatric exercise program.
AB  - While the components of effective pediatric exercise interventions have been
      identified in structured research settings, recent reviews have highlighted the
      need for translating these interventions into accessible programs. In this paper
      we evaluate a behavioral intervention-based exercise program designed to serve
      community children and teens at risk for adult obesity. Measures of weight,
      strength, cardiovascular fitness, and exercise intensity improved significantly
      over the course of this program, and qualitative assessments indicated that
      attitudes towards exercise also improved. Our experiences suggest that
      structured, protocol-driven exercise interventions can be successfully translated
      into effective programs accessible to children of different ages and
      socioeconomic levels. 

PMID- 23531462
TI  - A clinical tool for evaluating emotional well-being: self-drawings of
      hospitalized children.
AB  - This study investigated how the emotional wellbeing of children with congenital
      heart defect (CHD) hospitalized for heart surgery was expressed in self-drawings
      before and after their surgical treatment. A sample of 293 children produced self
      drawings (hospitalized n=168, non-hospitalized n=125). The results indicate
      significant differences between drawings by hospitalized compared to non
      hospitalized children, including size, color and omission of body parts. These
      differences were interpreted in line with previous analyses of projective
      drawing. We conclude that self-drawing evaluation is a useful tool to reveal
      insights into emotional wellbeing, promoting safe and easy communication. 

PMID- 23531464
TI  - Quiet time in a pediatric medical/surgical setting.

PMID- 23531463
TI  - Reducing pediatric overweight: nurse-delivered motivational interviewing in
      primary care.
AB  - The purpose of this study was to test the Let's Go 5-2-1-0 program delivered
      through motivational interviewing by nurses with 4-18-year-old overweight
      children and parents in primary care (PC). A quasi-experimental design allocated
      60 control families to standard clinical care (SCC) and 70 families to SCC plus
      the 5-2-1-0 intervention. Drop-out rates were 9 and 35% at 6 months and 25 and
      41% at 12 months, respectively for control and intervention participants. BMI
      percentile trended (p = .057) toward decline (M change = -3.0 versus -1.5) for
      intervention children at 6 months (n = 52 control, 44 intervention), and
      nonsignificantly (p = 0.14) for both groups (43 control, 40 intervention) at 12
      months (controls -1.9, intervention -4.6). Intervention effects were found for
      self-reported daily fruit/vegetable consumption, physical activity, and screen
      time. Satisfaction was high. Further study of the PC nursing intervention is
      warranted.

PMID- 23531465
TI  - Transferring central line care evidence into practice on pediatric acute care
      units.
AB  - The purpose of this study was to examine the effectiveness of an educational
      intervention to implement evidence based guidelines for central line care. Full
      time nurses working on pediatric inpatient units were surveyed before and after
      the multi-component educational intervention directed at implementation of the
      central line care bundle. There was a statistically significant increase in the
      nurses' self-reported compliance with components of the care bundle 6 months
      after the educational intervention (p<.001), thus improving central line care and
      infection prevention.

PMID- 23531466
TI  - The immobile pediatric population: can progressive mobility hasten recovery?

PMID- 23531467
TI  - Eating behaviors, diet quality, and gastrointestinal symptoms in children with
      autism spectrum disorders: a brief review.
AB  - Children with autism spectrum disorders (ASD) and their caregivers face unique
      challenges in the children's daily eating routines and food intake patterns. The
      aim of this brief review is to describe eating behaviors of children with ASD,
      including increased food neophobia and food selectivity, and review findings on
      children's diet quality, and gastrointestinal (GI) symptoms. Advancing knowledge
      about the interrelationships between these nutrition-related domains in children
      with ASD is expected to have important implications for clinical nursing practice
      and caregiver care. 

PMID- 23531468
TI  - Action competence obstacles to managing childhood overweight: in-depth interviews
      with mothers of 7- to 9-year-old children.
AB  - This qualitative phenomenological study interviewed seven mothers to overweight
      children and six mothers to non-overweight children aged 7 to 9 years old about
      their views and experiences with preventing and managing overweight in their
      children. The essence was that the mothers felt responsible for their children's
      habits, including those leading to overweight. They also felt that competent and
      had the opportunity to take preventive measures against child overweight but they
      did not always have the energy to do so. Even resourceful mothers required
      support from nurses and health professionals. Our results contribute to better
      understanding how to approach, motivate and support mothers to draw on their own
      competencies to benefit their children's weight and health.

PMID- 23531469
TI  - Strategies used by teens growing up in families with Huntington disease.
AB  - The purpose of this study was to identify helpfulness of strategies used by teens
      growing up in families with Huntington disease (HD). Forty-four participants
      responded to a mailed HD Family Survey-Teens Strategies. Strategies were those
      with strong positive correlation between use and perceived helpfulness, and those
      with negative or inverse relationships. Obtaining information, thinking about or
      doing something else, and actions on behalf of the parent with HD were rated as
      highest use and perceived helpfulness. Emotional suppression had high use but low
      helpfulness. Participants reported using numerous helpful strategies. Social
      support was often unavailable to help manage teen concerns. 

PMID- 23531470
TI  - Transition of health care from pediatric to adult care.

PMID- 23531471
TI  - Effects of dopamine agonists on calling behavior in the green tree frog, Hyla
      cinerea.
AB  - Dopamine (DA) is an important neurotransmitter involved in social behaviors, such
      as courtship and pair-bonding. In the green tree frog (Hyla cinerea), calling
      behavior is the primary social behavior used for mate attraction, and is critical
      for the reproductive success of the species. Our study examined how DA influences
      advertisement calling behavior of the green tree frog. In a field environment,
      calling males were treated with either a DA receptor-specific agonist (SKF-38393
      or quinpirole), a non-specific DA agonist (apomorphine), or a control Ringer's
      solution, and vocalizations were recorded after a 20 min post-injection period.
      Behavioral analyses focused on if and when the frogs called (call latency), and
      the number of calls produced during post-injection recordings (call rate). There
      were significant differences in all measurements that varied with treatment
      and/or dose. The results demonstrate that activation of D2-like receptors has an
      inhibitory effect on vocalization in the green tree frog, while the D1-like and
      non-specific DA agonists do not affect calling behavior. These findings coincide
      with behavioral data from other taxa, and support the function of D2-like
      receptors in the inhibition of certain social behaviors. Overall, the results
      suggest conservation for DA in social behaviors across vertebrates.

PMID- 23531472
TI  - Does monosodium glutamate interact with macronutrient composition to influence
      subsequent appetite?
AB  - The influence of flavour enhancers such as monosodium glutamate (MSG) on
      satiation and satiety is unclear, and the present study aimed to explore this by
      examining the effects consumption of soups varying in MSG (1% MSG added or no
      MSG) and macronutrient content (added carbohydrate, protein or control) had on
      appetite. 24 non-obese, low-restraint male participants consumed a fixed portion
      of soup and rated their appetite before, immediately after intake and at 15
      minute intervals for 120 min post-ingestion across six sessions. Added MSG
      significantly increased flavour pleasantness and tended to result in a smaller
      decrease in hunger immediately after soup ingestion. MSG also reduced rather than
      enhanced feelings of fullness immediately after ingestion of the high protein
      soup. As expected, hunger increased, and fullness decreased, over the subsequent
      120 min, but the increase in hunger was significantly lower in the MSG than no
      MSG conditions with the protein soup between 30 and 60 min post-ingestion.
      Overall these data suggest that MSG may have a bi-phasic effect on appetite, with
      reduced satiation mediated by effects on palatability, but potential for enhanced
      post-ingestive satiety particularly in the context of protein ingestion.

PMID- 23531473
TI  - Salivary testosterone is related to self-selected training load in elite female
      athletes.
AB  - BACKGROUND: Testosterone has been related to improved acute neuromuscular
      performance in athletic populations. It is our contention that testosterone may
      also contribute to improved volitional motivation and, when monitored
      longitudinally, may provide one proxy marker for readiness to perform. METHODS:
      Twelve female netball players provided saliva samples prior to five standardized
      training sessions in which they completed a maximal-distance medicine ball throw,
      and then 3 sets of bench press and then back squat using a self-selected load
      perceived to equal a 3-repetition maximum load. Additional repetitions were
      encouraged when possible and total voluntary workload was calculated from the
      product of the load lifted and repetitions performed. RESULTS: Relative salivary
      testosterone levels as a group were correlated with bench press (r=0.8399;
      p=0.0007) and squat (r=0.6703; p=0.0171) self-selected workload, as well as
      maximal medicine ball throw performance (r=0.7062; p=0.0103). CONCLUSIONS:
      Individual salivary testosterone, when viewed relatively over time, demonstrated
      strong relationships with self-selected workloads during an in-season training
      period in female netball players. As such, daily variations in testosterone may
      provide information regarding voluntary training motivation and readiness to
      perform in elite athletic populations. Psychological and behavioral aspects of
      testosterone may have the potential to enhance training adaptation by
      complementing the known anabolic and permissive properties of testosterone.

PMID- 23531474
TI  - Fimbria-fornix and entorhinal cortex differential contribution to contextual and
      cued fear conditioning consolidation in rats.
AB  - The Fimbria-Fornix (FF) and Entorhinal Cortex (EC) are the primary interfaces
      between the hippocampus and, respectively, subcortical structures and cortical
      areas. Their mnemonic role has been repeatedly proposed. In order to investigate
      their role in fear conditioning, FF and EC were subjected to bilateral fully
      reversible tetrodotoxin (TTX) inactivation during consolidation in adult male
      Wistar rats that had undergone training for fear conditioning to an acoustic
      stimulus (CS) and context. TTX was stereotaxically injected into animals of
      different groups at increasing post-acquisition delays. Memory was assessed as
      conditioned freezing duration measured during retention testing, performed 72 and
      96 h after TTX administration in a counterbalanced manner. The results showed
      that FF inactivation, performed immediately after conditioning, did not disrupt
      consolidation of either contextual or auditory fear memory. On the contrary, EC
      inactivation performed at the same time was followed by both contextual and CS
      fear response retention impairment. EC inactivation performed 1.5h post
      acquisition impaired only contextual fear response retention. EC inactivation
      performed 24h after acquisition training had no effect on the consolidation
      process. The present findings show a clearly different role of FF and EC in fear
      conditioning consolidation in the rat. The results are discussed in relation to
      their known connections with the hippocampus.

PMID- 23531475
TI  - Variability in infant acute pain responding meaningfully obscured by averaging
      pain responses.
AB  - Given the inherent variability in pain responding, using an "average" pain score
      may pose serious threats to internal and external validity. Using growth mixture
      modeling (GMM), this article first examines whether infants can be differentiated
      into stable groups based on their pain response patterns over a 2-minute post
      needle period. Secondary analyses, to specifically address the issue of averaging
      pain scores to represent a sample, qualitatively described clinically meaningful
      differences between pain scores of the discerned groups and the overall mean
      (irrespective of groups). Infants were part of Canadian longitudinal cohort
      naturalistically observed during their 2-, 4-, 6-, and/or 12-month immunization
      appointments (N=458 to 574) at 3 pediatrician clinics between 2007 and 2012. At
      every age, GMM analyses discerned distinct groups of infants with significantly
      variable patterns of pain responding over the 2minutes post-needle. Our secondary
      suggested that the overall mean pain score immediately post-needle reflected most
      groups well at every age. However, for older infants (6 and 12months,
      especially), the overall mean pain responses at 1 and 2minutes post-needle
      significantly over or underestimated groups that contained 48% to 100% of the
      sample. These results combined highlight the significant variability of infant
      pain responding patterns between groups of infants and furthermore, calls into
      question the validity of using an overall mean in research with older infants
      during the regulatory phase post-needle.

PMID- 23531477
TI  - Letter to the editor in response to 'Low-dose metabolism of benzene in humans:
      science and obfuscation' Rappaport et al. (2013).

PMID- 23531476
TI  - Preclinical episodes of orofacial pain symptoms and their association with health
      care behaviors in the OPPERA prospective cohort study.
AB  - The course of preclinical pain symptoms sheds light on the etiology and prognosis
      of chronic pain. We aimed to quantify rates of developing initial and recurrent
      symptoms of painful temporomandibular disorder (TMD) and to evaluate associations
      with health behaviors. In the OPPERA prospective cohort study, 2,719 individuals
      aged 18 to 44years with lifetime absence of TMD when enrolled completed 25,103
      quarterly (3-monthly) questionnaires during a median 2.3-year follow-up period.
      Questionnaires documented TMD symptom episodes, headache, other body pain, health
      care attendance, and analgesic use, and. Kaplan-Meier methods for clustered data
      estimated symptom-free survival time. Multivariable models assessed demographic
      variation in TMD symptom rates and evaluated associations with health care and
      analgesic use. One-third of the study subjects developed TMD symptoms and for a
      quarter of symptomatic episodes, pain intensity was severe. Initial TMD symptoms
      developed at an annual rate of 18.8 episodes per 100 persons. The annual rate
      more than doubled for first-recurrence and doubled again for second or subsequent
      recurrence such that, 1year after first recurrence, 71% of study subjects
      experienced a second recurrence. The overall rate increased with age and was
      greater in African Americans and lower in Asians relative to those of white
      race/ethnicity. The probability of TMD symptoms was strongly associated with
      concurrent episodes of headache and body pain and with past episodes of TMD
      symptoms. Episodes of TMD symptoms, headache, and body pain were associated with
      increases of ~10% in probability of analgesic use and health care attendance.
      Yet, even when TMD, headache, and body pain occurred concurrently, 27% of study
      subjects neither attended health care nor used analgesics.

PMID- 23531478
TI  - The "Test Your Memory" test performs better than the MMSE in a population without
      known cognitive dysfunction.
AB  - AIM: To examine the relation of performance on the self-administered Test Your
      Memory test (TYM) and the Mini-Mental State Examination (MMSE) with a
      comprehensive neuropsychological assessment in a population sample including
      people with modest cognitive decrements. METHODS: Eighty-six participants (aged
      56-77 years), without known cognitive dysfunction, performed a neuropsychological
      assessment including MMSE, and were asked to fill out the TYM. The relation
      between both the TYM and the MMSE and a neuropsychological assessment was
      examined by means of correlation analyses, area under the ROC curves for
      discriminating between a "normal" and "modest decrements"(>=1SD below the sample
      mean) group, and Bland-Altman plots. RESULTS: Correlation with the full
      neuropsychological assessment was significantly stronger for the TYM than the
      MMSE (r=0.78 versus r=0.55; Steiger's Z=2.66, p<0.01). The TYM showed an area
      under the ROC-curve of 0.88 (95% CI 0.80 to 0.97) for differentiating between
      "normal" and "modest decrements" compared with 0.71 (0.53 to 0.90) for the MMSE.
      Bland-Altman plots showed limits of agreement for the TYM of -1.10 to 1.10 and
      for the MMSE of -1.39 to 1.38. CONCLUSIONS: The TYM showed good correlation with
      a neuropsychological assessment, performed better in discriminating between
      variations of cognition and showed more agreement with a neuropsychological
      assessment than the MMSE.

PMID- 23531479
TI  - Regulatory T cells contribute to rosuvastatin-induced cardioprotection against
      ischemia-reperfusion injury.
AB  - OBJECTIVES: CD4CD25 regulatory T cells (Tregs) play a key role in the prevention
      of various inflammatory and autoimmune disorders by suppressing immune responses.
      The beneficial effect of statins on myocardial ischemia-reperfusion injury (IRI)
      depends in part on their immunomodulatory and anti-inflammatory mechanisms. We
      aimed to determine whether Tregs contribute to statin-induced cardioprotection
      against myocardial IRI. METHODS: Thirty-two rats were divided into four groups:
      sham, ischemia-reperfusion (IR), rosuvastatin (RSV)/IR, and mevalonic acid
      (MVA)+RSV/IR. Myocardial IR was induced by a 30-min coronary occlusion, followed
      by a 48-h reperfusion. RSV (5 mg/kg) was administered intravenously 18 h before
      IR. The rats were killed after 48-h reperfusion. Serum cardiac troponin I (cTnI)
      was measured by ELISA, infiltration of inflammatory cells in myocardium by
      hematoxylin and eosin staining, expression of FoxP3 protein by western blotting,
      accumulation of Tregs in myocardium by immunohistochemical examination, and
      infarct size by TTC staining. RESULTS: Significant elevation in serum cTnI,
      enlarged infarct size, and marked infiltration of inflammatory cells in
      myocardium were observed in the IR group. The administration of RSV significantly
      reduced the serum cTnI level, attenuated the accumulation of inflammatory cells,
      decreased infarct size, and increased the FoxP3 expression and Treg accumulation
      in myocardium compared with the IR group. The combination of RSV and MVA
      pretreatment partially abolished the anti-inflammatory and infarct size-limiting
      effects and completely reversed Treg accumulation in myocardium induced by RSV.
      The accumulation of inflammatory cells was negatively correlated with FoxP3
      expression and Treg accumulation in the ischemic myocardium. CONCLUSION: RSV
      pretreatment was associated with more Treg accumulation, less inflammatory
      response, and myocardial injury, suggesting that such cardioprotection against
      IRI was partially mediated by Treg-negative modulation of inflammation response,
      probably through the HMG-CoA reductase pathway.

PMID- 23531480
TI  - Thrombin generation and microparticles in inflammatory bowel diseases.

PMID- 23531481
TI  - Allogeneic hematopoietic stem cell transplantation may restore gluten tolerance
      in patients with celiac disease.
AB  - We report on 2 patients affected by both celiac disease (CD) and beta-thalassemia
      major who underwent successful myeloablative allogeneic hematopoietic stem cell
      transplantation (HSCT) for the latter condition. After HSCT, the introduction of
      a gluten-containing diet did not cause the reappearance of clinical, serological,
      and histological markers of CD in up to 5 years of follow-up. After
      transplantation, in both patients, dendritic cells and regulatory FoxP3T cells
      showed a recovery of normal values and no proliferative T-cell response upon
      gliadin stimulation was found. These data suggest that allogeneic HSCT may lead
      to induction of gluten tolerance in patients with CD.

PMID- 23531482
TI  - The hCMEC/D3 cell line as a model of the human blood brain barrier.
AB  - Since the first attempts in the 1970s to isolate cerebral microvessel endothelial
      cells (CECs) in order to model the blood-brain barrier (BBB) in vitro, the need
      for a human BBB model that closely mimics the in vivo phenotype and is
      reproducible and easy to grow, has been widely recognized by cerebrovascular
      researchers in both academia and industry. While primary human CECs would ideally
      be the model of choice, the paucity of available fresh human cerebral tissue
      makes wide-scale studies impractical. The brain microvascular endothelial cell
      line hCMEC/D3 represents one such model of the human BBB that can be easily grown
      and is amenable to cellular and molecular studies on pathological and drug
      transport mechanisms with relevance to the central nervous system (CNS). Indeed,
      since the development of this cell line in 2005 over 100 studies on different
      aspects of cerebral endothelial biology and pharmacology have been published.
      Here we review the suitability of this cell line as a human BBB model for
      pathogenic and drug transport studies and we critically consider its advantages
      and limitations.

PMID- 23531483
TI  - Who rises to the top? Early indicators.
AB  - Youth identified before age 13 (N = 320) as having profound mathematical or
      verbal reasoning abilities (top 1 in 10,000) were tracked for nearly three
      decades. Their awards and creative accomplishments by age 38, in combination with
      specific details about their occupational responsibilities, illuminate the
      magnitude of their contribution and professional stature. Many have been
      entrusted with obligations and resources for making critical decisions about
      individual and organizational well-being. Their leadership positions in business,
      health care, law, the professoriate, and STEM (science, technology, engineering,
      and mathematics) suggest that many are outstanding creators of modern culture,
      constituting a precious human-capital resource. Identifying truly profound human
      potential, and forecasting differential development within such populations,
      requires assessing multiple cognitive abilities and using atypical measurement
      procedures. This study illustrates how ultimate criteria may be aggregated and
      longitudinally sequenced to validate such measures.

PMID- 23531484
TI  - NASA faked the moon landing--therefore, (climate) science is a hoax: an anatomy
      of the motivated rejection of science.
AB  - Although nearly all domain experts agree that carbon dioxide emissions are
      altering the world's climate, segments of the public remain unconvinced by the
      scientific evidence. Internet blogs have become a platform for denial of climate
      change, and bloggers have taken a prominent role in questioning climate science.
      We report a survey of climate-blog visitors to identify the variables underlying
      acceptance and rejection of climate science. Our findings parallel those of
      previous work and show that endorsement of free-market economics predicted
      rejection of climate science. Endorsement of free markets also predicted the
      rejection of other established scientific findings, such as the facts that HIV
      causes AIDS and that smoking causes lung cancer. We additionally show that, above
      and beyond endorsement of free markets, endorsement of a cluster of conspiracy
      theories (e.g., that the Federal Bureau of Investigation killed Martin Luther
      King, Jr.) predicted rejection of climate science as well as other scientific
      findings. Our results provide empirical support for previous suggestions that
      conspiratorial thinking contributes to the rejection of science. Acceptance of
      science, by contrast, was strongly associated with the perception of a consensus
      among scientists.

PMID- 23531485
TI  - Increasing recognition of happiness in ambiguous facial expressions reduces anger
      and aggressive behavior.
AB  - The ability to identify emotion in other people is critical to social
      functioning. In a series of experiments, we explored the relationship between
      recognition of emotion in ambiguous facial expressions and aggressive thoughts
      and behavior, both in healthy adults and in adolescent youth at high risk of
      criminal offending and delinquency. We show that it is possible to experimentally
      modify biases in emotion recognition to encourage the perception of happiness
      over anger in ambiguous expressions. This change in perception results in a
      decrease in self-reported anger and aggression in healthy adults and high-risk
      youth, respectively, and also in independently rated aggressive behavior in high
      risk youth. We obtained similar effects on mood using two different techniques to
      modify biases in emotion perception (feedback-based training and visual
      adaptation). These studies provide strong evidence that emotion processing plays
      a causal role in anger and the maintenance of aggressive behavior.

PMID- 23531487
TI  - Brain anatomy of autism spectrum disorders I. Focus on corpus callosum.
AB  - This brief review aims to examine the structural magnetic resonance imaging
      (sMRI) studies on corpus callosum in autism spectrum disorders (ASD) and discuss
      the clinical and demographic factors involved in the interpretation of results. 

PMID- 23531486
TI  - The wear and tear of daily stressors on mental health.
AB  - Researchers assert that affective responses to seemingly minor daily events have
      long-term implications for mental health, yet this phenomenon has rarely been
      investigated. In the current study, we examined how levels of daily negative
      affect and affective reactivity in response to daily stressors predicted general
      affective distress and self-reported anxiety and depressive disorders 10 years
      after they were first assessed. Across eight consecutive evenings, participants
      (N = 711; age = 25 to 74 years) reported their daily stressors and their daily
      negative affect. Increased levels of negative affect on nonstressor days were
      related to general affective distress and symptoms of an affective disorder 10
      years later. Heightened affective reactivity to daily stressors predicted greater
      general affective distress and an increased likelihood of reporting an affective
      disorder. These findings suggest that the average levels of negative affect that
      people experience and how they respond to seemingly minor events in their daily
      lives have long-term implications for their mental health.

PMID- 23531488
TI  - Transport function and transcriptional regulation of a liver-enriched human
      organic anion transporting polypeptide 2B1 transcriptional start site variant.
AB  - Human organic anion transporting polypeptide 2B1 (OATP2B1) is a membrane
      transporter that facilitates the cellular uptake of a number of endogenous
      compounds and drugs. OATP2B1 is widely expressed in tissues including the small
      intestine, liver, kidney, placenta, heart, skeletal muscle, and platelets. It was
      recently shown that differential promoter usage in tissues results in expression
      of five OATP2B1 transcriptional start site variants that use distinct first exons
      but share common subsequent exons. These variants are expected to encode either a
      full-length (OATP2B1-FL) or shortened protein lacking 22 N terminus amino acids
      (OATP2B1-Short). Little is known regarding the transport activity and regulation
      of OATP2B1 variants with N terminus truncation. Here, using absolute quantitative
      polymerase chain reaction, we find the full-length variant is the major form
      expressed in duodenum but the short variant predominates in liver. Using a
      transient heterologous cell expression system, we find that the transport
      activities of the short OATP2B1 variant toward substrates estrone sulfate and
      rosuvastatin are similar to the well characterized full-length variant.
      Transcriptional activity screening of the liver-enriched OATP2B1 variant promoter
      identified hepatocyte nuclear factor 4 alpha (HNF4alpha) as a novel transacting
      factor. With a combination of in silico screening, promoter mutation in cell
      based reporter assays, small interfering RNA knockdown, and chromatin
      immunoprecipitation (ChIP) studies, we identified a functional HNF4alpha binding
      site close to the transcription start site (-17 to -4 bp). We conclude that the
      major OATP2B1 protein form in liver is transport competent and its hepatic
      expression is regulated by HNF4alpha.

PMID- 23531490
TI  - Management of occupational exposure to engineered nanoparticles through a chance
      constrained nonlinear programming approach.
AB  - Critical environmental and human health concerns are associated with the rapidly
      growing fields of nanotechnology and manufactured nanomaterials (MNMs). The main
      risk arises from occupational exposure via chronic inhalation of nanoparticles.
      This research presents a chance-constrained nonlinear programming (CCNLP)
      optimization approach, which is developed to maximize the nanaomaterial
      production and minimize the risks of workplace exposure to MNMs. The CCNLP method
      integrates nonlinear programming (NLP) and chance-constrained programming (CCP),
      and handles uncertainties associated with both the nanomaterial production and
      workplace exposure control. The CCNLP method was examined through a single-walled
      carbon nanotube (SWNT) manufacturing process. The study results provide optimal
      production strategies and alternatives. It reveal that a high control measure
      guarantees that environmental health and safety (EHS) standards regulations are
      met, while a lower control level leads to increased risk of violating EHS
      regulations. The CCNLP optimization approach is a decision support tool for the
      optimization of the increasing MNMS manufacturing with workplace safety
      constraints under uncertainties.

PMID- 23531489
TI  - Climate change is likely to worsen the public health threat of diarrheal disease
      in Botswana.
AB  - Diarrheal disease is an important health challenge, accounting for the majority
      of childhood deaths globally. Climate change is expected to increase the global
      burden of diarrheal disease but little is known regarding climate drivers,
      particularly in Africa. Using health data from Botswana spanning a 30-year period
      (1974-2003), we evaluated monthly reports of diarrheal disease among patients
      presenting to Botswana health facilities and compared this to climatic variables.
      Diarrheal case incidence presents with a bimodal cyclical pattern with peaks in
      March (ANOVA p < 0.001) and October (ANOVA p < 0.001) in the wet and dry season,
      respectively. There is a strong positive autocorrelation (p < 0.001) in the
      number of reported diarrhea cases at the one-month lag level. Climatic variables
      (rainfall, minimum temperature, and vapor pressure) predicted seasonal diarrheal
      with a one-month lag in variables (p < 0.001). Diarrheal case incidence was
      highest in the dry season after accounting for other variables, exhibiting on
      average a 20% increase over the yearly mean (p < 0.001). Our analysis suggests
      that forecasted climate change increases in temperature and decreases in
      precipitation may increase dry season diarrheal disease incidence with hot, dry
      conditions starting earlier and lasting longer. Diarrheal disease incidence in
      the wet season is likely to decline. Our results identify significant health
      climate interactions, highlighting the need for an escalated public health focus
      on controlling diarrheal disease in Botswana. Study findings have application to
      other arid countries in Africa where diarrheal disease is a persistent public
      health problem.

PMID- 23531491
TI  - The influence of urban natural and built environments on physiological and
      psychological measures of stress--a pilot study.
AB  - Environments shape health and well-being, yet little research has investigated
      how different real-world environmental settings influence the well-known
      determinant of health known as stress. Using a cross-over experimental design;
      this pilot study investigated the effect of four urban environments on
      physiological and psychological stress measures. Participants (N = 15) were
      exposed on separate days to one of the four settings for 20 min. These settings
      were designated as Very Natural; Mostly Natural; Mostly Built and Very Built.
      Visitation order to the four settings was individually randomized. Salivary
      cortisol and alpha-amylase; as well as self-report measures of stress; were
      collected before and after exposure to each setting. Gender was included as a
      variable in analysis; and additional data about environmental self-identity, pre
      existing stress, and perceived restorativeness of settings were collected as
      measures of covariance. Differences between environmental settings showed greater
      benefit from exposure to natural settings relative to built settings; as measured
      by pre-to-post changes in salivary amylase and self-reported stress; differences
      were more significant for females than for males. Inclusion of covariates in a
      regression analysis demonstrated significant predictive value of perceived
      restorativeness on these stress measures, suggesting some potential level of
      mediation. These data suggest that exposure to natural environments may warrant
      further investigation as a health promotion method for reducing stress.

PMID- 23531492
TI  - Nature appropriation and associations with population health in Canada's largest
      cities.
AB  - Earth is a finite system with a limited supply of resources. As the human
      population grows, so does the appropriation of Earth's natural capital, thereby
      exacerbating environmental concerns such as biodiversity loss, increased
      pollution, deforestation and global warming. Such concerns will negatively impact
      human health although it is widely believed that improving socio-economic
      circumstances will help to ameliorate environmental impacts and improve health
      outcomes. However, this belief does not explicitly acknowledge the fact that
      improvements in socio-economic position are reliant on increased inputs from
      nature. Gains in population health, particularly through economic means, are
      disconnected from the appropriation of nature to create wealth so that health
      gains become unsustainable. The current study investigated the sustainability of
      human population health in Canada with regard to resource consumption or
      "ecological footprints" (i.e., the resources required to sustain a given
      population). Ecological footprints of the 20 largest Canadian cities, along with
      several important determinants of health such as income and education, were
      statistically compared with corresponding indicators of human population health
      outcomes. A significant positive relationship was found between ecological
      footprints and life expectancy, as well as a significant negative relationship
      between ecological footprints and the prevalence of high blood pressure. Results
      suggest that increased appropriation of nature is linked to improved health
      outcomes. To prevent environmental degradation from excessive appropriation of
      natural resources will require the development of health promotion strategies
      that are de-coupled from ever-increasing and unsustainable resource use. Efforts
      to promote population health should focus on health benefits achieved from a
      lifestyle based on significantly reduced consumption of natural resources.

PMID- 23531493
TI  - Repetitive transforaminal steroid injections in cervical radiculopathy: a
      prospective outcome study including 140 patients.
AB  - STUDY DESIGN:  Prospective case series. OBJECTIVE:  To evaluate the effect of
      three repetitive transforaminal steroid injections in a large series of selected
      patients with cervical radiculopathy caused by spondylosis. METHODS: 
      Consecutively, 140 patients with long-lasting medical history, clinical findings,
      and MRI indicating a cervical nerve root origin based on degenerative disease and
      a positive selective transforaminal diagnostic nerve root blocks with local
      anesthetics resulting in at least 50% temporary arm pain reduction were included.
      Before treatment started, patients underwent a clinical examination by a
      neurosurgeon. All patients were followed-up and evaluated by one physiotherapist
      at the neurosurgery outpatient clinic. A designed outcome questionnaire including
      Neck Disability Index (NDI), Symptoms Frequency Index, and Visual Analog Scale
      for pain intensity were used. A series of three transforaminal steroid
      injections, with 3 weeks in between, were performed by a neuroradiologist using
      image intensifier guidance in an x-ray suite. At 12-14 weeks after the first
      injection, follow-up was performed. Criteria for positive response to the
      treatment was >50% radicular arm pain reduction. Except for occasional
      painkillers, no other treatment was given to the patients. RESULTS:  Positive
      response to the treatment was achieved in 49% (n = 69) with a significant
      difference in NDI and pain intensity between responders and nonresponders.
      CONCLUSIONS:  Repetitive transforaminal steroid injections may reduce symptoms
      (frequency, intensity, and fewer limitations of daily living activities) of
      radiculopathy in patients with degenerative disease in the cervical spine at a
      short time follow-up. [Table: see text].

PMID- 23531494
TI  - Post-traumatic epilepsy with isolated memory flashbacks.
AB  - Some traumatic events can cause both post-traumatic stress disorder and epileptic
      seizures. We report the case of a woman who experienced a severe head injury
      which subsequently led to the development of paroxysmal episodes of isolated
      memory flashbacks related to the injury. Detailed analysis of her symptoms along
      with video-EEG telemetry recordings was helpful to distinguish between these two
      conditions. [Published with video sequences].

PMID- 23531495
TI  - A Further Study of the Role of Copper in Regard to the Antimutagenic Action of
      Sodium Copper Chlorophyllin (SCC) in Somatic Cells of Drosophila melanogaster.
AB  - Previous findings suggest that copper plays a crucial role in the antimutagenic
      effect of sodium copper chlorophyllin (SCC). The objective of the current
      research was to compare the antimutagenic effects of two SCC compounds with
      different amounts of copper (3.7% and 5.4%, respectively) on the genetic damage
      induced by gamma rays in somatic cells of Drosophila. Data indicate that an
      increase in copper content of 31.5% in SCC-5.4 resulted in a greater inhibition
      of gamma ray genetic damage of 49% whereas only a 2% inhibition with SCC-3.7
      occurred. Of greater interest is the association of SCC with a variety of uses in
      humans, such as a chemo preventive agent and food supplement. A greater attention
      to the concentration of copper in the SCC product in use should be required.

PMID- 23531497
TI  - Radiocesium concentrations in the bark, sapwood and heartwood of three tree
      species collected at Fukushima forests half a year after the Fukushima Dai-ichi
      nuclear accident.
AB  - Radiocesium ((134)Cs and (137)Cs) distribution in tree stems of Japanese cedar
      (aged 40-56 y), red pine (42 y), and oak (42 y) grown in Fukushima Prefecture
      were investigated approximately half a year after the Fukushima Dai-ichi nuclear
      accident. Japanese cedar, red pine, and oak were selected from five sites, one
      site, and one site, respectively. Three trees at each site were felled, and bark,
      sapwood (the outer layer of wood in the stem), and heartwood (the inner layer of
      wood in the stem) separately collected to study radiocesium concentrations
      measured by gamma-ray spectrometry. The radiocesium deposition densities at the
      five sites were within the range of 16-1020 kBq m(-2). The radiocesium was
      distributed in bark, sapwood, and heartwood in three tree species, indicating
      that very rapid translocation of radiocesium into the wood. The concentration of
      radiocesium in oak (deciduous angiosperm) bark was higher than that in the bark
      of Japanese cedar and red pine (evergreen gymnosperms). Both sapwood and
      heartwood contained radiocesium, and the values were much lower than that in the
      bark samples. The results suggest that radiocesium contamination half a year
      after the accident was mainly attributable to the direct radioactive deposition.
      The radiocesium concentrations in the Japanese cedar samples taken from five
      sites rose with the density of radiocesium accumulation on the ground surface. To
      predict the future dynamics of radiocesium in tree stems, the present results
      taken half a year after the accident are important, and continuous study of
      radiocesium in tree stems is necessary.

PMID- 23531496
TI  - Multiple sensors ensure guide strand selection in human RNAi pathways.
AB  - Small RNAs guide RNA-induced silencing complexes (RISCs) to bind to cognate mRNA
      transcripts and trigger silencing of protein expression during RNA interference
      (RNAi) in eukaryotes. A fundamental aspect of this process is the asymmetric
      loading of one strand of a short interfering RNA (siRNA) or microRNA (miRNA)
      duplex onto RISCs for correct target recognition. Here, we use a reconstituted
      system to determine the extent to which the core components of the human RNAi
      machinery contribute to RNA guide strand selection. We show that Argonaute2
      (Ago2), the endonuclease that binds directly to siRNAs and miRNAs within RISC,
      has intrinsic but substrate-dependent RNA strand selection capability. This
      activity can be enhanced substantially when Ago2 is in complex with the
      endonuclease Dicer and the double-stranded RNA-binding proteins (dsRBPs)-trans
      activation response (TAR) RNA-binding protein (TRBP) or protein activator of PKR
      (PACT). The extent to which human Dicer/dsRBP complexes contribute to strand
      selection is dictated by specific duplex parameters such as thermodynamics, 5'
      nucleotide identity, and structure. Surprisingly, our results also suggest that
      strand selection for some miRNAs is enhanced by PACT-containing complexes but not
      by those containing TRBP. Furthermore, overall mRNA targeting by miRNAs is
      disfavored for complexes containing TRBP but not PACT. These findings demonstrate
      that multiple proteins collaborate to ensure optimal strand selection in humans
      and reveal the possibility of delineating RNAi pathways based on the presence of
      TRBP or PACT.

PMID- 23531499
TI  - A vascular complication in computer navigated total knee arthroplasty.
AB  - The use of computer navigation has the potential to improve implant position in
      total knee arthroplasty (TKA), but pin fixation of reference arrays introduces an
      additional potential source of complications. We report a case of vascular injury
      related to the insertion of a femoral pin during navigated TKA.

PMID- 23531498
TI  - Hepatic disposal of advanced glycation end products during maturation and aging.
AB  - Aging is characterized by progressive loss of metabolic and biochemical functions
      and accumulation of metabolic by-products, including advanced glycation end
      products (AGEs), which are observed in several pathological conditions. A number
      of waste macromolecules, including AGEs are taken up from the circulation by
      endocytosis mainly into liver sinusoidal endothelial cells (LSECs) and Kupffer
      cells (KCs). However, AGEs still accumulate in different tissues with aging,
      despite the presence of this clearance mechanism. The aim of the present study
      was to determine whether the efficiency of LSECs and KCs for disposal of AGEs
      changes through aging. RESULTS: After intravenous administration of (14)C-AGE
      albumin in pre-pubertal, young adult, middle aged and old mice, more than 90% of
      total recovered (14)C-AGE was liver associated, irrespective of age. LSECs and
      KCs represented the main site of uptake. A fraction of the (14)C-AGE degradation
      products ((14)C-AGE-DPs) was stored for months in the lysosomes of these cells
      after uptake. The overall rate of elimination of (14)C-AGE-DPs from the liver was
      markedly faster in pre-pubertal than in all post-pubertal age groups. The ability
      to eliminate (14)C-AGE-DPs decreased to similar extents after puberty in LSECs
      and KCs. A rapid early removal phase was characteristic for all age groups except
      the old group, where this phase was absent. CONCLUSIONS: Removal of AGE-DPs from
      the liver scavenger cells is a very slow process that changes with age. The
      ability of these cells to dispose of AGEs declines after puberty. Decreased AGE
      removal efficiency early in life may lead to AGE accumulation.

PMID- 23531500
TI  - Changes of the enteric nervous system in amyloid-beta protein precursor
      transgenic mice correlate with disease progression.
AB  - In Alzheimer's disease (AD), fatal neuronal cell loss occurs long before relevant
      evidence can lead to a reliable diagnosis. If characteristic pathological
      alterations take place in the enteric nervous system (ENS), it could be one of
      the most promising targets for an early diagnosis, using submucosal biopsies from
      the gut. We therefore investigated time- and spatial-dependent changes in an
      amyloid-beta protein precursor (AbetaPP) overexpressing transgenic mouse model to
      examine early changes within the ENS. Wholemount preparations and paraffin
      sections were analyzed for the expression of neuronal, glial, and innate immunity
      markers. Isolated myenteric networks were screened for differences in overall
      protein expression, and a motility analysis delivered functional data. The level
      of AbetaPP in the gut was significantly higher in the AD mouse model than in wild
      type mice and also higher in the gut than in the brain at all ages investigated.
      The transcriptional level of Nestin, GFAP, and TLR4 increased with age with a
      peak at 3 months. At the protein level, human amyloid-beta was located in
      myenteric neurons. Myenteric networks showed a reduction of the neuronal density
      in AbetaPP compared to wild-type mice, which was functionally relevant as
      revealed by motility analysis. The ENS undergoes significant changes during the
      early onset of AbetaPP expression in AD mouse models that appear before those
      seen in the brain as demonstrated in this study. Thus, there is a chance of
      determining similar alterations in the human gut of AD patients, which could be
      used to develop early diagnostic approaches.

PMID- 23531501
TI  - Identification of a novel complex AbetaPP:Fe65:PP1 that regulates AbetaPP Thr668
      phosphorylation levels.
AB  - The amyloid-beta protein precursor (AbetaPP) binds several proteins determining
      metabolism, processing, and the physiological fate of the former. Among these is
      Fe65, a protein with specific functional significance for AbetaPP, in particular
      conferring stability when the latter is dephosphorylated on Thr668. Thus, it
      follows that phosphatases like protein phosphatase 1 (PP1) are relevant to
      AbetaPP processing. Consequently, the identification of AbetaPP binding proteins,
      which can be modulated directly or indirectly by PP1, take on added relevance in
      terms of biological significance. Using the yeast tri-hybrid system and co
      immunoprecipitation assays, we describe a novel tri-complex comprising AbetaPP,
      Fe65 and PP1. We show that the trimeric complex (AbetaPP:Fe65:PP1gamma) occurs in
      COS-7 cells, rat hippocampal and cortical primary neurons, and in adult rat
      hippocampus and cortex. Using overlay assays, we demonstrate that Fe65 is in fact
      the bridging protein in the complex formed and thus we simultaneously describe
      another PP1 binding protein. This is singularly important given that PP1 binding
      proteins determine and confer subcellular localization, as well as substrate
      specificity, thus regulating the phosphatase activity and subsequent
      intracellular events. Additionally, we show that this interaction correlates with
      AbetaPP Thr668 phosphorylation state, consistent with the role of protein
      (de)phosphorylation as a key mechanism in regulating cellular events.

PMID- 23531502
TI  - Interaction of cinnamaldehyde and epicatechin with tau: implications of
      beneficial effects in modulating Alzheimer's disease pathogenesis.
AB  - Abnormal modifications in tau such as hyperphosphorylation, oxidation, and
      glycation interfere with its interaction with microtubules leading to its
      dissociation and self-aggregation into neurofibrillary tangles, a hallmark of
      Alzheimer's disease (AD). Previously we reported that an aqueous extract of
      cinnamon has the ability to inhibit tau aggregation in vitro and can even induce
      dissociation of tangles isolated from AD brain. In the present study, we carried
      out investigations with cinnamaldehyde (CA) and epicatechin (EC), two components
      of active cinnamon extract. We found that CA and the oxidized form of EC (ECox)
      inhibited tau aggregation in vitro and the activity was due to their interaction
      with the two cysteine residues in tau. Mass spectrometry of a synthetic peptide,
      SKCGS, representing the actual tau sequence, identified the thiol as reacting
      with CA and ECox. Use of a cysteine double mutant of tau showed the necessity of
      cysteine for aggregation inhibition by CA. The interaction of CA with tau
      cysteines was reversible and the presence of CA did not impair the biological
      function of tau in tubulin assembly in vitro. Further, these compounds protected
      tau from oxidation caused by the reactive oxygen species, H2O2, and prevented
      subsequent formation of high molecular weight species that are considered to
      stimulate tangle formation. Finally, we observed that EC can sequester highly
      reactive and toxic byproducts of oxidation such as acrolein. Our results suggest
      that small molecules that form a reversible interaction with cysteines have the
      potential to protect tau from abnormal modifications.

PMID- 23531510
TI  - Use of computed tomography to predict union and time to union in acute scaphoid
      fractures treated nonoperatively.
AB  - PURPOSE: To use computed tomography to determine whether factors could be
      identified to predict union for acute scaphoid fractures treated nonoperatively.
      METHODS: We used a radiology database at a tertiary care center to identify
      scaphoid computed tomography scans performed between 2004 and 2010. We noted
      fracture location, fracture orientation, translation between fragments, humpback
      deformity, comminution, cysts, and sclerosis. We determined the associations
      between imaging variables on union rates and time to achieve union with casting
      alone in a cohort of 219 patients (mean age, 31 y; 83% males). RESULTS: Most
      fractures were scaphoid waist fractures (173 of 219; 79%), of which 178 (81% of
      total group) were nondisplaced. There were 28 proximal pole fractures (13%) and
      18 distal pole fractures (8%). The overall union rate was 95% (207 of 219). The
      odds of developing a nonunion were increased in fractures with translation (odds
      ratio, 3.4) or with a humpback deformity (odds ratio, 6.9). The presence of
      sclerosis or cysts did not correlate with union rates. There was no statistical
      association between successful union and fracture location, although, given the
      small number of proximal pole fractures, we were underpowered for this finding.
      Time to union was longer for proximal pole fractures (113 d) versus distal pole
      (53 d) and waist fractures (65 d) and for fractures with sclerosis (166 vs 67 d)
      or comminution (103 vs 66 d). CONCLUSIONS: We were able to identify a number of
      features that contributed to risk of nonunion or delayed union based on computed
      tomography scan. Factors such as fracture translation, comminution, and humpback
      were related to a higher risk of scaphoid nonunion. Factors such as sclerosis,
      comminution, translation, and location in the proximal pole were associated with
      longer times to union. These variables were independently significant in
      increasing the time required to achieve union and were shown to have an overall
      additive effect. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 23531511
TI  - A study of recipient related predictors of success in oocyte donation program.
AB  - BACKGROUND: Oocyte donation is an invaluable therapy for couples with impending
      or complete ovarian failure. In addition, oocyte donation affords a scientific
      opportunity to study the unique biologic participation of the uterus in the
      process of human embryo implantation. AIM: To identify the recipient variables
      that may have a significant impact on pregnancy outcome in order to optimize
      results of an oocyte donation program. DESIGN AND SETTINGS: A prospective study
      conducted from March 1, 2010 to March 31, 2011 at a private tertiary care IVF
      Clinic. Materials and methods A total of 270 recipients resulting in embryo
      transfer as a result of oocyte donation were enrolled. Clinical and Ongoing
      pregnancy rates, Implantation rates were calculated according to different age
      groups, Endometrial thickness, Indication, Day and number of embryos transferred.
      Data was evaluated as chi square analyses with comparative significance
      determined at P <.05. RESULTS: In recipients less than 40 years of age, higher
      ongoing pregnancy and implantation rates (41.9% and 24.6%) were seen as compared
      to recipients above 40 years (21.8% and 13.18%) respectively. Pregnancy and
      implantation rates increased with increasing endometrial thickness but the
      difference was not statistically significant. A higher ongoing pregnancy rate
      (40.9% vs.28.8%) and implantation rate (23% vs.19.6%) was demonstrated with Day 3
      embryo transfer compared to Day 2 transfer. CONCLUSION: A declining endometrial
      receptivity may result in lower implantation and pregnancy rates in recipients
      above the age of 40 years, more pronounced after the age of 45 years. An
      endometrial thickness of >8 mm is considered ideal before transfer. Transfer of
      two selected embryos on day 3 yields a favorable pregnancy outcome with reduced
      multiple pregnancy rates. Recipient's age above 45 years has negative impact on
      pregnancy outcome whereas embryo transfers on Day 3 yields better pregnancy.

PMID- 23531512
TI  - Periprosthetic joint infection: Current concept.
AB  - Periprosthetic joint infection (PJI) is one of the most devastating and costly
      complications following total joint arthroplasty (TJA). Diagnosis and management
      of PJI is challenging for surgeons. There is no "gold standard" for diagnosis of
      PJI, making distinction between septic and aseptic failures difficult.
      Additionally, some of the greatest difficulties and controversies involve
      choosing the optimal method to treat the infected joint. Currently, there is
      significant debate as to the ideal treatment strategy for PJI, and this has led
      to considerable international variation in both surgical and nonsurgical
      management of PJI. In this review, we will discuss diagnosis and management of
      PJI following TJA and highlight some recent advances in this field.

PMID- 23531513
TI  - AICAR inhibits PPARgamma during monocyte differentiation to attenuate
      inflammatory responses to atherogenic lipids.
AB  - AIMS: Transcriptional regulation through peroxisome proliferator-activated
      receptor gamma (PPARgamma) is critical for an altered lipid metabolism during
      monocyte to macrophage differentiation. Here, we investigated how 5
      aminoimidazole-4-carboxamide riboside (AICAR), an activator of AMP-dependent
      protein kinase (AMPK), affects PPARgamma during monocyte differentiation. METHODS
      AND RESULTS: During the differentiation of THP-1 monocytic cells or primary human
      monocytes to macrophages, we observed that AICAR inhibited the expression of
      PPARgamma target genes, such as fatty acid-binding protein 4 or CD36. This effect
      was independent of AICAR conversion to AICAR ribotide and AMPK activation. While
      AICAR increased PPARgamma mRNA expression that paralleled differentiation, it
      inhibited PPARgamma protein synthesis without affecting PPARgamma protein
      stability. Monocytes differentiated to macrophages in the presence of AICAR
      revealed an attenuated uptake of oxidized low-density lipoprotein (oxLDL) and
      reduced oxLDL-triggered c-Jun N-terminal kinase (JNK) activation. JNK and
      endoplasmic reticulum stress responses to the saturated fatty acid palmitate were
      attenuated as well, an effect mimicked by the knockdown of PPARgamma. Although
      PPARgamma has been reported to support alternative macrophage activation, AICAR
      did not inhibit interleukin-4-induced gene expression in differentiating
      monocytes. CONCLUSION: Inhibition of PPARgamma-dependent gene expression during
      monocyte differentiation may contribute to an AICAR-elicited macrophage phenotype
      characterized by reduced inflammatory responses to modified lipoproteins and
      saturated fatty acids.

PMID- 23531514
TI  - Breast cancer drugs dampen vascular functions by interfering with nitric oxide
      signaling in endothelium.
AB  - Widely used chemotherapeutic breast cancer drugs such as Tamoxifen citrate (TC),
      Capecitabine (CP) and Epirubicin (EP) are known to cause various cardiovascular
      side-effects among long term cancer survivors. Vascular modulation warrants
      nitric oxide (NO) signal transduction, which targets the vascular endothelium. We
      hypothesize that TC, CP and EP interference with the nitric oxide downstream
      signaling specifically, could lead to cardiovascular dysfunctions. The results
      demonstrate that while all three drugs attenuate NO and cyclic guanosine mono
      phosphate (cGMP) production in endothelial cells, they caused elevated levels of
      NO in the plasma and RBC. However, PBMC and platelets did not show any
      significant changes under treatment. This implies that the drug effects are
      specific to the endothelium. Altered eNOS and phosphorylated eNOS (Ser-1177)
      localization patterns in endothelial cells were observed following drug
      treatments. Similarly, the expression of phosphorylated eNOS (Ser-1177) protein
      was decreased under the treatment of drugs. Altered actin polymerization was also
      observed following drug treatment, while addition of SpNO and 8Br-cGMP reversed
      this effect. Incubation with the drugs decreased endothelial cell migration
      whereas addition of YC-1, SC and 8Br-cGMP recovered the effect. Additionally
      molecular docking studies showed that all three drugs exhibited a strong binding
      affinity with the catalytic domain of human sGC. In conclusion, results indicate
      that TC, CP and EP cause endothelial dysfunctions via the NO-sGC-cGMP pathway and
      these effects could be recovered using pharmaceutical agonists of NO signaling
      pathway. Further, the study proposes a combination therapy of chemotherapeutic
      drugs and cGMP analogs, which would confer protection against chemotherapy
      mediated vascular dysfunctions in cancer patients.

PMID- 23531515
TI  - Gastaut type idiopathic childhood occipital epilepsy.
AB  - Gastaut type idiopathic childhood occipital epilepsy is an uncommon epileptic
      syndrome characterised by frequent seizures, most commonly presenting as
      elementary visual hallucinations or blindness. Other occipital (non-visual)
      symptoms may also occur. Interictal EEG typically shows occipital paroxysms,
      often with fixation-off sensitivity. Ictal EEG is usually characterised by
      interruption by paroxysms and sudden appearance of low-voltage, occipital, fast
      rhythm and/or spikes. Despite well described clinical and EEG patterns, to our
      knowledge, there are very few reports in the literature with video-EEG recording
      of either seizure semiology or fixation-off phenomena. We present a video-EEG
      recording of a 12-year-old girl with Gastaut type epilepsy, illustrating the
      interictal and ictal aspects of this syndrome. Our aim was to demonstrate the
      clinical and neurophysiological pattern of a typical seizure of Gastaut type
      epilepsy, as well as the fixation-off phenomena, in order to further clarify the
      typical presentation of this syndrome. [Published with video sequences].

PMID- 23531516
TI  - Predicting outcomes using the National Trauma Data Bank: optimum management of
      traumatic blunt carotid and blunt thoracic injury.
AB  - INTRODUCTION: We used the National Trauma Data Bank (NTDB) to examine the
      incidence of blunt thoracic and carotid trauma nationally and survival outcomes
      based on treatment approach. METHODS: All vascular traumas were identified from
      the 2008 NTDB. International Classification of Diseases, 9th Revision (ICD-9)
      diagnosis coding was used to identify 178 blunt thoracic aortic injuries and 313
      traumatic blunt carotid injuries. RESULTS: In all, 2089 vascular traumas were
      identified. Patients with blunt thoracic trauma within the highest injury
      severity score (ISS) range (61-75) had a significant survival advantage when
      observation was compared with endovascular management (P < .05). In the carotid
      trauma cohort, those with the highest ISS range (61-75) had a significant
      survival advantage with open surgery compared with observation (P < .01).
      CONCLUSION: Patients with traumatic blunt thoracic injury and an ISS > 61
      appeared to benefit from endovascular approaches compared with open management.
      Patients with blunt carotid trauma and an ISS > 61 appeared to benefit from open
      surgical management.

PMID- 23531517
TI  - NUP98/JARID1A is a novel recurrent abnormality in pediatric acute
      megakaryoblastic leukemia with a distinct HOX gene expression pattern.
AB  - Cytogenetic abnormalities and early response to treatment are the main prognostic
      factors in acute myeloid leukemia (AML). Recently, NUP98/NSD1 (t(5; 11)(q35;
      p15)), a cytogenetically cryptic fusion, was described as recurrent event in AML,
      characterized by dismal prognosis and HOXA/B gene overexpression. Using split
      signal fluorescence in situ hybridization, other NUP98-rearranged pediatric AML
      cases were identified, including several acute megakaryoblastic leukemia (AMKL)
      cases with a cytogenetically cryptic fusion of NUP98 to JARID1A
      (t(11;15)(p15;q35)). In this study we screened 105 pediatric AMKL cases to
      analyze the frequency of NUP98/JARID1A and other recurrent genetic abnormalities.
      NUP98/JARID1A was identified in 11/105 patients (10.5%). Other abnormalities
      consisted of RBM15/MKL1 (n=16), CBFA2T3/GLIS2 (n=13) and MLL-rearrangements
      (n=13). Comparing NUP98/JARID1A-positive patients with other pediatric AMKL
      patients, no significant differences in sex, age and white blood cell count were
      found. NUP98/JARID1A was not an independent prognostic factor for 5-year overall
      (probability of overall survival (pOS)) or event-free survival (probability of
      event-free survival (pEFS)), although the 5-year pOS for the entire AMKL cohort
      was poor (42 +/- 6%). Cases with RBM15/MLK1 fared significantly better in terms
      of pOS and pEFS, although this was not independent from other risk factors in
      multivariate analysis. NUP98/JARID1A cases were characterized by HOXA/B gene
      overexpression, which is a potential druggable pathway. In conclusion,
      NUP98/JARID1A is a novel recurrent genetic abnormality in pediatric AMKL.

PMID- 23531518
TI  - Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and
      spliceosome component mutations and outcomes.
AB  - We evaluated the prognostic relevance of several clinical and laboratory
      parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia
      (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15
      months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented.
      In univariate analysis, significant risk factors for survival included anemia,
      thrombocytopenia, increased levels of white blood cells, absolute neutrophils,
      absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone
      marrow blasts, and presence of circulating immature myeloid cells (IMCs).
      Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact
      survival. On multivariable analysis, increased AMC (>10 * 10(9)/l, relative risk
      (RR) 2.5, 95% confidence interval (CI) 1.7-3.8), presence of circulating IMC (RR
      2.0, 95% CI 1.4-2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2-2.2) and
      decreased platelet count (<100 * 10(9)/l, RR 1.4, 99% CI 1.0-1.9) remained
      significant. Using these four risk factors, a new prognostic model for overall
      (high risk, RR 4.4, 95% CI 2.9-6.7; intermediate risk, RR 2.0, 95% CI 1.4-2.9)
      and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9-12.8; intermediate
      risk, RR 2.6, 95% CI 1.1-5.9) performed better than other conventional risk
      models and was validated in an independent cohort of 268 CMML patients.

PMID- 23531520
TI  - Health governance by collaboration: a case study on an area-based programme to
      tackle health inequalities in the Dutch city of the Hague.
AB  - BACKGROUND: Area-based programmes are seen as a promising strategy for tackling
      health inequalities. In these programmes, local authorities and other local
      actors collaborate to employ health promoting interventions and policies. Little
      is known about the underlying processes of collaborative governance. To unravel
      this black box, we explored how the authority of The Hague, The Netherlands,
      developed a programme tackling health inequalities drawing on a collaborative
      mode of governance. METHODS: Case study drawing on qualitative semi-structured
      interviews and document review. Data were inductively analysed against the
      concept of collaborative governance. RESULTS: The authority's ambition was to co
      produce a programme on tackling health inequalities with local actors. Three
      stages could be distinguished in the governing process: (i) formulating policy
      objectives, (ii) translating policy objectives into interventions and (iii)
      executing health interventions. In the stage of formulating policy objectives,
      the collaboration led to a reframing of the initial objectives. Furthermore, the
      translation of the policy objectives into health interventions was rather
      pragmatic and loosely based on health needs and/or evidence. As a result, the
      concrete actions that ensued from the programme did not necessarily reflect the
      initial objectives. CONCLUSION: In a local system of health governance by
      collaboration, factors other than the stated policy objectives played a role,
      eventually undermining the effectiveness of the programme in reducing health
      inequalities. To be effective, the processes of collaborative governance
      underlying area-based programmes require the attention of the local authority,
      including the building and governing of networks, a competent public health
      workforce and supportive infrastructures.

PMID- 23531519
TI  - A quantitative trait locus analysis of personality in wild bighorn sheep.
AB  - Personality, the presence of persistent behav105ioral differences among
      individuals over time or contexts, potentially has important ecological and
      evolutionary consequences. However, a lack of knowledge about its genetic
      architecture limits our ability to understand its origin, evolution, and
      maintenance. Here, we report on a genome-wide quantitative trait locus (QTL)
      analysis for two personality traits, docility and boldness, in free-living female
      bighorn sheep from Ram Mountain, Alberta, Canada. Our variance component linkage
      analysis based on 238 microsatellite loci genotyped in 310 pedigreed individuals
      identified suggestive docility and boldness QTL on sheep chromosome 2 and 6,
      respectively. A lack of QTL overlap indicated that genetic covariance between
      traits was not modulated by pleiotropic effects at a major locus and may instead
      result from linkage disequilibrium or pleiotropic effects at QTL of small
      effects. To our knowledge, this study represents the first attempt to dissect the
      genetic architecture of personality in a free-living wildlife population, an
      important step toward understanding the link between molecular genetic variation
      in personality and fitness and the evolutionary processes maintaining this
      variation.

PMID- 23531521
TI  - Examining self-rated health of young central and eastern Europeans in the context
      of other world regions.
AB  - BACKGROUND: Poor health is more prevalent in the east of Europe as compared with
      the west. This variation is often attributed to Soviet communism. Few studies
      investigate this health discrepancy within young adults who were children during
      this period. We studied the health of young adults by examining variations
      between world regions in general health between generations (18-65+). The
      individual and contextual mechanisms that might influence their health were also
      investigated. METHODS: World Health Survey data were analysed on young adults
      aged 18-34 (n = 91,823) and their elders aged 35+ (n = 132 362) from 59
      countries. Main outcome was self-reported general health. Multi-level logistic
      regression was used to assess associations between general health and regions,
      while accounting for individual- and country-level socio-economic factors across
      age ranges. RESULTS: The prevalence of poor health was much higher for young
      adults in the Former Soviet Union region than in Western Europe, with the central
      European region being in-between.This pattern remained even after full
      adjustments, for the Former Soviet Union citizens [odds ratio 4.26 (95%
      confidence interval 1.77-10.24)] and for Central Europeans [odds ratio 1.73 (95%
      confidence interval 0.90-3.32)] as compared with western Europe. Age-specific
      analyses showed East-West health differences usually being larger as age
      increases (up to 65+). This age pattern seemed reversed for the south-west
      divide. CONCLUSIONS: The East-West health gap seems more pronounced for the
      Former Soviet Union young adults, rather than Central Europeans. It appears as
      though young adults from Central Europe might have been somewhat insulated from
      the ill-health effects of communism.

PMID- 23531522
TI  - Parental internalizing problems in a community sample: association with child
      psychosocial problems.
AB  - BACKGROUND: Offspring of depressed, anxious and stressed parents are at increased
      risk of developing mental disorders. However, most studies investigating this
      association concentrate on clinical symptoms. The objective of this study is to
      examine the association between parental internalizing problems (symptoms of
      depression, anxiety and stress) and child psychosocial problems in a community
      sample, crude and adjusted for potential confounders (such as child gender,
      parental educational level, ethnicity) and whether parental concerns affect this
      association. STUDY DESIGN: Preceding a routine health examination, cross
      sectional data were obtained from a representative sample of 9453 parents of
      children aged 9-11 years (response 65%). Measures of parental internalizing
      problems (Depression Anxiety Stress Scale), child psychosocial problems
      (Strengths and Difficulties Questionnaire-Total Difficulties Score), background
      characteristics and parental concerns were completed by the parents. RESULTS:
      Parental internalizing problems were associated with child psychosocial problems
      in crude analysis and after adjustment for child, parent and family
      characteristics [beta = 0.12, 95% confidence interval (CI) = 0.10-0.14]. Parental
      concerns about their child's emotional and behavioural problems were also
      strongly associated with child psychosocial problems. After adjustment for these
      parental concerns, the association of parental stress with child psychosocial
      problems remained, while the association of parental depression and anxiety
      symptoms with child psychosocial problems lost statistical significance.
      CONCLUSIONS: As in clinical samples, parental internalizing problems in a
      community sample are associated with child psychosocial problems. Parental
      concerns on the child seem to affect this association. Further research is needed
      on the mechanisms affecting this association.

PMID- 23531523
TI  - Swine influenza and vaccines: an alternative approach for decision making about
      pandemic prevention.
AB  - BACKGROUND: During the global pandemic of A/H1N1/California/07/2009 (A/H1N1/Cal)
      influenza, many governments signed contracts with vaccine producers for a
      universal influenza immunization program and bought hundreds of millions of
      vaccines doses. We argue that, as Health Ministers assumed the occurrence of the
      worst possible scenario (generalized pandemic influenza) and followed the strong
      version of the Precautionary Principle, they undervalued the possibility of mild
      or weak pandemic wave. METHODOLOGY: An alternative decision rule, based on the
      non-extensive entropy principle, is introduced, and a different Precautionary
      Principle characterization is applied. This approach values extreme negative
      results (catastrophic events) in a different way and predicts more plausible and
      mild events. It introduces less pessimistic forecasts in the case of uncertain
      influenza pandemic outbreaks. A simplified application is presented using
      seasonal data of morbidity and severity among Italian children influenza-like
      illness for the period 2003-10. PRINCIPAL FINDINGS: Established literature
      results predict an average attack rate of not less than 15% for the next pandemic
      influenza [Meltzer M, Cox N, Fukuda K. The economic impact of pandemic influenza
      in the United States: implications for setting priorities for interventions.
      Emerg Infect Dis 1999;5:659-71; Meltzer M, Cox N, Fukuda K. Modeling the Economic
      Impact of Pandemic Influenza in the United States: Implications for Setting
      Priorities for Intervention. Background paper. Atlanta, GA: CDC, 1999. Available
      at: http://www.cdc.gov/ncidod/eid/vol5no5/melt_back.htm (7 January 2011, date
      last accessed))]. The strong version of the Precautionary Principle would suggest
      using this prediction for vaccination campaigns. On the contrary, the non
      extensive maximum entropy principle predicts a lower attack rate, which induces a
      20% saving in public funding for vaccines doses. CONCLUSIONS: The need for an
      effective influenza pandemic prevention program, coupled with an efficient use of
      public funding, calls for a rethinking of the Precautionary Principle. The non
      extensive maximum entropy principle, which incorporates vague and incomplete
      information available to decision makers, produces a more coherent forecast of
      possible influenza pandemic and a conservative spending in public funding.

PMID- 23531524
TI  - Stakeholder perspectives on European priorities for comprehensive liver cancer
      control: a conjoint analysis.
AB  - BACKGROUND: As liver cancer incidence and mortality remain high in many parts of
      Europe, a more comprehensive response is required to reduce the burden. Expert
      stakeholders should be involved in the design of responses because they have
      important insights about potentially effective responses and will be affected by
      policy changes. We aimed to prioritize liver cancer control strategies based on
      European liver cancer stakeholders' views of which strategies would have the
      greatest impact in a comprehensive liver cancer control plan. METHODS: One
      hundred liver cancer clinical, policy and advocacy stakeholders from France,
      Germany, Italy, Spain and Turkey were surveyed. Respondents completed 12 conjoint
      choice tasks in which they chose which of two subsets of 11 strategies would have
      the greatest impact in their country. RESULTS: All strategies were considered
      likely to have a positive impact (P < 0.01). The highest priority strategy was
      monitoring of at-risk populations, followed by centres of excellence, clinical
      education, multidisciplinary management, national guidelines, measuring social
      burden, public awareness, risk assessment and referral, research infrastructure
      and access to treatments. CONCLUSIONS: Canvassing stakeholder views through a
      conjoint analysis survey provided a robust quantitative prioritization that can
      complement traditional qualitative consultation processes. The prioritized
      strategies provide a logical starting point for decision makers considering
      developing national plans or collaborative efforts to achieve comprehensive liver
      cancer control in Europe.

PMID- 23531525
TI  - The role of familial factors in the associations between sickness absence and
      disability pension or mortality.
AB  - BACKGROUND: Little is known about the factors influencing the future situation of
      individuals on sickness absence (SA) or disability pension (DP). The aim was to
      investigate whether being sickness absent is associated with future DP and
      premature death, and whether such associations can be explained by familial
      factors. METHODS: A sample of 45 734 Swedish twins was followed for 13 years. Cox
      proportional hazard models were applied to analyse the associations between
      having a new SA spell/being granted DP in 1995 and DP/mortality during follow-up
      1996-2008. The familial confounding was tested by studying twins that were
      different in their exposure to SA and DP, respectively, during 1995. RESULTS: SA
      strongly predicted DP during a follow-up of 13 years, in both women [hazard
      ratios (HR) 3.03, 95% confidence intervals (CI) 2.82-3.25] and men (HR 3.83, 95%
      CI 3.50-4.18). A minor part of the associations seemed to be explained by
      familial factors. Both SA and DP increased risk for mortality. For SA, HR was
      1.46 (1.27-1.69) for women and 1.31 (1.14-1.51) for men. For DP, HR was 1.38
      (0.92-2.05) for women and 1.73 (1.24-2.42) for men; results suggested a small
      influence of familial factors. CONCLUSION: SA was found to be a long-term risk
      factor for DP and premature death, in both women and men. Familial factors played
      no or a minor role for these associations. Being granted DP in 1995 also
      increased risk for premature death, with a slight indication of familial
      influences in both sexes.

PMID- 23531526
TI  - Vaccine uptake determinants in The Netherlands.
AB  - BACKGROUND: Combining existing data on background characteristics with data from
      immunization registers might give insight into determinants of vaccine uptake,
      which can help to improve communication strategies and invitation policy of
      National Immunisation Programmes. METHODS: The study population consisted of
      children born in 2005 as registered in the Dutch national immunization register
      Praeventis. A hierarchical logistic regression model was used to quantify
      associations between individual vaccination status and proxy variables for ethnic
      background (individual level), socio-economic status (postcode level) and
      religious objection to vaccination (municipal level). RESULTS: Most children
      whose both parents were not born in The Netherlands had a somewhat lower full
      vaccine uptake, for example, children whose both parents were born in Turkey
      [odds ratio = 0.7 (0.6-0.8)] or in Morocco [odds ratio = 0.8 (0.7-0.9)]. The
      partial uptake was also relatively high (3.7-8.0%) compared with children whose
      both parents were born in The Netherlands (3.1%). Municipalities with higher
      religious objection to vaccination and postcode areas with lower socio-economic
      status were also associated with a lower full uptake. CONCLUSIONS: Despite the
      high vaccination coverage in The Netherlands, we were able to identify
      determinants of vaccine uptake by combining existing data sets. This might be an
      example for other countries. The impact of ethnic background and socio-economic
      status is not as well known in The Netherlands as the effect of religious
      objection to vaccination, and deserves more attention. Groups that have a
      relatively high partial uptake deserve special attention because they do not
      reject vaccination in general.

PMID- 23531527
TI  - Urban greenways have the potential to increase physical activity levels cost
      effectively.
AB  - BACKGROUND: For many, physical activity has been engineered out of daily life,
      leading to high levels of sedentariness and obesity. Multi-faceted physical
      activity interventions, combining individual, community and environmental
      approaches, have the greatest potential to improve public health, but few have
      been evaluated. METHODS: Approximately 100,000 people may benefit from improved
      opportunities for physical activity through an urban regeneration project in
      Northern Ireland, the Connswater Community Greenway. Using the macro-simulation
      PREVENT model, we estimated its potential health impacts and cost-effectiveness.
      To do so, we modelled its potential impact on the burden from cardiovascular
      disease, namely, ischaemic heart disease, type 2 diabetes mellitus and stroke,
      and colon and breast cancer, by the year 2050, if feasible increases in physical
      activity were to be achieved. RESULTS: If 10% of those classified as 'inactive'
      (perform less than 150 minutes of moderate activity/week) became 'active', 886
      incident cases (1.2%) and 75 deaths (0.9%) could be prevented with an incremental
      cost-effectiveness ratio of L4469/disability-adjusted life year. For
      effectiveness estimates as low as 2%, the intervention would remain cost
      effective (L18 411/disability-adjusted life year). Small gains in average life
      expectancy and disability-adjusted life expectancy could be achieved, and the
      Greenway population would benefit from 46 less years lived with disability.
      CONCLUSION: The Greenway intervention could be cost-effective at improving
      physical activity levels. Although the direct health gains are predicted to be
      small for any individual, summed over an entire population, they are substantial.
      In addition, the Greenway is likely to have much wider benefits beyond health.

PMID- 23531528
TI  - Application of human mesenchymal and pluripotent stem cell microcarrier cultures
      in cellular therapy: achievements and future direction.
AB  - Mesenchymal stem cells (MSCs) have recently made significant progress with
      multiple clinical trials targeting modulation of immune responses, regeneration
      of bone, cartilage, myocardia, and diseases like Metachromatic leukodystrophy and
      Hurler syndrome. On the other hand, the use of human embryonic and induced
      pluripotent stem cells (hPSCs) in clinical trials is rather limited mainly due to
      safety issues. Only two clinical trials, retinal pigment epithelial
      transplantation and treatment of spinal cord injury were reported. Cell doses per
      treatment can range between 50,000 and 6 billion cells. The current 2-dimensional
      tissue culture platform can be used when low cell doses are needed and it becomes
      impractical when doses above 50 million are needed. This demand for future cell
      therapy has reinvigorated interests in the use of the microcarrier platform for
      generating stem cells in a scalable 3-dimensional manner. Microcarriers developed
      for culturing adherent cell lines in suspension have been used mainly in vaccine
      production and research purposes. Since MSCs grow as monolayers similar to
      conventional adherent cell lines, adapting MSCs to a microcarrier based expansion
      platform has been progressing rapidly. On the other hand, establishing a robust
      microcarrier platform for hPSCs is more challenging as these cells grow in
      multilayer colonies on extracellular matrices and are more susceptible to shear
      stress. This review describes properties of commercially available microcarriers
      developed for cultivation of anchorage dependent cells and present current
      achievements for expansion and differentiation of stem cells. Key issues such as
      microcarrier properties and coatings, cell seeding conditions, medium development
      and improved bioprocess parameters needed for optimal stem cell systems are
      discussed.

PMID- 23531530
TI  - The impact of enriched environment and transplantation of murine cortical
      embryonic stem cells on recovery from controlled cortical contusion injury.
AB  - PURPOSE: The effectiveness of embryonic stem cell (eSC) therapy has been explored
      in many models of neurological disease and several research groups have shown
      that eSC treatment leads to improved outcomes in pre-clinical models of traumatic
      brain injury (TBI). Though functional recovery occurs, few surviving eSCs appear
      to develop neuronal characteristics; instead the majority of the surviving eSC
      express glial phenotypes. Additionally, researchers have shown that enriching the
      post-surgical environment of the subject promotes functional recovery following
      TBI. The purpose of the current project was to determine if post-surgical
      environmental enrichment (EE) impacts the survival, migration, and integration of
      eSCs in a rodent model of TBI and if the presence of these cells lead to improved
      outcomes. METHODS: In the current study, the medial frontal cortex (MFC) of rats
      was injured using a controlled cortical impact (CCI) device. Immediately
      following injury the rats were placed into either EE or standard environment (SE)
      housing and then seven days post-injury rats received either murine cortical eSC
      or media. Behavioral testing consisted of the Morris water maze (MWM), Barnes
      Maze (BM), and Rotarod tasks (RR). RESULTS: On the MWM task, TBI/eSC/EE animals
      performed as well as the Sham/SE and Sham/EE groups. The TBI/eSC/SE,
      TBI/Media/EE, and TBI/Media/SE groups were impaired compared to the controls. By
      the end of training on the BM there were no differences between the Sham,
      TBI/Media/EE, and TBI/eSC/EE groups. On the RR task all animals placed in the EE
      performed equally well and significantly better than their SE housed
      counterparts. By the end of training on the RR task, the TBI/eSC/EE group
      performed as well as the sham counterparts, and though not significant they also
      surpassed the performance of the injured animals that received enrichment or eSC
      treatment alone. CONCLUSIONS: Combing therapeutic strategies with enriching the
      post-injury environment is likely to be an important addition to determining the
      efficacy of pre-clinical therapies.

PMID- 23531529
TI  - Bioreactor engineering of stem cell environments.
AB  - Stem cells hold promise to revolutionize modern medicine by the development of
      new therapies, disease models and drug screening systems. Standard cell culture
      systems have limited biological relevance because they do not recapitulate the
      complex 3-dimensional interactions and biophysical cues that characterize the in
      vivo environment. In this review, we discuss the current advances in engineering
      stem cell environments using novel biomaterials and bioreactor technologies. We
      also reflect on the challenges the field is currently facing with regard to the
      translation of stem cell based therapies into the clinic. 

PMID- 23531531
TI  - Hybridization in natural sympatric populations of Dermacentor ticks in
      northwestern North America.
AB  - Hybridization in ticks has been described in a handful of species and mostly as a
      result of laboratory experiments. We used 148 AFLP loci to describe putative
      hybridization events between D. andersoni and D. variabilis in sympatric
      populations from northwestern North America. Recently, D. variabilis has expanded
      its range westward into the natural range of D. andersoni. Using a sample of 235
      D. andersoni and 62 D. variabilis, we identified 31 individuals as putative
      hybrids: four F2 individuals and 27 backcrosses to D. andersoni (as defined by
      NewHybrids). We found no evidence of hybrids backcrossing into D. variabilis.
      Furthermore, all hybrids presented 16S mtDNA signatures characteristic of D.
      andersoni, which indicates the directionality of the hybrid crosses: female D.
      andersoni * male D. variabilis. We also discovered 13 species-specific AFLP
      fragments for D. andersoni. These loci were found to have a decreased occurrence
      in the putative hybrids and were absent altogether in D. variabilis samples. AFLP
      profiles were also used to determine the levels of genetic population structure
      and gene flow among nine populations of D. andersoni and three of D. variabilis.
      Genetic structure exists in both species (D. andersoni, PhiST = 0.110; D.
      variabilis, PhiST = 0.304) as well as significant estimates of isolation by
      distance (D. andersoni, rho = 0.066, P = 0.001; D. variabilis, rho = 0.729, P =
      0.001).

PMID- 23531532
TI  - Diacylglycerol kinases: regulated controllers of T cell activation, function, and
      development.
AB  - Diacylglycerol kinases (DGKs) are a diverse family of enzymes that catalyze the
      conversion of diacylglycerol (DAG), a crucial second messenger of receptor
      mediated signaling, to phosphatidic acid (PA). Both DAG and PA are bioactive
      molecules that regulate a wide set of intracellular signaling proteins involved
      in innate and adaptive immunity. Clear evidence points to a critical role for
      DGKs in modulating T cell activation, function, and development. More recently,
      studies have elucidated factors that control DGK function, suggesting an added
      complexity to how DGKs act during signaling. This review summarizes the available
      knowledge of the function and regulation of DGK isoforms in signal transduction
      with a particular focus on T lymphocytes.

PMID- 23531533
TI  - Transgenerational, dynamic methylation of stomata genes in response to low
      relative humidity.
AB  - Transgenerational inheritance of abiotic stress-induced epigenetic modifications
      in plants has potential adaptive significance and might condition the offspring
      to improve the response to the same stress, but this is at least partly dependent
      on the potency, penetrance and persistence of the transmitted epigenetic marks.
      We examined transgenerational inheritance of low Relative Humidity-induced DNA
      methylation for two gene loci in the stomatal developmental pathway in
      Arabidopsis thaliana and the abundance of associated short-interfering RNAs
      (siRNAs). Heritability of low humidity-induced methylation was more predictable
      and penetrative at one locus (SPEECHLESS, entropy <= 0.02; chi2 < 0.001) than the
      other (FAMA, entropy <= 0.17; chi2 ns). Methylation at SPEECHLESS correlated
      positively with the continued presence of local siRNAs (r2 = 0.87; p = 0.013)
      which, however, could be disrupted globally in the progeny under repeated stress.
      Transgenerational methylation and a parental low humidity-induced stomatal
      phenotype were heritable, but this was reversed in the progeny under repeated
      treatment in a previously unsuspected manner.

PMID- 23531534
TI  - Aptamers and their potential to selectively target aspects of EGF, Wnt/beta
      catenin and TGFbeta-smad family signaling.
AB  - The smooth identification and low-cost production of highly specific agents that
      interfere with signaling cascades by targeting an active domain in surface
      receptors, cytoplasmic and nuclear effector proteins, remain important challenges
      in biomedical research. We propose that peptide aptamers can provide a very
      useful and new alternative for interfering with protein-protein interactions in
      intracellular signal transduction cascades, including those emanating from
      activated receptors for growth factors. By their targeting of short, linear motif
      type of interactions, peptide aptamers have joined nucleic acid aptamers for use
      in signaling studies because of their ease of production, their stability, their
      high specificity and affinity for individual target proteins, and their use in
      high-throughput screening protocols. Furthermore, they are entering clinical
      trials for treatment of several complex, pathological conditions. Here, we
      present a brief survey of the use of aptamers in signaling pathways, in
      particular of polypeptide growth factors, starting with the published as well as
      potential applications of aptamers targeting Epidermal Growth Factor Receptor
      signaling. We then discuss the opportunities for using aptamers in other complex
      pathways, including Wnt/beta-catenin, and focus on Transforming Growth Factor
      beta/Smad family signaling.

PMID- 23531536
TI  - The protective effects of alpha-lipoic acid on kidneys in type 2 diabetic Goto
      Kakisaki rats via reducing oxidative stress.
AB  - To evaluate the protective effects of alpha-lipoic acid on the kidneys of Goto
      Kakisaki (GK) diabetic rats, ten GK diabetic rats were randomly divided into a
      diabetic control group and a lipoic acid-treated diabetic group with alpha-lipoic
      acid 35 mg.Kg-1 intraperitoneal injections. Four healthy Wistar rats served as
      normal controls. Malonaldehyde (MDA), ascorbic acid (vitamin C), vitamin E,
      glutathione (GSH) and superoxide dismutase (SOD) levels in renal homogenate, and
      urine protein excretion were measured. The expression of mRNA for NF-kappaB,
      NADPH oxidase subunits p22phox and p47phox in renal tissue was examined by
      realtime PCR. Pathological changes in renal tissue were evaluated by light and
      electron microscopy. There were significant increases in urine protein excretion,
      MDA levels and the expression of mRNA of NF-kappaB, p22phox and p47phox, and
      significant decreases in GSH, SOD, vitamin C and vitamin E levels in the diabetic
      control group compared with the normal control group. Pathological changes of
      renal tissue were more progressive in the diabetic control group than in the
      normal control group. All the parameters above were improved in the alpha-lipoic
      acid-treated diabetic group. Oxidative stress is increased in the kidney of type
      2 diabetic GK rats. It is associated with the progression of diabetic
      nephropathy. alpha-lipoic acid can protect renal function in diabetic rats via
      its antioxidant activity.

PMID- 23531535
TI  - Cytokines and the skin barrier.
AB  - The skin is the largest organ of the human body and builds a barrier to protect
      us from the harmful environment and also from unregulated loss of water.
      Keratinocytes form the skin barrier by undergoing a highly complex
      differentiation process that involves changing their morphology and structural
      integrity, a process referred to as cornification. Alterations in the epidermal
      cornification process affect the formation of the skin barrier. Typically, this
      results in a disturbed barrier, which allows the entry of substances into the
      skin that are immunologically reactive. This contributes to and promotes
      inflammatory processes in the skin but also affects other organs. In many common
      skin diseases, including atopic dermatitis and psoriasis, a defect in the
      formation of the skin barrier is observed. In these diseases the cytokine
      composition within the skin is different compared to normal human skin. This is
      the result of resident skin cells that produce cytokines, but also because
      additional immune cells are recruited. Many of the cytokines found in defective
      skin are able to influence various processes of differentiation and
      cornification. Here we summarize the current knowledge on cytokines and their
      functions in healthy skin and their contributions to inflammatory skin diseases.

PMID- 23531537
TI  - Protein contribution to plant salinity response and tolerance acquisition.
AB  - The review is focused on plant proteome response to salinity with respect to
      physiological aspects of plant salt stress response. The attention is paid to
      both osmotic and ionic effects of salinity stress on plants with respect to
      several protein functional groups. Therefore, the role of individual proteins
      involved in signalling, changes in gene expression, protein biosynthesis and
      degradation and the resulting changes in protein relative abundance in proteins
      involved in energy metabolism, redox metabolism, stress- and defence-related
      proteins, osmolyte metabolism, phytohormone, lipid and secondary metabolism,
      mechanical stress-related proteins as well as protein posttranslational
      modifications are discussed. Differences between salt-sensitive (glycophytes) and
      salt-tolerant (halophytes) plants are analysed with respect to differential
      salinity tolerance. In conclusion, contribution of proteomic studies to
      understanding plant salinity tolerance is summarised and discussed.

PMID- 23531538
TI  - Synthesis of 1-isopropyl-3-acyl-5-methyl-benzimidazolone derivatives and their
      antimicrobial activity.
AB  - A series of N-acylated analogues of 1-isopropyl-3-acyl-5-methyl-benzimidazolone
      were synthesized. Bioassay results indicated that analogues 5-07 and 5-19
      exhibited the most potency against Bacillus cereus, Bacillus subtilis,
      Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Analogues 5
      02, 5-07, 5-12, 5-15, 5-19, 5-20 and 5-25 could effectively inhibit the spore
      germination of Botrytis cinerea. The relationship between structure and their
      antimicrobial activity (SAR) has also been discussed according to aliphatic acids
      and aromatic acids derivatives, respectively. This implied that the N-acylated
      derivatives of 5-methyl-benzimidazolone might be potential antimicrobial agents.

PMID- 23531540
TI  - Effects of dietary conjugated linoleic acid and biopolymer encapsulation on lipid
      metabolism in mice.
AB  - Forty mice were randomly divided into four groups on the basis of the diet to be
      fed as follows: 5% (low) fat diet (T1: LF); 20% (high) fat diet (T2: HF); 20% fat
      containing 1% conjugated linoleic acid (CLA) (T3: HFC); and 20% fat containing 1%
      CLA with 0.5% biopolymers (T4: HFCB). The high-fat with CLA diet groups (HFC and
      HFCB) and the low-fat diet group (LF) tended to have lower body weights and total
      adipose tissue weights than those of the high-fat diet group (HF). Serum leptin
      and triglyceride were significantly lower in the high fat with CLA-fed groups
      (HFC and HFCB) and the low-fat diet group (LF) than those in the high-fat diet
      group (HF). It is noteworthy that the high-fat with CLA and biopolymers group
      (HFCB) showed the lowest serum triglyceride and cholesterol concentrations. In
      the high-fat-fed group (HF), voluntary travel distance as a measure of physical
      activity decreased after three weeks of feeding. However, the CLA-fed groups
      showed increased physical activity. The groups fed high-fat diets supplemented
      with CLA alone and with CLA and biopolymers had higher viscosity of small
      intestinal contents than that in the low- and high-fat dietary groups.

PMID- 23531539
TI  - Alternative oxidase: a mitochondrial respiratory pathway to maintain metabolic
      and signaling homeostasis during abiotic and biotic stress in plants.
AB  - Alternative oxidase (AOX) is a non-energy conserving terminal oxidase in the
      plant mitochondrial electron transport chain. While respiratory carbon oxidation
      pathways, electron transport, and ATP turnover are tightly coupled processes, AOX
      provides a means to relax this coupling, thus providing a degree of metabolic
      homeostasis to carbon and energy metabolism. Beside their role in primary
      metabolism, plant mitochondria also act as "signaling organelles", able to
      influence processes such as nuclear gene expression. AOX activity can control the
      level of potential mitochondrial signaling molecules such as superoxide, nitric
      oxide and important redox couples. In this way, AOX also provides a degree of
      signaling homeostasis to the organelle. Evidence suggests that AOX function in
      metabolic and signaling homeostasis is particularly important during stress.
      These include abiotic stresses such as low temperature, drought, and nutrient
      deficiency, as well as biotic stresses such as bacterial infection. This review
      provides an introduction to the genetic and biochemical control of AOX
      respiration, as well as providing generalized examples of how AOX activity can
      provide metabolic and signaling homeostasis. This review also examines abiotic
      and biotic stresses in which AOX respiration has been critically evaluated, and
      considers the overall role of AOX in growth and stress tolerance.

PMID- 23531541
TI  - Impact of notch signaling on inflammatory responses in cardiovascular disorders.
AB  - Notch signaling is a major pathway in cell fate decisions. Since the first
      reports showing the major role of Notch in embryonic development, a considerable
      and still growing literature further highlights its key contributions in various
      pathological processes during adult life. In particular, Notch is now considered
      as a major player in vascular homeostasis through the control of key cellular
      functions. In parallel, confounding evidence emerged that inflammatory responses
      regulate Notch signaling in vitro in endothelial cells, smooth muscle cells or
      vascular infiltrating cells and in vivo in vascular and inflammatory disorders
      and in cardiovascular diseases. This review presents how inflammation influences
      Notch in vascular cells and, reciprocally, emphasizes the functional role of
      Notch on inflammatory processes, notably by regulating key cell functions
      (differentiation, proliferation, apoptosis/survival, activation). Understanding
      how the disparity of Notch receptors and ligands impacts on vasculature biology
      remains critical for the design of relevant and adequate therapeutic strategies
      targeting Notch in this major pathological context.

PMID- 23531542
TI  - Auxin and cytokinin metabolism and root morphological modifications in
      Arabidopsis thaliana seedlings infected with Cucumber mosaic virus (CMV) or
      exposed to cadmium.
AB  - Arabidopsis thaliana L. is a model plant but little information is available
      about morphological root changes as part of a phytohormonal common response
      against both biotic and abiotic stressors. For this purpose, two-week-old
      Arabidopsis seedlings were treated with 10 uM CdSO4 or infected with CMV. After
      12 days the entire aerial parts and the root system were analyzed, and the
      presence of CMV or the accumulation of Cd were detected. Microscopic analysis
      revealed that both CMV and Cd influenced root morphology by a marked development
      in the length of root hairs and an intense root branching if compared to
      controls. Among the three treatments, Cd-treated seedlings showed a shorter root
      axis length and doubled their lateral root diameter, while the lateral roots of
      CMV-infected seedlings were the longest. The root growth patterns were
      accompanied by significant changes in the levels of indole-3-acetic acid, trans
      zeatin riboside, dihydrozeatin riboside, as a probable consequence of the
      regulation of some genes involved in their biosynthesis/degradation. The opposite
      role on root development played by the phythormones studied is discussed in
      detail. The results obtained could provide insights into novel strategies for
      plant defense against pathogens and plant protection against pollutants.

PMID- 23531544
TI  - Primary therapy of Waldenstrom macroglobulinemia with nucleoside analogue-based
      therapy.
AB  - Waldenstrom macroglobulinemia is a rare chronic lymphoproliferative disorder.
      Treatments are currently reserved for symptomatic patients and usually consist of
      nucleoside analogues (NAs), alkylating agents, bortezomib, and monoclonal
      antibodies, alone or in combination. Fludarabine and 2-chlorodeoxyadenosine (2
      CdA) have been studied in first-line treatment of Waldenstrom macroglobulinemia
      (WM) since the end of the 1990s. In monotherapy, response rates vary between 36%
      and 94%. In a phase III trial, fludarabine in monotherapy was more efficient than
      chlorambucil for progression-free survival (PFS) (37.8 vs. 27.1 months), duration
      of response (DOR) (38.5 vs. 21.3 months) and overall survival (OS) (median not
      reached vs. 69.8 months), but the overall response rate (ORR) was similar (45.6%
      and 35.9%). NAs have been studied in combination with rituximab and/or alkylating
      agents for increasing the quality and duration of the response. Hematologic
      toxicities are a major concern, limiting the indication for NAs in first-line
      treatment to patients who are not candidates for autologous stem cell
      transplantation, those in need of rapid control of the disease, or those with
      poor prognostic factors.

PMID- 23531545
TI  - Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs
      and pseudoknot interactions modulating functionality of the viral genome.
AB  - The Dengue virus (DENV) genome contains multiple cis-acting elements required for
      translation and replication. Previous studies indicated that a 719-nt subgenomic
      minigenome (DENV-MINI) is an efficient template for translation and (-) strand
      RNA synthesis in vitro. We performed a detailed structural analysis of DENV-MINI
      RNA, combining chemical acylation techniques, Pb(2+) ion-induced hydrolysis and
      site-directed mutagenesis. Our results highlight protein-independent 5'-3'
      terminal interactions involving hybridization between recognized cis-acting
      motifs. Probing analyses identified tandem dumbbell structures (DBs) within the
      3' terminus spaced by single-stranded regions, internal loops and hairpins with
      embedded GNRA-like motifs. Analysis of conserved motifs and top loops (TLs) of
      these dumbbells, and their proposed interactions with downstream pseudoknot (PK)
      regions, predicted an H-type pseudoknot involving TL1 of the 5' DB and the
      complementary region, PK2. As disrupting the TL1/PK2 interaction, via 'flipping'
      mutations of PK2, previously attenuated DENV replication, this pseudoknot may
      participate in regulation of RNA synthesis. Computer modeling implied that this
      motif might function as autonomous structural/regulatory element. In addition,
      our studies targeting elements of the 3' DB and its complementary region PK1
      indicated that communication between 5'-3' terminal regions strongly depends on
      structure and sequence composition of the 5' cyclization region.

PMID- 23531543
TI  - Toll-like receptors as therapeutic targets for autoimmune connective tissue
      diseases.
AB  - Autoimmune connective tissue diseases (ACTDs) are a family of consistent systemic
      autoimmune inflammatory disorders, including systemic lupus erythematosus (SLE),
      rheumatoid arthritis (RA), systemic sclerosis (SSc) and Sjogren's syndrome (SS).
      IL-1R-like receptors (TLRs) are located on various cellular membranes and sense
      exogenous and endogenous danger-associated molecular patterns (DAMPs) and
      pathogen-associated molecular patterns (PAMPs), playing a critical role in innate
      immune responses. During the past decade, the investigation of TLRs in
      inflammatory autoimmune diseases has been fruitful. In this report, we review the
      significant biochemical, physiological and pathological studies of the key
      functions of TLRs in ACTDs. Several proteins in the TLR signaling pathways (e.g.,
      IKK-2 and MyD88) have been identified as potential therapeutic targets for the
      treatment of ACTDs. Antibodies, oligodeoxyribonucleotides (ODNs) and small
      molecular inhibitors (SMIs) have been tested to modulate TLR signaling. Some drug
      like SMIs of TLR signaling, such as RDP58, ST2825, ML120B and PHA-408, have
      demonstrated remarkable potential, with promising safety and efficacy profiles,
      which should warrant further clinical investigation. Nonetheless, one should bear
      in mind that all TLRs exert both protective and pathogenic functions; the
      function of TLR4 in inflammatory bowel disease represents such an example.
      Therefore, an important aspect of TLR modulator development involves the
      identification of a balance between the suppression of disease-inducing
      inflammation, while retaining the beneficiary host immune response.

PMID- 23531546
TI  - Neisseria conserved hypothetical protein DMP12 is a DNA mimic that binds to
      histone-like HU protein.
AB  - DNA mimic proteins are unique factors that control the DNA-binding activity of
      target proteins by directly occupying their DNA-binding sites. To date, only a
      few DNA mimic proteins have been reported and their functions analyzed. Here, we
      present evidence that the Neisseria conserved hypothetical protein DMP12 should
      be added to this list. Our gel filtration and analytical ultracentrifugation
      results showed that the DMP12 monomer interacts with the dimeric form of the
      bacterial histone-like protein HU. Subsequent structural analysis of DMP12 showed
      that the shape and electrostatic surface of the DMP12 monomer are similar to
      those of the straight portion of the bent HU-bound DNA and complementary to those
      of HU protein dimer. DMP12 also protects HU protein from limited digestion by
      trypsin and enhances the growth rate Escherichia coli. Functionally, HU proteins
      participate in bacterial nucleoid formation, as well as recombination, gene
      regulation and DNA replication. The interaction between DMP12 and HU protein
      might, therefore, play important roles in these DNA-related mechanisms.

PMID- 23531548
TI  - A multimenu system based on the P300 component as a time saving procedure for
      communication with a brain-computer interface.
AB  - The present study investigates a Brain-Computer Interface (BCI) spelling
      procedure based on the P300 evoked potential. It uses a small matrix of words
      arranged in a tree-shaped organization ("multimenu"), and allows the user to
      build phrases one word at a time, instead of letter by letter. Experiments were
      performed in two sessions on a group of seven healthy volunteers. In the former,
      the "multimenu" was tested with a total of 60 choices: 30 "externally-imposed"
      selections and 30 "free-choice" selections. In the latter, 3 * 3 matrices were
      compared with 6 * 6 matrices. Each matrix was composed of letters or words, for a
      total of four matrices. Differences in classifier accuracy, bit rate and
      amplitude of the evoked P300 were evaluated. Average accuracy in all subjects was
      87% with no differences between the selection methods. The 3 * 3 "multimenu"
      obtained the same level of classifier accuracy as the 6 * 6 matrices, even with a
      significantly lower amplitude of the P300. Bit rate was increased when using the
      3 * 3 matrices compared to the 6 * 6 ones. The "multimenu" system was equally
      effective, but faster than conventional, letter-based matrices. By improving the
      speed of communication, this method can be of help to patients with severe
      difficulties in communication.

PMID- 23531547
TI  - The Mediator complex subunit MED25 is targeted by the N-terminal transactivation
      domain of the PEA3 group members.
AB  - PEA3, ERM and ER81 belong to the PEA3 subfamily of Ets transcription factors and
      play important roles in a number of tissue-specific processes. Transcriptional
      activation by PEA3 subfamily factors requires their characteristic amino-terminal
      acidic transactivation domain (TAD). However, the cellular targets of this domain
      remain largely unknown. Using ERM as a prototype, we show that the minimal N
      terminal TAD activates transcription by contacting the activator interacting
      domain (ACID)/Prostate tumor overexpressed protein 1 (PTOV) domain of the
      Mediator complex subunit MED25. We further show that depletion of MED25 disrupts
      the association of ERM with the Mediator in vitro. Small interfering RNA-mediated
      knockdown of MED25 as well as the overexpression of MED25-ACID and MED25-VWA
      domains efficiently inhibit the transcriptional activity of ERM. Moreover,
      mutations of amino acid residues that prevent binding of MED25 to ERM strongly
      reduce transactivation by ERM. Finally we show that siRNA depletion of MED25
      diminishes PEA3-driven expression of MMP-1 and Mediator recruitment. In
      conclusion, this study identifies the PEA3 group members as the first human
      transcriptional factors that interact with the MED25 ACID/PTOV domain and
      establishes MED25 as a crucial transducer of their transactivation potential.

PMID- 23531549
TI  - Short-term effects of proximal femoral derotation osteotomy on kinematics in
      ambulatory patients with spastic diplegia.
AB  - The aim of this retrospective study was to determine the short-term effects of
      proximal femoral derotation osteotomy (FDO) on gait in 53 ambulatory patients
      with spastic diplegia controlling all confounding procedures. All patients showed
      a jump gait pattern and had undergone bilateral rectus femoris transfer, distal
      hamstring lengthening, and tendo-Achilles lengthening as a single-event
      multilevel surgery. Of these, additional bilateral proximal FDOs were included in
      25 patients, defined as the FDO group; the other 28 patients were defined as the
      no-FDO group. Kinematic variables, such as pelvic tilt, minimal hip flexion in
      stance, hip rotation, and foot progression angle, were compared between the two
      groups at postoperative 1 year. Hip extension, hip rotation, and hip adduction
      improved significantly after surgery in the FDO group (P<0.001, P=0.004,
      P=0.028), but not in the no-FDO group. Foot progression angle improved in both
      groups, but the degree of improvement was significantly greater in the FDO group
      (P=0.004). In conclusion, FDO improved hip rotation, hip adduction, and hip
      extension as well as foot progression angle in the ambulatory patients with
      spastic diplegia showing a jump gait.

PMID- 23531550
TI  - Medial column stabilization improves the early result of calcaneal lengthening in
      children with cerebral palsy.
AB  - Calcaneal lengthening is a popular surgical treatment for pronated foot
      deformity. The aim of this study is to assess the effectiveness of medial column
      stabilization in improving the results of calcaneal lengthening for pronated foot
      deformity in ambulatory children with cerebral palsy. Twenty-one consecutive (37
      feet) children with cerebral palsy with pronated foot deformity who received
      calcaneal lengthening from 2004 to 2009 were reviewed. Talonavicular
      stabilizations were performed by either stapling alone or fusion depending on the
      children's age and correctability of midfoot deformity. Satisfaction rates were
      assessed using Mosca's radiographic, Mosca's clinical, and Yoo's clinical
      criteria. Talonavicular coverage angle was also measured. Results between groups
      with and without stabilization of the talonavicular joint were compared. Group 1
      included 11 children (19 feet) who had no talonavicular stabilization. Group 2
      included 10 children (18 feet) who had talonavicular fixation. Groups were
      further divided into subgroups A [Gross Motor Function Classification System
      (GMFCS)<=II] and B (GMFCS>=III). Factors including demography, geographical
      classification, functional status, and preoperative degree of deformity were
      similar between the two groups. After the operation, all four radiographic
      parameters improved significantly. The talonavicular coverage angle was better in
      group 2 than in group 1. Mosca's radiographic results were satisfactory in 73.68%
      of cases in group 1 and 100% in group 2; the difference was statistically
      significant (P=0.027). As for Mosca's clinical results, 63.16% in group 1 and
      83.33% in group 2 achieved satisfactory results (P=0.156). On the basis of Yoo's
      criteria, the results were satisfactory in 57.89% of cases in group 1 and in
      94.44% of cases in group 2 (P=0.012). Further analysis on the satisfaction rates
      between the subgroups showed similar results between the patients in subgroup 1A
      and 2A, and significantly better results in subgroup 2B than in subgroup 1B.
      Concurrent stabilization of the talonavicular joint is an effective method to
      improve clinical and radiographic results of calcaneal lengthening in children
      with cerebral palsy with pronated feet, and the effect is more significant in
      children with worse GMFCS levels.

PMID- 23531551
TI  - A safe bacterial microsyringe for in vivo antigen delivery and immunotherapy.
AB  - The industrial development of active immunotherapy based on live-attenuated
      bacterial vectors has matured. We developed a microsyringe for antigen delivery
      based on the type III secretion system (T3SS) of P. aeruginosa. We applied the
      "killed but metabolically active" (KBMA) attenuation strategy to make this
      bacterial vector suitable for human use. We demonstrate that attenuated P.
      aeruginosa has the potential to deliver antigens to human antigen-presenting
      cells in vitro via T3SS with considerable attenuated cytotoxicity as compared
      with the wild-type vector. In a mouse model of cancer, we demonstrate that this
      KBMA strain, which cannot replicate in its host, efficiently disseminates into
      lymphoid organs and delivers its heterologous antigen. The attenuated strain
      effectively induces a cellular immune response to the cancerous cells while
      lowering the systemic inflammatory response. Hence, a KBMA P. aeruginosa
      microsyringe is an efficient and safe tool for in vivo antigen delivery.

PMID- 23531553
TI  - Corpus callosotomy in a patient with startle epilepsy.
AB  - Startle epilepsy is a syndrome of reflex epilepsy in which the seizures are
      precipitated by a sudden and surprising, usually auditory, stimulus. We describe
      herein a girl who had been suffering with startle-induced seizures since 2 years
      of age. She had focal, tonic and tonic-clonic seizures, refractory to
      antiepileptic treatment. Daily tonic seizures led to very frequent falls and
      morbidity. Neurologically, she had no deficit. Interictal EEG showed slow waves
      and epileptiform discharges in central and fronto-central regions. Video
      polygraphic recordings of seizures, triggered by stimuli, showed generalised
      symmetric tonic posturing with ictal EEG, characterised by an abrupt and diffuse
      electrodecremental pattern of fast activity, followed by alpha-theta rhythm
      superimposed by epileptic discharges predominantly over the vertex and anterior
      regions. Magnetic resonance imaging showed no abnormalities. Corpus callosotomy
      was performed when the patient was 17. Since surgery, the patient (one year
      follow-up) has remained seizure-free. Corpus callosotomy may be considered in
      patients with startle epilepsy and tonic seizures, in the absence of focal
      lesions amenable to surgery. [Published with video sequences].

PMID- 23531552
TI  - Long-term follow-up of foamy viral vector-mediated gene therapy for canine
      leukocyte adhesion deficiency.
AB  - The development of leukemia following gammaretroviral vector-mediated gene
      therapy for X-linked severe combined immunodeficiency disease and chronic
      granulomatous disease (CGD) has emphasized the need for long-term follow-up in
      animals treated with hematopoietic stem cell gene therapy. In this study, we
      report the long-term follow-up (4-7 years) of four dogs with canine leukocyte
      adhesion deficiency (CLAD) treated with foamy viral (FV) vector-mediated gene
      therapy. All four CLAD dogs previously received nonmyeloablative conditioning
      with 200 cGy total body irradiation followed by infusion of autologous, CD34(+)
      hematopoietic stem cells transduced by a FV vector expressing canine CD18 from an
      internal Murine Stem Cell Virus (MSCV) promoter. CD18(+) leukocyte levels were
      >2% following infusion of vector-transduced cells leading to ongoing reversal of
      the CLAD phenotype for >4 years. There was no clinical development of lymphoid or
      myeloid leukemia in any of the four dogs and integration site analysis did not
      reveal insertional oncogenesis. These results showing disease
      correction/amelioration of disease in CLAD without significant adverse events
      provide support for the use of a FV vector to treat children with leukocyte
      adhesion deficiency type 1 (LAD-1) in a human gene therapy clinical trial.

PMID- 23531554
TI  - Effect of oxygen concentration and selected protocol factors on viability and
      gene expression of mouse liver slices.
AB  - Precision cut liver slices (PCLSs) are widely used as a model to study
      hepatotoxicity. For culturing of PCLS diverse protocols are used which could
      affect slices viability and results. We aimed to identify the most optimal
      culture protocol for mouse PCLS. Slices were cultured for 24h under different
      concentrations of serum, glucose, insulin, and oxygen. Thereafter, slices
      viability was assessed by biochemical methods. Transcriptome analysis was
      performed to identify changes introduced by culture at different oxygen
      concentrations (20%, 40%, 60%, and 80% of oxygen). Medium composition did not
      affect the slices viability. Although metabolic competence was unaffected by
      oxygen concentrations, culturing at 80% of oxygen yielded slices with the best
      biochemical characteristics. The comparison of uncultured vs. cultured slices
      revealed 2524 genes to be differentially expressed. Genes involved in drug
      metabolism, peroxisomal and mitochondrial functions were down-regulated while
      several adaptive/stress response processes were up-regulated. Moreover, 80% of
      oxygen was the most favorable condition with respect to maintenance of expression
      of genes involved in drug and energy metabolism. The outcome of this study
      indicates that mouse PCLS are a valuable tool in research on hepatic functions
      and toxicity, particularly if they are cultured under a controlled oxygen
      concentration of 80%.

PMID- 23531555
TI  - The noncellular reduction of MTT tetrazolium salt by TiO2 nanoparticles and its
      implications for cytotoxicity assays.
AB  - We report results of noncellular tests, revealing the occurrence of
      photocatalytic interactions between titanium dioxide (TiO2, titania)
      nanoparticles and the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] cytotoxicity indicator. These interactions induce the reduction of MTT
      and formation of purple formazan under biologically relevant conditions.
      Classical MTT assays have been performed to evaluate the production of formazan
      in DMEM-F12 and RPMI-1640 cell culture media (containing 10% fetal bovine serum
      FBS) treated with Degussa-P25 TiO2 nanoparticles, in the absence of cells. The
      colorimetric determinations revealed the noncellular MTT to formazan
      transformation induced by TiO2 nanoparticles, under conditions commonly used for
      in vitro cytotoxicity testing of nanomaterials. The formazan precipitation was
      found to be proportional to the TiO2 concentration, being enhanced under
      laboratory daylight exposure. The photocatalytic nature of the studied effect was
      assessed under UV irradiation at 365nm. The biological significance of the
      reported reaction was established with respect to cellular reference experiments
      performed on V79-4, HeLa and B16 cell lines. The results show false viability
      increases with up to 14% (for TiO2 concentrations generally higher than
      50MUg/ml), induced by the TiO2-MTT reaction. This type of artifacts may lead to
      underestimated toxicity or false proliferation results.

PMID- 23531556
TI  - Modelling boron-lined proportional counter response to neutrons.
AB  - The detailed Monte Carlo simulation of a boron-lined proportional counter
      response to a neutron source has been presented. The MCNP4C and experimental data
      on different source-moderator geometries have been given for comparison. The
      influence of different irradiation geometries and boron-lining thicknesses on the
      detector response has been studied. 

PMID- 23531557
TI  - Radiation dose reduction to the critical organ with bismuth shielding during
      endovascular coil embolisation for cerebral aneurysms.
AB  - This study evaluated certified dose reduction with bismuth shielding during an
      endovascular coiling procedure for cerebral aneurysms using a thermoluminescent
      dosemeter-100 H. A total of 60 patients were enrolled in the study and randomised
      into two groups (shielding group and unshielded group). In the unshielded group,
      the total dose-area product was 286.46 Gy cm(2), the fluoroscopy time was 61.57
      min and the procedure time was 96.57 min. In the shielding group, those values
      were 256.36 Gy cm(2), 51.10 min and 91.00 min, respectively. The reductions in
      the organ-equivalent doses in the right eye, left eye and thyroid were 32.9 %
      (11.43 mSv), 28.9 % (17.58 mSv) and 68.1 % (20.48 mSv), respectively. The
      reductions in the relative organ doses were 21.6, 20.8, and 64.4 %, respectively.
      Bi shielding was feasible and effective for dose reduction during this
      neurointerventional procedure. 

PMID- 23531558
TI  - Characteristics of airborne radionuclides concentration in a coastal environment.
AB  - Airborne radionuclides from the Fukushima nuclear power plant accident in 2011
      were measured in 12 regional monitoring stations in Korea. The Gangneung (GN)
      monitoring station located in a coastal region almost always has a higher
      radioactivity concentration of airborne radionuclides than any other station. The
      possible cause of this higher concentration was analysed in terms of the local
      meteorology and topography. The increase in surface concentrations of
      radionuclides at the GN region might be attributed to the downslope windstorm,
      temperature inversion and coupled sea breeze and mountain flows. 

PMID- 23531560
TI  - Potential for improved outcomes and quality of life through social justice
      awareness. From the editor.

PMID- 23531559
TI  - Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic
      lateral sclerosis.
AB  - Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower
      cholinergic activity than in healthy individuals in their still preserved spinal
      motoneurons (MNs) suggesting that cholinergic reduction might occur before MN
      death. To unravel how and when cholinergic function is compromised, we have
      analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from
      early presymptomatic stages of the SOD1(G93A) ALS mouse model by confocal
      immunohistochemistry. The analysis showed an early reduction in ChAT content in
      soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic
      interneurons in the lumbar spinal cord of the 30-day-old SOD1(G93A) mice.
      Cholinergic synaptic stripping occurred simultaneously to the presence of
      abundant surrounding major histocompatibility complex II (MHC-II)-positive
      microglia and the accumulation of nuclear Tdp-43 and the appearance of mild
      oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I
      expression, which is necessary for balanced synaptic stripping after axotomy.
      These events occurred before the selective raise of markers of denervation such
      as ATF3. By the same time, alterations in postsynaptic cholinergic-related
      structures were also revealed with a loss of the presence of sigma-1 receptor, a
      Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT
      seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw
      interneurons were drastically diminished. In conclusion, cholinergic dysfunction
      in the local circuitry of the spinal cord may be one of the earliest events in
      ALS etiopathogenesis.

PMID- 23531561
TI  - The influence of computer screen polarity and color on the accuracy of workers'
      reading of graphics.
AB  - BACKGROUND: Many professional workers such as engineers and designers must read
      and comprehend graphics in the workplace. Many studies have analyzed the effects
      of background color when reading text, but few have studied its effects when
      reading graphics. OBJECTIVE: This study examines how different screen polarities
      and background colors can influence the reading and comprehension of graphics.
      PARTICIPANTS: 504 participants were selected by convenience sampling and divided
      into 14 groups. The experiment was performed in three parts. Parts 1 had 2
      groups; Parts 2 had 6 groups; Parts 3 had 6 groups. Each group had 36
      participants. METHODS: In each of the three parts of this study, a combination of
      black and white graphics was used as a background. Three experiments were
      performed. Color was the independent variable; accuracy in reading/comprehending
      graphics was the dependent variable. RESULTS: Experiment One showed that test
      participants performed better in positive (black on white) graphics test than in
      negative (white on black) graphics test on the computer screen. Experiment Two
      showed that screen background colors also significantly affect the accuracy of
      graphics reading/comprehension on the computer screen. Experiment Three showed
      that performance improved when the color of the computer screen polarity was
      adjusted. CONCLUSIONS: Screen polarity can affect the accuracy of graphics
      reading/comprehension; screen background color affects the accuracy of graphics
      reading/comprehension; adequate background color as a contrast increases
      experiments the accuracy of graphics reading/comprehension.

PMID- 23531562
TI  - The meaning and value of traditional occupational practice: a Karen woman's story
      of weaving in the United States.
AB  - This case study sought to understand the meaning of restoring traditional weaving
      as an occupation among Karen women from Burma who now live in an urban city in
      the United States and to examine the impact of weaving on their daily lives in
      terms of identity, empowerment, social support, and opportunities for
      entrepreneurship. The story of one Karen woman, Paw Law Eh, is described. Her
      story exemplifies the negative consequences of restricted access to familiar and
      meaningful daily activities, or "occupations", the relationship between
      occupation and self-identity, how participation in valued occupations can enhance
      social networks, and the restorative effects that are possible when engagement in
      meaningful occupations are maintained or restored. Her story demonstrates that
      occupational therapists have the skills and opportunity to contribute
      significantly to the well-being of Karen women by supporting the restoration of
      the occupation of weaving.

PMID- 23531563
TI  - Untapped resources: refugee employment experiences in central North Carolina.
AB  - OBJECTIVE: The objective of this study was to elucidate a comprehensive
      understanding of the pre-migration expectations and current realities of refugees
      resettled in the United States (U.S). Employment expectations and the current
      work situations experienced by African refugee populations recently resettled in
      Greensboro, NC are examined. PARTICIPANTS: Ten French-speaking refugees of
      African descent who had resided in Central North Carolina for less than three
      years were selected to participate. METHODS: A phenomenological approach was
      used; semi-structured interviews were conducted with participants in spring 2010.
      Interviews needing interpretation were translated throughout the course of the
      interview in real time. All interviews were transcribed verbatim or word for
      word. RESULTS: All participants expected to find work in their fields with
      relative ease, but were either unemployed or under-employed compared to their
      professional training and/or previous occupation in their country of origin at
      the time of their interview. Emergent themes from the interviews included
      financial stability, ease of finding work, identity concerns, English language
      comprehension, the economy, and navigating a new system. CONCLUSIONS: Refugees in
      this sample were not prepared for the challenges they encountered when searching
      for gainful employment. Their experiences appear to be common with available
      anecdotal evidence. Adjustments to the cultural orientation programs received
      prior to migration, and enhancements to social networks in addition to an
      increased focus on English language comprehension post-migration have the
      potential to positively impact employment outcomes for newly arrived refugees.

PMID- 23531564
TI  - Predictors of vocational outcomes using individual placement and support for
      people with mental illness.
AB  - OBJECTIVE: People with disabilities find it harder to enter the labour market
      than people without disabilities and those with a mental illness are, in relation
      to people with other disabilities, employed at an essentially lower extent. Many
      are effectively helped by the vocational rehabilitation model Individual
      Placement and Support (IPS), but there are still many individuals left in
      undesired unemployment. This study investigates potential predictors of the
      vocational outcomes of a one-year follow up of IPS in the north of Sweden.
      PARTICIPANTS: The participants were 65 men and women, mostly younger than 30
      years of age diagnosed with a mental illness (predominantly with a diagnosis of
      anxiety and/or depression). METHODS: Baseline data related to sociodemographic
      and clinical characteristics of the client, the client's own perceptions of every
      day living and participation, self-esteem and quality of life, as well as the
      quantity of employment support, were investigated using analyses of logistic
      regression. RESULTS: Of three identified potential predictors, only psychiatric
      symptoms remained significant in the multivariate logistic regression analyses. A
      lower level of symptoms increased the odds with 5.5 for gaining employment during
      one year. CONCLUSIONS: Careful investigation of how psychiatric symptoms
      influence clients' occupational performance is of importance. By understanding
      essential aspects of the relationships between the clients' individual
      characteristics, the rehabilitation context and the vocational outcomes, more
      appropriate and effective interventions may be offered to the individual client.

PMID- 23531565
TI  - "It's hard to plan your day when you have no money": discouraged workers'
      occupational possibilities and the need to reconceptualize routine.
AB  - OBJECTIVE: This paper presents daily routine as a justice-related concern for
      unemployed people, based on an ethnographic study of discouraged workers.
      PARTICIPANTS: Four women and one man who wanted to work but had ceased searching
      for jobs, and 25 community members whose jobs served the unemployed community,
      participated in the study. METHODS: Ethnographic methodology--including
      participant observation, semi-structured and unstructured interviews, and
      document reviews--and the Occupational Questionnaire were used to gather data for
      10 months in a rural North Carolina town. Data analysis included open and focused
      coding via the Atlas.ti software as well as participant review of findings and
      writings. RESULTS: Routines need to be seen as negotiated, resource-driven
      products of experience rather than automatic structures for daily living.
      Scholars and practitioners must acknowledge that the presence or absence of
      routine not only relates to resource use but also influences unemployed people's
      occupational possibilities. CONCLUSIONS: To address unjust expectations about
      unemployed people's occupational possibilities, scholars must examine the
      uncertain, negotiated nature of daily routine and its function as a foundation
      for occupational engagement. Thus, it may be helpful to view routine as both a
      prerequisite of occupation and a way that existing occupations are organized.

PMID- 23531566
TI  - Wrist and shoulder posture and muscle activity during touch-screen tablet use:
      effects of usage configuration, tablet type, and interacting hand.
AB  - BACKGROUND: Due to its rapid growth in popularity, there is an imminent need for
      ergonomic evaluation of the touch-screen tablet computing form-factor. OBJECTIVE:
      The aim of this study was to assess postures of the shoulders and wrists and
      their associated muscle activity during touch-screen tablet use. METHODS: Fifteen
      experienced adult tablet users completed a set of simulated software tasks on two
      media tablets in a total of seven user configurations. Configurations consisted
      of a combination of a support condition (held with one hand, two hands or in a
      case), a location (on the lap or table surface), and a software task (web
      browsing, email, and game). Shoulder postures were measured by using an infra-red
      LED marker based motion analysis system, wrist postures by electro-goniometry,
      and shoulder (upper trapezius and anterior deltoid) and forearm (flexor carpi
      radialis, flexor carp ulnaris, and extensor radialis) muscle activity by surface
      electromyography. RESULTS: Postures and muscle activity for the wrist
      significantly varied across configurations and between hands, but not across the
      two tablets tested. Wrist extension was high for all configurations and
      particularly for the dominant hand when a tablet was placed on the lap (mean=38
      degrees ). Software tasks involving the virtual keyboard (e-mailing) corresponded
      to higher wrist extensor muscle activity (50th percentile=9.5% MVC) and wrist
      flexion/extension acceleration (mean=322 degrees /s2). High levels of wrist
      radial deviation were observed for the non-dominant hand when it was used to tilt
      and hold the tablet (mean=13 degrees ). Observed differences in posture and
      muscle activity of the shoulder were driven by tablet location. CONCLUSION: Touch
      screen tablet users are exposed to extreme wrist postures that are less neutral
      than other computing technologies and may be at greater risk of developing
      musculoskeletal symptoms. Tablets should be placed in cases or stands that adjust
      the tilt of the screen rather than supporting and tilting the tablet with only
      one hand.

PMID- 23531567
TI  - Symptoms of subordinated importance in fibromyalgia when differentiating working
      from non-working women.
AB  - BACKGROUND: The aim was to identify differences in self-reported symptoms among
      working (W) and non-working (NW) women, and to determine the most important
      biopsychosocial variables in differentiating one group from the other. METHOD: A
      questionnaire was mailed to 524 members of a local chapter of the Swedish
      Rheumatology Association. A total of 362 persons responded (69%); 96% of which
      were women. Women older than 64 years and all men were excluded. The final study
      group consisted of 95 W, and 227 NW women. The questionnaire included data on
      demographics, employment, support, exercise, daily activities and symptoms. Data
      were analysed using univariate statistics and a partial least squares
      discriminant analysis (PLS-DA). RESULTS: The results showed that 41% of the W and
      42% of the NW women were/had been employed in service,care or business. The NW
      women reported a significantly higher severity of symptoms compared with the W
      women. The most important variable when differentiating the W from the NW women
      was social support from colleagues and employers. CONCLUSION: To change
      prevailing attitudes and values towards persons with a work disability, a process
      of active intervention involving staff is needed. Educating employers as to how a
      disability may influence a work situation, and the importance of social support,
      can be improved.

PMID- 23531568
TI  - Associations between leisure activities and binge drinking in adults: findings
      from a Swedish newly sick-listed sample.
AB  - BACKGROUND: Leisure activities and drinking patterns are factors that can affect
      health and ability to return to work after a sick-leave. Associations between
      participation in leisure activities and binge drinking among sick-listed
      individuals have been paid little attention in the research literature.
      OBJECTIVE: The aim of this study was to examine associations between leisure
      activities and binge drinking in a sample of newly sick-listed women and men.
      PARTICIPANTS: The study included 2,888 individuals aged 19-64 years. METHODS:
      Cross-sectional questionnaire data from the Health Assets Project, Sweden, was
      used. Participation in 18 leisure activities was estimated. Binge drinking was
      defined as consuming alcohol at least once a month, and typically consuming five
      or more glasses. RESULTS: Among women aged 19-30 years who regularly went to
      concerts (OR 2.36) and wrote (OR 2.39) associations were found with binge
      drinking. Lower OR was found among women aged 31-64 who regularly went to the
      cinema (OR 0.43), out in the nature (OR 0.46) or participated in sports (OR
      0.57). Among men, associations were found between socializing with friends and
      binge drinking in both age groups (OR 3.83 respectively 1.63). Among younger men
      who attended sporting events OR was 2.31, and among older men participating in
      religious communities OR was 0.28. CONCLUSIONS: This study contributes to
      understanding the interplay between leisure activities and health behavior. In
      particular, social activities in men were associated with binge drinking while
      the opposite was true for recreational activities in older women.

PMID- 23531569
TI  - Determining return to work in a compensation setting: a review of New South Wales
      workplace rehabilitation service provider referrals over 5 years.
AB  - BACKGROUND: Australian workers' compensation data reports a reduction in injury
      rates and claim incidence but no improvement in Return to Work (RTW) rates.
      OBJECTIVE: To identify factors associated with a positive RTW outcome and
      describe those referred to Workplace Rehabilitation Providers (WRPs) in the New
      South Wales (NSW) Australian workers' compensation scheme. METHODS: A
      retrospective review of 65,762 de-identified WRP case records over a 5 year
      period. 9,262 cases specifically referred for RTW assistance were analysed to
      identify factors associated with a positive RTW outcome RESULTS: Overall 47% of
      those referred for RTW services were able to upgrade their work status whilst 30%
      maintained their Stay at Work or pre-referral work status. The significant
      independent predictors associated with a positive RTW outcome were a shorter
      duration of disability (p< 0.001) (0R, 0.971; 95% CI, 0.964-0.977) and a higher
      socio economic index score (p=0.002) (OR, 1.131; 95% CI, 1.045-1.223).
      CONCLUSIONS: The study suggests that WRPs are seeing an increased focus on
      management of workers with increasing disability, with socio-economic
      disadvantage, increasing age, from blue collar backgrounds. The duration of
      disability is a significant determinant in achieving positive RTW outcomes
      suggesting that injured workers should be referred earlier for RTW services.

PMID- 23531570
TI  - Bridging theory and practice: occupational justice and service learning.
AB  - OBJECTIVE: This article presents a service learning pedagogy whereby students
      develop the skills of an evidence-based practice scholar committed to
      occupational justice as a means to transform occupational therapy practice, their
      clients, themselves and the world. PARTICIPANTS: Fifty-four fourth year
      occupational therapy students in a five-year master's program. METHODS: During a
      two-semester course in clinical reasoning, occupational therapy students
      participate in service learning with marginalized and vulnerable populations.
      During the fall semester, students spend time each week observing the population
      and staff, and conducting a needs assessment. At the end of the fall semester,
      students propose a ten-week evidence-based, occupation-focused program. During
      the spring semester, students carry out this project with an occupational justice
      lens. RESULTS: Through qualitative analysis of guided reflections and a final
      service-learning report students identify links between clinical reasoning and
      occupational justice theories and practice in a community context and carryout an
      advocacy plan to promote justice. CONCLUSIONS: Given the opportunity to learn new
      skills in a natural context with a vulnerable population, students demonstrate an
      understanding of occupational injustices and advocate for the rights of those
      they serve, witnessing the resulting changes in policies and practice within the
      community agency and beyond.

PMID- 23531571
TI  - Associations between exposure to information and communication technology (ICT)
      and reported discomfort among adolescents.
AB  - BACKGROUND: Use of Information and Communication Technologies (ICT) are common
      among adolescents in their daily activities.Exposure to ICT has been associated
      with discomfort and musculoskeletal disorders in adults, with growing concern
      about the potential risks to children and adolescents' physical health.
      OBJECTIVE: The objectives of this study were to (i) quantify self-reported
      discomfort and exposure to ICT among adolescents; and (ii) determine if
      associations exist between discomfort and levels of exposure. PARTICIPANTS: The
      participant group comprised 33 Australian adolescents aged 12-15 years. METHODS:
      The study used self-reports by participants for a one week period. Intensity and
      location of discomfort was reported via a written discomfort log. ICT exposure
      and physical activity were reported through an electronic time-use diary.
      RESULTS: The most common ICT types reported by participants were television,
      mobile phones and desktop and laptop computers. Discomfort was reported by 86% of
      participants. The most frequently reported areas were the legs, head/neck, back
      and shoulders. There was no statistical association found between ICT exposure
      and discomfort. The majority of participants exceeded the recommended 60 minutes
      per day of moderate to vigorous physical activity. CONCLUSIONS: High exposure to
      ICT and high prevalence of low level discomfort was reported by the participants.
      Participating in regular physical activity may have some protective effect
      against ICT-related discomfort.

PMID- 23531572
TI  - The predictors of absenteeism due to psychological disability: a longitudinal
      study in the education sector.
AB  - BACKGROUND: Being absent from work because of a psychological disability is
      costly for both individuals and organizations and frequent in employees working
      in the field of education. Absenteeism from work has been mostly studied as an
      organizational withdrawal behavior related to negative factors. OBJECTIVE: The
      purpose of this longitudinal study is to define the predictors of absenteeism due
      to psychological disability by taking into account resources, such as Self
      determined work motivation and Subjective well-being, as well as symptoms of
      Psychological distress. PARTICIPANTS: The sample consisted of 261 employees from
      a Canadian public school organization. METHODS: Independent sample t-tests were
      conducted to compare the mean scores of participants who were not absent from
      work and participants who were absent due to psychological disability. Logistic
      regression analyses were computed for the dependent variable to assess the
      contribution of the three independent variables. RESULTS: Participants who were
      absent from work due to psychological disability in the year following the data
      collection scored significantly lower on resources, and higher on symptoms than
      those participants who were not absent. The three-predictor model was found to be
      significant. However, only Self-determined work motivation and Psychological
      distress significantly predicted absenteeism due to psychological disability.
      CONCLUSIONS: Results are discussed in terms of psychological processes regulating
      the relationships between the work-related factors (i.e., work motivation) and
      life-related factors (i.e., psychological distress and subjective well-being) of
      personal adjustment and accomplishment.

PMID- 23531573
TI  - Beyond a man's world: contributions from considering gender in the study of bus
      drivers' work activity.
AB  - BACKGROUND: Bus driving is a typically male occupation undergoing a process of
      feminization. Although men remain a majority, women's integration has raised some
      questions, namely, related to work organization or its impact on health.
      OBJECTIVE: This paper focuses on the contributions of assuming a gender
      perspective in the analysis of the bus driving occupation and the conditions
      under which it is performed. PARTICIPANTS: Twenty female and 158 male bus
      drivers. METHODS: Qualitative and quantitative approaches were combined.
      Ergonomic work analysis and individual interviews were used, as well as INSAT
      (Work and Health Questionnaire). RESULTS: Difficulties inherent to the work
      activity were highlighted, in terms of working hours and management of
      "peripheral tasks", with implications for the balance between professional and
      personal life. These difficulties were reported differently by men and women,
      although both made themselves clear about the impact on their career and health.
      CONCLUSIONS: Taking gender into consideration has enabled an enrichment of the
      questions that guide the analysis of this work activity, and contributed to a new
      perspective on the work performed by this occupational group as well as a new
      approach to study the history of the transport industry by proposing as focus of
      analysis issues related to "gender mobility".

PMID- 23531574
TI  - Reduction of sickness absence by an occupational health care management program
      focusing on self-efficacy and self-management.
AB  - BACKGROUND: The aim of occupational health care management programs (OHMP) is to
      improve the health status of employees, increase work ability and reduce absence
      time. This includes better coping abilities, work-related self-efficacy and self
      management which are important abilities that should be trained within OHMPs.
      OBJECTIVES: To study the effectiveness of an OHMP including special interventions
      to enhance self-efficacy and self-management. PARTICIPANTS: Employees from the
      German Federal Pension Agency. METHODS: Effects of an OHMP on sickness absence
      was studied by comparing an intervention group and two control groups. A core
      feature of the OHMP were group sessions with all members of working teams,
      focussing on self-efficacy and self management of the individual participant as
      well as the team as a group (focus groups). Participants in the OHMP were asked
      for their subjective evaluation of the focus groups. Rates of sickness absence
      were taken from the routine data of the employer. RESULTS: Participants of the
      OHMP indicated that they had learned better ways of coping and communication and
      that they had generated intentions to make changes in their working situation.
      The rate of sickness absence in the intervention group decreased from 9.26% in
      the year before the OHMP to 7.93% in the year after the program, while there was
      in the same time anincrease of 7.9% and 10.7% in the two control groups.
      CONCLUSIONS: The data suggest that OHMP with focus on self-efficacy and self
      management of individuals and teams are helpful in reducing work absenteeism.

PMID- 23531575
TI  - Schoolbag weight carriage by primary school pupils.
AB  - BACKGROUND: School children usually use a backpack to carry their school
      materials. Carrying heavy schoolbags exceeding the recommended limit may have
      negative health implications. OBJECTIVE: To investigate the weight of schoolbags
      carried by primary school pupils (aged 7-9 years) in Grades 1-3 and determine how
      many pupils carry backpacks in excess of the recommended limit of 10 per cent of
      body weight (%BW). A comparison of the schoolbag weight carried by male and
      female pupils will also be performed. PARTICIPANTS: One hundred and eight healthy
      pupils chosen at random from two participating schools from south-west Poland; 54
      male and 54 female. METHODS: The personal body weight scale was used for
      measuring the weight. The height and weight of each participating pupil was
      measured, and the schoolbag weight of every participant checked over five
      consecutive days, from Monday to Friday. RESULTS: The mean schoolbag weight of
      Grade 1 pupils was 3.23 kg, (i.e.13.1%BW); of Grade 2 pupils, 3.61 kg
      (i.e.12.9%BW) and of Grade 3 pupils 3.37 kg (i.e. 11.1%BW). CONCLUSIONS: 78.3% of
      Grade 1 pupils, 43.3% of Grade 2 pupils and 40.0% of Grade 3 pupils carried
      backpacks exceeding 10%BW. There were no statistically significant differences
      between the mean schoolbag weight of males and females in particular school
      grades.

PMID- 23531576
TI  - Effectiveness of communication strategies for deaf or hard of hearing workers in
      group settings.
AB  - BACKGROUND: In group settings, background noise and an obstructed view of the
      speaker are just a few of the issues that can make workplace communication
      difficult for an individual who is deaf or hard of hearing. Accommodation
      strategies such as amplification of the speaker's voice or the use of text-based
      alternatives exist to address these issues. However, recent studies have shown
      that there are still unmet needs related to workplace communication in group
      settings for individuals who are deaf or hard of hearing. OBJECTIVE: Identify the
      most common strategies used by individuals who are deaf or hard of hearing to
      improve communication in group settings and gauge the perceived effectiveness of
      those strategies. METHOD: An online survey was conducted with individuals who
      self-identified as deaf or hard of hearing. The survey presented specific
      communication strategies based on three functional approaches (aural/oral, text,
      visual). The strategies applied to both receptive and expressive communication in
      five different meeting types ranging in size and purpose. PARTICIPANTS: 161
      adults (age 22-90 yrs.) with limited hearing ability completed the survey.
      RESULTS: Text-based strategies were typically the least frequently used
      strategies in group settings, yet they ranked high in perceived effectiveness for
      receptive and expressive communication. Those who used an interpreter
      demonstrated a strong preference for having a qualified interpreter present in
      the meeting rather than an interpreter acting remotely. For expressive
      communication, participants in general preferred to use their own voice or
      signing abilities and ranked those strategies as highly effective. CONCLUSIONS: A
      more accessible workplace for individuals who are deaf or hard of hearing would
      incorporate more ubiquitous text-based strategy options. Also, qualified
      interpreters, when used, should be present in the meeting for maximum
      effectiveness.

PMID- 23531577
TI  - Workers' strategies to cope with increasing deterioration of working conditions
      in the cleaning sector.
AB  - BACKGROUND: Employees working for office-cleaning companies are directly affected
      by the growing competition in this sector. They face a heavier workload and
      heightened psychological pressure. A majority of these workers are less qualified
      women working part-time, with flexible and inconvenient schedules. OBJECTIVE: The
      objective of the study is to highlight the workers' strategies to deal with fast
      work, schedule requirements and the consequent difficulties to reconcile their
      professional and private life commitments. METHODS: This study is based on in
      depth interviews. PARTICIPANTS: One hundred and twenty-five male and female
      workers responsible for cleaning offices. RESULTS: The themes generated from the
      results highlight a continued deterioration in working conditions in this sector.
      They also show that even approximate respect of the theoretical workload as
      calculated by the sub-contractor and the client company mainly depends on the
      workers' subjective strategies to accommodate increasingly fragmented work hours
      with their private lives. CONCLUSIONS: In conclusion, since these individual
      strategies are not enough to make up for the deterioration in work conditions,
      improving them requires sub-contractors and client companies to agree on
      organisational arrangements that take into account the reality of the employees'
      lives.

PMID- 23531578
TI  - Exploring the impact of resilience, self-efficacy, optimism and organizational
      resources on work engagement.
AB  - BACKGROUND: The German health care system has undergone radical changes in the
      last decades. These days health care professionals have to face economic demands,
      high performance pressure as well as high expectations from patients. To ensure
      high quality medicine and care, highly intrinsic motivated and work engaged
      health care professionals are strongly needed. OBJECTIVE: The aim of this study
      was to examine relations between personal and organizational resources as
      essential predictors for work engagement of German health care professionals.
      METHODS: This investigation has a cross-sectional questionnaire study design.
      Participants were a sample of hospital doctors. Personal strengths, working
      conditions and work engagement were measured by using the SWOPE-K9, COPE Brief
      Questionnaire, Perceived Stress Questionnaire, COPSOQ and Utrecht Work Engagement
      Scale. RESULTS: Significant relations between physicians' personal strengths
      (e.g. resilience, optimism) and work engagement were evaluated. Work related
      factors showed to have a significant influence on work engagement. Differences in
      work engagement were also found with regard to socio-demographic variables.
      CONCLUSION: Results demonstrated important relationships between personal and
      organizational resources and work engagement. Health care management needs to use
      this information to maintain or develop work engaging job conditions in hospitals
      as one key factor to ensure quality health care service.

PMID- 23531579
TI  - Occupational hazards associated with endoscope high-level disinfection: case
      vignettes, review of literature and recommendations for mitigation.
AB  - BACKGROUND: High-level disinfection is crucial in preventing instrument-related
      infections. However, inadequate process and practice may expose technicians to
      chemicals and other hazards. OBJECTIVE: The aim of this article is to describe
      the health effects related to high-level disinfection, the process of identifying
      hazards and safer practice recommendations. PARTICIPANTS: Two endoscope
      technicians with different clinical presentations were evaluated for workplace
      exposures. METHODS: In addition to acute clinical care, corroborative information
      was obtained through walkthrough and observing patients performing their daily
      tasks, interview of co-workers, environmental assessment and review of published
      literature. Recommendations for improvement and clinical follow up were made.
      RESULTS: Clinical evaluation and workplace assessment identified potential
      exposures to: denatonium benzoate, ortho-phthalaldehyde, proteinase subtilisin,
      and isopropyl alcohol. Environmental monitoring showed adequate ventilation but
      with potential for acute high-level exposure to high-level disinfectants.
      Ergonomic stressors and noise were addressed. Following work restrictions and
      work practice changes, both patients were able to return to work without
      recurrence of symptoms. CONCLUSION: The occupational hazards of working in an
      endoscopy disinfection unit include chemicals that are irritants and/or
      allergenic. In addition to bioengineering controls, administrative controls and
      proper respiratory and dermal protections may mitigate exposure and allow workers
      to continue working safely.

PMID- 23531580
TI  - Epilepsy and social security: general aspects of the insured claimants and
      medical decisions.
AB  - BACKGROUND: Epilepsy affects adults at productive age and interferes with their
      ability to work. However, the granting of social security benefits to these
      patients has not received sufficient attention. This article aims to provide a
      profile of individuals with a previous diagnosis of epilepsy that file claims for
      social security benefits and a profile of the medical advisory decisions that
      support the concession of these benefits. PARTICIPANTS: A sample of thirty
      individuals with illness-related problems due to epilepsy was selected from the
      claimants that receive Social Security Incapacity/Sickness benefits. METHODS: An
      exploratory data analysis of the 188 Social Security medical files of the thirty
      claimants was performed using the clinical and epidemiological information and
      the medical advisory criteria. RESULTS: The mean age of the claimants was 39
      years and most of them were males in jobs that do not require a lot of schooling.
      The first claim was filed within an average of four years of employment. On
      average, each worker files a claim every three months, which entitles him/her to
      receive incapacity/sickness benefits for seventeen months. The frequency of
      seizures and the medications used by the claimants were registered in 60% of the
      medical files. In addition, the description of the physical and neurological exam
      was incomplete in 50% of the files. Furthermore, 60% of the files did not include
      the argument or the clinical evidence that was used to justify the concession of
      a benefit. CONCLUSION: The medical advisory decisions on epileptic workers tend
      to be inconsistent, overly lenient and generally lacking in clinical evidence.
      The disparities among the granted benefits indicate the need for the National
      Social Security System to review and draft specific guidelines for epilepsy.

PMID- 23531581
TI  - Work-related psychopathology: rates in different work activities and relationship
      between subjective perception of work distress and psychiatric disturbances.
AB  - BACKGROUND: The link between work distress and negative mental health outcome is
      an emergent topic in the scientific literature. The studies that evaluated the
      risk of work-related psychopathologies in the different job sectors have obtained
      so far controversial and inconclusive results. The identification, by means of
      standardized evaluation tools, of the work activities at higher risk of poor
      mental health is a relevant target for the occupational psychiatry and medicine.
      OBJECTIVE: To evaluate the relationship between the psychosocial work conditions
      and work related psychiatric disturbances and to verify the relationship between
      the higher pathogenic effect of work and specific job activities. PARTICIPANTS: A
      six-month diagnostic trial was conducted on 234 patients (35.4% women and 64.6%
      men). METHODS: Psychiatric diagnoses were according to DSM-IV criteria; anxious
      and depressive dimensions were studied by means of Hamilton-Anxiety-Scale and
      Hamilton Scale for Depression; psychosocial work environments and bio-psycho
      social features were measured by Naples-Questionnaire of Work Distress. Groups
      with higher and lower work-related pathogenesis were compared and their
      distribution among specific job activities was evaluated. RESULTS: Mood disorders
      were strongly linked to negative work environment. Patients with severe bullying
      obtained higher scores on Hamilton-Anxiety-Scale and Hamilton Scale for
      Depression than those with lower work-pathogenesis. The highest scores on Naples
      Questionnaire of Work Distress were related to mood disorders, to poorer bio
      psycho-social functioning and to higher work etiology. No significant
      relationship between work activities and work-related psychopathologies was
      found. CONCLUSION: Workplace bullying is predictive of work-related psychiatric
      disturbances with more severe clinical features and bio-psycho-social
      consequences. No significant differences were found about the relationship
      between work-related psychopathologies and work activities.

PMID- 23531582
TI  - Impact of sound production by wind instruments on the temporomandibular system of
      male instrumentalists.
AB  - BACKGROUND: Playing a wind instrument can be either a reason for overuse or a
      protecting factor against certain diseases. Some individuals have many findings
      but low morbidity while others have few findings but high morbidity. This
      contradictory phenomenon should be researched. OBJECTIVE: The temporomandibular
      system (TMS) is a functional unit which comprises the mandible, associated
      muscles and bilateral joints with the temporal bone. The TMS is responsible for
      the generation of sound when wind instruments are played. Over the long-term and
      with intensive usage, this causes changes in the musculature and in the
      temporomandibular joint (TMJ) of wind musicians, often resulting in
      temporomandibular disorders (TMD). The aim of this study is to examine evidence
      that TMD constitute an occupational disease in wind musicians. PARTICIPANTS: TMD
      patients and wind musicians were examined by dental clinical functional analysis.
      102 male subjects were divided into three groups: "healthy" individuals, wind
      musicians, and patients with TMD. METHODS: Dental Examination was carried out
      based on focused inclusion of the research diagnostic criteria - TMD [1,7].
      Findings were evaluated for statistical significance by first transferring data
      into a digital database [2,15], then generating T-Test und Wilcoxon-Test when non
      Gaussian distribution appears and applying the Mann-Whitney rank sum test using
      Sigmaplot Version 1.1 software (Systat Software Inc, Washington, USA). RESULTS:
      The evaluation revealed that wind instrument musicians show a high incidence of
      developing TMD as the researchers found almost 100% morbidity regarding
      parafunctional habits and preauricular muscle pain of each adult and highly
      active musician. The result is highly significant (p< 0.001) for protrusion
      distance of the mandible. CONCLUSIONS: A higher prevalence of functional
      disorders of the musculoskeletal system has previously been demonstrated in wind
      musicians. New research results and the typical functions of various wind
      instruments provide evidence that playing a wind instrument generates
      occupational risks to the TMS.

PMID- 23531583
TI  - Key personality traits of sales managers.
AB  - BACKGROUND: Sales managers are crucial for producing positive sales outcomes for
      companies. However, there has been a relative dearth of scholarly investigations
      into the personal attributes of sales managers. Such information could prove
      important in the recruitment, selection, training needs identification, career
      planning, counseling, and development of sales managers. OBJECTIVE: Drawing on
      Holland's vocational theory, we sought to identify key personality traits that
      distinguish sales managers from other occupations and are related to their career
      satisfaction. PARTICIPANTS: The main sample was comprised of a total of 978 sales
      managers employed in a large number of companies across the United States (along
      with a comparison sample drawn from 79,512 individuals from other professional
      occupations). METHODS: Participants completed an online version of Resource
      Associates' Personal Style Inventory as well a measure of career satisfaction.
      RESULTS: Our sample of 978 sales managers had higher levels of Assertiveness,
      Customer Service Orientation, Extraversion, Image Management, Optimism, and
      Visionary Style; and lower levels of Conscientiousness, Agreeableness, Intrinsic
      Motivation, Openness, and Tough-Mindedness than a sample of 79,512 individuals in
      a variety of other occupations. Nine of these traits were significantly
      correlated with sales managers' career satisfaction. CONCLUSION: Based on the
      results, a psychological profile of sales managers was presented as were
      implications for their recruitment, selection, training, development, and
      mentoring.

PMID- 23531584
TI  - Musculoskeletal pain and discomfort and associated worker and organizational
      factors: a cross-sectional study.
AB  - BACKGROUND: Musculoskeletal disorders are a leading cause of work-related ill
      health, and a major cost burden for the individual, industry and the community.
      Despite the broad range of risk factors that have been identified, most studies
      have focused only on specific occupations or categories of risk factors, meaning
      that there is limited understanding of the relative contributions of individual
      and organisational, physical and psychosocial factors. OBJECTIVE: This cross
      sectional survey of workers in medium-to-large workplaces in South Australia
      sought to examine a broad range of factors within various workplaces and
      industries. PARTICIPANTS: 404 workers from 29 workgroups and 23 separate
      companies participated in the research. METHODS: Questionnaires were administered
      face-to-face, assessing demographic and job characteristics, safety climate,
      musculoskeletal pain and discomfort (MSPD) and job satisfaction. Potential
      predictors were grouped in terms of personal/job and organizational
      characteristics and associations with MSPD examined. RESULTS: A considerable
      proportion of workers (40%) had experienced MSPD in the last 7 days and 15% had
      experienced severe MSPD. In a multivariate model, four variables were found to be
      significantly associated with MSPD, namely being aged > or =40 years (adjusted
      odds ratio=1.73), overall job satisfaction (negatively associated) (AOR=0.37),
      medium (vs. large) company size (AOR=1.80) and workgroup safety climate score
      (negatively associated) (AOR=0.58). CONCLUSIONS: The results confirm a link
      between non-physical factors and work-related musculoskeletal disorders,
      suggesting that these factors should received increased attention as part of
      overall health and safety strategies. Organizations should give greater
      consideration to both the satisfaction of their employees and organizational
      factors that set the tone for safety climate.

PMID- 23531585
TI  - Important factors influencing the return to work after stroke.
AB  - BACKGROUND: As the field of rehabilitation shifts its focus towards improving
      functional capacity instead of managing disability, return to work (RTW) and
      return to the community emerge as key goals in a person's recovery from major
      disabling illness such as stroke. OBJECTIVE: To compile important factors
      believed to influence RTW after a stroke. METHODS: Based on a comprehensive
      literature review, we clustered similar factors and organized these factors based
      on the International Classification of Function, Disability and Health (ICF)
      framework: body functions or structure, activity participation, environmental
      factors and personal and psychosocial factors. RESULTS: Overall, stroke severity,
      as assessed by the degree of residual disability such as weakness, neurological
      deficit or impairments (speech, cognition, apraxia, agnosia), has been shown to
      be the most consistent negative predictor of RTW. Many factors such as the number
      of working years remaining until retirement, depression, medical history, and
      occupation need to be taken into consideration for stroke survivors, as they can
      influence RTW decision making. Stroke survivors who are flexible and realistic in
      their vocational goal and emotionally accept their disability appear more likely
      to return to work. CONCLUSIONS: There are many barriers to employment for stroke
      survivors ranging from physical and cognitive impairments to psychosocial and
      environmental factors.

PMID- 23531586
TI  - Coping with unemployment: the impact of unemployment on mental health,
      personality, and social interaction skills.
AB  - BACKGROUND: Unemployment is known to be associated with higher levels of
      depressive symptoms. However, there is ambiguity about the direction of this
      association. OBJECTIVE: Different to large surveys, the present pilot-study
      focuses on a detailed characterization of unemployed and strictly matched
      employed subjects. Besides depressive symptoms and personality factors, their
      level of social and communicative skills was determined by an experimental
      behavioral paradigm. PARTICIPANTS: Ninety-two subjects were screened; 62 showed
      relevant exclusion criteria or failed the matching procedure. Finally, 30
      subjects (15 employed, 15 unemployed) participated. METHODS: The experimental
      group-paradigm consisted of a complex standardized challenge situation, which
      demands communicative and social skills for a successful solution. This was
      followed by an individualized video-based behavioral analysis. RESULTS:
      Expectedly, unemployed subjects showed more depressive symptoms than employed
      subjects but did not show higher levels of susceptible personality traits. There
      were no differences between employed and unemployed subjects in social and
      communicative competencies; these skills however correlated positively with the
      level of depression. CONCLUSION: Unemployment is an important stressor, affecting
      mental health. The absence of susceptible traits and skills deficits suggests
      that depressive syndromes are rather resulting than cause of unemployment. Social
      skills do not prevent depressive reactions during unemployment.

PMID- 23531587
TI  - Organization, relational justice and absenteeism.
AB  - BACKGROUND: There is a need for more knowledge on how to manage companies towards
      healthier and more prosperous organizations with low levels of absenteeism.
      Relational Justice can be a useful concept when managing such organizations.
      OBJECTIVE: Organizational factors can help to explain why some companies have
      relatively low absenteeism rates, even though they are equal to other companies
      in many other aspects. Previous studies suggest that management may be one
      important factor. Efficient management may depend on good relations between the
      leaders and the employees. The concept of Relational Justice is designed to
      capture these relations. Consequently, a Relational Justice framework may be used
      to understand why some companies have a low incidence of absenteeism.
      PARTICIPANTS: Managers from a representative body of Swedish companies. METHODS:
      Interviews were analyzed to explore whether the items representing the concept of
      Relational Justice can be used to further understand the strategies, procedures
      and structures that characterize organizations and management in companies with a
      low incidence of absenteeism. RESULTS: Strategies, procedures or principles
      related to Relational Justice were common and highlighted in companies with an
      incidence of absenteeism. The most frequently occurring factors were; to be
      treated with kindness and consideration, personal viewpoint considered and to be
      treated impartially. CONCLUSIONS: The results suggested that a Relational Justice
      framework could be used to increase understanding of the organizational and
      managerial factors typical for companies with a low incidence of absenteeism. A
      Relational Justice approach to organizational management may be used to
      successfully lower absenteeism, change organizations and promote healthy and
      prosperous companies.

PMID- 23531588
TI  - Determinants of on-the-job-barriers in employed persons with multiple sclerosis:
      the role of disability severity and cognitive indices.
AB  - BACKGROUND: Literature has shown that work maintenance is central in order to
      guarantee participation to persons with disability. Knowledge about potential
      sources of difficulties and obstacles is then crucial in order to prevent
      barriers and facilitate work maintenance and career development for persons with
      disabilities. OBJECTIVE: Studies analyzing on-the-job barriers among employed
      people with multiple sclerosis (MS) have found evidence for a role of clinical
      determinants. The aim of this study was to describe in more detail the role of
      disability severity and of cognitive indices on work barriers. PARTICIPANTS:
      Thirty-two employed adults with a diagnosis of MS with mild to moderate
      disability severity were included in the study. They were involved in the
      descriptive study while attending their planned care in the MS unit. METHODS:
      Subjects completed neurocognitive tasks, a self-report measure of executive
      functioning and a face-to-face semi-structured interview exploring their
      perception of barriers at work. RESULTS: Regression analyses showed a specific
      role of disability severity on perception of barriers due to physical, cognitive
      and interpersonal relationships; cognitive indices, on the other hand, predicted
      barriers ascribed to company policy (cognitive score), to accessibility (planning
      score) or difficulties in cognitive and task related abilities (self-rated
      executive functioning). CONCLUSION: These findings underline the relevance of
      objective tasks and self-report questionnaire, direct and indirect multi
      dimensional assessment of functioning for an early intervention planning. An
      ecological model of career development in adults with disabilities is also
      supported.

PMID- 23531589
TI  - Bank robberies: A psychological protocol of intervention in financial
      institutions and principal effects.
AB  - BACKGROUND: Robbery in workplaces represents a potentially traumatic experience
      for workers. OBJECTIVES: This article describes the set up and evaluation of a
      comprehensive psychological intervention designed to help to reduce the adverse
      consequences of bank robberies. PARTICIPANTS: The study population was selected
      among the employees of two Italian banks.METHODS: The psychological protocol was
      designed according to the results of a comprehensive non-systematic review of the
      scientific literature and it was evaluated at work site. RESULTS: The protocol
      consists of a "pre-event" formative intervention and "post-event" psychological
      support. The qualitative data collected allowed us to understand that the
      reactions after a robbery can differ depending on the phase during which the
      workers were exposed to the robbery. We noted that the main consequences can be
      classified in emotional/sentimental reactions, behavioral reactions,
      physiological reactions and experiences during the event; emotions/feelings
      following the robbery and psycho/physical state and emotions/feelings in the
      following days.CONCLUSIONS: In a working environment, the chance to take
      advantage of a specific protocol for the traumatic event of a bank robbery offers
      both the company and the workers important tools for well-being, including post
      robbery psychological support and classroom instructions.

PMID- 23531590
TI  - Modifiable workplace risk factors contributing to workplace absence across health
      conditions: A stakeholder-centered best-evidence synthesis of systematic reviews.
AB  - BACKGROUND: A challenge facing stakeholders is the identification and translation
      of relevant high quality research to inform policy and practice. This study
      engaged academic and community stakeholders in conducting a best evidence
      synthesis to enhance knowledge use. OBJECTIVES: To identify modifiable workplace
      disability risk and protective factors across common health conditions impacting
      work-related absence. METHODS: We searched MEDLINE, Embase, CINHAL, The Cochrane
      Library, PsycINFO, BusinessSourceComplete, and ABI/Inform from 2000 to 2011.
      Systematic reviews that employed quantitative, qualitative, or mixed methods of
      work-focused population were considered for inclusion. Two or more independent
      reviewers reviewed titles only, titles and abstracts, and/or full articles when
      assessing eligibility for inclusion. Selected articles underwent methodological
      screening. RESULTS: The search strategy, expert input and grey literature
      identified 2,467 unique records from which 142 full text articles underwent
      comprehensive review. Twenty-seven systematic reviews met eligibility criteria.
      Modifiable work factors found to have consistent evidence across two or more
      health conditions included lack of social support, increased physical demands at
      work, job strain, lack of supervisory support, increased psychological demands,
      low job satisfaction, low worker control of job, and poor leadership quality.
      CONCLUSIONS: The active engagement of stakeholders led to greater understanding
      of relevance of the study findings for community stakeholders and appreciation of
      the mutual benefits of collaboration.

PMID- 23531591
TI  - Rapid cardiotonic effects of lipid emulsion infusion*.
AB  - OBJECTIVES: Bolus infusion of lipid emulsion can reverse cardiac pharmacotoxicity
      caused by local anesthetics and other lipophilic drugs. The mechanisms of this
      effect are not completely elucidated. The authors test the hypothesis that lipid
      emulsion infusion exerts direct, positive inotropic effects. DESIGN: Prospective,
      randomized animal study. SETTING: University research laboratory. SUBJECTS: Adult
      male Sprague-Dawley rats. INTERVENTIONS: Rats anesthetized with isoflurane were
      given intravenous infusions (9 mL/kg over 1 min) of either 20% soybean oil-based
      emulsion or saline. MEASUREMENTS AND MAIN RESULTS: Arterial pressure and aortic
      flow were measured continuously in intact animals. Lipid infusion increased
      aortic flow and arterial pressure faster and to a greater degree than did the
      same volume of saline infusion. Isolated rat hearts were studied using an
      isovolumetric, constant flow, nonrecirculating system. Left ventricular pressure
      was monitored. The infusion of lipid emulsion in the isolated heart dose
      dependently increased rate pressure product, dP/dt, -dP/dt, and myocardial oxygen
      demand. CONCLUSIONS: Lipid emulsion exerts rapid, positive inotropic and positive
      lusitropic effects in both intact animal and isolated heart models. We
      hypothesize that this inotropy and the resulting increase in tissue blood flow
      contribute to the phenomenon of lipid reversal of cardiac toxicity caused by drug
      overdose.

PMID- 23531592
TI  - Synthesis, characterization and application of a novel starch-based flocculant
      with high flocculation and dewatering properties.
AB  - Flocculation process is one of the most widely used techniques for water and
      wastewater treatment, and also for sludge dewatering. Synthesis of natural
      biopolymers or modification of natural biopolymers as environmentally friendly
      flocculants is highly desired in the field of environmental protection. In this
      work, a water soluble copolymer flocculant, STC-g-PDMC (starch-graft-poly (2
      methacryloyloxyethyl) trimethyl ammonium chloride) was synthesized through
      grafting a monomer, (2-methacryloyloxyethyl) trimethyl ammonium chloride (DMC),
      onto starch initiated by potassium persulphate. Acetone and ethanol were used for
      copolymer precipitation and purification in the synthesis, which diminished the
      toxicity during the synthesis process. The graft copolymer was characterized
      using Fourier-transform infrared spectroscopy, (1)H nuclear magnetic resonance, X
      ray powder diffraction, thermogravimetric analysis and elemental analysis. The
      prepared STC-g-PDMC exhibited a highly effective flocculation capability for
      kaolin suspensions compared with starch and polyacrylamide as control. The charge
      neutralization effect played an important role in the flocculation process at low
      flocculant dosages. When it was used as dewatering agent for anaerobic sludge,
      the conditioned sludge could be easily filtered after the dosage reached 0.696%
      of the dry weight of sludge. Such a graft copolymer is a promising green agent
      for wastewater treatment and sludge dewatering applications.

PMID- 23531593
TI  - Active caspase-3 is removed from cells by release of caspase-3-enriched vesicles.
AB  - Cleavage of Rho associated Coiled Coil kinase I (ROCK I) by caspase-3 contributes
      to membrane blebbing. Whether caspase-3 and ROCK I also play a role in the
      release of membrane vesicles is unknown. Therefore, we transfected a human breast
      cancer cell line (MCF-7) that is caspase-3 deficient, lacks membrane blebbing,
      and does not release membrane vesicles, with caspase-3. Cells expressing caspase
      3 demonstrate both ROCK I-mediated membrane blebbing, and release of small (400
      600nm) membrane vesicles in a ROCK I-independent manner. These membrane vesicles
      contain caspase-3, and are enriched in caspase-3 activity compared to the
      releasing cells. Caspase-3-containing vesicles are taken up by untransfected
      cells but the cells do not show any sign of apoptosis. In conclusion, we show
      that the release of caspase-3-enriched membrane vesicles and membrane blebbing
      are two differentially regulated processes. Furthermore, we hypothesize that
      packaging of caspase-3 into membrane vesicles contributes to cellular homeostasis
      by the removal of caspase-3, and concurrently, protects the cells' environment
      from direct exposure to caspase-3 activity.

PMID- 23531594
TI  - Socioeconomic differences in disability retirement in Finland: the contribution
      of ill-health, health behaviours and working conditions.
AB  - AIMS: Socioeconomic differences in disability retirement are large. In this
      study, the main interest was to find out the contribution of diseases, self-rated
      health, health behaviours and working conditions to socioeconomic differences in
      disability retirement. METHODS: The data are from the nationally-representative
      Health 2000 Survey to which register-based retirement data have been linked.
      These data include 3674 persons aged 30-62 years who were employed at baseline.
      Of the participants, 363 ended up in disability retirement during the follow-up
      period 2000-2009. Cox regression analysis was used to calculate hazard ratios and
      their 95% confidence intervals. RESULTS: The risk of all-cause disability
      retirement was higher among manual workers (HR for men 2.44, 95% CI 1.64-3.63,
      women 2.33, 1.57-3.44) than upper-grade non-manual employees. Ill-health and
      physical working conditions contributed to the socioeconomic differences in
      disability retirement. The importance of physical working conditions was seen in
      particular among those aged 50 years or over and those in disability retirement
      due to musculoskeletal diseases. The contribution of self-rated health was
      stronger in older than younger disability retirees. CONCLUSIONS: Our findings
      suggest that preventing ill-health and improving working conditions, especially
      among the lower socioeconomic classes, would help reduce socioeconomic
      differences in disability retirement.

PMID- 23531595
TI  - Chronic lymphocytic leukemia: a clinical and molecular heterogenous disease.
AB  - The clinical heterogeneity that characterizes chronic lymphocytic leukemia (CLL),
      with survival times ranging from months to decades, reflects its biological
      diversity. Our understanding of the biology of CLL has helped us identify several
      markers of prognostic significance, by which CLL can be differentiated into
      several distinct diseases. The presence of specific chromosomal abnormalities is
      a prognostic indicator of disease progression and survival. Conventional
      cytogenetic analyses have revealed chromosomal aberrations in 40-50% of patients,
      but the detection of abnormalities is limited by the low mitotic activity of CLL
      cells. Metaphase analysis has recently undergone a "revival" because the
      metaphase yield has been improved by stimulation of CLL cells with alternative
      methods. Fluorescence in situ hybridization identifies chromosomal changes in
      approximately 80% of patients with CLL, and comparative genomic hybridization
      using high-density arrays (i.e., array comparative genomic hybridization [aCGH])
      enables high-resolution genome-wide scanning for detecting copy number
      alterations in a single hybridization. The mutational status of the
      immunoglobulin heavy chain variable (IGHV) genes identifies two subsets of CLL
      with different outcomes. Unfortunately, the determination of IGHV mutation status
      may not be practical in all laboratories, and for this reason characteristics
      that are correlated with IGHV mutation status are needed-zeta-chain associated
      (TCR) protein kinase 70 kDa (ZAP-70) being that most commonly used currently in
      routine clinical practice. Whole genome sequencing has offered new insights into
      the mutational status of the disease, highlighting the role of several genes
      previously unrelated to CLL. Of these, NOTCH1 and SF3B1 are the most frequently
      mutated genes that predict poor prognosis. MicroRNA alterations are also involved
      in the initiation and progression of CLL, and the expression levels of some
      microRNAs correlate with previously established prognostic markers such as IGHV
      mutation status or ZAP-70. In addition, both global and gene-specific aberrant
      DNA methylation have been observed in CLL. Aberrant methylation has been
      described for genes that are specifically deregulated in CLL, such as BCL2, TCL1,
      and ZAP-70. Expanding knowledge of aberrant methylation profiles in CLL has a
      potential future impact on diagnosis, prognosis, and prediction of treatment
      response in CLL patients.

PMID- 23531596
TI  - Signal transducer and activator of transcription-3 (Stat3) plays a critical role
      in implantation via progesterone receptor in uterus.
AB  - Recent studies have shown that activation of the signal transducer and activator
      of transcription-3 (Stat3) is required for decidualization, interacting with
      progesterone receptor (PR) in uterus. Based on previous reports, we hypothesized
      that crosstalk between STAT3 and PR signaling is required for successful
      implantation. To identify the interaction between STAT3 and PR isoforms, we
      performed immunoprecipitation following transient cotransfection and found that
      STAT3 physically interacted with PR-A, which is known to be important for uterine
      development and function, but not with PR-B. To further investigate the role of
      Stat3 in uterine function, Stat3 was conditionally ablated only in the PR
      positive cells (PR(cre/+) Stat3(f/f); Stat3(d/d)). Our studies revealed that
      ovarian function and uterine development of Stat3(d/d) mice were normal. However,
      Stat3(d/d) female mice were infertile due to defective embryo implantation.
      Unlike Stat3(f/f) mice, Stat3(d/d) mice exhibited an unclosed uterine lumen.
      Furthermore, uteri of Stat3(d/d) mice were unable to undergo a well-characterized
      hormonally induced decidual reaction. The expression of stromal PR was decreased
      during decidualization and preimplantation period in Stat3(d/d) mice, and PR
      target genes were significantly down-regulated after progesterone induction. Our
      results suggest that STAT3 and PR crosstalk is required for successful
      implantation in the mouse uterus.

PMID- 23531599
TI  - First-principles elucidation of the surface chemistry of the C(2)H(x) (x = 0-6)
      adsorbate series on Fe(100).
AB  - Ab initio total-energy calculations of the elementary reaction steps leading to
      acetylene, ethylene and ethane formation and their decomposition on Fe(100) are
      described. Alongside the endothermicity of all the formation reactions, the
      crucial role played by adsorbed ethyl as main precursor towards both ethylene and
      ethane formation, characterises Fe(100) surface reactivity towards C(2)H(x) (x =
      0-6) hydrocarbon formation in the low coverage limit. A comprehensive scheme
      based on three viable mechanisms towards ethyl formation on Fe(100), including
      methyl/methylene coupling, methyl/methylidyne coupling followed by one
      hydrogenation and methyl/carbon coupling followed by two hydrogenations, is the
      main result of this article.

PMID- 23531598
TI  - Synthesis and anti-influenza virus activities of a novel class of gastrodin
      derivatives.
AB  - A series of substituted aryl glycoside analogues of gastrodin have been
      identified as potential anti-influenza agents. The most potent inhibitor 1a
      exhibited moderate inhibitory activity against the A/Hanfang/359/95(H3N2) and
      A/FM/1/47(H1N1) strains of the influenza A virus (IC(50) values of 44.40 and
      34.45 MUM, respectively) and the oseltamivir-null B/Jifang/13/97 strain of
      influenza B (IC(50) value of 33.01 MUM). In this article, multiple doses of
      compound 1a (80 mg/kg/day, oral administration) were used for the treatment of
      mice infected with influenza A/FM/1/47-MA (H1N1), and surprisingly we found that
      compound 1a significantly increased the number of survivors and prolonged the
      mean survival time. The preliminary studies on the mechanism of antiviral
      activity showed no interaction between compound 1a and the neuraminidase or the
      M2 protein. The novel target to overcome drug resistance combined with its good
      in vivo profile support compound 1a to be a new lead for further development of
      antiviral agents.

PMID- 23531600
TI  - Effects of freshwater clam extract supplementation on time to exhaustion, muscle
      damage, pro/anti-inflammatory cytokines, and liver injury in rats after
      exhaustive exercise.
AB  - The potent anti-inflammatory activities and tissue-protective effects of
      freshwater clams (Corbicula fluminea) have been well reported. The aim of this
      study was to determine the effects of freshwater clam extract (FCE)
      supplementation on time to exhaustion, muscle damage, pro- and anti-inflammatory
      cytokines, and liver injury in rats after exhaustive exercise. Thirty-two rats
      were divided into four groups: sedentary control (SC); SC group with FCE
      supplementation (SC+FCE); exhaustive exercise (E); and E group with FCE
      supplementation (E+FCE). The SC+FCE and E+FCE groups were treated with gavage
      administration of 20 mg/kg for seven consecutive days. Blood samples were
      collected for the evaluation of biochemical parameters. The cytokine levels of
      TNF-alpha and IL-10 were also examined. Twenty-four hours after exhaustive
      exercise, the rat livers were removed for H & E staining. The FCE supplementation
      could extend the time to exhaustion in exercised rats. The levels of CPK, LDH,
      AST, ALT, lactate, TNF-alpha and H & E stains of the liver injury were
      significantly decreased in the E+FCE group, but the blood glucose and IL-10 were
      significantly higher in comparison with the E group. This study suggests that FCE
      supplementation may improve endurance performance and reduce exercise-induced
      muscle damage, inflammatory stress and liver injury.

PMID- 23531597
TI  - Streptococcal collagen-like protein A and general stress protein 24 are
      immunomodulating virulence factors of group A Streptococcus.
AB  - In Western countries, invasive infections caused by M1T1 serotype group A
      Streptococcus (GAS) are epidemiologically linked to mutations in the control of
      virulence regulatory 2-component operon (covRS). In indigenous communities and
      developing countries, severe GAS disease is associated with genetically diverse
      non-M1T1 GAS serotypes. Hypervirulent M1T1 covRS mutant strains arise through
      selection by human polymorphonuclear cells for increased expression of GAS
      virulence factors such as the DNase Sda1, which promotes neutrophil resistance.
      The GAS bacteremia isolate NS88.2 (emm 98.1) is a covS mutant that exhibits a
      hypervirulent phenotype and neutrophil resistance yet lacks the phage-encoded
      Sda1. Here, we have employed a comprehensive systems biology (genomic,
      transcriptomic, and proteomic) approach to identify NS88.2 virulence determinants
      that enhance neutrophil resistance in the non-M1T1 GAS genetic background. Using
      this approach, we have identified streptococcal collagen-like protein A and
      general stress protein 24 proteins as NS88.2 determinants that contribute to
      survival in whole blood and neutrophil resistance in non-M1T1 GAS. This study has
      revealed new factors that contribute to GAS pathogenicity that may play important
      roles in resisting innate immune defenses and the development of human invasive
      infections.

PMID- 23531601
TI  - Sensitivity of scalp 10-20 EEG and magnetoencephalography.
AB  - Although previous studies have investigated the sensitivity of
      electroencephalography (EEG) and magnetoencephalography (MEG) to detect spikes by
      comparing simultaneous recordings, there are no published reports that focus on
      the relationship between spike dipole orientation or sensitivity of scalp EEG/MEG
      and the "gold standard" of intracranial recording (stereotactic EEG). We
      evaluated two patients with focal epilepsy; one with lateral temporal focus and
      the other with insular focus. Two MEG recordings were performed for both
      patients, each recorded simultaneously with initially scalp EEG, based on
      international 10-20 electrode placement with additional electrodes for anterior
      temporal regions, and subsequently stereotactic EEG. Localisation of MEG spike
      dipoles from both studies was concordant and all MEG spikes were detected by
      stereotactic EEG. For the patient with lateral temporal epilepsy, spike
      sensitivity of MEG and scalp EEG (relative to stereotactic EEG) was 55 and 0%,
      respectively. Of note, in this case, MEG spike dipoles were oriented tangentially
      to scalp surface in a tight cluster; the angle of the spike dipole to the
      vertical line was 3.6 degrees. For the patient with insular epilepsy, spike
      sensitivity of MEG and scalp EEG (relative to stereotactic EEG) was 83 and 44%,
      respectively; the angle of the spike dipole to the vertical line was 45.3
      degrees. For the patient with lateral temporal epilepsy, tangential spikes from
      the lateral temporal cortex were difficult to detect based on scalp 10-20 EEG and
      for the patient with insular epilepsy, it was possible to evaluate operculum
      insular sources using MEG. We believe that these findings may be important for
      the interpretation of clinical EEG and MEG.

PMID- 23531603
TI  - Twelve-month outcome following septic arthritis in children.
AB  - There are very few literature data from the last two decades on the rate of
      complications following septic arthritis in children. This retrospective chart
      review shows that 10% of children admitted for septic arthritis to our
      institution suffered from clinically significant complications at 12 months
      following diagnosis. Forty-four children met our inclusion criteria, of whom 59%
      were male and 57% were culture positive. The most common causative organism was
      Staphylococcus aureus (76%), of which only 8% were methicillin-resistant S.
      aureus. Poor prognostic factors were culture positivity, infancy (<2 years) and
      male sex. Our rate of dysfunction is lower than most published rates, which have
      historically been in the range 15 to 49% in developed countries. 

PMID- 23531602
TI  - Voltage Preconditioning Allows Modulated Gene Expression in Neurons Using PEI
      complexed siRNA.
AB  - We present here a high efficiency, high viability siRNA-delivery method using a
      voltage-controlled chemical transfection strategy to achieve modulated delivery
      of polyethylenimine (PEI) complexed with siRNA in an in vitro culture of neuro2A
      cells and neurons. Low voltage pulses were applied to adherent cells before the
      administration of PEI-siRNA complexes. Live assays of neuro2a cells transfected
      with fluorescently tagged siRNA showed an increase in transfection efficiency
      from 62 +/- 14% to 98 +/- 3.8% (after -1 V). In primary hippocampal neurons,
      transfection efficiencies were increased from 30 +/- 18% to 76 +/- 18% (after -1
      V). Negligible or low-level transfection was observed after preconditioning at
      higher voltages, suggesting an inverse relationship with applied voltage.
      Experiments with propidium iodide ruled out the role of electroporation in the
      transfection of siRNAs suggesting an alternate electro-endocytotic mechanism. In
      addition, image analysis of preconditioned and transfected cells demonstrates
      siRNA uptake and loading that is tuned to preconditioning voltage levels. There
      is approximately a fourfold increase in siRNA loading after preconditioning at -1
      V compared with the same at +/-2-3 V. Modulated gene expression is demonstrated
      in a functional knockdown of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in
      neuro2A cells using siRNA. Cell density and dendritic morphological changes are
      also demonstrated in modulated knockdown of brain derived neurotrophic factor
      (BDNF) in primary hippocampal neurons. The method reported here has potential
      applications in the development of high-throughput screening systems for large
      libraries of siRNA molecules involving difficult-to-transfect cells like
      neurons.Molecular Therapy-Nucleic Acids (2013) 2, e82; doi:10.1038/mtna.2013.10;
      published online 26 March 2013.

PMID- 23531604
TI  - Crossing biological barriers for advanced drug delivery.
AB  - This special issue compiles invited and contributed papers of the 9th
      International Conference and Workshop "Biological Barriers", 29 February-9 March
      2012 at Saarland University, Saarbrucken Germany.

PMID- 23531605
TI  - Melanin concentrating hormone induces hippocampal acetylcholine release via the
      medial septum in rats.
AB  - Among various actions of melanin concentrating hormone (MCH), its memory function
      has been focused in animal studies. Although MCH neurons project to various areas
      in the brain, one main target site of MCH is hippocampal formation for memory
      consolidation. Recent immunohistochemical study shows that MCH neurons directly
      project to the hippocampal formation and may indirectly affect the hippocampus
      through the medial septum nucleus (MS). It has been reported that sleep is
      necessary for memory and that hippocampal acetylcholine (ACh) release is
      indispensable for memory consolidation. However, there is no report how MCH
      actually influences the hippocampal ACh effluxes in accordance with the sleep
      wake cycle changes. Thus, we investigated the modulatory function of
      intracerebroventricular (icv) injection of MCH on the sleep-wake cycle and ACh
      release using microdialysis techniques. Icv injection of MCH significantly
      increased the rapid eye movement (REM) and non-REM episode time and the
      hippocampal, not cortical, ACh effluxes. There was a significant correlation
      between REM episode time and hippocampal ACh effluxes, but not between REM
      episode time and cortical ACh effluxes. Microinjection of MCH into the MS
      increased the hippocampal ACh effluxes with no influence on the REM episode time.
      It appears that the effect sites of icv MCH for prolongation of REM episode time
      may be other neuronal areas than the cholinergic neurons in the MS. We conclude
      that MCH actually increases the hippocampal ACh release at least in part through
      the MS in rats.

PMID- 23531606
TI  - LCA and emergy accounting of aquaculture systems: towards ecological
      intensification.
AB  - An integrated approach is required to optimise fish farming systems by maximising
      output while minimising their negative environmental impacts. We developed a
      holistic approach to assess the environmental performances by combining two
      methods based on energetic and physical flow analysis. Life Cycle Assessment
      (LCA) is a normalised method that estimates resource use and potential impacts
      throughout a product's life cycle. Emergy Accounting (EA) refers the amount of
      energy directly or indirectly required by a product or a service. The combination
      of these two methods was used to evaluate the environmental impacts of three
      contrasting fish-farming systems: a farm producing salmon in a recirculating
      system (RSF), a semi-extensive polyculture pond (PF1) and an extensive
      polyculture pond (PF2). The RSF system, with a low feed-conversion ratio (FCR =
      0.95), had lower environmental impacts per tonne of live fish produced than did
      the two pond farms, when the effects on climate change, acidification, total
      cumulative energy demand, land competition and water dependence were considered.
      However, RSF was clearly disconnected from the surrounding environment and
      depended highly on external resources (e.g. nutrients, energy). Ponds adequately
      incorporated renewable natural resources but had higher environmental impacts due
      to incomplete use of external inputs. This study highlighted key factors
      necessary for the successful ecological intensification of fish farming, i.e.,
      minimise external inputs, lower the FCR, and increase the use of renewable
      resources from the surrounding environment. The combination of LCA and EA seems
      to be a practical approach to address the complexity of optimising biophysical
      efficiency in aquaculture systems.

PMID- 23531607
TI  - Dosimetric comparison of intensity modulated radiotherapy isocentric field plans
      and field in field (FIF) forward plans in the treatment of breast cancer.
AB  - The present study is aimed at comparing the planning and delivery efficiency
      between three-dimensional conformal radiotherapy (3D-CRT), field-in-field,
      forward planned, intensity modulated radiotherapy (FIF-FP-IMRT), and inverse
      planned intensity modulated radiotherapy (IP-IMRT). Treatment plans of 20
      patients with left-sided breast cancer, 10 post-mastectomy treated to a
      prescribed dose of 45 Gy to the chest wall in 20 fractions, and 10 post-breast
      conserving surgery to a prescribed dose of 50 Gy to the whole breast in 25
      fractions, with 3D-CRT were selected. The FiF-FP-IMRT plans were created by
      combining two open fields with three to four segments in two tangential beam
      directions. Eight different beam directions were chosen to create IP-IMRT plans
      and were inversely optimized. The homogeneity of dose to planning target volume
      (PTV) and the dose delivered to heart and contralateral breast were compared
      among the techniques in all the 20 patients. All the three radiotherapy
      techniques achieved comparable radiation dose delivery to PTV-95% of the
      prescribed dose covering > 95% of the breast PTV. The mean volume of PTV
      receiving 105% (V105) of the prescribed dose was 1.7% (range 0-6.8%) for IP-IMRT,
      1.9% for FP-IMRT, and 3.7% for 3D-CRT. The homogeneity and conformity indices (HI
      and CI) were similar for 3D-CRT and FP-IMRT, whereas the IP-IMRT plans had better
      conformity index at the cost of less homogeneity. The 3D-CRT and FiF-FP-IMRT
      plans achieved similar sparing of critical organs. The low-dose volumes (V5Gy) in
      the heart and lungs were larger in IP-IMRT than in the other techniques. The
      value of the mean dose to the ipsilateral lung was higher for IP-IMRT than the
      values for with FiF-FP-IMRT and 3D-CRT. In the current study, the relative volume
      of contralateral breast receiving low doses (0.01, 0.6, 1, and 2Gy) was
      significantly lower for the FiF-FP-IMRT and 3D-CRT plans than for the IP-IMRT
      plan. Compared with 3D-CRT and IP-IMRT, FiF-FP-IMRT proved to be a simple and
      efficient planning technique for breast irradiation. It provided dosimetric
      advantages, significantly reducing the size of the hot spot and minimally
      improving the coverage of the target volume. In addition, it was felt that FiF-FP
      IMRT required less planning time and easy field placements.

PMID- 23531608
TI  - Clinico-pathological investigations of Rasmussen encephalitis suggest multifocal
      disease progression and associated focal cortical dysplasia.
AB  - Rasmussen encephalitis is a devastating neurological disorder characterised by
      seizures, brain inflammation, and progressive hemispheric atrophy. The objective
      of the current study was to systematically characterise patterns of structural
      lesions in children with Rasmussen encephalitis, referred for modified anatomical
      hemispherectomy at the Tsinghua University Epilepsy Center in Beijing. Seven
      consecutive patients were investigated with a mean age at operation of 4.5 years,
      who suffered from medically intractable seizures for a mean of 1.6 years. Foci of
      abnormally increased T2 signal intensity were observed in all patients. With the
      exception of one child, all patients presented with progressive unilateral
      cerebral atrophy. FDG-PET imaging revealed extensive regions of hypometabolism
      within the affected cerebral hemisphere in 3 of 4 patients. Diagnosis of
      Rasmussen encephalitis was confirmed histologically, demonstrating CD68 positive
      microglial nodules, as well as CD3 and CD8 positive T lymphocytes invading the
      cerebral parenchyma. An intriguing observation was the heterogenous distribution
      of patterns of lesions throughout the affected hemisphere, suggesting multifocal
      manifestation and distinct sequences of disease progression, from discrete foci
      of inflammatory infiltrates (stage 1) to extensive cortical destruction (stage
      4). Atypical hippocampal sclerosis (HS), with neuronal cell loss affecting most
      prominently the CA4 region (HS type 3 or end folium sclerosis), was evident in 5
      of 7 cases. Four hippocampi also showed chronic inflammation. In addition, we
      observed associated focal cortical dysplasia (FCD; ILAE type IIId) in 4 of 7
      children, supporting the concept of acquired and postmigratory FCD
      pathomechanisms. Postsurgical seizure freedom was achieved in all children with a
      mean follow-up period of 2.7 years and continuous antiepileptic medication.

PMID- 23531611
TI  - Forecasting the Revenues of Local Public Health Departments in the Shadows of the
      "Great Recession".
AB  - CONTEXT: The ability of local health departments (LHD) to provide core public
      health services depends on a reliable stream of revenue from federal, state, and
      local governments. This study investigates the impact of the "Great Recession" on
      major sources of LHD revenues and develops a fiscal forecasting model to predict
      revenues to LHDs in one state over the period 2012 to 2014. Economic forecasting
      offers a new financial planning tool for LHD administrators and local government
      policy makers. This study represents a novel research application for these
      econometric methods. METHODS: Detailed data on revenues by source for each LHD in
      Wisconsin were taken from annual surveys conducted by the Wisconsin Department of
      Health Services over an 8-year period (2002-2009). A forecasting strategy
      appropriate for each revenue source was developed resulting in "base case"
      estimates. An analysis of the sensitivity of these revenue forecasts to a set of
      alternative fiscal policies by the federal, state, and local governments was
      carried out. FINDINGS: The model forecasts total LHD revenues in 2012 of $170.5
      million (in 2010 dollars). By 2014, inflation-adjusted revenues will decline by
      $8 million, a reduction of 4.7%. Because of population growth, per capita real
      revenues of LHDs are forecast to decline by 6.6% between 2012 and 2014. There is
      a great deal of uncertainty about the future of federal funding in support of
      local public health. A doubling of the reductions in federal grants scheduled
      under current law would result in an additional $4.4 million decline in LHD
      revenues in 2014. CONCLUSIONS: The impact of the Great Recession continues to
      haunt LHDs. Multiyear revenue forecasting offers a new financial tool to help
      LHDs better plan for an environment of declining resources. New revenue sources
      are needed if sharp drops in public health service delivery are to be avoided.

PMID- 23531612
TI  - Postnatal development of the endocrine pancreas in mice lacking functional GABAB
      receptors.
AB  - Adult mice lacking functional GABAB receptors (GABAB1KO) have glucose metabolism
      alterations. Since GABAB receptors (GABABRs) are expressed in progenitor cells,
      we evaluated islet development in GABAB1KO mice. Postnatal day 4 (PND4) and
      adult, male and female, GABAB1KO, and wild-type littermates (WT) were weighed and
      euthanized, and serum insulin and glucagon was measured. Pancreatic glucagon and
      insulin content were assessed, and pancreas insulin, glucagon, PCNA, and GAD65/67
      were determined by immunohistochemistry. RNA from PND4 pancreata and adult
      isolated islets was obtained, and Ins1, Ins2, Gcg, Sst, Ppy, Nes, Pdx1, and Gad1
      transcription levels were determined by quantitative PCR. The main results were
      as follows: 1) insulin content was increased in PND4 GABAB1KO females and in both
      sexes in adult GABAB1KOs; 2) GABAB1KO females had more clusters (<500 MUm(2)) and
      less islets than WT females; 3) cluster proliferation was decreased at PND4 and
      increased in adult GABAB1KO mice; 4) increased beta-area at the expense of the
      alpha-cell area was present in GABAB1KO islets; 5) Ins2, Sst, and Ppy
      transcription were decreased in PND4 GABAB1KO pancreata, adult GABAB1KO female
      islets showed increased Ins1, Ins2, and Sst expression, Pdx1 was increased in
      male and female GABAB1KO islets; and 6) GAD65/67 was increased in adult GABAB1KO
      pancreata. We demonstrate that several islet parameters are altered in GABAB1KO
      mice, further pinpointing the importance of GABABRs in islet physiology. Some
      changes persist from neonatal ages to adulthood (e.g., insulin content in
      GABAB1KO females), whereas other features are differentially regulated according
      to age (e.g., Ins2 was reduced in PND4, whereas it was upregulated in adult
      GABAB1KO females).

PMID- 23531614
TI  - High-fat diet-induced hyperinsulinemia and tissue-specific insulin resistance in
      Cry-deficient mice.
AB  - Perturbation of circadian rhythmicity in mammals, either by environmental
      influences such as shiftwork or by genetic manipulation, has been associated with
      metabolic disturbance and the development of obesity and diabetes. Circadian
      clocks are based on transcriptional/translational feedback loops, comprising
      positive and negative components. Whereas the metabolic effects of deletion of
      the positive arm of the clock gene machinery, as in Clock- or Bmal1-deficient
      mice, have been well characterized, inactivation of Period genes (Per1-3) as
      components of the negative arm have more complex, sometimes contradictory effects
      on energy homeostasis. The CRYPTOCHROMEs are critical interaction partners of
      PERs, and simultaneous deletion of Cry1 and -2 results in behavioral and
      molecular circadian arrhythmicity. We show that, when challenged with a high-fat
      diet, Cry1/2(-/-) mice rapidly gain weight and surpass that of wild-type mice,
      despite displaying hypophagia. Transcript analysis of white adipose tissue
      reveals upregulated expression of lipogenic genes, many of which are insulin
      targets. High-fat diet-induced hyperinsulinemia, as a result of potentiated
      insulin secretion, coupled with selective insulin sensitivity in adipose tissue
      of Cry1/2(-/-) mice, correlates with increased lipid uptake. Collectively, these
      data indicate that Cry deficiency results in an increased vulnerability to high
      fat diet-induced obesity that might be mediated by increased insulin secretion
      and lipid storage in adipose tissues.

PMID- 23531613
TI  - Muscle mTORC1 suppression by IL-6 during cancer cachexia: a role for AMPK.
AB  - Although catabolic signaling has a well-established role in muscle wasting during
      cancer cachexia, the suppression of anabolic signaling also warrants further
      investigation. In cachectic tumor-bearing mice, circulating IL-6 levels are
      associated with suppressed muscle protein synthesis and mTORC1 signaling. We have
      found AMPK and IGF-I/insulin signaling, two well-known regulators of the
      mammalian target of rapamycin (mTOR), are altered with the progression of
      cachexia. How IL-6 can induce suppression of mTORC1 signaling remains to be
      established. The purpose of this study was to examine mTOR complex 1 (mTORC1)
      activation and regulation by IL-6 during cancer cachexia. IL-6 effects on mTOR
      activation were examined in Apc(Min/+) mouse skeletal muscle and C2C12 myotubes.
      Systemic IL-6 overexpression in Apc(Min/+) mice produced a dose-dependent
      suppression of mTOR signaling that corresponded to induction of STAT3 and AMPK
      phosphorylation. This result was also evident in IL-6-treated myotubes. Basal
      mTOR activation and mTOR responsiveness to glucose administration were suppressed
      in cachectic skeletal muscle. However, insulin induction of mTOR activity was
      maintained in IL-6-treated myotubes. Whereas IL-6 suppression of myotube mTOR
      activity was rescued by AMPK inhibition, inhibition of STAT3 signaling was not
      sufficient to rescue IL-6 suppression of mTOR activity. Last, treadmill exercise
      training was able to prevent IL-6-induced inhibition of mTOR signaling in
      Apc(Min/+) mice independently of activated STAT. In conclusion, we report dose
      dependent suppression of mTOR activity by IL-6 and suppressed mTOR responsiveness
      to glucose administration in Apc(Min/+) mice. IL-6 suppression of mTOR activity
      was dependent on AMPK activation and independent of STAT signaling in myotubes.

PMID- 23531615
TI  - Effects of prolonged exendin-4 administration on hypothalamic-pituitary-adrenal
      axis activity and water balance.
AB  - Exendin-4 (Ex-4) is a natural agonist of the glucagon-like peptide-1 (GLP-1)
      receptor, currently being used as a treatment for type 2 diabetes mellitus due to
      its insulinotropic properties. Previous studies have revealed that acute
      administration of both GLP-1 and, in particular, Ex-4 potently stimulates
      hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, the effects of
      prolonged Ex-4 exposure on HPA function were explored. To this end, Sprague
      Dawley rats were subjected to a daily regimen of two Ex-4 injections (5 MUg/kg
      sc) for a minimum of 7 days. We found that subchronic Ex-4 administration
      produced a number of effects that resemble chronic stress situations, including
      hyperactivation of the HPA axis during the trough hours, disruption of
      glucocorticoid circadian secretion, hypertrophy of the adrenal gland, decreased
      adrenal gland sensitivity, impaired pituitary-adrenal stress responses, and
      reductions in both food intake and body weight. In addition, a threefold increase
      in diuresis was observed followed by a 1.5-fold increase in water intake; these
      latter effects were abolished by adrenalectomy. Together, these findings indicate
      that Ex-4 induces a profound dysregulation of HPA axis activity that may also
      affect renal function.

PMID- 23531616
TI  - Calcium-sensing receptor-dependent activation of CREB phosphorylation in HEK293
      cells and human parathyroid cells.
AB  - In addition to its acute effects on hormone secretion, epithelial transport, and
      shape change, the calcium-sensing receptor (CaSR) modulates the expression of
      genes that control cell survival, proliferation, and differentiation as well as
      the synthesis of peptide hormones and enzymes. In the present study, we
      investigated the impacts of a CaSR agonist and several CaSR modulators on
      phosphorylation of transcription factor CREB residue Ser(133) in CaSR-expressing
      HEK293 (HEK-CaSR) cells and human adenomatous parathyroid cells. Elevated Ca(2+)o
      concentration had no effect on CREB phosphorylation (p-CREB) in control HEK293
      cells but stimulated p-CREB in both HEK-CaSR cells and human parathyroid cells.
      In addition, p-CREB was stimulated by the positive modulator cinacalcet and
      inhibited by the negative modulator NPS 2143 in both CaSR-expressing cell types.
      Two positive modulators that bind in the receptor's Venus Fly Trap domain, l
      phenylalanine and S-methylglutathione, had no effect on p-CREB in HEK-CaSR cells,
      demonstrating the existence of pronounced signaling bias. Analysis of the
      signaling pathways using specific inhibitors demonstrated that phosphoinositide
      specific phospholipase C and conventional protein kinase C isoforms make major
      contributions to Ca(2+)o-induced p-CREB in both cell-types, suggesting key roles
      for Gq/11. In addition, in parathyroid cells but not HEK-CaSR cells, activation
      of p-CREB was dependent on Gi/o, demonstrating the existence of cell type
      specific signaling.

PMID- 23531617
TI  - The autonomic nervous system regulates postprandial hepatic lipid metabolism.
AB  - The liver is a key organ in controlling glucose and lipid metabolism during
      feeding and fasting. In addition to hormones and nutrients, inputs from the
      autonomic nervous system are also involved in fine-tuning hepatic metabolic
      regulation. Previously, we have shown in rats that during fasting an intact
      sympathetic innervation of the liver is essential to maintain the secretion of
      triglycerides by the liver. In the current study, we hypothesized that in the
      postprandial condition the parasympathetic input to the liver inhibits hepatic
      VLDL-TG secretion. To test our hypothesis, we determined the effect of selective
      surgical hepatic denervations on triglyceride metabolism after a meal in male
      Wistar rats. We report that postprandial plasma triglyceride concentrations were
      significantly elevated in parasympathetically denervated rats compared with
      control rats (P = 0.008), and VLDL-TG production tended to be increased (P =
      0.066). Sympathetically denervated rats also showed a small rise in postprandial
      triglyceride concentrations (P = 0.045). On the other hand, in rats fed on a six
      meals-a-day schedule for several weeks, a parasympathetic denervation resulted in
      >70% higher plasma triglycerides during the day (P = 0.001), whereas a
      sympathetic denervation had no effect. Our results show that abolishing the
      parasympathetic input to the liver results in increased plasma triglyceride
      levels during postprandial conditions.

PMID- 23531619
TI  - Expression of SHP-1 induced by hyperglycemia prevents insulin actions in
      podocytes.
AB  - Renal podocyte apoptosis is an early event of diabetic nephropathy progression.
      Insulin action is critical for podocyte survival. Previous studies demonstrated
      that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal
      cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1
      expression may affect insulin actions in podocytes. Type 1 diabetic Akita mice
      (Ins2(+/C96Y)) developed elevated foot process effacement and podocyte apoptosis
      compared with control littermate mice (Ins2(+/+)). In contrast to Ins2(+/+) mice,
      insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated
      kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita
      mice. This renal insulin resistance was associated with elevated SHP-1 expression
      in the glomeruli. Cultured podocytes exposed to high glucose concentration (HG;
      25 mM) for 96 h exhibited high levels of apoptotic markers and caspase-3/7
      enzymatic activity. HG exposure raised mRNA and protein levels of SHP-1 and
      reduced the insulin-signaling pathway in podocytes. Overexpression of dominant
      negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
      Elevated SHP-1 expression induced by high glucose levels was directly associated
      with insulin receptor-beta in vitro and in vivo to prevent insulin-stimulated Akt
      and ERK phosphorylation. In conclusion, our results showed that high levels of
      SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby
      contributing to diabetic nephropathy.

PMID- 23531618
TI  - Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator
      actions of insulin.
AB  - Obesity is characterized by a chronic proinflammatory state that leads to
      endothelial dysfunction. Saturated fatty acids (SFA) stimulate Toll-like
      receptors (TLR) that promote metabolic insulin resistance. However, it is not
      known whether TLR2 mediates impairment of vascular actions of insulin in response
      to high-fat diet (HFD) to cause endothelial dysfunction. siRNA knockdown of TLR2
      in primary endothelial cells opposed palmitate-stimulated expression of
      proinflammatory cytokines and splicing of X box protein 1 (XBP-1). Inhibition of
      unfolding protein response (UPR) reduced SFA-stimulated expression of TNFalpha.
      Thus, SFA stimulates UPR and proinflammatory response through activation of TLR2
      in endothelial cells. Knockdown of TLR2 also opposed impairment of insulin
      stimulated phosphorylation of eNOS and subsequent production of NO. Importantly,
      insulin-stimulated vasorelaxation of mesenteric arteries from TLR2 knockout mice
      was preserved even on HFD (in contrast with results from arteries examined in
      wild-type mice on HFD). We conclude that TLR2 in vascular endothelium mediates
      HFD-stimulated proinflammatory responses and UPR that accompany impairment of
      vasodilator actions of insulin, leading to endothelial dysfunction. These results
      are relevant to understanding the pathophysiology of the cardiovascular
      complications of diabetes and obesity.

PMID- 23531620
TI  - Estradiol effects on subcutaneous adipose tissue lipolysis in premenopausal women
      are adipose tissue depot specific and treatment dependent.
AB  - Estrogen has direct effects within adipose tissue and has been implicated in
      regional adiposity; however, the influence of estrogen on in vivo lipolysis is
      unclear. The purpose of this study was to investigate the effect of local 17beta
      estradiol (E(2)) on subcutaneous adipose tissue (SAT) lipolysis in premenopausal
      women. In vivo lipolysis (dialysate glycerol) was measured in 17 women (age 27.4
      +/- 2.0 yr, BMI 29.7 +/- 0.5 kg/m(2)) via microdialysis of abdominal (AB) and
      gluteal (GL) SAT. Glycerol was measured at baseline and during acute
      interventions to increase lipolysis including local perfusion of isoproterenol
      (ISO, beta-adrenergic agonist, 1.0 MUmol/l), phentolamine (PHEN, alpha-adrenergic
      antagonist, 0.1 mmol/l), and submaximal exercise (60% Vo(2peak), 30 min); all
      with and without coperfusion of E(2) (500 nmol/l). E(2) coperfusion blunted the
      lipolytic response to ISO in AB (E(2) 196 +/- 31%, control 258 +/- 26%, P =
      0.003) but not in GL (E(2) 113 +/- 14%, control 111 +/- 12%, P = 0.43) adipose
      tissue. At rest, perfusion of PHEN with ISO did not change dialysate glycerol.
      Submaximal exercise during ISO + PHEN increased dialysate glycerol in the AB (56
      +/- 9%) and GL (62 +/- 12%) regions. Probes perfused with E(2) during exercise
      and ISO + PHEN had an increased lipolytic response in AB (90 +/- 9%, P = 0.007)
      but a lower response in GL (35 +/- 7%, P = 0.05) SAT compared with no-E(2)
      conditions. E(2) effects on lipolysis are region specific and may work through
      both adrenergic and adrenergic-independent mechanisms to potentiate and/or blunt
      SAT lipolysis in premenopausal women.

PMID- 23531621
TI  - Rapid cortisol signaling in response to acute stress involves changes in plasma
      membrane order in rainbow trout liver.
AB  - The activation of genomic signaling in response to stressor-mediated cortisol
      elevation has been studied extensively in teleosts. However, very little is known
      about the rapid signaling events elicited by this steroid. We tested the
      hypothesis that cortisol modulates key stress-related signaling pathways in
      response to an acute stressor in fish liver. To this end, we investigated the
      effect of an acute stressor on biophysical properties of plasma membrane and on
      stressor-related protein phosphorylation in rainbow trout (Oncorhynchus mykiss)
      liver. A role for cortisol in modulating the acute cellular stress response was
      ascertained by blocking the stressor-induced elevation of this steroid by
      metyrapone. The acute stressor exposure increased plasma cortisol levels and
      liver membrane fluidity (measured by anisotropy of 1,6-diphenyl-1,3,5
      hexatriene), but these responses were abolished by metyrapone. Atomic force
      microscopy further confirmed biophysical alterations in liver plasma membrane in
      response to stress, including changes in membrane domain topography. The changes
      in membrane order did not correspond to any changes in membrane fatty acid
      components after stress, suggesting that changes in membrane structure may be
      associated with cortisol incorporation into the lipid bilayer. Plasma cortisol
      elevation poststress correlated positively with activation of intracellular
      stress signaling pathways, including increased phosphorylation of extracellular
      signal-related kinases as well as several putative PKA and PKC but not Akt
      substrate proteins. Together, our results indicate that stressor-induced
      elevation of plasma cortisol level is associated with alterations in plasma
      membrane fluidity and rapid activation of stress-related signaling pathways in
      trout liver.

PMID- 23531623
TI  - Step-up procedures for non-inferiority tests with multiple experimental
      treatments.
AB  - Non-inferiority (NI) trials are becoming more popular. The NI of a new treatment
      compared with a standard treatment is established when the new treatment
      maintains a substantial fraction of the treatment effect of the standard
      treatment. A valid NI trial is also required to show assay sensitivity, the
      demonstration of the standard treatment having the expected effect with a size
      comparable to those reported in previous placebo-controlled studies. A three-arm
      NI trial is a clinical study that includes a new treatment, a standard treatment
      and a placebo. Most of the statistical methods developed for three-arm NI trials
      are designed for the existence of only one new treatment. Recently, a single-step
      procedure was developed to deal with NI trials with multiple new treatments with
      the overall familywise error rate controlled at a specified level. In this
      article, we extend the single-step procedure to two new step-up procedures for NI
      trials with multiple new treatments. A comparative study of test power shows that
      both proposed step-up procedures provide a significant improvement of power when
      compared to the single-step procedure. One of the two proposed step-up procedures
      also allows the flexibility of allocating different error rates between the
      sensitivity hypothesis and the NI hypotheses so that the assignment of fewer
      patients to the placebo becomes possible when designing NI trials. We illustrate
      the new procedures using data from a clinical trial.

PMID- 23531624
TI  - Incidence of deep vein thrombosis after major spine surgeries with no mechanical
      or chemical prophylaxis.
AB  - STUDY DESIGN:  Retrospective cohort study. CLINICAL QUESTION:  What is the
      incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) after major
      spine surgery when no prophylactic measures were used? METHODS:  A prospective
      evaluation of 121 patients who underwent 128 major spine surgeries was conducted
      to determine the incidence of clinically identifiable DVT. As a matter of
      practice, no patient was given thromboprophylaxis, either mechanical or chemical.
      RESULTS:  Only one patient developed the signs and symptoms of DVT, which was
      further confirmed by a Doppler study. The overall incidence of DVT was 0.78%.
      There was no clinically evident case of PE. CONCLUSIONS:  Considering the low
      rate of incidence of DVT and PE, routine screening and prophylaxis for DVT
      appears unwarranted in major spine surgery. [Table: see text].

PMID- 23531622
TI  - The foamy virus Gag proteins: what makes them different?
AB  - Gag proteins play an important role in many stages of the retroviral replication
      cycle. They orchestrate viral assembly, interact with numerous host cell
      proteins, engage in regulation of viral gene expression, and provide the main
      driving force for virus intracellular trafficking and budding. Foamy Viruses
      (FV), also known as spumaviruses, display a number of unique features among
      retroviruses. Many of these features can be attributed to their Gag proteins. FV
      Gag proteins lack characteristic orthoretroviral domains like membrane-binding
      domains (M domains), the major homology region (MHR), and the hallmark Cys-His
      motifs. In contrast, they contain several distinct domains such as the essential
      Gag-Env interaction domain and the glycine and arginine rich boxes (GR boxes).
      Furthermore, FV Gag only undergoes limited maturation and follows an unusual
      pathway for nuclear translocation. This review summarizes the known FV Gag
      domains and motifs and their functions. In particular, it provides an overview of
      the unique structural and functional properties that distinguish FV Gag proteins
      from orthoretroviral Gag proteins.

PMID- 23531625
TI  - Urine Biomarkers Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney
      Injury Molecule-1 (KIM-1) Have Different Patterns in Heart Failure Exacerbation.
AB  - Individuals with acute heart failure exacerbation often experience a
      deterioration in renal function. We sought to determine whether this
      deterioration is ischemic in nature and detectable by sensitive urine biomarkers
      neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1
      (KIM-1). We measured serial biomarker levels and evaluated the associations of
      these biomarkers with renal recovery in a cohort of hospitalized patients with
      acute heart failure exacerbation.

PMID- 23531626
TI  - Practical single molecule force spectroscopy: how to determine fundamental
      thermodynamic parameters of intermolecular bonds with an atomic force microscope.
AB  - Single molecule force spectroscopy involves loading a chemical bond using an
      atomic force microscope and measuring the rupture forces required to break that
      bond. In 20 years since its inception this technique developed into a robust way
      to extract a nearly complete set of the information about the bond that includes
      the bond energy, the kinetic parameters of the bond, and the geometry of the
      transition state. In this article we review the basic physics of the
      measurements, the model that is used for data interpretation, and go over the
      ways to extract the bond information from the experimental data. We also discuss
      several practical aspects of the measurements that are helpful to the planning
      and analysis of single molecule force spectroscopy experiments.

PMID- 23531627
TI  - Melatonin is formed during winemaking at safe levels of biogenic amines.
AB  - The European Food Safety Authority (EFSA) has accepted health claims for the food
      constituent melatonin because scientific evidence shows that it is effective at
      reducing sleep onset latency, and that it alleviates subjective feelings of jet
      lag. According to risk assessment data published by EFSA in 2011, histamine and
      tyramine are the most toxic biogenic amines and the ones that most affect food
      safety. The potential formation of biogenic amines is a concern in fermented
      foods because of the intense microbial activity. Conversely, Saccharomyces
      cerevisiase produces melatonin during fermentation in the winemaking process.
      This study aims to evaluate the production of potentially healthy melatonin and
      toxic biogenic amines during the winemaking process. To this end, 11 biogenic
      amines (agmatine, cadaverine, histamine, methylamine, 2-phenylethylamine,
      putrescine, spermidine, spermine, tyramine, tryptamine and melatonin) have been
      monitored during the making of 5 monovarietal wines (Merlot, Palomino Fino,
      Syrah, Tempranillo and Tintilla de Rota). This paper shows that alcoholic and
      malolactic fermentation plays a crucial role in the formation of these compounds.
      Bioactive melatonin is formed at safe levels of the other biogenic amines.

PMID- 23531628
TI  - Do we know when to treat neonatal thrombocytopaenia?

PMID- 23531629
TI  - Gastroschisis, omphalocele or something else?

PMID- 23531631
TI  - Misleading features of neuroimaging and electroencephalography: insulinoma
      misdiagnosed as temporal lobe epilepsy.
AB  - Epilepsy is a common disorder but diagnosis remains largely clinical. Although
      MRI and EEG significantly aid the diagnosis of epilepsy, these techniques may
      also be misleading and indicate abnormalities not related to phenomenology.
      Consequences of erroneous diagnosis of epilepsy may lead to aggressive and
      escalating pharmacotherapy with potentially serious side effects. Metabolic
      disorders, which may mimic epilepsy, should always be considered as they are
      potentially curable and may be fatal if untreated. We report a case of an
      insulinoma, misdiagnosed as temporal lobe epilepsy. We highlight the risks
      associated with misinterpretation of neuroimaging and EEG and outline an approach
      to differentiate between symptoms of insulinoma or neuroglycopenia and temporal
      epileptic seizures.

PMID- 23531632
TI  - The role of glacial cycles in promoting genetic diversity in the Neotropics: the
      case of cloud forests during the Last Glacial Maximum.
AB  - The increasing aridity during the Last Glacial Maximum (LGM) has been proposed as
      a major factor affecting Neotropical species. The character and intensity of this
      change, however, remains the subject of ongoing debate. This review proposes an
      approach to test contrasting paleoecological hypotheses by way of their expected
      demographic and genetic effects on Neotropical cloud forest species. We reviewed
      48 paleoecological records encompassing the LGM in the Neotropics. The records
      show contrasting evidence regarding the changes in precipitation during this
      period. Some regions remained fairly moist and others had a significantly reduced
      precipitation. Many paleoecological records within the same region show
      apparently conflicting evidence on precipitation and forest stability. From these
      data, we propose and outline two demographic/genetic scenarios for cloud forests
      species based on opposite precipitation regimes: the dry refugia and the moist
      forests hypotheses. We searched for studies dealing with the population genetic
      structure of cloud forest and other montane taxa and compared their results with
      the proposed models. To date, the few available molecular studies show
      insufficient genetic evidence on the predominance of glacial aridity in the
      Neotropics. In order to disentangle the climatic history of the Neotropics, the
      present study calls for a general multi-disciplinary approach to conduct future
      phylogeographic studies. Given the contradictory paleoecological information,
      population genetic data on Neotropical cloud forest species should be used to
      explicitly test the genetic consequences of competing paleoecological models.

PMID- 23531630
TI  - ABA crosstalk with ethylene and nitric oxide in seed dormancy and germination.
AB  - Dormancy is an adaptive trait that enables seed germination to coincide with
      favorable environmental conditions. It has been clearly demonstrated that
      dormancy is induced by abscisic acid (ABA) during seed development on the mother
      plant. After seed dispersal, germination is preceded by a decline in ABA in
      imbibed seeds, which results from ABA catabolism through 8'-hydroxylation. The
      hormonal balance between ABA and gibberellins (GAs) has been shown to act as an
      integrator of environmental cues to maintain dormancy or activate germination.
      The interplay of ABA with other endogenous signals is however less documented. In
      numerous species, ethylene counteracts ABA signaling pathways and induces
      germination. In Brassicaceae seeds, ethylene prevents the inhibitory effects of
      ABA on endosperm cap weakening, thereby facilitating endosperm rupture and
      radicle emergence. Moreover, enhanced seed dormancy in Arabidopsis ethylene
      insensitive mutants results from greater ABA sensitivity. Conversely, ABA limits
      ethylene action by down-regulating its biosynthesis. Nitric oxide (NO) has been
      proposed as a common actor in the ABA and ethylene crosstalk in seed. Indeed,
      convergent evidence indicates that NO is produced rapidly after seed imbibition
      and promotes germination by inducing the expression of the ABA 8'-hydroxylase
      gene, CYP707A2, and stimulating ethylene production. The role of NO and other
      nitrogen-containing compounds, such as nitrate, in seed dormancy breakage and
      germination stimulation has been reported in several species. This review will
      describe our current knowledge of ABA crosstalk with ethylene and NO, both
      volatile compounds that have been shown to counteract ABA action in seeds and to
      improve dormancy release and germination.

PMID- 23531633
TI  - Effects of high thoracic epidural anesthesia on mixed venous oxygen saturation in
      coronary artery bypass grafting surgery.
AB  - BACKGROUND: To investigate possible effects of high thoracic epidural anesthesia
      (HTEA) on mixed venous oxygen saturation (SvO2) in coronary artery bypass
      grafting surgery (CABGS) MATERIAL AND METHODS: Sixty-four patients scheduled for
      CABGS were randomly assigned to either test (HTEA) or control group. Standard
      balanced general anesthesia was applied in both groups. Mean arterial blood
      pressure (MAP), heart rate (HR), oxygen saturation (SpO2), central venous
      pressure (CVP), cardiac output (CO), cardiac index (CI), systemic vascular
      resistance (SVR), pulmonary vascular resistance (PVR), mean pulmonary arterial
      pressure (PAP), pulmonary capillary wedge pressure (PCWP), pulmonary compliance
      (C), bispectral index (BIS), body temperature, SvO2, hematocrit values were
      recorded before induction. Postoperative hemodynamic changes, inotropic agent,
      need for vasodilatation, transfusion and additional analgesics, recovery score,
      extubation time, visual analogue scale (VAS) values, duration of stay in
      intensive care unit (ICU) and hospital were recorded. RESULTS: Study groups were
      similar in SpO2, CVP, PCWP, PAP, C, body temperature, BIS values, development of
      intraoperative bradycardia. In HTEA group, intraoperative MAP, SVR, PVR, need for
      transfusion were lower, whereas CO, CI, SvO2, hematocrit values were higher
      (p<0.05). Postoperative MAP, HR, hypertension development, need for
      vasodilatator, transfusion, analgesics, extubation time, recovery data, duration
      of stay in ICU, hospital were lower in HTEA group (p<0.05). VAS score decreased
      in 30 minutes and 12 hours following extubation in HTEA and control group,
      respectively. CONCLUSIONS: HTEA may improve balance between oxygen presentation
      and usage by suppressing neuroendocrin stress response; provide efficient
      postoperative analgesia, more stabile hemodynamic, respiratory conditions, lower
      duration of stay in ICU, hospital.

PMID- 23531634
TI  - Neurobiology of peripheral nerve injury, regeneration, and functional recovery:
      from bench top research to bedside application.
AB  - OBJECTIVES: We review the state-of-the-art neurobiology of nerve injury and
      regeneration, especially as it relates to return of useful function in patients
      who have sustained injuries to large nerve trunks such as the brachial plexus.
      METHODS: This review focuses on research conducted in our laboratory at Ochsner
      and at other laboratories related to the neurobiology of nerve injury with
      emphasis on how some of the key findings from animal research help us understand
      the pathophysiology of poor functional recovery after nerve injury. CONCLUSIONS:
      Published research on the neurobiology of nerve injury and regeneration strongly
      suggests that chronic Schwann cell denervation, chronic neuronal axotomy, and
      misdirection of regenerating axons into wrong endoneurial tubes are primarily
      responsible for poor functional recovery. The effect of muscle denervation
      atrophy is secondary. Experimental therapeutic strategies (which we are currently
      investigating in our laboratory at Ochsner) to combat these 3 neurobiologic
      phenomena have the potential to improve the return of function in patients who
      have sustained nerve injuries.

PMID- 23531635
TI  - The assessment of cytotoxic T cell and natural killer cells activity in residents
      of high and ordinary background radiation areas of Ramsar-Iran.
AB  - The effective radiation dose of human from natural sources is about 2.4 mSv/y and
      the dose limit for radiation workers is 20 mSv/y. Ramsar, a city in Iran, has
      been the subject of concern in the last forty years for a high level of radiation
      measured in some spots as high as 260 mSv/y. Carcinogenesis is one of the most
      studied effects of radiation especially in high doses. Recent studies showed that
      the high level of natural radiation received by inhabitants of this area,
      paradoxically don't have significant health effect. Natural killer (NK) cells and
      cytotoxic T cells are the most important cells in tumor immune surveillance and
      CD107a is a widely expressed intracellular protein located in the
      lysosomal/endosomal membrane. CD107a transiently located on the cell membrane can
      be used as a marker of CD8 + T cell degranulation following stimulation. It is
      also expressed, to a lower extent, on activated NK cells. In this study, 60
      healthy people were selected randomly and their consent obtained and confounding
      factors such as sex, age, life-styles was matched then the count of activated NK
      and CD8 + cells was compared in high and normal background radiation areas
      inhabitants of Ramsar. After filling the questionnaire and measurement of
      background radiation, blood samples of 30 healthy people from each region were
      analyzed immediately by means of flowcytometry. The leukocytes and their subsets
      were not significantly different between two groups and the count of active cells
      was higher in control group. The result shows that the changes in immune system
      occur due to radiation and maybe it is as a result of higher radiosensitivity of
      activated cells.

PMID- 23531636
TI  - Roots of beauty.

PMID- 23531637
TI  - Correlative microscopy methods that maximize specimen fidelity and data
      completeness, and improve molecular localization capabilities.
AB  - Correlative microscopy techniques interrogate biological systems more thoroughly
      than is possible using a single modality. This is particularly true if disparate
      data types can be acquired from the same specimen. Recently, there has been
      significant progress towards combining the structural information obtained from
      soft X-ray tomography (SXT) with molecular localization data. Here we will
      compare methods for determining the position of molecules in a cell viewed by
      SXT, including direct visualization using electron dense labels, and by indirect
      methods, such as fluorescence microscopy and high numerical aperture cryo-light
      microscopy. We will also discuss available options for preserving the in vivo
      structure and organization of the specimen during multi-modal data collection,
      and how some simple specimen mounting concepts can ensure maximal data
      completeness in correlative imaging experiments. 

PMID- 23531639
TI  - Predicting the Clinical Outcome of Allogeneic Hematopoietic Stem Cell
      Transplantation: The Long and Winding Road toward Validated Immune Biomarkers.
AB  - The clinical outcome of allogeneic hematopoietic stem cell transplantation (HSCT)
      is strongly influenced from the potential complications arising during the
      delicate phase of post-transplant immune restoration. The quantitative aspects of
      immune-cell repopulation after HSCT and the qualitative features their functional
      restitution have been extensively reported. Nevertheless, measurable immune
      biomarkers predicting the clinical outcome of HSCT await formal validation. The
      aim of this review is an appraisal of most studies published so far on the
      predictive value of different T and NK-cell biomarkers after HSCT with emphasis
      on defined thresholds endorsed by multivariate analysis.

PMID- 23531640
TI  - Patient expectations, outcomes and satisfaction: related, relevant or redundant?
AB  - STUDY DESIGN:  A prospective case series of patients undergoing lumbar spine
      surgery. OBJECTIVE:  Is there a correlation between patients' expectations before
      lumbar surgery, postoperative outcomes, and satisfaction levels? METHODS:  A
      prospective study of 145 patients undergoing primary, single-level surgery for
      degenerative lumbar conditions was conducted. Oswestry Disability Index, back
      Visual Analog Scale (VAS), and leg VAS were assessed preoperatively and at 6
      weeks and 6 months after surgery. Patients' expectations were measured
      preoperatively by asking them to score the level of pain and disability that
      would be least acceptable for them to undergo surgery and be satisfied.
      Satisfaction was assessed 6 weeks postoperatively with a Likert scale.
      Differences in patient expectations between actual and expected improvements were
      quantified. RESULTS:  Most patients had a clinically relevant improvement, but
      only about half achieved their expectations. Satisfaction did not correlate with
      preoperative pain or disability, or with patient expectation of improvement.
      Instead, satisfaction correlated with positive outcomes. CONCLUSIONS:  Patient
      expectations have little bearing on final outcome and satisfaction. [Table: see
      text].

PMID- 23531638
TI  - Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of
      breast cancer.
AB  - The transcription factors STAT3 and STAT5 play important roles in the regulation
      of mammary gland function during pregnancy, lactation, and involution. Given that
      STAT3 and STAT5 regulate genes involved in proliferation and survival, it is not
      surprising that inappropriate activation of STAT3 and STAT5 occurs commonly in
      breast cancer. Although these proteins are structurally similar, they have
      divergent and opposing effects on gene expression and cellular phenotype.
      Notably, when STAT5 and STAT3 are activated simultaneously, STAT5 has a dominant
      effect, and leads to decreased proliferation and increased sensitivity to cell
      death. Similarly, in breast cancer, activation of both STAT5 and STAT3 is
      associated with longer patient survival than activation of STAT3 alone.
      Pharmacological inhibitors of STAT3 and STAT5 are being developed for cancer
      therapy, though understanding the activation state and functional interaction of
      STAT3 and STAT5 in a patient's tumor may be critical for the optimal use of this
      strategy. 

PMID- 23531641
TI  - Posttraumatic pseudoaneurysm of popliteal artery following total knee
      arthroplasty.
AB  - We report a case of posttraumatic false aneurysm of popliteal artery after a
      total knee arthroplasty in an 82-year-old woman. This case is characterized by
      the distinct history of trauma to the popliteal fossa in the immediate
      postoperative period and the location of false aneurysm. In addition, the
      clinical symptoms were similar to those of deep vein thrombosis. The
      ultrasonographic examination and computed tomography (CT) angiography confirmed
      the diagnosis on 6(th) day after the surgery. Ultrasonographic examination 1 day
      later revealed no increase in the size of false aneurysm. She was treated with
      open surgical repair. Presenting the difficulty in the diagnosis, unusual
      location, etiology, and its management is the intention of this case report.

PMID- 23531642
TI  - Foraging by forest ants under experimental climatic warming: a test at two sites.
AB  - Climatic warming is altering the behavior of individuals and the composition of
      communities. However, recent studies have shown that the impact of warming on
      ectotherms varies geographically: species at warmer sites where environmental
      temperatures are closer to their upper critical thermal limits are more likely to
      be negatively impacted by warming than are species inhabiting relatively cooler
      sites. We used a large-scale experimental temperature manipulation to warm intact
      forest ant assemblages in the field and examine the impacts of chronic warming on
      foraging at a southern (North Carolina) and northern (Massachusetts) site in
      eastern North America. We examined the influence of temperature on the abundance
      and recruitment of foragers as well as the number of different species observed
      foraging. Finally, we examined the relationship between the mean temperature at
      which a species was found foraging and the critical thermal maximum temperature
      of that species, relating functional traits to behavior. We found that forager
      abundance and richness were related to the experimental increase in temperature
      at the southern site, but not the northern site. Additionally, individual species
      responded differently to temperature: some species foraged more under warmer
      conditions, whereas others foraged less. Importantly, these species-specific
      responses were related to functional traits of species (at least at the Duke
      Forest site). Species with higher critical thermal maxima had greater forager
      densities at higher temperatures than did species with lower critical thermal
      maxima. Our results indicate that while climatic warming may alter patterns of
      foraging activity in predictable ways, these shifts vary among species and
      between sites. More southerly sites and species with lower critical thermal
      maxima are likely to be at greater risk to ongoing climatic warming.

PMID- 23531643
TI  - A Rapid Stability-Indicating RP-HPLC Method for the Determination of Betaxolol
      Hydrochloride in Pharmaceutical Tablets.
AB  - A stability-indicating reversed-phase high performance liquid chromatography (RP
      HPLC) method was developed for the determination of betaxolol hydrochloride, a
      drug used in the treatment of hypertension and glaucoma. The desired
      chromatographic separation was achieved on a Nucleosil C18, 4 MUm (150 * 4.6 mm)
      column, using isocratic elution at a 220 nm detector wavelength. The optimized
      mobile phase consisted of a 0.02 M potassium dihydrogen phosphate: methanol
      (40:60, v/v, pH 3.0 adjusted with o- phosphoric acid) as solvent. The flow rate
      was 1.6 mL/min and the retention time of betaxolol hydrochloride was 1.72 min.
      The linearity for betaxolol hydrochloride was in the range of 25 to 200 MUg/mL.
      Recovery for betaxolol hydrochloride was calculated as 100.01%-101.35%. The
      stability-indicating capability was established by forced degradation experiments
      and the separation of unknown degradation products. The developed RP-HPLC method
      was validated according to the International Conference on Harmonization (ICH)
      guidelines. This validated method was applied for the estimation of betaxolol
      hydrochloride in commercially available tablets.

PMID- 23531644
TI  - Correlation of technical difficulty during embryo transfer with rate of clinical
      pregnancy.
AB  - AIM: To correlate the ease or difficulty of embryo transfer and blood at catheter
      tip with pregnancy rate when embryo transfer (ET) was performed by the same
      operator using soft catheter. MATERIALS AND METHODS: A retrospective analysis of
      342 patients who underwent in vitro fertilization or ICSI cycle from January 2008
      to December 2010 in a single centre was done. The type of transfer was divided
      into two groups: 'easy' or 'difficult'. Transfer was considered difficult when
      additional instrumentation was required or firmer catheter was used or required
      changing of catheter. Patients undergoing cryo-preserved ET were excluded from
      the study. RESULTS: On the day of transfer in 284 (83%) patients, ET was easy and
      difficulty was encountered in 58 (17%) patients. Blood at catheter was seen in
      101 (29.53%) patients. In the group of 58 difficult transfers, 10 pregnancies
      resulted with a clinical pregnancy rate of 17.2%, while 67 pregnancies resulted
      in 284 cycles of easy transfer with clinical pregnancy rate of 23.6% (P value =
      0.045). While no significant difference was seen in pregnancies with blood on
      outer catheter and blood less transfer, there was significant reduction in
      pregnancy rate when blood was present on catheter tip compared to bloodless
      transfer (13.3% v/s 24.1; P value = 0.032). CONCLUSION: Reduction in clinical
      pregnancy rate is seen with difficult ETs, more when blood is present at the
      catheter tip.

PMID- 23531646
TI  - [Biomarkers in allergy].

PMID- 23531647
TI  - [Biomarkers in childhood asthma].

PMID- 23531645
TI  - Short-term efficacy and tolerability of rufinamide adjunctive therapy in children
      with refractory generalised epilepsy.
AB  - We evaluated the efficacy and tolerability of rufinamide adjunctive therapy in
      children with refractory generalised epilepsy. The study cohort consisted of 20
      patients with Lennox-Gastaut syndrome, 5 with Dravet syndrome, and 28 with
      unclassified refractory generalised epilepsy. Patients with more than 50% seizure
      reduction at three and six months were defined as responders. The overall
      response rate was 37.7% at three months and 34.0% at six months. At three months,
      patients with Lennox-Gastaut syndrome (40.0%) and epilepsy with spasms/tonic
      seizures (38.5%) showed higher response rates than those with Dravet syndrome
      (20.0%) and epilepsy with myoclonic seizures (20.0%). High response rates in
      patients with Lennox-Gastaut syndrome (30.0%) and epilepsy with spasms/tonic
      seizures (38.5%) were sustained throughout the six-month study. The accuracy of,
      and differences between, responder rates should, however, be interpreted with
      caution due to the small number of patients. Overall, rufinamide appeared to be
      effective and reasonably well tolerated in this group of children with refractory
      generalised epilepsies, although a subgroup of patients with Dravet syndrome and
      epilepsy with myoclonic seizures were less responsive to rufinamide treatment.

PMID- 23531648
TI  - [Biomarker of atopic dermatits -focusing on serum TARC/CCL17 level as severity
      marker-].

PMID- 23531649
TI  - [The essence of "Asthma Prevention and Management Guideline 2012, Japan (JGL
      2012)" for adults].

PMID- 23531650
TI  - [Measures for anaphylaxis and role of Epipen(r)].

PMID- 23531651
TI  - [Immune semaphorins and allergic diseases].

PMID- 23531652
TI  - [Anaphylaxis and biphasic reaction in a children hospital].
AB  - BACKGROUND AND AIMS: Anaphylaxis is an acute multi-systemic and potentially fatal
      reaction, resulting from the exposure to antigens. There are few detailed reports
      of children with anaphylaxis. We studied the actual condition of an anaphylaxis
      including biphasic reaction. METHODS: This is a retrospective case study of
      children presenting to the Emergency Department of the National Center for Child
      Health and Development with anaphylaxis between 2002 and 2010. Etiology, age, sex
      ratio, clinical features, and management were examined. RESULTS: The median age
      of the patients was 36 months. Boys were predominant (63%). Seven cases developed
      anaphylactic shock, but all survived. As causes of anaphylaxis, food was
      identified in 85% of the patients, including eggs, dairy products and nuts, and
      drugs were identified in 3% of the patients. Initial symptoms consisted of
      mucocutaneous lesions (90%) and respiratory symptoms (71%). Epinephrine was given
      in 75 patients (22%). The biphasic anaphylactic reaction was observed in 3 out of
      the 340 cases (0.9%). In age, sex, grade and symptoms, there was no significant
      difference between patients with biphasic anaphylactic reaction and monophasic
      reaction. CONCLUSION: We clarified that the incidence of biphasic anaphylactic
      reaction was 0.9% in pediatric patients for the first time in Japan.

PMID- 23531653
TI  - [Assessment of climates affecting the control of bronchial asthma].
AB  - Pediatric patients with asthma are known to be exacerbated in autumn. On the
      other hand, there were few reports about the seasonal change of asthma control in
      the patients with adult asthma. In the present study, we conducted a
      questionnaire survey in 200 out patients with asthma to evaluate the climate
      which deteriorates asthma control. The patients whose asthmatic control was
      influenced by the specific climate were 141 (70.5%). The average age was younger
      and the percentage of moderate to severe was higher in the group whose asthma
      control was influenced by the specific climate than in the group whose asthma
      control was not influenced. The climate chosen the most as an inducer of asthma
      exacerbation was autumn, and the less was summer. Regarding to the severity, mild
      patients were tend to deteriorate in autumn, and moderate-to-severe patients were
      in winter. Meanwhile, the most climate chosen by the patients who had an
      obstructive ventilator disorder was winter, and the most climate chosen by the
      patients who did not have was autumn. These findings suggest that patients with
      asthma are influenced the most in autumn and severe asthma patients are in
      winter.

PMID- 23531654
TI  - [Evolution of ultrasonic indices of the heart and arteriovenous fistulas in
      patients on chronic haemodialysis].
AB  - The authors assessed the ultrasonic evolution of haemodynamics of arteriovenous
      fistulas (AVFs), cardiohaemodynamics, and the dimensions of the heart chambers in
      a total of thirty-five patients presenting with terminal chronic renal
      insufficiency (TCRI) and being on chronic haemodialysis (CHD). A further thirteen
      patients without TCRI composed the control group. The TCRI patients were
      subdivided into two groups: Group One (n=20) with a distal variant of the Cimino
      type AVF, 21 vascular accesses, and Group Two (n=15) with a proximal variant of
      AFV, 16 accesses using a synthetic vascular prosthesis (SVP). The terms of follow
      up of the TCRI patients were as follows: day 12, months 1, 3, 6 and 12 after
      creating the AVF. 12 days after creating the AVF there were no differences in the
      parameters of cardiohaemodynamics and the dimensions of the cardiac chambers
      between Group I and II. As compared with the control, the both groups of the
      patients with TCRI at these terms demonstrated increased sizes of the left
      ventricle (LV). The dynamic follow up during the subsequent periods showed that
      Group One and Group Two patients had no statistically significant differences in
      the parameters studied, however, patients of the both study groups were found to
      have a trend toward increased dimensions of the right chambers of the heart, not
      exceeding the limits of the norm of these indices. The volumetric velocity of the
      blood flow (BFVV) through the Cimino-type AVF during 12 months had a tendency
      towards a graduate growth up to 800 ml/min, whereas the proximal fistulas were
      characterized by stable indices of the BFVV at a level of 900 ml/min. The
      revealed alterations in the right chambers of the heart after creating the AVF
      required no surgical correction of the volumetric blood flow through the AVF
      during the follow up period up to 12 months.

PMID- 23531655
TI  - [Assessment of clinical and antiaggregation efficacy of generic clopidogrel
      'Egithromb' in roentgenosurgical practice].
AB  - The authors studied efficacy of the generic clopidogrel Egithromb manufactured by
      EGIS PHARMACEUTICALS (Hungary) based on clinical data and parameters of light
      aggregometry in a total of 30 patients subjected to planned subcutaneous coronary
      intervention for stable angina pectoris. It was noted that the generic
      clopidogrel Egithromb possesses clinical efficacy, manifesting in the lack of
      early thromboses of the stents and relapses of angina pectoris during the first
      month of treatment. The findings obtained by light aggregometry strongly
      suggested a significant decrease in aggregation with a dose of ADP 1.25 mcg/ml in
      87.33% of patients, with the target values of the index less than 25% were
      obtained in 100% of cases. It was determined that the agent possesses high
      efficacy in aspirin-resistant patients and in the presence of thrombinemia. There
      were neither side events of therapy nor haemorrhagic complications in the present
      study during treatment.

PMID- 23531656
TI  - [Treatment for chronic obliterating diseases of lower limb arteries].
AB  - The work is dedicated to a new method of treatment for chronic obliterating
      diseases of lower limb arteries - cardiosynchronized sequential antegrade
      pneumocompression. The author describes the basic principles of the method, its
      physiological effects, and the results of treatment on volunteers.

PMID- 23531657
TI  - [Noninvasive assessment of functional competence of the radial artery as a
      possible vascular graft for coronary artery bypass grafting].
AB  - Described herein is a variant of surgical treatment of a patient presenting with
      type A aortic dissection extending to the brachiocephalic branches accompanied by
      thrombosis of the false channel of the latter. In the rare cases in dissection
      and thrombosis of the brachiocephalic branches for adequate protection of the
      body (systemic protection) it is necessary to use bidirectional arterial
      perfusion under the conditions of moderate hyperthermia: through a preliminarily
      sewn into the carotid artery prosthesis - perfusion of the brain, through
      cannulated aortic arch or femoral artery - body perfusion.

PMID- 23531658
TI  - [Outcomes of hybrid operations in multi storeyed lesions of arteries of the
      aortoiliac and femoropopliteal segments].
AB  - The work was aimed at analysing immediate and remote outcomes of hybrid
      operations in storey atherosclerotic lesions of the aortoiliac and
      femoropopliteal segments. Over the period from 1997 to 2012 hybrid operations
      were performed in a total of 224 patients presenting with multi-storeyed lesions
      of iliac and lower-limb arteries, classified as TASC A, B, C, and D. The
      operations were carried out at departments of vascular surgery of Clinical
      Hospital No 83 of the Federal Biomedical Agency of Russia and the Centre of
      Cardiovascular and Endovascular Surgery of Clinical Hospital No 119 of the
      Federal Biomedical Agency of Russia. All operations were simultaneous. The
      patients were subdivided into groups according to the character of intervention
      on iliac arteries: 1 - balloon angioplasty of iliac arteries, 2 - stenosing of
      iliac arteries, 3 - loop endarterectomy from iliac arteries followed by
      implantation of a covered stent into the zone of rupture of the intimal cylinder.
      In all cases the interventions of the arteries of the aortoiliac segment were
      combined with various open surgical reconstructions of the femoropopliteal
      segment. Technical success amounted to 99.1%. Interventional complications of the
      endovascular stage requiring conversion occurred in 2 cases. The immediate period
      complications influencing patency of the reconstructions performed were noted in
      10 (4.5%) patients. Patency on the hospital stage with the deduction of cases of
      technical failures amounted to 98.6%. The remote results were followed up during
      5 years in 76.5% of patients. Five-year primary assisted patency of the
      aortoiliac zone amounted to: in group 1 - 79.2%, in group 2 - 77.9%, and in group
      3 - 89.4%. Five-year assisted patency of the femoropopliteal segment amounted to:
      for EAE of the common femoral artery - 98.2%, for profundoplasty - 100%, femoral
      proximal popliteal bypass grafting - 77.3%, femoral distal popliteal bypass
      grafting - 74.1%, femoral-tibial bypass grafting - 61.4%. There were no
      statistically significant differences in patency of the reconstructions of the
      femoropopliteal segment depending upon the type of intervention on the aortoiliac
      segment.

PMID- 23531659
TI  - [Angiographic characteristics of the lesion, influencing the choice to perform
      either direct or indirect endovascular revascularization for critical ischaemia
      of the lower limbs].
AB  - AIM: to determine which angiographic characteristics of a lesion of lower limb
      arteries are independent predictors of the possibility to re-establish the direct
      blood flow along the angiosomic (in relation to the trophic defect) artery.
      MATERIAL AND METHODS: we carried out a retrospective analysis of angiograms of
      192 patients with degree IV peripheral arterial disease according to A.V.
      Pokrovky's classification, with restored free blood flow to the foot at least
      along one femoral artery by means of balloon angioplasty. All patients were
      subdivided into two groups: the group of direct revascularization (84 patients)
      and the group of indirect revascularization (108 patients). The compared groups
      reliably did not differ by the clinical characteristics and the stage of the
      trophic lesion (male gender, prevalence of diabetes mellitus and mean age
      amounted to: 45%, 73% and 71 years versus 39%, 77% and 69 years, respectively).
      However, in the group of direct revascularization more frequently were
      encountered lesions of the toes (75% vs 55%, p = 0.005), while in the group of
      indirect revascularization prevailing were lesions of the heel region (7% vs 29%,
      p=0.0002). RESULTS: the statistical analysis showed that independent predictors
      for a possibility of performing direct revascularization were as follows: total
      occlusion of the angiosomic artery on the foot (risk ratio (95% CI) = 0.10 (0.03
      0.31), p =0.0001), blind (without stump) occlusion in the site of the origin of
      the angiosomic artery on the crus or foot (risk ratio (95% CI)=0.41 (0.19-0.90,
      p=0.03), and total occlusion of the trifurcation of the popliteal artery (risk
      ratio (95% CI) = 028 (0.09-0.81), p=0.02). CONCLUSION: in the presence of the
      above enumerated angiographic characteristics of the lesions of lower limb
      arteries it is appropriate to initially consider a possibility of performing
      indirect revascularization.

PMID- 23531660
TI  - [Antegrade catheterization of the brachial artery during treatment of
      arteriovenous angiodysplasia of the forearm and hand].
AB  - The authors share herein their experience with an antegrade brachial access for
      treatment of patients presenting with arteriovenous angiodysplasia localizing on
      the distal portions of the upper limbs, also describing the choice of the site
      for puncture and the technique of antegrade catheterization of the brachial
      artery. This is followed by reporting the results of successful use of this
      access in a total of 27 patients. The access is simple to create, making it
      possible to easily perform the intervention using instruments of standard length.
      It is also safe, requires no bed rest in the postoperative period, and is well
      tolerated by the patients.

PMID- 23531661
TI  - The role of carotid stenting for the treatment of carotid disease.
AB  - Carotid artery occlusion is one of the most frequent and treatable causes of
      ischemic strokes. Although carotid endarterectomy (CEA) is recognized as the gold
      standard for treating symptomatic, severe carotid stenosis, investigations have
      sought to demonstrate the efficacy of carotid angioplasty and stenting (CAS) as a
      potential alternative to surgical management. Patient selection is crucial in the
      judicious application of CAS and CEA. Recent investigations have emphasized the
      potential of endovascular procedures to complement rather than replace surgical
      techniques for treating a wide spectrum of carotid disease.

PMID- 23531662
TI  - [Role of optical properties of the venous wall for endovenous laser
      obliteration].
AB  - Presented herein are the results of studying the optical density of water, blood,
      and venous-wall tissue for various-wavelength laser radiation, with determining
      the peaks of absorption of radiation by the above-mentioned media. The absorption
      peaks in water and blood correspond to wavelengths of 1,450 and 1,935 nm,
      respectively. Peaks of absorption in the venous-wall tissue are within the
      intervals equaling 650-950 nm, 1,445-1,455 nm, and more than 1,900 nm. Also
      determined was the optical density of the veins for the most frequently used in
      clinical practice wavelengths, i. e. 1,030 and 1,470 nm, with the calculation of
      the portion of the absorbed energy depending on thickness of the layer of the
      absorbing substance. Based on the obtained findings, a conclusion was drawn on
      better utilization of the energy of one-and-a-half-micron range laser radiation
      and on its preferable use for endovenous laser obliteration (EVLO).

PMID- 23531663
TI  - [Bioflavonoids and their significance in angiology: focus on diosmin].
AB  - The article deals with historical information dedicated to the discovery of
      bioflavonoids and their effect on the human cardiovascular system, also
      considering the modern classification of phlebotrophic agents, followed by
      generalization and analysis of their mechanisms of action, as well as detailed
      discussion of different forms of diosmin. Summing up contains generalization of
      the Russian, European, and American guidelines on using phlebotrophic drugs for
      various forms and stages of chronic venous diseases.

PMID- 23531664
TI  - [Experience in using Antistax(r) in patients with lower limb chronic venous
      insufficiency and accompanying arterial hypertension].
AB  - The main pathogenetic causes of the development of lower limb chronic venous
      insufficiency (CVI) are associated with hypertension in the inferior vena cava,
      venous stasis, and ischaemia of the vascular wall. Alterations in
      microcirculation responsible for the metabolic and trophic processes of the
      venous wall appear on the background of change in the macrocirculatory bed. A
      considerable role of the venous endothelial dysfunction was noted. Prescription
      of phleboprotectors and phlebotonics is of fundamental importance. Efficacy of
      Antistax makes it possible to recommend its use in combined therapy of various
      aetiology and various-grade CVI.

PMID- 23531665
TI  - [Surgical therapeutic decision-making in elderly patients with heart valvular
      defects combined with lesions of coronary and brachiocephalic arteries].
AB  - Due to considerable incidence of combined cardiac and vascular pathology in
      elderly and aged patients with heart valve defects, of special importance is the
      problem regarding surgical therapeutic decision-making. The present article is
      aimed at considering the problems concerning possibility and feasibility of
      stagewise or simultaneous surgical correction in patients diagnosed as having
      cardiac valve defect and haemodynamically significant lesions of coronary and/or
      brachiocephalic arteries based on generalizing the results of international
      studies.

PMID- 23531666
TI  - [Assessment of remote survival in patients with peripheral atherosclerosis after
      endured interventions on coronary arteries].
AB  - The article deals with a retrospective analysis of the risk for the development
      of unfavourable outcomes in vascular patients after interventions on coronary
      arteries versus those without them. The authors assessed remote survival in
      patients with atherosclerotic lesions of the coronary and vascular beds as
      compared with isolated coronary artery bypass grafting. All patients were at the
      Federal Centre for Cardiovascular Surgery from October 2008 to December 2009 and
      later on underwent planned examination at a polyclinic. The patients were
      subdivided into the following groups: Group 1 comprised a total of 131 vascular
      patients undergoing single-stage or stepwise operations on coronary arteries (CA)
      (CABG + peripheral vascular disease). They were also subjected to interventions
      on the abdominal aorta, carotid arteries and lower-limb arteries. Group 2 (PVD)
      comprised a total of 153 vascular patients without myocardial revascularization
      with documented indications for coronary artery bypass grafting according to the
      findings of coronography and noninvasive methods of examination. Group 3 (CABG)
      consisted of 258 patients without symptoms of peripheral atherosclerosis who
      underwent CABG and were examined at a polyclinic over the same period of time as
      the study groups. The findings of examination confirmed the world-literature
      discussed proposition suggesting that preventive CABG considerably improves the
      long-term prognosis for vascular patients. This is of special importance taking
      into consideration that a preventive intervention on CA brings no additional risk
      of operative treatment.

PMID- 23531667
TI  - [Oxygen status of the brain and quality of life in remote terms after carotid
      endarterectomy].
AB  - The authors assessed efficacy of eversion carotid endarterectomy and its effect
      on dynamics of the oxygen status of the brain and quality of life of 122 patients
      at terms from 6 months to 4 years after surgical treatment. It was shown that
      positive effect from the operation is preserved in 94% of cases, lethality in the
      remote terms amounted to less than 1%, acute impairment of cerebral circulation
      on the side of revascularization was registered in 2.5% of cases,
      haemodynamically significant restenoses in the zone of vascular reconstruction in
      2.5%. Revascularization results in increased efficacy of the oxygen supply of the
      brain and the level of quality of life, including in patients with a history of
      ischaemic stroke.

PMID- 23531668
TI  - [Efficacy of carotid endarterectomy in patients with stenosis of carotid arteries
      and acute vision impairment].
AB  - The article deals with comparing efficacy (improved function of the eye) of
      surgical and conservative treatment of patients presenting with atherosclerotic
      stenosis of carotid arteries and acute vision disorders. The surgery group
      (carotid endarterectomy) comprised a total of 49 patients and the conservative
      treatment group consisted of 50 subjects. Methods of examination included:
      determining visual acuity (VA), autorefractometry, direct and reverse
      ophthalmoscopy under the conditions of mydriasis, contactless computed
      tomography, computer-assisted static perimetry, assessment of the functional
      state of the optic nerve (ON) with determination of the parameters of the
      threshold of electric sensitivity and lability of the optic nerve by phosphene,
      ultrasonographic scanning of ophthalmic arteries and carotid arteries. The terms
      of examination were as follows: at baseline, one months and one year after
      surgery or conservative treatment. The results (by the groups) were as follows:
      in amaurosis fugas - improvement of VA by 0.1 and more: 15 and 0 (p<0.001),
      disappearance of fits of amaurosis fugas: 16 and 3 (p<0.001), widening of the
      fields of vision: 16 and 0 (p<0.001), improvement of the condition of the optic
      nerve: 16 and 0 (p<0.001), maximal increase of systolic blood velocity in the
      arteries of the eye (Vs): by 30% and 0. In occlusion of the central retinal
      artery and its branches - improvement of VA by 0.1 and more: 8 and 1 (p=0.005),
      widening of the fields of vision: 6 and 2 (p = 0.112), improved condition of the
      optic nerve: 14 and 0 (p<0.001), increase in the Vs: 40% and 0. In acute
      ischaemic neuropathy - improvement of VA by 0.1 and more: 9 and 2 (p<0.001),
      widening of the fields of vision: 9 and 3 (p=0.004), improved condition of the
      optic nerve: 11 and 0 (p<0.001), increased Vs: 40% and 0. Total - improvement of
      VA by 0.1 and more: 32 and 2 (p<0.001), widening of the fields of vision: 31 and
      8 (p<0.001), improved condition of the optic nerve: 41 and 0 (p<0.001), Vs
      increase: 40% and 0. Carotid endarterectomy effectively improves the functional
      state of the eye in patients with stenosis of carotid arteries and acute vision
      impairments.

PMID- 23531669
TI  - [Hybrid operation for a posttraumatic saccular aneurysm of the aortic arch].
AB  - The article deals with a case report of successful hybrid surgical treatment of a
      patient presenting with a posttraumatic large false saccular aneurysm of the
      aortic arch with mediastinal displacement and compression of the left recurrent
      laryngeal nerve and trachea. The patient was subjected to a hybrid operation, i.
      e., bypass grafting of the brachiocephalic trunk and the left common carotid
      artery with a bifurcation prosthesis from the ascending aorta through sternotomy,
      carotid-vertebral and carotid-subclavian bypass grafting on the left in a
      combination with endoprosthetic repair of the aortic arch with the stent graft
      Valiant Thoracic 40 * 224 mm (VAMF 4040c200TE) manufactured by the Medtronic
      Company. The postoperative period was uneventful followed by rather rapid
      rehabilitation of the patient. One month after the operation, the clinical state
      improved considerably. His voice restored virtually completely, and
      breathlessness disappeared. According to the findings of MSCT angiography, the
      aneurysmatic cavity is thrombosed, with the stent graft showing no evidence of
      either dislocation or endoleak. The bifurcation bypass graft is functioning.
      According to the data of duplex scanning, the anastomoses established on the neck
      are patent.

PMID- 23531670
TI  - [Dynamics of lung perfusion after pulmonary thromboendarterectomy in patients
      with chronic postembolic pulmonary hypertension].
AB  - Perfusion scintigraphy of the lungs is used as screening in order to confirm
      thrombormbolic genesis of pulmonary hypertension. Meanwhile, perfusion
      scintigraphy is a non-invasive and objective method of assessing haemocirculation
      in the pulmonary tissue. Using the quantitative method of calculation of the
      perfusion deficit, one may judge about efficiency of the treatment performed and
      to assess the dynamics of the state of the micro- circulatory bed of the lung. We
      examined a total of 53 patients presenting with chronic postembolic pulmonary
      hypertension, who underwent pulmonary thromboendarterectomy. Pulmonary tissue
      blood flow was assessed by means of perfusion scintigraphy prior to operation,
      and in the early postoperative (3 weeks after operation) and remote (6 months and
      more) periods. Analysing the values of perfusion deficit in patients depending on
      the pulmonary hypertension degree we revealed close correlation dependence
      between the perfusion deficit and pulmonary hypertension, i. e., increased
      pressure in the pulmonary artery was accompanied by a decreased defect of lung
      perfusion according to the findings of perfusion scintigraphy. Analyzing the
      findings of perfusion scintigraphy in patients presenting with chronic
      postembolic pulmonary hypertension prior to surgery, in the immediate and remote
      postoperative periods in all groups showed a statistically significant decrease
      in the perfusion deficit. It was demonstrated that the method of perfusion
      pulmonary scintigraphy reliably reflects the alterations in the pulmonary tissue
      perfusion after lung pulmonary thromboendarterectomy, thereby reflecting
      efficiency of surgical treatment. With the initially pronounces pulmonary
      hypertension, improvement of lung perfusion obtained at the hospital stage also
      continues in the remote period.

PMID- 23531671
TI  - [Complications after reconstructive operations on major arteries of lower limbs
      and methods of correction thereof].
AB  - The present study was aimed at revealing and examining the causes of specific
      complications after reconstructive vascular operations in the aortic-iliac
      femoral zones. The study comprised a total of 155 patients, with the period of
      postoperative follow up amounting to 3 years. Thirty-nine patients were operated
      on for various specific complications within the terms from 1 to 3 years. The
      results of the study showed clear-cut relationship between the development of
      complications and progression of the underlying disease. Satisfactory results
      after secondary interventions were obtained in patients with good state of the
      distal bed and operated on at early terms after complications.

PMID- 23531672
TI  - [Using femoral autovein in reconstruction of the aortoiliac segment in patients
      with high risk of infectious complications].
AB  - AIM: To analyse the results of using a femoral vein for reconstruction of the
      aortoiliac segment. MATERIAL AND METHODS: We performed a total of 10
      reconstructions of the aortoiliac segment using a femoral autovien. The patients'
      average age amounted to 58,8+/-4,5 years. RESULTS: The patients were subdivided
      into 2 groups, with Group 1 consisting of 5 patients operated on for complication
      of aortoiliac reconstruction using an artificial graft. The grafts were retrieved
      followed by repeat prosthetic repair with the femoral vein. All cases showed
      satisfactory revascularization of the limb. Venous outflow impairments after
      removal of the femoral vein were inconsiderable. One patient died. Group 2
      comprised 5 patients initially operated on for critical ischaemia of the lower
      limbs with purulent necrotic lesions. Revascularization with a femoral vein was
      performed in all cases resulting in re-establishment of blood circulation. The
      procurement of the vein was followed by pronounced impairments of the lymphatic
      and venous outflow. CONCLUSION: Primary autovenous reconstruction of the
      aortoiliac segment in patients with purulent necrotic impairments is less risky
      from the point of view of late complications than implantation of an artificial
      graft and is more advantageous from the point of view of quality of life than
      primary high amputation.

PMID- 23531673
TI  - [Experience with osteosynthesis of the sternum after heart surgery in patients
      with limited physical abilities].
AB  - At the Department of Heart Surgery of the A. V. Vishnevsky Institute of Surgery
      in seven patients with limited physical abilities and having to ambulate on
      crutches for osteosynthesis of the sternum after cardiosurgical interventions we
      used Ti-Ni fixating cramps with self-regulating compression. This technique
      provided reliable fixation of the sternum even in the early postoperative period
      in patients with elevated loading on the shoulder gridle. On day 2-3 after the
      surgical intervention all patients began to observe the standard motor regimen,
      i.e., ambulation on crutches. The possibility of early activation in the
      initially severe cohort of patients with multifocal atherosclerosis and
      accompanying diseases was one of the factors of an uneventful course of the
      postoperative period and rapid rehabilitation. Neither sternal instability nor
      infectious complications during the in-hospital period were observed.

PMID- 23531674
TI  - [Transcutaneous coronary intervention accompanied by biventricular circulatory
      support and combined with extracorporeal membranous oxygenation].
AB  - In a multiple-vessel lesion of the coronary bed, pronounced accompanying
      pathology, low ejection fraction of the left ventricle, obesity, previously
      performed operation of coronary aortic bypass grafting may be causes of refusal
      from revascularization by means of coronary bypass grafting. A transcutaneous
      coronary intervention (TCI) in this patient cohort is also associated with the
      risk of an unfavourable outcome in case of a technically complicated procedure
      and a large volume of the myocardium supplied with blood by the target arteries.
      Haemodynamic support of such high-risk TCI by means of intra-aortic balloon
      contrapulsation or a left-ventricle assist device is associated with a series of
      shortcomings which are removed by means of a biventricular bypass used in a
      combination with extracorporeal membranous oxygenation. This article deals with a
      case report of successful stenting of the unprotected trunk of the left coronary
      artery and the right coronary artery in the conditions of a mechanical
      biventricular bypass.

PMID- 23531675
TI  - [A case of successful surgical treatment of a 79-year-old patient with gigantic
      abdominal infrarenal aortic aneurysm and cachexy].
AB  - Presented in the article is a clinical case report concerning successful surgical
      management of a 79-year-old male patient with a gigantic aneurysm of the
      infrarenal portion of the abdominal aorta on the background of pronounced
      cachexia. The patient was subjected to prosthetic repair of the abdominal aorta.
      After treatment of exacerbation of chronic bronchitis in the postoperative period
      and normalization of the intestinal function, the patient was discharged home in
      a satisfactory condition.

PMID- 23531676
TI  - [Resection of leiomyosarcoma of the inferior vena cava].
AB  - Experience in treatment of leiomyosarcoma of the retrohepatic segment of the
      inferior vena cava at any separately taken clinic is scarce. Given a rare nature
      of the pathology involved, whose diagnosis and management require joint
      participation of various-specialty physicians, we have considered it wise to
      present our own clinical case report.

PMID- 23531677
TI  - [Embolism of the aortic bifurcation and major arteries of limbs: lessons of the
      past and present-day trends in solving the problem concerned].
AB  - The works deals with a retrospective analysis of the medical records of the
      Clinic of General Surgery of the North-West State Medical University named after
      I.I. Mechnikov on treatment of patients presenting with embolism of the aorta and
      major arteries over 40 years. All in all, over the period from 1971 to 2010 a
      total of 3,110 patients with embolism of the aorta and major arteries underwent
      consultations and were operated on. To the present-day trends in surgery of
      embologenic arterial obstruction one should first of all refer a decrease in the
      number of patients with embolism of the aorta and major arteries of the limbs,
      which may be related to achievement in modern cardiology and cardiosurgery in
      treatment of patients with cardiovascular diseases - potential sources of
      arterial embolism. Besides, there occurred considerable changes in the structure
      of embologenic diseases, in favour of an increased number of people suffering
      from CAD, which to e certain degree modified the incidence of lesions of various
      vascular basins. Thus, the number of embolisms of proximal portions of the
      vascular bed decreased considerably. This is largely related to a decrease in the
      number of patients presenting with decompensated ischaemia of extremities. 86.9%
      of patients were subjected to emergency operations. An increased number of people
      with atherosclerosis of peripheral arteries required widening of indications for
      performing reconstructive-and-plastic operative interventions. Experience of the
      Clinic shows that a timely performed revascularizing operation, including a
      reconstructive on, application of modern methods of prevention of ischaemic
      syndrome, carrying out comprehensive rehabilitation measures in the postoperative
      period made it possible to considerably improve the immediate results of
      treatment. While during the first 20 years a total lethality rate amounted to
      18.8% with the postoperative one equalling 17.1%, these parameters over the past
      10 years were 8.8% and 6.9%, respectively.

PMID- 23531679
TI  - Rapid classification of pharmaceutical ingredients with Raman spectroscopy using
      compressive detection strategy with PLS-DA multivariate filters.
AB  - Identifying pharmaceutical ingredients is a routine procedure required during
      industrial manufacturing. Here we show that a recently developed Raman
      compressive detection strategy can be employed to classify various widely used
      pharmaceutical materials using a hybrid supervised/unsupervised strategy in which
      only two ingredients are used for training and yet six other ingredients can also
      be distinguished. More specifically, our liquid crystal spatial light modulator
      (LC-SLM) based compressive detection instrument is trained using only the active
      ingredient, tadalafil, and the excipient, lactose, but is tested using these and
      various other excipients; microcrystalline cellulose, magnesium stearate,
      titanium (IV) oxide, talc, sodium lauryl sulfate and hydroxypropyl cellulose.
      Partial least squares discriminant analysis (PLS-DA) is used to generate the
      compressive detection filters necessary for fast chemical classification.
      Although the filters used in this study are trained on only lactose and
      tadalafil, we show that all the pharmaceutical ingredients mentioned above can be
      differentiated and classified using PLS-DA compressive detection filters with an
      accumulation time of 10ms per filter.

PMID- 23531678
TI  - UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores.
AB  - The effect of UV irradiation on replicating cells during interphase has been
      studied extensively. However, how the mitotic cell responds to UV irradiation is
      less well defined. Herein, we found that UV-C irradiation (254 nm) increases
      recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore
      during metaphase, suggesting that the spindle assembly checkpoint (SAC) is
      reactivated. In accordance with this, cells exposed to UV-C showed delayed
      mitotic progression, characterized by a prolonged chromosomal alignment during
      metaphase. UV-C irradiation also induced the DNA damage response and caused a
      significant accumulation of gamma-H2AX on mitotic chromosomes. Unexpectedly, the
      mitotic delay upon UV-C irradiation is not due to the DNA damage response but to
      the relocation of Mps1 to the kinetochore. Further, we found that UV-C
      irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora
      B is indispensable for full recruitment of Mps1 to the kinetochore during both
      prometaphase and metaphase. Taking these findings together, we propose that UV
      irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling
      cascade, which exerts its role through promoting the association of Mps1 with the
      kinetochore in metaphase.

PMID- 23531680
TI  - Effects of sutures and fontanels on MEG and EEG source analysis in a realistic
      infant head model.
AB  - In infants, the fontanels and sutures as well as conductivity of the skull
      influence the volume currents accompanying primary currents generated by active
      neurons and thus the associated electroencephalography (EEG) and
      magnetoencephalography (MEG) signals. We used a finite element method (FEM) to
      construct a realistic model of the head of an infant based on MRI images. Using
      this model, we investigated the effects of the fontanels, sutures and skull
      conductivity on forward and inverse EEG and MEG source analysis. Simulation
      results show that MEG is better suited than EEG to study early brain development
      because it is much less sensitive than EEG to distortions of the volume current
      caused by the fontanels and sutures and to inaccurate estimates of skull
      conductivity. Best results will be achieved when MEG and EEG are used in
      combination.

PMID- 23531682
TI  - Evaluating the effect of ultrasmall superparamagnetic iron oxide nanoparticles
      for a long-term magnetic cell labeling.
AB  - In order to evaluate the long-term viability, the iron content stability, and the
      labeling efficiency of mammalian cells using magnetic cell labeling; dextran
      coated ultrasmall superparamagnetic iron oxide (USPIOs) nanoparticles with plain
      surfaces having a hydrodynamic size of 25 nm were used for this study. Tests were
      carried out in four groups each containing 5 flasks of 5.5 * 10(6) AD-293
      embryonic kidney cells. The cell lines were incubated for 24 h using four
      different iron concentrations with and without protamine sulfate (Pro), washed
      with phosphate-buffered saline (PBS) and centrifuged three times to remove the
      unbounded USPIOs. Cell viability was also verified using USPIOs. There were no
      significant differences in the cell viability between the control group of cells
      and those groups with iron uptake at the specified iron concentrations. The
      average iron uptake ratio compared to that of the control group was (114 +/- 1).
      The magnetic resonance images (MRI) at post-labeling day 1 and day 21 showed (75
      +/- 4)% and (22 +/- 5)% signal decrements compared to that of the control,
      respectively. The Perl's Prussian blue test showed that 98% of the cells were
      labeled, and the iron concentration within the media did not affect the cell iron
      uptake. Magnetic cellular labeling with the USPIO-Pro complex had no short or
      medium term (3 weeks) toxic effects on AD-293 embryonic kidney cells.

PMID- 23531681
TI  - Microglia activation as a biomarker for traumatic brain injury.
AB  - Traumatic brain injury (TBI) has become the signature wound of wars in
      Afghanistan and Iraq. Injury may result from a mechanical force, a rapid
      acceleration-deceleration movement, or a blast wave. A cascade of secondary cell
      death events ensues after the initial injury. In particular, multiple
      inflammatory responses accompany TBI. A series of inflammatory cytokines and
      chemokines spreads to normal brain areas juxtaposed to the core impacted tissue.
      Among the repertoire of immune cells involved, microglia is a key player in
      propagating inflammation to tissues neighboring the core site of injury.
      Neuroprotective drug trials in TBI have failed, likely due to their sole focus on
      abrogating neuronal cell death and ignoring the microglia response despite these
      inflammatory cells' detrimental effects on the brain. Another relevant point to
      consider is the veracity of results of animal experiments due to deficiencies in
      experimental design, such as incomplete or inadequate method description, data
      misinterpretation, and reporting may introduce bias and give false-positive
      results. Thus, scientific publications should follow strict guidelines that
      include randomization, blinding, sample-size estimation, and accurate handling of
      all data (Landis et al., 2012). A prolonged state of inflammation after brain
      injury may linger for years and predispose patients to develop other neurological
      disorders, such as Alzheimer's disease. TBI patients display progressive and long
      lasting impairments in their physical, cognitive, behavioral, and social
      performance. Here, we discuss inflammatory mechanisms that accompany TBI in an
      effort to increase our understanding of the dynamic pathological condition as the
      disease evolves over time and begin to translate these findings for defining new
      and existing inflammation-based biomarkers and treatments for TBI.

PMID- 23531683
TI  - Endogenous estrogen and androgen levels are not independent predictors of lipid
      levels in postmenopausal women.
AB  - OBJECTIVE: The relationships between endogenous sex hormone levels and
      cardiovascular disease risk in women are contentious. Our aim was to
      systematically investigate the relationships between sex steroids and lipid
      levels in postmenopausal women, taking into account other potential risk factors.
      METHODS: This is a cross-sectional study of 624 naturally and surgically
      postmenopausal women not using any systemic hormones or lipid-lowering therapy,
      with a mean (SD) age of 53.9 (5.8) years, who were recruited in the United
      States, Canada, Australia, UK, and Sweden between July 2004 and February 2005.
      The relationships between total testosterone, dihydrotestosterone, estrone,
      estradiol, sex hormone-binding globulin (SHBG), the homeostasis model assessment
      for insulin resistance (HOMA-IR), and each lipid variable were explored using
      multivariable linear regression. RESULTS: None of the sex steroids measured made
      an independent contribution to the multivariable models for total cholesterol,
      high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL)
      cholesterol, non-HDL cholesterol, or triglycerides (TG). The best model for total
      cholesterol included race and age, and that for LDL cholesterol included race and
      blood pressure, with each model only explaining 4.8% and 3.3% of the variation in
      each lipid, respectively. About 7.7% of the variation in non-HDL cholesterol was
      explained by HOMA-IR, race, and SHBG. HOMA-IR, SHBG, age, and surgical menopause
      explained 22.8% of the variation in HDL cholesterol, whereas HOMA-IR, SHBG, race,
      and surgical menopause explained 25.4% of the variation in TG. CONCLUSIONS:
      Endogenous estrogen and androgen levels are not independent predictors of lipid
      levels in postmenopausal women. HOMA-IR and SHBG each make independent
      contributions to HDL cholesterol and TG. These factors make little contribution
      to total and LDL cholesterol.

PMID- 23531684
TI  - Human immunodeficiency virus and menopause.
AB  - OBJECTIVE: This article aims to review currently available evidence for women
      infected with human immunodeficiency virus (HIV) and menopause and to propose
      clinical management algorithms. METHODS: Key studies addressing HIV and menopause
      have been reviewed, specifically age of menopause onset in HIV-infected women,
      frequency of menopausal symptoms, comorbidities associated with HIV and aging
      (including cardiovascular disease and bone disease), treatment of menopausal
      symptoms, and prevention of comorbidities in HIV-infected women. RESULTS: Studies
      suggest an earlier onset of menopause in HIV-infected women, with increased
      frequency of symptoms. Cardiovascular disease risk may be increased in this
      population, with combination antiretroviral therapy (cART) and chronic
      inflammation associated with HIV, contributing to increased risk. Chronic
      inflammation and cART have been independently implicated in bone disease. No
      published data have assessed the safety and efficacy of hormone therapy in
      relation to symptoms of menopause, cardiovascular risk, and bone disease among
      HIV-infected women. CONCLUSIONS: Few studies on menopause have been conducted in
      HIV-infected women compared with HIV-uninfected women. Many questions regarding
      age of menopause onset, frequency of menopausal symptoms and associated
      complications such as bone disease and cardiovascular disease, and efficacy of
      treatment among HIV-infected women remain. The incidence and severity of some of
      these factors may be increased in the setting of HIV and cART.

PMID- 23531685
TI  - Relationship between sympathetic nerve activity and aortic wave reflection
      characteristics in postmenopausal women.
AB  - OBJECTIVE: Aortic wave reflection characteristics, such as augmentation index,
      are positively related to muscle sympathetic nerve activity in young men. In
      young women, there is an inverse relationship. We investigated whether this
      inverse relationship persisted in postmenopausal women. METHODS: Muscle
      sympathetic nerve activity (peroneal microneurography) and arterial pressure
      (brachial catheter) were measured in 16 postmenopausal women (mean [SEM] age, 60
      [2] y). Aortic blood pressure and wave form characteristics were synthesized from
      radial arterial pressure waves (applanation tonometry). Specifically,
      augmentation index, wave reflection amplitude, and estimated wasted left
      ventricular energy were calculated. These data were compared with our previously
      published work from an identical protocol in 23 young women (mean [SEM] age, 25
      [1] y). RESULTS: Tonic sympathetic activity was higher in postmenopausal women
      than in young women (64 [3] vs 24 [4] bursts/100 heartbeats). All indices of
      aortic wave reflection were higher in postmenopausal women than in young women (P
      < 0.05). Baseline sympathetic activity was inversely related to augmentation
      index (r = -0.63, P < 0.05), augmented pressure (r = -0.62, P < 0.05), and wasted
      left ventricular energy (r = -0.61, P < 0.05) in young women. Conversely,
      baseline sympathetic activity was positively related to augmentation index (r =
      0.63, P = 0.09), augmented pressure (r = 0.69, P < 0.05), and wasted left
      ventricular energy (r = 0.79, P < 0.05) in postmenopausal women. CONCLUSIONS:
      High levels of sympathetic activity are associated with higher indices of aortic
      wave reflection in postmenopausal women. Consequently, postmenopausal women with
      high sympathetic activity may be more at risk for developing cardiovascular
      diseases or experiencing adverse cardiovascular system-related events.

PMID- 23531686
TI  - Physical activity and sleep among midlife women with vasomotor symptoms.
AB  - OBJECTIVE: Few studies have examined the relationship between physical activity
      and sleep among women with vasomotor symptoms. We examined the associations of
      habitual leisure time and household physical activity with sleep characteristics
      among women reporting vasomotor symptoms. METHODS: A subcohort of women (N = 52:
      white, 27; African American, 25) in the Study of Women's Health Across the Nation
      was assessed for self-reported and actigraphic sleep measurements for four
      nights. Women were between 54 and 63 years, were currently experiencing vasomotor
      symptoms, and were not taking selective serotonin reuptake inhibitors or hormone
      therapy. The associations between physical activity (leisure time and household)
      and sleep (diary, actigraphy, and global sleep quality), as well as interactions
      by race and body mass index, were assessed using logistic regression and
      generalized estimating equations. RESULTS: Greater leisure time physical activity
      was associated with higher odds of rating global sleep quality as good (OR, 8.08,
      95% CI, 1.5, 44.5, P = 0.02). Greater household physical activity was associated
      with more favorable diary-reported sleep characteristics, including fewer
      awakenings during the night (B = -0.14, SE = 0.06, P = 0.01). Exploratory
      analyses suggest that household physical activity was associated with more
      favorable sleep characteristics primarily among white and nonobese women.
      CONCLUSIONS: Greater levels of habitual physical activity, particularly non
      leisure time physical activity, are associated with more favorable sleep
      characteristics. Considering the potential impact of physical activity on sleep,
      even at the relatively modest levels characteristic of household physical
      activity, may be important for women with vasomotor symptoms, a subgroup at high
      risk for sleep problems.

PMID- 23531687
TI  - Consequences of incontinence for women during the menopausal transition and early
      postmenopause: observations from the Seattle Midlife Women's Health Study.
AB  - OBJECTIVE: Although urinary incontinence becomes more prevalent as women age,
      little is known about the outcomes of urinary incontinence in midlife women. Our
      aim was to determine the effects of urinary incontinence (stress and urge) on
      mood (depressed mood, anxiety), perceptions of self (self-esteem, mastery,
      perceived health), attitudes toward midlife (attitudes toward aging, attitudes
      toward menopause), and consequences for daily living (interference with
      relationships, interference with work, sexual desire, physical activity,
      awakening at night, social support, stress), taking into account the effects of
      aging METHODS: A subset of Seattle Midlife Women's Health Study participants (n =
      299, with up to 2,206 observations) provided data during the late reproductive
      stage, early menopausal transition, late menopausal transition, and early
      postmenopause, including menstrual calendars, annual health questionnaire since
      1990, and symptom diaries. Multilevel modeling (R program) was used to test
      models accounting for urinary incontinence outcomes. RESULTS: Stress urinary
      incontinence and urge urinary incontinence were significantly associated with
      lower self-esteem (P = 0.01 and P = 0.001, respectively) and mastery (P < 0.001,
      stress urinary incontinence and urge urinary incontinence), with age included in
      the models as a measure of time. Urinary incontinence's effects on mood symptoms,
      attitudes toward aging, attitudes toward menopause, perceived health, and
      consequences for daily living were not significant (P > 0.05). CONCLUSIONS:
      Urinary incontinence during the menopausal transition and early postmenopause
      seems to affect perceptions of self--but not mood, attitudes toward midlife, or
      consequences for daily living--in this midlife population. Appropriate therapies
      for urinary incontinence during midlife may promote higher levels of self-esteem
      and a greater sense of mastery by older women.

PMID- 23531688
TI  - Risk factors for night sweats and hot flushes in midlife: results from a
      prospective cohort study.
AB  - OBJECTIVE: This study aims to identify social, lifestyle, and reproductive
      history risk factors for night sweats (NS) only, hot flushes (HF) only, and both
      NS and HF. METHODS: Risk factors and symptoms among 10,454 participants of the
      Australian Longitudinal Study on Women's Health who were aged 45 to 50 years in
      1996 were measured at baseline and 3-year intervals (surveys 2-6) for 15 years.
      Multinomial logistic regression analyses were performed. RESULTS: Compared with
      neither symptom, both symptoms together were reported less often by highly
      educated women (odds ratio, 0.61; 99.9% CI, 0.50-0.74), but more often by women
      who were heavier (odds ratio, 1.23; 99.9% CI, 1.08-1.40), were current smokers
      (odds ratio, 1.31; 99.9% CI, 1.09-1.56), were high-risk drinkers (odds ratio,
      1.44; 99.9% CI, 1.10-1.89), were perimenopausal (odds ratio, 6.57; 99.9% CI, 5.52
      7.82) or postmenopausal (odds ratio, 4.74; 99.9% CI, 4.00-5.63), had gained
      weight (odds ratio, 1.15; 99.9% CI, 1.01-1.31), or had premenstrual tension (odds
      ratio, 1.86; 99.9% CI, 1.48-2.34), than by women without these characteristics.
      HF only was reported less often by highly educated women (odds ratio, 0.73; 99.9%
      CI, 0.59-0.90), but more often by perimenopausal (odds ratio, 3.58; 99.9% CI,
      2.95-4.35) or postmenopausal (odds ratio, 2.97; 99.9% CI, 2.47-3.57) women and by
      those with premenstrual tension (odds ratio, 1.60; 99.9% CI, 1.25-2.04). Finally,
      NS only was reported more often among current smokers (odds ratio, 1.55; 99.9%
      CI, 1.11-2.19), high-risk drinkers (odds ratio, 1.76; 99.9% CI, 1.04-2.97),
      perimenopausal women (odds ratio, 1.53; 99.9% CI, 1.14-2.06), those with diabetes
      (odds ratio, 1.91; 99.9% CI, 1.08-3.35), those with premenstrual tension (odds
      ratio, 1.67; 99.9% CI, 1.09-2.56), or those of early age at first pregnancy (odds
      ratio, 1.45; 99.9% CI, 1.05-1.99). CONCLUSIONS: The presence of both symptoms is
      associated with social, behavioral, and menstrual factors. Some differences in
      risk factors among women who report only one symptom or both symptoms are
      observed, suggesting a slightly different etiology for each.

PMID- 23531689
TI  - High-intensity aquatic exercises (HydrOS) improve physical function and reduce
      falls among postmenopausal women.
AB  - OBJECTIVE: This study aims to investigate the effects of an aquatic exercise
      program (HydrOS) on neuromuscular function and falls among postmenopausal women.
      METHODS: One hundred eight postmenopausal women (mean [SD] age, 58.8 [6.4] y)
      were randomly divided into the control group (CG; n = 44) and the aquatic
      exercise group (AEG; n = 64). Both groups received elementary calcium 500 mg/day
      and cholecalciferol 1,000 IU/day. For 24 weeks, the AEG participated in the
      aquatic exercise program, whereas the CG remained sedentary. The following
      variables were measured before and after the program: number of falls and fallers
      (7 mo before and after the intervention); flexibility, using Wells' Sit-and-Reach
      Test (FLEX); static balance, using the Unipedal Stance Test (UST); mobility,
      using the Timed-Up-and-Go test (TUG); handgrip strength of the dominant hand
      (HGS); and maximal isometric strength of back extensor muscles (SBE), strength of
      hip flexor muscles (SHF), and strength of knee extensor muscles (SKE). The muscle
      strength tests were considered the primary outcome, whereas the other
      neuromuscular tests, together with falls, were considered secondary outcomes.
      Results were significant when P <= 0.05. RESULTS: Serum 25-hydroxyvitamin D
      significantly increased by 21% in the CG and by 23% in the AEG (P < 0.001). The
      number of falls and fallers after the program remained unchanged in the CG; in
      the AEG, the mean number of falls decreased from 2.00 to 0.29 (P < 0.0001), and
      the number of fallers decreased by 44% (P < 0.0001). All neuromuscular variables
      significantly improved in the AEG: FLEX (26.6%; P < 0.0001), UST (14.1%; P <
      0.001), TUG (23.7%; P < 0.001), HGS (13.4%; P < 0.001), SBE (26.2%; P < 0.001),
      SHF (18.5%; P = 0.039), and SKE (7.7%; P < 0.001). In the CG, significant
      improvements in FLEX (12.2%; P = 0.009), UST (4.5%; P < 0.001), TUG (10%; P <
      0.001), and SHF (5.7%; P = 0.039) were observed and could be explained by
      increasing serum 25-hydroxyvitamin D level attributable to supplementation.
      CONCLUSIONS: The aquatic exercise program HydrOS is a safe and efficient way to
      improve physical function and to reduce falls among postmenopausal women.

PMID- 23531690
TI  - S6K1 and E2FB are in mutually antagonistic regulatory links controlling cell
      growth and proliferation in Arabidopsis.
AB  - Plant development is dependent on the coordination between growth and cell
      proliferation. The nutrient sensing TOR kinase and its downstream target, the 40S
      ribosomal S6 Kinase, are central controllers of cell growth that were also shown
      to determine cell size by inhibiting the onset of mitosis in yeast and animal
      cells. We have shown that the Arabidopsis S6 Kinase1 inhibits cell proliferation
      through the RBR-E2FB complex. S6K1 interacts with RBR via its N-terminal RBR
      binding motif, promotes its nuclear localization and consequent RBR-dependent
      repression of cell cycle genes through E2FB. Here we show that S6K1 and E2FB are
      in a mutually antagonistic relationship both in their protein abundance and in
      their activity. We propose that this double inhibitory regulatory connection
      between S6K1 and E2FB forms a regulatory switch that might be important to
      determine whether cells divide or grow. 

PMID- 23531691
TI  - "What we've got here is failure to communicate": zou mutants and endosperm cell
      death in seed development.
AB  - ZHOUPI, a unique and highly conserved bHLH transcription factor, controls both
      endosperm breakdown and embryonic surface formation during Arabidopsis seed
      development. We have demonstrated that these two processes are distinct, and that
      ZHOUPI regulates embryonic surface formation via a signaling pathway mediated by
      the subtilisin-like serine protease ABNORMAL LEAF SHAPE1, and the receptor
      kinases GASSHO1 and GASSHO2. Gene expression profiling in mutant backgrounds has
      permitted the identification of genes whose expression depends on both ZHOUPI and
      ABNORMAL LEAF SHAPE1 and genes whose expression depends uniquely on ZHOUPI. The
      latter are presumably involved specifically in endosperm breakdown, and we
      discuss this poorly understood process in the light of our results. Finally, we
      consider the potential ancestral role of ZHOUPI and discuss how its relationship
      with ABNORMAL LEAF SHAPE1 may have evolved. 

PMID- 23531692
TI  - The emerging function of IQD proteins as scaffolds in cellular signaling and
      trafficking.
AB  - Calcium (Ca(2+)) signaling modules are essential for adjusting plant growth and
      performance to environmental constraints. Differential interactions between
      sensors of Ca(2+) dynamics and their molecular targets are at the center of the
      transduction process. Calmodulin (CaM) and CaM-like (CML) proteins are principal
      Ca(2+)-sensors in plants that govern the activities of numerous downstream
      proteins with regulatory properties. The families of IQ67-Domain (IQD) proteins
      are a large class of plant-specific CaM/CML-targets (e.g., 33 members in A.
      thaliana) which share a unique domain of multiple varied CaM retention motifs in
      tandem orientation. Genetic studies in Arabidopsis and tomato revealed first
      roles for IQD proteins related to basal defense response and plant development.
      Molecular, biochemical and histochemical analysis of Arabidopsis IQD1
      demonstrated association with microtubules as well as targeting to the cell
      nucleus and nucleolus. In vivo binding to CaM and kinesin light chain-related
      protein-1 (KLCR1) suggests a Ca(2+)-regulated scaffolding function of IQD1 in
      kinesin motor-dependent transport of multiprotein complexes. Furthermore, because
      IQD1 interacts in vitro with single-stranded nucleic acids, the prospect arises
      that IQD1 and other IQD family members facilitate cellular RNA localization as
      one mechanism to control and fine-tune gene expression and protein sorting.

PMID- 23531693
TI  - A PHD in histone language: on the role of histone methylation in plant responses
      to phosphate deficiency.
AB  - Post-translational modifications of core histones are important for various DNA
      templated processes such as transcription and repair. We recently reported that
      the ALFIN LIKE 6 (AL6) gene, identified in a forward genetic screen, is critical
      for phosphate deficiency-induced root hair formation and several other processes
      associated with the regulation of cellular phosphate homeostasis. AL6 contains a
      Plant Homeo Domain (PHD) finger that can bind to trimethylated lysine 4 of
      histone H3 (H3K4me3). Homozygous mutants defective in AL6 expression form very
      short root hairs under phosphate-deficient conditions, presumably caused by
      altered expression of putative primary and secondary down-stream targets of AL6.
      In this Addendum, we speculate about possible roles of AL6, H3K4 trimethylation
      and other chromatin modifications in the adaptation of plants to low phosphate
      availability. 

PMID- 23531694
TI  - Interactive regulation of nitrogen and aluminum in rice.
AB  - Despite many studies on the high aluminum (Al) tolerance of rice (Oryza sativa),
      its exact mechanisms remain largely unknown. It is also unclear why Al improves
      growth of some plants. Our research on interactions between nitrogen (N) and Al
      may help to understand these phenomena. Previously, we found that ammonium
      supplemented rice was more Al tolerant than nitrate-supplemented rice.
      Furthermore, Al-tolerant rice varieties preferred ammonium, while Al-sensitive
      ones preferred nitrate; in fact, Al tolerance was significantly correlated with
      the ammonium/nitrate preference among rice varieties. Al even enhanced growth of
      ammonium-supplemented rice, while it inhibited growth of nitrate-supplemented
      rice. Based on our own and other reports on N-Al interactions, we propose that
      intermediate products of N metabolism may play a role in rice Al tolerance. Al
      enhanced ammonium utilization may explain why Al promotes growth of some plants,
      since Al often coexists with higher levels of ammonium than nitrate in acid
      soils. 

PMID- 23531695
TI  - Cancer stem cell and stromal microenvironment.
AB  - BACKGROUND: Chemotherapeutic resistance and local recurrence or distant organ
      metastasis are the major causes of cancer mortality. Conventional cancer
      treatments do not consistently prevent cancer recurrence. METHODS: We illustrate
      the key roles that cancer stem cells and the tumor microenvironment-particularly
      the lymph node stromal microenvironment-play in tumor drug resistance,
      metastasis, and recurrence in 2 representative cancers: colorectal cancer and
      follicular lymphoma. CONCLUSION: We believe that combination treatment with
      chemotherapeutic agents in conjunction with targeted therapies, such as
      stromal/cancer stem cell signaling-targeted therapy, may effectively minimize
      cancer recurrence.

PMID- 23531696
TI  - Plasticity: the benefits of a novel environment.

PMID- 23531698
TI  - Addiction: craving: a core issue.

PMID- 23531699
TI  - Steroid sulphatase and oestrogen sulphotransferase in human non-small-cell lung
      carcinoma.
AB  - BACKGROUND: Steroid sulphatase (STS) is one of the steroid-metabolising enzymes
      involved in desulphating inactive steroid sulphates and oestrogen
      sulphotransferase (EST) sulphates active oestrogen. The roles of both STS and EST
      have not been examined in oestrogen-dependent non-small-cell lung cancer (NSCLC).
      METHODS: We evaluated the immunoreactivity of STS and EST in NSCLC cases using
      immunohistochemistry. The function of STS and EST was further demonstrated using
      NSCLC cell lines. RESULTS: The immunoreactivity of STS and EST was detected in
      49.5% and 27.8% of NSCLC cases, respectively. The immunoreactivity of STS was
      significantly higher in female adenocarcinoma cases. The STS-positive NSCLCs were
      also significantly correlated in an inversed manner with tumour size and cell
      proliferation and tended to be associated with better clinical outcome. However,
      the immunoreactivity of EST was significantly correlated with intracellular
      oestradiol concentration. Results of in vitro analysis demonstrated that oestrone
      sulphate (E1-S) induced and pregnenolone sulphate (Preg-S) inhibited the
      proliferation in STS-expressing cell lines. The inhibition by Preg-S was reversed
      by a specific progesterone receptor blocker. Simultaneous addition of E1-S and
      Preg-S significantly suppressed the proliferation. CONCLUSION: In NSCLC patients,
      STS is considered a good prognostic factor. Results of our present study also
      indicated the benefits of potential progesterone therapy for NSCLC patients.

PMID- 23531700
TI  - Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and
      increases sensitivity to bortezomib.
AB  - BACKGROUND: Dichloroacetate (DCA), through the inhibition of aerobic glycolysis
      (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth
      reduction in many tumours and is now undergoing several clinical trials. If
      aerobic glycolysis is active in multiple myeloma (MM) cells, it can be
      potentially targeted by DCA to induce myeloma growth inhibition. METHODS:
      Representative multiple myeloma cell lines and a myeloma-bearing mice were
      treated with DCA, alone and in combination with bortezomib. RESULTS: We found
      that aerobic glycolysis occurs in approximately half of MM cell lines examined,
      producing on average 1.86-fold more lactate than phorbol myristate acetate
      stimulated-peripheral blood mononuclear cells and is associated with low
      oxidative capacity. Lower doses of DCA (5-10 mM) suppressed aerobic glycolysis
      and improved cellular respiration that was associated with activation of the
      pyruvate dehydrogenase complex. Higher doses of DCA (10-25 mM) induced superoxide
      production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest
      in MM cell lines. In addition, DCA increased MM cell line sensitivity to
      bortezomib, and combinatorial treatment of both agents improved the survival of
      myeloma-bearing mice. CONCLUSION: Myeloma cells display aerobic glycolysis and
      DCA may complement clinically used MM therapies to inhibit disease progression.

PMID- 23531697
TI  - Imaging structural co-variance between human brain regions.
AB  - Brain structure varies between people in a markedly organized fashion.
      Communities of brain regions co-vary in their morphological properties. For
      example, cortical thickness in one region influences the thickness of
      structurally and functionally connected regions. Such networks of structural co
      variance partially recapitulate the functional networks of healthy individuals
      and the foci of grey matter loss in neurodegenerative disease. This architecture
      is genetically heritable, is associated with behavioural and cognitive abilities
      and is changed systematically across the lifespan. The biological meaning of this
      structural co-variance remains controversial, but it appears to reflect
      developmental coordination or synchronized maturation between areas of the brain.
      This Review discusses the state of current research into brain structural co
      variance, its underlying mechanisms and its potential value in the understanding
      of various neurological and psychiatric conditions.

PMID- 23531701
TI  - Treatment and overall survival in renal cell carcinoma: a Swedish population
      based study (2000-2008).
AB  - BACKGROUND: This retrospective register study assessed overall survival (OS) and
      influential factors on OS in Swedish renal cell carcinoma (RCC) patients.
      METHODS: Using three merged national health registers, Cox proportional-hazards
      analysis was conducted and, in three models, it was used to assess the impact of
      cytokine (interferon-alpha and tyrosine kinase inhibitor (TKI; sunitinib or
      sorafenib) treatment on OS in metastatic (m)RCC. RESULTS: From 2000 to 2008, 8009
      patients were diagnosed with RCC and 2753 with mRCC (2002-2008). Median OS in RCC
      patients diagnosed from 2006 to 2008 compared with 2000-2005 was not reached vs
      47.9 months (P<0.001), and in mRCC patients diagnosed from 2006 to 2008 compared
      with 2002-2005, was 12.4 vs 9.6 months, respectively (P=0.004). Factors
      associated with significantly improved OS in RCC were female gender, lower age,
      and previous nephrectomy, and, in mRCC female gender, previous nephrectomy, and
      any TKI prescription (Model 1: median-adjusted OS, 19.4 months (TKI patients) vs
      9.7 months (non-TKI patients); hazard ratio, 0.621; P<0.001). CONCLUSION: OS was
      improved in Swedish patients diagnosed with RCC and mRCC in the period 2006-2008
      compared with 2000-2005 (RCC) and 2002-2005 (mRCC). Although multifactorial in
      origin, results suggest that increased nephrectomy rates and the use of TKIs
      contributed to the improvement seen in mRCC patients.

PMID- 23531702
TI  - Biometals in rare neurodegenerative disorders of childhood.
AB  - Copper, iron, and zinc are just three of the main biometals critical for correct
      functioning of the central nervous system (CNS). They have diverse roles in many
      functional processes including but not limited to enzyme catalysis, protein
      stabilization, and energy production. The range of metal concentrations within
      the body is tightly regulated and when the balance is perturbed, debilitating
      effects ensue. Homeostasis of brain biometals is mainly controlled by various
      metal transporters and metal sequestering proteins. The biological roles of
      biometals are vastly reviewed in the literature with a large focus on the
      connection to neurological conditions associated with ageing. Biometals are also
      implicated in a variety of debilitating inherited childhood disorders, some of
      which arise soon following birth or as the child progresses into early adulthood.
      This review acts to highlight what we know about biometals in childhood
      neurological disorders such as Wilson's disease (WD), Menkes disease (MD),
      neuronal ceroid lipofuscinoses (NCLs), and neurodegeneration with brain iron
      accumulation (NBIA). Also discussed are some of the animal models available to
      determine the pathological mechanisms in these childhood disorders, which we hope
      will aid in our understanding of the role of biometals in disease and in
      attaining possible therapeutics in the future.

PMID- 23531703
TI  - Meta-analysis reveals evolution in invasive plant species but little support for
      Evolution of Increased Competitive Ability (EICA).
AB  - Ecological explanations for the success and persistence of invasive species
      vastly outnumber evolutionary hypotheses, yet evolution is a fundamental process
      in the success of any species. The Evolution of Increased Competitive Ability
      (EICA) hypothesis (Blossey and Notzold 1995) proposes that evolutionary change in
      response to release from coevolved herbivores is responsible for the success of
      many invasive plant species. Studies that evaluate this hypothesis have used
      different approaches to test whether invasive populations allocate fewer
      resources to defense and more to growth and competitive ability than do source
      populations, with mixed results. We conducted a meta-analysis of experimental
      tests of evolutionary change in the context of EICA. In contrast to previous
      reviews, there was no support across invasive species for EICA's predictions
      regarding defense or competitive ability, although invasive populations were more
      productive than conspecific native populations under noncompetitive conditions.
      We found broad support for genetically based changes in defense and competitive
      plant traits after introduction into new ranges, but not in the manner suggested
      by EICA. This review suggests that evolution occurs as a result of plant
      introduction and population expansion in invasive plant species, and may
      contribute to the invasiveness and persistence of some introduced species.

PMID- 23531704
TI  - A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the
      Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes.
AB  - Given that buprenorphine + naloxone is prescribed for opioid-dependent pregnant
      women, it is important to examine the extent to which it differs from
      buprenorphine alone, methadone, or methadone-assisted withdrawal on neonatal and
      maternal outcomes. Summary statistics on maternal and neonatal outcomes were
      collected from 7 previously published studies examining treatment for opioid
      dependent pregnant women that represented a range of research methodologies.
      Outcomes from these studies were compared to the same outcomes for 10 women
      treated with the combined buprenorphine + naloxone product. There were no
      significant differences in maternal outcomes for buprenorphine + naloxone
      compared to buprenorphine, methadone, or methadone-assisted withdrawal.
      Preliminary findings suggest no significant adverse maternal or neonatal outcomes
      related to the use of buprenorphine + naloxone for the treatment of opioid
      dependence during pregnancy. However, further research should examine possible
      differences between buprenorphine + naloxone and buprenorphine alone or methadone
      in fetal physical development.

PMID- 23531705
TI  - Clomiphene citrate or letrozole as first-line ovulation induction drug in
      infertile PCOS women: A prospective randomized trial.
AB  - OBJECTIVE: To compare Letrozole (5 mg) and clomiphene citrate (100 mg) as first
      line ovulation induction drug in infertile PCOS women. STUDY DESIGN: Prospective
      Randomised trial. SETTING: A Tertiary level infertility centre. PATIENTS: 103
      infertile PCOS women. INTERVENTIONS: Treatment naive infertile PCOS women were
      randomised to treatment with 5 mg letrozole (51 patients) or 100 mg clomiphene
      citrate (52 patients) daily starting day 2 to day 6 of menstrual cycle. Timed
      intercourse or Intra Uterine Insemination (IUI) was advised 24 to 36 hours after
      Human Chorionic Gonadotropin (HCG) injection. MAIN OUTCOME MEASURES: Ovulation
      rate, mono or multi follicular rate, days to ovulation, endometrial thickness,
      serum progesterone, serum estrogen, pregnancy rate, miscarriage rate. RESULTS:
      The mean age, Body Mass Index (BMI), duration of infertility in both Clomiphene
      Citrate (CC) and Letrozole groups were similar.Ovulation rate was 73.08% in
      letrozole group and 60.78% in CC, which was not statistically significant
      (P=0.398). There was no statistically significant difference between Endometrial
      thickness (CC 7.61 +/-1.96, Let 7.65 +/- 2.10), Sr E2 on day of HCG (CC 178.3 +/-
      94.15, Let 162.09 +/- 73.24), Days to ovulation (CC 14.2 +/- 3.41; Let 13.13 +/-
      2.99) and Sr P4 on D21 (CC 10.58 +/- 6.65; Let 11.86 +/- 6.51). Monofolliculo
      genesis (CC 54.84, Let 79.49 %, P=0.027) and Pregnancy rate (CC 7.84%, Let 21.56%
      P=0.0125) were statistically significantly higher in letrozole group. CONCLUSION:
      Our study shows that letrozole has excellent pregnancy rates compared to
      clomiphene citrate. Letrozole should be considered at par with clomiphene citrate
      as first line drug for ovulation induction in infertile PCOS women.

PMID- 23531706
TI  - Neonatal suppression-burst without epileptic seizures: expanding the
      electroclinical phenotype of STXBP1-related, early-onset encephalopathy.
AB  - Early-onset epileptic encephalopathies (EOEEs) are characterised by epileptic
      seizures beginning in the first months of life, abnormal background EEG activity,
      and are associated with severe developmental delay and poor prognosis. Mutations
      and deletions in the STXBP1 gene are associated with Ohtahara syndrome, also
      known as "early infantile epileptic encephalopathy". We report an infant affected
      by EOEE with a 9q34.11 deletion that encompassed the genes STXBP1 and SPTAN1. The
      infant presented with neonatal encephalopathy without epileptic seizures and an
      EEG pattern varying from highly discontinuous to suppression-burst. This was
      followed by West syndrome at 2 months with atypical hypsarrhythmia and spasms,
      easily controlled by therapy. Our findings suggest that molecular analysis of
      STXBP1 should be considered for newborns affected by neonatal encephalopathy
      associated with a peculiar EEG pattern, even in the absence of neonatal epileptic
      seizures.

PMID- 23531707
TI  - Decompression alone versus decompression with limited fusion for treatment of
      degenerative lumbar scoliosis in the elderly patient.
AB  - STUDY DESIGN:  Retrospective cohort study. OBJECTIVE:  To analyze the surgical
      results of a group of patients older than 65 years treated for mild degenerative
      lumbar scoliosis (<30 degrees ) with stenosis, treated with decompression alone
      or decompression and limited fusion. METHODS:  We evaluated 55 patients, all
      older than 65 years from our prospectively collected database with mild
      degenerative scoliosis (<30 degrees ) and stenosis who underwent surgery.
      Laminectomy alone was performed in 16 patients, and laminectomy and limited
      fusion in 39 patients. Mean follow-up was 4.6 years in the decompression group
      and 5.0 years in the fusion group. Clinical results were graded by patients' self
      reported satisfaction and length of symptom-free period to recurrence. RESULTS: 
      In the decompression alone group, 6 (37%) of 16 patients developed recurrent
      stenosis at the previously decompressed level and five developed recurrence
      within 6 months postoperatively versus the decompression and fusion group where 3
      (8%) of 39 (P = .0476) developed symptomatic stenosis supra adjacent to the
      fusion. Of 16 patients in the decompression alone group, 12 (75%) had recurrence
      of symptoms by the 5-year follow-up period versus only 14 (36%) patients in the
      decompression and fusion group (P = .016). Adjacent segment degenerative changes
      were common in the fusion group, but only 7% developed symptomatic stenosis.
      CONCLUSIONS:  Decompression with limited fusion prevents early return of stenotic
      symptoms compared with decompression alone in the setting of mild degenerative
      scoliosis (<30 degrees ) and symptomatic stenosis in patients 65 years and older.
      [Table: see text] The definiton of the different classes of evidence is available
      on page 67.

PMID- 23531708
TI  - Mutations in PYCR1 gene in three families with autosomal recessive cutis laxa,
      type 2.

PMID- 23531709
TI  - Connectivity in a pond system influences migration and genetic structure in
      threespine stickleback.
AB  - Neutral genetic structure of natural populations is primarily influenced by
      migration (the movement of individuals and, subsequently, their genes) and drift
      (the statistical chance of losing genetic diversity over time). Migration between
      populations is influenced by several factors, including individual behavior,
      physical barriers, and environmental heterogeneity among populations. However,
      drift is expected to be stronger in populations with low immigration rate and
      small effective population size. With the technological advancement in geological
      information systems and spatial analysis tools, landscape genetics now allows the
      development of realistic migration models and increased insight to important
      processes influencing diversity of natural populations. In this study, we
      investigated the relationship between landscape connectivity and genetic distance
      of threespine stickleback (Gasterosteus aculeatus) inhabiting a pond complex in
      Belgjarskogur, Northeast Iceland. We used two landscape genetic approaches (i.e.,
      least-cost-path and isolation-by-resistance) and asked whether gene flow, as
      measured by genetic distance, was more strongly associated with Euclidean
      distance (isolation-by-distance) or with landscape connectivity provided by areas
      prone to flooding (as indicated by Carex sp. cover)? We found substantial genetic
      structure across the study area, with pairwise genetic distances among
      populations (DPS) ranging from 0.118 to 0.488. Genetic distances among
      populations were more strongly correlated with least-cost-path and isolation-by
      resistance than with Euclidean distance, whereas the relative contribution of
      isolation-by-resistance and Euclidian distance could not be disentangled. These
      results indicate that migration among stickleback populations occurs via
      periodically flooded areas. Overall, this study highlights the importance of
      transient landscape elements influencing migration and genetic structure of
      populations at small spatial scales.

PMID- 23531710
TI  - Intraoperative CT navigation for glenoid component fixation in reverse shoulder
      arthroplasty.
AB  - CT navigation has been shown to improve component positioning in total shoulder
      arthroplasty. The technique can be useful in achieving strong initial fixation of
      the metal backed glenoid in reverse shoulder arthroplasty. We report a 61 years
      male patient who underwent reverse shoulder arthroplasty for rotator cuff
      arthropathy. CT navigation was used intraoperatively to identify best possible
      glenoid bone and to maximize the depth of the fixation screws that anchor the
      metaglene portion of the metal backed glenoid component. Satisfactory positioning
      of screws and component was achieved without any perforation or iatrogenic
      fracture in the scapula. CT navigation can help in maximizing the purchase of the
      fixation screws that dictate the initial stability of the glenoid component in
      reverse shoulder arthroplasty. The technique can be extended to improve glenoid
      component position [version and tilt] with the availability of appropriate
      software.

PMID- 23531711
TI  - Management of spinal epidural arteriovenous fistulas: interventional techniques
      and results.
AB  - BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVF) are rare and poorly
      understood clinical entities. MATERIALS AND METHODS: We report a series of five
      (three men, two women) consecutive cases treated at our center to analyze their
      characteristic and treatment strategies in their management. We report a
      successful technique of percutaneous embolization of fistulas in a patient with
      failed previous attempts. RESULTS: All five patients were symptomatic; three
      patients presented with a history of back pain, which progressed to myelopathic
      symptoms, one patient had symptoms of persistent back pain, and one patient had
      intermittent numbness of the left arm and thigh. Of the three patients who had
      myelopathic symptoms, two were successfully treated with transarterial
      embolizations with Onyx copolymer. The third patient who had a prominent epidural
      venous pouch with numerous arterial feeders was embolized percutaneously with a
      flat detector CT guided navigation (XperCT) and real time fluoroscopic monitoring
      of the injected n-butyl cyanoacrylate glue, after previous unsuccessful attempts
      with surgery and arterial embolizations. All three myelopathic treated patients
      had complete angiographic remission of the fistulas and symptoms on follow-up
      (mean 7.2 months). CONCLUSIONS: The diagnosis and treatment of SEDAVF can be
      challenging due to their rarity and intricate pathomechanics. Patients with
      severe pain or progression of symptoms or myelopathic symptoms need to be treated
      at the earliest opportunity, while asymptomatic patients can be closely
      monitored. Percutaneous embolization is an effective strategy to embolize SEDAVF
      associated venous pouch.

PMID- 23531712
TI  - Hydrodynamic comparison of the Penumbra system and commonly available syringes in
      forced-suction thrombectomy.
AB  - BACKGROUND: The Penumbra system uses a coaxial separator and continuous
      extracorporeal suction to remove a clot from a cerebral artery. Forced-suction
      thrombectomy (FST) involves aspirating clots through the same reperfusion
      catheter using only a syringe, decreasing the procedure time and supplies needed.
      OBJECTIVE: To evaluate multiple combinations of catheters and syringes to
      determine the optimal pairing for use in FST. METHODS: Tests were performed using
      both the Penumbra system and syringes to aspirate water through Penumbra 0.041
      inch (041), 4Max, 0.054 inch (054) and 5Max reperfusion catheters and a shuttle
      sheath. Dynamic pressure and flow at the catheter tip were calculated from the
      fill times for each system. Static pressure and force for each aspiration source
      were determined with a vacuum gauge. RESULTS: All syringes provided significantly
      higher dynamic pressure at the catheter tip than the Penumbra system (p<0.001).
      Increasing syringe volume significantly increased static pressure (p<0.001). Both
      flow and aspiration force significantly increased with catheter size (p<0.001).
      Cases are presented to demonstrate the clinical value of the laboratory
      principles. CONCLUSIONS: Maximizing static and dynamic pressure when performing
      FST is achieved by aspirating with a syringe possessing both the largest volume
      and the largest inlet diameter available. Maximizing aspiration force and flow
      rate is achieved by using the largest catheter possible.

PMID- 23531713
TI  - Electrophysiological analysis of the role of novelty in the von Restorff effect.
AB  - Items that are distinctive with respect to their context tend to be recalled
      better than nondistinctive items, a finding known as the von Restorff effect. The
      goal of this study was to elucidate the role of novelty in this effect. In two
      experiments, participants performed a dual task in which they had to study words
      presented visually while to-be ignored sounds were played over earphones. Sounds
      could be either standard or novel, and words could be presented in standard or
      novel font. Sounds were presented either simultaneously with the words
      (Experiment 1) or preceding them (Experiment 2). Electrophysiological correlates
      of novelty processing, the N2b and P3a ERP components, were recorded while the
      words were studied. It was seen that cued recall was better for words presented
      in novel fonts than for words in a standard font (the von Restorff effect). Words
      presented while novel sounds were played were remembered worse (Experiment 1) or
      equally well (Experiment 2) than those combined with standard sounds. Words
      presented in novel fonts elicited enhanced N2b, P3a, P3b, and N400 components;
      however, none of these components were specifically larger for subsequently
      recalled novel-font words. A larger N2b was found for recalled than for
      nonrecalled words, but this effect was not specific for words presented in novel
      font. We hypothesized that if novelty was beneficial for memory processing, the
      N2-P3 complex would be more enhanced for novel words that were later recalled
      than for those not recalled. The data showed otherwise. This suggests that
      novelty processing, as indexed by the N2-P3 novelty components, is not the main
      cause of the von Restorff effect.

PMID- 23531714
TI  - Fat mass localization alters fuel oxidation during exercise in normal weight
      women.
AB  - PURPOSE: Abdominal and lower body fat mass tissues exhibit particular metabolic
      profiles at rest and during exercise. However, data are missing in normal weight
      women during exercise. The purpose of this study was to investigate the effect of
      low (LA/LB) and high (HA/LB) abdominal to lower body (A/LB) fat mass ratio on
      metabolic and hormonal responses during exercise in premenopausal normal weight
      women. METHODS: After preliminary testing (VO2max and body composition
      assessment), substrate oxidation (RER, lipid, and carbohydrate oxidation rates),
      metabolic response (glycerol, free fatty acids, and glucose), and hormonal
      response (insulin, growth hormone, atrial natriuretic peptide, adrenaline, and
      noradrenaline) were determined during exercise (45 min at 65% of VO2max) in 21
      premenopausal normal weight women (10 HA/LB women vs 11 LA/LB women). RESULTS:
      Waist circumference was significantly higher in HA/LB women compared with LA/LB
      women (P < 0.01). No difference in other anthropometric characteristics, VO2max,
      and resting blood values was observed between the two groups. LA/LB subjects
      exhibited greater lipid oxidation rates compared with HA/LB women during exercise
      (P < 0.01). This occurred with lower plasma insulin (P < 0.05) and glucose (P <
      0.05) concentrations and higher plasma free fatty acids (P < 0.05), glycerol (P <
      0.05), growth hormone (P < 0.05), and atrial natriuretic peptide levels (P <
      0.01) during exercise in the LA/LB group compared with the HA/LB group.
      CONCLUSIONS: The present study demonstrated that LA/LB women exhibited an
      increase in whole-body lipid mobilization and use during exercise compared with
      HA/LB counterparts. This greater reliance on lipid as fuel metabolism during
      exercise could be explained by substrate availability and metabolic and hormonal
      responses. It appeared that LA/LB women exhibited greater metabolic flexibility
      during an exercise bout of 45 min at 65% of VO2max on cycle ergometer.

PMID- 23531715
TI  - Effect of two doses of interval training on maximal fat oxidation in sedentary
      women.
AB  - INTRODUCTION: The primary aim of the current study was to determine the effect of
      two doses of chronic high-intensity interval training (HIT) on changes in maximal
      fat oxidation (MFO) and body composition. METHODS: Sedentary women (N = 23, age
      and VO2max = 24.2 +/- 6.2 yr and 30.3 +/- 5.2 mL.kg-1.min-1, respectively)
      completed either high (HI) (80%-90% maximal workload) or moderate (MOD) intensity
      (60%-80% maximal workload) HIT on a cycle ergometer 3 d.wk-1 for 12 wk consisting
      of 6-10 sixty-second bouts interspersed with active recovery. Seven women of
      similar age and fitness level served as controls. Every 3 wk, substrate oxidation
      was assessed during progressive exercise via indirect calorimetry to determine
      MFO and minimum fat oxidation, and body composition was assessed every 6 wk.
      Repeated-measures ANOVA was used to examine changes in substrate oxidation in
      response to training, with training group used as a between-subjects variable.
      RESULTS: Results revealed improved MFO (P = 0.04, 19%-25%) and minimum fat
      oxidation (P = 0.001, 22-24 W) in response to HIT, yet the magnitude of
      improvement was similar (P > 0.05) between training paradigms. No change (P >
      0.05) in body weight, percent body fat, or waist-hip circumference was revealed
      with training. CONCLUSION: These data suggest that 12 wk of either moderate or
      more strenuous interval training similarly enhance fat oxidation in sedentary
      women but do not alter body weight or body composition.

PMID- 23531716
TI  - Assessing the contribution of parks to physical activity using global positioning
      system and accelerometry.
AB  - PURPOSE: Parks offer a free option for physical activity in many communities. How
      much time people spend using parks and the contribution that parks makes to their
      physical activity is not known. This study describes patterns of park use and
      physical activity among a diverse adult sample. METHODS: From five US states, 248
      adults enrolled in or near 31 study parks. Participants wore a global positioning
      system (GPS) monitor (Qstarz BT-Q1000X) and an ActiGraph accelerometer (GT1M)
      concurrently for 3 wk. Parks were mapped from local and national park shape
      files. Park visits and travel to and from the parks were derived from the
      objective data. RESULTS: Participants visited parks a median of 2.3 times per
      week, and park visits lasted a median of 42.0 min. Overall, participants engaged
      in a median of 21.7 min.d-1 of moderate activity and 0.1 min.d-1 of vigorous
      activity, with an average of 8.2% of all moderate and 9.4% of all vigorous
      activity occurring within the parks. Among those with at least one park visit (n
      = 218), counts per minute, moderate, moderate-to-vigorous physical activity
      (MVPA), number and time in MVPA bouts per day, and sedentary behavior were all
      higher on days when a park was visited compared with days when a park was not
      visited. Considering several definitions of active travel, walking or bicycling
      to and from the park added an additional 3.7-6.6 mean minutes of MVPA per park
      visit. CONCLUSIONS: Parks contributed as a place and destination for physical
      activity but were underused. One of the next steps in this line of inquiry is to
      understand characteristics of parks used more often as a place and destination
      for physical activity.

PMID- 23531717
TI  - A 26-year follow-up study of heavy drinking trajectories from adolescence to mid
      adulthood and adult disadvantage.
AB  - AIMS: The aim of the study was to identify heavy drinking trajectories from age
      16 to 42 years and to examine their associations with health, social, employment
      and economic disadvantage in mid-adulthood. METHODS: Finnish cohort study's
      participants who were 16 years old in 1983 were followed up at age 22, 32 and 42
      (n = 1334). Heavy drinking was assessed at every study phase and based on these
      measurements trajectories of heavy drinking were identified. The trajectory
      groups were then examined as predictors of disadvantage at age 42. RESULTS: Five
      distinct heavy drinking trajectories were identified: moderate (35%), steady low
      (22%), decreasing (9%), increasing (11%) and steady high (23%). Frequencies of
      the trajectory groups differed by gender. Using the moderate trajectory as a
      reference category, women in the steady high trajectory had an increased risk of
      experiencing almost all disadvantages at age 42. In men, increasing and steady
      high groups had an increased risk for experiencing health and economic
      disadvantage. CONCLUSION: Steady high female drinkers and steady high and
      increasing male drinkers had the highest risk for disadvantage in mid-adulthood.
      By identifying heavy drinking trajectories from adolescence to mid-adulthood we
      can better predict long-term consequences of heavy alcohol use and plan
      prevention and intervention programmes.

PMID- 23531718
TI  - Reduction of drinking in problem drinkers and all-cause mortality.
AB  - Alcohol consumption has been linked with considerable mortality, and reduction of
      drinking, especially of heavy drinking, has been suggested as one of the main
      measures to reduce alcohol-attributable mortality. Aggregate-level studies
      including but not limited to natural experiments support this suggestion;
      however, causality cannot be established in ecological analysis. The results of
      individual-level cohort studies are ambiguous. On the other hand, randomized
      clinical trials with problem drinkers show that brief interventions leading to a
      reduction of average drinking also led to a reduction of all-cause mortality
      within 1 year. The results of these studies were pooled and a model for reduction
      of drinking in heavy drinkers and its consequences for all-cause mortality risk
      was estimated. Ceteris paribus, the higher the level of drinking, the stronger
      the effects of a given reduction. Implications for interventions and public
      health are discussed.

PMID- 23531719
TI  - Intergenerational transmission of drinking motives and how they relate to young
      adults' alcohol use.
AB  - AIMS: This study examined whether parental drinking motives are associated with
      young adults' drinking motives, and their association with young adults' drinking
      behaviors. METHODS: The sample consisted of 290 18-year-old and 289 20-year-old
      drinking young adults and their parents. RESULTS: For the younger group, stronger
      maternal coping motives were related to stronger social and enhancement motives,
      while stronger paternal coping motives were associated with stronger young adult
      coping motives. For the older group, stronger maternal coping motives were
      related to stronger social motives and stronger paternal enhancement motives were
      associated with stronger overall young adult drinking motives. For the younger
      group, both enhancement and conformity motives were predictive of their alcohol
      use. For the older group, only higher social motives were predictive of higher
      alcohol use. Both groups' higher coping and enhancement motives were associated
      with more drinking problems. CONCLUSIONS: While, concerning content, there are
      some differences due to parent gender and adolescent age, stronger parental
      drinking motives are indeed associated with stronger adolescent drinking motives,
      which in turn are quite consistently related to more adolescent alcohol use and
      alcohol-related problems.

PMID- 23531724
TI  - Systems approaches in risk assessment.
AB  - Adverse drug events (ADEs) remain a universal problem in drug development,
      regulatory review, and clinical practice with a substantial financial burden on
      the global health-care system. Recent advances in molecular and "omics"
      technologies, along with online databases and bioinformatics, have enabled a more
      integrative approach to understanding drug-target (protein) interactions, both
      desirable and undesirable, within a biological system. This has led to the
      development of systems approaches to risk assessment in an attempt to complement
      and improve on contemporary observational and predictive strategies for assessing
      risk. Although still in an evolutionary phase, systems approaches have the
      potential to markedly advance our understanding of ADEs and ability to predict
      them. Systems approaches will also move personalized medicine forward by enabling
      better identification of individual and subgroup risk factors.

PMID- 23531725
TI  - Differential genomic variation between short- and long-term bacterial evolution
      revealed by ultradeep sequencing.
AB  - Mutation and selection are both thought to impact significantly the nucleotide
      composition of bacterial genomes. Earlier studies have compared closely related
      strains to obtain mutation patterns based on the hypothesis that these bacterial
      strains had diverged so recently that selection will not have had enough time to
      play its role. In this study, we used a SOLiD autosequencer that was based on a
      dual-base encoding scheme to sequence the genome of Staphylococcus aureus with a
      mapping coverage of over 5,000*. By directly counting the variation obtained from
      these ultradeep sequencing reads, we found that A -> G was the predominant single
      base substitution and 1 bp deletions were the major small indel. These patterns
      are completely different from those obtained by comparison of closely related S.
      aureus strains, where C -> T accounted for a larger proportion of mutations and
      deletions were shown to occur at an almost equal frequency to insertion. These
      findings suggest that the genomic differences between closely related bacterial
      strains have already undergone selection and are therefore not representative of
      spontaneous mutation.

PMID- 23531727
TI  - Crying with sorrow evoked by electrocortical stimulation.
AB  - Dacrystic seizures are rare and have been reported in patients with hypothalamic
      hamartoma as well as fronto-temporal epilepsy, involving the non-dominant
      hemisphere. We describe the first reported case of cortical stimulation of the
      left posterior orbito-frontal gyrus, generating consistent and reproducible
      crying with affective content in a 41-year-old woman with medically intractable
      left temporal lobe epilepsy, who underwent extraoperative intracranial video-EEG
      monitoring for resective non-lesional epilepsy surgery.

PMID- 23531728
TI  - Intracranial pressure monitoring in severe traumatic brain injury: who is still
      bold enough to keep sinning against the level I evidence?

PMID- 23531729
TI  - Intracranial pressure monitoring in severe traumatic brain injury.

PMID- 23531730
TI  - Recurrent dermatofibrosarcoma protuberans with pulmonary metastases presenting
      twelve years after initial diagnosis: 18F-FDG PET/CT imaging findings.
AB  - Dermatofibrosarcoma protuberans is a rare cutaneous tumor that is locally
      aggressive and has a high rate of recurrence after surgical excision. The tumor
      grows slowly, typically over years. On rare occasions, metastasis to distant
      sites (especially the lung) or regional lymph nodes may occur. Here, we present F
      FDG PET/CT imaging findings of a 52-year-old man with a local recurrence of
      dermatofibrosarcoma protuberans in the anterior abdominal wall with metastases to
      bilateral lungs. 

PMID- 23531731
TI  - PET/CT appearance of acute pyelonephritis.
AB  - An 18-year-old male patient with a history of Ewing sarcoma originally involving
      the right ilium was evaluated with an FDG PET/CT scan to evaluate the effect of
      salvage therapy after standard treatment failed and disease progressed to involve
      the right T12 pedicle. Autologous stem cell transplantation and cyberknife
      therapy resulted in mixed tumor response, with incidental note made of prominent
      areas of cortical FDG avidity in the right kidney. These regions demonstrated
      focal hypoenhancement on the corresponding diagnostic contrast-enhanced CT, which
      additionally demonstrated peripheral enhancement spanning the length of the right
      ureter. Clinical workup produced a diagnosis of acute pyelonephritis.

PMID- 23531732
TI  - 68Ga DOTATATE PET/CT uptake in spinal lesions and MRI correlation on a patient
      with neuroendocrine tumor: potential pitfalls.
AB  - A 62-year-old female patient with suspected insulinoma underwent 68Ga DOTA-TATE
      PET/CT for characterization and staging. This demonstrated a focus of uptake in
      the pancreas and 3 foci of uptake in the spine. An MRI of the spine performed to
      further characterize the lesions revealed the presence of a meningioma and
      degenerative changes, both of which showed 68Ga DOTA-TATE uptake. A vertebral
      metastasis seen on PET was occult on CT and MRI. A vertebral hemangioma had no
      discrete tracer uptake. Awareness of sources of error in interpreting 68Ga DOTA
      TATE scans is important in order to avoid pitfalls.

PMID- 23531733
TI  - Usefulness of (18)F-FDG PET/CT in a rare case of malignant pseudothyroiditis.
AB  - We report an unusual case of malignant pseudothyroiditis (MPT) occurred in a 35
      year-old female patient presenting with symptoms and signs of thyroiditis. Fine
      needle aspiration biopsy of the thyroid demonstrated the presence of a MPT
      induced by a metastatic extrathyroidal carcinoma. F-FDG-PET/CT showed increased
      radiopharmaceutical uptake in the thyroid, in multiple cervical and mediastinal
      lymph nodes, and in a right pulmonary nodule. Histological examination
      demonstrated the presence of a metastatic non-small cell lung cancer (NSCLC). In
      this unusual case of MPT F-FDG-PET/CT has been useful in staging the disease and
      in detecting the primary tumor site. 

PMID- 23531734
TI  - Progressive presynaptic dopaminergic deterioration in Huntington disease: a
      [123I]-FP-CIT SPECT two-year follow-up study.
AB  - To illustrate the potential of [I]-FP-CIT SPECT DaTSCAN(r) in investigating the
      progression of presynaptic dopaminergic degeneration in Huntington disease (HD),
      we performed a 2-year follow-up [I]-FP-CIT study on 4 HD patients, evaluating the
      SPECT imaging based on qualitative and semiquantitative analysis. The mean annual
      decline in [I]-FP-CIT uptake in caudate and putamen after 2 years of follow-up
      was 5.8% and 9.6%, respectively. Our findings suggest that [I]-FP-CIT SPECT is
      useful in investigating the progression of presynaptic dopaminergic degeneration
      in HD, and may be useful as a disease biomarker, providing an objective method
      for measuring the effectiveness of future neuroprotective therapies. 

PMID- 23531735
TI  - Role of SPECT/CT compared with MRI in the diagnosis and management of patients
      with wrist trauma occult fractures.
AB  - BACKGROUND: The diagnosis of wrist fractures, especially scaphoid fractures,
      remains a challenge because of nonunion risk. Currently, new hybrid technologies
      are emerging such as SPECT/CT systems, which combine functional and anatomical
      data sets. So, we wanted to evaluate the utility of SPECT/CT in the management of
      occult carpal fractures. METHODS: In this study, all patients addressed at the
      orthopedic department at Brest University Hospital for wrist pain after trauma
      with initial normal plain radiographs were prospectively included. Patients with
      normal radiographs but with signs strongly suggestive of clinical fracture
      underwent a bone SPECT/CT and an MRI of the wrist. Therapeutic management took
      into account the results of all modalities, and all patients were followed up for
      at least 6 months and reviewed by the same surgeon. SPECT/CT findings were
      compared with those of the other modalities and follow-up. RESULTS: From December
      2009 to May 2011, 57 patients were enrolled. Fifty-seven SPECT/CT and 52 MRI
      scans were obtained. Twenty-eight patients had normal imaging results, whereas 29
      patients presented bone bruise and/or fractures. Ten patients were concordant
      according to SPECT/CT and MRI; 2 patients presented fractures on SPECT/CT without
      MRI performed; 17 patients had partially discordant results. Only 1 patient
      presented a nonunion at the follow-up, whereas both investigations were positive.
      CONCLUSIONS: This study highlights the good performances of SPECT/CT, which
      allows the detection of most occult carpal fractures. When a carpal occult
      fracture is strongly suspected clinically, SPECT/CT might be proposed at first
      intention after normal radiographs.

PMID- 23531736
TI  - Classical skeletal injuries shown on 18F-FDG PET/CT following successful
      cardiopulmonary resuscitation.
AB  - Rib and sternal fractures are relatively common following conventional
      cardiopulmonary resuscitation (CPR). This case demonstrates the 18F-FDG PET/CT
      appearances of typical CPR-related multiple rib and sternal fractures in a 55
      year-old man with suspected cardiac sarcoidosis. The PET/CT scan was performed to
      assess disease activity of cardiac sarcoidosis, and no active cardiac
      inflammation was detected. The patient initially presented with an out-of
      hospital cardiac arrest and successfully received bystander CPR.

PMID- 23531737
TI  - Prognostic importance of 18F-FDG uptake pattern of hepatocellular cancer patients
      who received SIRT.
AB  - PURPOSE: The aim of the study was to evaluate the effect of 18F-FDG uptake
      pattern of liver lesions to treatment response of patients who received yttrium
      90 (Y-90) selective internal radiation therapy (SIRT) for hepatocellular cancer
      (HCC). PATIENTS AND METHODS: Nineteen patients (5F, 14M, mean age: 64.5 +/- 14.7
      years old, range: 57-73 years) who received SIRT treatment in our department for
      HCC between June 2008 and May 2011 were included in the study. All patients
      underwent 18F-FDG PET/CT before SIRT for evaluation of disease stage and
      metabolic activity of liver lesions. Patients were divided into 3 groups
      according to FDG uptake patterns of primary liver lesions (hypoactive,
      nonhomogenous, and focal intense). Progression-free survival (PFS) times of each
      group and patients with hepatic only and hepatic with extrahepatic disease were
      analyzed. Disease progression criteria were increase in tumor volume, progressive
      elevation of serum alpha-fetoprotein levels, and detection of extrahepatic
      metastases. Kaplan-Meier analysis was used for comparison of PFS times. RESULTS:
      The mean treatment dose was calculated as 1.4 +/- 1.0 GBq. While liver lesions of
      4 patients were hypoactive in pretreatment 18F-FDG PET/CT, liver lesions of 6 and
      9 patients had nonhomogenous and intense FDG uptake, respectively. Mean PFS time
      of patients who had hypoactive liver lesions was 5.25 +/- 1.52 months. In
      patients who had liver lesions with nonhomogenous uptake, mean PFS time was 12.3
      +/- 2.6 months. Lastly, in patients with intense uptake in liver lesions, PFS
      time was calculated as 19.8 +/- 5.0 months. Difference between each group was
      statistically significant (P = 0.017). There was no significant difference in the
      PFS of the patients with limited hepatic disease and patients with extrahepatic
      involvement. CONCLUSION: In patients with unresectable HCC, higher SUVmax lesions
      unexpectedly had better PFS rates after SIRT, suggesting SIRT has a treatment
      advantage over other therapeutic options in these patients.

PMID- 23531738
TI  - Usefulness of SPECT/CT for equivocal findings on (131)I whole-body scan in a
      patient with differentiated papillary thyroid cancer.
AB  - A 42-year-old female patient who underwent right central compartment node
      dissection owing to recurrence of differentiated papillary thyroid carcinoma
      received 150 mCi of I as an adjuvant therapy. Uptake was observed at the thyroid
      bed and right lower neck, suggesting thyroid remnant tissues and/or lymph node
      metastasis on a whole-body scan obtained 5 days after I administration. SPECT/CT
      was performed and the uptake at the right lower neck was finally diagnosed as a
      lung metastasis. This case illustrates the benefit of SPECT/CT for a patient with
      equivocal findings on an I planar image. 

PMID- 23531739
TI  - Incidental scintigraphic finding of ovarian teratoma containing normal thyroid
      tissue on post-radioactive iodine therapy for papillary thyroid cancer.
AB  - Abnormal focal uptakes are often visualized on I post-treatment scintigraphy in
      case of differentiated thyroid carcinoma. For some of these, especially on
      atypical localization, it can be difficult to affirm the benign or malignant
      nature. A high serum thyroglubulin value after surgery may suggest the presence
      of metastatic disease. We report a case of an abnormal ovarian uptake on post
      treatment scintigraphy associated with an elevated thyroglobulin value revealing
      finally an ovarian mature cystic teratoma containing normal thyroid tissue.

PMID- 23531740
TI  - FDG PET/CT imaging of extrapulmonary small cell carcinoma of the adrenal gland.
AB  - Extrapulmonary small cell carcinoma (SCC) is an uncommon malignancy. A 57-year
      old man was referred because of a 1-month history of left lumbago. MR images
      showed an ovoid tumor in the left adrenal gland. FDG PET/CT showed intense FDG
      uptake of the left adrenal tumor with thrombosis of the left renal vein. The
      patient underwent left adrenalectomy and nephrectomy. Histopathology revealed
      typical adrenal SCC with neoplastic thrombosis of the left renal vein. This case
      suggests that FDG PET/CT is useful for staging of extrapulmonary SCC. 

PMID- 23531741
TI  - FDG PET/CT findings in a case of nontuberculous abscess of adrenal gland.
AB  - Abscesses in the adrenal gland are extremely rare in adults with few cases
      reported in literature. We report FDG PET/CT findings in a unilateral adrenal
      abscess in a case of hepatocellular carcinoma. Though rare, this diagnosis should
      be kept in mind while evaluating cystic lesions of adrenal gland on PET/CT.
      Correlation with clinical picture and blood investigations is useful in such
      cases. 

PMID- 23531742
TI  - Voltage-gated sodium channels: pharmaceutical targets via anticonvulsants to
      treat epileptic syndromes.
AB  - Epilepsy is a brain disorder characterized by seizures and convulsions. The basis
      of epilepsy is an increase in neuronal excitability that, in some cases, may be
      caused by functional defects in neuronal voltage gated sodium channels, Nav1.1
      and Nav1.2. The effects of antiepileptic drugs (AEDs) as effective therapies for
      epilepsy have been characterized by extensive research. Most of the classic AEDs
      targeting Nav share a common mechanism of action by stabilizing the channel's
      fast-inactivated state. In contrast, novel AEDs, such as lacosamide, stabilize
      the slow-inactivated state in neuronal Nav1.1 and Nav1.7 isoforms. This paper
      reviews the different mechanisms by which this stabilization occurs to determine
      new methods for treatment.

PMID- 23531743
TI  - Traffic-related air pollution and prostate cancer risk: a case-control study in
      Montreal, Canada.
AB  - OBJECTIVES: There is a paucity of information on environmental risk factors for
      prostate cancer. We conducted a case-control study in Montreal to estimate
      associations with exposure to ground-level nitrogen dioxide (NO2), a marker for
      traffic-related air pollution. METHODS: Cases were 803 men with incident prostate
      cancer, <=75 years of age, and diagnosed across all French hospitals in Montreal.
      Concurrently, 969 controls were drawn from electoral lists of French-speaking
      individuals residing in the same electoral districts as the cases and frequency
      matched by age. Concentrations of NO2 were measured across Montreal in 2005-2006.
      We developed a land use regression model to predict concentrations of NO2 across
      Montreal for 2006. These estimates were back-extrapolated to 1996. Estimates were
      linked to residential addresses at the time of diagnosis or interview.
      Unconditional logistic regression was used, adjusting for potential confounding
      variables. RESULTS: For each increase of 5 parts per billion of NO2, as estimated
      from the original land use regression model in 2006, the OR5ppb adjusted for
      personal factors was 1.44 (95% CI 1.21 to 1.73). Adding in contextual factors
      attenuated the OR5ppb to 1.27 (95% CI 1.03 to 1.58). One method for back
      extrapolating concentrations of NO2 to 1996 (about 10 years before the index
      date) gave the following OR5ppb: 1.41 (95% CI 1.24 to 1.62) when personal factors
      were included, and 1.30 (95% CI 1.11 to 1.52) when contextual factors were added.
      CONCLUSIONS: Exposure to ambient concentrations of NO2 at the current address was
      associated with an increased risk of prostate cancer. This novel finding requires
      replication.

PMID- 23531744
TI  - Synthesis and characterization of bovine serum albumin-copper nanocomposites for
      antibacterial applications.
AB  - A method for the synthesis of bovine serum albumin (BSA) and copper (Cu(0))
      nanocomposites is described. The synthesis is achieved by adding [100mM]
      hydrazine hydrate ((N2H4.H2O) to [10mM] copper sulfate (CuSO4.5H2O) solution in
      the presence of 0.02% bovine serum albumin at pH-10.0 and then heating the
      reaction mixture at 50 degrees C for 3h. The process resulted into the formation
      of well-dispersed hexagonal Cu-BSA composite particles (size 5+/-2.5) MUm
      consisting of embedded copper nanoparticles (Cu NPs). The nanoparticles embedded
      in composite were of average diameters of 28+/-12nm. Phase analysis, purity and
      morphology of the product have been studied by various physical techniques.
      Effect of various reaction parameters have been investigated on the morphology of
      synthesized nanocomposite. Efforts have been made to investigate the possible
      mechanism of Cu-BSA composite synthesis which gave it unique hexagonal
      morphology. The important characteristic of the reported method is that the
      highly stable Cu NPs present in composite were synthesized without any inert
      atmosphere which could be dried under vacuum and stored for long term use. The
      synthesized Cu NPs containing BSA composite material exhibited good antibacterial
      potential against both Gram positive and Gram negative bacterial strains. The
      minimum inhibitory concentration (MIC) of Cu NPs in the form Cu-BSA composite on
      Escherichia coli was calculated to be 50MUgmL(-1). Transmission electron
      microscopic and cytoplasmic leakage analysis revealed that Cu-BSA composite
      attached to the bacteria causing irreversible membrane damage leading to leakage
      of intracellular metabolites and eventually death of the organism.

PMID- 23531745
TI  - SISCOM and FDG-PET in patients with non-lesional extratemporal epilepsy:
      correlation with intracranial EEG, histology, and seizure outcome.
AB  - AIMS: To assess the practical localising value of subtraction ictal single-photon
      emission computed tomography (SISCOM) coregistered with MRI and (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with
      extratemporal epilepsy and normal MRI. METHODS: We retrospectively studied a
      group of 14 patients who received surgery due to intractable epilepsy and who
      were shown to have focal cortical dysplasia, undetected by MRI, based on
      histological investigation. We coregistered preoperative SISCOM and PET images
      with postoperative MRI and visually determined whether the SISCOM focus, PET
      hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on
      intracranial EEG, were removed completely, incompletely, or not at all. These
      results and histopathological findings were compared with postoperative seizure
      outcome. RESULTS: Two patients underwent one-stage multimodal image-guided
      surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings
      were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom
      had favourable postsurgical outcome (Engel class I and II). Complete resection of
      the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical
      regions with intracranial EEG abnormalities (n=7) were predictive of favourable
      postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients
      with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of
      7 patients with incomplete resection and 1 of 2 with no resection of the PET
      hypometabolic area; and 2 of 7 patients with incomplete resection of the area
      corresponding to intracranial EEG abnormality. No correlation between
      histopathological FCD subtype and seizure outcome was observed. CONCLUSION:
      Complete resection of the dysplastic cortex localised by SISCOM, FDG-PET or
      intracranial EEG is a reliable predictor of favourable postoperative seizure
      outcome in patients with non-lesional extratemporal epilepsy.

PMID- 23531746
TI  - Analysis of protein glycation using fluorescent phenylboronate gel
      electrophoresis.
AB  - Glycated proteins are important biomarkers for age-related disorders, however
      their analysis is challenging because of the complexity of the protein
      carbohydrate adducts. Here we report a method that enables the detection and
      identification of individual glycated proteins in complex samples using
      fluorescent boronic acids in gel electrophoresis. Using this method we identified
      glycated proteins in human serum, insect hemolymph and mouse brain homogenates,
      confirming this technique as a powerful proteomics tool that can be used for the
      identification of potential disease biomarkers.

PMID- 23531749
TI  - Faculty supervision of residents--creating important moments of magic.

PMID- 23531748
TI  - Validation of electronic medical record-based phenotyping algorithms: results and
      lessons learned from the eMERGE network.
AB  - BACKGROUND: Genetic studies require precise phenotype definitions, but electronic
      medical record (EMR) phenotype data are recorded inconsistently and in a variety
      of formats. OBJECTIVE: To present lessons learned about validation of EMR-based
      phenotypes from the Electronic Medical Records and Genomics (eMERGE) studies.
      MATERIALS AND METHODS: The eMERGE network created and validated 13 EMR-derived
      phenotype algorithms. Network sites are Group Health, Marshfield Clinic, Mayo
      Clinic, Northwestern University, and Vanderbilt University. RESULTS: By
      validating EMR-derived phenotypes we learned that: (1) multisite validation
      improves phenotype algorithm accuracy; (2) targets for validation should be
      carefully considered and defined; (3) specifying time frames for review of
      variables eases validation time and improves accuracy; (4) using repeated
      measures requires defining the relevant time period and specifying the most
      meaningful value to be studied; (5) patient movement in and out of the health
      plan (transience) can result in incomplete or fragmented data; (6) the review
      scope should be defined carefully; (7) particular care is required in combining
      EMR and research data; (8) medication data can be assessed using claims,
      medications dispensed, or medications prescribed; (9) algorithm development and
      validation work best as an iterative process; and (10) validation by content
      experts or structured chart review can provide accurate results. CONCLUSIONS:
      Despite the diverse structure of the five EMRs of the eMERGE sites, we developed,
      validated, and successfully deployed 13 electronic phenotype algorithms.
      Validation is a worthwhile process that not only measures phenotype performance
      but also strengthens phenotype algorithm definitions and enhances their inter
      institutional sharing.

PMID- 23531750
TI  - Advancing the medical education mission: the bottom line.

PMID- 23531747
TI  - Tumor Necrosis Factor-alpha: Life and Death of Hepatocytes During Liver
      Ischemia/Reperfusion Injury.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory
      cytokine involved in a variety of disease pathologies, including
      ischemia/reperfusion (I/R) injuries in transplantation. The interaction of TNF
      alpha with its cognate receptor TNF receptor I (TNFRI) results in the activation
      of signal transduction pathways that regulate either cell survival or cell death.
      Hepatocytes express TNFRI and respond to TNF-alpha released by resident Kupffer
      cells as well as leukocytes that migrate to the liver during I/R injury. Upon
      binding TNF-alpha, the hepatocyte proliferates or undergoes apoptosis or
      necroptosis. The decision by the cell to commit to one path or the other is not
      understood. The damaged tissue exhibits cell death and hemorrhaging from the
      influx of immune mediators. TNF-alpha inhibitors ameliorate the injury in animal
      models, suggesting that lowering (but not eliminating) TNF-alpha levels shifts
      the balance of TNF-alpha toward its beneficial functions. METHODS: We review TNF
      alpha signal transduction pathways and the role of TNF-alpha in liver I/R injury.
      CONCLUSIONS: Because TNF-alpha plays an important role in hepatocyte
      proliferation, complete inhibition of TNF-alpha is not desirable in treating
      liver I/R injury. The strategy for developing pharmacological therapies may be
      the identification of specific intermediates in the TNF-alpha/TNFR1 signal
      transduction pathway and directed targeting of proapoptotic and pronecroptotic
      events.

PMID- 23531751
TI  - Why reforms must be made to make the dean's letter useful.

PMID- 23531752
TI  - In reply to Weissman.

PMID- 23531753
TI  - Why we must teach written and verbal communication skills to medical students and
      residents.

PMID- 23531754
TI  - Insomnia from disease or disaster?

PMID- 23531755
TI  - In reply to Kunimatsu and Yoshizawa.

PMID- 23531756
TI  - Fostering a new vision of health by incorporating human rights training into
      medical education.

PMID- 23531757
TI  - The next generation of doctoring.
AB  - The authors reflect on the creation of the Doctoring program at the UCLA School
      of Medicine two decades ago. Although Doctoring--at UCLA and other institutions
      where it has been implemented--has successfully taught large numbers of students
      psychosocial content and communications skills that are often overlooked in
      traditional medical school curricula and has had an impact on the larger culture
      of medical education, the authors believe that its full promise remains
      unfulfilled. Of the many practical difficulties they encountered in creating and
      implementing this comprehensive program, the greatest barriers, by far, were
      cultural. The authors argue that the impact of programs like Doctoring-programs
      that attempt not only to change the content of what students learn but also to
      encourage students to think critically and to question fundamental aspects of the
      way medicine is taught, learned, and practiced-cannot grow unless and until the
      larger culture of medicine also changes. They offer recommendations for
      overcoming barriers to improve the next generation of Doctoring and similar
      programs; these include changing the philosophy behind the selection of medical
      students, providing far greater resources and support for course faculty, and
      altering incentives for medical school faculty. They conclude that until major
      cultural and structural barriers are overcome and the values that Doctoring and
      like programs attempt to engender become the primary values of the larger culture
      they seek to change, these programs will continue in fundamental ways to function
      outside the dominant culture of medicine.

PMID- 23531759
TI  - Milly.

PMID- 23531760
TI  - Medicine and the arts. Science and charity: by Pablo Picasso. Commentary.

PMID- 23531762
TI  - AM last page. Quality criteria in qualitative and quantitative research.

PMID- 23531763
TI  - GPU-Accelerated Forward and Back-Projections with Spatially Varying Kernels for
      3D DIRECT TOF PET Reconstruction.
AB  - We describe a GPU-accelerated framework that efficiently models spatially (shift)
      variant system response kernels and performs forward- and back-projection
      operations with these kernels for the DIRECT (Direct Image Reconstruction for
      TOF) iterative reconstruction approach. Inherent challenges arise from the poor
      memory cache performance at non-axis aligned TOF directions. Focusing on the GPU
      memory access patterns, we utilize different kinds of GPU memory according to
      these patterns in order to maximize the memory cache performance. We also exploit
      the GPU instruction-level parallelism to efficiently hide long latencies from the
      memory operations. Our experiments indicate that our GPU implementation of the
      projection operators has slightly faster or approximately comparable time
      performance than FFT-based approaches using state-of-the-art FFTW routines.
      However, most importantly, our GPU framework can also efficiently handle any
      generic system response kernels, such as spatially symmetric and shift-variant as
      well as spatially asymmetric and shift-variant, both of which an FFT-based
      approach cannot cope with.

PMID- 23531764
TI  - Contribution of bone marrow derived cells to the pancreatic tumor
      microenvironment.
AB  - Pancreatic cancer is a complex, aggressive, and heterogeneous malignancy driven
      by the multifaceted interactions within the tumor microenvironment. While it is
      known that the tumor microenvironment accommodates many cell types, each playing
      a key role in tumorigenesis, the major source of these stromal cells is not well
      understood. This review examines the contribution of bone marrow-derived cells
      (BMDC) to pancreatic carcinogenesis, with respect to their role in constituting
      the tumor microenvironment. In particular, their role in supporting fibrosis,
      immunosuppression, and neovascularization will be discussed.

PMID- 23531765
TI  - Peripheral dose measurements with diode and thermoluminescence dosimeters for
      intensity modulated radiotherapy delivered with conventional and un-conventional
      linear accelerator.
AB  - The objective of this paper was to measure the peripheral dose (PD) with diode
      and thermoluminescence dosimeter (TLD) for intensity modulated radiotherapy
      (IMRT) with linear accelerator (conventional LINAC), and tomotherapy (novel
      LINAC). Ten patients each were selected from Trilogy dual-energy and from Hi-Art
      II tomotherapy. Two diodes were kept at 20 and 25 cm from treatment field edge.
      TLDs (LiF:MgTi) were also kept at same distance. TLDs were also kept at 5, 10,
      and 15 cm from field edge. The TLDs were read with REXON reader. The readings at
      the respective distance were recorded for both diode and TLD. The PD was
      estimated by taking the ratio of measured dose at the particular distance to the
      prescription dose. PD was then compared with diode and TLD for LINAC and
      tomotherapy. Mean PD for LINAC with TLD and diode was 2.52 cGy (SD 0.69), 2.07
      cGy (SD 0.88) at 20 cm, respectively, while at 25 cm, it was 1.94 cGy (SD 0.58)
      and 1.5 cGy (SD 0.75), respectively. Mean PD for tomotherapy with TLD and diode
      was 1.681 cGy SD 0.53) and 1.58 (SD 0.44) at 20 cm, respectively. The PD was 1.24
      cGy (SD 0.42) and 1.088 cGy (SD 0.35) at 25 cm, respectively, for tomotherapy.
      Overall, PD from tomotherapy was found lower than LINAC by the factor of 1.2-1.5.
      PD measurement is essential to find out the potential of secondary cancer. PD for
      both (conventional LINAC) and novel LINACs (tomotherapy) were measured and
      compared with each other. The comparison of the values for PD presented in this
      work and those published in the literature is difficult because of the different
      experimental conditions. The diode and TLD readings were reproducible and both
      the detector readings were comparable.

PMID- 23531766
TI  - The Big Five of Personality and structural imaging revisited: a VBM - DARTEL
      study.
AB  - The present study focuses on the neurostructural foundations of the human
      personality. In a large sample of 227 healthy human individuals (168 women and 59
      men), we used MRI to examine the relationship between personality traits and both
      regional gray and white matter volume, while controlling for age and sex.
      Personality was assessed using the German version of the NEO Five-Factor
      Inventory that measures individual differences in the 'Big Five of Personality':
      extraversion, neuroticism, agreeableness, conscientiousness, and openness to
      experience. In contrast to most previous studies on neural correlates of the Big
      Five, we used improved processing strategies: white and gray matter were
      independently assessed by segmentation steps before data analysis. In addition,
      customized sex-specific diffeomorphic anatomical registration using exponentiated
      lie algebra templates were used. Our results did not show significant
      correlations between any dimension of the Big Five and regional gray matter
      volume. However, among others, higher conscientiousness scores correlated
      significantly with reductions in regional white matter volume in different brain
      areas, including the right insula, putamen, caudate, and left fusiformis. These
      correlations were driven by the female subsample. The present study suggests that
      many results from the literature on the neurostructural basis of personality
      should be reviewed carefully, considering the results when the sample size is
      larger, imaging methods are rigorously applied, and sex-related and age-related
      effects are controlled.

PMID- 23531768
TI  - 68Ga-DOTANOC PET-CT demonstrating in vivo somatostatin receptor expression in
      idiopathic gynecomastia.
AB  - Gynecomastia is abnormal enlargement of the male breasts due to the excess growth
      of glandular component. A 65-year-old man with medullary carcinoma of thyroid
      underwent (68)Ga-DOTANOC PET-CT for somatostatin receptor (SSTR) scintigraphy.
      Extensive nodal, bone, and bone marrow disease was seen. Interestingly, increased
      (68)Ga-DOTANOC uptake was also noted in bilateral enlarged mammary glands
      (gynecomastia). Although SSTR types 1 and 3 have been identified in the normal
      female breast, no report exists regarding SSTR expression in gynecomastia.

PMID- 23531767
TI  - Integrative analysis of C. elegans modENCODE ChIP-seq data sets to infer gene
      regulatory interactions.
AB  - The C. elegans modENCODE Consortium has defined in vivo binding sites for a large
      array of transcription factors by ChIP-seq. In this article, we present examples
      that illustrate how this compendium of ChIP-seq data can drive biological
      insights not possible with analysis of individual factors. First, we analyze the
      number of independent factors bound to the same locus, termed transcription
      factor complexity, and find that low-complexity sites are more likely to respond
      to altered expression of a single bound transcription factor. Next, we show that
      comparison of binding sites for the same factor across developmental stages can
      reveal insight into the regulatory network of that factor, as we find that the
      transcription factor UNC-62 has distinct binding profiles at different stages due
      to distinct cofactor co-association as well as tissue-specific alternative
      splicing. Finally, we describe an approach to infer potential regulators of gene
      expression changes found in profiling experiments (such as DNA microarrays) by
      screening these altered genes to identify significant enrichment for targets of a
      transcription factor identified in ChIP-seq data sets. After confirming that this
      approach can correctly identify the upstream regulator on expression data sets
      for which the regulator was previously known, we applied this approach to
      identify novel candidate regulators of transcriptional changes with age. The
      analysis revealed nine candidate aging regulators, of which three were previously
      known to have a role in longevity. We experimentally showed that two of the new
      candidate aging regulators can extend lifespan when overexpressed, indicating
      that this approach can identify novel functional regulators of complex processes.

PMID- 23531769
TI  - Correlative imaging with (18)F-FDG PET/CT and MRI in paraneoplastic limbic
      encephalitis.
AB  - Limbic encephalitis is one of the most common paraneoplastic neurological
      syndromes, which is mostly associated with small cell lung cancer, testicular
      tumors, and breast cancer. F-FDG PET/CT can have an important role both in the
      identification of limbic encephalitis itself and in the detection of the unknown
      malignancy that might have caused it. We report a case of a 57-year-old female
      patient with paraneoplastic limbic encephalitis, confirmed both by MRI and F-FDG
      PET/CT, and the concurrent identification of an unknown lung malignancy by whole
      body PET/CT.

PMID- 23531770
TI  - Autonomous functioning thyroid nodules and 131I in diagnosis and therapy after 50
      years of experience: what is still open to debate?
AB  - PURPOSE OF THE REPORT: Autonomous functioning thyroid nodules (AFTN), defined as
      "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim
      of our study was to investigate the long-term outcome in patients treated with an
      131I calculated dose, to identify a possible "size-tailored" dose, and to
      simplify follow-up procedures. PATIENTS AND METHODS: Retrospective analysis was
      carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an
      131I calculated dose. Our study focused on nodular size and mean administered
      dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from
      treatment was considered. RESULTS: A single 131I dose was effective for the vast
      majority of patients (93%). The outcome was influenced by nodular size. On the
      basis of the Italian dose limit for outpatient treatment, our population was
      divided into subgroups according to administered doses (more or less than 16 mCi)
      and nodular dimensions: no differences in outcome were observed for each class of
      nodule size. A dose <=10 mCi was effective on the smaller nodules (50.1% of our
      population). The agreement between TSH and scan after treatment was 90.3% at 3
      months and 94.5% at 6 months. CONCLUSIONS: 131I therapy with a calculated dose is
      an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often
      resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are
      eligible for surgery. TSH is the only parameter required to evaluate the outcome.

PMID- 23531771
TI  - Bilateral lung 99mTc-MDP uptake on the bone scintigraphy in the myelodysplastic
      syndromes (MDS).
AB  - We report a case of myelodysplastic syndrome (MDS) with unusual abnormal 99mTc
      MDP activity throughout both lungs on whole-body bone scan. To explain the
      pancytopenia, bone marrow examination was carried out which showed
      hypocellularity in addition to large abnormal megakaryocytes indicating
      myelodysplastic changes. His whole-body bone scan showed increased 99mTc-MDP
      activity in both lungs, kidneys, and also along the proximal two thirds of the
      femora. It was concluded that lung uptake in addition to skeletal uptake on
      scintigraphic bone scanning should be kept in mind in patients with MDS.

PMID- 23531772
TI  - Comparison of 99mTc-HYNIC-TOC and HYNIC-TATE octreotide scintigraphy with FDG PET
      and 99mTc-MIBI in local recurrent or distant metastatic thyroid cancers.
AB  - AIM: There have been various studies for early diagnosis of local recurrent or
      distant metastatic thyroid cancers. The aim of this study is to evaluate the
      clinical utility of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, octreotide derivatives,
      to detect recurrences or distant metastases in 131I-negative thyroglobulin
      positive thyroid cancer patients and to compare the lesions with FDG PET and
      99mTc-MIBI studies in the same patient group. PATIENTS AND METHODS: Twenty
      differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 +/-
      15.3 (range 13-78 years), were included in this study. Eighteen patients had
      papillary thyroid cancer and 2 had follicular thyroid cancer. Fifteen patients
      received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical.
      All patients underwent whole-body scan 1 and 4 hours after injection of
      octreotide derivatives and SPECT imagings were performed from the suspicious
      sites. The lesions that were seen in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE studies
      were compared with 99mTc-MIBI and FDG-PET studies. RESULTS: Among 99mTc-HYNIC-TOC
      and 99mTc-HYNIC-TATE scintigraphies, 15 patient studies were evaluated as true
      positive (75%) and 5 were false negative (25%). The total number of lesions in
      octreotide scintigraphy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET
      study, 15 of them were evaluated as true positive (78.9%), and 4 them were
      evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74.
      99mTc-MIBI study was positive in 11 patients (55%) and negative in 9 patients
      (45%). Total number of lesions in 99mTc-MIBI was 25. CONCLUSION: Technetium
      labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are
      useful imaging alternatives in somatostatin receptor expressing thyroid cancer
      patients. Radiolabeling is easy and they are readily available for routine use.

PMID- 23531773
TI  - Utility of 18F-FDG PET/CT in diagnosis and management of mucormycosis.
AB  - (18)F-FDG PET/CT on a 23-year-old woman with aplastic anemia and left periorbital
      swelling showed FDG-avid lesions in the head and neck. The lesions were confirmed
      to be mucormycosis histologically after (18)F-FDG PET/CT-guided biopsy.
      Antifungal therapy was adjusted with serial follow-up (18)F-FDG PET/CT until
      complete patient recovery. (18)F-FDG PET/CT is valuable in the diagnosis and
      management of mucormycosis.

PMID- 23531774
TI  - Comparison of FDG PET/CT and gadolinium-enhanced MRI for the detection of bone
      metastases in patients with cancer: a meta-analysis.
AB  - OBJECTIVE: At present, the differences in the efficacy between PET/CT and MRI for
      the detection of bone metastases in patients with cancer have not been clearly
      delineated. We performed a meta-analysis to compare the performance of FDG PET/CT
      with that of gadolinium-enhanced MRI for the detection of bone metastases in
      patients with cancer. METHODS: Studies about PET/CT and MRI for the detection of
      bone metastases were systematically searched in the MEDLINE, EMBASE, and EBM
      Review databases. We calculated sensitivities, specificities, diagnostic odds
      ratios, positive likelihood ratios, negative likelihood ratios (NLR), and
      constructed summary receiver operating characteristic curves using bivariate
      regression models for PET/CT and MRI, respectively. RESULTS: Across 9 studies
      (1116 patients), FDG PET/CT has similar patient-based sensitivity (0.803 vs
      0.837), specificity (0.989 vs 0.977), diagnostic odds ratio (309.0 vs 221.9),
      positive likelihood ratio (61.7 vs 37.0), and negative likelihood ratio (0.200 vs
      0.167) with gadolinium-enhanced MRI. Areas under the curve with 95% confidence
      interval for FDG PET/CT and gadolinium-enhanced MRI were 0.99 (0.98-0.99) and
      0.98 (0.97-0.99), respectively. CONCLUSIONS: FDG PET/CT and gadolinium-enhanced
      MRI have excellent diagnostic performance for the detection of bone metastases in
      patients with cancer.

PMID- 23531775
TI  - Successful localization of residual culprit tumor in a case of tumor-induced
      osteomalacia using 68Ga-DOTANOC PET/CT.
AB  - Tumor-induced osteomalacia (TIO) is a rare disease entity characterized by
      clinical pictures of recurrent multiple fractures and biochemical features of
      phosphaturia, hypophosphatemia, and low vitamin D levels. Most often TIO is
      caused by benign soft tissue tumors. The main issue in management of such
      patients is proper tumor localization, as these tumors are small and often
      located at obscure sites. We describe a case of TIO where residual disease was
      clinically suspected after tumor resection and subsequently detected using Ga
      DOTANOC PET/CT. 

PMID- 23531776
TI  - In the era of recombinant BMP, does additional anterior stabilization add value
      to a posterolateral fusion?
AB  - STUDY DESIGN:  Retrospective cohort study. Clinical question or objective: Is
      there a benefit to additional transforaminal lumbar interbody fusion (TLIF) if a
      solid posterolateral (PL) fusion can be achieved with routine bone morphogenetic
      protein (BMP) use in low-grade spondylolisthesis? METHODS:  We performed a
      retrospective review of patients who had undergone surgery for grade I or II
      lumbar spondylolisthesis stratified into two groups. Group 1 had 46 patients who
      underwent TLIF along with PL instrumented fusion. Group 2 had 40 patients who
      underwent PL instrumented fusion alone. In both groups, adequate posterior
      decompression with pedicle screw instrumentation was performed and rhBMP-7 was
      used. All patients were evaluated clinically using the Oswestry Disability Index
      (ODI) and by independent radiological examination at 3 and 12 months. RESULTS: 
      At a minimum follow-up of 12 months, there was no statistically significant
      difference in the rate of fusion. In addition, there were no differences in the
      proportion of patients who had a minimal clinically significant difference in
      their ODI. There was a similar rate of complications between each cohort.
      CONCLUSIONS:  The use of BMP was associated with a high rate of PL lumbar fusion.
      In the presence of a PL fusion, there appears to be little clinical benefit to
      additional anterior TLIF in degenerative spondylolisthesis. [Table: see text].

PMID- 23531777
TI  - Differential sperm expenditure reveals a possible role for post-copulatory sexual
      selection in a lekking moth.
AB  - Male reproductive success in the lesser wax moth Achroia grisella is strongly
      determined by pre-copulatory mate choice, during which females choose among males
      aggregated in small leks based on the attractiveness of ultrasonic songs. Nothing
      is known about the potential of post-copulatory mechanisms to affect male
      reproductive success. However, there is evidence that females at least
      occasionally remate with a second male and that males are unable to produce
      ejaculates quickly after a previous copulation. Here we investigated the effects
      of mating history on ejaculate size and demonstrate that the number of
      transferred sperm significantly decreased from first (i.e., virgin) to second
      (i.e., nonvirgin) copulation within individual males. For males of identical age,
      the number of sperm transferred was higher in virgin than in nonvirgin
      copulations, too, demonstrating that mating history, is responsible for the
      decrease in sperm numbers transferred and not the concomitant age difference.
      Furthermore, the number of transferred sperm was significantly repeatable within
      males. The demonstrated variation in ejaculate size both between subsequent
      copulations as well as among individuals suggests that there is allocation of a
      possibly limited amount of sperm. Because female fecundity is not limited by
      sperm availability in this system, post-copulatory mechanisms, in particular
      sperm competition, may play a previously underappreciated role in the lesser wax
      moth mating system.

PMID- 23531778
TI  - The computational analysis of human testis transcriptome reveals closer ties to
      pluripotency.
AB  - AIMS: The purpose of this study was to identify the differentially expressed
      genes (DEG) in human testis and also evaluate the relationship between human
      testis, human Embryonic Stem Cells (hESC), mouse testis and mouse ESCs (mESC).
      SETTINGS AND DESIGN: It is a prospective analysis designed computationally.
      METHODS AND MATERIAL: The microarray data for human testis, hESCs, mouse testis
      and mESCs were obtained from NCBI-GEO and analyzed for identification of DEGs.
      The results were then compared with mouse testis and extended to ESCs.
      STATISTICAL ANALYSIS USED: Data was analyzed in R using various Bioconductor
      packages. To identify DEGs, 2-fold cut-off and a False Discovery Rate (FDR) below
      0.01 criterions was used. RESULTS: A total 2868 transcripts (DEGs) were found to
      be significantly up-regulated and 2011 transcripts significantly down-regulated
      in human testis compared to other normal tissues. Of the up-regulated
      transcripts, 232 transcripts were grouped as unclassified i.e. had unknown
      annotations at the time of analysis. Gene Ontology (GO) based functional
      annotation of testis specific DEGs indicate that most of the DEGs (~80%) are
      involved in various metabolic processes. Pathway analysis shows over
      representation of Ubiquitin-mediated proteolysis pathway. A core group of 67
      transcripts were found to be common among human testis, mouse testis, hESCs and
      mESCs. CONCLUSIONS: Testis seems to be metabolically very active relative to
      other normal tissues as indicated by functional annotation. The comparison of
      human and mouse testis shows conserved functions and pathways involved in both
      species. Large numbers of genes were found conserved between testis and ESCs
      suggesting very close expression level relationship between reproductive organs
      and complex phenomenon such as dedifferentiation and reprogramming.

PMID- 23531779
TI  - Effects of a large-scale micronutrient powder and young child feeding education
      program on the micronutrient status of children 6-24 months of age in the Kyrgyz
      Republic.
AB  - BACKGROUND/OBJECTIVES: To combat iron and other micronutrient deficiencies, the
      Ministry of Health of the Kyrgyz Republic launched a regional Infant and Young
      Child Nutrition (IYCN) program in 2009, which included promotion of home
      fortification with micronutrient powder (MNP) containing iron (12.5 mg elemental
      iron), vitamin A (300 MUg) and other micronutrients. Every 2 months children aged
      6-24 months were provided 30 sachets to be taken on a flexible schedule. The
      objective was to assess biochemical indicators of iron and vitamin A status among
      children aged 6-24 months at the baseline and follow-up surveys.
      SUBJECTS/METHODS: Cross-sectional representative cluster surveys were conducted
      in 2008 (n=571 children) and 2010 (n=541). Data collected included measurement of
      hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), retinol-binding
      protein, C-reactive protein (CRP) and alpha1-glycoprotein acid (AGP). RESULTS:
      Among all children, declines were observed in the prevalence of: anemia, 50.6%
      versus 43.8% (P=0.05); total iron deficiency (either low ferritin or high sTfR),
      77.3% versus 63.7% (P<0.01); and iron deficiency anemia, 45.5% versus 33.4%
      (P<0.01). Among children without inflammation as measured by CRP and AGP, similar
      declines were observed, but only declines in total iron deficiency and iron
      deficiency anemia reached statistical significance. Among all children and those
      without inflammation, the prevalence of vitamin A deficiency remained the same.
      CONCLUSIONS: One year after the introduction of home fortification with MNP,
      within a larger IYCN program, the prevalence of anemia, iron deficiency and iron
      deficiency anemia declined, but vitamin A deficiency remained unchanged.

PMID- 23531780
TI  - Increased visceral adiposity is associated with coronary artery calcification in
      male patients with chronic kidney disease.
AB  - BACKGROUND/OBJECTIVE: Recent epidemiological data have shown that abdominal fat
      accumulation is associated with increased risk of cardiovascular events in
      patients with chronic kidney disease (CKD). This study aimed to investigate the
      association between visceral adiposity and coronary artery calcification (CAC) in
      CKD patients. SUBJECTS/METHODS: Cross-sectional study with 65 nondialyzed CKD
      male patients (59 +/- 9 years, CKD stages 3 and 4). Abdominal fat compartments
      were assessed by computed tomography (CT) at L4-L5 level. Visceral to
      subcutaneous (V/S) fat ratio was calculated. Visceral obesity was defined as a
      V/S fat ratio greater than the median value of the sample study (>0.55). CAC was
      detected by multi-slice CT. CAC scores were calculated with the Agatston method.
      RESULTS: CAC was present (calcium score >10 AU) in 66% of patients. In the group
      with visceral obesity, the CAC score was significantly higher. This group had
      lower adiponectin and higher leptin levels compared to patients without visceral
      obesity. In the whole sample, higher V/S fat ratio was associated with CAC score,
      independently of age, body mass index, diabetes, ionized calcium, smoking or
      renal function. CONCLUSION: Our results show an association between visceral
      obesity and CAC in CKD patients, suggesting a deleterious effect of visceral fat
      in these patients. Increased visceral adiposity might enhance cardiovascular risk
      in this particular population.

PMID- 23531781
TI  - Trans fatty acids and cardiovascular health: research completed?
AB  - This review asks the question if further research on trans fatty acids and
      cardiovascular health is needed. We therefore review the evidence from human
      studies on trans fatty acids and cardiovascular health, and provide a
      quantitative review of effects of trans fatty acid intake on lipoproteins. The
      results show that the effect of industrially produced trans fatty acids on heart
      health seen in observational studies is larger than predicted from changes in
      lipoprotein concentrations. There is debate on the effect of ruminant trans fatty
      acids and cardiovascular disease. Of special interest is conjugated linoleic acid
      (CLA), which is produced industrially for sale as supplements. Observational
      studies do not show higher risks of cardiovascular disease with higher intakes of
      ruminant trans fatty acids. However, CLA, industrial and ruminant trans fatty
      acids all raise plasma low-density lipoprotein and the total to high-density
      lipoprotein ratio. Gram for gram, all trans fatty acids have largely the same
      effect on blood lipoproteins. In conclusion, the detrimental effects of
      industrial trans fatty acids on heart health are beyond dispute. The exact size
      of effect will remain hard to determine. Further research is warranted on the
      effects of ruminant trans fatty acids and CLA on cardiovascular disease and its
      risk factors.

PMID- 23531782
TI  - Refeeding syndrome in children with different clinical aetiology.
AB  - Refeeding syndrome (RFS) is a well-described state of the series of metabolic and
      biochemical changes that can occur during the feeding of malnourished persons.
      The shifts in fluids and electrolytes can lead to complications during artificial
      feeding, which if not recognised and untreated can lead to death. Although the
      physiology and pathophysiology of RFS is well known, the circumstances under
      which the RFS appears, clinical manifestations and management of these patients
      are less clear. There are few published studies describing the occurrence of RFS
      in children. We describe two cases of RFS in children. The first case is a boy
      with unrecognised coeliac disease and second case is a girl with cerebral palsy.
      In both cases, the RFS has developed without clinical symptoms and it was shown
      only through laboratory findings. Electrolyte disturbances have been successfully
      corrected and treatment of the underlying disease continued. 

PMID- 23531783
TI  - Temperature and time dependence on ZnS microstructure and phases obtained through
      hydrothermal decomposition of diethyldithiocarbamate complexes.
AB  - Zinc sulphide was obtained through hydrothermal decomposition of [Zn(S2CNEt2)]
      under different experimental conditions such as temperatures and reaction times.
      Hydrothermal reactions were carried out in a stainless steel autoclave at 160,
      180 and 200  degrees C for 3, 6 and 24 hours. The obtained products were
      characterized using X-ray diffraction, scanning and high resolution transmission
      electron microscopies. Particle size and microstrain were determined by Rietveld
      refinement of experimental X-ray diffraction patterns. The obtained crystal size
      values were in the range of 6.1 to 30 nm and as the temperature and reaction
      times increase the particle size also increases. Band gap values are in the range
      of 3.34 to 3.60 eV and are highly dependent on the crystal microstrain. The
      catalyst activities were studied through the degradation of methylene blue dye
      solutions under ultraviolet radiation.

PMID- 23531784
TI  - Iatrogenic giant cell tumor at bone graft harvesting site.
AB  - 30 year old female patient with giant cell tumor of the distal tibia initially
      treated at a peripheral nononcological center by curettage and autologous bone
      grafting from the ipsilateral iliac crest reported to us with local recurrence
      and an implantation giant cell tumor at the graft harvesting site which required
      extensive surgeries at both sites. The risk of iatrogenic direct implantation of
      tumor, often attributable to inadequate surgical planning or poor surgical
      techniques, and the steps to prevent such complication is reported here.

PMID- 23531785
TI  - Adaptations in tibial cortical thickness and total volumetric bone density in
      postmenopausal South Asian women with small bone size.
AB  - There is some evidence that South Asian women may have an increased risk of
      osteoporosis compared with Caucasian women, although whether South Asians are at
      increased risk of fracture is not clear. It is unknown whether older South Asian
      women differ from Caucasian women in bone geometry. This is the first study, to
      the authors' knowledge, to use peripheral Quantitative Computed Tomography (pQCT)
      to measure radial and tibial bone geometry in postmenopausal South Asian women.
      In comparison to Caucasian women, Asian women had smaller bone size at the 4% (
      18% p<0.001) and 66% radius (-15% p=0.04) as well as increased total density at
      the 4% (+13% p=0.01) radius. For the tibia, they had a smaller bone size at the
      4% (-16% p=0.005) and 14% (-38% p=0.002) sites. Also, Asians had increased
      cortical thickness (-17% p=0.04) at the 38% tibia, (in proportion to bone size (
      30% p=0.003)). Furthermore, at the 4% and 14% tibia there were increased total
      densities (+12% to +29% p<0.01) and at the 14% tibia there was increased cortical
      density (+5% p=0.005) in Asians. These differences at the 14% and 38% (but not
      4%) remained statistically significant after adjustment for Body Mass Index
      (BMI). These adaptations are similar to those seen previously in Chinese women.
      Asian women had reduced strength at the radius and tibia, evidenced by the 20-40%
      reduction in both polar Strength Strain Index (SSIp) and fracture load (under
      bending). Overall, the smaller bone size in South Asians is likely to be
      detrimental to bone strength, despite some adaptations in tibial cortical
      thickness and tibial and radial density which may partially compensate for this.

PMID- 23531786
TI  - Melatonin modulates baroreflex control via area postrema.
AB  - Pineal gland and its hormone melatonin have been implicated in modulation of
      cardiovascular system. We aimed at studying the effects of melatonin on
      baroreflex sensitivity and the role of area postrema, as a component modulator of
      baroreflex arch. Mean arterial pressure (MAP) and heart rate (HR) were recorded
      in conscious freely moving rats. Baroreceptor reflex sensitivity was assessed by
      determining the HR responses to ramped infusions of phenylephrine (PE) and sodium
      nitroprusside (SNP)-induced MAP changes. Melatonin bolus (0.11 mg/kg) immediately
      followed by its continuous infusion (0.43 * 10(-9) mol/L at a rate of 0.65 mL/h
      for 30 min) in healthy normotensive rats produced a downward shift of
      baroreceptor reflex control with a substantial inhibition of reflex tachycardia (
      32%) and potentiation of reflex bradycardia (+20%). Ablation of area postrema
      (APX group) induced a sustained decrease of MAP (101 +/- 3 vs. 116 +/- 3 mmHg, P
      < 0.05 in comparison with sham rats, respectively). The melatonin-induced
      alterations of baroreflex function observed in the sham group were abolished in
      the APX group. We conclude that circulating melatonin can modulate baroreceptor
      reflex control of HR, thus resetting it toward lower HR values. The modulatory
      effects of melatonin may be mediated via melatonin receptors in the area
      postrema, located outside the blood-brain barrier.

PMID- 23531787
TI  - EDGE-pro: Estimated Degree of Gene Expression in Prokaryotic Genomes.
AB  - BACKGROUND: The expression levels of bacterial genes can be measured directly
      using next-generation sequencing (NGS) methods, offering much greater sensitivity
      and accuracy than earlier, microarray-based methods. Most bioinformatics software
      for estimating levels of gene expression from NGS data has been designed for
      eukaryotic genomes, with algorithms focusing particularly on detection of
      splicing patterns. These methods do not perform well on bacterial genomes.
      RESULTS: Here we describe the first software system designed explicitly for
      quantifying the degree of gene expression in bacteria and other prokaryotes. EDGE
      pro (Estimated Degree of Gene Expression in PROkaryotes) processes the raw data
      from an RNA-seq experiment on a bacterial or archaeal species and produces
      estimates of the expression levels for each gene in these gene-dense genomes.
      SOFTWARE: The EDGE-pro tool is implemented as a pipeline of C++ and Perl programs
      and is freely available as open-source code at
      http://www.genomics.jhu.edu/software/EDGE/index.shtml.

PMID- 23531788
TI  - Observing fermionic statistics with photons in arbitrary processes.
AB  - Quantum mechanics defines two classes of particles-bosons and fermions-whose
      exchange statistics fundamentally dictate quantum dynamics. Here we develop a
      scheme that uses entanglement to directly observe the correlated detection
      statistics of any number of fermions in any physical process. This approach
      relies on sending each of the entangled particles through identical copies of the
      process and by controlling a single phase parameter in the entangled state, the
      correlated detection statistics can be continuously tuned between bosonic and
      fermionic statistics. We implement this scheme via two entangled photons shared
      across the polarisation modes of a single photonic chip to directly mimic the
      fermion, boson and intermediate behaviour of two-particles undergoing a
      continuous time quantum walk. The ability to simulate fermions with photons is
      likely to have applications for verifying boson scattering and for observing
      particle correlations in analogue simulation using any physical platform that can
      prepare the entangled state prescribed here.

PMID- 23531790
TI  - Sex-related differences in mast cell activity and doxorubicin toxicity: a study
      in spontaneously hypertensive rats.
AB  - Clinically, girls appear to be more sensitive than boys to the cardiotoxic
      effects of doxorubicin, whereas the opposite may be true for adults. To identify
      and characterize potential sex-related differences, adult male and female
      spontaneously hypertensive rats (SHR; some ovariectomized [OVX]) received 1 mg/kg
      of doxorubicin or saline iv weekly for 9, 10, or 12 weeks. Weight gain was slower
      in treated males. Serum concentrations of cholesterol and triglycerides increased
      and those of albumin decreased in both sexes, but changes were more pronounced in
      treated males. Treated males had significantly more severe cardiomyopathy scores
      and higher serum levels of cTnT than females. The increased cardiotoxicity was
      accompanied by higher numbers of cardiac mast cells (MCs) and percentage of
      cardiac MCs undergoing degranulation. Doxorubicin-treated OVX animals had
      significantly increased numbers of cardiac MCs, more severe myocardial lesions,
      and elevated serum concentrations of cTnT compared to doxorubicin-treated normal
      female SHR. The severity of cardiac lesions in the OVX female was similar to that
      observed in doxorubicin-treated males. This study demonstrated the presence of
      sex-related differences in the cardiotoxic effects elicited by doxorubicin and
      identified variations in the level of cardiac MC activity as a factor which could
      possibly contribute to the male-female dissimilarity. 

PMID- 23531791
TI  - Comparison of cardiac troponin I and T, including the evaluation of an
      ultrasensitive assay, as indicators of doxorubicin-induced cardiotoxicity.
AB  - Cardiac troponin (cTn) has been utilized to assess acute myocardial injury, but
      the cTn response in active/ongoing chronic injury is not well documented. The
      purpose of this study was to characterize the cardiac troponin I (cTnI), cardiac
      troponin T (cTnT), high-sensitivity cTnI, hematology, and clinical chemistry
      responses in rats treated with doxorubicin. Rats treated with 1, 2, or 3
      mg/kg/week (wk) of doxorubicin for 2, 4, or 6 wks were sacrificed after 0, 2, or
      4 wks of recovery and compared to untreated controls and animals treated with
      doxorubicin/dexrazoxane (50 mg/kg/wk) or etoposide (1 and 3 mg/kg/wk). The
      incidence and mean magnitude of cTn response increased with increasing dose
      and/or duration of doxorubicin treatment. Conversely, dexrazoxane/doxorubicin was
      partially protective for cardiotoxicity, and minimal cardiotoxicity occurred with
      etoposide treatment. Both cTnI and cTnT effectively identified doxorubicin
      induced injury as indicated by vacuolation of cardiomyocytes of the
      atria/ventricles. The association between the cTn responses and histological
      changes was greater at the higher total exposures, but the magnitude of cTn
      response did not match closely with histologic grade. The high-sensitivity cTnI
      assay was also effective in identifying cardiac injury. Alterations occurred in
      the hematology and clinical chemistry parameters and reflected both dose and
      duration of doxorubicin treatment. 

PMID- 23531792
TI  - Different pathways of constitutive androstane receptor-mediated liver hypertrophy
      and hepatocarcinogenesis in mice treated with piperonyl butoxide or
      decabromodiphenyl ether.
AB  - The constitutive androstane receptor (CAR) is essential for Cyp2b induction,
      liver hypertrophy, and hepatocarcinogenesis in response to phenobarbital (PB).
      Liver hypertrophy with Cyp2b induction is a major mode of action of
      hepatocarcinogenesis in rodents. However, it remains unclear whether CAR is
      involved in the response to many other nongenotoxic hepatocarcinogens besides PB.
      In this study, we investigated CAR involvement in liver hypertrophy and
      hepatocarcinogenesis of Cyp2b-inducing nongenotoxic hepatocarcinogens, piperonyl
      butoxide (PBO), and decabromodiphenyl ether (DBDE), using wild-type and CAR
      knockout (CARKO) male mice. PB was used as the positive control. In the wild-type
      mice, 4-week treatment with PBO, DBDE, or PB induced hepatocellular hypertrophy
      with increased Cyp2b10 messenger RNA and Cyp2b protein expression. In CARKO mice,
      only PBO showed liver hypertrophy with Cyp2b10 and Cyp3a11 induction. After 27
      week treatment following diethylnitrosamine initiation, PBO and PB generated many
      eosinophilic altered foci/adenomas in wild-type mice; however, the lesions were
      far less frequent in CARKO mice. DBDE increased the multiplicity of basophilic
      altered foci/adenomas in wild-type and CARKO mice. Our findings indicate that
      murine CAR plays major roles in hepatocarcinogenesis but not in liver hypertrophy
      of PBO. DBDE may act via CAR-independent pathways during hepatocarcinogenesis. 

PMID- 23531793
TI  - Society of Toxicologic Pathology position paper on best practices on recovery
      studies: the role of the anatomic pathologist.
AB  - This article reviews the regulatory guidelines that provide for the inclusion of
      recovery groups in toxicology studies, presents the challenges in the design and
      interpretation of nonclinical recovery studies, and summarizes the best practices
      for the role of an anatomic pathologist regarding toxicology studies with
      recovery groups. Evaluating the potential recovery of histopathologic findings
      induced by a biopharmaceutical requires the active participation of one or more
      anatomic pathologists. Their expertise is critical in risk assessment regarding
      the potential for recovery as well as providing scientific guidance in the design
      and evaluation of studies with recovery groups. 

PMID- 23531789
TI  - Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds.
AB  - Seasonally breeding birds detect environmental signals, such as light,
      temperature, food availability, and presence of mates to time reproduction.
      Hypothalamic neurons integrate external and internal signals, and regulate
      reproduction by releasing neurohormones to the pituitary gland. The pituitary
      gland synthesizes and releases gonadotropins which in turn act on the gonads to
      stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin
      secretion is controlled by the hypothalamus is key to our understanding of the
      mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin
      releasing hormone (GnRH), activates reproduction by stimulating gonadotropin
      synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory
      hormone (GnIH), inhibits gonadotropin synthesis and release directly by acting on
      the pituitary gland or indirectly by decreasing the activity of GnRH neurons.
      Therefore, the next step to understand seasonal reproduction is to investigate
      how the activities of GnRH and GnIH neurons in the hypothalamus and their
      receptors in the pituitary gland are regulated by external and internal signals.
      It is possible that locally-produced triiodothyronine resulting from the action
      of type 2 iodothyronine deiodinase on thyroxine stimulates the release of
      gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is
      also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone,
      stimulates the synthesis and release of GnIH and GnIH may therefore regulate a
      daily rhythm of gonadotropin secretion. GnIH may also temporally suppress
      gonadotropin secretion when environmental conditions are unfavorable.
      Environmental and social milieus fluctuate seasonally in the wild. Accordingly,
      complex interactions of various neuronal and hormonal systems need to be
      considered if we are to understand the mechanisms underlying seasonal
      reproduction.

PMID- 23531794
TI  - Complex histopathologic response in rat kidney to oral beta-myrcene: an unusual
      dose-related nephrosis and low-dose alpha2u-globulin nephropathy.
AB  - Oral gavage studies with beta-myrcene in male F344 rats showed a complex renal
      pathology comprising both alpha2u-globulin (alpha2u-g) nephropathy, an unusual
      nephrosis involving the outer stripe of outer medulla (OSOM), and an increased
      incidence of renal tubule tumors by 2 years. In the 90-day and 2-year studies,
      respectively, alpha2u-g nephropathy and linear papillary mineralization were
      observed in males at the two lower doses but were absent from the high dose.
      Nephrosis was characterized by dilation of the S3 tubules, nuclear enlargement
      (including karyomegaly), and luminal pyknotic cells, all in the outermost OSOM.
      Nephrosis was minimal at the higher doses in the 90-day study, but progressed to
      a severe grade in males dosed with 1,000 mg/kg for 2 years. Renal tubule tumors
      developed in treated groups with incidences up to 30% in the 250 and 500 mg/kg
      male dose groups. Tumors at the lower doses in males may have been associated
      with alpha2u-g nephropathy, while those at higher doses in both sexes may have
      been due to the nephrosis. Because beta-myrcene induced a complex spectrum of
      renal pathology, the alpha2u-g nephropathy mechanism cannot be the sole mechanism
      of carcinogenesis in these rats. 

PMID- 23531795
TI  - The placenta in toxicology. Part III: Pathologic assessment of the placenta.
AB  - This short review is derived from the peer-reviewed literature and the experience
      and case materials of the authors. Brief illustrated summaries are presented on
      the gross and histologic normal anatomy of rodent and macaque placentas,
      including typical organ weights, with comments on differences from the human
      placenta. Common incidental findings, background lesions, and induced toxic
      lesions are addressed, and a recommended strategy for pathologic evaluation of
      placentas is provided. 

PMID- 23531796
TI  - The placenta in toxicology. Part II: Systemic and local immune adaptations in
      pregnancy.
AB  - During pregnancy, the maternal immune system is challenged by the semiallogeneic
      fetus, which must be tolerated without compromising fetal or maternal health.
      This review updates the systemic and local immune changes taking place during
      human pregnancy, including some examples in rodents. Systemic changes are induced
      by contact of maternal blood with placental factors and include enhanced innate
      immunity with increased activation of granulocytes and nonclassical monocytes.
      Although a bias toward T helper (Th2) and regulatory T cell (Treg) immunity has
      been associated with healthy pregnancy, the relationship between different
      circulating Th cell subsets is not straightforward. Instead, these adaptations
      appear most evidently at the fetal-maternal interface, where for instance Tregs
      are enriched and promote fetal tolerance. Also innate immune cells, that is,
      natural killer cells and macrophages, are enriched, constituting the majority of
      decidual leukocytes. These cells not only contribute to immune regulation but
      also aid in establishing the placenta by promoting trophoblast recruitment and
      angiogenesis. Thus, proper interaction between leukocytes and placental
      trophoblasts is necessary for normal placentation and immune adaptation.
      Consequently, spontaneous maladaptation or interference of the immune system with
      toxic substances may be important contributing factors for the development of
      pregnancy complications such as preeclampsia, preterm labor, and recurrent
      miscarriages. 

PMID- 23531802
TI  - Emotional tears facilitate the recognition of sadness and the perceived need for
      social support.
AB  - The tearing effect refers to the relevance of tears as an important visual cue
      adding meaning to human facial expression. However, little is known about how
      people process these visual cues and their mediating role in terms of emotion
      perception and person judgment. We therefore conducted two experiments in which
      we measured the influence of tears on the identification of sadness and the
      perceived need for social support at an early perceptional level. In two
      experiments (1 and 2), participants were exposed to sad and neutral faces. In
      both experiments, the face stimuli were presented for 50 milliseconds. In
      experiment 1, tears were digitally added to sad faces in one condition.
      Participants demonstrated a significant faster recognition of sad faces with
      tears compared to those without tears. In experiment 2, tears were added to
      neutral faces as well. Participants had to indicate to what extent the displayed
      individuals were in need of social support. Study participants reported a greater
      perceived need for social support to both sad and neutral faces with tears than
      to those without tears. This study thus demonstrated that emotional tears serve
      as important visual cues at an early (pre-attentive) level.

PMID- 23531803
TI  - Was that cheating? Perceptions vary by sex, attachment anxiety, and behavior.
AB  - We generated an inventory of 27 interpersonal behaviors and examined the extent
      to which participants judged each behavior as cheating on a long-term partner. We
      predicted variation in these judgments based on participant sex and attachment
      insecurity. Ratings for items ranged considerably; participants rated sexual
      behaviors as most indicative of cheating, then erotic behaviors, followed by
      behaviors consistent with a romantic relationship, and then behaviors related to
      financial support. Women rated ten items higher than did men, and men's ratings
      were higher on a minor financial support item. Higher attachment anxiety was
      associated with higher ratings for 18 of 27 behaviors; higher attachment
      avoidance was associated with lower scores on five items and higher scores on one
      item. Principle Axis Factoring identified three dimensions; sexual interaction,
      behaviors indicating close relationships, and casual social interaction. We
      discuss these results using the framework of attachment theory and sex-specific
      mating strategies.

PMID- 23531804
TI  - Quick and dirty: some psychosocial costs associated with the Dark Triad in three
      countries.
AB  - The current study provides the first examination of the relationship between life
      history indicators and the Dark Triad traits in an international sample drawn
      from the U.S. (n = 264), Singapore (n = 185), and Poland (n = 177). In all three
      samples, the Dark Triad traits were associated with psychosocial costs, although
      there were more links in the Singaporean and Polish samples than in the American
      sample. In the U.S., the quality of one's romantic relationships and psychopathy
      were negatively correlated. Narcissism was higher in the Polish and American
      samples than in the Singaporean sample. Men scored higher than women did
      regardless of location and the sex difference in the individual differences in
      life histories was mediated by the Dark Triad composite. Results suggest the Dark
      Triad are related to a volatile socioecology composed of psychosocial costs in
      the familial, romantic, and platonic relationships.

PMID- 23531805
TI  - Who punishes? Personality traits predict individual variation in punitive
      sentiment.
AB  - Cross-culturally, participants in public goods games reward participants and
      punish defectors to a degree beyond that warranted by rational, profit-maximizing
      considerations. Costly punishment, where individuals impose costs on defectors at
      a cost to themselves, is thought to promote the maintenance of cooperation.
      However, despite substantial variation in the extent to which people punish,
      little is known about why some individuals, and not others, choose to pay these
      costs. Here, we test whether personality traits might contribute to variation in
      helping and punishment behavior. We first replicate a previous study using public
      goods scenarios to investigate effects of sex, relatedness and likelihood of
      future interaction on willingness to help a group member or to punish a
      transgressor. As in the previous study, we find that individuals are more willing
      to help related than unrelated needy others and that women are more likely to
      express desire to help than men. Desire to help was higher if the probability of
      future interaction is high, at least among women. In contrast, among these
      variables, only participant sex predicted some measures of punitive sentiment.
      Extending the replication, we found that punitive sentiment, but not willingness
      to help, was predicted by personality traits. Most notably, participants scoring
      lower on Agreeableness expressed more anger towards and greater desire to punish
      a transgressor, and were more willing to engage in costly punishment, at least in
      our scenario. Our results suggest that some personality traits may contribute to
      underpinning individual variation in social enforcement of cooperation.

PMID- 23531806
TI  - Laughing at the looking glass: does humor style serve as an interpersonal signal?
AB  - OBJECTIVE: The provision of information appears to be an important feature of
      humor. The present studies examined whether humor serves as an interpersonal
      signal such that an individual's style of humor is associated with how the
      individual is perceived by others. METHOD: We examined this issue across two
      studies. In Study 1, undergraduate participants (257 targets) were rated more
      positively by their friends and family members (1194 perceivers) when they
      possessed more benign humor styles. In Study 2, 1190 community participants rated
      the romantic desirability of targets ostensibly possessing different humor
      styles. RESULTS: Across both studies, our results were consistent with the
      possibility that humor serves as a signal. More specifically, individuals with
      benign humor styles (affiliative and self-enhancing humor styles) were evaluated
      more positively than those targets with injurious humor styles (aggressive and
      self-defeating humor styles). CONCLUSION: These findings are discussed in terms
      of the role that humor may play in interpersonal perception and relationships.

PMID- 23531807
TI  - Facial visualizations of women's voices suggest a cross-modality preference for
      femininity.
AB  - Women with higher-pitched voices and more feminine facial features are commonly
      judged as being more attractive than are women with lower-pitched voices and less
      feminine faces, possibly because both features are affected by (age-related)
      variations in endocrine status. These results are primarily derived from
      investigations of perceptions of variations in single-modality stimuli (i.e.,
      faces or voices) in samples of young adult women. In the present study we sought
      to test whether male and female perceptions of women's voices affect visual
      representations of facial femininity. Eighty men and women judged voice
      recordings of 10 young girls (11-15 years), 10 adult women (19-28 years) and 10
      peri-/post-menopausal women (50-64 years) on age, attractiveness, and femininity.
      Another 80 men and women were asked to indicate the face they think each voice
      corresponded to using a video that gradually changed from a masculine looking
      male face into a feminine looking female face. Both male and female participants
      perceived voices of young girls and adult women to be significantly younger, more
      attractive and feminine than those of peri-/post-menopausal women. Hearing young
      girls' and adult women's voices resulted in both men and women selecting faces
      that differed markedly in apparent femininity from those associated with peri
      /post-menopausal women's voices. Voices of young girls had the strongest effect
      on visualizations of facial femininity. Our results suggest a cross-modal
      preference for women's vocal and facial femininity, which depends on female age
      and is independent of the perceiver's sex.

PMID- 23531809
TI  - Sexual whodunits and evolutionary psychology: the shaping of three novels.

PMID- 23531810
TI  - Female attraction to appetitive-aggressive men is modulated by women's menstrual
      cycle and men's vulnerability to traumatic stress.
AB  - Many studies have reported that during high fertility points in the menstrual
      cycle, women demonstrate increased preference for men with masculinized faces and
      bodies. In this study, we analyzed whether appetitive aggression in men serves as
      an additional signal for a favored partner choice. Appetitive aggression
      describes the intrinsic motivation to act violently even when not being
      threatened. This study evaluated the responses of 1212 women to one of four
      descriptions regarding a soldier's experience after returning from war. The four
      vignettes included trauma related symptoms with high or low appetitive
      aggression, or no trauma related symptoms with high or low appetitive aggression.
      Participants rated their desirability for the soldier in regards to potential
      long-term and short-term relationships. Results indicate that women preferred a
      soldier high in appetitive aggression as a short-term mate but not as a long-term
      relationship. This preference for the "warrior" was higher for women in their
      fertile window of the menstrual cycle. We conclude that women in their fertile
      window prefer men exhibiting higher appetitive aggression as a short-term
      partner, revealing appetitive aggression in men may serve as a signal for a
      higher genetic fitness.

PMID- 23531812
TI  - Looming detection by identified visual interneurons during larval development of
      the locust Locusta migratoria.
AB  - Insect larvae clearly react to visual stimuli, but the ability of any visual
      neuron in a newly hatched insect to respond selectively to particular stimuli has
      not been directly tested. We characterised a pair of neurons in locust larvae
      that have been extensively studied in adults, where they are known to respond
      selectively to objects approaching on a collision course: the lobula giant motion
      detector (LGMD) and its postsynaptic partner, the descending contralateral motion
      detector (DCMD). Our physiological recordings of DCMD axon spikes reveal that at
      the time of hatching, the neurons already respond selectively to objects
      approaching the locust and they discriminate between stimulus approach speeds
      with differences in spike frequency. For a particular approaching stimulus, both
      the number and peak frequency of spikes increase with instar. In contrast, the
      number of spikes in responses to receding stimuli decreases with instar, so
      performance in discriminating approaching from receding stimuli improves as the
      locust goes through successive moults. In all instars, visual movement over one
      part of the visual field suppresses a response to movement over another part.
      Electron microscopy demonstrates that the anatomical substrate for the selective
      response to approaching stimuli is present in all larval instars: small neuronal
      processes carrying information from the eye make synapses both onto LGMD
      dendrites and with each other, providing pathways for lateral inhibition that
      shape selectivity for approaching objects.

PMID- 23531813
TI  - Hypoxia-induced compression in the tracheal system of the tobacco hornworm
      caterpillar, Manduca sexta.
AB  - Abdominal pumping in caterpillars has only been documented during molting. Using
      synchrotron X-ray imaging in conjunction with high-speed flow-through
      respirometry, we show that Manduca sexta caterpillars cyclically contract their
      bodies in response to hypoxia, resulting in significant compressions of the
      tracheal system. Compression of tracheae induced by abdominal pumping drives
      external gas exchange, as evidenced by the high correlation between CO2 emission
      peaks and body movements. During abdominal pumping, both the compression
      frequency and fractional change in diameter of tracheae increased with body mass.
      However, abdominal pumping and tracheal compression were only observed in larger,
      older caterpillars (>0.2 g body mass), suggesting that this hypoxic response
      increases during ontogeny. The diameters of major tracheae in the thorax
      increased isometrically with body mass. However, tracheae in the head did not
      scale with mass, suggesting that there is a large safety margin for oxygen
      delivery in the head in the youngest animals. Together, these results highlight
      the need for more studies of tracheal system scaling and suggest that patterns of
      tracheal investment vary regionally in the body.

PMID- 23531814
TI  - Gait transitions and modular organization of mammal locomotion.
AB  - Quadrupedal locomotion is the result of complex interactions between
      biomechanical and neural systems. During steady gaits, both systems are in stable
      states. When the animal changes its speed, transitions between gaits can occur in
      which the different coordination parameters are dissociated. Consequently,
      transitions are the periods where it is possible to detect and identify those
      parameters involved in the mechanical or neural control of locomotion. We studied
      interlimb coordination using a sequential method (antero-posterior sequence) to
      measure the footfall patterns of dogs when accelerating and decelerating from 1.5
      m s(-1) to more than 6 m s(-1) and back. We obtained 383 transitions between all
      the symmetrical and asymmetrical gaits used by the dogs. Analysis of the
      interlimb coordination modifications and of each foot parameter showed that
      mechanics drive the stance phase whereas coordination is controlled during the
      swing phase. Furthermore, comparison of the transition patterns between all gaits
      reveals the modular organization of locomotion: a pectoral module coordinates the
      two forelimbs, a pelvic module coordinates the two hindlimbs and an axial module
      coordinates the two pairs of limbs and the trunk motion. The three modules
      cooperate to give rise to a template of stable interlimb coordination pattern,
      such as walk, trot or gallop.

PMID- 23531815
TI  - The effects of hibernation on the contractile and biochemical properties of
      skeletal muscles in the thirteen-lined ground squirrel, Ictidomys
      tridecemlineatus.
AB  - Hibernation is a crucial strategy of winter survival used by many mammals. During
      hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle
      through a series of torpor bouts, each lasting more than a week, during which the
      animals are largely immobile. Previous hibernation studies have demonstrated that
      such natural models of skeletal muscle disuse cause limited or no change in
      either skeletal muscle size or contractile performance. However, work loop
      analysis of skeletal muscle, which provides a realistic assessment of in vivo
      power output, has not previously been undertaken in mammals that undergo
      prolonged torpor during hibernation. In the present study, our aim was to assess
      the effects of 3 months of hibernation on contractile performance (using the work
      loop technique) and several biochemical properties that may affect performance.
      There was no significant difference in soleus muscle power output-cycle frequency
      curves between winter (torpid) and summer (active) animals. Total antioxidant
      capacity of gastrocnemius muscle was 156% higher in torpid than in summer
      animals, suggesting one potential mechanism for maintenance of acute muscle
      performance. Soleus muscle fatigue resistance was significantly lower in torpid
      than in summer animals. Gastrocnemius muscle glycogen content was unchanged.
      However, state 3 and state 4 mitochondrial respiration rates were significantly
      suppressed, by 59% and 44%, respectively, in mixed hindlimb skeletal muscle from
      torpid animals compared with summer controls. These findings in hindlimb skeletal
      muscles suggest that, although maximal contractile power output is maintained in
      torpor, there is both suppression of ATP production capacity and reduced fatigue
      resistance. 

PMID- 23531816
TI  - Rhythmic profiles of cell cycle and circadian clock gene transcripts in mice: a
      possible association between two periodic systems.
AB  - The circadian system shapes the rhythms of most biological functions. The
      regulation of the cell cycle by a circadian clock was suggested to operate via
      stages S, G2 and G2/M. This study investigated a possible time link at stages G1
      and G1/S as well. The daily expression profiles of cell cycle markers (Ccnd1,
      Ccne1 and Pcna) and circadian clock genes (Per2 and Clock) were monitored in
      liver and esophagus (low and high proliferation index, respectively) of BALB/c
      mice. Locomotor activity displayed a 24 h rhythm, establishing the circadian
      organization of the suprachiasmatic nucleus. In the liver, the mRNA level of Per2
      and Clock fitted the circadian rhythm with a 7.5 h shift. This temporal pattern
      suggests that the liver harbors a functional circadian clock. The rhythm of the
      analyzed cell cycle genes, however, was of low significance fitness and showed an
      opposite peak time between Pcna and Clock. These results indicate a weak
      regulatory role of the circadian clock. In the esophagus, the rhythms of Clock
      and Per2 mRNA had a similar peak time and non-circadian periods. These results
      suggest either that the esophagus does not harbor a functional circadian
      apparatus or that the phenotypes stem from differences in phase and amplitude of
      the rhythms of its various cell types. The similarity in the rhythm parameters of
      Clock, Ccne1 and Pcna transcripts questions the control of the circadian clock on
      the cell cycle along the G1 and G1/S stages. Yet the G1/S transition may play a
      role in modulating the local clock of proliferating tissues.

PMID- 23531817
TI  - Immune response to an endotoxin challenge involves multiple immune parameters and
      is consistent among the annual-cycle stages of a free-living temperate zone bird.
AB  - Trade-offs between immune function and other physiological and behavioural
      processes are central in ecoimmunology, but one important problem is how to
      distinguish a reallocation of resources away from the immune system from a
      reallocation or redistribution within the immune system. While variation in
      baseline values of individual immune parameters is well established, studies in
      wild animals on multiple parameters during an immune response are lacking. It
      also remains to be tested whether and how immune responses correlate with
      baseline values that vary, for example, over the course of an annual cycle. We
      studied immunological responses to an endotoxin challenge in skylarks (Alauda
      arvensis), a partial migrant bird breeding in temperate zones. We compared birds
      injected with the endotoxin LPS with un-injected controls, characterizing
      immunological responses with leukocyte profiles, titres of lytic enzymes and
      natural antibodies, and concentrations of haptoglobin and heat shock proteins. We
      did this in five annual-cycle stages to test whether the response varied
      throughout the year. The endotoxin challenge affected six of 10 measured
      parameters. Lysis titres and proportions of heterophils increased; haptoglobin
      concentrations and proportions of lymphocytes, basophils and eosinophils
      decreased. The variable effects on different immune components demonstrate the
      complexity of an immune response. We found no evidence that the response differed
      between annual-cycle stages. The response was independent of baseline measures
      taken directly upon capture in the field, indicating that birds were facing no
      immunological ceiling when mounting an immune response. Values of five parameters
      collected under field conditions were significantly related to values taken under
      standardized laboratory conditions. We conclude that multiple parts of the immune
      system are modulated during an immunological response and that responses are not
      re-organized throughout the annual cycle. 

PMID- 23531818
TI  - The effects of elevated temperature on the sexual traits, immunology and
      survivorship of a tropical ectotherm.
AB  - In 2007, the Intergovernmental Panel on Climate Change projected an average
      global air temperature increase of 1.1-6.4 degrees C by the end of the 21st
      century. Although the tropics are predicted to experience less extreme
      temperature increases than regions of higher latitude, tropical ectotherms live
      close to their thermal limits, and are thus particularly vulnerable to increases
      in temperature. In this study, we examined how predicted patterns of global
      warming will affect survival and sexual traits in the Trinidadian guppy (Poecilia
      reticulata). Guppies were exposed from birth to one of four temperature
      treatments: 23, 25 (control), 28 or 30 degrees C. We measured brood survival and,
      at sexual maturity, male ornamentation, sperm traits and immune response. Our
      results show that increases in temperature result in guppies that have shorter,
      slower sperm but that there is an optimum temperature for ornamental hue at 28
      degrees C. Given the importance of sperm quality for reproduction, these results
      suggest population viability could be affected by warming. However, we found no
      difference in brood survival or immune response to a novel antigen across the
      treatments, indicating that survival may not be as vulnerable as previously
      thought. Overall, our data suggest that male sexual traits, and in particular
      sperm performance, are more sensitive than survival to a warming environment. 

PMID- 23531819
TI  - Identification and characterisation of a functional aquaporin water channel
      (Anomala cuprea DRIP) in a coleopteran insect.
AB  - Water transport across the plasma membrane depends on the presence of the water
      channel aquaporin (AQP), which mediates the bulk movement of water through
      osmotic and pressure gradients. In terrestrial insects, which are solid and/or
      plant feeders, the entrance and exit of water is primarily executed along the
      alimentary tract, where the hindgut, particularly the rectum, is the major site
      of water conservation. A cDNA encoding the homologue of the water-specific
      Drosophila AQP [Drosophila integral protein (DRIP)] was identified through the RT
      PCR of RNA isolated from the rectum of the cupreous chafer larvae, Anomala
      cuprea, a humus and plant root feeder. This gene (Anocu AQP1) has a predicted
      molecular mass of 26.471 kDa, similar to the DRIP clade of insect AQPs
      characterised from caterpillars, flies and several liquid-feeding insects. When
      expressed in Xenopus laevis oocytes, Anocu AQP1 showed the hallmarks of aquaporin
      mediated water transport but no glycerol or urea permeability, and the reversible
      inhibition of elevated water transport through 1 mmol l(-1) HgCl2. This is the
      first experimental demonstration of the presence of a water-specific AQP, namely
      DRIP, in the Coleoptera. The genome of the model beetle Tribolium castaneum
      contains six putative AQP sequences, one of which (Trica-1a, XP_972862) showed
      the highest similarity to Anocu AQP1 (~60% amino acid identity). Anocu AQP1 is
      predominantly expressed in the rectum. Using a specific antibody raised against
      DRIP in the silkworm Bombyx mori (AQP-Bom1), Anocu AQP1 was localised to the
      apical plasma membrane of rectal epithelial cells, and lacking in the midgut and
      gastric caecal epithelia. Based on the BeetleBase prediction, there are three
      putative AQPs (Trica-3a, 3b, 3c: XP_970728, 970912, 970791) that are homologous
      to B. mori aquaglyceroporin [AQP-Bom2 (GLP)]. The immunocytochemical studies
      using the specific anti-peptide antibody against AQP-Bom2 revealed the presence
      of the GLP homologue at the apical plasma membrane of enterocytes in the midgut
      and gastric caeca. Thus, DRIP (Anocu AQP1) and the putative GLP share epithelial
      fluid-transporting roles along the alimentary tract in cupreous chafer larvae. 

PMID- 23531820
TI  - Flight performance of western sandpipers, Calidris mauri, remains uncompromised
      when mounting an acute phase immune response.
AB  - Migratory birds have been implicated in the spread of some zoonotic diseases, but
      how well infected individuals can fly remains poorly understood. We used western
      sandpipers, Calidris mauri, to experimentally test whether flight is affected
      when long-distance migrants are mounting an immune response and whether migrants
      maintain immune defences during a flight in a wind tunnel. We measured five
      indicators of innate immunity in 'flown-healthy' birds (flying in a wind tunnel
      without mounting an immune response), 'flown-sick' birds (flying while mounting
      an acute phase response, which is part of induced innate immunity), and a non
      flying control group ('not-flown'). Voluntary flight duration did not differ
      between flown-healthy and flown-sick birds, indicating that mounting an acute
      phase response to simulated infection did not hamper an individual's ability to
      fly for up to 3 h. However, in comparison to not-flown birds, bacterial killing
      ability of plasma was significantly reduced after flight in flown-sick birds. In
      flown-healthy birds, voluntary flight duration was positively correlated with
      bacterial killing ability and baseline haptoglobin concentration of the blood
      plasma measured 1-3 weeks before experimental flights, suggesting that high
      quality birds had strong immune systems and greater flight capacity. Our findings
      indicate that flight performance is not diminished by prior immune challenge, but
      that flight while mounting an acute phase response negatively affects other
      aspects of immune function. These findings have important implications for our
      understanding of the transmission of avian diseases, as they suggest that birds
      can still migrate while fighting an infection. 

PMID- 23531821
TI  - Sleep deprivation attenuates endotoxin-induced cytokine gene expression
      independent of day length and circulating cortisol in male Siberian hamsters
      (Phodopus sungorus).
AB  - Sleep is restorative, whereas reduced sleep leads to negative health outcomes,
      such as increased susceptibility to disease. Sleep deprivation tends to attenuate
      inflammatory responses triggered by infection or exposure to endotoxin, such as
      bacterial lipopolysaccharide (LPS). Previous studies have demonstrated that
      Siberian hamsters (Phodopus sungorus), photoperiodic rodents, attenuate LPS
      induced fever, sickness behavior and upstream pro-inflammatory gene expression
      when adapted to short day lengths. Here, we tested whether manipulation of
      photoperiod alters the suppressive effects of sleep deprivation upon cytokine
      gene expression after LPS challenge. Male Siberian hamsters were adapted to long
      (16 h:8 h light:dark) or short (8 h:16 h light:dark) photoperiods for >10 weeks,
      and were deprived of sleep for 24 h using the multiple platform method or
      remained in their home cage. Hamsters received an intraperitoneal injection of
      LPS or saline (control) 18 h after starting the protocol, and were killed 6 h
      later. LPS increased liver and hypothalamic interleukin-1 (IL-1) and tumor
      necrosis factor-alpha (TNF) gene expression compared with vehicle. Among LPS
      challenged hamsters, sleep deprivation reduced IL-1 mRNA levels in liver and
      hypothalamus, but not TNF. IL-1 attenuation was independent of circulating
      baseline cortisol, which did not increase after sleep deprivation. Conversely,
      photoperiod altered baseline cortisol, but not pro-inflammatory gene expression
      in sleep-deprived hamsters. These results suggest that neither photoperiod nor
      glucocorticoids influence the suppressive effect of sleep deprivation upon LPS
      induced inflammation. 

PMID- 23531822
TI  - High-frequency electrical stimulation reveals a p38-mTOR signaling module
      correlated with force-time integral.
AB  - High-frequency electrical stimulation (HFES) leads to muscle hypertrophy, and
      attention has been drawn to the high forces involved. However, both mechanical
      and metabolic stresses occur simultaneously, and both stimuli influence signaling
      cascades related to protein synthesis. This study aimed to identify the immediate
      signaling correlates of contraction-induced force and metabolic stresses under
      the hypothesis that HFES induces growth-related signaling through mechanical
      stimulation. Force-time integral (FTI) signaling in mouse tibialis anterior
      muscle was examined by separately manipulating the time of contraction to
      emphasize the metabolic aspect or the force of contraction to emphasize the
      mechanical aspect. When FTI was manipulated by changing the total time of
      activation, phosphorylation of p54 JNK, ERK and p70S6k(T421/S424) was independent
      of FTI, while phosphorylation of acetyl-CoA carboxylase and p38 correlated with
      FTI. When FTI was manipulated by changing the force of contraction, p54 JNK, ERK
      and p70S6k(T421/S424) were again independent of FTI, while phosphorylation of p38
      and FAK correlated with FTI. Factor analysis identified a p38-mTOR signaling
      module that correlated with FTI in both experiments. The consistent link among
      p38, mTOR and FTI suggests that they form a connected signaling module sensitive
      to the mechanical aspects of FTI, separate from markers of metabolic load. 

PMID- 23531823
TI  - The physiological response of the marine platyhelminth Macrostomum lignano to
      different environmental oxygen concentrations.
AB  - The respiration rate of meiofauna is difficult to measure, and the response to
      variations in the environmental oxygen concentration has so far been mainly
      addressed through behavioral investigation. We investigated the effect of
      different oxygen concentrations on the physiology of the marine platyhelminth
      Macrostomum lignano. Respiration was measured using batches of 20 animals in a
      glass microtiter plate equipped with optical oxygen sensor spots. At higher
      oxygen saturations (>12 kPa), the animals showed a clear oxyconforming behavior.
      However, below this value, the flatworms kept respiration rates constant at
      0.064+/-0.001 nmol O2 l(-1) h(-1) individual(-1) down to 3 kPa PO2, and this rate
      was increased by 30% in animals that were reoxygenated after enduring a period of
      1.5 h in anoxia. Physiological changes related to tissue oxygenation were
      assessed using live imaging techniques with different fluorophores in animals
      maintained in normoxic (21 kPa), hyperoxic (40 kPa) or near-anoxic (~0 kPa)
      conditions and subjected to anoxia-reoxygenation. The pH-sensitive dyes Ageladine
      A and BCECF both indicated that pHi under near-anoxia increases by about 0.07
      0.10 units. Mitochondrial membrane potential, Deltapsim, was higher in anoxic and
      hyperoxic than in normoxic conditions (JC1 dye data). Staining with ROS-sensitive
      dyes - DHE for detection of superoxide anion (O2*(-)) formation and C-H DFFDA for
      other ROS species aside from O2*(-) (H2O2, HOO* and ONOO) - showed increased ROS
      formation following anoxia-reoxygenation treatment. Animals exposed to hyperoxic,
      normoxic and anoxic treatments displayed no significant differences in O2*(-)
      formation, whereas mitochondrial ROS formation as detected by C-H2DFFDA was
      higher after hyperoxic exposure and lowest under near-anoxia conditions compared
      with the normoxic control group. Macrostomum lignano seems to be a species that
      is tolerant of a wide range of oxygen concentrations (being able to maintain
      aerobic metabolism from extremely low PO2 up to hyperoxic conditions), which is
      an essential prerequisite for successfully dealing with the drastic environmental
      oxygen variations that occur within intertidal sediments. 

PMID- 23531824
TI  - Environmental salinity modulates the effects of elevated CO2 levels on juvenile
      hard-shell clams, Mercenaria mercenaria.
AB  - Ocean acidification due to increasing atmospheric CO2 concentrations results in a
      decrease in seawater pH and shifts in the carbonate chemistry that can negatively
      affect marine organisms. Marine bivalves such as the hard-shell clam, Mercenaria
      mercenaria, serve as ecosystem engineers in estuaries and coastal zones of the
      western Atlantic and, as for many marine calcifiers, are sensitive to the impacts
      of ocean acidification. In estuaries, the effects of ocean acidification can be
      exacerbated by low buffering capacity of brackish waters, acidic inputs from
      freshwaters and land, and/or the negative effects of salinity on the physiology
      of organisms. We determined the interactive effects of 21 weeks of exposure to
      different levels of CO2 (~395, 800 and 1500 MUatm corresponding to pH of 8.2, 8.1
      and 7.7, respectively) and salinity (32 versus 16) on biomineralization, shell
      properties and energy metabolism of juvenile hard-shell clams. Low salinity had
      profound effects on survival, energy metabolism and biomineralization of hard
      shell clams and modulated their responses to elevated PCO2. Negative effects of
      low salinity in juvenile clams were mostly due to the strongly elevated basal
      energy demand, indicating energy deficiency, that led to reduced growth, elevated
      mortality and impaired shell maintenance (evidenced by the extensive damage to
      the periostracum). The effects of elevated PCO2 on physiology and
      biomineralization of hard-shell clams were more complex. Elevated PCO2 (~800-1500
      MUatm) had no significant effects on standard metabolic rates (indicative of the
      basal energy demand), but affected growth and shell mechanical properties in
      juvenile clams. Moderate hypercapnia (~800 MUatm PCO2) increased shell and tissue
      growth and reduced mortality of juvenile clams in high salinity exposures;
      however, these effects were abolished under the low salinity conditions or at
      high PCO2 (~1500 MUatm). Mechanical properties of the shell (measured as
      microhardness and fracture toughness of the shells) were negatively affected by
      elevated CO2 alone or in combination with low salinity, which may have important
      implications for protection against predators or environmental stressors. Our
      data indicate that environmental salinity can strongly modulate responses to
      ocean acidification in hard-shell clams and thus should be taken into account
      when predicting the effects of ocean acidification on estuarine bivalves. 

PMID- 23531825
TI  - Role of oxygen consumption in hypoxia protection by translation factor depletion.
AB  - The reduction of protein synthesis has been associated with resistance to hypoxic
      cell death. Which components of the translation machinery control hypoxic
      sensitivity and the precise mechanism has not been systematically investigated,
      although a reduction in oxygen consumption has been widely assumed to be the
      mechanism. Using genetic reagents in Caenorhabditis elegans, we examined the
      effect on organismal survival after hypoxia of knockdown of 10 factors
      functioning at the three principal steps in translation. Reduction-of-function of
      all 10 translation factors significantly increased hypoxic survival to varying
      degrees, not fully accounted for by the level of translational suppression.
      Measurement of oxygen consumption showed that strong hypoxia resistance was
      possible without a significant decrease in oxygen consumption. Hypoxic
      sensitivity had no correlation with lifespan or reactive oxygen species
      sensitivity, two phenotypes associated with reduced translation. Resistance to
      tunicamycin, which produces misfolded protein toxicity, was the only phenotype
      that significantly correlated with hypoxic sensitivity. Translation factor
      knockdown was also hypoxia protective for mouse primary neurons. These data show
      that translation factor knockdown is hypoxia protective in both C. elegans and
      mouse neurons and that oxygen consumption does not necessarily determine
      survival; rather, mitigation of misfolded protein toxicity is more strongly
      associated with hypoxic protection.

PMID- 23531826
TI  - The response of the scleractinian coral Turbinaria reniformis to thermal stress
      depends on the nitrogen status of the coral holobiont.
AB  - The physiological response of the scleractinian coral Turbinaria reniformis to
      ammonium enrichment (3 MUmol l(-1)) was examined at 26 degrees C as well as
      during a 7 day increase in temperature to 31 degrees C (thermal stress). At 26
      degrees C, ammonium supplementation had little effect on the coral physiology. It
      induced a decrease in symbiont density, compensated by an increase in chlorophyll
      content per symbiont cell. Organic carbon release was reduced, likely because of
      a better utilization of the photosynthesized carbon (i.e. incorporation into
      proteins, kept in the coral tissue). The delta(15)N signatures of the ammonium
      enriched symbionts and host tissue were also significantly decreased, by 4 and
      20/00, respectively, compared with the non-enriched conditions, suggesting a
      significant uptake of inorganic nitrogen by the holobiont. Under thermal stress,
      coral colonies that were not nitrogen enriched experienced a drastic decrease in
      photosynthetic and photoprotective pigments (chlorophyll a, beta-carotene,
      diadinoxanthin, diatoxanthin and peridinin), followed by a decrease in the rates
      of photosynthesis and calcification. Organic carbon release was not affected by
      this thermal stress. Conversely, nitrogen-enriched corals showed an increase in
      their pigment concentrations, and maintained rates of photosynthesis and
      calcification at ca. 60% and 100% of those measured under control conditions,
      respectively. However, these corals lost more organic carbon into the
      environment. Overall, these results indicate that inorganic nitrogen availability
      can be important to determining the resilience of some scleractinian coral
      species to thermal stress, and can have a function equivalent to that of
      heterotrophic feeding concerning the maintenance of coral metabolism under stress
      conditions. 

PMID- 23531827
TI  - Immune function is related to adult carotenoid and bile pigment levels, but not
      to dietary carotenoid access during development, in female mallard ducks.
AB  - Immune function can be modulated by multiple physiological factors, including
      nutrition and reproductive state. Because these factors can vary throughout an
      individual's lifetime as a result of environmental conditions (affecting
      nutrition) or life-history stage (e.g. entering the adult reproduction stage), we
      must carefully examine the degree to which developmental versus adult conditions
      shape performance of the immune system. We investigated how variation in dietary
      access to carotenoid pigments - a class of molecules with immunostimulatory
      properties that females deposit into egg yolks - during three different
      developmental time points affected adult immunological and reproductive traits in
      female mallard ducks (Anas platyrhynchos). In males and females of other avian
      species, carotenoid access during development affects carotenoid assimilation
      ability, adult sexual ornamentation and immune function, while carotenoid access
      during adulthood can increase immune response and reproductive investment (e.g.
      egg-laying capacity, biliverdin deposition in eggshells). We failed to detect
      effects of developmental carotenoid supplementation on adult immune function
      [phytohemagglutinin-induced cutaneous immune response, antibody production in
      response to the novel antigen keyhole limpet hemocyanin (KLH), or oxidative
      burst, assessed by changes in circulating nitric oxide levels], carotenoid
      pigmented beak coloration, ovarian development, circulating carotenoid levels or
      concentration of bile pigments in the gall bladder. However, we did uncover
      positive relationships between circulating carotenoid levels during adulthood and
      KLH-specific antibody production, and a negative relationship between biliverdin
      concentration in bile and KLH-specific antibody production. These results are
      consistent with the view that adult physiological parameters better predict
      current immune function than do developmental conditions, and highlight a
      possible, previously unstudied relationship between biliverdin and immune system
      performance. 

PMID- 23531828
TI  - Effect of stress on female-specific ornamentation.
AB  - Signal honesty is theorized to be maintained by condition-dependent trait
      expression. However, the mechanisms mediating the condition dependence of
      sexually selected traits are often unknown. New work suggests that elevated
      glucocorticoid levels during physiological stress may play a role in maintaining
      signal honesty. Here, we experimentally examine the effect of both chronic and
      acute stress on the expression of the condition-dependent ornamentation of female
      striped plateau lizards, Sceloporus virgatus. Females were stressed either
      chronically via corticosterone implants or relatively acutely via autotomy, were
      sham manipulated or were left unmanipulated. Both stressors resulted in
      elevations in corticosterone within physiologically relevant levels, though the
      implants resulted in significantly higher levels than did autotomy.
      Corticosterone-implanted females were less likely to produce a clutch of eggs,
      but those individuals that did reproduce had reproductive output similar to that
      of females from other treatment groups. Compared with females in other groups,
      the corticosterone-implanted females tended to develop smaller ornaments that had
      less UV and orange-to-red wavelength reflectance relative to medium wavelength
      reflectance. The sex steroid hormones testosterone and estradiol were correlated
      to corticosterone levels, but did not appear to underlie the effect on ornament
      expression; of the steroids measured, only corticosterone levels were negatively
      related to ornament size and coloration. Thus, the condition-dependent
      ornamentation of female lizards is sensitive to chronic elevations in stress
      hormones, supporting their importance in the maintenance of signal honesty. 

PMID- 23531829
TI  - Soil salinity increases survival of freezing in the enchytraeid Enchytraeus
      albidus.
AB  - Enchytraeus albidus is a freeze-tolerant enchytraeid found in diverse habitats,
      ranging from supralittoral to terrestrial and spanning temperate to arctic
      regions. Its freeze tolerance is well known but the effect of salinity in this
      strategy is still poorly understood. We therefore studied the combined effect of
      salinity (0, 15, 35, 500/00 NaCl) and sub-zero temperatures (-5, -14, -20 degrees
      C) on the freeze tolerance of E. albidus collected from two distinct geographical
      regions (Greenland and Germany). A full factorial design was used to study
      survival, and physiological and biochemical end points. The effect of salinity on
      the reproduction of German E. albidus was also assessed. Exposure for 48 h to
      saline soils prior to cold exposure triggered an increase in osmolality and
      decrease in water content. Worms exposed to saline soils had an improved survival
      of freezing compared to worms frozen in non-saline soils, particularly at -20
      degrees C (survival more than doubled). Differential scanning calorimetry
      measurements showed that the fraction of water frozen at -5 and -14 degrees C was
      lower in worms exposed to 350/00 NaCl than in control worms. The lowering of ice
      content by exposure to saline soils was probably the main explanation for the
      better freeze survival in saline-exposed worms. Glucose increased with decreasing
      temperature, but was lower in saline than in non-saline soils. Thus, glucose
      accumulation patterns did not explain differences in freeze survival. Overall,
      the physiological responses to freezing of E. albidus from Greenland and Germany
      were similar after exposure to saline soils. Soil salinity up to 300/00 improved
      reproduction by a factor of ca. 10. 

PMID- 23531830
TI  - Aggressive behavior in the antennectomized male cricket Gryllus bimaculatus.
AB  - Male crickets (Gryllus bimaculatus) exhibit intensively defensive aggressive
      behavior towards attacking males most often culminating in fighting. After the
      fight, the loser no longer exhibits aggressiveness in a second, separate
      encounter with another male; rather, the defeated male exhibits avoidance
      behavior. Here, we investigated the role of sensory input from the antennae in
      male defensive aggressive behavior. When we removed antennae from males
      (antennectomized males), we found that they showed little aggressiveness towards
      each other whereas they continued to exhibit typical fighting behavior towards an
      intact male. In addition, in a second encounter, antennectomized losers showed
      significantly higher aggressiveness towards another male than did intact losers.
      We further found that antennectomized crickets do not utilize visual or palpal
      sensory input to elicit aggressive behavior. In contrast, intact males showed
      aspects of aggressive behavior to male cuticular substances before and after
      winning a fight, and if they lost a fight they showed avoidance behavior. It thus
      appears that antennal sensory information is crucial in the mediation of
      aggressive and avoidance behaviors. However, sensory inputs from the antennae are
      not necessary to elicit defensive aggressive behavior but are necessary to
      discriminate conspecific males and initiate attacks against them.

PMID- 23531831
TI  - Hydrogen sulfide in cell signaling, signal transduction, cellular bioenergetics
      and physiology in C. elegans.
AB  - Hydrogen sulfide (H2S), long viewed as a toxic gas and environmental hazard, is
      emerging as a biological mediator with remarkable physiological and
      pathophysiological relevance. H2S is now viewed as the third main gasotransmitter
      in the mammalian body. Its pharmacological characteristic possesses similarities
      to the other two gasotransmitters - nitric oxide (NO) and carbon monoxide (CO).
      Many of the biological effects of H2S follow a bell-shaped concentration
      response; at low concentration or at lower release rates it has beneficial and
      cytoprotective effects, while at higher concentrations or fast release rates
      toxicity becomes apparent. Cellular bioenergetics is a prime example for this
      bell-shaped dose-response, where H2S, at lower concentrations/rates serves as an
      inorganic substrate and electron donor for mitochondrial ATP generation, while at
      high concentration it inhibits mitochondrial respiration by blocking the Complex
      IV in the mitochondrial electron transport chain. The current review is aimed to
      focus on the following aspects of H2S biology: 1) a general overview of the
      general pharmacological characteristics of H2S, 2) a summary of the key H2S
      mediated signal transduction pathways, 3) an overview of role of H2S in
      regulation of cellular bioenergetics, 4) key aspects of H2S physiology in C.
      elegans (a model system) and, finally 5) the therapeutic potential of H2S
      donating molecules in various disease states.

PMID- 23531832
TI  - Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels
      in human erythrocytes.
AB  - Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used
      in biological research, cryobiology and medicine. On cellular level DMSO was
      shown to suppress NMDA-AMPA channels activation, blocks Na+ channel activation
      and attenuates Ca2+ influx (Lu and Mattson 2001). In the present study we
      explored the whole-cell patch-clamp to examine the acute effect of high
      concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human
      erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl--containing
      saline buffer solution significantly inhibited cation conductance in human
      erythrocytes. Inhibition was concentration-dependent and had an exponential decay
      profile. DMSO (2 mol/l) induced cation inhibition in Cl-- containing saline
      solutions of: 40.3 +/- 3.9% for K+, 35.4 +/- 3.1% for Ca2+ and 47.4 +/- 1.9% for
      NMDG+. Substitution of Cl- with gluconate- increased the inhibitory effect of
      DMSO on the Na+ current. Inhibitory effect of DMSO was neither due to high
      permeability of erythrocytes to DMSO nor to an increased tonicity of the bath
      media since no effect was observed in 2 mol/l glycerol solution. In conclusion,
      we have shown that high concentrations of DMSO inhibit the non-selective cation
      channels in human erythrocytes and thus protect the cells against Na+ and Ca2+
      overload. Possible mechanisms of DMSO effect on cation conductance are discussed.

PMID- 23531833
TI  - Suppression of membrane vesiculation as anticoagulant and anti-metastatic
      mechanism. Role of stability of narrow necks.
AB  - Nanovesicles that are pinched off from biological membranes in the final stage of
      budding constitute a cell-cell communication system. Recent studies indicate that
      in vivo they are involved in blood clot formation and in cancer progression. The
      bud is connected to the mother membrane by a thin neck so it dwells close to the
      mother membrane. Using the electron microscopy we have observed in blood cells
      that adhesion between the membrane of the bud and of the mother cell in the
      vicinity of the neck took place and prevented the bud to pinch off from the
      mother vesicle. The same effect was observed in giant phospholipid vesicles
      (GPVs) due to attractive interaction between the bud and the mother vesicle
      mediated by the plasma protein beta-2-glycoprotein I. The stability of the neck
      is important for this process. By using Fourier method we analyzed thermal
      fluctuations of a GPV while a protrusion composed of beads connected by thin
      necks was spontaneously integrated into the mother GPV. Stepwise change of
      Fourier coefficients indicates an increased stability of necks which contributes
      to the retention of buds by the mother membrane and promotes anticoagulant and
      anti-metastatic mechanism by suppression of nanovesiculation.

PMID- 23531834
TI  - Effects of selenoprotein P on the contraction and relaxation of the airway smooth
      muscle.
AB  - Selenoprotein P (SeP) not only represents the major selenoprotein in plasma, but
      also provides more than 50% of the total plasma selenium. However, there is no
      report concerning the direct action of selenium or selenium-containing compounds
      on the contraction and relaxation of the airway smooth muscle. Therefore, we
      investigated the effects of SeP and sodium selenite (SS) on the indirectly
      induced contraction and relaxation of the cat bronchi, and gel contraction of
      cultured bovine tracheal smooth muscle cells (BTSMC) induced by ATP. In the
      present results, SeP or SS suppressed the amplitude of twitch-like contractions
      of cat bronchiole without affecting the non-adrenergic and non-cholinergic (NANC)
      relaxations evoked by electrical field stimulation. SeP also suppressed the ATP
      induced gel contraction of BTSMC. These results suggest that SeP suppresses the
      amplitude of twitch-like contraction of cat bronchiole by acting directly on the
      bronchiolar smooth muscle.

PMID- 23531835
TI  - Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin,
      PARK2) genes mutations in Slovak Parkinson disease patients.
AB  - Parkinson disease (PD) is a chronic neurodegenerative movement disorder
      characterized by selective loss of nigrostriatal dopaminergic neurons and
      formation of Lewy bodies. Clinical manifestations include motor impairments
      involving tremor, bradykinesia, postural instability and rigidity. Using dHPLC
      method we screened exons 31, 35, 41, 48 of the Leucine-rich repeat kinase 2
      (LRRK2) gene and exons 2, 6 and 7 of Parkinson protein 2 (parkin, PARK2) genes in
      a cohort of 216 consecutive, unrelated Slovak patients with familial or sporadic
      PD, including early and late onset. By this means we aimed to detect the most
      common pathogenic mutations within LRRK2 (Arg1441Cys, Arg1441Gly, Arg1628Pro,
      Tyr1699Cys, Gly2019Ser, Ile2020Thr, Gly2385Arg) and parkin genes responsible for
      late and early onset forms of disease, respectively. However, none of these
      mutations was identified in our cohort. Heterozygous point mutation p.Arg275Trp
      in exon 7 of parkin gene was identified in one patient with age at onset 61
      years. Furthermore, we observed the presence of one exonic (LRRK2 ex 48: 7155A>G)
      and eight intronic polymorphisms (in LRRK2: IVS35+23T>A, IVS47-91insGCCAT, IVS47
      91insGCAT, IVS47-41A>G, IVS47-9delT, IVS47-20C>T, IVS47-90A>G, in parkin:
      IVS2+25T>C), three of which were novel.

PMID- 23531836
TI  - A viscometric approach of pH effect on hydrodynamic properties of human serum
      albumin in the normal form.
AB  - The paper presents the results of viscosity determinations on aqueous solutions
      of human serum albumin (HSA) at isoelectric point over a wide range of
      concentrations and at temperatures ranging from 5 degrees C to 45 degrees C. On
      the basis of a modified Arrhenius equation and Mooney's formula some hydrodynamic
      parameters were obtained. They are compared with those previously obtained for
      HSA in solutions at neutral pH. The activation energy and entropy of viscous flow
      and the intrinsic viscosity reach a maximum value, and the effective specific
      volume, the self-crowding factor and the Huggins coefficient a minimum value in
      solutions at isoelectric point. Using the dimensionless parameter [eta]c, the
      existence of three ranges of concentrations: diluted, semi-diluted and
      concentrated, was shown. By applying Lefebvre's relation for the relative
      viscosity in the semi-dilute regime, the Mark-Houvink-Kuhn-Sakurada (MHKS)
      exponent was established. The analysis of the results obtained from the three
      ranges of concentrations showed that both conformation and stiffness of HSA
      molecules in solutions at isoelectric point and at neutral pH are the same.

PMID- 23531837
TI  - Melatonin protects rat thymus against oxidative stress caused by exposure to
      microwaves and modulates proliferation/apoptosis of thymocytes.
AB  - The aim of the study was to evaluate the effect of melatonin on oxidative stress,
      DNA fragmentation, apoptsis and proliferation in thymus tissue of rats exposed to
      microwaves. Wistar rats were divided in four groups: I - treated with saline; II 
      treated with melatonin; III - microwaves exposed; IV - microwaves exposed and
      melatonin treated. Melatonin (2 mg/kg i.p.) was administered daily. Animals were
      sacrificed after 20, 40 and 60 days. A significant increase in malondialdehyde
      and carbonyl group content, as well as decrease in catalase and increase in
      xanthine oxidase activity were registered under microwave exposure. Melatonin
      prevented the increase in malondialdehyde and carbonyl group content, and
      reversed the effect on catalase and xanthine oxidase activity. Both, alkaline and
      acid DNase activity were increased due to microwave exposure. Furthermore,
      microwaves caused increase in apoptosis rate (detected using Annexin V-FITC/PI
      kit) and reduced proliferative capacity of thymocytes (induced by ConA). However,
      melatonin caused decrease in alkaline and acid DNase activity, decrease in
      apoptotic rate and increase in proliferation rate of thymocytes. Melatonin exerts
      protective effects on rat thymocytes by modulating processes of apoptosis and
      proliferation, and causes decrease in DNA fragmentation and oxidative stress
      intensity under exposure to microwaves.

PMID- 23531838
TI  - Long-term alterations of cell population in the adult rat forebrain following the
      exposure to fractionated doses of ionizing radiation.
AB  - We investigated radiation-induced delayed alterations of proliferating
      population, cells undergoing apoptosis and glial cells housed rat brain
      neurogenic region. Adult male Wistar rats were investigated 30, 60 or 90 days
      after whole-body irradiation with fractionated doses of gamma rays (the total
      dose of 4 Gy). Using immunohistochemistry for detection of cell proliferation
      marker Ki-67, caspase3 as apoptotic marker and GFAP for mature astrocytes we have
      been performed quantitative analysis in different forebrain's areas along the SVZ
      OB axis, i.e. in the anterior subvetricular zone (SVZa), vertical arm, elbow and
      horizontal arm. In animals that survived thirty days after radiation treatment
      initial decrease of the Ki-67-positive cells was seen in regions along the SVZ-OB
      axis. The highest increase was observed in vertical arm on the 60th day followed
      by the most striking decline on the 90th day after irradiation. Cells undergoing
      apoptosis didn't showed expressive increase during entire experiment except of
      horizontal arm. The most striking changes of GFAP-positive cells were seen 30 and
      60 days after irradiation in vertical arm and elbow. Results suggested that
      radiation response of proliferating cells and astrocytes resides the SVZa may
      play contributory role in development of more adverse radiation-induced late
      effects.

PMID- 23531839
TI  - GABA-induced vasorelaxation mediated by nitric oxide and GABAA receptor in non
      diabetic and streptozotocin-induced diabetic rat vessels.
AB  - Diabetes has profound, negative effects on the function of arteries and
      arterioles. Hypertension is considered an independent risk factor for
      cardiovascular mortality in diabetic patients. The present study was designed to
      determine whether GABA-induced vasorelaxation in normal and streptozotocin
      induced diabetic rat vessels is mediated by nitric oxide and the GABAA receptor.
      Diabetes was induced by a single intraperitoneal injection of streptozotocin
      (STZ) (60 mg/kg). Eight weeks later, superior mesenteric arteries of all groups
      were isolated and perfused according to the McGregor method. Baseline perfusion
      pressure of STZ diabetic rats was significantly higher than non-diabetic rats in
      both intact and denuded endothelium. In the presence of bicuculline, a selective
      GABAA receptor blocker, GABA-induced relaxation in intact and denuded endothelium
      mesenteric beds of non-diabetic and STZ diabetic rats was suppressed. But in the
      presence of L-NAME, a nitric oxide synthesis inhibitor, although GABA- induced
      vasorelaxation was not suppressed at a dose of 1 uM of GABA in all groups, this
      response was suppressed with the other doses of GABA. From the results of this
      study it may be concluded that the vasorelaxatory effect of GABA is mediated by
      the GABAA receptor and nitric oxide in both STZ diabetic and non-diabetic
      vessels.

PMID- 23531840
TI  - 5-HT1A receptor-mediated activation of outward potassium current by serotonin in
      mouse cultured spiral ganglion neurons.
AB  - Cochlear spiral ganglion neurons provide the only pathway for transmitting sound
      evoked activity from the hair cells to the central auditory system. Serotonin
      plays a role in the response properties of central auditory neurons. However,
      knowledge about the role of serotonin in the peripheral auditory nervous system
      remains limited. In the current study, we investigated the influence of serotonin
      on outward potassium current in mouse cultured spiral ganglion neurons using
      whole-cell patch clamp technique. The cell capacitance was 4.03 +/- 0.18 pF (n =
      54). Application of serotonin caused an increase of outward potassium currents
      within seconds, whereas treatment with WAY100635, a selective 5-HT1A receptor
      antagonist, counteracted the increase effect of serotonin. These results suggest
      that serotonin increases outward potassium currents in cultured spiral ganglion
      neurons through the activation of 5-HT1A receptor. Serotonin may play an
      important role in sound transmission.

PMID- 23531841
TI  - Phytochemical, antioxidant and protective effect of Rhus tripartitum root bark
      extract against ethanol-induced ulcer in rats.
AB  - Rhus tripartitum (sumac) is an Anacardiaceae tree with a wide phytotherapeutic
      application including the use of its roots in the management of gastric ulcer. In
      the present study the Rhus tripartitum root barks extract (RTE) was phytochemical
      studied, in vitro tested for their potential antioxidant activity using 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and reducing power assay and in vivo evaluated
      for its ability to prevent ethanol-induced gastric ulcer in rats. The RTE was
      rich in phenolics, flavonoids, tannins and polysaccharide contents and exhibited
      a low but not weak in vitro antioxidant activity when compared with (+)-catechin.
      Pre-treatment with RTE at oral doses 50, 200 and 400 mg/kg body weight was found
      to provide a dose-dependent protection against ethanol-induced ulcer by averting
      the deep ulcer lesions of the gastric epithelium, by reducing gastric juice and
      acid output, by enhancing gastric mucus production by preserving normal
      antioxidant enzymes activities, and inhibiting the lipid peroxidation. The
      antiulcerogenic activity of RTE might be due to a possible synergistic
      antioxidant and antisecretory effects.

PMID- 23531842
TI  - Maternal restraint stress negatively influences growth capacity of
      preimplantation mouse embryos.
AB  - In our study we investigated the effect of maternal restraint stress on
      preimplantation embryo development using a mouse model. We exposed hormonally
      stimulated (superovulated) and unstimulated (i.e. spontaneously ovulating) mouse
      females to restraint stress for 30 min three times a day during the
      preimplantation period. The stress exposure caused significant increase in blood
      plasma corticosterone concentration. Microscopical evaluation of embryos isolated
      from spontaneously ovulating females showed that maternal stress significantly
      increased the proportion of embryos with lower cell numbers (<=32 cells) and
      decreased the proportion of embryos with higher cell numbers (65-96 cells and 97
      128 cells). Moreover maternal restraint stress decreased the cell counts per
      embryo and per blastocyst. After an additional 24 h in vitro culture we did not
      find any difference in the embryo distribution or in the cell counts per
      embryo/blastocyst between embryos isolated from stressed and control mothers. The
      exposure to restraint stress did not affect the incidence of apoptosis in
      blastocysts isolated from spontaneously ovulated dams. In gonadotropin stimulated
      dams, the hormonal treatment itself notably changed embryo distribution
      (increasing the proportion of degenerated embryos) and increased the occurrence
      of apoptotic cells. Our results indicate that psychical stress exposure in very
      early pregnancy can significantly influence the developmental capacity of
      preimplantation embryos.

PMID- 23531843
TI  - Brain-derived neurotrophic factor blood levels in two models of transient brain
      ischemia in rats.
AB  - We monitored possible influence of transient focal and global brain ischemia on
      BDNF blood level. In both models noticeable fluctuation of BDNF concentration
      mainly in reperfusion was observed. During the first 90 min, BDNF in total blood
      and in blood cells continuously decreased in both models but plasma BDNF raised
      at 40 min and peaked at 90 min of reperfusion. Our data confirm the impact of
      transient brain ischemia on BDNF levels in the circulatory system, suggest blood
      cells as a possible source of BDNF and demonstrate the interdependence of blood
      compartments and physiological state of an affected organism.

PMID- 23531844
TI  - Excluded volume effect of counterions and water dipoles near a highly charged
      surface due to a rotationally averaged Boltzmann factor for water dipoles.
AB  - Water ordering near a negatively charged electrode is one of the decisive factors
      determining the interactions of an electrode with the surrounding electrolyte
      solution or tissue. In this work, the generalized Langevin-Bikerman model
      (Gongadze-Iglic model) taking into account the cavity field and the excluded
      volume principle is used to calculate the space dependency of ions and water
      number densities in the vicinity of a highly charged surface. It is shown that
      for high enough surface charged densities the usual trend of increasing
      counterion number density towards the charged surface may be completely reversed,
      i.e. the drop in the counterions number density near the charged surface is
      predicted.

PMID- 23531845
TI  - Radio-metabolite analysis of carbon-11 biochemical partitioning to non-structural
      carbohydrates for integrated metabolism and transport studies.
AB  - Metabolism and phloem transport of carbohydrates are interactive processes, yet
      each is often studied in isolation from the other. Carbon-11 ((11)C) has been
      successfully used to study transport and allocation processes dynamically over
      time. There is a need for techniques to determine metabolic partitioning of newly
      fixed carbon that are compatible with existing non-invasive (11)C-based
      methodologies for the study of phloem transport. In this report, we present
      methods using (11)C-labeled CO2 to trace carbon partitioning to the major non
      structural carbohydrates in leaves-sucrose, glucose, fructose and starch. High
      performance thin-layer chromatography (HPTLC) was adapted to provide multisample
      throughput, raising the possibility of measuring different tissues of the same
      individual plant, or for screening multiple plants. An additional advantage of
      HPTLC was that phosphor plate imaging of radioactivity had a much higher
      sensitivity and broader range of sensitivity than radio-HPLC detection, allowing
      measurement of (11)C partitioning to starch, which was previously not possible.
      Because of the high specific activity of (11)C and high sensitivity of detection,
      our method may have additional applications in the study of rapid metabolic
      responses to environmental changes that occur on a time scale of minutes. The use
      of this method in tandem with other (11)C assays for transport dynamics and whole
      plant partitioning makes a powerful combination of tools to study carbohydrate
      metabolism and whole-plant transport as integrated processes.

PMID- 23531846
TI  - Division of shape-standardized tobacco cells reveals a limit to the occurrence of
      single-criterion-based selection of the plane of symmetric division.
AB  - The plane of symmetric plant cell division tends to be selected so that the new
      cross-wall halving the cell volume has the least possible area, and several cases
      of such selection are best represented by a recently formulated model which
      promotes the view that the strength of the least area tendency is the only
      criterion for selecting the plane. To test this model, the present study examined
      the divisions of two types of shape-standardized tobacco BY-2 cell, oblate
      spheroidal (os) cells prepared from protoplasts and spheri-cylindrical (sc) cells
      with unusual double-wall structures prepared from plasmolyzed cells. Measurements
      of cell shape parameters and division angles revealed that both cell types most
      frequently divide nearly along their short axes. While os cells did not exhibit
      any other division angle bias, sc cell division was characterized by another bias
      which made the frequency of longitudinal divisions secondarily high. The geometry
      of sc cells barely allows the longitudinal cross-walls to have locally minimum
      areas. Nevertheless, a comparison of detected and hypothetical standard divisions
      indicates that the frequency of longitudinal sc cell division can be
      significantly higher than that predicted when the longitudinal cross-walls are
      assumed to have locally minimum areas smaller than their original areas. These
      results suggest that, even in isolated plant cell types, the strength of the
      least area tendency is not the only criterion for selecting the division plane.
      The possibility that there is another basic, though often hidden, criterion is
      discussed.

PMID- 23531848
TI  - Overexpression of survivin and caspase 3 in oral carcinogenesis.
AB  - Survivin is an inhibitor of apoptosis protein that inhibits caspase 3 function.
      While cytoplasmic survivin suppresses apoptosis, nuclear survivin regulates cell
      division. Little is known about the subcellular localization of survivin in oral
      carcinogenesis. This study examined the subcellular distribution of these 2
      proteins in oral squamous cell carcinoma (OSCC) and premalignant lesions
      including oral leukoplakia (OL) with and without dysplasia. Expression of
      survivin and caspase 3 were immunohistochemically analyzed in 114 samples
      including OSCC, OL with and without dysplasia, and normal oral mucosa (NM).
      Cytoplasmic and nuclear positive cells were counted separately. The results were
      presented as the frequency of positive cases. The positive expression rates of
      cytoplasmic and nuclear survivin in OSCC were significantly higher than in NM, OL
      with and without dysplasia. NM showed a low rate of cytoplasmic survivin
      expression compared to OL with and without dysplasia. The numbers of cytoplasmic
      and nuclear expression of caspase 3 in OSCC were significantly higher than that
      of NM, OL with and without dysplasia. In conclusion, the overexpression of
      cytoplasmic survivin in OSCC and premalignant lesions suggest that suppression of
      apoptosis by survivin occurs at early and late stages of oral carcinogenesis. The
      elevated expression of nuclear survivin and caspase 3 in OSCC indicate that at
      the late stage survivin increases cell proliferation whereas caspase 3 promotes
      apoptosis.

PMID- 23531847
TI  - A population-based case-control study of stillbirth: the relationship of
      significant life events to the racial disparity for African Americans.
AB  - Stillbirths (fetal deaths occurring at >=20 weeks' gestation) are approximately
      equal in number to infant deaths in the United States and are twice as likely
      among non-Hispanic black births as among non-Hispanic white births. The causes of
      racial disparity in stillbirth remain poorly understood. A population-based case
      control study conducted by the Stillbirth Collaborative Research Network in 5 US
      catchment areas from March 2006 to September 2008 identified characteristics
      associated with racial/ethnic disparity and interpersonal and environmental
      stressors, including a list of 13 significant life events (SLEs). The adjusted
      odds ratio for stillbirth among women reporting all 4 SLE factors (financial,
      emotional, traumatic, and partner-related) was 2.22 (95% confidence interval:
      1.43, 3.46). This association was robust after additional control for the
      correlated variables of family income, marital status, and health insurance type.
      There was no interaction between race/ethnicity and other variables. Effective
      ameliorative interventions could have a substantial public health impact, since
      there is at least a 50% increased risk of stillbirth for the approximately 21% of
      all women and 32% of non-Hispanic black women who experience 3 or more SLE
      factors during the year prior to delivery.

PMID- 23531849
TI  - Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review
      and update.
AB  - Podoplanin is a type I integral membrane glycoprotein that, because it is
      expressed in lymphatic endothelium, but not in vascular blood vessel endothelial
      cells, is commonly used in the identification of lymphatic endothelial
      differentiation in vascular endothelial neoplasms and lymphatic invasion by
      tumor. Because podoplanin is also expressed in mesothelial cells and fetal
      gonocytes, it has proved to be a useful marker for assisting in the differential
      diagnosis of mesotheliomas and germ cell tumors, particularly
      seminomas/dysgerminomas. Podoplanin expression has also been reported in a wide
      variety of other neoplasms, including hemangioblastomas, meningiomas,
      cartilaginous tumors, and follicular dendritic cell neoplasms. This article
      reviews the information that is currently available on the application of
      podoplanin immunostaining in diagnostic pathology. 

PMID- 23531850
TI  - Adrenocortical carcinoma: a comprehensive immunohistochemical study of 40 cases.
AB  - Adrenocortical carcinomas (ACC) are uncommon tumors of the adrenal cortex that
      are known to follow an aggressive clinical course. The distinction of these
      tumors from other neoplasms may sometimes prove difficult due to overlapping
      clinical, morphologic, and even immunophenotypical features. To this end, we
      performed a comprehensive immunohistochemical analysis using traditional and
      novel markers in 40 cases of ACC. An immunohistochemical panel consisting of 10
      traditional and novel antibodies was applied to whole tissue sections of ACC
      including high-molecular weight cytokeratin (HMWCK), low-molecular weight
      cytokeratin (CAM5.2), inhibin-alpha, melan A, chromogranin A, synaptophysin,
      calretinin, steroid receptor coactivator-1 (SRC-1), Pax8, and Ki67. The
      percentage of positive tumor cells as well as the intensity of staining were
      evaluated and scored; for Ki67 the percentage of positive tumor cells was
      recorded. Positive staining was observed for SRC-1 (39/40; 97.5%), inhibin-alpha
      (37/40; 92.5%), calretinin (32/40; 80%), synaptophysin (29/40; 72.5%), melan A
      (26/40; 65%), and CAM5.2 (9/40; 22.5%). Rare cases showed positivity for
      chromogranin A (2/40; 5%) and Pax8 (1/40; 2.5%). None of the cases showed any
      reactivity with HMWCK. The Ki67 index ranged from <5% to 20%. We conclude that
      there is no single specific marker to reliably distinguish ACC from other primary
      or metastatic neoplasms. However, a combination of immunohistochemical stains in
      a panel consisting of SRC-1, inhibin-alpha, calretinin, and HMWCK may be of aid
      in the differential diagnosis of these tumors. In addition, Pax8 is only rarely
      positive in ACC, which is a useful tool in their separation from renal neoplasms.

PMID- 23531851
TI  - Significant expression of thyroid transcription factor-1 in pulmonary squamous
      cell carcinoma detected by SPT24 monoclonal antibody and CSA-II system.
AB  - In contrast to the usefulness of thyroid transcription factor-1 (TTF-1) in
      distinguishing primary adenocarcinoma of the lung from metastatic lesions, TTF-1
      expression in pulmonary squamous cell carcinoma is reported to be at low level
      and not a suitable immunohistochemical marker. We hypothesized that the highly
      sensitive detection system, CSA-II, can visualize even faint expression of TTF-1
      in pulmonary squamous cell carcinoma. In this study, 2 commercially available
      clones of TTF-1 monoclonal antibody, 8G7G3/1 and SPT24, were used for staining 38
      cases of pulmonary squamous cell carcinoma, in combination with the CSA-II and
      the conventional detection system, EnVision. The combined use of the 8G7G3/1
      clone with EnVision and CSA-II showed a positive reaction in only 1 and 4 cases,
      respectively. The use of SPT24 clone showed positive staining in 5 cases with
      EnVision and in 20 of 38 cases (52.6%) with the CSA-II. Interestingly, positive
      staining by the SPT24-CSA-II technique of samples from tissue blocks preserved
      for <2 years was 73.6% compared with only 31.5% in those preserved for >2 years.
      In addition, a 6-month preservation of the cut sections resulted in stain fading
      and decreased positivity (50%), compared with freshly cut sections. We conclude
      that the use of the SPT24 monoclonal antibody with the CSA-II system can detect
      even weak expression of TTF-1 in pulmonary squamous cell carcinoma. This staining
      technique can potentially allow the discrimination of primary squamous cell
      carcinoma of the lung from metastatic lesions, especially in freshly prepared
      paraffin sections. 

PMID- 23531852
TI  - The association of urocortin expression with clinicopathologic parameters of
      gastric adenocarcinomas.
AB  - Gastric adenocarcinoma is a lethal disease with high incidence in Chinese people.
      The purpose of this study was to evaluate the expression of urocortin (UCN) in
      normal gastric mucosa and gastric adenocarcinomas. Immunohistochemical analysis
      of UCN was performed in 112 surgical specimens (21 normal gastric mucosa
      specimens and 91 gastric adenocarcinoma specimens varying in histologic grade and
      pathologic stage). Immunostain intensity was scored on a scale ranging from 0
      (absence of staining) to 3 (strong staining). The percentage of UCN stained cells
      was scored on a scale ranging from 0 (<5%) to 4 (75% to 100%). The UCN
      immunoscore (ranging from 0 to 12) was the product of the above 2 scores. The UCN
      immunoscore was high in all 9 normal gastric mucosa specimens, significantly
      lower in poorly differentiated gastric adenocarcinoma than in well and moderately
      differentiated tumors (P=0.018), and significantly lower in more advanced
      pathologic stages of gastric adenocarcinomas than in the early stages of these
      tumors. Moreover, UCN expression was higher in gastric adenocarcinomas with
      neuroendocrine differentiation than in mucinous adenocarcinomas and signet-ring
      cell carcinomas. In conclusion, UCN is expressed in most non-neoplastic gastric
      glandular epithelia. However, UCN expression inversely correlates with higher
      tumor grade and advanced TNM stage in gastric adenocarcinomas. 

PMID- 23531853
TI  - Spindle cell foci of the thyroid-mimicking malignancy: a diagnostic pitfall.

PMID- 23531854
TI  - Androgen receptor expression in vascular neoplasms of the breast.
AB  - INTRODUCTION: Androgen receptors (AR) have been reported to be present in normal
      breast tissue and breast carcinomas. The following study was undertaken to assess
      the expression of AR in vascular neoplasms of the breast. MATERIALS AND METHODS:
      All patients with histologically diagnosed hemangioma, angiolipoma, atypical
      vascular proliferation, and angiosarcoma of the breast were retrieved from the
      clinical and pathology database at Rush University Medical Center. The slides
      stained with hematoxylin and eosin were reviewed and immunohistochemical staining
      for AR (Dako; clone AR441) was performed on paraffin-embedded tissue. Any amount
      of nuclear staining was considered positive and the intensity of staining was
      graded as 1+ to 3+. An estimate of the percentage of tumor and stromal cells
      staining was made. RESULTS: There were a total of 36 cases, 10 hemangiomas, 20
      angiolipomas, 2 atypical vascular proliferation, and 4 angiosarcomas. The male to
      female ratio was 1:4.1. The average age at presentation for men was 45 years and
      for women was 56.9 years. Anti-AR expression was present in stromal and adipocyte
      nuclei of the angiolipomas and stromal cells of hemangiomas and angiosarcomas.
      Interestingly, normal duct epithelium of the breast was positive in 7 of the 29
      women and none in men. Androgen expression was present in 62.5% of the
      hemangiomas, 55% of the angiolipomas, and 50% of the angiosarcomas. The majority
      of tumors showed a low-intensity nuclear expression of androgens, with 1+
      intensity in 13 cases and 2+ intensity seen in 2 cases, and only 1 case of
      angiolipoma showed 3+ expression. All positive cases of angiolipoma (55%) showed
      AR in adipocytes and stromal cells. CONCLUSIONS: Vascular neoplasms are uncommon
      tumors in breast and majority of them are benign. Androgen expression is present
      in >50% of benign vascular neoplasms. Stromal cells and adipocytes typically
      express AR only in angiolipomas, suggesting a role of androgens in pathogenesis
      and growth of this neoplasm.

PMID- 23531855
TI  - Sorting Nexin 2 (SNX2): a potential marker of active thyrocytes in normal and
      hyperfunctioning thyroid disorders.
AB  - Sorting nexins (SNXs) are a large, diverse group of cytoplasmic and membrane
      associated proteins that function in a variety of cellular processes, including
      endocytosis, protein trafficking, and the retrieval of transmembrane proteins. In
      this study, we demonstrated that SNX2 is expressed in columnar and active thyroid
      follicular cells but not in flattened inactive thyrocytes. Morphometric analysis
      revealed a significant correlation between SNX2 positivity and columnar cell
      morphology. Immunohistochemical staining of serial sections of the thyroid tissue
      indicated that SNX2 localization was similar to sortilin, a protein expressed by
      active thyrocytes. Expression of SNX2 in thyrocytes is particularly marked and
      extensive in most hyperstimulated thyroid disorders, including Graves disease
      (diffusely SNX2 positive in 73.3% patients) and functioning nodules (93.8%
      patients). SNX2 immunolocalization in hyperstimulated follicular epithelial cells
      was specific among the SNXs family members examined. These results support the
      utility of SNX2 as a novel marker of active thyrocytes and reflect the endosomal
      trafficking activity in these cells. 

PMID- 23531856
TI  - Mapping of succinate dehydrogenase losses in 2258 epithelial neoplasms.
AB  - Losses in the succinate dehydrogenase (SDH) complex characterize 20% to 30% of
      extra-adrenal paragangliomas and 7% to 8% of gastric GISTs, and rare renal cell
      carcinomas. This loss is reflected as lack of the normally ubiquitous
      immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas,
      SDHB loss correlates with homozygous loss of any of the SDH subunits, typically
      by loss-of-function mutations. The occurrence of SDHB losses in other epithelial
      malignancies is unknown. In this study, we immunohistochemically examined 2258
      epithelial, mostly malignant neoplasms including common carcinomas of all sites.
      Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%),
      including a patient with an SDHB-deficient GIST. Histologically, the SDHB
      negative renal carcinomas varied. There was 1 clear cell carcinoma with a high
      nuclear grade, 1 papillary carcinoma type 2, 1 unclassified carcinoma with a
      glandular pattern, and 1 oncocytoid low-grade carcinoma as previously described
      for SDHB-negative renal carcinoma. None of these patients was known to have
      paragangliomas or had loss of SDHA expression in the tumor. Three of these
      patients had metastases at presentation (2 in the adrenal, 1 in the
      retroperitoneal lymph nodes). There were no cases with SDHB loss among 64 renal
      oncocytomas. SDHB losses were not seen in other carcinomas, except in 1 prostatic
      adenocarcinoma (1/57), 1 lymphoepithelial carcinoma of the stomach, and 1 (1/40)
      seminoma. On the basis of this study, SDHB losses occur in 0.6% of renal cell
      carcinomas and extremely rarely in other carcinomas. Some of these renal
      carcinomas may be clinically aggressive. The clinical significance and molecular
      genetics of these SDHB-negative tumors requires further study.

PMID- 23531857
TI  - Patients with refractory epilepsy treated using a modified multiple subpial
      transection technique.
AB  - BACKGROUND: : Multiple subpial transection (MST) is a potential surgical
      treatment for patients with epileptogenic foci located in cortical areas with
      higher functions. As neurosurgical teams have become more experienced with MST,
      the original technique has adapted. OBJECTIVE: : To report our 6-year experience
      with a modified MST technique. METHODS: : The population included 62 consecutive
      patients with medically refractory epilepsy treated by MST, with a follow-up
      period ranging from 2 to 9 years. MST was performed on gyri under neuronavigation
      and guided by intraoperative electrocorticography. We performed radiating MST
      from a single cortical entry point. The MST technique was described according to
      the number of transections performed and the Brodmann areas (BAs) involved. Any
      MST-related complications were registered and followed up. Clinical outcome was
      described in terms of seizure suppression or reduction according to the Engel
      modified classification. RESULTS: : Twelve patients underwent MST alone (MSTa),
      and 50 had MST with another procedure. The main MST sites were BA 4 (61%) and 3,
      1, 2 (58%); in 22% of cases, MST was performed in BA 44, 22, 39, and 40.
      Permanent neurological deficits were observed in 4 (6.4%) patients; 2 minor
      deficits were MST related (3.2%). A reduction in the seizure rate of at least 50%
      was seen in 79% of patients (MSTa group, 75%), and 42% became seizure free (MSTa
      group, 33%). CONCLUSION: : This study demonstrates the efficacy and low morbidity
      of radiating MST performed under neuronavigation and intraoperative
      electrocorticography. ABBREVIATIONS: : BA, Brodmann areaEEG,
      electroencephalogramFDG, 18-fluorodeoxyglucoseioECoG, intraoperative
      electrocorticographyMRE, medically refractory epilepsyMST, multiple subpial
      transectionMSTa, multiple subpial transection aloneMST+, multiple subpial
      transection with other procedures.

PMID- 23531858
TI  - Self-assembled block copolymer photonic crystal for selective fructose detection.
AB  - The use of one-dimensional photonic crystals fabricated from a self-assembled
      lamellar block copolymer as a sensitive and selective fructose sensor is
      investigated. The polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP) films are
      functionalized with 2-(bromomethyl)phenylboronic acid. The boronic acid moiety
      confined within the lamellar morphology can reversibly bind to sugars such as
      fructose, imparting the photonic properties of the PS-b-P2VP film. The films
      exhibit a detection limit of 500 MUM in water and 1mM in phosphate buffered
      saline. Exposure to a 50 mM solution of fructose invokes a highly visible color
      change from blue to orange. The films are also able to selectively recognize and
      respond to fructose in competitive studies in the presence of glucose, mannose
      and sucrose.

PMID- 23531859
TI  - Electrocatalytic oxidation and determination of insulin at nickel oxide
      nanoparticles-multiwalled carbon nanotube modified screen printed electrode.
AB  - Nickel oxide nanoparticles modified nafion-multiwalled carbon nanotubes screen
      printed electrode (NiONPs/Nafion-MWCNTs/SPE) were prepared using pulsed
      electrodeposition of NiONPs on the MWCNTs/SPE surface. The size, distribution and
      structure of the NiONPs/Nafion-MWCNTs were characterized by transmission electron
      microscopy (TEM) and x-ray diffraction (XRD) and also the results show that NiO
      nanoparticles were homogeneously electrodeposited on the surfaces of MWCNTs.
      Also, the electrochemical behavior of NiONPs/Nafion-MWCNTs composites in aqueous
      alkaline solutions of insulin was studied by cyclic voltammetry,
      chronoamperometry and electrochemical impedance spectroscopy (EIS). It was found
      that the prepared nanoparticles have excellent electrocatalytic activity towards
      insulin oxidation due to special properties of NiO nanoparticles. Cyclic
      voltammetric studies showed that the NiONPs/Nafion-MWCNTs film modified SPE,
      lowers the overpotentials and improves electrochemical behavior of insulin
      oxidation, as compared to the bare SPE. Amperometry was also used to evaluate the
      analytical performance of modified electrode in the quantitation of insulin.
      Excellent analytical features, including high sensitivity (1.83 MUA/MUM), low
      detection limit (6.1 nM) and satisfactory dynamic range (20.0-260.0 nM), were
      achieved under optimized conditions. Moreover, these sensors show good
      repeatability and a high stability after a while or successive potential cycling.

PMID- 23531860
TI  - Nanodiamond based sponges with entrapped enzyme: a novel electrochemical probe
      for hydrogen peroxide.
AB  - A "modular approach" has been demonstrated for the preparation of nanodiamond
      (ND) based sponges (NS) with entrapped enzyme (horseradish peroxidase, HRP) (ND
      NS(HRP)) and utilization as an electrochemical probe for detection of hydrogen
      peroxide (H2O2). ND-NS comprises ND, porous poly(aniline)-poly(2-acrylamido 2
      methyl propane sulfonic acid) (PANI-PAMPSA) network and entrapped HRP. Field
      emission scanning electron microscope image of ND-NS(HRP) reveals sponge like
      suprastructure comprising interconnected nanospheres with numerous
      openings/pinholes/cavities. The entrapped HRP in ND-NS exhibits effective direct
      electron transfer with an electron transfer rate constant of 1.85 s(-1). ND
      NS(HRP) exhibited excellent bioelectrocatalytic reduction of hydrogen peroxide
      (H2O2) with a wide linear concentration range (1-45 mM), quick response (5s),
      high sensitivity (129.6 MUAM(-1)) and low detection limit 59 MUM (S/N=3).

PMID- 23531861
TI  - Induced opening of influenza virus neuraminidase N2 150-loop suggests an
      important role in inhibitor binding.
AB  - The recently discovered 150-cavity (formed by loop residues 147-152, N2
      numbering) adjacent to the enzymatic active site of group 1 influenza A
      neuraminidase (NA) has introduced a novel target for the design of next
      generation NA inhibitors. However, only group 1 NAs, with the exception of the
      2009 pandemic H1N1 NA, possess a 150-cavity, and no 150-cavity has been observed
      in group 2 NAs. The role of the 150-cavity played in enzymatic activity and
      inhibitor binding is not well understood. Here, we demonstrate for the first time
      that oseltamivir carboxylate can induce opening of the rigid closed N2 150-loop
      and provide a novel mechanism for 150-loop movement using molecular dynamics
      simulations. Our results provide the structural and biophysical basis of the open
      form of 150-loop and illustrates that the inherent flexibility and the ligand
      induced flexibility of the 150-loop should be taken into consideration for future
      drug design.

PMID- 23531862
TI  - PGD for hereditary breast and ovarian cancer: the route to universal tests for
      BRCA1 and BRCA2 mutation carriers.
AB  - Preimplantation Genetic Diagnosis (PGD) is a method of testing in vitro embryos
      as an alternative to prenatal diagnosis with possible termination of pregnancy in
      case of an affected child. Recently, PGD for hereditary breast and ovarian cancer
      caused by BRCA1 and BRCA2 mutations has found its way in specialized labs. We
      describe the route to universal single-cell PGD tests for carriers of BRCA1/2
      mutations. Originally, mutation-specific protocols with one or two markers were
      set up and changed when new couples were not informative. This route of changing
      protocols was finalized after 2 years with universal tests for both BRCA1 and
      BRCA2 mutation carriers based on haplotyping of, respectively, 6 (BRCA1) and 8
      (BRCA2) microsatellite markers in a multiplex PCR. Using all protocols, 30
      couples had a total of 47 PGD cycles performed. Eight cycles were cancelled upon
      IVF treatment due to hypostimulation. Of the remaining 39 cycles, a total of 261
      embryos were biopsied and a genetic diagnosis was obtained in 244 (93%). In 34 of
      the 39 cycles (84.6%), an embryo transfer was possible and resulted in 8
      pregnancies leading to a fetal heart beat per oocyte retrieval of 20.5% and a
      fetal heart beat per embryonic transfer of 23.5%. The preparation time and costs
      for set-up and validation of tests are minimized. The informativity of
      microsatellite markers used in the universal PGD-PCR tests is based on CEPH and
      deCODE pedigrees, making the tests applicable in 90% of couples coming from these
      populations. 

PMID- 23531863
TI  - An association between the PTGS2 rs5275 polymorphism and colorectal cancer risk
      in families with inherited non-syndromic predisposition.
AB  - Recently our group completed a genome-wide linkage study investigating Australian
      and Spanish families with inherited risk of colorectal cancer (CRC). A minor
      linkage peak from that study located on chromosome 1 correlates with the location
      of a known CRC risk-modifying gene, prostaglandin synthase (PTGS2). PTGS2 encodes
      the inducible prostaglandin synthase enzyme cyclooxygenase-2 (COX-2).
      Prostaglandins are implicated in the initiation of carcinogenesis and progression
      of tumours. Sequencing of PTGS2 in a small subset of affected individuals
      identified a high frequency of the minor C allele of single nucleotide
      polymorphism rs5275. We then genotyped the rs5275 polymorphism in 183 affected
      and 223 unaffected individuals from our CRC predisposed families. Tests for
      association in the presence of linkage were made using family-based association
      tests. The C allele was found to be significantly associated (P<0.01) with
      diagnosis of hereditary non-syndromic CRC (P=0.0094, dominant model) and an
      earlier age of diagnosis (P=0.0089, heterozygous-advantage model). Interestingly,
      by stratifying the age of diagnosis data, we observed a speculative gender
      discordant effect. Relative to other groups, female CC carriers were diagnosed
      less when young, but by 60 years of age were the most at risk group. Conversely,
      CT carriers of both genders showed a consistently earlier diagnosis relative to
      TT carriers. Our results suggest potential differential age-and gender-dependent
      efficacies of chemopreventative COX-2 inhibitors in the context of non-syndromic
      colorectal cancer. 

PMID- 23531864
TI  - Joint detection of association, imprinting and maternal effects using all
      children and their parents.
AB  - Genomic imprinting and maternal effects have been increasingly explored for their
      contributions to complex diseases. Statistical methods have been proposed to
      detect both imprinting and maternal effects simultaneously based on nuclear
      families. However, these methods only make use of case-parents triads and
      possibly control-parents triads, thus wasting valuable information contained in
      the siblings. More seriously, most existing methods are full-likelihood based and
      have to make strong assumptions concerning mating-type probabilities (nuisance
      parameters) to avoid over-parametrization. In this paper, we develop a partial
      Likelihood approach for detecting Imprinting and Maternal Effects (LIME), using
      nuclear families with an arbitrary number of affected and unaffected children. By
      matching affected children with unaffected ones (within or across families)
      having the same triad/pair familial genotype combination, we derive a partial
      likelihood that is free of nuisance parameters. This alleviates the need to make
      strong, yet unrealistic assumptions about the population, leading to a procedure
      that is robust to departure from Hardy-Weinberg equilibrium. Power gain by
      including siblings and robustness of LIME under a variety of settings are
      demonstrated. Our simulation study also indicates that it is more profitable to
      recruit additional siblings than additional families when the total number of
      individuals is kept the same. We applied LIME to the Framingham Heart Study data
      to demonstrate its utility in analyzing real data. Many of our findings are
      consistent with results in the literature; potentially novel genes for
      hypertension have also emerged. 

PMID- 23531865
TI  - Population structure, migration, and diversifying selection in the Netherlands.
AB  - Genetic variation in a population can be summarized through principal component
      analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable
      for genetic association studies, where they can correct for population
      stratification. We investigated how to capture the genetic population structure
      in a well-characterized sample from the Netherlands and in a worldwide data set
      and examined whether (1) removing long-range linkage disequilibrium (LD) regions
      and LD-based SNP pruning significantly improves correlations between PCs and
      geography and (2) whether genetic differentiation may have been influenced by
      migration and/or selection. In the Netherlands, three PCs showed significant
      correlations with geography, distinguishing between: (1) North and South; (2)
      East and West; and (3) the middle-band and the rest of the country. The third PC
      only emerged with minimized LD, which also significantly increased correlations
      with geography for the other two PCs. In addition to geography, the Dutch North
      South PC showed correlations with genome-wide homozygosity (r=0.245), which may
      reflect a serial-founder effect due to northwards migration, and also with height
      (?: r=0.142, ?: r=0.153). The divergence between subpopulations identified by PCs
      is partly driven by selection pressures. The first three PCs showed significant
      signals for diversifying selection (545 SNPs - the majority within 184 genes).
      The strongest signal was observed between North and South for the functional SNP
      in HERC2 that determines human blue/brown eye color. Thus, this study
      demonstrates how to increase ancestry signals in a relatively homogeneous
      population and how those signals can reveal evolutionary history. 

PMID- 23531866
TI  - Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear
      cataract in humans.
AB  - Congenital cataracts are an important cause of bilateral visual impairment in
      infants. Through genome-wide linkage analysis in a four-generation family of
      Irish descent, the disease-associated gene causing autosomal-dominant congenital
      nuclear cataract was mapped to chromosome 4p16.1. The maximum logarithm of odds
      (LOD) score was 2.62 at a recombination fraction theta=0, obtained for marker
      D4S432 physically close to the Wolfram gene (WFS1). By sequencing the coding
      regions and intron-exon boundaries of WFS1, we identified a DNA substitution
      (c.1385A-to-G) in exon 8, causing a missense mutation at codon 462 (E462G) of the
      Wolframin protein. This is the first report of a mutation in this gene causing an
      isolated nuclear congenital cataract. These findings suggest that the membrane
      trafficking protein Wolframin may be important for supporting the developing
      lens. 

PMID- 23531867
TI  - Fibroblast growth factor-2 and bone morphogenetic protein-2 have a synergistic
      stimulatory effect on bone formation in cell cultures from elderly mouse and
      human bone.
AB  - Combined regimens of fibroblast growth factor-2 (FGF-2) and bone morphogenetic
      protein-2 (BMP-2) were investigated to stimulate osteogenic differentiation. In
      young mouse calvaria-derived cells, FGF-2 (0.16ng/mL) in combination with BMP-2
      (50ng/mL) did not enhance mineralization, but in old mouse cells it resulted in
      more mineralization than BMP-2 alone. In young long bone mouse cultures, FGF-2
      enhanced mineralization relative to BMP-2 alone, but in old cultures, lower dose
      of FGF-2 (0.016ng/mL) was necessary. In neonatal mouse calvarial cells,
      sequential delivery of low-dose FGF-2 and low-dose BMP-2 (5ng/mL) was more
      stimulatory than co-delivery. In young human cultures, 0.016ng/mL of FGF-2 did
      not enhance mineralization, in combination with 5ng/mL of BMP-2, but in older
      cultures, codelivery of FGF-2 and BMP-2 was superior to BMP-2 alone. In
      conclusion, BMP-2 treatment alone was sufficient for maximal mineralization in
      young osteoblast cultures. However, coadministration of FGF-2 and BMP-2 increases
      mineralization more than BMP-2 alone in cultures from old and young mouse long
      bones and old humans but not in young mouse calvarial cultures. 

PMID- 23531868
TI  - A new index (CHOLINDEX) in detecting coronary artery disease risk.
AB  - OBJECTIVE: Coronary artery disease (CAD) risk increases with the elevation of low
      density lipoprotein cholesterol (LDL-C), triglyceride (TG) and low level high
      density lipoprotein cholesterol (HDL-C) levels. However, the magnitude at which
      CAD risk increases with every lipid parameter is controversial. We developed a
      new index called CHOLINDEX, in order to evaluate CAD risk, and investigated its
      reliability. METHODS: Three hundred and seven patients (190 males and 117
      females, aged between 26-80 years, mean 53.6 +/- 10.2 years) who underwent
      diagnostic coronary angiography were included in the study. Risk factors and
      lipid profiles of all patients were noted. CHOLINDEX was calculated by using a
      formula as follows: CHOLINDEX=LDL-C-HDL-C (TG<400 mg/dL), LDL-C-HDL-C + 1/5 of TG
      (TG >= 400 mg/dL). RESULTS: Of the 307 patients, 180 had CAD. We found that age,
      male gender, hypertension, diabetes mellitus, smoking and CHOLINDEX were
      independent predictors of CAD. The logistic regression analysis showed that the
      CHOLINDEX had a much more significant relation with CAD (odds ratio=1.011, 95%
      CI=1.003-1.019) compared with other lipid parameters. CONCLUSION: CHOLINDEX is a
      simple index which can be used reliably in prediction of CAD like other lipid
      parameters in daily clinical practice.

PMID- 23531869
TI  - Epicardial adipose tissue is independently associated with increased left
      ventricular mass in untreated hypertensive patients: an observational study.
AB  - OBJECTIVE: Epicardial adipose tissue (EAT) secretes various inflammatory
      mediators and growth factor, and has endocrine and paracrine effects on
      myocardium and body. We planned the present study in order to evaluate the
      possible relationship between EAT and left ventricular mass (LVM), a potent
      predictor of cardiovascular mortality and morbidity, independent of age, blood
      pressure and the metabolic parameters in patients with hypertension (HT).
      METHODS: The present study was cross-sectional and observational, including
      consecutive 107 untreated essential hypertensive patients who underwent a
      complete transthoracic echocardiographic examination as well as measurements of
      LVM and EAT. Blood pressure, routine blood chemistry, C-reactive protein, and
      patient characteristics were also recorded. Univariate and then multiple linear
      regression analyses were used for analysis of independent variables associated
      with EAT. RESULTS: LVM significantly correlated with waist circumference, EAT,
      glucose, uric acid, high-density lipoprotein (HDL) cholesterol, and systolic and
      diastolic blood pressure. When we divided study population into two groups
      according to median mean blood pressure (BP) (Mean BP <=116 vs. >116 mmHg), EAT
      was the only associated factor for LVM in patients below median BP (Beta: 0.518,
      p<0.001). Linear regression analyses revealed EAT to be independently associated
      with LVM (Beta: 0.419; p<0.001) and LVM index (Beta: 0.384, p<0.001) as well as
      high-density lipoprotein (Beta: -0.264, p=0.006). CONCLUSION: EAT was related to
      increased LVM independent of BMI, waist circumference, weight, systolic and
      diastolic blood pressure and other risk parameters, in patients with HT.
      Determination of increased EAT by echocardiography may have an additional value
      as an indicator of cardiovascular risk and total visceral adipose tissue.

PMID- 23531870
TI  - Subclinical left ventricular systolic dysfunction in patients with mild-to
      moderate rheumatic mitral stenosis and normal left ventricular ejection fraction:
      an observational study.
AB  - OBJECTIVE: Mitral valve stenosis (MS) remains as an important cause of morbidity
      despite evolution in diagnosis and treatment. Generally, left ventricular (LV)
      systolic functions are well preserved in patients with MS. However, there are
      some studies showing impaired LV systolic functions in patients with pure MS. The
      purpose of this study was to evaluate subclinical LV systolic dysfunction in a
      cohort of isolated mild-to-moderate MS patients with normal LV ejection fraction
      (EF) by using tissue Doppler imaging (TDI) and velocity vector imaging (VVI)
      techniques. METHODS: Fifty patients with isolated mild-to-moderate MS (84%
      female, mean age 49.1+/-10.0 years) and 60 healthy subjects (76.7% female, mean
      age 49.1+/-10.5) were included in this cross-sectional observational study.
      Conventional echocardiography, TDI, strain (S) and strain rate (SRs) analysis
      were performed in all patients. RESULTS: Transmitral mean pressure gradient was
      6.4+/-3.0 mmHg and mean mitral valve area was 1.45+/-0.36 cm2 in patients with
      MS. Both longitudinal and circumferential S and SRs were significantly reduced in
      patients with MS (p<0.001). TDI-derived parameters myocardial acceleration during
      isovolumic contraction (IVA) and peak velocity during systolic ejection (Sa) were
      also significantly decreased in patients with isolated MS (p<0.001). LV ejection
      fraction (EF) was not correlated with deformation indices. Deformation parameters
      were not correlated with transmitral gradient or mitral valve area. CONCLUSION:
      VVI-derived deformation parameters may identify subclinical systolic dysfunction
      in patients with isolated MS with normal EF. These findings may give way to
      optimal timing for mitral valve surgery.

PMID- 23531871
TI  - Role of electrocardiographic changes in discriminating acute or chronic right
      ventricular pressure overload.
AB  - OBJECTIVE: Pulmonary embolism (PE) and severe pulmonary stenosis (PS) are two
      distinct conditions accompanied by increased pressure load of the right ventricle
      (RV). Despite major advances in our understanding of the mechanisms of RV
      adaptation to the increased pressure, substantial gaps in our knowledge remain
      unsettled. One of much less known aspect of pressure overload of RV is its impact
      on electrocardiographic (ECG) changes. In this study, we aimed to study whether
      acute and chronic RV overload are accompanied by different ECG patterns. METHODS:
      Thirty-eight patients with PE underwent ECG monitoring were compared with 20
      matched patients with PS in this observational retrospective study. ECG
      abnormalities suggestive of RV overload were recorded and analyzed in both
      groups. Logistic regression analysis was used to define the predictors of chronic
      RV overload. RESULTS: Among the ECG changes studied, premature atrial contraction
      (OR-12.2, 95% CI, 1.3-107, p=0.008), right axis deviation (OR-20.4, 95% CI 4.2
      98, p<0.001), indeterminate axis (OR-0.11, 95% CI 0.02-0.44, p=0.001 0.11),
      incomplete right bundle branch block (OR-4.2, 95% CI, 1.1-15.4, p=0.02), late R
      in aVR (OR-8.4, 95% CI 2.1-33.2, p=0.001), qR in V1 lead (OR-8.3, 95% CI 1.2
      74.8, p=0.03) were found to be the independent predictors of chronic RV pressure
      overload. CONCLUSION: Our data indicate that the ECG changes that attributed to
      the acute RV pressure loading states may be more prevalent in chronic RV overload
      as compared with acute RV overload.

PMID- 23531872
TI  - The role of tenascin-C and oxidative stress in rheumatic and congenital heart
      valve diseases: an observational study.
AB  - OBJECTIVE: The aim of this study was to evaluate the association of tenascin-C
      (TnC) and total oxidant-antioxidant status to rheumatic or congenital heart valve
      diseases (HVD) in pediatric patients. METHODS: Fifty pediatric patients (25
      rheumatic HVD patients and 25 congenital HVD patients) and 20 healthy age-matched
      control subjects, aged 3-17 years, were enrolled in this observational and cross
      sectional study. Serum total antioxidant capacity (TAC), total oxidant status
      (TOS), oxidative stress index (OSI) and TnC levels were compared among the
      groups. ANOVA and Kruskal-Wallis tests were used for statistical analysis.
      RESULTS: Serum TnC level of the patients with rheumatic HVD [median 9.09 (0.94
      46.30) ng/mL] was significantly higher than both congenital HVD and control
      groups [median 2.97 (0.66-11.80) ng/mL; p<0.01, 4.72+/-1.77 ng/mL; p<0.05,
      respectively]. However, there was no statistically significant difference between
      the congenital and control groups in terms of serum TnC level. The levels of
      serum TAC, TOS and OSI were found to be statistically similar in all groups. In
      addition, there were no correlations between the level of TnC, and TOS and OSI.
      CONCLUSION: Tenascin-C can be used as a biochemical marker in the differential
      diagnosis of rheumatic and congenital HVD. As the oxidant and antioxidant systems
      were found to be in equilibrium in rheumatic and congenital HVD, oxidative stress
      can be thought not to have a marked role in the etiopathogenesis of rheumatic HVD
      during childhood.

PMID- 23531873
TI  - Relationship of paraoxonase-1, malondialdehyde and mean platelet volume with
      markers of atherosclerosis in familial Mediterranean fever: an observational
      study.
AB  - OBJECTIVE: There are many studies demonstrating deteriorated ventricle and
      endothelium functions in familial Mediterranean fever (FMF) patients. As FMF is
      an autoinflammatory disease with an ongoing inflammatory activity and
      inflammation plays an important role in the development and progression of
      atherosclerosis in some of the rheumatic diseases, we aimed to investigate the
      early markers of atherosclerosis in patients with FMF by the measurements of
      serum paraoxonase-1 (PON-1) activity, mean platelet volume (MPV) and
      malondialdehyde (MDA) level. METHODS: This study is a cross-sectional,
      observational study. Forty consecutive patients with FMF and twenty healthy
      volunteers were selected to form the study population. The diagnosis of FMF was
      based on Tel-Hashomer criteria. Serum PON-1 activity, MPV and MDA level were
      determined to examine their association with FMF. Student's t-test, Mann-Whitney
      U test, Pearson correlation analysis were used for statistical analysis. RESULTS:
      The mean PON-1 activity in FMF patients was significantly lower than in the
      healthy population (141.46+/-38.29 vs. 179.62+/-10.73 U/l, p<0.01). Serum MDA
      levels were the same between the groups (1.08+/-0.66 vs. 1.08+/-0.33 nmol/mL,
      p=0.99). MPV was higher in FMF patients than in the control l group (8.87+/-0.99
      vs. 8.22+/-0.45 fl, p=0.04). PON, MPV and MDA levels were the same in FMF
      patients with acute attack and attack -free period. CONCLUSION: Our results show
      that PON-1 activity is lower in patients with FMF. Reduced PON-1 activity and
      increased MPV, independent of the oxidative stress status of these patients, may
      lead to increased atherosclerotic propensity in FMF.

PMID- 23531874
TI  - A kinase-independent biological activity for insulin growth factor-1 receptor
      (IGF-1R) : implications for inhibition of the IGF-1R signal.
AB  - It has been demonstrated that epidermal growth factor receptor (EGFR) can have
      kinase independent activity. EGFR kinase-independent function maintains
      intracellular glucose levels via sodium glucose transporter protein 1 (SGLT1) and
      supports cell survival. It is plausible that this phenomenon can apply to other
      receptor tyrosine kinases. We found that transfection of insulin-like growth
      factor receptor (IGF-1R) siRNA into HEK293 (human embryonic kidney) and MCF7
      (metastatic breast cancer) cells result in decreased intracellular glucose
      levels, whereas treatment with an IGF-1R tyrosine kinase inhibitor OSI-906 did
      not affect intracellular glucose levels. In addition, IGF-1R interacted with
      SGLT1 in a manner similar to that previously reported with EGFR. The combination
      of IGF-1R siRNA and OSI-906 resulted in decreased viability of HEK293 and MCF7
      cell lines compared to either agent alone. Collectively, these experiments
      suggest that IGF-1R, has kinase-independent biologic functions and provide a
      rationale for combining anti-IGF-1R antibodies or siRNA and IGF-1R small molecule
      inhibitors.

PMID- 23531875
TI  - Tuberculosis in CBA/J mice.
AB  - Tuberculosis (TB) develops in 5% to 10% of people infected with Mycobacterium
      tuberculosis (M.tb), but we do not understand how TB develops. CBA/J mice may
      model these events, as sick mice share features with TB patients, including
      weight loss, M.tb growth, extensive granulomatous infiltrates, neutrophils,
      necrosis, and fibrosis. Here, M.tb-infected CBA/J mice were categorized
      clinically: those with no signs or those with 10% weight loss to determine
      whether clinical state was associated with lung lesions. The type and
      distribution of infiltrates (granulomatous with lymphoid aggregates and scattered
      neutrophils) were similar in mice with weight loss and in mice with no signs. The
      amount of infiltration and neutrophil foci were higher in mice with weight loss
      than in mice with no clinical signs. Necrosis and fibrosis were only identified
      in mice that lost weight. Our results suggest that CBA/J mice may be useful to
      determine if and how neutrophils contribute to TB disease progression in mouse
      models. 

PMID- 23531876
TI  - Pressure and temperature dependent photolysis of glyoxal in the 355-414 nm
      region: evidence for dissociation from multiple states.
AB  - The photolysis of glyoxal has been investigated in the 355-414 nm region by dye
      laser photolysis coupled with cavity ring-down spectroscopy. Absolute quantum
      yields of HCO, PhiHCO, were determined using the reaction of chlorine atoms with
      formaldehyde as an actinometer. The dependence of the quantum yield on pressure
      was investigated in 3-400 Torr of nitrogen buffer gas and at four temperatures:
      233 K, 268 K, 298 K and 323 K. For 355 nm <= lambda < 395 nm the HCO quantum
      yield is pressure dependent with linear Stern-Volmer (SV) plots (1/PhiHCO vs.
      pressure). The zero pressure quantum yield, obtained by extrapolation of the SV
      plots, rises from 1.6 to 2 between 355 and 382 nm and remains at 2 up to 395 nm.
      For lambda >= 395 nm PhiHCO shows a stronger pressure dependence and non-linear
      SV plots, compatible with formation of HCO by dissociation from two electronic
      states of glyoxal with significantly different lifetimes. These observations are
      used to develop a mechanism for the photolysis of glyoxal over the wavelength
      range studied.

PMID- 23531877
TI  - Characterization of the depth distribution of Ca, Fe and Zn in skin samples,
      using synchrotron micro-x-ray fluorescence (SMUXRF) to help quantify in-vivo
      measurements of elements in the skin.
AB  - In vivo monitoring of trace and biometals in skin is normally quantified using
      phantoms that assume a constant elemental distribution within the skin. Layered
      calibration skin phantoms could potentially improve the reliability of in vivo
      calibration skin phantoms by better representing the actual in vivo distribution.
      This work investigates the micro-distribution of iron, calcium and zinc in
      prepared human skin samples taken from a number of locations on the body. Slices
      (orientation running from the skin surface into the dermis) were extracted from
      18 formalin-fixed necropsy samples and scanned using the micro-XRF setup at the
      VESPERS beamline (Canadian Light Source). Elemental surface maps were produced
      using a 6*6 MUm(2) beam in steps of 10 MUm. Microscope images of histology slides
      were obtained for comparison. Statistically significant differences (p<0.01) were
      noted between the epidermal and dermal layers of skin for the elements examined
      (Ca, Fe and Zn), demonstrating the ability to clearly distinguish elemental
      content in each layer. Iron was consistently noted at the epidermal/dermal
      boundary. These results would indicate that when using phantoms to quantify
      elemental levels measured in the skin, note should be taken of the appropriate
      depth distribution.

PMID- 23531878
TI  - Follicular helper T cells: new insights into mechanisms of autoimmune diseases.
AB  - BACKGROUND: Autoimmune diseases (such as systemic lupus erythematosus, rheumatoid
      arthritis, type 1 diabetes, etc) are characterized by the production of
      autoantibodies against one's own cell components, resulting in the dysfunction of
      normal organs. At present, therapies for autoimmune diseases involve a variety of
      nonspecific antiinflammatory and immunosuppressive agents with significant side
      effects. Current studies have suggested that the germinal center (GC) may be the
      pathogenic hot spot for the production of autoantibodies in autoimmune disease.
      Events occurring in the GC-such as the selection of high-affinity B cells,
      proliferation of B cells, and differentiation of B cells into plasma cells-all
      depend on T cells. Follicular helper T (Tfh) cells are a recently identified T
      cell subset, named for their location in GCs. Tfh cells are characterized by
      their signature transcription factor (B-cell lymphoma 6), surface molecules (CD40
      ligand, chemokine [C-X-C] receptor 5, inducible T-cell costimulator, programmed
      cell death protein-1, etc), and cytokines (interleukin [IL]-21, IL-6, IL-10,
      etc). Through these signals, Tfh cells help B cells form GCs and drive B cells to
      differentiate into memory B cells and plasma cells that produce antibodies.
      However, uncontrolled generation of Tfh cells in the GCs or peripherals could
      lead to autoimmunity. Recent studies from our group and others have shown that
      Tfh cells are expanded in the peripheral blood of patients and in the lymphoid
      tissues of mice with lupus or rheumatoid arthritis and play an important role in
      promoting pathogenic autoantibody production. METHODS: In this review, we
      summarize the latest immunologic findings regarding the characteristics and
      development of Tfh cells, their relation to other CD4(+) T-cell subsets, and the
      function of Tfh cells in normal immune response and autoimmune diseases.
      CONCLUSION: A clear understanding of the mechanisms of Tfh cell-mediated immunity
      and pathology may lead to the development of novel therapeutic targets in
      autoimmune diseases.

PMID- 23531879
TI  - Planar parathyroid localization scintigraphy: a comparison of subtraction and 1-,
      2- and 3-h washout protocols.
AB  - INTRODUCTION: With the advent of minimally invasive surgery to treat
      hyperparathyroidism, preoperative imaging of parathyroid glands has become
      routine practice. Scintigraphy and ultrasound are the two most common imaging
      techniques. Despite this, published sensitivities for scintigraphy vary
      enormously, and there is a multitude of protocols performed. This investigation
      compares the accuracies of planar subtraction and multiple washout images in the
      same group of patients. METHODS: We followed up 190 consecutive patients who
      underwent a combined subtraction and washout scintigraphy protocol and compared
      the results against surgical outcomes, taken as the gold standard. Technetium-99m
      sestamibi images were acquired at 5 min and at 1, 2 and 3 h, followed by a
      technetium-99m pertechnetate image for subtraction. Sixty-four of these patients
      also underwent ultrasound imaging for localization. The relative value of each
      part of the protocol in localizing adenomas was compared. RESULTS: The overall
      accuracy of this combined protocol for correct localization of both the side and
      axial level of parathyroid adenomas was 81% (90% when considering the side of the
      adenoma alone). Of all the nuclear medicine images produced, subtraction was the
      most useful. The 1 and 2 h washout images were comparable but the 3 h image added
      no value. The accuracy of ultrasound imaging was 55% for the side and pole and
      60% for the side of the adenoma. CONCLUSION: For optimal accuracy a planar
      parathyroid localization protocol should include subtraction and at least one
      washout image between 1 and 2 h after injection.

PMID- 23531882
TI  - Parkin promotes cell survival via linear ubiquitination.

PMID- 23531880
TI  - YY1 controls Igkappa repertoire and B-cell development, and localizes with
      condensin on the Igkappa locus.
AB  - Conditional knock-out (KO) of Polycomb Group (PcG) protein YY1 results in pro-B
      cell arrest and reduced immunoglobulin locus contraction needed for distal
      variable gene rearrangement. The mechanisms that control these crucial functions
      are unknown. We deleted the 25 amino-acid YY1 REPO domain necessary for YY1 PcG
      function, and used this mutant (YY1DeltaREPO), to transduce bone marrow from YY1
      conditional KO mice. While wild-type YY1 rescued B-cell development, YY1DeltaREPO
      failed to rescue the B-cell lineage yielding reduced numbers of B lineage cells.
      Although the IgH rearrangement pattern was normal, there was a selective impact
      at the Igkappa locus that showed a dramatic skewing of the expressed Igkappa
      repertoire. We found that the REPO domain interacts with proteins from the
      condensin and cohesin complexes, and that YY1, EZH2 and condensin proteins co
      localize at numerous sites across the Ig kappa locus. Knock-down of a condensin
      subunit protein or YY1 reduced rearrangement of Igkappa Vkappa genes suggesting a
      direct role for YY1-condensin complexes in Igkappa locus structure and
      rearrangement.

PMID- 23531883
TI  - Uncertainty concerning the 4-field box technique for Stage-IB2 carcinoma of the
      uterine cervix.
AB  - Radiation Therapy (RT) plays a pivotal role in the curative approach for
      carcinoma of the cervix. Inspite of the emergence of various new conformal
      techniques in RT, conventional techniques still hold vital importance. Majority
      of the patients worldwide are treated with 2D-RT techniques. 2D-RT techniques
      have been proven to be non-inferior and simpler in comparison to 3D-RT in the
      context of carcinoma of the cervix. However, inadequate target volume coverage
      with improper portal design can preclude the chances of cure. We demonstrate the
      need for abolishing guesswork in terms of target volume determination through the
      example of a patient's sagittal magnetic resonance image showing a case of the
      retroverted uterus which would have been likely to be missed from the treatment
      portals if they were designed using definitions based on bony landmarks.

PMID- 23531881
TI  - Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and
      deleterious crossover.
AB  - The error-free DNA damage tolerance (DDT) pathway is crucial for replication
      completion and genome integrity. Mechanistically, this process is driven by a
      switch of templates accompanied by sister chromatid junction (SCJ) formation.
      Here, we asked if DDT intermediate processing is temporarily regulated, and what
      impact such regulation may have on genome stability. We find that persistent DDT
      recombination intermediates are largely resolved before anaphase through a G2/M
      damage checkpoint-independent, but Cdk1/Cdc5-dependent pathway that proceeds via
      a previously described Mus81-Mms4-activating phosphorylation. The Sgs1-Top3- and
      Mus81-Mms4-dependent resolution pathways occupy different temporal windows in
      relation to replication, with the Mus81-Mms4 pathway being restricted to late
      G2/M. Premature activation of the Cdk1/Cdc5/Mus81 pathway, achieved here with
      phosphomimetic Mms4 variants as well as in S-phase checkpoint-deficient genetic
      backgrounds, induces crossover-associated chromosome translocations and
      precocious processing of damage-bypass SCJ intermediates. Taken together, our
      results underscore the importance of uncoupling error-free versus erroneous
      recombination intermediate processing pathways during replication, and establish
      a new paradigm for the role of the DNA damage response in regulating genome
      integrity by controlling crossover timing.

PMID- 23531885
TI  - Does combined cognitive training and physical activity training enhance cognitive
      abilities more than either alone? A four-condition randomized controlled trial
      among healthy older adults.
AB  - Cognitive training and aerobic training are known to improve cognitive functions.
      To examine the separate and combined effects of such training on cognitive
      performance, four groups of healthy older adults embarked on a 4 months cognitive
      and/or mild aerobic training. A first group [n = 33, mean age = 80 (66-90)]
      engaged in cognitive training, a second [n = 29, mean age = 81 (65-89)] in mild
      aerobic training, a third [n = 29, mean age = 79 (70-93)] in the combination of
      both, and a fourth [n = 31, mean age = 79 (71-92)] control group engaged in book
      reading activity. The outcome was a well-validated multi-domain computerized
      cognitive evaluation for older adults. The results indicate that, when compared
      to older adults who did not engage in cognitive training (the mild aerobic and
      control groups) older adults who engaged in cognitive training (separate or
      combined training groups) showed significant improvement in cognitive performance
      on Hand-Eye Coordination, Global Visual Memory (GVM; working memory and long-term
      memory), Speed of Information Processing, Visual Scanning, and Naming. Indeed,
      individuals who did not engage in cognitive training showed no such improvements.
      Those results suggest that cognitive training is effective in improving cognitive
      performance and that it (and not mild aerobic training) is driving the
      improvement in the combined condition. Results are discussed in terms of the
      special circumstances of aerobic and cognitive training for older adults who are
      above 80 years of age.

PMID- 23531886
TI  - Public Health Pharmacogenomics and the Design Principles for Global Public Goods 
      Moving Genomics to Responsible Innovation.

PMID- 23531887
TI  - ACSM's clinician profile, 10.4. Elizabeth A. Joy, MD, MPH, FACSM.

PMID- 23531884
TI  - Global hyper-synchronous spontaneous activity in the developing optic tectum.
AB  - Studies of patterned spontaneous activity can elucidate how the organization of
      neural circuits emerges. Using in vivo two-photon Ca(2+) imaging, we studied
      spatio-temporal patterns of spontaneous activity in the optic tectum of Xenopus
      tadpoles. We found rhythmic patterns of global synchronous spontaneous activity
      between neurons, which depends on visual experience and developmental stage. By
      contrast, synchronous spontaneous activity between non-neuronal cells is mediated
      more locally. To understand the source of the neuronal spontaneous activity,
      input to the tectum was systematically removed. Whereas removing input from the
      visual or mechanosensory system alone had little effect on patterned spontaneous
      activity, removing input from both systems drastically altered it. These results
      suggest that either input is sufficient to maintain the intrinsically generated
      spontaneous activity and that patterned spontaneous activity results from input
      from multisensory systems. Thus, the amphibian midbrain differs from the
      mammalian visual system, whose spontaneous activity is controlled by retinal
      waves.

PMID- 23531888
TI  - Rhabdo redux: "Don't know much about history".

PMID- 23531890
TI  - Sports concussion expertise requires integrating complementary viewpoints.

PMID- 23531891
TI  - Omega-3 polyunsaturated fatty acids and concussions: treatment or not?

PMID- 23531892
TI  - Actovegin--Cutting-edge sports medicine or "voodoo" remedy?
AB  - Actovegin is a deproteinized serum extract of bovine origin, and in recent years
      it has been used widely in treating sport injuries with many anecdotal reports of
      success. However, the use of Actovegin in sport medicine has caused a substantial
      amount of controversy, especially concerning its supposed oxygen-enhancing
      capacity and an anecdotal belief that its use can increase an athlete's
      performance. In 2009, a sports physician was arrested with this "performance
      enhancing drug," while an editorial in a sports medicine journal strongly
      questioned the evidence base for using this drug for acute muscle injury. There
      is also a report that suggested that Actovegin might have induced anaphylactic
      shock in a cyclist. In this review, we have systematically examined the current
      evidence on Actovegin. Its mechanism of action, clinical evidence, legal status
      with sports governing bodies, and its potential role in sport injuries will be
      discussed.

PMID- 23531893
TI  - Evaluating the athlete's claim of an unintentional positive urine drug test.
AB  - During a urine drug testing program, an athlete may make a claim that the results
      of a positive test have arisen from factors that were out of his or her control,
      and therefore, he or she should not be held responsible for the results. Some of
      these claims may include classic claims of passive inhalation of marijuana smoke
      or ingestion of poppy seeds leading to positive tests. In addition, with the
      proliferation of nutritional supplements on the market, many athletes claim that
      they accidentally ingested a banned substance contained in one of these. It is
      important that any sports medicine physician involved with sports drug testing be
      informed of the data that either support or refute these claims and that he or
      she contribute to a program wherein adequate education and policy establishment
      help to limit the likelihood of such claims. This article will review the data to
      help address these claims.

PMID- 23531894
TI  - Exercise-induced asthma: nutritional management.
AB  - Exercise-induced asthma (EIA) refers to the transient narrowing of the airways
      following strenuous exercise in asthmatic and otherwise healthy individuals.
      Despite the heterogeneous treatment options for patients with EIA, there remains
      a substantial burden of unaddressed disease, even with optimal treatment.
      Epidemiological studies indicate that patients frequently resort to complementary
      and alternative therapies while being treated for asthma and other chronic health
      conditions. There is now convincing evidence that many dietary factors such as
      increased omega-3 polyunsaturated fatty acids, antioxidant intake and caffeine,
      and a sodium-restricted diet can reduce the severity of EIA. It is important that
      these dietary therapies be safe, effective, and likely to be used by individuals
      with EIA. This review will critically examine whether dietary modification
      represents a beneficial intervention for asthmatic individuals with EIA.

PMID- 23531895
TI  - Carbohydrate-protein intake and recovery from endurance exercise: is chocolate
      milk the answer?
AB  - Postexercise carbohydrate intake has been shown to augment recovery from heavy
      aerobic exercise. The effects of carbohydrate and protein coingestion (CHO + Pro)
      have been investigated more recently, including the potential influences of
      chocolate milk. Some studies report that CHO + Pro beverages (including chocolate
      milk) enhance subsequent exercise performance versus carbohydrate beverages,
      although others have reported no positive effects. The putative efficacy of CHO +
      Pro could be due to influences on glycogen resynthesis, protein turnover,
      rehydration, attenuations in muscle disruption, or perhaps a combination of these
      factors. However, there are inconsistencies in the literature regarding the
      effects of CHO + Pro on these factors, and the mechanisms explaining potential
      influences of CHO + Pro are not defined clearly. Further research is required to
      address these limitations, but present evidence suggests that CHO + Pro beverages
      may positively influence recovery under some exercise conditions, and chocolate
      milk is likely a good recovery beverage for lactose-tolerant endurance athletes.

PMID- 23531896
TI  - Review of the role of exercise in improving quality of life in healthy
      individuals and in those with chronic diseases.
AB  - The use of exercise for improving health has been the subject of research for
      several decades. Studies have shown unequivocally that exercise is beneficial for
      preventing and/or treating numerous medical conditions. With the U.S. population
      increasing in age, use of exercise to ameliorate the effect of illnesses related
      to aging is therefore of great potential value. Despite this information, most
      members of the population do not incorporate physical activity into their daily
      routine. Because aging often is associated with diminished quality of life, we
      reviewed the literature to assess whether exercise is of value in maintaining a
      person's functional capacity as he or she ages. Available data suggest a positive
      relationship between higher levels of fitness and higher functional
      state/improved quality of life, both in healthy individuals and in those
      experiencing specific ailments commonly seen in an aging population.

PMID- 23531897
TI  - Cost-effectiveness of exercise is medicine.
AB  - There is considerable scientific evidence documenting the health benefits
      associated with a physically active lifestyle. Despite this evidence, a high
      level of physical inactivity in many countries is placing a considerable burden
      on health care budgets. Country-specific estimates of the economic costs
      attributable to physical inactivity range from 1.2% to 2.5% of total annual
      health care expenditures. Despite the existence of effective physical activity
      interventions, their deployment in primary care has been limited. The results
      from a limited number of studies conducted in primary care settings demonstrate
      that the promotion of physical activity may be a cost-effective approach. Future
      studies of physical activity intervention are encouraged to contribute important
      cost-effectiveness analysis information to the emerging evidence in this area.

PMID- 23531898
TI  - Dog ownership and dog walking to promote physical activity and health in
      patients.
AB  - Lack of physical activity is a significant risk factor for many chronic diseases
      and conditions and is associated with significant medical costs. Approximately
      half of adults and more than a third of adolescents and youth in the United
      States do not achieve recommended levels of physical activity. Effective
      population-level strategies are needed to promote activities that are practical,
      accessible, and sustainable and that can reach a large proportion of the
      population. Dog walking may be such a strategy. Walking is popular, easy, and
      sustainable and has a low risk of injury. Owning dogs confers many health
      benefits, and dog walking, in particular, can help promote physical activity and
      improve health. Physicians and other health care providers can play a unique and
      integral role in promoting physical activity among patients by recommending dog
      walking both to dog owners and to non-dog owners as a purposeful, enjoyable, and
      sustainable form of regular physical activity.

PMID- 23531899
TI  - A good walk spoiled: on the disappearance of golf as an active sport in America.
AB  - During the past 60 years, there has been a major transition in the way golf is
      played in America. Its potential as exercise largely has been negated by the
      increase in motorized golf cart usage to approximately two of every three rounds
      played in this country. Accidents in golf carts have increased rapidly, which, by
      making the sport more dangerous, will likely bring future regulations.
      Consequently, playing golf has gradually become more of a public health threat
      than a benefit. The motorized cart also has resulted in an almost doubling of the
      size of golf courses, which now occupy a large amount of the built environment
      designated for activity. These changes are a major loss to society, portend
      future problems, and call for the sport to reevaluate its current model.

PMID- 23531900
TI  - Proceedings from the Ice Hockey Summit on Concussion: a call to action.
AB  - OBJECTIVE: The objective of this proceeding is to integrate the concussion in
      sport literature and sport science research on safety in ice hockey to develop an
      action plan to reduce the risk, incidence, severity, and consequences of
      concussion in ice hockey. METHODS: A rationale paper outlining a collaborative
      action plan to address concussions in hockey was posted for review two months
      prior to the Ice Hockey Summit: Action on Concussion. Focused presentations
      devoted specifically to concussion in ice hockey were presented during the Summit
      and breakout sessions were used to develop strategies to reduce concussion in the
      sport. This proceedings and a detailed scientific review (a matrix of solutions)
      were written to disseminate the evidence-based information and resulting
      concussion reduction strategies. The manuscripts were reviewed by the authors,
      advisors and contributors to ensure that the opinions and recommendations reflect
      the current level of knowledge on concussion in hockey. RESULTS: Six components
      of a potential solution were articulated in the Rationale paper and became the
      topics for breakout groups that followed the professional, scientific lectures.
      Topics that formed the core of the action plan were: metrics and databases;
      recognizing, managing and return to play; hockey equipment and ice arenas;
      prevention and education; rules and regulations; and expedient communication of
      the outcomes. The attendees in breakout sessions identified action items for each
      section. The most highly ranked action items were brought to a vote in the open
      assembly, using an Audience Response System (ARS). The strategic planning process
      was conducted to assess: Where are we at?; Where must we get to?; and What
      strategies are necessary to make progress on the prioritized action items?
      CONCLUSIONS: Three prioritized action items for each component of the solution
      and the percentage of the votes received are listed in the body of this
      proceeding.

PMID- 23531901
TI  - A rapid method for the assessment of the surface group density of carboxylic acid
      functionalized polystyrene microparticles.
AB  - Particle-based assays are becoming versatile analytical tools due to their cost
      effectiveness, speed, straightforward and diverse functionalization chemistries,
      especially when polystyrene particles are used. The introduction of functional
      groups (-COOH, -NH2, etc.) to the surface of such polystyrene particles promotes
      their application in bioanalytics. However, the traditional method to determine
      the amount of surface carboxylate groups is conductivity titration, which is
      usually time- and resources-consuming and discontinuous. Here, we synthesized
      polystyrene microparticles with different contents of carboxylate groups, and
      then investigated a simpler and potentially continuous approach to determine the
      amount of surface carboxylate groups by Zeta potential measurements. The results
      were compared to the traditional titration method and to actual coupling
      efficiencies of the functionalized particles with a model oligonucleotide probe
      as determined by flow cytometry. All quantification methods revealed good
      agreement.

PMID- 23531902
TI  - Considerations for using bacteriophages for plant disease control.
AB  - The use of bacteriophages as an effective phage therapy strategy faces
      significant challenges for controlling plant diseases in the phyllosphere. A
      number of factors must be taken into account when considering phage therapy for
      bacterial plant pathogens. Given that effective mitigation requires high
      populations of phage be present in close proximity to the pathogen at critical
      times in the disease cycle, the single biggest impediment that affects the
      efficacy of bacteriophages is their inability to persist on plant surfaces over
      time due to environmental factors. Inactivation by UV light is the biggest factor
      reducing bacteriophage persistence on plant surfaces. Therefore, designing
      strategies that minimize this effect are critical. For instance, application
      timing can be altered: instead of morning or afternoon application, phages can be
      applied late in the day to minimize the adverse effects of UV and extend the time
      high populations of phage persist on leaf surfaces. Protective formulations have
      been identified which prolong phage viability on the leaf surface; however, UV
      inactivation continues to be the major limiting factor in developing more
      effective bacteriophage treatments for bacterial plant pathogens. Other
      strategies, which have been developed to potentially increase persistence of
      phages on leaf surfaces, rely on establishing non-pathogenic or attenuated
      bacterial strains in the phyllosphere that are sensitive to the phage(s) specific
      to the target bacterium. We have also learned that selecting the correct phages
      for disease control is critical. This requires careful monitoring of bacterial
      strains in the field to minimize development of bacterial strains with resistance
      to the deployed bacteriophages. We also have data that indicate that selecting
      the phages based on in vivo assays may also be important when developing use for
      field application. Although bacteriophages have potential in biological control
      for plant disease control, there are major obstacles, which must be considered.

PMID- 23531903
TI  - [Mediastinal widening].

PMID- 23531905
TI  - [Safety and feasibility of vacuum-assisted biopsy by ultrasound-guidance for non
      distinctive soft-tissue lesions].
AB  - BACKGROUND: Only the exact pretherapeutical, histopathological diagnosis of non
      distinctive soft tissue tumours leads to adequate therapy. Next to the
      standardized incisional biopsy, current needle biopsy techniques are limited by
      the small size of the tissue samples and error rate. This study was performed to
      explore whether the ultrasound-guidance can support the vacuum-assisted biopsy of
      soft tissue tumors in technical safety. MATERIALS AND METHODS: Between 2004-2006,
      116 patients with non-distinctive soft tissue tumours underwent ultrasound-guided
      vacuum-assisted biopsy (uVAB). The results were compared to a cohorte with
      standardized incisional biopsy (IB). RESULTS: The procedure was successful in 115
      patients (success rate: 99,1%). Rate of complications was 4,3% (n=5/116). This
      closed biopsy technique was performed as an outpatient procedure with local
      anaesthesia. Diagnosis by uVAB was comparable to the control group (concordance
      of entity in 94,7%, grading: 89,3%, sensitivity: 93,5%, specificity: 100%,
      accuracy: 96,2%). CONCLUSION: Ultrasound-guided the vacuum-assisted biopsy is a
      safe procedure for soft tissue tumors. The results of this minimal invasive
      method are comparable to open the gold-standardized incisional biopsy.

PMID- 23531906
TI  - [Lumbar spinal stenosis: diagnosis and conservative treatment].
AB  - Lumbar Spinal Stenosis is a typical disease of the elderly patient that mainly
      originates in degenerative multisegmental changes of the lumbar vertebral column.
      The classical symptom of pain irradiation into the legs whilst walking and relief
      with standing is similar to peripheral arterial disease presentation but differs
      in the sense that symptoms can be triggered through lumbar extension and relieved
      with lumbar flexion whereas arterial disease is correlated with pathological
      arteriovascular findings. Diagnosis is usually confirmed through magnetic
      resonance imaging (MRI) and response to conservative treatment (analgetics,
      physiotherapy, epidural injections) is usually good in the majority of cases.
      Only a minority of about 20% of all cases show progressive disease and may
      necessitate surgical interventions.

PMID- 23531907
TI  - [Indolent lymphomas: classification, clinical presentation and treatment]].
AB  - The malignant lymphomas comprise a heterogeneous group of neoplastic diseases of
      the lymphatic system. In the WHO classification 70 different entities are
      subdivided. Each type of lymphoma is defined as a disease with specific clinical
      characteristics, as well as morphological, immunophenotypic and genetic
      characteristics. The indolent lymphomas include follicular lymphoma, marginal
      zone lymphoma, Lymphoplasmacytic lymphoma, small cell lymphocytic lymhoma/chronic
      lymphocytic leukemia, prolymphocytic leukemia and hairy cell leukemia. Indolent
      lymphomas are characterized by slow growth and a chronic course of the disease.
      Antibody-based therapies, have significantly improved the prognosis, nevertheless
      there is no curative treatment. Watch and wait is still an reasonable option in
      asymptomatic patients. The goal of therapy has been to maintain the best quality
      of life. and to avoid late toxicities. The following review presents the current
      treatment options.

PMID- 23531908
TI  - [Hirschsprung disease].

PMID- 23531909
TI  - [Is procalcitonin determination for control of antibiotic therapy in acute
      respiratory infections of value?].

PMID- 23531910
TI  - [The brain as master of the heart].
AB  - We admitted a 42 year old woman with clinical signs of shock, coma, and ecg
      changes consistent with a ST elevation myocardial infarction to percutaneous
      coronary intervention. Normal coronary arteries were found. Due to the comatose
      state a cranial computed tomography scan was performed, where a subarachnoid
      hemorrhage was detected. We discuss the difficulty of diagnosing a subarachnoid
      hemorrhage, the pathophysiological cause of cardiac damage and ecg changes in
      acute neurological disease, and the differential diagnosis of ST elevation in the
      ecg.

PMID- 23531911
TI  - [Whiplash injury: effectiveness of activating initial consultation and physical
      therapy are low].

PMID- 23531912
TI  - [Empirical treatment of chest pain with esomeprazole].

PMID- 23531916
TI  - Tibial cleaning method for cemented total knee arthroplasty: An experimental
      study.
AB  - BACKGROUND: The survival rate of cemented knee prosthesis depends among other
      factors on optimal cement-bone contact, nevertheless no standard exists for
      cementing technique of tibial components. The aim of this study was to determine
      which tibial surface preparation technique leads to the best bone-cement contact.
      MATERIALS AND METHODS: HUMAN TIBIAL PLATEAU SPECIMENS WERE CLEANED IN FOUR
      DIFFERENT WAYS BEFORE CEMENTING: a) no cleaning, b) manual syringe irrigation, c)
      fracture brush cleaning, and d) pulsatile jet-lavage. The specimens were cut into
      transverse sections and the bone cement contact distance was calculated for every
      10 mm and the cement penetration depth was measured. Both values were
      statistically analyzed (ANOVA). RESULTS: The longest bone-cement contact (62 mm)
      was seen after PJL, the shortest (10.6 mm) after no cleaning at all. The deepest
      cement penetration (4.1 mm) again was seen after PJL, the least (0.7 mm) after no
      cleaning. Statistically, PJL yielded the longest bone-cement contact and deepest
      cement penetration. CONCLUSION: The results supports the use of pulsatile jet
      lavage before cementing tibial components in knee arthroplasty.

PMID- 23531917
TI  - Polyphenols from the Mediterranean herb rosemary (Rosmarinus officinalis) for
      prostate cancer.
AB  - The Mediterranean diet is rich in fruits and vegetables and has been associated
      with a variety of health benefits including cancer prevention. One aspect of the
      diet that has not received enough attention is Mediterranean herbs. Specifically,
      rosemary and its polyphenolic diterpenes (carnosic acid and carnosol) are known
      to possess anti-oxidant activity that may be beneficial for cancer control.
      Herein, we describe the in vitro and in vivo studies carried out towards
      understanding the molecular mechanisms of carnosic acid and carnosol leading to
      inhibition of prostate cancer. The reported findings suggest that these
      polyphenols target multiple signaling pathways involved in cell cycle modulation
      and apoptosis. Further work is required to understand its potential for health
      promotion and potential drug discovery for prostate cancer chemoprevention.

PMID- 23531919
TI  - Comparison of anti-mullerian hormone and antral follicle count for assessment of
      ovarian reserve.
AB  - AIM: This study aims to compare the efficacy of AFC and AMH, as markers for
      ovarian reserve. MATERIALS AND METHODS: 75 patients with PCO (polycystic ovaries)
      undergoing IVF were randomized with 75 non-PCO patients. On day 3, volume of
      ovary was acquired, ovarian volume was defined by VOCAL, and Sono AVC was used to
      count the number of antral follicles. Sum total of antral follicles in both
      ovaries was taken as total antral follicle count (AFC). AMH was measured on the
      same day. Long agonist protocol with recombinant FSH (rFSH) was used for IVF
      stimulation till at least two follicles of 18 mm were seen. hCG 10,000 iu was
      given and ovum pick up was done after 34-35 h. Primary end point was number of
      follicles >12 mm seen on day of hCG. Final end point was number of ova retrieved
      on ovum pick up. Correlation of AFC and AMH was checked for both end points and
      with each other. RESULTS: Correlation of AFC and follicles >12 mm on day of hCG
      in PCO group is 0.56 and non-PCO group is 0.63,(1) and for AMH and follicles >12
      mm on day of hCG in PCO group is 0.42 and non-PCO group is 0.47. Correlation of
      AFC with number of ova retrieved on OPU in PCO group is 0.44 and for non-PCO
      group is 0.50. The value for AMH is 0.39 in PCO and 0.43 for non-PCO group.
      Comparing correlation of AFC and AMH for primary end point in PCO group has 'z'
      value 1.11(onetailed significance 0.1335, twotailed significance 0.267) and in
      non-PCO group comparison shows a 'z' value of 1.39 (one tailed significance
      0.0823, two-tailed significance 0.1645). Therefore in both groups, AFC and AMH
      correlates with total number of follicles >12 mm on day of hCG, but both AFC and
      AMH have independent significance. Comparing correlation of AFC and AMH with
      number of ova retrieved on OPU, in non-PCO group has 'z' value of 0.54(one tailed
      0.2946, two-tailed 0. 5892). In PCO group, this comparison shows, 'z' value of
      0.36(one tailed 0.3594, two tailed 0.7188). CONCLUSION: AFC and AMH correlate
      with each other but have independent significance for estimating follicles >12 mm
      on day of hCG. For ova retrieved on OPU, in PCO group, AMH and AFC have similar
      significance. In non-PCO, AMH may increase accuracy of estimation of number of
      ova retrieved on OPU over AFC, but difference is not significant. AFC only may
      suffice for estimation of number of ova retrieved on OPU for all practical
      purposes.

PMID- 23531918
TI  - Neuromagnetic activation following active and passive finger movements.
AB  - The detailed time courses of cortical activities and source localizations
      following passive finger movement were studied using whole-head
      magnetoencephalography (MEG). We recorded motor-related cortical magnetic fields
      following voluntary movement and somatosensory-evoked magnetic fields following
      passive movement (PM) in 13 volunteers. The most prominent movement-evoked
      magnetic field (MEF1) following active movement was obtained approximately 35.3
      +/- 8.4 msec after movement onset, and the equivalent current dipole (ECD) was
      estimated to be in the primary motor cortex (Brodmann area 4). Two peaks of MEG
      response associated with PM were recorded from 30 to 100 msec after movement
      onset. The earliest component (PM1) peaked at 36.2 +/- 8.2 msec, and the second
      component (PM2) peaked at 86.1 +/- 12.1 msec after movement onset. The peak
      latency and ECD localization of PM1, estimated to be in area 4, were the same as
      those of the most prominent MEF following active movement. ECDs of PM2 were
      estimated to be not only in area 4 but also in the supplementary motor area (SMA)
      and the posterior parietal cortex (PPC) over the hemisphere contralateral to the
      movement, and in the secondary somatosensory cortex (S2) of both hemispheres. The
      peak latency of each source activity was obtained at 54-109 msec in SMA, 64-114
      msec in PPC, and 84-184 msec in the S2. Our results suggest that the magnetic
      waveforms at middle latency (50-100 msec) after PM are different from those after
      active movement and that these waveforms are generated by the activities of
      several cortical areas, that is, area 4 and SMA, PPC, and S2. In this study, the
      time courses of the activities in SMA, PPC, and S2 accompanying PM in humans were
      successfully recorded using MEG with a multiple dipole analysis system.

PMID- 23531920
TI  - Age differences in eyewitness memory for a realistic event.
AB  - OBJECTIVES: To better understand the effects of misinformation on eyewitnesses of
      different ages, older and younger adults experienced an event under intentional
      and incidental learning conditions in a naturalistic experiment using multiple
      memory tests. METHOD: Following exposure to the event, which was a brief
      interruption of a group testing session, participants completed several memory
      tests. For half of the participants, misinformation was embedded in the first
      cued recall test. On subsequent free recall and cued recall tests, basic scores
      and misinformation-based memory errors were examined. RESULTS: As expected,
      younger adults had higher recall scores than older adults. Older and younger
      adults made the same number of misinformation errors in free recall and in cued
      recall with intentional learning. However, in the incidental condition, younger
      adults made more misinformation errors likely due to the information processing
      strategies they employed after incidental learning. DISCUSSION: Misinformation
      effects were quite strong, even with a realistic scene and intentional learning.
      Older adult suggestibility was no worse than that of younger adults. When
      misinformation was combined with incidental learning, younger adults may have
      used strategic processing to encode misinformation to their detriment.

PMID- 23531921
TI  - Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor
      growth in Neuroblastoma and Pediatric Sarcomas In vitro and In vivo.
AB  - The IL-6/JAK/STAT pathway is a key signal transduction pathway implicated in the
      pathogenesis of many human cancers, suggesting that kinase inhibitors targeting
      JAK/STAT3 may have a broad spectrum of antitumor activity. AZD1480, a
      pharmacological JAK1/2 inhibitor, exhibits anti-tumor potency in multiple adult
      malignancies. To evaluate the efficacy of inhibition of JAK/STAT3 signal
      transduction pathway we assessed the activity of AZD1480 in pediatric
      malignancies using preclinical models of three highly malignant pediatric solid
      tumors: neuroblastoma (NB), rhabdomyosarcoma (RMS) and the Ewing Sarcoma Family
      Tumors (ESFT). In this study, we employed panels of biomedical and biological
      experiments to evaluate the in vitro and in vivo activity of AZD1480 in NB, RMS
      and ESFT. Our data indicate that AZD1480 blocks endogenous as well as IL-6
      induced STAT3 activation. AZD1480 decreases cell viability in 7/7NB, 7/7RMS and
      2/2 ESFT cell lines (median EC50 is 1.5 MUM, ranging from 0.36-5.37 MUM). AZD1480
      induces cell growth inhibition and caspase-dependent apoptosis in vitro and
      decreases expression of STAT3 target genes, including cell cycle regulators
      CyclinD1, 3 and CDC25A, anti-apoptotic genes Bcl-2 and survivin, the metastasis
      related factor TIMP-1 and c-Myc. In vivo studies showed AZD1480 significantly
      decreased tumor growth and prolonged overall survival in tumor-bearing mice.
      Tumors from AZD1480-treated mice showed inhibition of activated STAT3 as well as
      decreased expression of STAT3 downstream targets. Our study provides strong
      evidence of the anti-tumor growth potency of JAK inhibitor AZD1480 in pediatric
      solid tumors, providing proof-of principle that inhibition of the JAK/STAT3
      signal transduction could be a promising therapeutic target for high-risk
      pediatric solid tumors.

PMID- 23531922
TI  - A two year longitudinal outcome study of addicted health care professionals: an
      investigation of the role of personality variables.
AB  - The co-morbidity of personality disorders (PDs) and other dysregulatory
      personality patterns with addiction have been well-established, although few
      studies have examined this interplay on long-term sobriety outcome. In addition,
      health care professionals suffering from addiction have both a significant public
      health impact and a unique set of treatment and recovery challenges. The aim of
      this study was to investigate if personality variables differentiated sobriety
      outcome in this population over a two year interval. A clinical sample of health
      care professionals participated in a substance abuse hospital treatment program
      individually tailored with respect to personality. Participants took the
      Temperament and Character Inventory and the Millon Clinical Multiaxial Inventory
      at intake, and were tracked two years post-discharge to determine sobriety
      status. Univariate analyses showed antisocial personality, female gender, and
      alcohol dependence were independent predictors of relapse, however a significant
      relationship between personality and substance use did not exist in multivariate
      analysis when controlling for demographic variables The lack of multivariate
      relationships demonstrates the heterogeneity in self-report measures of
      personality, which suggests the interplay of personality and addiction is complex
      and individualized.

PMID- 23531923
TI  - Niche partitioning between close relatives suggests trade-offs between adaptation
      to local environments and competition.
AB  - Niche partitioning among close relatives may reflect trade-offs underlying
      species divergence and coexistence (e.g., between stress tolerance and
      competitive ability). We quantified the effects of habitat and congeneric species
      interactions on fitness for two closely related herbaceous plant species, Mimulus
      guttatus and Mimulus laciniatus, in three common habitat types within their
      sympatric range. Drought stress strongly reduced survival of M. guttatus in fast
      drying seeps occupied by M. laciniatus, suggesting that divergent habitat
      adaptation maintains this niche boundary. However, neither seedling performance
      nor congeneric competition explained the absence of M. laciniatus from shady
      streams where M. guttatus thrives. M. laciniatus may be excluded from this
      habitat by competition with other species in the community or mature M. guttatus.
      Species performance and competitive ability were similar in sympatric meadows
      where plant community stature and the growing season length are intermediate
      between seeps and streams. Stochastic effects (e.g., dispersal among habitats or
      temporal variation) may contribute to coexistence in this habitat. Habitat
      adaptation, species interactions, and stochastic mechanisms influence sympatric
      distributions for these recently diverged species.

PMID- 23531924
TI  - Built environment and change in body mass index in older women.
AB  - We examined the association between neighborhood walkability and changes in body
      mass index (BMI) and obesity during a 14-year follow-up among community-dwelling
      women 71 years of age on average (n=1008 representing 253 census tracts).
      Multilevel models predicted change in BMI or incidence of obesity controlling for
      age, marital status, number of incident comorbidities, self rated health, and
      death, over a follow-up of 14 years. Among non-sedentary older women, average BMI
      remained stable (beta=0.007, p=0.291); risk of becoming obese increased 3% per
      year (odds ratio=1.03, 95% CI 1.01, 1.05). Walkability was not associated with
      BMI or risk of obesity. Future research should consider additional neighborhood
      characteristics relevant to older adults, such as proximity to retail, public
      transit, or parks.

PMID- 23531925
TI  - Melting down the Ice Queen: an integrative treatment of anorexia nervosa.
AB  - A 23-year-old woman with anorexia nervosa (AN) and a strong need for control was
      offered an integrative treatment, empowering the patient to be an active
      participant and advocating shared decision-making. To emphasise this, both the
      therapist and patient describe their views on the therapy. The integrative
      treatment resulted in more psychological flexibility and behavioural
      improvements, as is evident from an increased weight, a decreased dietary
      restriction and an increased valued action. The strength of this integrative
      treatment is based on accepting and encouraging patient's self-chosen treatment
      method, within healthy limits, and thereby creating a flexible, supportive and
      empowering therapeutic alliance. More research is needed to test the efficacy of
      combining complementary therapies within conventional treatments of AN.

PMID- 23531926
TI  - Ruptured sinus of Valsalva aneurysm from left coronary sinus into right atrium: a
      rare anomaly with an odd presentation.
AB  - We report a case of a 42-year-old man presenting with shortness of breath and
      palpitation on exertion, who was evaluated to have left sinus of Valsalva
      aneurysm rupturing into right atrium. This is a very rare congenital cardiac
      anomaly with variable clinical presentation ranging from asymptomatic detection
      on imaging to acute coronary syndrome and sudden cardiac death. Rupture is the
      most dreaded complication and usually manifests as an acute event. Aneurysmal
      dilation less commonly affects the left sinus and rupture into the right atrium
      is still rarer and a chronic insidious presentation as in this case is odd.

PMID- 23531927
TI  - An 8-year follow-up of a patient with acute myocardial infarction complicated
      with ventricular rupture and cerebral thrombosis treated conservatively: a cohort
      study.
AB  - Cardiac rupture is a complication of myocardial infarction (MI) with extremely
      high mortality. Poor prognosis is usually predicted in conservatively treated
      patients. The treatment for cardiac rupture and thrombosis is in conflict. We
      reported an MI case of cardiac rupture and cerebral thrombosis using a
      conservative method. This case indicated that (1) It is noteworthy that patients
      suffering from the subacute form of rupture may remain haemodynamically stable.
      This type of patients may benefit from a conservative treatment without
      anticoagulation or antiplatelet at the onset of cardiac rupture. (2) Thirty days
      following cardiac rupture, it is safe to use warfarin anticoagulation for
      cerebral thrombosis treatment. The patient suffered from acute MI, cardiac
      rupture and subsequently cerebral thrombosis. We treated this patient in a
      conservative manner and the patient remained alive for 8 years. This case
      suggested that it may be safe to use warfarin anticoagulation treatment for
      cerebral thrombosis 30 days following cardiac rupture.

PMID- 23531928
TI  - Hurler syndrome (Mucopolysaccharidosis type I).

PMID- 23531929
TI  - Treatment of mobile right heart thrombi with low-molecular-weight heparin.
AB  - Treatment of choice in patients with mobile thrombi in the right heart chambers
      is still controversial owing to the increased risk of recurrent pulmonary
      embolism (PE). Thrombolysis and surgical or catheter embolectomy are the
      preferred options. We present a case of an elderly patient with PE and free
      floating atrial thrombi who was treated successfully with low-molecular-weight
      heparin (LMWH).

PMID- 23531931
TI  - Intraoral teratoma in a newborn presenting as severe respiratory distress.
AB  - A new born female presented to us immediately after birth with mass protruding
      from the mouth, with severe respiratory distress and was immediately intubated.
      Antenatal ultrasonography did not reveal any abnormality. On examination, a non
      pulsatile, multilobulated, 4 cm*5 cm sized mass of variable consistency was seen
      originating from the palate with no other associated congenital anomaly. CT
      showed a large heterogeneous mass arising from the hard palate with few
      hyperdense calcific areas with no intracranial extension. Mass was excised
      completely. Histopathological examination showed features of mature teratoma.

PMID- 23531930
TI  - Small colony variant-producing S aureus prosthesis joint infection highlighted by
      sonication and treated with prolonged high doses of daptomycin.

PMID- 23531932
TI  - Leiomyoma of the bladder.

PMID- 23531933
TI  - Tuberculosis: still an enigma. Presenting as mycotic aneurysm of aorta.

PMID- 23531934
TI  - A rare cause of superior vena cava syndrome.

PMID- 23531935
TI  - Reversible dementia and gait disturbance as a result of polypharmacy.

PMID- 23531936
TI  - Giant iris cyst in an 11-year-old child.

PMID- 23531937
TI  - Incidental pathologically proven pulmonary hamartoma in a patient with carcinoma
      tongue.
AB  - Pulmonary hamartomas are usually clinically silent and found incidentally on
      chest radiographs. They can lead to diagnostic confusion especially in patients
      who have been previously treated for primary cancers at other sites. This can
      lead to consideration of metastatic malignancy as the primary diagnostic
      possibility. In this case, evaluation of a solitary pulmonary nodule (SPN) in a
      patient with carcinoma of tongue led to the diagnosis of pulmonary chondroid
      hamartoma. This highlights the fact that a pulmonary nodule in a patient with
      progressive cancer at another site does not always indicate pulmonary metastasis.

PMID- 23531938
TI  - Primary synovial osteochondromatosis of the ankle.

PMID- 23531939
TI  - Prostate abscess: MRSA spreading its influence into Gram-negative territory: case
      report and literature review.
AB  - Prostate abscess is a rare complication of an ascending urinary tract infection
      (UTI). Its incidence has reduced secondary to routine and early use of
      antibiotics for treatment of UTIs. Prostate abscess has been reported in patients
      with uncontrolled diabetes, prolonged indwelling urinary catheters, prostate
      biopsy or other instrumentation of lower urinary tract. Prostate abscess is most
      commonly associated with Gram-negative bacteria. Staphylococcus aureus is rarely
      implicated and has been reported in patients with underlying risk factors like
      long-term or uncontrolled diabetes, intravenous drug abuse or bacteraemia. We
      present a rare case of prostate abscess due to methicillin resistant S aureus
      without obvious risk factors.

PMID- 23531940
TI  - Mount Fuji sign following subdural haematoma evacuation.

PMID- 23531941
TI  - Simple pyridyl-salicylimine-based fluorescence "turn-on" sensors for distinct
      detections of Zn2+, Al3+ and OH- ions in mixed aqueous media.
AB  - Simple pyridyl-salicylimine derivatives (F1, F2 and F3) are reported for the
      first time as fluorescence "turn-on" sensors for distinct detections of Zn(2+),
      Al(3+) and OH(-) ions in mixed-aqueous media CH3CN/H2O with volume ratios of 6/4
      and 3/7 (at pH = 7 and 25  degrees C) via internal charge transfer (ICT),
      chelation enhanced fluorescence (CHEF), and deprotonation mechanisms. F1 and F2
      show diverse turn-on sensing applications to Zn(2+), Al(3+) and OH(-) ions, but
      F3 exhibited the fluorescence turn-on sensing to Al(3+) and OH(-) ions in
      CH3CN/H2O (6/4; vol/vol). F1+Zn(2+) and F2+Zn(2+) complexes revealed the
      reversibilities and ratiometric displacements of Zn(2+) with ethylene diamine
      tetra acetic acid (EDTA) and Al(3+) ions, respectively, in CH3CN/H2O (6/4;
      vol/vol). On the other hand, F1, F2 and F3 in CH3CN/H2O (3/7; vol/vol) showed
      sensitivities only to Al(3+) ions but negligible selectivities to OH(-) ions.
      Stoichiometry of all sensor complexes were calculated as 1 : 1 by job's plots
      based on UV/Vis and PL titrations. The complex formation and binding sites of all
      sensor materials were well characterized by (1)H, (13)C NMR, and mass (FAB)
      spectral analysis. Detection limits were calculated from standard deviations and
      linear fitting calculations. The association constant (log K(a)) values of sensor
      complexes were evaluated from the fluorescence binding isotherms. The
      fluorescence decay constant (tau) values were estimated from time resolved
      fluorescence studies. Time, temperature, pH and solvent concentration effects
      towards sensor responses were fully investigated in this report.

PMID- 23531942
TI  - [Horse research network conference].

PMID- 23531943
TI  - [Dog population and dog breeds in Switzerland from 1955 to 2008].
AB  - Aim of this study is to present a survey of the dog population and breed
      distribution in Switzerland from 1955 to 2008 as basis to realize a population
      based canine cancer register for Switzerland. The number of dogs rose from
      309'000 in 1955 to approximately 500'000 in 2008 correlating with a parallel
      increase of human population. The ratio of dogs per 100 inhabitants remains
      stable. This ratio is lower in German speaking compared to French or Italian
      speaking Cantons. The variety and popularity of breeds changed from 1955 to 2008,
      "winners" are Labrador and Golden Retrievers, Yorkshire and Jack Russel Terriers.
      Less popular breeds over the years are German Sheherd dogs and Poodles.

PMID- 23531944
TI  - [Clinical evaluation of the new coat colour macchiato in a male Franches
      Montagnes horse].
AB  - In April 2008 a Franches-Montagnes colt was born with an unusual coat colour
      phenotype which had never been observed in that population before. The foal
      showed extended white markings on body and legs, a white head and blue eyes. As
      both parents have an unremarkable bay coat colour phenotype, a de novo mutation
      was expected in the offspring and a candidate gene approach revealed a
      spontaneous mutation in the microphthalmia associated transcription factor gene
      (MITF). A detailed clinical examination in 2010 indicated an impaired hearing
      capacity. As in the American Paint Horse large white facial markings in
      combination with blue eyes are associated with deafness, the hearing capacity of
      the stallion was closer examined performing brainstem auditory-evoked responses
      (BAER). The BAER confirmed bilateral deafness in the Franches-Montagnes colt. It
      is assumed that the deafness is caused by a melanocyte deficiency caused by the
      MITF gene mutation. Unfortunately, due to castration of the horse, the causal
      association between the mutation in the MITF gene and clinical findings cannot be
      confirmed by experimental matings.

PMID- 23531949
TI  - [Necessary time off for looking after sick family members].

PMID- 23531950
TI  - Alveolar soft-part sarcoma of the orbit: report of 2 cases with review of the
      literature.
AB  - Alveolar soft-part sarcoma (ASPS) is a translocation-associated sarcoma that
      occurs most commonly in the lower extremities and rarely in orbit. Only 34
      orbital cases have been reported in the literature, and it is often misdiagnosed
      due to its rare occurrence and nonspecific clinical findings. The optimal
      treatment remains controversial, although in general, aggressive surgical
      resection is advocated. Here, the authors present 2 cases of orbital ASPS and a
      review of the literature. 

PMID- 23531951
TI  - Orbital B-lymphocyte depletion in a treatment failure of rituximab for thyroid
      eye disease.
AB  - Rituximab is an emerging treatment for thyroid eye disease. Rituximab effectively
      depletes circulating CD20+ B-lymphocytes; however, its effect on target tissues
      has not been well-studied. Failures of rituximab have been infrequently reported.
      The authors describe a patient treated with rituximab for thyroid eye disease who
      failed to respond to treatment, and underwent orbital decompression. Orbital fat
      samples and peripheral blood samples were evaluated for the presence of CD20+ B
      lymphocytes. Complete depletion of CD20+ B-lymphocytes was demonstrated in both
      the orbit and the blood. This case demonstrates that rituximab effectively
      depletes orbital CD20+ B-lymphocytes, and this depletion was maintained for 2
      months despite a clinical deterioration. 

PMID- 23531953
TI  - The magic of the Southern Society for Clinical Investigation: can we make the
      vanishing physician-scientist reappear?

PMID- 23531952
TI  - Lateral rectus myositis mimicking an abducens nerve palsy in a pregnant woman.
AB  - Myositis is a rare unknown inflammatory disorder of the skeletal muscle tissue.
      Generalized inflammatory myopathies, polymyositis, and dermatomyositis have been
      reported during pregnancy. Isolated orbital myositis in pregnancy has not been
      previously described in the literature. The authors report a case of left
      isolated orbital myositis in a primigravida at 38 weeks gestation affecting the
      patient's left lateral rectus muscle. MRI of the orbit was consistent with the
      diagnosis. She showed remarkable clinical improvement with oral corticosteroids
      therapy. 

PMID- 23531954
TI  - The diabetes initiative of South Carolina and the 18th Annual Diabetes Fall
      Symposium for Health Care Professionals.
AB  - The Diabetes Initiative of South Carolina (DSC) is charged with the development
      of guidelines for the management of diabetes and supporting adherence to evidence
      based standards for education and care. The DSC is committed to lowering the
      burden of diabetes in the state through translation of evidence-based standards
      of clinical practice, and patient and community education centered on blood
      glucose control, blood pressure control, healthy eating, physical activity, and
      foot care. The DSC has developed many programs for the education of a variety of
      health professionals about diabetes and its complications. DSC has sponsored 18
      Annual Diabetes Fall Symposia for primary health care professionals featuring
      education on all aspects of diabetes mellitus. The intent of the program is to
      enhance the lifelong learning process of physicians, nurses, pharmacists,
      dietitians and other health care professionals by providing educational
      opportunities and to advance the quality and safety of patient care.

PMID- 23531955
TI  - Diabetes and driving safety: science, ethics, legality and practice.
AB  - Diabetes affects over 25 million people in the United States, most of whom are
      over the age of 16 and many of whom are licensed to drive a motor vehicle. Safe
      operation of a motor vehicle requires complex interactions of cognitive and motor
      functions and medical conditions that affect these functions often will increase
      the risk of motor vehicle accidents (MVA). In the case of diabetes, hypoglycemia
      is the most common factor that has been shown to increase MVA rates. When people
      with diabetes are compared with nondiabetic controls, systematic analyses show
      that the relative risk of MVA is increased by between 12% and 19% (Relative Risk
      Ratio 1.12-1.19). In comparison, the RRR for attention deficit hyperactivity
      disorder is 4.4 and for sleep apnea is 2.4. Epidemiologic research suggests that
      patients at risk for hypoglycemia-related MVAs may have some characteristics in
      common, including a history of severe hypoglycemia or of hypoglycemia-related
      driving mishaps. Experimental studies also have shown that people with a history
      of hypoglycemia-related driving mishaps have abnormal counter-regulatory
      responses to hypoglycemia and greater cognitive impairments during moderate
      hypoglycemia.

PMID- 23531956
TI  - Ocular disease, knowledge and technology applications in patients with diabetes.
AB  - An estimated 25.8 million children and adults in the United States, approximately
      8.3% of the population, have diabetes. Diabetes prevalence varies by race and
      ethnicity. African Americans have the highest prevalence (12.6%), followed
      closely by Hispanics (11.8%), Asian Americans (8.4%) and whites (7.1%). The
      purpose of this article was to discuss the ocular complications of diabetes, the
      cultural and racial differences in diabetes knowledge and the role of
      telemedicine as a means to reach the undeserved who are at risk of complications.
      Information on the pathophysiology of ocular disease in patients with diabetes
      and the role of telemedicine in diabetes care was derived from a literature
      review. National Institutes of Health online resources were queried to present
      data on the racial and cultural understandings of diabetes and diabetes-related
      complications. The microvascular ocular complications of diabetes are discussed
      for retinopathy, cataracts, glaucoma and ocular surface disease. Racial and
      cultural differences in knowledge of recommended self-care practices are
      presented. These differences, in part, may explain health disparities and the
      increased risk of diabetes and its complications in rural minority communities.
      Finally, advances in telemedicine technology are discussed that show improvements
      in metabolic control and cardiovascular risk in adults with type 2 diabetes.
      Improving provider and patient understanding of diabetes complications may
      improve management and self-care practices that are important for diabetes
      control. Telemedicine may improve access to diabetes specialists and may improve
      self-management education and diabetes control particularly in rural and
      underserved communities.

PMID- 23531958
TI  - Glucocorticoid-induced hyperglycemia.
AB  - OBJECTIVES: Provide treatment guidelines for glucocorticoid-induced hyperglycemia
      and to understand the clinical implications of glucocorticoid-induced
      hyperglycemia. METHODS: The authors analyzed an electronic search (Medline) and a
      literature review of the pertinent articles published from 1980 to September
      2012. RESULTS: In patients treated with glucocorticoids, the odds ratio for
      development of new-onset diabetes mellitus has been reported to be 1.36 to 2.31.
      The prevalence of abnormal glucose metabolism in post renal transplant patients
      taking glucocorticoids has been reported to be 17% to 32%. Sustained
      glucocorticoid treatment increases the potential for future cardiovascular
      disease through multiple pathways, resulting in a trade-off between benefit and
      harm. Complications related to glucocorticoid treatments are associated with the
      total glucocorticoid dose and duration of therapy. Other risk factors include age
      and body mass index. Understanding the pharmacodynamics and clinical implications
      of glucocorticoid-induced hyperglycemia can promote recognition and improvement
      of its treatment. CONCLUSIONS: Glucocorticoid-induced hyperglycemia has
      significant clinical implications in patients with diabetes mellitus and without
      diabetes mellitus. Early recognition and proper proactive management of
      glucocorticoid-induced hyperglycemia should enhance care for patients receiving
      glucocorticoid treatment. Furthermore, treatment has been effective for both the
      inpatient and the outpatient settings.

PMID- 23531957
TI  - Oral health and type 2 diabetes.
AB  - Type 2 diabetes mellitus has been described as a new epidemic. Approximately 285
      million people worldwide suffer from diabetes, and this number is predicted to
      increase by approximately 50% by year 2030. This article will review oral health
      manifestations of diabetes and discuss associations between periodontal disease
      and diabetes. Although there is a strong body of evidence that supports the
      relationship between oral health and type 2 diabetes mellitus, oral health
      awareness is lacking among patients with diabetes and other health professionals.
      There is a need for the treating physician to be educated about the various oral
      manifestations of diabetes so that they can be diagnosed early and timely
      referrals to oral health specialists can be made. The established link between
      periodontitis and diabetes calls for an increased need to study ways to control
      both diseases, particularly among populations with health disparities and limited
      access to oral and health care.

PMID- 23531959
TI  - All grown up: moving from pediatric to adult diabetes care.
AB  - Transition of care from a child-centered care environment to an adult-centered
      care environment for pediatric patients with diabetes is needed to ensure
      continued diabetes care. The transition process should start early and be
      tailored to the developmental stage of the patient. The typical challenges of
      adolescence and young adulthood including pubertal changes, parent-child conflict
      and the potential for high-risk behavior complicate the transition process.
      Methods of transfer of care are variable and less than optimal. Ongoing study and
      continued efforts are needed to improve the transition process so that young
      patients with diabetes receive high quality uninterrupted care.

PMID- 23531960
TI  - Pharmacotherapy of obesity: clinical treatments and considerations.
AB  - Obesity is a world-wide epidemic associated with significant morbidity and
      mortality which costs billions of dollars per year. The associated related
      conditions are many and include heart disease, stroke, type II diabetes mellitus,
      sleep apnea and certain types of cancer. Given that it is a multifactorial
      problem, the treatments must also address the numerous causes associated with the
      development of obesity. The neurohormonal regulation of feeding and energy is a
      complex system often necessitating modification through more than 1 pathway to
      achieve weight loss. Therefore, in addition to lifestyle changes, attenuation of
      caloric intake and increase in caloric expenditure, pharmacotherapies, including
      combination medications, may prove beneficial in its treatment. Adding to the
      current available pharmacotherapies for obesity, the Food and Drug Administration
      has recently approved 2 new combination medications known as lorcaserin (Belviq)
      and phentermine-topiramate (Qsymia). As with these and other medications used for
      weight loss, clinical cautions, side effects, precise review of patients' medical
      history and selecting the appropriate medication are imperative. Additionally,
      close follow-up is necessary in patients undergoing treatment for weight loss. As
      weight loss progresses, patients who are currently undergoing concomitant
      treatment for comorbid diabetes and hypertension need to be monitored for
      appropriate changes in medications used to treat those conditions. Weight loss is
      often accompanied by improvement in blood pressure and glucose levels and
      therefore resting blood pressure and fasting and/or postprandial plasma glucose
      levels should be monitored at follow-up. Although unique to each individual, the
      benefits of weight loss are substantial and can improve well-being and physical
      health.

PMID- 23531961
TI  - Improving diabetes management with mobile health technology.
AB  - Diabetes affects 25.8 million persons in the United States, and these persons
      make more than 35 million ambulatory care visits annually. Yet, less than half of
      persons with diabetes meet the recommended levels of A1C, blood pressure and
      lipid control. One innovative approach is to use mobile health technologies to
      help patients better manage their diabetes and related conditions, and 85% to 90%
      of patients have access to mobile health technology. A brief review of the
      guidelines for diabetes care and mobile health technology that can support the
      guidelines are reported related to (1) glycemic control and self-monitoring of
      blood glucose, (2) pharmacological approaches and medication management, (3)
      medical nutrition therapy, (4) physical activity and resistance training, (5)
      weight loss, (6) diabetes self-management education and (7) blood pressure
      control and hypertension. The patient and provider are encouraged to explore
      possibilities for mobile health technologies that can support behavior change.

PMID- 23531962
TI  - South Carolina guidelines for diabetes care 2013.
AB  - BACKGROUND: There is a huge economic burden of diabetes in South Carolina.
      METHODS: The South Carolina Guidelines for Diabetes Care were based on the 2013
      Standards of Medical Care from the American Diabetes Association. RESULTS: From a
      review of the Diabetes Quality Indicators in South Carolina 2007, Medicare claims
      data show: 65% of South Carolinians with diabetes insured by Medicare received 2
      A1C test per year, 54% received an eye examination and 78% received a lipid
      panel. Only 42% of these individuals with diabetes had all 3 tests in the same
      year. In addition, only 50% of individuals with diabetes in South Carolina
      attended a diabetes self-management class. To improve the statistics and
      outcomes, the Diabetes Advisory Council provided the evidence-based South
      Carolina Guidelines for Diabetes Care. They are based on the 2013 Standards of
      Medical Care from the American Diabetes Association. These guidelines have been
      promoted at the continuing education programs sponsored by the Diabetes
      Initiative of South Carolina and the South Carolina Division of Diabetes
      Prevention and Control and distributed in the community sites by the Racial and
      Ethnic Approaches to Community Health coalition. CONCLUSIONS: The South Carolina
      Guidelines for Diabetes will provide evidence-based therapy and monitoring to
      minimize complications from diabetes and promote a higher quality of life for
      those with diabetes.

PMID- 23531963
TI  - Brief update on the burden of diabetes in South Carolina.
AB  - Diabetes is a serious disease, which is often accompanied by complications, such
      as blindness, kidney failure, heart attacks, strokes and amputations. High blood
      pressure and abnormal cholesterol levels are frequent comorbidities. Diabetes has
      an immense impact on public health and medical care. In South Carolina (SC),
      medical costs rise with increased duration of the disease, and lifespan is
      shortened by 5 to 10 years in most patients. To describe the burden of diabetes
      in SC, we examined the public health surveillance systems available to estimate
      the prevalence, mortality and hospitalization rates and some disability
      statistics and hospital charges. Diabetes is the 7 leading cause of death in SC,
      directly or indirectly claiming more than 3,000 lives annually, and the 5 leading
      cause of death in blacks, claiming about 1,200 black lives each year. Minorities,
      predominantly blacks, experienced a substantially higher death rate and more
      years of potential life lost than whites. The racial disparity in mortality has
      widened over the past 10 years. People with diabetes are at increased risk for
      blindness, lower extremity amputation, kidney failure, nerve disease,
      hypertension, ischemic heart disease and stroke. Approximately 450,000 South
      Carolinians are affected by diabetes, many of whom were still undiagnosed in
      2010. One of every 5 patients in a SC hospital has diabetes, and 1 in every 10
      visits to a SC emergency room is diabetes related. The total charges for diabetes
      and diabetes-related hospitalizations and emergency room visits were more than
      $4.2 billion in 2010.

PMID- 23531964
TI  - The evolving role of the diabetes educator.
AB  - The roles of the diabetes educator (DE) have expanded significantly from the
      basic instruction on self-care on which the profession was established and now
      encompass a range of key responsibilities within diabetes care. A major focus of
      recent literature has been evaluation of the effectiveness of diabetes self
      management education for such factors as reducing the incidence of diabetes,
      improving clinical parameters and improving medication adherence. This review
      describes how DEs and diabetes educational services have impacted patient health,
      how the role of the DE has changed in the past decade and what roles these
      professionals may serve in the evolving paradigm of primary care for patients
      with diabetes. Looking forward, the integration of DEs into coordinated care
      teams will likely increase to meet the challenges associated with providing
      quality care to a rapidly expanding population with type 2 diabetes.

PMID- 23531965
TI  - Impact of diabetes mellitus on treatment outcomes of tuberculosis patients in
      tertiary care setup.
AB  - BACKGROUND: Concurrent diabetes mellitus (DM) with tuberculosis (TB) has an
      increased risk of treatment failure. This study was aimed to evaluate treatment
      outcomes in patients with TB with and without DM. METHODS: A retrospective cohort
      study was conducted at respiratory clinic of Hospital Pulau Pinang, Malaysia. All
      TB-registered patients from January 2006 to December 2007 were included in the
      study. A validated data collection form was used for collecting data. World
      Health Organization's criterion was used for categorizing treatment outcomes.
      Data were analyzed by using SPSS 16. RESULTS: Of 1267 patients, 338 patients
      (26.7%) had concurrent TB-DM. In multivariate analysis, TB-DM was more likely to
      be present in Chinese (odds ratio [OR] = 1.401, P = 0.011), patients having age
      of 46 to 60 years (OR = 3.168, P < 0.001) and >60 years (OR = 2.524, P < 0.001)
      and patients with pulmonary TB (OR = 2.079, P < 0.001). Nine hundred and eighty
      five (78.8%) patients were successfully treated. No statistically significant
      difference was observed between 2 groups: patients with TB-DM and patients with
      only TB. Successful treatment outcomes were observed in patients having age of 46
      to 60 (OR = 1.567, P = 0.001), whereas male gender (OR = 0.721, P = 0.049) and
      patients with relapse TB (OR = 0.494, P = 0.002) were less likely to have
      successful treatment outcome. CONCLUSIONS: High prevalence of TB-DM in the study
      signifies the fact that patients with DM are at high risk of developing TB.
      Treatment outcomes in both groups were comparable. The gender-based and age-based
      disparity in TB treatment outcomes in this study indicates the importance of
      gender-specific and age-specific strategies of TB management.

PMID- 23531966
TI  - Dental clinics as potent sources for screening undiagnosed diabetes and
      prediabetes.
AB  - INTRODUCTION: This pilot study investigated the efficacy of dental clinics as
      potent sources for screening diabetes and prediabetes in undiagnosed individuals.
      METHODS: Data were randomly collected from 385 patients (aged 40 years and older)
      visiting dental clinics. Patients already having a diagnosis of diabetes and/or
      prediabetes were excluded. Demographic data, body mass index and family and
      dental histories were recorded. Signs and symptoms of diabetes were investigated.
      Random blood glucose levels (RBGLs) were recorded. Individuals with RBGL >=110
      mg/dL underwent the oral glucose tolerance test and the glycosylated hemoglobin
      test (HbA1c). RESULTS: Of the 385 patients, 60% (232) had RBGL <110 mg/dL,
      whereas 40% (153) had RBGL >=110 mg/dL. Prevalence of confirmed diabetes and
      prediabetes among the study participants was 16.4% and 15.8%, respectively. Body
      mass index was significantly higher among patients with diabetes and prediabetes
      as compared with healthy controls. HbA1c level was statistically significantly
      higher among patients with diabetes than among patients with prediabetes.
      Symptoms of polyuria and polydipsia were significantly higher among patients with
      diabetes than in those without diabetes. CONCLUSIONS: A high percentage of
      undiagnosed type 2 diabetes and prediabetes among patients visiting dental
      clinics was found compared with that reported in the medical literature. Further
      studies with a lager sample size are needed to confirm these results.

PMID- 23531968
TI  - Ischemic colitis in athletes.

PMID- 23531970
TI  - "What do you mean, a wheelchair athlete?".

PMID- 23531971
TI  - Foot injuries in runners.
AB  - Injuries of the foot are common among both elite and recreational runners.
      Overuse accounts for most of these injuries. Plantar fasciitis and tendinopathies
      of the midfoot and forefoot have a high incidence in running athletes. These
      injuries may present with significant pain but often resolve with rest and
      rehabilitation. Bone injuries caused by overuse also have a high prevalence among
      runners. The metatarsals, tarsal navicular, and sesamoids are most at risk for
      stress damage. Most running injuries are self-limited and pose little detriment
      if diagnosis is delayed. Navicular and sesamoid stress fractures may impart
      significant long-term consequences, and thus, a clinical suspicion of either
      fracture warrants definitive diagnosis and treatment. Barefoot running recently
      has garnered increased attention, but currently, there is a lack of prospective
      studies regarding its injury reduction.

PMID- 23531972
TI  - Treatment options for patellar tendinopathy: critical review.
AB  - Patellar tendinopathy is a painful knee injury due to overuse common among
      jumping athletes. Because rest from sport is neither a feasible nor an effective
      treatment for patellar tendinopathy in elite athletes, active treatment options
      are needed. Treatment may be conservative, injection-based, or surgical. This
      review synthesizes findings from 32 studies of varying quality published between
      2001 and 2011. Painful eccentric squats using a 25 degrees -decline board is
      supported as a first-line treatment. Extracorporeal shock wave therapy is no more
      effective than placebo. Sclerosing injections seem to be effective, but the
      evidence is not definitive. Shaving of abnormal tissue via arthroscopic surgery
      with real-time ultrasound guidance is superior to sclerosing injections. Steroid
      injections are inferior to exercise interventions and are not recommended.
      Injections of autologous blood, platelet-rich plasma, and hyperosmolar dextrose
      are unproven and experimental. Clinicians need to have a comprehensive knowledge
      of the evidence in the literature, as well as training and experience, when
      treating patellar tendinopathy.

PMID- 23531973
TI  - Diagnosis and management of ulnar collateral ligament injuries in throwers.
AB  - Although ulnar collateral ligament (UCL) injuries are reported most commonly in
      baseball players (especially in pitchers), these also have been observed in other
      throwing sports including water polo, javelin throw, tennis, and volleyball. This
      article reviews the functional anatomy and biomechanics of the UCL with
      associated pathophysiology of UCL injuries of the elbow of the athlete
      participating in overhead throwing. Evaluation, including pertinent principles in
      history, physical examination, and imaging modalities, is discussed, along with
      the management options.

PMID- 23531974
TI  - Use of viscosupplementation for knee osteoarthritis: an update.
AB  - Because of the rising numbers of patients affected by osteoarthritis (OA),
      management decisions on how to minimize pain and improve function in OA patients
      are important. Intra-articular hyaluronic acid (IAHA) knee injections have become
      a common treatment in the management of knee OA. In an editorial appearing in the
      2007 National Knowledge Week on Osteoarthritis: National Health Service Evidence,
      four questions were asked about the clinical use of IAHA treatment for OA: 1) Who
      is the ideal candidate for HA viscosupplementation? 2) Do the mechanical and
      biological effects differ in importance in different stages of the disease? 3)
      What is the ideal dose in early- and late-stage OA? 4) Can the biological effect
      be delivered by means other than injection? These key issues are addressed. On
      the basis of results from several systemic reviews and meta-analyses, we conclude
      that IAHA knee injections in patients with knee OA result in modest improvements
      when measured by validated outcomes.

PMID- 23531975
TI  - Weightlifter with elbow pain.

PMID- 23531976
TI  - Current review of injuries sustained in mixed martial arts competition.
AB  - Mixed martial arts (MMA) have enjoyed a tremendous growth in popularity over the
      past 10 years, yet there remains a paucity of information with respect to common
      injuries sustained in MMA competitions. In the available studies, certain trends
      pertaining to risk factors for injury, as well as the most common injuries
      sustained in MMA competition, were noted. Common risk factors include being the
      losing fighter, history of knockout or technical knockout, and longer fight
      duration. Common injuries that were noted include lacerations and abrasions,
      followed by injuries to the face and ocular region. Concussions with or without
      loss of consciousness also were noted in MMA competition.

PMID- 23531977
TI  - Football injuries: current concepts.
AB  - Football is one of the most popular sports in the United States and is the
      leading cause of sports-related injury. A large focus in recent years has been on
      concussions, sudden cardiac death, and heat illness, all thought to be largely
      preventable health issues in the young athlete. Injury prevention through better
      understanding of injury mechanisms, education, proper equipment, and practice
      techniques and preseason screening may aid in reducing the number of injuries.
      Proper management of on-field injuries and health emergencies can reduce the
      morbidity associated with these injuries and may lead to faster return to play
      and reduced risk of future injury. This article reviews current concepts
      surrounding frequently seen football-related injuries.

PMID- 23531978
TI  - Running injuries - changing trends and demographics.
AB  - Running injuries are common. Recently the demographic has changed, in that most
      runners in road races are older and injuries now include those more common in
      master runners. In particular, Achilles/calf injuries, iliotibial band injury,
      meniscus injury, and muscle injuries to the hamstrings and quadriceps represent
      higher percentages of the overall injury mix in recent epidemiologic studies
      compared with earlier ones. Evidence suggests that running mileage and previous
      injury are important predictors of running injury. Evidence-based research now
      helps guide the treatment of iliotibial band, patellofemoral syndrome, and
      Achilles tendinopathy. The use of topical nitroglycerin in tendinopathy and
      orthotics for the treatment of patellofemoral syndrome has moderate to strong
      evidence. Thus, more current knowledge about the changing demographics of runners
      and the application of research to guide treatment and, eventually, prevent
      running injury offers hope that clinicians can help reduce the high morbidity
      associated with long-distance running.

PMID- 23531979
TI  - Update on artistic gymnastics.
AB  - Gymnastics continues to be one of the most popular and injury-prone sports in the
      United States. The National Collegiate Athletic Association cites women's
      artistic gymnastics as second only to spring football in its rate of injury
      during practices, and fourth overall when combining competition and practice
      injury rates. Because of the physical demands of the sport of gymnastics, a wide
      variety of injuries occur. This article reviews some of the most recent
      literature on the sport of artistic gymnastics. A broad differential may be
      required to diagnose correctly a presenting injury in a gymnast.

PMID- 23531980
TI  - Type I collagen and polyvinyl alcohol blend fiber scaffold for anterior cruciate
      ligament reconstruction.
AB  - The aim of this study was to perform an evaluation of a braided fiber scaffold
      for anterior cruciate ligament (ACL) reconstruction. The scaffold was composed of
      50% type I collagen (Col-I) and 50% polyvinyl alcohol (PVA). First, the
      biocompatibility and in vitro weight loss of the scaffold were tested. Then, the
      scaffolds were used to reconstruct the ACL in China Bama mimi pigs. At 24 weeks
      post-operation, the mechanical properties and histology of the regenerated ACL
      were analyzed. The maximum load and tensile strength were 472.43+/- 15.2 N and
      29.71+/- 0.96 MPa, respectively; both were ~75% of those of native ACL and ~90%
      of those of fiber scaffold. This indicated that the scaffold maintained a large
      portion of native ACL's mechanical properties, and tissue formation on the
      scaffold compensated most of the tensile strength loss caused by scaffold
      degradation. Histology and immunohistology analysis showed the morphology and
      major extracellular matrix components of the regenerated ligament resembled the
      native ACL. Thus, the Col-I/PVA blend fiber ACL scaffold showed good potential
      for clinical applications.

PMID- 23531981
TI  - Understanding geographic origins and history of admixture among chimpanzees in
      European zoos, with implications for future breeding programmes.
AB  - Despite ample focus on this endangered species, conservation planning for
      chimpanzees residing outside Africa has proven a challenge because of the lack of
      ancestry information. Here, we analysed the largest number of chimpanzee samples
      to date, examining microsatellites in >100 chimpanzees from the range of the
      species in Africa, and 20% of the European zoo population. We applied the
      knowledge about subspecies differentiation throughout equatorial Africa to assign
      origin to chimpanzees in the largest conservation management programme globally.
      A total of 63% of the genotyped chimpanzees from the European zoos could be
      assigned to one of the recognized subspecies. The majority being of West African
      origin (40%) will help consolidate the current breeding programme for this
      subspecies and the identification of individuals belonging to the two other
      subspecies so far found in European zoos can form the basis for breeding
      programmes for these. Individuals of various degree of mixed ancestry made up 37%
      of the genotyped European zoo population and thus highlight the need for
      appropriate management programmes guided by genetic analysis to preserve maximum
      genetic diversity and reduce hybridization among subspecies.

PMID- 23531982
TI  - On the origin of sweet potato (Ipomoea batatas (L.) Lam.) genetic diversity in
      New Guinea, a secondary centre of diversity.
AB  - New Guinea is considered the most important secondary centre of diversity for
      sweet potato (Ipomoea batatas). We analysed nuclear and chloroplast genetic
      diversity of 417 New Guinea sweet potato landraces, representing agro
      morphological diversity collected throughout the island, and compared this
      diversity with that in tropical America. The molecular data reveal moderate
      diversity across all accessions analysed, lower than that found in tropical
      America. Nuclear data confirm previous results, suggesting that New Guinea
      landraces are principally derived from the Northern neotropical genepool (Camote
      and Batata lines, from the Caribbean and Central America). However, chloroplast
      data suggest that South American clones (early Kumara line clones or, more
      probably, later reintroductions) were also introduced into New Guinea and then
      recombined with existing genotypes. The frequency distribution of pairwise
      distances between New Guinea landraces suggests that sexual reproduction, rather
      than somaclonal variation, has played a predominant role in the diversification
      of sweet potato. The frequent incorporation of plants issued from true seed by
      farmers, and the geographical and cultural barriers constraining crop diffusion
      in this topographically and linguistically heterogeneous island, has led to the
      accumulation of an impressive number of variants. As the diversification of sweet
      potato in New Guinea is primarily the result of farmers' management of the
      reproductive biology of their crop, we argue that on-farm conservation programmes
      that implement distribution of core samples (clones representing the useful
      diversity of the species) and promote on-farm selection of locally adapted
      variants may allow local communities to fashion relatively autonomous strategies
      for coping with ongoing global change.

PMID- 23531983
TI  - Nanotopography-mediated reverse uptake for siRNA delivery into neural stem cells
      to enhance neuronal differentiation.
AB  - RNA interference (RNAi) for controlling gene expression levels using siRNA or
      miRNA is emerging as an important tool in stem cell biology. However, the
      conventional methods used to deliver siRNA into stem cells result in significant
      cytotoxicity and undesirable side-effects. To this end, we have developed a
      nanotopography-mediated reverse uptake (NanoRU) delivery platform to demonstrate
      a simple and efficient technique for delivering siRNA into neural stem cells
      (NSCs). NanoRU consists of a self-assembled silica nanoparticle monolayer coated
      with extracellular matrix proteins and the desired siRNA. We use this technique
      to efficiently deliver siRNA against the transcription factor SOX9, which acts as
      a switch between neuronal and glial fate of NSCs. The knockdown of SOX9 enhanced
      the neuronal differentiation and decreased the glial differentiation of the NSCs.
      Our NanoRU platform demonstrates a novel application and the importance of
      nanotopography-mediated siRNA delivery into stem cells as an effective method for
      genetic manipulation.

PMID- 23531984
TI  - Internet-based photoaging within Australian pharmacies to promote smoking
      cessation: randomized controlled trial.
AB  - BACKGROUND: Tobacco smoking leads to death or disability and a drain on national
      resources. The literature suggests that cigarette smoking continues to be a major
      modifiable risk factor for a variety of diseases and that smokers aged 18-30
      years are relatively resistant to antismoking messages due to their widely held
      belief that they will not be lifelong smokers. OBJECTIVE: To conduct a randomized
      controlled trial (RCT) of a computer-generated photoaging intervention to promote
      smoking cessation among young adult smokers within a community pharmacy setting.
      METHODS: A trial was designed with 80% power based on the effect size observed in
      a published pilot study; 160 subjects were recruited (80 allocated to the control
      group and 80 to the intervention group) from 8 metropolitan community pharmacies
      located around Perth city center in Western Australia. All participants received
      standardized smoking cessation advice. The intervention group participants were
      also digitally photoaged by using the Internet-based APRIL Face Aging software so
      they could preview images of themselves as a lifelong smoker and as a nonsmoker.
      Due to the nature of the intervention, the participants and researcher could not
      be blinded to the study. The main outcome measure was quit attempts at 6-month
      follow-up, both self-reported and biochemically validated through testing for
      carbon monoxide (CO), and nicotine dependence assessed via the Fagerstrom scale.
      RESULTS: At 6-month follow-up, 5 of 80 control group participants (6.3%)
      suggested they had quit smoking, but only 1 of 80 control group participants
      (1.3%) consented to, and was confirmed by, CO validation. In the intervention
      group, 22 of 80 participants (27.5%) reported quitting, with 11 of 80
      participants (13.8%) confirmed by CO testing. This difference in biochemically
      confirmed quit attempts was statistically significant (chi(2) 1=9.0, P=.003). A
      repeated measures analysis suggested the average intervention group smoking
      dependence score had also significantly dropped compared to control participants
      (P<.001). These differences remained statistically significant after adjustment
      for small differences in gender distribution and nicotine dependence between the
      groups. The mean cost of implementing the intervention was estimated at AU $5.79
      per participant. The incremental cost-effectiveness ratio was AU $46 per
      additional quitter. The mean cost that participants indicated they were willing
      to pay for the digital aging service was AU $20.25 (SD 15.32). CONCLUSIONS:
      Demonstrating the detrimental effects on facial physical appearance by using a
      computer-generated simulation may be both effective and cost-effective at
      persuading young adult smokers to quit. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry: ACTRN12609000885291;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1260900088529
      (Archived by WebCite at http://www.webcitation.org/6F2kMt3kC).

PMID- 23531985
TI  - Diabetic nephropathy: lessons from the mouse.
AB  - BACKGROUND: A fundamental problem in the identification of new molecular targets
      for therapeutic intervention in diabetic nephropathy has been the lack of an
      experimental mouse model that faithfully recapitulates human diabetic
      nephropathy. METHODS: Our laboratory, in collaboration with Drs Kakoki and
      Smithies at the University of North Carolina-Chapel Hill, has developed novel
      strains of Akita diabetic mice in which the p66 longevity gene has been deleted
      by homologous recombination. We chose to delete p66 because p66 controls
      mitochondrial metabolism and cellular responses to oxidative stress, aging, and
      apoptosis. The redox function of p66 is indispensable for the exponential
      increase in reactive oxygen species (ROS) associated with diabetes. RESULTS: p66
      null Akita mice express a protection phenotype in kidneys that includes marked
      attenuation of oxidative stress and glomerular/tubular injury and a striking
      reduction in urine albumin excretion. Furthermore, the p66 null mutation not only
      confers a survival advantage to podocytes but also prevents foot process
      effacement and retains the stationary phenotype. Sirtuin 1 (SIRT1) deacetylase
      and p66 share overlapping biological functions but induce divergent phenotypes,
      including opposite effects on longevity, ROS metabolism, cell senescence, and
      apoptosis. Exciting new data from our laboratory show that SIRT1 is upregulated
      in the kidneys of p66 null Akita mice and decreases acetylation of p53, which
      destabilizes the p53 protein and prevents the transcription of p53 proapoptosis
      genes. Conversely, SIRT1 activates the transcription of FOXO3a-dependent stress
      gene programs that detoxify ROS and promote the survival phenotype. CONCLUSION:
      We will focus future research on translating these experimental findings in the
      mouse to clinical diabetic nephropathy.

PMID- 23531986
TI  - Origins of the beta-lactam rings in natural products.
AB  - Naturally occurring beta-lactam compounds fall into four basic structural groups,
      the penicillins/cephalosporins, the clavams, the carbapenems and the monocyclic
      beta-lactams. Biosynthetic studies have clarified the steps involved in the
      formation of the beta-lactam ring for the first three of these groups, but the
      corresponding process or processes for the monocyclic beta-lactams remains
      obscure. Isopenicillin N synthase is responsible for formation of the beta-lactam
      ring in all penicillin/cephalosporin compounds, and the reaction catalyzed is
      completely separate from that of beta-lactam synthetase, the enzyme responsible
      for ring formation in all clavam compounds. Conversely, carbapenam synthetase,
      the enzyme responsible for beta-lactam ring formation for all carbapenem
      compounds, shows clear relatedness to beta-lactam synthetase, despite differences
      in the substrates and the products for the two enzymes. The mechanism of ring
      formation has not yet been clarified for any of the monocyclic beta-lactams, but
      a third distinct mechanism of beta-lactam ring formation seems likely, and this
      group includes such a diverse collection of structures that even more new ring
      forming reactions may be involved. 

PMID- 23531987
TI  - Isolation of new polyketide metabolites, linearolides A and B, from Streptomyces
      sp. RK95-74.
AB  - Although all Streptomyces strains are now thought to have 20-30 gene clusters for
      secondary metabolite biosynthesis, we cannot actually identify so many kinds of
      metabolites from one strain by conventional methods. Using Streptomyces sp. RK95
      74, previously found as a cytotrienin producer, we searched new metabolites other
      than cytotrienin derivatives. Following the cultivation with new media and the
      peak-guided fractionation, we have found new compounds with new polyketide
      scaffold, named linearolides A and B. 

PMID- 23531988
TI  - Diepoxyactinorhodin: a new pyranonaphthoquinone dimer from Streptomyces sp.

PMID- 23531989
TI  - Anti-MRSA drug use and antibiotic susceptibilities of MRSA at a university
      hospital in Japan from 2007 to 2011.
AB  - The purpose of this study is to examine the use of anti-methicillin-resistant
      Staphylococcus aureus (MRSA) drugs, such as vancomycin (VCM), teicoplanin (TEIC),
      arbekasin (ABK) and linezolid (LZD), and the antibiotic susceptibilities of MRSAs
      in Kobe University Hospital. We investigated MRSA isolation and use of anti-MRSA
      drugs and susceptibilities of MRSA, using linear regression analysis, from 2007
      to 2011, and checked for correlation between the use of these drug and the
      antibiotic susceptibilities of MRSA. The overall monthly isolation rates of MRSA
      decreased from a mean of 84.8% in 2007 to 70.0% in 2011 (r=0.946, P=0.015, b=
      0.220), and the monthly isolation rate of MRSA in inpatients decreased from a
      mean of 78.6% in 2007 to 57.7% in 2011 (r=0.952, P=0.012, b=-0.160). From 2007 to
      2011, VCM consumption significantly increased (r=0.916, P=0.029, b=0.055),
      whereas TEIC and LZD use remained stable during the study period. In addition,
      ABK use significantly decreased from 23.8 defined daily dose (DDD) per 1000
      patient-days in 2007 to 5.2 DDD per 1000 in 2011 (r=0.902, P=0.036, b=-0.216).
      Susceptibility rates of MRSA were almost 100% to TEIC and VCM. The rates of MRSA
      to ABK and LZD significantly increased (r=0.959, P=0.010, b=2.137 for ABK and
      r=0.933, P=0.020, b=3.111 for LZD). In conclusion, our findings indicated a
      decreased MRSA isolation rate and the effective use of anti-MRSA drugs (VCM,
      TEIC, ABK and LZD), and improved susceptibility rates to anti-MRSA drugs,
      suggesting the possibilities that appropriate and early use of anti-MRSA drugs
      may cause the decrease of MRSA isolation.

PMID- 23531990
TI  - Three eremophilane derivatives, MBJ-0011, MBJ-0012 and MBJ-0013, from an
      endophytic fungus Apiognomonia sp. f24023.

PMID- 23531991
TI  - A 33-year-old woman with fever, obtundation and diarrhea.

PMID- 23531992
TI  - Diffuse idiopathic skeletal hyperostosis and familial hypocalciuric
      hypercalcemia: a unique association in a young female.
AB  - Familial hypocalciuric hypercalcemia (FHH) is a cause of lifelong hypercalcemia
      resulting from inactivated mutations in the calcium sensing receptor gene.
      Diffuse idiopathic skeletal hyperostosis (DISH) is an under diagnosed condition
      that leads to ossification of ligaments and entheses of the spine and peripheral
      skeleton. We describe a 45-year-old diabetic woman with hypercalcemia secondary
      to FHH who developed dysphagia because of external esophageal compression from
      DISH. The patient had no additional identifiable risk factors for DISH except for
      diabetes mellitus. An association between FHH and DISH has not been previously
      reported. Although most cases of hypercalcemia are found to have decreased bone
      mineralization, inactivation of calcium sensing receptor may induce a
      promitogenic response to hypercalcemia resulting in increased bone density.
      However, a causal association between FHH and DISH remains unproven.

PMID- 23531993
TI  - Renal sarcoidosis with limited lung manifestations expressing Propionibacterium
      acnes antigens in the affected tubulointerstitium.
AB  - Sarcoidosis is a granulomatous multisystemic disorder of unknown origin that can
      affect the kidneys. Previous reports from Japan and Europe have indicated a link
      between Propionibacterium acnes infections and sarcoidosis. Here, we present the
      case of a 68-year-old woman with hypercalcemia and renal failure. A kidney biopsy
      was performed, which showed granulomatous tubulointerstitial nephritis with a
      large nonnecrotic nodule that contained mononuclear inflammatory cells and
      multinucleated giant cells. Subsequent immunohistochemical analysis revealed
      intracytoplasmic structures, which strongly indicated the presence of the P acnes
      antigen. Treatment with methylprednisolone ameliorated the patient's
      hypercalcemia and renal failure. This case report emphasizes the potential of
      chronic P acnes infection to cause sarcoidosis.

PMID- 23531994
TI  - Risk of nocardial infections with anti-tumor necrosis factor therapy.
AB  - Anti-tumor necrosis factor (anti-TNF) therapy is beneficial in the management of
      many chronic immune-mediated inflammatory diseases. However, its use is
      associated with increased risk of bacterial, fungal and viral infections. We
      present a case of cutaneous nocardiosis that occurred in a 61-year-old man, whose
      Crohn's disease was treated for nearly 1.5 years with infliximab. Prompt therapy
      with trimethoprim-sulfamethoxazole led to complete resolution. Only few cases of
      nocardiosis complicating anti-TNF therapy are reported in the literature. We
      present the case report and summary of the available literature with updates on
      the management and the treatment of the disease.

PMID- 23531995
TI  - Controlling the rate of coiled coil driven membrane fusion.
AB  - Sets of complementary lipidated coiled-coil forming peptides that fuse membrane
      fusion have been designed. The influence of the coiled-coil motif on the rate of
      liposome fusion was studied, by varying the number of heptad repeats. We found
      that an increased coiled-coil stability of complementary peptides translates into
      increased rates of membrane fusion of liposomes.

PMID- 23531996
TI  - Evaluation of osteogenic cell culture and osteogenic/peripheral blood mononuclear
      human cell co-culture on modified titanium surfaces.
AB  - This study aimed to determine the effect of a bioactive ceramic coating on
      titanium in the nanothickness range on human osteogenic cells, peripheral blood
      mononuclear cells (PBMC) and on osteogenic cells co-cultured with PBMC without
      exogenous stimuli. Cell viability, proliferation, adhesion, cytokine release
      (IL1beta, TGFbeta1, IL10 and IL17) and intracellular stain for osteopontin and
      alkaline phosphatase were assessed. Morphologic evaluation showed smaller and
      less spread cell aspects in co-culture relative to osteogenic cell culture. Cell
      viability, proliferation and adhesion kinetics were differently influenced by
      surface texture/chemistry in culture versus co-culture. Cytokine release was also
      influenced by the interaction between mononuclear and osteogenic cells (mediators
      released by mononuclear cells acted on osteogenic cells and vice versa). In
      general, 'multi-cell type' interactions played a more remarkable role than the
      surface roughness or chemistry utilized on the in vitro cellular events related
      to initial stages of bone formation.

PMID- 23531997
TI  - Reliable contact fabrication on nanostructured Bi2Te3-based thermoelectric
      materials.
AB  - A cost-effective and reliable Ni-Au contact on nanostructured Bi2Te3-based alloys
      for a solar thermoelectric generator (STEG) is reported. The use of MPS SAMs
      creates a strong covalent binding and more nucleation sites with even
      distribution for electroplating contact electrodes on nanostructured
      thermoelectric materials. A reliable high-performance flat-panel STEG can be
      obtained by using this new method.

PMID- 23531998
TI  - Effect of antioxidant supplementation on surrogate markers of fibrosis in chronic
      pancreatitis: a randomized, placebo-controlled trial.
AB  - OBJECTIVES: This study aimed to determine the effect of antioxidant (AO)
      supplementation on surrogate markers of fibrosis in patients with chronic
      pancreatitis (CP). METHODS: In a randomized, placebo (PL)-controlled trial,
      patients with CP were randomized to groups that were given PL or AO for 3 months.
      Outcome measures were change in serum levels of transforming growth factor beta1
      and platelet-derived growth factor AA (PDGF-AA) (primary outcome) as well as
      blood markers of oxidative stress (thiobarbituric acid-reactive substances) and
      AO status (ferric-reducing ability of plasma) (secondary outcome). Pain relief
      and analgesic requirement was also recorded. RESULTS: Patients (n = 61; mean [SD]
      age, 35.2 [10.0]; male patients, 43) were assigned to AO (n = 31) and PL (n = 30)
      groups. The median (range) percent reduction from baseline to 3 months in levels
      of PDGF-AA (17.1% [-25.3% to 88.7%] vs 2.8% [-243.1% to 30.2%]; P = 0.001),
      transforming growth factor beta1 (P = 0.573), and thiobarbituric acid-reactive
      substances (P = 0.207) as well as percent increment from baseline to 3 months in
      ferric-reducing ability of plasma (P = 0.003) were higher in the AO group
      compared with the PL group. Proportion of patients who had both reduced PDGF-AA
      and reduced pain was greater in AO as compared with PL group (17/31 vs 9/30, P =
      0.05) CONCLUSIONS: Reduction in markers of fibrosis (PDGF-AA) translated into
      clinical outcome (reduction in pain and analgesic requirements) in those
      supplemented with AOs in CP (trial registration, CTRI/2011/05/001747).

PMID- 23531999
TI  - Contrast-enhanced ultrasound in the differential diagnosis of exocrine versus
      neuroendocrine pancreatic tumors.
AB  - OBJECTIVES: Contrast-enhanced ultrasound (CEUS) has been developed to better
      characterize the microvasculature of solid masses in several organs, including
      the pancreas. In this study, we assessed CEUS accuracy in differentiating
      exocrine from endocrine pancreatic tumors. METHODS: A total of 127 patients with
      single, undetermined pancreatic masses were prospectively examined with
      transabdominal ultrasound and CEUS, before surgical resection or percutaneous
      biopsy. RESULTS: Exocrine and endocrine pancreatic tumors showed different
      intralesional vascularization patterns: 98.9% (90/91) of exocrine tumors were
      hypoenhancing, whereas 95.8 % (23/24) of endocrine tumors had a hypervascular
      supply. A hypoenhancing pattern, indicative of ductal adenocarcinoma, had a
      significant (P < 0.001) diagnostic accuracy of 91.3% with a sensitivity of 96.8%,
      a specificity of 85.3%, a positive predictive value and a negative predictive
      value of 94.7% and 90.6%, respectively. The hyperenhancing pattern, indicative of
      endocrine tumors, had a significant (P = 0.031) diagnostic accuracy of 73.8% with
      a sensitivity of 83.3%, a specificity of 60.0%, a positive predictive value and
      negative predictive value of 83.3% and 60.0%, respectively. CONCLUSIONS: Contrast
      enhanced ultrasound has a valuable diagnostic accuracy in differentiating
      exocrine from endocrine pancreatic tumors, which is a fundamental step to address
      appropriate histological evaluation, therapeutic approach, and follow-up.

PMID- 23532000
TI  - Aggressive surgery for borderline resectable pancreatic cancer: evaluation of
      National Comprehensive Cancer Network guidelines.
AB  - OBJECTIVES: The objective of this study was to evaluate the relevance of defining
      borderline resectable (BR) pancreatic cancer as a distinct entity in the
      treatment scheme of pancreatic cancer as proposed by the National Comprehensive
      Cancer Network. METHODS: Among 375 patients with pancreatic cancer, 137 patients
      were deemed to have resectable disease (R) by preoperative imaging studies,
      whereas 96 were found to have an unresectable disease during surgery. The
      remaining 142 patients fulfilled the definition of BR and were further classified
      into 3 subgroups based on the National Comprehensive Cancer Network guidelines:
      portal vein invasion (PV[+]), common hepatic artery invasion (CHA[+]), and
      superior mesenteric artery invasion (SMA[+]). PV(+) was subdivided into types B,
      C, and D according to the degree of portal vein invasion. RESULTS: Patients in
      the R group had significantly better survival than those in the PV(+) group (P =
      0.0038), who in turn survived significantly longer than those classified as
      SMA(+) (P = 0.041). Type B patients survived significantly longer than did types
      C and D patients (P = 0.013 and P = 0.030, respectively). In PV(+) patients,
      compliance with postoperative chemotherapy at 3 and 6 months was 56.9% and 44.6%,
      respectively, substantially inferior to patients with resectable disease (72.6%
      and 54.7%, respectively). CONCLUSIONS: The optimal treatment strategy may differ
      among various subgroups within the BR category.

PMID- 23532002
TI  - Analysis of visible-light-active Sn(II)-TiO2 photocatalysts.
AB  - The influence of Sn(II) species on TiO2 is investigated. The absorption spectra
      of these materials are red-shifted by 115 nm to the visible region of the solar
      spectrum compared with P25 TiO2. This prominent red-shift is attributed to the
      interaction of Sn(II) 5s orbitals with the TiO2 decreasing the band gap of TiO2
      by raising its valence band. The tin oxidation state and the materials electronic
      structure are evaluated using Mossbauer spectroscopy and valence band X-ray
      photoelectron spectroscopy respectively. These materials are active for
      sacrificial photo-generation of hydrogen in visible light.

PMID- 23532001
TI  - Risk models for post-endoscopic retrograde cholangiopancreatography pancreatitis
      (PEP): smoking and chronic liver disease are predictors of protection against
      PEP.
AB  - OBJECTIVES: We investigated which variables independently associated with
      protection against or development of postendoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis (PEP) and severity of PEP.
      Subsequently, we derived predictive risk models for PEP. METHODS: In a case
      control design, 6505 patients had 8264 ERCPs, 211 patients had PEP, and 22
      patients had severe PEP. We randomly selected 348 non-PEP controls. We examined 7
      established- and 9 investigational variables. RESULTS: In univariate analysis, 7
      variables predicted PEP: younger age, female sex, suspected sphincter of Oddi
      dysfunction (SOD), pancreatic sphincterotomy, moderate-difficult cannulation
      (MDC), pancreatic stent placement, and lower Charlson score. Protective variables
      were current smoking, former drinking, diabetes, and chronic liver disease (CLD,
      biliary/transplant complications). Multivariate analysis identified seven
      independent variables for PEP, three protective (current smoking, CLD-biliary,
      CLD-transplant/hepatectomy complications) and 4 predictive (younger age,
      suspected SOD, pancreatic sphincterotomy, MDC). Pre- and post-ERCP risk models of
      7 variables have a C-statistic of 0.74. Removing age (seventh variable) did not
      significantly affect the predictive value (C-statistic of 0.73) and reduced model
      complexity. Severity of PEP did not associate with any variables by multivariate
      analysis. CONCLUSIONS: By using the newly identified protective variables with 3
      predictive variables, we derived 2 risk models with a higher predictive value for
      PEP compared to prior studies.

PMID- 23532003
TI  - Photostimulated near-infrared persistent luminescence as a new optical read-out
      from Cr3+-doped LiGa5O8.
AB  - In conventional photostimulable storage phosphors, the optical information
      written by x-ray or ultraviolet irradiation is usually read out as a visible
      photostimulated luminescence (PSL) signal under the stimulation of a low-energy
      light with appropriate wavelength. Unlike the transient PSL, here we report a new
      optical read-out form, photostimulated persistent luminescence (PSPL) in the near
      infrared (NIR), from a Cr(3+)-doped LiGa5O8 NIR persistent phosphor exhibiting a
      super-long NIR persistent luminescence of more than 1,000 h. An intense PSPL
      signal peaking at 716 nm can be repeatedly obtained in a period of more than
      1,000 h when an ultraviolet-light (250-360 nm) pre-irradiated LiGa5O8:Cr(3+)
      phosphor is repeatedly stimulated with a visible light or a NIR light. The
      LiGa5O8:Cr(3+) phosphor has promising applications in optical information
      storage, night-vision surveillance, and in vivo bio-imaging.

PMID- 23532004
TI  - Relationship of early-onset baldness to prostate cancer in African-American men.
AB  - BACKGROUND: Early-onset baldness has been linked to prostate cancer; however,
      little is known about this relationship in African-Americans who are at elevated
      prostate cancer risk. METHODS: We recruited 219 African-American controls and 318
      African-American prostate cancer cases. We determined age-stratified associations
      of baldness with prostate cancer occurrence and severity defined by high stage
      (T3/T4) or high grade (Gleason 7+.) Associations of androgen metabolism genotypes
      (CYP3A4, CYP3A5, CYP3A43, AR-CAG, SRD5A2 A49T, and SRD5A2 V89L), family history,
      alcohol intake, and smoking were examined by baldness status and age group by
      using multivariable logistic regression models. RESULTS: Baldness was associated
      with odds of prostate cancer [OR = 1.69; 95% confidence interval (CI), 1.05
      2.74]. Frontal baldness was associated with high-stage (OR = 2.61; 95% CI, 1.10
      6.18) and high-grade (OR = 2.20; 95% CI, 1.05-4.61) tumors. For men diagnosed
      less than the age of 60 years, frontal baldness was associated with high stage
      (OR = 6.51; 95% CI, 2.11-20.06) and high grade (OR = 4.23; 95% CI, 1.47-12.14).
      We also observed a suggestion of an interaction among smoking, median age, and
      any baldness (P = 0.02). CONCLUSIONS: We observed significant associations
      between early-onset baldness and prostate cancer in African-American men.
      Interactions with age and smoking were suggested in these associations. Studies
      are needed to investigate the mechanisms influencing the relationship between
      baldness and prostate cancer in African-American men. IMPACT: African-American
      men present with unique risk factors including baldness patterns that may
      contribute to prostate cancer disparities.

PMID- 23532005
TI  - Spanish-speaking patients' engagement in interactive voice response (IVR) support
      calls for chronic disease self-management: data from three countries.
AB  - We measured Spanish-speaking patients' engagement in Interactive Voice Response
      (IVR) calls using data from self-management support studies in Honduras, Mexico
      and the US. A total of 268 patients with diabetes or hypertension participated in
      6-12 weeks of weekly IVR follow-up. Participants had an average of 6.1 years of
      education, and 73% of them were women. After 2443 person-weeks of follow-up,
      patients had completed 1494 IVR assessments. The call completion rates were
      higher in the US (75%) than in Honduras (59%) or Mexico (61%; P < 0.001).
      Patients participating with an informal caregiver were more likely to complete
      calls (adjusted odds ratio 1.5; P = 0.03) while patients reporting fair or poor
      health at enrolment were less likely (adjusted odds ratio 0.59; P = 0.02).
      Satisfaction rates were high, with 98% of patients reporting that the system was
      easy to use, and 86% reporting that the calls helped them a great deal in
      managing their health problems. IVR self-management support is feasible among
      Spanish-speaking patients with chronic disease, including those living in less
      developed countries. Involving informal caregivers may increase patient
      engagement.

PMID- 23532010
TI  - Malignant emboli on transcranial Doppler during carotid stenting predict
      postprocedure diffusion-weighted imaging lesions.
AB  - BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) has a higher
      incidence of periprocedural stroke compared with endarterectomy. Identifying CAS
      steps with the highest likelihood of embolization may have important
      implications. We evaluated CAS safety by correlating the findings of procedural
      transcranial Doppler with postprocedure diffusion-weighted imaging (DWI) lesions.
      METHODS: In this prospective study, transcranial Doppler monitoring was performed
      during CAS procedures, which were divided into 11 steps. Embolic signals on
      transcranial Doppler were counted and classified based on the relative energy
      index of microembolic signals into microemboli <= 1 or malignant macroemboli >1.
      Poststenting MRI was performed in all cases. A negative binomial regression model
      was used to evaluate the predictive value of transcranial Doppler emboli for new
      DWI lesions. RESULTS: Thirty subjects were enrolled. Seven of 30 subjects (23.3%)
      were asymptomatic. The median embolic signal count was 212.5 (108 microemboli and
      80 malignant macroemboli). Stent deployment phase showed the highest median
      embolic signals count at 58, followed by protection device deployment at 30
      (P=0.0006). Twenty-four of 30 (80%) had new DWI lesions on post-CAS MRI. The
      median DWI count was 4 (interquartile range 7). Two of 30 (6.7%) had new or
      worsening clinical deficits post-CAS. For every malignant embolus, the expected
      count of DWI lesions increases by 1% ( 95% confidence interval, 0%-2%; P=0.032).
      CONCLUSIONS: We observed a high incidence of embolic signals during CAS
      procedure, especially, when devices were deployed. Most subjects developed new
      DWI lesions, but only 6.7% had deficits. Malignant macroemboli predicted new DWI
      lesions.

PMID- 23532011
TI  - Efficacy of coupling inhibitory and facilitatory repetitive transcranial magnetic
      stimulation to enhance motor recovery in hemiplegic stroke patients.
AB  - BACKGROUND AND PURPOSE: Although there has been extensive research on the
      effectiveness of repetitive transcranial magnetic stimulation (rTMS) to improve
      patients' motor performance after experiencing chronic stroke, explicit findings
      on the coupling of different rTMS protocols are meager. We designed this sham
      controlled randomized study to investigate the potential for a consecutive
      suppressive-facilitatory TMS protocol to improve motor outcomes after chronic
      stroke. METHODS: Fifty-four chronic hemiplegic stroke patients were allocated
      across 4 groups to undergo 20 daily sessions of (1) 1 Hz rTMS over the
      contralesional primary motor cortex (M1) and then intermittent theta burst
      stimulation over the ipsilesional M1 (group A); (2) contralesional sham
      stimulation and then ipsilesional real intermittent theta burst stimulation
      (group B); (3) contralesional real 1 Hz rTMS and then ipsilesional sham
      stimulation (group C); or (4) bilateral sham-control procedures (group D). We
      tested cortical excitability and motor activity assessments at the baseline,
      postpriming rTMS, and postconsequent rTMS periods. RESULTS: At post, group A
      showed greater muscle strength, Fugl-Meyer Assessment (FMA), Wolf Motor Function
      test, and reaction time improvement in comparison with group B (P<0.001~0.003)
      and group C (P=0.001~0.003). Correlation analyses in group A revealed a close
      relation between contralesional map area decrement and Wolf Motor Function test
      gain (P=0.005; r=-0.75), and also revealed ipsilesional map area increment and
      reaction time decrement (P=0.02; r=-0.87). We detected no such relations in the
      other 3 groups. CONCLUSIONS: Our clinical trials established an extended
      timeframe during which conditioning could be safely continued and produced more
      favorable outcomes in facilitating motor performance and ameliorating
      interhemispheric imbalance than those obtained from single-course rTMS modulation
      alone.

PMID- 23532012
TI  - Risk factors for intracerebral hemorrhage: the REasons for geographic and racial
      differences in stroke (REGARDS) study.
AB  - BACKGROUND AND PURPOSE: Risk factors for intracerebral hemorrhage (ICH) have been
      largely identified in case-control studies, with few longitudinal studies
      available. METHODS: Predictors of incident ICH among 27 760 black and white
      participants from the REasons for Geographic And Racial Differences in Stroke
      (REGARDS) cohort study were assessed. RESULTS: There were 62 incident ICH events
      during an average follow-up of 5.7 years. The increase in risk with age differed
      substantially between blacks and whites (P=0.006), with a 2.25-fold (95%
      confidence interval, 1.63-3.12) increase per decade in whites, but no age
      association with ICH risk in blacks (hazard ratio=1.09; 95% confidence interval,
      0.70-1.68). We observed increased risk among men, those with higher systolic
      blood pressure, and warfarin users. CONCLUSIONS: The racial differences in the
      impact of age contributed to a risk of ICH that was >5 times higher for blacks
      than whites at age 45, but only about one third as great by age 85. Confirming
      findings from other studies, men participants with elevated systolic blood
      pressure and warfarin users were also at greater risk. The contributors to the
      racial differences in ICH risk require additional investigation.

PMID- 23532013
TI  - Letter by Gomez-Choco and Valdueza regarding article, "posterior cerebral artery
      laterality on magnetic resonance angiography predicts functional outcome".

PMID- 23532014
TI  - Validation of the ABCD3-I score to predict stroke risk after transient ischemic
      attack.
AB  - BACKGROUND AND PURPOSE: The Age, Blood Pressure, Clinical Features, Duration, and
      Diabetes plus Dual TIA (ABCD(3)-I) score is recommended to predict the risk of
      early stroke after transient ischemic attack. The aim of this study was to
      validate the predictive value of the ABCD(3)-I score and compare the accuracy of
      the Age, Blood Pressure, Clinical Features, Duration, and Diabetes (ABCD(2)) and
      ABCD(3)-I scores in a Chinese population. METHODS: Data were prospectively
      collected from patients who had transient ischemic attack, as defined by the
      World Health Organization time-based criteria. ABCD(2) and ABCD(3)-I scores were
      available within 7 days of the index transient ischemic attack. The predictive
      outcome was stroke occurrence at 90 days. The receiver-operating characteristic
      curves were plotted, and the C statistics were calculated as a measure of
      predictive ability. The comparison of the area under the receiver-operating
      characteristic curve (area under the curve) was performed by Z test. RESULTS:
      Among 239 eligible patients, the mean age was 57.4+/-13.32 years, and 40.2% of
      the patients were women. The incidence of stroke at 90 days was 12.1%, which
      ranged from 0% in patients with lower ABCD(3)-I scores (0-3) to 40.91% in those
      with higher scores of 8 to 13 (P for trend <0.0001). Moreover, the C statistic of
      ABCD(3)-I scores (0.825; 95% confidence interval, 0.752-0.898) was statistically
      higher than that of ABCD(2) scores (0.694; 95% confidence interval, 0.601-0.786;
      P<0.001). CONCLUSIONS: The ABCD(3)-I score had a higher predictive value than the
      ABCD(2) score for assessing the risk of early stroke after transient ischemic
      attack in a Chinese population.

PMID- 23532015
TI  - Letter by Lanterna et al regarding article, "endovascular treatment of
      intracranial aneurysms with flow-diverters, a meta-analysis".

PMID- 23532017
TI  - Foreword celebrating the career of professor Kuniaki Tatsuta.

PMID- 23532016
TI  - Natural killer cell inhibitory receptor expression in humans and mice: a closer
      look.
AB  - The Natural Killer (NK) cell population is composed of subsets of varying sizes
      expressing different combinations of inhibitory receptors for MHC class I
      molecules. Genes within the NK gene complex, including the inhibitory receptors
      themselves, seem to be the primary intrinsic regulators of inhibitory receptor
      expression, but the MHC class I background is an additional Modulating factor. In
      this paper, we have performed a parallel study of the inhibitory receptor
      repertoire in inbred mice of the C57Bl/6 background and in a cohort of 44 humans.
      Deviations of subset frequencies from the "product rule (PR)," i.e., differences
      between observed and expected frequencies of NK cells, were used to identify MHC
      independent and MHC-dependent control of receptor expression frequencies. Some
      deviations from the PR were similar in mice and humans, such as the decreased
      presence of NK cell subset lacking inhibitory receptors. Others were different,
      including a role for NKG2A in determining over- or under-representation of
      specific subsets in humans but not in mice. Thus, while human and murine
      inhibitory receptor repertoires differed in details, there may also be shared
      principles governing NK cell repertoire formation in these two species.

PMID- 23532018
TI  - Prologue to the special issue on synthesis.

PMID- 23532019
TI  - Total synthesis of the big four antibiotics and related antibiotics.
AB  - The first total syntheses of a variety of antibiotics have been accomplished by
      using carbohydrates as a chiral source. The key target molecules were members of
      the 'Big Four' classes of antibiotics (macrolides, aminoglycosides, beta-lactams
      and tetracyclines), naphthoquinone antibiotics and their related antibiotics.

PMID- 23532020
TI  - A practical preparation of the key intermediate for penems and carbapenems
      synthesis.
AB  - A novel, practical and stereoselective synthesis of (3R,4R)-4-acetoxy-3-[(R)-1-(t
      butyldimethylsilyloxy)ethyl]-2-azetidinone, a key intermediate in the preparation
      of beta-lactam antibiotics is reported. The crucial step of the synthesis is
      based on the Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade between
      silyl protected (R)-3-butyn-2-ol and the nitrone derived from benzyl
      hydroxylamine and benzyl glyoxylate. The obtained adduct is subjected to
      debenzylation with sodium, or lithium in liquid ammonia followed by oxidation
      with lead tetraacetate to afford the final product.

PMID- 23532021
TI  - Novel semisynthetic antibiotics from caprazamycins A-G: caprazene derivatives and
      their antibacterial activity.
AB  - Acidic treatment of a mixture of caprazamycins (CPZs) A-G isolated from a screen
      of novel antimycobacterial agents gave caprazene, a core structure of CPZs, in
      high yield. Chemical modification of the resulting caprazene was performed to
      give its various derivatives. The structure-activity relationships of the
      caprazene derivatives against several mycobacterial species and pathogenic Gram
      positive and Gram-negative bacteria were studied. Although caprazene showed no
      antibacterial activity, the antibacterial activity was restored for its 1'''
      alkylamide, 1'''-anilide and 1'''-ester derivatives. Compounds 4b (CPZEN-45), 4d
      (CPZEN-48), 4f and 4g (CPZEN-51) exhibited more potent activities against
      Mycobacterium tuberculosis and M. avium complex strains than CPZ-B. These results
      suggest that caprazene would be a good precursor from which novel semisynthetic
      antibacterial antibiotics can be designed for the treatment of mycobacterial
      diseases such as tuberculosis and M. avium complex infection.

PMID- 23532023
TI  - Vaccinations: nursing response and responsibility.

PMID- 23532022
TI  - New dinapinone derivatives, potent inhibitors of triacylglycerol synthesis in
      mammalian cells, produced by Talaromyces pinophilus FKI-3864.
AB  - Eight new dinapinones, AB1, AB2, AC1, AC2, AD1, AD2, AE1 and AE2, were isolated
      from the culture broth of Talaromyces pinophilus FKI-3864. The structures of
      these dinapinones were elucidated by various NMR experiments. All these
      dinapinones possessed the same biaryl dihydronaphthopyranone skeleton consisting
      of a heterodimer with one monapinone A and one different monapinone. Dinapinones
      AB1 and AB2, consisting of monapinones A and B, were atropisomers. Similarly,
      dinapinones AC1 and AC2, consisting of monapinones A and C, dinapinones AD1 and
      AD2, consisting of monapinones A and D, and dinapinones AE1 and AE2, consisting
      of monapinones A and E, were atropisomers. Dinapinone AB2 showed potent
      inhibition of triacylglycerol (TG) synthesis in intact mammalian cells with an
      IC50 value of 1.17 MUM, whereas the other dinapinones showed weak inhibition of
      TG synthesis.

PMID- 23532024
TI  - NANN member shares reflections on the neonatal nurse practitioner profession.

PMID- 23532026
TI  - White matter injury in preterm infants: could human milk play a role in its
      prevention?
AB  - Human milk has been found to be beneficial for the development of all newborns.
      It is protective during the development of the gastrointestinal tract, important
      in neurologic development, immune system function, and nourishment. Human milk
      has a number of components that aid in the anti-inflammatory process and free
      radical reduction and is a building block for neurologic development. Cerebral
      white matter injury is a common occurrence in preterm infants. Results of this
      injury can be seen into early childhood and throughout the life of the
      individual. White matter injury most frequently occurs because of hypoxia and the
      inflammatory process, which often results in the injury of myelinating
      oligodendrites. This article proposes the potential importance of human milk in
      slowing and preventing cerebral white matter injury because of the components in
      human milk that affect the inflammatory and free radical reduction processes. It
      also proposes its ability to provide nutrients essential to myelin development.

PMID- 23532028
TI  - Simulation with synergy and community energy.
AB  - Neonatal nurse practitioners (NNPs) have a crucial role in the management and
      care of critically ill newborns and infants in the neonatal intensive care unit.
      Their role responsibilities range from daily management of care, oversight of
      unit and bedside education, execution of advanced procedures, and attendance at
      high-risk deliveries. During their educational program, there is a mix of
      didactic and clinical training. To ensure that their graduates are able to
      competently care for neonatal patients in the ever-advancing neonatal world, the
      NNP program at the University of Texas Medical Branch-Galveston (UTMB), has
      implemented simulation-based training into every clinical course. This article
      describes the history of simulation in the NNP program at UTMB, discusses the
      current use of simulation at UTMB, explores the synergistic use of undergraduate
      students in simulations at UTMB, and details the use of professional volunteers
      from the local medical community to execute the simulations and debriefing
      process.

PMID- 23532029
TI  - Bordetella pertussis infection in infants: a reemerging disease.
AB  - Bordetella pertussis is a highly contagious bacterial disease currently on the
      rise in the United States. The most vulnerable age group is infants younger than
      1 year old. The reasons for the current outbreak are multifactorial. The
      following is a case report describing a recent case of Bordetella pertussis
      infection admitted to a neonatal intensive care unit.

PMID- 23532030
TI  - What neonatal intensive care nurses need to know about neonatal palliative care.
AB  - The purpose of this study was to identify and prioritize topics for a
      professional development program in neonatal palliative care. A total of 276
      nurses and midwives who work in an Australian neonatal intensive care unit (NICU)
      and 26 international healthcare professionals working in NICU and palliative care
      served as participants. A Delphi technique was used, consisting of a series of
      rounds of data collection via interview and questionnaire, to identify and
      consolidate opinions of nurses and other healthcare professionals who work in
      neonatal intensive care units. The main outcome measures were: (1) Topics to be
      included in a professional development program for nurses working in neonatal
      intensive care units and (2) the preferred format of the program. Twenty-three
      high-priority topics were identified, which included preparing families when
      death is imminent, how to provide emotional support to grieving parents,
      advocating for a dying baby, and assessing and managing pain in a dying baby.
      Care of a dying infant requires the same skill set as caring for older terminally
      ill children internationally. A combination of face-to-face lectures and
      interactive workshops using case studies and audiovisual examples is the
      preferred format.

PMID- 23532031
TI  - Implementing family-integrated care in the NICU: a parent education and support
      program.
AB  - The purpose of this study was to develop, implement, and evaluate a parent
      education and support program that enhances family-integrated care in a Canadian
      neonatal intensive care unit (NICU). A total of 39 mothers of infants born at 35
      or fewer weeks' gestation were enrolled in the pilot program. We examined the
      development, implementation, and qualitative assessment of the education
      component of a family-integrated care program. We enrolled in groups of 4 or 5,
      the study mothers agreed to attend daily educational sessions, provide care for
      their infants for at least 8 hours daily, and participate in medical rounds. The
      educational sessions were provided by staff and veteran parents to assist
      parents' development of confidence in providing caregiving skills and assuming
      the role of a primary caregiver for their infants as they moved closer to
      discharge. Effectiveness of the program was evaluated through anecdotal feedback
      and a formal evaluation process at discharge. The results indicated that the
      mothers were provided with the tools to parent their infants in the NICU,
      recognize their own strengths, increase their problem-solving strategies, and
      emotionally prepare them to take their infant home. Feedback from the
      participants provided direction to adapt the program to provide optimal parent
      support and education. Parental education is a valued and vital component of
      family-integrated care in the NICU.

PMID- 23532032
TI  - Treatment of intraventricular hemorrhages in premature infants: where is the
      evidence?

PMID- 23532033
TI  - Comparison of lipid and calorie loss from donor human milk among 3 methods of
      simulated gavage feeding: one-hour, 2-hour, and intermittent gravity feedings.
AB  - PURPOSE: The objective of this study was to compare the differences in lipid loss
      from 24 samples of banked donor human milk (DHM) among 3 feeding methods: DHM
      given by syringe pump over 1 hour, 2 hours, and by bolus/gravity gavage. DESIGN:
      Comparative, descriptive. There were no human subjects. METHODS: Twenty-four
      samples of 8 oz of DHM were divided into four 60-mL aliquots. Timed feedings were
      given by Medfusion 2001 syringe pumps with syringes connected to narrow-lumened
      extension sets designed for enteral feedings and connected to standard silastic
      enteral feeding tubes. Gravity feedings were given using the identical syringes
      connected to the same silastic feeding tubes. All aliquots were analyzed with the
      York Dairy Analyzer. Univariate repeated-measures analyses of variance were used
      for the omnibus testing for overall differences between the feeding methods.
      Lipid content expressed as grams per deciliter at the end of each feeding method
      was compared with the prefed control samples using the Dunnett's test. The Tukey
      correction was used for other pairwise multiple comparisons. RESULTS: The
      univariate repeated-measures analysis of variance conducted to test for overall
      differences between feeding methods showed a significant difference between the
      methods (F = 58.57, df = 3, 69, P < .0001). Post hoc analysis using the Dunnett's
      approach revealed that there was a significant difference in fat content between
      the control sample and the 1-hour and 2-hours feeding methods (P < .0001), but we
      did not find any significant difference in fat content between the control and
      the gravity feeding methods (P = .3296). Pairwise comparison using the Tukey
      correction revealed a significant difference between both gravity and 1-hour
      feeding methods (P < .0001), and gravity and 2-hour feeding method (P < .0001).
      There was no significant difference in lipid content between the 1-hour and 2
      hour feeding methods (P = .2729). CONCLUSIONS: Unlike gravity feedings, the timed
      feedings resulted in a statistically significant loss of fat as compared with
      their controls. These findings should raise questions about how those infants in
      the neonatal intensive care unit are routinely gavage fed.

PMID- 23532034
TI  - The toxigen initiative: targeting oxygen saturation to avoid sequelae in very
      preterm infants.
AB  - Supplemental oxygen plays a critical role in the care of infants born at the
      lower limits of viability, but not without the risk of morbidity resulting from
      high levels or prolonged exposure. PURPOSE: The purpose of this quality
      improvement project was to reduce exposure to hyperoxia as evidenced by SpO2
      values within the established target range (88%-92%) among very preterm infants
      (VPIs) in a level 3 neonatal intensive care unit (NICU). Reducing exposure to
      hyperoxia in this population of exquisitely vulnerable infants has been
      associated with reduced morbidity, including retinopathy of prematurity, chronic
      lung disease, and brain injury. SUBJECTS: Two populations of interest were
      identified: VPIs receiving supplemental oxygen and NICU clinicians. DESIGN:
      Interventions were employed to (1) improve knowledge regarding hyperoxia and
      associated outcome sequelae in an interdisciplinary sample of clinicians (pretest
      posttest design) and (2) reinforce content of the educational intervention by
      triggering caregiver behaviors to reduce time the VPIs is above target SpO2 range
      while receiving supplemental oxygen (cohort design). METHODS: : Retrospective
      chart review, baseline clinician knowledge assessment, education, posteducation
      assessment, collaborative rounds with regular feedback citing time VPIs spent
      above target oxygen saturation levels (SpO2), and evaluation of impact on time
      infants spent above target SpO2 range aligned with the project purpose. OUTCOME
      MEASURES: Pre- and postintervention dependent variables included clinician
      knowledge of hyperoxia and related evidence as measured by a 24-item multiple
      choice Knowledge Assessment Tool before and after attending an educational
      presentation. Time VPIs were exposed to hyperoxia was evaluated using SpO2
      readings and calculating the percentage of time readings were above target range
      before and after the introduction of educational and behavioral interventions.
      PRINCIPAL RESULTS: Outcome 1 was to increase knowledge about hyperoxia among
      clinician caregivers. Paired-samples t test showed a significant difference
      between preintervention and postintervention Knowledge Assessment Tool scores (P
      = .000). Outcome 2 measured reduction in time spent with SpO2 readings above
      target range. An independent-samples t test was used to compare outcomes in
      preintervention and postintervention VPI cohorts. Mean time spent with SpO2
      greater than target range increased in the postintervention cohort, reaching
      statistical significance with P = .047. CONCLUSIONS: Knowledge acquisition on the
      subject of hyperoxia in VPIs was achieved. Decreasing the percent time VPIs were
      exposed to hyperoxia was not attained. The postintervention VPI cohort spent more
      time above the target saturation range despite greater knowledge among
      clinicians.

PMID- 23532035
TI  - Nasal continuous positive airway pressure: a multisite study of suctioning
      practices within NICUs.
AB  - PURPOSE: The purpose of this multisite study was to describe suctioning
      techniques of registered nurses (RNs) and respiratory therapists (RTs) caring for
      neonates requiring nasal continuous positive airway pressure (CPAP). The care
      practices investigated included suctioning frequency, assessment parameters, and
      techniques used to suction. SUBJECTS: A convenience sample of neonatal intensive
      care unit (NICU) RNs and practicing RTs at 8 Midwestern hospitals in the United
      States caring for neonates on nasal CPAP in a level II or III NICU were included.
      Eighty-five percent of respondents were RNs of which almost 89% (88.6%) were
      staff RNs, 63% were bachelor prepared, and 33% of the RNs had greater than 20
      years of neonatal nursing experience. DESIGN: A cross-sectional descriptive
      comparative design was used for this study. METHODS: An investigator-developed
      Web-based survey pertaining to current practice concerns was developed by the
      research team. The 31-item survey tool consisted of 4 sections. The first section
      addressed the frequency of suctioning. The second section addressed assessment
      parameters used to determine the need for suctioning. The third section addressed
      the technique used to suction, including gloving techniques, hyperoxygenation,
      and the use of catheters in nares and mouth and suctioning devices. Demographic
      data, including staff position, level of education, years of nursing, and NICU
      experience and certification, were collected in the fourth section. Descriptive
      statistics were used to characterize demographics and each item of the survey.
      Chi-square statistics (Pearson chi-square and Fisher Exact text) were used to
      compare RNs' and RTs' nasal CPAP suctioning practices. PRINCIPAL RESULTS: The
      results of this study indicated that decision making related to the need to
      suction was variable. In addition, the frequency of suctioning and nasopharyngeal
      and oropharyngeal suctioning techniques were highly variable for neonates
      requiring nasal CPAP. CONCLUSIONS: Despite the treatment of respiratory distress
      with nasal CPAP, there are no best practice guidelines for providing
      nasopharyngeal and oropharyngeal suctioning for maintenance of a patent airway.
      Future randomized controlled clinical trials are needed to develop best practices
      for nasal CPAP suctioning.

PMID- 23532036
TI  - Pitfalls in Autier and Boniol's estimate of self-selection in case-control
      studies.

PMID- 23532037
TI  - Bio-based hyperbranched polyurethane/Fe3O4 nanocomposites: smart antibacterial
      biomaterials for biomedical devices and implants.
AB  - The fabrication of a smart magnetically controllable bio-based polymeric
      nanocomposite (NC) has immense potential in the biomedical domain. In this
      context, magneto-thermoresponsive sunflower oil modified hyperbranched
      polyurethane (HBPU)/Fe3O4 NCs with different wt.% of magnetic nanoparticles
      (Fe3O4) were prepared by an in situ polymerization technique. Fourier-transform
      infrared, x-ray diffraction, vibrating sample magnetometer, scanning electron
      microscope, transmission electron microscope, thermal analysis and differential
      scanning calorimetric were used to analyze various physico-chemical structural
      attributes of the prepared NC. The results showed good interfacial interactions
      between HBPU and well-dispersed superparamagnetic Fe3O4, with an average diameter
      of 7.65 nm. The incorporation of Fe3O4 in HBPU significantly improved the thermo
      mechanical properties along with the shape-memory behavior, antibacterial
      activity, biocompatibility as well as biodegradability in comparison to the
      pristine system. The cytocompatibility of the degraded products of the NC was
      also verified by in vitro hemolytic activity and MTT assay. In addition, the in
      vivo biocompatibility and non-immunological behavior, as tested in Wistar rats
      after subcutaneous implantation, show promising signs for the NC to be used as
      antibacterial biomaterial for biomedical device and implant applications.

PMID- 23532038
TI  - The changing seasonal climate in the Arctic.
AB  - Ongoing and projected greenhouse warming clearly manifests itself in the Arctic
      regions, which warm faster than any other part of the world. One of the key
      features of amplified Arctic warming concerns Arctic winter warming (AWW), which
      exceeds summer warming by at least a factor of 4. Here we use observation-driven
      reanalyses and state-of-the-art climate models in a variety of standardised
      climate change simulations to show that AWW is strongly linked to winter sea ice
      retreat through the associated release of surplus ocean heat gained in summer
      through the ice-albedo feedback (~25%), and to infrared radiation feedbacks
      (~75%). Arctic summer warming is surprisingly modest, even after summer sea ice
      has completely disappeared. Quantifying the seasonally varying changes in Arctic
      temperature and sea ice and the associated feedbacks helps to more accurately
      quantify the likelihood of Arctic's climate changes, and to assess their impact
      on local ecosystems and socio-economic activities.

PMID- 23532039
TI  - [Microenvironment and colorectal liver metastases angiogenesis: surgical
      implications].
AB  - Stephen Paget's proposed an original "seed and soil" theory, with organ
      preference patterns of tumor metastasis resulting in interaction between
      metastatic tumor cells and their specific microenvironment. There is many
      experimental and clinical data showing that this theory is validated. More
      recently, it has been suggested that early changes in the microenvironment at the
      distant sites, could be induced by the primary tumor, reported as "pre-metastatic
      niche" formation. Tumor cells could produce growth factors, cytokines which could
      facilitate the recruitment and the mobilization of the bone marrow-derived
      endothelial progenitor cells, and thus necessary for the tumor neovascularization
      and metastasis growth. Although the clinical value of the concept of the
      premetastatic niche is not yet elucidated, these data could encourage surgeons to
      perform the colorectal surgery first and then the liver surgery, in patients with
      synchronous colorectal liver metastases. The reciprocal interactions between
      primary tumor and microenvironment at the distant sites are therefore determinant
      for tumor progression. Taken together, the microenvironment is an important
      therapeutic target and surgeons and oncologist could discuss the choice of
      different surgical strategy for patient with synchronous colorectal liver
      metastases regarding the interaction with the microenvironment affected by
      primary tumor resection.

PMID- 23532040
TI  - Evaluation of developmental responses of two crop plants exposed to silver and
      zinc oxide nanoparticles.
AB  - The increasing applications of different nanomaterials in the myriad of nano
      enabled products and their potential for leaching have raised considerable
      environmental, health and safety (EHS) concerns. As systematic studies
      investigating potential anomalies in the morphology and anatomy of crop plants
      are scarce, herein we report on the developmental responses of two agriculturally
      significant crop plants, maize (Zea mays L.) and cabbage (Brassica oleracea var.
      capitata L.), upon in vitro exposure to nanoparticles of citrate-coated silver
      (Citrate-nAg) and zinc oxide (nZnO). Analyses involve histology of the primary
      root morphology and anatomy using light microscopy, metal biouptake, moisture
      content, rate of germination, and root elongation. Comparative toxicity profiles
      of the ionic salts (AgNO3 and ZnSO4) are developed. Notably, we uncover
      structural changes in maize primary root cells upon exposure to Citrate-nAg,
      nZnO, AgNO3, and ZnSO4, possibly due to metal biouptake, suggesting potential for
      functional impairments in the plant growth and development. Citrate-nAg exposure
      results in lower Ag biouptake compared to AgNO3 treatment in maize. Microscopic
      evidence reveals 'tunneling-like effect' with nZnO treatment, while exposure to
      AgNO3 leads to cell erosion in maize root apical meristem. In maize, a
      significant change in metaxylem count is evident with Citrate-nAg, AgNO3, and
      ZnSO4 treatment, but not with nZnO treatment (p>0.1). In both maize and cabbage,
      measures of germination and root elongation reveal lower nanoparticle toxicity
      compared to free ions. As moisture data do not support osmotically-induced water
      stress hypothesis for explaining toxicity, we discuss other proximate mechanisms
      including the potential role of growth hormones and transcription factors. These
      findings highlight previously overlooked, anatomically significant effects of
      metal nanoparticles, and recommend considering detailed anatomical investigations
      in tandem with the standard developmental phytotoxicity assays (germination and
      root elongation) as the latter ones appear less sensitive for screening plant
      responses to nanomaterial insults.

PMID- 23532041
TI  - Characterization of groundwater resources in the Trinity and Woodbine aquifers in
      Texas.
AB  - A vast region in north-central Texas, centering on Dallas-Fort Worth metroplex,
      suffers from intense groundwater drawdown and water quality degradation, which
      led to inclusion of 18 counties of this region into Priority Groundwater
      Management Areas. We combined aquifer-based and county-based hydrologic analyses
      to (1) assess spatio-temporal changes in groundwater level and quality between
      1960 and 2010 in the Trinity and Woodbine aquifers underlying the study region,
      (2) delve into major hydrochemical facies with reference to aquifer
      hydrostratigraphy, and (3) identify county-based spatial zones to aid in future
      groundwater management initiatives. Water-level and quality data was obtained
      from the Texas Water Development Board (TWDB) and analyzed on a decadal scale.
      Progressive water-level decline was the major concern in the Trinity aquifer with
      >50% of observations occurring at depths >100 m since the 1980s, an observation
      becoming apparent only in the 2000s in the Woodbine aquifer. Water quality
      degradation was the major issue in the Woodbine aquifer with substantially higher
      percentage of observations exceeding the secondary maximum contaminant levels
      (SMCL; a non-enforceable threshold set by the United State Environmental
      Protection Agency (USEPA)) and/or maximum contaminant level (MCL, a legally
      enforceable drinking water standard set by the USEPA) for sulfate (SO4(2-)),
      chloride (Cl(-)), and fluoride (F(-)) in each decade. In both aquifers, however,
      >70% of observations exceeded the SMCL for total dissolved solids indicating high
      groundwater salinization. Water-level changes in Trinity aquifer also had
      significant negative impact on water quality. Hydrochemical facies in this region
      sequentially evolved from Ca-Mg-HCO3 and Ca-HCO3 in the fluvial sediments of the
      west to Na-SO4-Cl in the deltaic sediments to the east. Sequentially evolving
      hydrogeochemical facies and increasing salinization closely resembled regional
      groundwater flow pattern. Distinct spatial zones based on homogenous hydrologic
      characteristics have become increasingly apparent over time indicating necessity
      of zone-specific groundwater management strategies.

PMID- 23532042
TI  - Arabidopsis thaliana root elongation growth is sensitive to lunisolar tidal
      acceleration and may also be weakly correlated with geomagnetic variations.
AB  - BACKGROUND: Correlative evidence suggests a relationship between the lunisolar
      tidal acceleration and the elongation rate of arabidopsis roots grown under free
      running conditions of constant low light. METHODS: Seedlings of Arabidopsis
      thaliana were grown in a controlled-climate chamber maintained at a constant
      temperature and subjected to continuous low-level illumination from fluorescent
      tubes, conditions that approximate to a 'free-running' state in which most of the
      abiotic factors that entrain root growth rates are excluded. Elongation of evenly
      spaced, vertical primary roots was recorded continuously over periods of up to 14
      d using high temporal- and spatial-resolution video imaging and were analysed in
      conjunction with geophysical variables. KEY RESULTS AND CONCLUSIONS: The results
      confirm the lunisolar tidal/root elongation relationship. Also presented are
      relationships between the hourly elongation rates and the contemporaneous
      variations in geomagnetic activity, as evaluated from the disturbance storm time
      and ap indices. On the basis of time series of root elongation rates that extend
      over >=4 d and recorded at different seasons of the year, a provisional
      conclusion is that root elongation responds to variation in the lunisolar force
      and also appears to adjust in accordance with variations in the geomagnetic
      field. Thus, both lunisolar tidal acceleration and the geomagnetic field should
      be considered as modulators of root growth rate, alongside other, stronger and
      more well-known abiotic environmental regulators, and perhaps unexplored factors
      such as air ions. Major changes in atmospheric pressure are not considered to be
      a factor contributing to oscillations of root elongation rate.

PMID- 23532043
TI  - Variation in nutrient-acquisition patterns by mycorrhizal fungi of rare and
      common orchids explains diversification in a global biodiversity hotspot.
AB  - BACKGROUND AND AIMS: Many terrestrial orchids have an obligate requirement for
      mycorrhizal associations to provide nutritional support from germination to
      establishment. This study will investigate the ability of orchid mycorrhizal
      fungi (OMF) to utilize a variety of nutrient sources in the nutrient-impoverished
      (low organic) soils of the Southwest Australian Floristic Region (SWAFR) in order
      to effectively compete, survive and sustain the orchid host. METHODS: Mycorrhizal
      fungi representing key OMF genera were isolated from three common and widespread
      species: Pterostylis recurva, Caladenia flava and Diuris corymbosa, and one rare
      and restricted species: Drakaea elastica. The accessibility of specific nutrients
      was assessed by comparing growth including dry biomass of OMF in vitro on basal
      CN MMN liquid media. KEY RESULTS: Each of the OMF accessed and effectively
      utilized a wide variety of nutrient compounds, including carbon (C) sources,
      inorganic and organic nitrogen (N) and inorganic and organic phosphorus (P). The
      nutrient compounds utilized varied between the genera of OMF, most notably
      sources of N. CONCLUSIONS: These results suggest that OMF can differentiate
      between niches (micro-niche specialization) in a constrained, highly resource
      limited environment such as the SWAFR. Phosphorus is the most limited
      macronutrient in SWAFR soils and the ability to access phytate by OMF indicates a
      characterizing functional capacity of OMF from the SWAFR. Furthermore, compared
      with OMF isolated from the rare D. elastica, OMF associating with the common P.
      recurva produced far greater biomass over a wider variety of nutritional sources.
      This suggests a broader tolerance for habitat variation providing more
      opportunities for the common orchid for recruitment and establishment at a site.

PMID- 23532044
TI  - DNA profiling, telomere analysis and antioxidant properties as tools for
      monitoring ex situ seed longevity.
AB  - BACKGROUND AND AIMS: The germination test currently represents the most used
      method to assess seed viability in germplasm banks, despite the difficulties
      caused by the occurrence of seed dormancy. Furthermore, seed longevity can vary
      considerably across species and populations from different environments, and
      studies related to the eco-physiological processes underlying such variations are
      still limited in their depth. The aim of the present work was the identification
      of reliable molecular markers that might help in monitoring seed deterioration.
      METHODS: Dry seeds were subjected to artificial ageing and collected at different
      time points for molecular/biochemical analyses. DNA damage was measured using the
      RAPD (random amplified polymorphic DNA) approach while the seed antioxidant
      profile was obtained using both the DPPH (1,1-diphenyl, 2-picrylhydrazyl) assay
      and the Folin-Ciocalteu reagent method. Electron paramagnetic resonance (EPR)
      provided profiles of free radicals. Quantitative real-time polymerase chain
      reaction (QRT-PCR) was used to assess the expression profiles of the antioxidant
      genes MT2 (type 2 metallothionein) and SOD (superoxide dismutase). A modified QRT
      PCR protocol was used to determine telomere length. KEY RESULTS: The RAPD
      profiles highlighted different capacities of the two Silene species to overcome
      DNA damage induced by artificial ageing. The antioxidant profiles of dry and
      rehydrated seeds revealed that the high-altitude taxon Silene acaulis was
      characterized by a lower antioxidant specific activity. Significant upregulation
      of the MT2 and SOD genes was observed only in the rehydrated seeds of the low
      altitude species. Rehydration resulted in telomere lengthening in both Silene
      species. CONCLUSIONS: Different seed viability markers have been selected for
      plant species showing inherent variation of seed longevity. RAPD analysis,
      quantification of redox activity of non-enzymatic antioxidant compounds and gene
      expression profiling provide deeper insights to study seed viability during
      storage. Telomere lengthening is a promising tool to discriminate between short-
      and long-lived species.

PMID- 23532045
TI  - Mycorrhizas alter nitrogen acquisition by the terrestrial orchid Cymbidium
      goeringii.
AB  - BACKGROUND AND AIMS: Orchid mycorrhizas exhibit a unique type of mycorrhizal
      symbiosis that occurs between fungi and plants of the family Orchidaceae. In
      general, the roots of orchids are typically coarse compared with those of other
      plant species, leading to a considerably low surface area to volume ratio. As a
      result, orchids are often ill-adapted for direct nutrient acquisition from the
      soil and so mycorrhizal associations are important. However, the role of the
      fungal partners in the acquisition of inorganic and organic N by terrestrial
      orchids has yet to be clarified. METHODS: Inorganic and amino acid N uptake by
      non-mycorrhizal and mycorrhizal Cymbidium goeringii seedlings, which were grown
      in pots in a greenhouse, was investigated using a (15)N-labelling technique in
      which the tracer was injected at two different soil depths, 2.5 cm or 7.5 cm.
      Mycorrhizal C. goeringii seedlings were obtained by inoculation with three
      different mycorrhizal strains isolated from the roots of wild terrestrial orchids
      (two C. goeringii and one C. sinense). KEY RESULTS: Non-mycorrhizal C. goeringii
      primarily took up NO3(-) from tracers injected at 2.5-cm soil depth, whereas C.
      goeringii inoculated with all three mycorrhiza primarily took up NH4(+) injected
      at the same depth. Inoculation of the mycorrhizal strain MLX102 (isolated from
      adult C. sinense) on C. goeringii roots only significantly increased the below
      ground biomass of the C. goeringii; however, it enhanced (15)NH4(+) uptake by C.
      goeringii at 2.5-cm soil depth. Compared to the uptake of tracers injected at 2.5
      cm soil depth, the MLX102 fungal strain strongly enhanced glycine-N uptake by C.
      goeringii from tracers injected at 7.5-cm soil depth. Cymbidium goeringii
      inoculated with CLB113 and MLX102 fungal strains demonstrated a similar N uptake
      pattern to tracers injected at 2.5-cm soil depth. CONCLUSIONS: These findings
      demonstrate that mycorrhizal fungi are able to switch the primary N source uptake
      of a terrestrial orchid, in this case C. goeringii, from NO3(-) to NH4(+). The
      reasons for variation in N uptake in the different soil layers may be due to
      possible differentiation in the mycorrhizal hyphae of the C. goeringii fungal
      partner.

PMID- 23532046
TI  - Evolution of cryptic gene pools in Hypericum perforatum: the influence of
      reproductive system and gene flow.
AB  - BACKGROUND AND AIMS: Hypericum perforatum (St. John's wort) is a widespread
      Eurasian perennial plant species with remarkable variation in its morphology,
      ploidy and breeding system, which ranges from sex to apomixis. Here, hypotheses
      on the evolutionary origin of St. John's wort are tested and contrasted with the
      subsequent history of interspecific gene flow. METHODS: Extensive field
      collections were analysed for quantitative morphological variation, ploidy,
      chromosome numbers and genetic diversity using nuclear (amplified fragment length
      polymorphism) and plastid (trnL-trnF) markers. The mode of reproduction was
      analysed by FCSS (flow cytometric seed screen). KEY RESULTS: It is demonstrated
      that H. perforatum is not of hybrid origin, and for the first time wild diploid
      populations are documented. Pseudogamous facultative apomictic reproduction is
      prevalent in the polyploids, whereas diploids are predominantly sexual, a
      phenomenon which also characterizes its sister species H. maculatum. Both
      molecular markers characterize identical major gene pools, distinguishing H.
      perforatum from H. maculatum and two genetic groups in H. perforatum. All three
      gene pools are in close geographical contact. Extensive gene flow and
      hybridization throughout Europe within and between gene pools and species is
      exemplified by the molecular data and confirmed by morphometric analyses.
      CONCLUSIONS: Hypericum perforatum is of a single evolutionary origin and later
      split into two major gene pools. Subsequently, independent and recurrent
      polyploidization occurred in all lineages and was accompanied by substantial gene
      flow within and between H. perforatum and H. maculatum. These processes are
      highly influenced by the reproductive system in both species, with a switch to
      predominantly apomictic reproduction in polyploids, irrespective of their origin.

PMID- 23532047
TI  - Leaf life span spectrum of tropical woody seedlings: effects of light and
      ontogeny and consequences for survival.
AB  - BACKGROUND AND AIMS: Leaf life span is widely recognized as a key life history
      trait associated with herbivory resistance, but rigorous comparative data are
      rare for seedlings. The goal of this study was to examine how light environment
      affects leaf life span, and how ontogenetic development during the first year may
      influence leaf fracture toughness, lamina density and stem density that are
      relevant for herbivory resistance, leaf life span and seedling survival. METHODS:
      Data from three experiments encompassing 104 neotropical woody species were
      combined. Leaf life span, lamina and vein fracture toughness, leaf and stem
      tissue density and seedling survival were quantified for the first-year seedlings
      at standardized ontogenetic stages in shade houses and common gardens established
      in gaps and shaded understorey in a moist tropical forest in Panama. Mortality of
      naturally recruited seedlings till 1 year later was quantified in 800 1-m2 plots
      from 1994 to 2011. KEY RESULTS: Median leaf life span ranged widely among
      species, always greater in shade (ranging from 151 to >1790 d in the understorey
      and shade houses) than in gaps (115-867 d), but with strong correlation between
      gaps and shade. Leaf and stem tissue density increased with seedling age, whereas
      leaf fracture toughness showed only a weak increase. All these traits were
      positively correlated with leaf life span. Leaf life span and stem density were
      negatively correlated with seedling mortality in shade, while gap mortality
      showed no correlation with these traits. CONCLUSIONS: The wide spectrum of leaf
      life span and associated functional traits reflects variation in shade tolerance
      of first-year seedlings among coexisting trees, shrubs and lianas in this
      neotropical forest. High leaf tissue density is important in enhancing leaf
      toughness, a known physical defence, and leaf life span. Both seedling leaf life
      span and stem density should be considered as key functional traits that
      contribute to seedling survival in tropical forest understoreys.

PMID- 23532048
TI  - Quantitative imaging of rhizosphere pH and CO2 dynamics with planar optodes.
AB  - BACKGROUND AND AIMS: Live imaging methods have become extremely important for the
      exploration of biological processes. In particular, non-invasive measurement
      techniques are key to unravelling organism-environment interactions in close-to
      natural set-ups, e.g. in the highly heterogeneous and difficult-to-probe
      environment of plant roots: the rhizosphere. pH and CO2 concentration are the
      main drivers of rhizosphere processes. Being able to monitor these parameters at
      high spatio-temporal resolution is of utmost importance for relevant
      interpretation of the underlying processes, especially in the complex environment
      of non-sterile plant-soil systems. This study introduces the application of easy
      to-use planar optode systems in different set-ups to quantify plant root-soil
      interactions. METHODS: pH- and recently developed CO2-sensors were applied to
      rhizobox systems to investigate roots with different functional traits,
      highlighting the potential of these tools. Continuous and highly resolved real
      time measurements were made of the pH dynamics around Triticum turgidum durum
      (durum wheat) roots, Cicer arietinum (chickpea) roots and nodules, and CO2
      dynamics in the rhizosphere of Viminaria juncea. KEY RESULTS: Wheat root tips
      acidified slightly, while their root hair zone alkalized their rhizosphere by
      more than 1 pH unit and the effect of irrigation on soil pH could be visualized
      as well. Chickpea roots and nodules acidified the surrounding soil during N2
      fixation and showed diurnal changes in acidification activity. A growing root of
      V. juncea exhibited a large zone of influence (mm) on soil CO2 content and
      therefore on its biogeochemical surrounding, all contributing to the extreme
      complexity of the root-soil interactions. CONCLUSIONS: This technique provides a
      unique tool for future root research applications and overcomes limitations of
      previous systems by creating quantitative maps without, for example,
      interpolation and time delays between single data points.

PMID- 23532049
TI  - Complete tylosis formation in a latest Permian conifer stem.
AB  - BACKGROUND AND AIMS: Our knowledge of tylosis formation is mainly based on
      observations of extant plants; however, its developmental and functional
      significance are less well understood in fossil plants. This study, for the first
      time, describes a complete tylosis formation in a fossil woody conifer and
      discusses its ecophysiological implications. METHODS: The permineralized stem of
      Shenoxylon mirabile was collected from the upper Permian (Changhsingian)
      Sunjiagou Formation of Shitanjing coalfield, northern China. Samples from
      different portions of the stem were prepared by using the standard thin
      sectioning technique and studied in transmitted light. KEY RESULTS: The outgrowth
      of ray parenchyma cells protruded into adjacent tracheids through pits initially
      forming small pyriform or balloon-shaped structures, which became globular or
      slightly elongated when they reached their maximum size. The tracheid luminae
      were gradually occluded by densely spaced tyloses. The host tracheids are
      arranged in distinct concentric zones representing different growth phases of
      tylosis formation within a single growth ring. CONCLUSIONS: The extensive
      development of tyloses from the innermost heartwood (metaxylem) tracheids to the
      outermost sapwood tracheids suggests that the plant was highly vulnerable and
      reacted strongly to environmental stress. Based on the evidence available, the
      tyloses were probably not produced in response to wound reaction or pathogenic
      infection, since evidence of wood traumatic events or fungal invasion are not
      recognizable. Rather, they may represent an ecophysiological response to the
      constant environmental stimuli.

PMID- 23532050
TI  - Measurements of single molecular affinity interactions between carbohydrate
      binding modules and crystalline cellulose fibrils.
AB  - Combining atomic force microscopy (AFM) recognition imaging and single molecule
      dynamic force spectroscopy (SMDFS), we studied the single molecule affinity
      interactions between the carbohydrate-binding module (CBM) and plant cell wall
      cellulose using the CBM3a (from Clostridium thermocellum) and CBM2a (from
      Cellvibrio japonicus) functionalized AFM tips. The binding efficiencies of the
      CBMs to the cellulose were determined by the binding areas on the crystalline
      cellulose fibrils surface using the recognition imaging. Several dynamic and
      kinetic parameters, such as the reconstructed free energy change, energy barrier
      and bond lifetime constant, were also obtained based on the measured single
      molecule unbinding forces, which are used to illuminate the affinity of the CBMs
      binding to the natural and single cellulose surface from a totally different
      aspect. It was found that CBM3a has a little higher binding efficiency and
      affinity than CBM2a to both natural and extracted cellulose surfaces and both the
      CBMs have higher affinities to the natural cell wall cellulose compared to the
      extracted single cellulose. The in-depth understanding of the binding mechanisms
      of the CBM-cellulose interactions of this study may pave the way for more
      efficient plant cell wall degradation and eventually facilitate biofuel
      production.

PMID- 23532051
TI  - Sodium cubane and double-cubane aggregates of hybridised salicylaldimines and
      their transmetallation to nickel for catalytic ethylene oligomerisation.
AB  - Deprotonation of functional salicylaldimines with NaH invariably results in
      cubane or double-cubane Na(I) aggregates which transmetallate with Ni(II) under
      different stoichiometric conditions to give Ni(II) complexes that are
      catalytically active towards ethylene oligomerisation.

PMID- 23532052
TI  - Polygenic heritability estimates in pharmacogenetics: focus on asthma and related
      phenotypes.
AB  - Although accurate measures of heritability are required to understand the
      pharmacogenetic basis of drug treatment response, these are generally not
      available, as it is unfeasible to give medications to individuals for which
      treatment is not indicated. Using a polygenic linear mixed modeling approach, we
      estimated lower bounds on the heritability of asthma and the heritability of two
      related drug-response phenotypes, bronchodilator response and airway
      hyperreactivity, using genome-wide single nucleotide polymorphism (SNP) data from
      existing asthma cohorts. Our estimate of the heritability for bronchodilator
      response is 28.5% (SE 16%, P=0.043) and airway hyperresponsiveness is 51.1% (SE
      34%, P=0.064), whereas we estimate asthma genetic liability at 61.5% (SE 16%,
      P<0.001). Our results agree with the previously published estimates of the
      heritability of these traits, suggesting that the linear mixed modeling method is
      useful for computing the heritability of other pharmacogenetic traits.
      Furthermore, our results indicate that multiple SNP main effects, including SNPs
      as yet unidentified by genome-wide association study methods, together explain a
      sizable portion of the heritability of these traits.

PMID- 23532053
TI  - Matching by propensity score in cohort studies with three treatment groups.
AB  - BACKGROUND: Nonrandomized pharmacoepidemiology generally compares one medication
      with another. For many conditions, clinicians can benefit from comparing the
      safety and effectiveness of three or more appropriate treatment options. We
      sought to compare three treatment groups simultaneously by creating 1:1:1
      propensity score-matched cohorts. METHODS: We developed a technique that
      estimates generalized propensity scores and then creates 1:1:1 matched sets. We
      compared this methodology with two existing approaches-construction of matched
      cohorts through a common-referent group and a pairwise match for each possible
      contrast. In a simulation, we varied unmeasured confounding, presence of
      treatment effect heterogeneity, and the prevalence of treatments and compared
      each method's bias, variance, and mean squared error (MSE) of the treatment
      effect. We applied these techniques to a cohort of rheumatoid arthritis patients
      treated with nonselective nonsteroidal anti-inflammatory drugs, COX-2 selective
      inhibitors, or opioids. RESULTS: We performed 1000 simulation runs. In the base
      case, we observed an average bias of 0.4% (MSE * 100 = 0.2) in the three-way
      matching approach and an average bias of 0.3% (MSE * 100 = 0.2) with the pairwise
      technique. The techniques showed differing bias and MSE with increasing treatment
      effect heterogeneity and decreasing propensity score overlap. With highly unequal
      exposure prevalences, strong heterogeneity, and low overlap, we observed a bias
      of 6.5% (MSE * 100 = 10.8) in the three-way approach and 12.5% (MSE * 100 = 12.3)
      in the pairwise approach. The empirical study displayed better covariate balance
      using the pairwise approach. Point estimates were substantially similar.
      CONCLUSIONS: Our matching approach offers an effective way to study the safety
      and effectiveness of three treatment options. We recommend its use over the
      pairwise or common-referent approaches.

PMID- 23532054
TI  - COX-2 selective nonsteroidal anti-inflammatory drugs and risk of gastrointestinal
      tract complications and myocardial infarction: an instrumental variable analysis.
AB  - OBJECTIVE: Instrumental variable analysis can estimate treatment effects in the
      presence of residual or unmeasured confounding. We compared ordinary least
      squares regression versus instrumental variable estimates of the effects of
      selective cyclooxygenase-2 inhibitors (COX-2s) relative to nonselective
      nonsteroidal anti-inflammatory drug (NSAID) prescriptions on incidence of upper
      gastrointestinal complications and myocardial infarction (MI). METHODS: We
      sampled a cohort of 62,933 first-time users of COX-2s or nonselective NSAIDs
      older than 60 years in the Clinical Practice Research Datalink. The instruments
      were physicians' previous prescriptions of COX-2s or nonselective NSAIDs, which
      are surrogates for physician preferences. We estimated risk differences of
      incident upper gastrointestinal complications and MI within 180 days of first COX
      2 versus nonselective NSAID prescription. RESULTS: Using ordinary least squares
      regression, adjusted for baseline confounders, we observed little association of
      COX-2 prescriptions with incident upper gastrointestinal complications (risk
      difference = -0.08 [95% confidence interval = -0.20 to 0.04]) or MI (0.06 [-0.06
      to 0.17]) per 100 patients treated. Our adjusted instrumental variable results
      suggested 0.46 per 100 (-0.15 to 1.07) fewer upper gastrointestinal complications
      and little difference in acute MIs (0.08 per 100 [-0.61 to 0.76]), within 180
      days of being prescribed COX-2s. Estimates were more precise when we used 20
      previous prescriptions; the instrumental variable analysis implied 0.74 (0.28 to
      1.19) fewer MIs per 100 patients prescribed COX-2s. CONCLUSIONS: Using
      instrumental variable analysis, we found some evidence that COX-2 prescriptions
      reduced the risk of upper gastrointestinal complications, consistent with
      randomized controlled trials. Our results using multiple instruments suggest that
      COX-2s may have heterogeneous within-class effects on MI.

PMID- 23532055
TI  - Issues in the reporting and conduct of instrumental variable studies: a
      systematic review.
AB  - Instrumental variables can be used to estimate the causal effects of exposures on
      outcomes in the presence of residual or uncontrolled confounding. To assess the
      validity of analyses using instrumental variables, specific information about
      whether underlying assumptions are met must be presented, in particular to
      demonstrate that the instrument is associated with the exposure but not with
      measured confounding factors. We systematically reviewed the epidemiological
      literature in Embase and Medline for articles containing the term "instrumental
      variable$" to investigate whether reporting of test statistics in studies using
      instrumental variables was sufficient to assess the validity of the results. We
      extracted the information each study reported about their instrumental variables,
      including specification tests used to check assumptions. The search found 756
      studies of which 90 were relevant and were included. Only 25 (28%) studies
      reported appropriate tests of the strength of the associations between
      instruments and exposure. Forty-four (49%) studies reported associations between
      the instrumental variables and observed covariates. Studies using instrumental
      variables had wide confidence intervals and so effect estimates were imprecise.
      We propose a checklist of information and specification tests that studies using
      instrumental variables should report.

PMID- 23532057
TI  - A pyrrolidinium nitrate protic ionic liquid-based electrolyte for very low
      temperature electrical double-layer capacitors.
AB  - This study describes the use of the pyrrolidinium nitrate ([Pyrr][NO3]) protic
      ionic liquid (PIL) in a mixture with gamma butyrolactone (gamma-BL) as an
      electrolyte for carbon-based supercapacitors with an operating voltage of 2.0 V
      and at very low temperature. Thermal and transport properties of this electrolyte
      were firstly evaluated from -40  degrees C to 80  degrees C. The evolution of
      conductivity with the addition of gamma-BL rendered it possible to determine the
      optimal composition for electrochemical application, with a molar fraction of
      gamma-BL of 0.6. This mixture shows a Newtonian behavior with a low viscosity
      value of 5 mPa s at 25  degrees C, and exhibits high conductivity values of up to
      65 mS cm(-1) at 80  degrees C. At the same time, exceptional residual
      conductivity was measured for this composition at -40  degrees C (9 mS cm(-1)),
      thanks to the superionic character of pyrrolidinium nitrate PIL. Electrochemical
      characterization of this electrolyte demonstrated, at first, a passivation on the
      aluminum collector, secondly good cycling performances with an activated carbon
      electrode from 50  degrees C to -40  degrees C with capacitance up to 132 F g(-1)
      at room temperature and a wide voltage window (2.0 V). Finally at very low
      temperature (-40  degrees C), this system demonstrates an unprecedented
      combination of high specific capacitance (up to 117 F g(-1)), and rapid charging
      discharging even at high current density, which is very promising for the
      progress of energy storage systems with environmentally friendly electrolytes at
      such very low temperatures.

PMID- 23532056
TI  - Imaging the action of antimicrobial peptides on living bacterial cells.
AB  - Antimicrobial peptides hold promise as broad-spectrum alternatives to
      conventional antibiotics. The mechanism of action of this class of peptide is a
      topical area of research focused predominantly on their interaction with
      artificial membranes. Here we compare the interaction mechanism of a model
      antimicrobial peptide with single artificial membranes and live bacterial cells.
      The interaction kinetics was imaged using time-lapse fluorescence lifetime
      imaging of a fluorescently-tagged melittin derivative. Interaction with the
      synthetic membranes resulted in membrane pore formation. In contrast, the
      interaction with bacteria led to transient membrane disruption and corresponding
      leakage of the cytoplasm, but surprisingly with a much reduced level of pore
      formation. The discovery that pore formation is a less significant part of lipid
      peptide interaction in live bacteria highlights the mechanistic complexity of
      these interactions in living cells compared to simple artificial systems.

PMID- 23532058
TI  - A comparison of fibrin, agarose and gellan gum hydrogels as carriers of stem
      cells and growth factor delivery microspheres for cartilage regeneration.
AB  - The limited intrinsic repair capacity of articular cartilage has led to the
      investigation of different treatment options to promote its regeneration. The
      delivery of hydrogels containing stem or progenitor cells and growth factor
      releasing microspheres represents an attractive approach to cartilage repair. In
      this study, the influence of the encapsulating hydrogel on the ability of
      progenitor cells coupled with TGF-beta3 releasing microspheres to form
      cartilaginous tissue was investigated. Fibrin, agarose and gellan gum hydrogels
      containing TGF-beta3 loaded gelatin microspheres and progenitor cells derived
      from the infrapatellar fat-pad of the knee were cultured for 21 days in a
      chemically defined media. In the presence of TGF-beta3 releasing microspheres,
      gellan gum hydrogels were observed to facilitate greater cell proliferation than
      fibrin or agarose hydrogels. Histological and biochemical analysis of the
      hydrogels indicated that fibrin was the least chondro-inductive of the three
      hydrogels, while agarose and gellan gum appeared to support more robust cartilage
      formation as demonstrated by greater sGAG accumulation within these constructs.
      Gellan gum hydrogels also stained more intensely for collagen type II and
      collagen type I, suggesting that although total collagen synthesis was higher in
      these constructs, that the phenotype may be more fibrocartilaginous in nature
      than normal hyaline cartilage. This study demonstrates how the encapsulating
      hydrogel can have a significant impact on the ability of stem cells to form
      cartilage when incorporated into a growth factor delivery system.

PMID- 23532059
TI  - Evaluation of target dose based on water-equivalent thickness in external beam
      radiotherapy.
AB  - In vivo dosimetry was carried out for 152 patients receiving external beam
      radiotherapy and the treatment sites were divided into two main groups: Thorax,
      Abdomen, and Pelvic (120 fields) and Head and Neck (52 fields). Combined entrance
      and exit dose measurements were performed using LiF: Mg, Cu, P thermoluminescent
      dosimeters (TLDs). Water-equivalent (effective) thicknesses and target dose were
      evaluated using dose transmission data. The ratio of measured to expected value
      for each quantity was considered as an indicator for the accuracy of the
      parameter. The average ratio of the entrance dose was evaluated as 1.01 +/- 0.07.
      In the diameter measurement, the mean ratio of effective depth divided by the
      contour depth is 1.00 +/- 0.13 that shows a wide distribution which reflects the
      influence of contour inaccuracies as well as tissue inhomogeneities. At the
      target level, the mean ratio of measured to the prescribed dose is 1.00 +/- 0.07.
      According to our findings, the difference between effective depth and patient
      depth has a direct relation to target dose discrepancies. There are some
      inevitable sources which may cause the difference. Evaluation and application of
      effective diameter in treatment calculations would lead to a more reliable target
      dose, especially for fields which involve Thorax, Abdomen, and Pelvic.

PMID- 23532061
TI  - Blocking the butyrate-formation pathway impairs hydrogen production in
      Clostridium perfringens.
AB  - Inactivating competitive pathways will improve fermentative hydrogen production
      by obligate anaerobes, such as those of genus Clostridium. In our previous study,
      the hydrogen yield of Clostridium perfringens W13 in which l-lactate
      dehydrogenase was inactivated increased by 44% when compared with its original
      strain W12. In this study, we explored whether blocking butyrate formation
      pathway would increase hydrogen yield. The acetyl-CoA acetyltransferase gene
      (atoB) encodes the first enzyme in this pathway, which ultimately forms butyrate.
      Clostridium perfringens W14 and W15 were constructed by inactivating atoB in W13
      and W12, respectively. The hydrogen yield of W14 and W15 was 44% and 33% of those
      of W13 and W12, respectively. Inactivation of atoB decreased the pyruvate
      synthesis and its conversion to acetyl-CoA in both mutants, and increased ethanol
      formation in W14 and W15. Proteomic analysis revealed that the expressions of
      five proteins involved in butyrate formation pathway were up-regulated in W14.
      Our results suggest that butyrate formation deficiency improved ethanol
      production but not hydrogen production, indicating the importance of butyrate
      formation pathway for hydrogen production in C. perfringens.

PMID- 23532062
TI  - Molecular dynamics simulations of amyloid fibrils: an in silico approach.
AB  - Amyloid fibrils play causal roles in the pathogenesis of amyloid-related
      degenerative diseases such as Alzheimer's disease, type II diabetes mellitus, and
      the prion-related transmissible spongiform encephalopathies. The mechanism of
      fibril formation and protein aggregation is still hotly debated and remains an
      important open question in order to develop therapeutic method of these diseases.
      However, traditional molecular biological and crystallographic experiments could
      hardly observe atomic details and aggregation process. Molecular dynamics (MD)
      simulations could provide explanations for experimental results and detailed
      pathway of protein aggregation. In this review, we focus on the applications of
      MD simulations on several amyloidogenic protein systems. Furthermore, MD
      simulations could help us to understand the mechanism of amyloid aggregation and
      how to design the inhibitors.

PMID- 23532063
TI  - Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons.
AB  - Serotonin (5-HT) neurons synthesize a variety of peptides. How these peptides are
      controlled during development remains unclear. It has been reported that the co
      localization of peptides and 5-HT varies by species. In contrast to the
      situations in the rostral 5-HT neurons of human and rat brains, several peptides
      do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain. In this
      study, we found that the peptide substance P and peptide genes, including those
      encoding peptides thyrotropin-releasing hormone, enkephalin, and calcitonin gene
      related peptide, were expressed in the caudal 5-HT neurons of mouse brain; these
      findings are in line with observations in rat and monkey 5-HT neurons. We also
      revealed that these peptides/peptide genes partially overlapped with the
      transcription factor Lmx1b that specifies the 5-HT cell fate. Furthermore, we
      found that the peptide cholecystokinin was expressed in developing dopaminergic
      neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell
      fate. By examining the phenotype of Lmx1b deletion mice, we found that Lmx1b was
      required for the expression of above peptides expressed in 5-HT or dopaminergic
      neurons. Together, our results indicate that Lmx1b, a key transcription factor
      for the specification of 5-HT and dopaminergic transmitter phenotypes during
      embryogenesis, determines some peptide phenotypes in these neurons as well.

PMID- 23532064
TI  - Multifunctional open-framework zinc phosphate |C12H14N2|[Zn6(PO4)4(HPO4)(H2O)2]:
      photochromic, photoelectric and fluorescent properties.
AB  - A new open-framework zinc phosphate with 12-ring channels has been solvothermally
      synthesized by using the in situ generated methylviologen as the template, which
      exhibits multi-photoactive properties such as photochromism, photoelectricity and
      fluorescence.

PMID- 23532065
TI  - BDNF Val66Met polymorphism and anxiety/depression symptoms in schizophrenia in a
      Chinese Han population.
AB  - BACKGROUND: Although several lines of evidences suggest that the brain-derived
      neurotrophic factor (BDNF) Val66Met polymorphism may be involved in the
      pathophysiology of schizophrenia, this association remains controversial. Here,
      we aim to investigate the genetic association between the BDNF Val66Met
      polymorphism and schizophrenia and to explore whether this polymorphism could
      influence the severity of clinical symptoms in schizophrenic patients in a
      Chinese Han population. PATIENTS AND METHODS: Genotyping of the BDNF Val66Met
      polymorphism was carried out in 456 schizophrenic patients and 483 controls using
      the fluorescence resonance energy transfer method. The patients' psychotic
      symptoms were assessed using the Positive and Negative Syndrome Scale. The
      general clinical data of schizophrenic patients were analyzed. RESULTS: There
      were significant differences in the genotype distribution and allelic frequencies
      of the BDNF Val66Met polymorphism between the schizophrenia group and the
      controls. Multiple linear regression analysis showed that the BDNF Val66Met
      polymorphism explained ~16% of the variance in anxiety/depression symptoms in
      schizophrenic patients. CONCLUSION: Our data provide evidence that the BDNF
      Val66Met polymorphism may be involved in the etiology of schizophrenia in a
      Chinese Han population. Furthermore, the BDNF Val66Met polymorphism is a
      significant factor influencing the severity of anxiety/depression symptoms in
      schizophrenic patients.

PMID- 23532066
TI  - BDNF polymorphism rs11030101 is associated with the efficacy of electroconvulsive
      therapy in treatment-resistant depression.
AB  - The aim of the present study was to test for a possible association between two
      brain-derived neurotrophic factor (BDNF) polymorphisms (rs11030101 and
      rs61888800) and the efficacy of electroconvulsive therapy (ECT) [change in
      Montgomery-Asberg Depression Rating Scale (MADRS)]. So far, there are no studies
      investigating an association between these polymorphisms and the efficacy of ECT.
      The patient sample included 119 patients with treatment-resistant major
      depressive disorder who were treated with ECT. BDNF polymorphism rs11030101, but
      not rs61888800, was associated with a change in the MADRS score. Patients with
      the TA genotype of rs11030101 were less likely to benefit from ECT compared with
      patients with the TT genotype (P=0.041). The finding suggests an association
      between BDNF polymorphism rs11030101 and the efficacy of ECT. Further studies
      with larger samples will be required to confirm this finding.

PMID- 23532067
TI  - RABA members act in distinct steps of subcellular trafficking of the FLAGELLIN
      SENSING2 receptor.
AB  - Cell surface proteins play critical roles in the perception of environmental
      stimuli at the plasma membrane (PM) and ensuing signal transduction.
      Intracellular localization of such proteins must be strictly regulated, which
      requires elaborate integration of exocytic and endocytic trafficking pathways.
      Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a
      receptor that recognizes bacterial flagellin, also depends on membrane
      trafficking. However, our understanding about the mechanisms involved is still
      limited. In this study, we visualized ligand-induced endocytosis of FLS2 using
      green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana.
      Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was
      transported to a compartment with properties intermediate between the trans-Golgi
      network (TGN) and the multivesicular endosome. This compartment gradually
      discarded the TGN characteristics as it continued along the trafficking pathway.
      We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at
      different steps. Moreover, we demonstrated that transport of de novo-synthesized
      FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results
      demonstrate the complex regulatory system for properly localizing FLS2 and
      functional differentiation in RABA members in endo- and exocytosis.

PMID- 23532068
TI  - Barley MLA immune receptors directly interfere with antagonistically acting
      transcription factors to initiate disease resistance signaling.
AB  - The nucleotide binding domain and Leucine-rich repeat (NLR)-containing proteins
      in plants and animals mediate pathogen sensing inside host cells and mount innate
      immune responses against microbial pathogens. The barley (Hordeum vulgare) mildew
      A (MLA) locus encodes coiled-coil (CC)-type NLRs mediating disease resistance
      against the powdery mildew pathogen Blumeria graminis. Here, we report direct
      interactions between MLA and two antagonistically acting transcription factors,
      MYB6 and WRKY1. The N-terminal CC signaling domain of MLA interacts with MYB6 to
      stimulate its DNA binding activity. MYB6 functions as a positive regulator of
      basal and MLA-mediated immunity responses to B. graminis. MYB6 DNA binding is
      antagonized by direct association with WRKY1 repressor, which in turn also
      interacts with the MLA CC domain. The activated form of full-length MLA10
      receptor is needed to release MYB6 activator from WRKY1 repression and to
      stimulate MYB6-dependent gene expression. This implies that, while sequestered by
      the WRKY1 repressor in the presence of the resting immune receptor, MYB6 acts as
      an immediate and positive postactivation signaling component of the active state
      of MLA during transcriptional reprogramming for innate immune responses.

PMID- 23532070
TI  - Regulation of Arabidopsis leaf hydraulics involves light-dependent
      phosphorylation of aquaporins in veins.
AB  - The water status of plant leaves depends on the efficiency of the water supply,
      from the vasculature to inner tissues. This process is under hormonal and
      environmental regulation and involves aquaporin water channels. In Arabidopsis
      thaliana, the rosette hydraulic conductivity (Kros) is higher in darkness than it
      is during the day. Knockout plants showed that three plasma membrane intrinsic
      proteins (PIPs) sharing expression in veins (PIP1;2, PIP2;1, and PIP2;6)
      contribute to rosette water transport, and PIP2;1 can fully account for Kros
      responsiveness to darkness. Directed expression of PIP2;1 in veins of a pip2;1
      mutant was sufficient to restore Kros. In addition, a positive correlation, in
      both wild-type and PIP2;1-overexpressing plants, was found between Kros and the
      osmotic water permeability of protoplasts from the veins but not from the
      mesophyll. Thus, living cells in veins form a major hydraulic resistance in
      leaves. Quantitative proteomic analyses showed that light-dependent regulation of
      Kros is linked to diphosphorylation of PIP2;1 at Ser-280 and Ser-283. Expression
      in pip2;1 of phosphomimetic and phosphorylation-deficient forms of PIP2;1
      demonstrated that phosphorylation at these two sites is necessary for Kros
      enhancement under darkness. These findings establish how regulation of a single
      aquaporin isoform in leaf veins critically determines leaf hydraulics.

PMID- 23532069
TI  - Modularity of plant metabolic gene clusters: a trio of linked genes that are
      collectively required for acylation of triterpenes in oat.
AB  - Operon-like gene clusters are an emerging phenomenon in the field of plant
      natural products. The genes encoding some of the best-characterized plant
      secondary metabolite biosynthetic pathways are scattered across plant genomes.
      However, an increasing number of gene clusters encoding the synthesis of diverse
      natural products have recently been reported in plant genomes. These clusters
      have arisen through the neo-functionalization and relocation of existing genes
      within the genome, and not by horizontal gene transfer from microbes. The reasons
      for clustering are not yet clear, although this form of gene organization is
      likely to facilitate co-inheritance and co-regulation. Oats (Avena spp)
      synthesize antimicrobial triterpenoids (avenacins) that provide protection
      against disease. The synthesis of these compounds is encoded by a gene cluster.
      Here we show that a module of three adjacent genes within the wider biosynthetic
      gene cluster is required for avenacin acylation. Through the characterization of
      these genes and their encoded proteins we present a model of the subcellular
      organization of triterpenoid biosynthesis.

PMID- 23532071
TI  - The potential of text mining in data integration and network biology for plant
      research: a case study on Arabidopsis.
AB  - Despite the availability of various data repositories for plant research, a
      wealth of information currently remains hidden within the biomolecular
      literature. Text mining provides the necessary means to retrieve these data
      through automated processing of texts. However, only recently has advanced text
      mining methodology been implemented with sufficient computational power to
      process texts at a large scale. In this study, we assess the potential of large
      scale text mining for plant biology research in general and for network biology
      in particular using a state-of-the-art text mining system applied to all PubMed
      abstracts and PubMed Central full texts. We present extensive evaluation of the
      textual data for Arabidopsis thaliana, assessing the overall accuracy of this new
      resource for usage in plant network analyses. Furthermore, we combine text mining
      information with both protein-protein and regulatory interactions from
      experimental databases. Clusters of tightly connected genes are delineated from
      the resulting network, illustrating how such an integrative approach is essential
      to grasp the current knowledge available for Arabidopsis and to uncover gene
      information through guilt by association. All large-scale data sets, as well as
      the manually curated textual data, are made publicly available, hereby
      stimulating the application of text mining data in future plant biology studies.

PMID- 23532073
TI  - Supplemental digital content.

PMID- 23532074
TI  - The efficacy of patient-dependent practices on exposure rate in patients
      undergoing iodine-131 ablation.
AB  - The authors investigated the efficacy of the patient-dependent practices
      (micturition, defecation, and taking a shower) after I ablation therapy in
      patients with thyroid cancer. Exposure rates were measured from a 1-m distance at
      2, 4, and 24 h after the I administration. The comparisons for 2-4 h and 2-24 h
      time intervals were carried out among the patients with good and poor compliance,
      according to the relative amount of the patient-dependent practices, over mean
      values calculated for an effective half-life (h) or exposure rate decline ratio
      (%). In the 2-4 h interval, the mean values for good versus poor compliance were
      found to be: 4.16 h versus 8.14 h and 31% versus 17% in micturition; 5.70 h
      versus 6.84 h and 26% versus 21% in defecation; and 6.68 h versus 5.69 h and 24%
      versus 24% in taking a shower. Among patients with good versus poor compliance
      during a 2-24 h interval, the mean values were: 11.63 h versus 16.62 h and 74%
      versus 61% in micturition; 12.75 h versus 15.88 h and 71% versus 63% in
      defecation; and 13.77 h versus 14.21 h and 68% versus 67% in taking a shower.

PMID- 23532072
TI  - BR-SIGNALING KINASE1 physically associates with FLAGELLIN SENSING2 and regulates
      plant innate immunity in Arabidopsis.
AB  - Pathogen-associated molecular pattern (PAMP)-trigged immunity (PTI) is the first
      defensive line of plant innate immunity and is mediated by pattern recognition
      receptors. Here, we show that a mutation in BR-SIGNALING KINASE1 (BSK1), a
      substrate of the brassinosteroid (BR) receptor BRASSINOSTEROID INSENSITIVE1,
      suppressed the powdery mildew resistance caused by a mutation in ENHANCED DISEASE
      RESISTANCE2, which negatively regulates powdery mildew resistance and programmed
      cell death, in Arabidopsis thaliana. A loss-of-function bsk1 mutant displayed
      enhanced susceptibility to virulent and avirulent pathogens, including
      Golovinomyces cichoracearum, Pseudomonas syringae, and Hyaloperonospora
      arabidopsidis. The bsk1 mutant also accumulated lower levels of salicylic acid
      upon infection with G. cichoracearum and P. syringae. BSK1 belongs to a receptor
      like cytoplasmic kinase family and displays kinase activity in vitro; this kinase
      activity is required for its function. BSK1 physically associates with the PAMP
      receptor FLAGELLIN SENSING2 and is required for a subset of flg22-induced
      responses, including the reactive oxygen burst, but not for mitogen-activated
      protein kinase activation. Our data demonstrate that BSK1 is involved in positive
      regulation of PTI. Together with previous findings, our work indicates that BSK1
      represents a key component directly involved in both BR signaling and plant
      immunity.

PMID- 23532075
TI  - Default operational intervention levels (OILs) for severe nuclear power plant or
      spent fuel pool emergencies.
AB  - Experience and studies show that for an emergency at a nuclear power plant
      involving severe core damage or damage to the fuel in spent fuel pools, the
      following actions may need to be taken in order to prevent severe deterministic
      health effects and reduce stochastic health effects: (1) precautionary protective
      actions and other response actions for those near the facility (i.e., within the
      zones identified by the International Atomic Energy Agency) taken immediately
      upon detection of facility conditions indicating possible severe damage to the
      fuel in the core or in the spent fuel pool; and (2) protective actions and other
      response actions taken based on environmental monitoring and sampling results
      following a release. This paper addresses the second item by providing default
      operational intervention levels [OILs, which are similar to the U.S. derived
      response levels (DRLs)] for promptly assessing radioactive material deposition,
      as well as skin, food, milk and drinking water contamination, following a major
      release of fission products from the core or spent fuel pool of a light water
      reactor (LWR) or a high power channel reactor (RBMK), based on the International
      Atomic Energy Agency's guidance.

PMID- 23532076
TI  - Shielding considerations for the small animal radiation research platform
      (SARRP).
AB  - The Small Animal Radiation Research Platform (SARRP) is a commercially available
      platform designed to deliver conformal, image-guided radiation to small animals
      using a dual-anode kV x-ray source. At the University of Pennsylvania, a free
      standing 2 m enclosure was designed to shield the SARRP according to federal code
      regulating cabinet x-ray systems. The initial design consisted of 4.0-mm-thick
      lead for all secondary barriers and proved wholly inadequate. Radiation levels
      outside the enclosure were 15 times higher than expected. Additionally, the
      leakage appeared to be distributed broadly within the enclosure, so concern arose
      that a subject might receive significant doses outside the intended treatment
      field. Thus, a detailed analysis was undertaken to identify and block all sources
      of leakage. Leakage sources were identified by Kodak X-OmatV (XV) film placed
      throughout the enclosure. Radiation inside the enclosure was quantified using
      Gafchromic film. Outside the enclosure, radiation was measured using a survey
      meter. Sources of leakage included (1) an unnecessarily broad beam exiting the
      tube, (2) failure of the secondary collimator to confine the primary beam
      entirely, (3) scatter from the secondary collimator, (4) lack of beam-stop below
      the treatment volume, and (5) incomplete shielding of the x-ray tube. The exit
      window was restricted, and a new collimator was designed to address problems (1
      3). A beam-stop and additional tube shielding were installed. These modifications
      reduced internal scatter by more than 100-fold. Radiation outside the enclosure
      was reduced to levels compliant with federal regulations, provided the SARRP is
      operated using tube potentials of 175 kV or less. In addition, these simple and
      relatively inexpensive modifications eliminate the possibility of exposing a
      larger animal (such as a rat) to significant doses outside the treatment field.

PMID- 23532077
TI  - Reconstruction of long-lived radionuclide intakes for Techa riverside residents:
      137Cs.
AB  - Radioactive contamination of the Techa River (Southern Urals, Russia) occurred
      from 1949-1956 due to routine and accidental releases of liquid radioactive
      wastes from the Mayak Production Association. The long-lived radionuclides in the
      releases were Sr and Cs. Contamination of the components of the Techa River
      system resulted in chronic external and internal exposure of about 30,000
      residents of riverside villages. Data on radionuclide intake with diet are used
      to estimate internal dose in the Techa River Dosimetry System (TRDS), which was
      elaborated for the assessment of radiogenic risk for Techa Riverside residents.
      The Sr intake function was recently improved, taking into account the recently
      available archival data on radionuclide releases and in-depth analysis of the
      extensive data on Sr measurements in Techa Riverside residents. The main purpose
      of this paper is to evaluate the dietary intake of Cs by Techa Riverside
      residents. The Cs intake with river water used for drinking was reconstructed on
      the basis of the Sr intake-function and the concentration ratio Cs-to-Sr in river
      water. Intake via Cs transfer from floodplain soil to grass and cows' milk was
      evaluated for the first time. As a result, the maximal Cs intake level was
      indicated near the site of releases in upper-Techa River settlements (8,000-9,000
      kBq). For villages located on the lower Techa River, the Cs intake was
      significantly less (down to 300 kBq). Cows' milk was the main source of Cs in
      diet in the upper-Techa River region.

PMID- 23532078
TI  - Imaging doses and secondary cancer risk from kilovoltage cone-beam CT in
      radiation therapy.
AB  - The authors assessed the radiation-induced cancer risk due to organ doses from
      kilovoltage (kV) cone beam computed tomography (CBCT), a verification technique
      in image-guided radiotherapy (IGRT). CBCTs were performed for three different
      treatment sites: the head and neck, chest, and pelvis. Using a glass dosimeter,
      primary doses versus depth were measured inside a homemade phantom, and organ
      doses were measured at various locations inside an anthropomorphic phantom. The
      excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable
      risk (LAR) for cancer induction were estimated using the BEIR VII models based on
      dose measurement. The average primary (i.e., in-field) doses at the center of the
      phantom for standard imaging options were 1.9, 5.1, and 16.7 cGy for the head and
      neck, chest, and pelvis, respectively. The average secondary dose per scan for
      the pelvis measured 20-50 cm from the isocenter and ranged from 0.67-0.02 cGy,
      whereas the secondary dose per scan for the head and neck ranged from 0.07-0.003
      cGy, indicating that CBCT for treatment of the head and neck is associated with a
      smaller secondary radiation dose than CBCT for treatment of the pelvis. The
      estimation of LAR from CBCT in IGRT indicated that the lifetime cancer risk for
      major organs can reach approximately 400 per 10,000 persons if 30 CBCT scans are
      performed to position a patient during radiation treatment of the pelvis site.

PMID- 23532080
TI  - Selection of an appropriate air kerma rate constant for 75Se sources.
AB  - Monte Carlo simulation techniques using a Monte Carlo N-Particle code (MCNP5)
      analyzed six Source Production & Equipment Co., Inc., Se industrial radiography
      sources to determine an appropriate air kerma rate constant for Se, factoring in
      source encapsulation and compared to a theoretical approximation. Based on this
      study, an air kerma rate constant was calculated to be 17.7 Gy cm h Ci (0.203 R m
      h Ci), which was found to be five times lower than values published in the 1992
      Edition of the Radiological Health Handbook and Oak Ridge National Laboratory
      RISC-45. Simulations were also employed to determine the effects of self
      attenuation with the SPEC sources, the relationship between photon transmission
      values, and the thickness of various shielding materials in reducing exposure
      rates from a (75)Se source.

PMID- 23532079
TI  - GdBr3: CE in a glass wafer as a nuclear radiation monitor.
AB  - A glass wafer that contains cerium-activated gadolinium-based scintillator has
      been tested as a nuclear radiation monitor. The detector is prepared by mixing
      powdered gadolinium and cerium (3+) bromides with alumina, silica, and lithium
      fluoride, melting the mixture at 1,400 degrees C, and then quenching and
      annealing the glass. The resulting clear glass matrix emits stimulated blue light
      that can be collected by a conventional photomultiplier tube. Spectral analysis
      of radionuclides with this detector shows the energy peaks for alpha particles,
      the energy continuum for beta particles, the Compton continuum and full-energy
      peaks for gamma rays, and an energy continuum with specific reaction-product
      peaks for neutrons. Energy resolution for the 5.5-MeV alpha particle and 0.662
      MeV gamma-ray peaks is about 20%. This resolution, although threefold poorer than
      for single-crystal NaI(Tl) scintillators, contributes to radionuclide
      identification and quantification. Application of this detector to radiation
      monitoring is proposed, as well as approaches for improving light collection and
      energy resolution that will facilitate radionuclide identification and
      monitoring, especially for alpha particles, beta particles, and low-energy gamma
      rays.

PMID- 23532081
TI  - Determination and maintenance of DE minimis risk for migration of residual
      tritium (3H) from the 1969 Project Rulison nuclear test to nearby hydraulically
      fractured natural gas wells.
AB  - The Project Rulison underground nuclear test was a proof-of-concept experiment
      that was conducted under the Plowshare Program in 1969 in the Williams Fork
      Formation of the Piceance Basin in west-central Colorado. Today, commercial
      production of natural gas is possible from low permeability, natural gas bearing
      formations like that of the Williams Fork Formation using modern hydraulic
      fracturing techniques. With natural gas exploration and production active in the
      Project Rulison area, this human health risk assessment was performed in order to
      add a human health perspective for site stewardship. Tritium (H) is the
      radionuclide of concern with respect to potential induced migration from the test
      cavity leading to subsequent exposure during gas-flaring activities. This
      analysis assumes gas flaring would occur for up to 30 d and produce atmospheric H
      activity concentrations either as low as 2.2 * 10 Bq m (6 * 10 pCi m) from the
      minimum detectable activity concentration in produced water or as high as 20.7 Bq
      m (560 pCi m), which equals the highest atmospheric measurement reported during
      gas-flaring operations conducted at the time of Project Rulison. The lifetime
      morbidity (fatal and nonfatal) cancer risks calculated for adults (residents and
      workers) and children (residents) from inhalation and dermal exposures to such
      activity concentrations are all below 1 * 10 and considered de minimis. The
      implications for monitoring production water for conforming health-protective,
      risk-based action levels also are examined.

PMID- 23532087
TI  - The synthesis and properties of bifunctional and intelligent Fe3O4@titanium oxide
      core/shell nanoparticles.
AB  - A simple, one-pot solvothermal method has been demonstrated for the preparation
      of bifunctional Fe3O4@titanium oxide core/shell nanoparticles. In a typical
      procedure, tetraalkoxyl titanium Ti(OC4H9)4 and FeCl3 as precursors were added
      into ethylene glycol and further solvothermal treatment was used to synthesize
      the core/shell particles. The core/shell particles were characterized by scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      diffraction (XRD), SQUID MPMS and rheometry. The morphological results showed
      titanium oxide nanorods with 100-200 nm length and 10-20 nm diameter coated on
      the surface of 200-300 nm Fe3O4 submicrospheres. Reaction time, the titanium
      source, the barium salt etc. have an influence on the morphology of core/shell
      particles. The core/shell particles can not only respond to an external magnetic
      field, but also to an electric field--a novel application of electrorheological
      fluid.

PMID- 23532085
TI  - Assessing white matter ischemic damage in dementia patients by measurement of
      myelin proteins.
AB  - White matter ischemia is difficult to quantify histologically. Myelin-associated
      glycoprotein (MAG) is highly susceptible to ischemia, being expressed only
      adaxonally, far from the oligodendrocyte cell body. Myelin-basic protein (MBP)
      and proteolipid protein (PLP) are expressed throughout the myelin sheath. We
      compared MAG, MBP, and PLP levels in parietal white matter homogenates from 17
      vascular dementia (VaD), 49 Alzheimer's disease (AD), and 33 control brains,
      after assessing the post-mortem stability of these proteins. Small vessel disease
      (SVD) and cerebral amyloid angiopathy (CAA) severity had been assessed in
      paraffin sections. The concentration of MAG remained stable post-mortem, declined
      with increasing SVD, and was significantly lower in VaD than controls. The
      concentration of MBP fell progressively post-mortem, limiting its diagnostic
      utility in this context. Proteolipid protein was stable post-mortem and increased
      significantly with SVD severity. The MAG/PLP ratio declined significantly with
      SVD and CAA severity. The MAG and PLP levels and MAG/PLP did not differ
      significantly between AD and control brains. We validated the utility of MAG and
      MAG/PLP measurements on analysis of 74 frontal white matter samples from an
      Oxford cohort in which SVD had previously been scored. MAG concentration and the
      MAG/PLP ratio are useful post-mortem measures of ante-mortem white matter
      ischemia. 

PMID- 23532088
TI  - Bone induction by surface-double-modified true bone ceramics in vitro and in
      vivo.
AB  - True bone ceramic (TBC), obtained by twice sintering fresh bovine cancellous bone
      at high temperatures, is an osteoconductive and bioactive bone substitute
      material that exhibits excellent biocompatibility with hard tissue. The authors
      have previously synthesized a novel BMP-2-related peptide, P24, and found that it
      could enhance the osteoblastic differentiation of cells. The objective of the
      present study was to construct a double-modified TBC via mineralization into
      simulated body fluid and P24 incorporation for enhanced bone formation. In vitro
      experiments revealed that surface mineralization-modified (SMM) TBC scaffolds
      demonstrated efficiency for sustained release of P24. The P24/SMM-TBC composite
      exhibited increased osteogenic activity by cell adhesion rate determination, MTT
      assay, alkaline phosphatase staining, and calcium nodule staining with alizarin
      red compared with SMM-TBC and TBC. In vivo studies showed that the P24/SMM-TBC
      composite scaffold promoted significant bone defect repair, in marked contrast to
      stand-alone SMM-TBC and TBC, based on the results of radiographic evaluation and
      histological examination. These findings indicate that SMM-TBC is a good scaffold
      for the controlled release of P24 and that the P24/SMM-TBC composite could
      improve the adhesion, proliferation and differentiation of cells and repair bone
      defects. The double-modified P24/SMM-TBC composite biomaterial shows potential
      for clinical application in bone tissue engineering.

PMID- 23532086
TI  - TIMP-1 attenuates blood-brain barrier permeability in mice with acute liver
      failure.
AB  - Blood-brain barrier (BBB) dysfunction in acute liver failure (ALF) results in
      increased BBB permeability that often precludes the patients from obtaining a
      life-saving liver transplantation. It remains controversial whether matrix
      metalloproteinase-9 (MMP-9) from the injured liver contributes to the
      deregulation of BBB function in ALF. We selectively upregulated a physiologic
      inhibitor of MMP-9 (TIMP-1) with a single intracerebroventricular injection of
      TIMP-1 cDNA plasmids at 48 and 72 hours, or with pegylated-TIMP-1 protein. Acute
      liver failure was induced with tumor necrosis factor-alpha and D-(+)
      galactosamine in mice. Permeability of BBB was assessed with sodium fluorescein
      (NaF) extravasation. We found a significant increase in TIMP-1 within the central
      nervous system (CNS) after the administration of TIMP-1 cDNA plasmids and that
      increased TIMP-1 within the CNS resulted in an attenuation of BBB permeability, a
      reduction in activation of epidermal growth factor receptor and p38 mitogen
      activated protein kinase signals, and a restoration of the tight junction protein
      occludin in mice with experimental ALF. Pegylated TIMP-1 provided similar
      protection against BBB permeability in mice with ALF. Our results provided a
      proof of principle that MMP-9 contributes to the BBB dysfunction in ALF and
      suggests a potential therapeutic role of TIMP-1 in ALF. 

PMID- 23532090
TI  - Enantioselective tandem reaction of chromone-derived Morita-Baylis-Hillman
      carbonates with benzylamines catalyzed by a trifunctional organocatalyst: the
      synthesis of chiral 3-aminomethylene-flavanones.
AB  - An enantioselective tandem reaction of chromones-derived MBH carbonates (1) with
      benzylamines (2) catalyzed by a trifunctional organocatalyst, cinchonidine-amide
      thiourea, has been developed in moderate to good yields (50-87%) and
      enantioselectivities (up to 89% ee).

PMID- 23532089
TI  - UV-radiation induced disruption of dry-cavities in human gammaD-crystallin
      results in decreased stability and faster unfolding.
AB  - Age-onset cataracts are believed to be expedited by the accumulation of UV
      damaged human gammaD-crystallins in the eye lens. Here we show with molecular
      dynamics simulations that the stability of gammaD-crystallin is greatly reduced
      by the conversion of tryptophan to kynurenine due to UV-radiation, consistent
      with previous experimental evidences. Furthermore, our atomic-detailed results
      reveal that kynurenine attracts more waters and other polar sidechains due to its
      additional amino and carbonyl groups on the damaged tryptophan sidechain, thus
      breaching the integrity of nearby dry center regions formed by the two Greek key
      motifs in each domain. The damaged tryptophan residues cause large fluctuations
      in the Tyr-Trp-Tyr sandwich-like hydrophobic clusters, which in turn break
      crucial hydrogen-bonds bridging two beta-strands in the Greek key motifs at the
      "tyrosine corner". Our findings may provide new insights for understanding of the
      molecular mechanism of the initial stages of UV-induced cataractogenesis.

PMID- 23532091
TI  - Curcumin induces cross-regulation between autophagy and apoptosis in uterine
      leiomyosarcoma cells.
AB  - OBJECTIVE: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard
      chemotherapy. A natural occurring compound, curcumin, has been shown to have
      inhibitory effects on cancers. We previously demonstrated that curcumin reduced
      uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating
      apoptosis. To further explore the anticancer effect of curcumin, we investigated
      the efficacy of curcumin on autophagy in LMS cells. METHODS: Cell proliferation
      in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to
      rapamycin or curcumin. Autophagy was detected by Western blotting for light chain
      3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western
      blotting for cleaved poly (ADP-ribose) polymerase (PARP). RESULTS: Both rapamycin
      and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose
      dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1
      cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased
      extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells,
      whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal
      regulated kinase 1/2 pathway and curcumin-induced autophagy. CONCLUSIONS: These
      experimental findings suggest that curcumin is a potent inhibitor of cell
      proliferation in uterine LMS and provide new insights about ongoing signaling
      events leading to the possible development of a new therapeutic agent.

PMID- 23532092
TI  - Treatment Strategies for Patients with Diffuse Large B-Cell Lymphoma: Past,
      Present, and Future.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring lymphoma in
      the Western world. DLBCL is a clinically, biologically, and pathologically
      heterogeneous entity with biologically distinct subtypes that have different
      expected treatment outcomes. The addition of rituximab to combination
      chemotherapy has improved outcomes for all patients with DLBCL and can produce
      cure for many individuals. Relapsed DLBCL is generally managed with salvage chemo
      immunotherapy followed by high dose therapy and autologous stem cell
      transplantation which can cure additional patients. However, outcomes for
      patients who relapse early after upfront rituximab and chemotherapy have a poorer
      prognosis. Novel therapies and strategies are desperately needed for these
      patients and several emerging treatments hold promise for improving DLBCL
      treatment outcomes in the future.

PMID- 23532094
TI  - Development of temporally refined land-use regression models predicting daily
      household-level air pollution in a panel study of lung function among asthmatic
      children.
AB  - Regulatory monitoring data and land-use regression (LUR) models have been widely
      used for estimating individual exposure to ambient air pollution in epidemiologic
      studies. However, LUR models lack fine-scale temporal resolution for predicting
      acute exposure and regulatory monitoring provides daily concentrations, but fails
      to capture spatial variability within urban areas. This study coupled LUR models
      with continuous regulatory monitoring to predict daily ambient nitrogen dioxide
      (NO(2)) and particulate matter (PM(2.5)) at 50 homes in Windsor, Ontario. We
      compared predicted versus measured daily outdoor concentrations for 5 days in
      winter and 5 days in summer at each home. We also examined the implications of
      using modeled versus measured daily pollutant concentrations to predict daily
      lung function among asthmatic children living in those homes. Mixed effect
      analysis suggested that temporally refined LUR models explained a greater
      proportion of the spatial and temporal variance in daily household-level outdoor
      NO(2) measurements compared with daily concentrations based on regulatory
      monitoring. Temporally refined LUR models captured 40% (summer) and 10% (winter)
      more of the spatial variance compared with regulatory monitoring data. Ambient
      PM(2.5) showed little spatial variation; therefore, daily PM(2.5) models were
      similar to regulatory monitoring data in the proportion of variance explained.
      Furthermore, effect estimates for forced expiratory volume in 1 s (FEV(1)) and
      peak expiratory flow (PEF) based on modeled pollutant concentrations were
      consistent with effects based on household-level measurements for NO(2) and
      PM(2.5). These results suggest that LUR modeling can be combined with continuous
      regulatory monitoring data to predict daily household-level exposure to ambient
      air pollution. Temporally refined LUR models provided a modest improvement in
      estimating daily household-level NO(2) compared with regulatory monitoring data
      alone, suggesting that this approach could potentially improve exposure
      estimation for spatially heterogeneous pollutants. These findings have important
      implications for epidemiologic studies - in particular, for research focused on
      short-term exposure and health effects.

PMID- 23532095
TI  - Boosting HIV treatment options: good news, new challenges.

PMID- 23532096
TI  - Effects of linezolid on suppressing in vivo production of staphylococcal toxins
      and improving survival outcomes in a rabbit model of methicillin-resistant
      Staphylococcus aureus necrotizing pneumonia.
AB  - BACKGROUND:  Linezolid is recommended for treatment of pneumonia and other
      invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA).
      The premise underlying this recommendation is that linezolid inhibits in vivo
      production of potent staphylococcal exotoxins, including Panton-Valentine
      leukocidin (PVL) and alpha-hemolysin (Hla), although supporting evidence is
      lacking. METHODS:  A rabbit model of necrotizing pneumonia using MRSA clone
      USA300 was used to compare therapeutic effects of linezolid (50 mg/kg 3
      times/day) and vancomycin (30 mg/kg 2 times/day) administered 1.5, 4, and 9 hours
      after infection on host survival outcomes and in vivo bacterial toxin production.
      RESULTS:  Mortality rates were 100% for untreated rabbits and 83%-100% for
      vancomycin-treated rabbits. In contrast, mortality rates were 25%, 50%, and 100%
      for rabbits treated with linezolid 1.5, 4, and 9 hours after infection,
      respectively. Compared with untreated and vancomycin-treated rabbits, improved
      survival of rabbits treated 1.5 hours after infection with linezolid was
      associated with a significant decrease in bacterial counts, suppressed bacterial
      production of PVL and Hla, and reduced production of the neutrophil
      chemoattractant interleukin 8 in the lungs. CONCLUSIONS:  Across the study
      interval, only early treatment with linezolid resulted in significant suppression
      of exotoxin synthesis and improved survival outcomes in a rabbit model of MRSA
      necrotizing pneumonia.

PMID- 23532097
TI  - Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus
      emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1
      infected patients: week 48 results.
AB  - BACKGROUND:  Cobicistat (COBI) is a pharmacoenhancer with no antiretroviral
      activity in vitro. METHODS:  An international, randomized, double-blind, double
      dummy, active-controlled trial was conducted to evaluate the efficacy and safety
      of COBI versus ritonavir (RTV) as a pharmacoenhancer of atazanavir (ATV) in
      combination with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in
      treatment-naive patients. The primary end point was a human immunodeficiency
      virus type 1 (HIV-1) RNA load of <50 copies/mL at week 48 by the Food and Drug
      Administration snapshot algorithm; the noninferiority margin was 12%. RESULTS:  A
      total of 692 patients were randomly assigned to a treatment arm and received
      study drug (344 in the COBI group vs 348 in the RTV group). At week 48, virologic
      success was achieved in 85% of COBI recipients and 87% of RTV recipients
      (difference, -2.2% [95% confidence interval, -7.4% to 3.0%]); among patients with
      a baseline HIV-1 RNA load of >100 000 copies/mL, rates were similar (86% vs 86%).
      Similar percentages of patients in both groups had serious adverse events (10% of
      COBI recipients vs 7% of RTV recipients) and adverse events leading to
      discontinuation of treatment with the study drug (7% vs 7%). Median increases in
      the serum creatinine level were 0.13 and 0.09 mg/dL, respectively, for COBI and
      RTV recipients. CONCLUSIONS:  COBI was noninferior to RTV in combination with ATV
      plus FTC/TDF at week 48. Both regimens achieved high rates of virologic success.
      Safety and tolerability profiles of the 2 regimens were comparable. Once-daily
      COBI is a safe and effective pharmacoenhancer of the protease inhibitor ATV.

PMID- 23532098
TI  - Expression of Pneumocystis jirovecii major surface glycoprotein in Saccharomyces
      cerevisiae.
AB  - The major surface glycoprotein (Msg), which is the most abundant protein
      expressed on the cell surface of Pneumocystis organisms, plays an important role
      in the attachment of this organism to epithelial cells and macrophages. In the
      present study, we expressed Pneumocystis jirovecii Msg in Saccharomyces
      cerevisiae, a phylogenetically related organism. Full-length P. jirovecii Msg was
      expressed with a DNA construct that used codons optimized for expression in
      yeast. Unlike in Pneumocystis organisms, recombinant Msg localized to the plasma
      membrane of yeast rather than to the cell wall. Msg expression was targeted to
      the yeast cell wall by replacing its signal peptide, serine-threonine-rich
      region, and glycophosphatidylinositol anchor signal region with the signal
      peptide of cell wall protein alpha-agglutinin of S. cerevisiae, the serine
      threonine-rich region of epithelial adhesin (Epa1) of Candida glabrata, and the
      carboxyl region of the cell wall protein (Cwp2) of S. cerevisiae, respectively.
      Immunofluorescence analysis and treatment with beta-1,3 glucanase demonstrated
      that the expressed Msg fusion protein localized to the yeast cell wall. Surface
      expression of Msg protein resulted in increased adherence of yeast to A549
      alveolar epithelial cells. Heterologous expression of Msg in yeast will
      facilitate studies of the biologic properties of Pneumocystis Msg.

PMID- 23532099
TI  - Methamphetamine alters blood brain barrier protein expression in mice,
      facilitating central nervous system infection by neurotropic Cryptococcus
      neoformans.
AB  - Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive
      central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique
      interface that in part functions to prevent microbial invasion of the CNS. The
      effects of METH on brain vasculature have not been studied extensively. We
      hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS
      infection. Using a murine model of METH administration, we demonstrated that METH
      alters BBB integrity and modifies the expression of tight junction and adhesion
      molecules. Additionally, we showed that BBB disruption accelerates transmigration
      of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after
      systemic infection. Furthermore, METH-treated mice displayed increased mortality
      as compared to untreated animals. Our findings provide novel evidence of the
      impact of METH abuse on the integrity of the cells that comprise the BBB and
      protect the brain from infection. 

PMID- 23532100
TI  - The role of staphylothrombin-mediated fibrin deposition in catheter-related
      Staphylococcus aureus infections.
AB  - Staphylococcus aureus (S. aureus) is a frequent cause of catheter-related
      infections. S. aureus secretes the coagulases staphylocoagulase and von
      Willebrand factor-binding protein, both of which form a staphylothrombin complex
      upon binding to prothrombin. Although fibrinogen and fibrin facilitate the
      adhesion of S. aureus to catheters, the contribution of staphylothrombin-mediated
      fibrin has not been examined. In this study, we use a S. aureus mutant lacking
      both coagulases (Deltacoa/vwb) and dabigatran, a pharmacological inhibitor of
      both staphylothrombin and thrombin, to address this question. Genetic absence or
      chemical inhibition of pathogen-driven coagulation reduced both fibrin deposition
      and the retention of S. aureus on catheters in vitro. In a mouse model of jugular
      vein catheter infection, dabigatran reduced bacterial load on jugular vein
      catheters, as well as metastatic kidney infection. Importantly, inhibition of
      staphylothrombin improved the efficacy of vancomycin treatment both in vitro and
      in the mouse model.

PMID- 23532101
TI  - Differential cell line susceptibility to the emerging novel human betacoronavirus
      2c EMC/2012: implications for disease pathogenesis and clinical manifestation.
AB  - The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently
      isolated from patients with severe pneumonia and renal failure and was associated
      with an unexplained high crude fatality rate of 56%. We performed a cell line
      susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human
      respiratory tract (polarized airway epithelium cell line Calu-3, embryonic
      fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney
      (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma
      cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and
      histiocytes (malignant histiocytoma cell line His-1), as evident by detection of
      high or increasing viral load in culture supernatants, detection of viral
      nucleoprotein expression by immunostaining, and/or detection of cytopathic
      effects. Although an infected human neuronal cell line (NT2) and infected
      monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral
      loads, their relatively lower viral production corroborated with absent
      nucleoprotein expression and cytopathic effects. This range of human tissue
      tropism is broader than that for all other HCoVs, including SARS coronavirus,
      HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high
      mortality associated with this disease. A recent cell line susceptibility study
      showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may
      jump interspecies barriers. We found that HCoV-EMC can also infect civet lung
      fibroblast and rabbit kidney cell lines. These findings have important
      implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.

PMID- 23532102
TI  - Enhanced acute immune response in IL-12p35-/- mice is followed by accelerated
      distinct repair mechanisms in Staphylococcus aureus-induced murine brain abscess.
AB  - BACKGROUND: Murine Staphylococcus aureus-mediated brain abscess comprises 2 major
      phases, an initial phase of cerebritis, followed by a healing phase characterized
      by capsule formation. METHODS: C57BL/6 wild-type (WT) and IL-12p35(-/-) mice were
      intracerebrally infected with S. aureus to induce brain abscesses. Clinical
      disease activity and bacterial load were monitored. The cell populations that
      were involved, as well as their specific mediators, were analyzed by
      immunohistochemistry, quantitative real-time polymerase chain reaction, and flow
      cytometry. RESULTS: In the acute phase, IL-12p35(-/-) mice were protected from
      disease. This was associated with enhanced recruitment of granulocytes,
      accompanied by upregulated expression of Il17a, Csf2 (which encodes granulocyte
      macrophage colony-stimulating factor), Cxcl1, and Cxcl5, as well as increased
      expression of proinflammatory mediators, including Nos2 (which encodes inducible
      nitric oxide synthase), Ptgs2 (which encodes cyclooxygenase 2), and Tnf, that
      were primarily produced by granulocytes and activated microglia/macrophages.
      Furthermore, mechanisms associated with beneficial wound healing, including an
      accelerated formation of a fibrous capsule, were demonstrated by prominent VEGF-A
      production and collagen deposition driven by an earlier onset of T-helper 2
      immunity in the absence of interleukin 12 (IL-12). CONCLUSIONS: Brain abscess
      development is orchestrated by IL-12 at different stages of disease. Our data
      indicate that IL-12 has a nonprotective role in the acute phase and that IL-12
      deficiency results in the accelerated formation of a protective capsule during
      the healing phase, which we consider crucial for early recovery from disease.

PMID- 23532103
TI  - A new virulent human coronavirus: how much does tissue culture tropism tell us?

PMID- 23532104
TI  - Photoinduced electron transfer of platinum(II) bipyridine diacetylides linked by
      triphenylamine- and naphthaleneimide-derivatives and their application to
      photoelectric conversion systems.
AB  - The recently reported efficient charge-separated system based on bipyridine
      diacetylide platinum(ii) complexes was applied to photoelectric conversion
      systems herein, based on the design and synthesis of two triads: MTA-Pt-NDISAc
      (3, MTA: dimethoxytriphenylamine, Pt: platinum(ii) complex, NDISAc: thioacetate
      derivative linked to naphthalenediimide) and MTA-Pt-MNICOOH (4, MNICOOH:
      naphthaleneimide-4-carboxylic acid). The charge-separated (CS) states of triads 3
      and 5 (MOM-protected 4) were effectively generated by photo-induced electron
      transfer in both THF and toluene, although the rate of formation of the CS state
      from 5 was relatively slow in toluene. The lifetimes of these CS states were
      determined to be 730 ns in toluene and 61 ns (70%) and 170 ns (30%) as a double
      exponential decay in THF for 3, and 600 ns in toluene and 170 ns in THF for 5.
      The acetylthio group of triad 3 was exploited in the preparation of a self
      assembled monolayer (SAM) on a gold surface. Photocurrent was detected upon
      irradiation of an electrochemical cell comprising Au/3/Na ascorbate/Pt, which was
      ascribed to the platinum(ii) complex based on the action spectrum. The carboxylic
      acid group of triad 4 facilitated adsorption on the TiO2 surface, and a dye
      sensitized solar cell constructed based on FTO/TiO2/4/electrolyte (LiI-I2)/Pt
      exhibited a poor energy conversion efficiency (eta = 0.20%) based on the incident
      photon-to-current conversion efficiency spectrum and the I-V curve. This poor
      efficiency may be derived from the bent molecular shape of 4, or may be due to a
      possible high energy barrier in the electron injection process through the
      adsorption site.

PMID- 23532105
TI  - Liver transplantation for neuroendocrine tumors in Europe-results and trends in
      patient selection: a 213-case European liver transplant registry study.
AB  - OBJECTIVE: The purpose of this study was to assess outcomes and indications in a
      large cohort of patients who underwent liver transplantation (LT) for liver
      metastases (LM) from neuroendocrine tumors (NET) over a 27-year period.
      BACKGROUND: LT for NET remains controversial due to the absence of clear
      selection criteria and the scarcity and heterogeneity of reported cases. METHODS:
      This retrospective multicentric study included 213 patients who underwent LT for
      NET performed in 35 centers in 11 European countries between 1982 and 2009. One
      hundred seven patients underwent transplantation before 2000 and 106 after 2000.
      Mean age at the time of LT was 46 years. Half of the patients presented hormone
      secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone
      surgical treatment of the primary tumor and/or LM and 76% had received
      chemotherapy. The median interval between diagnosis of LM and LT was 25 months
      (range, 1-149 months). In addition to LT, 24 patients underwent major resection
      procedures and 30 patients underwent minor resection procedures. RESULTS: Three
      month postoperative mortality was 10%. At 5 years after LT, overall survival (OS)
      was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS
      was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is,
      major resection in addition to LT, poor tumor differentiation, and hepatomegaly.
      Since 2000, 5-year OS has increased to 59% in relation with fewer patients
      presenting poor prognostic factors. Multivariate analysis of the 106 cases
      treated since 2000 identified the following predictors of poor outcome:
      hepatomegaly, age more than 45 years, and any amount of resection concurrent with
      LT. CONCLUSIONS: LT is an effective treatment of unresectable LM from NET.
      Patient selection based on the aforementioned predictors can achieve a 5-year OS
      between 60% and 80%. However, use of overly restrictive criteria may deny LT to
      some patients who could benefit. Optimal timing for LT in patients with stable
      versus progressive disease remains unclear.

PMID- 23532106
TI  - Liver transplantation for unresectable metastases to the liver: a new era in
      transplantation or a time for caution?

PMID- 23532107
TI  - Pathohistological subtype predicts survival in patients with intraductal
      papillary mucinous neoplasm (IPMN) of the pancreas.
AB  - OBJECTIVE: To investigate different subtypes of intraductal papillary mucinous
      neoplasms (IPMNs) of the pancreas and their prognostic value. BACKGROUND: IPMNs
      of the pancreas are estimated to have a better prognosis than pancreatic ductal
      adenocarcinomas (PDACs). In addition to the different growth types (ie, main duct
      vs. branch duct types), the histological subtypes of IPMNs (ie, intestinal,
      pancreatobiliary, gastric, and oncocytic type) are prognostically relevant. These
      subtypes can be characterized by different mucin (MUC) expression patterns. In
      this study, we analyzed the IPMNs from 2 pancreatic cancer referral centers by
      correlating the MUC expression, histological subtype, and clinical outcome.
      METHODS: We re-evaluated all resections due to a pancreatic tumor over a period
      of 15 years. Cases with IPMNs were identified, and the subtypes were
      distinguished using histopathological analysis, including the immunohistochemical
      analysis of MUC (ie, MUC1, MUC2, and MUC5AC) expression. Furthermore, we
      determined clinical characteristics and patient outcome. RESULTS: A total of 103
      IPMNs were identified. On the basis of the MUC profile, histopathological
      subtypes were classified into the following categories: intestinal type [n = 45
      (44%)], pancreatobiliary type [n = 41 (40%)], gastric type [n = 13 (12%)], and
      oncocytic type [n = 4 (4%)]. The following types of resections were performed:
      pancreatic head resections [n = 77 (75%)], tail resections [n = 16 (15%)], total
      pancreatectomies [n = 5 (5%)], and segment resections [n = 5 (5%)]. The 5-year
      survival of patients with intestinal IPMNs was significantly better than
      pancreatobiliary IPMNs (86.6% vs. 35.6%; P < 0.001). The pancreatobiliary subtype
      was strongly associated with malignancy [odds ratio (OR): 6.76], recurrence (P <
      0.001), and long-term survival comparable with that of PDAC patients.
      CONCLUSIONS: Evaluation of IPMN subtypes supports postoperative patient prognosis
      prediction. Therefore, subtype differentiation could lead to improvements in
      clinical management. Potentially identifying subgroups with the need for adjuvant
      therapy may be possible.

PMID- 23532108
TI  - Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic
      ductal adenocarcinomas are frequently of gastric subtype.
AB  - OBJECTIVE: To identify a high-risk group of patients with pancreatic ductal
      adenocarcinoma (PDAC), independently arising in the pancreas with intraductal
      papillary mucinous neoplasm (IPMN), using histopathologic subtypes. BACKGROUND:
      Pathologic features of IPMN with distinct PDAC, including histopathologic
      subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin
      expression patterns and the mutational status of GNAS and KRAS are useful to
      explore the relationship between these 2 lesion types. METHODS: Clinicopathologic
      data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control
      group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate
      grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes
      (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1,
      MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs
      and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was
      evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs. RESULTS: Twenty
      six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with
      IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric
      type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%),
      pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both
      PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6
      expression, as assessed by immunohistochemistry, but were negative for MUC2 and
      CDX2. The mucin-staining patterns were similar to those of invasive tubular
      adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201
      was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited
      KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal
      type IPMN with distinct PDAC. CONCLUSIONS: Mucin expression patterns demonstrate
      that PDAC without GNAS mutations of an aggressive phenotype frequently arise in
      the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.

PMID- 23532109
TI  - Enhanced-reality video fluorescence: a real-time assessment of intestinal
      viability.
AB  - OBJECTIVE: Our aim was to evaluate a fluorescence-based enhanced-reality system
      to assess intestinal viability in a laparoscopic mesenteric ischemia model.
      MATERIALS AND METHODS: A small bowel loop was exposed, and 3 to 4 mesenteric
      vessels were clipped in 6 pigs. Indocyanine green (ICG) was administered
      intravenously 15 minutes later. The bowel was illuminated with an incoherent
      light source laparoscope (D-light-P, KarlStorz). The ICG fluorescence signal was
      analyzed with Ad Hoc imaging software (VR-RENDER), which provides a digital
      perfusion cartography that was superimposed to the intraoperative laparoscopic
      image [augmented reality (AR) synthesis]. Five regions of interest (ROIs) were
      marked under AR guidance (1, 2a-2b, 3a-3b corresponding to the ischemic,
      marginal, and vascularized zones, respectively). One hour later, capillary blood
      samples were obtained by puncturing the bowel serosa at the identified ROIs and
      lactates were measured using the EDGE analyzer. A surgical biopsy of each
      intestinal ROI was sent for mitochondrial respiratory rate assessment and for
      metabolites quantification. RESULTS: Mean capillary lactate levels were 3.98 (SD
      = 1.91) versus 1.05 (SD = 0.46) versus 0.74 (SD = 0.34) mmol/L at ROI 1 versus 2a
      2b (P = 0.0001) versus 3a-3b (P = 0.0001), respectively. Mean maximal
      mitochondrial respiratory rate was 104.4 (+/-21.58) pmolO2/second/mg at the ROI 1
      versus 191.1 +/- 14.48 (2b, P = 0.03) versus 180.4 +/- 16.71 (3a, P = 0.02)
      versus 199.2 +/- 25.21 (3b, P = 0.02). Alanine, choline, ethanolamine, glucose,
      lactate, myoinositol, phosphocholine, sylloinositol, and valine showed
      statistically significant different concentrations between ischemic and
      nonischemic segments. CONCLUSIONS: Fluorescence-based AR may effectively detect
      the boundary between the ischemic and the vascularized zones in this experimental
      model.

PMID- 23532110
TI  - A prognostic nomogram for prediction of recurrence in desmoid fibromatosis.
AB  - OBJECTIVE: To construct a postoperative nomogram to estimate the risk of local
      recurrence for patients with desmoid tumors. BACKGROUND: The standard management
      of desmoid tumors is resection, but many recur locally. Other options include
      observation or novel chemotherapeutics, but little guidance exists on selecting
      treatment. METHODS: Patients undergoing resection during 1982-2011 for primary or
      locally recurrent desmoids were identified from a single-institution prospective
      database. Cox regression analysis was used to assess risk factors and to create a
      recurrence nomogram, which was validated using an international, multi
      institutional data set. RESULTS: Desmoids were treated surgically in 495 patients
      (median follow-up of 60 months). Of 439 patients undergoing complete gross
      resection, 100 (23%) had recurrence. Five-year local recurrence-free survival was
      69%. Eight patients died of disease, all after R2 resection. Adjuvant radiation
      was not associated with improved local recurrence-free survival. In multivariate
      analysis, factors associated with recurrence were extremity location, young age,
      and large tumor size, but not margin. Abdominal wall tumors had the best outcome
      (5-year local recurrence-free survival rate of 91%). Age, site, and size were
      used to construct a nomogram with concordance index of 0.703 in internal
      validation and 0.659 in external validation. Integration of additional variables
      (R1 margin, sex, depth, and primary vs recurrent presentation) did not
      importantly improve concordance (internal concordance index of 0.707).
      CONCLUSIONS: A postoperative nomogram including only size, site, and age predicts
      local recurrence and can aid in counseling patients. Systemic therapies may be
      appropriate for young patients with large, extremity desmoids, but surgery alone
      is curative for most abdominal wall lesions.

PMID- 23532111
TI  - Impact of histologically confirmed lymph node metastases on patient survival
      after surgical resection for hepatocellular carcinoma: report of a Japanese
      nationwide survey.
AB  - OBJECTIVE: To clarify the clinical significance of resection of lymph node
      metastases in patients' hepatocellular carcinoma (HCC). BACKGROUND: Although the
      presence of lymph node metastasis form HCC has been considered as a systemic
      disease, prognosis after resection of them remains unknown. METHODS: From the
      database of a Japanese nationwide survey, 14,872 patients of HCC treated by
      surgical resection between 2000 and 2005 were enrolled. We modified the current
      Japanese staging system for HCC, by further dividing stage IVA into stage IVAnon
      n1 and stage n1, according to the absence or presence of pathologically proven
      lymph node metastasis. Thus, the patients classified into 6 disease stages, that
      is, I (n=1494), II (n=8056), III (n=4243), IVAnon-n1 (n=701), n1 (n=112), and IVB
      (n=266), and their long-term outcomes were compared. RESULTS: The median follow
      up period was 20.6 months. The 3-year overall survival rates of the patients with
      stage IVAnon-n1, stage n1, and stage IVB were 51.6%, 38.9% and 27.2%,
      respectively. A multivariate analysis showed that stage IVAnon-n1 would have a
      similar impact on the survival as stage n1 (hazard ratio: 0.88, 95% confidence
      interval: 0.59-1.33, P=0.555), and that stage n1 still represented one class less
      advanced than stage IVB (hazard ratio: 0.52, 95% confidence interval: 0.34-0.80,
      P=0.003). CONCLUSIONS: The prognosis of patients with histologically node
      positive HCC was similar to that of patients with locally advanced HCC (stage
      IVA), which supports the validity of the current Japanese staging system and also
      partially validates the system proposed by the UICC/AJCC.

PMID- 23532112
TI  - Prognostic value of the new International Association for the Study of Lung
      Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma
      classification on death and recurrence in completely resected stage I lung
      adenocarcinoma.
AB  - OBJECTIVE: This study investigated the prognostic value of the new International
      Association for the Study of Lung Cancer, American Thoracic Society, and European
      Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in
      resected stage I lung adenocarcinoma. METHODS: Histological classification of 283
      patients undergoing surgical resection for stage I lung adenocarcinoma was
      determined according to the IASLC/ATS/ERS classification after comprehensive
      histological subtyping with recording of the percentage of each histological
      component (lepidic, acinar, papillary, micropapillary, and solid) in 5%
      increments. Their impact on overall survival, recurrence, and postrecurrence
      survival was investigated. RESULTS: The 5-year overall survival and recurrence
      free rates were 81.6% and 76.9%, respectively. During follow-up, 57 (20.1%)
      patients developed recurrence. The 2-year postrecurrence survival rate was 72.3%.
      The solid predominant group is associated with significant more male sex, higher
      smoking exposure, larger tumor size, and more poorly differentiated histological
      grade. Lepidic predominant group had significantly better overall survival (P =
      0.002). Micropapillary and solid predominant groups had significantly lower
      probability of freedom from recurrence (P = 0.004). Older age (P = 0.039),
      visceral pleural invasion to the surface (PL2) (P = 0.009), and high grade
      (micropapillary/solid predominant) of the new classification (P = 0.028) were
      predictors of recurrence in multivariate analysis. The solid predominant group
      tends to have significantly worse postrecurrence survival (P = 0.074).
      CONCLUSIONS: The new adenocarcinoma classification has significant impact on
      death and recurrence in stage I lung adenocarcinoma. Patients with PL2 and
      micropapillary/solid predominant pattern have significant higher risk for
      recurrence. This information is important for patient stratification for
      aggressive adjuvant chemoradiation therapy.

PMID- 23532113
TI  - Critical review of 'Public domain application': a flexible drug approval system
      in Japan.
AB  - BACKGROUND: 'Public domain application' is a flexible drug approval system in
      Japan, similar to the fast track designation in the United States. METHODS: From
      1999 to 2009, four drugs and three regimens received approval from 'Public domain
      application'. The data from the review reports were extracted, and the reviewing
      process was critically re-evaluated. RESULTS: The study drugs were categorized
      into three groups according to the sizes of the studies and evidence levels in
      the original articles that were submitted. Carboplatin was categorized into the
      first group with a large number of study patients and a high evidence level; the
      review report had studies with more than 15 000 total patients and 8 phase III
      studies. The ifosfamide and vinblastine regimen was categorized into the second
      group, with a low number of study patients and a low evidence level; the review
      report had studies with less than 1000 total patients and 1 phase III study.
      Dacarbazine; cytarabine; methotrexate, vinblastine, doxorubicin, and cisplatin;
      bleomycin, etoposide, and cisplatin; and fludarabine were categorized into the
      remaining third group, with a moderate number of study patients and evidence
      level. CONCLUSIONS: Drugs with various backgrounds, including evidence levels and
      physicians' experiences, were approved via 'Public domain application'. The
      approvals of most drugs were evaluated to be appropriate.

PMID- 23532114
TI  - A novel classification of colorectal tumors based on microsatellite instability,
      the CpG island methylator phenotype and chromosomal instability: implications for
      prognosis.
AB  - BACKGROUND: We studied the overlap between the major (epi)genomic events
      microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and
      chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific
      (epi)genotypes were associated with CRC-related deaths. PATIENTS AND METHODS:
      Molecular analyses using tumor DNA were successful in 509 CRC cases identified
      within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the
      vital status until May 2005 was 100%. RESULTS: MSI (12.6%), CIMP-only (5.3%),
      CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed
      significantly regarding tumor localization, differentiation grade, initial
      adjuvant therapy (AT) use and genetic characteristics (P <= 0.03). CIMP-only,
      CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were
      significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related
      deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35
      4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were
      borderline significantly associated with a 0.40-fold risk of CRC-related deaths
      after late follow-up (95% CI 0.15-1.03). CONCLUSION(S): This is the first study
      to show that specific (epi)genotypes may hold a differential prognostic value
      that may vary over time. Although no specific treatment data were available, an
      explanation for the differential findings over time might be that (epi)genotypes
      modify therapy response.

PMID- 23532115
TI  - Effect of low-dose tamoxifen after surgical excision of ductal intraepithelial
      neoplasia: results of a large retrospective monoinstitutional cohort study.
AB  - BACKGROUND: Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with
      standard doses of tamoxifen has not reached a consensus yet. Given positive
      results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed
      a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as
      per institutional guidelines. PATIENTS AND METHODS: All consecutive women
      operated on at the European Institute of Oncology for estrogen receptor (ER)
      positive DIN (474 treated with low-dose tamoxifen and 509 untreated patients)
      were followed up for a median of 7 years. RESULTS: Compared with untreated
      patients, a significant 30% reduction in breast cancer risk was observed on low
      dose tamoxifen with an adjusted hazard ratio (HR) = 0.70 [95% confidence interval
      (CI) 0.51-0.94], with a greater benefit in postmenopausal (HR = 0.57; 95% CI 0.34
      0.94) than in premenopausal women (HR = 0.79; 95% CI 0.54-1.17). Treated patients
      with ER and progesterone receptor (PgR) >50% DIN had a lower incidence of breast
      events than untreated ones (HR = 0.61; 95% CI 0.40-0.94), whereas no protective
      effect has been observed in patients with ER or PgR <50% DIN. Drug
      discontinuation resulted in a doubled risk of recurrence in premenopausal women
      only (HR = 1.95; 95% CI 0.98-3.89). No excess of endometrial cancer occurred.
      CONCLUSIONS: Low-dose tamoxifen is a promising and safe strategy for highly
      endocrine responsive DIN. Treatment adherence is crucial in premenopausal women.
      A definitive trial is ongoing.

PMID- 23532118
TI  - Patient perceptions of physician reimbursement for spine surgery.
AB  - STUDY DESIGN: Anonymous patient survey. OBJECTIVE: To determine what patients
      think surgeons should be paid to perform elective spine surgical procedures, and
      gauge awareness of actual Medicare reimbursement. SUMMARY OF BACKGROUND DATA:
      With increasing transparency, the public may become aware of physician
      reimbursements and may be a part of the debate regarding appropriate
      reimbursement. It is unknown what patients perceive that spinal surgeons deserve
      to be, or are actually, paid to perform spinal procedures. METHODS: Two hundred
      anonymous surveys were given to consecutive patients in an outpatient office
      setting by means of convenience sampling. Patients were asked how much they think
      physicians are and should be reimbursed for typical spine procedures; and they
      were asked about their opinions of the actual reimbursement amount for these
      procedures. It was made explicit that the fee in question included only the
      surgeon's reimbursement and not that of the hospital. Data were tabulated,
      statistical comparisons were made, and results were correlated with demographic
      information. RESULTS: On average, respondents thought that surgeons should be
      paid $21,299 for performing a lumbar discectomy and estimated that Medicare
      actually pays $12,336 (actual average reimbursement $971). Similar disparities
      were seen for the other procedures.The vast majority of respondents thought that
      the average Medicare reimbursement for spine procedures was too low. For example,
      92.2% of patients thought that $971 for a lumbar discectomy was "too low," 6.1%
      thought it was "about right," and only 1.6% thought that $971 was "too high."
      CONCLUSION: Patients think that orthopedic spine surgeons should be compensated
      over 10 to 20 times more than current Medicare reimbursement rates. Patients
      overestimate the actual amount that Medicare reimburses by a factor of
      approximately 7 to 10. Less than 10% of patients think that the current Medicare
      payment is about right, and less than 2% think that surgeons are overpaid.

PMID- 23532117
TI  - TAK1 regulates autophagic cell death by suppressing the phosphorylation of p70 S6
      kinase 1.
AB  - There is growing interest in identifying regulators of autophagy. The molecular
      mechanism underlying transforming growth factor-beta activated kinase 1 (TAK1)
      induced autophagy is poorly understood. We found that TAK1 inhibits p70 S6
      kinase1 (S6K1) phosphorylation by interfering interaction of raptor with S6K1,
      thus inducing autophagy. The factors that determine whether autophagy is
      cytoprotective or cytotoxic have not been fully elucidated. In Drosophila, TAK1
      overexpression leads to an impaired eye phenotype despite inhibition of
      apoptosis, indicating that the phenotype was mainly due to autophagy. Also, TAK1
      overexpression increases lactate dehydrogenase (LDH) level in mammalian cells.
      When treated with autophagy inhibitors, the level of TAK1-induced cytotoxicity or
      cell death was significantly attenuated, indicating that TAK1 induces cytotoxic
      autophagic cell death. This study provides the first in vitro and in vivo
      evidence of TAK1-induced autophagy and we believe that our findings significantly
      contribute to the understanding of the mechanisms underlying the induction of
      autophagy.

PMID- 23532116
TI  - Chernobyl cleanup workers from Estonia: follow-up for cancer incidence and
      mortality.
AB  - This study examined cancer incidence (1986-2008) and mortality (1986-2011) among
      the Estonian Chernobyl cleanup workers in comparison with the Estonian male
      population. The cohort of 4810 men was followed through nationwide population,
      mortality and cancer registries. Cancer and death risks were measured by
      standardised incidence ratio (SIR) and standardised mortality ratio (SMR),
      respectively. Poisson regression was used to analyse the effects of year of
      arrival, duration of stay and time since return on cancer and death risks. The
      SIR for all cancers was 1.06 with 95% confidence interval 0.93-1.20 (232 cases).
      Elevated risks were found for cancers of the pharynx, the oesophagus and the
      joint category of alcohol-related sites. No clear evidence of an increased risk
      of thyroid cancer, leukaemia or radiation-related cancer sites combined was
      apparent. The SMR for all causes of death was 1.02 with 95% confidence interval
      0.96-1.08 (1018 deaths). Excess mortality was observed for mouth and pharynx
      cancer, alcohol-related cancer sites together and suicide. Duration of stay
      rather than year of arrival was associated with increased mortality. Twenty-six
      years of follow-up of this cohort indicates no definite health effects
      attributable to radiation, but the elevated suicide risk has persisted.

PMID- 23532119
TI  - Loads worn by soldiers predict episodes of low back pain during deployment to
      Afghanistan.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To describe low back pain
      (LBP) sustained by soldiers deployed to Afghanistan and identify demographic,
      fitness, and occupational risk factors of LBP. SUMMARY OF BACKGROUND DATA: LBP is
      the most common injury in deployed soldiers. It results in lost duty days,
      medical evacuations, and permanent disability. Risk factors for LBP have not been
      investigated in this population. METHODS: This study investigated a US Army
      Brigade Combat Team deployed to Afghanistan for 1 year. Demographic, fitness, and
      occupational variables were recorded before and after deployment. Episodes of LBP
      were assessed using self-report data. Logistic regression was used to investigate
      predictors of (1) moderate or worse LBP developed during deployment and (2) all
      LBP developed during deployment. RESULTS: The incidence of moderate or worse LBP
      was 22% in the 805 soldiers studied. Soldiers with elevated risk of LBP were
      male, in Cavalry or Infantry units, wore body armor for more than 6 hr/d, worked
      at a desk for 1 to 4 hours a day, spent 5 to 8 hr/d lifting, spent more than 1
      hr/wk on walking patrol, spent 21 to 40 hr/wk in a tactical vehicle, or wore
      equipment. The most parsimonious set of significant predictors for moderate or
      worse LBP included age, OR = 1.04 (1.01-1.08); fitness score, OR = 0.99 (0.989
      0.999); the amount of time spent wearing body armor, OR = 1.16 (1.10-1.23); the
      amount of time spent on walking patrol, OR = 1.01 (1.003-1.02); and weight of the
      equipment worn, OR = 1.01 (1.002-1.013). The incidence of all LBP (minor or
      worse) was 77%. The most parsimonious set of significant predictors for all LBP
      included age, OR = 1.06 (1.02-1.09); fitness score, OR = 0.99 (0.985-0.997);
      history of LBP, OR = 2.94, (1.87-4.62); equipment weight, OR = 1.008 (1.003
      1.01); and time spent wearing body armor, OR = 1.13 (1.07-1.19). CONCLUSION: This
      study found that being older, having lower fitness scores, wearing armor longer,
      and wearing heavier loads increased the risk of LBP in deployed soldiers. Units
      more likely to wear loads such as the Infantry and Cavalry and tasks commonly
      involving wearing loads such as patrolling all increased the risk of LBP as well.

PMID- 23532120
TI  - Pre- and postoperative lower extremity motor power and ambulatory status of
      patients with spinal cord compression due to a metastatic spinal tumor.
AB  - STUDY DESIGN: Retrospective review of medical records. OBJECTIVE: To describe pre
      and postoperative ambulatory status and lower limb motor power, and compare
      characteristics of patients with metastatic spinal cord compression (MSCC) who
      were ambulatory at 48 hours postoperatively with those of patients with MSCC who
      were nonambulatory. SUMMARY OF BACKGROUND DATA: Preoperative motor power of the
      lower extremities is a predictor of postoperative ambulatory status in patients
      with MSCC. METHODS: We retrospectively evaluated the medical records of 102
      consecutive patients with MSCC who presented for decompressive surgery with lower
      extremity weakness between January 1997 and December 2010. A single surgeon
      classified the preoperative and 48-hour postoperative motor power of the lower
      extremities on a 6-point scale. Ambulation status was determined 48 hours after
      surgery and patients were classified as ambulatory (including normal ambulation,
      ambulation with aid, and ambulation without aid) or nonambulatory. Demographic
      and clinical characteristics were compared between patients who were ambulatory
      and those who were nonambulatory at 48 hours postoperatively. RESULTS: Motor
      power was improved 1.05 +/- 0.73 grades after operation. Two-thirds of patients
      who were preoperatively classified as nonambulatory were ambulatory at 48 hours
      postoperatively. The only significantly different affecting factor between the
      postoperative ambulatory group and the nonambulatory group was preoperative lower
      extremity power and preoperative capability of ambulation. In addition, grade III
      of lower extremity motor power was significant criteria for postoperative
      ambulation. CONCLUSION: We recommend aggressive decompressive surgery in patients
      with MSCC if preoperative lower extremity motor power is at least grade III,
      although all groups of preoperative lower extremity motor power had 1 or more
      patients who returned to ambulation. LEVEL OF EVIDENCE: 3.

PMID- 23532122
TI  - Ossifications after vertical expandable prosthetic titanium rib treatment in
      children with thoracic insufficiency syndrome and scoliosis.
AB  - STUDY DESIGN: Retrospective analysis of 1328 spinal radiographs of 57 patients
      after vertical expandable prosthetic titanium rib (VEPTR) implantation with an
      average follow-up of 30 months. OBJECTIVE: To evaluate the incidence, time of
      onset, as well as the underlying factors influencing the occurrence of
      ossifications in children treated with VEPTR. SUMMARY OF BACKGROUND DATA:
      Spontaneous spinal fusions and ossifications are well known in children treated
      with spinal implants. In theory, children with spinal deformity and VEPTR
      implantation are less likely to develop these complications because of either
      little or no implant contact to the spine. METHODS: Fifty-seven patients had a
      primary VEPTR implantation due to spinal deformity and thoracic insufficiency
      syndrome and repeated lengthening procedures. The mean age at the time of primary
      surgery was 7.7 years, the mean duration of follow-up was 29.8 months, and the
      mean number of operations was 5.9. A total of 1328 spinal radiographs were
      analyzed with respect to the occurrence and growth of ossifications, implant
      migration, and other complications. RESULTS: Overall, 24% of the patients (n =
      13) had ossifications, which affected in 92% the main load sharing VEPTR implant.
      The fusions involved in 54% of cases the lumbar spine and in each 23% the ribs
      and the iliac crest. Ossifications developed in 11% of children within the first
      year of treatment and increased by about the same rate per annum. After 53
      months, 48% of the radiographs showed some ossifications. There was a significant
      correlation to the stiffness of the deformity and the number of surgical
      procedures. CONCLUSION: Contrary to previous assumptions, it was shown that in
      children treated with the VEPTR system, 48% of children showed ossifications
      after 53 months. Ossifications were observed significantly more often in children
      with stiff deformities and after multiple surgical procedures. It is a much more
      common problem than previously thought. LEVEL OF EVIDENCE: 3.

PMID- 23532124
TI  - A hospital policy for procedural sedation in the nonintubated patient.

PMID- 23532125
TI  - Controversies and considerations in formulating a hospital policy for procedural
      sedation.

PMID- 23532126
TI  - A program for education, competency, and quality in procedural sedation.

PMID- 23532127
TI  - Pharmacologic choices for procedural sedation.

PMID- 23532128
TI  - Sedation of critically ill patients undergoing mechanical ventilation.

PMID- 23532129
TI  - Perioperative uses of dexmedetomidine.

PMID- 23532130
TI  - Procedural sedation for adult dental procedures.

PMID- 23532131
TI  - Procedural sedation for interventional cardiology procedures.

PMID- 23532132
TI  - Pediatric sedation outside the operating room.

PMID- 23532134
TI  - Preface: procedural sedation.

PMID- 23532136
TI  - Effect of source/sink ratios on yield components, growth dynamics and structural
      characteristics of oil palm (Elaeis guineensis) bunches.
AB  - Source/sink ratios are known to be one of the main determinants of oil palm
      growth and development. A long-term experiment (9 years) was conducted in
      Indonesia on mature oil palms subjected to continuous bunch ablation and partial
      defoliation treatments to artificially modify source/sink ratios. During the
      experiment, all harvested bunches were dissected and phenological measurements
      were carried out to analyse the effect of source/sink ratios on yield components
      explaining variations in bunch number, the number of fruits per bunch and oil dry
      weight per fruit. An integrative variable (supply/demand ratio) describing the
      ratio between the assimilate supply from sources and the growing organ demand for
      carbohydrate was computed for each plant on a daily basis from observations of
      the number of developing organs and their sink strength, and of climate
      variables. Defoliation and bunch ablation affected the bunch number and the fruit
      number per bunch. Variations in bunch number per month were mainly due to
      variations in the fraction of aborted inflorescence and in the ratio between
      female and male inflorescences. Under fluctuating trophic conditions, variations
      in fruit number per bunch resulted both from changes in fruit-set and in the
      number of branches (rachillae) per inflorescence. For defoliated plants, the
      decrease in the number of developing reproductive sinks appeared to be sufficient
      to maintain fruit weight and oil concentration at the control level, without any
      major decrease in the concentration of non-structural carbohydrate reserves.
      Computation of the supply/demand ratio revealed that each yield component had a
      specific phase of sensitivity to supply/demand ratios during inflorescence
      development. Establishing quantitative relationships between supply/demand
      ratios, competition and yield components is the first step towards a functional
      model for oil palm.

PMID- 23532135
TI  - Isoprene function in two contrasting poplars under salt and sunflecks.
AB  - In the present study, biogenic volatile organic compound (BVOC) emissions and
      photosynthetic gas exchange of salt-sensitive (Populus x canescens (Aiton) Sm.)
      and salt-tolerant (Populus euphratica Oliv.) isoprene-emitting and non-isoprene
      emitting poplars were examined under controlled high-salinity and high
      temperature and -light episode ('sunfleck') treatments. Combined treatment with
      salt and sunflecks led to an increased isoprene emission capacity in both poplar
      species, although the photosynthetic performance of P. * canescens was reduced.
      Indeed, different allocations of isoprene precursors between the cytosol and the
      chloroplast in the two species were uncovered by means of (13)CO2 labeling.
      Populus * canescens leaves, moreover, increased their use of 'alternative' carbon
      (C) sources in comparison with recently fixed C for isoprene biosynthesis under
      salinity. Our studies show, however, that isoprene itself does not have a
      function in poplar survival under salt stress: the non-isoprene-emitting leaves
      showed only a slightly decreased photosynthetic performance compared with wild
      type under salt treatment. Lipid composition analysis revealed differences in the
      double bond index between the isoprene-emitting and non-isoprene-emitting
      poplars. Four clear metabolomics patterns were recognized, reflecting systemic
      changes in flavonoids, sterols and C fixation metabolites due to the
      lack/presence of isoprene and the absence/presence of salt stress. The studies
      were complemented by long-term temperature stress experiments, which revealed the
      thermotolerance role of isoprene as the non-isoprene-emitting leaves collapsed
      under high temperature, releasing a burst of BVOCs. Engineered plants with a low
      isoprene emission potential might therefore not be capable of resisting high
      temperature episodes. 

PMID- 23532137
TI  - Ternary modified TiO2 as a simple and efficient photocatalyst for green organic
      synthesis.
AB  - TiO2 ternary-modified with Fe(3+), Ni(2+), and Au nanoparticles exhibited a
      noticeable photocatalytic activity for selective cyclohexane oxidation with O2
      under sunlight irradiation.

PMID- 23532139
TI  - Influence of bilateral sequential total knee arthroplasty on functional recovery.
AB  - BACKGROUND: Main concerns of patients undergoing bilateral surgery is the quantum
      of pain and the progress of functional recovery. We studied functional recovery
      in terms of pain, range of motion (ROM), SF12, WOMAC scores and a unique TUG
      (timed up and go) test for patients undergoing unilateral total knee arthroplasty
      (U/L-TKA) and sequential bilateral total knee arthroplasty (B/L-TKA). MATERIALS
      AND METHODS: Three groups of 77 consecutive patients (91 knees) were
      retrospectively compared. They were B/L TKA group (28 knees: 14 patients),
      Unilateral TKA group with contralateral knee nonoperated i.e., U/L-TKA group (42
      knees) and Unilateral TKA with contralateral TKA already done i.e., U/L + C/L TKA
      group (21 knees). Patients were assessed preoperatively and on postoperative days
      3, 5, 14, 42, 90 and 1 year. RESULTS: The WOMAC score was statistically better
      preoperatively in the U/L + C/L TKA group, and SF12 MCS score was statistically
      better preoperatively in the B/L-TKA group. The TUG test time in the B/L-TKA
      group was statistically longer on days 3 and 5 as compared to other groups and
      became comparable by day 14. The TUG score became better than the preoperative
      value by day 42 in the B/L-TKA group, which took 90 days in other groups.
      CONCLUSION: The early functional recovery of bilateral TKA patient lags behind
      that of unilateral TKA patient for the first 5 days, becomes equal by the 14(th)
      day and remains equal till 1 year after surgery. Bilateral TKA patients regain
      their preoperative functional status by 6 weeks against 3 months for unilateral
      TKA. The operative status of the contralateral knee makes no difference to early
      functional recovery after unilateral TKA. With bilateral TKA, there is no
      difference in pain and ROM parameters.

PMID- 23532143
TI  - Fluid and sodium balance of elite wheelchair rugby players.
AB  - Blood sodium concentration of tetraplegics during exercise has not been
      investigated. This study aimed to measure blood sodium changes in relation to
      fluid intakes and thermal comfort in tetraplegics during wheelchair rugby
      training. Twelve international male wheelchair rugby players volunteered, and
      measures were taken during 2 training sessions. Body mass, blood sodium
      concentration, and subjective thermal comfort using a 10-point scale were
      recorded before and after both training sessions. Fluid intake and the distance
      covered were measured during both sessions. The mean (SD) percentage changes in
      body mass during the morning and afternoon training sessions were +0.4%1 (0.65%)
      and +0.69% (1.24%), respectively. There was a tendency for fluid intake rate to
      be correlated with the percentage change in blood sodium concentration (p = .072,
      r2 = .642) during the morning training session; this correlation reached
      significance during the afternoon session (p = .004, r2 = .717). Fluid intake was
      significantly correlated to change in thermal comfort in the morning session (p =
      .018, r2 = .533), with this correlation showing a tendency in the afternoon
      session (p = .066, r2 = .151). This is the first study to investigate blood
      sodium concentrations in a group of tetraplegics. Over the day, blood sodium
      concentrations significantly declined; 2 players recorded blood sodium
      concentrations of 135 mmol/L, and 5 recorded blood sodium concentrations of 136
      mmol/L. Excessive fluid intake as a means of attenuating thermal discomfort seems
      to be the primary cause of low blood sodium concentrations in tetraplegic
      athletes. Findings from this study could aid in the design of fluid-intake
      strategies for tetraplegics.

PMID- 23532145
TI  - Environmental temperature and exercise-induced blood oxidative stress.
AB  - Previous research findings indicate that environmental temperature can influence
      exercise-induced oxidative-stress responses, although the response to variable
      temperatures is unknown. The purpose of this study was to investigate the effect
      of warm, cold, and "neutral," or room, environmental temperatures on the blood
      oxidative stress associated with exercise and recovery. Participants (N = 12, age
      27 +/- 5 yr, VO2max = 56.7 +/- 5.8 ml . kg-1 . min-1, maximal cycle power output
      = 300 +/- 39 W) completed 3 exercise sessions consisting of a 1-hr ride at 60%
      Wmax, at 40% relative humidity in warm (33  degrees C), cold (7  degrees C), and
      room-temperature environments (20  degrees C) in a randomized crossover fashion.
      Rectal core temperature was monitored continually as participants remained in the
      respective trial temperature throughout a 3-hr recovery. Blood was collected
      preexercise and immediately, 1 hr, and 3 hr postexercise and analyzed for
      oxidative-stress markers including ferric-reducing ability of plasma (FRAP),
      Trolox-equivalent antioxidant capacity (TEAC), lipid hydroperoxides, and protein
      carbonyls. Core temperature was significantly elevated by all exercise trials,
      but recovery core temperatures reflected the given environment. FRAP (p < .001),
      TEAC (p < .001), and lipid hydroperoxides (p < .001) were elevated after warm
      exercise while protein carbonyls were not altered (p > .05). These findings
      indicate that moderate-intensity exercise and associated recovery in a warm
      environment elicits a blood oxidative-stress response not observed at comparable
      exercise performed at lower temperatures.

PMID- 23532146
TI  - Reverse effects of DPI administration combined with glutamine supplementation on
      function of rat neutrophils induced by overtraining.
AB  - PURPOSE: To examine the excessive reactive oxygen species (ROS) mediated by
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the combined
      effect of glutamine supplementation and diphenyleneiodonium (DPI) on the function
      of neutrophils induced by overtraining. METHODS: Fifty male Wistar rats were
      randomly divided into 5 groups: control group (C), overtraining group (E), DPI
      administration group (D), glutamine-supplementation group (G), and combined DPI
      and glutamine group (DG). Blood was sampled from the orbital vein after rats were
      trained on treadmill for 11 wk. Cytokine and lipid peroxidation in blood plasma
      were measured by enzyme-linked immunosorbent assay. The colocalization between
      gp91phox and p47phox of the NADPH oxidase was detected using immunocytochemistry
      and confocal microscopy. The activity of NADPH oxidase was assessed by
      chemiluminescence. Neutrophils' respiratory burst and phagocytosis function were
      measured by flow cytometry. RESULTS: NADPH oxidase was activated by overtraining.
      Cytokine and lipid peroxidation in blood plasma and the activity of NADPH oxidase
      were markedly increased in Group E compared with group C. Neutrophil function was
      lower in group E than group C. Both lower neutrophils function and higher ROS
      production were reversed in Group DG. The glutamine and DPI interference alone in
      group D and group G was less effective than DPI and glutamine combined in group
      DG. CONCLUSION: Activation of NADPH oxidase is responsible for the production of
      superoxide anions, which leads to excessive ROS and is related to the decrease in
      neutrophil function induced by overtraining. The combined DPI administration and
      glutamine supplementation reversed the decreased neutrophil function after
      overtraining.

PMID- 23532151
TI  - Enzyme immobilisation in biocatalysis: why, what and how.
AB  - In this tutorial review, an overview of the why, what and how of enzyme
      immobilisation for use in biocatalysis is presented. The importance of
      biocatalysis in the context of green and sustainable chemicals manufacture is
      discussed and the necessity for immobilisation of enzymes as a key enabling
      technology for practical and commercial viability is emphasised. The underlying
      reasons for immobilisation are the need to improve the stability and
      recyclability of the biocatalyst compared to the free enzyme. The lower risk of
      product contamination with enzyme residues and low or no allergenicity are
      further advantages of immobilised enzymes. Methods for immobilisation are divided
      into three categories: adsorption on a carrier (support), encapsulation in a
      carrier, and cross-linking (carrier-free). General considerations regarding
      immobilisation, regardless of the method used, are immobilisation yield,
      immobilisation efficiency, activity recovery, enzyme loading (wt% in the
      biocatalyst) and the physical properties, e.g. particle size and density,
      hydrophobicity and mechanical robustness of the immobilisate, i.e. the
      immobilised enzyme as a whole (enzyme + support). The choice of immobilisate is
      also strongly dependent on the reactor configuration used, e.g. stirred tank,
      fixed bed, fluidised bed, and the mode of downstream processing. Emphasis is
      placed on relatively recent developments, such as the use of novel supports such
      as mesoporous silicas, hydrogels, and smart polymers, and cross-linked enzyme
      aggregates (CLEAs). 

PMID- 23532152
TI  - Primary chondrosarcoma of the breast: report of a case and review of the
      literature.
AB  - Sarcomas of the breast are rare, comprising 1% of all breast tumors. Primary
      chondrosarcomas of the breast account for an extremely rare subset of such
      tumors, with few reports in the literature. We report the case of a 52 year-old
      woman with a primary chondrosarcoma of the breast and review the current
      literature.

PMID- 23532155
TI  - Comment on "visceral leishmaniasis in a rheumatoid arthritis patient treated with
      methotrexate".

PMID- 23532156
TI  - Soil-based systemic delivery and phyllosphere in vivo propagation of
      bacteriophages: Two possible strategies for improving bacteriophage persistence
      for plant disease control.
AB  - Soil-based root applications and attenuated bacterial strains were evaluated as
      means to enhance bacteriophage persistence on plants for bacterial disease
      control. In addition, the systemic nature of phage applied to tomato roots was
      also evaluated. Several experiments were conducted applying either single phages
      or phage mixtures specific for Ralstonia solanacearum, Xanthomonas perforans or
      X. euvesicatoria to soil surrounding tomato plants and measuring the persistence
      and translocation of the phages over time. In general, all phages persisted in
      the roots of treated plants and were detected in stems and leaves; although phage
      level varied and persistence in stems and leaves was at a much lower level
      compared with persistence in roots. Bacterial wilt control was typically best if
      the phage or phage mixtures were applied to the soil surrounding tomatoes at the
      time of inoculation, less effective if applied 3 days before inoculation, and
      ineffective if applied 3 days after inoculation. The use of an attenuated X.
      perforans strain was also evaluated to improve the persistence of phage
      populations on tomato leaf surfaces. In greenhouse and field experiments, foliar
      applications of an attenuated mutant X. perforans 91-118:?OPGH strain prior to
      phage applications significantly improved phage persistence on tomato foliage
      compared with untreated tomato foliage. Both the soil-based bacteriophage
      delivery and the use of attenuated bacterial strains improved bacteriophage
      persistence on respective root and foliar tissues, with evidence of translocation
      with soil-based bacteriophage applications. Both strategies could lead to
      improved control of bacterial pathogens on plants.

PMID- 23532157
TI  - [Revival or default risk of public health?].

PMID- 23532158
TI  - Chemical and microbiological monitoring of air in two waste incineration plants.
AB  - The study evaluated emissions from two incinerator plants and occupational
      exposure of workers during a six-year monitoring period (2004-2009). Chemical and
      microbiological analyses were performed by collecting environmental and staff
      individual air samples. Inspirable and respirable particulate and metals were
      measured in both environmental and staff samples; concentrations of Volatile
      Organic Compounds and the presence of microorganisms were investigated only in
      environmental samples. The concentrations of all organic and inorganic compounds
      investigated were very low and always below the Italian legal limits and the
      threshold limits recommended by the American Conference of Governmental
      Industrial Hygienists. In addition, microbial contamination was generally low in
      all the working areas considered. Study results revealed a good quality of air in
      the incineration plants and no apparent risk situation for the workers.

PMID- 23532159
TI  - [Cancer survival in a local health district in Piemonte (Italy): follow up to
      2007].
AB  - The objectives of this study were to compare, in a standardized manner, survival
      of cancer patients residing in this area and to further verify the quality of
      baseline incidence and mortality data. The survival analysis presented here
      refers to cases of primary malignant tumors diagnosed for the first time from
      2002 to 2004 and followed until 31 December 2007. Women were found to have lower
      survival rates for gastric, laryngeal and lung cancer with respect to men while
      good survival rates were found for cancers for which organized screening programs
      are available. Overall, results show that women in this health district have
      substantially lower survival than men, indicating that major efforts in terms of
      primary prevention and awareness should be geared at this population.

PMID- 23532160
TI  - [Monitoring of heavy metals and trace elements in the air, fruits and vegetables
      and soil in the province of Catania (Italy)].
AB  - Contamination of fruits and vegetables with heavy metals can result from
      anthropogenic events (car or factory emissions, poor management of sewage and
      industrial waste) or from natural events (volcanic activity and geological soil
      matrix). The chemical and toxicological characteristics of heavy metals can have
      an impact on human health through several mechanisms. Other metals, on the other
      hand, are essential for maintenance of physiological and biochemical human
      processes, are protective against many diseases and must be present in the diet
      because they cannot be synthesized by the human body. The purpose of this study
      was to assess the presence of heavy metals and trace elements both in fruit and
      vegetable products widely consumed in the province of Catania (Sicily, Italy) and
      in various environmental matrices (air, water and land), and to investigate
      possible sources of contamination. Fruit and vegetable products (tomatoes,
      lettuce, spinach, eggplants, potatoes, zucchini, grapes, apples and pears) were
      sampled (n = 60) from the towns of Adrano, Biancavilla and Mazzarrone. These
      locations were selected for their geomorphology, climate and cultivation
      characteristics. Levels of lead, cadmium, nickel, copper, zinc, vanadium and
      selenium in fruit, vegetables, air and water samples were determined using atomic
      absorption spectrometer with graphite furnace Perkin-Elmer AAnalyst 800 while
      soil samples were evaluated by the atomic emission spectrometer Optima 2000 DV
      Perkin-Elmer. The presence of mercury was evaluated by atomic absorption
      spectrometry with cold vapor technique. Study results revealed widespread
      contamination of fruit and vegetables and mainly due to use of fertilizers and to
      volcanic activity. A strategy targeting the entire food chain is essential for
      ensuring food safety and consumer protection and maintaining contaminants at
      levels which are not hazardous to health.

PMID- 23532161
TI  - [Evaluation of genotoxic effects in subjects occupationally exposed to
      antineoplastic drugs].
AB  - The present molecular epidemiology study was carried out to evaluate the
      genotoxic effects of occupational exposure to antineoplastic drugs (ANP). The
      study was conducted in 52 hospital workers involved in the preparation, handling
      or administration of ANP in a hospital in Perugia (central Italy) and in 52 non
      exposed control subjects matched for age, gender and smoking habits to the
      exposed subjects. Both comet assay and the micronucleus test were used to
      evaluate genome damage in peripheral blood lymphocytes in study subjects. The
      extent of primary DNA damage, as evaluated by the comet assay, was significantly
      increased in exposed personnel with respect to matched controls. On the other
      hand, no significant differences in micronuclei frequency was observed between
      the two groups. Multivariate linear regression analysis showed an association
      between years of occupational exposure over 10 years and higher extent of primary
      DNA damage in the exposed group. The results of this study confirm that handling
      ANP without appropriate precautions carries a genotoxic risk for exposed
      healthcare workers. These results address the need for regular biological effect
      monitoring of staff occupationally-exposed to ANP.

PMID- 23532162
TI  - [Active surveillance of invasive pneumococcal diseases in Sicilian children (2009
      2011)].
AB  - S.pneumoniae is a major cause of morbidity and mortality among children globally.
      Since 2007 the World Health Organization has recommended anti-pneumococcal
      vaccination to reduce the burden of invasive pneumococcal diseases (IPD). The aim
      of this study was to estimate the incidence of IPD in Sicilian children and
      describe the distribution of serotypes in subjects with IPD following the recent
      introduction of a universal vaccination program. Active surveillance of IPD
      (PneumoNet) was carried out in Sicily from 2009 to 2011 by nine reference
      hospitals (one per province) and one-hundred randomly sampled family
      pediatricians. Hospital discharge data of participating hospitals were also
      analyzed and compared with regional surveillance data. During the three-year
      surveillance period, 136 children with a M/F ratio of 1.03 and a median age of
      23.5 months (range 1-57 months), were included in the study (14 in 2009, 66 in
      2010 and 56 in 2011). Of the 136 subjects, 43 (36.1%) were recruited from FPs
      whereas 93 (63.9%) from hospital personnel. Overall, 9 children (6.6%) were
      positive for IPD. S. pneumoniae serotype 19A was isolated from three children,
      serotype 15C from three, and serotype 23F from one child. Hospital discharge data
      from 2009 to 2011 showed that a diagnosis of IPD was reported for 18 of 2,663
      subjects, with decreasing annual trend from 1.1% in 2009 to 0.3% in 2011 (Chi
      square for trend p=0.063). In conclusion, PneumoNet is shown to be an effective
      tool for identifying children with IPD. The estimated incidence of IPD in Sicily
      is lower than that observed in other Italian and European regions, especially
      before vaccine introduction. These results indicate a good level of pneumococcal
      disease control in the Sicilian population below 5 years of age and support the
      implementation of an universal vaccination program. Considering the emergence of
      serotypes 19A PCV13 vaccine may offer some advantages with respect to the seven
      valent pneumococcal conjugate vaccine (PCV7) which does not include 19A.

PMID- 23532163
TI  - [Hospital-territorial services and integration of health care: the Protected
      Discharge program in the Umbria Region from 2005 to 2010].
AB  - In order to address the management of patients with chronic diseases, national
      and international regulatory guidelines have developed policies and operational
      tools aimed at integration and implementation of pathways of continuity of health
      care between different healthcare settings. "Protected Discharge" programs have
      been developed for the organized transfer of patients from one setting of care
      (hospital) to another (territory) in order to ensure their continuity of care and
      assistance. The aim of this study was to assess the degree of implementation the
      program in the context of continuity of healthcare in the Umbria region (Italy).
      An analysis of the regional archive of hospital discharge records was performed
      to examine trends of the various types of hospital discharges during the years
      2005 to 2010. A slow but steady increase of protected discharges was observed
      from 2005 (0.9%) to 2010 (1.9%). The percentages observed are higher than those
      at the national level (except for transfer to RSA); however, results indicate
      insufficient implementation of hospital-territorial services integration and
      hence of the principle of continuity of health and social care.

PMID- 23532164
TI  - [Health Promotion and care of immigrant population in the eighth Municipality of
      Rome: the experience of the Medicine Service of Solidarity and the University
      Hospital of Tor Vergata].
AB  - The VIII Municipality of Rome is characterized by a high poverty rate, by the
      presence of many immigrant communities and by the lack of health services
      available to vulnerable social groups. In 2005 , the " Servizio di Medicina
      Solidale" of the University Hospital of "Tor Vergata", for the first time
      intervened in this Municipality regarding Immigrant Health. The paper describes
      the activities and organization of this service from January 2005 to December
      2007. It demonstrates a complex epidemiological picture of 2,374 immigrants,
      characterized by a young population, mostly women with reproductive health
      issues, followed by children with infectious and nutritional problems and,
      ultimately, adults who accessed the service, firstly for gastroenterological
      problems, secondly for cardiovascular problems and finally for dysmetabolic
      disorders. The paper describes the culture-centered actions of Health Promotion
      and Health Education in order to improve health awareness and promote integration
      of immigrants. The study indicates that the limited number of hospital admissions
      ( n.20) with respect to the number of outpatient visits (n.70.000) in the first
      seven years of the service " Medicina Solidale" has significantly reduced the
      number of unnecessary admissions to emergency wards. In conclusion it is notable
      that the cost of such intervention results eight times inferior to emergency
      admissions and further confirms that a Community medicine approach is
      sustainable.

PMID- 23532165
TI  - [A health promotion program aimed at employees and restaurant operators: results
      of the European FOOD project].
AB  - Public health is facing a major challenge: the fight against overweight and
      obesity. Many projects have been developed and implemented all over the world.
      FOOD is one of the most important European programs to promote a healthy
      lifestyle and a balanced diet in the workplace. The program aims to improve the
      nutritional quality of the food offered in restaurants and to facilitate consumer
      choice by educating and informing employers and their employees. Different
      channels, tools and countries have been involved in this program which took place
      over the course of two years and is ongoing due to the high value of the applied
      methodology.

PMID- 23532166
TI  - [National Vaccine Prevention Plan (PNPV) 2012-2014 in the Italian Regions].
AB  - Seven years after the previous National Vaccines Plan (PNV) 2005-2007 the new
      PNPV 2012-2014 was ratified with the approval of both National and Regional
      Authorities in February 22, 2012. The implementation state of the new Plan at
      31/12/2012 was evaluated in all Italian Regions. The regional situations of the
      new strategies introduced by the Plan regarding Human Papillomavirus,
      pneumococcal, meningococcal and varicella vaccines are described. This analysis
      indicates that in the field of immune prevention a better interregional
      coordination is needed, to achieve an efficient Italian vaccination strategy.

PMID- 23532167
TI  - Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from
      substituted benzene substrates.
AB  - Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene
      substrates were used as precursors, in a chemoenzymatic synthesis of the
      corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene
      oxide intermediates. A rapid total racemization of the substituted benzene 2,3
      oxides was found to have occurred, via their oxepine valence tautomers, in accord
      with predictions and theoretical calculations. Reduction of a substituted arene
      oxide to yield a racemic arene hydrate was observed. Arene hydrates have also
      been synthesised, in enantiopure form, from the corresponding dihydroarene oxide
      or trans-bromoacetate precursors. Biotransformation of one arene hydrate
      enantiomer resulted in a toluene-dioxygenase catalysed cis-dihydroxylation to
      yield a benzene cis-triol metabolite.

PMID- 23532169
TI  - Evaluation of the impact of gonadotropin-releasing hormone agonist as an adjuvant
      in luteal-phase support on IVF outcome.
AB  - OBJECTIVES: To evaluate whether three daily doses of GnRH agonist (Inj. Lupride 1
      mg SC) administered 6 days after oocyte retrieval increases ongoing pregnancy
      rates following embryo transfer (ET) in cycles stimulated with the long GnRH
      agonist protocol. SETTINGS AND DESIGN: Prospective randomized controlled study in
      a tertiary care center. MATERIALS AND METHODS: Four hundred and twenty six women
      undergoing ET following controlled ovarian stimulation with a long GnRH agonist
      protocol were included. In addition to routine luteal-phase support (LPS) with
      progesterone, women were randomized to receive three 1 mg doses of Lupride 6 days
      after oocyte retrieval. Computer-generated randomization was done on the day of
      ET. Ongoing pregnancy rate beyond 20(th) week of gestation was the primary
      outcome measure. The trial was powered to detect a 13% absolute increase from an
      assumed 27% ongoing pregnancy rate in the control group, with an alpha error
      level of 0.05 and a beta error level of 0.2. RESULTS: There were 59 (27.69%)
      ongoing pregnancies in the GnRHa group, and 56 (26.29%) in the control group (P =
      0.827). Implantation, clinical pregnancy and multiple pregnancy rates were
      likewise similar in the GnRHa and placebo groups. CONCLUSIONS: Three 1 mg doses
      of Lupride administration 6 days after oocyte retrieval in the long protocol
      cycles does not result in an increase in ongoing pregnancy rates.

PMID- 23532170
TI  - Extent and distribution of CPP deposits in patients affected by calcium
      pyrophosphate dihydrate deposition disease: an ultrasonographic study.
AB  - OBJECTIVE: To assess the extent of calcium pyrophosphate dihydrate (CPP) crystal
      deposition and the distribution of affected sites, using ultrasonography (US), in
      patients affected by CPP deposition disease (CPPD). PATIENTS AND METHODS: 42
      consecutive patients affected by definite CPPD according to the McCarty criteria
      were enrolled in the study. All patients underwent an US examination of
      metacarpophalangeal joints of II, III, IV and V fingers of both hands, wrists and
      knees, Achilles' tendons and plantar fascia looking for CPP deposits. A
      dichotomous score for presence/absence of CPP and a semiquantitative score for
      extent of deposits (0-3: 0, absent; 1, 1-2 spots; 2, more than two spots covering
      <50% of the structure; 3, deposits covering >50% of the structure) were assigned
      to each site examined. A site distribution score (total number of affected sites)
      was then calculated as well as an extent score equal to the sum of the extent
      scores of all sites. RESULTS: The mean involvement in our patients was 4.7 sites
      (SD+/-1.7, range 2-8 sites). The knee was the most affected, site (41 of 42)
      followed by the wrist (at least one in 37 patients) the Achilles' tendons (23
      patients), plantar fascia (11 patients) and metacarpophalangeal joints (four
      patients). The highest mean values of the extent score were in the menisci,
      followed by the hyaline cartilage of the femoral condyles and the entheses.
      CONCLUSIONS: The deposition of CPP crystals involves at least two sites with a
      mean of four sites involved in most patients affected by CPPD and is therefore an
      oligoarticular or polyarticular disease.

PMID- 23532172
TI  - Ice-dependent winter survival of juvenile Atlantic salmon.
AB  - Changes in snow and ice conditions are some of the most distinctive impacts of
      global warming in cold temperate and Arctic regions, altering the environment
      during a critical period for survival for most animals. Laboratories studies have
      suggested that reduced ice cover may reduce the survival of stream dwelling
      fishes in Northern environments. This, however, has not been empirically
      investigated in natural populations in large rivers. Here, we examine how the
      winter survival of juvenile Atlantic salmon in a large natural river, the River
      Alta (Norway, 70 degrees N), is affected by the presence or absence of surface
      ice. Apparent survival rates for size classes corresponding to parr and presmolts
      were estimated using capture-mark-recapture and Cormack-Jolly-Seber models for an
      ice-covered and an ice-free site. Apparent survival (Phi) in the ice-covered site
      was greater than in the ice-free site, but did not depend on size class (0.64 for
      both parr and presmolt). In contrast, apparent survival in the ice-free site was
      lower for larger individuals (0.33) than smaller individuals (0.45). The over
      winter decline in storage energy was greater for the ice-free site than the ice
      covered site, suggesting that environmental conditions in the ice-free site
      caused a strong depletion in energy reserves likely affecting survival. Our
      findings highlight the importance of surface ice for the winter survival of
      juvenile fish, thus, underpinning that climate change, by reducing ice cover, may
      have a negative effect on the survival of fish adapted to ice-covered habitats
      during winter.

PMID- 23532171
TI  - HIRREMTM: a noninvasive, allostatic methodology for relaxation and auto
      calibration of neural oscillations.
AB  - Disturbances of neural oscillation patterns have been reported with many disease
      states. We introduce methodology for HIRREMTM (high-resolution, relational,
      resonance-based electroencephalic mirroring), also known as Brainwave
      OptimizationTM, a noninvasive technology to facilitate relaxation and auto
      calibration of neural oscillations. HIRREM is a precision-guided technology for
      allostatic therapeutics, intended to help the brain calibrate its own functional
      set points to optimize fitness. HIRREM technology collects electroencephalic data
      through two-channel recordings and delivers a series of audible musical tones in
      near real time. Choices of tone pitch and timing are made by mathematical
      algorithms, principally informed by the dominant frequency in successive instants
      of time, to permit resonance between neural oscillatory frequencies and the
      musical tones. Relaxation of neural oscillations through HIRREM appears to permit
      auto-calibration toward greater hemispheric symmetry and more optimized
      proportionation of regional spectral power. To illustrate an application of
      HIRREM, we present data from a randomized clinical trial of HIRREM as an
      intervention for insomnia (n = 19). On average, there was reduction of right
      dominant temporal lobe high-frequency (23-36 Hz) EEG asymmetry over the course of
      eight successive HIRREM sessions. There was a trend for correlation between
      reduction of right temporal lobe dominance and magnitude of insomnia symptom
      reduction. Disturbances of neural oscillation have implications for both
      neuropsychiatric health and downstream peripheral (somatic) physiology. The
      possibility of noninvasive optimization for neural oscillatory set points through
      HIRREM suggests potentially multitudinous roles for this technology. Research is
      currently ongoing to further explore its potential applications and mechanisms of
      action.

PMID- 23532173
TI  - Emergent bimodal firing patterns implement different encoding strategies during
      gamma-band oscillations.
AB  - Upon sensory stimulation, primary cortical areas readily engage in narrow-band
      rhythmic activity between 30 and 90 Hz, the so-called gamma oscillations. Here we
      show that, when embedded in a balanced network, type-I excitable neurons
      entrained to the collective rhythm show a discontinuity in their firing-rates
      between a slow and a fast spiking mode. This jump in the spiking frequencies is
      characteristic to type II neurons, but is not present in the frequency-current
      curve (f-I curve) of isolated type I neurons. Therefore, this rate bimodality
      arises as an emerging network property in type I population models. We have
      studied the mechanisms underlying the generation of these two firing modes, in
      order to reproduce the spiking activity of in vivo cortical recordings, which is
      known to be highly irregular and sparse. We have also analyzed the relation
      between afferent inputs and the single unit activity, and between the latter and
      the local field potential (LFP) phase, in order to establish how the collective
      dynamics modulates the spiking activity of the individual neurons. Our results
      reveal that the inhibitory-excitatory balance allows two encoding mechanisms, for
      input rate variations and LFP phase, to coexist within the network.

PMID- 23532175
TI  - EGFR signalling and oncogenic pathway signature in colorectal cancer.

PMID- 23532174
TI  - Stimulators of soluble guanylyl cyclase: future clinical indications.
AB  - BACKGROUND: Soluble guanylyl cyclase (sGC) is expressed in mammalian cytoplasm
      and catalyzes the synthesis of the second messenger guanosine 3',5'-monophosphate
      (cGMP) involved in important physiological functions such as relaxation of
      vascular smooth muscle, inhibition of platelet aggregation, modulation of
      inflammation, and control of vascular permeability. sGC is the intracellular
      receptor for nitric oxide (NO) and the active moiety in traditional organic
      nitrate therapy, recently as an inhalant in the intensive care unit and
      experimentally in improving microcirculatory flow in shock. However, dysfunction
      of the heme moiety on sGC occurs in a number of cardiovascular diseases, which
      reduces NO effectiveness. METHODS: In this review, we examine animal studies and
      early clinical trials on agents that can directly stimulate sGC and may have
      future clinical application in cardiovascular disease and in perioperative care.
      CONCLUSIONS: Animal and early clinical studies have shown that sGC stimulator
      agents have great promise for treating cardiopulmonary disorders and may also
      have a role in modulating the inflammatory response observed in perioperative
      care.

PMID- 23532177
TI  - Neonatal blood rheological parameters at delivery in healthy neonates and in
      those with morbidities.
AB  - Rheological blood parameters of neonates are different form those of adults. Many
      authors have studied changes in blood rheology in neonates in different clinical
      disorders. To-date, no one set the normal values for blood rheological parameters
      in healthy neonates. The aim of this study is to set the norm for rheological
      blood parameters in healthy newborns and to describe the changes in those
      parameters in common clinical disorders that affect the newborns. We recruited
      all the neonates born to mothers experiencing un eventful pregnancies, blood was
      taken from the umbilical cord right after the delivery. In this time period we
      recruited 4985 neonate. From this huge database we were able to set the standards
      for blood rheology in neonates, namely plasma viscosity of 1.06+/-0.072 mPa,
      erythrocyte aggregation at stasis of 2.41+/-2.74 s-1 and erythrocyte aggregation
      under low shear forces of 8.51+/-6.38 s-1. These values changed significantly in
      some diseased neonates. This is the largest study investigating normal
      rheological parameters and deviations from the norm in common clinical disorders
      occurring in this early stage of life.

PMID- 23532178
TI  - Design of synthetic genetic oscillators using evolutionary optimization.
AB  - Efforts have been made to establish computer models of genetic oscillation. We
      have developed a real structured genetic algorithm (RSGA) which combines
      advantages of the traditional real genetic algorithm (RGA) with those of the
      structured genetic algorithm (SGA) and applies it as an optimization strategy for
      genetic oscillator design. For the generalized design, our proposed approach
      fulfils all types of genes by minimizing the order of oscillator while searching
      for the optimal network parameters. The design approach is shown to be capable of
      yielding genetic oscillators with a simpler structure while possessing
      satisfactory oscillating behavior. In silico experiments show effectiveness of
      the proposed algorithm to genetic oscillator design. In particular, it is shown
      that the proposed approach performs better than the traditional GAs in the sense
      that a cheaper structure of genetic oscillators can be obtained.

PMID- 23532179
TI  - Synthesis, characterization and catalytic behavior toward ethylene of 2-[1-(4,6
      dimethyl-2-benzhydrylphenylimino)ethyl]-6-[1-(arylimino)ethyl]pyridylmetal (iron
      or cobalt) chlorides.
AB  - A series of 2-[1-(4,6-dimethyl-2-benzhydrylphenylimino)ethyl]-6-[1
      (arylimino)ethyl]pyridines was synthesized and used to prepare the iron(II) and
      cobalt(II) chloride complexes thereof. All organic compounds were fully
      characterized by elemental analysis, IR and NMR ((1)H/(13)C) spectroscopy, whilst
      the metal complexes were characterized by elemental analysis and IR spectroscopy
      as well as by single-crystal X-ray diffraction studies (for two representative
      cobalt complexes), which revealed that the geometry at the metal was either
      pseudo-square-pyramidal or trigonal bipyramidal. Upon activation with either
      methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), all metal complex
      pre-catalysts exhibited high activities for ethylene polymerization. The iron pre
      catalysts show much higher activity than did their cobalt analogues; however, the
      iron catalytic systems generally produced polyethylene of wide molecular weight
      polydispersity. At elevated reaction temperature, the polyethylene was of lower
      molecular weight, but revealed narrow polydispersity.

PMID- 23532180
TI  - Dosimetric evaluation of Acuros XB dose calculation algorithm with measurements
      in predicting doses beyond different air gap thickness for smaller and larger
      field sizes.
AB  - In this study, dose prediction accuracy of Acuros XB (AXB) dose calculation
      algorithm beyond air gap thickness (range 2, 4, and 6 cm) in simple inhomogeneous
      phantoms was investigated. The evaluation of AXB was performed by comparing the
      doses calculated by AXB with the doses calculated by Anisotropic Analytical
      Algorithm (AAA) and the measured data for different field sizes (3 * 3, 5 * 5,
      and 10 * 10 cm(2)) of a 6 MV photon beam. The dose computation was performed
      within Eclipse treatment planning system, and measurements were acquired with a
      cylindrical ionization chamber. Central axis depth dose comparisons were done in
      solid-water material region up to 5 cm distance from air/solid-water interface.
      The results of AXB had better agreement with measurements at all measured points
      than that of AAA. The discrepancies between AXB and measured data were seen from 
      3.81% to + 0.9%, whereas the AAA differences with measurement from - 3.1% to -
      10.9%. The combination of the smallest test field size and the largest air gap
      produced the highest range (1-5 cm distance from air/solid-water interface) in
      dose difference (AAA: -4.0% to - 10.6% and AXB: -3.8% to + 0.6%). The AAA
      computational time was about 8 times faster than that of AXB. In conclusion, AXB
      is more appropriate to use for dose predictions, especially when low-density
      heterogeneities are involved.

PMID- 23532176
TI  - The ATM signaling network in development and disease.
AB  - The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the
      appropriate cellular programs to maintain genome integrity. This includes the
      coordination of cell cycle checkpoints, transcription, translation, DNA repair,
      metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and
      Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most
      cytotoxic DNA lesions and defects in their metabolism underlie many human
      hereditary diseases characterized by genomic instability (Stracker and Petrini,
      2011; McKinnon, 2012). Patients with hereditary defects in the DDR display
      defects in development, particularly affecting the central nervous system, the
      immune system and the germline, as well as aberrant metabolic regulation and
      cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia
      mutated (ATM) kinase, a master controller of signal transduction. Understanding
      how ATM signaling regulates various aspects of the DDR and its roles in vivo is
      critical for our understanding of human disease, its diagnosis and its treatment.
      This review will describe the general roles of ATM signaling and highlight some
      recent advances that have shed light on the diverse roles of ATM and related
      proteins in human disease.

PMID- 23532181
TI  - Effectiveness of topical immunosuppressants in prevention and treatment of
      rejection in face allotransplantation.
AB  - BACKGROUND: The use of topical immunosuppressants has been anecdotally reported
      for the treatment of rejection in vascularized composite allotransplantation. The
      aim of this study was to evaluate the effectiveness of topical tacrolimus and
      clobetasol in the prevention and treatment of rejection. METHODS: Seventy-six
      hemiface allotransplants, between ACI (RT1) donors and Lewis (RT1) recipients,
      were performed in 11 groups and treated with topical tacrolimus or clobetasol, or
      in combination with systemic cyclosporine A and anti-alphabeta-T-cell receptor
      antibody for 1 week. Topical treatment increased the survival of the allograft in
      all groups. RESULTS: Best outcomes were obtained in the groups treated with
      systemic therapy and topical tacrolimus. Expression of proinflammatory cytokines
      interleukin 2, interferon gamma, tumor necrosis factor alpha, and transforming
      growth factor beta correlated with clinical signs of rejection and the final
      outcomes. Clobetasol application was associated with a marked depletion of
      lymphocytic populations, and dermal and epidermal atrophy. CONCLUSIONS: Both
      topical tacrolimus and clobetasol were effective in treating episodes of acute
      rejection, and the best outcomes were achieved when their application was
      initiated after systemic immunosuppression. Topical tacrolimus proved to be a
      preferable adjunct agent to the systemic therapy by preventing both the local and
      systemic complications.

PMID- 23532182
TI  - Dual fibular allograft dowel technique for sacroiliac joint arthrodesis.
AB  - STUDY DESIGN:  Retrospective case series. OBJECTIVE:  To assess fusion rates in
      patients with sacroiliac joint (SIJ) pain following a minimally invasive
      technique using fibular dowel allograft. METHODS:  Thirty-seven consecutive
      patients (mean age: 42.5 years [range, 23-63 years]) with SIJ pain treated with
      38 minimally invasive elective SIJ arthrodeses were retrospectively reviewed
      using chart and x-ray data. The fusion procedure consisted of minimal muscle
      stripping over the posterior SIJ and insertion of a cranial and caudal fibular
      dowel graft across the joint following placement of Steinmann pins. Fusion was
      deemed to be present when bone bridging trabeculae could be seen crossing the SIJ
      on either oblique x-rays or by computed tomographic scan. Patients were followed
      up for a mean of 52 months (range, 24-62 months). Visual Analog Scale (VAS) was
      used to monitor clinical pain improvement. RESULTS:  Thirty-four patients with
      SIJ arthrodeses (89.5%) healed and led to substantial improvement in VAS pain
      scores (preoperative 9.1, postoperative 3.4) (P < .001). This improvement in VAS
      occurred over a 6-month period and was sustained through subsequent follow-up.
      Nonunion occurred in four patients with SIJ (10.5%). Each SIJ nonunion was
      successfully treated by secondary autogenous bone grafting and compression screw
      fixation. CONCLUSIONS:  In patients with primary low back pain attributable to
      the SIJ, a minimally invasive, dual fibular dowel graft provided high rates of
      fusion and improved pain scores. [Table: see text].

PMID- 23532183
TI  - Rhodium(III)-catalyzed oxidative olefination of N-allyl sulfonamides.
AB  - Rhodium(III)-catalyzed oxidative couplings between N-sulfonyl allylamines and
      activated olefins have been achieved. Only olefination occurred for acrylates,
      and the butadiene product can be further cyclized under palladium-catalyzed
      aerobic conditions. The coupling with N,N-dimethylacrylamide followed a
      cyclization pathway.

PMID- 23532184
TI  - Conformational changes of beta-carotene and zeaxanthin immersed in a model
      membrane through atomistic molecular dynamics simulations.
AB  - In this work, we investigate systems formed by beta-carotene and zeaxanthin
      embedded separately in a model lipid bilayer of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) through molecular dynamics (MD) simulations. The study is
      conducted using an all-atoms model and by analyzing the structural changes that
      occur at both the carotenoid molecule and the membrane during the simulations. We
      concentrate specifically on the conformation of the conjugated chain, given the
      relevance that this feature has in modulating the spectroscopic and antioxidant
      properties of the carotenoids. The force fields of the carotenoids are
      parametrized accordingly in order to reproduce the rotation potentials of the
      conjugated chains calculated using quantum DFT methods. A model to quantify the
      effective conjugated chain length is presented. The MD simulations are carried
      out using the parameters adjusted for the carotenoids along with those provided
      by the CHARMM36 force field for the lipids of the membrane. A differentiating
      dynamic behavior of beta-carotene and zeaxanthin within the bilayer is observed
      in the simulations, which is analyzed in detail through umbrella sampling
      techniques. This behavior is driven basically by the interactions of the lipid
      polar heads with the hydroxyl groups of zeaxanthin, which are absent in beta
      carotene. These interactions influence the carotenoid orientation, modify the
      conformational distribution of the dihedral angles of the conjugated chain
      significantly, and specifically distort the membrane structure.

PMID- 23532185
TI  - The lipidome and proteome of oil bodies from Helianthus annuus (common
      sunflower).
AB  - In this paper we report the molecular profiling, lipidome and proteome, of the
      plant organelle known as an oil body (OB). The OB is remarkable in that it is
      able to perform its biological role (storage of triglycerides) whilst resisting
      the physical stresses caused by changes during desiccation (dehydration) and
      germination (rehydration). The molecular profile that confers such extraordinary
      physical stability on OBs was determined using a combination of (31)P/(1)H
      nuclear magnetic resonance (NMR), high-resolution mass spectrometry and nominal
      mass-tandem mass spectrometry for the lipidome, and gel-electrophoresis
      chromatography-tandem mass spectrometry for the proteome. The integrity of the
      procedure for isolating OBs was supported by physical evidence from small-angle
      neutron-scattering experiments. Suppression of lipase activity was crucial in
      determining the lipidome. There is conclusive evidence that the latter is
      dominated by phosphatidylcholine (~60 %) and phosphatidylinositol (~20 %), with a
      variety of other head groups (~20 %). The fatty acid profile of the surface
      monolayer comprised palmitic, linoleic and oleic acids (2:1:0.25, (1)H NMR) with
      only traces of other fatty acids (C24:0, C22:0, C18:0, C18:3, C16:2; by MS). The
      proteome is rich in oleosins (78 %) with the remainder being made up of caleosins
      and steroleosins. These data are sufficiently detailed to inform an update of the
      understood model of this organelle and can be used to inform the use of such
      components in a range of molecular biological, biotechnological and food industry
      applications. The techniques used in this study for profiling the lipidome throw
      a new light on the lipid profile of plant cellular compartments.

PMID- 23532186
TI  - A large cell neuroendocrine carcinoma of the gall bladder: diagnosis with 18FDG
      PET/CT-guided biliary cytology and treatment with combined chemotherapy achieved
      a long-term stable condition.
AB  - Poorly differentiated neuroendocrine cell carcinomas of the gallbladder are rare
      and patients with such tumors have a poor prognosis. We describe a 64-year-old
      male with a large cell neuroendocrine carcinoma of the gallbladder and multiple
      lymph node metastases. Diagnostic excisional biopsy of the left axillary lymph
      nodes revealed atypical cells with predominantly large-sized round-to-oval
      nuclei, proliferating in a solid and focal nesting pattern. The tumor cells were
      positive for synaptophysin and chromogranin A, and strongly positive for Ki-67,
      leading to a diagnosis of poorly differentiated neuroendocrine cell carcinoma of
      the gallbladder, of large cell type. Using (18)F-fluorodeoxy glucose-positron
      emission tomography/computed tomography to determine the origin of these tumors,
      we observed the accumulation of (18)F-fluorodeoxy glucose in multiple large lymph
      nodes, a small part of the liver and the fundus of the gallbladder. Computed
      tomography-guided aspiration of the gallbladder showed the same pleomorphic tumor
      cells as the lymph nodes. The patient was diagnosed with a large cell
      neuroendocrine carcinoma of the gallbladder, only ~25 mm in diameter. Combination
      chemotherapy with cisplatin and docetaxel, the regimen used for non-small cell
      lung carcinomas, and probably large cell lung carcinomas, resulted in the
      disappearance of the lymph node metastases and a marked improvement in the
      performance status for ~22 months. The poor prognosis of patients with these
      aggressive tumors may be improved by the use of minimally invasive diagnostic
      procedures and combined systemic chemotherapy as soon as possible.

PMID- 23532187
TI  - Serum albumin is an important prognostic factor for carotid blowout syndrome.
AB  - OBJECTIVE: Carotid blowout syndrome is a severe complication of head and neck
      cancer. High mortality and major neurologic morbidity are associated with carotid
      blowout syndrome with massive bleeding. Prediction of outcomes for carotid
      blowout syndrome patients is important for clinicians, especially for patients
      with the risk of massive bleeding. METHODS: Between 1 January 2001 and 31
      December 2011, 103 patients with carotid blowout syndrome were enrolled in this
      study. The patients were divided into groups with and without massive bleeding.
      Prognostic factors were analysed with proportional hazard (Cox) regressions for
      carotid blowout syndrome-related prognoses. Survival analyses were based on the
      time from diagnosis of carotid blowout syndrome to massive bleeding and death.
      RESULTS: Patients with massive bleeding were more likely to have hypoalbuminemia
      (albumin <3.5 g/dl; P = 0.023). Univariate analysis of carotid blowout syndrome
      related massive bleeding showed that treatment for carotid blowout syndrome (best
      supportive care, P = 0.000; embolization, P = 0.000), monocytosis (monocytes
      >1000 cells/MUl, P = 0.041) and hypoalbuminemia (P = 0.010) were important to
      prognosis. Concurrent chemoradiotherapy (P = 0.007), elevated lactate
      dehydrogenase (>250 U/l; P = 0.050), local recurrence (P = 0.022) and
      hypoalbuminemia (P = 0.038) were related to poor prognosis in carotid blowout
      syndrome-related death. In multivariate analysis, best supportive care and
      hypoalbuminemia were independent factors for both carotid blowout syndrome
      related massive bleeding (P = 0.000) and carotid blowout syndrome-related death
      (P = 0.013), respectively. CONCLUSION: Best supportive care and serum albumin are
      important prognostic factors in carotid blowout syndrome. It helps clinicians to
      evaluate and provide better supportive care for these patients.

PMID- 23532188
TI  - Effects of integrated psychosocial care for distress in cancer patients.
AB  - BACKGROUND: Despite some clinical guidelines for incorporating integrated
      psychosocial care (combining psychological screening and psychological
      intervention, including adequate collaboration with mental health specialists)
      into routine oncology practice, definitive empirical evidence regarding the
      effectiveness of such care remains unavailable. Here the findings of recent
      experimental studies are reviewed to provide guidance regarding this issue.
      METHODS: Comparative studies examining integrated psychosocial care were
      reviewed. RESULTS: Studies examining interventions that include both screening
      and psychological care have produced contradictory results regarding
      effectiveness, but all the studies that have examined the effect of psychological
      care after the identification of distress using systematic screening have shown
      positive results. CONCLUSIONS: Integrated psychosocial care may affect patients
      with significant distress, but the adequacy of introducing such care into routine
      oncology practice remains debatable.

PMID- 23532189
TI  - Midterm results of cruciate retaining total knee arthroplasty in patellectomized
      patients.
AB  - BACKGROUND: Total knee arthroplasty (TKA) in patellectomized patients gives
      inferior results when compared with those in which the patella is present. The
      literature is ambiguous about the role of cruciate retaining or sacrificing
      implants for these knees. In this study, we assessed the midterm results of TKA
      in patellectomized knees using a cruciate retaining implant. MATERIALS AND
      METHODS: Thirty three patients with a prior patellectomy underwent a cruciate
      retaining TKA and were followed up for an average of 9.3 years (range 2-14
      years). At each followup visit, they were evaluated clinically, radiologically
      and by the Hospital for Special Surgery Scoring System. RESULTS: Twenty one knees
      did not have any pain or difficulty in climbing stairs, 10 knees were slightly
      painful on stairs but pain free on walking on flat ground and two knees
      experienced mild to moderate pain on walking up and down stairs as well as on
      flat ground. The average range of motion preoperatively was 87 degrees , which
      postoperatively increased to 118 degrees . The average Hospital for Special
      Surgery Knee scores increased from 52 to 89 points. None of the knees showed any
      progressive radiolucencies or evidence of any loosening/osteolysis or fractures
      in followup. CONCLUSION: Cruciate retaining TKA offers good results at midterm
      followup in patients with a prior patellectomy.

PMID- 23532190
TI  - Noise sensitivity and disability retirement: a longitudinal twin study.
AB  - OBJECTIVE: To analyze whether noise sensitivity increases the risk of disability
      pension (DP). METHODS: Questionnaire data of a sample of 706 Finnish twin
      individuals (age range, 31 to 65 years) with record linkage to information on DP
      during 16 years of follow-up were analyzed using individual and pairwise Cox
      proportional hazards models. RESULTS: Noise sensitivity increased the risk of DP
      (hazard ratio = 1.41; 95% confidence interval [CI]: 1.03 to 1.93) and DP due to
      musculoskeletal disorders (hazard ratio = 1.63; 95% CI: 1.00 to 2.66). In within
      pair analyses, noise sensitivity increased the risk of DP: among all twin pairs,
      odds ratio was 1.80 (95% CI: 1.08 to 3.06). CONCLUSIONS: Noise sensitivity may be
      a potential risk factor for disability retirement. It is associated with DP
      independently of familial background and genetic factors.

PMID- 23532191
TI  - The associations between organizational social capital, perceived health, and
      employees' performance in two Dutch companies.
AB  - OBJECTIVE: To examine the associations between organizational (bonding, bridging,
      and linking) social capital, employees' health, and employees' performance.
      METHODS: Linear regression on cross-sectional data among 718 employees in two
      Dutch companies. RESULTS: Organizational social capital was significantly
      associated with perceived health (beta = 0.20; P < 0.001) and with emotional
      exhaustion (beta = -0.34; P < 0.001). Both the health indicators, in turn, were
      associated with absenteeism, presenteeism, and effective personal functioning in
      the presumed direction, that is, better health was associated with better
      functioning. Especially, bonding social capital was significantly associated with
      health (beta = 0.14; P < 0.01) and with emotional exhaustion (beta = -0.26; P <
      0.001). Linking social capital was associated with emotional exhaustion as well
      (beta = -0.09; P < 0.05). CONCLUSIONS: Organizational social capital was found to
      be a resource for employees' health, with meaningful business implications.

PMID- 23532192
TI  - Analyzing best practices in employee health management: how age, sex, and program
      components relate to employee engagement and health outcomes.
AB  - OBJECTIVE: Examine the influence of employee health management (EHM) best
      practices on registration, participation, and health behavior change in telephone
      based coaching programs. METHODS: Individual health assessment data, EHM program
      data, and health coaching participation data were analyzed for associations with
      coaching program enrollment, active participation, and risk reduction.
      Multivariate analyses occurred at the individual (n = 205,672) and company levels
      (n = 55). RESULTS: Considerable differences were found in how age and sex
      impacted typical EHM evaluation metrics. Cash incentives for the health
      assessment were associated with more risk reduction for men than for women.
      Providing either a noncash or a benefits-integrated incentive for completing the
      health assessment, or a noncash incentive for lifestyle management, strengthened
      the relationship between age and risk reduction. CONCLUSIONS: In EHM programs,
      one size does not fit all. These results can help employers tailor engagement
      strategies for their specific population.

PMID- 23532193
TI  - Health risk factor modification predicts incidence of diabetes in an employee
      population: results of an 8-year longitudinal cohort study.
AB  - OBJECTIVE: To understand risk factor modification effect on Type 2 diabetes
      incidence in a workforce population. METHODS: Annual health risk assessment data
      (N = 3125) in years 1 through 4 were used to predict diabetes development in
      years 5 through 8. RESULTS: Employees who reduced their body mass index from 30
      or more to less than 30 decreased their chances of developing diabetes (odds
      ratio = 0.22, 95% confidence interval: 0.05 to 0.93), while those who became
      obese increased their diabetes risk (odds ratio = 8.85, 95% confidence interval:
      2.53 to 31.0). CONCLUSIONS: Weight reduction observed over a long period can
      result in clinically important reductions in diabetes incidence. Workplace health
      promotion programs may prevent diabetes among workers by encouraging weight loss
      and adoption of healthy lifestyle habits.

PMID- 23532194
TI  - Excessive daytime sleepiness in firefighters in the central United States.
AB  - OBJECTIVE: To determine the prevalence and severity of excessive daytime
      sleepiness (EDS) in a population-based sample of firefighters. METHODS:
      Sleepiness was assessed using the Epworth Sleepiness Scale in a sample of male
      career firefighters (n = 458) from 11 randomly selected fire departments in the
      Midwestern United States. RESULTS: Unadjusted EDS rates (13.7% and 14.0% for on-
      and off-duty, respectively) were similar to the general US population and
      comparable occupational groups. Factors associated with EDS included 48-hour work
      shifts, non-private department sleep areas, and working a second job outside the
      fire service (P < 0.05). CONCLUSION: Given firefighters' important role in public
      safety, concerns have been raised about whether firefighters' work schedules
      result in high rates of excessive sleepiness. Nevertheless, firefighters in this
      study did not have high rates of EDS despite their extended work schedule.

PMID- 23532195
TI  - Postural sway and exposure to jet propulsion fuel 8 among US Air Force personnel.
AB  - OBJECTIVE: To determine whether short-term jet propulsion fuel 8 (JP-8) exposure
      is associated with balance measurements in JP-8-exposed air force personnel.
      METHODS: As part of a larger neuroepidemiology study, balance tasks were
      completed by JP-8-exposed individuals (n = 37). Short-term JP-8 exposure was
      measured using personal breathing zone levels and urinary biomarkers.
      Multivariate linear regression analyses were conducted to examine the
      relationship between workday JP-8 exposure and postural sway. RESULTS: Balance
      control decreased as the task became more challenging. Workday exposure to JP-8,
      measured by either personal air or urinary metabolite levels, was not
      significantly related to postural sway. Increases in workday postural sway were
      associated with demographic variables, including younger age, being a current
      smoker, and higher body mass index. CONCLUSION: Results suggest that short-term
      workday JP-8 exposure does not significantly contribute to diminished balance
      control.

PMID- 23532196
TI  - Effort-reward imbalance at work and risk of long-term sickness absence in the
      Danish workforce.
AB  - OBJECTIVE: To examine whether effort-reward imbalance (ERI) at work predicts
      onset of register-based long-term sickness absence (LTSA) in a representative
      sample of the Danish workforce. METHODS: We measured effort, reward, ERI, and
      covariates with self-administered questionnaires in a sample of 4775 employees.
      LTSA during 12-months of follow-up was assessed with a national register. We
      calculated hazard ratios (HRs) with Cox proportional hazard models. RESULTS: The
      HR of LTSA for a one-SD increase in ERI was 1.03 (95% confidence interval [CI],
      0.93-1.15) in the most-adjusted model. For effort, the HR for a one-SD increase
      was 0.95 (95% CI, 0.85-1.06) and for reward the HR for a one-SD decrease was 1.14
      (95% CI, 1.03-1.26). CONCLUSIONS: ERI was not associated with onset of LTSA. Low
      reward, however, predicted LTSA.

PMID- 23532197
TI  - Influence of new secondary diagnoses on the duration of non-work-related sickness
      absence episodes.
AB  - OBJECTIVE: To describe the frequency and distribution of new diagnoses
      (codiagnoses) arising during a sickness absence (SA) episode, and to analyze
      their effect on duration of non-work-related SA in Spain. METHODS: Prospective
      cohort study from 2004 to 2007. Overall, 15,246 episodes occurred in a population
      base of 632,000 workers. Median duration of the episodes was the measured
      outcome. A Cox survival analysis, stratified by sex, estimated the hazard ratio
      to case closure adjusting by initial diagnosis, codiagnoses, demographic, and
      employment-related variables. RESULTS: The effect of an increasing number of
      codiagnoses on duration of the SA episode was evidenced by a progressively
      decreasing hazard ratio. This was present in both sexes, although the effect was
      greater in men. CONCLUSIONS: New conditions arising in the course of a SA episode
      significantly prolong its duration.

PMID- 23532198
TI  - Direct and indirect costs of women diagnosed with menopause symptoms.
AB  - OBJECTIVE: To quantify employee burden of those diagnosed with menopause
      symptoms. METHODS: This regression-based study analyzed 2001-to-2010 medical,
      pharmacy, sick leave, disability, workers' compensation, and productivity data of
      large US employers. A cohort of employed women with diagnosed menopause symptoms
      (DMS), aged more than 40 years, were identified using medical claims
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes 627.xx. Control employees were propensity matched on age, employer, plan
      enrollment length, and enrollment end date. RESULTS: The study included 17,322 in
      each cohort. Employees with DMS had significantly higher medical ($4315 vs $2972,
      P < 0.001), pharmacy ($1366 vs $908, P < 0.001), sick leave costs ($647 vs $599,
      P < 0.001), and sick leave days (3.57 vs 3.30, P < 0.001). Employees with DMS had
      12.2% (P = 0.007) lower hourly productivity and 10.9% (P = 0.014) lower annual
      productivity than controls. CONCLUSIONS: Although all women experience menopause,
      women with DMS have significantly higher utilization and productivity burdens.

PMID- 23532200
TI  - Addressing the competitive formation of tandem DNA lesions by a nucleobase
      peroxyl radical: a DFT-D screening.
AB  - The presence of two vicinal single-nucleotide oxidative lesions constitutes a
      pitfall case for DNA repair. Quantum mechanics calculations are performed to
      elucidate the formation of peroxyl-bridged adducts, where a purine and a
      pyrimidine base become covalently tethered. A dispersion-corrected density
      functional theory (DFT-D) screening along the 32 possible adducts built by a
      combination of the four different nucleobases outlines that guanine is a better
      tandem partner than adenine, in line with experimental data. In contrast,
      cytosine and thymine have an overall comparable reactivity as revealed by a
      highly localized spin density. For a given purine and pyrimidine combination, our
      computational approach also sketches some differences concerning the syn vs. anti
      configurations and the orientation strand.

PMID- 23532201
TI  - [Use and interpretation of the number needed to treat in urological practice].
AB  - The number needed to treat (NNT) is a useful way for clinicans to describe the
      benefit or harm of a treatment as well as the costs involved. When interpreting
      the NNT it is essential to use the NNT in a clinically equivalent and appropriate
      setting. When evaluating the consequences of a treatment clinicians should make
      sure that the patients being treated have the same risk profile asthe study
      patients. Differences in duration of follow-up and baseline risks can cause
      significant changes in the NNT; therefore, NNT should be evaluated in addition to
      relative risk differences and baseline risk to reduce any ambivalence in the
      assessment of a treatment. This review provides insights into the assessment and
      clinical use of NNT in the practice.

PMID- 23532202
TI  - Specialist valve clinics: recommendations from the British Heart Valve Society
      working group on improving quality in the delivery of care for patients with
      heart valve disease.

PMID- 23532203
TI  - Epileptic neuronal networks: methods of identification and clinical relevance.
AB  - The main objective of this paper is to examine evidence for the concept that
      epileptic activity should be envisaged in terms of functional connectivity and
      dynamics of neuronal networks. Basic concepts regarding structure and dynamics of
      neuronal networks are briefly described. Particular attention is given to
      approaches that are derived, or related, to the concept of causality, as
      formulated by Granger. Linear and non-linear methodologies aiming at
      characterizing the dynamics of neuronal networks applied to EEG/MEG and combined
      EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional
      dynamical analysis of neuronal networks with respect to clinical queries in focal
      cortical dysplasias, temporal lobe epilepsies, and "generalized" epilepsies is
      emphasized. In the light of the concepts of epileptic neuronal networks, and
      recent experimental findings, the dichotomic classification in focal and
      generalized epilepsy is re-evaluated. It is proposed that so-called "generalized
      epilepsies," such as absence seizures, are actually fast spreading epilepsies,
      the onset of which can be tracked down to particular neuronal networks using
      appropriate network analysis. Finally new approaches to delineate epileptogenic
      networks are discussed.

PMID- 23532204
TI  - Dualities in the analysis of phage DNA packaging motors.
AB  - The DNA packaging motors of double-stranded DNA phages are models for analysis of
      all multi-molecular motors and for analysis of several fundamental aspects of
      biology, including early evolution, relationship of in vivo to in vitro
      biochemistry and targets for anti-virals. Work on phage DNA packaging motors both
      has produced and is producing dualities in the interpretation of data obtained by
      use of both traditional techniques and the more recently developed procedures of
      single-molecule analysis. The dualities include (1) reductive vs. accretive
      evolution, (2) rotation vs. stasis of sub-assemblies of the motor, (3) thermal
      ratcheting vs. power stroking in generating force, (4) complete motor vs. spark
      plug role for the packaging ATPase, (5) use of previously isolated vs. new
      intermediates for analysis of the intermediate states of the motor and (6) a
      motor with one cycle vs. a motor with two cycles. We provide background for these
      dualities, some of which are under-emphasized in the literature. We suggest
      directions for future research.

PMID- 23532206
TI  - Phase II study of pemetrexed as first-line treatment in elderly (>=75) non
      squamous non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial
      0901.
AB  - BACKGROUND: Single-agent chemotherapy with third-generation non-platinum agents,
      such as docetaxel, vinorelbine, is a standard therapeutic option for elderly
      patients with non-small-cell lung cancer (NSCLC). Subset analysis of a previous
      phase III study comparing pemetrexed with docetaxel in the second-line setting
      showed the superiority of pemetrexed in an elderly (>=70) population in both
      efficacy and toxicity. PATIENTS AND METHODS: This was a single-arm phase II study
      of pemetrexed in elderly (>=75) Japanese patients with advanced non-squamous
      NSCLC. Patients received four cycles of pemetrexed (500 mg/m(2)) every 3 weeks.
      The primary endpoint was the response rate, and secondary endpoints were safety
      and survival. RESULTS: Twenty-eight patients were enrolled between January 2010
      and April 2012. The median age of the patients was 77 years (range 75-88). All
      but one patient had adenocarcinoma histology. The median number of chemotherapy
      cycles administered was 4 (range, 1-12). Seventeen (60 %) patients completed four
      cycles of chemotherapy. Partial response was achieved in 7 patients (response
      rate: 25 %) and stable disease in 11 patients (disease control rate: 64 %).
      Median progression-free survival and overall survival were 3.3 and 17.5 months,
      respectively. Grade 3/4 neutropenia and thrombocytopenia were observed in 8
      patients (29 %) and 2 (7 %), respectively. Non-hematologic toxicities were
      generally mild, and there were no treatment-related deaths. CONCLUSIONS: Although
      this study did not meet our primary endpoint, pemetrexed showed favorable
      antitumor activity with mild toxicity in elderly patients with non-squamous
      NSCLC. Further investigations of pemetrexed in this population are warranted
      (UMIN-CTR number, 000002452).

PMID- 23532207
TI  - Toxicity study of gemcitabine, oxaliplatin, and bevacizumab, followed by 5
      fluorouracil, oxaliplatin, bevacizumab, and radiotherapy, in patients with
      locally advanced pancreatic cancer.
AB  - PURPOSE: Platinum compounds or bevacizumab, in combination with gemcitabine,
      achieved good response rates in early studies in advanced pancreatic cancer. This
      prompted an evaluation of an aggressive approach to allow better local control
      and resectability in locally advanced disease. METHODS: We piloted a combination
      of gemcitabine/oxaliplatin/bevacizumab Q2w for four cycles, followed by
      oxaliplatin and bevacizumab added to infusional 5-FU and radiotherapy, in
      patients with locally advanced pancreatic cancer. RESULTS: Nineteen patients were
      treated, of whom 17 completed the protocol-specified treatment. Median age was 60
      years. Fifteen had unresectable, and four had borderline resectable disease.
      Toxicity of chemotherapy was moderate: grade III neutropenia (5) and grade I/II
      nausea, vomiting, fatigue, and neuropathy. During chemoradiation, major grade III
      toxicities were nausea and vomiting (3 each). One patient had intractable pain
      early on, necessitating treatment cessation. Response rate for 18 evaluable
      patients was 11 % (by RECIST); five patients (4 inoperable, 1 borderline, 26 %)
      went on to have surgery. One-year overall survival was 58 % and progression-free
      survival was 37 %. CONCLUSIONS: This combination, associated with higher response
      rates in metastatic disease, had a lower than expected response rate in primary
      tumors. Although tolerable, our approach failed to affect clinical outcomes
      meaningfully.

PMID- 23532205
TI  - Embodiment and sense-making in autism.
AB  - In this article, I sketch an enactive account of autism. For the enactive
      approach to cognition, embodiment, experience, and social interaction are
      fundamental to understanding mind and subjectivity. Enaction defines cognition as
      sense-making: the way cognitive agents meaningfully connect with their world,
      based on their needs and goals as self-organizing, self-maintaining, embodied
      agents. In the social realm, the interactive coordination of embodied sense
      making activities with others lets us participate in each other's sense-making
      (social understanding = participatory sense-making). The enactive approach
      provides new concepts to overcome the problems of traditional functionalist
      accounts of autism, which can only give a piecemeal and disintegrated view
      because they consider cognition, communication, and perception separately, do not
      take embodied into account, and are methodologically individualistic. Applying
      the concepts of enaction to autism, I show: How embodiment and sense-making
      connect, i.e., how autistic particularities of moving, perceiving, and emoting
      relate to how people with autism make sense of their world. For instance,
      restricted interests or preference for detail will have certain sensorimotor
      correlates, as well as specific meaning for autistic people.That reduced
      flexibility in interactional coordination correlates with difficulties in
      participatory sense-making. At the same time, seemingly irrelevant "autistic
      behaviors" can be quite attuned to the interactive context. I illustrate this
      complexity in the case of echolalia. An enactive account of autism starts from
      the embodiment, experience, and social interactions of autistic people. Enaction
      brings together the sensorimotor, cognitive, social, experiential, and affective
      aspects of autism in a coherent framework based on a complex non-linear multi
      causality. This foundation allows to build new bridges between autistic people
      and their often non-autistic context, and to improve quality of life prospects.

PMID- 23532208
TI  - Efficacy of bevacizumab-containing chemotherapy for non-squamous non-small cell
      lung cancer with bone metastases.
AB  - PURPOSE: Skeletal-related events (SREs) negatively affect the quality of life of
      patients with cancer. Vascular endothelial growth factor receptor (VEGFR)
      targeted therapy is effective against bone metastasis in animal models, but the
      clinical efficacy of anti-VEGFR inhibitors against bone metastases remains
      unclear. Therefore, we aimed to investigate the efficacy of chemotherapy with
      bevacizumab, an anti-VEGF antibody, against bone metastases. METHODS: We
      retrospectively reviewed consecutive patients with non-squamous non-small cell
      lung cancer who received first-line platinum-based chemotherapy with zoledronic
      acid at Shizuoka Cancer Center between 2007 and 2011. RESULTS: Of 25 patients, 13
      received bevacizumab-based chemotherapy (BEV group) and 12 received chemotherapy
      without bevacizumab (non-BEV group). The overall response (54 vs. 8 %, p = 0.01)
      and disease control (100 vs. 50 %, p = 0.01) rates were higher in the BEV group
      than in the non-BEV group. The bone-specific response (23 vs. 0 %, p = 0.038) and
      disease control (100 vs. 67 %, p = 0.01) rates were also higher in the BEV group.
      The median time to progression (TTP) for bone metastases was higher in the BEV
      group (13.7 vs. 4.3 months, p = 0.06), whereas that for overall disease was
      similar between the groups (5.7 vs. 2.6 months, p = 0.17). The proportions of
      patients with SREs were 23 and 50 % in the BEV and non-BEV groups, respectively
      (p = 0.16). CONCLUSION: Bevacizumab might potentiate the antitumor activity of
      chemotherapy against systemic disease and bone metastases, prolonging bone
      specific TTP and reducing the incidence of SRE.

PMID- 23532210
TI  - A selective turn-on fluorescent probe for Cd2+ based on a boron difluoride beta
      dibenzoyl dye and its application in living cells.
AB  - Herein we report the first example of a difluoroboron dibenzoyl based fluorescent
      probe for Cd(2+) detection. The probe displays high selectivity and sensitivity
      toward Cd(2+) over Zn(2+) in aqueous solution under physiological conditions.
      Fluorescence imaging experiments demonstrate its potential application for
      detecting Cd(2+) in living cells.

PMID- 23532212
TI  - Enzymatic saccharification of shrub willow genotypes with differing biomass
      composition for biofuel production.
AB  - In the conversion of woody biomass feedstocks into liquid fuel ethanol, the
      pretreatment process is the most critical and costly step. Variations in biomass
      composition based on genetic differences or environmental effects have a
      significant impact on the degree of accessibility accomplished by pretreatment
      and subsequent sugar release by enzymatic hydrolysis. To evaluate this, biomass
      from 10 genetically diverse, genotypes of shrub willow (Salix spp.) was
      pretreated with a hot-water process at two levels of severity, hydrolyzed using a
      combination of two commercial enzyme cocktails, and the release of hexose and
      pentose monomers was quantified by high-performance liquid chromatography. Among
      the genotypes selected for analysis, cellulose content ranged from 39 to 45%
      (w/w) and lignin content ranged from 20 to 23% (w/w) at harvest. Differences in
      the effectiveness of the pretreatment process were observed among the various
      willow genotypes. Correlations were identified between total sugar release and %
      cellulose and % lignin content. There was a significant effect of pretreatment
      severity on polysaccharide accessibility, but the response to pretreatments was
      different among the genotypes. At the high severity pretreatment 'SV1' was the
      least recalcitrant with sugar release representing as much as 60% of total
      biomass. These results suggest that structural, as well as chemical
      characteristics of the biomass may influence pretreatment and hydrolytic
      efficiency.

PMID- 23532211
TI  - Do multiple nuclear factor kappa B activation mechanisms explain its varied
      effects in the heart?
AB  - BACKGROUND: Multiple studies have demonstrated the important role of the nuclear
      factor kappa B (NF-kappaB) in cardiac pathology. However, these studies'
      conclusions differ regarding whether NF-kappaB is protective or detrimental for
      heart function. This disagreement is not surprising considering the complexity of
      NF-kappaB signaling that involves multiple components and regulation at several
      steps. Furthermore, NF-kappaB is a pleiotropic transcription factor that receives
      signals from multiple pathways, including the renin-angiotensin system (RAS) and
      cytokines, 2 important modulators of cardiac remodeling. METHODS: In this
      article, we review studies related to the role and mechanisms of NF-kappaB
      activation in the heart, particularly with regard to the RAS, inflammation, and
      diabetes. The objective of this review is to consolidate multiple, often
      contradictory, findings to develop a clear understanding of NF-kappaB signaling
      in the heart. CONCLUSIONS: The studies we review demonstrate that NF-kappaB
      effects in the heart are mechanism specific and that NF-kappaB signaling is
      cyclical. Consequently, the timing of NF-kappaB measurement is critical, and
      studies focused on temporal changes in the NF-kappaB mechanism would help clarify
      its multiple roles in cardiac pathophysiology.

PMID- 23532213
TI  - Personalised treatment of haematological malignancies through systems medicine
      based on single molecules in single cells.
AB  - Molecular diagnostics in haematological malignancies continues to advance towards
      more personalized treatment and accordingly demand is increasing for procedures
      providing quantitative analyses of heterogeneous tissue in malignancies.
      Circulating leukaemic cells are diverse and comprise discrete clonal populations
      arising from a common progenitor cell. Some of the current diagnostic techniques
      possess an attenuated dynamic quantitative range that prevents a clear
      comprehension of intercellular interactions. Quantitative measurements will
      facilitate an accurate appreciation of holistic cellular processes, assist with
      predictions pertaining to perturbations and reveal functional moieties that are
      truly a facet of the disease, and thus add to current biomarker discovery which
      often lack assessment of functional involvement in disease mechanisms and
      processes. This review focuses on quantitative studies related to peripheral
      blood and haematological malignancies. Data retrieval for either of these
      diseases is hampered by the high and unchartered degree of heterogeneity
      typically existing within clinical samples. The likelihood of analysis across
      single cell populations is highly probable in the near future. This will allow a
      patient to be readily screened for malignancies and assigned to a risk group
      based on a quantitative profile of a complex of molecules related to disease. The
      future analysis of molecular pathology based on detailed molecular dissection
      looks promising, requiring the integration of various disciplines encompassing
      morphology, genetics, expression profiling and new and evolving predictive
      modeling via systems medicine. From this detailed view into patient health, an
      increasingly personalized treatment plan can be administered, commencing with
      stratified medicine.

PMID- 23532216
TI  - The cover. Easter sunday.

PMID- 23532218
TI  - The rattlesnake-venom treatment of epilepsy.

PMID- 23532219
TI  - After 50 years, newborn screening continues to yield public health gains.

PMID- 23532220
TI  - Studies probe restoring speech in persons with chronic stroke-related aphasia.

PMID- 23532228
TI  - Warfarin treatment after bioprosthetic aortic valve replacement.

PMID- 23532229
TI  - Warfarin treatment after bioprosthetic aortic valve replacement--reply.

PMID- 23532230
TI  - Aspirin use and risk of macular degeneration.

PMID- 23532231
TI  - Aspirin use and risk of macular degeneration.

PMID- 23532232
TI  - Aspirin use and risk of macular degeneration--reply.

PMID- 23532233
TI  - Funding for biomedical research.

PMID- 23532234
TI  - Funding for biomedical research--reply.

PMID- 23532238
TI  - The economics of genomic medicine: insights from the IOM Roundtable on
      Translating Genomic-Based Research for Health.

PMID- 23532239
TI  - A piece of my mind. The NRA let me down.

PMID- 23532241
TI  - Effect of azithromycin maintenance treatment on infectious exacerbations among
      patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled
      trial.
AB  - IMPORTANCE: Macrolide antibiotics have been shown beneficial in cystic fibrosis
      (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in
      non-CF bronchiectasis. OBJECTIVE: To determine the efficacy of macrolide
      maintenance treatment for adults with non-CF bronchiectasis. DESIGN, SETTING, AND
      PARTICIPANTS: The BAT (Bronchiectasis and Long-term Azithromycin Treatment)
      study, a randomized, double-blind, placebo-controlled trial conducted between
      April 2008 and September 2010 in 14 hospitals in The Netherlands among 83
      outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract
      infections in the preceding year. INTERVENTIONS: Azithromycin (250 mg daily) or
      placebo for 12 months. MAIN OUTCOME MEASURES: Number of infectious exacerbations
      during 12 months of treatment. Secondary end points included lung function,
      sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and
      quality of life. RESULTS: Forty-three participants (52%) received azithromycin
      and 40 (48%) received placebo and were included in the modified intention-to
      treat analysis. At end of study, the median number of exacerbations in the
      azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR,
      1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20
      (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio,
      0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory
      volume in the first second of expiration (percent of predicted) over time
      differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03%
      per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in
      the placebo group. Gastrointestinal adverse effects occurred in 40% of patients
      in the azithromycin group and in 5% in the placebo group (relative risk, 7.44
      [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for
      diarrhea) but without need for discontinuation of study treatment. A macrolide
      resistance rate of 88% was noted in azithromycin-treated individuals, compared
      with 26% in the placebo group. CONCLUSIONS AND RELEVANCE: Among adults with non
      CF bronchiectasis, the daily use of azithromycin for 12 months compared with
      placebo resulted in a lower rate of infectious exacerbations. This could result
      in better quality of life and might influence survival, although effects on
      antibiotic resistance need to be considered. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00415350.

PMID- 23532242
TI  - Effect of long-term, low-dose erythromycin on pulmonary exacerbations among
      patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled
      trial.
AB  - IMPORTANCE: Macrolide antibiotics such as erythromycin may improve clinical
      outcomes in non-cystic fibrosis (CF) bronchiectasis, although associated risks of
      macrolide resistance are poorly defined. OBJECTIVE: To evaluate the clinical
      efficacy and antimicrobial resistance cost of low-dose erythromycin given for 12
      months to patients with non-CF bronchiectasis with a history of frequent
      pulmonary exacerbations. DESIGN, SETTING, AND PARTICIPANTS: Twelve-month,
      randomized (1:1), double-blind, placebo-controlled trial of erythromycin in
      currently nonsmoking, adult patients with non-CF bronchiectasis with a history of
      2 or more infective exacerbations in the preceding year. This Australian study
      was undertaken between October 2008 and December 2011 in a university teaching
      hospital, with participants also recruited via respiratory physicians at other
      centers and from public radio advertisements. INTERVENTIONS: Twice-daily
      erythromycin ethylsuccinate (400 mg) or matching placebo. MAIN OUTCOME MEASURES:
      The primary outcome was the annualized mean rate of protocol-defined pulmonary
      exacerbations (PDPEs) per patient. Secondary outcomes included macrolide
      resistance in commensal oropharyngeal streptococci and lung function. RESULTS:
      Six-hundred seventy-nine patients were screened, 117 were randomized (58 placebo,
      59 erythromycin), and 107 (91.5%) completed the study. Erythromycin significantly
      reduced PDPEs both overall (mean, 1.29 [95% CI, 0.93-1.65] vs 1.97 [95% CI, 1.45
      2.48] per patient per year; incidence rate ratio [IRR], 0.57 [95% CI, 0.42-0.77];
      P = .003), and in the prespecified subgroup with baseline Pseudomonas aeruginosa
      airway infection (mean difference, 1.32 [95% CI, 0.19-2.46]; P = .02).
      Erythromycin reduced 24-hour sputum production (median difference, 4.3 g
      [interquartile range [IQR], 1 to 7.8], P = .01) and attenuated lung function
      decline (mean absolute difference for change in postbronchodilator forced
      expiratory volume in the first second of expiration, 2.2 percent predicted [95%
      CI, 0.1% to 4.3%]; P = .04) compared with placebo. Erythromycin increased the
      proportion of macrolide-resistant oropharyngeal streptococci (median change,
      27.7% [IQR, 0.04% to 41.1%] vs 0.04% [IQR, -1.6% to 1.5%]; difference, 25.5%
      [IQR,15.0% to 33.7%]; P < .001). CONCLUSION AND RELEVANCE: Among patients with
      non-CF bronchiectasis, the 12-month use of erythromycin compared with placebo
      resulted in a modest decrease in the rate of pulmonary exacerbations and an
      increased rate of macrolide resistance. TRIAL REGISTRATION: anzctr.org.au
      Identifier: ACTRN12609000578202.

PMID- 23532243
TI  - Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and
      asthma: a systematic review.
AB  - IMPORTANCE: Allergic rhinitis affects up to 40% of the US population. To
      desensitize allergic individuals, subcutaneous injection immunotherapy or
      sublingual immunotherapy may be administered. In the United States, sublingual
      immunotherapy is not approved by the Food and Drug Administration. However, some
      US physicians use aqueous allergens, off-label, for sublingual desensitization.
      OBJECTIVE: To systematically review the effectiveness and safety of aqueous
      sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. EVIDENCE
      ACQUISITION: The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central
      Register of Controlled Trials were searched through December 22, 2012. English
      language randomized controlled trials were included if they compared sublingual
      immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy
      regimens and reported clinical outcomes. Studies of sublingual immunotherapy that
      are unavailable in the United States and for which a related immunotherapy is
      unavailable in the United States were excluded. Paired reviewers selected
      articles and extracted the data. The strength of the evidence for each comparison
      and outcome was graded based on the risk of bias (scored on allocation,
      concealment of intervention, incomplete data, sponsor company involvement, and
      other bias), consistency, magnitude of effect, and the directness of the
      evidence. RESULTS: Sixty-three studies with 5131 participants met the inclusion
      criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n = 1814
      patients) enrolled only children. The risk of bias was medium in 43 studies
      (68%). Strong evidence supports that sublingual immunotherapy improves asthma
      symptoms, with 8 of 13 studies reporting greater than 40% improvement vs the
      comparator. Moderate evidence supports that sublingual immunotherapy use
      decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies
      demonstrating greater than 40% improvement vs the comparator. Medication use for
      asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual
      immunotherapy with moderate grade evidence. Moderate evidence supports that
      sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined
      symptom and medication scores (20 studies), and disease-specific quality of life
      (8 studies). Local reactions were frequent, but anaphylaxis was not reported.
      CONCLUSIONS AND RELEVANCE: The overall evidence provides a moderate grade level
      of evidence to support the effectiveness of sublingual immunotherapy for the
      treatment of allergic rhinitis and asthma, but high-quality studies are still
      needed to answer questions regarding optimal dosing strategies. There were
      limitations in the standardization of adverse events reporting, but no life
      threatening adverse events were noted in this review.

PMID- 23532244
TI  - A 51-year-old man with HIV and cervicodorsal lipodystrophy (buffalo hump).

PMID- 23532245
TI  - Evaluation of the Trial to Assess Chelation Therapy (TACT): the scientific
      process, peer review, and editorial scrutiny.

PMID- 23532246
TI  - Concerns about reliability in the Trial to Assess Chelation Therapy (TACT).

PMID- 23532247
TI  - Macrolides and bronchiectasis: clinical benefit with a resistance price.

PMID- 23532240
TI  - Effect of disodium EDTA chelation regimen on cardiovascular events in patients
      with previous myocardial infarction: the TACT randomized trial.
AB  - IMPORTANCE: Chelation therapy with disodium EDTA has been used for more than 50
      years to treat atherosclerosis without proof of efficacy. OBJECTIVE: To determine
      if an EDTA-based chelation regimen reduces cardiovascular events. DESIGN,
      SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, 2 * 2 factorial
      randomized trial enrolling 1708 patients aged 50 years or older who had
      experienced a myocardial infarction (MI) at least 6 weeks prior and had serum
      creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and
      Canadian sites. Enrollment began in September 2003 and follow-up took place until
      October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total;
      n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during
      the trial. INTERVENTIONS: Patients were randomized to receive 40 infusions of a
      500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins,
      electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral
      vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly
      for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent
      discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the
      placebo group) because of adverse events. MAIN OUTCOME MEASURES: The prespecified
      primary end point was a composite of total mortality, recurrent MI, stroke,
      coronary revascularization, or hospitalization for angina. This report describes
      the intention-to-treat comparison of EDTA chelation vs placebo. To account for
      multiple interim analyses, the significance threshold required at the final
      analysis was P = .036. RESULTS: Qualifying previous MIs occurred a median of 4.6
      years before enrollment. Median age was 65 years, 18% were female, 9% were
      nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of
      the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82
      [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality
      (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70
      1.25]; P = .64), but the study was not powered for this comparison. The effect of
      EDTA chelation on the components of the primary end point other than death was of
      similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77
      [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI,
      0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81
      [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%;
      HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of
      patient dropout and treatment adherence did not alter the results. CONCLUSIONS
      AND RELEVANCE: Among stable patients with a history of MI, use of an intravenous
      chelation regimen with disodium EDTA, compared with placebo, modestly reduced the
      risk of adverse cardiovascular outcomes, many of which were revascularization
      procedures. These results provide evidence to guide further research but are not
      sufficient to support the routine use of chelation therapy for treatment of
      patients who have had an MI. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00044213.

PMID- 23532248
TI  - Is sublingual immunotherapy ready for use in the United States?

PMID- 23532249
TI  - JAMA patient page. Treatment of varicose veins.

PMID- 23532250
TI  - A structure-based design of new C2- and C13-substituted taxanes: tubulin binding
      affinities and extended quantitative structure-activity relationships using
      comparative binding energy (COMBINE) analysis.
AB  - Ten novel taxanes bearing modifications at the C2 and C13 positions of the
      baccatin core have been synthesized and their binding affinities for mammalian
      tubulin have been experimentally measured. The design strategy was guided by (i)
      calculation of interaction energy maps with carbon, nitrogen and oxygen probes
      within the taxane-binding site of beta-tubulin, and (ii) the prospective use of a
      structure-based QSAR (COMBINE) model derived from an earlier series comprising 47
      congeneric taxanes. The tubulin-binding affinity displayed by one of the new
      compounds (CTX63) proved to be higher than that of docetaxel, and an updated
      COMBINE model provided a good correlation between the experimental binding free
      energies and a set of weighted residue-based ligand-receptor interaction energies
      for 54 out of the 57 compounds studied. The remaining three outliers from the
      original training series have in common a large unfavourable entropic
      contribution to the binding free energy that we attribute to taxane
      preorganization in aqueous solution in a conformation different from that
      compatible with tubulin binding. Support for this proposal was obtained from
      solution NMR experiments and molecular dynamics simulations in explicit water.
      Our results shed additional light on the determinants of tubulin-binding affinity
      for this important class of antitumour agents and pave the way for further
      rational structural modifications.

PMID- 23532251
TI  - The complete mitochondrial genome of spittlebug Paphnutius ruficeps (Insecta:
      Hemiptera: Cercopidae) with a fairly short putative control region.
AB  - The mitochondrial genome of the spittlebug Paphnutius ruficeps is a double-strand
      DNA circular molecule of 14,841 bp with a total A and T content of 73.8%. It is
      one of the shortest genomes among published hemipteran mitogenomes and encodes 13
      protein-coding genes, 2 ribosome RNA genes and 22 transfer RNA (tRNA) genes. The
      gene order is consistent with the hypothesized ancestral arthropod genome
      arrangement. Most of the protein-coding genes use ATG as start and TAA as stop
      codon. The codons show an evident bias toward the nucleotides T and A at the
      third codon position and the most commonly used codons contain more A and T than
      their synonymous ones. The anticodons of the 22 tRNA genes are identical to those
      of the mitogenome of Philaenus spumarius, another studied spittlebug. All the
      tRNAs could be folded into traditional clover leaf secondary structures. The
      putative control region (traditionally called A + T-rich region) is the main non
      coding part of the mitogenome. The AT content of this region (74.5%) is not
      significantly higher than that of the total mitogenome (73.8%) and slightly lower
      than that of the N-chain protein-coding genes (75.3%). The absence of repeat
      sequences as well as its short length is the most obvious characteristics of the
      mitochondrial genome of Paphnutius ruficeps compared with those of other
      published hemipteran species.

PMID- 23532252
TI  - PTPalpha-mediated Src activation by EGF in human breast cancer cells.
AB  - Protein tyrosine phosphatase alpha (PTPalpha) functions as an activator of Src by
      dephosphorylating Tyr527/530, a critical negative regulatory site. The increase
      of PTPalpha catalytic activity requires its phosphorylation at Ser180 and/or
      Ser204 and its dissociation from PTPalpha/Grb2 complex. Here, we show that
      epidermal growth factor (EGF) stimulation increases the ability of PTPalpha to
      activate Src by dephosphorylating Tyr530 in BT-20 and SKBR3 breast cancer cell
      lines. Treatment of these cells with EGF transiently decreased the association of
      PTPalpha with Grb2 and enhanced PTPalpha catalytic activity via Ser180 and Ser204
      phosphorylation that was blocked by the protein kinase C delta (PKCdelta)
      inhibitor rottlerin or knockdown of PKCdelta by siRNA or by the overexpression of
      PTPalphaS180A/S204A mutant. PTPalpha siRNA blocked EGF-mediated Src activation in
      cancer cells and inhibited on colony formation, whereas control siRNA did not.
      These results suggested that PTPalpha links activation of epidermal growth factor
      receptor (EGFR) signaling with Src activation and may provide a novel therapeutic
      target for treatment of breast cancer.

PMID- 23532253
TI  - Cystic Adenomyoma simulates uterine malformation: A diagnostic dilemma: Case
      report of two unusual cases.
AB  - Cystic adenomyosis is a rare form of adenomyosis mostly seen in middle aged
      women.We report two cases of cystic adenomyosis in juvenile patients, which
      simulate uterine malformation and presented as a diagnostic dilemma. The first
      patient initially was diagnosed as uterus bicornis with a hematometra in
      obstructed rudimentary horn while the second patient was diagnosed as broad
      ligament fibroid. Surgical exploration by laparoscopic approach confirmed the
      diagnosis and excision of the cystic mass relieved the symptoms of the patients.

PMID- 23532254
TI  - S-adenosyl homocysteine hydrolase (SAHH) accelerates flagellar regeneration in
      Dunaliella salina.
AB  - S-adenosylhomocysteine hydrolase (SAHH) is an enzyme, which catalyzes the
      hydrolysis of S-adenosylhomocysteine (SAH) which is formed after the donation of
      the methyl group of S-adenosylmethionine (SAM) to a methyl acceptor in
      methylation reaction. As a potent regulator of methylation, SAHH plays a critical
      role in methylation reaction in the cells. Here we cloned the SAHH gene from
      unicellular green alga Dunaliella salina (dsSAHH) and investigated its effects on
      flagellar regeneration of D. salina, and found that dsSAHH was upregulated both
      at the protein and the transcription levels during pH shock-triggered flagellar
      regeneration of D. salina. The flagellar regeneration was accelerated when dsSAHH
      was overexpressed, but it was inhibited by SAHH inhibitor 3-deazaadenosine (DZA).
      Moreover, a receptor for activated C kinase 1 from D. salina (dsRACK1), which was
      identified to interact with dsSAHH, was increased when dsSAHH was overexpressed
      in D. salina as shown by real-time PCR. The findings of this study suggest that
      dsSAHH may participate in the regulation of flagellar regeneration of D. salina. 

PMID- 23532255
TI  - Do fibromyalgia patients use active pain management strategies? A cohort study.
AB  - OBJECTIVE: The aim of this study was to examine the types of pain management
      strategies used by patients with fibromyalgia. METHODS: A total of 158 patients
      with primary fibromyalgia attended a clinical visit to confirm the diagnosis.
      They completed 3 questionnaires: (i) a self-made questionnaire, (ii) Beck
      Depression Inventory IA (BDI IA), and (iii) Finnish version of Fibromyalgia
      Impact Questionnaire. The self-made questionnaire included questions about:
      intensity of current pain; general well-being; pain management strategies,
      including pain medications; efficacy of the pain management methods; current
      health problems other than fibromyalgia. The pain management strategies were
      subcategorized (e.g., physical exercise, massage and heat treatment). The
      strategies were also divided into active and passive types. RESULTS: The most
      frequently reported pain management strategies were physical exercise (54%),
      physical therapy (32%) and cold treatment (27%). The use of active pain
      management strategies, BDI IA < 10 points and age were independent predictors of
      the reported pain management efficacy. Patients who used active pain management
      strategies reported better efficacy with the BDI IA score >= 10 points.
      CONCLUSION: Active pain management strategies are most efficacious for
      fibromyalgia patients, regardless of the severity of fibromyalgia or optional
      comorbid depression.

PMID- 23532256
TI  - [First Brazilian Guidelines for Familial Hypercholesterolemia].

PMID- 23532258
TI  - Effects of immunosuppression on alpha and beta cell renewal in transplanted mouse
      islets.
AB  - AIMS/HYPOTHESIS: Immunosuppressive drugs used in human islet transplantation
      interfere with the balance between beta cell renewal and death, and thus may
      contribute to progressive graft dysfunction. We analysed the influence of
      immunosuppressants on the proliferation of transplanted alpha and beta cells
      after syngeneic islet transplantation in streptozotocin-induced diabetic mice.
      METHODS: C57BL/6 diabetic mice were transplanted with syngeneic islets in the
      liver and simultaneously abdominally implanted with a mini-osmotic pump
      delivering BrdU alone or together with an immunosuppressant (tacrolimus,
      sirolimus, everolimus or mycophenolate mofetil [MMF]). Glycaemic control was
      assessed for 4 weeks. The area and proliferation of transplanted alpha and beta
      cells were subsequently quantified. RESULTS: After 4 weeks, glycaemia was
      significantly higher in treated mice than in controls. Insulinaemia was
      significantly lower in mice treated with everolimus, tacrolimus and sirolimus.
      MMF was the only immunosuppressant that did not significantly reduce beta cell
      area or proliferation, albeit its levels were in a lower range than those used in
      clinical settings. CONCLUSIONS/INTERPRETATION: After transplantation in diabetic
      mice, syngeneic beta cells have a strong capacity for self-renewal. In contrast
      to other immunosuppressants, MMF neither impaired beta cell proliferation nor
      adversely affected the fractional beta cell area. Although human beta cells are
      less prone to proliferate compared with rodent beta cells, the use of MMF may
      improve the long-term outcome of islet transplantation.

PMID- 23532257
TI  - Genome-wide association study in a Chinese population identifies a susceptibility
      locus for type 2 diabetes at 7q32 near PAX4.
AB  - AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been
      discovered in European populations. We performed genome-wide association studies
      (GWAS) in a Chinese population with the aim of identifying novel variants for
      type 2 diabetes in Asians. METHODS: We performed a meta-analysis of three GWAS
      comprising 684 patients with type 2 diabetes and 955 controls of Southern Han
      Chinese descent. We followed up the top signals in two independent Southern Han
      Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in
      silico replication in multiple populations. RESULTS: We identified CDKN2A/B and
      four novel type 2 diabetes association signals with p < 1 * 10(-5) from the meta
      analysis. Thirteen variants within these four loci were followed up in two
      independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated
      with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p
      meta = 2.6 * 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication
      revealed consistent associations across multiethnic groups, including five East
      Asian populations (p meta = 2.3 * 10(-10)) and a population of European descent
      (p = 8.6 * 10(-3)). The rs10229583 risk variant was associated with elevated
      fasting plasma glucose, impaired beta cell function in controls, and an earlier
      age at diagnosis for the cases. The novel variant lies within an islet-selective
      cluster of open regulatory elements. There was significant heterogeneity of
      effect between Han Chinese and individuals of European descent, Malaysians and
      Indians. CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as
      a novel locus for type 2 diabetes in Chinese and other populations and provides
      new insights into the pathogenesis of type 2 diabetes.

PMID- 23532259
TI  - Relationship between vascular reactivity and expression of HMGB1 in a rat model
      of septic aorta.
AB  - INTRUODUCTION: High mobility group box 1 (HMGB1), a ubiquitous nuclear protein,
      induces several inflammatory diseases and functions as a fatal factor when
      released extracellularly. The effect of HMGB1 on vascular reactivity during
      sepsis remains to be clarified. METHODS: A rat model of abdominal sepsis was
      produced by cecal ligation and puncture (CLP) under sevoflurane anesthesia (n =
      28). Anti-HMGB1 antibody at a dose of 4 or 0.4 mg/kg, or normal saline was
      injected twice intravenously, i.e., immediately after the CLP surgery and 4 h
      thereafter. Rats in the sham group underwent laparotomy, and the cecum was
      manipulated but not ligated or punctured. The descending thoracic aorta was
      excised 12 h after the CLP surgery and cut into rings of approximately 3 mm in
      length. Changes in the expression of HMGB1 and vascular reactivity were examined
      in the rings shortly after harvest and 4 h thereafter. RESULTS: HMGB1 was
      identified immunohistochemically and by Western blotting in the nuclei of
      vascular endothelial and smooth muscle cells in all groups shortly after excision
      of the aorta, but its expression was augmented only in the CLP groups 4 h
      thereafter. Degenerated smooth muscle cells were also observed after CLP. Anti
      HMGB1 antibody dose-dependently inhibited the augmentation of HMGB1 expression
      and the morphological changes induced by CLP. The expression of HMGB1 partly
      correlated with suppression of vascular reactivity. CONCLUSION: The present
      results strongly suggest that HMGB1 plays an important role in vascular
      malfunction from an early phase of sepsis.

PMID- 23532260
TI  - Single-mode biological distributed feedback laser.
AB  - Single-mode second order distributed feedback (DFB) lasers of riboflavin (vitamin
      B2) doped gelatine films on nanostructured low refractive index material are
      demonstrated. Manufacturing is based on a simple UV nanoimprint and spin-coating.
      Emission wavelengths of 543 nm and 562 nm for two different grating periods are
      reported.

PMID- 23532261
TI  - The consequences of gene flow for local adaptation and differentiation: a two
      locus two-deme model.
AB  - We consider a population subdivided into two demes connected by migration in
      which selection acts in opposite direction. We explore the effects of
      recombination and migration on the maintenance of multilocus polymorphism, on
      local adaptation, and on differentiation by employing a deterministic model with
      genic selection on two linked diallelic loci (i.e., no dominance or epistasis).
      For the following cases, we characterize explicitly the possible equilibrium
      configurations: weak, strong, highly asymmetric, and super-symmetric migration,
      no or weak recombination, and independent or strongly recombining loci. For
      independent loci (linkage equilibrium) and for completely linked loci, we derive
      the possible bifurcation patterns as functions of the total migration rate,
      assuming all other parameters are fixed but arbitrary. For these and other cases,
      we determine analytically the maximum migration rate below which a stable fully
      polymorphic equilibrium exists. In this case, differentiation and local
      adaptation are maintained. Their degree is quantified by a new multilocus version
      of [Formula: see text] and by the migration load, respectively. In addition, we
      investigate the invasion conditions of locally beneficial mutants and show that
      linkage to a locus that is already in migration-selection balance facilitates
      invasion. Hence, loci of much smaller effect can invade than predicted by one
      locus theory if linkage is sufficiently tight. We study how this minimum amount
      of linkage admitting invasion depends on the migration pattern. This suggests the
      emergence of clusters of locally beneficial mutations, which may form 'genomic
      islands of divergence'. Finally, the influence of linkage and two-way migration
      on the effective migration rate at a linked neutral locus is explored. Numerical
      work complements our analytical results. 

PMID- 23532262
TI  - Being in an exchange process: experiences of patient participation in multimodal
      pain rehabilitation.
AB  - OBJECTIVE: To explore primary healthcare patients' experiences of patients
      participation in multimodal pain rehabilitation. PATIENTS AND METHODS: A total of
      17 patients who had completed multimodal rehabilitation for persistent pain were
      interviewed. The interviews were analysed using qualitative content analysis.
      RESULTS: One theme, Being in an exchange process, and 4 categories emerged. The
      theme depicted patient participation as a continuous exchange of emotions,
      thoughts and knowledge. The category Fruitful encounters represented the basic
      prerequisites for patient participation through dialogue and platforms to meet.
      Patients' emotional and cognitive resources and restrictions, as well as
      knowledge gaps, were conditions influencing patient participation in the category
      Inequality in co-operation. Mutual trust and respect were crucial conditions in
      patient's personal relationships with the health professionals, forming the
      category Confidence-inspiring alliance. In the category Competent health
      professionals, the health professionals' expertise, empathy and personal
      qualities, were emphasized to favour patient participation. CONCLUSION: Patient
      participation can be understood as complex and individualized. A confidence
      inspiring alliance enables a trusting relationship to be formed between patients
      and health professionals. Patients emphasized that health professionals need to
      play an active role in building common ground in the interaction. Understanding
      each patient's needs in the participation process may favour patient
      participation.

PMID- 23532263
TI  - Usefulness of cross-table lateral view radiograph for the diagnosis of cam-type
      femoroacetabular impingement.
AB  - The purpose of this study was to examine the usefulness of cross-table view in
      the clinical diagnosis of cam-type femoroacetabular impingement (FAI). We
      measured the alpha angles on radiographs taken in cross-table lateral view in 39
      hips with cam-type FAI and compared with those measured in 45 control hips. Alpha
      angles ranged from 30 degrees  to 78 degrees  (mean 56 degrees ) in the control
      group and from 47 degrees  to 120 degrees  (mean 81.1 degrees ) in the FAI group.
      From a canonial discriminant analysis, the cutoff value of alpha angle was 68.2
      degrees . Sensitivity analysis showed a sensitivity of 87.18 %, specificity of
      88.89 %, and accuracy of 88.3 %. Cross-table lateral view is useful for the
      diagnosis of cam-type FAI. 

PMID- 23532265
TI  - Experimental model of intervertebral disc degeneration by needle puncture in
      Wistar rats.
AB  - Animal models of intervertebral disc degeneration play an important role in
      clarifying the physiopathological mechanisms and testing novel therapeutic
      strategies. The objective of the present study is to describe a simple animal
      model of disc degeneration involving Wistar rats to be used for research studies.
      Disc degeneration was confirmed and classified by radiography, magnetic resonance
      and histological evaluation. Adult male Wistar rats were anesthetized and
      submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and
      8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by
      fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the
      contralateral annulus fibrosus, rotated 360 degrees  twice, and held for 30 s. To
      grade the severity of intervertebral disc degeneration, we measured the
      intervertebral disc height from radiographic images 7 and 30 days after the
      injury, and the signal intensity T2-weighted magnetic resonance imaging.
      Histological analysis was performed with hematoxylin-eosin and collagen fiber
      orientation using picrosirius red staining and polarized light microscopy.
      Imaging and histological score analyses revealed significant disc degeneration
      both 7 and 30 days after the lesion, without deaths or systemic complications.
      Interobserver histological evaluation showed significant agreement. There was a
      significant positive correlation between histological score and intervertebral
      disc height 7 and 30 days after the lesion. We conclude that the tail disc
      puncture method using Wistar rats is a simple, cost-effective and reproducible
      model for inducing disc degeneration.

PMID- 23532264
TI  - Impact of HPV infection on the development of head and neck cancer.
AB  - Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC)
      is considered to be a distinct clinical entity with better prognosis than the
      classical tobacco- and alcohol-associated tumors. The increasing incidence of
      this neoplasia during the last decades highlights the need to better understand
      the role of HPV in the development of these cancers. Although the proportion of
      HNSCC attributed to HPV varies considerably according to anatomical site, overall
      approximately 25% of all HNSCC are HPV-DNA positive, and HPV-16 is by far the
      most prevalent type. In this review we discuss the existing evidence for a causal
      association between HPV infection and HNSCC at diverse anatomical head and neck
      subsites.

PMID- 23532266
TI  - Association of MDR1 gene polymorphisms with the risk of hepatocellular carcinoma
      in the Chinese Han population.
AB  - The multidrug resistance 1 gene (MDR1) is an important candidate gene for
      influencing susceptibility to hepatocellular carcinoma (HCC). The objective of
      the present study was to evaluate the association of MDR1 polymorphisms with the
      risk of HCC in the Chinese Han population. A total of 353 HCC patients and 335
      healthy subjects were enrolled in the study. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR
      (CRS-PCR) and DNA sequencing methods were used to identify MDR1 gene
      polymorphisms. Two allelic variants (c.335T>C and c.3073A>C) were detected. The
      CC genotype of the c.335T>C polymorphism was associated with an increased risk of
      developing HCC compared to the TT genotype (OR = 2.161, 95%CI = 1.350-3.459, chi2
      = 10.55, P = 0.0011). The risk of HCC was significantly higher for the CC
      genotype in the c.3073A>C polymorphism compared to the AA genotype in the studied
      populations (CC vs AA: OR = 2.575, 95%CI = 1.646-4.028, chi2 = 17.64, P <
      0.0001). The C allele of the c.335T>C and c.3073A>C variants may contribute to
      the risk of HCC (C vs T of c.335T>C: OR = 1.512, 95%CI = 1.208-1.893, chi2 =
      13.07, P = 0.0003, and C vs A of c.3073A>C: OR = 1.646, 95%CI = 1.322-2.049, chi2
      = 20.03, P < 0.0001). The c.335T>C and c.3073A>C polymorphisms of the MDR1 gene
      were associated with the risk of occurrence of HCC in the Chinese Han population.
      Further investigations are needed to confirm these results in larger different
      populations.

PMID- 23532267
TI  - Gastric emptying of water in children with severe functional fecal retention.
AB  - The objective of this study was to evaluate gastric emptying (GE) in pediatric
      patients with functional constipation. GE delay has been reported in adults with
      functional constipation. Gastric emptying studies were performed in 22 children
      with chronic constipation, fecal retention and fecal incontinence, while
      presenting fecal retention and after resuming regular bowel movements. Patients
      (18 boys, median age: 10 years; range: 7.2 to 12.7 years) were evaluated in a
      tertiary pediatric gastroenterology clinic. Gastric half-emptying time of water
      (reference range: 12 +/- 3 min) was measured using a radionuclide technique
      immediately after first patient evaluation, when they presented fecal impaction
      (GE1), and when they achieved regular bowel movements (GE2), 12 +/- 5 weeks after
      GE1. At study admission, 21 patients had reported dyspeptic symptoms, which were
      completely relieved after resuming regular bowel movements. Medians (and
      interquartile ranges) for GE1 and GE2 were not significantly different [27.0 (16)
      and 27.5 (21) min, respectively (P = 0.10)]. Delayed GE seems to be a common
      feature among children with chronic constipation and fecal retention. Resuming
      satisfactory bowel function and improvement in dyspeptic symptoms did not result
      in normalization of GE data.

PMID- 23532268
TI  - Maternal protein restriction affects gene expression and enzyme activity of
      intestinal disaccharidases in adult rat offspring.
AB  - This study investigated the consequences of intrauterine protein restriction on
      the gastrointestinal tract and particularly on the gene expression and activity
      of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed
      isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein
      (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group)
      were evaluated at 3 or 16 weeks of age. Maternal protein restriction during
      pregnancy produced offspring with growth restriction from birth (5.7 +/- 0.1 vs
      6.3 +/- 0.1 g; mean +/- SE) to weaning (42.4 +/- 1.3 vs 49.1 +/- 1.6 g), although
      at 16 weeks of age their body weight was similar to control (421.7 +/- 8.9 and
      428.5 +/- 8.5 g). Maternal protein restriction also increased lactase activity in
      the proximal (0.23 +/- 0.02 vs 0.15 +/- 0.02), medial (0.30 +/- 0.06 vs 0.14 +/-
      0.01) and distal (0.43 +/- 0.07 vs 0.07 +/- 0.02 U.g-1.min-1) small intestine,
      and mRNA lactase abundance in the proximal intestine (7.96 +/- 1.11 vs 2.38 +/-
      0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein
      restriction increased sucrase activity (1.20 +/- 0.02 vs 0.91 +/- 0.02 U.g-1.min
      1) and sucrase mRNA abundance (4.48 +/- 0.51 vs 1.95 +/- 0.17 relative units) in
      the duodenum of 16-week-old rats. In conclusion, the present study shows for the
      first time that intrauterine protein restriction affects gene expression of
      intestinal enzymes in offspring.

PMID- 23532269
TI  - Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced
      acute lung injury by inhibition of CD14 and TLR4 expression.
AB  - We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1,
      intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its
      effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4
      expression in lung tissue of anesthetized, ventilated rats. Twenty-four male
      Wistar rats were randomly divided into three groups of 8 rats each: control, LPS,
      and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology,
      and tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)
      levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time
      polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14
      and TLR4 protein expression was determined by Western blot. The pathological
      scores were 1.2 +/- 0.9, 3.3 +/- 1.1, and 1.9 +/- 1.0 for the control, LPS, and
      LPS+Prop groups, respectively, with statistically significant differences between
      control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05).
      The administration of LPS resulted in a significant increase in TNF-alpha and IL
      1beta levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with
      propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and
      TLR4 mRNA levels were increased in the LPS group (1.48 +/- 0.05 and 1.26 +/-
      0.03, respectively) compared to the control group (1.00 +/- 0.20 and 1.00 +/-
      0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16
      +/- 0.05 and 1.12 +/- 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein
      levels were elevated in the LPS group compared to the control group (P < 0.05),
      while propofol treatment partially decreased the expression of CD14 and TLR4
      protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents
      lung injury, most likely by inhibition of CD14 and TLR4 expression.

PMID- 23532270
TI  - An improved experimental model for peripheral neuropathy in rats.
AB  - A modification of the Bennett and Xie chronic constriction injury model of
      peripheral painful neuropathy was developed in rats. Under tribromoethanol
      anesthesia, a single ligature with 100% cotton glace thread was placed around the
      right sciatic nerve proximal to its trifurcation. The change in the hind paw
      reflex threshold after mechanical stimulation observed with this modified model
      was compared to the change in threshold observed in rats subjected to the Bennett
      and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was
      measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days
      after surgery, and this threshold was compared to that measured in sham rats. All
      injury models produced significant hyperalgesia in the operated hind limb. The
      modified model produced mean +/- SD thresholds in g (19.98 +/- 3.08, 14.98 +/-
      1.86, and 13.80 +/- 1.00 at 2, 7, and 14 days after surgery, respectively)
      similar to those obtained with the spinal ligation model (20.03 +/- 1.99, 13.46
      +/- 2.55, and 12.46 +/- 2.38 at 2, 7, and 14 days after surgery, respectively),
      but less variable when compared to the Bennett and Xie model (21.20 +/- 8.06,
      18.61 +/- 7.69, and 18.76 +/- 6.46 at 2, 7, and 14 days after surgery,
      respectively). The modified method required less surgical skill than the spinal
      nerve ligation model.

PMID- 23532271
TI  - Effect and the probable mechanisms of silibinin in regulating insulin resistance
      in the liver of rats with non-alcoholic fatty liver.
AB  - Our previous study has shown that reduced insulin resistance (IR) was one of the
      possible mechanisms for the therapeutic effect of silibinin on non-alcoholic
      fatty liver disease (NAFLD) in rats. In the present study, we investigated the
      pathways of silibinin in regulating hepatic glucose production and IR
      amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided
      into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD +
      silibinin group (high-fat diet + 0.5 mg kg-1.day-1 silibinin, starting at the
      beginning of the protocol). Both subcutaneous and visceral fat was measured.
      Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose
      tolerance test and insulin tolerance test (ITT) were performed. The expression of
      adipose triglyceride lipase (ATGL) and of genes associated with hepatic
      gluconeogenesis was evaluated. Silibinin intervention significantly protected
      liver function, down-regulated serum fat, and improved IR, as shown by decreased
      HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by
      reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and
      inhibited gluconeogenesis by down-regulating associated genes such as Forkhead
      box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin
      was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity,
      enhancement of lipolysis and inhibition of gluconeogenesis might be the
      underlying mechanisms.

PMID- 23532273
TI  - The third decade of microfluidics.

PMID- 23532272
TI  - River barriers and cryptic biodiversity in an evolutionary museum.
AB  - The Riverine Barriers Hypothesis (RBH) posits that tropical rivers can be
      effective barriers to gene flow, based on observations that range boundaries
      often coincide with river barriers. Over the last 160 years, the RBH has received
      attention from various perspectives, with a particular focus on vertebrates in
      the Amazon Basin. To our knowledge, no molecular assessment of the RBH has been
      conducted on birds in the Afrotropics, despite its rich avifauna and many
      Afrotropical bird species being widely distributed across numerous watersheds and
      basins. Here, we provide the first genetic evidence that an Afrotropical river
      has served as a barrier for birds and for their lice, based on four understory
      bird species collected from sites north and south of the Congo River. Our results
      indicate near-contemporaneous, Pleistocene lineage diversification across the
      Congo River in these species. Our results further indicate differing levels of
      genetic variation in bird lice; the extent of this variation appears linked to
      the life-history of both the host and the louse. Extensive cryptic diversity
      likely is being harbored in Afrotropical forests, in both understory birds and
      their lice. Therefore, these forests may not be "museums" of old lineages.
      Rather, substantial evolutionary diversification may have occurred in
      Afrotropical forests throughout the Pleistocene, supporting the Pleistocene
      Forest Refuge Hypothesis. Strong genetic variation in birds and their lice within
      a small part of the Congo Basin forest indicates that we may have grossly
      underestimated diversity in the Afrotropics, making these forests home of
      substantial biodiversity in need of conservation.

PMID- 23532274
TI  - Visible light initiated and collapsed resistive switching in TbMnO3/Nb:SrTiO3
      heterojunctions.
AB  - Simple oxide heterostructures have been fabricated by depositing TbMnO3 thin
      films on Nb:SrTiO3 substrates at different temperatures. Remarkable switching
      with an on/off resistance ratio of ~5000 is found in the sample grown at 720 
      degrees C, while only tiny resistive hysteresis can be observed in the sample
      grown at 650  degrees C. A jump switching in the I-V loop at the lower resistance
      state with negative bias is initiated by a visible light pulse in the sample
      grown at 650  degrees C, whereas a drop switching can be observed in the sample
      grown at 720  degrees C. A trapping-detrapping process along the TbMnO3/Nb:SrTiO3
      interfaces is proposed to explain the anomalous photoresponse.

PMID- 23532276
TI  - Biochemical changes of fresh water cyanobacteria Dolichospermum flos-aquae NTMS07
      to chromium-induced stress with special reference to antioxidant enzymes and
      cellular fatty acids.
AB  - This investigation examined the efficiency of Dolichospermum flos-aquae NTMS07 in
      the removal of Cr(VI) from exposure water at various concentrations (2.5, 5, 7.5,
      10 mg/L) over different time intervals of contact (1-5 days). Chromium removal
      was maximum at 2.5 mg/L, and decreased with increased concentration. The
      responses of the antioxidative enzymes superoxide dismutase (SOD) and catalase
      (CAT) were measured, and the composition of fatty acids was evaluated at a
      concentration of 5 mg Cr/L. Significant increases in the activity levels of SOD
      and CAT were obtained. The level of total unsaturated fatty acids decreased with
      exposure to Cr. It is proposed that the observed decrease in total unsaturated
      fatty acid level is a defense mechanism against Cr-induced oxidative stress and
      cell membrane damage.

PMID- 23532275
TI  - A psychometric evaluation of the Arm Motor Ability Test.
AB  - OBJECTIVE: To further examine the psychometric properties of a 9-item version of
      the Arm Motor Ability Test (AMAT-9) in persons with stroke. SUBJECTS: Thirty-two
      community-dwelling persons > 6 months post-stroke undergoing robotics treatment
      (mean age = 56.0 years, time post-stroke = 4.1 years, National Institutes of
      Health Stroke Scale score = 4.1, and AMAT-9 score = 1.22). METHODS: Construct
      validity (including Rasch analyses) used baseline data prior to treatment (n =
      32). Standardized response mean was calculated for subjects completing the
      protocol (n = 29). The Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment
      (FMA), Action Research Arm Test (ARAT), and Stroke Impact Scale (SIS) were also
      administered. RESULTS: Spearman-rank correlation coefficients between AMAT-9 and
      the WMFT, FMA, and ARAT were strong (0.78-0.79, all p < 0.001). The correlation
      between the AMAT-9 and SIS Hand Function sub-score was stronger than that between
      the AMAT-9 and the Communication sub-score (0.40, p = 0.025 and -0.16, p = 0.39,
      respectively). Rasch analyses provided evidence for an appropriate hierarchical
      structure of item difficulties, unidimensionality, and good reliability. The AMAT
      demonstrated a comparable standardized response mean of 0.98. CONCLUSIONS: The
      AMAT-9 is valid and responsive among subjects scoring in the lower range of the
      scale. It has the advantage of assessing function and by eliminating the standing
      item from the previous iteration, it may be more easily used with severely
      impaired patients.

PMID- 23532277
TI  - The relationship between heavy metal (Cd, Co, Cu, Ni and Pb) levels and the size
      of benthic, benthopelagic and pelagic fish species, Persian Gulf.
AB  - The concentration of heavy metals was determined in tissues of sole (Euryglossa
      orientalis), mullet (Liza abu) and croacker fish (Johnius belangerii) from Musa
      estuary. Generally, the highest concentration of the studied metals in the three
      species was found in the liver tissue. The levels of Cd and Cu in fish liver were
      J. belangerii = E. orientalis > L. abu and E. orientalis > L. abu > J. belangerii
      respectively. The concentrations of Cd and Cu in fish gills were E. orientalis >
      L. abu = J. belangerii and E. orientalis > L. abu > J. belangerii, respectively,
      and the level of Cu in muscle was E. orientalis > L. abu = J. belangerii. The
      results of linear regression analysis indicated that highly significant (p <
      0.001) negative relationships were found between fish size and Cd concentrations
      in the liver of L. abu and Pb in the gills of J. belangerii.

PMID- 23532278
TI  - [Peer review: demand-side crisis or change of values?].

PMID- 23532279
TI  - Contemporary quality improvement.

PMID- 23532280
TI  - [Silhouette scales and body satisfaction in adolescents: a systematic literature
      review].
AB  - The purpose of this study was to summarize studies on adolescents' body
      satisfaction, focusing on the use of silhouette scales. A systematic review was
      carried out on MEDLINE, LILACS, SciELO, and in unpublished papers. The final
      analysis included 36 studies. The majority adopted the scale proposed by Stunkard
      et al., self-administered, presented in ascending order and on a single sheet of
      paper. Most studies compared characteristics on satisfaction and dissatisfaction,
      used the chi-square test, and did not test for confounding. Among 18 studies
      included in the meta-analysis, prevalence of body dissatisfaction ranged from
      32.2% to 83%. The review showed wide heterogeneity between studies (p-value =
      0.000; I(2) = 87.39) even after sub-group analysis and the absence of relevant
      information for proper comparison of studies. The article concludes by
      recommending greater rigor in application of the scales and presentation of study
      methods on body satisfaction assessed by silhouette scales, in addition to new
      methodological studies and those that elucidate factors related to body
      satisfaction.

PMID- 23532281
TI  - [Systematic review of epidemiological studies on interpersonal discrimination and
      mental health].
AB  - The article describes epidemiological studies on the relationship between
      interpersonal discrimination and mental health outcomes, updating previous
      literature reviews on the topic. The review included 34 papers published in
      PubMed from 2000 to 2010, 68% of which were based on convenience samples and 82%
      with a cross-sectional design. Positive and statistically significant
      associations were observed between discrimination and adverse mental health
      outcomes, particularly substance use, depression, and alcohol-related disorders.
      Only one third of the studies explicitly adopted a specific theoretical framework
      to interpret the examined relationships. Mirroring previous reviews,
      discrimination was positively and consistently associated with adverse mental
      health outcomes. However, future studies should employ robust designs for causal
      inference, use discrimination instruments with good psychometric properties, and
      adopt theoretical frameworks to interpret their findings.

PMID- 23532282
TI  - Epidemiologists working together with anthropologists: lessons from a study to
      evaluate the epidemiological impact of a city-wide sanitation program.
AB  - This paper discusses the role of qualitative approaches in epidemiological
      studies, beginning with a general discussion of epidemiological and
      anthropological methods. It focuses on a case study of the health impact of an
      environmental intervention carried out in Salvador, Bahia State, Brazil. Most of
      the precedent studies fields, based on primary date, use to devote little
      attention to the methodological and theorethical questions attached to long-term
      studies. Four specific aspects of this experience are highlighted: (a) drawing up
      epidemiological study; (b) construction of an observational instrument to measure
      hygiene habits; (c) an ethnographic study that was carried out before the
      epidemiological study; (d) observation of the effects of health intervention on
      health inequalities. Finally, the report details how the findings of qualitative
      and quantitative studies might be synthesized. It provides a critical overview of
      follow-up strategies, illustrated with proper examples whenever possible.

PMID- 23532283
TI  - [Analysis of coverage in the Mortality Information System in Olinda, Pernambuco
      State, Brazil].
AB  - This article analyzes the coverage of the Mortality Information System (SIM) in
      Olinda, Pernambuco State, Brazil, in the year 2008. The study involved secondary
      data from SIM on deaths (excluding stillbirths) in residents of the municipality
      and primary data from the Active Search of Deaths and Births in the Northeast and
      Legal Amazonia, which collected the events from multiple sources and located
      deaths that had not been reported to the system. Coverage was calculated as the
      number of deaths recorded in SIM divided by the total (SIM + active search). The
      study showed 94.8% coverage and detected an important contribution by notary
      public offices to the identification of deaths that were missing from the SIM. Of
      these unreported deaths, 29.7% occurred in health services, 49% occurred at home
      with death certificates signed by private physicians, and 25.5% had been attested
      by the forensic examiner's office. The method allowed calculating the coverage
      rate for the Mortality Information System in a municipality in the metropolitan
      area. Despite the low proportion of deaths missing in the system, the study
      detected problems with data collection and flow.

PMID- 23532284
TI  - Understanding the relationship between socioeconomic status, smoking cessation
      services provided by the health system and smoking cessation behavior in Brazil.
AB  - Increasing the effectiveness of smoking cessation policies requires greater
      consideration of the cultural and socioeconomic complexities of smoking. The
      purpose of this paper is to explore the association between socioeconomic status
      and "selected midpoints" linked to smoking cessation in Brazil. Data was
      collected from a representative sample of urban adult smokers as part of the ITC
      Brazil Survey (2009, N = 1,215). After controlling for age and gender, there were
      no statistically significant differences quit attempts in the last six months
      between individuals with different socioeconomic status. However, smokers with
      high socioeconomic status visited a doctor 1.54 times more often than those with
      low socioeconomic status (p-value = 0.017), and were also 1.65 times more likely
      to receive advice to quit smoking (p-value = 0.025). Our results demonstrate that
      disparities in health and socioeconomic status are still a major challenge for
      policymakers to increase the population impact of tobacco control actions
      worldwide.

PMID- 23532285
TI  - [A case-control study of factors associated with repeat teen pregnancy based on a
      sample from a university maternity hospital].
AB  - Repeat teen pregnancy is a frequent issue and is considered an aggravating factor
      for increased maternal and fetal morbidity and social problems. The aim of the
      study was to identify factors associated with repeat teen pregnancy. A case
      control study was conducted in 90 postpartum adolescents with more than one
      pregnancy (cases) and 90 adult women with a history of only one pregnancy during
      adolescence (controls). Statistical analysis used hierarchical logistic
      regression with 5% significance. Early sexual initiation (< 15 years), early age
      at first pregnancy (< 16 years), not raising the children themselves, and low
      family income (< one minimum wage) were associated with repeat teenage pregnancy,
      while partner change was inversely associated. Repeat teen pregnancy was mainly
      associated with reproductive and socioeconomic factors. Partner change appeared
      as a protective factor. Measures should be adopted during the postpartum period
      of teenage mothers in order to avoid repeat pregnancy.

PMID- 23532286
TI  - [Prevalence and factors associated with high blood pressure, awareness, and
      treatment among elderly in Southern Brazil].
AB  - The aim of this study was to describe prevalence, awareness, and treatment of
      high blood pressure (HBP) and associated factors among the elderly in
      Florianopolis, Santa Catarina State, Brazil. This cross-sectional population
      based study used a complex sampling design. HBP was defined as elevated blood
      pressure (by direct measurement), use of antihypertensive medication, or prior
      diagnosis. The association of outcomes with independent variables was assessed by
      Poisson regression. One-thousand seven hundred and five participants were
      interviewed. Of these, 84.6% presented HBP, 77.5% were aware of their condition,
      and 79.1% were on antihypertensive medication. Prevalence of HBP was associated
      with age, functional capacity, and body mass index (BMI). Awareness of the
      condition was associated with age, gender, BMI, self-rated health, and recent
      medical consultation. Treatment was associated with gender, functional capacity,
      self-rated health, and recent medical consultation. Although public health
      policies should include everyone, unequal distribution of HBP in the population
      should be addressed through targeted preventive, diagnostic, and therapeutic
      measures.

PMID- 23532287
TI  - [Vaccination coverage and factors associated with incomplete basic vaccination
      schedule in 12-month-old children, Sao Luis, Maranhao State, Brazil, 2006].
AB  - The study aimed to evaluate vaccination coverage and factors associated with
      incomplete basic vaccination schedule at 12 months of age in 427 children aged 12
      59 months in Sao Luis, Maranhao State, Brazil, 2006. This cross-sectional,
      population-based household survey used complex cluster sampling. Poisson
      regression with robust adjustment of variance was applied. Complete basic
      vaccination coverage was 71.9% for applied doses, 61.8% for valid doses, and
      23.6% for correct doses. Hepatitis B and tetravalent vaccines showed higher
      percentages of doses on dates or at intervals lower than recommended. Percentages
      of delayed vaccination were high, except for BCG. Incomplete basic vaccination
      was more frequent in girls and children from low-income and black families.
      Racial, gender, and socioeconomic factors posed barriers to complete vaccination,
      thus emphasizing the need for policies to address such inequalities.

PMID- 23532288
TI  - [Association between insomnia symptoms, daytime napping, and falls in community
      dwelling elderly].
AB  - This study focused on associations between insomnia symptoms, daytime napping,
      and falls in community-dwelling elderly, using a population-based cross-sectional
      design and probability sample with 689 community-dwelling elders. The protocol
      consisted of self-reported and physical performance variables. The study used
      univariate and multivariate logistic regression analysis with statistical
      significance set at p < 0.05. Prevalence rates for insomnia symptoms and daytime
      napping were 49.9% (n = 339) and 62.8% (n = 432), respectively. 14.4% reported a
      single fall and 11.9% reported multiple falls. Falls were associated with female
      gender (OR = 7.73; 95%CI: 3.03-19.72), age > 80 (OR = 3.48; 95%CI: 1.54-7.85),
      napping (OR = 2.24; 95%CI: 1.24-4.05), and depressive symptoms (OR = 1.98; 95%CI:
      1.11-3.53). The association between daytime napping and falls corroborates data
      from international research. Identifying modifiable risk factors may help
      programs to prevent falls in the elderly.

PMID- 23532289
TI  - [Validity and reliability of data and avoidability of the underlying cause of
      neonatal deaths in the intensive care unit of the North-Northeast Perinatal Care
      Network].
AB  - The aim of this study was to analyze the validity and reliability of data and the
      avoidability of neonatal deaths in the intensive care unit in the North-Northeast
      Perinatal Care Network (RENOSPE). The sample included 53 neonatal deaths recorded
      in the RENOSPE database that occurred in a maternity hospital in Teresina, Piaui
      State, Brazil. Validity was assessed by comparing causes recorded in the database
      with those from patient charts and calculating kappa index, sensitivity, and
      positive predictive value (PPV). Analysis of avoidability used the Brazilian List
      of Avoidable Deaths. When causes of death recorded in the RENOSPE database were
      compared with patient charts, kappa was 47.6% for maternal causes and 73.9% for
      congenital malformations, sensitivity was 95% and 83.3%, and PPV was 88.9% and
      85.7%, respectively. The percentage of avoidable deaths in the RENOSPE database
      was high, attributable to lack of adequate prenatal care in 72% of cases. In
      conclusion, causes classified as congenital malformations were valid, and the
      high rate of avoidable deaths points to the need for improved prenatal care.

PMID- 23532290
TI  - [Methodological description of accelerometry for measuring physical activity in
      the 1993 and 2004 Pelotas (Brazil) birth cohorts].
AB  - The aim of this study was to characterize the methodology of data collection on
      physical activity using accelerometry in two birth cohorts (2004 and 1993) in
      Pelotas, Rio Grande do Sul State, Brazil, at the 6-7 and 18-year follow-up
      visits, respectively. During visits to the study headquarters for a health
      evaluation, cohort subjects received the accelerometer to be worn on the wrist
      for 5 to 8 days, after which the device was retrieved at their homes. Genea and
      GENEActiv triaxial estimators of gravity (g) acceleration were employed.
      Accelerometry data were collected from 3,331 children (93.7% of those included in
      follow-up) and 3,816 adolescents (99% of those in follow-up). The study
      characterizes the data collection methodology in more than 7,000 individuals and
      discusses issues in its implementation. It thus provides a methodological
      framework aimed at helping to plan future population-based studies with the use
      of such technology and to improve understanding of physical activity in the
      context of epidemiological studies.

PMID- 23532291
TI  - [Association between marital status and mortality among elderly residents in Sao
      Paulo City, Brazil, SABE Study, 2000 and 2006].
AB  - This study aimed to analyze the association between mortality and marital status
      in the elderly population (60 years and older) in Sao Paulo, Brazil. The authors
      used data from the SABE Study (Health, Well-Being, and Aging) from 2000 and 2006.
      Statistical analysis used Poisson regression, considering variation in time of
      mortality risk. The mortality rate among single elderly males was 61% higher than
      among married men. Separation or divorce and widowhood increased the odds of
      death in elderly women (separated/divorced women and widows showed mortality
      rates 82% and 35% higher, respectively, than married women). It is hoped that the
      current study will improve our understanding of factors associated with survival
      in the elderly, in addition to supporting health policies for this population
      group.

PMID- 23532292
TI  - [Rubella vaccination in women of childbearing age in Campinas, Sao Paulo State,
      Brazil].
AB  - Women of reproductive age are the population of greatest interest for the
      prevention of congenital rubella syndrome. The aim of this study was to evaluate
      the prevalence of rubella vaccination in women and to identify factors associated
      and motives for non-adherence. A cross-sectional population-based study, in
      Campinas, Sao Paulo State, Brazil, in 2008/2009, was carried out with stratified
      random, two-stage cluster sampling. Of the 778 women aged 10 to 49 years, 83.8%
      (95%CI: 79.6-88.0) reported vaccination in life. Age group (20-39 years), per
      capita household income greater than 3 times the minimum wage and orientation of
      health care professionals about the vaccine, were positively associated with
      rubella vaccination. The main motives for non-adherence were lack of orientation
      of professionals about their importance (48.5%) and not consider it necessary
      (18.9%). The recommendation of professionals was the factor most strongly
      associated with women's adherence to vaccination. In this sense, an indication of
      vaccination by health care teams can increase the knowledge about the importance
      their and benefits.

PMID- 23532293
TI  - Circulatory disease mortality rates in the elderly and exposure to PM(2.5)
      generated by biomass burning in the Brazilian Amazon in 2005.
AB  - The aim of this study was to analyze the association between the exposure to fine
      particulate matter and circulatory disease mortality rates in the elderly living
      in the Brazilian Amazon. An ecological study of circulatory disease, acute
      myocardial infarction and cerebrovascular disease mortality rates in micro areas
      of the Brazilian Amazon was carried out. The environmental exposure indicator
      used was percentage hours of PM(2.5) concentrations > 25ug/m(3) divided by the
      total number of estimated hours of PM(2.5) in 2005. The association between
      exposure and circulatory disease mortality rates was strongest in the oldest age
      group. No significant statistical association was found between cerebrovascular
      disease mortality rates and exposure. Circulatory disease mortality rates in the
      elderly living in the Amazon have been influenced by atmospheric pollution from
      emissions caused by forest fires.

PMID- 23532294
TI  - Cervical cancer mortality trends in Brazil: 1980-2009.
AB  - The objective was to describe time trends in cervical cancer mortality rates in
      Brazil as a whole and in the country's major geographic regions and States from
      1980 to 2009. This was an ecological time series study using data recorded in the
      Mortality Information System (SIM) and census data collected by the Brazilian
      Institute of Geography and Statistics (IBGE). Analysis of mortality trends was
      performed using Poisson regression. Cervical cancer mortality rates in Brazil
      tended to stabilize. In the geographic regions, a downward trend was observed in
      the South (-4.1%), Southeast (-3.3%), and Central-West (-1%) and an upward trend
      in the Northeast (3.5%) and North (2.7%). The largest decreases were observed in
      the States of Sao Paulo (-5.1%), Rio Grande do Sul, Espirito Santo, and Parana (
      4.0%). The largest increases in mortality trends occurred in Paraiba (12.4%),
      Maranhao (9.8%), and Tocantins (8.9%). Cervical cancer mortality rates stabilized
      in the country as a whole, but there was a downward trend in three geographic
      regions and 10 States, while two geographic regions and another 10 States showed
      increasing rates.

PMID- 23532295
TI  - Sexual and reproductive health of women living with HIV in Southern Brazil.
AB  - This cross-sectional study focused on the sexual and reproductive health of women
      living with HIV, by age group, in the city of Porto Alegre, Rio Grande do Sul
      State, Brazil. The sample consisted of 691 women. Differences were observed in
      number of pregnancies and number of children. History of illicit drug use was
      more frequent in the 18-34-year age group, and exchanging sex for money was more
      frequent among women 18-29 years of age. This sample of women living with HIV
      treated in specialized public services in Southern Brazil showed a socioeconomic
      profile and sexual behavior that did not match the pattern typically identified
      in the process of "feminization" of the epidemic (with a majority of poor women
      with low schooling and a limited number of sexual partners). The study provides
      evidence of factors characterizing women's vulnerability to HIV infection,
      differing by age and raising specific demands for healthcare services.

PMID- 23532296
TI  - [First stage of the cross-cultural adaptation of the instrument The Vulnerable
      Elders Survey (VES-13) to Portuguese].
AB  - The aim of this study was to describe the initial stages of the cross-cultural
      adaptation of the instrument The Vulnerable Elders Survey (VES-13) for use in the
      context of cancer care in Brazil. Two translations into Portuguese and two back
      translations into English were carried out independently, and a formal assessment
      of the general and referential meanings was performed in order to obtain a
      synthesis version. Understanding of the synthesis version was evaluated in a
      pretest applied to 33 patients in an oncologic hospital of the Brazilian Unified
      National Health System (SUS). The version was easily applied in the intended
      context and was well-accepted by elders. The Portuguese version of the VES-13
      proved to be well understood and adequate for testing its psychometric qualities.
      The latter step is currently in the final phase.

PMID- 23532298
TI  - Early management of type 2 diabetes based on a SMBG strategy: the way to diabetes
      regression--the St Carlos study : a 3-year, prospective, randomized, clinic
      based, interventional study with parallel groups.
AB  - The aims are to define the regression rate in newly diagnosed type 2 diabetes
      after lifestyle intervention and pharmacological therapy based on a SMBG (self
      monitoring of blood glucose) strategy in routine practice as compared to standard
      HbA1c-based treatment and to assess whether a supervised exercise program has
      additional effects. St Carlos study is a 3-year, prospective, randomized, clinic
      based, interventional study with three parallel groups. Hundred and ninety-five
      patients were randomized to the SMBG intervention group [I group; n = 130; Ia:
      SMBG (n = 65) and Ib: SMBG + supervised exercise (n = 65)] and to the HbA1c
      control group (C group) (n = 65). The primary outcome was to estimate the
      regression rate of type 2 diabetes (HbA1c <6 % on metformin treatment). After 3
      years of follow-up, diabetes regression was achieved by 56 patients, 6 (9.2 %)
      from the C group, 21 (32.3 %) from the Ia group and 29 (44.6 %) from the Ib
      group. RR (95 % CI) for diabetes regression in the intervention group (Ia + Ib)
      was 4.5 (2.1-9); p < 0.001 and remained after stratification by gender, age and
      BMI. This difference was associated with healthier changes in lifestyle and
      greater weight loss. RR for a weight loss >4 kg was 3.6 (1.8-7); p < 0.001. This
      study shows that the use of SMBG in an educational program effectively increases
      the regression rate in newly diagnosed type 2 diabetic patients after 3 years of
      follow-up. These data suggest that SMBG-based programs should be extended to
      primary care settings where diabetic patients are usually attended.

PMID- 23532299
TI  - MicroRNA genetic variations: association with type 2 diabetes.
AB  - MicroRNAs are small single-stranded molecules that have emerged as important
      genomic regulators in different pathways. Different studies have shown that they
      are implicated in the metabolism and glucose homeostasis, and therefore, they
      could also be involved in the pathogenesis of metabolic disorders such as type 2
      diabetes (T2DM). The aim of this study was to verify whether genetic variations
      in candidate microRNA (miRNA or miR) genes could contribute to T2DM
      susceptibility. We have selected 13 miRNAs as candidate loci according to
      literature data and to a computational analysis. MicroRNA genes were analyzed by
      direct sequencing in a cohort of 163 Italian T2DM patients and 185 healthy
      controls. We identified 6 novel variants never described before and 9 SNPs
      already described in databases. Five newly identified variants were found only in
      the cases group. We performed a case/control association study to test the
      associations of particular alleles/genotypes of identified SNPs with the disease.
      Two polymorphisms were associated with T2DM susceptibility: in particular, the G
      allele of rs895819 in hsa-mir-27a has shown a significantly protective effect (OR
      = 0.58 and P = 0.008), while the G allele of rs531564 in hsa-mir-124a appears to
      be a risk allele (OR = 2.15, P = 0.008). This is the first report indicating that
      genetic polymorphisms in miRNA regions could contribute to T2DM susceptibility.

PMID- 23532301
TI  - Dynamic versus rigid stabilization for the treatment of disc degeneration in the
      lumbar spine.
AB  - STUDY DESIGN:  Retrospective cohort study. CLINICAL QUESTION:  This study aimed
      to describe the outcome of stabilization surgery with dynamic instrumentation for
      degenerative disc disease. The results were compared with age- and gender-matched
      peers treated with traditional fusion with rigid instrumentation. If necessary,
      additional nerve elements decompression was undertaken in both groups. METHODS: 
      This study analyzed the success rates of 25 patients aged 47.4 years (mean 95%
      confidence interval: 43.1-51.7) treated with stabilization of the involved
      vertebral dynamic unit(s) with either dynamic or rigid instrumentation with or
      without additional decompression. Clinical outcome was assessed with Oswestry
      disability index (ODI) and visual analogue scale (VAS) for back pain, leg pain,
      and activity level. Satisfaction outcome was measured with Stauffer and Coventry
      overall satisfaction criteria and VAS for satisfaction. Health-related quality of
      life was estimated with Short Form-36 (SF-36) questionnaires. Fusion rate and
      adjacent level(s) was checked with x-ray. Complications recorded in patients'
      files were evaluated and revision surgeries were stated as treatment failures.
      RESULTS:  At the 4-year follow-up (range, 2-5 years) significant improvement was
      noted on some subjective parameters in both groups. No statistical differences
      were seen between the groups at final follow-up. Five patients (42%) in the rigid
      group and two patients (20%) in the dynamic group were rated good or excellent
      according to the overall Stauffer and Coventry satisfaction criteria.
      Radiologically, seven patients (58%) in the rigid group were undoubtedly fused
      and all the involved discs in the dynamic group continued to degenerate. Adjacent
      segments showed loss of disc height in both groups but only loss of upper
      adjacent discs in the rigid group was statistically significant. Two patients in
      the dynamic group and one patient in the rigid group required reoperation because
      of the pedicle screw misplacement. CONCLUSION:  The results of this study
      indicate no significant difference between dynamic and rigid stabilization of the
      lumbar spine for patients with degenerative disc disease (DDD). However, the
      study is underpowered and further studies on larger and homogeneous group of
      patients should be undertaken. [Table: see text].

PMID- 23532300
TI  - Role of nonoperative treatment in managing degenerative tears of the medial
      meniscus posterior root.
AB  - BACKGROUND: Tears of the medial meniscus posterior root can lead to progressive
      arthritis, and its management has no consensus. The aim of our study was to
      evaluate the effect of supervised exercise therapy on patients with medial
      meniscus posterior root tears. MATERIALS AND METHODS: Between January 2005 and
      May 2007, 37 patients with this tear verified by magnetic resonance imaging (MRI)
      and osteoarthritis grade 1-2 by radiographic examination were treated by a short
      course of analgesics daily for up to 6 weeks and then as required during follow
      up, as well as a 12-week supervised exercise program followed by a home exercise
      program. Final analysis was performed for 33 patients, average age 55.8 (range 50
      62) years and average follow-up of 35 (range 26-49) months. Patients were
      followed up at 3, 6, and 12 months and yearly thereafter using the Lysholm Knee
      Scoring Scale, Tegner Activity Scale (TAS), and visual analog scale (VAS). The
      analysis was performed using one-way analysis of variance (ANOVA) and Pearson's
      correlation coefficient to determine the relationship between Lysholm score and
      body mass index (BMI). RESULTS: Patients showed an improvement in Lysholm score,
      TAS, and VAS, which reached maximum in 6 months and later was accompanied by a
      decline. However, scores at the final follow-up were significantly better than
      the pretherapy scores. There was also a progression in arthritis as per Kellgren
      and Lawrence radiographic classification from median 1 preintervention to median
      2 at the final follow-up. A correlation between BMI and Lysholm scores was seen
      (r = 0.47). CONCLUSION: Supervised physical therapy with a short course of
      analgesics followed by a home-based program results in symptomatic and functional
      improvement over a short-term follow-up; however, osteoarthritis progression
      continues and is related to BMI.

PMID- 23532302
TI  - Molecular dynamic simulations of the tubulin-human gamma synuclein complex:
      structural insight into the regulatory mechanism involved in inducing resistance
      against Taxol.
AB  - Members of the synuclein family (alpha, beta and gamma synucleins) are
      intrinsically disordered in nature and play a crucial role in the progression of
      various neurodegenerative disorders and cancers. The association of gammaSyn with
      both BubR1 as well as microtubule subunits renders resistance against various
      anti-cancer drugs. However, the structural aspects underlying drug resistance
      have not been explored. In this study, the mechanism involved in the association
      between gammaSyn and microtubule subunits (alphabetaTub) was investigated and the
      results reveal a strong interaction between gammaSyn and the tail regions of
      alphabetaTub. Complexation of gammaSyn induces conformational rearrangements in
      the nucleotide binding loops (NBL), interdomain and tail regions of both alpha
      and betaTub. Moreover, in betaTub, the massive displacement observed in M and S
      loops significantly alters the binding site of microtubule targeting drugs like
      Taxol. The resulting weak association between Taxol and betaTub of the gammaSyn
      alphabetaTub complex was confirmed by molecular dynamic simulation studies. In
      addition, the effect of Taxol on NBL, M and S loops of alphabetaTub, is reversed
      in the presence of gammaSyn. These results clearly indicate that the presence of
      gammaSyn annulled the allosteric regulation imposed by Taxol on the alphabetaTub
      complex as well as preventing the binding of microtubule targeting drugs, which
      eventually leads to the development of resistance against these drugs in cancer
      cells.

PMID- 23532297
TI  - Hormone interactions in xylem development: a matter of signals.
AB  - Xylem provides long-distance transport of water and nutrients as well as
      structural support in plants. The development of the xylem tissues is modulated
      by several internal signals. In the last decades, the bloom of genetic and
      genomic tools has led to increased understanding of the molecular mechanisms
      underlying the function of the traditional plant hormones in xylem specification
      and differentiation. Critical functions have been assigned to novel signaling
      molecules, such as thermospermine. These signals do not function independently,
      but interact in a manner we are only now beginning to understand. We review the
      current knowledge of hormone signaling pathways and their crosstalk in cambial
      cell initiation and maintenance, and in xylem specification and differentiation.

PMID- 23532303
TI  - Thermal tolerance, oxygen consumption and haemato-biochemical variables of Tor
      putitora juveniles acclimated to five temperatures.
AB  - A 30-day acclimation trial was conducted using Tor putitora to elucidate its
      thermal tolerance, oxygen consumption, haemato-biochemical variables and selected
      enzymatic activities at five acclimation temperatures (AT). Juveniles of T.
      putitora were randomly distributed among five treatment groups (20, 23, 26, 29
      and 32 +/- 0.5  degrees C). There was a significant curvilinear increase in
      critical thermal maxima (CT(max)) (y = -0.0693x2 + 1.7927x + 34.628, R2 = 0.996)
      and lethal thermal maxima (LT(max)) (y = -0.1493x2 + 2.3407x + 35.092, R2 =
      0.991) with increasing AT. The oxygen consumption rate increased significantly
      with increasing AT. The Q10 values were 1.16 between 20 and 23  degrees C, 3.09
      between 23 and 26  degrees C, 1.31 between 26 and 29  degrees (C) and 1.76
      between 29 and 32  degrees C of AT. The acclimation response ratios were ranged
      between 0.37 and 0.59. Catalase, superoxide dismutase and ATPase activities were
      increased linearly in liver, gill and kidney, while brain acetylcholine esterase
      activity decreased linearly with increasing AT. Blood glucose remained unchanged
      up to AT of 26  degrees C and increased significantly at AT of 29 and 32  degrees
      C. Haemoglobin content was increased linearly with increasing AT. The highest WBC
      count was observed at 20  degrees C, and no significant changes found till AT of
      26  degrees C and significantly decreased at 32  degrees C. Total serum protein
      and globulin were significantly decreased with increasing AT. Highest values were
      observed at 20  degrees C and remained consistent till 26  degrees C, then
      decreased significantly. There was no significant change in A/G ratio through the
      AT 20-29  degrees C and increased significantly at 32  degrees C. The increase in
      CT(max), LT(max) and oxygen consumption rate with increasing AT may suggest that
      the thermal tolerance of T. putitora is dependent on its prior thermal exposure
      history, and it could adapt to higher AT by altering its haemato-biochemical
      variables.

PMID- 23532304
TI  - Establishment and characterization of a fin cell line from blunt snout bream,
      Megalobrama amblycephala.
AB  - This study established and characterized a new cell line (MAF) from the fin of
      blunt snout bream (Megalobrama amblycephala), a freshwater fish cultivated in
      China. MAF cells proliferated well in medium 199 supplemented with 10 % fetal
      bovine serum at 28  degrees C and have been subcultured more than 95 times in
      almost a year. MAF cells were revived at 90-95 % viability after 3-6 months of
      storage in liquid nitrogen. Karyotyping indicated that the modal chromosome
      number of MAF cells was 48. The MAF cell line consisted predominantly of
      fibroblastic and epithelial-like cells from M. amblycephala, which was confirmed
      by immunofluorescence and mitochondrial 12s rRNA sequencing. Viral susceptibility
      tests showed that MAF cells were susceptible to infection by snakehead
      rhabdovirus, spring viremia carp virus, and channel catfish virus, which was
      demonstrated by the presence of cytopathic effect, high viral titers, and PCR
      products. Bacterial cytotoxicity studies showed that extracellular products from
      Aeromonas hydrophila were toxic to MAF cells. Cu2+ was also cytotoxic to MAF
      cells, and the 24-h IC50 value was 144.48 MUmol/l. When MAF cells were
      transfected with pEGFP-N1 plasmid, bright fluorescent signals were observed, and
      the transfection efficiency reached up to 5 %. These results suggest that the MAF
      cell line may provide a valuable tool for studying virus pathogenesis, as well as
      cytotoxicity testing and genetic manipulation studies.

PMID- 23532305
TI  - Cost-of-illness analysis of patients with chronic hand eczema in routine care in
      Germany: focus on the impact of occupational disease.
AB  - Chronic hand eczema places a heavy burden on patients, often affecting their
      ability to work. This paper compares the cost-of-illness and treatment approaches
      for patients with refractory chronic hand eczema, in relation to whether the
      disease was occupational or unrelated to work factors. Data from 2 surveys,
      comprising 310 patients with chronic hand eczema insured by German statutory
      health insurance (SHI) (including work-impaired patients, work-unaffected
      patients and non-working patients) and known work-related chronic hand eczema
      insured by occupational health insurance (OHI). Annual healthcare costs of
      managing work-impaired patients (SHI) and patients with work-related chronic hand
      eczema (OHI) were ?3,164 and ?3,309, respectively, approximately double the costs
      of managing non-working and work-unaffected (SHI) patients. This analysis shows
      that the costs associated with chronic hand eczema are affected by the
      correlation of chronic hand eczema with work, with costs being higher for
      occupational patients with chronic hand eczema. 

PMID- 23532306
TI  - Remote ischemic preconditioning in hemodialysis: a pilot study.
AB  - Hemodialysis (HD)-induced myocardial ischemia is associated with an elevated
      cardiac troponin T, and is common in asymptomatic patients undergoing
      conventional HD. Remote ischemic preconditioning (RIPC) has a protective effect
      against myocardial ischemia-reperfusion injury. We hypothesized that RIPC also
      has a protective effect on HD-induced myocardial injury. Chronic HD patients were
      randomized to the control group or the RIPC group. RIPC was induced by transient
      occlusion of blood flow to the arm with a blood-pressure cuff for 5 min, followed
      by 5 min of deflation. Three cycles of inflation and deflation were undertaken
      before every HD session for 1 month (total 12 times). The primary outcome was the
      change in cardiac troponin T (cTnT) level at day 28 from baseline. Demographic
      and baseline laboratory values were not different between the control (n = 17)
      and the RIPC groups (n = 17). cTnT levels tended to decrease from day 2 in the
      RIPC group through to 28 days, in contrast to no change in the control group.
      There were significant differences in the change of cTnT level at day 28 from
      baseline [Control, median; -0.002 ng/ml (interquartile range -0.008 to 0.018)
      versus RIPC, median; -0.015 ng/ml (interquartile range -0.055 to 0.004), P =
      0.012]. RIPC reduced cTnT release in chronic conventional HD patients, suggesting
      that this simple, cheap, safe, and well-tolerated procedure has a protective
      effect against HD-induced ischemia. 

PMID- 23532307
TI  - Serum tenascin-C level is associated with coronary plaque rupture in patients
      with acute coronary syndrome.
AB  - Tenascin-C, a large oligometric glycoprotein of the extracellular matrix,
      increases the expression of matrix metalloproteinases that lead to plaque
      instability and rupture, resulting in acute coronary syndrome (ACS). We
      hypothesized that a high serum tenascin-C level is associated with plaque rupture
      in patients with ACS. Fifty-two consecutive ACS patients who underwent emergency
      percutaneous coronary intervention (PCI) and, as a control, 66 consecutive
      patients with stable angina pectoris (SAP) were enrolled in this study. Blood
      samples were obtained from the ascending aorta just prior to the PCI procedures.
      After coronary guide-wire crossing, intravascular ultrasonography (IVUS) was
      performed for assessment of plaque characterization. Based on the IVUS findings,
      ACS patients were assigned to two groups according to whether there was ruptured
      plaque (ruptured ACS group) or not (nonruptured ACS group). There were 23
      patients in the ruptured group and 29 patients in the nonruptured group. Clinical
      characteristics and IVUS measurements did not differ between the two groups.
      Tenascin-C levels were significantly higher in the ruptured ACS group than in the
      SAP group, whereas there was no significant difference between the nonruptured
      ACS and SAP groups. Importantly, in the ruptured ACS group, tenascin-C levels
      were significantly higher than in the nonruptured ACS group (71.9 +/- 34.9 vs
      50.5 +/- 20.5 ng/ml, P < 0.005). Our data demonstrate that tenascin-C level is
      associated with pathologic conditions in ACS, especially the presence of ruptured
      plaque. 

PMID- 23532308
TI  - Novel structure--function information on biogenic amine transporters revealed by
      site-directed mutagenesis and alkylation.
AB  - The study reported by Wenge and Bonisch in this issue provides critical
      structural information regarding extracellular loop 2 (EL2) of the human
      norepinephrine transporter (NET). A systematic search among all 10 cysteine and
      13 histidine residues in NET led to His222 in EL2 as the target for N
      ethylmaleimide: its alkylation interferes with [(3)H]nisoxetine binding,
      indicating the part of EL2 containing His 222 reaches back into the protein
      interior where it prevents access by nisoxetine to its binding site. Thus, EL2 in
      human NET does much more than conformationally assisting substrate translocation.
      The present study underscores the importance of site-directed mutagenesis
      approaches to elucidate structural features that cannot be deduced from crystals
      of homolog proteins. In the case of NET, the closest crystal structure is that of
      the homolog LeuT, but EL2 is difficult to align with 22 less loop residues in
      LeuT than in NET. The present results could only be achieved by the systematic
      mutagenesis study of all cysteines and all histidines in NET.

PMID- 23532309
TI  - [Health and development: a new approach for a new policy].

PMID- 23532310
TI  - [The innovative dynamic of the mechanics, electronics and materials subsystem].
AB  - The mechanics, electronics and materials subsystem, one of the subsystems of the
      health care productive complex, encompasses different activities, usually
      clustered in what is called the medical, hospital and dental equipment and
      materials industry. This is a strategic area for health care, since it represents
      a continuous source of changes in care practices, and influences the provision of
      health care services. It has, moreover, potential for promoting the progress of
      Brazil's system of innovation and for increasing the competitiveness of the
      industry as a whole, given that it articulates future technologies. Despite the
      significant growth of this industry in Brazil in recent years, such equipment and
      materials have been presenting a growing deficit in the balance of trade. This
      incompatibility between national health care needs and the productive and
      innovative basis of the industry points to structural fragilities in the system.
      Using the framework of political economy, the article aims to discuss the
      development of this industry in Brazil and its challenges.

PMID- 23532311
TI  - [Innovation in pharmaceutical and health biotechnology industries: challenges for
      a virtuous agenda].
AB  - Pharmaceutical and biotechnology industries comprise a major production subsystem
      of the health industrial complex in Brazil. It stands out for both its economic
      importance and its prominent role in developing new technologies in strategic
      areas. Strengthening the local production of generic drugs in the last decade has
      significantly increased the number of Brazilian companies in the local
      pharmaceutical market and has been an important turning point for this industry's
      growth. However, there remain major structural bottlenecks both in terms of
      production and continuous innovation. These bottlenecks reveal the high
      vulnerability of the Brazilian National Health System and point to the need of
      public policies that promote strengthening the production base and innovation in
      the pharmaceutical industry and that at the same time meet health-related social
      demands in health in Brazil.

PMID- 23532312
TI  - [Health-related scientific and technological capabilities and university-industry
      research collaboration].
AB  - OBJECTIVE: To examine recent developments in health-related scientific
      capabilities, the impact of lines of incentives on reducing regional scientific
      imbalances, and university-industry research collaboration in Brazil. METHODS:
      Data were obtained from the Conselho Nacional de Desenvolvimento Cientifico e
      Tecnologico (Brazilian National Council for Scientific and Technological
      Development) databases for the years 2000 to 2010. There were assessed indicators
      of resource mobilization, research network structuring, and knowledge transfer
      between science and industry initiatives. RESULTS: Based on the regional
      distribution map of health-related scientific and technological capabilities
      there were identified patterns of scientific capabilities and science-industry
      collaboration. There was relative spatial deconcentration of health research
      groups and more than 6% of them worked in six areas of knowledge areas: medicine,
      collective health, dentistry, veterinary medicine, ecology and physical
      education. Lines of incentives that were adopted from 2000 to 2009 contributed to
      reducing regional scientific imbalances and improving preexisting capabilities
      or, alternatively, encouraging spatial decentralization of these capabilities.
      CONCLUSIONS: Health-related scientific and technological capabilities remain
      highly spatially concentrated in Brazil and incentive policies have contributed
      to reduce to some extent these imbalances.

PMID- 23532313
TI  - [The innovative dynamics for the restructuring of the health services].
AB  - Challenges posed by demographic and epidemiological changes and by the need to
      reduce costs have required the restructuring of the health services. Health
      innovations play a major role in this process, as technologies are fundamental
      both to expand the access and to adapt the system to the population's needs.
      However, the generation of health innovation is not based solely on sanitary
      demands and conditioning factors; on the contrary, it often reflects a trajectory
      of development and the interests of restricted groups in society. These issues
      need to be taken into consideration both in the analysis of the complexity of the
      health dimensions and in the investigation of the potential and challenges for
      the establishment of a virtuous innovative dynamics for the restructuring of the
      health services.

PMID- 23532314
TI  - [Chronic non-communicable diseases in Brazil: priorities for disease management
      and research].
AB  - Chronic Non-Communicable Diseases are the main source of disease burden in
      Brazil. In 2011, the Brazilian Ministry of Health launched the Strategic Plan of
      Action for Management of Chronic Non-Communicable Diseases focusing on population
      based interventions to manage cardiovascular diseases, diabetes, cancer, and
      chronic respiratory diseases mainly through fighting tobacco use, unhealthy
      diets, physical inactivity and the harmful use of alcohol. Although a significant
      number of scientific studies on chronic diseases and their risk factors have been
      undertaken in Brazil, few are of cohort design. In this context, the Brazilian
      Longitudinal Study of Adult Health (ELSA-Brasil), a cohort study of 15,105
      Brazilian public servants reflects the reality of high prevalences of diabetes,
      hypertension and the main chronic diseases risk factors. The diversity of
      information that the Study will produce can provide important input to better
      understand the causes of chronic diseases and to support public policies for
      fighting them.

PMID- 23532315
TI  - Predicting non-invasive ventilation failure in children from the SpO2/FiO2 (SF)
      ratio.
AB  - PURPOSE: Our objective was to assess whether SpO2/FiO2 (SF) ratio could be a
      useful NIV outcome predictor in children with acute respiratory failure (ARF) and
      tried to develop a predictive model of NIV failure. METHODS: Prospective,
      observational, multicenter study. Episodes of ARF-fulfilling inclusion criteria
      from 15 January 2010 to 14 January 2011 were treated with NIV according to a pre
      established protocol. Clinical variables were collected at baseline and at 1, 2,
      6, 12 and 24 h. Failure criterion was the need for endotracheal intubation.
      Failures were considered as "early" if occurring <=6 h after NIV initiation,
      "intermediate" if occurring between 6 and 24 h, and "late" if occurring after 24
      h. Variables with a p < 0.1 in univariate analysis corrected by age were included
      in multivariate analysis. Models were calculated based on multivariate analysis.
      RESULTS: During the study period, 390 episodes were included. NIV success rate
      was 81.3 %. Among ARF causes, failure occurred most frequently in ARDS episodes.
      The failure predictive model for the whole sample included SF ratio at 1 h, age
      and PRISM III-24 (area under the curve AUC of 0.755). For early NIV failures, SF
      ratio at 1 h was the only variable within model (AUC 0.748). The analysis of
      intermediate NIV failures identified 3 variables independently linked to NIV
      outcome: PRISM III-24, RR decrease at 6 h, and SF ratio at 6 h (AUC 0.895). No
      model was identified for late NIV failure. CONCLUSIONS: SF ratio is a reliable
      predictor of early NIV failure in children.

PMID- 23532316
TI  - Production of natural value-added compounds: an insight into the eugenol
      biotransformation pathway.
AB  - During the past few years, the production of natural value-added compounds from
      microbial sources has gained tremendous importance. Due to an increase in
      consumer demand for natural products, various food and pharmaceutical industries
      are continuously in search of novel metabolites obtained from microbial
      biotransformation. The exploitation of microbial biosynthetic pathways is both
      feasible and cost effective in the production of natural compounds. The
      environmentally compatible nature of these products is one major reason for their
      increasing demand. Novel approaches for natural product biogeneration will take
      advantage of the current studies on biotechnology, biochemical pathways and
      microbiology. The interest of the scientific community has shifted toward the use
      of microbial bioconversion for the production of valuable compounds from natural
      substrates. The present review focuses on eugenol biotransformation by
      microorganisms resulting in the formation of various value-added products such as
      ferulic acid, coniferyl alcohol, vanillin and vanillic acid.

PMID- 23532317
TI  - Sporicidal efficacy of pH-adjusted bleach for control of bioburden on production
      facility surfaces.
AB  - pH-adjusted bleach was one of the agents used to disinfect contaminated public
      buildings in the USA following the 2001 bioterrorist attack with Bacillus
      anthracis spores. A USEPA fact sheet describes the preparation of pH-adjusted
      bleach by combining diluted sodium hypochlorite (NaOCl) with a controlled amount
      of 5 % acetic acid. This paper reports a modification of this procedure to
      qualify the use of pH-adjusted bleach for routine disinfection of cleanroom
      surfaces in pharmaceutical manufacturing facilities whenever a short contact time
      is desirable or there is a need for enhanced germicidal or sporicidal activity.
      Adjustment of pH was obtained reproducibly with either acetic acid or HCl,
      confirming the feasibility of developing standard procedures for the controlled
      addition of acid to diluted NaOCl solutions without compromising operator safety
      and convenience. Efficacy testing using spores from an in-house isolate of
      Bacillus pumilus confirmed that NaOCl solutions in the pH 5-8 range have much
      greater sporicidal activity on surfaces than do unadjusted alkaline solutions (pH
      > 11). With a contact time of 0.5 min, the log10 reduction in spore viable counts
      was >5.4 for the five representative surfaces tested relative to untreated
      controls. Solutions of pH-adjusted NaOCl are known to be less stable than
      unadjusted alkaline solutions. Stability studies were performed by monitoring
      sporicidal efficacy, level of free available chlorine (FAC), and pH. Testing
      included several NaOCl concentrations and adjustment to different starting pHs.
      The efficacy of pH-adjusted solutions persisted in open containers for at least
      12 h even though some FAC degradation occurred. In addition, solutions of 0.29 or
      0.50 % NaOCl stored at room temperature protected from light retained efficacy
      for at least 4 weeks, indicating that short-term storage of solutions is possible
      following pH adjustment. The inorganic chemical degradation of pH-adjusted NaOCl
      solutions generates chlorate ion, an undesirable by-product. A comparison of
      chemical stability for 0.12, 0.25, and 0.50 % NaOCl solutions adjusted to
      different initial pHs indicated that the least chlorate formation occurred with
      0.12 % NaOCl.

PMID- 23532318
TI  - Rare earth complexes of phenoxy-thioether ligands: synthesis and reactivity in
      the ring opening polymerization of cyclic esters.
AB  - The potential of the phenoxy-thioether moieties as ancillary ligands in the
      coordination chemistry of group 3 metals was explored. The amine elimination
      reactions between yttrium and scandium amido precursors {M [N(SiHMe2)2]3 (THF)n}
      with the proligands {4,6-tBu2-OC6H2-2-CH2S(2-R-C6H4)}H [R = H (L1-H), CH3 (L2-H),
      Br (L3-H), CF3 (L4-H)], bearing different substituents at the ortho position of
      the thiophenol aryl ring, were studied. The outcome of aminolysis reactions gave
      different results depending on the structure of the proligand and the reaction
      conditions. Heteroleptic scandium and yttrium amido complexes with general
      formula {(L)2M [N(SiHMe2)2] (THF)n} were prevailingly obtained from phenoxy
      thioether proligands L1-H and L4-H. In contrast, homoleptic yttrium complexes
      bearing three phenoxy-thioether ligands were favored with L2-H and L3-H. The
      activities of all the synthesized complexes toward the ring-opening
      polymerization of epsilon-caprolactone and L- and rac-lactide were investigated,
      also in combination with an alcohol as an external chain transfer agent.
      Polyesters with controlled molecular parameters (Mn, end groups) and low
      polydispersities were obtained. The monoinsertion adduct, produced by the
      reaction of {(L1)2ScN(SiHMe2)2} and 1 equiv. of epsilon-caprolactone, was
      isolated proving that a coordination-insertion mechanism of ring-opening
      polymerization was operative. In the polymerization of rac-lactide, yttrium
      complexes exerted a high degree of stereocontrol producing heterotactic
      polylactides (P(r) up to 0.91).

PMID- 23532319
TI  - A comparative study of the redox and excited state properties of (nBu4N)2[Mo6X14]
      and (nBu4N)2[Mo6X8(CF3COO)6] (X = Cl, Br, or I).
AB  - The excited-state dynamics, luminescence, and redox properties of a series of
      hexanuclear molybdenum cluster complexes, (nBu4N)2[Mo6X14] and
      (nBu4N)2[Mo6X8(CF3COO)6] (X = Cl, Br, or I), were investigated. Substitution of
      the apical halogen ligands for the trifluoroacetate ligands increased the
      oxidation potentials and induced a blue shift in the absorption and luminescence
      bands as well as a considerable increase in the luminescence quantum yields for
      heavy inner ligands. Time-resolved transient absorption measurements showed that
      the intersystem crossing from the excited singlet states is ultrafast with time
      constants ranging between <120 fs and 1.68 ps and leads to hot triplet states.
      The following cooling occurred at a ps time scale and was assigned to electronic
      redistribution within the emissive triplet state sublevels. The formation of
      singlet oxygen, O2((1)Deltag), suggested earlier on the basis of photooxidation
      experiments for some complexes, was revised by direct measurements of
      O2((1)Deltag) phosphorescence. We showed the effects of the attached ligands on
      key physico-chemical and photophysical parameters of the title complexes. The
      synthesis and structural characterisation of a new cluster complex,
      (nBu4N)2[Mo6Br8(CF3COO)6], completed the series. Our results demonstrated that
      the complexes with heavy inner ligands (Br, I) and apical trifluoroacetate
      ligands were photochemically and electrochemically stable, highly luminescent,
      and good sensitisers of O2((1)Deltag).

PMID- 23532320
TI  - Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT,
      nitric oxide and vein graft.
AB  - For vascular occlusive disease, an autologous vein graft is the most suitable
      conduit for arterial reconstruction. Intimal hyperplasia, resulting from the
      migration and proliferation of vascular smooth muscle cells, is a major obstacle
      to patency after vein grafting. The degree to which the function of nitric oxide
      (NO) in the vein graft is preserved has been reported to be associated with the
      magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in
      the vascular system and plays physiological roles in controlling the vascular
      tone. The subtype receptors contributing to the 5-HT-induced mechanical responses
      vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and
      so on). Recent studies have demonstrated that 5-HT induces vasoconstriction
      through the activation of 5-HT2A receptors in smooth muscle cells or
      vasodilatation through the activation of endothelial 5-HT1B receptors in arteries
      from various animals. However, the effects of 5-HT have not been clarified in
      grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins
      and then autogenous vein grafts. Next, we describe the effects of chronic in vivo
      administration of Rho-kinase inhibitors and 5-HT2A receptor antagonists, both of
      which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts.
      Further studies targeting 5-HT are required to evaluate its possible benefits for
      autologous vein grafts with respect to vasospasm, function, and patency. 

PMID- 23532322
TI  - Direct embryo tagging and identification system by attachment of
      biofunctionalized polysilicon barcodes to the zona pellucida of mouse embryos.
AB  - STUDY QUESTION: Is the attachment of biofunctionalized polysilicon barcodes to
      the outer surface of the zona pellucida an effective approach for the direct
      tagging and identification of cultured embryos? SUMMARY ANSWER: The results
      achieved provide a proof of concept for a direct embryo tagging system using
      biofunctionalized polysilicon barcodes, which could help to minimize the risk of
      mismatching errors (mix-ups) in human assisted reproduction technologies. WHAT IS
      KNOWN ALREADY: Even though the occurrence of mix-ups is rare, several cases have
      been reported in fertility clinics around the world. Measures to prevent the risk
      of mix-ups in human assisted reproduction technologies are therefore required.
      STUDY DESIGN, SIZE, DURATION: Mouse embryos were tagged with 10 barcodes and the
      effectiveness of the tagging system was tested during fresh in vitro culture
      (n=140) and after embryo cryopreservation (n = 84). Finally, the full-term
      development of tagged embryos was evaluated (n =105). PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Mouse pronuclear embryos were individually rolled over wheat
      germ agglutinin-biofunctionalized polysilicon barcodes to distribute them
      uniformly around the ZONA PELLUCIDA surface. Embryo viability and retention of
      barcodes were determined during 96 h of culture. The identification of tagged
      embryos was performed every 24 h in an inverted microscope and without embryo
      manipulation to simulate an automatic reading procedure. Full-term development of
      the tagged embryos was assessed after their transfer to pseudo-pregnant females.
      To test the validity of the embryo tagging system after a cryopreservation
      process, tagged embryos were frozen at the 2-cell stage using a slow freezing
      protocol, and followed in culture for 72 h after thawing. MAIN RESULTS AND THE
      ROLE OF CHANCE: Neither the in vitro or in vivo development of tagged embryos was
      adversely affected. The tagging system also proved effective during an embryo
      cryopreservation process. Global identification rates higher than 96 and 92% in
      fresh and frozen-thawed tagged embryos, respectively, were obtained when
      simulating an automatic barcode reading system, although these rates could be
      increased to 100% by simply rotating the embryos during the reading process.
      LIMITATIONS, REASONS FOR CAUTION: The direct embryo tagging developed here has
      exclusively been tested in mouse embryos. Its effectiveness in other species,
      such as the human, is currently being tested. WIDER IMPLICATIONS OF THE FINDINGS:
      The direct embryo tagging system developed here, once tested in human embryos,
      could provide fertility clinics with a novel tool to reduce the risk of mix-ups
      in human assisted reproduction technologies.

PMID- 23532321
TI  - Gossypol induces apoptosis in ovarian cancer cells through oxidative stress.
AB  - In the present work, metabolomic and redox proteomic analyses were carried out on
      an untreated- and gossypol-treated ovarian cancer cell line, SKOV3. Gossypol
      treatment resulted in cell death through oxidative stress. Metabolite analysis
      showed that gossypol induces a decrease of the cellular levels of GSH, aspartic
      acid, and FAD. Using a combination of double labeling and LC-MS-MS, we identified
      changes in thiol-redox states of 545 cysteine-containing peptides from 356
      proteins. The frequently occurring amino acid residue immediately before or after
      the cysteine in these peptides is the non-polar and neutral leucine, valine, or
      alanine. These redox sensitive proteins participate in a variety of cellular
      processes. We have characterized the redox-sensitive cysteine residues in PKM2,
      HSP60, malate dehydrogenase and other proteins that play important roles in
      metabolism homeostasis and stress responses. The three cysteine residues of HSP60
      exhibit different responses to gossypol treatment: an increase of thiol/disulfide
      ratio for the Cys447 residue due to a decrease of the cellular GSH level, and a
      decrease of thiol/disulfide ratios for Cys442 and Cys237 residues due to
      oxidation and sulfation. This study suggests that thiol/disulfide ratios are
      dependent on the level of cellular GSH. Our data provide a valuable resource for
      deciphering the redox regulation of proteins and for understanding gossypol
      induced apoptosis in ovarian cancer cells.

PMID- 23532323
TI  - Double uterus with obstructed hemivagina and ipsilateral renal agenesis: pelvic
      anatomic variants in 87 cases.
AB  - STUDY QUESTION: What are the anatomic variants (and their frequencies) of double
      uterus, obstructed hemivagina and ipsilateral renal agenesis? SUMMARY ANSWER:
      Most cases examined (72.4%) were of the classic anatomic variant of the Herlyn
      Werner-Wunderlich syndrome (with didelphys uterus, obstructed hemivagina and
      ipsilateral renal agenesis) but the 27.6% of cases are of a rare variant of the
      syndrome (with uterus septum or cervical agenesis), showing relevant clinical and
      surgical implications. WHAT IS KNOWN ALREADY: The extreme variability of anatomic
      structures involved in this syndrome (both uterus, cervico-vaginal and renal
      anomalies) is well known, even if a complete and uniform analysis of all its
      heterogeneous presentations in a large series is lacking. STUDY DESIGN, SIZE,
      DURATION: This is a retrospective study with 87 patients referred to our third
      level referral center between 1981 and 2011. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: We analyzed the laparoscopic and chart records of 87 women, who referred
      to our institute with double uterus, unilateral cervico-vaginal obstruction and
      ipsilateral renal anomalies. MAIN RESULTS: Sixty-three of 87 patients had the
      more classic variant of didelphys uterus with obstructed hemivagina; 10/87
      patients had septate bicollis uterus with obstructed hemivagina; 9/87 patients
      had bicornuate bicollis uterus with obstructed hemivagina; 4/87 patients had
      didelphys uterus with unilateral cervical atresia; 1/87 patients had bicornuate
      uterus with one septate cervix and unilateral obstructed hemivagina. LIMITATIONS:
      This is a retrospective study with a long enrolling period (30 years). WIDER
      IMPLICATIONS OF THE FINDINGS: New insights in the anatomic variants of this rare
      syndrome with their relevant surgical implications.

PMID- 23532324
TI  - Reply: Questions about the accuracy of polar body analysis for preimplantation
      genetic screening.

PMID- 23532325
TI  - Questions about the accuracy of polar body analysis for preimplantation genetic
      screening.

PMID- 23532326
TI  - Questions about the accuracy of polar body analysis for preimplantation genetic
      screening.

PMID- 23532327
TI  - Ocular higher-order aberration features 10 years after photorefractive
      keratectomy.
AB  - The aim of the present study is to re-evaluate the original cohort of patients
      who participated in the first photorefractive keratectomy (PRK) trial in the
      1990s, especially their optical performance. Forty-four eyes (24 patients) of the
      original cohort who underwent PRK using the NIDK EC-5000 excimer laser platform
      returned 10 years (range 9-14 years) postoperatively to have higher-order
      aberrations (HOAs) recorded. Wavefront aberrations were measured using Wavescan
      (VISX, Santa Clara, CA, USA) and calculated for 3- and 6-mm pupil size. The total
      RMS (the square root of the sum of squared Zernike coefficients) of higher-order
      wavefront error (3rd-6th radial order) and the Zernike coefficients, as well as
      the third-order (S 3) and fourth-order (S 4) aberrations, spherical aberrations
      and coma aberration values were analyzed. An independent sample t test was used
      for comparisons and a P value <0.05 was considered statistically significant. The
      mean RMS of higher-order wavefront values showed an increase but no significant
      difference in postoperative eyes compared to the control-matched normal level
      with the 6-mm pupil (HOA RMS: control group 0.31 +/- 0.12 MUm; 10-year post-PRK
      group 0.56 +/- 0.15 MUm; P = 0.141). The main contribution was the increase of
      spherical aberrations (Z 12) and spherical-like aberrations (S 4), which
      increased by fourfold and 2.5-fold, respectively, in the 10-year post-PRK group
      (control group Z 12 0.08 +/- 0.11 MUm, S 4 0.14 +/- 0.05 MUm; 10-year post-PRK
      group Z 12 0.35 +/- 0.15 MUm, S 4 0.37 +/- 0.14 MUm; P = 0.010*). Most increases
      of ocular HOAs induced by corneal refractive surgery are becoming extremely minor
      at 10 years postoperatively, closer to the corresponding preoperative amount. The
      largest increase was spherical and spherical-like aberrations, especially with a
      larger pupil size. 

PMID- 23532329
TI  - Atopic dermatitis and non-atopic hand eczema have similar negative impacts on
      quality of life: implications for clinical significance.

PMID- 23532330
TI  - Focus issue: From genomic mutations to oncogenic pathways.
AB  - This two-issue series focuses on how understanding how signaling pathways are
      altered in cancer cells can enable researchers to develop more effective
      therapies. Cancer is a pleiotropic disease. Tumor cells change over time and,
      even within a specific tumor, cells may have different mutations and dependencies
      on different signaling pathways for survival or for metastatic potential. New
      tools and technologies for genomic- or systems-level analysis, as well as
      conventional biochemistry and cell biology approaches, are revealing how
      signaling pathways contribute to cancer development, cancer evolution, and drug
      resistance.

PMID- 23532328
TI  - Preoperative cardiac risk assessment for noncardiac surgery in patients with
      heart failure.
AB  - The aging population and an epidemic of heart failure have led to an increasing
      volume of noncardiac surgical procedures being performed in patients with heart
      failure. Knowledge pertaining to perioperative risk stratification and management
      among this diverse and complex cohort of patients has therefore become
      increasingly important. Most available data regarding the management of patients
      with heart disease undergoing noncardiac surgery is specific to patients with
      ischemic heart disease, and focuses on the prevention of ischemia and its
      subsequent complications. This review instead specifically explores the available
      data regarding the epidemiology and outcomes of the surgical patient with heart
      failure, with a focus on risk stratification and perioperative management.

PMID- 23532331
TI  - Disrupting the scaffold to improve focal adhesion kinase-targeted cancer
      therapeutics.
AB  - Focal adhesion kinase (FAK) is emerging as a promising cancer target because it
      is highly expressed at both the transcriptional and translational level in cancer
      and is involved in many aspects of tumor growth, invasion, and metastasis.
      Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic
      function and not the large scaffold it creates that includes many oncogenic
      receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK
      scaffold is a feasible and promising approach for developing highly specific
      therapeutics that disrupt FAK signaling pathways in cancer.

PMID- 23532332
TI  - A Wnt-er migration: the confusing role of beta-catenin in melanoma metastasis.
AB  - Wnt signaling in melanoma is complex, requiring the coordinate expression of
      multiple players. Depending on the context of receptors and co-receptors that are
      present, Wnt proteins may signal through either canonical or noncanonical
      pathways. The role of beta-catenin in melanoma metastasis remains unclear;
      however, a new study points to the roles of Wnt5A and ARF6 in driving beta
      catenin expression and melanoma metastasis. Here, we discuss this finding and how
      it may help us define different subpopulations of melanoma cells that could have
      different outcomes, as well as different responses to therapy.

PMID- 23532333
TI  - BIM, PUMA, and the achilles' heel of oncogene addiction.
AB  - Cancer cells undergo extensive genetic and epigenetic rewiring to support the
      malignant phenotype, and yet cell survival and proliferation often remain
      dependent on one or a limited number of driver mutations. This is the concept of
      oncogene addiction, the elucidation of which has led to substantial progress in
      therapeutic interventions. However, because resistance mechanisms often emerge,
      explicating the pathways that connect therapeutic oncogene inactivation to the
      cell death machinery is critical to exploiting additional synthetic lethal
      opportunities.

PMID- 23532336
TI  - Kinase-substrate enrichment analysis provides insights into the heterogeneity of
      signaling pathway activation in leukemia cells.
AB  - Kinases determine the phenotypes of many cancer cells, but the frequency with
      which individual kinases are activated in primary tumors remains largely unknown.
      We used a computational approach, termed kinase-substrate enrichment analysis
      (KSEA), to systematically infer the activation of given kinase pathways from mass
      spectrometry-based phosphoproteomic analysis of acute myeloid leukemia (AML)
      cells. Experiments conducted in cell lines validated the approach and,
      furthermore, revealed that DNA-dependent protein kinase (DNA-PK) was activated as
      a result of inhibiting the phosphoinositide 3-kinase (PI3K)-mammalian target of
      rapamycin (mTOR) signaling pathway. Application of KSEA to primary AML cells
      identified PI3K, casein kinases (CKs), cyclin-dependent kinases (CDKs), and p21
      activated kinases (PAKs) as the kinase substrate groups most frequently enriched
      in this cancer type. Substrates phosphorylated by extracellular signal-regulated
      kinase (ERK) and cell division cycle 7 (CDC7) were enriched in primary AML cells
      that were resistant to inhibition of PI3K-mTOR signaling, whereas substrates of
      the kinases Abl, Lck, Src, and CDK1 were increased in abundance in inhibitor
      sensitive cells. Modeling based on the abundances of these substrate groups
      accurately predicted sensitivity to a dual PI3K and mTOR inhibitor in two
      independent sets of primary AML cells isolated from patients. Thus, our study
      demonstrates KSEA as an untargeted method for the systematic profiling of kinase
      pathway activities and for increasing our understanding of diseases caused by the
      dysregulation of signaling pathways.

PMID- 23532335
TI  - Dysregulated RasGRP1 responds to cytokine receptor input in T cell
      leukemogenesis.
AB  - Enhanced signaling by the small guanosine triphosphatase Ras is common in T cell
      acute lymphoblastic leukemia/lymphoma (T-ALL), but the underlying mechanisms are
      unclear. We identified the guanine nucleotide exchange factor RasGRP1 (Rasgrp1 in
      mice) as a Ras activator that contributes to leukemogenesis. We found increased
      RasGRP1 expression in many pediatric T-ALL patients, which is not observed in
      rare early T cell precursor T-ALL patients with KRAS and NRAS mutations, such as
      K-Ras(G12D). Leukemia screens in wild-type mice, but not in mice expressing the
      mutant K-Ras(G12D) that encodes a constitutively active Ras, yielded frequent
      retroviral insertions that led to increased Rasgrp1 expression. Rasgrp1 and
      oncogenic K-Ras(G12D) promoted T-ALL through distinct mechanisms. In K-Ras(G12D)
      T-ALLs, enhanced Ras activation had to be uncoupled from cell cycle arrest to
      promote cell proliferation. In mouse T-ALL cells with increased Rasgrp1
      expression, we found that Rasgrp1 contributed to a previously uncharacterized
      cytokine receptor-activated Ras pathway that stimulated the proliferation of T
      ALL cells in vivo, which was accompanied by dynamic patterns of activation of
      effector kinases downstream of Ras in individual T-ALLs. Reduction of Rasgrp1
      abundance reduced cytokine-stimulated Ras signaling and decreased the
      proliferation of T-ALL in vivo. The position of RasGRP1 downstream of cytokine
      receptors as well as the different clinical outcomes that we observed as a
      function of RasGRP1 abundance make RasGRP1 an attractive future stratification
      marker for T-ALL.

PMID- 23532334
TI  - PUMA and BIM are required for oncogene inactivation-induced apoptosis.
AB  - The clinical efficacy of tyrosine kinase inhibitors supports the dependence of
      distinct subsets of cancers on specific driver mutations for survival, a
      phenomenon called "oncogene addiction." We demonstrate that PUMA and BIM are the
      key apoptotic effectors of tyrosine kinase inhibitors in breast cancers with
      amplification of the gene encoding human epidermal growth factor receptor 2
      (HER2) and lung cancers with epidermal growth factor receptor (EGFR) mutants. The
      BH3 domain containing proteins BIM and PUMA can directly activate the
      proapoptotic proteins BAX and BAK to permeabilize mitochondria, leading to
      caspase activation and apoptosis. We delineated the signal transduction pathways
      leading to the induction of BIM and PUMA by tyrosine kinase inhibitors.
      Inhibition of the mitogen-activated or extracellular signal-regulated protein
      kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway caused
      increased abundance of BIM, whereas antagonizing the phosphoinositide 3-kinase
      (PI3K)-AKT pathway triggered nuclear translocation of the FOXO transcription
      factors, which directly activated the PUMA promoter. In a mouse breast tumor
      model, the abundance of PUMA and BIM was increased after inactivation of HER2.
      Moreover, deficiency of Bim or Puma impaired caspase activation and reduced tumor
      regression caused by inactivation of HER2. Similarly, deficiency of Puma impeded
      the regression of EGFR(L858R)-driven mouse lung tumors upon inactivation of the
      EGFR-activating mutant. Overall, our study identified PUMA and BIM as the
      sentinels that interconnect kinase signaling networks and the mitochondrion
      dependent apoptotic program, which offers therapeutic insights for designing
      novel cell death mechanism-based anticancer strategies.

PMID- 23532337
TI  - Two-legged hopping in autism spectrum disorders.
AB  - Sensory processing deficits are common within autism spectrum disorders (ASD).
      Deficits have a heterogeneous dispersion across the spectrum and multimodal
      processing tasks are thought to magnify integration difficulties. Two-legged
      hopping in place in sync with an auditory cue (2.3, 3.0 Hz) was studied in a
      group of six individuals with expressive language impaired ASD (ELI-ASD) and an
      age-matched control group. Vertical ground reaction force data were collected and
      discrete Fourier transforms were utilized to determine dominant hopping cadence.
      Effective leg stiffness was computed through a mass-spring model representation.
      The ELI-ASD group were unsuccessful in matching their hopping cadence (2.21 +/-
      0.30 hops.s(-1), 2.35 +/- 0.41 hops.s(-1)) to either auditory cue with greater
      deviations at the 3.0 Hz cue. In contrast, the control group was able to match
      hopping cadence (2.35 +/- 0.06 hops.s(-1), 3.02 +/- 0.10 hops.s(-1)) to either
      cue via an adjustment of effective leg stiffness. The ELI-ASD group demonstrated
      a varied response with an interquartile range (IQR) in excess of 0.5 hops.s(-1)
      as compared to the control group with an IQR < 0.03 hops.s(-1). Several
      sensorimotor mechanisms could explain the inability of participants with ELI-ASD
      to modulate motor output to match an external auditory cue. These results suggest
      that a multimodal gross motor task can (1) discriminate performance among a group
      of individuals with severe autism, and (2) could be a useful quantitative tool
      for evaluating motor performance in individuals with ASD individuals.

PMID- 23532338
TI  - Nanosecond pulsed electric field thresholds for nanopore formation in neural
      cells.
AB  - The persistent influx of ions through nanopores created upon cellular exposure to
      nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal
      function. One ion, calcium (Ca(2+)), is important to action potential firing and
      regulates many ion channels. However, uncontrolled hyper-excitability of neurons
      leads to Ca(2+) overload and neurodegeneration. Thus, to prevent unintended
      consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure
      parameters is required. We determined the relationship between nsPEF exposure
      parameters (pulse width and amplitude) and nanopore formation in two cell types:
      rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We
      identified thresholds for nanoporation using Annexin V and FM1-43, to detect
      changes in membrane asymmetry, and through Ca(2+) influx using Calcium Green. The
      ED50 for a single 600 ns pulse, necessary to cause uptake of extracellular
      Ca(2+), was 1.76  kV/cm for NG108 and 0.84  kV/cm for PHN. At 16.2  kV/cm, the
      ED50 for pulse width was 95 ns for both cell lines. Cadmium, a nonspecific Ca(2+)
      channel blocker, failed to prevent Ca(2+) uptake suggesting that observed influx
      is likely due to nanoporation. These data demonstrate that moderate amplitude
      single nsPEF exposures result in rapid Ca(2+) influx that may be capable of
      controllably modulating neurological function.

PMID- 23532339
TI  - Total knee arthroplasty in extra articular deformities: A series of 36 knees.
AB  - BACKGROUND: The presence of extra articular deformities either in the femur or
      the tibia with arthritis of the knee makes total knee arthroplasty (TKA)
      technically demanding. The purpose of this study is to report outcomes with Total
      Knee Arthroplasty in patients with arthritis of the knee associated with extra
      articular deformity by intraarticular resection and soft tissue balancing.
      MATERIALS AND METHODS: Thirty six knees (32 patients) who had arthritis of the
      knee associated with extra articular deformity, underwent total knee arthroplasty
      between 1999 and 2006 were included in this retrospective analysis. All patients
      had intraarticular resection with soft tissue balancing to correct the deformity.
      Full length weight bearing anteroposterior X-rays, Knee society scores, and Knee
      range of motion was recorded pre- and postoperatively. RESULTS: The mean period
      of followup was 85 months (range 42-120 months). The deformities amenable to
      correction by intraarticular resection in our series were Femur- Coronal plane 11
      degrees -18 degrees  (mean 16.2 degrees ) Saggital plane 0 degrees -15 degrees 
      (mean 10.1 degrees ) Tibia - Coronal plane 12 degrees -24 degrees  (mean 21
      degrees ). There was an improvement in the range of motion from mean of 54
      degrees  preoperatively to 114 degrees  postoperatively (P value < 0.05). The
      Knee Society- Knee Score improved from 37 points to 85 points postoperatively (P
      value < 0.05). The functional score improved from a mean value of 19 to a mean of
      69.5 at followup (P < 0.01). The preoperative hip knee ankle angle in the coronal
      plane improved from a mean of 14 degrees  +/- 2 degrees  varus (26 degrees  varus
      to 4 degrees  valgus) to a mean of 2 degrees  +/- 0.6 degrees  varus (6 degrees 
      varus to 2 degrees  valgus). CONCLUSION: With a good preoperative planning and
      templating, intraarticular bone resection and good soft tissue balancing both in
      flexion and extension, correction would be possible in majority of extraarticular
      deformities.

PMID- 23532340
TI  - Learning that classifiers count: Mandarin-speaking children's acquisition of
      sortal and mensural classifiers.
AB  - Two experiments explored two-to five-year-old Mandarin-speaking children's
      acquisition of classifiers, mandatory morphemes for expressing quantities in many
      Asian languages. Classifiers are similar to measure words in English (e.g., a
      piece of apple; a cup of apples), with the main difference being that classifiers
      are also required when counting sortals (e.g., yi ge pinguo or "one unit apple"
      in Mandarin means "one apple"). The current study extended prior studies (e.g.,
      Chien et al., J East Asian Linguist 12:91-120, 2003) to examine Mandarin-speaking
      children's understanding of classifiers as indicating units of quantification.
      Children were also tested on their knowledge of numerals to assess the
      relationship between children's acquisition of numerals and classifiers. The
      findings suggest that children first notice that sortal classifiers specify
      properties such as shape. Only after learning some numerals do they begin to work
      out how classifiers indicate units of quantification. By age four, children
      scored above chance on most classifiers tested.

PMID- 23532341
TI  - Using the EORTC-QLQ-C30 in clinical practice for patient management: identifying
      scores requiring a clinician's attention.
AB  - PURPOSE: Patient-reported outcomes (PROs) are used increasingly for individual
      patient management. Identifying which PRO scores require a clinician's attention
      is an ongoing challenge. Previous research used a needs assessment to identify
      EORTC-QLQ-C30 cutoff scores representing unmet needs. This analysis attempted to
      replicate the previous findings in a new and larger sample. METHODS: This
      analysis used data from 408 Japanese ambulatory breast cancer patients who
      completed the QLQ-C30 and Supportive Care Needs Survey-Short Form-34 (SCNS-SF34).
      Applying the methods used previously, SCNS-SF34 item/domain scores were
      dichotomized as no versus some unmet need. We calculated area under the receiver
      operating characteristic curve (AUC) to evaluate QLQ-C30 scores' ability to
      discriminate between patients with no versus some unmet need based on SCNS-SF34
      items/domains. For QLQ-C30 domains with AUC >= 0.70, we calculated the
      sensitivity, specificity, and predictive value of various cutoffs for identifying
      unmet needs. We hypothesized that compared to our original analysis, (1) the same
      six QLQ-C30 domains would have AUC >= 0.70, (2) the same SCNS-SF34 items would be
      best discriminated by QLQ-C30 scores, and (3) the sensitivity and specificity of
      our original cutoff scores would be supported. RESULTS: The findings from our
      original analysis were supported. The same six domains with AUC >= 0.70 in the
      original analysis had AUC >= 0.70 in this new sample, and the same SCNS-SF34 item
      was best discriminated by QLQ-C30 scores. Cutoff scores were identified with
      sensitivity >=0.84 and specificity >=0.54. CONCLUSION: Given these findings'
      concordance with our previous analysis, these QLQ-C30 cutoffs could be
      implemented in clinical practice and their usefulness evaluated.

PMID- 23532342
TI  - Oligomerisation status and evolutionary conservation of interfaces of protein
      structural domain superfamilies.
AB  - Protein-protein interactions are important in carrying out many biological
      processes and functions. These interactions may be either permanent or of
      temporary nature. Several studies have employed tools like solvent accessibility
      and graph theory to identify these interactions, but still more studies need to
      be performed to quantify and validate them. Although we now have many databases
      available with predicted and experimental results on protein-protein
      interactions, we still do not have many databases which focus on providing
      structural details of the interacting complexes, their oligomerisation state and
      homologues. In this work, protein-protein interactions have been thoroughly
      investigated within the structural regime and quantified for their strength using
      calculated pseudoenergies. The PPCheck server, an in-house webserver, has been
      used for calculating the pseudoenergies like van der Waals, hydrogen bonds and
      electrostatic energy based on distances between atoms of amino acids from two
      interacting proteins. PPCheck can be visited at . Based on statistical data, as
      obtained by studying established protein-protein interacting complexes from
      earlier studies, we came to a conclusion that an average protein-protein
      interface consisted of about 51 to 150 amino acid residues and the generalized
      energy per residue ranged from -2 kJ mol(-1) to -6 kJ mol(-1). We found that some
      of the proteins have an exceptionally higher number of amino acids at the
      interface and it was purely because of their elaborate interface or extended
      topology i.e. some of their secondary structure regions or loops were either
      inter-mixing or running parallel to one another or they were taking part in
      domain swapping. Residue networks were prepared for all the amino acids of the
      interacting proteins involved in different types of interactions (like van der
      Waals, hydrogen-bonding, electrostatic or intramolecular interactions) and were
      analysed between the query domain-interacting partner pair and its remote
      homologue-interacting partner pair. We found that, in exceptional cases,
      homologous proteins belonging to the same superfamily, but with remote sequence
      similarity, can share similar interfaces.

PMID- 23532343
TI  - Endovascular treatment of post-pharyngitis internal carotid artery pseudoaneurysm
      with a covered stent in a child: a case report.
AB  - CASE REPORT: We report a case of 4-year-old boy patient, who developed after a
      streptococcal pharyngitis a painful, pulsatile, and growing right-sided mass in
      the neck. Imaging studies revealed an extracranial right internal carotid artery
      pseudoaneurysm. The patient was successfully treated with stent-graft deployment.
      After 18 months of follow-up, the pseudoaneurysm is excluded from the
      circulation, the carotid artery is patent, and the patient is free from any
      neurological deficit. DISCUSSION: Covered stents might be considered as a valid
      therapeutic option to treat carotid artery pseudoaneurysms.

PMID- 23532344
TI  - Recurrent multiple spinal paragangliomas as a manifestation of a metastatic
      composite paraganglioma-ganglioneuroblastoma.

PMID- 23532345
TI  - Emotional health and quality of life after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Emotional disorders and decrease in health-related quality of life
      (HRQoL) are well-documented sequelae of aneurysmal subarachnoid hemorrhage (SAH).
      The aim of this study was to analyze the impact of emotional disorders on HRQoL
      in survivors of SAH. METHODS: This was a retrospective study enrolling 114 SAH
      survivors at 1-10 years (mean 4,5 years) after the disease. Emotional State
      Questionnaire (EST-Q) was used to measure emotional health and the Short Form
      Health Survey (SF-36) was used to assess HRQoL of the patients. RESULTS: Most of
      the patients reported good recovery, but EST-Q results revealed high prevalence
      of emotional disorders after SAH. Almost half of the patients had higher than cut
      off values indicating fatigue (47 %) and insomnia (46 %). About one third of SAH
      patients had higher than cut-off scores demonstrating depression (30 %) and
      anxiety (31 %). The patients scored significantly lower in all scales of SF-36 as
      compared to age-matched general population. All EST-Q subscale results were
      significantly and negatively correlated with SF-36 scores. Fatigue was
      independently related to all SF-36 subscales and depression to most of the mental
      health component scores. Emotional symptoms alone were demonstrated to explain 23
      47 % of the SF-36 subscale values, and more than half of the variance of mental
      health component score values were found to be explained by emotional disorders
      (53 %). CONCLUSIONS: Emotional disorders are frequent after SAH and significantly
      associated with impairment of HRQOL. Proper and timely screening tests are
      important to reveal development of emotional problems and improve QoL for the SAH
      patients.

PMID- 23532346
TI  - Observation of the neurohypophysis, pituitary stalk, and adenohypophysis during
      endoscopic pituitary surgery: demonstrative findings as clues to pituitary
      conserving surgery.
AB  - BACKGROUND: High-definition imaging in endoscopic transsphenoidal pituitary
      surgery accounts for significantly better identification of anatomic structures.
      This report presents the clinical images of the adenohypophysis and
      neurohypophysis under high-definition endoscopic observation, and provides some
      clues for pituitary-sparing surgery. METHODS: Ten demonstrative cases of
      pituitary lesions, including three cases of gonadotropin-producing pituitary
      adenoma, two cases of somatotropin-secreting pituitary adenoma, and five cases of
      Rathke's cleft cysts, were entered in this study. From these cases, we extracted
      helpful intraoperative findings that affected the surgeon's decision about
      surgical procedures and led to favorable results. RESULTS: The extracted findings
      contain the following lessons: (1) to find a boundary plane that separate a
      lesion from the pituitary; (2) to mark the difference of color between the
      adenohypophysis and the neurohypophysis; (3) to identify the location of the
      pituitary stalk connecting to the neurohypophysis; (4) to observe the color
      change of the pituitary induced by decompression; (5) to know pathological
      findings of the pituitary surface; (6) to distinguish the parenchyma of the
      neurohypophysis from pathological tissues; and (7) to recognize the intrasellar
      findings at the completion of removal. Recognition of these findings led to an
      excellent result in each case. CONCLUSIONS: Despite being shown in a limited
      number of cases, on the basis of HD endoscopic images, accurate identification of
      the neurohypophysis and the pituitary stalk as well as adenohypophysis during
      surgery contributes to pituitary-conserving operations.

PMID- 23532347
TI  - Intervention for infants at risk of developing autism: a case series.
AB  - Theory and evidence suggest the potential value of prodromal intervention for
      infants at risk of developing autism. We report an initial case series (n = 8) of
      a parent-mediated, video-aided and interaction-focused intervention with infant
      siblings of autistic probands, beginning at 8-10 months of age. We outline the
      theory and evidence base behind this model and present data on feasibility,
      acceptability and measures ranging from parent-infant social interaction, to
      infant atypical behaviors, attention and cognition. The intervention proves to be
      both feasible and acceptable to families. Measurement across domains was
      successful and on larger samples promise to be an effective test of whether such
      an intervention in infancy will modify emergent atypical developmental
      trajectories in infants at risk for autism. 

PMID- 23532348
TI  - Co-segregation of social cognition, executive function and local processing style
      in children with ASD, their siblings and normal controls.
AB  - Cognitive research proposes that social cognition (SC), executive functions (EF)
      and local processing style (weak CC) may be fruitful areas for research into the
      familial-genetic underpinnings of Autism Spectrum Disorders (ASD). The
      performance of 140 children with ASD, 172 siblings and 127 controls on tasks
      measuring SC (face recognition, affective prosody, and facial emotion
      recognition), EF (inhibition, cognitive flexibility, and verbal working memory)
      and local processing style was assessed. Compelling evidence was found for the
      interrelatedness of SC and EF, but not local processing style, within individuals
      and within families, suggesting that these domains tend to co-segregate in ASD.
      Using the underlying shared variance of these constructs in genetic research may
      increase the power for detecting susceptibility genes for ASD. 

PMID- 23532349
TI  - Chronic diarrhea in travelers.
AB  - As a rule, travelers' diarrhea is a self-limited bacterial infection that affects
      approximately 40 % of travelers to developing countries. Health-care
      professionals who see returning travelers have noted that some travelers
      afflicted with diarrhea do not recover completely but, instead, develop chronic
      diarrhea or a persistent change in gastrointestinal function. Concurrent with
      this observation has been the recognition that in many patients with long
      standing irritable bowel syndrome, an episode of traveler's diarrhea or
      gastroenteritis preceded the onset of symptoms. Before a diagnosis of
      postinfectious irritable bowel syndrome is considered, other diagnostic
      considerations must be excluded. This review will examine an approach to the
      patient with chronic diarrhea posttravel.

PMID- 23532350
TI  - An unusual copper(I) halide-based metal-organic framework with a cationic
      framework exhibiting the release/adsorption of iodine, ion-exchange and
      luminescent properties.
AB  - A copper(I) halide-based compound with a formula of [Cu4I3(DABCO)2]I3 (DABCO =
      N,N'-dimethyl-1,4-diazabicyclo[2.2.2]octane) has been prepared by solvothermal
      reactions. This compound has been characterized by single-crystal X-ray
      diffraction, elemental analysis, IR, TG, XPS and powder X-ray diffractions.
      Structure analyses reveal that this compound is constructed by unprecedented
      cationic cluster [Cu8I6](2+) and organic ligand DABCO and the channels of this
      compound are occupied by I2 and I(-). The guest I2 and I(-) can move freely in
      and out of the host-framework. UV/vis spectra confirm that the I2 molecules in
      the channels can release into some organic solvents and IR spectra confirm the I(
      ) was exchanged by SCN(-). In addition, the luminescent properties of this
      compound in the solid state have also been investigated.

PMID- 23532351
TI  - Human exposure to particulate matter potentially contaminated with sin nombre
      virus.
AB  - The most common mechanism for human exposure to hantaviruses throughout North
      America is inhalation of virally contaminated particulates. However, risk factors
      associated with exposure to particulates potentially contaminated with
      hantaviruses are generally not well understood. In North America, Sin Nombre
      virus (SNV) is the most common hantavirus that infects humans, causing hantavirus
      pulmonary syndrome, which has a significant mortality rate (approximately 35%).
      We investigated human exposure to particulate matter and evaluated the effects of
      season, location (sylvan and peridomestic environment), and activity (walking and
      sweeping) on generation of particulates at the breathing zone (1.5 m above the
      ground). We found greater volumes of small inhalable particulates during the
      spring and summer compared to the fall and winter seasons and greater volumes of
      small inhalable particulates produced in peridomestic, compared to sylvan,
      environments. Also, greater volumes of particulates were generated at the
      breathing zone while walking compared to sweeping. Results suggest that more
      aerosolized particles were generated during the spring and summer months. Our
      findings suggest that simply moving around in buildings is a significant source
      of human exposure to particulates, potentially contaminated with SNV, during
      spring and summer seasons. These findings could be advanced by investigation of
      what particle sizes SNV is most likely to attach to, and where in the respiratory
      tract humans become infected.

PMID- 23532352
TI  - Dermoscopic characteristics of acquired melanocytic naevus in childhood affecting
      the acral region.

PMID- 23532353
TI  - Does video-assisted thoracic surgery provide a safe alternative to conventional
      techniques in patients with limited pulmonary function who are otherwise suitable
      for lung resection?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was: does video-assisted thoracic surgery
      provide a safe alternative to conventional techniques in patients with limited
      pulmonary function who are otherwise suitable for lung resection? Altogether,
      more than 280 papers were found using the reported search, of which 7 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. One of the largest studies reviewed was a
      retrospective review of the Society of Thoracic Surgeons database. The authors
      compared 4531 patients who underwent lobectomy by video-assisted thoracic surgery
      (VATS) with 8431 patients who had thoracotomy. In patients with a predicted
      postoperative forced expiratory volume in 1 s (ppoFEV1%) of <60, it was
      demonstrated that thoracotomy patients have markedly increased pulmonary
      complications when compared with VATS patients (P = 0.023). Another study
      compared perioperative outcomes in patients with a ppoFEV1% of <40% who underwent
      thoracoscopic resection with similar patients who underwent open resection.
      Patients undergoing thoracoscopic resection as opposed to open thoracotomy had a
      lower incidence of pneumonia (4.3 vs 21.7%, P < 0.05), a shorter intensive care
      stay (2 vs 4 days, P = 0.05) and a shorter hospital stay (7 vs 10 days, P =
      0.058). A similar study compared recurrence and survival in patients with a
      ppoFEV1% of <40% who underwent resection by VATS or anatomical segmentectomy
      (study group) with open resection (control group). Relative to the control group,
      patients in the study group had a shorter length of hospital stay (8 vs 12 days,
      P = 0.054) and an improved 5-year survival (42 vs 18%, P = 0.02). Analysis
      suggested that VATS lobectomy was the principal driver of survival benefit in the
      study group. We conclude that patients with limited pulmonary function have
      better outcomes when surgery is performed via VATS compared with traditional open
      techniques. The literature also suggests that patients in whom pulmonary function
      is poor have similar perioperative outcomes to those with normal function when a
      VATS approach to resection is adopted.

PMID- 23532354
TI  - A new intermediate in the Prins reaction.
AB  - Two Prins reactions were investigated by the use of DFT calculations. A model
      composed of R-CH=CH2 + H3O(+)(H2O)13 + (H2C=O)2, R = Me and Ph, was adopted to
      trace reaction paths. For both alkenes, the concerted path forming 1,3-diols was
      obtained as the rate determining step (TS1). TS stands for a transition state.
      From the 1,3-diol, a bimolecular elimination (TS2) leads to the allylic alcohol
      as the first channel. In the second channel, the 1,3-diol was converted via TS3
      into an unprecedented hemiacetal intermediate, HO-CH2-O-CH(R)-CH2-CH2-OH. This
      intermediate undergoes ring closure (TS4), affording the 1,3-dioxane product. The
      intermediate is of almost the same stability as the product, and two species were
      suggested to be in a state of equilibrium. While the geometry of TS1 appears to
      be forwarded to that of a carbocation intermediate, the cation disappeared
      through the enlargement of the water cluster. Dynamical calculations of a
      classical trajectory using the atom-centered density matrix propagation molecular
      dynamics model on the four TSs were carried out, and results of IRC calculations
      were confirmed by them.

PMID- 23532355
TI  - Factors affecting hospital length of stay following anterior cervical discectomy
      and fusion.
AB  - STUDY DESIGN:  Retrospective cohort study. BACKGROUND:  Several studies focus on
      the long-term results of anterior cervical discectomy and fusion (ACDF)
      surgeries, but little information exists regarding how various patient-related,
      procedure-related, and payer-related variables may affect postoperative hospital
      length of stay (LOS). OBJECTIVE:  To determine what factors, if any, contribute
      to increased hospital LOS in patients who have had an ACDF. METHODS: 
      Retrospective cohort study of 108 consecutive patients who underwent elective
      ACDF at a Midwest academic medical center. Extensive preoperative,
      intraoperative, and postoperative data were abstracted and analyzed to identify
      prognostic factors for an increased LOS. Multivariate analysis was performed to
      analyze the effects of patient and hospital characteristics on hospital LOS.
      RESULTS:  103 patients met inclusion and exclusion criteria. The mean LOS for
      patients undergoing ACDF was 1.98 (+/-1.6) days. Only 29% of patients had one
      level fused. The mean blood loss during surgery was 87.4 +/- 99.6 mL. One subject
      lost 700 mL of blood. Complications, though rare, included uncontrolled
      postoperative pain (13%), cardiac (6%), pulmonary (4%), and urinary (3%).
      Covariates included in the final model were age, sex, cardiac complication,
      urinary complication, and pulmonary complication. Factors that contributed to
      increased LOS and their associated adjusted mean days were: >=50 years of age
      (2.5 +/- 1.2 days), female gender (2.3 +/- 1.2 days), and three particular types
      of complications. The complications that had the largest effect on increased LOS
      from least to most severe were cardiac (3.5 +/- 1.3 days), urinary (4.7 +/- 1.3
      days), and pulmonary (5.3 +/- 1.3 days). CONCLUSIONS:  The information presented
      in this study may be useful for patients, clinicians, and insurance companies,
      including precertification and case-management services. Our results can be
      instrumental in designing future prospective studies using more detailed analyses
      with more patients, more surgeons, and multiple institutions. [Table: see text].

PMID- 23532357
TI  - Cutaneous Mycobacterium intracellulare infection in an immuno-competent person.
AB  - Mycobacterium intracellulare-caused pulmonary infections have mostly been
      reported in immunocompromised hosts, while cutaneous M. intracellulare infections
      are rare. We describe here an immunocompetent patient with cutaneous lesions due
      to M. intracellulare, which was diagnosed by acid-fast staining, in vitro
      culture, histopathology, and PCR-restriction fragment length polymorphism
      analysis and gene sequencing of heat-shock protein (hsp) 65 and 16S rDNA genes.
      In vitro susceptibility testing was also carried out and the patient was
      successfully treated with clarithromycin, rifampicin, and ethambutol. 

PMID- 23532356
TI  - When and where do hip fractures occur? A population-based study.
AB  - We investigated the effects of socio-demographic and health factors on timing and
      location of hip fracture among 484 subjects. Time of fracture varied between
      community dwellers and residential care facility dwellers, and in relation to
      subjects' psychotropic drug status. Indoor hip fracture incidence increased on
      snow-covered days. INTRODUCTION: This paper aims to describe the timing and
      whereabouts of hip fracture cases in a population-based setting and to relate
      these factors with residential and health status, seasonal variation, and snow
      covered ground. METHODS: We consecutively included 484 incident hip fracture
      events (age >=50 years) admitted to a Swedish orthopedic department during a 1
      year period. Data concerning socio-demographic details, fall location, time of
      fracture, comorbidity, and medications were collected from in-patient medical
      records and through patient or caregiver interviews. RESULTS: The expected peak
      in fracture occurrence during daytime was observed among community dwellers but
      not among subjects living in residential care. Hip fracture was twice as likely
      to occur during nighttime hours among psychotropic drug users (adjusted odds
      ratio (Adj. OR), 2.20; 95% confidence interval (CI), 1.12-4.30) compared to those
      not receiving these medications. Subjects without dementia, taking psychotropic
      drugs, were also more likely to fracture during nighttime hours (Adj. OR, 2.91;
      95% CI, 1.40-6.0). We observed an increase in indoor hip fracture incidence on
      snow-covered days among community dwellers (incidence rate ratio, 1.34; 95% CI,
      1.02-1.74). We observed only a weak seasonal trend in hip fracture incidence,
      based on month, among community dwellers who fractured indoors. CONCLUSIONS:
      Special attention and possibly fall-preventive efforts should be directed not
      only toward those living in residential care facilities but also toward community
      dwelling subjects taking psychotropic drugs since these groups have a higher
      incidence of nighttime hip fracture. Further research aiming to explain the
      seasonal variation of indoor fracture incidence among community dwellers is
      warranted.

PMID- 23532358
TI  - Single-cell polymerase chain reaction-based pre-implantation genetic diagnosis
      using fragment analysis for beta-thalassemia in an Indian couple with beta-globin
      gene mutations.
AB  - Despite advances in diagnostic techniques, approximately 10,000 babies with beta
      thalassemia major are born annually in India. Pre-implantation genetic diagnosis
      (PGD), an alternative to prenatal diagnosis, helps in negative selection of
      affected embryos prior to implantation. Hereby, we report the first successful
      beta-thalassemia PGD pregnancy in an Indian carrier couple. beta-Thalassemia
      mutation analysis by Amplification-Refractory Mutation Sequence (ARMS)-polymerase
      chain reaction (PCR) in the parents, followed by PGD for beta-thalassemia
      mutation in embryos in two consequent in vitro fertilization (IVF) cycles, with
      transfer for three beta-thalassemia minor embryos, resulted in singleton
      successful pregnancy, the results of which were confirmed on prenatal diagnosis.
      With advances in assisted reproductive techniques and molecular diagnosis, PGD
      for monogenic diseases is feasible in high-risk couples. The methodology in the
      current study included two rounds of PCR using fluorescently labeled primers,
      fragment analysis using the ABI 3100 nucleotide sequencer and the GeneMapper
      software, purification, and concentration of PCR product, which enabled distinct
      clear peaks making the analysis and interpretation non-ambiguous.

PMID- 23532359
TI  - Polar body fragmentation in IVM oocytes is associated with impaired fertilization
      and embryo development.
AB  - PURPOSE: The significance of finding a fragmented first polar body in an oocyte
      prepared for ICSI is controversial with most recent publications suggesting that
      it is not prognostic for oocyte fertilization or embryo development. Our purpose
      was to look at this question in the context of oocytes not stimulated for
      conventional IVF. METHODS: Oocytes obtained for IVM and obtained from follicles
      at most 12 mm in diameter were evaluated for their polar body morphology soon
      after they entered metaphase II when they were denuded in preparation for ICSI.
      Records were evaluated retrospectively for the fertilization rate and the embryo
      growth rate (cell number) on each day of development for embryos with normal
      appearing polar bodies or fragmented polar bodies, but no other cytoplasmic
      dysmorphisms. RESULTS: Oocytes with fragmented polar bodies were significantly
      less likely to fertilize than oocytes with normal appearing polar bodies (p <
      0.0001). Embryos which developed from oocytes with fragmented polar bodies had
      significantly impaired growth compared to embryos that developed from oocytes
      with normal appearing polar bodies (p = 0.0328). CONCLUSIONS: Fragmented polar
      bodies likely reflect cytoplasmic incompetence.

PMID- 23532360
TI  - Gender differences in cholinergic and dopaminergic deficits in Parkinson disease.
AB  - As Parkinson disease (PD) may affect men and women differentially, we
      investigated gender differences in regional projection system integrity in 148 PD
      subjects (36 women, 112 men) using monoaminergic [11C]dihydrotetrabenazine and
      acetylcholinesterase [11C]PMP positron emission tomography. After controlling for
      age, disease duration, and Hoehn and Yahr score, men showed 5.9% greater caudate
      dopaminergic denervation (p = 0.0018) and 5.8% greater neocortical cholinergic
      denervation (p = 0.0097). No significant gender differences were seen in
      putaminal dopaminergic or thalamic cholinergic denervation.

PMID- 23532361
TI  - Dual-donor (Zn(i) and V(O)) mediated ferromagnetism in copper-doped ZnO micron
      scale polycrystalline films: a thermally driven defect modulation process.
AB  - The paper reports robust ferromagnetic Cu-doped ZnO micron-scale polycrystalline
      films via spin-coating using high-quality doped nanocrystals. A reliable magnetic
      response is observed in the 900  degrees C vacuum annealed film without any
      ferromagnetic contribution from other sources. Post-annealing treatment in terms
      of atmosphere and temperature can control the proportion of oxygen vacancies
      (V(O)) and zinc interstitials (Zn(i)) defects and further help to precisely
      regulate defect-related ferromagnetic behavior. Complex charge transfer processes
      derived from dual-donor (Zn(i) and V(O)) to Cu acceptor are revealed by
      photoluminescence (PL) and electron paramagnetic resonance (EPR) spectra. Based
      on the above, specific charge transfer (CT)-type Stoner splitting and indirect
      double-exchange mechanisms are proposed to understand the ferromagnetic origin.
      The improvable FM performance and annealing-specific modulation further indicate
      that a thermal driven process can delicately tailor the magnetic property of the
      transition metal ion-doped ZnO system.

PMID- 23532362
TI  - Variable extent of parallelism in respiratory, circulatory, and neurological
      traits across lake whitefish species pairs.
AB  - Parallel adaptive radiation events provide a powerful framework for
      investigations of ecology's contribution to phenotypic diversification.
      Ecologically driven divergence has been invoked to explain the repeated evolution
      of sympatric dwarf and normal lake whitefish (Coregonus clupeaformis) species in
      multiple lakes in eastern North America. Nevertheless, links between most
      putatively adaptive traits and ecological variation remain poorly defined within
      and among whitefish species pairs. Here, we examine four species pairs for
      variation in gill, heart, and brain size; three traits predicted to show strong
      phenotypic responses to ecological divergence. In each of the species pairs,
      normals exhibited larger body size standardized gills compared to dwarfs - a
      pattern that is suggestive of a common ecological driver of gill size divergence.
      Within lakes, the seasonal hypoxia experienced in the benthic environment is a
      likely factor leading to the requirement for larger gills in normals.
      Interestingly, the morphological pathways used to achieve larger gills varied
      between species pairs from Quebec and Maine, which may imply subtle non
      parallelism in gill size divergence related to differences in genetic background.
      There was also a non-significant trend toward larger hearts in dwarfs, the more
      active species of the two, whereas brain size varied exclusively among the lake
      populations. Taken together, our results suggest that the diversification of
      whitefish has been driven by parallel and non-parallel ecological conditions
      across lakes. Furthermore, the phenotypic response to ecological variation may
      depend on genetic background of each population.

PMID- 23532363
TI  - Elevated lipoprotein(a) levels and homozygous human platelet antigen 1b (HPA-1b)
      genotype are risk factors for intrauterine growth restriction (IUGR).
AB  - The risk of premature manifestation of cardiovascular disease is higher in women
      after a maternal placental syndrome, especially with a history of fetal IUGR. Aim
      of the study was to assess hereditary risk factors for arterial thrombosis as
      risk factors for IUGR. 183 women with fetal IUGR birth weight below the 10th
      percentile for gestational age and 300 control women were evaluated using a case
      control design. In 121 of the 183 women, the newborns' birth weight was below the
      5th percentile for gestational age. A risk association could be shown for
      homozygous human platelet antigen 1b genotype (OR 3.2, P = 0.038) in women with a
      history for a newborn's birth weight below the 5th percentile. Elevated levels of
      lipoprotein(a) (>0.7 g/l [95 % percentile], OR 2.9, P = 0.048) also represent a
      risk association in the same group of subjects. So did elevated levels of
      lipoprotein(a) (>0.7 g/l [95 % percentile], OR 3.4, P = 0.015) in women with a
      history for a newborn's birth weight below the 10th percentile. Risk factors of
      arterial thrombosis such as platelet receptor genotypes associated with platelet
      thrombogenicity and elevated levels of lipoprotein(a) might be of importance in
      the pathogenesis of IUGR. 

PMID- 23532364
TI  - Practical issues, limitations, and periprocedural management of the NOAC's.
AB  - The recent introduction of new oral anticoagulants or novel target specific oral
      anticoagulants (TSOA's) is likely to have a major impact in the years ahead. Many
      large clinical trials have been published in the past few years showing these
      agents are generally safe and effective in several clinical settings including
      acute venous thromboembolic disease, prophylaxis in the postoperative setting,
      prevention of thromboembolism in patients with atrial fibrillation, and in the
      management of acute coronary syndromes. Reported rates of overall and
      intracranial bleeding are lower compared to oral vitamin K antagonists. Other
      major advantages of oral direct thrombin inhibitors (dabigatran) and Xa
      inhibitors (rivaroxaban and apixaban) include rapid onset and offset of action
      and predictable pharmacodynamics with relatively wide therapeutic window allowing
      for unmonitored drug use. The relatively short half-life, rapid onset of action,
      and predictable pharmacokinetics should simplify periprocedural use of these
      agents. In this review we focus on some practical issues related to TSOA's
      including some limitations, potential complications, considerations to be made
      for certain patient populations, periprocedural management and issues pertaining
      to transition to and from these novel agents. 

PMID- 23532365
TI  - Role of the new oral anticoagulants in treatment of venous throboembolism.

PMID- 23532366
TI  - A biologically active surface enzyme assembly that attenuates thrombus formation.
AB  - Activation of hemostatic pathways by blood-contacting materials remains a major
      hurdle in the development of clinically durable artificial organs and implantable
      devices. We postulate that surface-induced thrombosis may be attenuated by the
      reconstitution onto blood contacting surfaces of bioactive enzymes that regulate
      the production of thrombin, a central mediator of both clotting and platelet
      activation cascades. Thrombomodulin (TM), a transmembrane protein expressed by
      endothelial cells, is an established negative regulator of thrombin generation in
      the circulatory system. Traditional techniques to covalently immobilize enzymes
      on solid supports may modify residues contained within or near the catalytic
      site, thus reducing the bioactivity of surface enzyme assemblies. In this report,
      we present a molecular engineering and bioorthogonal chemistry approach to site
      specifically immobilize a biologically active recombinant human TM fragment onto
      the luminal surface of small diameter prosthetic vascular grafts. Bioactivity and
      biostability of TM modified grafts is confirmed in vitro and the capacity of
      modified grafts to reduce platelet activation is demonstrated using a non-human
      primate model. These studies indicate that molecularly engineered interfaces that
      display TM actively limit surface-induced thrombus formation.

PMID- 23532367
TI  - CMCpy: Genetic Code-Message Coevolution Models in Python.
AB  - Code-message coevolution (CMC) models represent coevolution of a genetic code and
      a population of protein-coding genes ("messages"). Formally, CMC models are sets
      of quasispecies coupled together for fitness through a shared genetic code.
      Although CMC models display plausible explanations for the origin of multiple
      genetic code traits by natural selection, useful modern implementations of CMC
      models are not currently available. To meet this need we present CMCpy, an object
      oriented Python API and command-line executable front-end that can reproduce all
      published results of CMC models. CMCpy implements multiple solvers for leading
      eigenpairs of quasispecies models. We also present novel analytical results that
      extend and generalize applications of perturbation theory to quasispecies models
      and pioneer the application of a homotopy method for quasispecies with non-unique
      maximally fit genotypes. Our results therefore facilitate the computational and
      analytical study of a variety of evolutionary systems. CMCpy is free open-source
      software available from http://pypi.python.org/pypi/CMCpy/.

PMID- 23532369
TI  - IDH1 and IDH2 mutations in gliomas.
AB  - Mutations in isocitrate dehydrogenase (IDH) 1 and 2, originally discovered in
      2008, occur in the vast majority of low-grade gliomas and secondary high-grade
      gliomas. These mutations, which occur early in gliomagenesis, change the function
      of the enzymes, causing them to produce 2-hydroxyglutarate, a possible
      oncometabolite, and to not produce NADPH. IDH mutations are oncogenic, although
      whether the mechanism is through alterations in hydroxylases, redox potential,
      cellular metabolism, or gene expression is not clear. The mutations also drive
      increased methylation in gliomas. Gliomas with mutated IDH1 and IDH2 have
      improved prognosis compared with gliomas with wild-type IDH. Mutated IDH can now
      be detected by immunohistochemistry and magnetic resonance spectroscopy. No drugs
      currently target mutated IDH, although this remains an area of active research.

PMID- 23532368
TI  - Tumor-infiltrating immune cells: triggers for tumor capsule disruption and tumor
      progression?
AB  - BACKGROUND: Our previous studies of human breast and prostate cancer have shown
      that aberrant immune cell infiltration is associated with focal tumor capsule
      disruption and tumor cell budding that facilitate invasion and metastasis. Our
      current study attempted to determine whether aberrant immune cell infiltration
      would have similar impact on colorectal cancer (CRC). MATERIALS AND METHODS:
      Tissue sections from 100 patients with primary CRC were assessed for the
      frequencies of focal basement membrane (BM) disruption, muscularis mucosa (MM)
      fragmentation, and tumor cell dissemination in epithelial structures adjacent and
      distal to infiltrating lymphoid aggregates using a panel of biomarkers and
      quantitative digital imaging. RESULTS: Our study revealed: (1) epithelial
      structures adjacent to lymphoid follicles or aggregates had a significantly
      higher (p<0.001) frequency of focally disrupted BM, dissociated epithelial cells
      in the stroma, disseminated epithelial cells within lymphatic ducts or blood
      vessels, and fragmented MM than their distal counterparts, (2) a majority of
      dissociated epithelial cells within the stroma or vascular structures were
      immediately subjacent to or physically associated with infiltrating immune cells,
      (3) the junctions of pre-invasive and invasive lesions were almost exclusively
      located at sites adjacent to lymphoid follicles or aggregates, (4) infiltrating
      immune cells were preferentially associated with epithelial capsules that show
      distinct degenerative alterations, and (5) infiltrating immune cells appeared to
      facilitate tumor stem cell proliferation, budding, and dissemination.
      CONCLUSIONS: Aberrant immune cell infiltration may have the same destructive
      impact on the capsule of all epithelium-derived tumors. This, in turn, may
      selectively favor the proliferation of tumor stem or progenitor cells overlying
      these focal disruptions. These proliferating epithelial tumor cells subsequently
      disseminate from the focal disruption leading to tumor invasion and metastasis.

PMID- 23532370
TI  - Issues in characterizing resting energy expenditure in obesity and after weight
      loss.
AB  - Limitations of current methods: Normalization of resting energy expenditure (REE)
      for body composition using the 2-compartment model fat mass (FM), and fat-free
      mass (FFM) has inherent limitations for the interpretation of REE and may lead to
      erroneous conclusions when comparing people with a wide range of adiposity as
      well as before and after substantial weight loss. EXPERIMENTAL OBJECTIVES: We
      compared different methods of REE normalization: (1) for FFM and FM (2) by the
      inclusion of %FM as a measure of adiposity and (3) based on organ and tissue
      masses. RESULTS were compared between healthy subjects with different degrees of
      adiposity as well as within subject before and after weight loss. RESULTS:
      Normalizing REE from an "REE vs. FFM and FM equation" that (1) was derived in
      obese participants and applied to lean people or (2) was derived before weight
      loss and applied after weight loss leads to the erroneous conclusion of a lower
      metabolic rate (i) in lean persons and (ii) after weight loss. This is revealed
      by the normalization of REE for organ and tissue masses that was not
      significantly different between lean and obese or between baseline and after
      weight loss. There is evidence for an increasing specific metabolic rate of FFM
      with increasing %FM that could be explained by a higher contribution of liver,
      kidney and heart mass to FFM in obesity. Using "REE vs. FFM and FM equations"
      specific for different levels of adiposity (%FM) eliminated differences in REE
      before and after weight loss in women. CONCLUSION: The most established method
      for normalization of REE based on FFM and FM may lead to spurious conclusions
      about metabolic rate in obesity and the phenomenon of weight loss-associated
      adaptive thermogenesis. Using %FM-specific REE prediction from FFM and FM in kg
      may improve the normalization of REE when subjects with wide differences in %FM
      are investigated.

PMID- 23532371
TI  - No difference in mortality between cemented and uncemented hemiprosthesis for
      elderly patients with cervical hip fracture. A prospective randomized study on
      334 patients over 75 years.
AB  - INTRODUCTION: Laboratory and human mechanical studies indicated that chemical
      substances in bone cement had toxic and prothrombotic effects. Impaction of
      cement added a mechanical trauma to the reaming and broaching procedure and
      contributed to a substantial local and systemic thrombin generation. Case reports
      and materials have indicated bone cement as the immediate trigger of
      cardiorespiratory and vascular dysfunction, occasionally fatal, and described as
      the bone cement implantation syndrome. In spite of this knowledge, bone cement
      has gained popularity and is widely used for prosthesis fixation, possibly due to
      a lack of clinical evidence supporting the basic science indicating bone cement
      as a mortality risk factor. METHOD: This is a prospective, randomized study
      comparing cemented and non cemented hemiprosthesis on patients suffering a
      dislocated cervical hip fracture. Perioperative characteristics and 1 year
      mortality differences between the groups were estimated. PATIENTS: Hundred and
      thirty-four patients over 75 years were enrolled from two hospitals in Norway.
      Average age was 84 years, 75 % were female and 60 % had symptomatic
      comorbidities. RESULTS: We find no difference in mortality between cemented and
      uncemented hemiprosthesis up to 1 year (HR 0.77, 95 % CI 0.51-1.18, p = 0.233).
      However, statistically significant reduced operation time and blood loss were
      found in the non-cemented group. (mean difference of 13 min, 95 % CI 4-22, p =
      0.004 and 92 ml 95 % CI 3-181, p = 0.043, respectively). CONCLUSION: Installation
      of non-cemented hemiprostheses in elderly with hip fracture may have benefits
      perioperatively regarding operation time and bleeding, and do not seem to
      influence 1 year mortality relative to cemented implants.

PMID- 23532372
TI  - Healing process after rigid plate fixation of humeral shaft fractures revisited.
AB  - OBJECTIVE: The purpose of this study was to describe the radiological healing
      process after open reduction and internal fixation (ORIF) of humeral shaft
      fractures with plate. MATERIALS AND METHODS: We reviewed the data of 53
      consecutive patients who had undergone rigid plate fixation of OTA 12 A or B
      humeral shaft fracture. The mean age of the patients at the time of surgery was
      39.4 (range 16-82). Quality of reduction and healing process was analysed on
      radiographs. Clinical symptom and disabilities of the arm, shoulder and hand
      (DASH) scores were recorded at follow-up visits. RESULTS: There were 28
      compression and 25 neutralization platings. The mean gap size on the
      postoperative radiograph was 1.4 (range 0.1-6.1). 50 cases (94.3 %) healed, while
      three cases ended up with non-union. 28 (52.8 %) cases showed primary healing and
      22 cases (41.5 %) showed secondary healing with callus bridging. Among the cases
      with secondary healing, callus formation with resorption was identified in 13
      cases. The type of fracture, mode of compression and size of gap on radiographs
      after rigid plate fixation were found to be statistically significant factors for
      healing type (p = 0.026, 0.002, and <0.001, respectively). Three cases with non
      union showed no improvement in DASH scores. CONCLUSION: Both primary and
      secondary healing processes were observed after rigid plate fixation of OTA 12 A
      or B humeral shaft fractures. Our study revealed that size of gap, mode of
      compression, type of fracture could affect the type of healing, and that
      periosteal callus formation can occur after rigid plate fixation.

PMID- 23532373
TI  - Abrogation of IL-4 receptor-alpha-dependent alternatively activated macrophages
      is sufficient to confer resistance against pulmonary cryptococcosis despite an
      ongoing T(h)2 response.
AB  - In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4
      receptor alpha (IL-4Ralpha)-dependent polyfunctional T(h)2 cells induce disease
      progression associated with alternative activation of lung macrophages. To
      characterize the effector role of IL-4Ralpha-dependent alternatively activated
      macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL
      4Ralpha expression on macrophages (LysM(Cre)IL-4Ralpha(-/lox) mice) and IL
      4Ralpha(-/lox) littermates. LysM(Cre)IL-4Ralpha(-/lox) mice were significantly
      more resistant to pulmonary cryptococcosis with higher survival rates and lower
      lung burden than non-deficient heterozygous littermates. Infected LysM(Cre)IL
      4Ralpha(-/lox) mice had reduced but detectable numbers of aaMph expressing
      arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression
      of inducible nitric oxide synthase was found in LysM(Cre)IL-4Ralpha(-/lox) and IL
      4Ralpha(-/lox) control mice, but macrophages from LysM(Cre)IL-4Ralpha(-/lox) mice
      showed a higher potential to produce nitric oxide. In contrast to the differences
      in the macrophage phenotype, pulmonary T(h)2 responses were similar in infected
      LysM(Cre)IL-4Ralpha(-/lox) and IL-4Ralpha(-/lox) mice with each mouse strain
      harboring polyfunctional T(h)2 cells. Consistently, type 2 pulmonary allergic
      inflammation associated with eosinophil recruitment and epithelial mucus
      production was present in lungs of both LysM(Cre)IL-4Ralpha(-/lox) and IL
      4Ralpha(-/lox) mice. Our results demonstrate that, despite residual IL-4Ralpha
      independent alternative macrophage activation and ongoing T(h)2-dependent
      allergic inflammation, abrogation of IL-4Ralpha-dependent aaMph is sufficient to
      confer resistance in pulmonary cryptococcosis. This is even evident on a
      relatively resistant heterozygous IL-4Ralpha(+/-) background indicating a key
      contribution of macrophage IL-4Ralpha expression to susceptibility in allergic
      bronchopulmonary mycosis.

PMID- 23532374
TI  - Meta review of systematic and meta analytic reviews on movement differences,
      effect of movement based interventions, and the underlying neural mechanisms in
      autism spectrum disorder.
AB  - PURPOSES: To identify and appraise evidence from published systematic and meta
      analytic reviews on (1) movement differences of individuals with autism spectrum
      disorders (ASD); (2) the effects of movement based interventions for ASD; (3)
      hypothesized underlying neural mechanisms for the movement characteristics.
      METHODS: A meta review of published systematic and meta analytic reviews on
      movement differences, structural, and functional brain anomalies in ASD and the
      effects of movement based interventions for individuals with ASD between 1806 and
      October 2012. The methodological quality of the identified systematic and meta
      analytic reviews was independently assessed by two assessors with the assessment
      of multiple systematic reviews (AMSTAR). RESULTS: The search yielded a total of
      12 reviews that met the inclusion/exclusion criteria. The methodological quality
      of the reviews varied, but the review conclusions were similar. Although
      individuals with ASD generally perform less well than age-matched controls in
      developmental movement tasks, there are few exceptions whose movement abilities
      are intact. Most movement based interventions report their efficacies. However,
      all existing studies employ the research design that is inherently incapable of
      providing strong evidence, and they often fail to report the extent of
      psychosocial interactions within the movement interventions. The hypothesized
      neural mechanisms are still under development and speculative in nature.
      CONCLUSIONS: It is premature to designate movement disturbance as a core symptom
      of ASD. The effects of movement based interventions on the present ASD core
      symptoms need to be further validated by stronger evidence and verified
      theoretical mechanisms linking ASD with movement disorders.

PMID- 23532376
TI  - Preparation of tetrabutylammonium salt of a mono-Ru(III)-substituted alpha-Keggin
      type silicotungstate with a 4,4'-bipyridine ligand and its electrochemical
      behaviour in organic solvents.
AB  - The tetrabutylammonium (TBA) salt of a mono-ruthenium(III)-substituted alpha
      Keggin-type silicotungstate with a 4,4'-bipyridine (bipy) ligand, TBA5[alpha
      SiW11O39Ru(III)(bipy)] (1), which is soluble in various organic solvents, was
      prepared by a cation exchange reaction of Cs5[alpha-SiW11O39Ru(III)(bipy)] with
      tetrabutylammonium bromide. Compound 1 was characterised using IR, (1)H-NMR,
      elemental analysis, single crystal X-ray analysis, X-ray absorption near-edge
      structure (XANES) analysis (Ru L3-edge), electron spin resonance (ESR), cyclic
      voltammetry (CV) and UV-Vis. Single crystal X-ray analysis of 1 revealed that the
      Ru(III) unit was incorporated into the alpha-Keggin-type silicotungstate
      framework and coordinated by a bipy molecule through a Ru-N bond. CV indicated
      that the incorporated Ru(III)-bipy was reversibly oxidised to the Ru(IV)-bipy
      derivative and reduced to the Ru(II)-bipy derivative in organic solvents. The
      redox potential of Ru(IV/III)-bipy was found to be affected by organic solvents.
      Moreover, the Ru(V)-bipy derivative was observed in acetonitrile.

PMID- 23532375
TI  - ERP evidence suggests executive dysfunction in ecstasy polydrug users.
AB  - BACKGROUND: Deficits in executive functions such as access to semantic/long-term
      memory have been shown in ecstasy users in previous research. Equally, there have
      been many reports of equivocal findings in this area. The current study sought to
      further investigate behavioural and electro-physiological measures of this
      executive function in ecstasy users. METHOD: Twenty ecstasy-polydrug users, 20
      non-ecstasy-polydrug users and 20 drug-naive controls were recruited.
      Participants completed background questionnaires about their drug use, sleep
      quality, fluid intelligence and mood state. Each individual also completed a
      semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures
      were recorded. RESULTS: Analysis of Variance (ANOVA) revealed no between-group
      differences in behavioural performance on the task. Mixed ANOVA on event-related
      potential (ERP) components P2, N2 and P3 revealed significant between-group
      differences in the N2 component. Subsequent exploratory univariate ANOVAs on the
      N2 component revealed marginally significant between-group differences, generally
      showing greater negativity at occipito-parietal electrodes in ecstasy users
      compared to drug-naive controls. Despite absence of behavioural differences,
      differences in N2 magnitude are evidence of abnormal executive functioning in
      ecstasy-polydrug users.

PMID- 23532377
TI  - Computed tomographic evaluation of femoral component rotation in total knee
      arthroplasty.
AB  - BACKGROUND: Optimal femoral component rotational alignment in total knee
      arthroplasty (TKA) is crucial to establish a balanced knee reconstruction.
      Unbalanced knees can lead to instability, patellofemoral problems, persistent
      pain, stiffness, and generally poorer outcomes including early failure.
      Intraoperative techniques to achieve this optimal femoral component rotation
      include the use of the transepicondylar axis (TEA), the posterior-condylar-cut
      parallel-to-the-tibial-cut (PCCPTC) technique and the anteroposterior axis
      technique (Whiteside's line). The purpose of this study was to compare the PCCPTC
      technique to the TEA technique using computed tomography (CT) scans to assess
      femoral component rotational alignment. MATERIALS AND METHODS: This study used
      postoperative CT scans to compare the degree of femoral component rotation
      obtained with the use of PCCPTC technique and the TEA. The femoral component
      rotation of 30 TKA was measured on postoperative CT scans the angle of deviation
      between the two lines radiographic trans-epicondylar axis (rTEA) and femoral
      prosthesis posterior condylar line (FPPCL) was determined. This angle represented
      the rotation of the femoral component relative to the true rTEA. RESULTS: The
      degree of rotation measured 2.67 +/- 1.11 degrees in the PCCPTC group and 5.60 +/
      1.64 degrees in the TEA group. CONCLUSION: The use of the TEA technique for
      determining rotational alignment in TKR results in excessive external rotation of
      the femoral component compared to the PCCPTC technique.

PMID- 23532378
TI  - Use of CT-guided periradicular injection for the treatment of foraminal and
      extraforaminal disc herniations.
AB  - STUDY DESIGN:  Retrospective case series. Evidence level IV. OBJECTIVES:  To
      evaluate surgical candidates with foraminal or extraforaminal lumbar disc
      herniation treated with CT-guided periradicular injection (CTGPI) as a valid
      treatment option for avoiding surgery. METHODS:  We carried out a retrospective
      evaluation of 46 consecutive patients with foraminal or extraforaminal disc
      herniation treated with CTGPI. CTGPI was performed only when radicular pain could
      not be controlled, or in patients who continued requiring pain medication
      following an acute episode and whose radicular pain precluded them from resuming
      their daily activities. Forty-six patients with a minimum 2-year follow-up met
      the inclusion criteria. There were 21 women and 25 men, with a mean age of 47
      years. RESULTS:  At 1 month after injection, 41 (89%) patients experienced a
      decrease in radicular pain; 3 experienced no change; and 2 had received surgical
      treatment. At the final follow-up visit (mean, 74 months) 6 additional patients
      underwent surgery while 38 (83%) did not require surgery. Pain level comparison
      between pre-injection and last examination showed that low back pain had
      decreased a mean of 5 points and radicular pain diminished a mean of 7 points.
      Twenty-two (58%) of the 38 nonoperated patients had no pain at all and 35
      patients had resumed their normal daily activities. No complications were
      recorded. CONCLUSION:  Based on these results, we consider that the use of CTGPI
      is a reliable alternative before surgery for patients with foraminal or
      extraforaminal disc herniation without severe motor deficit but with intractable
      radicular pain. [Table: see text].

PMID- 23532380
TI  - A two-tube multiplex real-time RT-PCR assay for the detection of four hemorrhagic
      fever viruses: severe fever with thrombocytopenia syndrome virus, Hantaan virus,
      Seoul virus, and dengue virus.
AB  - The aim of this study was to develop and evaluate a two-tube multiplex real-time
      RT-PCR assay for the detection and identification of four viral hemorrhagic fever
      (VHF) pathogens, severe fever with thrombocytopenia syndrome virus (SFTSV),
      Hantaan virus (HTNV), Seoul virus (SEOV), and dengue virus (DENV), from human
      clinical samples. The two-tube multiplex real-time RT-PCR assay we developed has
      a sensitivity of 10 copies/MUL for each of the targets, and the performance was
      linear within the range of at least 10(7) transcript copies. Moreover, we
      evaluated the specificity of the assay using other virus RNA as template, and
      found no cross-reactivity. This new assay is able to detect SFTSV, HTNV, SEOV and
      DENV in two reactions and brings a cost of 40 % compared to separate reactions.
      Evaluation of this assay with clinical serum samples from laboratory-confirmed
      patients and healthy donors showed 100 % clinical diagnostic sensitivity and over
      99 % specificity. The assay was applied for scanning 346 clinical samples
      collected from patients admitted to the hospital with suspected VHF and compared
      with virus isolation and immunofluorescence assay (IFA). The assay indentified 59
      SFTSV-, 12 HTNV-, 11 SEOV- and 9 DENV-positive samples and showed higher
      sensitivity. This assay thus provides a reliable and cost-effective screening
      tool for early clinical diagnosis of SFTSV, HTNV, SEOV and DENV in the acute
      phase. 

PMID- 23532381
TI  - Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild
      type TP53.
AB  - BACKGROUND: TP53 is one of the most widely known cancer suppressor genes.
      Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of
      mutations range from ~15-70 % in patients with hepatocellular carcinoma (HCC).
      Moreover, patients with mutated TP53 have poorer prognoses than those with wild
      type TP53; therefore, it would be beneficial to predict the prognosis of HCC
      patients with wild-type TP53. We previously reported that PICT1, coding a
      nucleolus protein, regulates TP53 through indirect association. METHODS: In this
      study, we examined PICT1 expression levels and the status of TP53 in 51 primary
      HCC tissues in order to determine the clinical significance of PICT1 expression
      and the function of PICT1 in HCC cells. RESULTS: We detected 6 mutations in the
      51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression
      (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and
      there were no significant associations with other clinicopathological factors.
      According to gene set enrichment analysis, PICT1 expression was inversely
      correlated with the gene set of TP53. In vitro assays indicated that suppression
      of PICT1 expression caused an increase in TP53 expression, reduction in cell
      proliferation, and arrest at the G1 phase of the cell cycle in HCC cells
      expressing wild-type TP53. CONCLUSIONS: PICT1 should be a useful prognostic
      marker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a
      promising therapeutic target because of its ability to increase the expression
      and activation of TP53.

PMID- 23532382
TI  - Prorenin receptor in distal nephron segments of 2-kidney, 1-clip goldblatt
      hypertensive rats.
AB  - BACKGROUND: The prorenin receptor (PRR) is expressed in the kidneys and has been
      localized to mesangial cells, renal arterioles, and distal nephron segments. By
      binding renin or prorenin, this receptor increases renin catalytic activity and
      activates prorenin. The renin gene is expressed by the principal cells of
      collecting ducts and is enhanced in angiotensin II (AngII)-dependent hypertension
      and in both kidneys of 2-kidney, 1-clip (2K1C) Goldblatt hypertensive rats.
      Colocalization of PRR with prorenin and renin in distal nephron segments may
      contribute to increased local AngII formation. METHODS: We examined the specific
      cell-type localization of PRR in distal nephron segments and the changes in PRR
      gene expression in both kidneys of 2K1C hypertensive rats (n=6) and sham-operated
      rats (n=5). RESULTS: After 25 days, systolic blood pressure and plasma renin
      activity increased to 186 +/- 8 mmHg and 12.8 +/- 3 ng/AngI/mL/hr, respectively,
      in 2K1C rats compared to controls (133 +/- 9 mmHg and 7.1 +/- 1 ng/AngI/mL/hr,
      respectively). Immunohistochemistry of the PRR on fixed kidney sections showed
      intense positive staining in the apical aspects of intercalated cells in
      collecting ducts. PRR immunoreactivity (clipped kidney: 2.3 +/- 1 IDU; nonclipped
      kidney: 1.3 +/- 0 IDU; sham: 1.0 +/- 0.0 IDU; P<0.05) and messenger RNA levels
      measured by quantitative real-time polymerase chain reaction (clipped kidney: 1.3
      +/- 0.1 au; nonclipped kidney: 0.9 +/- 0.3 au; sham: 1 +/- 0.0 au; P<0.05] were
      increased in collecting duct cells of clipped kidneys of 2K1C rats compared to
      nonclipped and sham kidneys. CONCLUSION: The enhanced renin gene expression in
      the collecting ducts of hypertensive rats suggests that the renin secreted by
      principal cells is then anchored by the PRR on the intercalated cells, thus
      contributing to increased angiotensin peptide generation in distal nephron
      segments.

PMID- 23532379
TI  - The role of nutrition in children's neurocognitive development, from pregnancy
      through childhood.
AB  - This review examines the current evidence for a possible connection between
      nutritional intake (including micronutrients and whole diet) and neurocognitive
      development in childhood. Earlier studies which have investigated the association
      between nutrition and cognitive development have focused on individual
      micronutrients, including omega-3 fatty acids, vitamin B12, folic acid, choline,
      iron, iodine, and zinc, and single aspects of diet. The research evidence from
      observational studies suggests that micronutrients may play an important role in
      the cognitive development of children. However, the results of intervention
      trials utilizing single micronutrients are inconclusive. More generally, there is
      evidence that malnutrition can impair cognitive development, whilst breastfeeding
      appears to be beneficial for cognition. Eating breakfast is also beneficial for
      cognition. In contrast, there is currently inconclusive evidence regarding the
      association between obesity and cognition. Since individuals consume combinations
      of foods, more recently researchers have become interested in the cognitive
      impact of diet as a composite measure. Only a few studies to date have
      investigated the associations between dietary patterns and cognitive development.
      In future research, more well designed intervention trials are needed, with
      special consideration given to the interactive effects of nutrients.

PMID- 23532383
TI  - Osteoconduction of porous Ti metal enhanced by acid and heat treatments.
AB  - Bone ingrowth into porous Ti metal is important for stable fixation of Ti metal
      implants to surrounding bone. However, without surface treatment this is limited
      to only a thin region of the outer surface of the Ti metal. In the present study,
      a porous Ti metal with a porosity of ~60 % and interpore connections of 70-200
      micrometers in diameter was investigated in terms of its chemical and heat
      treatments, by implanting it into rabbit femur for periods varying from 3 to 12
      weeks. The porous Ti metal subjected to heat treatment at 600  degrees C after
      H2SO4/HCl mixed acid treatment showed the largest bone ingrowth in comparison
      with those subjected to no treatment, only acid treatment, and only heat
      treatment even at an early stage after implantation, and remained as such even 12
      weeks after implantation. Their bone ingrowths were well interpreted in terms of
      apatite-forming abilities of the Ti metals in body environment. Their apatite
      forming abilities did not depend upon their surface roughness nor type of
      crystalline phase, but upon the positive surface charge. 

PMID- 23532384
TI  - Nanopatterned polymer brushes as switchable bioactive interfaces.
AB  - We report convenient methods for synthesis of nanopatterned, thermally responsive
      brushes of poly(N-isopropyl acrylamide) over large areas (e.g., 1 cm(2)) to form
      model, dynamic, biofunctional surfaces. The new nanopatterned brush structure can
      be used to control (i) the rate of both nonspecific and biospecific adsorption
      processes at the polymer-graft-free regions of the substrate, and (ii) the rate
      of cell detachment. These capabilities have potential implications in a number of
      areas of biotechnology including biosensing, separations and cell culture.

PMID- 23532385
TI  - Linkage mapping and molecular diversity at the flower sex locus in wild and
      cultivated grapevine reveal a prominent SSR haplotype in hermaphrodite plants.
AB  - Cultivars used for wine and table grape have self-fertile hermaphrodite flowers
      whereas wild European vines and American and Asian species are dioecious, having
      either male or female flowers. Consistent with previous studies, the flower sex
      trait was mapped as a single major locus on chromosome 2 based on a pure Vitis
      vinifera population segregating for hermaphrodite and female progeny, and a
      hybrid population producing all three flower sex types. The sex locus was placed
      between the same SSR and SNP markers on both genetic maps, although abnormal
      segregation hampered to fine map the genomic region. From a total of 55 possible
      haplotypes inferred for three SSR markers around the sex locus, in a population
      of 132 V. sylvestris accessions and 171 V. vinifera cultivars, one of them
      accounted for 66 % of the hermaphrodite individuals and may be the result of
      domestication. Specific size variants of the VVIB23 microsatellite sequence
      within the 3'-UTR of a putative YABBY1 gene were found to be statistically
      significantly associated with the sex alleles M, H and f; these markers can
      provide assistance in defining the status of wild grapevine germplasm.

PMID- 23532387
TI  - Progestogens for preterm birth prevention: a systematic review and meta-analysis
      by drug route.
AB  - PURPOSE: Progestogen has been investigated as a preventive intervention among
      women with increased preterm birth risk. Our objective was to systematically
      review the effectiveness of intramuscular (IM), vaginal, and oral progestogens
      for preterm birth and neonatal death prevention. METHODS: We included articles
      published from January 1966 to January 2013 and found 27 randomized trials with
      data for Bayesian meta-analysis. RESULTS: Across all studies, only vaginal and
      oral routes were effective at reducing preterm births (IM risk ratio [RR] 0.95,
      95 % Bayesian credible interval [BCI]: 0.88-1.03; vaginal RR 0.87, 95 % BCI: 0.80
      0.94; oral RR 0.64, 95 % BCI: 0.49-0.85). However, when analyses were limited to
      only single births all routes were effective at reducing preterm birth (IM RR
      0.77, 95 % BCI: 0.69-0.87; vaginal RR 0.80, 95 % BCI: 0.69-0.91; oral RR 0.66, 95
      % BCI: 0.47-0.84). Only IM progestogen was effective at reducing neonatal deaths
      (IM RR 0.78, 95 % BCI: 0.56-0.99; vaginal RR 0.75, 95 % BCI: 0.45-1.09; oral RR
      0.72, 95 % BCI: 0.09-1.74). Vaginal progestogen was effective in reducing
      neonatal deaths when limited to singletons births. CONCLUSIONS: All progestogen
      routes reduce preterm births but not neonatal deaths. Future studies are needed
      that directly compare progestogen delivery routes.

PMID- 23532386
TI  - Systematic optimization of multiplex zymography protocol to detect active
      cathepsins K, L, S, and V in healthy and diseased tissue: compromise among limits
      of detection, reduced time, and resources.
AB  - Cysteine cathepsins are a family of proteases identified in cancer,
      atherosclerosis, osteoporosis, arthritis, and a number of other diseases. As this
      number continues to rise, so does the need for low cost, broad use quantitative
      assays to detect their activity and can be translated to the clinic in the
      hospital or in low resource settings. Multiplex cathepsin zymography is one such
      assay that detects subnanomolar levels of active cathepsins K, L, S, and V in
      cell or tissue preparations observed as clear bands of proteolytic activity after
      gelatin substrate SDS-PAGE with conditions optimal for cathepsin renaturing and
      activity. Densitometric analysis of the zymogram provides quantitative
      information from this low cost assay. After systematic modifications to optimize
      cathepsin zymography, we describe reduced electrophoresis time from 2 h to 10
      min, incubation assay time from overnight to 4 h, and reduced minimal tissue
      protein necessary while maintaining sensitive detection limits; an evaluation of
      the pros and cons of each modification is also included. We further describe
      image acquisition by Smartphone camera, export to Matlab, and densitometric
      analysis code to quantify and report cathepsin activity, adding portability and
      replacing large scale, darkbox imaging equipment that could be cost prohibitive
      in limited resource settings.

PMID- 23532388
TI  - A local hemostatic agent for the management of postpartum hemorrhage due to
      placenta previa and placenta accreta: a cross-sectional study.
AB  - PURPOSE: To describe the use of a local hemostatic agent (LHA) for the management
      of postpartum hemorrhage (PPH) due to bleeding of the placental bed in patients
      taken to caesarean section at Fundacion Santa Fe de Bogota University Hospital.
      SAMPLE: A total of 41 pregnant women who had a caesarean section and developed
      PPH. METHODS: A cross-sectional study. Analysis of all cases of PPH during
      caesarean section presented from 2006 up to and including 2012 at Fundacion Santa
      Fe de Bogota University Hospital. MAIN OUTCOME MEASURE: Emergency hysterectomy
      due to PPH. RESULTS: The proportion of hysterectomies was 5 vs. 66 % for the
      group that received and did not receive management with a LHA respectively (PR
      0.07, CI 95 % 0.01-0.51 p < 0.01). For the group managed without a LHA, 80 % of
      patients needed hemoderivatives transfusion vs. 20 % of patients in the group
      managed with a LHA (PR 0.24, CI 95 % 0.1-0.6 p < 0.01). A reduction in the mean
      days of hospitalization in addition to a descent in the proportion of patients
      admitted to the intensive care unit (ICU) was noticed when comparing the group
      that received a LHA versus the one that did not. CONCLUSION: An inverse
      association between the use of a LHA in patients with PPH due to bleeding of the
      placental bed and the need to perform an emergency obstetric hysterectomy was
      observed. Additionally there was a significant reduction in the mean duration of
      hospital stay, use of hemoderivatives and admission to the ICU.

PMID- 23532389
TI  - The accessory fallopian tube: A rare anomaly.
AB  - This paper presents a rare anatomical variation in the form of accessory
      fallopian tube on right side. The duplication of fallopian tube was observed in a
      34-year-old female during routine undergraduate dissection in our department.
      Fallopian tube is the part of uterus that carries the ovum from the ovary to the
      uterus. Accessory fallopian tube is the congenital anomaly attached to the
      ampullary part of main tube. This accessory tube is common site of pyosalpinx,
      hydrosalpinx, cystic swelling and torsion. The ovum released by the ovary may
      also be captured by the blind accessory tube leading to infertility or ectopic
      pregnancy. Hence, all patients of infertility or pelvic inflammatory disease
      should be screened to rule out the presence of accessory fallopian tube and if
      encountered should be removed.

PMID- 23532390
TI  - Metabolomics for unknown plant metabolites.
AB  - In this article we discuss current trends in the techniques available for plant
      metabolomics. Chemical assignment of unknown metabolites leads to understanding
      of biosynthetic mechanisms at the gene level for genome-sequenced plants.
      Metabolomics using mass spectrometry has achieved innovative results in
      phytochemical genomics for primary and secondary metabolism in the model plant
      Arabidopsis thaliana by using publicly and commercially available information and
      standard compounds. However, finding a consolidated analytical technique for
      elucidation of structural information (e.g., elemental composition and structure)
      remains challenging. Recently, hyphenated analytical techniques and computer
      assisted structural analysis with high-throughput and high-accuracy have been
      developing. Metabolite-driven approaches using such technology will be of central
      importance in phytochemical genomics.

PMID- 23532391
TI  - Uptake and release kinetics of 22 polar organic chemicals in the Chemcatcher
      passive sampler.
AB  - The Chemcatcher passive sampler, which uses EmporeTM disks as sampling phase, is
      frequently used to monitor polar organic chemicals in river water and effluents.
      Uptake kinetics need to be quantified to calculate time-weighted average
      concentrations from Chemcatcher field deployments. Information on release
      kinetics is needed if performance reference compounds (PRCs) are used to quantify
      the influence of environmental conditions on the uptake. In a series of uptake
      and elimination experiments, we used EmporeTM SDB disks
      (poly(styrenedivinylbenzene) copolymer modified with sulfonic acid groups) as a
      sampling phase and 22 compounds with a logK(ow) (octanol-water partitioning
      coefficient) range from -2.6 to 3.8. Uptake experiments were conducted in river
      water or tap water and lasted up to 25 days. Only 1 of 22 compounds
      (sulfamethoxazole) approached equilibrium in the uptake trials. Other compounds
      showed continuing non-linear uptake, even after 25 days. All compounds could be
      released from SDB disks, and desorption was proportionally higher in disks loaded
      for shorter periods. Desorption showed two-phase characteristics, and desorption
      was proportionally higher for passively sorbed compounds compared to actively
      loaded compounds (active loading was performed by pulling spiked river water over
      SDB disks using vacuum). We hypothesise that the two-phase kinetics and better
      retention of actively loaded compounds--and compounds loaded for a longer period-
      may be caused by slow diffusion of chemicals within the polymer. As sorption and
      desorption did not show isotropic kinetics, it is not possible to develop robust
      PRCs for adsorbent material like SDB disks.

PMID- 23532392
TI  - Detection and quantification of proteins and cells by use of elemental mass
      spectrometry: progress and challenges.
AB  - Much progress has been made in identification of the proteins in proteomes, and
      quantification of these proteins has attracted much interest. In addition to
      popular tandem mass spectrometric methods based on soft ionization, inductively
      coupled plasma mass spectrometry (ICPMS), a typical example of mass spectrometry
      based on hard ionization, usually used for analysis of elements, has unique
      advantages in absolute quantification of proteins by determination of an element
      with a definite stoichiometry in a protein or attached to the protein. In this
      Trends article, we briefly describe state-of-the-art ICPMS-based methods for
      quantification of proteins, emphasizing protein-labeling and element-tagging
      strategies developed on the basis of chemically selective reactions and/or
      biospecific interactions. Recent progress from protein to cell quantification by
      use of ICPMS is also discussed, and the possibilities and challenges of ICPMS
      based protein quantification for universal, selective, or targeted quantification
      of proteins and cells in a biological sample are also discussed critically. We
      believe ICPMS-based protein quantification will become ever more important in
      targeted quantitative proteomics and bioanalysis in the near future. 

PMID- 23532393
TI  - Impact of homogeneous and filamentary discharge modes on the efficiency of
      dielectric barrier discharge ionization mass spectrometry.
AB  - The present study contributes to the evaluation of dielectric barrier discharge
      based ambient ionization for mass spectrometric analysis (DBDI-MS) by providing a
      further step towards an understanding of underlying ionization processes. This
      examination highlights the effect of physical discharge modes on the ionization
      efficiency of the DBDI source. A distinction is made between the homogeneous and
      filamentary discharge mode due to different plasma gases in barrier
      configurations. Therefore, we first report on discharge modes of DBDI by
      demonstrating a universally applicable method to classify the predominant modes.
      Then, the ionization efficiency of these two modes is evaluated by a laser
      desorption-DBDI-MS with different molecular analytes. Here, the laser desorption
      is used to deliver neutral analytes which will be ionized by the plasma jet
      applied as dielectric barrier discharge ionization. With a clear increase of
      signal intensities in the homogeneous mode in contrast to the filamentary one,
      the present study indicates a pronounced dependence of the ionization efficiency
      on the discharge mode allowing further insight into the mechanisms of the
      ionization process.

PMID- 23532394
TI  - Phenylvinylcobalamin: an alkenylcobalamin featuring a ligand with a large trans
      influence.
AB  - Cob(I)alamin reacts with phenylacetylene to produce two diastereomers in which
      the organic ligand is coordinated to the upper (beta) and lower (alpha) face of
      the corrin ring, respectively. The isomers were separated chromatographically and
      characterised by ESI-MS and, in the case of the beta isomer, by (1)H and (13)C
      NMR. Only the beta isomer crystallised and its molecular structure, determined by
      X-ray diffraction, shows that the organic ligand coordinates Co(III) through the
      beta carbon of the phenylvinyl ligand. The Co-C bond length is 2.004(8) A while
      the Co-N bond length to the trans 5,6-dimethylbenzimidazole (dmbzm) base is
      2.217(8) A, one of the longest Co-Ndmbzm bond lengths known in an
      organocobalamin. Unlike benzylcobalamin (BzCbl), phenylvinylcobalamin (PhVnCbl)
      is stable towards homolysis. DFT calculations (BP86/TZVP) on model compounds of
      BzCbl and PhVnCbl show that the Co-C bond dissociation energy for homolysis to
      Co(II) and an organic radical in the former is 8 kcal mol(-1) lower than in the
      latter. An analysis of the electron density at the Co-C bond critical point using
      Bader's QTAIM approach shows that the Co-C bond in PhVnCbl is shorter, stronger
      and somewhat more covalent than that in BzCbl, and has some multiple bond
      character. Together with calculations that show that the benzyl radical is more
      stable than the phenylvinyl radical, this rationalises the stability of PhVnCbl
      compared to BzCbl. The phenylvinyl ligand has a large trans influence. The pKa
      for deprotonation of dmbzm and its coordination by the metal in beta-PhVnCbl is
      4.60 +/- 0.01, one of the highest values reported to date in cobalamin chemistry.
      The displacement of dmbzm ligand by CN(-) in beta-PhVnCbl occurs with log K = 0.7
      +/- 0.1; the trans influence order of C-donor ligands is therefore CN(-) < CCH <
      CHCH2 = PhVn < Me < Et.

PMID- 23532395
TI  - Personalized therapy in gynecological cancer: a reality in clinical practice?

PMID- 23532396
TI  - Antagonism of the histamine H4 receptor reduces LPS-induced TNF production in
      vivo.
AB  - OBJECTIVE: Antagonism of the histamine H4 receptor (H4R) has been shown to be
      anti-inflammatory in a number of preclinical disease models, however the exact
      mechanisms behind this are still being uncovered. In vitro, the receptor
      interacts with TLR and impacts inflammatory mediator production from a number of
      different cell types. Here it is shown that this interaction also occurs in vivo.
      MATERIALS AND METHODS: Wild-type and H4R deficient BALB/c mice received an i.p.
      injection of LPS in PBS in conjunction with p.o. JNJ 7777120 or JNJ 28307474 (H4R
      antagonists). Two hours later blood was collected and TNF was measured. RESULTS:
      Two different H4R antagonists inhibited LPS-induced TNF production in mice and
      this production was also reduced in H4R-deficient mice. The TNF mRNA analysis
      showed that the major source of the cytokine was the liver and not blood, and
      that the H4R antagonist only reduced the expression levels in the liver.
      Depletion or inactivation of macrophages reduced the TNF levels and eliminated
      the H4R sensitivity. Treatment with an H4R antagonist also reduced LPS-induced
      liver injury and blocked LPS-enhanced lung inflammation in mice. CONCLUSION: The
      data support an interaction between H4R and TLR activation in vivo that can drive
      inflammatory responses.

PMID- 23532397
TI  - A description of common mental disorders in men who have sex with men (MSM)
      referred for assessment and intervention at an MSM clinic in Cape Town, South
      Africa.
AB  - Men who have sex with men (MSM) have a higher prevalence of common mental
      disorders (CMD), as compared with heterosexual men. HIV infection is
      independently associated with higher rates of CMD. Given this context, and the
      high background community prevalence of HIV in South Africa, MSM are at even
      greater risk of developing CMD. The aim of this research was to investigate
      neuropsychiatric symptoms and disorders in MSM who were referred for assessment
      and management of mental health problems, in an MSM Clinic in urban Cape Town,
      South Africa. Twenty-five men were screened using the MINI, AUDIT, DUDIT, and
      IPDE Screener. Depression, suicidality, as well as alcohol and drug use disorders
      were highly prevalent in this group (44, 56, 48, and 56 % respectively). The
      personality disorder screening was suggestive of a high prevalence of personality
      disorders. The high prevalence of neuropsychiatric disorders in this sample
      supports the idea that integrated mental health services are needed to address
      the complex needs of this population. Adequate input into the mental health needs
      of this population could reduce the potential for HIV acquisition and
      transmission, improve adherence to treatment and care, and ensure the provision a
      comprehensive health service for MSM.

PMID- 23532398
TI  - Measuring prevalence and correlates of concurrent sexual partnerships among young
      sexually active men in Kisumu, Kenya.
AB  - Our objectives were to: (1) compare multiple measures of partnership concurrency,
      including the UNAIDS-recommended definition and (2) describe the prevalence and
      correlates of concurrent sexual partnerships among young Kenyan men. We analyzed
      10,907 lifetime partnerships of 1,368 men ages 18-24 years enrolled in a
      randomized trial of male circumcision to reduce HIV-1 incidence in Kisumu.
      Partnership concurrency was determined by overlapping dates and examined over
      varying recall periods and assumptions. The lifetime prevalence of concurrency
      was 77 %. Sixty-one percent of all partnerships were concurrent and factors
      associated with concurrency differed by partner type. Point prevalence of
      concurrency at the time of the interview was consistently the highest and UNAIDS
      recommended definition was the most conservative (25 vs. 18 % at baseline,
      respectively). Estimates of concurrency were influenced by methods for definition
      and measurement. Regardless of definition, concurrent partnerships are frequent
      in this population of young, sexually active men in high HIV prevalence Kisumu,
      Kenya.

PMID- 23532399
TI  - UV protection of reduced graphene oxide films by TiO2 nanoparticle incorporation.
AB  - A simple strategy for preparation of reduced graphene oxide (RGO)/TiO2 hybrid
      thin films was developed by UV-assisted incorporation of TiO2 nanoparticles (NPs)
      onto RGO films. The UV-assisted incorporation of TiO2 NPs onto RGO films makes
      the hybrid films stable against prolonged exposure to UV light without the
      decrease of their conductivity and transparency.

PMID- 23532400
TI  - Prevalence and predictors of posttraumatic stress disorder and depressive
      symptoms among child survivors 1 year following the Wenchuan earthquake in China.
AB  - The purpose of this study was to estimate the prevalence rates of probable
      posttraumatic stress disorder (PTSD) and depression and to explore potential risk
      factors among child and adolescent survivors 1 year following the 2008 Wenchuan
      earthquake. 3052 participants were administered the Child PTSD Symptom Scale, the
      Center for Epidemiologic Studies Depression Scale for Children, and the
      earthquake experience scale. Results indicated that the prevalence rates of
      probable PTSD and depression were 8.6 and 42.5%, respectively. Demographic
      variables (i.e., age and gender) and most aspects of earthquake experiences
      (i.e., direct exposure, close ones' exposure, fear for the safety of close ones,
      prior exposure to trauma, living location, and house damage, with the exception
      of type of housing) made unique contributions to PTSD and depressive symptoms. In
      addition, the moderating effect of gender on the relationships between age and
      PTSD and depressive symptoms was significant. In conclusion, depression was a
      more common psychological response than was PTSD among child survivors 1 year
      following the Wenchuan earthquake. Age and gender were risk factors for both PTSD
      and depressive symptoms. Furthermore, older female survivors exhibit more severe
      PTSD and depressive symptoms. Additionally, several aspects of earthquake
      experiences (i.e., direct exposure, close ones' exposure, fear for the safety of
      close ones, prior exposure to trauma, living location, and house damage) was also
      important for the development and maintenance of PTSD and depressive symptoms.

PMID- 23532401
TI  - Early gene expression divergence between allopatric populations of the house
      mouse (Mus musculus domesticus).
AB  - Divergence of gene expression is known to contribute to the differentiation and
      separation of populations and species, although the dynamics of this process in
      early stages of population divergence remains unclear. We analyzed gene
      expression differences in three organs (brain, liver, and testis) between two
      natural populations of Mus musculus domesticus that have been separated for at
      most 3000 years. We used two different microarray platforms to corroborate the
      results at a large scale and identified hundreds of genes with significant
      expression differences between the populations. We find that although the three
      tissues have similar number of differentially expressed genes, brain and liver
      have more tissue-specific genes than testis. Most genes show changes in a single
      tissue only, even when expressed in all tissues, supporting the notion that
      tissue-specific enhancers act as separable targets of evolution. In terms of
      functional categories, in brain and to a smaller extent in liver, we find
      transcription factors and their targets to be particularly variable between
      populations, similar to previous findings in primates. Testis, however, has a
      different set of differently expressed genes, both with respect to functional
      categories and overall correlation with the other tissues, the latter indicating
      that gene expression divergence of potential importance might be present in other
      datasets where no differences in fraction of differentially expressed genes were
      reported. Our results show that a significant amount of gene expression
      divergence quickly accumulates between allopatric populations.

PMID- 23532402
TI  - Hospice patient evacuation: a case for using a checklist for safe disaster
      response.
AB  - This study was conducted to provide lessons learned from the experience of a
      small, rural hospice care organization to an actual crisis that required
      evacuation of the facility. A process improvement framework using the emergency
      response certification guidelines was used to first provide details of the
      incident, second analyze the effectiveness of disaster planning and response in
      response to an actual crisis, and third discuss the post-event review, lessons
      learned, and process improvement. This case study revealed 5 emerging themes
      disaster can happen at the most inopportune times, facilities should focus on the
      most likely hazards, written agreements are needed even in small tight-knit
      communities, redundancy of resources is needed, and disaster planning and
      response is a process that should be continually improved.

PMID- 23532403
TI  - Neuromodulation and palliative medicine.
AB  - The palliative care population is generally vulnerable to experiencing medication
      induced adverse effects and drug-drug interactions. Neuromodulation may offer
      particular advantages over systemic medications in this population. Spinal cord
      stimulation and peripheral nerve stimulation have long been utilized in efforts
      to provide analgesia for various painful conditions. More recently, deep brain
      stimulation/motor cortex stimulation has anecdotally been utilized for certain
      intractable pain states. Although brain electrical stimulation has not been
      adequately trialed or in some cases even tried at all for management of a variety
      of symptoms, it is conceivable that in the future it may be a potential
      therapeutic option in efforts to palliate various severe refractory symptoms (eg,
      intractable pain, nausea, dyspnea, delirium). 

PMID- 23532404
TI  - Methods for improving the quality of palliative care delivery: a systematic
      review.
AB  - BACKGROUND: The effectiveness for improving the outcomes across palliative care
      domains remains unclear. We conducted a systematic review of different types of
      quality improvement interventions relevant to palliative care. METHODS: We
      searched PubMed, CINAHL, PsycINFO, and Cochrane for relevant articles published
      between 2000 and 2011. RESULTS: A total of 10 randomized controlled trials and 7
      nonrandomized controlled trials were included. Of the 5 studies using relay of
      clinical information, 1 reported significant improvement in patient quality of
      life. Of the 5 studies targeting education and self-management, 4 found
      significant improvements in quality of life or patient symptoms. CONCLUSION: A
      minority of quality improvement interventions have succeeded in improving the
      quality of palliative care delivery. More studies are needed on specific quality
      improvement types, including organizational change and multiple types of
      interventions.

PMID- 23532405
TI  - Biophysical regulation of stem cell differentiation.
AB  - Bone adaptation to its mechanical environment, from embryonic through adult life,
      is thought to be the product of increased osteoblastic differentiation from
      mesenchymal stem cells. In parallel with tissue-scale loading, these
      heterogeneous populations of multipotent stem cells are subject to a variety of
      biophysical cues within their native microenvironments. Bone marrow-derived
      mesenchymal stem cells-the most broadly studied source of osteoblastic
      progenitors-undergo osteoblastic differentiation in vitro in response to
      biophysical signals, including hydrostatic pressure, fluid flow and accompanying
      shear stress, substrate strain and stiffness, substrate topography, and
      electromagnetic fields. Furthermore, stem cells may be subject to indirect
      regulation by mechano-sensing osteocytes positioned to more readily detect these
      same loading-induced signals within the bone matrix. Such paracrine and
      juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further
      studies are needed to confirm both direct and indirect mechanisms of biophysical
      regulation within the in vivo stem cell niche.

PMID- 23532406
TI  - Fibrous dysplasia and fibroblast growth factor-23 regulation.
AB  - Fibrous dysplasia (FD) is a skeletal disorder caused by activating mutations in
      Gsalpha that result in elevations in cAMP. A feature of FD is elevated blood
      levels of the bone cell-derived phosphaturic hormone, fibroblast growth factor-23
      (FGF23). FGF23 regulates serum phosphorus and active vitamin D levels by action
      on proximal renal tubule cells. An essential step in the production of
      biologically active FGF23 is glycosylation by the UDP-N-acetyl-alpha-D
      galactosamine:polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T3). In
      the absence of glycosylation, FGF23 is processed into inactive N- and C-terminal
      proteins by a subtilisin proprotein convertase, probably furin. Normally, most if
      not all circulating FGF23 is intact. In FD, C-terminal levels are elevated,
      suggesting altered FGF23 processing. Altered processing in FD is the result of a
      cAMP-dependent, coordinated decrease in ppGalNAc-T3 and an increase in furin
      enzyme activity. These findings, and emerging data from other diseases, suggest
      regulation of FGF23 processing may be a physiologically important process.

PMID- 23532407
TI  - Transgene delivery via intracellular electroporetic nanoinjection.
AB  - Development of an effective cytoplasmic delivery technique has remained an
      elusive goal for decades despite the success of pronuclear microinjection.
      Cytoplasmic injections are faster and easier than pronuclear injection and do not
      require the pronuclei to be visible; yet previous attempts to develop cytoplasmic
      injection have met with limited success. In this work we report a cytoplasmic
      delivery method termed intracellular electroporetic nanoinjection (IEN). IEN is
      unique in that it manipulates transgenes using electrical forces. The
      microelectromechanical system (MEMS) uses electrostatic charge to physically pick
      up transgenes and place them in the cytoplasm. The transgenes are then propelled
      through the cytoplasm and electroporated into the pronuclei using electrical
      pulses. Standard electroporation of whole embryos has not resulted in transgenic
      animals, but the MEMS device allows localized electroporation to occur within the
      cytoplasm for transgene delivery from the cytoplasm to the pronucleus. In this
      report we describe the principles which allow localized electroporation of the
      pronuclei including: the location of mouse pronuclei between 21 and 28 h post-hCG
      treatment, modeling data predicting the voltages needed for localized
      electroporation of pronuclei, and data on electric-field-driven movement of
      transgenes. We further report results of an IEN versus microinjection comparative
      study in which IEN produced transgenic pups with viability, transgene
      integration, and expression rates statistically comparable to microinjection. The
      ability to perform injections without visualizing or puncturing the pronuclei
      will widely benefit transgenic research, and will be particularly advantageous
      for the production of transgenic animals with embryos exhibiting reduced
      pronuclear visibility. 

PMID- 23532408
TI  - Key role of ERK1/2 molecular scaffolds in heart pathology.
AB  - The ability of cardiomyocytes to detect mechanical and humoral stimuli is
      critical for adaptation of the myocardium in response to new conditions and for
      sustaining the increased workload during stress. While certain stimuli mediate a
      beneficial adaptation to stress conditions, others result in maladaptive
      remodelling, ultimately leading to heart failure. Specific signalling pathways
      activating either adaptive or maladaptive cardiac remodelling have been
      identified. Paradoxically, however, in a number of cases, the transduction
      pathways involved in such opposing responses engage the same signalling proteins.
      A notable example is the Raf-MEK1/2-ERK1/2 signalling pathway that can control
      both adaptive and maladaptive remodelling. ERK1/2 signalling requires a
      signalosome complex where a scaffold protein drives the assembly of these three
      kinases into a linear pathway to facilitate their sequential phosphorylation,
      ultimately targeting specific effector molecules. Interestingly, a number of
      different Raf-MEK1/2-ERK1/2 scaffold proteins have been identified, and their
      role in determining the adaptive or maladaptive cardiac remodelling is a
      promising field of investigation for the development of therapeutic strategies
      capable of selectively potentiating the adaptive response.

PMID- 23532410
TI  - Cyanobacteria: potential candidates for drug discovery.
AB  - Cyanobacteria are a rich source of vast array of bioactive molecules including
      toxins with wide pharmaceutical importance. They show varied bioactivities like
      antitumor, antiviral, antibacterial, antifungal, antimalarial, antimycotics,
      antiproliferative, cytotoxicity, immunosuppressive agents and multi-drug
      resistance reversers. A number of techniques are now developed and standardized
      for the extraction, isolation, detection and purification of cyanobacterial
      bioactive molecules. Some of the compounds are showing interesting results and
      have successfully reached to phase II and phase III of clinical trials. These
      compounds also serve as lead compounds for the development of synthetic analogues
      with improved bioactivity. Cyanobacterial bioactive molecules hold a bright and
      promising future in scientific research and great opportunity for drug discovery.
      This review mainly focuses on anticancerous, antiviral and antibacterial
      compounds from cyanobacteria; their clinical status; extraction and detection
      techniques.

PMID- 23532409
TI  - Molecular and cellular pathogenesis of melanoma initiation and progression.
AB  - Melanoma is a malignant tumor of melanocytes that can spread to other organs of
      the body, resulting in severe and/or lethal malignancies. Melanocytes are pigment
      producing cells found in the deep layer of the epidermis and are originated from
      melanocytes stem cells through a cellular process called melanogenesis. Several
      genes and epigenetic and micro-environmental factors are involved in this process
      via the regulation and maintenance of the balance between melanocytes stem cells
      proliferation and their differentiation into melanocytes. Dysregulation of this
      balance through gain or loss of function of key genes implicated in the control
      and regulation of cell cycle progression and/or differentiation results in
      melanoma initiation and progression. This review aims to provide a comprehensive
      overview about the origin of melanocytes, the oncogenic events involved in
      melanocytes stem cells transformation, and the mechanisms implicated in the
      perpetuation of melanoma malignant phenotype.

PMID- 23532411
TI  - Next-generation sequencing-based transcriptome profiling analysis of Pohlia
      nutans reveals insight into the stress-relevant genes in Antarctic moss.
AB  - Genome-wide characterization of the Pohlia nutans transcriptome is essential for
      clarifying the role of stress-relevant genes in Antarctic moss adapting to the
      extreme polar environment. High-throughput Illumina sequencing was used to
      analyze the gene expression profile of P. nutans after cold treatment. A total of
      93,488 unigenes, with an average length of 405 bp, were obtained. Gene annotation
      showed that 16,781 unigenes had significant similarity to known functional
      protein-coding genes, most of which were annotated using the GO, KOG and KEGG
      pathway databases. Global profiling of the differentially expressed genes
      revealed that 3,796 unigenes were significantly upregulated after cold treatment,
      while 1,405 unigenes were significantly downregulated. In addition, 816 receptor
      like kinases and 1,309 transcription factors were identified from P. nutans. This
      overall survey of transcripts and stress-relevant genes can contribute to
      understanding the stress-resistance mechanism of Antarctic moss and will
      accelerate the practical exploitation of the genetic resources for this organism.

PMID- 23532413
TI  - Defective TiO2 with oxygen vacancies: synthesis, properties and photocatalytic
      applications.
AB  - Titanium dioxide (TiO2), as an important semiconductor metal oxide, has been
      widely investigated in the field of photocatalysis. The properties of TiO2,
      including its light absorption, charge transport and surface adsorption, are
      closely related to its defect disorder, which in turn plays a significant role in
      the photocatalytic performance of TiO2. Among all the defects identified in TiO2,
      oxygen vacancy is one of the most important and is supposed to be the prevalent
      defect in many metal oxides, which has been widely investigated both by
      theoretical calculations and experimental characterizations. Here, we give a
      short review on the existing strategies for the synthesis of defective TiO2 with
      oxygen vacancies, and the defect related properties of TiO2 including structural,
      electronic, optical, dissociative adsorption and reductive properties, which are
      intimately related to the photocatalytic performance of TiO2. In particular,
      photocatalytic applications with regard to defective TiO2 are outlined. In
      addition, we offer some perspectives on the challenge and new direction for
      future research in this field. We hope that this tutorial minireview would
      provide some useful contribution to the future design and fabrication of
      defective semiconductor-based nanomaterials for diverse photocatalytic
      applications.

PMID- 23532412
TI  - Effects of intracellular Mn on the radiation resistance of the halophilic
      archaeon Halobacterium salinarum.
AB  - Ionizing radiation (IR) is of particular interest in biology because its exposure
      results in severe oxidative stress to the cell's macromolecules. Our recent work
      with extremophiles supports the idea that IR resistance is most likely achieved
      by a metabolic route, effected by manganese (Mn) antioxidants. Biochemical
      analysis of "super-IR resistant" mutants of H. salinarum, evolved over multiple
      cycles of exposure to high doses of IR, confirmed the key role for Mn
      antioxidants in the IR resistance of this organism. Analysis of the proteome of
      H. salinarum "super-IR resistant" mutants revealed increased expression for
      proteins involved in energy metabolism, replenishing the cell with reducing
      equivalents depleted by the oxidative stress inflicted by IR. Maintenance of
      redox homeostasis was also activated by the over-expression of coenzyme
      biosynthesis pathways involved in redox reactions. We propose that in H.
      salinarum, increased tolerance to IR is a combination of metabolic regulatory
      adjustments and the accumulation of Mn-antioxidant complexes.

PMID- 23532414
TI  - 50 years of Radiation and Environmental Biophysics: what were the hallmark
      papers?

PMID- 23532415
TI  - Editorial on the first issue of Urolithiasis.

PMID- 23532416
TI  - A rapid food screener ranks potential renal acid load of renal stone formers
      similarly to a diet history questionnaire.
AB  - Dietary acid load was reported to be inversely related to urinary citrate
      excretion. The calcium renal stone formers (RSFs) should be recommended to lower
      their dietary potential renal acid load (PRAL) to reduce stone recurrence.
      Reduction of dietary PRAL also showed a promising role for the prevention of
      other metabolic diseases. However, clinicians often fail to provide nutritional
      screening and counseling due to lack of simple tools to obtain a reliable dietary
      history. A one-page food screener (LAKE score) was recently designed to obtain a
      reliable measure of dietary PRAL in short time. We report the testing of such an
      instrument in the evaluation of PRAL: in a population of 135 healthy subjects (60
      males, 75 females; age range 18-73), living in the area of Milan, Italy. Each
      participant received both the one-page LAKE food screener and an extensive 24-h
      dietary questionnaire. We examined agreement between the LAKE food screener
      scores, and estimates of PRAL and other nutrients produced by the computerized
      processing of thorough 24-h dietary histories. Spearman rank order correlation
      coefficient (r > 0.50) showed that LAKE score ranked subjects quite well with
      respect to dietary PRAL. LAKE positive subscore ranked patients with respect to
      dietary intake of total protein (r = 0.642) and phosphate (r = 0.648). We also
      obtained an excellent correlation of LAKE negative subscore with potassium intake
      (r = -0.531) and vitamin C (r = -0.554) as estimated by 24 h recalls. The LAKE
      score ranked patients similar to the estimates of 24-h dietary recalls, used as
      the "gold standard" for the evaluation of dietary PRAL. This rapid, simple and
      inexpensive food screener for the evaluation of dietary PRAL could provide a
      "snapshot" of the diet of the RSFs to allow an immediate feedback to the patient
      during office consultation.

PMID- 23532417
TI  - Metabolic risk factors and the effect of metaphylaxis in pediatric stone disease
      with hypocitraturia.
AB  - To describe the metabolic risk factors and investigate the effect of prophylaxis
      based on these factors on long-term recurrence of urolithiasis in pediatric
      patients with hypocitraturia. One-hundred and twenty-nine pediatric patients who
      underwent percutaneous nephrolithotomy between January 2008 and June 2011 were
      evaluated for metabolic risk factors. The patients with hypocitraturia were
      enrolled in this study and the data were analyzed using statistical methods for a
      mean period of 2 years for metabolic abnormalities, stone type, and the effect of
      potassium citrate prophylaxis on stone recurrence. A 24-h urine metabolite
      analysis revealed one or more metabolic risk factors in 115 (89.2 %) of the
      patients, whereas 14 (10.8 %) of the patients had no metabolic abnormalities.
      Eighty-two (63.5 %) of 129 patients had hypocitraturia. Of them, 43 (52 %) were
      male and 39 (48 %) were female, with a mean age of 9.7 +/- 4.9 and 6.7 +/- 4.4 (1
      16) years, respectively(p = 0.102). Thirty-five (42.7 %) had pure hypocitraturia,
      and 47 (57.3 %) had two or more metabolic abnormalities. The most common dual
      metabolic abnormality was hypocitraturia and hypomagnesuria. Seventy-one patients
      (87 %) with hypocitraturia received medical prophylaxis and continued regularly,
      whereas 11 (13 %) patients did not receive medical prophylaxis despite being
      advised to do so. After a mean follow-up of 26.5 +/- 9.4 months, the rate of
      recurrence was 1.4 % in the patients with hypocitraturia who continued
      prophylaxis and occurred in all of the patients who did not receive prophylaxis
      (p < 0.001). Calcium oxalate stones (95.2 %) were the most commonly found stones
      in the stone analysis. Detailed clinical and laboratory evaluations should be
      performed in children with urolithiasis. Appropriate prophylactic treatment as
      potassium citrate, should be given to prevent reformation of stones in patient
      with hypocitraturia.

PMID- 23532418
TI  - Effect of different brewing times on soluble oxalate content of loose-packed
      black teas and tea bags.
AB  - Because of the postulated role of increased dietary oxalate intake in calcium
      oxalate stone formation, the effect of different brewing times on soluble oxalate
      contents of loose-packed black tea and tea bags was studied. The oxalate content
      of 25 different samples of loose-packed black teas after brewing at 5, 10, 15,
      30, and 60 min and of ten brands of tea bags after infusion for 1, 2, 3, 4, and 5
      min was measured by enzymatic assay. The oxalate concentration resulting from
      different brewing times ranged from 4.3 to 6.2 mg/240 ml for loose-packed black
      teas and from 2.7 to 4.8 mg/240 ml for tea bags. There was a stepwise increase in
      oxalate concentration associated with increased brewing times.

PMID- 23532419
TI  - Molecular characterization of cystinuria in south-eastern European countries.
AB  - Cystinuria is an autosomal recessive disorder caused by defective transport of
      cystine and dibasic amino acids in the proximal renal tubules and small
      intestine. So far, more than 128 mutations in SLC3A1 gene, and 93 in SLC7A9 gene
      have been described as a cause of cystinuria. We present a molecular
      characterization of the cystinuria in 47 unrelated south-east European families.
      The molecular methodology included direct sequencing, single strand
      conformational polymorphism, and restriction fragment length polymorphism. A
      total of 93 (94.9 %) out of 98 unrelated cystinuric chromosomes have been
      characterized. Mutations in SLC3A1 gene account for 64.3 % and in SLC7A9 gene for
      30.6 % of the cystinuric chromosomes. Ten different mutations in SLC3A1 gene were
      found, and two of them were novel (C242R and L573X), while in SLC7A9 gene seven
      mutations were found, of which three were novel (G73R, V375I and
      c.1048_1051delACTC). The most common mutations in this study were T216M (24.5 %),
      M467T (16.3 %) and R365L (11.2 %) in SLC3A1 and G105R (21.4 %) in SLC7A9 gene. A
      population specificity of cystinuria mutations was observed; T216M mutation was
      the only mutation present among Gypsies, G105R was the most common mutation among
      Albanians and Macedonians, and R365L among Serbs. The results of this study
      allowed introduction of rapid, simple and cost-effective genetic diagnosis of
      cystinuria that enables an early preventive care of affected patients and a
      prenatal diagnosis in affected families.

PMID- 23532420
TI  - Early ureteral catheter removal after ureteroscopic lithotripsy using ureteral
      access sheath.
AB  - A ureteral access sheath (UAS) can facilitate ureteroscopy (URS) and the
      retrieval of stone fragments while reducing the intrarenal pressure, thereby
      improving irrigate flow and decreasing the length of an operation. Ureteral
      stenting after URS is unnecessary for uncomplicated cases. This study examined
      the early removal of postoperative ureteral catheterization after URS for cases
      that used a UAS. A total of 93 patients underwent ureteroscopic lithotripsy with
      the early removal of ureteral catheterization. Sixty-three of these patients
      underwent surgery with the use of UAS and were analyzed in this study.
      Postoperative hydronephrosis was assessed using ultrasonography 3 days after the
      operation and computed tomography 2 weeks after operation in all patients. Post
      operative complications including fever, prolonged hospitalization, frequent
      usage of painkillers and the re-insertion of ureteral stent were also
      investigated. Hydronephrosis was detected 3 days after the operation in 34
      patients (54.0 %) and 2 weeks after the operation in four patients (6.3 %). No
      hydronephrosis was detected after a 2-month follow-up in these four patients. The
      mean operation time in the hydronephrosis group was significantly higher at 58.9
      min than in the non-hydronephrosis group at 45.5 min (p < 0.05). Post-operative
      fever (38  degrees C) was seen in one case, the frequent usage of painkillers was
      seen in four cases, a prolonged hospital stay was seen in five cases, and
      ureteral stent re-insertion was observed in one case. The early removal of
      ureteral catheterization can be safely performed for the patients that undergo
      URS with UAS.

PMID- 23532421
TI  - Effectiveness and safety of ureteroscopy in pregnant women: a comparative study.
AB  - The aim of this study was to investigate the efficacy and safety of ureteroscopy
      (URS) in pregnant patients compared with non-pregnant patients. We reviewed the
      cases of 41 pregnant and 62 non-pregnant women who developed ureteral stones and
      were treated with URS in our center between April 2005 and September 2011. A semi
      rigid 9.5 F ureteroscope was used. The calculi were fragmented with pneumatic
      lithotripsy or a holmium laser, and if necessary, a double-J (JJ) stent was
      inserted during the procedure. Among the pregnant women, the mean gestation
      period was 23.22 +/- 4.61 weeks (range 13-34), and the mean number of pregnancies
      per patient was 3 +/- 2.02 (range 1-10). The mean ages of the pregnant and non
      pregnant patients were 27.41 +/- 5.79 and 28.54 +/- 7.94 years, respectively (p =
      0.734). There were no statistically significant differences in stone
      localization, anesthesia type, stone diameter, methods of stone manipulation, JJ
      stent insertion rate, hospitalization length, or operative times between the two
      groups. For pregnant and non-pregnant patients, the stone-free rates achieved in
      a single session were 87.8 and 85.5 %, respectively (p = 0.737). There was no
      statistically significant difference in preoperative and postoperative
      complication rates between the two groups. The positive urine culture rate was
      statistically significantly higher for pregnant patients than non-pregnant
      patients (29.3 vs. 11.3 %; p = 0.021). We did not observe any serious obstetric
      complications. URS is a safe and reasonable treatment option for pregnant
      patients with ureteral stones refractory to medical treatment during pregnancy.

PMID- 23532422
TI  - Evaluation of acute renal colic: a comparison of non-contrast CT versus 3-T non
      contrast HASTE MR urography.
AB  - With the introduction of a 3-T scanner, magnetic resonance urography (MRU) may be
      an alternative imaging modality for evaluation of acute renal colic. We performed
      a prospective study to compare the performance of computed tomography (CT) with
      half-Fourier single shot turbo spin-echo (HASTE) MRU in the evaluation of
      patients with suspected renal colic. Patients presenting to the emergency
      department with acute renal colic were eligible for inclusion. Following a
      standard CT stone evaluation, patients underwent a non-contrast HASTE MRU study
      with a 3-T scanner. The presence of perinephric fluid, hydronephrosis, ureteral
      obstruction, and calculus was assessed. A total of 22 patients completed the
      study. Twenty (91 %) were diagnosed with an upper tract stone by radiographic
      findings. MRU detected a discrete stone in 50 % of the patients with stones
      detected by CT. Perinephric fluid was noted in 12 MRUs, compared to 7 CTs. Using
      CT as the reference standard, the combination of stone or perinephric fluid and
      ureteral dilation gave MRU a sensitivity of 84 %, specificity of 100 %, and
      accuracy of 86 % (95 % CI 0.72-1.0). HASTE MRU with a 3-T MR scanner can reliably
      detect the presence of upper urinary tract obstruction. Although CT imaging
      remains the superior modality with which to detect calculi, MRU detects a greater
      number of secondary signs of upper tract obstruction. For situations in which the
      use of ionizing radiation is undesirable, MRU is a reasonable imaging
      alternative.

PMID- 23532423
TI  - Association of calcium urolithiasis with urokinase P141L and 3'-UTR C>T
      polymorphisms in a Japanese population.
AB  - This was a case-control study to analyze the associations between calcium
      urolithiasis and the urokinase polymorphisms, P141L (rs2227564) and 3'-UTR C>T
      (rs4065), in a Japanese population. Cases consisted of 232 patients with urinary
      calcium stones (174 men and 58 women) who presented to a general hospital between
      April 2009 and June 2011. Among these cases, 115 (49.6 %) patients had calcium
      oxalate stones alone, and 113 (48.7 %) patients had calcium oxalate stones mixed
      with calcium phosphate stones. Controls consisted of 454 subjects who had a
      routine health check-up in the same prefecture. The two polymorphisms were
      genotyped via polymerase chain reaction with confronting two-pair primers. In the
      control group, the genotype frequencies of P141L were 0.573 for PP, 0.375 for PL,
      and 0.052 for LL, and those of 3'-UTR C>T were 0.835 for CC, 0.165 for CT, and TT
      was not identified. Neither of the polymorphisms was significantly associated
      with urolithiasis. The age- and sex-adjusted odds ratios of urolithiasis were
      0.96 [95 % confidence interval (CI), 0.66-1.41] for PL and 1.22 (0.58-2.57) for
      LL as compared with PP genotype of P141L, and 1.01 (0.62-1.64) for CT as compared
      with CC genotype of 3'-UTR C>T. When compared with the PP genotype of P141L, the
      frequency of PL was significantly lower in female cases with a family history of
      urolithiasis than in females without such family history (p = 0.028). P141L and
      3'-UTR polymorphisms of the urokinase gene are not associated with urolithiasis
      in a Japanese population.

PMID- 23532424
TI  - The feasibility of regional anesthesia in the percutaneous nephrolithotomy with
      supracostal approach and its comparison with general anesthesia.
AB  - There are various approaches for the percutaneous nephrolithotomy (PCNL).
      Supracostal approach is a well known technique for doing of it. This approach is
      being done commonly under general anesthesia (GA). In this retrospective study,
      we evaluated the feasibility of supracostal PCNL under regional anesthesia (RA)
      and compared it with the same procedure under GA. Since March 2000 to March 2005,
      a total of 123 renal stone cases underwent PCNL with supracostal access in our
      center. GA was selected in 69 cases (56 %) (Group 1), spinal anesthesia (SA) in
      45 cases (36.5 %), and epidural anesthesia (EA) in 9 cases (7.5 %) (Group 2). The
      operative time, success rate, hospital stay, and ensuing complications were
      compared between group 1 and group 2. There were no significant differences
      between groups 1 and 2 among surgical parameters, including age, stone area,
      anesthesia time, and hospitalization time (P > 0.05). There was no difference in
      the rate of complications or success rate between GA and RA cases (P > 0.05).
      Overall complete stone free rate, regardless of stone size, in relation to type
      of anesthesia was as follows: 88.4 % for GA, 88.9 % for EA, and 91.1 % for SA (P
      > 0.05). Conversion to GA was not needed in any patient with RA. The results
      showed that the supracostal PCNL with regional anesthesia was feasible but
      without evident advantages versus general anesthesia in this population, and
      possible advantages of the procedure in patients with pulmonary co-morbidities
      have still to be evaluated. The anesthesia related complications of RA were
      negligible and easily controllable.

PMID- 23532425
TI  - Percutaneous nephrolithotomy in patients with scoliosis: our institutional
      experience.
AB  - It is challenging to treat renal stones in patients with scoliosis. The present
      study was designed to study the safety and efficacy of minimally invasive
      percutaneous nephrolithotomy (mPCNL, 18 Fr) and standard tract PCNL (24 Fr) in
      patients with scoliosis. Twenty cases treated with mPCNL and 18 cases with
      standard tract PCNL were included in the present study. Laboratory data included
      preoperative routine complete blood count, serum creatinine, urine bacterial
      culture, etc. KUB, intravenous urography or CT scanning was done. Fifteen had
      lumbar and 23 had thoracolumbar scoliosis. Pulmonary function test was performed
      in all cases. Demographic and clinical details, operative characteristics and
      complications were studied and compared between two groups retrospectively. The
      stone burdens of two groups were averagely 754.4 and 816.2 mm(2), respectively (P
      = 0.194). Pulmonary function test indicated that 18 (47 %) out of 38 patients had
      decreased function for surgery and anesthesia. The stone clearance rates were 55
      and 67 %, respectively, after the first session (P = 0.522). The requirements of
      auxiliary treatments including second-look PCNL procedure or SWL (shock wave
      lithotripsy) were not significantly different for both groups. All patients from
      both groups achieved final stone clearance after auxiliary treatments.
      Complications of urinary collecting system injury or fever were observed in one
      and two cases in each group, respectively, (P = 0.548). There were no injuries to
      neighboring organs or pneumothorax. The requirement of blood transfusion for four
      cases in mPCNL group and three cases in the standard tract PCNL group,
      respectively, indicated no significant difference between two groups (P = 0.999).
      We are able to successfully and safely perform both mPCNL and standard tract PCNL
      in patients with scoliosis in our hospital. Compared with mPCNL, standard tract
      PCNL is even more efficient due to its shorter operative time.

PMID- 23532426
TI  - Time-dependent oxidative stress effects of percutaneous nephrolithotomy.
AB  - Aim of this study was to investigate the effects of operation time of
      percutaneous nephrolithotomy (PCNL) on renal function and hemodynamic response.
      Thirty-four patients (14 male, 20 female) with normal renal function who
      underwent unilateral single-tract PCNL between December 2010 and June 2011 were
      included in the study. The age, sex, stone size, grade of hydronephrosis,
      operative time, access pole, shock number of lithotripter, complications, stone
      free rate, and hemodynamic parameters during operation were recorded. Total blood
      count and oxidative stress parameters such as paraoxonase 1 (PON1), total
      antioxidant status (TAS), total oxidant status (TOS), and malonyldialdehyde (MDA)
      levels were examined before the operation as baseline levels and then at 30, 60,
      90, and 120 min during the operation. The mean age of the patients was 31.4 +/-
      18.8 (9-66 years) years. Mean stone size was 35.5 +/- 15.6 mm. Mean serum BUN and
      creatinine did not change postoperatively (p > 0.05), whereas mean WBC and 24-h
      urine cortisol were positively and hematocrite were negatively changed
      significantly (p < 0.05). Oxidative stress parameters such as PON1 and TAS showed
      statistically significant decreases, while TOS and MDA showed statistically
      significant increases with increased operation time, especially after 1 h (p <
      0.005). A bivariate correlation test showed correlation between oxidative stress
      parameters and operation time (p = 0.002), but no correlation was found between
      oxidative stress parameters and other parameters (p > 0.05). Oxidative stress and
      response to it increased with increasing operative time during a PCNL procedure,
      especially after 1 h. Further studies with a larger and longer series should be
      performed to clarify this issue further.

PMID- 23532427
TI  - RIRS versus mPCNL for single renal stone of 2-3 cm: clinical outcome and cost
      effective analysis in Chinese medical setting.
AB  - The aim of the study was to compare the clinical outcome and the cost
      effectiveness between retrograde intra renal surgery (RIRS) and mini-percutaneous
      nephrolithotripsy (mPCNL) for the management of single renal stone of 2-3 cm in
      Chinese medical setting. From May 2005 to February 2011, 115 patients with
      solitary renal calculi were treated either by RIRS or mPCNL. 56 patients were in
      RIRS group while 59 were in mPCNL group. Patients' demographics between the two
      groups, in terms of gender, age, BMI, history of ESWL as well as stone side,
      stone location and stone size were comparable. Peri-operative course, clinical
      outcome, complication rates and medical cost were compared. The effective
      quotient (EQ) of two groups was calculated. Data were analyzed using Fisher's
      exact test, Chi-square test and Student's t test. EQ for RIRS and mPCNL were 0.52
      and 0.90. The initial stone-free rate (SFR) of RIRS group and mPCNL group was
      71.4 and 96.6 %, respectively (P = 0.000). The mean procedure number was 1.18 in
      RIRS group and 1.03 in mPCNL group, respectively (P = 0.035). The operative time
      for RIRS was longer (P = 0.000) while the mean hospital stay was shorter (P =
      0.000). There was no statistical difference in peri-operative complications
      between the groups. The initial hospitalization cost, laboratory and radiology
      test cost of RIRS group were lower (P = 0.000). However, counting the retreatment
      cost in the two groups, the total medical expenditure including the overall
      hospitalization cost, overall laboratory and radiology test cost and post
      operative out-patient department (OPD) visit cost was similar between two groups.
      In conclusion, with similar total medical cost, mPCNL achieved faster stone
      clearance and lower retreatment rate without major complications, which implied
      higher cost-effectiveness for the treatment of single renal stone of 2-3 cm in
      Chinese medical setting. RIRS is also a safe and reliable choice for patients
      having contraindications or preference against mPCNL.

PMID- 23532428
TI  - Retrograde intrarenal surgery in patients with horseshoe kidneys.
AB  - Retrograde intrarenal surgery (RIRS) in patients with horseshoe kidneys (HSKs)
      remains poorly studied. The present study aimed to assess clinical success and
      stone-free rates in HSK patients with renal stones treated with flexible
      ureteroscopy. RIRS was attempted in 20 patients with 25 renal stones in HSK from
      December 2008 to January 2012. The patients were evaluated with imaging studies
      including plain abdominal radiography, intravenous urogram, abdominal
      ultrasonography or non-contrast tomography scan. Success rate was defined as
      stone-free or residual fragment less than 4 mm. Pre-operative, operative and
      postoperative data were retrospectively analyzed. A total of 20 patients were
      included in the present study (12 males, 8 females). 9 of 25 renal stones (36 %)
      were located in the lower calyx of the kidney, whereas 7 (28 %) in the middle
      calyx, 5 (20 %) in the renal pelvis and 4 (16 %) in the upper calyx. The mean
      stone size was 17.8 +/- 4.5 mm. The stone-free rate was 70 % after a single
      procedure. 6 patients required shock wave lithotripsy and two of these were
      completely stone-free. Average hospital stay was 1.4 +/- 0.7 days. Minor
      complications as classified by Clavien I or II occurred in 25 %. No major
      complications (Clavien III-V) occurred in the study group. RIRS is an effective
      and safe treatment modality for renal stones in patients with HSK. The procedure
      has minimal morbidity and high success rate.

PMID- 23532429
TI  - A huge bladder calculus causing acute renal failure.
AB  - A 81-year-old male was referred to our emergency outpatient unit due to acute
      renal failure. The level of serum creatinine was 276 MUmol/l. A CT scan showed
      bilateral hydronephroureter, large bladder stone (7 cm * 6 cm * 6 cm) and bladder
      wall thickness. He was diagnosed as post renal failure due to bilateral
      hydronephroureter. Large bladder stone is thought to be the cause of bilateral
      hydronephroureter and renal failure. To improve renal failure, we performed open
      cystolithotomy and urethral catheterization. Three days after the surgery, the
      level of serum creatinine decreased to 224 MUmol/l. He was discharged from our
      hospital with uneventful course. Bladder calculus is thought to be a rare cause
      of renal failure. We summarize the characteristics of bladder calculus causing
      renal failure. We should keep that long-term pyuria and urinary symptom, and
      repeated urinary tract infection can cause huge bladder calculus and renal
      failure in mind.

PMID- 23532430
TI  - Wrong perspective obscures the adverse effects of shock-wave lithotripsy.

PMID- 23532431
TI  - Age-specific prevalence of kidney stones in Chinese urban inhabitants.
AB  - The data on prevalence of kidney stones are lacking in China. We enrolled a total
      of 1,169,651 urban inhabitants across China in 2008 to detect if they are
      experiencing kidney stones by ultrasound diagnosis. Calibrated after the Chinese
      population census, the overall prevalence rate was estimated to be 4.0 %, 4.8 %
      in men and 3.0 % in women. A male predominance was found in all age group . The
      prevalence in the north (4.1 %) was slightly higher than that in the south (4.0
      %). This study provides a quantitative and updated estimate of the kidney stone
      prevalence in a nationally representative sample.

PMID- 23532432
TI  - Bacterial sepsis after extracorporeal shock-wave lithotripsy (ESWL) of calyceal
      diverticular stone.
AB  - Most calyceal diverticula are asymptomatic but symptoms occur when there is
      urinary stasis leading to infection and calculi. Septic shock after ESWL of
      calyceal stone occurs rarely. A 24-year-old woman had septic shock due to after
      extracorporeal shock-wave lithotripsy (ESWL) of asymptomatic calyceal
      diverticular stone.

PMID- 23532433
TI  - Pain and discomfort in closure of femoral access coronary angiography. The
      CLOSuredEvices Used in everyday Practice (CLOSE-UP) pain sub study.
AB  - BACKGROUND: Pain and discomfort in relation to vascular closure are the
      predominant patient complaints after coronary angiography (CAG). No large-scale
      randomized studies have evaluated pain and discomfort after CAG with access site
      closure by manual compression versus a vascular closure device (VCD). AIM: To
      compare pain and discomfort after femoral artery closure by manual compression
      versus FemoSeal(r) VCD. METHODS: The study is a sub study to the CLOSE-UP study,
      a randomized, single centre comparison of FemoSeal((r)) VCD versus manual
      compression after CAG. Pain and discomfort score was assessed immediately after
      the closure procedure, at time for mobilization, at discharge and after 14 days.
      RESULTS: 1014 patients were included and 1001 patients entered analysis. In
      hospital follow-up was obtained for all patients and 14-day follow-up was
      completed for 96% of patients. The closure procedure lasted 1 (1-1) min in the
      FemoSeal((r))VCD group and 8 (6-10) min in the manual compression group. Pain and
      discomfort score at the procedure was significantly higher in the
      FemoSeal((r))VCD group. No differences in pain and discomfort were detected after
      leaving the catheterization laboratory. CONCLUSION: Closure of femoral access
      after CAG by the FemoSeal((r))VCD was associated with significantly more pain and
      discomfort compared with closure by manual compression. No difference in pain and
      discomfort was found at follow-up.

PMID- 23532434
TI  - Steps toward developing an EEG biofeedback treatment for chronic pain.
AB  - Chronic pain, usually refractory to analgesics, is a significant problem for many
      individuals with spinal cord injury (SCI). Preliminary studies suggest that
      electroencephalography (EEG) biofeedback (also known as neurofeedback, NF) has
      the potential to help patients with otherwise refractory chronic pain. However,
      there remain many unanswered questions about the effects and mechanisms of this
      treatment. We studied 13 individuals with SCI and chronic pain with NF. Ten of
      the 13 individuals completed 4 sessions each of three different neurofeedback
      protocols assigned in random order for a total of 12 NF sessions. All three
      protocols had similar immediate effects on pain intensity. In addition, the
      participants reported modest pre- to post-treatment decreases in worst pain and
      pain unpleasantness following completion of the 12 NF sessions. These
      improvements were maintained at 3-month follow-up. The majority of the
      participants felt they benefited from and were satisfied with the treatment. No
      significant effects on measures of other outcome domains (sleep quality, pain
      interference and fatigue) were observed, although there was a non-significant
      trend for an increase in fatigue. Finally, pre- to post-treatment changes in EEG
      bandwidth activity, consistent with the training protocols, were observed in
      theta and alpha but not beta frequencies. The findings provide preliminary
      support for the potential efficacy of NF for the treatment of SCI-related pain,
      and suggest that further clinical studies are warranted.

PMID- 23532435
TI  - Hierarchical metallic and ceramic nanostructures from laser interference ablation
      and block copolymer phase separation.
AB  - We report on the formation of hierarchical nanostructures of Au, PtOx, FexOy and
      PdOx using a hybrid technique by combining laser interference ablation (LIA) and
      block copolymer phase separation (BCPS). Different types of hierarchical arrays
      can be obtained including square, triangular, linear and circular arrays by
      varying the loading time of the block co-polymer with metallic salts, and the
      laser interference technique. The primary ordering of the as-generated nanoarrays
      (30-100 nm) is tunable by changing either the composition of the block copolymer
      spun from solution or by changing other parameters that affect the phase
      separation kinetics of the block copolymer, while the secondary ordering of the
      features can be tuned from 200 nm to 2 MUm, by changing the angle of convergence
      of the laser beams on the patterned substrate. Such a robust method can be
      applied to the fabrication of other metallic and ceramic materials including Ag,
      Co, and Ni (O) and has potential use in the large scale fabrication of
      hierarchical arrays of catalysts that can be used to grow germanium, silicon
      nanowires using the vapour-liquid-solid growth (VLS) technique. The as-generated
      arrays can also find use in optical as well as sensor applications for
      biodetection and biosensing.

PMID- 23532436
TI  - Transitory brain stem edema following successfully transvenous embolization of a
      posterior fossa arteriovenous malformation.

PMID- 23532437
TI  - A case of natalizumab-associated progressive multifocal leukoencephalopathy-role
      for advanced MRI?

PMID- 23532438
TI  - Advances in targeted therapies XIV.

PMID- 23532439
TI  - Biomarkers in psoriasis and psoriatic arthritis.
AB  - Psoriasis is a common immune-mediated disease of the skin, which associates in 20
      30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both
      conditions is not fully understood as it is the result of a complex interaction
      between genetic, environmental and immunological factors. At present there is no
      cure for psoriasis and there are no specific markers that can accurately predict
      disease progression and therapeutic response. Therefore, biomarkers for disease
      prognosis and response to treatment are urgently needed to help clinicians with
      objective indications to improve patient management and outcomes. Although many
      efforts have been made to identify psoriasis/PsA biomarkers none of them has yet
      been translated into routine clinical practice. In this review we summarise the
      different classes of possible biomarkers explored in psoriasis and PsA so far and
      discuss novel strategies for biomarker discovery.

PMID- 23532440
TI  - Janus kinase inhibitors in autoimmune diseases.
AB  - Biological therapies directed at proinflammatory cytokines have irrevocably
      changed the landscape of treatment of rheumatoid arthritis (RA) and other
      autoimmune diseases. With the advances in our knowledge in cytokine signalling,
      the question emerges whether targeting intracellular signalling might also be a
      safe and efficacious strategy. Janus kinases or Jaks are critical for a large
      family of cytokines and the first Jak inhibitors has been approved by the FDA. It
      is therefore timely to consider this new category of drugs and reflect on their
      potential roles, present and future, in the treatment of RA and related
      disorders.

PMID- 23532441
TI  - Updated consensus statement on biological agents for the treatment of rheumatic
      diseases, 2012.

PMID- 23532442
TI  - Documentation of off-label use of biologics in Rheumatoid Arthritis.

PMID- 23532443
TI  - A 3D porous metal-organic framework containing nanotubes based on multiple
      helices.
AB  - Combining Co2 clusters with mixed H2bpdc and H2bpz ligands creates an
      unprecedented 3-fold interpenetrated 5-connected porous framework, which
      possesses the fascinating double-walled nanotubes structure assembled from
      nonuple and triple helices, and exhibits gas sorption properties.

PMID- 23532444
TI  - Anxiety as a core aspect of schizophrenia.
AB  - The clinical relevance of anxiety disorders in schizophrenia has been neglected
      for a long time and has only recently become the subject of a systematic
      investigation, although its consequences may have a very negative impact on the
      outcome and considerably worsen the trajectory of the disease. This could be
      originally related to the hierarchical organization of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM) and to the lack of assessment
      instruments. In this article, we will review the most recent literature
      concerning two of the most impairing anxiety disorders in comorbidity with
      schizophrenia, such as panic disorder and social anxiety disorder, briefly
      analyze the role of anxiety in the prodromal phase of psychosis and provide
      suggestions for the clinical assessment.

PMID- 23532446
TI  - Transfer of highly porous nanoparticle layers to various substrates through
      mechanical compression.
AB  - A new two-step layer transfer process is introduced that is capable of
      fabricating mechanically stabilized highly porous nanoparticle layers on various
      substrates. In a first step titanium dioxide nanoparticles were synthesized with
      Flame-Spray-Pyrolysis and accumulated on a filter paper in the gas phase. In a
      second step this highly porous filter cake is subsequently transferred to a final
      substrate via low pressure lamination at room temperature. This leads to
      mechanical restructuring and stabilization of the porous layer. Pore size
      analysis indicates homogenization of the layers through rearrangement of the
      aggregates inside the layers that increases with applied pressure. Additionally,
      the Young's moduli of the layers were quantified through Colloidal-Probe
      Technique indentation measurements with an Atomic-Force-Microscope. The highest
      lamination pressure of 2.5 MPa resulted in triplication of the Young's modulus.
      The results show that our novel two-step layer transfer process leads to
      mechanically stabilized layers that preserve their high porosity. Through the
      decoupling of the high temperature nanoparticle synthesis and the final substrate
      the process also enables the possibility to apply temperature sensitive
      substrates such as polypropylene foil.

PMID- 23532445
TI  - In vitro read-through of phenylalanine hydroxylase (PAH) nonsense mutations using
      aminoglycosides: a potential therapy for phenylketonuria.
AB  - Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive inborn error of
      phenylalanine metabolism, predominantly caused by mutations in the phenylalanine
      hydroxylase (PAH) gene. Approximately 10% of patients carry a nonsense mutation,
      which results in an inactive or unstable truncated protein. In some genetic
      disorders, including cystic fibrosis and Duchenne muscular dystrophy, restoration
      of full-length protein has been achieved by aminoglycoside antibiotics, such as
      gentamicin and G-418 (Geneticin). More recently, nonsense read-through has been
      induced at greater rates using a non-aminoglycoside drug, PTC124 (Ataluren),
      which has the advantage of being non-toxic in contrast to the antibiotics. The
      efficacy of read-through induced by three compounds, aminoglycosides G418 and
      gentamicin, and PTC124 were evaluated for four nonsense mutations of PAH in an in
      vitro expression system in two mammalian cell lines (COS-7 and HEK293). The
      production of full-length PAH was investigated using western blotting and the
      functionality confirmed by enzyme activity. Gentamicin and G-418 induced read
      through of nonsense PAH mutations in HEK293 cells. The read-through product
      partially restored enzymatic activity, which was significantly less than that of
      wild-type, but comparable to a missense mutation of PAH associated with less
      severe forms of PKU. Treatment with PTC124 up to 100 MUM did not result in full
      length PAH polypeptide. Nonsense read-through drugs are a potential form of
      treatment for PKU, although the high dosage of aminoglycosides used is not
      appropriate in a clinical setting. In vitro studies with new non-toxic read
      through agents as well as in vivo studies would also be essential to determine
      the extent of read-through required to restore normal phenylalanine levels.

PMID- 23532447
TI  - Outcome of subvastus approach in elderly nonobese patients undergoing bilateral
      simultaneous total knee arthroplasty: A randomized controlled study.
AB  - BACKGROUND: Subvastus approach in total knee arthroplasty (TKA) spares the
      quadriceps and may assist in faster rehabilitation. The present randomised
      controlled study was conducted to determine if the subvastus approach results in
      early recovery, faster mobilization, shorter hospital stay, and improved
      function. MATERIALS AND METHODS: 100 patients undergoing simultaneous bilateral
      TKA were randomized into two groups: subvastus group and medial parapatellar
      group. The patients were assessed clinically using VAS, time to straight leg
      raise, ability to stand with walker, ability to use a commode chair, ability to
      climb stairs, flexion at discharge, and day of discharge. Perioperative blood
      loss and duration of surgery were also compared. The patient were kept on same
      pain management and physiotherapy protocol. The evaluation was done at day 0,1,3
      and at discharge. Statistical analyses tested the null hypotheses of no
      differences in patients treated with either group at 95% significance level (P <
      0.05). RESULTS: The VAS score was significantly lower in subvastus group on day 1
      and day 3. Also mean hospital stay was 2.04 days less in subvastus group.
      Patients with subvastus approach were able to perform straight leg raising 0.44
      days earlier. Though time to stand with walker was same for both groups, the
      ability to use commode chair, and climb stairs was significantly early (P < 0.05)
      in the subvastus group. The average flexion at the time of discharge in subvastus
      and parapatellar group were 100.8 and 96.8 degrees , respectively. The mean
      perioperative blood loss in subvastus group and parapatellar group were 343 ml
      and 372 ml, respectively. Average surgical time required for subvastus approach
      and parapatellar approach were 108.5 and 94.3 min, respectively. CONCLUSIONS:
      Subvastus approach produce appreciably less pain and faster mobilization due to
      lesser insult to quadriceps, thus assisting in early rehabilitation, shorter
      hospital stay, less expenditure, and more patient satisfaction.

PMID- 23532448
TI  - Contemporary effective population and metapopulation size (N e and meta-N e):
      comparison among three salmonids inhabiting a fragmented system and differing in
      gene flow and its asymmetries.
AB  - We estimated local and metapopulation effective sizes ([Formula: see text] and
      meta-[Formula: see text]) for three coexisting salmonid species (Salmo salar,
      Salvelinus fontinalis, Salvelinus alpinus) inhabiting a freshwater system
      comprising seven interconnected lakes. First, we hypothesized that [Formula: see
      text] might be inversely related to within-species population divergence as
      reported in an earlier study (i.e., FST: S. salar> S. fontinalis> S. alpinus).
      Using the approximate Bayesian computation method implemented in ONeSAMP, we
      found significant differences in [Formula: see text] ([Formula: see text])
      between species, consistent with a hierarchy of adult population sizes ([Formula:
      see text]). Using another method based on a measure of linkage disequilibrium
      (LDNE: [Formula: see text]), we found more finite [Formula: see text] values for
      S. salar than for the other two salmonids, in line with the results above that
      indicate that S. salar exhibits the lowest [Formula: see text] among the three
      species. Considering subpopulations as open to migration (i.e., removing putative
      immigrants) led to only marginal and non-significant changes in [Formula: see
      text], suggesting that migration may be at equilibrium between genetically
      similar sources. Second, we hypothesized that meta-[Formula: see text] might be
      significantly smaller than the sum of local [Formula: see text]s (null model) if
      gene flow is asymmetric, varies among subpopulations, and is driven by common
      landscape features such as waterfalls. One 'bottom-up' or numerical approach that
      explicitly incorporates variable and asymmetric migration rates showed this very
      pattern, while a number of analytical models provided meta-[Formula: see text]
      estimates that were not significantly different from the null model or from each
      other. Our study of three species inhabiting a shared environment highlights the
      importance and utility of differentiating species-specific and landscape effects,
      not only on dispersal but also in the demography of wild populations as assessed
      through local [Formula: see text]s and meta-[Formula: see text]s and their
      relevance in ecology, evolution and conservation.

PMID- 23532449
TI  - Limbic system associated membrane protein as a potential target for
      neuropsychiatric disorders.
AB  - The studies performed in laboratory animals and psychiatric patients suggest a
      possible role of limbic system-associated membrane protein (LAMP) in the
      mechanisms of psychiatric disorders. Stressful manipulations and genetic
      invalidation have revealed a role of the Lsamp gene in the regulation of anxiety
      in rodents. Besides that, Lsamp-deficient mice display reduced aggressiveness and
      impaired adaptation in novel and stressful environments. The behavioral effects
      of amphetamine were blunted in genetically modified mice. Recent pharmacological
      and biochemical studies point toward altered function of GABA-, 5
      hydroxytryptamine-, and dopaminergic systems in Lsamp-deficient mice. Moreover,
      we found an association between the gene polymorphisms of LSAMP and major
      depressive disorder (MDD). Patients suffering from MDD had significantly
      increased ratio between risk and protective haplotypes of the LSAMP gene compared
      to healthy volunteers. However, the impact of these haplotypes for the function
      of LAMP is not clear and remains to be elucidated in future studies.

PMID- 23532450
TI  - Distribution of Subsidized Insecticide-treated Bed Nets through a Community
      Health Committee in Boboye Health District, Niger.
AB  - In Niger, insecticide-treated bed nets (ITNs) have been distributed to the target
      group of households with young children and/or pregnant women at healthcare
      facilities in the course of antenatal/immunization clinics. With the aim of
      universal coverage, ITNs were additionally distributed to households through
      strengthened community health committees in 2009. This study assessed the impact
      of the community-based net distribution strategy involving community health
      committees in the ITN coverage in Boboye Health District, Niger. A cross
      sectional survey was carried out on 1,034 households drawn from the intervention
      area (the co-existence of the community-based system together with the facility
      based system) and the control area (the facility-based system alone). In the
      intervention area, 55.8% of households owned ITNs delivered through the community
      based system, and 29.6% of households exclusively owned ITNs obtained through the
      community-based system. The community-based system not only reached households
      within the target group (54.6% ownership) but also those without (59.1%
      ownership). Overall, household ITN ownership was significantly higher in the
      intervention area than in the control area (82.5% vs. 60.7%). In combination, the
      community-based system and the facility-based system achieved a high ITN
      coverage. The community-based system contributed to reducing leakage in the
      facility-based system.

PMID- 23532451
TI  - Fluoride bioaccumulation and toxic effects on the survival and behavior of the
      endangered white-clawed crayfish Austropotamobius pallipes (Lereboullet).
AB  - Laboratory experiments were performed to examine the toxic effects of fluoride
      (F(-)) on the survival and behavior of white-clawed crayfish (Austropotamobius
      pallipes). Body fluoride contents (bioaccumulation) of test crayfish were also
      examined. No significant differences between male and female crayfish regarding
      mortality, escape (tail-flip) response, and fluoride bioaccumulation were
      detected. For mortality, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h median lethal
      concentrations (LC50) were estimated to be 93.0, 55.3, 42.7, 36.5, 32.9, 30.6,
      and 28.9 mg F(-)/l, respectively. For the escape response, 48-, 72-, 96-, 120-,
      144-, 168- and 192-h median effective concentrations (EC50) were estimated to be
      18.4, 11.1, 8.6, 7.4, 6.7, 6.2 and 5.9 mg F(-)/l, respectively. Average food
      consumption in test crayfish tended to decrease with increasing water fluoride
      concentration with a 192-h lowest-observed effect concentration of 10.7 mg F(
      )/l. These results indicate that the escape response was the most sensitive end
      point to fluoride toxicity followed by food consumption and mortality. Fluoride
      bioaccumulation in test crayfish increased with increasing water fluoride
      concentration and exposure time. The exoskeleton accumulated more fluoride than
      muscle. A comparison of the obtained results with previous data for other
      freshwater invertebrates shows that white-clawed crayfish are relatively tolerant
      to fluoride toxicity. We conclude that fluoride pollution in freshwater
      ecosystems should not be viewed as an important risk factor contributing to the
      catastrophic decrease of A. pallipes in many European countries. Our results
      indicate that fluoride bioaccumulation in A. pallipes might be used as a
      bioindicator of fluoride pollution in freshwater ecosystems where it is present.

PMID- 23532452
TI  - Is virtual reality training for resident cataract surgeons cost effective?

PMID- 23532453
TI  - Comparative measurement of intraocular pressure by Icare tonometry and Airpuff
      tonometry in healthy subjects and patients wearing therapeutic soft contact
      lenses.
AB  - BACKGROUND: The aim of the present study was to compare the measurement of
      intraocular pressure (IOP) through a therapeutic soft contact lens with the
      "native" measurement. We additionally investigate whether a rebound tonometer
      (RT) or non-contact tonometer (NCT) is more suitable to measure IOP through a
      bandage contact lens. METHODS: The IOP was determined using each of the two
      methods, three times successively with (lens measurement) and without (native
      measurement) a soft contact lens. The Icare tonometer (Icare(r) TA01i, Icare
      Finland Oy, 23 subjects) and the Airpuff tonometer (Nidek NT 53OP, Nidek CO.,
      LTD, Hiroishi Gamagori, Aichi, Japan, 16 subjects) were used. We compared the
      mean values (validity parameter) and standard deviation (precision parameter) of
      the three individual measurements in each case using the paired t-test. In
      addition, we conducted a power analysis to estimate the maximum error in the
      measurement caused by the contact lens (power level set to 0.8). RESULTS: With
      the Airpuff tonometer we detected no statistically significant between the lens
      and the native measurement (15.6 +/- 2.6 vs. 15.3 +/- 2.6 mmHg; p = 0.42). The
      power analysis revealed that the maximum error caused by the contact lens was 1.2
      mmHg. The Icare tonometry, however, trended toward higher values in the contact
      lens measurements (17.5 +/- 4.3 vs. 16.4 +/- 3.5 mmHg in the native measurements;
      p = 0.05). Interestingly, this difference exhibited a statistically significant
      correlation with the corneal thickness (0.03 mmHg per MUm corneal thickness; p =
      0.04). CONCLUSION: The use of NCT and RT for IOP measurement over a soft contact
      lens is feasible. The accuracy appears to be sufficient for the most common
      clinical applications.

PMID- 23532454
TI  - Choroidal assessment in idiopathic panuveitis using optical coherence tomography.
AB  - BACKGROUND: Idiopathic panuveitis is a diagnosis of exclusion that lacks
      distinguishing features on fluorescein and indocyanine green angiography.
      Choroidal hypoperfusion or ischaemia has been implicated in panuveitis of
      different aetiologies. In this study, we use enhanced depth imaging optical
      coherence tomography (OCT) to examine the choroid and its vasculature in patients
      with this disease. METHODS: In this retrospective, cross-sectional study, OCT
      derived measurements of retinal and choroidal thickness were obtained after
      manual segmentation using custom software. Choroidal measurements were further
      subdivided into Haller's large vessel layer (HLVL) and Sattler's medium vessel
      layer (SMVL), and correlated with clinical parameters. RESULTS: Twenty-one eyes
      from 21 patients were included. A reduction in hypo-reflective spaces,
      corresponding to vascular lumens, was observed in HLVL. The mean thickness of
      both the choroid (233.7 +/- 73.3 MUm), and HLVL (167.8 +/- 53.7 MUm), was less
      than that previously reported for normal eyes. Choroidal thickness expressed as a
      ratio to retina thickness showed significant correlation to visual acuity (r =
      0.58, p = 0.006). This correlation was maintained in the ratio between HLVL and
      retinal thickness (r = 0.56, p = 0.009), but not in SMVL to retinal thickness (r
      = 0.352, p = 0.12). CONCLUSIONS: This study reports novel OCT-derived parameters
      in patients with idiopathic panuveitis. We noted loss of hyporeflectivity in
      HLVL, and thinning of both HLVL and the choroid as a whole. The observed
      correlation between visual acuity and the ratio of choroidal to retinal thickness
      is a strong enhanced depth imaging (EDI)-OCT derived candidate for prospective
      validation in future studies.

PMID- 23532455
TI  - The need in dural graft suturing in Chiari I malformation decompression: A
      prospective, single-blind, randomized trial comparing sutured and sutureless
      duraplasty materials.
AB  - BACKGROUND: This study compared the use of two commonly utilized dural closure
      techniques used in augmentation duraplasty for Chiari malformation I (CM I) and
      evaluated their efficacy and outcome in terms of quality of life assessments.
      METHODS: This prospective randomized study compared sutureless (DuraGen) and
      suturable (Dura-Guard) techniques in CM I decompression. Clinical parameters,
      cost analysis, and SF-36 Quality of Life Questionnaire (QLQ) were utilized to
      assess outcome. RESULTS: Thirty-four patients were enrolled. Average age was 38.7
      +/- 12.2 years (mean +/- SD (Standard Deviation)) and 82% of patients were
      female. Sixteen patients received DuraGen and 18 Dura-Guard. Age and gender were
      similar among groups. Postoperative complications did not differ between groups.
      Operative cost and time were less for DuraGen, whereas hospital stay was less
      with Dura-Guard, neither was statistically significant. Average QLQ scores at
      months 1, 2, and 3 improved in both groups. Dura-Guard patients showed greater
      improvement in quality of life at month 2 (P < 0.05) but groups did not differ at
      final survey. All patient's physical health (P < 0.005) and function (P < 0.005)
      were significantly improved. Outcome did not differ between groups and all
      patients showed significant improvement (P < 0.05). CONCLUSION: Both techniques
      are effective in reaching the goals of decompressive surgery for CM I and did not
      differ in quality of life at final survey. All patients showed significant
      improvement in physical function, physical health, and outcome following surgery.
      With all variables being equal the choice of duraplasty material may be based
      upon surgeon's preference.

PMID- 23532456
TI  - Mexican Pharmacies and Antibiotic Consumption at the US-Mexico Border.
AB  - OBJECTIVE: To study antibiotic dispensing to US and Mexican residents, at Mexican
      pharmacies at the US-Mexico border, and the pharmacy clerks' capability to
      promote appropriate use. METHODS: The site selected was Ciudad Juarez, Chihuahua
      (pop. 1.2 million) separated from El Paso, Texas (pop. 800,000) by the Rio Grande
      River. A convenience sample of 32 pharmacies located near the international
      bridges, major shopping centers, and interior neighborhoods was selected.
      Pharmacy clients were interviewed (n=230) and 152 interactions between clients
      and pharmacy clerks were observed. Information was obtained about education and
      pharmaceutical training of 113 clerks working in 25 pharmacies. A senior pharmacy
      clerk in each of the 25 pharmacies was interviewed and asked for their
      recommendations to clients presenting two clinical scenarios and seven diagnoses.
      FINDINGS: Professionally trained pharmacists only spend a few hours a week in
      some pharmacies. Clerks' education levels are very low; some have only completed
      primary education. There is no required pharmaceutical training and their
      knowledge about pharmaceuticals comes mostly from representatives of the
      pharmaceutical industry. Clerks' knowledge of antibiotics, the most frequently
      sold class of medicines (65% without prescription), is very limited. Clients
      trust pharmacy clerks and tend to follow their advice. CONCLUSIONS: The findings
      raise concerns about dispensing of antibiotics at Mexican border pharmacies and
      antibiotic overuse due to lack of control. Because inappropriate antibiotic use
      contributes to increased resistance, pharmacy clerks should receive independent
      training to dispense antibiotics and promote their appropriate use.

PMID- 23532457
TI  - A systematic investigation of the invariance of resting-state network patterns:
      is resting-state fMRI ready for pre-surgical planning?
AB  - OBJECTIVES: Measurements of resting-state networks (RSNs) have been used to
      investigate a wide range of diseases, such as dementia or epilepsy. This raises
      the question whether this method could also serve as a pre-surgical planning
      tool. Generating reliable functional connectivity patterns is of crucial
      importance, particularly for pre-surgical planning, as these patterns may
      directly affect the outcome. METHODS: This study investigated the reproducibility
      of four commonly used resting-state conditions: fixation of a black crosshair on
      a white screen; fixation of the center of a black screen; eyes-closed and
      fixation of the words "Entspann dich!" (Engl., "relax"). Ten healthy, right
      handed male subjects (mean age, 25 years; SD 2) participated in the experiment.
      The spatial overlap for different RSNs across the four conditions was calculated.
      RESULTS: The spatial overlap across all four conditions was calculated for each
      seed region on a single subject and at the group level. Activation maps at the
      single-subject and group levels were highly stable, especially for the reading
      network (RNW). The lowest consistency measures were found for the visual network
      (VIN). At the single-subject level spatial overlap values ranged from 0.31 (VIN)
      to 0.45 (RNW). CONCLUSION: These findings suggest that RSN measurements are a
      reliable tool to assess language-related networks in clinical settings.
      Generally, resting-state conditions showed comparable activation patterns,
      therefore no specific conditions appears to be preferable.

PMID- 23532458
TI  - Homoeologous GSL-ELONG gene replacement for manipulation of aliphatic
      glucosinolates in Brassica rapa L. by marker assisted selection.
AB  - Aliphatic glucosinolates are the predominant sulfur-rich plant secondary
      metabolites in economically important Brassica crops. Glucosinolates and their
      hydrolysis products are involved in plant-microbe, plant-insect, plant-animal,
      and plant-human interactions. It is, therefore, important to manipulate
      glucosinolate profiles and contents in Brassica species. In this study, aliphatic
      glucosinolates were genetically manipulated through homoeologous recombination in
      backcross lines followed by marker assisted selection in B. rapa. A resynthesized
      B. napus line, from a cross between B. rapa and B. oleracea, was backcrossed with
      Chinese cabbage doubled haploid line, RI16. Marker assisted selection for non
      functional gene was performed in each backcross generations. Advanced backcross
      progenies (BC3F2) were developed to identify homoeologous gene replacement and/or
      introgression. Reduction in 5C aliphatic glucosinolates (gluconapoleiferin,
      glucoalyssin, and glucobrassicanapin) was observed in BC3F2 progenies of the
      recurrent parent that carried the GSL-ELONG (-) gene. The GSL-ELONG (-) positive
      backcross progenies were also screened by the A-genome and BraGSL-ELONG gene
      specific marker, which linked with 5C aliphatic glucosinolates. The A-genome
      specific marker was absent in the plants of advanced backcross progenies which
      showed reduction in 5C aliphatic glucosinolates. The results suggest that the
      functional allele had been replaced by the non-functional GSL-ELONG (-) allele
      from B. oleracea. Some advanced backcross progenies (BC3F2) positive for the GSL
      ELONG (-) allele and the A-genome specific SCAR marker BraMAM1-1 did not show
      reduction in 5C aliphatic glucosinolates, suggesting that GSL-ELONG (-) allele is
      recessive. Replacement of the functional locus in the A-genome by non-functional
      counterpart in the C-genome reduced the content of 5C aliphatic glucosinolates in
      B. rapa seeds with 20 MUmol/g.

PMID- 23532459
TI  - DFT studies of imino and thiocarbonyl ligands with the pentaaqua Mg2+ cation:
      affinity and associated parameters.
AB  - The affinity of the pentaaqua Mg(2+) cation for a set of para-substituted imino
      [HN = CHC6H4(R)] and thiocarbonyl [S = CHC6H4(R)] ligands (R = H, F, Cl, Br, OH,
      OCH3, CH3, CN, NH2 and NO2) was analyzed with DFT (B3LYP/6-31+G(d)) and semi
      empirical (PM6-DH2) methods. The interaction enthalpy was calculated to quantify
      the affinity of the Mg(2+) cation for the ligands. Additionally, geometric and
      electronic parameters were correlated with the intensity of the metal-ligand
      interaction. The imino ligands have stronger interaction with the pentaaqua
      Mg(2+) cation than the thiocarbonyl derivatives. The electronic nature of the
      substituent is the main parameter that determines the interaction enthalpy.
      Ligands with electron donor substituents have more exothermic interaction
      enthalpies than those with electron withdrawing groups. The HSBA analysis showed
      that the interaction between the Mg(2+) cation and hard bases (imino ligands) is
      stronger than with soft bases (thiocarbonyl derivatives). The EDA analysis showed
      that the electrostatic, covalent and repulsion components of the interaction are
      the most affected by the substituent, whereas the dispersion and exchange
      components are almost constant.

PMID- 23532460
TI  - PML(NLS(-)) inhibits cell apoptosis and promotes proliferation in HL-60 cells.
AB  - Promyelocytic leukemia (PML) is a cell-growth suppressor, and PML-retinoic acid
      receptor alpha (PML-RARalpha) is known as a fusion gene of acute promyelocytic
      leukemia (APL). Studies have reported that neutrophil elastase(NE) cleaved bcr-1
      derived PML-RARalpha in early myeloid cells leading to the removal of nuclear
      localization signal (NLS) from PML. The resultant PML without NLS named PML(NLS(
      )). PML(NLS(-)) mainly locates and functions in the cytoplasm. PML(NLS(-)) may
      act in different ways from PML, but its biological characteristics have not been
      reported. In this study, the PML (NLS(-)) was silenced with shRNA [HL
      60/pPML(NLS(-))-shRNA] and over-expressed by preparation of recombinant
      adenovirus [HL-60/pAd-PML(NLS(-))]. The mRNA and protein expression of PML(NLS(
      )) were detected by RT-PCR and Western blot respectively. Cell proliferation in
      vitro was assessed by MTT assay. Flow cytometry (FCM) was used to detect
      apoptotic cells. The transcription of BCL-2, BAX and C-MYC was detected in HL
      60/pAd-PML(NLS(-)) cells. Our results showed that compared to the control group,
      the expression of PML(NLS(-)) was significantly reduced in the HL-60/pPML(NLS(-))
      shRNA cells, and increased significantly in the HL-60/pAd-PML(NLS(-)) cells. The
      proliferation was significantly inhibited in the HL-60/pPML(NLS(-))-shRNA cells
      in a time-dependent manner, but markedly promoted in the HL-60/pAd-PML(NLS(-))
      cells treated with 60 MUmol/L emodin. FCM revealed the apoptosis increased in HL
      60/pPML(NLS(-))-shRNA cells, and decreased in the HL-60/pAd-PML(NLS(-)) cells.
      The expression of BAX decreased significantly, while that of BCL-2 and C-MYC
      increased significantly in HL-60/ pAd-PML(NLS(-)) cells. Down-regulation of
      PML(NLS(-)) expression inhibits the proliferation and induces the apoptosis of HL
      60 cells. On the contrary, over-expression of PML(NLS(-)) promotes the
      proliferation and reduce the emodin-induced apoptosis of HL-60 cells.

PMID- 23532461
TI  - Increased alkalotolerant and thermostable ribonuclease (RNase) production from
      alkaliphilic Streptomyces sp. M49-1 by optimizing the growth conditions using
      response surface methodology.
AB  - Total of 171 alkaliphilic actinomycetes were evaluated for extracellular RNase
      production and Streptomyces sp. M49-1 was selected for further experiments.
      Fermentation optimization for RNase production was implemented in two steps using
      response surface methodology with central composite design. In the first step,
      the effect of independent fermentation variables including temperature, initial
      pH and process time were investigated. After identification of carbon and
      nitrogen sources affecting the production by one variable at a time method,
      concentrations of glucose and yeast extract and also inoculum size were chosen
      for the second central composite design. A maximum RNase activity was obtained
      under optimal conditions of 4.14 % glucose concentration, 4.63 % yeast extract
      concentration, 6.7 * 106 spores as inoculum size for 50 ml medium, 42.9  degrees
      C, 91.2 h process time and medium initial pH 9.0. Optimum activity of the enzyme
      is achieved at pH 11 and temperature 60  degrees C. The enzyme is highly stable
      at pH range 9.0-12.0 and at 90  degrees C after 2 h. Statistical optimization
      experiments provide 2.25 fold increases in the activity of alkalotolerant and
      thermostable RNase and shortened the fermentation time compared to that of
      unoptimized condition. The members of Streptomyces can be promising qualified
      RNase producer for pharmaceutical industries.

PMID- 23532462
TI  - Complex mullerian duct anomaly in a young female with primary amenorrhoea,
      infertility, and chronic pelvic pain.
AB  - Mullerian duct anomalies, though rare, can be a treatable cause of pelvic pain
      and infertility. Various complex Mullerian duct anomalies may exist with
      combination of features of more than one class. Since there are no precise
      clinical or imaging criteria to enable specific categorisation, there is
      ambiguous classification of these anomalies by various radiologists and
      clinicians. A young female presented with complaints of chronic pelvic pain,
      primary amenorrhoea and infertility. The patient was evaluated by sonography and
      Magnetic Resonance Imaging and diagnosed as case of complex mullerian duct
      anomaly, a unicornuate uterus with cervical dysgenesis and cavitated,
      noncommunicating, rudimentary right horn. The findings were confirmed on
      laprohysteroscopy and the patient underwent hystertectomy. There should be an
      integrated clinico-radiological classification scheme and familiarity with rare
      and complex anomalies for appropriate diagnosis and management of complex
      Mullerian duct anomalies.

PMID- 23532463
TI  - Anti-oxidation treatment of ultra high molecular weight polyethylene components
      to decrease periprosthetic osteolysis: evaluation of osteolytic and osteogenic
      properties of wear debris particles in a murine calvaria model.
AB  - Wear debris-induced osteolysis remains the greatest limitation of long-term
      success for total joint replacements with ultra-high molecular weight
      polyethylene (UHMWPE) bearings. To address oxidative degradation post-gamma
      irradiation, manufacturers are investigating the incorporation of antioxidants
      into PE resins. Similarly, larger molecular weight monomers have been developed
      to increase crosslinking and decrease wear debris, and ultimately osteolysis.
      However, the effects of modifying monomer size, crosslink density, and
      antioxidant incorporation on UHMWPE particle-induced osteoclastic bone resorption
      and coupled osteoblastic bone formation have never been tested. Here, we review
      the field of antioxidant-containing UHMWPE, and present an illustrative pilot
      study evaluating the osteolytic and osteogenic potential of wear debris generated
      from three chemically distinct particles (MARATHON(r), XLK, and AOXTM) as
      determined by a novel 3D micro-CT algorithm designed for the murine calvaria
      model. The results demonstrate an approach by which the potential osteoprotective
      effects of antioxidants in UHMWPE can be evaluated.

PMID- 23532464
TI  - A reliable statistical method to detect eyeblink-artefacts from
      electroencephalogram data only.
AB  - For data preprocessing and artefact removal in an ERP experiment we were
      confronted with the question how blink artefacts can be detected reliably, even
      in the absence of usable electrooculogram (EOG) data. We propose an objective and
      quantitative method for the automatic detection of eyeblink artefacts from raw
      data using extreme value statistics, with a p-value acting as a threshold
      parameter. For testing the method, we used 29 channel electroencephalogram
      recordings of 55 healthy subjects. A total 7,700 s of EEG were analysed. The
      proposed method was found to detect blink artefacts reliably, showing that
      extreme value statistics can be employed to detect blink artefacts, even in the
      absence of EOG recordings. 

PMID- 23532465
TI  - White matter integrity following traumatic brain injury: the association with
      severity of injury and cognitive functioning.
AB  - Traumatic brain injury (TBI) frequently results in impairments of memory, speed
      of information processing, and executive functions that may persist over many
      years. Diffuse axonal injury is one of the key pathologies following TBI, causing
      cognitive impairments due to the disruption of cortical white matter pathways.
      The current study examined the association between injury severity, cognition,
      and fractional anisotropy (FA) following TBI. Two diffusion tensor imaging
      techniques-region-of-interest tractography and tract-based spatial statistics
      were used to assess the FA of white matter tracts. This study examined the
      comparability of these two approaches as they relate to injury severity and
      cognitive performance. Sixty-eight participants with mild-to-severe TBI, and 25
      healthy controls, underwent diffusion tensor imaging analysis. A subsample of 36
      individuals with TBI also completed cognitive assessment. Results showed
      reduction in FA values for those with moderate and severe TBI, compared to
      controls and individuals with mild TBI. Although FA tended to be lower for
      individuals with mild TBI no significant differences were found compared to
      controls. Information processing speed and executive abilities were most strongly
      associated with the FA of white matter tracts. The results highlight similarities
      and differences between region-of-interest tractography and tract-based spatial
      statistics approaches, and suggest that they may be used together to explore
      pathology following TBI. 

PMID- 23532466
TI  - Food and Drug Administration (FDA) postmarket reported side effects and adverse
      events associated with pulmonary hypertension therapy in pediatric patients.
AB  - Because most medications for pediatric pulmonary hypertension (PH) are used off
      label and based on adult trials, little information is available on pediatric
      specific adverse events (AEs). Although drug manufacturers are required to submit
      postmarket AE reports to the Food and Drug Administration (FDA), this information
      is rarely transmitted to practitioners. In the setting of a recent FDA warning
      for sildenafil, the authors sought to give a better description of the AEs
      associated with current therapies in pediatric PH. In January 2010, a written
      request was made to the Food and Drug Administration for AE records of commonly
      used PH medications. Reports were screened for pediatric patients, analyzed in
      terms of AEs, and compared with the medical literature. Arbitrarily, AEs that
      could be attributed to concomitant medications were not attributed to the PH
      medication in question. Adverse events occurring in more than 5 % of events for
      each drug were assumed to be associated with the targeted PH medication. Between
      November 1997 and December 2009, 588 pediatric AE reports (death in 257 cases)
      were reported for the three most commonly used therapies: bosentan, epoprostenol,
      and sildenafil. Many of the AEs were similar to those reported previously.
      However, 27 AEs not previously reported in the literature (e.g., pulmonary
      hemorrhage, hemoptysis, and pneumonia) were found. The FDA postmarket records for
      PH medications in pediatric patients show a significant number of AEs. The
      discovery of AEs not previously reported will better inform those caring for
      these complex and critically ill children, and the large number of deaths suggest
      they may be underreported in current literature.

PMID- 23532467
TI  - Regional implementation of newborn screening for critical congenital heart
      disease screening in Abu Dhabi.
AB  - Congenital heart disease (CHD) is the most common birth defect and affects
      approximately 8 out of every 1,000 infants born each year. Despite antenatal
      screening and at least one examination before discharge infants with critical CHD
      (CCHD) are routinely not detected before discharge from the newborn nursery.
      Newborn screening for CCHD using pulse oximetry is widely endorsed however until
      recent efforts, CCHD screening programs had only been implemented at the
      individual hospital level. The purpose of this paper is to describe the
      implementation of CCHD screening across the entire Emirate of Abu Dhabi. The
      Health Authority-Abu Dhabi (HAAD), in collaboration with Children's National
      Medical Center (Children's National), successfully implemented CCHD screening at
      the emirate level using a "train-the-trainer," two-tiered approach, starting with
      two pilot hospitals then rolling the program out to all birthing facilities. In
      the first year, CCHD screening was added as a mandatory test to the HAAD Newborn
      Screening Standard, has been implemented in most birthing facilities, and occurs
      for the majority of infants (86 %) in Abu Dhabi. This led to the identification
      of ten newborns with CCHD. Based on the successful identification and mitigation
      of barriers to implementation, the approach may be adapted for similar programs
      in other populations.

PMID- 23532468
TI  - Nano-bio effects: interaction of nanomaterials with cells.
AB  - With the advancements in nanotechnology, studies on the synthesis, modification,
      application, and toxicology evaluation of nanomaterials are gaining increased
      attention. In particular, the applications of nanomaterials in biological systems
      are attracting considerable interest because of their unique, tunable, and
      versatile physicochemical properties. Artificially engineered nanomaterials can
      be well controlled for appropriate usage, and the tuned physicochemical
      properties directly influence the interactions between nanomaterials and cells.
      This review summarizes recently synthesized major nanomaterials that have
      potential biomedical applications. Focus is given on the interactions, including
      cellular uptake, intracellular trafficking, and toxic response, while changing
      the physicochemical properties of versatile materials. The importance of
      physicochemical properties such as the size, shape, and surface modifications of
      the nanomaterials in their biological effects is also highlighted in detail. The
      challenges of recent studies and future prospects are presented as well. This
      review benefits relatively new researchers in this area and gives them a
      systematic overview of nano-bio interaction, hopefully for further experimental
      design.

PMID- 23532469
TI  - Reduction of Blood Pressure by AT1 Receptor Decoy Peptides.
AB  - BACKGROUND: We previously identified the binding of the chaperone protein gamma
      aminobutyric acid receptor-associated protein (GABARAP) to a sequence on the
      carboxy-terminus of the angiotensin II AT1 receptor (AT1R) and showed that this
      binding enhances AT1R trafficking to the cell surface as well as angiotensin
      signaling. METHODS: In this study, we treated sodium-depleted mice with decoy
      peptides consisting either of a fusion of the cell-penetrating peptide penetratin
      and the GABARAP/AT1R binding sequence or penetratin fused to a mutated AT1R
      sequence. We used telemetry to measure blood pressure. RESULTS: Systolic and
      diastolic pressure fell during the 24 hours following decoy peptide injection but
      not after control peptide injection. Active cell-penetrating decoy peptide
      decreased 24-hour average systolic blood pressure from 129.8 +/- 4.7 mmHg to
      125.0 +/- 6.0 mmHg (mean +/- standard deviation). Diastolic blood pressure fell
      from 99.0 +/- 7.1 mmHg to 95.0 +/- 9.2 mmHg (n=5). Administration of the control
      peptide raised systolic blood pressure from 128.7 +/- 1.3 mmHg to 131.7 +/- 2.9
      mmHg and diastolic pressure from 93.9 +/- 4.5 mmHg to 95.9 +/- 4.2 mmHg (n=5).
      The decreases in both systolic and diastolic blood pressure after active peptide
      administration were statistically significant compared to control peptide
      administration (P<0.05, two-tailed Wilcoxon rank-sum test). CONCLUSION: These
      results indicate the physiological and potentially therapeutic relevance of
      inhibitors of GABARAP/AT1R binding.

PMID- 23532470
TI  - Clostridium difficile infection is associated with increased risk of death and
      prolonged hospitalization in children.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is associated with significant
      morbidity and mortality among adults. However, outcomes are poorly defined among
      children. METHODS: A retrospective cohort study was performed among hospitalized
      children at 41 children's hospitals between January 2006 and August 2011.
      Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed)
      based on the probability of developing CDI (propensity score derived from patient
      characteristics). Exposed subjects were stratified by C. difficile test date,
      suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were
      analyzed for matched subjects. RESULTS: We identified 5107 exposed and 693 409
      unexposed subjects. Median age was 6 years (interquartile range [IQR], 2-13
      years) for exposed and 8 years (IQR, 3-14 years) for unexposed subjects. Of
      these, 4474 exposed were successfully matched to 8821 unexposed by propensity
      score. In-hospital mortality differed significantly (CDI, 1.43% vs matched
      unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and
      matched subjects. However, mortality rates were significantly greater among HO
      CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval
      {CI}, 3.77-12.02]). Mean differences in length of stay (LOS) and total cost were
      significant: 5.55 days (95% CI, 4.54-6.56 days) and $18 900 (95% CI, $15 100-$22
      700) for CO-CDI, and 21.60 days (95% CI, 19.29-23.90 days) and $93 600 (95% CI,
      $80 000-$107 200) for HO-CDI. CONCLUSIONS: Pediatric CDI is associated with
      increased mortality, longer LOS, and higher costs. These findings underscore the
      importance of antibiotic stewardship and infection control programs to prevent
      this disease in children.

PMID- 23532471
TI  - Editorial commentary: Clostridium difficile in children: colonization and
      consequences.

PMID- 23532472
TI  - An outbreak of acute Schistosoma mansoni Schistosomiasis in a nonendemic area of
      Brazil: a report on 50 cases, including 5 with severe clinical manifestations.
AB  - BACKGROUND: Acute schistosomiasis is a systemic hypersensitivity reaction against
      the migrating schistosomula and eggs. In this report, we describe an atypical
      outbreak of the disease with severe cases. Transmission occurred in a nonendemic
      area of Brazil, which became a new focus of transmission due to the in-migration
      of infected workers. METHODS: From December 2009 to March 2010, the 50 patients
      with acute schistosomiasis (group 1) bathed in a swimming pool supplied by a
      brook on a country estate in the outskirts of Sao Joao del Rei, Brazil. Thirty
      other subjects (group 2) living in the same area, who denied having contact with
      the swimming pool, volunteered to participate in the study. All participants were
      submitted to clinical, laboratory, and ultrasound examinations. RESULTS: Five of
      50 (10%) patients were admitted to the hospital: 1 with myeloradiculopathy, 1
      with diffuse pulmonary micronodules, and 3 with diarrhea and dehydration. All 5
      had hypereosinophilia and prolonged fever. Group 1 patients more frequently had
      cercarial dermatitis (P = .01), blood in the stool (P = .04), and intra-abdominal
      lymph nodes (P = .001). All group 1 patients were treated with praziquantel; 1
      patient with myeloradiculopathy also received oral prednisone (60 mg/day) for 6
      months with complete recovery. CONCLUSIONS: This report describes the first time
      that patients from an outbreak of acute schistosomiasis have been compared to
      controls. Five subjects (10%) had severe manifestations of schistosomiasis.
      Diagnosis of the disease and its severity was delayed because physicians did not
      consider that an epidemic of schistosomiasis might emerge in a nonendemic area.

PMID- 23532473
TI  - Immunotherapy for invasive mold disease in severely immunosuppressed patients.
AB  - Response to systemic antifungal therapy alone remains disproportionately less
      satisfactory in immunosuppressed transplant and oncology patients. As insight in
      fungal immunopathogenesis forges ahead, interventions for boosting immune
      functions along with antimicrobial drugs has shown promise in preclinical
      experiments. The clinical experience with immunotherapy for invasive mold disease
      is limited. Most studies have involved small numbers of patients at a single
      institution or data collected retrospectively. An overview of various facts of
      immune modulatory drug intervention is presented, including major considerations
      in antifungal immunotherapy in immunosuppressed patients. Patients in whom
      immunotherapy is being considered must be critically evaluated to identify the
      underlying immune defects, including treatment-induced immunosuppression.
      Antifungal immunotherapy is appealing; however, before routine clinical use is
      recommended, well-designed prospective comparative clinical trials are urgently
      needed.

PMID- 23532474
TI  - Immunoglobulin G anticardiolipin antibodies and progression to Q fever
      endocarditis.
AB  - BACKGROUND: Immunoglobulin G (IgG) anticardiolipin (aCL) antibodies are
      associated with valvulopathy and endocarditis in patients with lupus and other
      diseases. During acute Q fever, high IgG aCL prevalence has been reported, but
      the clinical significance remains unknown. METHODS: To test if increased IgG aCL
      at acute Q fever diagnosis is associated with an increased risk of progression to
      endocarditis, all patients diagnosed in the French National Referral Center for Q
      fever from January 2007 to December 2011 were included and followed regularly
      until January 2013 in a 5-year prospective cohort study. Q fever endocarditis was
      defined according to recently updated criteria. RESULTS: Seventy-two patients
      were followed for a median time of 31 months (interquartile range, 18-47 months).
      Of these, 13 patients with valvulopathy without antibiotic prophylaxis progressed
      to endocarditis. IgG aCL levels were highly prevalent (57%) and significantly
      higher in the presence of a valvulopathy (P = .005). Using Cox regression
      analysis, highly increased levels of IgG aCL (adjusted hazard ratio [AHR], 12.95;
      95% confidence interval, 2.85-58.95; P = .001) and high levels of phase II
      immunoglobulin M (IgM; AHR, 6.59; 95% CI, 1.37-31.62; P = .018) were the only
      independent predictors of progression to endocarditis. CONCLUSIONS: Rapid
      progression from acute Q fever to endocarditis is associated with high levels of
      IgG aCL and high levels of phase II IgM, findings that should be critical in the
      prevention of endocarditis.

PMID- 23532476
TI  - Automated surveillance for healthcare-associated infections: opportunities for
      improvement.
AB  - Surveillance of healthcare-associated infections is a cornerstone of infection
      prevention programs, and reporting of infection rates is increasingly required.
      Traditionally, surveillance is based on manual medical records review; however,
      this is very labor intensive and vulnerable to misclassification. Existing
      electronic surveillance systems based on classification algorithms using
      microbiology results, antibiotic use data, and/or discharge codes have increased
      the efficiency and completeness of surveillance by preselecting high-risk
      patients for manual review. However, shifting to electronic surveillance using
      multivariable prediction models based on available clinical patient data will
      allow for even more efficient detection of infection. With ongoing developments
      in healthcare information technology, implementation of the latter surveillance
      systems will become increasingly feasible. As with current predominantly manual
      methods, several challenges remain, such as completeness of postdischarge
      surveillance and adequate adjustment for underlying patient characteristics,
      especially for comparison of healthcare-associated infection rates across
      institutions.

PMID- 23532475
TI  - Influenza vaccine effectiveness in preventing outpatient, inpatient, and severe
      cases of laboratory-confirmed influenza.
AB  - BACKGROUND: In most seasons, the influenza vaccine is effective in preventing
      influenza, but it is not clear whether it is equally effective in preventing mild
      and severe cases. We designed a case-control study to compare the effectiveness
      of the influenza vaccine in preventing outpatient, inpatient, and severe or fatal
      cases of laboratory-confirmed influenza. METHODS: Hospitalized patients (n = 691)
      with laboratory-confirmed influenza in the 2010-2011 season recruited in 29
      Spanish hospitals were individually matched by age, admission/visit date, and
      province with an outpatient with laboratory-confirmed influenza and an outpatient
      control. Severe cases were considered those patients admitted to intensive care
      units or who died in the hospital (n = 177). We compared the influenza vaccine
      status of controls and outpatient cases, inpatient cases, and severe cases using
      conditional logistic regression adjusted for potential confounding factors.
      Severe and nonsevere inpatient influenza cases were compared using unconditional
      logistic regression. Vaccine effectiveness was (1 - odds ratio) * 100. RESULTS:
      Vaccine effectiveness was 75% (adjusted odds ratio [AOR], 0.25; 95% confidence
      interval [CI], .16-.39) in preventing influenza outpatient cases, 60% (AOR, 0.40;
      95% CI, .25-.63) in preventing influenza-associated hospitalizations, and 89%
      (AOR, 0.11; 95% CI, .04-.37) in preventing severe cases. In inpatients, influenza
      vaccination was associated with a lower risk of severe influenza (AOR, 0.42; 95%
      CI, .22-.80). CONCLUSIONS: Influenza vaccination prevented influenza cases and
      hospitalizations and was associated with a better prognosis in inpatients with
      influenza. The combined effect of these 2 mechanisms would explain the high
      effectiveness of the vaccine in preventing severe cases due to influenza.

PMID- 23532478
TI  - Improvement and advancement of early diagnosis of human brucellosis in window
      period.

PMID- 23532477
TI  - Changes in HIV-1 subtypes B and C genital tract RNA in women and men after
      initiation of antiretroviral therapy.
AB  - BACKGROUND: Combination antiretroviral therapy (cART) reduces genital tract human
      immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual
      transmission, but little is known about the efficacy of cART for decreasing
      genital tract viral load (GTVL) and differences in sex or HIV-1 subtype. METHODS:
      HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at
      baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3
      cART regimens. RESULTS: One hundred fifty-eight men and 170 women from 7
      countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype
      B and 76% subtype C). Despite similar baseline CD4(+) cell counts and blood
      plasma viral loads, women with subtype C had the highest GTVL (median, 5.1 log10
      copies/mL) compared to women with subtype B and men with subtype C or B (4.0,
      4.0, and 3.8 log10 copies/mL, respectively; P < .001). The proportion of
      participants with a GTVL below the lower limit of quantification (LLQ) at week 48
      (90%) and week 96 (90%) was increased compared to baseline (16%; P < .001 at both
      times). Women were significantly less likely to have GTVL below the LLQ compared
      to men (84% vs 94% at week 48, P = .006; 84% vs 97% at week 96, P = .002),
      despite a more sensitive assay for seminal plasma than for cervical wicks. No
      difference in GTVL response across the 3 cART regimens was detected. CONCLUSIONS:
      The female genital tract may serve as a reservoir of persistent HIV-1 replication
      during cART and affect the use of cART to prevent sexual and perinatal
      transmission of HIV-1.

PMID- 23532480
TI  - Incident hepatitis C virus infection in men who have sex with men: a prospective
      cohort analysis, 1984-2011.
AB  - BACKGROUND: Prospective characterization of hepatitis C virus (HCV) transmission
      in both human immunodeficiency virus (HIV)-infected and -uninfected men who have
      sex with men (MSM) over the entire HIV epidemic has not been comprehensively
      conducted. METHODS: To determine the trends in and risk factors associated with
      incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)-negative MSM in the
      Multicenter AIDS Cohort Study were prospectively followed during 1984-2011 for
      anti-HCV seroconversion. RESULTS: During 55 343 person-years (PYs) of follow-up,
      there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered
      throughout the study period. In a multivariable analysis with time-varying
      covariates, older age (incidence rate ratio [IRR], 1.40/10 years, P < .001),
      enrollment in the later (2001-2003) recruitment period (IRR, 3.80, P = .001), HIV
      infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR,
      1.68, P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001),
      syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with
      >1 male partner (IRR, 3.37, P < .001) were independently associated with incident
      HCV. Among HIV-infected subjects, every 100 cell/mm(3) increase in CD4 count was
      associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4
      count of 500 cells/mm(3), whereas there was no association with highly active
      antiretroviral therapy. CONCLUSIONS: The spread of HCV among both HIV-infected
      and -uninfected MSM in the United States has been ongoing since the beginning of
      the HIV epidemic. In HIV-infected men with <500 CD4(+) T cells, the HCV incidence
      rate was inversely proportional to CD4 T-cell count.

PMID- 23532481
TI  - Infectious complications following transrectal ultrasound-guided prostate biopsy:
      new challenges in the era of multidrug-resistant Escherichia coli.
AB  - Transrectal ultrasound (TRUS)-guided prostate biopsy is currently considered the
      standard technique for obtaining tissue to make a histological diagnosis of
      prostatic carcinoma. Infectious complications following TRUS-guided prostate
      biopsy are well described, and are reportedly increasing in incidence. The role
      of antibiotic prophylaxis in reducing post-TRUS biopsy infections is now
      established, and many guidelines suggest that fluoroquinolone antimicrobials are
      the prophylactic agents of choice. Of note, however, recent reports suggest an
      emerging association between TRUS biopsy and subsequent infection with
      fluoroquinolone-resistant Escherichia coli. Against this background, we provide
      an overview of the epidemiology, prevention, and treatment of infectious
      complications following TRUS biopsy, in the wider context of increasing global
      antimicrobial resistance. 

PMID- 23532482
TI  - Climate change impacts on potential recruitment in an ecosystem engineer.
AB  - Climate variability and the rapid warming of seas undoubtedly have huge
      ramifications for biological processes such as reproduction. As such,
      gametogenesis and spawning were investigated at two sites over 200 km apart on
      the south coast of Ireland in an ecosystem engineer, the common cockle,
      Cerastoderma edule. Both sites are classed as Special Areas of Conservation
      (SACs), but are of different water quality. Cerastoderma edule plays a
      significant biological role by recycling nutrients and affecting sediment
      structure, with impacts upon assemblage biomass and functional diversity. It
      plays a key role in food webs, being a common foodstuff for a number of marine
      birds including the oystercatcher. Both before and during the study (early 2010
      mid 2011), Ireland experienced its two coldest winters for 50 years. As the
      research demonstrated only slight variation in the spawning period between sites,
      despite site differences in water and environmental quality, temperature and
      variable climatic conditions were the dominant factor controlling gametogenesis.
      The most significant finding was that the spawning period in the cockle extended
      over a greater number of months compared with previous studies and that
      gametogenesis commenced over winter rather than in spring. Extremely cold winters
      may impact on the cockle by accelerating and extending the onset and development
      of gametogenesis. Whether this impact is positive or negative would depend on the
      associated events occurring on which the cockle depends, that is, presence of
      primary producers and spring blooms, which would facilitate conversion of this
      extended gametogenesis into successful recruitment.

PMID- 23532483
TI  - [Surgery with passion and a sense of proportion].

PMID- 23532484
TI  - [Abdominal organ retrieval: strategies to improve quality].
AB  - The blatant problem of organ shortage leads to an increasing acceptance of organs
      from extended criteria donors. This increases the importance of the process of
      organ donation and retrieval. A working group of representatives of Bavarian
      retrieval surgeons and the procurement organization German Foundation of Organ
      Transplantation (DSO) was initiated to develop consensus-based recommendations
      for quality improvements in the field of organ retrieval on the basis of regional
      data. The main aim was to professionalize retrieval teams by specified training
      standards and to define objective qualifications for retrieval surgeons. Initial
      measures of the working group included agreement on standardized retrieval
      techniques and improvement of documentation in terms of quality forms and the
      return rate of the forms. Quality data are being analyzed prospectively with a
      new categorization of complications. Communication among centers and teams and
      complication reporting has already been improved and initial structural changes
      have been set up.

PMID- 23532485
TI  - [Patient rights act: effect on medical practice].

PMID- 23532486
TI  - [Recruiting multicenter surgical studies in Germany].

PMID- 23532488
TI  - Factors affecting range of motion in total knee arthroplasty using high flexion
      prosthesis: A prospective study.
AB  - BACKGROUND: High flexion implants have been reported to provide better range of
      motion (ROM). The few studies analyzing the factors affecting the ROM are scarce.
      This study aims to find the factors that affect ROM when using a high flex knee
      design (INDUS knee). MATERIALS AND METHODS: Two hundred and fifty three
      consecutive patients of total knee arthroplasty (TKA) done by using INDUS knee
      prosthesis between Sept 2008 and Sept 2009 were included in the study. The cases
      with osteoarthritis (OA) and Rheumatoid arthritis (RA) were included in study. 5
      patients were lost to followup and 248 patients (267 knees, 19 bilateral, 221 OA,
      and 46 RA) were analyzed for the following factors - sex, age, body mass index
      (BMI), preoperative ROM, flexion deformity, preoperative total knee score and
      functional score, time of tourniquet release and patella resurfacing. Subgroup
      classification using above factors was performed and statistical analysis of
      effect of all the above factors on final knee ROM was done. Assessment was done
      preoperatively and at 3 months, 6 months and 1 year postoperatively. The final
      outcome evaluation was done at one year followup. RESULTS: The mean age was 68.2
      years (range 40-89 years) with 79 males and 189 females. The mean knee range
      improved from 97.62 +/- 11 degrees  to 132 +/- 8 degrees . Factors that
      positively affect ROM of INDUS knee prosthesis at the end of 1 year were
      preoperative ROM, total knee score and functional score, and diagnosis of
      osteoarthritis, whereas BMI, preoperative flexion deformity has a negative
      influence on final flexion at the end of 1 year. Age and gender of the patients,
      patella resurfacing, and use of two different tourniquet protocols did not affect
      the final outcome. CONCLUSION: Preoperative ROM and preoperative functional
      status are the most important factors affecting final range. Patients should be
      counseled accordingly and made to understand these factors.

PMID- 23532489
TI  - Inpatient weight loss as a precursor to bariatric surgery for adolescents with
      extreme obesity: optimizing bariatric surgery.
AB  - BACKGROUND: As the obesity epidemic takes its toll on patients stricken with the
      disease and our health care system, debate continues regarding the use of weight
      loss surgery and its long-term consequences, especially for adolescents. One
      subset of patients regarding whom there is increased controversy is adolescents
      with extreme obesity (BMI > 60 kg/m(2)) because the risk of complications in this
      weight category is higher than for others undergoing bariatric surgery. Several
      strategies have been suggested for this patient group, including staged
      operations, combined operations, intragastric balloon use, and endoluminal sleeve
      placement. However, the device options are often not available to adolescents,
      and there are no data regarding staged or combined procedures in this age group.
      METHODS: All adolescents with BMI >60 kg/m(2) referred to our program were
      evaluated for inpatient medical weight loss prior to laparoscopic sleeve
      gastrectomy. The program utilizes a multidisciplinary approach with a protein
      sparing modified fast diet, exercise, and behavioral modification. RESULTS: Three
      patients completed the program, and each achieved significant preoperative weight
      loss through the inpatient program and successfully underwent bariatric surgery.
      CONCLUSIONS: Presurgical weight loss via an inpatient program for adolescents
      with a BMI >60 kg/m(2) results in total weight loss comparable to a primary
      surgical procedure alone, with the benefit of decreasing the perioperative risk.

PMID- 23532490
TI  - Perceptions about eating healthy in WIC participants.

PMID- 23532487
TI  - [Antireflux operations: indications and techniques].
AB  - In severe gastroesophageal reflux disease fundoplication is a sound therapeutic
      alternative if long-term treatment with proton pump inhibitors is not a viable
      option. However, careful patient selection is mandatory and reflux disease has to
      be proven objectively. Patients who are particularly prone to develop
      postoperative functional side effects should be excluded.For surgical treatment
      either a 360 degrees  wrap (Nissen) or a 270 degrees  wrap (Toupet) can be
      performed with more or less equivalent results. The common technical denominators
      are to achieve a loose, short wrap. In both instances the cuff has to be fixed
      securely with non-absorbable sutures and any damage to the vagal innervation has
      to be avoided.Long-term reflux prevention is excellent and superior to medical
      treatment; nonetheless, functional side effects still occur and to keep the
      incidence as low as possible preoperative selection of patients is essential.

PMID- 23532491
TI  - A case of glioblastoma invasion clearly demonstrated on 11C-methionine positron
      emission tomography.

PMID- 23532492
TI  - Burden of cancer incidence below the age of 40 in Asia 2002 extrapolated from the
      Cancer Incidence in Five Continents Vol. IX.

PMID- 23532479
TI  - Contribution of genetic background, traditional risk factors, and HIV-related
      factors to coronary artery disease events in HIV-positive persons.
AB  - BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have
      increased rates of coronary artery disease (CAD). The relative contribution of
      genetic background, HIV-related factors, antiretroviral medications, and
      traditional risk factors to CAD has not been fully evaluated in the setting of
      HIV infection. METHODS: In the general population, 23 common single-nucleotide
      polymorphisms (SNPs) were shown to be associated with CAD through genome-wide
      association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white
      individuals enrolled in 24 HIV observational studies, including 571 participants
      with a first CAD event during the 9-year study period and 1304 controls matched
      on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated
      SNPs contributed significantly to CAD (P = 2.9 * 10(-4)). In the final
      multivariable model, participants with an unfavorable genetic background (top
      genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence
      interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36;
      95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes
      (OR = 1.66; 95% CI, 1.10-2.49), >= 1 year lopinavir exposure (OR = 1.36; 95% CI,
      1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The
      effect of the genetic risk score was additive to the effect of nongenetic CAD
      risk factors, and did not change after adjustment for family history of CAD.
      CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable
      genetic background was similar to traditional CAD risk factors and certain
      adverse antiretroviral exposures. Genetic testing may provide prognostic
      information complementary to family history of CAD.

PMID- 23532494
TI  - Mislabelled cow's milk allergy in infants: a prospective cohort study.
AB  - BACKGROUND: Although cow's milk allergy (CMA) is one of the most common food
      allergies, mislabelling non-allergic infants as being allergic to cow's milk is
      more common. Despite this, characteristics of families and infants with
      mislabelled CMA are lacking. METHODS: Using a prospective population-based study,
      we identified infants with any possible adverse reaction to cow's milk (n=381)
      from a cohort of 13 019 infants followed from birth. They had a detailed history
      taken, skin prick tests and an oral food challenge when indicated. Infants with
      symptoms for which the causative relationship to cow's milk protein was excluded
      were compared with infants with IgE-mediated CMA and with a control group, and
      followed for 2-5 years. RESULTS: Overall, 243 infants (1.87%) with mislabelled
      CMA were identified. Compared with 66 infants with IgE-mediated CMA, those with
      mislabelled CMA presented earlier and with symptoms usually involving a single
      organ system. Doctor-diagnosed atopic dermatitis (AD) was associated with
      mislabelled CMA (p<0.001), manifested primarily as skin rashes, compared with
      control infants. Higher maternal and paternal education were also associated with
      mislabelled CMA (p=0.007 and p=0.035, respectively) and manifested primarily as
      non-specific symptoms. CONCLUSIONS: Mislabelled CMA typically presents within the
      first 3 months of life involving a single organ. Infant AD and higher parental
      academic education are associated with mislabelled reactions. Better parental and
      physician awareness of the importance of objectively diagnosing milk allergy is
      required to avoid mislabelling of infants as being allergic to cow's milk and to
      prevent potential nutritional deficiencies.

PMID- 23532493
TI  - Drug treatment of inborn errors of metabolism: a systematic review.
AB  - BACKGROUND: The treatment of inborn errors of metabolism (IEM) has seen
      significant advances over the last decade. Many medicines have been developed and
      the survival rates of some patients with IEM have improved. Dosages of drugs used
      for the treatment of various IEM can be obtained from a range of sources but tend
      to vary among these sources. Moreover, the published dosages are not usually
      supported by the level of existing evidence, and they are commonly based on
      personal experience. METHODS: A literature search was conducted to identify key
      material published in English in relation to the dosages of medicines used for
      specific IEM. Textbooks, peer reviewed articles, papers and other journal items
      were identified. The PubMed and Embase databases were searched for material
      published since 1947 and 1974, respectively. The medications found and their
      respective dosages were graded according to their level of evidence, using the
      grading system of the Oxford Centre for Evidence-Based Medicine. RESULTS: 83
      medicines used in various IEM were identified. The dosages of 17 medications
      (21%) had grade 1 level of evidence, 61 (74%) had grade 4, two medications were
      in level 2 and 3 respectively, and three had grade 5. CONCLUSIONS: To the best of
      our knowledge, this is the first review to address this matter and the authors
      hope that it will serve as a quickly accessible reference for medications used in
      this important clinical field.

PMID- 23532495
TI  - Chemosensory TRP channels in the respiratory tract: role in toxic lung injury and
      potential as "sweet spots" for targeted therapies.
AB  - Acute toxic lung injury by reactive inhalational compounds is an important and
      still unresolved medical problem. Hazardous gases or vapors, e. g. chlorine,
      phosgene, sulfur mustard or methyl isocyanate, are released during occupational
      accidents or combustion processes and also represent a potential threat in
      terroristic scenarios. According to their broad-range chemical reactivity, the
      mechanism of lung injury evoked by these agents has long been described as rather
      unspecific. Consequently, therapeutic options are still restricted to symptomatic
      treatment. However, in recent years, ion channels of the transient receptor
      potential (TRP) family have been identified to act as specific sensor molecules
      expressed in the respiratory tract and to engage defined signaling pathways upon
      inhalational exposure to toxic challenges. These pulmonary receptor molecules
      have been primarily characterized in sensory neurons of the lung. However,
      chemosensory molecules are also expressed in non-neuronal cells, e.g. in the lung
      epithelium as well as in the pulmonary vasculature. Thus, activation of
      respiratory chemosensors by toxic inhalants promotes a complex signaling network
      directly or indirectly regulating pulmonary blood flow, the integrity of the
      epithelial lining, and the mucociliary clearance of the bronchial system. This
      review gives a synopsis on reactive lung-toxic agents and their specific target
      molecules in the lung and summarizes the current knowledge about the
      pathophysiological role of chemosensory signaling in neuronal and non-neuronal
      cells in toxic lung injury. Finally, we describe possible future strategies for a
      causal, specifically tailored treatment option based on the mechanistic
      understanding of molecular events ensuing inhalation of lung-toxic agents. 

PMID- 23532496
TI  - LiCu2[BP2O8(OH)2]: a chiral open-framework copper borophosphate via spontaneous
      asymmetrical crystallization.
AB  - A new chiral copper borophosphate, LiCu2[BP2O8(OH)2] (1), was crystallized from
      achiral inorganic raw materials in boric acid flux reaction. The structure
      features a 9-ring channel enclosed by triple right-handed helices. The bulk
      sample exhibits optical activity confirmed by circular dichroism (CD) spectra,
      indicating an interesting spontaneous resolution phenomenon.

PMID- 23532497
TI  - Serum levels of calreticulin in correlation with disease activity in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: The aim of our study was to investigate the contribution of serum
      calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis
      (RA). METHODS: Serum CRT levels were measured by ELISA in 70 patients with
      established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune
      diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations
      of CRT serum levels with disease activity [Disease Activity Score for 28 joints
      (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were
      assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP
      and anti- MCV antibodies were positive and negative. RESULTS: Serum CRT levels in
      RA patients (4.817 +/- 2.425 ng/ml) was significantly higher (P <0.05) compared
      with those in the serum of OA (3.574 +/- 0.942 ng/ml), SLE (4.013 +/- 1.536
      ng/ml), other autoimmune diseases (3.882 +/- 0.837 ng/ml) and HC (3.726 +/- 0.627
      ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found
      in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies
      were positive had higher levels of CRT (P < 0.01). CONCLUSION: Serum CRT levels
      were increased in patients with RA compared with those controls. Moreover, a
      significant correlation was observed between serum CRT levels and disease
      activity in RA. It might be used as a potential biomarker for clinical diagnosis
      and provide additional information regarding disease activity along with the
      traditional indices such as ESR and CRP.

PMID- 23532498
TI  - Letter to the editor re: positron emission tomography with [(18)F]-3'-deoxy
      3'fluorothymidine (FLT) as a predictor of outcome in patients with locally
      advanced resectable rectal cancer: a pilot study.

PMID- 23532500
TI  - The sEDA(=) and pEDA(=) descriptors of the double bonded substituent effect.
AB  - New descriptors of the double bonded substituent effect, sEDA(=) and pEDA(=),
      were constructed based on quantum chemical calculations and NBO methodology. They
      show to what extent the sigma and pi electrons are donated to or withdrawn from
      the substituted system by a double bonded substituent. The new descriptors differ
      from descriptors of the classical substituent effect for which the pz orbital of
      the ipso carbon atom is engaged in the pi-electron system of the two neighboring
      atoms in the ring. For double bonded substituents, the pz orbital participates in
      double bond formation with only one external atom. Moreover, the external double
      bond forces localization of the double bond system of the ring, significantly
      changing the core molecule. We demonstrated good agreement between our
      descriptors and the Weinhold and Landis' "natural sigma and pi
      electronegativities": so far only descriptors allowing for evaluation of the
      substitution effect by a double bonded atom. The equivalency between descriptors
      constructed for 5- and 6-membered model structures as well as linear
      dependence/independence of the constructed parameters was discussed. Some
      interrelations between sEDA(=) and pEDA(=) and the other descriptors of
      (hetero)cyclic systems such as aromaticity and electron density in the ring and
      bond critical points were also examined.

PMID- 23532499
TI  - Risk-based prostate cancer screening: who and how?
AB  - The purpose of this review is to identify clinical risk factors for prostate
      cancer and to assess the utility and limitations of our current tools for
      prostate cancer screening. Prostate-specific antigen is the single most important
      factor for identifying men at increased risk of prostate cancer but is best
      assessed in the context of other clinical factors; increasing age, race, and
      family history are well-established risk factors for the diagnosis of prostate
      cancer. In addition to clinical risk calculators, novel tools such as
      multiparametric imaging, serum or urinary biomarkers, and genetic profiling show
      promise in improving prostate cancer diagnosis and characterization. Optimal use
      of existing and future tools will help alleviate the problems of overdiagnosis
      and overtreatment of low-risk prostate cancer without reversing the substantial
      mortality declines that have been achieved in the screening era.

PMID- 23532501
TI  - Brain metastases from papillary thyroid carcinomas.
AB  - Brain metastasis from papillary thyroid carcinoma (PTC) is extremely rare and
      carries a poor prognosis. We report nine cases (five females and four males) of
      brain metastasis of PTC. The age of patients ranged from 46 to 87 years old. The
      patients presented with nonspecific symptoms such as headaches. Brain metastasis
      was the first clinical presentation in three of nine patients; two of which had
      the aggressive tall cell variant of PTC. Six patients had prior history of PTC
      (four classic, one oncocytic variant, and one columnar cell variant) for 2 to 17
      years with a median of 12 years. Gross total resection of brain metastasis was
      achieved for eight of our patients. Eight patients were treated with radioactive
      iodine. The median follow-up time was 12 months, ranging from 1 month to 4 years.
      Three patients died of their disease in 6 months, 21 months and 4 years,
      respectively after their first presentation of brain metastasis. It seems that
      these rare aggressive variants of PTC, such as tall cell variant, not only have
      higher propensity to develop brain metastasis, but also more frequently present
      with brain metastasis as their first clinical presentation than classic PTC.
      Furthermore, patients with PTC can develop brain metastasis even after many
      years.

PMID- 23532502
TI  - Follicular epithelial dysplasia of the thyroid: morphological and
      immunohistochemical characterization of a putative preneoplastic lesion to
      papillary thyroid carcinoma in chronic lymphocytic thyroiditis.
AB  - In chronic lymphocytic thyroiditis (CLT), the follicular epithelial cells display
      cytological atypia resembling papillary thyroid carcinoma (PTC), and
      epidemiological studies have suggested an increased risk of PTC in patients with
      this condition. While reactive atypia is observed diffusely in CLT-affected
      thyroid parenchyma, it is not unusual to find microscopic foci morphologically
      distinct from the surrounding parenchyma, exhibiting more pronounced cytological
      and architectural atypia. These small atypical lesions, which we term "follicular
      epithelial dysplasia" (FED), are particularly prominent in cases of severe CLT,
      yet lack invasive growth, papillary architecture, or intranuclear
      pseudoinclusions. To gain further insight into their biological significance, we
      constructed a tissue microarray of 70 cases of CLT, comprised of morphologically
      normal thyroid, thyroid with reactive atypia, FED, follicular nodular disease
      (nodular hyperplasia or follicular adenoma), and PTC. Immunohistochemical
      staining was performed for a marker panel including PTC (HBME-1, cytokeratin 19,
      galectin-3, and cyclin-D1) as well as TTF-1, thyroglobulin, and p63. Slides were
      digitally scanned and immunohistochemical staining evaluated using automated
      image analysis software. FED lesions were positive for TTF-1 and thyroglobulin
      (50/50, 100 %), though some (13/50, 26 %) also expressed p63. Similar to PTC,
      strong diffuse staining was observed for HBME-1 (43/50, 86 %), cytokeratin 19
      (48/50, 96 %), galectin-3 (20/50, 40 %) and cyclin-D1 (38/50, 76 %). In contrast,
      normal thyroid, reactive atypia, and follicular nodular disease were negative, or
      at most, exhibited focal weak staining for HBME-1, cytokeratin 19, and galectin
      3. The results of this study demonstrate the presence of atypical microscopic
      lesions in CLT with an immunohistochemical profile similar to PTC, supporting the
      concept of a premalignant lesion preceding PTC, arising in the context of severe
      chronic inflammation.

PMID- 23532503
TI  - Fidelity among Sirex woodwasps and their fungal symbionts.
AB  - We report that associations between mutualistic fungi and their economically and
      ecologically important woodwasp hosts are not always specific as was previously
      assumed. Woodwasps in the genus Sirex engage in obligate nutritional
      ectosymbioses with two species of Amylostereum, a homobasid?iomycete genus of
      white rot fungi. In the present study, the Amylostereum species and genotypes
      associated with three species of Sirex native to eastern North America and one
      relatively recent invasive Sirex from Europe were investigated by comparing
      intergenic spacer regions (IGS). Sirex spp. were sampled over 6 years from 23
      sites in six US states, ranging from Maine in the northeast to Louisiana in the
      southeast, to obtain samples of Amylostereum from mycangia of adult females. Two
      of the native Sirex species (Sirex nigricornis and Sirex nitidus) were associated
      with either Amylostereum chailletii or Amylostereum areolatum, refuting the
      hypothesis of strict species-specific relationships. However, the invasive Sirex
      noctilio and the native Sirex cyaneus were each collected with only A. areolatum
      or A. chailletii, respectively, although S. noctilio was associated with two
      different IGS genotypes of A. areolatum and S. cyaneus occurs sympatrically with
      the other native Sirex. In Pinus, the preferred host tree of S. nigricornis and
      S. noctilio, these species co-occurred in 25.9 % of trees sampled, and horizontal
      transmission of fungal strains from S. noctilio to S. nigricornis was documented,
      although only in one tree. The extent that further spread and establishment of S.
      noctilio will alter the composition of symbionts carried by native Sirex is
      unknown but will depend in part on the degree of flexibility in these host
      symbiont associations.

PMID- 23532504
TI  - [Pathophysiology of acne. What is confirmed?].
AB  - Acne is the most common skin disease worldwide. Choosing the appropriate
      therapeutic regimens for the clinically diversified disease phenotypes require
      good knowledge of its pathophysiology. New concepts in this field have been
      developed in the last 15 years. Acne vulgaris is an inflammatory disorder in
      which androgens, PPAR ligands, regulating neuropeptides and environmental factors
      are probably involved as triggers. These factors interrupt the natural cycling
      process in the sebaceous gland follicle and support the transition of
      microcomedones to comedones and clinically inflammatory lesions. Proinflammatory
      lipids, chemokines and cytokines overtake the role of mediators for the further
      development of acne lesions. Bacterial antigens can potentate the inflammatory
      phenomena.

PMID- 23532505
TI  - [Molecular biological detection of dermatophytes in clinical samples when
      onychomycosis or tinea pedis is suspected. A prospective study comparing
      conventional dermatomycological diagnostics and polymerase chain reaction].
AB  - BACKGROUND: The prevalence of onychomycosis is rising worldwide. Before starting
      antifungal treatment, an exact mycological diagnosis should be obtained. The
      current laboratory diagnosis of dermatomycoses is based on the detection of the
      causative agent by microscopy and culture. These conventional diagnostic methods
      for fungal infections often are not the best solution because they are time
      consuming, cultures are false-negative and direct examination identifies non
      vital structures which cannot be used for speciation. PATIENTS AND METHODS: A
      total of 218 patients presenting in a surgical practice over 3 months with
      clinical signs of tinea pedis and/or onychomycosis were involved in the
      prospective study. All patients had predisposing factors for tinea pedis and
      tinea unguium, such as vascular insufficiency, diabetes mellitus, and leg ulcers.
      Nail specimens and skin scrapings were investigated for fungi using Blancophor(r)
      preparation, and cultured. In addition to conventional diagnostics, PCR
      (polymerase chain reaction) for detection of dermatophyte DNA was employed. This
      PCR-Elisa assay is based on the use of specific primers which target the
      topoisomerase II gene. This allows the highly specific molecular identification
      of Trichophyton (T.) rubrum, T. interdigitale, and Epidermophyton floccosum
      directly in clinical samples. RESULTS: 23.9 % of patients were culture-positive
      for dermatophytes (either T. rubrum, or T. interdigitale). With PCR, dermatophyte
      DNA either of T. rubrum or T. interdigitale could be detected in nail samples and
      skin scrapings from at least 29.9 % of all patients. Epidermophyton floccosum was
      not found in this study, neither by cultivation nor by PCR. The diagnostic
      sensitivity of the PCR-Elisa assay was calculated as 79.0% ; the diagnostic
      specificity as 85.5 %. CONCLUSION: PCR-Elisa evaluation makes possible a rapid,
      specific and sensitive diagnosis of dermatophytosis of the nails and skin within
      24 (maximal 48) hours with identification of the involved species.

PMID- 23532506
TI  - Does melatonin affect epileptic seizures?
AB  - Melatonin is widely used for sleep disorders in patients with a range of
      developmental disorders and neurodisabilities, who also frequently have epilepsy.
      The aim of our review was to examine published data to assess the evidence for
      melatonin affecting seizure control. The literature search revealed 26 papers
      apparently reporting an association between melatonin and epilepsy or seizures
      but seven of these did not provide relevant information. Of the three double
      blind, randomised, controlled trials, two showed no overall worsening or
      improvement in seizures, and one recent trial reported a statistically
      significant reduction in seizures. The open studies reported conflicting results.
      The few studies on the effect of seizures on melatonin levels have reported that
      baseline melatonin levels may be low in patients with uncontrolled epilepsy and
      that levels increase markedly following seizures. The striking finding of this
      review is the paucity of relevant data from the remarkably small number of
      studies. These results allow no firm conclusions to be drawn, although it would
      seem reasonable to observe that there was no marked overall effect on seizures,
      neither improvement nor worsening. There is a need for large, well designed,
      randomised, double-blind, placebo-controlled trials to establish the role of
      melatonin in either predisposing to or decreasing the likelihood of seizures.

PMID- 23532508
TI  - Biventricular mechanics in constrictive pericarditis comparison with restrictive
      cardiomyopathy and impact of pericardiectomy.
AB  - BACKGROUND: The aim of our study was to compare myocardial mechanics of
      constrictive pericarditis (CP) with restrictive cardiomyopathy (RCM), or healthy
      controls; to assess the impact of pericardial thickening detected by cardiac
      magnetic resonance on regional myocardial mechanics in CP; and to quantitate the
      effect of pericardiectomy on myocardial mechanics in CP. METHODS AND RESULTS:
      Myocardial mechanics were evaluated by 2-dimensional speckle tracking in 52
      consecutive patients with CP who underwent cardiac magnetic resonance examination
      before pericardiectomy, 35 patients with RCM, and 26 control subjects. CP
      patients had selectively depressed left ventricular (LV) anterolateral wall
      strain (LWS) and right ventricular (RV) free wall longitudinal systolic strain
      (FWS) but preserved LV septal wall systolic strain (SWS). In a comparison of RCM
      and normals, CP patients had significantly lower regional longitudinal systolic
      strain ratios (CP versus RCM and normal; LVLWS/LVSWS: 0.8+/-0.2 versus 1.1+/-0.2
      and 1.0+/-0.2; P<0.001, RVFWS/LVSWS: 0.8+/-0.4 vs. 1.4+/-0.5 and 1.2+/-0.2;
      P<0.001). LVLWS/LVSWS was more robust than the LV lateral wall to LV septal wall
      ratio of early diastolic velocities at the LV base (LE'/SE') in differentiating
      CP from RCM (area under the curve=0.91 versus 0.76; P=0.011). There was a
      significant inverse correlation between pericardial thickness and respective
      ventricular strains (P=0.001). Pericardiectomy resulted in the improvement of the
      depressed LVLWS/LVSWS (0.83+/-0.18-0.95+/-0.12; P<0.001). CONCLUSIONS: Regional
      longitudinal systolic strain ratios are robust novel diagnostic tools for CP.
      Regional myocardial mechanics inversely correlates with adjacent pericardial
      segment thickness detected by cardiac magnetic resonance, and pericardiectomy
      leads to systolic strain improvement, which is more pronounced in right
      ventricular and LV free walls.

PMID- 23532507
TI  - Adhesive properties of predominant bacteria in raw cow's milk to bovine mammary
      gland epithelial cells.
AB  - Various bacteria have been found in raw cow's milk, and identifying milk
      microflora and its functions is critical for maintaining cow health and farm
      hygiene. Although studies on pathogens and spoilage bacteria in milk have been
      widely reported, the relationship between milk bacteria, including nonpathogenic
      bacteria, and the bovine udder is poorly understood. We investigated milk
      microflora over 1 year using a culture-dependent method and culture-independent
      analysis by denaturing gradient gel electrophoresis. Among 240 isolates,
      Lactococcus lactis (81/240) was predominant. The predominant genera were
      Lactococcus, Stenotrophomonas, Microbacterium, Chryseobacterium, Serratia and
      Pseudomonas. Among seven strains belonging to these predominant genera, two
      strains of L. lactis (ssp. lactis and ssp. cremoris) exhibited the highest
      adherence to bovine mammary gland epithelial cells (BMECs) derived from the
      bovine udder; 3.4 % of the inoculated bacteria adhered to BMECs. This was
      followed by Serratia sp. (1.6 %), Microbacterium sp. (0.8 %), Stenotrophomonas
      maltophilia (0.5 %), Pseudomonas sp. (0.3 %) and Chryseobacterium sp. (0.1 %).
      The two L. lactis isolates exhibited higher adherence to BMECs than type strains
      and isolates of various origins. 

PMID- 23532509
TI  - Neuromodulatory systems.
AB  - We examine the interactions and interdependencies between Neuroglia, the Brain
      Cell Microenvironment, and the processes commonly subsumed under Neuromodulation.
      The interactions of the component processes covering a wide spectrum of
      frequencies are designated as Neuromodulatory Systems (NMS). This implies NMS's
      scale-invariance as the capacity of linking actions across many time scales, and
      self-similarity at any scale. These features endow NMS with the ability to
      respond adaptively to neural impulse traffic of an unpredictably wide frequency
      spectrum. In this preliminary perspective, the components of NMS are only
      outlined based on concepts of Complex Systems Dynamics. However, their
      interactions must be formally elaborated in further investigations.

PMID- 23532510
TI  - Integrated methodology for assessing the HCH groundwater pollution at the multi
      source contaminated mega-site Bitterfeld/Wolfen.
AB  - A large-scale groundwater contamination characterises the Pleistocene groundwater
      system of the former industrial and abandoned mining region Bitterfeld/Wolfen,
      Eastern Germany. For more than a century, local chemical production and extensive
      lignite mining caused a complex contaminant release from local production areas
      and related dump sites. Today, organic pollutants (mainly organochlorines) are
      present in all compartments of the environment at high concentration levels. An
      integrated methodology for characterising the current situation of pollution as
      well as the future fate development of hazardous substances is highly required to
      decide on further management and remediation strategies. Data analyses have been
      performed on regional groundwater monitoring data from about 10 years, containing
      approximately 3,500 samples, and up to 180 individual organic parameters from
      almost 250 observation wells. Run-off measurements as well as water samples were
      taken biweekly from local creeks during a period of 18 months. A kriging
      interpolation procedure was applied on groundwater analytics to generate
      continuous distribution patterns of the nodal contaminant samples. High
      resolution geological 3-D modelling serves as a database for a regional 3-D
      groundwater flow model. Simulation results support the future fate assessment of
      contaminants. A first conceptual model of the contamination has been developed to
      characterise the contamination in regional surface waters and groundwater. A
      reliable explanation of the variant hexachlorocyclohexane (HCH) occurrence within
      the two local aquifer systems has been derived from the regionalised distribution
      patterns. Simulation results from groundwater flow modelling provide a better
      understanding of the future pollutant migration paths and support the overall
      site characterisation. The presented case study indicates that an integrated
      assessment of large-scale groundwater contaminations often needs more data than
      only from local groundwater monitoring. The developed methodology is appropriate
      to assess POP-contaminated mega-sites including, e.g. HCH deposits. Although HCH
      isomers are relevant groundwater pollutants at this site, further organochlorine
      pollutants are present at considerably higher levels. The study demonstrates that
      an effective evaluation of the current situation of contamination as well as of
      the related future fate development requires detailed information of the entire
      observed system.

PMID- 23532511
TI  - Cross-validation for nonlinear mixed effects models.
AB  - Cross-validation is frequently used for model selection in a variety of
      applications. However, it is difficult to apply cross-validation to mixed effects
      models (including nonlinear mixed effects models or NLME models) due to the fact
      that cross-validation requires "out-of-sample" predictions of the outcome
      variable, which cannot be easily calculated when random effects are present. We
      describe two novel variants of cross-validation that can be applied to NLME
      models. One variant, where out-of-sample predictions are based on post hoc
      estimates of the random effects, can be used to select the overall structural
      model. Another variant, where cross-validation seeks to minimize the estimated
      random effects rather than the estimated residuals, can be used to select
      covariates to include in the model. We show that these methods produce accurate
      results in a variety of simulated data sets and apply them to two publicly
      available population pharmacokinetic data sets.

PMID- 23532512
TI  - FRET-based imaging of transbilayer movement of pepducin in living cells by novel
      intracellular bioreductively activatable fluorescent probes.
AB  - To elucidate the mechanisms of direct transmembrane penetration of pepducins,
      which are artificial lipopeptide G protein-coupled receptor (GPCR) modulators, we
      developed two types of FRET-based probes, Pep13-FL-SS-Dab (13) targeting the
      inner leaflet of the lipid bilayer and Pep13-Dab-SS-FL (14) targeting the
      cytosol, respectively. They are composed of a pepducin moiety and a fluorescent
      switch component consisting of 5(6)-carboxyfluorescein (FAM) as a fluorophore and
      dabcyl as a quencher connected through disulfide bond linkage. When they are
      internalized into the cytosol, intracellular glutathione can cleave the disulfide
      bond to release the quencher, which results in a turn-on fluorescence signal.
      Using these probes, we performed live cell imaging of transbilayer movements of
      pepducins on MCF-7 cells for the first time. The results suggested that the lipid
      moiety of the probes facilitated pepducin flipping across and tethering to the
      membrane. The present study raises the possibility of applying the probe
      architecture for direct intracellular drug delivery.

PMID- 23532513
TI  - Sophorolipid production from delignined corncob residue by Wickerhamiella
      domercqiae var. sophorolipid CGMCC 1576 and Cryptococcus curvatus ATCC 96219.
AB  - Delignined corncob residue hydrolysate (DCCRH) and detoxified DCCRH were used for
      single cell oil (SCO) and single cell protein (SCP) production of Cryptococcus
      curvatus ATCC 96219 and for sophorolipid (SL) production of Wickerhamiella
      domercqiae var. sophorolipid CGMCC 1576. Both C. curvatus and W. domercqiae could
      utilize glucose in DCCRH to grow and accumulate lipids or particle-shaped SLs.
      DCCRH detoxification by activated carbon adsorption not only improved cell growth
      and lipid accumulation of C. curvatus but also increased SL production and
      proportion of lactonic SL in total SL. A total biomass of 17.36 g/l with a lipid
      content of 44.36 % could be achieved after cultivation of C. curvatus on the
      detoxified DCCRH. The predominant fatty acids of the produced SCO were oleic,
      stearic, and palmitic acids (27.2, 20.5, and 15.7 %, respectively). When W.
      domercqiae cells were cultivated on DCCRH and SCO, total SL production of 39.08
      g/l (DCCRH + SCO) and 42.06 g/l (detoxified DCCRH + SCO) were obtained.
      Furthermore, when cell lysate of C. curvatus, oleic acid, and DCCRH/detoxified
      DCCRH was used as nitrogen and carbon sources, total SL production reached 37.19
      g/l and 48.97 g/l, respectively. These results demonstrated that renewable DCCRH
      can be utilized for the production of high-value SCO and SLs. 

PMID- 23532514
TI  - Novel TTC19 mutation in a family with severe psychiatric manifestations and
      complex III deficiency.
AB  - Complex III of the mitochondrial respiratory chain (CIII) catalyzes transfer of
      electrons from reduced coenzyme Q to cytochrome c. Low biochemical activity of
      CIII is not a frequent etiology in disorders of oxidative metabolism and is
      genetically heterogeneous. Recently, mutations in the human tetratricopeptide 19
      gene (TTC19) have been involved in the etiology of CIII deficiency through
      impaired assembly of the holocomplex. We investigated a consanguineous Portuguese
      family where four siblings had reduced enzymatic activity of CIII in muscle and
      harbored a novel homozygous mutation in TTC19. The clinical phenotype in the four
      sibs was consistent with severe olivo-ponto-cerebellar atrophy, although their
      age at onset differed slightly. Interestingly, three patients also presented
      progressive psychosis. The mutation resulted in almost complete absence of TTC19
      protein, defective assembly of CIII in muscle, and enhanced production of
      reactive oxygen species in cultured skin fibroblasts. Our findings add to the
      array of mutations in TTC19, corroborate the notion of genotype/phenotype
      variability in mitochondrial encephalomyopathies even within a single family, and
      indicate that psychiatric manifestations are a further presentation of low CIII.

PMID- 23532515
TI  - [Grafts with microvascular anastomosis. Their use in the head and neck region
      following radiotherapy and vessel depletion].
AB  - Surgical tumor removal is often the treatment of choice in patients with head and
      neck squamous cell carcinoma. Depending on the extent of tumor resection, large
      defects are often produced in the individual head and neck regions, necessitating
      reconstructive surgery to avoid further functional impairment. In principle, this
      decision depends on the size and location of the defect, the aesthetic importance
      of the region and the functional significance of the area to be replaced.
      Reconstructive free flap procedures in patients who have undergone radiotherapy
      or exhibit vessel depletion in the neck due to multiple previous surgical
      interventions are particularly challenging. In order to ensure the best possible
      outcomes of surgical oncology therapies under difficult circumstances, this paper
      discusses the important factors and variables that can increase the success rate
      of microvascular grafts in irradiated or multiply resected patients. 

PMID- 23532516
TI  - [The simultaneous appearance of three uncommon tumours].
AB  - A 70-year-old woman presented with nasal obstruction and pain projecting onto the
      left cheek. The face seemed asymmetric including exophthalmus on the right side.
      Nasal endoscopic inspection revealed a sarcomatous tumor located on the middle
      turbinate. The CT showed that the tumor filled the left maxillary sinus
      completely and had eroded the maxillary bone. In addition, a round, sharply
      defined intraorbital neoplasm on the right side was identified in the contrast
      enhanced MRI. Histological examination of the extirpated intraorbital tumour
      showed a neurilemmoma. A tissue biopsy of the intranasal tumour falsely suggested
      an intestinal adenocarcinoma. Multiple neoplasms suspicious of disseminated lung
      metastases were detected in the CT of the thorax. One round lesion removed by
      thoracoscopy revealed a carcinoid. The intranasal tumour was excised completely
      and the histology proved beyond doubt an inverted papilloma. 

PMID- 23532517
TI  - Neutrophils in local and systemic antibody-dependent inflammatory and
      anaphylactic reactions.
AB  - Neutrophils are notorious for their efficacy in microbial killing. Various
      mechanisms, such as phagocytosis, production of ROS, cytokines/chemokines and
      lipid mediators, degranulation of antimicrobials and enzymes, as well as NETosis
      contribute to this capacity. However, every incidence of neutrophil activation
      bears a risk to cause damage to the host. Several distinct steps, i.e., adhesion
      to endothelial cells, transmigration, chemotaxis, cytokine stimulation, and TLR
      signaling, are thought to control the extent of neutrophil activation. In the
      absence of a microbial stimulus, other pathways can induce neutrophil activation,
      among which FcR-induced activation when neutrophils encounter ICs. In these
      situations (inflammation, autoimmunity, allergy), neutrophils may act as primary
      or secondary effectors of immune reactions. In the presence of circulating ICs,
      neutrophils can indeed get stimulated directly in the bloodstream and trigger an
      immune response. Upon deposition of antibody complexes inside of tissues,
      neutrophils are first recruited and primed before being highly activated to
      amplify the ongoing inflammation. This review focuses on the engagement,
      activation, and responses of neutrophils to antibody ICs, inside of tissues or in
      the vasculature. 

PMID- 23532518
TI  - CCL26/eotaxin-3 is more effective to induce the migration of eosinophils of
      asthmatics than CCL11/eotaxin-1 and CCL24/eotaxin-2.
AB  - CCL11, CCL24, and CCL26 are chemokines involved in the recruitment of eosinophils
      into tissues and mainly activate CCR3. Whereas the genomic or pharmacological
      inhibition of CCR3 prevents the development of experimental asthma in rodents, it
      only impairs the recruitment of eosinophils by ~40% in humans. As humans, but not
      rodents, express CCL26, we investigated the impact of CCL11, CCL24, and CCL26 on
      human eosinophils recruitment and evaluated the involvement of CCR3. The
      migration of eosinophils of healthy volunteers was similar for the three
      eotaxins. Eosinophils of mild asthmatics had a greater response to CCL11 and a
      much greater response to CCL26. Whereas all eotaxins induced the migration of
      eosinophil of asthmatics from 0 to 6 h, CCL26 triggered a second phase of
      migration between 12 and 18 h. Given that the CCR3 antagonists SB 328437 and SB
      297006 inhibited the 5-oxo-eicosatetraenoate-induced migration of eosinophils and
      that the CCR3 antagonist UCB 35625 was not specific for CCR3, CCR3 blockade was
      performed with the CCR3 mAb. This antibody completely blocked the effect of all
      eotaxins on eosinophils of healthy subjects and the effect of CCL24 on the
      eosinophils of asthmatics. Interestingly, CCR3 blockade did not affect the second
      migration phase induced by CCL26 on eosinophils of asthmatics. In conclusion,
      CCL26 is a more effective chemoattractant than CCL11 and CCL24 for eosinophils of
      asthmatics. The mechanism of this greater efficiency is not yet defined. However,
      these results suggest that CCL26 may play a unique and important role in the
      recruitment of eosinophils in persistent asthma. 

PMID- 23532519
TI  - Screening of RB1 alterations in Brazilian patients with retinoblastoma and
      relatives with retinoma: phenotypic and genotypic associations.
AB  - PURPOSE: To identify constitutional alterations of the retinoblastoma 1 gene
      (RB1) in two cohorts of Brazilian patients with retinoblastoma and to analyze
      genotype-phenotype associations. METHODS: Molecular screening was carried out by
      direct sequencing of the 27 RB1 exons and flanking regions in blood DNA of 71
      patients with retinoblastoma and 4 relatives with retinoma, and with multiplex
      ligation-dependent probe amplification (MLPA) in 21 patients. The presumed impact
      of nucleotide substitutions on the structure of the retinoblastoma protein (pRB)
      was predicted by Polymorphism Phenotyping-2 (PolyPhen-2). Kaplan-Meier and log
      rank test were used for estimating 60-month survival rates. RESULTS: One hundred
      two nucleotide substitutions were detected, 92 substitutions in 59 patients with
      retinoblastoma and 10 substitutions in 4 individuals with retinoma. Eight
      substitutions were novel. The majority of substitutions were intronic (86.2%).
      More than one substitution was present in 37.3% of patients. Twenty-one
      duplications and 11 deletions were found in 12 patients; some of which with both
      types of alterations. Duplications/deletions were found in four patients lacking
      constitutional alterations when analyzed by sequencing, and in eight patients
      carrying one or more polymorphic intronic substitutions. The global 60-month
      survival rate in patients was 91.8% (Confidence Interval95% = 85.0 - 99.1).
      Significant, lower survival rates were found in extraocular presentation (81.0%)
      versus intraocular tumors (P = 0.014), first enucleation after 1 month following
      diagnosis (80.9%) versus earlier first enucleation (P = 0.020), and relapse
      (100.0%) versus absence of relapse (P = 0.0005). CONCLUSIONS: Fifteen
      substitutions (4 intronic and 11 exonic) were identified as probably or likely
      pathogenic. Four of these 11 exonic substitutions were novel. Survival rates,
      however, were not affected by presence of these probably or likely pathogenic
      alterations, most of which not found in patients with retinoblastoma from other
      Latin American countries. These differences might be related to the different
      ethnic composition of the Latin American cohorts. Portuguese Abstract.

PMID- 23532521
TI  - Mature dendritic cell suppression by IL-1 receptor antagonist on retinal pigment
      epithelium cells.
AB  - PURPOSE: To determine whether retinal pigment epithelial (RPE) cells can inhibit
      mature dendritic cells (mDCs). METHODS: Cultured RPE cells were established from
      C57BL/6 mice. DCs were established from bone marrow cells of normal mice, and
      mDCc were induced by culture in medium containing granulocyte macrophage-colony
      stimulating factor (GM-CSF) and IL-4 in the presence of lipopolysaccharide and
      TNF-alpha. Activation of mDCs was assessed by a proliferation assay and ELISA to
      measure the production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL
      12p40). Expression of major histocompatibility complex (MHC) class II, CD11c, and
      costimulatory molecules such as CD80, CD86, programmed cell death 1 ligand 1 (PD
      L1), and PD-L2 on mDCs or RPE-exposed mDCs was evaluated by immune staining and
      flow cytometry. Production of IL-1 receptor antagonist (IL-1Ra) by RPE cells was
      evaluated by oligonucleotide microarray or ELISA. Anti-IL-1Ra neutralizing
      antibodies or RPE cells from IL-1Ra knockout donors were used for the assay.
      RESULTS: Cultured RPE cells greatly suppressed the activation of mDCs, especially
      the production of pro-inflammatory cytokines, and the expression of cell-surface
      molecules. Moreover, RPE cells significantly suppressed mixed lymphocyte
      reactions by mDCs. In an examination of immunoregulatory candidate molecules, RPE
      cells expressed much higher levels of IL-1Ra as compared with control cells, and
      RPE cells pretreated with recombinant TNF-alpha and/or IL-1beta produced high
      levels of IL-1Ra. RPE cells in the presence of anti-IL-1Ra antibodies, but not
      other candidate factors, failed to suppress activation by mDCs. In addition, RPE
      cells from IL-1Ra null donors failed to suppress mDC activation. CONCLUSIONS: Our
      results suggest that ocular resident cells can produce pro-inflammatory cytokine
      antagonist that suppresses antigen-presenting cell activation.

PMID- 23532520
TI  - Antiapoptotic properties of alpha-crystallin-derived peptide chaperones and
      characterization of their uptake transporters in human RPE cells.
AB  - PURPOSE: The chaperone proteins, alpha-crystallins, also possess antiapoptotic
      properties. The purpose of the present study was to investigate whether 19 to 20
      mer alpha-crystallin-derived mini-chaperone peptides (alpha-crystallin mini
      chaperone) are antiapoptotic, and to identify their putative transporters in
      human fetal RPE (hfRPE) cells. METHODS: Cell death and caspase-3 activation
      induced by oxidative stress were quantified in early passage hfRPE cells in the
      presence of 19 to 20-mer alphaA- or alphaB-crystallin-derived or scrambled
      peptides. Cellular uptake of fluorescein-labeled, alpha-crystallin-derived mini
      peptides and recombinant full-length alphaB-crystallin was determined in
      confluent hfRPE. The entry mechanism in hfRPE cells for alpha-crystallin mini
      peptides was investigated. The protective role of polycaprolactone (PCL)
      nanoparticle encapsulated alphaB-crystallin mini-chaperone peptides from H2O2
      induced cell death was studied. RESULTS: Primary hfRPE cells exposed to oxidative
      stress and either alphaA- or alphaB-crystallin mini-chaperones remained viable
      and showed marked inhibition of both cell death and activation of caspase-3.
      Uptake of full-length alphaB-crystallin was minimal while a time-dependent uptake
      of alphaB-crystallin-derived peptide was observed. The mini-peptides entered the
      hfRPE cells via the sodium-coupled oligopeptide transporters 1 and 2 (SOPT1,
      SOPT2). PCL nanoparticles containing alphaB-crystallin mini-chaperone were also
      taken up and protected hfRPE from H2O2-induced cell death at significantly lower
      concentrations than free alphaB-crystallin mini-chaperone peptide. CONCLUSIONS:
      alphaA- and alphaB-crystallin mini-chaperones offer protection to hfRPE cells and
      inhibit caspase-3 activation. The oligopeptide transporters SOPT1 and SOPT2
      mediate the uptake of these peptides in RPE cells. Nanodelivery of alphaB
      crystallin-derived mini-chaperone peptide offers an alternative approach for
      protection of hfRPE cells from oxidant injury.

PMID- 23532522
TI  - Retrobulbar structure visualization with enhanced depth imaging optical coherence
      tomography.
AB  - PURPOSE: To assess enhanced depth imaging optical coherence tomography (EDI-OCT)
      visualization of deep posterior pole structures and retrobulbar tissues in myopic
      eyes and evaluate ocular structural elements that influence this capability.
      METHODS: Thirty consecutive myopic eyes (>-6 diopters) from 21 patients were
      enrolled. Exclusion criteria included any pathological condition affecting the
      posterior pole. Patients underwent biometry to assess axial length, and irises
      were classified as darkly or lightly pigmented. EDI-OCT scans were obtained by
      spectral-domain OCT to image posterior pole and retrobulbar structures. Choroidal
      thickness was measured manually, and for eyes in which the sclera was fully
      visible, scleral thickness was also measured manually. The influence of central
      retinal thickness, axial length, refractive error, mean choroidal thickness, mean
      scleral thickness, and iris pigmentation on EDI-OCT visualization of structures
      beyond the choroid was tested. RESULTS: Choroidal thickness was measurable in all
      eyes. In 11 of 30 eyes, the sclera was not completely visible (group 1). In 19
      eyes, the full scleral thickness was measurable (group 2). In seven of the group
      2 eyes, the full sclera was the deepest structure detected. In the remaining 11
      eyes, deeper structures were visible. Choroidal thickness was the only parameter
      that correlated with the ability to visualize the full sclera (P < 0.001) and
      deeper structures (P = 0.044). CONCLUSIONS: The full thickness of the choroid was
      visualized by EDI-OCT in all eyes. Full thicknesses of the sclera and retrobulbar
      structures were not always visible. Choroidal thickness was the only parameter
      that significantly correlated with EDI-OCT visualization of deeper structures.

PMID- 23532523
TI  - Quantitative analysis of tear film fluorescence and discomfort during tear film
      instability and thinning.
AB  - PURPOSE: The purpose of this study was to test the association between tear film
      fluorescence changes during tear break-up (TBU) or thinning and the concurrent
      ocular sensory response. METHODS: Sixteen subjects kept one eye open as long as
      possible (MBI), indicated their discomfort level continuously, and rated ocular
      sensations of irritation, stinging, burning, pricking, and cooling using visual
      analog scales (VAS). Fluorescence of the tear film was quantified by a pixel
      based analysis of the median pixel intensity (PI), TBU, and percentage of dark
      pixels (DarkPix) over time. A cutoff of 5% TBU was used to divide subjects into
      either break-up (BU) or minimal break-up (BUmin) groups. RESULTS: Tear film
      fluorescence decreased (median PI) and the percentage of TBU and DarkPix
      increased in all trials, with the rate significantly greater in the BU than the
      BUmin group (Mann-Whitney U test, P < 0.05). The rate of increasing discomfort
      during trials was highly correlated with the rate of decrease in median PI and
      developing TBU (Spearman's, r >= 0.70). Significant correlations were found
      between corneal fluorescence, MBI, and sensory measures. CONCLUSIONS:
      Concentration quenching of fluorescein dye with tear film thinning best explains
      decreasing tear film fluorescence during trials. This was highly correlated with
      increasing ocular discomfort, suggesting that both tear film thinning and TBU
      stimulate underlying corneal nerves, although TBU produced more rapid
      stimulation. Slow increases in tear film hyperosmolarity may cause the gradual
      increase in discomfort during slow tear film thinning, whereas the sharp
      increases in discomfort during TBU suggest a more complex stimulus.

PMID- 23532524
TI  - Relationship between the second reflective band on optical coherence tomography
      and multifocal electroretinography in age-related macular degeneration.
AB  - PURPOSE: The second hyper-reflective on spectral domain optical coherence
      tomography (SD-OCT) has been suggested to correlate with the photoreceptor inner
      segment ellipsoids (ISe). The purpose of our study was to determine the
      relationship between the intensity of the ISe band and retinal function measured
      by multifocal electroretinography (mfERG) in patients with early age-related
      macular degeneration (AMD). METHODS: A high-resolution horizontal line scan
      through the fovea on SD-OCT and an mfERG recording were performed in one eye of
      29 early AMD and 31 control participants. The relative intensity of the ISe band
      within 1000 MUm of the fovea was quantified using ImageJ. The relationships
      between the relative intensity of the ISe band and the mfERG response parameters
      (P1 amplitude and implicit time) within the three central hexagons along the
      horizontal axis were determined. RESULTS: In normal participants, the relative
      intensity of the ISe band was significantly correlated with age (r = -0.634, P <
      0.001) and also exhibited a topographic variation. On average, the relative
      intensity of the ISe band was significantly lower in patients with early AMD
      (1.77 +/- 0.26) compared to control subjects (1.95 +/- 0.27, P < 0.001) of a
      similar age range. The relative intensity of the ISe band was correlated
      significantly with the mfERG P1 implicit time (r = -0.745, P < 0.001), but not P1
      amplitude (r = 0.144, P = 0.281). CONCLUSIONS: The relative intensity of the ISe
      band reduced with age and further in early AMD. The relative intensity was
      significantly correlated with mfERG P1 implicit time.

PMID- 23532525
TI  - Reflectance speckle of retinal nerve fiber layer reveals axonal activity.
AB  - PURPOSE: This study investigated the retinal nerve fiber layer (RNFL) reflectance
      speckle and tested the hypothesis that temporal change of RNFL speckle reveals
      axonal dynamic activity. METHODS: RNFL reflectance speckle of isolated rat
      retinas was studied with monochromatic illumination. A series of reflectance
      images was collected every 5 seconds for approximately 15 minutes. Correlation
      coefficients (CC) of selected areas between a reference and subsequent images
      were calculated and plotted as a function of the time intervals between images.
      An exponential function fit to the time course was used to evaluate temporal
      change of speckle pattern. To relate temporal change of speckle to axonal
      activity, in vitro living retina perfused at a normal (34 degrees C) and a lower
      (24 degrees C) temperature, paraformaldehyde-fixed retina, and retina treated
      with microtubule depolymerization were used. RESULTS: RNFL reflectance was not
      uniform; rather nerve fiber bundles had a speckled texture that changed with
      time. In normally perfused retina, the time constant of the CC change was 0.56 +/
      0.26 minutes. In retinas treated with lower temperature and microtubule
      depolymerization, the time constants increased by two to four times, indicating
      that the speckle pattern changed more slowly. The speckled texture in fixed
      retina was stationary. CONCLUSIONS: Fixation stops axonal activity; treatments
      with either lower temperature or microtubule depolymerization are known to
      decrease axonal transport. The results obtained in this study suggest that
      temporal change of RNFL speckle reveals structural change due to axonal activity.
      Assessment of RNFL reflectance speckle may offer a new means of evaluating axonal
      function.

PMID- 23532526
TI  - Treatment of acute posterior uveitis in a porcine model by injection of
      triamcinolone acetonide into the suprachoroidal space using microneedles.
AB  - PURPOSE: To evaluate the effect of triamcinolone acetonide (TA) administered into
      the suprachoroidal space (SCS) using a microneedle and compare it with
      intravitreal (IVT) TA injections in a porcine model of acute posterior segment
      inflammation. MATERIALS: An IVT injection of balanced salt solution (BSS) or
      lipopolysaccharide (LPS) was followed 24 hours later with an injection of 0.2 mg
      or 2.0 mg of TA into the SCS or IVT. The SCS was accessed using microneedles in a
      minimally invasive procedure. Ocular inflammatory scores and IOP measurements
      were collected daily, whereas electroretinography, optical coherence tomography,
      and wide-field ocular fundus photography was performed on -1, 0, and 3 days after
      treatment. Aqueous and vitreous humor cell counts and protein levels and
      histopathology were also compared. RESULTS: Delivery of TA to the SCS using
      microneedles was simple, effective, and not associated with adverse effects or
      toxicity. SCS injection of low (0.2 mg) and high doses (2.0 mg) of TA was as
      effective in reducing acute inflammation in the ocular posterior segment as high
      dose IVT injection. Low-dose SCS TA was also effective in reducing inflammation;
      however, low-dose IVT TA was not. CONCLUSIONS: Results from this study suggest
      that 0.2 mg and 2.0 mg of SCS TA was as effective in reducing inflammation as 2.0
      mg IVT TA injection in a model of acute posterior segment inflammation. There
      were no adverse effects, increased IOP, or evidence of procedural or drug
      toxicity following injection of TA into the SCS in porcine eyes.

PMID- 23532527
TI  - Spectrophotometric retinal oximetry in pigs.
AB  - PURPOSE: To assess the validity of spectrophotometric retinal oximetry by
      comparison to blood gas analysis and intravitreal measurements of partial
      pressure of oxygen (pO(2)). METHODS: Female domestic pigs were used for all
      experiments (n = 8). Oxygen fraction in inspired air was changed using a mixture
      of room air, pure oxygen, and pure nitrogen, ranging from 5% to 100% oxygen.
      Femoral arterial blood gas analysis and retinal oximetry were performed at each
      level of inspiratory oxygen fraction. Retinal oximetry was performed using a
      commercial instrument, the Oxymap Retinal Oximeter T1. The device simultaneously
      acquires images at two wavelengths (570 nm and 600 nm), and specialized software
      automatically detects retinal blood vessels. In three pigs, invasive pO(2)
      measurements were performed after the initial noninvasive measurements. RESULTS:
      Comparison of femoral arterial oxygen saturation and the optical density ratio
      over retinal arteries revealed an approximately linear relationship (R(2) = 0.74,
      P = 3.4 * 10(-9)). In order to test the validity of applying the arterial
      calibration to veins, we compared noninvasive oximetry measurements to invasive
      pO2 measurements in three pigs. This relationship was approximately linear (R(2)
      = 0.45, P = 0.04). CONCLUSIONS: Noninvasive spectrophotometric oximetry is
      sensitive to changes in oxygen saturation in pigs and correlated with
      intravitreal pO(2) measurements and with femoral artery pO(2). Pigs present a
      higher intraindividual variability in retinal oxygen saturation and a lower
      overall saturation than do humans. The difference between porcine and human eyes
      makes direct comparisons of measurements difficult.

PMID- 23532528
TI  - Transcription factors Runx1 to 3 are expressed in the lacrimal gland epithelium
      and are involved in regulation of gland morphogenesis and regeneration.
AB  - PURPOSE: Lacrimal gland (LG) morphogenesis and repair are regulated by a complex
      interplay of intrinsic factors (e.g., transcription factors) and extrinsic
      signals (e.g., soluble growth/signaling factors). Many of these interconnections
      remain poorly characterized. Runt-related (Runx) factors belong to a small family
      of heterodimeric transcription factors known to regulate lineage-specific
      proliferation and differentiation of stem cells. The purpose of this study was to
      define the expression pattern and the role of Runx proteins in LG development and
      regeneration. METHODS: Expression of epithelial-restricted transcription factors
      in murine LG was examined using immunostaining, qRT-PCR, and RT(2)Profiler PCR
      microarrays. The role of Runx transcription factors in LG morphogenesis was
      studied using siRNA and ex vivo LG cultures. Expression of Runx transcription
      factors during LG regeneration was assessed using in vivo model of LG
      regeneration. RESULTS: We found that Runx factors are expressed in the epithelial
      compartment of the LG; in particular, Runx1 was restricted to the epithelium with
      highest level of expression in ductal and centroacinar cells. Downregulation of
      Runx1 to 3 expression using Runx-specific siRNAs abolished LG growth and
      branching and our data suggest that Runx1, 2, and 3 are partially redundant in LG
      development. In siRNA-treated LG, reduction of branching correlated with
      reduction of epithelial proliferation, as well as expression of cyclin D1 and the
      putative epithelial progenitor cell marker cytokeratin-5. Runx1, Runx3, and
      cytokeratin-5 expression increased significantly in regenerating LG and there was
      modest increase in Runx2 expression during LG differentiation. CONCLUSIONS: Runx1
      and 2 are new markers of the LG epithelial lineage and Runx factors are important
      for normal LG morphogenesis and regeneration.

PMID- 23532529
TI  - Comparison of different spectral domain OCT scanning protocols for diagnosing
      preperimetric glaucoma.
AB  - PURPOSE: To compare the ability of spectral-domain optical coherence tomography
      (SDOCT) retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular
      measurements to detect preperimetric glaucomatous damage. METHODS: The study
      included 142 eyes from 91 patients suspected of having the disease based on the
      appearance of the optic disc. All eyes had normal visual fields before the
      imaging session. Forty-eight eyes with progressive glaucomatous damage were
      included in the preperimetric glaucoma group. Ninety-four eyes without any
      evidence of progressive glaucomatous damage and followed untreated for 12.8 +/-
      3.6 years were used as controls. Areas under the receiver operating
      characteristic curves (AUC) were calculated to summarize diagnostic accuracies of
      the parameters. RESULTS: The three RNFL parameters with the largest AUCs were
      average RNFL thickness (0.89 +/- 0.03), inferior hemisphere average thickness
      (0.87 +/- 0.03), and inferior quadrant average thickness (0.85 +/- 0.03). The
      three ONH parameters with the largest AUCs were vertical cup-to-disc ratio (0.74
      +/- 0.04), rim area (0.72 +/- 0.05), and rim volume (0.72 +/- 0.05). The three
      macular parameters with the largest AUCs were GCC average thickness (0.79 +/-
      0.04), GCC inferior thickness (0.79 +/- 0.05), and GCC superior thickness (0.76
      +/- 0.05). Average RNFL thickness performed better than vertical cup-to-disc
      ratio (0.89 vs. 0.74; P = 0.007) and GCC average thickness (0.89 vs. 0.79; P =
      0.015). CONCLUSIONS: SDOCT RNFL measurements performed better than ONH and
      macular measurements for detecting preperimetric glaucomatous damage in a cohort
      of glaucoma suspects. (ClinicalTrials.gov number, NCT00221897.).

PMID- 23532530
TI  - Novel oral anti-obesity agents: new perspectives with lorcaserin?

PMID- 23532531
TI  - Common variants at 8q24 are associated with prostate cancer risk in Serbian
      population.
AB  - Previous studies have shown correlation between single nucleotide polymorphisms
      (SNPs) at 8q24 and prostate cancer (PCa) risk. This study aimed to evaluate
      possible association between genotypes and alleles of 8q24 polymorphisms
      (rs1447295, rs4242382, rs6983267, rs7017300, and rs7837688) and PCa risk and
      progression. 150 patients with PCa, 150 patients with benign prostatic
      hyperplasia (BPH), and 100 healthy controls selected from the general population
      were recruited for this study. SNPs were genotyped by using PCR-RFLP analysis.
      There was a significant positive association between the A allele of the SNP
      rs4242382 and PCa risk [PCa vs. BPH comparison, P = 0.014 for the best-fitting
      dominant model; odds ratio (OR) =1.98; 95 % confidence interval (95%CI) 1.14
      3.43]. We found evidence (P = 0.0064) of association between PCa risk and
      rs7017300 (heterozygote OR = 1.60; 95%CI 0.95-2.69) when comparing genotype
      distributions in PCa and BPH patients. The association between T allele rs7837688
      and PCa risk was determined in PCa vs. BPH comparison with the best-fitting model
      of inheritance being log-additive (P = 0.0033; OR = 2.14, 95%CI 1.27-3.61). Odds
      ratio for carriers of rs6983267 TT genotype under recessive model of association
      with PCa was found to be 0.36 (PCa vs. control comparison, P = 0.0029; 95%CI 0.19
      0.71). For rs1447295, deviation from Hardy-Weinberg equilibrium was observed in
      BPH patients and controls. We found no association between parameters of PCa
      progression and five 8q24 SNPs. Locus 8q24 harbors genetic variants associated
      with PCa risk in Serbian population. 

PMID- 23532532
TI  - Investigating the fate of iodinated X-ray contrast media iohexol and diatrizoate
      during microbial degradation in an MBBR system treating urban wastewater.
AB  - The capability of a moving bed biofilm reactor (MBBR) to remove the iodinated
      contrast media (ICM) iohexol (IOX) and diatrizoate (DTZ) from municipal
      wastewater was studied. A selected number of clones of microorganisms present in
      the biofilm were identified. Biotransformation products were tentatively
      identified and the toxicity of the treated effluent was assessed. Microbial
      samples were DNA-sequenced and subjected to phylogenetic analysis in order to
      confirm the identity of the microorganisms present and determine the microbial
      diversity. The analysis demonstrated that the wastewater was populated by a
      bacterial consortium related to different members of Proteobacteria, Firmicutes,
      and Nitrisporae. The optimum removal values of the ICM achieved were 79 % for IOX
      and 73 % for DTZ, whereas 13 biotransformation products for IOX and 14 for DTZ
      were identified. Their determination was performed using ultra-performance liquid
      chromatography-tandem mass spectrometry. The toxicity of the treated effluent
      tested to Daphnia magna showed no statistical difference compared to that without
      the addition of the two ICM. The MBBR was proven to be a technology able to
      remove a significant percentage of the two ICM from urban wastewater without the
      formation of toxic biodegradation products. A large number of biotransformation
      products was found to be formed. Even though the amount of clones sequenced in
      this study does not reveal the entire bacterial diversity present, it provides an
      indication of the predominating phylotypes inhabiting the study site.

PMID- 23532533
TI  - PFAS profiles in three North Sea top predators: metabolic differences among
      species?
AB  - Profiles of seven compounds of perfluoro-alkyl substances (PFASs) were compared
      among three species of top predators from the Danish North Sea: the white-beaked
      dolphin (Lagenorhynchus albirostris), the harbor porpoise (Phocoena phocoena),
      and the harbor seal (Phoca vitulina). The seals had higher total burdens (757.8
      ng g(-1) ww) than the dolphins (439.9 ng g(-1) ww) and the porpoises (355.8 ng g(
      1) ww), probably a reflection of feeding closer to the shore and thus
      contamination sources. The most striking difference among the species was the
      relative contribution of perfluorooctanesulfonamide (PFOSA) to the profiles; the
      seals (0.1%) had much lower levels than porpoises (8.3%) and dolphins (26.0%). In
      combination with the values obtained from the literature, this result indicates
      that Carnivora species including Pinnipedia have a much higher capacity of
      transforming PFOSA to perfluorooctane sulfonic acid (PFOS) than cetacean species.
      Another notable difference among the species was that the two smaller species
      (seals and porpoises) with supposedly higher metabolic rates had lower
      concentrations of the perfluorinated carboxylic acids, which are generally more
      easily excreted than perfluorinated sulfonamides. Species-specific
      characteristics should be recognized when PFAS contamination in marine mammals is
      investigated, for example, several previous studies of PFASs in cetaceans have
      not quantified PFOSA.

PMID- 23532534
TI  - Endocrine disruptors compounds, pharmaceuticals and personal care products in
      urban wastewater: implications for agricultural reuse and their removal by
      adsorption process.
AB  - In the last years, a lot of emerging contaminants, such as, endocrine disruptors
      compounds (EDCs), pharmaceuticals, and personal care products (PPCPs) have been
      detected in wastewater. Because of their toxicity and possible adverse effects on
      the environment and humans, their release from urban wastewater treatment plants
      (UWWTPs) effluents should be minimized, particularly when a wastewater reuse for
      crops irrigation is expected. Many processes have been investigated for advanced
      treatment of UWWTP effluents as well as for emerging contaminant degradation;
      among these, adsorption process was successfully used to remove EDCs and PPCPs
      from wastewater. This article shortly reviews EDCs and PPCPs removal from UWWTP
      effluents by adsorption process using conventional and non-conventional
      adsorbents. The fate of EDCs and PPCPs in UWWTPs and the implications for
      agricultural wastewater reuse has been addressed too. In spite of the adsorption
      process looking to be a valuable alternative to other advanced technologies for
      the removal of emerging contaminants from wastewater, some gaps still remain to
      evaluate the actual feasibility at full scale. However, according to a few
      studies available in scientific literature on the use of both powdered activated
      carbon and granular activated carbon at full scale, adsorption process by
      activated carbon is a promising, potentially effective, and economically feasible
      solution for producing safe wastewater for agricultural reuse.

PMID- 23532535
TI  - Is the evaluation of "traditional" physicochemical parameters sufficient to
      explain the potential toxicity of the treated wastewater at sewage treatment
      plants?
AB  - Water scarcity is one of the most important environmental and public health
      problems of our century. Treated wastewater reuse seems to be the most attractive
      option for the enhancement of water resources. However, the lack of uniform
      guidelines at European and/or Mediterranean level leaves room for application of
      varying guidelines and regulations, usually not based on risk assessment towards
      humans and the environment. The benefits of complementing the physicochemical
      evaluation of wastewater with a biological one are demonstrated in the present
      study using Cyprus, a country with extended water reuse applications, as an
      example. Four organisms from different trophic levels were used for the
      biological assessment of the wastewater, namely, Pseudokirchneriella subcapitata,
      Daphnia magna, Artemia salina and Vibrio fischeri. The physicochemical assessment
      of wastewater based on "traditional" chemical parameters indicated that the
      quality of the wastewater complies with the limits set by the relevant national
      guidelines for disposal. The ecotoxicological assessment, however, indicated the
      presence of toxicity throughout the sampling periods and most importantly an
      increase of the toxicity of the treated wastewater during summer compared to
      winter. The resulting poor correlation between the physicochemical and biological
      assessments demonstrates that the two assessments are necessary and should be
      performed in parallel in order to be able to obtain concrete results on the
      overall quality of the treated effluent. Moreover, a hazard classification scheme
      for wastewater is proposed, which can enable the comparison of the data sets of
      the various parameters deriving from the biological assessment in a comprehensive
      way.

PMID- 23532536
TI  - The effects of 3,3',4,4'-tetrabromobiphenyl on rats fed diets containing a
      constant level of copper and varying levels of molybdenum.
AB  - Copper (Cu) metabolism is altered in rats fed diets high in molybdenum (Mo) and
      low in Cu. This 10-week study was carried out to examine the effects of
      supplemental Mo (7.5-240 MUg/g diet) on male Sprague-Dawley rats fed diets
      adequate in Cu (5 MUg/g diet) and to determine the susceptibility of Mo-treated
      animals to the environmental pollutant 3,3',4,4'-tetrabromobiphenyl (TBB). After
      7 weeks of dietary treatment, half of the rats in each group received a single IP
      injection of TBB (150 MUM/kg bw), while the other half received the corn oil
      vehicle. Rats sacrificed at 10 weeks showed no effects of Mo on growth, feed
      efficiency, or selected organ or tissue weights. Dose-dependent effects on plasma
      Mo (0-5.1 MUg/mL), plasma Cu (0.95-0.20 MUg/mL), and bone Cu (3.4-10 MUg/g) in
      control through the high dose were found. Cu sequestration in the bone of Mo
      treated rats is a new finding. TBB treatment resulted in dramatic weight loss and
      loss of absolute organ mass. Relative organ weights were increased, except for
      the thymus. TBB altered the concentrations of certain amino acids. Compared to
      control rats, this polybrominated biphenyl congener significantly decreased
      plasma Cu and ceruloplasmin at higher concentrations of dietary Mo and promoted
      the process of plasma Cu decrease by Mo, suggesting a combined effect.

PMID- 23532537
TI  - Validation of the species sensitivity distribution in retrospective risk
      assessment of herbicides at the river basin scale-the Scheldt river basin case
      study.
AB  - Species sensitivity distribution (SSD) is commonly used in prospective risk
      assessment to derive predicted no-effect concentrations, toxicity exposure
      ratios, and environmental quality standards for individual chemicals such as
      pesticides. The application of SSD in the retrospective risk assessment of
      chemical mixtures at the river basin scale (i.e., the estimation of "multiple
      substance potentially affected fractions" [msPAFs]) has been suggested, but
      detailed critical assessment of such an application is missing. The present study
      investigated the impact of different data validation approaches in a
      retrospective model case study focused on seven herbicides monitored at the
      Scheldt river basin (Belgium) between 1998 and 2009. The study demonstrated the
      successful application of the SSD approach. Relatively high impacts of herbicides
      on aquatic primary producers were predicted. Often, up to 40 % of the primary
      producer communities were affected, as predicted by chronic msPAF, and in some
      cases, the predicted impacts were even more pronounced. The risks posed by the
      studied herbicides decreased during the 1998-2009 period, along with decreasing
      concentrations of highly toxic pesticides such as simazine or isoproturon.
      Various data validation approaches (the removal of duplicate values and outliers,
      the testing of different exposure durations and purities of studied herbicides,
      etc.) substantially affected SSD at the level of individual studied compounds.
      However, the time-consuming validation procedures had only a minor impact on the
      outcomes of the retrospective risk assessment of herbicide mixtures at the river
      basin scale. Selection of the appropriate taxonomic group for SSD calculation and
      selection of the species-specific endpoint (i.e., the most sensitive or average
      value per species) were the most critical steps affecting the final risk values
      predicted. The present validation study provides a methodological basis for the
      practical use of SSD in the retrospective risk assessment of chemical mixtures. 

PMID- 23532538
TI  - Intake of specific fruits and vegetables in relation to risk of estrogen receptor
      negative breast cancer among postmenopausal women.
AB  - In previous studies of postmenopausal women, overall intake of fruits and
      vegetables groups has been inversely associated with estrogen receptor-negative
      (ER-) breast cancer. In this analysis, we prospectively examined the associations
      of specific fruits and vegetables with risk of ER- postmenopausal breast cancer
      among 75,929 women aged 38-63 years at baseline and followed for up to 24 years.
      Dietary data were collected seven times during this period. Cox proportional
      hazard models were used, adjusting for potential confounders, including a
      modified Alternate Mediterranean Diet score. We ascertained 792 incident cases of
      ER- postmenopausal breast cancer. The multivariate relative risk (RR) for every 2
      servings/week consumption for total berries was 0.82 (95 % CI = 0.71-0.96, p =
      0.01), and the RR for women who consumed at least one serving of blueberries a
      week was 0.69 (95 % CI = 0.50-0.95, p = 0.02) compared with non-consumers. Also,
      the RR for consuming at least 2 servings of peaches/nectarines per week was 0.59
      (95 % CI = 0.37-0.93, p = 0.02). Risk of ER- breast cancer was not associated
      with intakes of other specific fruits or vegetables. In conclusion, higher intake
      of berries and peaches was associated with lower risk of ER- breast cancer among
      postmenopausal women. These results are considered exploratory and need to be
      confirmed in further studies.

PMID- 23532539
TI  - The role of intratumoral and systemic IL-6 in breast cancer.
AB  - Chronic low-grade inflammation plays an important role in the pathogenesis of
      several cancer forms including breast cancer. The pleiotropic cytokine IL-6 is a
      key player in systemic inflammation, regulating both the inflammatory response
      and tissue metabolism during acute stimulations. Here, we review the associations
      between IL-6 and breast cancer ranging from in vitro cell culture studies to
      clinical studies, covering the role of IL-6 in controlling breast cancer cell
      growth, regulation of cancer stem cell renewal, as well as breast cancer cell
      migration. Moreover, associations between circulating IL-6 and risk of breast
      cancer, prognosis for patients with prevalent disease, adverse effects and
      interventions to control systemic IL-6 levels in patients are discussed. In
      summary, direct application of IL-6 on breast cancer cells inhibits proliferation
      in estrogen receptor positive cells, while high circulating IL-6 levels are
      correlated with a poor prognosis in breast cancer patients. This discrepancy
      reflects distinct roles of IL-6, with elevated systemic levels being a biomarker
      for tumor burden, physical inactivity, and impaired metabolism, while local
      intratumoral IL-6 signaling is important for controlling breast cancer cell
      growth, metastasis, and self renewal of cancer stem cells.

PMID- 23532540
TI  - Dynamic behavior of rat phosphoenolpyruvate carboxykinase inhibitors: new
      mechanism for enzyme inhibition.
AB  - As an enzyme acting at the junction of gluconeogenic pathway, phosphoenolpyruvate
      carboxykinase (PEPCK) controls substrate flow from Krebs cycle toward glucose
      production. Therefore, it would be advantageous to design effective inhibitors to
      inactivate PEPCK in diabetes mellitus and other abnormalities caused by insulin
      resistance. Such inhibitors may compensate the metabolic consequences of ex
      activity of PEPCK at these conditions. Understanding the mechanism by which
      inhibitors exert their effect on enzyme activity is of great interest for
      designing stronger inhibitors. In the present work, molecular dynamic simulations
      were used to study enzyme-inhibitor interactions. Our results indicate that
      inhibitors of PEPCK with their short chains interact with enzyme active site
      through non-covalent interactions of electrostatic and hydrogen bond nature. The
      data also show that inhibitors neither reach a stable state in their binding site
      nor make static complex with the enzyme active site. Instead, they interact with
      functional groups of active site residues in a dynamic fashion. In this way,
      oxalate and sulfoacetate carrying two negative groups of higher charge density
      and optimum spacing from each other, show more dynamic behavior (lower stability
      in their binding site) and more inhibitory effects than other inhibitors used
      (phosphonoformate, phosphoglycolate and 3-phosphonopropionate).

PMID- 23532542
TI  - Redescription of Neoechinorhynchus (Neoechinorhynchus) golvani Salgado-Maldonado,
      1978 (Acanthocephala: Neoechinorhynchidae) and description of a new species from
      freshwater cichlids (Teleostei: Cichlidae) in Mexico.
AB  - A redescription of Neoechinorhynchus (Neoechinorhynchus) golvani Salgado
      Maldonado (An Inst Biol Univ Nal Auton Mex, Ser Zool 49:35-47, 1978) is
      presented, based on adult specimens collected from the type host Paraneetroplus
      fenestratus from the type location, the Lago de Catemaco lake, Veracruz state,
      Mexico, and its presence is recorded in other cichlids. Detailed studies of N.
      (N.) golvani using light microscopy revealed some taxonomically important,
      previously unreported features, such as the size and shape of fully developed
      adult males and females, and the structure of the eggs. Morphological variability
      in N. (N.) golvani is described. Based on these data, the geographic distribution
      of this species is documented. Neoechinorhynchus (Neoechinorhynchus) panucensis
      n. sp. is described from Herichthys labridens (Pellegrin), Amatitlania
      nigrofasciata (Gunther), and Herichthys cyanoguttatus Baird and Girard (all of
      them Cichlidae), collected in the Rio Atlapexco, a tributary to the upper Rio
      Panuco basin, Hidalgo State, Mexico. This new species stand up alone because of
      its minute proboscis (? 50 * 60, ? 42-55 (48.5) * 48-63 (57.7)) and anterior
      hooks (? 27-30 (28.8) * 3-5 (4), ? 28-32 (30) * 5 (5)). A key to the species of
      Neoechinorhynchus recorded from freshwater fishes in Central and South America is
      included.

PMID- 23532543
TI  - Inhibitory effect of cyclophilin A from the hard tick Haemaphysalis longicornis
      on the growth of Babesia bovis and Babesia bigemina.
AB  - Haemaphysalis longicornis is known as one of the most important ticks
      transmitting Babesia parasites in East Asian countries, including Babesia ovata
      and Babesia gibsoni, as well as Theileria parasites. H. longicornis is not the
      natural vector of Babesia bovis and Babesia bigemina. Vector ticks and
      transmitted parasites are thought to have established unique host-parasite
      interaction for their survival, meaning that vector ticks may have defensive
      molecules for the growth control of parasites in their bodies. However, the
      precise adaptation mechanism of tick-Babesia parasites is still unknown.
      Recently, cyclophilin A (CyPA) was reported to be important for the development
      of Babesia parasites in ticks. To reveal a part of their adaptation mechanism,
      the current study was conducted. An injection of B. bovis-infected RBCs into
      adult female H. longicornis ticks was found to upregulate the expression profiles
      of the gene and protein of CyPA in H. longicornis (HlCyPA). In addition,
      recombinant HlCyPA (rHlCyPA) purified from Escherichia coli exhibited significant
      inhibitory growth effects on B. bovis and B. bigemina cultivated in vitro,
      without any hemolytic effect on bovine RBCs at all concentrations used. In
      conclusion, our results suggest that HlCyPA might play an important role in the
      growth regulation of Babesia parasites in H. longicornis ticks, during natural
      acquisition from an infected host. Furthermore, rHlCyPA may be a potential
      alternative chemotherapeutic agent against babesiosis.

PMID- 23532544
TI  - Survivorship of adult Aedes albopictus (Diptera: Culicidae) feeding on indoor
      ornamental plants with no inflorescence.
AB  - The international trade of lucky bamboo (Dracaena sanderiana [Asparagaceae]) is
      responsible for certain introductions of the exotic species Aedes albopictus
      (Skuse) in California and the Netherlands. Understanding the association of this
      species with lucky bamboo and other ornamental plants is important from a public
      health standpoint. The aim of this study was to investigate the importance of
      indoor ornamental plants as sugar sources for adult A. albopictus. If exposed to
      D. sanderiana, bromeliad (Guzmania spp. hybrid [Bromeliaceae]), Moses-in-the
      cradle (Rhoeo spathacea [Commelinaceae]), 10 % sucrose solution, and a negative
      water control as the only nutrient source, adult female A. albopictus mean
      survival time was 12, 7, 6, 15, and 4 days, respectively. Mean survival times for
      adult males were not significantly different (P > 0.05) from the females and were
      10, 7, 6, 14, and 3 days, respectively. Combined male and female survival times
      were not significantly different on lucky bamboo compared to survival times on a
      10 % sucrose control. Based on our findings, A. albopictus can readily survive
      long enough to complete a gonotrophic cycle and potentially complete the
      extrinsic incubation period for many arboviruses when only provided access to
      lucky bamboo plants or possibly other common ornamentals. Vector control
      professionals should be aware of potential in-home infestations and public health
      concerns associated with mosquito breeding and plant tissue feeding on ornamental
      plants.

PMID- 23532545
TI  - Substrate scope and synthetic applications of the enantioselective reduction of
      alpha-alkyl-beta-arylenones mediated by Old Yellow Enzymes.
AB  - The ene-reductases mediated bioreduction of a selection of open-chain alpha-alkyl
      beta-aryl enones afforded the corresponding saturated alpha-chiral ketones in
      high yield and optical purity in several cases. The stereo-electronic
      requirements of the reaction have been investigated, considering the nature and
      location of substituents on the aromatic ring as well as the steric hindrance at
      the alpha-position and adjacent to the carbonyl functionality. The general
      considerations drawn allow us to guide the design of alpha,beta-unsaturated
      ketones to be employed as substrates of ene-reductases in future preparative
      applications. An interesting case of orthogonality between enzyme-based and
      substrate-based stereocontrol within the highly homologous ene-reductases from
      Saccharomyces species (OYE1-3) has been reported and rationalized with the help
      of computational docking studies. Furthermore, to demonstrate the synthetic
      versatility of the reaction, the key chiral precursors of biologically active
      compounds such as (2'R)-stenusines and (S)-iopanoic acid were obtained. The very
      robust protocol allowed us to run the reactions on preparative scale in
      quantitative yields, with a simple work-up and no chromatographic purification
      steps.

PMID- 23532546
TI  - Predicting ectotherm disease vector spread--benefits from multidisciplinary
      approaches and directions forward.
AB  - The occurrence of ectotherm disease vectors outside of their previous
      distribution area and the emergence of vector-borne diseases can be increasingly
      observed at a global scale and are accompanied by a growing number of studies
      which investigate the vast range of determining factors and their causal links.
      Consequently, a broad span of scientific disciplines is involved in tackling
      these complex phenomena. First, we evaluate the citation behaviour of relevant
      scientific literature in order to clarify the question "do scientists consider
      results of other disciplines to extend their expertise?" We then highlight
      emerging tools and concepts useful for risk assessment. Correlative models
      (regression-based, machine-learning and profile techniques), mechanistic models
      (basic reproduction number R0) and methods of spatial regression, interaction and
      interpolation are described. We discuss further steps towards multidisciplinary
      approaches regarding new tools and emerging concepts to combine existing
      approaches such as Bayesian geostatistical modelling, mechanistic models which
      avoid the need for parameter fitting, joined correlative and mechanistic models,
      multi-criteria decision analysis and geographic profiling. We take the quality of
      both occurrence data for vector, host and disease cases, and data of the
      predictor variables into consideration as both determine the accuracy of risk
      area identification. Finally, we underline the importance of multidisciplinary
      research approaches. Even if the establishment of communication networks between
      scientific disciplines and the share of specific methods is time consuming, it
      promises new insights for the surveillance and control of vector-borne diseases
      worldwide.

PMID- 23532547
TI  - Cognitive correlates of negative symptoms in behavioral variant frontotemporal
      dementia: implications for the frontal lobe syndrome.
AB  - Although both behavioral disturbances and executive impairments of patients with
      the behavioral variant frontotemporal dementia (bvFTD) seem to depend on early
      neurodegenerative damages to the prefrontal cortex, the relationship between
      these two distinct clinical features has been only partially established and
      represents the focus of the current preliminary neuropsychological study. Ten
      subsequent bvFTD patients underwent a neuropsychiatric assessment with the
      Frontal Behavior Inventory and a neuropsychological battery focused on prefrontal
      functions. Significant correlations were found only between negative symptoms and
      measures of prevalent medial prefrontal functioning, i.e. decision making under
      ambiguity (Iowa gambling task) (r = -0.887; p = 0.018) and affective theory of
      mind (reading the mind in the eyes task) (r = -0.982; p = 0.017). This finding
      could preliminary support a "frontal lobe syndrome" hypothesis for negative
      symptoms of bvFTD patients, as proposed for negative symptoms of schizophrenia;
      the small sample size represents a limit and empirical findings need replication
      in larger samples of bvFTD patients.

PMID- 23532548
TI  - Nutraceuticals safety and efficacy in migraine without aura in a population of
      children affected by neurofibromatosis type I.
AB  - Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant
      disorders with a prevalence of one in 4,000 people worldwide, associated with
      many neurological comorbidities, such as headache. Despite the high prevalence of
      headache in this population, little data exist regarding the classification of
      headaches experienced by patients with NF1. Aim of this study is to verify the
      efficacy and safety of a nutraceutical complex containing Ginkgolide B/Coenzyme
      Q10/Riboflavin/Magnesium for prophylaxis in a sample of children affected by NF1
      presenting migraine without aura. Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium
      complex was orally administered twice a day for 6 months, to 18 school-aged
      patients with NF1 and presenting symptoms of migraine without aura (10 M, mean
      age 8.4 +/- 1.65). Each patient kept a journal to record: number, intensity
      (according VAS scale), duration of attacks and concomitant symptoms. In addition,
      the PedMIDAS scale was administered to assess migraine-related disability. To
      verify the efficacy of the association, we tested the starting frequency (T0) of
      headache after 6 months (T1) and then we calculated the migraine frequency delta
      percentage to express the decrease in monthly frequency. After treatment, a
      reduction was reported (p < 0.001) in all migraine outcomes (frequency, duration,
      intensity, and grade of disability). In conclusion, the present study should be
      considered as the first report on the efficacy and safety of nutraceutical
      complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for the
      prophylaxis of migraine in children affected by NF1. Our findings suggest that
      headache symptoms should be considered a therapeutic target independent of
      primary disorder.

PMID- 23532549
TI  - Altered intrinsic brain activity in patients with paroxysmal kinesigenic
      dyskinesia by PRRT2 mutation: altered brain activity by PRRT2 mutation.
AB  - The proline-rich transmembrane protein 2 (PRRT2) gene has been recently
      identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD), with
      an insertion mutation c.649_650insC (p.P217fsX7) reported as the most common
      mutation. However, the pathogenic mechanism of the mutation of PRRT2 remains
      largely unknown. Resting-state functional magnetic resonance imaging is a
      promising approach to assess cerebral function and reveals underlying functional
      changes. Resting-state functional magnetic resonance imaging was performed in 4
      Chinese PKD patients with p.P217fsX7 mutation, 6 Chinese PKD patients without the
      mutation, and 10 healthy control subjects. Voxel-based analysis was used to
      characterize alterations in the amplitude of low-frequency fluctuation (ALFF).
      When compared with the healthy control subjects, both groups of PKD patients
      showed alterations in spontaneous brain activities within cortical-basal ganglia
      circuitry. Besides, the group of patients with p.P217fsX7 mutation also exhibited
      increased ALFF in the right postcenral gyrus and right rolandic operculum area,
      while the alteration of ALFF in group of patients without the mutation
      additionally involved the middle orbitofrontal cortex. Direct comparative
      analysis between these two patient groups revealed significantly increased ALFF
      in the right postcentral gyrus in the group with p.P217fsX7 mutation. Increased
      spontaneous brain activity in the cortical-basal ganglia circuitry, especially in
      the motor preparation areas, is a common pathophysiology in PKD. Differences in
      the spatial patterns of increased ALFF between patients with and those without
      the mutation might reflect the distinct pathological mechanism resulting from
      PRRT2 mutation. 

PMID- 23532550
TI  - Theta burst stimulation improves visuo-spatial attention in a patient with
      traumatic brain injury.
AB  - Recent studies showed that non-invasive brain stimulation methods, such as
      repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of
      neglect in stroke patients. Here, we adopted this approach to improve visuo
      spatial deficit in a patient with traumatic brain injury (TBI) that showed
      important symptoms of visuo-spatial neglect. We found that continuous theta burst
      stimulation (cTBS) applied over the left posterior parietal cortex (PPC) induced
      a clinical improvement of cognitive disorder associated to a functional changes
      of fronto-parietal network as assessed by means of TMS and resting state fMRI. 

PMID- 23532551
TI  - Phylogeography of Human T-lymphotropic Virus Type 1 (HTLV-1) Lineages Endemic to
      Japan.
AB  - We conducted phylogenetic analyses and an estimation of coalescence times for
      East Asian strains of HTLV-1. Phylogenetic analyses showed that the following
      three lineages exist in Japan: "JPN", primarily comprising Japanese isolates;
      "EAS", comprising Japanese and two Chinese isolates, of which one originated from
      Chengdu and the other from Fujian; and "GLB1", comprising isolates from various
      locations worldwide, including a few Japanese isolates. It was estimated that the
      JPN and EAS lineages originated as independent lineages approximately 3,900 and
      6,000 years ago, respectively. Based on archaeological findings, the "Out of
      Sunda" hypothesis was recently proposed to clarify the source of the Jomon (early
      neolithic) cultures of Japan. According to this hypothesis, it is suggested that
      the arrival of neolithic people in Japan began approximately 10,000 years ago,
      with a second wave of immigrants arriving between 6,000 and 4,000 years ago,
      peaking at around 4,000 years ago. Estimated coalescence times of the EAS and JPN
      lineages place the origins of these lineages within this 6,000-4,000 year period,
      suggesting that HTLV-1 was introduced to Japan by neolithic immigrants, not Paleo
      Mongoloids. Moreover, our data suggest that the other minor lineage, GLB1, may
      have been introduced to Japan by Africans accompanying European traders several
      centuries ago, during or after "The Age of Discovery." Thus, the results of this
      study greatly increase our understanding of the origins and current distribution
      of HTLV-1 lineages in Japan and provide further insights into the ethno
      epidemiology of HTLV-1.

PMID- 23532552
TI  - Surgical approaches for cam femoroacetabular impingement: the use of
      multicriteria decision analysis.
AB  - BACKGROUND: Currently, three surgical approaches are available for the treatment
      of cam femoroacetabular impingement (FAI), namely surgical hip dislocation (SHD),
      hip arthroscopy (HA), and the miniopen anterior approach of the hip (MO).
      Although previous systematic reviews have compared these different approaches, an
      overall assessment of their performance is not available. QUESTIONS/PURPOSES: We
      therefore executed a multidimensional structured comparison considering the
      benefits, opportunities, costs, and risk (BOCR) of the different approaches using
      multicriteria decision analysis (MCDA). METHODS: A MCDA using analytic
      hierarchical process (AHP) was conducted to compare SHD, HA, and MO in terms of
      BOCR on the basis of available evidence, institutional experience, costs, and our
      understanding of pathophysiology of FAI. A preclinical decision-making model was
      created for cam FAI to establish the surgical approach that better accomplishes
      our objectives regarding the surgical treatment. A total score of an
      alternative's utility and sensitivity analysis was established using commercially
      available AHP software. RESULTS: The AHP model based on BOCR showed that MO is
      the best surgical approach for cam FAI (normalized score: 0.38) followed by HA
      (normalized score: 0.36) and SHD (normalized score: 0.25). The sensitivity
      analysis showed that HA would turn into the best alternative if the variable
      risks account for more than 61.8% of the priority during decision-making. In any
      other decision-making scenario, MO remains as the best alternative. CONCLUSIONS:
      Using a recognized method for decision-making, this study provides supportive
      data for the use of MO approach as our preferred surgical approach for cam FAI.
      The latter is predominantly derived from the lower cost of this approach. Our
      data may be considered a proxy performance measurement for surgical approaches in
      cam FAI.

PMID- 23532553
TI  - Association of body mass index with major cardiovascular events and with
      mortality after percutaneous coronary intervention.
AB  - BACKGROUND: Conflicting data exist regarding the relation between body mass index
      (BMI) and cardiovascular events and mortality after percutaneous coronary
      intervention. METHODS AND RESULTS: We performed pooled analyses to evaluate the
      association between BMI (weight in kilograms divided by the square of the height
      in meters) and the risks of major cardiovascular events (defined as death from
      cardiovascular causes, nonfatal myocardial infarction, stent thrombosis, or
      stroke) and death among 23 181 patients from 11 prospective percutaneous coronary
      intervention studies. Overall, mean (+/-SD) BMI was 24.9+/-3.0. During follow-up
      (median, 2.1 years), 2381 patients had a major cardiovascular event, and 1004
      patients died. After adjusting covariates, there was an inverse relationship
      between BMI and adverse outcomes. With a BMI of 22.5 to 24.9 as the reference
      category, the risk of major cardiovascular events was elevated among patients
      with a lower BMI (by a factor of 1.52 for a BMI <18.5; 1.05 for a BMI of 18.5
      19.9; 1.03 for a BMI of 20.0-22.4); by contrast, the risk declined among patients
      with a higher BMI (by a factor of 0.97 for a BMI of 25.0-27.4; 0.97 for a BMI of
      27.5-29.9; and 0.78 for a BMI of >=30.0). In general, the hazard ratios for
      deaths were similar. CONCLUSIONS: Among patients undergoing percutaneous coronary
      intervention, a low BMI was associated with increased risks of major
      cardiovascular events and death. However, there were no excess risks of these
      events associated with a high BMI.

PMID- 23532554
TI  - Hemorrhagic and ischemic outcomes after bivalirudin versus unfractionated heparin
      during carotid artery stenting: a propensity score analysis from the NCDR.
AB  - BACKGROUND: The direct thrombin inhibitor, bivalirudin, is associated with
      similar efficacy and superior safety in patients undergoing percutaneous coronary
      intervention. However, the role of direct thrombin inhibitors in carotid artery
      stenting is not well defined. The objective of this study was to compare the
      safety and effectiveness of bivalirudin and unfractionated heparin (UFH) for
      carotid artery stenting. We hypothesized that bivalirudin would be associated
      with less in-hospital postprocedure bleeding than UFH but similar rates of in
      hospital and 30-day ischemic outcomes. METHODS AND RESULTS: We compared the
      incidence of in-hospital hemorrhagic and in-hospital/30-day ischemic outcomes
      among patients in the CARE Registry who underwent carotid artery stenting between
      May 2005 and March 2012 using bivalirudin or UFH. Propensity score matching was
      used to obtain a balanced cohort of 3555 patients in each treatment group.
      Patients treated with bivalirudin had a significantly lower incidence of bleeding
      or hematoma requiring red blood cell transfusions (0.9% versus 1.5%; odds ratio,
      0.57 [0.36-0.89]; P=0.01) when compared with UFH-treated patients. The incidence
      of in-hospital and 30-day ischemic outcomes, including death, myocardial
      infarction, stroke, transient ischemic attack, and the composite outcome,
      death/myocardial infarction/stroke, did not differ significantly between groups.
      CONCLUSIONS: Bivalirudin was associated with lower rates of hemorrhagic outcomes
      compared with UFH during the index hospitalization for carotid artery stenting.
      In-hospital and 30-day ischemic events were similar between the 2 groups.
      Randomized comparisons of these agents are needed to confirm these findings.

PMID- 23532555
TI  - Pill burden in hypertensive patients treated with single-pill combination therapy
      -an observational study.
AB  - INTRODUCTION: Hypertension is a condition which in many cases is treated with
      more than one drug. Additionally, patients with hypertension often suffer from
      other concomitant diseases, such as diabetes mellitus or dyslipidemia, which adds
      to the number of pills that patients need to take (pill burden). The aim of this
      study was to investigate the impact of this pill burden on patients with
      hypertension in clinical practice in Germany. METHODS: This prospective, open
      label, observational study enrolled adult patients for whom their physician
      considered treatment with a single-pill combination of amlodipine, valsartan, and
      hydrochlorothiazide as indicated. At the start of the observation period,
      physicians and patients filled in a respective questionnaire. RESULTS: The
      questionnaires of 7,101 patients and 905 physicians were analyzed. The survey
      among the patients showed that the majority of patients felt burdened by the high
      number of pills to be taken. This was also seen as a potential reason for
      medication errors. Approximately half of the patients would be willing to make an
      out-of-pocket payment for reducing the number of pills to half. The results of
      the physician questionnaire indicate that the physicians were well aware of the
      set of problems that is generally associated with the high pill burden and that
      there is a clear willingness to use combination products in order to reduce the
      pill burden. CONCLUSION: A high number of pills is considered a burden by the
      patients. This burden increases with the number of pills taken per day.

PMID- 23532556
TI  - Do angiotensin receptor blockers protect against Alzheimer's disease?
AB  - Because growing evidence suggests that angiotensin II receptor blockers (ARBs)
      effectively inhibit oxidative stress, amyloid beta protein (Abeta) metabolism,
      and tau phosphorylation in animal brains, ARBs are considered to be a potential
      candidate for the treatment of Alzheimer's disease (AD). Consistent with such
      basic studies, two recent observational studies and a small prospective,
      randomized, open-label trial have shown the effectiveness of ARBs in preventing
      AD and/or slowing its progression. Nonetheless, large clinical trials have not
      shown their effectiveness, but their results are debatable because of short
      follow-up durations and heterogeneity of the cognition assessments used in the
      studies. Because a recent analysis of the Honolulu-Asia Aging study showed that
      abnormalities of the serum Abeta level begin approximately 15 years before the
      diagnosis of AD, long-term clinical trials assessing dementia as a primary
      endpoint with sensitive measurements of cognition and brain imaging techniques
      will clarify the effectiveness of ARBs in AD treatment.

PMID- 23532557
TI  - Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer.
AB  - The taxane derivative cabazitaxel (Jevtana((r))) is approved in the USA and the
      EU for use in combination with prednisone for the treatment of patients with
      hormone-refractory metastatic prostate cancer previously treated with a docetaxel
      containing regimen. In the pivotal TROPIC trial, overall survival was
      significantly prolonged with cabazitaxel plus prednisone versus mitoxantrone plus
      prednisone in patients with metastatic castration-resistant prostate cancer who
      had progressed during or after docetaxel therapy. In addition, progression-free
      survival, the times to tumour progression and prostate specific antigen (PSA)
      progression, and tumour and PSA response rates were improved with cabazitaxel
      plus prednisone. Intravenous cabazitaxel had an acceptable tolerability profile,
      with haematological adverse events occurring most commonly, and diarrhoea being
      the most common nonhaematological adverse event.

PMID- 23532558
TI  - Progressive neurolymphomatosis with cutaneous disease: response in a patient with
      mycosis fungoides.
AB  - Peripheral neurolymphomatosis is a rare manifestation of advanced
      lymphoproliferative disorders. It is often associated with B cell lymphomas and
      rarely with cutaneous T cell lymphomas, such as mycosis fungoides and Sezary
      syndrome. In this case report, we present a 78-year-old male with a long-standing
      history of mycosis fungoides. The patient initially presented with chronic
      peripheral neuropathy in an ulnar nerve distribution. After an unsuccessful ulnar
      nerve transposition, the ulnar nerve was re-explored and a mass consistent with
      diffuse lymphomatous infiltration was diagnosed. Magnetic resonance (MR) imaging
      of the left brachial plexus and later of the sacral plexus demonstrated diffuse
      thickening and peripheral nodularity in keeping with neurolymphomatosis. The
      patient's clinical course rapidly deteriorated thereafter and the patient
      succumbed to his disease. Although uncommon, neurolymphomatosis may be considered
      in patients with chronic peripheral neuropathy and an underlying history of a
      lymphoproliferative disorder. US and MR may serve as helpful non-invasive
      adjuncts in making the diagnosis and identifying sites for biopsy.

PMID- 23532559
TI  - Calcific discitis in an adult patient with intravertebral migration and
      spontaneous remission.
AB  - Symptomatic disc calcifications have been reported, especially in the pediatric
      population, and remain of unknown etiology. Such a condition has been very rarely
      reported in adults. The aim of this paper is to present a case report of calcific
      discitis in an adult patient with intravertebral migration and spontaneous
      calcification resorption. The clinical presentation was that of back pain with an
      abrupt onset, not related to trauma or to physical activity. No fever or
      neurological deficits were present. Blood count, erythrocyte sedimentation rate,
      routine urine, and urine culture were negative. The pain regressed in 20 days
      with analgesic therapy. Findings of thoracic calcific discitis are illustrated
      with X-rays, CT, MRI, and bone scintigraphy. 

PMID- 23532560
TI  - Accuracy analysis in MRI-guided robotic prostate biopsy.
AB  - PURPOSE: To assess retrospectively the clinical accuracy of an magnetic resonance
      imaging-guided robotic prostate biopsy system that has been used in the US
      National Cancer Institute for over 6 years. METHODS: Series of 2D transverse
      volumetric MR image slices of the prostate both pre (high-resolution T2-weighted)
      and post (low-resolution)- needle insertions were used to evaluate biopsy
      accuracy. A three-stage registration algorithm consisting of an initial two-step
      rigid registration followed by a B-spline deformable alignment was developed to
      capture prostate motion during biopsy. The target displacement (distance between
      planned and actual biopsy target), needle placement error (distance from planned
      biopsy target to needle trajectory), and biopsy error (distance from actual
      biopsy target to needle trajectory) were calculated as accuracy assessment.
      RESULTS: A total of 90 biopsies from 24 patients were studied. The registrations
      were validated by checking prostate contour alignment using image overlay, and
      the results were accurate to within 2 mm. The mean target displacement, needle
      placement error, and clinical biopsy error were 5.2, 2.5, and 4.3 mm,
      respectively. CONCLUSION: The biopsy error reported suggests that quantitative
      imaging techniques for prostate registration and motion compensation may improve
      prostate biopsy targeting accuracy.

PMID- 23532561
TI  - Nutrient-based dietary patterns of head and neck squamous cell cancer: a factor
      analysis in Uruguay.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      nutrient-based dietary patterns and squamous cell cancers of the head and neck.
      METHODS: We used a case-control study which included 548 cases and 548 controls.
      From these participants, we derived 23 nutrients and they were then submitted to
      a factorability analysis in order to conduct a principal component factor
      analysis. RESULTS: We were able to identify four nutrient-derived patterns. The
      first pattern (meat-based pattern) was positively associated with squamous cell
      cancer of the head and neck (OR 2.85, 95 % CI 1.81-4.15), whereas the third
      pattern (fruit-based) was strongly protective (OR 0.43, 95 % CI 0.27-0.63). The
      other nutrient patterns were also significantly associated with head and neck
      squamous cell carcinoma with minor ORs. CONCLUSION: Both patterns suggest that
      red meat and fruits are major factors in the etiology of head and neck squamous
      cell cancer, replicating previous studies in the field.

PMID- 23532562
TI  - Estrogen deficiency inhibits the odonto/osteogenic differentiation of dental pulp
      stem cells via activation of the NF-kappaB pathway.
AB  - Various factors can affect the functions of dental pulp stem cells (DPSCs).
      However, little knowledge is available about the effects of estrogen deficiency
      on the differentiation of DPSCs. In this study, an estrogen-deficient rat model
      was constructed and multi-colony-derived DPSCs were obtained from the incisors of
      ovariectomized (OVX) or sham-operated rats. Odonto/osteogenic differentiation and
      the possible involvement of the nuclear factor kappa B (NF-kappaB) pathway in the
      OVX-DPSCs/Sham-DPSCs of these rats were then investigated. OVX-DPSCs presented
      decreased odonto/osteogenic capacity and an activated NF-kappaB pathway, as
      compared with Sham-DPSCs. When the cellular NF-kappaB pathway was specifically
      inhibited by BMS345541, the odonto/osteogenic potential in OVX-DPSCs was
      significantly upregulated. Thus, estrogen deficiency down-regulated the
      odonto/osteogenic differentiation of DPSCs by activating NF-kappaB signaling and
      inhibition of the NF-kappaB pathway effectively rescued the decreased
      differentiation potential of DPSCs.

PMID- 23532563
TI  - Social stress models in depression research: what do they tell us?
AB  - Interest has recently surged in the use of social stress models, especially
      social defeat. Such interest lies both in the recognition that stressors of
      social origin play a major role in human psychopathologies and in the
      acknowledgement that natural and hence ethologically-based stress models have
      important translational value. The use of the most recent technology has allowed
      the recognition of the mechanisms through which social defeat might have enduring
      psychoneuroendocrine effects, especially social avoidance and anhedonia, two
      behaviours relevant to human depression. In view of the sensitivity of these
      behavioural outcomes to repeated antidepressant treatments, the social defeat
      model has been proposed as a possible animal model of depression. The present
      survey is aimed at examining the limits of such an interpretation and focuses on
      methodological aspects and on the relevance of social defeat to the study of
      anxiety-related pathologies. 

PMID- 23532564
TI  - Prospective clinical trial of diagnostic peritoneal lavage to detect positive
      peritoneal cytology in patients with gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Positive peritoneal cytology equates M1 disease in
      patients with gastric cancer. Diagnostic peritoneal lavage (DPL) is a proven test
      to detect occult visceral injury in trauma patients. The objective of this study
      is to determine whether DPL can be used to assess peritoneal cytology in patients
      with gastric cancer. METHODS: Patients with gastric adenocarcinoma were
      prospectively enrolled to undergo DPL prior to diagnostic laparoscopy (DL).
      Saline was instilled through a percutaneous catheter and fluid was collected for
      cytology (DPL-cyt). Washings obtained during DL were used as controls (DL-cyt).
      RESULTS: DPL was successful in 22/27 patients (81.5%). Among the 22 successful
      DPLs, 12 had positive cytology (54.5%). Positive DPL-cyt specimens matched DL-cyt
      specimens in 12/12 cases (specificity = 100%). One of 10 cases with negative DPL
      cyt was positive on the final DL-cyt (sensitivity = 92%). There were six patients
      with negative DPL-cyt who had visible M1 disease diagnosed with DL (DPL
      evaluation of M1 disease, sensitivity 54.5%, specificity = 100%). CONCLUSIONS:
      DPL is a safe method of detecting positive cytology in patients with gastric
      cancer, however gross M1 disease may be missed without visual inspection. The
      specific role of DPL in the staging workup of patients with gastric cancer
      remains to be determined.

PMID- 23532566
TI  - Yeast-incorporated gallium attenuates glucocorticoid-induced bone loss in rats by
      inhibition of bone resorption.
AB  - Glucocorticoids (GC) are potent anti-inflammatory agents and widely used for the
      treatment of many immune-mediated and inflammatory diseases, whereas GC-induced
      osteoporosis (GIOP) is the most common cause of secondary osteoporosis and
      significantly increases the patients' morbidity and mortality. GIOP is
      characterized as diminished osteogenesis and accelerated bone resorption. Yeast
      incorporated gallium (YG) as an organic compound not only reduces elements
      associated toxicity, but also maintains its therapeutic effect on improving bone
      loss or promoting fracture healing in ovariectomized female rats. The aim of this
      study was to examine whether YG could prevent GC-induced bone loss. Five-month
      old male Sprague-Dawley rats were randomly divided into three groups (n = 6): two
      groups were administered dexamethasone (0.1 mg/kg/day) or vehicle (PBS)
      subcutaneously for 5 weeks; one other group was received dexamethasone
      subcutaneously and YG (120 MUg/kg/day) orally. Trabecular bone microarchitectural
      parameters, bone mineral density (BMD), bone strength, body weight, and serum
      biochemical markers of bone resorption and formation were examined. Compared to
      the GC alone group, treatment with YG not only prevented microarchitectural
      deterioration of trabecular bone volume relative to tissue volume, trabecular
      number, and trabecular separation, but also significantly improved BMD,
      mechanical strength, and body weight in GC-treated rats. Moreover, YG decreased
      tartrate-resistant acid phosphatase 5b level but failed to change alkaline
      phosphatase level in GC-treated rats. This is the first study to show that YG
      prominently attenuates bone loss and microarchitectural deterioration and
      inhibits the increased bone resorption in GIOP. It implies that YG might be an
      alternative therapy for prevention of GC-induced bone loss in humans.

PMID- 23532565
TI  - Examining the associations between overeating, disinhibition, and hunger in a
      nonclinical sample of college women.
AB  - BACKGROUND: Binge eating (BE) has long been identified as a correlate of
      overweight and obesity. However, less empirical attention has been given to
      overeating with and without loss of control (LOC) in nonclinical samples.
      PURPOSE: The goal of the present study was to examine the association of (1)
      established correlates of BE, namely, weight and shape concerns, dietary
      restraint, and negative affect, and (2) three additional correlates,
      disinhibition, hunger, and interoceptive awareness (IA), to overeating in a
      nonclinical sample of college women. METHOD: Female students (n = 1,447) aged 18
      to 21 years recruited from colleges in three Canadian metropolitan areas
      completed self-report questionnaires in class to assess sociodemographic and
      anthropomorphic characteristics, overeating, LOC, dietary restraint, negative
      affect, weight and shape concerns, IA, disinhibition, and hunger. RESULTS: The
      established correlates of BE were significant correlates of all types of
      overeating and explained 33 % of the variance. Disinhibition was the most
      strongly associated correlate of overeating. CONCLUSIONS: Findings suggest that
      established correlates of BE are associated with other types of overeating such
      as objective overeating (OOE), as are disinhibition and hunger.

PMID- 23532567
TI  - Incidence, risk factors, and outcome of postoperative pneumonia after
      microsurgical clipping of ruptured intracranial aneurysms.
AB  - BACKGROUND: Occurrence of pneumonia challenges the medical management of patients
      who have undergone surgery for aneurysmal subarachnoid hemorrhage, and is
      associated with significant mortality and morbidity. There are very few studies
      evaluating the incidence and outcome of postoperative pneumonia in patients
      undergoing microsurgical clipping of ruptured intracranial aneurysms. The aim of
      this study was to determine the incidence, risk factors, and outcome of
      postoperative pneumonia in patients undergoing surgery for ruptured intracranial
      aneurysms. METHODS: All patients operated for intracranial aneurysms, over a
      period of 9 months, were included prospectively. They were studied for risk
      factors predisposing them to pneumonia and their outcomes were noted at
      discharge. Patients with predisposing chronic lung disease, preexisting
      pneumonia, and chronic smoking habits were excluded. RESULTS: ONE HUNDRED AND
      THREE PATIENTS [MEAN AGE: 46.01 years; M:F - 58:45] underwent microsurgical
      clipping of aneurysm during the study period. Of these, 28 patients (27.2%)
      developed postoperative pneumonia. The variables associated with postoperative
      pneumonia were: [Preoperative] age >50 years, Glasgow Coma Scale (GCS) at
      presentation <15 and Hunt and Hess grade before surgery >2; [postoperative]
      duration of surgery >3 hours, GCS <15 after complete reversal from anesthesia,
      duration of intubation in the postoperative period >48 hours, tracheostomy,
      postoperative ventilation, intensive care unit (ICU) stay >5 days. Predictive
      factors for postoperative pneumonia by multivariate analysis were: Postoperative
      endotracheal intubation >48 hours, tracheostomy and ICU stay >5 days.
      CONCLUSIONS: There is a high incidence of postoperative pneumonia and mortality
      associated with pneumonia (27.2% and 9.7%, respectively in our study) in patients
      of ruptured intracranial aneurysms undergoing microsurgical clipping at our
      center, with Acinetobacter species being the predominant causative organism.

PMID- 23532568
TI  - Association between use of air-conditioning or fan and survival of elderly
      febrile patients: a prospective study.
AB  - Elderly individuals are more susceptible to excess summer heat. We sought to
      examine whether the use of cooling systems (air-conditioning or fan) affected the
      clinical outcomes of elderly febrile patients. We prospectively followed elderly
      (>= 75 years old) febrile patients requesting the medical services of the SOS
      Doctors (a network of physicians performing house-call visits) from July 10 to
      August 20, 2011. Patients who used cooling systems ("users") were compared with
      those who did not ("non-users") regarding mortality, clinical outcome of primary
      illness (improvement or deterioration), and emergency hospitalization.
      Prospectively collected data were available for 339 individual elderly febrile
      patients. "Users" had lower mortality (10 % vs. 19 %, p < 0.05) than "non-users";
      no difference was noted on clinical improvement (85 % vs. 76 %, p = 0.11) and
      emergency hospitalization rates (21 % vs. 30 %, p = 0.16). No difference was
      noted between users of air-conditioning and fan regarding mortality or clinical
      improvement, but fan use was associated with more hospitalizations (37 % vs. 19
      %, p < 0.05). On multivariate analysis (assessing daily ambient temperature, use
      of cooling systems, patient age, and living conditions), the sole variable
      significantly associated with mortality was the non-use of cooling systems [odds
      ratio (OR): 2.18, 95 % confidence interval (CI): 1.06-4.50]. The use of air
      conditioning or fan during hot summer periods appeared to be beneficial for
      elderly febrile patients living in a large city. Large prospective studies are
      warranted in order to provide further insight into potential individual and
      public health initiatives aiming to alleviate the impact of excess summer heat on
      the health of elderly patients.

PMID- 23532570
TI  - Asthma self-management: a study in an emergency room of a chest hospital in
      delhi, India.
AB  - OBJECTIVES: Poorly controlled asthma imposes a considerable burden and is a
      serious public health problem in the developing world. A key challenge for
      healthcare professionals is to help patients to engage in self-management
      behaviours with optimal adherence to appropriate treatment. The aim of the
      present study was to investigate the pattern of self-management in asthmatic
      patients enrolled as out-patients in a tertiary care referral public chest
      hospital, in Delhi, India. METHODS: The study population was adult asthma
      patients (n=200) visiting the emergency room (December 2008-December 2009) of a
      chest hospital for asthma exacerbation. The data was collected through a
      questionnaire regarding the self-management of asthma. RESULTS: Enrolled patients
      (64.0% female) were registered as asthma out-patients in the study hospital for a
      mean of 5.4+/-4.4 years. Patients visiting the emergency room (ER) and having an
      unscheduled visit to doctor at least twice in the previous 12 months were 86.5%
      and 91.0%. Patients were classified according to the disease severity as having
      intermittent (17.0%) or persistent (83.0%) asthma. Not all patients had metered
      dose inhalers at home. Only 2.0% of patients were prescribed peak flow meters and
      were keeping a diary of their readings. With one exception, patients did not have
      written action plans for treatment provided by doctor or health facility. No
      statistical difference was found in the pattern of self-management of patients
      having persistent or intermittent asthma. CONCLUSIONS: Findings revealed poor
      self-management of asthma and poor communication from doctors regarding self
      management to the patients. Suitable actions and interventions are needed by
      health professionals to implement patient self-management asthma programme for
      optimum asthma control.

PMID- 23532569
TI  - Assessment of the efficacy of polyclonal intravenous immunoglobulin G (IVIG)
      against the infectivity of clinical isolates of methicillin-resistant
      Staphylococcus aureus (MRSA) in vitro and in vivo.
AB  - The response to treatment of severe methicillin-resistant Staphylococcus aureus
      (MRSA) infections with the traditional antibiotics is sometimes unsatisfactory
      and multiple antibiotic resistance is common. Adjuvant therapy such as
      intravenous immunoglobulin G (IVIG) could possibly be helpful in the treatment of
      such infections. The effect of IVIG on the capacity of human neutrophils to
      phagocytose and kill MRSA was investigated in vitro using the MTT assay and
      measuring the production of reactive oxygen species (ROS) and nitric oxide (NO).
      The efficiency of IVIG in neutralizing alpha-hemolysin and coagulase of MRSA was
      also assessed. The capability of IVIG in the treatment and prevention of MRSA
      infections was also evaluated in a murine peritonitis model. IVIG significantly
      enhanced (p < 0.01) the killing of MRSA by neutrophils at all concentrations
      tested (0.1-5 mg/ml) by 30-80 % of control values. It significantly (p < 0.01)
      increased the level of NO production in a dose-dependent manner, giving up to 60
      MUM at 5 mg/ml. The ROS level significantly increased (p < 0.01) in the presence
      of IVIG. In addition, IVIG significantly reduced the hemolytic activity of MRSA
      10-fold and its coagulation capabilities by 50 %. When tested in vivo, groups
      receiving IVIG via tail vein infusion showed no significant improvement in their
      survival. Only when delivered to the same site of infection did IVIG show an
      improvement in the survival of mice (n = 80). These results could pave the way
      for a better understanding of the mechanism of action of IVIG and suggest its
      clinical potential as an adjuvant preventive and therapeutic agent against life
      threatening infections caused by MRSA and other bacteria.

PMID- 23532571
TI  - [Combination of two depot antipsychotic drugs].

PMID- 23532572
TI  - [Vestibular migraine: diagnostic criteria: consensus document of the Barany
      Society and the International Headache Society].

PMID- 23532573
TI  - Urokinase plasminogen activator receptor: a functional integrator of
      extracellular proteolysis, cell adhesion, and signal transduction.
AB  - The urokinase plasminogen activator receptor (uPAR) is a cell surface receptor
      involved in a multitude of physiologic and pathologic processes. uPAR regulates
      simultaneously a branch of the plasminogen activator system and modulates cell
      adhesion and intracellular signaling by interacting with extracellular matrix
      components and signaling receptors. The multiple uPAR functions are deeply
      interconnected, and their integration determines the effects that uPAR expression
      triggers in different contexts. The proteolytic function of uPAR affects both the
      signaling and the adhesive functions of the receptor, whereas these latter two
      are closely interconnected. This review focuses on the molecular mechanisms that
      connect and mutually regulate the different uPAR functions.

PMID- 23532574
TI  - The apparent uPA/PAI-1 paradox in cancer: more than meets the eye.
AB  - The expression of several components of the plasminogen-plasmin (P-P) system in
      tumor tissues has been shown to have prognostic significance in many human
      cancers, including those of the breast, prostate, lung, brain, ovary, stomach,
      colon, rectum, oral cavity, kidney, and bone. Mechanisms of action of the
      individual components have been extensively studied in tumor cells in vitro and
      in animal models. By interrupting various putative pathways involved in tumor
      progression in several experimental tumor models in animals, varying degrees of
      tumor control have been achieved. However, these efforts have thus far not been
      able to exert any impact in oncologic clinical practice. A possible explanation
      is our incomplete understanding of the complex involvement of the P-P system and
      its interactions with other tumorigenic factors. In this article, the role of
      various members of the P-P system in cancer is reviewed. Proteolysis via the
      urokinase-type plasminogen activator-plasminogen activation pathway tends to
      enhance tumor growth and invasion, and its natural inhibitor plasminogen
      activator inhibitor type 1 may also enhance tumor growth through the inhibition
      of apoptosis, enhancing cell proliferation and the promotion of angiogenesis.
      Meaningful drug designs for therapeutic intervention require a thorough
      understanding of the role of all of the components involved in this complex
      mechanism of tumor progression.

PMID- 23532576
TI  - Gastrointestinal adverse effects of short-term aspirin use: a meta-analysis of
      published randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVES: Aspirin is widely used for short-term treatment of
      pain, fever or colds, but there are only limited data regarding the safety of
      this use. To summarize the available data on this topic, we conducted a meta
      analysis of the published clinical trial literature regarding the
      gastrointestinal adverse effects of short-term use of aspirin in comparison with
      placebo and other medications commonly used for the same purpose. DATA SOURCES
      AND METHODS: An extensive literature search identified 119,310 articles regarding
      possible adverse effects of aspirin, among which 23,131 appeared to possibly
      include relevant data. An automated text-mining procedure was used to score the
      references for potential relevance for the meta-analysis. The 3,983 highest
      scoring articles were reviewed individually to identify those with data that
      could be included in this analysis. Ultimately, 78 relevant articles were
      identified that contained gastrointestinal adverse event data from clinical
      trials of aspirin versus placebo or an active comparator. Odds ratios (ORs)
      computed using a Mantel-Haenszel estimator were used to summarize the comparative
      effects on dyspepsia, nausea/vomiting, and abdominal pain, considered separately
      and also aggregated as 'minor gastrointestinal events'. Gastrointestinal bleeds,
      ulcers, and perforations were also investigated. RESULTS: Data were obtained
      regarding 19,829 subjects (34 % treated with aspirin, 17 % placebo, and 49 % an
      active comparator). About half of the aspirin subjects took a single dose.
      Aspirin was associated with a higher risk of minor gastrointestinal events than
      placebo or active comparators: the summary ORs were 1.46 (95 % confidence
      interval [CI] 1.15-1.86) and 1.81 (95 % CI 1.61-2.04), respectively. Ulcers,
      perforation, and serious bleeding were not seen after use of aspirin or any of
      the other interventions. CONCLUSIONS: During short-term use, aspirin is
      associated with a higher frequency of gastrointestinal complaints than other
      medications commonly used for treatment of pain, colds, and fever. Serious
      adverse events were not observed with aspirin or any of the comparators.

PMID- 23532577
TI  - Solvent-dispersed benzothiadiazole-tetrathiafulvalene single-crystal nanowires
      and their application in field-effect transistors.
AB  - A new organic semiconductor (BT-TTF) based on molecular moieties of
      benzothiadiazole and tetrathiafulvalene was designed and synthesized, and its
      structure, molecular packing and charge-transporting properties were determined.
      Thermal properties, electrochemical behaviors, and optical absorption of this
      molecule were studied by using differential scanning calorimetry/thermal
      gravimetric analysis, cyclic voltammetry, and ultraviolet-visible spectroscopy,
      respectively. Its bulk and nanowire single crystals were prepared and
      characterized by X-ray crystallography, scanning electron microscopy,
      transmission electron microscopy, and field-effect transistors. It is found that
      short intermolecular S...S (3.41 A), S...C (3.49 A), and S...N (3.05 A) contacts
      define the solid-state structure of BT-TTF single crystals which pi-stack along
      the [100] with interplanar distances of 3.49 A. Solvent-cast single-crystal
      nanowire transistors showed mobilities as large as 0.36 cm2/(V s) with current
      on/off ratios of 1*10(6). This study further illustrates the impact of molecular
      design and a demonstration of high-performance single-crystal nanowire
      transistors from the resulting semiconductor.

PMID- 23532575
TI  - Plasminogen receptors: the first quarter century.
AB  - The interaction of plasminogen with cell surfaces results in promotion of plasmin
      formation and retention on the cell surface. This results in arming cell surfaces
      with the broad-spectrum proteolytic activity of plasmin. Over the past quarter
      century, key functional consequences of the association of plasmin with the cell
      surface have been elucidated. Physiologic and pathophysiologic processes with
      plasmin-dependent cell migration as a central feature include inflammation, wound
      healing, oncogenesis, metastasis, myogenesis, and muscle regeneration. Cell
      surface plasmin also participates in neurite outgrowth and prohormone processing.
      Furthermore, plasmin-induced cell signaling also affects the functions of
      inflammatory cells, via production of cytokines, reactive oxygen species, and
      other mediators. Finally, plasminogen receptors regulate fibrinolysis. In this
      review, we highlight emerging data that shed light on longstanding controversies
      and raise new issues in the field. We focus on (1) the impact of the recent X-ray
      crystal structures of plasminogen and the development of antibodies that
      recognize cell-induced conformational changes in plasminogen on our understanding
      of the interaction of plasminogen with cells; (2) the relationship between
      apoptosis and plasminogen binding to cells; (3) the current status of our
      understanding of the molecular identity of plasminogen receptors and the
      discovery of a structurally unique novel plasminogen receptor, Plg-RKT; (4) the
      determinants of the interplay between distinct plasminogen receptors and cellular
      functions; and (5) new insights into the role of colocalization of plasminogen
      and plasminogen activator receptors on the cell surface.

PMID- 23532578
TI  - Implicit and explicit learning in individuals with agrammatic aphasia.
AB  - Implicit learning is a process of acquiring knowledge that occurs without
      conscious awareness of learning, whereas explicit learning involves the use of
      overt strategies. To date, research related to implicit learning following stroke
      has been largely restricted to the motor domain and has rarely addressed
      implications for language. The present study investigated implicit and explicit
      learning of an auditory word sequence in 10 individuals with stroke-induced
      agrammatic aphasia and 18 healthy age-matched participants using an adaptation of
      the Serial Reaction Time task. Individuals with aphasia showed significant
      learning under implicit, but not explicit, conditions, whereas age-matched
      participants learned under both conditions. These results suggest significant
      implicit learning ability in agrammatic aphasia. Furthermore, results of an
      auditory sentence span task indicated working memory deficits in individuals with
      agrammatic aphasia, which are discussed in relation to explicit and implicit
      learning processes. 

PMID- 23532579
TI  - A ciliated foregut cyst in a gallbladder: the smallest recorded.
AB  - Ciliated foregut cysts (CFCs) are rare masses that develop from the tissues which
      remain from embryological foregut development. In the literature, about a hundred
      cases have been described in various organs so far. Although rare, there is a
      risk of development of squamous cell carcinoma from these cysts that typically
      bear benign features. Prognosis following the development of carcinoma is poor. A
      female case presented with upper quadrant pain and was sent to radiology for US
      examination of the abdomen. In 2010, a cyst which was about 5 mm in size was
      detected on the wall of the gall bladder. In subsequent US, the lesion reached 7
      mm in diameter and a shape protruding to the lumen was included in the findings;
      therefore, it was decided to operate. The mass was diagnosed as a CFC of the
      gallbladder. We determined that the lesion had the smallest dimension noted in
      the literature. Congenital gallbladder cysts are detected rather rarely. The US
      characteristics are enough to make a definitive diagnosis, and the other imaging
      methods therefore remain unnecessary. Treatment using a laparoscopic surgical
      method is the first preference.

PMID- 23532580
TI  - Optical properties of root canal irrigants in the 300-3,000-nm wavelength region.
AB  - In root canal therapy, irrigating solutions are essential to assist in
      debridement and disinfection. Their spread and action is often restricted by
      canal anatomy, requiring some form of activation. Lasers have been shown to be
      promising tools for this purpose (laser-activated irrigation (LAI)). For LAI to
      be effective, high absorption of radiation in the irrigant is essential. Although
      the absorption spectrum of water is well established, little is known about the
      optical properties of other irrigating solutions. Therefore, root canal irrigants
      (sodium hypochlorite (NaOCl), citric acid (CA), chlorhexidine (CHX),
      ethylenediaminetetraacetate (EDTA), water) were subjected to UV/Vis
      spectrophotometry in the 300-3,000-nm region using synthetic quartz cells with an
      optical path length of 1 mm. Transmission data were used to plot the transmission
      spectrum and calculate the absorption coefficient (alpha) of each irrigant. The
      transmission spectra of the tested solutions proved to follow the spectrum of
      pure water to a large extent. All tested solutions displayed absorption peaks
      around 1,450 nm (alpha ~ 14 cm(-1)), 1,950 nm (alpha > 30 cm(-1)), and above
      2,500 nm (alpha > 30 cm(-1)). NaOCl showed higher absorption than water in the UV
      region. Slightly higher absorption than water was noted for CHX (Corsodyl) around
      513 nm and for CA between 1,600 and 1,800 nm and around 2,200 nm. The absorption
      in all tested solutions for wavelengths greater than 2,500 nm is very high,
      meaning a great potential for laser-activated irrigation. Other wavelengths
      eligible for LAI are located around 1,450 and 2,000 nm but require further
      investigation.

PMID- 23532581
TI  - Rho-kinase inhibitor Y-27632 attenuates arsenic trioxide toxicity in H9c2
      cardiomyoblastoma cells.
AB  - The purpose of this study is to examine the molecular mechanism underlying the
      toxicity of arsenic trioxide (ATO) in cardiac cells. H9c2 rat cardiomyoblastoma
      cells undergo apoptosis during exposure to the concentrations of ATO > 10 MUM for
      24 h. The process is accompanied by the activation of caspases and is suppressed
      by the pan-caspase inhibitor z-VAD. Since ATO-induced H9c2 cell death is
      suppressed by Rho-kinase (ROCK) inhibitor Y-27632, but not by any antioxidants
      tested, apoptosis by ATO seems to be initiated through a ROCK-dependent and
      reactive oxygen species-independent mechanism. During the execution of apoptosis
      by ATO, the induction of autophagy is also observed. Importantly, autophagy is
      accelerated in cells treated with ATO plus Y-27632, although Y-27632 alone does
      not induce autophagy. The cytoprotective effect of Y-27632 against ATO toxicity
      is abrogated by the co-administration of an autophagy inhibitor, 3-methyladenine,
      suggesting that autophagy contributes to the cytoprotection by Y-27632. Taken
      together, the data indicate that the activation of ROCK is required for apoptotic
      H9c2 cardiomyoblastoma cell death by ATO, and that the ROCK inhibition not only
      inhibits caspase-dependent apoptotic machinery, but also causes a rise in the
      cytoprotective autophagy processes during ATO exposure.

PMID- 23532582
TI  - Water, water everywhere, but not a drop in sight: the impact of drug shortages on
      Canadian anesthesia care.

PMID- 23532583
TI  - Leaf litter quality affects aquatic insect emergence: contrasting patterns from
      two foundation trees.
AB  - Reciprocal subsidies between rivers and terrestrial habitats are common where
      terrestrial leaf litter provides energy to aquatic invertebrates while emerging
      aquatic insects provide energy to terrestrial predators (e.g., birds, lizards,
      spiders). We examined how aquatic insect emergence changed seasonally with litter
      from two foundation riparian trees, whose litter often dominates riparian streams
      of the southwestern United States: Fremont (Populus fremontii) and narrowleaf
      (Populus angustifolia) cottonwood. P. fremontii litter is fast-decomposing and
      lower in defensive phytochemicals (i.e., condensed tannins, lignin) relative to
      P. angustifolia. We experimentally manipulated leaf litter from these two species
      by placing them in leaf enclosures with emergence traps attached in order to
      determine how leaf type influenced insect emergence. Contrary to our initial
      predictions, we found that packs with slow-decomposing leaves tended to support
      more emergent insects relative to packs with fast-decomposing leaves. Three
      findings emerged. Firstly, abundance (number of emerging insects m(-2) day(-1))
      was 25% higher on narrowleaf compared to Fremont leaves for the spring but did
      not differ in the fall, demonstrating that leaf quality from two dominant trees
      of the same genus yielded different emergence patterns and that these patterns
      changed seasonally. Secondly, functional feeding groups of emerging insects
      differed between treatments and seasons. Specifically, in the spring collector
      gatherer abundance and biomass were higher on narrowleaf leaves, whereas
      collector-filterer abundance and biomass were higher on Fremont leaves. Shredder
      abundance and biomass were higher on narrowleaf leaves in the fall. Thirdly,
      diversity (Shannon's H') was higher on Fremont leaves in the spring, but no
      differences were found in the fall, showing that fast-decomposing leaves can
      support a more diverse, complex emergent insect assemblage during certain times
      of the year. Collectively, these results challenge the notion that leaf quality
      is a simple function of decomposition, suggesting instead that aquatic insects
      benefit differentially from different leaf types, such that some use slow
      decomposing litter for habitat and its temporal longevity and others utilize fast
      decomposing litter with more immediate nutrient release.

PMID- 23532584
TI  - The anisotropy1 D604N mutation in the Arabidopsis cellulose synthase1 catalytic
      domain reduces cell wall crystallinity and the velocity of cellulose synthase
      complexes.
AB  - Multiple cellulose synthase (CesA) subunits assemble into plasma membrane
      complexes responsible for cellulose production. In the Arabidopsis (Arabidopsis
      thaliana) model system, we identified a novel D604N missense mutation, designated
      anisotropy1 (any1), in the essential primary cell wall CesA1. Most previously
      identified CesA1 mutants show severe constitutive or conditional phenotypes such
      as embryo lethality or arrest of cellulose production but any1 plants are viable
      and produce seeds, thus permitting the study of CesA1 function. The dwarf mutants
      have reduced anisotropic growth of roots, aerial organs, and trichomes.
      Interestingly, cellulose microfibrils were disordered only in the epidermal cells
      of the any1 inflorescence stem, whereas they were transverse to the growth axis
      in other tissues of the stem and in all elongated cell types of roots and dark
      grown hypocotyls. Overall cellulose content was not altered but both cell wall
      crystallinity and the velocity of cellulose synthase complexes were reduced in
      any1. We crossed any1 with the temperature-sensitive radial swelling1-1 (rsw1-1)
      CesA1 mutant and observed partial complementation of the any1 phenotype in the
      transheterozygotes at rsw1-1's permissive temperature (21 degrees C) and full
      complementation by any1 of the conditional rsw1-1 root swelling phenotype at the
      restrictive temperature (29 degrees C). In rsw1-1 homozygotes at restrictive
      temperature, a striking dissociation of cellulose synthase complexes from the
      plasma membrane was accompanied by greatly diminished motility of intracellular
      cellulose synthase-containing compartments. Neither phenomenon was observed in
      the any1 rsw1-1 transheterozygotes, suggesting that the proteins encoded by the
      any1 allele replace those encoded by rsw1-1 at restrictive temperature.

PMID- 23532586
TI  - Microtubule dynamic instability: a new model with coupled GTP hydrolysis and
      multistep catastrophe.
AB  - A key question in understanding microtubule dynamics is how GTP hydrolysis leads
      to catastrophe, the switch from slow growth to rapid shrinkage. We first provide
      a review of the experimental and modeling literature, and then present a new
      model of microtubule dynamics. We demonstrate that vectorial, random, and coupled
      hydrolysis mechanisms are not consistent with the dependence of catastrophe on
      tubulin concentration and show that, although single-protofilament models can
      explain many features of dynamics, they do not describe catastrophe as a
      multistep process. Finally, we present a new combined (coupled plus random
      hydrolysis) multiple-protofilament model that is a simple, analytically solvable
      generalization of a single-protofilament model. This model accounts for the
      observed lifetimes of growing microtubules, the delay to catastrophe following
      dilution and describes catastrophe as a multistep process.

PMID- 23532588
TI  - High reliability of an algorithm for choice of implants in hip fracture patients.
AB  - PURPOSE: Hip fracture treatment is controversial, with high complication rates.
      An algorithm for hip fracture surgery has shown reduced reoperation rates, but
      choice of implant is based on the commonly used fracture classifications, which
      were previously evaluated to be unreliable. The purpose of this study was to
      investigate the reliability of the algorithm. METHODS: From two hospitals, four
      observers (orthopaedic consultant, fellow, resident and intern) used the
      algorithm to classify into 15 hip fracture types [Garden type I-IV femoral neck
      including posterior tilt, vertical femoral neck, basocervical and
      Arbeitsgemeinschaft fur Osteosynthesefragen (AO)-31 A1.1 to A3.3 trochanteric
      fractures] and to choose between five surgical procedures [parallel implants,
      prosthesis, two-or four-hole sliding hip screw (SHS) and intermedullary (IM)
      nail]. After individual assessment, each hospital made a consensus decision.
      Observations were performed twice, ten weeks apart, on pelvic, anteroposterior
      (AP) and axial X-rays from 100 consecutive patients. RESULTS: For fracture
      classification, mean kappa values were 0.60 for intra and 0.62 for interobserver
      variation, with interobserver variation between hospitals at 0.65. For posterior
      tilt, mean intraclass correlation coefficient was 0.91 for intra and 0.87 for
      interobserver variation. For choice of implant type, mean kappa values were 0.86
      for both intra and interobserver variation. The two hospital consensus decisions
      chose same implant in 91 of 100 patients, giving a kappa value at 0.88.
      CONCLUSION: Although hip fracture classification confirmed to be somewhat
      unreliable in this study, posterior tilt measurement and subsequent choice of
      implant type by the algorithm was found to be reliable, which opens up the
      possibility for a more standardized treatment of hip fracture patients between
      hospitals.

PMID- 23532587
TI  - Proteomic analysis of synovial fluid: insight into the pathogenesis of knee
      osteoarthritis.
AB  - PURPOSE: We conducted a proteomic analysis of synovial fluid (SF) to identify
      differentially expressed proteins and analyse their correlation with
      osteoarthritis (OA) severity. Our primary purpose was to gain insight into the
      pathogenesis of OA. METHODS: SF samples were acquired from 12 knee OA patients
      and 12 non-OA controls (ten had a meniscus injury, two had a discoid meniscus and
      all exhibited intact articular cartilage) and sequentially subjected to two
      dimensional electrophoresis (2-DE). The radiographic grading of knee OA was
      performed using the Kellgren-Lawrence criteria. Differentially expressed proteins
      were identified by matrix-assisted laser desorption/ionisation time-of
      flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Proteins of interest
      identified from SF were detected using an enzyme-linked immunosorbent assay
      (ELISA). RESULTS: A total of 31 protein spots showed significant differences (p <
      0.05) between the sample groups; 25 of the 31 spots (80.6 %) were identified as
      proteins of interest. Among them 20 corresponded to up-regulation and five to
      down-regulation in OA samples. HLA-DR was one of the proteins up-regulated, which
      was confirmed by ELISA. CONCLUSIONS: These observations have implications in
      delineating the protein expression underlying the pathogenesis of OA and
      facilitate further elucidation of molecular mechanisms involved in disease
      progression. Substantial alterations of the protein profile in SF may be
      associated with OA severity.

PMID- 23532589
TI  - Umbrella-shaped, memory alloy femoral head support device for treatment of
      avascular osteonecrosis of the femoral head.
AB  - PURPOSE: Avascular necrosis (AVN) of the femoral head is a common orthopaedic
      disease that is difficult to treat. The purpose of this study was to explore the
      preliminary efficacy of a self-designed umbrella-shaped memory alloy femoral head
      support device in the treatment of adult patients with avascular osteonecrosis of
      the femoral head. METHODS: The minimally-invasive approach involved curettage of
      the necrotic tissue of the femoral head, and a self-designed umbrella-shaped,
      memory alloy femoral head support device was implanted into the collapsed
      necrotic area to support the collapsed femoral head. Autologous iliac bone and
      artificial bone were implanted into the support device for the treatment of adult
      patients with avascular osteonecrosis of the femoral head. RESULTS: The clinical
      device was used in ten patients and 18 hip joints. The support device failed in
      one hip joint, which subsequently underwent joint replacement surgery, and the
      remaining 17 implanted devices were followed up for four to 19 months. The 17
      postoperative hip joints were evaluated using the percent-efficacy evaluation
      method for avascular osteonecrosis of the femoral head in adult patients, and the
      efficacy rate was 82.35 %. CONCLUSION: The umbrella-shaped femoral head support
      device can be used in Ficat stage I, stage II, and stage III adult patients with
      avascular osteonecrosis of the femoral head.

PMID- 23532591
TI  - An eye for relations: eye-tracking indicates long-term negative effects of
      operational thinking on understanding of math equivalence.
AB  - Prior knowledge in the domain of mathematics can sometimes interfere with
      learning and performance in that domain. One of the best examples of this
      phenomenon is in students' difficulties solving equations with operations on both
      sides of the equal sign. Elementary school children in the U.S. typically acquire
      incorrect, operational schemata rather than correct, relational schemata for
      interpreting equations. Researchers have argued that these operational schemata
      are never unlearned and can continue to affect performance for years to come,
      even after relational schemata are learned. In the present study, we investigated
      whether and how operational schemata negatively affect undergraduates'
      performance on equations. We monitored the eye movements of 64 undergraduate
      students while they solved a set of equations that are typically used to assess
      children's adherence to operational schemata (e.g., 3 + 4 + 5 = 3 + __).
      Participants did not perform at ceiling on these equations, particularly when
      under time pressure. Converging evidence from performance and eye movements
      showed that operational schemata are sometimes activated instead of relational
      schemata. Eye movement patterns reflective of the activation of relational
      schemata were specifically lacking when participants solved equations by adding
      up all the numbers or adding the numbers before the equal sign, but not when they
      used other types of incorrect strategies. These findings demonstrate that the
      negative effects of acquiring operational schemata extend far beyond elementary
      school.

PMID- 23532593
TI  - Polarization and reprogramming of myeloid-derived suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSC) have recently emerged as one of the
      central regulators of the immune system. In recent years, interest in
      understanding MDSC biology and applying MDSC for therapeutic purpose has exploded
      exponentially. Despite recent progress in MDSC biology, the mechanisms underlying
      MDSC development from expansion and activation to polarization in different
      diseases remain poorly understood. More recent studies have demonstrated that two
      MDSC subsets, M (monocytic)-MDSC and G (granulocytic)-MDSC, are able to polarize
      from a classically activated phenotype (M1) to an alternatively activated one
      (M2), or vice versa, in tumor-bearing mice. This phenotypic polarization affects
      MDSC function and disease progression. In this article, we summarize and discuss
      polarization, mechanism and therapeutic potential of MDSC. An emphasis is placed
      on the emerging concept of reprogramming MDSC polarization as a therapeutic
      strategy.

PMID- 23532592
TI  - Cross-frequency coupling within and between the human thalamus and neocortex.
AB  - There is currently growing interest in, and increasing evidence for, cross
      frequency interactions between electrical field oscillations in the brains of
      various organisms. A number of theories have linked such interactions to crucial
      features of neuronal function and cognition. In mammals, these interactions have
      mostly been reported in the neocortex and hippocampus, and it remains unexplored
      whether similar patterns of activity occur in the thalamus, and between the
      thalamus and neocortex. Here we use data recorded from patients undergoing
      thalamic deep-brain stimulation for epilepsy to demonstrate the existence and
      prevalence, across a range of frequencies, of both phase-amplitude (PAC) and
      amplitude-amplitude coupling (AAC) both within the thalamus and prefrontal cortex
      (PFC), and between them. These cross-frequency interactions may play an important
      role in local processing within the thalamus and neocortex, as well as
      information transfer between them.

PMID- 23532594
TI  - A phase I study of sorafenib in combination with S-1 plus cisplatin in patients
      with advanced gastric cancer.
AB  - BACKGROUND: Sorafenib inhibits several receptor tyrosine kinases involved in
      tumor progression and angiogenesis. S-1, an oral fluorouracil antitumor drug,
      plus cisplatin (CDDP) is the standard regimen for advanced gastric adenocarcinoma
      (AGC) in Japan. The purpose of this phase I study was to evaluate the safety,
      pharmacokinetics, and preliminary efficacy of sorafenib in combination with S-1
      plus CDDP. METHODS: Patients with histologically confirmed previously untreated
      AGC were evaluated for eligibility and treated with sorafenib (400 mg bid, days 1
      35), S-1 (40 mg/m(2) bid, days 1-21), and CDDP (60 mg/m(2), day 8). Treatment was
      continued until disease progression or unacceptable toxicity. Pharmacokinetics
      for sorafenib, 5-FU, and CDDP were investigated in cycle 1. RESULTS: Thirteen
      patients were enrolled and received at least one dose of the study treatment. No
      specific or serious adverse event was newly reported in this study. Five patients
      had partial response and 8 had stable disease as the best response.
      Pharmacokinetic analysis showed no significant differences in the exposures of
      sorafenib when administered alone or in combination with S-1 and CDDP.
      CONCLUSIONS: The present phase I study demonstrates the acceptable toxicity and
      preliminary efficacy of combined treatment with S-1, CDDP, and sorafenib.

PMID- 23532595
TI  - Doping in sport: a review of elite athletes' attitudes, beliefs, and knowledge.
AB  - Doping in sport is a well-known phenomenon that has been studied mainly from a
      biomedical point of view, even though psychosocial approaches are also key
      factors in the fight against doping. This phenomenon has evolved greatly in
      recent years, and greater understanding of it is essential for developing
      efficient prevention programmes. In the psychosocial approach, attitudes are
      considered an index of doping behaviour, relating the use of banned substances to
      greater leniency towards doping. The aim of this review is to gather and
      critically analyse the most recent publications describing elite athletes'
      attitudes, beliefs and knowledge of doping in sport, to better understand the
      foundations provided by the previous work, and to help develop practical
      strategies to efficiently combat doping. For this purpose, we performed a
      literature search using combinations of the terms "doping", "sport", "elite
      athletes", "attitudes", "beliefs", "knowledge", "drugs", and "performance
      enhancing substances" (PES). A total of 33 studies were subjected to
      comprehensive assessment using articles published between 2000 and 2011. All of
      the reports focused on elite athletes and described their attitudes, beliefs and
      knowledge of doping in sport. The initial reasons given for using banned
      substances included achievement of athletic success by improving performance,
      financial gain, improving recovery and prevention of nutritional deficiencies, as
      well as the idea that others use them, or the "false consensus effect". Although
      most athletes acknowledge that doping is cheating, unhealthy and risky because of
      sanctions, its effectiveness is also widely recognized. There is a general belief
      about the inefficacy of anti-doping programmes, and athletes criticise the way
      tests are carried out. Most athletes consider the severity of punishment is
      appropriate or not severe enough. There are some differences between sports, as
      team-based sports and sports requiring motor skills could be less influenced by
      doping practices than individual self-paced sports. However, anti-doping controls
      are less exhaustive in team sports. The use of banned substance also differs
      according to the demand of the specific sport. Coaches appear to be the main
      influence and source of information for athletes, whereas doctors and other
      specialists do not seem to act as principal advisors. Athletes are becoming
      increasingly familiar with anti-doping rules, but there is still a lack of
      knowledge that should be remedied using appropriate educational programmes. There
      is also a lack of information on dietary supplements and the side effects of PES.
      Therefore, information and prevention are necessary, and should cater to the
      athletes and associated stakeholders. This will allow us to establish and
      maintain correct attitudes towards doping. Psychosocial programmes must be
      carefully planned and developed, and should include middle- to long-term
      objectives (e.g. changing attitudes towards doping and the doping culture). Some
      institutions have developed or started prevention or educational programmes
      without the necessary resources, while the majority of the budget is spent on
      anti-doping testing. Controls are obviously needed, as well as more efficient
      educational strategies. Therefore, we encourage sporting institutions to invest
      in educational programmes aimed at discouraging the use of banned substances.
      Event organizers and sport federations should work together to adapt the rules of
      each competition to disincentivize dopers. Current research methods are weak,
      especially questionnaires. A combination of qualitative and quantitative
      measurements are recommended, using interviews, questionnaires and, ideally,
      biomedical tests. Studies should also examine possible geographical and cultural
      differences in attitudes towards doping.

PMID- 23532596
TI  - Unique cardiac Purkinje fiber transient outward current beta-subunit composition:
      a potential molecular link to idiopathic ventricular fibrillation.
AB  - RATIONALE: A chromosomal haplotype producing cardiac overexpression of dipeptidyl
      peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular
      fibrillation. The molecular basis of transient outward current (I(to)) in
      Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes
      to PF I(to) and that its overexpression might specifically alter PF I(to)
      properties and repolarization. OBJECTIVE: To assess the potential role of DPP6 in
      PF I(to). METHODS AND RESULTS: Clinical data in 5 idiopathic ventricular
      fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF
      and ventricular muscle I(to) had similar density, but PF I(to) differed from
      ventricular muscle in having tetraethylammonium sensitivity and slower recovery.
      DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced,
      I(to) density and tetraethylammonium sensitivity in canine PF but not in
      ventricular muscle cells. The K(+)-channel interacting beta-subunit K(+)-channel
      interacting protein type-2, essential for normal expression of I(to) in
      ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin
      (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in
      Chinese hamster ovary cells produced small I(to); I(to) amplitude was greatly
      enhanced by coexpression with K(+)-channel interacting protein type-2 or DPP6.
      Coexpression of DPP6 with Kv4.3 and K(+)-channel interacting protein type-2
      failed to alter I(to) compared with Kv4.3/K(+)-channel interacting protein type-2
      alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF
      I(to) composition) greatly enhanced I(to) compared with Kv4.3/neuronal calcium
      sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties.
      A mathematical model of cardiac PF action potentials showed that I(to)
      enhancement can greatly accelerate PF repolarization. CONCLUSIONS: These results
      point to a previously unknown central role of DPP6 in PF I(to), with DPP6 gain of
      function selectively enhancing PF current, and suggest that a DPP6-mediated PF
      early-repolarization syndrome might be a novel molecular paradigm for some forms
      of idiopathic ventricular fibrillation.

PMID- 23532598
TI  - Family obligation values and family assistance behaviors: protective and risk
      factors for Mexican-American adolescents' substance use.
AB  - Adolescent substance use is one of today's most important social concerns, with
      Latino youth exhibiting the highest overall rates of substance use. Recognizing
      the particular importance of family connection and support for families from
      Mexican backgrounds, the current study seeks to examine how family obligation
      values and family assistance behaviors may be a source of protection or risk for
      substance use among Mexican-American adolescents. Three hundred and eighty-five
      adolescents (51% female) from Mexican backgrounds completed a questionnaire and
      daily diary for 14 consecutive days. Results suggest that family obligation
      values are protective, relating to lower substance use, due, in part, to the
      links with less association with deviant peers and increased adolescent
      disclosure. In contrast, family assistance behaviors are a source of risk within
      high parent-child conflict homes, relating to higher levels of substance use.
      These findings suggest that cultural values are protective against substance use,
      but the translation of these values into behaviors can be a risk factor depending
      upon the relational context of the family.

PMID- 23532597
TI  - Focal energy deprivation underlies arrhythmia susceptibility in mice with calcium
      sensitized myofilaments.
AB  - RATIONALE: The Ca(2+) sensitivity of the myofilaments is increased in
      hypertrophic cardiomyopathy and other heart diseases and may contribute to a
      higher risk for sudden cardiac death. Ca(2+) sensitization increases
      susceptibility to reentrant ventricular tachycardia in animal models, but the
      underlying mechanism is unknown. OBJECTIVE: To investigate how myofilament Ca(2+)
      sensitization creates reentrant arrhythmia susceptibility. METHODS AND RESULTS:
      Using hypertrophic cardiomyopathy mouse models (troponinT-I79N) and a Ca(2+)
      sensitizing drug (EMD57033), here we identify focal energy deprivation as a
      direct consequence of myofilament Ca(2+) sensitization. To detect ATP depletion
      and thus energy deprivation, we measured accumulation of dephosphorylated
      Connexin 43 (Cx43) isoform P0 and AMP kinase activation by Western blotting and
      immunostaining. No differences were detected between groups at baseline, but
      regional accumulation of Connexin 43 isoform P0 occurred within minutes in all
      Ca(2+)-sensitized hearts, in vivo after isoproterenol challenge and in isolated
      hearts after rapid pacing. Lucifer yellow dye spread demonstrated reduced gap
      junctional coupling in areas with Connexin 43 isoform P0 accumulation. Optical
      mapping revealed that selectively the transverse conduction velocity was slowed
      and anisotropy increased. Myofilament Ca(2+) desensitization with blebbistatin
      prevented focal energy deprivation, transverse conduction velocity slowing, and
      the reentrant ventricular arrhythmias. CONCLUSIONS: Myofilament Ca(2+)
      sensitization rapidly leads to focal energy deprivation and reduced intercellular
      coupling during conditions that raise arrhythmia susceptibility. This is a novel
      proarrhythmic mechanism that can increase arrhythmia susceptibility in
      structurally normal hearts within minutes and may, therefore, contribute to
      sudden cardiac death in diseases with increased myofilament Ca(2+) sensitivity.

PMID- 23532599
TI  - Chronic use of PPI and H2 antagonists decreases the risk of pouchitis after IPAA
      for ulcerative colitis.
AB  - INTRODUCTION: Bacteria have been implicated in the development of pouchitis after
      ileal pouch anal anastomosis. The change in gastric pH with the use of proton
      pump inhibitors and H(2) antagonists may lead to alteration of enteric bacteria.
      We hypothesized that chronic use of these medications would decrease the
      incidence of pouchitis. METHODS: Patients who had undergone ileal pouch anal
      anastomosis for ulcerative colitis were classified by history of pouchitis.
      Patients were further classified by their use of proton pump inhibitors, H(2)
      blockers, antacids, and other known risk factors for pouchitis. RESULTS: Eighty
      five patients were identified. There was a statistically significant increase in
      the use of daily acid suppression in patients without pouchitis. There was also a
      statistically significant increase in the use of antacids in patients without
      pouchitis. Occasional use of acid suppression did not alter the rate of
      pouchitis. CONCLUSIONS: Our data suggest that the daily use of proton pump
      inhibitors, H(2) antagonists, or antacids is associated with a decreased risk of
      pouchitis in ulcerative colitis. Occasional use of these agents did not seem to
      afford the same protection. These data suggest that altering the pH of the
      gastrointestinal tract may influence the development of pouchitis.

PMID- 23532601
TI  - Outcome of patients with aggressive pseudomyxoma peritonei treated by
      cytoreductive surgery and intraperitoneal chemotherapy.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an incidence rate
      of approximately 1 per million a year. During the past few years, there has been
      a survival benefit for these patients treated by complete cytoreduction and
      perioperative chemotherapy. Better survival rates were found in the
      adenomucinosis group than the carcinomatosis group. The purpose of our study was
      to analyze the outcome and the prognosis factors of only high-grade PMP. METHODS:
      We selected 38 patients from a prospective database of 59 with high-grade PMP
      from appendiceal origin who were treated by cytoreduction surgery and HIPEC at
      the Hospital University Reina Sofia (Cordoba, Spain) between 1998 and July 2012.
      Clinical, surgical, analytical, radiological, and histological data were obtained
      prospectively. Survival curves were calculated using the Kaplan-Meier method, a
      univariate analysis was performed and the log rank-test was used to analyze the
      effects of several clinical and pathologic factors on overall survival (OS) and
      disease-free survival (DFS). RESULTS: Median follow-up time was 32 months (range,
      2-170). Median age at diagnosis was 57 years (range, 32-77). In 89.5 % of
      patients, optimal cytoreduction CC-0 (57.9 %) and CC-1 (31.6 %) was achieved. In
      the remaining 10.5 %, cytoreduction was classified as CC-2. The median PCI score
      was 21 (range, 4-38). Morbidity complications >= Grade 3 in the CTCAE v 3.0
      classification was 18.4 %. One patient died 45 days postsurgery. Median OS at the
      end of follow-up was 36 months (range, 9-83); overall 5-year survival rate was
      58.7 %. In the univariate analysis for OS, significant values were obtained for
      lymph-node involvement and suboptimal cytoreduction. The 5-year OS was 64.5 %
      when an optimal cytoreduction was achieved. Median DFS was 36 months (17-54); 3
      year DFS rate was 49.1 %. Neoadjuvant therapy did not affect the survival of
      these patients; there was no difference in the 5-year OS (43 % vs. 75 %, p =
      0.068). CONCLUSIONS: In aggressive PMP, cytoreduction with peritonectomy
      procedure plus HIPEC is a safe procedure that suggests an improvement to the
      survival rates. Because optimal cytoreduction is a primary prognostic factor for
      survival rates, this procedure would have to be performed in an experienced
      center with a low morbidity. Neoadjuvant chemotherapy has not demonstrated
      benefits in these patients and further research will be required.

PMID- 23532602
TI  - Does preoperative 25-hydroxyvitamin D status significantly affect the calcium
      kinetics after total thyroidectomy?
AB  - BACKGROUND: Although previous studies have suggested that low preoperative 25
      hydroxyvitamin D (25-OHD) is a risk factor for hypocalcemia after total
      thyroidectomy, the impact of preoperative 25-OHD on calcium (Ca)/parathyroid
      hormone (PTH) kinetics in the immediate postoperative period remains unclear. The
      study compared the postoperative Ca/PTH kinetics between different preoperative
      25-OHD levels. PATIENTS: A total of 281 patients who underwent a total
      thyroidectomy were analyzed. Serum Ca was measured preoperatively within 1 h
      after surgery (Ca-D0) and on the following morning (Ca-D1). Preoperative 25-OHD
      was also measured after overnight fasting while postoperative PTH was checked at
      skin closure on day 0 (PTH-D0) and on the following morning on day 1 (PTH-D1).
      The Ca/PTH kinetics were compared between three groups (group I: preoperative 25
      OHD < 10 ng/mL; group II: 25-OHD = 10-20 ng/mL; group III: 25-OHD > 20 ng/mL).
      RESULTS: Group I had significantly lower preoperative Ca (p = 0.016) and Ca-D0 (p
      = 0.036) but higher PTH-D1 (p = 0.015) than groups II and III. PTH-D0, Ca-D1, and
      the rate of clinically significant hypocalcemia were similar in the three groups.
      Group I had a significantly smaller Ca drop (-0.02 vs. 0.01 and 0.02 mmol/L, p =
      0.011) and a tendency for a significantly smaller PTH drop (0.4 vs. 0.5 and 1.0
      pmol/L, p = 0.073) than groups II and III. PTH-D1 (OR = 1.550) and 25-OHD (OR =
      0.958) were independent factors for Ca drop from day 0 to day 1. CONCLUSIONS:
      Although group I began with lower serum Ca, those patients tended to have a
      greater PTH response to Ca drop and so preoperative 25-OHD did not significantly
      affect the overall Ca kinetics from preoperative to day 1.

PMID- 23532603
TI  - High levels of lung resident CD4+CD28null cells in COPD: implications of
      autoimmunity.
AB  - Chronic obstructive pulmonary disease (COPD) is a worldwide burden and a major
      cause of death. Pathogenetic mechanisms underlying the disease are still largely
      unknown. However, a continuous toxic injury due to tobacco smoking leading to a
      self-maintaining inflammatory process is considered a key factor in the
      pathophysiology of the disease. Evidence that autoimmunity might be involved in
      the maintenance of COPD has been recently noticed with great interest.During the
      chronic phase of an autoimmune response, lymphocytes lose their costimulatory
      signals. Previously, CD4+CD28null cells were reported to be systemically
      heightened in COPD patients. However, a direct role of CD4+CD28null cells in the
      pathogenesis of COPD is still under discussion, since there is no evidence that
      CD4+CD28null cells originate from the lungs of diseased patients. Therefore, we
      evaluated lungs from end-stage COPD patients and compared the levels of tissue
      infiltrating CD4+CD28null cells to systemic levels. We could show that
      CD4+CD28null cells are present in high amounts in lung tissue obtained from COPD
      GOLD IV patients suggesting a direct involvement of those cells in the
      pathophysiology of COPD. Furthermore, purified lung-resident CD4+ cells showed a
      stable proliferative response to lung specific elastin and collagen.These results
      further corroborate the role of autoreactive CD4+ cells in the maintenance of the
      inflammatory destruction in COPD. Modulating CD4+ cell function might be a new
      promising tool for future therapeutic approaches.

PMID- 23532600
TI  - The role of glutamate and the immune system in organophosphate-induced CNS
      damage.
AB  - Organophosphate (OP) poisoning is associated with long-lasting neurological
      damage, which is attributed mainly to the excessive levels of glutamate caused by
      the intoxication. Glutamate toxicity, however, is not specific to OP poisoning,
      and is linked to propagation of damage in both acute and chronic
      neurodegenerative conditions in the central nervous system (CNS). In addition to
      acute excitotoxic effects of glutamate, there is now a growing amount of evidence
      of its intricate immunomodulatory effects in the brain, involving both the innate
      and the adaptive immune systems. Moreover, it was demonstrated that
      immunomodulatory treatments, aimed at regulating the interaction between the
      resident immune cells of the brain (microglia) and the peripheral immune system,
      can support buffering of excessive levels of glutamate and restoration of the
      homeostasis. In this review, we will discuss the role of glutamate as an
      excitotoxic agent in the acute phase of OP poisoning, and the possible functions
      it may have as both a neuroprotectant and an immunomodulator in the sub-acute and
      chronic phases of OP poisoning. In addition, we will describe the novel immune
      based neuroprotective strategies aimed at counteracting the long-term
      neurodegenerative effects of glutamate in the CNS. 

PMID- 23532604
TI  - [Medical University of Vienna Researcher of the Month of March 2013].

PMID- 23532607
TI  - Nicotinamide N-methyltransferase in non-small cell lung cancer: promising results
      for targeted anti-cancer therapy.
AB  - Lung cancer, predominantly non-small cell lung cancer (NSCLC), is currently the
      most common cause of malignancy-related death in the world. Despite advances in
      both detection and treatment, its incidence rate is still increasing. Therefore,
      effective strategies for early detection as well as molecular therapeutic targets
      are urgently needed. We focused on the enzyme nicotinamide N-methyltransferase
      (NNMT). NNMT expression levels were investigated in tumor, tumor-adjacent, and
      surrounding tissue samples of 25 patients with NSCLC by Real-Time PCR, Western
      blot analysis, and catalytic activity assay. NNMT enzyme activity in NSCLC was
      then correlated with clinicopathological characteristics. Results obtained showed
      NNMT upregulation (mRNA and protein) in tumor compared with both tumor-adjacent
      and surrounding tissue. Moreover, NSCLC displayed significantly higher activity
      levels than those determined in both tumor-adjacent and surrounding tissue.
      Interestingly, both tumor-adjacent and surrounding tissue samples of unfavorable
      cases (N+) seem to display higher activity levels than those of favorable NSCLCs
      (N0). The present work shows a marked increase of NNMT enzyme activity in NSCLC
      and suggests that normal-looking tissue of unfavorable cases seems to change
      toward cancer. Further studies may establish whether NNMT could represent a
      target for an effective anti-cancer therapy. 

PMID- 23532608
TI  - Classifying the stage IV colorectal cancer: prognostic impact of radical
      resection for colorectal liver metastases and proposal for a new staging system.
AB  - Currently, there is no universally accepted system to classify the stage IV
      colorectal cancer. Here, we analyze the prognostic impact of radical resection
      for colorectal liver metastases and propose a new staging system for stage IV
      colorectal cancer. A retrospective review was undertaken of 126 consecutive
      patients who underwent surgical treatment for colorectal liver metastases from
      January 1997 to January 2004. Based on the overall survival rates (Kaplan-Meier
      method) and surgical outcomes, we propose a new staging system for stage IV
      colorectal cancer. Patients were divided into two groups: patients who underwent
      initial hepatic resections (R0 resection) for liver metastases (group 1, n = 22),
      and patients who underwent palliative resection for unresectable liver metastases
      (group 2, n = 104). The overall survival rates in group 1 at 1, 3, and 5 years
      were 68.2% (15/22), 40.9% (9/22), and 18.2% (4/22), respectively. The overall
      survival rates in group 2 at 1, 3, and 5 years were 54.8% (57/104), 16.3%
      (17/104), and 0% (0/104), respectively. There was a significant difference in
      overall survival rates between both groups (p < 0.05). Based on the study
      results, we propose a new staging system where all distant metastases are grouped
      within stage IV and subclassified into resectable (R0 resection) and unresectable
      stages. Curative surgical treatment is a critical prognostic factor in colorectal
      liver metastases. The proposed new staging system for stage IV colorectal cancer
      is simple and is clinically useful to estimate the prognosis.

PMID- 23532609
TI  - Endoscopic approach for the treatment of pineal region tumors.
AB  - Tumors of the pineal region account for 3 to 8% of the tumors involving the
      central nervous system. The most common are germ cell tumors (39%). Less common
      examples include teratomas, primitive neuroectodermic tumors, astrocytomas, and
      choriocarcinomas. Clinical presentation in pediatric patients is in direct
      relation to the anatomical structures surrounding the pineal region and to the
      associated hydrocephalus that is present in almost 90% of cases. The diagnosis of
      a tumor in the pineal region is based on radiological findings and the presence
      of tumor markers such as alpha-fetoprotein and human chorionic gonadotrophic
      hormone subfraction beta. Neuroendoscopy is considered to be one of the minimally
      invasive techniques useful for the management of such patients. This minimally
      invasive approach to pineal region tumors allows the treatment of hydrocephalus
      in a safe and effective way, avoiding the complications derived from other
      procedures such as external ventricular drainage or shunt surgery. 

PMID- 23532610
TI  - How to minimize ischemic complication related to swollen temporalis muscle
      following indirect revascularization surgery in moyamoya disease: a technical
      report.
AB  - BACKGROUND: There are several reports in the literature of postoperative ischemic
      events due to swelling of the temporalis muscle after indirect revascularization
      surgery. Here, we report our surgical technique for preventing ischemic events
      during the acute postoperative recovery period in moyamoya patients. MATERIAL AND
      METHODS: We used various types of titanium mesh to cover the bony defect area in
      8 patients (10 operations) with moyamoya disease. The mesh was cut and
      manipulated according to the shape of the bony defect. RESULTS: Surgical results
      were favorable, with no newly developed ischemic event or infarction in the acute
      recovery period. The mesh formed an outer table of skull, so there was no
      compressive effect on the temporalis muscle and no cosmetic defects. CONCLUSIONS:
      The titanium mesh appears to be effective and useful for prevention of ischemic
      insult in the treatment of moyamoya disease. The choice of this procedure depends
      on both the operative findings of temporalis muscle thickness and the status of
      ischemic vulnerability of moyamoya brain.

PMID- 23532611
TI  - Complex reconstruction of the sella using absorbable mini-plate in revision
      endoscopic pituitary surgery: technical note.
AB  - BACKGROUND: Skull base reconstruction in the setting of revision endoscopic
      pituitary surgery with intraoperative cerebrospinal fluid (CSF) leak represents a
      unique challenge. MATERIALS AND METHODS: The demographics and outcomes of four
      patients undergoing revision endoscopic pituitary surgery with high-volume
      intraoperative CSF leak are described. The "gasket-seal" technique of sellar
      repair using bioabsorbable mini-plate is described. RESULTS: The indications for
      surgery were macroadenoma with suprasellar extension and optic nerve compression
      in three patients and growth hormone-secreting tumor in one patient with
      acromegaly. The multilayered reconstruction consisted of autologous fat placed in
      the tumor cavity followed by reconstruction of the sellar floor with an oversized
      sheet of either fascia lata or acellular dermal matrix placed over the skull base
      defect and sunken into the sella with a bioabsorbable mini-plate. One patient
      experienced postoperative CSF leak on postoperative day 2 that resolved with
      lumbar drainage alone. All patients were noted to have a well mucosalized
      sphenoid sinus and were free of CSF leak at last follow-up. CONCLUSION: Sellar
      reconstruction following endoscopic pituitary surgery represents a technical
      challenge, especially in revision cases with high-volume intraoperative CSF leak.
      The early experience with the "gasket-seal" closure using the bioabsorbable mini
      plate appears favorable. Lumbar drain may be indicated in patients with
      postoperative CSF leak.

PMID- 23532612
TI  - The international forum of ophthalmic simulation: developing a virtual reality
      training curriculum for ophthalmology.
AB  - BACKGROUND: To investigate the effect of a structured, supervised, cataract
      simulation programme on ophthalmic surgeons in their first year of training, and
      to evaluate the level of skill transfer. METHODS: Trainees with minimal
      intraocular and simulator experience in their first year of ophthalmology
      undertook a structured, sequential, customised, virtual reality (VR) cataract
      training programme developed through the International Forum of Ophthalmic
      Simulation. A set of one-handed, bimanual, static and dynamic tasks were
      evaluated before and after the course and scores obtained. Statistical
      significance was evaluated with the Wilcoxon sign-rank test. RESULTS: The median
      precourse score of 101.50/400 (IQR 58.75-145.75) was significantly improved after
      completing the training programme ((postcourse score: 302/400, range: 266.25
      343), p<0.001). While improvement was evident and found to be statistically
      significant in all parameters, greatest improvements were found for capsulorhexis
      and antitremor training ((Capsulorhexis: precourse score=0/100, range 0-4.5;
      postcourse score=81/100, range 13-87.75; p=0.002), (antitremor training:
      precourse score=0/100, range 0-0; postcourse score=80/100, range 60.25-91.50;
      p=0.001)). CONCLUSIONS: Structured and supervised VR training can offer a
      significant level of skills transfer to novice ophthalmic surgeons. VR training
      at the earliest stage of ophthalmic surgical training may, therefore, be of
      benefit.

PMID- 23532613
TI  - Intravitreal dexamethasone for central retinal vein occlusion with low visual
      acuity: a retrospective study.

PMID- 23532614
TI  - Femtosecond laser and microkeratome-assisted Descemet stripping endothelial
      keratoplasty: first clinical results.
AB  - AIM: To perform Descemet stripping automated endothelial keratoplasty (DSAEK)
      using a novel technique to obtain very thin (<100 um) posterior corneal disks.
      METHODS: Twenty five DSAEK grafts were prepared with two sequential cuts: the
      first cut, of variable thickness, was made with a femtosecond laser and the
      second with a 300 um microkeratome head. Spectacle corrected visual acuity,
      endothelial cell density evaluation with specular microscopy and anterior segment
      optical coherence tomography to measure central and peripheral graft thickness
      was performed preoperatively and postoperatively at 1, 3 and 6 months. RESULTS:
      There were no irregular cuts or perforations during tissue preparation. Central
      graft thickness was 79.6 um (SD +/- 14.5; range 54-98) and 69.3 um (SD +/- 14.2;
      range 49-96) at 3 and 6 months. Corrected distance visual acuity improved from
      0.91 logMAR preoperatively to 0.11 logMAR at 6 months. Donor endothelial cells
      averaged 2675 cells/mm(2) preoperatively and 1729 cells/mm(2) at 6 months. There
      were no graft detachments. CONCLUSIONS: This new technique consistently yielded
      very thin grafts (<100 um), excellent visual acuity results and good endothelial
      cell counts. No donor tissue was wasted.

PMID- 23532615
TI  - Macular choroidal blood flow velocity decreases with regression of acute central
      serous chorioretinopathy.
AB  - AIM: To quantitatively evaluate the time course of macular choroidal blood flow
      velocity in acute central serous chorioretinopathy (CSC). METHODS: This
      retrospective observational case series included 21 eyes of 20 patients (17 men,
      3 women; mean age, 53.0 years) with treatment-naive acute CSC. Laser speckle
      flowgraphy was performed to calculate macular mean blur rate (MBR), an indicator
      of relative blood flow velocity at the first visit, 3 and 6 months thereafter.
      Changes in average MBR values were compared with visual improvement at 6 months.
      RESULTS: Subretinal fluid completely resolved in all eyes within 6 months, while
      best-corrected visual acuity (BCVA) significantly improved at 6 months compared
      to the initial BCVA. During the follow-up period, the average MBR significantly
      decreased to 92.8% and 82.3% at 3 and 6 months, respectively, against baseline
      (100%). Importantly, there was a negative correlation between the BCVA recovery
      and the MBR decrease, showing the possible association of MBR increase with poor
      visual prognosis. Multiple regression analysis demonstrated no significant
      correlation between MBR and ocular perfusion pressure. CONCLUSIONS: These results
      indicate that macular choroidal blood flow velocity decreases concurrently with
      regression of CSC, suggesting a validity of choroidal blood flow elevation in the
      pathogenesis of acute CSC.

PMID- 23532616
TI  - Is indocyanine green angiography useful for the diagnosis of macular
      telangiectasia type 2?

PMID- 23532617
TI  - Near-infrared transillumination photography of intraocular tumours.
AB  - PURPOSE: To present a technique for near-infrared transillumination imaging of
      intraocular tumours based on the modifications of a conventional digital slit
      lamp camera system. METHODS: The Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit
      AG) was used for transillumination photography by gently pressing the tip of the
      background illumination cable against the surface of the patient's eye. Thus the
      light from the flash unit was transmitted into the eye, leading to improved
      illumination and image resolution. The modification for near-infrared photography
      was done by replacing the original camera with a Canon EOS 30D (Canon Inc)
      converted by Advanced Camera Services Ltd. In this camera, the infrared blocking
      filter was exchanged for a 720 nm long-pass filter, so that the near-infrared
      part of the spectrum was recorded by the sensor. RESULTS: The technique was
      applied in eight patients: three with anterior choroidal melanoma, three with
      ciliary body melanoma and two with ocular pigment alterations. The good
      diagnostic quality of the photographs made it possible to evaluate the exact
      location and extent of the lesions in relation to pigmented intraocular landmarks
      such as the ora serrata and ciliary body. The photographic procedure did not lead
      to any complications. CONCLUSIONS: We recommend near-infrared transillumination
      photography as a supplementary diagnostic tool for the evaluation and
      documentation of anteriorly located intraocular tumours.

PMID- 23532618
TI  - Orthovoltage radiotherapy in the management of medial canthal basal cell
      carcinoma.
AB  - AIMS: To report the local control and complication rates of orthovoltage
      radiotherapy in the management of medial canthal basal cell carcinoma (BCC).
      METHODS: The medical records of all patients treated with medial canthal BCC
      between 1998 and 2010, with orthovoltage radiotherapy as primary treatment,
      adjuvant treatment after incomplete surgical excision, or for tumour recurrence
      following surgical excision, were retrospectively studied. The actuarial rates of
      tumour control and complications were calculated using Kaplan-Meier estimates.
      Main outcome measures were rates of tumour control and radiation complications.
      RESULTS: 90 patients were included with a median follow-up of 80 months. Tumour
      control rate at 10 years for the entire cohort was 94% (95% CI 84% to 98%).
      Tumour control rates showed no statistically significant differences among
      different treatment intents or treatment radiation energies. Radiation-related
      complication rates included loss of eyelashes in 59% (95% CI 48% to 66%),
      epiphora 51% (95% CI 39% to 62%), dry eye 14% (95% CI 3% to 35%) and conjunctival
      scarring 11% (95% CI 1% to 33%). No patient developed long-term corneal
      complications. CONCLUSIONS: Orthovoltage radiotherapy can be a reliable
      therapeutic alternative for selected medial canthal BCCs, which can be contained
      within the prescribed radiation field, with anticipated radiation-related
      toxicities.

PMID- 23532619
TI  - How do tougher immigration measures affect unauthorized immigrants?
AB  - The recent impetus of tougher immigration-related measures passed at the state
      level raises concerns about the impact of such measures on the migration
      experience, trajectory, and future plans of unauthorized immigrants. In a recent
      and unique survey of Mexican unauthorized immigrants interviewed upon their
      voluntary return or deportation to Mexico, almost a third reported experiencing
      difficulties in obtaining social or government services, finding legal
      assistance, or obtaining health care services. Additionally, half of these
      unauthorized immigrants reported fearing deportation. When we assess how the
      enactment of punitive measures against unauthorized immigrants, such as E-Verify
      mandates, has affected their migration experience, we find no evidence of a
      statistically significant association between these measures and the difficulties
      reported by unauthorized immigrants in accessing a variety of services. However,
      the enactment of these mandates infuses deportation fear, reduces interstate
      mobility among voluntary returnees during their last migration spell, and helps
      curb deportees' intent to return to the United States in the near future.

PMID- 23532620
TI  - Deficits in high- (>60 Hz) gamma-band oscillations during visual processing in
      schizophrenia.
AB  - Current theories of the pathophysiology of schizophrenia have focused on abnormal
      temporal coordination of neural activity. Oscillations in the gamma-band range
      (>25 Hz) are of particular interest as they establish synchronization with great
      precision in local cortical networks. However, the contribution of high gamma
      (>60 Hz) oscillations toward the pathophysiology is less established. To address
      this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated
      patients with chronic schizophrenia and 16 controls during the perception of
      Mooney faces. MEG data were analysed in the 25-150 Hz frequency range. Patients
      showed elevated reaction times and reduced detection rates during the perception
      of upright Mooney faces while responses to inverted stimuli were intact. Impaired
      processing of Mooney faces in schizophrenia patients was accompanied by a
      pronounced reduction in spectral power between 60-120 Hz (effect size: d = 1.26)
      which was correlated with disorganized symptoms (r = -0.72). Our findings
      demonstrate that deficits in high gamma-band oscillations as measured by MEG are
      a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting
      an important aspect of the pathophysiology of the disorder.

PMID- 23532621
TI  - Changes in gonadal gene network by exogenous ligands in temperature-dependent sex
      determination.
AB  - We examined the expression of candidate sex-determining genes in the red-eared
      slider turtle (Trachemys scripta) during the temperature-sensitive period (TSP).
      Aromatase and Rspo1 were used as markers of ovarian differentiation and Sox9 was
      used as a marker of testicular differentiation. Eggs were incubated at a male
      producing temperature (26  degrees C or MPT) and a female-producing temperature
      (31  degrees C or FPT). First, eggs at the beginning of the TSP (stage 16) were
      topically treated with the steroid hormones 17beta-estradiol (E2), testosterone
      in combination with aromatase inhibitor (AI+T), the E2 antagonist (ICI 182 780),
      and the androgen antagonist (flutamide). Secondly, gonads were removed at stage
      16 and treated in vitro with E2, AI+T, or hormone antagonists. At the FPT, AI+T
      in ovo suppressed aromatase and Rspo1, while activating Sox9. At the MPT, E2
      treatment rapidly increased aromatase and Rspo1, while suppressing Sox9.
      Treatment with the E2 antagonist in ovo decreased aromatase at the FPT. Treatment
      with the androgen antagonist in ovo increased aromatase and Rspo1 at early time
      points at MPT and decreased Sox9 at MPT at later developmental stages. Treatment
      of isolated gonads cultured in vitro with AI+T at FPT decreased aromatase and
      Rspo1 and E2 increased the expression of these genes at MPT. In vitro treatment
      with E2 antagonist suppressed aromatase and Rspo1 expression at FPT. Overall, our
      results suggest that exogenous ligands dictate gonadal development by redirecting
      the expression of candidate sex-determining genes within the genetic cascades
      induced by temperature.

PMID- 23532622
TI  - Intracellular Enhanced Cyan Fluorescent Protein/Angiotensin II Does Not Modify
      Angiotensinogen Accumulation in Transgenic Mice.
AB  - BACKGROUND: Several studies suggest that extracellular angiotensin can upregulate
      renin and angiotensinogen (AGT). We have shown that enhanced cyan fluorescent
      protein/angiotensin II (ECFP/AngII) transgenic mice, in which AngII is fused
      downstream of ECFP and regulated by the mouse metallothionein housekeeping gene,
      possess elevated blood pressure and kidney thrombotic microangiopathy. The
      present study evaluated the effect of intracellular AngII on AGT messenger RNA
      (mRNA) and protein levels in ECFP/AngII transgenic mice. METHODS: The traditional
      guanidinium thiocyanate method was used to extract total mRNA. Proteins were
      extracted by homogenization in a tissue extraction reagent buffer. Northern blots
      for AGT mRNA and an 18S ribosomal RNA control were performed. Immunoblots for AGT
      protein levels with actin and tubulin controls were evaluated. RESULTS: Northern
      blot densitometry showed liver mRNA levels an average of 12-fold greater than
      levels in the brain or kidney in both Lines A and D (different copies of the
      transgene) with no quantifiable differences between wild-type (WT) and homozygous
      (HO) transgenic mice. Immunoblots showed liver AGT protein levels 3.2-fold
      greater than levels in the brain or kidney, with no differences observed between
      WT and HO transgenic mice. CONCLUSION: ECFP/AngII transgene expression does not
      alter AGT mRNA or protein levels in major organs (kidney, liver, and brain) of
      transgenic mice. The altered blood pressure and kidney thrombosis observed in
      these transgenic mouse lines are not the result of increased intracellular AGT
      synthesis and resultant increases in free extracellular AngII. This finding is
      consistent with our published studies that indicate no increase in circulating
      AngII by radioimmunoassay.

PMID- 23532624
TI  - A validated and stability indicating HPLC method for analysis of diminazene
      aceturate and antipyrine combination in a ready injectable solution.
AB  - Diminazene aceturate and Antipyrine combination therapy is widely used in
      veterinary medicine. A simple reverse HPLC method for the analysis of samples of
      a ready injectable formulation containing a mixture of active ingredients and
      inactive excipients has been developed. The HPLC analysis was carried out using a
      reversed phase (RP)-C18 (250 mm*4.0 mm, 5 MUm) column. The isocratic mobile phase
      consisted of a mixture of acetonitrile, methanol, phosphate buffer and hexane
      sulfonate; the flow rate was 0.6 mL/min and ultraviolet detection was at 291 nm.
      This method was validated in accordance with FDA and ICH guidelines and showed
      good linearity, accuracy, precision, selectivity and the system suitability
      results were within the acceptance criteria. A stability-indicating study was
      also carried out and indicated that this method could be used for purity and
      degradation evaluation of these formulations. 

PMID- 23532625
TI  - Induction of inflammation, DNA damage and apoptosis in rat heart after oral
      exposure to zinc oxide nanoparticles and the cardioprotective role of alpha
      lipoic acid and vitamin E.
AB  - Although zinc oxide nanoparticles (ZnO-NP) are being used on a wide scale in the
      world consumer market, their potential hazards on humans remain largely unknown.
      The present study was aimed at investigating the oral toxicity of ZnO-NP in 2
      dose regimen (600 mg/kg and 1 g/kg body weight for 5 consecutive days) in rats.
      In addition, the protective role of either alpha-lipoic acid (Lipo) or vitamin E
      (Vit E) against this cardiotoxic effect of ZnO-NPs was assessed. Results revealed
      that, co-administration of Lipo (200 mg/Kg body weight) or Vit E (100 mg/Kg body
      weight) daily for 3 weeks to rats intoxicated with ZnO-NPs (in either of the 2
      dose regimen) significantly ameliorated the cardiotoxic effect of these
      nanoparticles. As, both agents significantly reduced the increase in serum
      cardiac injury markers including troponin-T, creatine kinase-MB (CK-MB), and
      myoglobin. Additionally, Lipo and Vit E significantly decreased the increase in
      serum pro-inflammatory biomarkers level including tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). Moreover, either
      of the 2 used agents successfully alleviated the alteration in nitric oxide (NO)
      and vascular endothelial growth factor (VEGF) in ZnO-NPs in sera of intoxicated
      group. They also significantly reduced the increase in cardiac calcium
      concentration and the consequent oxidative deoxyribonucleic acid (DNA) damage, as
      well as the increase in cardiac caspase-3 activity of intoxicated rats.
      Conclusively, these results indicate that early treatment with either alpha
      lipoic acid or vitamin E may offer protection against cardiac tissue injury
      induced by the deleterious toxic impacts of ZnO-NPs.

PMID- 23532623
TI  - Body temperature during hibernation is highly correlated with a decrease in
      circulating innate immune cells in the brown bear (Ursus arctos): a common
      feature among hibernators?
AB  - BACKGROUND: Hibernation involves periods of severely depressed metabolism
      (torpor) and decreases in body temperature (Tb). Small arctic mammals (<5kg), in
      which Tb generally drop drastically, display leukopenia during hibernation. This
      raised the question of whether the decreased leukocyte counts in mammalian
      hibernators is due to torpor per se or is secondary to low Tb. The present study
      examined immune cell counts in brown bears (Ursus arctos), where torpor is only
      associated with shallow decreases in Tb. The results were compared across
      hibernator species for which immune and Tb data were available. METHODS AND
      RESULTS: The white blood cell counts were determined by flow cytometry in 13
      bears captured in the field both during summer and winter over 2 years time. Tb
      dropped from 39.6+/-0.8 to 33.5+/-1.1 degrees C during hibernation. Blood
      neutrophils and monocytes were lower during hibernation than during the active
      period (47%, p= 0.001; 43%, p=0.039, respectively), whereas no change in
      lymphocyte counts was detected (p=0.599). Further, combining our data and those
      from 10 studies on 9 hibernating species suggested that the decline in Tb
      explained the decrease in innate immune cells (R(2)=0.83, p<0.0001). CONCLUSIONS:
      Bears have fewer innate immune cells in circulation during hibernation, which may
      represent a suppressed innate immune system. Across species comparison suggests
      that, both in small and large hibernators, Tb is the main driver of immune
      function regulation during winter dormancy. The lack of a difference in
      lymphocyte counts in this context requires further investigations.

PMID- 23532626
TI  - DexaBEAM versus ICE salvage regimen prior to autologous transplantation for
      relapsed or refractory aggressive peripheral T cell lymphoma: a retrospective
      evaluation of parallel patient cohorts of one center.
AB  - High-dose chemotherapy (HDT) followed by autologous stem cell transplantation
      (ASCT) is considered standard in the treatment of patients with relapsed or
      refractory aggressive peripheral T cell lymphoma (PTCL). However, the optimal
      salvage regimen before ASCT has not yet been established. We retrospectively
      analyzed 31 patients with relapsed or refractory aggressive PTCL after
      anthracycline-based first-line chemotherapy who received either DexaBEAM
      (dexamethasone, carmustine, etoposide, cytarabine, and melphalan; n = 16) or ICE
      (ifosfamide, carboplatin, and etoposide; n = 15) regimen as first salvage
      chemotherapy followed by HDT/ASCT. The overall response rate (OR) was
      significantly higher for patients treated with DexaBEAM (69 %; 95 % confidence
      interval 46.0-91.5 %) as compared to the ICE group (20 %; 95 % confidence
      interval -0.2-40.2 %; P = 0.01), with higher complete response (CR; 38 %; 95 %
      confidence interval 13.8-61.2 %; vs. 7 %; 95 % confidence interval -6.0-19.6 %)
      as well as partial response (PR; 31 vs. 13 %) rate. Changing regimen due to
      failure of first salvage therapy, 12 patients initially receiving ICE still
      achieved an OR of 58 % (33 % CR, 25 % PR) with DexaBEAM as second salvage
      therapy, whereas in three patients receiving ICE after DexaBEAM failure, only one
      achieved an OR (1 PR). Median progression-free survival was significantly higher
      in the DexaBEAM group (6.4 vs. 2 months; P = 0.01). Major adverse event in both
      groups was myelosuppression with higher but tolerable treatment-related toxicity
      for patients in the DexaBEAM group. For all patients proceeding to HDT/ASCT, a 3
      year overall survival was 50 %. Together, considering the limitations of the
      retrospective design of the evaluation and the small sample size, our data
      suggest that DexaBEAM salvage chemotherapy is superior to ICE for patients with
      relapsed or refractory aggressive PTCL for remission induction prior to
      autologous transplantation, with higher but manageable treatment-related
      toxicity. 

PMID- 23532627
TI  - Validation of a food frequency questionnaire for retrospective estimation of diet
      during the first 2 years of life.
AB  - This study aims to validate a Food Frequency Questionnaire (FFQ), specifically
      designed to retrospectively estimate dietary intake and supplement consumption
      during the first 2 years of life in children from resource poor households in
      semi-rural Mexico. The FFQ querying about diet during the first 2 years of life
      was administered to mothers of children (N = 84), who participated in a
      prospective study 3-5 years earlier, in which complementary feeding practice
      questionnaires and 24-h recall (24hrR) were collected at several time points
      during the first 2 years of life to evaluate dietary and vitamin supplement
      intake. The resulting FFQ data were compared to intake data collected during the
      original study using Spearman correlations, deattenuated correlations and
      Wilcoxon signed-rank tests. Total energy intake, as estimated by the
      retrospective and original instruments, did not differ in the second year (Yr2);
      correlations between the measures were significant (r = 0.40, p < 0.001). The
      24hrR and FFQ-Yr2 were significantly correlated for dietary intake of vitamins
      B6, B12 (p < 0.001) and folate (p < 0.01); however, after including vitamin
      supplement intake, the two dietary instruments were correlated only for vitamins
      A and B12 (p < 0.05). The FFQ provides a reasonable estimate of a child's dietary
      intake of energy and key micronutrients during the second year of life, and
      permits accurate ranking of intake 3-5 years after birth. 

PMID- 23532628
TI  - Association of interleukin-10, tumor necrosis factor-alpha and transforming
      growth factor-beta gene polymorphisms with the outcome of diffuse large B-cell
      lymphomas.
AB  - BACKGROUND: Published data indicate that common genetic variants in
      immune/inflammatory response genes can affect the outcome of diffuse large B-cell
      lymphomas (DLBCL). This study investigated the association of interleukin (IL)-10
      (-3575, -1082), tumor necrosis factor (TNF)-alpha -308 and transforming growth
      factor (TGF)-beta Leu10Pro gene polymorphisms with clinical characteristics and
      outcome of DLBCL patients treated with rituximab-CHOP therapy. METHODS: Between
      January 2004 and December 2007, a total of 84 patients with newly diagnosed DLBCL
      entered into this study. Genotypes were determined with PCR-based methodology.
      RESULTS: Patients presenting with B symptoms had IL-10 -3575 TA/AA genotypes more
      frequently than TT genotype [odds ratio (OR) 2.89, 95 % confidence interval (CI)
      1.11-7.57; p = 0.03]. Carriers of TGF-beta Pro10 allele more frequently had an
      advanced clinical stage III/IV (OR 4.65, 95 % CI 1.33-16.19; p = 0.016) and
      intermediate-high/high IPI score (OR 5.37, 95 % CI 1.45-20.0; p = 0.012). In
      rituximab-CHOP-treated patients (n = 64), the TNF-alpha -308 AG/AA carriers had
      shorter overall (p = 0.048) and event-free survival (p = 0.07) compared to GG
      carriers. In multivariate analysis of prognostic factors for survival, the TNF
      alpha AG/AA genotypes were significantly associated with inferior survival of
      lymphoma patients (OR 0.23, 95 % CI 0.07-0.78; p = 0.018). CONCLUSION: Our
      results indicate the association of IL-10 -3575 and TGF-beta Leu10Pro gene
      variations with clinical characteristics. In patients treated with rituximab-CHOP
      therapy, the TNF-alpha -308 AG/AA genotypes showed a significantly less favorable
      survival than the GG genotype.

PMID- 23532629
TI  - Erythropoietin treatment in chemotherapy-induced anemia in previously untreated
      advanced esophagogastric cancer patients.
AB  - BACKGROUND: The impact of erythropoiesis-stimulating agents in chemotherapy
      induced anemia has been a constant topic of debate over recent years. We
      prospectively assessed the efficacy of epoetin beta (Epo-b) in improving
      hemoglobin (Hb) levels and outcome in patients within an open label, randomized
      clinical phase II trial with advanced or metastatic gastric/esophagogastric
      cancer. METHODS: Previously untreated patients were randomized to receive 3
      weekly cycles of capecitabine (1000 mg/m(2) bid) for 14 days plus on day 1 either
      irinotecan 250 mg/m(2) or cisplatin 80 mg/m(2). Epo-b (30000 IU once weekly) was
      initiated in patients with Hb <11 g/dl and continued until Hb >=12 g/dl was
      reached. If after 4 weeks the Hb increase was <0.5 g/dl, Epo-b was increased to
      30000 IU, twice weekly. RESULTS: Of 118 patients enrolled, 32 received Epo-b
      treatment; of these, 65 % achieved an increase in Hb levels of at least 2 g/dl,
      with 74 % achieving the target Hb of >=12 g/dl. Within the study population,
      patients receiving Epo-b showed better overall survival (median 14.5 vs. 8.0
      months, P = 0.056) as well as a significantly improved disease control rate (78
      vs. 55 %, P = 0.025). Patients in the irinotecan group profited significantly (P
      < 0.05) in terms of progression-free survival and overall survival under Epo-b
      treatment (median 6.5 vs 4.1 months and median 15.4 vs 8.4 months, respectively).
      CONCLUSIONS: Epo-b was effective in raising Hb levels in patients with advanced
      esophagogastric cancer. Patients receiving Epo-b had a significantly increased
      response to chemotherapy and a clear trend to improved survival.

PMID- 23532630
TI  - Repeat coronary revascularization after coronary artery bypass surgery in older
      adults: the Society of Thoracic Surgeons' national experience, 1991-2007.
AB  - BACKGROUND: A major advantage of coronary artery bypass graft surgery (CABG)
      relative to percutaneous coronary intervention is its durability, yet there is a
      paucity of information on rates and predictors of repeat coronary
      revascularization after CABG in the modern era. METHODS AND RESULTS: We included
      patients >=65 years from the Society of Thoracic Surgeons' National Adult Cardiac
      Surgery Database who were undergoing first-time isolated CABG from 1991 to 2007
      (n=723 134, median age 73 years). After linking to Medicare claims data, long
      term outcomes of CABG (up to 18 years after surgery) were examined by use of
      cumulative incidence curves. Multivariable Cox proportional hazard analysis was
      used to identify factors associated with 1- and 5-year repeat revascularization
      trends and variability. We found that the overall 18-year survival rate was 20%.
      Cumulative incidences of any repeat revascularization (percutaneous coronary
      intervention or CABG, yet most often percutaneous coronary intervention) were 2%,
      7%, 13%, and 16% at 1, 5, 10, and 18 years after surgery, respectively. The rates
      of repeat CABG procedures were quite low for all time points (0.1%, 0.6%, 1.3%,
      and 1.7%, respectively). Female sex, disease severity represented by a history of
      percutaneous coronary intervention, preoperative dialysis, and partial
      revascularization were strongly associated with a higher revascularization rate,
      whereas advanced age, left main disease, and smoking were associated with a lower
      rate. There was approximately a 2-fold variation in repeat revascularization
      rates across centers at 1 year (interquartile range 1.7-3.6%) and 5 years
      (interquartile range 6.7-12.0%). CONCLUSIONS: Repeat revascularization is
      performed infrequently among older patients who undergo CABG; however, these
      rates vary substantially by patient subgroups and among providers.

PMID- 23532631
TI  - Adults with autism--a new minority.

PMID- 23532632
TI  - Debunking 'race' and asserting social determinants as primary causes of cancer
      health disparities: outcomes of a science education activity for teens.
AB  - Cancer health disparities are often described as the unequal burden of cancer
      deaths in one racial/ethnic group compared to another. For example, national
      cancer statistics in the USA shows that Blacks die the most for 9 of the top 10
      cancers in men and women. When asked about the underlying causes for this
      disparity, teen participants speculated that it is primarily due to genetics or
      biology. This speculation appears to be based on a false concept of 'race.' A
      science activity was created to counter the false concept that genetics/biology
      underlie the categorization of humans into different 'races.' This activity
      provided teen participants with first-hand evidence of how they are all related
      at one genetic locus, and how they are more genetically related across
      racial/ethnic groups than within them. Results of surveys given before and after
      the activity show that they change their perceptions of 'race.' Before the
      activity, they view themselves as most related at the genetic level to 1-2 well
      known individuals (i.e., celebrities) who they perceive as members of their own
      'race' mainly because of similar appearance. After the activity, they view
      themselves as related to more/all the celebrities or they state that they do not
      know to whom they are most related. This increased awareness of the uncertainty
      between the apparent 'race' of an individual and their genetics drives teens to
      dismiss genetics or biology as the primary cause of racial/ethnic disparities in
      cancer outcomes. Instead, they consider the unequal distribution of the social
      determinants of health as the primary cause of cancer disparities.

PMID- 23532633
TI  - Implication of circulating omentin-1 level on the arterial stiffening in type 2
      diabetes mellitus.
AB  - Omentin-1 is an adipokine implicated in diabetes, inflammation, and
      cardiovascular disease. However, no prospective studies have examined the impact
      of circulating omentin-1 levels on arterial stiffening in patients with type 2
      diabetes mellitus. For the purpose of this study, we recruited 120 patients with
      type 2 diabetes mellitus and measured serum omentin-1, adiponectin, and high
      sensitivity C-reactive protein levels as well as other cardiovascular risk
      factors. Arterial stiffness was assessed by brachial ankle pulse wave velocity
      (baPWV). An increase in the level of circulating omentin-1 over a period of 1
      year was positively correlated with changes in levels of HbA1c and serum
      adiponectin as well as baPWV. Subjects with higher baseline serum omentin-1
      levels tended to have a reduced arterial stiffness after 1 year (P for linear
      trend = 0.03). In the group with increased baPWV after 1 year, the magnitude of
      increase of circulating omentin-1 levels was significantly higher than in the
      group with a lower baPWV after 1 year (134.3 [16.6, 277.1] ng/mL vs. 15.9 [-67.6,
      145.7] ng/mL, P < 0.01). Multiple stepwise logistic regression analysis revealed
      that an increase in systolic blood pressure and an increase in serum omentin-1
      level were independently correlated with arterial stiffening, even after
      adjusting for other cardiovascular risk factors and medication history. Baseline
      serum omentin-1 levels can predict arterial stiffness changes occurring within a
      year. Furthermore, changes in serum omentin-1 levels after a year can function as
      independent markers of arterial stiffening in patients with type 2 diabetes
      mellitus.

PMID- 23532634
TI  - Adrenocortical reserves in hyperthyroidism.
AB  - Explicit data regarding the changes in adrenocortical reserves during
      hyperthyroidism do not exist. We aimed to document the capability (response) of
      adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to
      euthyroidism, and to describe factors associated with these responses. A standard
      dose (0.25 mg/i.v.) ACTH stimulation test was performed to the same patients
      before hyperthyroidism treatment, and after attainment of euthyroidism. Baseline
      cortisol (Cor(0)), DHEA-S (DHEA-S(0)), cortisol binding globulin (CBG), ACTH,
      calculated free cortisol (by Coolen's equation = CFC), free cortisol index (FCI),
      60-min cortisol (Cor(60)), and DHEA-S (DHEA-S(60)), delta cortisol (DeltaCor),
      delta DHEA-S (DeltaDHEA-S) responses were evaluated. Forty-one patients [22
      females, 49.5 +/- 15.2 years old, 32 Graves disease, nine toxic nodular goiter]
      had similar Cor(0), DHEA-S(0), CFC, FCI, and DHEA-S(60) in hyperthyroid and
      euthyroid states. Cor(60), DeltaCor, and DeltaDHEA-S were lower in
      hyperthyroidism. In four (10 %) patients the peak ACTH-stimulated cortisol values
      were lower than 18 MUg/dL. When the test repeated after attainment of
      euthyroidism, all of the patients had normal cortisol response. Regression
      analysis demonstrated an independent association of Cor(60) with free T3 in
      hyperthyroidism. However, the predictors of CFC, FCI, and DHEA-S levels were
      serum creatinine levels in hyperthyroidism, and both creatinine and transaminase
      levels in euthyroidism. ACTH-stimulated peak cortisol, delta cortisol, and delta
      DHEA-S levels are decreased during hyperthyroidism, probably due to increased
      turnover. Since about 10 % of the subjects with hyperthyroidism are at risk for
      adrenal insufficiency, clinicians dealing with Graves' disease should be alert to
      the possibility of adrenal insufficiency during hyperthyroid stage.

PMID- 23532635
TI  - Low appendicular skeletal muscle mass (ASM) with limited mobility and poor health
      outcomes in middle-aged African Americans.
AB  - BACKGROUND: Recent efforts to provide a consensus definition propose that
      sarcopenia be considered a clinical syndrome associated with the loss of both
      skeletal muscle mass and muscle function that occurs with aging. Validation of
      sarcopenia definitions that include both low muscle mass and poor muscle function
      is needed. METHODS: In the population-based African American Health (AAH) study
      (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a
      clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4
      (2004). Muscle mass was measured using dual energy x-ray absorptiometry and
      mobility by a 6-min walk test and 4-m gait walk test. Height corrected
      appendicular skeletal mass (ASM; 9.0 +/- 1.5 in n = 124 males, 8.3 +/- 2.2 in n =
      195 females) was computed as total lean muscle mass in arms and legs (kilograms)
      divided by the square of height (meters). Cross-sectional and longitudinal (6
      year) associations of low ASM (bottom 25 % AAH sample; <7.96 males and <7.06
      females) and low ASM with limited mobility (4-m gait walk <=1 m/s or 6-min walk
      <400 m) were examined for basic activities of daily living (ADL) difficulties,
      instrumental activities of daily living (IADL) difficulties, frailty, falls, and
      mortality (longitudinal only). RESULTS: Low ASM with limited mobility was
      associated with IADL difficulties (p = .008) and frailty (p = .040) but not with
      ADL difficulties or falls in cross-sectional analyses; and with ADL difficulties
      (p = .022), IADL difficulties (p = .006), frailty (p = .039), and mortality (p =
      .003) but not with falls in longitudinal analyses adjusted for age and gender.
      Low ASM alone was marginally associated with mortality (p = .085) but not with
      other outcomes in cross-sectional or longitudinal analyses. CONCLUSION: Low ASM
      with limited mobility is associated with poor health outcomes among late middle
      aged African Americans.

PMID- 23532636
TI  - Surfactant-free CuInS2 nanocrystals: an alternative counter-electrode material
      for dye-sensitized solar cells.
AB  - Surfactant-free CuInS2 (CIS) nanocrystals (NCs) were synthesized by replacing
      organic capping ligands with inorganic ions S(2-). The efficacy of ligand
      exchange was probed by thermogravimetric analysis (TGA), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction
      (XRD), UV-vis spectroscopy, and Fourier-transform infrared (FTIR). The surfactant
      free CIS NCs films were obtained by drop-casting onto the clean FTO glass. The
      electrical conductivity and electrocatalytic activity of CIS NCs films were
      sharply increased due to the improved interparticle coupling after ligand
      exchange. When the surfactant-free CIS films were used as counter electrode (CE)
      in dye-sensitized solar cells (DSSCs), a conversion efficiency of eta = 5.77% was
      achieved without sintering.

PMID- 23532637
TI  - B and T lymphocyte attenuator is highly expressed on intrahepatic T cells during
      chronic HBV infection and regulates their function.
AB  - BACKGROUND: T cell antiviral function is impaired during chronic hepatitis B
      (CHB). Programmed death-1 (PD-1) impairs antiviral T cell responses, but
      dysfunction is not always reversed by blockade of PD-1 pathway. Whether distinct
      T cell populations expressing different sets of inhibitory molecules exist has
      not been determined. METHODS: We studied the expression of the B and T lymphocyte
      attenuator (BTLA) on both peripheral blood mononuclear cells (PBMC) and
      intrahepatic lymphocytes, and the effects of blocking BTLA on circulating and
      intrahepatic T cells in CHB patients. Sixty-three CHB patients who underwent
      liver biopsy were enrolled. The expression of BTLA and PD-1 on PBMC and
      intrahepatic T cells was assessed by flow cytometry with antibodies to T cell
      differentiation molecules. Functional recovery was evaluated by analyzing
      production of interferon (IFN)-gamma and interleukin (IL)-2 after incubation of T
      cells with anti-CD3 and irradiated mature dendritic cells in the presence of anti
      BTLA, anti-PD-1, or both. RESULTS: Intrahepatic T cells expressed higher levels
      of BTLA than their peripheral counterparts. A significant fraction of
      intrahepatic T cells coexpressed BTLA and PD-1 and showed deep exhaustion of T
      cell responses. Blockade of the BTLA pathway enhanced both intrahepatic and PBMC
      T cell proliferation and cytokine secretion, and exhibited an additive effect
      upon blockage of PD-1. CONCLUSIONS: Upregulation of inhibitory receptor BTLA
      restricts T cell responses in CHB. T cell exhaustion by high antigen
      concentrations exacerbates dysfunction of peripheral and intrahepatic T cells.
      Blockage of BTLA is a potential therapeutic approach for chronic HBV infection
      that may act by restoring antiviral T cell responses.

PMID- 23532642
TI  - Politics: Be part of it.

PMID- 23532638
TI  - Positive glypican-3 expression in early hepatocellular carcinoma predicts
      recurrence after hepatectomy.
AB  - BACKGROUND: Glypican-3 (GPC3) is a new prognostic factor after curative
      hepatectomy in patients with hepatocellular carcinoma (HCC), and the expression
      of GPC3 is known to be associated with postoperative metastasis. However, the
      role of GPC3 in patients with early HCC remains unknown. METHODS: We
      retrospectively studied 55 patients with early HCC (total 99 nodules) who
      underwent initial hepatectomy between 1995 and 2010. Clinicopathological features
      and surgical outcomes were compared in relation to GPC3 expression. RESULTS: The
      GPC3-positive expression was seen in 28 of 55 patients (50.9 %) with early HCC
      (44 of 99 nodules). The GPC3-positive expression was significantly associated
      with hepatitis C virus (HCV) infection (P = 0.0019) and with multiple early HCCs
      (P < 0.0001). The 5-year disease-free survival rate was significantly lower in
      patients with GPC3-positive early HCC (27 %) than in patients with GPC3-negative
      early HCC (62 %, P = 0.0036). The GPC3 expression was a significant independent
      prognostic factor for disease-free survival. However, it showed no significant
      difference in overall survival. CONCLUSIONS: The GPC3 expression is capable to be
      a new prognostic factor for disease-free survival in patients with early HCC.

PMID- 23532643
TI  - Retention cyst in chronic otitis media.

PMID- 23532644
TI  - Ludwig angina progressing to fatal necrotizing fasciitis.

PMID- 23532645
TI  - Mucocele: Retention and extravasation types.

PMID- 23532646
TI  - Local anesthesia for nasal and sinus surgery.

PMID- 23532647
TI  - Behcet disease as a cause of hearing loss: A prospective, placebo-controlled
      study of 29 patients.
AB  - We conducted a prospective, placebo-controlled study to determine the incidence
      and severity of inner ear involvement and hearing loss in patients with Behcet
      disease. Our study population was made up of 29 patients with Behcet disease and
      28 healthy controls. Audiometric pure-tone thresholds and transient evoked
      otoacoustic emission (TEOAE) levels were determined in both groups. The main
      outcome measures were pure-tone audiometry (PTA) levels and TEOAE levels in the
      two groups. PTA detected a sensorineural hearing loss in 10 of the 29 patients
      (34.5%). The difference in audiometric findings between the two groups was
      statistically significant at 1, 2, 4, and 8 kHz (p <= 0.0498). A comparison of
      TEOAE levels revealed that the difference in sound-to-noise ratio between the two
      groups was not significant at 1, 1.5, 2, and 3 kHz, but it was significant in 4
      kHz (p = 0.02), and the difference in reproducibility between the two groups was
      significant at 2 and 4 kHz (p <= 0.03). We conclude that all patients with Behcet
      disease should be screened for hearing impairment and subsequently treated if an
      impairment is discovered.

PMID- 23532648
TI  - Middle ear metastasis from dormant breast cancer as the initial sign of
      disseminated disease 20 years after quadrantectomy.
AB  - We describe an unusual case of breast cancer metastatic to the middle ear in a 71
      year-old woman. The metastasis was the initial sign of disseminated disease 20
      years after the patient had undergone a quadrantectomy for her primary disease.
      Computed tomography (CT) demonstrated the presence of an intratympanic mass with
      a soft-tissue density that was suggestive of chronic inflammation. The patient
      underwent a canal-wall-down tympanoplasty. When a brownish mass was found around
      the ossicles, a mastoidectomy with posterior tympanotomy was carried out.
      However, exposure of the tumor was insufficient, and therefore the posterior wall
      of the ear canal had to be removed en bloc. Some tumor was left on the round
      window membrane so that we would not leave the patient with a total hearing loss.
      Our case highlights the limitations of CT and magnetic resonance imaging in
      differentiating inflammatory and neoplastic lesions.

PMID- 23532649
TI  - Does tonsillectomy affect the outcome of drug treatment for the eradication of
      gastric H pylori infection? A pilot study.
AB  - Eradication of Helicobacter pylori, which is associated with diverse
      gastroduodenal pathologies of varying severity, is sometimes challenging. We
      conducted a prospective study to determine the effect of tonsillectomy on the
      eradication of H pylori from the gastrointestinal tract. Our study population was
      made up of 46 patients-32 females and 14 males, aged 14 to 58 years (mean: 28.84
      +/- 9.65)-who had chronic tonsillitis and concomitant dyspepsia. An initial
      gastrointestinal endoscopy was performed to obtain specimens for histology and a
      rapid urease test. These gastroscopies revealed that 32 patients were H pylori
      positive (69.6%) and 14 were H pylori-negative (30.4%); these groups were
      designated A and B, respectively. The 32 H pylori-positive patients were divided
      into three subgroups based on the sequence in which they underwent drug therapy
      and tonsillectomy. All 3 subgroups received the same 14-day combination-drug
      regimen for eradication of gastric H pylori. The patients in group A1 (n = 12)
      underwent tonsillectomy prior to receiving drug treatment; 2 months after the
      cessation of drug therapy, they underwent a second gastroscopy. The patients in
      group A2 (n = 10) received drug treatment first followed by tonsillectomy; 2
      months later, they underwent their second gastroscopy. The patients in group A3
      (n = 10) received drug treatment first, then they underwent a second gastroscopy,
      and then they were taken for tonsillectomy. The success or failure of H pylori
      eradication was determined by the second gastroscopy. Also, analyses were
      performed after tonsillectomy to look for H pylori infection in tonsillar
      specimens. Eradication of gastric H pylori was achieved in 9 of the 12 group A1
      patients (75.0%), 8 of the 10 group A2 patients (80.0%), and 7 of the 10 group A3
      patients (70.0%); there were no statistically significant differences among the
      three groups. Likewise, there were no significant differences between any
      subgroups or combination of subgroups in terms of tonsillar positivity. As far as
      we know, this is the first study to investigate the effect of tonsillectomy on
      the outcome of H pylori eradication treatment. In light of our findings, we may
      speculate that tonsillar tissue does not seem to be a reservoir for H pylori
      infection. Although tonsillectomy had no significant effect on gastric H pylori
      eradication in our study, our results might have been skewed by the relatively
      small size of our sample.

PMID- 23532650
TI  - A prospective study of parents' compliance with their child's prescribed
      analgesia following tonsillectomy.
AB  - We conducted a prospective study to assess how well parents ensured that their
      children received their prescribed analgesia following tonsillectomy. Our study
      was based on 69 cases of tonsillectomy that were carried out at our tertiary
      pediatric care center. Postoperatively, all patients were prescribed paracetamol
      (acetaminophen) on the basis of their weight; the standard pediatric dosage of
      this agent at the time of our study was 60 mg/kg/day. The parents were telephoned
      2 weeks postoperatively to assess their compliance with this regimen. Of the
      original 69 patients who had been recruited, 66 completed the study-35 girls and
      31 boys, aged 2 to 15 years (mean: 7.0; median 5.5). According to the parents,
      only 15 children (22.7%) received our recommended 60-mg/kg/day dosage and were
      thus determined to be fully compliant. Overall, parents reported a wide variation
      in the amount of drug administered, ranging from 12.5 to 111.0 mg/kg/day (mean:
      44.8), indicating that parents often underdose their children. We recommend that
      more emphasis be placed on weight-directed, parent-provided analgesia during the
      post-tonsillectomy period.

PMID- 23532651
TI  - Craniofacial and shoulder asymmetry and its relationship to temporomandibular
      disorder: A study of 183 patients.
AB  - We conducted a prospective study to ascertain the prevalence of features of
      craniofacial and shoulder asymmetry and to determine if they are related to
      temporomandibular disorder (TMD). Our study population was made up of 183
      patients-105 females and 78 males, aged 8 to 92 years (mean: 53.5; median: 60)
      who presented to a private otolaryngologic practice in a rural retirement
      community in Arizona. These patients completed a questionnaire to determine their
      self-assessment of the their body asymmetry. Next, all patients underwent a nurse
      evaluation for the presence or absence of asymmetry, which was based on the
      relative position of the ears, lateral canthi, hemimandibles, and shoulders. All
      patients were then evaluated independently by a physician for the presence or
      absence of TMD. The most important finding of this study was that asymmetry as
      determined by the nurse evaluation was associated with a relative risk of TMD of
      5.89 (p = 0.0001); the perception of asymmetry on the patient self-assessments
      was associated with a relative risk of only 1.86 (p = 0.0026). We conclude that
      the recognition and diagnosis of TMD is significantly enhanced by a brief
      evaluation by a health professional who has been trained in recognizing the signs
      of facial and shoulder asymmetry.

PMID- 23532652
TI  - Necrotizing cervical fasciitis: Prognosis based on a new grading system.
AB  - We conducted a 10-year retrospective study to determine the prognosis of
      necrotizing cervical fasciitis (NCF). Our study population included 38 patients
      32 males and 6 females, aged 10 months to 70 years (mean: 55 yr)-who had
      presented for management of NCF at our tertiary care hospital between Jan. 1,
      2000, and Dec. 31, 2009. We classified each case into four categories based on
      the duration of disease prior to presentation, the severity of disease, and other
      factors that influence outcomes. We found that the most important factor in
      determining prognosis was the time interval between the onset of NCF and
      subsequent presentation for specialist or surgical intervention. Patients with a
      higher grade of NCF had longer hospital stays. Although aggressive surgical and
      medical intervention is the gold standard for the management of NCF, many of our
      patients presented with a relatively healthy appearing wound, which could mislead
      the evaluating clinician and delay prompt management. We believe that our new
      grading system will help obviate this problem and make clinicians more vigilant
      when faced with a new case of necrotizing fasciitis.

PMID- 23532653
TI  - Hypopharyngeal lipoma causing obstructive sleep apnea: Discovery on dental cone
      beam CT.
AB  - Cone-beam computed tomography (CBCT) is primarily used for a variety of dental
      purposes, but it may also yield nondental findings that can have significant
      implications for patient health. For example, physicians should be aware that
      CBCT can identify some of the etiopathogenic causes of obstructive sleep apnea,
      as occurred in the case described in this report. The patient was a 76-year-old
      man who presented to a dentist for implant therapy. A CBCT that had been
      performed in preparation for dental implant placement revealed the presence of a
      large hypopharyngeal lesion that was obstructing the airway. An otolaryngologist
      excised the lesion, which on biopsy proved to be a lipoma. Following removal of
      the lesion, the patient's episodic sleep apnea and snoring resolved. Medical
      physicians should be aware of maxillofacial CBCT technology and its ability to
      identify lesions that could cause potential life-threatening situations.

PMID- 23532654
TI  - Intranasal tooth and associated rhinolith in a patient with cleft lip and palate.
AB  - We report the case of a 9-year-old girl who presented with a complaint of a
      malodorous bloody discharge from the left naris. The patient had previously
      undergone a complete repair of left-sided cleft lip and palate. Clinical
      examination revealed hyperplasia of the nasal mucosa on the left side. X-ray
      examination of the nasal cavity demonstrated a radiopaque structure that
      resembled a tooth and a radiopaque mass similar to an odontoma that was adherent
      to the root of the suspected tooth. With the patient under general anesthesia,
      the structure was removed. On gross inspection, the structure was identified as a
      tooth with a rhinolith attached to the surface of its root. Microscopic
      examination revealed normal dentin and pulp tissue. A nonspecific inflammatory
      infiltrate was observed around the rhinolith, and areas of regular and irregular
      mineralization were seen. Some mineralized areas exhibited melanin-like brownish
      pigmentation. Areas of mucus with deposits of mineral salts were also observed.
      Rare cases of an intranasal tooth associated with a rhinolith have been described
      in the literature. We believe that this case represents only the second published
      report of an intranasal tooth associated with a rhinolith in a patient with cleft
      lip and palate.

PMID- 23532655
TI  - Internal carotid artery in zone IIb and its implications: A case report.
AB  - The potential for aberrant anatomy in the neck should be respected in order to
      avoid unexpected and potentially devastating injury during surgical and other
      procedures. Anatomic variations involving the internal carotid artery are
      believed to exist in as much as 6% of the population. We describe a case of a
      tortuous internal carotid artery that was found in zone IIb during a neck
      dissection in a 60-year-old man, and we discuss the implications of this anomaly.

PMID- 23532656
TI  - Oncocytoma of the nasal cavity: A case report.
AB  - Oncocytomas arising in the nasal cavity are quite rare. These entities more
      commonly occur in the major salivary glands, minor salivary glands, respiratory
      seromucinous glands, and endocrine organs. Very few cases of oncocytoma in the
      nasal cavity have been reported, with only 5 diagnosed as malignant. This article
      describes a case involving an 81-year-old man with a nasal oncocytoma that was
      completely resected with an endoscopic medial maxillectomy. The diagnostic
      rationale is discussed, along with a review of the literature.

PMID- 23532657
TI  - Cerebrospinal fluid leak of the fallopian canal.
AB  - Spontaneous cerebrospinal fluid (CSF) leaks from the fallopian canal are
      extremely rare, as only a few cases have been reported in the world literature.
      We describe a case of spontaneous CSF otorrhea through an enlarged geniculate
      fallopian canal. The patient was a 45-year-old woman who presented with a history
      of CSF rhinorrhea and otorrhea from the right ear. Myringotomy and tube insertion
      revealed CSF otorrhea. Contrast-enhanced computed tomography revealed that the
      geniculate fossa was smoothly enlarged (demonstrating remodeling of bone). A
      middle fossa craniotomy with temporal bone exploration was performed.
      Intraoperative inspection detected the presence of a fistula secondary to a
      lateral extension of the subarachnoid space through the labyrinthine segments of
      the fallopian canal. We discuss the management of this unusual finding, which
      involves sealing the fistula while preserving facial nerve function.

PMID- 23532658
TI  - Anterior jugular phlebectasia and tinnitus: A case report.
AB  - Abnormal dilation of a normal anterior jugular vein is a rare anomaly and usually
      presents as a neck lump. To the best of our knowledge, this is the first report
      in the literature of such a case in which the patient presented with severe
      tinnitus. Excision of the dilated portion of the anterior jugular vein in our
      patient alleviated the severe tinnitus.

PMID- 23532659
TI  - Bilateral Gore-Tex implant extrusion following type I thyroplasty.

PMID- 23532660
TI  - Metastatic hepatocellular carcinoma in the nasal vestibule.

PMID- 23532661
TI  - Case report: Metastatic breast cancer presenting as a hypopharyngeal mass.
AB  - Although carcinoma of the breast has a propensity toward distant metastasis,
      metastasis to the head and neck is uncommon. Most patients with metastasis to the
      head and neck region present with cervical lymphadenopathy; however, spread to
      the upper aerodigestive tract has been described previously. We present a case of
      a patient found to have a pedunculated mass in her right piriform sinus. When she
      swallowed, the mass would completely prolapse into the esophagus and cause
      symptoms. Subsequent workup revealed widespread metastatic disease, for which the
      patient was treated with chemoradiotherapy. Microlaryngoscopy with excision of
      the mass was performed for palliation of her dysphagia, and a diagnosis of
      metastatic breast carcinoma was obtained. The patient healed well from the
      excision and went on to be treated for the metastatic breast cancer. To our
      knowledge, our report represents the first case of metastatic breast carcinoma
      presenting as severe dysphagia.

PMID- 23532662
TI  - Mastoid osteoma: A case report and review of the literature.
AB  - We describe the case of a 22-year-old woman who presented with a slowly growing
      osseous lesion of the mastoid cortex. On computed tomography, the lesion was
      found to involve the mastoid cortex, with which it demonstrated similar
      attenuation. The indications for treatment in this case were the patient's
      sensation of a mass effect, the encroachment of the mass onto the external
      auditory meatus, and a cosmetic deformity. The tumor was removed in its entirety
      via a postauricular approach. Findings on histopathologic examination were
      consistent with a compact osteoma. Mastoid osteomas are rare, benign tumors. If
      their growth significantly occludes the meatus, they may cause cosmetic
      deformities, conductive hearing loss, and recurrent external ear infections.
      Several other osseous lesions of the temporal bone should be considered in the
      differential diagnosis. The etiology of mastoid osteomas is poorly understood.
      Surgical management can be undertaken with minimal postoperative morbidity.

PMID- 23532663
TI  - Facile synthesis of nitrogen-doped graphene-ultrathin MnO2 sheet composites and
      their electrochemical performances.
AB  - Nitrogen-doped graphene-ultrathin MnO2 sheet composites (NGMCs) were prepared
      through a one-step hydrothermal method at low temperature (120  degrees C).
      Ultrathin MnO2 sheets were well-dispersed and tightly anchored on graphene
      sheets, which were doped with nitrogen simultaneously. NGMCs electrode exhibited
      enhanced capacitive performances relative to those of undoped graphene-ultrathin
      MnO2 sheets composites (GMCs). As the current density increased from 0.2 to 2
      A/g, the capacitance of NGMCs still retained ~74.9%, which was considerablely
      higher than that of GMCs (27%). Moreover, over 94.2% of the original capacitance
      was maintained after 2000 cycles, indicating a good cycle stability of NGMCs
      electrode materials.

PMID- 23532664
TI  - Age-related alterations in T-lymphocytes modulate key pathways in prostate
      tumorigenesis.
AB  - BACKGROUND: The primary risk for prostate cancer is aging, often associated with
      inflammation. Evidence implicates progressive age-related immune dysfunction with
      increased prostate cancer incidence and mortality. The aged T-cell response is
      characterized by increased production of pro-inflammatory cytokines, which could
      significantly contribute to prostate tumorigenesis through induction of key
      inflammation-mediated pro-survival factors. METHODS: T-cell function of the young
      (<6 month-old) glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock-out mouse
      mimics many of the hallmarks observed in an aged (>22-month-old) mouse. Serum and
      splenic T-lymphocytes from young GPAT-1(-/-) (6 months) and aged wild type (22
      months) mice were collected for in vitro studies, including a cytokine
      immunoarray for serum cytokine levels, luciferase assays for NF-kappaB activation
      and Western blot analyses for protein expression. RESULTS: The T-cell cytokine
      profile of the GPAT-1(-/-) mice mirrored that observed in aged wild type mice,
      including higher expression levels of IL-17. Serum- and T-cell-derived factors
      induced NF-kappaB activity in normal, non-transformed and prostate cancer
      epithelial cells, correlating with re-localization of NF-kappaB and increased
      protein expression of downstream targets of NF-kappaB. CONCLUSION: The aging and
      aging-mimic mice produced circulating factors that induce pro-inflammatory
      pathways in prostate cells, most notably NF-kappaB. These findings provide
      evidence that an aged T-cell may directly contribute to the increased risk for
      prostate cancer in the elderly and establish that the GPAT-1(-/-) model, which
      mimics many of the characteristics of an aged immune system, is a viable tool for
      investigating this novel area of cancer risk.

PMID- 23532665
TI  - Combination of high-dose dexamethasone and antiretroviral therapy rapidly
      improved and induced long-term remission of HIV-related thrombocytopenic purpura.
AB  - We present a case of HIV-related thrombocytopenic purpura (HIV-ITP) successfully
      treated with high-dose dexamethasone and antiretroviral therapy (ART). Although
      high-dose dexamethasone is regarded as the first-line therapy in adult patients
      with non-HIV ITP, there is limited information on treatment of HIV-ITP and long
      term prednisone therapy is considered the standard therapy. High-dose
      dexamethasone is preferable to conventional long-term prednisone therapy, because
      of fewer side effects mainly due to shorter steroid use. The ART helps achieve
      long-term remission for HIV-ITP, although this therapy lacks an immediate effect.
      In our patient, administration of high-dose dexamethasone resulted in rapid rise
      in platelet count and ART maintained long-term remission of HIV-ITP. The
      combination therapy is potentially suitable strategy for the treatment of
      patients with HIV-ITP and severe thrombocytopenia or bleeding. 

PMID- 23532666
TI  - Subchromosomal karyotype evolution in Equidae.
AB  - Equidae is a small family which comprises horses, African and Asiatic asses, and
      zebras. Despite equids having diverged quite recently, their karyotypes underwent
      rapid evolution which resulted in extensive differences among chromosome
      complements in respective species. Comparative mapping using whole-chromosome
      painting probes delineated genome-wide chromosome homologies among extant equids,
      enabling us to trace chromosome rearrangements that occurred during evolution. In
      the present study, we performed subchromosomal comparative mapping among seven
      Equidae species, representing the whole family. Region-specific painting and
      bacterial artificial chromosome probes were used to determine the orientation of
      evolutionarily conserved segments with respect to centromere positions. This
      allowed assessment of the configuration of all fusions occurring during the
      evolution of Equidae, as well as revealing discrepancies in centromere location
      caused by centromere repositioning or inversions. Our results indicate that the
      prevailing type of fusion in Equidae is centric fusion. Tandem fusions of the
      type telomere-telomere occur almost exclusively in the karyotype of Hartmann's
      zebra and are characteristic of this species' evolution. We revealed inversions
      in segments homologous to horse chromosomes 3p/10p and 13 in zebras and confirmed
      inversions in segments 4/31 in African ass, 7 in horse and 8p/20 in zebras.
      Furthermore, our mapping results suggested that centromere repositioning events
      occurred in segments homologous to horse chromosomes 7, 8q, 10p and 19 in the
      African ass and an element homologous to horse chromosome 16 in Asiatic asses.
      Centromere repositioning in chromosome 1 resulted in three different chromosome
      types occurring in extant species. Heterozygosity of the centromere position of
      this chromosome was observed in the kiang. Other subtle changes in centromere
      position were described in several evolutionary conserved chromosomal segments,
      suggesting that tiny centromere repositioning or pericentric inversions are quite
      frequent in zebras and asses.

PMID- 23532667
TI  - Expression of SLC22A1 variants may affect the response of hepatocellular
      carcinoma and cholangiocarcinoma to sorafenib.
AB  - Reduced drug uptake is an important mechanism of chemoresistance. Down-regulation
      of SLC22A1 encoding the organic cation transporter-1 (OCT1) may affect the
      response of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CGC) to
      sorafenib, a cationic drug. Here we investigated whether SLC22A1 variants may
      contribute to sorafenib chemoresistance. Complete sequencing and selective
      variant identification were carried out to detect single nucleotide polymorphisms
      (SNPs) in SLC22A1 complementary DNA (cDNA). In HCC and CGC biopsies, in addition
      to previously described variants, two novel alternative spliced variants and
      three SNPs were identified. To study their functional consequences, these
      variants were mimicked by directed mutagenesis and expressed in HCC (Alexander
      and SK-Hep-1) and CGC (TFK1) cells. The two novel described variants, R61S fs*10
      and C88A fs*16, encoded truncated proteins unable to reach the plasma membrane.
      Both variants abolished OCT1-mediated uptake of tetraethylammonium, a typical
      OCT1 substrate, and were not able to induce sorafenib sensitivity. In cells
      expressing functional OCT1 variants, OCT1 inhibition with quinine prevented
      sorafenib-induced toxicity. Expression of OCT1 variants in Xenopus laevis oocytes
      and determination of quinine-sensitive sorafenib uptake by high-performance
      liquid chromatography-dual mass spectrometry confirmed that OCT1 is able to
      transport sorafenib and that R61S fs*10 and C88A fs*16 abolish this ability.
      Screening of these SNPs in 23 HCC and 15 CGC biopsies revealed that R61S fs*10
      was present in both HCC (17%) and CGC (13%), whereas C88A fs*16 was only found in
      HCC (17%). Considering all SLC22A1 variants, at least one inactivating SNP was
      found in 48% HCC and 40% CGC. CONCLUSION: Development of HCC and CGC is
      accompanied by the appearance of aberrant OCT1 variants that, together with
      decreased OCT1 expression, may dramatically affect the ability of sorafenib to
      reach active intracellular concentrations in these tumors.

PMID- 23532668
TI  - Deviated nose correction: different outcomes according to the deviation type.
AB  - OBJECTIVES/HYPOTHESIS: The present study analyzed 631 deviated nose cases to
      determine the overall success rate of correction, the treatment outcomes
      according to the different types of deviation, and the revision rate. STUDY
      DESIGN: Case series study. METHODS: We reviewed 631 patients who underwent
      rhinoplasty for correction of a deviated nose with a minimum follow-up of 18
      months. Surgical outcomes were classified as excellent, good, fair, or no change.
      Deviations were classified into five types: type I, a straight tilted bony
      pyramid with straight tilted cartilaginous vault in the opposite direction; type
      II, a straight tilted bony pyramid with concavely or convexly bent cartilaginous
      vault; type III, a straight bony pyramid with tilted cartilaginous vault; type
      IV, a straight bony pyramid with bent cartilaginous vault, and type V, a straight
      tilted bony pyramid and tilted cartilaginous dorsum in the same direction.
      RESULTS: Postoperative assessment showed that 80.2% of the 631 patients had
      successful (excellent or good) outcomes, and 19.8% had unsuccessful (fair or no
      change) outcomes. Deformities of types I through V occurred in 169 (26.8%), 139
      (22.0%), 150 (23.8%), 101 (16.0%), and 72 (11.4%) patients, respectively, of whom
      34 (20.1%), 39 (28.1%), 11 (7.3%), 11 (10.9%), and 30 (41.7%) had unsuccessful
      outcomes. Analysis showed that the frequency of unsuccessful outcomes differed
      according to the deviation type (P < .001). Forty-one patients (6.5%) required
      revision rhinoplasty owing to dissatisfaction. CONCLUSIONS: An unsatisfactory
      surgical outcome is a significant risk following surgical correction of a
      deviated nose. The type of deviation affects the likelihood of a successful
      outcome. LEVEL OF EVIDENCE: 4.

PMID- 23532669
TI  - Geographically multifarious phenotypic divergence during speciation.
AB  - Speciation is an important evolutionary process that occurs when barriers to gene
      flow evolve between previously panmictic populations. Although individual
      barriers to gene flow have been studied extensively, we know relatively little
      regarding the number of barriers that isolate species or whether these barriers
      are polymorphic within species. Herein, we use a series of field and lab
      experiments to quantify phenotypic divergence and identify possible barriers to
      gene flow between the butterfly species Lycaeides idas and Lycaeides melissa. We
      found evidence that L. idas and L. melissa have diverged along multiple
      phenotypic axes. Specifically, we identified major phenotypic differences in
      female oviposition preference and diapause initiation, and more moderate
      divergence in mate preference. Multiple phenotypic differences might operate as
      barriers to gene flow, as shown by correlations between genetic distance and
      phenotypic divergence and patterns of phenotypic variation in admixed Lycaeides
      populations. Although some of these traits differed primarily between species
      (e.g., diapause initiation), several traits also varied among conspecific
      populations (e.g., male mate preference and oviposition preference).

PMID- 23532671
TI  - Preclinical evaluations of acellular biological conduits for peripheral nerve
      regeneration.
AB  - Various types of natural biological conduits have been investigated as
      alternatives to the current surgical standard approach for peripheral nerve
      injuries. Autologous nerve graft, the current gold standard for peripheral nerve
      damage, is limited by clinical challenges such as donor-site morbidity and
      limited availability. The purpose of this study was to evaluate the efficacy of
      using acellular xenographic conduits (nerve, artery, and dermis) for the repair
      of a 1.2 cm critical size defect of peripheral nerve in a rodent model. Four
      months post surgery, the animal group receiving acellular artery as a nerve
      conduit showed excellent physiological outcome in terms of the prevention of
      muscle atrophy and foot ulcer. Histological assessment of the bridged site
      revealed excellent axon regeneration, as opposed to the nonrepaired control group
      or the group receiving dermal conduit. Finally, the study evaluated the potential
      improvement via the addition of undifferentiated mesenchymal stem cells into the
      artery conduit during the bridging procedure. The mesenchymal stem cell-dosed
      artery conduit group resulted in significantly higher concentration of
      regenerated axons over artery conduit alone, and exhibited accelerated muscle
      atrophy rescue. Our results demonstrated that xenographic artery conduits
      promoted excellent axonal regeneration with highly promising clinical relevance.

PMID- 23532670
TI  - Potential regulatory role of in vitro-expanded Vdelta1 T cells from human
      peripheral blood.
AB  - gammadelta T cells represent a relevant proportion of T lymphocytes that express
      T cell receptors (TCRs) encoded by the gamma and delta T cell receptor genes.
      Whereas the most circulating gammadelta T cell type, Vdelta2 T cells, has been
      described and studied intensively, the potential role of Vdelta1 T cells remains
      largely unclear. Here, we identified that expanded peripheral blood Vdelta1 T
      cells stimulated with anti-human TCR Vdelta1 monoclonal antibody (mAb) in vitro
      predominantly expressed forkhead box p3 (Foxp3). In addition, these cells also
      expressed other regulatory T cell-related molecules, such as CD25, glucocorticoid
      induced TNFR family-related protein and cytotoxic T lymphocyte-associated protein
      4 (CTLA-4), and held the potent capacity for the production of transforming
      growth factor beta 1 (TGF-beta1). These autocrine and/or paracrine TGF-beta1
      could bind TGF-beta1 receptors on Vdelta1 T cells and induce sustained Foxp3
      expression. Moreover, Foxp3 expression coincided with high CD25 expression.
      CD25(high) Vdelta1 T cells exhibited stronger suppression on CD4(+) T cell
      proliferation compared with TGF-beta1-induced CD25(high) CD4(+) regulatory T
      cells. Therefore, our phenotypic and functional analyses first demonstrate the
      potential regulatory property of anti-human TCR Vdelta1 mAb-activated Vdelta1 T
      cells. These results will broaden our understanding about the role of peripheral
      blood Vdelta1 T cells under physical and pathological conditions.

PMID- 23532672
TI  - Pumpkin therapy.

PMID- 23532673
TI  - Mid term results of LCS knee: The Indian experience.
AB  - BACKGROUND: The low contact stress rotating platform (LCS RP) knee (DePuy
      Orthopedics, Inc, Warsaw, Indiana), in use for last four decades in Western
      population, is reported to have a survival of more than 95% at 15 to 20 years.
      The reported Indian experience of this knee is limited to 5 years. Our aim was to
      report the clinical and radiological results of the LCS RP TKA design in the
      Indian population with a minimum followup of 10 years. MATERIALS AND METHODS:
      Fifty-five LCS knees (45 patients) operated between February 1997 and October
      2001 were evaluated retrospectively. LCS design was generally selected if the
      patient was young (<=65 years of age), active and had no severe deformity. There
      were 40 female (88.9%) and 5 male (11.1%) patients; 47 knees had osteoarthritis
      (85.5%) and 8 knees had rheumatoid arthritis (14.5%). Knee Society Scores (KSS)
      and outcome questionnaire were filled at followup and radiographs were analyzed
      using Knee Society radiographic evaluation and scoring system. RESULTS: Of 45
      patients (55 knees) enrolled, 37 patients (44 knees; 80%) were available for
      followup at 10 years. Average age was 59.6 years (range 40 to 77). Minimum
      followup was 10 years (average 12.3 years; range 10 to 15.3 years.). Three knees
      (6.8%) had been revised, one each for aseptic loosening, bearing dislocation and
      infection. Mean preoperative KSS of 33 improved to 91 postoperatively. Mean
      preoperative functional score of 45 improved to 76 postoperatively. Mean
      preoperative flexion of 113 degrees  (90 degrees -140 degrees ) reduced to 102
      degrees  (80 degrees -135 degrees ) postoperatively. Erratic femoral rollback and
      tighter flexion gap to prevent spin out are the probable factors for decreased
      postoperative range of motion. Five (12%) patients could sit cross-legged and sit
      on the floor. Anterior knee pain was present in 4.6% (2/44 knees). The survival
      was 93.2% at 12.3 years. One patient (1.8%) had spin-out of the rotating bearing.
      No knee had osteolysis or progressive radiolucent lines on X-rays. CONCLUSION:
      LCS implant has given good survival (93.2% at 12.3 years) with low rates of spin
      out and anterior knee pain and no incidence of osteolysis. Limited flexion post
      surgery (104 degrees ) with only 12% managing to sit cross legged on the floor is
      a drawback.

PMID- 23532674
TI  - Visceral Leishmaniasis Eradication is a Reality: Data from a Community-based
      Active Surveillance in Bangladesh.
AB  - More than 20 million people in Bangladesh are considered at risk of developing
      visceral leishmaniasis (VL). A community-based active surveillance was conducted
      in eight randomly selected villages in a highly endemic area of Bangladesh from
      2006 to 2008. A total of 6,761 individuals living in 1,550 mud-walled houses were
      included in the active surveillance. Rapid rK39 dipstick tests were conducted
      throughout the study period to facilitate the case diagnosis. Individuals with
      previous or current clinical leishmaniasis were identified on the basis of the
      case definition of the VL elimination program. Untreated cases of suspected VL
      were referred to the hospital for treatment. Socioeconomic and environmental
      information including bed net use was also collected. In 2006, the annual
      incidence of clinical leishmaniasis in the study area was 141.9 cases per 10,000
      population, which was significantly increased by the following year owing to
      community-based active surveillance for case detection and reporting. However,
      early case detection and early referral for treatment led to a significant
      decrease in incidence in 2008. This study suggests that community-based active
      surveillance using a simple diagnostic tool might play a role in achieving the
      goal of the VL elimination program.

PMID- 23532675
TI  - Actinomyces meyeri: from "lumpy jaw" to empyema.
AB  - While the most common presentation of actinomycosis is cervicofacial disease, or
      "lumpy jaw syndrome," Actinomyces meyeri has a predilection for pulmonary disease
      as well as dissemination to distant organs. We describe a 61-year-old Caucasian
      male with a relapsing-remitting mandibular sinus tract who would go on to develop
      weight loss, dyspnea, and a cough productive of malodorous sputum. Imaging
      revealed a right lower lobe pneumonia and a large left sided empyema. He
      underwent thoracotomy and decortication on the left side, and 1 L of foul
      smelling purulent fluid was drained. Culture grew Actinomyces meyeri. He
      completed an extended antibiotic course and had his teeth extracted with good
      clinical outcome. 

PMID- 23532676
TI  - Pharmacological postconditioning by bolus injection of phosphodiesterase-5
      inhibitors vardenafil and sildenafil.
AB  - Postconditioning enables cardioprotection against ischemia/reperfusion injury
      either by application of short, repetitive ischemic periods or by pharmacological
      intervention prior to reperfusion. Pharmacological postconditioning has been
      described for phosphodiesterase-5 inhibitors when the substances were applied as
      a permanent infusion. For clinical purposes, application of a bolus is more
      convenient. In a rat heart in situ model of ischemia reperfusion vardenafil or
      sildenafil were applied as a bolus prior to reperfusion. Cardioprotective effects
      were found over a broad dosage range. In accordance with current hypotheses on
      pharmacological postconditioning signaling, the protective effect was mediated by
      extracellular signal-regulated kinase and protein kinase C pathway.
      Interestingly, the extent of protection was independent of the concentration
      applied for both substances. Full protection comparable to ischemic
      postconditioning was reached with half-maximal human equivalence dose. In
      contrast, mean arterial pressure dropped upon bolus application in a dose
      dependent manner. Taken together, the current study extends previous findings
      obtained in a permanent infusion model to bolus application. This is an important
      step toward clinical application of pharmacological postconditioning with
      sildenafil and vardenafil, especially because the beneficial effects were proven
      for concentrations with reduced hemodynamic side effects compared to the dosage
      applied for erectile dysfunction treatment.

PMID- 23532678
TI  - Urethral pressure reflectometry during intra-abdominal pressure increase-an
      improved technique to characterize the urethral closure function in continent and
      stress urinary incontinent women.
AB  - AIM: to assess the urethral closure function by urethral pressure reflectometry
      (UPR) during intra-abdominal pressure-increase in SUI and continent women.
      METHODS: Twenty-five urodynamically proven SUI women and eight continent
      volunteer women were assessed by ICIQ-SF, pad-weighing test, incontinence diary,
      and UPR. UPR was conducted during resting and increased intra-abdominal pressure
      (P(Abd)) by straining. Related values of P(Abd) and urethral opening pressure
      (P(o)) were plotted into an abdomino-urethral pressuregram. Linear regression of
      the values was conducted, and the slope of the line ("APIR") and the intercept
      with the y-axis found. By the equation of the line, Po was calculated for various
      values of P(Abd), for example, 50 cm H2O (P(o-Abd 50)). RESULTS: The resting P(o)
      (P(o-rest)) and APIR, respectively, significantly differed in SUI and continent
      women but could not separate the two groups. The urethral closure equation (UCE)
      based on P(o-rest) and APIR provided a more detailed characterization of a
      woman's closure function based on the permanent closure forces (primarily
      generated by the urethral sphincteric unit) and the adjunctive closure forces
      (primarily generated by the support system). P(o-Abd 50) and UCE, respectively,
      which express the combined permanent and adjunctive closure forces and estimate
      the efficiency of the closure function, separated SUI and continent women and
      were highly significantly negatively correlated with ICIQ-SF, pad test, and the
      number of incontinence episodes. CONCLUSIONS: New parameters for characterization
      of the urethral closure function and possible dysfunctions and its efficiency
      were provided. P(o-Abd 50) and UCE may be used as diagnostic tests and severity
      measures.

PMID- 23532677
TI  - Inhibition of thyroid hormone receptor alpha1 impairs post-ischemic cardiac
      performance after myocardial infarction in mice.
AB  - Thyroid hormone receptor alpha1 (TRalpha1) is shown to be critical for the
      maturation of cardiomyocytes and for the cellular response to stress. TRalpha1 is
      altered during post ischemic cardiac remodeling but the physiological
      significance of this response is not fully understood. Thus, the present study
      explored the potential consequences of selective pharmacological inhibition of
      TRalpha1 on the mechanical performance of the post-infarcted heart. Acute
      myocardial infarction was induced in mice (AMI), while sham operated animals
      served as controls (SHAM). A group of mice was treated with debutyl-dronedarone
      (DBD), a selective TRalpha1 inhibitor (AMI-DBD). AMI resulted in low T3 levels in
      plasma and in down-regulation of TRalpha1 and TRbeta1 expression. Left
      ventricular ejection fraction (LVEF%) was significantly reduced in AMI [33 (SEM
      2.1) vs 79(2.5) in SHAM, p < 0.05] and was further declined in AMI-DBD [22(1.1)
      vs 33(2.1), respectively, p < 0.05]. Cardiac mass was increased in AMI but not in
      AMI-DBD hearts, resulting in significant increase in wall tension index. This
      increase in wall stress was accompanied by marked activation of p38 MAPK, a
      kinase that is sensitive to mechanical stretch and exerts negative inotropic
      effect. Furthermore, AMI resulted in beta-myosin heavy chain overexpression and
      reduction in the ratio of SR(Ca)ATPase to phospholamban (PLB). The latter further
      declined in AMI-DBD mainly due to increased expression of PLB. AMI induces
      downregulation of thyroid hormone signaling and pharmacological inhibition of
      TRalpha1 further depresses post-ischemic cardiac function. p38 MAPK and PLB may,
      at least in part, be involved in this response.

PMID- 23532679
TI  - Prospective multicenter clinical trial of immunosuppressive drug withdrawal in
      stable adult liver transplant recipients.
AB  - Lifelong immunosuppression increases morbidity and mortality in liver
      transplantation. Discontinuation of immunosuppressive drugs could lessen this
      burden, but the safety, applicability, and clinical outcomes of this strategy
      need to be carefully defined. We enrolled 102 stable liver recipients at least 3
      years after transplantation in a single-arm multicenter immunosuppression
      withdrawal trial. Drugs were gradually discontinued over a 6 to 9-month period.
      The primary endpoint was the development of operational tolerance, defined as
      successful immunosuppressive drug cessation maintained for at least 12 months
      with stable graft function and no histopathologic evidence of rejection. Out of
      the 98 recipients evaluated, 57 rejected and 41 successfully discontinued all
      immunosuppressive drugs. In nontolerant recipients rejection episodes were mild
      and resolved over 5.6 months (two nontolerant patients still exhibited mild
      gradually improving cholestasis at the end of follow-up). In tolerant recipients
      no progressive clinically significant histological damage was apparent in follow
      up protocol biopsies performed up to 3 years following drug withdrawal. Tolerance
      was independently associated with time since transplantation (odds ratio [OR]
      1.353; P = 0.0001), recipient age (OR 1.073; P = 0.009), and male gender (OR
      4.657; P = 0.016). A predictive model incorporating the first two clinical
      variables identified subgroups of recipients with very high (79%), intermediate
      (30%-38%), and very low (0%) likelihood of successful withdrawal. CONCLUSION:
      When conducted at late timepoints after transplantation, immunosuppression
      withdrawal is successful in a high proportion of carefully selected liver
      recipients. A combination of clinical parameters could be useful to predict the
      success of this strategy. Additional prospective studies are now needed to
      confirm these results and to validate clinically applicable diagnostic
      biomarkers.

PMID- 23532680
TI  - A Cross Sectional Study of Public Knowledge and Attitude towards Antibiotics in
      Putrajaya, Malaysia.
AB  - OBJECTIVE: The objective of the study was to assess public knowledge and
      attitudes regarding antibiotic utilization in Putrajaya, Malaysia. METHODS: A
      self-administered questionnaire survey was conducted among public attending a
      local hospital. The four-part questionnaire collected responses on demographic
      characteristics, recent use of antibiotics, knowledge and attitude statements.
      Cronbach's alpha for knowledge and attitude statements were 0.68 and 0.74
      respectively. Only questionnaires with complete responses were analysed. General
      linear modelling was used to identify demographic characteristics which
      contributed significantly to knowledge and attitude. Multiple logistic regression
      was used to determine the adjusted odds ratios of obtaining an inappropriate
      response for each knowledge and attitude statement. The relationship between
      antibiotic knowledge and attitude was examined using Pearson's correlation and
      correlation between related statements was performed using the Chi-square test.
      In all statistical analyses, a p-value of < 0.05 was considered statistically
      significant. RESULTS: There was positive correlation (p<0.001) between mean
      knowledge (6.07+/-2.52) and attitude scores (5.59+/-1.67). Highest education
      level (p<0.001) and healthcare-related occupation (p=0.001) contributed
      significantly to knowledge. Gender (p=0.010), race (p=0.005), highest education
      level (p<0.001), employment status (p=0.016) and healthcare-related occupation
      (p=0.005) contributed significantly to attitude. The differences in score between
      demographic groups were small. Misconceptions that antibiotics would work on both
      bacterial and viral infections were reported. Approximately three quarters of
      respondents expected antibiotics for treatment of coughs and colds. Close to two
      thirds (60%) believed that taking antibiotics would improve recovery. Several
      demographic groups were identified as 'high risk' with respect to gaps in
      knowledge and attitude. CONCLUSIONS: This study has identified important
      knowledge and attitude gaps as well as people 'at risk'. These findings would be
      useful in strategizing targeted antibiotic awareness campaigns and patient
      counselling.

PMID- 23532681
TI  - Enhanced electrochemical performance of ZnO-loaded/porous carbon composite as
      anode materials for lithium ion batteries.
AB  - ZnO-loaded/porous carbon (PC) composites with different ZnO loading amounts are
      first synthesized via a facile solvothermal method and evaluated for anode
      materials of lithium ion batteries. The architecture and the electrochemical
      performance of the as-prepared composites are investigated through structure
      characterization and galvanostatic charge/discharge test. The ZnO-loaded/PC
      composites possess a rich porous structure with well-distributed ZnO particles
      (size range: 30-100 nm) in the PC host. The one with 54 wt % ZnO loading contents
      exhibits a high reversible capacity of 653.7 mA h g(-1) after 100 cycles. In
      particular, a capacity of 496.8 mA h g(-1) can be reversibly obtained when cycled
      at 1000 mA g(-1). The superior lithium storage properties of the composite may be
      attributed to its nanoporous structure together with an interconnected network.
      The modified interfacial reaction kinetics of the composite promotes the
      intercalation/deintercalation of lithium ions and the charge transfer on the
      electrode. As a result, the enhanced capacity of the composite electrode is
      achieved, as well as its high rate capability.

PMID- 23532683
TI  - Tolerance and toxicity of primary radiation therapy in the management of
      seropositive HIV patients with squamous cell carcinoma of the head and neck.
AB  - OBJECTIVES/HYPOTHESIS: To report tolerance and toxicity of radiotherapy (RT) with
      or without chemotherapy in HIV seropositive patients with squamous cell carcinoma
      of the head and neck (SCCHN). METHODS: This is a single institution retrospective
      study of 73 HIV seropositive patients with SCCHN treated from January 1997
      through 2010. Stages I, II, III, and IV were 8%, 10%, 24%, and 58%, respectively.
      The median age at RT, HIV diagnosis. and the duration of HIV seropositive were 51
      (32-72), 34 (25-50), and 11 (6-20) years, respectively. Patients were treated
      definitively with RT alone (35%) or concurrent chemo-RT (65%). Median dose of 70
      Gy (66-70) was delivered to the gross disease. Median duration of treatment was
      52 (49-64) days. Fifty patients (70%) were on HAART. RESULTS: RT+/- chemotherapy
      induced acute toxicity was: median weight loss 20 pounds (6-40), 100% developed
      dysgeusia and xerostomia (grades 1-3). Acute mucositis and dysphagia/odynophagia
      grades <= 2 and 3 were 83% and 17%, respectively. Treatment breaks in excess of
      10, 7, and 3 days were found in 5%, 13%, and 15% of patients, respectively. With
      a median follow-up of 4 years (2-12) the RT +/-chemotherapy induced late
      dysphagia and xerostomia grades >2 were 26% and 23% of patients, respectively.
      CONCLUSION: Our data show that primary RT +/-chemotherapy for HIV seropositive
      SCCHN is less tolerated compared to the historical data for SCCHN without HIV.
      LEVEL OF EVIDENCE: 2b.

PMID- 23532682
TI  - Inflammatory response following diffuse axonal injury.
AB  - DAI is a leading cause of the patient's death or lasting vegetable state
      following severe TBI, and up to now the detailed mechanism of axonal injury after
      head trauma is still unclear. Inflammatory responses have been proved to be an
      important mechanism of neural injury after TBI. However, most of these studies
      are concerned with focal cerebral injury following head trauma. In contrast to
      focal injury, studies on the inflammatory reaction following DAI are only
      beginning. And in this article, we aimed to review such studies. From the studies
      reviewed, immune response cells would become reactive around the sites of axonal
      injury after DAI. Besides, the concentrations of several important inflammatory
      factors, such as IL-1 family, IL-6 and TNF-alpha, increased after DAI as well,
      which implies the participation of inflammatory responses. It can be concluded
      that inflammatory responses probably participate in the neural injury in DAI, but
      at present the study of inflammatory responses following DAI is still limited and
      the clear effects of inflammatory response on axonal injury remain to be more
      explored.

PMID- 23532685
TI  - Angiotensin II Receptor Antagonism Reduces Transforming Growth Factor Beta and
      Smad Signaling in Thoracic Aortic Aneurysm.
AB  - BACKGROUND: The expression of transforming growth factor beta (TGF-beta) and
      Smad3 regulates extracellular matrix homeostasis and inflammation in aortic
      aneurysms. The expression of Smad3 depends on signaling by angiotensin II (AngII)
      receptor pathways through TGF-beta receptor-dependent and -independent pathways.
      METHODS: To determine the expression of AngII type 1 (AT1R) and type 2 receptors
      (AT2R), TGF-beta, and Smad3 in thoracic aortic aneurysms, we performed
      immunohistochemistry testing on tissue and cultured cells derived from subjects
      with Marfan syndrome (MFS) and bicuspid aortic valve (BAV) malformation and from
      normal aortas of subjects who were organ donors. RESULTS: MFS and BAV aneurysm
      tissue showed enhanced accumulation of TGF-beta and Smad3 in vascular smooth
      muscle cells (VSMCs) and in inflammatory cells in the subintimal layer and tunica
      media. The normal aortic wall exhibited minimal TGF-beta and Smad3 staining.
      Cultured VSMCs from MFS and BAV samples showed nuclear Smad3 and strong
      cytoplasmic TGF-beta expression in the cytoplasmic vesicles. In control cells,
      Smad3 was located mainly in the cytoplasm, and weak cytoplasmic TGF-beta was
      distributed with a pattern similar to that of the aneurysm-derived cells.
      Compared to normal aorta cells, AT1R and AT2R expression was increased in both
      aneurysm types. Treatment of cultured VSMCs with the AT1R antagonist losartan
      caused both reduced TGF-beta vesicle localization and nuclear expression of
      Smad3. CONCLUSIONS: Increased TGF-beta and Smad3 expression in aneurysm tissue
      and cultured VSMCs is consistent with aberrant TGF-beta expression and the
      activation of Smad3 signaling. Losartan-mediated reduction in TGF-beta expression
      and the cytoplasmic localization of Smad3 support a role for AT1R antagonism in
      the inhibition of aneurysm progression.

PMID- 23532684
TI  - Age-related changes in brain structural covariance networks.
AB  - Previous neuroimaging studies have suggested that cerebral changes over normal
      aging are not simply characterized by regional alterations, but rather by the
      reorganization of cortical connectivity patterns. The investigation of structural
      covariance networks (SCNs) using voxel-based morphometry is an advanced approach
      to examining the pattern of covariance in gray matter (GM) volumes among
      different regions of the human cortex. To date, how the organization of critical
      SCNs change during normal aging remains largely unknown. In this study, we used
      an SCN mapping approach to investigate eight large-scale networks in 240 healthy
      participants aged 18-89 years. These participants were subdivided into young (18
      23 years), middle aged (30-58 years), and older (61-89 years) subjects. Eight
      seed regions were chosen from widely reported functional intrinsic connectivity
      networks. The voxels showing significant positive associations with these seed
      regions were used to describe the topological organization of an SCN. All of
      these networks exhibited non-linear patterns in their spatial extent that were
      associated with normal aging. These networks, except the primary motor network,
      had a distributed topology in young participants, a sharply localized topology in
      middle aged participants, and were relatively stable in older participants. The
      structural covariance derived using the primary motor cortex was limited to the
      ipsilateral motor regions in the young and older participants, but included
      contralateral homologous regions in the middle aged participants. In addition,
      there were significant between-group differences in the structural networks
      associated with language-related speech and semantics processing, executive
      control, and the default-mode network (DMN). Taken together, the results of this
      study demonstrate age-related changes in the topological organization of SCNs,
      and provide insights into normal aging of the human brain.

PMID- 23532686
TI  - Pharmacokinetics and pharmacodynamics of the antiplatelet combination aspirin
      (acetylsalicylic acid) plus extended-release dipyridamole are not altered by
      coadministration with the potent CYP2C19 inhibitor omeprazole.
AB  - BACKGROUND: The fixed-dose combination of aspirin (acetylsalicylic acid) 25 mg
      plus extended-release dipyridamole 200 mg (ASA+ER-DP) is used for long-term
      secondary stroke prevention in patients who have experienced non-cardioembolic
      stroke or transient ischemic attack. Although the theoretical risk is low that
      the antiplatelet activity of ASA+ER-DP will be affected by concomitant use of a
      proton pump inhibitor (PPI), no formal drug-drug interaction studies have been
      conducted. OBJECTIVE: This study aimed to determine whether the PPI omeprazole
      influences the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of ASA+ER
      DP. STUDY DESIGN AND SETTING: This was a randomized, open-label, multiple-dose,
      crossover, drug-drug interaction study carried out in a clinical trial unit.
      PARTICIPANTS: Sixty healthy male and female volunteers aged 18-50 years were
      included in the study. INTERVENTION: Participants were randomized to one of two
      treatment sequences (ABCD or CDAB), each comprising four 7-day treatments with a
      washout of >=14 days between the second and third treatments. Treatment A=ASA+ER
      DP 25 mg/200 mg (Aggrenox(r)) twice daily (BID) alone; B=ASA+ER-DP 25 mg/200 mg
      BID+omeprazole (Prilosec(r)) 80 mg once daily (QD) following ASA+ER-DP alone for
      7 days; C=omeprazole 80 mg QD alone; D=omeprazole 80 mg QD+ASA+ER-DP 25 mg/200 mg
      BID following omeprazole alone for 7 days. MAIN OUTCOME MEASURES: The main
      outcome measures were systemic PK exposure to ER-DP and ASA inhibition of
      arachidonic acid-induced platelet aggregation. RESULTS: Systemic exposure to ER
      DP was similar with and without omeprazole, based on steady-state area under the
      concentration-time curve (AUC) from 0 to 12 h (AUC0-12,ss, ng.h/mL) and maximum
      plasma concentration (Cmax,ss, ng/mL). For the treatment comparison D versus A,
      the percent mean ratios were 96.38 (90% confidence interval [CI] 90.96-102.13)
      for AUC0-12,ss and 92.03 (86.95-97.40) for Cmax,ss. The ER-DP concentration
      versus time profiles were nearly superimposable. There was no effect on the PDs
      of the ASA component: the extent of ASA inhibition of arachidonic acid-induced
      platelet aggregation was almost identical with and without omeprazole, with a
      percent mean ratio for treatment D versus A = 99.02 (90 % CI 98.32-99.72) at 4 h
      after last dose. All treatments were well tolerated. CONCLUSION: The PK and PD
      behavior of ASA + ER-DP was not altered by concurrent administration of
      omeprazole.

PMID- 23532687
TI  - Predicting the impact of polypill use in a metabolic syndrome population: an
      effectiveness and cost-effectiveness analysis.
AB  - BACKGROUND: Individuals with metabolic syndrome (MetS) are at increased risk of
      cardiovascular disease (CVD), often requiring combination drug therapy for
      control of risk factors and subsequent risk reduction. This study aims to compare
      the long-term effectiveness and cost effectiveness of the polypill (a multi
      component tablet), and its components (alone or in combination), in a MetS
      population. METHODS AND RESULTS: A Markov state transition model, using
      individual subject data from the Australian Diabetes, Obesity and Lifestyle
      study, was constructed to simulate the effects of the treatment versus no
      treatment on CVD events, and costs over 10 years. In 1,991 individuals classified
      as MetS and free of existing diabetes mellitus or CVD, treatment with the
      polypill (or its components) was effective at reducing cardiovascular events
      [statin: 171, aspirin (actetylsalicylic acid): 201, antihypertensive: 186 per
      1,000 individuals]. The more drug therapies employed the greater the reduction,
      with the polypill reducing up to 351 cardiovascular events per 10,000
      individuals. Cost-effectiveness analyses were sensitive to drug treatment costs
      and effectiveness of treatment. At a cost of AUD$42 per person per annum, aspirin
      was considered cost saving. All other treatment strategies, including the
      polypill, were not cost effective. CONCLUSION: The polypill is likely to be
      effective in the reduction of cardiovascular events in a MetS population. It is,
      however, not cost effective. Nevertheless, in a high-risk population, among whom
      combination therapy is often prescribed, the polypill is likely to be more cost
      effective than antihypertensive therapy alone or dual therapy with a statin and
      antihypertensive combination.

PMID- 23532688
TI  - Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and
      combined HCC-CC (CHC) with each other based on microarray dataset.
AB  - Liver carcinomas have been classified into three types: hepatocellular carcinoma
      (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC). We aim to find the
      common and different characteristic of these three types of liver cancer. The
      gene expression profiling of HCC, CC, and CHC were compared with each other, and
      enrichment pathways and processes in these three liver cancers were also
      identified. Using GSE15765 datasets downloaded from NCBI GEO database, the gene
      expression profiling of HCC, CC, and CHC were compared with each other (HCC
      compared with CC, HCC compared with CHC, and CC compared with HCC). Then, the
      differentially expressed genes (DEGs) were identified in these three groups
      respectively, and three PPI networks were constructed for DEGs in each group.
      Subsequently, the clusters in these networks were identified and further analyzed
      by ClusterONE and MCODE. Finally, gene set enrichment analysis enrichment
      analysis was performed to illustrate altered pathways and processes for each type
      of liver cancer. A total of 112, 530, and 64 DEGs were identified in three
      groups, respectively, and three PPI networks were constructed respectively for
      the corresponding group. Through the cluster analysis, we found some new
      differential marker genes for distinguishing the difference between these three
      types of liver cancer. We also indicated that we can distinguish HCC with CC
      through altered pathways and processes. Our findings develop new biomarkers for
      categorizing the primary liver cancer and may improve patient prognosis of these
      cancers. However, further validation is required since our results were based on
      microarray data derived from a small sample size.

PMID- 23532690
TI  - A surveillance model for human avian influenza with a comprehensive surveillance
      system for local-priority communicable diseases in South sulawesi, indonesia.
AB  - The government of Indonesia and the Japan International Cooperation Agency
      launched a three-year project (2008-2011) to strengthen the surveillance of human
      avian influenza cases through a comprehensive surveillance system of local
      priority communicable diseases in South Sulawesi Province. Based on findings from
      preliminary and baseline surveys, the project developed a technical protocol for
      surveillance and response activities in local settings, consistent with national
      guidelines. District surveillance officers (DSOs) and rapid-response-team members
      underwent training to improve surveillance and response skills. A network-based
      early warning and response system for weekly reports and a short message service
      (SMS) gateway for outbreak reports, both encompassing more than 20 probable
      outbreak diseases, were introduced to support existing paper-based systems. Two
      further strategies were implemented to optimize project outputs: a simulation
      exercise and a DSO-centered model. As a result, the timeliness of weekly reports
      improved from 33% in 2009 to 82% in 2011. In 2011, 65 outbreaks were reported
      using the SMS, with 64 subsequent paper-based reports. All suspected human avian
      influenza outbreaks up to September 2011 were reported in the stipulated format.
      A crosscutting approach using human avian influenza as the core disease for
      coordinating surveillance activities improved the overall surveillance system for
      communicable diseases.

PMID- 23532689
TI  - Clinicopathological significance of BTF3 expression in colorectal cancer.
AB  - Basic transcription factor 3 (BTF3) is a general RNA polymerase II transcription
      factor and is also involved in apoptosis regulation. Increasing evidence shows
      that BTF3 is aberrantly expressed in several kinds of malignancies, but there is
      no study to analyze BTF3 expression in colorectal cancer (CRC) patients. Applying
      immunohistochemistry, we detected BTF3 in CRCs (n = 156), the corresponding
      distant (n = 42), adjacent normal mucosa (n = 96), lymph node metastases (n =
      35), and analyzed its relationships with clinicopathological and biological
      variables. Our results showed that BTF3 staining significantly increased from
      distant or adjacent normal mucosa to primary CRCs (p < 0.0001) or metastases (p =
      0.002 and p < 0.0001). BTF3 was higher in distal cancers than in proximal cancers
      (57 % vs. 39 %, p = 0.041). It also showed stronger staining in primary CRCs
      stage I and II than that in stage III and IV (64 % vs. 35 %, p = 0.0004), or
      metastases (64 % vs. 29 %, p = 0.004). Cancers with better differentiation had a
      higher expression than those with worse differentiation (56 % vs. 37 %, p =
      0.031). There were positive correlations of BTF3 expression with nuclear factor
      kappa B (NF-kappaB), RAD50, MRE11, NBS1, and AEG-1 (p < 0.05). In conclusion,
      BTF3 overexpression may be an early event in CRC development and could be useful
      biomarker for the early stage of CRCs. BTF3 has positive correlations with NF
      kappaB, RAD50, MRE11, NBS1 and AEG-1, and might influence complex signal pathways
      in CRC.

PMID- 23532691
TI  - Senior environments: when we become them.

PMID- 23532692
TI  - Design considerations for aging populations.

PMID- 23532693
TI  - Can Better Outdoor Environments Lead to Cost Benefits in Assisted Living
      Facilities Through Increased Word-of-Mouth Referrals?
AB  - OBJECTIVE: This study explores how better outdoor environments may produce cost
      benefits for assisted living providers by raising occupancy levels through
      increased resident satisfaction and word-of-mouth referrals. BACKGROUND: Older
      adults who spend even minimal time outdoors may reap substantial health benefits.
      However, many existing outdoor areas in assisted living facilities are reportedly
      underutilized, in part because of design issues. Providers may be more willing to
      improve outdoor areas if they produce cost benefits for provider organizations.
      METHODS: This study used data from a recent assisted living survey to assess the
      relationship between satisfaction with outdoor spaces, time spent outdoors, and
      resulting improvements in mood. A financial analysis was developed to estimate
      potential benefits from improved outdoor areas attributable to increased
      occupancy and decreased marketing costs associated with increased word-of-mouth
      referrals. RESULTS: Increasing resident satisfaction with outdoor areas (from
      approximately 29% to 96%) results in residents spending more time outdoors
      (increase of 11/2 hours per week per resident) and improved psychological well
      being (12% increase in feeling better). This greater overall satisfaction leads
      to 8% more residents willing to refer potential residents to their community.
      Because word-of-mouth referrals by current residents are a major factor in
      resident recruitment, improving outdoors areas leads to an estimated 4% increase
      in new residents, resulting in over $170,000 of increased revenue per year for a
      community of 100 residents. CONCLUSIONS: Improved outdoor space can provide
      substantial cost benefits for assisted living providers. Increasing resident well
      being and satisfaction, and thereby generating additional word-of-mouth
      referrals, can result in higher occupancy levels. KEYWORDS: Outdoor environments,
      assisted living, cost benefits, resident satisfaction, occupancy levels, seniors,
      rental income, word-of-mouth referralPreferred Citation: Rodiek, S., Boggess, M.
      M., Lee, C., Booth, G. J., & Morris, A. (2013). Can better outdoor environments
      lead to cost benefits in assisted living facilities through increased word-of
      mouth referrals? Health Environments Research & Design Journal 6(2), pp. 12-26.

PMID- 23532694
TI  - The effect of garden designs on mood and heart output in older adults residing in
      an assisted living facility.
AB  - OBJECTIVE: The objective of this study is to trace short-term changes in mood and
      heart function in elderly individuals in response to exposure to different
      landscaped spaces. BACKGROUND: Nineteen elderly but cognitively intact residents
      of an assisted living facility participated in the study. They were exposed to
      three landscaped spaces: a Japanese style garden, an herb garden, and a simple
      landscaped area planted with a single tree. METHODS: To assess the effect of
      different landscaped spaces on older adults, individuals were monitored for mood
      and cardiac function in response to short exposures to spaces. Mood state was
      assessed using Profile of Mood States (POMS) before and after viewing the spaces.
      Cardiac output was assessed using a portable electrocardiograph monitor before
      and during the viewing. RESULTS: We found that the structured gardens evoked
      greater responses in all outcome measures. Scores on the POMS improved after
      observation of the two organized gardens compared to responses to the simple
      landscaped space with a single tree. During the observation period, heart rate
      was significantly lower in the Japanese garden than in the other environments,
      and sympathetic function was significantly lower as well. CONCLUSIONS: We
      conclude that exposure to organized gardens can affect both the mood and cardiac
      physiology of elderly individuals. Our data further suggest that these effects
      can differ depending on the types of landscape to which an individual is exposed.
      KEYWORDS: Elderly, Japanese garden, herb garden, heart rate, mood, healing
      environmentPreferred Citation: Goto, S., Park, B-J., Tsunetsugu, Y., Herrup, K.,
      & Miyazaki, Y. (2013). The effect of garden designs on mood and heart output in
      older adults residing in an assisted living facility. Health Environments
      Research & Design Journal 6(2), pp 27-42.

PMID- 23532695
TI  - An investigation of noncompliant toilet room designs for assisted toileting.
AB  - OBJECTIVE: By comparing an Americans with Disabilities Act Accessibility
      Guidelines (ADAAG) compliant design with alternative designs, this pilot study
      resulted in recommendations for designing patient bathrooms to facilitate
      assisted toileting. BACKGROUND: The ADA Accessibility Guidelines were developed
      primarily to address the needs of disabled populations, such as returning Vietnam
      veterans, with sufficient upper body strength to transfer independently directly
      from a wheelchair to the toilet. However, the majority of older persons with
      disabilities (90%) stand to transfer to the toilet, rather than laterally moving
      from the wheelchair to the toilet. METHODS: The research used a repeated measures
      research design to evaluate caregiver responses during assisted toileting for
      various toilet configurations. The study included 20 patients who were
      transferred onto and off of a toilet for each of four different configurations by
      one or two caregivers. Toileting trials were videotaped and analyzed by an
      occupational therapist. Additionally, caregivers completed five-question, self
      report surveys after each toileting trial. RESULTS: Survey data indicate that
      staff members prefer the largest of the tested configurations, where the
      centerline of the toilet is 30 inches from the sidewall, rather than the 18
      inches required by the ADAAG, and where there are two fold-down grab bars
      provided. Caregivers perceived the grab bar locations as better for helping them
      safely transfer subjects in a modified (non-ADAAG) configuration, and also that
      the grab bar style in a modified configuration (non-ADAAG) improved safety when
      transferring subjects. CONCLUSIONS: Although caregivers were observed to safely
      transfer residents to and from the toilet for all configurations tested,
      regulations regarding accessibility of patient bathrooms should acknowledge the
      perceived benefits of increasing the distance from the sidewall to the centerline
      of the toilet to as much as 30 inches and allowing two fold-down grab bars
      instead of the required sidewall and back-wall grab bars. KEYWORDS: ADA, toilet
      room design, healthcare design, evidence-based design, human factors, safety,
      staffPreferred Citation: Sanford, J., & Bosch, S. (2013). An investigation of
      noncompliant toilet room designs for assisted toileting. Health Environments
      Research & Design Journal 6(2), pp 43-57.

PMID- 23532696
TI  - Process simulation during the design process makes the difference: process
      simulations applied to a traditional design.
AB  - OBJECTIVE: The objective is evaluation of a traditionally designed operating room
      using simulation of various surgical workflows. BACKGROUND: A literature search
      showed that there is no evidence for an optimal operating room layout regarding
      the position and size of an ultraclean ventilation (UCV) canopy with a separate
      preparation room for laying out instruments and in which patients are induced in
      the operating room itself. Neither was literature found reporting on process
      simulation being used for this application. Many technical guidelines and designs
      have mainly evolved over time, and there is no evidence on whether the proposed
      measures are also effective for the optimization of the layout for workflows.
      METHODS: The study was conducted by applying observational techniques to
      simulated typical surgical procedures. Process simulations which included
      complete surgical teams and equipment required for the intervention were carried
      out for four typical interventions. Four observers used a form to record
      conflicts with the clean area boundaries and the height of the supply bridge.
      Preferences for particular layouts were discussed with the surgical team after
      each simulated procedure. RESULTS: We established that a clean area measuring 3 *
      3 m and a supply bridge height of 2.05 m was satisfactory for most situations,
      provided a movable operation table is used. The only cases in which conflicts
      with the supply bridge were observed were during the use of a surgical robot (Da
      Vinci) and a surgical microscope. During multiple trauma interventions,
      bottlenecks regarding the dimensions of the clean area will probably arise.
      CONCLUSIONS: The process simulation of four typical interventions has led to
      significantly different operating room layouts than were arrived at through the
      traditional design process. KEYWORDS: Evidence-based design, human factors, work
      environment, operating room, traditional design, process simulation, surgical
      workflowsPreferred Citation: Traversari, R., Goedhart, R., & Schraagen, J. M.
      (2013). Process simulation during the design process makes the difference:
      Process simulations applied to a traditional design. Health Environments Research
      & Design Journal 6(2), pp 58-76.

PMID- 23532697
TI  - Moderating role of interior amenities on hospital medical directors' patient
      related work stresses.
AB  - OBJECTIVE: Considering hospital medical directors' work stress, this study aims
      to examine how interior amenities might moderate the effect of work stress on
      their health. BACKGROUND: Previous studies have revealed that hospital medical
      directors-senior physicians in the management positions with high-demand jobs in
      clinical practices and management-had a lower self-rated health. METHODS: This
      was a cross-sectional survey study and 737 hospital medical directors in Taiwan
      were included. A developed and structured questionnaire covered the dimensions of
      patient-related work stress (i.e., physician-patient relationship stress and
      patient condition stress), hospital interior amenities (i.e., indoor plants,
      aquarium, music, art and exhibitions, and private or personalized spaces that are
      common or surround the workplace of healthcare professionals), and self-rated
      health status and health complaints. Hierarchical regressions were performed.
      RESULTS: Hospital medical directors' physician-patient relationship stresses were
      found to have more negative effects on their self-reported health status and
      complaints than do their patient condition stresses; however, only indoor plants
      were found to have moderating effects on their short-term health complaints (p <
      0.05). On the other hand, the hospital medical directors' patient condition
      stresses were negatively related to their short-term health complaints; however,
      music, art and exhibitions, and private or personalized spaces in the workplaces
      had moderating effects (p < 0.05). CONCLUSIONS: Considering the unavoidable
      patient-related work stresses imposed on hospital medical directors, some
      proposed interior amenities can produce buffering effects on work stress to some
      extent. Future studies could focus on finding alternatives to relieve hospital
      medical directors' physician-patient relationship work stresses. KEYWORDS:
      Evidence-based design, physicians, privacy and security, satisfaction, work
      environmentPreferred Citation: Lin, B. Y.-J., Lin, Y.-K., Juan, C.W., Lee, S.,
      Lin, C.-C. (2013). Moderating role of interior amenities on hospital medical
      directors' patient-related work stresses. Health Environments Research & Design
      Journal 6(2), pp 77-92.

PMID- 23532698
TI  - Facility design to reduce hospital-acquired infection.

PMID- 23532699
TI  - Corporate sustainability: the environmental design and human resource management
      interface in healthcare settings.
AB  - Purpose of the Paper: The purpose of this study is to provide healthcare
      organizations with a new perspective for developing strategies to enrich their
      human resource capabilities and improve their performance outcomes. The focus of
      this study is on leveraging the synergy between organizational management
      strategies and environmental design interventions. BACKGROUND: This paper
      proposes a framework for linking the built environment with the human resource
      management system of healthcare organizations. The framework focuses on the
      impact of the built environment regarding job attitudes and behaviors of
      healthcare workers. Research from the disciplines of strategic human resource
      management, resource-based view of firms, evidence-based design, and green
      building are utilized to develop the framework. THEORETICAL FRAMEWORK: The
      positive influence of human resource practices on job attitudes and behaviors of
      employees is one mechanism to improve organizational performance outcomes.
      Organizational psychologists suggest that human resource practices are effective
      because they convey that the organization values employee contributions and cares
      about their well-being. Attention to employee socio-emotional needs can be
      reciprocated with higher levels of motivation and commitment toward the
      organization. In line with these findings, healthcare environmental studies imply
      that physical settings and features can have a positive influence on job
      attitudes and the behavior of caregivers by providing for their physical and
      socio-emotional needs. CONCLUSIONS: Adding the physical environment as a
      complementary resource to the array of human resource practices creates synergy
      in improving caregivers' job attitudes and behaviors and enhances the human
      capital of healthcare firms. KEYWORDS: Staff, evidence-based design,
      interdisciplinary, modeling, perceived organizational supportPreferred Citation:
      Sadatsafavi, H., & Walewski, J. (2013). Corporate sustainability: The
      environmental design and human resource management interface in healthcare
      settings. Health Environments Research & Design Journal 6(2), pp 98-118.

PMID- 23532700
TI  - How to rate the quality of a research paper: introducing a helpful algorithm for
      architects and designers.
AB  - KEYWORDS: Decision-making, evidence-based design, methodology.

PMID- 23532701
TI  - Lean-led hospital design: creating the efficient hospital of the future.

PMID- 23532702
TI  - Genetic structure of introduced populations: 120-year-old DNA footprint of
      historic introduction in an insular small mammal population.
AB  - Wildlife populations have been introduced to new areas by people for centuries,
      but this human-mediated movement can disrupt natural patterns of genetic
      structure by altering patterns of gene flow. Insular populations are particularly
      prone to these influences due to limited opportunities for natural dispersal onto
      islands. Consequently, understanding how genetic patterns develop in island
      populations is important, particularly given that islands are frequently havens
      for protected wildlife. We examined the evolutionary origins and extent of
      genetic structure within the introduced island population of red squirrels
      (Sciurus vulgaris) on the Channel Island of Jersey using mitochondrial DNA
      (mtDNA) control region sequence and nuclear microsatellite genotypes. Our
      findings reveal two different genetic origins and a genetic architecture
      reflective of the introductions 120 years ago. Genetic structure is marked within
      the maternally inherited mtDNA, indicating slow dispersal of female squirrels.
      However, nuclear markers detected only weak genetic structure, indicating
      substantially greater male dispersal. Data from both mitochondrial and nuclear
      markers support historic records that squirrels from England were introduced to
      the west of the island and those from mainland Europe to the east. Although some
      level of dispersal and introgression across the island between the two
      introductions is evident, there has not yet been sufficient gene flow to erase
      this historic genetic "footprint." We also investigated if inbreeding has
      contributed to high observed levels of disease, but found no association. Genetic
      footprints of introductions can persist for considerable periods of time and
      beyond traditional timeframes of wildlife management.

PMID- 23532705
TI  - Basic research: Issues with animal experimentations.
AB  - In vivo studies using the animals are helpful in developing the treatment
      strategies as they are important link between the successful in vitro testing and
      safe human use. Various research projects in the field of fixation of fractures,
      development of newer biomaterials, chemotherapeutic drugs, use of stem cells in
      nonunion of fractures and cartilage defects etc., have hugely depended on animal
      experimentation. The employment of animals in experiments is both scientific and
      ethical issue. There must be reasonable reasons to show that it will
      significantly advance the present knowledge and lead to improvement in care. The
      regulatory bodies exist for humane use and care of animals used for experiments
      e.g., International Council for Laboratory Animal Science, Council for
      International Organizations of Medical Sciences, International Union of
      Biological Sciences, International Committee on Laboratory Animals. In India,
      Indian National Science Academy, Indian Council of Medical Research, National
      Centre for Laboratory Animal Sciences promote high standards of laboratory animal
      quality, care and health. The Committee for the Purpose of Control and
      Supervision on Experiments on Animals guidelines are well defined and is a must
      read document for any one interested to carry out research with animal
      facilities.

PMID- 23532704
TI  - Developmental and architectural principles of the lateral-line neural map.
AB  - The transmission and central representation of sensory cues through the accurate
      construction of neural maps is essential for animals to react to environmental
      stimuli. Structural diversity of sensorineural maps along a continuum between
      discrete- and continuous-map architectures can influence behavior. The
      mechanosensory lateral line of fishes and amphibians, for example, detects
      complex hydrodynamics occurring around the animal body. It triggers innate fast
      escape reactions but also modulates complex navigation behaviors that require
      constant knowledge about the environment. The aim of this article is to summarize
      recent work in the zebrafish that has shed light on the development and structure
      of the lateralis neural map, which is helping to understand how individual
      sensory modalities generate appropriate behavioral responses to the sensory
      context.

PMID- 23532707
TI  - S3 motor branch stimulation failure due to nerve fiber burning at the nerve-wire
      junction: A historical technical note.
AB  - BACKGROUND: Sacral nerve stimulation is a minimally invasive procedure to treat
      spinal cord injured (SCI) patients with overactive bladder syndrome or
      nonobstructive urinary retention that is refractory to conservative treatment.
      METHODS: In this paper, we report a case of traumatic cervical SCI with
      quadriplegia and spastic bladder, which was managed by third sacral motor branch
      stimulation in 1998. RESULTS: In this case, stimulation-induced burning of nerve
      fibers was seen microscopically during the implantation surgery. At 2 weeks after
      the index surgery, the stimulator was removed due to ineffectiveness. We
      hypothesize that the stimulation settings of our stimulator were not appropriate
      for neural stimulation and led to neural destruction, fibrosis, and treatment
      failure. CONCLUSION: The device settings of stimulators used in neural
      stimulation should be appropriate for direct neural stimulation otherwise they
      can lead to neural destruction and treatment failure.

PMID- 23532706
TI  - Brain effect of insulin and clonazepam in diabetic rats under depressive-like
      behavior.
AB  - Diabetes mellitus is characterized by hyperglycemia resulting from defects on
      insulin secretion, insulin action, or both. It has recently become clear that the
      central nervous system is not spared from the deleterious effects of diabetes,
      since diabetic encephalopathy was recognized as a complication of this
      heterogeneous metabolic disorder. There is a well recognized association between
      depression and diabetes, once prevalence of depression in diabetic patients is
      higher than in general population, and clonazepam is being used to treat this
      complication. Oxidative stress is widely accepted as playing a key mediatory role
      in the development and progression of diabetes and its complications. In this
      work we analyzed DNA damage by comet assay and lipid damage in prefrontal cortex,
      hippocampus and striatum of streptozotocin-induced diabetic rats submitted to the
      forced swimming test. It was verified that the diabetic group presented DNA and
      lipid damage in the brain areas evaluated, when compared to the control groups.
      Additionally, a significant reduction of the DNA and lipid damage in animals
      treated with insulin and/or clonazepam was observed. These data suggest that the
      association of these two drugs could protect against DNA and lipid damage in
      diabetic rats submitted to the forced swimming test, an animal model of
      depression. 

PMID- 23532708
TI  - Hashimoto's encephalopathy in the intensive care unit.
AB  - BACKGROUND: Since the first description of Hashimoto's Encephalitis (HE) in 1966
      by Lord Brain, the number of reported cases has continued to increase. In
      addition, cases of status epilepticus have been reported, suggesting a role for
      intensive care unit (ICU) practitioners in taking care of patients with HE.
      METHODS: A retrospective cohort study in ICU patients with HE was performed at
      the University Hospital of Tours, France. RESULTS: Eight HE cases were admitted
      to the ICU between 1/1/2000 and 1/1/2012. Herein, we describe the characteristics
      of the patients, with an emphasis on ICU disease management and its outcome.
      CONCLUSION: ICU practitioners should be aware of this disease, since it can
      include life-threatening presentations.

PMID- 23532709
TI  - Intensity-modulated radiotherapy to the pelvis and androgen deprivation in men
      with locally advanced prostate cancer: a study of adverse effects and their
      relation to quality of life.
AB  - BACKGROUND: To study, adverse effects, quality of life (QoL), fatigue, and mental
      distress when intensity-modulated radiotherapy combined with androgen deprivation
      was applied to the whole pelvis as management of men with locally advanced
      prostate cancer. METHODS: In this prospective follow-up study 91 patients were
      treated by modern pelvic intensity-modulated radiotherapy and followed for 12
      months. The patients completed a questionnaire with well-established instruments
      for adverse effects on urinary, bowel, and sexual function and bother, QoL,
      fatigue, and mental distress before treatment, and at 3 and 12 months follow-up.
      RESULTS: After pelvic intensity-modulated radiotherapy the mean levels of sexual
      urinary and bowel function and bother were significantly reduced from baseline.
      Only urinary bother improved from 3 to 12-month follow-up. The levels of fatigue
      and QoL increased significantly from baseline to 3-month. Mental distress,
      fatigue, and QoL were significantly associated with both urinary and bowel
      function and bother at most time points, while so was not observed for sexual
      bother and function. CONCLUSIONS: Men treated with pelvic intensity-modulated
      radiotherapy and androgen deprivation have significant reductions of all types of
      function and bother at 3 months, with minimal improvement to 12 months except for
      urinary bother. Fatigue possibly due to pelvic intensity-modulated radiotherapy
      increased at follow-ups.

PMID- 23532710
TI  - Impact of external price referencing on medicine prices - a price comparison
      among 14 European countries.
AB  - OBJECTIVES: This study aims to examine the impact of external price referencing
      (EPR) on on-patent medicine prices, adjusting for other factors that may affect
      price levels such as sales volume, exchange rates, gross domestic product (GDP)
      per capita, total pharmaceutical expenditure (TPE), and size of the
      pharmaceutical industry. METHODS: Price data of 14 on-patent products, in 14
      European countries in 2007 and 2008 were obtained from the Pharmaceutical Price
      Information Service of the Austrian Health Institute. Based on the unit ex
      factory prices in EURO, scaled ranks per country and per product were calculated.
      For the regression analysis the scaled ranks per country and product were
      weighted; each country had the same sum of weights but within a country the
      weights were proportional to its sales volume in the year (data obtained from IMS
      Health). Taking the scaled ranks, several statistical analyses were performed by
      using the program "R", including a multiple regression analysis (including
      variables such as GDP per capita and national industry size). RESULTS: This study
      showed that on average EPR as a pricing policy leads to lower prices. However,
      the large variation in price levels among countries using EPR confirmed that the
      price level is not only driven by EPR. The unadjusted linear regression model
      confirms that applying EPR in a country is associated with a lower scaled
      weighted rank (p=0.002). This interaction persisted after inclusion of total
      pharmaceutical expenditure per capita and GDP per capita in the final model.
      CONCLUSIONS: The study showed that for patented products, prices are in general
      lower in case the country applied EPR. Nevertheless substantial price differences
      among countries that apply EPR could be identified. Possible explanations could
      be found through a correlation between pharmaceutical industry and the scaled
      price ranks. In conclusion, we found that implementing external reference pricing
      could lead to lower prices.

PMID- 23532712
TI  - Tic modulation using sensory tricks.
AB  - BACKGROUND: A sensory trick, or geste antagoniste, is defined as a physical
      gesture (such as a touch on a particular body part) that mitigates the production
      of an involuntary movement. This phenomenon is most commonly described as a
      feature of dystonia. Here we present a case of successful modulation of tics
      using sensory tricks. CASE REPORT: A case report and video are presented. The
      case and video demonstrate a 19-year-old male who successfully controlled his
      tics with various sensory tricks. DISCUSSION: It is underappreciated by movement
      disorder physicians that sensory tricks can play a role in tics. Introducing this
      concept to patients could potentially help in tic control. In addition,
      understanding the pathophysiological underpinnings of sensory tricks could help
      in the understanding of the pathophysiology of tics.

PMID- 23532711
TI  - IGF-1 acts as controlling switch for long-term proliferation and maintenance of
      EGF/FGF-responsive striatal neural stem cells.
AB  - BACKGROUND: Long-term maintenance of neural stem cells in vitro is crucial for
      their stage specific roles in neurogenesis. To have an in-depth understanding of
      optimal conditional microenvironmental niche for long-term maintenance of neural
      stem cells (NSCs), we imposed different combinatorial treatment of growth factors
      to EGF/FGF-responsive cells. We hypothesized, that IGF-1-treatment can provide an
      optimal niche for long-term maintenance and proliferation of EGF/FGF-responsive
      NSCs. OBJECTIVE: This study was performed to investigate the cellular morphology
      and growth of rat embryonic striatal tissue derived-NSCs in long-term culture
      under the influence of different combinatorial effects of certain growth factors,
      such as EGF, bFGF, LIF and IGF-1. METHODS: The NSCs were harvested and cultured
      from striatal tissue of 18 days old rat embryos. We have generated neurospheres
      from these NSCs and cultured them till passage 7 (28 days in vitro) under four
      different conditional microenvironments: (A) without growth factor, (B) EGF/bFGF,
      (C) EGF/bFGF/LIF, (D) EGF/bFGF/IGF-1 and (E) EGF/bFGF/LIF/IGF-1. Isolated NSCs
      were characterised by Immunoflouroscence for nestin expression. The cell growth
      and proliferation was evaluated at different time intervals (P1, P3, P5 & P7),
      assessing the metabolic activity based cell proliferation. Apoptosis was studied
      in each of these groups by In situ cell death assay. RESULTS: Our results
      demonstrated certain important findings relevant to long-term culture and
      maintenance of striatal NSC-derived neurospheres. This suggested that IGF-1 can
      induce enhanced cell proliferation during early stages of neurogenesis, impose
      long-term maintenance (up to passage 7) to cultured NSCs and enhance survival
      efficiency in vitro, in the presence of EGF and FGF. CONCLUSIONS: Our findings
      support the hypothesis that the enforcement of IGF-1 treatment to the EGF/FGF
      responsive NSCs, can lead to enhanced cell proliferation during early stages of
      neurogenesis, and an extended life span in vitro. This information will be
      beneficial for improving future therapeutic implication of NSCs, by addressing
      improved in vitro production of NSCs.

PMID- 23532713
TI  - Radiation therapy for Benign Lymphoepithelial Cysts of parotid glands in HIV
      patients.
AB  - OBJECTIVES/HYPOTHESIS: To report the long-term outcomes of radiation therapy
      (RT), and the impact of fractionation size and RT duration on HIV patients with
      Benign Lymphoepithelial Cysts (BLEC) of the parotid glands. METHODS: From January
      2000 to 2011, 30 patients were eligible for our single institution retrospective
      study. Both parotids were treated with 24 Gy via RT. The median age at RT, HIV
      diagnosis, and duration of HIV seropositive was 45 years (28-64), 38 years (23
      53), and 11 years (6-35), respectively. Patients were stratified into two groups.
      Group A and B received 2Gyx12 and 1.5Gyx16, respectively. RESULTS: After a median
      follow-up of 66 months (12-141), the overall response (OvR) was 93% of the
      patients. Specifically, complete response (CR) and partial response (PR) were 80%
      and 13%, respectively. In group A, 100% had CR. Treatment failure was 7% and all
      were in group B, which was mainly due to poor compliance. A Chi-square test
      showed significant relationship between OvR and RT duration (P <0.001), and a
      positive trend between CR and fraction size of 2 Gy (P = 0.053). All acute
      toxicities were grade <= 2, specifically mucositis (48%), xerostomia (45%), skin
      erythema (41%), and altered taste (14%). Two patients (6.7%) experienced long
      term grade 1 xerostomia. CONCLUSION: RT provides a sustained long-term cosmetic
      control for BLEC of the parotid glands in HIV patients. Failures are uncommon,
      and the late side effects have been negligible.

PMID- 23532714
TI  - Enhanced vascular chymase-dependent conversion of endothelin in the diabetic
      kidney.
AB  - BACKGROUND: Diabetic nephropathy (DN) is associated with enhanced renal, plasma,
      and urinary endothelin (ET)-1 levels. Chymase cleaves Big ET-1 (1-38) to ET-1 (1
      31), which is further cleaved by neutral endopeptidase to ET-1 (1-21). The
      current study tested the hypothesis that afferent arterioles (AA) of diabetic
      kidneys exhibit enhanced vasoconstrictor responses to chymase-dependent
      intrarenal ET formation compared to control kidneys. METHODS: In situ
      juxtamedullary AA vasoconstrictor responses to the intrarenal conversion of Big
      ET-1 (1-38) to ET-1 (1-21) were performed in the absence and presence of chymase
      inhibition in type 2 diabetic db/db and control db/m mice studied under in vitro
      experimental conditions. RESULTS: AA vasoconstrictor responses to Big ET-1 (1-38)
      were significantly enhanced in diabetic compared to control kidneys. In the
      presence of chymase inhibition (JNJ-18054478), AA vasoconstrictor responses of
      diabetic kidneys to Big ET-1 (1-38) were significantly less than the responses of
      control kidneys. AA diameters decreased similarly to ET-1 (1-21) in diabetic and
      control kidneys. CONCLUSIONS: AA responses to the intrarenal conversion of Big ET
      1 (1-38) to ET-1 in the absence of chymase enzymatic activity were significantly
      reduced in kidneys of diabetic compared to control mice, while the magnitude of
      the vasoconstriction to ET-1 (1-21) was not different. These data suggest that AA
      vasoconstriction produced by the chymase-dependent pathway is significantly
      greater in diabetic compared to control kidneys. We propose that intrarenal
      chymase-dependent ET-1 production contributes to the decline in function and
      progression to end-stage renal disease in patients with type 2 diabetes.

PMID- 23532715
TI  - Retinal involvement of Paracoccioidomycosis: A Case Report.
AB  - PURPOSE: to describe the clinicopathologic features and treatment of a rare case
      of systemic paracoccidioidomycosis with choroidal and retinal involvement.
      DESIGN: retrospective interventional case report. PARTICIPANT: A 36-year-old
      young man with visual impairment in left eye with anterior uveitis and presence
      of whitish perimacular choroidal nodule, multiple underlying whitish spots and
      mid-periphery exudative retinal detachment. A primary extensive work-up for
      systemic infectious, autoimmune, neoplasic or inflammatory conditions was
      performed and high-resolution computer tomography scan demonstrated asymmetric
      parietal thickening of the trachea and bilateral diffuse multiple lobular
      opacities. Pulmonary bronchoscopy/biopsy of larynx, trachea and bronchial tube
      were also performed. Histopathological evaluation showed characteristic of
      Paracoccidioidomycosis. INTERVENTION: Patient was treated with oral sulphadiazine
      (1.5 g/day). MAIN OUTCOME MEASURES: Anterior uveitis, retinal examination,
      histopathological evaluation and primary clinical outcome were observed during
      systemic treatment. RESULTS: After 3 months of irregular treatment, choroidal
      lesions decreased in size forming atrophic scars and fibrotic spots; however
      visual acuity did not show any improvement. CONCLUSION: We report a rare case of
      systemic paracoccidioidomycosis with choroidal and retinal involvement treated
      with oral sulphadiazine.

PMID- 23532716
TI  - Optical magnification should be mandatory for microsurgery: scientific basis and
      clinical data contributing to quality assurance.
AB  - BACKGROUND: Microsurgical techniques are considered standard procedures in
      reconstructive surgery. Although microsurgery by itself is defined as surgery
      aided by optical magnification, there are no guidelines for determining in which
      clinical situations a microscope or loupe should be used. Therefore, we conducted
      standardized experiments to objectively assess the impact of optical
      magnification in microsurgery. METHODS: Sixteen participants of microsurgical
      training courses had to complete 2 sets of experiments. Each set had to be
      performed with an unaided eye, surgical loupes, and a regular operating
      microscope. The first set of experiments included coaptation of a chicken femoral
      nerve, and the second set consisted of anastomosing porcine coronary arteries.
      Evaluation of the sutured nerves and vessels were performed by 2 experienced
      microsurgeons using an operating microscope. RESULTS: The 16 participants of the
      study completed all of the experiments. The nerve coaptation and vascular
      anastomoses exercises showed a direct relationship of error frequency and lower
      optical magnification, meaning that the highest number of microsurgical errors
      occurred with the unaided eye. For nerve coaptation, there was a strong
      relationship (P<0.05) between the number of mistakes and magnification, and this
      relationship was very strong (P<0.01) for vascular anastomoses. CONCLUSIONS: We
      were able to prove that microsurgical success is directly related to optical
      magnification. The human eye's ability to discriminate potentially important
      anatomical structures is limited, which might be detrimental for clinical
      results. Although not legally mandatory, surgeries such as reparative surgery
      after hand trauma should be conducted with magnifying devices for achieving
      optimal patient outcomes.

PMID- 23532717
TI  - Conceptual frameworks and methods for advancing invasion ecology.
AB  - Invasion ecology has much advanced since its early beginnings. Nevertheless,
      explanation, prediction, and management of biological invasions remain difficult.
      We argue that progress in invasion research can be accelerated by, first,
      pointing out difficulties this field is currently facing and, second, looking for
      measures to overcome them. We see basic and applied research in invasion ecology
      confronted with difficulties arising from (A) societal issues, e.g., disparate
      perceptions of invasive species; (B) the peculiarity of the invasion process,
      e.g., its complexity and context dependency; and (C) the scientific methodology,
      e.g., imprecise hypotheses. To overcome these difficulties, we propose three key
      measures: (1) a checklist for definitions to encourage explicit definitions; (2)
      implementation of a hierarchy of hypotheses (HoH), where general hypotheses
      branch into specific and precisely testable hypotheses; and (3) platforms for
      improved communication. These measures may significantly increase conceptual
      clarity and enhance communication, thus advancing invasion ecology. 

PMID- 23532719
TI  - Pisa syndrome in Parkinson's disease: a mobile or fixed deformity?
AB  - BACKGROUND: Although Pisa syndrome and scoliosis are sometimes used
      interchangeably to describe a laterally flexed postural deviation in Parkinson's
      disease (PD), the imaging findings of Pisa syndrome in PD have not been
      previously studied in detail. METHODS: Patients with PD and Pisa syndrome
      (lateral flexion >10 degrees  in the standing position) were examined clinically
      and underwent radiological assessment using standing radiograph and supine CT
      scan of the whole spine. RESULTS: Fifteen patients were included in this
      observational study. All patients had scoliosis on standing radiographs, and 12
      had scoliosis persisting in the supine position. Scoliotic curves improved by a
      mean of 44% when patients moved from standing to supine. Only a quarter of
      patients with structural scoliosis had evidence of bony fusion on the side of
      their lateral deviation rendering their deformity fixed. CONCLUSIONS: Pisa
      syndrome describes a patient who lists to the side whereas scoliosis is defined
      by spinal curvature and rotation and may not be associated with lateral flexion.
      The finding of 'structural scoliosis' in Pisa syndrome should not preclude
      intervening to improve posture as most patients had little or no evidence of
      structural bony changes even when the deformity had been present for a number of
      years.

PMID- 23532720
TI  - Neurological picture. Trigeminal neuralgia after pontine infarction affecting the
      ipsilateral trigeminal nerve.

PMID- 23532718
TI  - A gutsy task: generating intestinal tissue from human pluripotent stem cells.
AB  - Many significant advances in our understanding of intestine development,
      intestinal stem cell homeostasis and differentiation have been made in recent
      years. These advances include novel techniques to culture primary human and mouse
      intestinal epithelium in three-dimensional matrices, and de novo generation of
      human intestinal tissue from embryonic and induced pluripotent stem cells. This
      short review will focus on the directed differentiation of human pluripotent stem
      cells into intestinal tissue, highlight novel uses of this tissue, and compare
      and contrast this system to primary intestinal epithelial cultures.

PMID- 23532721
TI  - Four-channel surface coil array for 300-MHz pulsed EPR imaging: proof-of-concept
      experiments.
AB  - Time-domain electron paramagnetic resonance imaging is currently a useful
      preclinical molecular imaging modality in experimental animals such as mice and
      is capable of quantitatively mapping hypoxia in tumor implants. The microseconds
      range relaxation times (T1 and T2) of paramagnetic tracers and the large
      bandwidths (tens of MHz) to be excited by electron paramagnetic resonance pulses
      for spatial encoding makes imaging of large objects a challenging task. The
      possibility of using multiple array coils to permit studies on large sized object
      is the purpose of the present work. Toward this end, the use of planar array
      coils in different configurations to image larger objects than cannot be fully
      covered by a single resonator element is explored. Multiple circular surface
      coils, which are arranged in a plane or at suitable angles mimicking a volume
      resonator, are used in imaging a phantom and a tumor-bearing mouse leg. The image
      was formed by combining the images collected from the individual coils with
      suitable scaling. The results support such a possibility. By multiplexing or
      interleaving the measurements from each element of such array resonators, one can
      scale up the size of the subject and at the same time reduce the radiofrequency
      power requirements and increase the sensitivity.

PMID- 23532722
TI  - Graphene quantum dot hybrids as efficient metal-free electrocatalyst for the
      oxygen reduction reaction.
AB  - The doping of heteroatoms into graphene quantum dot nanostructures provides an
      efficient way to tune the electronic structures and make more active sites for
      electro-catalysis, photovoltaic, or light emitting applications. Other than the
      modification of chemical composition, novel architecture is very desirable to
      enrich the research area and provides a wide range of choices for the diverse
      applications. Herein, we show a novel lotus seedpod surface-like pattern of zero
      dimension (0D) seed-like N-GODs of ca.3 nm embedded on the surface of a two
      dimension (2D) N-GQD sheet of ca.35 nm. It is demonstrated that different
      photoluminescence (PL) could be tuned easily, and the novel multidimensional
      structure displays excellent performance toward oxygen reduction reaction in
      alkaline solutions. Thus, the fabricated N-GQD hybrids show bright perspective in
      biomedical imaging, biosensors, and conversion and storage of energy.

PMID- 23532723
TI  - Mortality among shipbreaking workers in Taiwan--a retrospective cohort study from
      1985 to 2008.
AB  - BACKGROUND: Shipbreaking workers are typically exposed to a wide range of
      hazardous chemicals. However, long-term follow-up studies of their mortality
      patterns are lacking. This study examined mortality among shipbreaking workers
      over a 24-year follow-up period. METHODS: A total of 4,962 shipbreaking workers
      were recruited from the database of the Kaohsiung Shipbreaking Workers Union. The
      data were then linked to the Taiwan National Death Registry from 1985 to 2008.
      The mortality ratios-standardized for age and calendar years-(SMRs) for various
      causes of deaths were calculated with reference to the general population of
      Taiwan. RESULTS: Among men workers, a statistically significant increased SMR was
      observed for all causes (SMR = 1.28), all cancers (SMR = 1.26; particularly
      noteworthy for lesions of oral and nasopharyngeal: SMR 2.03, liver: SMR 4.63, and
      lung: SMR 1.36), cirrhosis of the liver (SMR = 1.32), and accidents (SMR = 1.91).
      A statistically significant increase in mortality was observed for respiratory
      system cancer (SMR = 1.87) and lung cancer (SMR = 1.91) among workers with a
      longer duration of employment (>=7 years). The result also showed that among
      shipbreaking workers who were still alive, two people had mesothelioma and 10
      people have asbestosis. CONCLUSIONS: Those employed in shipbreaking industries
      experienced an increase in mortality from all causes. The increased SMR for lung
      cancer was probably related to asbestos, metals, and welding fume exposure.

PMID- 23532726
TI  - Surgical views: thoracoscopy: basic principles, anesthetic concerns,
      instrumentation, and thoracic access.
AB  - Thoracoscopic surgery offers an exciting method for treating a variety of
      thoracic disease processes. To date, several thoracoscopic procedures have been
      described in veterinary patients. This article discusses the basic principles of
      thoracoscopic surgery and thoracic access, anesthetic concerns, and required
      instrumentation. A companion article discussing the surgical techniques of
      thoracoscopic pericardial window creation, subphrenic pericardectomy,
      thoracoscopic lung biopsy, lung lobectomy, thoracic duct ligation, and cranial
      mediastinal mass excision will be published in the February 2013 issue.

PMID- 23532725
TI  - Design of peptide affinity ligands for S-protein: a comparison of combinatorial
      and de novo design strategies.
AB  - Design of peptide affinity ligands against biological targets is important for a
      broad range of applications. Here, we report on de novo and combinatorial
      strategies for the design of high-affinity and high-specificity peptides against
      S-protein as a target. The peptide libraries employed in this study contain (1)
      consensus motif (CM) sequences identified from high-throughput phage
      combinatorial screening, (2) point mutations of CM sequences, and (3) de novo
      sequences rationally designed based on stereo-chemical information of the complex
      between S-protein and its natural ligand, S-peptide. In general, point mutations
      to CM allowed for modulating peptide affinity and specificity over a broad range.
      This is particularly useful in designing peptides with varying affinities and
      specificities for the target. De novo sequences, especially those based on the S
      protein binding pocket, on average bound with higher affinities within a narrow
      range (10-100 nM) as compared to point mutations to CM (1 nM-2 MUM). As such, the
      approaches described here serve as a general guide for optimizing the design of
      peptide affinity ligands for a wide range of target proteins or applications.

PMID- 23532727
TI  - New alternatives for minimally invasive management of uroliths: lower urinary
      tract uroliths.
AB  - In small animals, removal is indicated for lower urinary tract calculi that are
      not amenable to medical dissolution and are causing, or may cause, urinary tract
      obstruction, inflammation, or recurrent infection. Surgical removal of lower
      urinary tract uroliths by cystotomy or urethrotomy has been the traditional
      method. The current standard of care for human urinary tract stones involves the
      use of lithotripsy and is minimally invasive. This article reviews the current
      literature on the various minimally invasive options available for managing lower
      urinary tract stones in small animal veterinary patients. Options for managing
      nephroliths and ureteroliths will be presented in forthcoming companion articles.

PMID- 23532728
TI  - Dermatologic emergencies: identification and treatment.
AB  - Skin disease is one of the most common reasons dogs and cats are taken to the
      veterinarian. While many dermatologic conditions cause mild, localized signs,
      some, such as erythema multiforme, toxic epidermal necrolysis, cutaneous
      vasculitis, cutaneous drug eruptions, and thermal burns, can cause severe
      cutaneous signs and may have serious systemic consequences. These patients may
      present on an emergency basis and require intensive monitoring, diagnostics, and
      care. Lack of familiarity with these conditions may delay diagnosis and
      appropriate treatment. Pyotraumatic dermatitis may also prompt owners to seek
      emergency veterinary care due to the severe appearance of associated lesions.

PMID- 23532729
TI  - Corneal ulcers in horses.
AB  - Corneal ulceration is commonly diagnosed by equine veterinarians. A complete
      ophthalmic examination as well as fluorescein staining, corneal cytology, and
      corneal bacterial (aerobic) and fungal culture and sensitivity testing are
      necessary for all infected corneal ulcers. Appropriate topical antibiotics,
      topical atropine, and systemic NSAIDs are indicated for all corneal ulcers. If
      keratomalacia (melting) is observed, anticollagenase/antiprotease therapy, such
      as autologous serum, is indicated. If fungal infection is suspected, antifungal
      therapy is a necessity. Subpalpebral lavage systems allow convenient, frequent,
      and potentially long-term therapy. Referral corneal surgeries provide additional
      therapeutic options when the globe's integrity is threatened or when improvement
      has not been detected after appropriate therapy.

PMID- 23532730
TI  - Traumatic foot injuries in horses: surgical management.
AB  - Managing traumatic foot wounds in horses may require surgical intervention. These
      wounds include coronary-band and heel-bulb lacerations, septic pedal osteitis,
      septic navicular bursitis, sepsis of the collateral cartilages, and hoof-wall
      injuries. This article provides a practical overview of the surgical management
      of these types of wounds.

PMID- 23532731
TI  - Skin rash during cetuximab treatment in advanced colorectal cancer: is age a
      clinical predictor?
AB  - PURPOSE: The aim of this study is to evaluate the intensity and the duration of
      skin rash in young and elderly patients treated with cetuximab for advanced
      colorectal cancer, in order to define a possible relationship between age and
      skin toxicity. METHODS: We retrospectively analyzed all consecutive patients with
      advanced colorectal cancer who developed skin rash during cetuximab treatment at
      the Clinical Oncology Unit from June 2006 to May 2011. We divided the general
      case study into two subgroups: young and elderly patients (>= 65 years old), and
      we compared clinical, pathological, and therapeutical characteristics of both
      subgroups. RESULTS: Among the 31 patients affected by advanced colorectal cancer
      (64.5 % with colon cancer and 35.5 % with rectal cancer) treated with cetuximab,
      19 patients (61.3 %) developed skin toxicities: seven patients (36.8 %) had grade
      1 skin rash, nine patients (47.4 %) had grade 2, three patients (15.8 %) had
      grade 3, and no grade 4 was found. Ten (52.6 %) out of 19 patients were elderly
      (>65 years). Concerning skin rash, grading was substantially comparable between
      the two subgroups, but median duration of skin rash was higher in the first
      subgroup for all grades. The univariate analysis showed no statistical
      significant difference in overall survival between young and elderly patients (p
      = 0.171), such as age that does not seem to statistically influence the
      appearance (p = 0.386), duration (p = 0.455), and grade of skin rash (p = 0.765).
      CONCLUSIONS: Age is an insufficient predictor of skin toxicity during cetuximab
      treatment in advanced colorectal cancer and does not seem to statistically
      influence the appearance, duration, and grade of skin rash.

PMID- 23532732
TI  - MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor
      resistance: rationale to combine romidepsin with an MEK inhibitor.
AB  - To identify molecular determinants of histone deacetylase inhibitor (HDI)
      resistance, we selected HuT78 cutaneous T-cell lymphoma (CTCL) cells with
      romidepsin in the presence of P-glycoprotein inhibitors to prevent transporter
      upregulation. Resistant sublines were 250- to 385-fold resistant to romidepsin
      and were resistant to apoptosis induced by apicidin, entinostat, panobinostat,
      belinostat, and vorinostat. A custom TaqMan array identified increased insulin
      receptor (INSR) gene expression; immunoblot analysis confirmed increased protein
      expression and a four- to eightfold increase in mitogen-activated protein kinase
      (MAPK) kinase (MEK) phosphorylation in resistant cells compared with parental
      cells. Resistant cells were exquisitely sensitive to MEK inhibitors, and
      apoptosis correlated with restoration of proapoptotic Bim. Romidepsin combined
      with MEK inhibitors yielded greater apoptosis in cells expressing mutant KRAS
      compared with romidepsin treatment alone. Gene expression analysis of samples
      obtained from patients with CTCL enrolled on the NCI1312 phase 2 study of
      romidepsin in T-cell lymphoma suggested perturbation of the MAPK pathway by
      romidepsin. Immunohistochemical analysis of Bim expression demonstrated decreased
      expression in some skin biopsies at disease progression. These findings implicate
      increased activation of MEK and decreased Bim expression as a resistance
      mechanism to HDIs, supporting combination of romidepsin with MEK inhibitors in
      clinical trials.

PMID- 23532733
TI  - SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition
      of cathepsin G.
AB  - Bone marrow (BM) holds a large reserve of polymorphonuclear neutrophils (PMNs)
      that are rapidly mobilized to the circulation and tissues in response to danger
      signals. SerpinB1 is a potent inhibitor of neutrophil serine proteases neutrophil
      elastase (NE) and cathepsin G (CG). SerpinB1 deficiency (sB1(-/-)) results in a
      severe reduction of the BM PMN reserve and failure to clear bacterial infection.
      Using BM chimera, we found that serpinB1 deficiency in BM cells was necessary and
      sufficient to reproduce the BM neutropenia of sB1(-/-) mice. Moreover, we showed
      that genetic deletion of CG, but not NE, fully rescued the BM neutropenia in sB1(
      /-) mice. In mixed BM chimera and in vitro survival studies, we showed that CG
      modulates sB1(-/-) PMN survival through a cell-intrinsic pathway. In addition,
      membrane permeabilization by lysosomotropic agent l-leucyl-l-leucine methyl ester
      that allows cytosolic release of granule contents was sufficient to induce rapid
      PMN death through a CG-dependent pathway. CG-mediated PMN cytotoxicity was only
      partly blocked by caspase inhibition, suggesting that CG cleaves a distinct set
      of targets during apoptosis. In conclusion, we have unveiled a new cytotoxic
      function for the serine protease CG and showed that serpinB1 is critical for
      maintaining PMN survival by antagonizing intracellular CG activity.

PMID- 23532734
TI  - Endothelial cells require miR-214 to secrete exosomes that suppress senescence
      and induce angiogenesis in human and mouse endothelial cells.
AB  - Signaling between endothelial cells, endothelial progenitor cells, and stromal
      cells is crucial for the establishment and maintenance of vascular integrity and
      involves exosomes, among other signaling pathways. Exosomes are important
      mediators of intercellular communication in immune signaling, tumor survival,
      stress responses, and angiogenesis. The ability of exosomes to incorporate and
      transfer messenger RNAs (mRNAs) encoding for "acquired" proteins or micro RNAs
      (miRNAs) repressing "resident" mRNA translation suggests that they can influence
      the physiological behavior of recipient cells. We demonstrate that miR-214, an
      miRNA that controls endothelial cell function and angiogenesis, plays a dominant
      role in exosome-mediated signaling between endothelial cells. Endothelial cell
      derived exosomes stimulated migration and angiogenesis in recipient cells,
      whereas exosomes from miR-214-depleted endothelial cells failed to stimulate
      these processes. Exosomes containing miR-214 repressed the expression of ataxia
      telangiectasia mutated in recipient cells, thereby preventing senescence and
      allowing blood vessel formation. Concordantly, specific reduction of miR-214
      content in exosome-producing endothelial cells abolishes the angiogenesis
      stimulatory function of the resulting exosomes. Collectively, our data indicate
      that endothelial cells release miR-214-containing exosomes to stimulate
      angiogenesis through the silencing of ataxia telangiectasia mutated in
      neighboring target cells.

PMID- 23532735
TI  - MYD88 L265P mutation in Waldenstrom macroglobulinemia.
AB  - Mutation of the MYD88 gene has recently been identified in activated B-cell-like
      diffuse cell lymphoma and enhanced Janus kinase/signal transducer and activator
      of transcription (JAK-STAT) and nuclear factor kappaB (NF-kappaB) signaling
      pathways. A whole exome-sequencing study of Waldenstrom macroglobulinemia (WM)
      suggested a high frequency of MYD88 L265P mutation in WM. The genetic background
      is not fully deciphered in WM, although the role of NF-kappaB and JAK-STAT has
      been demonstrated. We analyzed MYD88 mutation in exon 5 and characterized the
      clinical significance of this genetic alteration in 67 WM patients. Clinical
      features; immunophenotypic markers; and conventional cytogenetic, fluorescence in
      situ hybridization, and single nucleotide polymorphism array data were analyzed.
      MYD88 L265P mutation was acquired in 79% of patients. Overall, we have identified
      alteration of the MYD88 locus in 91% of WM patients, including 12% with gain on
      chromosome 3 at the 3p22 locus that included the MYD88 gene. Patients with
      absence of MYD88 mutation were WM characterized with a female predominance, a
      splenomegaly, gain of chromosome 3, and CD27 expression. Importantly, inhibition
      of MYD88 signaling induced cytotoxicity and inhibited cell growth of cell lines
      issued from patients with WM. In conclusion, these results confirm a high
      frequency of MYD88 L265P mutation in WM. The discovery of MYD88 L265P mutation
      may contribute to a better understanding of the physiopathogeny of WM.

PMID- 23532736
TI  - Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice
      through a Foxp3-independent mechanism that relies on IL-10.
AB  - Current treatment of hemophilia consists of the administration of recombinant
      clotting factors, such as factor VIII (FVIII). However, patients with severe
      hemophilia can mount immune responses targeting therapeutically administered
      FVIII through inhibitory immunoglobulins that limit treatment efficacy. Induction
      of immune tolerance to FVIII in hemophilia has been extensively studied but
      remains an unmet need. We found that nondepleting anti-CD4 monoclonal antibodies
      (mAbs) are effective in inducing long-term tolerance to FVIII in different
      strains of hemophilic mice. Tolerance induction was facilitated when anti-CD4
      mAbs were administered together with FVIII adsorbed in an adjuvant (alum). The
      observed state of tolerance was antigen specific, with mice remaining immune
      competent to respond to different antigens. Importantly, we found that following
      immunization with FVIII, the primed cells remained susceptible to tolerance
      induction. Studies with Foxp3-deficient and interleukin 10 (IL-10)-deficient mice
      demonstrated that the underlying tolerance mechanism is Foxp3 independent but
      requires IL-10. Our data show that an adjuvant, when administered together with a
      tolerizing agent such as nondepleting anti-CD4, can facilitate the induction of
      long-term tolerance to recombinant proteins, possibly not only in hemophilia but
      also in other diseases that are treated with potentially immunogenic
      therapeutics.

PMID- 23532737
TI  - Clinical and economic characteristics of hip fracture patients with and without
      muscle atrophy/weakness in the United States.
AB  - This retrospective analysis of hip fracture patients with and without muscle
      atrophy/weakness (MAW) revealed that those with MAW had significantly higher
      healthcare utilization and costs compared with hip fracture patients without MAW.
      PURPOSE: Examine the demographics, clinical characteristics, and healthcare
      resource utilization and costs of hip fracture patients with and without MAW.
      METHODS: Using a large US claims database, individuals who were newly
      hospitalized for hip fracture between 1 Jan 2006 and 30 September 2009 were
      identified. Patients aged 50-64 years with commercial insurance (Commercial) or
      65+ years with Medicare supplemental insurance (Medicare) were included. The
      first hospitalization for hip fracture was defined as the index stay. Patients
      were categorized into three cohorts: patients with medical claims associated with
      MAW over the 12 months before the index stay (pre-MAW), patients whose first MAW
      claim occurred during or over the 12 months after the index stay (post-MAW), and
      patients without any MAW claim (no-MAW). Multivariate regressions were performed
      to assess the association between MAW and healthcare costs over the 12-month post
      index period, as well as the probability of re-hospitalization. RESULTS: There
      were 26,122 Medicare (pre-MAW, 839; post-MAW, 2,761; no-MAW, 22,522) and 5,100
      Commercial (pre-MAW, 132; post-MAW, 394; no-MAW, 4,574) hip fracture patients
      included in this study. Controlling for cross-cohort differences, both the pre
      MAW and post-MAW cohorts had significantly higher total healthcare costs
      (Medicare, $7,308 and $18,753 higher; Commercial, $18,679 and $25,495 higher)
      than the no-MAW cohort (all p < 0.05) over the 12-month post-index period. The
      post-MAW cohort in both populations was also more likely to have any all-cause or
      fracture-related re-hospitalization during the 12-month post-index period.
      CONCLUSIONS: Among US patients with hip fractures, those with MAW had higher
      healthcare utilization and costs than patients without MAW.

PMID- 23532738
TI  - Androgen deprivation and androgen receptor competition by bicalutamide induce
      autophagy of hormone-resistant prostate cancer cells and confer resistance to
      apoptosis.
AB  - BACKGROUND: Treatment of advanced prostate cancer (PCa) relies on pharmacological
      or surgical androgen deprivation. However, it is only temporarily efficient.
      After a few months or years, the tumor relapses despite the absence of androgenic
      stimulation: a state referred to as hormone-refractory prostate cancer (HRPCa).
      Although autophagy confers chemoresistance in some cancers, its role in the
      development of HRPCa remains unknown. METHODS: Autophagic flux was assayed by GFP
      LC3 clustering, by LC3-I to LC3-II conversion and transmission electron
      microscopy. Cell death was detected by sub-G1 quantification and concomitant
      measurement of transmembrane mitochondrial potential and plasma membrane
      permeabilization. Inhibition of autophagy was achieved by siRNAs and
      pharmacological inhibitors. RESULTS: Androgen deprivation or treatment with the
      anti-androgen bicalutamide promoted autophagy in HRPCa-derived LNCaP cells. This
      effect was dramatically reduced after depletion of Atg5 and Beclin-1, two
      canonical autophagy genes, and was associated with an inhibition of the androgen
      induced mTOR pathway. The depletion of Atg5 and Beclin-1 significantly increased
      the level of cell death induced by androgen deprivation or bicalutamide. Finally,
      the safe anti-malarial drug chloroquine, an inhibitor of autophagy, dramatically
      increased cell death after androgen deprivation or bicalutamide treatment.
      CONCLUSION: Taken together, our data suggest that autophagy is a protective
      mechanism against androgen deprivation in HRPCa cells and that chloroquine could
      restore hormone dependence. This set of data could lead to the development of new
      therapeutic strategy against HRPCa.

PMID- 23532739
TI  - G-protein-coupled receptor kinase 2 and hypertension: molecular insights and
      pathophysiological mechanisms.
AB  - Numerous factors partake in the fine-tuning of arterial blood pressure. The
      heptahelical G-protein-coupled receptors (GPCRs) represent one of the largest
      classes of cell-surface receptors. Further, ligands directed at GPCRs account for
      nearly 30 % of current clinical pharmaceutical agents available. Given the wide
      variety of GPCRs involved in blood pressure control, it is reasonable to
      speculate for a potential role of established intermediaries involved in the GPCR
      desensitization process, like the G-protein-coupled receptor kinases (GRKs), in
      the regulation of vascular tone. Of the seven mammalian GRKs, GRK2 seems to be
      the most relevant isoform at the cardiovascular level. This review attempts to
      assemble the currently available information concerning GRK2 and hypertension,
      opening new potential fields of translational investigation to treat this vexing
      disease.

PMID- 23532740
TI  - The importance of 24-hour ambulatory blood pressure monitoring in patients at
      risk of cardiovascular events.
AB  - The accuracy of clinic blood pressure (BP) measurements is limited due to the
      presence of 24-hour BP variability and white-coat or masked hypertension. In
      contrast, 24-hour ambulatory BP monitoring (ABPM) has evolved into an accurate
      and reproducible tool for the assessment and management of hypertension. Various
      out-of-office measurements can be obtained using ABPM data, including morning,
      daytime, night-time and average 24-hour BP. Thus, in clinical practice, ABPM can
      be used to identify masked hypertension or excessive BP reduction. Furthermore,
      ABPM data can identify early-morning hypertension and excessive BP variability,
      both of which correlate with target-organ damage and cardiovascular outcomes. In
      large outcomes trials, ABPM sub-studies are increasingly performed to help
      further understand patient outcomes. However, it is evident that control of BP
      over the full 24-hour period, particularly during the risky early morning period,
      is not being achieved in general practice. In clinical trials of antihypertensive
      efficacy, a useful calculation is the smoothness index. This measure assesses the
      degree of 24-hour BP reduction, as well as its distribution pattern, throughout
      the 24-hour period. Importantly, the index correlates with hypertension
      associated target organ damage, unlike the commonly used trough to peak ratio.
      Smooth BP control according to this index is achieved with long-acting drugs,
      such as telmisartan or amlodipine, which provide smooth 24-hour BP control, even
      during the early morning period. In summary, the use of ABPM is expanding, both
      in clinical practice and in trials, as it provides a closer correlation to
      prognosis than clinic BP measures. When choosing an antihypertensive agent for
      patients with hypertension, it is important to consider reducing BP variability
      by using longer acting antihypertensives, which may help to prevent
      cardiovascular morbidity and mortality.

PMID- 23532741
TI  - Infusion of bevacizumab increases the risk of intestinal perforation: results on
      a series of 143 patients consecutively treated.
AB  - Bevacizumab is largely used in colorectal cancer patients. Postsurgical healing
      complications have been described for patients following treatment with
      Bevacizumab. We report three cases of spontaneous intestinal perforation
      following infusion of Bevacizumab. From January 2002 through October 2010,
      Bevacizumab was delivered in 143 patients. Spontaneous intestinal perforation
      occurred in 3 cases (2.1 %). Bevacizumab may result in severe complications.
      Therefore, it is important to consider every patient treated with Bevacizumab at
      risk for life-threatening gastro-intestinal complications.

PMID- 23532742
TI  - Organization of work in the agricultural, forestry, and fishing sector in the US
      southeast: implications for immigrant workers' occupational safety and health.
AB  - BACKGROUND: There is widespread agreement that work organization is an important
      element of occupational safety and health, but the health effects of many aspects
      of work organization are likely to vary considerably across different sectors of
      work and geographies. METHODS: We examined existing employment policies and work
      organization-related research relevant specifically to immigrant workers in the
      Agriculture, Forestry, and Fishing (AgFF) Sector of the US workforce focusing,
      when possible, on the southeastern US. RESULTS: A number of specific aspects of
      work organization within AgFF subsectors have been described, but most of this
      literature exists outside the purview of occupational health. There are few
      studies that directly examine how attributes of work organization relevant to the
      AgFF Sector affect workers', much less immigrant workers', occupational health
      exposures and outcomes. CONCLUSIONS: In contrast to the broader literature,
      research linking occupational health outcomes to work organization in the AgFF
      Sector is limited and weak. A systematic program of research and intervention is
      needed to develop strategies that eliminate or substantially mitigate the
      deleterious health effects of occupational exposures whose origins likely lie in
      the organization of AgFF work.

PMID- 23532743
TI  - A structural equation modelling approach to explore the role of B vitamins and
      immune markers in lung cancer risk.
AB  - The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity
      and regulating gene expression, and may be involved in the process of
      carcinogenesis. Several B-vitamins and amino acids have been implicated in lung
      cancer risk, via the OCM directly as well as immune system activation. However it
      is unclear whether these factors act independently or through complex mechanisms.
      The current study applies structural equations modelling (SEM) to further
      disentangle the mechanisms involved in lung carcinogenesis. SEM allows
      simultaneous estimation of linear relations where a variable can be the outcome
      in one equation and the predictor in another, as well as allowing estimation
      using latent variables (factors estimated by correlation matrix). A large number
      of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls
      nested within the European Prospective Investigation into Cancer and Nutrition
      (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated
      in relation to lung cancer risk: methionine-homocysteine metabolism, folate
      cycle, transsulfuration, and mechanisms involved in inflammation and immune
      activation, all adjusted for tobacco exposure. The hypothesized SEM model
      confirmed a direct and protective effect for factors representing methionine
      homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an
      indirect protective effect of folate cycle (p = 0.019), after adjustment for
      tobacco smoking. In conclusion, our results show that in the investigation of the
      involvement of the OCM, the folate cycle and immune system in lung
      carcinogenesis, it is important to consider complex pathways (by applying SEM)
      rather than the effects of single vitamins or nutrients (e.g. using traditional
      multiple regression). In our study SEM were able to suggest a greater role of the
      methionine-homocysteine metabolism and immune activation over other potential
      mechanisms. 

PMID- 23532744
TI  - Midlife cardiovascular risk factors and late cognitive impairment.
AB  - Cardiovascular risk factors increase the risk of dementia in later life. The aims
      of the current study were to assess the effect of multiple midlife cardiovascular
      risk factors on the risk of cognitive impairment in later life, and to assess the
      validity of the previously suggested CAIDE Study risk score predicting dementia
      risk 20 years later. A total of 2,165 Finnish twins were followed and at the end
      of the follow-up their cognitive status was assessed with a validated telephone
      interview. The assessment of the risk factors at baseline was based on a self
      report questionnaire. Relative risk ratios (RR) were calculated and receiver
      operating characteristic analyses performed. Midlife obesity (RR 2.42, 95 % CI
      1.47-3.98), hypertension (RR 1.38, 95 % CI 1.01-1.88) and low leisure time
      physical activity (RR 2.52, 95 % CI 1.10-5.76) increased the risk of cognitive
      impairment after a mean follow-up of 22.6 +/- 2.3 years. Hypercholesterolemia did
      not significantly increase the risk (RR 1.52, 95 % CI 0.92-2.51). Overweight
      individuals who gained more than 10 % weight between 1981 and 1990 had an
      increased risk of cognitive impairment (RR 4.27, 95 % CI 1.62-11.2). The CAIDE
      Study risk score combining various individual risk factors had an area-under
      curve of 0.74 (95 % CI 0.69-0.79, n = 591), and there was a strong association
      between an increasing risk score and the risk of cognitive impairment. The
      results indicate that multiple midlife cardiovascular risk factors increase the
      risk of cognitive impairment in later life. Also, a risk score including easily
      measurable midlife factors predicts an individual's cognitive impairment risk
      well.

PMID- 23532745
TI  - Healthy lifestyle behaviors and decreased risk of mortality in a large
      prospective study of U.S. women and men.
AB  - Adiposity, insufficient physical activity, cigarette smoking, and poor diet have
      all been related independently to increased chronic disease risk, but their joint
      impact on overall health remains unclear. In a cohort of 170,672 women and men
      aged 51-71 years at baseline in 1996/1997 and followed-up through 2009, we
      investigated the individual and joint impact of four low-risk lifestyle factors:
      abdominal leanness (waist circumference <88 cm in women and <102 cm in men);
      recommended physical activity level (30 min or more of moderate exercise at least
      5 times per week or 20 min or more of vigorous exercise at least 3 times per
      week); long-term non-smoking (never-smoker or quit smoking more than 10 years
      ago); and healthy diet (Mediterranean diet score within the upper two sex
      specific quintiles). During 2,126,089 person-years of follow-up, 20,903
      participants died. In multivariate Cox models, statistically significant
      decreased risks of mortality were observed for the low-risk factors abdominal
      leanness (relative risk (RR) = 0.86; 95 % confidence interval (CI) = 0.83-0.89),
      physical activity (RR = 0.86; 95 % CI = 0.84-0.89), non-smoking (RR = 0.43; 95 %
      CI = 0.42-0.45), and healthy diet (RR = 0.86; 95 % CI = 0.83-0.88). The larger
      the number of low-risk lifestyle factors, the lower was the mortality risk. The
      RR comparing adherence to all versus none of the factors was 0.27 (95 % CI = 0.25
      0.29). We estimate that 33 % (95 % CI = 30-35 %) of deaths in our cohort were
      premature and could have been avoided if all study participants had adhered to
      all low-risk factors.

PMID- 23532746
TI  - Randomized controlled study of the T-type calcium channel antagonist MK-8998 for
      the treatment of acute psychosis in patients with schizophrenia.
AB  - OBJECTIVE: This study aimed to evaluate whether the T-type calcium channel
      antagonist MK-8998 was effective in treating acute psychosis in patients with
      schizophrenia. METHODS: This was a randomized, double-blind, parallel-group
      study. After a placebo lead-in, acutely psychotic inpatients with schizophrenia
      were randomized to 4 weeks of MK-8998 12/16 mg daily (N = 86), olanzapine 10/15
      mg daily (N = 47), or placebo (N = 83). The primary efficacy measure was score on
      the Positive and Negative Syndrome Scale (PANSS). RESULTS: Out of 216 randomized
      patients, 158 completed the 4-week study: MK-8998 = 58 (67.4%), olanzapine = 38
      (80.9%), and placebo = 62 (74.7%). The mean changes from baseline in PANSS score
      at week 4 for MK-8998 and olanzapine were not significantly different from
      placebo: MK-8998-placebo difference = -0.6 [95% confidence interval (CI): -7.0,
      5.8], p = 0.9; olanzapine-placebo difference = -4.3 [95% CI: -11.7, 3.1), p =
      0.3. A responder rate analysis (>=20% improvement from baseline in PANSS score)
      suggested an advantage of olanzapine over placebo (odds ratio = 2.20 [95% CI:
      0.95, 5.09], p = 0.07) but no effect of MK-8998 over placebo (odds ratio = 1.28
      [95% CI: 0.62, 2.64], p = 0.5). Treatments were generally well tolerated, but
      more patients reported adverse events for MK-8998 (47.7%) and olanzapine (48.9%)
      than placebo (37.3%). CONCLUSIONS: MK-8998 was not effective in treating acutely
      psychotic inpatients with schizophrenia, as measured by PANSS score at week 4.
      Because of the limited efficacy of the active comparator, we cannot exclude the
      possibility that T-type calcium channel antagonists could prove to be effective
      in schizophrenia.

PMID- 23532747
TI  - Efficacy of the novel antidepressant agomelatine for anxiety symptoms in major
      depression.
AB  - OBJECTIVES: Anxiety in major depression is associated with increased morbidity.
      The antidepressant, agomelatine, which acts as an agonist at melatonin MT(1) and
      MT(2) receptors and as an antagonist at serotonin 5-HT(2C) receptors, has
      demonstrated efficacy and safety in both major depression and generalized anxiety
      disorder. Here, we investigated the efficacy of agomelatine in anxious
      depression. METHODS: Data from three placebo-controlled short-term trials of
      agomelatine and three comparative studies of agomelatine versus fluoxetine,
      sertraline, and venlafaxine were pooled. Effects of agomelatine on anxiety
      symptoms were assessed with the Hamilton Anxiety Rating Scale in four studies
      (one vs placebo and three vs active comparator) and with the Hamilton Depression
      Rating Scale (HAMD) anxiety subscore in all six studies. Anxiolytic and
      antidepressant efficacies of agomelatine were assessed in patients with more
      severe anxiety symptoms at baseline (score >=5 on HAMD anxiety subscore).
      RESULTS: Agomelatine had a significantly greater effect on anxiety symptoms than
      both placebo and a number of comparator antidepressants. In more anxious
      depressed patients, agomelatine had a significantly greater effect on anxiety and
      depressive symptoms than both placebo and comparator antidepressants. CONCLUSION:
      Once-a-day oral agomelatine is a new, efficacious alternative option for the
      treatment of anxiety in patients with major depression.

PMID- 23532748
TI  - Levels of TNF-alpha, soluble TNF receptors (sTNFR1, sTNFR2), and cognition in
      bipolar disorder.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) may play an important role in
      bipolar disorder (BD) pathogenesis. There is only one study about a relationship
      between TNF-alpha levels and cognitive impairments in BD. The aim of the present
      study was to see whether TNF-alpha, soluble P55 TNF receptor (sTNFR1), and
      soluble P75 TNF receptor (sTNFR2) levels in BD patients are different from
      controls and to investigate the relationships between the levels of TNF-alpha,
      sTNFR1, and sTNFR2 and the cognitive functions in euthymic BD patients and
      controls. METHODS: We assessed 54 BD type I patients and 18 controls by using a
      battery of neuropsychological tests. Serum TNF-alpha levels were measured using a
      commercially available enzyme-linked immunosorbent assay, whereas serum sTNFR1
      and sTNFR2 levels were measured using a commercially enzyme-amplified sensitivity
      immunoassay kit. RESULTS: We found that levels of sTNFR1 and sTNFR2 in BD
      patients were different from controls. No difference was detected between the BD
      group and the control group for levels of TNF-alpha. TNF-alpha level was found to
      have a negative correlation with the delayed recall in RAVLT. CONCLUSIONS: High
      levels of sTNFR1 and sTNFR2 in euthymic patients showed that it may support that
      proinflammatory process continues in euthymic period. This is the first study
      which showed increased sTNFR2 levels in euthymic period, which could be
      interpreted as a compensatory mechanism and again the first which deals with
      verbal memory.

PMID- 23532749
TI  - Inferring about individual drug and schizotypy effects on cognitive functioning
      in polydrug using mephedrone users before and after clubbing.
AB  - OBJECTIVE: Mephedrone has been recently made illegal in Europe, but little
      empirical evidence is available on its impact on human cognitive functions. We
      investigated acute and chronic effects of mephedrone consumption on drug
      sensitive cognitive measures, while also accounting for the influence of
      associated additional drug use and personality features. METHOD: Twenty-six
      volunteers from the general population performed tasks measuring verbal learning,
      verbal fluency and cognitive flexibility before and after a potential drug-taking
      situation (pre-clubbing and post-clubbing at dance clubs, respectively).
      Participants also provided information on chronic and recent drug use,
      schizotypal (Oxford-Liverpool Inventory of Feelings and Experiences) and
      depressive symptoms (Beck Depression Inventory), sleep pattern and premorbid IQ.
      RESULTS: We found that (i) mephedrone users performed worse than non-users pre
      clubbing and deteriorated from the pre-clubbing to the post-clubbing assessment;
      (ii) pre-clubbing cannabis and amphetamine (not mephedrone) use predicted
      relative cognitive attenuations; (iii) post-clubbing, depression scores predicted
      relative cognitive attenuations; and (iv) schizotypy was largely unrelated to
      cognitive functioning, apart from a negative relationship between cognitive
      disorganisation and verbal fluency. CONCLUSION: Results suggest that polydrug use
      and depressive symptoms in the general population negatively affect cognition.
      For schizotypy, only elevated cognitive disorganisation showed potential links to
      a pathological cognitive profile previously reported along the psychosis
      dimension.

PMID- 23532750
TI  - Movement disorders in patients with schizophrenia and a history of substance
      abuse.
AB  - OBJECTIVE: The movement disorders acute dystonia, akathisia, Parkinsonian
      symptoms and tardive dyskinesia [extrapyramidal side effects (EPSs)] are
      recognized adverse effects of antipsychotic medication. Previous studies have
      indicated that substance abuse in patients with schizophrenia can worsen EPS.
      This study therefore investigated the relationship between drug and alcohol use
      and EPS in a group of patients with schizophrenia. METHODS: Seventy patients with
      schizophrenia assessed for drug and alcohol use, global functioning, EPS and
      suicidality. Chlorpromazine equivalents were correlated to levels of EPS and
      substance abuse. RESULTS: Current EPS were found in 65% of the sample despite
      three-quarters of the patients receiving second-generation antipsychotics. An
      even higher level of patients, 87%, was found to have a history of EPS. A long
      history of schizophrenia independently predicted presence of any EPS,
      particularly akathisia, controlling for history of substance abuse which was a
      non-significant predictor. CONCLUSIONS: History or current use of alcohol or drug
      abuse did not predict EPS, except for alcohol abuse at the time of diagnosis
      which was associated with current akathisia. Length of illness was correlated
      with EPS, whereas suicidality was not linked to akathisia. Neither chlorpromazine
      equivalent antipsychotic dose nor whether the patient received first-generation
      or second-generation antipsychotic medication was significantly associated with
      EPS or substance abuse.

PMID- 23532751
TI  - Plasma catecholamine metabolite levels and the activities of psychiatric symptoms
      in systemic lupus erythematosus.
AB  - OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is accompanied
      by neurological or psychiatric symptoms that can be severe. We hypothesized
      plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels
      were the biological marker that reflected the severity of the NPSLE psychiatric
      symptoms, and we examined MHPG and HVA levels in systemic lupus erythematosus
      (SLE) patients. METHODS: The participants were 42 healthy volunteers and 41 SLE
      patients. SLE patients were divided into the three groups: NPSLE with psychiatric
      symptoms (NP group), NPSLE without psychiatric symptoms (NN group), and SLE
      without neuropsychiatric symptoms (S group). All blood samples were drawn before
      (T0) and after 4 weeks of treatment (T4) in all SLE patients, and once in the
      healthy volunteers. Plasma levels of MHPG and HVA were analyzed using high
      performance liquid chromatography. RESULTS: Plasma MHPG levels at T0 were
      significantly increased in the SLE compared to those in healthy volunteers. The
      NN group had the greatest increase compared with other SLE patient groups. There
      were no significant differences in plasma HVA levels at T0 between the four
      groups, and there was also no difference in MHPG and HVA plasma levels between T0
      and T4. CONCLUSION: Hyperactivity of noradrenergic neurons and/or sympathetic
      nerves might be involved in SLE pathophysiology.

PMID- 23532753
TI  - Self-powered UV photosensor based on PEDOT:PSS/ZnO micro/nanowire with strain
      modulated photoresponse.
AB  - Developing tailored micro/nanostructure interfaces is an effective way to make
      novel optoelectronic devices or enhance their performances. Here we report the
      fabrication of a PEDOT:PSS/ZnO micro/nanowire-based self-powered UV photosensor.
      The generation of photocurrent at zero bias is attributed to the separation of
      photogenerated electron-hole pairs within the built-in electric field at the
      PEDOT:PSS/ZnO interface upon UV light illumination. Furthermore, the piezotronic
      effect on the UV photoresponsivity under different strains is investigated, which
      is due to the modification of energy band diagram at the p-n heterojunction by
      strain-induced piezoelectric polarization. This study demonstrates a prospective
      approach to engineering the performance of a photodetector through straining and
      may offer theoretical supporting in future optoelectronic device fabrication and
      modification.

PMID- 23532754
TI  - Candida albicans and non-C. albicans Candida species: comparison of biofilm
      production and metabolic activity in biofilms, and putative virulence properties
      of isolates from hospital environments and infections.
AB  - Candida albicans and, more recently, non-C. albicans Candida spp. are considered
      the most frequent fungi in hospitals. This study analyzed Candida spp. isolates
      and compared the frequency of different species, that is, C. albicans and non-C.
      albicans Candida spp., and the origins of isolates, that is, from hospital
      environments or infections. Yeast virulence factors were evaluated based on
      biofilm production and metabolic activity. Hemolysin production and the
      antifungal susceptibility profiles of isolates were also evaluated. Candida spp.
      were highly prevalent in samples collected from hospital environments, which may
      provide a reservoir for continuous infections with these yeasts. There were no
      differences in the biofilm productivity levels and metabolic activities of the
      environmental and clinical isolates, although the metabolic activities of non-C.
      albicans Candida spp. biofilms were greater than those of the C. albicans
      biofilms (p < 0.05). Clinical samples had higher hemolysin production (p < 0.05)
      and lower susceptibility to fluconazole (p < 0.05). Non-C. albicans Candida spp.
      predominated in samples collected from hospital environments and infections (p <
      0.05). These species had a lower susceptibility to fluconazole and amphotericin
      B, and their biofilms had higher metabolic activities than those produced by C.
      albicans, which may explain the increased incidence of fungal infections with
      these yeasts during recent years.

PMID- 23532756
TI  - c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B
      virus in human hepatoma cells.
AB  - MicroRNAs (miRNAs) regulate post-transcriptional gene expression in various
      physiological and pathological processes, including viral infections. The miR-17
      92 cluster encodes six miRNAs (miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, and
      miR-92a-1) which are transactivated by c-Myc. Because hepatitis B virus
      transactivates c-Myc, the interaction between the miR-17-92 cluster and HBV
      replication was examined in this study. Inducing HBV replication in a human
      hepatoma cell line increased miR-17-5p, miR-20a and miR-92a-1 expression. HBV
      induced overexpression of miR-17-92 was reversed by c-Myc knockdown. Antisense
      peptide nucleic acids against miR-20a and miR-92a-1 augmented HBV replication. A
      computational analysis yielded potential binding sites for miR-20a and miR-92a-1
      in the HBV genome. The direct interaction between these two miRNAs and target
      regions in HBV transcripts was confirmed by luciferase reporter analysis. These
      results demonstrated negative feedback suppression of HBV replication by the miR
      17-92 polycistron.

PMID- 23532757
TI  - Canine prostatic carcinoma.
AB  - Canine prostatic carcinoma is locally aggressive with a high rate of metastasis.
      Common metastatic sites include lymph nodes, lungs, liver, spleen, and bone.
      Staging relies on chest radiography, abdominal radiography, and abdominal
      ultrasonography, in addition to radiography of any painful regions. An enlarged,
      mineralized prostate is a frequent finding; in a castrated male dog, it is
      predictive of prostatic carcinoma. NSAIDs are an important component of
      treatment, although additional local and systemic therapies should be considered
      to improve the quality of life of these patients.

PMID- 23532758
TI  - Applied dermatology: sebaceous adenitis in dogs.
AB  - Sebaceous adenitis is an inflammatory skin disease of unknown etiology that leads
      to a poor haircoat. It occurs mostly in young adult to middle-aged dogs. Clinical
      signs vary in severity and distribution among breeds and types of haircoat.
      Lesions include alopecia, scaling, and follicular casts that are typically
      distributed over the face, head, pinnae, and trunk. Diagnosis is based on
      histopathologic findings of sebaceous gland inflammation and loss. Treatment for
      sebaceous adenitis involves lifelong management with various topical therapies
      containing keratolytic/keratoplastic agents, emollients, and humectants in
      addition to oral therapies such as omega-3/omega-6 fatty acids, cyclosporine,
      and/or retinoids.

PMID- 23532759
TI  - Focus on nutrition: the role of iodine in nutrition and metabolism.
AB  - Iodine, which forms part of thyroid hormone, is essential for sustaining life in
      vertebrate animals. An absolute iodine requirement is difficult to determine
      because of adaptive responses to varying iodine intake. Excess or deficient
      iodine intake may result in altered thyroid metabolism. The magnitude and
      direction of the response to changes in dietary intake may also depend on
      previous iodine intake. Therefore, an understanding of the distribution,
      absorption, and metabolic fate of iodine is integral to the investigation of the
      role of iodine in disease states.

PMID- 23532760
TI  - Case report: squamous cell carcinoma of the urinary bladder in a horse.
AB  - A 14-year-old Hanoverian gelding was evaluated after a 10-week history of
      occasional straining during urination and dark red urine production after
      exercise. Physical examination findings were within normal limits. After 2 weeks
      of clinical signs, ultrasonography had found no abnormalities in the kidneys or
      bladder. A freely voided urine sample revealed an elevated protein concentration
      (500 mg/dL; reference range: <100 mg/dL) and few red blood cells. Vitamin C
      supplementation was suggested to acidify the urine, as was provision of a salt
      block to encourage water intake.

PMID- 23532761
TI  - The influence of demography and local mating environment on sex ratios in a wind
      pollinated dioecious plant.
AB  - Negative frequency-dependent selection should result in equal sex ratios in large
      populations of dioecious flowering plants, but deviations from equality are
      commonly reported. A variety of ecological and genetic factors can explain biased
      sex ratios, although the mechanisms involved are not well understood. Most
      dioecious species are long-lived and/or clonal complicating efforts to identify
      stages during the life cycle when biases develop. We investigated the demographic
      correlates of sex-ratio variation in two chromosome races of Rumex hastatulus, an
      annual, wind-pollinated colonizer of open habitats from the southern USA. We
      examined sex ratios in 46 populations and evaluated the hypothesis that the
      proximity of males in the local mating environment, through its influence on
      gametophytic selection, is the primary cause of female-biased sex ratios. Female
      biased sex ratios characterized most populations of R. hastatulus (mean sex ratio
      = 0.62), with significant female bias in 89% of populations. Large, high-density
      populations had the highest proportion of females, whereas smaller, low-density
      populations had sex ratios closer to equality. Progeny sex ratios were more
      female biased when males were in closer proximity to females, a result consistent
      with the gametophytic selection hypothesis. Our results suggest that interactions
      between demographic and genetic factors are probably the main cause of female
      biased sex ratios in R. hastatulus. The annual life cycle of this species may
      limit the scope for selection against males and may account for the weaker degree
      of bias in comparison with perennial Rumex species.

PMID- 23532762
TI  - Intravenous injection of neural progenitor cells facilitates angiogenesis after
      cerebral ischemia.
AB  - Earlier we demonstrated that the injection of neural progenitor cells (NPCs) has
      therapeutic potential for the improvement of learning dysfunction after cerebral
      ischemia. However, it remained to be clarified how transplantation of NPCs can
      improve ischemia-induced dysfunction. In this study, we examined whether
      intravenous injection of NPCs after cerebral ischemia could enhance angiogenesis
      by affecting the expression of angiogenic factors. The injection of NPCs on day 7
      after cerebral ischemia enhanced angiogenesis on day 28. Vascular endothelial
      growth factor (VEGF) and its receptor VEGFR2 were increased in expression by the
      NPC injection. The level of angiopoietin-1 (Ang-1), an angiogenic factor, but not
      that of Ang-2, which acts as an antagonist for the Ang-1 receptor, was also
      increased on day 28. In addition, the expression of Ang-1 receptor Tie2 was
      enhanced in brain capillaries. Furthermore, the amounts of tight junctional
      proteins, which are in the blood-brain barrier and whose expression occurs
      downstream of Ang-1/Tie2 signaling, were increased by the NPC injection. These
      results suggest that the NPC injection promoted angiogenesis through Ang-1/Tie2
      and/or VEGF/VEGFR2 signaling in brain capillaries after cerebral ischemia. Such
      signaling might have the potential for causing vascular stabilization and
      maturation for a long period after cerebral ischemia.

PMID- 23532763
TI  - Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac
      sodium current in dystrophin-deficient mdx (5cv) mice.
AB  - The cardiac voltage-gated sodium channel, Nav1.5, plays a central role in cardiac
      excitability and impulse propagation and associates with the dystrophin
      multiprotein complex at the lateral membrane of cardiomyocytes. It was previously
      shown that Nav1.5 protein content and the sodium current (l Na) were both
      decreased in cardiomyocytes of dystrophin-deficient mdx (5cv) mice. In this
      study, wild-type and mdx (5cv) mice were treated for 7 days with the proteasome
      inhibitor MG132 (10 MUg/Kg/24 h) using implanted osmotic mini pumps. MG132
      rescued both the total amount of Nav1.5 protein and l Na but, unlike in previous
      studies, de novo expression of dystrophin was not observed in skeletal or cardiac
      muscle. This study suggests that the reduced expression of Nav1.5 in dystrophin
      deficient cells is dependent on proteasomal degradation.

PMID- 23532765
TI  - Comparision of blood loss between computer assisted and conventional total knee
      arthroplasty.
AB  - BACKGROUND: Bleeding during total knee arthroplasty (TKA) can cause significant
      morbidity and mortality. One proposed benefit of computer assisted TKA is
      decreased bleeding as the femoral canal is not invaded. This study assessed blood
      loss between computer assisted surgery (CAS) and conventional TKA. MATERIALS AND
      METHODS: 73 consecutive patients (37 males, 36 females) underwent primary TKA
      between 2006 and 2009. Thirty eight patients underwent navigated TKA and 35
      underwent conventional TKA for symptomatic osteoarthritis of the knee. These
      patients were matched for age, gender, and body mass index (BMI). Average age was
      70.3 years (range 47-91 years). Mean BMI was 30 (range 17-49). Average
      preoperative hemoglobin was 13.26 g/dL (range 8.7-18.4 g/dL) in the navigated
      group and 13.47 g/dL (range 9.6-15.8 g/dL) in the conventional group (P = 0.9).
      Average tourniquet time was 110 min (range 90-150 min) in the navigated group and
      96.7 min (range 60-145 min) in the conventional group (P = 0.77). RESULTS:
      Average postoperative hemoglobin in the navigated group was 10.34 g/dL (range 7.5
      14.8 g/dL) and in the conventional group was 10.03 g/dL (range 7.5-12.2 g/dL) (P
      = 0.17). Six patients in both groups required blood transfusions. The mean drain
      collection was 599 mL (range 150-1370 mL) in the navigated group and 562 mL
      (range 750-1000 mL) in the conventional group (P = 0.1724). These results suggest
      that there is no significant reduction in blood loss in CAS TKA. CONCLUSION:
      These results suggest that there is no significant difference in blood loss in
      CAS TKA and conventional TKA. This study also highlights the heterogeneity of
      methods used in studies related to CAS TKA. We believe that there is a need for a
      large multicenter prospective randomized controlled trial to be performed before
      a consensus can be reached on the influence of CAS techniques on blood loss
      during primary TKA.

PMID- 23532764
TI  - Fetal hypoxia results in programming of aberrant angiotensin ii receptor
      expression patterns and kidney development.
AB  - AIMS: The present study tested the hypothesis that fetal hypoxia adversely
      affects kidney development in fetal and offspring rats and alter the expression
      patterns of angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors. METHODS:
      Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 last
      period of gestation) groups. Protein expression, in the offspring, was determined
      using western blot. RESULTS: Hypoxic treatment significantly decreased body and
      kidney weight in 21-day fetuses (E21) and 7-day neonates (P7). In 3-month-old
      offspring there were no significant differences in body and kidney weight between
      hypoxic and control animals. Fetal hypoxia had no effect on kidney AT1R density
      in E21 or P7, but significantly decreased kidney AT1R protein and mRNA abundance
      in both male and female adults. In contrast, kidney AT2R density was not affected
      by fetal hypoxia throughout the developmental stages studied. The hypoxia
      mediated reduction of nephron numbers was progressively from P7 worsened into the
      adulthood with females affected more than males. CONCLUSION: The results suggest
      that fetal hypoxia causes programming of aberrant kidney development and
      accelerates the aging process of the kidney during the postnatal development,
      which may contribute to an increased risk of cardiovascular disease.

PMID- 23532766
TI  - Is coronary CT angiography useful in diagnosing acute coronary syndromes in the
      Emergency Department?

PMID- 23532767
TI  - Barriers and Facilitators to Adoption of a Web-based Antibiotic Decision Support
      System.
AB  - OBJECTIVE: To measure clinicians' perceptions of barriers and facilitators to the
      adoption of a Computerised Decision Support System (CDSS) for antibiotic
      approval, and to examine the correlation between these perceptions and actual
      usage of the system by clinicians. METHODS: This study was conducted in a
      tertiary care university hospital of Melbourne, Australia. A survey tool
      comprising of demographic items and newly developed scales to measure clinicians'
      perceptions of barriers and facilitators to use of an CDSS was developed. Cross
      sectional mail surveys were sent to 250 Junior and Senior Medical Staff and
      Pharmacists in a tertiary care hospital. Cronbach's alpha was used to measure the
      reliability of the perceptions scales. One way ANOVA was used to assess the
      differences between participants' responses; Tamhane's test was used for post-hoc
      analysis. Pearson correlations were used to measure the relationship between the
      participants' scores on the scales and their actual use of the CDSS under study.
      RESULTS: The overall survey response rate was 54%. Cronbach's alpha for the
      perceived barrier and facilitator scales were 0.80 and 0.88, respectively. Senior
      medical staff perceived significantly more barriers than junior medical staff and
      pharmacists. Statistically significant differences were observed between the
      scores of the participants on a number of items on the perceived barriers and
      facilitators scales. Negative correlations were observed between the
      participants' scores on the perceived barriers scale and their use of the system.
      (r= -0.415, p= 0.001). CONCLUSIONS: The scales to measure perceived barriers and
      facilitators to adopt antibiotic CDSS have shown acceptable reliability and
      validity measures. Important differences exist between senior and junior medical
      staff about the barriers and facilitators to adopting the CDSS which may
      influence future use by clinicians.

PMID- 23532768
TI  - Sexually dimorphic response of TRPM2 inhibition following cardiac arrest-induced
      global cerebral ischemia in mice.
AB  - Transient global cerebral ischemia due to cardiac arrest followed by
      resuscitation (CA/CPR) causes significant neurological damage in vulnerable
      neuron populations within the brain, such as hippocampal CA1 neurons. In recent
      years, we have implicated the transient receptor potential M2 (TRPM2) channel as
      a mediator of ischemic injury to neurons. We previously demonstrated that genetic
      and pharmacological strategies that reduce TRPM2 function preferentially protect
      male neurons in vitro and reduce infarct volume following experimental stroke.
      Due to the narrow therapeutic window for intervention following ischemic stroke,
      it is important to assess the role of TRPM2 in other models of cerebral ischemia.
      Therefore, this study utilized a modified mouse model of CA/CPR to mimic more
      accurately the clinical condition by maintaining body and head temperatures near
      the physiological range throughout. Here, we report that inhibition of TRPM2
      activity with clotrimazole reduces hippocampal CA1 neuronal injury when
      administered 30 min after resuscitation from cardiac arrest. Consistent with our
      previous observations, neuroprotection was observed in male mice and no effect on
      injury was observed in the female. These findings provide further evidence for
      TRPM2 as a target for protection against cerebral ischemia in the male brain.

PMID- 23532769
TI  - Characterization of in vitro expanded bone marrow-derived mesenchymal stem cells
      isolated from experimental autoimmune encephalomyelitis mice.
AB  - Extensive experimental studies indicate that autologous bone marrow mesenchymal
      stem cells (BMSCs) are able to ameliorate experimental autoimmune
      encephalomyelitis (EAE) and potentially multiple sclerosis. However, the impact
      that the inflammatory environment present in EAE may have on the biological
      properties of BMSCs expanded in vitro for transplantation is yet to be clarified.
      It was investigated whether BMSCs isolated from EAE-induced C57bl6/J mice and
      expanded in vitro preserve the properties of BMSCs isolated from healthy donors
      (BMSCs-control). The mesenchymal origin, the differentiation potential, and the
      transcriptional expression profile of six histone-modifying genes were studied in
      both groups of BMSCs. BMSCs-EAE exhibited distinct morphology and larger size
      compared to BMSCs-control, higher degree of proliferation and apoptosis,
      differences in the adipogenesis and the osteogenesis induction, and differential
      expression of stromal markers and markers of progenitor and mature neuronal/glial
      cells. Moreover, BMSCs-EAE exhibited different expression patterns on a number of
      histone-modifying genes compared to controls. We recorded manifold differences,
      both phenotypical and functional, of in vitro expanded BMSCs-EAE in comparison to
      their healthy donor-derived counterparts that may be attributed to the
      inflammatory environment they originated from. Whether our findings may be of any
      clinical relevance needs to be clarified in future studies, in vivo. 

PMID- 23532770
TI  - Expression screening of cancer/testis genes in prostate cancer identifies NR6A1
      as a novel marker of disease progression and aggressiveness.
AB  - BACKGROUND: Cancer/Testis (CT) genes are expressed in male gonads, repressed in
      most healthy somatic tissues and de-repressed in various somatic malignancies
      including prostate cancers (PCa). Because of their specific expression signature
      and their associations with tumor aggressiveness and poor outcomes, CT genes are
      considered to be useful biomarkers and they are also targets for the development
      of new anti-cancer immunotherapies. The aim of this study was to identify novel
      CT genes associated with hormone-sensitive prostate cancer (HSPC), and castration
      resistant prostate cancer (CRPC). METHODS: To identify novel CT genes we screened
      genes for which transcripts were detected by RNA profiling specifically in normal
      testis and in either HSPC or CRPC as compared to normal prostate and 44 other
      healthy tissues using GeneChips. The expression and clinicopathological
      significance of a promising candidate--NR6A1--was examined in HSPC, CRPC, and
      metastatic site samples using tissue microarrays. RESULTS: We report the
      identification of 98 genes detected in CRPC, HSPC and testicular samples but not
      in the normal controls. Among them, cellular levels of NR6A1 were found to be
      higher in HSPC compared to normal prostate and further increased in metastatic
      lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly
      associated with a high Gleason score, advanced pT stage and cancer cell
      proliferation. CONCLUSIONS: Our results show that cellular levels of NR6A1 are
      correlated with disease progression in PCa. We suggest that this essential orphan
      nuclear receptor is a potential therapeutic target as well as a biomarker of PCa
      aggressiveness.

PMID- 23532771
TI  - Intracerebral pial arteriovenous fistula with large venous varix: A rare case
      report.
AB  - BACKGROUND: Intracerebral pial arteriovenous fistulas (AVFs) are rare vascular
      lesions of the brain. These lesions are composed of one or more direct arterial
      connection to a single venous channel without true intervening nidus and usually
      have associated venous varix or giant venous aneurysms. Intracerebral varices are
      occasionally associated with high-flow AVF, and usually treated by interrupting
      the feeding arteries leaving the varices intact. CASE DESCRIPTION: We report a
      rare case of a 24-year-old male with a single-channel pial AVF of the left
      cerebral hemisphere, which was fed by the left anterior cerebral artery (ACA) and
      was associated with large venous varix and continuous varicose venous dilatation.
      This superficially located varix was over 6 cm in diameter posing significant
      mass effect and had calcified walls. Direct surgical flow disconnection followed
      by removal of large varix resulted in complete disappearance of pial AVF without
      complication. CONCLUSION: Though endovascular occlusion of feeding arteries
      offers a simple and safe option, direct surgical removal should be considered in
      rare cases of intracerebral superficially located large AVF with calcified wall
      and mass effect.

PMID- 23532774
TI  - REM Sleep Behavior Disorder and Prodromal Neurodegeneration - Where Are We
      Headed?
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss
      of normal atonia during REM sleep, such that patients appear to act out their
      dreams. The most important implication of research into this area is that
      patients with idiopathic RBD are at very high risk of developing synuclein
      mediated neurodegenerative disease (Parkinson's disease [PD], dementia with Lewy
      bodies [DLB], and multiple system atrophy), with risk estimates that approximate
      40-65% at 10 years. Thus, RBD disorder is a very strong feature of prodromal
      synucleinopathy. This provides several opportunities for future research. First,
      patients with REM sleep behavior disorder can be studied to test other predictors
      of disease, which could potentially be applied to the general population. These
      studies have demonstrated that olfactory loss, decreased color vision, slowing on
      quantitative motor testing, and abnormal substantia nigra neuroimaging findings
      can predict clinical synucleinopathy. Second, prospectively studying patients
      with RBD allows a completely unprecedented opportunity to directly evaluate
      patients as they transition into clinical neurodegenerative disease. Studies
      assessing progression of markers of neurodegeneration in prodromal PD are
      beginning to appear. Third, RBD are very promising subjects for neuroprotective
      therapy trials because they have a high risk of disease conversion with a
      sufficiently long latency, which provides an opportunity for early intervention.
      As RBD research expands, collaboration between centers will become increasingly
      essential.

PMID- 23532775
TI  - Relative resistance to Mammalian target of rapamycin inhibition in vascular
      smooth muscle cells of diabetic donors.
AB  - BACKGROUND: Diabetes mellitus is associated with an increased risk of
      cardiovascular disease. Intimal thickening, a component of cardiovascular
      disease, entails the proliferation and migration of vascular smooth muscle cells
      (VSMCs). Inhibition of the mammalian target of rapamycin (mTOR) blocks VSMC
      proliferation, in part through an increase in the cyclin-dependent kinase
      inhibitor, p27(Kip1). The use of mTOR inhibitors, such as rapamycin, is effective
      clinically in inhibiting intimal thickening. This efficacy is reduced in diabetic
      subjects, however, suggesting a change in the role of the mTOR pathway in intimal
      thickening under diabetic conditions. METHODS: To examine whether diabetes
      induced changes in the role of mTOR in VSMC proliferation, we compared the
      response to rapamycin of human coronary artery VSMCs from diabetic (DM-huCASMC
      [human coronary artery smooth muscle cell]) and nondiabetic (ND-huCASMC)
      subjects. RESULTS: The DM-huCASMCs exhibited a relative resistance to rapamycin's
      inhibition of proliferation. Activation of the mTOR effector p70(S6kinase) was
      inhibited in rapamycin-treated DM-huCASMCs as in ND-huCASMCs. While ND-huCASMCs
      exhibited the normal increase in p27(Kip1) in response to rapamycin treatment,
      the DM-huCASMCs did not. Additionally, activation of the extracellular signal
      response kinase pathway was increased in the DM-huCASMCs, suggesting a potential
      pathway mediating the mTOR-independent decrease in p27(Kip1). CONCLUSION: We
      conclude that diabetes is accompanied by a relative resistance to the effects of
      mTOR inhibition on VSMC proliferation through a loss of mTOR's effects on
      p27(Kip1) levels. These data provide insight into the effects of insulin
      resistance on the role of mTOR in regulating intimal thickening.

PMID- 23532776
TI  - Characterization of the Population Demographics and the MSP-1 Block 2 Allele Gene
      Frequencies of P. falciparum Infected Individuals in Davao, Philippines.
AB  - Plasmodium falciparum is one of the causative agents of malaria in humans. This
      parasite causes the most severe forms of the disease. In order to combat the
      disease, it is important to have knowledge about the parasite and its interaction
      with its host. In this study, we profiled 74 patients admitted to hospital in
      Tagum, Davao, Philippines who were confirmed to be infected with P. falciparum.
      We correlated the age, sex and parasite load with malaria severity and show that
      among these, only sex is correlated with disease severity in this population. In
      addition, we profiled the MSP-1 block 2 allele distribution in the population and
      found that the most abundant allele form was K1, followed by MAD20. The RO33
      allele form was the rarest allele in this population.

PMID- 23532777
TI  - A scientometric analysis of 20 years of research on breast reconstruction
      surgery: a guide for research design and journal selection.
AB  - BACKGROUND: Breast reconstruction refers to the rebuilding of a woman's breast
      using autologous tissue or prosthetic material to form a natural-looking breast.
      It is increasingly offered to women undergoing mastectomy for breast cancer.
      However, there is no systematic analysis available for the expanding area of
      research on breast reconstruction. METHODS: A bibliometric method was used to
      obtain a view of the scientific production about breast reconstruction by data
      extracted from the Institute for Scientific Information (ISI). Specific
      parameters were retrieved from the ISI. Articles about breast reconstruction were
      analyzed to obtain a view of the topic's structure, history, and document
      relationships using HistCite software. Trends in the most influential
      publications and authors were analyzed. RESULTS: The number of articles was
      constantly increasing. Most highly cited articles described the methods of flap
      construction in the surgery. Other highly cited articles discussed the
      psychological or emotional aspects of breast reconstruction, skin sparing
      mastectomy, and breast reconstruction in the irradiated breast. CONCLUSIONS: This
      was the first breast reconstruction scientometric analysis, representing the
      characteristics of papers and the trends of scientific production. A constant
      increase in the number of breast reconstruction papers and also the increasing
      number of citations shows that there is an increasing interest in this area of
      medical science. It seems that most of the research in this field is focused on
      the technical aspects of surgery.

PMID- 23532778
TI  - Euthanasia is not medical treatment.
AB  - INTRODUCTION OR BACKGROUND: The public assumes that if euthanasia and assisted
      suicide were to be legalized they would be carried out by physicians. SOURCES OF
      DATA: In furthering critical analysis, we supplement the discourse in the ethics
      and palliative care literature with that from medical education and evolving
      jurisprudence. AREAS OF AGREEMENT: Both proponents and opponents agree that the
      values of respect for human life and for individuals' autonomy are relevant to
      the debate. AREAS OF CONTROVERSY: Advocates of euthanasia and assisted suicide
      give priority to the right to personal autonomy and avoid discussions of harmful
      impacts of these practices on medicine, law and society. Opponents give priority
      to respect for life and identify such harmful effects. These both require
      euthanasia to remain legally prohibited. GROWING POINTS: Proposals are emerging
      that if society legalizes euthanasia it should not be mandated to physicians.
      AREAS TIMELY FOR DEVELOPING RESEARCH: The impact of characterizing euthanasia as
      'medical treatment' on physicians' professional identity and on the institutions
      of medicine and law should be examined in jurisdictions where assisted suicide
      and euthanasia have been de-criminalized.

PMID- 23532779
TI  - Coronary stents: historical development, current status and future directions.
AB  - INTRODUCTION: Coronary angioplasty with stenting has revolutionized the treatment
      of coronary artery disease. This article describes the history of coronary
      angioplasty and stenting, reviews the contemporary stents and recommendations and
      highlights the on-going work and potential future directions. SOURCES OF DATA:
      This review examined the data on coronary stents available in PubMed. AREAS OF
      AGREEMENT: Coronary artery stenting is the treatment of choice for patients
      requiring coronary angioplasty. Stents, and particularly drug-eluting stents,
      reduce the risk of restenosis, but may be associated with the hazard of late
      stent thrombosis. Dual anti-platelet treatment is recommended for patients
      receiving coronary stents. AREAS OF CONTROVERSY: The selection of stents for
      various lesions and patients and the duration of anti-platelet therapy remain
      debated areas. AREAS TIMELY FOR DEVELOPING RESEARCH: There are on-going
      preclinical and clinical studies to develop better stent platforms, more
      biocompatible polymers, novel anti-proliferative and anti-platelet drugs, pro
      healing stents and bioresorbable scaffolds.

PMID- 23532781
TI  - Non-target screening of veterinary drugs using tandem mass spectrometry on
      SmartMass.
AB  - Non-target screening of veterinary drugs using tandem mass spectrometric data was
      performed on the SmartMass platform. This newly developed software uses the
      characteristic fragmentation patterns (CFP) to identify chemicals, especially
      those containing particular substructures. A mixture of 17 sulfonamides was
      separated by ultra performance liquid chromatography (UPLC), and SmartMass was
      used to process the tandem mass spectrometry (MS/MS) data acquired on an Orbitrap
      mass spectrometer. The data were automatically extracted, and each sulfonamide
      was recognized and analyzed with a prebuilt analysis rule. By using this
      software, over 98% of the false candidate structures were eliminated, and all the
      correct structures were found within the top 10 of the ranking lists.
      Furthermore, SmartMass could also be used to identify slightly modified
      contraband drugs and metabolites with simple prebuilt rules.

PMID- 23532780
TI  - Promoting integrated approaches to reducing health inequities among low-income
      workers: applying a social ecological framework.
AB  - BACKGROUND: Nearly one of every three workers in the United States is low-income.
      Low-income populations have a lower life expectancy and greater rates of chronic
      diseases compared to those with higher incomes. Low- income workers face hazards
      in their workplaces as well as in their communities. Developing integrated public
      health programs that address these combined health hazards, especially the
      interaction of occupational and non-occupational risk factors, can promote
      greater health equity. METHODS: We apply a social-ecological perspective in
      considering ways to improve the health of the low-income working population
      through integrated health protection and health promotion programs initiated in
      four different settings: the worksite, state and local health departments,
      community health centers, and community-based organizations. RESULTS: Examples of
      successful approaches to developing integrated programs are presented in each of
      these settings. These examples illustrate several complementary venues for public
      health programs that consider the complex interplay between work-related and non
      work-related factors, that integrate health protection with health promotion and
      that are delivered at multiple levels to improve health for low-income workers.
      CONCLUSIONS: Whether at the workplace or in the community, employers, workers,
      labor and community advocates, in partnership with public health practitioners,
      can deliver comprehensive and integrated health protection and health promotion
      programs. Recommendations for improved research, training, and coordination among
      health departments, health practitioners, worksites and community organizations
      are proposed.

PMID- 23532782
TI  - Using metal complex ion-molecule reactions in a miniature rectilinear ion trap
      mass spectrometer to detect chemical warfare agents.
AB  - The gas-phase reactions of a series of coordinatively unsaturated [Ni(L)n](y+)
      complexes, where L is a nitrogen-containing ligand, with chemical warfare agent
      (CWA) simulants in a miniature rectilinear ion trap mass spectrometer were
      investigated as part of a new approach to detect CWAs. Results show that upon
      entering the vacuum system via a poly(dimethylsiloxane) (PDMS) membrane
      introduction, low concentrations of several CWA simulants, including dipropyl
      sulfide (simulant for mustard gas), acetonitrile (simulant for the nerve agent
      tabun), and diethyl phosphite (simulant for nerve agents sarin, soman, tabun, and
      VX), can react with metal complex ions generated by electrospray ionization
      (ESI), thereby providing a sensitive means of detecting these compounds. The
      [Ni(L)n](2+) complexes are found to be particularly reactive with the simulants
      of mustard gas and tabun, allowing their detection at low parts-per-billion (ppb)
      levels. These detection limits are well below reported exposure limits for these
      CWAs, which indicates the applicability of this new approach, and are about two
      orders of magnitude lower than electron ionization detection limits on the same
      mass spectrometer. The use of coordinatively unsaturated metal complexes as
      reagent ions offers the possibility of further tuning the ion-molecule chemistry
      so that desired compounds can be detected selectively or at even lower
      concentrations.

PMID- 23532783
TI  - Optimizing booster chlorination in water distribution networks: a water quality
      index approach.
AB  - The optimization of chlorine dosage and the number of booster locations is an
      important aspect of water quality management in distribution networks. Booster
      chlorination helps to maintain uniformity and adequacy of free residual chlorine
      concentration, essential for safeguarding against microbiological contamination.
      Higher chlorine dosages increase free residual chlorine concentration but
      generate harmful by-products, in addition to taste and odor complaints. It is
      possible to address these microbial, chemical, and aesthetic water quality issues
      through free residual chlorine concentration. Estimating a water quality index
      (WQI) based on regulatory chlorine thresholds for microbial, chemical, and
      aesthetics criteria can help engineers make intelligent decisions. An innovative
      scheme for maintaining adequate residual chlorine with optimal chlorine dosages
      and numbers of booster locations was established based on a proposed WQI. The
      City of Kelowna (BC, Canada) water distribution network served to demonstrate the
      application of the proposed scheme. Temporal free residual chlorine concentration
      predicted with EPANET software was used to estimate the WQI, later coupled with
      an optimization scheme. Preliminary temporal and spatial analyses identified
      critical zones (relatively poor water quality) in the distribution network. The
      model may also prove useful for small or rural communities where free residual
      chlorine is considered as the only water quality criterion. 

PMID- 23532784
TI  - Diurnal variations in bacterial and viral production in Cochin estuary, India.
AB  - Microbes play a central role in the decomposition and remineralization of organic
      matter and recycling of nutrients in aquatic environments. In this study, we
      examined the influence of physical, chemical, and biological parameters on the
      rate of bacterial production (BP) and viral production (VP) with respect to
      primary production over a diurnal period in Cochin estuary. Time series
      measurements were made every 2 h for 12 h (6 a.m.-6 p.m.) during periods of low
      and high salinities. The light intensity as photosynthetically active radiation,
      temperature, salinity, nutrients like NO3-N, SiO4-Si, and PO4-P, and chlorophyll
      a (Chl a) were measured along with BP, VP, and net primary production (NPP). NPP
      showed a strong positive correlation with light and Chl a (r (2) = 0.56 and 0.47,
      respectively), while VP showed a strong positive correlation with light,
      salinity, and Chl a (r (2) = 0.37, 0.58, and 0.37, respectively) and a negative
      correlation with BP (r (2) = -0.39) at P <= 0.05. We observed a diurnal pattern
      in BP but did not have any significant correlation with light. Similar diurnal
      pattern was seen in VP, the peak of which was in succession with BP, suggesting
      that virus-mediated lysis plays an important role in loss processes of bacteria
      in Cochin estuary. The results of our study highlight the light-dependent and
      physicochemical-dependent diurnal variation in virioplankton production in a
      tropical estuarine ecosystem. 

PMID- 23532785
TI  - Prevalence and genetic diversity of norovirus infection in Tunisian children
      (2007-2010).
AB  - Viral gastroenteritis can be a life-threatening disease in infants and young
      children, especially in developing countries. The aim of this study was to
      continue the epidemiological surveillance of norovirus (NoV) infections in
      Tunisian children suffering from acute gastroenteritis. Surveillance was
      initiated in January 2003, to monitor potential variations in strains over time,
      in terms of frequency and diversity of NoV genotypes, and more particularly the
      potential emergence of new GII.4 variants following the 2004 Hunter variant. From
      April 2007 to April 2010, a total of 407 stool specimens were collected from
      sporadic cases (238 inpatients and 169 outpatients). Furthermore, 28 stool
      samples were collected from children involved in 3 gastroenteritis outbreaks.
      Stool specimens were screened for NoV genogroup I (GI) and II (GII) by RT-PCR.
      NoV strains were genotyped, and variants identified, based on sequence and
      phylogenetic analyses of the polymerase and capsid genes. NoVs were detected in
      38 sporadic cases (9.3%) and 21 epidemic cases (75%). Great diversity was
      observed throughout the period, with seven distinct NoV genotypes characterized
      in sporadic cases, and three in outbreaks. GIIb/II.3 and GII.4 were predominant
      globally, with fluctuations of their prevalence over time. Interestingly, the
      Hunter variant, which was the unique GII.4 variant observed from 2003 to April
      2007 in the region of Monastir, was replaced by the 2006b variant. NoV is an
      important enteropathogen responsible for viral gastroenteritis among infants and
      children in Tunisia, and the infecting strains between 2007 and 2010 were
      different from those in previous years.

PMID- 23532787
TI  - Noncardiogenic pulmonary edema.
AB  - Pulmonary edema may develop secondary to several cardiogenic and noncardiogenic
      conditions. Cardiogenic pulmonary edema (CPE) is associated with heart disease,
      an elevation in left atrial pressure, and an increase in pulmonary venous and
      capillary pressures. In contrast, noncardiogenic pulmonary edema (NCPE) can occur
      without pathologic cardiac disease and an elevation in left atrial pressure. NCPE
      has been associated with an increase in capillary membrane permeability with or
      without an increase in hydrostatic pressure. Signalment, history, and thoracic
      radiography may help distinguish NCPE from CPE. Some types of NCPE are self
      limiting, and treatment may be largely supportive; others may require
      pharmacologic intervention and advanced respiratory support.

PMID- 23532786
TI  - Sea star populations diverge by positive selection at a sperm-egg compatibility
      locus.
AB  - Fertilization proteins of marine broadcast spawning species often show signals of
      positive selection. Among geographically isolated populations, positive selection
      within populations can lead to differences between them, and may result in
      reproductive isolation upon secondary contact. Here, we test for positive
      selection in the reproductive compatibility locus, bindin, in two populations of
      a sea star on either side of a phylogeographic break. We find evidence for
      positive selection at codon sites in both populations, which are under neutral or
      purifying selection in the reciprocal population. The signal of positive
      selection is stronger and more robust in the population where effective
      population size is larger and bindin diversity is greater. In addition, we find
      high variation in coding sequence length caused by large indels at two repetitive
      domains within the gene, with greater length diversity in the larger population.
      These findings provide evidence of population-divergent positive selection in a
      fertilization compatibility locus, and suggest that sexual selection can lead to
      reproductive divergence between conspecific marine populations.

PMID- 23532788
TI  - Equine laparoscopy: abdominal access techniques.

PMID- 23532789
TI  - Sacroiliac injuries in horses.
AB  - This article reviews the pathology, diagnosis, and treatment of sacroiliac joint
      injuries. These injuries can be acute or chronic and can involve soft tissue
      structures surrounding the joint or the bony structures of the joint. The several
      diagnostic modalities for sacroiliac injuries vary in usefulness and
      accessibility. Treatment of sacroiliac problems is usually supportive and
      nonspecific and includes the use of antiinflammatory medications and an
      appropriate exercise regimen. The prognosis depends on the cause, but severe
      injuries can limit a horse's future athletic activity.

PMID- 23532790
TI  - Excellence in exotics: enriching the lives of small exotic pet mammals.

PMID- 23532791
TI  - Excellence in exotics: case report: Encephalitozoon cuniculi-associated
      phacoclastic uveitis in a dwarf rabbit.

PMID- 23532792
TI  - Excellence in exotics: practice tip: nasolacrimal duct flushes in rabbits.

PMID- 23532793
TI  - Rapid high-yield N-acylation of aminothiols: N-acetylglutathione and N
      acetylhomocysteine and their thiol pK(a) values.
AB  - Methodology for the rapid N-acylation of aminothiols in aqueous solution using
      procedures commonly employed in biochemical studies is described here.
      Glutathione disulfide (GSSG) and homocystine were diN-acetylated in ~100% yield
      in 0.1 M aqueous NaHCO3 (pH 8.5) at room temperature by 2.5 equiv of the
      activated ester, N-hydroxysulfosuccinimidyl acetate, an efficient water-soluble
      acetylating reagent. Following acetone precipitation, diN-acetylGSSG was further
      purified and desalted on a strong anion-exchange (SAX) cartridge. DiN
      acetylhomocystine was simultaneously purified and desalted on a C18 cartridge.
      The N-acetylated aminothiols were generated using gel-immobilized tris(2
      carboxyethyl)phosphine as a reductant, which obviated the need for further
      purification. Alternatively, disulfide exchange with dissolved dithiothreitol
      yielded N-acetylglutathione, which was purified on the SAX cartridge. pH
      titrations of N-acetylglutathione (8.99) and N-acetylhomocysteine (9.66) as well
      as those of commercially available N-acetylcysteine (9.53) and N
      acetylpenicillamine (10.21) yielded pK(a) (SH) values of importance for
      biological studies.

PMID- 23532794
TI  - Short, fine and WHO asbestos fibers in the lungs of quebec workers with an
      asbestos-related disease.
AB  - BACKGROUND: The possible role of short asbestos fibers in the development of
      asbestos-related diseases and availability of lung fiber burden data prompted
      this study on the relationships between fiber characteristics and asbestos
      related diseases among compensated workers. METHODS: Data collected between 1988
      and 2007 for compensation purposes were used; lung asbestos fibers content of 123
      Quebec workers are described according to socio-demographic characteristics, job
      histories and diseases (asbestosis, mesothelioma, lung cancer). RESULTS: Most
      workers (85%) presented chrysotile fibers in their lungs, and respectively 76%,
      64%, and 43% had tremolite, amosite, and crocidolite. Half of the total fibers
      were short, 30% were thin fibers and 20% corresponded to the World Health
      Organization definition of fibers (length >= 5 MUm, diameter >= 0.2 and <3 MUm).
      Chrysotile fibers were still observed in the lungs of workers 30 years or more
      after last exposure. CONCLUSION: Our findings stress the relevance of considering
      several dimensional criteria to characterize health risks associated with
      asbestos inhalation.

PMID- 23532795
TI  - Attention-dependent modulation of neural activity in primary sensorimotor cortex.
AB  - Although motor tasks at most times do not require much attention, there are
      findings that attention can alter neuronal activity not only in higher motor
      areas but also within the primary sensorimotor cortex. However, these findings
      are equivocal as attention effects were investigated only in either the dominant
      or the nondominant hand; attention was operationalized either as concentration
      (i.e., attention directed to motor task) or as distraction (i.e., attention
      directed away from motor task), the complexity of motor tasks varied and almost
      no left-handers were studied. Therefore, in this study, both right- and left
      handers were investigated with an externally paced button press task in which
      subjects typed with the index finger of the dominant, nondominant, or both hands.
      We introduced four different attention levels: attention-modulation-free,
      distraction (counting backward), concentration on the moving finger, and divided
      concentration during bimanual movement. We found that distraction reduced
      neuronal activity in both contra- and ipsilateral primary sensorimotor cortex
      when the nondominant hand was tapping in both handedness groups. At the same
      time, distraction activated the dorsal frontoparietal attention network and
      deactivated the ventral default network. We conclude that difficulty and training
      status of both the motor and cognitive task, as well as usage of the dominant
      versus the nondominant hand, are crucial for the presence and magnitude of
      attention effects on sensorimotor cortex activity. In the case of a very simple
      button press task, attention modulation is seen for the nondominant hand under
      distraction and in both handedness groups.

PMID- 23532796
TI  - Disability and marginal utility of income: evidence from hypothetical choices.
AB  - It is often assumed that disability reduces the marginal utility of income. In
      this article, individuals' marginal utility of income in two states-(i) paralyzed
      in both legs from birth and (ii) not mobility impaired at all-is measured through
      hypothetical choices between imagined lotteries behind a so-called veil of
      ignorance. The outcomes of the lotteries include both income and disability
      status. It is found that most people have higher marginal utility when paralyzed
      than when not mobility impaired at all. The two marginal utilities are evaluated
      at the same levels of income. Having personal experience of mobility impairment
      and supporting the Left Party, the Social Democratic Party, the Green Party, or
      the Liberal Party are associated with having a higher marginal utility when
      paralyzed. The results suggest that more than full insurance of income losses
      connected to being disabled is optimal. The results further suggest that, given a
      utilitarian social welfare function, resources should be transferred to rather
      than from disabled people. Finally, if the transfers are not large enough to
      smooth out the marginal utilities of the disabled and the nondisabled,
      distributional weights based on disability status should be used in cost-benefit
      analysis.

PMID- 23532797
TI  - High-grade prostatic intraepithelial neoplasia (HGPIN) and topographical
      distribution in 1,374 prostatectomy specimens: existence of HGPIN near prostate
      cancer.
AB  - PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is believed to be
      a precursor of prostate cancer (PCa). This study evaluated whether HGPIN was
      located close to PCa in whole radical prostatectomy specimens (RPSs). MATERIALS
      AND METHODS: We evaluated 1,374 prostate specimens from 1999 to 2010 using a cMDX
      based map model of the prostate. The distribution of 10,439 PCa foci was analyzed
      and visualized on a heat map. The color gradient of the heat map was reduced to
      six colors representing the frequency classification of the relative frequency of
      PCa using an image posterization effect. We defined 22 regions in the prostate
      according to the frequency of PCa occurrence. Seven hundred ninety RPSs
      containing 6,374 PCa foci and 4,502 HGPIN foci were evaluated. The topographical
      association between PCa and HGPIN in the RPSs was analyzed by estimating the
      frequencies of PCa and HGPIN in 22 regions. A logistic regression analysis was
      performed to assess the odds ratios of HGPIN for the presence of PCa in 22
      regions. RESULTS: Fifty-eight percent of PCa specimens included HGPIN and had
      significantly more favorable Gleason scores, lower PSA levels and smaller
      relative tumor volumes than isolated PCa specimens. HGPIN (68%) and PCa (69%)
      were predominantly localized to the apical half of the prostate. HGPIN was mainly
      concentrated in the peripheral zone medial to regions with high PCa frequencies.
      Upon logistic regression analysis, HGPIN was a significant predictor of PCa co
      existence in 11 regions. CONCLUSIONS: HGPIN was located adjacent to PCa in whole
      RPSs. PCa concomitant with HGPIN had more favorable pathologic features than
      isolated PCa.

PMID- 23532798
TI  - Central calcaneal osteotomy for correction of flexible pes planovalgus deformity.
AB  - BACKGROUND: Lateral column lengthening procedures have been extensively reported
      either as primary procedures or adjuncts to combined soft tissue procedures and
      osteotomies for the correction of the pes planovalgus deformity. There is also
      considerable debate as to the ideal procedure that is not followed by recurrence
      and obviates the need for revision surgeries and minimizes complications. We
      describe a technique and present the clinical results of lateral column
      lengthening that provides a powerful correction to restore normal foot alignment.
      METHODS: We retrospectively reviewed 26 feet in 21 patients with a mean age of
      35.4 years (range, 12-75) over an average follow-up period of 71 months (range,
      12-147) who underwent reconstructive surgery for flexible pes planovalgus foot.
      The reconstructive procedures included a central calcaneal osteotomy in all
      patients, a medial column stabilization procedure, flexor digitorium transfer
      (FDL), and a gastrocnemius or Achilles tendon lengthening. Clinical evaluation
      was carried out with the AOFAS ankle-hindfoot scores. Standard weight-bearing
      anterior posterior (AP) and lateral radiographs before surgery and at follow-up
      were analyzed for radiographic parameters of correction. RESULTS: The median
      AOFAS score increased from 50 to 90. Two patients reported dissatisfaction with
      the result. There were no nonunions nor complications related to hardware.
      Radiographic improvement of the talonavicular coverage angle was a 74% change
      from baseline value. All radiographic parameters improved (P < .001) except the
      lateral talocalcaneal angle (P = .48). No secondary subsidence of the arch was
      observed within the follow-up time. CONCLUSION: Correction of flexible pes
      planovalgus deformity with a central calcaneal osteotomy was an effective,
      reproducible method to restore normal foot alignment and good function. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 23532800
TI  - Neurophysiological correlates of anhedonia in feedback processing.
AB  - Disturbances in feedback processing and a dysregulation of the neural circuit in
      which the cingulate cortex plays a key role have been frequently observed in
      depression. Since depression is a heterogeneous disease, instead of focusing on
      the depressive state in general, this study investigated the relations between
      the two core symptoms of depression, i.e., depressed mood and anhedonia, and the
      neural correlates of feedback processing using fMRI. The focus was on the
      different subdivisions of the anterior cingulate cortex (ACC). Undergraduates
      with varying levels of depressed mood and anhedonia performed a time-estimation
      task in which they received positive and negative feedback that was either valid
      or invalid (i.e., related vs. unrelated to actual performance). The rostral
      cingulate zone (RCZ), corresponding to the dorsal part of the ACC, was less
      active in response to feedback in more anhedonic individuals, after correcting
      for the influence of depressed mood, whereas the subgenual ACC was more active in
      these individuals. Task performance was not affected by anhedonia, however. No
      statistically significant effects were found for depressed mood above and beyond
      the effects of anhedonia. This study therefore implies that increasing levels of
      anhedonia involve changes in the neural circuitry underlying feedback processing.

PMID- 23532799
TI  - A randomized trial of a Facebook-based physical activity intervention for young
      adult cancer survivors.
AB  - PURPOSE: Over half of young adult cancer survivors do not meet physical activity
      (PA) guidelines. PA interventions can enhance health and quality of life among
      young adult cancer survivors. However, few exercise interventions have been
      designed and tested in this population. This study evaluated the feasibility and
      preliminary efficacy of a 12-week, Facebook-based intervention (FITNET) aimed at
      increasing moderate-to-vigorous intensity PA compared with a Facebook-based self
      help comparison (SC) condition. METHODS: Young adult cancer survivors (n = 86)
      were randomly assigned to the FITNET or SC group. All participants were asked to
      complete self-administered online questionnaires at baseline and after 12 weeks.
      RESULTS: Seventy-seven percent of participants completed postintervention
      assessments, and most participants reported using intervention components as
      intended. Participants in both groups would recommend the program to other young
      adult cancer survivors (FITNET, 46.9 vs. SC, 61.8 %; p = 0.225). Over 12 weeks,
      both groups increased self-reported weekly minutes of moderate-to-vigorous PA
      (FITNET, 67 min/week (p = 0.009) vs. SC, 46 min/week (p = 0.045)), with no
      significant difference between groups. Increases in light PA were 135 min/week
      greater in the FITNET group relative to the SC group (p = 0.032), and the FITNET
      group reported significant weight loss over time (-2.1 kg, p = 0.004; p = 0.083
      between groups). CONCLUSION: Facebook-based intervention approaches demonstrated
      potential for increasing PA in young adult cancer survivors. IMPLICATIONS FOR
      CANCER SURVIVORS: Social networking sites may be a feasible way for young adult
      cancer survivors to receive health information and support to promote PA and
      healthy behaviors.

PMID- 23532801
TI  - Economic evaluation of 5-grass pollen tablets versus placebo in the treatment of
      allergic rhinitis in adults.
AB  - BACKGROUND: Allergen immunotherapy (AIT) is aimed at modifying the immune
      response to a causative allergen, thereby reducing clinical symptoms and
      symptomatic medication intake and improving quality of life. Long-term AIT
      research has led to the development of 5-grass pollen tablets, currently
      indicated for the treatment of grass pollen-induced allergic rhinitis (AR).
      METHODS: A post-hoc analysis was conducted using the Average Adjusted Symptom
      Score (AAdSS) to compare the effect of treatment of AR with 5-grass pollen
      tablets versus placebo treatment. Using the results of the VO34.04 and VO53.06
      trials and economic data, cost-effectiveness analysis of 5-grass pollen tablet
      treatment was performed from the Italian third-party payer perspective with cost
      data derived from a study of 2008 updated to 2011. Also a societal perspective
      was considered by using the costs related to the losses of productivity by
      following the human capital approach. Using the results of the analysis, the
      estimated receiver-operating characteristic curve was plotted to evaluate
      medication effectiveness in terms of quality-adjusted life years (QALYs) and a
      decision tree constructed to model the possible outcomes and costs for adults and
      paediatric patients with a low, medium, and high AAdSS. Finally, probabilistic
      sensitivity analysis was conducted to test the robustness of the results as well
      as their consistency at an assumed cost-effectiveness threshold of ? 30,000/QALY.
      RESULTS: The results indicate that compared to the placebo, the 5-grass pollen
      tablet treatment provides a benefit of 0.127 QALYs in medium AAdSS patients and
      of 0.143 QALYs in high AAdSS patients. The 5-grass pollen tablet treatment was
      found to cost ? 1,024/QALY for patients with a medium AAdSS and ? 1,035/QALY for
      patients with a high AAdSS. Of all the simulations performed in the probabilistic
      sensitivity analysis, 99 % indicated that the incremental cost-effectiveness
      ratio of the 5-grass pollen tablet treatment was below the threshold of ?
      30,000/QALY in patients with medium and high AAdSS, whereas it was found to be
      dominated in 67 % of simulations related to patients with low AAdSS. CONCLUSION:
      The 5-grass pollen tablet is a cost-effective treatment for adult AR patients
      with a medium or high AAdSS. This finding should be carefully considered when
      deciding the management strategy for these patients.

PMID- 23532802
TI  - Role of interleukin-28B polymorphism as a predictor of sustained virological
      response in patients with chronic hepatitis C treated with triple therapy: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Chronic hepatitis C represents an important health
      problem. The aim of our meta-analysis was to establish the role of reference
      single nucleotide (rs) 12979860 allele of interleukin-28B (IL28B) CC versus CT+TT
      genotype (the most researched allele of IL28B) as a predictor of sustained
      virological response (SVR) in patients with chronic hepatitis C treated with
      triple therapy. METHODS: The PubMed, MEDLINE, Lilacs, Scopus, Ovid, EMBASE,
      Cochrane and Medscape databases as well as abstract books from important
      gastroenterology and hepatology meetings were searched for all studies published
      until 15 July 2012 that analysed the relationship between the polymorphism of
      IL28B and SVR in patients with chronic hepatitis C, genotype 1, treated with
      pegylated interferon + ribavirin + direct antiviral agents (telaprevir or
      boceprevir). The following keywords were used: IL28B polymorphism, chronic
      hepatitis C, sustained virological response, SVR, triple therapy, telaprevir,
      boceprevir. RESULTS: Odds ratios (ORs) with 95 % confidence intervals were pooled
      from five study populations (1,641 cases) using a random-effects model. The SVR
      rate was significantly higher in patients with the CC genotype of IL28B than in
      those with non-CC genotypes (CT and TT): OR = 3.91 (95 % CI 2.11-7.28), p <
      0.0001. Higher SVR rates were obtained in chronic hepatitis C patients with the
      CC genotype of IL28B, regardless of their therapeutic status (naive patients: OR
      = 3.99 [95 % CI 1.67-9.51], p < 0.0001; and previously treated ones: OR = 2.15
      [95 % CI 1.35-3.43], p = 0.001). CONCLUSION: IL28B polymorphism seems to
      influence the SVR rate in patients with chronic hepatitis C treated with triple
      therapy, but further studies are needed to clarify the mechanism and the
      influence of other factors on the SVR rates.

PMID- 23532803
TI  - Correlation of posterior tibial slope with metaphysio-diaphyseal angle in total
      knee arthroplasty: A radiological study.
AB  - BACKGROUND: Posterior tibial slope (PTS) is an important factor affecting
      postoperative range of motion (ROM) following total knee arthroplasty (TKA).
      Metaphysio-diaphyseal angle (MDA) is a new entity defined as angle between
      proximal anatomical axis and metaphyseal axis of tibia. This study was undertaken
      to determine PTS in Indian patients and find its correlation with MDA of tibia.
      Accuracy of extramedullary jigs and the influence of MDA on the accuracy was also
      evaluated. This study is a retrospective analysis of prospectively collected data
      in a tertiary healthcare center. MATERIALS AND METHODS: Data of 100 consecutive
      patients undergoing TKA in a single center by a single surgeon was analyzed.
      Posterior cruciate ligament (PCL) substituting TKA was done with same jig to
      achieve different PTS in different patients. MDA, preoperative PTS and
      postoperative PTS were calculated. The data was analyzed using appropriate
      statistical analysis. RESULTS: Mean preoperative PTS was 11.64 degrees  and mean
      MDA was 23.76 degrees  with a strong correlation between them (Pearson's
      coefficient 0.72). Extramedullary jigs were accurate in 53% cases. In remaining
      47%, postoperative PTS was less than planned PTS in 30%, and more in 17%. Mean
      postoperative PTS was 2.54 degrees . In patients with MDA < 20 degrees ,
      postoperative PTS was significantly less (P = 0.0176) compared with those with
      MDA > 20 degrees . CONCLUSIONS: The study establishes the positive correlation
      between MDA and PTS in Indians; and that MDA is an independent factor affecting
      accuracy of extramedullary jigs in TKA.

PMID- 23532804
TI  - Neurosurgical management of massive cerebellar infarct outcome in 53 patients.
AB  - BACKGROUND: Massive ischemic cerebellar infarct (MICI) is a main source of
      stroke, which can lead to severe morbidity and mortality. There is no consensus
      in medical literature for the management of MICI. The choice is made between
      placing an external ventricular drainage, suboccipital decompressive craniectomy,
      and removal of necrotic tissue or conservative treatment. There are not many
      prospective studies, done on this subject. METHODS: We retrospectively analyzed
      the clinical features, and imaging studies of 53 patients with MICI who had been
      treated by surgery or conservative treatment between January 2000 and December
      2008 at the Department of Neurosurgery of the general hospital of Fort de France
      in Martinique. A total of 25 patients underwent surgery and 28 were treated
      medically. RESULTS: The results show significantly better outcomes in the
      operated patients compared with the patients treated medically; Operated comatose
      patients demonstrated significant improvement in their Glasgow coma score (GCS)
      score with only two deaths. Whereas, nonoperated comatose patients lost points in
      their GCS with four deaths. CONCLUSION: The results of our study suggest that
      surgery may be an effective procedure and quite helpful for MICI in majority of
      cases.

PMID- 23532806
TI  - New changes in EAPD.

PMID- 23532805
TI  - Potential immunogenic polypeptides of Burkholderia pseudomallei identified by
      shotgun expression library and evaluation of their efficacy for serodiagnosis of
      melioidosis.
AB  - The search for novel immunogenic polypeptides to improve the accuracy and
      reliability of serologic diagnostic methods for Burkholderia pseudomallei
      infection is ongoing. We employed a rapid and efficient approach to identify such
      polypeptides with sera from melioidosis patients using a small insert genomic
      expression library created from clinically confirmed local virulent isolates of
      B. pseudomallei. After 2 rounds of immunoscreening, 6 sero-positive clones
      expressing immunogenic peptides were sequenced and their identities were:
      benzoate 1,2-dioxygenase beta subunit, a putative 200 kDa antigen p200,
      phosphotransferase enzyme family protein, short chain dehydrogenase and 2
      hypothetical proteins. These immunogens were then transferred to an ELISA
      platform for further large scale screening. By combining shotgun expression
      library and ELISA assays, we identified 2 polypeptides BPSS1904 (benzoate 1,2
      dioxygenase beta subunit) and BPSL3130 (hypothetical protein), which had
      sensitivities of 78.9% and 79.4% and specificities of 88.1% and 94.8%,
      respectively in ELISA test, thus suggesting that both are potential candidate
      antigens for the serodiagnosis of infections caused by B. pseudomallei.

PMID- 23532807
TI  - Pain-related behaviour in children: a randomised study during two sequential
      dental visits.
AB  - AIM: To determine the difference in pain- and distress-related behaviour in
      children between two consecutive dental treatment sessions using a computer
      controlled local anaesthetic delivery system, with dental anxiety as co-variable.
      METHODS: A randomised prospective study over two sequential visits in three
      paediatric dental practices. For both visits 112 young, healthy children needing
      dental treatment were randomly assigned to either the use of the Wand((r)) or the
      Sleeper One((r)). All statistical analyses were performed using SPSS 17. A
      significance level of p < 0.01 was used, correcting for conducting a high number
      of tests. RESULTS: Children showed significantly more muscle tension, more verbal
      protest, and more crying or screaming during the second treatment. CONCLUSIONS:
      Sequential dental treatments seem to have a conditioning effect. It is important
      to know the level of dental anxiety to adjust the treatment sequence to the needs
      of the child.

PMID- 23532808
TI  - Comparison of two computerised anaesthesia delivery systems: pain and pain
      related behaviour in children during a dental injection.
AB  - AIM: The purpose of this study was to investigate whether there is a difference
      in pain and distress response of the child when using two different computer
      controlled local analgesic delivery systems, the Sleeper One((r)) and the
      WAND((r)), and whether this was influenced by the anxiety level of the child.
      METHODS: This randomised controlled trial was conducted among 112 children (56
      girls) aged 4-6 years (mean age 66 months, SD 9 months). All children needing at
      least one dental visit using local analgesia were randomly assigned to either the
      Sleeper One((r)) or the WAND((r)). RESULTS: During the injection phase, children
      expressed the same amount of disruptive behaviour using the Sleeper One((r)) or
      the WAND((r)) (Mann-Whitney U test, p > 0.05). The average injection time of the
      Sleeper One((r)) (mean 2.49 min, SD 0.56) was significantly shorter than that of
      the WAND((r)) (mean 3.20 min, SD 0.61; Mann-Whitney U test, p < 0.001).
      CONCLUSION: No significant difference was found in pain and distress reaction of
      the child between the WAND((r)) and the Sleeper One((r)). The average delivery
      time of the Sleeper One((r)) was shorter.

PMID- 23532809
TI  - Dental anxiety and dental pain in 5- to 12-year-old children in Recife, Brazil.
AB  - BACKGROUND: Dental anxiety is a common problem, related to dental pain, which
      contributes to irregular dental attendance and avoidance of dental care,
      resulting in poorer oral health during childhood. AIM: To evaluate anxiety, pain
      and/or discomfort related to dental treatment in 5- to 12-year-old children
      examined during a public holiday. METHODS: This cross-sectional survey study was
      carried out with parental permission in 970 children of both sexes. Socio
      economic status, dental anxiety and dental pain experience data were obtained
      through a questionnaire answered by parents or guardians. Dental anxiety was
      measured using the dental anxiety questionnaire (DAQ). The statistical analyses
      were performed using Pearson's Chi-square test. The intra-examiner agreement was
      high (kappa = 0.80) and the inter-examiner was kappa = 0.79. RESULTS: The
      prevalence of dental anxiety was 39.4 % and that of a history of dental pain was
      44.9 %. Dental anxiety among children was associated with the child never having
      had a dental appointment. STATISTICS: The anxiety correlated positively with a
      history of dental pain (p < 0.001), the mother's low level of schooling (p =
      0.037), parents' dental anxiety (p < 0.001), and negatively with visits to the
      dentist (p < 0.001). CONCLUSION: A high percentage of children presented with
      dental anxiety and a history of dental pain.

PMID- 23532810
TI  - The prevalence and associated risk factors for tooth wear and dental erosion in
      15- to 16-year-old schoolchildren in Amman, Jordan.
AB  - BACKGROUND: Tooth wear and acid erosion have not been previously investigated in
      Jordanian schoolchildren. AIM: To determine the prevalence of tooth wear and
      associations for a range of dietary and behavioural risk factors. METHODS: A
      sample of 1,602 children aged between 15 and 16 years were randomly selected from
      32 schools in Amman, Jordan. Tooth wear was measured using the modified Tooth
      Wear Index and dichotomised on the presence or absence of exposed dentine.
      Analysis of questionnaire items was performed by multiple logistic regression
      analysis. RESULTS: Dentine was exposed in 51 % of children, and males (59 %) had
      significantly more tooth wear than females (42 %), OR = 1.9, 95 % CI 1.6, 2.4, p
      < 0.0001. Over 40 % of children had dentine exposed occlusally, mainly the lower
      first molars, and less than 1 % of the children had dentine exposed palatally.
      Daily consumption of oranges, ketchup, olives and sweetened coffee was associated
      with tooth wear through enamel to expose dentine. Carbonated drinks (fizzy) were
      on the borderline of significance at p = 0.055. The mean DMFT (5.52) was
      significantly greater in children without tooth wear compared to children with
      tooth wear (4.13) (p < 0.001). DMFT, gender, daily consumption of oranges and
      daily consumption of ketchup were significantly associated with tooth wear in the
      multiple regression model. CONCLUSION: In this sample of children resident in
      Amman, Jordan, males had significantly more tooth wear than females. The acidic
      dietary items associated with tooth wear and, thus, dental erosion included
      oranges, olives and tomato ketchup.

PMID- 23532811
TI  - Registration of dental erosive wear on study models and intra-oral photographs.
AB  - BACKGROUND: Clinical photographs and study models may provide permanent records
      of dental erosion and be useful supplements to clinical registration. AIM: To
      assess the reliability and validity of registrations on clinical photographs and
      study models performed by a group of examiners. METHODS: Thirty tooth surfaces
      were selected and assessed clinically, using the visual erosion dental
      examination system. The chosen surfaces provided the whole range of dental
      erosions including sound surfaces. The tooth surfaces were photographed and
      impressions were obtained for preparation of study models. Thirty-three dentists
      examined and scored the selected surfaces both on photographs and study models.
      RESULTS: The quality of diagnosis (AUC, area under curve) was slightly higher
      using photographs as compared to study models. The difference was statistically
      significant when the validation criterion was erosion, assuming dentine exposure.
      The inter-method agreement on photographs and study models versus the clinical
      evaluation were approximately in the same range with a mean kappaw of 0.48 and
      0.43, respectively. When comparing study models with photographs the mean kappaw
      was 0.52. The intra-examiner agreement was strong/substantial for both
      (photographs mean kappaw = 0.63 and study models mean kappaw = 0.60). STATISTICS:
      Linear weighted Cohen's kappa (kappaw) was used to evaluate inter-method and
      intra-examiner agreement. Receiver operating characteristic and area under the
      curves were used to express diagnostic quality according to a clinical
      examination. CONCLUSION: The results indicated that photographs were as good as
      study models for recording erosive lesions.

PMID- 23532812
TI  - Pilot study of minimally invasive cast adhesive copings for early restoration of
      hypomineralised first permanent molars with post-eruptive breakdown.
AB  - BACKGROUND: Severely hypomineralised first permanent molars (FPMs) in children
      with molar incisor hypomineralisation (MIH) often require comprehensive
      restorative treatment. Different types of treatment have been described in the
      literature, including conservative treatment and use of various types of crowns.
      AIM: To describe a gentle and minimally invasive method for restoration of
      severely hypomineralised FPMs and to perform an initial, practice-based
      evaluation of the outcome for up to a 10-year follow-up period. METHODS: Thirty
      three children (mean age 12.1 years, SD 2.6) were treated with 57 minimally
      invasive cast adhesive gold copings (CAC). Sedation, local analgesia using a
      computer-controlled injection device, and behaviour management techniques were
      used to secure gentle care of the child. In cases with need for treatment of
      several teeth, the teeth not under treatment were covered by splints. The
      preparation border was placed in sound enamel, allowing 1/2-2 mm space to secure
      sufficient strength of the final restoration, which was cemented with dual
      composite cement. Follow-up examinations were performed by the dentists referring
      the children. RESULTS: All the children referred for treatment could be treated
      using this procedure, and of the 57 CAC, 56 (98.2 %) were still functioning after
      a mean observation period of 38.6 months (SD 28.9). CONCLUSION: In addition to
      existing types of treatment, minimally invasive CAC seems to be a feasible and
      useful method for restoration of FPMs with demarcated opacities and post-eruptive
      surface loss in children with MIH.

PMID- 23532813
TI  - Incidence and prevention of traumatic injuries in paediatric handball players in
      Istanbul, Turkey.
AB  - AIM: To investigate the frequency of dental injuries in paediatric handball
      players. In addition, the players' habits with regard to mouthguard usage, as
      well as their general knowledge of the prevention of traumatic dental injuries
      (TDIs) were investigated. Data were collected by structured one-to-one interviews
      with children of 14 randomly selected handball teams in the amateur national
      league. METHODS: The questionnaire consisted of 15 questions. The age, gender,
      trauma experience and league status of each interviewee was recorded. The
      interviews took place mainly at national championships or tournaments. RESULTS: A
      total of 212 individuals, 74 girls and 138 boys, were interviewed. Forty-one of
      the 212 participants (19.3 %) had sustained a dental injury. The mean age of
      participants was 12 +/- 1.6 years. Concussion was the most frequent finding and
      the cause of injury was a blow from another player. The number of individuals
      that were aware of mouthguards was only 15.6 % and surprisingly no players used
      mouthguards. CONCLUSIONS: The results show that handball players need more
      knowledge and education considering the prevention of TDIs from their sports
      clubs and dentists. The importance of adequate facial protection in contact
      sports should be endorsed by all sports clubs, and parents advised accordingly.

PMID- 23532814
TI  - 15-year follow-up of a case of amelogenesis imperfecta: importance of
      psychological aspect and impact on quality of life.
AB  - BACKGROUND: Amelogenesis imperfecta (AI) represents a group of hereditary
      conditions which affects enamel formation in the primary and permanent
      dentitions. Gene mutations alter the quality and/or quantity of enamel. AI often
      has severe consequences for the patient such as high tooth sensitivity, low
      aesthetic quality of the dentition, and poor mechanical properties of the dental
      tissues. This can result in reduced oral health-related quality of life. CASE
      REPORT: We present the case of a child affected by AI which had been diagnosed at
      the age of 9 years. Teeth presented many enamel defects. The patient presented
      thin brown to yellow enamel and the surface was rough and granular. He revealed
      short clinical crowns, occlusal wear with exposed dentine in posterior areas. He
      also presented a lateral open bite and lingual lateral interposition due to
      partial destruction of deciduous molars. Panoramic radiograph showed no
      differences between enamel and dentine appearance and also coronary destruction
      of permanent molars. TREATMENT: The initial treatment consisted of adaptation of
      composite resins on permanent incisors to improve aesthetics. Preformed metal
      crowns were placed on first permanent molars to prevent their premature
      destruction. FOLLOW-UP: This was disrupted for a variety of reasons. Fourteen
      years later, after a dental nomadism, the patient consulted by chance a dentist
      who identified his genetic pathology and was aware of its consequences. Extensive
      prosthodontic treatment was needed, but oral hygiene was poor and gingivitis
      remained. CONCLUSION: Dealing with high loss of motivation has been one of the
      main challenges because this patient had a lot of psychological problems. He was
      concerned, as are many patients affected by AI or other enamel abnormalities.
      This paper highlights the difficulties of long-term care of this dental
      abnormality. Psychological aspects of the quality of life, which is a common
      feature in patients suffering from many kinds of enamel anomalies, are very
      important.

PMID- 23532815
TI  - Expression of CD133 in acute leukemia.
AB  - There have been conflicting results regarding a correlation between CD133
      expression and disease outcome. To assess CD133 expression in patients with acute
      myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its
      correlation with the different clinical and laboratory data as well as its
      relation to disease outcome, the present study included 60 newly diagnosed acute
      leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their
      ages ranged from 9 months to 48 years, and 30 AML patients with a male to female
      ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric
      assessment of CD133 expression was performed on blast cells. In ALL, no
      correlations were elicited between CD133 expression and some monoclonal
      antibodies, but in AML group, there was a significant positive correlation
      between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients
      with negative CD133 expression achieved complete remission more than patients
      with positive CD133 expression. In AML group, there was no statistically
      significant association found between positive CD133 expression and treatment
      outcome. The Kaplan-Meier curve illustrated a high significant negative
      correlation between CD133 expression and the overall survival of the AML
      patients. CD133 expression is an independent prognostic factor in acute leukemia,
      especially ALL patients and its expression could characterize a group of acute
      leukemic patients with higher resistance to standard chemotherapy and relapse.
      CD133 expression was highly associated with poor prognosis in acute leukemic
      patients.

PMID- 23532816
TI  - Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and
      CEA.
AB  - CYFRA 21-1 and CEA have been applied for the differential diagnosis of malignant
      pleural mesothelioma (MPM). The soluble mesothelin-related peptide (SMRP) has
      been proposed as a specific marker for distinguishing MPM from benign diseases
      and other malignancies in pleural effusions (PEs). In this study, we evaluated
      the usefulness of SMRP in PEs in the detection of mesotheliomas by comparing it
      with that of CYFRA 21-1, CEA, and with cytological examination. One hundred and
      seventy-seven consecutive patients (57 MPM, 64 metastatic tumors, and 56 benign
      diseases) were evaluated using commercial tests. The performance of the markers
      was analyzed by standard ROC analysis methods, using the area under a ROC curve
      (AUC) as a measure of accuracy. CYFRA 21-1 better differentiated malignant from
      benign effusions. The corresponding area under the receiver operating
      characteristic curve was 0.87, while it was 0.74 for SMRP and 0.64 for CEA (p <
      0.001). Conversely, SMRP differentiated MPM from all other PEs better than both
      CYFRA 21-1 and CEA (AUC = 0.84, 0.76, and 0.32, respectively, p = 0.003). Low
      levels of CEA were associated with a MPM diagnosis. The AUC for differentiating
      MPM from metastases was 0.81 for SMRP, 0.61 for CYFRA 21-1, and 0.20 for CEA (p <
      0.001). In cases with negative or suspicious cytology, SMRP and CYFRA 21-1
      identified 36/71 and 46/66 malignant PEs (29 and 31 MPM, respectively). Only 1
      MPM showed a high CEA concentration. No single marker showed the best performance
      in any comparison. Results suggest that SMRP could improve CYFRA 21-1 and CEA
      accuracy in the differential diagnosis of MPM.

PMID- 23532817
TI  - Evidence for predictive role of BRCA1 and bTUBIII in gastric cancer.
AB  - Sensitivity of gastric cancer (GC) to conventional cytotoxic therapy may be at
      least in part attributed to molecular features of the tumor cells. We analyzed
      all patients with metastatic GC treated in the N.N. Petrov Institute of Oncology
      (St. Petersburg) within years 1999-2010 and identified 65 cases with evaluable
      treatment response and available biological material. Two of 65 patients (3 %)
      carried germ-line BRCA1 5382insC mutation and demonstrated particularly
      pronounced response to the treatment; both of their tumors showed loss of the
      remaining BRCA1 allele, thus confirming the causative role of BRCA1
      heterozygosity in GC predisposition. RNA expression of TS, DPD, BRCA1, ERCC,
      TOP2A and bTUBIII was analyzed in the remaining 63 tumors. Low BRCA1 expression
      was associated with increased response rate [6/9 (67 %) vs. 17/54 (32 %), p =
      0.04]. Low bTUBIII level correlated with the improved probability of tumor
      response [21/49 (43 %) vs. 1/13 (8 %), p = 0.02] and prolonged overall survival
      (10.5 vs. 7.1 months, p = 0.02); this trend was maintained both for taxane
      containing and for taxane-free drug combinations. We conclude that GC should be
      considered as a part of BRCA1-related hereditary cancer syndrome. Tumors with
      BRCA1 inactivation and low bTUBIII expression demonstrate improved response to
      cytotoxic therapy.

PMID- 23532818
TI  - MicroRNA-215 inhibits relapse of colorectal cancer patients following radical
      surgery.
AB  - To investigate the role of miR-215 in the relapse following radical surgery of
      colorectal cancer patients. The clinical data and surgical frozen tumor tissues
      were retrospectively collected from 125 stage II/III colorectal cancer patients,
      which contained 60 patients who relapsed and 65 patients who did not relapse
      within 3 years after surgery. The expression of miR-215 was determined by real
      time PCR, and the relationship between miR-215 expression and the relapse was
      analyzed statistically. miR-215 was downregulated in relapsed patients compared
      to nonrelapsed patients (P = 0.001). The low expression of miR-215 was
      significantly correlated with a high probability of 3-year relapse (P = 0.001),
      which was more obvious in stage III patients (P < 0.001). The multivariate
      analysis showed that miR-215 expression could function as an independent
      predictive marker for relapse. It seemed that patients with high expressions of
      miR-215 could benefit from 5-fluorouracil-containing adjuvant chemotherapy
      without significant difference, whereas this phenomenon was reverse in patients
      with low expressions of miR-215. Our study highlighted for the first time that
      miR-215 could function as a potential predictive marker for relapse following
      radical surgery of colorectal cancer, and the possible correlation between miR
      215 and 5-fluorouracil-containing adjuvant chemotherapy would be validated in the
      future.

PMID- 23532819
TI  - Functional Impact of Sydenham's Chorea: A Case Report.
AB  - BACKGROUND: Sydenham's chorea (SC) is the most common type of acquired chorea in
      childhood. In some cases, symptoms (most commonly described in terms of
      neurological signs) last up to 2 years, and many cases relapse. This report
      describes the clinical course in terms of functional abilities following
      diagnosis of SC. CASE REPORT: Standardized assessments across the domains of
      activity and participation were administered following diagnosis, prior to and
      following treatment with haloperidol to measure treatment response and identify
      occupational therapy intervention needs. SC was observed to significantly reduce
      the child's participation and independence in activities of daily living. In this
      case, the standardized assessments administered highlighted difficulties with
      both motor and process skills. At 1 week after commencing haloperidol, both motor
      and process skills had improved. Clinically significant changes in self-care and
      mobility were noted with less improvement with handwriting. At 9 weeks, most
      symptoms and functional difficulties had resolved. DISCUSSION: Given the process
      difficulties detected in this case, and the possibility of enduring symptoms, the
      use of functional assessments is advocated in the routine management of SC. These
      findings illustrate the potential for motor and non-motor sequelae in acute
      childhood movement disorders and related functional disabling consequences.

PMID- 23532820
TI  - Introducing the first issue in 2013 . Editorial.

PMID- 23532821
TI  - The level of knowledge of, attitude toward and emphasis given to HBV and HCV
      infections among healthcare professionals: data from a tertiary hospital in
      Turkey.
AB  - OBJECTIVES: To evaluate the level of knowledge of, to investigate the attitudes
      toward, and to determine the emphasis given to the national prevalence of HBV/HCV
      infections among healthcare professionals. MATERIALS AND METHODS: A total of 206
      healthcare professionals (mean (SD) age: 37.0 (6.3) years; 86.9% - females)
      including medical laboratory technicians (N = 54) and nurses (N = 152) employed
      in the Antalya Training and Research Hospital, Antalya, Turkey. Laboratory (N =
      53), operating room (N = 41) and in-patient clinic (N = 112) staff were included
      in this descriptive study. A 33-item questionnaire composed of questions related
      to their level of knowledge and attitudes toward HBV/HCV infections, the sources
      of their knowledge of HBV/HCV infections and the emphasis given to the national
      and global importance of the diseases was administered via a face-to-face
      interview method with each subject; participation was volunteer based. RESULTS:
      The participants working in the in-patient clinic (18.0 (3.2)) had the highest
      mean (SD) knowledge level compared to the laboratory (16.4 (3.1), p < 0.05) and
      operating room (17.0 (2.8), p < 0.05) staff. The participants from the in-patient
      clinic (44.6%) had a more advanced level of knowledge compared to the
      participants working in the laboratory (27.8%, p < 0.05) and the operating room
      (30.0%, p < 0.05). Most of the subjects (60.7%) had education concerning HBV/HCV
      infections in the past. There was no significant difference between the hospital
      units in terms of the attitudes of healthcare workers (HCWs) toward HBV/HCV
      infections and the level of education concerning them. CONCLUSIONS: Our findings
      revealed a moderate level of knowledge in most HCWs, regardless of their exposure
      to risk. While the highest knowledge scores and vaccination rates were noted
      among the in-patient clinic staff, there was no significant difference between
      the hospital units in terms of the attitudes of HCWs towards a patient or a
      colleague with an HBV/HCV infection.

PMID- 23532822
TI  - Gender differentiation of indirect self-destructiveness.
AB  - OBJECTIVES: The objective of this study was to examine the sex (gender)
      differentiation of indirect self-destructiveness intensity and its
      manifestations, as well as relationships between indirect self-destructiveness
      and its manifestations (categories) and the psychological dimensions of
      masculinity and femininity, also from the point of view of assessing occupational
      health and safety. MATERIALS AND METHODS: A population of 558 individuals (399
      females and 159 males) aged 19-25 (mean age: 22.6) was studied. The Polish
      version of the "Chronic Self-Destructiveness Scale" (CS-DS) by Kelley adapted by
      Suchanska was used in order to examine indirect self-destructiveness and its
      manifestations. Gender testing applied the Polish version of the Bem Sex Role
      Inventory (BSRI) by Bem in its adaptation by Kuczynska. RESULTS: Males' scores
      are significantly higher than those of females for the majority of CS-DS
      scales/indices: Indirect Self-Destructiveness (general index), Poor Health
      Maintenance (A2), Lack of Planfulness (A4), and Helplessness, Passiveness (A5).
      Moreover, there are statistically significant correlations between CS-DS scales
      and the masculinity dimension (positive) as well as the femininity dimension
      (negative). CONCLUSIONS: Masculinity is a factor that may predispose towards
      indirectly self-destructive behaviors, while femininity is a factor protecting
      against those. The study results may prove useful in preventing indirectly and
      directly self-destructive behaviors as well as in therapy work with the
      individuals who display such tendencies or have made attempts on their own lives,
      in particular taking into account their being of a specific sex/gender and in the
      context of work (especially in difficult or dangerous conditions or both).

PMID- 23532823
TI  - Electronic noses for monitoring benzene occupational exposure in biological
      samples of Egyptian workers.
AB  - OBJECTIVES: Benzene is commonly emitted in several industries, leading to
      widespread environmental and occupational exposure hazards. While less toxic
      solvents have been substituted for benzene, it is still a component of petroleum
      products and is a trace impurity in industrial products resulting in continued
      higher occupational exposures in industrial settings in developing countries.
      MATERIALS AND METHODS: We investigated the potential use of an electronic nose (e
      nose) to monitor the headspace volatiles in biological samples from benzene
      exposed Egyptian workers and non-exposed controls. The study population comprised
      150 non-smoking male workers exposed to benzene and an equal number of matching
      non-exposed controls. We determined biomarkers of benzene used to estimate
      exposure and risk including: benzene in exhaled air and blood; and its urinary
      metabolites such as phenol and muconic acid using gas chromatography technique
      and a portable e-nose. RESULTS: The average benzene concentration measured in the
      ambient air of the workplace of all studied industrial settings in Alexandria,
      Egypt; was 97.56 +/- 88.12 MUg/m(3) (range: 4.69-260.86 MUg/m(3)). Levels of
      phenol and muconic acid were significantly (p < 0.001) higher in both blood and
      urine of benzene-exposed workers as compared to non-exposed controls.
      CONCLUSIONS: The e-nose technology has successfully classified and distinguished
      benzene-exposed workers from non-exposed controls for all measured samples of
      blood, urine and the exhaled air with a very high degree of precision. Thus, it
      will be a very useful tool for the low-cost mass screening and early detection of
      health hazards associated with the exposure to benzene in the industry.

PMID- 23532824
TI  - Observance of hand washing procedures performed by the medical personnel before
      patient contact. Part I.
AB  - INTRODUCTION: According to the Centers for Disease Control and Prevention (CDC)
      as well as the World Health Organization (WHO) recommendations, medical staff are
      obliged to decontaminate the skin of the hands before every single patient
      contact. MATERIALS AND METHODS: The study was performed by quasi-observation
      among the group of 188 medical staff (nurses and physicians) working in three
      selected hospitals of the Lodz province. The procedure of hand washing and
      disinfection performed directly before the patient contact according to the CDC
      and WHO recommendations were observed. The results was subject to statistical
      analysis (p < 0.05). RESULTS: During 1544 hours of observation 4101 activities
      requiring hand washing were recorded. The medical staff obeyed the hand washing
      procedure before the patient contact only in 5.2% of the situations. There was no
      activity observed before which hand hygiene was maintained in 100% of cases.
      Observance of hand hygiene depended significantly on the type of the performed
      activity, the professional group, and the workload index. A decrease in
      percentage observance of hand hygiene according to the time of the day was found
      to be of statistical significance. The mean time of hand washing was 8.5 s for
      physicians and 6.6 s for nurses. CONCLUSION: The level of observance of hand
      washing procedures among the medical staff prior to the patient contact appears
      to be alarmingly below the expectations.

PMID- 23532825
TI  - Specific removal of TACC3-ch-TOG-clathrin at metaphase deregulates kinetochore
      fiber tension.
AB  - Microtubule-associated proteins of the mitotic spindle are thought to be
      important for the initial assembly and the maintenance of spindle structure and
      function. However, distinguishing assembly and maintenance roles for a given
      protein is difficult. Most experimental methods for protein inactivation are slow
      and therefore affect both assembly and maintenance. Here, we have used
      'knocksideways' to rapidly (~5 minutes) and specifically remove TACC3-ch-TOG
      clathrin non-motor complexes from kinetochore fibers (K-fibers). This method
      allows the complex to be inactivated at defined stages of mitosis. Removal of
      TACC3-ch-TOG-clathrin after nuclear envelope breakdown caused severe delays in
      chromosome alignment. Inactivation at metaphase, following a normal prometaphase,
      significantly delayed progression to anaphase. In these cells, K-fiber tension
      was reduced and the spindle checkpoint was not satisfied. Surprisingly, there was
      no significant loss of K-fiber microtubules, even after prolonged removal. TACC3
      ch-TOG-clathrin removal during metaphase also resulted in a decrease in spindle
      length and significant alteration in kinetochore dynamics. Our results indicate
      that TACC3-ch-TOG-clathrin complexes are important for the maintenance of spindle
      structure and function as well as for initial spindle assembly.

PMID- 23532827
TI  - Ruthenium-catalyzed asymmetric transfer hydrogenation of 1-aryl-substituted
      dihydroisoquinolines: access to valuable chiral 1-aryl-tetrahydroisoquinoline
      scaffolds.

PMID- 23532826
TI  - Transcriptome Profiling Identifies Candidate Genes Associated with the
      Accumulation of Distinct Sulfur gamma-Glutamyl Dipeptides in Phaseolus vulgaris
      and Vigna mungo Seeds.
AB  - Common bean (Phaseolus vulgaris) and black gram (Vigna mungo) accumulate gamma
      Glutamyl-S-methylcysteine and gamma-Glutamyl-methionine in seed, respectively.
      Transcripts were profiled by 454 pyrosequencing data at a similar developmental
      stage coinciding with the beginning of the accumulation of these metabolites.
      Expressed sequence tags were assembled into Unigenes, which were assigned to
      specific genes in the early release chromosomal assembly of the P. vulgaris
      genome. Genes involved in multiple sulfur metabolic processes were expressed in
      both species. Expression of Sultr3 members was predominant in P. vulgaris,
      whereas expression of Sultr5 members predominated in V. mungo. Expression of the
      cytosolic SERAT1;1 and -1;2 was approximately fourfold higher in P. vulgaris
      while expression of the plastidic SERAT2;1 was twofold higher in V. mungo. Among
      BSAS family members, BSAS4;1, encoding a cytosolic cysteine desulfhydrase, and
      BSAS1;1, encoding a cytosolic O-acetylserine sulphydrylase were most highly
      expressed in both species. This was followed by BSAS3;1 encoding a plastidic beta
      cyanoalanine synthase which was more highly expressed by 10-fold in P. vulgaris.
      The data identify BSAS3;1 as a candidate enzyme for the biosynthesis of S
      methylcysteine through the use of methanethiol as substrate instead of cyanide.
      Expression of GLC1 would provide a complete sequence leading to the biosynthesis
      of gamma-Glutamyl-S-methylcysteine in plastids. The detection of S
      methylhomoglutathione in P. vulgaris suggested that homoglutathione synthetase
      may accept, to some extent, gamma-Glutamyl-S-methylcysteine as substrate, which
      might lead to the formation of S-methylated phytochelatins. In conclusion, 454
      sequencing was effective at revealing differences in the expression of sulfur
      metabolic genes, providing information on candidate genes for the biosynthesis of
      distinct sulfur amino acid gamma-Glutamyl dipeptides between P. vulgaris and V.
      mungo.

PMID- 23532828
TI  - In Vitro Synergy of Telavancin and Rifampin Against Enterococcus faecium
      Resistant to Both Linezolid and Vancomycin.
AB  - BACKGROUND: An emerging pathogen is Enterococcus faecium resistant to both
      linezolid and vancomycin (LRVRE). Antimicrobial combinations may be required for
      therapy and need to be evaluated. The combination of daptomycin and rifampin has
      demonstrated good in vitro activity against gram-positive bacteria, including E
      faecium. Telavancin, a newer lipoglycopeptide, has shown in vitro activity
      against E faecium. We evaluated the combination of telavancin and rifampin and
      compared the results to the combination of daptomycin and rifampin used
      previously on the same isolates. METHODS: Twenty-four genetically unique (by
      pulsed-field gel electrophoresis), clinical LRVRE isolates were collected in the
      United States from 2001-2004. Etest minimal inhibitory concentrations (MICs)
      (MUg/mL) were 0.064-8 for telavancin, 1-4 for daptomycin, and 0.012 to >32 for
      rifampin. In vitro synergy testing was performed in triplicate by an Etest
      MIC:MIC ratio method, and summation fractional inhibitory concentration
      (SigmaFIC) was calculated: synergy <=0.5; indifference >0.5-4; and antagonism >4.
      RESULTS: The Etest method showed synergy (SigmaFICs of 0.1-0.5) with telavancin +
      rifampin in 20/24 (83%) isolates and indifference (SigmaFICs of 0.6-0.8) in 4/24
      (17%) isolates. Similarly, the daptomycin + rifampin combination showed synergy
      (SigmaFICs of 0.1-0.5) in 21/24 (88%) isolates and indifference (SigmaFICs of 0.6
      1.0) in 3/24 (12%) isolates by the Etest method. No antagonism was found.
      CONCLUSIONS: In vitro synergy with both combinations (rifampin + telavancin or
      daptomycin) was 83% and 88%, respectively, by Etest against these LRVRE isolates.
      Although both daptomycin and telavancin in combination with rifampin showed a
      high incidence of synergistic activity, further in vitro synergy testing with
      this combination should be performed against additional E faecium isolates. In
      vitro synergy may or may not translate into in vivo effectiveness.

PMID- 23532829
TI  - Evidence for Genetic Reassortment between Human Rotaviruses by Full Genome
      Sequencing of G3P[4] and G2P[4] Strains Co-circulating in India.
AB  - Rotavirus A causes severe diarrhoea in infants and young children worldwide. Many
      unusual combinations of G and P genotypes have been observed in rotaviruses
      circulating in developing countries. Mixed infection of a single individual with
      more than one strain is a mechanism by which genetic reassortants are formed with
      unusual G and P combinations. However, few studies have provided direct evidence
      for the formation of such unusual strains as a result of co-infection of co
      circulating strains. Here, we used full-genome sequencing to re-analyze a G3P[4]
      strain (107E1B) and a G2P[4] strain (116E3D) detected in India in 1993 and showed
      that 107E1B had virtually an identical nucleotide sequence with 116E3D, except
      the VP7 gene. Phylogenetic analysis revealed that the 107E1B VP7 gene was of
      typical human rotavirus origin, with a 99.3% nucleotide sequence identity with
      another Indian G3 VP7 gene. Thus, this study provided robust evidence for the
      formation of the G3P[4] strain through genetic reassortment in which a G2P[4]
      strain with a typical DS-1 genogroup background acquired the VP7 gene from a co
      circulating G3 human rotavirus strain. This study established a basis on which to
      facilitate full genome sequence analysis of an increasing number of G3P[4]
      strains in China and elsewhere in the world.

PMID- 23532830
TI  - Feasibility of use of a barbed suture (v-loc 180) for quilting the donor site in
      latissimus dorsi myocutaneous flap breast reconstruction.
AB  - BACKGROUND: Latissimus dorsi (LD) myocutaneous flap is a popular method of breast
      reconstruction which can be associated with high incidence of seroma formation.
      Quilting sutures at the harvest site are used to reduce this. Barbed sutures are
      self anchoring sutures which avoid multiple knotting and can be useful in
      quilting. METHODS: A retrospective analysis of prospectively maintained database
      of patients who underwent LD flap breast reconstruction between January 2009 and
      January 2011 was carried out. Seroma formation at the harvest site, wound related
      complications, inpatient stay and duration of surgery were analysed and a
      comparison was made between two groups where quilting was done with barbed (V
      Loc) suture and conventional polydioxanone (PDS) II sutures. RESULTS: Fifty-seven
      patients were included of which 33 had quilting by V-Loc sutures and in 24
      patients PDS II suture was used. Median age in the PDS group was 55 years
      (interquartile range [IQR)], 45 to 61 years) which was comparable to the V-Loc
      group (53 years [IQR, 48 to 59 years]; P-value 0.948). Sixteen patients (28%) had
      significant seroma formation and 5 (9%) patients developed superficial wound
      dehiscence. Incidences of seroma or wound complications were comparable (P-value
      0.378 and 1.00, respectively). Secondary outcomes such as total duration of
      surgery, total inpatient stay, total amount of drain at the donor site were also
      similar in two groups. CONCLUSIONS: Use of barbed sutures for quilting the donor
      site in LD flap reconstruction is a feasible option and the associated seroma
      formation and wound complications are comparable with conventional sutures.

PMID- 23532831
TI  - Lynch syndrome: the patients' perspective.
AB  - People with Lynch syndrome have a high lifetime risk for the development of
      colorectal, endometrial and several other types of cancer. Lynch syndrome is
      caused by germline mutations in genes encoding DNA mismatch repair proteins. In
      this review, issues that concern Lynch patients are highlighted from the
      patients' perspective. Both authors are affected by Lynch syndrome and are active
      in Lynch patient organizations. The goal of this review is to assist heath care
      providers in the improvement of care for individuals who share our disorder.
      Institutional and/or national guidelines that should lead to the identification
      of Lynch patients have been developed in many countries. However, adherence to
      these guidelines is poor and the consequence is severe underdiagnosis of Lynch
      syndrome. An important task of patient organizations is therefore to increase
      awareness of Lynch syndrome among the general public and health care providers.
      Because diagnosis of Lynch syndrome based on family history is difficult, the use
      of molecular and or histological techniques that permit unequivocal diagnosis
      should be more aggressively promoted. Since Lynch syndrome encompasses a broad
      spectrum of cancers, a multidisciplinary treatment and screening protocol for all
      Lynch patients is necessary. Lynch patients must be seen by a team of specialists
      that are knowledgeable in the various manifestations of Lynch syndrome. Because
      tumors with mismatch repair deficiency have specific properties, identification
      of effective chemotherapy regimens, specifically targeted to patients with
      deficiencies in DNA repair mechanisms, must be developed. The high lifetime risk
      of developing cancer in Lynch patients warrants lifestyle advice and research
      into chemopreventive measures that reduce the risk of cancer in this vulnerable
      group. Implementation of these recommendations will result in greatly improved
      quality of life for people affected with Lynch syndrome, it is therefore
      important that health care providers and patient organizations work together to
      achieve these goals. 

PMID- 23532832
TI  - Can the combination of ALSFRS and survival time analysis impact the outcome in
      phase III ALS clinical trials?

PMID- 23532833
TI  - Development of a novel electrochemical system for oxygen control (ESOC) to
      examine dissolved oxygen inhibition on algal activity.
AB  - The development of an Electrochemical System for Oxygen Control (ESOC) for
      examining algal photosynthetic activity as a function of dissolved oxygen (DO) is
      outlined. The main innovation of the tool is coulombic titration in order to
      balance the electrochemical reduction of oxygen with the oxygen input to achieve
      a steady DO set-point. ESOC allows quantification of algal oxygen production
      whilst simultaneously maintaining a desired DO concentration. The tool was
      validated abiotically by comparison with a mass transfer approach for quantifying
      oxygenation. It was then applied to quantify oxygen inhibition of algal activity.
      Five experiments, using an enriched culture of Scenedesmus sp. as the inoculum,
      are presented. For each experiment, ESOC was used to quantify algal activity at a
      series of DO set-points. In all experiments substantial oxygen inhibition was
      observed at DO >30 mgO2 L-1. Inhibition was shown to fit a Hill inhibition model,
      with a common Hill coefficient of 0.22+/-0.07 L mg-1 and common log10  CI50 of
      27.2+/-0.7 mg L-1. This is the first time that the oxygen inhibition kinetic
      parameters have been quantified under controlled DO conditions.

PMID- 23532834
TI  - Synthesis of new vasotocin analogues: effects on renal water and ion excretion in
      rats.
AB  - Vasopressin and nonmammalian hormone vasotocin are known to increase the water
      permeability of mammalian collecting ducts, frog skin and the urinary bladder.
      Neurohypophysial nonapeptides have also been shown to interfere with the
      regulation of renal ion transport. The subject of this study was a search for
      vasopressin and vasotocin analogues with selective effects on renal water, sodium
      and potassium excretion. During this study, we synthesised the following
      peptides: 13 vasotocin analogues modified at positions 4 (Thr or Arg), 7 (Gly or
      Leu) and 8 (D-Arg, Lys or Glu); 4 vasopressin analogues modified at positions 4
      and 8; and 9 peptides shortened or extended at the C-terminal or with
      substitutions for Gly-NH2. Most of these peptides had mercaptopropionic acid
      (Mpa) instead of Cys in position 1. The effects of these nonapeptides on renal
      water, sodium and potassium transport were evaluated in in vivo experiments using
      Wistar rats. Some nonapeptides possessed antidiuretic, natriuretic and kaliuretic
      activities ([Mpa(1)]-arginine vasotocin, [Mpa(1), homoArg(8)]-vasotocin, [Mpa(1),
      Thr(4)]-arginine vasotocin and [Mpa(1), Arg(4)]-arginine vasopressin).
      Substitutions at positions 4 and 8 increased the selectivity of peptide actions.
      The antidiuretic [D-Arg(8)]-vasotocin analogues had no effects on sodium
      excretion. [Mpa(1), Arg(4)]-arginine vasotocin was antidiuretic and kaliuretic
      but not natriuretic. [Mpa(1), Glu(8)]-oxytocin had weak natriuretic activity
      without any effects on water and potassium transport. In accordance with the data
      obtained, synthesised vasotocin analogues could be good candidates for
      pharmaceuticals selectively regulating renal sodium and potassium transport,
      which is of clinical importance.

PMID- 23532835
TI  - Existential behavioural therapy for informal caregivers of palliative patients: a
      randomised controlled trial.
AB  - BACKGROUND: Existential behavioural therapy (EBT) was developed to support
      informal caregivers of palliative patients in the last stage of life and during
      bereavement as a manualised group psychotherapy comprising six sessions. We
      tested the effectiveness of EBT on mental stress and quality of life (QOL).
      METHODS: Informal caregivers were randomly assigned (1:1) to EBT or a treatment
      as-usual control group using computer-generated numbers in blocks of 10. Primary
      outcomes were assessed with the Brief Symptom Inventory (subscales somatisation,
      anxiety and depression), the Satisfaction with Life Scale (SWLS), the WHOQOL-BREF
      and a numeric rating scale for QOL (QOL-NRS, range 0-10). Data were collected at
      baseline, pre-treatment, post-treatment and follow-ups after 3 and 12 months.
      Treatment effects were assessed with a multivariate analysis of covariance.
      RESULTS: Out of 160 relatives, 81 were assigned to EBT and 79 to the control
      group. Participants were 54.5 +/- 13.2 years old; 69.9% were female. The
      multivariate model was significant for the pre-/post-comparison (p=0.005) and the
      pre-/12-month comparison (p=0.05) but not for the pre-/3-month comparison. Medium
      to large effects on anxiety and QOL (SWLS, WHOQOL-BREF, QOL-NRS) were found at
      post-treatment; medium effects on depression and QOL (QOL-NRS) emerged in the 12
      month follow-up. No adverse effects of the intervention were observed.
      CONCLUSION: Existential behavioural therapy appears to exert beneficial effects
      on distress and QOL of informal caregivers of palliative patients. Further
      longitudinal evidence is needed to confirm these findings.

PMID- 23532836
TI  - Obesity-induced diabetes and lower urinary tract fibrosis promote urinary voiding
      dysfunction in a mouse model.
AB  - BACKGROUND: Progressive aging- and inflammation-associated fibrosis effectively
      remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and
      reduce urethral flexibility, resulting in urinary flow obstruction and lower
      urinary tract symptoms (LUTS). In the current study, we sought to test whether
      senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop
      prostatic fibrosis, would also develop LUTS, and whether these symptoms would be
      exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus
      (T2DM). METHODS: To accomplish this, SAMP6 and AKR/J background strain mice were
      fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months,
      then subjected to glucose tolerance tests, assessed for plasma insulin levels,
      evaluated for urinary voiding function, and assessed for lower urinary tract
      fibrosis. RESULTS: The results of these studies show that SAMP6 mice and AKR/J
      background strain mice develop diet-induced obesity and T2DM concurrent with
      urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more
      severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and
      urethral tissue fibrosis. CONCLUSIONS: Taken together, these studies suggest that
      obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are
      inextricably and biologically linked.

PMID- 23532837
TI  - Fatal occupational injuries among U.S. law enforcement officers: a comparison of
      national surveillance systems.
AB  - BACKGROUND: This study describes and compares the three surveillance systems used
      to record occupational injury fatalities among U.S. law enforcement officers
      (LEOs). METHODS: The Census of Fatal Occupational Injuries (CFOI), National Law
      Enforcement Officer Memorial Fund database (NLEOMF), and Law Enforcement Officers
      Killed and Assaulted reports (LEOKA) were examined for LEO deaths between 2003
      and 2009. Fatality rates per 100,000 workers were calculated and compared.
      RESULTS: Between 2003 and 2009, the NLEOMF reported 1,050 fatalities (rate of
      16.4 per 100,000 workers), the CFOI reported 968 fatalities (15.1 per 100,000),
      and the LEOKA recorded 853 fatalities (13.3 per 100,000). The LEOKA under-counted
      the number of fatalities compared to the NLEOMF and CFOI. Discrepancies were
      found between the LEOKA, NLEOMF, and CFOI regarding age, race, and Hispanic
      origin. Similar patterns for cause of fatality were found; however, the NLEOMF
      recorded a higher number of "other" fatalities compared to the other two systems.
      CONCLUSIONS: This study fills a critical knowledge gap by providing an overview
      of the three surveillance systems used to enumerate LEO occupational deaths.
      Understanding the differences across the systems is critical when utilizing them
      for surveillance research.

PMID- 23532838
TI  - Structure and activity of the flagellar rotor protein FliY: a member of the CheC
      phosphatase family.
AB  - BACKGROUND: FliY is a flagellar rotor protein of the CheC phosphatase family.
      RESULTS: The FliY structure resembles that of the rotor protein FliM but contains
      two active centers for CheY dephosphorylation. CONCLUSION: FliY incorporates
      properties of the FliM/FliN rotor proteins and the CheC/CheX phosphatases to
      serve multiple functions in the flagellar switch. SIGNIFICANCE: FliY
      distinguishes flagellar architecture and function in different types of bacteria.
      Rotating flagella propel bacteria toward favorable environments. Sense of
      rotation is determined by the intracellular response regulator CheY, which when
      phosphorylated (CheY-P) interacts directly with the flagellar motor. In many
      different types of bacteria, the CheC/CheX/FliY (CXY) family of phosphatases
      terminates the CheY-P signal. Unlike CheC and CheX, FliY is localized in the
      flagellar switch complex, which also contains the stator-coupling protein FliG
      and the target of CheY-P, FliM. The 2.5 A resolution crystal structure of the
      FliY catalytic domain from Thermotoga maritima bears strong resemblance to the
      middle domain of FliM. Regions of FliM that mediate contacts within the rotor
      compose the phosphatase active sites in FliY. Despite the similarity between FliY
      and FliM, FliY does not bind FliG and thus is unlikely to be a substitute for
      FliM in the center of the switch complex. Solution studies indicate that FliY
      dimerizes through its C-terminal domains, which resemble the Escherichia coli
      switch complex component FliN. FliY differs topologically from the E. coli
      chemotaxis phosphatase CheZ but appears to utilize similar structural motifs for
      CheY dephosphorylation in close analogy to CheX. Recognition properties and
      phosphatase activities of site-directed mutants identify two pseudosymmetric
      active sites in FliY (Glu(35)/Asn(38) and Glu(132)/Asn(135)), with the second
      site (Glu(132)/Asn(135)) being more active. A putative N-terminal CheY binding
      domain conserved with FliM is not required for binding CheY-P or phosphatase
      activity.

PMID- 23532839
TI  - Calcium-dependent phospholipid scramblase activity of TMEM16 protein family
      members.
AB  - BACKGROUND: TMEM16A and 16B work as Cl(-) channel, whereas 16F works as
      phospholipid scramblase. The function of other TMEM16 members is unknown.
      RESULTS: Using TMEM16F(-/-) cells, TMEM16C, 16D, 16F, 16G, and 16J were shown to
      be lipid scramblases. CONCLUSION: Some TMEM16 members are divided into two Cl(-)
      channels and five lipid scramblases. SIGNIFICANCE: Learning the biochemical
      function ofTMEM16family members is essential to understand their physiological
      role. Asymmetrical distribution of phospholipids between the inner and outer
      plasma membrane leaflets is disrupted in various biological processes. We
      recently identified TMEM16F, an eight-transmembrane protein, as a Ca(2+)
      dependent phospholipid scramblase that exposes phosphatidylserine (PS) to the
      cell surface. In this study, we established a mouse lymphocyte cell line with a
      floxed allele in the TMEM16F gene. When TMEM16F was deleted, these cells failed
      to expose PS in response to Ca(2+) ionophore, but PS exposure was elicited by Fas
      ligand treatment. We expressed other TMEM16 proteins in the TMEM16F(-/-) cells
      and found that not only TMEM16F, but also 16C, 16D, 16G, and 16J work as lipid
      scramblases with different preference to lipid substrates. On the other hand, a
      patch clamp analysis in 293T cells indicated that TMEM16A and 16B, but not other
      family members, acted as Ca(2+)-dependent Cl(-) channels. These results indicated
      that among 10 TMEM16 family members, 7 members could be divided into two
      subfamilies, Ca(2+)-dependent Cl(-) channels (16A and 16B) and Ca(2+)-dependent
      lipid scramblases (16C, 16D, 16F, 16G, and 16J).

PMID- 23532840
TI  - The alpha-helical structure of prodomains promotes translocation of intrinsically
      disordered neuropeptide hormones into the endoplasmic reticulum.
AB  - Different neuropeptide hormones, which are either too small to adopt a stable
      conformation or are predicted to be intrinsically disordered, are synthesized as
      larger precursors containing a prodomain in addition to an N-terminal signal
      peptide. We analyzed the biogenesis of three unstructured neuropeptide hormones
      and observed that translocation of these precursors into the lumen of the
      endoplasmic reticulum (ER) is critically dependent on the presence of the
      prodomain. The hormone domains could be deleted from the precursors without
      interfering with ER import and secretion, whereas constructs lacking the
      prodomain remained in the cytosol. Domain-swapping experiments revealed that the
      activity of the prodomains to promote productive ER import resides in their
      ability to adopt an alpha-helical structure. Removal of the prodomain from the
      precursor did not interfere with co-translational targeting of the nascent chain
      to the Sec61 translocon but with its subsequent productive translocation into the
      ER lumen. Our study reveals a novel function of prodomains to enable import of
      small or intrinsically disordered secretory proteins into the ER based on their
      ability to adopt an alpha-helical conformation.

PMID- 23532841
TI  - Lewy body-like alpha-synuclein aggregates resist degradation and impair
      macroautophagy.
AB  - Cytoplasmic alpha-synuclein (alpha-syn) aggregates, referred to as Lewy bodies,
      are pathological hallmarks of a number of neurodegenerative diseases, most
      notably Parkinson disease. Activation of macroautophagy is suggested to
      facilitate degradation of certain proteinaceous inclusions, but it is unclear if
      this pathway is capable of degrading alpha-syn aggregates. Here, we examined this
      issue by utilizing cellular models in which intracellular Lewy body-like alpha
      syn inclusions accumulate after internalization of pre-formed alpha-syn fibrils
      into alpha-syn-expressing HEK293 cells or cultured primary neurons. We
      demonstrate that alpha-syn inclusions cannot be effectively degraded, even though
      they co-localize with essential components of both the autophagic and proteasomal
      protein degradation pathways. The alpha-syn aggregates persist even after soluble
      alpha-syn levels have been substantially reduced, suggesting that once formed,
      the alpha-syn inclusions are refractory to clearance. Importantly, we also find
      that alpha-syn aggregates impair overall macroautophagy by reducing autophagosome
      clearance, which may contribute to the increased cell death that is observed in
      aggregate-bearing cells.

PMID- 23532842
TI  - Investigation of in vivo roles of the C-terminal tails of the small subunit
      (betabeta') of Saccharomyces cerevisiae ribonucleotide reductase: contribution to
      cofactor formation and intersubunit association within the active holoenzyme.
AB  - The small subunit (beta2) of class Ia ribonucleotide reductase (RNR) houses a
      diferric tyrosyl cofactor (Fe2(III)-Y(*)) that initiates nucleotide reduction in
      the large subunit (alpha2) via a long range radical transfer (RT) pathway in the
      holo-(alpha2)m(beta2)n complex. The C-terminal tails of beta2 are predominantly
      responsible for interaction with alpha2, with a conserved tyrosine residue in the
      tail (Tyr(356) in Escherichia coli NrdB) proposed to participate in cofactor
      assembly/maintenance and in RT. In the absence of structure of any holo-RNR, the
      role of the beta tail in cluster assembly/maintenance and its predisposition
      within the holo-complex have remained unknown. In this study, we have taken
      advantage of the unusual heterodimeric nature of the Saccharomyces cerevisiae RNR
      small subunit (betabeta'), of which only beta contains a cofactor, to address
      both of these issues. We demonstrate that neither beta-Tyr(376) nor beta'
      Tyr(323) (Tyr(356) equivalent in NrdB) is required for cofactor assembly in vivo,
      in contrast to the previously proposed mechanism for E. coli cofactor maintenance
      and assembly in vitro. Furthermore, studies with reconstituted-betabeta' and an
      in vivo viability assay show that beta-Tyr(376) is essential for RT, whereas
      Tyr(323) in beta' is not. Although the C-terminal tail of beta' is dispensable
      for cofactor formation and RT, it is essential for interactions with beta and
      alpha to form the active holo-RNR. Together the results provide the first
      evidence of a directed orientation of the beta and beta' C-terminal tails
      relative to alpha within the holoenzyme consistent with a docking model of the
      two subunits and argue against RT across the beta beta' interface.

PMID- 23532843
TI  - The tryptophan residue at the active site tunnel entrance of Trichoderma reesei
      cellobiohydrolase Cel7A is important for initiation of degradation of crystalline
      cellulose.
AB  - BACKGROUND: Mutation of Trp-40 in the Cel7A cellobiohydrolase from Trichoderma
      reesei (TrCel7A) causes a loss of crystalline cellulose-degrading ability.
      RESULTS: Mutant W40A showed reduced specific activity for crystalline cellulose
      and diffused the cellulose chain from the entrance of the active site tunnel.
      CONCLUSION: Trp-40 is essential for chain end loading to initiate processive
      hydrolysis of TrCel7A. SIGNIFICANCE: The mechanisms of crystalline polysaccharide
      degradation are clarified. The glycoside hydrolase family 7 cellobiohydrolase
      Cel7A from Trichoderma reesei is one of the best studied cellulases with the
      ability to degrade highly crystalline cellulose. The catalytic domain and the
      cellulose-binding domain (CBD) are both necessary for full activity on
      crystalline substrates. Our previous high-speed atomic force microscopy studies
      showed that mutation of Trp-40 at the entrance of the catalytic tunnel
      drastically decreases the ability to degrade crystalline cellulose. Here, we
      examined the activities of the WT enzyme and mutant W40A (with and without the
      CBD) for various substrates. Evaluation and comparison of the specific activities
      of the enzymes (WT, W40A, and the corresponding catalytic subunits (WTcat and
      W40Acat)) adsorbed on crystalline cellulose indicated that Trp-40 is involved in
      recruiting individual substrate chains into the active site tunnel to initiate
      processive hydrolysis. This was supported by molecular dynamics simulation study,
      i.e. the reducing end glucose unit was effectively loaded into the active site of
      WTcat, but not into that of W40Acat, when the simulation was started from subsite
      -7. However, when similar simulations were carried out starting from subsite -5,
      both enzymes held the substrate for 50 ns, indicating that the major difference
      between WTcat and W40Acat is the length of the free chain end of the substrate
      required to allow initiation of processive movements; this also reflects the
      difference between crystalline and amorphous celluloses. The CBD is important for
      enhancing the enzyme population on crystalline substrate, but it also decreases
      the specific activity of the adsorbed enzyme, possibly by attaching the enzyme to
      non-optimal places on the cellulose surface and/or hindering processive
      hydrolysis.

PMID- 23532845
TI  - Multiple exoribonucleases catalyze maturation of the 3' terminus of 16S ribosomal
      RNA (rRNA).
AB  - Processing of ribosomal RNA (rRNA) precursors is an important component of RNA
      metabolism in all cells. However, in no system have we yet identified all the
      RNases involved in this process. Here, we show that four 3'->5'-exoribonucleases,
      RNases II, R, and PH, and polynucleotide phosphorylase (PNPase), participate in
      maturation of the 3' end of 16S rRNA. In their absence, 16S precursor molecules
      with 33 extra 3'-nt accumulate; however, the presence of any one of the four
      RNases is sufficient to allow processing to occur, although with different
      efficiencies. Additionally, we find that in the absence of 3' maturation, 5'
      processing proceeds much less efficiently. Moreover, mutant 30S particles,
      containing immature 16S rRNA, form 70S ribosomes very poorly. These findings,
      together with the earlier discovery that RNases E and G are the 5'-processing
      enzymes, completes the catalogue of RNases involved in maturation of Escherichia
      coli 16S rRNA.

PMID- 23532844
TI  - The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper
      integration site 1 (AHI1) protein alters its localization and protein-protein
      interactions.
AB  - BACKGROUND: Missense mutations in AHI1 result in the neurodevelopmental
      ciliopathy called Joubert syndrome. RESULTS: Mutations in AHI1 decrease cilia
      formation, alter its localization and stability, and change its binding to HAP1
      and NPHP1. CONCLUSION: Mutations in AHI1 affect ciliogenesis, AHI1 protein
      localization, and AHI1-protein interactions. SIGNIFICANCE: This study begins to
      describe how missense mutations in AHI1 can cause Joubert syndrome. Mutations in
      AHI1 cause Joubert syndrome (JBTS), a neurodevelopmental ciliopathy,
      characterized by midbrain-hindbrain malformations and motor/cognitive deficits.
      Here, we show that primary cilia (PC) formation is decreased in fibroblasts from
      individuals with JBTS and AHI1 mutations. Most missense mutations in AHI1,
      causing JBTS, occur in known protein domains, however, a common V443D mutation in
      AHI1 is found in a region with no known protein motifs. We show that cells
      transfected with AHI1-V443D, or a new JBTS-causing mutation, AHI1-R351L, have
      aberrant localization of AHI1 at the basal bodies of PC and at cell-cell
      junctions, likely through decreased binding of mutant AHI1 to NPHP1 (another JBTS
      causing protein). The AHI1-V443D mutation causes decreased AHI1 stability because
      there is a 50% reduction in AHI1-V443D protein levels compared with wild type
      AHI1. Huntingtin-associated protein-1 (Hap1) is a regulatory protein that binds
      Ahi1, and Hap1 knock-out mice have been reported to have JBTS-like phenotypes,
      suggesting a role for Hap1 in ciliogenesis. Fibroblasts and neurons with Hap1
      deficiency form PC with normal growth factor-induced ciliary signaling,
      indicating that the Hap1 JBTS phenotype is likely not through effects at PC.
      These results also suggest that the binding of Ahi1 and Hap1 may not be critical
      for ciliary function. However, we show that HAP1 has decreased binding to AHI1
      V443D indicating that this altered binding could be responsible for the JBTS-like
      phenotype through an unknown pathway. Thus, these JBTS-associated missense
      mutations alter their subcellular distribution and protein interactions,
      compromising functions of AHI1 in cell polarity and cilium-mediated signaling,
      thereby contributing to JBTS.

PMID- 23532846
TI  - Microsomal triglyceride transfer protein inhibition induces endoplasmic reticulum
      stress and increases gene transcription via Ire1alpha/cJun to enhance plasma
      ALT/AST.
AB  - Microsomal triglyceride transfer protein (MTP) is a target to reduce plasma
      lipids because of its indispensable role in triglyceride-rich lipoprotein
      biosynthesis. MTP inhibition in Western diet fed mice decreased plasma
      triglycerides/cholesterol, whereas increasing plasma alanine/aspartate
      aminotransferases (ALT/AST) and hepatic triglycerides/free cholesterol. Free
      cholesterol accumulated in the endoplasmic reticulum (ER) and mitochondria
      resulting in ER and oxidative stresses. Mechanistic studies revealed that MTP
      inhibition increased transcription of the GPT/GOT1 genes through up-regulation of
      the IRE1alpha/cJun pathway leading to increased synthesis and release of
      ALT1/AST1. Thus, transcriptional up-regulation of GPT/GOT1 genes is a major
      mechanism, in response to ER stress, elevating plasma transaminases. Increases in
      plasma and tissue transaminases might represent a normal response to stress for
      survival.

PMID- 23532847
TI  - Group A streptococcal cysteine protease cleaves epithelial junctions and
      contributes to bacterial translocation.
AB  - BACKGROUND: Group A Streptococcus (GAS) translocates across the host epithelial
      barrier. RESULTS: Streptococcal pyrogenic exotoxin B (SpeB) directly cleaves
      junctional proteins. CONCLUSION: The proteolytic efficacy of SpeB allows GAS to
      translocate across the epithelial barrier. SIGNIFICANCE: SpeB-mediated
      dysfunction of the epithelial barrier may have important implications for not
      only bacterial invasion but also dissemination of other virulence factors
      throughout intercellular spaces. Group A Streptococcus (GAS) is an important
      human pathogen that possesses an ability to translocate across the epithelial
      barrier. In this study, culture supernatants of tested GAS strains showed
      proteolytic activity against human occludin and E-cadherin. Utilizing various
      types of protease inhibitors and amino acid sequence analysis, we identified SpeB
      (streptococcal pyrogenic exotoxin B) as the proteolytic factor that cleaves E
      cadherin in the region neighboring the calcium-binding sites within the
      extracellular domain. The cleaving activities of culture supernatants from
      several GAS isolates were correlated with the amount of active SpeB, whereas
      culture supernatants from an speB mutant showed no such activities. Of note, the
      wild type strain efficiently translocated across the epithelial monolayer along
      with cleavage of occludin and E-cadherin, whereas deletion of the speB gene
      compromised those activities. Moreover, destabilization of the junctional
      proteins was apparently relieved in cells infected with the speB mutant, as
      compared with those infected with the wild type. Taken together, our findings
      indicate that the proteolytic efficacy of SpeB in junctional degradation allows
      GAS to invade deeper into tissues.

PMID- 23532848
TI  - Fibroblast growth factor inducible (Fn14)-specific antibodies concomitantly
      display signaling pathway-specific agonistic and antagonistic activity.
AB  - BACKGROUND: Fn14 is a therapeutic target in various diseases. RESULTS: Anti-Fn14
      antibodies activate the alternative NFkappaB pathway but not other Fn14-related
      activities induced by soluble or membrane-bound TWEAK. FcgammaR-bound anti-Fn14
      antibodies, however, activate the full spectrum of Fn14-associated activities.
      CONCLUSION: Anti-Fn14 antibodies elicit agonistic activities differing from those
      of the natural Fn14 ligand TWEAK. SIGNIFICANCE: These findings influence the
      rationale of designing Fn14-targeted therapies. The Fn14-specific monoclonal
      antibodies PDL192 and P4A8, which are under consideration in clinical trials,
      showed no agonistic activity with respect to IL8 production and cell death
      induction. However, oligomerization with protein G or binding to Fcgamma
      receptors converted both anti-Fn14 antibodies into potent agonists. TNF-like weak
      inducer of apoptosis (TWEAK), the ligand of Fn14, occurs naturally in two forms
      with partly different signaling capabilities, as a membrane-bound ligand and as a
      soluble trimeric molecule. Although membrane TWEAK strongly triggers all Fn14
      associated pathways, soluble TWEAK predominately triggers the alternative nuclear
      factor kappaB (NFkappaB) pathway and enhances TNF-induced cell death but has only
      a poor effect on the classical NFkappaB pathway and chemokine production. Thus,
      the oligomerized and FcgammaR-bound anti-Fn14 mAbs mimicked the activity of
      membrane TWEAK. Notably, both anti-Fn14 antibodies significantly triggered p100
      processing, the hallmark of the alternative NFkappaB pathway, and therefore
      resembled soluble TWEAK. In contrast to the latter, however, the anti-Fn14s
      showed no effect on TNF receptor 1-induced cell death and P4A8 even blocked the
      corresponding TWEAK response. Thus, we showed that Fn14 antibodies display an
      alternative NFkappaB pathway-specific agonistic activity but fail to phenocopy
      other activities of soluble TWEAK, whereas oligomerized or FcgammaR-bound Fn14
      antibodies fully mimic the activity of membrane TWEAK. In view of the trivalent
      nature of the TWEAK-Fn14 interaction, this suggests that the alternative NFkappaB
      pathway is uniquely responsive already to Fn14 dimerization enabling antibodies
      to elicit an unnatural response pattern distinct from that of the naturally
      occurring Fn14 ligands.

PMID- 23532849
TI  - A novel automethylation reaction in the Aspergillus nidulans LaeA protein
      generates S-methylmethionine.
AB  - The filamentous fungi in the genus Aspergillus are opportunistic plant and animal
      pathogens that can adapt to their environment by producing various secondary
      metabolites, including lovastatin, penicillin, and aflatoxin. The synthesis of
      these small molecules is dependent on gene clusters that are globally regulated
      by the LaeA protein. Null mutants of LaeA in all pathogenic fungi examined to
      date show decreased virulence coupled with reduced secondary metabolism. Although
      the amino acid sequence of LaeA contains the motifs characteristic of seven-beta
      strand methyltransferases, a methyl-accepting substrate of LaeA has not been
      identified. In this work we did not find a methyl-accepting substrate in
      Aspergillus nidulans with various assays, including in vivo S-adenosyl-[methyl
      (3)H]methionine labeling, targeted in vitro methylation experiments using
      putative protein substrates, or in vitro methylation assays using whole cell
      extracts grown under different conditions. However, in each experiment LaeA was
      shown to self-methylate. Amino acid hydrolysis of radioactively labeled LaeA
      followed by cation exchange and reverse phase chromatography identified
      methionine as the modified residue. Point mutations show that the major site of
      modification of LaeA is on methionine 207. However, in vivo complementation
      showed that methionine 207 is not required for the biological function of LaeA.
      LaeA is the first protein to exhibit automethylation at a methionine residue.
      These findings not only indicate LaeA may perform novel chemistry with S
      adenosylmethionine but also provide new insights into the physiological function
      of LaeA.

PMID- 23532850
TI  - Discs large 1 (Dlg1) scaffolding protein participates with clathrin and adaptator
      protein complex 1 (AP-1) in forming Weibel-Palade bodies of endothelial cells.
AB  - Weibel-Palade bodies (WPBs) are specific cigar-shaped granules that store von
      Willebrand factor (VWF) for its regulated secretion by endothelial cells. The
      first steps of the formation of these granules at the trans-Golgi network
      specifically require VWF aggregation and an external scaffolding complex that
      contains the adaptator protein complex 1 (AP-1) and clathrin. Discs large 1
      (Dlg1) is generally considered to be a modular scaffolding protein implicated in
      the control of cell polarity in a large variety of cells by specific recruiting
      of receptors, channels, or signaling proteins to specialized zones of the plasma
      membrane. We propose here that in endothelial cells, Dlg1, in a complex with AP-1
      and clathrin, participates in the biogenesis of WPBs. Supporting data show that
      Dlg1 colocalizes with microtubules, intermediate filaments, and Golgi markers.
      Tandem mass spectrometry experiments led to the identification of clathrin as an
      Dlg1-interacting partner. Interaction was confirmed by in situ proximity ligation
      assays. Furthermore, AP-1 and VWF immunoprecipitate and colocalize with Dlg1 in
      the juxtanuclear zone. Finally, Dlg1 depletion by siRNA duplexes disrupts trans
      Golgi network morphology and WPB formation. Our results provide the first
      evidence for an unexpected role of Dlg1 in controlling the formation of specific
      secretory granules involved in VWF exocytosis in endothelial cells.

PMID- 23532851
TI  - FoxO1 negatively regulates cellular antiviral response by promoting degradation
      of IRF3.
AB  - Viral infection causes activation of the transcription factor IRF3, which is
      critical for production of type I interferons (IFNs) and innate antiviral immune
      response. How virus-induced type I IFN signaling is controlled is not fully
      understood. Here we identified the transcription factor FoxO1 as a negative
      regulator for virus-triggered IFN-beta induction. Overexpression of FoxO1
      inhibited virus-triggered ISRE activation, IFN-beta induction as well as cellular
      antiviral response, whereas knockdown of FoxO1 had opposite effects. FoxO1
      interacted with IRF3 in a viral infection-dependent manner and promoted K48
      linked polyubiquitination and degradation of IRF3 in the cytosol. Furthermore,
      FoxO1-mediated degradation of IRF3 was independent of the known E3 ubiquitin
      ligases for IRF3, including RBCK1 and RAUL. Our findings thus suggest that FoxO1
      negatively regulates cellular antiviral response by promoting IRF3 ubiquitination
      and degradation, providing a previously unknown mechanism for control of type I
      IFN induction and cellular antiviral response.

PMID- 23532852
TI  - A separate pool of cardiac phospholemman that does not regulate or associate with
      the sodium pump: multimers of phospholemman in ventricular muscle.
AB  - BACKGROUND: Phospholemman regulates the plasmalemmal sodium pump in excitable
      tissues. RESULTS: In cardiac muscle, a subpopulation of phospholemman with a
      unique phosphorylation signature associates with other phospholemman molecules
      but not with the pump. CONCLUSION: Phospholemman oligomers exist in cardiac
      muscle. SIGNIFICANCE: Much like phospholamban regulation of SERCA, phospholemman
      exists as both a sodium pump inhibiting monomer and an unassociated oligomer.
      Phospholemman (PLM), the principal quantitative sarcolemmal substrate for protein
      kinases A and C in the heart, regulates the cardiac sodium pump. Much like
      phospholamban, which regulates the related ATPase SERCA, PLM is reported to
      oligomerize. We investigated subpopulations of PLM in adult rat ventricular
      myocytes based on phosphorylation status. Co-immunoprecipitation identified two
      pools of PLM: one not associated with the sodium pump phosphorylated at Ser(63)
      and one associated with the pump, both phosphorylated at Ser(68) and
      unphosphorylated. Phosphorylation of PLM at Ser(63) following activation of PKC
      did not abrogate association of PLM with the pump, so its failure to associate
      with the pump was not due to phosphorylation at this site. All pools of PLM co
      localized to cell surface caveolin-enriched microdomains with sodium pump alpha
      subunits, despite the lack of caveolin-binding motif in PLM. Mass spectrometry
      analysis of phosphospecific immunoprecipitation reactions revealed no unique
      protein interactions for Ser(63)-phosphorylated PLM, and cross-linking reagents
      also failed to identify any partner proteins for this pool. In lysates from
      hearts of heterozygous transgenic animals expressing wild type and
      unphosphorylatable PLM, Ser(63)-phosphorylated PLM co-immunoprecipitated
      unphosphorylatable PLM, confirming the existence of PLM multimers.
      Dephosphorylation of the PLM multimer does not change sodium pump activity. Hence
      like phospholamban, PLM exists as a pump-inhibiting monomer and an unassociated
      oligomer. The distribution of different PLM phosphorylation states to different
      pools may be explained by their differential proximity to protein phosphatases
      rather than a direct effect of phosphorylation on PLM association with the pump.

PMID- 23532853
TI  - Identification of a mutant alpha1 Na/K-ATPase that pumps but is defective in
      signal transduction.
AB  - BACKGROUND: It has not been possible to study the pumping and signaling functions
      of Na/K-ATPase independently in live cells. RESULTS: Both cell-free and cell
      based assays indicate that the A420P mutation abolishes the Src regulatory
      function of Na/K-ATPase. CONCLUSION: A420P mutant has normal pumping but not
      signaling function. SIGNIFICANCE: Identification of Src regulation-null mutants
      is crucial for addressing physiological role of Na/K-ATPase. The alpha1 Na/K
      ATPase possesses both pumping and signaling functions. However, it has not been
      possible to study these functions independently in live cells. We have identified
      a 20-amino acid peptide (Ser-415 to Gln-434) (NaKtide) from the nucleotide
      binding domain of alpha1 Na/K-ATPase that binds and inhibits Src in vitro. The N
      terminus of NaKtide adapts a helical structure. In vitro kinase assays showed
      that replacement of residues that contain a bulky side chain in the helical
      structure of NaKtide by alanine abolished the inhibitory effect of the peptide on
      Src. Similarly, disruption of helical structure by proline replacement, either
      single or in combination, reduced the inhibitory potency of NaKtide on Src. To
      identify mutant alpha1 that retains normal pumping function but is defective in
      Src regulation, we transfected Na/K-ATPase alpha1 knockdown PY-17 cells with
      expression vectors of wild type or mutant alpha1 carrying Ala to Pro mutations in
      the region of NaKtide helical structure and generated several stable cell lines.
      We found that expression of either A416P or A420P or A425P mutant fully restored
      the alpha1 content and consequently the pumping capacity of cells. However, in
      contrast to A416P, either A420P or A425P mutant was incapable of interacting and
      regulating cellular Src. Consequently, expression of these two mutants caused
      significant inhibition of ouabain-activated signal transduction and cell growth.
      Thus we have identified alpha1 mutant that has normal pumping function but is
      defective in signal transduction.

PMID- 23532854
TI  - Structural and functional aspects of hetero-oligomers formed by the small heat
      shock proteins alphaB-crystallin and HSP27.
AB  - BACKGROUND: alphaB-crystallin and HSP27 are mammalian intracellular small heat
      shock proteins. RESULTS: These proteins exchange subunits in a rapid and
      temperature-dependent manner. CONCLUSION: This facile subunit exchange suggests
      that differential expression could be used by the cell to regulate the response
      to stress. SIGNIFICANCE: A robust technique defines parameters for the dynamic
      interaction between the major mammalian small heat shock proteins. Small heat
      shock proteins (sHSPs) exist as large polydisperse species in which there is
      constant dynamic subunit exchange between oligomeric and dissociated forms. Their
      primary role in vivo is to bind destabilized proteins and prevent their
      misfolding and aggregation. alphaB-Crystallin (alphaB) and HSP27 are the two most
      widely distributed and most studied sHSPs in the human body. They are coexpressed
      in different tissues, where they are known to associate with each other to form
      hetero-oligomeric complexes. In this study, we aimed to determine how these two
      sHSPs interact to form hetero-oligomers in vitro and whether, by doing so, there
      is an increase in their chaperone activity and stability compared with their homo
      oligomeric forms. Our results demonstrate that HSP27 and alphaB formed
      polydisperse hetero-oligomers in vitro, which had an average molecular mass that
      was intermediate of each of the homo-oligomers and which were more thermostable
      than alphaB, but less so than HSP27. The hetero-oligomer chaperone function was
      found to be equivalent to that of alphaB, with each being significantly better in
      preventing the amorphous aggregation of alpha-lactalbumin and the amyloid fibril
      formation of alpha-synuclein in comparison with HSP27. Using mass spectrometry to
      monitor subunit exchange over time, we found that HSP27 and alphaB exchanged
      subunits 23% faster than the reported rate for HSP27 and alphaA and almost twice
      that for alphaA and alphaB. This represents the first quantitative evaluation of
      alphaB/HSP27 subunit exchange, and the results are discussed in the broader
      context of regulation of function and cellular proteostasis.

PMID- 23532855
TI  - Major histocompatibility complex (MHC) class II-peptide complexes arrive at the
      plasma membrane in cholesterol-rich microclusters.
AB  - BACKGROUND: Antigen-specific CD4 T cells are activated by small numbers of
      antigenic peptide-MHC class II (pMHC-II) complexes on dendritic cells (DCs).
      RESULTS: Newly generated pMHC-II complexes are present in small clusters on the
      DC surface. CONCLUSION: pMHC-II clusters permit efficient T cell activation.
      SIGNIFICANCE: The appearance of clustered pMHC-II reveals the organization of the
      T cell antigen receptor ligand on the DC surface. Dendritic cells (DCs) function
      by stimulating naive antigen-specific CD4 T cells to proliferate and secrete a
      variety of immunomodulatory factors. The ability to activate naive T cells comes
      from the capacity of DCs to internalize, degrade, and express peptide fragments
      of antigenic proteins on their surface bound to MHC class II molecules (MHC-II).
      Although DCs express tens of thousands of distinct MHC-II, very small amounts of
      specific peptide-MHC-II complexes are required to interact with and activate T
      cells. We now show that stimulatory MHC-II I-A(k)-HEL(46-61) complexes that move
      from intracellular antigen-processing compartments to the plasma membrane are not
      randomly distributed on the DC surface. Confocal immunofluorescence microscopy
      and quantitative immunoelectron microscopy reveal that the majority of newly
      generated MHC-II I-A(k)-HEL(46-61) complexes are expressed in sub-100-nm
      microclusters on the DC membrane. These microclusters are stabilized in
      cholesterol-containing microdomains, and cholesterol depletion inhibits the
      stability of these clusters as well as the ability of the DCs to function as
      antigen-presenting cells. These results demonstrate that specific cohorts of
      peptide-MHC-II complexes expressed on the DC surface are present in cholesterol
      dependent microclusters and that cluster integrity is important for antigen
      specific naive CD4 T cell activation by DCs.

PMID- 23532856
TI  - beta2 integrin-mediated cell-cell contact transfers active myeloperoxidase from
      neutrophils to endothelial cells.
AB  - Atherosclerosis and vasculitis both feature inflammation mediated by neutrophil
      endothelial cell (EC) contact. Neutrophil myeloperoxidase (MPO) can disrupt
      normal EC function, although the mechanism(s) by which MPO is transferred to ECs
      are unknown. We tested the hypothesis that close, beta2 integrin-dependent
      neutrophil-EC contact mediates MPO transfer from neutrophils to ECs. We used
      sensitive MPO assays and flow cytometry to detect MPO in ECs and demonstrate that
      ECs acquired MPO when contacted by neutrophils directly but not when ECs and
      neutrophils were separated in Transwells. The transfer was dependent on
      neutrophil number, exposure time, and incubation temperature. Transfer occurred
      in several EC types, increased with endotoxin, was not accompanied by MPO release
      into the medium, and was not abrogated by inhibiting degranulation to
      secretagogues. Confocal microscopy showed MPO internalization by ECs with
      cytoplasmic and nuclear staining. Neutrophils and ECs formed intimate contact
      sites demonstrated by electron microscopy. Blocking CD11b or CD18 beta2 integrin
      chains, or using neutrophils from CD11b gene-deleted mice, reduced MPO transfer.
      EC-acquired MPO was enzymatically active, as demonstrated by its ability to
      oxidize the fluorescent probe aminophenyl fluorescein in the presence of a
      hydrogen peroxide source. The data suggest an alternative to EC uptake of soluble
      MPO, namely the cell contact-dependent, beta2 integrin-mediated transfer from
      neutrophils. The findings could be of therapeutic relevance in atherosclerosis
      and vasculitis.

PMID- 23532857
TI  - Smoothened oligomerization/higher order clustering in lipid rafts is essential
      for high Hedgehog activity transduction.
AB  - The Hedgehog (Hh) signaling pathway plays evolutionarily conserved roles in
      controlling embryonic development and tissue homeostasis, and its dysregulation
      has been implicated in many human diseases including congenital disorder and
      cancer. The Hh pathway has a unique signal reception system that includes two
      membrane proteins, the receptor Patched (Ptc) and the transducer Smoothened
      (Smo). In the Hh signaling cascade, Smo plays a critical role in controlling
      transduction of Hh gradient signal from the outside into the inside of cells.
      Although the Smo downstream signal transduction has been intensively studied, the
      mechanism by which Smo on the plasma membrane is regulated has not been fully
      understood. As a specific membrane structure of metazoan cells, lipid rafts act
      as a platform to regulate signal transduction by forming a nanoscale cluster
      through protein-protein or protein-lipid interactions. However, it remains
      largely unknown whether lipid rafts are also involved in the regulation of Hh
      signal transduction. Here, we show that Smo extracellular domain (N terminus) and
      transmembrane domains form oligomers/higher order clusters in response to Hh
      signal. Furthermore, we identify that lipid rafts on the plasma membrane are
      essential for high level activity of Smo during the Hh signal transduction.
      Finally, our observation suggests that oligomerization/higher order clustering of
      Smo C-terminal cytoplasmic tail (C-tail) is essential for the transduction of
      high level Hh signal. Collectively, our data support that in response to Hh
      gradient signals, Smo transduces high level Hh signal by forming oligomers/higher
      order clusters in the lipid rafts of cell plasma membrane.

PMID- 23532858
TI  - Voltinism of Diabrotica speciosa (Coleoptera: Chrysomelidae) in Argentina:
      latitudinal clines and implications for damage anticipation.
AB  - BACKGROUND: Diabrotica speciosa (Germar) is an important pest in South America.
      Both the adults and the larvae are polyphagous, and its most susceptible host is
      maize. Factors behind the appearance of adults in the field and geographical
      variations in voltinism are unknown. This hinders the chances of implementing
      rational control strategies. RESULTS: This study compiles field collection data
      from four agricultural regions of Argentina to examine the number of generations
      and phenology of D. speciosa in the field. These data are correlated with
      climatic data in order to provide evidence of regional variations and probable
      environmental causes for the appearance of adult generations in the field.
      Results indicate that temperature has an important role in the appearance of new
      generations in the temperate distribution areas of D. speciosa, but not within
      its subtropical range, where teneral adults appeared all year round. CONCLUSION:
      Results suggest that the emergence of adults may be elicited by weekly average
      temperatures above 13  degrees C. In the temperate distribution areas of D.
      speciosa there could be at least three generations a year, and in the subtropical
      region at least five. No obvious or discrete voltinism pattern could be observed
      for D. speciosa in southern South America.

PMID- 23532860
TI  - Galantamine potentiates the neuroprotective effect of memantine against NMDA
      induced excitotoxicity.
AB  - The combination of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist,
      with an acetylcholinesterase inhibitor (AChEI) is the current standard of care in
      Alzheimer's disease (AD). Galantamine, an AChEI currently marketed for the
      treatment of AD, exerts memory-enhancing and neuroprotective effects via
      activation of nicotinic acetylcholine receptors (nAChRs). Here, we investigated
      the neuroprotective properties of galantamine in primary cultures of rat cortical
      neurons when given alone or in combination with memantine. In agreement with
      previous findings, we found that memantine was fully effective in reversing NMDA
      toxicity at concentrations of 2.5 and 5 MUmol/L. Galantamine also completely
      reversed NMDA toxicity at a concentration of 5 MUmol/L. The alpha7 and
      alpha4beta2 nAChR antagonists, methyllycaconitine, and dihydro-beta-erythroidine
      blocked the neuroprotective effect of galantamine, demonstrating the involvement
      of nAChRs. The combination of memantine with galantamine produced synergistic
      actions, such that full neuroprotective efficacy, was obtained at inactive
      concentrations of memantine (0.1 MUmol/L) and galantamine (1 MUmol/L). A similar
      potentiation was also observed when memantine was replaced with ifenprodil,
      suggesting a possible involvement of the NR2B subunit of the NMDA receptor. In
      summary, our study reports for the first time at a cellular level that memantine
      and galantamine interact on the same excitotoxic cascade and that the combination
      of these two drugs can result in a remarkable neuroprotective effect.

PMID- 23532859
TI  - Cis-regulatory sequence variation and association with Mycoplasma load in natural
      populations of the house finch (Carpodacus mexicanus).
AB  - Characterization of the genetic basis of fitness traits in natural populations is
      important for understanding how organisms adapt to the changing environment and
      to novel events, such as epizootics. However, candidate fitness-influencing loci,
      such as regulatory regions, are usually unavailable in nonmodel species. Here, we
      analyze sequence data from targeted resequencing of the cis-regulatory regions of
      three candidate genes for disease resistance (CD74, HSP90alpha, and LCP1) in
      populations of the house finch (Carpodacus mexicanus) historically exposed
      (Alabama) and naive (Arizona) to Mycoplasma gallisepticum. Our study, the first
      to quantify variation in regulatory regions in wild birds, reveals that the
      upstream regions of CD74 and HSP90alpha are GC-rich, with the former exhibiting
      unusually low sequence variation for this species. We identified two SNPs,
      located in a GC-rich region immediately upstream of an inferred promoter site in
      the gene HSP90alpha, that were significantly associated with Mycoplasma pathogen
      load in the two populations. The SNPs are closely linked and situated in
      potential regulatory sequences: one in a binding site for the transcription
      factor nuclear NFYalpha and the other in a dinucleotide microsatellite ((GC)6).
      The genotype associated with pathogen load in the putative NFYalpha binding site
      was significantly overrepresented in the Alabama birds. However, we did not see
      strong effects of selection at this SNP, perhaps because selection has acted on
      standing genetic variation over an extremely short time in a highly recombining
      region. Our study is a useful starting point to explore functional relationships
      between sequence polymorphisms, gene expression, and phenotypic traits, such as
      pathogen resistance that affect fitness in the wild.

PMID- 23532861
TI  - ABL1 in thalamus is associated with safety but not fear learning.
AB  - In auditory fear conditioning a tone is paired with a footshock, establishing
      long lasting fear memory to the tone. In safety learning these stimuli are
      presented in an unpaired non-overlapping manner and enduring memories to the tone
      as a safety signal are formed. Although these paradigms utilize the same sensory
      stimuli different memories are formed leading to distinct behavioral outcome. In
      this study we aimed to explore whether fear conditioning and safety learning lead
      to different molecular changes in thalamic area that receives tone and shock
      inputs. Toward that end, we used antibody microarrays to detect changes in
      proteins levels in this brain region. The levels of ABL1, Bog, IL1B, and Tau
      proteins in thalamus were found to be lower in the group trained for safety
      learning compared to the fear conditioning group 6 h after training. The levels
      of these proteins were not different between safety learning and fear
      conditioning trained groups in auditory cortex. Western blot analysis revealed
      that the ABL1 protein level in thalamus is reduced specifically by safety
      learning but not fear conditioning when compared to naive rats. These results
      show that safety learning leads to activation of auditory thalamus differently
      from fear conditioning and to a decrease in the level of ABL1 protein in this
      brain region. Reduction in ABL1 level in thalamus may affect neuronal processes,
      such as morphogenesis and synaptic efficacy shown to be intimately regulated by
      changes in this kinase level.

PMID- 23532862
TI  - Effect of total knee arthroplasty on type II diabetes mellitus and hypertension:
      A prospective study.
AB  - CONTEXT: Advanced osteoarthritis of knee joint if bilateral, severely restricts
      patient mobility. This acts as an aggravating factor for pre existing comorbid
      elements of metabolical syndrome (MS) like Type II diabetes mellitus and
      hypertension as patients are unable to carry out therapeutic walks. Successfully
      implanted total knee arthroplasty (TKA) increases physical activity and enables
      to carry out therapeutic walks thus may help in better control of type II
      diabetes mellitus and hypertension. The objective of this prospective study was
      to find whether TKA for osteoarthritis knee had any effect to improve blood
      glucose levels and reduce blood pressure. MATERIALS AND METHODS: A prospective
      study was done in which patients operated for tricompartmental osteoarthritis of
      knee with associated comorbidities like Type II diabetes mellitus or hypertension
      during a period of 2008 and 2009 were studied. One hundred and twenty patients
      were enrolled (55 diabetics, 65 hypertensives) who met our inclusion criteria.
      Preoperative knee society score, lower extremity activity scale fasting blood
      glucose level and systolic and diastolic blood pressure were compared with one
      year followup values. The KSS and LEAS scores were analysed by the Wilcoxon
      signed ranked test, while the fasting blood glucose (FBG) levels and systolic and
      diastolic blood pressure levels were analysed by paired 't' test. RESULTS: The
      reduction of systolic blood pressure by 8 mmHg (t = 5.6, P value < 0.05) and
      diastolic blood pressure by 6 mmHg (t = 7.6, P value < 0.05) was recorded which
      was statistically significant. However, no statistically significant effect on
      fasting blood glucose levels was observed (t = -0.77, P value = 0.442). KSS
      improved in DM from preoperative 29 to 86 and LEAS improved from 6.7 to 11.3.
      CONCLUSIONS: Authors are of the opinion that successful total knee replacement
      results in increased physical activity and reduces blood pressure (systolic and
      diastolic) in hypertensives. However, the same is not seen in blood glucose
      level. Increased physical activity and reduced dependence on NSAIDS
      postoperatively, may be contributing in reduction of systolic and diastolic blood
      pressure. Further studies in this aspect are necessary.

PMID- 23532863
TI  - Combination therapy with melatonin and dexamethasone in a mouse model of
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major cause of preventable death and morbidity
      in young adults. This complex condition is characterized by a significant blood
      brain barrier leakage that stems from cerebral ischemia, inflammation, and redox
      imbalances in the traumatic penumbra of the injured brain. Recovery of function
      after TBI is partly through neuronal plasticity. In order to test whether
      combination therapy with melatonin and dexamethasone (DEX) might improve
      functional recovery, a controlled cortical impact (CCI) was performed in adult
      mice, acting as a model of TBI. Once trauma has occurred, combating these
      exacerbations is the keystone of an effective TBI therapy. The therapy with
      melatonin (10  mg/kg) and DEX (0.025  mg/kg) is able to reduce edema and brain
      infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride
      staining across the brain sections. Melatonin- and DEX-mediated improvements in
      tissue histology shown by the reduction in lesion size and an improvement in
      apoptosis level further support the efficacy of combination therapy. The
      combination therapy also blocked the infiltration of astrocytes and reduced CCI
      mediated oxidative stress. In addition, we have also clearly demonstrated that
      the combination therapy significantly ameliorated neurological scores. Taken
      together, our results clearly indicate that combination therapy with melatonin
      and DEX presents beneficial synergistic effects, and we consider it an avenue for
      further development of novel combination therapeutic agents in the treatment of
      TBI that are more effective than a single effector molecule.

PMID- 23532864
TI  - High-throughput screening for terpene-synthase-cyclization activity and directed
      evolution of a terpene synthase.

PMID- 23532865
TI  - Outpatient parenteral antimicrobial therapy.

PMID- 23532866
TI  - Ultrasound imaging for lumbar punctures and epidural catheterisations: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To determine whether ultrasound imaging can reduce the risk of failed
      lumbar punctures or epidural catheterisations, when compared with standard
      palpation methods, and whether ultrasound imaging can reduce traumatic
      procedures, insertion attempts, and needle redirections. DESIGN: Systematic
      review and meta-analysis of randomised controlled trials. DATA SOURCES: Ovid
      Medline, Embase, and Cochrane Central Register of Controlled Trials up to May
      2012, without restriction by language or publication status. REVIEW METHODS:
      Randomised trials that compared ultrasound imaging with standard methods (no
      imaging) in the performance of a lumbar puncture or epidural catheterisation were
      identified. RESULTS: 14 studies with a total of 1334 patients were included (674
      patients assigned to the ultrasound group, 660 to the control group). Five
      studies evaluated lumbar punctures and nine evaluated epidural catheterisations.
      Six of 624 procedures conducted in the ultrasound group failed; 44 of 610
      procedures in the control group failed. Ultrasound imaging reduced the risk of
      failed procedures (risk ratio 0.21 (95% confidence interval 0.10 to 0.43),
      P<0.001). Risk reduction was similar when subgroup analysis was performed for
      lumbar punctures (risk ratio 0.19 (0.07 to 0.56), P=0.002) or epidural
      catheterisations (0.23 (0.09 to 0.60), P=0.003). Ultrasound imaging also
      significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to
      0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64
      to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00
      (-1.24 to -0.75), P<0.001). CONCLUSIONS: Ultrasound imaging can reduce the risk
      of failed or traumatic lumbar punctures and epidural catheterisations, as well as
      the number of needle insertions and redirections. Ultrasound may be a useful
      adjunct for these procedures.

PMID- 23532867
TI  - Taking the sting out of lumbar puncture.

PMID- 23532868
TI  - Would doctors routinely asking older patients about their memory improve dementia
      outcomes? No.

PMID- 23532869
TI  - Painful blisters on the hand.

PMID- 23532870
TI  - Would doctors routinely asking older patients about their memory improve dementia
      outcomes? Yes.

PMID- 23532871
TI  - Longer term survival of a child with autosomal recessive cutis laxa due to a
      mutation in FBLN4.
AB  - Autosomal recessive cutis laxa (ARCL) is a clinically and genetically
      heterogeneous group of disorders characterized by loose, inelastic skin and
      variable systemic involvement and severity. Mutations in the FBLN4 gene are
      associated with ARCL1B. Fibulin-4 is important in elastic fiber formation and
      smooth muscle cell differentiation. We describe herein an 8-year-old boy who
      presented with severe aortic root dilatation and arterial tortuosity at 1 year of
      age which required surgical repair. His parents were consanguineous and there was
      a family history of three brothers who died early in life with an unknown type of
      connective tissue disorder in the 1960s. Both parents of the patient reported
      here were related to these three boys. We used a homozygosity mapping strategy
      with a 900K SNP array and identified FBLN4 as a candidate gene in an extended
      region of homozygosity. We sequenced this gene in the patient and identified a
      homozygous non-synonymous mutation at c.376G>A (p.Glu126Lys) in exon 5 that was
      predicted to be damaging. ARCL1B has most typically been associated with early
      demise but our report suggests that long-term survival is possible. With this
      longer term survival we are learning more about the natural history of this
      disorder, which includes baroreceptor reflex failure and low bone mineral density
      in this patient.

PMID- 23532872
TI  - Construction and in vitro/in vivo targeting of PSMA-targeted nanoscale
      microbubbles in prostate cancer.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA) is a highly specific
      biological marker and treatment target for prostate cancer. So ultrasound
      molecular imaging using PSMA antibody-loaded targeted nanoscale microbubbles
      (MBs) may contribute to the early diagnosis of prostate cancer. METHODS: PSMA
      monoclonal antibody-loaded targeted nanoscale MBs were prepared using biotin
      avidin technology. Antibody binding was evaluated with immunofluorescence. Using
      MKN45 gastric cancer cells as controls, the targeting capability of the targeted
      MBs was observed in prostate cancer cells (LNCaP and C4-2) under optical
      microscope. Contrast enhancement was monitored by an ultrasound system in C4-2,
      LNCaP, and MKN45 transplanted tumors in nude mice. The arrival time, time to
      peak, peak intensity, and duration of contrast enhancement of targeted and blank
      nanoscale MBs were compared and analyzed. RESULTS: Targeted PSMA monoclonal
      antibody-loaded nanoscale MBs were successfully synthesized. These MBs were
      stable and could specifically bind to LNCaP and C4-2 cells in vitro but did not
      bind to MKN45 cells. There were significant differences in peak intensity and
      duration of contrast enhancement between targeted and blank nanoscale MBs in both
      transplanted prostate tumors (P < 0.05). Among the three types of transplanted
      tumors with targeted nanoscale MBs, the peak intensity was significantly higher
      in prostate tumors (LNCaP and C4-2) than in gastric tumors (MKN45) (P < 0.05).
      CONCLUSIONS: PSMA monoclonal antibody-loaded targeted nanoscale MBs can target
      and bind to prostate cancer cells specifically and allow for obvious contrast
      enhancement in vivo. Therefore, this study lays a foundation for early diagnosis
      and targeted therapy for prostate cancer.

PMID- 23532873
TI  - Investigations on diffusion limitations of biocatalyzed reactions in amphiphilic
      polymer conetworks in organic solvents.
AB  - The use of enzymes as biocatalysts in organic media is an important issue in
      modern white biotechnology. However, their low activity and stability in those
      media often limits their full-scale application. Amphiphilic polymer conetworks
      (APCNs) have been shown to greatly activate entrapped enzymes in organic
      solvents. Since these nanostructured materials are not porous, the bioactivity of
      the conetworks is strongly limited by diffusion of substrate and product. The
      present manuscript describes two different APCNs as nanostructured
      microparticles, which showed greatly increased activities of entrapped enzymes
      compared to those of the already activating membranes and larger particles. We
      demonstrated this on the example of APCN particles based on PHEA-l-PDMS loaded
      with alpha-Chymotrypsin, which resulted in an up to 28,000-fold higher activity
      of the enzyme compared to the enzyme powder. Furthermore, lipase from Rhizomucor
      miehei entrapped in particles based on PHEA-l-PEtOx was tested in n-heptane,
      chloroform, and substrate. Specific activities in smaller particles were 10- to
      100-fold higher in comparison to the native enzyme. The carrier activity of PHEA
      l-PEtOx microparticles was tenfold higher with some 25-50-fold lower enzyme
      content compared to a commercial product.

PMID- 23532874
TI  - Humanin binds MPP8: mapping interaction sites of the peptide and protein.
AB  - Humanin (HN), a 24-amino acid peptide encoded by the mitochondrial 16S rRNA gene,
      was discovered by screening a cDNA library from the occipital cortex of a patient
      with Alzheimer's disease (AD) for a protection factor against AD-relevant
      insults. Earlier, using the yeast two-hybrid system, we have identified the M
      phase phosphoprotein 8 (MPP8) as a binding partner for HN. In the present work,
      we further confirmed interaction of HN with MPP8 in co-immunoprecipitation
      experiments and localized an MPP8-binding site in the region between 5 and 12 aa.
      of HN. We have also shown that an MPP8 fragment (residues 431-560) is sufficient
      to bind HN. Further studies on functional consequences of the interaction between
      the potential oncopetide and the oncoprotein may elucidate some aspects of the
      molecular mechanisms of carcinogenesis.

PMID- 23532876
TI  - Polymorphisms at regions 1p22.1 (rs560426) and 8q24 (rs1530300) are risk markers
      for nonsyndromic cleft lip and/or palate in the Brazilian population.

PMID- 23532877
TI  - Radiation-induced spinal cord glioblastoma with cerebrospinal fluid dissemination
      subsequent to treatment of lymphoblastic lymphoma.
AB  - BACKGROUND: Radiation-induced glioma arising in the spinal cord is extremely
      rare. We report a case of radiation-induced spinal cord glioblastoma with
      cerebrospinal fluid (CSF) dissemination 10 years after radiotherapy for T-cell
      lymphoblastic lymphoma. CASE DESCRIPTION: A 32-year-old male with a history of T
      cell lymphoblastic lymphoma presented with progressive gait disturbance and
      sensory disturbance below the T4 dermatome 10 years after mediastinal
      irradiation. Gadolinium-enhanced magnetic resonance (MR) imaging revealed an
      intramedullary tumor extending from the C6 to the T6 level, corresponding to the
      previous radiation site, and periventricular enhanced lesions. In this case, the
      spinal lesion was not directly diagnosed because the patient refused any kind of
      spinal surgery to avoid worsening of neurological deficits. However, based on a
      biopsy of an intracranial disseminated lesion and repeated immmunocytochemical
      examination of CSF cytology, we diagnosed the spinal tumor as a radiation-induced
      glioblastoma. The patient was treated with radiotherapy plus concomitant and
      adjuvant temozolomide. Then, the spinal tumor was markedly reduced in size, and
      the dissemination disappeared. CONCLUSION: We describe our detailed diagnostic
      process and emphasize the diagnostic importance of immunocytochemical analysis of
      CSF cytology.

PMID- 23532879
TI  - Aspiration pneumonia in dogs: treatment, monitoring, and prognosis.
AB  - Aspiration pneumonia and aspiration pneumonitis are associated with significant
      morbidity in both veterinary and human medicine. A variety of medical conditions
      and medications can predispose patients to aspiration. Ideally, aspiration should
      be prevented, but in dogs that develop aspiration pneumonia, close monitoring and
      supportive care are imperative. This article describes antimicrobial treatment,
      fluid therapy, ancillary medical therapy, oxygen therapy, and prognosis for
      aspiration pneumonia.

PMID- 23532880
TI  - Uterine torsion in mares.
AB  - Uterine torsion typically occurs during mid to late gestation and is estimated to
      cause 5% to 10% of all equine obstetric emergencies. Clinical signs include
      abdominal pain that may be mistaken for gastrointestinal distress, parturition,
      or abortion. Uterine torsion is an emergency for the mare and fetus, and early
      recognition and intervention are essential to optimizing the chance of survival.
      This article reviews the etiology, diagnosis, treatment, and prognosis of uterine
      torsion in mares.

PMID- 23532881
TI  - Equine laparoscopy: hemostasis.

PMID- 23532882
TI  - Aspiration pneumonia in dogs: pathophysiology, prevention, and diagnosis.
AB  - Aspiration pneumonia and aspiration pneumonitis are associated with significant
      morbidity in veterinary and human medicine. A variety of medical conditions and
      medications can predispose patients to aspiration, and every precaution should be
      taken to prevent aspiration from occurring. For dogs that aspirate oral or
      gastric contents and subsequently develop pneumonia, monitoring and supportive
      care are imperative. This article discusses the pathophysiology, prevention, and
      diagnosis of aspiration pneumonia.

PMID- 23532883
TI  - New public health agency backs calls for minimum price on alcohol.

PMID- 23532884
TI  - PRAMEing a picture of differentiation therapy for AML?
AB  - Addition of retinoic acid to chemotherapy improves survival of patients with
      acute myeloid leukemia. This effect is more pronounced in leukemias that express
      high levels of PRAME. PRAME is an inhibitor of retinoic acid signaling, which may
      prove to be an important marker for retinoic acid response.

PMID- 23532885
TI  - Classifying MMR variants: time for revised nomenclature in Lynch syndrome.
AB  - Inactivating germline mutations in DNA mismatch repair (MMR) genes are diagnostic
      for Lynch syndrome. However, the clinical significance of missense variants is
      uncertain. A threshold level of compromised MLH1 expression, correlating with
      greater protein instability and MMR functional defect, has been identified to
      help classify the pathogenicity of missense variants.

PMID- 23532886
TI  - Potent antimyeloma activity of a novel ERK5/CDK inhibitor.
AB  - PURPOSE: To analyze the antimyeloma potential of TG02, an ERK5/CDK inhibitory
      drug. EXPERIMENTAL DESIGN: Utilizing different multiple myeloma cell lines we
      determined the effect of TG02 over viability by MTT assays. The apoptotic effect
      over multiple myeloma patient samples was studied ex vivo by cytometry. The
      mechanism of action of TG02 was analyzed in the cell line MM1S, studying its
      effect on the cell cycle, the induction of apoptosis, and the loss of
      mitochondrial membrane potential by cytometry and Western blot. Two models of
      multiple myeloma xenograft were utilized to study the in vivo action of TG02.
      RESULTS: TG02 potently inhibited proliferation and survival of multiple myeloma
      cell lines, even under protective bone marrow niche conditions, and selectively
      induced apoptosis of primary patient-derived malignant plasma cells. TG02
      displayed significant single-agent activity in two multiple myeloma xenograft
      models, and enhanced the in vivo activity of bortezomib and lenalidomide.
      Signaling analyses revealed that the drug simultaneously blocked the activity of
      CDKs 1, 2, and 9 as well as the MAP kinase ERK5 in MM1S cells, leading to cell
      cycle arrest and rapid commitment to apoptosis. TG02 induced robust activation of
      both the intrinsic and extrinsic pathways of apoptosis, and depletion of XIAP and
      the key multiple myeloma survival protein Mcl-1. CONCLUSIONS: TG02 is a promising
      new antimyeloma agent that is currently in phase I clinical trials in leukemia
      and multiple myeloma patients.

PMID- 23532887
TI  - Tissue redox activity as a hallmark of carcinogenesis: from early to terminal
      stages of cancer.
AB  - PURPOSE: The study aimed to clarify the dynamics of tissue redox activity (TRA)
      in cancer progression and assess the importance of this parameter for therapeutic
      strategies. EXPERIMENTAL DESIGN: The experiments were carried out on brain
      tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was
      visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro
      by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two
      biochemical parameters were analyzed in parallel: tissue total antioxidant
      capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). RESULTS: In
      the early stage of cancer, the brain tissues were characterized by a shorter
      lived MRI signal than that from healthy brains (indicating a higher reducing
      activity for the nitroxide radical), which was accompanied by an enhancement of
      TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both
      hemispheres were characterized by a longer-lived MRI signal than in healthy
      brains (indicating a high-oxidative activity) that was accompanied by a decrease
      in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also
      affected the redox potential of tissues distant from the primary tumor locus
      (liver and lung). Their oxidative status increased in both stages of cancer.
      CONCLUSIONS: The study shows that tissue redox balance is very sensitive to the
      progression of cancer and can be used as a diagnostic marker of carcinogenesis.
      The study also suggests that the noncancerous tissues of a cancer-bearing
      organism are susceptible to oxidative damage and should be considered a
      therapeutic target.

PMID- 23532888
TI  - Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified
      FOLFOX6) as first-line treatment of metastatic colorectal cancer: the RESPECT
      trial.
AB  - PURPOSE: This randomized, double-blind, placebo-controlled, phase IIb study
      evaluated adding sorafenib to first-line modified FOLFOX6 (mFOLFOX6) for
      metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Patients were
      randomized to sorafenib (400 mg b.i.d.) or placebo, combined with mFOLFOX6
      (oxaliplatin 85 mg/m(2); levo-leucovorin 200 mg/m(2); fluorouracil 400 mg/m(2)
      bolus and 2400 mg/m(2) continuous infusion) every 14 days. Primary endpoint was
      progression-free survival (PFS). Target sample was 120 events in 180 patients for
      >85% power (two-sided alpha = 0.20) to detect an HR = 0.65. RESULTS: Of 198
      patients randomized, median PFS for sorafenib plus mFOLFOX6 was 9.1 months versus
      8.7 months for placebo plus mFOLFOX6 (HR = 0.88; 95% CI, 0.64-1.23; P = 0.46).
      There was no difference between treatment arms for overall survival. Subgroup
      analyses of PFS and overall survival showed no difference between treatment arms
      by KRAS or BRAF status (mutant and wild type). The most common grade 3/4 adverse
      events in the sorafenib and placebo arms were neutropenia (48% vs. 22%),
      peripheral neuropathy (16% vs. 21%), and grade 3 hand-foot skin reaction (20% vs.
      0%). Treatment discontinuation because of adverse events was 9% and 6%,
      respectively. Generally, dose intensity (duration and cumulative doses) was lower
      in the sorafenib arm than in the placebo arm. CONCLUSION: This study did not
      detect a PFS benefit with the addition of sorafenib to first-line mFOLFOX6 for
      mCRC. KRAS and BRAF status did not seem to impact treatment outcomes but the
      subgroups were small. These results do not support further development of
      sorafenib in combination with mFOLFOX6 in molecularly unselected patients with
      mCRC.

PMID- 23532889
TI  - PIK3CA mutation is associated with a favorable prognosis among patients with
      curatively resected esophageal squamous cell carcinoma.
AB  - PURPOSE: PIK3CA encodes the catalytic subunit of PI3K, p110alpha. Mutant PIK3CA
      stimulates the AKT pathway and promotes cancer cell proliferation. PIK3CA
      mutations have been associated with poor prognosis in patients with colorectal or
      lung cancer. In contrast, the relationship between PIK3CA mutations and favorable
      prognoses has been shown in breast cancer. However, the influence of PIK3CA
      mutations on the prognosis of patients with esophageal squamous cell carcinoma
      (ESCC) remains unclear. EXPERIMENTAL DESIGN: Using a nonbiased database of 219
      curatively resected ESCCs and eight esophageal cancer cell lines, we evaluated
      PIK3CA mutational status by pyrosequencing. The expression of p53 and
      phosphorylated AKT (i.e., AKT activation) was evaluated by immunohistochemistry.
      RESULTS: PIK3CA mutations in exon 9 and/or 20 were detected in 46 cases (21%). No
      ESCC cell line harbored PIK3CA mutations. PIK3CA mutations were significantly
      associated with phosphorylated AKT expression, but not with p53 expression, sex,
      age at surgery, tobacco use, alcohol use, or histologic grade. Compared with wild
      type PIK3CA cases, patients with PIK3CA mutations in exons 9 and/or 20
      experienced significantly better disease-free survival [log-rank P = 0.0089;
      univariate HR: 0.37, 95% confidence interval (CI): 0.15-0.75, P = 0.0042;
      multivariate HR: 0.34, 95% CI: 0.10-0.86, P = 0.021] and overall survival (log
      rank P = 0.012; univariate HR: 0.38, 95% CI: 0.16-0.78, P = 0.0060; multivariate
      HR: 0.35, 95% CI: 0.10-0.90, P = 0.028). CONCLUSION: PIK3CA mutations in ESCC are
      associated with longer survival, suggesting its role as a prognostic biomarker.
      Future studies are needed to confirm this association and to elucidate the exact
      mechanisms by which PIK3CA mutations affect tumor behavior.

PMID- 23532890
TI  - Tivantinib (ARQ197) displays cytotoxic activity that is independent of its
      ability to bind MET.
AB  - PURPOSE: MET, the high-affinity receptor for hepatocyte growth factor, is
      frequently deregulated in human cancer. Tivantinib (ARQ197; Arqule), a
      staurosporine derivative that binds to the dephosphorylated MET kinase in vitro,
      is being tested clinically as a highly selective MET inhibitor. However, the
      mechanism of action of tivantinib is still unclear. EXPERIMENTAL DESIGN: The
      activity of tivantinib was analyzed in multiple cellular models, including: cells
      displaying c-MET gene amplification, strictly 'addicted' to MET signaling; cells
      with normal c-MET gene copy number, not dependent on MET for growth; cells not
      expressing MET; somatic knockout cells in which the ATP-binding cleft of MET,
      where tivantinib binds, was deleted by homologous recombination; and a cell
      system 'poisoned' by MET kinase hyperactivation, where cells die unless cultured
      in the presence of a specific MET inhibitor. RESULTS: Tivantinib displayed
      cytotoxic activity independently of c-MET gene copy number and regardless of the
      presence or absence of MET. In both wild-type and isogenic knockout cells,
      tivantinib perturbed microtubule dynamics, induced G2/M arrest, and promoted
      apoptosis. Tivantinib did not rescue survival of cells 'poisoned' by MET kinase
      hyperactivation, but further incremented cell death. In all cell models analyzed,
      tivantinib did not inhibit HGF-dependent or -independent MET tyrosine
      autophosphorylation. CONCLUSIONS: We conclude that tivantinib displays cytotoxic
      activity via molecular mechanisms that are independent from its ability to bind
      MET. This notion has a relevant impact on the interpretation of clinical results,
      on the design of future clinical trials, and on the selection of patients
      receiving tivantinib treatment.

PMID- 23532891
TI  - Serial diffusion MRI to monitor and model treatment response of the targeted
      nanotherapy CRLX101.
AB  - PURPOSE: Targeted nanotherapies are being developed to improve tumor drug
      delivery and enhance therapeutic response. Techniques that can predict response
      will facilitate clinical translation and may help define optimal treatment
      strategies. We evaluated the efficacy of diffusion-weighted magnetic resonance
      imaging to monitor early response to CRLX101 (a cyclodextrin-based polymer
      particle containing the DNA topoisomerase I inhibitor camptothecin) nanotherapy
      (formerly IT-101), and explored its potential as a therapeutic response predictor
      using a mechanistic model of tumor cell proliferation. EXPERIMENTAL DESIGN:
      Diffusion MRI was serially conducted following CRLX101 administration in a mouse
      lymphoma model. Apparent diffusion coefficients (ADCs) extracted from the data
      were used as treatment response biomarkers. Animals treated with irinotecan (CPT
      11) and saline were imaged for comparison. ADC data were also input into a
      mathematical model of tumor growth. Histological analysis using cleaved-caspase
      3, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, Ki-67,
      and hematoxylin and eosin (H&E) were conducted on tumor samples for correlation
      with imaging results. RESULTS: CRLX101-treated tumors at day 2, 4, and 7
      posttreatment exhibited changes in mean ADC = 16 +/- 9%, 24 +/- 10%, 49 +/- 17%,
      and size (TV) = -5 +/- 3%, -30 +/- 4%, and -45 +/- 13%, respectively. Both
      parameters were statistically greater than controls [p(ADC) <= 0.02, and p(TV) <=
      0.01 at day 4 and 7], and noticeably greater than CPT-11-treated tumors (ADC = 5
      +/- 5%, 14 +/- 7%, and 18 +/- 6%; TV = -15 +/- 5%, -22 +/- 13%, and -26 +/- 8%).
      Model-derived parameters for cell proliferation obtained using ADC data
      distinguished CRLX101-treated tumors from controls (P = 0.02). CONCLUSIONS:
      Temporal changes in ADC specified early CRLX101 treatment response and could be
      used to model image-derived cell proliferation rates following treatment.
      Comparisons of targeted and nontargeted treatments highlight the utility of
      noninvasive imaging and modeling to evaluate, monitor, and predict responses to
      targeted nanotherapeutics.

PMID- 23532892
TI  - Inhibition of NF-kappaB-mediated signaling by the cyclin-dependent kinase
      inhibitor CR8 overcomes prosurvival stimuli to induce apoptosis in chronic
      lymphocytic leukemia cells.
AB  - PURPOSE: Chronic lymphocytic leukemia (CLL) is currently incurable with standard
      chemotherapeutic agents, highlighting the need for novel therapies. Overcoming
      proliferative and cytoprotective signals generated within the microenvironment of
      lymphoid organs is essential for limiting CLL progression and ultimately
      developing a cure. EXPERIMENTAL DESIGN: We assessed the potency of cyclin
      dependent kinase (CDK) inhibitor CR8, a roscovitine analog, to induce apoptosis
      in primary CLL from distinct prognostic subsets using flow cytometry-based
      assays. CLL cells were cultured in in vitro prosurvival and proproliferative
      conditions to mimic microenvironmental signals in the lymphoid organs, to
      elucidate the mechanism of action of CR8 in quiescent and proliferating CLL cells
      using flow cytometry, Western blotting, and quantitative real-time PCR. RESULTS:
      CR8 was 100-fold more potent at inducing apoptosis in primary CLL cells than
      roscovitine, both in isolated culture and stromal-coculture conditions.
      Importantly, CR8 induced apoptosis in CD40-ligated CLL cells and preferentially
      targeted actively proliferating cells within these cultures. CR8 treatment
      induced downregulation of the antiapoptotic proteins Mcl-1 and XIAP, through
      inhibition of RNA polymerase II, and inhibition of NF-kappaB signaling at the
      transcriptional level and through inhibition of the inhibitor of IkappaB kinase
      (IKK) complex, resulting in stabilization of IkappaBalpha expression.
      CONCLUSIONS: CR8 is a potent CDK inhibitor that subverts pivotal prosurvival and
      proproliferative signals present in the tumor microenvironment of CLL patient
      lymphoid organs. Our data support the clinical development of selective CDK
      inhibitors as novel therapies for CLL.

PMID- 23532893
TI  - Assessment of audit methodologies for bias evaluation of tumor progression in
      oncology clinical trials.
AB  - As progression-free survival (PFS) has become increasingly used as the primary
      endpoint in oncology phase III trials, the U.S. Food and Drug Administration
      (FDA) has generally required a complete-case blinded independent central review
      (BICR) of PFS to assess and reduce potential bias in the investigator or local
      site evaluation. However, recent publications and FDA analyses have shown a high
      correlation between local site evaluation and BICR assessments of the PFS
      treatment effect, which questions whether complete-case BICR is necessary. One
      potential alternative is to use BICR as an audit tool to detect evaluation bias
      in the local site evaluation. In this article, the performance characteristics of
      two audit methods proposed in the literature are evaluated on 26 prospective,
      randomized phase III registration trials in nonhematologic malignancies. The
      results support that a BICR audit to assess potential bias in the local site
      evaluation is a feasible approach. However, implementation and logistical
      challenges need further consideration and discussion.

PMID- 23532894
TI  - Improved survival with HPV among African Americans with oropharyngeal cancer.
AB  - PURPOSE: A major limitation of studies reporting a lower prevalence rate of human
      papilloma virus (HPV) in African American patients with oropharyngeal squamous
      cell cancer (OPSCC) than Caucasian Americans, with corresponding worse outcomes,
      was adequate representation of HPV-positive African American patients. This study
      examined survival outcomes in HPV-positive and HPV-negative African Americans
      with OPSCC. EXPERIMENTAL DESIGN: The study cohort of 121 patients with primary
      OPSCC had 42% African Americans. Variables of interest included age, race,
      gender, HPV status, stage, marital status, smoking, treatment, and date of
      diagnosis. RESULTS: Caucasian Americans are more likely to be HPV positive (OR =
      3.28; P = 0.035), as are younger age (age < 50 OR = 7.14; P = 0.023 compared with
      age > 65) or being married (OR = 3.44; P = 0.016). HPV positivity and being
      unmarried were associated with being late stage (OR = 3.10; P = 0.047 and OR =
      3.23; P = 0.038, respectively). HPV-negative patients had 2.7 times the risk of
      death as HPV-positive patients (P = 0.004). Overall, the HPV-race groups differed
      (log-rank P < 0.001), with significantly worse survival for HPV-negative African
      Americans versus (i) HPV-positive African Americans (HR = 3.44; P = 0.0012); (ii)
      HPV-positive Caucasian Americans (HR = 3.11; P = < 0.049); and (iii) HPV-negative
      Caucasian Americans (HR = 2.21; P = 0.049). CONCLUSIONS: HPV has a substantial
      impact on overall survival in African American patients with OPSCC. Among African
      American patients with OPSCC, HPV-positive patients had better survival than HPV
      negative. HPV-negative African Americans also did worse than both HPV-positive
      Caucasian Americans and HPV-negative Caucasian Americans. This study adds to the
      mounting evidence of HPV as a racially linked sexual behavior life style risk
      factor impacting survival outcomes for both African American and Caucasian
      American patients with OPSCC.

PMID- 23532895
TI  - Exogenous SPARC suppresses proliferation and migration of prostate cancer by
      interacting with integrin beta1.
AB  - BACKGROUND: The matricellular protein secreted protein acidic and rich in
      cysteine (SPARC) plays an important role on tumor metastasis and progression in
      several cancers. However, the roles of SPARC in prostate cancer (PCa) remain
      unclear. METHODS: To identify SPARC protein in prostate tissue,
      immunohistochemical analysis of SPARC was conducted using human prostate tissue
      microarray. To detect SPARC expression in prostate cancer (LNCaP, DU145, and PC
      3) and stromal cells, RT-PCR, western blot analysis, and ELISA was conducted. To
      reveal the function of exogenous SPARC in PCa cells, AKT phosphorylation was
      confirmed by western blot analysis after coculture with stromal cells.
      Proliferation and migration of PCa cells were examined by addition of SPARC. The
      interaction between SPARC and integrin beta1 was confirmed by western blot
      analysis after immunoprecipitation. RESULTS: SPARC protein was expressed well in
      normal tissue compared with PCa tissue. ELISA showed high secreted SPARC protein
      in normal prostate-derived stromal cell (PrSC) compared with PCa-derived stromal
      cell (PCaSC) and PCa. PCa cells cocultured with PrSC showed reduced AKT
      phosphorylation more than with PCaSC. PCa cells cocultured with PrSC whose SPARC
      was knocked-down restored AKT phosphorylation. Moreover, PCa cells treated with
      SPARC led to reduced AKT phosphorylation. Immunoprecipitation with SPARC revealed
      interaction of SPARC and integrin beta1 in PCa cells. Inhibited proliferation and
      migration of PCa cells by SPARC was restored by integrin beta1 neutralizing
      antibody. CONCLUSIONS: Reduced SPARC secretion from stromal cells might affect
      PCa progression mediating through limiting AKT phosphorylation after interaction
      with integrin beta1.

PMID- 23532896
TI  - Effects of pre-existing anti-carrier immunity and antigenic element multiplicity
      on efficacy of a modular virus-like particle vaccine.
AB  - Modularization of a peptide antigen for presentation on a microbially synthesized
      murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative
      for rapid and low-cost vaccine delivery at a global scale. In this approach,
      heterologous modules containing peptide antigenic elements are fused to and
      displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via
      ordered and densely repeated presentation of the modules. This study addresses
      two key engineering questions pertaining to this platform, exploring the effects
      of (i) pre-existing carrier-specific immunity on modular VLP vaccine
      effectiveness and (ii) increase in the antigenic element number per VLP on
      peptide-specific immune response. These effects were studied in a mouse model and
      with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen,
      J8i. The data presented here demonstrate that immunization with a modular VLP
      could induce high levels of J8i-specific antibodies despite a strong pre-existing
      anti-carrier immune response. Doubling of the J8i antigenic element number per
      VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the
      strategy, when used in conjunction with increased VLP dose, could effectively
      increase the peptide dose up to 10-fold, leading to a significantly higher J8i
      specific antibody titer. This study further supports feasibility of the MuPyV
      modular VLP vaccine platform by showing that, in the absence of adjuvant,
      modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to
      raise a high level of peptide-specific IgGs indicative of bactericidal activity.

PMID- 23532897
TI  - Impact of the proline residue on ligand binding of neurotensin receptor 2 (NTS2)
      selective peptide-peptoid hybrids.
AB  - To investigate the binding mode and structure-activity relationships (SARs) of
      selective neurotensin receptor 2 (NTS2) ligands, novel peptide-peptoid hybrids
      that simulate the function of the endogenous ligand were developed. Starting from
      our recently described NTS2 ligands of type 1, structural variants of type 2 and
      the metabolically stable analogues 3 a,b were developed. Replacement of the
      proline unit by a collection of structural surrogates and evaluation of the
      respective molecular probes for NTS2 affinity and selectivity indicated similar
      SARs as described for NT(8-13) derivatives bound to the subtype NTS1. Peptide
      peptoid hybrids 2 d, 3 a,b showed substantial NTS2 binding affinity (Ki =8.1-16
      nM) and 2400-8600-fold selectivity over NTS1. The thiazolidine derivative 3 b
      showed metabolic stability over 32 h in a serum degradation assay. In an inositol
      phosphate accumulation assay, the neurotensin mimetics 3 a and 3 b displayed an
      inhibition of constitutive activity exceeding 1.7-2.0 times the activity of NT(8
      13). The fluorinated derivative 3 a could afford attractive opportunities to
      detect NTS2 by (19) F magnetic resonance imaging.

PMID- 23532898
TI  - Bilateral pheochromocytomas, hemihyperplasia, and subtle somatic mosaicism: the
      importance of detecting low-level uniparental disomy.
AB  - We report on a patient with early onset pediatric bilateral pheochromocytomas
      caused by mosaic chromosome 11p15 paternal uniparental isodisomy (UPD).
      Hemihyperplasia of the arm was diagnosed in a 4-month-old female and clinical
      methylation testing for 11p15 in the blood was normal, with a reported detection
      threshold for mosaicism of 20%. She was subsequently diagnosed at 18 months with
      bilateral pheochromocytomas. Single-nucleotide polymorphism (SNP) array analysis
      of pheochromocytoma tissue demonstrated mosaic deletions of 8p12pter,
      21q21.1qter, 22q11.23qter; commonly seen in pheochromocytomas. In addition,
      mosaic 11p15.3pter homozygosity was noted. Molecular testing for other causes of
      pheochromocytomas was normal, suggesting that 11p15 homozygosity was the primary
      event. Subsequent SNP array analysis of skin fibroblasts from the hyperplastic
      side demonstrated 5% mosaic paternal UPD for 11p15. We have subsequently used SNP
      array analysis to identify four patients with subtle hemihyperplasia with low
      level mosaic UPD that was not detected by methylation analysis. Given the
      increased sensitivity of SNP array analysis to detect UPD along with the
      increased incidence of tumorigenesis in these UPD patients, we suggest that it
      has high utility in the clinical work-up of hemihyperplasia. The present case
      also suggests that 11p15 paternal UPD may be an under-detected mechanism of
      sporadic pheochromocytoma in the pediatric population. Furthermore, a review of
      the literature suggests that patients with 11p15 paternal UPD may present after 8
      years of age with pheochromocytoma and raises the possibility that ultrasound
      screening could be considered beyond 8 years of age in this subset of
      hemihyperplasia and Beckwith-Wiedemann syndrome patients.

PMID- 23532899
TI  - Lung manifestations in MPO-ANCA associated vasculitides in children.
AB  - OBJECTIVE: To describe lung manifestations in MPO-ANCA associated vasculitides in
      children. METHODS: We retrospectively reviewed the medical records of patients
      with MPO-ANCA associated vasculitis, who were followed in two pediatric
      nephrology departments from January 2000 to December 2010. RESULTS: Twelve
      patients were identified with MPO-ANCA over the study period. Their median age
      (IQR) at diagnosis was 10.5 (6.3-12.0) years, and their median duration of follow
      up was 4.8 (1.2-7.5) years. Only five of them had pulmonary involvement with
      diffuse alveolar hemorrhage. Lung involvement was inaugural for four of five
      children. One child with severe chronic respiratory disease and renal failure
      died after 6 years of disease progression. Pulmonary function tests were
      available for 10 children. They were within normal ranges in four of five
      patients without clinical lung manifestations, and no significant impairment was
      observed in children with pulmonary complications. CONCLUSIONS: Diffuse alveolar
      hemorrhage complicates 40% of cases of MPO-ANCA associated vasculitides in
      children with renal involvement. After an acute potentially severe phase, a
      complete recovery without significant functional impairment was observed in four
      of five affected children.

PMID- 23532900
TI  - New alternatives for minimally invasive management of uroliths: nephroliths.
AB  - Urolithiasis is a common clinical problem in small animal veterinary patients.
      Management of upper urinary tract calculi can be particularly challenging in
      small animals, as traditional surgical removal can be associated with significant
      morbidity. In humans, minimally invasive treatment options have replaced
      traditional surgical removal in many cases. This article reviews the current
      literature on the various types of lithotripsy and some of the newer minimally
      invasive options available for management of nephrolithiasis in small animal
      veterinary patients. An article in the January 2013 issue addressed management of
      lower urinary tract uroliths; a future article will discuss current management
      strategies for ureteroliths.

PMID- 23532901
TI  - Surgical views: Thoracoscopy: common techniques in small animals.
AB  - Thoracoscopy is gaining popularity in small animal surgery as an alternative to
      thoracotomy for an increasing variety of cases. This article discusses the
      details of some of the most frequently performed thoracoscopic procedures in
      small animal practice: diagnostic biopsy of pleural, mediastinal, pericardial,
      and lung tissue; thoracoscopic pericardial window creation and subphrenic
      pericardectomy; lung lobectomy; thoracic duct ligation; and cranial mediastinal
      mass resection. A companion article that presented the instrumentation,
      anesthesia challenges, and approaches for thoracoscopic procedures in small
      animals was published in the January 2013 issue.

PMID- 23532902
TI  - Tremorgenic mycotoxicosis in dogs.
AB  - Ingestion of tremorgenic mycotoxins formed in spoiled food can cause an acute
      tremor syndrome, the severity of which can range from mild to life-threatening.
      Swift recognition of the likely cause is required for accurate prognostication
      and rapid institution of appropriate therapy, which leads to complete resolution
      in most cases.

PMID- 23532903
TI  - Equine laparoscopy: gonadectomy.
AB  - Laparoscopic removal of the gonads from male and female horses is regularly
      performed for a variety of reasons. In female horses, common indications for
      ovariectomy include behavioral problems and signs of abdominal pain that are
      linked to estrus. Another indication is an abnormal, enlarged ovary, typically
      due to ovarian neoplasia, the most common being granulosa thecal cell tumor.
      Ovariectomy is also a treatment option for ovarian hematomas and other
      abnormalities. In addition, ovariectomy is used to sterilize mares intended for
      artificial insemination or embryo transfer programs.

PMID- 23532904
TI  - Excellence in exotics: Case report: urolithiasis in a female Guinea pig.
AB  - A 2-year-old, intact female guinea pig presented to the clinic for a history of
      squealing and straining to urinate for 2 days. The husbandry of this animal was
      acceptable, and the diet consisted of commercial alfalfa-based guinea pig
      pellets, alfalfa hay, a variety of vegetables, and a water-soluble vitamin C
      supplement.

PMID- 23532905
TI  - Excellence in exotics: Practice tip: ferret urinary tract catheterization.
AB  - In ferrets, urinary tract catheterization is most often indicated for neutered
      males with a urethral obstruction. Obstructions are commonly caused by prostatic
      enlargement secondary to adrenal tumor hormone production or, less commonly, by
      urolithiasis. A ferret with a urethral obstruction needs immediate intervention
      to relieve the obstruction.

PMID- 23532906
TI  - Mechanism to trigger unfolding in O(6) -alkylguanine-DNA alkyltransferase.
AB  - O(6) -alkylguanine-DNA alkyltransferase (AGT) adopts a non-enzymatic suicide
      mechanism for the repair of methylated guanine bases by transferring the methyl
      adduct to itself, thereby initiating unfolding and fast degradation. Classical
      molecular dynamics simulations provide quantitative evidence that two conserved
      glycine residues at the centre of an alpha-helix make the structure susceptible
      to structural perturbations. The stability of this helix, designated the
      "recognition helix", is an important factor during the early onset of unfolding
      of human AGT (hAGT). By combining theory and experiment, we found that helical
      stability is controlled by key factors in the surrounding protein structure. By
      using a "double-clip" mechanism, nearby residues hydrogen bond to both the base
      and centre of the helix. This double clip stabilises this site in the protein in
      the absence of substrate, but the helix is destabilised upon alkylation. The
      present investigation aimed to establish why alkylation of hAGT leads to
      conformational changes and how the protein environment functions as a switch,
      thus turning the stability of the protein "on" or "off" to tune degradability.

PMID- 23532907
TI  - ERP P1-N1 changes associated with Vernier perceptual learning and its location
      specificity and transfer.
AB  - Our recent studies demonstrate that perceptual learning can transfer completely
      to untrained retinal locations upon proper training procedures, which suggests
      perceptual learning being a high-level learning process occurring beyond the
      retinotopic visual areas. We propose that whether learning is location specific
      depends on the functional connections between high-level learning and the sensory
      inputs corresponding to the untrained retinal locations. These inputs may be
      suppressed by intensive training and focused (spatial) attention on the trained
      location to obstruct learning transfer. Here we present event-related potential
      (ERP) evidence that Vernier perceptual learning and its transfer are associated
      with P1 reduction and N1 enhancement. However, location specificity is only
      associated with N1 suppression corresponding to the untrained retinal location.
      These results are consistent with our proposal that the blockage of top-down
      influences or functional connections and the inhibition of visual inputs
      corresponding to untrained locations may contribute to location specificity in
      perceptual learning.

PMID- 23532908
TI  - Crowding of biological motion stimuli.
AB  - It is difficult to identify a target in the peripheral visual field when it is
      flanked by distractors. In the present study, we investigated this "crowding"
      effect for biological motion stimuli. Three walking biological motion stimuli
      were presented horizontally in the periphery with various distances between them,
      and observers reported the walking direction of the central figure. When the
      inter-walker distance was small, discriminating the direction became difficult.
      Moreover, the reported direction for the central target was not simply noisier,
      but reflected a degree of pooling of the three directions from the target and two
      flankers. However, when the two flanking distractors were scrambled walking
      biological motion stimuli, crowding was not seen. This result suggests that the
      crowding of biological motion stimuli occurs at a high-level of motion
      perception.

PMID- 23532909
TI  - Perception of second- and third-order orientation signals and their interactions.
AB  - Orientation signals, which are crucial to many aspects of visual function, are
      more complex and varied in the natural world than in the stimuli typically used
      for laboratory investigation. Gratings and lines have a single orientation, but
      in natural stimuli, local features have multiple orientations, and multiple
      orientations can occur even at the same location. Moreover, orientation cues can
      arise not only from pairwise spatial correlations, but from higher-order ones as
      well. To investigate these orientation cues and how they interact, we examined
      segmentation performance for visual textures in which the strengths of different
      kinds of orientation cues were varied independently, while controlling potential
      confounds such as differences in luminance statistics. Second-order cues (the
      kind present in gratings) at different orientations are largely processed
      independently: There is no cancellation of positive and negative signals at
      orientations that differ by 45 degrees . Third-order orientation cues are readily
      detected and interact only minimally with second-order cues. However, they
      combine across orientations in a different way: Positive and negative signals
      largely cancel if the orientations differ by 90 degrees . Two additional elements
      are superimposed on this picture. First, corners play a special role. When second
      order orientation cues combine to produce corners, they provide a stronger signal
      for texture segregation than can be accounted for by their individual effects.
      Second, while the object versus background distinction does not influence
      processing of second-order orientation cues, this distinction influences the
      processing of third-order orientation cues.

PMID- 23532910
TI  - Expression of HGF and Met in human tissues of colorectal cancers: biological and
      clinical implications for synchronous liver metastasis.
AB  - BACKGROUND AND AIMS: Synchronous liver metastasis (SLM) remains a significant
      problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte
      growth factor (HGF) and Met plays an important role in cancer invasion and
      metastasis and is being developed to be targeted drugs. We aimed to investigate
      the role of HGF/Met in SLM based on a case-matched study and comparison between
      primary tumors and matched metastases. METHODS: A group of 30 patients with SLM
      and other two groups of patients without SLM in a hospital database were
      collected. They were matched into according to clinicopathological factors. 81
      patients were included in the study. Their tissues of primary colorectal cancers,
      lymph nodes and liver metastases were collected to detect HGF and Met expression
      by immunohistochemistry and RT-PCR. RESULTS: Expression of HGF and Met at the
      protein level and the RNA level in primary CRCs with SLM were significantly
      higher than that in primary colorectal carcinomas without liver metastases (all P
      value<0.05). Their expression was only related to SLM when concurrent with
      regional lymph node metastasis (all P value<0.05) but had little influence on SLM
      without involvement of lymph node metastasis (all P value>0.05). Comparison their
      expression between primary tumors and matched metastases, major concordance and
      minor difference existed. CONCLUSIONS: HGF and Met may exert functions in the
      development of SLM when concurrent with lymph node metastases but had little
      influence on SLM without lymph node metastasis, further indicating their roles
      and potential values for a subtype of colorectal cancer metastasis. Major
      concordance and minor difference exist between primary tumors and matched
      metastases, which further provides evidence for evaluating the response to their
      inhibitors based on primary tumors or metastases.

PMID- 23532912
TI  - Report of a deaf child with Tourette's disorder.
AB  - This is a case study of a deaf child with Tourette's Disorder (TD). Hearing
      parents and mental health clinicians unfamiliar with typical behaviors of deaf
      children may have difficulties differentiating the clinical presentation of
      symptoms of TD from the effects of deafness, as well as in implementing
      appropriate interventions. This case study reports the history, symptoms,
      diagnostic process, and treatment interventions. This is relevant for furthering
      the clinical knowledge of mental health professionals working with Deaf, deaf,
      and hard-of-hearing children and adolescents.

PMID- 23532911
TI  - Metabolic reprogramming and validation of hyperpolarized 13C lactate as a
      prostate cancer biomarker using a human prostate tissue slice culture bioreactor.
AB  - BACKGROUND: The treatment of prostate cancer has been impeded by the lack of both
      clinically relevant disease models and metabolic markers that track tumor
      progression. Hyperpolarized (HP) (13) C MR spectroscopy has emerged as a new
      technology to investigate the metabolic shifts in prostate cancer. In this study,
      we investigate the glucose reprogramming using HP (13) C pyruvate MR in a patient
      derived prostate tissue slice culture (TSC) model. METHODS: The steady-state
      metabolite concentrations in freshly excised human prostate TSCs were assessed
      and compared to those from snap-frozen biopsy samples. The TSCs were then applied
      to a perfused cell (bioreactor) platform, and the bioenergetics and the dynamic
      pyruvate flux of the TSCs were investigated by (31) P and HP (13) C MR,
      respectively. RESULTS: The prostate TSCs demonstrated steady-state glycolytic and
      phospholipid metabolism, and bioenergetics that recapitulate features of prostate
      cancer in vivo. (13) C spectra following injection of HP (13) C pyruvate showed
      significantly increased pyruvate to lactate flux in malignant as compared to the
      benign prostate TSCs. This increased flux in the malignant prostate TSCs
      correlated with both increased expression of monocarboxylate transporters (MCT)
      and activity of lactate dehydrogenase (LDH). CONCLUSIONS: We provide the first
      mechanistic evidence for HP (13) C lactate as a prostate cancer biomarker in
      living human tissues, critical for the interpretation of in vivo studies. More
      broadly, the clinically relevant metabolic model system in combination with HP MR
      can facilitate the identification of clinically translatable biomarkers of
      prostate cancer presence, aggressiveness, and treatment response.

PMID- 23532913
TI  - Social anxiety in physical activity participation in patients with mental
      illness: a cross-sectional multicenter study.
AB  - BACKGROUND: Social anxiety (SA) is a frequent comorbid condition in patients with
      mental illness. However, no data exist regarding SA in physical activity (PA)
      situations. The aim of the present study was to measure the level of self
      reported SA in PA participation in patients with mental illness compared to
      healthy controls. METHODS: Six hundred ninety-three patients with mental illness
      and 2,888 controls aged between 18 and 65 years completed the Physical Activity
      and Sport Anxiety Scale (PASAS). Group and gender differences in PASAS scores
      were tested by ANOVA and Scheffe's post hoc test. RESULTS: After controlling for
      gender (P < .05), the patient group (men 40.2 +/- 14.4; women 49.2 +/- 17) scored
      higher on the PASAS compared to control group (men 30.6 +/- 12.2; women 37.3 +/-
      13.7). Within both groups, women reported higher levels of SA compared to men.
      CONCLUSIONS: Our data indicate that patients with mental illness reported higher
      levels of SA in PA situations compared to healthy control subjects. Health
      professionals should consider SA when trying to improve outcome and adherence of
      patients with mental illness to PA interventions.

PMID- 23532914
TI  - Fast and scalable purification of a therapeutic full-length antibody based on
      process crystallization.
AB  - The potential of process crystallization for purification of a therapeutic
      monoclonal IgG1 antibody was studied. The purified antibody was crystallized in
      non-agitated micro-batch experiments for the first time. A direct crystallization
      from clarified CHO cell culture harvest was inhibited by high salt
      concentrations. The salt concentration of the harvest was reduced by a simple
      pretreatment step. The crystallization process from pretreated harvest was
      successfully transferred to stirred tanks and scaled-up from the mL-scale to the
      1 L-scale for the first time. The crystallization yield after 24 h was 88-90%. A
      high purity of 98.5% was reached after a single recrystallization step. A 17-fold
      host cell protein reduction was achieved and DNA content was reduced below the
      detection limit. High biological activity of the therapeutic antibody was
      maintained during the crystallization, dissolving, and recrystallization steps.
      Crystallization was also performed with impure solutions from intermediate steps
      of a standard monoclonal antibody purification process. It was shown that process
      crystallization has a strong potential to replace Protein A chromatography. Fast
      dissolution of the crystals was possible. Furthermore, it was shown that
      crystallization can be used as a concentrating step and can replace several ultra
      /diafiltration steps. Molecular modeling suggested that a negative electrostatic
      region with interspersed exposed hydrophobic residues on the Fv domain of this
      antibody is responsible for the high crystallization propensity. As a result,
      process crystallization, following the identification of highly crystallizable
      antibodies using molecular modeling tools, can be recognized as an efficient,
      scalable, fast, and inexpensive alternative to key steps of a standard
      purification process for therapeutic antibodies.

PMID- 23532915
TI  - Network views for personalized medicine.
AB  - Clinical Proteomics has traveled a long way pinpointing potential biomarkers for
      a variety of diseases. However, the absence of clinical implementation of
      proteomics findings has led to a frank evaluation and reconsideration of applied
      practices in biomarker discovery, recruitment of technological tools for
      biomarker verification and generation of new guidelines for data reporting.
      Nevertheless, considering the need for vast clinical resources for biomarker
      validation, the frequent lack of clear definitions of contexts of use, in
      combination to the biomarker "high offer," progress toward biomarker
      implementation will even more require the adoption of an extensive open-minded
      approach: disease-focused networks are needed to ensure rapid exchange of
      information, initiation of appropriate studies, parallel validation of multiple
      biomarkers and sharing of valuable clinical resources. This viewpoint article
      targets to reflect on these issues and advocates the added value of
      multidisciplinary networks in biomarker development using bladder cancer as a
      paradigm.

PMID- 23532916
TI  - Salivary and serum analysis in children diagnosed with pneumonia.
AB  - The aim of the current study was to evaluate specific markers for pneumonia by
      using a non-invasive assessment of inflammatory/oxidative biomarkers in saliva
      accompanying a routine serum analysis. No study evaluating saliva of children
      with pneumonia has been published previously. Salivary analysis was performed in
      15 children diagnosed with lobar pneumonia and in a parallel group of 16 children
      matching in age and gender in whom there was no respiratory illness, and compared
      to the serum analysis obtained routinely in both groups of children. Salivary
      flow rate was lower in the patients' group as was uric acid concentration (by
      60%). Increase in salivary concentrations of almost all parameters analyzed was
      found: Ca, P, and Mg concentrations were higher in the patients' group by 23%,
      55%, and 33%, respectively, while LDH, total protein amylase and albumin
      concentrations were higher by 275%, 79%, and 42%, respectively. In the serum,
      white cell counts and neutrophils were significantly higher, and sodium level
      significantly lower in the patients' group. Compositional changes were in the
      range of 3-80% while the saliva alterations were more profound, in the range of
      42-275%. The results demonstrated in the current study indicate salivary analysis
      as a potentially novel tool for children with pneumonia. Human salivary
      collection and analysis is a non-invasive tool that could provide additional
      information for diagnosis and follow-up of pneumonia, especially in children.
      This is especially beneficial for pediatric patients, as salivary collection is
      simple, non-invasive, and patient-friendly.

PMID- 23532917
TI  - What is a complex chromosome rearrangement?

PMID- 23532918
TI  - Synthesis and in vitro characterisation of ifenprodil-based fluorescein
      conjugates as GluN1/GluN2B N-Methyl-D-aspartate receptor antagonists.
AB  - GluN2B-containing NMDA receptors are involved in many important physiological
      functions and play a pivotal role in mediating pain as well as in several
      neurodegenerative disorders. We aimed to develop fluorescent probes to target the
      GluN2B subunit selectively in order to allow better understanding of the
      relationships between receptor localisation and physiological importance.
      Ifenprodil, known as the GluNR2B antagonist of reference, was chosen as the
      template for the elaboration of probes. We had previously reported a fluorescein
      conjugate that was shown (by confocal microscopy imaging of DS-red-labelled
      cortical neurons) to bind specifically to GluN2B. To elaborate this probe, we
      explored the influence of both the nature and the attachment point of the spacer
      between the fluorophore and the parent compound, ifenprodil. We performed
      chemical modifications of ifenprodil at the benzylic position and on the phenol
      ring by introducing secondary amine or amide functions and evaluated alkyl chains
      from two to 20 bonds either including or not including secondary amide functions
      as spacers. The previously developed probe was found to display the greatest
      activity in the inhibition of NMDA-induced Ca(2+) influx by calcium imaging
      experiments on HEK293 cells transfected with the cDNA encoding for GluN1-1A and
      GluN2B. Further investigations revealed that this probe had a neuroprotective
      effect equivalent to that of ifenprodil in a standard test for neurotoxicity.
      Despite effects of lesser amplitude with these probes relative to ifenprodil, we
      demonstrated that they displaced [(3) H]ifenprodil in mouse brain slices in a
      similar manner.

PMID- 23532919
TI  - New alternatives for minimally invasive management of uroliths: ureteroliths.
AB  - Ureterolithiasis is a serious clinical problem in small animal veterinary
      medicine, and management can be challenging and frustrating. Various traditional
      surgical treatment options exist but are associated with significant morbidity
      and mortality. In humans, minimally invasive treatment options have overtaken
      traditional surgical removal. This article reviews the current literature on the
      management of ureteral stone disease, including various types of lithotripsy, and
      discusses some of the newer minimally invasive options available for small animal
      veterinary patients. It is important to realize that much of the data in this
      article is only published in abstract form and is largely one institution's
      experience with these novel techniques. Articles on minimally invasive management
      of lower urinary tract uroliths and nephroliths were published in the January
      2013 and February 2013 issues, respectively.

PMID- 23532920
TI  - Neurologic manifestations of hypothyroidism in dogs.
AB  - Hypothyroidism is a common endocrine disease in dogs. A variety of
      clinicopathologic abnormalities may be present; however, neurologic deficits are
      rare. In some instances, neurologic deficits may be the sole manifestation of
      hypothyroidism. Consequent ly, the diagnosis and management of the neurologic
      disorders associated with hypothyroidism can be challenging. This article
      describes several neurologic manifestations of primary hypothyroidism in dogs;
      discusses the pathophysiology of hypothyroidism-induced neurologic disorders
      affecting the peripheral and central nervous systems; and reviews the evidence
      for the neurologic effects of hypothyroidism.

PMID- 23532921
TI  - Focus on nutrition: Home-prepared diets for dogs and cats.
AB  - Promoting health and wellness in dogs and cats is a common goal for veterinarians
      and pet owners alike. Over the past decade, a number of highly publicized pet
      food recalls, as well as a growing awareness of the role of diet in health and
      disease for people, have changed the way some owners approach mealtime for their
      pets. Many owners, and some veterinarians, now advocate feeding dogs and cats
      home-prepared foods (raw, cooked, or both) as the sole source of nutrition for
      pets and cite either perceived health benefits or a general mistrust of the pet
      food industry as the reason. It is important for veterinary practitioners to
      understand the risks and benefits of home-prepared diets, as well as the
      motivation behind a pet owner's decision to follow this type of feeding regimen,
      to ensure optimal health for their patients.

PMID- 23532922
TI  - Canine inflammatory bowel disease: current and prospective biomarkers for
      diagnosis and management.
AB  - Inflammatory bowel disease (IBD) is a common gastrointestinal disorder of dogs.
      Current management strategies for this disease typically involve assessing the
      patient for resolution of clinical signs. Biologic markers that can be used to
      objectively assess the natural progression and predict the course of clinical
      disease, including response to treatment, are needed. Over the past 5 to 10
      years, there has been an ongoing search for a cost-effective, minimally invasive
      laboratory parameter that can detect disease activity and aid in monitoring
      treatment. This article reviews the biomarkers currently available for evaluating
      dogs with IBD.

PMID- 23532923
TI  - Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus
      infection.
AB  - CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a
      successful immune response and spontaneously clearing infection. Human leukocyte
      antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection
      of infected cells, and tapasin is an important component of the peptide loading
      complex for HLA class I. We sought to determine if tapasin polymorphisms affected
      the outcome of HCV infection. Patients with resolved or chronic HCV infection
      were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin
      gene. In a European, but not a US, Caucasian population, the tapasin G allele was
      significantly associated with the outcome of HCV infection, being found in 82.5%
      of resolvers versus 71.3% of persistently infected individuals (P = 0.02, odds
      ratio [OR] = 1.90 95% confidence interval [CI] = 1.11-3.23). This was more marked
      at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was
      protective (P < 0.03). Individuals with an HLA-B allele with an aspartate at
      residue 114 and the tapasin G allele were more likely to spontaneously resolve
      HCV infection (P < 0.00003, OR = 3.2 95% CI = 1.6-6.6). Additionally, individuals
      with chronic HCV and the combination of an HLA-B allele with an aspartate at
      residue 114 and the tapasin G allele also had stronger CD8+ T-cell responses (P =
      0.02, OR = 2.58, 95% CI-1.05-6.5). CONCLUSION: Tapasin alleles contribute to the
      outcome of HCV infection by synergizing with polymorphisms at HLA-B in a
      population-specific manner. This polymorphism may be relevant for peptide
      vaccination strategies against HCV infection.

PMID- 23532924
TI  - Sexual obsessions in pediatric obsessive-compulsive disorder: clinical
      characteristics and treatment outcomes.
AB  - BACKGROUND: Sexual obsessions are common in adults with obsessive-compulsive
      disorder (OCD), cause great distress, and are sometimes misinterpreted as
      indicating risk to others. Little is known about the prevalence, clinical
      correlates, and prognosis of such symptoms in young people. METHODS: Three
      hundred and eighty-three patients referred to a specialist pediatric OCD clinic
      were administered a series of measures at intake and, for those treated at the
      clinic, again after treatment. Patients with and without sexual obsessions were
      compared on socio-demographic and clinical characteristics. Mixed model analyses
      of variance compared treatment outcomes in both groups. RESULTS: A quarter of
      patients had sexual obsessions at baseline (age range 8-17); they had slightly
      more severe OCD symptoms and were more depressed than those without sexual
      obsessions. Aggressive and religious obsessions, magical thinking, fear of saying
      certain things, repeating rituals, superstitious games, mental rituals, and the
      need to tell, ask, or confess were more frequent in participants with sexual
      obsessions. Crucially, no differences in treatment outcome were found between the
      groups. CONCLUSIONS: Sexual obsessions are common in pediatric OCD, even in very
      young children. Although they may be associated with particular clinical
      features, they do not interfere with treatment response. The occurrence of sexual
      obsessions in children should be recognized and these symptoms understood as
      ordinary, nonthreatening OCD symptoms, which pose no risk to others. They respond
      to the standard treatment strategies, so children and families should receive the
      usual message of optimism regarding the chances of recovery.

PMID- 23532925
TI  - High-dose ibuprofen is not associated with increased biomarkers of kidney injury
      in patients with cystic fibrosis.
AB  - High-dose ibuprofen (IBU) may slow the decline of lung function in patients with
      cystic fibrosis (CF), but its use has been limited due to concerns over renal and
      gastrointestinal toxicity. In this pilot study, we examined the association of
      IBU with markers of acute kidney injury (AKI) in patients with CF. The effect of
      aminoglycoside (AG) exposure on AKI biomarkers was also examined. The AKI
      markers, kidney injury molecule-1 (KIM), N-acetyl-beta-glucosaminidase (NAG) and
      urine protein, normalized for creatinine, were chosen as they are more sensitive
      indicators of kidney injury than changes in serum creatinine. Urine samples from
      52 patients, 26 from patients who were treated with IBU, were analyzed. There was
      no significant association between IBU treatment and KIM-1, NAG or protein
      levels, compared to patients never treated with IBU. While there was an
      association between AG courses and KIM-1 levels, there were no differences in
      biomarker levels between IBU and non-IBU groups with respect to AG courses. These
      preliminary results suggest that IBU treatment in patients with CF may be safe
      with respect to renal toxicity.

PMID- 23532926
TI  - Model-based risk analysis of coupled process steps.
AB  - A section of a biopharmaceutical manufacturing process involving the enzymatic
      coupling of a polymer to a therapeutic protein was characterized with regards to
      the process parameter sensitivity and design space. To minimize the formation of
      unwanted by-products in the enzymatic reaction, the substrate was added in small
      amounts and unreacted protein was separated using size-exclusion chromatography
      (SEC) and recycled to the reactor. The quality of the final recovered product was
      thus a result of the conditions in both the reactor and the SEC, and a design
      space had to be established for both processes together. This was achieved by
      developing mechanistic models of the reaction and SEC steps, establishing the
      causal links between process conditions and product quality. Model analysis was
      used to complement the qualitative risk assessment, and design space and critical
      process parameters were identified. The simulation results gave an experimental
      plan focusing on the "worst-case regions" in terms of product quality and yield.
      In this way, the experiments could be used to verify both the suggested process
      and the model results. This work demonstrates the necessary steps of model
      assisted process analysis, from model development through experimental
      verification.

PMID- 23532928
TI  - Corpus callosum shape is altered in individuals with nonsyndromic cleft lip and
      palate.
AB  - Individuals with nonsyndromic cleft lip with or without cleft palate (CL/P) have
      altered brain structure compared with healthy controls. Preliminary evidence
      suggests that the corpus callosum may be dysmorphic in orofacial clefting;
      however, this midline brain structure has not been systematically assessed in
      this population. The goal of the present study was to carry out a morphometric
      assessment of the corpus callosum and its relationship to cognitive performance
      in a well-characterized patient cohort with orofacial cleft. Midline brain images
      were obtained from previously collected MRI scans of 24 CL/P subjects and 40
      adult-male controls. Eight landmarks on the corpus callosum were digitized on
      each image and their x,y coordinate locations saved. A geometric morphometrics
      analysis was applied to the landmark coordinate data to test for shape
      differences across groups. The relationship between corpus callosum shape and IQ
      was explored with nonparametric correlation coefficients. Results revealed
      significant differences in mean corpus callosum shape between CL/P cases and
      controls (P = 0.029). The CL/P corpus callosum was characterized by increased
      overall convexity resulting from a superior and posterior displacement. Within
      CL/P cases, increased corpus callosum shape dysmorphology was moderately
      correlated with reduced performance IQ (r = 0.546). These results provide
      additional evidence that midline brain changes may be an important part of the
      orofacial cleft phenotype.

PMID- 23532927
TI  - Using proteomics to uncover extracellular matrix interactions during cardiac
      remodeling.
AB  - The left ventricle (LV) responds to a myocardial infarction with an orchestrated
      sequence of events that result in fundamental changes to both the structure and
      function of the myocardium. This collection of responses is termed as LV
      remodeling. Myocardial ischemia resulting in necrosis is the initiating event
      that culminates in the formation of an extracellular matrix (ECM) rich infarct
      scar that replaces necrotic myocytes. While the cardiomyocyte is the major cell
      type that responds to ischemia, infiltrating leukocytes and cardiac fibroblasts
      coordinate the subsequent wound healing response. The matrix metalloproteinase
      family of enzymes regulates the inflammatory and ECM responses that modulate scar
      formation. Matridomics is the proteomic evaluation focused on ECM, while
      degradomics is the proteomic evaluation of proteases as well as their inhibitors
      and substrates. This review will summarize the use of proteomics to better
      understand matrix metalloproteinase roles in post myocardial infarction LV
      remodeling. 

PMID- 23532929
TI  - The addressing fragment of mitogaligin: first insights into functional and
      structural properties.
AB  - Mitogaligin is a mitochondrion-targeting protein involved in cell death. The
      sequence of the protein is unrelated to that of any known pro- or antiapoptotic
      protein. Mitochondrial targeting is controlled by an internal sequence from
      residues 31 to 53, and although this sequence is essential and sufficient to
      provoke cell death, the precise mechanism of action at the mitochondrial membrane
      remains to be elucidated. Here, by focusing on the [31-53] fragment, we first
      assessed and confirmed its cell cytotoxicity by microinjection. Subsequently,
      with the aid of membrane models, we evaluated the impact of the membrane
      environment on the 3D structure of the peptide and on how the peptide is embedded
      and oriented within membranes. The fragment is well organized, even though it
      does not contain a canonical secondary structure, and adopts an interfacial
      location. Structural comparison with other membrane-interacting Trp-rich peptides
      demonstrated similarities with the antimicrobial peptide tritrpcidin.

PMID- 23532931
TI  - Characterization and performance of short cationic antimicrobial peptide isomers.
AB  - Cationic antimicrobial peptides (CAMPs) represent an ancient defense mechanism
      against invading bacteria, with peptides such as the cathelicidins being
      essential elements of vertebrate innate immunity. CAMPs are typically associated
      with broad-spectrum antimicrobial potency and limited bacterial resistance. The
      cathelicidin identified from the elapid snake Naja atra (NA-CATH) contains a semi
      conserved repeated 11-residue motif (ATRA motif) with a sequence pattern
      consistent with formation of an amphipathic helical conformation. Short peptide
      amides (ATRA-1, -1A, -1P, and -2) generated based on the pair of ATRA motifs in
      NA-CATH exhibited varied antimicrobial potencies. The small size of the ATRA
      peptides, coupled with their varied antimicrobial performances, make them
      interesting models to study the impact various physico-chemical properties have
      on antimicrobial performance in helical CAMPs. Accordingly, the D- and L
      enantiomers of the peptide ATRA-1A, which in earlier studies had shown both good
      antimicrobial performance and strong helical character, were investigated in
      order to assess the impact peptide stereochemistry has on antimicrobial
      performance and interaction with chiral membranes. The ATRA-1A isomers exhibit
      varied potencies against four bacterial strains, and their conformational
      properties in the presence of mixed zwitterionic/anionic liposomes are influenced
      by anionic lipid content. These studies reveal subtle differences in the
      properties of the peptide isomers. Differences are also seen in the abilities of
      the ATRA-1A isomers to induce liposome fusion/aggregation, bilayer rearrangement
      and lysing through turbidity studies and fluorescence microscopy. The
      similarities and differences in the properties of the ATRA-1A isomers could aid
      in efforts to develop D-peptide-based therapeutics using high-performing L
      peptides as templates.

PMID- 23532930
TI  - Vaccine delivery using nanoparticles.
AB  - Vaccination has had a major impact on the control of infectious diseases.
      However, there are still many infectious diseases for which the development of an
      effective vaccine has been elusive. In many cases the failure to devise vaccines
      is a consequence of the inability of vaccine candidates to evoke appropriate
      immune responses. This is especially true where cellular immunity is required for
      protective immunity and this problem is compounded by the move toward devising
      sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such
      as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable
      nanospheres have received attention as potential delivery vehicles for vaccine
      antigens which can both stabilize vaccine antigens and act as adjuvants.
      Importantly, some of these nanoparticles (NPs) are able to enter antigen
      presenting cells by different pathways, thereby modulating the immune response to
      the antigen. This may be critical for the induction of protective Th1-type immune
      responses to intracellular pathogens. Their properties also make them suitable
      for the delivery of antigens at mucosal surfaces and for intradermal
      administration. In this review we compare the utilities of different NP systems
      for the delivery of sub-unit vaccines and evaluate the potential of these
      delivery systems for the development of new vaccines against a range of
      pathogens.

PMID- 23532932
TI  - Bioimaging real-time PXR-dependent mdr1a gene regulation in mdr1a.fLUC reporter
      mice.
AB  - The MDR1 gene encodes P-glycoprotein, a transmembrane drug efflux transporter
      that confers multidrug resistance in cancer cells and affects drug
      pharmacokinetics by virtue of its expression in the liver, kidney, and colon.
      Nuclear receptors human steroid and xenobiotic receptor (SXR) and constitutive
      androstane receptor (CAR) are possible master regulators of xenobiotic-inducible
      MDR1 expression in drug processing organs, but the mechanism of MDR1 regulation
      has yet to be directly demonstrated in vivo. Moreover, it has previously been
      impossible to determine the sustained or cumulative effect of repeated doses of
      xenobiotics on in vivo MDR1 expression. We previously reported a mouse model
      containing firefly luciferase (fLUC) knocked into the mdr1a genomic locus,
      allowing noninvasive bioimaging of intestinal mdr1a gene expression in live
      animals. In the current study, we crossed mdr1a.fLUC mice into the pxr knockout
      (pxr(-/-)) genetic background and injected mice with pregnenolone-16alpha
      carbonitrile (PCN), a strong mouse pregnane X receptor (PXR) ligand, and two
      therapeutically relevant taxanes, paclitaxel and docetaxel. All three agents
      induced mdr1a.fLUC expression (bioluminescence), but only PCN and docetaxel
      appeared to act primarily via PXR. Luminescence returned to baseline by 24-48
      hours after drug injection and was reinducible over two additional rounds of drug
      dosing in pxr(+/+) mice. TCPOBOP, a CAR ligand, modestly induced mdr1a.fLUC in
      pxr(+/+) and pxr(-/-) strains, consistent with CAR's minor role in mdr1a
      regulation. Collectively, these results demonstrate that the mdr1a.fLUC
      bioimaging model can capture changes in mdr1 gene expression under conditions of
      repeated xenobiotic treatment in vivo and that it can be used to probe the
      mechanism of gene regulation in response to different xenobiotic agents.

PMID- 23532933
TI  - Catharanthine dilates small mesenteric arteries and decreases heart rate and
      cardiac contractility by inhibition of voltage-operated calcium channels on
      vascular smooth muscle cells and cardiomyocytes.
AB  - Catharanthine is a constituent of anticancer vinca alkaloids. Its cardiovascular
      effects have not been investigated. This study compares the in vivo hemodynamic
      as well as in vitro effects of catharanthine on isolated blood vessels, vascular
      smooth muscle cells (VSMCs), and cardiomyocytes. Intravenous administration of
      catharanthine (0.5-20 mg/kg) to anesthetized rats induced rapid, dose-dependent
      decreases in blood pressure (BP), heart rate (HR), left ventricular blood
      pressure, cardiac contractility (dP/dt(max)), and the slope of the end-systolic
      pressure-volume relationship (ESPVR) curve. Catharanthine evoked concentration
      dependent decreases (I(max) >98%) in endothelium-independent tonic responses of
      aortic rings to phenylephrine (PE) and KCl (IC(50) = 28 uM for PE and IC(50) = 34
      uM for KCl) and of third-order branches of the small mesenteric artery (MA)
      (IC(50) = 3 uM for PE and IC(50) = 6 uM for KCl). Catharanthine also increased
      the inner vessel wall diameter (IC(50) = 10 uM) and reduced intracellular free
      Ca(2+) levels (IC(50) = 16 uM) in PE-constricted MAs. Patch-clamp studies
      demonstrated that catharanthine inhibited voltage-operated L-type Ca(2+) channel
      (VOCC) currents in cardiomyocytes and VSMCs (IC(50) = 220 uM and IC(50) = 8 uM,
      respectively) of MA. Catharanthine lowers BP, HR, left ventricular systolic blood
      pressure, and dP/dt(max) and ESPVR likely via inhibition of VOCCs in both VSMCs
      and cardiomyocytes. Since smaller vessels such as the third-order branches of MAs
      are more sensitive to VOCC blockade than conduit vessels (aorta), the primary
      site of action of catharanthine for lowering mean arterial pressure appears to be
      the resistance vasculature, whereas blockade of cardiac VOCCs may contribute to
      the reduction in HR and cardiac contractility seen with this agent.

PMID- 23532934
TI  - Smart applications for assessing minimal hepatic encephalopathy: novelty from the
      app revolution.

PMID- 23532935
TI  - Anxiety and 10-year risk of incident and recurrent depressive symptomatology in
      older adults.
AB  - BACKGROUND: Anxiety has been shown to often precede depression in children and
      young adults. Only a small number of investigations have examined this form of
      comorbidity in older adults and the temporal relationship of these syndromes
      remains unclear. The objective was to verify whether trait anxiety predicts
      incident/recurrent depressive symptomatology in older adults independently of
      variables susceptible to explain this relationship in this population, such as
      cognitive complaints, subjective health, and baseline depressive symptoms.
      METHODS: A random sample of 4,649 individuals aged 65 years or older from the
      Three-City Study, a prospective longitudinal study with a 10-year follow-up, was
      used. Incident and recurrent depressive symptomatology were determined by Center
      for Epidemiological Studies Depression Scale cutoff scores. Anxiety was measured
      using the trait scale of the State-Trait Anxiety Inventory. Cox proportional
      hazards models were used to determine the independent risk of depressive
      symptomatology for baseline anxiety, cognitive complaints, subjective health, and
      depressive symptoms, adjusting for sociodemographic, mental health, and physical
      health covariates. RESULTS: Incident depressive symptomatology was independently
      predicted by baseline anxiety, depressive symptoms, cognitive complaints, and
      subjective health. Recurrent depressive symptomatology was independently
      predicted by baseline anxiety and depressive symptoms, but not by cognitive
      complaints and subjective health. Anxiety was associated with a higher risk of
      incident depressive symptomatology only in participants without a history of a
      major depressive episode, and with a higher risk of recurrent depressive
      symptomatology in men than in women. CONCLUSIONS: Trait anxiety constitutes an
      important independent risk factor for subsequent depressive symptomatology in
      older adults.

PMID- 23532936
TI  - Reference values of exhaled nitric oxide in healthy children 1-5 years using off
      line tidal breathing.
AB  - Measurement of the fraction of exhaled nitric oxide (FeNO) is a useful test to
      diagnose and/or monitor eosinophilic airway inflammation. The off-line tidal
      breathing method is used for measurements in young children, but reference values
      for preschool children are scarce. The objective of this study was to establish
      reference values for FeNO in healthy children 1-5 years old. We included 51
      healthy children (23 males), mean age 32.5 months, from the general population
      and measured FeNO, using an off-line tidal breathing method with a
      chemiluminescence analyzer. The method proved feasible in 100% of the children.
      Geometric mean FeNO was 7.1 parts per billion (ppb), 95% confidence interval 2.8
      11.5 ppb, with the 95th percentile 22.6 ppb. No significant difference was found
      between boys and girls, and no correlations were observed between FeNO and age,
      height, or weight. This study demonstrates that the off-line tidal breathing
      method is feasible to measure FeNO in preschool children and provides reference
      values of FeNO in healthy children 1-5 years of age.

PMID- 23532937
TI  - Catalytic deoxydehydration of glycols with alcohol reductants.
AB  - Top shelf dehydration: Ammonium perrhenate catalysts combined with benzylic
      alcohol reductants are used for the efficient deoxydehydration of glycols to
      olefins. The olefin and aldehyde products can be easily separated and isolated.
      It is also demonstrated that the catalyst can be recovered and reused because of
      its low solubility in aromatic solvents.

PMID- 23532938
TI  - Prenatal presentation and diagnostic evaluation of suspected Smith-Lemli-Opitz
      (RSH) syndrome.
AB  - Smith-Lemli-Opitz (SLOS), or RSH syndrome, is an autosomal recessive deficiency
      of 7-dehydrocholesterol reductase (DHCR7) resulting in an accumulation of 7- and
      8-dehydrocholesterol (7- and 8-DHC) in tissues and body fluids. At birth patients
      have variable malformations of CNS, heart, kidney, genitalia, and limbs, which
      may be life-limiting. In later course, psychomotor and mental retardation and
      behavior abnormalities become evident. Prenatally SLOS can be suspected on the
      basis of malformations and intrauterine growth retardation (IUGR) in prenatal
      ultrasonography and reduced maternal free estriol in serum. The diagnosis is
      confirmed by sterol analysis in a chorionic villus biopsy or amniotic fluid (AF).
      In this study, we evaluated the predictive value of the above mentioned criteria
      in combination with family history by quantification of sterols in AF in
      pregnancies with either a family history, ultrasonographical abnormalities
      typical for SLOS, or reduced maternal serum unconjugated estriol (MSuE3). The
      relative frequency of SLOS in fetuses with an affected sibling was 0.23, as to be
      expected for an autosomal recessive disease. The probability for SLOS was <0.6%
      when neither an affected sib nor more than one typical SLOS malformation was
      present. For safety reasons and for cost-effectiveness we recommend careful
      evaluation of history, MSuE3, and clinical presentation before determining
      sterols in AF.

PMID- 23532939
TI  - Stabilization of enzymes in ionic liquids via modification of enzyme charge.
AB  - Due to the propensity of ionic liquids (ILs) to inactivate enzymes, the
      development of strategies to improve enzyme utility in these solvents is critical
      to fully exploit ILs for biocatalysis. We have developed a strategy to broadly
      improve enzyme utility in ILs based on elucidating the effect of charge
      modifications on the function of enzymes in IL environments. Results of stability
      studies in aqueous-IL mixtures indicated a clear connection between the ratio of
      enzyme-containing positive-to-negative sites and enzyme stability in ILs.
      Stability studies of the effect of [BMIM][Cl] and [EMIM][EtSO4 ] on chymotrypsin
      specifically found an optimum ratio of positively-charged amine-to-negatively
      charged acid groups (0.39). At this ratio, the half-life of chymotrypsin was
      increased 1.6- and 4.3-fold relative to wild-type chymotrypsin in [BMIM][Cl] and
      [EMIM][EtSO4 ], respectively. The half-lives of lipase and papain were similarly
      increased as much as 4.0 and 2.4-fold, respectively, in [BMIM][Cl] by modifying
      the ratio of positive-to-negative sites of each enzyme. More generally, the
      results of stability studies found that modifications that reduce the ratio of
      enzyme-containing positive-to-negative sites improve enzyme stability in ILs.
      Understanding the impact of charge modification on enzyme stability in ILs may
      ultimately be exploited to rationally engineer enzymes for improved function in
      IL environments.

PMID- 23532940
TI  - Highly efficient forster resonance energy transfer in a fast, serum-compatible
      immunoassay.
AB  - Highly efficient FRET leads to important enhancements for homogeneous
      immunoassays. By using the novel phosphorescent dye EuLH and BHQ-10 as a donor
      acceptor pair, the FRET efficiency increases to >99.5 %, leading to significantly
      improved signal-to-background ratio, precision and linear range. The
      phosphorescence detection enabled full compatibility to serum samples for this
      fast-responding immunoassay.

PMID- 23532941
TI  - Reply: To PMID 22806323.

PMID- 23532942
TI  - Public health benefits of weight loss: in response to Dixon et al.

PMID- 23532943
TI  - Biopolymers and the fellowship of DNA rings.
AB  - This article presents a brief account of the historical backdrop of the study of
      interlocked DNA rings (DNA catenanes), their formation in cells, and the
      importance of resolving the component rings of an intracellular DNA catenane if
      they are to be properly partitioned into a pair of progeny cells. In humans, for
      example, aberrant segregation of intertwined chromosomes is a major cause of
      birth defects, as well as termination of pregnancy in utero. Some yet unresolved
      issues of DNA catenation, including plausible structural and/or functional roles
      of DNA interlacing in chromosomes, are briefly mentioned.

PMID- 23532945
TI  - Kaposi sarcoma-associated herpesvirus g protein-coupled receptor enhances
      endothelial cell survival in part by upregulation of bcl-2.
AB  - BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) encoded G protein
      coupled receptor (vGPCR) is a constitutively active lytic phase protein with
      significant homology to the human interleukin-8 receptor. vGPCR is necessary and
      sufficient to induce angiogenesis as well as the spindle cell proliferation
      characteristic of Kaposi sarcoma (KS) lesions. We previously demonstrated that
      Bcl-2, an antiapoptotic protein, is upregulated in KS lesions. The aim of this
      study was to determine if vGPCR enhances endothelial cell survival through
      upregulation of Bcl-2 expression and to elucidate the signaling pathways
      involved. METHODS: Primary human umbilical vein endothelial cells were transduced
      with a recombinant retrovirus expressing vGPCR and then subjected to serum
      starvation. Cell viability and apoptosis were analyzed by fluorescence-activated
      cell sorting. Bcl-2 expression was determined by real-time quantitative reverse
      transcription polymerase chain reaction and immunoblotting. Specific
      pharmacological inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and the
      mammalian target of rapamycin (mTOR) were employed to elucidate the signaling
      pathways involved. Bcl-2 expression was knocked down using small interfering RNA
      (siRNA). RESULTS: Endothelial cells expressing vGPCR showed increased survival
      after serum starvation and upregulation of Bcl-2 messenger RNA (mRNA) and
      protein. The vGPCR-induced increases in both Bcl-2 mRNA and protein levels were
      dependent on PI3K signaling but not on mTOR. Moreover, siRNA inhibition of Bcl-2
      resulted in significant abrogation of the observed vGPCR-mediated cell survival
      advantage. CONCLUSIONS: Taken together, the results demonstrate that Bcl-2 is a
      mediator of vGPCR-induced endothelial cell survival and is a downstream effector
      of Akt in this process.

PMID- 23532946
TI  - Fraser syndrome: epidemiological study in a European population.
AB  - Fraser syndrome is a rare autosomal recessive disorder characterized by
      cryptophthalmos, cutaneous syndactyly, laryngeal, and urogenital malformations.
      We present a population-based epidemiological study using data provided by the
      European Surveillance of Congenital Anomalies (EUROCAT) network of birth defect
      registries. Between January 1990 and December 2008, we identified 26 cases of
      Fraser syndrome in the monitored population of 12,886,464 births (minimal
      estimated prevalence of 0.20 per 100,000 or 1:495,633 births). Most cases (18/26;
      69%) were registered in the western part of Europe, where the mean prevalence is
      1 in 230,695 births, compared to the prevalence 1 in 1,091,175 for the rest of
      Europe (P = 0.0003). Consanguinity was present in 7/26 (27%) families. Ten (38%)
      cases were liveborn, 14 (54%) pregnancies were terminated following prenatal
      detection of a serious anomaly, and 2 (8%) were stillborn. Eye anomalies were
      found in 20/24 (83%), syndactyly in 14/24 (58%), and laryngeal anomalies in 5/24
      (21%) patients. Ambiguous genitalia were observed in 3/24 (13%) cases. Bilateral
      renal agenesis was present in 12/24 (50%) and unilateral in 4/24 (17%) cases. The
      frequency of anorectal anomalies was particularly high (42%). Most cases of
      Fraser syndrome (85%) are suspected prenatally, often due to the presence of the
      association of renal agenesis and cryptophthalmos. In the European population, a
      high proportion (82%) of pregnancies is terminated, thus reducing the live birth
      prevalence to a third of the total prevalence rate.

PMID- 23532944
TI  - Long-term outcome in adults with obsessive-compulsive disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic condition that often
      produces lifelong morbidity, but few studies have examined long-term outcome
      (greater than 5 years) in adult patients. Available studies suggest that 32-74%
      of adult OCD patients will experience clinical improvement over the long term.
      However, these studies were conducted before validated OCD rating scales were
      established and the development of evidence-based treatments for OCD. METHODS: We
      investigated the 10-20 year outcome of 83 of 165 eligible subjects previously
      enrolled after participation in placebo-controlled trials of serotonin reuptake
      inhibitor (SRI) medications for OCD. We examined the association between clinical
      characteristics at initial assessment and OCD symptom severity at follow-up. We
      hypothesized that primary OCD symptom dimension and initial response to
      pharmacotherapy with serotonin reuptake inhibitors would be associated with later
      symptom severity. RESULTS: Only 20% (17 of 83) of subjects had experienced a
      remission of their OCD symptoms at follow-up (Y-BOCS <= 8). Forty-nine percent
      (41 of 83) of subjects were still experiencing clinically significant OCD
      symptoms. Response to initial SRI pharmacotherapy was significantly associated
      with long-term outcome: 31% (13 of 42) of subjects who responded (CGI < 3) to
      initial SRI pharmacotherapy were remitted at follow-up, compared to 12% (3 of 25)
      of partial responders and none of the 16 subjects who had no response to initial
      SRI pharmacotherapy. We did not find a significant association between long-term
      clinical outcome and any of the OCD symptom dimensions. CONCLUSION: Despite the
      introduction and dissemination of several evidence-based treatments for OCD, most
      adult OCD patients do not achieve remission. Initial response to pharmacotherapy
      was strongly associated with long-term outcome.

PMID- 23532947
TI  - Seroepidemiological study of chagas disease in the southern Amazon region of
      ecuador.
AB  - To determine the extent of Trypanosoma cruzi infection and/or transmission in the
      southern Amazon region of Ecuador, three indigenous communities in the provinces
      of Pastaza and Morona Santiago were serosurveyed. Chagatest(TM),
      Immunocomb((r))II and immunofluorescent (IF) assays were used. Among the 385
      inhabitants examined, nine (2.34%) were seropositive for T. cruzi infection. Of
      the nine positive sera, four (44.4%) fall in the 10-19, one each in the 20-29, 30
      39 and 40-49, and two in the 50-59 age groups. These results suggested the
      possible existence of an autochthonous active T. cruzi transmission in the region
      and provide the first serological evidence for T. cruzi infection in the southern
      province of Morona Santiago bordering Peru. Further studies are needed in these
      Amazonian provinces to ascertain the spread of T. cruzi infection in the area.

PMID- 23532948
TI  - C-C cross-coupling of primary and secondary benzylic alcohols using supported
      gold-based bimetallic catalysts.
AB  - Clean alcohol-alcohol cross-coupling: A clean and efficient one-pot direct C-C
      cross-coupling of equimolar amounts of primary and secondary alcohols by a facile
      hydrogen autotransfer pathway is achieved over a robust and easily recovered
      hydrotalcite-supported Au-Pd bimetallic catalyst system. A variety of primary and
      secondary alcohols have been selectively converted into the corresponding beta
      alkylated ketones in good yields.

PMID- 23532949
TI  - Nucleobase protection strategy for gene cloning and expression.
AB  - Protecting group chemistry meets molecular biology: Chemically modified dATP
      carrying a bulky triethylsilylethynyl group was used in a PCR-based synthesis of
      a gene internally protected against cleavage by restriction endonucleases. The
      unmodified flanking regions were cleaved for cloning into a plasmid which was
      replicated by E. coli, and used for protein production.

PMID- 23532951
TI  - The development of end- and beginning-state comfort in a cup manipulation task.
AB  - End-state comfort (ESC) is the tendency to assume comfortable postures at the end
      of simple object manipulation rather than at the start; and therefore has been
      used to assess the behavioral effects of motor planning. Adult-like patterns have
      been observed at age 9. Observations can extend to joint-action, such that adults
      consider the beginning-state comfort (BSC) of another, without sacrificing ESC;
      however, trends in children have yet to be delineated. This study investigated
      the development of ESC and BSC in a cup manipulation task. Three to 12-year-olds
      and adults were asked to pick up a cup and (1) pour a glass of water or (2) pass
      it to the researcher to pour. Paralleling previous findings, adult-like patterns
      of ESC were observed at age 9. Adding to the literature, adult-like evidence of
      BSC emerged at the age of 7. Therefore, 7-year-olds consider another's BSC;
      however, cannot facilitate ESC until age 9.

PMID- 23532950
TI  - Clonality, activated antigen-specific CD8(+) T cells, and development of
      autoimmune cholangitis in dnTGFbetaRII mice.
AB  - There are several murine models described with features similar to human primary
      biliary cirrhosis (PBC). Among these models, the one which has the closest
      serologic features to PBC is a mouse with a T-cell-restricted expression of the
      dominant negative transforming growth factor beta receptor type II
      (dnTGFbetaRII). Our work has demonstrated that CD8(+) T cells from dnTGFbetaRII
      mice transfer autoimmune cholangitis to Rag1(-/-) recipients. However, it
      remained unclear whether the autoimmune cholangitis was secondary to an intrinsic
      function within CD8(+) T cells or due to the abnormal TGFbetaR environment within
      which CD8(+) T cells were generated. To address this mechanistic issue, we used
      our dnTGFbetaRII, OT-I/Rag1(-/-) , OT-II/Rag1(-/-) mice and in addition generated
      OT-I/dnTGFbetaRII/Rag1(-/-) , and OT-II/dnTGFbetaRII/Rag1(-/-) mice in which the
      entire T-cell repertoire was replaced with ovalbumin (OVA)-specific CD8(+) or
      CD4(+) T cells, respectively. Importantly, neither the parental OT
      I/dnTGFbetaRII/Rag1(-/-) mice and/or OT-II/dnTGFbetaRII/Rag1(-/-) mice developed
      cholangitis. However, adoptive transfer demonstrated that only transfer of CD8(+)
      T cells from dnTGFbetaRII mice but not CD8(+) T cells from OT-I/Rag1(-/-) mice or
      from OT-I/dnTGFbetaRII/Rag1(-/-) mice transferred disease. These data were not
      secondary to an absence of CD4(+) T cell help since a combination of CD8(+) T
      cells from OT-I/dnTGFbetaRII/Rag1(-/-) and CD4(+) T cells from OT
      II/dnTGFbetaRII/Rag1(-/-) or CD8(+) T cells from OT-I/dnTGFbetaRII/Rag1(-/-) with
      CD4(+) T cells from OT-II/Rag1(-/-) mice failed to transfer disease. CONCLUSION:
      Defective TGFbetaRII signaling, in addition to clonal CD8(+) T cells that target
      biliary cells, are required for induction of autoimmune cholangitis.

PMID- 23532952
TI  - Ultrasound-mediated gene delivery systems by AG73-modified Bubble liposomes.
AB  - Targeted gene delivery to neovascular vessels in tumors is considered a promising
      strategy for cancer therapy. We previously reported that "Bubble liposomes"
      (BLs), which are ultrasound (US) imaging gas-encapsulating liposomes, were
      suitable for US imaging and gene delivery. When BLs are exposed to US, the bubble
      is destroyed, creating a jet stream by cavitation, and resulting in the
      instantaneous ejection of extracellular plasmid DNA (pDNA) or other nucleic acids
      into the cytosol. We developed AG73 peptide-modified Bubble liposomes (AG73-BL)
      as a targeted US contrast agent, which was designed to attach to neovascular
      tumor vessels and to allow specific US detection of angiogenesis (Negishi et al.,
      Biomaterials 2013, 34, 501-507). In this study, to evaluate the effectiveness of
      AG73-BL as a gene delivery tool for neovascular vessels, we examined the gene
      transfection efficiency of AG73-BL with US exposure in primary human endothelial
      cells (HUVEC). The transfection efficiency was significantly enhanced if the AG73
      BL attached to the HUVEC was exposed to US compared to the BL-modified with no
      peptide or scrambled peptide. In addition, the cell viability was greater than
      80% after transfection with AG73-BL. These results suggested that after the
      destruction of the AG73-BL with US exposure, a cavitation could be effectively
      induced by the US exposure against AG73-BL binding to the cell surface of the
      HUVEC, and the subsequent gene delivery into cells could be enhanced. Thus, AG73
      BL may be useful for gene delivery as well as for US imaging of neovascular
      vessels.

PMID- 23532953
TI  - Effects of seasonal snow on the growing season of temperate vegetation in China.
AB  - Variations in seasonal snowfall regulate regional and global climatic systems and
      vegetation growth by changing energy budgets of the lower atmosphere and land
      surface. We investigated the effects of snow on the start of growing season (SGS)
      of temperate vegetation in China. Across the entire temperate region in China,
      the winter snow depth increased at a rate of 0.15 cm yr(-1) (P = 0.07) during the
      period 1982-1998, and decreased at a rate of 0.36 cm yr(-1) (P = 0.09) during the
      period 1998-2005. Correspondingly, the SGS advanced at a rate of 0.68 day yr(-1)
      (P < 0.01) during 1982-1998, and delayed at a rate of 2.13 day yr(-1) (P = 0.07)
      during 1998-2005, against a warming trend throughout the entire study period of
      1982-2005. Spring air temperature strongly regulated the SGS of both deciduous
      broad-leaf and coniferous forests, whereas the winter snow had a greater impact
      on the SGS of grassland and shrubs. Snow depth variation combined with air
      temperature contributed to the variability in the SGS of grassland and shrubs, as
      snow acted as an insulator and modulated the underground thermal conditions. In
      addition, differences were seen between the impacts of winter snow depth and
      spring snow depth on the SGS; as snow depths increased, the effect associated
      went from delaying SGS to advancing SGS. The observed thresholds for these
      effects were snow depths of 6.8 cm (winter) and 4.0 cm (spring). The results of
      this study suggest that the response of the vegetation's SGS to seasonal snow
      change may be attributed to the coupling effects of air temperature and snow
      depth associated with the underground thermal conditions.

PMID- 23532954
TI  - The fibroblast growth factor receptor 2 p.Ala172Phe mutation in Pfeiffer syndrome
      -history repeating itself.
AB  - Pfeiffer syndrome is an autosomal dominant condition classically combining
      craniosynostosis with digital anomalies of the hands and feet. The majority of
      cases are caused by heterozygous mutations in the third immunoglobulin-like
      domain (IgIII) of FGFR2, whilst a small number of cases can be attributed to
      mutations outside this region of the protein. A mild form of Pfeiffer syndrome
      can rarely be caused by a specific mutation in FGFR1. We report on the clinical
      and genetic findings in a three generation British family with Pfeiffer syndrome
      caused by a heterozygous missense mutation, p.Ala172Phe, located in the IgII
      domain of FGFR2. This is the first reported case of this particular mutation
      since Pfeiffer's index case, originally described in a German family in 1964, on
      which basis the syndrome was eponymously named. Genetic analysis demonstrated the
      two families to be unrelated. Similarities in phenotypes between the two families
      are discussed. Independent genetic origins, but phenotypic similarities in the
      two families add to the evidence supporting the theory of selfish spermatogonial
      selective advantage for this rare gain-of-function FGFR2 mutation.

PMID- 23532955
TI  - Fluorescence quenching over short range in a donor-DNA-acceptor system.
AB  - A new donor-DNA-acceptor system has been synthesized containing Nile red-modified
      2'-deoxyuridine as charge donor and 6-N,N-dimethylaminopyrene-modified 2'
      deoxyuridine as acceptor to investigate the charge transfer in DNA duplexes using
      fluorescence spectroscopy and time-resolved femtosecond pump-probe techniques.
      Fluorescence quenching experiments revealed that the quenching efficiency of Nile
      red depends on two components: 1) the presence of a charge acceptor and 2) the
      number of intervening CG and AT base pairs between donor and acceptor.
      Surprisingly, the quenching efficiency of two base pairs (73% for CG and the same
      for AT) is higher than that for one base pair (68% for CG and 37% for AT), while
      at a separation of three base pairs less than 10% quenching is observed. A
      comparison with the results of time-resolved measurements revealed a correlation
      between quenching efficiency and the first ultrafast time constant suggesting
      that quenching proceeds via a charge transfer from the donor to the acceptor. All
      transients are satisfactorily described with two decays: a rapid charge transfer
      with 600 fs (~10(12) s(-1)) that depends strongly and in a non-linear fashion on
      the distance between donor and acceptor, and a slower time constant of a few
      picoseconds (~10(11) s(-1)) with weak distance dependence. A third time constant
      on a nanosecond time scale represents the fluorescence lifetime of the donor
      molecule. According to these results and time-dependent density functional theory
      (TDDFT) calculations a combination of single-step superexchange and multistep
      hopping mechanisms can be proposed for this short-range charge transfer.
      Furthermore, significantly less quenching efficiency and slower charge transfer
      rates at very short distances indicate that the direct interaction between donor
      and acceptor leads to a local structural distortion of DNA duplexes which may
      provide some uncertainty in identifying the charge transfer rates in short-range
      systems.

PMID- 23532956
TI  - Chemoselective CaO-mediated acylation of alcohols and amines in 2
      methyltetrahydrofuran.
AB  - Calcium oxide is proposed as an innocuous acid scavenger for the chemoselective
      synthesis of amide- and ester-type compounds. Although these molecules have wide
      spread applications in organic and pharmaceutical chemistry, and a large number
      of routes have been designed for their synthesis, the development of more
      efficient and environmentally friendly acylation strategies remains an ongoing
      challenge. The use of CaO allows for the stoichiometric acylation of primary
      alcohols in the presence of phenols or tertiary alcohols; amines can also be
      subjected to acylation reactions in the presence of hydroxyl groups. Chirality is
      obtained through acylation if the starting material is an optically pure alcohol
      or if a chiral acylating agent is used. Furthermore, the use of 2
      methyltetrahydrofuran (2-MeTHF), a more ecofriendly solvent, leads to maximized
      yields. This protocol is successfully applied to the synthesis of an interesting
      N-aryloxazolidin-2-one intermediate for the preparation of linezolid-type
      compounds.

PMID- 23532957
TI  - Transfer of spatial search between environments in human adults and young
      children (Homo sapiens): implications for representation of local geometry by
      spatial systems.
AB  - Whether animals represent environmental geometry in a global and/or local way has
      been the subject of recent debate. We applied a transfer of search paradigm
      between rectangular- and kite-shaped arenas to examine the performance of human
      adults (using virtual environments) and children of 2.5-3.5 years (using real
      arenas). Adults showed robust transfer to a congruent corner in a kite-shaped
      arena, following training in a rectangular-shaped arena in two paradigms modeled
      on those used with rats and young children respectively. In contrast, the
      children showed no evidence of transfer of search, despite above chance
      performance in the rectangular arena, and above chance performance in a study
      where search occurred in the kite arena only. The pattern of findings suggests
      global aspects of environmental geometry may be used to re-establish heading, and
      that the matching of elements of local geometry in new global contexts may be an
      advanced developmental achievement.

PMID- 23532958
TI  - Chronic plus binge ethanol feeding synergistically induces neutrophil
      infiltration and liver injury in mice: a critical role for E-selectin.
AB  - Chronic plus binge ethanol feeding acts synergistically to induce liver injury in
      mice, but the mechanisms underlying this phenomenon remain unclear. Here, we show
      that chronic plus binge ethanol feeding synergistically up-regulated the hepatic
      expression of interleukin-1beta and tumor necrosis factor alpha and induced
      neutrophil accumulation in the liver, compared with chronic or binge feeding
      alone. In vivo depletion of neutrophils through administration of an anti-Ly6G
      antibody markedly reduced chronic-binge ethanol feeding-induced liver injury.
      Real-time polymerase chain reaction analyses revealed that hepatic E-selectin
      expression was up-regulated 10-fold, whereas expression of other neutrophil
      infiltration-related adhesion molecules (e.g., P-selectin, intercellular adhesion
      molecule 1, and vascular cell adhesion molecule 1) was slightly up- or down
      regulated in this chronic-binge model. The genetic deletion of E-selectin
      prevented chronic-binge ethanol-induced hepatic neutrophil infiltration as well
      as elevation of serum transaminases without affecting ethanol-induced steatosis.
      In addition, E-selectin-deficient mice showed reduced hepatic expression of
      several proinflammatory cytokines, chemokines, and adhesion molecules, compared
      to wild-type mice, after chronic-binge ethanol feeding. Finally, the expression
      of E-selectin was highly up-regulated in human alcoholic fatty livers, but not in
      alcoholic cirrhosis. CONCLUSIONS: Chronic-binge ethanol feeding up-regulates
      expression of proinflammatory cytokines, followed by the induction of E-selectin.
      Elevated E-selectin plays an important role in hepatic neutrophil infiltration
      and injury induced by chronic-binge feeding in mice and may also contribute to
      the pathogenesis of early stages of human alcoholic liver disease.

PMID- 23532960
TI  - Analysis of de novo HOXA13 polyalanine expansions supports replication slippage
      without repair in their generation.
AB  - Polyalanine repeat expansion diseases are hypothesized to result from unequal
      chromosomal recombination, yet mechanistic studies are lacking. We identified two
      de novo cases of hand-foot-genital syndrome (HFGS) associated with polyalanine
      expansions in HOXA13 that afforded rare opportunities to investigate the
      mechanism. The first patient with HFGS was heterozygous for a de novo nine codon
      polyalanine expansion. Haplotype investigation showed that the expansion arose on
      the maternally inherited chromosome but not through unequal crossing over between
      homologs, leaving unequal sister chromatid exchange during mitosis or meiosis or
      slipped mispairing as possible explanations. The asymptomatic father of the
      second patient with HFGS was mosaic for a six codon polyalanine expansion.
      Multiple tissue PCR and clonal analysis of paternal fibroblasts showed only
      expansion/WT and WT/WT clones, and haplotype data showed that two unaffected
      offspring inherited the same paternal allele without the expansion, supporting a
      postzygotic origin. Absence of the contracted allele in the mosaic father does
      not support sister chromatid exchange in the origin of the expansion. Mosaicism
      for HOXA13 polyalanine expansions may be associated with a normal phenotype,
      making examination of parental DNA essential in apparently de novo HFGS cases to
      predict accurate recurrence risks. We could not find an example in the literature
      where unequal sister chromatid exchange has been proven for any polyalanine
      expansion, suggesting that the principal mechanism for polyalanine expansions
      (and contractions) is slipped mispairing without repair or that the true
      frequency of unequal sister chromatid exchange involving these repeats is low.

PMID- 23532959
TI  - Risk factors of treatment failure in diabetic foot ulcer patients.
AB  - BACKGROUND: Some diabetic feet heal without complication, but others undergo
      amputation due to progressive wounds. This study investigates the risk factors
      for amputation of diabetic feet. METHODS: A total of 55 patients who visited our
      institution from 2008 to 2012 were included in the study. The patients with
      abnormal fasting blood sugar levels, lower leg vascularity, and poor nutrition
      were excluded from the study group, and the wound states were unified. The
      patients were categorized into a treatment success group (n=47) and a treatment
      failure group (n=8), and their hemoglobin A1C (HgA1C), C-reactive protein (CRP),
      white blood cell count (WBC), and serum creatinine levels were analyzed. RESULTS:
      The initial CRP, WBC, and serum creatinine levels in the treatment failure group
      were significantly higher than that of the treatment success group, and the
      initial HgA1C level was significantly higher in the treatment success group. The
      CRP and WBC levels of both groups changed significantly as time passed, but their
      serum creatinine levels did not. CONCLUSIONS: The initial CRP, WBC, and serum
      creatinine levels were considered to be risk factors for amputation. Among them,
      the serum creatinine level was found to be the most important predictive risk
      factor. Because serum creatinine represents the renal function, thorough care is
      needed for the feet of diabetic patients with renal impairment.

PMID- 23532962
TI  - Theoretical shaping of femtosecond laser pulses for ultrafast molecular photo
      dissociation with control techniques based on time-dependent density functional
      theory.
AB  - The combination of time-dependent density functional theory and quantum optimal
      control formalism is used to optimize the shape of ultra-short laser pulses in
      order to achieve the photodissociation of the hydrogen molecule. The very short
      pulse durations used in this work (a few femtoseconds) do not allow for
      significant nuclear movement during irradiation, and thus the dissociation
      mechanism is sequential. During pulse irradiation, a large sudden momentum is
      communicated which can be understood in terms of population of excited, bound or
      unbound, dissociative electronic states. The target is defined in terms of the
      average opposing force during the action of the pulse, or equivalently, in terms
      of the final dissociative velocity.

PMID- 23532963
TI  - Mutual interaction between YAP and CREB promotes tumorigenesis in liver cancer.
AB  - Yes-associated protein (YAP), the downstream effecter of the Hippo-signaling
      pathway as well as cyclic adenosine monophosphate response element-binding
      protein (CREB), has been linked to hepatocarcinogenesis. However, little is known
      about whether and how YAP and CREB interact with each other. In this study, we
      found that YAP-CREB interaction is critical for liver cancer cell survival and
      maintenance of transformative phenotypes, both in vitro and in vivo. Moreover,
      both CREB and YAP proteins are highly expressed in a subset of human liver cancer
      samples and are closely correlated. Mechanistically, CREB promotes YAP
      transcriptional output through binding to -608/-439, a novel region from the YAP
      promoter. By contrast, YAP promotes protein stabilization of CREB through
      interaction with mitogen-activated protein kinase 14 (MAPK14/p38) and beta
      transducin repeat containing E3 ubiquitin protein ligase (BTRC). Gain-of-function
      and loss-of-function studies demonstrated that phosphorylation of CREB by
      MAPK14/p38 at ser133 ultimately leads to its degradation. Such effects can be
      enhanced by BTRC through phosphorylation of MAPK14/p38 at Thr180/Tyr182. However,
      YAP negatively controls phosphorylation of MAPK14/p38 through inhibition of BTRC
      expression. CONCLUSION: There is a novel positive autoregulatory feedback loop
      underlying the interaction between YAP and CREB in liver cancer, suggesting that
      YAP and CREB form a nexus to integrate the protein kinase A, Hippo/YAP, and
      MAPK14/p38 pathways in cancer cells and thus may be helpful in the development of
      effective diagnosis and treatment strategies against liver cancer.

PMID- 23532964
TI  - Latent inhibition of a conditioned taste aversion in fetal rats.
AB  - The etiology of schizophrenia's cognitive symptoms may have its basis in prenatal
      alterations of glutamate N-methyl-D-aspartate (NMDA) receptor functioning.
      Therefore, the current study investigated the effects of ketamine (an NMDA
      receptor blocking drug) on both a conditioned taste aversion (CTA) and latent
      inhibition (LI; a model of attentional capacity) in rat fetuses. We first sought
      to determine if a CTA could be diminished by nonreinforced preexposure to a CS in
      fetal rats (i.e., LI). We injected E18 pregnant Sprague-Dawley rats with 100%
      allicin (garlic taste) or an equal volume of saline. Some of the pregnant dams
      also received ketamine (100 mg/kg, i.p.). One day later (E19), the dams received
      a second injection of the CS, followed by either lithium chloride (the US) or
      saline. Finally, on E21 pups received oral lavage with allicin and observations
      of ingestive orofacial motor responses were recorded. When allicin had been
      paired with LiCl in utero, E21 fetuses exhibited a conditioned suppression of
      orofacial movements, indicative of an aversion to this taste. Preexposure to the
      garlic taste on E18 produced a LI of this CTA. Ketamine significantly disrupted
      the formation of the CTA and had some impact on LI. However, the direct effect of
      ketamine on LI is less certain since the drug also blocked the original CTA.

PMID- 23532965
TI  - Familial microdeletion of 17q24.3 upstream of SOX9 is associated with isolated
      Pierre Robin sequence due to position effect.
AB  - Pierre Robin sequence (PRS) is a malformation pattern characterized by the core
      triad of retrognathia, glossoptosis, and cleft palate that causes difficulty in
      glossopharyngeal-laryngeal-vagal functions. The etiology of PRS remains largely
      unknown; previous reports have suggested that it is caused by intrauterine
      constriction or external conditions such as oligohydramnios, breech position, or
      abnormal uterine anatomy. Genetic causes include occurrence as a manifestation of
      many single gene conditions and chromosomal rearrangements. Positional effect on
      some loci or genes, including SOX9 has also been posited as a cause. Here, we
      report on an 18-month-old girl born with isolated PRS. Clinical chromosome
      microarray analysis (CMA) revealed a maternally inherited ~623 kb microdeletion
      that is -725 kb upstream of 5' SOX9 at chromosome locus 17q24.3. Her mother had
      cleft palate. This region, although devoid of any genes, is known to have a
      position effect on SOX9 due to elimination of highly conserved non-coding cis
      regulatory elements. This report supports the evidence that deregulation of an
      intact SOX9 coding region is a cause of or associated with isolated PRS, and
      provides further evidence that CMA in the clinical setting is a powerful tool in
      detecting microdeletions in gene "desert" regions that have pathogenic position
      effect on specific genes.

PMID- 23532966
TI  - Quantum influences in the diffusive motion of pyrrole on Cu(111).

PMID- 23532967
TI  - Enhanced supercapacitor performance of N-doped mesoporous carbons prepared from a
      gelatin biomolecule.

PMID- 23532968
TI  - Unraveling the evolutionary history of the nematode Pristionchus pacificus: from
      lineage diversification to island colonization.
AB  - The hermaphroditic nematode Pristionchus pacificus is a model organism with a
      range of fully developed genetic tools. The species is globally widespread and
      highly diverse genetically, consisting of four major independent lineages
      (lineages A, B, C, and D). Despite its young age (~2.1 Ma), volcanic La Reunion
      Island harbors all four lineages. Ecological and population genetic research
      studies suggest that this diversity is due to repeated independent island
      colonizations by P. pacificus. Here, we use model-based statistical methods to
      rigorously test hypotheses regarding the evolutionary history of P. pacificus.
      First, we employ divergence analyses to date diversification events among the
      four "world" lineages. Next, we examine demographic properties of a subset of
      four populations ("a", "b", "c", and "d"), present on La Reunion Island. Finally,
      we use the results of the divergence and demographic analyses to inform a
      modeling-based approximate Bayesian computation (ABC) approach, where we test
      hypotheses about the order and timing of establishment of the Reunion
      populations. Our dating estimates place the recent common ancestor of P.
      pacificus lineages at nearly 500,000 generations past. Our demographic analysis
      supports recent (<150,000 generations) spatial expansion for the island
      populations, and our ABC approach supports c>a>b>d as the most likely
      colonization order of the island populations. Collectively, our study
      comprehensively improves previous inferences about the evolutionary history of P.
      pacificus.

PMID- 23532970
TI  - Adenosine kinase is a key determinant for the anti-HCV activity of ribavirin.
AB  - Ribavirin (RBV) is often used in conjunction with interferon-based therapy for
      patients with chronic hepatitis C. There is a drastic difference in the anti
      hepatitis C virus (HCV) activity of RBV between the HuH-7-derived assay system,
      OR6, possessing the RBV-resistant phenotype (50% effective concentration [EC50 ]:
      >100 uM) and the recently discovered Li23-derived assay system, ORL8, possessing
      the RBV-sensitive phenotype (EC50 : 8 uM; clinically achievable concentration).
      This is because the anti-HCV activity of RBV was mediated by the inhibition of
      inosine monophosphate dehydrogenase in RBV-sensitive ORL8 cells harboring HCV
      RNA. By means of comparative analyses using RBV-resistant OR6 cells and RBV
      sensitive ORL8 cells, we tried to identify host factor(s) determining the anti
      HCV activity of RBV. We found that the expression of adenosine kinase (ADK) in
      ORL8 cells was significantly higher than that in RBV-resistant OR6 cells
      harboring HCV RNA. Ectopic ADK expression in OR6 cells converted them from an RBV
      resistant to an RBV-sensitive phenotype, and inhibition of ADK abolished the
      activity of RBV. We showed that the differential ADK expression between ORL8 and
      OR6 cells was not the result of genetic polymorphisms in the ADK gene promoter
      region and was not mediated by a microRNA control mechanism. We found that the 5'
      untranslated region (UTR) of ADK messenger RNA in ORL8 cells was longer than that
      in OR6 cells, and that only a long 5' UTR possessed internal ribosome entry site
      (IRES) activity. Finally, we demonstrated that the long 5' UTR functioned as an
      IRES in primary human hepatocytes. CONCLUSION: These results indicate that ADK
      acts as a determinant for the activity of RBV and provide new insight into the
      molecular mechanism underlying differential drug sensitivity.

PMID- 23532971
TI  - Hydrogen production by dehydrogenation of formic acid on atomically dispersed
      gold on ceria.
AB  - Less is More: Atomically dispersed gold species catalyze the decomposition of
      formic acid through the dehydrogenation pathway at near-ambient temperatures.
      Gold on ceria is demonstrated to be an effective and stable catalyst. By using
      this catalyst, mechanistic insights are obtained that can lead to the use of
      trace amounts of gold to achieve robust and cost-effective catalysts.

PMID- 23532969
TI  - Gene therapy with AAV2-CDNF provides functional benefits in a rat model of
      Parkinson's disease.
AB  - Cerebral dopamine neurotrophic factor (CDNF) protein has been shown to protect
      the nigrostriatal dopaminergic pathway when given as intrastriatal infusions in
      rat and mouse models of Parkinson's disease (PD). In this study, we assessed the
      neuroprotective effect of CDNF delivered with a recombinant adeno-associated
      viral (AAV) serotype 2 vector in a rat 6-hydroxydopamine (6-OHDA) model of PD.
      AAV2 vectors encoding CDNF, glial cell line-derived neurotrophic factor (GDNF),
      or green fluorescent protein were injected into the rat striatum. Protein
      expression analysis showed that our AAV2 vector efficiently delivered the
      neurotrophic factor genes into the brain and gave rise to a long-lasting
      expression of the proteins. Two weeks after AAV2 vector injection, 6-OHDA was
      injected into the rat striatum, creating a progressive degeneration of the
      nigrostriatal dopaminergic system. Treatment with AAV2-CDNF resulted in a marked
      decrease in amphetamine-induced ipsilateral rotations while it provided only
      partial protection of tyrosine hydroxylase (TH)-immunoreactive cells in the rat
      substantia nigra pars compacta and TH-reactive fibers in the striatum. Results
      from this study provide additional evidence that CDNF can be considered a
      potential treatment of Parkinson's disease.

PMID- 23532972
TI  - Flexor hallucis brevis spasm.

PMID- 23532973
TI  - Mosaic deletion of the NF1 gene in a patient with cognitive disability and
      dysmorphic features but without diagnostic features of NF1.

PMID- 23532974
TI  - Cultivating our "frienemies": viewing immunity as microbiome management.
AB  - Immunology has been studied and understood in the context of the compelling
      problems of infectious disease. But our rapidly growing knowledge of immune
      interactions with our healthy microbiota, and the many benefits it confers,
      suggests there may be value to an alternative view: that mechanisms of defense
      against pathogens are one aspect of a complex system with the broader purpose of
      managing our healthy microbiome. From this perspective, adaptive immunity may be
      viewed as a flexible system for simultaneously recruiting and managing a near
      limitless number of potential symbionts. This perspective can allow for
      reinterpretation of many observations and can suggest new experiments to help us
      better understand our complex interactions with the microbes that surround us.

PMID- 23532975
TI  - Overexpression of specific cysteine peptidases confers pathogenicity to a
      nonpathogenic Entamoeba histolytica clone.
AB  - Cysteine peptidases (CPs) of Entamoeba histolytica are considered to be important
      pathogenicity factors. Previous studies have found that under standard axenic
      culture conditions, only four (ehcp-a1, ehcp-a2, ehcp-a5, and ehcp-a7) out of 35
      papain-like ehcp genes present in the E. histolytica genome are expressed at high
      levels. Little is known about the expression of CPs in E. histolytica during
      amoebic liver abscess (ALA) formation. In the current study, a quantitative real
      time PCR assay was developed to determine the expression of the various ehcp
      genes during ALA formation in animal models. Increased expression of four ehcp
      genes (ehcp-a3, -a4, -a10, and -c13) was detected in the gerbil and mouse models.
      Increased expression of another three ehcp genes (ehcp-a5, -a6, and -a7) was
      detected in the mouse model only, and two other ehcp genes (ehcp-b8 and -b9)
      showed increased expression in the gerbil model only. Trophozoites of the
      nonpathogenic E. histolytica HM-1:IMSS clone A1, which was unable to induce ALAs,
      were transfected with vectors enabling overexpression of those CPs that are
      expressed at high levels under culture conditions or during ALA formation.
      Interestingly, overexpression of ehcp-b8, -b9, and -c13 restored the pathogenic
      phenotype of the nonpathogenic clone A1 whereas overexpression of various other
      peptidase genes had no effect on the pathogenicity of this clone.

PMID- 23532977
TI  - Are men more likely than women to commit scientific misconduct? Maybe, maybe not.
AB  - In their study published in January 2013 in mBio, Fang et al. reviewed records
      from the Office of Research Integrity (ORI) and found more cases of scientific
      misconduct committed by men than women, particularly by faculty (F. C. Fang, J.
      W. Bennett, and A. Casadevall, mBio 4:1-3, 2013). Powerful social norms shape the
      way men and women behave, and implicit gender schemas can lead to different
      evaluation standards for men and women for tasks stereotypically linked to one
      gender. It is possible that norms for acceptable male and female behavior could
      lead to a lower threshold for men than women to engage in the risky behavior of
      scientific misconduct. It is also possible that women and men commit scientific
      fraud at the same rate but that, because crime is a male-gendered domain,
      evaluators require more proof of the criminal "competence" of women for an
      investigation to rise to the level of an ORI case or that female gender norms for
      likeability and a lower apology threshold more often prevent escalation of
      women's fraud beyond a local level. Male scientists also have more opportunity to
      commit fraud than female scientists because they receive more NIH research
      funding--a finding that may also be influenced by gender schemas. We cannot
      conclude from the ORI data that men are more likely than women to risk the
      consequences of committing scientific misconduct simply because risk taking
      aligns with male gender stereotypes. Neither can we conclude that because men are
      more likely than women to commit fraud in other contexts, men are also more
      likely than women to commit scientific fraud. We can conclude, however, that
      scientific misconduct, regardless of who commits it, diminishes all who
      contribute to the scientific enterprise.

PMID- 23532976
TI  - The fungal pathogen Aspergillus fumigatus regulates growth, metabolism, and
      stress resistance in response to light.
AB  - Light is a pervasive environmental factor that regulates development, stress
      resistance, and even virulence in numerous fungal species. Though much research
      has focused on signaling pathways in Aspergillus fumigatus, an understanding of
      how this pathogen responds to light is lacking. In this report, we demonstrate
      that the fungus does indeed respond to both blue and red portions of the visible
      spectrum. Included in the A. fumigatus light response is a reduction in conidial
      germination rates, increased hyphal pigmentation, enhanced resistance to acute
      ultraviolet and oxidative stresses, and an increased susceptibility to cell wall
      perturbation. By performing gene deletion analyses, we have found that the
      predicted blue light receptor LreA and red light receptor FphA play unique and
      overlapping roles in regulating the described photoresponsive behaviors of A.
      fumigatus. However, our data also indicate that the photobiology of this fungus
      is complex and likely involves input from additional photosensory pathways beyond
      those analyzed here. Finally, whole-genome microarray analysis has revealed that
      A. fumigatus broadly regulates a variety of metabolic genes in response to light,
      including those involved in respiration, amino acid metabolism, and metal
      homeostasis. Together, these data demonstrate the importance of the photic
      environment on the physiology of A. fumigatus and provide a basis for future
      studies into this unexplored area of its biology.

PMID- 23532978
TI  - Comparative analysis of Chlamydia psittaci genomes reveals the recent emergence
      of a pathogenic lineage with a broad host range.
AB  - Chlamydia psittaci is an obligate intracellular bacterium. Interest in Chlamydia
      stems from its high degree of virulence as an intestinal and pulmonary pathogen
      across a broad range of animals, including humans. C. psittaci human pulmonary
      infections, referred to as psittacosis, can be life-threatening, which is why the
      organism was developed as a bioweapon in the 20th century and is listed as a CDC
      biothreat agent. One remarkable recent result from comparative genomics is the
      finding of frequent homologous recombination across the genome of the sexually
      transmitted and trachoma pathogen Chlamydia trachomatis. We sought to determine
      if similar evolutionary dynamics occurred in C. psittaci. We analyzed 20 C.
      psittaci genomes from diverse strains representing the nine known serotypes of
      the organism as well as infections in a range of birds and mammals, including
      humans. Genome annotation revealed a core genome in all strains of 911 genes. Our
      analyses showed that C. psittaci has a history of frequently switching hosts and
      undergoing recombination more often than C. trachomatis. Evolutionary history
      reconstructions showed genome-wide homologous recombination and evidence of whole
      plasmid exchange. Tracking the origins of recombinant segments revealed that some
      strains have imported DNA from as-yet-unsampled or -unsequenced C. psittaci
      lineages or other Chlamydiaceae species. Three ancestral populations of C.
      psittaci were predicted, explaining the current population structure. Molecular
      clock analysis found that certain strains are part of a clonal epidemic expansion
      likely introduced into North America by South American bird traders, suggesting
      that psittacosis is a recently emerged disease originating in New World parrots.

PMID- 23532979
TI  - Inhibition of viral pathogenesis and promotion of the septic shock response to
      bacterial infection by IRF-3 are regulated by the acetylation and phosphorylation
      of its coactivators.
AB  - Interferon (IFN) is required for protecting mice from viral pathogenesis;
      reciprocally, it mediates the deleterious septic shock response to bacterial
      infection. The critical transcription factor for IFN induction, in both cases, is
      IRF-3, which is activated by TLR3 or RIG-I signaling in response to virus
      infection and TLR4 signaling in response to bacterial infection. Here, we report
      that IRF-3's transcriptional activity required its coactivators, beta-catenin and
      CBP, to be modified by HDAC6-mediated deacetylation and protein kinase C isozyme
      beta (PKC-beta)-mediated phosphorylation, respectively, so that activated nuclear
      IRF-3 could form a stable transcription initiation complex at the target gene
      promoters. beta-Catenin bridges IRF-3 and CBP, and the modifications were
      required specifically for the interaction between beta-catenin and CBP but not
      beta-catenin and IRF-3. Consequently, like IRF-3(-/-) mice, HDAC6(-/-) mice were
      resistant to bacterial lipopolysaccharide-induced septic shock. Conversely, they
      were highly susceptible to pathogenesis caused by Sendai virus infection. Thus,
      HDAC6 is an essential component of the innate immune response to microbial
      infection.

PMID- 23532980
TI  - Skin and mucosa care in systemic sclerosis--patients' and family caregivers'
      experiences and expectations of a specific education programme: a qualitative
      study.
AB  - BACKGROUND: Skin and mucosal manifestations such as skin thickening, pruritus,
      reduced microvascular circulation, digital lesions, appearance-related changes,
      and dryness of the eyes and mucosa are common in systemic sclerosis (SSc). A
      specific skin and mucosa care education programme for patients and their family
      caregivers should increase their self-efficacy and improve coping strategies.
      AIMS: The aims of this qualitative study were to explore the participants'
      experiences of both everyday life with skin and mucosal manifestations and the
      programme itself, while identifying unmet needs for programme development.
      METHODS: Narrative interviews were conducted with eight SSc patients and two
      family caregivers of individuals with SSc. Using qualitative content analysis
      techniques, the transcribed interviews were systematically summarized and
      categories inductively developed. RESULTS: The findings illustrated participants'
      experiences of skin and mucosal symptoms and revealed them to be experts in
      finding the right therapy mix alone (before diagnosis) and also in collaboration
      with health professionals (after diagnosis). Participants emphasized that the
      programme gave them useful education on skin and mucosa care. They described how
      they had to cope alone with the lack of information on pathophysiology, people's
      reactions, and the impact on their family and working lives. Nevertheless,
      participants said that they maintained a positive attitude by not dwelling on
      future disabilities. CONCLUSIONS: Patients and family caregivers benefited from
      the individualized and SSc-specific education on skin and mucosa care. Future
      improvements to the programme should focus on imparting understandable
      information on SSc pathophysiology, dealing with disfigurement and seeking
      reliable disease information, as well as facilitating peer support.

PMID- 23532981
TI  - Health care access and health care workforce for immigrant workers in the
      agriculture, forestry, and fisheries sector in the southeastern US.
AB  - BACKGROUND: The Agriculture, Forestry, and Fishery (AgFF) Sector workforce in the
      US is comprised primarily of Latino immigrants. Health care access for these
      workers is limited and increases health disparities. METHODS: This article
      addresses health care access for immigrant workers in the AgFF Sector, and the
      workforce providing care to these workers. CONTENTS: Immigrant workers bear a
      disproportionate burden of poverty and ill health and additionally face
      significant occupational hazards. AgFF laborers largely are uninsured, ineligible
      for benefits, and unable to afford health services. The new Affordable Care Act
      will likely not benefit such individuals. Community and Migrant Health Centers
      (C/MHCs) are the frontline of health care access for immigrant AgFF workers.
      C/MHCs offer discounted health services that are tailored to meet the special
      needs of their underserved clientele. C/MHCs struggle, however, with a shortage
      of primary care providers and staff prepared to treat occupational illness and
      injury among AgFF workers. A number of programs across the US aim to increase the
      number of primary care physicians and care givers trained in occupational health
      at C/MHCs. While such programs are beneficial, substantial action is needed at
      the national level to strengthen and expand the C/MHC system and to establish
      widely Medical Home models and Accountable Care Organizations. System-wide policy
      changes alone have the potential to reduce and eliminate the rampant health
      disparities experienced by the immigrant workers who sustain the vital
      Agricultural, Forestry, and Fishery sector in the US.

PMID- 23532982
TI  - The pesticide dichlorvos disrupts mitotic division by delocalizing the kinesin
      Kif2a from centrosomes.
AB  - The molecular mechanism(s) mediating long-term adverse effects of dichlorvos, a
      widely used insecticide, are still unclear. Our work uncovered a new cellular
      effect of dichlorvos in cultured human cells, i.e. its capacity to induce
      extremely aberrant mitotic spindles with monopolar microtubule arrays that were
      associated with hypercondensed chromosomes and pyknotic chromatin masses.
      Monopolar spindles produced by dichlorvos treatment were characterized by the
      delocalization of the depolymerizing kinesin Kif2a from spindle poles. Dichlorvos
      induced spindle monopolarity could be reversed by promoting microtubule
      stabilization through chemical treatment or by inhibiting the depolymerizing
      function of the kinesin MCAK at kinetochores. These findings demonstrate that
      dichlorvos inhibits the depolymerizing activity of Kif2a at centrosomes and
      thereby disrupts the balance of opposing centrosomal and kinetochore forces
      controlling spindle bipolarity during prometaphase. Dichlorvos-induced defects in
      spindle bipolarity may be responsible for the previously reported induction of
      aneuploidy by this chemical. Collectively, these results indicate that
      environmental chemicals, such as dichlorvos, may promote chromosome instability
      by interfering with the cell division machinery.

PMID- 23532983
TI  - Atrazine degradation in soil: effects of adjuvants and a comparison of three
      mathematical models.
AB  - BACKGROUND: There are few reports on the effects of spray adjuvants on pesticide
      persistence. The role of three adjuvants used with atrazine on the herbicide's
      degradation in soil was examined. Three mathematical models were used to describe
      pesticide disappearance from soil: pseudo-first-order kinetics, the non-linear
      Gustafson-Holden model and the biexponential function. RESULTS: A mixture of
      atrazine with Atpolan 80 EC significantly inhibited herbicide soil degradation
      (DT50  = 78 days), while Adpros 85 SL and Break-Thru S 240 (DT50  = 25 and 24
      days respectively) had little effect (DT50  = 22 days, atrazine alone). These
      results suggest that adjuvant can be a factor in field persistence. DT50 values
      obtained using the Gustafson-Holden and biexponential models were similar. Only
      the biexponential model requires an iterative method. CONCLUSION: A significant
      effect of one adjuvant on atrazine persistence in soil was observed. The
      biexponential model best described the disappearance of atrazine in the soil, as
      indicated by the values of R(2) and RMS and the relative concentration of the
      herbicide in the soil.

PMID- 23532984
TI  - The flavoprotein dodecin as a redox probe for electron transfer through DNA.

PMID- 23532985
TI  - Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic
      analysis of plasma and cerebrospinal fluid drug concentrations in Japanese
      patients with non-small cell lung cancer.
AB  - BACKGROUND: Erlotinib shows large inter-patient pharmacokinetic variability, but
      the impact of early drug exposure and genetic variations on the clinical outcomes
      of erlotinib remains fully investigated. The primary objective of this study was
      to clarify the population pharmacokinetics/pharmacodynamics of erlotinib in
      Japanese patients with non-small cell lung cancer (NSCLC). The secondary
      objective was to identify genetic determinant(s) for the cerebrospinal fluid
      (CSF) permeability of erlotinib and its active metabolite OSI-420. METHODS: A
      total of 88 patients treated with erlotinib (150 mg/day) were enrolled, and CSF
      samples were available from 23 of these patients with leptomeningeal metastases.
      Plasma and CSF concentrations of erlotinib and OSI-420 were measured by high
      performance liquid chromatography with UV detection. Population pharmacokinetic
      analysis was performed with the nonlinear mixed-effects modelling program NONMEM.
      Germline mutations including ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A),
      and CYP3A5 (6986A>G) polymorphisms, as well as somatic EGFR activating mutations
      if available, were examined. Early exposure to erlotinib and its safety/efficacy
      relationship were evaluated. RESULTS: The apparent clearance of erlotinib and OSI
      420 were significantly decreased by 24 and 35 % in patients with the ABCG2 421A
      allele, respectively (p < 0.001), while ABCB1 and CYP3A5 polymorphisms did not
      affect their apparent clearance. The ABCG2 421A allele was significantly
      associated with increased CSF penetration for both erlotinib and OSI-420 (p <
      0.05). Furthermore, the incidence of grade >=2 diarrhea was significantly higher
      in patients harboring this mutant allele (p = 0.035). A multivariate logistic
      regression model showed that erlotinib trough (C0) levels on day 8 were an
      independent risk factor for the development of grade >=2 diarrhea (p = 0.037) and
      skin rash (p = 0.031). Interstitial lung disease (ILD)-like events occurred in 3
      patients (3.4 %), and the median value of erlotinib C0 levels adjacent to these
      events was approximately 3 times higher than that in patients who did not develop
      ILD (3253 versus 1107 ng/mL; p = 0.014). The objective response rate in the EGFR
      wild-type group was marginally higher in patients achieving higher erlotinib C0
      levels (>=1711 ng/mL) than that in patients having lower erlotinib C0 levels (38
      versus 5 %; p = 0.058), whereas no greater response was observed in the higher
      group (67 %) versus the lower group (77 %) within EGFR mutation-positive patients
      (p = 0.62). CONCLUSIONS: ABCG2 can influence the apparent clearance of erlotinib
      and OSI-420, and their CSF permeabilities in patients with NSCLC. Our preliminary
      findings indicate that early exposure to erlotinib may be associated with the
      development of adverse events and that increased erlotinib exposure may be
      relevant to the antitumor effects in EGFR wild-type patients while having less of
      an impact on the tumor response in EGFR mutation-positive patients.

PMID- 23532987
TI  - Peripheral neuropathy: assessment of proximal nerve integrity by diffusion tensor
      imaging.
AB  - INTRODUCTION: We investigated the utility of diffusion tensor imaging (DTI) for
      detecting neuropathic changes in proximal nerve segments in patients with
      peripheral neuropathy. METHODS: Twenty-one individuals with (n = 11) and without
      (n = 10) peripheral neuropathy underwent DTI of a defined sciatic nerve segment.
      Patients and controls were evaluated by clinical examination and nerve conduction
      studies at baseline and 6 months after the initial DTI scan. RESULTS: The mean
      fractional anisotropy (FA) value was significantly lower in sciatic nerves from
      patients with peripheral neuropathy as compared with controls. Sciatic nerve FA
      values correlated with clinical disability scores and electrophysiological
      parameters of axonal damage at baseline and 6 months after MRI scan. CONCLUSIONS:
      DTI-derived FA values are a sensitive measure to discriminate healthy from
      functionally impaired human sciatic nerve segments. DTI of proximal nerve
      segments may be useful for estimating the proximal axonal degeneration burden in
      patients with peripheral neuropathies.

PMID- 23532986
TI  - Peripheral CD4(+) T-cell tolerance is induced in vivo by rare antigen-bearing B
      cells in follicular, marginal zone, and B-1 subsets.
AB  - B cells are efficient APCs when they internalize antigen via BCR-mediated uptake.
      Adoptively transferred antigen-presenting B cells can induce T-cell tolerance to
      foreign and self antigens; however, it is unknown whether endogenous B cells
      presenting self-peptides interact with naive T cells and contribute to peripheral
      T-cell self-tolerance. Moreover, the relative abilities of mature B-cell subsets
      to induce T-cell tolerance have not been examined. To address these questions, we
      created a new mouse model wherein a very small fraction of B cells expresses an
      antigen transgene that cannot be transferred to other APCs. We limited antigen
      expression to follicular, marginal zone, or B-1 B-cell subsets and found that
      small numbers of each subset interacted with naive antigen-specific T cells.
      Although antigen expressed by B-1 B cells induced the most T-cell division,
      divided T cells subsequently disappeared from secondary lymphoid tissues.
      Independent of which B-cell subset presented antigen, the remaining T cells were
      rendered hypo-responsive, and this effect was not associated with Foxp3
      expression. Our data show that physiologically relevant proportions of B cells
      can mediate peripheral T-cell tolerance, and suggest that the mechanisms of
      tolerance induction might differ among follicular, marginal zone, and B-1 B-cell
      subsets. 

PMID- 23532988
TI  - Preferring thin people does not imply derogating fat people. A Rasch analysis of
      the implicit weight attitude.
AB  - OBJECTIVE: The meaning of the implicit weight attitude in individuals of
      different weight by distinguishing the contribution of positive and negative
      associations to the overall measure was investigated. DESIGN AND METHODS: The
      implicit weight attitude was assessed using the Implicit Association Test. A
      Rasch model was used to identify which stimuli most affected the implicit
      measure. Explicit attitudes were assessed with a thin-fat preference scale, and
      thermometer scales for both thin and fat people. The sample consists of 510
      individuals categorized according to their BMI. RESULTS AND CONCLUSION: A
      significant implicit preference for thin relative to fat people was observed in
      all weight groups. In normal weight and obese individuals, the preference was
      mostly affected by positive stimuli (more easily associated with thin than with
      fat people). In underweight individuals, the preference was mostly guided by
      positive (more easily associated with thin than with fat people) and negative
      (more easily associated with fat than with thin people) stimuli. In overweight
      individuals, all stimuli contributed to the preference in a similar way. In all
      weight groups, the implicit weight attitude correlated with the explicit
      preference and/or the thin thermometer, whereas it never correlated with the fat
      thermometer. A pro-thin bias was observed in normal weight and obese individuals,
      whereas both a pro-thin and an anti-fat bias were observed in underweight
      individuals. A clear preference for thin people relative to fat people was
      observed in overweight individuals. Therefore, uncritically interpreting the
      implicit preference for thin people as a sign of derogating fat people might be
      misleading.

PMID- 23532989
TI  - The relationship between anthropometric indexes of adiposity and vascular
      function in the FATE cohort.
AB  - OBJECTIVE: Numerous indexes of adiposity have been proposed and are currently in
      use in clinical practice and research. However, the correlation of these indexes
      with measures of vascular health remain poorly defined. This study investigated
      which measure of adiposity is most strongly associated with endothelial function.
      DESIGN AND METHODS: Data from the Firefighters And Their Endothelium (FATE) study
      was used. The relationships between three measures of vascular function: flow
      mediated dilation (FMD), hyperemic velocity time integral (VTI), and hyperemic
      shear stress (HSS), and five measures of adiposity: BMI, waist circumference
      (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body adiposity
      index (BAI) were tested. Univariate comparisons were made, and subsequently
      models adjusted for traditional risk factors were constructed. RESULTS: A total
      of 1,462 male firefighters (mean age 49 +/- 9) without cardiovascular disease
      comprised the study population. No measure of adiposity correlated with FMD; all
      five measures of adiposity were negatively correlated with VTI and HSS (P values
      <0.0001), with WHtR most strongly correlated with VTI, and WC most strongly
      correlated with HSS (both P < 0.05). In models including all five measures of
      obesity simultaneously, BMI, WC, and WHtR were all predictive of HSS (all P
      values <0.05), and BMI and WHR were both predictive of VTI (P values <0.05).
      CONCLUSIONS: Anthropometric measures of adiposity may help refine estimations of
      atherosclerotic burden. BMI was most consistently associated with endothelial
      dysfunction, but measures of adiposity that reflect distribution of mass were
      additive.

PMID- 23532990
TI  - Family-based hip-hop to health: outcome results.
AB  - OBJECTIVE: This pilot study tested the feasibility of Family-Based Hip-Hop to
      Health, a school-based obesity prevention intervention for 3-5-year-old Latino
      children and their parents, and estimated its effectiveness in producing smaller
      average changes in BMI at 1-year follow-up. DESIGN AND METHODS: Four Head Start
      preschools administered through the Chicago Public Schools were randomly assigned
      to receive a Family-Based Intervention (FBI) or a General Health Intervention
      (GHI). RESULTS: Parents signed consent forms for 147 of the 157 children
      enrolled. Both the school-based and family-based components of the intervention
      were feasible, but attendance for the parent intervention sessions was low.
      Contrary to expectations, a downtrend in BMI Z-score was observed in both the
      intervention and control groups. CONCLUSIONS: While the data reflect a downward
      trend in obesity among these young Hispanic children, obesity rates remained
      higher at 1-year follow-up (15%) than those reported by the National Health and
      Nutrition Examination Survey (2009-2010) for 2-5-year-old children (12.1%).
      Developing evidence-based strategies for obesity prevention among Hispanic
      families remains a challenge.

PMID- 23532991
TI  - Weight loss can lead to resolution of gastroesophageal reflux disease symptoms: a
      prospective intervention trial.
AB  - OBJECTIVE: Weight gain is an important risk factor for gastroesophageal reflux
      disease (GERD); however, whether weight loss can lead to resolution of GERD
      symptoms is not clear. Our aim was to measure the impact of weight loss on GERD
      symptoms. DESIGN AND METHODS: In a prospective cohort study at a tertiary
      referral center, overweight/obese subjects (BMI 25-39.9 kg/m2) were enrolled in a
      structured weight loss program. Weight loss strategies included dietary
      modifications, increased physical activity and behavioral changes. At baseline
      and at 6 months, BMI and waist circumference were measured and all participants
      completed a validated reflux disease questionnaire. RESULTS: A total of 332 adult
      subjects, mean age 46 years and 66% women were prospectively enrolled. At
      baseline, the mean body weight, BMI, and waist circumference were 101 (+/-18) kg,
      35 (+/-5) kg/m2 and 103 (+/-13) cm. At 6 months, majority of the subjects (97%)
      lost weight (average weight loss: 13 +/- 7.7 kg) and as compared with baseline,
      there was a significant decrease in the overall prevalence of GERD (15 vs. 37%; P
      < 0.01) and the mean GERD symptom score (1.8 vs. 5.5; P < 0.01). Overall, 81% of
      the subjects had reduction in GERD symptom scores; 65% had complete resolution
      and 15% had partial resolution of reflux symptoms. There was a significant
      correlation between % body weight loss and reduction in GERD symptom scores (r =
      0.17, P < 0.05). CONCLUSIONS: In conclusion, the overall prevalence of GERD
      symptoms is high (37%) in overweight and obese subjects. A structured weight loss
      program can lead to complete resolution of GERD symptoms in the majority of these
      subjects.

PMID- 23532992
TI  - Serum hemorphin-7 levels are decreased in obesity.
AB  - OBJECTIVE: Hemorphin peptides exhibit biological activities that interfere with
      the endorphin system, the inflammatory response, and blood-pressure control. VV
      hemorphin-7 and LVV-hemorphin-7 peptides exert a hypotensive effect, in
      particular, by inhibiting the renin-angiotensin system. Furthermore, levels of
      circulating hemorphin-7 peptides have been found to be decreased in diseases such
      as type 1 and type 2 diabetes. DESIGN AND METHODS: Because type 2 diabetes and
      obesity share common features, such as insulin resistance, microinflammation,
      high glomerular-filtration rate (GFR), and cardiovascular risk, we evaluated
      serum VV-hemorphin-7 like immunoreactivity (VVH7-i.r.) levels, using an enzyme
      linked immunosorbent assay method, on a group of 54 obese subjects without
      diabetes or hypertension, compared with a group of 33 healthy normal-weight
      subjects. RESULTS: Circulating VVH7-i.r. levels were significantly decreased in
      the obese group compared with the control group (1.98 +/- 0.19 vs. 4.86 +/- 0.54
      umol/l, respectively, P < 0.01), and a significant negative correlation between
      VVH7-i.r. and diastolic blood pressure (DBP) was found in obese patients (r = 
      0.35, P = 0.011). There was no significant correlation between VVH7-i.r. level
      and insulin resistance, metabolic syndrome, or GFR. CONCLUSIONS: The decreased
      serum hemorphin-7 found in obese subjects, as in diabetes, may contribute to the
      development of hypertension and to the cardiovascular risk associated with these
      metabolic diseases.

PMID- 23532993
TI  - Adherence to behavioral targets and treatment attendance during a pediatric
      weight control trial.
AB  - OBJECTIVE: Better weight loss outcomes are achieved in adults and youth who
      adhere to obesity treatment regimens (i.e., session attendance and prescribed
      changes in weight control behaviors). However, more research is needed regarding
      children's adherence to a range of behaviors relevant for weight maintenance over
      long-term follow-up. DESIGN AND METHODS: Overweight children (N = 101, aged 7-12
      years), along with an overweight parent, participated in a 20-week family-based
      behavioral weight loss treatment (FBT) and were then assigned to either a
      behaviorally focused or socially focused 16-week weight maintenance treatment
      (MT). Treatment attendance and child and parent adherence (i.e., reported use of
      skills targeted within treatment) were examined in relation to child percent
      overweight change from baseline to post-FBT, post-MT, and 2-year follow-up.
      RESULTS: Higher attendance predicted better child weight outcomes at post-MT, but
      not at 2-year follow-up. Adherence to self-regulatory skills/goal-setting skills
      predicted child weight outcomes at 2-year follow-up among the behaviorally
      focused MT group. CONCLUSIONS: Future research is needed to examine mediators of
      change within family-based weight control interventions, including behavioral and
      socially based targets. Incorporating self-regulatory weight maintenance skills
      into a comprehensive MT may maximize children's sustained weight control.

PMID- 23532995
TI  - miR-148a plays a pivotal role in the liver by promoting the hepatospecific
      phenotype and suppressing the invasiveness of transformed cells.
AB  - MicroRNAs (miRNAs) are evolutionary conserved small RNAs that post
      transcriptionally regulate the expression of target genes. To date, the role of
      miRNAs in liver development is not fully understood. By using an experimental
      model that allows the induced and controlled differentiation of mouse fetal
      hepatoblasts (MFHs) into mature hepatocytes, we identified miR-148a as a
      hepatospecific miRNA highly expressed in adult liver. The main finding of this
      study revealed that miR-148a was critical for hepatic differentiation through the
      direct targeting of DNA methyltransferase (DNMT) 1, a major enzyme responsible
      for epigenetic silencing, thereby allowing the promotion of the "adult liver"
      phenotype. It was also confirmed that the reduction of DNMT1 by RNA interference
      significantly promoted the expression of the major hepatic biomarkers. In
      addition to the essential role of miR-148a in hepatocyte maturation, we
      identified its beneficial effect through the repression of hepatocellular
      carcinoma (HCC) cell malignancy. miR-148a expression was frequently down
      regulated in biopsies of HCC patients as well as in mouse and human HCC cell
      lines. Overexpressing miR-148a led to an enhancement of albumin production and a
      drastic inhibition of the invasive properties of HCC cells, whereas miR-148a
      silencing had the opposite consequences. Finally, we showed that miR-148a exerted
      its tumor-suppressive effect by regulating the c-Met oncogene, regardless of the
      DNMT1 expression level. CONCLUSION: miR-148a is essential for the physiology of
      the liver because it promotes the hepatospecific phenotype and acts as a tumor
      suppressor. Most important, this report is the first to demonstrate a functional
      role for a specific miRNA in liver development through regulation of the DNMT1
      enzyme.

PMID- 23532994
TI  - Circulating levels of persistent organic pollutants in relation to visceral and
      subcutaneous adipose tissue by abdominal MRI.
AB  - OBJECTIVE: We and others have shown relationships between circulating levels of
      persistent organic pollutants (POPs) and different measures of obesity in both
      cross-sectional and prospective studies. Since viscerally located fat seems to be
      the most harmful type, we investigated whether plasma POP levels were more
      closely related to visceral adipose tissue (VAT) than to subcutaneous adipose
      tissue (SAT). DESIGN AND METHODS: Thousand hundred and sixteen subjects aged 70
      years were investigated in the Prospective Investigation of the Vasculature in
      Uppsala Seniors (PIVUS) study; 23 POPs were analyzed using high-resolution gas
      chromatography/high-resolution mass spectrometry. Abdominal magnetic resonance
      imaging, measuring VAT and SAT, respectively, was performed in a representative
      subsample of 287 subjects. RESULTS: The less chlorinated polychlorinated biphenyl
      (PCB) congeners (105 and 118), and the pesticides
      dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and trans
      nonachlordane (TNC) were positively related to both VAT and SAT, whereas the more
      highly chlorinated PCBs (153, 156, 157, 169, 170, 180, 194, 206, and 209) were
      inversely related to both VAT and SAT. PCB189 was related to the VAT/SAT ratio in
      an inverted U-shaped manner (P = 0.0008). CONCLUSIONS: In conclusion, the results
      were in accordance with our previous studies using waist circumference and fat
      mass as obesity measure. However, the novel finding that PCB189 was related to
      the VAT/SAT ratio deserves further investigation since exposure to this PCB
      congener, which has previously been linked to diabetes development, might thereby
      play a role in the distribution of abdominal adipose tissue.

PMID- 23532996
TI  - Development and validation of a method for the analysis of paroxetine HCl by
      circular dichroism.
AB  - A simple, rapid, and sensitive method for the analysis of paroxetine, in tablets
      as well as the pure drug, by circular dichroism is described. The method was
      validated for repeatability, linearity, limit of detection, limit of
      quantification, and recovery according to the International Conference on
      Harmonization guidelines. Excellent results were obtained, within the globally
      accepted validation reference values, particularly taking into account the low
      concentration levels investigated. This is the first report of the quantitation
      of paroxetine, a chiral drug, without previous separation of the analyte.
      Additionally, the solid state CD spectrum of PXT was obtained.

PMID- 23532997
TI  - (+)-9-Benzyloxy-alpha-dihydrotetrabenazine as an important intermediate for the
      VMAT2 imaging agents: absolute configuration and chiral recognition.
AB  - This article reports, for the first time, on the absolute configuration of (+)-9
      benzyloxy-alpha-dihydrotetrabenazine (8), as determined from the perspective of X
      ray crystallography. Compound 8 was prepared by a six-step reaction using 3
      benzyloxy-4-methoxybenzaldehyde (1) as a starting material. The X-ray crystal
      diffraction structure of two compounds, racemic 9-benzyloxy-tetrabenazine (5) and
      the diastereomeric salt of compound 8, is also described for the first time in
      this article. The X-ray results and the chiral HPLC helped elucidate that
      compound 8 has an absolute configuration as 2R,3R,11bR. The crystal structure of
      racemic compound 5 contains two symmetry- independent molecules in the unit cell.
      Interestingly, while they are structural isomers, they are enantiomers, too,
      i.e., in solution, because they are not mirror images of each other in the
      crystal lattice. In order to elucidate the intermolecular interaction mechanism
      of the diastereomeric salt of compound 8, its crystal packing was investigated
      with regard to the weak interactions, such as salt bridge, OH...O and CH...O
      hydrogen bonds, and intermolecular CH...pi interaction. The results showed that
      the carbonyl-assisted salt bridges and the OH...O hydrogen bonds formed polar
      columns in the crystal structure of the diastereomeric salt of compound 8,
      resembling butterflies with open wings as viewed along the c-axis. These polar
      columns were extended to three-dimensional network by intermolecular CH...O
      hydrogen bonds and intermolecular CH...pi interactions.

PMID- 23532998
TI  - SpecDis: quantifying the comparison of calculated and experimental electronic
      circular dichroism spectra.
AB  - This article outlines theory and practice of the comparison of calculated and
      experimental electronic circular dichroism (ECD) curves to determine the absolute
      configuration of chiral molecules. The focus is on the evaluation of excited
      state calculations giving hints at the identification of the correct bandwidth
      and the application of the so-called "UV shift" as a correction factor. A
      similarity factor is introduced, which helps to quantify the degree of matching
      of curves. In addition, a few common errors are described that can be made during
      the measurements of ECD and UV spectra-and advice is given of how to avoid these
      mistakes. All equations mentioned in the article are implemented in our SpecDis
      software, which has been developed to rapidly compare calculated ECD and UV
      curves with experimental ones, and to produce graphics in publication quality.

PMID- 23532999
TI  - O-heterocyclic embeurekols from Embellisia eureka, an endophyte of Cladanthus
      arabicus.
AB  - Three new polyketides ((-)-1, (+)-1, and 2) were isolated from the EtOAc extract
      of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus
      arabicus (Asteraceae). The structures of these new compounds were determined on
      the basis of one- and two-dimensional NMR spectroscopy as well as by high
      resolution mass spectrometry. The absolute configurations of (-)-1, (+)-1, and 2
      were determined by TDDFT ECD calculations of solution conformers, online HPLC-ECD
      analysis, and the modified Mosher method.

PMID- 23533001
TI  - Measuring hazardous work and identifying risk factors for non-fatal injuries
      among children working in Philippine agriculture.
AB  - OBJECTIVES: Global consensus is lacking, especially among developing countries,
      on whether agricultural work is detrimental to children's health and safety. We
      aimed to measure the degree to which Philippine children working in agriculture
      have a higher risk of injury compared with children working in other industries,
      and to uncover potential risk factors for their non-fatal injuries. METHODS:
      Using the Philippine Survey of Children (SOC) 2001, we calculated injury
      incidence rates and relative risk measures across industries, and employed a
      multivariate logistic regression on the sample of working children in agriculture
      to ascertain the association of various exposures with the occurrence of work
      related injuries. RESULTS: Children working in agriculture had a fivefold risk of
      non-fatal injury compared to children working in other industries. Logistic
      regression indicated that the most robust risk factor for the occurrence of non
      fatal injury was the use of tools (OR = 3.12). CONCLUSIONS: The results of this
      study demonstrate agriculture to be a hazardous industry for children. Further
      research should focus on identifying the most dangerous tools and restricting
      their use.

PMID- 23533000
TI  - Genetic recombination in plant-infecting messenger-sense RNA viruses: overview
      and research perspectives.
AB  - RNA recombination is one of the driving forces of genetic variability in (+)
      strand RNA viruses. Various types of RNA-RNA crossovers were described including
      crosses between the same or different viral RNAs or between viral and cellular
      RNAs. Likewise, a variety of molecular mechanisms are known to support RNA
      recombination, such as replicative events (based on internal or end-to-end
      replicase switchings) along with non-replicative joining among RNA fragments of
      viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference
      are responsible for RNA fragmentation and trans-esterification reactions which
      are likely accountable for ligation of RNA fragments. Numerous host factors were
      found to affect the profiles of viral RNA recombinants and significant
      differences in recombination frequency were observed among various RNA viruses.
      Comparative analyses of viral sequences allowed for the development of
      evolutionary models in order to explain adaptive phenotypic changes and co
      evolving sites. Many questions remain to be answered by forthcoming RNA
      recombination research. (1) How various factors modulate the ability of viral
      replicase to switch templates, (2) What is the intracellular location of RNA-RNA
      template switchings, (3) Mechanisms and factors responsible for non-replicative
      RNA recombination, (4) Mechanisms of integration of RNA viral sequences with
      cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme
      activity. From an evolutionary stand point, it is not known how RNA viruses
      parasitize new host species via recombination, nor is it obvious what the
      contribution of RNA recombination is among other RNA modification pathways. We do
      not understand why the frequency of RNA recombination varies so much among RNA
      viruses and the status of RNA recombination as a form of sex is not well
      documented.

PMID- 23533002
TI  - Component alignment and functional outcome following computer assisted and jig
      based total knee arthroplasty.
AB  - BACKGROUND: Incorrect positioning of the implant and improper alignment of the
      limb following total knee arthroplasty (TKA) can lead to rapid implant wear,
      loosening, and suboptimal function. Studies suggest that alignment errors of > 3
      degrees  are associated with rapid failure and less satisfactory function.
      Computer navigated systems have been developed to enhance precision in
      instrumentation during surgery. The aim of the study was to compare component
      alignment following computer assisted surgery (CAS) and jig based TKA as well as
      functional outcome. MATERIALS AND METHODS: This is a prospective study of 100
      knees to compare computer-assisted TKA and jig-based surgery in relation to
      femoral and tibial component alignment and functional outcome. The postoperative
      x-rays (anteroposterior and lateral) of the knee and CT scanogram from hip to
      foot were obtained. The coronal alignment of the femoral and tibial components
      and rotational alignment of femoral component was calculated. Knee society score
      at 24 months was used to assess the function. RESULTS: Results of our study show
      that mean placement of the tibial component in coronal plane (91.3037 degrees )
      and sagittal planes (3.6058 degrees ) was significantly better with CAS. The
      difference was statistically insignificant in case of mean coronal alignment of
      the femoral components (90.34210 degrees  in navigation group and 90.5444 degrees
      in jig group) and in case of the mean femoral condylar twist angle (external
      rotation 2.3406 degrees  in navigation group versus 2.3593 degrees  in jig
      group). CONCLUSIONS: A significantly improved placement of the component was
      found in the coronal and sagittal planes of the tibial component by CAS. The
      placement of the components in the other planes was comparable with the values
      recorded in the jig-based surgery group. Functional outcome was not significantly
      different.

PMID- 23533004
TI  - Sustained release of simvastatin from premixed injectable calcium phosphate
      cement.
AB  - Locally applied simvastatin is known to promote bone regeneration; however, the
      lack of suitable delivery systems has restricted its clinical use. In this study
      we demonstrate for the first time the use of premixed acidic calcium phosphate
      cement (CPC) as a delivery system for water-solubilized simvastatin. Freeze-dried
      simvastatin beta-hydroxy acid (SVA) was added to the premixed cement paste in
      four different doses (1, 0.5, 0.25, and 0 mg SVA/g cement). The addition of the
      drug did not alter the cement setting time (38 min), compression strength (5.54
      MPa), or diametral tensile strength (2.62 MPa). In a release study conducted in
      phosphate buffered saline at 37 degrees C, a diffusion-controlled release was
      observed for over a week. Furthermore, the osteogenic effect of the released SVA
      was demonstrated in vitro. Cell proliferation, alkaline phosphatase activity, and
      mineralization were assayed after incubation with cement extracts. The lower
      doses of SVA (0.5 and 0.25 mg SVA/g cement) showed an approximately fourfold
      increase in mineralization as compared to the control. In conclusion, our
      findings suggest that premixed acidic CPC is a good option for local delivery of
      SVA, due to its ability of slowly releasing the drug, leading to a prolonged
      stimulation of osteogenesis.

PMID- 23533003
TI  - Significant modifications of the salivary proteome potentially associated with
      complications of Down syndrome revealed by top-down proteomics.
AB  - People with Down syndrome, a frequent genetic disorder in humans, have increased
      risk of health problems associated with this condition. One clinical feature of
      Down syndrome is the increased prevalence and severity of periodontal disease in
      comparison with the general population. Because saliva plays an important role in
      maintaining oral health, in the present study the salivary proteome of Down
      syndrome subjects was investigated to explore modifications with respect to
      healthy subjects. Whole saliva of 36 Down syndrome subjects, divided in the age
      groups 10-17 yr and 18-50 yr, was analyzed by a top-down proteomic approach,
      based on the high performance liquid chromatography-electrospray ionization-MS
      analysis of the intact proteins and peptides, and the qualitative and
      quantitative profiles were compared with sex- and age-matched control groups. The
      results showed the following interesting features: 1) as opposed to controls, in
      Down syndrome subjects the concentration of the major salivary proteins of gland
      origin did not increase with age; as a consequence concentration of acidic
      proline rich proteins and S cystatins were found significantly reduced in older
      Down syndrome subjects with respect to matched controls; 2) levels of the
      antimicrobial alpha-defensins 1 and 2 and histatins 3 and 5 were significantly
      increased in whole saliva of older Down syndrome subjects with respect to
      controls; 3) S100A7, S100A8, and S100A12 levels were significantly increased in
      whole saliva of Down syndrome subjects in comparison with controls. The increased
      level of S100A7 and S100A12 may be of particular interest as a biomarker of early
      onset Alzheimer's disease, which is frequently associated with Down syndrome. 

PMID- 23533005
TI  - Common obesity risk alleles in childhood attention-deficit/hyperactivity
      disorder.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate
      of obesity than children without ADHD. Obesity risk alleles may overlap with
      those relevant for ADHD. We examined whether risk alleles for an increased body
      mass index (BMI) are associated with ADHD and related quantitative traits
      (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles
      of single nucleotide polymorphisms (SNPs) in a genome-wide association study
      (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and
      performed in silico analyses of the SNPs in an ADHD meta-analysis comprising
      2,064 trios, 896 independent cases, and 2,455 controls. In the German sample
      rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type
      motif 3) was associated with ADHD risk (OR: 1.39; P = 3.4 * 10(-4) ; Pcorr  =
      0.01). In the meta-analysis data we found rs6497416 in the intronic region of the
      GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P = 7.2 *
      10(-4) ; Pcorr  = 0.02) as a risk allele for ADHD. GPRC5B belongs to the
      metabotropic glutamate receptor family, which has been implicated in the etiology
      of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine
      6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas
      markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell
      adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta
      analysis data, MAP2K5 was associated with inattention, GPRC5B with
      hyperactivity/impulsivity and inattention and CADM2 with
      hyperactivity/impulsivity. Our results justify further research on the
      elucidation of the common genetic background of ADHD and obesity.

PMID- 23533006
TI  - The Evangelismos hospital central nervous system tumor registry: Analysis of 1414
      cases (1998-2009).
AB  - BACKGROUND: The Evangelismos Hospital central nervous system (CNS) Tumor Registry
      represents the current effort of the Departments of Neurosurgery and Pathology to
      collect data for primary and metastatic CNS tumor patients. In the present study,
      12-year hospital data (1998-2009) were reviewed and analyzed. METHODS: Patients
      that underwent surgery for CNS tumors for the first time were identified.
      Histologically confirmed tumor rates by age and gender were compared. Time trends
      in annual rates for specific tumor types were investigated. In-hospital mortality
      rates and length of hospital stay were analyzed by age and gender and their
      putative variations across the study period investigated. RESULTS: A total of
      1414 patients (age 15-89 years) were identified. The most frequently encountered
      histologies were gliomas and meningiomas, accounting for, respectively, 32.8% and
      29.1% of the total sample. A greater proportion of meningiomas was found in
      women; the proportion of glioblastomas and metastatic tumors, as well as of mixed
      gliomas, were greater in men. Increased rates of glioblastoma and meningioma with
      advancing age at diagnosis were also apparent. There were no significant
      variations in time trends for specific tumor types. In-hospital mortality was
      significantly higher for older patients (>=70 years). An increase in the length
      of hospital stay was apparent between the first and middle third of the study
      period. CONCLUSIONS: Analysis of tumor rates in relation to age at diagnosis and
      gender showed significant bias in accordance with salient literature. Available
      data indicated no significant variations in time trends for specific tumor types
      across the study period, while an adverse effect of advanced age on in-hospital
      mortality was shown. The present findings can guide the formulation of future
      treatment programs and preventive strategies and provide the basis for further
      intra- and/or interdepartmental research.

PMID- 23533007
TI  - Clinical decision making in the treatment of complex PTSD and substance misuse.
AB  - Treating clients with complex posttraumatic stress disorder (PTSD) who also
      misuse substances presents a number of clinical challenges. The nature of complex
      PTSD is that we are faced with the far-reaching consequences of early and
      prolonged trauma on clients' lives, typically interfering with a host of
      emotional, relational, and functional capacities. Often substance misuse has
      become an offshoot of this experience, initially an "adaptive" response to
      unbearable circumstances, but over time exacerbating client dysfunction, at times
      leading to revictimization, and frequently culminating in a substance use
      disorder. Many clinicians feel overwhelmed in the face of this myriad of
      problems. This article provides an overview of some of the clinical choice points
      facing clinicians in this work: Where do we start? How do we proceed? What do we
      treat first? How do we handle a dysregulated client? The article attempts to
      provide some guidance about how to approach these multifaceted decisions, with an
      emphasis on attending to comorbidity, to assist clinicians in providing symptom
      focused treatment for this complex population.

PMID- 23533008
TI  - To binge or not to binge: binge drinking disrupts glucose homeostasis by
      impairing hypothalamic but not liver insulin signaling.

PMID- 23533009
TI  - Can antipsychotics improve social cognition in patients with schizophrenia?
AB  - Social cognition is described as the higher mental processes that are engaged
      while people store, process, and use social information to make sense of
      themselves and others. Aspects of social cognition include emotion perception,
      social cue interpretation, attribution style, and theory of mind, all of which
      appear disordered in schizophrenia. Such social cognitive deficits are believed
      to be important predictors of functional outcome in schizophrenia, therefore they
      may represent a crucial treatment target. Few studies have evaluated the
      influence of antipsychotic treatment on these deficits. The purpose of this
      review is to examine the relationship between antipsychotic treatment and social
      cognition, whether antipsychotics improve social cognitive function, and if so to
      explore differential medication effects. Comprehensive searches of PsycINFO and
      MEDLINE/PUBMED were conducted to identify relevant published manuscripts. Fifteen
      relevant papers published in English were found, describing original studies. On
      the basis of this review, we have drawn the following conclusions: first, the
      results do not engender optimism for the possibility that antipsychotic drugs can
      specifically facilitate social recovery. Second, the actions of antipsychotics on
      social cognition are inconclusive, due to lack of standardization across research
      groups, leading to inconsistencies between study designs, methods used, and
      medication dosages. Third, large-scale longitudinal investigations are needed to
      explore the unclear relationships between social cognition, symptoms, and
      functional outcome. Other non-pharmacological treatments focusing on training
      patients in the social cognitive areas may hold more promise.

PMID- 23533010
TI  - Safety and efficacy of intravenous lacosamide for adjunctive treatment of
      refractory status epilepticus: a comparative cohort study.
AB  - BACKGROUND: Refractory status epilepticus (RSE) is an emergency with high
      mortality requiring neurointensive care. Treatment paradigms include first
      generation antiepileptic drugs (AEDs) and anesthetics. Lacosamide (LCM) is a new
      AED, holding promise as a potent treatment option for RSE. High-level evidence
      regarding safety and efficacy in the treatment of RSE is lacking. OBJECTIVE: The
      objective of the study was to evaluate the safety profile and efficacy of
      intravenous (i.v.) LCM as an add-on treatment in adult RSE patients. METHODS: All
      consecutive RSE patients treated in the intensive care units (ICUs) of an
      academic tertiary care center between 2005 and 2011 were included. Severity of
      status epilepticus (SE) was graded by the SE Severity Scale (STESS), and SE
      etiology was categorized according to the guidelines of the International League
      Against Epilepsy (ILAE). Outcomes were seizure control, RSE duration, and death.
      RESULTS: Of 111 RSE patients, 53 % were treated with LCM. Twenty-five patients
      with hypoxic-ischemic encephalopathy were excluded. Mortality was 30 %. Mean
      number of AEDs, duration, severity, and etiology of SE, as well as critical
      medical conditions did not differ between patients with and without LCM. While
      age tended to be higher, critical interventions, such as the use of anesthetics
      and mechanical ventilation, tended to be less frequent in patients with LCM.
      Seizure control tended to be achieved more frequently in patients with LCM (odds
      ratio, OR 2.34, 95 % CI 0.5-10.1, p = 0.252). Among patients with LCM, 51 %
      received LCM as the last AED (including hypoxic-ischemic encephalopathy),
      allowing the reasonable assumption that LCM was responsible for seizure control,
      which was achieved in 91 %. Multivariable analysis revealed a decreased mortality
      in patients with LCM (OR 0.34, 95 % CI 0.1-0.9, p = 0.035). A possible confounder
      in this context was the implementation of continuous video-electroencephalography
      (EEG) monitoring 6 months prior to the first use of i.v. LCM. There were no
      serious LCM-related adverse events. CONCLUSION: LCM had a favorable safety
      profile as adjunctive treatment for RSE. Its use was associated with decreased
      mortality of RSE-a finding that might have been confounded by the implementation
      of continuous video-EEG monitoring in the ICU prior to the use of i.v. LCM,
      leading to heightened awareness as well as earlier diagnosis and treatment of SE.
      Randomized trials are warranted to further strengthen the evidence of efficacy of
      LCM for RSE treatment.

PMID- 23533011
TI  - Antipsychotic-induced metabolic and cardiovascular side effects in schizophrenia:
      a novel mechanistic hypothesis.
AB  - The use of antipsychotics is hindered by the frequent occurrence of metabolic and
      cardiovascular side effects, resulting in worsened quality of life and greater
      mortality as a result of cardiovascular and cerebrovascular disorders in
      schizophrenia patients than the comparable general population. The various
      antipsychotics induce extrapyramidal symptoms, impaired glucose and lipid
      metabolism, weight gain, hypertension and arrhythmias, with variable frequency.
      Second-generation antipsychotics appear to have several advantages over first
      generation antipsychotics, including a claimed better action on cognitive
      function and the negative symptoms of schizophrenia, and lower frequency of
      extrapyramidal side effects; however, their use is associated with a greater
      frequency of metabolic and cardiovascular disturbances. The mechanisms of these
      important side effects are not well understood, and generic approaches
      (psychoeducational programmes and symptomatic therapies) have been proposed to
      limit their severity. Extensive data from the literature indicate that autonomic
      nervous system dysfunction--intrinsic to schizophrenia and strongly exacerbated
      by antipsychotic treatment--is the cause of the pervasive metabolic and vascular
      dysfunctions associated with schizophrenia. In this article, we marshal further
      literature data to argue that the metabolic and cardiovascular side effects of
      antipsychotics are primarily mediated by their ability to block peripheral
      dopamine receptors, which physiologically modulate sympathetic activity. We also
      propose that these effects might be overcome by providing peripheral dopaminergic
      stimulation.

PMID- 23533012
TI  - Gallium(III)-catalyzed cycloisomerization approach to the diterpenoid alkaloids:
      construction of the core structure for the hetidines and hetisines.

PMID- 23533013
TI  - Feasibility of a nurse-led in-home cognitive behavioral program to manage
      concerns about falls in frail older people: a process evaluation.
AB  - Concerns about falls and related avoidance of activities are common problems
      among older people living in the community. In this study we examined the
      feasibility and acceptability of AMB-Home (the Dutch in-home version of A Matter
      of Balance), a nurse-led in-home cognitive behavioral program developed for frail
      community-living older people with concerns about falls and related activity
      avoidance. The multicomponent program consisted of seven individual sessions,
      including three home visits and four telephone contacts. Data were collected from
      eight nurses and 194 participants. Generally, the program was considered
      acceptable and feasible by both the nurses and the participants. When AMB-Home
      turns out to be effective, the implementation of a fine-tuned version of this in
      home program in regular health care, would be a natural next step.

PMID- 23533014
TI  - Methacrylate-endcapped caprolactone and FM19G11 provide a proper niche for spinal
      cord-derived neural cells.
AB  - Spinal cord injury (SCI) is a cause of paralysis. Although some strategies have
      been proposed to palliate the severity of this condition, so far no effective
      therapies have been found to reverse it. Recently, we have shown that acute
      transplantation of ependymal stem/progenitor cells (epSPCs), which are spinal
      cord-derived neural precursors, rescue lost neurological function after SCI in
      rodents. However, in a chronic scenario with axon repulsive reactive scar, cell
      transplantation alone is not sufficient to bridge a spinal cord lesion, therefore
      a combinatorial approach is necessary to fill cavities in the damaged tissue with
      biomaterial that supports stem cells and ensures that better neural integration
      and survival occur. Caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) is a
      monomer [obtained as a result of epsilon-caprolactone and 2-hydroxyethyl
      methacrylate (HEMA) ring opening/esterification reaction], which can be processed
      to obtain a porous non-toxic 3D scaffold that shows good biocompatibility with
      epSPC cultures. epSPCs adhere to the scaffolds and maintain the ability to expand
      the culture through the biomaterial. However, a significant reduction of cell
      viability of epSPCs after 6 days in vitro was detected. FM19G11, which has been
      shown to enhance self-renewal properties, rescues cell viability at 6 days.
      Moreover, addition of FM19G11 enhances the survival rates of mature neurons from
      the dorsal root ganglia when cultured with epSPCs on 3D CLMA scaffolds. Overall,
      CLMA porous scaffolds constitute a good niche to support neural cells for cell
      transplantation approaches that, in combination with FM19G11, offer a new
      framework for further trials in spinal cord regeneration.

PMID- 23533015
TI  - Prolyl hydroxylase 3 inhibited the tumorigenecity of gastric cancer cells.
AB  - Gastric cancer is one of the most common malignancies and the second leading
      cause of cancer-related death in the world, and it is very urgent to develop
      novel therapeutic strategies. Although HIF-1alpha is the most highly
      characterized target of prolyl hydroxylase 3 (PHD3), PHD3 has been shown to
      regulate several signal pathways independent of HIF-1alpha. Here, we found that
      the expression of PHD3 was decreased in the clinical gastric cancer samples and
      reversely correlated with tumor size and tumor stage. Over-expression of PHD3 in
      the gastric cancer cells significantly inhibited cell growth in vitro and in
      vivo, while knockdown the expression of PHD3 promoted the tumorigenecity of
      gastric cancer cells. Mechanistically, it showed that PHD3 downregulated the
      expression of beta-catenin and inhibited beta-catenin/T-cell factor (TCF)
      signaling. Taken together, our findings demonstrate that PHD3 inhibits gastric
      cancer by suppressing the beta-catenin/TCF signaling and PHD3 might be an
      important therapeutic target in gastric cancer.

PMID- 23533016
TI  - More than training: Community-based participatory research to reduce injuries
      among hispanic construction workers.
AB  - BACKGROUND: Workplace mortality and severe injury are disproportionately
      distributed among foreign born and Hispanic construction workers. Worker Centers
      (WCs) provide services and advocacy for low-wage workers and a way for
      investigators to reach them. The goal of this project is to prevent occupational
      injuries by increasing awareness of hazards and self-efficacy among foreign born,
      Hispanic construction workers and by expanding the agenda of WCs to include
      occupational health and safety (H&S). METHODS: Investigators partnered with eight
      WCs in seven cities to train worker leaders to deliver a modified OSHA 10-hr
      curriculum to their peers. RESULTS: Thirty-two worker leaders trained 446 workers
      over 3 years. There was a demonstrated improvement in knowledge, hazard
      identification, self-efficacy, and sustainable H&S activities. CONCLUSIONS: This
      study provides evidence for successful implementation of a training intervention
      for low wage, low literacy Hispanic construction workers using a community-based
      participatory research approach.

PMID- 23533018
TI  - Sr4Fe6O12: low-temperature Fe(2+)-Fe3+ charge order within pairs of edge-linked
      tetrahedra.

PMID- 23533017
TI  - Evaluation of blood cell attachment on Er: YAG laser applied root surface using
      scanning electron microscopy.
AB  - BACKGROUND: Periodontal regeneration is dependent on the uninterrupted adhesion,
      maturation and absorption of fibrin clots to a periodontally compromised root
      surface. The modification of the root surface with different agents has been used
      for better fibrin clot formation and blood cell attachment. It is known that
      Er:YAG laser application on dentin removes the smear layer succesfully. AIM: The
      aim of this study is to observe blood cell attachment and fibrin network
      formation following ER:YAG laser irradiation on periodontally compromised root
      surfaces in comparison to chemical root conditioning techniques in vitro.
      MATERIALS AND METHODS: 40 dentin blocks prepared from freshly extracted
      periodontally compromised hopeless teeth. Specimens were divided in 5 groups;
      those applied with PBS, EDTA, Citric acid and Er:YAG. They were further divided
      into two groups: those which had received these applications, and the control
      group. The specimens were evaluated with scanning electron microscope and
      micrographs were taken. Smear layer and blood cell attachment scoring was
      performed. RESULTS: In the Er:YAG laser applied group, smear layer were totally
      removed. In the blood applied specimens, better fibrin clot formation and blood
      cell attachment were observed in the Er:YAG group. In the group that had been
      applied with citric acid, the smear layer was also removed. The smear layer could
      not be fully removed in the EDTA group. CONCLUSION: Er:YAG laser application on
      the root dentin seems to form a suitable surface for fibrin clot formation and
      blood cell attachment. Further clinical studies to support these results are
      necessitated.

PMID- 23533019
TI  - Tourniquet-Free Hand Surgery Using the One-per-Mil Tumescent Technique.
AB  - BACKGROUND: A pneumatic tourniquet is generally used to achieve a bloodless
      operation field in hand surgery. However, this has changed with tumescent
      solution-based wide-awake surgery. This study is a preliminary prospective case
      series study to elaborate the formula and indications of the tumescent technique
      in hand surgery without a tourniquet. METHODS: Seven patients (age range, 4
      months to 37 years) underwent hand or upper extremity surgery for conditions such
      as nerve palsy, electric burn defect, fingertip injury, contracture, constriction
      ring syndrome, or acrosyndactyly. A "one-per-mil" tumescent solution (epinephrine
      1:1,000,000+20 mg lidocaine/50 mL saline) was used to create a bloodless
      operating field without a tourniquet. Observation was performed to document the
      amount of solution injected, the operation field clarity, and the postoperative
      pain. RESULTS: The "one per mil" epinephrine solution showed an effective
      hemostatic effect. The tumescent technique resulted in an almost bloodless
      operation field in the tendon and in the constriction ring syndrome surgeries,
      minimal bleeding in the flap and contracture release surgeries, and acceptable
      bleeding in acrosyndactyly surgery. The amount of solution injected ranged from
      5.3 to 60 mL. No patient expressed significant postoperative pain. Flap surgeries
      showed mixed results. One flap was lost, while the others survived. CONCLUSIONS:
      Epinephrine 1:1,000,000 in saline solution is a potential replacement for a
      tourniquet in hand surgery. Further studies are needed to delineate its safety
      for flap survival.

PMID- 23533020
TI  - Results of uncemented distal locked prosthesis in revision hip arthroplasty with
      proximal femoral bone loss: A retrospective study.
AB  - INTRODUCTION: Management of bone loss is a challenge in revision total hip
      arthroplasty (THA). A retrospective review was performed to study the use of
      uncemented distal locked prosthesis in cases with proximal femoral bone loss.
      MATERIALS AND METHODS: Uncemented stems with distal interlocking were used in 65
      hips during revision THAs with 38 hips having Paprosky IIIB/IV defects between
      January 1998 and February 2004. There were 48 males and 17 females in the study
      with an average age of 53 years (range 30-80 years). Radiographic and clinical
      outcome evaluation using the Harris hip score (HHS) were performed. RESULTS: AN
      IMPROVEMENT IN HHS (MEAN: 33 points) was observed at final followup (mean: 9
      years). Regeneration of proximal bone stock was observed without signs of
      loosening or subsidence and none of the stems were revised. Three patients
      developed recurrent dislocation while one had a stem subsidence of 1cm following
      removal of interlocking bolts. CONCLUSION: Uncemented distal locked prosthesis
      provide adequate stability in revision THA, aiding the reconstruction of bony
      deficiencies while avoiding the disadvantages of fully porous or cemented
      implants.

PMID- 23533021
TI  - Genotype-phenotype relationships in the low-phospholipid-associated
      cholelithiasis syndrome: a study of 156 consecutive patients.
AB  - The low-phospholipid-associated cholelithiasis syndrome (LPAC; OMIM 171060) is a
      peculiar form of intrahepatic cholelithiasis occurring in young adults,
      associated with ABCB4/MDR3 gene sequence variations. Our aim was to determine the
      genotype-phenotype relationships in 156 consecutive patients with the criteria of
      LPAC syndrome. A variant was detected in 79 (61 missense and 18 truncating
      sequence variants), 63 being monoallelic. The clinical features (age at onset,
      high prevalence in women, frequency and severity of acute and chronic
      complications, intrahepatic cholestasis of pregnancy [ICP]) were similar in the
      patients with or without ABCB4 gene sequence variation. Truncating variations
      were associated with an earlier onset of symptoms both in women and men. Acute
      and chronic biliary complications were variant-independent. Half of the women who
      had pregnancy developed ICP. The frequency of ICP and fetal complications were
      similar in patients with missense and truncating variants. CONCLUSION: The LPAC
      syndrome is more frequent in women and highly associated with ICP. Half of the
      patients harbored missense or truncating variants of the ABCB4 gene. The
      characteristics of the patients without detectable variant are similar to those
      with variant, indicating that yet unexplored regions of the ABCB4 and other genes
      may be involved.

PMID- 23533023
TI  - The NUITM-KEMRI P3 Laboratory in Kenya: Establishment, Features, Operation and
      Maintenance.
AB  - A biocontainment facility is a core component in any research setting due to the
      services it renders towards comprehensive biosafety observance. The NUITM-KEMRI
      P3 facility was set up in 2007 and has been actively in use since 2010 by
      researchers from this and other institutions. A number of hazardous agents have
      been handled in the laboratory among them MDR-TB and yellow fever viruses. The
      laboratory has the general physical and operational features of a P3 laboratory
      in addition to a number of unique features, among them the water-air filtration
      system, the eco-mode operation feature and automation of the pressure system that
      make the facility more efficient. It is equipped with biosafety and emergency
      response equipments alongside common laboratory equipments, maintained regularly
      using daily, monthly and yearly routines. Security and safety is strictly
      observed within the facility, enhanced by restricted entry, strict documentation
      and use of safety symbols. Training is also engrained within the operation of the
      laboratory and is undertaken and evaluated annually. Though the laboratory is in
      the process of obtaining accreditation, it is fully certified courtesy of the
      manufactures' and constructed within specified standards.

PMID- 23533022
TI  - The influence of environmental hazard maps on risk beliefs, emotion, and health
      related behavioral intentions.
AB  - To test a theoretical explanation of how attributes of mapped environmental
      health hazards influence health-related behavioral intentions and how beliefs and
      emotion mediate the influences of attributes, 24 maps were developed that varied
      by four attributes of a residential drinking water hazard: level, proximity,
      prevalence, and density. In a factorial design, student participants (N = 446)
      answered questions about a subset of maps. Hazard level and proximity had the
      largest influences on intentions to test water and mitigate exposure. Belief in
      the problem's seriousness mediated attributes' influence on intention to test
      drinking water, and perceived susceptibility mediated the influence of attributes
      on intention to mitigate risk. Maps with carefully illustrated attributes of
      hazards may promote appropriate health-related risk beliefs, intentions, and
      behavior.

PMID- 23533024
TI  - One-year experiment on the physiological response of the Mediterranean crustose
      coralline alga, Lithophyllum cabiochae, to elevated pCO2 and temperature.
AB  - The response of respiration, photosynthesis, and calcification to elevated pCO2
      and temperature was investigated in isolation and in combination in the
      Mediterranean crustose coralline alga Lithophyllum cabiochae. Algae were
      maintained in aquaria during 1 year at near-ambient conditions of irradiance, at
      ambient or elevated temperature (+3 degrees C), and at ambient (ca. 400 MUatm) or
      elevated pCO2 (ca. 700 MUatm). Respiration, photosynthesis, and net calcification
      showed a strong seasonal pattern following the seasonal variations of temperature
      and irradiance, with higher rates in summer than in winter. Respiration was
      unaffected by pCO2 but showed a general trend of increase at elevated temperature
      at all seasons, except in summer under elevated pCO2. Conversely, photosynthesis
      was strongly affected by pCO2 with a decline under elevated pCO2 in summer,
      autumn, and winter. In particular, photosynthetic efficiency was reduced under
      elevated pCO2. Net calcification showed different responses depending on the
      season. In summer, net calcification increased with rising temperature under
      ambient pCO2 but decreased with rising temperature under elevated pCO2.
      Surprisingly, the highest rates in summer were found under elevated pCO2 and
      ambient temperature. In autumn, winter, and spring, net calcification exhibited a
      positive or no response at elevated temperature but was unaffected by pCO2. The
      rate of calcification of L. cabiochae was thus maintained or even enhanced under
      increased pCO2. However, there is likely a trade-off with other physiological
      processes. For example, photosynthesis declines in response to increased pCO2
      under ambient irradiance. The present study reports only on the physiological
      response of healthy specimens to ocean warming and acidification, however, these
      environmental changes may affect the vulnerability of coralline algae to other
      stresses such as pathogens and necroses that can cause major dissolution, which
      would have critical consequence for the sustainability of coralligenous habitats
      and the budgets of carbon and calcium carbonate in coastal Mediterranean
      ecosystems.

PMID- 23533026
TI  - An inverse relationship between injuries and fatalities: what is surprising--and
      what is not.

PMID- 23533025
TI  - Baseline thyroid indices and the subsequent response to citalopram treatment, a
      pilot study.
AB  - The lack of reliable outcome predictors and the delayed onset of therapeutic
      response to antidepressants are among the clinical challenges in the treatment of
      depression. Identifying clinical correlates associated with antidepressant
      response would reduce symptom severity and morbidity for patients with
      depression. Twenty-three subjects with major depression were treated with
      citalopram 20 mg/day in a 6-week open trial and were also simultaneously
      randomized to either adjunctive triiodothyronine (T3) 25 MUg BID (n = 7),
      pindolol 5 mg BID (n = 8), or placebo (n = 8). Baseline thyroid-stimulating
      hormone (TSH), FT4, FT3, and TT3 were measured for potential relationships to
      treatment response across groups. In males only, there was a significant inverse
      correlation between baseline free T4 and time to response (r = -0.7, P = 0.034).
      In both males and females across all treatment conditions, as measured by Kaplan
      Meier (K-M) maintenance failure time, baseline TSH below the mean (1.5 ng/dL) was
      associated with a shorter time to response (50% reduction in Montgomery and
      Asberg Depression Rating Scale [MADRS] score) (chi(2) = 4.53, df = 1, P = 0.03).
      Patients with baseline TSH above the mean were less likely to reach full
      remission (MADRS <= 7) (chi(2) = 4.38, df = 1, P = 0.03). No significant
      differences between groups emerged in the mean response time. Baseline thyroid
      function, as measured by serum free T4 and TSH, may predict a patient's response
      time to antidepressant treatment with citalopram.

PMID- 23533027
TI  - Minding the ecological body: neuropsychoanalysis and ecopsychoanalysis.
AB  - Neuropsychoanalysis explores experimentally and theoretically the philosophically
      ancient discussion of the relation of mind and body, and seems well placed to
      overcome the problem of a "mindless" neuroscience and a "brainless" psychology
      and psychotherapy, especially when combined with a greater awareness that the
      body itself, not only the brain, provides the material substrate for the emergent
      phenomenon we call mind. However, the mind-brain-body is itself situated within a
      complex ecological world, interacting with other mind-brain-bodies and the "non
      human environment." This occurs both synchronically and diachronically as the
      organism and its environment (living and non-living) interact in highly complex
      often non-linear ways. Psychoanalysis can do much to help unmask the anxieties,
      deficits, conflicts, phantasies, and defenses crucial in understanding the human
      dimension of the ecological crisis. Yet, psychoanalysis still largely remains not
      only a "psychology without biology," which neuropsychoanalysis seeks to remedy,
      but also a "psychology without ecology." Ecopsychoanalysis (Dodds, 2011b; Dodds
      and Jordan, 2012) is a new transdisciplinary approach drawing on a range of
      fields such as psychoanalysis, psychology, ecology, philosophy, science,
      complexity theory, esthetics, and the humanities. It attempts to play with what
      each approach has to offer in the sense of a heterogeneous assemblage of ideas
      and processes, mirroring the interlocking complexity, chaos, and turbulence of
      nature itself. By emphasizing the way the mind-brain-body studied by
      neuropsychoanalysis is embedded in wider social and ecological networks,
      ecopsychoanalysis can help open up the relevance of neuropsychoanalysis to wider
      fields of study, including those who are concerned with what Wilson (2003) called
      "the future of life."

PMID- 23533028
TI  - Molecular and clinical characterization of 25 individuals with exonic deletions
      of NRXN1 and comprehensive review of the literature.
AB  - This study aimed to elucidate the observed variable phenotypic expressivity
      associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest
      cohort of patients with NRXN1 exonic deletions described to date and by
      comprehensively reviewing all comparable copy number variants in all disease
      cohorts that have been published in the peer reviewed literature (30 separate
      papers in all). Assessment of the clinical details in 25 previously undescribed
      individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic
      features consisting of moderate to severe intellectual disability (91%), severe
      language delay (81%), autism spectrum disorder (65%), seizures (43%), and
      hypotonia (38%). These showed considerable overlap with previously reported NRXN1
      deletion associated phenotypes in terms of both spectrum and frequency. However,
      we did not find evidence for an association between deletions involving the beta
      isoform of neurexin-1 and increased head size, as was recently published in four
      cases with a deletion involving the C-terminus of NRXN1. We identified additional
      rare copy number variants in 20% of cases. This study supports a pathogenic role
      for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The
      additional rare copy number variants identified may act as possible phenotypic
      modifiers as suggested in a recent digenic model of neurodevelopmental disorders.

PMID- 23533030
TI  - [Fascinating internal medicine. A personal viewpoint].

PMID- 23533031
TI  - [Acute limb ischemia].

PMID- 23533032
TI  - [Hormones and the critically ill].

PMID- 23533033
TI  - [Pharmacologic treatment of heart failure in the elderly].

PMID- 23533034
TI  - [Metastatic prostate cancer: new insights and developments].

PMID- 23533035
TI  - [Intestinal protozoa infections].

PMID- 23533036
TI  - [Physical therapy in the critically ill].

PMID- 23533037
TI  - [Contrast-induced nephropathy].

PMID- 23533029
TI  - Expanding roles for CD4 T cells and their subpopulations in tumor immunity and
      therapy.
AB  - The importance of CD4 T cells in orchestrating the immune system and their role
      in inducing effective T cell-mediated therapies for the treatment of patients
      with select established malignancies are undisputable. Through a complex and
      balanced array of direct and indirect mechanisms of cellular activation and
      regulation, this functionally diverse family of lymphocytes can potentially
      promote tumor eradication, long-term tumor immunity, and aid in establishing
      and/or rebalancing immune cell homeostasis through interaction with other immune
      cell populations within the highly dynamic tumor environment. However, recent
      studies have uncovered additional functions and roles for CD4 T cells, some of
      which are independent of other lymphocytes, that can not only influence and
      contribute to tumor immunity but paradoxically promote tumor growth and
      progression. Here, we review the recent advances in our understanding of the
      various CD4 T cell lineages and their signature cytokines in disease progression
      and/or regression. We discuss their direct and indirect mechanistic interplay
      among themselves and with other responding cells of the antitumor response, their
      potential roles and abilities for "plasticity" and memory cell generation within
      the hostile tumor environment, and their potentials in cancer treatment and
      immunotherapy.

PMID- 23533038
TI  - [Cardiovascular morbidity and mortality in renal diseases].

PMID- 23533039
TI  - [Tuberculosis: new treatment options and updated recommendations].

PMID- 23533040
TI  - [What's new in connective tissue diseases?].

PMID- 23533041
TI  - [Contrast-enhanced endoscopic ultrasound in the diagnosis of pancreatic
      diseases].
AB  - The European Federation of Societies for Ultrasound in Medicine and Biology
      (EFSUMB) recently introduced guidelines on the use of contrast enhanced
      ultrasound (CEUS). The so-called non-liver guidelines included clinical
      recommendations on the use of CEUS in pancreatic diseases. This article focuses
      on the application of endoscopic ultrasound in the evaluation of pancreatic
      neoplasia to highlight the importance of CEUS in daily routine.

PMID- 23533042
TI  - [52-year-old man with acute abdomen. Pneumatosis intestinalis].

PMID- 23533043
TI  - [Cerebral listeria abscess in a patient with gastric cancer].
AB  - HISTORY AND PRESENTATION ON ADMISSION: A 70-year-old woman with a history of
      gastric cancer and palliative chemotherapy was admitted with disturbed
      consciousness. INVESTIGATIONS: The cranial CT showed a tumor in the left
      parietocccipital region so that a cerebral metastasis was suspected. However
      further investigations including cranial MRT, liquor and blood culture collection
      showed that the immunocompromised patient suffered from a Listeria monocytogenes
      sepsis with subsequent meningitis and a cerebral abscess. TREATMENT AND COURSE:
      During an antibiotic treatment with ampicillin and gentamycin a rapid
      neurological improvement and normalization of the liquor findings was achieved.
      CONCLUSIONS: Listeria monocytogenes is a rare but relevant cause of systemic
      inflammations in immunocompromised patients. The differentiation between cerebral
      abscess and metastasis in cancer patients can be complex but is important
      concerning differential therapeutic approaches.

PMID- 23533044
TI  - [Perspectives on immunotherapy for hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide with a
      high mortality. Available therapeutical options are limited, thus the development
      of new, innovative therapeutic strategies is crucial. Based on the immune
      system's antitumoral effect, immunotherapy is a promising new treatment option.
      Specific antitumoral T-cell responses can be detected in patients with HCC,
      however, their impact on tumor control seems to be rather weak. Various different
      immunosuppressive mechanisms seem to contribute to the failure of tumor-specific
      T-cell responses. Thus, the aim of immunotherapeutic strategies is to address
      these mechanisms of T-cell failure and to induce new or to boost existing
      antitumoral immune responses.

PMID- 23533045
TI  - [Rheumatoid arthritis - cardiovascular risk is high, but manageable].

PMID- 23533046
TI  - [Rheumatoid arthritis - cardiovascular risk is high, but manageable].

PMID- 23533047
TI  - Papilla regeneration by injectable stem cell therapy with regenerative medicine:
      long-term clinical prognosis.
AB  - Black triangle (BT), an open interproximal space between teeth, can cause
      aesthetic concerns, food impaction, phonetic difficulties and periodontitis. The
      aim of this study was to determine the possibility and long-term prognosis of
      novel papilla regeneration with regenerative medicine, i.e. tissue-engineered
      papilla (TEP), and to investigate the potential of a tissue-engineering method
      for soft-tissue augmentation, especially aesthetic improvement of BT, with
      mesenchymal stem cells (MSCs) as the isolated cells, platelet-rich plasma (PRP)
      as the growth factor and hyaluronic acid (HA) as the scaffold. The parameters
      were assessed from a clinical point of view by measuring the distance from the
      tip of the interproximal papilla to the base of the contact area in each study
      region. The mean volumes, operation times and follow-up periods of TEP were 1.32
      +/- 0.25 ml, 2.2 +/- 1.62 times and 55.3 +/- 17.7 months; the mean improved BT
      values were 2.55 +/- 0.89 mm. An aesthetic improvement was achieved. TEP was able
      to provide aesthetic improvement of black triangle and predictable results, and
      could emerge as another novel option for periodontal regenerative therapy in
      periodontal diseases.

PMID- 23533048
TI  - Adherence to medication is a more important contributor to viral breakthrough in
      chronic hepatitis B patients treated with entecavir than in those with
      Lamivudine.
AB  - Viral breakthrough is related to poor adherence to medication in some chronic
      hepatitis B patients treated with nucleos(t)ide analogues (NAs). Our study aimed
      to examine how adherence to medication is associated with viral breakthrough in
      patients treated with NAs. A total of 203 patients (135 ETV and 68 LAM) were
      analyzed in this retrospective analysis. Physical examination, serum liver enzyme
      tests, and hepatitis B virus marker tests were performed at least every 3 months.
      We reviewed medical records and performed medical interviews regarding to
      patients' adherence to medication. Adherence rates <90% were defined as poor
      adherence in the present study. Cumulative viral breakthrough rates were lower in
      the ETV-treated patients than in the LAM-treated patients (P<0.001). Seven ETV
      treated (5.1%) and 6 LAM-treated patients (8.8%) revealed poor adherence to
      medication (P=0.48). Among ETV-treated patients, 4 (3.1%) of 128 patients without
      poor adherence experienced viral breakthrough and 3 (42.8%) of 7 patients with
      poor adherence experienced viral breakthrough (P<0.001). Only 3 of 38 (7.8%) LAM
      treated patients with viral breakthrough had poor adherence, a lower rate than
      the ETV-treated patients (P=0.039). Nucleoside analogue resistance mutations were
      observed in 50.0% of ETV- and 94.1% of LAM-treated patients with viral
      breakthrough (P=0.047). Viral breakthrough associated with poor adherence could
      be a more important issue in the treatment with especially stronger NAs, such as
      ETV.

PMID- 23533049
TI  - Nelfinavir suppresses insulin signaling and nitric oxide production by human
      aortic endothelial cells: protective effects of thiazolidinediones.
AB  - BACKGROUND: In human immunodeficiency virus 1 (HIV-1)-infected individuals,
      exposure to a protease inhibitor (PI)-based highly active antiretroviral therapy
      (HAART) regimen increases cardiovascular disease and endothelial dysfunction.
      However, the mechanisms of PI-induced effects on endothelial cells (ECs) are not
      known. Furthermore, strategies to suppress these deleterious outcomes of PIs need
      to be developed. Insulin-induced PI3K/Akt signaling and endothelial nitric oxide
      (NO)-synthase (eNOS) phosphorylation regulates NO production by ECs that maintain
      vascular homeostasis. We evaluated whether nelfinavir (NEL), a potent HIV-1 PI
      that suppresses Akt phosphorylation, can alter insulin-induced NO production in
      human aortic endothelial cells (HAECs) and whether insulin sensitization of HAECs
      via the peroxisome proliferator-activated receptor-gamma agonists,
      thiazolidinediones, can ameliorate these side effects. METHODS: Real-time NO
      production in HAECs was monitored by fluorimetric dyes DAF-FM DA and DAF-2 DA.
      Immunodetection studies were used to determine the phosphorylation of Akt, eNOS,
      insulin receptor-beta (IR-beta), insulin receptor substrate-1 (IRS-1), and
      PI3K/p85alpha. Expression of eNOS messenger RNA was measured by reverse
      transcription polymerase chain reaction. RESULTS: In vitro exposure (72 hours) of
      HAECs to NEL (0.25-2 MUg/mL) decreased both basal (2.5-fold) and insulin-induced
      NO production (4- to 5-fold). NEL suppressed insulin-induced phosphorylation of
      both Akt and eNOS at serine residues 473 and 1177, respectively. NEL decreased
      tyrosine phosphorylation of IR-beta, IRS-1, and PI3K. Coexposure to troglitazone
      (TRO; 250 nM) ameliorated the suppressive effects of NEL on insulin signaling and
      NO production. Coexposure to TRO also increased eNOS expression in NEL-treated
      HAECs. CONCLUSION: Our findings indicate that treatment with potent insulin
      sensitizers may protect against PI-mediated endothelial dysfunction during long
      term HAART.

PMID- 23533050
TI  - Promotion of spinal cord axon regeneration by 3D nanofibrous core-sheath
      scaffolds.
AB  - Since spinal cord injury is a complicated problem, neural tissue repair, and
      regeneration strategies have received a great deal of attention. In this study, a
      three-dimensional (3D) nanofibrous core-sheath scaffold with nanorough sheath and
      aligned core were fabricated by a combined electrospinning method with water
      vortex and two-nozzle system. In vitro and in vivo biological tests were carried
      out on the poly(lactic-co-glycolic acid) (PLGA) scaffolds. The cell morphology
      and proliferation evaluation of nerve cells on 3D PLGA scaffolds were studied.
      Cells were properly orientated along the aligned fiber direction of the scaffold.
      In animal studies, adult rats received a complete lateral hemisection at the T9
      T10 level. Scaffolds were engrafted to bridge 3 mm defects of 10 adult rat spinal
      cords; 10 rats were used as controls. For 8 weeks, motor and sensory recovery by
      open field locomotor scale, narrow beam and tail flick tests were assessed.
      Locomotor and sensory scores of grafted animals were significantly better than
      the control group. Histological findings demonstrated that the scaffold supports
      the axonal regeneration of injured spinal cords and regenerating axons were seen
      to enter the graft and extend along its length.

PMID- 23533052
TI  - Assembly of a cyclo-tetrastibinotetraphosphonium tetracation by reductive
      elimination.

PMID- 23533051
TI  - Laboratory handling of epididymal and testicular spermatozoa: What can be done to
      improve sperm injections outcome.
AB  - Spermatozoa from azoospermic males can be retrieved from either the epididymis or
      the testis, depending on the type of azoospermia, using different surgical
      methods such as percutaneous epididymal sperm aspiration (PESA), testicular sperm
      aspiration (TESA), testicular sperm extraction (TESE), and microsurgical
      testicular sperm extraction (micro- TESE). After collecting the epididymal fluid
      or testicular tissue, laboratory techniques are used to remove contaminants,
      cellular debris, noxious microorganisms, and red blood cells. Processed
      spermatozoa may be used for intracytoplasmic sperm injection or eventually be
      cryopreserved. However, spermatozoa collected from either the epididymis or the
      testis are often compromised and more fragile than ejaculated ones. Therefore,
      sperm processing techniques should be used with great caution to avoid
      jeopardizing the sperm fertilizing potential in treatment cycles. In this review,
      we describe the current methods for processing surgically-retrieved specimens,
      either fresh or frozen- thawed, and provide the tips and pitfalls for
      facilitating the handling of such specimens. In addition, we present the
      available laboratory tools to aid in the identification of viable immotile
      spermatozoa to be used in conjunction with assisted reproductive techniques.
      Review of the literature was carried out using PubMed and Science Direct search
      engines.

PMID- 23533053
TI  - Isomerization and epimerization of the aspartyl tetrapeptide Ala-Phe-Asp-GlyOH at
      pH 10-A CE study.
AB  - Isomerization and enantiomerization of Asp in the tetrapeptide Ala-Phe-Asp-GlyOH
      are studied at pH 10 and 80 degrees C as well as 25 degrees C. CE-MS allowed the
      distinction between alpha-Asp and beta-Asp linkages in degradation products based
      on the ratio of the b and y fragment ions. Besides isomerization and
      enantiomerization of Asp, enantiomerization of Ala and Phe was also observed at
      both temperatures by chiral amino acid HPLC analysis using Marfey's reagent for
      derivatization. The rate of enantiomerization of the amino acids proceeded in the
      order Asp > Ala > Phe. The CE assay was validated with respect to linearity, LOQ,
      LOD, and precision and employed to characterize the time course of the
      degradation of the tetrapeptide upon incubation in borate buffer, pH 10.
      Isomerization to beta-Asp peptides was identified as the major degradation
      reaction. The configuration of Asp or Ala affected the half-life of the starting
      peptide to a minor extent but did not influence the distribution of the
      individual products under equilibrium conditions at 80 degrees C. Degradation at
      25 degrees C proceeded very slowly so that the equilibrium was not reached after
      245 days. 

PMID- 23533054
TI  - Tsunami-tendenko and morality in disasters.
AB  - Disaster planning challenges our morality. Everyday rules of action may need to
      be suspended during large-scale disasters in favour of maxims that that may make
      prudential or practical sense and may even be morally preferable but emotionally
      hard to accept, such as tsunami-tendenko. This maxim dictates that the individual
      not stay and help others but run and preserve his or her life instead. Tsunami
      tendenko became well known after the great East Japan earthquake on 11 March
      2011, when almost all the elementary and junior high school students in one city
      survived the tsunami because they acted on this maxim that had been taught for
      several years. While tsunami-tendenko has been praised, two criticisms of it
      merit careful consideration: one, that the maxim is selfish and immoral; and two,
      that it goes against the natural tendency to try to save others in dire need. In
      this paper, I will explain the concept of tsunami-tendenko and then respond to
      these criticisms. Such ethical analysis is essential for dispelling confusion and
      doubts about evacuation policies in a disaster. 

PMID- 23533055
TI  - Live liver donation, ethics and practitioners: 'I am between the two and if I do
      not feel comfortable about this situation, I cannot proceed'.
AB  - This paper discusses the views of 17 healthcare practitioners involved with
      transplantation on the ethics of live liver donations (LLDs). Donations between
      emotionally related donor and recipients (especially from parents to their
      children) increased the acceptability of an LLD compared with those between
      strangers. Most healthcare professionals (HCPs) disapproved of altruistic
      stranger donations, considering them to entail an unacceptable degree of risk
      taking. Participants tended to emphasise the need to balance the harms of
      proceeding against those of not proceeding, rather than calculating the harm-to
      benefits ratio of donor versus recipient. Participants' views suggested that a
      complex process of negotiation is required, which respects the autonomy of donor,
      recipient and HCP. Although they considered that, of the three, donor autonomy is
      of primary importance, they also placed considerable weight on their own
      autonomy. Our participants suggest that their opinions about acceptable risk
      taking were more objective than those of the recipient or donor and were
      therefore given greater weight. However, it was clear that more subjective values
      were also influential. Processes used in live kidney donation (LKD) were thought
      to be a good model for LLD, but our participants stressed that there is a danger
      that patients may underestimate the risks involved in LLD if it is too closely
      associated with LKD.

PMID- 23533056
TI  - Acute renal failure associated with diphosphonic acid (HEDP): a case report.
AB  - A 26-year-old man with no significant past medical history presented to emergency
      department 1 hr after ingesting approximately 200 ml of HEDP 2010
      organophosphoric acid corrosion inhibitor. He had normal vital signs, physical
      examination and biochemical parameters. After 24 hr, he developed nausea with a
      decreased urine output. While his blood urea nitrogen, creatinine and uric acid
      levels increased to 36 mg/dl, 3.87 mg/dl, and 8.4 mg/dl, respectively; his serum
      calcium and phosphorus levels decreased to 7.4 mg/dl and 1.4 mg/dl, respectively.
      He had proteinuria, glucosuria, leukocyturia and high phosphorus excretion in the
      urine. On ultrasonographic examination, the kidneys were slightly enlarged and
      edematous. On the third day of hospitalization, creatinine level increased to
      8.81 mg/dl and metabolic acidosis developed. He underwent to hemodialysis therapy
      and renal functions improved uneventfully. CONCLUSION: This case represents an
      example of acute renal failure developed and recovering uneventfully after
      unintentionally ingestion of a bisphosphonate used in industry.

PMID- 23533057
TI  - [72-year-old patient with dark spot on the back after sun exposure].

PMID- 23533058
TI  - Overlap and specificity of genetic and environmental influences on excessive
      acquisition and difficulties discarding possessions: Implications for hoarding
      disorder.
AB  - A reluctance to discard items, leading to severely cluttered living spaces, is
      the landmark feature of hoarding disorder (HD). Many, but not all, individuals
      with HD also excessively acquire, buy or even steal items that they do not need
      and for which no space is available. In DSM-5, "excessive acquisition" can be
      coded as a specifier of HD. Despite their consistent co-occurrence, the question
      of whether excessive acquisition and difficulties discarding possessions share a
      common etiology remains unanswered. The current study sought to flesh out this
      relationship by examining the extent of shared genetic and environmental
      influences on the association between excessive acquisition and difficulties
      discarding in a community sample of adult, female twins. A total of 5,022 female
      twins (2,529 pairs; mean age = 55.5 years) completed a self-report measure of
      hoarding symptoms, including items assessing excessive acquisition and
      difficulties discarding. The data were analyzed using bivariate twin modeling
      methods in the statistical program Mx. As expected, we found a strong phenotypic
      correlation (0.63) between excessive acquisition and difficulty discarding items.
      Both traits were moderately heritable. The genetic correlation between the traits
      was estimated to be 0.77 (95% CI: 0.69-0.85), indicating a substantial but
      imperfect genetic overlap. The non-shared environmental correlation (0.50 [95%
      CI: 0.42-0.57]), though lower, was also significant. The findings demonstrate a
      substantial genetic, and more modest environmental, etiological overlap between
      the excessive acquisition of possessions and difficulties discarding them,
      providing a possible explanation for their frequent co-occurrence in HD. However,
      given that the etiological overlap is not perfect, unique etiological influences,
      particularly environmental, on each phenotype seem plausible.

PMID- 23533059
TI  - Different molecular weight hyaluronic acid effects on human macrophage
      interleukin 1beta production.
AB  - This study examined the effect of hyaluronan (HA) molecular weight on immune
      response. HA with molecular weights ranging from the unitary disaccharide unit
      (400 Da) up to 1.7 * 10(6) Da and with very low endotoxin contamination level
      (less than 0.03 EU/mg) was used. Primary human monocyte/macrophage cultures were
      assayed for IL-1beta production under a variety of inflammatory conditions with
      or without HA. Under the highest inflammatory states, production of interleukin
      1beta (IL-1beta) was suppressed in the presence of high molecular weight
      hyaluronan (HMW-HA) and in the presence of low molecular weight hyaluronan (LMW
      HA) at mg/mL concentrations. There was variability in the sensitivity of the
      response to HA fragments with MW below 5000 Da at micromolar concentrations.
      There was variability in IL-1beta cytokine productions from donor to donor in
      unstimulated human cell cultures. This study supplements our previous published
      study that investigated the immunogenic effect of HA molecular weights using
      murine cell line RAW264.6, rat splenocytes, and rat adherent differentiated
      primary macrophages. These data support the hypothesis that if the amount of
      endotoxin is reduced to an extremely low level, LMW-HA may not directly provoke
      normal tissue macrophage-mediated inflammatory reactions.

PMID- 23533060
TI  - Protoporphyrin IX fluorescence and photobleaching during interstitial
      photodynamic therapy of malignant gliomas for early treatment prognosis.
AB  - BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy (iPDT) of non
      resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced
      protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear,
      however, to what extent inter- and intra-tumoural differences of PpIX
      concentrations influence the efficacy of iPDT. In the current pilot study, we
      analysed PpIX concentrations quantitatively and assessed PpIX induced
      fluorescence and photobleaching intraoperatively. MATERIALS AND METHODS: Five
      patients harbouring non-resectable glioblastomas were included. ALA (20 or 30
      mg/kg body weight) was given 5-8 hours before treatment. Stereotactic biopsies
      were taken throughout the tumour volume for both histological analysis and
      determination of PpIX concentrations, which were measured by chemical extraction.
      Cylindrical light diffusors were stereotactically implanted. Prior to and after
      irradiation, fluorescence measurements were performed. Outcome measurement was
      based on clinical and neuro-radiological follow up. RESULTS: In three patients, a
      strong PpIX fluorescence was seen before treatment, which was completely
      photobleached after iPDT. High concentrations of PpIX could be detected in viable
      tumour parts of these patients (mean PpIX uptake per tumour: 1.4-3.0 uM). In the
      other two patients, however, no or only low PpIX uptake (0-0.6 uM) could be
      detected. The patients with strong PpIX uptake showed treatment response and long
      term clinical stabilisation (no progression in 29, 30 and 36 months), early
      treatment failure was seen in the remaining two patients (death after 3 and 9
      months). CONCLUSIONS: Intra-tumoural PpIX concentrations exhibited pronounced
      inter- and intra-tumoural variations in glioblastoma, which are directly linked
      to variable degrees of fluorescence intensity. High intra-tumoural PpIX
      concentrations with strong fluorescence intensity and complete photobleaching
      after iPDT seem to be associated with favourable outcome. Real-time monitoring of
      PpIX fluorescence intensity and photobleaching turned out to be feasible and safe
      and might be employed for early treatment prognosis of iPDT.

PMID- 23533061
TI  - Development of cortical bone geometry in the human femoral and tibial diaphysis.
AB  - Ontogenetic growth processes in human long bones are key elements, determining
      the variability of adult bone structure. This study seeks to identify and
      describe the interaction between ontogenetic growth periods and changes in
      femoral and tibial diaphyseal shape. Femora and tibiae (n = 46) ranging
      developmentally from neonate to skeletally mature were obtained from the Norris
      Farms No. 36 archeological skeletal series. High-resolution X-ray computed
      tomography scans were collected. Whole-diaphysis cortical bone drift patterns and
      relative bone envelope modeling activity across ages were assessed in five cross
      sections per bone (total bone length: 20%, 35%, 50%, 65%, and 80%) by measuring
      the distance from the section centroid to the endosteal and periosteal margins in
      eight sectors using ImageJ. Pearson correlations were performed to document and
      interpret the relationship between the cross-sectional shape (Imax /Imin ), total
      subperiosteal area, cortical area, and medullary cavity area for each slice
      location and age for both the femur and the tibia. Differences in cross-sectional
      shape between age groups at each cross-sectional position were assessed using
      nonparametric Mann-Whitney U tests. The data reveal that the femoral and tibial
      midshaft shape are relatively conserved throughout growth; yet, conversely, the
      proximal and distal femoral diaphysis and proximal tibial diaphysis appear more
      sensitive to developmentally induced changes in mechanical loading. Two time
      periods of accelerated change are identified: early childhood and
      prepuberty/adolescence.

PMID- 23533062
TI  - Survey of attitudes on professionalism in plastic and reconstructive surgery.
AB  - BACKGROUND: The purpose of this study is to analyze the current attitudes toward
      professionalism, the core values, and the type of professionalism among plastic
      surgeons in Korea to establish a code of ethics regarding the role of
      professionalism for plastic and reconstructive surgeons. METHODS: From March 9,
      to July 1, 2012, face-to-face and mail surveys were conducted targeting the 325
      participants (256 specialists and 69 residents) who are registered members of the
      Korean Society of Plastic and Reconstructive Surgeons. The proportion of each
      response given to an item was obtained through statistical processing through
      frequency analysis. The Mann-Whitney U test was used to compare the differences
      in the responses between the resident group and the specialist group. RESULTS:
      The survey results on the perception of professionalism in plastic surgery showed
      that a high proportion (90.5%) of the respondents viewed the future of plastic
      surgeons as bright. Through evaluation of the importance of the value
      items,"professional dominance" (4.58 pts), "autonomy" (4.45 pts), "lifestyle"
      (4.34 pts), and "commercialism" (4.31 pts) were assessed as critical values.
      "Altruism" (3.84 pts), "interpersonal competence" (3.79 pts), and "social
      justice" (3.61 pts) were viewed as lesser values. This difference showed the
      characteristics of an entrepreneurial outlook. CONCLUSIONS: Plastic surgeons
      should pursue excellence, humanism, accountability, and altruism in order to
      overcome the crisis of professionalism in plastic surgery. In order to develop
      the necessary competencies of professionals, vocational education should be
      arranged by the Korean Society of Plastic Surgeons, and an appropriate code of
      ethics should be established.

PMID- 23533063
TI  - Continued Circulation of G12P[6] Rotaviruses Over 28 Months in Nepal: Successive
      Replacement of Predominant Strains.
AB  - Rotavirus A causes severe diarrhoea in infants and young children worldwide. The
      migration pattern (electropherotype) of the double-stranded RNA genome upon
      polyacrylamide gel electrophoresis has been used to define "strains" in molecular
      epidemiology. In temperate countries, distinct electropherotypes (strains) appear
      after the annual, off-seasonal interruption of rotavirus circulation. In Nepal,
      rotavirus circulated year-round and an uncommon genotype G12P[6] predominated and
      persisted, providing a unique opportunity to examine whether the same
      electropherotype (the same strain) persisted or new electropherotypes (new
      strains) emerged successively under the same G12P[6] predominance. A total of 147
      G12P[6] rotaviruses, collected from diarrhoeal children in Nepal between 2007 and
      2010, were classified into 15 distinct electropherotypes (strains). Of these,
      three electropherotypes (strains), LP1, LP24, and LP27, accounted for 10%, 32%
      and 38% of the G12P[6] rotaviruses, respectively. Each of the three major strains
      successively appeared, dominated, and disappeared. This study provided new
      evidence for the hypothesis that rotavirus constantly changes its strains to
      predominate in the local population even under conditions where a single genotype
      predominates and persists. Such dynamic strain replacement, the constant takeover
      of one predominant strain by another, fitter strain, is probably gives a
      competitive edge to the survival of rotavirus in nature.

PMID- 23533064
TI  - Left atrial diameter and albumin with renal outcomes in chronic kidney disease.
AB  - BACKGROUND AND AIM: Echocardiographic left atrial diameter (LAD) has been
      documented to be an independent predictor of adverse cardiovascular outcomes in
      various populations. An enlarged left atrium is frequently noted in chronic
      kidney disease (CKD). We examined the association between albumin and indexed LAD
      (indexed to height) and assessed whether the combination of indexed LAD and
      albumin was independently associated with renal outcomes in patients with CKD
      stages 3-5. METHODS: This longitudinal study enrolled 395 patients, who were
      classified into four groups according to median values of indexed LAD
      (LAD/height) and albumin. The change in renal function was measured by estimated
      glomerular filtration rate (eGFR) slope. Rapid renal progression was defined as
      eGFR slope less than -3 ml/min/1.73 m(2)/year. The renal end point was defined as
      commencement of dialysis. RESULTS: Albumin was significantly associated with
      indexed LAD (beta = -0.108, P = 0.024). During follow-up period, seventy-four
      patients started dialysis. After the multivariate analysis, the group with higher
      indexed LAD and lower albumin was independently associated with rapid renal
      progression (odds ratio, 7.979; 95% confidence interval [CI], 3.028 to 21.025)
      and progression to dialysis (hazard ratio, 2.352; 95% CI, 1.078 to 5.131).
      CONCLUSIONS: Our findings show that albumin is independently associated with
      indexed LAD and suggest that the combination of increased indexed LAD and
      hypoalbuminemia is independently associated with rapid renal progression and
      progression to dialysis in patients with CKD. Assessments of serum albumin and
      indexed LAD by echocardiography are useful for predicting the risk for adverse
      renal outcomes.

PMID- 23533065
TI  - Brain processing of pain in patients with unresponsive wakefulness syndrome.
AB  - By definition, patients with unresponsive wakefulness syndrome (UWS) do not
      experience pain, but it is still not completely understood how far their brain
      can process noxious stimuli. The few positron emission tomography studies that
      have examined pain processing did not yield a clear and consistent result. We
      performed an functional magnetic resonance imaging scan in 30 UWS patients of
      nontraumatic etiology and 15 age- and sex-matched healthy control participants
      (HC). In a block design, noxious electrical stimuli were presented at the
      patients' left index finger, alternating with a resting baseline condition.
      Sixteen of the UWS patients (53%) showed neural activation in at least one
      subsystem of the pain-processing network. More specifically, 15 UWS patients
      (50%) showed responses in the sensory-discriminative pain network, 30% in the
      affective pain network. The data indicate that some patients completely
      fulfilling the clinical UWS criteria have the neural substrates of noxious
      stimulation processing, which resemble that in control individuals. We therefore
      suppose that at least some of these patients can experience pain.

PMID- 23533066
TI  - p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic
      in vivo.
AB  - The increasing prevalence and social burden of subclinical anxiety in the western
      world represents a significant psychosocial and financial cost. Consumers are
      favouring a more natural and nonpharmacological approach for alleviating the
      effects of everyday stress and anxiety. The gamma-aminobutyric acid (GABA)
      receptor is the primary mediator of central inhibitory neurotransmission, and
      GABA-receptor agonists are well known to convey anxiolytic effects. Using an in
      vitro screening approach to identify naturally occurring phytochemical GABA
      agonists, we discovered the plant secondary metabolite p-coumaric acid to have
      significant GABAergic activity, an effect that could be blocked by co
      administration of the specific GABA-receptor antagonist, picrotoxin. Oral
      administration of p-coumaric acid to rodents induced a significant anxiolytic
      effect in vivo as measured using the elevated plus paradigm, in line with the
      effects of oral diazepam. Given that p-coumaric acid is reasonably well absorbed
      following oral consumption in man and is relatively nontoxic, it may be suitable
      for the formulation of a safe and effective anxiolytic functional food.

PMID- 23533067
TI  - Supramolecular thiophene nanosheets.

PMID- 23533069
TI  - Outcome of total hip arthroplasty as a salvage procedure for failed infected
      internal fixation of hip fractures.
AB  - BACKGROUND: Failed infected internal fixation produces significant pain and
      functional disability. In infected internal fixation of hip fractures with
      partial or complete head destruction, total hip arthroplasty (THA) can be
      technically challenging; however, it restores hip biomechanics. The present study
      is to evaluate the results and assess the complications of THA following failed
      infected internal fixation of these fractures. MATERIALS AND METHODS: A
      retrospective review of prospectively collected data in a tertiary healthcare
      center was performed of 20 consecutive patients of THA following failed infected
      internal fixation operated between September 2001 and November 2007. There were
      11 dynamic hip screw failures for intertrochanteric fractures, 6 failed
      osteotomies following transcervical fractures, and 3 failed screw fixations for
      transcervical fractures. RESULTS: The average age of the patients was 48.5 years
      (range 28-70 years) and the average followup period was 6.5 years (range 3.5-10.5
      years). An indigenously designed cement spacer was used in a majority of patients
      (n = 15). The custom-made antibiotic impregnated cement spacer was prepared on
      table, with the help of a K-nail bent at 130 degrees , long stem Austin Moore's
      prosthesis (n=1), Charnley's prosthesis (n=1), or bent Rush nail (n=1). The
      antibiotic mixed cement was coated over the hardware in its doughy phase and
      appropriately shaped using an asepto syringe or an indigenously prepared spacer
      template. Nineteen of the 20 patients underwent two-stage revision surgeries. The
      average Harris hip score improved from 35.3 preoperatively to 82.85
      postoperatively at the last followup. A significant difference was found (P <
      0.0001). None of the patients had recurrence of infection. CONCLUSIONS: The
      results were comparable to primary arthroplasty in femoral neck fractures. Thus,
      THA is a useful salvage procedure for failed infected internal fixation of hip
      fractures.

PMID- 23533068
TI  - The Regulation of IGF-1 Gene Transcription and Splicing during Development and
      Aging.
AB  - It is commonly known that the insulin-like growth factor-I gene contains six
      exons that can be differentially spliced to create multiple transcript variants.
      Further, there are two mutually exclusive leader exons each having multiple
      promoter sites that are variably used. The mature IGF-I protein derived from the
      multiplicity of transcripts does not differ suggesting a regulatory role for the
      various transcript isoforms. The variant forms possess different stabilities,
      binding partners, and activity indicating a pivotal role for the isoforms.
      Research has demonstrated differential expression of the IGF-I mRNA transcripts
      in response to steroids, growth hormone, and developmental cues. Many studies of
      different tissues have focused on assessing the presence, or putative action, of
      the transcript isoforms with little consideration of the transcriptional
      mechanisms that generate the variants or the translational use of the transcript
      isoforms. Control points for the latter include epigenetic regulation of splicing
      and promoter usage in response to development or injury, RNA binding proteins and
      microRNA effects on transcript stability, and preferential use of two leader
      exons by GH and other hormones. This review will detail the current knowledge of
      the mechanical, hormonal, and developmental stimuli regulating IGF-1 promoter
      usage and splicing machinery used to create the variants.

PMID- 23533070
TI  - Congenital malformations and assisted reproductive technique: Where is assisted
      reproductive technique taking us?
AB  - Development of ART has great benefit for millions of couples all over the world
      and with falling fertility rate there are a growing numbers of children born with
      the help of ART, it is important to investigate potential risks to these
      children. IVF-ICSI pregnancies are associated with higher risk for multiple
      gestation, preterm labor and low birth weight. It is an area of great conflict
      and interest that whether ART is associated with increased congenital
      malformations or not. So, this article reviews the data and evidences linking ART
      to congenital malformations.

PMID- 23533071
TI  - New support for an old hypothesis: density affects extra-pair paternity.
AB  - Density has been suggested to affect variation in extra-pair paternity (EPP) in
      avian mating systems, because increasing density promotes encounter rates and
      thus mating opportunities. However, the significance of density affecting EPP
      variation in intra- and interspecific comparisons has remained controversial,
      with more support from intraspecific comparisons. Neither experimental nor
      empirical studies have consistently provided support for the density hypothesis.
      Testing the density hypothesis is challenging because density measures may not
      necessarily reflect extra-pair mating opportunities, mate guarding efforts may
      covary with density, populations studied may differ in migratory behavior and/or
      climatic conditions, and variation in density may be insufficient. Accounting for
      these potentially confounding factors, we tested whether EPP rates within and
      among subpopulations of the reed bunting (Emberiza schoeniclus) were related to
      density. Our analyses were based on data from 13 subpopulations studied over 4
      years. Overall, 56.4% of totally 181 broods contained at least one extra-pair
      young (EPY) and 37.1% of totally 669 young were of extra-pair origin. Roughly 90%
      of the extra-pair fathers were from the adjacent territory or from the territory
      after the next one. Within subpopulations, the proportion of EPY in broods was
      positively related to local breeding density. Similarly, among subpopulations,
      proportion of EPY was positively associated with population density. EPP was
      absent in subpopulations consisting of single breeding pairs, that is, without
      extra-pair mating opportunities. Our study confirms that density is an important
      biological factor, which significantly influences the amount of EPP within and
      among subpopulations, but also suggests that other mechanisms influence EPP
      beyond the variation explained by density.

PMID- 23533072
TI  - Emergency management of acute obstructed left-sided colon cancer: loops, stents
      or tubes?

PMID- 23533073
TI  - Follow-up of premalignant lesions in patients at risk for progression to gastric
      cancer.
AB  - BACKGROUND AND STUDY AIMS: A recent international guideline recommends
      surveillance of premalignant gastric lesions for patients at risk of progression
      to gastric cancer. The aim of this study was to identify the role of the
      distribution and severity of premalignant lesions in risk categorization.
      PATIENTS AND METHODS: Patients with a previous diagnosis of atrophic gastritis,
      intestinal metaplasia, or low grade dysplasia were invited for surveillance
      endoscopy with non-targeted biopsy sampling. Biopsy specimens were evaluated by
      pathologists (four general and one expert) using the Sydney and the operative
      link for gastric intestinal metaplasia (OLGIM) systems, and scores were compared
      using kappa statistics. RESULTS: 140 patients were included. In 37 % (95 %
      confidence interval [CI] 29 % - 45 %) the severity of premalignant lesions was
      less than at baseline, while 6 % (95 %CI 2 % - 10 %) showed progression to more
      severe lesions. Intestinal metaplasia in the corpus was most likely to progress
      to more than one location (57 %; 95 %CI 36 % - 76 %). The proportion of patients
      with multilocated premalignant lesions increased from 24 % at baseline to 31 % at
      surveillance (P = 0.014). Intestinal metaplasia was the premalignant lesion most
      frequently identified in subsequent endoscopies. Intestinal metaplasia regressed
      in 27 % compared with 44 % for atrophic gastritis and 100 % for low grade
      dysplasia. Interobserver agreement was excellent for intestinal metaplasia (k =
      0.81), moderate for dysplasia (k = 0.42), and poor for atrophic gastritis (k <
      0). CONCLUSIONS: Premalignant gastric lesions found in the corpus have the
      highest risk of progression, especially intestinal metaplasia, which has
      excellent interobserver agreement. This supports the importance of intestinal
      metaplasia as marker for follow-up in patients with premalignant gastric lesions.

PMID- 23533074
TI  - Reflux and Barrett's disease: revival of endoscopic antireflux procedures?
AB  - After the initial enthusiasm at the end of the previous century, interest in
      endoscopic anti-reflux procedures decreased due to inefficiency or complications
      with devices, a lack of good clinical trials, or financial problems of the
      manufacturers. In 2012 some interesting results on new and old devices have been
      published.

PMID- 23533075
TI  - Upper gastrointestinal tumors.

PMID- 23533076
TI  - Colonoscopy, tumors.

PMID- 23533077
TI  - Preparation, sedation, and monitoring.

PMID- 23533078
TI  - Innovations and NOTES.

PMID- 23533079
TI  - PillCam Colon and ulcerative colitis: what do physicians need to know?

PMID- 23533081
TI  - Adenoviral insulinoma-associated protein 1 promoter-driven suicide gene therapy
      with enhanced selectivity for treatment of neuroendocrine cancers.
AB  - BACKGROUND: Insulinoma-associated protein 1 (INSM1) is a zinc finger
      transcriptional repressor with a limited spatial and temporal embryonic
      expression pattern in neuronal and neuroendocrine tissues. Interestingly, INSM1
      activity is reactivated in neuroendocrine tumors such as small-cell lung cancer
      (SCLC), neuroblastoma, medulloblastoma, and retinoblastoma. Adenoviral constructs
      with the 1.7-kilobase pair INSM1 promoter-driven herpes simplex virus thymidine
      kinase (HSV-tk) gene could effectively suppress D283 Med subcutaneous xenograft
      tumor growth. Undesirably, sequences in the adenoviral backbone overrode promoter
      specificity in vivo. Incorporation of both the chicken beta-globin HS4 insulator
      sequence and 2 copies of the mouse nicotinic acetylcholine receptor (nAchR)
      neuronal restrictive silencer element abolished the nonspecific activation of the
      INSM1 promoter in vivo. METHODS: The luciferase reporter gene was replaced with
      the HSV-tk suicide gene to generate the Ad-K5 virus. Both in vitro cell viability
      assays and in vivo tumor regression studies were used to determine the efficacy
      of the improved configuration INSM1 promoter adenoviral construct against a panel
      of neuroendocrine cell lines. RESULTS: In vitro cell viability assays with the Ad
      K5 HSV-tk-expressing construct further reinforced that the Ad-K5 virus could
      eradicate SCLC, insulinoma, medulloblastoma, and neuroblastoma cells. Further, Ad
      K5 virus treatment of a D283 Med subcutaneous xenograft tumor showed a superior
      antitumor effect over the control Ad-RSV (Rous sarcoma virus)-HSV-tk.
      CONCLUSIONS: Improvements to the INSM1 promoter resulted in a stronger and more
      selective adenovirus. Treatment of a panel of neuroendocrine carcinomas with the
      Ad-K5 virus revealed enhanced antitumor activity over the RSV control,
      demonstrating its usefulness for the treatment of a variety of neuroendocrine
      tumors.

PMID- 23533082
TI  - Kappa statistic for clustered dichotomous responses from physicians and patients.
AB  - The bootstrap method for estimating the standard error of the kappa statistic in
      the presence of clustered data is evaluated. Such data arise, for example, in
      assessing agreement between physicians and their patients regarding their
      understanding of the physician-patient interaction and discussions. We propose a
      computationally efficient procedure for generating correlated dichotomous
      responses for physicians and assigned patients for simulation studies. The
      simulation result demonstrates that the proposed bootstrap method produces better
      estimate of the standard error and better coverage performance compared with the
      asymptotic standard error estimate that ignores dependence among patients within
      physicians with at least a moderately large number of clusters. We present an
      example of an application to a coronary heart disease prevention study.

PMID- 23533083
TI  - Long-term down-regulation of GABA decreases orientation selectivity without
      affecting direction selectivity in mouse primary visual cortex.
AB  - Inhibitory interneurons play important roles in the development of brain
      functions. In the visual cortex, functional maturation of inhibitory interneurons
      is essential for ocular dominance plasticity. However, roles of inhibitory
      interneurons in the development of orientation and direction selectivity,
      fundamental properties of primary visual cortex, are less understood. We examined
      orientation and direction selectivity of neurons in GAD67-GFP (Deltaneo) mice, in
      which expression of GABA in the brain is decreased in the newborn. We used in
      vivo two-photon calcium imaging to examine visual response of neurons in these
      mice and found that long-term decrease of GABA led to increase of response
      amplitude to non-preferred orientation of visual stimuli, which decreased
      orientation selectivity. In contrast, direction selectivity was not affected.
      These results suggest that orientation selectivity is decreased in mice with GABA
      down-regulation during development.

PMID- 23533084
TI  - Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure
      to titanium dioxide nanoparticles.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) are widely used in toothpastes,
      sunscreens, and products for cosmetic purpose that the human use daily. Although
      the neurotoxicity induced by TiO2 NPs has been demonstrated, very little is known
      about the molecular mechanisms underlying the brain cognition and behavioral
      injury. In this study, mice were exposed to 2.5, 5, and 10 mg/kg body weight (BW)
      TiO2 NPs by nasal administration for 90 consecutive days, respectively, and their
      brains' injuries and brain gene-expressed profile were investigated. Our findings
      showed that TiO2 NPs could be translocated and accumulated in brain, led to
      oxidative stress, overproliferation of all glial cells, tissue necrosis as well
      as hippocampal cell apoptosis. Furthermore, microarray data showed significant
      alterations in the expression of 249 known function genes, including 113 genes
      upregulation and 136 genes downregulation following exposure to 10 mg/kg BW TiO2
      NPs, which were associated with oxidative stress, immune response, apoptosis,
      memory and learning, brain development, signal transduction, metabolic process,
      DNA repair, response to stimulus, and cellular process. Especially, significant
      increases in Col1a1, serine/threonine-protein kinase 1, Ctnnb1, cysteine-serine
      rich nuclear protein-1, Ddit4, Cyp2e1, and Krev interaction trapped protein 1
      (Krit1) expressions and great decreases in DA receptor D2, Neu1, Fc receptor-like
      molecules, and Dhcr7 expressions following long-term exposure to TiO2 NPs
      resulted in neurogenic disease states in mice. Therefore, these genes may be
      potential biomarkers of brain toxicity caused by TiO2 NPs exposure, and the
      application of TiO2 NPs should be carried out cautiously.

PMID- 23533085
TI  - Discordant results between fetal karyotyping and non-invasive prenatal testing by
      maternal plasma sequencing in a case of uniparental disomy 21 due to trisomic
      rescue.
AB  - Uniparental disomy (UPD) is an uncommon chromosome condition, but UPD involving
      chromosome 21 is rarely reported. We reported here a case who had first trimester
      screening test for Down syndrome, chorionic villus sampling for fetal
      karyotyping, quantitative fluorescence polymerase chain reaction (QF-PCR), as
      well as non-invasive prenatal testing (NIPT) by maternal plasma sequencing. There
      were discordant results between fetal karyotyping and NIPT due to UPD 21combined
      with confined placental mosaicism of trisomy 21. This demonstrated that it is
      possible to detect placental mosaicism by NIPT, but further studies are required
      to confirm its sensitivity. Therefore, all positive NIPT results must be
      confirmed by conventional invasive test and karyotyping. QF-PCR has the
      additional benefit in diagnosing UPD.

PMID- 23533087
TI  - The translucent cadaver: a follow-up study to gauge the efficacy of implementing
      changes suggested by students.
AB  - In a study conducted in 2011, the use of full body digital X-ray images
      (Lodox((r)) Statscan((r))) and drawings were described for surface anatomy
      education during which suggestions were made by students on how to improve the
      method. Educational innovations should continuously be adjusted and improved to
      provide the best possible scenario for student learning. This study, therefore,
      reports on the efficacy of implementing some of these suggestions. Suggestions
      incorporated into the follow-up study included: (1) The inclusion of eight
      strategically placed labeled digital X-ray images to the dissection halls, (2)
      The placement of both labeled and unlabeled digital X-ray images online, (3) The
      inclusion of informal oral questions on surface anatomy during dissection, (4)
      The requirement of students to submit individual drawings in addition to group
      drawings into their portfolios, and (5) Integrating information on how to
      recognize anatomical structures on X-rays into gross anatomy lectures given prior
      to dissection. Students were requested to complete an anonymous questionnaire.
      The results of the drawings, tests and questionnaires were compared to the
      results from the 2011 cohort. During 2012, an increased usage of the digital X
      rays and an increase in practical test marks in three out of the four modules
      (statistically significant only in the cardiovascular module) were reported. More
      students from the 2012 cohort believed the images enhanced their experience of
      learning surface anatomy and that its use should be continued in future. The
      suggested changes, therefore, had a positive effect on surface anatomy education.

PMID- 23533086
TI  - Quantitative proteomics of tomato defense against Pseudomonas syringae infection.
AB  - Genetic and microarray analyses have provided useful information in the area of
      plant and pathogen interactions. Pseudomonas syringae pv. tomato DC3000 (Pst)
      causes bacterial speck disease in tomato. Previous studies have shown that
      changes in response to pathogen infection at transcript level are variable at
      different time points. This study provides information not only on proteomic
      changes between a resistant and a susceptible genotype, but also information on
      changes between an early and a late time point. Using the iTRAQ quantitative
      proteomics approach, we have identified 2369 proteins in tomato leaves, and 477
      of them were determined to be responsive to Pst inoculation. Unique and
      differential proteins after each comparison were further analyzed to provide
      information about protein changes and the potential functions they play in the
      pathogen response. This information is applicable not only to tomato proteomics,
      but also adds to the repertoire of proteins now available for crop proteomic
      analysis and how they change in response to pathogen infection. 

PMID- 23533088
TI  - Investigation of field and diffusion time dependence of the diffusion-weighted
      signal at ultrahigh magnetic fields.
AB  - Over the last decade, there has been a significant increase in the number of high
      magnetic-field MRI magnets. However, the exact effect of a high magnetic field
      strength (B0 ) on diffusion-weighted MR signals is not yet fully understood. The
      goal of this study was to investigate the influence of different high magnetic
      field strengths (9.4 T and 14.1 T) and diffusion times (9, 11, 13, 15, 17 and 24
      ms) on the diffusion-weighted signal in rat brain white matter. At a short
      diffusion time (9 ms), fractional anisotropy values were found to be lower at
      14.1 T than at 9.4 T, but this difference disappeared at longer diffusion times.
      A simple two-pool model was used to explain these findings. The model describes
      the white matter as a first hindered compartment (often associated with the extra
      axonal space), characterized by a faster orthogonal diffusion and a lower
      fractional anisotropy, and a second restricted compartment (often associated with
      the intra-axonal space), characterized by a slower orthogonal diffusion (i.e.
      orthogonal to the axon direction) and a higher fractional anisotropy. Apparent T2
      relaxation time measurements of the hindered and restricted pools were performed.
      The shortening of the pseudo-T2 value from the restricted compartment with B0 is
      likely to be more pronounced than the apparent T2 changes in the hindered
      compartment. This study suggests that the observed differences in diffusion
      tensor imaging parameters between the two magnetic field strengths at short
      diffusion time may be related to differences in the apparent T2 values between
      the pools.

PMID- 23533089
TI  - A chemical probe for lysine malonylation.

PMID- 23533090
TI  - Tailoring properties of microsphere-based poly(lactic-co-glycolic acid)
      scaffolds.
AB  - Biodegradable polymer scaffolds are being extensively investigated for uses in
      tissue engineering because of their versatility in fabrication methods and range
      of achievable chemical and mechanical properties. In this study, poly(lactic-co
      glycolic acid) (PLGA) was used to make various types of microspheres that were
      processed into porous scaffolds that possessed a wide range of properties. A heat
      sintering step was used to fuse microspheres together around porogen particles
      that were subsequently leached out, allowing for a 10-fold increase in mechanical
      properties over other PLGA scaffolds. The sintering temperature was based on the
      glass transition temperature that ranged from 43 to 49 degrees C, which was low
      enough to enable drug loading. Degradation times were observed to be between 30
      and 120 days, with an initial compressive modulus ranging from 10 to 100 MPa, and
      after 5 days of degradation up to 10 MPa was retained. These scaffolds were
      designed to allow for cell ingrowth, enable drug loading, and have an adjustable
      compressive modulus to be applicable for soft or hard tissue implants. This study
      combined well-established methods, such as double emulsion microspheres, polymer
      sintering, and salt leaching, to fabricate polymer scaffolds useful for different
      tissue engineering applications.

PMID- 23533091
TI  - Estimating parsimonious models of longitudinal causal effects using regressions
      on propensity scores.
AB  - Parsimony is important for the interpretation of causal effect estimates of
      longitudinal treatments on subsequent outcomes. One method for parsimonious
      estimates fits marginal structural models by using inverse propensity scores as
      weights. This method leads to generally large variability that is uncommon in
      more likelihood-based approaches. A more recent method fits these models by using
      simulations from a fitted g-computation, but requires the modeling of high
      dimensional longitudinal relations that are highly susceptible to
      misspecification. We propose a new method that, first, uses longitudinal
      propensity scores as regressors to reduce the dimension of the problem and then
      uses the approximate likelihood for the first estimates to fit parsimonious
      models. We demonstrate the methods by estimating the effect of anticoagulant
      therapy on survival for cancer and non-cancer patients who have inferior vena
      cava filters.

PMID- 23533092
TI  - What would surgeons like from materials scientists?
AB  - Surgery involves the repair, resection, replacement, or improvement of body parts
      and functions and in numerous ways, surgery should be considered human
      engineering. There are many areas in which surgical materials could be improved,
      but surgeons are generally unaware of materials available for use, while
      materials scientists do not know what surgeons require. This article will review
      some of the areas where surgeons and materials scientists have interacted in the
      past and will discuss some of the most pressing problems which remain to be
      solved. These include better implant materials for hernia repair, breast
      reconstruction, the treatment of diabetes, vascular stenting and reconstruction,
      and electrical pacing devices. The combination of tissue engineering and
      nanomaterials has great potential for application to nearly every aspect of
      surgery. Tissue engineering will allow cells or artificial organs to be grown for
      specific uses while nanotechnology will help to ensure maximal biocompatibility.
      Biosensors will be combined with improved electrodes and pacing devices to
      control impaired neurological functions.

PMID- 23533093
TI  - [Adjusting for patient characteristics when evaluating questionnaire data].
AB  - INTRODUCTION: Patient questionnaires are a frequently used instrument within the
      framework of quality management in in- and outpatient care. Often such
      questionnaires enable a comparison of care suppliers with the consequence that
      one turns out to be visibly better or poorer than another. This process, in turn,
      makes it necessary to check whether differences found upon evaluation of the
      questionnaires are not merely the result of different compositions of the
      questioned populations. Although frequently demanded, such adjustments are not
      usually made. The present article describes the choice of variables for
      adjustments and the statistical procedures for a relatively homogeneous sample of
      breast cancer patients. In addition, the utility and limitations of adjustments
      are discussed. METHODS: On the basis of questionnaire data from 3 840 breast
      cancer patients of 52 breast cancer centres in North Rhine-Westphalia collected
      during 2010, we examined which patient characteristics can be employed for the
      adjustment of satisfaction ratings and to what extent the observed values for the
      centres differed from the expected results. Independent variables taken into
      consideration were age, educational level, native language, stage, grading, ASA
      classification, afffected breast, type of operation, insurance status,
      partnership status as well as time between operation and receipt of the filled
      out questionnaire. RESULTS: The variance revealed by the independent variables is
      low. The expected values showed minimal differences which can be attributed to
      the high homogeneity of the patients collectives and the centres. CONCLUSION: The
      use of adjustments remains limited in the study population. The variance of the
      independent variables revealed by the adjustors is small. Finally, in our
      opinion, no clear recommmendation for or against case-mix adjustments can be made
      in patient populations such as the one examined here. Thus, even when small,
      effects for a more correct reporting of patient questionnaires are faced with
      unresolvable methodological challenges. Also of importance but an as yet only
      rarely discussed factor is the factual intepretation of the association of
      patient characteristics with a better or poorer evaluation of questionnaires. An
      adjustment for the respective characteristics would eliminate these findings and
      not make any contribution to an improvement in health care.

PMID- 23533095
TI  - Women and their partners' preferences for Down's syndrome screening tests: a
      discrete choice experiment.
AB  - OBJECTIVES: This study aimed to determine quantitatively the attributes of such
      screening tests that couples placed most value on. METHODS: A stated preference
      discrete choice experiment was conducted among a sample of pregnant women and
      their male partners. One four-level attribute (cost) and three two-level
      attributes (detection rate, gestation and time to wait for results) were used to
      generate eight hypothetical pairs of tests. RESULTS: A total of 103 participants
      fully completed the questionnaire (63 women, 40 men). Overall, the sample was
      most concerned with test cost. However, latent class analysis showed three groups
      of participants whose concern for attributes differed, with cost, detection rate
      and delay in receiving results being the most important to each. Willingness to
      pay calculations showed that participants who were most concerned with detection
      rate were prepared to pay more than four times the amount than those most cost
      sensitive would pay for the 'best test' option as compared with the 'worst test'.
      CONCLUSIONS: Overall, couples were sensitive to the price of the screening test,
      but explicit subgroups are also shown that would pay large amounts for
      improvements in other attributes, particularly detection rates. This could
      provide important information to policymakers and practitioners in antenatal
      care, specifically in relation to the trade-offs made when couples decide about
      antenatal screening tests.

PMID- 23533094
TI  - Identification of host proteins modulated by the virulence factor AC2 of Tomato
      chlorotic mottle virus in Nicotiana benthamiana.
AB  - Tomato, one of the most important crops cultivated worldwide, has been severely
      affected by begomoviruses such as the Tomato chlorotic mottle virus (ToCMoV).
      Virulence factor AC2 is considered crucial for a successful virus-plant
      interaction and is known to act as a transcriptional activator and in some
      begomoviruses to function as an RNA silencing suppressor factor. However, the
      exact functions of the AC2 protein of the begomovirus ToCMoV are not yet
      established. The aim of the present study was to identify differentially
      expressed proteins of the model plant Nicotiana benthamiana in response to the
      expression of the AC2 gene, isolated from ToCMoV. N. benthamiana plants were
      inoculated with Agrobacterium tumefaciens containing the viral vector Potato
      virus X (PVX) and with the PVX-AC2 construction. 2DE was performed and proteins
      were identified by MS. The results showed that the expression of ToCMoV AC2
      alters the levels of several host proteins, which are important for normal plant
      development, causing an imbalance in cellular homeostasis. This study highlights
      the effect of AC2 in the modulation of plant defense processes by increasing the
      expression of several oxidative stress-related and pathogenesis-related proteins,
      as well as its role in modulating the proteome of the photosynthesis and energy
      production systems. 

PMID- 23533096
TI  - Comparison of angiogenic potential between prevascular and non-prevascular
      layered adipose-derived stem cell-sheets in early post-transplanted period.
AB  - Layered adipose-derived stem cell (ADSC) sheet transplantation is attracting
      attention as a new stem cell therapeutic strategy for damaged hearts. To prolong
      the function of tissue-engineered constructs after transplantation, a rapid and
      sufficient vascularization of engrafted tissue is essential. The in vitro
      formation of network structures derived from endothelial cells (ECs) in grafts
      before transplantation contributes to the induction of functional anastomosis in
      vivo. This study compared the angiogenic potential of ADSC sheets containing
      dissociated ECs (non-prevascular cell-sheets) and networked ECs (prevascular cell
      sheets) after transplantation. For preparing the two different types of ECs
      containing layered cell-sheets, human umbilical vein endothelial cells (HUVECs)
      were sandwiched between two human ADSC sheets. Non-prevascular cell-sheets were
      obtained immediately after sandwiching without further cultivation. Prevascular
      cell-sheets were harvested form temperature-responsive culture dishes following
      re-cultivation for allowing them to form an EC network structure. In transplant
      experiments in the subcutaneous tissues of immune-deficient rat for 4 days,
      prevascular cell-sheets were observed to promote neovascularization with HUVEC
      lined microvessels. In contrast, neovessels were hardly observed in non
      prevascular cell-sheets. These results suggested that prefabricated EC network in
      layered cell-sheet was effective for making a rapid connection to the host
      vasculature in the early post-transplanted period.

PMID- 23533097
TI  - Progesterone supplementation in women with otherwise unexplained recurrent
      miscarriages.
AB  - CONTEXT: Recurrent miscarriages, the loss of three or more consecutive
      intrauterine pregnancies before 20 weeks of gestation with the same partner,
      affect 1%-1.5% of the pregnant population. The inadequate secretion of
      progesterone in early pregnancy has been proposed as a cause of recurrent
      miscarriages. AIMS: The aim was to investigate the efficacy of progesterone
      supplementation in patients with unexplained recurrent miscarriages. SETTINGS AND
      DESIGN: This was a 9-year cohort study of women with otherwise unexplained
      recurrent miscarriages who attended a recurrent miscarriage clinic in a tertiary
      care university hospital. SUBJECTS AND METHODS: Women with at least three
      unexplained recurrent miscarriages were included in the study. They were divided
      into three groups according to their initial and 48-h repeat progesterone levels.
      For women with inadequate endogenous progesterone secretion, natural progesterone
      vaginal pessaries 400 mg 12-hourly were offered until 12 weeks gestation.
      STATISTICAL ANALYSIS: Proportions and 95% confidence intervals calculated for
      categorical variables and the chi-square test were used to show statistical
      significance. Medians and ranges were calculated for noncontinuous variables.
      RESULTS: Pregnancy cycles (n = 203) were analyzed to examine the miscarriage rate
      following progesterone supplementation. Overall live birth and miscarriage rates
      were 63% and 36%, respectively. When analyzed by the number of previous
      miscarriages there was a reduction in the miscarriage rate following progesterone
      supplementation in women with 4 previous miscarriages when compared with
      historical data. CONCLUSIONS: Progesterone supplementation may have beneficial
      effects in women with otherwise unexplained recurrent miscarriages.

PMID- 23533098
TI  - Respiratory and behavioral dysfunction following loss of the GABAA receptor
      alpha4 subunit.
AB  - gamma-Aminobutyric acid type A (GABAA) receptor plasticity participates in
      mediating adaptation to environmental change. Previous studies in rats
      demonstrated that extrasynaptic GABAA receptor subunits and receptors in the
      pons, a brainstem region involved in respiratory control, are upregulated by
      exposure to sustained hypobaric hypoxia. In these animals, expression of the mRNA
      encoding the extrasynaptic alpha4 subunit rose after 3 days in sustained hypoxia,
      while those encoding the alpha6 and delta subunits increased dramatically by 2
      weeks. However, the participation of extrasynaptic subunits in maintaining
      respiration in normoxic conditions remains unknown. To examine the importance of
      alpha4 in a normal environment, respiratory function, motor and anxiety-like
      behaviors, and expression of other GABAA receptor subunit mRNAs were compared in
      wild-type (WT) and alpha4 subunit-deficient mice. Loss of the alpha4 subunit did
      not impact frequency, but did lead to reduced ventilatory pattern variability. In
      addition, mice lacking the subunit exhibited increased anxiety-like behavior.
      Finally, alpha4 subunit loss resulted in reduced expression of other
      extrasynaptic (alpha6 and delta) subunit mRNAs in the pons without altering those
      encoding the most prominent synaptic subunits. These findings on subunit
      deficient mice maintained in normoxia, in conjunction with earlier findings on
      animals maintained in chronic hypoxia, suggest that the expression and regulation
      of extrasynaptic GABAA receptor subunits in the pons is interdependent and that
      their levels influence respiratory control as well as adaptation to stress.

PMID- 23533099
TI  - Lipid goal attainment and prescription behavior in asian patients with acute
      coronary syndromes: experience from a tertiary hospital.
AB  - Lipid goal attainment studies in Asian patients with acute coronary syndrome
      (ACS) are limited. The objectives of this study were to determine low-density
      lipoprotein cholesterol (LDL-C) goal attainment rate at 4 months, and to examine
      prescription behavior influencing lipid goal attainment in Asian patients with
      ACS. A retrospective analysis of 267 patients with ACS was performed. The mean
      follow-up duration was 41.2+/-10.7 months. LDL-C goal attainment rate was highest
      at 4 months (36.7%) but declined progressively throughout follow-up. More than
      85% of patients were discharged with equipotent statin dose of 2 (equivalent to
      simvastatin 20 mg) or less. In patients who did not attain LDL-C goals, the
      statin dose remained low throughout follow-up because of a lack in responsive
      dose titration. Aggressive lipid-lowering therapy should be initiated early to
      improve goal attainment in these high-risk patients.

PMID- 23533100
TI  - Neuroplasticity-based cognitive and linguistic skills training improves reading
      and writing skills in college students.
AB  - This study reports an evaluation of the effect of computer-based cognitive and
      linguistic training on college students' reading and writing skills. The computer
      based training included a series of increasingly challenging software programs
      that were designed to strengthen students' foundational cognitive skills (memory,
      attention span, processing speed, and sequencing) in the context of listening and
      higher level reading tasks. Twenty-five college students (12 native English
      language; 13 English Second Language), who demonstrated poor writing skills,
      participated in the training group. The training group received daily training
      during the spring semester (11 weeks) with the Fast ForWord Literacy (FFW-L) and
      upper levels of the Fast ForWord Reading series (Levels 3-5). The comparison
      group (n = 28) selected from the general college population did not receive
      training. Both the training and comparison groups attended the same university.
      All students took the Gates MacGinitie Reading Test (GMRT) and the Oral and
      Written Language Scales (OWLS) Written Expression Scale at the beginning (Time 1)
      and end (Time 2) of the spring college semester. Results from this study showed
      that the training group made a statistically greater improvement from Time 1 to
      Time 2 in both their reading skills and their writing skills than the comparison
      group. The group who received training began with statistically lower writing
      skills before training, but exceeded the writing skills of the comparison group
      after training.

PMID- 23533101
TI  - First successful case of non-invasive in-utero treatment of twin reversed
      arterial perfusion sequence by high-intensity focused ultrasound.
AB  - High-intensity focused ultrasound (HIFU) has excellent potential as a non
      invasive therapeutic tool in various fields of medicine. We present a case of
      twin reversed arterial perfusion sequence, in which non-invasive blood flow
      occlusion in the acardiac fetus was successfully achieved by means of HIFU
      exposure from outside the maternal abdomen. HIFU was applied to blood vessels of
      the acardiac fetus at the point at which the umbilical cord entered the body in a
      series of four procedures at 3-day intervals starting at 13 weeks' gestation, and
      in a final procedure with higher power at 17 weeks. The HIFU intensity was set at
      approximately 2300 W/cm(2) for the initial series of procedures and at 4600
      W/cm(2) for the final procedure, with exposure periods of 10 s. As color Doppler
      examination revealed absence of blood flow to the acardiac fetus after the second
      round of HIFU exposure, we concluded that complete occlusion of target vessels
      had been achieved. Delivery was by Cesarean section at 37 weeks' gestation. A
      male neonate (the pump fetus) was born weighing 1903 g with Apgar scores of 8 and
      9 at 1 and 5 min, respectively. At the time of writing, the baby was healthy and
      growing normally, with the exception of congenital pseudarthrosis.

PMID- 23533103
TI  - Adipofascial anterolateral thigh flap safety: applications and complications.
AB  - BACKGROUND: A thinned anterolateral thigh (ALT) flap is often harvested to
      achieve optimal skin resurfacing. Several techniques have been described to thin
      an ALT flap including an adipocutaneous flap, an adipofascial flap and delayed
      debulking. METHODS: By systematically reviewing all of the available literature
      in English and French, the present manuscript attempts to identify the common
      surgical indications, complications and donor site morbidity of the adipofascial
      variant of the ALT flap. The studies were identified by performing a systematic
      search on Medline, Ovid, EMBASE, the Cochrane Database of Systematic Reviews,
      Current Contents, PubMed, Google, and Google Scholar. RESULTS: The study
      selection process was adapted from the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses statement, and 15 articles were identified using the
      study inclusion criteria. These articles were then reviewed for author name(s),
      year of publication, flap dimensions and thickness following defatting,
      perforator type, type of transfer, complications, thinning technique, number of
      cases with a particular area of application and donor site morbidity.
      CONCLUSIONS: The adipofascial variant of the ALT flap provides tissue to fill
      large defects and improve pliability. Its strong and safe blood supply permits
      adequate immediate or delayed debulking without vascular complications. The
      presence of the deep fascia makes it possible to prevent sagging by suspending
      and fixing the flap for functional reconstructive purposes (e.g., the intraoral
      cavity). Donor site morbidity is minimal, and thigh deformities can be reduced
      through immediate direct closure or liposuction and direct closure. A safe blood
      supply was confirmed by the rate of secondary flap debulking.

PMID- 23533102
TI  - Comparing constitutive and induced costs of symbiont-conferred resistance to
      parasitoids in aphids.
AB  - Host defenses against parasites do not come for free. The evolution of increased
      resistance can be constrained by constitutive costs associated with possessing
      defense mechanisms, and by induced costs of deploying them. These two types of
      costs are typically considered with respect to resistance as a genetically
      determined trait, but they may also apply to resistance provided by 'helpers'
      such as bacterial endosymbionts. We investigated the costs of symbiont-conferred
      resistance in the black bean aphid, Aphis fabae (Scopoli), which receives strong
      protection against the parasitoid Lysiphlebus fabarum from the defensive
      endosymbiont Hamiltonella defensa. Aphids infected with H. defensa were almost
      ten times more resistant to L. fabarum than genetically identical aphids without
      this symbiont, but in the absence of parasitoids, they had strongly reduced
      lifespans, resulting in lower lifetime reproduction. This is evidence for a
      substantial constitutive cost of harboring H. defensa. We did not observe any
      induced cost of symbiont-conferred resistance. On the contrary, symbiont
      protected aphids that resisted a parasitoid attack enjoyed increased longevity
      and lifetime reproduction compared with unattacked controls, whereas unprotected
      aphids suffered a reduction of longevity and reproduction after resisting an
      attack. This surprising result suggests that by focusing exclusively on the
      protection, we might underestimate the selective advantage of infection with H.
      defensa in the presence of parasitoids.

PMID- 23533104
TI  - Regioselective threefold aromatic substitution of benzoic acid derivatives by
      dearomatization, regioselective functionalization, and rearomatization.

PMID- 23533105
TI  - Results of infected total knee arthroplasty treated with arthroscopic debridement
      and continuous antibiotic irrigation system.
AB  - BACKGROUND: Arthroscopic debridement with continuous irrigation system was used
      with success in treating infective arthritis. We evaluated the effectiveness of
      arthroscopic debridement coupled with antibiotic continuous irrigation system in
      acute presentation of late infected total knee arthroplasty. MATERIALS AND
      METHODS: We performed a retrospective review of medical record of patients with
      acute presentation of late infected total knee arthroplasty who were treated by
      arthroscopic debridement coupled with continuous postoperative antibiotic
      irrigation system. RESULTS: Seventeen patients were included in our study. 15
      (88%) patients preserved their total knee prosthesis at mean of followup of 27.5
      months (range, 14-28 months). Two (12%) patients failed arthroscopic protocol and
      finally needed two stages revision. Our study showed an 88% prosthesis retention
      rate in patients with acute presentation of late prosthetic knee infection. No
      complication was associated with use of antibiotic irrigation system. CONCLUSION:
      Arthroscopic debridement combined with continuous antibiotic irrigation and
      suction is an effective treatment for patients with acute presentation of late
      infected total knee arthroplasty.

PMID- 23533106
TI  - Local field potentials reflect multiple spatial scales in V4.
AB  - Local field potentials (LFP) reflect the properties of neuronal circuits or
      columns recorded in a volume around a microelectrode (Buzsaki et al., 2012). The
      extent of this integration volume has been a subject of some debate, with
      estimates ranging from a few hundred microns (Katzner et al., 2009; Xing et al.,
      2009) to several millimeters (Kreiman et al., 2006). We estimated receptive
      fields (RFs) of multi-unit activity (MUA) and LFPs at an intermediate level of
      visual processing, in area V4 of two macaques. The spatial structure of LFP
      receptive fields varied greatly as a function of time lag following stimulus
      onset, with the retinotopy of LFPs matching that of MUAs at a restricted set of
      time lags. A model-based analysis of the LFPs allowed us to recover two distinct
      stimulus-triggered components: an MUA-like retinotopic component that originated
      in a small volume around the microelectrodes (~350 MUm), and a second component
      that was shared across the entire V4 region; this second component had tuning
      properties unrelated to those of the MUAs. Our results suggest that the LFP
      reflects neural activity across multiple spatial scales, which both complicates
      its interpretation and offers new opportunities for investigating the large-scale
      structure of network processing.

PMID- 23533107
TI  - Differential expression profiling and functional analysis of microRNAs through
      stage I-III papillary thyroid carcinoma.
AB  - OBJECTIVE: To elucidate the mechanisms undergoing the pathogenesis of PTC, this
      study try to find stage specific microRNAs (miRNAs) using microarray chip in
      stage I, II and III papillary thyroid carcinoma (PTC) tissues as well predict
      miRNAs binding target genes and their molecular functions. METHODS: PTC specimens
      of stage I, II, and III and their paired adjacent non-tumor tissue (one patient
      for each stage) were collected. The expressions of miRNAs were examined using
      miRNA microarray chip. The most significant changed miRNAs from microarray were
      verified by using quantitative RT-PCR. The Potential miRNAs regulating target
      genes and their preliminary biological functions were forecasted with variety
      function prediction software. RESULTS: Ten miRNAs exhibited sequential up
      regulation expression profiles and five miRNAs performed sequential down
      regulation throughout stage I to III (p<0.05). After normalization, Fifteen
      miRNAs showed significant different compared to adjacent non-tumor tissues
      (p<0.05). Among of them, the most significant up regulation and down regulation
      miRNAs were miR-146b-5p and miR-335, respectively. Both of them were verified
      with qRT-PCR. 34 target genes for miR-146-5p and 36 target genes for miR-335 was
      predicted. CONCLUSION: MicroRNA profile assay successfully detected a branch of
      differential expression miRNAs between PTC and normal tissue. Some of them also
      showed stage specific. Biological function analysis showed that target genes were
      involved in five aspects including cell proliferation, differentiation,
      apoptosis, cycle, and signaling transduction pathway, suggesting the regulatory
      role of abnormal expression of critical miRNAs in the pathogenesis of PTC.

PMID- 23533109
TI  - Prenatal diagnosis of partial trisomy 16p and its association with congenital
      diaphragmatic hernia.

PMID- 23533108
TI  - Targeting human serum fucome by an integrated liquid-phase multicolumn platform
      operating in "cascade" to facilitate comparative mass spectrometric analysis of
      disease-free and breast cancer sera.
AB  - A fully integrated platform was developed for capturing/fractionating human
      fucome from disease-free and breast cancer sera. It comprised a multicolumn
      operated by HPLC pumps and switching valves for the simultaneous depletion of
      high abundance proteins via affinity-based subtraction and the capturing of
      fucosylated glycoproteins via lectin affinity chromatography followed by the
      fractionation of the captured glycoproteins by reversed phase chromatography
      (RPC). Two lectin columns specific to fucose, namely Aleuria aurantia lectin
      (AAL) and Lotus tetragonolobus agglutinin (LTA) were utilized. The platform
      allowed the "cascading" of the serum sample from column-to-column in the liquid
      phase with no sample manipulation between the various steps. This guaranteed no
      sample loss and no propagation of experimental biases between the various
      columns. Finally, the fucome was fractionated by RPC yielding desalted fractions
      in volatile acetonitrile-rich mobile phase, which after vacuum evaporation were
      subjected to trypsinolysis for LC-MS/MS analysis. This permitted the
      identification of the differentially expressed proteins (DEP) in breast cancer
      serum yielding a broad panel of 35 DEP from the combined LTA and AAL captured
      proteins and a narrower panel of eight DEP that were commonly differentially
      expressed in both LTA and AAL fractions, which are considered as more
      representative of cancer altered fucome.

PMID- 23533110
TI  - Effects of freezing/thawing on the mechanical properties of decellularized lungs.
AB  - Lung bioengineering based on decellularized organ scaffolds is a potential
      alternative for transplantation. Freezing/thawing, a usual procedure in organ
      decellularization and storage could modify the mechanical properties of the lung
      scaffold and reduce the performance of the bioengineered lung when subjected to
      the physiological inflation-deflation breathing cycles. The aim of this study was
      to determine the effects of repeated freezing/thawing on the mechanical
      properties of decellularized lungs in the physiological pressure-volume regime
      associated with normal ventilation. Fifteen mice lungs (C57BL/6) were
      decellularized using a conventional protocol not involving organ freezing and
      based on sodium dodecyl sulfate detergent. Subsequently, the mechanical
      properties of the acellular lungs were measured before and after subjecting them
      to three consecutive cycles of freezing/thawing. The resistance (RL ) and
      elastance (EL ) of the decellularized lungs were computed by linear regression
      fitting of the recorded signals (tracheal pressure, flow, and volume) during
      mechanical ventilation. RL was not significantly modified by freezing-thawing:
      from 0.88 +/- 0.37 to 0.90 +/- 0.38 cmH2 O.s.mL(-1) (mean +/- SE). EL slightly
      increased from 64.4 +/- 11.1 to 73.0 +/- 16.3 cmH2 O.mL(-1) after the three
      freeze-thaw cycles (p = 0.0013). In conclusion, the freezing/thawing process that
      is commonly used for both organ decellularization and storage induces only minor
      changes in the ventilation mechanical properties of the organ scaffold.

PMID- 23533112
TI  - Likelihood is high that the BMJ's survey of the Liverpool care pathway is biased.

PMID- 23533111
TI  - Characterization of Aphanizomenon ovalisporum amidinotransferase involved in
      cylindrospermopsin synthesis.
AB  - An increasing abundance of Aphanizomenon ovalisporum in water bodies from diverse
      world regions has been reported in the last few years, with the majority of the
      isolated strains producing the toxin cylindrospermopsin (CYN), leading to a rise
      in ecological and health risks. The understanding of CYN synthesis is crucial in
      the control of CYN production. An amidinotransferase (AMDT) seems to be the first
      enzyme involved in the synthesis of CYN. In this study, we have cloned and
      overexpressed the aoaA gene from the constitutive CYN producer A. ovalisporum UAM
      MAO. The recombinant purified AoaA was characterized, confirming that it is an l
      arginine:glycine AMDT. It shows an optimal activity between 32 and 37 degrees C,
      at pH from 8 to 9. The activity exhibits a mixed (ping-pong/sequential) kinetic
      mechanism, and is inhibited by the reaction product guanidine acetate (GAA) in a
      noncompetitive manner. Mg(2+) stimulates AoaA activity while Co(2+) and Mn(2+)
      inhibit it. AoaA conserves the critical residues of the catalytic site and
      substrate specificity of AMDTs, as the previously reported AMDT from
      Cylindrospermopsis raciborskii Cyr. Both proteins can be included in a new group
      of prokaryotic AMDTs involved in CYN production.

PMID- 23533113
TI  - The NHS must work more efficiently throughout the week.

PMID- 23533114
TI  - Change the culture around death and dying in acute hospitals.

PMID- 23533115
TI  - Author's reply to Solomon.

PMID- 23533116
TI  - Evidence base needs to be developed for the whole process of end of life care.

PMID- 23533117
TI  - Protests about having to structure time off to enable the NHS to work at weekends
      as it does in the week may be hypocritical.

PMID- 23533118
TI  - The NHS working at weekends as it does during the week is a non-starter.

PMID- 23533119
TI  - Training of young surgeons would be problematic if the NHS worked at weekends as
      it does during the week.

PMID- 23533120
TI  - Suicide is leading cause of death in young Indian women, finds international
      study.

PMID- 23533121
TI  - Indian government allocates nearly half its disaster budget for drought relief in
      Maharashtra.

PMID- 23533122
TI  - Surgery or physiotherapy for meniscal tears?

PMID- 23533123
TI  - Adults with severe mental illness need tailor made help to lose weight.

PMID- 23533124
TI  - No link between vitamin D in pregnancy and bone health in children.

PMID- 23533125
TI  - Revisit standards for approving long term drugs.

PMID- 23533126
TI  - Two thirds of Welsh district hospitals have higher than predicted mortality,
      figures show.

PMID- 23533127
TI  - Clofazimine should be used in all cases of leprosy, says Indian research council.

PMID- 23533128
TI  - Academy of Medical Royal Colleges' reply to open letter.

PMID- 23533129
TI  - Telehealth can be beneficial when used properly, say experts.

PMID- 23533130
TI  - Sequester cuts will hit medical care and research.

PMID- 23533131
TI  - Reducing interns' duty hours is problematic, studies show.

PMID- 23533132
TI  - Healthwatch must prove its worth to survive in testing times.

PMID- 23533133
TI  - Immunophenotypic, immunocytochemistry, ultrastructural, and cytogenetic
      characterization of mesenchymal stem cells from equine bone marrow.
AB  - The aim of this study was to isolate, culture, and characterize mesenchymal stem
      cells (MSCs) from horse bone marrow (BM) using the techniques of flow cytometry,
      immunocytochemistry, cytogenetics, and electron microscopy. Immunophenotypic
      analysis revealed the presence of MSCs with high expression of the CD90 marker,
      lower expression of the CD44 marker, and absent expression of the CD34 marker. In
      assays of differentiation, the positive response to osteogenic (OST),
      chondrogenic (CDG), and adipogenic (ADP) differentiation signals was observed and
      characterized by deposition of calcium-rich extracellular matrix (OST),
      proteoglycans and collagen II (CDG) and intracellular deposition of fat drops
      (ADP). In immunocytochemical characterization, MSCs were immunopositive for CD44,
      vimentin, and PCNA, and they were negative for CD13. In the ultrastructural
      analysis of MSCs, the most outstanding characteristic was the presence of rough
      endoplasmic reticulum with very dilated cisterns filled with a low electrodensity
      material. Additionally, MSCs had normal karyotypes (2n = 64) as evidenced by
      cytogenetic analysis, and aneuploidy in metaphase was not observed. The protocols
      for isolating, culturing, and characterizing equine MSCs used in this study were
      shown to be appropriate for the production of a cell population with a good
      potential for differentiation and without aneuploidy that can be used to study
      future cellular therapies.

PMID- 23533134
TI  - Luminescent gelatin nanospheres by encapsulating CdSe quantum dots.
AB  - Quantum dots (QDs) have been encapsulated within gelatin nanoparticles (GNPs),
      which gives GNPs fluorescent properties and improves the biocompatibility of QDs.
      Hydrophilic CdSe QDs were produced through thermodecomposition following the
      ligand-exchange method, and were then encapsulated in GNPs. The results of high
      resolution transmission electron microscopy and transmission electron microscopy
      show that CdSe QDs and QDs-encapsulated GNPs (QDs-GNPs) have average diameters of
      5 +/- 1 and 150 +/- 10 nm, respectively. Results of both high-resolution
      transmission electron microscopy and confocal laser scanning microscopy indicate
      that CdSe QDs are successfully encapsulated within GNPs. The QDs-GNPs have
      distinctive fluorescent properties with maximum emission at 654 nm, with a 24 nm
      red-shift compared with hydrophilic mercaptoundecanoic acid (MUA)-modified QDs.
      In addition, an in vitro cytotoxicity test shows that QDs-GNPs do not have any
      toxic effect on cells. It is expected that QDs-GNPs might be an excellent
      candidate as a contrast agent in bio-imaging.

PMID- 23533135
TI  - Analysis of mobile phone design features affecting radiofrequency power absorbed
      in a human head phantom.
AB  - The US FCC mandates the testing of all mobile phones to demonstrate compliance
      with the rule requiring that the peak spatial SAR does not exceed the limit of
      1.6 W/kg averaged over any 1 g of tissue. These test data, measured in phantoms
      with mobile phones operating at maximum antenna input power, permitted us to
      evaluate the variation in SARs across mobile phone design factors such as shape
      and antenna design, communication technology, and test date (over a 7-year
      period). Descriptive statistical summaries calculated for 850 MHz and 1900 MHz
      phones and ANOVA were used to evaluate the influence of the foregoing factors on
      SARs. Service technology accounted for the greatest variability in compliance
      test SARs that ranged from AMPS (highest) to CDMA, iDEN, TDMA, and GSM (lowest).
      However, the dominant factor for SARs during use is the time-averaged antenna
      input power, which may be much less than the maximum power used in testing. This
      factor is largely defined by the communication system; e.g., the GSM phone
      average output can be higher than CDMA by a factor of 100. Phone shape, antenna
      type, and orientation of a phone were found to be significant but only on the
      order of up to a factor of 2 (3 dB). The SAR in the tilt position was
      significantly smaller than for touch. The side of the head did not affect SAR
      levels significantly. Among the remaining factors, external antennae produced
      greater SARs than internal ones, and brick and clamshell phones produced greater
      SARs than slide phones. Assuming phone design and usage patterns do not change
      significantly over time, we have developed a normalization procedure and formula
      that permits reliable prediction of the relative SAR between various
      communication systems. This approach can be applied to improve exposure
      assessment in epidemiological research.

PMID- 23533136
TI  - Ligand-directed control over crystal structures of inorganic-organic frameworks
      and formation of solid solutions.

PMID- 23533137
TI  - Transvaginal sonographic assessment of cervical length and wedging for predicting
      outcome of labor induction at term: a systematic review and meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis to assess the
      predictive capacity of transvaginal sonographic assessment of the cervix for the
      outcome of induction of labor. METHODS: We searched MEDLINE, EMBASE and the
      Cochrane Library, and manually searched reference lists of review articles and
      eligible primary articles. Studies in all languages were eligible if published in
      full. Two reviewers independently selected studies and extracted data on study
      characteristics, quality and test accuracy. We then calculated pooled
      sensitivities and specificities (with 95% CIs) and summary receiver-operating
      characteristics (sROC) curves. Outcome measures were test accuracy of
      sonographically measured cervical length and cervical wedging for Cesarean
      section, not achieving vaginal delivery within 24 h and not achieving active
      labor. RESULTS: We included 31 studies reporting on both cervical length and
      outcome of delivery. The quality of the included studies was mediocre.
      Sensitivity of cervical length in the prediction of Cesarean delivery ranged from
      0.14 to 0.92 and specificity ranged from 0.35 to 1.00. The estimated sROC curve
      for cervical length indicated a limited predictive capacity in the prediction of
      Cesarean delivery. Summary estimates of sensitivity/specificity combinations of
      cervical length at different cut-offs for Cesarean delivery were 0.82/0.34,
      0.64/0.74 and 0.13/0.95 for 20, 30 and 40 mm, respectively. For cervical wedging
      in the prediction of failed induction of labor summary point estimates of
      sensitivity/specificity were 0.37/0.80. CONCLUSIONS: Cervical length and cervical
      wedging as measured sonographically at or near term have moderate capacity to
      predict the outcome of delivery after induction of labor.

PMID- 23533138
TI  - From Peptidome to PRIDE: public proteomics data migration at a large scale.
AB  - The PRIDE database, developed and maintained at the European Bioinformatics
      Institute (EBI), is one of the most prominent data repositories dedicated to high
      throughput MS-based proteomics data. Peptidome, developed by the National Center
      for Biotechnology Information (NCBI) as a sibling resource to PRIDE, was
      discontinued due to funding constraints in April 2011. A joint effort between the
      two teams was started soon after the Peptidome closure to ensure that data were
      not "lost" to the wider proteomics community by exporting it to PRIDE. As a
      result, data in the low terabyte range have been migrated from Peptidome to PRIDE
      and made publicly available under experiment accessions 17 900-18 271,
      representing 54 projects, ~53 million mass spectra, ~10 million peptide
      identifications, ~650,000 protein identifications, ~1.1 million biologically
      relevant protein modifications, and 28 species, from more than 30 different labs.

PMID- 23533139
TI  - Performance of conical abutment (Morse Taper) connection implants: a systematic
      review.
AB  - In this systematic review, we aimed to compare conical versus nonconical implant
      abutment connection systems in terms of their in vitro and in vivo performances.
      An electronic search was performed using PubMed, Embase, and Medline databases
      with the logical operators: "dental implant" AND "dental abutment" AND ("conical"
      OR "taper" OR "cone"). Names of the most common conical implant-abutment
      connection systems were used as additional key words to detect further data. The
      search was limited to articles published up to November 2012. Recent publications
      were also searched manually in order to find any relevant studies that might have
      been missed using the search criteria noted above. Fifty-two studies met the
      inclusion criteria and were included in this systematic review. As the data and
      methods, as well as types of implants used was so heterogeneous, this mitigated
      against the performance of meta-analysis. In vitro studies indicated that conical
      and nonconical abutments showed sufficient resistance to maximal bending forces
      and fatigue loading. However, conical abutments showed superiority in terms of
      seal performance, microgap formation, torque maintenance, and abutment stability.
      In vivo studies (human and animal) indicated that conical and nonconical systems
      are comparable in terms of implant success and survival rates with less marginal
      bone loss around conical connection implants in most cases. This review indicates
      that implant systems using a conical implant-abutment connection, provides better
      results in terms of abutment fit, stability, and seal performance. These design
      features could lead to improvements over time versus nonconical connection
      systems.

PMID- 23533141
TI  - Ethnic disparities in disability among middle-aged and older israeli adults: the
      role of socioeconomic disadvantage and traumatic life events.
AB  - OBJECTIVE: We examined the contribution of socioeconomic disadvantage and
      traumatic life events to ethnic disparities in disability among Israeli adults.
      METHOD: We used data from the Survey of Health, Aging and Retirement in Europe
      (SHARE-Israel), a sample of Israeli adults aged 50 or older (N = 1,546).
      Disability measures included functional limitations, limitations in activities of
      daily living (ADL), and limitations in instrumental activities of daily living
      (IADL). RESULTS: Arabs and immigrants from the Former Soviet Union (FSU)
      experienced higher rates of functional limitations and limitations in IADLs
      compared to veteran Jews. The rate of having limitations in ADLs was similar for
      Arabs and veteran Jews, but was higher for FSU immigrants compared to veteran
      Jews. Inclusion of education, income, and traumatic life events attenuated, but
      did not eliminate ethnic disparities in disability. DISCUSSION: Identifying
      factors driving ethnic health disparities in Israel is imperative if we hope to
      achieve health equity.

PMID- 23533140
TI  - Truncation of type IV pilin induces mucoidy in Pseudomonas aeruginosa strain
      PAO579.
AB  - Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the
      overproduction of alginate, a surface polysaccharide, to form biofilms in vivo.
      Overproduction of alginate, also known as mucoidy, affords the bacterium
      protection from the host's defenses and facilitates the establishment of chronic
      lung infections in individuals with cystic fibrosis. Expression of the alginate
      biosynthetic operon is primarily controlled by the alternative sigma factor AlgU
      (AlgT/sigma(22) ). In a nonmucoid strain, AlgU is sequestered by the
      transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be
      released from MucA via regulated intramembrane proteolysis by proteases AlgW and
      MucP causing the conversion to mucoidy. Pseudomonas aeruginosa strain PAO579, a
      derivative of the nonmucoid strain PAO1, is mucoid due to an unidentified
      mutation (muc-23). Using whole genome sequencing, we identified 16 nonsynonymous
      and 15 synonymous single nucleotide polymorphisms (SNP). We then identified three
      tandem single point mutations in the pilA gene (PA4525), as the cause of mucoidy
      in PAO579. These tandem mutations generate a premature stop codon resulting in a
      truncated version of PilA (PilA(108) ), with a C-terminal motif of phenylalanine
      threonine-phenylalanine (FTF). Inactivation of pilA(108) confirmed it was
      required for mucoidy. Additionally, algW and algU were also required for mucoidy
      of PAO579. Western blot analysis indicated that MucA was less stable in PAO579
      than nonmucoid PAO1 or PAO381. The mucoid phenotype and high PalgU and PalgD
      promoter activities of PAO579 require pilA(108) , algW, algU, and rpoN encoding
      the alternative sigma factor sigma(54) . We also observed that RpoN regulates
      expression of algW and pilA in PAO579. Together, these results suggest that
      truncation in type IV pilin in P. aeruginosa strain PAO579 can induce mucoidy
      through an AlgW/AlgU-dependent pathway.

PMID- 23533143
TI  - Quantitative zonal differentiation of articular cartilage by microscopic magnetic
      resonance imaging, polarized light microscopy, and Fourier-transform infrared
      imaging.
AB  - This study aimed to synchronize the zonal differentiation of the full-thickness
      articular cartilage by three micro-imaging techniques, namely microscopic
      magnetic resonance imaging (uMRI), polarized light microscopy (PLM), and Fourier
      transform infrared imaging (FTIRI). Eighteen cartilage-bone blocks from three
      canine humeral joints were imaged by: (a) uMRI T2 relaxation at 0 degrees  and 55
      degrees  orientations in a 7 T magnetic field, (b) PLM optical retardation and
      azimuthal angle, and (c) FTIRI amide I and amide II anisotropies at 0 degrees 
      and 90 degrees  polarizations relative to the articular surface. In addition,
      uMRI T1 relaxation was imaged before and after the tissue being immersed in
      gadolinium (contrast agent) solution, to calculate the proteoglycan
      concentration. A set of previously established criteria in cartilage imaging was
      revised. The new criteria could simultaneously correlate the thicknesses of the
      three consecutive subtissue zones in articular cartilage among these imaging
      techniques.

PMID- 23533144
TI  - Time passes yet errors remain: comments on the structure of N10
      formyltetrahydrofolate synthetase.

PMID- 23533145
TI  - In-depth proteomic analyses of exosomes isolated from expressed prostatic
      secretions in urine.
AB  - Expressed prostatic secretions (EPS) are proximal fluids of the prostate that are
      increasingly being utilized as a clinical source for diagnostic and prognostic
      assays for prostate cancer (PCa). These fluids contain an abundant amount of
      microvesicles reflecting the secretory function of the prostate gland, and their
      protein composition remains poorly defined in relation to PCa. Using expressed
      prostatic secretions in urine (EPS-urine), exosome preparations were
      characterized by a shotgun proteomics procedure. In pooled EPS-urine exosome
      samples, ~900 proteins were detected. Many of these have not been previously
      observed in the soluble proteome of EPS generated by our labs or other related
      exosome proteomes. We performed systematic comparisons of our data against
      previously published, prostate-related proteomes, and global annotation analyses
      to highlight functional processes within the proteome of EPS-urine derived
      exosomes. The acquired proteomic data have been deposited to the Tranche
      repository and will lay the foundation for more extensive investigations of PCa
      derived exosomes in the context of biomarker discovery and cancer biology.

PMID- 23533146
TI  - Quality of life of patients with neurodermatitis.
AB  - BACKGROUND: Neurodermatitis is a common chronic skin disease. Although not life
      threatening, it can produce an important psychosocial burden, sleep disturbance
      and sexual dysfunction. Patients with neurodermatitis tend to have poor social
      skills or interpersonal resources and a lack of flexibility. However quality of
      life (QoL) of patients with neurodermatitis has seldom investigated. The
      objective of this study is to assess the impact of neurodermatitis on patients'
      QoL using the Dermatology Life Quality Index questionnaire, and assess its
      feasibility and internal consistency. METHODS: One hundred and fifty consecutive
      outpatients seeking treatment for neurodermatitis and 250 patients with psoriasis
      in the Department of Dermatology, the Second Hospital of Xi'an Jiaotong
      University, were assessed for eligibility for this prospective study from July 1,
      2011 to September 30, 2011. Demographic data and disease-related characteristics
      were collected. RESULTS: The overall mean DLQI score for neurodermatits (9.34)
      was lower than that for psoriasis (13.32) (P < 0.001). Patients with
      neurodermatitis scored significantly lower for all items except Q1 (symptoms) and
      Q9 (sexual difficulties). No strong relationship between disease-related
      characteristics and quality of life could be found. The inter-item correlation
      averaged 0.415 and Cronbach's alpha was 0.889, indicating high internal
      consistency. CONCLUSION: This is the first study to attempt to measure the impact
      of neurodermatitis for both male and female patients on QoL. Neurodermatitis
      moderately affected the QoL of the patients.

PMID- 23533147
TI  - Inferring network properties of cortical neurons with synaptic coupling and
      parameter dispersion.
AB  - Computational models at different space-time scales allow us to understand the
      fundamental mechanisms that govern neural processes and relate uniquely these
      processes to neuroscience data. In this work, we propose a novel
      neurocomputational unit (a mesoscopic model which tell us about the interaction
      between local cortical nodes in a large scale neural mass model) of bursters that
      qualitatively captures the complex dynamics exhibited by a full network of
      parabolic bursting neurons. We observe that the temporal dynamics and fluctuation
      of mean synaptic action term exhibits a high degree of correlation with the
      spike/burst activity of our population. With heterogeneity in the applied drive
      and mean synaptic coupling derived from fast excitatory synapse approximations we
      observe long term behavior in our population dynamics such as partial
      oscillations, incoherence, and synchrony. In order to understand the origin of
      multistability at the population level as a function of mean synaptic coupling
      and heterogeneity in the firing rate threshold we employ a simple generative
      model for parabolic bursting recently proposed by Ghosh et al. (2009). Further,
      we use here a mean coupling formulated for fast spiking neurons for our analysis
      of generic model. Stability analysis of this mean field network allow us to
      identify all the relevant network states found in the detailed biophysical model.
      We derive here analytically several boundary solutions, a result which holds for
      any number of spikes per burst. These findings illustrate the role of
      oscillations occurring at slow time scales (bursts) on the global behavior of the
      network.

PMID- 23533148
TI  - Night-to-night consistency of at-home nocturnal pulse oximetry testing for
      obstructive sleep apnea in children.
AB  - RATIONALE: At-home nocturnal pulse oximetry has a high positive predictive value
      (PPV) for polysomnographically-diagnosed obstructive sleep apnea (OSA) but no
      studies have been published testing the night-to-night consistency of at-home
      nocturnal pulse oximetry for the evaluation of suspected OSA in children. We
      therefore determined the night-to-night consistency of nocturnal pulse oximetry
      as a diagnostic test for OSA in children. METHODS: We prospectively studied 148
      children (96 male) aged 4.9 +/- 2.4 (1.2-11.8) years, referred for suspected OSA.
      To evaluate night-to-night consistency, we compared an oximetry analysis method,
      the McGill Oximetry Score (MOS), from two consecutive at-home nocturnal pulse
      oximetry recordings. RESULTS: Pulse oximetry metrics were similar on the two
      nights. The MOS on the two nights showed excellent night-to-night consistency
      when analyzed as positive for OSA versus inconclusive, 143/148 (Spearman's
      correlation coefficient = 0.90). A more detailed analysis using four categories
      (MOS 1, 2, 3, and 4) of OSA severity showed very good night-to-night agreement,
      133/148 (Spearman's correlation coefficient = 0.91). Variability was increased in
      children younger than 4 years of age compared to older children. CONCLUSIONS:
      Night-to-night consistency of nocturnal pulse oximetry as a diagnostic test for
      OSA showed excellent agreement. Night-to-night consistency of pulse oximetry, as
      analyzed by the MOS, for diagnosis and severity evaluation further validates this
      abbreviated testing method for pediatric OSA. Polysomnography (PSG) is required
      to rule in or rule out OSA in children if a single night oximetry testing is
      inconclusive.

PMID- 23533149
TI  - Preparation of chitosan/silk fibroin/hydroxyapatite porous scaffold and its
      characteristics in comparison to bi-component scaffolds.
AB  - Composite porous scaffolds have attracted extensive attention in the biomedical
      material field. The aim of this research was to prepare a novel tri-component
      composite porous scaffold and to evaluate its relevant properties. The porous
      scaffold was composed of chitosan (CS), silk fibroin (SF), and nanohydroxyapatite
      particles (nHA), which we named CS/SF/nHA scaffold and prepared via salt
      fractionation method combined with lyophilization. The porous structure was
      achieved using a porogen (salt), and the pore size was controlled by the size of
      porogen. To evaluate the characteristics of the tri-component scaffold, three bi
      component scaffolds, CS/SF, CS/nHA, and SF/nHA, were simultaneously prepared for
      comparison. The scaffolds were subjected to morphological, micro-structural, and
      biodegradation analyses. Results demonstrated that all of the scaffolds had pore
      sizes of 100-300 MUm and a porosity of 90.5-96.1%. The biodegradation
      characteristics of all scaffolds meet the requirements of good biomedical
      materials. The investigation of the mechanical properties showed that the tri
      component scaffold has better properties than the bi-component scaffolds. The in
      vitro biocompatibility with osteoblast-like MG-63 cells showed that all the
      scaffolds are suitable for cell attachment and proliferation; however, the
      CS/SF/nHA composite porous scaffold is much more effective than the others.

PMID- 23533151
TI  - A facile strategy for selective incorporation of phosphoserine into histones.

PMID- 23533150
TI  - Brief alcohol exposure alters transcription in astrocytes via the heat shock
      pathway.
AB  - Astrocytes are critical for maintaining homeostasis in the central nervous system
      (CNS), and also participate in the genomic response of the brain to drugs of
      abuse, including alcohol. In this study, we investigated ethanol regulation of
      gene expression in astrocytes. A microarray screen revealed that a brief exposure
      of cortical astrocytes to ethanol increased the expression of a large number of
      genes. Among the alcohol-responsive genes (ARGs) are glial-specific immune
      response genes, as well as genes involved in the regulation of transcription,
      cell proliferation, and differentiation, and genes of the cytoskeleton and
      extracellular matrix. Genes involved in metabolism were also upregulated by
      alcohol exposure, including genes associated with oxidoreductase activity,
      insulin-like growth factor signaling, acetyl-CoA, and lipid metabolism. Previous
      microarray studies performed on ethanol-treated hepatocyte cultures and mouse
      liver tissue revealed the induction of almost identical classes of genes to those
      identified in our microarray experiments, suggesting that alcohol induces similar
      signaling mechanisms in the brain and liver. We found that acute ethanol exposure
      activated heat shock factor 1 (HSF1) in astrocytes, as demonstrated by the
      translocation of this transcription factor to the nucleus and the induction of a
      family of known HSF1-dependent genes, the heat shock proteins (Hsps).
      Transfection of a constitutively transcriptionally active Hsf1 construct into
      astrocytes induced many of the ARGs identified in our microarray study supporting
      the hypothesis that HSF1 transcriptional activity, as part of the heat shock
      cascade, may mediate the ethanol induction of these genes. These data indicate
      that acute ethanol exposure alters gene expression in astrocytes, in part via the
      activation of HSF1 and the heat shock cascade.

PMID- 23533152
TI  - Modeling and simulation of biological systems from image data.
AB  - This essay provides an introduction to the terminology, concepts, methods, and
      challenges of image-based modeling in biology. Image-based modeling and
      simulation aims at using systematic, quantitative image data to build predictive
      models of biological systems that can be simulated with a computer. This allows
      one to disentangle molecular mechanisms from effects of shape and geometry.
      Questions like "what is the functional role of shape" or "how are biological
      shapes generated and regulated" can be addressed in the framework of image-based
      systems biology. The combination of image quantification, model building, and
      computer simulation is illustrated here using the example of diffusion in the
      endoplasmic reticulum.

PMID- 23533153
TI  - Management of velopharyngeal insufficiency using double opposing z-plasty in
      patients undergoing primary two-flap palatoplasty.
AB  - BACKGROUND: Velopharyngeal insufficiency (VPI) may persist after primary repair
      of the cleft palate, and surgical correction is necessary in many cases. The
      purpose of this study is to evaluate the effect of double opposing Z-plasty (DOZ)
      in cleft palate patients suffering from VPI after primary two-flap palatoplasty.
      METHODS: Between March 1999 and August 2005, we identified 82 patients who
      underwent two-flap palatoplasty for cleft palate repair. After excluding the
      patients with congenital syndrome and mental retardation, 13 patients were
      included in the final study group. The average age of the patients who underwent
      DOZ at was 5 years and 1 month. Resonance, nasal emission, and articulation were
      evaluated by a speech pathologist. The velopharyngeal gaps were measured before
      and after surgery. RESULTS: Six patients attained normal speech capabilities
      after DOZ. The hypernasality grade was significantly improved after surgery in
      all of the patients (P=0.0015). Whereas nasal emission disappeared in 8 patients
      (61.5%), it was diminished but still persisted in the remaining 5 patients.
      Articulation was improved in all of the cases. In two cases, the velopharyngeal
      gap was measured using a ruler. The gap decreased from 11.5 to 7 mm in one case,
      and from 12.5 to 8 mm in the second case. CONCLUSIONS: The use of DOZ as a
      surgical option to correct VPI has many advantages compared with other
      procedures. These include short surgery time, few troublesome complications, and
      no harmful effects on the dynamic physiological functioning of the pharynx. This
      study shows that DOZ can be another option for surgical treatment of patients
      with VPI after two-flap palatoplasty.

PMID- 23533154
TI  - Quantitative appraisal of ventricular cerebrospinal fluid biomarkers in
      neuropathologically diagnosed Parkinson's disease cases lacking Alzheimer's
      disease pathology.
AB  - Identifying biomarkers that distinguish Parkinson's disease (PD) from normal
      control (NC) individuals has the potential to increase diagnostic sensitivity for
      the detection of early-stage PD. A previous proteomic study identified potential
      biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from
      neuropathologically diagnosed PD subjects lacking Alzheimer's disease (AD)
      neuropathology. In the present study, we assessed these biomarkers as well as p
      tau(181), Abeta42, and S100B by ELISA in PD (n = 43) and NC (n = 49) cases. The p
      tau(181)/Abeta42 ratio and ApoA-1 showed statistically significant differences
      between groups. Multiple regression analysis demonstrated that p-tau(181)/Abeta42
      had a significant odds ratio: OR = 1.42 (95% confidence interval [CI], 1.12
      1.84), P = 0.006. Among the molecules investigated, intriguing correlations were
      observed that require further investigation. Our results suggest coexistent AD
      CSF biomarkers within the PD group notwithstanding that it was selected to
      minimize AD neuropathological lesions.

PMID- 23533155
TI  - International research partnerships in occupational therapy: a Canadian-Zambian
      case study.
AB  - The country of Zambia's Sixth National Development Plan includes many objectives
      related to participation and health that align with values underlying
      occupational therapy. Given this link, occupational therapy research has the
      potential to advance the Sixth National Development Plan and thereby enhance the
      participation and health of Zambians. However, there is neither a school of
      occupational therapy nor many occupational therapists working in Zambia. Using an
      example of a global research partnership between Canadian occupational therapy
      researchers and Zambian researchers, this paper examines the partnership using
      four criteria for global health research in order to derive lessons for future
      occupational therapy research partnerships. Implications for future occupational
      therapy research partnerships include the need for partners to combine their
      complementary skills and knowledge so that they may collaborate in mutually
      beneficial ways to address global health challenges and expand the reach of
      occupational therapy perspectives.

PMID- 23533156
TI  - Post-bronchiolitis asthma risk-hospitalized infants need more precise risk
      definition.

PMID- 23533157
TI  - Tumorigenic potential of miR-18A* in glioma initiating cells requires NOTCH-1
      signaling.
AB  - Stem cell-like properties of glioma initiating cells (GiCs) fuel glioblastoma
      (GBM) development by providing the different cell types that comprise the tumor.
      It is therefore likely that the molecular circuitries that regulate their
      decision to self-renew or commit to a more differentiated state may offer targets
      for future innovative therapies. In previous micro-RNA profiling studies to
      search for regulators of stem cell plasticity, we identified miR-18a* as a
      potential candidate and its expression correlated with the stemness state. Here,
      using human GiCs we found that miR-18a* expression promotes clonal proliferation
      in vitro and tumorigenicity in vivo. Mechanistically, ERK-dependent induction of
      miR-18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH,
      thus enhancing the level of activated NOTCH-1. Activated NOTCH-1 in turn is
      required for sustained ERK activation. This feed-forward loop, driven by miR
      18a*, is required to turn on the SHH-GLI-NANOG network, essential for GiC self
      renewal. Hence, by tightly regulating expression of DLL3, miR-18a* constitutes an
      important signaling mediator for fine tuning the level of GiC self-renewal.

PMID- 23533159
TI  - Does elevated pCO2 affect reef octocorals?
AB  - Increasing anthropogenic pCO2 alters seawater chemistry, with potentially severe
      consequences for coral reef growth and health. Octocorals are the second most
      important faunistic component in many reefs, often occupying 50% or more of the
      available substrate. Three species of octocorals from two families were studied
      in Eilat (Gulf of Aqaba), comprising the zooxanthellate Ovabunda macrospiculata
      and Heteroxenia fuscescens (family Xeniidae), and Sarcophyton sp. (family
      Alcyoniidae). They were maintained under normal (8.2) and reduced (7.6 and 7.3)
      pH conditions for up to 5 months. Their biolological features, including protein
      concentration, polyp weight, density of zooxanthellae, and their chlorophyll
      concentration per cell, as well as polyp pulsation rate, were examined under
      conditions more acidic than normal, in order to test the hypothesis that rising
      pCO2 would affect octocorals. The results indicate no statistically significant
      difference between the octocorals exposed to reduced pH values compared to the
      control. It is therefore suggested that the octocorals' tissue may act as a
      protective barrier against adverse pH conditions, thus maintaining them unharmed
      at high levels of pCO2.

PMID- 23533158
TI  - Human hippocampal energy metabolism is impaired during cognitive activity in a
      lipid infusion model of insulin resistance.
AB  - Neuronal glucose uptake was thought to be independent of insulin, being
      facilitated by glucose transporters GLUT1 and GLUT3, which do not require insulin
      signaling. However, it is now known that components of the insulin-mediated
      glucose uptake pathway, including neuronal insulin synthesis and the insulin
      dependent glucose transporter GLUT4, are present in brain tissue, particularly in
      the hippocampus. There is considerable recent evidence that insulin signaling is
      crucial to optimal hippocampal function. The physiological basis, however, is not
      clear. We propose that while noninsulin-dependent GLUT1 and GLUT3 transport is
      adequate for resting needs, the surge in energy use during sustained cognitive
      activity requires the additional induction of insulin-signaled GLUT4 transport.
      We studied hippocampal high-energy phosphate metabolism in eight healthy
      volunteers, using a lipid infusion protocol to inhibit insulin signaling.
      Contrary to conventional wisdom, it is now known that free fatty acids do cross
      the blood-brain barrier in significant amounts. Energy metabolism within the
      hippocampus was assessed during standardized cognitive activity. (31)Phosphorus
      magnetic resonance spectroscopy was used to determine the phosphocreatine (PCr)
      to-adenosine triphosphate (ATP) ratio. This ratio reflects cellular energy
      production in relation to concurrent cellular energy expenditure. With lipid
      infusion, the ratio was significantly reduced during cognitive activity (PCr/ATP
      1.0 +/- 0.4 compared with 1.4 +/- 0.4 before infusion, P = 0.01). Without lipid
      infusion, there was no reduction in the ratio during cognitive activity (PCr/ATP
      1.5 +/- 0.3 compared with 1.4 +/- 0.4, P = 0.57). This provides supporting
      evidence for a physiological role for insulin signaling in facilitating increased
      neuronal glucose uptake during sustained cognitive activity. Loss of this
      response, as may occur in type 2 diabetes, would lead to insufficient neuronal
      energy availability during cognitive activity.

PMID- 23533160
TI  - Human amniotic fluid stem cells protect rat lungs exposed to moderate hyperoxia.
AB  - BACKGROUND: Treatment of bronchopulmonary dysplasia (BPD) remains as yet an unmet
      clinical need and recently stem cells have been proposed as a therapeutic tool in
      animal models. We investigated the role of amniotic fluid stem cells (AFS) in an
      adult rat model of hyperoxia lung injury. METHODS: Fifty Sprague-Dawley rats
      were, at birth, randomly exposed to moderate hyperoxia or room air for 14 days
      and a single dose of human amniotic fluid stem (hAFS) or human Fibroblasts (hF),
      cells was delivered intratracheally (P21). At P42 animals were euthanized and
      lung tissue examined using histology, immunohistochemistry, PCR, and ELISA. hAFS
      cells characterization and homing were studied by immunofluorescence. RESULTS: In
      rats treated with hAFS and hF cells 16S human rRNA fragment was detected. Despite
      a low level of pulmonary hAFS cell retention (1.43 +/- 0.2% anti-human
      mitochondria-positive cells), the lungs of the treated animals revealed higher
      secondary crest numbers and lower mean linear intercept and alveolar size, than
      those exposed to hyperoxia, those left untreated or treated with hF cells. Except
      for those treated with hAFS cells, moderate hyperoxia induced an increase in
      protein content of IL-6, IL-1beta, as well as IF-gamma and TGF-1beta in lung
      tissues. High VEGF expression and arrangement of capillary architecture in hAFS
      cell group were also detected. CONCLUSIONS: Treatment with hAFS cells has a
      reparative potential through active involvement of cells in alveolarization and
      angiogenesis. A downstream paracrine action was also taken into account, in order
      to understand the immunodulatory response.

PMID- 23533161
TI  - Access to intrinsically glucoside-based microspheres with boron affinity.
AB  - Intrinsically glucoside-based microspheres are prepared in olive oil via a water
      in oil inverse suspension polymerization. The microspheres are characterized by
      scanning electron microscopy (SEM), Fourier transform infrared (FTIR) microscopy,
      and X-ray photoelectron spectroscopy (XPS), evidencing the intrinsic glucose
      character of the spheres. A novel boronic acid fluorescent molecule was
      subsequently conjugated to the microspheres in an aqueous environment, exhibiting
      the spatial and uniform distribution of glucoside as well as the affinity of the
      microspheres to bind with boron, evidenced via fluorescence spectroscopy
      measurements.

PMID- 23533162
TI  - Monte Carlo N Particle code - Dose distribution of clinical electron beams in
      inhomogeneous phantoms.
AB  - Electron dose distributions calculated using the currently available analytical
      methods can be associated with large uncertainties. The Monte Carlo method is the
      most accurate method for dose calculation in electron beams. Most of the clinical
      electron beam simulation studies have been performed using non- MCNP [Monte Carlo
      N Particle] codes. Given the differences between Monte Carlo codes, this work
      aims to evaluate the accuracy of MCNP4C-simulated electron dose distributions in
      a homogenous phantom and around inhomogeneities. Different types of phantoms
      ranging in complexity were used; namely, a homogeneous water phantom and phantoms
      made of polymethyl methacrylate slabs containing different-sized, low- and high
      density inserts of heterogeneous materials. Electron beams with 8 and 15 MeV
      nominal energy generated by an Elekta Synergy linear accelerator were
      investigated. Measurements were performed for a 10 cm * 10 cm applicator at a
      source-to-surface distance of 100 cm. Individual parts of the beam-defining
      system were introduced into the simulation one at a time in order to show their
      effect on depth doses. In contrast to the first scattering foil, the secondary
      scattering foil, X and Y jaws and applicator provide up to 5% of the dose. A 2%/2
      mm agreement between MCNP and measurements was found in the homogenous phantom,
      and in the presence of heterogeneities in the range of 1-3%, being generally
      within 2% of the measurements for both energies in a "complex" phantom. A full
      component simulation is necessary in order to obtain a realistic model of the
      beam. The MCNP4C results agree well with the measured electron dose
      distributions.

PMID- 23533163
TI  - Headache and physical and sexual abuse among Jewish and Arab adolescents in
      Israel.
AB  - The purpose of the present study was to evaluate the relationship between
      headaches and physical and sexual abuse. A self-administered, anonymous
      questionnaire was presented to 2088 tenth grade students in Northern Israel.
      Participants were Jews and Arabs between the ages of 15 to 16 years. Arab
      adolescents comprised 55% of the analyzed sample and adolescent Jews 45%. With
      regard to gender, 56% of participants were females. Of the Arab participants,
      18.6% reported having frequent headaches, less than that reported in the Jewish
      group (27.9%). Jewish girls who were physically abused during childhood had a
      higher prevalence of frequent headaches (55% vs 33% P < .001). Jewish students
      who reported being sexually abused had higher headache prevalence as well (44.4%
      vs 27.3% P = .05). In conclusion, adolescents who reported to have been
      physically or sexually abused report a higher prevalence of headache compared to
      their peers.

PMID- 23533164
TI  - Prospective Open-Label, Single-Arm, Multicenter, Safety, Tolerability, and
      Pharmacokinetic Studies of Intravenous Levetiracetam in Children With Epilepsy.
AB  - Levetiracetam given via intravenous administration has been shown to be an
      effective alternative in adults with epilepsy when oral administration is not
      feasible. This study was a prospective single-arm, multicenter study to assess
      tolerability, safety, and pharmacokinetics of intravenous levetiracetam in
      children with epilepsy. Children with epilepsy ages 1 month to 16 years requiring
      intravenous levetiracetam were enrolled. Assessments included vital signs,
      electrocardiogram, hematology, chemistry, plasma concentrations of antiepileptic
      medications, weight, physical/neurological examinations, and pharmacokinetics. A
      total of 52 patients were enrolled. Mild to moderate treatment-emergent adverse
      events occurred in 63%, the most frequent being pyrexia and dry mouth. Most other
      treatment-emergent adverse events were considered unrelated to intravenous
      levetiracetam administration. Therefore, intravenous levetiracetam in the acute
      setting was overall well tolerated in children 1 month to 16 years.

PMID- 23533165
TI  - Novel STXBP1 mutations in 2 patients with early infantile epileptic
      encephalopathy.
AB  - The authors describe 2 patients with early infantile epileptic encephalopathy
      caused by 2 novel mutations involving the STXBP1 gene. The authors suggest that
      in spite of the rarity of STXBP1 mutations, molecular analysis of STXBP1 gene
      should be performed in patients with early infantile epileptic encephalopathy,
      after exclusion of ARX mutations in male patients and CDKL5 mutations in female
      patients. The potential mechanisms explaining the variable clinical phenotypes
      caused by STXBP1 mutations are discussed and the designation of early-onset
      epileptic encephalopathies, including an updated genetic classification, is
      proposed to encompass the epileptic encephalopathies beginning in the first 6
      months of life. 

PMID- 23533166
TI  - In vitro and in vivo degradation behavior of n-HA/PCL-Pluronic-PCL polyurethane
      composites.
AB  - Scaffolds for bone tissue engineering applications should have suitable
      degradability in favor of new bone ingrowth after implantation into bone defects.
      In this study, degradation behavior of polyurethane composites composed of
      triblock copolymer poly(caprolactone)-poluronic-poly(caprolactone) (PCL-Pluronic
      PCL, PCFC) and nanohydroxyapatite (n-HA) was investigated. The water contact
      angle and water absorption were measured to reveal the effect of n-HA content on
      the surface wettability and swelling behavior of the n-HA/PCFC composites,
      respectively. The weight loss in three degradation media with pH value of 4.0,
      7.4, and 9.18 was also studied accordingly. Fourier transform infrared analysis,
      differential scanning calorimeter, X-ray diffraction, thermal-gravimetric
      analysis, and scanning electron microscopy were used to investigate the change of
      chemical structure and micromorphology after the n-HA/PCFC composite with 30% HA
      was degraded for different time intervals. Meanwhile, in vivo degradation was
      conducted by subcutaneous implantation. The weight loss and morphology change
      during observation periods were also studied.

PMID- 23533167
TI  - Methylation of the PTPRO gene in human hepatocellular carcinoma and
      identification of VCP as its substrate.
AB  - We have previously reported that the gene encoding protein tyrosine phosphatase
      receptor type-O (PTPRO) is suppressed by promoter methylation in a rat model of
      hepatocellular carcinoma (HCC) and it functions as tumor suppressor in leukemia
      and lung cancer. Here, we explored the methylation and expression of PTPRO as
      well as its function in human HCC. MassARRAY analysis of primary human HCC and
      matching liver samples (n = 24) revealed significantly higher (P = 0.004)
      methylation density at the promoter CGI in tumors. Combined bisulfite restriction
      analysis (COBRA) of another set of human HCC samples (n = 17) demonstrated that
      the CGI was methylated in 29% of tumors where expression of PTPRO was lower than
      that in corresponding matching livers. A substrate-trapping mutant of PTPRO that
      stabilizes the bound substrates was used to identify its novel substrate(s).
      VCP/p97 was found to be a PTPRO substrate by mass spectrometry of the peptides
      pulled down by the substrate-trapping mutant of PTPRO. Tyrosyl dephosphorylation
      of VCP following ectopic expression of wild-type PTPRO in H293T and HepG2 cells
      confirmed that it is a bona fide substrate of PTPRO. Treatment of PTPRO
      overexpressing HepG2 cells with Doxorubicin, a DNA damaging drug commonly used in
      therapy of primary HCC, sensitized these cells to this potent anticancer drug
      that correlated with dephosphorylation of VCP. Taken together, these results
      demonstrate methylation and downregulation of PTPRO in a subset of primary human
      HCC and establish VCP as a novel functionally important substrate of this
      tyrosine phosphatase that could be a potential molecular target for HCC therapy.

PMID- 23533168
TI  - NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells.
AB  - Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by
      overexpression of a defined set of transcription factors requires epigenetic
      changes in pluripotency genes. Nuclear reprogramming is an inefficient process
      and the molecular mechanisms that reset the epigenetic state during iPSC
      generation are largely unknown. Here, we show that downregulation of the
      nucleosome remodeling and deacetylation (NuRD) complex is required for efficient
      reprogramming. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of
      iPSCs by establishing heterochromatic features and silencing embryonic stem cell
      specific marker genes, including Oct4 and Nanog. Depletion of Mbd3, on the other
      hand, improves reprogramming efficiency and facilitates the formation of
      pluripotent stem cells that are capable of generating viable chimeric mice, even
      in the absence of c-Myc or Sox2. The results establish Mbd3/NuRD as an important
      epigenetic regulator that restricts the expression of key pluripotency genes,
      suggesting that drug-induced downregulation of Mbd3/NuRD may be a powerful means
      to improve the efficiency and fidelity of reprogramming.

PMID- 23533169
TI  - Hydroxyapatite-coated magnesium implants with improved in vitro and in vivo
      biocorrosion, biocompatibility, and bone response.
AB  - Magnesium and its alloys are candidate materials for biodegradable implants;
      however, excessively rapid corrosion behavior restricts their practical uses in
      biological systems. For such applications, surface modification is essential, and
      the use of anticorrosion coatings is considered as a promising avenue. In this
      study, we coated Mg with hydroxyapatite (HA) in an aqueous solution containing
      calcium and phosphate sources to improve its in vitro and in vivo biocorrosion
      resistance, biocompatibility and bone response. A layer of needle-shaped HA
      crystals was created uniformly on the Mg substrate even when the Mg sample had a
      complex shape of a screw. In addition, a dense HA-stratum between this layer and
      the Mg substrate was formed. This HA-coating layer remarkably reduced the
      corrosion rate of the Mg tested in a simulated body fluid. Moreover, the
      biological response, including cell attachment, proliferation and
      differentiation, of the HA-coated samples was enhanced considerably compared to
      samples without a coating layer. The preliminary in vivo experiments also showed
      that the biocorrosion of the Mg implant was significantly retarded by HA coating,
      which resulted in good mechanical stability. In addition, in the case of the HA
      coated implants, biodegradation was mitigated, particularly over the first 6
      weeks of implantation. This considerably promoted bone growth at the interface
      between the implant and bone. These results confirmed that HA-coated Mg is a
      promising material for biomedical implant applications.

PMID- 23533170
TI  - Brassinosteroid signalling.
AB  - The brassinosteroid (BR) class of steroid hormones regulates plant development
      and physiology. The BR signal is transduced by a receptor kinase-mediated signal
      transduction pathway, which is distinct from animal steroid signalling systems.
      Recent studies have fully connected the BR signal transduction chain and have
      identified thousands of BR target genes, linking BR signalling to numerous
      cellular processes. Molecular links between BR and several other signalling
      pathways have also been identified. Here, we provide an overview of the highly
      integrated BR signalling network and explain how this steroid hormone functions
      as a master regulator of plant growth, development and metabolism.

PMID- 23533172
TI  - UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell
      survival and development.
AB  - Multi-organ animals, such as vertebrates, require the development of a closed
      vascular system to ensure the delivery of nutrients to, and the transport of
      waste from, their organs. As a result, an organized vascular network that is
      optimal for tissue perfusion is created through not only the generation of new
      blood vessels but also the remodeling and maintenance of endothelial cells via
      apoptotic and cell survival pathways. Here, we show that UBIAD1, a vitamin
      K2/menaquinone-4 biosynthetic enzyme, functions cell-autonomously to regulate
      endothelial cell survival and maintain vascular homeostasis. From a recent
      vascular transgene-assisted zebrafish forward genetic screen, we have identified
      a ubiad1 mutant, reddish/reh, which exhibits cardiac edema as well as cranial
      hemorrhages and vascular degeneration owing to defects in endothelial cell
      survival. These findings are further bolstered by the expression of UBIAD1 in
      human umbilical vein endothelial cells and human heart tissue, as well as the
      rescue of the reh cardiac and vascular phenotypes with either zebrafish or human
      UBIAD1. Furthermore, we have discovered that vitamin K2, which is synthesized by
      UBIAD1, can also rescue the reh vascular phenotype but not the reh cardiac
      phenotype. Additionally, warfarin-treated zebrafish, which have decreased active
      vitamin K, display similar vascular degeneration as reh mutants, but exhibit
      normal cardiac function. Overall, these findings reveal an essential role for
      UBIAD1-generated vitamin K2 to maintain endothelial cell survival and overall
      vascular homeostasis; however, an alternative UBIAD1/vitamin K-independent
      pathway may regulate cardiac function.

PMID- 23533171
TI  - Morphogen transport.
AB  - The graded distribution of morphogens underlies many of the tissue patterns that
      form during development. How morphogens disperse from a localized source and how
      gradients in the target tissue form has been under debate for decades. Recent
      imaging studies and biophysical measurements have provided evidence for various
      morphogen transport models ranging from passive mechanisms, such as free or
      hindered extracellular diffusion, to cell-based dispersal by transcytosis or
      cytonemes. Here, we analyze these transport models using the morphogens Nodal,
      fibroblast growth factor and Decapentaplegic as case studies. We propose that
      most of the available data support the idea that morphogen gradients form by
      diffusion that is hindered by tortuosity and binding to extracellular molecules.

PMID- 23533173
TI  - Dll4-Notch signaling determines the formation of native arterial collateral
      networks and arterial function in mouse ischemia models.
AB  - Arteriogenesis requires growth of pre-existing arteriolar collateral networks and
      determines clinical outcome in arterial occlusive diseases. Factors responsible
      for the development of arteriolar collateral networks are poorly understood. The
      Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts
      vessel branching. We hypothesized that Dll4 may act as a genetic determinant of
      collateral arterial networks and functional recovery in stroke and hind limb
      ischemia models in mice. Genetic loss- and gain-of-function approaches in mice
      showed that Dll4-Notch signaling restricts pial collateral artery formation by
      modulating arterial branching morphogenesis during embryogenesis. Adult Dll4(+/-)
      mice showed increased pial collateral numbers, but stroke volume upon middle
      cerebral artery occlusion was not reduced compared with wild-type littermates.
      Likewise, Dll4(+/-) mice showed reduced blood flow conductance after femoral
      artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia
      was more severe. In peripheral arteries, loss of Dll4 adversely affected
      excitation-contraction coupling in arterial smooth muscle in response to
      vasopressor agents and arterial vessel wall adaption in response to increases in
      blood flow, collectively contributing to reduced flow reserve. We conclude that
      Dll4-Notch signaling modulates native collateral formation by acting on vascular
      branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue
      perfusion by acting on arterial function and structure. Loss of Dll4 stimulates
      collateral formation and angiogenesis, but in the context of ischemic diseases
      such beneficial effects are overruled by adverse functional changes,
      demonstrating that ischemic recovery is not solely determined by collateral
      number but rather by vessel functionality.

PMID- 23533175
TI  - Lgr4-mediated Wnt/beta-catenin signaling in peritubular myoid cells is essential
      for spermatogenesis.
AB  - Peritubular myoid cells (PMCs) are myofibroblast-like cells that surround the
      seminiferous tubules and play essential roles in male fertility. How these cells
      modulate spermatogenesis and the signaling pathways that are involved are largely
      unknown. Here we report that Lgr4 is selectively expressed in mouse PMCs in the
      testes, and loss of Lgr4 leads to germ cells arresting at meiosis I and then
      undergoing apoptosis. In PMCs of Lgr4 mutant mice, the expression of androgen
      receptor, alpha-smooth muscle actin and extracellular matrix proteins was
      dramatically reduced. Malfunctioning PMCs further affected Sertoli cell nuclear
      localization and functional protein expression in Lgr4(-/-) mice. In addition,
      Wnt/beta-catenin signaling was activated in wild-type PMCs but attenuated in
      those of Lgr4(-/-) mice. When Wnt/beta-catenin signaling was reactivated by
      crossing with Apc(min/+) mice or by Gsk3beta inhibitor treatment, the Lgr4
      deficiency phenotype in testis was partially rescued. Together, these data
      demonstrate that Lgr4 signaling through Wnt/beta-catenin regulates PMCs and is
      essential for spermatogenesis.

PMID- 23533174
TI  - The transition from differentiation to growth during dermomyotome-derived
      myogenesis depends on temporally restricted hedgehog signaling.
AB  - The development of a functional tissue requires coordination of the amplification
      of progenitors and their differentiation into specific cell types. The molecular
      basis for this coordination during myotome ontogeny is not well understood.
      Dermomytome progenitors that colonize the myotome first acquire myocyte identity
      and subsequently proliferate as Pax7-expressing progenitors before undergoing
      terminal differentiation. We show that the dynamics of sonic hedgehog (Shh)
      signaling is crucial for this transition in both avian and mouse embryos.
      Initially, Shh ligand emanating from notochord/floor plate reaches the
      dermomyotome, where it both maintains the proliferation of dermomyotome cells and
      promotes myogenic differentiation of progenitors that colonized the myotome.
      Interfering with Shh signaling at this stage produces small myotomes and
      accumulation of Pax7-expressing progenitors. An in vivo reporter of Shh activity
      combined with mouse genetics revealed the existence of both activator and
      repressor Shh activities operating on distinct subsets of cells during the
      epaxial myotomal maturation. In contrast to observations in mice, in avians Shh
      promotes the differentiation of both epaxial and hypaxial myotome domains.
      Subsequently, myogenic progenitors become refractory to Shh; this is likely to
      occur at the level of, or upstream of, smoothened signaling. The end of
      responsiveness to Shh coincides with, and is thus likely to enable, the
      transition into the growth phase of the myotome.

PMID- 23533176
TI  - Specification of posterior hypothalamic neurons requires coordinated activities
      of Fezf2, Otp, Sim1a and Foxb1.2.
AB  - The hypothalamus is a key integrative center in the brain that consists of
      diverse cell types required for a variety of functions including homeostasis,
      reproduction, stress response, social and cognitive behavior. Despite our
      knowledge of several transcription factors crucial for hypothalamic development,
      it is not known how the wide diversity of neuron types in the hypothalamus is
      produced. In particular, almost nothing is known about the mechanisms that
      specify neurons in the posteriormost part of the hypothalamus, the mammillary
      area. Here, we investigated the specification of two distinct neuron types in the
      mammillary area that produce the hypothalamic hormones Vasoactive intestinal
      peptide (Vip) and Urotensin 1 (Uts1). We show that Vip- and Uts1-positive neurons
      develop in distinct domains in the mammillary area defined by the differential
      expression of the transcription factors Fezf2, Otp, Sim1a and Foxb1.2.
      Coordinated activities of these factors are crucial for the establishment of the
      mammillary area subdomains and the specification of Vip- and Uts1-positive
      neurons. In addition, Fezf2 is important for early development of the posterior
      hypothalamus. Thus, our study provides the first molecular anatomical map of the
      posterior hypothalamus in zebrafish and identifies, for the first time, molecular
      requirements underlying the specification of distinct posterior hypothalamic
      neuron types.

PMID- 23533177
TI  - Lis1 mediates planar polarity of auditory hair cells through regulation of
      microtubule organization.
AB  - The V-shaped hair bundles atop auditory hair cells and their uniform orientation
      are manifestations of epithelial planar cell polarity (PCP) required for proper
      perception of sound. PCP is regulated at the tissue level by a conserved core
      Wnt/PCP pathway. However, the hair cell-intrinsic polarity machinery is poorly
      understood. Recent findings implicate hair cell microtubules in planar
      polarization of hair cells. To elucidate the microtubule-mediated polarity
      pathway, we analyzed Lis1 function in the auditory sensory epithelium in the
      mouse. We show that conditional deletion of Lis1 in developing hair cells causes
      defects in cytoplasmic dynein and microtubule organization, resulting in planar
      polarity defects without overt effects on the core PCP pathway. Lis1 ablation
      during embryonic development results in defects in hair bundle morphology and
      orientation, cellular organization and junctional nectin localization. We present
      evidence that Lis1 regulates localized Rac-PAK signaling in embryonic hair cells,
      probably through microtubule-associated Tiam1, a guanine nucleotide exchange
      factor for Rac. Lis1 ablation in postnatal hair cells significantly disrupts
      centrosome anchoring and the normal V-shape of hair bundles, accompanied by
      defects in the pericentriolar matrix and microtubule organization. Lis1 is also
      required for proper positioning of the Golgi complex and mitochondria as well as
      for hair cell survival. Together, our results demonstrate that Lis1 mediates the
      planar polarity of hair cells through regulation of microtubule organization
      downstream of the tissue polarity pathway.

PMID- 23533178
TI  - Notch and Nodal control forkhead factor expression in the specification of
      multipotent progenitors in sea urchin.
AB  - Indirect development, in which embryogenesis gives rise to a larval form,
      requires that some cells retain developmental potency until they contribute to
      the different tissues in the adult, including the germ line, in a later, post
      embryonic phase. In sea urchins, the coelomic pouches are the major contributor
      to the adult, but how coelomic pouch cells (CPCs) are specified during
      embryogenesis is unknown. Here we identify the key signaling inputs into the CPC
      specification network and show that the forkhead factor foxY is the first
      transcription factor specifically expressed in CPC progenitors. Through
      dissection of its cis-regulatory apparatus we determine that the foxY expression
      pattern is the result of two signaling inputs: first, Delta/Notch signaling
      activates foxY in CPC progenitors; second, Nodal signaling restricts its
      expression to the left side, where the adult rudiment will form, through direct
      repression by the Nodal target pitx2. A third signal, Hedgehog, is required for
      coelomic pouch morphogenesis and institution of laterality, but does not directly
      affect foxY transcription. Knockdown of foxY results in a failure to form
      coelomic pouches and disrupts the expression of virtually all transcription
      factors known to be expressed in this cell type. Our experiments place foxY at
      the top of the regulatory hierarchy underlying the specification of a cell type
      that maintains developmental potency.

PMID- 23533179
TI  - Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/beta
      catenin-dependent cell fate decisions during vertebrate development.
AB  - Using zebrafish, we have characterised the function of Protein tyrosine kinase 7
      (Ptk7), a transmembrane pseudokinase implicated in Wnt signal transduction during
      embryonic development and in cancer. Ptk7 is a known regulator of mammalian
      neural tube closure and Xenopus convergent extension movement. However,
      conflicting reports have indicated both positive and negative roles for Ptk7 in
      canonical Wnt/beta-catenin signalling. To clarify the function of Ptk7 in
      vertebrate embryonic patterning and morphogenesis, we generated maternal-zygotic
      (MZ) ptk7 mutant zebrafish using a zinc-finger nuclease (ZFN) gene targeting
      approach. Early loss of zebrafish Ptk7 leads to defects in axial convergence and
      extension, neural tube morphogenesis and loss of planar cell polarity (PCP).
      Furthermore, during late gastrula and segmentation stages, we observe significant
      upregulation of beta-catenin target gene expression and demonstrate a clear role
      for Ptk7 in attenuating canonical Wnt/beta-catenin activity in vivo. MZptk7
      mutants display expanded differentiation of paraxial mesoderm within the tailbud,
      suggesting an important role for Ptk7 in regulating canonical Wnt-dependent fate
      specification within posterior stem cell pools post-gastrulation. Furthermore, we
      demonstrate that a plasma membrane-tethered Ptk7 extracellular fragment is
      sufficient to rescue both PCP morphogenesis and Wnt/beta-catenin patterning
      defects in MZptk7 mutant embryos. Our results indicate that the extracellular
      domain of Ptk7 acts as an important regulator of both non-canonical Wnt/PCP and
      canonical Wnt/beta-catenin signalling in multiple vertebrate developmental
      contexts, with important implications for the upregulated PTK7 expression
      observed in human cancers.

PMID- 23533181
TI  - Neuroblast pattern and identity in the Drosophila tail region and role of
      doublesex in the survival of sex-specific precursors.
AB  - The central nervous system is composed of segmental units (neuromeres), the size
      and complexity of which evolved in correspondence to their functional
      requirements. In Drosophila, neuromeres develop from populations of neural stem
      cells (neuroblasts) that delaminate from the early embryonic neuroectoderm in a
      stereotyped spatial and temporal pattern. Pattern units closely resemble the
      ground state and are rather invariant in thoracic (T1-T3) and anterior abdominal
      (A1-A7) segments of the embryonic ventral nerve cord. Here, we provide a
      comprehensive neuroblast map of the terminal abdominal neuromeres A8-A10, which
      exhibit a progressively derived character. Compared with thoracic and anterior
      abdominal segments, neuroblast numbers are reduced by 28% in A9 and 66% in A10
      and are almost entirely absent in the posterior compartments of these segments.
      However, all neuroblasts formed exhibit serial homology to their counterparts in
      more anterior segments and are individually identifiable based on their
      combinatorial code of marker gene expression, position, delamination time point
      and the presence of characteristic progeny cells. Furthermore, we traced the
      embryonic origin and characterised the postembryonic lineages of a set of
      terminal neuroblasts, which have been previously reported to exhibit sex-specific
      proliferation behaviour during postembryonic development. We show that the
      respective sex-specific product of the gene doublesex promotes programmed cell
      death of these neuroblasts in females, and is needed for their survival, but not
      proliferation, in males. These data establish the terminal neuromeres as a model
      for further investigations into the mechanisms controlling segment- and sex
      specific patterning in the central nervous system.

PMID- 23533180
TI  - A role for Vg1/Nodal signaling in specification of the intermediate mesoderm.
AB  - The intermediate mesoderm (IM) is the embryonic source of all kidney tissue in
      vertebrates. The factors that regulate the formation of the IM are not yet well
      understood. Through investigations in the chick embryo, the current study
      identifies and characterizes Vg1/Nodal signaling (henceforth referred to as
      'Nodal-like signaling') as a novel regulator of IM formation. Excess Nodal-like
      signaling at gastrulation stages resulted in expansion of the IM at the expense
      of the adjacent paraxial mesoderm, whereas inhibition of Nodal-like signaling
      caused repression of IM gene expression. IM formation was sensitive to levels of
      the Nodal-like pathway co-receptor Cripto and was inhibited by a truncated form
      of the secreted molecule cerberus, which specifically blocks Nodal, indicating
      that the observed effects are specific to the Nodal-like branch of the TGFbeta
      signaling pathway. The IM-promoting effects of Nodal-like signaling were distinct
      from the known effects of this pathway on mesoderm formation and left-right
      patterning, a finding that can be attributed to specific time windows for the
      activities of these Nodal-like functions. Finally, a link was observed between
      Nodal-like and BMP signaling in the induction of IM. Activation of IM genes by
      Nodal-like signaling required an active BMP signaling pathway, and Nodal-like
      signals induced phosphorylation of Smad1/5/8, which is normally associated with
      activation of BMP signaling pathways. We postulate that Nodal-like signaling
      regulates IM formation by modulating the IM-inducing effects of BMP signaling.

PMID- 23533182
TI  - Native adipose stromal cells egress from adipose tissue in vivo: evidence during
      lymph node activation.
AB  - Adipose tissue (AT) has become accepted as a source of multipotent progenitor
      cells, the adipose stromal cells (ASCs). In this regard, considerable work has
      been performed to harvest and characterize this cell population as well as to
      investigate the mechanisms by which transplanted ASCs mediate tissue
      regeneration. In contrast the endogenous release of native ASCs by AT has been
      poorly investigated. In this work, we show that native ASCs egress from murine
      AT. Indeed, we demonstrated that the release of native ASCs from AT can be
      evidenced both using an ex vivo perfusion model that we set up and in vivo. Such
      a mobilization process is controlled by CXCR4 chemokine receptor. In addition,
      once mobilized from AT, circulating ASCs were found to navigate through lymph
      fluid and to home into lymph nodes (LN). Therefore, we demonstrated that, during
      the LN activation, the fat depot encapsulating the activated LN releases native
      ASCs, which in turn invade the activated LN. Moreover, the ASCs invading the LN
      were visualized in close physical interaction with podoplanin and ER-TR7 positive
      structures corresponding to the stromal network composing the LN. This dynamic
      was impaired with CXCR4 neutralizing antibody. Taken together, these data provide
      robust evidences that native ASCs can traffic in vivo and that AT might provide
      stromal cells to activated LNs.

PMID- 23533183
TI  - Type I interferon receptor deficiency prevents murine Sjogren's syndrome.
AB  - In Sjogren's Syndrome (SS), inherent glandular defects, autoimmunity, and
      mononuclear cell infiltration within the salivary glands cause reduced salivation
      leading to xerostomia. Excessive production of type I interferons (IFN),
      triggered by environmental and genetic factors, is considered pathogenic in this
      disorder. However, whether type I IFN production is causative or an outcome of
      the disease process is not known. To address this question, we introduced a
      deficiency of interferon alpha receptor 1 (Ifnar1) into B6.Aec1Aec2 mice, which
      are known to have the genetic loci necessary for developing a SS-like disorder.
      This new mouse strain, B6.Aec1Aec2Ifnar1 (-/-), lacking type I IFN-mediated
      signaling, was characterized for pilocarpine-induced salivation, the presence of
      serum autoantibodies, sialoadenitis, and dacryoadenitis. Compared with the
      B6.Aec1Aec2Ifnar1 (+/+) (wild-type) mice, the B6.Aec1Aec2Ifnar1 (-/-) (knockout)
      mice had significantly lower mononuclear cell infiltration in the salivary and
      lacrimal glands. The knockout mice were completely protected from salivary gland
      dysfunction. Surprisingly, they had a robust autoantibody response comparable
      with that of the wild-type mice. These findings demonstrate that, in the absence
      of type I IFN-mediated signaling, systemic autoantibody responses can be
      dissociated from glandular pathology. Our study suggests that, in genetically
      susceptible individuals, the type I IFN pathway can instigate certain features of
      SS.

PMID- 23533184
TI  - Dexamethasone released from cochlear implant coatings combined with a protein
      repellent hydrogel layer inhibits fibroblast proliferation.
AB  - The insertion of cochlear implants into the inner ear often causes inflammation
      and fibrosis inside the scala tympani and thus growth of fibrous tissue on the
      implant surface. This deposition leads to the loss of function in both electrical
      and laser-based implants. The design of this study was to realize fibroblast
      growth inhibition by dexamethasone (Dex) released from the base material of the
      implant [polydimethylsiloxane (PDMS)]. To prevent cell and protein adhesion, the
      PDMS was coated with a hydrogel layer [star-shaped polyethylene glycol prepolymer
      (sPEG)]. Drug release rates were studied over 3 months, and surface
      characterization was performed. It was observed that the hydrogel slightly
      smoothened the surface roughened by the Dex crystals. The hydrogel coating
      reduced and prolonged the release of the drug over several months. Unmodified,
      sPEG-coated, Dex-loaded, and Dex/sPEG-equipped PDMS filaments were cocultivated
      in vitro with fluorescent fibroblasts, analyzed by fluorescent microscopy, and
      quantified by cell counting. Compared to the unmodified PDMS, cell growth on all
      modified filaments was averagely 95% +/-standard deviation (SD) less, while cell
      growth on the bottom of the culture dishes containing Dex-loaded filaments was
      reduced by 70% +/-SD. Both, Dex and sPEG prevented direct cell growth on the
      filament surfaces, while drug delivery was maintained for the duration of several
      months.

PMID- 23533185
TI  - Gonad differentiation and puberty onset in the zebrafish: evidence for the
      dependence of puberty onset on body growth but not age in females.
AB  - Puberty is the period in the vertebrate life cycle that marks the transition from
      sexual immaturity to maturity, enabling an animal to acquire adult reproductive
      functions. Puberty, an important point in vertebrate reproductive life, has been
      under extensive study in the past decades. It has been known for a long time that
      the initiation of puberty in mammals is closely associated with body growth and
      metabolism; however, there has been no equivalent report in small model teleosts
      such as the zebrafish. Using morphological and histological analysis, this study
      was undertaken to examine the timing of gonad differentiation and female
      maturation (puberty) in the zebrafish, with particular emphasis on the potential
      impact of body growth on the onset of puberty. Our data showed that gonad
      differentiation in the zebrafish completed around 35 days post-fertilization
      (dpf) in females and 45 dpf in males. Puberty in females is initiated at around
      45 dpf. Our experiments provided clear evidence that the initiation of puberty in
      female zebrafish was strongly correlated with body size but not age, supporting
      the importance of the growth axis in the onset of puberty. This study provides
      essential information on basic characteristics of growth and reproduction in
      zebrafish.

PMID- 23533186
TI  - Differential left ventricular remodelling and longitudinal function distinguishes
      low flow from normal-flow preserved ejection fraction low-gradient severe aortic
      stenosis.
AB  - AIMS: There is uncertainty in identifying patients with severe aortic stenosis
      (AS) with preserved left ventricular (LV) ejection fraction, low flow, and low
      gradients (LFLG). Prior studies propose that these patients demonstrate
      significant concentric remodelling and decreased survival, while others suggest
      that they have features and survival similar to moderate AS. METHODS AND RESULTS:
      We compared the clinical characteristics, echocardiographic features, and overall
      survival of LFLG AS patients (n = 38) to those with normal-flow, low-gradient
      (NFLG) severe AS (n = 75) and moderate AS (n = 70). Low-flow, low-gradient
      patients had the lowest end-diastolic volume index (43 vs. 54 vs. 54 mL/m2, P <
      0.001), highest relative wall thickness (RWT) (60 vs. 49 vs. 48%, P < 0.001), and
      lowest septal mitral annular displacement (1.0 vs. 1.5 vs. 1.5 cm, P < 0.001).
      New York Heart Association (NYHA) class III/IV symptoms were the most frequent in
      the LFLG group (29 vs. 11 vs. 3%, P < 0.001). Survival at 3 years was
      significantly lower in LFLG compared with NFLG (P = 0.006) and moderate AS (P =
      0.002), but not different between NFLG and moderate AS (P = 0.49). Higher NYHA
      classification (HR 1.77, 95% CI 1.22-2.57), RWT > 50% (HR 3.28, 95% CI 1.33-8.1),
      and septal displacement <1.1 cm (HR 3.93, 95% CI 1.96-7.82) but not low flow were
      independent predictors of survival in Cox proportional hazards analysis.
      CONCLUSION: Preserved ejection fraction, LFLG AS patients exhibit marked
      concentric remodelling and impaired longitudinal functional-features that predict
      their poor long-term survival. Normal-flow, low-gradient AS patients have
      outcomes similar to moderate AS.

PMID- 23533187
TI  - Natriuretic peptide receptor A signaling regulates stem cell recruitment and
      angiogenesis: a model to study linkage between inflammation and tumorigenesis.
AB  - Natriuretic peptide receptor A (NPRA), the signaling receptor for the cardiac
      hormone, atrial natriuretic peptide (ANP), is expressed abundantly in
      inflamed/injured tissues and tumors. NPRA deficiency substantially decreases
      tissue inflammation and inhibits tumor growth. However, the precise mechanism of
      NPRA function and whether it links inflammation and tumorigenesis remains
      unknown. Since both injury repair and tumor growth require stem cell recruitment
      and angiogenesis, we examined the role of NPRA signaling in tumor angiogenesis as
      a model of tissue injury repair in this study. In in vitro cultures, aortas from
      NPRA-KO mice show significantly lower angiogenic response compared to wild-type
      counterparts. The NPRA antagonist that decreases NPRA expression, inhibits
      lipopolysaccharide-induced angiogenesis. The reduction in angiogenesis correlates
      with decreased expression of vascular endothelial growth factor and chemokine (C
      X-C motif) receptor 4 (CXCR4) implicating a cell recruitment defect. To test
      whether NPRA regulates migration of cells to tumors, mesenchymal stem cells
      (MSCs) were administered i.v., and the results showed that MSCs fail to migrate
      to the tumor microenvironment in NPRA-KO mice. However, coimplanting tumor cells
      with MSCs increases angiogenesis and tumorigenesis in NPRA-KO mice, in part by
      promoting expression of CXCR4 and its ligand, stromal cell-derived factor 1alpha.
      Taken together, these results demonstrate that NPRA signaling regulates stem cell
      recruitment and angiogenesis leading to tumor growth. Thus, NPRA signaling
      provides a key linkage between inflammation and tumorigenesis, and NPRA may be a
      target for drug development against cancers and tissue injury repair.

PMID- 23533188
TI  - Association between maternal serum 25-hydroxyvitamin D level and pregnancy and
      neonatal outcomes: systematic review and meta-analysis of observational studies.
AB  - OBJECTIVE: To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on
      pregnancy outcomes and birth variables. DESIGN: Systematic review and meta
      analysis. DATA SOURCES: Medline (1966 to August 2012), PubMed (2008 to August
      2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane
      database of systematic reviews, and the Cochrane database of registered clinical
      trials. STUDY SELECTION: Studies reporting on the association between serum 25
      OHD levels during pregnancy and the outcomes of interest (pre-eclampsia,
      gestational diabetes, bacterial vaginosis, caesarean section, small for
      gestational age infants, birth weight, birth length, and head circumference).
      DATA EXTRACTION: Two authors independently extracted data from original research
      articles, including key indicators of study quality. We pooled the most adjusted
      odds ratios and weighted mean differences. Associations were tested in subgroups
      representing different patient characteristics and study quality. RESULTS: 3357
      studies were identified and reviewed for eligibility. 31 eligible studies were
      included in the final analysis. Insufficient serum levels of 25-OHD were
      associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence
      interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for
      gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25
      OHD levels had an increased risk of bacterial vaginosis and low birthweight
      infants but not delivery by caesarean section. CONCLUSION: Vitamin D
      insufficiency is associated with an increased risk of gestational diabetes, pre
      eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD
      levels had an increased risk of bacterial vaginosis and lower birth weight
      infants, but not delivery by caesarean section.

PMID- 23533189
TI  - Vitamin D sufficiency in pregnancy.

PMID- 23533190
TI  - Will 1 April mark the beginning of the end of England's NHS? Yes.

PMID- 23533191
TI  - Will 1 April mark the beginning of the end of England's NHS? No.

PMID- 23533192
TI  - What should clinical commissioning groups do on 1 April 2013?

PMID- 23533193
TI  - NICE recommends training programmes for parents to tackle children's antisocial
      behaviour.

PMID- 23533194
TI  - Infrared spectroscopic characterization of carbonated apatite: a combined
      experimental and computational study.
AB  - A combined experimental and computational approach was employed to investigate
      the feasibility and effectiveness of characterizing carbonated apatite (CAp) by
      infrared (IR) spectroscopy. First, an experimental comparative study was
      conducted to identify characteristic IR vibrational bands of carbonate
      substitution in the apatite lattice. The IR spectra of pure hydroxyapatite (HA),
      carbonate adsorbed on the HA surface, a physical mixture of HA and sodium
      carbonate monohydrate, a physical mixture of HA and calcite, synthetic CAps
      prepared using three methods (precipitation method, hydrothermal route, and solid
      gas reaction at high temperature) and biological apatites (human enamel, human
      cortical bone, and two animal bones) were compared. Then, the IR vibrational
      bands of carbonate in CAp were calculated with density functional theory. The
      experimental study identified characteristic IR bands of carbonate that cannot be
      generated from surface adsorption or physical mixtures and the results show that
      the bands at ~880, 1413, and 1450 cm(-1) should not be used as characteristic
      bands of CAp since they could result from carbonate adsorbed on the apatite
      crystals surface or present as a separate phase. The combined experimental and
      computational study reveals that the carbonate v3 bands at ~1546 and 1465 cm(-1)
      are, respectively, the IR signature bands for type A CAp and type B CAp.

PMID- 23533196
TI  - Preparation, characterization, and biological properties of organic-inorganic
      nanocomposite coatings on titanium substrates prepared by sol-gel.
AB  - When surface-reactive (bioactive) coatings are applied to medical implants by
      means of the sol-gel dip-coating technique, the biological proprieties of the
      surface of the implant can be locally modified to match the properties of the
      surrounding tissues to provide a firm fixation of the implant. The aim of this
      study has been to synthesize, via sol-gel, organoinorganic nanoporous materials
      and to dip-coat a substrate to use in dental applications. Different systems have
      been prepared consisting of an inorganic zirconium-based matrix, in which a
      biodegradable polymer, the poly-epsilon-caprolactone was incorporated in
      different percentages. The materials synthesized by the sol-gel process, before
      gelation, when they were still in sol phase, have been used to coat a titanium
      grade 4 (Ti-4) substrate to change its surface biological properties. Thin films
      have been obtained by means of the dip-coating technique. A microstructural
      analysis of the obtained coatings was performed using scanning electron
      microscopy (SEM) and Fourier transform infrared spectroscopy. The biological
      proprieties have been investigated by means of tests in vitro. The bone-bonding
      capability of the nanocomposite films has been evaluated by examining the
      appearance of apatite on their surface when plunged in a simulated body fluid
      (SBF) with ion concentrations nearly equal to those of human blood plasma. The
      examination of apatite formation on the nanocomposites, after immersion in SBF,
      has been carried out by SEM equipped with energy-dispersive X-ray spectroscopy.
      To evaluate cells-materials interaction, human osteosarcoma cell line (Saos-2)
      has been seeded on specimens and cell vitality evaluated by WST-8 assay.

PMID- 23533195
TI  - Endogenous distal airway progenitor cells, lung mechanics, and disproportionate
      lobar growth following long-term postpneumonectomy in mice.
AB  - Using a model of postpneumonectomy (PNY) compensatory lung growth in mice, we
      previously observed an increase in numbers of a putative endogenous distal airway
      progenitor cell population (CCSP(pos) /pro-SPC(pos) cells located at
      bronchoalveolar duct junctions [BADJs]), at 3, 7, and 14 days after
      pneumonectomy, returning to baseline at 28 days post-PNY. As the origin of these
      cells is poorly understood, we evaluated whether bone marrow cells contributed to
      the pool of these or other cells during prolonged post-PNY lung regrowth. Naive
      and sex-mismatched chimeric mice underwent left PNY and were evaluated at 1, 2,
      and 3 months for numbers of BADJ CCSP(pos) /pro-SPC(pos) cells and presence of
      donor-derived marrow cells engrafted as airway or alveolar epithelium.
      Nonchimeric mice were also examined at 12 months after PNY for numbers of BADJ
      CCSP(pos) /pro-SPC(pos) cells. Notably, the right accessory lobe (RAL) continued
      to grow disproportionately over 12 months, a novel finding not previously
      described. Assessment of lung mechanics demonstrated an increase in lung
      stiffness following PNY, which significantly diminished over 1 year, but remained
      elevated relative to 1-year-old naive controls. However, the number of CCSP(pos)
      /pro-SPC(pos) BADJ cells >=1-month following PNY was equivalent to that found in
      naive controls even after 12 months of continued RAL growth. Notably, no donor
      bone marrow-derived cells engrafted as airway or alveolar epithelial cells,
      including those at the BADJ, up to 3 months after PNY. These studies suggest that
      lung epithelial cells, including CCSP(pos) /pro-SPC(pos) cells, are not
      replenished from marrow-derived cells during post-PNY lung growth in mice.

PMID- 23533197
TI  - Promotion of osteoblast differentiation in mesenchymal cells through Cbl-mediated
      control of STAT5 activity.
AB  - The identification of the molecular mechanisms controlling the degradation of
      regulatory proteins in mesenchymal stromal cells (MSC) may provide clues to
      promote MSC osteogenic differentiation and bone regeneration. Ubiquitin ligase
      dependent degradation of proteins is an important process governing cell fate. In
      this study, we investigated the role of the E3 ubiquitin ligase c-Cbl in MSC
      osteoblast differentiation and identified the mechanisms involved in this effect.
      Using distinct shRNA targeting c-Cbl, we showed that c-Cbl silencing promotes
      osteoblast differentiation in murine and human MSC, as demonstrated by increased
      alkaline phosphatase activity, expression of phenotypic osteoblast marker genes
      (RUNX2, ALP, type 1 collagen), and matrix mineralization in vitro.
      Coimmunoprecipitation analyses showed that c-Cbl interacts with the transcription
      factor STAT5, and that STAT5 forms a complex with RUNX2, a master transcription
      factor controlling osteoblastogenesis. Silencing c-Cbl decreased c-Cbl-mediated
      STAT5 ubiquitination, increased STAT5 protein level and phosphorylation, and
      enhanced STAT5 and RUNX2 transcriptional activity. The expression of insulin like
      growth factor-1 (IGF-1), a target gene of STAT5, was increased by c-Cbl silencing
      in MSC and in bone marrow stromal cells isolated from c-Cbl deficient mice,
      suggesting that IGF-1 contributes to osteoblast differentiation induced by c-Cbl
      silencing in MSC. Consistent with these findings, pharmacological inhibition of
      STAT5 activity, or neutralization of IGF-1 activity, abrogated the positive
      effect of c-Cbl knockdown on MSC osteogenic differentiation. Taken together, the
      data provide a novel functional mechanism by which the ubiquitin ligase c-Cbl
      regulates the osteoblastic differentiation program in mesenchymal cells by
      controlling Cbl-mediated STAT5 degradation and activity.

PMID- 23533198
TI  - Enhanced bioactivity and osteoconductivity of hydroxyapatite through chloride
      substitution.
AB  - The effect of chloride-substitution on bioactivity and osteoconductivity of
      hydroxyapatite (OHAp) was newly investigated. Chloride-substituted
      hydroxyapatites (ClAp) with low and high chloride concentrations were synthesized
      by reacting Ca(OH)2 and H3 PO4 with NH4 Cl of low and high concentrations, with
      subsequent sintering. As a control, pure OHAp was prepared under the same
      conditions but without addition of NH4 Cl. The ClAp showed markedly enhanced
      bioactivity in simulated body fluid (SBF) as the chloride substitution was
      increased. In contrast, OHAp did not show any bioactivity at all within the
      testing period. The solubility tests in deionized water also showed that the
      higher the chloride-substituting amount, the higher the dissolution amounts of
      the constituent elements of apatite, which directly affect bioactivity by
      increasing the degree of supersaturation of apatite in SBF. In addition, ClAp
      also showed noticeably higher osteoconductivity within the 4 weeks of
      implantation in calvarial defects of New Zealand white rabbits, compared with
      that of OHAp. The total system energy of the apatite calculated by the ab initio
      method showed that the higher the chloride-substituting amount, the higher the
      total system energy, which suggests that the ClAp was energetically less stable
      compared with OHAp. This result demonstrates the higher solubility of ClAp over
      that of OHAp in SBF and deionized water. The improved solubility of the OHAp
      enhances its bioactivity and consequent osteoconductivity. Taken together, it can
      be concluded that ClAp has encouraging potential for use as a bone grafting
      material due to its highly enhanced bioactivity and osteoconductivity compared
      with pure OHAp.

PMID- 23533199
TI  - Severe kinking of the aortic arch associated with thoracic aortic dissection.

PMID- 23533200
TI  - A very unusual cause of mechanical left ventricular outflow tract obstruction.

PMID- 23533201
TI  - Huge pannus formation on a mechanical bileaflet mitral valve prosthesis 23 years
      after a third operation on the mitral valve.

PMID- 23533203
TI  - The challenge of mental health.

PMID- 23533202
TI  - Osteoblastic cell response on biphasic fluorhydroxyapatite/strontium-substituted
      hydroxyapatite coatings.
AB  - Fluorhydroxyapatite/strontium-substituted hydroxyapatite (FHA/SrHA) biphasic
      coatings with F and Sr elements incorporated simultaneously into one coating
      layer were prepared on titanium substrate via colloidal sol-gel method. The
      bioactivity of the as-prepared FHA/SrHA biphasic coatings was evaluated in vitro
      by immersion in simulated body fluid (SBF). All the biphasic coatings exhibited
      great ability to induce apatite precipitation on their surfaces. In vitro cell
      responses were evaluated using osteoblast-like MG63 cells in terms of cell
      proliferation and differentiation (alkaline phosphatase activity and osteocalcin
      level). The biphasic coatings show significantly positive effects on the
      viability and functional activity of osteoblastic cells with clear evidence that
      an optimum SrHA amount dose exists, indicating that the coexistence of FHA and
      SrHA had a synergistic stimulatory effect. This finding suggests the potential
      use of this colloidal sol-gel derived FHA/SrHA biphasic coatings for hard tissue
      applications.

PMID- 23533204
TI  - Food habits and preferences as a factor in the choice of meals by students in the
      University of Cape Coast.
AB  - The purpose of this study was to investigate food habits and preferences against
      menu planning for heterogeneous groups in institutions and to determine to what
      extent these results on food habits and preferences can be applied to practical
      recommendations in menu planning for heterogeneous groups. This study used data
      from a sample of students to determine whether food habits and preferences
      influence students' own menu planning and that of other eating outlets. A sample
      of 60 students within the University of Cape Coast campus was considered for this
      study. Findings from the study revealed that a greater number of students have
      altered their food habits over the years. This was attributed greatly to health
      factors, change of environment and education. The recommendations made in this
      study include encouraging cooking competitions among young people to expose them
      to traditional meals/dishes, which show culinary prowess, and also holding food
      fairs and encouraging teaching cooking methods for traditional dishes to
      children.

PMID- 23533205
TI  - Dietary fat intake, body composition and blood lipids of university men and
      women.
AB  - BACKGROUND: Cardiovascular disease rates are high in the U.K., particular in men,
      and are related to dietary fat intake. We conducted a pilot study to investigate
      relationships between saturated and unsaturated dietary fat intakes, body
      composition and blood lipid parameters in Caucasian men and women at university.
      METHODS: Volunteers (52 men and 52 women; age range 20-50 years) were recruited
      from staff and students of London Metropolitan University. Dietary intake, body
      composition, blood pressure and fasting blood glucose and lipids were assessed.
      Gender differences between the measured variables and their relationships were
      assessed by Mann-Whitney U-test, and by multi-linear (stepwise) regression,
      respectively. RESULTS: Men consumed more saturated fat (29.5 vs. 20.5 g/day, p <
      0.001), and had elevated levels of glucose (5.34 + 0.74 vs. 4.85 + 0.49 mmol/l, p
      < 0.001), low-density lipoprotein (LDL) cholesterol (2.99 + 1.5 vs. 2.62+ 0.74
      mmol/l, p < 0.05), systolic blood pressure (126.4 + 11.0 vs. 112.6 + 17.2 mm/Hg,
      p < 0.001), and lower high-density lipoprotein (HDL) cholesterol (1.41 +/- 0.34
      vs. 1.83 +/- 0.43, p < 0.001). Saturated fat was positively associated with total
      body fat ( p < 0.05), trunk fat ( p < 0.001), HDL cholesterol ( p < 0.05) and
      systolic blood pressure ( p < 0.001) in women, while in men docosahexaenoic acid
      and total cholesterol ( p < 0.05), total omega-3 fatty acids and LDL cholesterol
      ( p < 0.001), total omega-3 fatty acids and triglycerides ( p < 0.01) were
      positively related. Similar n-3 fatty acid intakes were reported in nutritionally
      aware students and other university subjects. CONCLUSIONS: The data of this study
      indicate gender-related differences in response to dietary fat, and widespread
      low compliance with n-3 fatty acid recommendations. Although the men are highly
      health conscious and physically active, their blood lipid levels are indicative
      of a risk of cardiovascular disease. In addition to enhanced nutritional
      education to increase seafood intakes in this age group of men and women,
      customised dietary and lifestyle advice may be required in the men.

PMID- 23533206
TI  - Phytochemical and nutrient/antinutrient interactions in cherry tomato
      (Lycopersicon esculentum) fruits.
AB  - The fruit of the cherry tomato (Lycopersicon esculentum (Solanaceae)) was
      analysed for mineral and antinutrient composition. Phosphorus (33.04 +/- 0.21
      mg/100g) was the most abundant mineral in the fruit, followed by calcium (32.04
      +/- 0.06 mg/100 g), and potassium (11.9 +/- 0.1 mg/100 g) and manganese (9.55 +/-
      0.28 mg/100 g) were also present in appreciable quantities. Antinutrients,
      including phytate, glycoside, saponin and tannin, were screened and quantified.
      Phytate (112.82 +/- 0.1 mg/100 g), glycoside (2.33 +/- 0.00 mg/100 g), saponin
      (1.31 +/- 0.00 mg/100g) and tannin (0.21 +/- 0.00 mg/100 g) were present in the
      fruit but phlobatanin and glycosides with steroidal rings were not found. The
      calculated calcium:phytate ratio of the fruits was below the critical value and
      the calculated [calcium] [phytate]:[zinc] molar ratio was less than the critical
      value. The calcium:phosphorus ratio (0.97 mg/100 g) shows the fruit to be a good
      source of food nutrients, while the sodium:potassium value was less than 1. Ca/P
      ratio below 0.5 indicates deficiency of these minerals while Na/K ratio above 1
      is detrimental because of excessive sodium levels. The results of the study
      generally revealed the fruit to be rich in minerals but containing insufficient
      quantities of antinutrients to result in poor mineral bioavailability.

PMID- 23533208
TI  - Xrays aren't always right...

PMID- 23533209
TI  - Surface plasmon resonance: a useful technique for cell biologists to characterize
      biomolecular interactions.
AB  - Surface plasmon resonance (SPR) is a powerful technique for monitoring the
      affinity and selectivity of biomolecular interactions. SPR allows for analysis of
      association and dissociation rate constants and modeling of biomolecular
      interaction kinetics, as well as for equilibrium binding analysis and ligand
      specificity studies. SPR has received much use and improved precision in
      classifying protein-protein interactions, as well as in studying small-molecule
      ligand binding to receptors; however, lipid-protein interactions have been
      underserved in this regard. With the field of lipids perhaps the next frontier in
      cellular research, SPR is a highly advantageous technique for cell biologists, as
      newly identified proteins that associate with cellular membranes can be screened
      rapidly and robustly for lipid specificity and membrane affinity. This technical
      perspective discusses the conditions needed to achieve success with lipid-protein
      interactions and highlights the unique lipid-protein interaction mechanisms that
      have been elucidated using SPR. It is intended to provide the reader a framework
      for quantitative and confident conclusions from SPR analysis of lipid-protein
      interactions.

PMID- 23533210
TI  - Magazine or journal--what is the difference? The role of the monitoring editor.
AB  - Scientific communication, career advancement, and funding decisions are all
      dependent on research publications. The way manuscripts are handled by high
      visibility, professionally edited magazines differs from the way academic
      journals evaluate manuscripts, using active scientists as monitoring editors. In
      this essay, I discuss the benefits that come with the involvement of active
      scientists. I enumerate the decisions a monitoring editor has to make, and how he
      or she goes about making them. Finally, I indicate ways in which authors can help
      to make the process a smoother and more positive experience.

PMID- 23533211
TI  - Ethical and professional concerns in research utilisation: intentional rounding
      in the United Kingdom.
AB  - Intentional rounding, a process involving the performance of regular checks on
      all patients following a standardised protocol, is being introduced widely in the
      United Kingdom. The process has been promoted by the Prime Minister and
      publicised by the Chief Nursing Officer at the Department of Health as well as by
      influential think tanks and individual National Health Service organisations. An
      evidence base is offered in justification. This article subjects the evidence
      base to critical scrutiny concluding that it consists of poor quality studies and
      serial misreporting of findings and a failure to consider wider concerns,
      including transference of evidence to differing health-care systems, and the
      conflation of perception and quality of care. Political promotion and wide
      implementation of intentional rounding despite the flimsy and questionable
      evidence base raise questions about the use of evidence in ethical nursing
      practice and the status of nursing as an autonomous profession. 

PMID- 23533212
TI  - Recurring and generalized visceroptosis in Ehlers-Danlos syndrome hypermobility
      type.
AB  - Visceroptosis is described in several heritable connective tissue disorders,
      including the hypermobility type of Ehlers-Danlos syndrome (hEDS), a.k.a. joint
      hypermobility syndrome (JHS). Clinical features of hEDS comprise joint
      hypermobility, mild skin hyperextensibility, joint instability complications,
      chronic joint/limb pain, and positive family history. Uterine and rectal prolapse
      has been reported in nulliparous women. We report on a family with two patients
      with hEDS. The proposita, a 38-year-old woman, present bilateral kidney prolapse
      requiring three nephropexies, gastric ptosis treated with gastropexy and Billroth
      I gastrectomy, and liver prolapse treated with a non-codified hepatopexy
      procedure. Radiological evaluation also showed ovarian and heart prolapse. To our
      knowledge this is the first case of multiple visceral ptoses in hEDS. Visceral
      prolapse may lead to severe morbidity, affecting quality of life and a high rate
      of relapses after surgical procedures. Further investigations are needed to
      understand the molecular basis of the disease and retrospective studies on
      surgical outcomes, presentation of case series can be effective in order to offer
      a better treatment and prevention for hEDS patients.

PMID- 23533213
TI  - Can a psychosocial intervention programme teaching coping strategies improve the
      quality of life of Iranian women? A non-randomised quasi-experimental study.
AB  - OBJECTIVES: To assess whether a psychosocial intervention teaching coping
      strategies to women can improve quality of life (QOL) in groups of Iranian women
      exposed to social pressures. DESIGN: Quasi-experimental non-randomised group
      design involving two categories of Iranian women, each category represented by
      non-equivalent intervention and comparison groups. SETTING: A large urban area in
      Iran. PARTICIPANTS: 44 women; 25 single mothers and 19 newly married women.
      INTERVENTIONS: Seventh-month psychosocial intervention aimed at providing coping
      strategies. PRIMARY OUTCOME MEASURES: Effect sizes in four specific health
      related domains and two overall perceptions of QOL and health measured by the
      WHOQOL-BREF instrument. RESULTS: Large effect sizes were observed among the women
      exposed to the intervention in the WHOQOL-BREF subdomains measuring physical
      health (r=0.68; p<0.001), psychological health (r=0.72; p<0.001), social
      relationships (r=0.52; p<0.01), environmental health (r=0.55; p<0.01) and in the
      overall perception of QOL (r=0.72; p<0.001); the effect size regarding overall
      perception of health was between small and medium (r=0.20; not significant).
      Small and not statistically significant effect sizes were observed in the women
      provided with traditional social welfare services. CONCLUSIONS: Teaching coping
      strategies can improve the QOL of women in societies where gender discrimination
      is prevalent. The findings require reproduction in studies with a more rigorous
      design before the intervention model can be recommended for widespread
      distribution.

PMID- 23533214
TI  - Incidence and risk factors for mortality of vertebral osteomyelitis: a
      retrospective analysis using the Japanese diagnosis procedure combination
      database.
AB  - OBJECTIVE: To examine the incidence of vertebral osteomyelitis (VO) and the
      clinical features of VO focusing on risk factors for death using a Japanese
      nationwide administrative database. DESIGN: Retrospective observational study.
      SETTING: Hospitals adopting the Diagnosis Procedure Combination system during
      2007-2010. PARTICIPANTS: We identified 7118 patients who were diagnosed with VO
      (International Classification of Diseases, 10th Revision codes: A18.0, M46.4,
      M46.5, M46.8, M46.9, M48.9 and M49.3, checked with the detailed diagnoses in each
      case and all other codes indicating the presence of a specific infection) and
      hospitalised between July and December, 2007-2010, using the Japanese Diagnosis
      Procedure Combination database. MAIN OUTCOME MEASURES: The annual incidence of VO
      was estimated. Logistic regression analysis was performed to analyse factors
      affecting in-hospital mortality in the VO patients. Dependent variables included
      patient characteristics (age, sex and comorbidities), procedures (haemodialysis
      and surgery) and hospital factors (type of hospital and hospital volume).
      RESULTS: Overall, 58.9% of eligible patients were men and the average age was
      69.2 years. The estimated incidence of VO increased from 5.3/100 000 population
      per year in 2007 to 7.4/100 000 population per year in 2010. In-hospital
      mortality was 6%. There was a linear trend between higher rates of in-hospital
      mortality and greater age. A higher rate of in-hospital mortality was
      significantly associated with haemodialysis use (ORs, 10.56 (95% CI 8.12 to
      13.74)), diabetes (2.37 (1.89 to 2.98)), liver cirrhosis (2.63 (1.49 to 4.63)),
      malignancy (2.68, (2.10 to 3.42)) and infective endocarditis (3.19 (1.80 to
      5.65)). CONCLUSIONS: Our study demonstrates an increasing incidence of VO, and
      defines risk factors for death with a nationwide database. Several comorbidities
      were significantly associated with higher rates of in-hospital death in VO
      patients.

PMID- 23533215
TI  - Myocardial function in premature infants: a longitudinal observational study.
AB  - OBJECTIVES: Gestational and chronological age may have an impact on myocardial
      function. We studied the longitudinal changes of the atrioventricular tissue
      Doppler velocities in premature infants through the neonatal transitional period
      and at expected term and explored the reproducibility of the measurements.
      DESIGN: Prospective, observational and longitudinal cohort study. SETTING: Two
      centre study, from a secondary and a tertiary neonatal intensive care unit.
      PARTICIPANTS: 55 infants (29 males) with gestational age 31-35 weeks and birth
      weight 1127-2836 grams. PRIMARY AND SECONDARY OUTCOME MEASURES: Pulsed-wave
      atrioventricular left, septum and right ventricular annulus tissue Doppler
      systolic (S'), early diastolic (E') and late diastolic (A') velocities measured
      by repeated echocardiographic examinations days 1, 2 and 3 and at expected term.
      RESULTS: All velocities increased significantly from the neonatal period to
      expected term (p<0.001). We found a significant correlation between gestational
      age and right-sided S', E' and A' on day 1 (Pearson correlation 0.32-0.46,
      p<0.05), for S' in all three walls and septal E' and A' on day 2 (Pearson
      correlation 0.27-0.49, p<0.05). There was a moderate linear correlation between
      left ventricle end-diastolic length and septal and right S' at term and for
      septal E' and A' at day 1 (Pearson correlation 0.30-0.56, p<0.05). We found no
      correlation between heart rate and tissue Doppler velocities when controlling for
      the effect of fusion. Continuous positive airway pressure showed moderate effect
      where as persistence of the ductus arteriosus showed no effect on the tissue
      Doppler velocities. The E'/A' relationship was consistently reversed throughout
      the study with frequently fused diastolic tissue velocity signals. CONCLUSIONS:
      Pulsed-wave atrioventricular annulus tissue Doppler velocities were related to
      gestational age, postnatal age and ventricular size. Right ventricle velocities
      showed more pronounced increase with postnatal maturation than left ventricle
      velocities. The degree of E'/A' fusion influenced the diastolic tissue Doppler
      velocities and should be reported if present.

PMID- 23533216
TI  - Descriptive study of possible link between cardioankle vascular index and
      homocysteine in vascular-related diseases.
AB  - OBJECTIVES: Cardioankle vascular index (CAVI) is a new index of arterial
      stiffness independent of immediate blood pressure. Homocysteine (Hcy) is an
      independent risk factor for vascular diseases. The aim of this study was to
      investigate the relationship between Hcy and CAVI in the vascular-related
      diseases. DESIGN: Descriptive research. PARTICIPANTS: 88 patients (M/F 46/42)
      with or without hypertension, coronary artery disease or arteriosclerosis
      obliterans were enrolled to our study. They were divided into two groups
      according to the level of Hcy. METHODS: CAVI, carotid-femoral pulse wave velocity
      (CF-PWV) and carotid-radial pulse wave velocity (CR-PWV) were measured by VS-1000
      and Complior apparatus. RESULTS: There was significant correlation between Hcy
      and CF-PWV, CR-PWV, CAVI in the entire group (r=0.33, p=0.002; r=0.51, p<0.001;
      r=0.42, p<0.001, respectively). And there was significant correlation between Hcy
      and CF-PWV, CR-PWV, CAVI in the vascular-related disease group (r=0.23, p=0.048;
      r=0.51, p<0.001; r=0.392, p=0.001, respectively). The level of Hcy was
      significantly higher in patients with one or more vascular diseases than in
      patients without vascular diseases. The levels of CF-PWV, CR-PWV and CAVI were
      significantly higher in Hcy >=15 MUmol/l group than in Hcy <5 MUmol/l group
      (13.7+/-3.0 vs 10.8+/-2.5, p < 0.001; 10.6+/-2.1 vs 9.2+/-1.6, p=0.001; 9.30+/
      2.1 vs 7.79+/-2.1, p=0.001, respectively). Multiple linear regression showed that
      Hcy, body mass index (BMI) and age were independent associating factors of CAVI
      in the entire study group (beta=0.421, p=0.001; beta=-0.309, p=0.006; beta=0.297,
      p=0.012, respectively). And Hcy, BMI and age were independent influencing factors
      of CAVI in the vascular-related disease group (beta=0.434, p=0.001; beta=-0.331,
      p=0.009; beta=0.288, p=0.022, respectively). CONCLUSIONS: CAVI was positively
      correlated with Hcy in the vascular-related diseases.

PMID- 23533217
TI  - Would primary healthcare professionals prescribe a polypill to manage
      cardiovascular risk? A qualitative interview study.
AB  - OBJECTIVES: A 'polypill' containing both blood pressure-lowering and cholesterol
      lowering drugs could prevent up to 80% of cardiovascular disease events. Since
      little is known about the attitudes of primary healthcare professionals to use of
      such a pill for cardiovascular disease prevention, this study aimed to
      investigate opinions. DESIGN: Semistructured interviews were conducted with
      participants. A qualitative description approach was used to analyse and report
      the results. SETTING: Participants were recruited from nine primary care
      practices in Birmingham. PARTICIPANTS: Sixteen healthcare professionals (11
      primary care physicians and 5 practice nurses) were selected through purposive
      sampling to maximise variation of characteristics. OUTCOME MEASURES: Outcome
      measures for this study were: the attitude of healthcare professionals towards
      the use of a polypill for primary and secondary cardiovascular disease
      prevention; their views on monitoring the drug; and the factors influencing their
      willingness to prescribe the medication. RESULTS: Healthcare professionals
      expressed considerable concern over using a polypill for primary prevention for
      all people over a specific age, although there was greater acceptance of its use
      for secondary prevention. Regularly monitoring patients taking the polypill was
      deemed essential. Evidence of effectiveness, patient risk level and potential
      medicalisation were key determinants in willingness to prescribe such a pill.
      CONCLUSIONS: Primary healthcare professionals have significant concerns about the
      use of a polypill, particularly in the prevention of cardiovascular disease in
      people who are not regarded as being at 'high risk'. If a population-based
      polypill strategy is to be successfully implemented, healthcare professionals
      will need to be convinced of the potential benefits of a drug-based population
      approach to prevention.

PMID- 23533218
TI  - Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by
      epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies.
AB  - OBJECTIVES: Coenzyme Q10 (CoQ10) deficiency syndrome is a rare condition that
      causes mitochondrial dysfunction and includes a variety of clinical presentations
      as encephalomyopathy, ataxia and renal failure. First, we sought to set up what
      all have in common, and then investigate why CoQ10 supplementation reverses the
      bioenergetics alterations in cultured cells but not all the cellular phenotypes.
      DESIGN MODELLING STUDY: This work models the transcriptome of human CoQ10
      deficiency syndrome in primary fibroblast from patients and study the genetic
      response to CoQ10 treatment in these cells. SETTING: Four hospitals and medical
      centres from Spain, Italy and the USA, and two research laboratories from Spain
      and the USA. PARTICIPANTS: Primary cells were collected from patients in the
      above centres. MEASUREMENTS: We characterised by microarray analysis the
      expression profile of fibroblasts from seven CoQ10-deficient patients (three had
      primary deficiency and four had a secondary form) and aged-matched controls,
      before and after CoQ10 supplementation. Results were validated by Q-RT-PCR. The
      profile of DNA (CpG) methylation was evaluated for a subset of gene with
      displayed altered expression. RESULTS: CoQ10-deficient fibroblasts (independently
      from the aetiology) showed a common transcriptomic profile that promotes cell
      survival by activating cell cycle and growth, cell stress responses and
      inhibiting cell death and immune responses. Energy production was supported
      mainly by glycolysis while CoQ10 supplementation restored oxidative
      phosphorylation. Expression of genes involved in cell death pathways was
      partially restored by treatment, while genes involved in differentiation, cell
      cycle and growth were not affected. Stably demethylated genes were unaffected by
      treatment whereas we observed restored gene expression in either non-methylated
      genes or those with an unchanged methylation pattern. CONCLUSIONS: CoQ10
      deficiency induces a specific transcriptomic profile that promotes cell survival,
      which is only partially rescued by CoQ10 supplementation.

PMID- 23533219
TI  - Increased activin bioavailability enhances hepatic insulin sensitivity while
      inducing hepatic steatosis in male mice.
AB  - The development of insulin resistance is tightly linked to fatty liver disease
      and is considered a major health concern worldwide, although their mechanistic
      relationship remains controversial. Activin has emerging roles in nutrient
      homeostasis, but its metabolic effects on hepatocytes remain unknown. In this
      study, we investigated the effects of increased endogenous activin bioactivity on
      hepatic nutrient homeostasis by creating mice with inactivating mutations that
      deplete the circulating activin antagonists follistatin-like-3 (FSTL3) or the
      follistatin 315 isoform (FST315; FST288-only mice). We investigated liver
      histology and lipid content, hepatic insulin sensitivity, and metabolic gene
      expression including the HepG2 cell and primary hepatocyte response to activin
      treatment. Both FSTL3-knockout and FST288-only mice had extensive hepatic
      steatosis and elevated hepatic triglyceride content. Unexpectedly, insulin
      signaling, as assessed by phospho-Akt (a.k.a. protein kinase B), was enhanced in
      both mouse models. Pretreatment of HepG2 cells with activin A increased their
      response to subsequent insulin challenge. Gene expression analysis suggests that
      increased lipid uptake, enhanced de novo lipid synthesis, decreased lipolysis,
      and/or enhanced glucose uptake contribute to increased hepatic triglyceride
      content in these models. However, activin treatment recapitulated only some of
      these gene changes, suggesting that increased activin bioactivity may be only
      partially responsible for this phenotype. Nevertheless, our results indicate that
      activin enhances hepatocyte insulin response, which ultimately leads to hepatic
      steatosis despite the increased insulin sensitivity. Thus, regulation of activin
      bioactivity is critical for maintaining normal liver lipid homeostasis and
      response to insulin, whereas activin agonists may be useful for increasing liver
      insulin sensitivity.

PMID- 23533221
TI  - Oral tongue squamous cell carcinoma in never-smokers: analysis of
      clinicopathologic characteristics and survival.
AB  - OBJECTIVES: (1) To compare clinical characteristics, survival, and recurrence
      between never-smokers and ever-smokers with oral tongue squamous cell carcinoma
      (OTSCC). (2) To assess the relationship between clinicopathologic characteristics
      and survival/recurrence in OTSCC. STUDY DESIGN: Historical cohort study. SETTING:
      Academic university medical center. SUBJECTS AND METHODS: This is a study of 120
      patients with OTSCC who were treated from January 1999 to February 2010.
      Clinicopathologic factors were compared between never-smokers and ever-smokers
      using t tests and chi(2) tests. Cox regression analyses examined their
      association with survival and recurrence. RESULTS: Of 120 subjects, 66 (55%) were
      prior or current smokers. There were no significant differences in
      clinicopathologic factors between ever-smokers and never-smokers. After
      adjustment for clinicopathologic factors, multivariate Cox regression analysis
      demonstrated decreased overall survival for never-smokers, but this difference
      was not significant (hazard ratio [HR], 2.84; P = .056). Increased depth of tumor
      invasion (HR per millimter invasion, 1.09; P = .005), nodal metastasis (HR, 7.1;
      P = .025), and stage III or IV disease (HR, 9.45 and 7.31; P = .026 and .029,
      respectively) were associated with decreased overall survival. Perineural
      invasion (HR, 8.56; P = .005) and lymphovascular invasion (HR, 6.01; P = .011)
      were associated with disease recurrence. CONCLUSION: Overall survival may be
      decreased in never-smokers with OTSCC. Greater depth of tumor invasion and more
      advanced stage disease are associated with decreased survival. Perineural
      invasion and lymphovascular invasion are associated with disease recurrence.

PMID- 23533220
TI  - Enhanced striatal beta1-adrenergic receptor expression following hormone loss in
      adulthood is programmed by both early sexual differentiation and puberty: a study
      of humans and rats.
AB  - After reproductive senescence or gonadectomy, changes occur in neural gene
      expression, ultimately altering brain function. The endocrine mechanisms
      underlying these changes in gene expression beyond immediate hormone loss are
      poorly understood. To investigate this, we measured changes in gene expression
      the dorsal striatum, where 17beta-estradiol modulates catecholamine signaling. In
      human caudate, quantitative PCR determined a significant elevation in beta1
      adrenergic receptor (beta1AR) expression in menopausal females when compared with
      similarly aged males. No differences were detected in beta2-adrenergic and D1-
      and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized
      female rats exhibited a similar increase in beta1AR expression when compared with
      gonadectomized males. No sex difference in beta1AR expression was detected
      between intact adults, prepubertal juveniles, or adults gonadectomized before
      puberty, indicating the necessity of pubertal development and adult ovariectomy.
      Additionally, increased beta1AR expression in adult ovariectomized females was
      not observed if animals were masculinized/defeminized with testosterone
      injections as neonates. To generate a model system for assessing functional
      impact, increased beta1AR expression was induced in female-derived cultured
      striatal neurons via exposure to and then removal of hormone-containing serum.
      Increased beta1AR action on cAMP formation, cAMP response element-binding protein
      phosphorylation and gene expression was observed. This up-regulation of beta1AR
      action was eliminated with 17beta-estradiol addition to the media, directly
      implicating this hormone as a regulator of beta1AR expression. Beyond having
      implications for the known sex differences in striatal function and pathologies,
      these data collectively demonstrate that critical periods early in life and at
      puberty program adult gene responsiveness to hormone loss after gonadectomy and
      potentially reproductive senescence.

PMID- 23533222
TI  - No gene-specific optimization of mutation rate in Escherichia coli.
AB  - Mutation rate is one of the most fundamental parameters in genetics and
      evolutionary biology because mutation rate has major impacts on the incidence of
      disease, the amount of genetic variation, and the rate and trajectory of
      evolution. Based on estimates of synonymous nucleotide diversity in Escherichia
      coli, a recent study claimed that the per-nucleotide mutation rate in a gene
      decreases with the rise of its expression level or the intensity of purifying
      selection and that this trend reflects adaptive risk management. Here, we
      demonstrate that this argument is theoretically untenable, especially in the lack
      of mechanisms that simultaneously tune the mutabilities of multiple genes with
      similar fractions of deleterious mutations. Analyzing published genome sequences
      of E. coli mutation accumulation lines, we show that mutation rates are actually
      higher in more highly expressed genes, similar to previous genome-wide
      observations in Salmonella typhimurium, Saccharomyces cerevisiae, and the human
      germline. These general patterns likely arise from transcription-associated
      mutagenesis that exceeds transcription-coupled repair.

PMID- 23533223
TI  - Steps forward, backward, and sideways: intravenous lipid emulsions for critically
      ill neonates.

PMID- 23533224
TI  - Distinct relationships of intramuscular and subcutaneous fat with cortical bone:
      findings from a cross-sectional study of young adult males and females.
AB  - CONTEXT: Intracellular fat within muscle and visceral tissue has been suggested
      to adversely influence bone development. OBJECTIVE: The aim of the study was to
      evaluate associations between im fat, as reflected by muscle density as measured
      by peripheral quantitative computed tomography, and cortical bone parameters in
      young adults. DESIGN/SETTING/PARTICIPANTS: We conducted a cross-sectional
      analysis of 1703 males and 2243 females aged 17.8 years from the Avon
      Longitudinal Study of Parents and Children. OUTCOME MEASURES: We measured
      cortical bone parameters from midtibial peripheral quantitative computed
      tomography scans. RESULTS: Muscle density (inversely related to im fat) was
      inversely associated with periosteal circumference (PC) (beta = -0.07 [95%
      confidence interval (CI), -0.1, -0.04]), cortical bone mineral density (BMDC)
      (beta = -0.21 [95% CI, -0.26, -0.17]), and cortical thickness (CT) (beta = -0.37
      [95% CI, -0.42, -0.33]) (males and females combined, adjusted for age, height,
      gender, and muscle cross-sectional area). In contrast, sc fat area was positively
      associated with PC (beta = 0.10 [95% CI, 0.07, 0.12]), but no association was
      seen with BMDC or CT. To examine the role of candidate intermediary metabolic
      pathways, analyses were repeated after adjustment for insulin, C-reactive
      protein, and beta-C-telopeptides of type I collagen. Whereas similar associations
      were observed after adjustment for insulin and C-reactive protein, the
      association between muscle density and BMDC was partially attenuated by
      adjustment for beta-C-telopeptides of type I collagen (beta = -0.14 [95% CI, 
      0.20, -0.08]). CONCLUSION: Although im and sc fat were both positively associated
      with cortical bone mass, the nature of these relationships differed in that im
      fat was predominantly associated with CT and BMDC, whereas sc fat was mainly
      associated with PC. These relationships were largely independent of candidate
      metabolic pathways, such as altered bone resorption, insulin resistance, or
      inflammation.

PMID- 23533225
TI  - Clinical relevance of combined FSH and AMH observations in infertile women.
AB  - CONTEXT: FSH and anti-Mullerian hormone (AMH) are, individually, widely used to
      assess functional ovarian reserve (FOR) but demonstrate discrepancies in
      efficacy. How predictive they are combined is unknown. OBJECTIVE: The purpose of
      this study was to assess predictive values of different FSH and AMH combinations
      on in vitro fertilization (IVF). DESIGN AND SETTING: FSH and AMH levels in
      patients were categorized as low, normal, and high, based on age-specific 95%
      confidence intervals. This allowed for establishment of nine combinations of low,
      normal, or high FSH/AMH patient categories. With use of various statistical
      methods, patients in individual categories were then compared in outcomes.
      PATIENTS: We investigated 544 consecutive infertility patients in their first IVF
      cycles. INTERVENTIONS: IVF cycles were managed. MAIN OUTCOME MEASURES: Oocyte
      yields and implantation and pregnancy rates, adjusted for age and fragile X
      mental retardation 1 (FMR1) genotypes/subgenotypes, were measured. RESULTS: The
      most notable repeated finding was a strong statistical association of the FSH/AMH
      high/high category (characterized by abnormally high FSH and AMH levels) with
      favorable IVF outcomes compared with outcomes for other FSH/AMH variations (4.34
      times odds of high oocyte yields and 1.93 times odds of clinical pregnancy).
      Addition of age to the model only minimally further improved the odds of
      pregnancy to 2.03 times. The positive association with high oocyte yields,
      however, turned negative (0.75 times lower yields) with addition of FMR1 to the
      model for women with FSH/AMH high/high and the het-norm/low FMR1 subgenotype
      compared with women with the norm FMR1 genotype and other FSH/AMH categories.
      CONCLUSIONS: In the absence of het-norm/low FMR1, abnormally high FSH and AMH, a
      seemingly contradictory combination, reflects highly beneficial outcomes in IVF
      compared with the other FSH/AMH categories, suggesting greater importance of FSH
      in early follicle maturation than currently recognized. The study also confirms
      adverse outcome effects of het-norm/low FMR1 and, therefore, the gene's
      importance for reproductive success.

PMID- 23533226
TI  - Cortical and trabecular bone density in X-linked hypophosphatemic rickets.
AB  - CONTEXT: X-linked hypophosphatemic rickets is caused by mutations in PHEX. Even
      though the disease is characterized by disordered skeletal mineralization,
      detailed bone densitometric studies are lacking. OBJECTIVE: The aim of the study
      was to assess volumetric bone mineral density (vBMD) in X-linked hypophosphatemic
      rickets using forearm peripheral quantitative computed tomography. SETTING: The
      study was conducted in the metabolic bone clinic of a pediatric orthopedic
      hospital. PATIENTS: Thirty-four patients (age, 6 to 60 years; 24 female) with
      PHEX mutations were studied, of whom 7 children (age, 6 to 11 years) were
      actively being treated with calcitriol and phosphate supplementation. Twenty-one
      patients (age, 16 to 40 years) had received the same therapy before but had
      discontinued the treatment; 6 patients (age, 12 to 60 years) had never received
      this treatment. MAIN OUTCOME MEASURES: Trabecular and cortical vBMD of the
      radius. RESULTS: Trabecular vBMD was elevated (mean age-specific and sex-specific
      z-score: +1.0) when all patients were analyzed together, due to very high results
      in currently treated patients (mean z-score: +2.4) and slightly above-average
      mean values in the other patients. Cortical vBMD was low when the entire cohort
      was analyzed together (mean z-score: -3.3), but was higher in currently treated
      patients (mean z-score: -1.3) than in patients who had discontinued therapy (mean
      z-score: -3.8) or who had never been treated (mean z-score: -4.1). CONCLUSIONS:
      Patients with PHEX mutations have elevated trabecular vBMD at the distal radius
      while receiving calcitriol and phosphate supplementation, but low cortical vBMD
      at the radius diaphysis. Low cortical vBMD presumably reflects the underlying
      mineralization defect that is not entirely corrected by current treatment
      approaches.

PMID- 23533227
TI  - Effects of testosterone and progressive resistance exercise in healthy, highly
      functioning older men with low-normal testosterone levels.
AB  - CONTEXT: Aging in men is associated with reduced testosterone (T) levels and
      physiological changes leading to frailty, but the benefits of T supplementation
      are inconclusive. OBJECTIVE: We studied the effects of T supplementation with and
      without progressive resistance training (PRT) on functional performance,
      strength, and body composition. DESIGN, SETTING, AND PARTICIPANTS: We recruited
      167 generally healthy community-dwelling older men (66 +/- 5 years) with low
      normal baseline total T levels (200-350 ng/dL). INTERVENTION: Subjects were
      randomized to placebo or transdermal T gel [2 doses targeting either a lower (400
      550 ng/dL) or higher (600-1000 ng/dL) T range] and to either PRT or no exercise
      for 12 months. MAIN OUTCOME MEASURE: The primary outcome was functional
      performance, whereas secondary outcomes were strength and body composition.
      RESULTS: A total of 143 men completed the study. At 12 months, total T was 528 +/
      287 ng/dL in subjects receiving any T and 287 +/- 65 ng/dL in the placebo group.
      In the PRT group, function and strength were not different between T- and placebo
      treated subjects, despite greater improvements in fat mass (P = .04) and fat-free
      mass (P = .01) with T. In the non-PRT group, T did not improve function but
      improved fat mass (P = .005), fat-free mass (P = .03), and upper body strength (P
      = .03) compared with placebo. There were fewer cardiovascular events in the T
      treated groups compared with placebo. CONCLUSIONS: T supplementation was well
      tolerated and improved body composition but had no effect on functional
      performance. T supplementation improved upper body strength only in nonexercisers
      compared with placebo.

PMID- 23533229
TI  - Reproductive and lifestyle determinants of anti-Mullerian hormone in a large
      population-based study.
AB  - CONTEXT: Anti-mullerian hormone (AMH) is an ovarian reserve marker that is
      increasingly applied in clinical practice as a prognostic and diagnostic tool.
      Despite increased use of AMH in clinical practice, large-scale studies addressing
      the influence of possible determinants on AMH levels are scarce. OBJECTIVE: We
      aimed to address the role of reproductive and lifestyle determinants of AMH in a
      large population-based cohort of women. DESIGN: In this cross-sectional study,
      age-specific AMH percentiles were calculated using general linear modeling with
      CG-LMS (Cole and Green, Lambda, Mu, and Sigma model, an established method to
      calculate growth curves for children). SETTING: Women from the general community
      participating in the Doetinchem Cohort study were assessed. PARTICIPANTS: Two
      thousand three hundred twenty premenopausal women were included. MAIN OUTCOME
      MEASURE: The effect of female reproductive and lifestyle factors on shifts in age
      specific AMH percentiles was studied. RESULTS: In comparison to women with a
      regular menstrual cycle, current oral contraceptive (OC) users, women with
      menstrual cycle irregularity, and pregnant women had significantly lower age
      specific AMH percentiles (for OC use, 11 percentiles lower; for cycle
      irregularity, 11 percentiles lower; and for pregnancy, 17 percentiles lower [P
      value for all <.0001]). Age at menarche and age at first childbirth were not
      associated with the age-specific AMH percentile. Higher parity was associated
      with 2 percentiles higher age-specific AMH (P = .02). Of the lifestyle factors
      investigated, current smoking was associated with 4 percentiles lower age
      specific AMH percentiles (P = .02), irrespective of the smoking dose. Body mass
      index, waist circumference, alcohol consumption, physical exercise, and
      socioeconomic status were not significantly associated with age-specific AMH
      percentiles. CONCLUSIONS: This study demonstrates that several reproductive and
      lifestyle factors are associated with age-specific AMH levels. The lower AMH
      levels associated with OC use and smoking seem reversible, as effects were
      confined to current use of OC or cigarettes. It is important to give careful
      consideration to the effect of such determinants when interpreting AMH in a
      clinical setting and basing patient management on AMH.

PMID- 23533228
TI  - Prioritizing genetic testing in patients with Kallmann syndrome using clinical
      phenotypes.
AB  - CONTEXT: The complexity of genetic testing in Kallmann syndrome (KS) is growing
      and costly. Thus, it is important to leverage the clinical evaluations of KS
      patients to prioritize genetic screening. OBJECTIVE: The objective of the study
      was to determine which reproductive and nonreproductive phenotypes of KS subjects
      have implications for specific gene mutations. SUBJECTS: Two hundred nineteen KS
      patients were studied: 151 with identified rare sequence variants (RSVs) in 8
      genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2)
      and 68 KS subjects who remain RSV negative for all 8 genes. MAIN OUTCOME
      MEASURES: Reproductive and nonreproductive phenotypes within each genetic group
      were measured. RESULTS: Male KS subjects with KAL1 RSVs displayed the most severe
      reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 +/-
      0.1 mL vs 3.7 +/- 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes,
      synkinesia was enriched but not unique to patients with KAL1 RSVs compared with
      KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and
      digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1
      signaling pathway compared with all other gene groups combined (39% vs 4% and 23%
      vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs
      (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate
      did not emerge as statistically significant phenotypic predictors. CONCLUSIONS:
      Certain clinical features in men and women are highly associated with genetic
      causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony
      abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for
      prioritizing genetic screening.

PMID- 23533231
TI  - Pituitary stalk lesions: the Mayo Clinic experience.
AB  - CONTEXT: Pituitary stalk lesions have various etiologies, often not clinically
      apparent. Pathological samples from these lesions are rarely obtained, because of
      the critical location and function of the hypophyseal stalk. OBJECTIVES: The
      purpose of this study was to characterize the etiological spectrum of pituitary
      stalk lesions seen at Mayo Clinic Rochester over 20 years and to determine
      whether specific magnetic resonance imaging (MRI) characteristics could provide
      clinician guidance with regard to the etiology of infundibular lesions. DESIGN: A
      retrospective review of patients with pituitary stalk lesions seen at Mayo Clinic
      Rochester between 1987 and 2006 was conducted. Demographic, clinical
      presentation, imaging, laboratory, operative, and pathology data were reviewed
      and are reported using descriptive statistics. RESULTS: Of the 152 pituitary
      stalk lesions included, 49 (32%) were neoplastic, 30 (20%) were inflammatory, 13
      (9%) were congenital anomalies, and 60 (39%) were of unclear etiology. Diabetes
      insipidus was diagnosed in 43 (28%) of the 152 patients, and 49 (32%) patients
      had at least one anterior pituitary hormone deficit. Secondary hypogonadism was
      the most common endocrine deficiency. Eleven of 13 congenital lesions were round
      in appearance and 5 of 7 patients with neurosarcoidosis confirmed by pathology
      had a uniformly thickened pituitary stalk on MRI. There were no statistically
      significant correlations between hypopituitarism and the pattern of enhancement
      or size of the lesion. CONCLUSIONS: Findings on MRI remain key in guiding the
      diagnosis of pituitary stalk lesions, particularly when used in conjunction with
      other clinical clues. There are no good imaging predictors for hypopituitarism,
      making clinical evaluation of all patients with pituitary stalk lesions crucial.

PMID- 23533230
TI  - Response of the insulin-like growth factor (IGF) system to IGF-IR inhibition and
      androgen deprivation in a neoadjuvant prostate cancer trial: effects of obesity
      and androgen deprivation.
AB  - CONTEXT: Prostate cancer patients at increased risk for relapse after
      prostatectomy were treated in a neoadjuvant study with androgen deprivation
      therapy (ADT) in combination with cixutumumab, an inhibitory fully human
      monoclonal antibody against IGF receptor 1 (IGF-IR). OBJECTIVE: A clinical trial
      with prospective collection of serum and tissue was designed to test the
      potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in
      these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin
      components to IGF-IR blockade was also examined. DESIGN: Eligibility for the
      trial required the presence of high-risk prostate adenocarcinoma. Treatment
      consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before
      prostatectomy. Here we report on an analysis of serum samples from 29 enrolled
      patients. Changes in IGF and glucose homeostasis pathways were compared to
      control samples from patients in a concurrent clinical trial of neoadjuvant ADT
      alone. RESULTS: Significant increases were seen in GH (P = .001), IGF-I (P <
      .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide
      (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone.
      IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P =
      .001). No significant changes in blood glucose were evident. Patients with BMIs
      in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5)
      levels compared to overweight and obese patients. CONCLUSIONS: Patients with IGF
      IR blockade in combination with ADT demonstrated significant changes in IGF and
      glucose homeostasis pathway factors compared to patients receiving ADT alone. In
      the patients receiving combination therapy, patients with normal BMI had serum
      levels of glucose homeostasis components similar to individuals in the ADT-alone
      cohort, whereas patients with overweight and obese BMIs had serum levels that
      differed from the ADT cohort.

PMID- 23533232
TI  - Optimal macronutrient content of the diet for adolescents with prediabetes;
      RESIST a randomised control trial.
AB  - CONTEXT: Prediabetes and clinical insulin resistance in adolescents are rapidly
      emerging clinical problems with serious health outcomes. OBJECTIVE: The objective
      of this study was to determine the efficacy of 2 structured lifestyle
      interventions, both differing in diet macronutrient composition, on insulin
      sensitivity. DESIGN: This study was a randomized controlled trial, known as
      Researching Effective Strategies to Improve Insulin Sensitivity in Children and
      Teenagers, in 2 hospitals in Sydney, Australia. PARTICIPANTS: Participants
      included overweight or obese 10- to 17-year-olds with either prediabetes and/or
      clinical features of insulin resistance. INTERVENTION: At baseline adolescents
      were prescribed metformin and randomized to a structured diet, which was either
      high carbohydrate or moderate carbohydrate with increased protein. The program
      commenced with a 3-month dietary intervention, with the addition of an exercise
      intervention in the next 3 months. OUTCOMES: The outcomes included an insulin
      sensitivity, anthropometry, and cardiometabolic profile at 6 months. RESULTS: One
      hundred eleven subjects (66 girls) were recruited and 98 subjects (58 girls)
      completed the 6-month intervention. After 3 months the mean insulin sensitivity
      index increased by 0.3 [95% confidence interval (CI) 0.2-0.4]. After 6 months the
      mean insulin (picomoles per liter) to glucose ratio (millimoles per liter)
      decreased by 7.2 [95%CI -12.0 to -2.3], body mass index, expressed as a
      percentage of the 95th centile, decreased by 9% (95% CI -3 to -15), but there was
      no significant change in the lipids. There were no significant differences in
      outcomes between the diet groups at any time point. CONCLUSIONS: These results
      are in contrast with our hypothesis that adolescents randomized to the increased
      protein diet would have better outcomes. Further strategies are required to
      better address prediabetes and clinical features of insulin resistance in
      adolescents.

PMID- 23533233
TI  - Clinical outcomes and molecular profile of differentiated thyroid cancers with
      radioiodine-avid distant metastases.
AB  - BACKGROUND: Radioiodine (RAI) remains the mainstay of therapy for RAI-avid (RAIA)
      distant metastatic thyroid carcinoma. We previously demonstrated that RAI
      refractory distant metastatic thyroid cancers commonly harbor BRAF mutations.
      However, the molecular profile of RAIA metastatic thyroid cancer is unknown. Here
      we describe the mutational profile of thyroid tumors from follicular cell-derived
      cancer (FCDTC) patients presenting with RAIA distant metastases. In addition, we
      aimed to correlate clinical outcomes of RAI therapy with clinicopathological
      factors and tumor mutational status. METHODS: We retrospectively identified 43
      patients with FCDTC who had RAI uptake in the lungs and/or bones on their initial
      131I postablation scan. Primary tumors were genotyped for known mutations in
      thyroid cancer genes. Structural response to RAI was assessed 6-18 months after
      each administered RAI activity and at the end of follow-up. RESULTS: RAS, BRAF,
      RET/PTC, and PIK3CA mutations were found in 42, 23, 10, and 2% of tumors,
      respectively, and the remaining 23% were wild type. None of these patients
      achieved cure after repeat RAI therapies, and most patients (54%) experienced
      disease progression despite repeated RAI administration. There was an increased
      prevalence of RAS mutations in these RAIA tumors. RAS-mutant cancers were more
      likely to concentrate iodine on diagnostic whole body scans. Despite this,
      structural response to RAI was not influenced by tumor genotype. CONCLUSIONS:
      RAIA metastatic FCDTC are overrepresented with RAS mutations, whereas RAI
      refractory metastatic thyroid cancers are enriched with BRAF mutations. Despite a
      seemingly preserved ability to concentrate iodine, RAI therapy is ineffective in
      achieving cure in most patients with RAIA metastatic FCDTC, even in RAS-mutant
      disease. These poor outcomes may be improved based on recent evidence that
      pretreatment with MAPK kinase 1/2 inhibitors enhances responses to RAI,
      particularly in patients with RAS-mutant tumors.

PMID- 23533234
TI  - Childhood stunting and mortality between 36 and 64 years: the British 1946 Birth
      Cohort Study.
AB  - BACKGROUND: Our aim was to examine the associations between childhood or adult
      height and adult mortality. METHODS: In the prospective British 1946 Birth Cohort
      Study, childhood height was measured at 2, 4, 6, 7, 11, and 15 years, and adult
      height was measured at 36 years. Deaths were reported from the national health
      service register. RESULTS: A total of 3877 study members (1963 male) contributed
      106,333 person-years of follow-up; 391 deaths (228 male) were reported between
      the ages of 36 and 64 years. The strongest sex-adjusted association between
      height and mortality between ages 36 and 64 years was seen for height at age 6
      years. The association was nonlinear; only study members in the shortest quintile
      at 6 years had a higher relative risk of adult mortality compared with those in
      the tallest quintile. By contemporary growth standards, 5.7% (n = 188) had
      heights at 6 years less than the second percentile, and a further 15.0% (n = 490)
      had heights between the second to ninth percentiles; these groups had higher
      adult mortality than all other study members (hazard ratio, 2.18; 95% confidence
      interval, 1.52-3.13; P < .001; and hazard ratio, 1.42; 95% confidence interval,
      1.08-1.88; P = .01, respectively). Several determinants of childhood stunting
      (height at 6 years less than the second percentile) were directly associated with
      adult mortality; these included shorter parental heights and adverse early life
      nutrition and housing. CONCLUSIONS: British men and women born in 1946 were
      relatively stunted as children by contemporary standards. Those who were short at
      age 6 years had substantially higher mortality 30 to 60 years later. Furthermore,
      they accounted for the well-recognized inverse association between adult height
      and mortality.

PMID- 23533235
TI  - Allele percentage of the BRAF V600E mutation in papillary thyroid carcinomas and
      corresponding lymph node metastases: no evidence for a role in tumor progression.
AB  - CONTEXT: The relevance of the BRAF V600E mutation in papillary thyroid carcinoma
      (PTC) as a negative prognostic factor is a subject of intense debate. This
      mutation has been associated with several clinicopathological features, but the
      lack of consistency among data does not support its usefulness as marker of tumor
      aggressiveness and poorer outcome. Due to the genetic heterogeneity of the tumor,
      both the occurrence and the allele percentage of the BRAF mutation should be
      considered to unravel this controversy. OBJECTIVE: We aimed to evaluate the
      impact of the BRAF V600E mutation occurrence and the allele percentage on the
      metastatic process in PTCs. STUDY DESIGN: The presence and allele percentage of
      the BRAF mutation were determined by pyrosequencing in 132 cases of well
      differentiated PTCs with (n = 37) or without lymph node metastases (LNMs) (n =
      95) and in 40 LNMs matched with 35 PTCs. RESULTS: No significant differences were
      observed in either the occurrence or the allele percentage of V600E mutation
      between the 2 groups of PTCs with or without LNMs. The LNMs were heterogeneous
      for the V600E mutation as the primary lesions. CONCLUSIONS: In this study, the
      occurrence and percentage of the BRAF V600E mutated allele was not preferentially
      associated with the development of metastases and the average mutated allele
      percentage decreased as the tumor progresses from the primary site to the lymph
      node metastatic sites. These observations support the need to reevaluate the role
      of the BRAF V600E mutation as a negative prognostic marker in PTCs.

PMID- 23533236
TI  - Tumoral calcinosis in a patient on peritoneal dialysis.

PMID- 23533237
TI  - An exceptional false-positive finding in the postsurgical I 131 whole body scan
      of a differentiated thyroid carcinoma caused by an extralobar pulmonary
      sequestration.

PMID- 23533238
TI  - Clinical review: Bariatric surgery following treatment for craniopharyngioma: a
      systematic review and individual-level data meta-analysis.
AB  - OBJECTIVES: Craniopharyngiomas are rare low-grade tumors located in the
      hypothalamic and/or pituitary region. Hypothalamic involvement and treatment
      resulting in hypothalamic damage are known to lead to development of
      "hypothalamic obesity" (HyOb) in 50% of cases. The management of HyOb, associated
      with eating disorders and rapid comorbidities, is an important issue. Bariatric
      surgery is the most effective therapy for weight loss in patients with severe
      exogenous obesity. The aim of this systematic review and meta-analysis was to
      determine the 12-month outcome of bariatric surgery for HyOb due to
      craniopharyngioma treatment. METHODS AND RESULTS: Relevant studies were
      identified by searches of the MEDLINE and EMBASE databases until January 2013. A
      total of 21 cases were included: 6 with adjustable gastric banding, 8 with sleeve
      gastrectomy, 6 with Roux-en-Y gastric bypass, and 1 with biliopancreatic
      diversion. After data pooling, mean weight difference was -20.9 kg after 6 months
      (95% confidence interval [CI], -35.4, -6.3) and -15.1 kg after 12 months (95% CI,
      -31.7, +1.4). The maximal mean weight loss was achieved by the gastric bypass
      group: -31.0 kg (95% CI, -77.5, +15.5) and -33.7 kg (95% CI, -80.7, +13.3) after
      6 and 12 months, respectively. CONCLUSIONS: In this largest ever published study
      on the effect of bariatric surgery on obesity after craniopharyngioma treatment,
      we observed an important weight loss after 1 year of follow-up. Larger studies
      are warranted to establish appropriate selection criteria and the best surgical
      technique to perform bariatric surgery.

PMID- 23533239
TI  - Vitamin D levels for preventing acute coronary syndrome and mortality: evidence
      of a nonlinear association.
AB  - CONTEXT: Low serum calcidiol has been associated with multiple comorbidities and
      mortality but no "safe" range has been found for the upper concentration.
      OBJECTIVE: We aim to establish the upper threshold of serum calcidiol, beyond
      which there is an increased risk for acute coronary syndrome and/or mortality.
      DESIGN, SETTING, AND PARTICIPANTS: We extracted data for 1,282,822 Clalit Health
      Services members aged >45 between July 2007 and December 2011. Records of
      mortality or acute coronary syndrome were extracted during the follow-up period.
      Kaplan-Meier analysis calculated time to episode and Cox regression models
      generated adjusted hazard ratios for episode by calcidiol group (<10, 10.1-20,
      20.1-36, and >36.1 ng/mL). OUTCOME MEASURES: Acute coronary syndrome subsuming
      all-cause mortality. RESULTS: During the 54-month study period, 422,822 Clalit
      Health Services members were tested for calcidiol, of which 12,280 died of any
      cause (905 with acute coronary syndrome) and 3933 were diagnosed with acute
      coronary syndrome. Compared to those with 20-36 ng/mL, the adjusted hazard ratios
      among those with levels of <10, 10-20, and >36 ng/mL were 1.88 (confidence
      interval [CI]: 1.80-1.96), 1.25 (CI: 1.21-1.30), and 1.13 (CI: 1.04-1.22) (P <
      .05), respectively. LIMITATIONS: The study cohort comprised only 30% of the
      population, those tested for vitamin D. The small sample size of those with
      calcidiol >36 ng/mL prevented further analysis of this group. CONCLUSIONS:
      Vitamin D in the 20-36 ng/mL range was associated with the lowest risk for
      mortality and morbidity. The hazard ratio below and above this range increases
      significantly.

PMID- 23533241
TI  - Multisystem morbidity and mortality in Cushing's syndrome: a cohort study.
AB  - CONTEXT: Cushing's syndrome (CS) is associated with hypercoagulability, insulin
      resistance, hypertension, bone loss, and immunosuppression. To date, no
      adequately large cohort study has been performed to assess the multisystem
      effects of CS. OBJECTIVE: We aimed to examine the risks for mortality,
      cardiovascular disease, fractures, peptic ulcers, and infections in CS patients
      before and after treatment. DESIGN: Population-based cohort study. SETTING:
      Source population was the entire population of Denmark (1980 to 2010). Data were
      obtained from the Danish National Registry of Patients and the Danish Civil
      Registration System. PATIENTS: Benign CS of adrenal or pituitary origin and a
      matched population comparison cohort were included. OUTCOME MEASURES: We used Cox
      regression, and computed hazard ratios (HR) with 95% confidence intervals (95%
      CI). Morbidity was investigated in the 3 years before diagnosis; morbidity and
      mortality were assessed during complete follow-up after diagnosis and treatment.
      RESULTS: Included were 343 CS patients and 34 300 controls. Mortality was twice
      as high in CS patients (HR 2.3, 95%CI 1.8-2.9) compared with controls. Patients
      with CS were at increased risk for venous thromboembolism (HR 2.6, 95%CI 1.5
      4.7), myocardial infarction (HR 3.7, 95%CI 2.4-5.5), stroke (HR 2.0, 95%CI 1.3
      3.2), peptic ulcers (HR 2.0, 95%CI 1.1-3.6), fractures (HR 1.4, 95%CI 1.0-1.9),
      and infections (HR 4.9, 95%CI 3.7-6.4). This increased multimorbidity risk was
      present before diagnosis. Mortality and risk of myocardial infarction remained
      elevated during long-term follow-up. Mortality and risks for acute myocardial
      infarction, venous thromboembolism, stroke, and infections were similarly
      increased in adrenal and pituitary CS. CONCLUSIONS: Despite the apparently benign
      character of the disease, CS is associated with clearly increased mortality and
      multisystem morbidity, even before diagnosis and treatment.

PMID- 23533242
TI  - Relationship between serum 25-hydroxyvitamin D and lung function among Korean
      adults in Korea National Health and Nutrition Examination Survey (KNHANES), 2008
      2010.
AB  - CONTEXT: The relationship between vitamin D status and pulmonary function has not
      been investigated for an East Asian population. OBJECTIVE: The aim of the present
      study was to examine the relationship of serum 25-hydroxyvitamin D [25(OH)D] with
      lung function in Korean adults. DESIGN AND SETTING: The analysis used data from
      the Korea National Health and Nutrition Examination Survey (KNHANES), a cross
      sectional survey of Korean civilians, conducted from 2008 to 2010. PARTICIPANTS:
      A total of 10 096 people aged 19 years and older were selected from 16
      administrative districts in South Korea. MAIN OUTCOME MEASURES: Serum 25(OH)D
      levels with lung function [forced expiratory volume in 1 second (FEV1) and forced
      vital capacity (FVC)]. RESULTS: Serum 25(OH)D concentration was positively
      associated with lung function after controlling for age, sex, height, and season.
      For FEV1 and FVC, the differences between top and bottom quartiles in 25(OH)D
      were 51 mL (SE, 17 mL, P trend <.001) and 58 mL (SE, 20 mL, P trend <.005)
      greater volume, respectively. Association of serum 25(OH)D with FEV1 and FVC was
      only slightly attenuated after adjustment for body mass index, lifestyle and
      socioeconomic factors, and respiratory illness. The subjects with a history of
      pulmonary tuberculosis showed a much higher increase in FEV1; the difference
      between top and bottom quartiles in 25(OH)D was 229 mL (SE, 87 mL, P trend <.01).
      CONCLUSION: Serum 25(OH)D levels have a positive correlation with pulmonary
      function. This relationship appears prominent in subjects with susceptibility to
      pulmonary tuberculosis.

PMID- 23533240
TI  - Clinical review: The human experience with ghrelin administration.
AB  - CONTEXT: Ghrelin is an endogenous stimulator of GH and is implicated in a number
      of physiological processes. Clinical trials have been performed in a variety of
      patient populations, but there is no comprehensive review of the beneficial and
      adverse consequences of ghrelin administration to humans. EVIDENCE ACQUISITION:
      PubMed was utilized, and the reference list of each article was screened. We
      included 121 published articles in which ghrelin was administered to humans.
      EVIDENCE SYNTHESIS: Ghrelin has been administered as an infusion or a bolus in a
      variety of doses to 1850 study participants, including healthy participants and
      patients with obesity, prior gastrectomy, cancer, pituitary disease, diabetes
      mellitus, eating disorders, and other conditions. There is strong evidence that
      ghrelin stimulates appetite and increases circulating GH, ACTH, cortisol,
      prolactin, and glucose across varied patient populations. There is a paucity of
      evidence regarding the effects of ghrelin on LH, FSH, TSH, insulin, lipolysis,
      body composition, cardiac function, pulmonary function, the vasculature, and
      sleep. Adverse effects occurred in 20% of participants, with a predominance of
      flushing and gastric rumbles and a mild degree of severity. The few serious
      adverse events occurred in patients with advanced illness and were not clearly
      attributable to ghrelin. Route of administration may affect the pattern of
      adverse effects. CONCLUSIONS: Existing literature supports the short-term safety
      of ghrelin administration and its efficacy as an appetite stimulant in diverse
      patient populations. There is some evidence to suggest that ghrelin has wider
      ranging therapeutic effects, although these areas require further investigation.

PMID- 23533243
TI  - Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients
      with pseudohypoparathyroidism.
AB  - CONTEXT: Recent advances in genetics and epigenetics have revealed an overlap
      between molecular and clinical features of pseudohypoparathyroidism (PHP)
      subtypes, broadening the previous spectrum of PHP genotype-phenotype correlations
      and indicating limitations of the current classification of the disease.
      OBJECTIVES: The aim of the study was to screen patients with clinical diagnoses
      of PHP type I or pseudo-PHP for underlying molecular defects and explore possible
      correlations between molecular findings and clinical features. PATIENTS AND
      METHODS: We investigated the GNAS locus at the molecular level in 72 affected
      patients (46 women and 26 men) from 56 nonrelated families. Clinical data were
      obtained for 63 of these patients (38 women and 25 men). RESULTS: The molecular
      analysis showed that 35 patients carried structural mutations, 32 had loss of
      methylation, and 2 had a 2q37 deletion but did not reveal any (epi)mutation for 3
      patients. Comparing these results and the clinical data, we observed that a
      younger age at diagnosis was associated with structural defects at the GNAS gene
      and epigenetic defects with a diagnosis later in life (9.19 +/- 1.64 vs 24.57 +/-
      2.28 years, P < .0001). CONCLUSIONS: This first global review of PHP in Spain
      highlights the importance of a detailed clinical and genetic study of each
      patient and the integrated analysis of the findings from the two approaches. It
      may also help geneticists and clinicians to raise the suspicion of PHP earlier,
      reach more accurate diagnoses, and provide patients with PHP and their families
      with useful genetic information and counseling, thereby improving outcomes and
      quality of life.

PMID- 23533244
TI  - Methane and hydrogen positivity on breath test is associated with greater body
      mass index and body fat.
AB  - CONTEXT: Colonization of the gastrointestinal tract with methanogenic archaea
      (methanogens) significantly affects host metabolism and weight gain in animal
      models, and breath methane is associated with a greater body mass index (BMI)
      among obese human subjects. OBJECTIVE: The objective of the study was to
      characterize the relationship between methane and hydrogen on breath test (as a
      surrogate for colonization with the hydrogen requiring methanogen,
      Methanobrevibacter smithii), body weight, and percent body fat in a general
      population cohort. DESIGN AND SUBJECTS: This was a prospective study (n = 792) of
      consecutive subjects presenting for breath testing. SETTING: The study was
      conducted at a tertiary care center. OUTCOME MEASUREMENTS: BMI and percent body
      fat were measured. RESULTS: Subjects were classified into 4 groups based on
      breath testing: normal (N) (methane <3 ppm and hydrogen <20 ppm at or before 90
      minutes); hydrogen positive only (H+) [methane <3 ppm and hydrogen >=20 ppm);
      methane positive only (M+) (methane >=3 ppm and hydrogen <20 ppm), or methane and
      hydrogen positive (M+/H+) (methane >=3 ppm and hydrogen >=20 ppm]. There were
      significant differences in age but not in gender across the groups. After
      controlling for age as a confounding variable, M+/H+ subjects had significantly
      higher BMI than other groups (N: 24.1 +/- 5.2 kg/m(2); H+: 24.2 +/- 4.5 kg/m(2);
      M+: 24.0 +/- 3.75 kg/m(2); M+/H+: 26.5 +/- 7.1 kg/m(2), P < .02) and also had
      significantly higher percent body fat (N: 28.3 +/- 10.0%; H+: 27.5 +/- 9.0%; M+:
      28.0 +/- 8.9%; M+/H+; 34.1 +/- 10.9%, P < .001). CONCLUSIONS: The presence of
      both methane and hydrogen on breath testing is associated with increased BMI and
      percent body fat in humans. We hypothesize that this is due to colonization with
      the hydrogen-requiring M smithii, which affects nutrient availability for the
      host and may contribute to weight gain.

PMID- 23533245
TI  - Predicting the timeline to the final menstrual period: the study of women's
      health across the nation.
AB  - CONTEXT: Predicting the final menstrual period (FMP) would help women know when
      their menopause transition will be completed. Additionally, biological changes,
      such as accelerated bone loss, precede the FMP by at least 1 year. OBJECTIVE: Our
      objective was to assess whether FSH, estradiol, or urinary N-telopeptide predict
      where an individual is on her timeline to FMP. METHODS: The sample was 554 women
      from the Study of Women's Health Across the Nation. We modeled the probability of
      having crossed specified landmarks: 2 years before, 1 year before, and the FMP.
      We also modeled the probability of being in narrower intervals: 2 to1 year before
      FMP, 2 years before FMP and FMP, or 1 year before FMP and FMP. We determined the
      candidate markers that best predicted having crossed each landmark, with the
      optimum defined as the greatest area under the receiver-operator curve; created
      formulas for the probability of having crossed each landmark; and calculated
      sensitivity and specificity. RESULTS: Final models included current estradiol and
      FSH (each as a fraction of 1 previous reference measure), age, menopause
      transition stage, race/ethnicity, and whether serum was collected during the
      early follicular phase. Areas under the receiver-operator curves of final models
      that predicted the probability of a woman having crossed 2 years before, 1 year
      before, and the FMP itself were 0.902, 0.926, and 0.945, respectively. If we
      classified women as having crossed the 2 years before the FMP landmark when
      predicted probability exceeded 0.3, sensitivity was 85% and specificity 77%.
      CONCLUSION: This model could help patients and researchers estimate the time to
      FMP.

PMID- 23533248
TI  - Cardiac hormones for the treatment of cancer.
AB  - Four cardiac hormones, namely atrial natriuretic peptide, vessel dilator,
      kaliuretic peptide, and long-acting natriuretic peptide, reduce up to 97% of all
      cancer cells in vitro. These four cardiac hormones eliminate up to 86% of human
      small-cell lung carcinomas, two-thirds of human breast cancers, and up to 80% of
      human pancreatic adenocarcinomas growing in athymic mice. Their anticancer
      mechanisms of action, after binding to specific receptors on cancer cells,
      include targeting the rat sarcoma-bound GTP (RAS) (95% inhibition)-mitogen
      activated protein kinase kinase 1/2 (MEK 1/2) (98% inhibition)-extracellular
      signal-related kinase 1/2 (ERK 1/2) (96% inhibition) cascade in cancer cells.
      They also inhibit MAPK9, i.e. c-Jun N-terminal kinase 2. They are dual inhibitors
      of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89%).
      One of the downstream targets of VEGF is beta-catenin, which they reduce up to
      88%. The WNT pathway is inhibited up to 68% and secreted frizzled-related protein
      3 decreased up to 84% by the four cardiac hormones. AKT, a serine/threonine
      protein kinase, is reduced up to 64% by the cardiac hormones. STAT3, a final
      'switch' that activates gene expression that leads to malignancy, is decreased by
      up to 88% by the cardiac hormones. STAT3 is specifically decreased as they do not
      affect STAT1. There is a cross-talk between the RAS-MEK 1/2-ERK 1/2 kinase
      cascade, VEGF, beta-catenin, WNT, JNK, and STAT pathways and each of these
      pathways is inhibited by the cardiac hormones.

PMID- 23533247
TI  - TOP2A is overexpressed and is a therapeutic target for adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with no
      effective therapy for patients with unresectable disease. The aim of the current
      study was i) to evaluate TOP2A expression and function in human adrenocortical
      neoplasm and ACC cells and ii) to determine the anticancer activity of agents
      that target TOP2A. TOP2A mRNA and protein expression levels were evaluated in 112
      adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical
      tumors, and 11 ACCs). In vitro siRNA knockdown of TOP2A in ACC cell lines (NCI
      H295R and SW13) was used to determine its effect on cellular proliferation, cell
      cycle, anchorage-independent growth, and cellular invasion. We screened 14 TOP2A
      inhibitors for their anticancer activity in ACC cells. TOP2A mRNA and protein
      expression was significantly higher in ACC than in benign and normal
      adrenocortical tissue samples (P<0.05). Knockdown of TOP2A gene expression in ACC
      cell lines significantly decreased cell proliferation, anchorage-independent
      growth, and invasion (P<0.05). A screening assay in NCI-H295R cells showed that
      11 of 14 TOP2A inhibitors had antiproliferative activity, 5 of the 14 TOP2A
      inhibitors had a higher antiproliferative activity than mitotane, and aclarubicin
      was the agent with the highest activity. Aclarubicin was validated to
      significantly decrease proliferation and tumor spheroid size in both NCI-H295R
      and SW13 ACC cell lines (P<0.05). Our results suggest that TOP2A is overexpressed
      in ACC, regulates cellular proliferation and invasion in ACC cells, and is an
      attractive target for ACC therapy. Of the TOP2A inhibitors screened, aclarubicin
      is a good candidate agent to test in future clinical trials for patients with
      locally advanced and metastatic ACC.

PMID- 23533249
TI  - A bi-faceted role of estrogen receptor beta in breast cancer.
AB  - Despite over 15 years of research, the exact role, if any, played by estrogen
      receptor beta (ERbeta) in human breast cancer remains elusive. A large body of
      data both in vitro and in vivo supports its role as an antiproliferative, pro
      apoptotic factor especially when co-expressed with ERalpha. However, there is a
      smaller body of data associating ERbeta with growth and survival in breast
      cancer. In clinical studies and most often in cell culture studies, the pro
      growth and pro-survival activity of ERbeta occurs in ERalpha-negative breast
      cancer tissue and cells. This bi-faceted role of ERbeta is discussed in this
      review.

PMID- 23533246
TI  - In vivo and in vitro oncogenic effects of HIF2A mutations in pheochromocytomas
      and paragangliomas.
AB  - Pheochromocytomas and paragangliomas are highly vascular tumors of the autonomic
      nervous system. Germline mutations, including those in hypoxia-related genes,
      occur in one third of the cases, but somatic mutations are infrequent in these
      tumors. Using exome sequencing of six paired constitutive and tumor DNA from
      sporadic pheochromocytomas and paragangliomas, we identified a somatic mutation
      in the HIF2A (EPAS1) gene. Screening of an additional 239
      pheochromocytomas/paragangliomas uncovered three other HIF2A variants in sporadic
      (4/167, 2.3%) but not in hereditary tumors or controls. Three of the mutations
      involved proline 531, one of the two residues that controls HIF2alpha stability
      by hydroxylation. The fourth mutation, on Ser71, was adjacent to the DNA binding
      domain. No mutations were detected in the homologous regions of the HIF1A gene in
      132 tumors. Mutant HIF2A tumors had increased expression of HIF2alpha target
      genes, suggesting an activating effect of the mutations. Ectopically expressed
      HIF2alpha mutants in HEK293, renal cell carcinoma 786-0, or rat pheochromocytoma
      PC12 cell lines showed increased stability, resistance to VHL-mediated
      degradation, target induction, and reduced chromaffin cell differentiation.
      Furthermore, mice injected with cells expressing mutant HIF2A developed tumors,
      and those with Pro531Thr and Pro531Ser mutations had shorter latency than tumors
      from mice with wild-type HIF2A. Our results support a direct oncogenic role for
      HIF2A in human neoplasia and strengthen the link between hypoxic pathways and
      pheochromocytomas and paragangliomas.

PMID- 23533250
TI  - Role of glycogen synthase kinase-3beta in ketamine-induced developmental
      neuroapoptosis in rats.
AB  - BACKGROUND: Ketamine-induced neuroapoptosis has been attributed to diverse stress
      related mechanisms. Glycogen synthase kinase-3beta (GSK-3beta) is a
      multifunctional kinase that is active in neuronal development and linked to
      neurodegenerative disorders. We hypothesized that ketamine would enhance GSK
      3beta-induced neuroapopotosis, and that lithium, an inhibitor of GSK-3beta, would
      attenuate this response in vivo. METHODS: Protein levels of cleaved caspase-3,
      protein kinase B (AKT), GSK-3beta, and cyclin D1 were measured in post-natal day
      7 rat pups after 1.5, 3, 4.5, and 6 h exposure to ketamine. A cohort of rat pups
      was randomized to a 6 h exposure to ketamine with and without lithium.
      Neuroapoptosis was measured by cleaved caspase-3 and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labelling staining by immunohistochemistry.
      Protein levels of cleaved caspase-3 and -9 and the total and phosphorylated forms
      of AKT, GSK-3beta, and cyclin D1 (cell cycle protein) were also measured.
      RESULTS: Ketamine produced a duration-dependent increase in cleaved caspase-3 and
      cyclin D1, which corresponded to decreases in phosphorylated AKT and GSK-3beta.
      Co-administration of lithium with ketamine attenuated this response. CONCLUSIONS:
      Ketamine-induced neuroapoptosis is associated with a temporal decrease in GSK
      3beta phosphorylation, and simultaneous administration of lithium mitigated this
      response. These findings suggest that GSK-3beta is activated during this ketamine
      induced neuroapoptosis.

PMID- 23533251
TI  - General anaesthetics do not impair developmental expression of the KCC2 potassium
      chloride cotransporter in neonatal rats during the brain growth spurt.
AB  - BACKGROUND: The developmental transition from depolarizing to hyperpolarizing
      gamma-aminobutyric acid-mediated neurotransmission is primarily mediated by an
      increase in the amount of the potassium-chloride cotransporter KCC2 during early
      postnatal life. However, it is not known whether early neuronal activity plays a
      modulatory role in the expression of total KCC2 mRNA and protein in the immature
      brain. As general anaesthetics are powerful modulators of neuronal activity, the
      purpose of this study was to explore how these drugs affect KCC2 expression
      during the brain growth spurt. METHODS: Wistar rat pups were exposed to either a
      single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal
      days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting,
      immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3
      days post-exposure in the medial prefrontal cortex. RESULTS: There was a
      progressive and steep increase in the expression of KCC2 between birth and 2
      weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any
      investigated stages of the brain growth spurt did not influence the expression of
      this cotransporter protein. CONCLUSION: I.V. general anaesthetics do not seem to
      influence developmental expression of KCC2 during the brain growth spurt.

PMID- 23533252
TI  - Effect of concentration of local anaesthetic solution on the ED50 of bupivacaine
      for supraclavicular brachial plexus block.
AB  - BACKGROUND: The aim of this trial was to compare the effect of concentration of
      bupivacaine solution on the ED50 dose required for supraclavicular brachial
      plexus block. METHODS: Nineteen ASA I, II, or III patients of either sex
      undergoing elective upper limb surgery under ultrasound-guided supraclavicular
      brachial block were recruited in this double-blind, randomized trial which
      followed an up-and-down sequential allocation design. The patients were randomly
      allocated to three groups who then received 0.25%, 0.375%, or 0.5% bupivacaine.
      The study design and analysis followed Dixon's small sample model using a
      'nominal' sample size of six in each group. The data from previous research were
      used to guide the dose levels and dose intervals for the three groups. RESULTS:
      The median effective volume [95% confidence interval (CI)] for 0.25%, 0.375%, and
      0.5% bupivacaine for supraclavicular block was 26.8 (18.6-38.4), 18.1 (12.1
      26.0), and 12.0 (8.4-17.3) ml, respectively. The ED50 dose (95% CI) for 0.25%,
      0.375%, and 0.5% bupivacaine was 66.9 (46.6-96.0), 68.0 (47.4-97.6), and 60.1
      (41.8-86.3) mg, respectively. The difference in the ED50 dose between the three
      concentrations was not statistically significant. CONCLUSIONS: Our study
      demonstrates that the ED50 dose of bupivacaine for supraclavicular block is not
      dependent on the concentration. Lowering the concentration or the strength of the
      local anaesthetic leads to an increase in the volume required for successful
      block.

PMID- 23533253
TI  - Proof of concept evaluation of the electroencephalophone as a discriminator
      between wakefulness and general anaesthesia.
AB  - BACKGROUND: Depth of anaesthesia (DOA) monitors based on the electroencephalogram
      (EEG) are commonly used in anaesthetic practice. Their technology relies on
      mathematical analysis of the EEG waveform, generally resulting in a number which
      corresponds to anaesthetic depth. We have created a novel method of interpreting
      the EEG, which retains its underlying complexity. This method consists of turning
      the EEG into a sound: the electroencephalophone (EEP). METHODS: In a pilot study,
      we recorded awake and anaesthetized EEGs from six patients. We transformed each
      EEG into an audio signal using a ring buffer with a write frequency of 1 kHz and
      a read frequency of 48 kHz, thus elevating all output frequencies by a factor of
      48. In essence, the listener hears the previous 12 s of EEG data compressed into
      250 ms, updated every 250 ms. From these data, we generated a bank of 5 s audio
      clips, which were then used to train and test a sample of 23 anaesthetists.
      RESULTS: After training, 21 of the 23 anaesthetists were able to use the EEP to
      correctly identify the conscious state of >5 of 10 randomly selected patients
      (P<0.001). The median score was 8 out of 10, with an inter-quartile range of 7-9.
      CONCLUSIONS: The EEP shows promise as a DOA monitor. However, extensive
      validation would be required in a variety of clinical settings before it could be
      accepted into mainstream clinical practice.

PMID- 23533254
TI  - Analgesic and sympatholytic effects of low-dose intrathecal clonidine compared
      with bupivacaine: a dose-response study in female volunteers.
AB  - BACKGROUND: A wide range of doses has been suggested for intrathecal clonidine,
      but no dose-ranging study has examined analgesic effects below 100 ug. The
      primary aim of this volunteer study was to assess the dose vs analgesic effect
      relationship for doses of intrathecal clonidine below 100 ug. METHODS: After IRB
      approval and signed informed consent, 11 healthy female volunteers participated
      in this randomized, double-blinded, cross-over study using a dose-ranging sparse
      sampling technique. Participants received intrathecal clonidine (doses 0-100 ug;
      n=10) and intrathecal bupivacaine (doses 0-8.8 mg; n=9) on separate study days.
      At baseline, 30, and 60 min from drug administration, experimental heat pain
      tolerance was assessed at both a lumbar and a cranial dermatome. Heat and cold
      perception thresholds were assessed at the same time intervals. Heart rate (HR),
      arterial pressure, and forearm-finger and toe-leg cutaneous temperature gradients
      (Tfinger-arm and Ttoe-leg) were used as measures of sympatholysis. RESULTS: Both
      intrathecal clonidine and bupivacaine caused significant, dose-dependent
      analgesic effects at the leg but not the head. Significant analgesia to
      experimental heat pain was detected above 25 ug clonidine and 3 mg bupivacaine.
      Administration of bupivacaine but not clonidine resulted in a significant dose
      related decrease in HR and Ttoe-leg; neither drug caused dose-related
      sympatholytic effects in the doses used. CONCLUSIONS: After 50 ug clonidine or 5
      mg bupivacaine, the heat pain tolerance increased by ~1 degrees C, similar to the
      analgesic effect of 5 mg epidural morphine or 30 ug epidural fentanyl in previous
      studies using this experimental heat pain model. Our results provide additional
      data for rational dose selection of intrathecal clonidine.

PMID- 23533255
TI  - Effect of intrathecal magnesium in the presence or absence of local anaesthetic
      with and without lipophilic opioids: a systematic review and meta-analysis.
AB  - Spinal anaesthesia is the primary anaesthetic technique for many types of
      surgery. Adjuncts to the local anaesthetics (LA) used in spinal anaesthesia can
      exhibit undesirable side-effects, limiting their use, but magnesium may have
      advantages in this respect. We sought randomized control trials (RCTs) in
      patients undergoing all types of surgery and in women in labour to compare the
      effect of intrathecal magnesium sulphate +/- LA +/- lipophilic opioid
      (experimental group) with the use of either intrathecal lipophilic opioids +/- LA
      or LA only (control group). The primary outcome was the duration of spinal
      anaesthesia. Secondary outcomes were: onset and time to maximal sensory blockade,
      onset of motor block, and duration of sensory and motor blockade. We found 15
      RCTs comprising 980 patients. The duration of spinal anaesthesia was
      significantly increased in the experimental group [standardized mean difference
      (SMD) -1.05 (-1.70, -0.41) (P = 0.001)], compared with the control group. This
      increased duration of spinal anaesthesia was seen in non-obstetric studies, SMD 
      1.38 (-2.11, -0.66) (P = 0.0002), but not in obstetric studies, SMD -0.55 (-1.87,
      0.77) (P = 0.41). There was no delay in the onset of sensory or motor blockade.
      The incidence of hypotension and pruritus was similar in both groups.
      Heterogeneity was high in all outcome measures. The duration of spinal
      anaesthesia may be increased by the addition of magnesium to lipophilic opioids
      +/- LA.

PMID- 23533256
TI  - Positive end-expiratory pressure aggravates left ventricular diastolic relaxation
      further in patients with pre-existing relaxation abnormality.
AB  - BACKGROUND: Positive end-expiratory pressure (PEEP) has been known to adversely
      influence cardiac output. Even though left ventricular (LV) diastolic function
      significantly contributes to LV performance, the effects of PEEP on LV diastolic
      function remains controversial. We, therefore, aimed to examine the effects of
      PEEP on LV diastolic function by use of pulsed wave Doppler tissue imaging in
      patients with pre-existing LV relaxation abnormality. METHODS: Seventeen patients
      with peak early diastolic velocity of lateral mitral annulus (E') <8.5 cm s(-1)
      among patients who underwent coronary artery bypass graft surgery were evaluated.
      Echocardiographic and haemodynamic variables were measured with 0, 5, and 10
      cmH2O of PEEP. E' and deceleration time (DT) of peak early transmitral filling
      velocity (E) were used as echocardiographic indicators of LV diastolic function.
      RESULTS: Mean arterial blood pressure decreased during 10 cmH2O PEEP, compared
      with that during 0 cmH2O PEEP. E' showed a gradual and significant decrease with
      an incremental increase in PEEP (6.9 +/- 0.9, 5.8 +/- 0.9, and 5.2 +/- 1.2 cm s(
      1) during 0, 5, and 10 cmH2O PEEP, respectively), and DT of E was prolonged
      during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. CONCLUSIONS:
      Increasing PEEP led to a progressive decline in LV relaxation in patients with
      pre-existing LV relaxation abnormality.

PMID- 23533257
TI  - Sarcomatoid carcinoma represents a complete phenotype with various pathways of
      epithelial mesenchymal transition.
AB  - AIMS: Sarcomatoid carcinoma (SC) is considered to be a result of the sarcomatoid
      change of epithelial carcinoma. However, epithelial-mesenchymal transition (EMT)
      in SC has been insufficiently studied. METHODS: We evaluated the expression
      patterns of EMT-related phenotypic markers with transcription factors in 27 SCs
      originating from various organs, and we investigated the phenotypic
      characteristics of SCs classified as complete, incomplete or wild-type. We
      further analysed correlations between EMT-related phenotype markers and
      transcription factors. RESULTS: Epithelial markers (E-cadherin, claudin-3 and
      claudin-4) were consistently down-regulated, whereas mesenchymal markers (S100A4,
      alpha-smooth muscle actin (SMA), vimentin, PDGFRalpha and beta-catenin) were
      variously expressed except for vimentin. EMT-related transcription factors (SIP1,
      Snail1, Slug, Twist1, ZEP1 and Oct-4) also showed various expression patterns.
      The expression patterns of phenotypic markers showed that most SCs (22/27, 81.5%,
      95% CI 65.8 to 97.1%) had complete EMT phenotypes, whereas the remaining 5
      (18.5%, 95% CI 2.8 to 24.1%) were of incomplete type. Unsupervised hierarchical
      clustering analysis revealed that SCs were clustered into several subgroups by
      EMT-related protein expression pattern. Twist1 positivity was significantly
      concordant with alpha-SMA positivity (kappa value: 0.908; 95% CI 0.73 to 1.00,
      p<0.001, adjusted p<0.001). The EMT phenotypes of SC were simple, with complete
      phenotype being the predominant form, and the morphological changes of the SCs
      were also relevant in terms of EMT. CONCLUSIONS: SC seems to be an irreversible,
      permanent change in the EMT phenomenon, with complete EMT phenotypes and various
      EMT-related pathways being involved in SC.

PMID- 23533258
TI  - Myoepithelial and epithelial-myoepithelial, mesenchymal and fibroepithelial
      breast lesions: updates from the WHO Classification of Tumours of the Breast
      2012.
AB  - In the 4th edition of the WHO Classification of Tumours of the Breast,
      myoepithelial lesions are retitled myoepithelial and epithelial-myoepithelial
      lesions in order to better reflect the dual participation of luminal and
      myoepithelial compartments in some key entities. Malignant myoepithelioma,
      described as a section within the chapter on myoepithelial lesions in the 3rd
      edition, is recognised in the 4th edition as part of metaplastic carcinoma.
      Adenomyoepithelioma with malignancy is categorised in terms of the cellular
      component undergoing malignant transformation. The list of antibodies that can be
      used for identifying myoepithelial cells is updated. Among mesenchymal lesions,
      new additions are nodular fasciitis and atypical vascular lesions, while the
      haemangiopericytoma is removed. The 3rd edition stated that pathological
      prediction of behaviour of phyllodes tumours is difficult in the individual case.
      In the 4th edition, some progress has been made in prioritisation and weighting
      of histological parameters that can potentially estimate probability of
      recurrence. The WHO Working Group advocates leaning towards a diagnosis of
      fibroadenoma in cases where there is histological uncertainty in distinction from
      a benign phyllodes tumour, or adopting the neutral term 'benign fibroepithelial
      neoplasm', as the clinical behaviour of fibroadenoma overlaps with that of benign
      phyllodes tumour. The 3rd edition terminology of 'periductal stromal sarcoma' is
      revised to 'periductal stromal tumour', akin to the widespread consensus to avoid
      the use of the term 'cystosarcoma' in the context of phyllodes tumours.

PMID- 23533259
TI  - Molecular determinations of EGFR and EML4-ALK on a single slide of NSCLC tissue.
AB  - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) and anti-anaplastic lymphoma
      kinase (ALK) agents are highly effective for the treatment of non-small cell lung
      cancer (NSCLC) patients harbouring specific alterations, and molecular
      characterisation of the tumour is needed even when limited tumour material is
      available. METHODS: 20 patients with a known epidermal growth factor receptor
      (EGFR) gene status were enrolled: 10 had mutated and 10 had wild type tumours.
      FISH analysis was performed on one cytological or histological sample to
      determine EML4-ALK status, after which the same cells scraped off each slide were
      used to evaluate the EGFR status. RESULTS: In the 10 EGFR mutated patients,
      molecular analysis showed the same results as those obtained before the FISH
      test. One patient with an EGFR mutation also showed an EML4-ALK translocation,
      and both FISH-positive and FISH-negative cells maintained the EGFR mutation.
      CONCLUSIONS: EGFR mutation analysis can be performed on the same sample
      previously submitted to the EML4-ALK FISH procedure.

PMID- 23533260
TI  - A simplified economic approach to thyroid FNA cytology and surgical intervention
      in thyroid nodules.
AB  - OBJECTIVE: Few studies have modelled the economics of thyroid FNA. METHODS: A
      simple spreadsheet economic model for delivery of thyroid fine needle aspiration
      (FNA) cytology is described using the UK Royal College of Pathologists'
      Classification for thyroid FNA which is based on The Bethesda System for
      Reporting Thyroid Cytopathology. RESULTS: We show an estimated 27.8% cost
      treatment reduction per patient if low rates of non-diagnostic for cytological
      diagnosis (Thy 1) and neoplasm possible atypia/non-diagnostic (Thy 3a) are
      achieved, which require rapid onsite FNA adequacy assessment of aspiration
      samples. If we assume that the number of thyroid FNAs performed in the UK
      annually is around 500 per million, and the UK population is 62 million, this
      could save the UK National Health Service significant sums, as the additional
      cost per patient treated in this model varies from L781 for a scenario with
      ultrasound guided FNA and inclinic cell adequacy assessment to L998 where
      aspirates are taken in conventional fashion without any inclinic adequacy
      assessment. CONCLUSIONS: This model makes a strong economic case for the
      introduction of rapid onsite assessment of thyroid FNA across cancer networks, to
      improve the diagnostic efficacy of thyroid FNA.

PMID- 23533261
TI  - Histochemical detection of platelet esterase activity in the bone marrow
      postmortem: can megakaryocytes serve as indicators for time since death?
AB  - AIMS: alpha-Naphthyl acetate esterase (ANAE) is one of the few enzymes that are
      histochemically detectable on formalin-fixed paraffin-embedded tissue. In bone
      marrow (BM) biopsies, ANAE staining highlights megakaryocytes. We investigated
      autopsy BM to determine whether ANAE staining intensity (SI) was associated with
      postmortem intervals (PMI, period between death and autopsy), and thus could
      allow the time of death of a patient to be deduced. METHODS: ANAE-stained BM
      slides of 74 forensic and pathology autopsies as well as 22 biopsies were
      histologically evaluated and their SIs semiquantitatively graded. RESULTS: ANAE
      SIs did not differ between men and women and slightly decreased with age.
      Biopsies had significantly higher ANAE-SIs than pathology cases. In autopsies,
      ANAE-SIs were not associated with PMI, except for cases with PMI >=7 days which
      were consistently ANAE-negative. CONCLUSIONS: ANAE-SIs in postmortem BM samples
      were independent of PMI. Thus, ANAE staining of BM megakaryocytes cannot serve as
      an indicator for time-since-death of a patient.

PMID- 23533262
TI  - Consultant leaders and delivery of high quality pathology services.

PMID- 23533263
TI  - De-repression of PDGFRbeta transcription promotes acquired resistance to EGFR
      tyrosine kinase inhibitors in glioblastoma patients.
AB  - Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major
      challenge for personalized cancer therapy. Multiple genetic mechanisms of
      acquired TKI resistance have been identified in several types of human cancer.
      However, the possibility that cancer cells may also evade treatment by co-opting
      physiologically regulated receptors has not been addressed. Here, we show the
      first example of this alternate mechanism in brain tumors by showing that EGF
      receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally
      de-repressing platelet-derived growth factor receptor beta (PDGFRbeta).
      Mechanistic studies show that EGFRvIII signaling actively suppresses PDGFRbeta
      transcription in an mTORC1- and extracellular signal-regulated kinase-dependent
      manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs
      dependent on the consequently de-repressed PDGFRbeta signaling for growth and
      survival. Importantly, combined inhibition of EGFR and PDGFRbeta signaling
      potently suppresses tumor growth in vivo. These data identify a novel, nongenetic
      TKI resistance mechanism in brain tumors and provide compelling rationale for
      combination therapy. SIGNIFICANCE: These results provide the fi rst clinical and
      biologic evidence for receptor tyrosinekinase (RTK) "switching" as a mechanism of
      resistance to EGFR inhibitors in GBM and provide a molecular explanation of how
      tumors can become "addicted" to a non amplified, nonmutated, physiologically
      regulated RTK to evade targeted treatment.

PMID- 23533264
TI  - Response to Cabozantinib in patients with RET fusion-positive lung
      adenocarcinomas.
AB  - The discovery of RET fusions in lung cancers has uncovered a new therapeutic
      target for patients whose tumors harbor these changes. In an unselected
      population of non-small cell lung carcinomas (NSCLCs), RET fusions are present in
      1% to 2% of cases. This incidence increases substantially, however, in never
      smokers with lung adenocarcinomas that lack other known driver oncogenes.
      Although preclinical data provide experimental support for the use of RET
      inhibitors in the treatment of RET fusion-positive tumors, clinical data on
      response are lacking. We report preliminary data for the first three patients
      treated with the RET inhibitor cabozantinib on a prospective phase II trial for
      patients with RET fusion-positive NSCLCs (NCT01639508). Confirmed partial
      responses were observed in 2 patients, including one harboring a novel TRIM33-RET
      fusion. A third patient with a KIF5B-RET fusion has had prolonged stable disease
      approaching 8 months (31 weeks). All three patients remain progression-free on
      treatment.

PMID- 23533265
TI  - Targeted inhibition of the molecular chaperone Hsp90 overcomes ALK inhibitor
      resistance in non-small cell lung cancer.
AB  - EML4-ALK gene rearrangements define a unique subset of patients with non-small
      cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma
      kinase (ALK) inhibitor crizotinib in this population has become a paradigm for
      molecularly targeted therapy. Here, we show that the Hsp90 inhibitor ganetespib
      induced loss of EML4-ALK expression and depletion of multiple oncogenic signaling
      proteins in ALK-driven NSCLC cells, leading to greater in vitro potency, superior
      antitumor efficacy, and prolonged animal survival compared with results obtained
      with crizotinib. In addition, combinatorial benefit was seen when ganetespib was
      used with other targeted ALK agents both in vitro and in vivo. Importantly,
      ganetespib overcame multiple forms of crizotinib resistance, including secondary
      ALK mutations, consistent with activity seen in a patient with crizotinib
      resistant NSCLC. Cancer cells driven by ALK amplification and oncogenic
      rearrangements of ROS1 and RET kinase genes were also sensitive to ganetespib
      exposure. Taken together, these results highlight the therapeutic potential of
      ganetespib for ALK-driven NSCLC. SIGNIFICANCE: In addition to direct kinase
      inhibition, pharmacologic blockade of the molecular chaperone Hsp90 is emerging
      as a promising approach for treating tumors driven by oncogenic rearrangements of
      ALK. The bioactivity profi le of ganetespib presented here underscores a new
      therapeutic opportunity to target ALK and overcome multiple mechanisms of
      resistance in patients with ALK-positive NSCLC.

PMID- 23533267
TI  - Why residents of Dutch deprived neighbourhoods are less likely to be heavy
      drinkers: the role of individual and contextual characteristics.
AB  - BACKGROUND: Earlier research has shown that residents of Dutch deprived
      neighbourhoods drink less alcohol than people in other areas. We aimed to assess
      the role of individual and neighbourhood characteristics in a cross-sectional,
      nationwide, multilevel study. METHODS: Individual data of 30,117 Dutch adults,
      living in 1722 neighbourhoods across the Netherlands, were obtained from the 2004
      to 2009 national health survey (POLS). Chronic heavy alcohol consumption was
      measured as >=14 drinks/week for women and >=21 for men, and episodic heavy
      drinking as >=6 drinks/day at least once a week. Neighbourhood deprivation was
      dichotomous; deprived districts as selected by the Dutch government versus other
      areas. Multilevel logistic regression models of the association between
      deprivation and heavy drinking were corrected for age, gender, household
      composition, population density and potential predictors ethnicity, socioeconomic
      status (education, income), neighbourhood-level social cohesion and percentage
      Muslims. RESULTS: The prevalence of heavy drinking was lower in deprived
      neighbourhoods than in the rest of the Netherlands. This association was found
      for both chronic and episodic heavy drinking (OR=0.58 (0.47 to 0.72) and OR=0.57
      (0.45 to 0.72), respectively). Adding ethnicity to the model reduced these
      associations by approximately one half. Socioeconomic composition did not
      contribute to the relationship. The proportion of Muslims explained a small part,
      while social cohesion explained even less of the association. Stronger
      associations were observed for women and older adults than for men and younger
      adults. CONCLUSIONS: The lower prevalence of heavy drinking occurring in deprived
      areas is largely explained by the ethnicity of neighbourhood residents.

PMID- 23533268
TI  - Kickstart your research.

PMID- 23533266
TI  - Safe drug use in long QT syndrome and Brugada syndrome: comparison of website
      statistics.
AB  - AIMS: We sought to obtain insights into the efficacy of two websites,
      www.QTdrugs.org and www.BrugadaDrugs.org, that have the intention to prevent
      fatal arrhythmias due to unsafe drug use in Long QT syndrome and Brugada
      syndrome. METHODS AND RESULTS: Prospective web-use statistical analysis combined
      with online surveys were employed. Our main outcome measure was the percentage of
      Long QT syndrome patients and Brugada syndrome patients reporting refraining or
      discontinuation of possible unsafe drugs. QTdrugs.org has received >3 100 000
      visitors from 180 countries. Most visitors originated from the Americas (87%), as
      compared with Europe (7%), Asia (3%), Oceania (2%), and Africa (1%). The
      QTdrugs.org survey yielded 340 respondents: 34% were patients and 50% medical
      professionals. Of the patients, 79% reported that they refrained from, and 61%
      reported discontinuing drugs due to the website. The website was very much
      appreciated by 65% of the respondents and 30% found it rather helpful. The
      BrugadaDrugs.org received >48 000 visitors from 154 countries. Most visitors
      originated from Europe (46%) and the Americas (39%), but less from Asia (10%),
      Oceania (4%), and Africa (<1%). The BrugadaDrugs.org survey yielded 178
      respondents: 68% were patients and 21% medical professionals. Of the patients,
      72% reported refraining from, and 48% discontinuing drugs due to the website. The
      website was very much appreciated by 72% of the respondents and 25% found it
      rather helpful. CONCLUSION: These websites are extensively used, they promote
      drug awareness, and they help patients to avoid possible pro-arrhythmic drugs.
      Visitors find the websites valuable but should note their limitations.

PMID- 23533269
TI  - Illustrating the oceans.

PMID- 23533270
TI  - Circulating tumor cells.

PMID- 23533272
TI  - Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase
      fusions characterizing pediatric astrocytomas.
AB  - Astrocytomas are the most common type of brain tumors in children. Activated BRAF
      protein kinase mutations are characteristic of pediatric astrocytomas with
      KIAA1549-BRAF fusion genes typifying low-grade astrocytomas and (V600E)BRAF
      alterations characterizing distinct or higher-grade tumors. Recently, BRAF
      targeted therapies, such as vemurafenib, have shown great promise in treating
      V600E-dependent melanomas. Like (V600E)BRAF, BRAF fusion kinases activate MAPK
      signaling and are sufficient for malignant transformation; however, here we
      characterized the distinct mechanisms of action of KIAA1549-BRAF and its
      differential responsiveness to PLX4720, a first-generation BRAF inhibitor and
      research analog of vemurafenib. We found that in cells expressing KIAA1549-BRAF,
      the fusion kinase functions as a homodimer that is resistant to PLX4720 and
      accordingly is associated with CRAF-independent paradoxical activation of MAPK
      signaling. Mutagenesis studies demonstrated that KIAA1549-BRAF fusion-mediated
      signaling is diminished with disruption of the BRAF kinase dimer interface. In
      addition, the KIAA1549-BRAF fusion displays increased binding affinity to kinase
      suppressor of RAS (KSR), an RAF relative recently demonstrated to facilitate MEK
      phosphorylation by BRAF. Despite its resistance to PLX4720, the KIAA1549-BRAF
      fusion is responsive to a second-generation selective BRAF inhibitor that, unlike
      vemurafenib, does not induce activation of wild-type BRAF. Our data support the
      development of targeted treatment paradigms for BRAF-altered pediatric
      astrocytomas and also demonstrate that therapies must be tailored to the specific
      mutational context and distinct mechanisms of action of the mutant kinase.

PMID- 23533273
TI  - Sparse dynamics for partial differential equations.
AB  - We investigate the approximate dynamics of several differential equations when
      the solutions are restricted to a sparse subset of a given basis. The restriction
      is enforced at every time step by simply applying soft thresholding to the
      coefficients of the basis approximation. By reducing or compressing the
      information needed to represent the solution at every step, only the essential
      dynamics are represented. In many cases, there are natural bases derived from the
      differential equations, which promote sparsity. We find that our method
      successfully reduces the dynamics of convection equations, diffusion equations,
      weak shocks, and vorticity equations with high-frequency source terms.

PMID- 23533274
TI  - TPL2 kinase is a suppressor of lung carcinogenesis.
AB  - Lung cancer is a heterogeneous disease at both clinical and molecular levels,
      posing conceptual and practical bottlenecks in defining key pathways affecting
      its initiation and progression. Molecules with a central role in lung
      carcinogenesis are likely to be targeted by multiple deregulated pathways and may
      have prognostic, predictive, and/or therapeutic value. Here, we report that Tumor
      Progression Locus 2 (TPL2), a kinase implicated in the regulation of innate and
      adaptive immune responses, fulfils a role as a suppressor of lung carcinogenesis
      and is subject to diverse genetic and epigenetic aberrations in lung cancer
      patients. We show that allelic imbalance at the TPL2 locus, up-regulation of
      microRNA-370, which targets TPL2 transcripts, and activated RAS (rat sarcoma)
      signaling may result in down-regulation of TPL2 expression. Low TPL2 levels
      correlate with reduced lung cancer patient survival and accelerated onset and
      multiplicity of urethane-induced lung tumors in mice. Mechanistically, TPL2 was
      found to antagonize oncogene-induced cell transformation and survival through a
      pathway involving p53 downstream of cJun N-terminal kinase (JNK) and be required
      for optimal p53 response to genotoxic stress. These results identify multiple
      oncogenic pathways leading to TPL2 deregulation and highlight its major tumor
      suppressing function in the lung.

PMID- 23533275
TI  - Development and validation of a 32-gene prognostic index for prostate cancer
      progression.
AB  - The accurate determination of the risk of cancer recurrence is an important unmet
      need in the management of prostate cancer. Patients and physicians must weigh the
      benefits of currently available therapies against the potential morbidity of
      these treatments. Herein we describe the development of a gene expression-based
      continuous risk index and a validation of this test in an independent, blinded
      cohort of post-radical prostatectomy (RP) patients. A gene expression signature,
      prognostic for prostate-specific antigen (PSA) recurrence, was identified through
      a bioinformatic analysis of the expression of 1,536 genes in malignant prostate
      tissue from a training cohort of consecutive patients treated with RP. The assay
      was transferred to a real-time RT-PCR platform, and a continuous risk index model
      was constructed based on the expression of 32 genes. This 32-gene risk index
      model was validated in an independent, blinded cohort of 270 RP patients. In
      multivariate analyses, the risk index was prognostic for risk of PSA recurrence
      and had added value over standard prognostic markers such as Gleason score,
      pathologic tumor stage, surgical margin status, and presurgery PSA (hazard ratio,
      4.05; 95% confidence interval, 1.50-10.94; P = 0.0057). Furthermore, RP patients
      could be stratified based on the risk of PSA recurrence and the development of
      metastatic disease. The 32-gene signature identified here is a robust prognostic
      marker for disease recurrence. This assay may aid in postoperative treatment
      selection and has the potential to impact decision making at the biopsy stage.

PMID- 23533276
TI  - Transposon mutagenesis reveals cooperation of ETS family transcription factors
      with signaling pathways in erythro-megakaryocytic leukemia.
AB  - To define genetic lesions driving leukemia, we targeted cre-dependent Sleeping
      Beauty (SB) transposon mutagenesis to the blood-forming system using a
      hematopoietic-selective vav 1 oncogene (vav1) promoter. Leukemias of diverse
      lineages ensued, most commonly lymphoid leukemia and erythroleukemia. The
      inclusion of a transgenic allele of Janus kinase 2 (JAK2)V617F resulted in
      acceleration of transposon-driven disease and strong selection for
      erythroleukemic pathology with transformation of bipotential erythro
      megakaryocytic cells. The genes encoding the E-twenty-six (ETS) transcription
      factors Ets related gene (Erg) and Ets1 were the most common sites for transposon
      insertion in SB-induced JAK2V617F-positive erythroleukemias, present in 87.5% and
      65%, respectively, of independent leukemias examined. The role of activated Erg
      was validated by reproducing erythroleukemic pathology in mice transplanted with
      fetal liver cells expressing translocated in liposarcoma (TLS)-ERG, an activated
      form of ERG found in human leukemia. Via application of SB mutagenesis to TLS-ERG
      induced erythroid transformation, we identified multiple loci as likely
      collaborators with activation of Erg. Jak2 was identified as a common transposon
      insertion site in TLS-ERG-induced disease, strongly validating the cooperation
      between JAK2V617F and transposon insertion at the Erg locus in the JAK2V617F
      positive leukemias. Moreover, loci expressing other regulators of signal
      transduction pathways were conspicuous among the common transposon insertion
      sites in TLS-ERG-driven leukemia, suggesting that a key mechanism in
      erythroleukemia may be the collaboration of lesions disturbing erythroid
      maturation, most notably in genes of the ETS family, with mutations that reduce
      dependence on exogenous signals.

PMID- 23533278
TI  - An oculomotor continuum from exploration to fixation.
AB  - During visual exploration, saccadic eye movements scan the scene for objects of
      interest. During attempted fixation, the eyes are relatively still but often
      produce microsaccades. Saccadic rates during exploration are higher than those of
      microsaccades during fixation, reinforcing the classic view that exploration and
      fixation are two distinct oculomotor behaviors. An alternative model is that
      fixation and exploration are not dichotomous, but are instead two extremes of a
      functional continuum. Here, we measured the eye movements of human observers as
      they either fixed their gaze on a small spot or scanned natural scenes of varying
      sizes. As scene size diminished, so did saccade rates, until they were continuous
      with microsaccadic rates during fixation. Other saccadic properties varied as
      function of image size as well, forming a continuum with microsaccadic parameters
      during fixation. This saccadic continuum extended to nonrestrictive, ecological
      viewing conditions that allowed all types of saccades and fixation positions. Eye
      movement simulations moreover showed that a single model of oculomotor behavior
      can explain the saccadic continuum from exploration to fixation, for images of
      all sizes. These findings challenge the view that exploration and fixation are
      dichotomous, suggesting instead that visual fixation is functionally equivalent
      to visual exploration on a spatially focused scale.

PMID- 23533279
TI  - Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in
      regulating acute responses to PTH.
AB  - Agonist-induced phosphorylation of the parathyroid hormone (PTH) receptor 1
      (PTHR1) regulates receptor signaling in vitro, but the role of this
      phosphorylation in vivo is uncertain. We investigated this role by injecting
      "knock-in" mice expressing a phosphorylation-deficient (PD) PTHR1 with PTH
      ligands and assessing acute biologic responses. Following injection with PTH (1
      34), or with a unique, long-acting PTH analog, PD mice, compared with WT mice,
      exhibited enhanced increases in cAMP levels in the blood, as well as enhanced
      cAMP production and gene expression responses in bone and kidney tissue.
      Surprisingly, however, the hallmark hypercalcemic and hypophosphatemic responses
      were markedly absent in the PD mice, such that paradoxical hypocalcemic and
      hyperphosphatemic responses were observed, quite strikingly with the long-acting
      PTH analog. Spot urine analyses revealed a marked defect in the capacity of the
      PD mice to excrete phosphate, as well as cAMP, into the urine in response to PTH
      injection. This defect in renal excretion was associated with a severe, PTH
      induced impairment in glomerular filtration, as assessed by the rate of FITC
      inulin clearance from the blood, which, in turn, was explainable by an overly
      exuberant systemic hypotensive response. The overall findings demonstrate the
      importance in vivo of PTH-induced phosphorylation of the PTHR1 in regulating
      acute ligand responses, and they serve to focus attention on mechanisms that
      underlie the acute calcemic response to PTH and factors, such as blood phosphate
      levels, that influence it.

PMID- 23533277
TI  - Development and in vivo efficacy of targeted polymeric inflammation-resolving
      nanoparticles.
AB  - Excessive inflammation and failed resolution of the inflammatory response are
      underlying components of numerous conditions such as arthritis, cardiovascular
      disease, and cancer. Hence, therapeutics that dampen inflammation and enhance
      resolution are of considerable interest. In this study, we demonstrate the
      proresolving activity of sub-100-nm nanoparticles (NPs) containing the anti
      inflammatory peptide Ac2-26, an annexin A1/lipocortin 1-mimetic peptide. These
      NPs were engineered using biodegradable diblock poly(lactic-co-glycolic acid)-b
      polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol
      collagen IV-targeted polymers. Using a self-limited zymosan-induced peritonitis
      model, we show that the Ac2-26 NPs (100 ng per mouse) were significantly more
      potent than Ac2-26 native peptide at limiting recruitment of polymononuclear
      neutrophils (56% vs. 30%) and at decreasing the resolution interval up to 4 h.
      Moreover, systemic administration of collagen IV targeted Ac2-26 NPs (in as low
      as 1 ug peptide per mouse) was shown to significantly block tissue damage in hind
      limb ischemia-reperfusion injury by up to 30% in comparison with controls.
      Together, these findings demonstrate that Ac2-26 NPs are proresolving in vivo and
      raise the prospect of their use in chronic inflammatory diseases such as
      atherosclerosis.

PMID- 23533280
TI  - Candidate tumor suppressor BTG3 maintains genomic stability by promoting Lys63
      linked ubiquitination and activation of the checkpoint kinase CHK1.
AB  - B-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG/
      Transducer of ErbB2 gene family and is induced by genotoxic stress in a p53- and
      Checkpoint kinase 1 (CHK1)-dependent manner. Down-regulation of BTG3 has been
      observed in human cancers, suggesting that it plays an important role in tumor
      suppression, although the underlying mechanisms are unclear. Here, we report that
      BTG3 interacts with CHK1, a key effector kinase in the cell cycle checkpoint
      response, and regulates its phosphorylation and activation. Upon interaction,
      BTG3 mediates K63-linked ubiquitination of CHK1 at Lys132 through the cullin-RING
      ligase 4(Cdt2) E3 complex, thus facilitating CHK1 chromatin association. We show
      that BTG3-depleted cells phenocopy those CHK1-deficient cells, exhibiting
      increased cell death after replication block and impaired chromosome alignment
      and segregation. These defects could be corrected by wild-type BTG3 but not by a
      mutant impaired in CHK1 interaction. We propose that BTG3-dependent CHK1
      ubiquitination contributes to its chromatin localization and activation and that
      a defect in this regulation may increase genome instability and promote
      tumorigenesis.

PMID- 23533281
TI  - Subarachnoid haemorrhage as the presenting feature of lumbar spinal arteriovenous
      malformation.

PMID- 23533283
TI  - Obsessive-compulsive behavior as presenting symptom of primary antiphospholipid
      syndrome.
AB  - OBJECTIVE: This study aimed to improve understanding and treatment of psychiatric
      symptoms in antiphospholipid syndrome (APS) and to present an approach to the
      medical management of patients presenting with obsessive-compulsive disorder
      (OCD) with suspected neurovascular pathology. METHOD: A 15-year-old boy presented
      with severe OCD of recent onset. An infarct of the caudate nucleus was identified
      as the initial presentation of primary APS. This case report includes a selective
      literature review of the neuropsychiatric correlates of APS. RESULTS: The patient
      had OCD for 3 months with increasing symptoms resulting in admission for
      psychiatric reasons. After referral to the emergency department 3 weeks later, an
      infarct of the caudate nucleus was documented using magnetic resonance images of
      the brain, and APS was diagnosed based on additional laboratory findings.
      Anticoagulant treatment (enoxaparin and phenprocoumon) in this patient was
      effective in reducing obsessive-compulsive symptom severity. CONCLUSION: OCD may
      present as a neuropsychiatric manifestation of APS. The present observations are
      consistent with a thrombotic mechanism for neurologic or psychiatric symptoms in
      APS. In general, routine medical workup for childhood OCD is not indicated, but a
      comprehensive psychiatric, medical, and family history taking and physical
      examination are essential, particularly if OCD is of recent onset. The role of
      anticoagulant therapy in neuropsychiatric manifestations of APS without the
      presence of a cerebral infarct requires further research.

PMID- 23533282
TI  - Low socioeconomic status and psychological distress as synergistic predictors of
      mortality from stroke and coronary heart disease.
AB  - BACKGROUND: The purpose of this study was to test whether lower socioeconomic
      status (SES) augments the effect of psychological distress on mortality from
      stroke or coronary heart disease (CHD). METHODS: We prospectively linked data
      from 66,500 participants 35 years or older in the Health Survey for England,
      selected using stratified random sampling from 1994 to 2004, and free of
      cardiovascular disease and cancer at baseline, with mortality records. The median
      follow-up time was 7.9 years. SES was indexed by occupational class, and
      psychological distress was assessed using the 12-item General Health
      Questionnaire (GHQ-12). RESULTS: After adjustment for demographic and clinical
      variables, both psychological distress and low SES were associated with increased
      mortality: the hazard ratios (HR) for one-category increase in low SES (three
      categories in total) were 1.15 for stroke-death (95% confidence interval [CI] =
      1.00-1.31, p = .043) and 1.24 for CHD-death (95% CI = 1.09-1.41, p = .001); the
      HR for one-category increase in GHQ-12 (three categories in total) was 1.18 for
      stroke-death (95% CI = 1.07-1.30, p = .001) and 1.24 for CHD-death (95% CI = 1.13
      1.36, p < .001). In stratified analyses, the strongest associations were found in
      the lowest SES categories: the HR for GHQ-12 toward stroke-death was 1.15 in high
      SES participants (95% CI = 0.97-1.37, p = .107) and 1.31 in low-SES ones (95% CI
      = 1.13-1.51, p < .001); the HR for GHQ-12 toward CHD-death was 1.10 in high-SES
      participants (95% CI = 0.97-1.25, p = .129) and 1.33 in low-SES ones (95% CI =
      1.19-1.48, p < .001). CONCLUSIONS: People in low socioeconomic circumstances are
      more vulnerable to the adverse effect of psychological distress. This pattern
      should be taken into account when evaluating the association between psychosocial
      variables and health outcomes.

PMID- 23533284
TI  - Depressive symptoms and all-cause mortality in a nationally representative
      longitudinal study with time-varying covariates.
AB  - OBJECTIVE: To examine the relationship between depressive symptoms and all-cause
      mortality in a longitudinal study with a nationally representative sample.
      Research has shown that depressive symptoms increase mortality risk, but results
      have been inconclusive regarding the role of physical health conditions in the
      relationship. This study asks whether the association between depressive symptoms
      and mortality exists independent of contemporaneous physical health conditions,
      is spurious because of prior physical health conditions, or is mediated by later
      physical health conditions. METHODS: Data are drawn from the Americans' Changing
      Lives Study, a sample of 3617 noninstitutionalized Americans aged 25 years or
      older. Respondents were interviewed in 1986, 1989, 1994, and 2002. Depressive
      symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]), physical
      health, and confounders were measured at each wave. Mortality status was
      ascertained yearly through 2007. Discrete time hazard models with time-varying
      covariates were used to estimate the association between CES-D scores and
      mortality. RESULTS: Between 1986 and 2007, 1411 survey respondents died.
      Depressive symptoms were associated with mortality after adjusting for stress,
      coping characteristics, social support, and health behaviors (odds ratio [OR] =
      1.23, 95% confidence interval [CI] = 1.11-1.36, p < .001). However, the
      association became nonsignificant after accounting for contemporaneous physical
      health conditions (OR = 1.06, 95% CI = 0.95-1.17, p = .31). Prior physical health
      conditions did not explain the association (OR = 1.24, 95% CI = 1.11-1.39, p <
      .001). The association between lagged depressive symptoms and mortality was
      mediated by later physical health conditions (p = .94). CONCLUSIONS: Study
      findings support the mediation hypothesis. The effect of depressive symptoms on
      mortality is mediated by later physical health.

PMID- 23533286
TI  - Cortical abnormalities in patients with migraine: a surface-based analysis.
AB  - PURPOSE: To explore the patterns of cortical thickness and cortical surface area
      abnormalities in patients with migraine (with the expectation of seeing reduced
      cortical thickness and surface area in regions subserving nociception and
      increased cortical thickness and surface area in regions involved in migraine
      pathogenesis) and to assess their correlation with clinical and radiologic
      manifestations of the disease. MATERIALS AND METHODS: Approval of the local
      ethical committee was obtained, as well as written informed consent from each
      participant. T2-weighted and three-dimensional T1-weighted magnetic resonance
      images of the brain were acquired in 63 migraineurs and 18 matched healthy
      control subjects. Cortical thickness and cortical surface area were estimated. By
      using a general linear model approach, a vertex-by-vertex statistical analysis (P
      < .01) was used to assess between-group comparisons (migraineurs vs control
      subjects, the aura effect, the effect of white matter hyperintensities [WMHs])
      and the correlations between cortical thickness and surface area measurements and
      patients' clinical and radiologic characteristics. RESULTS: Compared with control
      subjects, patients with migraine showed reduced cortical thickness and surface
      area in regions subserving pain processing (P < .01). These two metrics were
      increased in regions involved in executive functions and visual motion processing
      (P < .01). The anatomic overlap of cortical thickness and cortical surface area
      abnormalities was only minimal, with cortical surface area abnormalities being
      more pronounced and more widely distributed than cortical thickness
      abnormalities. Cortical thickness and surface area abnormalities were related to
      aura and WMHs (P < .01) but not to disease duration and attack frequency.
      CONCLUSION: Cortical abnormalities occur in migraineurs and may represent the
      results of a balance between an intrinsic predisposition, as suggested by
      cortical surface area abnormalities, and disease-related processes, as indicated
      by cortical thickness abnormalities.

PMID- 23533285
TI  - Socioeconomic status gradients in inflammation in adolescence.
AB  - OBJECTIVE: To determine whether lower socioeconomic status (SES), broadly
      defined, is associated with increased inflammation in adolescence and whether
      adiposity mediates these relationships. METHODS: Fasting blood samples from 941
      non-Hispanic black and white adolescents enrolled in a suburban, Midwestern
      school district were assayed for proinflammatory biomarkers (interleukin-6 [IL
      6], tumor necrosis factor alpha soluble receptor 2 fibrinogen). A parent reported
      objective SES (parent education [E1 <= high school, E2 = some college, E3 =
      college graduate, E4 = professional degree], household income), and youth
      perceived SES (PSES). Multivariable linear regressions assessed the relationship
      of SES measures to biomarkers adjusting for age, race, sex, and puberty status.
      In the final step, body mass index (BMI) z score (BMIz) was added to models, and
      Sobel tests were performed to assess mediation by adiposity. RESULTS: Parent
      education was inversely associated with IL-6 (betaE1 = .11, betaE2 = .10, betaE3
      = .02; p < .001). This association was attenuated but remained significant after
      BMIz adjustment (p = .01). Sobel testing confirmed BMIz's partial mediating role
      (p < .001). Parent education was also inversely associated with sTNFR2 (betaE1 =
      .03, betaE2 = .02, betaE3 = .001; p = .01); this relationship was mediated by
      BMIz. Although no main effect was noted for PSES, PSES by race interactions was
      observed for sTNFR2 (p = .02) and IL-6 (p = .06). High PSES was associated with
      lower sTNFR2 and IL-6 for white but not black youth. There were no associations
      with household income. CONCLUSIONS: Social disadvantage, specifically low parent
      education, is associated with increased inflammation in adolescence. Adiposity
      explains some but not all associations, suggesting that other mechanisms link
      lower SES to inflammation. High PSES is associated with lower inflammation for
      white but not black youth.

PMID- 23533287
TI  - Multiple sclerosis: white and gray matter damage associated with balance deficit
      detected at static posturography.
AB  - PURPOSE: To combine two unbiased (ie, without any a priori hypothesis) magnetic
      resonance (MR) imaging processing approaches, tract-based spatial statistics and
      voxel-based morphometry, to investigate the relationship between white matter and
      gray matter damage and computer-based measures of balance impairment assessed at
      static posturography in patients with multiple sclerosis (MS). MATERIALS AND
      METHODS: Institutional review board approval and written informed consent were
      obtained. Forty-five ambulatory patients with MS (34 women, 11 men) and 25 sex-
      and age-matched healthy control subjects were assessed by using a force platform
      to compute the displacement (in millimeters) of the body center of pressure in 30
      seconds. In a separate session, patients underwent MR imaging at 3 T, including a
      dual-echo fast spin-echo sequence, a T1-weighted volume sequence, and a diffusion
      tensor imaging sequence. T2 lesion volumes were assessed by using a semiautomated
      technique. Tract-based spatial statistics and voxel-based morphometry were used
      for the white and gray matter analyses, respectively, to correlate force platform
      measures with diffusion-tensor imaging parameters and regional gray matter
      volumes, adjusting for the patients' sex, age, disease duration, and lesion
      volume. RESULTS: Patients with MS had worse postural stability, widespread
      alterations in most white matter bundles, and gray matter atrophy in several
      brain regions compared with control subjects. In patients with MS, balance
      impairment was correlated with worse diffusion-tensor imaging parameters along
      the cerebellar connections and supratentorial associative white matter bundles (P
      < .05, threshold-free cluster enhancement corrected). Gray matter atrophy of the
      superior lobules of the cerebellum (IV, V, VI), and lobules VIII also correlated
      with worse posturometric values (P < .05, family-wise error corrected).
      CONCLUSION: Imbalance due to MS appears to be related to the disconnection
      between the spinal cord, cerebellum, and cerebral cortex, which in turn produces
      atrophy of the sensory motor cerebellar regions that are functionally connected
      with specific cortical areas.

PMID- 23533288
TI  - High sensitivity of diffusion-weighted MR imaging for the detection of liver
      metastases from neuroendocrine tumors: comparison with T2-weighted and dynamic
      gadolinium-enhanced MR imaging.
AB  - PURPOSE: To compare the sensitivity and specificity of diffusion-weighted (DW)
      magnetic resonance (MR) imaging for identifying liver metastases from
      neuroendocrine tumor (NET) to those of T2-weighted fast spin-echo (FSE) and three
      dimensional dynamic gadolinium-enhanced MR imaging, with surgical and
      histopathologic findings as the reference standard. MATERIALS AND METHODS: This
      retrospective study was approved by institutional review board, and informed
      consent was waived. Fifty-nine patients with NETs (41 patients with 162 liver
      metastases, and 18 control subjects with no liver metastases) underwent MR
      imaging that included DW, T2-weighted FSE, and dynamic gadolinium-enhanced MR
      sequences. Images were retrospectively reviewed by two abdominal radiologists,
      independently, for the detection and characterization of liver metastases. MR
      findings were compared with histopathologic and intraoperative ultrasonography
      findings for metastasis on a lesion-by-lesion basis to determine the sensitivity
      of each MR sequence alone and combined. Specificity was calculated by using the
      control population. Interreader agreement for each MR sequence and McNemar test
      were also calculated. RESULTS: There was excellent agreement between observers 1
      and 2 for characterizing liver metastases at per-lesion analysis (kappa
      coefficient: 0.86-1.00). DW MR was more sensitive (observer 1: sensitivity, 71.6%
      [116 of 162], 95% confidence interval [CI]: 64.2%, 78.0%; observer 2:
      sensitivity, 71.0% [115 of 162], 95% CI: 63.6%, 77.4%) than T2-weighted FSE
      (observer 1: sensitivity, 55.6% [90 of 162], 95% CI: 47.9%, 63.0%; observer 2:
      sensitivity, 55.6% [90 of 162], 95% CI: 47.9%, 63.0%) and dynamic gadolinium
      enhanced MR (observer 1: sensitivity, 47.5% [77 of 162], 95% CI: 34.0%, 55.2%;
      observer 2: sensitivity, 48.1% [78 of 162], 95% CI: 40.6%, 55.8%) (P < .001 for
      both, McNemar test). The specificity of these sequences ranged from 88.9% to 100%
      (DW MR vs T2-weighted FSE MR: P > .99, DW MR vs dynamic gadolinium-enhanced MR: P
      = .61, and T2-weighted FSE MR vs dynamic gadolinium-enhanced MR: P = .61, McNemar
      test). CONCLUSION: DW MR imaging was more sensitive for the detection and
      characterization of liver metastases from NETs than T2-weighted FSE and dynamic
      gadolinium-enhanced MR imaging and should be systematically performed.

PMID- 23533289
TI  - Knee derangements: comparison of isotropic 3D fast spin-echo, isotropic 3D
      balanced fast field-echo, and conventional 2D fast spin-echo MR imaging.
AB  - PURPOSE: To compare diagnostic performance, subjective image quality, and
      artifacts of isotropic three-dimensional (3D) intermediate-weighted (IW) fast
      spin-echo (SE), isotropic 3D balanced fast field-echo (FFE), and conventional two
      dimensional (2D) fast SE 3.0-T MR sequences in evaluation of cartilage,
      ligaments, menisci, and osseous knee structures in symptomatic patients.
      MATERIALS AND METHODS: Institutional review board approval and waiver of informed
      consent were obtained for this HIPAA-compliant study. One hundred MR studies,
      each with three data sets (3D IW fast SE, 3D balanced FFE, 2D fast SE), were
      reviewed retrospectively. Two radiologists independently evaluated images for
      cartilaginous defects, anterior cruciate ligament (ACL), posterior cruciate
      ligament (PCL), medial meniscus (MM), lateral meniscus (LM) tears, subchondral
      bone marrow signal abnormalities, subjective image quality, and image artifacts.
      Arthroscopic results were the reference standard. Statistical analysis was
      performed to calculate interobserver agreement and compare diagnostic performance
      of sequences. RESULTS: Sensitivity and specificity were greater than 85% for all
      lesions. For cartilaginous defects, sensitivity of 3D IW fast SE was
      significantly greater than that of 3D balanced FFE (95.5% vs 89.7%). Sensitivity
      of 3D IW fast SE and 2D fast SE for MM, LM, and ACL tears tended to be greater
      than that of 3D balanced FFE. IW fast SE had a higher detection rate for
      subchondral bone marrow signal abnormality than did 3D balanced FFE (34% vs 21%);
      it also had the best image quality and fewest artifacts, followed by 2D fast SE
      and 3D balanced FFE. Interobserver agreement was excellent for evaluation of all
      intraarticular structures (kappa = 0.85-1) and good to excellent for detection of
      subchondral bone marrow signal abnormality (kappa = 0.76-0.91). CONCLUSION: The
      performance of IW fast SE is superior to that of balanced FFE in evaluation of
      cartilaginous defects, with no significant difference in performance between 2D
      fast SE, 3D IW fast SE, and 3D balanced FFE in evaluation of meniscal and
      ligament tears. Subchondral bone marrow signal abnormality is more easily seen on
      3D IW fast SE images, with better subjective image quality and fewer artifacts,
      than on images obtained with other techniques.

PMID- 23533290
TI  - Evaluation of retained testes in adolescent girls and women with complete
      androgen insensitivity syndrome.
AB  - PURPOSE: To evaluate the magnetic resonance (MR) imaging appearance of the testes
      in women with complete androgen insensitivity syndrome (CAIS), including any
      benign or malignant changes. MATERIALS AND METHODS: This was a retrospective
      review of the testicular MR images and histologic reports from 25 patients with
      CAIS who chose to retain their testes beyond age 16 years and who were imaged
      between January 2004 and December 2010. Ethical approval was obtained, and
      informed consent was obtained from each subject to review the medical records,
      images, and histologic slides and reports. Imaging and histologic findings were
      compared. RESULTS: Twelve patients (mean age, 24 years; age range, 18-39 years)
      retained their testes and 13 (mean age, 22 years; age range, 17-37 years)
      eventually underwent gonadectomy. Review of the MR images showed that testicular
      parenchyma was heterogeneous in 30 of 46 testes (65%). The most common changes on
      MR images included simple-looking paratesticular cysts (34 of 46 testes, 74%) and
      low-signal-intensity, well-defined Sertoli cell adenomas (26 of 46 testes, 56%).
      Correlation of the histologic and MR imaging findings showed that MR imaging
      could correctly depict the presence or absence of Sertoli cell adenomas in 19 of
      23 testes (83%). Paratesticular cysts were correctly detected in 22 of 23 testes
      (96%). Microscopic examination showed that the testes were composed of atrophic
      seminiferous tubules, whereas germ cells were found in 13 of 26 testes (50%). All
      paratesticular cysts were confirmed to be benign; however, a focus of
      intratubular germ cell neoplasia was found in a Sertoli cell adenoma.
      Premalignant foci were detected in three patients, two with intratubular germ
      cell neoplasia and one with sex cord tumor with annular tubules. No invasive
      cancers were found. CONCLUSION: MR imaging is accurate in the detection of
      testicular changes, including paratesticular cysts and Sertoli cell adenomas.
      Although these changes are usually benign, Sertoli adenomas can sometimes harbor
      premalignant lesions. MR imaging cannot depict premalignant changes; therefore,
      the standard of care for patients with CAIS should remain gonadectomy after
      puberty.

PMID- 23533292
TI  - Mathematical modelling in developmental biology.
AB  - In recent decades, molecular and cellular biology has benefited from numerous
      fascinating developments in experimental technique, generating an overwhelming
      amount of data on various biological objects and processes. This, in turn, has
      led biologists to look for appropriate tools to facilitate systematic analysis of
      data. Thus, the need for mathematical techniques, which can be used to aid the
      classification and understanding of this ever-growing body of experimental data,
      is more profound now than ever before. Mathematical modelling is becoming
      increasingly integrated into biological studies in general and into developmental
      biology particularly. This review outlines some achievements of mathematics as
      applied to developmental biology and demonstrates the mathematical formulation of
      basic principles driving morphogenesis. We begin by describing a mathematical
      formalism used to analyse the formation and scaling of morphogen gradients. Then
      we address a problem of interplay between the dynamics of morphogen gradients and
      movement of cells, referring to mathematical models of gastrulation in the chick
      embryo. In the last section, we give an overview of various mathematical models
      used in the study of the developmental cycle of Dictyostelium discoideum, which
      is probably the best example of successful mathematical modelling in
      developmental biology.

PMID- 23533291
TI  - Influence of energy balance on the antimicrobial peptides S100A8 and S100A9 in
      the endometrium of the post-partum dairy cow.
AB  - Uterine inflammation occurs after calving in association with extensive
      endometrial remodelling and bacterial contamination. If the inflammation
      persists, it leads to reduced fertility. Chronic endometritis is highly prevalent
      in high-yielding cows that experience negative energy balance (NEB) in early
      lactation. This study investigated the effect of NEB on the antimicrobial
      peptides S100A8 and S100A9 in involuting uteri collected 2 weeks post partum.
      Holstein-Friesian cows (six per treatment) were randomly allocated to two
      interventions designed to produce mild or severe NEB (MNEB and SNEB) status.
      Endometrial samples were examined histologically, and the presence of
      neutrophils, macrophages, lymphocytes and natural killer cells was confirmed
      using haematoxylin and eosin and immunostaining. SNEB cows had greater signs of
      uterine inflammation. Samples of previously gravid uterine horn were used to
      localise S100A8 and S100A9 by immunohistochemistry. Both S100 proteins were
      present in bovine endometrium with strong staining in epithelial and stromal
      cells and in infiltrated leucocytes. Immunostaining was significantly higher in
      SNEB cows along with increased numbers of segmented neutrophils. These results
      suggest that the metabolic changes of a post-partum cow suffering from NEB delay
      uterine involution and promote a chronic state of inflammation. We show that
      upregulation of S100A8 and S100A9 is clearly a key component of the early
      endometrial response to uterine infection. Further studies are warranted to link
      the extent of this response after calving to the likelihood of cows developing
      endometritis and to their subsequent fertility.

PMID- 23533293
TI  - Outcome of nicotine replacement therapy in patients admitted to ICU: a randomized
      controlled double-blind prospective pilot study.
AB  - BACKGROUND: The effect of nicotine withdrawal in smokers admitted to the ICU is
      not well understood, so the role of nicotine replacement therapy (NRT) in those
      patients is controversial. OBJECTIVE: To determine whether NRT in ICU patients
      affects the need for sedatives/analgesics, ventilator days, and ICU stay.
      METHODS: In a 20-bed ICU, 40 subjects were randomized to either a 21 mg nicotine
      patch or a placebo nicotine patch daily until either ICU discharge, transfer to a
      medical floor, or 10 weeks in the ICU. We collected data on sedatives/analgesics
      use during ICU stay and use and duration of mechanical ventilation . RESULTS:
      There were 27 male and 13 female subjects. The mean age was 57.4 y in the
      intervention group and 52.5 y in the control group. The mean Acute Physiology and
      Chronic Health Evaluation II score was 14.3 in the intervention group and 13.8 in
      the control group. The mean ICU stay was 4.5 d in the intervention group and 7 d
      in the control group. The mean number of days on ventilator was 1.9 in the
      intervention group and 3.5 in the control group. The number of days on
      sedation/analgesia was less in the intervention group than in the control group.
      CONCLUSIONS: Although ICU stay and ventilator days decreased numerically in this
      pilot study, statistically there was no beneficial effect from NRT.
      (International Standard Randomised Controlled Trial Register ISRCTN66928309).

PMID- 23533294
TI  - Laboratory test of a visual sputum suctioning system.
AB  - BACKGROUND: Conventional sputum suctioning is a routine clinical practice, but
      complications may arise from the blind manipulation of the catheter. Recently, a
      visual sputum suctioning system (VSSS) was developed, and we tested this new
      system in a laboratory setting. METHODS: We used coagulant concentrations of 1.5%
      and 3.0% to simulate mucus and sputum. Conventional single-lumen and triple-lumen
      catheters were inserted separately into a beaker for sputum suctioning (15 s, 200
      mm Hg). A micro-imaging fiber was integrated into the triple-lumen catheter to
      create the VSSS. The single-lumen catheter and the VSSS were inserted separately
      into the mouth cavity, the nasal cavity, the tracheostomy tube, and the
      endotracheal tube of a human analog model for further comparisons. RESULTS: As
      the suction channel of the triple-lumen catheter was reduced by 46.8%, the amount
      of simulant it suctioned was significantly less than that suctioned by the single
      lumen catheter. However, under real-time guidance, the VSSS suctioned more
      simulant than the conventional single-lumen catheter in the human analog model.
      CONCLUSION: Sputum suctioning with the VSSS was feasible. Because of its real
      time imaging guidance, the efficiency of the VSSS procedure was greater than that
      of the conventional single-lumen catheter. Therefore, this system may provide a
      new platform for sputum suctioning.

PMID- 23533295
TI  - Oxygen injection site affects FIO2 during noninvasive ventilation.
AB  - BACKGROUND: Most portable bi-level positive airway pressure devices are not
      equipped with air-oxygen blenders for precisely regulating oxygen concentrations,
      and supplemental oxygen must be added to increase the F(IO2). Very few studies
      have investigated the factors that affect F(IO2), and their conclusions have been
      inconsistent. We investigated in vitro noninvasive ventilation (NIV) parameters
      and their effects on F(IO2), particularly the effect of the oxygen injection
      site. METHODS: NIV was simulated with a test lung and manikin setup. F(IO2) was
      measured with 4 oxygen injection sites (mask, in front of the exhalation valve,
      at the humidifier outlet, and proximal to the ventilator), with 3 exhalation
      valve types, with 2 oxygen flows, and with 4 combinations of inspiratory and
      expiratory pressure. RESULTS: Oxygen flow, inspiratory and expiratory pressure,
      and exhalation valve type all affected F(IO2). For a given oxygen flow, the
      oxygen injection site was the most important factor that affected F(IO2). The
      oxygen injection site that was closest to the patient (on the mask) had the
      higher F(IO2) (P < .001). CONCLUSIONS: The oxygen injection site had the greatest
      effect on F(IO2) during NIV.

PMID- 23533296
TI  - Indian Journal of Orthopaedics: Journey continues.

PMID- 23533297
TI  - Tourniquets in orthopedic surgery.

PMID- 23533298
TI  - Author's reply.

PMID- 23533300
TI  - Anti-inflammatory effects of ellagic acid on acute lung injury induced by acid in
      mice.
AB  - Acute lung injury (ALI) is characterized by alveolar edema and uncontrolled
      neutrophil migration to the lung, and no specific therapy is still available.
      Ellagic acid, a compound present in several fruits and medicinal plants, has
      shown anti-inflammatory activity in several experimental disease models. We used
      the nonlethal acid aspiration model of ALI in mice to determine whether
      preventive or therapeutic administration of ellagic acid (10 mg/kg; oral route)
      could interfere with the development or establishment of ALI inflammation.
      Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control. In
      both preventive and therapeutic treatments, ellagic acid reduced the vascular
      permeability changes and neutrophil recruitment to the bronchoalveolar lavage
      fluid (BALF) and to lung compared to the vehicle. In addition, the ellagic acid
      accelerated the resolution for lung neutrophilia. Moreover, ellagic acid reduced
      the COX-2-induced exacerbation of inflammation. These results were similar to the
      dexamethasone. However, while the anti-inflammatory effects of dexamethasone
      treatment were due to the reduced activation of NF- kappa B and AP-1, the ellagic
      acid treatment led to reduced BALF levels of IL-6 and increased levels of IL-10.
      In addition, dexamethasone treatment reduced IL-1 beta. Together, these findings
      identify ellagic acid as a potential therapeutic agent for ALI-associated
      inflammation.

PMID- 23533299
TI  - Mitochondrial dysfunction: a basic mechanism in inflammation-related non
      communicable diseases and therapeutic opportunities.
AB  - Obesity is not necessarily a predisposing factor for disease. It is the handling
      of fat and/or excessive energy intake that encompasses the linkage of
      inflammation, oxidation, and metabolism to the deleterious effects associated
      with the continuous excess of food ingestion. The roles of cytokines and insulin
      resistance in excessive energy intake have been studied extensively. Tobacco use
      and obesity accompanied by an unhealthy diet and physical inactivity are the main
      factors that underlie noncommunicable diseases. The implication is that the
      management of energy or food intake, which is the main role of mitochondria, is
      involved in the most common diseases. In this study, we highlight the importance
      of mitochondrial dysfunction in the mutual relationships between causative
      conditions. Mitochondria are highly dynamic organelles that fuse and divide in
      response to environmental stimuli, developmental status, and energy requirements.
      These organelles act to supply the cell with ATP and to synthesise key molecules
      in the processes of inflammation, oxidation, and metabolism. Therefore, energy
      sensors and management effectors are determinants in the course and development
      of diseases. Regulating mitochondrial function may require a multifaceted
      approach that includes drugs and plant-derived phenolic compounds with
      antioxidant and anti-inflammatory activities that improve mitochondrial
      biogenesis and act to modulate the AMPK/mTOR pathway.

PMID- 23533301
TI  - The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with
      type 1 diabetes.
AB  - IL-6 is a pleiotropic cytokine involved in the regulation of the immune response,
      inflammation, and hematopoeisis. Its elevated levels are found in a range of
      autoimmune and chronic inflammatory diseases. IL-6 is also involved in regulation
      of the balance between two T cell subsets: Tregs and Th17, which have
      contradictory functions in the control of inflammation. The present study
      provides a quantitative analysis regarding the Th17/Treg cell balance in
      peripheral blood of children with type 1 diabetes and its association with serum
      IL-6 level.

PMID- 23533302
TI  - Aged garlic extract improves adiponectin levels in subjects with metabolic
      syndrome: a double-blind, placebo-controlled, randomized, crossover study.
AB  - BACKGROUND: Garlic (Allium sativum) has been shown to have important benefits in
      individuals at high cardiovascular risk. The aim of the present study was to
      evaluate the effects of the administration of aged garlic extract (AGE) on the
      risk factors that constitute the cluster of metabolic syndrome (MS). METHODS AND
      DESIGN: Double-blind, crossover, randomized, placebo-controlled clinical trial to
      assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12
      weeks of AGE and 12 weeks of placebo), on subjects with MS. RESULTS: The
      administration of AGE increased the plasma levels of adiponectin (P = 0.027). No
      serious side effects associated with the intervention were reported. CONCLUSION:
      The present results have shown for the first time that the administration of AGE
      for 12 weeks increased plasma adiponectin levels in patients with MS. This
      suggests that AGE might be a useful, novel, nonpharmacological therapeutic
      intervention to increase adiponectin and to prevent cardiovascular (CV)
      complications in individuals with MS.

PMID- 23533303
TI  - Pharmacological inhibition of p38 mitogen-activated protein kinases affects
      KC/CXCL1-induced intraluminal crawling, transendothelial migration, and
      chemotaxis of neutrophils in vivo.
AB  - p38 mitogen-activated protein kinase (MAPK) signalling is critical in the
      pathophysiology of a variety of inflammatory processes. Leukocyte recruitment to
      the site of inflammation is a multistep process governed by specific signalling
      cascades. After adhesion in the lumen, many leukocytes crawl to optimal sites at
      endothelial junctions and transmigrate to extravascular tissue in a Mac-1
      dependent manner. The signalling mechanisms that regulate postadhesion steps of
      intraluminal crawling, transmigration, and chemotaxis in tissue remain
      incompletely understood. The present study explored the effect of p38 MAPK
      inhibitor SB203580 on various parameters of neutrophil recruitment triggered by
      chemokine KC (CXCL1) gradient. Neutrophil-endothelial interactions in
      microvasculature of murine cremaster muscle were determined using intravital
      microscopy and time-lapsed video analysis. SB203580 (100 nM) did not change
      leukocyte rolling but significantly attenuated neutrophil adhesion, emigration,
      and transmigration and impaired the initiation of neutrophil crawling and
      transmigration. In response to KC chemotactic gradient, SB203580 significantly
      reduced the velocity of migration and chemotaxis index of neutrophils in tissue.
      The upregulation of Mac-1 expression in neutrophils stimulated by KC was
      significantly blunted by SB203580 in vitro. Collectively, our findings
      demonstrate that pharmacological suppression of p38 MAPK significantly impairs
      multiple steps of neutrophil recruitment in vivo.

PMID- 23533304
TI  - Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain
      relief and neuroprotection share a PPAR-alpha-mediated mechanism.
AB  - Neuropathic syndromes which are evoked by lesions to the peripheral or central
      nervous system are extremely difficult to treat, and available drugs rarely joint
      an antihyperalgesic with a neurorestorative effect. N-Palmitoylethanolamine (PEA)
      exerts antinociceptive effects in several animal models and inhibits peripheral
      inflammation in rodents. Aimed to evaluate the antineuropathic properties of PEA,
      a damage of the sciatic nerve was induced in mice by chronic constriction injury
      (CCI) and a subcutaneous daily treatment with 30 mg kg(-1) PEA was performed. On
      the day 14, PEA prevented pain threshold alterations. Histological studies
      highlighted that CCI induced oedema and an important infiltrate of CD86 positive
      cells in the sciatic nerve. Moreover, osmicated preparations revealed a decrease
      in axon diameter and myelin thickness. Repeated treatments with PEA reduced the
      presence of oedema and macrophage infiltrate, and a significant higher myelin
      sheath, axonal diameter, and a number of fibers were observable. In PPAR- alpha
      null mice PEA treatment failed to induce pain relief as well as to rescue the
      peripheral nerve from inflammation and structural derangement. These results
      strongly suggest that PEA, via a PPAR- alpha -mediated mechanism, can directly
      intervene in the nervous tissue alterations responsible for pain, starting to
      prevent macrophage infiltration.

PMID- 23533305
TI  - Eosinophil-derived neurotoxin is elevated in patients with amyotrophic lateral
      sclerosis.
AB  - BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive
      neurodegenerative disease characterized by loss of motor neurons in the
      brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation
      have been implicated in the pathophysiology of ALS. Members of the family of
      damage-associated molecular patterns, including reactive oxygen species, high
      mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in
      pathological conditions. In this study, we aim to discover new biomarker for
      detecting ALS. MATERIALS AND METHODS: We examined 44 patients with ALS, 41
      patients with Alzheimer's disease, 41 patients with Parkinson's disease, and 44
      healthy controls. The concentration of serum EDN was measured using an enzyme
      linked immunosorbent assay. RESULTS: EDN levels were significantly increased 2.17
      fold in the serum of patients with ALS as compared with healthy controls (P <
      0.05). No correlation between the levels of serum EDN and various clinical
      parameters of ALS was found. Moreover, the levels of serum EDN in patients with
      Parkinson's disease and Alzheimer's disease and healthy controls were similar.
      CONCLUSION: A higher level of serum EDN was found specifically in patients with
      ALS, indicating that EDN may participate in the pathophysiology of ALS.

PMID- 23533306
TI  - Cytokine levels in the serum of healthy subjects.
AB  - Growing knowledge about the cytokine network response has led to a better
      comprehension of mechanisms of pathologies and to the development of new
      treatments with biological drugs, able to block specific molecules of the immune
      response. Indeed, when the cytokine production is deregulated, diseases often
      occur. The understanding of the physiological mechanism of the cytokine network
      would be useful to better comprehend pathological conditions. Moreover, since the
      immune system and response change their properties with development, differences
      in patients' age should be taken into account, both in physiological and in
      pathological conditions. In this study, we analyzed the profile of 48 cytokines
      and chemokines in the serum of healthy subjects, comparing adults (>=18 years)
      with young children and children (1-6 and 7-17 years). We found that a certain
      number of cytokines were not being produced in healthy subjects; others showed a
      constant serum level amongst the groups. Certain cytokines exhibited a downward
      or an upward trend with increasing age. The remaining cytokines were up- or
      downregulated in the group of the children with respect to the other groups. In
      conclusion, we drew some kinds of guidelines about the physiological production
      of cytokines and chemokines, underling the difference caused by aging.

PMID- 23533307
TI  - Dual effect of serum amyloid A on the invasiveness of glioma cells.
AB  - Evidence sustains a role for the acute-phase protein serum amyloid A (SAA) in
      carcinogenesis and metastasis, and the protein has been suggested as a marker for
      tumor progression. Nevertheless, the demonstration of a direct activity of SAA on
      tumor cells is still incipient. We have investigated the effect of human
      recombinant SAA (rSAA) on two human glioma cell lines, A172 and T98G. rSAA
      stimulated the [(3)H]-thymidine incorporation of both lines, but had dual effects
      on migration and invasiveness which varied according to the cell line. In T98G,
      the rSAA increased migration and invasion behaviors whereas in A172 it decreased
      these behaviors. These findings agree with the effect triggered by rSAA on matrix
      metalloproteinases (MMPs) activities measured in a gelatinolytic assay. rSAA
      inhibited activity of both MMPs in A172 cells while increasing them in T98G
      cells. rSAA also affected the production of compounds present in the tumor
      microenvironment that orchestrate tumor progression, such as IL-8, the production
      of reactive oxygen species (ROS) and nitric oxide (NO). We also observed that
      both lines expressed all three of the isoforms of SAA: SAA1, SAA2, and SAA4.
      These data suggest that some tumor cells are responsive to SAA and, in these
      cases, SAA may have a role in cancer progression that varies according to the
      cell type.

PMID- 23533308
TI  - Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation
      after ischemic stroke.
AB  - Several studies have provided evidence with regard to the neuroprotection
      benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also
      promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This
      study investigates the influence of HBO therapy on the migration of BMSCs,
      neurogenesis, gliosis, and inflammation after stroke. Rats that sustained
      transient middle cerebral artery occlusion (MCAO) were treated with HBO three
      weeks or two days. The results were examined using a behavior test (modified
      neurological severity score, mNSS) and immunostaining to evaluate the effects of
      HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of
      neurotrophic factors was also evaluated. There was a lower mNSS score in the
      three-week HBO group when compared with the two-day HBO group. Mobilization of
      BMSCs to an ischemic area was more improved in long course HBO treatments,
      suggesting the duration of therapy is crucial for promoting the homing of BMSCs
      to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic
      factors and improve neurogenesis and gliosis. These effects may help in neuronal
      repair after ischemic stroke, and increasing the course of HBO therapy might
      enhance therapeutic effects on ischemic stroke.

PMID- 23533309
TI  - Characterization of macrophage phenotypes in three murine models of house-dust
      mite-induced asthma.
AB  - In asthma, an important role for innate immunity is increasingly being
      recognized. Key innate immune cells in the lungs are macrophages. Depending on
      the signals they receive, macrophages can at least have an M1, M2, or M2-like
      phenotype. It is unknown how these macrophage phenotypes behave with regard to
      (the severity of) asthma. We have quantified the phenotypes in three models of
      house dust mite (HDM-)induced asthma (14, 21, and 24 days). M1, M2, and M2-like
      phenotypes were identified by interferon regulatory factor 5 (IRF5), YM1, and IL
      10, respectively. We found higher percentages of eosinophils in HDM-exposed mice
      compared to control but no differences between HDM models. T cell numbers were
      higher after HDM exposure and were the highest in the 24-day HDM protocol. Higher
      numbers of M2 macrophages after HDM correlated with higher eosinophil numbers. In
      mice with less severe asthma, M1 macrophage numbers were higher and correlated
      negatively with M2 macrophages numbers. Lower numbers of M2-like macrophages were
      found after HDM exposure and these correlated negatively with M2 macrophages. The
      balance between macrophage phenotypes changes as the severity of allergic airway
      inflammation increases. Influencing this imbalanced relationship could be a novel
      approach to treat asthma.

PMID- 23533310
TI  - Regulatory role of GSK-3 beta on NF- kappa B, nitric oxide, and TNF- alpha in
      group A streptococcal infection.
AB  - Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize
      the associated morbidity and mortality represent a critical issue. Glycogen
      synthase kinase-3 beta (GSK-3 beta) is known to regulate inflammatory response in
      infectious diseases. However, the regulation of GSK-3 beta in GAS infection is
      still unknown. The present study investigates the interaction between GSK-3 beta
      , NF- kappa B, and possible related inflammatory mediators in vitro and in a
      mouse model. The results revealed that GAS could activate NF- kappa B, followed
      by an increased expression of inducible nitric oxide synthase (iNOS) and NO
      production in a murine macrophage cell line. Activation of GSK-3 beta occurred
      after GAS infection, and inhibition of GSK-3 beta reduced iNOS expression and NO
      production. Furthermore, GSK-3 beta inhibitors reduced NF- kappa B activation and
      subsequent TNF- alpha production, which indicates that GSK-3 beta acts upstream
      of NF- kappa B in GAS-infected macrophages. Similar to the in vitro findings,
      administration of GSK-3 beta inhibitor in an air pouch GAS infection mouse model
      significantly reduced the level of serum TNF- alpha and improved the survival
      rate. The inhibition of GSK-3 beta to moderate the inflammatory effect might be
      an alternative therapeutic strategy against GAS infection.

PMID- 23533312
TI  - Radical scavenging activity-based and AP-1-targeted anti-inflammatory effects of
      lutein in macrophage-like and skin keratinocytic cells.
AB  - Lutein is a naturally occurring carotenoid with antioxidative, antitumorigenic,
      antiangiogenic, photoprotective, hepatoprotective, and neuroprotective
      properties. Although the anti-inflammatory effects of lutein have previously been
      described, the mechanism of its anti-inflammatory action has not been fully
      elucidated. Therefore, in the present study, we aimed to investigate the
      regulatory activity of lutein in the inflammatory responses of skin-derived
      keratinocytes or macrophages and to elucidate the mechanism of its inhibitory
      action. Lutein significantly reduced several skin inflammatory responses,
      including increased expression of interleukin-(IL-) 6 from LPS-treated
      macrophages, upregulation of cyclooxygenase-(COX-) 2 from interferon- gamma
      /tumor necrosis-factor-(TNF-) alpha -treated HaCaT cells, and the enhancement of
      matrix-metallopeptidase-(MMP-) 9 level in UV-irradiated keratinocytes. By
      evaluating the intracellular signaling pathway and the nuclear transcription
      factor levels, we determined that lutein inhibited the activation of redox
      sensitive AP-1 pathway by suppressing the activation of p38 and c-Jun-N-terminal
      kinase (JNK). Evaluation of the radical and ROS scavenging activities further
      revealed that lutein was able to act as a strong anti-oxidant. Taken together,
      our findings strongly suggest that lutein-mediated AP-1 suppression and anti
      inflammatory activity are the result of its strong antioxidative and p38/JNK
      inhibitory activities. These findings can be applied for the preparation of anti
      inflammatory and cosmetic remedies for inflammatory diseases of the skin.

PMID- 23533313
TI  - Role of macrophages in the pathogenesis of atopic dermatitis.
AB  - Atopic dermatitis (AD) is one of the most common and most intensively studied
      chronic inflammatory skin diseases. Several cofactors, such as an impaired skin
      barrier function, modifications of the immune system, and a complex genetic
      background, direct the course of AD. Within this complex network, macrophages
      play a pivotal role in enhanced susceptibility to cutaneous infections and act as
      central connecting components in the pathogenesis of AD on the cellular level. In
      AD, macrophages are known to accumulate in acutely and chronically inflamed skin.
      During the early and short inflammatory phase, macrophages exert proinflammatory
      functions like antigen-presenting phagocytosis and the production of inflammatory
      cytokines and growth factors that facilitate the resolution of inflammation.
      However, persistence of pro-inflammatory activity and altered function of
      macrophages result in the development of chronic inflammatory diseases such as
      AD. The exact mechanism of macrophages activation in these processes is not yet
      completely understood. Further studies should be performed to clarify the
      dysregulated mechanism of macrophages activation in AD, and this would allow us
      to target these cells with versatile functions for therapeutic purpose and
      improve and control the disease. In this paper, we highlight the new findings on
      dysregulated function of macrophages and the importance of these cells in the
      pathogenesis of AD in general and the contribution of these cells in enhanced
      susceptibility against microbial infections in particular.

PMID- 23533311
TI  - Macrophage heterogeneity in respiratory diseases.
AB  - Macrophages are among the most abundant cells in the respiratory tract, and they
      can have strikingly different phenotypes within this environment. Our knowledge
      of the different phenotypes and their functions in the lung is sketchy at best,
      but they appear to be linked to the protection of gas exchange against microbial
      threats and excessive tissue responses. Phenotypical changes of macrophages
      within the lung are found in many respiratory diseases including asthma, chronic
      obstructive pulmonary disease (COPD), and pulmonary fibrosis. This paper will
      give an overview of what macrophage phenotypes have been described, what their
      known functions are, what is known about their presence in the different
      obstructive and restrictive respiratory diseases (asthma, COPD, pulmonary
      fibrosis), and how they are thought to contribute to the etiology and resolution
      of these diseases.

PMID- 23533314
TI  - Serum IL-12 is increased in Mexican obese subjects and associated with low-grade
      inflammation and obesity-related parameters.
AB  - Interleukin-(IL-) 12 has been recently suggested to participate during
      development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels
      have not been accurately determined in overweight and obese humans. We thus
      studied serum concentrations of IL-12 in Mexican adult individuals, examining
      their relationship with low-grade inflammation and obesity-related parameters. A
      total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese
      subjects participated in the study. Circulating levels of IL-12, tumor necrosis
      factor-alpha (TNF- alpha ), leptin, insulin, glucose, total cholesterol, and
      triglyceride were measured after overnight fasting in all of the study subjects.
      Waist circumference and body fat percentage were recorded for all the
      participants. Serum IL-12 was significantly higher in overweight and obese
      individuals than in normal weight controls. Besides being strongly related with
      body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship
      with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum
      glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF- alpha (r = 0.4717).
      Thus, serum levels of IL-12 are increased in overweight and obese individuals and
      show a strong relationship with markers of low-grade inflammation and obesity in
      the Mexican adult population. Further research is needed to understand the role
      of IL-12 in developing obesity-associated alterations in humans.

PMID- 23533316
TI  - Software safety in radiation therapy.

PMID- 23533317
TI  - From the Editor's desk.

PMID- 23533315
TI  - Low-grade inflammation and spinal cord injury: exercise as therapy?
AB  - An increase in the prevalence of obesity in people with spinal cord injury can
      contribute to low-grade chronic inflammation and increase the risk of infection
      in this population. A decrease in sympathetic activity contributes to
      immunosuppression due to the lower activation of immune cells in the blood. The
      effects of physical exercise on inflammatory parameters in individuals with
      spinal cord injury have not been well described. We conducted a review of the
      literature published from 1974 to 2012. This review explored the relationships
      between low-grade inflammation, spinal cord injury, and exercise to discuss a
      novel mechanism that might explain the beneficial effects of exercise involving
      an increase in catecholamines and cytokines in people with spinal cord injury.

PMID- 23533318
TI  - Pregnancy outcomes in HIV-infected women receiving long-term isoniazid
      prophylaxis for tuberculosis and antiretroviral therapy.
AB  - OBJECTIVE: While 6- to 12-month courses of isoniazid for tuberculosis prevention
      are considered safe in pregnant women, the effects of longer-term isoniazid
      prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not
      established in human-immunodeficiency-virus-(HIV-) infected women who experience
      pregnancy during the course of therapy. DESIGN: Nested study of pregnancy
      outcomes among HIV-infected women participating in a placebo-controlled, TB
      prevention trial using 36 months daily isoniazid. Pregnancy outcomes were
      collected by interview and record review. RESULTS: Among 196 pregnant women, 103
      (52.6%) were exposed to isoniazid during pregnancy; all were exposed to
      antiretroviral drugs. Prior to pregnancy they had received a median of 341 days
      (range 1-1095) of isoniazid. We observed no isoniazid-associated hepatitis or
      other severe isoniazid-associated adverse events in the 103 women. Pregnancy
      outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low
      birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital
      abnormality. In a multivariable model, neither isoniazid nor ART exposure during
      pregnancy was significantly associated with adverse pregnancy outcome (adjusted
      odds ratios 0.6, 95% CI: 0.3-1.1 and 1.8, 95% CI 0.9-3.6, resp.). CONCLUSIONS:
      Long-term isoniazid prophylaxis was not associated with adverse pregnancy
      outcomes, such as preterm delivery, even in the context of ART exposure.

PMID- 23533319
TI  - Endoscopic ultrasound-guided oncologic therapy for pancreatic cancer.
AB  - Since the development of endoscopic ultrasound-guided fine needle aspiration (EUS
      FNA) in the early 1990s, its application has been extended to various diseases.
      For pancreatic cancer, EUS-FNA can obtain specimens from the tumor itself with
      fewer complications than other methods. Interventional EUS enables various
      therapeutic options: local ablation, brachytherapy, placement of fiducial markers
      for radiotherapy, and direct injection of antitumor agents into cancer. This
      paper will focus on EUS-guided oncologic therapy for pancreatic cancer.

PMID- 23533321
TI  - Colonoscopy practice in lagos, Nigeria: a report of an audit.
AB  - Background. Colonoscopy effectiveness depends on the quality of the examination.
      Community-based report of quality of colonoscopy practice in a developing country
      will help in determining standard and also serve as a stimulus for improvement in
      service. Aim. To review the quality of colonoscopy practice and document pattern
      of colonic disease including polyp detection rate in Lagos, Nigeria. Method. A
      protocol that captured the patients' demographics, indication, and some quality
      indices of colonoscopy was developed and sent to all the identified colonoscopy
      units in Lagos to complete for all procedures performed between January 2011 and
      June 2012. All data were collated and analyzed. The quality indices studied were
      compared with guideline standard. Results. Twelve colonoscopy centers were
      identified but only nine centers responded. The gastroenterologist/endoscopists
      were physicians (3) and surgeons (5). Six hundred and seven colonoscopy
      procedures were performed during this period (M : F = 333 : 179) while the sex
      was not disclosed in 95 subjects. The examination indications were lower GI
      bleeding (24.2%), altered bowel habits (9.2%), lower abdominal pain (9.1%),
      screening for CRC (4.3%) and unspecified (46.8%). Conscious sedation was
      generally used while bowel preparation (good in 81.4%) was done with low residue
      diet and stimulant laxatives. Caecal intubation rate was 81.2%. Common endoscopic
      findings were haemorrhoids (43.2%), polyps/masses (13.4%), diverticulosis
      (11.1%), and no abnormality (23.4%). Polyp was detected in 6.8% of cases.
      Conclusion. Colonoscopy utilization is low, and the quality of practice is
      suboptimal; although limited resources could partly explain this, however it is
      not clear if the low rate of polyp detection is due to missed lesions or low
      population incidence.

PMID- 23533320
TI  - The current state of diagnosis and treatment for early gastric cancer.
AB  - The prognosis for gastric cancer depends on its stage; so, detection in the early
      stage of disease is important, when complete and curative removal is possible.
      Accurate diagnosis can be facilitated by a sound understanding of the basic
      findings of white light endoscopy of early gastric cancer, and diagnosis can be
      refined further by the combined use of other imaging modalities such as image
      enhanced endoscopy including chromoendoscopy and endoscopic ultrasonography.
      Minimally invasive endoscopic treatment has come to be the preferred therapeutic
      approach for early gastric cancer. In addition to conventional endoscopic mucosal
      resection, a new technique known as endoscopic submucosal dissection (ESD) has
      spread rapidly worldwide. Indeed, strategies for ESD have been established,
      devices developed, its indications expanded, and its safety and long-term results
      extensively reported. Some unique combination therapies involving endoscopy and
      surgical treatment have also been reported. It is anticipated that the number of
      patients undergoing endoscopic therapy will continue to increase, and the ongoing
      developments in endoscopic treatment are expected not only to improve gastric
      cancer prognosis but also to maintain good quality of life after treatment.

PMID- 23533322
TI  - Ethnicity, migration and minority groups: medicines access and use in high-income
      economies.

PMID- 23533323
TI  - The importance of medicines safety.

PMID- 23533324
TI  - Sustained Low-Dose Treatment with the Histone Deacetylase Inhibitor LBH589
      Induces Terminal Differentiation of Osteosarcoma Cells.
AB  - Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago
      based on their ability to induce cellular differentiation. However, the clinical
      development of these compounds as cancer therapies has focused on their capacity
      to induce apoptosis in hematologic and lymphoid malignancies, often in
      combination with conventional cytotoxic agents. In many cases, HDACi doses
      necessary to induce these effects result in significant toxicity. Since
      osteosarcoma cells express markers of terminal osteoblast differentiation in
      response to DNA methyltransferase inhibitors, we reasoned that the epigenetic
      reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here,
      we show that continuous exposure of osteosarcoma cells to low concentrations of
      HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast
      differentiation and irreversible senescence without inducing cell death.
      Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene
      signatures characteristic of chondrocyte and adipocyte lineages in addition to
      marked upregulation of mature osteoblast markers. In a mouse xenograft model,
      continuous low dose treatment with LBH589 induced a sustained cytostatic response
      accompanied by induction of mature osteoblast gene expression. These data suggest
      that the remarkable capacity of osteosarcoma cells to differentiate in response
      to HDACi therapy could be exploited for therapeutic benefit without inducing
      systemic toxicity.

PMID- 23533325
TI  - Erratum to "desmoid fibromatosis in pediatric patients: management based on a
      retrospective analysis of 59 patients and a review of the literature".

PMID- 23533326
TI  - Surgical guides (patient-specific instruments) for pediatric tibial bone sarcoma
      resection and allograft reconstruction.
AB  - To achieve local control of malignant pediatric bone tumors and to provide
      satisfactory oncological results, adequate resection margins are mandatory. The
      local recurrence rate is directly related to inappropriate excision margins. The
      present study describes a method for decreasing the resection margin width and
      ensuring that the margins are adequate. This method was developed in the tibia,
      which is a common site for the most frequent primary bone sarcomas in children.
      Magnetic resonance imaging (MRI) and computerized tomography (CT) were used for
      preoperative planning to define the cutting planes for the tumors: each tumor was
      segmented on MRI, and the volume of the tumor was coregistered with CT. After
      preoperative planning, a surgical guide (patient-specific instrument) that was
      fitted to a unique position on the tibia was manufactured by rapid prototyping. A
      second instrument was manufactured to adjust the bone allograft to fit the
      resection gap accurately. Pathologic evaluation of the resected specimens showed
      tumor-free resection margins in all four cases. The technologies described in
      this paper may improve the surgical accuracy and patient safety in surgical
      oncology. In addition, these techniques may decrease operating time and allow for
      reconstruction with a well-matched allograft to obtain stable osteosynthesis.

PMID- 23533328
TI  - Temporal and spatial coexistence of archaeal and bacterial amoA genes and gene
      transcripts in Lake Lucerne.
AB  - Despite their crucial role in the nitrogen cycle, freshwater ecosystems are
      relatively rarely studied for active ammonia oxidizers (AO). This study of Lake
      Lucerne determined the abundance of both amoA genes and gene transcripts of
      ammonia-oxidizing archaea (AOA) and bacteria (AOB) over a period of 16 months,
      shedding more light on the role of both AO in a deep, alpine lake environment. At
      the surface, at 42 m water depth, and in the water layer immediately above the
      sediment, AOA generally outnumbered AOB. However, in the surface water during
      summer stratification, when both AO were low in abundance, AOB were more numerous
      than AOA. Temporal distribution patterns of AOA and AOB were comparable. Higher
      abundances of amoA gene transcripts were observed at the onset and end of summer
      stratification. In summer, archaeal amoA genes and transcripts correlated
      negatively with temperature and conductivity. Concentrations of ammonium and
      oxygen did not vary enough to explain the amoA gene and transcript dynamics. The
      observed herbivorous zooplankton may have caused a hidden flux of mineralized
      ammonium and a change in abundance of genes and transcripts. At the surface, AO
      might have been repressed during summer stratification due to nutrient limitation
      caused by active phytoplankton.

PMID- 23533329
TI  - Crystal structure of PAV1-137: a protein from the virus PAV1 that infects
      Pyrococcus abyssi.
AB  - Pyrococcus abyssi virus 1 (PAV1) was the first virus particle infecting a
      hyperthermophilic Euryarchaeota (Pyrococcus abyssi strain GE23) that has been
      isolated and characterized. It is lemon shaped and is decorated with a short
      fibered tail. PAV1 morphologically resembles the fusiform members of the family
      Fuselloviridae or the genus Salterprovirus. The 18 kb dsDNA genome of PAV1
      contains 25 predicted genes, most of them of unknown function. To help assigning
      functions to these proteins, we have initiated structural studies of the PAV1
      proteome. We determined the crystal structure of a putative protein of 137
      residues (PAV1-137) at a resolution of 2.2 A. The protein forms dimers both in
      solution and in the crystal. The fold of PAV1-137 is a four- alpha -helical
      bundle analogous to those found in some eukaryotic adhesion proteins such as
      focal adhesion kinase, suggesting that PAV1-137 is involved in protein-protein
      interactions.

PMID- 23533330
TI  - Contribution of transcriptomics to systems-level understanding of methanogenic
      Archaea.
AB  - Methane-producing Archaea are of interest due to their contribution to
      atmospheric change and for their roles in technological applications including
      waste treatment and biofuel production. Although restricted to anaerobic
      environments, methanogens are found in a wide variety of habitats, where they
      commonly live in syntrophic relationships with bacterial partners. Owing to tight
      thermodynamic constraints of methanogenesis alone or in syntrophic metabolism,
      methanogens must carefully regulate their catabolic pathways including the
      regulation of RNA transcripts. The transcriptome is a dynamic and important
      control point in microbial systems. This paper assesses the impact of mRNA
      (transcriptome) studies on the understanding of methanogenesis with special
      consideration given to how methanogenesis is regulated to cope with nutrient
      limitation, environmental variability, and interactions with syntrophic partners.
      In comparison with traditional microarray-based transcriptome analyses, next
      generation high-throughput RNA sequencing is greatly advantageous in assessing
      transcription start sites, the extent of 5' untranslated regions, operonic
      structure, and the presence of small RNAs. We are still in the early stages of
      understanding RNA regulation but it is already clear that determinants beyond
      transcript abundance are highly relevant to the lifestyles of methanogens,
      requiring further study.

PMID- 23533332
TI  - Localization of Methyl-Coenzyme M reductase as metabolic marker for diverse
      methanogenic Archaea.
AB  - Methyl-Coenzyme M reductase (MCR) as key enzyme for methanogenesis as well as for
      anaerobic oxidation of methane represents an important metabolic marker for both
      processes in microbial biofilms. Here, the potential of MCR-specific polyclonal
      antibodies as metabolic marker in various methanogenic Archaea is shown. For
      standard growth conditions in laboratory culture, the cytoplasmic localization of
      the enzyme in Methanothermobacter marburgensis, Methanothermobacter wolfei,
      Methanococcus maripaludis, Methanosarcina mazei, and in anaerobically methane
      oxidizing biofilms is demonstrated. Under growth limiting conditions on nickel
      depleted media, at low linear growth of cultures, a fraction of 50-70% of the
      enzyme was localized close to the cytoplasmic membrane, which implies
      "facultative" membrane association of the enzyme. This feature may be also useful
      for assessment of growth-limiting conditions in microbial biofilms.

PMID- 23533333
TI  - From the Editor's Desk: Subvert the Dominant Paradigm; Think Outside the Box.

PMID- 23533334
TI  - Advancing evidence-based practice: a quarterly compilation of research updates
      most likely to change clinical practice.

PMID- 23533331
TI  - Mechanisms of metal resistance and homeostasis in haloarchaea.
AB  - Haloarchaea are the predominant microflora of hypersaline econiches such as solar
      salterns, soda lakes, and estuaries where the salinity ranges from 35 to 400 ppt.
      Econiches like estuaries and solar crystallizer ponds may contain high
      concentrations of metals since they serve as ecological sinks for metal pollution
      and also as effective traps for river borne metals. The availability of metals in
      these econiches is determined by the type of metal complexes formed and the
      solubility of the metal species at such high salinity. Haloarchaea have developed
      specialized mechanisms for the uptake of metals required for various key
      physiological processes and are not readily available at high salinity, beside
      evolving resistance mechanisms for metals with high solubility. The present paper
      seeks to give an overview of the main molecular mechanisms involved in metal
      tolerance in haloarchaea and focuses on factors such as salinity and metal
      speciation that affect the bioavailability of metals to haloarchaea. Global
      transcriptomic analysis during metal stress in these organisms will help in
      determining the various factors differentially regulated and essential for metal
      physiology.

PMID- 23533327
TI  - Microbial diversity and biochemical potential encoded by thermal spring
      metagenomes derived from the Kamchatka Peninsula.
AB  - Volcanic regions contain a variety of environments suitable for extremophiles.
      This study was focused on assessing and exploiting the prokaryotic diversity of
      two microbial communities derived from different Kamchatkian thermal springs by
      metagenomic approaches. Samples were taken from a thermoacidophilic spring near
      the Mutnovsky Volcano and from a thermophilic spring in the Uzon Caldera.
      Environmental DNA for metagenomic analysis was isolated from collected sediment
      samples by direct cell lysis. The prokaryotic community composition was examined
      by analysis of archaeal and bacterial 16S rRNA genes. A total number of 1235 16S
      rRNA gene sequences were obtained and used for taxonomic classification. Most
      abundant in the samples were members of Thaumarchaeota, Thermotogae, and
      Proteobacteria. The Mutnovsky hot spring was dominated by the Terrestrial Hot
      Spring Group, Kosmotoga, and Acidithiobacillus. The Uzon Caldera was dominated by
      uncultured members of the Miscellaneous Crenarchaeotic Group and
      Enterobacteriaceae. The remaining 16S rRNA gene sequences belonged to the
      Aquificae, Dictyoglomi, Euryarchaeota, Korarchaeota, Thermodesulfobacteria,
      Firmicutes, and some potential new phyla. In addition, the recovered DNA was used
      for generation of metagenomic libraries, which were subsequently mined for genes
      encoding lipolytic and proteolytic enzymes. Three novel genes conferring
      lipolytic and one gene conferring proteolytic activity were identified.

PMID- 23533335
TI  - Bioethics in practice: a quarterly column about medical ethics: stem cell ethics.

PMID- 23533338
TI  - CME Upcoming Events.

PMID- 23533337
TI  - Letters to the editor.

PMID- 23533336
TI  - Angiotensin and systems thinking: wrapping your mind around the big picture.

PMID- 23533339
TI  - CME Test/CME Application Form.

PMID- 23533340
TI  - Transcriptional regulation of fucosyltransferase 1 gene expression in colon
      cancer cells.
AB  - The alpha 1,2-fucosyltransferase I (FUT1) enzyme is important for the
      biosynthesis of H antigens, Lewis B, and Lewis Y. In this study, we clarified the
      transcriptional regulation of FUT1 in the DLD-1 colon cancer cell line, which has
      high expression of Lewis B and Lewis Y antigens, expresses the FUT1 gene, and
      shows alpha 1,2-fucosyltransferase (FUT) activity. 5'-rapid amplification of cDNA
      ends revealed a FUT1 transcriptional start site -10 nucleotides upstream of the
      site registered at NM_000148 in the DataBase of Human Transcription Start Sites
      (DBTSS). Using the dual luciferase assay, FUT1 gene expression was shown to be
      regulated at the region -91 to -81 nt to the transcriptional start site, which
      contains the Elk-1 binding site. Site-directed mutagenesis of this region
      revealed the Elk-1 binding site to be essential for FUT1 transcription.
      Furthermore, transfection of the dominant negative Elk-1 gene, and the chromatin
      immunoprecipitation (CHIp) assay, supported Elk-1-dependent transcriptional
      regulation of FUT1 gene expression in DLD-1 cells. These results suggest that a
      defined region in the 5'-flanking region of FUT1 is critical for FUT1
      transcription and that constitutive gene expression of FUT1 is regulated by Elk-1
      in DLD-1 cells.

PMID- 23533341
TI  - Quality of life in patients with minimal change nephrotic syndrome.
AB  - AIM: The goal of the study was to investigate quality of life (QOL) in adult
      patients with minimal change nephrotic syndrome (MCNS) and to test the
      relationship of QOL with the level of self-care. MATERIALS AND METHODS: We
      distributed two questionnaires to 30 outpatients with MCNS. The MOS 36-item Short
      Form Health Survey (SF-36v2) was used to examine health-related QOL in comparison
      with normative data from the general Japanese population and a population with
      two chronic diseases. SF-36v2 consists of 36 questions classified into 8
      subscales. We also used the Self-Care Behavior Scale for patients with chronic
      kidney disease (CKD), which consists of 31 questions with 4 subscales. RESULTS:
      The SF-36v2 social functioning subscale was most impaired and bodily pain was
      least affected in patients with MCNS. The self-care subscales of
      information/communication and positive behavior had positive correlations with
      the QOL subscales of mental health (P<0.05) and vitality (P<0.05). The
      correlation between social functioning and information/communication was close to
      significant (P=0.051). CONCLUSION: In MCNS, social functioning was particularly
      impaired. Our results suggest that better self-care can have a positive impact on
      QOL in patients with MCNS.

PMID- 23533343
TI  - Lateral access surgery for the thoracolumbar spine.

PMID- 23533342
TI  - Substrains of inbred mice differ in their physical activity as a behavior.
AB  - Recent studies strengthen the belief that physical activity as a behavior has a
      genetic basis. Screening wheel-running behavior in inbred mouse strains
      highlighted differences among strains, showing that even very limited genetic
      differences deeply affect mouse behavior. We extended this observation to
      substrains of the same inbred mouse strain, that is, BALB/c mice. We found that
      only a minority of the population of one of these substrains, the BALB/c J,
      performs spontaneous physical activity. In addition, the runners of this
      substrain cover a significantly smaller distance than the average runners of two
      other substrains, namely, the BALB/c ByJ and the BALB/c AnNCrl. The latter shows
      a striking level of voluntary activity, with the average distance run/day
      reaching up to about 12 kilometers. These runners are not outstanders, but they
      represent the majority of the population, with important scientific and economic
      fallouts to be taken into account during experimental planning. Spontaneous
      activity persists in pathological conditions, such as cancer-associated cachexia.
      This important amount of physical activity results in a minor muscle adaptation
      to endurance exercise over a three-week period; indeed, only a nonsignificant
      increase in NADH transferase+ fibers occurs in this time frame.

PMID- 23533344
TI  - Advances in energy conservation of China steel industry.
AB  - The course, technical progresses, and achievements of energy conservation of
      China steel industry (CSI) during 1980-2010 were summarized. Then, the paper
      adopted e-p method to analyze the variation law and influencing factors of energy
      consumptions of large- and medium-scale steel plants within different stages. It
      is pointed out that energy consumption per ton of crude steel has been almost one
      half lower in these thirty years, with 60% as direct energy conservation owing to
      the change of process energy consumption and 40% as indirect energy conservation
      attributed to the adjustment of production structure. Next, the latest research
      progress of some key common technologies in CSI was introduced. Also, the
      downtrend of energy consumption per ton of crude steel and the potential energy
      conservation for CSI during 2011-2025 were forecasted. Finally, it is indicated
      that the key topic of the next 15 years' research on the energy conservation of
      CSI is the synergistic operation of material flow and energy flow. It could be
      achieved by the comprehensive study on energy flow network optimization, such as
      production, allocation, utilization, recovery, reuse, and resource, according to
      the energy quantity, quality, and user demand following the first and second laws
      of thermodynamics.

PMID- 23533345
TI  - Protein detection with potentiometric aptasensors: a comparative study between
      polyaniline and single-walled carbon nanotubes transducers.
AB  - A comparison study on the performance characteristics and surface
      characterization of two different solid-contact selective potentiometric thrombin
      aptasensors, one exploiting a network of single-walled carbon nanotubes (SWCNTs)
      and the other the polyaniline (PANI), both acting as a transducing element, is
      described in this work. The molecular properties of both SWCNT and PANI surfaces
      have been modified by covalently linking thrombin binding aptamers as
      biorecognition elements. The two aptasensors are compared and characterized
      through potentiometry and electrochemical impedance spectroscopy (EIS) based on
      the voltammetric response of multiply charged transition metal cations (such as
      hexaammineruthenium, [Ru(NH3)6](3+)) bound electrostatically to the DNA probes.
      The surface densities of aptamers were accurately determined by the integration
      of the peak for the reduction of [Ru(NH3)6](3+) to [Ru(NH3)6](2+). The
      differences and the similarities, as well as the transduction mechanism, are also
      discussed. The sensitivity is calculated as 2.97 mV/decade and 8.03 mV/decade for
      the PANI and SWCNTs aptasensors, respectively. These results are in accordance
      with the higher surface density of the aptamers in the SWCNT potentiometric
      sensor.

PMID- 23533346
TI  - Physiological and biochemical responses of Ulva prolifera and Ulva linza to
      cadmium stress.
AB  - Responses of Ulva prolifera and Ulva linza to Cd(2+) stress were studied. We
      found that the relative growth rate (RGR), Fv/Fm, and actual photochemical
      efficiency of PSII (Yield) of two Ulvaspecies were decreased under Cd(2+)
      treatments, and these reductions were greater in U. prolifera than in U. linza.
      U. prolifera accumulated more cadmium than U. linza under Cd(2+) stress. While U.
      linza showed positive osmotic adjustment ability (OAA) at a wider Cd(2+) range
      than U. prolifera. U. linza had greater contents of N, P, Na(+), K(+), and amino
      acids than U. prolifera. A range of parameters (concentrations of cadmium,
      Ca(2+), N, P, K(+), Cl(-), free amino acids (FAAs), proline, organic acids and
      soluble protein, Fv/Fm, Yield, OAA, and K(+)/Na(+)) could be used to evaluate
      cadmium resistance in Ulva by correlation analysis. In accordance with the order
      of the absolute values of correlation coefficient, contents of Cd(2+) and K(+),
      Yield, proline content, Fv/Fm, FAA content, and OAA value of Ulva were more
      highly related to their adaptation to Cd(2+) than the other eight indices. Thus,
      U. linza has a better adaptation to Cd(2+) than U. prolifera, which was due
      mainly to higher nutrient content and stronger OAA and photosynthesis in U.
      linza.

PMID- 23533347
TI  - Improved tissue culture conditions for engineered skeletal muscle sheets.
AB  - The potential clinical utility of engineered muscle is currently restricted by
      limited in vitro capacity of expanded muscle precursor cells to fuse and form
      mature myofibers. The purpose of this study was to use isotropic skeletal muscle
      sheets to explore the impact of (1) fibroblast coculture and (2) fibroblast
      conditioned media (fCM) on in vitro myogenesis. Muscle sheets were prepared by
      seeding varying ratios of skeletal myoblasts and fibroblasts on a biomimetic
      substrate and culturing the resulting tissue in either control media or fCM.
      Muscle sheets were prepared from two cell subpopulations, (1) C2C12 and NOR-10
      and (2) primary neonatal rat skeletal muscle cells (nSKM). In C2C12/Nor-10 muscle
      sheets fCM conferred a myogenic advantage early in culture; at D1 a statistically
      significant 3.12 +/- 0.8-fold increase in myofiber density was observed with fCM.
      A high purity satellite cell population was collected from an initially mixed
      population of nSKMs via cell sorting for positive alpha 7-integrin expression. On
      D6, tissue sheets with low fibroblast concentrations (0 & 10%) cultured in fCM
      had increased average myofiber density (4.8 +/- 0.2 myofibers/field) compared to
      tissue sheets with high fibroblast concentrations (50%) cultured in control media
      (1.0 +/- 0.1 myofibers/field). Additionally, fCM promoted longer, thicker
      myofibers with a mature phenotype.

PMID- 23533348
TI  - Seasonality and dynamic spatial contagion of air pollution in 42 Chinese cities.
AB  - To monitor and improve the urban air quality, the Chinese government has begun to
      make many efforts, and the interregional cooperation to cut and improve air
      quality has been required. In this paper, we focus on the seasonality of the
      first and second moments of the daily air pollution indexes (APIs) of 42 Chinese
      sample cities over 10 years, from June 5, 2000 to March 4, 2010, and investigate
      the dynamic correlation of air pollution indexes (APIs) between 42 Chinese cities
      and their corresponding regional and national levels; comparison with the model
      without seasonal consideration is made. By adopting a DCC-GARCH model that
      accounts for the seasonality, we found that (i) the transformed DCC-GARCH model
      including seasonality dummies improves the estimation result in this study; (ii)
      the seasonality feature of the second moment follows that of the first moment,
      with the condition mean and variance of the second and autumn significantly lower
      than spring, whereas that of winter is higher than spring; (iii) the correlation
      between local APIs and their corresponding regional and national levels is
      dynamic; (iv) comparing with the DCC-GARCH model estimation, the transformed
      model does not change the feature of the dynamic correlations very much.

PMID- 23533349
TI  - VEGF promotes proliferation of human glioblastoma multiforme stem-like cells
      through VEGF receptor 2.
AB  - Cancer stem-like cells, which have been described as tumor-initiating cells or
      tumor-propagating cells, play a crucial role in our fundamental understanding of
      glioblastoma multiforme (GBM) and its recurrence. GBM is a lethal cancer,
      characterized by florid vascularization and aberrantly elevated vascular
      endothelial growth factor (VEGF). VEGF promotes tumorigenesis and angiogenesis of
      human GBM stem-like cells (GBSCs). However, whether and how VEGF contributes to
      GBSCs proliferation remain largely uncertain. In this study, human GBSCs were
      isolated from surgical specimens of glioblastoma and cultured in medium favored
      for stem cell growth. Neural Colony-Forming Cell Assay and ATP assay were
      performed to measure GBSC proliferation under normoxia (20% O2) and hypoxia (1%
      O2). Our observations demonstrate that exogenous VEGF stimulates GBSC
      proliferation in a dose-dependent manner via VEGF Receptor 2 (VEGFR2); while VEGF
      Receptor 1 (VEGFR1) has a negative feedback effect on VEGFR2 when cells were
      exposed to higher concentration of VEGF. These results suggest that suppressing
      VEGFR2-dependent GBSC proliferation is a potentially therapeutic strategy in GBM.

PMID- 23533351
TI  - Are preoperative Kattan and Stephenson nomograms predicting biochemical
      recurrence after radical prostatectomy applicable in the Chinese population?
AB  - PURPOSE: Kattan and Stephenson nomograms are based on the outcomes of patients
      with prostate cancer recruited in the USA, but their applicability to Chinese
      patients is yet to be validated. We aim at studying the predictive accuracy of
      these nomograms in the Chinese population. PATIENTS AND METHODS: A total of 408
      patients who underwent laparoscopic or open radical resection of prostate from
      1995 to 2009 were recruited. The preoperative clinical parameters of these
      patients were collected, and they were followed up regularly with PSA monitored.
      Biochemical recurrence was defined as two or more consecutive PSA levels >0.4
      ng/mL after radical resection of prostate or secondary cancer treatment. RESULTS:
      The overall observed 5-year and 10-year biochemical recurrence-free survival
      rates were 68.3% and 59.8%, which was similar to the predicted values by the
      Kattan and Stephenson nomograms, respectively. The results of our study achieved
      a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5
      years, 0.62, 10-years, 0.71). CONCLUSIONS: The incidence of prostate cancer in
      Hong Kong is increasing together with the patients' awareness of this disease.
      Despite the fact that Kattan nomograms were derived from the western population,
      it has been validated in our study to be useful in Chinese patients as well.

PMID- 23533350
TI  - Life cycle and suicidal behavior among women.
AB  - It is nowadays accepted that, independently of methodological issues, women
      commit fewer suicides than men but make more frequent attempts. Yet, female
      suicidal risk varies greatly along the lifetime and is linked to the most
      significant moments in it. A wide analysis of the existing literature was
      performed to provide a narrative description on the evolution of female suicidal
      rates from childhood to old age, considering the milestones in their life
      history. A detailed analysis of gender differences in suicidal behavior is key to
      establish preventive measures and priorities. More specific studies are needed to
      adapt future interventions on female suicide.

PMID- 23533352
TI  - A novel evaluation method for building construction project based on integrated
      information entropy with reliability theory.
AB  - Selecting construction schemes of the building engineering project is a complex
      multiobjective optimization decision process, in which many indexes need to be
      selected to find the optimum scheme. Aiming at this problem, this paper selects
      cost, progress, quality, and safety as the four first-order evaluation indexes,
      uses the quantitative method for the cost index, uses integrated qualitative and
      quantitative methodologies for progress, quality, and safety indexes, and
      integrates engineering economics, reliability theories, and information entropy
      theory to present a new evaluation method for building construction project.
      Combined with a practical case, this paper also presents detailed computing
      processes and steps, including selecting all order indexes, establishing the
      index matrix, computing score values of all order indexes, computing the
      synthesis score, sorting all selected schemes, and making analysis and decision.
      Presented method can offer valuable references for risk computing of building
      construction projects.

PMID- 23533353
TI  - DNA damage sensor gamma -H2AX is increased in preneoplastic lesions of
      hepatocellular carcinoma.
AB  - BACKGROUND: Phosphorylated histone H2AX ( gamma -H2AX) is a potential regulator
      of DNA repair and is a useful tool for detecting DNA damage. To evaluate the
      clinical usefulness of gamma -H2AX in hepatocellular carcinoma (HCC), we measured
      the level of gamma -H2AX in HCC, dysplastic nodule, and nontumorous liver
      diseases. METHODS: The level of gamma -H2AX was measured by immunohistochemistry
      in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic
      nodules. Appropriate cases were also examined by fluorescence analysis and
      western blotting. results: All cases with chronic liver disease showed increased
      levels of gamma -H2AX expression. In 40 (69.9%) of 58 cases with HCC, the
      labeling index (LI) of gamma -H2AX was above 50% and was inversely correlated
      with the histological grade. Mean gamma -H2AX LI was the highest in dysplastic
      nodule (74.1 +/- 22.1%), which was significantly higher than HCC (P < 0.005).
      Moreover, gamma -H2AX was significantly increased in nontumorous tissues of HCC
      as compared with liver cirrhosis without HCC (62.5 +/- 24.7%, from 5.1 to 96.0%,
      P < 0.005). CONCLUSIONS: gamma -H2AX was increased in the preneoplastic lesions
      of HCC and might be a useful biomarker for predicting the risk of HCC.

PMID- 23533354
TI  - Metal-enhanced fluorescence of chlorophylls in light-harvesting complexes coupled
      to silver nanowires.
AB  - We investigate metal-enhanced fluorescence of peridinin-chlorophyll protein
      coupled to silver nanowires using optical microscopy combined with spectrally and
      time-resolved fluorescence techniques. In particular we study two different
      sample geometries: first, in which the light-harvesting complexes are deposited
      onto silver nanowires, and second, where solution of both nanostructures are
      mixed prior deposition on a substrate. The results indicate that for the
      peridinin-chlorophyll complexes placed in the vicinity of the silver nanowires we
      observe higher intensities of fluorescence emission as compared to the reference
      sample, where no nanowires are present. Enhancement factors estimated for the
      sample where the light-harvesting complexes are mixed together with the silver
      nanowires prior deposition on a substrate are generally larger in comparison to
      the other geometry of a hybrid nanostructure. While fluorescence spectra are
      identical both in terms of overall shape and maximum wavelength for peridinin
      chlorophyll-protein complexes both isolated and coupled to metallic
      nanostructures, we conclude that interaction with plasmon excitations in the
      latter remains neutral to the functionality of the biological system.
      Fluorescence transients measured for the PCP complexes coupled to the silver
      nanowires indicate shortening of the fluorescence lifetime pointing towards
      modifications of radiative rate due to plasmonic interactions. Our results can be
      applied for developing ways to plasmonically control the light-harvesting
      capability of photosynthetic complexes.

PMID- 23533356
TI  - Genome-wide analysis of DNA methylation in human amnion.
AB  - The amnion is a specialized tissue in contact with the amniotic fluid, which is
      in a constantly changing state. To investigate the importance of epigenetic
      events in this tissue in the physiology and pathophysiology of pregnancy, we
      performed genome-wide DNA methylation profiling of human amnion from term (with
      and without labor) and preterm deliveries. Using the Illumina Infinium
      HumanMethylation27 BeadChip, we identified genes exhibiting differential
      methylation associated with normal labor and preterm birth. Functional analysis
      of the differentially methylated genes revealed biologically relevant enriched
      gene sets. Bisulfite sequencing analysis of the promoter region of the oxytocin
      receptor (OXTR) gene detected two CpG dinucleotides showing significant
      methylation differences among the three groups of samples. Hypermethylation of
      the CpG island of the solute carrier family 30 member 3 (SLC30A3) gene in preterm
      amnion was confirmed by methylation-specific PCR. This work provides preliminary
      evidence that DNA methylation changes in the amnion may be at least partially
      involved in the physiological process of labor and the etiology of preterm birth
      and suggests that DNA methylation profiles, in combination with other biological
      data, may provide valuable insight into the mechanisms underlying normal and
      pathological pregnancies.

PMID- 23533357
TI  - The aquatic environment as a reservoir of Vibrio cholerae O1 in hydrographic
      basins of the state of Pernambuco, Brazil.
AB  - After the worldwide cholera epidemic in 1993, permanent environmental monitoring
      of hydrographic basins was established in Pernambuco, Brazil, where cholera is
      endemic. After a quiescent period, 4 rfbN (serogroup O1) positive water samples
      that were culture negative were detected by multiplex single-tube nested PCR
      (MSTNPCR); 2 of these were also ctxA (cholera toxin) positive. From May to June
      2012, 30 V. cholerae O1 isolates were obtained by culturing samples. These
      isolates were analyzed for the presence of virulence genes by PCR, intergenic
      spacer region 16S-23S PCR (ISR-PCR), and pulsed field gel electrophoresis (PFGE).
      The isolates were positive for the rfbN gene and negative for the assessed
      pathogenic genes and were classified into 2 groups by ISR and the same profile by
      PFGE. Close genetic similarity was observed between them (2012) and environmental
      strains from 2004 to 2005, indicating the permanence of endemic V. cholerae O1 in
      the region.

PMID- 23533359
TI  - Music identification system using MPEG-7 audio signature descriptors.
AB  - This paper describes a multiresolution system based on MPEG-7 audio signature
      descriptors for music identification. Such an identification system may be used
      to detect illegally copied music circulated over the Internet. In the proposed
      system, low-resolution descriptors are used to search likely candidates, and then
      full-resolution descriptors are used to identify the unknown (query) audio. With
      this arrangement, the proposed system achieves both high speed and high accuracy.
      To deal with the problem that a piece of query audio may not be inside the
      system's database, we suggest two different methods to find the decision
      threshold. Simulation results show that the proposed method II can achieve an
      accuracy of 99.4% for query inputs both inside and outside the database. Overall,
      it is highly possible to use the proposed system for copyright control.

PMID- 23533355
TI  - The emerging role of complement lectin pathway in trypanosomatids: molecular
      bases in activation, genetic deficiencies, susceptibility to infection, and
      complement system-based therapeutics.
AB  - The innate immune system is evolutionary and ancient and is the pivotal line of
      the host defense system to protect against invading pathogens and abnormal self
      derived components. Cellular and molecular components are involved in recognition
      and effector mechanisms for a successful innate immune response. The complement
      lectin pathway (CLP) was discovered in 1990. These new components at the
      complement world are very efficient. Mannan-binding lectin (MBL) and ficolin not
      only recognize many molecular patterns of pathogens rapidly to activate
      complement but also display several strategies to evade innate immunity. Many
      studies have shown a relation between the deficit of complement factors and
      susceptibility to infection. The recently discovered CLP was shown to be
      important in host defense against protozoan microbes. Although the recognition of
      pathogen-associated molecular patterns by MBL and Ficolins reveal efficient
      complement activations, an increase in deficiency of complement factors and
      diversity of parasite strategies of immune evasion demonstrate the unsuccessful
      effort to control the infection. In the present paper, we will discuss basic
      aspects of complement activation, the structure of the lectin pathway components,
      genetic deficiency of complement factors, and new therapeutic opportunities to
      target the complement system to control infection.

PMID- 23533358
TI  - NCK2 is significantly associated with opiates addiction in African-origin men.
AB  - Substance dependence is a complex environmental and genetic disorder with
      significant social and medical concerns. Understanding the etiology of substance
      dependence is imperative to the development of effective treatment and prevention
      strategies. To this end, substantial effort has been made to identify genes
      underlying substance dependence, and in recent years, genome-wide association
      studies (GWASs) have led to discoveries of numerous genetic variants for complex
      diseases including substance dependence. Most of the GWAS discoveries were only
      based on single nucleotide polymorphisms (SNPs) and a single dichotomized
      outcome. By employing both SNP- and gene-based methods of analysis, we identified
      a strong (odds ratio = 13.87) and significant (P value = 1.33E - 11) association
      of an SNP in the NCK2 gene on chromosome 2 with opiates addiction in African
      origin men. Codependence analysis also identified a genome-wide significant
      association between NCK2 and comorbidity of substance dependence (P value = 3.65E
      - 08) in African-origin men. Furthermore, we observed that the association
      between the NCK2 gene (P value = 3.12E - 10) and opiates addiction reached the
      gene-based genome-wide significant level. In summary, our findings provided the
      first evidence for the involvement of NCK2 in the susceptibility to opiates
      addiction and further revealed the racial and gender specificities of its impact.

PMID- 23533360
TI  - From ontology to semantic similarity: calculation of ontology-based semantic
      similarity.
AB  - Advances in high-throughput experimental techniques in the past decade have
      enabled the explosive increase of omics data, while effective organization,
      interpretation, and exchange of these data require standard and controlled
      vocabularies in the domain of biological and biomedical studies. Ontologies, as
      abstract description systems for domain-specific knowledge composition, hence
      receive more and more attention in computational biology and bioinformatics.
      Particularly, many applications relying on domain ontologies require quantitative
      measures of relationships between terms in the ontologies, making it
      indispensable to develop computational methods for the derivation of ontology
      based semantic similarity between terms. Nevertheless, with a variety of methods
      available, how to choose a suitable method for a specific application becomes a
      problem. With this understanding, we review a majority of existing methods that
      rely on ontologies to calculate semantic similarity between terms. We classify
      existing methods into five categories: methods based on semantic distance,
      methods based on information content, methods based on properties of terms,
      methods based on ontology hierarchy, and hybrid methods. We summarize
      characteristics of each category, with emphasis on basic notions, advantages and
      disadvantages of these methods. Further, we extend our review to software tools
      implementing these methods and applications using these methods.

PMID- 23533361
TI  - Proximal femoral nail versus dynamic hip screw fixation for trochanteric
      fractures: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The purpose of this meta-analysis was to find out whether the
      proximal femoral nail was better than the dynamic hip screw in the treatment of
      trochanteric fractures with respect to operation time, blood transfusion,
      hospital stay, wound complications, number of reoperation, and mortality rate.
      METHODS: All randomized controlled trials comparing proximal femoral nail and
      dynamic hip screw in the treatment of trochanteric fractures were included.
      Articles and conference data were extracted by two authors independently. Data
      was analyzed using RevMan 5.1 version. Eight trials involving 1348 fractures were
      retrieved. RESULTS: Compared with DHS fixation, PFN fixation had similar
      operation time (95% CI: -15.28-2.40, P = 0.15). Blood loss and transfusion during
      perioperative time were also comparable between the two fixations (95% CI: 
      301.39-28.11, P = 0.10; 95% CI: -356.02-107.20, P = 0.29, resp.). Outcomes of
      hospital stay (95% CI: -0.62-1.01, P = 0.64), wound complication (95% CI: 0.66
      1.67, P = 0.82), mortality (95% CI: 0.83-1.30, P = 0.72), and reoperation (95%
      CI: 0.61-1.54, P = 0.90) were all similar between the two groups. CONCLUSION: PFN
      fixation shows the same effectiveness as DHS fixation in the parameters measured.

PMID- 23533362
TI  - Comparison of soft tissue cephalometric norms between Turkish and European
      American adults.
AB  - One of the most important components of orthodontic diagnosis and treatment
      planning is the evaluation of the patient's soft tissue profile. The main purpose
      of this study was to develop soft-tissue cephalometric standards for Turkish men
      and women and compare them with the cephalometric standards of normal European
      American white people. The sample included 96 Turkish adults (48 women, 48 men),
      aged 20 to 27 years. Turkish subjects have increased facial convexity associated
      with retruded mandible, more obtuse lower face-throat angle, increased nasolabial
      angle and upper lip protrusion, deeper mentolabial sulcus, and smaller
      interlabial gap compared with European-American white people. It is appropriate
      to consider these differences during routine diagnosis and treatment planning of
      a Turkish patient or an American patient of European ancestry. Turkish males
      reveal more obtuse mandibular prognathism and upper lip protrusion, and smaller
      nasolabial angle than females.

PMID- 23533363
TI  - Levels of organochlorine pesticides and heavy metals in surface waters of Konya
      closed basin, Turkey.
AB  - The concentrations of organochlorine pesticides (OCPs), including alpha -, beta 
      , gamma -, and delta -hexachlorocyclohexane (HCH), heptachlor, heptachlor
      epoxide, dieldrin, aldrin, endrin, endrin aldehyde, endrin ketone, endosulfan I,
      endosulfan II, endosulfan sulfate, p,p'-DDE, p,p'-DDD, p,p'-DDT, methoxychlor,
      chlordane I, chlordane II, and heavy metals, such as As, Cr, Cu, Fe, Mn, and Ni
      in surface water samples from the Konya closed basin were determined to evaluate
      the level of contamination. Among all HCH isomers, beta -HCH is the main isomer
      with a concentration range of 0.015-0.065 MU g/L. DDE, DDD, and DDT were almost
      determined in all samples, in which DDE isomer had the highest concentration
      ranged from not detected to 0.037 MU g/L. In all studied OCPs, aldrin showed the
      highest concentration at 0.220 MU g/L. The concentrations of heavy metals in
      water samples were observed with order: Mn<Cu<Ni<As<Cr<Fe. In some samples, As,
      Fe, and Cr concentrations exceeded the drinking water quality recommended by EU,
      US EPA, WHO, and Turkish Regulation, while Cu, Ni, and Mn concentrations are
      below the guideline values. The levels of both OCPs and heavy metals were also
      compared with other previously published data.

PMID- 23533364
TI  - Friction forces during sliding of various brackets for malaligned teeth: an in
      vitro study.
AB  - AIMS: To measure the friction force generated during sliding mechanics with
      conventional, self-ligating (Damon 3 mx, Smart Clip, and Time 3) and low-friction
      (Synergy) brackets using different archwire diameters and ligating systems in the
      presence of apical and buccal malalignments of the canine. METHODS: An
      experimental setup reproducing the right buccal segment of the maxillary arch was
      designed to measure the friction force generated at the bracket/wire and
      wire/ligature interfaces of different brackets. A complete factorial plan was
      drawn up and a three-way analysis of variance (ANOVA) was carried out to
      investigate whether the following factors affect the values of friction force:
      (i) degree of malalignment, (ii) diameter of the orthodontic wire, and (iii)
      bracket/ligature combination. Tukey post hoc test was also conducted to evaluate
      any statistically significant differences between the bracket/ligature
      combinations analyzed. RESULTS: ANOVA showed that all the above factors affect
      the friction force values. The friction force released during sliding mechanics
      with conventional brackets is about 5-6times higher than that released with the
      other investigated brackets. A quasilinear increase of the frictional forces was
      observed for increasing amounts of apical and buccal malalignments. CONCLUSION:
      The Synergy bracket with silicone ligature placed around the inner tie-wings
      appears to yield the best performance.

PMID- 23533365
TI  - BrdU pulse labelling in vivo to characterise cell proliferation during
      regeneration and repair following injury to the airway wall in sheep.
AB  - The response of S-phase cells labelled with bromodeoxyuridine (BrdU) in sheep
      airways undergoing repair in response to endobronchial brush biopsy was
      investigated in this study. Separate sites within the airway tree of
      anaesthetised sheep were biopsied at intervals prior to pulse labelling with
      BrdU, which was administered one hour prior to euthanasia. Both brushed and
      spatially disparate unbrushed (control) sites were carefully mapped, dissected,
      and processed to facilitate histological analysis of BrdU labelling. Our study
      indicated that the number and location of BrdU-labelled cells varied according to
      the age of the repairing injury. There was little evidence of cell proliferation
      in either control airway tissues or airway tissues examined six hours after
      injury. However, by days 1 and 3, BrdU-labelled cells were increased in number in
      the airway wall, both at the damaged site and in the regions flanking either side
      of the injury. Thereafter, cell proliferative activity largely declined by day 7
      after injury, when consistent evidence of remodelling in the airway wall could be
      appreciated. This study successfully demonstrated the effectiveness of in vivo
      pulse labelling in tracking cell proliferation during repair which has a
      potential value in exploring the therapeutic utility of stem cell approaches in
      relevant lung disease models.

PMID- 23533366
TI  - Design and performance evaluation of a rotary magnetorheological damper for
      unmanned vehicle suspension systems.
AB  - We designed and validated a rotary magnetorheological (MR) damper with a
      specified damping torque capacity, an unsaturated magnetic flux density (MFD),
      and a high magnetic field intensity (MFI) for unmanned vehicle suspension
      systems. In this study, for the rotary type MR damper to have these satisfactory
      performances, the roles of the sealing location and the cover case curvature of
      the MR damper were investigated by using the detailed 3D finite element model to
      reflect asymmetrical shapes and sealing components. The current study also
      optimized the damper cover case curvature based on the MFD, the MFI, and the
      weight of the MR damper components. The damping torques, which were computed
      using the characteristic equation of the MR fluid and the MFI of the MR damper,
      were 239.2, 436.95, and 576.78 N.m at currents of 0.5, 1, and 1.5 A,
      respectively, at a disk rotating speed of 10 RPM. These predicted damping torques
      satisfied the specified damping torque of 475 N.m at 1.5 A and showed errors of
      less than 5% when compared to experimental measurements from the MR damper
      manufactured by the proposed design. The current study could play an important
      role in improving the performance of rotary type MR dampers.

PMID- 23533367
TI  - Gene therapy with HSV1-sr39TK/GCV exhibits a stronger therapeutic efficacy than
      HSV1-TK/GCV in rat C6 glioma cells.
AB  - Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase
      (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment
      strategy for glioma, the almost immunodepressive dose of GCV required for its
      adequate in vivo efficacy has hampered its further clinical application.
      Therefore, In order to reduce the GCV dose required, we aim to compare the
      therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug
      catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6
      glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively,
      and the gene transfection efficacy was verified by immunocytochemistry and
      western blot analysis. Then the in vivo sensitivity of these transfected C6-TK
      and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)
      3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium
      iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was
      established in the nude mice to test the in vitro efficacy of TK/GCV gene
      therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV
      demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and
      in vivo, which, by reducing the required GCV dose, might warrant its future use
      in the treatment of glioma under clinical setting.

PMID- 23533368
TI  - MDCT in the differentiation of adrenal masses: comparison between different scan
      delays for the evaluation of intralesional washout.
AB  - PURPOSE: To evaluate the accuracy of the washout in the differential diagnosis
      between adenomas and nonadenomas and to compare the obtained results in delayed
      CT scans at 5, 10 and 15 minutes. METHODS: Fifty patients with adrenal masses
      were prospectively evaluated. CT scans were performed by using a 320-row MDCT
      device, before and after injection of contrast material. In 25 cases, delayed
      scans were performed at 5' and 10' (group 1), while in the remaining 25, at 5'
      and 15' (group 2). Absolute and relative wash-out percentage values (APW and RPW)
      were calculated. RESULTS: Differential diagnosis between adenomas and nonadenomas
      was obtained in 48/50 (96%) cases, with sensitivity, specificity, and accuracy
      values of 96%, 95%, and 96%, respectively. In group 1, APW and RPW values were,
      respectively, 69.8% and 67.2% at 5' and 75.9% and 73.5% at 10' for adenomas and
      25.1% and 15.8% at 5' and 33.5% and 20.5% at 10' for nonadenomas. In group 2, APW
      and RPW values were 63% and 54.6% at 5' and 73.8% and 65.5% at 15' for adenomas
      and 22% and 12.5% at 5' and 35.5% and 19.9% at 15' for nonadenomas. CONCLUSIONS:
      The evaluation of the wash-out values in CT scans performed at 5', 10', and 15'
      provides comparable diagnostic results. CT scans performed at 5' are, therefore,
      to be preferred, since they reduce the examination time and patient discomfort.

PMID- 23533369
TI  - Laparoscopic radical prostatectomy: the learning curve of a low volume surgeon.
AB  - OBJECTIVE: Analyze the learning curve for laparoscopic radical prostatectomy in a
      low volume program. MATERIALS AND METHODS: A single surgeon operated on 165
      patients. Patients were consecutively divided in 3 groups of 55 patients (groups
      A, B, and C). An enhancement of estimated blood loss, surgery length, and
      presence of a positive surgical margin were all considered as a function of
      surgeon's experience. RESULTS: Operative time was 267 minutes for group A, 230
      minutes for group B, and 159 minutes for group C, and the operative time
      decreased over time, but a significant difference was present only between groups
      A and C (P < 0.001). Mean estimated blood loss was 328 mL, 254 mL, and 206 mL (P
      = 0.24). A conversion to open surgery was necessary in 4 patients in group A.
      Positive surgical margin rates were 29.1%, 21.8%, and 5.5% (P = 0.02). Eight
      patients in group A, 4 patients in group B, and one in group C had biochemical
      recurrence. CONCLUSION: Significantly less intraoperative complications were
      evident after the first 51 cases. All other parameters (blood loss, operative
      time, and positive surgical margins) significantly decreased and stabilized after
      110 cases. Those outcomes were somehow similar to previous published series by
      high-volume centers.

PMID- 23533370
TI  - Evolving digital ecological networks.
AB  - "It is hard to realize that the living world as we know it is just one among many
      possibilities" [1]. Evolving digital ecological networks are webs of interacting,
      self-replicating, and evolving computer programs (i.e., digital organisms) that
      experience the same major ecological interactions as biological organisms (e.g.,
      competition, predation, parasitism, and mutualism). Despite being computational,
      these programs evolve quickly in an open-ended way, and starting from only one or
      two ancestral organisms, the formation of ecological networks can be observed in
      real-time by tracking interactions between the constantly evolving organism
      phenotypes. These phenotypes may be defined by combinations of logical
      computations (hereafter tasks) that digital organisms perform and by expressed
      behaviors that have evolved. The types and outcomes of interactions between
      phenotypes are determined by task overlap for logic-defined phenotypes and by
      responses to encounters in the case of behavioral phenotypes. Biologists use
      these evolving networks to study active and fundamental topics within
      evolutionary ecology (e.g., the extent to which the architecture of multispecies
      networks shape coevolutionary outcomes, and the processes involved).

PMID- 23533371
TI  - Preparation and Characterization of Hydroxyapatite Coating on AZ31 Mg Alloy for
      Implant Applications.
AB  - Magnesium alloys as biodegradable metal implants in orthopaedic research received
      a lot of interest in recent years. They have attractive biological properties
      including being essential to human metabolism, biocompatibility, and
      biodegradability. However, magnesium can corrode too rapidly in the high-chloride
      environment of the physiological system, loosing mechanical integrity before the
      tissue has sufficiently healed. Hydroxyapatite (HAp) coating was proposed to
      decrease the corrosion rate and improve the bioactivity of magnesium alloy.
      Apatite has been cathodically deposited on the surface of Mg alloy from solution
      that composed of 3 mM Ca(H2PO4)2 and 7 mM CaCl2 at various applied potentials.
      The growing of HAp was confirmed on the surface of the coatings after immersion
      in SBF solution for 7 days. The coating obtained at -1.4 V showed higher
      corrosion resistance with bioactive behaviors.

PMID- 23533372
TI  - Synthesis, CP-MAS NMR Characterization, and Antibacterial Activities of Glycine
      and Histidine Complexes of Cd(SeCN) 2 and Hg(SeCN) 2.
AB  - The synthesis and characterization of cadmium and mercury complexes of
      selenocyanate of the type [(L)M(SeCN)2] are described, where L is L-Histidine
      (His) or L-Glycine (Gly) and M is Cd(2+) or Hg(2+). These complexes are obtained
      by the reaction of 1 equivalent of respective amino acids with metal
      diselenocyanate precursor in a mixture of solvents (methanol : water = 1 : 1).
      These synthesized compounds are characterized by analytical and various
      spectroscopic techniques such as elemental analysis (EA), IR, H,1 and C13 NMR in
      solution and in the solid state for C13 and N15. The in vitro antibacterial
      activities of these complexes have been investigated with standard type cultures
      of Escherichia coli (MTCC 443), Klebsiella pneumoniae (MTCC 109), Pseudomonas
      aeruginosa (MTCC 1688), Salmonella typhi (MTCC 733), and Staphylococcus aureus
      (MTCC 737).

PMID- 23533373
TI  - Synthesis, Characterization, and Interaction with Biomolecules of Platinum(II)
      Complexes with Shikimic Acid-Based Ligands.
AB  - Starting from the active ingredient shikimic acid (SA) of traditional Chinese
      medicine and NH2(CH2) n OH, (n = 2-6), we have synthesized a series of new water
      soluble Pt(II) complexes PtL(a-e)Cl2, where L(a-e) are chelating diamine ligands
      with carbon chain covalently attached to SA (L(a-e) = SA-NH(CH2) n NHCH2CH2NH2;
      L(a), n = 2; L(b), n = 3; L(c), n = 4; L(d), n = 5; L(e), n = 6). The results of
      the elemental analysis, LC-MS, capillary electrophoresis, and (1)H, (13)C NMR
      indicated that there was only one product (isomer) formed under the present
      experimental conditions, in which the coordinate mode of PtL(a-e)Cl2 was two
      amine bidentate. Their in vitro cytotoxic activities were evaluated by MTT
      method, where these compounds only exhibited low cytotoxicity towards BEL7404,
      which should correlate their low lipophilicity. The interactions of the five
      Pt(II) complexes with DNA were investigated by agarose gel electrophoresis, which
      suggests that the Pt(II) complexes could induce DNA alteration. We also studied
      the interactions of the Pt(II) complexes with 5'-GMP with ESI-MS and (1)H NMR and
      found that PtL(b)Cl2, PtL(c)Cl2, and PtL(d)Cl2 could react with 5'-GMP to form
      mono-GMP and bis-GMP adducts. Furthermore, the cell-cycle analysis revealed that
      PtL(b)Cl2, PtL(c)Cl2 cause cell G2-phase arrest after incubation for 72 h.
      Overall, these water-soluble Pt(II) complexes interact with DNA mainly through
      covalent binding, which blocks the DNA synthesis and replication and thus induces
      cytotoxicity that weakens as the length of carbon chain increases.

PMID- 23533374
TI  - Reversing autism by targeting downstream mTOR signaling.

PMID- 23533375
TI  - Amyotrophic lateral sclerosis: a dying motor unit?

PMID- 23533376
TI  - BRCA-1 and BRCA-2 mutation bedside detection and breast cancer clinical primary
      prevention.

PMID- 23533378
TI  - Lung imaging data analysis.

PMID- 23533377
TI  - Molecular imaging probes for diagnosis and therapy evaluation of breast cancer.
AB  - Breast cancer is a major cause of cancer death in women where early detection and
      accurate assessment of therapy response can improve clinical outcomes. Molecular
      imaging, which includes PET, SPECT, MRI, and optical modalities, provides
      noninvasive means of detecting biological processes and molecular events in vivo.
      Molecular imaging has the potential to enhance our understanding of breast cancer
      biology and effects of drug action during both preclinical and clinical phases of
      drug development. This has led to the identification of many molecular imaging
      probes for key processes in breast cancer. Hormone receptors, growth factor
      receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been
      adopted as imaging targets to detect and stage the breast cancer and to monitor
      the treatment efficacy. Receptor imaging probes are usually composed of targeting
      moiety attached to a signaling component such as a radionuclide that can be
      detected using dedicated instruments. Current molecular imaging probes involved
      in breast cancer diagnosis and therapy evaluation are reviewed, and future of
      molecular imaging for the preclinical and clinical is explained.

PMID- 23533379
TI  - Doxorubicin-Induced Cardiac Toxicity Is Mediated by Lowering of Peroxisome
      Proliferator-Activated Receptor delta Expression in Rats.
AB  - The present study investigates the changes of peroxisome proliferator-activated
      receptors delta (PPAR delta ) expression and troponin phosphorylation in heart of
      rats which were treated with doxorubicin (DOX). Wistar rats which were treated
      with DOX according to a previous method. The protein levels of PPAR delta and
      troponin phosphorylation were measured using Western blot. The PPAR delta
      expression in heart was markedly reduced in DOX-treated rats showing a marked
      decrease in cardiac dP/dT and cardiac output. Also, cardiac troponin
      phosphorylation was lowered in DOX-treated rats. Meanwhile, combined treatment
      with the agonist of PPAR delta (GW0742) reversed the decrease of cardiac dP/dT
      and cardiac output in DOX-treated rats. Then, primary cultured cardiomyocytes
      from neonatal rats were used to measure the changes of calcium concentration in
      cells. In addition to both decrease of PPAR delta expression and troponin
      phosphorylation in neonatal cardiomyocytes by DOX, a marked decrease of calcium
      concentration was also observed. Our results suggest the mediation of cardiac
      PPAR delta in DOX-induced cardiotoxicity in rats. Thus, activation of PPAR delta
      may restore the expression of p-TnI and the cardiac performance in DOX-induced
      cardio toxicity in rats.

PMID- 23533381
TI  - Combined Effects of PPAR gamma Agonists and Epidermal Growth Factor Receptor
      Inhibitors in Human Proximal Tubule Cells.
AB  - We aimed to determine whether epidermal growth factor receptor (EGFR) inhibition,
      in addition to a peroxisome proliferator-activated receptor gamma (PPAR gamma )
      agonist, prevents high-glucose-induced proximal tubular fibrosis, inflammation,
      and sodium and water retention in human proximal tubule cells exposed to normal
      glucose; high glucose; high glucose with the PPAR gamma agonist pioglitazone or
      with the P-EGFR inhibitor, gefitinib; or high glucose with both pioglitazone and
      gefitinib. We have shown that high glucose increases AP-1 and NF kappa B binding
      activity, downstream phosphorylation of EGFR and Erk1/2, and fibronectin and
      collagen IV expression. Pioglitazone reversed these effects but upregulated NHE3
      and AQP1 expression. Gefitinib inhibited high glucose induced fibronectin and
      collagen IV, and EGFR and Erk1/2 phosphorylation and reversed pioglitazone
      induced increases in NHE3 and AQP1 expression. Our data suggests that combination
      of an EGFR inhibitor and a PPAR gamma agonist mitigates high-glucose-induced
      fibrosis and inflammation and reverses the upregulation of transporters and
      channels involved in sodium and water retention in human proximal tubule cells.
      Hence EGFR blockade may hold promise, not only in limiting tubulointerstitial
      pathology in diabetic nephropathy, but also in limiting the sodium and water
      retention observed in patients with diabetes and exacerbated by PPAR gamma
      agonists.

PMID- 23533380
TI  - Inhibitors of Fatty Acid Synthesis Induce PPAR alpha -Regulated Fatty Acid beta 
      Oxidative Genes: Synergistic Roles of L-FABP and Glucose.
AB  - While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase
      inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the
      mechanism of action is not simply accounted for by inhibition of the enzymes
      alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty
      acid signaling to peroxisome proliferator-activated receptor- alpha (PPAR alpha )
      in the nucleus, was found to bind TOFA and its activated CoA thioester, TOFyl
      CoA, with high affinity while binding C75 and C75-CoA with lower affinity.
      Binding of TOFA and C75-CoA significantly altered L-FABP secondary structure.
      High (20 mM) but not physiological (6 mM) glucose conferred on both TOFA and C75
      the ability to induce PPAR alpha transcription of the fatty acid beta -oxidative
      enzymes CPT1A, CPT2, and ACOX1 in cultured primary hepatocytes from wild-type
      (WT) mice. However, L-FABP gene ablation abolished the effects of TOFA and C75 in
      the context of high glucose. These effects were not associated with an increased
      cellular level of unesterified fatty acids but rather by increased intracellular
      glucose. These findings suggested that L-FABP may function as an intracellular
      fatty acid synthesis inhibitor binding protein facilitating TOFA and C75-mediated
      induction of PPAR alpha in the context of high glucose at levels similar to those
      in uncontrolled diabetes.

PMID- 23533382
TI  - Regulation effect of zinc fingers and homeoboxes 2 on alpha-fetoprotein in human
      hepatocellular carcinoma.
AB  - Aim. To investigate the relationship between alpha-fetoprotein and zinc fingers
      and homeoboxes 2 in hepatocellular carcinoma. Materials and Methods. The
      expressions of zinc fingers and homeoboxes 2, nuclear factor-YA, and alpha
      fetoprotein mRNA in 63 hepatocellular carcinoma were detected by reverse
      transcriptase-polymerase chain reaction and compared with the clinical parameters
      of the patients. Selectively, silence of zinc fingers and homeoboxes 2 in HepG2
      cells was detected by RNA interference technique. Results. Alpha-fetoprotein mRNA
      expression was detected in 60.3% of hepatocellular carcinoma cases. Zinc fingers
      and homeoboxes 2 mRNA expression (36.5%) was significantly negatively correlated
      with serum alpha-fetoprotein concentration and mRNA expression. A strong positive
      correlation was found between zinc fingers and homeoboxes 2 and nuclear factor-YA
      mRNA expression (42.9%), while the latter was negatively correlated with serum
      alpha-fetoprotein concentration and mRNA expression. Treatment with zinc fingers
      and homeoboxes 2 small interfering RNA led to 85% and 83% silence of zinc fingers
      and homeoboxes 2 mRNA and protein expression and 60% and 61% reduction of nuclear
      factor-YA mRNA and protein levels in the HepG2 cells, respectively.
      Downregulation of zinc fingers and homeoboxes 2 also induced a 2.4-fold increase
      in both alpha-fetoprotein mRNA and protein levels. Conclusions. Zinc fingers and
      homeoboxes 2 can regulate alpha-fetoprotein expression via the interaction with
      nuclear factor-YA in human hepatocellular carcinoma and may be used as an
      adjuvant diagnostic marker for alpha-fetoprotein-negative hepatocellular
      carcinoma.

PMID- 23533383
TI  - Probing the hepatic progenitor cell in human hepatocellular carcinoma.
AB  - Objective. The intrahepatic stem cells, also known as hepatic progenitor cells
      (HPCs), are able to differentiate into hepatocytes and bile duct epithelia. By
      exposure of different injuries and different hepatocarcinogenic regimens, the
      mature hepatocytes can no longer effectively regenerate; stem cells are involved
      in the pathogenesis of hepatocellular carcinoma. Methods. Immunohistochemistry
      was performed on 107 paraffin-embedded hepatocellular carcinoma specimens with
      the marker of hepatocyte and hepatocellular carcinoma (HepPar1), biliary
      differentiation (CK7,CK19), haemopoietic stem cell (HSC) (c-kit/CD117, CD34, and
      Thy-1/CD90), HPC specific markers (OV-6), and Ki-67, p53 protein. Results. HPCs
      can be identified in the tumor nodules, around the edge of tumor nodules, and in
      the portal tracts of the paracirrhosis nodules being positive in HepPar1, CK7,
      CK19, and OV-6, but they failed to immunostain with CD117, CD34, and CD90. The
      HPCs positive in Ki-67 are observed in the tumor and paracirrhosis tissues. In
      107 specimens, 40.2% (43/107) HCC tissues expressed p53 protein, lower than that
      of the HPCs around the tumor nodules (46.7%, 50/107) and much higher than that of
      the HPCs around the paracirrhosis nodules (8.41%, 9/107). Conclusion. Human
      hepatocellular carcinogenesis may be based on transformation of HPCs, not HSCs,
      through the formation of the transitional cells (hepatocyte-like cells and bile
      ductal cells).

PMID- 23533384
TI  - Incidence, mortality, and predictive factors of hepatocellular carcinoma in
      primary biliary cirrhosis.
AB  - Background. The study aims to analyze in detail the incidence, mortality using
      the standardized incidence ratio (SIR), and standardized mortality ratio (SMR) of
      hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC), because no
      large case studies have focused on the detailed statistical analysis of them in
      Asia. Methods. The study cohorts were consecutively diagnosed at Gunma University
      and its affiliated hospitals. Age- or sex-specific annual cancer incidence and
      deaths were obtained from Japanese Cancer Registry and Death Registry as a
      reference for the comparison of SIR or SMR of HCC. Moreover, univariate analyses
      and multivariate analyses were performed to clarify predictive factors for the
      incidence of HCC. Results. The overall 179 patients were followed up for a median
      of 97 months. HCC had developed in 13 cases. SIR for HCC was 11.6 (95% confidence
      interval (CI), 6.2-19.8) and SMR for HCC was 11.2 (95% CI, 5.4-20.6) in overall
      patients. The serum albumin levels were a predictive factor for the incidence of
      HCC in overall patients. Conclusions. The incidence and mortality of HCC in PBC
      patients were significantly higher than those in Japanese general population. PBC
      patients with low serum albumin levels were populations at high risk for HCC.

PMID- 23533385
TI  - Serum prohepcidin levels are lower in patients with atrophic gastritis.
AB  - Background/Aim. Hepcidin, an iron regulatory hormone, is increased in response to
      inflammation and some infections. We investigated the relationships among serum
      prohepcidin, iron status, Helicobacter pylori infection status, and the presence
      of gastric mucosal atrophy. Methods. Seventy subjects undergoing
      esophagogastroduodenoscopy underwent multiple gastric biopsies, and the
      possibility of H. pylori infection and the degree of endoscopic and histologic
      gastritis were investigated. In all subjects, serum prohepcidin and iron
      parameters were evaluated. Results. No correlations were observed between serum
      prohepcidin levels and the other markers of anemia, such as hemoglobin, serum
      iron, ferritin, and total iron binding capacity. Serum prohepcidin levels were
      not significantly different between the H. pylori-positive group and the H.
      pylori-negative group. Serum prohepcidin levels in atrophic gastritis patients
      were significantly lower than those in subjects without atrophic gastritis
      irrespective of H. pylori infection. Conclusion. Serum prohepcidin levels were
      not altered by H. pylori infection. Serum prohepcidin levels decrease in patients
      with atrophic gastritis, irrespective of H. pylori infection. It suggests that
      hepcidin may decrease due to gastric atrophy, a condition that causes a loss of
      hepcidin-producing parietal cells. Further investigations with a larger number of
      patients are necessary to substantiate this point.

PMID- 23533386
TI  - Glossopharyngeal Nerve Block versus Lidocaine Spray to Improve Tolerance in Upper
      Gastrointestinal Endoscopy.
AB  - Aim of the Study. To compare the effect of glossopharyngeal nerve block with
      topical anesthesia on the tolerance of patients to upper gastrointestinal
      endoscopy. Methods. We performed a clinical trial in one hundred patients
      undergoing upper gastrointestinal endoscopy. Subjects were randomly assigned to
      one of the following two groups: (1) treatment with bilateral glossopharyngeal
      nerve block (GFNB) and intravenous midazolam or (2) treatment with topical
      anesthetic (TASS) and intravenous midazolam. We evaluated sedation, tolerance to
      the procedure, hemodynamic stability, and adverse symptoms. Results. We studied
      46 men and 54 women, from 17 to 78 years of age. The procedure was reported
      without discomfort in 48 patients (88%) in the GFNB group and 32 (64%) in the
      TAAS group; 6 patients (12%) in GFNB group and 18 (36%) in TAAS group reported
      the procedure as little discomfort (chi (2) = 3.95, P = 0.04). There was no
      difference in frequency of nausea (4% in both groups) and retching, 4% versus 8%
      for GFNB and TASS group, respectively (P = 0.55). Conclusions. The use of
      glossopharyngeal nerve block provides greater comfort and tolerance to the
      patient undergoing upper gastrointestinal endoscopy. It also reduces the need for
      sedation.

PMID- 23533387
TI  - Fluorescence-guided surgery and fluorescence laparoscopy for gastrointestinal
      cancers in clinically-relevant mouse models.
AB  - There are many challenges that face surgeons when attempting curative resection
      for gastrointestinal cancers. The ability to properly delineate tumor margins for
      complete resection is of utmost importance in achieving cure and giving the
      patient the best chance of prolonged survival. Targeted tumor imaging techniques
      have gained significant interest in recent years to enable better identification
      of tumor lesions to improve diagnosis and treatment of cancer from preoperative
      staging modalities to optimizing the surgeon's ability to visualize tumor margins
      at the initial operation. Using unique characteristics of the tumor to
      fluorescently label the tissue can delineate tumor margins from normal
      surrounding tissue, allowing improved precision of surgical resection. In this
      paper, different methods of fluorescently labeling native tumor are discussed as
      well as the development of fluorescence laparoscopy and the potential role for
      fluorescence-guided surgery in the treatment of gastrointestinal cancers.

PMID- 23533388
TI  - The Diagnostic Significance of Coapplying a Rabeprazole Test with the SF-36 for
      Gastroesophageal Reflux Disease.
AB  - Gastroesophageal reflux disease is a diversity disease that affects life quality
      of people in the world. Due to the complicated pathogenesis and variations in
      clinical manifestations, there is still no true gold standard for GERD diagnosis,
      and it is still difficult to diagnose this disease in some patients. The proton
      pump inhibitor's diagnostic test (the PPI test) is noninvasive, of low cost, tied
      to treatment, and widely accepted. Our aim is to evaluate the diagnostic
      significance of coapplying a rabeprazole test with the SF-36 for GERD in this
      study. Our study shows that the SF-36 in combination with the rabeprazole test
      can screen GERD patients and increase the sensitivity and specificity of GERD
      diagnosis through reference to the change in SF-36 score before and after the
      treatment (65 in the trial).

PMID- 23533389
TI  - A pilot study to investigate the role of thymidylate synthase as a marker of
      prognosis for neoadjuvant chemotherapy in gastric and gastro-oesophageal junction
      adenocarcinoma.
AB  - Aims and Background. Patients in the United Kingdom with operable gastric and
      gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy. Our
      aim was to study the expression of thymidylate synthase (TS) enzyme in pre
      treatment diagnostic biopsy specimens and investigate its clinical usefulness.
      Methods. A single-centre study was carried out in 45 patients with gastric and
      GOJ adenocarcinoma treated with neo-adjuvant chemotherapy according to the MAGIC
      protocol. TS expression was determined using immunohistochemistry. >10% tumour
      nuclei expression of TS was used as cut-off for positivity. Results. Forty-one
      (91%) of the 45 tumours expressed TS. There was no association between TS
      expression and lymph node status (P = 0.80), histological response (P = 0.30),
      and recurrence (P = 0.55). On univariate analysis, only N-stage (P = 0.02) and
      vascular invasion (P = 0.04) were associated with a poor prognosis. Patients with
      negative tumour TS expression had better outcome than those with positive
      expression. The overall 5-year survival rate was 100% in the TS negative versus
      56% in TS positive group, but the difference was not statistically significant (P
      = 0.17). Conclusion. TS expression should be studied in a larger series of gastro
      oesophageal cancers as a potential prognostic marker of prognosis to neo-adjuvant
      chemotherapy.

PMID- 23533390
TI  - Combined EUS-Guided Abdominal Cavity Drainage and Cystogastrostomy for the
      Ruptured Pancreatic Pseudocyst.
AB  - Background. Endoscopic-Ultrasonography- (EUS-) guided puncture and drainage of
      pancreatic pseudocyst is currently one of the most widely accepted nonsurgical
      treatments. To date, this technique has only been used for pancreatic pseudocysts
      adhesive to the gastric wall. This study introduces the technique of EUS-guided
      pseudocyst drainage and additional EUS-guided peritoneal drainage for the
      ruptured pseudocyst. Methods. Transmural puncture and drainage of the cyst were
      performed with a 19 G needle, cystotome, and 10 Fr endoprosthesis.
      Intraperitoneal drainage was performed with a nasobiliary catheter when rupture
      of pseudocyst occurred. The entire procedure was guided by the echoendoscope.
      Results. A total of 21 patients, 8 men and 13 women, with a mean age of 36 years,
      were included in this prospective study. All of the pseudocysts were successfully
      drained by EUS. Peritoneal drainage was uneventfully performed in 4 patients.
      There were no severe complications. Complete pseudocyst resolution was
      established in all patients. Conclusion. The technique of EUS-guided transmural
      puncture and drainage, when combined with abdominal cavity drainage by a
      nasobiliary catheter, allows successful endoscopic management of pancreatic
      pseudocysts without adherence to gastric wall.

PMID- 23533391
TI  - Endoscopic submucosal dissection for early colorectal neoplasms: clinical
      experience in a tertiary medical center in taiwan.
AB  - Objectives. Endoscopic submucosal dissection (ESD) is a promising technique to
      treat early colorectal neoplasms by facilitating en bloc resection without size
      limitations. Although ESD for early gastrointestinal epithelial neoplasms has
      been popular in Japan, clinical experience with colorectal ESD has been rarely
      reported in Taiwan. Methods. From March 2006 to December 2011, 92 consecutive
      patients with early colorectal neoplasms resected by ESD at Tri-Service General
      Hospital were included. ESD was performed for colorectal epithelial neoplasms
      with a noninvasive pit pattern which had the following criteria: (1) lesions
      difficult to remove en bloc with a snare, such as laterally spreading tumors
      nongranular type (LST-NG) ?20 mm and laterally spreading tumors-granular type
      (LST-G) ?30 mm; (2) lesions with fibrosis or which had recurred after endoscopic
      mucosal resection with a nonlifting sign. Results. The mean age of the patients
      was 66.3 +/- 12.9 years, and the male-female ratio was 1.8 : 1. The mean tumor
      size was 37.2 +/- 17.9 mm. The en bloc resection rate was 90.2% and the R0
      resection rate was 89.1%. Perforations during ESD occurred in 11 patients (12.0%)
      and all of them were effectively treated by endoscopic closure with hemoclips. No
      delayed perforation or postoperative bleeding was recorded. There were no
      procedure-related morbidities or mortalities. Conclusion. ESD is an effective
      method for en bloc resection of large early colorectal neoplasms and those with a
      nonlifting sign. An endoscopic technique to close perforations is essential for
      colorectal ESD.

PMID- 23533392
TI  - Model construction for the intention to use telecare in patients with chronic
      diseases.
AB  - Objective. This study chose patients with chronic diseases as study subjects to
      investigate their intention to use telecare. Methods. A large medical institute
      in Taiwan was used as the sample unit. Patients older than 20 years, who had
      chronic diseases, were sampled by convenience sampling and surveyed with a
      structural questionnaire, and a total of 500 valid questionnaires were collected.
      Model construction was based on the Health Belief Model. The reliability and
      validity of the measurement model were tested using confirmatory factor analysis
      (CFA), and the causal model was explained by structural equation modeling (SEM).
      Results. The priority should be on promoting the perceived benefits of telecare,
      with a secondary focus on the external cues to action, such as promoting the
      influences of important people on the patients. Conclusion. The findings
      demonstrated that patients with chronic diseases use telecare differently from
      the general public. To promote the use and acceptance of telecare in patients
      with chronic diseases, technology developers should prioritize the promotion of
      the usefulness of telecare. In addition, policy makers can strengthen the
      marketing from media and medical personnel, in order to increase the acceptance
      of telecare by patients with chronic diseases.

PMID- 23533393
TI  - Anesthesia with Propofol versus Sevoflurane: Does the Longer Neuromuscular Block
      under Sevoflurane Anesthesia Reduce Laryngeal Injuries?
AB  - Anesthesia can be maintained with propofol or sevoflurane. Volatile anesthetics
      increase neuromuscular block of muscle relaxants. We tested the hypothesis, that
      sevoflurane would cause less vocal cord injuries than an intravenous anesthesia
      with propofol. In this prospective trial, 65 patients were randomized in 2
      groups: SEVO group, anesthesia with sevoflurane, and TIVA group, total
      intravenous anesthesia with propofol. Intubating and extubating conditions were
      evaluated. Vocal cord injuries were examined by stroboscopy before and 24 and 72
      h after surgery; hoarseness and sore throat were assessed up to 72 h after
      surgery. Hoarseness and sore throat were comparable between both groups (not
      significant). Similar findings were observed for vocal cord injuries: 9 (SEVO)
      versus 5 (TIVA) patients; P = 0.36; the overall incidence was 24%. Type of vocal
      cord injuries: 9 erythema and 5 edema of the vocal folds. Neuromuscular block was
      significantly longer in the SEVO group compared with the TIVA group: 71 (range:
      38-148) min versus 52 (range: 21-74) min; P < 0.001. Five patients (TIVA group)
      versus 11 patients (SEVO group) needed neostigmine to achieve a TOF ratio of 1.0
      (P = 0.14). Under anesthesia with propofol laryngeal injuries were not increased;
      the risk for residual curarization, however, was lower compared with sevoflurane.

PMID- 23533394
TI  - Unexplained Falls Are Frequent in Patients with Fall-Related Injury Admitted to
      Orthopaedic Wards: The UFO Study (Unexplained Falls in Older Patients).
AB  - To evaluate the incidence of unexplained falls in elderly patients affected by
      fall-related fractures admitted to orthopaedic wards, we recruited 246
      consecutive patients older than 65 (mean age 82 +/- 7 years, range 65-101). Falls
      were defined "accidental" (fall explained by a definite accidental cause),
      "medical" (fall caused directly by a specific medical disease), "dementia
      related" (fall in patients affected by moderate-severe dementia), and
      "unexplained" (nonaccidental falls, not related to a clear medical or drug
      induced cause or with no apparent cause). According to the anamnestic features of
      the event, older patients had a lower tendency to remember the fall. Patients
      with accidental fall remember more often the event. Unexplained falls were
      frequent in both groups of age. Accidental falls were more frequent in younger
      patients, while dementia-related falls were more common in the older ones.
      Patients with unexplained falls showed a higher number of depressive symptoms. In
      a multivariate analysis a higher GDS and syncopal spells were independent
      predictors of unexplained falls. In conclusion, more than one third of all falls
      in patients hospitalized in orthopaedic wards were unexplained, particularly in
      patients with depressive symptoms and syncopal spells. The identification of fall
      causes must be evaluated in older patients with a fall-related injury.

PMID- 23533396
TI  - Changing Behavior among Nurses to Track Indwelling Urinary Catheters in
      Hospitalized Patients.
AB  - Catheter-associated urinary tract infections (CAUTIs) are preventable
      complications of hospitalization. An interdisciplinary team developed a
      curriculum to increase awareness of the presence of indwelling urinary catheters
      (IUCs) in hospitalized patients, addressed practical, primarily nurse-controlled
      inpatient risk-reduction interventions, and promoted the use of the IUC labels
      ("tags"). Five thirty-minute educational sessions were cycled over three daily
      nursing shifts on two inpatient medical floors over a 1-year period; participants
      were surveyed (n = 152) to elicit feedback and provide real-time insight on the
      learning objectives. Nurse self-reported IUC tagging was early and sustained;
      after the IUC tag was introduced, there was a significant increase in tagging
      reported by the end of the block of educational sessions (from 46.2% to 84.6%, P
      = 0.001). Early engagement combined with a targeted educational initiative led to
      increased knowledge, changes in behavior, and renewed CAUTI awareness in
      hospitalized patients with IUCs. The processes employed in this small-scale
      project can be applied to broader, hospitalwide initiatives and to large-scale
      initiatives for healthcare interventions. As first-line providers with
      responsibility for the placement and daily maintenance of IUCs, nurses are
      ideally positioned to implement efforts addressing CAUTIs in the hospital
      setting.

PMID- 23533395
TI  - Predicting delirium duration in elderly hip-surgery patients: does early symptom
      profile matter?
AB  - Background. Features that may allow early identification of patients at risk of
      prolonged delirium, and therefore of poorer outcomes, are not well understood.
      The aim of this study was to determine if preoperative delirium risk factors and
      delirium symptoms (at onset and clinical symptomatology during the course of
      delirium) are associated with delirium duration. Methods. This study was
      conducted in prospectively identified cases of incident delirium. We compared
      patients experiencing delirium of short duration (1 or 2 days) with patients who
      had more prolonged delirium (>=3 days) with regard to DRS-R-98 (Delirium Rating
      Scale Revised-98) symptoms on the first delirious day. Delirium symptom profile
      was evaluated daily during the delirium course. Results. In a homogenous
      population of 51 elderly hip-surgery patients, we found that the severity of
      individual delirium symptoms on the first day of delirium was not associated with
      duration of delirium. Preexisting cognitive decline was associated with prolonged
      delirium. Longitudinal analysis using the generalised estimating equations method
      (GEE) identified that more severe impairment of long-term memory across the whole
      delirium episode was associated with longer duration of delirium. Conclusion.
      Preexisting cognitive decline rather than severity of individual delirium
      symptoms at onset is strongly associated with delirium duration.

PMID- 23533397
TI  - Reduced dynamic models in epithelial transport.
AB  - Most models developed to represent transport across epithelia assume that the
      cell interior constitutes a homogeneous compartment, characterized by a single
      concentration value of the transported species. This conception differs
      significantly from the current view, in which the cellular compartment is
      regarded as a highly crowded media of marked structural heterogeneity. Can the
      finding of relatively simple dynamic properties of transport processes in
      epithelia be compatible with this complex structural conception of the cell
      interior? The purpose of this work is to contribute with one simple theoretical
      approach to answer this question. For this, the techniques of model reduction are
      utilized to obtain a two-state reduced model from more complex linear models of
      transcellular transport with a larger number of intermediate states. In these
      complex models, each state corresponds to the solute concentration in an
      intermediate intracellular compartment. In addition, the numerical studies reveal
      that it is possible to approximate a general two-state model under conditions
      where strict reduction of the complex models cannot be performed. These results
      contribute with arguments to reconcile the current conception of the cell
      interior as a highly complex medium with the finding of relatively simple dynamic
      properties of transport across epithelial cells.

PMID- 23533398
TI  - Potassium Current Is Not Affected by Long-Term Exposure to Ghrelin or GHRP-6 in
      Somatotropes GC Cells.
AB  - Ghrelin is a growth hormone (GH) secretagogue (GHS) and GHRP-6 is a synthetic
      peptide analogue; both act through the GHS receptor. GH secretion depends
      directly on the intracellular concentration of Ca(2+); this is determined from
      the intracellular reserves and by the entrance of Ca(2+) through the voltage
      dependent calcium channels, which are activated by the membrane depolarization.
      Membrane potential is mainly determined by K(+) channels. In the present work, we
      investigated the effect of ghrelin (10 nM) or GHRP-6 (100 nM) for 96 h on
      functional expression of voltage-dependent K(+) channels in rat somatotropes: GC
      cell line. Physiological patch-clamp whole-cell recording was used to register
      the K(+) currents. With Cd(2+) (1 mM) and tetrodotoxin (1  MU m) in the bath
      solution recording, three types of currents were characterized on the basis of
      their biophysical and pharmacological properties. GC cells showed a K(+) current
      with a transitory component (I A) sensitive to 4-aminopyridine, which represents
      ~40% of the total outgoing current; a sustained component named delayed rectifier
      (I K), sensitive to tetraethylammonium; and a third type of K(+) current was
      recorded at potentials more negative than -80 mV, permitting the entrance of K(+)
      named inward rectifier (KIR). Chronic treatment with ghrelin or GHRP-6 did not
      modify the functional expression of K(+) channels, without significant changes (P
      < 0.05) in the amplitudes of the three currents observed; in addition, there were
      no modifications in their biophysical properties and kinetic activation or
      inactivation.

PMID- 23533399
TI  - Spectral analysis on time-course expression data: detecting periodic genes using
      a real-valued iterative adaptive approach.
AB  - Time-course expression profiles and methods for spectrum analysis have been
      applied for detecting transcriptional periodicities, which are valuable patterns
      to unravel genes associated with cell cycle and circadian rhythm regulation.
      However, most of the proposed methods suffer from restrictions and large false
      positives to a certain extent. Additionally, in some experiments, arbitrarily
      irregular sampling times as well as the presence of high noise and small sample
      sizes make accurate detection a challenging task. A novel scheme for detecting
      periodicities in time-course expression data is proposed, in which a real-valued
      iterative adaptive approach (RIAA), originally proposed for signal processing, is
      applied for periodogram estimation. The inferred spectrum is then analyzed using
      Fisher's hypothesis test. With a proper p-value threshold, periodic genes can be
      detected. A periodic signal, two nonperiodic signals, and four sampling
      strategies were considered in the simulations, including both bursts and drops.
      In addition, two yeast real datasets were applied for validation. The simulations
      and real data analysis reveal that RIAA can perform competitively with the
      existing algorithms. The advantage of RIAA is manifested when the expression data
      are highly irregularly sampled, and when the number of cycles covered by the
      sampling time points is very reduced.

PMID- 23533400
TI  - Identification of Robust Pathway Markers for Cancer through Rank-Based Pathway
      Activity Inference.
AB  - One important problem in translational genomics is the identification of reliable
      and reproducible markers that can be used to discriminate between different
      classes of a complex disease, such as cancer. The typical small sample setting
      makes the prediction of such markers very challenging, and various approaches
      have been proposed to address this problem. For example, it has been shown that
      pathway markers, which aggregate the gene activities in the same pathway, tend to
      be more robust than gene markers. Furthermore, the use of gene expression ranking
      has been demonstrated to be robust to batch effects and that it can lead to more
      interpretable results. In this paper, we propose an enhanced pathway activity
      inference method that uses gene ranking to predict the pathway activity in a
      probabilistic manner. The main focus of this work is on identifying robust
      pathway markers that can ultimately lead to robust classifiers with reproducible
      performance across datasets. Simulation results based on multiple breast cancer
      datasets show that the proposed inference method identifies better pathway
      markers that can predict breast cancer metastasis with higher accuracy. Moreover,
      the identified pathway markers can lead to better classifiers with more
      consistent classification performance across independent datasets.

PMID- 23533402
TI  - Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells.
AB  - Phenanthrene (Phe), a polycyclic aromatic hydrocarbon (PAH), is a major
      constituent of urban air pollution. There have been conflicting results regarding
      the role of other AhR ligands 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and 6
      formylindolo [3,2-b]carbazole (FICZ) in modifying regulatory T cell populations
      (Treg) or T helper (Th)17 differentiation, and the effects of Phe have been
      understudied. We hypothesized that different chemical entities of PAH induce Treg
      to become either Th2 or Th17 effector T cells through epigenetic modification of
      FOXP3. To determine specific effects on T cell populations by phenanthrene,
      primary human Treg were treated with Phe, TCDD, or FICZ and assessed for
      function, gene expression, and phenotype. Methylation of CpG sites within the
      FOXP3 locus reduced FOXP3 expression, leading to impaired Treg function and
      conversion of Treg into a CD4(+)CD25(lo) Th2 phenotype in Phe-treated cells.
      Conversely, TCDD treatment led to epigenetic modification of IL-17A and
      conversion of Treg to Th17 T cells. These findings present a mechanism by which
      exposure to AhR-ligands mediates human T cell responses and begins to elucidate
      the relationship between environmental exposures, immune modulation, and
      initiation of human disease.

PMID- 23533403
TI  - Establishing reference intervals for bone turnover markers in the healthy
      shanghai population and the relationship with bone mineral density in
      postmenopausal women.
AB  - The reference ranges of bone turnover markers (BTMs) were important during the
      treatment of osteoporosis, and the associations with bone mineral density (BMD)
      were controversial. The aim of this study was to establish the reference ranges
      of N-terminal procollagen of type l collagen (P1NP), osteocalcin (OC), and beta C
      terminal cross-linked telopeptides of type I collagen ( beta -CTX) in Shanghai
      area and to investigate the relationships between BTMs and BMD in postmenopausal
      women. 2,799 subjects recruited in Shanghai City were measured BTMs to establish
      the reference ranges. Additional 520 healthy postmenopausal women were also
      measured BTMs, these women measured BMD in addition. BTMs were measured using the
      Roche electrochemiluminescence system. We used the age range of 35 to 45-year
      olds to calculate reference intervals. The reference range of OC was 4.91 to
      13.90 ng/mL for women and 5.58 to 16.57 ng/mL for men, P1NP was 13.72 to 32.90
      ng/mL for women and 16.89 to 42.43 ng/mL for men, and beta -CTX was 0.112 to
      0.210 ng/mL for women and 0.100 to 0.378 ng/mL for men. BTMs significantly
      negatively correlated with lumbar spine and femoral and total hip in
      postmenopausal women (Betastd = -0.157 ~ -0.217, P < 0.001). We established the
      normal reference ranges of P1NP, OC, and beta -CTX in the Shanghai area. This
      study also found that BTMs correlated with BMD and suggested that BTMs were the
      key determining factors of early BMD decreases.

PMID- 23533401
TI  - A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from
      Exposure to 2,4-D and MCPA in the Environment.
AB  - Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and
      4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used
      herbicides in the United States for both agricultural and residential
      applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may
      be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin's disease
      (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents
      show no evidence of carcinogenicity, and regulatory agencies worldwide consider
      chlorophenoxies as not likely to be carcinogenic or unclassifiable as to
      carcinogenicity. This systematic review assembles the available data to evaluate
      epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring
      studies with respect to key cellular events noted in disease etiology and how
      those relate to hypothesized modes of action for these constituents to determine
      the plausibility of an association between exposure to environmentally relevant
      concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined
      evidence does not support a genotoxic mode of action. Although plausible
      hypotheses for other carcinogenic modes of action exist, a comparison of
      biomonitoring data to oral equivalent doses calculated from bioassay data shows
      that environmental exposures are not sufficient to support a causal relationship.
      Genetic polymorphisms exist that are known to increase the risk of developing
      NHL. The potential interaction between these polymorphisms and exposures to
      chlorophenoxy compounds, particularly in occupational settings, is largely
      unknown.

PMID- 23533404
TI  - Effects of low-dose testosterone undecanoate treatment on bone mineral density
      and bone turnover markers in elderly male osteoporosis with low serum
      testosterone.
AB  - This prospective 2-year, single-center, randomized, placebo-controlled, open
      label clinical trial was performed to evaluate the efficacy of low-dose
      testosterone undecanoate (TU) treatment on bone mineral density (BMD) and
      biochemical markers of bone turnover in elderly male osteoporosis with low serum
      testosterone. A total of 186 elderly male osteoporosis patients with low serum
      testosterone were randomized into three groups: low-dose TU (20 mg, per day),
      standard-dose TU (40 mg, per day), and placebo group with a 24-month followup.
      Since the 6th month in standard-dose TU group or since the 12th month followup in
      low-dose TU group and throughout the study, lumbar spine and femoral neck BMD and
      serum levels of free testosterone, estradiol, and bone alkaline phosphatase
      significantly increased. There were no significant differences between groups of
      low-dose TU and standard dose TU in the percentage of changes of these data since
      the 18th month followup and throughout the study. No side effects on prostate
      glands including prostate specific antigen were found. In conclusion, low-dose TU
      (20 mg, per day) may be a cost effective and safe protocol for treating elderly
      male osteoporosis with low serum testosterone.

PMID- 23533405
TI  - Twenty years of experience with the preoperative diagnosis of medullary cancer in
      a moderately iodine-deficient region.
AB  - Background. There is a current debate in the medical literature about plasma
      calcitonin screening in patients with nodular goiter (NG). We decided on
      analyzing our 20-year experience with patients in an iodine-deficient region
      (ID). Patients and Methods. 22,857 consecutive patients with NG underwent
      ultrasonography and aspiration cytology (FNAC). If FNAC raised suspicion of
      medullary cancer (MTC), the serum calcitonin was measured. Results. 4,601
      patients underwent surgery; there were 23 patients among them who had MTC (0.1%
      prevalence). Significantly more MTC cases were diagnosed cytologically in the
      second decade than in the first: 11/12 and 6/11, respectively. The frozen section
      was of help in 2 cases out of 3. Two patients suffered from a 3-year delay in
      proper therapy, and reoperation was necessary in 1 case. FNAC raised the
      suspicion of MTC in 20 cases that were later histologically verified and did not
      present MTC. The diagnostic accuracy of FNAC in diagnosing MTC was 99.2%. Two
      false-positive serum calcitonin tests (one of them in a hemodialyzed patient) and
      one false-negative serum calcitonin test occurred in 40 cases. Conclusion.
      Regarding the low prevalence of MTC in ID regions, calcitonin screening of all NG
      patients does not only appear superfluously but may have more disadvantages than
      advantages.

PMID- 23533407
TI  - The Relationship between Serum Osteocalcin Concentration and Glucose Metabolism
      in Patients with Type 2 Diabetes Mellitus.
AB  - To study the correlations between serum osteocalcin and glucose metabolism in
      patients with type 2 diabetes, 66 cases were collected to determine total
      osteocalcin, undercarboxylated osteocalcin, fasting blood glucose, fasting
      insulin, and HbA1c. Osteocalcin concentrations were compared between groups of
      different levels of HbA1c, and parameters of glucose metabolism were compared
      between groups of different levels of total osteocalcin and undercarboxylated
      osteocalcin. The relationship between osteocalcin and parameters of glucose
      metabolism was also analyzed. We found that the total osteocalcin concentration
      of high-HbA1c group was significantly lower than that of low-HbA1c group. The
      fasting blood glucose of low-total-osteocalcin group was significantly higher
      than that of high-total-osteocalcin group in male participants, while the fasting
      blood glucose of low-undercarboxylated-osteocalcin group was significantly higher
      than that of high-undercarboxylated-osteocalcin group in all participants and in
      male participants. Total osteocalcin was inversely correlated with HbA1c, and
      undercarboxylated osteocalcin was inversely correlated with fasting blood
      glucose. However, no significant correlation was found between osteocalcin and
      HOMA-IR. Total osteocalcin was an independent related factor of HbA1c level. In
      summary, decreased serum total osteocalcin and undercarboxylated osteocalcin are
      closely related to the exacerbation of glucose metabolism disorder but have no
      relations with insulin resistance.

PMID- 23533408
TI  - Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small
      Cell Lung Cancer.
AB  - Background. A significant number of non-small-cell lung cancers (NSCLC) have
      human papillomavirus (HPV) DNA integrated in their genome. This study sought to
      further establish HPV's possible etiologic link to NSCLC by evaluating an immune
      response to HPV's oncogene, E7, in patients with NSCLC. Patients and Methods.
      Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC
      were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen
      NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7
      protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas
      (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher
      frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2
      SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC,
      and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high
      cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who
      reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were
      HPV positive. Conclusions. The study detected high levels of IgG against E7 in
      16% of NSCLC patients. This adds evidence to a potential role of HPV in the
      pathogenesis of NSCLC.

PMID- 23533409
TI  - Prevalence of human papillomavirus in 45 greek patients with oral cancer.
AB  - The relation between HPV and head and neck cancer has recently and extensively
      been investigated. The purpose of this study was to indentify HPV genotypes, as
      well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33 and 45) in oral
      squamous cell carcinomas (OSCCs) from 45 Greek patients. The overall prevalence
      of HPV DNA positive OSCCs was 11.1% (5/45), while high-risk HPV DNA was found in
      6.7% (3/45) of OSCCs. E6/E7 mRNA expression was detected in 8.9% (4/45) of the
      oral cavity samples. Our data indicated that HPV 16 was the commonest genotype
      identified in HPV-positive OSCCs by both DNA and RNA tests. This study confirms
      the prevalence of HPV infections among patients with OSCCs. Future analysis and
      followup of more OSCCs will enable us to correlate HPV detection and clinical
      outcome.

PMID- 23533410
TI  - Mammalian target of rapamycin inhibitors induce tumor cell apoptosis in vivo
      primarily by inhibiting VEGF expression and angiogenesis.
AB  - We found that rapalog mTOR inhibitors induce G1 arrest in the PTEN-null HS Sultan
      B-cell lymphoma line in vitro, but that administration of rapalogs in a HS Sultan
      xenograft model resulted in significant apoptosis, and that this correlated with
      induction of hypoxia and inhibition of neoangiogenesis and VEGF expression.
      Mechanistically, rapalogs prevent cap-dependent translation, but studies have
      shown that cap-independent, internal ribosome entry site (IRES)-mediated
      translation of genes, such as c-myc and cyclin D, can provide a fail-safe
      mechanism that regulates tumor survival. Therefore, we tested if IRES-dependent
      expression of VEGF could likewise regulate sensitivity of tumor cells in vivo. To
      achieve this, we developed isogenic HS Sultan cell lines that ectopically express
      the VEGF ORF fused to the p27 IRES, an IRES sequence that is insensitive to AKT
      mediated inhibition of IRES activity and effective in PTEN-null tumors. Mice
      challenged with p27-VEGF transfected tumor cells were more resistant to the
      antiangiogenic and apoptotic effects of the rapalog, temsirolimus, and active
      site mTOR inhibitor, pp242. Our results confirm the critical role of VEGF
      expression in tumors during treatment with mTOR inhibitors and underscore the
      importance of IRES activity as a resistance mechanism to such targeted therapy.

PMID- 23533406
TI  - Small-molecule hormones: molecular mechanisms of action.
AB  - Small-molecule hormones play crucial roles in the development and in the
      maintenance of an adult mammalian organism. On the molecular level, they regulate
      a plethora of biological pathways. Part of their actions depends on their
      transcription-regulating properties, exerted by highly specific nuclear receptors
      which are hormone-dependent transcription factors. Nuclear hormone receptors
      interact with coactivators, corepressors, basal transcription factors, and other
      transcription factors in order to modulate the activity of target genes in a
      manner that is dependent on tissue, age and developmental and pathophysiological
      states. The biological effect of this mechanism becomes apparent not earlier than
      30-60 minutes after hormonal stimulus. In addition, small-molecule hormones
      modify the function of the cell by a number of nongenomic mechanisms, involving
      interaction with proteins localized in the plasma membrane, in the cytoplasm, as
      well as with proteins localized in other cellular membranes and in nonnuclear
      cellular compartments. The identity of such proteins is still under
      investigation; however, it seems that extranuclear fractions of nuclear hormone
      receptors commonly serve this function. A direct interaction of small-molecule
      hormones with membrane phospholipids and with mRNA is also postulated. In these
      mechanisms, the reaction to hormonal stimulus appears within seconds or minutes.

PMID- 23533411
TI  - Epidemiology of thyroid cancer in an area of epidemic thyroid goiter.
AB  - The aim of this study was to analyze and describe the epidemiological
      characteristics and trends of thyroid cancer in the province of Sassari
      (Sardinia, Italy), an area with epidemic thyroid goiter, in the period 1992-2010.
      Data were obtained from the local tumor registry which makes part of a wider
      registry web, coordinated today by the Italian Association for Tumor Registries.
      An increasing trend in the incidence of thyroid cancer in the province of Sassari
      was evidenced. This trend seems to follow the general worldwide trend and does
      not seem to be related to the high incidence of thyroid goiter in the area. The
      frequencies of the different histological subtypes were similar to those reported
      in numerous national and international reports. Women are affected earlier than
      men and, therefore, suffer greater professional, economic, and social impacts.
      Overall mortality is low and a relative 5-year survival is excellent, especially
      in comparison to other malignancies.

PMID- 23533412
TI  - Clinical and Radiographic Evaluation of Branemark Implants with an Anodized
      Surface following Seven-to-Eight Years of Functional Loading.
AB  - The aim of this study was to evaluate the clinical and radiographic long-term
      outcomes of dental implants with an anodized TiUnite surface, placed in routine
      clinical practice. Two clinical centers participated in the study. One hundred
      and seven implants (80 in the maxilla and 27 in the mandible) in 52 patients were
      followed in the long term. Both one- and two-stage techniques were used for 38
      and 69 implants, respectively. Thirty-eight single tooth restorations and 22
      fixed partial prostheses were delivered, according to a delayed loading protocol,
      within 4 to 12 months since implant placement. All implants were stable at
      insertion and at the long-term follow-up visit, which occurred between 7 and 8
      years of functional loading. The mean followup was 7.33 +/- 0.47 years. The mean
      marginal bone level change at the long-term followup as compared to baseline was
      1.49 +/- 1.03 mm. No implant failure occurred. Healthy peri-implant mucosa was
      found around 95% of implants, whereas 91% of implants showed no visible plaque at
      the implant surfaces at the long-term followup. The study showed that dental
      implants with the TiUnite anodized surface demonstrate excellent long-term
      clinical and radiographic outcomes.

PMID- 23533413
TI  - Mixed red-complex bacterial infection in periodontitis.
AB  - The red complex, which includes Porphyromonas gingivalis, Treponema denticola,
      and Tannerella forsythia (formerly Bacteroides forsythus), are recognized as the
      most important pathogens in adult periodontal disease. These bacteria are usually
      found together in periodontal pockets, suggesting that they may cause destruction
      of the periodontal tissue in a cooperative manner. This article discusses the
      interspecies pathogenic interactions within the red complex.

PMID- 23533414
TI  - Factors related to oral health-related quality of life of independent brazilian
      elderly.
AB  - The aim of this cross-sectional study was to assess the factors associated with
      the impact of oral health on the quality of life in a sample of 504 Brazilian
      independent elderly. Data collection included oral examinations and structured
      interviews. The simplified form of the Oral Health Impact Profile (OHIP-14) was
      used to measure OHRQoL. Information on sociodemographic characteristics, use of
      dental services, and subjective measures of health was collected. Poisson
      regression within a hierarchical model was used to data analyses. The following
      variables were associated with a negative impact on OHRQoL: female gender (PR =
      1.40; CI 95%: 1.11-1.77); lower class (PR = 1.58; CI 95%: 1.13-2.20); up to 3
      occluding pairs of posterior teeth (PR = 1.88; CI 95%: 1.13-3.14); at least one
      untreated caries (PR = 1.28; CI 95%: 1.06-1.54); curative reasons for the last
      dental appointment (PR = 1.52; CI 95%: 1.15-2.00); poor self-perception of oral
      health (PR = 2.49; CI 95%: 1.92-3.24); and poor perception of dental care
      provided (PR = 1.34; CI 95%: 1.12-1.59). The younger elderly also noticed this
      negative impact. These findings showed that the clinical, sociodemographic, and
      subjective factors evaluated exerted a negative impact on OHRQoL in elderly
      people. Health authorities must address all these factors when planning
      interventions on oral health for this population.

PMID- 23533415
TI  - Three-point bending tests of zirconia core/veneer ceramics for dental
      restorations.
AB  - Introduction. The mechanical strength and the surface hardness of commercially
      available yttrium-doped zirconia were investigated. Furthermore, a comparative
      study of eight different ceramic veneers, to be used for the production of two
      layered all-ceramic restorative systems, was carried out. Materials and Methods.
      Four types of zirconia specimens were analyzed, according to a standard ISO
      procedure (ISO 6872). Besides, two-layered zirconia-veneer specimens were
      prepared for three-point bending tests. Results. A strong effect of the surface
      roughness on the mechanical strength of zirconia specimens was observed. Finally,
      a comparative study of eight commercially available veneering ceramics shows
      different modes of failure between the selected veneers. Conclusion. The results
      indicate that close attention should be paid to the preparation of zirconia-based
      crowns and bridges by CAD/CAM process, because surface roughness has an important
      effect on the mechanical strength of the material. Finally, the results of the
      mechanical tests on two-layered specimens represent an important support to the
      choice of the veneering ceramic.

PMID- 23533416
TI  - Engineering a biocompatible scaffold with either micrometre or nanometre scale
      surface topography for promoting protein adsorption and cellular response.
AB  - Surface topographical features on biomaterials, both at the submicrometre and
      nanometre scales, are known to influence the physicochemical interactions between
      biological processes involving proteins and cells. The nanometre-structured
      surface features tend to resemble the extracellular matrix, the natural
      environment in which cells live, communicate, and work together. It is believed
      that by engineering a well-defined nanometre scale surface topography, it should
      be possible to induce appropriate surface signals that can be used to manipulate
      cell function in a similar manner to the extracellular matrix. Therefore, there
      is a need to investigate, understand, and ultimately have the ability to produce
      tailor-made nanometre scale surface topographies with suitable surface chemistry
      to promote favourable biological interactions similar to those of the
      extracellular matrix. Recent advances in nanoscience and nanotechnology have
      produced many new nanomaterials and numerous manufacturing techniques that have
      the potential to significantly improve several fields such as biological sensing,
      cell culture technology, surgical implants, and medical devices. For these fields
      to progress, there is a definite need to develop a detailed understanding of the
      interaction between biological systems and fabricated surface structures at both
      the micrometre and nanometre scales.

PMID- 23533419
TI  - Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of
      Streptococcus mutans.
AB  - Cotrimoxazole inhibits dhfr and dhps and reportedly selects for drug resistance
      in pathogens. Here, Streptococcus mutans isolates were obtained from saliva of
      HIV/AIDS patients taking cotrimoxazole prophylaxis in Uganda. The isolates were
      tested for resistance to cotrimoxazole and their folP DNA (which encodes
      sulfonamide-targeted enzyme dhps) cloned in pUC19. A set of recombinant plasmids
      carrying different point mutations in cloned folP were separately transformed
      into folP-deficient Escherichia coli. Using sulfonamide-containing media, we
      assessed the growth of folP-deficient bacteria harbouring plasmids with differing
      folP point mutations. Interestingly, cloned folP with three mutations (A37V,
      N172D, R193Q) derived from Streptococcus mutans 8 conferred substantial
      resistance against sulfonamide to folP-deficient bacteria. Indeed, change of any
      of the three residues (A37V, N172D, and R193Q) in plasmid-encoded folP diminished
      the bacterial resistance to sulfonamide while removal of all three mutations
      abolished the resistance. In contrast, plasmids carrying four other mutations
      (A46V, E80K, Q122H, and S146G) in folP did not similarly confer any sulfonamide
      resistance to folP-knockout bacteria. Nevertheless, sulfonamide resistance (MIC =
      50  MU M) of folP-knockout bacteria transformed with plasmid-encoded folP was
      much less than the resistance (MIC = 4 mM) expressed by chromosomally-encoded
      folP. Therefore, folP point mutations only partially explain bacterial resistance
      to sulfonamide.

PMID- 23533420
TI  - Development of a Cell-Based Functional Assay for the Detection of Clostridium
      botulinum Neurotoxin Types A and E.
AB  - The standard procedure for definitive detection of BoNT-producing Clostridia is a
      culture method combined with neurotoxin detection using a standard mouse bioassay
      (MBA). The mouse bioassay is highly sensitive and specific, but it is expensive
      and time-consuming, and there are ethical concerns due to use of laboratory
      animals. Cell-based assays provide an alternative to the MBA in screening for
      BoNT-producing Clostridia. Here, we describe a cell-based assay utilizing a
      fluorescence reporter construct expressed in a neuronal cell model to study toxin
      activity in situ. Our data indicates that the assay can detect as little as 100
      pM BoNT/A activity within living cells, and the assay is currently being
      evaluated for the analysis of BoNT in food matrices. Among available in vitro
      assays, we believe that cell-based assays are widely applicable in high
      throughput screenings and have the potential to at least reduce and refine animal
      assays if not replace it.

PMID- 23533418
TI  - Functions of BCL-X L at the Interface between Cell Death and Metabolism.
AB  - The BCL-2 homolog BCL-XL, one of the two protein products of BCL2L1, has
      originally been characterized for its prominent prosurvival functions. Similar to
      BCL-2, BCL-XL binds to its multidomain proapoptotic counterparts BAX and BAK,
      hence preventing the formation of lethal pores in the mitochondrial outer
      membrane, as well as to multiple BH3-only proteins, thus interrupting apical
      proapoptotic signals. In addition, BCL-XL has been suggested to exert
      cytoprotective functions by sequestering a cytosolic pool of the pro-apoptotic
      transcription factor p53 and by binding to the voltage-dependent anion channel 1
      (VDAC1), thereby inhibiting the so-called mitochondrial permeability transition
      (MPT). Thus, BCL-XL appears to play a prominent role in the regulation of
      multiple distinct types of cell death, including apoptosis and regulated
      necrosis. More recently, great attention has been given to the cell death
      unrelated functions of BCL-2-like proteins. In particular, BCL-XL has been shown
      to modulate a number of pathophysiological processes, including-but not limited
      to-mitochondrial ATP synthesis, protein acetylation, autophagy and mitosis. In
      this short review article, we will discuss the functions of BCL-XL at the
      interface between cell death and metabolism.

PMID- 23533421
TI  - Clinical and pathological characteristics of organized hematoma.
AB  - Objective. To study the clinical and pathological characteristics of patients
      with organized hematoma with malignant features in maxillary sinuses. Subjects
      and Methods. This was a retrospective study of five patients who were treated
      surgically for organized hematoma. The preoperative CT and MRI findings were
      studied clinically. The expressions of CD31, CD34, and periostin in surgical
      samples were investigated by immunohistochemistry. Results. The clinical features
      of organized hematoma, such as a mass expanding from the maxillary sinus with
      bone destruction, resembled those of maxillary carcinoma. However, CT and MRI
      provided sufficient and useful information to differentiate this condition from
      malignancy. Surgical resection was the first-line treatment because of the
      presence of a firm capsule. Characteristic histopathological findings were a
      mixture of dilated vessels, hemorrhage, fibrin exudation, fibrosis,
      hyalinization, and neovascularization. The expressions of periostin, CD31, and
      CD34 were observed in organized hematoma of the maxillary sinus. Conclusion. The
      expressions of periostin, CD31, and CD34 were observed in organized hematoma of
      the maxillary sinus. Organized hematoma is characterized pathologically by a
      mixture of bleeding, dilated vessels, hemorrhage, fibrin exudation, fibrosis,
      hyalinization, and neovascularization. CT and MRI show heterogeneous findings
      reflecting a mixture of these pathological entities.

PMID- 23533417
TI  - Aggregates, crystals, gels, and amyloids: intracellular and extracellular
      phenotypes at the crossroads of immunoglobulin physicochemical property and cell
      physiology.
AB  - Recombinant immunoglobulins comprise an important class of human therapeutics.
      Although specific immunoglobulins can be purposefully raised against desired
      antigen targets by various methods, identifying an immunoglobulin clone that
      simultaneously possesses potent therapeutic activities and desirable
      manufacturing-related attributes often turns out to be challenging. The variable
      domains of individual immunoglobulins primarily define the unique antigen
      specificities and binding affinities inherent to each clone. The primary sequence
      of the variable domains also specifies the unique physicochemical properties that
      modulate various aspects of individual immunoglobulin life cycle, starting from
      the biosynthetic steps in the endoplasmic reticulum, secretory pathway
      trafficking, secretion, and the fate in the extracellular space and in the
      endosome-lysosome system. Because of the diverse repertoire of immunoglobulin
      physicochemical properties, some immunoglobulin clones' intrinsic properties may
      manifest as intriguing cellular phenotypes, unusual solution behaviors, and
      serious pathologic outcomes that are of scientific and clinical importance. To
      gain renewed insights into identifying manufacturable therapeutic antibodies,
      this paper catalogs important intracellular and extracellular phenotypes induced
      by various subsets of immunoglobulin clones occupying different niches of diverse
      physicochemical repertoire space. Both intrinsic and extrinsic factors that make
      certain immunoglobulin clones desirable or undesirable for large-scale
      manufacturing and therapeutic use are summarized.

PMID- 23533422
TI  - Communication Partners' Journey through Their Partner's Hearing Impairment.
AB  - The objective of this study was to further develop the Ida Institute model on
      communication partners' (CPs) journey through experiences of person with hearing
      impairment (PHI), based on the perspectives of CPs. Nine CPs of hearing aid users
      participated in this study, recruited through the Swansea hearing impaired
      support group. Semi-structured interviews were conducted, the data were analysed
      using qualitative thematic analysis and presented with the use of process mapping
      approach. Seven main phases were identified in the CP journey which includes: (1)
      contemplation, (2) awareness, (3) persuasion, (4) validation, (5) rehabilitation,
      (6) adaptation, and (7) resolution. The Ida Institute model (based on
      professionals' perspective) was compared with the new template developed (based
      on CPs' perspectives). The results suggest some commonalities and differences
      between the views of professionals and CPs. A new phase, adaptation, was
      identified from CPs reported experiences, which was not identified by
      professionals in the Ida Institute model. The CP's journey model could be a
      useful tool during audiological enablement/rehabilitation sessions to promote
      discussion between the PHI and the CP. In addition, it can be used in the
      training of hearing healthcare professionals.

PMID- 23533423
TI  - Validation of a prediction rule for the diagnosis of rheumatoid arthritis in
      patients with recent onset undifferentiated arthritis.
AB  - Objectives. To validate van der Helm-van Mil score (vHvM) and new ACR/EULAR
      criteria for the diagnosis of rheumatoid arthritis (RA) in patients with
      undifferentiated arthritis (UA). Patients and Methods. Adult patients with UA
      (swelling >=2 joints of less than 6 months duration, without diagnosis, and never
      treated with disease modifying drugs). Results. Ninety-one patients were
      included. Mean age: 55.6 years (SD: 17.4), 74% females. Median symptoms duration
      was 2 months (IR: 1-4 months). Mean van der Helm-van Mil score was 6.9 (SD: 2).
      After a mean followup of 6.2 months (SD: 6), 40.7% patients fulfilled ACR 1987 RA
      classification criteria, 28.6% fulfilled other diagnostic criteria, and 31%
      remained as UA. Receiver operator characteristic curve's (ROC's) area under the
      curve (AUC) for the vHvM score for diagnosis of RA was 0.83. A cutoff value of
      6.94 showed sensitivity of 81% and 79.7% specificity. For the new ACR/EULAR
      criteria, the ROC AUC was 0.93, and a value equal to or greater than 6 showed
      86.5% sensitivity and 87% specificity. Conclusion. van der Helm-van Mil
      prediction score and the new ACR/EULAR criteria proved to be valuable for the
      diagnosis of RA in patients with early UA.

PMID- 23533424
TI  - Ulcerative cutaneous lesions synchronously present with the diagnosis of primary
      lung cancer.
AB  - The percentage of patients with lung cancer that develop skin metastases is low.
      The diagnosis is usually made using clinical information and skin biopsy in
      patients with suspicious skin lesions and history of smoking or lung cancer. The
      prognosis for patients having lung cancer with skin metastasis is very poor. We
      describe findings in a 70-year-old man with lung cancer with skin metastases.
      Interestingly, multiple skin lesions were the first manifestation of the
      underlying lung cancer. The prognosis for patients having lung cancer with skin
      metastasis is thus very poor.

PMID- 23533425
TI  - Osteoid osteoma of the distal humerus mimicking sequela of pediatric
      supracondylar fracture: arthroscopic resection-case report and a literature
      review.
AB  - Osteoid osteoma (OO) is a small and painful benign osteoblastic tumour located
      preferentially in the shaft of long bones near the metaphyseal junctions, with a
      predilection for the lower limbs. Juxta- and intra-articular OOs are rare and
      even though hip, elbow, and talus are the most commonly reported locations, they
      may be found in any joint accounting for approximately 13% of all osteoid
      osteomas. There is usually a significant time delay between symptom initiation
      and diagnosis when the lesion is present in an uncommon location due to the
      diagnostic challenge it presents due to the lack of classical clinical signs
      and/or radiographic features found in the extra-articular lesions. A case of a
      distal humerus OO of a 15-year-old girl is presented to point out that a
      confounding factor, such as a previous paediatric supracondylar fracture, may
      further delay the already difficult diagnosis of a juxta- or intra-articular
      osteoid osteoma and also to emphasize the possibility of arthroscopic treatment
      of such lesions.

PMID- 23533426
TI  - Misdiagnosis and mistreatment of post-kala-azar dermal leishmaniasis.
AB  - Post-kala-azar dermal leishmaniasis (PKDL) is a known complication of visceral
      leishmaniasis (VL) caused by L. donovani. It is rare in VL caused by L. infantum
      and L. chagasi. In Sudan, it occurs with a frequency of 58% among successfully
      treated VL patients. In the majority of cases, PKDL can be diagnosed on the basis
      of clinical appearance, distribution of the lesions, and past history of treated
      VL. The ideal diagnostic method is to demonstrate the parasite in smears, by
      culture or PCR. Diagnosis is particularly difficult in patients who develop PKDL
      in the absence of previous history of visceral leishmaniasis. We describe a case
      of cutaneous leishmaniasis misdiagnosed as PKDL and 3 cases of PKDL who were
      either misdiagnosed or mistreated as other dermatoses. This caused exacerbation
      of their disease leading to high parasite loads in the lesions and dissemination
      to internal organs in one of the patients, who was also diabetic. The latter
      patient had L. major infection. A fourth patient with papulonodular lesions on
      the face and arms of 17-year duration and who was misdiagnosed as having PKDL is
      also described. He turned out to have cutaneous leishmaniasis due to L. major.
      Fortunately, he was not treated with steroids. He was cured with intravenous
      sodium stibogluconate.

PMID- 23533427
TI  - False Positive 18F-FDG Uptake in Mediastinal Lymph Nodes Detected with Positron
      Emission Tomography in Breast Cancer: A Case Report.
AB  - Breast cancer is the most frequently diagnosed cancer among females. It is
      accepted that lymph node involvement with metastatic tumor and the presence of
      distant metastasis are the most important prognostic factors. Accurate staging is
      important in determining prognosis and appropriate treatment. Positron emission
      tomography with computed tomography detects malignancies using 2-[18F]-fluoro-2
      deoxy-d-glucose (18F-FDG PET CT) with high accuracy and they contribute to
      decisions regarding diagnosis, staging, recurrence, and treatment response. Here,
      we report a case of false positive metastatic mediastinal lymph nodes that were
      diagnosed by 18F-FDG PET CT in a 40-year-old breast cancer patient who had
      undergone preoperative evaluation. Right paratracheal, prevascular,
      aorticopulmonary, precarinal, subcarinal, hilar, and subhilar multiple
      conglomerated mediastinal lymph nodes were revealed in addition to left breast
      mass and axillary lymph nodes. Mediastinoscopy was performed with biopsy and
      pathology was reported as granulomatous lymphadenitis. In conclusion, any
      abnormal FDG accumulation in unusual lymph nodes must be evaluated carefully and
      confirmed histopathologically.

PMID- 23533428
TI  - Lung metastasis from perineal leiomyosarcoma: a case report and a review of the
      Japanese literature.
AB  - Pulmonary metastasis from leiomyosarcoma is rare and its clinical management is
      challenging. A single lung metastasis from a perineal leiomyosarcoma occurred in
      a 79-year-old woman. Five months after resection of the lung metastasis, a new
      metastatic tumor developed in the contralateral lung. Since the patient did not
      desire to receive hospitalized treatment, TS-1 (an oral agent consisting of a
      combination of tegafur, gimeracil, and oteracil potassium) therapy was started on
      an outpatient basis. The lung metastasis has been successfully controlled for at
      least 17 months with excellent tolerability. The clinical features and the
      treatment of this case are discussed.

PMID- 23533429
TI  - Steroid cell tumor of the ovary in an adolescent: a rare case report.
AB  - Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors,
      account for less than 0.1% of all ovarian tumors, and also will present at any
      age. These tumors can produce steroids, especially testosterone, and may give
      symptoms like hirsutism, hair loss, amenorrhea, or oligomenorrhea. For the
      evaluation of androgen excess, testosterone and dehydroepiandrosterone sulfate
      (DHEA-S) are the first laboratory tests to be measured. A pelvic ultrasound and a
      magnetic resonance imaging are useful radiologic imaging techniques. Although
      steroid cell tumors are generally benign, there is a risk of malignant
      transformation and clinical malignant formation. Surgery is the most important
      and hallmark treatment.

PMID- 23533430
TI  - Nonunion with breakage of gamma nail and subsequent fracture in the ipsilateral
      femur.
AB  - We describe a rare case with breakage of gamma nail accompanied by nonunion of
      the original fracture and a subsequent new fracture in the ipsilateral femur. A
      73-year-old woman suffered a subtrochanteric fracture of the femur, and the
      fracture was fixed with gamma nail at a previous hospital. However, fracture
      reduction was not adequately achieved and a large gap remained between the
      fracture fragments. The fracture demonstrated atrophic nonunion 10 months after
      surgery, and autologous bone grafting was performed at the same hospital. Two
      months after the second surgery, a breakage of the nail at the distal screw hole
      was observed. Twenty-six months after the second surgery, the patient fell and a
      fracture occurred at the level of the nail breakage. The atrophic nonunion site
      and fresh fracture site were very close thus demonstrating a segmental fracture.
      We exchanged the original gamma nail with a long gamma nail and performed
      autologous bone grafting at the nonunion site. Both the fresh fracture site and
      the nonunion site obtained bony union. This tragic chain of events was caused by
      inappropriate initial treatment and replacing the nail to a longer nail and
      autologous bone grafting were effective as salvage surgery.

PMID- 23533432
TI  - Postoperative cervical haematoma complicated by ipsilateral carotid thrombosis
      and aphasia after anterior cervical fusion: a case report.
AB  - Hematoma alone is the most common vascular complication reported after anterior
      cervical decompression and fusion (ACDF). We present this case to report the
      occurrence of postoperative cervical hematoma complicated by ipsilateral carotid
      thrombosis and aphasia after an uncomplicated C4-6 ACDF. This is a case of a 65
      year-old woman who underwent revision fusions of the C4-5 and C6-7 levels
      complicated by postoperative cervical hematoma and carotid thrombosis. The
      patient's history, clinical examination, imaging findings, and treatment are
      reported. The revision fusions were performed and deemed routine. Approximately
      eight hours later 200 mL of blood was evacuated from a postoperative cervical
      hematoma. The patient became unresponsive and disoriented a few hours after
      evacuating the hematoma. Computed tomography and magnetic resonance imaging of
      the brain were normal, but magnetic resonance angiography demonstrated total
      occlusion of the left carotid artery. Thrombectomy was performed and the patient
      was discharged without residual deficits. At the latest followup she is fully
      functional and asymptomatic in her neck. We suggest, after evacuating a cervical
      hematoma, an evaluation of the carotids be made with MRA or cerebral angiography,
      as this may demonstrate a clot before the patient develops symptoms.

PMID- 23533431
TI  - Successful management of heparin-induced thrombocytopenia using argatroban in a
      very old woman: a case report.
AB  - Thrombosis due to heparin-induced thrombocytopenia (HIT) is rare but has a severe
      prognosis. Its management is not always easy, particularly in old patients with
      renal insufficiency. A 95-year-old woman was hospitalized for dyspnea. Curative
      treatment with unfractionated heparin was started because pulmonary embolism was
      suspected. Disseminated intravascular coagulation was then suspected because of
      thrombocytopenia, hypoprothrombinemia, hypofibrinogenemia, and a positive ethanol
      gelation test. The first immunoassay for HIT was negative. On the 12th day of
      hospitalization, bilateral cyanosis of the toes occurred associated with recent
      deep bilateral venous and arterial thrombosis at duplex ultrasound. New
      biological tests confirmed HIT and led us to stop heparin and to start argatroban
      with a positive clinical and biological evolution. Venous and arterial thrombosis
      associated with thrombocytopenia during heparin treatment must be considered HIT
      whatever the biological test results are. Argatroban is a good alternative
      treatment in the elderly.

PMID- 23533433
TI  - Culture of the aspirated coronary thromboembulus specimen: a peculiar diagnostic
      method for infective endocarditis.
AB  - A 69-year-old man was admitted to our hospital for persistent fever, myalgias,
      articular pain, headache, and hypoaesthesia of the scalp. The clinical scenario
      was typical for giant-cell arteritis. During hospital stay, patient developed
      fugax amaurosis, stroke, and acute coronary syndrome. The definitive diagnosis of
      infective endocarditis, supported by transesophageal echocardiography, was
      confirmed only by culturing the material obtained during angiography and coronary
      thromboaspiration.

PMID- 23533434
TI  - A laparoendoscopic single-site surgery approach to mesh sacrohysteropexy.
AB  - Although laparoendoscopic single-site surgery (LESS) has spread across surgical
      disciplines, this has not been the case for the repair of uterovaginal prolapse.
      We describe the use of this technique for mesh sacrohysteropexy to correct a
      global prolapse classified as stage II on the pelvic organ prolapse
      quantification (POP-Q) system. The procedure involved intraoperative modification
      of a commercially available single incision port. At the 18 months followup, the
      patient was free of symptoms and had no objective prolapse.

PMID- 23533435
TI  - Massive scrotal edema: an unusual manifestation of obstructive sleep apnea and
      obesity-hypoventilation syndrome.
AB  - Obstructive sleep apnea (OSA) may occur in association with obesity
      hypoventilation (Pickwickian) syndrome, a disorder of ventilatory control
      affecting individuals with morbid obesity. Through the pressor effects of chronic
      hypercapnia and hypoxemia, this syndrome may result in pulmonary hypertension,
      right heart failure, and massive peripheral edema. We present a case of severe
      scrotal edema in a 36-year-old male with OSA and obesity-hypoventilation
      syndrome. A tracheostomy was performed to relieve hypoxemia and led to dramatic
      improvement of scrotal edema. No scrotal surgery was necessary. Followup at two
      months showed complete resolution of scrotal edema, improvement in mental status,
      and normalization of arterial blood gas measurements. This case demonstrates that
      OSA and obesity-hypoventilation syndrome may present with massive scrotal edema.
      Furthermore, if OSA is recognized as the cause of right heart failure, and if the
      apnea is corrected, the resultant improvement in cardiac function may allow
      reversal of massive peripheral, including scrotal, edema.

PMID- 23533436
TI  - Peripartum isolated cortical vein thrombosis in a mother with postdural puncture
      headache treated with an epidural blood patch.
AB  - A 32-year-old woman presented with low pressure headache 3 days after delivery of
      her baby. An assessment of postdural puncture headache was made. This was
      initially treated with analgesia, caffeine, and fluids for the presumed
      cerebrospinal fluid (CSF) leak. The woman was readmitted two days after her
      hospital discharge with generalised seizures. A brain scan showed features of
      intracranial hypotension, and she was treated for CSF leak using an epidural
      blood patch. Her symptoms worsened and three days later, she developed a left
      homonymous quadrantanopia. An MRI scan confirmed a right parietal haematoma with
      evidence of isolated cortical vein thrombosis (ICVT).

PMID- 23533437
TI  - A case of mucosal cancer of the stomach treated by endoscopic submucosal
      dissection after which nodal metastasis became evident.
AB  - An 82-year-old male was referred to our institution for evaluation and treatment
      of a protruding lesion in the stomach. Esophagogastroduodenoscopy (EGD) showed a
      small protruding lesion and a large superficial elevated lesion on the lesser
      curvature of the stomach (macroscopic type: 0-I and 0-IIa, resp.). CT and
      endoscopic ultrasonography (EUS) visualized a small round lymph node (LN) 11 mm
      in size near the lesser curvature, although submucosal invasion was not evident.
      These two lesions were resected en bloc by endoscopic submucosal dissection
      (ESD). Pathological examination of the resected specimen showed moderately
      differentiated tubular adenocarcinoma (tub2) and well-differentiated tubular
      adenocarcinoma (tub1), respectively, which were limited to the mucosal layer.
      Because lymphatic-vascular involvement was not detected by hematoxylin and eosin
      (HE) staining, additional gastrectomy was not performed. Two months after ESD,
      follow-up EUS and CT showed an enlarged LN. EUS-guided fine needle aspiration
      (EUS-FNA) for the LN revealed metastasis. Therefore, total gastrectomy with LN
      dissection was performed. His postoperative course was uneventful. After
      discharge, he has been followed up at the outpatient department without any sign
      of recurrence for 5 years. Histological reexamination of the ESD specimen using
      immunohistochemistry showed lymphatic invasion of cancer cells in the lamina
      propria of the 0-I lesion 13 mm in size.

PMID- 23533438
TI  - Hearing loss and kidney dysfunction: finding a unifying diagnosis.
AB  - Microscopic polyangiitis (MPA) is a systemic vasculitis that affects small
      caliber vessels, with renal and lung compromise. Diagnosis can be challenging;
      timely diagnosis and treatment are important to prevent devastating complication,
      particularly renal failure. We present a case of a patient with microscopic
      polyangiitis presented with renal and pulmonary involvements with concomitant
      sensorineural hearing loss. We provide diagnostic, therapeutic, and prognostic
      keys to microscopic polyangiitis.

PMID- 23533439
TI  - A rare cause of dyspnea: sudden rupture of aortic valsalva sinus aneurysm.
AB  - Aneurysm of the sinus of Valsalva is an uncommon cardiac abnormality; however,
      the most common complication is rupture into the right heart chambers or rarely
      towards the left chambers. A ruptured aneurysm typically leads to an aortocardiac
      shunt and progressively worsening heart failure. We report a case of a 21-year
      old male who suffered an aneurysm of the sinus of Valsalva rupture into the right
      atrium who underwent successful surgical repair.

PMID- 23533440
TI  - Comparative Evaluation of Human Mesenchymal Stem Cells of Fetal (Wharton's Jelly)
      and Adult (Adipose Tissue) Origin during Prolonged In Vitro Expansion:
      Considerations for Cytotherapy.
AB  - Mesenchymal stem cells (MSCs) are somatic cells with a dual capacity for self
      renewal and differentiation, and diverse therapeutic applicability, both
      experimentally and in the clinic. These cells can be isolated from various human
      tissues that may differ anatomically or developmentally with relative ease.
      Heterogeneity due to biological origin or in vitro manipulation is, nevertheless,
      considerable and may equate to differences in qualitative and quantitative
      characteristics which can prove crucial for successful therapeutic use. With this
      in mind, in the present study we have evaluated the proliferation kinetics and
      phenotypic characteristics of MSCs derived from two abundant sources, that is,
      fetal umbilical cord matrix (Wharton's jelly) and adult adipose tissue (termed
      WJSC and ADSC, resp.) during prolonged in vitro expansion, a process necessary
      for obtaining cell numbers sufficient for clinical application. Our results show
      that WJSC are derived with relatively high efficiency and bear a substantially
      increased proliferation capacity whilst largely sustaining the expression of
      typical immunophenotypic markers, whereas ADSC exhibit a reduced proliferation
      potential showing typical signs of senescence at an early stage. By combining
      kinetic with phenotypic data we identify culture thresholds up to which both cell
      types maintain their stem properties, and we discuss the practical implications
      of their differences.

PMID- 23533442
TI  - A review of factors influencing the banking of collected umbilical cord blood
      units.
AB  - Umbilical cord blood banking efforts have increased dramatically in the past two
      decades in response to increasing demand for alternative sources of blood stem
      cells to support patients requiring hematopoietic stem cell transplantation.
      Transplant centres have accumulated increasing expertise in their understanding
      of umbilical cord blood characteristics that are associated with improved outcome
      following transplantation. These characteristics and factors can assist
      transplant centres in selecting cord blood units from the worldwide inventory of
      banked units. Umbilical cord blood banks, therefore, need to remain agile in
      adjusting the inventory of the banks to address shifts or changes in the needs of
      transplant centres. Public umbilical cord blood banks face the challenge of
      building inventory while managing limited resources and are faced with decisions
      regarding which units can be stored and which units that have been collected
      should be discarded or used for other endeavours such as research. To this end,
      we sought to review parameters influencing the decision to bank a collected cord
      blood unit. In this paper, we will address parameters associated with graft
      potency and address other factors that guide the decision to bank collected
      units.

PMID- 23533443
TI  - The Assessment of Parameters Affecting the Quality of Cord Blood by the Appliance
      of the Annexin V Staining Method and Correlation with CFU Assays.
AB  - The assessment of nonviable haematopoietic cells by Annexin V staining method in
      flow cytometry has recently been published by Duggleby et al. Resulting in a
      better correlation with the observed colony formation in methylcellulose assays
      than the standard ISHAGE protocol, it presents a promising method to predict cord
      blood potency. Herein, we applied this method for examining the parameters during
      processing which potentially could affect cord blood viability. We could verify
      that the current standards regarding time and temperature are sufficient, since
      no significant difference was observed within 48 hours or in storage at 4 degrees
      C up to 26 degrees C. However, the addition of DMSO for cryopreservation alone
      leads to an inevitable increase in nonviable haematopoietic stem cells from
      initially 14.8% +/- 4.3% to at least 30.6% +/- 5.5%. Furthermore, CFU-assays with
      varied seeding density were performed in order to evaluate the applicability as a
      quantitative method. The results revealed that only in a narrow range
      reproducible clonogenic efficiency (ClonE) could be assessed, giving at least a
      semiquantitative estimation. We conclude that both Annexin V staining method and
      CFU-assays with defined seeding density are reliable means leading to a better
      prediction of the final potency. Especially Annexin V, due to its fast readout,
      is a practical tool for examining and optimising specific steps in processing,
      while CFU-assays add a functional confirmation.

PMID- 23533444
TI  - Webuye Health and Demographic Surveillance Systems Baseline Survey of Soil
      Transmitted Helminths and Intestinal Protozoa among Children up to Five Years.
AB  - Background. The intestinal parasitic infections (IPIs) are globally endemic, and
      they constitute the greatest cause of illness and disease worldwide. Transmission
      of IPIs occurs as a result of inadequate sanitation, inaccessibility to potable
      water, and poor living conditions. Objectives. To determine a baseline prevalence
      of IPIs among children of five years and below at Webuye Health and Demographic
      Surveillance (HDSS) area in western Kenya. Methods. Cross-sectional survey was
      used to collect data. Direct saline and formal-ether-sedimentation techniques
      were used to process the specimens. Descriptive and inferential statistics such
      as Chi-square statistics were used to analyze the data. Results. A prevalence of
      52.3% (417/797) was obtained with the male child slightly more infected than the
      female (53.5% versus 51%), but this was not significant (chi (2) = 0.482, P >
      0.05). Giardia lamblia and Entamoeba histolytica were the most common pathogenic
      IPIs with a prevalence of 26.1% (208/797) and 11.2% (89/797), respectively. Soil
      transmitted helminths (STHs) were less common with a prevalence of 4.8% (38/797),
      3.8% (30/797), and 0.13% (1/797) for Ascaris lumbricoides, hookworms, and
      Trichuris trichiura, respectively. Conclusions. Giardia lamblia and E.
      histolytica were the most prevalent pathogenic intestinal protozoa, while STHs
      were less common. Community-based health promotion techniques are recommended for
      controlling these parasites.

PMID- 23533441
TI  - Cancer stem cell markers in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is one of the world's top ten most
      common cancers. Current survival rates are poor with only 50% of patients
      expected to survive five years after diagnosis. The poor survival rate of HNSCC
      is partly attributable to the tendency for diagnosis at the late stage of the
      disease. One of the reasons for treatment failure is thought to be related to the
      presence of a subpopulation of cells within the tumour called cancer stem cells
      (CSCs). CSCs display stem cell-like characteristics that impart resistance to
      conventional treatment modalities and promote tumour initiation, progression, and
      metastasis. Specific markers for this population have been investigated in the
      hope of developing a deeper understanding of their role in the pathogenesis of
      HNSCC and elucidating novel therapeutic strategies.

PMID- 23533445
TI  - Immunological characteristics of hyperreactive malarial splenomegaly syndrome in
      sudanese patients.
AB  - Hyperreactive Malarial Splenomegaly (HMS) is defined as a massive enlargement of
      the spleen resulting from abnormal immune responses after repeated exposure to
      the malaria parasites. This study was carried out in Khartoum, Sudan. Sudan is
      considered to be one of the countries where HMS is quite prevalent. The objective
      of the study was to determine the incidence of HMS in patients who reported to
      the Omdurman Tropical Diseases Hospital (OMTDH) in Sudan and to investigate the
      basic laboratory and immunological characteristics of this condition in these
      patients. A cross-sectional study was carried out in OMTDH, and all patients with
      enlarged spleens were included in the study. Thirty-one out of 335 (9.3%)
      patients were diagnosed as having the HMS condition using international criteria
      for HMS diagnosis. The mean serum immunoglobulin M (IgM) levels in HMS patient
      groups were 14.3 +/- 5 g/L, and this was significantly higher compared with
      geographically matched controls (P < 0.001). Immunoglobulin G (IgG) C
      anticircumsporozoite (CSP) antibody levels were higher in the HMS patients
      although the difference was not statistically significant, when compared with a
      group of patients with mild malaria. In comparison with naive European controls,
      both the HMS and the mild malaria groups had significantly higher antimalarial
      antibody levels P < 0.001 and P < 0.01, respectively. Plasma levels of
      interleukin 10 (IL10) and interferon gamma (IFN gamma ) were significantly
      increased in the HMS patients compared with the healthy control donors (P < 0.05
      and P < 0.01) for IL10 and IFN gamma , respectively. The findings of this study
      suggest that HMS is one of the significant causes of tropical splenomegaly in
      Sudan. HMS is associated with significant elevations of circulating IgM and
      antimalarial IgG antibodies as well as IL10 and IFN gamma .

PMID- 23533446
TI  - Role of antidiarrhoeal drugs as adjunctive therapies for acute diarrhoea in
      children.
AB  - Acute diarrhoea is a leading cause of child mortality in developing countries.
      Principal pathogens include Escherichia coli, rotaviruses, and noroviruses. 90%
      of diarrhoeal deaths are attributable to inadequate sanitation. Acute diarrhoea
      is the second leading cause of overall childhood mortality and accounts for 18%
      of deaths among children under five. In 2004 an estimated 1.5 million children
      died from diarrhoea, with 80% of deaths occurring before the age of two.
      Treatment goals are to prevent dehydration and nutritional damage and to reduce
      duration and severity of diarrhoeal episodes. The recommended therapeutic regimen
      is to provide oral rehydration solutions (ORS) and to continue feeding. Although
      ORS effectively mitigates dehydration, it has no effect on the duration,
      severity, or frequency of diarrhoeal episodes. Adjuvant therapy with
      micronutrients, probiotics, or antidiarrhoeal agents may thus be useful. The WHO
      recommends the use of zinc tablets in association with ORS. The ESPGHAN/ESPID
      treatment guidelines consider the use of racecadotril, diosmectite, or probiotics
      as possible adjunctive therapy to ORS. Only racecadotril and diosmectite reduce
      stool output, but no treatment has yet been shown to reduce hospitalisation rate
      or mortality. Appropriate management with validated treatments may help reduce
      the health and economic burden of acute diarrhoea in children worldwide.

PMID- 23533447
TI  - Systemic ghrelin administration alters serum biomarkers of angiogenesis in diet
      induced obese mice.
AB  - Introduction. Ghrelin is a gastrointestinal endocrine peptide that was initially
      identified as the endogenous ligand of growth hormone secretagogue receptor;
      however, recently, the cardiovascular effect of this peptide has been indicated.
      In this study, we investigated the effect of ghrelin administration on serum
      biomarkers of angiogenesis including leptin, nitric oxide (NO), vascular
      endothelial growth factor (VEGF), and its soluble receptor (VEGF receptor 1 or
      sFlt-1) in control- and diet-induced obese mice. Methods. Male C57BL/6 mice were
      randomly divided into four groups, normal diet (ND) or control, ND + ghrelin,
      high-fat-diet (HFD) or obese and HFD + ghrelin (n = 6/group). Obese and control
      groups received either HFD or ND for 15 weeks. Then, the ghrelin was injected
      subcutaneously 100 ug/kg twice daily for 10 days. At the end of experiment, blood
      samples were collected for blood glucose, serum insulin, VEGF, sFlt-1, NO, and
      leptin measurements. Results. The obese animals had higher serum NO and leptin
      concentrations without changes in serum VEGF and sFlt-1 levels compared to
      control. Administration of ghrelin significantly increased serum VEGF and
      decreased serum leptin and NO concentrations in HFD group. Conclusion. Since
      ghrelin changes serum biomarkers of angiogenesis, it seems that it gets involved
      during states with abnormal angiogenesis.

PMID- 23533448
TI  - Phage Display Screening for Tumor Necrosis Factor- alpha -Binding Peptides:
      Detection of Inflammation in a Mouse Model of Hepatitis.
AB  - TNF- alpha is one of the most abundant cytokines produced in many inflammatory
      and autoimmune conditions such as multiple sclerosis, chronic hepatitis C, or
      neurodegenerative diseases. These pathologies remain difficult to diagnose and
      consequently difficult to treat. The aim of this work is to offer a new
      diagnostic tool by seeking new molecular probes for medical imaging. The target
      specific part of the probe consists here of heptameric peptides selected by the
      phage display technology for their affinity for TNF- alpha . Several affinity
      tests allowed isolating 2 peptides that showed the best binding capacity to TNF-
      alpha . Finally, the best peptide was synthesized in both linear and cyclic forms
      and tested on the histological sections of concanavalin-A-(ConA-)treated mice
      liver. In this well-known hepatitis mouse model, the best results were obtained
      with the cyclic form of peptide 2, which allowed for the staining of inflamed
      areas in the liver. The cyclic form of peptide 2 (2C) was, thus, covalently
      linked to iron oxide nanoparticles (magnetic resonance imaging (MRI) contrast
      agent) and tested in the ConA-induced hepatitis mouse model. The vectorized
      nanoparticles allowed for the detection of inflammation as well as of the free
      peptide. These ex vivo results suggest that phage display-selected peptides can
      direct imaging contrast agents to inflammatory areas.

PMID- 23533449
TI  - alpha -RgIB: A Novel Antagonist Peptide of Neuronal Acetylcholine Receptor
      Isolated from Conus regius Venom.
AB  - Conus venoms are rich sources of biologically active peptides that act
      specifically on ionic channels and metabotropic receptors present at the
      neuromuscular junction, efficiently paralyzing the prey. Each species of Conus
      may have 50 to 200 uncharacterized bioactive peptides with pharmacological
      interest. Conus regius is a vermivorous species that inhabits Northeastern
      Brazilian tropical waters. In this work, we characterized one peptide with
      activity on neuronal acetylcholine receptor (nAChR). Crude venom was purified by
      reverse-phase HPLC and selected fractions were screened and sequenced by mass
      spectrometry, MALDI-ToF, and ESI-Q-ToF, respectively. A new peptide was
      identified, bearing two disulfide bridges. The novel 2,701 Da peptide belongs to
      the cysteine framework I, corresponding to the cysteine pattern CC-C-C. The
      biological activity of the purified peptide was tested by intracranial injection
      in mice, and it was observed that high concentrations induced hyperactivity in
      the animals, whereas lower doses caused breathing difficulty. The activity of
      this peptide was assayed in patch-clamp experiments, on nAChR-rich cells, in
      whole-cell configuration. The peptide blocked slow rise-time neuronal receptors,
      probably alpha 3 beta 4 and/or alpha 3 beta 4 alpha 5 subtype. According to the
      nomenclature, the new peptide was designated as alpha -RgIB.

PMID- 23533451
TI  - Smokeless tobacco and dual use among firefighters in the central United States.
AB  - Little is known about smokeless tobacco (SLT) use in the fire service, whose
      personnel need to maintain high levels of health and fitness given the rigorous
      physical and mental job requirements. We examined the relationships among
      variables associated with SLT use and dual tobacco use (SLT and smoking) among
      353 male career firefighters. Around 13% of male career firefighters reported
      being current exclusive SLT users, and 2.6% used both cigarettes and SLT. Age
      adjusted models revealed that race, binge drinking, and dietary fat consumption
      were positively associated with exclusive SLT use when compared to nontobacco
      users. SLT users were much more likely to binge drink (OR = 3.98, P < .01) and
      consume high fat foods (OR = 1.94, P < .05). Only high dietary fat consumption
      was a strong correlate (OR = 8.41, P < .05) of dual use when compared to
      nontobacco users. SLT and dual tobacco use are associated with significant health
      risks. Detailed information on the predictors of SLT use among firefighters will
      aid in developing more effective tobacco prevention and cessation intervention in
      fire service.

PMID- 23533450
TI  - Health-related factors associated with mode of travel to work.
AB  - Active commuting (AC) to the workplace is a potential strategy for incorporating
      physical activity into daily life and is associated with health benefits. This
      study examined the association between health-related factors and mode of travel
      to the workplace. Methods. A volunteer convenience sample of employed adults
      completed an online survey regarding demographics, health-related factors, and
      the number of times/week walking, biking, driving, and using public transit to
      work (dichotomized as no walk/bike/drive/PT and walk/bike/drive/PT 1 + x/week).
      Logistic regression was used to predict the likelihood of each mode of transport
      and meeting PA recommendations from AC according to demographics and health
      related factors. Results. The sample (n = 1175) was aged 43.5 +/- 11.4 years and
      was primarily White (92.7%) and female (67.9%). Respondents reported walking
      (7.3%), biking (14.4%), taking public transit (20.3%), and driving (78.3%) to
      work at least one time/week. Among those reporting AC, 9.6% met PA
      recommendations from AC alone. Mode of travel to work was associated with several
      demographic and health-related factors, including age, number of chronic
      diseases, weight status, and AC beliefs. Discussion. Mode of transportation to
      the workplace and health-related factors such as disease or weight status should
      be considered in future interventions targeting AC.

PMID- 23533452
TI  - Study of the bioremediation of atrazine under variable carbon and nitrogen
      sources by mixed bacterial consortium isolated from corn field soil in Fars
      province of Iran.
AB  - Atrazine herbicide that is widely used in corn production is frequently detected
      in water resources. The main objectives of this research were focused on
      assessing the effects of carbon and nitrogen sources on atrazine biodegradation
      by mixed bacterial consortium and by evaluating the feasibility of using mixed
      bacterial consortium in soil culture. Shiraz corn field soil with a long history
      of atrazine application has been explored for their potential of atrazine
      biodegradation. The influence of different carbon compounds and the effect of
      nitrogen sources and a different pH (5.5-8.5) on atrazine removal efficiency by
      mixed bacterial consortium in liquid culture were investigated. Sodium citrate
      and sucrose had the highest atrazine biodegradation rate (87.22%) among different
      carbon sources. Atrazine biodegradation rate decreased more quickly by the
      addition of urea (26.76%) compared to ammonium nitrate. Based on the data
      obtained in this study, pH of 7.0 is optimum for atrazine biodegradation. After
      30 days of incubation, the percent of atrazine reduction rates were significantly
      enhanced in the inoculated soils (60.5%) as compared to uninoculated control
      soils (12%) at the soil moisture content of 25%. In conclusion, bioaugmentation
      of soil with mixed bacterial consortium may enhance the rate of atrazine
      degradation in a highly polluted soil.

PMID- 23533453
TI  - Infection and coinfection of human rhinovirus C in stem cell transplant
      recipients.
AB  - In 54 adult stem cell transplant recipients, the presence and persistence of
      human rhinoviruses (including the novel lineage C) were evaluated by molecular
      detection and phylogenetic analysis, independently from respiratory symptoms. In
      the same group of patients, the presence of other coinfecting respiratory
      pathogens, including the novel enterovirus 109, was also evaluated.

PMID- 23533454
TI  - Chitin, chitosan, and glycated chitosan regulate immune responses: the novel
      adjuvants for cancer vaccine.
AB  - With the development of cancer immunotherapy, cancer vaccine has become a novel
      modality for cancer treatment, and the important role of adjuvant has been
      realized recently. Chitin, chitosan, and their derivatives have shown their
      advantages as adjuvants for cancer vaccine. In this paper, the adjuvant
      properties of chitin and chitosan were discussed, and some detailed information
      about glycated chitosan and chitosan nanoparticles was also presented to
      illustrate the trend for future development.

PMID- 23533455
TI  - Posttransplant lymphoproliferative disease after lung transplantation.
AB  - Posttransplant lymphoproliferative disease (PTLD) after lung transplantation
      occurs due to immunosuppressant therapy which limits antiviral host immunity and
      permits Epstein-Barr viral (EBV) replication and transformation of B cells.
      Mechanistically, EBV survives due to latency, escape from cytotoxic T cell
      responses, and downregulation of host immunity to EBV. Clinical presentation of
      EBV may occur within the lung allograft early posttransplantation or later onset
      which is more likely to be disseminated. Improvements in monitoring through EBV
      viral load have provided a means of earlier detection; yet, sensitivity and
      specificity of EBV load monitoring after lung transplantation may require further
      optimization. Once PTLD develops, staging and tissue diagnosis are essential to
      appropriate histopathological classification, prognosis, and guidance for
      therapy. The overall paradigm to treat PTLD has evolved over the past several
      years and depends upon assessment of risk such as EBV-naive status, clinical
      presentation, and stage and sites of disease. In general, clinical practice
      involves reduction in immunosuppression, anti-CD20 biologic therapy, and/or use
      of plasma cell inhibition, followed by chemotherapy for refractory PTLD. This
      paper focuses upon the immunobiology of EBV and PTLD, as well as the clinical
      presentation, diagnosis, prognosis, and emerging treatments for PTLD after lung
      transplantation.

PMID- 23533457
TI  - Time-dependent effect of oral morphine consumption on the development of
      cytotrophoblast and syncytiotrophoblast cells of the placental layers during the
      three different periods of pregnancy in Wistar rats.
AB  - Previous studies have shown that morphine abuse during pregnancy cancause a delay
      in the development of the placenta and embryo and also bring about birth defects.
      The present study investigates the effect of the duration of maternal morphine
      consumption during pregnancy, as well as the impacts of morphine abuse on the
      development of placental layers during the three different periods of pregnancy
      in Wistar rats. MATERIALS AND METHODOLOGY: Female Wistar rats have been used in
      the present study. Experimental groups received morphine (0.05 mg/mL of drinking
      water) after one night of coupling with male rats for mating. On 9th, 10th, and
      14th days of pregnancy, pregnant animals were killed, and placentas were removed
      and fixed. The cells of the placentas layers were calculated by light microscope
      and MOTIC and SPSS software. RESULTS: The maternal surface thickness of the
      placenta was significantly increased, whereasthe fetal surface thickness of
      placenta was significantly decreased with morphine consumption with a time
      dependent manner in experimental groups, compared to control groups. Moreover,
      the number of trophoblast cells increased in both maternal and fetal surfaces of
      placenta with respect to the duration of morphine consumption which was overt in
      the experimental groups compared to the control groups. CONCLUSION: In general,
      the time-dependent effects of oral morphine consumption can inhibit the
      development and natural functioning of cytotrophoblast and syncytiotrophoblast
      cells of the placental layers.

PMID- 23533458
TI  - Roles of gammadelta T cells in the pathogenesis of autoimmune diseases.
AB  - gammadelta T cells are a minor population of T cells that express the TCR
      gammadelta chains, mainly distributed in the mucosal and epithelial tissue and
      accounting for less than 5% of the total T cells in the peripheral blood. By
      bridging innate and adaptive immunity, gammadelta T cells play important roles in
      the anti-infection, antitumor, and autoimmune responses. Previous research on
      gammadelta T cells was primarily concentrated on infectious diseases and tumors,
      whereas their functions in autoimmune diseases attracted much attention. In this
      paper, we summarized the various functions of gammadelta T cells in two
      prototypical autoimmune connective tissue diseases, that is, SLE and RA,
      elaborating on their antigen-presenting capacity, secretion of proinflammatory
      cytokines, immunomodulatory effects, and auxiliary function for B cells, which
      contribute to overproduction of proinflammatory cytokines and pathogenic
      autoantibodies, ultimately leading to the onset of these autoimmune diseases.
      Elucidation of the roles of gammadelta T cells in autoimmune diseases is not only
      conducive to in-depth understanding of the pathogenesis of these diseases, but
      also beneficial in providing theoretical support for the development of
      gammadelta T-cell-targeted therapy.

PMID- 23533459
TI  - Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension.
AB  - Hypertension increases the risk for a variety of cardiovascular diseases,
      including stroke, coronary artery disease, heart failure, and peripheral vascular
      disease. The increase in oxidative stress has been associated with the
      pathogenesis of hypertension. Increase of blood pressure is due to an imbalance
      between antioxidants defence mechanisms and free radical productions. Excessive
      production of reactive oxygen species reduces nitric oxide bioavailability
      leading to an endothelial dysfunction and a subsequent increase in total
      peripheral resistance. Hypertension can cause few symptoms until it reaches the
      advanced stage and poses serious health problems with lifelong consequences.
      Hypertensive patients are required to take drugs for life to control the
      hypertension and prevent complications. Some of these drugs are expensive and may
      have adverse reactions. Hence, it is timely to examine scientifically,
      complimentary therapies that are more effective and with minimal undesirable
      effects. Nigella sativa (NS) and its active constituents have been documented to
      exhibit antioxidant, hypotensive, calcium channel blockade and diuretic
      properties which may contribute to reduce blood pressure. This suggests a
      potential role of NS in the management of hypertension, and thus more studies
      should be conducted to evaluate its effectiveness.

PMID- 23533456
TI  - Modulation of tumor immunity by soluble and membrane-bound molecules at the
      immunological synapse.
AB  - To circumvent pathology caused by infectious microbes and tumor growth, the host
      immune system must constantly clear harmful microorganisms and potentially
      malignant transformed cells. This task is accomplished in part by T-cells, which
      can directly kill infected or tumorigenic cells. A crucial event determining the
      recognition and elimination of detrimental cells is antigen recognition by the T
      cell receptor (TCR) expressed on the surface of T cells. Upon binding of the TCR
      to cognate peptide-MHC complexes presented on the surface of antigen presenting
      cells (APCs), a specialized supramolecular structure known as the immunological
      synapse (IS) assembles at the T cell-APC interface. Such a structure involves
      massive redistribution of membrane proteins, including TCR/pMHC complexes,
      modulatory receptor pairs, and adhesion molecules. Furthermore, assembly of the
      immunological synapse leads to intracellular events that modulate and define the
      magnitude and characteristics of the T cell response. Here, we discuss recent
      literature on the regulation and assembly of IS and the mechanisms evolved by
      tumors to modulate its function to escape T cell cytotoxicity, as well as novel
      strategies targeting the IS for therapy.

PMID- 23533460
TI  - Cardiovascular Protective Effects of Adjunctive Alternative Medicine (Salvia
      miltiorrhiza and Pueraria lobata) in High-Risk Hypertension.
AB  - Introduction. Hypertension in association with diabetes (DM), renal impairment
      (RI), and left ventricular hypertrophy (LVH) increases the risk of future
      cardiovascular events. We hypothesize, traditional herbal medicines Danshen and
      Gegen (D&G) have beneficial effects on atherogenesis in these high-risk
      hypertensive subjects. Subjects and Methods. 90 asymptomatic hypertensive
      subjects associated with LVH (63.3%), DM (62.2%), or RI (30%) were randomized to
      receive D&G herbal capsules 1 gm/day, 2 gm/day, or identical placebo capsules in
      double-blind and parallel fashion for 12 months. Brachial flow-mediated dilation
      (endothelium-dependent dilation, FMD) and carotid intima-media thickness (IMT)
      were measured by ultrasound. All data were analyzed using the Statistical Package
      for Social Sciences in Windows 16.0. Results. Their mean age was 55 +/- 8 years,
      and 74.4% were male. After 12 months of adjunctive therapies and compared with
      baseline, there were no significant changes in blood pressure, heart rate,
      hematological, glucose, and creatinine profiles in both placebo and D&G groups.
      FMD improved significantly during D&G (P = 0.0001) and less so after placebo
      treatment (P = 0.001). There was a mild but significant decrease in carotid IMT
      after D&G (P < 0.001) but no significant changes after placebo. A trend of better
      improvement in FMD after higher versus lower D&G dosages was seen. D&G were well
      tolerated, with no significant adverse events or blood biochemistry changes.
      Conclusion. D&G adjunctive treatment was well tolerated and significantly
      improved atherogenesis in high-risk hypertensive patients, with potential in
      primary atherosclerosis prevention.

PMID- 23533461
TI  - Effects of qigong on depression: a systemic review.
AB  - Physical exercises and relaxation have been found to be beneficial for
      depression. However, there is little evidence on the use of Qigong, a mind-body
      practice integrating gentle exercise and relaxation, in the management of
      depression. The aim of this paper is to evaluate the effects of Qigong on
      depression. The paper examined clinical trials measuring the effect of Qigong on
      depression within six large-scale medical research databases (PubMed, Medline,
      ProQuest, Science Direct, EMBASE, and PsycInfo) till October 2011. Key words
      "Qigong," "depression," and "mood" were used. Ten studies were identified as
      original randomized controlled trial (RCT) studies investigating the effect of
      Qigong on depression as primary (n = 2) or secondary outcome (n = 8). Four
      studies reported positive results of the Qigong treatment on depression; two
      reported that Qigong effect on depression was as effective as physical exercise.
      One study reported that Qigong was comparable to a conventional rehabilitation
      program, but the remaining three studies found no benefits of Qigong on
      depression. While the evidence suggests the potential effects of Qigong in the
      treatment of depression, the review of the literature shows inconclusive results.
      Further research using rigorous study designs is necessary to investigate the
      effectiveness of Qigong in depression.

PMID- 23533462
TI  - Replacements of rare herbs and simplifications of traditional chinese medicine
      formulae based on attribute similarities and pathway enrichment analysis.
AB  - A Traditional Chinese Medicine (TCM) formula is a collection of several herbs.
      TCM formulae have been used to treat various diseases for several thousand years.
      However, wide usage of TCM formulae has results in rapid decline of some rare
      herbs. So it is urgent to find common available replacements for those rare herbs
      with the similar effects. In addition, a formula can be simplified by reducing
      herbs with unchanged effects. Based on this consideration, we propose a method,
      called "formula pair," to replace the rare herbs and simplify TCM formulae. We
      show its reasonableness from a perspective of pathway enrichment analysis. Both
      the replacements of rare herbs and simplifications of formulae provide new
      approaches for a new formula discovery. We demonstrate our approach by replacing
      a rare herb "Forsythia suspensa" in the formula "the seventh of Sang Ju Yin
      plus/minus herbs (SSJY)" with a common herb "Thunberg Fritillary Bulb" and
      simplifying two formulae, "the fifth of Du Huo Ji Sheng Tang plus/minus herbs
      (FDHJST)" and "Fang Feng Tang" (FFT) to a new formula "Fang Feng Du Huo Tang"
      (FFDHT).

PMID- 23533463
TI  - Chemistry and biology of essential oils of genus boswellia.
AB  - The properties of Boswellia plants have been exploited for millennia in the
      traditional medicines of Africa, China, and especially in the Indian Ayurveda. In
      Western countries, the advent of synthetic drugs has obscured the pharmaceutical
      use of Boswellia, until it was reported that an ethanolic extract exerts anti
      inflammatory and antiarthritic effects. Frankincense was commonly used for
      medicinal purposes. This paper aims to provide an overview of current knowledge
      of the volatile constituents of frankincense, with explicit consideration
      concerning the diverse Boswellia species. Altogether, more than 340 volatiles in
      Boswellia have been reported in the literature. In particular, a broad diversity
      has been found in the qualitative and quantitative composition of the volatiles
      with respect to different varieties of Boswellia. A detailed discussion of the
      various biological activities of Boswellia frankincense is also presented.

PMID- 23533464
TI  - Yes, there is deqi sensation in laser acupuncture.
AB  - Deqi, a composite of unique sensations, is essential for clinical efficacy
      according to Traditional Chinese Medicine. It is described as a sensory
      perception of varying character and is mostly ascribed to metal needle
      acupuncture. However, it can also be elicited by different kinds of laser
      acupuncture stimulation. This short paper summarizes the current scientific
      status of deqi in laser stimulation. Different kinds of laser acupuncture are
      described in a comprehensive form, and the most interesting studies concerning
      deqi and laser acupuncture are presented.

PMID- 23533465
TI  - Medical yoga for patients with stress-related symptoms and diagnoses in primary
      health care: a randomized controlled trial.
AB  - An increasing number of patients are suffering from stress-related symptoms and
      diagnoses. The purpose of this study was to evaluate the medical yoga treatment
      in patients with stress-related symptoms and diagnoses in primary health care. A
      randomized controlled study was performed at a primary health care centre in
      Sweden from March to June, 2011. Patients were randomly allocated to a control
      group receiving standard care or a yoga group treated with medical yoga for 1
      hour, once a week, over a 12-week period in addition to the standard care. A
      total of 37 men and women, mean age of 53 +/- 12 years were included. General
      stress level (measured using Perceived Stress Scale (PSS)), burnout (Shirom
      Melamed Burnout Questionnaire (SMBQ)), anxiety and depression (Hospital Anxiety
      and Depression Scale (HADS)), insomnia severity (Insomnia Severity Index (ISI)),
      pain (visual analogue scale (VAS)), and overall health status (Euro Quality of
      Life VAS (EQ-VAS)) were measured before and after 12 weeks. Patients assigned to
      the Yoga group showed significantly greater improvements on measures of general
      stress level (P < 0.000), anxiety (P < 0.019), and overall health status (P <
      0.018) compared to controls. Treatment with medical yoga is effective in reducing
      levels of stress and anxiety in patients with stress-related symptoms in primary
      health care.

PMID- 23533466
TI  - Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer
      Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis.
AB  - The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such
      as gefitinib and erlotinib, have shown promising therapeutic efficacy in nonsmall
      cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor-
      (EGFR-) activating mutation. However, the inevitable recurrence resulting from
      acquired resistance has limited the clinical improvement in therapy outcomes.
      Many studies demonstrate that hepatocyte growth factor- (HGF-) Met axis plays an
      important role in tumor progression and drug sensitivity. HGF may induce
      resistance to EGFR-TKIs in EGFR mutant lung cancer cells by Met/PI3K/Akt
      signaling. The purpose of this study was to determine whether bufalin, a major
      bioactive component of Venenum Bufonis, could reverse HGF-induced resistance to
      reversible and irreversible EGFR-TKIs in mutant lung cancer cells PC-9, HCC827,
      and H1975. Our studies showed that bufalin could reverse resistance to reversible
      and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer
      cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. These
      results suggested that bufalin might have a potential to overcome HGF-induced
      resistance to molecular-targeted drugs for lung cancer.

PMID- 23533467
TI  - Reduction of Airway Hyperresponsiveness by KWLL in Dermatophagoides-pteronyssinus
      Challenged Mice.
AB  - Urine therapy has been commonly practiced in ancient civilizations including
      those of India, China, and Greece. The traditional Chinese medicine KWLL, the
      precipitation of human urine, has been used in China to alleviate the symptoms of
      asthma for thousands of years. However, the mechanism of action by which KWLL
      exerts its immunotherapy is unclear. This study attempted to elucidate the
      pharmacology of KWLL in mice that had been challenged recurrently by
      Dermatophagoides pteronyssinus (Der p). BALB/c mice were orally administered KWLL
      (1 g/kg) before an intratracheal (i.t.) challenge of Der p. Allergic airway
      inflammation and remodeling were provoked by repetitive Der p (50  MU g/mice)
      challenges six times at 1 wk intervals. Airway hypersensitivity, histological
      lung characteristics, and the expression profiles of cytokines and various genes
      were assessed. KWLL reduced Der p-induced airway hyperresponsiveness and
      inhibited eosinophil infiltration by downregulating the protein expression of IL
      5 in bronchoalveolar lavage fluid (BALF). It also inhibited neutrophil
      recruitment by downregulating IL-17A in BALF. KWLL effectively diminished
      inflammatory cells, goblet cell hyperplasia, and mRNA expression of IL-6 and IL
      17A in the lung. The reduction by KWLL of airway inflammatory and
      hyperresponsiveness in allergic asthmatic mice was mediated via immunomodulation
      of IL-5, IL-6, and IL-17A.

PMID- 23533468
TI  - Osthole Improves Spatial Memory Deficits in Rats via Hippocampal alpha 1
      Adrenergic and D 1 /D 2 Receptors.
AB  - The present study evaluated the effect of osthole, an active ingredient isolated
      from Cnidium monnieri L. Cusson, on spatial memory deficits caused by central
      neurotoxins using the Morris water maze in rats. The involvement of
      catecholaminergic receptors on the memory-enhancing effect of osthole in rat
      hippocampus was further investigated by intrahippocampal injection of
      catecholaminergic receptor antagonists. Intracisternal injection of osthole (10 
      MU g/brain) improved the spatial performance and working memory impairments
      caused by the catecholaminergic neurotoxin 6-hydroxydopamine. No significant
      differences in swimming speeds were observed among sham, neurotoxin-induced, and
      osthole-treated groups. Intracisternal osthole injection also attenuated the
      spatial performance and working memory impairments caused by the alpha 1 receptor
      antagonist phenoxybenzamine, the D1 receptor antagonist SCH 23390, and the D2
      receptor antagonist sulpiride. Therefore, we demonstrated that the effect of
      osthole on improving spatial memory deficits may be related to the activation of
      hippocampal alpha 1 and D1/D2 receptors.

PMID- 23533469
TI  - Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects
      on Leishmania amazonensis and Possible Mechanisms of Action.
AB  - Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as
      Brazilian cherry tree. In this study, we evaluated the chemical composition of
      Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass
      spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored
      the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds
      were identified, which constituted 92.65% of the total oil composition. The most
      abundant components were sesquiterpenes (91.92%), with curzerene (47.3%), gamma 
      elemene (14.25%), and trans- beta -elemenone (10.4%) being the major
      constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04  MU
      g.mL(-1)) and amastigotes (IC50, 1.92  MU g.mL(-1)) suggested significant anti
      Leishmania activity. In the cytotoxicity determination, EuEO was 20 times more
      toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the
      highest concentration tested (400  MU g.mL(-1)); however, there appeared to be no
      toxicity at 50  MU g.mL(-1). While the data show that EuEO activity is not
      mediated by nitric oxide production, they do suggest that macrophage activation
      may be involved in EuEO anti-Leishmania activity, as evidenced by increases in
      both the phagocytic capacity and the lysosomal activity. More studies are needed
      to determine in vivo activity as well as additional mechanisms of the anti
      Leishmania activity.

PMID- 23533470
TI  - Carvacrol Protects against Hepatic Steatosis in Mice Fed a High-Fat Diet by
      Enhancing SIRT1-AMPK Signaling.
AB  - We investigated the protective effect of carvacrol against high-fat-diet-induced
      hepatic steatosis in mice and the potential underlying molecular mechanisms. Mice
      were fed a normal diet, high-fat diet, or carvacrol-supplemented high-fat diet
      for 10 weeks. Compared to mice fed the high-fat diet, those fed the carvacrol
      supplemented diet showed significantly lower hepatic lipid levels and reduced
      plasma activities of alanine aminotransferase and aspartate aminotransferase and
      plasma concentrations of monocyte chemoattractant protein 1 and tumor necrosis
      factor alpha . Carvacrol decreased the expression of LXR alpha , SREBP1c, FAS,
      leptin, and CD36 genes and phosphorylation of S6 kinase 1 protein involved in
      lipogenesis, whereas it increased the expression of SIRT1 and CPT1 genes and
      phosphorylation of liver kinase B1, AMP-activated protein kinase, and acetyl-CoA
      carboxylase proteins involved in fatty acid oxidation in the liver of mice fed
      the high-fat diet. These results suggest that carvacrol prevents HFD-induced
      hepatic steatosis by activating SIRT1-AMPK signaling.

PMID- 23533471
TI  - Propolis induces chondroitin/dermatan sulphate and hyaluronic Acid accumulation
      in the skin of burned wound.
AB  - Changes in extracellular matrix glycosaminoglycans during the wound repair
      allowed us to apply the burn model in which therapeutic efficacy of propolis and
      silver sulfadiazine was compared. Burns were inflicted on four pigs.
      Glycosaminoglycans isolated from healthy and burned skin were quantified using a
      hexuronic acid assay, electrophoretic fractionation, and densitometric analyses.
      Using the reverse-phase HPLC the profile of sulfated disaccharides released by
      chondroitinase ABC from chondroitin/dermatan sulfates was estimated.
      Chondroitin/dermatan sulfates and hyaluronic acid were found in all samples.
      Propolis stimulated significant changes in the content of particular
      glycosaminoglycan types during burn healing. Glycosaminoglycans alterations after
      silver sulfadiazine application were less expressed. Propolis maintained high
      contribution of 4-O-sulfated disaccharides to chondroitin/dermatan sulfates
      structure and low level of 6-O-sulfated ones throughout the observed period of
      healing. Propolis led to preservation of significant contribution of disulfated
      disaccharides especially 2,4-O-disulfated ones to chondroitin sulfates/dermatan
      sulfates structure throughout the observed period of healing. Our findings
      demonstrate that propolis accelerates the burned tissue repair by stimulation of
      the wound bed glycosaminoglycan accumulation needed for granulation, tissue
      growth, and wound closure. Moreover, propolis accelerates chondroitin/dermatan
      sulfates structure modification responsible for binding growth factors playing
      the crucial role in the tissue repair.

PMID- 23533472
TI  - Efficacy of Plectranthus amboinicus (Lour.) Spreng in a Murine Model of
      Methicillin-Resistant Staphylococcus aureus Skin Abscesses.
AB  - The present work aimed to evaluate the effectiveness of Plectranthus amboinicus
      (Lour.) Spreng against MRSA clinical isolates. The in vitro antimicrobial
      activity of the hydroalcoholic extract (HE), the ethyl acetate (EA) fraction and
      its subfractions were determined by broth microdilution and bioautography against
      MRSA clinical isolates. The microdilution checkerboard method was used to assess
      in vitro drug combination studies. To induce abscess formation, bacterial
      suspensions were added to Citodex and inoculated subcutaneously into male Swiss
      mice. The treatment protocol consisted of 2 doses of HE, the EA fraction or
      vancomycin introduced intraperitoneally into mice 3 and 12 h after infection. The
      EA fraction and its subfractions presented the lowest minimal inhibitory
      concentrations (MIC, 0.25 to 0.5 mg/mL). The plant samples were bacteriostatic at
      2x and 4x MIC and bactericidal at 100 mg/mL. The EA fraction presented synergism
      with vancomycin and an additive effect with ciprofloxacin. A significant
      reduction of abscess volume, bacterial cell counts in abscess slurries, and
      inflammatory scores was observed in the HE and EA fraction-treated groups. The
      samples were effective in treating the animals in a dose-dependent fashion. The
      present study proved the effectiveness of P. amboinicus fractions against MRSA
      using in vitro and in vivo assays.

PMID- 23533473
TI  - Roots of Erigeron annuus Attenuate Acute Inflammation as Mediated with the
      Inhibition of NF- kappa B-Associated Nitric Oxide and Prostaglandin E2
      production.
AB  - Erigeron annuus is a naturalized plant belonging to Compositae (asteraceae)
      family, which is called the annual fleabane, and commonly found at meadows and
      roadside. This study investigated the anti-inflammatory effects of the extract of
      E. annuus roots (EER), as assessed by the paw edema formation and histological
      analysis in rat, and the productions of nitric oxide (NO), prostaglandin E2
      (PGE2), and pro-inflammatory cytokines in Raw264.7 murine macrophages.
      Carrageenan treatment promoted infiltration of inflammatory cells and caused
      swelling in the hind paw. Oral administrations of EER (0.3 g/kg and 1 g/kg)
      attenuated acute inflammation similar to the result using dexamethasone (1
      mg/kg). Treatment of macrophages with lipopolysaccharide (LPS) simulated
      inflammatory condition: LPS significantly increased the productions of NO, PGE2,
      and proinflammatory cytokines. EER suppressed activation of macrophages,
      preventing the induction of iNOS and COX-2 protein expressions. LPS treatment
      induced phosphorylation of I- kappa B alpha and increased the level of nuclear NF
      kappa B protein, both of which were suppressed by concomitant treatment of EER.
      In conclusion, EER ameliorated acute inflammation in rats, and the induction of
      NO, PGE2, and proinflammatory cytokines in Raw264.7 cells. EER's effects may be
      associated with its inhibition of NF- kappa B activation, suggesting its effect
      on inflammatory diseases.

PMID- 23533474
TI  - Quercetin Preserves beta -Cell Mass and Function in Fructose-Induced
      Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation.
AB  - Fructose-induced hyperinsulinemia is associated with insulin compensative
      secretion and predicts the onset of type 2 diabetes. In this study, we
      investigated the preservation of dietary flavonoid quercetin on pancreatic beta 
      cell mass and function in fructose-treated rats and INS-1 beta -cells. Quercetin
      was confirmed to reduce serum insulin and leptin levels and blockade islet
      hyperplasia in fructose-fed rats. It also prevented fructose-induced beta -cell
      proliferation and insulin hypersecretion in INS-1 beta -cells. High fructose
      increased forkhead box protein O1 (FoxO1) expressions in vivo and in vitro, which
      were reversed by quercetin. Quercetin downregulated Akt and FoxO1 phosphorylation
      in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose
      treated INS-1 beta -cells. The elevated Akt phosphorylation in fructose-treated
      INS-1 beta -cells was also restored by quercetin. Additionally, quercetin
      suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and
      insulin gene (Ins1 and Ins2) in vivo and in vitro. In fructose-treated INS-1 beta
      -cells, quercetin elevated the reduced janus kinase 2/signal transducers and
      activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the
      increased suppressor of cytokine signaling 3 (Socs3) expression. These results
      demonstrate that quercetin protects beta -cell mass and function under high
      fructose induction through improving leptin signaling and preserving pancreatic
      Akt/FoxO1 activation.

PMID- 23533475
TI  - Antrodia camphorata Grown on Germinated Brown Rice Suppresses Melanoma Cell
      Proliferation by Inducing Apoptosis and Cell Differentiation and Tumor Growth.
AB  - Antrodia camphorata grown on germinated brown rice (CBR) was prepared to suppress
      melanoma development. CBR extracts were divided into hexane, EtOAc, BuOH, and
      water fractions. Among all the fractions, EtOAc fraction showed the best
      suppressive effect on B16F10 melanoma cell proliferation by CCK-8 assay. It also
      showed the increased cell death and the changed cellular morphology after CBR
      treatment. Annexin V-FITC/PI, flow cytometry, and western blotting were performed
      to elucidate anticancer activity of CBR. The results showed that CBR induced p53
      mediated apoptotic cell death of B16F10. CBR EtOAc treatment increased melanin
      content and melanogenesis-related proteins of MITF and TRP-1 expressions, which
      supports its anticancer activity. Its potential as an anticancer agent was
      further investigated in tumor-xenografted mouse model. In melanoma-xenografted
      mouse model, melanoma tumor growth was significantly suppressed under CBR EtOAc
      fraction treatment. HPLC analysis of CBR extract showed peak of adenosine. In
      conclusion, CBR extracts notably inhibited B16F10 melanoma cell proliferation
      through the p53-mediated apoptosis induction and increased melanogenesis. These
      findings suggest that CBR EtOAc fraction can act as an effective anticancer agent
      to treat melanoma.

PMID- 23533476
TI  - Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in
      C57BL/6 Mice via the Inhibition of the PPARgamma Pathway.
AB  - Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine,
      wax gourd peel is used to prevent and treat metabolic diseases such as
      hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However,
      there is no experimental evidence to support these applications. Here, we
      examined the effect of the extract of wax gourd peel (EWGP) on metabolic
      disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP
      blocked body weight gain and lowered serum total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood
      glucose in mice fed with a high-fat diet. In the therapeutic study, we induced
      obesity in the mice and treated with EWGP for two weeks. We found that EWGP
      treatment reduced serum and liver triglyceride (TG) contents and fasting blood
      glucose and improved glucose tolerance in the mice. Reporter assay and gene
      expression analysis showed that EWGP could inhibit peroxisome proliferator
      activated receptor gamma (PPAR gamma ) transactivities and could decrease mRNA
      levels of PPAR gamma and its target genes. We also found that HMG-CoA reductase
      (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP
      lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition
      of PPAR gamma and HMGCR signaling.

PMID- 23533478
TI  - Hepatoprotective effects of a chinese herbal formula, longyin decoction, on
      carbon-tetrachloride-induced liver injury in chickens.
AB  - The objective of this study is to establish poultry liver injury model induced by
      (CCl4) and seek effective hepatoprotective herbals for clinical application.
      Different doses of CCl4 dissolved in vegetable oil (1 : 1, V/V) were injected via
      pectoral muscle to induce acute liver injury model in chickens. An herbal
      formula, Longyin decoction, was prepared for hepatoprotection test on chicken
      acute liver injury models. The pathologic changes of the liver were observed, and
      the activities of ALT and AST were, respectively, detected to evaluate the
      hepatoprotective effects of Longyin decoction on chickens. The chicken acute
      liver injury model was successfully established by injecting CCl4 via pectoral
      muscle. The best dose of CCl4 inducing chicken liver injury was 4.0 mL/kg.BW
      (body weight). The results of qualitative determination by HPTLC showed that the
      components of Longyin decoction contained Gentian, Capillaries, Gardenia, and
      Bupleurum root. In the high-dose Longyin group and the middle-dose Longyin group,
      the pathological changes of the damaged liver were mitigated and the activities
      of ALT and AST in serum were reduced significantly. Longyin decoction has obvious
      hepatoprotective effect on acute liver injury induced by CCl4.

PMID- 23533477
TI  - Botulinum toxin for the treatment of myofascial pain syndromes involving the neck
      and back: a review from a clinical perspective.
AB  - Introduction. Botulinum toxin inhibits acetylcholine (ACh) release and probably
      blocks some nociceptive neurotransmitters. It has been suggested that the
      development of myofascial trigger points (MTrP) is related to an excess release
      of ACh to increase the number of sensitized nociceptors. Although the use of
      botulinum toxin to treat myofascial pain syndrome (MPS) has been investigated in
      many clinical trials, the results are contradictory. The objective of this paper
      is to identify sources of variability that could explain these differences in the
      results. Material and Methods. We performed a content analysis of the clinical
      trials and systematic reviews of MPS. Results and Discussion. Sources of
      differences in studies were found in the diagnostic and selection criteria, the
      muscles injected, the injection technique, the number of trigger points injected,
      the dosage of botulinum toxin used, treatments for control group, outcome
      measures, and duration of followup. The contradictory results regarding the
      efficacy of botulinum toxin A in MPS associated with neck and back pain do not
      allow this treatment to be recommended or rejected. There is evidence that
      botulinum toxin could be useful in specific myofascial regions such as piriformis
      syndrome. It could also be useful in patients with refractory MPS that has not
      responded to other myofascial injection therapies.

PMID- 23533479
TI  - The Herbal Drug Melampyrum pratense L. (Koch): Isolation and Identification of
      Its Bioactive Compounds Targeting Mediators of Inflammation.
AB  - Melampyrum pratense L. (Koch) is used in traditional Austrian medicine for the
      treatment of different inflammation-related conditions. In this work, we show
      that the extracts of M. pratense stimulated peroxisome proliferator-activated
      receptors- (PPARs-) alpha and - gamma that are well recognized for their anti
      inflammatory activities. Furthermore, the extract inhibited the activation of the
      proinflammatory transcription factor NF- kappa B and induction of its target
      genes interleukin-8 (IL-8) and E-selectin in vitro. Bioassay-guided fractionation
      identified several active flavonoids and iridoids including melampyroside and
      mussaenoside and the phenolic compound lunularin that were identified in this
      species for the first time. The flavonoids apigenin and luteolin were
      distinguished as the main components accountable for the anti-inflammatory
      properties. Apigenin and luteolin effectively inhibited tumor necrosis factor
      alpha (TNF- alpha )-induced NF- kappa B-mediated transactivation of a luciferase
      reporter gene. Furthermore, the two compounds dose-dependently reduced IL-8 and E
      selectin protein expression after stimulation with lipopolysaccharide (LPS) or
      TNF- alpha in endothelial cells (ECs). The iridoids melampyroside and
      mussaenoside prevented the elevation of E-selectin in LPS-stimulated ECs.
      Lunularin was found to reduce the protein levels of the proinflammatory mediators
      E-selectin and IL-8 in ECs in response to LPS. These data validate the
      ethnomedical use of M. pratense for the treatment of inflammatory conditions and
      point to the constituents accountable for its anti-inflammatory activity.

PMID- 23533480
TI  - Integrating traditional chinese medicine services in community health centers:
      insights into utilization patterns in the pearl river region of china.
AB  - In China's healthcare reform, community health centers (CHCs) are designed to
      take a pivotal role in providing primary care. Whilst about 20% of all outpatient
      care in China is delivered by the traditional Chinese medicine (TCM) sector,
      hospitals, instead of CHCs, are major providers. Using current patterns of
      patient utilization this study aims to inform CHCs on how they may strengthen
      access to TCM services. Three thousand three hundred and sixty CHC patients from
      six cities within the urban Pearl Delta Region were enumerated using multistage
      cluster sampling. Fifty-two percent had visited herbalists within three months
      with a mean visit frequency of 1.50 times. Herbal treatments, which are cheaper
      than western medicines, were more popular amongst those who needed to pay out of
      pocket including the uninsured. Herbal medicines appeared to be an alternative
      for those who are underinsured. Acupuncturists and massage therapists were
      visited by smaller proportions, 6.58% and 5.98%, respectively, with a mean three
      month visit of 0.27 and 0.26 times. Access was restricted by lack of social
      insurance coverage. Whilst increasing provision of TCM in CHCs might respond to
      patient demand, increasing insurance coverage for TCM needs to be evaluated using
      current evidence on safety and effectiveness.

PMID- 23533481
TI  - The Possible Neuronal Mechanism of Acupuncture: Morphological Evidence of the
      Neuronal Connection between Groin A-Shi Point and Uterus.
AB  - Somatovisceral reflex suggested that the somatic stimulation could affect
      visceral function like acupuncture which treats diseases by stimulating
      acupoints. The neuronal connection between somatic point and visceral organ was
      not clear. Uterine pain referred to the groin region has long been recognized
      clinically. Wesselmann, using neurogenic plasma extravasation method, showed that
      uterine pain was referred to the groin region through a neuronal mechanism
      (Wesselmann and Lai 1997). This connection could be considered through the
      somatovisceral reflex pathway. However, the relay center of this pathway is still
      not clearly identified. In the present study, bee venom was injected in the groin
      region to induce central Fos expression to map the sensory innervation of groin
      region. Pseudorabies virus (PrV), a transneuronal tracer, was injected in the
      uterus to identify the higher motor control of the uterus. Immunohistochemistry
      staining revealed the Fos expression and PrV-infected double-labeled neurons in
      the nucleus of solitary tract (NTS), the dorsal motor nucleus of vagus (DMX), and
      the paraventricular hypothalamic nucleus (PVN). These results suggest a
      somatoparasympathetic neuronal connection (groin-spinal dorsal horn-NTS/DMX
      uterus) and a somatosympathetic neuronal connection (groin-spinal dorsal horn-NTS
      PVN-uterus). These two neuronal connections could be the prerequisites to the
      neuronal basis of the somatovisceral reflex and also the neuronal mechanism of
      acupuncture.

PMID- 23533482
TI  - 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human
      Tumor Cells via Regulation of Apoptosis-Related Proteins.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      candidate for the treatment of cancer, because it preferentially induces
      apoptosis in numerous cancer cells with little or no effect on normal cells. 5,7
      Dihydroxyflavone is a dietary flavonoid commonly found in many plants. Here we
      show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic
      concentrations induced strong apoptotic response in human hepatocarcinoma HepG2
      cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells. We
      further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL
      induced apoptosis in HepG2 cells. 5,7-Dihydroxyflavone up-regulated the
      expression of pro-apoptotic protein Bax, attenuated the expression of anti
      apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels
      of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the
      process of apoptosis. Moreover, 5,7-dihydroxyflavone and TRAIL were well
      tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced
      tumor burden in vivo in a HepG2 tumor xenograft model. Interestingly, 5,7
      dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not
      observed in normal human hepatocytes L-O2. These results suggest that the 5,7
      dihydroxyflavone in combination with TRAIL might be used for cancer prevention
      and/or therapy.

PMID- 23533483
TI  - 4-Hydroxy-17-methylincisterol from Agaricus blazei Decreased Cytokine Production
      and Cell Proliferation in Human Peripheral Blood Mononuclear Cells via Inhibition
      of NF-AT and NF-kappaB Activation.
AB  - Agaricus blazei Murill is an edible and medicinal mushroom. In the previous
      study, we have proved that extracts of A. blazei inhibit human peripheral blood
      mononuclear cell (PBMC) proliferation activated with phytohemagglutinin (PHA).
      Currently, we purified 4-hydroxy-17-methylincisterol (4-HM; C21H33O3) from A.
      blazei investigated its regulatory effects on cytokine productions and cell
      proliferation of PBMC induced by PHA. The results indicated that 4-HM suppressed,
      in activated PBMC, the production and mRNA expression of interleukin-2 (IL-2), IL
      4, tumor necrosis factor- alpha , and interferon- gamma in a concentration
      dependent manner. This inhibition was not related to cell viability. While 4-HM
      did not affect ERK phosphorylation and its downstream c-fos gene expression in
      PBMC induced by PHA, it decreased both NF-AT and NF- kappa B activation. The
      upstream signaling of NF-AT and NF- kappa B, intracellular calcium concentrations
      ([Ca(2+)]i), and protein kinase C theta (PKC theta ) activation in PHA-treated
      PBMC were reduced by 4-HM. The data demonstrated that the suppressant effects of
      4-HM on cell proliferation in PBMC activated by PHA appeared to be mediated, at
      least in part, through inhibition of Ca(2+) mobilization and PKC theta
      activation, NF-AT and NF- kappa B activation, and cytokine transcripts and
      productions of PBMC. We suggested that A. blazei contained a potential
      immunomodulator 4-HM.

PMID- 23533484
TI  - Metabolomic study of collagen-induced arthritis in rats and the interventional
      effects of huang-lian-jie-du-tang, a traditional chinese medicine.
AB  - Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine (TCM) with anti
      inflammatory activity. The present study used a metabolomic approach based on LC
      Q-TOF-MS to profile rheumatoid-arthritis- (RA-) related metabolic changes and to
      investigate the interventional mechanisms of HLJDT in collagen-induced arthritis
      rats. Forty male Wistar rats were randomly divided into five groups: (1) a model
      group, (2) a normal control group, (3) a dexamethasone group, (4) a HLJDT group,
      and (5) a group that received 13 components of HLJDT. Plasma samples were
      collected 8, 15, and 22 days after the rats were injected with bovine type II
      collagen. By combining variable importance in the projection values with partial
      least squares discriminant analysis, 18 potential biomarkers were identified in
      the plasma samples. The biomarkers were primarily involved in glycerophospholipid
      metabolism, fatty acid metabolism, tryptophan metabolism, linoleic acid
      metabolism, phenylalanine metabolism, purine metabolism, arachidonic acid
      metabolism, and bile acid biosynthesis. Using the potential biomarkers as a
      screening index, the results suggest that HLJDT can potentially reverse the
      process of RA by partially regulating fatty acid oxidation and arachidonic acid
      metabolism. This study demonstrates that a metabolomic strategy is useful for
      identifying potential RA biomarkers and investigating the underlying mechanisms
      of a TCM in RA treatment.

PMID- 23533485
TI  - Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on
      Cultured Human Cancer Cell Lines.
AB  - Clinacanthus nutans Lindau leaves (CN) have been used in traditional medicine but
      the therapeutic potential has not been explored for cancer prevention and
      treatment. Current study aimed to evaluate the antioxidant and antiproliferative
      effects of CN, extracted in chloroform, methanol, and water, on cancer cell
      lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric
      oxide, and hydrogen peroxide based radical scavenging assays, whereas the
      tumoricidal effect was tested on HepG2, IMR32, NCL-H23, SNU-1, Hela, LS-174T,
      K562, Raji, and IMR32 cancer cells using MTT assay. Our data showed that CN in
      chloroform extract was a good antioxidant against DPPH and galvinoxyl radicals,
      but less effective in negating nitric oxide and hydrogen peroxide radicals.
      Chloroform extract exerted the highest antiproliferative effect on K-562 (91.28
      +/- 0.03%) and Raji cell lines (88.97 +/- 1.07%) at 100  MU g/ml and the other
      five cancer cell lines in a concentration-dependent manner, but not on IMR-32
      cells. Fourteen known compounds were identified in chloroform extract, which was
      analysed by gas chromatography-mass spectra analysis. In conclusion, CN extracts
      possess antioxidant and antiproliferative properties against cultured cancer cell
      lines, suggesting an alternate adjunctive regimen for cancer prevention or
      treatment.

PMID- 23533486
TI  - Aqueous Extract of Paeonia lactiflora and Paeoniflorin as Aggregation Reducers
      Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3.
AB  - Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 as well as Huntington's
      disease are a group of neurodegenerative disorders caused by expanded CAG repeats
      encoding a long polyglutamine (polyQ) tract in the respective proteins. Evidence
      has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ
      proteins leads to apoptosis and cell death. Thus suppression of aggregate
      formation is expected to inhibit a wide range of downstream pathogenic events in
      polyQ diseases. In this study, we established a high-throughput aggregation
      screening system using 293 ATXN3/Q75-GFP cells and applied this system to test
      the aqueous extract of Paeonia lactiflora (P. lactiflora) and its constituents.
      We found that the aggregation can be significantly prohibited by P. lactiflora
      and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin
      upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them
      further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP
      cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to
      work on polyQ-aggregation reduction and provide insight into the possible working
      mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting
      point for screening more potential herbs for the treatment of SCA3 and other
      polyQ diseases.

PMID- 23533487
TI  - QiShenYiQi Pills, a Compound Chinese Medicine, Ameliorates Doxorubicin-Induced
      Myocardial Structure Damage and Cardiac Dysfunction in Rats.
AB  - QiShenYiQi Pills (QSYQ) is a compound Chinese medicine used for treatment of
      cardiovascular diseases. The present study investigated the effects of QSYQ on
      the Doxorubicin- (DOX-) induced disorders in rat cardiac structure and function
      and the possible mechanism underlying. A total of 24 male Sprague-Dawley rats
      were administrated by intraperitoneal injections with DOX at a dose of 2.5 mg/kg,
      once every day for a total of 6 times. After the 6th injection, the rats were
      evaluated by echocardiographic analysis, and the animals with injured heart (n =
      14) were divided into 2 groups and further treated with (n = 7) or without (n =
      7) QSYQ by gavage at a dose of 0.2 g/day, once a day, over the next 2 weeks. Two
      weeks after QSYQ treatment, the following variables were assessed: myocardial
      blood flow (MBF) by Laser-Doppler Perfusion Imager, the ratio of heart weight to
      body weight (HW/BW), myocardial histology, myocardial content of ATP, AMP, free
      fatty acids (FFAs) and AMP/ATP by ELISA, and expression of PPAR alpha , PGC-1
      alpha , and ATP 5D by Western blot. Statistical analysis was performed using one
      way ANOVA followed by Turkey test for multiple comparisons. DOX challenge
      significantly increased left ventricular internal diameter and HW/BW and
      decreased the thickness of the left ventricular posterior wall, the left
      ventricle ejection fraction, and the left ventricle fractional shortening. DOX
      also increased AMP, FFA, and AMP/ATP, decreased ATP, and downregulated the
      protein content of ATP 5D, PPAR alpha , and PGC-1 alpha . All these DOX-induced
      cardiac insults were attenuated significantly by QSYQ treatment. These results
      show the potential of QSYQ to ameliorate DOX-induced disorders in cardiac
      structure and function; this effect may be related to the increase in myocardial
      ATP content via the upregulation of ATP 5D, PPAR alpha , and PGC-1 alpha and the
      oxidation of FFA.

PMID- 23533488
TI  - A Methanol Extract of Brugmansia arborea Affects the Reinforcing and Motor
      Effects of Morphine and Cocaine in Mice.
AB  - Previous reports have shown that several of the effects of morphine, including
      the development of tolerance and physical withdrawal symptoms, are reduced by
      extracts of Brugmansia arborea (L.) Lagerheim (Solanaceae) (B. arborea). In the
      present study we evaluate the action of the methanol extract of B. arborea (7.5
      60 mg/kg) on the motor and reinforcing effects of morphine (20 and 40 mg/kg) and
      cocaine (25 mg/kg) using the conditioned place preference (CPP) procedure. At the
      doses employed, B. arborea did not affect motor activity or induce any effect on
      CPP. The extract partially counteracted morphine-induced motor activity and
      completely blocked the CPP induced by 20 mg/kg morphine. On the other hand, B.
      arborea blocked cocaine-induced hyperactivity but did not block cocaine-induced
      CPP. Reinstatement of extinguished preference with a priming dose of morphine or
      cocaine was also inhibited by B. arborea. The complex mechanism of action of B.
      arborea, which affects the dopaminergic and the cholinergic systems, seems to
      provide a neurobiological substrate for the effects observed. Considered as a
      whole, these results point to B. arborea as a useful tool for the treatment of
      morphine or cocaine abuse.

PMID- 23533489
TI  - Acupuncture or Acupressure at the Sanyinjiao (SP6) Acupoint for the Treatment of
      Primary Dysmenorrhea: A Meta-Analysis.
AB  - This meta-analysis aimed to evaluate the effectiveness of acupuncture or
      acupressure at the Sanyinjiao (SP6) acupoint in relieving pain associated with
      primary dysmenorrhea. We searched the scientific literature databases to identify
      randomized controlled trials. The primary outcome was visual analogue scale (VAS)
      pain score. Three acupuncture and four acupressure trials were included in the
      meta-analyses. For the acupuncture analysis, there was no difference in the mean
      VAS score reduction between the SP6 acupoint and control (GB39 acupoint) groups (
      4.935; lower limit = -15.757, upper limit = 5.887; P = 0.371). For the
      acupressure analysis, there was a significant difference in the mean VAS score
      after intervention between the SP6 acupoint and control (rest/light touch at
      SP6/nonacupoint acupressure) groups, favoring the SP6 acupoint group (-1.011;
      lower limit = -1.622, upper limit = -0.400; P = 0.001). Sensitivity analyses
      demonstrated good reliability of the meta-analyses findings. These findings
      suggest that acupuncture at SP6 is not more effective than acupuncture at an
      unrelated acupoint in the relief from primary dysmenorrhea. Acupressure at SP6
      may be effective in the relief from primary dysmenorrhea. High-quality randomized
      controlled trials are needed to confirm these findings.

PMID- 23533490
TI  - 6-Shogaol Protects against Oxidized LDL-Induced Endothelial Injruries by
      Inhibiting Oxidized LDL-Evoked LOX-1 Signaling.
AB  - Endothelial dysfunction and oxLDL are believed to be early and critical events in
      atherogenesis. 6-Shogaol is the major bioactive compound present in Zingiber
      officinale and possesses the anti-atherosclerotic effect. However, the mechanisms
      remain poorly understood. The goal of this study was to investigate the effects
      of 6-shogaol on oxLDL-induced Human umbilical vein endothelial cells (HUVECs)
      injuries and its possible molecular mechanisms. Hence, we studied the effects of
      6-shogaol on cell apoptosis, cellular reactive oxygen species (ROS), NF- kappa B
      activation, Bcl-2 expression, and caspase -3, -8, -9 activities. In addition, E
      selectin, MCP-1, and ICAM-1 were determined by ELISA. Our study show that oxLDL
      increased LOX-1 expression, ROS levels, NF- kappa B, caspases-9 and -3 activation
      and decreased Bcl-2 expression in HUVECs. These alterations were attenuated by 6
      shogaol. Cotreatment with 6-shogaol and siRNA of LOX-1 synergistically reduced
      oxLDL-induced caspases -9, -3 activities and cell apoptosis. Overexpression of
      LOX-1 attenuated the protection by 6-shogaol and suppressed the effects of 6
      shogaol on oxLDL-induced oxidative stress. In addition, oxLDL enhanced the
      activation of NF- kappa B and expression of adhesion molecules. Pretreatment with
      6-shogaol, however, exerted significant cytoprotective effects in all events. Our
      data indicate that 6-shogaol might be a potential natural antiapoptotic agent for
      the treatment of atherosclerosis.

PMID- 23533491
TI  - Optimization on preparation condition of propolis flavonoids liposome by response
      surface methodology and research of its immunoenhancement activity.
AB  - The aim of this study is to prepare propolis flavonoids liposome (PFL) and
      optimize the preparation condition and to investigate further whether liposome
      could promote the immunoenhancement activity of propolis flavonoids (PF). PFL was
      prepared with ethanol injection method, and the preparation conditions of PFL
      were optimized with response surface methodology (RSM). Moreover, the
      immunoenhancement activity of PFL and PF in vitro was determined. The result
      showed that the optimal preparation conditions for PFL by response surface
      methodology were as follows: ratio of lipid to drug (w/w) 9.6 : 1, ratio of
      soybean phospholipid to cholesterol (w/w) 8.5 : 1, and speed of injection 0.8
      mL.min(-1). Under these conditions, the experimental encapsulation efficiency of
      PFL was 91.67 +/- 0.21%, which was close to the predicted value. Therefore, the
      optimized preparation condition is very reliable. Moreover, the results indicated
      that PFL could not only significantly promote lymphocytes proliferation singly or
      synergistically with PHA, but also increase expression level of IL-2 and IFN
      gamma mRNA. These indicated that liposome could significantly improve the
      immunoenhancement activity of PF. PFL demonstrates the significant
      immunoenhancement activity, which provides the theoretical basis for the further
      experiment in vivo.

PMID- 23533492
TI  - Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's
      disease model.
AB  - Gastrodia elata (GE) Blume is one of the most important traditional plants in
      Oriental countries and has been used for centuries to improve various conditions.
      The phenolic glucoside gastrodin is an active constituent of GE. The aim of this
      study was to investigate the neuroprotective role of gastrodin in 1-methyl-4
      phenylpyridinium (MPP(+))/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP)
      induced human dopaminergic SH-SY5Y cells and mouse model of Parkinson's disease
      (PD), respectively. Gastrodin significantly and dose dependently protected
      dopaminergic neurons against neurotoxicity through regulating free radicals,
      Bax/Bcl-2 mRNA, caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) in SH
      SY5Y cells stressed with MPP(+). Gastrodin also showed neuroprotective effects in
      the subchronic MPTP mouse PD model by ameliorating bradykinesia and motor
      impairment in the pole and rotarod tests, respectively. Consistent with this
      finding, gastrodin prevented dopamine depletion and reduced reactive astrogliosis
      caused by MPTP as assessed by immunohistochemistry and immunoblotting in the
      substantiae nigrae and striatata of mice. Moreover, gastrodin was also effective
      in preventing neuronal apoptosis by attenuating antioxidant and antiapoptotic
      activities in these brain areas. These results strongly suggest that gastrodin
      has protective effects in experimental PD models and that it may be developed as
      a clinical candidate to ameliorate PD symptoms.

PMID- 23533493
TI  - Is yangxue qingnao granule combined with antihypertensive drugs, a new
      integrative medicine therapy, more effective than antihypertensive therapy alone
      in treating essential hypertension?
AB  - Background. Yangxue Qingnao granule (YQG) combined with antihypertensive drugs, a
      new integrative medicine therapy, has been widely used for essential hypertension
      (EH) in China. This study aims to assess the current clinical evidence of YQG
      combined with antihypertensive drugs for EH. Methods. Randomized controlled
      trials(RCTs) published between 1996 and 2012 on YQG combined with
      antihypertensive drugs versus antihypertensive drugs in treating EH were
      retrieved from six major electronic databases, including The Cochrane Library,
      PubMed, Chinese National Knowledge Infrastructure, Chinese Scientific Journal
      Database, Chinese Biomedical Literature Database, and Wanfang Data. Meta-analysis
      was performed on the overall effects on blood pressure. Results. Twelve
      randomized trials were included. Methodological quality of the trials was
      evaluated as generally low. Meta-analysis showed that YQG combined with
      antihypertensive drugs demonstrated potential effect for lowing either SBP (MD: 
      7.31 [-11.75, -2.87]; P = 0.001) or DBP (MD: -5.21 [-8.19, -2.24]; P = 0.0006)
      compared to antihypertensive drugs alone. Conclusions. It indicated that YQG
      combined with antihypertensive drugs is more effective than antihypertensive
      drugs alone in treating EH. However, more RCTs of larger scale,
      multicentre/country, longer follow-up periods, and higher quality are required to
      verify the efficacy of integrative medicine therapy over all antihypertensive
      therapies.

PMID- 23533494
TI  - Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in
      human acute myeloid leukemia.
AB  - IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the
      growth of cancer stem cells (CSCs). Resveratrol, an important integrant in
      traditional Chinese medicine, possesses certain antitumor effects. However, the
      mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study
      first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1
      beta in AML patients were higher and lower, respectively, than healthy donors.
      The expression of Shh preproproteins, and C- and N-terminal Shh peptides
      increased in bone marrow and peripheral blood mononuclear cells isolated from AML
      patients, and the plasma N-Shh secretion was greater. To further clarify the
      effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were
      tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an
      increase of cell viability. Resveratrol significantly decreased CSC-related Shh
      expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60
      cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting
      cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh
      signaling, and this effect might be blocked by resveratrol. Further
      investigations of Shh as a prognostic marker and resveratrol as a therapeutic
      drug target to CSCs in AML are surely warranted.

PMID- 23533495
TI  - Anacardic acids from cashew nuts ameliorate lung damage induced by exposure to
      diesel exhaust particles in mice.
AB  - Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have
      antimicrobial and antioxidant activities and modulate immune responses and
      angiogenesis. As inflammatory lung diseases have been correlated to environmental
      pollutants exposure and no reports addressing the effects of dietary
      supplementation with anacardic acids on lung inflammation in vivo have been
      evidenced, we investigated the effects of supplementation with anacardic acids in
      a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice
      received an intranasal instillation of 50  MU g of DEP for 20 days. Ten days
      prior to DEP instillation, animals were pretreated orally with 50, 150, or 250
      mg/kg of anacardic acids or vehicle (100  MU L of cashew nut oil) for 30 days.
      The biomarkers of inflammatory and antioxidant responses in the alveolar
      parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were
      investigated. All doses of anacardic acids ameliorated antioxidant enzyme
      activities and decreased vascular adhesion molecule in vessels. Animals that
      received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and
      tumor necrosis factor in the lungs and BALF, respectively. In summary, we
      demonstrated that AAs supplementation has a potential protective role on
      oxidative and inflammatory mechanisms in the lungs.

PMID- 23533496
TI  - Improvement of circadian rhythm of heart rate variability by eurythmy therapy
      training.
AB  - Background. Impairment of circadian rhythm is associated with various clinical
      problems. It not only has a negative impact on quality of life but can also be
      associated with a significantly poorer prognosis. Eurythmy therapy (EYT) is an
      anthroposophic movement therapy aimed at reducing fatigue symptoms and stress
      levels. Objective. This analysis of healthy subjects was conducted to examine
      whether the improvement in fatigue symptoms was accompanied by improvements in
      the circadian rhythm of heart rate variability (HRV). Design. Twenty-three women
      performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs) were recorded
      before and after the EYT trial. HRV was quantified by parameters of the frequency
      and time domains and the nonlinear parameters of symbolic dynamics. Results. The
      day-night contrast with predominance of vagal activity at night becomes more
      pronounced after the EYT training, and with decreased Ultralow and very low
      frequencies, the HRV shows evidence of calmer sleep. During the night, the
      complexity of the HRV is significantly increased indicated by nonlinear
      parameters. Conclusion. The analysis of the circadian patterns of
      cardiophysiological parameters before and after EYT shows significant
      improvements in HRV in terms of greater day-night contrast caused by an increase
      of vagal activity and calmer and more complex HRV patterns during sleep.

PMID- 23533497
TI  - Application of Scutellariae radix, Gardeniae fructus, and Probiotics to Prevent
      Salmonella enterica Serovar Choleraesuis Infection in Swine.
AB  - Salmonella enterica serovar Choleraesuis, a host-adapted pathogen of swine,
      usually causes septicemia. Lactic acid bacteria (LAB) strains have been widely
      studied in recent years for their probiotic properties. In this study, a mouse
      infection model first screened for potential agents against infection, then a pig
      infection model evaluated effects of LAB strains and herbal plants against
      infection. Scutellariae radix (SR) and Gardeniae fructus (GF) showed abilities to
      reduce bacteria shedding and suppressing serum level of TNF- alpha induced by
      infection in swine. Bioactivities of SR and GF were enhanced by combining with
      LAB strains, which alone could speed up the bacteria elimination time in feces
      and boost immunity of infected pigs. Baicalein and genipin exhibited stronger
      cytotoxicity than baicalin and geniposide did, as well as prevent Salmonella from
      invading macrophages. Our study suggests LAB strains as exhibiting multiple
      functions: preventing infection, enhancing immunity to prepare host defenses
      against further infection, and adjusting intestinal microbes' enzymatic activity
      in order to convert herbal compounds to active compounds. The SR/GF-LAB strain
      mixture holds potential infection-prevention agents supplied as feed additives.

PMID- 23533498
TI  - Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi
      Sidr Honey in Rats.
AB  - The present study was undertaken to investigate the possible protective effect of
      Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress
      and liver and kidney damage in rat. Moreover, the antioxidant activity and the
      phenolic and flavonoidal contents were determined. The hepatorenal protective
      activity of the SSH was determined by assessing biochemical, hematological, and
      histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin
      urea, uric acid, and MDA level in liver and kidney tissues were significantly
      elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and
      total protein levels in liver and kidney were declined significantly in CCl4
      alone treated animals. Pretreatment with SSH and silymarin prior to the
      administration of CCl4 significantly prevented the increase of the serum levels
      of enzyme markers and reduced oxidative stress. SSH also exhibited a significant
      lipid-lowering effect and caused an HDL-C enhanced level in serum. The
      histopathological evaluation of the liver and kidney also revealed that honey
      protected incidence of both liver and kidney lesions. Moreover, SSH showed a
      strong antioxidant activity in DPPH and beta -carotene-linoleic acid assays. SSH
      was found to contain phenolic compounds. Additionally, the SSH supplementation
      restored the hepatocytes viability against 2',7'-dichlorofluorescein (DCF)
      toxicity in ex vivo test.

PMID- 23533499
TI  - Medicinal Fungus Antrodia cinnamomea Inhibits Growth and Cancer Stem Cell
      Characteristics of Hepatocellular Carcinoma.
AB  - Background. Antrodia cinnamomea is an edible fungus commonly used in Asia as a
      well-known medicinal herb capable of treating drug intoxication and liver cancer.
      Methods. This study evaluated the anticancer activity of its biotechnological
      product, mycelial fermentation broth (AC-MFB) on hepatocellular carcinoma (HCC)
      by tetrazolium-based colorimetric assay in vitro and syngeneic Balb/c 1MEA.7R.1
      tumor implantation model in vivo. Given that cancer stem cell characteristics,
      such as angiogenesis, invasiveness, and migration, are known to cause recurrence,
      we further evaluated the effect of AC-MFB on cellular viability inhibition of HCC
      cells, angiogenic activity and migration of endothelial cells, and the release of
      proangiogenic factors from HCC cells. Results. We found that AC-MFB markedly
      inhibited the growth of HCC without hepatic enzyme abnormality. This anti-HCC
      activity was validated by growth-inhibitory effects on both cultured murine
      1MEA.7R.1 and human HA22T/VGH HCC cells. For cancer stem cell characteristics, AC
      MFB inhibited the cellular viability, migration, and tube formation activity of
      EA. hy926 and SVEC4-10 endothelial cells. Production of extracellular vascular
      endothelial growth factor and intracellular hypoxia-inducible factor-1 alpha from
      HCC cells was suppressed by AC-MFB. Conclusion. Antrodia cinnamomea could inhibit
      the growth and cancer stem cell characteristics of HCC cells.

PMID- 23533500
TI  - Improvement of liquid fructose-induced adipose tissue insulin resistance by
      ginger treatment in rats is associated with suppression of adipose macrophage
      related proinflammatory cytokines.
AB  - Adipose tissue insulin resistance (Adipo-IR) results in excessive release of free
      fatty acids from adipose tissue, which plays a key role in the development of
      "lipotoxicity." Therefore, amelioration of Adipo-IR may benefit the treatment of
      other metabolic abnormalities. Here we found that treatment with the alcoholic
      extract of ginger (50 mg/kg/day, by oral gavage) for five weeks attenuated liquid
      fructose-induced hyperinsulinemia and an increase in the homeostasis model
      assessment of insulin resistance (HOMA-IR) index in rats. More importantly,
      ginger reversed the increases in the Adipo-IR index and plasma nonesterified
      fatty acid concentrations during the oral glucose tolerance test assessment.
      Adipose gene/protein expression profiles revealed that ginger treatment
      suppressed CD68 and F4/80, two important macrophage accumulation markers.
      Consistently, the macrophage-associated cytokines tissue necrosis factor alpha
      and interleukin-6 were also downregulated. In contrast, insulin receptor
      substrate (IRS)-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic
      protein (MCP)-1 and its receptor chemokine (C-C motif) receptor-2 were also
      suppressed. Thus these results suggest that amelioration of fructose-induced
      Adipo-IR by ginger treatment in rats is associated with suppression of adipose
      macrophage-related proinflammatory cytokines.

PMID- 23533501
TI  - The preventive effect of biochanin a on bone loss in ovariectomized rats:
      involvement in regulation of growth and activity of osteoblasts and osteoclasts.
AB  - Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium
      pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX)
      animal model has never been clarified. The objective of this study was to
      investigate the biological effects of BCA on bone loss in OVX rats in vivo and on
      the development of osteoblasts and osteoclasts in vitro. Ovariectomy resulted in
      a marked increase in body weight and a decrease in femoral bone mineral density
      and trabecular bone volume that was prevented by BCA or 17 beta -estradiol (E2)
      treatment. However, an increase in uterine weight was observed in E2-treated OVX
      rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA
      expression of osterix, collagen type I, alkaline phosphatase (ALP), and
      osteocalcin and decreased the mRNA expression of tartrate-resistant acid
      phosphatase (TRAP) and the receptor activator of nuclear factor- kappa B ligand
      (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA
      or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and
      serum tumor necrosis factor alpha (TNF- alpha ) and interleukin-1 beta (IL-1 beta
      ). In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and
      increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast
      proliferation and decreased osteoclast bone resorption. These findings suggest
      that BCA treatment can effectively prevent the OVX-induced increase in bone loss
      and bone turnover possibly by increasing osteoblastic activities and decreasing
      osteoclastic activities.

PMID- 23533503
TI  - Tanshinone IIA and Cryptotanshinone Prevent Mitochondrial Dysfunction in Hypoxia
      Induced H9c2 Cells: Association to Mitochondrial ROS, Intracellular Nitric Oxide,
      and Calcium Levels.
AB  - The protective actions of tanshinones on hypoxia-induced cell damages have been
      reported, although the mechanisms have not been fully elucidated. Given the
      importance of nitric oxide (NO) and reactive oxygen species (ROS) in regulation
      of cell functions, the present study investigated the effects of two major
      tanshinones, Tanshinone IIA (TIIA) and cryptotanshinone (CT), on hypoxia-induced
      myocardial cell injury and its relationships with intracellular NO and ROS,
      calcium, and ATP levels in H9c2 cells. Chronic hypoxia significantly reduced cell
      viability which accompanied with LDH release, increase in mitochondrial ROS,
      intracellular NO and calcium levels, decrease in superoxide dismutase (SOD)
      activity, and cellular ATP contents. TIIA and CT significantly prevented cell
      injury by increasing cell viability and decreasing LDH release. The protective
      effects of tanshinones were associated with reduced mitochondrial superoxide
      production and enhanced mitochondrial SOD activity. Tanshinones significantly
      reduced intracellular NO and Ca(2+) levels. ATP levels were also restored by
      TIIA. These findings suggest that the cytoprotective actions of tanshinones may
      involve regulation of intracellular NO, Ca(2+), ATP productions, mitochondrial
      superoxide production, and SOD activity, which contribute to their actions
      against hypoxia injuries.

PMID- 23533502
TI  - Novel bioactivity of ellagic Acid in inhibiting human platelet activation.
AB  - Pomegranates are widely consumed either as fresh fruit or in beverage form as
      juice and wine. Ellagic acid possesses potent antioxidative properties; it is
      known to be an effective phytotherapeutic agent with antimutagenic and
      anticarcinogenic qualities. Ellagic acid (20 to 80  MU M) exhibited a potent
      activity in inhibiting platelet aggregation stimulated by collagen; however, it
      did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or
      U46619. Treatment with ellagic acid (50 and 80  MU M) significantly inhibited
      platelet activation stimulated by collagen; this alteration was accompanied by
      the inhibition of relative [Ca(2+)] i mobilization, and the phosphorylation of
      phospholipase C (PLC) gamma 2, protein kinase C (PKC), mitogen-activated protein
      kinases (MAPKs), and Akt, as well as hydroxyl radical (OH(?)) formation. In
      addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated
      by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC
      activation and platelet aggregation stimulated by PDBu. This study is the first
      to show that, in addition to being considered a possible agent for preventing
      tumor growth, ellagic acid possesses potent antiplatelet properties. It appears
      to initially inhibit the PLCgamma2-PKC cascade and/or hydroxyl radical formation,
      followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting
      platelet aggregation.

PMID- 23533504
TI  - Massage therapy for neck and shoulder pain: a systematic review and meta
      analysis.
AB  - Objective. To evaluate the effectiveness of massage therapy (MT) for neck and
      shoulder pain. Methods. Seven English and Chinese databases were searched until
      December 2011 for randomized controlled trials (RCTs) of MT for neck and shoulder
      pain. The methodological quality of RCTs was assessed based on PEDro scale. The
      meta-analyses of MT for neck and shoulder pain were performed. Results. Twelve
      high-quality studies were included. In immediate effects, the meta-analyses
      showed significant effects of MT for neck pain (standardised mean difference,
      SMD, 1.79; 95% confidence intervals, CI, 1.01 to 2.57; P < 0.00001) and shoulder
      pain (SMD, 1.50; 95% CI, 0.55 to 2.45; P = 0.002) versus inactive therapies. And
      MT showed short-term effects for shoulder pain (SMD, 1.51; 95% CI, 0.53 to 2.49;
      P = 0.003). But MT did not show better effects for neck pain (SMD, 0.13; 95% CI, 
      0.38 to 0.63; P = 0.63) or shoulder pain (SMD, 0.88; 95% CI, -0.74 to 2.51; P =
      0.29) than active therapies. In addition, functional status of the shoulder was
      not significantly affected by MT. Conclusion. MT may provide immediate effects
      for neck and shoulder pain. However, MT does not show better effects on pain than
      other active therapies. No evidence suggests that MT is effective in functional
      status.

PMID- 23533505
TI  - Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH2-Terminal Kinase
      Dependent Apoptosis in Lung Fibroblasts.
AB  - Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by
      fibroblasts proliferation and extracellular matrix accumulation. Induction of
      fibroblast apoptosis therefore plays a crucial role in the resolution of this
      disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic
      compound, has been reported to induce apoptosis in tumor cell lines and renal
      fibroblasts. The present study was undertaken to examine the role of mitogen
      activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic
      acid. We found that treatment with gallic acid resulted in activation of c-Jun
      NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and
      protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts.
      Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown
      (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and
      Fas expression, and abolished apoptosis induced by gallic acid. Moreover,
      treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase)
      effectively diminished gallic acid-induced hydrogen peroxide production, JNK and
      p53 activation, and cell death. These observations imply that gallic acid
      mediated hydrogen peroxide formation acts as an initiator of JNK signaling
      pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts.

PMID- 23533506
TI  - Metabonomics study of essential hypertension and its chinese medicine subtypes by
      using gas chromatography-mass spectrometry and nuclear magnetic resonance
      spectroscopy.
AB  - A metabonomic study was performed to investigate the metabolic mechanism of
      essential hypertension and its Chinese medicine subtypes, including "Yin
      deficiency and Yang-hyperactivity syndrome" (YDYHS) and "Yin-Yang deficiency
      syndrome" (YYDS). Plasma samples from 22 healthy volunteers, 31 hypertensive
      patients with YDYHS, and 29 hypertensive patients with YYDS were analyzed by (1)H
      NMR spectroscopy and gas chromatography coupled with mass spectrometry (GC-MS).
      The three groups were distinctly classified by principal components analysis
      (PCA) and partial least squares discriminant analysis (PLS-DA). According to
      identified biomarkers and their related pathways, abnormal glucose metabolism
      might be the main common pathway from YDYHS to YYDS, and sympathetic nervous
      system activation would play an important role in the pathogenesis of YDYHS,
      while a low metabolic rate usually occurred in YYDS.

PMID- 23533507
TI  - A Systematic Review of the Efficacy of Centella asiatica for Improvement of the
      Signs and Symptoms of Chronic Venous Insufficiency.
AB  - We aimed to assess the efficacy of Centella asiatica for improvement of the signs
      and symptoms of chronic venous insufficiency (CVI). We searched 13 electronic
      databases including the Cochrane Central Register of Controlled Trials for
      randomised controlled trials assessing the efficacy of Centella asiatica for CVI.
      Two review authors independently selected studies, assessed the risks of bias of
      included studies and extracted data. The treatment effects of similar studies
      were pooled whenever appropriate. Eight studies met the inclusion criteria. The
      pooling of data of similar studies showed that Centella asiatica significantly
      improved microcirculatory parameters such as transcutaneous partial pressure of
      CO2 and O2, rate of ankle swelling and venoarteriolar response. Three out of the
      eight studies did not provide quantitative data. However, these studies reported
      that patients treated with Centella asiatica showed significant improvement in
      CVI signs such as leg heaviness, pain and oedema. Our results show that Centella
      asiatica may be beneficial for improving signs and symptoms of CVI but this
      conclusion needs to be interpreted with caution as most of the studies were
      characterised by inadequate reporting and thus had unclear risks of bias, which
      may threaten the validity of the conclusions.

PMID- 23533508
TI  - Inhibitory effects of traditional herbal formula pyungwi-san on inflammatory
      response in vitro and in vivo.
AB  - Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the
      effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide
      synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor
      necrosis factor- alpha (TNF- alpha )) and nuclear factor-kappa B (NF- kappa B) as
      well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-)
      induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75,
      and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2,
      iNOS, NF- kappa B, and MAPKs as well as production of prostaglandin E2 (PGE2),
      nitric oxide (NO), IL-6, and TNF- alpha induced by LPS. Our results demonstrate
      that PWS possesses anti-inflammatory activities via decreasing production of pro
      inflammatory mediators through suppression of the signaling pathways of NF- kappa
      B and MAPKs in LPS-induced macrophage cells. More importantly, results of the
      carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In
      addition, it is considered that PWS also inhibits the acute edematous
      inflammations through suppression of mast cell degranulations and inflammatory
      mediators, including COX-2, iNOS and TNF- alpha . Thus, our findings may provide
      scientific evidence to explain the anti-inflammatory properties of PWS in vitro
      and in vivo.

PMID- 23533509
TI  - A Metabolomics Profiling Study in Hand-Foot-and-Mouth Disease and Modulated
      Pathways of Clinical Intervention Using Liquid Chromatography/Quadrupole Time-of
      Flight Mass Spectrometry.
AB  - Hand-foot-and-mouth disease (HFMD), with poorly understood pathogenesis, has
      become a major public health threat across Asia Pacific. In order to characterize
      the metabolic changes of HFMD and to unravel the regulatory role of clinical
      intervention, we have performed a metabolomics approach in a clinical trial. In
      this study, metabolites profiling was performed by liquid
      chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) platform
      from the HFMD clinical patient samples. The outcome of this study suggested that
      31 endogenous metabolites were mainly involved and showed marked perturbation in
      HFMD patients. In addition, combination therapy intervention showed normalized
      tendency in HFMD patients in differential pathway. Taken together, these results
      indicate that metabolomics approach can be used as a complementary tool for the
      detection and the study of the etiology of HFMD.

PMID- 23533510
TI  - Effect of Modified Formula Radix Hedysari on the Amplification Effect during
      Peripheral Nerve Regeneration.
AB  - Many studies have demonstrated a compensatory amplification phenomenon during
      nerve regeneration. When a relatively fine nerve is used as a donor to connect to
      a distal nerve after transection, the donor nerve regenerates more collaterals
      than its own fibers, which extend to the distal stump, grow into distal
      endoneurial tubes, and finally reach and dominate the target organs. This is
      known as the amplification phenomenon. In this study, we investigated the
      amplification phenomenon in rats treated with Modified Formula Radix Hedysari
      (MFRH) as adjuvant therapy for 12 weeks. The rats were divided into three groups
      at random (six animals in each group). In the model group and the treatment
      group, the proximal common peroneal nerve was used as a donor nerve to connect to
      the distal tibial nerve. Rats in the normal group did not undergo surgery. After
      surgery, the treatment group was administered MFRH as systemic therapy, while the
      model group and the normal group were not given treatment. The results
      demonstrated that the nerve conduction velocity, the fiber diameter, the axon
      diameter, the number of regenerating nerve fibers, and the amplification ratio
      were better in the treatment group than in the model group, suggesting that MFRH
      promoted the nerve amplification effect.

PMID- 23533511
TI  - Electroacupuncture modulates reproductive hormone levels in patients with primary
      ovarian insufficiency: results from a prospective observational study.
AB  - To investigate the effects of electroacupuncture (EA) on serum FSH, E2, and LH
      levels, women with primary ovarian insufficiency (POI) were treated with EA once
      a day, five times a week for the first four weeks and once every other day, three
      times a week, for the following two months, and then were followed up for three
      months. Serum E2, FSH, and LH levels were measured at baseline, at the end of
      treatment, and during followup. A total of 11 women with POI were included in
      this prospective consecutive case series study. Compared with baseline, patients'
      serum E2 increased, FSH decreased, and LH decreased (P = 0.002, 0.001, and 0.002,
      resp.) after EA treatment, and these effects persisted during followup. With
      treatment, 10 patients resumed menstruation (10/11, 90.91%), whereas one patient
      remained amenorrhea. During followup, two patients, including the one with
      amenorrhea during treatment, reported absence of menstruation. Temporary pain
      occurred occasionally, and no other adverse events were found during treatment.
      The results suggest that EA could decrease serum FSH and LH levels and increase
      serum E2 level in women with POI with little or no side effects; however, further
      randomized control trials are needed.

PMID- 23533512
TI  - Antiaging active natural products.

PMID- 23533513
TI  - Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic
      Review.
AB  - Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract
      for patients with early diabetic nephropathy. Methods. Randomised controlled
      trials (RCTs) conducted on adults with early diabetic nephropathy which used
      Gingko biloba extract were included. The major databases were searched, and
      manufacturers of Gingko biloba products were contacted for information on any
      published or unpublished studies. Two authors independently extracted the data
      from the included studies. Data analysis was conducted using Review Manager 5.0
      software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased
      the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum
      creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved
      hemorheology. The methodological quality in the included studies was low. The
      explicit generation of the allocation sequence was described in only 6 trials.
      None of the included trials were confirmed to use blinding. Three studies had
      observed adverse events. One study using angiotensin-converting enzyme inhibitor
      (ACEi) reported mild cough in both groups. No serious adverse effects were
      reported. Conclusions. Gingko biloba extract is a valuable drug which has
      prospect in treating early diabetic nephropathy, especially with high UAER
      baseline level. The safety for early diabetic nephropathy is uncertain. Long
      term, double-blinded RCTs with large sample sizes are still needed to provide
      stronger evidence.

PMID- 23533514
TI  - Methanolic extracts of bitter melon inhibit colon cancer stem cells by affecting
      energy homeostasis and autophagy.
AB  - Bitter melon fruit is recommended in ancient Indian and Chinese medicine for
      prevention/treatment of diabetes. However its effects on cancer progression are
      not well understood. Here, we have determined the efficacy of methanolic extracts
      of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit
      (BMW) and skin (BMSk) extracts showed significant inhibition of cell
      proliferation and colony formation, with BMW showing greater efficacy. In
      addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW
      induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were
      undergoing autophagy and not apoptosis. Further confirmation of autophagy was
      obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7
      and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with
      activation of AMP activated protein kinase; on the other hand, exogenous
      additions of ATP lead to revival of cell proliferation. Finally, BMW treatment
      results in a dose-dependent reduction in the number and size of colonospheres.
      The extracts also decreased the expression of DCLK1 and Lgr5, markers of
      quiescent, and activated stem cells. Taken together, these results suggest that
      the extracts of bitter melon can be an effective preventive/therapeutic agent for
      colon cancer.

PMID- 23533515
TI  - Blinding measured: a systematic review of randomized controlled trials of
      acupuncture.
AB  - Background. There is no agreement among researchers on viable controls for
      acupuncture treatment, and the assessment of the effectiveness of blinding and
      its interpretation is rare. Purpose. To systematically assess the effectiveness
      of blinding (EOB) in reported acupuncture trials; to explore results of RCTs
      using a quantitative measure of EOB. Data Sources. A systematic review of
      published sham RCTs that assessed blinding. Study Selection. Five hundred and
      ninety studies were reviewed, and 54 studies (4783 subjects) were included. Data
      Extraction. The number of patients who guessed their treatment identity was
      extracted from each study. Variables with possible influence on blinding were
      identified. Data Synthesis. The blinding index was calculated for each study.
      Based on blinding indexes, studies were congregated into one of the nine blinding
      scenarios. Individual study characteristics were explored for potential
      association with EOB. Limitations. There is a possibility of publication or
      reporting bias. Conclusions. The most common scenario was that the subjects
      believed they received verum acupuncture regardless of the actual treatment
      received, and overall the subject blinding in the acupuncture studies was
      satisfactory, with 61% of study participants maintaining ideal blinding.
      Objectively calculated blinding data may offer meaningful and systematic ways to
      further interpret the findings of RCTs.

PMID- 23533516
TI  - Therapeutic efficacy of fuzheng-huayu tablet based traditional chinese medicine
      syndrome differentiation on hepatitis-B-caused cirrhosis: a multicenter double
      blind randomized controlled trail.
AB  - Aim. To evaluate and predict the therapeutic efficacy of Fuzheng-Huayu tablet
      (FZHY) based traditional Chinese Medicine (TCM) syndrome differentiation or TCM
      symptoms on chronic hepatitis B caused cirrhosis (HBC). Methods. The trial was
      designed according to CONSORT statement. It was a multi-center, double-blind,
      randomized, placebo-controlled trail. Several clinical parameters, Child-Pugh
      classification and TCM symptoms were detected and evaluated. The FZHY efficacy
      was predicted by an established Bayes forecasting method following the Bayes
      classification model. Results. The levels of HA and TCM syndrome score in FZHY
      group were significantly decreased (P < 0.05) compared to placebo group,
      respectively. The efficacy of FZHY on TCM syndrome score in HBC patients with
      some TCM syndromes was better. In TCM syndrome score evaluation, there were 53
      effective and 22 invalid in FZHY group. TCM symptoms predicted FZHY efficacy on
      HBC were close to Child-Pugh score prediction. Conclusion. FZHY decreases the
      levels of HA and TCM syndrome scores, improves the life quality of HBC patients.
      Moreover, there were different therapeutic efficacies among different TCM
      syndromes, indicating that accurate TCM syndrome differentiation might guide the
      better TCM treatment. Furthermore, the FZHY efficacy was able to predict by Bayes
      forecasting method through the alteration of TCM symptoms.

PMID- 23533517
TI  - The Extract of Herbal Medicines Activates AMP-Activated Protein Kinase in Diet
      Induced Obese Rats.
AB  - Our study investigated whether the extract of six herbal medicines (OB-1) has an
      inhibitory effect on obesity. High-fat diet-(HFD-) induced rats and controls were
      treated with 40 mg/100 g body weight of OB-1 or saline once a day for 5 weeks.
      After significant changes in body weight were induced, OB-1 and saline were
      administered to each subgroup of HFD and control groups for additional 5 weeks.
      No statistically significant decrease of body weight in OB-1-treated rats was
      found compared to controls. However, OB-1-treated rats were found to be more
      active in an open-field test and have a reduction in the size of adipocytes
      compared to controls. We observed no changes in the mRNA expressions of leptin
      and adiponectin from adipocytes between OB-1- and saline-treated rats with HFD
      induced obesity group. However, OB-1 treatments were shown to be inversely
      correlated with accumulation of lipid droplets in liver tissue, suggesting that
      OB-1 could inhibit a lipid accumulation by blocking the pathway related to lipid
      metabolism. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK)
      was significantly increased in OB-1-treated rats with HFD compared to controls.
      These results suggest that OB-1 has no direct antiobesity effect and, however,
      could be a regulator of cellular metabolism.

PMID- 23533518
TI  - In Vitro and In Vivo Evaluation of Polyherbal Formulation against Russell's Viper
      and Cobra Venom and Screening of Bioactive Components by Docking Studies.
AB  - The present study emphasizes to reveal the antivenom activity of Aristolochia
      bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which
      were evaluated against venoms of Daboia russelli russelli (Russell's viper) and
      Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above
      mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200
      mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and
      0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro
      antioxidant activities sample extracts showed free radical scavenging effects in
      dose dependent manner. Computational drug design and docking studies were carried
      out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from
      Indian common krait venom. This confirmed that aristolochic acid and leucasin can
      neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a
      source of natural antioxidants and common antidote for snake bite. However,
      further studies are needed to identify the lead molecule responsible for antidote
      activity.

PMID- 23533519
TI  - Metabolic syndrome and inflammation: a critical review of in vitro and clinical
      approaches for benefit assessment of plant food supplements.
AB  - Metabolic syndrome is defined as the clustering in an individual of several
      metabolic abnormalities associated with insulin resistance, type 2 diabetes, and
      obesity, in which low-grade chronic inflammatory activity is commonly observed.
      Part of the European Project PlantLIBRA is concerned with methods to assess the
      benefits of plant food supplements (PFSs) in countering inflammatory activity and
      metabolic syndrome. This paper summarizes the current methods used for benefit
      assessment of PFS, taking into consideration only in vitro, in silico, and
      clinical methodologies used to investigate the anti-inflammatory properties of
      plants. No in silico studies (using computer simulation) related to metabolic
      syndrome were found; these methods appear to be used exclusively for identifying
      or testing potentially effective compounds in drug development. Most in vitro
      methods for the assessment of beneficial effects of botanicals or plant food
      supplements in diabetes were based on a quantitative polymerase chain reaction
      (PCR), whereas the preferred kind of clinical study was the double-blind
      randomized controlled clinical trial. Only two parameters were observed to change
      after treatment with botanicals in both in vitro and in vivo studies: interleukin
      6 and tumour necrosis factor- alpha , and these biomarkers should be carefully
      considered in future studies for PFS benefit assessment.

PMID- 23533520
TI  - Unexpected Nephrotoxicity in Male Ablactated Rats Induced by Cordyceps militaris:
      The Involvement of Oxidative Changes.
AB  - Recently, many nutraceutical products containing the powdered or extracted parts
      of C. militaris have become available for health care. Due to the increased
      morbidity and mortality, poisonings associated with the use of herbs have raised
      the universal attention. Herein, we carried out the 28-day repeated toxicity test
      in male and female ablactated rats (three weeks old) given C. militaris powder
      orally at 0 (control), 1, 2, and 3 g/kg per day. Noticeable increments of serum
      aspartate and alanine aminotransferase (ALT and AST) levels were observed for
      both sexes, suggestive of weak hepatic toxicity. Nephrotoxicity characterized by
      tubular epithelium degeneration and necrosis was observed at the high dose, and
      the male rats were more susceptible to renal toxicity than female rats. In
      addition, the genes and protein expressions of novel markers of kidney toxicity,
      such as kidney injury molecule-1 (KIM-1) were enlarged in the renal cortex and
      the urine. Moreover, C. militaris treatment significantly decreased superoxide
      dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities.
      However, the ratio of glutathione oxidized form (GSSG)/glutathione reduced form
      (GSH) was increased by C. militaris treatment. We conclude that dietary
      contamination with C. militaris may have renal toxicity potentials, at least in
      part by causing oxidative damage to the kidney.

PMID- 23533521
TI  - Fructus mume formula in the treatment of type 2 diabetes mellitus: a randomized
      controlled pilot trial.
AB  - Background. "Fructus Mume or Dark Plum" (pilule form) has been used for many
      years in Traditional Chinese Medicine (TCM) and may be a valid treatment for type
      2 diabetes mellitus (T2DM). Aim. One aspect toward efficacy validation is the
      evaluation of the blood glucose-lowering effect of Fructus Mume (FM) with T2DM
      patients in a randomized controlled trial (RCT). Methods. This pilot study uses a
      RCT procedure to assess efficacy of FM and Metformin. The trial was for 12 weeks,
      with 80 T2DM subjects. Both groups were standardized in their diet and exercise
      routine. Comparisons of several variables were analyzed. Results. No significant
      differences were found between groups in the fasting and postprandial glucose
      levels although both had significant decreases. The values of glycosylated
      hemoglobin were significantly reduced in both groups. For patients whose body
      mass index (BMI) was <23, neither FM nor Metformin had an effect on BMI; for
      those with a BMI between 23 and 25 or the BMI was >25, both FM and Metformin
      significantly reduce the BMI. Conclusions. In this pilot study, it was
      demonstrated that Fructus Mume formula may reduce the levels of blood glucose in
      patients with type 2 diabetes.

PMID- 23533522
TI  - Ethnopharmacological approaches to wound repair.

PMID- 23533523
TI  - Tetrandrine Inhibits the Wnt/ beta -Catenin Signalling Pathway and Alleviates
      Osteoarthritis: An In Vitro and In Vivo Study.
AB  - There is currently no effective drug treatment for the early phase of
      osteoarthritis (OA), one of the most common senile diseases. The goal of this
      study was to investigate the protective effect of the tetrandrine (Tet) on OA, in
      vitro and in vivo. In an in vitro experiment, quantitative real-time polymerase
      chain reaction (qRT-PCR) was used to investigate changes in gene expression upon
      the addition of Tet in chondrocytes processed with IL-1 beta ; changes in protein
      profiles were assessed by Western blotting. In vivo, to determine whether Tet has
      the protective effects on articular cartilage, a rabbit anterior cruciate
      ligament transaction model of OA was established. Expression of matrix
      metalloproteinase and beta -catenin genes increased significantly, while that of
      tissue inhibitor of metalloproteinase-1 decreased significantly in the OA group
      both in vivo and in chondrocytes. However, the changes of expression were
      reversed by Tet, and there was less cartilage degradation in vivo compared with
      the OA group, as assessed by histological and macroscopic observations. Thus, Tet
      may play a useful role in the treatment of OA through the Wnt/ beta -catenin
      signalling pathway and has potential for the treatment of OA.

PMID- 23533524
TI  - Metabolomic strategy for studying the intervention and the synergistic effects of
      the shexiang baoxin pill for treating myocardial infarction in rats.
AB  - A metabolomic approach has been developed for evaluating the therapeutic effects
      of the bioactive components and the synergistic efficacy of the Shexiang Baoxin
      Pill (SBP) on myocardial infarction (MI) in rats. The MI rats were administered
      the SBP, muscone, cinnamic acid, bufalin, ginsenoside Re, ginsenoside Rb1, cholic
      acid, borneol, and a combined version of these bioactive components (SFSBP).
      Liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS)
      was used to obtain the mass data from the rats' serum. The number of biomarkers
      that were reversed by SFSBP was greater than any of the monotherapy groups. The
      PLS-DA score plots demonstrated that the SFSBP group results were located closer
      to the sham group than any of the monotherapy groups and that the SBP group was
      located closer to the sham group than the SFSBP treatment group. The reversing
      results observed with SFSBP showed synergistic effects when compared with those
      of the individual bioactive components that were used as monotherapy. Meanwhile,
      the SBP displayed superior regulation efficacy to SFSBP in MI rats, indicating
      that there must be other active components in the SBP that were responsible for
      the treatment of MI that were not included in the SFSBP treatment.

PMID- 23533525
TI  - Evaluation on Anti-Inflammatory, Analgesic, Antitumor, and Antioxidant Potential
      of Total Saponins from Nigella glandulifera Seeds.
AB  - Nigella glandulifera seeds are used as a spice or remedy for the treatment of
      various inflammatory diseases. This study aimed to investigate analgesic
      (writhing test), anti-inflammatory (ear-induced edema, vascular permeability
      test), antioxidant, and antitumor activities of total saponins from this plant
      (TSN). TSN (6, 12, and 24 mg/kg) were exhibited analgesic and anti-inflammatory
      activities in a dose-dependent manner (P < 0.05). In D-galactose-induced ageing
      model, TSN significantly increased the plasma superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) activities (P < 0.05) and decreased the
      malondialdehyde (MDA) level compared to control group (P < 0.05). DPPH radical
      scavenging effect of TSN was also found. Moreover, TSN (20 mg/mL) showed 86.75%
      and 88.26% inhibition of the growth on Bel-7402 and Hela cells, respectively.
      Five compounds were further isolated and identified from TSN as Nigella A, B, C,
      D, and nigeglanoside, of which the content of Nigella A was 60.36 +/- 1.25 g/100
      g TSN by HPLC-ELSD method. Altogether, these results suggest that TSN could be
      considered as a potential analgesic, anti-inflammatory, antitumor, and
      antioxidant agent.

PMID- 23533526
TI  - Subamolide a induces mitotic catastrophe accompanied by apoptosis in human lung
      cancer cells.
AB  - This study investigated the anticancer effects of subamolide A (Sub-A), isolated
      from Cinnamomum subavenium, on human nonsmall cell lung cancer cell lines A549
      and NCI-H460. Treatment of cancer cells with Sub-A resulted in decreased cell
      viability of both lung cancer cell lines. Sub-A induced lung cancer cell death by
      triggering mitotic catastrophe with apoptosis. It triggered oxidant stress,
      indicated by increased cellular reactive oxygen species (ROS) production and
      decreased glutathione level. The elevated ROS triggered the activation of ataxia
      telangiectasia mutation (ATM), which further enhanced the ATF3 upregulation and
      subsequently enhanced p53 function by phosphorylation at Serine 15 and Serine
      392. The antioxidant, EUK8, significantly decreased mitotic catastrophe by
      inhibiting ATM activation, ATF3 expression, and p53 phosphorylation. The
      reduction of ATM and ATF3 expression by shRNA decreased Sub-A-mediated p53
      phosphorylation and mitotic catastrophe. Sub-A also caused a dramatic 70%
      reduction in tumor size in an animal model. Taken together, cell death of lung
      cancer cells in response to Sub-A is dependent on ROS generation, which triggers
      mitotic catastrophe followed by apoptosis. Therefore, Sub-A may be a novel
      anticancer agent for the treatment of nonsmall cell lung cancer.

PMID- 23533527
TI  - In vitro antimicrobial activity of extracts from plants used traditionally in
      South Africa to treat tuberculosis and related symptoms.
AB  - Respiratory ailments are major human killers, especially in developing countries.
      Tuberculosis (TB) is an infectious disease causing a threat to human healthcare.
      Many South African plants are used in the traditional treatment of TB and related
      symptoms, but there has not been a sufficient focus on evaluating their
      antimicrobial properties. The aim of this study was to evaluate the antimicrobial
      properties of plants used traditionally to treat TB and related symptoms against
      microorganisms (Klebsiella pneumoniae, Staphylococcus aureus, and Mycobacterium
      aurum A+) associated with respiratory infections using the microdilution assay.
      Ten plants were selected based on a survey of available literature of medicinal
      plants used in South Africa for the treatment of TB and related symptoms. The
      petroleum ether, dichloromethane, 80% ethanol, and water extracts of the selected
      plants were evaluated for antibacterial activity. Out of 68 extracts tested from
      different parts of the 10 plant species, 17 showed good antimicrobial activities
      against at least one or more of the microbial strains tested, with minimum
      inhibitory concentration ranging from 0.195 to 12.5 mg/mL. The good antimicrobial
      properties of Abrus precatorius, Terminalia phanerophlebia, Indigofera arrecta,
      and Pentanisia prunelloides authenticate their traditional use in the treatment
      of respiratory diseases. Thus, further pharmacological and phytochemical analysis
      is required.

PMID- 23533528
TI  - Induction of apoptosis and cell cycle blockade by helichrysetin in a549 human
      lung adenocarcinoma cells.
AB  - Researchers are looking into the potential development of natural compounds for
      anticancer therapy. Previous studies have postulated the cytotoxic effect of
      helichrysetin towards different cancer cell lines. In this study, we investigated
      the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four
      selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further
      elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma,
      A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed
      by A549. Changes in the nuclear morphology of A549 cells such as chromatin
      condensation and nuclear fragmentation were observed in cells treated with
      helichrysetin. Further evidence of apoptosis includes the externalization of
      phosphatidylserine and the collapse of mitochondrial membrane potential which are
      both early signs of apoptosis. These signs of apoptosis are related to cell cycle
      blockade at the S checkpoint which suggests that the alteration of the cell cycle
      contributes to the induction of apoptosis in A549. These results suggest that
      helichrysetin has great potentials for development as an anticancer agent.

PMID- 23533529
TI  - The involvement of a polyphenol-rich extract of black chokeberry in oxidative
      stress on experimental arterial hypertension.
AB  - The aim of this study is to characterize the content of Aronia melanocarpa
      Elliott (black chokeberry) extract and also to estimate the influence of
      polyphenolic compounds contained in chokeberries on oxidative stress, on an L
      NAME-induced experimental model of arterial hypertension. The rat blood pressure
      values were recorded using a CODA Noninvasive Blood Pressure System. HPLC/DAD
      coupled with ElectroSpray Ionization-Mass Spectrometry allowed identification of
      five phenolic compounds in berries ethanolic extract as follows: chlorogenic
      acid, kuromanin, rutin, hyperoside, and quercetin. The serous activity of
      glutathione-peroxidase (GSH-Px) has significantly lower values in the
      hypertensive (AHT) group as compared to the group protected by polyphenols (AHT +
      P). The total antioxidant capacity (TAC) values are lower in the AHT group and
      they are significantly higher in the AHT + P group. All the measured blood
      pressure components revealed a biostatistically significant blood pressure drop
      between the AHT group and the AHT + P group. The results reveal the normalization
      of the reduced glutathion (GSH) concentration as well as a considerable reduction
      in the malondialdehyde (MDA) serum concentration in the AHT + P group. Ethanolic
      extract of black chokeberry fruits not only has a potential value as a
      prophylactic agent but also may function as a nutritional supplement in the
      management of arterial hypertension.

PMID- 23533530
TI  - Simultaneous Determination of Crypto-Chlorogenic Acid, Isoquercetin, and
      Astragalin Contents in Moringa oleifera Leaf Extracts by TLC-Densitometric
      Method.
AB  - Moringa oleifera Lamarck (Moringaceae) is used as a multipurpose medicinal plant
      for the treatment of various diseases. Isoquercetin, astragalin, and crypto
      chlorogenic acid have been previously found to be major active components in the
      leaves of this plant. In this study, a thin-layer-chromatography (TLC
      )densitometric method was developed and validated for simultaneous quantification
      of these major components in the 70% ethanolic extracts of M. oleifera leaves
      collected from 12 locations. The average amounts of crypto-chlorogenic acid,
      isoquercetin, and astragalin were found to be 0.0473, 0.0427, and 0.0534% dry
      weight, respectively. The method was validated for linearity, precision,
      accuracy, limit of detection, limit of quantitation, and robustness. The
      linearity was obtained in the range of 100-500 ng/spot with a correlation
      coefficient (r) over 0.9961. Intraday and interday precisions demonstrated
      relative standard deviations of less than 5%. The accuracy of the method was
      confirmed by determining the recovery. The average recoveries of each component
      from the extracts were in the range of 98.28 to 99.65%. Additionally, the leaves
      from Chiang Mai province contained the highest amounts of all active components.
      The proposed TLC-densitometric method was simple, accurate, precise, and cost
      effective for routine quality controlling of M. oleifera leaf extracts.

PMID- 23533531
TI  - Zuo Jin Wan, a Traditional Chinese Herbal Formula, Reverses P-gp-Mediated MDR In
      Vitro and In Vivo.
AB  - Zuo Jin Wan (ZJW), a typical traditional Chinese medicine (TCM) formula, has been
      identified to have anticancer activity in recent studies. In this study, we
      determined the underlying mechanism of ZJW in the reversal effect of multidrug
      resistance on colorectal cancer in vitro and in vivo. Our results showed that ZJW
      significantly enhanced the sensitivity of chemotherapeutic drugs in HCT116/L-OHP,
      SGC7901/DDP, and Bel/Fu MDR cells. Moreover, combination of chemotherapy with ZJW
      could reverse the drug resistance of HCT116/L-OHP cells, increase the sensitivity
      of HCT116/L-OHP cells to L-OHP, DDP, 5-Fu, and MMC in vitro, and inhibit the
      tumor growth in the colorectal MDR cancer xenograft model. ICP-MS results showed
      that ZJW could increase the concentration of chemotherapeutic drugs in HCT116/L
      OHP cells in a dose-dependent manner. Furthermore, we showed that ZJW could
      reverse drug resistance of colorectal cancer cells by decreasing P-gp level in
      vitro and in vivo, which has been represented as one of the major mechanisms that
      contribute to the MDR phenotype. Our study has provided the first direct evidence
      that ZJW plays an important role in reversing multidrug resistance of human
      colorectal cancer and may be considered as a useful target for cancer therapy.

PMID- 23533532
TI  - Cognitive-neural effects of brush writing of chinese characters: cortical
      excitation of theta rhythm.
AB  - Chinese calligraphy has been scientifically investigated within the contexts and
      principles of psychology, cognitive science, and the cognitive neuroscience. On
      the basis of vast amount of research in the last 30 years, we have developed a
      cybernetic theory of handwriting and calligraphy to account for the intricate
      interactions of several psychological dimensions involved in the dynamic act of
      graphic production. Central to this system of writing are the role of sensory,
      bio-, cognitive, and neurofeedback mechanisms for the initiation, guidance, and
      regulation of the writing motions vis-a-vis visual-geometric variations of
      Chinese characters. This experiment provided the first evidence of cortical
      excitation in EEG theta wave as a neural hub that integrates information coming
      from changes in the practitioner's body, emotions, and cognition. In addition, it
      has also confirmed neurofeedback as an essential component of the cybernetic
      theory of handwriting and calligraphy.

PMID- 23533533
TI  - Correlation between Platelet Gelsolin and Platelet Activation Level in Acute
      Myocardial Infarction Rats and Intervention Effect of Effective Components of
      Chuanxiong Rhizome and Red Peony Root.
AB  - The biological role of platelet gelsolin in platelet activation of acute
      myocardial infarction is not defined. In order to provide a potential new
      antiplatelet target for Chinese medicine and to elucidate the contribution of
      Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony
      root, in this study, we randomly allocated Sprague Dawley rats to left anterior
      descending coronary artery ligation or sham surgery and different drug
      prophylaxis as control. We found that gelsolin is highly expressed in platelet
      rich plasma and lowly expressed in platelet poor plasma, accompanied by the high
      platelet activation level in model rats; plasma actin filaments and mean
      fluorescence intensity (MFI) of platelet calcium ion increased and plasma vitamin
      D binding protein decreased in model rats. Xiongshao capsule could inhibit the
      gelsolin expression in platelet rich plasma and ischemic heart tissue
      simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium
      ion. Our study concludes that platelet gelsolin is an important contributor to
      platelet activation, and platelet gelsolin inhibition may form a novel target for
      antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug
      for antiplatelet and aspirin-like cardioprotection effect.

PMID- 23533534
TI  - Ontology-oriented diagnostic system for traditional Chinese medicine based on
      relation refinement.
AB  - Although Chinese medicine treatments have become popular recently, the
      complicated Chinese medical knowledge has made it difficult to be applied in
      computer-aided diagnostics. The ability to model and use the knowledge becomes an
      important issue. In this paper, we define the diagnosis in Traditional Chinese
      Medicine (TCM) as discovering the fuzzy relations between symptoms and syndromes.
      An Ontology-oriented Diagnosis System (ODS) is created to address the knowledge
      based diagnosis based on a well-defined ontology of syndromes. The ontology
      transforms the implicit relationships among syndromes into a machine
      interpretable model. The clinical data used for feature selection is collected
      from a national TCM research institute in China, which serves as a training
      source for syndrome differentiation. The ODS analyzes the clinical cases to
      obtain a statistical mapping relation between each syndrome and associated
      symptom set, before rechecking the completeness of related symptoms via ontology
      refinement. Our diagnostic system provides an online web interface to interact
      with users, so that users can perform self-diagnosis. We tested 12 common
      clinical cases on the diagnosis system, and it turned out that, given the agree
      metric, the system achieved better diagnostic accuracy compared to nonontology
      method-92% of the results fit perfectly with the experts' expectations.

PMID- 23533535
TI  - Ultrasound common carotid artery segmentation based on active shape model.
AB  - Carotid atherosclerosis is a major reason of stroke, a leading cause of death and
      disability. In this paper, a segmentation method based on Active Shape Model
      (ASM) is developed and evaluated to outline common carotid artery (CCA) for
      carotid atherosclerosis computer-aided evaluation and diagnosis. The proposed
      method is used to segment both media-adventitia-boundary (MAB) and lumen-intima
      boundary (LIB) on transverse views slices from three-dimensional ultrasound (3D
      US) images. The data set consists of sixty-eight, 17 * 2 * 2, 3D US volume data
      acquired from the left and right carotid arteries of seventeen patients (eight
      treated with 80 mg atorvastatin and nine with placebo), who had carotid stenosis
      of 60% or more, at baseline and after three months of treatment. Manually
      outlined boundaries by expert are adopted as the ground truth for evaluation. For
      the MAB and LIB segmentations, respectively, the algorithm yielded Dice
      Similarity Coefficient (DSC) of 94.4% +/- 3.2% and 92.8% +/- 3.3%, mean absolute
      distances (MAD) of 0.26 +/- 0.18 mm and 0.33 +/- 0.21 mm, and maximum absolute
      distances (MAXD) of 0.75 +/- 0.46 mm and 0.84 +/- 0.39 mm. It took 4.3 +/- 0.5
      mins to segment single 3D US images, while it took 11.7 +/- 1.2 mins for manual
      segmentation. The method would promote the translation of carotid 3D US to
      clinical care for the monitoring of the atherosclerotic disease progression and
      regression.

PMID- 23533536
TI  - The effect of edge definition of complex networks on protein structure
      identification.
AB  - The main objective of this study is to explore the contribution of complex
      network together with its different definitions of vertexes and edges to describe
      the structure of proteins. Protein folds into a specific conformation for its
      function depending on interactions between residues. Consequently, in many
      studies, a protein structure was treated as a complex system comprised of
      individual components residues, and edges were interactions between residues.
      What is the proper time for representing a protein structure as a network? To
      confirm the effect of different definitions of vertexes and edges in constructing
      the amino acid interaction networks, protein domains and the structural unit of
      proteins were described using this method. The identification performance of 2847
      proteins with domain/domains proved that the structure of proteins was described
      well when R(C)(alpha) was around 5.0-7.5 A, and the optimal cutoff value for
      constructing the protein structure networks was 5.0 A (C(alpha) -C(alpha)
      distances) while the ideal community division method was community structure
      detection based on edge betweenness in this study.

PMID- 23533537
TI  - Towards patient-specific modeling of coronary hemodynamics in healthy and
      diseased state.
AB  - A model describing the primary relations between the cardiac muscle and coronary
      circulation might be useful for interpreting coronary hemodynamics in case
      multiple types of coronary circulatory disease are present. The main contribution
      of the present study is the coupling of a microstructure-based heart contraction
      model with a 1D wave propagation model. The 1D representation of the vessels
      enables patient-specific modeling of the arteries and/or can serve as boundary
      conditions for detailed 3D models, while the heart model enables the simulation
      of cardiac disease, with physiology-based parameter changes. Here, the different
      components of the model are explained and the ability of the model to describe
      coronary hemodynamics in health and disease is evaluated. Two disease types are
      modeled: coronary epicardial stenoses and left ventricular hypertrophy with an
      aortic valve stenosis. In all simulations (healthy and diseased), the dynamics of
      pressure and flow qualitatively agreed with observations described in literature.
      We conclude that the model adequately can predict coronary hemodynamics in both
      normal and diseased state based on patient-specific clinical data.

PMID- 23533538
TI  - EIT-based fabric pressure sensing.
AB  - This paper presents EIT-based fabric sensors that aim to provide a pressure
      mapping using the current carrying and voltage sensing electrodes attached to the
      boundary of the fabric patch. Pressure-induced shape change over the sensor area
      makes a change in the conductivity distribution which can be conveyed to the
      change of boundary current-voltage data. This boundary data is obtained through
      electrode measurements in EIT system. The corresponding inverse problem is to
      reconstruct the pressure and deformation map from the relationship between the
      applied current and the measured voltage on the fabric boundary. Taking advantage
      of EIT in providing dynamical images of conductivity changes due to pressure
      induced shape change, the pressure map can be estimated. In this paper, the EIT
      based fabric sensor was presented for circular and rectangular sensor geometry. A
      stretch sensitive fabric was used in circular sensor with 16 electrodes and a
      pressure sensitive fabric was used in a rectangular sensor with 32 electrodes. A
      preliminary human test was carried out with the rectangular sensor for foot
      pressure mapping showing promising results.

PMID- 23533539
TI  - Group factor analysis for Alzheimer's disease.
AB  - For any neuroimaging study in an institute, brain images are normally acquired
      from healthy controls and patients using a single track of protocol.
      Traditionally, the factor analysis procedure analyzes image data for healthy
      controls and patients either together or separately. The former unifies the
      factor pattern across subjects and the latter deals with measurement errors
      individually. This paper proposes a group factor analysis model for neuroimaging
      applications by assigning separate factor patterns to control and patient groups.
      The clinical diagnosis information is used for categorizing subjects into groups
      in the analysis procedure. The proposed method allows different groups of
      subjects to share a common covariance matrix of measurement errors. The empirical
      results show that the proposed method provides more reasonable factor scores and
      patterns and is more suitable for medical research based on image data as
      compared with the conventional factor analysis model.

PMID- 23533540
TI  - Concentration-invariant odor representation in the olfactory system by
      presynaptic inhibition.
AB  - The present study investigates a network model for implementing concentration
      invariant representation for odors in the olfactory system. The network consists
      of olfactory receptor neurons, projection neurons, and inhibitory local neurons.
      Receptor neurons send excitatory inputs to projection neurons, which are
      modulated by the inhibitory inputs from local neurons. The modulation occurs at
      the presynaptic site from a receptor neuron to a projection one, leading to the
      operation of divisive normalization. The responses of local interneurons are
      determined by the total activities of olfactory receptor neurons. We find that
      with a proper parameter condition, the responses of projection neurons become
      effectively independent of the odor concentration. Simulation results confirm our
      theoretical analysis.

PMID- 23533541
TI  - Computational fluid dynamics simulations of contrast agent bolus dispersion in a
      coronary bifurcation: impact on MRI-based quantification of myocardial perfusion.
AB  - Contrast-enhanced first-pass magnetic resonance imaging (MRI) in combination with
      a tracer kinetic model, for example, MMID4, can be used to determine myocardial
      blood flow (MBF) and myocardial perfusion reserve (MPR). Typically, the arterial
      input function (AIF) required for this methodology is estimated from the left
      ventricle (LV). Dispersion of the contrast agent bolus might occur between the LV
      and the myocardial tissue. Negligence of bolus dispersion could cause an error in
      MBF determination. The aim of this study was to investigate the influence of
      bolus dispersion in a simplified coronary bifurcation geometry including one
      healthy and one stenotic branch on the quantification of MBF and MPR.
      Computational fluid dynamics (CFD) simulations were combined with MMID4.
      Different inlet boundary conditions describing pulsatile and constant flows for
      rest and hyperemia and differing outflow conditions have been investigated. In
      the bifurcation region, the increase of the dispersion was smaller than inside
      the straight vessels. A systematic underestimation of MBF values up to -16.1% for
      pulsatile flow and an overestimation of MPR up to 7.5% were found. It was shown
      that, under the conditions considered in this study, bolus dispersion can
      significantly influence the results of quantitative myocardial MR-perfusion
      measurements.

PMID- 23533542
TI  - Hybrid multilevel sparse reconstruction for a whole domain bioluminescence
      tomography using adaptive finite element.
AB  - Quantitative reconstruction of bioluminescent sources from boundary measurements
      is a challenging ill-posed inverse problem owing to the high degree of absorption
      and scattering of light through tissue. We present a hybrid multilevel
      reconstruction scheme by combining the ability of sparse regularization with the
      advantage of adaptive finite element method. In view of the characteristics of
      different discretization levels, two different inversion algorithms are employed
      on the initial coarse mesh and the succeeding ones to strike a balance between
      stability and efficiency. Numerical experiment results with a digital mouse model
      demonstrate that the proposed scheme can accurately localize and quantify source
      distribution while maintaining reconstruction stability and computational
      economy. The effectiveness of this hybrid reconstruction scheme is further
      confirmed with in vivo experiments.

PMID- 23533543
TI  - A semiautomatic segmentation algorithm for extracting the complete structure of
      acini from synchrotron micro-CT images.
AB  - Pulmonary acinus is the largest airway unit provided with alveoli where blood/gas
      exchange takes place. Understanding the complete structure of acinus is necessary
      to measure the pathway of gas exchange and to simulate various mechanical
      phenomena in the lungs. The usual manual segmentation of a complete acinus
      structure from their experimentally obtained images is difficult and extremely
      time-consuming, which hampers the statistical analysis. In this study, we develop
      a semiautomatic segmentation algorithm for extracting the complete structure of
      acinus from synchrotron micro-CT images of the closed chest of mouse lungs. The
      algorithm uses a combination of conventional binary image processing techniques
      based on the multiscale and hierarchical nature of lung structures. Specifically,
      larger structures are removed, while smaller structures are isolated from the
      image by repeatedly applying erosion and dilation operators in order, adjusting
      the parameter referencing to previously obtained morphometric data. A cluster of
      isolated acini belonging to the same terminal bronchiole is obtained without
      floating voxels. The extracted acinar models above 98% agree well with those
      extracted manually. The run time is drastically shortened compared with manual
      methods. These findings suggest that our method may be useful for taking samples
      used in the statistical analysis of acinus.

PMID- 23533544
TI  - An entropy-based automated cell nuclei segmentation and quantification:
      application in analysis of wound healing process.
AB  - The segmentation and quantification of cell nuclei are two very significant tasks
      in the analysis of histological images. Accurate results of cell nuclei
      segmentation are often adapted to a variety of applications such as the detection
      of cancerous cell nuclei and the observation of overlapping cellular events
      occurring during wound healing process in the human body. In this paper, an
      automated entropy-based thresholding system for segmentation and quantification
      of cell nuclei from histologically stained images has been presented. The
      proposed translational computation system aims to integrate clinical insight and
      computational analysis by identifying and segmenting objects of interest within
      histological images. Objects of interest and background regions are automatically
      distinguished by dynamically determining 3 optimal threshold values for the 3
      color components of an input image. The threshold values are determined by means
      of entropy computations that are based on probability distributions of the color
      intensities of pixels and the spatial similarity of pixel intensities within
      neighborhoods. The effectiveness of the proposed system was tested over 21
      histologically stained images containing approximately 1800 cell nuclei, and the
      overall performance of the algorithm was found to be promising, with high
      accuracy and precision values.

PMID- 23533545
TI  - Computational approach to seasonal changes of living leaves.
AB  - This paper proposes a computational approach to seasonal changes of living leaves
      by combining the geometric deformations and textural color changes. The geometric
      model of a leaf is generated by triangulating the scanned image of a leaf using
      an optimized mesh. The triangular mesh of the leaf is deformed by the improved
      mass-spring model, while the deformation is controlled by setting different mass
      values for the vertices on the leaf model. In order to adaptively control the
      deformation of different regions in the leaf, the mass values of vertices are set
      to be in proportion to the pixels' intensities of the corresponding user
      specified grayscale mask map. The geometric deformations as well as the textural
      color changes of a leaf are used to simulate the seasonal changing process of
      leaves based on Markov chain model with different environmental parameters
      including temperature, humidness, and time. Experimental results show that the
      method successfully simulates the seasonal changes of leaves.

PMID- 23533547
TI  - Extracorporeal pulmonary support in severe pulmonary failure in adults: a
      treatment rediscovered.
AB  - BACKGROUND: Severe, acute respiratory failure in adults still carries a high
      mortality. In recent years, improved pulmonary support techniques have been used
      increasingly alongside conventional treatment. About 1000 such treatments are
      performed in Germany annually, and the number is rising rapidly. The two types of
      systems currently in use involve venovenous extracorporeal membrane oxygenation
      (ECMO) and extracorporeal carbon dioxide elimination. METHODS: The underlying
      principles, technical implementation, efficacy, and adverse effects of the new
      techniques are summarized in the light of a selective review of the literature,
      supplemented by the authors' personal experience. Recommendations are given for
      clinical use. RESULTS: Currently, only limited high-quality data (from
      prospective randomized trials) are available to support the use of either of
      these techniques in adults. Veno-venous ECMO systems can effectively secure gas
      exchange in patients with severe respiratory failure, with experienced centers
      reporting survival rates from 63% to 75%. Either pump-free arteriovenous systems
      or low-flow ECMO systems can be used for extracorporeal carbon dioxide
      elimination. Complications can be serious or life-threatening and must,
      therefore, be rapidly recognized and treated: these include vascular injury
      during cannulation, venous thrombosis in a cannulated vessel, an increased
      hemorrhagic tendency, and thrombocytopenia. CONCLUSION: Modern miniaturized
      pulmonary support systems enable protective mechanical ventilation with low tidal
      volumes, reduce ventilator-associated lung injury, and can improve survival rates
      in critically ill patients with a manageable adverse effect profile.

PMID- 23533549
TI  - Scientific data are lacking.

PMID- 23533548
TI  - Irreversible liver failure: treatment by transplantation: part 3 of a series on
      liver cirrhosis.
AB  - BACKGROUND: Liver transplantation is the only established, causally directed
      treatment for irreversible chronic or acute liver failure. METHODS: This review
      is based on papers retrieved by a selective search in the PubMed database, the
      index of randomized controlled trials of the European Society of Organ
      Transplantation, and the Cochrane database, along with an analysis of data from
      the authors' own center. RESULTS: 1199 liver transplantations were performed in
      Germany in 2011. The most common indications were alcoholic cirrhosis (28%),
      cirrhosis of other causes (24%), and intrahepatic tumors (20%). Among recipients,
      the sex ratio was nearly 1:1 and the median age was just under 50. Across Europe,
      the 1-, 5-, and 10-year survival rates after liver transplantation were 82%, 71%
      and 61%. In our own center, the Charite in Berlin, the corresponding rates were
      90.4%, 79.6% and 70.3%, based on an experience of 100 to 120 cases per year. The
      current rate of functioning transplants five years after liver transplantation is
      52.6% in Germany and 66.2% internationally. Standard immunosuppression consists
      of a calcineurin inhibitor, tacrolimus or cyclosporine A, and steroids. Early
      complications include primary functional failure of the transplant, hemorrhage,
      thrombosis, acute rejection, and biliary complications. Over the long term,
      complications that can impair the outcome include chronic rejection, biliary
      strictures, cardiovascular and metabolic adverse effects, nephrotoxicity,
      neurotoxicity, and opportunistic infections and malignancies. CONCLUSION: Liver
      transplantation is a successful and well-established form of treatment that is
      nonetheless endangered by a shortage of donor organs and other structural and
      organizational difficulties.

PMID- 23533546
TI  - Understanding the pathogenesis of Kawasaki disease by network and pathway
      analysis.
AB  - Kawasaki disease (KD) is a complex disease, leading to the damage of
      multisystems. The pathogen that triggers this sophisticated disease is still
      unknown since it was first reported in 1967. To increase our knowledge on the
      effects of genes in KD, we extracted statistically significant genes so far
      associated with this mysterious illness from candidate gene studies and genome
      wide association studies. These genes contributed to susceptibility to KD,
      coronary artery lesions, resistance to initial IVIG treatment, incomplete KD, and
      so on. Gene ontology category and pathways were analyzed for relationships among
      these statistically significant genes. These genes were represented in a variety
      of functional categories, including immune response, inflammatory response, and
      cellular calcium ion homeostasis. They were mainly enriched in the pathway of
      immune response. We further highlighted the compelling immune pathway of NF-AT
      signal and leukocyte interactions combined with another transcription factor NF-
      kappa B in the pathogenesis of KD. STRING analysis, a network analysis focusing
      on protein interactions, validated close contact between these genes and implied
      the importance of this pathway. This data will contribute to understanding
      pathogenesis of KD.

PMID- 23533550
TI  - Limited range of indications for cannabis.

PMID- 23533551
TI  - In reply.

PMID- 23533552
TI  - Surgical resection should be viewed with skepticism in patients with bladder
      cancer.

PMID- 23533553
TI  - In reply.

PMID- 23533555
TI  - Cannabis therapy.

PMID- 23533554
TI  - Assessing prognosis following cardiopulmonary resuscitation and therapeutic
      hypothermia-a critical discussion of recent studies.
AB  - BACKGROUND: The prognosis of patients who are comatose after cardiopulmonary
      resuscitation (CPR) is poor but can be improved by mild therapeutic hypothermia.
      We studied the question whether the known, reliable indicators of a poor
      prognosis after CPR are also valid for patients treated with CPR and hypothermia.
      METHODS: This review is based on a selective search of the PubMed database for
      recent articles on the assessment of prognosis in persons who are comatose after
      CPR and therapeutic hypothermia. RESULTS: On the basis of 21 clinical trials, 4
      of which yielded level I evidence, 9 level II evidence, and 8 level III evidence,
      the following were identified as reliable indicators of a poor prognosis:
      generalized myoclonus, bilateral absence of the pupillary light response or of
      the corneal reflex, bilateral absence of the cortical components of median nerve
      somatosensory evoked potentials, a burst-suppression or isoelectric EEG,
      continuous generalized epileptiform discharges, and an elevated serum
      concentration of neuron-specific enolase (with a higher cutoff value than for
      normothermic patients). CONCLUSION: If the prognosis is poor, this should be
      thoroughly discussed with the patient's family, and the nature and extent of
      further intensive treatment should be reconsidered. The patient's wishes, if
      known, are paramount. Any decision to withhold care should be taken only if there
      are multiple concurrent indicators of a poor prognosis. If only one such
      indicator is present, or if the findings are inconsistent, such decisions should
      be postponed.

PMID- 23533556
TI  - Cannabis therapy.

PMID- 23533557
TI  - Blocking fear and anxiety.

PMID- 23533558
TI  - Specific developmental disorders of scholastic skills.

PMID- 23533559
TI  - Blind and deaf?

PMID- 23533560
TI  - Visual disorders.

PMID- 23533561
TI  - Specific immunotherapy-indications and mode of action.
AB  - BACKGROUND: It is estimated that up to 24% of the population in Germany suffers
      from allergic rhinoconjunctivitis and 5% from allergic asthma. Allergic
      rhinoconjunctivitis is closely related to other atopic diseases. METHODS: This
      review is based on pertinent publications retrieved by a selective search of the
      Medline database, guidelines from Germany and abroad, and Cochrane meta-analyses.
      RESULTS: Specific immunotherapy (SIT) is the only diseases-modifying treatment
      option for allergies. Meta-analysis reveals standardized mean differences in
      allergic rhinitis symptom scores of -0.73 for subcutaneous immunotherapy (SCIT)
      and -0.49 for sublingual immunotherapy (SLIT); the corresponding mean differences
      in medication scores are -0.57 and -0.32, respectively. The treatment should be
      carried out for at least three years. It is indicated when the symptoms are
      severe and allergen avoidance is not a realistic option. The efficacy of
      treatment depends on the allergen dose; thus, every allergen preparation should
      be evaluated individually, independent of route of administration. SCIT can cause
      systemic adverse effects, including anaphylaxis. SLIT is safer but often causes
      allergic symptoms of the oral mucosa at the beginning of treatment. CONCLUSION:
      Even though the efficacy of SIT is well documented, it is still underused. SIT
      should be offered as standard treatment to patients suffering from allergic
      rhinitis.

PMID- 23533562
TI  - On the relevance of sophisticated structural annotations for disulfide
      connectivity pattern prediction.
AB  - Disulfide bridges strongly constrain the native structure of many proteins and
      predicting their formation is therefore a key sub-problem of protein structure
      and function inference. Most recently proposed approaches for this prediction
      problem adopt the following pipeline: first they enrich the primary sequence with
      structural annotations, second they apply a binary classifier to each candidate
      pair of cysteines to predict disulfide bonding probabilities and finally, they
      use a maximum weight graph matching algorithm to derive the predicted disulfide
      connectivity pattern of a protein. In this paper, we adopt this three step
      pipeline and propose an extensive study of the relevance of various structural
      annotations and feature encodings. In particular, we consider five kinds of
      structural annotations, among which three are novel in the context of disulfide
      bridge prediction. So as to be usable by machine learning algorithms, these
      annotations must be encoded into features. For this purpose, we propose four
      different feature encodings based on local windows and on different kinds of
      histograms. The combination of structural annotations with these possible
      encodings leads to a large number of possible feature functions. In order to
      identify a minimal subset of relevant feature functions among those, we propose
      an efficient and interpretable feature function selection scheme, designed so as
      to avoid any form of overfitting. We apply this scheme on top of three supervised
      learning algorithms: k-nearest neighbors, support vector machines and extremely
      randomized trees. Our results indicate that the use of only the PSSM (position
      specific scoring matrix) together with the CSP (cysteine separation profile) are
      sufficient to construct a high performance disulfide pattern predictor and that
      extremely randomized trees reach a disulfide pattern prediction accuracy of
      [Formula: see text] on the benchmark dataset SPX[Formula: see text], which
      corresponds to [Formula: see text] improvement over the state of the art. A web
      application is available at http://m24.giga.ulg.ac.be:81/x3CysBridges.

PMID- 23533563
TI  - Novel risk factors for premature peripheral arterial occlusive disease in non
      diabetic patients: a case-control study.
AB  - BACKGROUND: This study aimed to determine the prevalence of genetic and
      environmental vascular risk factors in non diabetic patients with premature
      peripheral arterial disease, either peripheral arterial occlusive disease or
      thromboangiitis obliterans, the two main entities of peripheral arterial disease,
      and to established whether some of them are specifically associated with one or
      another of the premature peripheral arterial disease subgroups. METHODS AND
      RESULTS: This study included 113 non diabetic patients with premature peripheral
      arterial disease (diagnosis <45-year old) presenting either a peripheral arterial
      occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241
      controls matched for age and gender. Both patient groups demonstrated common
      traits including cigarette smoking, low physical activity, decreased levels of
      HDL-cholesterol, apolipoprotein A-I, pyridoxal 5'-phosphate (active form of B6
      vitamin) and zinc. Premature peripheral arterial occlusive disease was
      characterized by the presence of a family history of peripheral arterial and
      carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein
      (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden
      (OR 5.1, 95% CI) and the glycoprotein Ia(807T,837T,873A) allele (OR 2.3, 95% CI).
      In thromboangiitis obliterans group, more patients were regular consumers of
      cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR
      6.5, 95% CI). CONCLUSIONS: According to our results from a non exhaustive list of
      study parameters, we might hypothesize for 1) a genetic basis for premature
      peripheral arterial occlusive disease development and 2) the prevalence of
      environmental factors in the development of thromboangiitis obliterans (tobacco
      and cannabis). Moreover, for the first time, we demonstrated that the
      807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk
      for development of peripheral atherosclerosis in premature peripheral arterial
      occlusive disease.

PMID- 23533564
TI  - Curcumin as a potent and selective inhibitor of 11beta-hydroxysteroid
      dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats.
AB  - BACKGROUND: 11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) activates
      glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome.
      11beta-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin
      and its derivatives as selective inhibitors of 11beta-HSD1 have not been
      reported. METHODOLOGY: Curcumin and its 12 derivatives were tested for their
      potencies of inhibitory effects on human and rat 11beta-HSD1 with selectivity
      against 11beta-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley
      rats with high-fat-diet-induced metabolic syndrome for 2 months. RESULTS AND
      CONCLUSIONS: Curcumin exhibited inhibitory potency against human and rat 11beta
      HSD1 in intact cells with IC50 values of 2.29 and 5.79 uM, respectively, with
      selectivity against 11beta-HSD2 (IC50, 14.56 and 11.92 uM). Curcumin was a
      competitive inhibitor of human and rat 11beta-HSD1. Curcumin reduced serum
      glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat
      diet-induced obese rats. Four curcumin derivatives had much higher potencies for
      Inhibition of 11beta-HSD1. One of them is (1E,4E)-1,5-bis(thiophen-2-yl) penta
      1,4-dien-3-one (compound 6), which had IC50 values of 93 and 184 nM for human and
      rat 11beta-HSD1, respectively. Compound 6 did not inhibit human and rat kidney
      11beta-HSD2 at 100 uM. In conclusion, curcumin is effective for the treatment of
      metabolic syndrome and four novel curcumin derivatives had high potencies for
      inhibition of human 11beta-HSD1 with selectivity against 11beta-HSD2.

PMID- 23533566
TI  - Hydrodynamic and thermal slip effect on double-diffusive free convective boundary
      layer flow of a nanofluid past a flat vertical plate in the moving free stream.
AB  - The effects of hydrodynamic and thermal slip boundary conditions on the double
      diffusive free convective flow of a nanofluid along a semi-infinite flat solid
      vertical plate are investigated numerically. It is assumed that free stream is
      moving. The governing boundary layer equations are non-dimensionalized and
      transformed into a system of nonlinear, coupled similarity equations. The effects
      of the controlling parameters on the dimensionless velocity, temperature, solute
      and nanofluid concentration as well as on the reduced Nusselt number, reduced
      Sherwood number and the reduced nanoparticle Sherwood number are investigated and
      presented graphically. To the best of our knowledge, the effects of hydrodynamic
      and thermal slip boundary conditions have not been investigated yet. It is found
      that the reduced local Nusselt, local solute and the local nanofluid Sherwood
      numbers increase with hydrodynamic slip and decrease with thermal slip
      parameters.

PMID- 23533565
TI  - How often are ineffective interventions still used in clinical practice? A cross
      sectional survey of 6,272 clinicians in China.
AB  - BACKGROUND: The World Health Organization reported in 2011 that irrational use of
      medicines was a serious global problem that is wasteful and harmful. The worst is
      use of ineffective or harmful interventions which should not be used at all.
      However, little is known about the changes that 20 years of evidence-based
      medicine has made particularly in reducing use of ineffective interventions. We
      surveyed clinicians in China to show how often ineffective interventions were
      still used in practice. METHODS: 3,246 clinicians from 24 tertiary hospitals were
      surveyed in person and another 3,063 through an online survey between 2006-2007.
      The main outcomes are prescription by a clinician, and use in a patient of, an
      ineffective intervention and of a matched effective intervention in patients with
      the same disease. 129 ineffective interventions for 68 diseases were identified
      from the BMJ Clinical Evidence and included in the survey. One effective
      intervention was identified for each disease and a total of 68 effective
      interventions were thus also included. The frequency of use of effective
      interventions was used as a reference for that of ineffective intervention.
      RESULTS: The mean prescription rate by clinicians is 59.0% (95% confidence
      interval (95% CI): 58.6% to 59.4%) and 81.0% (95% CI: 80.6% to 81.4%)
      respectively for ineffective and effective interventions. The mean frequency of
      use in patients is 31.2% (95% CI: 30.8% to 31.6%) and 56.4% (95% CI: 56.0% to
      56.8%) for ineffective and effective interventions respectively. The relative
      reduction in use of ineffective interventions as compared with that of matched
      effective interventions is 27.2% (95% CI: 27.0% to 27.4%) and 44.7% (95% CI:
      44.3% to 45.1%) for clinician's prescription and use in patients respectively.
      8.6% ineffective interventions were still routinely used in practice.
      CONCLUSIONS: Ineffective interventions were still commonly used. Efforts are
      necessary to further reduce and eventually eliminate ineffective interventions
      from practice.

PMID- 23533567
TI  - Role of the phosphatase PTEN in early vascular remodeling.
AB  - BACKGROUND: The phosphatase PTEN represents an important physiological inhibitor
      of phosphatidylinositol-3 kinase (PI3-K)/protein kinase B (Akt) signalling,
      however, the functional role of PTEN in the initial phase of angioplasty-induced
      vascular injury remains elusive. In the present study we sought to determine
      PTEN's effect on vascular smooth muscle cell (VSMC) apoptosis following acute
      injury in vivo and in vitro. METHODS AND RESULTS: Immunohistochemistry indicated
      a faint basal expression and equal distribution of PTEN in uninjured rat carotid
      arteries. 12 h following balloon-injury, PTEN expression was strongly increased
      in apoptotic (TUNEL+) VSMC. In vitro, stimulation with serum or different growth
      factors or subjecting VSMC to cyclic stretch had no effect on PTEN expression,
      whereas stimulation with H2O2 robustly increased PTEN expression in a time- and
      dose-dependent manner. To evaluate the functional role of PTEN expression, human
      VSMC were transduced with WT-PTEN. Overexpression of PTEN increased the number of
      apoptotic VSMC (19.8%+/-4.4 vs. 5.6%+/-2.3; P<0.001) as determined by TUNEL
      assay. In contrast, siRNA-mediated knock-down of PTEN attenuated the basal as
      well as H2O2-induced apoptosis of VSMC. Mechanistically, overexpression of PTEN
      prevented serum-induced Akt-phosphorylation, whereas siRNA-mediated knock down of
      PTEN augmented Akt-activation. Moreover, co-transfection of PTEN and a
      constitutive active Akt mutant prevented PTEN-dependent augmentation of VSMC
      apoptosis, indicating, that PTEN regulates VSMC apoptosis by inhibition of Akt
      phosphorylation/activation. CONCLUSION: By interfering with the PI3-K/Akt
      dependent survival signalling, the oxidative stress-induced up regulation of PTEN
      in VSMC of injured arteries augments the sensitivity of VSMC to apoptotic stimuli
      in the early phase following vascular injury, augmenting the initial injury and
      cell loss of the injured vessel wall. Thus, these data add to our understanding
      of PTEN's role during vascular remodelling.

PMID- 23533568
TI  - Expression of fibroblast growth factor-21 in muscle is associated with
      lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
AB  - BACKGROUND: Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and
      lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found
      in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well
      understood. Patients with HIV-infection and lipodystrophy are characterised by
      various degree of lipid-driven insulin resistance. We hypothesized that muscle
      FGF-21 mRNA would be altered in HIV patients with lipodystrophy. DESIGN: Twenty
      five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy
      controls, received an oral glucose tolerance test and a euglycemic
      hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion.
      Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity
      were measured. RESULTS: Subjects with HIV were insulin resistant compared with
      non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold
      increase of plasma FGF-21 from 70.4+/-56.8 pg/ml vs 109.1+/-71.8 pg/ml,
      respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA
      expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of
      disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009), and the GS
      fractional velocity in muscle (r = -0.39, p = 0.03), and directly with fasting
      insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r =
      0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (
      0.46, p = 0.004), but not to plasma FGF-21. CONCLUSION: FGF-21 mRNA is increased
      in skeletal muscle in HIV patients and correlates to whole-body (primarily
      reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings
      add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21
      is working in a local manner.

PMID- 23533569
TI  - SHRINE: enabling nationally scalable multi-site disease studies.
AB  - Results of medical research studies are often contradictory or cannot be
      reproduced. One reason is that there may not be enough patient subjects available
      for observation for a long enough time period. Another reason is that patient
      populations may vary considerably with respect to geographic and demographic
      boundaries thus limiting how broadly the results apply. Even when similar patient
      populations are pooled together from multiple locations, differences in medical
      treatment and record systems can limit which outcome measures can be commonly
      analyzed. In total, these differences in medical research settings can lead to
      differing conclusions or can even prevent some studies from starting. We thus
      sought to create a patient research system that could aggregate as many patient
      observations as possible from a large number of hospitals in a uniform way. We
      call this system the 'Shared Health Research Information Network', with the
      following properties: (1) reuse electronic health data from everyday clinical
      care for research purposes, (2) respect patient privacy and hospital autonomy,
      (3) aggregate patient populations across many hospitals to achieve statistically
      significant sample sizes that can be validated independently of a single research
      setting, (4) harmonize the observation facts recorded at each institution such
      that queries can be made across many hospitals in parallel, (5) scale to regional
      and national collaborations. The purpose of this report is to provide open source
      software for multi-site clinical studies and to report on early uses of this
      application. At this time SHRINE implementations have been used for multi-site
      studies of autism co-morbidity, juvenile idiopathic arthritis, peripartum
      cardiomyopathy, colorectal cancer, diabetes, and others. The wide range of study
      objectives and growing adoption suggest that SHRINE may be applicable beyond the
      research uses and participating hospitals named in this report.

PMID- 23533570
TI  - Chordoma characterization of significant changes of the DNA methylation pattern.
AB  - Chordomas are rare mesenchymal tumors occurring exclusively in the midline from
      clivus to sacrum. Early tumor detection is extremely important as these tumors
      are resistant to chemotherapy and irradiation. Despite continuous research
      efforts surgical excision remains the main treatment option. Because of the often
      challenging anatomic location early detection is important to enable complete
      tumor resection and to reduce the high incidence of local recurrences. The aim of
      this study was to explore whether DNA methylation, a well known epigenetic
      marker, may play a role in chordoma development and if hypermethylation of
      specific CpG islands may serve as potential biomarkers correlated with SNP
      analyses in chordoma. The study was performed on tumor samples from ten chordoma
      patients. We found significant genomic instability by Affymetrix 6.0. It was
      interesting to see that all chordomas showed a loss of 3q26.32 (PIK 3CA) and
      3q27.3 (BCL6) thus underlining the potential importance of the PI3K pathway in
      chordoma development. By using the AITCpG360 methylation assay we elucidated 20
      genes which were hyper/hypomethylated compared to normal blood. The most
      promising candidates were nine hyper/hypomethylated genes C3, XIST, TACSTD2,
      FMR1, HIC1, RARB, DLEC1, KL, and RASSF1. In summary, we have shown that chordomas
      are characterized by a significant genomic instability and furthermore we
      demonstrated a characteristic DNA methylation pattern. These findings add new
      insights into chordoma development, diagnosis and potential new treatment
      options.

PMID- 23533571
TI  - Multi-allelic major effect genes interact with minor effect QTLs to control
      adaptive color pattern variation in Heliconius erato.
AB  - Recent studies indicate that relatively few genomic regions are repeatedly
      involved in the evolution of Heliconius butterfly wing patterns. Although this
      work demonstrates a number of cases where homologous loci underlie both
      convergent and divergent wing pattern change among different Heliconius species,
      it is still unclear exactly how many loci underlie pattern variation across the
      genus. To address this question for Heliconius erato, we created fifteen
      independent crosses utilizing the four most distinct color pattern races and
      analyzed color pattern segregation across a total of 1271 F2 and backcross
      offspring. Additionally, we used the most variable brood, an F2 cross between H.
      himera and the east Ecuadorian H. erato notabilis, to perform a quantitative
      genetic analysis of color pattern variation and produce a detailed map of the
      loci likely involved in the H. erato color pattern radiation. Using AFLP and gene
      based markers, we show that fewer major genes than previously envisioned control
      the color pattern variation in H. erato. We describe for the first time the
      genetic architecture of H. erato wing color pattern by assessing quantitative
      variation in addition to traditional linkage mapping. In particular, our data
      suggest three genomic intervals modulate the bulk of the observed variation in
      color. Furthermore, we also identify several modifier loci of moderate effect
      size that contribute to the quantitative wing pattern variation. Our results are
      consistent with the two-step model for the evolution of mimetic wing patterns in
      Heliconius and support a growing body of empirical data demonstrating the
      importance of major effect loci in adaptive change.

PMID- 23533572
TI  - Differential denaturation of serum proteome reveals a significant amount of
      hidden information in complex mixtures of proteins.
AB  - Recently developed proteomic technologies allow to profile thousands of proteins
      within a high-throughput approach towards biomarker discovery, although results
      are not as satisfactory as expected. In the present study we demonstrate that
      serum proteome denaturation is a key underestimated feature; in fact, a new
      differential denaturation protocol better discriminates serum proteins according
      to their electrophoretic mobility as compared to single-denaturation protocols.
      Sixty nine different denaturation treatments were tested and the 3 most
      discriminating ones were selected (TRIDENT analysis) and applied to human sera,
      showing a significant improvement of serum protein discrimination as confirmed by
      MALDI-TOF/MS and LC-MS/MS identification, depending on the type of denaturation
      applied. Thereafter sera from mice and patients carrying cutaneous melanoma were
      analyzed through TRIDENT. Nine and 8 protein bands were found differentially
      expressed in mice and human melanoma sera, compared to healthy controls (p<0.05);
      three of them were found, for the first time, significantly modulated:
      alpha2macroglobulin (down-regulated in melanoma, p<0.001), Apolipoprotein-E and
      Apolipoprotein-A1 (both up-regulated in melanoma, p<0.04), both in mice and
      humans. The modulation was confirmed by immunological methods. Other less
      abundant proteins (e.g. gelsolin) were found significantly modulated (p<0.05).
      CONCLUSIONS: i) serum proteome contains a large amount of information, still
      neglected, related to proteins folding; ii) a careful serum denaturation may
      significantly improve analytical procedures involving complex protein mixtures;
      iii) serum differential denaturation protocol highlights interesting proteomic
      differences between cancer and healthy sera.

PMID- 23533573
TI  - Integrated proteomics and metabolomics of Arabidopsis acclimation to gene-dosage
      dependent perturbation of isopropylmalate dehydrogenases.
AB  - Maintaining metabolic homeostasis is critical for plant growth and development.
      Here we report proteome and metabolome changes when the metabolic homeostasis is
      perturbed due to gene-dosage dependent mutation of Arabidopsis isopropylmalate
      dehydrogenases (IPMDHs). By integrating complementary quantitative proteomics and
      metabolomics approaches, we discovered that gradual ablation of the oxidative
      decarboxylation step in leucine biosynthesis caused imbalance of amino acid
      homeostasis, redox changes and oxidative stress, increased protein synthesis, as
      well as a decline in photosynthesis, which led to rearrangement of central
      metabolism and growth retardation. Disruption of IPMDHs involved in aliphatic
      glucosinolate biosynthesis led to synchronized increase of both upstream and
      downstream biosynthetic enzymes, and concomitant repression of the degradation
      pathway, indicating metabolic regulatory mechanisms in controlling glucosinolate
      biosynthesis.

PMID- 23533574
TI  - SjAPI, the first functionally characterized Ascaris-type protease inhibitor from
      animal venoms.
AB  - BACKGROUND: Serine protease inhibitors act as modulators of serine proteases,
      playing important roles in protecting animal toxin peptides from degradation.
      However, all known serine protease inhibitors discovered thus far from animal
      venom belong to the Kunitz-type subfamily, and whether there are other novel
      types of protease inhibitors in animal venom remains unclear. PRINCIPAL FINDINGS:
      Here, by screening scorpion venom gland cDNA libraries, we identified the first
      Ascaris-type animal toxin family, which contains four members: Scorpiops jendeki
      Ascaris-type protease inhibitor (SjAPI), Scorpiops jendeki Ascaris-type protease
      inhibitor 2 (SjAPI-2), Chaerilus tricostatus Ascaris-type protease inhibitor
      (CtAPI), and Buthus martensii Ascaris-type protease inhibitor (BmAPI). The
      detailed characterization of Ascaris-type peptide SjAPI from the venom gland of
      scorpion Scorpiops jendeki was carried out. The mature peptide of SjAPI contains
      64 residues and possesses a classical Ascaris-type cysteine framework reticulated
      by five disulfide bridges, different from all known protease inhibitors from
      venomous animals. Enzyme and inhibitor reaction kinetics experiments showed that
      recombinant SjAPI was a dual function peptide with alpha-chymotrypsin- and
      elastase-inhibiting properties. Recombinant SjAPI inhibited alpha-chymotrypsin
      with a Ki of 97.1 nM and elastase with a Ki of 3.7 MUM, respectively.
      Bioinformatics analyses and chimera experiments indicated that SjAPI contained
      the unique short side chain functional residues "AAV" and might be a useful
      template to produce new serine protease inhibitors. CONCLUSIONS/SIGNIFICANCE: To
      our knowledge, SjAPI is the first functionally characterized animal toxin peptide
      with an Ascaris-type fold. The structural and functional diversity of animal
      toxins with protease-inhibiting properties suggested that bioactive peptides from
      animal venom glands might be a new source of protease inhibitors, which will
      accelerate the development of diagnostic and therapeutic agents for human
      diseases that target diverse proteases.

PMID- 23533575
TI  - Intramyocardial transplantation and tracking of human mesenchymal stem cells in a
      novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof
      of concept study.
AB  - Although stem-cell therapies have been suggested for cardiac-regeneration after
      myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain
      unknown. While most available animal-models require immunosuppressive-therapy
      when applying human cells, the fetal-sheep being pre-immune until day 75 of
      gestation has been proposed for the in-vivo tracking of human cells after intra
      peritoneal transplantation. We introduce a novel intra-uterine myocardial
      infarction model to track human mesenchymal stem cells after direct intra
      myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep
      (gestation age: 70-75 days) were included. Ten animals either received an intra
      uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6)
      using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either
      derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3).
      Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n =
      2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9
      days. To assess human cell-fate, multimodal cell-tracking was performed via MRI
      and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI
      displayed an estimated amount of 1*10(5)-5*10(5) human cells within ventricular
      wall corresponding to the injection-sites which was further confirmed on Micro
      CT. PCR and IHC verified intra-myocardial presence via detection of human
      specific beta-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the
      fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and
      were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed
      intra-myocardial presence, and showed further distribution within the spleen,
      lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra
      peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the
      cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal
      lavage, but not within the heart. For the first time we demonstrate the
      feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the
      pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising
      advanced imaging-technologies and in-vitro tracking-tools, this novel model may
      serve as a unique platform to assess human cell-fate after intra-myocardial
      transplantation without the necessity of immunosuppressive-therapy.

PMID- 23533576
TI  - Rule-based model of vein graft remodeling.
AB  - When vein segments are implanted into the arterial system for use in arterial
      bypass grafting, adaptation to the higher pressure and flow of the arterial
      system is accomplished thorough wall thickening and expansion. These early
      remodeling events have been found to be closely coupled to the local hemodynamic
      forces, such as shear stress and wall tension, and are believed to be the
      foundation for later vein graft failure. To further our mechanistic understanding
      of the cellular and extracellular interactions that lead to global changes in
      tissue architecture, a rule-based modeling method is developed through the
      application of basic rules of behaviors for these molecular and cellular
      activities. In the current method, smooth muscle cell (SMC), extracellular matrix
      (ECM), and monocytes are selected as the three components that occupy the
      elements of a grid system that comprise the developing vein graft intima. The
      probabilities of the cellular behaviors are developed based on data extracted
      from in vivo experiments. At each time step, the various probabilities are
      computed and applied to the SMC and ECM elements to determine their next physical
      state and behavior. One- and two-dimensional models are developed to test and
      validate the computational approach. The importance of monocyte infiltration, and
      the associated effect in augmenting extracellular matrix deposition, was
      evaluated and found to be an important component in model development. Final
      model validation is performed using an independent set of experiments, where
      model predictions of intimal growth are evaluated against experimental data
      obtained from the complex geometry and shear stress patterns offered by a mid
      graft focal stenosis, where simulation results show good agreements with the
      experimental data.

PMID- 23533577
TI  - Redox-sensitive up-regulation of eNOS by purple grape juice in endothelial cells:
      role of PI3-kinase/Akt, p38 MAPK, JNK, FoxO1 and FoxO3a.
AB  - The vascular protective effect of grape-derived polyphenols has been
      attributable, in part, to their direct action on blood vessels by stimulating the
      endothelial formation of nitric oxide (NO). The aim of the present study was to
      determine whether Concord grape juice (CGJ), which contains high levels of
      polyphenols, stimulates the expression of endothelial NO synthase (eNOS) in
      porcine coronary artery endothelial cells and, if so, to determine the signaling
      pathway involved. CGJ dose- and time-dependently increased eNOS mRNA and protein
      levels and this effect is associated with an increased formation of NO in
      endothelial cells. The stimulatory effect of CGJ on eNOS mRNA is not associated
      with an increased eNOS mRNA stability and inhibited by antioxidants such as
      MnTMPyP, PEG-catalase, and catalase, and by wortmannin (an inhibitor of PI3
      kinase), SB 203580 (an inhibitor of p38 MAPK), and SP 600125 (an inhibitor of
      JNK). Moreover, CGJ induced the formation of reactive oxygen species (ROS) in
      endothelial cells and this effect is inhibited by MnTMPyP, PEG-catalase, and
      catalase. The CGJ-induced the phosphorylation of p38 MAPK and JNK kinases is
      abolished by MnTMPyP. CGJ induced phosphorylation of transcription factors FoxO1
      and FoxO3a, which regulate negatively eNOS expression, and this effect is
      prevented by MnTMPyP, PEG-catalase, wortmannin, SB203580 and SP600125. Moreover,
      chromatin immunoprecipitation assay indicated that the FoxO3a protein is
      associated with the eNOS promoter in control cells and that CGJ induced its
      dissociation. Thus, the present study indicates that CGJ up-regulates the
      expression of eNOS mRNA and protein leading to an increased formation of NO in
      endothelial cells. The stimulatory effect of CGJ is a redox-sensitive event
      involving PI3-kinase/Akt, p38 MAPK and JNK pathways, and the inactivation of the
      FoxO transcription factors, FoxO1 and FoxO3a, thereby preventing their repression
      of the eNOS gene.

PMID- 23533578
TI  - Observational study of vaccine efficacy 24 years after the start of hepatitis B
      vaccination in two Gambian villages: no need for a booster dose.
AB  - OBJECTIVES: To determine the duration of protection from hepatitis B vaccine
      given in infancy and early childhood and asses risk factors for HBV infection and
      chronic infection. METHODS: In 1984 infant HBV vaccination was started in two
      Gambian villages. Cross sectional serological surveys have been undertaken every
      4 years to determine vaccine efficacy. In the current survey 84.6% of 1508
      eligible participants aged 1-28 years were tested. A spouse study was conducted
      in females (aged 14 years and above) and their male partners. RESULTS: Vaccine
      efficacy against chronic infection with hepatitis B virus was 95.1% (95%
      confidence interval 91.5% to 97.1%), which did not vary significantly between age
      groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%), falling
      significantly with age. Concentrations of hepatitis B antibody fell exponentially
      with age varying according to peak response: 20 years after vaccination only
      17.8% (95% CI 10.1-25.6) of persons with a low peak response (10-99 mIU/ml) had
      detectable HBs antibody compared to 27% (21.9% to 32.2%) of those with a high
      peak response (>999 mIU/ml). Time since vaccination and a low peak response were
      the strongest risk factors for HBV infections; males were more susceptible,
      marriage was not a significant risk for females. Hepatitis B DNA was not detected
      after infection, which tested soley core antibody positive. An undetectable peak
      antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen
      positive were powerful risk factors for chronic infection. CONCLUSIONS:
      Adolescents and young adults vaccinated in infancy are at increased risk of
      hepatitis B infection, but not chronic infection. Married women were not at
      increased risk. There is no compelling evidence for the use of a booster dose of
      HBV vaccine in The Gambia.

PMID- 23533579
TI  - Three phases of CD8 T cell response in the lung following H1N1 influenza
      infection and sphingosine 1 phosphate agonist therapy.
AB  - Influenza-induced lung edema and inflammation are exacerbated by a positive
      feedback loop of cytokine and chemokine production termed a 'cytokine storm', a
      hallmark of increased influenza-related morbidity and mortality. Upon infection,
      an immune response is rapidly initiated in the lungs and draining lymph node,
      leading to expansion of virus-specific effector cells. Using two-photon
      microscopy, we imaged the dynamics of dendritic cells (DC) and virus-specific
      eGFP(+)CD8(+) T cells in the lungs and draining mediastinal lymph nodes during
      the first two weeks following influenza infection. Three distinct phases of T
      cell and CD11c(+) DC behavior were revealed: 1) Priming, facilitated by the
      arrival of lung DCs in the lymph node and characterized by antigen recognition
      and expansion of antigen-specific CD8(+) T cells; asymmetric T cell division in
      contact with DCs was frequently observed. 2) Clearance, during which DCs re
      populate the lung and T cells leave the draining lymph node and re-enter the lung
      tissue where enlarged, motile T cells come into contact with DCs and form long
      lived interactions. 3) Maintenance, characterized by T-cell scanning of the lung
      tissue and dissociation from local antigen presenting cells; the T cells spend
      less time in association with DCs and migrate rapidly on collagen. A single dose
      of a sphingosine-1-phosphate receptor agonist, AAL-R, sufficient to suppress
      influenza-induced cytokine-storm, altered T cell and DC behavior during influenza
      clearance, delaying T cell division, cellular infiltration in the lung, and
      suppressing T-DC interactions in the lung. Our results provide a detailed
      description of T cell and DC choreography and dynamics in the lymph node and the
      lung during influenza infection. In addition, we suggest that phase lags in T
      cell and DC dynamics induced by targeting S1P receptors in vivo may attenuate the
      intensity of the immune response and can be manipulated for therapeutic benefit.

PMID- 23533580
TI  - SNP discovery and chromosome anchoring provide the first physically-anchored
      hexaploid oat map and reveal synteny with model species.
AB  - A physically anchored consensus map is foundational to modern genomics research;
      however, construction of such a map in oat (Avena sativa L., 2n = 6x = 42) has
      been hindered by the size and complexity of the genome, the scarcity of robust
      molecular markers, and the lack of aneuploid stocks. Resources developed in this
      study include a modified SNP discovery method for complex genomes, a diverse set
      of oat SNP markers, and a novel chromosome-deficient SNP anchoring strategy.
      These resources were applied to build the first complete, physically-anchored
      consensus map of hexaploid oat. Approximately 11,000 high-confidence in silico
      SNPs were discovered based on nine million inter-varietal sequence reads of
      genomic and cDNA origin. GoldenGate genotyping of 3,072 SNP assays yielded 1,311
      robust markers, of which 985 were mapped in 390 recombinant-inbred lines from six
      bi-parental mapping populations ranging in size from 49 to 97 progeny. The
      consensus map included 985 SNPs and 68 previously-published markers, resolving 21
      linkage groups with a total map distance of 1,838.8 cM. Consensus linkage groups
      were assigned to 21 chromosomes using SNP deletion analysis of chromosome
      deficient monosomic hybrid stocks. Alignments with sequenced genomes of rice and
      Brachypodium provide evidence for extensive conservation of genomic regions, and
      renewed encouragement for orthology-based genomic discovery in this important
      hexaploid species. These results also provide a framework for high-resolution
      genetic analysis in oat, and a model for marker development and map construction
      in other species with complex genomes and limited resources.

PMID- 23533581
TI  - Involvement of DNA-PKcs in the IL-6 and IL-12 response to CpG-ODN is mediated by
      its interaction with TRAF6 in dendritic cells.
AB  - CpG-ODN stimulates dendritic cells (DCs) to produce cytokines, which are
      important for pathogenesis of autoimmune disorders and vaccine strategy for
      cancer. CpG-ODN activates the TLR9/MyD88/TRAF6 cascade leading to activation of
      IKK-NF-kappaB and JNK, which are critical for production of pro-inflammatory
      cytokines. However, whether other molecules are involved in activation of CpG-ODN
      signaling is still not clear. Here we report that the catalytic subunit of DNA
      dependent protein kinase (DNA-PKcs) is involved in this activation process. DNA
      PKcs-deficient DCs exhibited a defect in the IL-6 and IL-12 response to CpG-ODN
      in a dose- and time-dependent manner. Loss of DNA-PKcs impaired phosphorylation
      of IKK, IkappaBalpha, NF-kappaB and JNK in response to CpG-ODN. Interestingly,
      CpG-ODN was able to bind DNA-PKcs and induce its association and co-localization
      with TRAF6 in the absence of TLR9. Our data suggest that DNA-PKcs is a player in
      CpG-ODN signaling and may explain why DNA-PKcs is implicated in the pathogenic
      process of autoimmune disease.

PMID- 23533582
TI  - Human chemokines as antimicrobial peptides with direct parasiticidal effect on
      Leishmania mexicana in vitro.
AB  - Chemokines and chemokine receptor-mediated effects are important mediators of the
      immunological response and cure in human leishmaniasis. However, in addition to
      their signalling properties for leukocytes, many chemokines have also been shown
      to act directly as antimicrobial peptides on bacteria and fungi. We screened ten
      human chemokines (CXCL2, CXCL6, CXCL8, CXCL9, CXCL10, CCL2, CCL3, CCL20, CCL27,
      CCL28) for antimicrobial effects on the promastigote form of the protozoan
      parasite Leishmania mexicana, and observed direct parasiticidal effects of
      several, CCL28 being the most potent. Damage to the plasma membrane integrity
      could be visualised by entrance of propidium iodide, as measured with flow
      cytometry, and by scanning electron microscopy, which showed morphological
      changes and aggregation of cells. The findings were in concordance with
      parasiticidal activity, measured by decreased mitochondrial activity in an MTT
      assay. This is the first report of direct antimicrobial activity by chemokines on
      parasites. This component of immunity against Leishmania parasites identified
      here warrants further investigation that might lead to new insight in the
      mechanisms of human infection and/or new therapeutic approaches.

PMID- 23533583
TI  - DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping
      and differentiation.
AB  - DiGeorge syndrome (DGS) is the most common microdeletion syndrome, and is
      characterized by congenital cardiac, craniofacial and immune system
      abnormalities. The cardiac defects in DGS patients include conotruncal and
      ventricular septal defects. Although the etiology of DGS is critically regulated
      by TBX1 gene, the molecular pathways underpinning TBX1's role in heart
      development are not fully understood. In this study, we characterized heart
      defects and downstream signaling in the zebrafish tbx1(-/-) mutant, which has
      craniofacial and immune defects similar to DGS patients. We show that tbx1(-/-)
      mutants have defective heart looping, morphology and function. Defective heart
      looping is accompanied by failure of cardiomyocytes to differentiate normally and
      failure to change shape from isotropic to anisotropic morphology in the outer
      curvatures of the heart. This is the first demonstration of tbx1's role in
      regulating heart looping, cardiomyocyte shape and differentiation, and may
      explain how Tbx1 regulates conotruncal development in humans. Next we elucidated
      tbx1's molecular signaling pathway guided by the cardiac phenotype of tbx1(-/-)
      mutants. We show for the first time that wnt11r (wnt11 related), a member of the
      non-canonical Wnt pathway, and its downstream effector gene alcama (activated
      leukocyte cell adhesion molecule a) regulate heart looping and differentiation
      similarly to tbx1. Expression of both wnt11r and alcama are downregulated in
      tbx1(-/-) mutants. In addition, both wnt11r (-/-) mutants and alcama morphants
      have heart looping and differentiation defects similar to tbx1(-/-) mutants.
      Strikingly, heart looping and differentiation in tbx1(-/-) mutants can be
      partially rescued by ectopic expression of wnt11r or alcama, supporting a model
      whereby heart looping and differentiation are regulated by tbx1 in a linear
      pathway through wnt11r and alcama. This is the first study linking tbx1 and non
      canonical Wnt signaling and extends our understanding of DGS and heart
      development.

PMID- 23533584
TI  - Effects of C-phycocyanin and Spirulina on salicylate-induced tinnitus, expression
      of NMDA receptor and inflammatory genes.
AB  - Effects of C-phycocyanin (C-PC), the active component of Spirulina platensis
      water extract on the expressions of N-methyl D-aspartate receptor subunit 2B
      (NR2B), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      and cyclooxygenase type 2 (COX-2) genes in the cochlea and inferior colliculus
      (IC) of mice were evaluated after tinnitus was induced by intraperitoneal
      injection of salicylate. The results showed that 4-day salicylate treatment
      (unlike 4-day saline treatment) caused a significant increase in NR2B, TNF-alpha,
      and IL-1beta mRNAs expression in the cochlea and IC. On the other hand, dietary
      supplementation with C-PC or Spirulina platensis water extract significantly
      reduced the salicylate-induced tinnitus and down-regulated the mRNAs expression
      of NR2B, TNF-alpha, IL-1beta mRNAs, and COX-2 genes in the cochlea and IC of
      mice. The changes of protein expression levels were generally correlated with
      those of mRNAs expression levels in the IC for above genes.

PMID- 23533585
TI  - beta-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and
      Mg2+ regulation.
AB  - Here we investigate how beta-adrenergic stimulation of the heart alters
      regulation of ryanodine receptors (RyRs) by intracellular Ca(2+) and Mg(2+) and
      the role of these changes in SR Ca(2+) release. RyRs were isolated from rat
      hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min
      perfusion with 1 uM isoproterenol or without (control) and snap frozen in liquid
      N2 to capture their phosphorylation state. Western Blots show that RyR2
      phosphorylation was increased by isoproterenol, confirming that RyR2 were subject
      to normal beta-adrenergic signaling. Under basal conditions, S2808 and S2814 had
      phosphorylation levels of 69% and 15%, respectively. These levels were increased
      to 83% and 60%, respectively, after 60 s of beta-adrenergic stimulation
      consistent with other reports that beta-adrenergic stimulation of the heart can
      phosphorylate RyRs at specific residues including S2808 and S2814 causing an
      increase in RyR activity. At cytoplasmic [Ca(2+)] <1 uM, beta-adrenergic
      stimulation increased luminal Ca(2+) activation of single RyR channels, decreased
      luminal Mg(2+) inhibition and decreased inhibition of RyRs by mM cytoplasmic
      Mg(2+). At cytoplasmic [Ca(2+)] >1 uM, beta-adrenergic stimulation only decreased
      cytoplasmic Mg(2+) and Ca(2+) inhibition of RyRs. The Ka and maximum levels of
      cytoplasmic Ca(2+) activation site were not affected by beta-adrenergic
      stimulation. Our RyR2 gating model was fitted to the single channel data. It
      predicted that in diastole, beta-adrenergic stimulation is mediated by 1)
      increasing the activating potency of Ca(2+) binding to the luminal Ca(2+) site
      and decreasing its affinity for luminal Mg(2+) and 2) decreasing affinity of the
      low-affinity Ca(2+)/Mg(2+) cytoplasmic inhibition site. However in systole, beta
      adrenergic stimulation is mediated mainly by the latter.

PMID- 23533586
TI  - Reduced fronto-temporal and limbic connectivity in the 22q11.2 deletion syndrome:
      vulnerability markers for developing schizophrenia?
AB  - The 22q11.2 deletion syndrome (22q11DS) is a widely recognized genetic model
      allowing the study of neuroanatomical biomarkers that underlie the risk for
      developing schizophrenia. Recent advances in magnetic resonance image analyses
      enable the examination of structural connectivity integrity, scarcely used in the
      22q11DS field. This framework potentially provides evidence for the
      disconnectivity hypothesis of schizophrenia in this high-risk population. In the
      present study, we quantify the whole brain white matter connections in 22q11DS
      using deterministic tractography. Diffusion Tensor Imaging was acquired in 30
      affected patients and 30 age- and gender-matched healthy participants. The Human
      Connectome technique was applied to register white matter streamlines with
      cortical anatomy. The number of fibers (streamlines) was used as a measure of
      connectivity for comparison between groups at the global, lobar and regional
      level. All statistics were corrected for age and gender. Results showed a 10%
      reduction of the total number of fibers in patients compared to controls. After
      correcting for this global reduction, preserved connectivity was found within the
      right frontal and right parietal lobes. The relative increase in the number of
      fibers was located mainly in the right hemisphere. Conversely, an excessive
      reduction of connectivity was observed within and between limbic structures.
      Finally, a disproportionate reduction was shown at the level of fibers connecting
      the left fronto-temporal regions. We could therefore speculate that the observed
      disruption to fronto-temporal connectivity in individuals at risk of
      schizophrenia implies that fronto-temporal disconnectivity, frequently implicated
      in the pathogenesis of schizophrenia, could precede the onset of symptoms and, as
      such, constitutes a biomarker of the vulnerability to develop psychosis. On the
      contrary, connectivity alterations in the limbic lobe play a role in a wide range
      of psychiatric disorders and therefore seem to be less specific in defining
      schizophrenia.

PMID- 23533587
TI  - Effect of circadian phase on memory acquisition and recall: operant conditioning
      vs. classical conditioning.
AB  - There have been several studies on the role of circadian clocks in the regulation
      of associative learning and memory processes in both vertebrate and invertebrate
      species. The results have been quite variable and at present it is unclear to
      what extent the variability observed reflects species differences or differences
      in methodology. Previous results have shown that following differential classical
      conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination
      task, formation of the short-term and long-term memory is under strict circadian
      control. In contrast, there appeared to be no circadian regulation of the ability
      to recall established memories. In the present study, we show that following
      operant conditioning of the same species in a very similar olfactory
      discrimination task, there is no impact of the circadian system on either short
      term or long-term memory formation. On the other hand, ability to recall
      established memories is strongly tied to the circadian phase of training. On the
      basis of these data and those previously reported for phylogenetically diverse
      species, it is suggested that there may be fundamental differences in the way the
      circadian system regulates learning and memory in classical and operant
      conditioning.

PMID- 23533588
TI  - Rapid high-level production of functional HIV broadly neutralizing monoclonal
      antibodies in transient plant expression systems.
AB  - Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies
      (mAbs) has shown promise as an HIV treatment, reducing mother-to-child
      transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human
      primates and decreasing viral rebound in patients who ceased receiving anti-viral
      drugs. In addition, a cocktail of potent mAbs may be useful as mucosal
      microbicides and provide an effective therapy for post-exposure prophylaxis.
      However, even highly neutralizing HIV mAbs used today may lose their
      effectiveness if resistance occurs, requiring the rapid production of new or
      engineered mAbs on an ongoing basis in order to counteract the viral resistance
      or the spread of a certain HIV-1 clade in a particular region or patient. Plant
      based expression systems are fast, inexpensive and scalable and are becoming
      increasingly popular for the production of proteins and monoclonal antibodies. In
      the present study, Agrobacterium-mediated transient transfection of plants,
      utilizing two species of Nicotiana, have been tested to rapidly produce high
      levels of an HIV 89.6PDelta140env and several well-studied anti-HIV neutralizing
      monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain
      antibody construct (m9), for evaluation in cell-based viral inhibition assays.
      The protein-A purified plant-derived antibodies were intact, efficiently bound
      HIV envelope, and were equivalent to, or in one case better than, their
      counterparts produced in mammalian CHO or HEK-293 cells in both neutralization
      and antibody dependent viral inhibition assays. These data indicate that
      transient plant-based transient expression systems are very adaptable and could
      rapidly generate high levels of newly identified functional recombinant HIV
      neutralizing antibodies when required. In addition, they warrant detailed cost
      benefit analysis of prolonged incubation in plants to further increase mAb
      production.

PMID- 23533589
TI  - Aminoglycoside-induced hair cell death of inner ear organs causes functional
      deficits in adult zebrafish (Danio rerio).
AB  - Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in
      a variety of species including chickens, mice, and humans. The zebrafish (Danio
      rerio) has been used to study hair cell cytotoxicity in the lateral line organs
      of larval and adult animals. Little is known about whether aminoglycosides kill
      the hair cells within the inner ear of adult zebrafish. We report here the
      ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing
      organ, and utricle of zebrafish. First, adult zebrafish received a single 30
      mg/kg intraperitoneal injection of fluorescently-tagged gentamicin (GTTR) to
      determine the distribution of gentamicin within inner ear sensory epithelia.
      After 4 hours, GTTR was observed in hair cells throughout the saccular and
      utriclar sensory epithelia. To assess the ototoxic effects of gentamicin, adult
      zebrafish received a single 250 mg/kg intraperitoneal injection of gentamicin
      and, 24 hours later, auditory evoked potential recordings (AEPs) revealed
      significant shifts in auditory thresholds compared to untreated controls.
      Zebrafish were then euthanized, the inner ear fixed, and labeled for apoptotic
      cells (TUNEL reaction), and the stereociliary bundles of hair cells labeled with
      fluorescently-tagged phalloidin. Whole mounts of the saccule and utricle were
      imaged and cells counted. There were significantly more TUNEL-labeled cells found
      in both organs 4 hours after gentamicin injection compared to vehicle-injected
      controls. As expected, significantly fewer hair cell bundles were found along the
      rostral-caudal axis of the saccule and in the extrastriolar and striolar regions
      of the utricle in gentamicin-treated animals compared to untreated controls.
      Therefore, as in other species, gentamicin causes significant inner ear sensory
      hair cell death and auditory dysfunction in zebrafish.

PMID- 23533590
TI  - A nonparametric procedure for defining a new humoral immunologic profile in a
      pilot study on HIV infected patients.
AB  - This work aims at identifying a set of humoral immunologic parameters that
      improve prediction of the activation process in HIV patients. Starting from the
      well-known impact of humoral immunity in HIV infection, there is still a lack of
      knowledge in defining the role of the modulation of functional activity and
      titers of serum antibodies from early stage of infection to the development of
      AIDS. We propose an integrated approach that combines humoral and clinical
      parameters in defining the host immunity, implementing algorithms associated with
      virus control. A number of humoral parameters were simultaneously evaluated in a
      whole range of serum samples from HIV-positive patients. This issue has been
      afforded accounting for estimation problems typically related to "feasibility"
      studies where small sample size in each group and large number of parameters are
      jointly estimated. We used nonparametric statistical procedures to identify
      biomarkers in our study which included 42 subjects stratified on five different
      stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors
      (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to
      illustrate a novel profiling method for helping to design a further confirmatory
      study. A set of seventeen different HIV-specific blood humoral factors were
      analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole
      gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope
      of the HR1 region and to CCR5; neutralization activity against five different
      virus strains and ADCC were also evaluated. Patients were selected on the basis
      of CD4 cell counts, HIV/RNA and clinical status. The Classification and
      Regression Trees (CART) approach has been used to uncover specific patterns of
      humoral parameters in different stages of HIV disease. Virus neutralization of
      primary virus strains and antibodies to gp41 were required to classify patients,
      suggesting that clinical profiles strongly rely on functional activity against
      HIV.

PMID- 23533591
TI  - Identification and prediction of diabetic sensorimotor polyneuropathy using
      individual and simple combinations of nerve conduction study parameters.
AB  - OBJECTIVE: Evaluation of diabetic sensorimotor polyneuropathy (DSP) is hindered
      by the need for complex nerve conduction study (NCS) protocols and lack of
      predictive biomarkers. We aimed to determine the performance of single and simple
      combinations of NCS parameters for identification and future prediction of DSP.
      MATERIALS AND METHODS: 406 participants (61 with type 1 diabetes and 345 with
      type 2 diabetes) with a broad spectrum of neuropathy, from none to severe,
      underwent NCS to determine presence or absence of DSP for cross-sectional
      (concurrent validity) analysis. The 109 participants without baseline DSP were re
      evaluated for its future onset (predictive validity). Performance of NCS
      parameters was compared by area under the receiver operating characteristic curve
      (AROC). RESULTS: At baseline there were 246 (60%) Prevalent Cases. After 3.9
      years mean follow-up, 25 (23%) of the 109 Prevalent Controls that were followed
      became Incident DSP Cases. Threshold values for peroneal conduction velocity and
      sural amplitude potential best identified Prevalent Cases (AROC 0.90 and 0.83,
      sensitivity 80 and 83%, specificity 89 and 72%, respectively). Baseline tibial F
      wave latency, peroneal conduction velocity and the sum of three lower limb nerve
      conduction velocities (sural, peroneal, and tibial) best predicted 4-year
      incidence (AROC 0.79, 0.79, and 0.85; sensitivity 79, 70, and 81%; specificity
      63, 74 and 77%, respectively). DISCUSSION: Individual NCS parameters or their
      simple combinations are valid measures for identification and future prediction
      of DSP. Further research into the predictive roles of tibial F-wave latencies,
      peroneal conduction velocity, and sum of conduction velocities as markers of
      incipient nerve injury is needed to risk-stratify individuals for clinical and
      research protocols.

PMID- 23533592
TI  - OstemiR: a novel panel of microRNA biomarkers in osteoblastic and osteocytic
      differentiation from mesencymal stem cells.
AB  - MicroRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate
      cell behavior through inhibition of translation from mRNA to protein, promotion
      of mRNA degradation and control of gene transcription. In this study, we
      investigated the miRNA expression signatures of cell cultures undergoing
      osteoblastic and osteocytic differentiation from mesenchymal stem cells (MSC)
      using mouse MSC line KUSA-A1 and human MSCs. Ninety types of miRNA were
      quantified during osteoblastic/osteocytic differentiation in KUSA-A1 cells
      utilizing miRNA PCR arrays. Coincidently with mRNA induction of the osteoblastic
      and osteocytic markers, the expression levels of several dozen miRNAs including
      miR-30 family, let-7 family, miR-21, miR-16, miR-155, miR-322 and Snord85 were
      changed during the differentiation process. These miRNAs were predicted to
      recognize osteogenic differentiation-, stemness-, epinegetics-, and cell cycle
      related mRNAs, and were thus designated OstemiR. Among those OstemiR, the miR-30
      family was classified into miR-30b/c and miR-30a/d/e groups on the basis of
      expression patterns during osteogenesis as well as mature miRNA structures. In
      silico prediction and subsequent qRT-PCR in stable miR-30d transfectants
      clarified that context-dependent targeting of miR-30d on known regulators of bone
      formation including osteopontin/spp1, lifr, ccn2/ctgf, ccn1/cyr61, runx2, sox9 as
      well as novel key factors including lin28a, hnrnpa3, hspa5/grp78, eed and pcgf5.
      In addition, knockdown of human OstemiR miR-541 increased Osteopontin/SPP1
      expression and calcification in hMSC osteoblastic differentiation, indicating
      that miR-541 is a negative regulator of osteoblastic differentiation. These
      observations indicate stage-specific roles of OstemiR especially miR-541 and the
      miR-30 family on novel targets in osteogenesis.

PMID- 23533593
TI  - Quantitative molecular analysis of sentinel lymph node may be predictive of
      axillary node status in breast cancer classified by molecular subtypes.
AB  - To determine the performance of intraoperative one-step nucleic acid
      amplification (OSNA) assay in detecting sentinel lymph node metastases compared
      to postoperative histology taking into account breast cancer molecular
      classification and to evaluate whether the level of cytokeratin 19 mRNA copy
      number may be useful in predicting the likelihood of a positive axillary lymph
      node dissection. OSNA assay was performed in a prospective series of 903
      consecutive sentinel lymph nodes from 709 breast cancer patients using 2
      alternate slices of each sentinel lymph node. The remaining 2 slices were
      investigated by histology. Cytokeratin 19 mRNA copy number, which distinguishes
      negative cases (<250 copies), micrometastases (+, >=250<=5000 copies) and
      macrometastases (++, >5000 copies), was compared to axillary lymph node
      dissection status and to the biological tumor profile. Concordance between OSNA
      and histopathology was 95%, specificity 95% and sensitivity 93%. Multiple
      Corresponce Analysis and logistic regression evidenced that positive axillary
      lymph node dissection was significantly associated with a higher cytokeratin 19
      mRNA copy number (>5000; p<0.0001), HER2 subtype (p = 0.007) and lymphovascular
      invasion (p<0.0001). Conversely, breast cancer patients with cytokeratin 19 mRNA
      copy number <2000 mostly presented a luminal subtype and a negative axillary
      lymph node dissection. We confirmed that OSNA assay can provide standardized and
      reproducible results and that it represents a fast and quantitative tool for
      intraoperative evaluation of sentinel lymph node. Omission of axillary lymph node
      dissection could be proposed in patients presenting a sentinel lymph node with a
      cytokeratin 19 mRNA copy number <2000 and a Luminal tumor phenotype.

PMID- 23533594
TI  - Wnt1 inhibits hydrogen peroxide-induced apoptosis in mouse cardiac stem cells.
AB  - BACKGROUND: Because of their regenerative and paracrine abilities, cardiac stem
      cells (CSCs) are the most appropriate, optimal and promising candidates for the
      development of cardiac regenerative medicine strategies. However, native and
      exogenous CSCs in ischemic hearts are exposed to various pro-apoptotic or
      cytotoxic factors preventing their regenerative and paracrine abilities. METHODS
      AND RESULTS: We examined the effects of H2O2 on mouse CSCs (mCSCs), and observed
      that hydrogen peroxide (H2O2) treatment induces mCSCs apoptosis via the caspase 3
      pathway, in a dose-dependent manner. We then examined the effects of Wnt1 over
      expression on H2O2-induced apoptosis in mCSCs and observed that Wnt1
      significantly decreased H2O2-induced apoptosis in mCSCs. On the other hand,
      inhibition of the canonical Wnt pathway by the secreted frizzled related protein
      2 (SFRP2) or knockdown of beta-catenin in mCSCs reduced cells resistance to H2O2
      induced apoptosis, suggesting that Wnt1 predominantly prevents H2O2-induced
      apoptosis through the canonical Wnt pathway. CONCLUSIONS: Our results provide the
      first evidences that Wnt1 plays an important role in CSCs' defenses against H2O2
      induced apoptosis through the canonical Wnt1/GSK3beta/beta-catenin signaling
      pathway.

PMID- 23533595
TI  - Cost-effectiveness analysis of risk-factor guided and birth-cohort screening for
      chronic hepatitis C infection in the United States.
AB  - BACKGROUND: No consensus exists on screening to detect the estimated 2 million
      Americans unaware of their chronic hepatitis C infections. Advisory groups
      differ, recommending birth-cohort screening for baby boomers, screening only high
      risk individuals, or no screening. We assessed one-time risk assessment and
      screening to identify previously undiagnosed 40-74 year-olds given newly
      available hepatitis C treatments. METHODS AND FINDINGS: A Markov model evaluated
      alternative risk-factor guided and birth-cohort screening and treatment
      strategies. Risk factors included drug use history, blood transfusion before
      1992, and multiple sexual partners. Analyses of the National Health and Nutrition
      Examination Survey provided sex-, race-, age-, and risk-factor-specific hepatitis
      C prevalence and mortality rates. Nine strategies combined screening (no
      screening, risk-factor guided screening, or birth-cohort screening) and treatment
      (standard therapy-peginterferon alfa and ribavirin, Interleukin-28B-guided
      (IL28B) triple-therapy-standard therapy plus a protease inhibitor, or universal
      triple therapy). Response-guided treatment depended on HCV genotype. Outcomes
      include discounted lifetime costs (2010 dollars) and quality adjusted life-years
      (QALYs). Compared to no screening, risk-factor guided and birth-cohort screening
      for 50 year-olds gained 0.7 to 3.5 quality adjusted life-days and cost $168 to
      $568 per person. Birth-cohort screening provided more benefit per dollar than
      risk-factor guided screening and cost $65,749 per QALY if followed by universal
      triple therapy compared to screening followed by IL28B-guided triple therapy. If
      only 10% of screen-detected, eligible patients initiate treatment at each
      opportunity, birth-cohort screening with universal triple therapy costs $241,100
      per QALY. Assuming treatment with triple therapy, screening all individuals aged
      40-64 years costs less than $100,000 per QALY. CONCLUSIONS: The cost
      effectiveness of one-time birth-cohort hepatitis C screening for 40-64 year olds
      is comparable to other screening programs, provided that the healthcare system
      has sufficient capacity to deliver prompt treatment and appropriate follow-on
      care to many newly screen-detected individuals.

PMID- 23533596
TI  - Overexpression of CD151 predicts prognosis in patients with resected gastric
      cancer.
AB  - PURPOSE: The tetraspanin CD151 acts as a promoter of metastasis and invasion in
      several tumors. However, the role of CD151 in human gastric cancer (HGC) remains
      unclear. METHODS: Twenty HGC specimens and matched nontumor samples, human
      gastric epithelial cells (HGEC), and four gastric cancer cell lines were used to
      analyze CD151 expression. Short hairpin RNA-mediated downregulation of CD151
      expression in HGC cells was performed to examine the role of CD151 in the
      proliferation and metastasis/invasion of HGC cells in vivo and in vitro. The
      relationship of CD151 with integrin alpha3 in HGC cells was investigated by
      silencing integrin alpha3 followed by co-immunoprecipitation and
      immunofluorescence staining. Finally, the prognostic value of CD151 and integrin
      alpha3 was evaluated by immunohistochemistry in tissue microarrays of 76 HGC
      patients. RESULTS: CD151 was expressed at higher levels in HGC tissues and HGC
      cells than in nontumor tissues and HGEC cells. Down-regulation of CD151 by vshRNA
      CD151 impaired metastasis and invasion of HGC-27 cells, but did not affect cell
      proliferation. CD151 formed a complex with integrin alpha3 in HGC cells. CD151
      cDNA transfection rescued the metastatic potential and invasiveness of HGC-27
      vshCD151 cells, but not those of HGC-27-vshintegrin alpha3 cells in vitro.
      Clinically, CD151 overexpression was significantly correlated with high TNM
      stage, depth of invasion and positive lymph node involvement (p<0.05), and high
      levels of integrin alpha3 were associated with large tumor size, high TNM stage,
      depth of invasion and lymph node involvement (p<0.05). Importantly, the
      postoperative 5-year overall survival of patients with CD151(low) and/or integrin
      alpha3(low) was higher than that of patients with CD151(high) and/or integrin
      alpha3(high). CONCLUSION: CD151 is positively associated with the invasiveness of
      HGC, and CD151 or the combination of CD151 and integrin alpha3 is a novel marker
      for predicting the prognosis of HGC patients and may be potential therapeutic
      targets.

PMID- 23533597
TI  - Evaluating purifying selection in the mitochondrial DNA of various mammalian
      species.
AB  - Mitochondrial DNA (mtDNA), the circular DNA molecule inside the mitochondria of
      all eukaryotic cells, has been shown to be under the effect of purifying
      selection in several species. Traditional testing of purifying selection has been
      based simply on ratios of nonsynonymous to synonymous mutations, without
      considering the relative age of each mutation, which can be determined by
      phylogenetic analysis of this non-recombining molecule. The incorporation of a
      mutation time-ordering from phylogeny and of predicted pathogenicity scores for
      nonsynonymous mutations allow a quantitative evaluation of the effects of
      purifying selection in human mtDNA. Here, by using this additional information,
      we show that purifying selection undoubtedly acts upon the mtDNA of other
      mammalian species/genera, namely Bos sp., Canis lupus, Mus musculus, Orcinus
      orca, Pan sp. and Sus scrofa. The effects of purifying selection were comparable
      in all species, leading to a significant major proportion of nonsynonymous
      variants with higher pathogenicity scores in the younger branches of the tree. We
      also derive recalibrated mutation rates for age estimates of ancestors of these
      various species and proposed a correction curve in order to take into account the
      effects of selection. Understanding this selection is fundamental to evolutionary
      studies and to the identification of deleterious mutations.

PMID- 23533598
TI  - Block and boost DNA transfer: opposite roles of OmpA in natural and artificial
      transformation of Escherichia coli.
AB  - Our previous work established that DNA is naturally transferable on agar plates
      through a new transformation system which is regulated by the stationary phase
      master regulator RpoS in Escherichia coli. In this transformation system, neither
      additional Ca(2+) nor heat shock is required. Instead, transformation is
      stimulated by agar. The membrane protein OmpA, a gated pore permeable to ions and
      larger solutes, serves as a receptor for DNA transfer during bacteriophage
      infection and conjugation. However, it remains unknown how DNA transfers across
      membranes and whether OmpA is involved in transformation of E. coli. Here, we
      explored potential roles of OmpA in natural and chemical transformation of E.
      coli. We observed that ompA inactivation significantly improved natural
      transformation on agar plates, indicating that OmpA blocks DNA transfer.
      Transformation promotion by ompA inactivation also occurred on soft plates,
      indicating that OmpA blocks DNA transfer independent of agar. By contrast,
      compared with the wild-type strain, chemical transformation of the ompA mutant
      was lower, indicating that OmpA has a role in DNA transfer. Inactivation of ompA
      also reduced chemical transformation in solution containing less Ca(2+) or with a
      shortened time for heat shock, suggesting that the promotion effect of OmpA on
      DNA transfer does not solely rely on Ca(2+) or heat shock. We conclude that OmpA
      plays opposite roles in natural and chemical transformation: it blocks DNA uptake
      on agar plates but promotes DNA transfer in the liquid Ca(2+) solution.
      Considering that no single factor was identified to reverse the function of OmpA,
      we propose that multiple factors may cooperate in the functional reversal of OmpA
      during natural and artificial transformation of E. coli. Finally, we observed
      that ompA transcription was not affected by the expression of RpoS, excluding the
      possibility that RpoS regulates DNA transfer by suppressing ompA transcription.

PMID- 23533599
TI  - The nexus between VEGF and NFkappaB orchestrates a hypoxia-independent
      neovasculogenesis.
AB  - Nuclear Factor-Kappa B [NFkappaB] activation triggers the elevation of various
      pro-angiogenic factors that contribute to the development and progression of
      diabetic vasculopathies. It has been demonstrated that vascular endothelial
      growth factor [VEGF] activates NFkappaB signaling pathway. Under the ischemic
      microenvironments, hypoxia-inducible factor-1 [HIF-1] upregulates the expression
      of several proangiogenic mediators, which play crucial roles in ocular
      pathologies. Whereas YC-1, a soluble guanylyl cyclase [sGC] agonist, inhibits HIF
      1 and NFkappaB signaling pathways in various cell and animal models. Throughout
      this investigation, we examined the molecular link between VEGF and NFkappaB
      under a hypoxia-independent microenvironment in human retinal microvascular
      endothelial cells [hRMVECs]. Our data indicate that VEGF promoted retinal
      neovasculogenesis via NFkappaB activation, enhancement of its DNA-binding
      activity, and upregulating NFkappaB/p65, SDF-1, CXCR4, FAK, alphaVbeta3,
      alpha5beta1, EPO, ET-1, and MMP-9 expression. Conversely, YC-1 impaired the
      activation of NFkappaB and its downstream signaling pathways, via attenuating
      IkappaB kinase phosphorylation, degradation and activation, and thus suppressing
      p65 phosphorylation, nuclear translocation, and inhibiting NFkappaB-DNA binding
      activity. We report for the first time that the nexus between VEGF and NFkappaB
      is implicated in coordinating a scheme that upregulates several pro-angiogenic
      molecules, which promotes retinal neovasculogenesis. Our data may suggest the
      potential use of YC-1 to attenuate the deleterious effects that are associated
      with hypoxia/ischemia-independent retinal vasculopathies.

PMID- 23533600
TI  - CNV analysis in Tourette syndrome implicates large genomic rearrangements in
      COL8A1 and NRXN1.
AB  - Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic
      component. However, the genetic architecture of TS remains uncertain. Copy number
      variation (CNV) has been shown to contribute to the genetic make-up of several
      neurodevelopmental conditions, including schizophrenia and autism. Here we
      describe CNV calls using SNP chip genotype data from an initial sample of 210 TS
      cases and 285 controls ascertained in two Latin American populations. After
      extensive quality control, we found that cases (N = 179) have a significant
      excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234).
      Amongst 24 large CNVs seen only in the cases, we observed four duplications of
      the COL8A1 gene region. We also found two cases with ~400 kb deletions involving
      NRXN1, a gene previously implicated in neurodevelopmental disorders, including
      TS. Follow-up using multiplex ligation-dependent probe amplification (and
      including 53 more TS cases) validated the CNV calls and identified additional
      patients with rearrangements in COL8A1 and NRXN1, but none in controls.
      Examination of available parents indicates that two out of three NRXN1 deletions
      detected in the TS cases are de-novo mutations. Our results are consistent with
      the proposal that rare CNVs play a role in TS aetiology and suggest a possible
      role for rearrangements in the COL8A1 and NRXN1 gene regions.

PMID- 23533601
TI  - Uric acid as a risk factor for cardiovascular disease and mortality in
      overweight/obese individuals.
AB  - BACKGROUND: The predictive value of serum uric acid (SUA) for adverse
      cardiovascular events among obese and overweight patients is not known, but
      potentially important because of the relation between hyperuricaemia and obesity.
      METHODS: The relationship between SUA and risk of cardiovascular adverse outcomes
      (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or
      cardiovascular death) and all-cause mortality, respectively, was evaluated in a
      post-hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.
      Participants enrolled in SCOUT were obese or overweight with pre-existing
      diabetes and/or cardiovascular disease (CVD). Cox models were used to assess the
      role of SUA as an independent risk factor. RESULTS: 9742 subjects were included
      in the study; 83.6% had diabetes, and 75.1% had CVD. During an average follow-up
      time of 4.2 years, 1043 subjects had a primary outcome (myocardial infarction,
      resuscitated cardiac arrest, stroke, or cardiovascular death), and 816 died. In a
      univariate Cox model, the highest SUA quartile was associated with an increased
      risk of cardiovascular adverse outcomes compared with the lowest SUA quartile in
      women (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.20-2.10). In
      multivariate analyses, adjusting for known cardiovascular risk factors the
      increased risk for the highest SUA quartile was no longer statistically
      significant among women (HR: 0.99; 95% CI: 0.72-1.36) nor was it among men.
      Analyses of all-cause mortality found an interaction between sex and SUA. In a
      multivariate Cox model including women only, the highest SUA quartile was
      associated with an increased risk in all-cause mortality compared to the lowest
      SUA quartile (HR: 1.51; 95% CI: 1.08-2.12). No relationship was observed in men
      (HR: 1.06; 95% CI: 0.82-1.36). CONCLUSION: SUA was not an independent predictor
      of cardiovascular disease and death in these high-risk overweight/obese people.
      However, our results suggested that SUA was an independent predictor of all-cause
      mortality in women.

PMID- 23533602
TI  - Association of PER2 genotype and stressful life events with alcohol drinking in
      young adults.
AB  - BACKGROUND: Clock genes govern circadian rhythms and shape the effect of alcohol
      use on the physiological system. Exposure to severe negative life events is
      related to both heavy drinking and disturbed circadian rhythmicity. The aim of
      this study was 1) to extend previous findings suggesting an association of a
      haplotype tagging single nucleotide polymorphism of PER2 gene with drinking
      patterns, and 2) to examine a possible role for an interaction of this gene with
      life stress in hazardous drinking. METHODS: Data were collected as part of an
      epidemiological cohort study on the outcome of early risk factors followed since
      birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped
      for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back
      interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress
      was assessed as the number of severe negative life events during the past four
      years reported in a questionnaire and validated by interview. RESULTS:
      Individuals with the minor G allele of rs56013859 were found to be less engaged
      in alcohol use, drinking at only 72% of the days compared to homozygotes for the
      major A allele. Moreover, among regular drinkers, a gene x environment
      interaction emerged (p = .020). While no effects of genotype appeared under
      conditions of low stress, carriers of the G allele exhibited less hazardous
      drinking than those homozygous for the A allele when exposed to high stress.
      CONCLUSIONS: These findings may suggest a role of the circadian rhythm gene PER2
      in both the drinking patterns of young adults and in moderating the impact of
      severe life stress on hazardous drinking in experienced alcohol users. However,
      in light of the likely burden of multiple tests, the nature of the measures used
      and the nominal evidence of interaction, replication is needed before drawing
      firm conclusions.

PMID- 23533603
TI  - Prognostic value of cancer stem cell marker CD133 expression in gastric cancer: a
      systematic review.
AB  - OBJECTIVE: To investigate the correlation between CD133-positive gastric cancer
      and clinicopathological features and its impact on survival. METHODS: A search in
      the Medline and Chinese CNKI (up to 1 Dec 2011) was performed using the following
      keywords gastric cancer, CD133, AC133, prominin-1 etc. Electronic searches were
      supplemented by hand searching reference lists, abstracts and proceedings from
      meetings. Outcomes included overall survival and various clinicopathological
      features. RESULTS: A total of 773 gastric cancer patients from 7 studies were
      included. The median rate of CD133 expression by immunohistochemistry (IHC) was
      44.8% (15.2%-57.4%) from 5 studies, and that by reverse transcription polymerase
      chain reaction (RT-PCR) was 91.3% (66.7%-100%) from 4 studies. The accumulative 5
      year overall survival rates of CD133-positive and CD133-negative patients were
      21.4% and 55.7%, respectively. Meta-analysis showed that CD133-positive patients
      had a significant worse 5-year overall survival compared to the negative ones (OR
      = 0.20, 95% CI 0.14-0.29, P<0.00001). With respect to clinicopathological
      features, CD133 overexpression by IHC method was closely correlated with tumor
      size, N stage, lymphatic/vascular infiltration, as well as TNM stage. CONCLUSION:
      CD133-positive gastric cancer patients had worse prognosis, and was associated
      with common clinicopathological poor prognostic factors.

PMID- 23533604
TI  - Meconium fatty acid ethyl esters as biomarkers of late gestational ethanol
      exposure and indicator of ethanol-induced multi-organ injury in fetal sheep.
AB  - BACKGROUND: Meconium fatty acid ethyl esters (FAEE) constitute a biomarker of
      heavy fetal ethanol exposure. Our objective was to measure meconium FAEE in fetal
      sheep following daily, relatively moderate-dose ethanol exposure in late
      gestation, and to evaluate their utility in identifying fetal organ-system
      injury. METHODS: Pregnant ewes received ethanol (0.75 g/kg; n = 14) or saline (n
      = 8) via 1-h i.v. infusion daily during the third trimester equivalent, while
      additional pregnant sheep served as untreated controls (n = 6). The daily ethanol
      regimen produced similar maximal maternal and fetal plasma ethanol concentrations
      of 0.11-0.12 g/dL. Ewes and fetuses were euthanized shortly before term, and
      meconium was collected and analyzed for FAEE (ethyl palmitate, stearate,
      linoleate, and oleate). RESULTS: Meconium total FAEE concentration was
      significantly higher in ethanol-exposed fetuses compared with controls, and a
      positive cut-off of 0.0285 nmol total FAEE/g meconium had 93.3% sensitivity and
      specificity for detecting fetal ethanol exposure. When the studied animals
      (ethanol-exposed and controls) were classified according to meconium FAEE
      concentration, FAEE-positive and FAEE-negative groups frequently differed with
      respect to previously examined pathological endpoints, including nephron
      endowment, lung collagen deposition, cardiomyocyte maturation, and tropoelastin
      gene expression in cerebral vessels. Furthermore, in all studied animals as a
      group (ethanol-exposed and controls combined), meconium FAEE concentration was
      correlated with many of these pathological endpoints in fetal organs.
      CONCLUSIONS: We conclude that, in fetal sheep, meconium FAEE could serve as a
      biomarker of daily ethanol exposure in late gestation and could identify fetuses
      with subtle ethanol-induced toxic effects in various organs. This study
      illustrates the potential for using meconium FAEE to identify neonates at risk
      for dysfunction of major organs following in-utero ethanol exposure that does not
      result in overt physical signs of ethanol teratogenicity.

PMID- 23533605
TI  - Compression of FASTQ and SAM format sequencing data.
AB  - Storage and transmission of the data produced by modern DNA sequencing
      instruments has become a major concern, which prompted the Pistoia Alliance to
      pose the SequenceSqueeze contest for compression of FASTQ files. We present
      several compression entries from the competition, Fastqz and Samcomp/Fqzcomp,
      including the winning entry. These are compared against existing algorithms for
      both reference based compression (CRAM, Goby) and non-reference based compression
      (DSRC, BAM) and other recently published competition entries (Quip, SCALCE). The
      tools are shown to be the new Pareto frontier for FASTQ compression, offering
      state of the art ratios at affordable CPU costs. All programs are freely
      available on SourceForge. Fastqz: https://sourceforge.net/projects/fastqz/,
      fqzcomp: https://sourceforge.net/projects/fqzcomp/, and samcomp:
      https://sourceforge.net/projects/samcomp/.

PMID- 23533606
TI  - Risk factors for development of hemolytic uremic syndrome in a cohort of adult
      patients with STEC 0104:H4 infection.
AB  - The outbreak of Shiga toxin producing E.coli O104:H4 in northern Germany in 2011
      was one of the largest worldwide and involved mainly adults. Post-diarrheal
      hemolytic uremic syndrome (HUS) occurred in 22% of STEC positive patients. This
      study's aim was to assess risk factors for HUS in STEC-infected patients and to
      develop a score from routine hospital parameters to estimate patient risks for
      developing HUS. In a cohort analysis, adult patients with STEC infection were
      included in five participating hospitals in northern Germany between May and July
      2011. Clinical data were obtained from questionnaires and medical records,
      laboratory data were extracted from hospitals' electronic data systems. HUS was
      defined as thrombocytopenia, hemolytic anemia and acute renal dysfunction. Random
      forests and multivariate logistic regression were used to identify risk factors
      for HUS and develop a score using the estimated coefficients as weights. Among
      259 adults with STEC infection, vomiting (OR 3.48,95%CI 1.88-6.53), visible blood
      in stools (OR 3.91,95%CI1.20-16.01), age above 75 years (OR 3.27, 95%CI 1.12
      9.70) and elevated leukocyte counts (OR 1.20, 95%CI 1.10-1.31, per 1000
      cells/mm(3)) were identified as independent risk factors for HUS. A score using
      these variables has an area under the ROC curve of 0.74 (95%CI 0.68-0.80).
      Vomiting, visible blood in stools, higher leukocyte counts, and higher age
      indicate increased risk for developing HUS. A score using these variables might
      help to identify high risk patients who potentially benefit from aggressive pre
      emptive treatment to prevent or mitigate the devastating consequences of HUS.

PMID- 23533607
TI  - Phylogenetic analysis reveals a cryptic species Blastomyces gilchristii, sp. nov.
      within the human pathogenic fungus Blastomyces dermatitidis.
AB  - BACKGROUND: Analysis of the population genetic structure of microbial species is
      of fundamental importance to many scientific disciplines because it can identify
      cryptic species, reveal reproductive mode, and elucidate processes that
      contribute to pathogen evolution. Here, we examined the population genetic
      structure and geographic differentiation of the sexual, dimorphic fungus
      Blastomyces dermatitidis, the causative agent of blastomycosis.
      METHODOLOGY/PRINCIPAL FINDINGS: Criteria for Genealogical Concordance
      Phylogenetic Species Recognition (GCPSR) applied to seven nuclear loci (arf6,
      chs2, drk1, fads, pyrF, tub1, and its-2) from 78 clinical and environmental
      isolates identified two previously unrecognized phylogenetic species. Four of
      seven single gene phylogenies examined (chs2, drk1, pyrF, and its-2) supported
      the separation of Phylogenetic Species 1 (PS1) and Phylogenetic Species 2 (PS2)
      which were also well differentiated in the concatenated chs2-drk1-fads-pyrF-tub1
      arf6-its2 genealogy with all isolates falling into one of two evolutionarily
      independent lineages. Phylogenetic species were genetically distinct with
      interspecific divergence 4-fold greater than intraspecific divergence and a high
      Fst value (0.772, P<0.001) indicative of restricted gene flow between PS1 and
      PS2. Whereas panmixia expected of a single freely recombining population was not
      observed, recombination was detected when PS1 and PS2 were assessed separately,
      suggesting reproductive isolation. Random mating among PS1 isolates, which were
      distributed across North America, was only detected after partitioning isolates
      into six geographic regions. The PS2 population, found predominantly in the hyper
      endemic regions of northwestern Ontario, Wisconsin, and Minnesota, contained a
      substantial clonal component with random mating detected only among unique
      genotypes in the population. CONCLUSIONS/SIGNIFICANCE: These analyses provide
      evidence for a genetically divergent clade within Blastomyces dermatitidis, which
      we use to describe a novel species, Blastomyces gilchristii sp. nov. In addition,
      we discuss the value of population genetic and phylogenetic analyses as a
      foundation for disease surveillance, understanding pathogen evolution, and
      discerning phenotypic differences between phylogenetic species.

PMID- 23533608
TI  - Derivation and expansion using only small molecules of human neural progenitors
      for neurodegenerative disease modeling.
AB  - Phenotypic drug discovery requires billions of cells for high-throughput
      screening (HTS) campaigns. Because up to several million different small
      molecules will be tested in a single HTS campaign, even small variability within
      the cell populations for screening could easily invalidate an entire campaign.
      Neurodegenerative assays are particularly challenging because neurons are post
      mitotic and cannot be expanded for implementation in HTS. Therefore, HTS for
      neuroprotective compounds requires a cell type that is robustly expandable and
      able to differentiate into all of the neuronal subtypes involved in disease
      pathogenesis. Here, we report the derivation and propagation using only small
      molecules of human neural progenitor cells (small molecule neural precursor
      cells; smNPCs). smNPCs are robust, exhibit immortal expansion, and do not require
      cumbersome manual culture and selection steps. We demonstrate that smNPCs have
      the potential to clonally and efficiently differentiate into neural tube
      lineages, including motor neurons (MNs) and midbrain dopaminergic neurons (mDANs)
      as well as neural crest lineages, including peripheral neurons and mesenchymal
      cells. These properties are so far only matched by pluripotent stem cells.
      Finally, to demonstrate the usefulness of smNPCs we show that mDANs
      differentiated from smNPCs with LRRK2 G2019S are more susceptible to apoptosis in
      the presence of oxidative stress compared to wild-type. Therefore, smNPCs are a
      powerful biological tool with properties that are optimal for large-scale disease
      modeling, phenotypic screening, and studies of early human development.

PMID- 23533609
TI  - A minimal anaphase promoting complex/cyclosome (APC/C) in Trypanosoma brucei.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin
      ligase that initiates chromosome segregation and mitotic exit by targeting
      critical cell-cycle regulators for proteolytic destruction. Previously, seven
      APC/C subunit homologues were identified in the genome of Trypanosoma brucei. In
      the present study, we tested five of them in yeast complementation studies and
      found none of them capable of complementing the yeast mutants lacking the
      corresponding subunits, suggesting significant discrepancies between the two
      APC/C's. Subunit homologues of mitotic checkpoint complex (MCC) have not yet been
      identified in T. brucei, raising the possibility that a MCC-APC/C complex
      equivalent may not exist in T. brucei. We performed tandem affinity purification
      of the protein complex containing a APC1 fusion protein expressed in the cells
      enriched in different phases of the cell cycle of procyclic form T. brucei, and
      compared their protein profiles using LC-MS/MS analyses. The seven putative APC/C
      subunits were identified in the protein complex throughout the cell cycle
      together with three additional proteins designated the associated proteins (AP)
      AP1, AP2 and AP3. Abundance of the 10 proteins remained relatively unchanged
      throughout the cell cycle, suggesting that they are the core subunits of APC/C.
      AP1 turned out to be a homologue of APC4. An RNAi knockdown of APC4 and AP3
      showed no detectable cellular phenotype, whereas an AP2 knockdown enriched the
      cells in G2/M phase. The AP2-depleted cells showed stabilized mitotic cyclin B.
      An accumulation of poly-ubiquitinated cyclin B was indicated in the cells treated
      with the proteasome inhibitor MG132, demonstrating the involvement of proteasome
      in degrading poly-ubiquitinated cyclin B. In all, a 10-subunit APC/C machinery
      with a conserved function is identified in T. brucei without linking to a MCC
      like complex, thus indicating a unique T. brucei APC/C.

PMID- 23533610
TI  - Characterization of an ancient lepidopteran lateral gene transfer.
AB  - Bacteria to eukaryote lateral gene transfers (LGT) are an important potential
      source of material for the evolution of novel genetic traits. The explosion in
      the number of newly sequenced genomes provides opportunities to identify and
      characterize examples of these lateral gene transfer events, and to assess their
      role in the evolution of new genes. In this paper, we describe an ancient
      lepidopteran LGT of a glycosyl hydrolase family 31 gene (GH31) from an
      Enterococcus bacteria. PCR amplification between the LGT and a flanking insect
      gene confirmed that the GH31 was integrated into the Bombyx mori genome and was
      not a result of an assembly error. Database searches in combination with
      degenerate PCR on a panel of 7 lepidopteran families confirmed that the GH31 LGT
      event occurred deep within the Order approximately 65-145 million years ago. The
      most basal species in which the LGT was found is Plutella xylostella
      (superfamily: Yponomeutoidea). Array data from Bombyx mori shows that GH31 is
      expressed, and low dN/dS ratios indicates the LGT coding sequence is under strong
      stabilizing selection. These findings provide further support for the proposition
      that bacterial LGTs are relatively common in insects and likely to be an
      underappreciated source of adaptive genetic material.

PMID- 23533611
TI  - Assessing phospholipase A2 activity toward cardiolipin by mass spectrometry.
AB  - Cardiolipin, a major component of mitochondria, is critical for mitochondrial
      functioning including the regulation of cytochrome c release during apoptosis and
      proper electron transport. Mitochondrial cardiolipin with its unique bulky
      amphipathic structure is a potential substrate for phospholipase A2 (PLA2) in
      vivo. We have developed mass spectrometric methodology for analyzing PLA2
      activity toward various cardiolipin forms and demonstrate that cardiolipin is a
      substrate for sPLA2, cPLA2 and iPLA2, but not for Lp-PLA2. Our results also show
      that none of these PLA2s have significant PLA1 activities toward dilyso
      cardiolipin. To understand the mechanism of cardiolipin hydrolysis by PLA2, we
      also quantified the release of monolyso-cardiolipin and dilyso-cardiolipin in the
      PLA2 assays. The sPLA2s caused an accumulation of dilyso-cardiolipin, in contrast
      to iPLA2 which caused an accumulation of monolyso-cardiolipin. Moreover,
      cardiolipin inhibits iPLA2 and cPLA2, and activates sPLA2 at low mol fractions in
      mixed micelles of Triton X-100 with the substrate 1-palmitoyl-2-arachidonyl-sn
      phosphtidylcholine. Thus, cardiolipin functions as both a substrate and a
      regulator of PLA2 activity and the ability to assay the various forms of PLA2 is
      important in understanding its function.

PMID- 23533612
TI  - Step detection in single-molecule real time trajectories embedded in correlated
      noise.
AB  - Single-molecule real time trajectories are embedded in high noise. To extract
      kinetic or dynamic information of the molecules from these trajectories often
      requires idealization of the data in steps and dwells. One major premise behind
      the existing single-molecule data analysis algorithms is the gaussian 'white'
      noise, which displays no correlation in time and whose amplitude is independent
      on data sampling frequency. This so-called 'white' noise is widely assumed but
      its validity has not been critically evaluated. We show that correlated noise
      exists in single-molecule real time trajectories collected from optical tweezers.
      The assumption of white noise during analysis of these data can lead to serious
      over- or underestimation of the number of steps depending on the algorithms
      employed. We present a statistical method that quantitatively evaluates the
      structure of the underlying noise, takes the noise structure into account, and
      identifies steps and dwells in a single-molecule trajectory. Unlike existing data
      analysis algorithms, this method uses Generalized Least Squares (GLS) to detect
      steps and dwells. Under the GLS framework, the optimal number of steps is chosen
      using model selection criteria such as Bayesian Information Criterion (BIC).
      Comparison with existing step detection algorithms showed that this GLS method
      can detect step locations with highest accuracy in the presence of correlated
      noise. Because this method is automated, and directly works with high bandwidth
      data without pre-filtering or assumption of gaussian noise, it may be broadly
      useful for analysis of single-molecule real time trajectories.

PMID- 23533613
TI  - Investigation of radiation-induced transcriptome profile of radioresistant non
      small cell lung cancer A549 cells using RNA-seq.
AB  - Radioresistance is a main impediment to effective radiotherapy for non-small cell
      lung cancer (NSCLC). Despite several experimental and clinical studies of
      resistance to radiation, the precise mechanism of radioresistance in NSCLC cells
      and tissues still remains unclear. This result could be explained by limitation
      of previous researches such as a partial understanding of the cellular
      radioresistance mechanism at a single molecule level. In this study, we aimed to
      investigate extensive radiation responses in radioresistant NSCLC cells and to
      identify radioresistance-associating factors. For the first time, using RNA-seq,
      a massive sequencing-based approach, we examined whole-transcriptome alteration
      in radioresistant NSCLC A549 cells under irradiation, and verified significant
      radiation-altered genes and their chromosome distribution patterns. Also,
      bioinformatic approaches (GO analysis and IPA) were performed to characterize the
      radiation responses in radioresistant A549 cells. We found that epithelial
      mesenchymal transition (EMT), migration and inflammatory processes could be
      meaningfully related to regulation of radiation responses in radioresistant A549
      cells. Based on the results of bioinformatic analysis for the radiation-induced
      transcriptome alteration, we selected seven significant radiation-altered genes
      (SESN2, FN1, TRAF4, CDKN1A, COX-2, DDB2 and FDXR) and then compared radiation
      effects in two types of NSCLC cells with different radiosensitivity
      (radioresistant A549 cells and radiosensitive NCI-H460 cells). Interestingly,
      under irradiation, COX-2 showed the most significant difference in mRNA and
      protein expression between A549 and NCI-H460 cells. IR-induced increase of COX-2
      expression was appeared only in radioresistant A549 cells. Collectively, we
      suggest that COX-2 (also known as prostaglandin-endoperoxide synthase 2 (PTGS2))
      could have possibility as a putative biomarker for radioresistance in NSCLC
      cells.

PMID- 23533614
TI  - Genetic diversity in introduced golden mussel populations corresponds to vector
      activity.
AB  - We explored possible links between vector activity and genetic diversity in
      introduced populations of Limnoperna fortunei by characterizing the genetic
      structure in native and introduced ranges in Asia and South America. We surveyed
      24 populations: ten in Asia and 14 in South America using the mitochondrial
      cytochrome c oxidase subunit I (COI) gene, as well as eight polymorphic
      microsatellite markers. We performed population genetics and phylogenetic
      analyses to investigate population genetic structure across native and introduced
      regions. Introduced populations in Asia exhibit higher genetic diversity (H(E) =
      0.667-0.746) than those in South America (H(E) =  0.519-0.575), suggesting higher
      introduction effort for the former populations. We observed pronounced
      geographical structuring in introduced regions, as indicated by both
      mitochondrial and nuclear markers based on multiple genetic analyses including
      pairwise F(ST), F(ST), bayesian clustering method, and three-dimensional
      factorial correspondence analyses. Pairwise F(ST) values within both Asia (F(ST)
      = 0.017-0.126, P = 0.000-0.009) and South America (F(ST) =0.004-0.107, P = 0.000
      0.721) were lower than those between continents (F(ST) = 0.180-0.319, P = 0.000).
      Fine-scale genetic structuring was also apparent among introduced populations in
      both Asia and South America, suggesting either multiple introductions of distinct
      propagules or strong post-introduction selection and demographic stochasticity.
      Higher genetic diversity in Asia as compared to South America is likely due to
      more frequent propagule transfers associated with higher shipping activities
      between source and donor regions within Asia. This study suggests that the
      intensity of human-mediated introduction vectors influences patterns of genetic
      diversity in non-indigenous species.

PMID- 23533615
TI  - Abstract spatial reasoning as an autistic strength.
AB  - Autistic individuals typically excel on spatial tests that measure abstract
      reasoning, such as the Block Design subtest on intelligence test batteries and
      the Raven's Progressive Matrices nonverbal test of intelligence. Such well
      replicated findings suggest that abstract spatial processing is a relative and
      perhaps absolute strength of autistic individuals. However, previous studies have
      not systematically varied reasoning level--concrete vs. abstract--and test domain
      -spatial vs. numerical vs. verbal, which the current study did. Autistic
      participants (N = 72) and non-autistic participants (N = 72) completed a battery
      of 12 tests that varied by reasoning level (concrete vs. abstract) and domain
      (spatial vs. numerical vs. verbal). Autistic participants outperformed non
      autistic participants on abstract spatial tests. Non-autistic participants did
      not outperform autistic participants on any of the three domains (spatial,
      numerical, and verbal) or at either of the two reasoning levels (concrete and
      abstract), suggesting similarity in abilities between autistic and non-autistic
      individuals, with abstract spatial reasoning as an autistic strength.

PMID- 23533616
TI  - Endoplasmic reticulum stress signaling is involved in mitomycin C (MMC)-induced
      apoptosis in human fibroblasts via PERK pathway.
AB  - Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in
      various cell types, including fibroblasts. Previous studies have shown that
      mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC
      on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC
      induced apoptosis in human primary fibroblasts was investigated by exposing cells
      to a single dose of MMC for 5 minutes. Significant inhibition of cell
      proliferation and increased apoptosis were observed using a cell viability assay,
      Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL
      (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining.
      Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP
      ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis
      was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and
      C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded
      protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating
      transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream
      signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced
      apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression,
      suggesting that ER stress is involved in MMC-induced fibroblast apoptosis.
      Interestingly, knockdown of PERK significantly decreased ER stress-mediated
      apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive
      oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho
      PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is
      triggered by ROS generation and PERK activation.

PMID- 23533617
TI  - Dual role of G-runs and hnRNP F in the regulation of a mutation-activated
      pseudoexon in the fibrinogen gamma-chain transcript.
AB  - Most pathological pseudoexon inclusion events originate from single activating
      mutations, suggesting that many intronic sequences are on the verge of becoming
      exons. However, the precise mechanisms controlling pseudoexon definition are
      still largely unexplored. Here, we investigated the cis-acting elements and trans
      acting regulatory factors contributing to the regulation of a previously
      described fibrinogen gamma-chain (FGG) pseudoexon, which is activated by a deep
      intronic mutation (IVS6-320A>T). This pseudoexon contains several G-run elements,
      which may be bound by heterogeneous nuclear ribonucleoproteins (hnRNPs) F and H.
      To explore the effect of these proteins on FGG pseudoexon inclusion, both
      silencing and overexpression experiments were performed in eukaryotic cells.
      While hnRNP H did not significantly affect pseudoexon splicing, hnRNP F promoted
      pseudoexon inclusion, indicating that these two proteins have only partially
      redundant functions. To verify the binding of hnRNP F and the possible
      involvement of other trans-acting splicing modulators, pulldown experiments were
      performed on the region of the pseudoexon characterized by both a G-run and
      enrichment for exonic splicing enhancers. This 25-bp-long region strongly binds
      hnRNP F/H and weakly interacts with Serine/Arginine-rich protein 40, which
      however was demonstrated to be dispensable for FGG pseudoexon inclusion in
      overexpression experiments. Deletion analysis, besides confirming the splicing
      promoting role of the G-run within this 25-bp region, demonstrated that two
      additional hnRNP F binding sites might instead function as silencer elements.
      Taken together, our results indicate a major role of hnRNP F in regulating FGG
      pseudoexon inclusion, and strengthen the notion that G-runs may function either
      as splicing enhancers or silencers of the same exon.

PMID- 23533618
TI  - Trends in antiretroviral therapy and prevalence of HIV drug resistance mutations
      in Sweden 1997-2011.
AB  - OBJECTIVE: Describe trends in antiretroviral treatments and drug resistance
      mutations among Swedish HIV-patients over time 1997-2011. METHODS: Treatment
      histories, viral sequences, and demographic and clinical data were retrieved from
      the national database InfCareHIV. All ART-experienced patients were included (N =
      6537), while resistance tests were restricted to those obtained >=90 days after
      ART start. This cohort is fully representative for Sweden since the database
      covers virtually all diagnosed HIV-patients since the start of the epidemic.
      Patients were grouped according to the year of first ART, and treatments and
      mutations were analyzed by calendar year. RESULTS: The prevalence of major drug
      resistance mutations decreased dramatically over time, most rapidly between 2003
      and 2007. Since then there has been a continued slow decrease for NRTI- and PI
      associated mutations with an overall prevalence among all ART-experienced
      patients at 1.1% (NRTI) and 0.3% (PI) in 2011. NNRTI resistance reached the
      lowest level in 2007-2009 (0.6%), but is now increasing (0.9% in 2011). Patients
      with first ART exposure before 2001 are still highly overrepresented among those
      with PI and, to a lesser extent, NRTI resistance. In contrast, almost half of the
      patients with NNRTI mutations in 2011 initiated their first ART after 2007.
      CONCLUSIONS: Tremendous improvements in ART options and knowledge have resulted
      in rapidly declining levels of resistance, and most of the current NRTI and PI
      mutations are found among patients with a history of suboptimal treatments.
      However, NNRTI resistance is increasing and is primarily found in patients
      infected in low- and middle-income countries who initiated ART in recent years.
      It is plausible that these patients were infected with resistant strains and it
      is therefore suggested that resource-rich countries like Sweden should test for
      resistance in minor quasispecies or use PI-based first-line regimens in patients
      who are at increased risk of carrying resistant virus.

PMID- 23533619
TI  - Effect of sugarcane burning or green harvest methods on the Brazilian Cerrado
      soil bacterial community structure.
AB  - BACKGROUND: The Brazilian Cerrado is one of the most important biodiversity
      reservoirs in the world. The sugarcane cultivation is expanding in this biome and
      necessitates the study of how it may impact the soil properties of the Cerrado.
      There is a lack of information especially about the impacts of different
      sugarcane management on the native bacterial communities of Cerrado soil.
      Therefore, our objective was to evaluate and compare the soil bacterial community
      structure of the Cerrado vegetation with two sugarcane systems. METHODS: We
      evaluated samples under native vegetation and the impact of the two most commonly
      used management strategies for sugarcane cultivation (burnt cane and green cane)
      on this diversity using pyrosequencing and quantitative PCR of the rrs gene (16S
      rRNA). RESULTS AND CONCLUSIONS: Nineteen different phyla were identified, with
      Acidobacteria (~35%), Proteobacteria (~24%) and Actinobacteria (~21%) being the
      most abundant. Many of the sequences were represented by few operational
      taxonomic units (OTUs, 3% of dissimilarity), which were found in all treatments.
      In contrast, there were very strong patterns of local selection, with many OTUs
      occurring only in one sample. Our results reveal a complex bacterial diversity,
      with a large fraction of microorganisms not yet described, reinforcing the
      importance of this biome. As possible sign of threat, the qPCR detected a
      reduction of the bacterial population in agricultural soils compared with native
      Cerrado soil communities. We conclude that sugarcane cultivation promoted
      significant structural changes in the soil bacterial community, with Firmicutes
      phylum and Acidobacteria classes being the groups most affected.

PMID- 23533620
TI  - The human CD8beta M-4 isoform dominant in effector memory T cells has distinct
      cytoplasmic motifs that confer unique properties.
AB  - The CD8 co-receptor influences T cell recognition and responses in both anti
      tumor and anti-viral immunity. During evolution in the ancestor of humans and
      chimpanzees, the CD8B gene acquired two additional exons. As a result, in humans,
      there are four CD8beta splice variants (M1 to M4) that differ in their
      cytoplasmic tails. The M-1 isoform which is the equivalent of murine CD8beta, is
      predominantly expressed in naive T cells, whereas, the M-4 isoform is
      predominantly expressed in effector memory T cells. The characteristics of the M
      4 isoform conferred by its unique 36 amino acid cytoplasmic tail are not known.
      In this study, we identified a dihydrophobic leucine-based receptor
      internalization motif in the cytoplasmic tail of M-4 that regulated its cell
      surface expression and downregulation after activation. Further the M-4
      cytoplasmic tail was able to associate with ubiquitinated targets in 293T cells
      and mutations in the amino acids NPW, a potential EH domain binding site, either
      enhanced or inhibited the interaction. In addition, the M-4 tail was itself mono
      ubiquitinated on a lysine residue in both 293T cells and a human T cell line.
      When peripheral blood human T cells expressed CD8alphabeta M-4, the frequency of
      MIP-1beta secreting cells responding to antigen presenting cells was two-fold
      higher as compared to CD8alphabeta M-1 expressing T cells. Thus, the cytoplasmic
      tail of the CD8beta M-4 isoform has unique characteristics, which likely
      contributed to its selective expression and function in human effector memory T
      cells.

PMID- 23533621
TI  - Regeneration of Betula albosinensis in strip clearcut and uncut forests of the
      Qinling Mountains in China.
AB  - To contribute to a better understanding of the regeneration strategy of Betula
      albosinensis forests and the likely reasons behind either the successful recovery
      or failure after strip clearcutting, we compared the population structures and
      spatial patterns of B. albosinensis in eight B. albosinensis stands in Qinling
      Mountains, China. Four cut and four uncut stands were selected, and each sampled
      using a single large plot (0.25 ha). Results indicated that, on the one hand, B.
      albosinensis recruitment was scarce (average of 48 stems ha(-1)) in the uncut
      stands, relative to the mature population (average of 259 stems ha(-1)),
      suggesting a failure of recruitment. On the other hand, the subsequent
      regeneration approximately 50 years after the strip clearcutting showed that the
      density of the target species seedlings and saplings has increased significantly,
      and the current average density of seedlings and saplings was 156 stems ha(-1).
      The clumped spatial pattern of B. albosinensis suggested that their regeneration
      was highly dependent on canopy disturbance. However, recruitment remained poor in
      the uncut stands because most gaps were small in scale. The successful
      regeneration of sunlight-loving B. albosinensis after strip clearcutting was
      attributed to the exposed land and availability of more sunlight. Bamboo density
      did not influence B. albosinensis recruitment in the uncut stands. However, stand
      regeneration was impeded after strip clearcutting; thus, removing bamboo is
      essential in improving the competitive status of B. albosinensis at the later
      stage of forest regeneration after clearcutting. The moderate severity of
      disturbance resulting from strip clearcutting reversed the degeneration trend of
      primary B. albosinensis stands. This outcome can help strike a balance between
      forest conservation and the demand for wood products by releasing space and
      exposing the forested land for recruitment. Life history traits and
      spatiotemporal disturbance magnitude are important factors to consider in
      implementing effective B. albosinensis regeneration strategies.

PMID- 23533622
TI  - A NF-kappaB-dependent dual promoter-enhancer initiates the lipopolysaccharide
      mediated transcriptional activation of the chicken lysozyme in macrophages.
AB  - The transcriptional activation of the chicken lysozyme gene (cLys) by
      lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS
      Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor
      (CTCF) from a negative regulatory element upstream of the lysozyme transcription
      start site. LINoCR is transcribed from a promoter originally characterized as a
      hormone response enhancer in the oviduct. Herein, we report the characterization
      of this cis-regulatory element (CRE). In activated macrophages, a 60 bp region
      bound by NF-kappaB, AP1 and C/EBPbeta controls this CRE, which is strictly
      dependent on NF-kappaB binding for its activity in luciferase assays. Moreover,
      the serine/threonine kinase IKKalpha, known to be recruited by NF-kappaB to NF
      kappaB-dependent genes is found at the CRE and within the transcribing regions of
      both cLys and LINoCR. Such repartition suggests a simultaneous promoter and
      enhancer activity of this CRE, initiating cLys transcriptional activation and
      driving CTCF eviction. This recruitment was transient despite persistence of both
      cLys transcription and NF-kappaB binding to the CRE. Finally, comparing cLys with
      other LPS-inducible genes indicates that IKKalpha detection within transcribing
      regions can be correlated with the presence of the elongating form of RNA
      polymerase II or concentrated in the 3' end of the gene.

PMID- 23533623
TI  - Targeted ablation of miR-21 decreases murine eosinophil progenitor cell growth.
AB  - MiR-21 is one of the most up-regulated miRNAs in multiple allergic diseases
      associated with eosinophilia and has been shown to positively correlate with
      eosinophil levels. Herein, we show that miR-21 is up-regulated during IL-5-driven
      eosinophil differentiation from progenitor cells in vitro. Targeted ablation of
      miR-21 leads to reduced eosinophil progenitor cell growth. Furthermore, miR-21(-/
      ) eosinophil progenitor cells have increased apoptosis as indicated by increased
      levels of annexin V positivity compared to miR-21(+/+) eosinophil progenitor
      cells. Indeed, miR-21(-/-) mice have reduced blood eosinophil levels in vivo and
      reduced eosinophil colony forming unit capacity in the bone marrow. Using gene
      expression microarray analysis, we identified dysregulation of genes involved in
      cell proliferation (e,g, Ms4a3, Grb7), cell cycle and immune response as the most
      significant pathways affected by miR-21 in eosinophil progenitors. These results
      demonstrate that miR-21 can regulate the development of eosinophils by
      influencing eosinophil progenitor cell growth. Our findings have identified one
      of the first miRNAs with a role in regulating eosinophil development.

PMID- 23533624
TI  - Circulation of different lineages of Dengue virus 2, genotype American/Asian in
      Brazil: dynamics and molecular and phylogenetic characterization.
AB  - The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into
      the Americas in the 80's. Although there is no data showing when this genotype
      was first introduced into Brazil, it was first detected in Brazil in 1990. After
      which the virus spread throughout the country and major epidemics occurred in
      1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained
      from serum samples of patients with dengue fever residing in Sao Jose do Rio
      Preto, Sao Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or
      envelope sequences were used to perform phylogenetic, phylogeographic and
      evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage
      (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were
      probably introduced there at least in 2007, prior to its detection in the 2008
      outbreak. DENV-2 circulation in Brazil is characterized by the introduction,
      displacement and circulation of three well-defined lineages in different times,
      most probably from the Caribbean. Thirty-seven unique amino acid substitutions
      were observed among the lineages, including seven amino acid differences in
      domains I to III of the envelope protein. Moreover, we dated here, for the first
      time, the introduction of American/Asian genotype into Brazil (lineage BR1) to
      1988/89, followed by the introduction of lineages BR2 (1998-2000) and BR3 (2003
      05). Our results show a delay between the introduction and detection of DENV-2
      lineages in Brazil, reinforcing the importance and need for surveillance programs
      to detect and trace the evolution of these viruses. Additionally, Brazilian DENV
      2 differed in genetic diversity, date of introduction and geographic origin and
      distribution in Brazil, and these are important factors for the evolution,
      dynamics and control of dengue.

PMID- 23533625
TI  - Robot-mediated interviews--how effective is a humanoid robot as a tool for
      interviewing young children?
AB  - Robots have been used in a variety of education, therapy or entertainment
      contexts. This paper introduces the novel application of using humanoid robots
      for robot-mediated interviews. An experimental study examines how children's
      responses towards the humanoid robot KASPAR in an interview context differ in
      comparison to their interaction with a human in a similar setting. Twenty-one
      children aged between 7 and 9 took part in this study. Each child participated in
      two interviews, one with an adult and one with a humanoid robot. Measures include
      the behavioural coding of the children's behaviour during the interviews and
      questionnaire data. The questions in these interviews focused on a special event
      that had recently taken place in the school. The results reveal that the children
      interacted with KASPAR very similar to how they interacted with a human
      interviewer. The quantitative behaviour analysis reveal that the most notable
      difference between the interviews with KASPAR and the human were the duration of
      the interviews, the eye gaze directed towards the different interviewers, and the
      response time of the interviewers. These results are discussed in light of future
      work towards developing KASPAR as an 'interviewer' for young children in
      application areas where a robot may have advantages over a human interviewer,
      e.g. in police, social services, or healthcare applications.

PMID- 23533626
TI  - Interaction between hippocampal and striatal systems predicts subsequent
      consolidation of motor sequence memory.
AB  - The development of fast and reproducible motor behavior is a crucial human
      capacity. The aim of the present study was to address the relationship between
      the implementation of consistent behavior during initial training on a sequential
      motor task (the Finger Tapping Task) and subsequent sleep-dependent motor
      sequence memory consolidation, using functional magnetic resonance imaging (fMRI)
      and total sleep deprivation protocol. Our behavioral results indicated
      significant offline gains in performance speed after sleep whereas performance
      was only stabilized, but not enhanced, after sleep deprivation. At the cerebral
      level, we previously showed that responses in the caudate nucleus increase, in
      parallel to a decrease in its functional connectivity with frontal areas, as
      performance became more consistent. Here, the strength of the competitive
      interaction, assessed through functional connectivity analyses, between the
      caudate nucleus and hippocampo-frontal areas during initial training, predicted
      delayed gains in performance at retest in sleepers but not in sleep-deprived
      subjects. Moreover, during retest, responses increased in the hippocampus and
      medial prefrontal cortex in sleepers whereas in sleep-deprived subjects,
      responses increased in the putamen and cingulate cortex. Our results suggest that
      the strength of the competitive interplay between the striatum and the
      hippocampus, participating in the implementation of consistent motor behavior
      during initial training, conditions subsequent motor sequence memory
      consolidation. The latter process appears to be supported by a reorganisation of
      cerebral activity in hippocampo-neocortical networks after sleep.

PMID- 23533627
TI  - The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global
      chromosome structure and counteracts HP1a and H3K9me2.
AB  - CHD1 is a conserved chromatin remodeling factor that localizes to active genes
      and functions in nucleosome assembly and positioning as well as histone turnover.
      Mouse CHD1 is required for the maintenance of stem cell pluripotency while human
      CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on
      higher order chromatin structure in differentiated cells, we examined the
      consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes
      from salivary glands of third instar Drosophila melanogaster larvae. We observed
      that chromosome structure is sensitive to the amount of this remodeler. Loss of
      CHD1 resulted in alterations of chromosome structure and an increase in the
      heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher
      order chromatin structure and caused a decrease in levels of HP1a. Over
      expression of an ATPase inactive form of CHD1 did not result in severe
      chromosomal defects, suggesting that the ATPase activity is required for this in
      vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate
      with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA
      Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions
      of the genome, it can function to alter the levels of HP1a, perhaps through
      changes in methylation of H3K9.

PMID- 23533628
TI  - Oleic acid and octanoic acid sensing capacity in rainbow trout Oncorhynchus
      mykiss is direct in hypothalamus and Brockmann bodies.
AB  - In a previous study, we provided evidence for the presence in hypothalamus and
      Brockmann bodies (BB) of rainbow trout Oncorhynchus mykiss of sensing systems
      responding to changes in levels of oleic acid (long-chain fatty acid, LCFA) or
      octanoic acid (medium-chain fatty acid, MCFA). Since those effects could be
      attributed to an indirect effect, in the present study, we evaluated in vitro if
      hypothalamus and BB respond to changes in FA in a way similar to that observed in
      vivo. In a first set of experiments, we evaluated in hypothalamus and BB exposed
      to increased oleic acic or octanoic acid concentrations changes in parameters
      related to FA metabolism, FA transport, nuclear receptors and transcription
      factors, reactive oxygen species (ROS) effectors, components of the KATP channel,
      and (in hypothalamus) neuropeptides related to food intake. In a second set of
      experiments, we evaluated in hypothalamus the response of those parameters to
      oleic acid or octanoic acid in the presence of inhibitors of fatty acid sensing
      components. The responses observed in vitro in hypothalamus are comparable to
      those previously observed in vivo and specific inhibitors counteracted in many
      cases the effects of FA. These results support the capacity of rainbow trout
      hypothalamus to directly sense changes in MCFA or LCFA levels. In BB increased
      concentrations of oleic acid or octanoic acid induced changes that in general
      were comparable to those observed in hypothalamus supporting direct FA sensing in
      this tissue. However, those changes were not coincident with those observed in
      vivo allowing us to suggest that the FA sensing capacity of BB previously
      characterized in vivo is influenced by other neuroendocrine systems.

PMID- 23533629
TI  - Leishmania donovani infection induces anemia in hamsters by differentially
      altering erythropoiesis in bone marrow and spleen.
AB  - Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting
      and replicating in macrophages of the bone marrow, spleen, and liver. Severe
      anemia and leucopenia is associated with the disease. Although immune defense
      mechanisms against the parasite have been studied, we have a limited
      understanding of how L. donovani alters hematopoiesis. In this study, we used
      Syrian golden hamsters to investigate effects of L. donovani infection on
      erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks
      post-infection. Anemia was associated with increased levels of serum
      erythropoietin, which indicates the hamsters respond to the anemia by producing
      erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E
      progenitor populations in the spleen and bone marrow and differentially altered
      erythroid gene expression in these organs. In the bone marrow, the mRNA
      expression of erythroid differentiation genes (alpha-globin, beta-globin, ALAS2)
      were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR) and
      transcription factors (GATA1, GATA2, FOG1) were not affected by the infection.
      This suggests that infection has a negative effect on differentiation of
      erythroblasts. In the spleen, erythroid gene expression was enhanced by
      infection, indicating that the anemia activates a stress erythropoiesis response
      in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found
      that IFN-gamma mRNA is highly increased by L. donovani infection. Expression of
      the IFN-gamma inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL),
      was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of
      bone marrow erythroblasts from infected hamsters was examined by flow cytometry.
      Percentage of erythroblasts that were apoptotic was significantly increased by L.
      donovani infection. Together, our results suggest that L. donovani infection
      inhibits erythropoiesis in the bone marrow by cytokine-mediated apoptosis of
      erythroblasts.

PMID- 23533631
TI  - Environmental, institutional, and demographic predictors of environmental
      literacy among middle school children.
AB  - Building environmental literacy (EL) in children and adolescents is critical to
      meeting current and emerging environmental challenges worldwide. Although
      environmental education (EE) efforts have begun to address this need, empirical
      research holistically evaluating drivers of EL is critical. This study begins to
      fill this gap with an examination of school-wide EE programs among middle schools
      in North Carolina, including the use of published EE curricula and time outdoors
      while controlling for teacher education level and experience, student attributes
      (age, gender, and ethnicity), and school attributes (socio-economic status,
      student-teacher ratio, and locale). Our sample included an EE group selected from
      schools with registered school-wide EE programs, and a control group randomly
      selected from NC middle schools that were not registered as EE schools. Students
      were given an EL survey at the beginning and end of the spring 2012 semester. Use
      of published EE curricula, time outdoors, and having teachers with advanced
      degrees and mid-level teaching experience (between 3 and 5 years) were positively
      related with EL whereas minority status (Hispanic and black) was negatively
      related with EL. Results suggest that school-wide EE programs were not associated
      with improved EL, but the use of published EE curricula paired with time outdoors
      represents a strategy that may improve all key components of student EL. Further,
      investments in teacher development and efforts to maintain enthusiasm for EE
      among teachers with more than 5 years of experience may help to boost student EL
      levels. Middle school represents a pivotal time for influencing EL, as
      improvement was slower among older students. Differences in EL levels based on
      gender suggest boys and girls may possess complementary skills sets when
      approaching environmental issues. Our findings suggest ethnicity related
      disparities in EL levels may be mitigated by time spent in nature, especially
      among black and Hispanic students.

PMID- 23533630
TI  - HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic
      reticulum stress and inhibiting autophagy activity in adipocytes.
AB  - BACKGROUND: HIV protease inhibitors (PI) are core components of Highly Active
      Antiretroviral Therapy (HAART), the most effective treatment for HIV infection
      currently available. However, HIV PIs have now been linked to lipodystrophy and
      dyslipidemia, which are major risk factors for cardiovascular disease and
      metabolic syndrome. Our previous studies have shown that HIV PIs activate
      endoplasmic reticulum (ER) stress and disrupt lipid metabolism in hepatocytes and
      macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in
      adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome.
      METHODOLOGY AND PRINCIPAL FINDINGS: Cultured and primary mouse adipocytes and
      human adipocytes were used to examine the effect of frequently used HIV PIs in
      the clinic, lopinavir/ritonavir, on adipocyte differentiation and further
      identify the underlying molecular mechanism of HIV PI-induced dysregulation of
      lipid metabolism in adipocytes. The results indicated that lopinavir alone or in
      combination with ritonavir, significantly activated the ER stress response,
      inhibited cell differentiation, and induced cell apoptosis in adipocytes. In
      addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy
      activity. We also identified through the use of primary adipocytes of CHOP(-/-)
      mice that CHOP, the major transcriptional factor of the ER stress signaling
      pathway, is involved in lopinavir/ritonavir-induced inhibition of cell
      differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress
      appears to be associated with inhibition of autophagy activity in adipocytes.
      CONCLUSION AND SIGNIFICANCE: Activation of ER stress and impairment of autophagy
      activity are involved in HIV PI-induced dysregulation of lipid metabolism in
      adipocytes. The key components of ER stress and autophagy signaling pathways are
      potential therapeutic targets for HIV PI-induced metabolic side effects in HIV
      patients.

PMID- 23533632
TI  - Prognostic role of microRNA-181a/b in hematological malignancies: a meta
      analysis.
AB  - BACKGROUND: Emerging evidence has shown that miRNAs participate in human
      carcinogenesis as tumor suppressors or oncogenes, and have prognostic value for
      patients with cancers. In recent years, the miR-181 family was found dysregulated
      in a variety of human cancers and significantly associated with clinical outcome
      of cancerous patients. MiR-181a and miR-181b (miR-181a/b) were the most
      investigated members in the family. However, the results of miR-181a/b from
      different studies were inconsistent. Therefore, we performed a meta-analysis to
      summarize all the results from available studies, aiming to delineate the
      prognostic role of miR-181a/b in human cancers. METHODS: The identified articles
      were retrieved from the two main on-line databases, PubMed and EMBASE. We
      extracted and estimated the hazard ratios (HRs) for overall survival (OS), which
      compared the high and low expression levels of miR-181a/b in patients of the
      available studies. Each individual HR was used to calculate the pooled HR.
      RESULTS: Eleven studies of 1252 patients were selected into the final meta
      analysis after a strict filtering and qualifying process. Fixed model or random
      model method was chosen depending on the heterogeneity between the studies. The
      subgroup analysis showed that high expressed miR-181a/b could prolong OS in
      patients with hematological malignancies rather than low expression level (HR =
      0.717, P<0.0001). But the expression of miR-181a/b was not significantly relative
      to OS in patients with various cancers (HR = 0.861, p = 0.356). CONCLUSION: Our
      study indicates that the expression level of miR-181a/b is significantly
      associated with OS in hematological malignancies and can be an important clinical
      prognostic factor for those patients.

PMID- 23533633
TI  - CD24 induces expression of the oncomir miR-21 via Src, and CD24 and Src are both
      post-transcriptionally downregulated by the tumor suppressor miR-34a.
AB  - Cancer is a complex disease process that evolves as a consequence of multiple
      malfunctions in key regulatory molecular networks. Understanding these networks
      will be essential to combat cancer. In this study, we focussed on central players
      in such networks. In a series of colon and breast cancer cell lines, we found
      that CD24 activates Src, and induces the activation of c-Jun and expression of c
      Jun and c-Fos. Thereby CD24 increases the promoter activity and expression of miR
      21, which in turn suppresses expression of Pdcd4 and PTEN. Co-transfection of a
      CD24 expression construct and an siRNA that silences Src showed that CD24
      dependent upregulation of miR-21 is mediated by Src. Additionally, we found that
      miR-34a post-transcriptionally downregulates CD24 and Src expression, leading to
      the deactivation of c-Jun, reduced expression of c-Jun and c-Fos, inhibition of
      miR-21, and upregulation of Pdcd4 and PTEN. Furthermore, miR-34a-mediated
      inhibition of Src expression reduced migration and invasion of colorectal cancer
      cells. Resected tumor tissues from 26 colorectal patients showed significantly
      lower expression of Pdcd4 and miR-34a, and higher expression of CD24, Src and miR
      21 compared to the corresponding normal tissues. Moreover, CD24 positively
      correlated with the amount of Src protein in tumor tissues, and a trend towards
      an inverse correlation between miR-34a and Src protein levels was also observed.
      Our results reveal essential players in the complex networks that regulate the
      progression of solid tumors such as colorectal cancer. These findings therefore
      identify novel therapeutic approaches for combating tumor growth and progression.

PMID- 23533634
TI  - Effect of stacked insecticidal Cry proteins from maize pollen on nurse bees (Apis
      mellifera carnica) and their gut bacteria.
AB  - Honey bee pollination is a key ecosystem service to nature and agriculture.
      However, biosafety research on genetically modified crops rarely considers
      effects on nurse bees from intact colonies, even though they receive and
      primarily process the largest amount of pollen. The objective of this study was
      to analyze the response of nurse bees and their gut bacteria to pollen from Bt
      maize expressing three different insecticidal Cry proteins (Cry1A.105, Cry2Ab2,
      and Cry3Bb1). Naturally Cry proteins are produced by bacteria (Bacillus
      thuringiensis). Colonies of Apis mellifera carnica were kept during anthesis in
      flight cages on field plots with the Bt maize, two different conventionally bred
      maize varieties, and without cages, 1-km outside of the experimental maize field
      to allow ad libitum foraging to mixed pollen sources. During their 10-days life
      span, the consumption of Bt maize pollen had no effect on their survival rate,
      body weight and rates of pollen digestion compared to the conventional maize
      varieties. As indicated by ELISA-quantification of Cry1A.105 and Cry3Bb1, more
      than 98% of the recombinant proteins were degraded. Bacterial population sizes in
      the gut were not affected by the genetic modification. Bt-maize, conventional
      varieties and mixed pollen sources selected for significantly different bacterial
      communities which were, however, composed of the same dominant members, including
      Proteobacteria in the midgut and Lactobacillus sp. and Bifidobacterium sp. in the
      hindgut. Surprisingly, Cry proteins from natural sources, most likely B.
      thuringiensis, were detected in bees with no exposure to Bt maize. The natural
      occurrence of Cry proteins and the lack of detectable effects on nurse bees and
      their gut bacteria give no indication for harmful effects of this Bt maize on
      nurse honey bees.

PMID- 23533635
TI  - The association of BAG6 with SGTA and tail-anchored proteins.
AB  - BACKGROUND: The BAG6 protein is a subunit of a heterotrimeric complex that binds
      a range of membrane and secretory protein precursors localized to the cytosol,
      enforcing quality control and influencing their subsequent fate. METHODOLOGY AND
      PRINCIPAL FINDINGS: BAG6 has an N-terminal ubiquitin-like domain, and a C
      terminal Bcl-2-associated athanogene domain, separated by a large central proline
      rich region. We have used in vitro binding approaches to identify regions of BAG6
      important for its interactions with: i) the small-glutamine rich
      tetratricopeptide repeat-containing protein alpha (SGTA) and ii) two model tail
      anchored membrane proteins as a paradigm for its hydrophobic substrates. We show
      that the BAG6-UBL is essential for binding to SGTA, and find that the UBL of a
      second subunit of the BAG6-complex, ubiquitin-like protein 4A (UBL4A), competes
      for SGTA binding. Our data show that this binding is selective, and suggest that
      SGTA can bind either BAG6, or UBL4A, but not both at the same time. We adapted
      our in vitro binding assay to study the association of BAG6 with an immobilized
      tail-anchored protein, Sec61beta, and find both the UBL and BAG domains are
      dispensable for binding this substrate. This conclusion was further supported
      using a heterologous subcellular localization assay in yeast, where the BAG6
      dependent nuclear relocalization of a second tail-anchored protein, GFP-Sed5,
      also required neither the UBL, nor the BAG domain of BAG6. SIGNIFICANCE: On the
      basis of these findings, we propose a working model where the large central
      region of the BAG6 protein provides a binding site for a diverse group of
      substrates, many of which expose a hydrophobic stretch of polypeptide. This
      arrangement would enable the BAG6 complex to bring together its substrates with
      potential effectors including those recruited via its N-terminal UBL. Such
      effectors may include SGTA, and the resulting assemblies influence the subsequent
      fate of the hydrophobic BAG6 substrates.

PMID- 23533636
TI  - Characterization of protective immune responses induced by pneumococcal surface
      protein A in fusion with pneumolysin derivatives.
AB  - Pneumococcal surface protein A (PspA) and Pneumolysin derivatives (Pds) are
      important vaccine candidates, which can confer protection in different models of
      pneumococcal infection. Furthermore, the combination of these two proteins was
      able to increase protection against pneumococcal sepsis in mice. The present
      study investigated the potential of hybrid proteins generated by genetic fusion
      of PspA fragments to Pds to increase cross-protection against fatal pneumococcal
      infection. Pneumolisoids were fused to the N-terminus of clade 1 or clade 2 pspA
      gene fragments. Mouse immunization with the fusion proteins induced high levels
      of antibodies against PspA and Pds, able to bind to intact pneumococci expressing
      a homologous PspA with the same intensity as antibodies to rPspA alone or the co
      administered proteins. However, when antibody binding to pneumococci with
      heterologous PspAs was examined, antisera to the PspA-Pds fusion molecules showed
      stronger antibody binding and C3 deposition than antisera to co-administered
      proteins. In agreement with these results, antisera against the hybrid proteins
      were more effective in promoting the phagocytosis of bacteria bearing
      heterologous PspAs in vitro, leading to a significant reduction in the number of
      bacteria when compared to co-administered proteins. The respective antisera were
      also capable of neutralizing the lytic activity of Pneumolysin on sheep red blood
      cells. Finally, mice immunized with fusion proteins were protected against fatal
      challenge with pneumococcal strains expressing heterologous PspAs. Taken
      together, the results suggest that PspA-Pd fusion proteins comprise a promising
      vaccine strategy, able to increase the immune response mediated by cross-reactive
      antibodies and complement deposition to heterologous strains, and to confer
      protection against fatal challenge.

PMID- 23533637
TI  - Salvianolic acid A, a novel matrix metalloproteinase-9 inhibitor, prevents
      cardiac remodeling in spontaneously hypertensive rats.
AB  - Cardiac fibrosis is a deleterious consequence of hypertension which may further
      advance to heart failure and increased matrix metalloproteinase-9 (MMP-9)
      contributes to the underlying mechanism. Therefore, new therapeutic strategies to
      attenuate the effects of MMP-9 are urgently needed. In the present study, we
      characterize salvianolic acid A (SalA) as a novel MMP-9 inhibitor at molecular,
      cellular and animal level. We expressed a truncated form of MMP-9 which contains
      only the catalytic domain (MMP-9 CD), and used this active protein for enzymatic
      kinetic analysis and Biacore detection. Data generated from these assays
      indicated that SalA functioned as the strongest competitive inhibitor of MMP-9
      among 7 phenolic acids from Salvia miltiorrhiza. In neonatal cardiac fibroblast,
      SalA inhibited fibroblast migration, blocked myofibroblast transformation,
      inhibited secretion of intercellular adhesion molecule (ICAM), interleukin-6 (IL
      6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as collagen
      induced by MMP-9 CD. Functional effects of SalA inhibition on MMP-9 was further
      confirmed in cultured cardiac H9c2 cell overexpressing MMP-9 in vitro and in
      heart of spontaneously hypertensive rats (SHR) in vivo. Moreover, SalA treatment
      in SHR resulted in decreased heart fibrosis and attenuated heart hypertrophy.
      These results indicated that SalA is a novel inhibitor of MMP-9, thus playing an
      inhibitory role in hypertensive fibrosis. Further studies to develop SalA and its
      analogues for their potential clinical application of cardioprotection are
      warranted.

PMID- 23533638
TI  - Long-acting beta2-agonists increase fluticasone propionate-induced mitogen
      activated protein kinase phosphatase 1 (MKP-1) in airway smooth muscle cells.
AB  - Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven
      signalling and plays an important anti-inflammatory role in asthma and airway
      remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP
      mediated signalling, the upregulation of this critical anti-inflammatory protein
      by long-acting beta2-agonists and clinically-used corticosteroids has been
      incompletely examined to date. To address this, we investigated MKP-1 gene
      expression and protein upregulation induced by two long-acting beta2-agonists
      (salmeterol and formoterol), alone or in combination with the corticosteroid
      fluticasone propionate (abbreviated as fluticasone) in primary human airway
      smooth muscle (ASM) cells in vitro. beta2-agonists increased MKP-1 protein in a
      rapid but transient manner, while fluticasone induced sustained upregulation.
      Together, long-acting beta2-agonists increased fluticasone-induced MKP-1 and
      modulated ASM synthetic function (measured by interleukin 6 (IL-6) and
      interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is
      cAMP/adenylate cyclase-mediated, the long-acting beta2-agonist formoterol
      increased IL-6 mRNA expression and secretion. Nevertheless, when added in
      combination with fluticasone, beta2-agonists significantly repressed IL-6
      secretion induced by tumour necrosis factor alpha (TNFalpha). Conversely, as IL-8
      is not cAMP-responsive, beta2-agonists significantly inhibited TNFalpha-induced
      IL-8 in combination with fluticasone, where fluticasone alone was without
      repressive effect. In summary, long-acting beta2-agonists increase fluticasone
      induced MKP-1 in ASM cells and repress synthetic function of this
      immunomodulatory airway cell type.

PMID- 23533639
TI  - TB incidence in an adolescent cohort in South Africa.
AB  - BACKGROUND: Tuberculosis (TB) is a major public health problem globally. Little
      is known about TB incidence in adolescents who are a proposed target group for
      new TB vaccines. We conducted a study to determine the TB incidence rates and
      risk factors for TB disease in a cohort of school-going adolescents in a high TB
      burden area in South Africa. METHODS: We recruited adolescents aged 12 to 18
      years from high schools in Worcester, South Africa. Demographic and clinical
      information was collected, a tuberculin skin test (TST) performed and blood drawn
      for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at
      follow up visits and by surveillance of registers at public sector TB clinics
      over a period of up to 3.8 years after enrolment. RESULTS: A total of 6,363
      adolescents were enrolled (58% of the school population targeted). During follow
      up, 67 cases of bacteriologically confirmed TB were detected giving an overall
      incidence rate of 0.45 per 100 person years (95% confidence interval 0.29-0.72).
      Black or mixed race, maternal education of primary school or less or unknown, a
      positive baseline QuantiFERON assay and a positive baseline TST were significant
      predictors of TB disease on adjusted analysis. CONCLUSION: The adolescent TB
      incidence found in a high burden setting will help TB vaccine developers plan
      clinical trials in this population. Latent TB infection and low socio-economic
      status were predictors of TB disease.

PMID- 23533640
TI  - Efficient posterior probability mapping using Savage-Dickey ratios.
AB  - Statistical Parametric Mapping (SPM) is the dominant paradigm for mass-univariate
      analysis of neuroimaging data. More recently, a bayesian approach termed
      Posterior Probability Mapping (PPM) has been proposed as an alternative. PPM
      offers two advantages: (i) inferences can be made about effect size thus lending
      a precise physiological meaning to activated regions, (ii) regions can be
      declared inactive. This latter facility is most parsimoniously provided by PPMs
      based on bayesian model comparisons. To date these comparisons have been
      implemented by an Independent Model Optimization (IMO) procedure which separately
      fits null and alternative models. This paper proposes a more computationally
      efficient procedure based on Savage-Dickey approximations to the Bayes factor,
      and Taylor-series approximations to the voxel-wise posterior covariance matrices.
      Simulations show the accuracy of this Savage-Dickey-Taylor (SDT) method to be
      comparable to that of IMO. Results on fMRI data show excellent agreement between
      SDT and IMO for second-level models, and reasonable agreement for first-level
      models. This Savage-Dickey test is a bayesian analogue of the classical SPM-F and
      allows users to implement model comparison in a truly interactive manner.

PMID- 23533641
TI  - A leaky-integrator model as a control mechanism underlying flexible decision
      making during task switching.
AB  - The ability to switch between tasks is critical for animals to behave according
      to context. Although the association between the prefrontal cortex and task
      switching has been well documented, the ultimate modulation of sensory-motor
      associations has yet to be determined. Here, we modeled the results of a previous
      study showing that task switching can be accomplished by communication from
      distinct populations of sensory neurons. We proposed a leaky-integrator model
      where relevant and irrelevant information were stored separately in two
      integrators and task switching was achieved by leaking information from the
      irrelevant integrator. The model successfully explained both the behavioral and
      neuronal data. Additionally, the leaky-integrator model showed better performance
      than an alternative model, where irrelevant information was discarded by
      decreasing the weight on irrelevant information, when animals initially failed to
      commit to a task. Overall, we propose that flexible switching is, in part,
      achieved by actively controlling the amount of leak of relevant and irrelevant
      information.

PMID- 23533642
TI  - Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague
      Dawley rats aged up to eight months.
AB  - Excessive exposure to alcohol prenatally has a myriad of detrimental effects on
      the health and well-being of the offspring. It is unknown whether chronic low
      moderate exposure of alcohol prenatally has similar and lasting effects on the
      adult offspring's health. Using our recently developed Sprague-Dawley rat model
      of 6% chronic prenatal ethanol exposure, this study aimed to determine if this
      modest level of exposure adversely affects glucose homeostasis in male and female
      offspring aged up to eight months. Plasma glucose concentrations were measured in
      late fetal and postnatal life. The pancreas of 30 day old offspring was analysed
      for beta-cell mass. Glucose handling and insulin action was measured at four
      months using an intraperitoneal glucose tolerance test and insulin challenge,
      respectively. Body composition and metabolic gene expression were measured at
      eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed
      fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were
      normoglycaemic and normoinsulinaemic under basal fasting conditions and had
      normal pancreatic beta-cell mass at postnatal day 30. However, during a glucose
      tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with
      increased first phase insulin secretion. Female ethanol-exposed offspring
      displayed enhanced glucose clearance during an insulin challenge. Body
      composition and hepatic, muscle and adipose tissue metabolic gene expression
      levels at eight months were not altered by prenatal ethanol exposure. Low
      moderate chronic prenatal ethanol exposure has subtle, sex specific effects on
      glucose homeostasis in the young adult rat. As aging is associated with glucose
      dysregulation, further studies will clarify the long lasting effects of prenatal
      ethanol exposure.

PMID- 23533643
TI  - Genome-wide microarrray analysis reveals roles for the REF-1 family member HLH-29
      in ferritin synthesis and peroxide stress response.
AB  - In Caenorhabditis elegans, the six proteins that make up the REF-1 family have
      been identified as functional homologs of the Hairy/Enhancer of Split (HES)
      proteins. These transcription factors act in both Notch dependent and Notch
      independent pathways to regulate embryonic events during development; however,
      their post-embryonic functions are not well defined. As a first step toward
      understanding how the REF-1 family works together to coordinate post-embryonic
      events, we used gene expression microarray analysis to identify transcriptional
      targets of HLH-29 in L4/young adult stage animals. Here we show that HLH-29
      targets are genes needed for the regulation of growth and lifespan, including
      genes required for oxidative stress response and fatty acid metabolism, and the
      ferritin genes, ftn-1 and ftn-2. We show that HLH-29 regulates ftn-1 expression
      via promoter sequences upstream of the iron-dependent element that is recognized
      by the hypoxia inducible factor, HIF-1. Additionally, hlh-29 mutants are more
      resistant to peroxide stress than wild-type animals and ftn-1(RNAi) animals, even
      in the presence of excess iron. Finally we show that HLH-29 acts parallel to DAF
      16 but upstream of the microphthalmia transcription factor ortholog, HLH-30, to
      regulate ftn-1 expression under normal growth conditions.

PMID- 23533644
TI  - Brain areas controlling heart rate variability in tinnitus and tinnitus-related
      distress.
AB  - BACKGROUND: Tinnitus is defined as an intrinsic sound perception that cannot be
      attributed to an external sound source. Distress in tinnitus patients is related
      to increased beta activity in the dorsal part of the anterior cingulate and the
      amount of distress correlates with network activity consisting of the amygdala
      anterior cingulate cortex-insula-parahippocampus. Previous research also revealed
      that distress is associated to a higher sympathetic (OS) tone in tinnitus
      patients and tinnitus suppression to increased parasympathetic (PS) tone.
      METHODOLOGY: The aim of the present study is to investigate the relationship
      between tinnitus distress and the autonomic nervous system and find out which
      cortical areas are involved in the autonomic nervous system influences in
      tinnitus distress by the use of source localized resting state
      electroencephalogram (EEG) recordings and electrocardiogram (ECG). Twenty-one
      tinnitus patients were included in this study. CONCLUSIONS: The results indicate
      that the dorsal and subgenual anterior cingulate, as well as the left and right
      insula are important in the central control of heart rate variability in tinnitus
      patients. Whereas the sympathovagal balance is controlled by the subgenual and
      pregenual anterior cingulate cortex, the right insula controls sympathetic
      activity and the left insula the parasympathetic activity. The perceived distress
      in tinnitus patients seems to be sympathetically mediated.

PMID- 23533645
TI  - Lifetime costs and outcomes of repair of Tetralogy of Fallot compared to natural
      progression of the disease: Great Ormond Street Hospital cohort.
AB  - BACKGROUND: Tetralogy of Fallot is a congenital heart disease that requires
      surgical repair without which survival through childhood is extremely rare. The
      aim of this paper is to use data from the mandatory follow-up of patients with
      Tetralogy of Fallot to model the health-related costs and outcomes over the first
      55-years of life. METHOD: A decision analytical model was developed to establish
      costs and outcomes for patients up to 55 years after diagnosis and first repair
      of Tetralogy of Fallot compared to natural progression. Data from Adult
      Congenital Heart Disease (ACHD) centres that follow up Tetralogy of Fallot
      patients and Great Ormond Street Hospital (GOSH), London, United Kingdom (UK)
      medical records was used to establish the cost and effectiveness of current
      interventions. Data from a Czech cohort was used for the natural, no intervention
      condition. RESULTS: The average cost per patient of a repair for Tetralogy of
      Fallot was L26,938 (SE = L4,140). The full life time cost per patient, with no
      discount rate, was L65,310 (95% CI L64,981-L65,729); L56,559 discounted (95% CI
      L56,159-L56,960). Patients with a repair had an average of 35 Quality Adjusted
      Life Years (QALYs) per patient over 55 years undiscounted and 20.16 QALYs
      discounted. If the disorder was left to take its natural course, patients on
      average had a total of 3 QALYs per patient with no discount rate and 2.30 QALYs
      discounted. CONCLUSION: A model has been developed that provides an estimate of
      the value for money of an expensive repair of a congenital heart disease. The
      model could be used to test the cost-effectiveness of making amendments to the
      care pathway.

PMID- 23533646
TI  - Immunogenic and invasive properties of Brucella melitensis 16M outer membrane
      protein vaccine candidates identified via a reverse vaccinology approach.
AB  - Brucella is the etiologic agent of brucellosis, one of the most common and widely
      distributed zoonotic diseases. Its highly infectious nature, the insidious,
      systemic, chronic, debilitating aspects of the disease and the lack of an
      approved vaccine for human use in the United States are features that make
      Brucella a viable threat to public health. One of the main impediments to vaccine
      development is identification of suitable antigens. In order to identify antigens
      that could potentially be used in a vaccine formulation, we describe a multi-step
      antigen selection approach. We initially used an algorithm (Vaxign) to predict
      ORF encoding outer membrane proteins with antigenic determinants. Differential
      gene expression during acute infection and published evidence for a role in
      virulence were used as criteria for down-selection of the candidate antigens that
      resulted from in silico prediction. This approach resulted in the identification
      of nine Brucella melitensis outer membrane proteins, 5 of which were
      recombinantly expressed and used for validation. Omp22 and Hia had the highest in
      silico scores for adhesin probability and also conferred invasive capacity to E.
      coli overexpressing recombinant proteins. With the exception of FlgK in the goat,
      all proteins reacted to pooled sera from exposed goats, mice, and humans. BtuB,
      Hia and FlgK stimulated a mixed Th1-Th2 response in splenocytes from immunized
      mice while BtuB and Hia elicited NO release from splenocytes of S19 immunized
      mice. The results support the applicability of the current approach to the
      identification of antigens with immunogenic and invasive properties. Studies to
      assess immunogenicity and protective efficacy of individual proteins in the mouse
      are currently underway.

PMID- 23533647
TI  - Polymorphisms in the calcium-sensing receptor gene are associated with clinical
      outcome of neuroblastoma.
AB  - BACKGROUND: Neuroblastic tumors include the neuroblastomas,
      ganglioneuroblastomas, and ganglioneuromas. Clinical behavior of these
      developmental malignancies varies from regression to aggressive growth with
      metastatic dissemination. Several clinical, histological, genetic, and biological
      features are associated with this diversity of clinical presentations. The
      calcium-sensing receptor (CaSR) is a G-protein coupled receptor with a key role
      in calcium homeostasis. We have previously reported that it is expressed in
      benign, differentiated neuroblastic tumors, but silenced by genetic and
      epigenetic events in unfavorable neuroblastomas. We have now analyzed three
      functionally relevant polymorphisms clustered at the signal transduction region
      of the CaSR (rs1801725, rs1042636 and rs1801726) to assess if genetic variants
      producing a less active receptor are associated with more aggressive disease
      course. METHODS: Polymorphisms were analyzed in DNA samples from 65 patients
      using specific Taqman Genotyping Assays. RESULTS: Mildly inactivating variant
      rs1801725 was associated with clinical stage 4 (P = 0.002) and the histological
      subgroup of undifferentiated neuroblastomas (P = 0.046). Patients harboring this
      polymorphism had significantly lower overall (P = 0.022) and event-free survival
      (P = 0.01) rates than those who were homozygous for the most common allele among
      Caucasians. However, this single locus genotype was not independently associated
      with outcome in multivariate analyses. Conversely, the tri-locus haplotype TAC
      was independently associated with an increased risk of death in the entire cohort
      (Hazard Ratio = 2.45; 95% Confidence Interval [1.14-5.29]; P = 0.022) and also in
      patients diagnosed with neuroblastomas (Hazard Ratio = 2.74; 95% Confidence
      Interval [1.20-6.25]; P = 0.016). CONCLUSIONS: The TAC haplotype includes the
      moderately inactivating variant rs1801725 and absence of the gain-of-function
      rs1042636 polymorphism. Thus, its association with metastatic disease and poor
      outcome would add to our previous data and further support that inactivation of
      the CaSR gene is a mechanism associated with neuroblastoma malignant behavior.

PMID- 23533648
TI  - Prevalence of human papillomavirus in 5,072 consecutive cervical SurePath samples
      evaluated with the Roche cobas HPV real-time PCR assay.
AB  - New commercially available Human Papillomavirus (HPV) assays need to be evaluated
      in a variety of cervical screening settings. Cobas HPV Test (cobas) is a real
      time PCR-based assay allowing for separate detection of HPV genotypes 16 and 18
      and a bulk of 12 other high-risk genotypes. The aim of the present study,
      Horizon, was to assess the prevalence of high-risk HPV infections in an area with
      a high background risk of cervical cancer, where women aged 23-65 years are
      targeted for cervical screening. We collected 6,258 consecutive cervical samples
      from the largest cervical screening laboratory in Denmark serving the whole of
      Copenhagen. All samples were stored in SurePath media. In total, 5,072 samples
      were tested with cobas, Hybrid Capture 2 High Risk HPV DNA test (HC2) and liquid
      based cytology. Of these, 27% tested positive on cobas. This proportion decreased
      by age, being 43% in women aged 23-29 years and 10% in women aged 60-65 years.
      HC2 assay was positive in 20% of samples, and cytology was abnormal (>= atypical
      squamous cells of undetermined significance) for 7% samples. When only samples
      without recent abnormalities were taken into account, 24% tested positive on
      cobas, 19% on HC2, and 5% had abnormal cytology. The proportion of positive cobas
      samples was higher than in the ATHENA trial. The age-standardized cobas
      positivity vs. cytology abnormality was 3.9 in our study and 1.7 in ATHENA. If in
      Copenhagen the presently used cytology would be replaced by cobas in women above
      age 30 years, an extra 11% of women would based on historical data be expected to
      have a positive cobas test without an underlying cervical intraepithelial lesion
      grade 3 or worse. Countries with a high prevalence of HPV infections should
      therefore proceed to primary HPV-based cervical screening with caution.

PMID- 23533649
TI  - BRG1 is a prognostic marker and potential therapeutic target in human breast
      cancer.
AB  - BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been
      implicated in cancer development; however, the biological significance of BRG1 in
      breast cancer remains unknown. We explored the role of BRG1 in human breast
      cancer pathogenesis. Using tissue microarray and immunohistochemistry, we
      evaluated BRG1 staining in 437 breast cancer specimens and investigated its role
      in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier
      survival curves showed that high BRG1 expression is inversely correlated with
      both overall (P = 0.000) and disease-specific (P = 0.000) 5-year patient
      survival. Furthermore, we found that knockdown of BRG1 by RNA interference
      markedly inhibits cell proliferation and causes cessation of cell cycle. This
      reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E
      are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the
      expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells
      to migrate and to invade. These results highlight the importance of BRG1 in
      breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a
      potentially selective therapeutic target.

PMID- 23533650
TI  - Neutralizing antibody responses in macaques induced by human immunodeficiency
      virus type 1 monovalent or trivalent envelope glycoproteins.
AB  - A major goal of efforts to develop a vaccine to prevent HIV-1 infection is
      induction of broadly cross-reactive neutralizing antibodies (bcnAb). In previous
      studies we have demonstrated induction of neutralizing antibodies that did cross
      react among multiple primary and laboratory strains of HIV-1, but neutralized
      with limited potency. In the present study we tested the hypothesis that
      immunization with multiple HIV-1 envelope glycoproteins (Envs) would result in a
      more potent and cross-reactive neutralizing response. One Env, CM243(N610Q), was
      selected on the basis of studies of the effects of single and multiple mutations
      of the four gp41 glycosylation sites. The other two Envs included R2 (subtype B)
      and 14/00/4 (subtype F), both of which were obtained from donors with bcnAb.
      Rhesus monkeys were immunized using a prime boost regimen as in previous studies.
      Individual groups of monkeys were immunized with either one of the three Envs or
      all three. The single N610Q and N615Q mutations of CM243 Env did not disrupt
      protein secretion, processing into, or reactivity with mAbs, unlike other single
      or multiple deglycosylation mutations. In rabbit studies the N610Q mutation alone
      or in combination was associated with an enhanced neutralizing response against
      homologous and heterologous subtype E viruses. In the subsequent monkey study the
      response induced by the R2 Env regimen was equivalent to the trivalent regimen
      and superior to the other monovalent regimens against the virus panel used for
      testing. The 14/00/4 Env induced responses superior to CM243(N610Q). The results
      indicate that elimination of the glycosylation site near the gp41 loop results in
      enhanced immunogenicity, but that immunization of monkeys with these three
      distinct Envs was not more immunogenic than with one.

PMID- 23533651
TI  - Cryo-EM structure of a novel calicivirus, Tulane virus.
AB  - Tulane virus (TV) is a newly isolated cultivatable calicivirus that infects
      juvenile rhesus macaques. Here we report a 6.3 A resolution cryo-electron
      microscopy structure of the TV virion. The TV virion is about 400 A in diameter
      and consists of a T = 3 icosahedral protein capsid enclosing the RNA genome. 180
      copies of the major capsid protein VP1 (~57 KDa) are organized into two types of
      dimers A/B and C/C and form a thin, smooth shell studded with 90 dimeric
      protrusions. The overall capsid organization and the capsid protein fold of TV
      closely resemble that of other caliciviruses, especially of human Norwalk virus,
      the prototype human norovirus. These close structural similarities support TV as
      an attractive surrogate for the non-cultivatable human noroviruses. The most
      distinctive feature of TV is that its C/C dimers are in a highly flexible
      conformation with significantly reduced interactions between the shell (S) domain
      and the protruding (P) domain of VP1. A comparative structural analysis indicated
      that the P domains of TV C/C dimers were much more flexible than those of other
      caliciviruses. These observations, combined with previous studies on other
      caliciviruses, led us to hypothesize that the enhanced flexibility of C/C dimer P
      domains are likely required for efficient calicivirus-host cell interactions and
      the consequent uncoating and genome release. Residues in the S-P1 hinge between
      the S and P domain may play a critical role in the flexibility of P domains of
      C/C dimers.

PMID- 23533653
TI  - Preference and performance in plant-herbivore interactions across latitude--a
      study in U.S. Atlantic salt marshes.
AB  - High-latitude plants are often more palatable to herbivores than low-latitude
      conspecifics. Does increased plant palatability lead to better herbivore
      performance? Our field and laboratory work investigated (A) whether high-latitude
      plants have traits indicating that they should be higher-quality foods for
      herbivores; (B) whether geographic differences in plant quality are more
      important than local adaptation of herbivores. We studied 3 plant species and 6
      invertebrate herbivores in U.S. Atlantic Coast. Past studies had shown high
      latitude individuals of these plants are more palatable than low-latitude
      conspecifics. We documented plant traits and herbivore performance (body size) in
      the field across latitude. We collected individuals from different latitudes for
      factorial (plant region x herbivore region) laboratory experiments, examining how
      herbivore performance was affected by plant region, herbivore region, and their
      interaction (i.e., local adaptation). Field surveys suggested high-latitude
      plants were likely of higher quality to herbivores. Leaf nitrogen content in all
      plant species increased toward high latitudes, consistent with lower leaf C/N and
      higher leaf chlorophyll content at high latitudes. Furthermore, leaf toughness
      decreased toward higher latitudes in 1 species. The body size of 4 herbivore
      species increased with latitude, consistent with high-latitude leaves being of
      higher quality, while 2 grasshopper species showed the opposite pattern, likely
      due to life-history constraints. In the laboratory, high-latitude plants
      supported better performance in 4 herbivore species (marginal in the 5th). The
      geographic region where herbivores were collected affected herbivore performance
      in all 6 species; however, the pattern was mixed, indicating a lack of local
      adaptation by herbivores to plants from their own geographic region. Our results
      suggest that more-palatable plants at high latitudes support better herbivore
      growth. Given that geographic origin of either plants or herbivores can affect
      herbivore performance, the nature of plant-herbivore interactions is likely to
      change if climate change "reshuffles" plant and herbivore populations across
      latitude.

PMID- 23533652
TI  - Confirmation of the reported association of clonal chromosomal mosaicism with an
      increased risk of incident hematologic cancer.
AB  - Chromosomal abnormalities provide clinical utility in the diagnosis and treatment
      of hematologic malignancies, and may be predictive of malignant transformation in
      individuals without apparent clinical presentation of a hematologic cancer. In an
      effort to confirm previous reports of an association between clonal mosaicism and
      incident hematologic cancer, we applied the anomDetectBAF algorithm to call
      chromosomal anomalies in genotype data from previously conducted Genome Wide
      Association Studies (GWAS). The genotypes were initially collected from DNA
      derived from peripheral blood of 12,176 participants in the Group Health
      electronic Medical Records and Genomics study (eMERGE) and the Women's Health
      Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and
      large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of
      clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple
      myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5
      fold increased risk (95% CI: 3.3-9.3; p-value = 7.5*10(-11)) of developing these
      cancers subsequently. Carriers of large mosaic anomalies showed particularly
      pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9-41.6; p-value =
      7.3*10(-14)). Thus we independently confirm the association between detectable
      clonal mosaicism and hematologic cancer found previously in two recent
      publications.

PMID- 23533654
TI  - Dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235
      has a therapeutic potential and sensitizes cisplatin in nasopharyngeal carcinoma.
AB  - Phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin inhibitor
      (mTOR) pathway is often constitutively activated in human tumor cells and thus
      has been considered as a promising drug target. To ascertain a therapeutical
      approach of nasopharyngeal carcinoma (NPC), we hypothesized NVP-BEZ235, a novel
      and potent imidazo[4,5-c] quinolone derivative, that dually inhibits both PI3K
      and mTOR kinases activities, had antitumor activity in NPC. Expectedly, we found
      that NVP-BEZ235 selectively inhibited proliferation of NPC cells rather than
      normal nasopharyngeal cells using MTT assay. In NPC cell lines, with the extended
      exposure, NVP-BEZ235 selectively inhibited proliferation of NPC cells harboring
      PIK3CA mutation, compared to cells with wild-type PIK3CA. Furthermore, exposure
      of NPC cells to NVP-BEZ235 resulted in G1 growth arrest by Propidium iodide
      uptake assay, reduction of cyclin D1and CDK4, and increased levels of P27 and P21
      by Western blotting, but negligible apoptosis. Moreover, we found that cisplatin
      (CDDP) activated PI3K/AKT and mTORC1 pathways and NVP-BEZ235 alleviated the
      activation by CDDP through dually targeting PI3K and mTOR kinases. Also, NVP
      BEZ235 combining with CDDP synergistically inhibited proliferation and induced
      apoptosis in NPC cells. In CNE2 and HONE1 nude mice xenograft models, orally NVP
      BEZ235 efficiently attenuated tumor growth with no obvious toxicity. In
      combination with NVP-BEZ235 and CDDP, there was dramatic synergy in shrinking
      tumor volumes and inducing apoptosis through increasing Noxa, Bax and decreasing
      Mcl-1, Bcl-2. Based on the above results, NVP-BEZ235, which has entered phase
      I/II clinical trials in patients with advanced solid tumors, has a potential as a
      monotherapy or in combination with CDDP for NPC treatment.

PMID- 23533655
TI  - Barriers and facilitators of participation in sports: a qualitative study on
      Dutch individuals with lower limb amputation.
AB  - INTRODUCTION: Although individuals with lower limb amputation may benefit from
      participation in sports, less than 40% do so. AIM: To identify the barriers and
      facilitators that influence participation in sports for individuals with lower
      limb amputation. DESIGN: Qualitative study. PARTICIPANTS: Twenty six individuals
      with lower limb amputation, all originating from the Dutch provinces of Groningen
      and Drenthe, of which 13 athletes. METHODS: Semi-structured interviews were used
      to gather information. Following thematic analysis, emerging themes were
      organized in three categories Technical, Social and Personal. RESULTS: Sport was
      perceived as enjoyable activity that would help participants to become and stay
      healthy, improve the number of social contacts, reduce phantom pain and decrease
      daily tension. Inadequate facilities, problematic transportation, trivialization
      from others, poor health and lack of motivation or the lack of a sports partner
      were barriers commonly mentioned by non-athletes. Remarkably, while all athletes
      were successful prosthetic users, the majority chose to participate in sports for
      which prosthesis was neither required nor needed. CONCLUSIONS: Each individual
      with lower limb amputation needs to be counselled according to the barriers and
      facilitators he/she personally experiences. Athletes appeared to be more
      proactive in searching for a solution and also appeared less discouraged by
      failing.

PMID- 23533656
TI  - Establishment of immortalized human erythroid progenitor cell lines able to
      produce enucleated red blood cells.
AB  - Transfusion of red blood cells (RBCs) is a standard and indispensable therapy in
      current clinical practice. In vitro production of RBCs offers a potential means
      to overcome a shortage of transfusable RBCs in some clinical situations and also
      to provide a source of cells free from possible infection or contamination by
      microorganisms. Thus, in vitro production of RBCs may become a standard procedure
      in the future. We previously reported the successful establishment of
      immortalized mouse erythroid progenitor cell lines that were able to produce
      mature RBCs very efficiently. Here, we have developed a reliable protocol for
      establishing immortalized human erythroid progenitor cell lines that are able to
      produce enucleated RBCs. These immortalized cell lines produce functional
      hemoglobin and express erythroid-specific markers, and these markers are
      upregulated following induction of differentiation in vitro. Most importantly,
      these immortalized cell lines all produce enucleated RBCs after induction of
      differentiation in vitro, although the efficiency of producing enucleated RBCs
      remains to be improved further. To the best of our knowledge, this is the first
      demonstration of the feasibility of using immortalized human erythroid progenitor
      cell lines as an ex vivo source for production of enucleated RBCs.

PMID- 23533657
TI  - Regulation and function of TRPM7 in human endothelial cells: TRPM7 as a potential
      novel regulator of endothelial function.
AB  - TRPM7, a cation channel of the transient receptor potential channel family, has
      been identified as a ubiquitous magnesium transporter. We here show that TRPM7 is
      expressed in endothelial cells isolated from the umbilical vein (HUVEC), widely
      used as a model of macrovascular endothelium. Quiescence and senescence do not
      modulate TRPM7 amounts, whereas oxidative stress generated by the addition of
      hydrogen peroxide increases TRPM7 levels. Moreover, high extracellular magnesium
      decreases the levels of TRPM7 by activating calpains, while low extracellular
      magnesium, known to promote endothelial dysfunction, stimulates TRPM7
      accumulation partly through the action of free radicals. Indeed, the antioxidant
      trolox prevents TRPM7 increase by low magnesium. We also demonstrate the unique
      behaviour of HUVEC in responding to pharmacological and genetic inhibition of
      TRPM7 with an increase of cell growth and migration. Our results indicate that
      TRPM7 modulates endothelial behavior and that any condition leading to TRPM7
      upregulation might impair endothelial function.

PMID- 23533658
TI  - Embryonic carcinoma cells show specific dielectric resistance profiles during
      induced differentiation.
AB  - Induction of differentiation in cancer stem cells by drug treatment represents an
      important approach for cancer therapy. The understanding of the mechanisms that
      regulate such a forced exit from malignant pluripotency is fundamental to enhance
      our knowledge of tumour stability. Certain nucleoside analogues, such as 2'-deoxy
      5-azacytidine and 1beta-arabinofuranosylcytosine, can induce the differentiation
      of the embryonic cancer stem cell line NTERA 2 D1 (NT2). Such induced
      differentiation is associated with drug-dependent DNA-damage, cellular stress and
      the proteolytic depletion of stem cell factors. In order to further elucidate the
      mode of action of these nucleoside drugs, we monitored differentiation-specific
      changes of the dielectric properties of growing NT2 cultures using electric cell
      substrate impedance sensing (ECIS). We measured resistance values of untreated
      and retinoic acid treated NT2 cells in real-time and compared their impedance
      profiles to those of cell populations triggered to differentiate with several
      established substances, including nucleoside drugs. Here we show that treatment
      with retinoic acid and differentiation-inducing drugs can trigger specific,
      concentration-dependent changes in dielectric resistance of NT2 cultures, which
      can be observed as early as 24 hours after treatment. Further, low concentrations
      of nucleoside drugs induce differentiation-dependent impedance values comparable
      to those obtained after retinoic acid treatment, whereas higher concentrations
      induce proliferation defects. Finally, we show that impedance profiles of
      substance-induced NT2 cells and those triggered to differentiate by depletion of
      the stem cell factor OCT4 are very similar, suggesting that reduction of OCT4
      levels has a dominant function for differentiation induced by nucleoside drugs
      and retinoic acid. The data presented show that NT2 cells have specific
      dielectric properties, which allow the early identification of differentiating
      cultures and real-time label-free monitoring of differentiation processes. This
      work might provide a basis for further analyses of drug candidates for
      differentiation therapy of cancers.

PMID- 23533659
TI  - Effects of management intervention on post-disturbance community composition: an
      experimental analysis using bayesian hierarchical models.
AB  - As human demand for ecosystem products increases, management intervention may
      become more frequent after environmental disturbances. Evaluations of ecological
      responses to cumulative effects of management interventions and natural
      disturbances provide critical decision-support tools for managers who strive to
      balance environmental conservation and economic development. We conducted an
      experiment to evaluate the effects of salvage logging on avian community
      composition in lodgepole pine (Pinus contorta) forests affected by beetle
      outbreaks in Oregon, USA, 1996-1998. Treatments consisted of the removal of
      lodgepole pine snags only, and live trees were not harvested. We used a bayesian
      hierarchical model to quantify occupancy dynamics for 27 breeding species, while
      accounting for variation in the detection process. We examined how magnitude and
      precision of treatment effects varied when incorporating prior information from a
      separate intervention study that occurred in a similar ecological system.
      Regardless of which prior we evaluated, we found no evidence that the harvest
      treatment had a negative impact on species richness, with an estimated average of
      0.2-2.2 more species in harvested stands than unharvested stands. Estimated
      average similarity between control and treatment stands ranged from 0.82-0.87 (1
      indicating complete similarity between a pair of stands) and suggested that
      treatment stands did not contain novel assemblies of species responding to the
      harvesting prescription. Estimated treatment effects were positive for twenty
      four (90%) of the species, although the credible intervals contained 0 in all
      cases. These results suggest that, unlike most post-fire salvage logging
      prescriptions, selective harvesting after beetle outbreaks may meet multiple
      management objectives, including the maintenance of avian community richness
      comparable to what is found in unharvested stands. Our results provide managers
      with prescription alternatives to respond to severe beetle outbreaks that
      continue to occur across extensive portions of the dry forests of western North
      America.

PMID- 23533660
TI  - Ectopic expression of Arabidopsis glycosyltransferase UGT85A5 enhances salt
      stress tolerance in tobacco.
AB  - Abiotic stresses greatly influence plant growth and productivity. While
      glycosyltransferases are widely distributed in plant kingdom, their biological
      roles in response to abiotic stresses are largely unknown. In this study, a novel
      Arabidopsis glycosyltransferase gene UGT85A5 was identified as significantly
      induced by salt stress. Ectopic expression of UGT85A5 in tobacco enhanced the
      salt stress tolerance in the transgenic plants. There were higher seed
      germination rates, better plant growth and less chlorophyll loss in transgenic
      lines compared to wild type plants under salt stress. This enhanced tolerance of
      salt stress was correlated with increased accumulations of proline and soluble
      sugars, but with decreases in malondialdehyde accumulation and Na(+)/K(+) ratio
      in UGT85A5-expressing tobacco. Furthermore, during salt stress, expression of
      several carbohydrate metabolism-related genes including those for sucrose
      synthase, sucrose-phosphate synthase, hexose transporter and a group2 LEA protein
      were obviously upregulated in UGT85A5-expressing transgenic plants compared with
      wild type controls. Thus, these findings suggest a specific protective role of
      this glycosyltransferase against salt stress and provide a genetic engineering
      strategy to improve salt tolerance of crops.

PMID- 23533661
TI  - ZBED evolution: repeated utilization of DNA transposons as regulators of diverse
      host functions.
AB  - ZBED genes originate from domesticated hAT DNA transposons and encode regulatory
      proteins of diverse function in vertebrates. Here we reveal the evolutionary
      relationship between ZBED genes and demonstrate that they are derived from at
      least two independent domestication events in jawed vertebrate ancestors. We show
      that ZBEDs form two monophyletic clades, one of which has expanded through
      several independent duplications in host lineages. Subsequent diversification of
      ZBED genes has facilitated regulation of multiple diverse fundamental functions.
      In contrast to known examples of transposable element exaptation, our results
      demonstrate a novel unprecedented capacity for the repeated utilization of a
      family of transposable element-derived protein domains sequestered as regulators
      during the evolution of diverse host gene functions in vertebrates. Specifically,
      ZBEDs have contributed to vertebrate regulatory innovation through the donation
      of modular DNA and protein interacting domains. We identify that C7ORF29, ZBED2,
      3, 4, and ZBEDX form a monophyletic group together with ZBED6, that is distinct
      from ZBED1 genes. Furthermore, we show that ZBED5 is related to Buster DNA
      transposons and is phylogenetically separate from other ZBEDs. Our results offer
      new insights into the evolution of regulatory pathways, and suggest that DNA
      transposons have contributed to regulatory complexity during genome evolution in
      vertebrates.

PMID- 23533662
TI  - Estimation of quasi-stiffness of the human knee in the stance phase of walking.
AB  - Biomechanical data characterizing the quasi-stiffness of lower-limb joints during
      human locomotion is limited. Understanding joint stiffness is critical for
      evaluating gait function and designing devices such as prostheses and orthoses
      intended to emulate biological properties of human legs. The knee joint moment
      angle relationship is approximately linear in the flexion and extension stages of
      stance, exhibiting nearly constant stiffnesses, known as the quasi-stiffnesses of
      each stage. Using a generalized inverse dynamics analysis approach, we identify
      the key independent variables needed to predict knee quasi-stiffness during
      walking, including gait speed, knee excursion, and subject height and weight.
      Then, based on the identified key variables, we used experimental walking data
      for 136 conditions (speeds of 0.75-2.63 m/s) across 14 subjects to obtain best
      fit linear regressions for a set of general models, which were further simplified
      for the optimal gait speed. We found R(2) > 86% for the most general models of
      knee quasi-stiffnesses for the flexion and extension stages of stance. With only
      subject height and weight, we could predict knee quasi-stiffness for preferred
      walking speed with average error of 9% with only one outlier. These results
      provide a useful framework and foundation for selecting subject-specific
      stiffness for prosthetic and exoskeletal devices designed to emulate biological
      knee function during walking.

PMID- 23533663
TI  - Syndecan binding protein (SDCBP) is overexpressed in estrogen receptor negative
      breast cancers, and is a potential promoter for tumor proliferation.
AB  - BACKGROUND: Syndecan binding protein (SDCBP), an adapter protein containing PDZ
      domains, contributes to the tumorigenicity and metastasis of many malignant
      tumors, such as malignant melanoma. Our study aimed in revealing the expression
      profile of SDCBP in breast cancer (BCa) and its role in tumor cell proliferation,
      and then exploring its value in the targeted treatment of BCa.
      METHODOLOGY/PRINCIPAL FINDINGS: We first evaluated the SDCBP expression by
      immunohistochemistry in normal breast and BCa tissues. Then we explored the
      expression profile of SDCBP in different BCa cell lines. By constructing SDCBP
      silenced BCa cell clones, we further assessed the effects of SDCBP suppression on
      tumor cells in vitro by cell culture and in vivo by tumorigenicity. SDCBP
      expression was detected in 80.6% (n = 160) of BCa tissues, in contrast to its
      expression in 13% (n = 23) of normal breast tissues (P<0.001). Among the tumors,
      the level of its expression was positively correlated with histological grade and
      tumor staging while negatively correlated with the estrogen receptor (ER)
      expression. Higher expression of SDCBP was also noted in ER-negative BCa cell
      lines. It was also identified that SDCBP expression was down-regulated in a dose
      dependent mode by 17-beta estradiol in estrogen-responsive MCF-7. Furthermore,
      SDCBP silence inhibited ER-negative tumor cell growth in vivo and in vitro. Cell
      cycle studies showed that SDCBP silence increased G1 cell population and resulted
      in related cell-cycle-regulator changes: up-regulation of p21 and p27 while down
      regulation of cyclin E. CONCLUSION/SIGNIFICANCE: Our results suggested that SDCBP
      played an important role in tumor growth of ER-negative BCas. In these tumors
      where the estrogen signaling pathway is not available, SDCBP probably contribute
      to tumor growth through an alternative signaling pathway by promoting tumor cells
      passing the G1/S checkpoint into the cell cycle. Suppression of SDCBP expression
      may have its potential to become a targeted therapy for ER-negative BCas.

PMID- 23533664
TI  - Resveratrol induces premature senescence in lung cancer cells via ROS-mediated
      DNA damage.
AB  - Resveratrol (RV) is a natural component of red wine and grapes that has been
      shown to be a potential chemopreventive and anticancer agent. However, the
      molecular mechanisms underlying RV's anticancer and chemopreventive effects are
      incompletely understood. Here we show that RV treatment inhibits the clonogenic
      growth of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner.
      Interestingly, the tumor-suppressive effect of low dose RV was not associated
      with any significant changes in the expression of cleaved PARP and activated
      caspase-3, suggesting that low dose RV treatment may suppress tumor cell growth
      via an apoptosis-independent mechanism. Subsequent studies reveal that low dose
      RV treatment induces a significant increase in senescence-associated beta
      galactosidase (SA-beta-gal) staining and elevated expression of p53 and p21 in
      NSCLC cells. Furthermore, we show that RV-induced suppression of lung cancer cell
      growth is associated with a decrease in the expression of EF1A. These results
      suggest that RV may exert its anticancer and chemopreventive effects through the
      induction of premature senescence. Mechanistically, RV-induced premature
      senescence correlates with increased DNA double strand breaks (DSBs) and reactive
      oxygen species (ROS) production in lung cancer cells. Inhibition of ROS
      production by N-acetylcysteine (NAC) attenuates RV-induced DNA DSBs and premature
      senescence. Furthermore, we show that RV treatment markedly induces NAPDH oxidase
      5 (Nox5) expression in both A549 and H460 cells, suggesting that RV may increase
      ROS generation in lung cancer cells through upregulating Nox5 expression.
      Together, these findings demonstrate that low dose RV treatment inhibits lung
      cancer cell growth via a previously unappreciated mechanism, namely the induction
      of premature senescence through ROS-mediated DNA damage.

PMID- 23533665
TI  - Emulsified phosphatidylserine, simple and effective peptide carrier for induction
      of potent epitope-specific T cell responses.
AB  - BACKGROUND: To induce potent epitope-specific T cell immunity by a peptide-based
      vaccine, epitope peptides must be delivered efficiently to antigen-presenting
      cells (APCs) in vivo. Therefore, selecting an appropriate peptide carrier is
      crucial for the development of an effective peptide vaccine. In this study, we
      explored new peptide carriers which show enhancement in cytotoxic T lymphocyte
      (CTL) induction capability. METHODOLOGY/PRINCIPAL FINDINGS: Data from an epitope
      specific in vivo CTL assay revealed that phosphatidylserine (PS) has a potent
      adjuvant effect among candidate materials tested. Further analyses showed that PS
      conjugated antigens were preferentially and efficiently captured by professional
      APCs, in particular, by CD11c(+)CD11b(+)MHCII(+) conventional dendritic cells
      (cDCs) compared to multilamellar liposome-conjugates or unconjugated antigens. In
      addition, PS demonstrated the stimulatory capacity of peptide-specific helper T
      cells in vivo. CONCLUSIONS/SIGNIFICANCE: This work indicates that PS is the
      easily preparable efficient carrier with a simple structure that delivers antigen
      to professional APCs effectively and induce both helper and cytotoxic T cell
      responses in vivo. Therefore, PS is a promising novel adjuvant for T cell
      inducing peptide vaccines.

PMID- 23533666
TI  - Dectin-1 regulates IL-10 production via a MSK1/2 and CREB dependent pathway and
      promotes the induction of regulatory macrophage markers.
AB  - In response to infection by fungal pathogens, the innate immune system recognises
      specific fungal pathogen associated molecular patterns (PAMPs) via pattern
      recognition receptors including the C-type lectin dectin-1 and members of the
      Toll Like Receptor (TLR) family. Stimulation of these receptors leads to the
      induction of both pro- and anti-inflammatory cytokines. The protein kinases MSK1
      and 2 are known to be important in limiting inflammatory cytokine production by
      macrophages in response to the TLR4 agonist LPS. In this study we show that MSKs
      are also activated in macrophages by the fungal derived ligand zymosan, as well
      as the dectin-1 specific agonists curdlan and depleted zymosan, via the ERK1/2
      and p38alpha MAPK pathways. Furthermore, we show that MSKs regulate dectin-1
      induced IL-10 production, and that this regulation is dependent on the ability of
      MSKs to phosphorylate the transcription factor CREB. IL-10 secreted in response
      to zymosan was able to promote STAT3 phosphorylation via an autocrine feedback
      loop. Consistent with the decreased IL-10 secretion in MSK1/2 knockout
      macrophages, these cells also had decreased STAT3 tyrosine phosphorylation
      relative to wild type controls after stimulation with zymosan. We further show
      that the reduction in IL-10 production in the MSK1/2 macrophages results in
      increased secretion of IL-12p40 in response to zymosan relative to wild type
      controls. The production of high levels of IL-10 but low levels of IL-12 has
      previously been associated with an M2b or 'regulatory' macrophage phenotype,
      which was initially described in macrophages stimulated with a combination of
      immune complexes and LPS. We found that zymosan, via dectin-1 activation, also
      leads to the expression of SphK1 and LIGHT, markers of a regulatory like
      phenotype in mouse macrophages. The expression of these makers was further
      reinforced by the high level of IL-10 secreted in response to zymosan
      stimulation.

PMID- 23533667
TI  - Secretome of peripheral blood mononuclear cells enhances wound healing.
AB  - Non-healing skin ulcers are often resistant to most common therapies. Treatment
      with growth factors has been demonstrated to improve closure of chronic wounds.
      Here we investigate whether lyophilized culture supernatant of freshly isolated
      peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC
      from healthy human individuals were prepared and cultured for 24 hours.
      Supernatants were collected, dialyzed and lyophilized (SEC(PBMC)). Six mm punch
      biopsy wounds were set on the backs of C57BL/6J-mice and SEC(PBMC) containing
      emulsion or controls were applied daily for three days. Morphology and neo
      angiogenesis were analyzed by H&E-staining and CD31 immuno-staining,
      respectively. In vitro effects on diverse skin cells were investigated by
      migration assays, cell cycle analysis, and tube formation assay. Signaling
      pathways were analyzed by Western blot analysis. Application of SEC(PBMC) on 6 mm
      punch biopsy wounds significantly enhanced wound closure. H&E staining of the
      wounds after 6 days revealed that wound healing was more advanced after
      application of SEC(PBMC) containing emulsion. Furthermore, there was a massive
      increase in CD31 positive cells, indicating enhanced neo-angiogenesis. In primary
      human fibroblasts (FB) and keratinocytes (KC) migration but not proliferation was
      induced. In endothelial cells (EC) SEC(PBMC) induced proliferation and tube
      formation in a matrigel-assay. In addition, SEC(PBMC) treatment of skin cells led
      to the induction of multiple signaling pathways involved in cell migration,
      proliferation and survival. In summary, we could show that emulsions containing
      the secretome of PBMC derived from healthy individuals accelerates wound healing
      in a mouse model and induce wound healing associated mechanisms in human primary
      skin cells. The formulation and use of such emulsions might therefore represent a
      possible novel option for the treatment of non-healing skin ulcers.

PMID- 23533668
TI  - Molecular and clinical studies in 138 Japanese patients with Silver-Russell
      syndrome.
AB  - BACKGROUND: Recent studies have revealed relative frequency and characteristic
      phenotype of two major causative factors for Silver-Russell syndrome (SRS), i.e.
      epimutation of the H19-differentially methylated region (DMR) and uniparental
      maternal disomy 7 (upd(7)mat), as well as multilocus methylation abnormalities
      and positive correlation between methylation index and body and placental sizes
      in H19-DMR epimutation. Furthermore, rare genomic alterations have been found in
      a few of patients with idiopathic SRS. Here, we performed molecular and clinical
      findings in 138 Japanese SRS patients, and examined these matters.
      METHODOLOGY/PRINCIPAL FINDINGS: We identified H19-DMR epimutation in cases 1-43
      (group 1), upd(7)mat in cases 44-52 (group 2), and neither H19-DMR epimutation
      nor upd(7)mat in cases 53-138 (group 3). Multilocus analysis revealed hyper- or
      hypomethylated DMRs in 2.4% of examined DMRs in group 1; in particular, an
      extremely hypomethylated ARHI-DMR was identified in case 13. Oligonucleotide
      array comparative genomic hybridization identified a ~3.86 Mb deletion at
      chromosome 17q24 in case 73. Epigenotype-phenotype analysis revealed that group 1
      had more reduced birth length and weight, more preserved birth occipitofrontal
      circumference (OFC), more frequent body asymmetry and brachydactyly, and less
      frequent speech delay than group 2. The degree of placental hypoplasia was
      similar between the two groups. In group 1, the methylation index for the H19-DMR
      was positively correlated with birth length and weight, present height and
      weight, and placental weight, but with neither birth nor present OFC.
      CONCLUSIONS/SIGNIFICANCE: The results are grossly consistent with the previously
      reported data, although the frequency of epimutations is lower in the Japanese
      SRS patients than in the Western European SRS patients. Furthermore, the results
      provide useful information regarding placental hypoplasia in SRS, clinical
      phenotypes of the hypomethylated ARHI-DMR, and underlying causative factors for
      idiopathic SRS.

PMID- 23533669
TI  - Flixweed is more competitive than winter wheat under ozone pollution: evidences
      from membrane lipid peroxidation, antioxidant enzymes and biomass.
AB  - To investigate the effects of ozone on winter wheat and flixweed under
      competition, two species were exposed to ambient, elevated and high [O3] for 30
      days, planted singly or in mixculture. Eco-physiological responses were examined
      at different [O3] and fumigating time. Ozone reduced the contents of chlorophyll,
      increased the accumulation of H2O2 and malondialdehyde in both wheat and
      flixweed. The effects of competition on chlorophyll content of wheat emerged at
      elevated and high [O3], while that of flixweed emerged only at high [O3]. The
      increase of H2O2 and malondialdehyde of flixweed was less than that of wheat
      under the same condition. Antioxidant enzyme activities of wheat and flixweed
      were seriously depressed by perennial and serious treatment using O3. However,
      short-term and moderate fumigation increased the activities of SOD and POD of
      wheat, and CAT of flixweed. The expression levels of antioxidant enzymes related
      genes provided explanation for these results. Furthermore, the increase of CAT
      expression of flixweed was much higher than that of SOD and POD expression of
      wheat. Ozone and competition resulted in significant reductions in biomass and
      grain yield in both winter wheat and flixweed. However, the negative effects on
      flixweed were less than wheat. Our results demonstrated that winter wheat is more
      sensitive to O3 and competition than flixweed, providing valuable data for
      further investigation on responses of winter wheat to ozone pollution, in
      particular combined with species competition.

PMID- 23533670
TI  - A highly selective and non-reaction based chemosensor for the detection of Hg2+
      ions using a luminescent iridium(III) complex.
AB  - We report herein a novel luminescent iridium(III) complex with two hydrophobic
      carbon chains as a non-reaction based chemosensor for the detection of Hg(2+)
      ions in aqueous solution (<0.002% of organic solvent attributed to the probe
      solution). Upon the addition of Hg(2+) ions, the emission intensity of the
      complex was significantly enhanced and this change could be monitored by the
      naked eye under UV irradiation. The iridium(III) complex shows high specificity
      for Hg(2+) ions over eighteen other cations. The system is capable of detecting
      micromolar levels of Hg(2+) ions, which is within the range of many chemical
      systems.

PMID- 23533671
TI  - Sarcopenia is independently associated with cardiovascular disease in older
      Korean adults: the Korea National Health and Nutrition Examination Survey
      (KNHANES) from 2009.
AB  - BACKGROUND: The association between sarcopenia and cardiovascular disease (CVD)
      in elderly people has not been adequately assessed. The aim of this study was to
      investigate whether CVD is more prevalent in subjects with sarcopenia independent
      of other well-established cardiovascular risk factors in older Korean adults.
      METHOD: This study utilized the representative Korean population data from the
      Korea National Health and Nutrition Examination Survey (KNHANES) which was
      conducted in 2009. Subjects older than 65 years of age with appendicular skeletal
      muscle mass (ASM) determined by dual energy X-ray absorptiometry were selected.
      The prevalence of sarcopenia in the older Korean adults was investigated, and it
      was determined whether sarcopenia is associated with CVD independent of other
      well-known risk factors. RESULTS: 1,578 subjects aged 65 years and older with the
      data for ASM were selected, and the overall prevalence of sarcopenia was 30.3% in
      men and 29.3% in women. Most of the risk factors for CVD such as age, waist
      circumference, body mass index, fasting plasma glucose and total cholesterol
      showed significant negative correlations with the ratio between appendicular
      skeletal muscle mass and body weight. Multiple logistic regression analysis
      demonstrated that sarcopenia was associated with CVD independent of other well
      documented risk factors, renal function and medications (OR, 1.768; 95% CI, 1.075
      2.909, P = 0.025). CONCLUSIONS: Sarcopenia was associated with the presence of
      CVD independent of other cardiovascular risk factors after adjusting renal
      function and medications.

PMID- 23533672
TI  - Rgs13 constrains early B cell responses and limits germinal center sizes.
AB  - Germinal centers (GCs) are microanatomic structures that develop in secondary
      lymphoid organs in response to antigenic stimulation. Within GCs B cells clonally
      expand and their immunoglobulin genes undergo class switch recombination and
      somatic hypermutation. Transcriptional profiling has identified a number of genes
      that are prominently expressed in GC B cells. Among them is Rgs13, which encodes
      an RGS protein with a dual function. Its canonical function is to accelerate the
      intrinsic GTPase activity of heterotrimeric G-protein alpha subunits at the
      plasma membrane, thereby limiting heterotrimeric G-protein signaling. A unique,
      non-canonical function of RGS13 occurs following translocation to the nucleus,
      where it represses CREB transcriptional activity. The functional role of RGS13 in
      GC B cells is unknown. To create a surrogate marker for Rgs13 expression and a
      loss of function mutation, we inserted a GFP coding region into the Rgs13 genomic
      locus. Following immunization GFP expression rapidly increased in activated B
      cells, persisted in GC B cells, but declined in newly generated memory B and
      plasma cells. Intravital microscopy of the inguinal lymph node (LN) of immunized
      mice revealed the rapid appearance of GFP(+) cells at LN interfollicular regions
      and along the T/B cell borders, and eventually within GCs. Analysis of WT, knock
      in, and mixed chimeric mice indicated that RGS13 constrains extra-follicular
      plasma cell generation, GC size, and GC B cell numbers. Analysis of select cell
      cycle and GC specific genes disclosed an aberrant gene expression profile in the
      Rgs13 deficient GC B cells. These results indicate that RGS13, likely acting at
      cell membranes and in nuclei, helps coordinate key decision points during the
      expansion and differentiation of naive B cells.

PMID- 23533673
TI  - Effect of salt stress on growth, Na+ accumulation and proline metabolism in
      potato (Solanum tuberosum) cultivars.
AB  - Potato (Solanum tuberosum) is a major crop world-wide and the productivity of
      currently used cultivars is strongly reduced at high soil salt levels. We
      compared the response of six potato cultivars to increased root NaCl
      concentrations. Cuttings were grown hydroponically and treated with 0 mM, 60 mM
      and 180 mM NaCl for one week. Growth reduction on salt was strongest for the
      cultivars Mozart and Mona Lisa with a severe senescence response at 180 mM NaCl
      and Mozart barely survived the treatment. The cultivars Desiree and Russett
      Burbank were more tolerant showing no senescence after salt treatment. A clear
      difference in Na(+) homeostasis was observed between sensitive and tolerant
      cultivars. The salt sensitive cultivar Mozart combined low Na(+) levels in root
      and stem with the highest leaf Na(+) concentration of all cultivars, resulting in
      a high Na(+) shoot distribution index (SDI) for Mozart as compared to Desiree.
      Overall, a positive correlation between salt tolerance and stem Na(+)
      accumulation was found and the SDI for Na(+) points to a role of stem Na(+)
      accumulation in tolerance. In stem tissue, Mozart accumulated more H2O2 and less
      proline compared to the tolerant cultivars. Analysis of the expression of proline
      biosynthesis genes in Mozart and Desiree showed a clear reduction in proline
      dehydrogenase (PDH) expression in both cultivars and an increase in pyrroline-5
      carboxylate synthetase 1 (P5CS1) gene expression in Desiree, but not in Mozart.
      Taken together, current day commercial cultivars show promising differences in
      salt tolerance and the results suggest that mechanisms of tolerance reside in the
      capacity of Na(+) accumulation in stem tissue, resulting in reduced Na(+)
      transport to the leaves.

PMID- 23533674
TI  - Transcriptional suppression, DNA methylation, and histone deacetylation of the
      regulator of G-protein signaling 10 (RGS10) gene in ovarian cancer cells.
AB  - RGS10 regulates ovarian cancer cell growth and survival, and RGS10 expression is
      suppressed in cell models of ovarian cancer chemoresistance. However, the
      mechanisms governing RGS10 expression in ovarian cancer are poorly understood.
      Here we report RGS10 suppression in primary ovarian cancer and CAOV-3 ovarian
      cancer cells compared to immortalized ovarian surface epithelial (IOSE) cells,
      and in A2780-AD chemoresistant cells compared to parental A2780 cells. RGS10-1
      and RGS10-2 transcripts are expressed in ovarian cancer cells, but only RGS10-1
      is suppressed in A2780-AD and CAOV-3 cells, and the RGS10-1 promoter is uniquely
      enriched in CpG dinucleotides. Pharmacological inhibition of DNA methyl
      transferases (DNMTs) increased RGS10 expression, suggesting potential regulation
      by DNA methylation. Bisulfite sequencing analysis identified a region of the
      RGS10-1 promoter with significantly enhanced DNA methylation in chemoresistant
      A2780-AD cells relative to parental A2780 cells. DNA methylation in CAOV-3 and
      IOSE cells was similar to A2780 cells. More marked differences were observed in
      histone acetylation of the RGS10-1 promoter. Acetylated histone H3 associated
      with the RGS10-1 promoter was significantly lower in A2780-AD cells compared to
      parental cells, with a corresponding increase in histone deacetylase (HDAC)
      enzyme association. Similarly, acetylated histone levels at the RGS10-1 promoter
      were markedly lower in CAOV-3 cells compared to IOSE cells, and HDAC1 binding was
      doubled in CAOV-3 cells. Finally, we show that pharmacological inhibition of DNMT
      or HDAC enzymes in chemoresistant A2780-AD cells increases RGS10 expression and
      enhances cisplatin toxicity. These data suggest that histone de-acetylation and
      DNA methylation correlate with RGS10 suppression and chemoresistance in ovarian
      cancer. Markers for loss of RGS10 expression may identify cancer cells with
      unique response to therapeutics.

PMID- 23533675
TI  - LKB1 mediates the development of conventional and innate T cells via AMP
      dependent kinase autonomous pathways.
AB  - The present study has examined the role of the serine/threonine kinase LKB1 in
      the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null
      DPs can respond to signals from the mature alpha/beta T-cell-antigen receptor and
      initiate positive selection. However, in the absence of LKB1, thymocytes fail to
      mature to conventional single positive cells causing severe lymphopenia in the
      peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive
      selection but important for the maturation of positively selected thymocytes.
      LKB1 also strikingly prevented the development of invariant Valpha14 NKT cells
      and innate TCR alphabeta gut lymphocytes. Previous studies with gain of function
      mutants have suggested that the role of LKB1 in T cell development is mediated by
      its substrate the AMP-activated protein kinase (AMPK). The present study now
      analyses the impact of AMPK deletion in DP thymocytes and shows that the role of
      LKB1 during the development of both conventional and innate T cells is mediated
      by AMPK-independent pathways.

PMID- 23533676
TI  - Effect of acute negative and positive energy balance on basal very-low density
      lipoprotein triglyceride metabolism in women.
AB  - BACKGROUND: Acute reduction in dietary energy intake reduces very low-density
      lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy
      surplus and obesity are associated with hypertriglyceridemia, the effect of acute
      overfeeding on VLDL-TG metabolism is not known. OBJECTIVE: The aim of the present
      study was to investigate the effects of acute negative and positive energy
      balance on VLDL-TG metabolism in healthy women. DESIGN: Ten healthy women (AGE:
      22.0+/-2.9 years, BMI: 21.2+/-1.3 kg/m(2)) underwent a stable isotopically
      labeled tracer infusion study to determine basal VLDL-TG kinetics after
      performing, in random order, three experimental trials on the previous day: i)
      isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy
      restriction of 2.89+/-0.42 MJ and iii) hypercaloric feeding with a dietary energy
      surplus of 2.91+/-0.32 MJ. The three diets had the same macronutrient
      composition. RESULTS: Fasting plasma VLDL-TG concentrations decreased by ~26%
      after hypocaloric feeding relative to the control trial (P = 0.037), owing to
      decreased hepatic VLDL-TG secretion rate (by 21%, P = 0.023) and increased VLDL
      TG plasma clearance rate (by ~12%, P = 0.016). Hypercaloric feeding increased
      plasma glucose concentration (P = 0.042) but had no effect on VLDL-TG
      concentration and kinetics compared to the control trial. CONCLUSION: Acute
      dietary energy deficit (~3MJ) leads to hypotriglyceridemia via a combination of
      decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other
      hand, acute dietary energy surplus (~3MJ) does not affect basal VLDL-TG
      metabolism but disrupts glucose homeostasis in healthy women.

PMID- 23533677
TI  - Functional morphology and sexual dimorphism of mouthparts of the short-faced
      scorpionfly Panorpodes kuandianensis (Mecoptera: Panorpodidae).
AB  - Mouthparts are closely associated with the feeding behavior and feeding habits of
      insects. The features of mouthparts frequently provide important traits for
      evolutionary biologists and systematists. The short-faced scorpionflies
      (Panorpodidae) are distinctly different from other families of Mecoptera by their
      extremely short rostrum. However, their feeding habits are largely unknown so
      far. In this study, the mouthpart morphology of Panorpodes kuandianensis Zhong et
      al., 2011 was investigated using scanning electron microscopy and histological
      techniques. The mandibulate mouthparts are situated at the tip of the short
      rostrum. The clypeus and labrum are short and lack distinct demarcation between
      them. The epipharynx is furnished with sublateral and median sensilla patches.
      The blade-shaped mandibles are sclerotized and symmetrical, bearing apical teeth
      and serrate inner margins. The maxilla and labium retain the structures of the
      typical pattern of biting insects. The hirsute galea, triangular pyramid-shaped
      lacinia, and labial palps are described in detail at ultrastructural level for
      the first time. Abundant sensilla are distributed on the surface of maxillary and
      labial palps. The sexual dimorphism of mouthparts is found in Panorpodes for the
      first time, mainly exhibiting on the emargination of the labrum and apical teeth
      of mandibles. Based on the features of mouthparts, the potential feeding strategy
      and feeding mechanism are briefly discussed in Panorpodes.

PMID- 23533678
TI  - The interleukin-17 receptor B subunit is essential for the Th2 response to
      Helicobacter pylori, but not for control of bacterial burden.
AB  - Helicobacter pylori infection leads to an inflammatory response in 100% of
      infected individuals. The inflammatory cells which are recruited to the gastric
      mucosa during infection produce several pro- and anti-inflammatory cytokines
      including several cytokines in the interleukin-17 family. The anti-inflammatory
      cytokine, interleukin 25 (IL-25, also known as IL-17E), signals through a
      receptor, which is a heterotrimeric receptor comprised of two IL-17 receptor A
      subunits and an IL-17 receptor B subunit. Previous studies in our laboratory
      demonstrated that IL-17RA is required to control infection with Helicobacter
      pylori in the mouse model. Moreover, the absence of IL-17 receptor A leads to a
      significant B cell infiltrate and a remarkable increase in lymphoid follicle
      formation in response to infection compared to infection in wild-type mice. We
      hypothesized that IL-25, which requires both IL-17 receptor A and IL-17 receptor
      B for signaling, may play a role in control of inflammation in the mouse model of
      Helicobacter pylori infection. IL-17 receptor B deficient mice, IL-17 receptor A
      deficient mice and wild-type mice were infected with Helicobacter pylori (strains
      SS1 and PMSS1). At several time points H. pylori-infected mice were sacrificed to
      investigate their ability to control infection and inflammation. Moreover, the
      effects of IL-17 receptor B deficiency on T helper cytokine expression and H.
      pylori- specific serum antibody responses were measured. IL-17 receptor B-/- mice
      (unlike IL-17 receptor A-/- mice) exhibited similar or modest changes in gastric
      colonization, inflammation, and Th1 and Th17 helper cytokine responses to wild
      type mice infected with Helicobacter pylori. However, H. pylori-infected IL-17
      receptor B-/- mice have reduced expression of IL-4 and lower serum IgG1 and IgG2a
      levels compared to infected IL-17 receptor A-/- and wild-type mice. These data
      indicate that signaling through the IL-17 receptor B subunit is not necessary for
      control of Helicobacter pylori in our model.

PMID- 23533679
TI  - Selection affects genes involved in replication during long-term evolution in
      experimental populations of the bacteriophage phiX174.
AB  - Observing organisms that evolve in response to strong selection over very short
      time scales allows the determination of the molecular mechanisms underlying
      adaptation. Although dissecting these molecular mechanisms is expensive and time
      consuming, general patterns can be detected from repeated experiments,
      illuminating the biological processes involved in evolutionary adaptation. The
      bacteriophage phiX174 was grown for 50 days in replicate chemostats under two
      culture conditions: Escherichia coli C as host growing at 37 degrees C and
      Salmonella typhimurium as host growing at 43.5 degrees C. After 50 days, greater
      than 20 substitutions per chemostat had risen to detectable levels. Of the 97
      substitutions, four occurred in all four chemostats, five arose in both culture
      conditions, eight arose in only the high temperature S. typhimurium chemostats,
      and seven arose only in the E. coli chemostats. The remaining substitutions were
      detected only in a single chemostat, however, almost half of these have been seen
      in other similar experiments. Our findings support previous studies that host
      recognition and capsid stability are two biological processes that are modified
      during adaptation to novel hosts and high temperature. Based upon the
      substitutions shared across both environments, it is apparent that genome
      replication and packaging are also affected during adaptation to the chemostat
      environment, rather than to temperature or host per se. This environment is
      characterized by a large number of phage and very few hosts, leading to
      competition among phage within the host. We conclude from these results that
      adaptation to a high density environment selects for changes in genome
      replication at both protein and DNA sequence levels.

PMID- 23533680
TI  - Hsp21 potentiates antifungal drug tolerance in Candida albicans.
AB  - Systemic infections of humans with the fungal pathogen Candida albicans are
      associated with a high mortality rate. Currently, efficient treatment of these
      infections is hampered by the relatively low number of available antifungal
      drugs. We recently identified the small heat shock protein Hsp21 in C. albicans
      and demonstrated its fundamental role for environmental stress adaptation and
      fungal virulence. Hsp21 was found in several pathogenic Candida species but not
      in humans. This prompted us to investigate the effects of a broad range of
      different antifungal drugs on an Hsp21-null C. albicans mutant strain. Our
      results indicate that combinatorial therapy targeting Hsp21, together with
      specific antifungal drug targets, has strong synergistic potential. In addition,
      we demonstrate that Hsp21 is required for tolerance to ethanol-induced stress and
      induction of filamentation in response to pharmacological inhibition of Hsp90.
      These findings might pave the way for the development of new treatment strategies
      against Candida infections.

PMID- 23533681
TI  - Fv1 restriction and retrovirus vaccine immunity in Apobec3-deficient 129P2 mice.
AB  - Understanding the host genetics of the immune response in retrovirus infection
      models could provide insights for basic HIV vaccine discovery. In Friend
      retrovirus (FV) infection of mice, Fv1 differentially inhibits N-tropic versus B
      tropic FV infection by mediating a capsid-dependent post-entry block, Fv2
      susceptibility governs splenomegaly induction, and Rfv3 resistance primes a
      stronger neutralizing antibody response due to more potent Apobec3 activity.
      Apobec3 polymorphisms in inbred mouse strains correlate with Rfv3 resistance and
      susceptibility, with one unresolved exception. The 129/OlaHsd (129P2) mouse
      strain is Fv2 and Rfv3 susceptible based on genotyping, but infection of 129P2
      mice with B-tropic FV resulted in strong neutralizing antibody responses and no
      splenomegaly. Here we confirm that 129P2 mice are Fv1(nr/nr), explaining its
      resistance to B-tropic FV. Infection of 129P2 mice with NB-tropic FV, which can
      efficiently infect mice independent of Fv1 genotype, resulted in severe
      splenomegaly, high levels of viremia and weak neutralizing antibody responses
      regardless of Apobec3 status. Notably, high-dose B-tropic FV infection of 129P2
      Apobec3-deficient mice induced significant adaptive immune responses and
      conferred high levels of protection following challenge with pathogenic NB-tropic
      FV. This immunological protection complemented previous studies that N-tropic FV
      can act as a live-attenuated vaccine in Fv1 (b/b) mice. Altogether, the results
      obtained in 129P2 mice strengthen the conclusion that Rfv3 is encoded by Apobec3,
      and highlight Fv1 incompatibility as a retroviral vaccine paradigm in mice. Due
      to its susceptibility to disease that allows for pathogenic challenge studies, B
      tropic FV infection of 129P2 mice may be a useful model to study the
      immunological pathways induced by retroviral capsid restriction.

PMID- 23533682
TI  - Cortical depth dependent functional responses in humans at 7T: improved
      specificity with 3D GRASE.
AB  - Ultra high fields (7T and above) allow functional imaging with high contrast-to
      noise ratios and improved spatial resolution. This, along with improved hardware
      and imaging techniques, allow investigating columnar and laminar functional
      responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer
      specific responses have been recorded from human (and animal) primary visual
      areas. However, their increased sensitivity to large surface veins potentially
      clouds detecting and interpreting layer specific responses. Conversely, spin-echo
      (SE) (T2 weighted) sequences are less sensitive to large veins and have been used
      to map cortical columns in humans. T2 weighted 3D GRASE with inner volume
      selection provides high isotropic resolution over extended volumes, overcoming
      some of the many technical limitations of conventional 2D SE-EPI, whereby making
      layer specific investigations feasible. Further, the demonstration of columnar
      level specificity with 3D GRASE, despite contributions from both stimulated
      echoes and conventional T2 contrast, has made it an attractive alternative over
      2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D
      GRASE functional responses in human V1 and hMT by comparing it to GE responses.
      In doing so we demonstrate that 3D GRASE is less sensitive to contributions from
      large veins in superficial layers, while showing increased specificity
      (functional tuning) throughout the cortex compared to GE.

PMID- 23533683
TI  - Blocking type I interferon signaling rescues lymphocytes from oxidative stress,
      exhaustion, and apoptosis in a streptozotocin-induced mouse model of type I
      diabetes.
AB  - Elevated levels of type I interferon (IFN) during type 1 diabetes mellitus (T1D)
      are associated with a defective immune response. In the present study, we
      investigated whether blocking type I IFN signaling during streptozotocin- (STZ-)
      induced T1D in mice improves lymphocyte proliferation and escape from continuous
      apoptosis. Three groups of mice were examined: diabetic mice, type I IFN
      signaling-incompetent diabetic mice, and control nondiabetic mice. We first found
      that diabetes induction was accompanied by an elevation in the plasma levels of
      reactive oxygen species (ROS), hydroperoxide, malondialdehyde (MDN), and the
      proinflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and CXCL10. Blocking type
      1 IFN signaling in diabetic mice significantly decreased the levels of oxidative
      stress and proinflammatory cytokines. In addition, lymphocytes from diabetic mice
      exhibited a marked reduction in their proliferative capacity, increased
      apoptosis, upregulation of the exhaustion marker PD-1, and aberrant
      phosphorylation of STAT1, STAT2, AKT and I kappa B- alpha. Interestingly,
      following the blocking of type I IFN signaling in diabetic mice, the lymphocytes
      exhibited restored proliferative capacity, decreased apoptosis, normal expression
      of PD-1, and normal phosphorylation of STAT1, STAT2, AKT and I kappa B- alpha.
      Our data suggest that elevated levels of type I IFN during T1D trigger lymphocyte
      exhaustion and a defective lymphocyte-medicated immune response.

PMID- 23533684
TI  - Dual phases of respiration chain defect-augmented mROS-mediated mCa 2+ stress
      during oxidative insult in normal and rho 0 RBA1 astrocytes.
AB  - Mitochondrial respiratory chain (RC) deficits, resulting in augmented
      mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes.
      However, mtDNA-depleted cells (rho (0)) lacking RC have been reported to be
      either sensitive or resistant to apoptosis. In this study, we sought to determine
      the effects of RC-enhanced mitochondrial stress following oxidative insult. Using
      noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the
      ability to resist oxidative stress and levels of mROS formation and mitochondrial
      calcium (mCa(2+)) were compared between two different astrocyte cell lines,
      control and rho (0) astrocytes, over time upon oxidative stress. Our results
      showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150
      and 130 minutes in RBA-1 and rho (0) astrocytes, respectively. In contrast to RBA
      1, 30 minutes after 20 mM H2O2 exposure, rho (0) astrocytes formed marked plasma
      membrane blebs, lost the ability to retain Mito-R, and showed condensation of
      nuclei. Importantly, H2O2-induced ROS and accompanied mCa(2+) elevation in
      control showed higher levels than rho (0) at early time point but vice versa at
      late time point. Our findings underscore dual phase of RC-defective cells
      harboring less mitochondrial stress due to low RC activity during short-term
      oxidative stress but augmented mROS-mediated mCa(2+) stress during severe
      oxidative insult.

PMID- 23533686
TI  - Oxidative stress is related to the deleterious effects of heme oxygenase-1 in an
      in vivo neuroinflammatory rat model.
AB  - Heme oxygenase-1 (HO-1) induction is associated with beneficial or deleterious
      effects depending on the experimental conditions adopted and the
      neurodegenerative rodent models used. The present study aimed first to evaluate
      the effects of cerebral HO-1 induction in an in vivo rat model of
      neuroinflammation by intrastriatal injection of quinolinic acid (QA) and secondly
      to explore the role played by reactive oxygen species (ROS) and free iron
      (Fe(2+)) derived from heme catabolism promoted by HO-1. Chronic I.P. treatment
      with the HO-1 inductor and substrate hemin was responsible for a significant dose
      related increase of cerebral HO-1 production. Brain tissue loss, microglial
      activation, and neuronal death were significantly higher in rats receiving QA
      plus hemin (H-QA) versus QA and controls. Significant increase of ROS production
      in H-QA rat brain was inhibited by the specific HO-1 inhibitor ZnPP which
      supports the idea that ROS level augmentation in hemin-treated animals is a
      direct consequence of HO-1 induction. The cerebral tissue loss and ROS level in
      hemin-treated rats receiving the iron chelator deferoxamine were significantly
      decreased, demonstrating the involvement of Fe(2+)in brain ROS production.
      Therefore, the deleterious effects of HO-1 expression in this in vivo
      neuroinflammatory model were linked to a hyperproduction of ROS, itself promoted
      by free iron liberation.

PMID- 23533685
TI  - Obstructive sleep apnea, oxidative stress and cardiovascular disease: lessons
      from animal studies.
AB  - Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular
      (CV) diseases such as arterial hypertension, heart failure, and stroke. Based on
      human research, sympathetic activation, inflammation, and oxidative stress are
      thought to play major roles in the pathophysiology of OSA-related CV diseases.
      Animal models of OSA have shown that endothelial dysfunction, vascular
      remodelling, and systemic and pulmonary arterial hypertension as well as heart
      failure can develop in response to chronic intermittent hypoxia (CIH). The
      available animal data are clearly in favour of oxidative stress playing a key
      role in the development of all of these CV manifestations of OSA. Presumably, the
      oxidative stress is due to an activation of NADPH oxidase and other free oxygen
      radicals producing enzymes within the CV system as evidenced by data from
      knockout mice and pharmacological interventions. It is hoped that animal models
      of OSA-related CV disease will continue to contribute to a deeper understanding
      of their underlying pathophysiology and will foster the way for the development
      of cardioprotective treatment options other than conventional CPAP therapy.

PMID- 23533687
TI  - Triggers and effectors of oxidative stress at blood-brain barrier level:
      relevance for brain ageing and neurodegeneration.
AB  - As fundamental research advances, it is becoming increasingly clear that a
      clinically expressed disease implies a mixture of intertwining molecular
      disturbances. Oxidative stress is one of such pathogenic pathways involved in
      virtually all central nervous system pathologies, infectious, inflammatory, or
      degenerative in nature. Since brain homeostasis largely depends on integrity of
      blood-brain barrier (BBB), many studies focused lately on BBB alteration in a
      wide spectrum of brain diseases. The proper two-way molecular transfer through
      BBB depends on several factors, including the functional status of its tight
      junction (TJ) complexes of proteins sealing neighbour endothelial cells. Although
      there is abundant experimental work showing that oxidative stress associates BBB
      permeability alteration, less is known about its implications, at molecular
      level, in TJ protein expression or TJ-related cell signalling. In this paper,
      oxidative stress is presented as a common pathway for different brain pathogenic
      mechanisms which lead to BBB dysregulation. We revise here oxidative-induced
      molecular mechanisms of BBB disruption and TJ protein expression alteration, in
      relation to ageing and neurodegeneration.

PMID- 23533688
TI  - Preventive and therapeutic effects of MG132 by activating Nrf2-ARE signaling
      pathway on oxidative stress-induced cardiovascular and renal injury.
AB  - So far, cardiovascular and renal diseases have brought us not only huge economic
      burden but also serious society problems. Since effective therapeutic strategies
      are still limited, to find new methods for the prevention or therapy of these
      diseases is important. Oxidative stress has been found to play a critical role in
      the initiation and progression of cardiovascular and renal diseases. In addition,
      activation of nuclear-factor-E2-related-factor-2- (Nrf2-) antioxidant-responsive
      element (ARE) signaling pathway protects cells and tissues from oxidative damage.
      As a proteasomal inhibitor, MG132 was reported to activate Nrf2 expression and
      function, which was accompanied with significant preventive and/or therapeutic
      effect on cardiovascular and renal diseases under most conditions; therefore,
      MG132 seems to be a potentially effective drug to be used in the prevention of
      oxidative damage. In this paper, we will summarize the information available
      regarding the effect of MG132 on oxidative stress-induced cardiovascular and
      renal damage, especially through Nrf2-ARE signaling pathway.

PMID- 23533689
TI  - Nordihydroguaiaretic acid attenuates the oxidative stress-induced decrease of
      CD33 expression in human monocytes.
AB  - Nordihydroguaiaretic acid (NDGA) is a natural lignan with recognized antioxidant
      and beneficial properties that is isolated from Larrea tridentata. In this study,
      we evaluated the effect of NDGA on the downregulation of oxidant stress-induced
      CD33 in human monocytes (MNs). Oxidative stress was induced by iodoacetate (IAA)
      or hydrogen peroxide (H(2)O(2)) and was evaluated using reactive oxygen species
      (ROS) production, and cell viability. NDGA attenuates toxicity, ROS production
      and the oxidative stress-induced decrease of CD33 expression secondary to IAA or
      H(2)O(2) in human MNs. It was also shown that NDGA (20  MU M) attenuates cell
      death in the THP-1 cell line that is caused by treatment with either IAA or
      H(2)O(2). These results suggest that NDGA has a protective effect on CD33
      expression, which is associated with its antioxidant activity in human MNs.

PMID- 23533691
TI  - Effects of open versus laparoscopic nephrectomy techniques on oxidative stress
      markers in patients with renal cell carcinoma.
AB  - The aim of the study was to determine the concentration of lipid peroxidation
      products, the activity of selected antioxidant and lysosomal enzymes, and
      protease inhibitor in patients with renal cell carcinoma who underwent radical
      nephrectomy. The studied group included 44 patients: 21 of them underwent open
      surgery, while 23 underwent laparoscopy. Blood samples were collected three
      times: before treatment and 12 hours and five days after nephrectomy. In blood of
      participants, the concentration of thiobarbituric acid reactive substances
      (TBARS), the activity of catalase (CAT), superoxide dismutase (SOD) and
      glutathione peroxidase (GPx), and the activity of acid phosphatase (AcP),
      arylsulfatase (ASA), cathepsin D (CTSD), and alpha 1-antitrypsin (AAT) were
      assayed. No statistically significant differences in investigated parameters were
      found between studied groups. Moreover, TBARS concentration and CAT, SOD, and GPx
      activity were not altered in the course of both types of surgery. Five days after
      both open and laparoscopic nephrectomy techniques, AAT activity was higher than
      its activity 12 hours after the procedure. The obtained results suggest that
      laparoscopy may be used for nephrectomy as effectively as open surgery without
      creating greater oxidative stress. Reduced period of convalescence at patients
      treated with laparoscopy may be due to less severe response of acute-phase
      proteins.

PMID- 23533692
TI  - Sweet chestnut (Castanea sativa Mill.) bark extract: cardiovascular activity and
      myocyte protection against oxidative damage.
AB  - This work was aimed at evaluating the cardioprotective effects of Castanea sativa
      Mill. (CSM) bark extract characterized in its phenolic composition by HPLC-DAD-MS
      analysis. The study was performed using primary cultures of neonatal rat
      cardiomyocytes to investigate the antioxidant and cytoprotective effects of CSM
      bark extract and isolated guinea pig left and right atria, left papillary muscle,
      and aorta to evaluate its direct effect on cholinergic and adrenergic response.
      In cultured cardiomyocytes the CSM bark extract reduced intracellular reactive
      oxygen species formation and improved cell viability following oxidative stress
      in dose-dependent manner. Moreover, the extract decreased the contraction induced
      by noradrenaline (1  MU M) in guinea pig aortic strips and induced transient
      negative chronotropic and positive inotropic effects without involvement of
      cholinergic or adrenergic receptors in the guinea pig atria. Our results indicate
      that CSM bark extract exhibits antioxidant activity and might induce
      cardioprotective effect.

PMID- 23533690
TI  - Redox regulation in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results
      from the death of upper and lower motor neurons. Due to a lack of effective
      treatment, it is imperative to understand the underlying mechanisms and processes
      involved in disease progression. Regulations in cellular reduction/oxidation
      (redox) processes are being increasingly implicated in disease. Here we discuss
      the possible involvement of redox dysregulation in the pathophysiology of ALS,
      either as a cause of cellular abnormalities or a consequence. We focus on its
      possible role in oxidative stress, protein misfolding, glutamate excitotoxicity,
      lipid peroxidation and cholesterol esterification, mitochondrial dysfunction,
      impaired axonal transport and neurofilament aggregation, autophagic stress, and
      endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein
      disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is
      essential for normal protein folding by oxidation and reduction of disulphide
      bonds, and hence any disruption to this process may have consequences for motor
      neurons. Addressing the mechanism underlying redox regulation and dysregulation
      may therefore help to unravel the molecular mechanism involved in ALS.

PMID- 23533693
TI  - The effect of alpha-lipoic acid on mitochondrial superoxide and glucocorticoid
      induced hypertension.
AB  - AIMS: To examine the effect of alpha-lipoic acid, an antioxidant with
      mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone-
      (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any
      antihypertensive effect is mediated via mitochondrial superoxide inhibition.
      METHODS: In a prevention study, rats received ground food or alpha-lipoic-acid
      laced food (10 mg/rat/day) for 15 nights. Saline, adrenocorticotrophic hormone
      (ACTH, 0.2 mg/kg/day), or dexamethasone (DEX, 10  MU g/rat/day) was injected
      subcutaneously from day 5 to day 11. In a reversal study, rats received alpha
      lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff
      systolic blood pressure (SBP) was measured second daily. Kidney mitochondrial
      superoxide was examined using (MitoSOX) Red (MitoSOX) via flow cytometry.
      RESULTS: SBP was increased by ACTH (P < 0.0005) and DEX (P < 0.0005). Alpha
      lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was
      increased by ACTH (P' < 0.005) but not by DEX. Alpha-lipoic partially prevented
      ACTH-HT (P' < 0.0005) and fully prevented DEX-HT (P' < 0.0005) but failed to
      reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH
      hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day) did not decrease
      SBP further but raised MitoSOX signal (P < 0.001), suggesting prooxidant
      activity. CONCLUSION: Glucocorticoid-induced hypertension in rats is prevented by
      alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.

PMID- 23533694
TI  - Pituitary adenoma nitroproteomics: current status and perspectives.
AB  - Oxidative stress is extensively associated with tumorigenesis. A series of
      studies on stable tyrosine nitration as a marker of oxidative damage were
      performed in human pituitary and adenoma. This paper reviews published research
      on the mass spectrometry characteristics of nitropeptides and nitroproteomics of
      pituitary controls and adenomas. The methodology used for nitroproteomics, the
      current status of human pituitary nitroproteomics studies, and the future
      perspectives are reviewed. Enrichment of those low-abundance endogenous
      nitroproteins from human tissues or body fluid samples is the first important
      step for nitroproteomics studies. Mass spectrometry is the essential approach to
      determine the amino acid sequence and locate the nitrotyrosine sites.
      Bioinformatics analyses, including protein domain and motif analyses, are needed
      to locate the nitrotyrosine site within the corresponding protein domains/motifs.
      Systems biology techniques, including pathway analysis, are necessary to discover
      signaling pathway networks involving nitroproteins from the systematically global
      point of view. Future quantitative nitroproteomics will discover pituitary
      adenoma-specific nitroprotein(s). Structural biology techniques such as X-ray
      crystallography analysis will solidly clarify the effects of tyrosine nitration
      on structure and functions of a protein. Those studies will eventually address
      the mechanisms and biological functions of tyrosine nitration in pituitary
      tumorigenesis and will discover nitroprotein biomarkers for pituitary adenomas
      and targets for drug design for pituitary adenoma therapy.

PMID- 23533695
TI  - Function and characteristics of PINK1 in mitochondria.
AB  - Mutations in phosphatase and tensin homologue-induced kinase 1 (PINK1) cause
      recessively inherited Parkinson's disease, a neurodegenerative disorder linked to
      mitochondrial dysfunction. Studies support the notion of neuroprotective roles
      for the PINK1, as it protects cells from damage-mediated mitochondrial
      dysfunction, oxidative stress, and cell apoptosis. PARL is a mitochondrial
      resident rhomboid serine protease, and it has been reported to mediate the
      cleavage of the PINK1. Interestingly, impaired mitophagy, an important autophagic
      quality control mechanism that clears the cells of damaged mitochondria, may also
      be an underlying mechanism of disease pathogenesis in patients for Parkinson's
      disease with the PARL mutations. Functional studies have revealed that PINK1
      recruits Parkin to mitochondria to initiate the mitophagy. PINK1 is
      posttranslationally processed, whose level is definitely regulated in healthy
      steady state of mitochondria. As a consequence, PINK1 plays a pivotal role in
      mitochondrial healthy homeostasis.

PMID- 23533697
TI  - The triggering receptor expressed on myeloid cells 2: "TREM-ming" the
      inflammatory component associated with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder
      characterized by a progressive loss of memory and cognitive skills. Although much
      attention has been devoted concerning the contribution of the microscopic
      lesions, senile plaques, and neurofibrillary tangles to the disease process,
      inflammation has long been suspected to play a major role in the etiology of AD.
      Recently, a novel variant in the gene encoding the triggering receptor expressed
      on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight
      back onto inflammation as a major contributing factor in AD. Variants in TREM2
      triple one's risk of developing late-onset AD. TREM2 is expressed on microglial
      cells, the resident macrophages in the CNS, and functions to stimulate
      phagocytosis on one hand and to suppress cytokine production and inflammation on
      the other hand. The purpose of this paper is to discuss these recent developments
      including the potential role that TREM2 normally plays and how loss of function
      may contribute to AD pathogenesis by enhancing oxidative stress and inflammation
      within the CNS. In this context, an overview of the pathways linking beta
      amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will
      be discussed.

PMID- 23533698
TI  - Nrf2 is crucial to graft survival in a rodent model of heart transplantation.
AB  - Currently, the sole treatment option for patients with heart failure is
      transplantation. The battle of prolonging graft survival and modulating innate
      and adaptive immune responses is still being waged in the clinic and in research
      labs. The transcription factor Nrf2 controls major cell survival pathways and is
      central to moderating inflammation and immune responses. In this study the effect
      of Nrf2 levels in host recipient C57BL/6 mice on Balb/c allogeneic graft survival
      was examined. Importantly, Nrf2(-/-) recipient mice could not support the graft
      for longer than 7.5 days on average, whereas activation of Nrf2 by sulforaphane
      in Nrf2(+/+) hosts prolonged graft survival to 13 days. Several immune cells in
      the spleen of recipient mice were unchanged; however, CD11b(+) macrophages were
      significantly increased in Nrf2(-/-) mice. In addition, IL-17 mRNA levels were
      elevated in grafts transplanted into Nrf2(-/-) mice. Although Nrf2 appears to
      play a crucial role in graft survival, the exact mechanism is yet to be fully
      understood.

PMID- 23533696
TI  - Oxidized extracellular DNA as a stress signal in human cells.
AB  - The term "cell-free DNA" (cfDNA) was recently coined for DNA fragments from
      plasma/serum, while DNA present in in vitro cell culture media is known as
      extracellular DNA (ecDNA). Under oxidative stress conditions, the levels of
      oxidative modification of cellular DNA and the rate of cell death increase. Dying
      cells release their damaged DNA, thus, contributing oxidized DNA fragments to the
      pool of cfDNA/ecDNA. Oxidized cell-free DNA could serve as a stress signal that
      promotes irradiation-induced bystander effect. Evidence points to TLR9 as a
      possible candidate for oxidized DNA sensor. An exposure to oxidized ecDNA
      stimulates a synthesis of reactive oxygen species (ROS) that evokes an adaptive
      response that includes transposition of the homologous loci within the nucleus,
      polymerization and the formation of the stress fibers of the actin, as well as
      activation of the ribosomal gene expression, and nuclear translocation of NF-E2
      related factor-2 (NRF2) that, in turn, mediates induction of phase II detoxifying
      and antioxidant enzymes. In conclusion, the oxidized DNA is a stress signal
      released in response to oxidative stress in the cultured cells and, possibly, in
      the human body; in particular, it might contribute to systemic abscopal effects
      of localized irradiation treatments.

PMID- 23533699
TI  - Review of Clinical Features, Microbiological Spectrum, and Treatment Outcomes of
      Endogenous Endophthalmitis over an 8-Year Period.
AB  - Purpose. To evaluate the clinical features, microbiological spectrum, and
      treatment outcomes of endogenous endophthalmitis. Methods. Retrospective review
      of consecutive cases with infective endogenous endophthalmitis presenting from
      2000 to 2007. The main outcome measure was the visual outcome at the latest
      follow-up visit. Other outcome measures included microbiological investigations,
      anatomical and clinical outcomes. Results. 22 eyes of 21 patients were included,
      and the mean follow-up duration was 2.7 years. Eyes with fungal endogenous
      endophthalmitis were more likely to have visual acuity of finger counting or
      better at presentation compared with those with bacterial endogenous
      endophthalmitis (odds ratio = 15.0, P = 0.013). Gram-negative microorganisms
      accounted for 50% of infections, while fungal and gram-positive organisms
      accounted for 27.3% and 22.7%, respectively. Despite treatment, the visual
      outcome was poor in general as 10 (45.5%) eyes had no light perception at the
      latest follow-up visit and 6 (27.3%) eyes required enucleation or evisceration.
      Contrary to previous studies, fungal endogenous endophthalmitis did not appear to
      have better visual outcome compared with bacterial endogenous endophthalmitis.
      Conclusion. Gram-negative microorganisms were the main causative pathogens of
      endogenous endophthalmitis in Hong Kong. The visual prognosis of endogenous
      endophthalmitis is generally poor as almost 50% of eyes were blind despite
      treatment.

PMID- 23533701
TI  - Comparison of wide conjunctival flap and conjunctival autografting techniques in
      pterygium surgery.
AB  - Pterygium is an abnormal fibrovascular tissue extending on the cornea which is a
      degenerative and hyperplastic disorder. A stromal overgrowth of fibroblast and
      blood vessels is accompanied by an inflammatory cell infiltrate and abnormal
      extracellular matrix accumulation. The surgical excision is the main treatment
      method of pterygium, but recurrence is the most common postoperative
      complication. In the present study, we aimed to compare the wide conjunctival
      flap and the conjunctival autografting techniques in pterygium surgery according
      to time of operation, safety, and effectiveness. Results showed that the effect
      of wide conjunctival flap techniques on primary pterygium surgery was found close
      to the conjunctival autograft techniques. In addition, the flap technique has a
      shorter surgical time, the surgery does not require extreme experience, feeding
      of the flap is provided with own vessels since the vascular structure is
      protected on the upper temporal conjunctival area, reverse placement of the flap
      is not seen, it needs fewer sutures, so that suture disturbances may reduce, and
      it is less traumatic than autograft technique during conjunctival transport.
      Therefore, this technique may be preferred in suitable cases.

PMID- 23533702
TI  - Aqueous Concentrations of Vascular Endothelial Growth Factor in Eyes with High
      Myopia with and without Choroidal Neovascularization.
AB  - Purpose. To investigate aqueous concentrations of vascular endothelial growth
      factor (VEGF) in eyes with myopic choroidal neovascularization (CNV). Methods.
      Aqueous samples were collected, and VEGF concentrations were measured by enzyme
      linked immunosorbent assay in 16 eyes (16 patients) with active myopic CNV, 23
      eyes (16 patients) with high myopia without myopic CNV, and 8 control eyes (7
      patients). Differences in the concentrations of VEGF in each group were compared.
      Results. The estimated mean VEGF concentrations were significantly lower in eyes
      with myopic CNV (82.0 pg/mL) (P = 0.016 ) and with high myopia without myopic CNV
      (58.9 pg/mL) (P < 0.001) compared with controls (116.6 pg/mL). The estimated mean
      VEGF concentration was significantly (P < 0.05) higher in eyes with myopic CNV
      than in those without myopic CNV in highly myopic eyes. In eyes with high myopia
      with and without CNV, the VEGF concentration was significantly (stepwise
      regression analysis, R = 0.325, P = 0.044) associated with the presence of myopic
      CNV but not with age, axial length, or intraocular pressure. Conclusion.
      Increased levels of VEGF may play a role in the pathogenesis of CNV in highly
      myopic eyes.

PMID- 23533703
TI  - Visual performance in patients with neovascular age-related macular degeneration
      undergoing treatment with intravitreal ranibizumab.
AB  - Purpose. To assess visual function and its response to serial intravitreal
      ranibizumab (Lucentis, Genentech) in patients with neovascular age-related
      macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv
      AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing
      intravitreal injections of ranibizumab, were enrolled into this prospective
      study. Visual function was assessed using a range of psychophysical tests, while
      mean foveal thickness (MFT) was determined by optical coherence tomography (OCT).
      Results. Group mean (+/-sd) MFT reduced significantly from baseline (233 (+/-59))
      to exit (205 (+/-40)) (P = 0.001). CDVA exhibited no change between baseline and
      exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did
      exhibit statistically significant improvements (P < 0.05 for all) included
      reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS),
      mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity
      (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal
      ranibizumab injections exhibit improvements in many parameters of visual
      function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not
      only be considered in the design of studies investigating nv-AMD, but also in
      treatment and retreatment strategies for patients with the condition.

PMID- 23533704
TI  - Clinical applications of high resolution in-vivo retinal imaging.

PMID- 23533700
TI  - Ocular surface development and gene expression.
AB  - The ocular surface-a continuous epithelial surface with regional specializations
      including the surface and glandular epithelia of the cornea, conjunctiva, and
      lacrimal and meibomian glands connected by the overlying tear film-plays a
      central role in vision. Molecular and cellular events involved in embryonic
      development, postnatal maturation, and maintenance of the ocular surface are
      precisely regulated at the level of gene expression by a well-coordinated network
      of transcription factors. A thorough appreciation of the biological
      characteristics of the ocular surface in terms of its gene expression profiles
      and their regulation provides us with a valuable insight into the pathophysiology
      of various blinding disorders that disrupt the normal development, maturation,
      and/or maintenance of the ocular surface. This paper summarizes the current
      status of our knowledge related to the ocular surface development and gene
      expression and the contribution of different transcription factors to this
      process.

PMID- 23533705
TI  - In vivo comparison of 23- and 25-gauge sutureless vitrectomy incision
      architecture using spectral domain optical coherence tomography.
AB  - Purpose. To investigate the in vivo incision architecture using spectral domain
      optical coherence tomography (SD-OCT) in 23-gauge and 25-gauge transconjunctival
      sutureless pars plana vitrectomy (TSPPV). Methods. A prospective observational
      study of 22 eyes of 22 patients that underwent three-port 25-gauge (10 eyes) or
      23-gauge (12 eyes) TSPPV was performed. The three sclerotomies sites in each eye
      were analyzed by Corneal Adapter Model (CAM) RTVue SD-OCT (Optovue Inc., Fremont,
      CA, USA) with wound cross-section images (longitudinal and transversal) on days
      1, 7, and 30 postoperatively. Transversal and longitudinal length, location,
      angle between the conjunctival surface tangent and the incision plane, and
      architecture deformations were evaluated. Results. All patients (22 eyes)
      completed the study and surgeries lasted less than 60 minutes. All wounds were
      obliquely performed, 23-gauge mean angle was 23 +/- 5 degrees , and 25-gauge
      angule was 21 +/- 4 degrees . Twenty-three-gauge sclerotomy transversal mean
      length was 1122 +/- 242  MU m and 25-gauge transversal sclerotomy mean length was
      977 +/- 174  MU m; 23-gauge longitudinal mean length was 363 +/- 42  MU m and 25
      gauge longitudinal sclerotomy mean length was 234 +/-19  MU m; 23-gauge open
      wound thickness mean was 61 +/- 28  MU m and 25-gauge open wound thickness mean
      was 22 +/- 6  MU m. All results were statistically significant (P < 0.05). No
      vitreous incarceration or silicone oil residue was observed in incision sites
      with both gauges. Conclusions. The 23-gauge and 25-gauge architectural wound
      constructions were well visualized using CAM SD-OCT. Statistical differences
      between the two gauges were observed throughout the study period.

PMID- 23533706
TI  - Sustained and Transient Contributions to the Rat Dark-Adapted Electroretinogram b
      Wave.
AB  - The most dominant feature of the electroretinogram, the b-wave, is thought to
      reflect ON-bipolar cell responses. However, a number of studies suggest that the
      b-wave is made up of several components. We consider the composition of the rat b
      wave by subtracting corneal negative components obtained using intravitreal
      application of pharmacological agents to remove postreceptoral responses. By
      analyzing the intensity-response characteristic of the PII across a range of
      fixed times during and after a light step, we find that the rat isolated PII has
      2 components. The first has fast rise and decay characteristics with a low
      sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient
      ON component to manifest increased and deceased sensitivity to light at shorter
      (<160 ms) and longer times, respectively. The second component has slower
      temporal characteristics but is more sensitive to light. GABAc-mediated
      inhibition enhances this sustained-ON component but has little effect on its
      sensitivity to light. After stimulus offset, both transient and sustained
      components return to baseline, and a long latency sustained positive component
      becomes apparent. The light sensitivities of transient-ON and sustained-OFF
      components are consistent with activity arising from cone ON- and OFF-bipolar
      cells, whereas the sustained-ON component is likely to arise from rod bipolar
      cells.

PMID- 23533707
TI  - Effects of Vitrectomy on Recurrent Macular Edema due to Branch Retinal Vein
      Occlusion after Intravitreal Injection of Bevacizumab.
AB  - Purpose. To evaluate the effects of pars plana vitrectomy (PPV) on recurrent
      macular edema due to branch retinal vein occlusion (BRVO) after intravitreal
      injections of bevacizumab (IVB). Methods. This retrospective study included 22
      eyes of 22 patients who underwent single or multiple IVB injections for macular
      edema due to BRVO and showed a recurrence of macular edema. All patients then
      underwent PPV and were followed up for more than 6 months after the surgery with
      examinations of best corrected visual acuity (BCVA) and optical coherence
      tomography (OCT). OCT parameters were central macular thickness (CMT) and average
      retinal thickness in a 1-mm-diameter circular region at the fovea (MRT). Results.
      Mean BCVA, CRT, and MRT were significantly improved from the baseline after PPV.
      Greater improvement of BCVA, CRT, and MRT was obtained after 1 month of IVB than
      after 6 months of PPV. No eyes showed worsening of macular edema after the
      surgery. Conclusion. PPV improved BCVA and recurrent macular edema due to BRVO,
      but PPV that was less effective than IVB had been in the same patients. PPV may
      be one of the treatment options for recurrent macular edema due to BRVO after
      IVB.

PMID- 23533708
TI  - Long-term followup comparing two treatment dosing strategies of (125) I plaque
      radiotherapy in the management of small/medium posterior uveal melanoma.
AB  - Objective. To investigate the efficacy of two different dosing strategies of
      radioactive iodine-125 ((125)I) in the management of small- and medium-sized
      posterior uveal melanoma. Patients and Methods. The medical records of
      consecutive patients with choroidal melanomas between 1.5 and 5.0 mm in apical
      height treated initially with (125)I plaque radiotherapy were reviewed. Patients
      were treated with one of the following two treatment dosing strategies: (1) 85 Gy
      to the apical height of the tumor (group 1) or (2) 85 Gy to a prescription point
      of 5.0 mm (group 2). Results. Of 95 patients, 55 patients were treated to the
      apical height of the tumor, and 40 were treated to a prescription point of 5.0
      mm. Comparative analysis of the incidence rates of specific complications between
      the two groups demonstrates that group 2 had a significantly higher incidence of
      radiation retinopathy, radiation optic neuropathy, and/or visually significant
      cataract formation than group 1 (P = 0.028). Conclusion. Treatment of choroidal
      melanomas less than 5 mm in apical height with (125)I brachytherapy to the true
      apical height is equally effective when compared to treatment with 85 Gy to 5.0
      mm. Treatment to the apical height of the tumor may result in lower incidence of
      radiation-related complications.

PMID- 23533709
TI  - Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors.
AB  - Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the
      formation of prostaglandins, which are mediators of inflammation. It exists
      mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti
      inflammatory drugs (NSAIDs) have gastrointestinal side effects because they
      inhibit both isoforms. Recent data demonstrate that the overexpression of these
      enzymes, and in particular of cyclooxygenases-2, promotes multiple events
      involved in tumorigenesis; in addition, numerous studies show that the inhibition
      of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that
      inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic
      development and offer a new perspective for a further use of COX-2 inhibitors.
      The present study extends the evaluation of the COX activity to all 20(3)
      possible natural tripeptide sequences following a rational approach consisting in
      molecular modeling, synthesis, and biological tests. Based on data obtained from
      virtual screening, only those peptides with better profile of affinity have been
      selected and classified into two groups called S and E. Our results suggest that
      these novel compounds may have potential as structural templates for the design
      and subsequent development of the new selective COX-2 inhibitors drugs.

PMID- 23533710
TI  - Potential anticarcinogenic peptides from bovine milk.
AB  - BOVINE MILK POSSESSES A PROTEIN SYSTEM CONSTITUTED BY TWO MAJOR FAMILIES OF
      PROTEINS: caseins (insoluble) and whey proteins (soluble). Caseins ( alpha S1,
      alpha S2, beta , and kappa ) are the predominant phosphoproteins in the milk of
      ruminants, accounting for about 80% of total protein, while the whey proteins,
      representing approximately 20% of milk protein fraction, include beta 
      lactoglobulin, alpha -lactalbumin, immunoglobulins, bovine serum albumin, bovine
      lactoferrin, and lactoperoxidase, together with other minor components. Different
      bioactivities have been associated with these proteins. In many cases, caseins
      and whey proteins act as precursors of bioactive peptides that are released, in
      the body, by enzymatic proteolysis during gastrointestinal digestion or during
      food processing. The biologically active peptides are of particular interest in
      food science and nutrition because they have been shown to play physiological
      roles, including opioid-like features, as well as immunomodulant,
      antihypertensive, antimicrobial, antiviral, and antioxidant activities. In recent
      years, research has focused its attention on the ability of these molecules to
      provide a prevention against the development of cancer. This paper presents an
      overview of antitumor activity of caseins and whey proteins and derived peptides.

PMID- 23533711
TI  - Urotensin-II Ligands: An Overview from Peptide to Nonpeptide Structures.
AB  - Urotensin-II was originally isolated from the goby urophysis in the 1960s as a
      vasoactive peptide with a prominent role in cardiovascular homeostasis. The
      identification of human isoform of urotensin-II and its specific UT receptor by
      Ames et al. in 1999 led to investigating the putative role of the interaction U
      II/UT receptor in multiple pathophysiological effects in humans. Since urotensin
      II is widely expressed in several peripheral tissues including cardiovascular
      system, the design and development of novel urotensin-II analogues can improve
      knowledge about structure-activity relationships (SAR). In particular, since the
      modulation of the U-II system offers a great potential for therapeutic strategies
      related to the treatment of several diseases, like cardiovascular diseases, the
      research of selective and potent ligands at UT receptor is more fascinating. In
      this paper, we review the developments of peptide and nonpeptide U-II structures
      so far developed in order to contribute also to a more rational and detectable
      design and synthesis of new molecules with high affinity at the UT receptor.

PMID- 23533713
TI  - Improved Hypertension Control with the Imidazoline Agonist Moxonidine in a
      Multinational Metabolic Syndrome Population: Principal Results of the MERSY
      Study.
AB  - This study was designed to assess the effects of moxonidine on blood pressure and
      aspects of the metabolic syndrome in racially diverse population of patients
      encountered in routine medical practice. Physicians collected data on a minimum
      of three consecutive patients with uncontrolled essential hypertension and
      criteria for metabolic syndrome, eligible to receive moxonidine (0.2-0.4 mg once
      daily) for 6 months, either as monotherapy or as adjunct therapy to current
      antihypertensive treatment. Systolic and diastolic blood pressure (BP) declined
      by an average of 24.5 + 14.3 mmHg and 12.6 + 9.1 mmHg, respectively. BP responder
      rates defined as attaining BP < 140/90 mmHg were significantly (P < 0.001) and
      substantially higher among younger patients, nonpostmenopausal women, and
      patients receiving monotherapy. While potentially relevant improvements in the
      entire cohort were observed in regard to body weight (-2.1 +/- 5.4 kg), fasting
      plasma glucose (from 6.8 to 6.2 mmol/L), and triglycerides (2.4 to 2.0 mmol/L),
      statistically significant changes in metabolic parameters could only be detected
      in subgroup analyses. Moxonidine therapy reduced blood pressure and improved
      rates of blood pressure control in this group of patients. While the observed
      trend towards improvement in various metabolic parameters merits further
      investigation, the overall effect of moxonidine treatment is consistent with a
      reduction of total cardiovascular risk in this hypertensive metabolic syndrome
      cohort.

PMID- 23533712
TI  - Adult medication-free schizophrenic patients exhibit long-chain omega-3 Fatty
      Acid deficiency: implications for cardiovascular disease risk.
AB  - Deficiency in long-chain omega-3 (LCn - 3) fatty acids, eicosapentaenoic acid
      (EPA, 20:5n - 3) and docosahexaenoic acid (DHA, 22:6n - 3), has been implicated
      in the pathoetiology of cardiovascular disease, a primary cause of excess
      premature mortality in patients with schizophrenia (SZ). In the present study, we
      determined erythrocyte EPA + DHA levels in adult medication-free patients SZ (n =
      20) and age-matched healthy controls (n = 24). Erythrocyte EPA + DHA composition
      exhibited by SZ patients (3.5%) was significantly lower than healthy controls
      (4.5%, -22%, P = 0.007). The majority of SZ patients (72%) exhibited EPA+DHA
      levels <=4.0% compared with 37% of controls (Chi-square, P = 0.001). In contrast,
      the omega-6 fatty acid arachidonic acid (AA, 20:4n - 6) (+9%, P = 0.02) and the
      AA:EPA + DHA ratio (+28%, P = 0.0004) were significantly greater in SZ patients.
      Linoleic acid (18:2n - 6) was significantly lower (-12%, P = 0.009) and the
      erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was
      significantly elevated in SZ patients. Compared with same-gender controls, EPA +
      DHA composition was significantly lower in male (-19%, P = 0.04) but not female (
      13%, P = 0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly
      elevated in both male (+22%, P = 0.008) and female (+22%, P = 0.04) SZ patients.
      These results suggest that the majority of SZ patients exhibit low LCn - 3 fatty
      acid levels which may place them at increased risk for cardiovascular morbidity
      and mortality.

PMID- 23533714
TI  - Prevalence, awareness, and treatment of hypertension in patients with type 1
      diabetes: a nationwide multicenter study in Brazil.
AB  - Objective. This study evaluated the prevalence, awareness, and type of treatment
      for hypertension in Brazil in patients with type 1 diabetes (T1D). Methods. This
      was a cross-sectional, multicenter study that was conducted from December 2008 to
      December 2010 in 28 public clinics located in 20 Brazilian cities. Results. A
      total of 3,591 patients were studied, 56% female, average age 21.2 +/- 11.7
      years, with a median duration of diabetes 9.6 +/- 8.1 years. Blood pressure
      levels were available for a total of 3,323 patients and 689 (19.2%) patients were
      hypertensive. Hypertensive patients were older, exhibited longer duration of
      diabetes, and had higher body mass index (BMI), total cholesterol, triglycerides,
      and LDL-C values (P < 0.001, for all comparisons), but only 370 (53.7%) received
      treatment. Patient awareness of hypertension was documented in 453 (65.5%)
      patients. However, only 76 (22.9%) of the treated patients attained the target
      systolic (sBP) and diastolic blood pressures (dBP). Conclusions. Our results
      demonstrate that a large number of T1D patients with hypertension do not receive
      appropriate treatment; few of the treated T1D patients achieved the target sBP
      and dBP values. Greater attention should be paid to blood pressure evaluation,
      hypertension diagnosis, and treatment of T1D patients in Brazil.

PMID- 23533716
TI  - Characterisation of hypertensive patients with improved endothelial function
      after dark chocolate consumption.
AB  - Recent findings indicate an inverse relationship between cardiovascular disease
      and consumption of flavonoids. We aimed to identify clinical and vascular
      parameters of treated hypertensive who present beneficial effects of dark
      chocolate for one-week period on vascular function. Twenty-one hypertensive
      subjects, aged 40-65 years, were included in a prospective study with measurement
      of blood pressure (BP), brachial flow-mediated dilatation (FMD), peripheral
      arterial tonometry, and central hemodynamic parameters. These tests were repeated
      after seven days of eating dark chocolate 75 g/day. Patients were divided
      according to the response in FMD: responders (n = 12) and nonresponders (n = 9).
      The responder group presented lower age (54 +/- 7 versus 61 +/- 6 years, P =
      0.037), Framingham risk score (FRS) (2.5 +/- 1.8 versus 8.1 +/- 5.1%, P = 0.017),
      values of peripheral (55 +/- 9 versus 63 +/- 5 mmHg, P = 0.041), and central
      pulse pressure (PP) (44 +/- 10 versus 54 +/- 6 mmHg, P = 0.021). FMD response
      showed negative correlation with FRS (r = -0.60, P = 0.014), baseline FMD (r = 
      0.54, P = 0.011), baseline reactive hyperemia index (RHI; r = -0.56, P = 0.008),
      and central PP (r = -0.43, P = 0.05). However, after linear regression analysis,
      only FRS and baseline RHI were associated with FMD response. In conclusion, one
      week dark chocolate intake significantly improved endothelial function and
      reduced BP in younger hypertensive with impaired endothelial function in spite of
      lower cardiovascular risk.

PMID- 23533717
TI  - Purification and Properties of White Muscle Lactate Dehydrogenase from the Anoxia
      Tolerant Turtle, the Red-Eared Slider, Trachemys scripta elegans.
AB  - Lactate dehydrogenase (LDH; E.C. 1.1.1.27) is a crucial enzyme involved in energy
      metabolism in muscle, facilitating the production of ATP via glycolysis during
      oxygen deprivation by recycling NAD(+). The present study investigated purified
      LDH from the muscle of 20 h anoxic and normoxic T. s. elegans, and LDH from
      anoxic muscle showed a significantly lower (47%) K m for L-lactate and a higher V
      max value than the normoxic form. Several lines of evidence indicated that LDH
      was converted to a low phosphate form under anoxia: (a) stimulation of
      endogenously present protein phosphatases decreased the K m of L-lactate of
      control LDH to anoxic levels, whereas (b) stimulation of kinases increased the K
      m of L-lactate of anoxic LDH to normoxic levels, and (c) dot blot analysis shows
      significantly less serine (78%) and threonine (58%) phosphorylation in anoxic
      muscle LDH as compared to normoxic LDH. The physiological consequence of anoxia
      induced LDH dephosphorylation appears to be an increase in LDH activity to
      promote the reduction of pyruvate in muscle tissue, converting the glycolytic end
      product to lactate to maintain a prolonged glycolytic flux under energy-stressed
      anoxic conditions.

PMID- 23533715
TI  - Impact of diabetes on cardiovascular disease: an update.
AB  - Cardiovascular diseases are the most prevalent cause of morbidity and mortality
      among patients with type 1 or type 2 diabetes. The proposed mechanisms that can
      link accelerated atherosclerosis and increased cardiovascular risk in this
      population are poorly understood. It has been suggested that an association
      between hyperglycemia and intracellular metabolic changes can result in oxidative
      stress, low-grade inflammation, and endothelial dysfunction. Recently, epigenetic
      factors by different types of reactions are known to be responsible for the
      interaction between genes and environment and for this reason can also account
      for the association between diabetes and cardiovascular disease. The impact of
      clinical factors that may coexist with diabetes such as obesity, dyslipidemia,
      and hypertension are also discussed. Furthermore, evidence that justify screening
      for subclinical atherosclerosis in asymptomatic patients is controversial and is
      also matter of this review. The purpose of this paper is to describe the
      association between poor glycemic control, oxidative stress, markers of insulin
      resistance, and of low-grade inflammation that have been suggested as putative
      factors linking diabetes and cardiovascular disease.

PMID- 23533718
TI  - Optimization and Immobilization of Purified Labeo rohita Visceral Protease by
      Entrapment Method.
AB  - The purified fish visceral protease enzyme was immobilized by using various
      concentrations of sodium alginate and calcium chloride to optimize the best
      concentration for the formation of the beads. Then it was characterized by
      assaying the optimal pH, temperature, storage stability and reusability. The
      results on immobilization with sodium alginate and calcium chloride showed that a
      combination of 2% sodium alginate and 0.3 M calcium chloride weas found to be the
      optimum concentration for the formation of spherical and stable beads, this gave
      a maximal entrapped activity of 48.31%, and there was no change in the optimum pH
      8.0 and temperature 40 degrees C of protease before and after entrapment. The
      results on stability and reusability indicated that it was stable at 4 degrees C
      retaining 100% residual activity after 5 days of storage and 67% loss of activity
      after ten days of storage and it retained 100% residual activity on the first
      reuse, 75% residual activity on the second reuse, 25% residual activity on the
      third use and complete loss in the activity on the fourth reuse.

PMID- 23533719
TI  - Posttranslational Protein Modification in the Salivary Glands of Sjogren's
      Syndrome Patients.
AB  - The present study investigated posttranslational reactions in the salivary glands
      of patients with Sjogren's syndrome. We analysed the biopsies of primary
      Sjogren's patients using immunohistochemistry and a tag-purified anticyclic
      citrullinated protein (CCP) antibody to detect citrullinated peptides, and the
      presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The
      present work demonstrated the weak presence of the PAD2 enzyme in some normal
      salivary glands, although PAD2 expression was increased considerably in Sjogren's
      patients. The presence of citrullinated proteins was also detected in the
      salivary tissues of Sjogren's patients, which strongly supports the in situ
      posttranslational modification of proteins in this setting. Furthermore, the
      mutual expression of CCP and PAD2 suggests that this posttranslational
      modification is enzyme dependent. In conclusion, patients with Sjogren's syndrome
      expressed the catalytic machinery to produce posttranslational reactions that may
      result in autoantigen triggering.

PMID- 23533720
TI  - Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced
      changes in rat adipose deposition.
AB  - Intrauterine growth restriction (IUGR) predisposes to obesity and adipose
      dysfunction. We previously demonstrated IUGR-induced increased visceral adipose
      deposition and dysregulated expression of peroxisome proliferator activated
      receptor- gamma 2 (PPAR gamma 2) in male adolescent rats, prior to the onset of
      obesity. In other studies, activation of PPAR gamma increases subcutaneous
      adiponectin expression and normalizes visceral adipose deposition. We
      hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a
      PPAR gamma agonist, would normalize IUGR adipose deposition in association with
      increased PPAR gamma , adiponectin, and adiponectin receptor expression in
      subcutaneous adipose. To test these hypotheses, we used a well-characterized
      model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with
      maternal DHA supplementation. Our primary findings were that maternal DHA
      supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced
      changes in adipose deposition and visceral PPAR gamma expression in male rats and
      (2) increases serum adiponectin, as well as adipose expression of adiponectin and
      adiponectin receptors in former IUGR rats. Our novel findings suggest that
      maternal DHA supplementation may normalize adipose dysfunction and promote
      adiponectin-induced improvements in metabolic function in IUGR.

PMID- 23533721
TI  - Black/white differences in perceived weight and attractiveness among overweight
      women.
AB  - Numerous studies have reported that Black women are more satisfied with their
      bodies than White women. The buffering hypothesis suggests that aspects of Black
      culture protect Black women against media ideals that promote a slender female
      body type; therefore, Black women are expected to exhibit higher body esteem than
      White women. To test this hypothesis, the current study aimed to assess the
      influence of race on weight perception, perceived attractiveness, and the
      interrelations between body mass index (BMI) and perceived attractiveness among
      overweight and obese women. Participants were 1,694 respondents of Wave IV of the
      National Longitudinal Study on Adolescent Health (M = 28.89 years). Black (n =
      531) or White (n = 1163) obese or overweight women were included in the current
      study. As expected, Black women reported lower perceived weight and higher
      attractiveness than White women, despite higher body mass for Black women.
      Furthermore, race moderated the relationship between BMI and perceived
      attractiveness; for White women, a negative relationship existed between BMI and
      attractiveness, whereas for Black women, BMI and attractiveness were not related.
      The study findings provide further support for the buffering hypothesis,
      indicating that despite higher body mass, overweight Black women are less
      susceptible to thin body ideals than White women.

PMID- 23533722
TI  - Metabolic risk susceptibility in men is partially related to adiponectin/leptin
      ratio.
AB  - BACKGROUND: High adiponectin/leptin ratio may be protective from metabolic risks
      imparted by high triglyceride, low HDL, and insulin resistance. METHODS: This
      cross-sectional study examines plasma adipokine levels in 428 adult men who were
      subgrouped according to low (<6.5  MU g/mL)and high (>=6.5  MU g/mL)adiponectin
      levels or a low or high ratio of adiponectin/leptin. RESULTS: Men with high
      adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol
      than those with low ratio. Similarly, those with high adiponectin/leptin ratio
      had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In
      contrast, levels of adiponectin or the ratio of adiponectin/leptin did not
      associate with systolic blood pressure. But the ratio of adiponectin/leptin
      decreased progressively with the increase in the number of risk factors for
      metabolic syndrome. CONCLUSION: Adipokine levels may reflect adipose tissue
      triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat
      mass, and adiponectin is a biomarker of triglyceride metabolism and insulin
      sensitivity. Men with high adiponectin/leptin ratios have better triglyceride
      profile and insulin sensitivity than men with a low ratio regardless of waist
      girth.

PMID- 23533723
TI  - "Obese equals lazy?" analysis of the association between weight status and
      physical activity in children.
AB  - INTRODUCTION: Literature provides evidence that overweight children are more
      sedentary. To verify this generalized statement behavior patterns of overweight
      and nonoverweight children needs to be understood. Therefore, we investigated the
      distribution of sedentary and activity levels in a quantitative and qualitative
      way. METHODS: Data was collected from 37 randomly selected nonoverweight and 55
      overweight children. They were 8 to 11 years of age. Height and weight were
      measured and weight status was characterized by BMI (BMI-percentile, BMI-SDS).
      Daily PA (physical activity) was measured by direct accelerometry. Spare time and
      screen time entertainment were obtained by questionnaires. RESULTS: The amount of
      time spent "passive" was significantly higher in overweight children, while
      nonoverweight children were more "active." The multiple regression model shows a
      significant association between weight status (BMI-SDS) and activity parameters.
      Additionally, screen time entertainment was significantly related to BMI-SDS.
      CONCLUSION: The results support the statement that overweight children are less
      active than nonoverweight children. The high amount of PA seems to be an
      important factor to prevent overweight in children given that PA shows the
      highest correlation to weight status. Quantitative and qualitative measurements
      are needed for further analysis.

PMID- 23533724
TI  - PTPIP51: a new interaction partner of the insulin receptor and PKA in adipose
      tissue.
AB  - AIMS: Our previous experiments revealed an association of PTPIP51 (protein
      tyrosine phosphatase interacting protein 51) with the insulin signalling pathway
      through PTP1B and 14-3-3beta. We aimed to clarify the role of PTPIP51 in
      adipocyte metabolism. METHODS: Four groups of ten C57Bl/6 mice each were used.
      Two groups were fed a standard diet; two groups were fed a high-fat diet. Two
      groups (one high-fat diet and one standard diet) were submitted to endurance
      training, while the remaining two groups served as untrained control groups.
      After ten weeks, we measured glucose tolerance of the mice. Adipose tissue
      samples were analyzed by immunofluorescence and Duolink proximity ligation assay
      to quantify interactions of PTPIP51 with either insulin receptor (IR) or PKA.
      RESULTS: PTPIP51 and the IR and PTPIP51 and PKA, respectively, were colocalized
      in all groups. Standard diet animals that were submitted to endurance training
      showed low PTPIP51-IR and PTPIP51-PKA interactions. The interaction levels of
      both the IR and PKA differed between the feeding and training groups. CONCLUSION:
      PTPIP51 might serve as a linking protein in adipocyte metabolism by connecting
      the IR-triggered lipogenesis with the PKA-dependent lipolysis. PTPIP51 interacts
      with both proteins, therefore being a potential gateway for the cooperation of
      both pathways.

PMID- 23533725
TI  - Weight-loss interventions for Hispanic populations: the role of culture.
AB  - In the United States, ethnic minorities are overrepresented among the overweight
      and obese population, with Hispanic individuals being among the groups most at
      risk for obesity and obesity-related disease and disability. Most weight-loss
      interventions designed for the general population have been less successful with
      individuals from ethnic minorities and there is a pressing need to develop more
      effective interventions for these groups. This paper examines the importance of
      culture in the development of "culturally competent" weight-loss interventions
      for ethnic minority populations, and discusses specific culturally mediated
      factors that should be considered in the design and implementation of treatment
      interventions. While specifically focusing on Hispanic populations, we also
      address issues of relevance to other multiethnic societies.

PMID- 23533726
TI  - The relationship between executive function and obesity in children and
      adolescents: a systematic literature review.
AB  - The objective of this paper is to examine the relationship between the
      development of executive function (EF) and obesity in children and adolescents.
      We reviewed 1,065 unique abstracts: 31 from PubMed, 87 from Google Scholar, 16
      from Science Direct, and 931 from PsycINFO. Of those abstracts, 28 met inclusion
      criteria and were reviewed. From the articles reviewed, an additional 3 articles
      were added from article references (N = 31). Twenty-three studies pertained to EF
      (2 also studied the prefrontal and orbitofrontal cortices (OFCs); 6 also studied
      cognitive function), five studied the relationship between obesity and prefrontal
      and orbitofrontal cortices, and three evaluated cognitive function and obesity.
      Inhibitory control was most often studied in both childhood (76.9%) and
      adolescent (72.7%) studies, and obese children performed significantly worse (P <
      0.05) than healthy weight controls on various tasks measuring this EF domain.
      Although 27.3% of adolescent studies measured mental flexibility, no childhood
      studies examined this EF domain. Adolescents with higher BMI had a strong
      association with neurostructural deficits evident in the OFC. Future research
      should be longitudinal and use a uniform method of EF measurement to better
      establish causality between EF and obesity and consequently direct future
      intervention strategies.

PMID- 23533727
TI  - Indices of abdominal adiposity and cardiorespiratory fitness test performance in
      middle-school students.
AB  - BACKGROUND: Previous research suggests that use of BMI as a screening tool to
      assess health in youth has limitations. Valid alternative measures to assess body
      composition are needed to accurately identify children who are aerobically fit,
      which is an indicator of health status. The purpose of this study was to examine
      the associations between select anthropometric measures and cardiorespiratory
      fitness test performance in middle-school students. METHODS: Participants
      included 134 students (65 boys and 69 girls) recruited from the 6th, 7th, and 8th
      grades. Anthropometric measures consisted of BMI, waist circumference (WC), waist
      to-height ratio (WHtR), and percent body fat estimated from two-site skinfolds
      (%BF-SKF), as well as the hand-held OMRON BIA device (%BF-BIA). Cardiorespiratory
      fitness tests included the one-mile run and PACER test. Data were collected on
      four separate testing days during the students' physical education classes.
      RESULTS: There were statistically significant moderate correlations between the
      %BF estimations, WHtR, and cardiorespiratory fitness test scores in both genders
      (P < .001). BMI at best only displayed weak correlations with the
      cardiorespiratory fitness test scores. CONCLUSIONS: The results suggest that
      alternative measures such as %BF-SKF, %BF-BIA, and WHtR may be more valid
      indicators of youth aerobic fitness lending to their preferred use over BMI.

PMID- 23533728
TI  - Organized sports, overweight, and physical fitness in primary school children in
      Germany.
AB  - Physical inactivity is associated with poor physical fitness and increased body
      weight. This study examined the relationship between participation in organized
      sports and overweight as well as physical fitness in primary school children in
      southern Germany. Height, weight, and various components of physical fitness were
      measured in 995 children (7.6 +/- 0.4 years). Sports participation and
      confounding variables such as migration background, parental education, parental
      body weight, and parental sports participation were assessed via parent
      questionnaire. Multiple logistic regression as well as multivariate analysis of
      covariance (MANCOVA) was used to determine associations between physical fitness,
      participation in organized sports, and body weight. Participation in organized
      sports less than once a week was prevalent in 29.2%, once or twice in 60.2%, and
      more often in 10.6% of the children. Overweight was found in 12.4% of the
      children. Children participating in organized sports more than once per week
      displayed higher physical fitness and were less likely to be overweight (OR  = 
      0.52, P < 0.01). Even though causality cannot be established, the facilitation of
      participation in organized sports may be a crucial aspect in public health
      efforts addressing the growing problems associated with overweight and obesity.

PMID- 23533729
TI  - The Association between Noncommercial Partnerships and Risk of HIV among Female
      Sex Workers: Evidences from a Cross-Sectional Behavioral and Biological Survey in
      Southern India.
AB  - This paper examines the association between female sex workers' (FSWs)
      noncommercial partnerships with risk of HIV in Andhra Pradesh, India. Data were
      drawn from a cross-sectional behavioral and biological survey conducted in 2009
      among 3225 FSWs from Andhra Pradesh. Participants were asked about their sexual
      partnerships, condom use, and vulnerability factors and tested for HIV and
      sexually transmitted infections. The key independent variables considered were
      presence of a noncommercial sexual partner (no, yes) and the nature of such
      partnerships (regular, nonregular). FSWs who reported husband as noncommercial
      partner were considered to have a regular partner, while the rest were defined as
      having nonregular partners. Adjusted odds ratios (OR) and 95% confidence
      intervals (CI) were estimated to measure the associations between variables of
      interest. Almost three-fourths (74.8%) of FSWs reported having noncommercial
      partners (regular: 55.6%; nonregular: 19.3%). FSWs in nonregular partnerships
      were more likely to be HIV positive (13.1% versus 10.9%, adjusted OR: 1.4, 95%
      CI: 1.1-1.8), have syphilis (10.3% versus 4.2%, adjusted OR: 2.3, 95% CI: 1.6
      3.3), use condoms inconsistently with occasional clients (21.0% versus 16.5%,
      adjusted OR: 1.5, 95% CI: 1.2-1.9), and report forced sex (25.1% versus 14.1%,
      adjusted OR: 1.9, 95% CI: 1.5-2.4) as compared to those in regular partnerships.
      HIV prevention programs need to emphasize safe sex behaviors, particularly among
      FSWs who have nonregular partners.

PMID- 23533730
TI  - Performance of Clinical Criteria for Screening of Possible Antiretroviral Related
      Mitochondrial Toxicity in HIV-Infected Children in Accra.
AB  - Mitochondrial damage is implicated in highly active antiretroviral therapy
      (HAART) toxicity. HIV infection also causes mitochondrial toxicity (MT).
      Differentiating between the two is critical for HIV management. Our objective was
      to test the utility of the Mitochondrial Disease Criteria (MDC) and the Enquete
      Perinatale Francaise (EPF) to screen for possible HAART related MT in HIV
      infected children in Ghana. The EPF and MDC are compilations of clinical
      symptoms, or criteria, of MT: a (+) score indicates possible MT. We applied these
      criteria retrospectively to 403 charts of HIV-infected children. Of those
      studied, 331/403 received HAART. Comparing HAART exposed and HAART naive
      children, the difference in EPF score, but not MDC, approached significance (P =
      0.1). Young age at HIV diagnosis or at HAART initiation was associated with (+)
      EPF (P <= 0.01). Adherence to HAART trended toward an association with (+) EPF (P
      = 0.09). Exposure to nevirapine, abacavir, or didanosine increased risk of (+)
      EPF (OR = 3.55 (CI = 1.99-6.33), 4.76 (2.39-9.43), 4.93 (1.29-18.87)). Neither
      EPF nor MDC identified a significant difference between HAART exposed or naive
      children regarding possible MT. However, as indicators of HAART exposure are
      associated with (+) EPF, it may be a candidate for prospective study of possible
      HAART related MT in resource-poor settings.

PMID- 23533731
TI  - Patterns of Use and Outcomes in Patients Treated with Etravirine in the HIV
      Research Network.
AB  - This observational analysis examined the clinical outcomes of patients receiving
      etravirine-(ETR-) based therapy, particularly with protease inhibitors (PIs)
      other than darunavir (DRV) and with raltegravir (RAL). Data included treatment
      experienced adults in the HIV Research Network who began ETR-containing
      antiretroviral regimens in 2008-2010. The primary objective was to assess 6-month
      outcomes (durability, i.e., still on an ETR-containing regimen; change in CD4+
      cell count and HIV-1 RNA <400 copies/mL). The cohort included 587 patients
      receiving ETR; 42% of ETR use was in patients not on DRV/ritonavir (r). Patients
      receiving ETR plus DRV/r had longer durability versus those on ETR plus a PI
      other than DRV/r at months 6 (91.2% versus 85.5%) and 12 (77.4% versus 65.2%),
      respectively. Patients on regimens with a PI other than DRV/r were the least
      likely to be receiving ETR at month 6 (85.5%) versus patients on other ETR-based
      regimens. Patients on regimens without a PI and without RAL had lower virologic
      suppression (month 6, 54.2%; month 12, 63.2%) versus patients on other ETR-based
      regimens. In a clinical care, nontrial setting, ETR was used in regimens without
      DRV/r. In this population, the 6-month response rates were similar and durable
      across all regimens, except when ETR was used without RAL and without a PI.

PMID- 23533732
TI  - HIV-Associated Central Nervous System Disease in Patients Admitted at the Douala
      General Hospital between 2004 and 2009: A Retrospective Study.
AB  - Background. Studies on HIV-associated central nervous system (CNS) diseases in
      Cameroon are rare. The aim of this study was to describe the clinical
      presentation, identify aetiological factors, and determine predictors of
      mortality in HIV patients with CNS disease. Methods. From January 1, 2004 and
      December 31, 2009, we did at the Douala General Hospital a clinical case note
      review of 672 admitted adult (age >= 18 years) HIV-1 patients, and 44.6%
      (300/672) of whom were diagnosed and treated for HIV-associated CNS disease.
      Results. The mean age of the study population was 38.1 +/- 13.5 years, and median
      CD4 count was 49 cells/mm(3) (interquartile range (QR): 17-90). The most common
      clinical presentations were headache (83%), focal signs (40.6%), and fever
      (37.7%). Toxoplasma encephalitis and cryptococcal meningitis were the leading
      aetiologies of HIV-associated CNS disease in 32.3% and 25% of patients,
      respectively. Overall mortality was 49%. Primary central nervous system lymphoma
      (PCNSL) and bacterial meningitis had the highest case fatality rates of 100%
      followed by tuberculous meningitis (79.8%). Low CD4 count was an independent
      predictor of fatality (AOR: 3.2, 95%CI: 2.0-5.2). Conclusions. HIV-associated CNS
      disease is common in Douala. CNS symptoms in HIV patients need urgent
      investigation because of their association with diseases of high case fatality.

PMID- 23533733
TI  - Developing multipurpose reproductive health technologies: an integrated strategy.
AB  - WOMEN WORLDWIDE CONFRONT TWO FREQUENTLY CONCURRENT REPRODUCTIVE HEALTH
      CHALLENGES: the need for contraception and for protection from sexually
      transmitted infections, importantly HIV/AIDS. While conception and infection
      share the same anatomical site and mode of transmission, there are no
      reproductive health technologies to date that simultaneously address that
      reality. Relevant available technologies are either contraceptive or anti
      infective, are limited in number, and require different modes of administration
      and management. These "single-indication" technologies do not therefore fully
      respond to what is a substantial reproductive health need intimately linked to
      pivotal events in many women's lives. This paper reviews an integrated attempt to
      develop multipurpose prevention technologies-"MPTs"-products explicitly designed
      to simultaneously address the need for both contraception and protection from
      sexually transmitted infections. It describes an innovative and iterative MPT
      product development strategy with the following components: identifying different
      needs for such technologies and global variations in reproductive health
      priorities, defining "Target Product Profiles" as the framework for a research
      and development "roadmap," collating an integrated MPT pipeline and
      characterizing significant pipeline gaps, exploring anticipated regulatory
      requirements, prioritizing candidates for problem-solving and resource
      investments, and implementing an ancillary advocacy agenda to support this
      breadth of effort.

PMID- 23533734
TI  - HDL-C Response Variability to Niacin ER in US Adults.
AB  - Background. Niacin is the most effective treatment currently available for
      raising HDL-C levels. Objective. To evaluate if gender and baseline lipid levels
      have an effect on the HDL-C response of niacin ER and to identify factors that
      predict response to niacin ER at the 500 mg dose. Material and Methods. The
      change in HDL-C effect between baseline and follow-up levels was quantified in
      absolute change as well as dichotomized into high versus low response (high
      response was defined as an HDL-C effect of >15% increase and low response was HDL
      C <5%) in a sample of 834 individuals. Results. Both males and females with low
      HDL-C levels at baseline exhibited a response to treatment in the multivariate
      model (males, HDL-C <40 mg/dL: OR = 5.18, 95% CI: 2.36-11.39; females, HDL-C <50
      mg/dL: OR = 5.40, 95% CI: 1.84-15.79). There was also a significant difference in
      the mean HDL-C effect between baseline and follow-up HDL-C levels in the 500 mg
      niacin ER dose group for both males (mean HDL-C effect = 0.08, P < 0.001) and
      females (mean HDL-C effect = 0.10, P = 0.019). Conclusion. Baseline HDL-C levels
      are the biggest predictor of response to niacin ER treatment for both males and
      females among the factors evaluated.

PMID- 23533735
TI  - Simulations for mechanical ventilation in children: review and future prospects.
AB  - Mechanical ventilation is a very effective therapy, but with many complications.
      Simulators are used in many fields, including medicine, to enhance safety issues.
      In the intensive care unit, they are used for teaching cardiorespiratory
      physiology and ventilation, for testing ventilator performance, for forecasting
      the effect of ventilatory support, and to determine optimal ventilatory
      management. They are also used in research and development of clinical decision
      support systems (CDSSs) and explicit computerized protocols in closed loop. For
      all those reasons, cardiorespiratory simulators are one of the tools that help to
      decrease mechanical ventilation duration and complications. This paper describes
      the different types of simulators described in the literature for physiologic
      simulation and modeling of the respiratory system, including a new simulator
      (SimulResp), and proposes a validation process for these simulators.

PMID- 23533736
TI  - Slowly evolving trends in temporal lobe epilepsy management at london health
      sciences centre.
AB  - Although the advent of MRI impacted significantly our presurgical investigation,
      ictal semiology with interictal and ictal EEG has clearly retained its roles in
      localizing epileptogenesis. MRI-identified lesions considered epileptogenic on
      semiological and electroencephalographic grounds have increased the likelihood of
      resective surgery effectiveness whereas a nonlesional MRI would diminish this
      probability. Ictal propagation and the interplay between its source and
      destination have emerged as a significant component of seizure evaluation over
      the past 30 years.

PMID- 23533737
TI  - Update on temporal lobe epilepsy.

PMID- 23533739
TI  - Hepatitis viruses in heamodialysis patients: an added insult to injury?
AB  - Hepatitis B (HBV) and hepatitis C (HCV) viruses are the most important causes of
      chronic liver disease in patients with end stage renal disease on hemodialysis.
      The prevalence of hepatitis infection among hemodialysis patients is high and
      varies between countries and between dialysis units within a single country. This
      case-control study was undertaken to estimate the occurrence of HBV and HCV
      infections in patients undergoing hemodialysis in our tertiary care center. All
      patients receving hemodialysis at our centre with HCV or HBV infection were
      included in the study. The total number of patients admitted for hemodialysis
      during the study period was 1710. Among these, 26 patients were positive for HBV,
      19 were positive for HCV, and 2 were positive for both HCV and HBV. Mean age of
      the infected cases in our study was 48.63 years. Mean duration of dialysis for
      infected cases was 4.8 years while that of the noninfected controls was 3.18
      years. The mean dialysis interval was twice a week. Interventions to reduce the
      occurrence of these infections are of utmost need to reduce the risk of long-term
      complications among hemodialysis patients.

PMID- 23533738
TI  - Occult hepatitis B: clinical viewpoint and management.
AB  - Occult HBV infection (OBI) is defined as HBV DNA detection in serum or in the
      liver by sensitive diagnostic tests in HBsAg-negative patients with or without
      serologic markers of previous viral exposure. OBI seems to be higher among
      subjects at high risk for HBV infection and with liver disease. OBI can be both a
      source of virus contamination in blood and organ donations and the reservoir for
      full blown hepatitis after reactivation. HBV reactivation depends on viral and
      host factors but these associations have not been analyzed thoroughly. In OBI, it
      would be best to prevent HBV reactivation which inhibits the development of
      hepatitis and subsequent mortality. In diverse cases with insufficient data to
      recommend routine prophylaxis, early identification of virologic reactivation is
      essential to start antiviral therapy. For retrieving articles regarding OBI,
      various databases, including OVID, PubMed, Scopus, and ScienceDirect, were used.

PMID- 23533740
TI  - Monoclonal Antibody Targeting Neutralizing Epitope on H5N1 Influenza Virus of
      Clade 1 and 0 for Specific H5 Quantification.
AB  - H5N1 influenza viruses cause high mortality in avian and mammalian species,
      including humans. Antigenic drift in H5 sequence poses challenges in the
      development of vaccine and therapeutic antibody. In this study, a monoclonal
      antibody 11G12 was produced from inactivated H5N1 immunized mice. Results from
      IFA, ELISA, HI, and virus neutralization indicated that Mab 11G12 can
      specifically recognize and neutralize H5 type hemagglutinin from clade 1 and 0
      without any cross-reaction to any other clades of H5N1 viruses. Mab 11G12 was
      used to differentiate and quantify the expression of H5N1 strain
      A/VietNam/1203/04 from a trivalent vaccine mix in ELISA. Sequencing of escape
      mutants identified that Mab 11G12 targets a major neutralizing epitope of
      influenza H5 hemagglutinin. The study indicated that some major neutralizing
      epitopes in H5s of early strains were mutated due to antigenic drift.

PMID- 23533741
TI  - The role of para-aortic lymphadenectomy in the surgical staging of women with
      intermediate and high-risk endometrial adenocarcinomas.
AB  - Objectives. To characterize clinical outcomes in patients with intermediate or
      high-risk endometrial carcinoma who underwent surgical staging with or without
      para-aortic lymphadenectomy. Methods. This is a retrospective cohort study of
      patients with intermediate or high-risk endometrial adenocarcinoma who underwent
      surgical staging with (PPALN group) or without (PLN) para-aortic lymphadenectomy.
      Data were collected, Kaplan-Meier curves were generated, and univariate and
      multivariate analyses performed to compare differences in adjuvant therapy,
      disease recurrence, disease-free survival (DFS), and overall survival (OS).
      Results. 118 patients were included in the PPALN group and 139 in the PLN group.
      Patients in the PPALN group were more likely to receive adjuvant vaginal
      brachytherapy (25.4% versus 11.5%, OR = 2.5, P = 0.03) and less likely to receive
      adjuvant multimodal combination therapy (17.81% versus 28.8%, OR = 0.28, P =
      0.002). DFS was improved in the PLN group as compared to PPALN (80% versus 62%, P
      = 0.02). OS was equivalent (P = 0.93). Patients in the PPALN group who had less
      than 10 para-aortic nodes removed were twice as likely to recur than patients who
      had 10 or more para-aortic nodes or patients in the PLN group (HR 2.08, CI 1.20
      3.60, P = 0.009). Conclusions. Patients in the PLN group were more likely to
      receive multimodal adjuvant therapy and had better DFS than the PPALN group.
      Pelvic lymphadenectomy followed by adjuvant radiation and chemotherapy may
      represent an effective treatment option for patients with intermediate or high
      risk disease. If systematic para-aortic lymphadenectomy is performed and less
      than 10 para-aortic lymph nodes are obtained, multimodality adjuvant therapy
      should be considered to improve DFS.

PMID- 23533742
TI  - Implementation of stroke Dysphagia screening in the emergency department.
AB  - Early detection of dysphagia is critical in stroke as it improves health care
      outcomes. Administering a swallowing screening tool (SST) in the emergency
      department (ED) appears most logical as it is the first point of patient contact.
      However, feasibility of an ED nurse-administered SST, particularly one involving
      trial water swallow administration, is unknown. The aims of this pilot study were
      to (1) implement an SST with a water swallow component in the ED and track
      nurses' adherence, (2) identify barriers and facilitators to administering the
      SST through interviews, and (3) develop and implement a process improvement plan
      to address barriers. Two hundred seventy-eight individuals with stroke symptoms
      were screened from October 2009 to June 2010. The percentage of patients screened
      increased from 22.6 in October 2009 to a high of 80.8 in March 2010, followed by
      a decrease to 61.9% in June (Cochran-Armitage test z = -5.1042,  P < 0.0001). The
      odds of being screened were 4.0 times higher after implementation compared to two
      months before implementation. Results suggest that it is feasible for ED nurses
      to administer an SST with a water swallow component. Findings should facilitate
      improved quality of care for patients with suspected stroke and improve
      multidisciplinary collaboration in swallowing screening.

PMID- 23533743
TI  - Living with Uncertainty: Older Persons' Lived Experience of Making Independent
      Decisions over Time.
AB  - The aim of the study was to illuminate the meaning of older persons' independent
      decision making concerning their daily care. Autonomy when in care is highly
      valued in the western world. However, research shows that autonomy can give rise
      to problematic issues. The complexity of independence and dependence for older
      people when living at home with help has also been highlighted. In Sweden, older
      people are increasingly expected to live at home with help from municipal home
      care services, and study into this aspect of care is limited. This study is a
      part of an ongoing project and has a qualitative life world perspective.
      Audiotaped narrative interviews were conducted and analysed using a
      phenomenological hermeneutic method. Findings revealed a main theme: "living with
      uncertainty as to how to relate one's own independence and dependence with regard
      to oneself, and others." This involves a constant process of relating to one's
      independence controlled by others or oneself, and adjusting one's independence
      and dependence with regard to oneself and others. The conclusion is that
      professional carers need to acknowledge the changing vulnerability of dependent
      older persons over time. The implication is a relational approach to autonomy
      beyond the traditional individualistic approach.

PMID- 23533744
TI  - Prevalence of oral habits in children with cleft lip and palate.
AB  - This study investigated the prevalence of oral habits in children with clefts
      aged three to six years, compared to a control group of children without clefts
      in the same age range, and compared the oral habits between children with clefts
      with and without palatal fistulae. The sample was composed of 110 children aged 3
      to 6 years with complete unilateral cleft lip and palate and 110 children without
      alterations. The prevalence of oral habits and the correlation between habits and
      presence of fistulae (for children with clefts) were analyzed by questionnaires
      applied to the children caretakers. The cleft influenced the prevalence of oral
      habits, with lower prevalence of pacifier sucking for children with cleft lip and
      palate and higher prevalence for all other habits, with significant association
      (P < 0.05). There was no significant association between oral habits and presence
      of fistulae (P > 0.05). The lower prevalence of pacifier sucking and higher
      prevalence of other oral habits agreed with the postoperative counseling to
      remove the pacifier sucking habit when the child is submitted to palatoplasty,
      possibly representing a substitution of habits. There was no causal relationship
      between habits and presence of palatal fistulae.

PMID- 23533745
TI  - Prevention and treatment of venous thromboembolism with new oral anticoagulants:
      a practical update for clinicians.
AB  - Traditional anticoagulants, such as warfarin and enoxaparin, have several
      limitations, including parenteral administration, need for laboratory monitoring,
      and ongoing dose adjustment, which may limit optimal patient care. Newer oral
      anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate)
      and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have
      been developed to overcome these drawbacks, and thereby improve patient care.
      Several of these agents have been approved for use in the prevention and
      treatment of venous and/or systemic thromboembolism. The objective of this paper
      is to provide an overview of the available clinical trial data for these new oral
      anticoagulants in the prevention and treatment of venous thromboembolism and a
      practical update for clinicians.

PMID- 23533746
TI  - The efficacy and safety of rivaroxaban for venous thromboembolism prophylaxis
      after total hip and total knee arthroplasty.
AB  - Venous thromboembolism (VTE) is a common complication after total hip and total
      knee arthroplasty. Currently used methods of VTE prophylaxis after these
      procedures have important limitations, including parenteral administration, and
      unpredictable plasma levels requiring frequent monitoring and dose adjustment
      leading to decreased patient compliance with recommended guidelines. New oral
      anticoagulants have been demonstrated in clinical trials to be equally
      efficacious to enoxaparin and allow for fixed dosing without the need for
      monitoring. Rivaroxaban is one of the new oral anticoagulants and is a direct
      factor Xa inhibitor that has demonstrated superior efficacy to that of
      enoxaparin. However, the data also suggest that rivaroxaban has an increased risk
      of bleeding compared to enoxaparin. This paper reviews the available data on the
      efficacy and safety of rivaroxaban for VTE prophylaxis after total hip and total
      knee arthroplasty.

PMID- 23533747
TI  - Active Case Finding of Pulmonary Tuberculosis through Screening of Respiratory
      Symptomatics Using Sputum Microscopy: Is It Time to Change the Paradigm?
AB  - Background. One of the main strategies for the early detection of pulmonary
      tuberculosis (PTB) is through the screening of individuals with symptoms
      compatible with PTB. Although this is programmatic strategy for active case
      finding, its yield is not well known. Objective. To determine the yield of
      pulmonary tuberculosis active case finding through the screening of respiratory
      symptomatic (RS) patients at a general hospital. Methods. RS patients were
      defined as subjects complaining of cough and/or sputum for a period of 2 or more
      weeks. Outpatients and their companions were approached while they waited in the
      outpatient care areas of the hospital to detect RS. Two samples from different
      days or 2 samples taken 2 hours apart on the same day were collected. Results.
      122 RS patients were identified. Fifty-seven patients (46.7%) had at least one
      sputum sample analyzed. Three patients presented a positive smear and 2 were
      culture positive; neither had upper airway symptoms. None of the patients with
      productive cough and upper airway symptoms had a positive smear (P = 0.07). Only
      19 (33.3%) returned to the laboratory to retrieve their results. Conclusion.
      Current strategy to screen RS patients based only on clinical data has a low
      compliance. Specific strategies to increase compliance (removal of barriers,
      incentives, etc.) should be implemented.

PMID- 23533748
TI  - Development of a danish language version of the manchester foot pain and
      disability index: reproducibility and construct validity testing.
AB  - Introduction. The Manchester Foot Pain and Disability Index (MFPDI) is a 19-item
      questionnaire for the assessment of disability caused by foot pain. The aim was
      to develop a Danish language version of the MFPDI (MFPDI-DK) and evaluate its
      reproducibility and construct validity. Methods. A Danish version was created,
      following a forward-backward translation procedure. A sample of 84 adult patients
      with foot pain was recruited. Participants completed two copies of the MFPDI-DK
      within a 24- to 48-hour interval, along with the Medical Outcomes Study Short
      Form 36 (SF-36), and a pain Visual Analog Scale (VAS). Reproducibility was
      assessed using the intraclass correlation coefficient (ICC) and 95% limits of
      agreement (Bland-Altman plot). Construct validity was evaluated with Pearson's
      Rho, using a priori hypothesized correlations with SF-36 subscales and VASmean.
      Results. The MFPDI-DK showed very good reliability with an ICC of 0.92 (0.88
      0.95). The 95% limits of agreement ranged from -6.03 to 6.03 points. Construct
      validity was supported by moderate to very strong correlations with the SF-36
      physical subscales and VASmean. Conclusion. The MFPDI-DK appears to be a valid
      and reproducible instrument in evaluating foot-pain-related disability in Danish
      adult patients in cross-sectional samples. Further research is needed to test the
      responsiveness of the MFPDI-DK.

PMID- 23533749
TI  - Effects of ROI Placement on PET-Based Assessment of Tumor Response to Therapy.
AB  - Purpose. Quantitative PET response assessment during therapy requires regions of
      interest (ROI). Commonly, a fixed-size ROI is placed at the maximum uptake point
      in the pretreatment study. For intratreatment, the ROI is placed either at the
      maximum uptake point (ROIpeak) or at the same location as the pretreatment ROI
      (ROIsame). We have evaluated the effects of the ROI placement on response
      assessment. Methods. PET scans of 15 head and neck cancer patients were used to
      evaluate the effects of the two ROI methods on response assessment. Results. The
      average intratreatment ROIpeak uptake was 13.4% higher than the ROIsame uptake
      (range -14% to 38%). The average relative change in ROIpeak uptake was 7.9% lower
      than ROIsame uptake (range -5% to 36%), resulting in ambiguous tumour
      classification in 19% of the tumours. Conclusion. Quantitative PET response
      assessment using a fixed-size ROI is sensitive the ROI placement. The difference
      between ROIpeak and ROIsame could be substantial resulting in ambiguous response
      assessment. Although the fixed-size ROI is simple to implement, it is also prone
      to the limitations and should be used with caution. Clinical trial data are
      necessary to establish reliable thresholds for fixed-size ROI techniques and to
      evaluate their efficacy for response assessment.

PMID- 23533750
TI  - Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG
      PET/CT.
AB  - Target definition is the largest source of geometric uncertainty in radiation
      therapy. This is partly due to a lack of contrast between tumor and healthy soft
      tissue for computed tomography (CT) and due to blurriness, lower spatial
      resolution, and lack of a truly quantitative unit for positron emission
      tomography (PET). First-, second-, and higher-order statistics, Tamura, and
      structural features were characterized for PET and CT images of lung carcinoma
      and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours
      (KNN) classifiers as nodes containing combinations of 3 features were trained and
      used for segmentation of the gross tumor volume. This approach was validated for
      31 patients from two separate institutions and scanners. The results were
      compared with thresholding approaches, the fuzzy clustering method, the 3-level
      fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm,
      and a single KNN using Hounsfield units and standard uptake value. The results
      showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest
      average Dice coefficient of 0.607, and a specificity of 99.2% for classifying
      voxels when using a probabilistic ground truth provided by simultaneous truth and
      performance level estimation using contours drawn by 3 trained physicians.

PMID- 23533751
TI  - The Relationship between Obstructive Sleep Apnea and Atrial Fibrillation: A
      Complex Interplay.
AB  - In recent years, growing evidence suggests an association between obstructive
      sleep apnea (OSA), a common sleep breathing disorder which is increasing in
      prevalence as the obesity epidemic surges, and atrial fibrillation (AF), the most
      common cardiac arrhythmia. AF is a costly public health problem increasing a
      patient's risk of stroke, heart failure, and all-cause mortality. It remains
      unclear whether the association is based on mutual risk factors, such as obesity
      and hypertension, or whether OSA is an independent risk factor and causative in
      nature. This paper explores the pathophysiology of OSA which may predispose to
      AF, clinical implications of stroke risk in this cohort who display overlapping
      disease processes, and targeted treatment strategies such as continuous positive
      airway pressure and AF ablation.

PMID- 23533752
TI  - Early infant exposure to excess multivitamin: a risk factor for autism?
AB  - Autism, a neurodevelopmental disorder that affects boys more than girls, is often
      associated with altered levels of monoamines (serotonin and catecholamines),
      especially elevated serotonin levels. The monoamines act as both
      neurotransmitters and signaling molecules in the gastrointestinal and immune
      systems. The evidence related to monoamine metabolism may be summarized as
      follows: (i) monoamine neurotransmitters are enzymatically degraded/inactivated
      by three mechanisms: oxidative deamination, methylation, and sulfation. The
      latter two are limited by the supply of methyl groups and sulfate, respectively.
      (ii) A decrease in methylation- and sulfation-mediated monoamine inactivation can
      be compensated by an increase in the oxidative deamination catalyzed by monoamine
      oxidase, an X-linked enzyme exhibiting higher activity in females than in males.
      (iii) Vitamins can, on one hand, facilitate the synthesis of monoamine
      neurotransmitters and, on the other hand, inhibit their inactivation by competing
      for methylation and sulfation. Therefore, we postulate that excess multivitamin
      feeding in early infancy, which has become very popular over the past few
      decades, may be a potential risk factor for disturbed monoamine metabolism. In
      this paper, we will focus on the relationship between excess multivitamin
      exposure and the inactivation/degradation of monoamine neurotransmitters and its
      possible role in the development of autism.

PMID- 23533753
TI  - Long-Term Effects of AposTherapy in Patients with Osteoarthritis of the Knee: A
      Two-Year Followup.
AB  - Several biomechanics treatments for knee osteoarthritis (OA) have emerged with
      the goal of reducing pain and improving function. Through this, researchers have
      hoped to achieve a transition from the pathological gait patterns to coordinated
      motor responses. The purpose of the study was to determine the long-term effects
      of a therapy using a biomechanical device in patients with knee OA. Patients with
      knee OA were enrolled to active and control groups. The biomechanical device used
      in therapy (AposTherapy) was individually calibrated to each patient in the
      active group. Patients in the control group received standard treatment. Outcomes
      were the Western Ontario and McMaster Osteoarthritis Index (WOMAC), Aggregated
      Locomotor Function (ALF), Short Form 36 (SF-36), and Knee Society Score
      assessments. The active and control groups were similar at the baseline (group
      difference in all scores P > 0.05). The active group showed a larger improvement
      over time between groups in all three WOMAC categories (F = 16.8, 21.7, and 18.1
      for pain, stiffness, and function; all P < 0.001), SF-36 Physical Scale (F = 5.8;
      P = 0.02), Knee Society Knee Score (F = 4.3; P = 0.044 ), and Knee Society
      Function Score (F = 6.5; P = 0.014 ). At the two-year endpoint, the active group
      showed significantly better results (all P <= 0.001). The groups showed a
      difference of 4.9, 5.6, and 4.7 for the WOMAC pain, stiffness, and function
      scores, respectively, 10.8 s in ALF score, 30.5 in SF-36 Physical Scale, 16.9 in
      SF-36 Mental Scale, 17.8 in Knee Society Knee Score, and 25.2 in Knee Society
      Function Score. The biomechanical therapy examined was shown to significantly
      reduce pain and improve function and quality of life of patients with knee OA
      over the long term.

PMID- 23533754
TI  - "Preventing the pain" when working with family and sexual violence in primary
      care.
AB  - Primary care professionals (PCPs) are increasingly being expected to identify and
      respond to family and sexual violence as the chronic nature and severity of the
      long-term health impacts are increasingly recognized. This discussion paper
      reports the authors' expert opinion from their experiences running international
      workshops to prevent trauma among those who work and research sexual violence. It
      describes the burnout and secondary traumatic stress literature which provides
      the evidence supporting their work. Implications for practicing basic training in
      response to trauma and ongoing education are a key area for responding to family
      violence and preventing professional stress. A professional culture that supports
      and values caring well for those who have experienced family violence as well as
      "caring for the carer" is needed. Working in teams and having more support
      systems in place are likely to protect PCPs from secondary traumatic stress and
      burnout. Undergraduate and postgraduate training of PCPs to develop trauma
      knowledge and the skills to ask about and respond to family violence safely are
      essential. In addition, the healthcare system, workplace, and the individual
      practitioner support structures need to be in place to enable PCPs to provide
      safe and effective long-term care and access to other appropriate services for
      those who have experienced family violence.

PMID- 23533755
TI  - Inhibition of NF- kappa B by Dehydroxymethylepoxyquinomicin Suppresses Invasion
      and Synergistically Potentiates Temozolomide and gamma -Radiation Cytotoxicity in
      Glioblastoma Cells.
AB  - Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ)
      and radiation, the overall survival of patients with glioblastoma (GBM) remains
      poor. Vast evidence has indicated that the nuclear factor NF- kappa B is
      constitutively activated in cancer cells, playing key roles in growth and
      survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a
      selective NF- kappa B inhibitor with antiproliferative properties in GBM. In the
      present study, the ability of DHMEQ to surmount tumor's invasive nature and
      therapy resistance were further explored. Corroborating results showed that DHMEQ
      impaired cell growth in dose- and time-dependent manners with G2/M arrest when
      compared with control. Clonogenicity was also significantly diminished with
      increased apoptosis, though necrotic cell death was also observed at comparable
      levels. Notably, migration and invasion were inhibited accordingly with lowered
      expression of invasion-related genes. Moreover, concurrent combination with TMZ
      synergistically inhibited cell growth in all cell lines, as determined by
      proliferation and caspase-3 activation assays, though in those that express O(6)
      methylguanine-DNA methyltransferase, the synergistic effects were schedule
      dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing
      radiation. Taken together, our results strengthen the potential usefulness of
      DHMEQ in future therapeutic strategies for tumors that do not respond to
      conventional approaches.

PMID- 23533756
TI  - Transplant outcomes in patients with idiopathic membranous nephropathy.
AB  - Background. The natural history of idiopathic membranous nephropathy and
      recurrent disease in transplants is variable. We performed a retrospective cohort
      study of renal transplant recipients with a primary diagnosis of idiopathic
      membranous nephropathy. We aimed to establish patterns of disease recurrence and
      to identify factors associated with disease recurrence. Methods. We accessed the
      Irish renal transplant database to identify patients with biopsy-proven
      idiopathic membranous nephropathy in receipt of a renal transplant between 1982
      and 2010. A detailed medical chart review was performed in all cases, and a
      senior renal histopathologist reviewed all histology specimens. Results. The
      outcomes of 32 patients, in receipt of 36 grafts, are reported. There was a male
      preponderance (n = 29). Significant graft dysfunction, directly attributable to
      recurrent disease, was evident in 31% of cases at 10 years. There was no
      significant association between time on dialysis, HLA mismatch, occurrence of
      rejection, and the development of recurrent membranous disease. One patient was
      retransplanted twice; all three grafts were lost to aggressive recurrent
      membranous disease. Conclusions. It remains difficult to identify those that will
      develop recurrent membranous nephropathy. Almost one third of patients in this
      cohort developed clinically significant recurrent disease at 10 years.

PMID- 23533757
TI  - Current status and advances in quantitative proteomic mass spectrometry.
AB  - The accurate quantitation of proteins and peptides in complex biological systems
      is one of the most challenging areas of proteomics. Mass spectrometry-based
      approaches have forged significant in-roads allowing accurate and sensitive
      quantitation and the ability to multiplex vastly complex samples through the
      application of robust bioinformatic tools. These relative and absolute
      quantitative measures using label-free, tags, or stable isotope labelling have
      their own strengths and limitations. The continuous development of these methods
      is vital for increasing reproducibility in the rapidly expanding application of
      quantitative proteomics in biomarker discovery and validation. This paper
      provides a critical overview of the primary mass spectrometry-based quantitative
      approaches and the current status of quantitative proteomics in biomedical
      research.

PMID- 23533758
TI  - Measuring the quality of life in patients with multiple sclerosis in clinical
      practice: a necessary challenge.
AB  - While the physical disability aspect of multiple sclerosis (MS) is of great
      importance, quality of life (QoL) measurements are being considered increasingly
      important with regard to evaluating disease progression, treatment, and the
      management of care provided to MS patients. Despite the acknowledged need to
      consider QoL issues, QoL assessment remains underutilized in clinical practice.
      These issues should be explored and understood to promote the use of measuring
      QoL in MS clinical practice. We explore the difficulties for clinicians: choosing
      and determining the most appropriate QoL measure and how to best integrate QoL
      measurements into clinical practice. This paper discusses several avenues to
      provide to clinicians arguments of the clinical relevance and accuracy of QoL
      instruments and ultimately to enhance the use of QoL measures in clinical
      practice for MS patients.

PMID- 23533759
TI  - Gait variability and multiple sclerosis.
AB  - Gait variability, that is, fluctuations in movement during walking, is an
      indicator of walking function and has been associated with various adverse
      outcomes such as falls. In this paper, current research concerning gait
      variability in persons with multiple sclerosis (MS) is discussed. It is well
      established that persons with MS have greater gait variability compared to age
      and gender matched controls without MS. The reasons for the increase in gait
      variability are not completely understood. Evidence indicates that disability
      level, assistive device use, attentional requirement, and fatigue are related to
      gait variability in persons with MS. Future research should address the time
      evolving structure (i.e., temporal characteristics) of gait variability, the
      clinical importance of gait variability, and underlying mechanisms that drive
      gait variability in individuals with MS.

PMID- 23533761
TI  - Maternal body mass index does not affect neonatal umbilical artery blood gas
      parameters.
AB  - This study was undertaken to assess the impact of obesity on fetal well-being in
      glucose-tolerant and nonhypertensive women. Medical charts of all patients
      admitted to the labor and delivery department at our institution between January,
      2011 and July, 2011 were retrospectively reviewed. Patients with
      diabetes/impaired glucose tolerance or hypertension were excluded. A total of 100
      women, 50 lean and 50 obese, were included. Umbilical artery blood gas parameters
      (BGPs) were compared in lean (<25 kg/m(2)) and obese (>= 30 kg/m(2)) women. Obese
      and lean women were comparable with respect to all baseline characteristics.
      There was no difference in any of the BGP or Apgar scores between obese and lean
      patients. Pearson's correlation coefficient found no significant correlation
      between BMI and BGP/Apgar scores. Maternal obesity does not seem to affect BGP
      and fetal well-being in glucose-tolerant and nonhypertensive women.

PMID- 23533760
TI  - The consequences of chorioamnionitis: preterm birth and effects on development.
AB  - Preterm birth is a major cause of perinatal mortality and long-term morbidity.
      Chorioamnionitis is a common cause of preterm birth. Clinical chorioamnionitis,
      characterised by maternal fever, leukocytosis, tachycardia, uterine tenderness,
      and preterm rupture of membranes, is less common than subclinical/histologic
      chorioamnionitis, which is asymptomatic and defined by inflammation of the
      chorion, amnion, and placenta. Chorioamnionitis is often associated with a fetal
      inflammatory response. The fetal inflammatory response syndrome (FIRS) is defined
      by increased systemic inflammatory cytokine concentrations, funisitis, and fetal
      vasculitis. Clinical and epidemiological studies have demonstrated that FIRS
      leads to poor cardiorespiratory, neurological, and renal outcomes. These
      observations are further supported by experimental studies that have improved our
      understanding of the mechanisms responsible for these outcomes. This paper
      outlines clinical and experimental studies that have improved our current
      understanding of the mechanisms responsible for chorioamnionitis-induced preterm
      birth and explores the cellular and physiological mechanisms underlying poor
      cardiorespiratory, neural, retinal, and renal outcomes observed in preterm
      infants exposed to chorioamnionitis.

PMID- 23533762
TI  - Limiting excess weight gain in healthy pregnant women: importance of energy
      intakes, physical activity, and adherence to gestational weight gain guidelines.
AB  - Few studies have investigated if compliance with energy intakes, physical
      activity, and weight gain guidelines attenuate postpartum weight retention (PPWR)
      in mothers attending prenatal classes. We investigated whether (a) daily energy
      intakes within 300 kcal of estimated energy requirements (EERs), (b) walking more
      than 5000 steps/day, (c) targeting the recommended weight gain goals for
      prepregnancy BMI, and/or (d) achieving weekly or total gestational weight gain
      (GWG) recommendations minimized PPWR in 54 women attending prenatal classes in
      Montreal/Ottawa, Canada. Participants completed a validated pregnancy physical
      activity questionnaire (PPAQ), 3 telephone-validated 24-hr dietary recalls, and
      wore a pedometer for one week. PPWR was measured 6 weeks after delivery. Results
      showed that 72% had healthy prepregnancy BMIs. However, 52% consumed >300
      kcal/day in excess of their EER, 54% exceeded recommended GWG, and more
      overweight (93%) than normal weight women (38%) cited nonrecommended GWG targets.
      Following delivery, 33% were classified as overweight, and 17% were obese.
      Multiple logistic regressions revealed that women targeting "recommended weight
      gain advice" were 3 times more likely to meet total GWG recommendations (OR: 3.2,
      P < 0.05); women who complied with weekly GWG goals minimized PPWR (OR: 4.2, P <
      0.02). In conclusion, appropriate GWG targets, lower energy intakes, and physical
      activity should be emphasized in prenatal education programs.

PMID- 23533763
TI  - Gene expression of adhesion molecules in endothelial cells from patients with
      peripheral arterial disease is reduced after surgical revascularization and
      pharmacological treatment.
AB  - Atherosclerosis is an inflammatory disease characterized by immunological
      activity, in which endothelial dysfunction represents an early event leading to
      subsequent inflammatory vascular damage. We investigated gene expression of the
      adhesion molecules (AMs) ICAM-1, VCAM-1, and beta1-integrin in endothelial cells
      (ECs) isolated from venous blood (circulating EC, cEC) and purified from femoral
      plaques (pEC) obtained from 9 patients with peripheral artery disease (PAD)
      submitted to femoral artery thrombendarterectomy (FEA). In addition, in
      peripheral blood mononuclear cells (PBMCs) of the same subjects, we investigated
      gene expression of IFN-gamma, IL-4, TGF-beta, and IL-10. Patients were
      longitudinally evaluated 1 month before surgery, when statin treatment was
      established, at the time of surgery, and after 2 and 5 months. All AM mRNA
      levels, measured by means of real-time PCR, in cEC diminished during the study,
      up to 41-50% of initial levels at followup. AM mRNA expression was significantly
      higher in pEC than in cEC. During the study, in PBMCs, TGF-beta and IL-10 mRNA
      levels remained unchanged while IFN-gamma and IL-4 levels increased; however, the
      ratio IFN-gamma/IL-4 showed no significant modification. In PAD patients, FEA and
      statin treatment induce a profound reduction of AM expression in cEC and affect
      cytokine mRNA expression in PBMCs.

PMID- 23533764
TI  - Improving knowledge and process for international emergency medicine fellowship
      applicants: a call for a uniform application.
AB  - Background. There are currently 34 International Emergency Medicine (IEM)
      fellowship programs. Applicants and programs are increasing in number and
      diversity. Without a standardized application, applicants have a difficulty
      approaching programs in an informed and an organized method; a streamlined
      application system is necessary. Objectives. To measure fellows' knowledge of
      their programs' curricula prior to starting fellowship and to determine what
      percent of fellows and program directors would support a universal application
      system. Methods. A focus group of program directors, recent, and current fellows
      convened to determine the most important features of an IEM fellowship
      application process. A survey was administered electronically to a convenience
      sample of 78 participants from 34 programs. Respondents included fellowship
      directors, fellows, and recent graduates. Results. Most fellows (70%) did not
      know their program's curriculum prior to starting fellowship. The majority of
      program directors and fellows support a uniform application service (81% and 67%,
      resp.) and deadline (85% for both). A minority of program directors (35%) and
      fellows (30%) support a formal match. Conclusions. Program directors and fellows
      support a uniform application service and deadline, but not a formalized match.
      Forums for disseminating IEM fellowship information and for administering a
      uniform application service and deadline are currently in development to improve
      the process.

PMID- 23533765
TI  - The NT-ProBNP Test in Subjects with End-Stage Renal Disease on Hemodialysis
      Presenting with Acute Dyspnea: Is Knowing Worth the Cost?
AB  - Background. The NT-ProBNP/BNP test has been validated as a marker for determining
      the etiology of acute dyspnea. In the setting of end-stage renal disease on
      hemodialysis (ESRD on HD), the utility of the NT-ProBNP/BNP test has not been
      validated. This study examines the clinical utility of the NT-ProBNP test in the
      setting of ESRD on HD patients presenting with acute dyspnea. Methods. A
      retrospective case series of 250 subjects were admitted to Cooper University
      Hospital, 07/2010-03/2011, with ESRD and HD presenting with dyspnea. The
      incidences of echocardiography, cardiology consultation, and NT-ProBNP elevated
      and normal were examined. Correlation coefficients were calculated for NT-ProBNP
      with age (years), estimated dry weight (kg), amount of fluid removed (L), and
      ejection fraction (EF in %) among other echocardiography parameters. Results. Of
      the total sample 235 patients had NT-ProBNP levels performed. Cardiology consults
      were placed in 68.8% and 58% who underwent echocardiography. Of those for whom an
      echocardiography was performed estimated mean EFs of 54.6%, 50.8%, and 61.7% were
      observed among the NT-ProBNP elevated group, normal group, and no NT-ProBNP
      group, respectively. No differences were detected in all other echocardiography
      measurements. No correlation was observed between NT-ProBNP and age (r = 0.05),
      baseline EDW (r = -0.09), amount of fluid removed (r = 0.07), or EF (r = 0.02).
      Conclusion. In the setting of ESRD on HD, the NT-ProBNP test has no clinical
      utility in determining the etiology of acute dyspnea. This can be demonstrated
      through echocardiographic and therapeutic parameters measured in this study.

PMID- 23533766
TI  - Latest approved therapies for metastatic melanoma: what comes next?
AB  - Nowadays, oncogene-directed therapy and immunotherapy represent the two most
      promising avenues for patients with metastatic melanoma. The recent oncogene
      directed therapeutic, vemurafenib, usually produces high level of tumor shrinkage
      and survival benefits in many patients with B-RAF (V600E) mutant melanomas,
      although the fast and high degrees of responses are likely short-lived.
      Conversely, the newly-approved immunotherapeutic, ipilimumab, produces durable
      responses in patients presenting CTLA-4 T-cell surface protein. Nevertheless, the
      possible synergy in combining these two therapeutic strategies primarily rely on
      the rational design of medical protocols (e.g., sequence and timing of agent
      administration; drug selectivity; compatibility of combined therapies i.e.,
      adoptive T cell or agents, i.e., MEK inhibitor trametinib, PD-1 and PDL-1
      blockers). Improved therapeutic protocols shall overcome therapeutic limitations
      such as the (i) tolerability and safety (i.e., minimal toxic side-effects); (ii)
      progression free survival (e.g., reduced relapse disease frequency); (iii)
      duration response (i.e., decreased drug resistance). Eventually,
      multidisciplinary approaches are still requested (e.g., genomics for personalized
      medicine, nanomedicine to overcome low free-drug bioavailability and targeting,
      systematic search of "melanoma stem cells" to enhance the prognosis and develop
      more valuable theranostics). In this paper, I will mainly present and discuss the
      latest and promising treatments for advanced cutaneous melanomas.

PMID- 23533767
TI  - Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through
      HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite
      Nanoparticles.
AB  - Exploitation of biological properties unique to cancer cells may provide a novel
      approach to overcome difficult challenges to the treatment of advanced melanoma.
      In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis
      substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of
      tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from
      melanogenesis substrates, which are expected to be selectively incorporated into
      melanoma cells and produce highly reactive free radicals through reacting with
      tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by
      oxidative stress and apoptotic cell death. Magnetite nanoparticles were
      conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic
      effects through nonapoptotic cell death and generation of heat shock protein
      (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic
      processes, NPrCAP was also expected to provide melanoma-targeted drug delivery
      system.

PMID- 23533768
TI  - Adenoviral Delivery of the VEGF and BMP-6 Genes to Rat Mesenchymal Stem Cells
      Potentiates Osteogenesis.
AB  - The combined delivery of mesenchymal stem cells (MSCs), vascular endothelial
      growth factor (VEGF), and bone morphogenetic protein (BMP) to sites of bone
      injury results in enhanced repair compared to the administration of a single
      factor or a combination of two factors. Based on these findings, we hypothesized
      that coexpression of VEGF and BMP-6 genes would enhance the osteoblastic
      differentiation of rat bone-marrow-derived stem cells (rMSCs) and osteogenesis by
      comparison to rMSCs that do not express VEGF and BMP-6. We prepared a GFP tagged
      adenovirus vector (Ad-VEGF+BMP-6) that contained DNA encoding the hVEGF and hBMP
      6 genes. rMSCs were transduced with the virus, and the successful transduction
      was confirmed by green fluorescence and by production of VEGF and BMP-6 proteins.
      The cells were cultured to assess osteoblastic differentiation or administered in
      the Fischer 344 rats to assess bone formation. Mineralization of rMSCs transduced
      with Ad-VEGF+BMP-6 was significantly enhanced over the nontransduced rMSCs. Only
      transduced rMSCs could induce osteogenesis in vivo, whereas Ad-VEGF+BMP-6 or
      nontransduced rMSCs alone did not induce osteogenesis. The data suggests that the
      combined delivery of MSCs, VEGF, and BMP-6 is an attractive option for bone
      repair therapy.

PMID- 23533769
TI  - Stealth properties to improve therapeutic efficacy of drug nanocarriers.
AB  - Over the last few decades, nanocarriers for drug delivery have emerged as
      powerful tools with unquestionable potential to improve the therapeutic efficacy
      of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to
      ameliorate the site specificity of drug action and reduce the systemic side
      effects. By virtue of their small size they can be injected intravenously and
      disposed into the target tissues where they release the drug. Nanocarriers
      interact massively with the surrounding environment, namely, endothelium vessels
      as well as cells and blood proteins. Consequently, they are rapidly removed from
      the circulation mostly by the mononuclear phagocyte system. In order to endow
      nanosystems with long circulation properties, new technologies aimed at the
      surface modification of their physicochemical features have been developed. In
      particular, stealth nanocarriers can be obtained by polymeric coating. In this
      paper, the basic concept underlining the "stealth" properties of drug
      nanocarriers, the parameters influencing the polymer coating performance in terms
      of opsonins/macrophages interaction with the colloid surface, the most commonly
      used materials for the coating process and the outcomes of this peculiar
      procedure are thoroughly discussed.

PMID- 23533770
TI  - Cancer epigenetics: new therapies and new challenges.
AB  - Cancer is nowadays considered to be both a genetic and an epigenetic disease. The
      most well studied epigenetic modification in humans is DNA methylation; however
      it becomes increasingly acknowledged that DNA methylation does not work alone,
      but rather is linked to other modifications, such as histone modifications.
      Epigenetic abnormalities are reversible and as a result novel therapies that work
      by reversing epigenetic effects are being increasingly explored. The biggest
      clinical impact of epigenetic modifying agents in neoplastic disorders thus far
      has been in haematological malignancies, and the efficacy of DNMT inhibitors and
      HDAC inhibitors in blood cancers clearly attests to the principle that
      therapeutic modification of the cancer cell epigenome can produce clinical
      benefit. This paper will discuss the most well studied epigenetic modifications
      and how these are linked to cancer, will give a brief overview of the clinical
      use of epigenetics as biomarkers, and will focus in more detail on epigenetic
      drugs and their use in solid and blood cancers.

PMID- 23533771
TI  - Bisphosphonates and cancer: what opportunities from nanotechnology?
AB  - Bisphosphonates (BPs) are synthetic analogues of naturally occurring
      pyrophosphate compounds. They are used in clinical practice to inhibit bone
      resorption in bone metastases, osteoporosis, and Paget's disease. BPs induce
      apoptosis because they can be metabolically incorporated into nonhydrolyzable
      analogues of adenosine triphosphate. In addition, the nitrogen-containing BPs (N
      BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP)
      synthase, a key enzyme of the mevalonate pathway. These molecules are able to
      induce apoptosis of a number of cancer cells in vitro. Moreover, antiangiogenic
      effect of BPs has also been reported. However, despite these promising
      properties, BPs rapidly accumulate into the bone, thus hampering their use to
      treat extraskeletal tumors. Nanotechnologies can represent an opportunity to
      limit BP accumulation into the bone, thus increasing drug level in extraskeletal
      sites of the body. Thus, nanocarriers encapsulating BPs can be used to target
      macrophages, to reduce angiogenesis, and to directly kill cancer cell. Moreover,
      nanocarriers can be conjugated with BPs to specifically deliver anticancer agent
      to bone tumors. This paper describes, in the first part, the state-of-art on the
      BPs, and, in the following part, the main studies in which nanotechnologies have
      been proposed to investigate new indications for BPs in cancer therapy.

PMID- 23533773
TI  - Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells.
AB  - Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that exists in
      living systems, and it is a major component of the extracellular matrix. The
      hyaluronic acid receptor CD44 is found at low levels on the surface of
      epithelial, haematopoietic, and neuronal cells and is overexpressed in many
      cancer cells particularly in tumour initiating cells. HA has been therefore used
      as ligand attached to HA-lipid-based nanovectors for the active targeting of
      small or large active molecules for the treatment of cancer. This paper describes
      the different approaches employed for the preparation, characterization, and
      evaluation of these potent delivery systems.

PMID- 23533774
TI  - Production of Pseudomonas aeruginosa Intercellular Small Signaling Molecules in
      Human Burn Wounds.
AB  - Pseudomonas aeruginosa has developed a complex cell-to-cell communication system
      that relies on low-molecular weight excreted molecules to control the production
      of its virulence factors. We previously characterized the transcriptional
      regulator MvfR, that controls a major network of acute virulence functions in P.
      aeruginosa through the control of its ligands, the 4-hydroxy-2-alkylquinolines
      (HAQs)-4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline
      (PQS). Though HHQ and PQS are produced in infected animals, their ratios differ
      from those in bacterial cultures. Because these molecules are critical for the
      potency of activation of acute virulence functions, here we investigated whether
      they are also produced during human P. aeruginosa acute wound infection and
      whether their ratio is similar to that observed in P. aeruginosa-infected mice.
      We found that a clinically relevant P. aeruginosa isolate produced detectable
      levels of HAQs with ratios of HHQ and PQS that were similar to those produced in
      burned and infected animals, and not resembling ratios in bacterial cultures.
      These molecules could be isolated from wound tissue as well as from drainage
      liquid. These results demonstrate for the first time that HAQs can be isolated
      and quantified from acute human wound infection sites and validate the relevance
      of previous studies conducted in mammalian models of infection.

PMID- 23533775
TI  - Harnessing DNA synthesis to develop rapid responses to emerging and pandemic
      pathogens.
AB  - Given the interconnected nature of our world today, emerging pathogens and
      pandemic outbreaks are an ever-growing threat to the health and economic
      stability of the global community. This is evident by the recent 2009 Influenza A
      (H1N1) pandemic, the SARS outbreak, as well as the ever-present threat of global
      bioterrorism. Fortunately, the biomedical community has been able to rapidly
      generate sequence data so these pathogens can be readily identified. To date,
      however, the utilization of this sequence data to rapidly produce relevant
      experimental results or actionable treatments is lagging in spite of obtained
      sequence data. Thus, a pathogenic threat that has emerged and/or developed into a
      pandemic can be rapidly identified; however, translating this identification into
      a targeted therapeutic or treatment that is rapidly available has not yet
      materialized. This commentary suggests that the growing technology of DNA
      synthesis should be fully implemented as a means to rapidly generate in vivo data
      and possibly actionable therapeutics soon after sequence data becomes available.

PMID- 23533777
TI  - Hypofractionated external-beam radiotherapy for prostate cancer.
AB  - There are radiobiological rationales supporting hypofractionated radiotherapy for
      prostate cancer. The recent advancements in treatment planning and delivery allow
      sophisticated radiation treatments to take advantage of the differences in
      radiobiology of prostate cancer and the surrounding normal tissues. The
      preliminary results from clinical studies indicate that abbreviated fractionation
      programs can result in successful treatment of localized prostate cancer without
      escalation of late toxicity.

PMID- 23533778
TI  - Urologic characteristics and sexual behaviors associated with prostate cancer in
      an african-Caribbean population in barbados, west indies.
AB  - Prostate cancer (PC) is the principal malignancy affecting African descent men in
      the Caribbean and the USA. Disparities in incidence, prevalence, and mortality in
      these populations are poorly understood. We evaluated the urologic
      characteristics and sexual behaviors of men with histologically confirmed PC
      (cases) and age-matched controls in the nationwide Prostate Cancer in a Black
      Population (PCBP) study conducted in Barbados. Cases were around 1.5 to 3 times
      more likely to report symptoms of prostatic enlargement, hematuria/hematospermia,
      and previous prostatitis. Sexually transmitted infections (STIs) were similar
      among cases (24.5%) and controls (26.7%). First sexual intercourse before the age
      of 16 was associated with an increased likelihood of both low- (Gleason score <
      7; OR 1.63; 95% CI: 1.03-1.66) and high-grade PC (Gleason score >= 7; OR 1.82;
      1.11-2.99). PC risk decreased with later age of sexual debut (P-trend = 0.004).
      More lifetime sexual partners was associated with increased odds of high grade PC
      (P-trend = 0.02). The contribution of sexual behaviors to the development and the
      outcomes of PC is likely due to multiple mechanisms, and further study will be
      necessary to elucidate the underlying pathophysiologic mechanisms in this and
      similar populations.

PMID- 23533772
TI  - Recent trends in multifunctional liposomal nanocarriers for enhanced tumor
      targeting.
AB  - Liposomes are delivery systems that have been used to formulate a vast variety of
      therapeutic and imaging agents for the past several decades. They have
      significant advantages over their free forms in terms of pharmacokinetics,
      sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial
      nature of cancer and the complex physiology of the tumor microenvironment require
      the development of multifunctional nanocarriers. Multifunctional liposomal
      nanocarriers should combine long blood circulation to improve pharmacokinetics of
      the loaded agent and selective distribution to the tumor lesion relative to
      healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from
      blood at the tumor's vicinity, internalization motifs to move from tumor bounds
      and/or tumor intercellular space to the cytoplasm of cancer cells for effective
      tumor cell killing. This review will focus on current strategies used for cancer
      detection and therapy using liposomes with special attention to combination
      therapies.

PMID- 23533779
TI  - Analysis of preoperative detection for apex prostate cancer by transrectal
      biopsy.
AB  - Background. The aim of this study was to determine concordance rates for
      prostatectomy specimens and transrectal needle biopsy samples in various areas of
      the prostate in order to assess diagnostic accuracy of the transrectal biopsy
      approach, especially for presurgical detection of cancer in the prostatic apex.
      Materials and Methods. From 2006 to 2011, 158 patients whose radical
      prostatectomy specimens had been evaluated were retrospectively enrolled in this
      study. Concordance rates for histopathology results of prostatectomy specimens
      and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle,
      base, and transitional zones bilaterally) from 73 patients diagnosed at this
      institution, besides factors for detecting apex cancer in total 118 true positive
      and false negative apex cancers. Results. Prostate cancer was found most
      frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153
      (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No
      readily available preoperative factors for detecting apex cancer were identified.
      Conclusions. In Japanese patients, the most frequent location of prostate cancer
      is in the apex. There is a high false negative rate for transrectal biopsy
      samples. To improve the detection rate, transperitoneal biopsy or more accurate
      imaging technology is needed.

PMID- 23533776
TI  - Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma
      gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological
      Disorders.
AB  - Toxoplasma gondii is not only implicated in schizophrenia and related disorders,
      but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and
      autoimmune disorders. During its life cycle, the pathogen interacts with ~3000
      host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's
      disease, schizophrenia, bipolar disorder, depression, childhood obesity,
      Parkinson's disease, attention deficit hyperactivity disorder (P  from  8.01E -
      05  (ADHD)  to  1.22E - 71) (multiple sclerosis), and autism (P = 0.013), but not
      anorexia or chronic fatigue are highly enriched in the human arm of this
      interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it.
      The signalling pathways involved in the susceptibility gene/interactome overlaps
      are relatively specific and relevant to each disease suggesting a means whereby
      susceptibility genes could orient the attentions of a single pathogen towards
      disruption of the specific pathways that together contribute (positively or
      negatively) to the endophenotypes of different diseases. Conditional protein
      knockdown, orchestrated by T. gondii proteins or antibodies binding to those of
      the host (pathogen derived autoimmunity) and metabolite exchange, may contribute
      to this disruption. Susceptibility genes may thus be related to the causes and
      influencers of disease, rather than (and as well as) to the disease itself.

PMID- 23533780
TI  - Production of Enzymes from Agroindustrial Wastes by Biosurfactant-Producing
      Strains of Bacillus subtilis.
AB  - Bacteria in the genus Bacillus are the source of several enzymes of current
      industrial interest. Hydrolases, such as amylases, proteases, and lipases, are
      the main enzymes consumed worldwide and have applications in a wide range of
      products and industrial processes. Fermentation processes by Bacillus subtilis
      using cassava wastewater as a substrate are reported in the technical literature;
      however, the same combination of microorganisms and this culture medium is
      limited or nonexistent. In this paper, the amylase, protease, and lipase
      production of ten Bacillus subtilis strains previously identified as
      biosurfactant producers in cassava wastewater was evaluated. The LB1a and LB5a
      strains were selected for analysis using a synthetic medium and cassava
      wastewater and were identified as good enzyme producers, especially of amylases
      and proteases. In addition, the enzymatic activity results indicate that cassava
      wastewater was better than the synthetic medium for the induction of these
      enzymes.

PMID- 23533781
TI  - Statistical Analysis of Metal Chelating Activity of Centella asiatica and
      Erythroxylum cuneatum Using Response Surface Methodology.
AB  - The purpose of the study is to evaluate the relationship between the extraction
      parameters and the metal chelating activity of Centella asiatica (CA) and
      Erythroxylum cuneatum (EC). The response surface methodology was used to optimize
      the extraction parameters of methanolic extract of CA and EC with respect to the
      metal chelating activity. For CA, Run 17 gave optimum chelating activity with
      IC50 = 0.93 mg/mL at an extraction temperature of 25 degrees C, speed of
      agitation at 200 rpm, ratio of plant material to solvent at 1 g : 45 mL and
      extraction time at 1.5 hour. As for EC, Run 13 with 60 degrees C, 200 rpm, 1 g :
      35 mL and 1 hour had metal chelating activity at IC50 = 0.3817 mg/mL. Both
      optimized extracts were further partitioned using a solvent system to evaluate
      the fraction responsible for the chelating activity of the plants. The hexane
      fraction of CA showed potential activity with chelating activity at IC50 = 0.090
      and the ethyl acetate fraction of EC had IC50 = 0.120 mg/mL. The study showed
      that the response surface methodology helped to reduce the extraction time,
      temperature and agitation and subsequently improve the chelating activity of the
      plants in comparison to the conventional method.

PMID- 23533782
TI  - Antioxidant and Hepatoprotective Properties of Tofu (Curdle Soymilk) against
      Acetaminophen-Induced Liver Damage in Rats.
AB  - The antioxidant and hepatoprotective properties of tofu using acetaminophen to
      induce liver damage in albino rats were evaluated. Tofus were prepared using
      calcium chloride, alum, and steep water as coagulants. The polyphenols of tofu
      were extracted and their antioxidant properties were determined. The weight gain
      and feed intake of the rats were measured. The analysis of serum alanine
      aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase
      (AST), and lactate dehydrogenase (LDH) activities and the concentrations of
      albumin, total protein, cholesterol, and bilirubin were analyzed. The result
      reveals that the antioxidant property of both soluble and bound polyphenolic
      extracts was significantly higher in all tofus, but the steep water coagulated
      tofu was recorded higher. Rats fed with various tofus and acetaminophen had their
      serum ALP, ALT, AST, and LDH activities; total cholesterol; and bilirubin levels
      significantly (P < 0.05) reduced, and total protein and albumin concentrations
      increased when compared with basal diet and acetaminophen administered group.
      Therefore, all tofus curdled with various coagulants could be used to prevent
      liver damage caused by oxidative stress.

PMID- 23533783
TI  - Family-specific degenerate primer design: a tool to design consensus degenerated
      oligonucleotides.
AB  - Designing degenerate PCR primers for templates of unknown nucleotide sequence may
      be a very difficult task. In this paper, we present a new method to design
      degenerate primers, implemented in family-specific degenerate primer design (FAS
      DPD) computer software, for which the starting point is a multiple alignment of
      related amino acids or nucleotide sequences. To assess their efficiency, four
      different genome collections were used, covering a wide range of genomic lengths:
      Arenavirus (10 * 10(4) nucleotides), Baculovirus (0.9 * 10(5) to 1.8 * 10(5) bp),
      Lactobacillus sp. (1 * 10(6) to 2 * 10(6) bp), and Pseudomonas sp. (4 * 10(6) to
      7 * 10(6) bp). In each case, FAS-DPD designed primers were tested computationally
      to measure specificity. Designed primers for Arenavirus and Baculovirus were
      tested experimentally. The method presented here is useful for designing
      degenerate primers on collections of related protein sequences, allowing
      detection of new family members.

PMID- 23533784
TI  - Cytogenetic Characteristics of New Monosomic Stocks of Cotton (Gossypium hirsutum
      L.).
AB  - The use of aneuploid lines significantly increases the effectiveness of molecular
      genetic analysis and the development of superior quality breeding lines via
      substitutions by alien chromosomes. To date, however, a complete set of aneuploid
      series for each cotton chromosome is not available. Here, we present the
      development of a monosomic stock collection of cotton (Gossypium hirsutum L.)
      from Uzbekistan, including the origin of 92 primary monosomics, meiotic metaphase
      I analysis, study of tetrads of microspores, pollen fertility, and monosomic
      transmission rates for some monosomic lines. We report desynaptic effects of some
      monosomes detected both in parental and daughter monosomics, a positive role of
      interchanges in translocation heterozygous monosomics due to selective advantages
      of gametes with deficiency and a simultaneous interchange, pollen fertility
      variation, and strong differences in transmission rates. This monosomic cotton
      collection, developed using single genome background, will be useful for future
      breeding, genetic, cytogenetic, and molecular-genetic investigations of the
      cotton genome.

PMID- 23533786
TI  - A Reappraisal of Chemotherapy-Induced Liver Injury in Colorectal Liver Metastases
      before the Era of Antiangiogenics.
AB  - Background and Aims. Chemotherapy of colorectal liver metastases can induce
      hepatotoxicity in noncancerous liver. We describe these lesions and assess risk
      factors and impacts on postresection morbidity and mortality in naive patients to
      chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue
      lesions were analysed according to tumour, chemotherapy, surgery, and patient
      characteristics. Results. Fifty patients aged 62 +/- 9.3 years were included
      between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox
      (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity
      consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal
      fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative
      hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%)
      surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, P =
      0.04), especially LV5FU2 (P = 0.02). SD was associated with oxaliplatin (54.5%
      versus 23.5%, P = 0.05) and low body mass index (P = 0.003). NRH was associated
      with oxaliplatin (P = 0.03) and extensive resection (P = 0.04). No impact on
      mortality and morbidity was observed, apart postoperative elevation of bilirubin
      levels in case of PSF (P = 0.03), longer hospitalization in case of surgical
      hepatitis (P = 0.03), and greater blood loss in case of portal fibrosis (P =
      0.03). Conclusions. Chemotherapy of colorectal liver metastases induces
      sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related
      to 5FU, without any impact on postoperative mortality.

PMID- 23533785
TI  - Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder
      caused by homozygous expansion of a GAA.TTC trinucleotide repeat within the first
      intron of the FXN gene, leading to reduced FXN transcription and decreased levels
      of frataxin protein. Recent advances in FRDA research have revealed the presence
      of several epigenetic modifications that are either directly or indirectly
      involved in this FXN gene silencing. Although epigenetic marks may be inherited
      from one generation to the next, modifications of DNA and histones can be
      reversed, indicating that they are suitable targets for epigenetic-based therapy.
      Unlike other trinucleotide repeat disorders, such as Huntington disease, the
      large expansions of GAA.TTC repeats in FRDA do not produce a change in the
      frataxin amino acid sequence, but they produce reduced levels of normal frataxin.
      Therefore, transcriptional reactivation of the FXN gene provides a good
      therapeutic option. The present paper will initially focus on the epigenetic
      changes seen in FRDA patients and their role in the silencing of FXN gene and
      will be concluded by considering the potential epigenetic therapies.

PMID- 23533787
TI  - Histological and immunohistochemical revision of hepatocellular adenomas: a
      learning experience.
AB  - Light has been shed on the genotype/phenotype correlation in hepatocellular
      adenoma (HCA) recognizing HNF1 alpha -inactivated HCA (H-HCA), inflammatory HCA
      (IHCA), and beta -catenin-activated HCA (b-HCA). We reviewed retrospectively our
      surgical HCA series to learn how to recognize the different subtypes
      histopathologically and how to interpret adequately their immunohistochemical
      staining. From January 1992 to January 2012, 37 patients underwent surgical
      resection for HCA in our institution. Nine had H-HCA (25%) characterized by
      steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or
      SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient
      had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and beta -catenin
      nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two
      cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA
      histological and immunohistochemical characteristics suggesting a subgroup of
      beta -catenin-activated/HNF1 alpha -inactivated HCA, another b-HCA exhibited the
      IHCA histological and immunohistochemical characteristics suggesting a subgroup
      of beta -catenin-activated/inflammatory HCA. Interestingly, three patients had
      underlying vascular abnormalities. Using the recently published criteria enabled
      us to classify histopathologically our retrospective HCA surgical series with
      accurate recognition of b-HCA for which we confirm the higher risk of malignant
      transformation. We also underlined the association between HCA and vascular
      abnormalities.

PMID- 23533788
TI  - Outcome and structural integrity of rotator cuff after arthroscopic treatment of
      large and massive tears with double row technique: a 2-year followup.
AB  - Purpose. The purpose of this study was to evaluate the functional outcome and the
      tendon healing after arthroscopic double row rotator cuff repair of large and
      massive rotator cuff tears. Methods. 82 patients with a full-thickness large and
      massive rotator cuff tear underwent arthroscopic repair with double row
      technique. Results were evaluated by use of the UCLA, ASES, and Constant
      questionnaires, the Shoulder Strength Index (SSI), and range of motion. Follow-up
      time was 2 years. Magnetic resonance imaging (MRI) studies were performed on each
      shoulder preoperatively and 2 years after repair. Results. 100% of the patients
      were followed up. UCLA, ASES, and Constant questionnaires showed significant
      improvement compared with preoperatively (P < 0.001). Range of motion and SSI in
      flexion, abduction, and internal and external rotation also showed significant
      improvement (P < 0.001). MRI studies showed 24 cases of tear after repair (29%).
      Only 8 cases were a full-thickness tear. Conclusions. At two years of followup,
      in large and massive rotator cuff tears, an arthroscopic double row rotator cuff
      repair technique produces an excellent functional outcome and structural
      integrity.

PMID- 23533789
TI  - The use of an intra-articular depth guide in the measurement of partial thickness
      rotator cuff tears.
AB  - Purpose. The purpose of this study was to compare the accuracy of the
      conventional method for determining the percentage of partial thickness rotator
      cuff tears to a method using an intra-articular depth guide. The clinical utility
      of the intra-articular depth guide was also examined. Methods. Partial rotator
      cuff tears were created in cadaveric shoulders. Exposed footprint, total tendon
      thickness, and percentage of tendon thickness torn were determined using both
      techniques. The results from the conventional and intra-articular depth guide
      methods were correlated with the true anatomic measurements. Thirty-two patients
      were evaluated in the clinical study. Results. Estimates of total tendon
      thickness (r = 0.41, P = 0.31) or percentage of thickness tears (r = 0.67, P =
      0.07) using the conventional method did not correlate well with true tendon
      thickness. Using the intra-articular depth guide, estimates of exposed footprint
      (r = 0.92, P = 0.001), total tendon thickness (r = 0.96, P = 0.0001), and
      percentage of tendon thickness torn (r = 0.88, P = 0.004) correlated with true
      anatomic measurements. Seven of 32 patients had their treatment plan altered
      based on the measurements made by the intra-articular depth guide. Conclusions.
      The intra-articular depth guide appeared to better correlate with true anatomic
      measurements. It may be useful during the evaluation and development of treatment
      plans for partial thickness articular surface rotator cuff tears.

PMID- 23533790
TI  - Dental maturity in saudi children using the demirjian method: a comparative study
      and new prediction models.
AB  - A sample of 422 dental panoramic radiographs from individuals of known age (from
      4 to 14 yrs), sex (males: 217, females: 205), and ethnicity (Saudi) was
      collected. A dental maturation score for each individual was calculated using the
      Demirjian method. Age was then estimated using the original Demirjian curves and
      tables based on French-Canadian population and population-specific curves and
      tables for Arab (Saudi and Kuwaiti) and European (Belgian) populations. The
      differences between dental age and chronological age were analyzed and compared
      using paired t-tests, one-way ANOVA test, and a post hoc Scheffe's test. The
      Demirjian method utilizing French-Canadian standards presented significant
      difference between dental age and chronological age for the total sample and in
      the vast majority of age groups in both sexes. The mean overestimation of age was
      about 10 months (P < 0.05). The tables designed specifically for Arab populations
      had a significantly lower error than the tables designed for French-Canadian and
      Belgian populations. The latter had the largest error in age predication. New age
      prediction models and maturation scores for Saudi population were developed based
      on the Demirjian method using multinomial functions.

PMID- 23533791
TI  - Fecal calprotectin and clinical disease activity in pediatric ulcerative colitis.
AB  - Objective. To explore fecal calprotectin levels in pediatric ulcerative colitis
      (UC) in relation with the validated clinical activity index PUCAI. Methods. This
      study included all 37 children (median age 14 years) with UC who had calprotectin
      measured (PhiCal ELISA Test) by the time of PUCAI assessment at the Children's
      Hospital of Helsinki in a total of 62 visits. Calprotectin values <100  MU g/g of
      stool were considered as normal. The best cut-off value of each measure to
      predict 3-month clinical outcome was derived by maximizing sensitivity and
      specificity. Results. In clinically active disease (PUCAI >= 10), calprotectin
      was elevated in 29/32 patients (91% sensitivity). When in clinical remission, 26%
      (8/30) of the children had normal calprotectin but 7 (23%) had an exceedingly
      high level (>1000  MU g/g). The best cut-off value for calprotectin for
      predicting poor outcome was 800  MU g/g (sensitivity 73%, specificity 72%; area
      under the ROC curve being 0.71 (95%CI 0.57-0.85)) and for the PUCAI best cut-off
      values >10 (sensitivity 62%, specificity 64%; area under the ROC curve 0.714
      (95%CI 0.58-0.85)). Conclusion. The clinical relevance of somewhat elevated
      calprotectin during clinical remission in pediatric UC is not known and, until
      further evidence accumulates, does not indicate therapy escalation.

PMID- 23533792
TI  - Changes in plasma ghrelin and serum leptin levels after Cisplatin-based
      transcatheter arterial infusion chemotherapy for hepatocellular carcinoma.
AB  - Background and Objective. Cisplatin-based chemotherapy is widely recognized to
      cause severe gastrointestinal disorders like nausea, vomiting, and appetite loss.
      The aim of this study was to assess whether cisplatin-based transcatheter
      arterial infusion (TAI) chemotherapy reduces plasma ghrelin levels and food
      intake in hepatocellular carcinoma (HCC) patients. Methods. Seventeen patients
      with HCC who underwent cisplatin-based TAI chemotherapy (80-100 mg/body) were
      enrolled in this study. Changes in peptide hormones, including ghrelin and
      leptin, as well as cytokines, were measured before and after chemotherapy.
      Appetite was evaluated by visual analog scale (VAS) and food intake was scored by
      eleven stages (0-10). Results. Appetite and food intake were significantly
      decreased after chemotherapy (P < 0.05). Plasma acylated ghrelin levels before
      therapy and at day 1, day 7, and day 14 after chemotherapy were 10.4 +/- 7.2, 4.7
      +/- 4.7, 11.7 +/- 8.9, and 9.3 +/- 6.6 fmol/mL, respectively. The level on day 1
      was decreased significantly (P < 0.05). In contrast, the levels of leptin,
      granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1
      (MCP-1) on day 1 were increased significantly (P < 0.05). Conclusions. TAI for
      HCC reduced plasma acylated ghrelin levels, appetite, and food intake
      significantly. In addition, it increased serum leptin levels.

PMID- 23533793
TI  - Examination of the Anti-Inflammatory, Antioxidant, and Xenobiotic-Inducing
      Potential of Broccoli Extract and Various Essential Oils during a Mild DSS
      Induced Colitis in Rats.
AB  - Phytogenic compounds with antioxidant and anti-inflammatory properties are
      currently discussed as promising complementary agents in prevention and treatment
      of inflammatory bowel disease (IBD). Our study aimed to evaluate possible
      protective and curative effects of broccoli extract (BE) and of the essential
      oils of turmeric (Cuo), thyme (To), and rosemary (Ro) in a rat model with a mild
      dextran sulphate sodium- (DSS-) induced colitis. Therefore Wistar rats were fed a
      diet without an additive (Con) or diets with the addition of BE, Cuo, To, and Ro
      during the whole experiment. Pretreatment with Ro, Cuo, and To increased the
      expression of the tight junction protein Cldn3. All additives reduced mRNA of
      VCAM-1 which plays a crucial role in the first state of inflammatory response.
      Only Ro pretreatment affected the expression of the antioxidant enzymes HO1,
      GPx2, and of glutathione-S-transferases. All additives counteracted the DSS
      induced rise in COX2 and VCAM-1 expression. Colonic IL-10 was increased by Cuo,
      To, and Ro. During the recovery phase DSS pretreatment increased NF kappa B, VCAM
      1, and MCP-1: This response was counter-regulated by all additives. We conclude
      that the phytogenic additives tested have a promising anti-inflammatory potential
      in vivo and a particular role in the prevention of IBD.

PMID- 23533795
TI  - Depressed-Type Colonic Lesions and "De Novo" Cancer in Familial Adenomatous
      Polyposis: A Colonoscopist's Viewpoint.
AB  - Familial adenomatous polyposis (FAP) is the most common inherited polyposis
      syndrome. Almost all patients with FAP will develop colorectal cancer if their
      FAP is not identified and treated at an early stage. Although there are many
      reports about polypoid lesions and colorectal cancers in FAP patients, little
      information is available concerning depressed lesions in FAP patients. Several
      reports suggested that depressed-type lesions are characteristic of FAP and
      important in the light of their rapid growth and high malignancy. Here, we
      describe the occurrence of depressed-type lesions in FAP patients treated at our
      institution. Between April 2001 and March 2010, eight of 18 FAP patients had
      colorectal cancers. Depressed-type colorectal cancer was found in three patients.
      It should be kept in mind that depressed-type lesions occur even in FAP.

PMID- 23533794
TI  - Esophageal sarcoidosis: a review of cases and an update.
AB  - Sarcoidosis is a chronic disorder that can virtually affect any organ system in
      the body. Histologically, it is characterized by the presence of T lymphocytes,
      mononuclear phagocytes, and noncaseating granulomas. Most commonly affected are
      the intrathoracic structures, with 90% of the reported cases involving the lungs.
      Esophageal involvement in sarcoidosis is extremely rare. Dysphagia is the most
      common presentation in these patients and can be attributed to various mechanisms
      such as direct esophageal wall infiltration, extrinsic compression, cranial
      neuropathy, and brainstem involvement. A thorough online literature review
      revealed only 23 reported cases of esophageal involvement in sarcoidosis. This
      paper reviews these reported cases in detail along with newer diagnostic and
      treatment options, including direction of future therapy.

PMID- 23533796
TI  - Ritodrine Should Be Carefully Administered during Antenatal Glucocorticoid
      Therapy Even in Nondiabetic Pregnancies.
AB  - Aim. Antenatal glucocorticoid therapy (AGT) has been commonly used recently.
      However, this therapy has severe harmful effects such as maternal hyperglycemia.
      In Japan, ritodrine hydrochloride has been used as a tocolytic agent. In this
      study, we performed retrospective casecontrol study to clarify whether
      concomitant use of ritodrine and glucocorticoid was safe to pregnant women
      without diabetes mellitus. Methods. We reviewed the computerized records of
      pregnant women with pregestational diabetes (n = 9) and nondiabetes (n = 45) who
      gave birth at our hospital between 2002 and 2011. Cases and controls received
      AGT. Blood glucose after the therapy was analyzed, and additional volume of
      insulin was compared to that before the therapy. Results. From this study, 30
      units of insulin were necessary when performing AGT in diabetic pregnant women.
      And also, an increase in blood glucose of 40 mg/dL was seen after the therapy
      even in nondiabetic pregnant women. Blood glucose increased significantly in the
      group that also received ritodrine, and it was shown that the number of pregnant
      women who might develop ketoacidosis might increase 11-fold. Conclusions.
      Ritodrine should be carefully administered during antenatal glucocorticoid
      therapy. It may be necessary to adequately monitor blood glucose, when performing
      the therapy, even in nondiabetic pregnant women.

PMID- 23533797
TI  - Trends in ectopic pregnancies in eastern saudi arabia.
AB  - Background. The objective of this study was to estimate trends in ectopic
      pregnancies (EP) in a tertiary care center of Eastern Saudi Arabia. Method.
      Information about patients with ectopic pregnancies who had been admitted to King
      Fahd Hospital of the University, AlKhobar, between January 2000 and 31 December
      2011 was collected from a computerized hospital registry. Age-specific ectopic
      pregnancy incidence was calculated. The data was analyzed using SPSS (Statistical
      Package for the Social Sciences), version 14.0 (Chicago, IL, USA). Results. There
      were 274 EPs during the study period; the yearly incidence in terms of 24,098
      deliveries was 1.19%. The average age was 28.99 A 5.62 years. During a three-year
      period (2000-2002), the incidence was 0.92%; from 2003 to 2005, the incidence was
      1.01%; from 2006 to 2008, the incidence was 1.51%; and from 2009 to 2011, the
      incidence was 1.35%. Age-adjusted ectopic pregnancy incidence rates steadily
      increased from 92.23 per 10,000 women years during the period 2000-2002 to
      149.408 during the 2006-2008 period; since then, it has declined to 110.313 per
      10,000 women years. Conclusions. Our study reveals that the incidence of EP has
      decreased from what it had been during the mid-2000s but has remained
      significantly elevated when compared to the early 2000s.

PMID- 23533798
TI  - Effect of Infliximab on the UVB-Induced Apoptosis of Keratinocytes Infected by
      HPV38 E6/E7.
AB  - The question of the effect of anti-TNF-alpha in skin carcinogenesis is especially
      relevant in view of the increased use of these drugs for the treatment of
      autoinflammatory immune diseases. Since ultraviolet radiation and human
      papillomavirus are involved in skin carcinogenesis, we wished to investigate the
      effect of TNF-alpha antagonists on the UVB-induced apoptosis of keratinocytes
      infected by HPV38. Our results indicate that anti-TNF agent, infliximab, does not
      contribute to the survival of HPV38-transduced keratinocytes with UVB-induced DNA
      damages.

PMID- 23533799
TI  - A Comparison between Revised NCEP ATP III and IDF Definitions in Diagnosing
      Metabolic Syndrome in an Urban Sri Lankan Population: The Ragama Health Study.
AB  - Background. The prevalence of metabolic syndrome (MetS) within individual cohorts
      varies with the definition used. The aim of this study was to compare the
      prevalence of MetS between IDF and revised NCEP ATP III criteria in an urban Sri
      Lankan population and to investigate the characteristics of discrepant cases.
      Methods. 2985 individuals, aged 35-65 years, were recruited to the study.
      Anthropometric and blood pressure measurements and laboratory investigations were
      carried out following standard protocols. Results. Age and sex-adjusted
      prevalences of MetS were 46.1% and 38.9% by revised NCEP and IDF definitions,
      respectively. IDF criteria failed to identify 21% of men and 7% of women
      identified by the revised NCEP criteria. The discrepant group had more adverse
      metabolic profiles despite having a lower waist circumference than those
      diagnosed by both criteria. Conclusion. MetS is common in this urban Sri Lankan
      cohort regardless of the definition used. The revised NCEP definition was more
      appropriate in identifying the metabolically abnormal but nonobese individuals,
      especially among the males predisposed to type 2 diabetes or cardiovascular
      disease. Further research is needed to determine the suitability of the currently
      accepted Asian-specific cut-offs for waist circumference in Sri Lankan adults.

PMID- 23533800
TI  - Automatic Tube Compensation versus Pressure Support Ventilation and Extubation
      Outcome in Children: A Randomized Controlled Study.
AB  - Background. Automatic tube compensation (ATC) has been developed to overcome the
      imposed work of breathing due to artificial airways during spontaneous breathing
      trials (SBTs). Objectives. This study aimed to assess extubation outcome after an
      SBT (spontaneous breathing trial) with ATC compared with pressure support
      ventilation (PSV) and to determine the risk factors for extubation failure.
      Methods. Patients ready for extubation were randomly assigned to two-hour
      spontaneous breathing trial with either ATC or pressure support ventilation.
      Results. In the ATC group (n = 17), 11 (65%) patients passed the SBT with
      subsequent extubation failure (9%). While in PSV group (n = 19), 10 (53%)
      patients passed the SBT with subsequent extubation failure (10%). This
      represented a positive predictive value for ATC of 91% and PSV of 90% (P = 0.52).
      Five (83%) of the patients who failed the SBT in ATC group were reintubated. This
      represented a higher negative predictive value for ATC of 83% than for PSV which
      was 56%. None of the assessed risk factors were independently associated with
      extubation failure including failed trial. Conclusion. ATC was equivalent to PSV
      in predicting patients with successful extubation. A trial failure in ATC group
      is associated with but does not definitely predict extubation failure.

PMID- 23533801
TI  - Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema
      versus Oral Coffee Consumption in Healthy Male Subjects.
AB  - The objective of this study was to determine the pharmacokinetics of caffeine
      after single administration of a coffee enema versus coffee consumed orally in
      healthy male subjects. The study design was an open-label, randomized two-phase
      crossover study. Eleven healthy subjects were randomly assigned either to receive
      500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink
      coffee beverage. After a washout period of at least 10 days, all the subjects
      were switched to receive the alternate coffee procedure. Blood samples were
      collected immediately before and at specific time points until 12 hours after
      coffee administration in each phase. The mean caffeine content in both the coffee
      solution prepared for the coffee enema and the ready-to-drink coffee beverage was
      not statistically different. The C max and AUC of caffeine obtained from the
      coffee enema were about 3.5 times significantly less than those of the coffee
      consumed orally, despite having slightly but statistically faster T max. The t
      1/2 of caffeine obtained following both coffee procedures did not statistically
      differ. In summary, the relative bioavailability of caffeine obtained from the
      coffee enema was about 3.5 times significantly less than those of the coffee
      consumed orally.

PMID- 23533803
TI  - Clinical features of inflammatory myopathies and their association with
      malignancy: a systematic review in asian population.
AB  - Introduction. Idiopathic inflammatory myopathies (IIMs) are a group of chronic
      systemic autoimmune diseases that mainly affect the skeletal muscle. The common
      subtypes include adult dermatomyositis (DM), polymyositis (PM), and inclusion
      body myositis (IBM). Most of the earlier studies that described the clinical
      characteristics of IIM as well as their association with cancer were conducted in
      Western population. Our study is the first systematic review that summarizes the
      clinical data of DM/PM in Asian population. Methods. We identified 14 case series
      of DM/PM that met our eligibility criteria. We then compared this data with that
      from previous reports from Europe and North America. Results. Our systematic
      review included 2518 patients. Dermatomyositis is more common, with the ratio of
      dermatomyositis to polymyositis being 1.36 : 1. 69% of them were females with
      mean age of 45.5 years. Extramuscular manifestations, including
      arthritis/arthralgia, dysphagia, and interstitial lung disease, are found in one
      third of the patients. Malignancy was found in 10% of patients, with lung and
      nasopharyngeal carcinomas being the most common malignancies associated with
      these myopathies. Conclusion. Clinical presentation of PM/DM appears to be
      similar in both Western and Asian populations. However, the type of associated
      malignancies in Asians differs from that in Caucasians. Ethnic background should
      be one of the factors that clinicians should consider while screening for
      malignancy.

PMID- 23533804
TI  - A statewide case management, surveillance, and outcome evaluation system for
      children with special health care needs.
AB  - Objectives. To evaluate the feasibility of implementing a statewide children with
      special health care needs (CSHCN) program evaluation, case management, and
      surveillance system using a standardized instrument and protocol that
      operationalized the United States Health and Human Services CSHCN National
      Performance Measures. Methods. Public health nurses in local public health
      agencies in Washington State jointly developed and implemented the standardized
      system. The instrument was the Omaha System. Descriptive statistics were used for
      the analysis of standardized data. Results. From the sample of CSHCN visit
      reports (n = 127), 314 problems and 853 interventions were documented. The most
      common problem identified was growth and development followed by health care
      supervision, communication with community resources, caretaking/parenting,
      income, neglect, and abuse. The most common intervention category was
      surveillance (60%), followed by case management (24%) and teaching, guidance, and
      counseling (16%). On average, there were 2.7 interventions per problem and 6.7
      interventions per visit. Conclusions. This study demonstrates the feasibility of
      an approach for statewide CSHCN program evaluation, case management, and
      surveillance system. Knowledge, behavior, and status ratings suggest that there
      are critical unmet needs in the Washington State CSHCN population for six major
      problems.

PMID- 23533802
TI  - Scientific challenges and implementation barriers to translation of
      pharmacogenomics in clinical practice.
AB  - The mapping of the human genome and subsequent advancements in genetic technology
      had provided clinicians and scientists an understanding of the genetic basis of
      altered drug pharmacokinetics and pharmacodynamics, as well as some examples of
      applying genomic data in clinical practice. This has raised the public
      expectation that predicting patients' responses to drug therapy is now possible
      in every therapeutic area, and personalized drug therapy would come sooner than
      later. However, debate continues among most stakeholders involved in drug
      development and clinical decision-making on whether pharmacogenomic biomarkers
      should be used in patient assessment, as well as when and in whom to use the
      biomarker-based diagnostic tests. Currently, most would agree that achieving the
      goal of personalized therapy remains years, if not decades, away. Realistic
      application of genomic findings and technologies in clinical practice and drug
      development require addressing multiple logistics and challenges that go beyond
      discovery of gene variants and/or completion of prospective controlled clinical
      trials. The goal of personalized medicine can only be achieved when all
      stakeholders in the field work together, with willingness to accept occasional
      paradigm change in their current approach.

PMID- 23533805
TI  - Characteristics and outcomes of cocaine-related spontaneous intracerebral
      hemorrhages.
AB  - To date there is only one single-center study that has exclusively reported
      characteristics, location, and outcomes of spontaneous intracerebral hemorrhages
      (ICH) among cocaine users. We aimed to describe the radiological location and
      characteristics along with clinical outcomes of spontaneous ICH in a similar
      population. We conducted a retrospective chart review of consecutive patients
      admitted to a tertiary care hospital, with a spontaneous ICH, who had a urine
      drug screen performed within 48 hours of admission. Exposure to cocaine was
      defined by a positive urine drug screen within 48 hours of hospital admission.
      Demographics, radiographic features of ICH, and short-term clinical outcomes of
      patients with a positive urine drug screen were analyzed and compared with the
      cocaine negative group. Among the 102 patients analyzed, 20 (19.6%) had
      documented exposure to cocaine. There was a predominance of males in both groups
      with significantly more Blacks in the cocaine positive group (P = 0.0246). A
      statistically significant number of patients with cocaine use had ICH in a
      subcortical location (P = 0.0224) when compared to cocaine negative patients.
      There was no difference in GCS, ICH volume, intraventricular extension, ICU days,
      hospital days, hospital cost, mortality, and ICH score. ICH in cocaine use is
      more frequently seen in the subcortical location.

PMID- 23533806
TI  - Early and Late Shift of Brain Laterality in STG, HG, and Cerebellum with Normal
      Aging during a Short-Term Memory Task.
AB  - Evidence suggests that cognitive performance deteriorates in noisy backgrounds
      and the problems are more pronounced in older people due to brain deficits and
      changes. The present study used functional MRI (fMRI) to investigate the neural
      correlates of this phenomenon during short-term memory using a forward repeat
      task performed in quiet (STMQ) and in noise: 5-dB SNR (STMN) on four groups of
      participants of different ages. The performance of short-term memory tasks was
      measured behaviourally. No significant difference was found across age groups in
      STMQ. However, older adults (50-65 year olds) performed relatively poorly on the
      STMN. fMRI results on the laterality index indicate changes in hemispheric
      laterality in the superior temporal gyrus (STG), Heschl's gyrus (HG), and
      cerebellum, and a leftward asymmetry in younger participants which changes to a
      more rightward asymmetry in older participants. The results also indicate that
      the onset of the laterality shift varies from one brain region to another. STG
      and HG show a late shift while the cerebellum shows an earlier shift. The results
      also reveal that noise influences this shifting. Finally, the results support the
      hypothesis that functional networks that underlie STG, HG, and cerebellum undergo
      reorganization to compensate for the neural deficit/cognitive decline.

PMID- 23533808
TI  - Oxaliplatin and Bolus-Modulated 5-Fluorouracil as a Second-Line Treatment for
      Advanced Pancreatic Cancer: Can Bolus Regimens Replace FOLFOX When Considered for
      Second Line?
AB  - Objective. Comparing activity of 2 regimens combining oxaliplatin to bolus
      modulated fluorouracil as second line treatment in advanced pancreatic
      adenocarcinoma pretreated with gemcitabine-containing schedule. Methods. Forty
      eight patients with advanced pancreatic adenocarcinoma were randomly assigned to
      receive either FU 500 mg/m(2) IV bolus weekly *6 weeks plus leucovorin 500
      mg/m(2) IV weekly for 6 weeks during each 8-week cycle plus oxaliplatin 85
      mg/m(2) IV on weeks 1, 3, and 5 of each 8-week (FLOX) OR receive weekly
      intravenous infusions of oxaliplatin 40 mg/m(2), 5-FU 500 mg/m(2), and leucovorin
      250 mg/m(2) (3 weeks on, 1 week off). Results. Non progression(PR+SD) was found
      in 33.5% for first regimen and 29% for second regimen, and 37.5% had clinical
      benefit (FLOX regimen) compared to 50% in 3-weeks regimen. The median TTP was
      3.9,4 months respectively. Median OS was 8, 9 months for both regimens. Only one
      case in 3-weeks arm suffered from grade IV diarrhea. Two cases > grade 2
      neutropenia were observed; one in each treatment groups. Grade 3 anemia was
      recorded in 3 patients (2 in FLOX arm, one in 3-weeks arm). Conclusions. Both
      regimens showed encouraging efficacy, acceptable toxicity, and clinical benefit.

PMID- 23533809
TI  - ENETS TNM Staging Predicts Prognosis in Small Bowel Neuroendocrine Tumours.
AB  - Introduction. Small bowel neuroendocrine tumours (NETs) are the most common type
      of gastrointestinal neuroendocrine tumours. The incidence and prevalence of these
      tumours are on the rise. The aims of this study were to determine prognostic
      clinicopathological features and whether the ENETS TNM staging system predicts
      prognosis and also. Method. Clinical data was collected retrospectively from 138
      patients with histologically proven small bowel NETs managed at King's College
      Hospital. Histology was reviewed and small bowels tumours, were staged according
      to the ENETS TNM staging system. Results. Median age was 65 years (range 29-87).
      The 5-year survival was 79.5% and the 10-year survival was 48.5%. Resection of
      the primary tumour was associated with improved survival (120 versus 56 months, P
      < 0.05). On multivariate analysis prognostic factors were primary tumour
      resection and not having a carcinoid heart disease. TNM staging significantly
      separated survival of stage 2 and stage 3 from stage 4 NETs. Conclusion. Small
      bowel primary tumour resection and not having carcinoid heart disease are
      prognostic factors. The ENETS TNM staging and grading system appears to be of
      prognostic relevance to small bowel NETs.

PMID- 23533807
TI  - Pathways to breast cancer recurrence.
AB  - Breast cancer remains a deadly disease, even with all the recent technological
      advancements. Early intervention has made an impact, but an overwhelmingly large
      number of breast cancer patients still live under the fear of "recurrent"
      disease. Breast cancer recurrence is clinically a huge problem and one that is
      largely not well understood. Over the years, a number of factors have been
      studied with an overarching aim of being able to prognose recurrent disease. This
      paper attempts to provide an overview of our current knowledge of breast cancer
      recurrence and its associated challenges. Through a survey of the literature on
      cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various
      signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also
      examine the hypotheses that are currently under investigation for the prevention
      of breast cancer recurrence.

PMID- 23533811
TI  - Decreasing frequency of osteonecrosis of the jaw in cancer and myeloma patients
      treated with bisphosphonates: the experience of the oncology network of piedmont
      and aosta valley (north-Western Italy).
AB  - Background. Data concerning frequency of Osteonecrosis of Jaws (ONJ) are mostly
      based on single center experiences. Patients and Methods. Since 2005 a
      multidisciplinary study group collected data of cases of ONJ in patients treated
      with Bisphosphonates (BP) and observed in oncology and hematology centers of a
      regional network. Results. By December 2008, 221 cases were registered. We report
      details of 200 cases, identified after cross-checking reports from centres of
      medical oncology, haematology, and oral care. Primary neoplasm was breast cancer
      (39%), myeloma (32%), prostate cancer (16%), and other types of cancer (8%). In
      about 50% of the cases a history of dental extraction was present. Zoledronic
      acid was administered (alone or with other BP) to 178 patients (89%). Median time
      from first infusion to ONJ diagnosis was 21.0 (zoledronic acid only) and 39.0
      months (pamidronate only). The number of ONJ cases per year was 3 in 2003, 21 in
      2004, 58 in 2005, 60 in 2006, 37 in 2007, and 21 in 2008. Conclusion. The number
      of new ONJ cases in cancer and myeloma patients increased until 2006 and then
      reduced. The possible reasons of this trend (introduction of zoledronic acid;
      increase of ONJ awareness; diffusion of preventive dental measures; late
      modifications of BP prescription) are herein discussed.

PMID- 23533812
TI  - Tumor Inhibition by DepoVax-Based Cancer Vaccine Is Accompanied by Reduced
      Regulatory/Suppressor Cell Proliferation and Tumor Infiltration.
AB  - A successful cancer vaccine needs to overcome the effects of immune-suppressor
      cells such as Treg lymphocytes, suppressive cytokine-secreting Tr1 cells, and
      myeloid-derived suppressor cells (MDSCs), while enhancing tumor-specific immune
      responses. Given the relative poor efficacy associated with current cancer
      vaccines, a novel vaccine platform called DepoVax(TM) (DPX) was developed. C3
      tumor-challenged mice were immunized with HPV-E7 peptide in DPX- or conventional
      emulsion- (CE-) based vaccine. While control mice showed marked increase in
      Treg/MDSCs in spleen and blood, in mice treated with DPX-E7 the levels remained
      similar to tumor-free naive mice. Such differences were also seen within the
      tumor. Antigen-specific IL10-secreting CD4/CD8 T cells and TGF- beta (+)CD8(+) T
      cell frequencies were increased significantly in CE-treated and control mice in
      contrast to DPX-E7-immunized mice. Analysis of tumor-infiltrating cells revealed
      higher frequency of suppressor cells in untreated controls than in DPX-E7 group
      while the converse was true for tumor-infiltrating CD8 T cells. Immunization of
      tumor-bearing HLA-A2 transgenic mice with human vaccine DPX-0907, a peptide-based
      vaccine for breast/ovarian/prostate cancers, showed efficient induction of immune
      response to cancer peptides despite the presence of suppressor cells. Thus, this
      study provides the rationale for using DPX-based cancer vaccines in immune
      suppressed cancer patients, to induce effective anticancer immunity.

PMID- 23533813
TI  - Gene expression profile analysis of t1 and t2 breast cancer reveals different
      activation pathways.
AB  - Breast cancers today are of predominantly T1 (0.1 >= 2.0 cm) or T2 (>2 <= 5 cm)
      categories due to early diagnosis. Molecular profiling using microarrays has led
      to the notion of breast cancer as a heterogeneous disease both clinically and
      molecularly. Given the prognostic power and clinical use of tumor size, the
      purpose of this study was to search for molecular signatures characterizing
      clinical T1 and T2. In total 46 samples were included in the discovery dataset.
      After adjusting for hormone receptor status, lymph node status, grade, and tumor
      subclass 441 genes were differently expressed between T1 and T2 tumors. Focal
      adhesion and extracellular matrix receptor interaction were upregulated in the
      smaller tumors while p38MAPK signaling and immune-related pathways were more
      dominant in the larger tumors. The T-size signature was then tested on a
      validation set of 947 breast tumor samples. Using the T-size expression
      signatures instead of tumor size leads to a significant difference in risk for
      distant metastases (P < 0.001). If further confirmed, this molecular signature
      can be used to select patients with tumor category T1 who may need more
      aggressive treatment and patients with tumor category T2 who may have less
      benefit from it.

PMID- 23533814
TI  - Optimal planning target volume margins for elective pelvic lymphatic radiotherapy
      in high-risk prostate cancer patients.
AB  - Purpose. High-risk prostate cancer patients often receive radiotherapy (RT) to
      pelvic lymphatics (PLs). The aim of this study was to determine the safety margin
      around clinical target volume for PL (PL-CTV) to construct planning target volume
      for PL (PL-PTV) and for planning elective PL irradiation. Methods and Materials.
      Six patients who received RT to PL as part of prostate cancer treatment were
      identified. To determine average daily shifts of PL, the right and left IVs were
      contoured at 3 predetermined slices on the daily MV scans and their daily shifts
      were measured at these 3 levels using a measuring tool. Results. A total of 1,932
      observations were made. Daily shifts of IV were random in distribution, and the
      largest observed shift was 13.6 mm in lateral and 15.4 mm in AP directions. The
      mean lateral and AP shifts of IV were 2.1 mm (+/-2.2) and 3.5 mm (+/-2.7),
      respectively. The data suggest that AP and lateral margins of 8.9 mm and 6.5 mm
      are necessary. Conclusions. With daily alignment to the prostate, we recommend an
      additional PL-CTV to PL-PTV conversion margin of 9 mm (AP) and 7 mm (lateral) to
      account for daily displacement of PL relative to the prostate.

PMID- 23533810
TI  - Vitamin d: are we ready to supplement for breast cancer prevention and treatment?
AB  - Vitamin D deficiency is a potentially modifiable risk factor that may be targeted
      for breast cancer prevention and treatment. Preclinical studies support various
      antitumor effects of vitamin D in breast cancer. Numerous observational studies
      have reported an inverse association between vitamin D status, including
      circulating 25-hydroxyvitamin D (25(OH)D) levels, and breast cancer risk. The
      relationship between vitamin D and mammographic density, a strong predictor of
      breast cancer risk, remains unclear. Studies analyzing the link between genetic
      polymorphisms in vitamin D pathway genes and breast cancer incidence and
      prognosis have yielded inconsistent results. Vitamin D deficiency among breast
      cancer patients has been associated with poorer clinical outcomes and increased
      mortality. Despite a number of clinical trials of vitamin D supplementation, the
      efficacy, optimal dosage of vitamin D, and target blood level of 25(OH)D for
      breast cancer prevention have yet to be determined. Even with substantial
      literature on vitamin D and breast cancer, future studies need to focus on
      gaining a better understanding of the biologic effects of vitamin D in breast
      tissue. Despite compelling data from experimental and observational studies,
      there is still insufficient data from clinical trials to make recommendations for
      vitamin D supplementation for breast cancer prevention or treatment.

PMID- 23533815
TI  - Postoperative Complications following Nodal Dissection and Their Association with
      Melanoma Recurrence.
AB  - Background. Although postoperative complications are common after lymph node
      dissection, its association with disease recurrence has not yet been fully
      investigated. Methods. A retrospective review of a prospectively maintained
      database was conducted, looking at all malignant melanoma patients with sentinel
      nodes positive disease requiring axillary or inguinal dissection between 2002 and
      2011. Results. A total of 124 patients required nodal clearance from 317 patients
      with stage I/II malignant melanoma who had undergone sentinel lymph node biopsy.
      Of these, 104 patients met the inclusion criteria and were divided into inguinal
      lymph node dissections (ILND; n = 63) or axillary lymph node dissections (ALND; n
      = 41). Immunohistochemical deposits had higher detection rate in ALND (P = 0.01).
      The ILND patients had a higher recurrence rate (84.1% versus 63.4%; P = 0.02) and
      mortality (68.3% versus 48.8%; P = 0.05) without a significant difference in
      complications. In patients whom complications developed, 75% of the ILND group
      and 71.4% of the ALND group had disease recurrence, but without reaching a
      statistical value as an independent predictor of melanoma recurrence. Conclusion.
      Complications are common following ILND and ALND; however there is no significant
      difference in complications rates between the groups with some associations with
      recurrence without reaching a significant difference.

PMID- 23533816
TI  - Comparison of distal hypospadias repair in circumcised patients and uncircumcised
      patients.
AB  - Hypospadias is the most common anomaly in the male genital tract with an
      incidence of 0.8-8.2 per 1000 live male births. Routinely, hypospadias cases are
      repaired after one year of age, and it is recommended that a child with
      hypospadias not to be circumcised until hypospadias repair is completed. This
      study was conducted to determine whether or not circumcision prior to hypospadias
      repair increases the risk of complications. 30 circumcised patients and 30
      persons without a history of circumcision and hypospadias were enrolled in this
      study and underwent surgery for hypospadias repair. The results of surgery
      compared between two groups. In the uncircumcised group, the mean durations of
      surgery and hospitalization were 55.61 +/- 58.11 min and 3.17 +/- 1.79 days. In
      circumcised group, the mean duration of surgery and hospitalization were 66.17 +/
      33.65 minutes and 3.7 +/- 1.62 days. There was no significant difference between
      these criteria and other complications of the two groups. This study shows that
      postoperative complications in circumcised distal hypospadias patients do not
      increase. Cosmetic and functional results were excellent. If there are failures
      in therapy and in case of postoperative complications, it is better to notice
      other factors such as infection.

PMID- 23533817
TI  - Axon guidance mechanisms for establishment of callosal connections.
AB  - Numerous studies have investigated the formation of interhemispheric connections
      which are involved in high-ordered functions of the cerebral cortex in eutherian
      animals, including humans. The development of callosal axons, which transfer and
      integrate information between the right/left hemispheres and represent the most
      prominent commissural system, must be strictly regulated. From the beginning of
      their growth, until reaching their targets in the contralateral cortex, the
      callosal axons are guided mainly by two environmental cues: (1) the midline
      structures and (2) neighboring? axons. Recent studies have shown the importance
      of axona guidance by such cues and the underlying molecular mechanisms. In this
      paper, we review these guidance mechanisms during the development of the callosal
      neurons. Midline populations express and secrete guidance molecules, and
      "pioneer" axons as well as interactions between the medial and lateral axons are
      also involved in the axon pathfinding of the callosal neurons. Finally, we
      describe callosal dysgenesis in humans and mice, that results from a disruption
      of these navigational mechanisms.

PMID- 23533819
TI  - Gd(3+)-DTPA-Meglumine-Anionic Linear Globular Dendrimer G1: Novel Nanosized Low
      Toxic Tumor Molecular MR Imaging Agent.
AB  - Despite the great efforts in the areas of early diagnosis and treatment of
      cancer, this disease continues to grow and is still a global killer. Cancer
      treatment efficiency is relatively high in the early stages of the disease.
      Therefore, early diagnosis is a key factor in cancer treatment. Among the various
      diagnostic methods, molecular imaging is one of the fastest and safest ones.
      Because of its unique characteristics, magnetic resonance imaging has a special
      position in most researches. To increase the contrast of MR images, many
      pharmaceuticals have been known and used so far. Gadopentetate (with commercial
      name Magnevist) is the first magnetic resonance imaging contrast media that has
      been approved by the US Food and Drug Administration. In this study,
      gadopentetate was first synthesized and then attached to a tree-like polymer
      called dendrimer which is formed by polyethylene glycol core and surrounding
      citric acid groups. Stability studies of the drug were carried out to ensure
      proper synthesis. Then, the uptake of the drug into liver hepatocellular cell
      line and the drug cytotoxicity were evaluated. Finally, in vitro and in vivo MR
      imaging were performed with the new synthetic drug. Based on the findings of this
      research, connecting gadopentetate to dendrimer surface produces a stronger,
      safer, and more efficient contrast media. Gd(III)-diethylenetriamine pentaacetate
      meglumine-dendrimer drug has the ability to enter cells and does not produce
      significant cytotoxicity. It also increases the relaxivity of tissue and enhances
      the MR images contrast. The obtained results confirm the hypothesis that the
      binding of gadopentetate to citric acid dendrimer produces a new, biodegradable,
      stable, and strong version of the old contrast media.

PMID- 23533818
TI  - Influence of inflammation on poststroke plasticity.
AB  - Age-related brain injuries including stroke are a leading cause of morbidity and
      mental disability worldwide. Most patients who survive stroke experience some
      degree of recovery. The restoration of lost functions can be explained by
      neuronal plasticity, understood as brain ability to reorganize and remodel itself
      in response to changed environmental requirements. However, stroke triggers a
      cascade of events which may prevent the normal development of the plastic
      changes. One of them may be inflammatory response initiated immediately after
      stroke, which has been found to contribute to neuronal injury. Some recent
      evidence though has suggested that inflammatory reaction can be also
      neuroprotective. This paper attempts to discuss the influence of poststroke
      inflammatory response on brain plasticity and stroke outcome. We also describe
      the recent anti-inflammatory strategies that have been effective for recovery in
      experimental stroke.

PMID- 23533820
TI  - In Silico Prediction of Interactions between Site II on Human Serum Albumin and
      Profen Drugs.
AB  - Since binding of a drug molecule to human serum albumin (HSA) significantly
      affects the pharmacokinetics of the drug, it is highly desirable to predict the
      binding affinity of the drug. Profen drugs are a widely used class of
      nonsteroidal anti-inflammatory drugs and it has been reported that several
      members of the profen class specifically bind to one of the main binding sites
      named site II. The actual binding mode of only ibuprofen has been directly
      confirmed by X-ray crystallography. Therefore, it is of interest whether other
      profen drugs are site II binders. Docking simulations using multiple template
      structures of HSA from three crystal structures of complexes between drugs and
      HSA have demonstrated that most of the currently available profen drugs should be
      site II binders.

PMID- 23533821
TI  - Mandibular ameloblastoma in an elderly patient: a case report.
AB  - Ameloblastomas frequently occur in relatively young people, but are rarely seen
      in people aged 80 years or older. We report a case of mandibular ameloblastoma in
      an elderly patient with a review of the literature. The patient was a 82-year-old
      man who noticed swelling of the gingiva approximately 2 weeks prior to his
      initial visit. Computed tomography showed a radiolucent area with little
      radiopacity. Internal uniformity was observed at the site, with thinning of
      cortical bone which lacked continuity in some areas. The excision and curettage
      were performed under general anaesthesia. No recurrence has been observed 14
      months after surgery.

PMID- 23533822
TI  - Sanjad-sakati syndrome dental management: a case report.
AB  - Sanjad-Sakati syndrome (SSS) is a rare genetic disorder with autosomal recessive
      pattern of inheritance characterized by hypoparathyroidism, sever growth failure,
      mental retardation, susceptibility to chest infection, and dentofacial anomalies.
      A child with SSS was referred to the dental departmentseeking dental help for
      sever dental caries which was attributed to his dietary habits and quality of
      dental tissues. Full restorative rehabilitation was done under general
      anesthesia. Two years later, the child presented with recurrent caries affecting
      uncrowned teeth. High carries recurrence rate was blamed for the nutritional
      habits endorsed by the parents. Only steel crowned teeth survived such hostile
      oral environment which suggested shifting of treatment strategy towards full
      coverage restorations instead of classical cavity preparations and fillings
      during a second attempt for dental treatment under general anesthesia and for the
      dental treatment of two cousins of the same child. The author recommends
      effective health education for parents including the nature of their child's
      genetic disorder, nutritional needs, and dental health education to improve the
      life style of such children.

PMID- 23533823
TI  - Oromaxillary prosthetic rehabilitation of a maxillectomy patient using a magnet
      retained two-piece hollow bulb definitive obturator; a clinical report.
AB  - Resection of a malignant lesion involving the maxilla produces severe
      oromaxillary defect that can seriously jeopardize the normal phonetics of the
      patient. These defects are effectively managed by well-designed and fabricated
      obturator. This paper discusses the oromaxillary prosthetic rehabilitation of a
      maxillectomy patient using a magnet retained two-piece hollow bulb definitive
      obturator.

PMID- 23533824
TI  - Bilateral Mesiodens in Monozygotic Twins: 3D Diagnostic and Management.
AB  - Mesiodens is the most frequent type of supernumerary tooth and may occur in
      several forms, causing different local disorders, such as impaction of the
      anterior permanent teeth. High-resolution three-dimensional (3D) images have
      improved the diagnosis and treatment plan of patients with impacted and
      supernumerary teeth. The purpose of this paper was to report a case of two
      mesiodens in monozygotic twin boys with appropriate 3D diagnostic and treatment
      plan.

PMID- 23533825
TI  - Odontogenic fibromyxoma of maxilla: a rare case report.
AB  - Fibromyxoma is a rare odontogenic tumour which is benign, but locally aggressive.
      The etiology of these tumours is unknown, but because of its limitation to the
      teeth bearing areas and occasional presence of odontogenic epithelial fragments
      within the tumour which suggest that it is of odontogenic origin. It is a slow
      growing painless tumour that frequently occurs in second and third decades of
      life. Females are more commonly affected than males. The tumour can cause gradual
      expansion of the cortical plates and cause loosening and displacement of teeth,
      although root resorption may be rare. The surgical treatment of these tumours
      consists of complete enucleation or radical excision. The aim of this paper is to
      present the rarity of a fibromyxoma of the maxilla.

PMID- 23533826
TI  - Rare giant granular cell ameloblastoma: a case report and an immunohistochemical
      study.
AB  - Aims. The aim is to present a case of rare giant granular cell ameloblastoma and
      to review the pertinent literature highlighting the molecular aspects of its
      pathogenesis by analyzing the expression of CD-68, Bcl-2, and beta -catenin.
      Methods. H and E stained sections showed large odontogenic islands showing
      peripheral ameloblast-like cells and central stellate reticulum-like cells with
      extensive granular cell transformation surrounded by fibrous stroma. Polyclonal
      rabbit anti-CD 68, anti-Bcl2, and anti- beta -catenin were stained
      immunohistochemically. Results. CD-68 showed a moderate to strong staining
      intensity in granular cells. Moderate staining of Bcl-2 was expressed by the
      peripheral columnar cells of tumor islands and negative in the granular cells.
      Expression of beta -catenin was generally weak, except for only the focal areas
      that showed a moderate staining intensity and weak in peripheral cells.
      Conclusion. The present case of giant granular cell ameloblastoma is a rare
      entity. Development of monstrous size is indicative of ameloblastomas persistent
      growth. Granular cell transformation in ameloblastomas probably occurs as a
      consequence of extensive molecular changes. Immunohistochemical studies help us
      to know the pathogenesis of this granular cell ameloblastoma. Therefore, an
      effort has been made here to study the expression of Bcl-2, CD-68, and beta 
      catenin.

PMID- 23533827
TI  - Porous Titanium Granules and Blood for Bone Regeneration around Dental Implants:
      Report of Four Cases and Review of the Literature.
AB  - A regenerative procedure treating a local osseous defect around titanium dental
      implant using porous titanium granules is described in four patients. Porous
      titanium granules represent, for maxillofacial surgery, a new alternative in
      augmenting osseous defects. Its earliest application was in the field of
      orthopedics for stabilization of tibia plateau fractures and for reoperations in
      prosthetic fixation of femoral stems. There is emerging scientific evidence
      regarding titanium for its potential use in the maxillofacial area and porous
      titanium granules are now commercially available. The scientific background for
      the osteoconductive use of porous titanium granules is elucidated in this paper
      and the supporting literature is reviewed.

PMID- 23533828
TI  - Combined treatment with laser sintering and zirconium: a case report of
      dentinogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue
      that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis
      imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment
      protocol of these patients varies according to the clinical appearance. The case
      report here describes complete mouth rehabilitation of an 18-year-old male
      patient with OI and DI using direct metal laser sintering (DMLS) technique of
      metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive
      metal fabrication technology that is simpler, more precise, and healthier than
      conventional manufacturing and can be remarkably cost effective. Moreover, the
      technique affords highly accurate production of fixed partial dentures with ideal
      marginal fit and excellent mechanical properties. The patient was treated using a
      multidisciplinary strategy that focused on controlling caries, protecting teeth
      from further wear, obtaining an appropriate vertical dimension, and providing
      soft tissue support to return the facial profile to a normal appearance using new
      technology in the field of prosthetics.

PMID- 23533829
TI  - Amalgam tattoo mimicking mucosal melanoma: a diagnostic dilemma revisited.
AB  - Mucosal melanoma of the oral cavity is a rare but highly aggressive neoplasm.
      However, the clinicians need to be aware of the other and more frequent
      etiologies of intraoral pigmentation, such as amalgam tattoos. As amalgam has
      been extensively used for dental restorations and can cause pigmentations in the
      oral mucosa, this is a differential diagnosis not to be forgotten. We describe
      the characteristics of these two phenomena and present a case vignette
      illustrating the differential diagnostic issues. Other causes of intraoral
      pigmentation are summarized.

PMID- 23533830
TI  - Periodontal regeneration using platelet-derived growth factor in infrabony
      defects: a series of three cases.
AB  - The periodontal researchers and clinicians, in an effort to develop effective
      regenerative therapies, have sought to understand key events involved in the
      regeneration of periodontium. Polypeptide growth factors are a class of natural
      biological mediators which regulate key cellular events in tissue repair.
      Platelet-derived growth factor (PDGF) is the most thoroughly studied growth
      factor in periodontal regeneration. The present case series evaluate the
      effectiveness of platelet-derived growth factor (rh-PDGF-BB) in combination with
      beta-tricalcium phosphate ( beta -TCP) to achieve periodontal regeneration in 3
      infrabony defects.

PMID- 23533831
TI  - Inflammatory myofibroblastic tumor of the lung and the maxillary region: a benign
      lesion with aggressive behavior.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare mass-forming lesion
      characterized by fibroblastic or myofibroblastic spindle cell proliferation with
      varying degrees of inflammatory cell infiltration. Although it has been reported
      in virtually every organ in the body, the lung is the most common site of
      involvement. Extrapulmonary IMTs, although rare, have been reported and are
      characterized by different, more aggressive behavior. We report an extremely rare
      case of maxillary metastases of pulmonary IMT. Lung IMT was initially
      misdiagnosed, and oral lesion mimicked clinically and radiologically a radicular
      cyst. On histologic examination, cells exhibited diffuse and intense
      immunoreactivity for alpha -smooth muscle actin and vimentin whereas both
      pulmonary and oral IMTs presented absence of cellular atypia and lack of
      expressivity of oncogenic determinants. Distant metastases of lung IMT are
      extremely unusual, and this is the first report to our knowledge with this
      particular clinical course. Despite the possibility that the present case could
      also represent a metachronous multifocal IMT, with pulmonary and extrapulmonary
      lesions, similar histopathological and immunohistochemical patterns in lung and
      maxillary region suggest a metastatic course.

PMID- 23533832
TI  - Amelanotic melanoma masquerading as a granular cell lesion.
AB  - Amelanotic melanoma (AM) presents a diagnostic challenge due to its wide clinical
      presentations, lack of pigmentation, and varied histological appearances.
      Immunohistochemistry plays a crucial role in the diagnosis of these lesions.
      Amelanotic melanoma of oral mucosa is an uncommon lesion. We report a case of a
      50-year-old male patient with a growth on the anterior mandibular gingiva of
      seven-month duration. In the present case, histologically, the tumour resembled a
      granular cell lesion, which has not been reported previously in AM. Diagnosis was
      possible by a sequential panel of immunohistochemical markers, of which finally
      vimentin, S100, HMB45, and Melan-A were positive. The tumor was surgically
      excised, and postsurgical radiotherapy was given.

PMID- 23533833
TI  - Rehabilitation of posterior maxilla with zygomatic and dental implant after tumor
      resection: a case report.
AB  - Zygomatic implants have been used for dental rehabilitation in patients with
      insufficient bone in the posterior upper jaw, due to, for example, tumor
      resection, trauma, or atrophy. Zygomatic implants are an alternative to complex
      free or vascularized bone grafting and distraction osteogenesis. A 42-year-old
      male patient with a severe defect in the right posterior maxilla, starting from
      the first canine region, which had occurred after tumor resection 3 years
      earlier, was referred to our department. One zygomatic implant (Brenemark System,
      Nobel Biocare, Goteborg, Sweden) to the zygoma and one dental implant to the
      canine region were placed. After a 5-month osseointegration period, a fixed
      denture was fabricated and adapted to the implants. Although the surgical and
      prosthetic procedures for zygoma implants are not easy, the final outcomes can be
      successful with appropriate planning.

PMID- 23533834
TI  - Hereditary gingival fibromatosis: a review and a report of a rare case.
AB  - Hereditary gingival fibromatosis (HGF) is a rare condition which manifests itself
      by an enlarged gingival tissue covering teeth to various extents. The condition
      may occur isolated or as part of a syndrome. This paper presents a case of 9-year
      old female patient suffering from HGF with chief complaint of mouth protrusion.
      Cephalometric findings showed severe mandibular deficiency and vertical maxillary
      excess. Patient exhibited perioral muscle contraction on mouth closing. After
      discussing the treatment possibilities with the patient and her parents, the
      decision was made to wait until growth potential decreases (following the
      adolescent growth spurt) and to correct the problem with orthognathic surgery.

PMID- 23533835
TI  - Perforating disseminated necrobiosis lipoidica diabeticorum.
AB  - Perforating necrobiosis lipoidica is a very rare clinical variant which consists
      of degeneration and transepidermal elimination of the collagen with few cases
      reported in the literature. In two-thirds of the patients it associates with
      diabetes, with no relation with the glucose control. We present a 42-year-old
      female patient with a 7-year history of diabetes on insulin therapy, referred to
      our clinic with a 3-year history of multiple asymptomatic firm plaques
      disseminated on the upper and lower extremities. The clinical and histological
      findings proved the diagnosis of perforating necrobiosis lipoidica.

PMID- 23533836
TI  - A case of traumatic proptosis.
AB  - We present a case of traumatic proptosis in a competitive football player. This
      entity can occur with a significant decrease in vision, but in this case it did
      not. Some other causes of this condition are also discussed. A review of some
      traumatic conditions that may cause proptosis is provided as well.

PMID- 23533837
TI  - Adrenal insufficiency as a cause of acute liver failure: a case report.
AB  - Introduction. Many diseases and conditions can contribute to elevated liver
      enzymes. Common causes include viral and autoimmune hepatitis, fatty liver, and
      bile duct diseases, but, in uncommon cases like liver involvement in endocrine
      disorders, liver failure is also seen. Adrenal insufficiency is the rarest
      endocrine disorder complicating the liver. In the previously reported cases of
      adrenal insufficiency, mild liver enzymes elevation was seen but we report a case
      with severe elevated liver enzymes and liver failure due to adrenal
      insufficiency. Based on our knowledge, this is the first report in this field.
      Case Report. A 39-year-old woman was referred to emergency ward due to drowsiness
      and severe fatigue. Her laboratory tests revealed prothrombin time: 21 sec,
      alanine aminotransferase (ALT): 2339 IU/L, aspartate aminotransferase (AST): 2002
      IU/L, and ALP: 90 IU/L. No common cause of liver involvement was discovered, and
      eventually, with diagnosis of adrenal insufficiency and corticosteroid therapy,
      liver enzymes and function became normal. Finally, the patient was discharged
      with good general condition. Conclusion. With this report, we emphasize adrenal
      insufficiency (primary or secondary) as a reason of liver involvement in
      unexplainable cases and recommend that any increase in the liver enzymes, even
      liver failure, in these patients should be observed.

PMID- 23533838
TI  - Endogenous Cushing's Syndrome with Precocious Puberty in an 8-Year-Old Boy due to
      a Large Unilateral Adrenal Adenoma.
AB  - Adrenocortical tumors (ACTs) causing Cushing's syndrome are extremely rare in
      children and adolescents. Bilateral macronodular adrenocortical disease which is
      a component of the McCune-Albright syndrome is the most common cause of
      endogenous Cushing's syndrome. We report the case of a boy with Cushing's
      syndrome who presented with obesity and growth retardation. The child was
      hypertensive. The biochemical evaluation revealed that his serum cortisol levels
      were 25.80 MUg/dL, with a concomitant plasma ACTH level of 10.0 pg/mL and
      nonsuppressed serum cortisol on high-dose dexamethasone suppression test (HDDST)
      to be 20.38 MUg/dL. Computed tomography of the abdomen demonstrated a 8 * 6 * 5
      cm left adrenal mass with internal calcifications. Following preoperative
      stabilization, laparotomy was carried out which revealed a lobulated left adrenal
      mass with intact capsule weighing 120 grams. Histopathological examination
      revealed a benign cortical neoplastic lesion, suggestive of adrenal adenoma;
      composed of large polygonal cells with centrally placed nuclei and prominent
      nucleoli without capsular and vascular invasion. On the seventh postoperative
      day, cortisol levels were within normal range indicating biochemical remission of
      Cushing's syndrome. On followup after three months, the patient showed
      significant clinical improvement and had lost moderate amount of weight and
      adrenal imaging was found to be normal.

PMID- 23533839
TI  - Acromegaloid facial appearance: case report and literature review.
AB  - Pseudoacromegaly is characterized by an acromegalic appearance without any
      abnormality of growth hormone function. It may be caused by several congenital
      and acquired conditions. One such condition is the acromegaloid facial appearance
      (AFA) syndrome. This condition has been described in approximately eight
      cases/families. It encompasses a spectrum of acromegaloid physical findings,
      normal growth hormone (GH) and insulin-like growth factor one (IGF-1) levels, and
      variable mode of inheritance. The most common physical findings are coarse
      facies, bulbous nose, and thickened lips. We present a case and a review of the
      literature on this illness. The patient is a 57-year-old woman who was referred
      to the endocrinology division for evaluation of suspected acromegaly. She had an
      acromegaloid appearance since birth as well as a terminal hypertrichosis. Her
      endocrine laboratory evaluation and chromosomal analyses were normal. AFA needs
      to be considered when evaluating any patient with pseudoacromegaly. Additional
      cases/families need to be identified in order to better understand the clinical
      spectrum, clinical implications, and mode of inheritance of AFA.

PMID- 23533840
TI  - Extrahepatic textiloma long misdiagnosed as calcified echinococcal cyst.
AB  - Textiloma or gossypiboma is a retained surgical swab in the body after an
      operation and is a complication that can remain undetected for many years and may
      represent a diagnostic dilemma depending on its location. It may be confused with
      several focal lesions and an accurate history taking, combined with clinical and
      instrumental data, is key to suspecting the diagnosis. We report a case of
      abdominal textiloma that was initially misdiagnosed as echinococcal cyst and
      discuss the differential diagnosis based on sonographic features and the WHO-IWGE
      classification.

PMID- 23533841
TI  - Symptomatic primary (Al) amyloidosis of the stomach and duodenum.
AB  - Primary (AL) amyloidosis of the gastrointestinal tract is relatively rare, and
      symptomatic amyloidosis of the stomach is even more seldom. We present the case
      of a patient who was referred to upper endoscopy because of weight loss, nausea,
      and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies
      resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed
      amyloid depositions and further workup revealed that the patient also had cardiac
      and neuropathic involvements. The patient started treatment with dexamethasone,
      melphalan and bortezomib. After treatment was started the nausea and epigastric
      discomfort improved, and a reduction in the biochemical markers troponin T, NT
      proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper
      endoscopy in patients without a previously established diagnosis, but the unusual
      endoscopic findings and bleeding tendency after biopsy should be kept in mind by
      gastroenterologists.

PMID- 23533842
TI  - A rare cause of right upper quadrant pain in a 17-year-old female.
AB  - A 17-year-old Hispanic female presented to our hospital with complaints of right
      upper quadrant abdominal pain, vomiting, and fever. Physical exam was positive
      for hepatomegaly. Abdominal computed tomography showed multiple hypoechoic liver
      masses. Liver biopsy was done, which was diagnostic for hepatic epithelioid
      hemangioendothelioma.

PMID- 23533843
TI  - Video capsule retention in inflammatory bowel disease: an unusual presentation
      and discussion of retrieval methods.
AB  - Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the
      gastrointestinal (GI) tract. Video capsule endoscopy (VCE) is widely used to
      investigate the small bowel, and capsule retention is the most serious potential
      complication. Endoscopic and surgical management has been reported, but in the
      absence of bowel obstruction, there is little consensus as to which should be
      employed. In this case report, we describe a patient who was investigated with
      VCE for weight loss and anaemia. He had previously undergone colectomy with
      ileoanal pouch formation for ulcerative colitis (UC). Capsule retention occurred
      at an ileal stricture and he was subsequently diagnosed with Crohn's disease
      (CD). We describe his medical management and successful capsule retrieval using
      endoscopic methods. This case also highlights the importance of screening for
      intestinal strictures in an atypical presentation of UC following colectomy.

PMID- 23533844
TI  - Diagnosis of bardet-biedl syndrome in consecutive pregnancies affected with
      echogenic kidneys and polydactyly in a consanguineous couple.
AB  - Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathic human genetic
      disorder with variable expression that is difficult to diagnose in pregnancy
      without known risk factors. Homozygosity testing has been shown to be a useful
      tool in identifying BBS mutations and candidate genes in affected individuals. We
      present the first case of prenatal diagnosis of BBS in consecutive pregnancies
      aided by homozygosity testing via SNP microarray analysis. This case demonstrates
      a novel approach to the evaluation of recurrent echogenic kidneys in
      consanguineous couple with no significant family history.

PMID- 23533845
TI  - A New Case of dic(1;15)(p11;p11) in AML M1: Apropos of a Case and a Review of the
      Literature.
AB  - Acute myelogenous leukemia (AML) develops as the consequence of a series of
      genetic changes in a hematopoietic precursor cell. Specific cytogenetic
      abnormalities have been identified by karyotype analysis in AML. One of the rare
      chromosomal abnormalities is a dicentric chromosome, which is defined as an
      aberrant chromosome having two centromeres. In the literature, a limited number
      of cases have been reported with dic(1;15) in myeloid disorders, but only one
      case has been reported with in acute megakaryoblastic leukemia. Herein, we report
      a case of acute myelogenous leukemia without maturation with a
      dic(1;15)(p11;p11), resulting in trisomy of the long arm of chromosome 1. To
      date, this is the second case of dic(1;15) in acute myelogenous leukemia and the
      first case in acute myeloblastic leukemia without maturation.

PMID- 23533846
TI  - A case of hemophagocytic lymphohistiocytosis in a patient with chronic
      lymphocytic leukemia after treatment with fludarabine, cyclophosphamide, and
      rituximab chemotherapy, with autopsy findings.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is rarely described in association with
      chronic lymphocytic leukemia (CLL), mostly triggered by disease progression or
      concurrent infection. A 68-year-old male received 4 cycles of fludarabine,
      cyclophosphamide, and rituximab (FCR) for CLL and achieved a complete response.
      Twenty-four days after the last chemotherapy, he presented with febrile
      neutropaenia and was diagnosed with HLH. The diagnosis was based upon persistent
      fever, pancytopenia, hyperferritinemia, splenomegaly, and hemophagocytosis on
      bone marrow aspirate. He began treatment with dexamethasone, cyclosporine, and
      etoposide. Fever resolved and hyperferritinemia improved but pancytopenia
      persisted. He died 13 days later from septic shock with positive blood cultures.
      A limited postmortem examination was performed and biopsies were taken from bone
      marrow, liver, and spleen. Biopsies demonstrated abundant hemophagocytosis by the
      activated macrophage as stained by CD68. There was no evidence of residual CLL as
      demonstrated by the lack of lymphocytes which was confirmed by the negative
      staining of CD79a. Chemotherapy appears to be responsible for the development of
      HLH in this patient. This is the second reported case of HLH developing after a
      rituximab-containing chemotherapy.

PMID- 23533847
TI  - A case of abdominal sarcoidosis in a patient with acute myeloid leukemia.
AB  - The allogeneic bone marrow transplantation usually preceded by induction
      chemotherapy, in fit patients, represents the gold standard in the acute myeloid
      leukaemia. In the last years, many trials have been set up with the view of
      improving the number of remissions during the induction by adding new drugs.
      Several early or late side effects have been described in the literature. We
      herein present a patient with acute myeloid leukaemia patient who, after
      chemotherapy, developed ascites that turned out to be abdominal sarcoidosis.

PMID- 23533848
TI  - High-output cardiac failure revealing primary plasma cell leukemia.
AB  - High-output cardiac failure in multiple myeloma (MM) is related to arteriovenous
      shunting in bone infiltrate disease. We describe such a complication in a patient
      with primary plasma cell leukemia (pPCL) without bone disease. We review the
      mechanisms that could be involved. As previously described, traditional cardiac
      failure therapy is not effective. pPCL therapy should not be delayed.

PMID- 23533849
TI  - Postpartum acquired hemophilia: a rare cause of postpartum hemorrhage.
AB  - A 36-year-old female started having postpartum vaginal bleeding after normal
      vaginal delivery. She underwent hysterectomy for persistent bleeding and was
      referred to our institution. An elevation of PTT and normal PT made us suspect
      postpartum acquired hemophilia (PAH), and it was confirmed by low factor VIII
      activity levels and an elevated factor VIII inhibitor. Hemostasis was achieved
      with recombinant factor VII concentrates and desmopressin, and factor eradication
      was achieved with cytoxan, methylprednisolone, and plasmapheresis.

PMID- 23533850
TI  - Bendamustine associated with irreversible ascending paralysis.
AB  - Bendamustine is an alkylating agent currently used in the treatment of
      lymphoproliferative disorders. Many adverse effects, including a rare case of
      reversible neurotoxicity, have been reported in association with bendamustine.
      Herein, we report the first case of irreversible ascending paralysis related to
      bendamustine.

PMID- 23533851
TI  - West nile virus infection in pregnancy.
AB  - A recent outbreak of West Nile virus has allowed for observations as to the
      clinical course of this emerging pathogen during pregnancy. We present three
      cases of West Nile virus infection during pregnancy. Case 1 presented at term
      with focal subjective weakness and fever. With supportive care, her symptoms were
      resolved within 7 days, and she subsequently delivered an unaffected term infant.
      Case 2 presented in the first trimester with fever and headache. Her symptoms
      were resolved in 8 days with supportive care. Case 3 was diagnosed during the
      first trimester during workup of nonspecific respiratory symptoms, with
      resolution of all symptoms in 24 days. Obstetricians need to be aware of the
      varied clinical presentation of West Nile virus during pregnancy.

PMID- 23533852
TI  - Disseminated Aspergillosis due to Aspergillus niger in Immunocompetent Patient: A
      Case Report.
AB  - Invasive aspergillosis is a major cause of morbidity and mortality in
      immunocompromised patients. Many cases of pulmonary, cutaneous, cerebral, and
      paranasal sinus aspergillosis in immunocompetent patient were defined in
      literature but disseminated aspergillosis is very rare. Here we present an
      immunocompetent case with extrapulmonary disseminated aspergillosis due to
      Aspergillus niger, totally recovered after effective antifungal treatment with
      voriconazole.

PMID- 23533853
TI  - A case of mixed infections in a patient presenting with acute febrile illness in
      the tropics.
AB  - Concurrent infections with more than one etiological agent can result in an
      illness with overlapping symptoms, resulting in a situation where the diagnosis
      and management of such a patient could be challenging. We report a case of vivax
      malaria in a patient who was also serologically positive for leptospirosis and
      dengue.

PMID- 23533854
TI  - Role of carbamazepine in the symptomatic treatment of subacute sclerosing
      panencephalitis: a case report and review of the literature.
AB  - We describe the clinical presentation and clinical course of subacute sclerosing
      panencephalitis in a 13-year-old previously healthy boy who recently immigrated
      to the United States from Iraq. He presented with macular retinopathy, followed
      by progressive myoclonus and encephalopathy. After extensive workup, a diagnosis
      of subacute sclerosing panencephalitis was suspected by the presence of period
      epileptiform discharges on electroencephalogram and confirmed by elevated measles
      titers in the cerebrospinal fluid. Combination immunomodulatory therapy with
      isoprinosine, ribavirin, and intra-Ommaya interferon alpha did not result in
      clinical improvement. Within days following the administration of carbamazepine,
      there was remarkable improvement in the myoclonus and he was able to ambulate
      independently for a period of 4 months at which time he unfortunately progressed
      to a vegetative state. This case highlights the importance of carbamazepine as a
      potential first line symptomatic treatment of subacute sclerosing panencephalitis
      and provides a review of the literature on the subject.

PMID- 23533855
TI  - Postcoital internal carotid artery dissection presenting as isolated painful
      horner syndrome: a case report.
AB  - Postcoital artery dissection is a rare condition. Here we report a 40-year-old
      male patient with painful Horner syndrome related to postcoital internal carotid
      artery (ICA) dissection. In neurologic examination of the patient, semiptosis,
      enophthalmus, and myosis were observed on the left side. There were no carotid
      bruits. On T1-weighted and fat-suppressed cranial MRI, hyperintensity consistent
      with intramural hematoma was observed within cervical and temporal petrous
      segments of left ICA. On cervical and cranial MRA, marked decrease in the
      calibration of C1 and C2 segments of the left ICA was remarkable. The patient was
      diagnosed as left ICA dissection and anticoagulant therapy was initiated. A
      prominent improvement was noted in clinical findings during two months of
      followup period.

PMID- 23533856
TI  - Isolated brainstem involvement in a patient with hypertensive encephalopathy.
AB  - Hypertensive encephalopathy typically presents with headache, confusion, and
      bilateral parietooccipital vasogenic edema. Brainstem edema in hypertensive
      encephalopathy usually occurs in association with typical supratentorial parieto
      occipital changes and is usually asymptomatic. We report here a patient with
      hypertensive encephalopathy, with isolated brain stem involvement on magnetic
      resonance imaging (MRI). Rapid treatment of hypertension resulted in clinical and
      radiological improvement. Prompt recognition of the condition and aggressive
      treatment of hypertension in such patients is crucial to relieve edema and
      prevent life-threatening progression.

PMID- 23533857
TI  - Anaplastic medullary ependymoma presenting as subarachnoid hemorrhage.
AB  - A-41-year old man presented with violent thunderclap headache and a bilateral
      proprioceptive sensibility deficit of the upper limbs. Cerebral CT scan and MRI
      were negative. Lumbar puncture confirmed subarachnoid hemorrhage (SAH), but
      cerebral angiography was negative. Three months later, the patient presented with
      paraparesis, and a thorough work-up revealed a diffuse, anaplastic extramedullary
      C7-D10 ependymoma with meningeal carcinomatosis considered the source of
      hemorrhage. The patient went through a D5-D8 laminectomy, temozolomide
      chemotherapy, and radiotherapy. The situation remained stable for a few months.
      In this paper, we would like to emphasize that spinal masses should be considered
      in cases of SAH with negative diagnostic findings for aneurysms or arteriovenous
      malformation.

PMID- 23533858
TI  - Coexistence of Neurofibromatosis Type-1 and MTHFR C677T Gene Mutation in a Young
      Stroke Patient: A Case Report.
AB  - In neurofibromatosis type-1 (NF1), cerebrovascular disorders are rarely
      encountered although vasculopathy is a well-known complication. Several mutations
      seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of
      hyperhomocysteinemia and homocystinuria, a considerable risk factor for
      cardiovascular and cerebrovascular disorders, by leading to enzymatic
      inactivation. In the paper, a 31-year-old young stroke female patient with the
      coexistence of neurofibromatosis and MTHFR C677T gene mutation was presented.

PMID- 23533859
TI  - Ovarectomy despite Negative Imaging in Anti-NMDA Receptor Encephalitis: Effective
      Even Late.
AB  - Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune antibody-mediated
      neuropsychiatric disorder. The disorder is known to be associated with ovarian
      teratoma and predominantly affects young women. Here, we report the case of a 34
      year-old woman with anti-NMDAR encephalitis, in which detailed investigations
      gave no specific hint for an ovarian teratoma. Despite this, and due to a
      continuous severe clinical syndrome, an ovarectomy was performed and histological
      examination revealed an occult teratoma. The ovarectomy led to a remarkable
      improvement even with a long term intensive care treatment for 11 months. The
      most important lesson to be learned from this instructive case is that even
      though none of the investigations was indicative for an ovarian teratoma,
      including an explorative laparoscopy with biopsy, there still may be an occult
      ovarian teratoma. This shows that tumour search and diagnosis are extremely
      important in patients presenting with anti-NMDAR encephalitis, and a laparotomy
      and ovarectomy is justified. Furthermore, removal of the teratoma even 11 months
      after a very severe course is still therapeutically effective.

PMID- 23533860
TI  - Primary congenital lymphedema complicated by hydrops fetalis: a case report and
      review of the literature.
AB  - Introduction. Primary congenital lymphedema is a rare disorder associated with
      insufficient development of lymphatic vessels. Usually most patients present with
      lower extremity edema seen sonographically. Rarely primary congenital lymphedema
      may be associated with severe lymphatic dysfunction resulting in hydrops fetalis.
      Case. A 27-year-old primigravida with a family history of leg swelling throughout
      multiple generations was diagnosed early in the third trimester with hydrops
      fetalis. Delivery was undertaken at 32 weeks for nonreassuring fetal status and
      the infant expired at approximately 45 minutes of life. Primary congenital
      lymphedema was confirmed via molecular testing of the vascular endothelial growth
      factor receptor-3 gene. Discussion. The diagnosis of PCL is suspected prenatally
      when ultrasound findings coincide with a positive family history of chronic lower
      limb lymphedema. Isolated PCL is rarely associated with significant
      complications. Rarely, however, widespread lymphatic dysplasia may occur,
      possibly resulting in nonimmune hydrops fetalis.

PMID- 23533861
TI  - Complete androgen insensitivity syndrome: a rare case of disorder of sex
      development.
AB  - Androgen Insensitivity Syndrome (AIS) could be considered as a disease that
      causes resistance to androgens actions, influencing both the morphogenesis and
      differentiation of the body structures, and systems in which this hormone exerts
      its effects. It depends on an X-linked mutations in the Androgen Receptor (AR)
      gene that express a variety of phenotypes ranging from male infertility to
      completely normal female external genitalia. The clinical phenotypes of AIS could
      vary and be classified into three categories, as complete (CAIS), partial (PAIS),
      and mild (MAIS) forms, according to the severity of androgen resistance. We will
      describe a case of CAIS in a 16-year-old patient.

PMID- 23533862
TI  - Appendiceal endometriosis and carcinoid presented as acute appendicitis in
      pregnancy: a rare case report and review of the literature.
AB  - A 22-year-old pregnant woman presented at the twenty-seventh week of gestation in
      the Emergency Department with acute abdominal pain and right iliac fossa
      tenderness. Urgent MRI was done and was suggestive of acute appendicitis. A
      laparoscopy was performed that confirmed an inflamed and purulent appendix that
      was removed. The technique used is described in detail. The histopathologic
      findings were those of acute appendicitis, carcinoid, and endometriosis of the
      appendix. We report the first case of this extremely rare triad presented in
      pregnancy.

PMID- 23533863
TI  - Uterine carcinosarcoma in a patient with didelphys uterus.
AB  - Background. Didelphys uterus is a noncommon finding in women. Till now, few cases
      with benign mesenchymal tumors in patients with didelphys uterus are described.
      We present a case of a patient with carcinosarcoma arising in a didelphys uterus.
      Case. A 73-year-old patient presented with profuse watery postmenopausal
      bleeding. On examination under anesthesia, left and right cervixes were
      identified. Tumor extended from the left cervix into the lower third of the
      vagina and was adherent to the right vaginal sidewall. There was no evidence of
      parametrial extension. Tissue was sent for biopsy which revealed high-grade
      uterine carcinosarcoma. Two uterine fundi and two vaginas in keeping with uterine
      didelphys were identified on imaging. The patient underwent vaginal excision of
      the protruding tumor measuring 8 * 6 cm with harmonic scalpel followed by total
      abdominal hysterectomy and bilateral salpingooophorectomy. Although a number of
      pelvic and paraaortic lymph nodes were also identified on imaging, she was not
      planned for lymphadenectomy after MDT (multidisciplinary team) discussion because
      of her comorbidities. The final histology confirmed the diagnosis. Conclusion.
      According to our knowledge, this is the second case of carcinosarcoma arising in
      didelphys uterus in the world literature.

PMID- 23533864
TI  - Supraclavicular lymphadenopathy: initial manifestation of metastasis in carcinoma
      of cervix.
AB  - Introduction. Carcinoma of cervix rarely metastasizes to cervical lymph nodes and
      is associated with poor prognosis. To date, only few case reports have been
      reported in the medical literature. Here, we report a case of this unusual
      manifestation of carcinoma of cervix. Case Presentation. A 39-year-old Saudi
      woman who was treated three years ago for bulky IB stage carcinoma of cervix with
      total abdominal hysterectomy and bilateral salpingo-oophorectomy and adjuvant
      chemoradiation presented to us during her routine follow-up visit with left
      supraclavicular lymphadenopathy. Staging workup revealed additional para-aortic
      nodal and osseous metastases. The biopsy of left supraclavicular mass confirmed
      the diagnosis of carcinoma of the cervix. Patient was started on chemotherapy and
      bisphosphonates. Conclusion. Supraclavicular lymph nodes are a rare site of
      metastasis in carcinoma of cervix, and this can be explained by outlining the
      drainage of the lymphatic system from the cervix. Supraclavicular lymphadenopathy
      is associated with variable prognosis.

PMID- 23533865
TI  - Cesarean section and right femur fracture: a rare but possible complication for
      breech presentation.
AB  - Background. The breech extraction of the fetus through the vagina has a greater
      risk of hip fracture compared with the extraction by abdominal route. Case. A
      2390 g female infant was delivered at 39 weeks by elective cesarean section for
      breech presentation. The newborn sustained a fracture of the right femur. A
      simple immobilization of the limb in extension led to a complete healing of the
      fracture without sequelae. Conclusion. Caesarean delivery reduces the risk of
      causing a traumatic injury of the newborn compared to vaginal delivery,
      especially with breech presentation but does not eliminate this possible
      accidental complication.

PMID- 23533866
TI  - Massive Hematometra due to Congenital Cervicovaginal Agenesis in an Adolescent
      Girl Treated by Hysterectomy: A Case Report.
AB  - A case of massive hematometra with a bicornuate uterus in a 14-year-old mentally
      handicapped girl complicated by vaginal agenesis and absent cervix is presented.
      She was managed by abdominal hysterectomy and right salpingo-oophorectomy that
      included the ovarian cystadenoma. The left ovary was conserved. This treatment
      was considered appropriate for this patient.

PMID- 23533867
TI  - Obstetrical Management of an Extremely Overweight Pregnant Woman (184 kg bw) with
      Special Attention on Thromboprophylaxis.
AB  - The 27-year-old pregnant woman has been overweight since her childhood.
      Endocrinological assessments did not confirm hormonal disease. Her pregnancy was
      without complication. A signs of intrauterine distress were observed and elective
      caesarean section was performed under heparin protection because of anatomy
      unsuitable for delivery per vias naturals. The mother's bodyweight was 184 kg. By
      monitoring the change in fX activity LMWH treatment (Enoxaparin) initiated with a
      dose of 120 mg twice daily and then the dose was gradually elevated to 200 mg
      twice daily thereby achieving the lower range of the desired therapeutic effect.
      Apart from mild disorder of wound healing, the recovery was free of complication.
      The patient suffered from thrombophilia (extremely overweight, pregnant,
      thrombophlebitis under the knee, surgery, and postoperative immobilization). In
      case of quite extreme bodyweight there is no dosage recommendation or clinical
      practice for LMWH. Because of the extreme overweight and the therapeutic dose
      titration test of heparin, monitoring of fX activity by measurement of
      inhibition, dosage of heparin other than the recommended (abdominal wall instead
      of upper arm SC), and the very fluctuating heparin dosage which is well
      correlating with clinical practice, it is reasonably expected that this case will
      take interest.

PMID- 23533868
TI  - Postpartum pneumomediastinum and subcutaneous emphysema: two case reports.
AB  - Spontaneous pneumomediastinum associated with subcutaneous emphysema is a rare
      condition also known as Hamman's syndrome. It can also be seen postpartum. We
      present two cases of subcutaneous emphysema associated with childbirth in
      nulliparous women, both of which resolved spontaneously.

PMID- 23533869
TI  - Vaginal Atrophy following Long-Term Depot Medroxyprogesterone Acetate Use: A Case
      Report.
AB  - Depot medroxyprogesterone acetate (DMPA) is a commonly used form of
      contraception, with noncontraceptive benefits for the user. The mode of action is
      through the suppression of ovulation. It leads to hypoestrogenism which causes
      dryness of the vagina and dyspareunia. We present in this paper a patient that
      was very symptomatic with regard to vaginal atrophic changes determined by
      vaginal cytology. This side effect may become increasingly more common as we see
      more long-term use of DMPA.

PMID- 23533870
TI  - Hepatic epithelioid hemangioendothelioma and the danger of misdiagnosis: report
      of a case.
AB  - Malignant hepatic epithelioid hemangioendothelioma (HEHE) is a rare malignant
      tumor of vascular origin. Nonspecific symptoms and the absence of experience of
      surgeons, radiologists, and histopathologists due to the rarity of HEHE make the
      diagnosis of this entity very challenging. Misdiagnosis is not a rare event, and
      the consequences of such an event are catastrophic. We report a case of a patient
      suffering from HEHE in which the initial diagnosis was hepatocellular carcinoma
      (HCC). The presence of normal laboratory values, liver function tests, tumor
      markers along with the absence of a chronic liver disease, or any other
      predisposing factors for HCC, was in contrast with the diagnosis of HCC. Clinical
      suspicion drove us to the repetition of a liver biopsy and the reevaluation of
      the sample by a more experience histopathology department in liver tumors. The
      last biopsy confirmed the diagnosis of HEHE, and the patient escaped any
      unnecessary treatment for a nonexisting HCC.

PMID- 23533871
TI  - Posterior Reversible Encephalopathy Syndrome Associated with FOLFOX Chemotherapy.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity
      characterized by headaches, altered mental status, seizures, visual loss, and
      characteristic imaging pattern in brain MRI. The cause of PRES is not yet
      understood. We report a case of a 27-year-old woman that developed PRES after the
      use of FOLFOX 5 (oxaliplatin/5-Fluoracil/Leucovorin) chemotherapy for a
      colorectal cancer.

PMID- 23533872
TI  - Synchronous BALT Lymphoma and Squamous Cell Carcinoma of the Lung: Coincidence or
      Linkage?
AB  - A 72-year-old man presented with weight loss, fever, and malaise. Chest
      radiograph and CT revealed two large ill-defined masses in middle and left lower
      lobes. CT-guided biopsy of left lower lobe mass disclosed bronchus-associated
      lymphoid tissue (BALT) lymphoma. Middle lobe mass was considered second deposit
      in contralateral lung. The patient received chemotherapy for BALT. Followup CT
      disclosed regression of left lower lobe mass and stability of middle-lobe mass
      and of right paratracheal lymph nodes. CT-guided biopsy of middle-lobe mass
      revealed squamous cell lung carcinoma. Surgical biopsy of right paratracheal
      lymph nodes revealed malignancy. Disease was staged T3, N2, and M0. Combined
      chemotherapy for lung cancer and BALT lymphoma was initiated.

PMID- 23533873
TI  - A case of multiple myeloma coexisting with primary hyperparathyroidism and review
      of the literature.
AB  - Hypercalcemia is a common medical problem with an estimated prevalence of 15%
      among hospitalized patients. Multiple myeloma (MM) and primary
      hyperparathyroidism (PHPT) are among the most common causes of hypercalcemia but
      coexistence of both pathologic processes in a patient is an extremely rare
      phenomenon. In this paper we have discussed a patient presenting with this rare
      phenomenon. We have also provided a comprehensive review of the scientific
      literature published on codiagnosis of MM and PHPT.

PMID- 23533874
TI  - Aggressive multimodal approach for anaplastic thyroid cancer and long-term
      survival.
AB  - Anaplastic thyroid cancer (ATC) comprises 1-2% of all thyroid cancers and is one
      of the most aggressive cancers with a median survival rate of around four months.
      The average 5-year survival rate has been reported to be around 3.6%. In this
      paper, we have discussed management and prognostic variables of a patient with
      ATC who has survived for more than 5 years. A 59-year-old female was referred to
      our facility for an elective thyroid and parathyroidectomy for concerns of
      thyroid papillary cancer and hyperparathyroidism. At the time of surgery, the
      tumor mass had invaded the muscular layer of esophagus; radicle thyroidectomy
      parathyroidectomy along with removal of muscle layer of esophagus was performed,
      and diagnosis of ATC was made. The patient was treated with chemoradiation with a
      good treatment response and no recurrence of tumor for two and a half years until
      PET/CT followed by wedge biopsy of lung confirmed ATC recurrence. The patient was
      treated with another course of radiation treatment with a good treatment
      response. Since then, the patient has been following in our outpatient oncology
      clinic and has no evidence of tumor recurrence. Aggressive multimodal approach of
      combining radicle surgery with chemoradiation treatment in select patients of ATC
      with no distant metastasis helps improve prognosis.

PMID- 23533875
TI  - PET/CT Imaging in Oncology: Exceptions That Prove the Rule.
AB  - (18)F-FDG PET/CT is a diagnostic three-dimensional non-invasive device, routinely
      employed in neurology, cardiology, and oncology, and which contributes to patient
      care giving functional informations about glucose metabolism. In particular,
      staging, restaging, follow-up and response to treatment of tumors are the most
      common applications in oncologic field. Many neoplasms show increased glucose
      metabolism and consequent (18)F-FDG uptake. Nevertheless, some relative
      differentiated cancers, such as clear cell carcinoma of the kidney and
      bronchioloalveolar adenocarcinoma, show tipically faintly/no uptake resulting in
      a consequent negative PET/CT scan. This case report represents an extreme case in
      which three relative well-differentiated cancer forms, all characterized by low
      glucose metabolism, affect the same patient at the same time while (18)F-FDG
      PET/CT scan is negative.

PMID- 23533876
TI  - Arteriovenous malformation in temporal lobe presenting as contralateral ocular
      symptoms mimicking carotid-cavernous fistula.
AB  - Aim. To report a rare case of arteriovenous malformation in temporal lobe
      presenting as contralateral orbital symptoms mimicking carotid-cavernous fistula.
      Method. Interventional case report. Results. A 31-year-old Malay gentleman
      presented with 2-month history of painful progressive exophthalmos of his left
      eye associated with recurrent headache, diplopia, and reduced vision. Ocular
      examination revealed congestive nonpulsating 7 mm exophthalmos of the left eye
      with no restriction of movements in all direction. There was diplopia in left
      lateral gaze. Left IOP was elevated at 29 mmHg. Left eye retinal vessels were
      slightly dilated and tortuous. CT scan was performed and showed right temporal
      arteriovenous malformation with a nidus of 3.8 cm * 2.5 cm with right middle
      cerebral artery as feeding artery. There was dilated left superior ophthalmic
      vein of 0.9 mm in diameter with enlarged left cavernous sinus. MRA and carotid
      angiogram confirmed right temporal arteriovenous malformation with no carotid
      cavernous fistula. Most of the intracranial drainage was via left cavernous
      sinus. His signs and symptoms dramatically improved following successful
      embolisation, completely resolved after one year. Conclusion. Intracranial
      arteriovenous malformation is rarely presented with primary ocular presentation.
      Early intervention would salvage the eyes and prevent patients from more disaster
      morbidity or fatality commonly due to intracranial haemorrhage.

PMID- 23533877
TI  - Prosthetic rehabilitation of a patient with an ocular defect: a simplified
      approach.
AB  - Mutilation of a portion of a face can cause a heavy impact on the self-image and
      personality of an individual. Acceptable cosmetic results usually can be obtained
      with a facial prosthesis. This paper describes prosthetic rehabilitation of a 60
      year-old male patient having a left ocular defect. A technique to fabricate heat
      polymerizing polymethyl methacrylate was illustrated. The resultant prosthesis
      was structurally durable and aesthetically acceptable with satisfactory
      retention. The importance of meticulous treatment planning to tackle the
      challenges faced in fabricating an ocular prosthesis is explained with the
      relevant literature.

PMID- 23533878
TI  - Erratum to "Surgical Management of Pseudophakic Malignant Glaucoma via Anterior
      Segment-Peripheral Iridectomy Capsulo-Hyaloidectomy and Anterior Vitrectomy".

PMID- 23533879
TI  - The Massive Bleeding after the Operation of Hip Joint Surgery with the Acquired
      Haemorrhagic Coagulation Factor XIII(13) Deficiency: Two Case Reports.
AB  - Two women, aged 81 and 61, became haemorrhagic after surgery. Their previous
      surgeries were uneventful with no unexpected bleeding observed. Blood tests prior
      to the current surgeries indicated normal values including those related to
      coagulation. There were no problems with the current surgeries prior to leaving
      the operating room. At 3 hours after the surgery, the 81-year-old patient had an
      outflow of the drain at 1290 grams and her blood pressure decreased. She had
      disseminated intravascular coagulation (DIC). The 61-year-old woman had repeated
      haemorrhages after her current surgery for a long time. Their abnormal
      haemorrhages were caused by a deficiency of coagulation factor XIII(13). The
      mechanism of haemorrhagic coagulation factor XIII(13) deficiency is not
      understood, and it is a rare disorder. The only diagnostic method to detect this
      disorder is to measure factor XIII(13) activity in the blood. In this paper, we
      used Arabic and Roman numerals at the same time to avoid confusion of coagulation
      factor XIII(13) with coagulation factor VIII(8) that causes hemophilia A.

PMID- 23533880
TI  - Intra-articular dislocation of the patella.
AB  - We present an unusual case of a chronic, irreducible intra-articular dislocation
      of the patella in an elderly nursing home resident. The patient had been unable
      to weight bear for 3 weeks. Radiographs in the emergency department (ED)
      confirmed the intra-articular dislocation with the superior pole lodged in the
      intercondylar notch. She underwent two failed closed reduction attempts and
      subsequently required an open reduction under general anaesthesia.

PMID- 23533881
TI  - Delayed Neurologic Deficit due to Foraminal Stenosis following Osteoporotic Late
      Collapse of a Lumbar Spine Vertebral Body.
AB  - We report an 85-year-old woman with an L3 vertebral body fracture who presented
      with back pain, bilateral leg pain, and weakness after four months of
      conservative treatment. Because of unstable pseudoarthrosis, the L3 vertebral
      body collapsed in the standing position and the L3 nerve root was compressed. The
      indicated surgery decompressed the L3-L4 foramen and fused the unstable segment.
      The back pain and neurologic symptoms improved significantly following surgery.
      We propose that delayed neurologic deficit following an osteoporotic fracture of
      the lumbar body may be caused not only by retropulsion of vertebral body
      fragments with significant canal compromise, but also by foraminal stenosis with
      the late collapse of the vertebral fracture. This new pathomechanism for delayed
      neurologic deficit has not been previously described. If a collapse takes place
      in the caudal part of the vertebral body below the base of the pedicle, spine
      surgeons should be aware of the possibility of foraminal stenosis.

PMID- 23533882
TI  - "White cord syndrome" of acute tetraplegia after anterior cervical decompression
      and fusion for chronic spinal cord compression: a case report.
AB  - Paralysis is the most feared postoperative complication of ACDF and occurs most
      often due to an epidural hematoma. In the absence of a clear etiology, inadequate
      decompression or vascular insult such as ischemia/reperfusion injury are the
      usual suspects. Herewith we report a case of complete loss of somatosensory
      evoked potentials (SSEPs) during elective ACDF at C4-5 and C5-6 followed by
      postoperative C6 incomplete tetraplegia without any discernible technical cause.
      A postoperative MRI demonstrated a large area of high signal changes on T2
      weighted MRI intrinsic to the cord "white cord syndrome" but no residual
      compression. This was considered consistent with spinal cord gliosis with
      possible acute edema. The acute decompression of the herniated disc resulted in
      cord expansion and rush-in reperfusion. We postulate that this may have led to
      disruption in the blood brain barrier (BBB) and triggered a cascade of
      reperfusion injuries resulting in acute neurologic dysfunction. At 16 months
      postoperatively our patient is recovering slowly and is now a Nurick Grade 4.

PMID- 23533883
TI  - Pulmonary embolism after arthroscopic rotator cuff repair: a case report.
AB  - Total hip/knee arthroplasty may cause venous thromboembolism (VTE) as a
      postoperative complication. However, there are few reports on VTE after
      arthroscopic shoulder surgery. We report a patient who developed pulmonary
      embolism (PE) 6 days after arthroscopic rotator cuff repair but recovered without
      sequelae. In this case, the possibility of DVT of the lower limbs was denied by
      contrast-enhanced CT. Most possibly, the source of PE was deep vein thrombosis
      (DVT) of the upper limb under Desault fixation which showed arthroscopic surgery
      related swelling postoperatively.

PMID- 23533884
TI  - Dynamic Change of VOR and Otolith Function in Intratympanic Gentamicin Treatment
      for Meniere's Disease: Case Report and Review of the Literature.
AB  - Intratympanic gentamicin treatment (IGT) is an evidence-based therapeutic option
      for recurrent vertigo attacks in Meniere's disease (MD). Today, in MD it is
      possible to monitor changes of vestibular receptor function, induced by IGT, with
      objective test methods such as the video head impulse test (vHIT) and cervical
      and ocular vestibular evoked myogenic potentials (cVEMP, oVEMP) in a dynamic,
      time-and frequency-dependent manner. We report on a 65-year-old female patient
      with recurrent vertigo attacks in a right-sided MD, where receptor function was
      followed up before and up to 4 weeks after IGT (time dynamic). Quantitative
      changes of vestibular function (frequency dynamic) were detected with bithermal
      calorics and vHIT, with air-conducted sound (ACS) cVEMP and bone-conducted
      vibration (BCV) oVEMP at 500 Hz. The horizontal vestibuloocular reflex (hVOR)
      gain in vHIT decreased successively until the 4th week with the appearance of
      catch-up covert and catch-up overt refixation saccades, and side asymmetry
      increased in caloric testing. Saccular function was extinguished within 4 weeks,
      whereas utricular function was diminished after 4 weeks. Monitoring vestibular
      receptor function with objective test methods provides a quantitative insight
      into the dynamic activity of vestibular function and is therefore applicable in
      order to adjust IGT regimen at different therapeutic stages.

PMID- 23533885
TI  - Tonsillitis caused by vomiting in a patient with bulimia nervosa: a case report
      and literature review.
AB  - A 32-year-old lady presented to our ENT service with worsening tonsillitis. This
      was one of multiple attacks; all of which had all followed periods of self
      induced vomiting due to the patient suffering with bulimia nervosa. Here we
      present the first ever case report of such a case of tonsillitis and a review of
      the literature of otolaryngology manifestations and complications of bulimia
      nervosa.

PMID- 23533886
TI  - A rare localization of actinomycosis mimicking ulcerative malignancy.
AB  - Actinomycosis is a chronic, suppurative, and granulomatous process caused by
      Actinomycetes, saprophytic bacteria normally residing in the oral cavity. It can
      involve any organ, but the cervicofacial disease is the most frequent.
      Pharyngolayngeal involvement is rare and usually occurs secondary to the oral or
      cervical disease. There are few cases of primary pharyngolaringeal actinomycosis
      described in the literature. A rare case of pharyngeal actinomycosis mimicking an
      ulcerative malignancy in a 63-year-old man is reported. The patient was treated
      successfully with long-term antibiotic therapy. The clinical and pathological
      features and the aspects of diagnosis and treatment of cervicofacial
      actinomycosis are discussed.

PMID- 23533887
TI  - Schwannoma with an uncommon upper lip location and literature review.
AB  - Schwannomas are usually single, encapsulated, and benign tumors of the nerve
      sheath that arise from the perineural Schwann cells. Schwannomas are mostly seen
      in the fourth decade. Despite its location in the head and neck region is 25-45%,
      lip location of schwannoma are very rare. We present a case of a upper lip
      schwannoma in the pediatric age and review the literature.

PMID- 23533888
TI  - Recombinant human thyrotropin-aided radioiodine therapy in tracheal obstruction
      by an invading well-differentiated thyroid carcinoma.
AB  - Papillary thyroid carcinomas (PTCs) usually extend to lymph nodes in the neck and
      mediastinum. Rarely, they invade the neighboring upper airway anatomical
      structures. We report a 56-year-old woman who presented with symptoms of upper
      airway obstruction. Imaging studies revealed a lesion derived from the thyroid
      which invaded and obstructed the trachea, which appeared to be a highly
      differentiated PTC. Total thyroidectomy was performed, with removal of the
      endotracheal part of the mass along with the corresponding anterior tracheal
      rings. Two months later, a whole body I(131) scan after recombinant human thyroid
      stimulating hormone (rh-TSH) administration was performed and revealed a residual
      mass in upper left thyroid lobe. Subsequently, 150 mCi I(131) were given
      following rh-TSH administration. Nine months later, there was no sign of residual
      tumor. This case is the first one reported in the literature regarding rh-TSH
      administration prior to RAI ablation in a PTC obstructing the trachea.

PMID- 23533889
TI  - Pitfalls in neuroimaging of headache: a case report and review of the literature.
AB  - Headache is a common symptom, with a lifetime prevalence of over 90% of the
      general population in the United Kingdom (UK). It accounts for 4.4% of
      consultations in primary care and 30% of neurology outpatient consultations.
      Neuroimaging is indicated in patients with red flag features for secondary
      headaches. The guidelines recommend CT or MRI scan to identify any intracranial
      pathology. We present a unique case where the initial noncontrast CT scan failed
      to identify a potential treatable cause for headache. A middle aged man presented
      with headache and underwent a CT scan without contrast enhancement. The scan was
      reported as normal. The headache persisted for years and the patient underwent a
      staging CT scan to investigate an oropharyngeal cancer. This repeat CT scan
      utilized contrast enhancement and revealed a meningioma. Along with other
      symptoms, headache is an established presenting complaint in patients with
      meningioma. The contrast enhanced CT brain proved superior to a nonenhanced CT
      scan in identifying the meningioma. In a patient with persistent headache where
      other causes are excluded and a scan is to be requested, perhaps contrast
      enhanced CT is a better option than a plain CT scan of brain.

PMID- 23533890
TI  - Pulmonary mucus gland adenomas: are they always of endobronchial localization?
AB  - Mucus gland adenoma is an extremely rare benign lung tumor, presumed to arise
      from the bronchial mucus glands; it is a TTF-1 negative tumor, centrally located,
      causing the clinical manifestations of obstruction. We report a TTF-1 negative
      mucus gland adenoma, arising into the medial bronchopulmonary segment, lacking
      any relation to a bronchus.

PMID- 23533891
TI  - Giant accessory right-sided suprarenal spleen in thalassaemia.
AB  - An accessory spleen is defined as ectopic splenic tissue that develops due to
      failure of fusion of cells during embryonic development as they migrate from the
      midline to the left upper quadrant. While benign, complications may arise which
      include trauma, torsion, or infarction of the ectopic tissue. Additionally,
      patients who have had a splenectomy secondary to treatment for previous pathology
      such as a haematological malignancy or idiopathic thrombocytopenia purpura may
      experience persistent symptoms due to the accessory splenic tissue. The presence
      of an accessory spleen is therefore of significant diagnostic and therapeutic
      importance. To the best of the authors' knowledge, this case is the second and
      largest reported case of a giant right suprarenal accessory spleen and highlights
      the difficulty in differentiation of these masses from malignant adrenal tumours.

PMID- 23533892
TI  - Malignant mullerian mixed tumor of the uterine cervix with a small cell
      neuroendocrine carcinoma component.
AB  - Malignant Mullerian mixed tumors (MMMTs) of the uterine cervix are extremely
      rare, accounting for 0.005% of all cervical malignancies. To date, only
      approximately 50 well-documented cases have been reported. Although several
      epithelial components have been described in cervical MMMTs, small cell
      neuroendocrine carcinoma (SCC) has not appeared in the English literature. We
      present a 43-year-old woman, para 2 gravida 2, who had MMMT with SCC and
      rhabdomyosarcoma components in the uterine cervix. She was referred to our
      hospital because of a cervical mass with an abnormal Pap smear result. Cervical
      biopsy revealed SCC. After neoadjuvant chemotherapy with balloon-occluded
      arterial infusion, she underwent type II radical hysterectomy with pelvic
      lymphadenectomy. Histological analysis revealed that the cervical tumor comprised
      SCC and rhabdomyosarcoma components. Genotype analysis indicated human
      papillomavirus type 18. She underwent concurrent chemoradiation therapy. The
      patient had been free of the disease and showed no evidence of recurrence 38
      months after operation.

PMID- 23533893
TI  - Metastatic melanoma presenting as intussusception in an 80-year-old man: a case
      report.
AB  - Malignant melanoma of the gastrointestinal tract is an uncommon neoplasm that
      could be primary or metastatic. Small intestine represents the most common site
      for the metastatic melanoma; however, it could be found anywhere in the
      gastrointestinal tract. Intussusception is a rare cause of intestinal obstruction
      in adults compared to children. In 90% of the cases, the underlying cause can be
      found, and in 65% of the cases, intussusception is caused by the neoplastic
      process. The majority of the neoplasms are benign, and about 15% are malignant.
      Metastatic melanoma is one of the most common metastatic malignancies to the
      gastrointestinal tract; however, the premortem diagnosis is rarely made. Here, we
      report an uncommon clinical presentation of metastatic melanoma causing
      intussusception in an 80-year-old man. This diagnosis should be considered in a
      differential diagnosis in any patient who presents with gastrointestinal symptoms
      and a history of melanoma.

PMID- 23533894
TI  - Precursor B-Cell Acute Lymphoblastic Leukemia/Lymphoma with L3 Morphology,
      Philadelphia Chromosome, MYC Gene Translocation, and Coexpression of TdT and
      Surface Light Chains: A Case Report.
AB  - Acute lymphoblastic leukemia is predominantly found in children. It is a neoplasm
      of precursor cells or lymphoblasts committed to either a B- or T-cell lineage.
      The immature cells in B-acute lymphoblastic leukemia/lymphoma can be small or
      medium sized with scant or moderate cytoplasm and typically express B-cell
      markers such as CD19, cytoplasmic CD79a, and TdT without surface light chains.
      These markers, along with cytogenetic studies, are vital to the diagnosis,
      classification, and treatment of these neoplasms. We present an unusual case of a
      precursor B-cell ALL, in an 82-year-old woman, who presented with pancytopenia
      and widespread lymphadenopathy. The cells show L3 morphology (Burkitt-like
      lymphoma) with coexpression of TdT and surface light chains in addition to an MYC
      gene translocation and Philadelphia chromosome.

PMID- 23533896
TI  - Erratum to "A Rare Presentation of Concurrent Scedosporium apiospermum and
      Madurella grisea Eumycetoma in an Immunocompetent Host".

PMID- 23533895
TI  - Primary thyroid-like follicular renal cell carcinoma: an emerging entity.
AB  - Primary thyroid-like follicular carcinoma of the kidney is a rare but newly
      emerging histological variant of renal cell carcinoma RCC, with only nine cases
      reported in the literature to date. We present a further case of this unique
      condition, discuss the workup and typical histological findings, and review the
      literature regarding this rare histological variant.

PMID- 23533897
TI  - Retroperitoneal cystic lymphangioma: a diagnostic and surgical challenge.
AB  - A lymphangioma is a benign proliferation of lymph vessels, producing fluid-filled
      cysts that result from a blockage of the lymphatic system. The incidence of
      abdominal lymphangiomas is unknown; however they account for from 3% to 9.2% of
      all pediatric lymphangiomas, with retroperitoneal lymphangioma representing less
      than 1% of abdominal lymphangiomas. Due to rarity, preoperative diagnosis is
      often difficult.

PMID- 23533898
TI  - Neurofibromatosis type 1 complicated by atypical coarctation of the thoracic
      aorta.
AB  - Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant genetic
      disorder with a prevalence of 1 in 3,000 (0.03%) at birth. Clinical features are
      cafe-au-lait macules, intertriginous freckling, dermal neurofibroma, iris
      hamartoma (Lisch nodules), and learning disability. NF1 vasculopathy is a serious
      but underrecognized complication involving the cerebrovascular and cardiovascular
      systems. The incidence of hypertension in patients with NF1 is around 1% and is
      associated mainly with renal artery stenosis in children. Only a few cases of
      thoracic aortic coarctation in association with hypertension and
      neurofibromatosis have been reported. Here we describe the case of a 4-year-old
      girl who presented with NF1 and hypertension due to atypical coarctation of the
      thoracic aorta. The diagnosis of coarctation of the thoracic aorta at the Th5-to
      Th6 level was made following catheterization with a pressure gradient of 40 mmHg.
      The patient underwent surgery comprising resection of the coarctation of the
      thoracic aorta and graft interposition. On the basis of our findings, annual
      assessment of blood pressure is advised for patients with NF1.

PMID- 23533899
TI  - Left sided oesophageal lung: a diagnostic challenge.
AB  - Bronchopulmonary foregut malformations (BPFMs) include a wide variety of
      malformations such as intralobar or extralobar pulmonary sequestration, foregut
      duplication cysts, and diverticula of the gastrointestinal or pulmonary tree
      (Srikanth et al., 1992). Those anomalies in which a tract between the respiratory
      and alimentary systems exists are termed communicating bronchopulmonary foregut
      malformations (CBPFMs). Most infants with CBPFMs suffer from respiratory
      distress, and an accurate diagnosis may be difficult to make at the patient's
      initial presentation. Herein we report such a case which posed a diagnostic
      challenge to us. This baby however survived and is doing well on a 2-year
      followup.

PMID- 23533900
TI  - Linezolid is associated with serotonin syndrome in a patient receiving
      amitriptyline, and fentanyl: a case report and review of the literature.
AB  - We report a unique case of an adverse interaction between the oxazolidinone
      antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid
      analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral
      arterial disease and sepsis, under empirical antibiotic treatment. We also
      summarize the current relevant literature as identified via PubMed, EMBASE, and
      PsycINFO as well as reference sections of selected articles.

PMID- 23533901
TI  - Pulmonary embolism related to amisulpride treatment: a case report.
AB  - Venous thromboembolism has been associated with antipsychotic drugs, but the
      underlying mechanisms are largely unknown. Hypotheses that have been made include
      body weight gain, sedation, enhanced platelet aggregation, increased levels of
      antiphospholipid antibodies, hyperhomocysteinemia, whereas hyperprolactinemia has
      recently attracted attention as a potential contributing factor. The highest risk
      has been demonstrated for clozapine, olanzapine, and low-potency first-generation
      antipsychotics; however, presently there is no data for amisulpride. In the
      present paper we describe a case of pulmonary embolism in a female bipolar
      patient, receiving treatment with amisulpride, aripiprazole, and paroxetine.
      Although a contribution of aripiprazole and paroxetine cannot completely be ruled
      out, the most probable factor underlying the thromboembolic event seems to be
      hyperprolactinemia, which was caused by amisulpride treatment. Increased plasma
      levels of prolactin should probably be taken into account during the monitoring
      of antipsychotic treatment as well as in future research concerning venous
      thromboembolism in psychiatric settings.

PMID- 23533902
TI  - Empyema in a woman with cystic fibrosis: a cautionary tale.
AB  - Cystic fibrosis (CF) is a disease which predisposes individuals to recurrent
      infective exacerbations of suppurative lung disease; however, empyema is a rare
      complication in these patients. Empyemas secondary to Staphylococcus aureus and
      Burkholderia cepacia have been described in patients with CF. We report the case
      of pleural empyema with mixed S. aureus and Pseudomonas aeruginosa infection in a
      34-year-old woman with CF, which was managed with ultrasound-guided pigtail
      catheter insertion, fibrinolysis, and antibiotic therapy. Physicians should be
      aware of this unusual complication in CF patients, especially those receiving an
      immunosuppressive therapy.

PMID- 23533903
TI  - A Rare Cause of Diffuse Parenchymal Lung Disease together with Granulomatous
      Reaction: Pulmonary Amyloidosis.
AB  - Amyloidosis is a heterogeneous group of disorder associated with the deposition
      of protein in an abnormal fibrillar form. Primary Sjogren's syndrome (PSS) is a
      systemic inflammatory disorder that commonly affects the exocrine glands. The
      reported frequency of pulmonary involvement in PSS varies widely, ranging from 9%
      to 75%. Pulmonary involvement occurs in light-chain (AL) amyloidosis and is
      uncommon in the reactive (AA) and hereditary forms. Herein we present a case of
      PSS associated diffuse multinodular amyloidosis in the lung. We followed up the
      patient without treatment for three years. There are only minimal lung symptoms
      related to lung infiltration. In conclusion, pulmonary involvement in SS is an
      extremely rare clinical manifestation and usually has a good survival rate
      without treatment.

PMID- 23533904
TI  - Cerebral phaeohyphomycosis in a patient with neurosarcoidosis on chronic steroid
      therapy secondary to recreational marijuana usage.
AB  - Cerebral phaeohyphomycosis is often a fatal disease that typically takes a
      hematogenous spread after inhalation or accidental skin inoculation of pathogens.
      We present a patient with a history of heavy marijuana smoking while being on
      chronic steroid therapy for treatment of neurosarcoidosis who was found to have
      multiple brain abscesses from Curvularia sp. This is a ubiquitous soil-dwelling
      dematiaceous fungus that is generally thought to affect solely plants, but there
      is increasing evidence in the literature of it affecting humans and animals. We
      review the radiographic findings of neurosarcoidosis and cerebral
      phaeohyphomycosis as well as the pathophysiology of dematiaceous fungi
      infections.

PMID- 23533905
TI  - Mixed capillary venous retroperitoneal hemangioma.
AB  - We report a case of mixed capillary venous hemangioma of the retroperitoneum in a
      61-year-old man. Abdominal ultrasonography showed a mass to be hypoechoic with
      increased flow in color Doppler imaging. Dynamic contrast-enhanced computed
      tomography revealed a centripetal filling-in of the mass, located anterior to the
      left psoas muscle at the level of sacroiliac joint. On the basis of imaging
      features, preoperative diagnosis of hemangioma was considered and the mass was
      excised by laparoscopic method. Immunohistochemical studies were strongly
      positive for CD31 and CD34, and negative for calretinin, EMA, WT1, HMB45, Ki67,
      synaptophysin, and lymphatic endothelial cell marker D2-40. Histologically, the
      neoplasm was diagnosed as mixed capillary venous hemangioma.

PMID- 23533906
TI  - Lung cancer associated with neurofibromatosis type I.
AB  - Lung cancer associated with neurofibromatosis type I is considered very rare, and
      only a few case reports have been described in the literature. There is some
      evidence that a genetic linkage between neurofibromatosis and carcinogenesis in
      the lung may exist. We present a 42-year-old female, lifetime nonsmoker with a
      known history of neurofibromatosis type I, free of respiratory symptoms, who
      underwent a low-dose HRCT of the lungs to investigate any occult interstitial
      lung changes. A solitary ill-defined nodule of a ground-glass opacity was
      detected incidentally in the middle lobe with no associated lymphadenopathy or
      metastatic disease. Several thin-walled lung cysts were also seen in the lower
      lobes. Histological analysis of the nodule after middle lobectomy revealed well
      differentiated adenocarcinoma. The patient did not receive systemic chemotherapy
      or radiotherapy. She was free of disease on 18-month followup.

PMID- 23533907
TI  - Reactivation of Old Scars in an Elderly Man Revealing Lofgren's Syndrome.
AB  - Here, we report the case of a 55-year-old man with reactivation of old cutaneous
      scars associated with a febrile illness, episcleritis, polyarthralgias, erythema
      nodosum and hilar adenopathy. High-resolution computed tomography (HRCT) revealed
      right paratracheal, bilateral hilar, and subcarinal lymphadenopathy without any
      nodular densities in both lung fields. A scar biopsy revealed multiple
      noncaseating granulomas and confirmed the diagnosis of sarcoidosis. A short
      course of oral steroids led to regression of systemic symptoms, and the scars
      returned to baseline size. This patient represented a rare case of simultaneous
      Lofgren's syndrome and scar sarcoidosis.

PMID- 23533908
TI  - Colocolic intussusception in an older child: a rare case report and a literature
      review.
AB  - Intussusception is a common cause of intestinal obstruction and colicky abdominal
      pain in the children, particularly infants, the commonest being the ileocolic
      variety with colocolic variety being a very rare entity. We present a case of
      colocolic intussusception in a 13-year-old boy which is otherwise seen in adults,
      precipitated by colonic malignancies. The patient presented with acute abdominal
      pain and bleeding perrectum with obstipation for 7 days. Preoperative USG abdomen
      was normal, and abdominal X-rays showed multiple air fluid levels. Intraoperative
      findings included a polypoidal growth in the descending colon as the leading
      point with the formation of a colo-colic intussusception. Following reduction and
      segmental resection, histopathology reported mucinous adenocarcinoma of colon
      which is also a rarity in pediatric age group. This case has been compared with
      previous cases reported in the literature.

PMID- 23533909
TI  - Vertebral column metastases from an esthesioneuroblastoma: chemotherapy,
      radiation, and resection for recurrence with 15-year followup.
AB  - Esthesioneuroblastoma (ENB) is an uncommon aggressive malignant intranasal
      neoplasm that originates from neural crest cells of the olfactory epithelium.
      Although local invasion to the sinuses is common, spinal metastasis of ENB is
      rare with only 28 documented cases involving the spine spinal cord, or
      leptomeninges. We report a case of ENB with multiple drop metastases to the
      cervical and thoracic spine, and review the patient's disease, medical history,
      and multiple interventions during a span of 15 years following the initial
      cranial resection. Despite aggressive multiple surgical resections, radiation,
      and chemotherapy, the tumor had significant progression and recurrence. The
      literature is reviewed, followed by a discussion of the natural progression of
      the disease and various reported interventions. Although a combination of surgery
      with chemotherapy and radiation therapy has been recommended, no definitive
      management has been established for ENB. Further research is needed to determine
      decisive treatment for metastatic ENB to the spine.

PMID- 23533910
TI  - Remote Cerebellar Hemorrhage after Removal of a Supratentorial Glioma without
      Perioperative CSF Loss: A Case Report.
AB  - A 44-year-old man presented with the rare complication of remote cerebellar
      hemorrhage (RCH) after removal of a supratentorial glioma without the loss of a
      large volume of cerebrospinal fluid (CSF). He presented with severe headache,
      nausea, and vomiting for a few days, then he developed neurological deterioration
      including progressive disturbance of consciousness and left hemiparesis. Magnetic
      resonance imaging revealed a large tumor with intratumoral hemorrhage in the
      right frontal lobe that led to subfalcial and transtentorial herniation. The
      tumor was removed en bloc without excessive loss of CSF throughout the
      perioperative period. Although the level of consciousness remained unchanged from
      the preoperative level and no new neurological deficit was detected, routine
      postoperative computed tomography showed a bilateral RCH. Careful conservative
      therapy was provided and follow-up computed tomography demonstrated no further
      progression of hemorrhage. Compensatory acute engorgement of venous sinuses
      derived from the rapid decrease in intracranial pressure that occurred due to
      removal of the huge tumor might have caused cerebellar hemorrhagic venous
      infarction.

PMID- 23533911
TI  - Bilothorax: a bitter complication of liver surgery.
AB  - Bilothorax is a rare condition, mostly associated with surgery involving the
      biliary system or trauma. In this article a case of bilothorax secondary to liver
      surgery is reported, which recovered by pleural and abdominal drainage.
      Bilothorax should be considered as a cause of respiratory detoriation in patients
      with recent biliary or hepatic surgery.

PMID- 23533912
TI  - Small Bowel Injury in Peritoneal Encapsulation following Penetrating Abdominal
      Trauma.
AB  - Small bowel encapsulation is a rare entity which is usually found incidentally at
      autopsy. We report the first case of peritoneal encapsulation encountered
      serendipitously at laparotomy undertaken for penetrating abdominal trauma and
      review the literature on peritoneal encapsulation. We also compare this
      phenomenon to abdominal cocoon and sclerosing encapsulating peritonitis.

PMID- 23533913
TI  - An alternative technique for surgical management of poststernotomy osteomyelitis
      and reconstruction of the sternal defect.
AB  - Introduction. Sternal osteomyelitis with or without mediastinal infection is a
      severe and rare complication of median sternotomy. In this paper, an alternative
      technique for the reconstruction of sternal defects with the use of bilateral
      pectoralis major pedicled muscle flaps is presented. Case presentation. A 70-year
      old man with the diagnosis of poststernotomy osteomyelitis underwent
      reconstruction of his sternal defect with the use of bilateral pectoralis major
      muscle flaps. The patient had an uneventful recovery, and the physical
      examination revealed a normal range of motion for both upper limbs and sternal
      stability. Conclusion. The proposed technique incorporates a simple mobilization
      of the two pectoralis major muscles to be used as flaps to fill the sternal
      defect without the need for humeral detachment or a second cutaneous incision.
      Using this technique, a muscular implant is made that seals the dead space, which
      has no tension due to the presence of a second layer. Postoperative results are
      excellent, not only regarding infection and functionality but also from an
      aesthetic point of view.

PMID- 23533914
TI  - Adenomyoepithelioma with ductal carcinoma in situ: a case report and review of
      the literature.
AB  - Adenomyoepithelioma (AME) with microglandular adenosis-like growth pattern and
      superimposed ductal carcinoma in situ (DCIS) was identified in a 55-year-old
      female after biopsy of an atypical lesion identified through routine breast
      screening. A literature review reveals that this association has rarely been
      described.

PMID- 23533915
TI  - A Rare Coexistence of Retroperitoneal Pararenal Castleman's Disease with Focal
      Nodular Hyperplasia.
AB  - Castleman's disease is a distinct form of lymph node hyperplasia divided into a
      solitary and a multicentric type. The solitary type occurs most commonly in the
      mediastinum and is usually asymptomatic. We present a patient with Castleman's
      disease of the hyaline-vascular solitary type located in the retroperitoneum. The
      patient was a 38-year-old male, who presented to our hospital with fever. The
      imaging workup revealed a retroperitoneal mass, measuring 4 * 6 cm, located
      lateral to the aorta, inferior to the left renal artery and vein, and posterior
      to the left testicular vein. At workup, a solid hepatic lesion, 3 cm in diameter,
      located in the left lobe of the liver, segment IV, was also identified. Both
      lesions were surgically excised. The retroperitoneal tumor had the features of
      angiofollicular hyperplasia (Castleman's disease), hyaline-vascular type, whereas
      a diagnosis of focal nodular hyperplasia was made for the hepatic lesion. The
      patient is well at fourty months followup postoperatively. Surgical excision is
      the treatment of choice for unifocal Castleman's disease.

PMID- 23533916
TI  - Unilateral Giant Varicocele Mimicking Inguinal Hernia Resulting from
      Portosystemic Shunt without Evidence of Portal Hypertension: An Unusual Case
      Report.
AB  - Isolated giant varicocele has been reported with portal hypertension that results
      in abnormal communication between portal venous system and testicular vein venous
      system resulting in retrograde backflow of blood into the testicular venous
      system which leads to varicosity of the pampiniform plexuses. 65-year-old male
      with no past medical or surgical history presented to us with soft inguinoscrotal
      swelling that disappears on lying down mimicking inguinal hernia. Clinical
      examination revealed soft inguionoscrotal swelling that disappears on pressure.
      Ultrasonography revealed varicosity of pampiniform plexus, and CT angiography to
      trace the extent of the varicosity revealed abnormal communication of right
      testicular vein with superior mesenteric vein. There was no evidence of any
      portal hypertension; the cause of the portosystemic shunt remains obscure, and it
      might be a salvage pathway for increasing portal pressure. The case is noteworthy
      for its rare presentation and abnormal communication with portal venous system in
      the absence of evidence of portal hypertension.

PMID- 23533917
TI  - An unusual left upper quadrant mass: a bronchopulmonary foregut malformation.
AB  - We report a case of a lady who presented with epigastric discomfort. Physical
      examination revealed a large left upper quadrant mass filling the left upper
      quadrant. Following extensive preoperative evaluation, she underwent resection of
      this 9 * 10 * 11 centimeter mass with en bloc excision of a portion of the left
      hemidiaphragm. She made an uneventful postoperative recovery. Histopathology
      revealed a bronchopulmonary foregut malformation with pulmonary sequestration.
      This developmental anomaly of the foregut typically occurs in the thoracic
      cavity; however, it can occur below the diaphragm. Herein we report a case and a
      detailed review of the embryology, clinical features, and management of these
      extremely rare clinical entities.

PMID- 23533918
TI  - Anorectal Injuries due to Foreign Bodies: Case Reports and Review of the
      Management Options.
AB  - Anorectal injuries due to autoerotic activity with rectal foreign bodies were
      identified in four male patients. The objects were bottle in one patient, glasses
      in two patients, and showerhead in one patient. Foreign bodies were extracted
      within lithotomy position after anal dilatation, under general anesthesia in 3
      patients. One patient presented with peritoneal irritation and had a diagnosis of
      rectal perforation. He underwent transanal rectal repair with proximal fecal
      diversion. In this paper we described 4 patients who had anorectal injuries due
      to autoerotic activity with foreign bodies and reviewed the management options in
      literature.

PMID- 23533919
TI  - Late recurrence of benign multicystic peritoneal mesothelioma complicated with an
      incisional hernia.
AB  - Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease arising from
      the peritoneal mesothelium. Here, we report a 57-year-old woman admitted to our
      unit with an incisional hernia fifteen years later following her first operation
      due to BMPM. Computerized tomography demonstrated a cystic appearing mass with
      intraabdominal extension in hernia sac. The patient underwent en bloc resection
      of the mass and hernia repair. An immunohistochemical analysis of the mass
      confirmed the recurrence of BMPM. Our case supports that BMPM has slowly
      progressive nature and can recur with complicated incisional hernia long time
      after primary resection. Diagnosis and long-term followup are crucial for
      clarifying the characteristics of this disease.

PMID- 23533920
TI  - Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation
      for cerebral palsy: a case report.
AB  - Cerebral palsy is the most common motor disability in childhood. In current
      paper, we first report our clinical data regarding administration of umbilical
      cord mesenchymal stem cells (MSCs) transplantation in treatment of cerebral
      palsy. A 5-year-old girl with cerebral palsy was treated with multiple times of
      intravenous and intrathecal administration of MSCs derived from her young sister
      and was followed up for 28 months. The gross motor dysfunction was improved.
      Other benefits included enhanced immunity, increased physical strength, and
      adjusted speech and comprehension. Temporary low-grade fever was the only side
      effect during the treatment. MSCs may be a safe and effective therapy to improve
      symptoms in children with cerebral palsy.

PMID- 23533921
TI  - Acute renal failure and volume overload syndrome secondary to a femorofemoral
      arteriovenous fistula angioplasty in a kidney transplant recipient.
AB  - Experimental and clinical studies analyzing the impact of AVF on cardiovascular
      and renal parameters, as well as outcomes, in kidney transplant recipients are
      lacking. On the other hand, it is not known whether AVF ligation after
      transplantation modifies hemodynamic parameters and kidney function. We report a
      case of a renal transplant recipient who developed an acute congestive heart
      failure accompanied by renal failure, which were triggered by femorofemoral AVF
      angioplasty. Prompt AVF ligation rapidly reversed clinical symptoms and
      normalized cardiac and renal functions. This paper illustrates the potential
      deleterious consequences of high-output AVF after kidney transplantation and
      raises considerations regarding the impact of the fistula on cardiac status and
      kidney function after kidney transplantation and, consequently, the management
      AVF after transplantation.

PMID- 23533922
TI  - Spontaneous reattachment of a posteriorly dislocated endothelial graft: a case
      report.
AB  - A thirty-year-old Chinese man with a history of severe trauma to his right eye,
      with secondary sectoral aniridia and multiple operations including intraocular
      lens insertion more than fifteen years ago, underwent an uneventful Descemet's
      Stripping Automated Endothelial Keratoplasty (DSAEK) for his pseudophakic bullous
      keratopathy in a tertiary hospital in Hong Kong. The nature of his previous
      operations was unknown to the surgeon at the time of transplant. On postoperative
      day one, the graft was not present in the anterior chamber. Fundal view was
      limited because of corneal oedema. B-scan ultrasonography could not detect any
      definite presence of a donor button in the posterior segment as gas was present
      in the vitreous cavity. The patient was instructed to lie prone full time, and on
      postoperative day three, the graft was found to be reattached to the stroma with
      spontaneous resolution of corneal oedema, indicating restoration of pump function
      of endothelium graft. This is the first case of spontaneous reattachment of a
      posteriorly dislocated endothelial graft without surgical intervention or
      abandonment of the grafted endothelial button.

PMID- 23533923
TI  - Ligation of left renal vein for spontaneous splenorenal shunt to prevent portal
      hypoperfusion after orthotopic liver transplantation.
AB  - We report a case of recovered portal flow by ligation of the left renal vein on
      the first postoperative day after orthotopic liver transplantation of a 54-year
      old female with alcoholic liver cirrhosis, chronic kidney failure, and
      spontaneous splenorenal shunt. After reperfusion, Doppler ultrasonography showed
      almost total diversion of the portal flow into the existing splenorenal shunt,
      but because of severe coagulopathy and diffuse bleeding, ligation of the shunt
      was not attempted. A programmed relaparotomy was performed on the first
      postoperative day, and the left renal vein was ligated just to the left of the
      inferior vena cava. Portal flows subsequently increased to 37 cm/sec, and the
      patient presented a good and stable liver function. We conclude that patients
      with known preoperative splenorenal shunts should be closely monitored, and if
      the portal flow becomes insufficient, ligation of the left renal vein should be
      attempted in order to optimize the portal perfusion of the liver.

PMID- 23533924
TI  - Urinary frequency as a presentation of bulky malignant lymphoma in the pelvis.
AB  - Malignant lymphomas may originate from any area of the body and cause a variety
      of symptoms. However, a malignant lymphoma causing urinary symptoms is uncommon.
      We report a unique case of a 77-year-old woman who presented with a persistent
      pollakiuria. Radiographic imaging showed a large pelvic mass (13 * 13 * 11 cm)
      remarkably compressing and invading the bladder wall and accompanied with
      bilateral hydronephrosis. Urinary cytology revealed malignant lymphoma, and a
      final diagnosis of malignant lymphoma was made on the basis of transvaginal
      needle biopsy. Urinary cytology facilitated the definite diagnosis, following
      which we initiated a rapid and successful treatment with cyclophosphamide,
      doxorubicin, vincristine, and prednisone with rituximab.

PMID- 23533925
TI  - Metachronous occurrence of triple malignancies of kidneys, prostate, and breast.
      A case report and review of the literature.
AB  - Multiple consecutive cancers involving different organs in a male individual are
      presented. Case Presentation. Herein, we present a rare case of primary right
      renal cell carcinoma (RCC), in which two different organ malignancies of prostate
      and breast were occurred consecutively. After proper treatment of each organ
      tumor, the patient experienced metachronous occurrence of its final tumor in his
      remained left kidney as left side RCC. Discussions. Multiple primary cancers are
      defined as occurrence of two or more malignancies, synchronous or metachronous,
      in different organs without any relation to each other. For primary and secondary
      tumors of the male genitourinary system, the most common occurrence was tumors of
      bladder and prostate followed by tumors of the kidney. Our case was a rare
      presentation of consecutive occurrence of multiple organ tumors: right side RCC,
      adenocarcinoma of prostate, and ductal cell carcinoma of the left breast,
      followed by left side RCC. Conclusions. In any case of primary malignancy of any
      organ, not only primary tumor recurrence but also tumoral growth of other
      nonrelated organs should be evaluated, especially in high risk patients or
      patients with positive familial history.

PMID- 23533926
TI  - Primary obstructive megaureter with giant ureteral stone: a case report.
AB  - A 19-year-old male patient was admitted with flank pain, which had lasted
      intermittently for four years. In X-ray, there was a radiopacity with a dimension
      of 6 * 4 cm on the left pelvic bone. Intravenous pyelography revealed a huge left
      megaureter with a stone in the lower end and grade V hydronephrosis. A left
      ureterolithotomy, left nipple ureteroneocystostomy, and psoas hitch operation was
      performed. A voiding cystourethrogram taken three months after the operation
      showed no reflux, and in IVP there was reduced dilatation of the collecting
      system when compared to the ureter before the operation.

PMID- 23533927
TI  - Metachronous periadrenal Fatty tissue metastasis from contralateral renal cell
      carcinoma.
AB  - Contralateral adrenal metastases from renal cell carcinomas are not commonly
      seen. To our knowledge, we are presenting the first case of extraadrenal
      metastasis in the English literature, from the contralateral RCC 6 months after
      radical nephrectomy. Patient was treated with robotic right adrenalectomy for
      continuous growing of a de novo right adrenal mass of 6 * 4 * 3 cm in diameter.
      Tissue between vena cava, renal capsule, and inferior diaphragmatic surface was
      removed en block. Pathological evaluation revealed renal cell carcinoma within
      the fatty tissue abutting the adrenal capsule from outside with negative surgical
      margins. Our experience dictates that removing adrenal tissue only after
      identifying the adrenal borders may sometimes result in insufficient tumor
      removal. Therefore, adrenal containing tissue within the anatomic boundaries
      should be removed en block, if surgical removal is planned for metachronous tumor
      metastasis in the treatment of renal cell carcinoma.

PMID- 23533929
TI  - A congenital anterior urethrocutaneous fistula in a boy whose mother was exposed
      to ionizing radiations: case report and literature review.
AB  - Anterior congenital urethrocutaneous fistula is a rare anomaly that may present
      in an isolated fashion or in association with other anomalies of the genital
      urinary tract or anorectal malformations. A case of congenital anterior
      urethrocutaneous fistula nonassociated with other congenital anomalies in a 3
      year-old male whose mother has been exposed to Chernobyl's nuclear fallout is
      described. The patient was successfully operated with no recurrence. We report a
      review of the literature about etiology and surgical strategy including the role
      of ionizing radiations. The congenital anterior urethrocutaneous fistula
      represents a rare malformation. The etiopathogenesis is unknown.

PMID- 23533928
TI  - Small cell prostate carcinoma: a case report and review of the literature.
AB  - Small cell prostate cancer constitutes less than 1% of all prostate cancers and
      has a poor prognosis. A 60-year-old male patient presented with dysuria,
      pollakiuria, and nocturia of about 1-year duration.The total PSA level at
      admission was 47.50 ng/mL. The prostate needle biopsy result was reported as
      adenocarcinoma Gleason 5 + 3. The patient underwent transurethral prostate
      resection (TUR-P) and bilateral orchiectomy. The TUR-P pathology result was
      consistent with small cell neuroendocrine carcinoma. He was offered systemic
      chemotherapy but refused it. Examinations and tests at the third postoperative
      month showed diffuse liver metastasis and vertebral bone metastasis. He died at
      the 6 months after surgery.

PMID- 23533930
TI  - The role of laparoscopic nephrectomy in pediatric xanthogranulomatous
      pyelonephritis: a case report.
AB  - Xanthogranulomatous pyelonephritis (XGP) is a rare chronic renal infection
      characterized by the destruction of renal parenchyma. Traditional treatment
      involves open radical nephrectomy, which is challenging due to the inflammatory
      process associated with XGP. More recently, laparoscopic nephrectomy has been
      employed successfully in adult XGP. We present a case of a six-year-old female
      child with XGP who was successfully treated by laparoscopic nephrectomy with
      minor complications. Our case demonstrates the safety and feasibility of
      laparoscopic nephrectomy for childhood XGP, indicating that it should be
      considered a management option in such cases.

PMID- 23533931
TI  - Postoperative Complications Leading to Death after Coagulum Pyelolithotomy in a
      Tetraplegic Patient: Can We Prevent Prolonged Ileus, Recurrent Intestinal
      Obstruction due to Adhesions Requiring Laparotomies, Chest Infection Warranting
      Tracheostomy, and Mechanical Ventilation?
AB  - A 22-year-old male sustained C-6 tetraplegia in 1992. In 1993, intravenous
      pyelography revealed normal kidneys. Suprapubic cystostomy was performed. He
      underwent open cystolithotomy in 2004 and 2008. In 2009, computed tomography
      revealed bilateral renal calculi. Coagulum pyelolithotomy of left kidney was
      performed. Pleura and peritoneum were opened. Peritoneum could not be closed.
      Following surgery, he developed pulmonary atelectasis; he required tracheostomy
      and mechanical ventilation. He did not tolerate nasogastric feeding. CT of
      abdomen revealed bilateral renal calculi and features of proximal small bowel
      obstruction. Laparotomy revealed small bowel obstruction due to dense
      inflammatory adhesions involving multiple small bowel loops which protruded
      through the defect in sigmoid mesocolon and fixed posteriorly over the area of
      previous intervention. All adhesions were divided. The wide defect in mesocolon
      was not closed. In 2010, this patient again developed vomiting and distension of
      abdomen. Laparotomy revealed multiple adhesions. He developed chest infection and
      required ventilatory support again. He developed pressure sores and depression.
      Later abdominal symptoms recurred. This patient's general condition deteriorated
      and he expired in 2011. Conclusion. Risk of postoperative complications could
      have been reduced if minimally invasive surgery had been performed instead of
      open surgery to remove stones from left kidney. Suprapubic cystostomy predisposed
      to repeated occurrence of stones in urinary bladder and kidneys. Spinal cord
      physicians should try to establish intermittent catheterisation regime in
      tetraplegic patients.

PMID- 23533932
TI  - Self-inflicted male bladder foreign body: its endoscopic removal using a rigid
      cystoscope and a suprapubic forceps.
AB  - Introduction. Herein we present an interesting technique for the removal of
      bladder foreign body (BFB) in which a combination of endoscopic and suprapubic
      cystostomy was used. Case Presentation. The patient was a case of illicit drug
      abuser who self-introduced an electrical wire into his bladder. After its failed
      cystoscopic removal, the foreign body was removed suprapubically without open
      bladder surgery. Discussions. Bladder foreign bodies are not uncommon. Based on
      the literature review, mainly open surgeries were used for their treatment. Using
      of our less invasive technique is a good way for escaping from open cystostomy.
      Conclusion. Endoscopic removal of the bladder foreign bodies is possible without
      any need for open bladder surgery.

PMID- 23533933
TI  - A rare metastasis to the bladder.
AB  - Primary bladder cancer is the fifth most common malignancy but secondary
      malignancies of the bladder are rare. Distinguishing primary adenocarcinomas of
      the bladder from secondary adenocarcinomas is difficult and relies on
      immunohistochemical staining. Prostate, colorectal, breast, and lung all can
      produce metastatic adenocarcinomas to the bladder. Further management of the
      malignancy varies depending on the source, thus making proper diagnosis critical.
      We present only the fifth documented case of metastatic adenocarcinoma of the
      lung to bladder and performed a review of the literature.

PMID- 23533934
TI  - Hepatitis C transmission after prostate biopsy.
AB  - Prostate biopsy is a current and well-codified procedure; antibiotic prophylaxis
      and rectal enema limit the risk of infection. To date, there has been no reported
      viral transmission between patients due to a contaminated ultrasound probe. In
      this study, we report the case of a patient who contracted the hepatitis C virus
      after transrectal prostate biopsy as part of an individual screening for prostate
      cancer.

PMID- 23533935
TI  - Paratesticular liposarcoma: a case report and review of the literature.
AB  - Introduction. Liposarcoma is a rare pathological entity. By far it is the most
      common histological subtype of genitourinary sarcomas in adults. Approximately
      two hundred cases were reported in the literature. We are hereby presenting a
      case with a typical clinical scenario of paratesticular liposarcoma. Case report.
      A 75-year-old gentleman presented with a painless right hemiscrotal swelling that
      was progressively increasing in size over the last 6 years. Testicular tumour
      markers were negative. Imaging showed a heterogenous mass with fat component.
      Subsequently he underwent wide local excision that included the paratesticular
      mass along with the right testicle and all right inguinal canal contents up to
      the deep inguinal ring with the sparing of right illioinguinal nerve.
      Histopathological examination showed a well differentiated liposarcoma of the
      spermatic cord. He remained recurrence-free so far after 18 months of followup.
      Conclusion. Radical orchidectomy with wide local excision comprises the
      cornerstone of treatment of paratesticular liposarcoma. Due to the rarity of the
      disease there is no definite universal consensus of opinion as regards the role
      of radiotherapy and chemotherapy.

PMID- 23533936
TI  - Rupture in polycystic kidney disease presented as generalized peritonitis with
      severe sepsis: a rare case report.
AB  - Recurrent upper urinary tract (renal) infections have been reported to be
      frequent in patients with autosomal dominant polycystic kidney disease and often
      difficult to treat. Female preference and enteric organism predominance suggest
      that these renal infections are acquired to retrograde from the lower urinary
      tract. We encountered a rare case of bilateral polycystic kidneys with
      spontaneous intraperitoneal rupture of multiple infected renal cysts causing
      generalized peritonitis leading to severe sepsis with multiorgan failure. The
      patient is successfully managed with nephrectomy followed by prolonged supportive
      care in intensive care unit.

PMID- 23533937
TI  - Fatal aortic dissection in a patient with giant cell arteritis: a case report and
      review of the literature.
AB  - Giant cell arteritis may lead to catastrophic, large-vessel complications from
      chronic vascular wall inflammation without prompt diagnosis and treatment. We
      describe a rare case of acute aortic dissection without preceding aneurysm
      secondary to histologically confirmed giant cell arteritis (GCA) in an 85-year
      old female with a four-year history of polymyalgia rheumatica and temporal
      arteritis diagnosed per biopsy six months prior to presentation. The literature
      is reviewed and the clinical implications of this case are discussed.

PMID- 23533938
TI  - Recurrent Vertigo: Is it Takayasu's Arteritis?
AB  - Takayasu's arteritis (TA) is a chronic, idiopathic, inflammatory disease, that is
      more common in females and Asian countries. A 38-year-old female presented with
      recurrent vertigo. Detailed examination revealed discrepancies in peripheral
      pulses and raised blood pressure in bilateral lower limbs. Possibility of
      vasculitis involving arch of aorta or its branches was kept. Investigations were
      suggestive of Takayasu's arteritis, and noncontrast tomographic scanning (NCCT)
      of head showed B/L parietal infarcts. The disease is itself uncommon, and the
      presentation with vertigo only is rare. In this case vertigo may be due to
      Takayasu's arteritis itself or due to bilateral parietal infarcts.

PMID- 23533939
TI  - Atrial fibrillation.

PMID- 23533941
TI  - Heart rate variability in children with tricyclic antidepressant intoxication.
AB  - The aim of this study was to evaluate HRV in children requiring intensive care
      unit stays due to TCA poisoning between March 2009 and July 2010. In the time
      domain nonspectral evaluation, the SDNN (P < 0.001), SDNNi (P < 0.05), RMSDD (P <
      0.01), and pNN50 (P < 0.01) were found to be significantly lower in the TCA
      intoxication group. The spectral analysis of the data recorded during the first 5
      minutes after intensive care unit admission showed that the values of the nLF (P
      < 0.05) and the LF/HF ratio (P = 0.001) were significantly higher in the TCA
      intoxication group, while the nHF (P = 0.001) values were significantly lower.
      The frequency-domain spectral analysis of the data recorded during the last 5
      minutes showed a lower nHF (P = 0.001) in the TCA intoxication group than in the
      controls, and the LF/HF ratio was significantly higher (P < 0.05) in the
      intoxication group. The LF/HF ratio was higher in the seven children with
      seizures (P < 0.001). These findings provided us with a starting point for the
      value of HRV analysis in determining the risk of arrhythmia and convulsion in TCA
      poisoning patients. HRV can be used as a noninvasive testing method in
      determining the treatment and prognosis of TCA poisoning patients.

PMID- 23533940
TI  - P2Y12 Receptor Inhibitors in Acute Coronary Syndromes: What Is New on the
      Horizon?
AB  - Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor represents
      the cornerstone therapy for patients with acute coronary syndromes or undergoing
      percutaneous interventions, leading to a reduction of subsequent ischemic events.
      Variable response to clopidogrel has received close attention, and
      pharmacokinetic, pharmacodynamic, and pharmacogenomic factors have been
      identified as culprits. This led to the introduction of newer, potentially safer,
      and more effective antiplatelet agents (prasugrel and ticagrelor). Additionally,
      several point-of-care assays of platelet function have been developed in recent
      years to rapidly screen individuals on antiplatelet therapy. While the routine
      use of platelet function testing is uncertain and not currently recommended, it
      may be useful in instances when the degree of platelet inhibition may be
      uncertain such as high-risk patients undergoing percutaneous coronary
      intervention or when there may be a suspected pharmacodynamic interaction with
      other drugs. The current paper focuses on the P2Y12 receptor inhibitors and their
      pharmacogenetics and indications in patients with acute coronary syndromes or
      receiving percutaneous coronary interventions as well as the applicability of
      platelet function testing in this clinical context.

PMID- 23533942
TI  - Chronobiological analysis of blood pressure in a patient with atrial fibrillation
      at the development of heart failure and its therapeutic and surgical treatment.
AB  - Dynamics of blood pressure (BP) and heart rate (HR) was traced by automatic
      monitoring every 30 min uninterruptedly along several months in a patient
      suffering from combined atrial fibrillation and heart failure during the
      development of disease and its therapeutic and surgical treatment (pacemaker
      implanting and atrioventricular ablation). Analyses of spectral components as
      well as signal's shape revealed instabilities in circadian and semicircadian
      parameters. A new approach for signal's form description without using cosine
      approximation is suggested. The meaning that referring a patient as dipper, night
      peaker, or nondipper might be useful at choosing tactics of his treatment is
      impugned, because all these "types" can transform themselves in the same person
      in few days. Optimization timing of treatment provides better results if not the
      "types" of daily profile would be taken to account but the real form of the BP
      signal and timing its first and second derivatives.

PMID- 23533943
TI  - Brachial-ankle pulse wave velocity is the only index of arterial stiffness that
      correlates with a mitral valve indices of diastolic dysfunction, but no index
      correlates with left atrial size.
AB  - The objective of this study was to determine the optimal assessment of arterial
      stiffness that relates to diastolic dysfunction. Forty-one patients had
      measurements of brachial-ankle pulse wave velocity (baPWV), carotid-femoral pulse
      wave velocity (cfPWV), ankle brachial index (ABI), pulse pressure (PP), and
      augmentation index (AIx). Diastolic dysfunction was evaluated by
      echocardiographic indices of the ratio of the peak early diastolic mitral valve
      velocity and the peak late diastolic velocity (E/A ratio), left atrial diameter,
      and left atrial volume indexes. There was a significant (P < 0.05) correlation
      between baPWV and E/A ratio with an inverse relationship indicating that higher
      arterial stiffness was associated with greater diastolic dysfunction. In
      contrast, there was no significant correlation between E/A ratio and cfPWV, PP,
      ABI, or AIx. After multivariate analysis, the relationship between baPWV and E/A
      ratio remained significant (P < 0.05), independent of age and systolic blood
      pressure (BP). There were no correlations between any index of vascular stiffness
      and left atrial dimension or volume. In summary, baPWV correlates with diastolic
      dysfunction, independent of a patient's age and BP and is a better indicator of
      diastolic dysfunction than other indicators of arterial stiffness. baPWV has the
      utility of infering the presence of left ventricular diastolic dysfunction.

PMID- 23533944
TI  - Longitudinal Changes in the Government-Certified Index Stage and Requisite Costs
      for Long-Term Care Insurance System among the Community-Dwelling Demented Elderly
      in Japan.
AB  - Background. A new public long-term care (LTC) insurance was launched in 2000 in
      Japan. However, there have been few studies involving factors that increase LTC
      costs of demented subjects; no follow-up studies involving the Government
      Certified Index (GCI) and requisite costs related to the causes of dementia.
      Method. An epidemiological survey was conducted in a rural area in Japan in 1999,
      and 271 subjects were diagnosed as dementia patients. Age, sex, mini-mental state
      examination, clinical dementia rating, activity of daily living, causes of
      dementia, and coexisting physical disease were confirmed. After the LTC insurance
      has been launched, we tracked the GCI stages and payment amounts every month for
      8 years. Result. 209 subjects were certified to be eligible for LTC insurance;
      however, 13 did not receive any payment. Only 49 out of 209 were alive after the
      follow-up period. The most common cause of dementia was Alzheimer's disease (AD),
      followed by vascular dementia (VaD). There was no significant difference between
      the mortality rates of the two groups. VaD subjects required higher costs than AD
      subjects in the total certified period and in GCI stage 5. Conclusion. Our
      results indicate that causes of dementia can have an impact on the requisite
      costs for the LTC insurance.

PMID- 23533945
TI  - Pathogen-driven selection in the human genome.
AB  - Infectious diseases and epidemics have always accompanied and characterized human
      history, representing one of the main causes of death. Even today, despite
      progress in sanitation and medical research, infections are estimated to account
      for about 15% of deaths. The hypothesis whereby infectious diseases have been
      acting as a powerful selective pressure was formulated long ago, but it was not
      until the availability of large-scale genetic data and the development of novel
      methods to study molecular evolution that we could assess how pervasively
      infectious agents have shaped human genetic diversity. Indeed, recent evidences
      indicated that among the diverse environmental factors that acted as selective
      pressures during the evolution of our species, pathogen load had the strongest
      influence. Beside the textbook example of the major histocompatibility complex,
      selection signatures left by pathogen-exerted pressure can be identified at
      several human loci, including genes not directly involved in immune response. In
      the future, high-throughput technologies and the availability of genetic data
      from different populations are likely to provide novel insights into the
      evolutionary relationships between the human host and its pathogens. Hopefully,
      this will help identify the genetic determinants modulating the susceptibility to
      infectious diseases and will translate into new treatment strategies.

PMID- 23533947
TI  - Osteoporosis self-assessment tool performance in a large sample of postmenopausal
      women of mendoza, Argentina.
AB  - The Osteoporosis Self-assessment Tool (OST) is a clinical instrument designed to
      select patients at risk of osteoporosis, who would benefit from a bone mineral
      density measurement. The OST only takes into account the age and weight of the
      subject. It was developed for Asian women and later validated for European and
      North American white women. The performance of the OST in a sample of 4343 women
      from Greater Mendoza, a large metropolitan area of Argentina, was assessed. Dual
      X-ray absorptiometry (DXA) scans of lumbar spine and hip were obtained. Patients
      were classified as either osteoporotic (N = 1830) or nonosteoporotic (n = 2513)
      according to their lowest T-score at any site. Osteoporotic patients had lower
      OST scores (P < 0.0001). A receiver operating characteristic (ROC) curve showed
      an area under the curve of 71% (P < 0.0001), with a sensitivity of 83.7% and a
      specificity of 44% for a cut-off value of 2. Positive predictive value was 52%
      and negative predictive value was 79%. The odds ratio for the diagnosis of
      osteoporosis was 4.06 (CI95 3.51 to 4.71; P < 0.0001). It is concluded that the
      OST is useful for selecting postmenopausal women for DXA testing in the studied
      population.

PMID- 23533946
TI  - Infiltration of proinflammatory m1 macrophages into the outer retina precedes
      damage in a mouse model of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a major cause of blindness in the
      developed world. Oxidative stress and inflammation are implicated in AMD, but
      precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD
      associated lipid peroxidation product. We previously demonstrated that mice
      immunized with CEP-modified albumin developed AMD-like degenerative changes in
      the outer retina. Here, we examined the kinetics of lesion development in
      immunized mice and the presence of macrophages within the interphotoreceptor
      matrix (IPM), between the retinal pigment epithelium and photoreceptor outer
      segments. We observed a significant and time-dependent increase in the number of
      macrophages in immunized mice relative to young age-matched controls prior to
      overt pathology. These changes were more pronounced in BALB/c mice than in
      C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the
      M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were
      immunized, macrophages were not present in the IPM and no retinal lesions were
      observed, suggesting a deleterious role for these cells in our model. This work
      provides mechanistic evidence linking immune responses against oxidative damage
      with the presence of proinflammatory macrophages at sites of future AMD and
      experimentally demonstrates that manipulating immunity may be a target for
      modulating the development of AMD.

PMID- 23533948
TI  - Bone mineral density and body composition of adult premenopausal women with three
      levels of physical activity.
AB  - Weight-bearing and resistance physical activities are recommended for
      osteoporosis prevention, but it is unclear whether an intensity level above
      current recommendations has a positive effect on adult premenopausal women. Body
      composition and bone mineral density (BMD) by DXA were compared in three groups
      of women as follows: Sedentary, Maintenance exercise, and federated Sport Team (n
      = 16 for each group). Physical activity was estimated from the International
      Physical Activity Questionnaire (IPAQ). The groups did not differ in age, height,
      weight, or body mass index. Bone mineral content and non-fat soft tissue mass
      were higher and fat mass was lower in the Sport Team group than in the other
      groups. The same was true for BMD of total skeleton, lumbar spine, femoral neck,
      and total hip. A test for linear trend of body composition and BMD showed
      significant results when including all three groups. Simple and multiple
      regression analyses showed significant associations between physical activity
      level (or alternatively, years of participation in programmed physical activity)
      and bone mass measures at all sites except for the middle third of radius. It is
      concluded that a level of physical activity higher than that usually recommended
      benefits bone health in adult premenopausal women.

PMID- 23533949
TI  - Serum resistin and insulin-like growth factor-1 levels in patients with
      hypothyroidism and hyperthyroidism.
AB  - Introduction. The aim of this study was to evaluate the serum levels of resistin
      and insulin-like growth factor-1 (IGF-1) and and also the potential relationship
      between thyroid function and levels of resistin and IGF-1 in hypothyroid and
      hyperthyroid patients. Methods. Fifteen cases of hypothyroid (HT), 16 of
      subclinically hypothyroid (SCHT), 15 of hyperthyroid (HrT), 15 of subclinically
      hyperthyroid (SCHrT), and 17 healthy individuals have been included in the study.
      Serum resistin levels were measured using enzyme-linked immunosorbent assay and
      IGF-1 and thyroid stimulating hormone (TSH) levels by chemiluminescence method.
      Results. Resistin levels in total HT group were significantly higher than in
      controls (12.66 +/- 6.04 and 8.45 +/- 2.90 ng/mL, resp.). In SCHrT subgroup
      resistin levels were significantly higher than those of controls (14.88 +/- 7.73
      and 8.45 +/- 2.90 ng/mL, resp.). IGF-1 levels were significantly lower in total
      HT than in total HrT and control groups (117.22 +/- 52.03, 155.17 +/- 51.67, and
      184.00 +/- 49.73 ng/mL, resp.). Furthermore IGF-1 levels in HT subgroup were
      significantly lower compared to controls (123.70 +/- 44.03 and 184 +/- 49.73
      ng/mL, resp.). In SCHT subgroup IGF-1 levels were significantly lower than those
      of control and SCHrT groups (111.11 +/- 59.35, 184.00 +/- 49.73, and 166.60 +/-
      47.87 ng/mL, resp.). There were significant correlations between IGF-1 and TSH in
      HT subgroup and between resistin and TSH in total HrT group. Conclusion. It was
      concluded that increased resistin levels are directly related to thyroid
      dysfunction, and GH/IGF-1 axis is influenced in clinically or subclinically
      hypothyroidism patients.

PMID- 23533950
TI  - Thyroid hormone and tissue repair: new tricks for an old hormone?
AB  - Although the role of thyroid hormone during embryonic development has long been
      recognized, its role later in adult life remains largely unknown. However,
      several lines of evidence show that thyroid hormone is crucial to the response to
      stress and to poststress recovery and repair. Along this line, TH administration
      in almost every tissue resulted in tissue repair after various injuries including
      ischemia, chemical insults, induction of inflammation, or exposure to radiation.
      This novel action may be of therapeutic relevance, and thyroid hormone may
      constitute a paradigm for pharmacologic-induced tissue repair/regeneration.

PMID- 23533951
TI  - Malariometric Indices among Nigerian Children in a Rural Setting.
AB  - Malaria contributes to high childhood morbidity and mortality in Nigeria. To
      determine its endemicity in a rural farming community in the south-south of
      Nigeria, the following malariometric indices, namely, malaria parasitaemia,
      spleen rates, and anaemia were evaluated in children aged 2-10 years. This was a
      descriptive cross-sectional survey among school-age children residing in a rubber
      plantation settlement. The children were selected from six primary schools using
      a multistaged stratified cluster sampling technique. They were all examined for
      pallor, enlarged spleen, or liver among other clinical parameters and had blood
      films for malaria parasites. Of the 461 children recruited, 329 (71.4%) had
      malaria parasites. The prevalence of malaria parasitaemia was slightly higher in
      the under fives than that of those >=5 years, 76.2% and 70.3%, respectively.
      Splenic enlargement was present in 133 children (28.9%). The overall prevalence
      of anaemia was 35.7%. Anaemia was more common in the under-fives (48.8%) than in
      those >=5 years (32.8%). The odds of anaemia in the under fives were
      significantly higher than the odds of those >=5 years (OR = 1.95 [1.19-3.18]).
      Malaria is highly endemic in this farming community and calls for intensification
      of control interventions in the area with special attention to school-age
      children.

PMID- 23533952
TI  - Slow Down and Concentrate: Time for a Paradigm Shift in Fall Prevention among
      People with Parkinson's Disease?
AB  - Introduction. We know little about how environmental challenges beyond home
      exacerbate difficulty moving, leading to falls among people with Parkinson's
      (PwP). Aims. To survey falls beyond home, identifying challenges amenable to
      behaviour change. Methods. We distributed 380 questionnaires to PwP in Southern
      England, asking participants to count and describe falls beyond home in the
      previous 12 months. Results. Among 255 responses, 136 PwP (diagnosed a median 8
      years) reported falling beyond home. They described 249 falls in detail, commonly
      falling forward after tripping in streets. Single fallers (one fall in 12 months)
      commonly missed their footing, walking, or changing position and recovered to
      standing alone or with unfamiliar help. Repeat fallers (median falls, two)
      commonly felt shaken or embarrassed and sought medical advice. Very frequent
      fallers (falling at least monthly; median falls beyond home, six) commonly fell
      backward, in shops and after collapse but often recovered to standing alone.
      Conclusion. Even independently active PwP who do not fall at home may fall beyond
      home, often after tripping. Falling beyond home may result in psychological
      and/or physical trauma (embarrassment if observed by strangers and/or injury if
      falling backwards onto a hard surface). Prevention requires vigilance and
      preparedness: slowing down and concentrating on a single task might effectively
      prevent falling.

PMID- 23533953
TI  - Recurrent falls in Parkinson's disease: a systematic review.
AB  - Most people with Parkinson's disease (PD) fall and many experience recurrent
      falls. The aim of this review was to examine the scope of recurrent falls and to
      identify factors associated with recurrent fallers. A database search for journal
      articles which reported prospectively collected information concerning recurrent
      falls in people with PD identified 22 studies. In these studies, 60.5% (range 35
      to 90%) of participants reported at least one fall, with 39% (range 18 to 65%)
      reporting recurrent falls. Recurrent fallers reported an average of 4.7 to 67.6
      falls per person per year (overall average 20.8 falls). Factors associated with
      recurrent falls include: a positive fall history, increased disease severity and
      duration, increased motor impairment, treatment with dopamine agonists, increased
      levodopa dosage, cognitive impairment, fear of falling, freezing of gait,
      impaired mobility and reduced physical activity. The wide range in the frequency
      of recurrent falls experienced by people with PD suggests that it would be
      beneficial to classify recurrent fallers into sub-groups based on fall frequency.
      Given that there are several factors particularly associated with recurrent
      falls, fall management and prevention strategies specifically targeting recurrent
      fallers require urgent evaluation in order to inform clinical practice.

PMID- 23533954
TI  - Playing piano can improve upper extremity function after stroke: case studies.
AB  - Music-supported therapy (MST) is an innovative approach that was shown to improve
      manual dexterity in acute stroke survivors. The feasibility of such intervention
      in chronic stroke survivors and its longer-term benefits, however, remain
      unknown. The objective of this pilot study was to estimate the short- and long
      term effects of a 3-week piano training program on upper extremity function in
      persons with chronic stroke. A multiple pre-post sequential design was used, with
      measurements taken at baseline (week0, week3), prior to (week6) and after the
      intervention (week9), and at 3-week follow-up (week12). Three persons with stroke
      participated in the 3-week piano training program that combined structured piano
      lessons to home practice program. The songs, played on an electronic keyboard,
      involved all 5 digits of the affected hand and were displayed using a user
      friendly MIDI program. After intervention, all the three participants showed
      improvements in their fine (nine hole peg test) and gross (box and block test)
      manual dexterity, as well as in the functional use of the upper extremity (Jebsen
      hand function test). Improvements were maintained at follow-up. These preliminary
      results support the feasibility of using an MST approach that combines structured
      lessons to home practice to improve upper extremity function in chronic stroke.

PMID- 23533955
TI  - Transcranial direct current stimulation in stroke rehabilitation: a review of
      recent advancements.
AB  - Transcranial direct current stimulation (tDCS) is a promising technique to treat
      a wide range of neurological conditions including stroke. The pathological
      processes following stroke may provide an exemplary system to investigate how
      tDCS promotes neuronal plasticity and functional recovery. Changes in synaptic
      function after stroke, such as reduced excitability, formation of aberrant
      connections, and deregulated plastic modifications, have been postulated to
      impede recovery from stroke. However, if tDCS could counteract these negative
      changes by influencing the system's neurophysiology, it would contribute to the
      formation of functionally meaningful connections and the maintenance of existing
      pathways. This paper is aimed at providing a review of underlying mechanisms of
      tDCS and its application to stroke. In addition, to maximize the effectiveness of
      tDCS in stroke rehabilitation, future research needs to determine the optimal
      stimulation protocols and parameters. We discuss how stimulation parameters could
      be optimized based on electrophysiological activity. In particular, we propose
      that cortical synchrony may represent a biomarker of tDCS efficacy to indicate
      communication between affected areas. Understanding the mechanisms by which tDCS
      affects the neural substrate after stroke and finding ways to optimize tDCS for
      each patient are key to effective rehabilitation approaches.

PMID- 23533956
TI  - Clinical trials in cardiac arrest and subarachnoid hemorrhage: lessons from the
      past and ideas for the future.
AB  - Introduction. Elevated intracranial pressure that occurs at the time of cerebral
      aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the
      brain injury cascade that occurs after cardiac arrest. Insights from clinical
      trials in cardiac arrest may provide direction for future early brain injury
      research after subarachnoid hemorrhage (SAH). Methods. A search of PubMed from
      1980 to 2012 and clinicaltrials.gov was conducted to identify published and
      ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients.
      Only English, adult, human studies with primary or secondary mortality or
      neurological outcomes were included. Results. A total of 142 trials (82 SAH, 60
      cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority
      of both published and ongoing SAH trials focus on delayed secondary insults after
      SAH (70%), while 100% of cardiac arrest trials tested interventions within the
      first few hours of ictus. No SAH trials addressing treatment of early brain
      injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest
      trials showed outcome benefit, though there is no overlap mechanistically.
      Conclusions. Clinical trials in SAH assessing acute brain injury are warranted
      and successful interventions identified by the cardiac arrest literature may be
      reasonable targets of the study.

PMID- 23533957
TI  - MicroRNAs in Cerebral Ischemia.
AB  - The risk of ischemic stroke increases substantially with age, making it the third
      leading cause of death and the leading cause of long-term disability in the
      world. Numerous studies demonstrated that genes, RNAs, and proteins are involved
      in the occurrence and development of stroke. Current studies found that microRNAs
      (miRNAs or miRs) are also closely related to the pathological process of stroke.
      miRNAs are a group of short, noncoding RNA molecules playing important role in
      posttranscriptional regulation of gene expression and they have emerged as
      regulators of ischemic preconditioning and ischemic postconditioning. Here we
      give an overview of the expression and function of miRNAs in the brain, miRNAs as
      biomarkers during cerebral ischemia, and clinical applications and limitations of
      miRNAs. Future prospects of miRNAs are also discussed.

PMID- 23533959
TI  - Gait impairment in a rat model of focal cerebral ischemia.
AB  - The availability of proper tests for gait evaluation following cerebral ischemia
      in rats has been limited. The automated, quantitative CatWalk system, which was
      initially designed to measure gait in models of spinal cord injury, neuropathic
      pain, and peripheral nerve injury, is said to be a useful tool for the study of
      motor impairment in stroke animals. Here we report our experiences of using
      CatWalk XT with rats subjected to transient middle cerebral artery occlusion
      (MCAO), during their six-week followup. Large corticostriatal infarct was
      confirmed by MRI in all MCAO rats, which was associated with severe sensorimotor
      impairment. In contrast, the gait impairment was at most mild, which is
      consistent with seemingly normal locomotion of MCAO rats. Many of the gait
      parameters were affected by body weight, walking speed, and motivation despite
      the use of a goal box. In addition, MCAO rats showed bilateral compensation,
      which was developed to stabilize proper locomotion. All of these interferences
      may confound the data interpretation. Taken together, the translational
      applicability of CatWalk XT in evaluating motor impairment and treatment efficacy
      remains to be limited at least in rats with severe corticostriatal infarct and
      loss of body weight.

PMID- 23533958
TI  - Early brain injury: a common mechanism in subarachnoid hemorrhage and global
      cerebral ischemia.
AB  - Early brain injury (EBI) has become an area of extreme interest in the recent
      years and seems to be a common denominator in the pathophysiology of global
      transient ischemia and subarachnoid hemorrhage (SAH). In this paper, we highlight
      the importance of cerebral hypoperfusion and other mechanisms that occur in
      tandem in both pathologies and underline their possible roles in triggering brain
      injury after hemorrhagic or ischemic strokes.

PMID- 23533960
TI  - Frontal lobe atrophy in depression after stroke.
AB  - Background. Frontal lobe atrophy (FLA) is associated with late life depression.
      However, the role that FLA plays in the development of depression after stroke
      (DAS) remains unknown. This study thus examined the association between FLA and
      DAS. Methods. A convenience sample of 705 Chinese patients with acute ischemic
      stroke admitted to the acute stroke unit of a university-affiliated regional
      hospital in Hong Kong participated in the study. A psychiatrist administered the
      Structural Clinical Interview for DSM-IV to all patients and made a diagnosis of
      DAS three months after the index stroke. Results. Eighty-five (12.1%) patients
      were diagnosed with DAS. In univariate analysis, the DAS patients were more
      likely to have severe FLA (14.1% versus 5.6%). Severe FLA remained an independent
      predictor of DAS in multivariate analysis, with an odds ratio of 2.6 (95%
      confidence intervals = 1.2-5.9). Conclusions. The results suggest that FLA may
      play a role in the pathogenesis of DAS, which supports the hypothesis that
      cumulative vascular burden may be important in predicting DAS. Further
      investigations are needed to clarify the impact of FLA on the clinical
      presentation, treatment response, and outcome of DAS in stroke survivors.

PMID- 23533961
TI  - Long-term use of a static hand-wrist orthosis in chronic stroke patients: a pilot
      study.
AB  - Background. Long-term splinting, using static orthoses to prevent contractures,
      is widely accepted in stroke patients with paresis of the upper limb. A number of
      stroke patients complain about increased pain and spasticity, which leads to the
      nonuse of the orthosis and a risk of developing a clenched fist. Objectives.
      Evaluating long-term use of static hand-wrist orthoses and experienced comfort in
      chronic stroke patients. Methods. Eleven stroke patients who were advised to use
      a static orthosis for at least one year ago were included. Semistructured
      telephone interviews were conducted to explore the long-term use and experienced
      comfort with the orthosis. Data were analyzed using descriptive statistics.
      Results. After at least one year, seven patients still wore the orthosis for the
      prescribed hours per day. Two patients were unable to wear the orthosis 8 hours
      per day, due to poor comfort. Two patients stopped using the orthosis because of
      an increase in spasticity or pain. Conclusions. These pilot data suggest that a
      number of stroke patients cannot tolerate a static orthosis over a long-term
      period because of discomfort. Without appropriate treatment opportunities, these
      patients will remain at risk of developing a clenched fist and will experience
      problems with daily activities and hygiene maintenance.

PMID- 23533962
TI  - Hypoxic-ischemic neonatal encephalopathy: animal experiments for neuroprotective
      therapies.
AB  - Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an
      important problem in modern perinatal medicine. In this paper, we would like to
      share some of the results of our recent studies on neuroprotective therapies in
      animal experiments, as well as some literature reviews. From the basic animal
      studies, we have now obtained some possible candidates for therapeutic measures
      against hypoxic-ischemic neonatal encephalopathy. For example, they are
      hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and
      growth factors, steroid, calcium channel blocker, vagal stimulation, some anti
      apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with
      stem cells, modulators of K(+)-ATP channels, and so on. Whether combination of
      these therapies may be more beneficial than any single therapy needs to be
      clarified. Hypoxia-ischemia is a complicated condition, in which the cause,
      severity, and time-course are different in each case. Likewise, each fetus has
      its own inherent potentials such as adaptation, preconditioning-tolerance, and
      intolerance. Therefore, further extensive studies are required to establish an
      individualized strategy for neuroprotection against perinatal hypoxic-ischemic
      insult.

PMID- 23533963
TI  - Stroke care in young patients.
AB  - The aims of this study were (i) to evaluate the clinical features of a
      consecutive series of young patients with ischemic stroke and (ii) to assess the
      changes in the clinical management of these patients over the study period. All
      consecutive cases of young adults aged 16 to 44 years, with ischemic stroke, that
      were admitted between 2000 and 2005 in 10 Italian hospitals were included. We
      retrospectively identified 324 patients. One or more vascular risk factors were
      present in 71.5% of the patients. With respect to the diagnostic process, an
      increase in the frequency of cerebral noninvasive angiographic studies and a
      decrease in the use of digital subtraction angiography were observed (P < 0.001
      and P = 0.03, resp.). Undetermined causes decreased over 5-year period of study
      (P < 0.001). The diagnosis of cardioembolism increased. Thrombolysis was
      performed for 7.7% of the patients. PFO closure (8%) was the most frequently
      employed surgical procedure. In conclusion, the clinical care that is given to
      young patients with ischemic stroke changed over the study period. In particular,
      we detected an evolution in the diagnostic process and a reduction in the number
      of undetermined cases.

PMID- 23533964
TI  - Depression after stroke and risk of mortality: a systematic review and meta
      analysis.
AB  - Background. Depression after stroke may have great burden on the likelihood of
      functional recovery and long-term outcomes. Objective. To estimate the
      association between depression after stroke and subsequent mortality. Methods. A
      systematic search of articles using PubMed and Web of Science databases was
      performed. Odds ratios (ORs) and hazard ratios (HRs) were used as association
      measures for pooled analyses, based on random-effects models. Results. Thirteen
      studies, involving 59,598 subjects suffering from stroke (6,052 with and 53,546
      without depression), had data suitable for meta-analysis. The pooled OR for
      mortality at followup in people suffering from depression after stroke was 1.22
      (1.02-1.47). Subgroups analyses highlighted that only studies with medium-term
      followup (2-5 years) showed a statistically significant association between
      depression and risk of death. Four studies had data suitable for further analysis
      of pooled HR. The meta-analysis revealed a HR for mortality of 1.52 (1.02-2.26)
      among people with depression after stroke. Conclusions. Despite some limitations,
      this paper confirms the potential role of depression on post stroke mortality.
      The relationship between depression and mortality after stroke seems to be
      related to the followup duration. Further research is needed to clarify the
      nature of the association between depression after stroke and mortality.

PMID- 23533965
TI  - Epidemiological study of animal leptospirosis in new caledonia.
AB  - Leptospirosis is an important zoonotic disease in the world and a real public
      health concern for many years in New Caledonia. A cross-sectional survey was
      carried out on domestic and wild animals from New Caledonia in April 2009. Blood
      samples were collected from 30 cattle, 29 deers, (Cervus timorensis russa), 25
      horses, 51 dogs, and 8 cats and were tested for 23 serovars of pathogenic
      Leptospira species by the microscopic agglutination test. From the total number
      of 143 samples, 84 (58.7%) were found to be positive towards one or several
      serovars of pathogenic leptospires. According to the species, the positive sera
      were obtained from 43% of 30 cattle, 72% of 29 Rusa deer, 80% of 25 horses, and
      43% of 51 dogs, and fromall of the 8 cats tested. This study shows the broad
      dispersion and the high prevalence of the different serogroups of pathogenic
      Leptospira species tested, particularly among deer and horses. The disease is
      endemic in domestic animals and concerns all the species.

PMID- 23533966
TI  - Simultaneous determination of hormonal residues in treated waters using ultrahigh
      performance liquid chromatography-tandem mass spectrometry.
AB  - In the last years, hormone consumption has increased exponentially. Because of
      that, hormone compounds are considered emerging pollutants since several studies
      have determinted their presence in water influents and effluents of wastewater
      treatment plants (WWTPs). In this study, a quantitative method for the
      simultaneous determination of oestrogens (estrone, 17 beta -estradiol, estriol,
      17 alpha -ethinylestradiol, and diethylstilbestrol), androgens (testosterone),
      and progestogens (norgestrel and megestrol acetate) has been developed to
      determine these compounds in wastewater samples. Due to the very low
      concentrations of target compounds in the environment, a solid phase extraction
      procedure has been optimized and developed to extract and preconcentrate the
      analytes. Determination and quantification were performed by ultrahigh
      performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The
      method developed presents satisfactory limits of detection (between 0.15 and 9.35
      ng.L(-1)), good recoveries (between 73 and 90% for the most of compounds), and
      low relative standard deviations (under 8.4%). Samples from influents and
      effluents of two wastewater treatment plants of Gran Canaria (Spain) were
      analyzed using the proposed method, finding several hormones with concentrations
      ranged from 5 to 300 ng.L(-1).

PMID- 23533969
TI  - Life in science: Hans-W. Ackermann.

PMID- 23533967
TI  - Mysterious meningioma: Surviving the odds.

PMID- 23533970
TI  - Ethics at crossroads: Global guidelines vs. local laws.

PMID- 23533971
TI  - Ethics in clinical research in India: A survey of clinical research
      professionals' perceptions.

PMID- 23533972
TI  - Ethical issues in clinical research.

PMID- 23533973
TI  - Ethics committees: Aspirations and responsibilities.

PMID- 23533974
TI  - Ethics committee member: Reviewing the 'Ethics' in clinical research.

PMID- 23533975
TI  - Informed consent: Past and present.

PMID- 23533976
TI  - Informed consent in clinical research: Revisiting few concepts and areas.

PMID- 23533978
TI  - Investigators viewpoint on ethics, methods, and informed consent in clinical
      trials.

PMID- 23533977
TI  - Championing ethics: industry viewpoint.

PMID- 23533979
TI  - Conflict of interest and its importance.

PMID- 23533980
TI  - What I wish every doctor knew: A patient perspective.

PMID- 23533981
TI  - Enough said, it's time to act.

PMID- 23533982
TI  - Placebo in clinical trials.

PMID- 23533983
TI  - Vulnerable population and methods for their safeguard.

PMID- 23533984
TI  - Post-trial access.

PMID- 23533985
TI  - Compensation for research related injury.

PMID- 23533986
TI  - Compensation in clinical research: The debate continues.

PMID- 23533987
TI  - Research ethics in real world studies.

PMID- 23533988
TI  - Current topics in research ethics in vaccine studies.

PMID- 23533989
TI  - Acquired immune deficiency syndrome vaccine trials: Managing ethical issues
      before, during and after the trials.

PMID- 23533991
TI  - Ethics of genomic research.

PMID- 23533990
TI  - Pediatric clinical trials.

PMID- 23533992
TI  - Stem cell research: The India perspective.

PMID- 23533993
TI  - Endnote: Vision of research ethics.

PMID- 23533995
TI  - Sex-associated expression of co-stimulatory molecules CD80, CD86, and accessory
      molecules, PDL-1, PDL-2 and MHC-II, in F480+ macrophages during murine
      cysticercosis.
AB  - Macrophages are critically involved in the interaction between T. crassiceps and
      the murine host immune system. Also, a strong gender-associated susceptibility to
      murine cysticercosis has been reported. Here, we examined the sex-associated
      expression of molecules MHC-II, CD80, CD86, PD-L1, and PD-L2 on peritoneal
      F4/80(hi) macrophages of BALB/c mice infected with Taenia crassiceps. Peritoneal
      macrophages from both sexes of mice were exposed to T. crassiceps total extract
      (TcEx). BALB/c Females mice recruit higher number of macrophages to the
      peritoneum. Macrophages from infected animals show increased expression of PDL2
      and CD80 that was dependent from the sex of the host. These findings suggest that
      macrophage recruitment at early time points during T. crassiceps infection is a
      possible mechanism that underlies the differential sex-associated susceptibility
      displayed by the mouse gender.

PMID- 23533996
TI  - Simultaneous quantification of flavonol glycosides, terpene lactones, biflavones,
      proanthocyanidins, and ginkgolic acids in Ginkgo biloba leaves from fruit
      cultivars by ultrahigh-performance liquid chromatography coupled with triple
      quadrupole mass spectrometry.
AB  - On the basis of liquid chromatography coupled with triple quadrupole mass
      spectrometry working in multiple reaction monitoring mode, an analytical method
      has been established to simultaneously determine flavonol glycosides, terpene
      lactones, biflavones, proanthocyanidins, and ginkgolic acids in Ginkgo biloba
      leaves. Chromatographic separation was carried out on an Acquity BEH C18 column
      (100 mm * 2.1 mm, 1.7  MU m) with gradient elution of acetonitrile and 0.10%
      formic acid (v/v) at a flow rate of 0.4 mL/min, and column temperature 30 degrees
      C. The developed method was validated in terms of linearity, accuracy, precision,
      stability, and sensitivity. The optimized method was successfully applied to
      analyze twenty-two G. biloba leaf samples of fruit cultivars collected from
      different places in China. Furthermore, hierarchical clustering analysis (HCA)
      was performed to evaluate and classify the samples according to the contents of
      the twenty-four chemical constituents. All of the results demonstrated that the
      developed method was useful for the overall evaluation of the quality of G.
      biloba leaves, and this study was also helpful for the comprehensive utilization
      and development of G. biloba resources.

PMID- 23533994
TI  - The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for
      tumor-associated macrophages.
AB  - Hepatocellular carcinoma (HCC) is one of the most common and aggressive human
      cancers worldwide. HCC is an example of inflammation-related cancer and
      represents a paradigm of the relation occurring between tumor microenvironment
      and tumor development. Tumor-associated macrophages (TAMs) are a major component
      of leukocyte infiltrate of tumors and play a pivotal role in tumor progression of
      inflammation-related cancer, including HCC. Several studies indicate that, in the
      tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote
      angiogenesis, metastasis, and suppression of adaptive immunity through the
      expression of cytokines, chemokines, growth factors, and matrix metalloproteases.
      Indeed, an established M2 macrophage population has been associated with poor
      prognosis in HCC. The molecular links that connect cancer cells and TAMs are not
      completely known, but recent studies have demonstrated that NF-kappaB, STAT-3,
      and HIF-1 signaling pathways play key roles in this crosstalk. In this paper, we
      discuss the current knowledge about the role of TAMs in HCC development,
      highlighting the role of TAM-derived cytokines, chemokines, and growth factors in
      the initiation and progression of liver cancer and outlining the signaling
      pathways involved in the interplay between cancer cells and TAMs.

PMID- 23533997
TI  - Alantolactone induces apoptosis in HepG2 cells through GSH depletion, inhibition
      of STAT3 activation, and mitochondrial dysfunction.
AB  - Signal transducer and activator of transcription 3 (STAT3) constitutively
      expresses in human liver cancer cells and has been implicated in apoptosis
      resistance and tumorigenesis. Alantolactone, a sesquiterpene lactone, has been
      shown to possess anticancer activities in various cancer cell lines. In our
      previous report, we showed that alantolactone induced apoptosis in U87
      glioblastoma cells via GSH depletion and ROS generation. However, the molecular
      mechanism of GSH depletion remained unexplored. The present study was conducted
      to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2
      cells by focusing on the molecular mechanism of GSH depletion and its effect on
      STAT3 activation. We found that alantolactone induced apoptosis in HepG2 cells in
      a dose-dependent manner. This alantolactone-induced apoptosis was found to be
      associated with GSH depletion, inhibition of STAT3 activation, ROS generation,
      mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio
      and caspase-3 activation. This alantolactone-induced apoptosis and GSH depletion
      were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L
      cysteine (NAC). The data demonstrate clearly that intracellular GSH plays a
      central role in alantolactone-induced apoptosis in HepG2 cells. Thus,
      alantolactone may become a lead chemotherapeutic candidate for the treatment of
      liver cancer.

PMID- 23533998
TI  - Size-dependent photodynamic activity of gold nanoparticles conjugate of water
      soluble purpurin-18-N-methyl-d-glucamine.
AB  - Gold nanoparticles (GNPs) conjugates of water soluble ionic photosensitizer (PS),
      purpurin-18-N-methyl-D-glucamine (Pu-18-NMGA), were synthesized using various
      molar ratios between HAuCl4 and Pu-18-NMGA without adding any particular reducing
      agents and surfactants. The PS-GNPs conjugates showed long wavelength absorption
      of range 702-762 nm, and their different shapes and diameters depend on the molar
      ratios used in the synthesis. In vitro anticancer efficacy of the PS-GNPs
      conjugates was investigated by MTT assay against A549 cells, resulting in higher
      photodynamic activity than that of the free Pu-18-NMGA. Among the PS-GNPs
      conjugates, the GNPs conjugate from the molar ratio of 1 : 2 (Au(III): Pu-18
      NMGA) exhibits the highest photodynamic activity corresponding to bigger size
      (~60 nm) of the GNPs conjugate which could efficiently transport the PS into the
      cells than that of smaller size of the GNPs conjugate.

PMID- 23534000
TI  - Contraction stresses in direct and indirect composite restorations compared by
      crack analysis.
AB  - PURPOSE: To compare contraction stresses in direct and indirect composite
      restorations using crack analysis. MATERIALS AND METHODS: Glass disks with a
      central cylindrical hole were prepared. Initial cracks were made in the glass
      using a Vickers indenter at various distances from the edge of the hole. The
      indentation crack lengths were measured parallel to the tangent of the edge of
      the hole. Silanized holes were directly or indirectly filled with a resin
      composite. The composite was either self-curing and light curing or only self
      curing. Various thicknesses of composite cement were applied to the indirect
      restorations. The crack lengths were re-measured 15 and 30 min after they were
      filled. The contraction stresses were calculated from the crack lengths and
      fracture toughness of the glass. Elastic moduli of light-cured and self-cured
      composite samples were measured using a nanoindentation method 15 and 30 min
      after curing. RESULTS: The stress could not be calculated for the light-cured
      direct composite and light-cured indirect composite restorations with thicker
      cement, due to glass failure caused by the contraction stress. Glass failure did
      not occur in the indirect composite restoration with thinner cement or in the
      self-cured direct composite restoration. The stress in the glass was lower for
      greater distances or shorter times. Factors of indentation-hole distance and
      restorative procedure significantly affected the stress. The measuring time and
      the type of curing had significant influence on the elastic modulus. CONCLUSION:
      Light-cured indirect composite restorations with a cement thickness < 200 um
      generated less contraction stress than did light-cured direct composite
      restorations. The lowest contraction stress was developed in the self-cured
      direct composite restoration.

PMID- 23533999
TI  - Chronic stress induces structural alterations in splenic lymphoid tissue that are
      associated with changes in corticosterone levels in wistar-kyoto rats.
AB  - Major depressive disorder patients present chronic stress and decreased immunity.
      The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary
      adrenal axis is overactivated. To determine whether chronic stress induces
      changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male
      rats were subject to restraint stress (3 h daily), chemical stress
      (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus
      hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The
      serum corticosterone levels by RIA and spleens morphology were analyzed.
      Corticosterone levels as did the structure, size of the follicles and morphology
      of the parenchyma (increase in red pulp) in the spleen, varied depending on time
      and type of stressor. These changes indicate that chronic stress alters the
      immune response in the spleen in WKY rats by inducing morphological changes,
      explaining in part the impaired immunity that develops in organisms that are
      exposed to chronic stress.

PMID- 23534001
TI  - Effects of warm air drying on water sorption, solubility, and adhesive strength
      of simplified etch-and-rinse adhesives.
AB  - PURPOSE: To evaluate the effects of the temperature of air used for solvent
      evaporation on water sorption, solubility, and ultimate tensile strength (UTS) of
      simplified etch-and-rinse adhesives. MATERIALS AND METHODS: Four commercial
      simplified etch-and-rinse adhesives (Adper Single Bond 2 [SB]; Te Econom [TE]; XP
      Bond [XP] and Ambar [AM]) were selected. Disk-shaped specimens were prepared by
      dispensing the uncured resin into a mold (5.8 mm x 0.8 mm). Solvent evaporation
      was performed using a warm (60 degrees C) or cold (20 degrees C) air stream for
      40 s. After desiccation, the cured specimens were weighed and then stored in
      distilled water for evaluation of the water diffusion kinetics over a 28-day
      period. For the UTS measurement, hourglass-shaped specimens of adhesives were
      prepared and tested in tension. The data from each test were evaluated with two
      way ANOVA and Tukey's test at a confidence level of 95%. RESULTS: Water sorption
      and solubility varied significantly between materials, but no significant
      difference was observed between warm and cold conditions (p > 0.05). TE and AM
      showed the lowest water sorption and solubility (p < 0.05). For SB, TE, and XP,
      the use of a warm air stream resulted in higher ultimate tensile strength (p <
      0.05) in both experimental conditions. CONCLUSIONS: The water sorption and
      solubility of the materials seem to be more influenced by their composition than
      by the temperature used for solvent evaporation. For some adhesives, the use of a
      warm air stream can yield higher ultimate tensile strength.

PMID- 23534002
TI  - Effect of photoactivation mode on the hardness and bond strength of methacrylate-
      and Silorane monomer-based composites.
AB  - PURPOSE: To evaluate the Knoop hardness (KH) and the bond strength (BS) at the
      tooth/restoration interface of conventional methacrylate- (Filtek Supreme) and
      silorane-based (Filtek P90) composites photoactivated by different methods using
      an LED Freelight 2. MATERIALS AND METHODS: Bond strength was tested in a
      universal testing machine by the "push-out" test in restored cavities measuring 2
      * 1.5 * 2 mm with a C-factor of 2.2, prepared in 60 bovine teeth. To restore the
      cavities, the respective adhesive system of each composite was used (Single Bond
      2 and P90 system adhesives). The composites were photoactivated by 3 different
      methods: continuous light: 40 s at 1000 mW/cm2; soft-start: 10 s at 150 mW/cm2 +
      38 s at 1000 mW/cm2; pulse delay: 5 s at 150 mW/cm2, followed by a 3-min wait
      (without photoactivation) and 39 s at 1000 mW/cm2. Before the push-out test was
      performed, the KH was analyzed at the top and bottom of the restorations. Data
      were statistically anaylzed using ANOVA and Tukey's test. RESULTS: The
      photoactivation methods produced no differences in BS or KH in the same
      composite, while Filtek P90 (28.0 MPa) showed higher BS values than Filtek
      Supreme (22.3 MPa) and a lower KH. CONCLUSION: The composite Filtek P90 was
      capable of increasing bond strength, but presented lower Knoop hardness.

PMID- 23534003
TI  - Does operatory field isolation influence the performance of direct adhesive
      restorations?
AB  - PURPOSE: To evaluate the influence of different adhesive strategies (etch-and
      rinse and self-etching adhesives) and type of field isolation (absolute or
      relative) on the clinical performance of restorations of noncervical carious
      lesions (NCCLs). MATERIALS AND METHODS: One hundred forty NCCLs were selected
      from 38 patients, according to previously established inclusion/exclusion
      criteria, and assigned to one of four groups (n = 35): etch-and-rinse/rubber-dam
      (ERR), etch-and-rinse/cotton roll (ERC), self-etching/rubber-dam (SER) and self
      etching/cotton roll (SEC). The adhesive systems used were: Adper Single Bond 2
      (3M ESPE) and Adper SE Plus (3M ESPE), with restorations made using a composite
      resin (Z350, 3M ESPE). Using the USPHS modified criteria, 140 restorations were
      evaluated by two calibrated examiners at 5 different times: immediately after
      placement, at 7 days, and 2, 6, and 12 months. In order to evaluate the presence
      of gingival recession after the use of the #212 rubber-dam clamp, the clinical
      crowns of the teeth from groups ERR and SER were measured at six different
      periods (baseline, immediately, and at 7 days, 2, 6, and 12 months). Data were
      subjected to McNemar's, chi-square, and Student's t-tests. RESULTS: Both adhesive
      strategies reduced tooth sensitivity beyond the second period of evaluation (7
      days); tooth sensitivity disappeared after the third period of evaluation (2
      months). There were no statistically significant differences between the adhesive
      techniques or isolation techniques, except for a Bravo score for marginal
      discoloration in group SEC at 6 months, which was significantly different from
      the other groups. The rubber-dam isolation technique was more uncomfortable for
      the patient and resulted in short-term gingival recession. CONCLUSION: No
      significant differences were found between the types of isolation or adhesive
      strategy in this clinical evaluation, with the exception of 2 restorations in
      group SEC that showed marginal discoloration, possibly due to inadequate enamel
      etching by the self-etching adhesive. Class V restorations perform equally well
      placed with or without rubber-dam.

PMID- 23534004
TI  - Push-out bond strength of a newly introduced glass fiber root canal filling
      material.
AB  - PURPOSE: To compare the push-out bond strength of a new glass fiber root canal
      filling material to that of Resilon/ Epiphany, EndoREZ, and gutta-percha/AH Plus
      root canal filling materials. MATERIALS AND METHODS: Sixty roots were randomly
      divided into four groups (n = 15) according to the obturation material: group 1,
      Resilon/Epiphany (RE) (Pentron Clinical Technologies); group 2, gutta-percha/AH
      Plus (GP) (Dentsply DeTrey); group 3, EndoREZ obturation system (ER) (Ultradent);
      and group 4, glass fiber root canal filling (GF) (Stick Tech) and dual-curing
      resin sealer (MetaSeal, Parkell). Two-mm-thick horizontal sections from the
      coronal, middle, and apical thirds of each root were sliced for the push-out bond
      strength measurement. RESULTS: GF showed the significantly highest mean bond
      strength values at the coronal and middle thirds. At the apical third, GF showed
      significantly higher bond strength values than did RE and ER. However, there was
      no significant difference at the apical third between the GF and GP groups. The
      lowest bond strength values were recorded for ER. CONCLUSION: Glass fiber root
      canal filling material seems to provide promising bond strength to root canal
      dentin.

PMID- 23534005
TI  - Restoration of primary anterior teeth using intracanal polyethylene fibers and
      composite: an in vivo study.
AB  - PURPOSE: To evaluate the clinical performance of polyethylene fiber for anterior
      primary teeth restorations in children after 2.5 years, according to modified
      Ryge criteria. MATERIALS AND METHODS: Fifty-five maxillary incisors with
      extensive caries in 24 Iranian patients (mean age 4.2 years) were restored. All
      teeth were treated endodontically. First, 4-mm layer of paste at the entrance of
      canal was removed, and a thin base layer of polycarboxylate cement was placed at
      the bottom of the prepared canal. All tooth surfaces were etched, rinsed and
      dried, and the dentin adhesive Single Bond (3M ESPE, St Paul, MN, USA) was
      applied. The teeth received intracanal fiber-reinforced resin (Ribbond Triaxial,
      Seattle, WA, USA) fixed with a flowable composite and the crowns were
      reconstructed with microhybrid composite resin (Z250, 3M). All restorations were
      evaluated every 6 months for 30 months by 2 independent evaluators. Statistical
      analysis was done with McNemar's test. RESULTS: The surface textures for most of
      the restorations were judged as excellent. There was no evidence of significant
      changes in marginal integrity. Most restored incisors (81%) received an Alpha
      rating for retention. The baseline and recall retention scores differed
      significantly (p=0.002). CONCLUSION: Polyethylene fiber posts associated with
      extensive composite restoration showed excellent clinical performance after 2.5
      years in primary anterior teeth after pulp therapy.

PMID- 23534006
TI  - Shear bond strength to enamel and flexural strength of different fiber-reinforced
      composites.
AB  - PURPOSE: To assess the shear bond strength to unground human enamel (ESBS) and
      flexural strength (FS) of different reinforcing fibers used in combination with a
      flowable composite resin. MATERIALS AND METHODS: For ESBS testing, 90 human
      molars were selected and randomly divided into 9 groups (n = 10) according to the
      reinforcing fiber to be tested: 1. RTD Quartz Splint additionally impregnated at
      chairside with Quartz Splint Resin (RTD); 2. RTD Quartz Splint without additional
      impregnation; 3. Ribbond-THM (Ribbond) impregnated with OptiBond FL Adhesive; 4:
      Ribbond Triaxial (Ribbond) impregnated with OptiBond FL Adhesive; 5. Connect
      (Kerr) impregnated with OptiBond FL Adhesive; 6. Construct (Kerr) impregnated
      with Opti- Bond FL Adhesive; 7. everStick PERIO (Stick Tech); 8. everStick C&B
      (Stick Tech); 9. nonreinforced composite Premise flowable (Kerr). Cylinders of
      flowable composite reinforced with the fibers were bonded to the intact buccal
      surface of the teeth. After 24 h of storage, shear loading was performed until
      failure occurred. FS was assessed performing three-point bending test according
      to ISO Standard 4049/2000. ESBS and FS data were analyzed using one-way ANOVA,
      followed by Tukey's HSD test for post-hoc comparisons (p < 0.05). RESULTS: For
      each group, the ESBS and FS, respectively, in MPa were: 1. 17.07 +/- 4.52 and
      472.69 +/- 30.49; 2. 14.98 +/- 3.92 and 441.77 +/- 61.43; 3. 18.59 +/- 5.67 and
      186.89 +/- 43.89; 4. 16.74 +/- 6.27 and 314.41 +/- 148.52; 5. 14.38 +/- 4.14 and
      223.80 +/- 77.35; 6. 16.00 +/- 5.55 and 287.62 +/- 85.91; 7. 16.42 +/- 3.67 and
      285.35 +/- 39.68; 8. 23.24 +/- 5.81 and 370.46 +/- 29.26; 9. 12.58 +/- 4.76 and
      87.75 +/- 22.87. For most fibers, no significant difference in ESBS was found
      compared to the control group, except for everStick C&B, which yielded higher
      ESBS. Nonreinforced composite exhibited the lowest FS, while all fibers
      positively affected the FS. CONCLUSIONS: Fiber reinforcement of flowable
      composite does not affect its ESBS. The flexural strength of FRCs is
      significantly influenced by fiber composition and pattern.

PMID- 23534007
TI  - Aging affects the adhesive interface of posts luted with self-adhesive cements: a
      1-year study.
AB  - PURPOSE: To examine the bond strength and interfacial nanoleakage expression of
      fiber posts luted to intraradicular dentin with self-adhesive cements. Six-month
      and 1-year aging effects were examined. MATERIALS AND METHODS: Post space was
      created in endodontically treated human incisors. Each tooth was assigned to a
      self-adhesive cement/post combination: (1) Bifix SE Cement (Voco) with
      proprietary posts (Rebilda Post, Voco), (2) RelyX Unicem (3M ESPE) with
      proprietary posts (Rely X Fiber Post, 3M ESPE), (3) MaxCem (Kerr) with Rebilda
      Posts. Each specimen was cut into 1-mm-thick sections and either immediately
      stressed to failure with the push-out bond strength test or aged in artificial
      saliva for 6 months or 1 year before testing. Additional specimens were processed
      for quantitative interfacial nanoleakage analysis using ammoniacal silver
      nitrate. RESULTS: Immediate bond strength ranked in the following order: Bifix SE
      (7.8 +/- 2.9 MPa) = RelyX Unicem (8.4 +/- 2.7 MPa) > MaxCem (4.6 +/- 2.4 MPa) (p
      < 0.05). Aging significantly reduced the bond strength of all cements after 1
      year: Bifix SE (3.8 +/- 1.4 MPa) = RelyX Unicem (5.8 +/- 1.7 MPa) > MaxCem (1.3
      +/- 0.9 MPa; p<0.05). No immediate difference in interfacial nanoleakage
      expression was found. Nanoleakage increased after aging, and MaxCem showed the
      highest values. CONCLUSION: The push-out strength and interfacial nanoleakage
      expression of fiber posts luted with self-adhesive cements were dependent on
      luting material and type of post, and were significantly affected by storage
      time.

PMID- 23534008
TI  - Effects of different cavity designs on fracture load of fiber-reinforced adhesive
      fixed dental prostheses in the anterior region.
AB  - PURPOSE: To evaluate the fracture strength of inlay-retained, surface-retained,
      and cantilevered fiber-reinforced adhesively fixed dental prostheses (FRA-FDPs)
      in the anterior region. MATERIALS AND METHODS: Thirty-two sound human right
      central incisors and canines were divided into four groups. Test groups were as
      follows: group 1, both teeth had deep cavity preparation; group 2, both teeth had
      shallow cavity preparation; group 3, only the canine teeth had deep cavity
      preparation; group 4, no preparation was made on the abutment teeth. Lateral
      pontics were restored with FRA-FDPs. All restorations were subjected to fracture
      loading from the lateral pontic. The restorations were tested in a universal
      testing machine (LRX Material Testing Machine) with a crosshead speed of 1
      mm/min. One-way ANOVA was used for statistical analyses. Fracture modes were
      examined visually. RESULTS: The highest (667.3 +/- 90.4 N) and the lowest (409.3
      +/- 158.1 N) debonding values were found for groups 4 and 3, respectively.
      CONCLUSIONS: Different preparation designs (inlay-retained, surface-retained) had
      no significant effect on fracture strength of FRA-FDPs in the anterior region.
      However, a cantilever design exhibited significantly lower fracture strength.
      Delamination of the veneering composite was observed as the primary failure type
      after fracture tests.

PMID- 23534009
TI  - Starch tubing: an alternative method to build up microshear bond test specimens.
AB  - PURPOSE: To evaluate an alternative device using starch tubes to build up resin
      composite specimens for microshear bond tests. MATERIALS AND METHODS: Twenty
      human molars were selected and sectioned mesiodistally to obtain two sections.
      The teeth were randomly divided into 4 groups (n = 10) according to the adhesive
      system - a two-step etch-and-rinse adhesive (Adper Single Bond) and a two-step
      self-etching adhesive (Clearfil SE Bond) - and the type of tube, starch or
      polyethylene. The tubes were evaluated under a stereomicroscope at 25X
      magnification to observe the variation in internal diameter. The resin composite
      was bonded to flat enamel surfaces using one of the adhesive systems and tube
      types. After 24 h storage in distilled water, the microshear bond strength (uSBS)
      was determined and the fracture pattern was analyzed under a stereomicroscope
      (400X magnification). The microshear bond strength values were subjected to two
      way ANOVA. The chi-square test was used to compare pre-test failures and fracture
      patterns between the groups (p < 0.05). RESULTS: The type of tube, the adhesive
      system, and their interaction did not influence the bond strength values (p =
      0.062, p = 0.122, and p = 0.301, respectively). No significant differences were
      observed for pre-test failures or fracture patterns (p = 0.320 and p = 0.561,
      respectively). CONCLUSION: Using starch tubes is an alternative to build up
      composite resin specimens for microshear bond strength testing with the two
      tested adhesive systems.

PMID- 23534010
TI  - Shrinkage kinetics of a methacrylate- and a silorane-based resin composite:
      effect on marginal integrity.
AB  - PURPOSE: To evaluate the relation between the linear displacement (LD), shrinkage
      force (SF) and marginal adaptation of a methacrylate- and a silorane-based
      composite. MATERIALS AND METHODS: The LD and SF of 8 samples made of Filtek
      Supreme XT (methacrylate-based composite) and Filtek Silorane (silorane-based
      composite) were measured for 180 s from the start of polymerization. Large bulk
      filled Class I cavities were restored with both resin composites, and two C
      factors were simulated by applying the same adhesive system in different ways:
      the Silorane System Adhesive (SSA) was applied on enamel and dentin (C-factor
      3.5) or only on enamel margins (C-factor of 0.4). Percentages of continuous
      margins (%CM) were quantitatively assessed with SEM before and after
      simultaneously loading with 1.2 million mechanical occlusal cycles (49 N; 1.7 Hz)
      and 3000 thermal cycles (5 degrees C to 50 degrees C) under dentinal fluid
      simulation. RESULTS: Significantly lower scores of LD and SF were observed for
      Filtek Silorane (LD: 12.0 um +/- 1.3, SF: 13.7 N +/- 1.0) than for Filtek Supreme
      XT (LD: 25.0 um +/- 0.6, SF: 36.3 N +/- 2.9). Both variables, ie, composite type
      and C-factor, had a significant effect on marginal adaptation (p < 0.05). In the
      groups with high C-factor (SSA was applied on the entire cavity surface) percent
      of continuous margin (%CM) (mean +/- SD) before and after loading, respectively,
      was 24.4 +/- 16.6 and 2.1 +/- 2.4 for Filtek Supreme XT, and 58.8 +/- 9.9 and
      35.4 +/- 4.1 for Filtek Silorane. When adhesion was confined to enamel margins
      (lower C-factor), %CM before and after loading, respectively, increased to 76.1
      +/- 9.6 and 64.2 +/- 11.5 for Filtek Supreme XT, and 96.6 +/- 1.7 and 94.2 +/-
      2.1 for Filtek Silorane. CONCLUSIONS: The silorane-based composite exhibited
      significantly lower shrinkage forces and better marginal adaptation than did the
      methacrylate-based composite.

PMID- 23534011
TI  - Effect of hydrophilicity on the compatibility between a dual-curing resin cement
      and one-bottle simplified adhesives.
AB  - PURPOSE: To evaluate the effect of the hydrophilicity of adhesives on the
      compatibility between one-bottle simplified adhesives and a dual-curing resin
      cement. MATERIALS AND METHODS: Three experimental and two commercial adhesives
      (All-Bond Universal, OptiBond Allin- One) with the same or similar pH and various
      degrees of hydrophilicity were tested in this study. Extracted human dentin was
      treated with each adhesive and bonded with a dual-curing resin cement (Duolink),
      which was either light cured or chemically (self) cured (n = 10). Shear bond
      strength was tested using the Ultradent jig method, and failure modes were
      determined using a stereomicroscope. Water contact angle (as a measure of
      hydrophilicity/-phobicity) was measured on a fully cured adhesive (n = 10). The
      data were analyzed statistically by ANOVA and Tukey's test. The quantitative
      relationship between the hydrophilicity and bond strength differences was
      analyzed (confidence level 95%). RESULTS: Among the experimental adhesives,
      differences in bond strengths between light-curing and self-curing modes were
      larger for the more hydrophilic adhesives. For the commercial adhesives, Optibond
      All-in-One had a lower contact angle than All-bond Universal (p < 0.05). Bond
      strength (MPa) values for Optibond All-in-One and All-bond Universal were 29.6
      and 31.5, respectively (light cured), and 1.9 and 30.0, respectively (self
      cured). Adhesive failure was a predominant mode for all adhesives except for All
      Bond Universal. Regression analysis indicated a linear correlation between
      adhesives' hydrophilicity and bond strength differences (p < 0.05). CONCLUSION:
      The more hydrophilic adhesives were less compatible (larger bond strength
      differences between different curing modes) with this dual-curing resin cement.
      All-bond Universal is more hydrophobic than Optibond All-in-One and it is
      compatible with this self-/dual-curing resin cement.

PMID- 23534012
TI  - 3D assessment of void and gap formation in flowable resin composites using
      optical coherence tomography.
AB  - PURPOSE: To investigate the effect of composite type and cavity size on gap and
      void formation using optical coherence tomography (OCT). MATERIALS AND METHODS:
      Class I cavities of two depths (2 mm or 4 mm; 4 mm diameter) were prepared,
      treated with Tri-S Bond (Kuraray Medical), and bulk filled with either Surefil
      SDR Flow (SF; Dentsply) or Clearfil Majesty LV (MJ; Kuraray Medical) to form four
      groups. After 24 h, the specimens were 3D scanned using swept-source OCT (Santec)
      with 1310 nm laser at a 20 kHz sweep rate. In OCT tomograms, the bonding
      interface and the bulk of the restorations were evaluated. The percentage values
      of sealed interfaces (SP) and void volume (VP) for all groups were calculated and
      statistically analyzed using two- and one-way ANOVA and Tukey's post-hoc test.
      Selected specimens were cross sectioned and observed using a scanning electron
      microscope (SEM) and a confocal laser scanning microscope to confirm OCT
      findings. RESULTS: The following values were obtained for SP and VP,
      respectively: SF-2mm: 92% and 0.08%; SF-4mm: 66% and 0.13%; MJ-2mm: 86% and
      1.79%; MJ-4mm: 33% and 1.96%. Both composites showed a significant increase in
      gap formation at 4-mm cavity depth (p < 0.001). While SF showed a rather
      homogeneous bulk compared to MJ, cavity depth did not significantly affect the
      void volume fraction (p = 0.08). CONCLUSION: The flowable composite with SDR
      (stress-decreasing resin) technology performed better than the conventional
      composite; however, bulk filling a 4-mm-deep cavity will compromise the sealing
      of the bonding interface regardless of the type of composite. OCT is a unique
      method of characterizing materials and their behaviors nondestructively and
      precisely.

PMID- 23534013
TI  - Effect of resin cement type on the microtensile bond strength to lithium
      disilicate ceramic and dentin using different test assemblies.
AB  - PURPOSE: This study evaluated the microtensile bond strength (uTBS) of 3
      different resin cements to lithium-disilicate ceramic using two assemblies:
      ceramic-cement-ceramic (CCC) and ceramic-cement-dentin (CCD). MATERIALS AND
      METHODS: The bonding surfaces of lithium disilicate ceramic blocks (5 * 5 * 4 mm)
      (Nblock = 90) were etched with 4% hydrofluoric acid for 20 s and silanized. Flat
      dentin surfaces of human third molars were conditioned according to the
      respective manufacturer's specifications for three types of resin cements (ML:
      Multilink, Ivoclar-Vivadent; PF: Panavia F, Kuraray; SB: Super Bond C&B, Sun
      Medical). While one set of ceramic blocks (n = 30) was cemented to another equal
      set (CCC assembly), another set of ceramic blocks (n = 30) was cemented on flat
      dentin (CCD assembly). The bonded specimens were stored in distilled water at 37
      degrees C for 24 h, and then sectioned along the x- and y-axes to obtain
      nontrimmed beam specimens. The beam specimens were randomly divided into two
      conditions: dry condition (DC - immediate testing); and aging condition (AC -
      thermocycling 12,000 times + water storage for 150 days). The uTBS bond strength
      test was performed using a universal testing machine (1 mm/min). After debonding,
      the substrate and adherent surfaces were analyzed using a scanning electron
      microscope to categorize the failure types. The data were statistically evaluated
      using 2-way ANOVA and Tukey's test (5%). RESULTS: While the mean uTBS of CCC
      assemblies were significantly influenced by the cement type (p < 0.05) and aging
      (p < 0.05), CCD assemblies showed a significant effect of the cement (p < 0.05)
      but not the aging (p > 0.05). Without aging (DC), the mean uTBS (MPa) of SB
      (26.9) and PF (26.9) were significantly higher than ML (18.5) (p < 0.05). For CCC
      after aging (AC), SB (26.6) showed higher mean uTBS than those of PF (16.4) and
      ML (18.5) (p < 0.05). However, in CCD after AC, no significant difference was
      found between the groups (p > 0.05). In both CCC and CCD assemblies, pre-test
      failures were the least with SB cement. Regardless of the resin cement type
      employed and storage conditions, adhesive failures ranged between 35.3% and
      88.9%, cohesive failures in cement between 2.3% and 35.3%, and cohesive failures
      in ceramic between 3.3% and 6.8%. CONCLUSION: SB resin cement demonstrated the
      highest bond strength to a lithium disilicate ceramic in both tests assemblies
      with and without aging conditions.

PMID- 23534014
TI  - Reconsidering the double etching of enamel: do self-etching primers contaminate
      phosphoric acid-etched enamel?
AB  - PURPOSE: To evaluate the composite-to-enamel bond following double etching of the
      enamel using phosphoric acid and different self-etching (SE) bonding systems with
      and without the application of their respective acidic primers. MATERIALS AND
      METHODS: The enamel surfaces of 90 human molars were ground (600 grit) flat and
      randomly divided into nine groups (n = 10). Three two-step SE systems (AdheSE,
      ASE; Clearfil SE Bond, CSE; OptiBond Solo Plus SE, OSE) were tested, both with
      and without primer application on enamel pre-etched with phosphoric acid under
      dry bonding conditions. As the controls, the SE systems were applied according to
      their original directions without pre-etching. All the specimens were built up
      with a microhybrid composite resin (Arabesk Top). After water storage for 24 h at
      37 degrees C, the bonded specimens were sheared to failure in the Zwicki 1120.
      Etching and failure patterns were evaluated using a scanning electron microscope
      (SEM). Shear bond strength was analyzed with two-way ANOVA and Tukey's test.
      Failure modes were analyzed with Fisher's exact test. RESULTS: Without pre
      etching, CSE showed significantly higher bond strengths than ASE and OSE (p <
      0.05). Enamel etching prior to the application of the SE systems tended to result
      in higher bond strengths, but significantly increased the values only for ASE (p
      < 0.05). Contamination of the pre-etched enamel with the SE primer decreased the
      bond strength by values of 19% for ASE (p > 0.05), 36% for CSE (p < 0.05), and
      75% for OSE (p < 0.05). SEM analysis showed that omission of the priming step
      significantly increased the number of cohesive failures within the resin for OSE
      (p < 0.0001). CONCLUSION: Additional etching with phosphoric acid before the
      application of SE systems does not necessarily result in better enamel bonding,
      since unavoidable primer contamination of the pre-etched enamel was shown to
      significantly reduce the bond strength for two of the three systems tested.

PMID- 23534015
TI  - Comparison between different flow application techniques: SDR vs flowable
      composite.
AB  - PURPOSE: To evaluate the effect of layer thickness of flowable composites on the
      marginal adaptation of Class II fillings after thermomechanical loading (TML).
      MATERIALS AND METHODS: Sixty standardized Class II box cavities were prepared
      under simulation of intrapulpal pressure with gingival margins located 1 mm below
      the cementoenamel junction (CEJ) in dentin. The samples were evenly distributed
      into six groups (A to F). After adhesive (XPBond) application, box preparations
      were filled with a first increment of either a nanohybrid composite (A, D)
      Ceram.X mono, or with one of two flowable materials SDR (B, E) or x-Flow (C, F).
      The first increments were 1 (A,B,C) or 4 mm (D,E,F) thick. All cavities were
      finally filled incrementally with Ceram.X mono. Replicas were prepared before and
      after TML (1.2 x 106 cycles; 5/50 degrees C; maximum load 49 N). Replicas were
      evaluated for marginal adaptation (tooth/composite) using scanning electron
      microscopy (200X). The percentage of continuous margins was compared between and
      within groups before and after TML using ANOVA and Scheffe's post-hoc tests.
      RESULTS: For group F before TML, adaptation of cervical margins located in dentin
      was compromised compared to the other groups (p < 0.05). After TML, at the same
      location, group F showed significantly worse adaptation compared with groups A to
      C and E (p < 0.05), but no difference to group D was found. The marginal
      integrity of all interfaces before and after TML was significantly worse in group
      F compared with all other groups (p < 0.05). CONCLUSION: Different flow
      application techniques for Class II cavities have an influence on the marginal
      adaptation (before/after TML). Applying a 4-mm first increment, both Ceram.X mono
      and SDR showed no differences vs groups in which the first increment was 1 mm
      thick.

PMID- 23534016
TI  - Effects of sandblasting and laser irradiation on shear bond strength of low
      fusing porcelain to titanium.
AB  - PURPOSE: To investigate the bond strength of low-fusing porcelain to commercially
      pure titanium (Ti) that was laser irradiated with different levels of energy and
      sandblasted. MATERIALS AND METHODS: A total of 30 titanium rods (10 mm in length
      and 12 mm in diameter) were prepared. The rods were divided into three groups (n
      = 10) according to surface treatments: SB: sandblasted; L1: Nd:YAG laser
      irradiated at 100 mJ, 10 Hz, and 1 W; L2: Nd:YAG laser irradiated at 200 mJ, 10
      Hz, and 2 W. After surface treatment, low-fusing porcelain was applied onto the
      titanium specimens according to the manufacturer's instructions, and these
      specimens were stored in distilled water at 37 degrees C for 24 h. The shear bond
      strength test was performed at a crosshead speed of 1 mm/min. In addition,
      Kruskal-Wallis and Mann-Whitney U-tests were used to compare the bond strength
      results (alpha = 0.05). SEM and EDS analysis were also performed for one specimen
      of each group after the shear bond strength test to evaluate the nature of the
      fracture surface. RESULTS: Group L2 produced the highest shear bond strength
      among the groups. There was a statistically significant difference in shear bond
      strength between groups L1 and L2 (p < 0.001). Nevertheless, no significant
      difference was found between groups SB and L1. EDS analysis revealed that laser
      treatment reduced presence of oxygen on the surface of Ti. In contrast to the
      sandblasted specimens, laser-irradiated specimens showed predominantly adhesive
      failure. CONCLUSION: Laser treatment may be an alternative method to sandblasting
      for enhancing the bond strength of low-fusing porcelain to commercially pure
      titanium.

PMID- 23534017
TI  - Effect of two different types of fibers on the fracture resistance of
      endodontically treated molars restored with composite resin.
AB  - PURPOSE: To compare the in vitro fracture resistance of endodontically treated
      molars with mesio-occluso-distal (MOD) cavities restored with two different types
      of fibers. MATERIALS AND METHODS: Sixty extracted human mandibular first molars
      were selected for the study and randomly assigned to six groups (n = 10). Group 1
      served as the control. In groups 2 through 6, endodontic access and standard MOD
      cavities were prepared. Following root canal treatment, group 2 was left
      unrestored. In group 3, the teeth were restored with composite resin (Venus,
      Heraeus Kulzer). In group 4, flowable composite resin (Venus, Heraeus Kulzer) was
      used before restoring the teeth with composite resin. In group 5, leno-woven
      ultrahigh molecular weight polyethylene ribbon fiber (Ribbond) was inserted in
      the flowable resin in a buccal to lingual direction, and the teeth were then
      restored with composite resin. In group 6, translucent glass fiber (Vectris,
      Ivoclar) was adapted over the flowable resin in the bucco-lingual direction and
      restored with composite resin. The specimens were stored in 100% humidity at 37
      degrees C for 1 day. Compressive loading of the teeth was performed using a
      universal testing machine at a crosshead speed of 0.5 mm/min. The mean load
      necessary to fracture the samples was recorded in Newtons (N). Data were
      subjected to analysis of variance (ANOVA) and Duncan's post-hoc test, where
      significance was set at p < 0.001. RESULTS: The highest and the lowest mean
      fracture strengths were found in sound teeth (1598.8 N) and unrestored teeth
      (393.7 N), respectively. The mean load necessary to fracture the samples was
      958.6 N in the polyethylene ribbon group (group 5), 913.2 N in the glass-fiber
      group (group 6), 699.7 N in teeth restored with flowable resin and composite
      (group 4), and 729.3 N in group 3 with composite resin alone. Statistical
      analysis showed significantly higher fracture resistance of both the fiber groups
      compared to composite resin alone (p < 0.001). CONCLUSION: Both polyethylene
      ribbon and glass fiber under MOD composite restorations significantly increased
      fracture strength with no statistical difference between the two groups.
      Therefore, both polyethylene- and glassfiber- reinforced composites can be used
      for access cavity restorations in teeth with weakened cusps.

PMID- 23534018
TI  - Chlorhexidine application in adhesive procedures: a meta-regression analysis.
AB  - PURPOSE: To evaluate the association between chlorhexidine application and the
      bond strength of an adhesive system to dentin and to assess the association among
      eight other variables. MATERIALS AND METHODS: Laboratory studies evaluating the
      use of chlorhexidine on dentin that verified the immediate and longitudinal bond
      strength were included. The terms were selected according to the Medical Subject
      Headings (MeSH) for PubMed and adapted for the other databases accordingly.
      Systematic searches were conducted in 3 electronic databases in December 2010:
      PubMed, EMBASE, and LILACS. Languages were limited to English, Spanish, and
      Portuguese. RESULTS: All longitudinal bond strength studies were analyzed in
      accordance with the inclusion/exclusion criteria, totaling 16 articles. A meta
      regression analysis was performed with articles containing complete mean bond
      strength data (n = 14 articles). CONCLUSION: Our results showed that the
      association between the concentration of chlorhexidine and the bond strength is,
      apparently, not linear. Therefore, future large-scale studies should be developed
      to investigate the association between the chlorhexidine concentration and hybrid
      layer preservation.

PMID- 23534019
TI  - Effect of water storage on bond strength of self-adhesive resin cements to
      zirconium oxide ceramic.
AB  - PURPOSE: To evaluate the microshear bond strength of resin cements to yttrium
      stabilized tetragonal zirconium oxide surfaces after water storage for 24 h or 1
      year. MATERIALS AND METHODS: Four self-adhesive (BisCem, G-Cem, RelyX Unicem,
      SeT) and one conventional resin cement (RelyX ARC) were tested. The materials
      were mixed and inserted in tubes (0.75 mm diameter * 1 mm height) that were
      placed over the zirconium oxide surface. Specimens were tested after 24-h or 1
      year water storage. Microshear testing was performed using a universal testing
      machine. Shear bond strength results were analyzed using two-way ANOVA and
      Tukey's test (5%). RESULTS: After 24-h water storage, no difference was found
      between G-Cem and RelyX Unicem resin cements; however, their bond strength means
      to zirconium oxide were statistically higher than RelyX ARC. The bond strength
      values of all resin cements dropped significantly after 1 year of water storage.
      G-Cem presented the highest values among cements after long-term water exposure.
      CONCLUSIONS: One-year water storage decreased the microshear bond strengths to
      zirconium oxide for all resin cements tested.

PMID- 23534020
TI  - Influence of MDPB-containing primer on Streptococcus mutans biofilm formation in
      simulated Class I restorations.
AB  - PURPOSE: To evaluate the activity of a methacryloyloxydodecylpyridinium bromide
      (MDPB)-containing self-etching primer (Clearfil Protect Bond) against
      Streptococcus mutans and its ability to reduce biofilm formation on standardized
      experimental Class I restorations in vitro. MATERIALS AND METHODS: Forty
      experimental Class I round restorations were prepared on enamel-dentin slabs
      using different adhesive strategies: group 1 = MDPB-containing adhesive system
      (Clearfil Protect Bond); group 2 = MDPB-free self-etching adhesive system
      (Clearfil SE Bond); group 3: MDPB-containing self-etching primer in combination
      with a fluoride-free bonding agent; group 4: MDPB-free self-etching primer in
      combination with a fluoride-containing bonding agent; group 5: a three-step etch
      and-rinse adhesive system (Adper Scotchbond Multi Purpose). A Streptococcus
      mutans biofilm was grown for 48 h on the restoration surfaces and subsequently
      evaluated using scanning electron microscopy on three different areas: enamel,
      composite, and interface surfaces. Statistical analysis was performed by multiple
      ANOVA after data transformation. RESULTS: Specimens in groups 2, 4 and 5 showed
      greater biofilm formation than those in groups 1 and 3 (p < 0.001) on all
      investigated substrates (enamel, composite, and interface areas). CONCLUSIONS:
      Specimens prepared with an MDPB-containing primer exhibited significant decreases
      in biofilm formation on Class I restorations in vitro. Further in vitro and in
      vivo studies are required to clarify the role of quaternary ammonium compounds in
      reducing bacterial biofilm formation on restoration surfaces.

PMID- 23534021
TI  - Immediate shear bond strengths of a composite, a compomer and a glass ionomer to
      a ceramic substrate.
AB  - PURPOSE: To determine the best-performing combination of three core buildup
      materials and three bonding materials based on their bond strength to ceramic
      blocks in vitro. MATERIALS AND METHODS: The materials used for core buildup were
      a composite (Tetric EvoCeram), a compomer (Compoglass F), and a glass-ionomer
      cement (Ketac Fil Plus), and for bonding, a three-step etch-and-rinse adhesive
      (Syntac), a two-step etch-and-rinse adhesive (ExciTE), and a single-step system
      (RelyX Unicem). Bond strength to ceramic blocks was determined by shear bond
      strength testing. Fracture behavior was evaluated by scanning electron
      microscopy. RESULTS: The highest adhesive values between buildup and ceramic were
      obtained using the materials Compoglass F and Syntac, followed by Compoglass F
      and ExciTE. Among the two other core buildups, Tetric EvoCeram performed better
      than Ketac Fil Plus, which was independent of the bonding materials. Adhesive
      fractures were characteristically observed with Syntac and ExciTE, and cohesive
      fractures were characteristically observed with RelyX Unicem. CONCLUSION: These
      data show that compomers bonded with a multistep adhesive system achieved
      statistically significantly higher shear bond strength than composites and glass
      ionomer cements. Within the limitations inherent to this in vitro study, the use
      of compomers for core buildup can be recommended.

PMID- 23534022
TI  - Bonding of simplified adhesive systems to caries-affected dentin of primary
      teeth.
AB  - PURPOSE: To evaluate the bonding of simplified adhesive systems to sound and
      caries-affected dentin of primary teeth with microtensile (uTBS) and nanoleakage
      (NL) tests. MATERIALS AND METHODS: Occlusal cavities were prepared in 36 sound
      second primary molars. Half of the specimens were submitted to pH cycling to
      simulate caries-affected dentin. Teeth were randomly restored with one of three
      materials: the etch-and-rinse adhesive system Adper Single Bond 2 (SB), the two
      step self-etching adhesive system Adper SE Plus (SE), and the one-step self
      etching adhesive system Adper Easy One (EASY). After storage for 24 h, specimens
      with cross-sectional areas of 0.8 mm2 were prepared for microtensile testing (1
      mm/min). One stick from each tooth was immersed in silver nitrate solution (24 h)
      and allowed to develop for 8 h in order to score the nano leakage with SEM. The
      fracture pattern was evaluated using a stereomicroscope (400X). The uTBS means
      were analyzed by two-way ANOVA and Tukey's post-hoc test. For NL, the Kruskal-
      Wallis and Mann-Whitney tests were used (alpha < 0.05). RESULTS: SB (35.5 +/-
      3.5) showed the highest uTBS value to sound dentin, followed by EASY (26.3 +/-
      1.9) and SE (18.2 +/- 6.5) (p < 0.05). No difference among materials was observed
      for caries-affected dentin (SB: 17.8 +/- 4.2; SE: 13.9 +/- 3.2; EASY: 14.4 +/-
      4.2, p > 0.05). For all groups, adhesive/mixed fracture prevailed. Caries
      affected dentin promoted silver nitrate uptake into the adhesive interface;
      however, with SE, the nano leakage was more pronounced than in the other adhesive
      systems, even in sound dentin. CONCLUSION: Caries-affected dentin negatively
      influences the bond strength and nano leakage of the two-step etch-and-rinse and
      one-step self-etching adhesive systems tested in primary teeth.

PMID- 23534023
TI  - Effects of silane application on luting fiber posts using self-adhesive resin
      cement.
AB  - PURPOSE: To evaluate the effects of different glass-fiber post surface treatments
      on the bond strength to root dentin. MATERIALS AND METHODS: Fifty bovine incisors
      were used in this study. After removing the crowns, the teeth were endodontically
      treated. The roots were randomly divided into five groups according to post
      surface treatment. The groups were as follows: CO (Control) - no treatment; G1 -
      RelyX Ceramic Primer (silane) only; G2 - silane and Solobond M; G3 - silane and
      Scotchbond Adhesive; G4 - silane and Excite. For post cementation, RelyX Unicem
      was used according to the manufacturer's recommendation and the roots were stored
      in a light-proof container with 100% relative humidity for 24 h. The specimens
      were transversally sectioned. Subsequently, the cervical, middle, and apical
      regions of the root were positioned in a push-out device and tested at 0.5 mm/min
      using a universal testing machine (Instron). The data were statistically analyzed
      with two-way ANOVA and Tukey's post-hoc test. The fractured specimens were then
      observed under a stereoscopic loupe at 60X magnification. RESULTS: No significant
      difference in bond strength was found among the groups that received a silane or
      silane plus an adhesive system (p > 0.05). However, the CO (no silane) showed the
      lowest bond strength. Regarding G1, G2, G3, and G4, the cervical region of the
      root canal attained better bond strengths than did the middle or apical regions.
      The most frequent failure mode occurred at the cement/dentin interface.
      CONCLUSION: Silane application may be necessary to improve the adhesion of fiber
      posts luted with the self-adhesive resin cement evaluated here. The application
      of an adhesive layer between the fiber post and resin cement did not have any
      influence on the bond strength when the silane coupling was previously used.

PMID- 23534025
TI  - Randomized clinical trial of indirect resin composite and ceramic veneers: up to
      3-year follow-up.
AB  - PURPOSE: This randomized controlled split-mouth clinical trial evaluated the
      short-term survival rate of indirect resin composite and ceramic laminate
      veneers. MATERIALS AND METHODS: A total of 10 patients (mean age: 48.6 years)
      received 46 indirect resin composite (Estenia; n = 23) and ceramic laminate
      veneers (IPS Empress Esthetic; n = 23) on the maxillary anterior teeth. Veneer
      preparations with incisal overlap were performed and existing resin composite
      restorations of good quality were not removed but conditioned using silica
      coating (CoJet) and silanization (ESPE-Sil). Enamel and dentin were etched and
      rinsed; adhesive resin (ExciTE) was then applied. After cementation (Variolink
      Veneer), restorations were evaluated at baseline and thereafter every 6 months
      for up to 3 years using modified USPHS criteria. RESULTS: Seventeen laminate
      veneers were bonded onto intact teeth and 29 on teeth having existing resin
      composite restorations. In total, 3 failures were observed in the form of
      debonding (n = 1) and fracture (n = 2) in the group of resin composite laminate
      veneers. No significant difference was observed between the survival rates of
      composite and ceramic laminate veneers (Estenia: 87%, IPS Empress Esthetic: 100%;
      p > 0.05). The overall survival rate was 93.5% (Kaplan-Meier). Of the 43 laminate
      veneers, minor voids and defects were observed in 6 of the composite and 3 of the
      ceramic veneers. Slight staining at the margins (n = 3) and slightly rough
      surfaces were more frequently observed for the resin composite laminate veneers
      (n = 18) up to the final recall. CONCLUSION: Early findings of this clinical
      trial on two veneer materials showed statistically similar survival rates.
      Surface quality changes were more frequent in the composite veneer material.

PMID- 23534024
TI  - Silica-based nano-coating on zirconia surfaces using reactive magnetron
      sputtering: effect on chemical adhesion of resin cements.
AB  - PURPOSE: To compare the effect of silica (Si)-based nano-coating deposited by
      reactive magnetron sputtering (RMP) with that of conventional surface
      conditioning using metal/zirconia primer alone or after air-particle abrasion on
      the adhesion of resin cements to zirconia ceramic. MATERIALS AND METHODS: Two
      hundred forty zirconia ceramic blocks (Cercon) were sintered, finished with 1200-
      grit SiC paper under water cooling, and cleaned ultrasonically in distilled water
      for 10 min. The blocks (4.5 mm x 3.5 mm x 4.5 mm) were randomly divided into 24
      groups (n = 10) according to 3 testing parameters: a) resin cements (Multilink,
      Panavia F, RelyX U100), b) surface conditioning (no conditioning as control
      group; Metal/Zirconia Primer; air abrasion + Metal/Zirconia Primer; Si-based
      nanofilm + Monobond s); c) aging (no aging vs thermocycling at 5 degrees C to 55
      degrees C, 6000 cycles). The nanofilm was deposited by direct current using
      argon/oxygen plasma (8:1 in flux) on the zirconia surface. Resin cements were
      bonded to zirconia surfaces using polyethylene molds. The shear bond strength
      (SBS) test was performed using a universal testing machine (1 mm/min), and after
      debonding, the substrate and adherent surfaces were analyzed using optical and
      scanning electron microscopes to categorize the failure types. The data were
      statistically evaluated using 3-way ANOVA and Tukey's test (5%). RESULTS: Resin
      cement type (p < 0.05), surface conditioning method (p < 0.05), and aging
      condition (p < 0.05) had a significant effect on the bond strength results.
      Interactions were also significant (p < 0.05). In the nonaged condition, while
      control groups presented the lowest results with all cements (0 to 5.2 MPa), the
      airabraded group in combination with RelyX U100 resulted in the highest SBS (21.8
      +/- 6.7 MPa). After aging, the SBS results decreased in the air-abraded groups
      for all cements (4.54 to 9.44 MPa) and showed no statistical significance
      compared to the Si-based nanocoated groups (4.24 to 6.44 MPa). After air-abrasion
      and primer application, only Panavia F and RelyX U100 cements showed exclusively
      mixed failures, but after nanofilm coating and silanization, all cements showed
      exclusively mixed failures with and without aging. CONCLUSION: Chemical adhesion
      of the resin cements tested to zirconia was similar after silica-based nanofilm
      deposition and air abrasion followed by primer application.

PMID- 23534026
TI  - Effect of water temperature on cyclic fatigue properties of glass-fiber
      reinforced hybrid composite resin and its fracture pattern after flexural
      testing.
AB  - PURPOSE: To evaluate in vitro the influence of dynamic loading applied to a glass
      fiber-reinforced hybrid composite resin on its flexural strength in a moist,
      simulated oral environment. MATERIALS AND METHODS: Three-point flexural strength
      specimens were subjected to cyclic loading in water at 37 degrees C and 55
      degrees C to investigate the influence of immersion temperature on impact fatigue
      properties. Specimens were subjected to cyclic impact loading at 1 Hz for up to 5
      * 105 cycles to obtain the number of cycles to failure, the number of unbroken
      specimens after 5 * 105 cycles, and the residual flexural strength of unbroken
      specimens. Maximum loads of 100, 200, and 300 N were chosen for both the non
      reinforced and the glass-fiber reinforced hybrid composite resins. RESULTS: The
      mean residual flexural strength for 100 N impact loading at temperatures of 37
      degrees C and 55 degrees C was 634 and 636 MPa, respectively. All specimens
      fractured at fewer than 5 * 105 cycles for loads of 200 and 300 N. CONCLUSION:
      Reduced numbers of cycles to fracture and lower fatigue values were observed as
      both the maximum load and immersion temperature increased.

PMID- 23534027
TI  - A prospective cohort study on cast-metal slot-retained resin-bonded fixed dental
      prostheses in single missing first molar cases: results after up to 7.5 years.
AB  - PURPOSE: To evaluate under controlled clinical conditions the outcomes of cast
      metal slot-retained resin-bonded fixed dental prostheses (RBFDPs) in which resin
      composite interlocked the restoration retainers in place after cementation in
      cases with single missing first molars, and to collect survival data on this
      esthetic RBFDP design combined with an economical metal fit-surface treatment
      method and resin luting system. MATERIALS AND METHODS: Forty-one tub-shaped inlay
      retained RBFDPs were clinically observed for up to 7.7 years in 35 recipients of
      both genders between 18 and 52 years of age. Clinical examinations were performed
      at baseline and 6 and 12 months after restoration placement, and thereafter at
      regular 1-year intervals. Modified US Public Health Service (USPHS) parameters,
      sulcus bleeding index, Silness-Loe plaque index, pocket depths, tooth mobility,
      pulp vitality, and periapical radiographs regarding the abutment teeth were
      assessed at these follow-up appointments. The Kaplan-Meier survival estimation
      method was performed to detect the overall and functional survival rates and mean
      survival times of the RBFDPs at the end of the study. The Breslow (Generalized
      Wilcoxon) test was used to evaluate the influence of restoration location and age
      and gender of the patient regarding the overall survival probability at the end
      of the follow-up (alpha = 0.05). RESULTS: At the end of the study, 34 RBFDPs
      (83%) were still functioning with a mean follow-up of 6.3 years. According to the
      Kaplan-Meier survival curve, the overall and functional survival probabilities
      were calculated as 76% and 83%, with mean survival times of 6.8 years and 7.2
      years, respectively. All clinical parameters monitored throughout the follow-up
      period predominantly revealed clinically acceptable results. Breslow test
      statistics presented nonsignificant differences with better results for the
      RBFDPs placed in the mandible of female recipients younger than 30 years of age.
      The most common failure noted with the RBFDPs was fracture of the occlusal
      veneering composite restoration over the retainer of a single abutment, leading
      to a predisposition of the restoration to partial debonding. CONCLUSION: Within
      the limitations of this prospective cohort study, it can be concluded that cast
      metal slot-retained RBFDPs utilizing the interlocking mechanism of a resin
      composite to obtain additional retention from the abutment cavities show
      acceptable clinical success rates, and can be considered a minimally invasive,
      economical, and time-saving treatment alternative for the prosthetic
      rehabilitation of single missing first molars.

PMID- 23534028
TI  - Shear bond strength of a novel silorane adhesive to orthodontic brackets and
      unprepared bovine enamel.
AB  - PURPOSE: To evaluate the suitability of a novel epoxy-based resin, Filtek
      Silorane, for orthodontic bracket bonding on unprepared enamel. MATERIALS AND
      METHODS: Shear forces to bovine enamel were measured for Filtek Silorane and
      Transbond XT in combination with steel, ceramic, and polymer brackets. For Filtek
      Silorane, etching was performed with the Silorane self-etching primer alone or an
      additional previous application of phosphoric acid. Transbond XT (conventional
      methacrylate) was used for the control group and the enamel was previously etched
      with 35% phosphoric acid. All samples were thermocycled (1000X, 5 degrees to 55
      degrees  C). Shear bond testing was done with an Instron 3344 at a crosshead
      speed of 1 mm/min. In addition, adhesive remnant index (ARI) scores were
      evaluated. RESULTS: The shear forces showed a weak adhesion of Filtek Silorane to
      unprepared enamel both with the selfetching primer and conventional etching (0.87
      to 4.28 MPa). The shear forces of the control group were significantly higher
      (7.6 to 16.5 MPa). The ARI scores showed a clear failure at the enamel/adhesive
      interface for all Filtek Silorane samples. For the combination of Transbond XT
      and different brackets, the failure was found at the adhesive/bracket interface.
      CONCLUSION: The novel epoxy-based resin Filtek Silorane is not appropriate for
      bonding of brackets to unprepared enamel.

PMID- 23534029
TI  - Effect of different surface treatments on adhesion of In-Ceram Zirconia to enamel
      and dentin substrates.
AB  - PURPOSE: Resin bonding of In-Ceram Zirconia (ICZ) ceramics is still a challenge,
      especially for minimally invasive applications. This study evaluated the adhesion
      of ICZ to enamel and dentin after different surface treatments of the ceramic.
      MATERIALS AND METHODS: ICZ ceramic specimens (diameter: 6 mm; thickness: 2 mm) (N
      = 100) were fabricated following the manufacturer's instructions and randomly
      assigned to 5 groups (n = 20), according to the surface treatment methods
      applied. The groups were as follows: group C: no treatment; group SB:
      sandblasting; group SCS-S: CoJet+silane; group SCS-P: CoJet+Alloy Primer; group
      GE-S: glaze+ hydrofluoric acid etching (9.6%) for 60 s+silane. Each group was
      randomly divided into two subgroups to be bonded to either enamel or dentin (n =
      10 per group) using MDP-based resin cement (Panavia F2.0). All the specimens were
      subjected to thermocycling (5000x, 5 degrees C-55 degrees C). The specimens were
      mounted in a universal testing machine and tensile force was applied to the
      ceramic/cement interface until failure occurred (1 mm/min). After evaluating all
      the debonded specimens under SEM, the failure types were defined as either
      "adhesive" with no cement left on the ceramic surface (score 0) or "mixed" with
      less than 1/2 of the cement left adhered to the surface with no cohesive failure
      of the substrate (score 1). The data were statistically evaluated using 2-way
      ANOVA and Tukey's tests (alpha = 0.05). RESULTS: The highest tensile bond
      strength for the enamel surfaces was obtained in group GE-S (18.1 +/- 2 MPa) and
      the lowest in group SB (7.1 +/- 1.4 MPa). Regarding dentin, group CSC-P showed
      the highest (12 +/- 1.3 MPa) and SB the lowest tensile bond strength (5.7 +/- 0.4
      MPa). Groups SB, CSC-S, CSC-P, and GE-S did not show significant differences
      between the different surface treatments on either enamel or dentin surfaces (p <
      0.05, p < 0.001, respectively). Groups CSC-P and GE-S presented similar bond
      strength for both the enamel and dentin substrates (p < 0.8 and p < 0.9),
      respectively. While on enamel substrates, exclusively adhesive failures from ICZ
      (score 0) were found, on dentin exclusively mixed failures were observed (score
      1). CONCLUSION: Adhesion of ICZ to both enamel and dentin can be improved when
      ceramics are glazed, etched, and silanized, or sandblasted, primed, and cemented
      with an MDP-based cement.

PMID- 23534030
TI  - Effect of artificial aging on the bond durability of fissure sealants.
AB  - PURPOSE: To evaluate the effect of artificial aging on the bond durability of
      fissure sealants in vitro. MATERIALS AND METHODS: Twenty bovine incisors received
      4 different sealant treatments and were divided into four groups: 1. Ultraseal XT
      plus (UX); 2. Enamel Loc (EL); 3. 35% phosphoric acid plus Enamel Loc (PEL); 4.
      Adper Prompt L-Pop plus Clinpro (PPC). Beam-shaped specimens were prepared and
      randomly divided into three subgroups. One subgroup underwent the microtensile
      bond strength (uTBS) test after 24-h storage in 37 degrees C water. The other two
      subgroups were also subjected to the microtensile bond strength test after 5000
      and 10,000 thermal cycles, respectively. Another twelve intact human third molars
      were sealed using 1 of 3 methods and were divided into 3 groups of 4 each: 1.
      Ultraseal XT plus; 2. Adper Prompt L-Pop plus Clinpro; and 3. Enamel Loc. Two
      specimens from each group were immersed in a 50% silver nitrate solution for 24
      h, followed by exposure to fluorescent light for 8 h, before being scanned in a
      micro-CT (microcomputer tomography) machine. The other two were handled in the
      same way after undergoing 10,000 thermal cycles. The CT images obtained were
      evaluated. RESULTS: All samples from the EL group were broken during preparation,
      so no uTBS results were available. After 5000 thermal cycles, the bond strengths
      of the three other groups (UX, PEL, PPC) decreased significantly (p < 0.05).
      Longer thermocycling (10,000 cycles) resulted in more decreases in uTBS for group
      PEL and PPC, while the strength of the UX group remained relatively unchanged.
      After thermocycling, considerable silver penetration could be seen at the
      sealant/enamel interface of the EL group in micro-CT images. CONCLUSIONS: The
      etch-and-rinse procedure for sealant application promotes higher bond strength
      under artificial aging. Micro-CT, a nondestructive analytical tool, may be used
      to evaluate the sealant/enamel interface effectively.

PMID- 23534031
TI  - Resin-dentin bonds of etch-and-rinse adhesives to alcohol-saturated acid-etched
      dentin.
AB  - PURPOSE: To evaluate the effect of the alcohol wet-bonding technique on bond
      performance of the adhesive interface produced by two-step etch-and-rinse
      adhesive systems. MATERIALS AND METHODS: Composite buildups were bonded to
      sectioned human third molars using Adper Single Bond 2 (SB) bonded to acid-etched
      dentin saturated with water (control) or ethanol, or XP Bond (XP) bonded to acid
      etched dentin saturated with water (control) or tert-butanol. A simplified dentin
      dehydration protocol was performed using 100% ethanol or 99.5% tert-butanol
      directly applied to dentin for 60 s. Specimens were cut into nontrimming dentin
      composite beams that were divided equally in two subgroups: immediately tested
      and after immersion in 10% NaOCl solution for 1 h. Specimens were tested in
      tension at a crosshead speed of 1 mm/ min until failure, and the failure mode was
      evaluated. Data were statistically analyzed with three-way ANOVA and Tukey's test
      (alpha = 0.05). Additional dentin disks were bonded using the same groups tested
      and examined for leakage under light microscopy after immersion in ammoniacal
      silver nitrate solution. RESULTS: The SB control group showed significantly
      higher bond strength values than did SB used on ethanol saturated dentin (p <
      0.05); this tendency was confirmed by the silver nitrate deposition. The use of
      tert-butanol did not influence XP bond strength values (p > 0.05) or silver
      nitrate penetration. NaOCl solution significantly reduced the bond strength of
      all groups tested (p < 0.05) and also increased the interfacial silver nitrate
      penetration. CONCLUSION: The simplified alcohol wet-bonding technique used in the
      present study was not able to improve resin/dentin bond performance for
      simplified etch-and-rinse adhesive systems.

PMID- 23534032
TI  - Long-term bond of glass ceramic and resin cement: evaluation of titanium
      tetrafluoride as an alternative etching agent for lithium disilicate ceramics.
AB  - PURPOSE: To evaluate in vitro the effect of using titanium tetrafluoride as an
      alternative etchant prior to the silanization of the bonding surface on the long
      term resin bond strength to lithium disilicate ceramic. MATERIALS AND METHODS:
      Disk-shaped specimens made of lithium disilicate ceramic were ground with
      abrasive paper, then etched with aqueous solutions (2.5% and 5%) of titanium
      tetrafluoride for 60 s, 120 s and 240 s. Positive control specimens were etched
      with 5% hydrofluoric acid for 20 s and negative control specimens were not
      etched. Afterwards, bonding surfaces of all specimens were silanized. Plexiglas
      tubes filled with a composite resin were bonded to the specimens using an
      alignment apparatus and a composite luting resin. After storage in 37 degrees C
      tap water for three days (n = 8) and after storage in 37 degrees C tap water for
      150 days interrupted by 5 x 7500 thermal cycles (n = 8), tensile bond strength
      (TBS) was measured in a universal testing machine at a crosshead speed of 2
      mm/min. RESULTS: After artificial aging, all specimens etched with titanium
      tetrafluoride debonded spontaneously resulting in a TBS of 0 MPa. Therefore,
      statistical analysis revealed a highly significant difference between the
      positive control and the test groups after 150 days storage. CONCLUSION: Etching
      the bonding surface of lithium disilicate ceramic restorations with hydrofluoric
      acid is still a "gold standard" and cannot be replaced by titanium tetrafluoride.

PMID- 23534033
TI  - Combating child abuse: the role of a dentist.
AB  - BACKGROUND AND PURPOSE: Child abuse has serious physical and psychosocial
      consequences which adversely affect the health and overall well-being of a child.
      However, in a developing country like India there has been no knowledge of the
      extent, magnitude and trends of the problem. This study reviews the overall
      scenario of child abuse in India as well as the role of the dentist in
      recognising and thereby combating this problem. RESULTS: Among health
      professionals, dentists are probably in the most favourable position to recognise
      child abuse, with opportunities to observe and assess not only the physical and
      the psychological condition of the children, but also the family environment. The
      high frequency of facial injuries associated with physical abuse places the
      dentist at the forefront of professionals to detect and treat an abused child.
      Screening for maltreatment should be an integral part of any clinical examination
      performed on a child. Although many injuries are not caused by abuse, dentists
      should always be suspicious of traumatic injuries. The dental professional's role
      in child abuse and neglect is to know the current state law regarding reporting
      child abuse and to follow the law. Awareness, identification, documentation and
      notification should be carried out by the dentist. CONCLUSION: Paediatric
      dentists can provide valuable information and assistance to physicians about oral
      and dental aspects of child abuse and neglect. Such efforts will strengthen the
      ability to prevent and detect child abuse and neglect and enhance care and
      protection for the children.

PMID- 23534034
TI  - Correspondence between conventional and digitised radiographs for assessment of
      marginal bone.
AB  - PURPOSE: To compare reproducibility of marginal bone measurements in conventional
      film and digitised radiographs and to assess whether variations in
      reproducibility occurred in measurements taken in a longitudinal, epidemiological
      survey. MATERIALS AND METHODS: Triplicate measurements of the marginal bone level
      and of remaining bone were obtained from film and digitised full-mouth
      radiographic surveys from 20 individuals who were examined three times at five
      year intervals in a longitudinal study design. The digitalisation of the films
      was conducted by scanning the film with a flatbed scanner. The standard deviation
      (SD) of the triplicate measurements served as the statistic for reproducibility.
      The time spent for recording one radiographic survey, which consisted of 14
      periapicals and 2 bitewings, was documented. RESULTS: Statistically significant
      differences existed in the reproducibility of marginal bone level measurements
      obtained at the first examination and the two subsequent examinations both for
      film and digitised radiographs (P < 0.05). The difference in marginal bone level
      measurements (film vs digitised) was 0.16 mm (SD = 0.45 mm). Similarly, the
      overall difference in measurements of the remaining bone was 0.12 mm (SD = 0.61
      mm). Recording of a digitised survey lasted on average 5 min (SD = 1.5 min),
      while the recording of a film survey lasted on average 14 min (SD = 1 min).
      CONCLUSIONS: Digitising film is an acceptable method for the purpose of assessing
      the marginal bone level and will save time in longitudinal, epidemiological
      studies.

PMID- 23534035
TI  - Have CONSORT guidelines improved the quality of reporting of randomised
      controlled trials published in public health dentistry journals?
AB  - PURPOSE: To assess a) whether the quality of reporting of randomised controlled
      trials (RCTs) has improved since the formulation of the Consolidated Standards of
      Reporting Trials (CONSORT) statement and b) whether there is any difference in
      reporting of RCTs between the selected public health dentistry journals.
      MATERIALS AND METHODS: A hand search of the journals of public health dentistry
      was performed and four journals were identified for the study. They were
      Community Dentistry and Oral Epidemiology (CDOE), Community Dental Health (CDH),
      Journal of Public Health Dentistry (JPHD) and Oral Health and Preventive
      Dentistry (OHPD). A total of 114 RCTs published between 1990 and 2009 were
      selected. CONSORT guidelines were applied to each selected article in order to
      assess and determine any improvement since the publication of CONSORT guidelines.
      The chi-square test was employed to determine any statistical significant
      difference in quality of reporting of RCTs before and after the publication of
      the CONSORT guidelines. A comparison was also done to determine any statistically
      significant difference in quality of reporting of RCTs between the selected
      journals. RESULTS: Title, abstract, discussion and conclusion sections of the
      selected articles showed adherence to the CONSORT guidelines, whereas the
      compliance was poor with respect to the methodology section. CONCLUSION: The
      quality of reporting of RCTs is generally poor in public health dentistry
      journals. Overall, the quality of reporting has not substantially improved since
      the publication of CONSORT guidelines.

PMID- 23534036
TI  - Impact of oral health behaviours and oral habits on the number of remaining teeth
      in older Taiwanese dentate adults.
AB  - PURPOSE: To evaluate the impact of oral health behaviours and oral habits on the
      number of remaining teeth in older Taiwanese dentate adults. SUBJECTS AND
      METHODS: Subjects comprised dentate patients (mean age, 60.0 +/- 9.9 years) in
      Taiwan. Information on demographic data, oral health behaviours, oral habits and
      self-perceived health status was collected via self-administered questionnaires
      and dentition status was assessed by oral examination. Multiple logistic
      regression analyses were used to determine variables correlated with the low
      dentition group (subjects with less than 20 natural teeth or 8 functional tooth
      units). RESULTS: The analysis showed that the low dentition group was more likely
      to be older and to exhibit low educational levels, less frequent use of dental
      floss, more common smoking habits, poor self-perceived dental health and to be
      exbetel- nut chewers. In addition, the low dentition group was less likely to be
      current betel-nut chewers. CONCLUSIONS: These results underscore the importance
      of the use of dental floss and confirm the adverse effects of smoking on dental
      health. Hence, the dental profession should continue to encourage proper oral
      health behaviours and oral habits.

PMID- 23534037
TI  - Effects of tongue coating and oral health on halitosis among dental students.
AB  - PURPOSE: To assess halitosis and determine the relationship between halitosis and
      tongue scores, periodontal status and DMFT among dental students. MATERIALS AND
      METHODS: The study comprised 268 (178 female, 90 male) dental students. Halitosis
      was measured using a Halimeter and the organoleptic method. Halitosis was
      diagnosed with a mean volatile sulphur compounds (VSC) level of >=125 ppb and an
      organoleptic measurement of >= 2 on a 0- to 5-point scale. Tongue scores were
      obtained using a tongue coating index (TCI), periodontal status was measured and
      assessed using the Community Periodontal Index of Treatment Needs (CPITN) and
      DMFT indices were calculated. RESULTS: Halitosis occurred at higher rates among
      male students than female students (83% vs 71%, P = 0.02). No differences were
      found in halitosis rates among students in different academic years (P = 0.6) or
      age groups (P = 0.6). A relationship was found between halitosis and tongue
      scores (P < 0.001) and between halitosis and mean CPITN scores (P = 0.004). The
      mean DMFT was 4.02 (SD = 3). No relationship was found between halitosis and DMFT
      index (P = 0.5). CONCLUSION: Halitosis was prevalent among dental students. Given
      their responsibilities for diagnosing and improving oral health, they may benefit
      from increased awareness of the problem and encouragement to improve their own
      oral hygiene, especially male students.

PMID- 23534038
TI  - Traumatic dental injuries among 12-year-old schoolchildren in Jordan: prevalence,
      risk factors and treatment need.
AB  - PURPOSE: To assess the prevalence and related factors of traumatic dental
      injuries (TDI) among 12-year-old Jordanian schoolchildren. MATERIALS AND METHODS:
      For this cross-sectional study among schoolchildren, a sample of 2560
      schoolchildren (1209 boys, 1351 girls) aged 12 years were randomly selected. The
      epidemiological classification adopted by the World Health Organization (WHO) and
      modified by Andreasen et al was used to record TDI on incisors. RESULTS: Of the
      children examined, 5.5% showed TDI. The difference in prevalence between boys and
      girls was statistically significant (P < 0.01). Maxillary central incisors were
      the most affected and the most common type of crown injury was enamel/dentin
      fracture. The relationship between dental injuries and geographic location, area,
      and socioeconomic indicators was not statistically significant. Most of the TDI
      occurred at home, followed by school; the most frequent cause was falls. No
      statistically significant association was found between TDI and dental caries
      experience (P > 0.05). There was a tendency for boys (P < 0.01), children with an
      incisal overjet > 3 mm (P < 0.01) and incompetent lip closure (P < 0.001) to have
      experienced dental injuries. Treatment need due to dental injuries was very high.
      CONCLUSION: The prevalence of traumatic injuries to permanent incisors in 12-year
      old Jordanian schoolchildren was relatively low. TDI was associated with gender,
      overjet and lip competence, but was not influenced by dental caries experience.
      There was a great unmet treatment need.

PMID- 23534039
TI  - Prevalence of taurodontism and its association with various oral conditions in an
      Indian population.
AB  - PURPOSE: The aim of this retrospective study was to assess the prevalence of
      taurodont molars among an Indian population. The goal was also to determine
      sexual dimorphism, distribution of taurodontism as well as any association
      between taurodontism and simultaneously occurring syndromes and anomalies.
      MATERIALS AND METHODS: Full-mouth periapical radiographs of a total of 1360
      patients were screened. A total of 9792 molars (including third molars) were
      evaluated. The relative incidence and the correlations regarding the location of
      taurodonts (right versus left side and maxillary versus mandibular) were analysed
      using the Z test. RESULTS: The overall incidence of subjects with taurodont
      molars among this Indian population was 2.5% (34/1360). Sexual distribution
      showed female dominance (21 females, 13 males), but this was statistically
      insignificant (P > 0.05). Maxillary second molars (35/118) were the most commonly
      involved teeth, followed by mandibular second molars (32/118). No significant
      differences were obtained for distribution by side (right vs left; P > 0.05) or
      interarch distribution (maxillary vs mandibular; P > 0.05). Out of 34 subjects
      with taurodonts, 50% (17/34) were associated with pyramidal molars and 32.35%
      (11/34) had impacted molars. CONCLUSIONS: Taurodontism is not uncommon in the
      Indian population and it might be associated with other conditions, such as
      pyramidal molars and impaction. Further larger scale studies are required to
      assess its prevalence in the general population and to establish any
      associations.

PMID- 23534040
TI  - Dental anxiety in children with cleft lip and palate: a pilot study.
AB  - PURPOSE: To investigate the level of dental fear and anxiety of children who have
      cleft lip and palate (CLP). MATERIALS AND METHODS: The study was performed at
      Cukurova University, Faculty of Dentistry. A total of 32 7- to 12-yearold
      children, 17 of them with CLP (8 girls and 9 boys) and 15 of them without CLP (7
      girls and 8 boys) participated in the study. The children were evaluated by using
      the Facial Image Scale (FIS) and Dental Subscale of Children's Fear Survey
      Schedule (CFSS-DS) methods. The anxiety state of the children was assessed twice
      using FIS: first in the dental hospital waiting room (FIS-WR) and after, while
      sitting in the dental chair (FIS-DC). CFSS-DS was administered to all
      participants in order to assess the dental anxiety while they were sitting in the
      dental chair. RESULTS: According to the FIS results, there was no difference
      between CLP and control group in the waiting room (P = 0.682). However, the CLP
      group showed lower scores than the control group while they were sitting in the
      dental chair (P = 0.030). The FIS scores of the CLP group were significantly
      higher in the waiting room than while sitting in the dental chair (P = 0.007). In
      the control group, there was no significant difference between FIS-WR and FIS-DC
      values (P = 0.664). The total CFSS-DS scores of children with CLP were lower than
      those of the control group, but these differences were not statistically
      significant (P > 0.05). CONCLUSION: Children with CLP showed more anxiety in the
      FIS-WR than in the FIS-DC, but they showed lower scores than the control group in
      the FIS-DC. The positive previous experience of meetings with dentists of the CLP
      children could explain these results. Positive previous experiences with dentists
      and a short time in the waiting room could be key elements in the care of CLP
      children.

PMID- 23534041
TI  - Current and future research in diagnostic criteria and evaluation of caries
      detection methods.
AB  - The biochemical definition of dental caries is reasonably understood and
      generally agreed upon, but there is no consensus on a clinical definition among
      dentists. There are many proposed diagnostic criteria of dental caries in the
      dental literature. The recently developed International Caries Detection and
      Assessment System (ICDAS II) has been constructed to allow data comparison
      between studies. It can be used in epidemiological studies, public health
      research, clinical research, clinical practice and dental education. A good study
      evaluating a caries detection method should contain information on caries
      prevalence of the study sample and other measures, including sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV).
      It is noteworthy that measuring sensitivity and specificity provides no
      quantitative information on how likely a tested tooth is to be carious because
      the true caries status of the tooth is not known in a clinical situation.
      Moreover, the study design for caries detection should address the interpretation
      of predictive values because PPV and NPV are affected by the caries prevalence.
      The study design should also measure patient-oriented outcomes, address
      allocation concealment and avoid lead-time bias to generate valid and clinically
      relevant studies. Prudent evaluation of caries detection methods is the standard
      of care. This paper reviews current diagnostic criteria for caries detection and
      discusses proper ways to evaluate new diagnostic methods.

PMID- 23534042
TI  - The effects of asthma and asthma medication on dental caries and salivary
      characteristics in children.
AB  - PURPOSE: To investigate the prevalence and severity of dental caries in children
      with a history of asthma in addition to their salivary characteristics, flow rate
      and buffering capacity, as well as the salivary level of Mutans streptococci (MS)
      and lactobacilli present. MATERIALS AND METHODS: The study sample was composed of
      30 cases and 30 controls with an age range from 5 to 13 years. The cases involved
      children with a past history of asthma, while the controls were medically fit
      children. The study was conducted from 2010 to 2011 and patients were randomly
      selected through the electronic filing system at King Abdul-Aziz University
      Hospital (R4 system), Jeddah, Saudi Arabia. Interviews and questionnaires were
      completed by the parents of the children involved and dental examinations were
      performed. Stimulated salivary samples were collected to determine the salivary
      flow rate, buffering capacity and salivary levels of MS and lactobacilli.
      RESULTS: No significant differences were found in the DMFT, dmft scores or
      community periodontal index (CPI) scores between the cases and controls. However,
      there was a positive correlation between DMFT and dmft scores (r = 0.83, P <
      0.0001) in both the cases and controls. In asthmatic patients who took their
      medication 3 times a day or more, the level of MS and lactobacilli was
      significantly higher (P = 0.014 and P = 0.008, respectively) compared with other
      asthmatic patients. Patients with severe asthma had significantly lower salivary
      flow rate levels than other asthmatic patients (P = 0.040), while patients taking
      a combination therapy of anti-asthmatic drugs with corticosteroids had higher
      levels of lactobacilli compared with patients using other medications (P = 0.02).
      CONCLUSIONS: The frequency of taking asthma medication, the severity of asthma
      and the use of combination therapy can significantly alter the salivary
      characteristics in asthmatic children.

PMID- 23534043
TI  - Assessing the oral health-related quality of life in Iranian adolescents:
      validity of the Persian version of the Child Oral Health Impact Profile (COHIP).
AB  - PURPOSE: To evaluate the psychometric properties of an oral-health related
      quality of life (OHRQoL) instrument for application in the population of Iranian
      adolescents and to assess the discriminate and convergent validity and
      reliability of the Persian version of the Child Oral Health Impact Profile
      (COHIP) in a representative sample of this population. MATERIALS AND METHODS:
      Using multistage stratified sampling, 597 schoolchildren aged from 13 to 18 years
      living in the city of Isfahan were recruited to complete the Persian COHIP
      questionnaire. They were also examined for dental caries and malocclusion by two
      trained, calibrated examiners. RESULTS: Overall COHIP scores ranged from 15 to
      135 (mean +/- SD: 103.6 +/- 18). Sixty-six percent of the students experienced at
      least one frequent oral health-related impact over the past three months. The
      Cronbach alpha coefficient was 0.89 for the overall score. Discriminate validity
      was supported by the significant difference between COHIP scores in the caries
      free group and the others (P = 0.01). In addition, the questionnaire was able to
      differentiate among the groups by various degrees of need for orthodontic
      treatment (P < 0.01). Convergent validity was confirmed by significant
      association between the quality of life scores, the self-perceived health and
      oral health ratings and the self-perceived treatment need (r = 0.36, 0.57, 
      0.40). CONCLUSION: The Persian COHIP demonstrated acceptable psychometric
      properties for the descriptive purposes. Some discrepancies observed between the
      clinical data and quality of life status were confirmed by the perceptual
      identity of such indices influenced by several overt and covert variables.

PMID- 23534044
TI  - The effect of docosahexaenoic acid (DHA) on expression of IL-1beta, IL-6, IL-8,
      and TNF-alpha in normal and lipopolysaccharide (LPS)-stimulated macrophages.
AB  - OBJECTIVE: Differentiated macrophages (MO) are the resident tissue phagocytes and
      sentinel cells of the innate immune response. These cells are major constituents
      of periapical granulomas. Current studies indicate these activated cells as the
      source of bone-resorbing cytokines in the periapical granuloma. Periapical
      inflammation can be mediated by proinflammatory cytokines like interleukin 1beta
      (IL-1beta), tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-8. Reducing the
      production of these cytokines may be beneficial for the treatment of periapical
      lesions. Oils rich in omega-3 fatty acids like docosahexaenoic acid (DHA) have
      been linked with anti-resorptive and bone-protective effects. The purpose of this
      investigation was to study the effect of DHA on the expression of these cytokines
      by normal and lipopolysaccharide (LPS)-treated MO. We hypothesized that
      pretreatment of MO with DHA decreases the expression of pro-inflammatory
      cytokines induced by LPS-treated MO. METHOD AND MATERIALS: THP-1 monocytes were
      cultured and differentiated into MO. DHA was added to MO in a dose-dependent
      manner. MO samples were added to the following groups: Group 1, ethanol alone as
      a solvent control; Group 2, 10 ug/ml of DHA (D1); Group 3, 20 ug/ml of DHA (D2);
      Group 4, 10 ug/ml of DHA + LPS (DL1); Group 5, 20 ug/ml of DHA + LPS (DL2); Group
      6, LPS alone. Reverse transcriptase-PCR (RT-PCR) followed by ImageJ analysis was
      used to measure cytokine expression. RESULTS: The results show that IL-1beta and
      TNF-alpha levels for DL and DHA (basal) were significantly lower than the levels
      in LPS alone. IL-6 was increased in the DL groups. There was no significant
      change for IL-8. CONCLUSION: DHA at higher concentrations may selectively
      decrease proinflammatory cytokine production of IL-1beta and TNF-alpha. More
      studies are needed to verify the anti-inflammatory therapeutic action of agents
      like DHA omega-3 fatty acids.

PMID- 23534045
TI  - Use of calcium hydroxide in deep cavities of primary teeth.
AB  - OBJECTIVE: To perform a literature review on the clinical and/or laboratory
      performance of the use of calcium hydroxide in deep cavities of primary teeth.
      METHOD AND MATERIALS: Literature in professional journals and summaries of BBO,
      LILACS, and MEDLINE databases (2000 to 2010) linked to the Virtual Health Library
      and PUBMED were searched. The search strategies used included the following
      descriptors: "dental caries" and "dental cavity lining" and "primary tooth",
      "dental cavity lining" and "primary tooth" and "calcium hydroxide", "dental
      caries" and "dental cavity lining" and "primary tooth" and "calcium hydroxide".
      The abstracts were selected according to the following inclusion criteria:
      published between 2000 and 2010, English language, trial and/or laboratory
      studies or literature review, regarding the use of calcium hydroxide in deep
      cavities of primary teeth. The abstracts analysis was performed by two reviewers
      separately. Potentially relevant studies available in full were analyzed based on
      criteria for quality assessment and displayed on an evidence-based table.
      RESULTS: After reading the abstracts (N = 39), six were selected as a basis for
      developing the study. CONCLUSION: Analysis suggests that calcium hydroxide is an
      interesting alternative in the control of caries lesions of primary teeth with
      the possibility of significantly increasing the success of indirect pulp capping;
      however, it should not be considered a determining factor in the success of a
      restorative procedure.

PMID- 23534046
TI  - The in vivo efficacy of Fluorinex topical fluoridation treatment.
AB  - OBJECTIVE: This randomized, single-controlled study was performed to validate in
      vivo the efficacy of single Fluorinex treatment by examining fluoride
      incorporation into enamel using electron microscopy. METHOD AND MATERIALS: Twenty
      healthy participants referred for routine dental treatment which also required
      extractions of at least two teeth as part of their treatment plan were included
      in this study. For each participant, one randomly selected tooth was extracted
      and sent for blind electron microscopic fluoride assay (control, C). Next,
      following a single Fluorinex treatment, the second (test, T) tooth was extracted
      and sent for the same assay. Intra-individual and intergroup fluoride content
      comparisons were performed, between control and test teeth. RESULTS: Highly
      significant intra-individual and intergroup differences were found between the
      treated and untreated teeth. Fluoride atomic percent (at%) and weight percent
      (wt%) estimated least squares means of untreated group were found to be 0.56 and
      0.48, and in the treated group 17.35 and 14.35. This increase in fluoride at%
      [16.78 +/- 2.3 (SE)], was also significant statistically (P < .0001); likewise,
      the increase in fluoride wt % [13.86 +/- 1.97 (SE)] was similarly significant (P
      < .0001). The system was well tolerated by the participants with minimal
      transitional mild side effects. CONCLUSION: In vivo fluoride application using
      the active Fluorinex system resulted in a significant increase of fluoride
      content in the enamel of adult permanent teeth compared to untreated internal
      controls.

PMID- 23534047
TI  - Nonsurgical antimicrobial photodynamic therapy in moderate vs severe peri-implant
      defects: a clinical pilot study.
AB  - OBJECTIVE: Recent review articles have shown that open debridement is more
      effective in the treatment of peri-implantitis than closed therapy. However,
      surgery may result in marginal recession and compromise esthetics. The purpose of
      this study was to assess the efficacy of nonsurgical antimicrobial photodynamic
      therapy (aPDT) in moderate vs severe defects. METHOD AND MATERIALS: The study
      encompassed 16 patients with a total of 18 ailing implants. Ten of these implants
      showed moderate bone loss (< 5 mm; Group 1) and eight implants severe defects (5
      through 8 mm; Group 2). All implants received aPDT without surgical intervention.
      At baseline and 2 weeks, 3 months, and 6 months after therapy, peri-implant
      health was assessed including sulcus bleeding index (SBI), probing depth (PD),
      distance from implant shoulder to marginal mucosa (DIM), and clinical attachment
      level (CAL). Radiographic evaluation of distance from implant to bone (DIB)
      allowed comparison of peri-implant hard tissues after 6 months. RESULTS: Baseline
      values for SBI were comparable in both groups. Three months after therapy, in
      both groups, SBI and CAL decreased significantly. In contrast, after 6 months,
      CAL and DIB increased significantly in Group 2, not in Group 1. However, DIM
      values were not statistically different 6 months after therapy in both groups.
      CONCLUSION: Within the limits of this 6-month study, nonsurgical aPDT could stop
      bone resorption in moderate peri-implant defects but not in severe defects.
      However, marginal tissue recession was not significantly different in both groups
      at the end of the study. Therefore, especially in esthetically important sites,
      surgical treatment of severe peri-implantitis defects seems to remain mandatory.

PMID- 23534048
TI  - Treatment of a fused/geminated tooth: a multidisciplinary conservative approach.
AB  - OBJECTIVE: To report a multidisciplinary treatment of gemination/fusion of the
      left maxillary first incisor. CASE REPORT: An 11-year-old boy presented to our
      clinic with the chief complaint of an unpleasant appearance of his anterior
      teeth. Clinical and radiographic evaluation revealed gemination/fusion of the
      left maxillary first incisor combined with an Angle's Class II relationship
      (skeletal), retruded mandible, deep bite, short lower face height, and
      proclinaion of the maxillary incisors. The multidisciplinary approached treatment
      included orthodontic treatment engaged with root canal treatment of the left
      maxillary first incisor followed by periodontal surgical separation of the mesial
      root of the left maxillary first incisor and restoration of the crown using resin
      restoration. CONCLUSION: Tooth shape anomalies in general dental practice may be
      rare, but the dentist should be aware of the nature of the problems encountered
      and the specific treatment needs. The treatment may be complex and contain
      various treatment protocols that may include interdisciplinary endodontic,
      surgical, and periodontal interventions.

PMID- 23534049
TI  - Effect of various fixation parameters on strain development of screw- and cement
      retained implant-supported restorations.
AB  - OBJECTIVE: The objective of this study was to quantify the potential effects of
      screw- and cement-retention on strain development of implant-supported fixed
      dental prostheses (FDPs). METHOD AND MATERIALS: A total of 20 single crowns and
      70 three-unit FDPs were fabricated to fit an in vitro model situation with two
      implants. Using strain gauges attached to the model material adjacent to the
      implants, strain development of the restorations during fixation was recorded
      while the parameters cement type (provisional and definitive cement), cementation
      force (10 N and 100 N), and tightening torque (5 Ncm, 10 Ncm, and 15 Ncm) were
      varied. MANOVA with Pillai's trace was used for pairwise comparisons between
      groups (alpha = .05). RESULTS: Mean absolute strain development ranged from 5.11
      um/m for to 27.26 um/m for single crowns and from 16.46 um/m to 689.04 um/m for
      multi-unit restorations. Screw-retained single crowns exhibited significantly
      smaller strain development as compared to cement-retained single crowns (P =
      .009). The type of cement used seemed to have no effect on strain development of
      an FDP regardless of the cementation force applied (P = .064 and P = .605). An
      increase in tightening torque for screw-retained FDPs also had no effect on
      resulting strain development (P values ranging from .692 to .807). Nonuniform
      results were found when comparing screw- and cementretention as the retention
      mechanism for FDPs. CONCLUSION: Strain development seems to depend predominantly
      on the accuracy achieved during the fabrication process whereas the retention
      mechanisms themselves as well as their potential parameters only have a minor
      effect.

PMID- 23534050
TI  - Bleeding complications following Nd:YAG laser-assisted oral surgery vs
      conventional treatment in cardiac risk patients: a clinical retrospective
      comparative study.
AB  - OBJECTIVE: Thermal Nd:YAG laser energy is well known for the purpose of blood
      coagulation. However, little is known about the bleeding frequency following
      laser-assisted oral surgery in patients on coumarin drugs. Therefore, the purpose
      of this study was to compare retrospectively the frequency of bleeding
      complications following Nd:YAG laserassisted versus conventional local
      coagulation of blood in oral surgery. METHOD AND MATERIALS: In October 2002,
      minor oral surgical interventions were found to be indicated in a total of 45
      cardiac risk patients. In Group 1, blood coagulation was yielded in 24 patients
      with a Nd:YAG laser system, whereas in Group 2, treatment was performed in 21
      patients with conventional means of local hemostasis. All therapies were
      performed continuing anticoagulant therapy between November 2002 and March 2003.
      Clinical data were recorded retrospectively from patient charts in May 2007.
      RESULTS: In both Groups 1 and 2, a total of two bleeding complications were
      recorded. However, local re-interventions were sufficient for local hemostasis.
      CONCLUSION: These results indicate that Nd:YAG laser-assisted local hemostasis
      was not able to prevent bleeding complications completely. Within the limitations
      of this retrospective study it was concluded that in patients with anticoagulant
      treatment undergoing minor oral surgery, Nd:YAG laser-assisted local hemostasis
      is not superior to conventional methods of blood coagulation with respect to the
      frequency of bleeding complications.

PMID- 23534051
TI  - Conservative approach to restore the first molar with extensive destruction: A 30
      month follow-up.
AB  - The available options for restoring multiple surface cavities are: amalgam,
      composite resin, or indirect restorations. Adhesive system and intradentinal pin
      retained composite resin restorations should have a similar performance to pin
      retained amalgam, regarding resistance to support occlusal forces. Polymerization
      shrinkage is a major concern when performing direct posterior composite resin
      restorations and the incremental insertion technique can provide less stress and
      outstanding margin behavior. Intradentinal pins can potentially enhance composite
      resin's retention, while reducing gaps caused by polymerization shrinkage. This
      article reports a clinical case involving an extensive restoration on a posterior
      tooth with cusp loss that was successfully treated using an intradentinal pin and
      direct nano-hybrid composite resin restoration. 

PMID- 23534052
TI  - Clinical application of a digital method to improve the accuracy of color
      perception in toluidine blue stained oral mucosal lesions.
AB  - OBJECTIVE: Color perception is an important variable in detecting and assessing
      oral conditions. The aim was to investigate clinicians' perception of toluidine
      blue (Tblue) staining compared to digital color analysis, which may impact
      mucosal lesion detection, affect the decision to biopsy, and biopsy site
      selection. METHOD AND MATERIALS: Four oral lesions were stained with Tblue.
      Digital color analyses of eight areas on each image were completed and were
      considered as "gold standard" (GS). Twenty specialists ranked these areas
      according to their perceived intensity of blue stain in two sessions. RESULTS:
      Consistency between GS and observers rankings was 0.8791. However, more than half
      of the observers inaccurately perceived the intermediate blue tones. Overall
      interobserver agreement was 0.8714; stability between two sessions decreased to
      45% for intermediate tones. CONCLUSION: Assessing the equivocal blueness of an
      oral mucosal lesion in clinical settings may vary due to variation in visual
      perception. A digital method for objective color analysis in clinical practice
      may be used to eliminate this deficiency by implementing a mathematical formula.

PMID- 23534053
TI  - Minimally invasive microsurgical management of the necrotic, immature apex tooth:
      case report and treatment recommendations.
AB  - OBJECTIVE: The purpose of this case report is to introduce a minimally invasive
      microsurgical technique for the treatment of the necrotic, immature apex tooth in
      adult patients and to provide treatment recommendations. METHOD AND MATERIALS: A
      43-year-old male patient was diagnosed with chronic apical periodontitis
      associated with a necrotic, immature apex of the maxillary central incisor. A
      minimally invasive microsurgical approach was applied for the treatment of the
      periapical disease. The crown of the immature apex tooth was left intact.
      RESULTS: The 1-year follow-up radiograph revealed uneventful healing of the
      periradicular lesion while soft tissue healing was optimal. CONCLUSION: The
      minimally invasive microsurgical technique may provide a viable solution for the
      survival of challenging necrotic, immature apex tooth cases in adults. Proper
      case selection is mandatory for the success of this technique.

PMID- 23534054
TI  - Arrested pneumatization of the sphenoid sinus.
AB  - Arrested pneumatization of the sphenoid sinus is a normal anatomic variant which
      may be mistaken for pathology. Suspected cases of arrested pneumatization of the
      sphenoid sinus on cone beam CT and multidetector CT scans are presented.
      Pertinent imaging findings and differential diagnosis are discussed. 

PMID- 23534055
TI  - Synaptic mechanisms underlying rapid antidepressant action of ketamine.
AB  - Recent clinical studies have demonstrated that a single subpsychotomimetic dose
      of ketamine, an ionotropic glutamatergic N-methyl-D-aspartate (NMDA) receptor
      antagonist, produces a rapid antidepressant response in patients with major
      depressive disorder, with effects lasting up to 2 weeks. Despite enthusiasm about
      this unexpected efficacy of ketamine, its widespread use as a fast-acting
      antidepressant in routine clinical settings is curtailed by its abuse potential
      as well as possible psychotomimetic effects. However, the ability of ketamine to
      produce a rapid and long-lasting antidepressant response in patients with
      depression provides a unique opportunity for investigation of mechanisms that
      mediate these clinically relevant behavioral effects. From a mechanistic
      perspective, it is easy to imagine how activation of NMDA receptors may trigger
      cellular and behavioral responses; it is relatively more difficult, however, to
      envision how transient blockade of one of the key pathways for neuronal
      communication produces a persistent beneficial effect. The authors discuss recent
      work linking ketamine's mechanism of action to homeostatic synaptic plasticity
      processes activated after suppression of NMDA-mediated glutamatergic
      neurotransmission. They focus on their recent work demonstrating that ketamine
      mediated blockade of NMDA receptors at rest deactivates eukaryotic elongation
      factor 2 (eEF2) kinase, resulting in reduced eEF2 phosphorylation and
      desuppression of rapid dendritic protein translation, including BDNF (brain
      derived neurotrophic factor), which then contributes to synaptic plasticity
      mechanisms that mediate longterm effects of the drug. The authors also explore
      possible molecular strategies to target spontaneous neurotransmitter release
      selectively to help uncover novel presynaptic avenues for the development of fast
      acting antidepressants and possibly psychoactive compounds with effectiveness
      against other neuropsychiatric disorders.

PMID- 23534056
TI  - Psychopathology in adolescent offspring of parents with panic disorder, major
      depression, or both: a 10-year follow-up.
AB  - OBJECTIVE: The authors examined the specificity and course of psychiatric
      disorders from early childhood through adolescence in offspring of parents with
      confirmed panic disorder and major depressive disorder. METHOD: The authors
      examined rates of psychiatric disorders at 10-year-follow-up (mean age, 14 years)
      in four groups: offspring of referred parents with panic and depression (N=137),
      offspring of referred parents with panic without depression (N=26), offspring of
      referred parents with depression without panic (N=48), and offspring of
      nonreferred parents with neither disorder (N=80). Follow-up assessments relied on
      structured interviews with the adolescents and their mothers; diagnoses were
      rated present if endorsed by either. RESULTS: Parental panic disorder,
      independently of parental depression, predicted lifetime rates in offspring of
      multiple anxiety disorders, panic disorder, agoraphobia, social phobia, and
      obsessive-compulsive disorder. Parental depression independently predicted
      offspring bipolar, drug use, and disruptive behavior disorders. Parental panic
      and depression interacted to predict specific phobia and major depressive
      disorder. Phobias were elevated in all at-risk groups, and depression was
      elevated in both offspring groups of parents with depression (with or without
      panic disorder), with the highest rates in the offspring of parents with
      depression only. Parental depression independently predicted new onset of
      depression, parental panic disorder independently predicted new onset of social
      phobia, and the two interacted to predict new onset of specific phobia and
      generalized anxiety disorder. CONCLUSIONS: At-risk offspring continue to develop
      new disorders as they progress through adolescence. These results support the
      need to screen and monitor the offspring of adults presenting for treatment of
      panic disorder or major depressive disorder.

PMID- 23534058
TI  - Weakly ordered chiral alignment medium derived from 5'-GMP : guanosine.
AB  - A novel weakly ordered chiral lyotropic alignment medium, derived by the self
      assembly of guanosine 5'-monophosphate (5'-GMP):guanosine for scaling RDCs to
      desired strengths and for the discrimination of enantiomers, is reported. The
      preparation of this inexpensive mesophase is straightforward, requires less time
      (1 h), and is sustainable, reversible and tunable over a wide range of
      temperature (280-330 K) and concentration.

PMID- 23534059
TI  - Safe routes to school: a public health practice success story-Atlanta, 2008-2010.

PMID- 23534060
TI  - Response to letter regarding article, "Short- and long-term outcomes with drug
      eluting and bare-metal coronary stents: a mixed-treatment comparison Analysis of
      117,762 patient-years of follow-up from randomized trials".

PMID- 23534061
TI  - The Innovative Medicines Initiative moves translational immunology forward.
AB  - The Innovative Medicines Initiative (IMI) was established in 2008 as a public
      private partnership between the European Union and the European Federation of
      Pharmaceutical Industries and Associations with the mission to promote the
      development of novel therapies through collaborative efforts based on the concept
      of pre-competitive research. Several consortia supported by IMI are dedicated to
      immuno-inflammatory disorders, immune-based biopharmaceuticals and vaccines.
      Herein, we present the key principles underlying IMI, briefly review the status
      of projects related to translational immunology, and present future topics of
      interest to immunologists.

PMID- 23534057
TI  - Treatment course with antidepressant therapy in late-life depression.
AB  - OBJECTIVE: In order to assess the effect of gray matter volumes and cortical
      thickness on antidepressant treatment response in late-life depression, the
      authors examined the relationship between brain regions identified a priori and
      Montgomery-Asberg Depression Rating Scale (MADRS) scores over the course of an
      antidepressant treatment trial. METHOD: In a nonrandomized prospective trial, 168
      patients who were at least 60 years of age and met DSM-IV criteria for major
      depression underwent MRI and were enrolled in a 12-week treatment study.
      Exclusion criteria included cognitive impairment or severe medical disorders. The
      volumes or cortical thicknesses of regions of interest that differed between the
      depressed group and a comparison group (N=50) were determined. These regions of
      interest were used in analyses of the depressed group to predict antidepressant
      treatment outcome. Mixed-model analyses adjusting for age, education, age at
      depression onset, race, baseline MADRS score, scanner, and interaction with time
      examined predictors of MADRS scores over time. RESULTS: Smaller hippocampal
      volumes predicted a slower response to treatment. With the inclusion of white
      matter hyper-intensity severity and neuropsychological factor scores, the best
      model included hippocampal volume and cognitive processing speed to predict rate
      of response over time. A secondary analysis showed that hippocampal volume and
      frontal pole thickness differed between patients who achieved remission and those
      who did not. CONCLUSIONS: These data expand our understanding of the prediction
      of treatment course in late-life depression. The authors propose that the primary
      variables of hippocampal volume and cognitive processing speed, subsuming other
      contributing variables (episodic memory, executive function, language processing)
      predict antidepressant response.

PMID- 23534063
TI  - Abstracts of the 34th Annual Meeting of the American Brachytherapy Society. April
      18-20, 2013. New Orleans, Louisiana, USA.

PMID- 23534062
TI  - Reply: To PMID 23328073.

PMID- 23534064
TI  - Retraction. "Established and emerging pathogens in Ixodes ricinus ticks collected
      from birds on a conservation island in the Baltic Sea".

PMID- 23534065
TI  - Molecularly targeted therapies: mechanisms of resistance. Abstracts of the AACR
      (American Association for Cancer Research) Special Conference. May 9-12, 2012.
      San Diego, California, USA.

PMID- 23534066
TI  - Abstracts of the AACR (American Association for Cancer Research)-IASLC
      (International Association for the Study of Lung Cancer) Joint Conference on
      Molecular Origins of Lung Cancer: Biology, Therapy, and Personalized Medicine.
      January 8-11, 2012. San Diego, California, USA.

PMID- 23534067
TI  - Robert E. Scully, M.D.

PMID- 23534069
TI  - Retraction notice to "Removal of oxytetracycline (OTC) in a synthetic
      pharmaceutical wastewater by a sequential anaerobic multichamber bed reactor
      (AMCBR)/completely stirred tank reactor (CSTR) system: Biodegradation and
      inhibition kinetics" [Bioresource Technology 104 (2012) 100-110].

PMID- 23534068
TI  - Aleksander Talerman, M.D., Ph.D., F.R.C.Path.

PMID- 23534070
TI  - Abstracts of the 19th Annual Meeting of the International Society for Cellular
      Therapy. April 22-25, 2013. Auckland, New Zealand.

PMID- 23534071
TI  - Author's reply to den Hartog.

PMID- 23534072
TI  - Abstracts of the 45th Annual Meeting of the American Burn Association. April 23
      26, 2013. Palm Springs, California, USA.

PMID- 23534073
TI  - Abstracts of the Forty-first Annual Meeting of the International
      Neuropsychological Society. February 6-9, 2013. Waikoloa, Hawaii, USA.

PMID- 23534074
TI  - NICE guideline on lipid modification.

PMID- 23534075
TI  - From the archives. The cerebral arterial supply. By Charles E Beevor  MD, FRCP.
      Brain 1908; 30: 403-25.

PMID- 23534076
TI  - Abstracts of the 2009 Bone Marrow Transplantation Tandem Meetings. February 11
      15, 2009. Tampa, Florida, USA.

PMID- 23534087
TI  - [A review of last year].

PMID- 23534088
TI  - MALDI-TOF technology joins the resistance.

PMID- 23534089
TI  - LGC purchases bioanalytical services business from quotient bioresearch.

PMID- 23534091
TI  - Quintiles enter bioanalytical partnership with South Korean CRO.

PMID- 23534090
TI  - Researchers identify proteins in urine that may act as diagnostic biomarkers for
      Kawasaki disease.

PMID- 23534092
TI  - Personalized treatment options at a faster pace?

PMID- 23534093
TI  - Remodeling not necessary when adding doctors.

PMID- 23534094
TI  - Age-moderated effects of consequence and intent information on punishment: an
      intuitive prosecutorial interpretation.
AB  - In responding to wrongdoings, people simultaneously pursue the goals of social
      control and fairness to the wrongdoer. Social control necessitates stronger
      weighting of consequences than causes; fairness entails the opposite. The authors
      hypothesized that the developmental shift from overweighting consequence to
      overweighting intent when determining levels of punishment illustrates a shift
      from a default defender of the normative order to a motivated crusader of
      fairness to the wrongdoer. Thus, punishment should increase slightly for
      intentional wrongdoings but decrease substantially for accidental wrongdoings as
      people age. In an experiment on disciplinary action in Singapore, 9-, 13-, and 17
      year-olds learned about the consequences of and intentions behind wrongdoings by
      peers and predicted consistency of the same act in the future, assigned blame to
      the wrongdoers, and recommended punishment for them. Results supported hypotheses
      derived from a fair-but-biased-yet-correctible model of intuitive prosecutors.

PMID- 23534095
TI  - Effects of perceived long-term stress on subjective and objective aspects of
      memory and cognitive functioning in a middle-aged population-based sample.
AB  - The longitudinal effects of perceived stress on measures of memory and two other
      cognitive functions (word fluency, visuospatial ability) in a middle-aged sample
      (40-60 years, M age = 47.1 years, SD = 6.1 years; n = 192) were examined. A group
      describing themselves as stressed in general at baseline, and at follow-up
      measurement 5 and 10 years later (n = 96) was compared with a matched (age, sex)
      low-stress group (n = 96). The results revealed more depressive symptoms over
      time in the high-stress group. With regard to memory, a dissociation between
      subjective and objective measures was observed. Specifically, participants in the
      high-stress group rated their memory as worse over time as compared with
      controls, and reported a higher frequency of occurrence of everyday memory
      failures, effects partly independent of depressive symptoms. However, the groups
      did not differ in terms of objective episodic memory performance, word fluency or
      block design performance, with stable levels of performance over time regardless
      of perceived stress. The lack of effects of stress on cognitive performance is
      discussed in the light of factors such as stress level, age of the participants,
      and other individual difference factors.

PMID- 23534096
TI  - Centenarians' "holy" memory: is being positive enough?
AB  - The authors compared 18 centenarians' (M age = 100.1 years, SD = 1.8 years)
      recognition memory for emotional (positive, negative, and religious) pictures
      with 18 older adults (M age = 75.2 years, SD = 6.8 years). Participants observed
      a series of images that varied in emotional valence and meaning and were later
      asked to discriminate between old and new images in a series of pictures that
      included studied images as well as new images. Centenarians showed decreased
      recognition memory for positive and negative images items compared with older
      adults, F(1, 34) = 9.82, p < .01. In addition, a significant age by valence
      interaction was observed highlighting how centenarians remembered religious
      pictures better while older adults favoured positive information when only
      positive pictures were taken into consideration. Results are interpreted in terms
      of possible age-linked changes in meaningful goals that lead centenarians to
      focus on meaningful religious self-relevant information rather than simply on
      positive information.

PMID- 23534097
TI  - Narrative discourse and sociocognitive abilities of a child with Cri-du-Chat
      syndrome.
AB  - The authors investigated narrative competence, sociocognitive abilities and
      emotion comprehension in a 9-year-old child (FS) with Cri-du-Chat Syndrome (CdCS)
      who had only a mild mental delay and relatively preserved language. Considering
      that the production of narratives is a major step in development and in the
      acquisition of learning skills related to conceptual, linguistic, structural, and
      pragmatic knowledge, and in the development of psychological lexicon, that is,
      the ability to use theory of mind (ToM) processes also in atypical development,
      this case provided an opportunity to study aspects of this genetic syndrome never
      investigated before. The authors found that the child's performance on different
      stories was comparable to that of chronological age controls for several
      narrative and emotional competences and even better than that of mental age
      controls. However, her ability to reason was still incomplete according ToM; in
      fact, FS was able to express her mental states, but she was unable to understand
      emotions, specifically mixed emotions. This finding suggests that in CdCS
      children with a well-developed language narrative and emotional competence could
      be a point of strength for improving their social skills with important effects
      on their familiar and school life. Also in CdCS children with the typical poor
      developed language, the narrative discourse could be introduced in their
      communication by means of any type of alternative language (i.e., sign language
      or augmentative and alternative communication) to improve their social abilities
      and to reduce behavioral disorders due to the difficulty in expressing their
      personal experiences.

PMID- 23534098
TI  - Spatial short-term memory in children with nonverbal learning disabilities:
      impairment in encoding spatial configuration.
AB  - The authors investigated whether impaired spatial short-term memory exhibited by
      children with nonverbal learning disabilities is due to a problem in the encoding
      process. Children with or without nonverbal learning disabilities performed a
      simple spatial test that required them to remember 3, 5, or 7 spatial items
      presented simultaneously in random positions (i.e., spatial configuration) and to
      decide if a target item was changed or all items including the target were in the
      same position. The results showed that, even when the spatial positions in the
      encoding and probe phases were similar, the mean proportion correct of children
      with nonverbal learning disabilities was 0.58 while that of children without
      nonverbal learning disabilities was 0.84. The authors argue with the results that
      children with nonverbal learning disabilities have difficulty encoding relational
      information between spatial items, and that this difficulty is responsible for
      their impaired spatial short-term memory.

PMID- 23534099
TI  - Are emotion and mind understanding differently linked to young children's social
      adjustment? Relationships between behavioral consequences of emotions, false
      belief, and SCBE.
AB  - According to empirical findings, emotional knowledge and false belief
      understanding seem to be differently linked to social adjustment. However,
      whereas false belief is assessed through the capacity to identify its behavioral
      consequences, emotion tasks usually rely on the comprehension of facial
      expressions and of the situational causes of emotions. The authors examined if
      the documented relationship between social adjustment and emotion knowledge in
      children extends to the understanding of behavioral consequences of emotions.
      Eighty French-speaking preschoolers undertook false belief and consequence-of
      emotion tasks. Their social adjustment was measured by the Social Competence and
      Behavior Evaluation. Children's language ability, their parent's level of
      education, and the familial socioeconomic score were taken into account. Results
      showed that children's social adjustment was significantly predicted by their
      knowledge of emotion, but not by their understanding of false belief. The
      findings confirm the special status of emotion among mental states for social
      adaptation and specify which dimensions of adaptation to peers and adults are
      predicted by the child's emotion understanding. They also suggest that the
      distinction between mind and emotion understanding may be conceptual rather than
      methodological.

PMID- 23534100
TI  - Addressing the issues of management and quality.

PMID- 23534101
TI  - Data recording aids in acute admissions.
AB  - PURPOSE: Clinical data capture and transfer are becoming more important as
      hospital practices change. Medical record pro-formas are widely used but their
      efficacy in acute settings is unclear. This paper aims to assess whether pro
      forma and aide-memoire recording aids influence data collection in acute medical
      and surgical admission records completed by junior doctors.
      DESIGN/METHODOLOGY/APPROACH: During October 2007 to January 2008, 150 medical and
      150 surgical admission records were randomly selected. Each was analysed using
      Royal College of Physicians guidelines. Surgical record deficiencies were
      highlighted in an aide-memoire printed on all A4 admission sheets. One year
      later, the exercise was repeated for 199 admissions. FINDINGS: Initial assessment
      demonstrated similar data capture rates, 77.4 per cent and 75.9 per cent for
      medicine and surgery respectively (Z = -0.74, p = 0.458). Following the aide
      memoire's introduction, surgical information recording improved relatively, 70.5
      per cent and 73.9 per cent respectively (Z = 2.01, p = 0.045). One from 11 aide
      memoire categories was associated with improvement following clinical training.
      There was an overall fall in admission record quality during 2008-9 vs 2007-8.
      RESEARCH LIMITATIONS/IMPLICATIONS: The study compared performance among two
      groups of doctors working simultaneously in separate wards, representing four
      months' activity. PRACTICAL IMPLICATIONS: Hospital managers and clinicians should
      be mindful that innovations successful in elective clinical practice might not be
      transferable to an acute setting. ORIGINALITY/VALUE: This audit shows that in an
      acute setting, over one-quarter of clinical admission data were not captured and
      devices aimed at improving data capture had no demonstrable effect. The authors
      suggest that in current hospital practice, focussed clinical training is more
      likely to improve patient admission records than employing recording aids.

PMID- 23534102
TI  - Quality improvement tools for chronic disease care--more effective processes are
      less likely to be implemented in developing countries.
AB  - PURPOSE: Chronic disease services may be improved if care management processes
      (CMPs), such as disease-specific flowsheets and chronic disease registries, are
      used. The newly industrialized Gulf state health service has underdeveloped
      primary care but higher diabetes prevalence. This paper's aim is to investigate
      care management processes in United Arab Emirates (UAE) primary care clinics to
      explore these issues. DESIGN/METHODOLOGY/APPROACH: A cross-sectional survey using
      self-administered questionnaires given to family physicians and nurses attending
      a UAE University workshop was used to collect data. FINDINGS: All 38 participants
      completed the questionnaire: 68 per cent were women and 81 per cent physicians.
      Care management processes in use included: medical records, 76 per cent; clinical
      guidelines, 74 per cent; chronic disease care rooms, 74 per cent; disease
      specific flowsheets, 61 per cent; medical record audits, 57 per cent; chronic
      disease nurse-educators, 58 per cent; electronic medical records (EMR), 34 per
      cent; and incentive plans based on clinical performance, 21 per cent. Only 62 per
      cent and 48 per cent reported that flowsheets and problem lists, respectively,
      were completed by physicians. Responses to the open-ended question included using
      traditional quality improvement (QI) approaches such as continuing education and
      staff meetings, but not proactive systems such as disease registries and self
      management. RESEARCH LIMITATIONS/IMPLICATIONS: The study used a small, non-random
      sample and the survey instrument's psychometric properties were not collected.
      PRACTICAL IMPLICATIONS: Chronic disease care CMPs are present in UAE clinics but
      use is limited. Quality improvement should include disease registries, reminder
      tracking systems, patient self-management support and quality incentives.
      ORIGINALITY/VALUE: This report highlights the lag regarding adopting more
      effective CMPs in developing countries.

PMID- 23534103
TI  - Patients' satisfaction of service quality in Saudi hospitals: a SERVQUAL
      analysis.
AB  - PURPOSE: Saudi Arabian hospital performance, vis-a-vis patient satisfaction with
      service provision, has emerged as a key policy and planning concern. Keeping in
      view public and private hospital service quality, this article seeks to provide
      guidelines to the on-going Saudi Arabian health service reorganization, which
      emphasizes decentralization, bed-capacity expansion, research-based policymaking
      and initiatives in the health insurance sector. DESIGN/METHODOLOGY/APPROACH: The
      article outlines an empirical study that compares patient satisfaction with
      service quality in Saudi Arabian public and private sector hospitals. The authors
      employ a stratified random sample (1,000 inpatients) from five Saudi Arabian
      public and five private hospitals. Data were collected through questionnaire
      using the SERVQUAL scale. For reducing the language bias the questionnaire was
      translated into Arabic. The response rate was 74.9 percent. Data were analyzed
      using SPSS and appropriate descriptive and inferential statistical techniques.
      FINDINGS: Cronbach's alpha for five service-quality dimensions (tangibles,
      reliability, responsiveness, safety and empathy) were high and the SERVQUAL
      instrument proved to be reliable, valid and appropriate. The results showed that
      sex, education, income and occupation were statistically significant in
      influencing inpatients' satisfaction, and all the null hypotheses were rejected.
      Only inpatient age was not significant. PRACTICAL IMPLICATIONS: The study
      highlights service quality influence in the design of broader healthcare
      strategies for Saudi Arabian public and private hospitals. It demands that
      management researchers and analysts must identify regional service quality
      consistencies and related inpatient demographic indicators. ORIGINALITY/VALUE:
      The study offers some insights into, and guidance for, hospital quality assurance
      in Saudi Arabia in general and the urban hospital setting in the Middle-East in
      particular.

PMID- 23534104
TI  - Medication reconciliation service in Tan Tock Seng Hospital.
AB  - PURPOSE: Medication reconciliation is integral to every hospital. Approximately
      60 percent of all hospital medication errors occur at admission, intra-hospital
      transfer or discharge. Effectively and consistently performing medication
      reconciliation at care-interfaces continues to be a challenge. Tan Tock Seng
      Hospital (TTSH) averages 4,700 admissions monthly. Many patients are elderly (>
      65 years old) at risk from poly-pharmacy. As part of a medication safety
      initiative, pharmacy staff started a medication reconciliation service in 2007,
      which expanded to include all patients in October 2009. This article aims to
      describe the TTSH medication reconciliation system and to highlight common
      medication errors occurring following incomplete medication reconciliation.
      DESIGN/METHODOLOGY/APPROACH: Where possible, patients admitted into TTSH are seen
      by pharmacy staff within 24 hours of admission. A form was created to document
      their medications, which is filed into the case sheets for referencing purposes.
      Any discrepancies in medicines are brought to doctors' attention. Patients are
      also counseled about changes to their medications. Errors picked up were captured
      in an Excel database. FINDINGS: The most common medication error was prescribers
      missing out medications. The second commonest was recording different doses and
      regimens. The reason was mainly due to doctors transcribing medications
      inaccurately. RESEARCH LIMITATIONS/IMPLICATIONS: This is a descriptive study and
      no statistical tests were carried out. Data entry was done by different pharmacy
      staff, and not a dedicated person; hence, data might be under-reported. PRACTICAL
      IMPLICATIONS: The findings demonstrate the importance of medication
      reconciliation on admission. Accurate medication reconciliation can help to
      reduce transcription errors and improve service quality. ORIGINALITY/VALUE: The
      article highlights medication reconciliation's importance and has implications
      for healthcare professionals in all countries.

PMID- 23534105
TI  - Exploring patient satisfaction predictors in relation to a theoretical model.
AB  - PURPOSE: The aim is to describe patients' care quality perceptions and
      satisfaction and to explore potential patient satisfaction predictors as person
      related conditions, external objective care conditions and patients' perception
      of actual care received ("PR") in relation to a theoretical model.
      DESIGN/METHODOLOGY/APPROACH: A cross-sectional design was used. Data were
      collected using one questionnaire combining questions from four instruments:
      Quality from patients' perspective; Sense of coherence; Big five personality
      trait; and Emotional stress reaction questionnaire (ESRQ), together with
      questions from previous research. In total, 528 patients (83.7 per cent response
      rate) from eight medical, three surgical and one medical/surgical ward in five
      Norwegian hospitals participated. Answers from 373 respondents with complete ESRQ
      questionnaires were analysed. Sequential multiple regression analysis with ESRQ
      as dependent variable was run in three steps: person-related conditions, external
      objective care conditions, and PR (p < 0.05). FINDINGS: Step 1 (person-related
      conditions) explained 51.7 per cent of the ESRQ variance. Step 2 (external
      objective care conditions) explained an additional 2.4 per cent. Step 3 (PR) gave
      no significant additional explanation (0.05 per cent). Steps 1 and 2 contributed
      statistical significance to the model. Patients rated both quality-of-care and
      satisfaction highly. ORIGINALITY/VALUE: The paper shows that the theoretical
      model using an emotion-oriented approach to assess patient satisfaction can
      explain 54 per cent of patient satisfaction in a statistically significant
      manner.

PMID- 23534106
TI  - Cultural values and health service quality in China.
AB  - PURPOSE: Several service quality studies show how cultural features may influence
      the way service quality is perceived. However, few studies specifically describe
      culture's influence on health service quality. Also, there are few studies that
      take into account patients' health service quality perceptions. This article
      seeks to present a first step to fill these gaps by examining patients' cultural
      values and their health service quality assessments. DESIGN/METHODOLOGY/APPROACH:
      The study draws on published work and applies its ideas to Chinese healthcare
      settings. Data consist of hospital service perceptions in the People's Republic
      of China (PRC), a society that is socially, economically and culturally
      undergoing major changes. In total, 96 patients were surveyed. Data relationships
      were tested using partial least square (PLS) analysis. FINDINGS: Findings show
      that Chinese patients' cultural values and their health service assessments are
      related and that the cultural values themselves seem to be changing.
      Additionally, further analyses provided interesting results pointing to which
      cultural values influenced service quality perceptions. The strongest service
      quality predictor was power distance. RESEARCH LIMITATIONS/IMPLICATIONS: The
      sample is relatively small and collected from only one major hospital in China.
      Therefore, future research should extend the sample size and scope. Follow-up
      research could also include cross-cultural investigations of perceived health
      service quality to substantiate cultural influences on health service quality
      perceptions. PRACTICAL IMPLICATIONS: In line with similar research in other
      contexts, the study confirms that power distance has a significant relationship
      with service quality perceptions. ORIGINALITY/VALUE: The study contributes to
      existing health service literature by offering patients' views on health service
      quality and by describing relationships between health service perceptions and
      cultural values--the study's main contribution.

PMID- 23534107
TI  - [All men are equal...but there are some more equal than others].

PMID- 23534108
TI  - [Is the coronary artery disease in woman so different from the man].
AB  - Clinical presentation and symptoms of coronary artery disease may vary according
      to gender. This is not true to the same extent for acute coronary syndromes. The
      diagnosis is more complex in women because they show less often a typical
      clinical picture. In spite of these gender-related clinical differences, no
      diagnostic strategy in the detection of the coronary artery disease is
      recommended for women. Because "standard" treadmill or bicycle ECG stress test
      has a low specificity in women, non-invasive imaging (stress echocardiography,
      myocardial scintigraphy or cardiac magnetic resonance) should be preferred for
      the evaluation of myocardial ischemia in women.

PMID- 23534109
TI  - [Cardiovascular cooperation with the BPKIHS Hospital, in Dharan Bazar, Nepal].
AB  - Thanks to a collaboration project that was developed by Swiss cardiologists, the
      Coeur de la Tour Foundation, and BPKIHS, a teaching hospital in Dharan, it has
      been possible, within two years and using a "hybrid approach", to set up the
      first independent invasive and interventional program in East Nepal. 496 patients
      have been investigated and/or treated since January 2011, during an initial
      period of 23 months (coronary angiographies, coronary angioplasties, temporary
      and permanent pacemaker implantations, pericardiocenteses, etc.). In parallel
      with this, our Foundation, in the same area of the country, has also supported a
      pre-existing cardiovascular prevention program and has helped start a population
      based study of rheumatic heart disease prevalence and treatment outcome among
      school children.

PMID- 23534110
TI  - [Hypertrophic cardiomyopathy in 2013].
AB  - Hypertrophic cardiomyopathy is the most common genetic heart disease. It is
      caused by a variety of mutations in genes encoding sarcomeric proteins. Clinical
      presentation is heterogeneous just as the clinical course, ranging from
      asymptomatic forms to sudden cardiac death in the young. The latter is an
      unpredictable, fortunately rather uncommon, complication with no reliable
      preventive treatment. The complexity lies in the identification of high risk
      patients who could benefit from an implantable cardioverter-defibrillator in
      primary prevention. Symptomatic patients presenting left ventricular outflow
      tract obstruction despite optimal medical treatment may undergo surgical septal
      myectomy or percutaneous alcohol septal ablation.

PMID- 23534112
TI  - [Endurance sports and arythmias].
AB  - Endurance sports can predispose to the occurrence of certain arrhythmias, making
      them more frequent in athletes than in the general population. Endurance athletes
      often exhibit electrocardiographic modifications that are difficult to interpret
      without specific knowledge of the athlete's ECG. Some of these ECG modifications
      and arrhythmias are benign, however others can be potentially life threatening.

PMID- 23534111
TI  - [Coronary artery disease: diagnostic approach in 2013].
AB  - Coronary disease can lead to very serious complications which sometimes may have
      dramatic consequences on the quality of life of our patients. In addition, it can
      also have numerous social repercussions including a significant increase in the
      health budget costs. Systematic evaluation adapted to each patient is crucial.
      Numerous diagnostic currently available tests when used in the appropriate manner
      can be of a precious help for the clinician and for the future of his patient.

PMID- 23534113
TI  - [Psychological aspects of the implantable cardioverter defibrillator: guidelines
      at the office].
AB  - Implantation of a defibrillator clearly extends life of heart patients. However,
      experience shows that this technique can also cause psychological difficulties,
      in some patients, making life sometimes unbearable. The risk of developing
      anxiety or depression is increased, causing a decrease in the quality of life.
      Feelings of helplessness, the unpredictability of the shock, are all factors that
      can cause psychological disturbances. An analysis of the risk factors is part of
      the evaluation of the clinician. We propose a practical guide, a series of simple
      questions to help discriminate patients to refer to a specialist.

PMID- 23534114
TI  - [Health system, discuss the prospects: dialoguing ].

PMID- 23534115
TI  - [Sets a good example!].

PMID- 23534116
TI  - [Epigenetics].

PMID- 23534117
TI  - [Kidney: transplantation is now an economic emergency].

PMID- 23534118
TI  - [Horse meat: first lessons of a scandal].

PMID- 23534119
TI  - [The latest diagnostics of Dr. House].

PMID- 23534120
TI  - [Liberty and plasticity].

PMID- 23534121
TI  - Clinical outcomes of transoral robotic surgery for head and neck tumors.
AB  - OBJECTIVES: In order to reduce treatment-related morbidity rates and increase
      patients' quality of life, robot-assisted surgery using the da Vinci surgical
      system (Intuitive Surgical Inc, Sunnyvale, California) has been studied actively
      in the field of head and neck surgery. This study analyzes our experiences
      therewith in order to evaluate the feasibility and efficacy of robot-assisted
      surgery via a transoral approach in the head and neck area. METHODS: Between
      April 2008 and December 2011, 141 patients were treated with robot-assisted
      surgery via a transoral approach. RESULTS: Robot-assisted surgeries were
      successfully completed via a transoral approach in all patients. The mean robotic
      operative time was 69.3 minutes, and the mean time for setup of the robotic
      system was 10.4 minutes. The average blood loss during the operation was 29.6 mL
      (range, 0 to 300 mL). Patients who underwent robot-assisted surgery were
      satisfied with their cosmetic results and treatment outcomes. CONCLUSIONS: Robot
      assisted surgery via a transoral approach was confirmed to be feasible and
      efficient in the field of head and neck surgery. Further research is needed to
      investigate the long-term functional and oncological results of robot-assisted
      surgery.

PMID- 23534122
TI  - Salvage transoral laser supraglottic laryngectomy after radiation failure: a
      report of seven cases.
AB  - OBJECTIVES: We evaluated the oncological and functional outcomes of salvage
      transoral laser supraglottic laryngectomy after radiation failure. In addition,
      we demonstrated the usefulness of laser surgery in patients with recurrent
      supraglottic cancer. METHODS: Between December 1999 and May 2011,7 patients (6
      men and 1 woman) underwent transoral laser supraglottic laryngectomy after
      radiation failure. We conducted 4 different types of endoscopic supraglottic
      laryngectomy. In the cases with lymph node metastasis, we performed neck
      dissection at the time of laser surgery. RESULTS: All patients had recurrent
      squamous cell carcinoma confirmed on the surgical specimen. Two patients were
      classified as having T1 disease, 2 as having T2 disease, and 3 as having T3
      disease with preepiglottic space involvement. The 2- and 5-year overall survival
      rates were 85.7% and 68.6%, respectively. There was a recurrence at 8 months of
      followup after laser surgery in 1 patient; he underwent successful salvage total
      laryngectomy. The ultimate local control rate was 100%, and the laryngeal
      preservation rate was 85.7%. The hospitalization times ranged from 2 to 32 days
      (mean, 15.6 days). The mean decannulation time was 10.7 days (range, 5 to 30
      days). All patients started oral feeding within 1 to 3 days after surgery.
      CONCLUSIONS: Salvage transoral laser supraglottic laryngectomy following
      radiation failure seems a feasible and oncologically safe procedure in recurrent
      supraglottic cancers ranging from T1 to selected T3 with minimal preepiglottic
      space involvement. It can be an option for minimally invasive organ preservation
      surgery with lesser morbidity for recurrent supraglottic cancer.

PMID- 23534123
TI  - Vestibular schwannoma in the only hearing ear: role of cochlear implants.
AB  - OBJECTIVES: We sought to delineate the role of cochlear implantation in the
      management of vestibular schwannoma or other cerebellopontine angle tumors in the
      only hearing ear. METHODS: We performed a retrospective analysis in a quaternary
      referral skull base center of all patients who were affected by vestibular
      schwannoma (or other lesions of the cerebellopontine angle) in the only hearing
      ear and received a cochlear implant before or after tumor treatment (surgery or
      radiotherapy) or during the wait-and-scan follow-up. We also performed a
      systematic review of the English-language literature. RESULTS: The clinical and
      audiological results of 10 patients are reported. All patients were managed with
      contralateral cochlear implantation. In 7 patients, cochlear implantation was
      performed before tumor removal, while hearing in the ear with the tumor was still
      present. In 3 patients, the implant was placed after curative surgery. Nine of
      the 10 patients routinely use their implant with subjective benefit and fairly
      good auditory performance (median disyllabic word recognition, 90%; median
      sentence comprehension, 75%). The literature search retrieved no major series
      with assessment of the long-term efficacy of cochlear implantation in this rare
      clinical scenario. CONCLUSIONS: Patients affected by vestibular schwannoma in
      their only hearing ear may significantly benefit from a cochlear implant on the
      contralateral side prior to tumor removal. Recent and significant hearing
      deterioration and tumor growth represent the main indications for cochlear
      implantation.

PMID- 23534125
TI  - Topographic distribution of biofilm-producing bacteria in adenoid subsites of
      children with chronic or recurrent middle ear infections.
AB  - OBJECTIVES: Bacterial biofilms have been found in the adenoids of children with
      recurrent acute otitis media (AOM) and persistent otitis media with effusion
      (OME). However, the possible difference in biofilm-producing bacteria (BPBs)
      between the adenoid surface at the nasopharyngeal dome (ND) and near the ostium
      of the eustachian tube (ET) has not been investigated. This study aimed to assess
      the difference in BPBs between adenoid biopsy specimens of the ND and those taken
      near the pharyngeal ostium of the ET in children with chronic adenoiditis with
      recurrent AOM and/or persistent OME. METHODS: We collected adenoid biopsy
      specimens from the ND and ET during transoral endoscopic adenoidectomy to assess
      BPB by means of spectrophotometric analysis. RESULTS: We collected 135 adenoid
      biopsy specimens from 45 children. BPBs were detected significantly (p = 0.04)
      more frequently in the ET samples than in the ND samples, mainly Staphylococcus
      aureus. Although the prevalence of S aureus was slightly greater in the ND
      samples, and that of Streptococcus pneumoniae and Moraxella catarrhalis was
      slightly greater in the ET samples, these differences were not statistically
      significant. CONCLUSIONS: The fact that BPBs were significantly more frequently
      located near the ostium of the ET suggests that the adenoids are a reservoir for
      bacteria and indicates that hypertrophic adenoids (particularly hypertrophy near
      the ostium of the ET) play a role in recurrent AOM and/or OME.

PMID- 23534124
TI  - Botulinum toxin injection for the treatment of upper esophageal sphincter
      dysfunction.
AB  - OBJECTIVES: We sought to review the dysphagia-related outcomes and quality of
      life in a series of patients with upper esophageal sphincter (UES) dysfunction
      treated with cricopharyngeal (CP) botulinum toxin (BTX) injection, and to
      identify patient characteristics or CP muscle histologic features that predict
      efficacy of BTX injection. METHODS: A retrospective chart review was performed on
      patients with UES dysfunction who underwent CP BTX injection. Dysphagia-related
      quality-of-life questionnaires based on the Eating Assessment Tool (EAT-10) were
      mailed to patients. RESULTS: Forty-nine patients (30 female, 19 male; average
      age, 59 +/- 16 years) with UES dysfunction have been treated at our institution
      with CP BTX injection since 2000. Seventeen of these patients also underwent CP
      myotomy. Injections of BTX were occasionally repeated after the treatment effect
      subsided, and the BTX dose varied widely (average, 39 +/- 19 units). Improvement
      in symptoms was noted by 65% of patients. The overall complication rate was
      minimal, although many patients complained of transient worsening of dysphagia
      after CP BTX injection. Biopsy specimens of the CP muscle were evaluated in the
      subset of patients with CP BTX injection who proceeded to myotomy, with results
      of neuropathic, myopathic, and mixed histologic subtypes. The EAT-10 scores
      demonstrated a general trend toward improved swallowing outcomes after CP BTX
      injection. CONCLUSIONS: This study reviewed findings from the largest published
      series of BTX treatment of UES dysfunction and evaluated the efficacy, patient
      satisfaction, and complications of this procedure. Dysphagia-related quality-of
      life outcomes appear to be improved after CP BTX injection.

PMID- 23534126
TI  - Dexmedetomidine versus morphine or fentanyl in the management of children after
      tonsillectomy and adenoidectomy: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: The primary objective of this review was to evaluate and compare the
      efficacy and safety of dexmedetomidine hydrochloride with the efficacy and safety
      of opioids for postoperative management of children after tonsillectomy and
      adenoidectomy. METHODS: We searched the Cochrane Central Register of Controlled
      Trials (Central) in the Cochrane Library (most recent issue), Medline (1966 to
      date) through Ovid, Embase (1980 to date), and Web of Science (1945 to date). The
      number of patients who required rescue analgesics (morphine or fentanyl) in the
      postanesthesia care unit, the number of patients with emergence agitation, the
      number of patients with postoperative nausea and vomiting, the time to eye
      opening in response to verbal stimuli, and the time to extubation were analyzed.
      RESULTS: We included 5 trials, consisting of 482 patients in total. There were no
      significant differences in the number of patients who required rescue analgesics
      in the postanesthesia care unit, the number of patients with emergence agitation,
      the number of patients with postoperative nausea and vomiting, or the time to
      extubation between patients who received dexmedetomidine and those who received
      opioids. Compared with opioids, dexmedetomidine was associated with a
      significantly decreased time to eye-opening in response to verbal stimuli (mean
      difference, -2.11 minutes; 95% confidence interval, -3.32 to -0.91 minutes; p =
      0.0006). CONCLUSIONS: Intraoperative use of dexmedetomidine was as effective as
      opioids in preventing postoperative pain and emergence agitation in children who
      had undergone tonsillectomy and adenoidectomy.

PMID- 23534127
TI  - Bone marrow-derived clonal mesenchymal stem cells as a source of cell therapy for
      promoting vocal fold wound healing.
AB  - OBJECTIVES: We investigated whether mouse bone marrow-derived clonal mesenchymal
      stem cells (BM-cMSCs) could promote vocal fold (VF) wound healing by using a
      xenograft animal model. METHODS: Homogeneous BM-cMSCs isolated by a
      subfractionation culturing method from the bone marrow aspirates of green
      fluorescent protein transgenic mice were injected into the VFs of rabbits
      immediately after direct mechanical injury. Macroscopic, biomechanical
      (rheometric), histologic, immunohistochemical, and transcriptional evaluations
      were performed on the scarred VFs 1 to 3 months after injury. Engraftment of the
      implanted BM-cMSCs was determined by detection of green fluorescent protein cells
      in the recipient VF by confocal microscopy. RESULTS: The BM-cMSC-treated VFs
      showed improved morphological properties and viscoelasticity as compared to
      control VFs injected with phosphate-buffered saline solution. Histologic and
      immunohistochemical evaluations showed less excessive collagen deposition and
      increased density of glycosaminoglycans in the BM-cMSC-treated VFs as compared to
      the control VFs at 3 months after injury (p = 0.003 and p = 0.037, respectively).
      BM-cMSC transplantation led to a significant attenuation of fibronectin (p =
      0.036) and transforming growth factor beta1 (p = 0.042) messenger RNA expression
      at 1 month after injury. Green fluorescent protein-expressing BM-cMSCs engrafted
      in recipient VFs were found at 1 month after implantation. CONCLUSIONS: BM-cMSCs
      appeared to survive in the injured xenogeneic VFs after transplantation for up to
      1 month and favorably enhanced the wound healing of VFs after injury. We conclude
      that BM-cMSCs are a possible source of cell therapy for vocal fold regeneration.

PMID- 23534128
TI  - Expression of autoantibodies in patients with sudden sensorineural hearing loss.
AB  - OBJECTIVES: The aim of this study was to establish the expression rate of
      autoimmunity in patients with sudden sensorineural hearing loss and to determine
      whether a positive marker is associated with a higher rate of hearing recovery
      after steroid treatment. METHODS: A prospective study was performed on 137
      patients who experienced sudden sensorineural hearing loss and underwent
      immunoserologic investigations. Autoantibodies evaluated on the day of admission
      included anti-double-stranded DNA, rheumatoid factor, antiphospholipid
      immunoglobulins G and M, antinuclear antibody, and complements C3 and C4.
      RESULTS: Of 137 patients, 75 were male and 62 were female (mean age, 45.1 years).
      Hearing loss was found on the left side in 61 patients and on the right side in
      76 patients. Elevation of at least 1 autoantibody or abnormal complement levels
      were found in 80 patients (58%), and abnormalities of 2 or more antibodies were
      found in 28 (20%). There were no statistically significant correlations between
      autoantibody abnormalities and age, initial hearing level, or positive treatment
      response. CONCLUSIONS: There is no clear evidence of a correlation between
      autoimmunity and hearing improvement in patients with autoantibody abnormalities.
      A high (but not significant) expression rate of autoantibody abnormality and
      complement level was seen in patients with sudden sensorineural hearing loss.

PMID- 23534129
TI  - Visualizing collagen network within human and rhesus monkey vocal folds using
      polarized light microscopy.
AB  - OBJECTIVES: Collagen fiber content and orientation affect the viscoelastic
      properties of the vocal folds, determining oscillation characteristics during
      speech and other vocalization. The investigation and reconstruction of the
      collagen network in vocal folds remains a challenge, because the collagen network
      requires at least micron-scale resolution. In this study, we used polarized light
      microscopy to investigate the distribution and alignment of collagen fibers
      within the vocal folds. METHODS: Data were collected in sections of human and
      rhesus monkey (Macaca mulatta) vocal folds cut at 3 different angles and stained
      with picrosirius red. RESULTS: Statistically significant differences were found
      between different section angles, implying that more than one section angle is
      required to capture the network's complexity. In the human vocal folds, the
      collagen fiber distribution continuously varied across the lamina propria (medial
      to lateral). Distinct differences in birefringence distribution were observed
      between the species. For the human vocal folds, high birefringence was observed
      near the thyroarytenoid muscle and near the epithelium. However, in the rhesus
      monkey vocal folds, high birefringence was observed near the epithelium, and
      lower birefringence was seen near the thyroarytenoid muscle. CONCLUSIONS: The
      differences between the collagen networks in human and rhesus monkey vocal folds
      provide a morphological basis for differences in viscoelastic properties between
      species.

PMID- 23534130
TI  - Putting pain on the front burner.

PMID- 23534131
TI  - NY hospital achieves TJC wound care certification.

PMID- 23534132
TI  - NQF, TJC honor Kaiser implant project.

PMID- 23534133
TI  - Cutting the volume of data down to size.

PMID- 23534134
TI  - Ensuring hand-washing when no one's watching.

PMID- 23534135
TI  - Upping the game for OR cleaning with monitoring and partnerships.

PMID- 23534136
TI  - Benchmarking labor productivity: how is your OR being compared?

PMID- 23534137
TI  - Simulation study supports use of crisis checklists.

PMID- 23534138
TI  - OR zone system: a fast and effective way to clean.

PMID- 23534139
TI  - Could technology lend a hand in cleaning of ORs?

PMID- 23534140
TI  - Safer surgery: the preoperative testing process.

PMID- 23534141
TI  - Why are there so many unneeded preop tests?

PMID- 23534142
TI  - Synergies are flowing from combined ST, CS role.

PMID- 23534143
TI  - Have you taken steps to avoid the abuse of IUSS?

PMID- 23534144
TI  - Health service performance and productivity.

PMID- 23534145
TI  - Increasing operating room productivity by duration categories and a newsvendor
      model.
AB  - PURPOSE: Previous studies approach surgery scheduling mainly from the
      mathematical modeling perspective which is often hard to apply in a practical
      environment. The aim of this study is to develop a practical scheduling system
      that considers the advantages of both surgery categorization and newsvendor model
      to surgery scheduling. DESIGN/METHODOLOGY/APPROACH: The research was carried out
      in a Finnish orthopaedic specialist centre that performs only joint replacement
      surgery. Four surgery categorization scenarios were defined and their
      productivity analyzed by simulation and newsvendor model. FINDINGS: Detailed
      analyses of surgery durations and the use of more accurate case categories and
      their combinations in scheduling improved OR productivity 11.3 percent when
      compared to the base case. Planning to have one OR team to work longer led to
      remarkable decrease in scheduling inefficiency. PRACTICAL IMPLICATIONS: In
      surgical services, productivity and cost-efficiency can be improved by utilizing
      historical data in case scheduling and by increasing flexibility in personnel
      management. ORIGINALITY/VALUE: The study increases the understanding of practical
      scheduling methods used to improve efficiency in surgical services.

PMID- 23534146
TI  - A study of complications affecting surgery performance: an ISM-based roadmap to
      patient flow.
AB  - PURPOSE: The aim of this study is to highlight the value of the success rate
      performance of a surgery while planning patient flow within a supply chain of a
      health care organization/hospital. DESIGN/METHODOLOGY/APPROACH: The paper has
      considered one of the common surgeries, cataract, and the complications that
      subsequently result from this surgery. The study employs interpretive structural
      modeling (ISM) approach to draw a roadmap to study various complications causing
      cataract that subsequently help in planning and coordination of patient flow.
      FINDINGS: The study finds that there is a hierarchy of causes and certain
      complications, the persistence of which gives a higher success rate performance
      in cataract surgery as compared to others. PRACTICAL IMPLICATIONS: The paper
      provides leverage to the decision maker while organizing the patient flow
      depending upon the information of hierarchy of complication of a disease, and
      accordingly ensures the availability of resources to the patient.
      ORIGINALITY/VALUE: The study is of value in identifying the degree of
      complications from cataract surgery. Given the degree of complication, the
      patient logistics can be planned myopically in a health care organization which
      largely depends upon the degree of success rate. The paper attempts to suggest
      that the hierarchy obtained through ISM can be implemented in the modules of an
      enterprise resource planning (ERP) set up.

PMID- 23534147
TI  - A comparison of two diagnostic performance measures: signal-to-noise ratio versus
      partial area under receiver operating characteristic curve.
AB  - PURPOSE: This paper aims to compare two diagnostic performance measures, i.e.
      signal-to-noise ratio (S/N ratio) and partial area under receiver operating
      characteristic curves (pAUC). It proposes the use of S/N ratio rather than pAUC
      for establishing optimal cut-off point for diagnostic biomarkers.
      DESIGN/METHODOLOGY/APPROACH: This paper discusses the properties, uses,
      advantages and shortcomings of the two performance measures, namely the partial
      area under receiver operating characteristic curve (pAUC) and Taguchi's signal-to
      noise (S/N) ratio. The benefits of S/N ratio have been illustrated in a sample of
      four biomarkers, each having five cut-off points. The S/N ratio is compared to
      the pAUC index. The SAS software is employed to calculate pAUC and AUC. FINDINGS:
      This paper shows that S/N ratio can be used as a measure of diagnostic accuracy.
      The cut-off point with the highest S/N ratio is the optimal cut-off point for the
      biomarker. The proposed method has the advantages of being easier, more practical
      and less costly than that of pAUC. PRACTICAL IMPLICATIONS: This paper includes
      implications for the development of a more practical, equally powerful and less
      costly means of measuring clinical accuracy thereby reducing the costs and risks
      resulting from wrong selection of cut-off point can be decreased.
      ORIGINALITY/VALUE: This paper supports suggestions in the recent literature to
      replace pAUC with a new, more meaningful index.

PMID- 23534148
TI  - Reducing hospital associated infection: a role for social marketing.
AB  - PURPOSE: Although hand hygiene is seen as the most important method to prevent
      the transmission of hospital associated infection in the UK, hand hygiene
      compliance rates appear to remain poor. This research aims to assess the degree
      to which social marketing methodology can be adopted by a particular organisation
      to promote hand hygiene compliance. DESIGN/METHODOLOGY/APPROACH: The research
      design is based on a conceptual framework developed from analysis of social
      marketing literature. Data collection involved taped interviews given by nursing
      staff working within a specific Hospital Directorate in Manchester, England.
      Supplementary data were obtained from archival records of the hand hygiene
      compliance rates. FINDINGS: Findings highlighted gaps in the Directorate's
      approach to the promotion of hand hygiene compared to what could be using social
      marketing methodology. Respondents highlighted how the Directorate failed to
      fully optimise resources required to endorse hand hygiene practice and this
      resulted in poorer compliance. PRACTICAL IMPLICATIONS: From the experiences and
      events documented, the study suggests how the emergent phenomena could be
      utilised by the Directorate to apply a social marketing approach which could
      positively influence hand hygiene compliance. ORIGINALITY/VALUE: The paper seeks
      to explore the use of social marketing in nursing to promote hand hygiene
      compliance and offer a conceptual framework that provides a way of measuring the
      strength of the impact that social marketing methodology could have.

PMID- 23534149
TI  - Quality function deployment in healthcare: a literature review and case study.
AB  - PURPOSE: This article aims to provide a literature review on the use of quality
      function deployment (QFD) in healthcare and a case study in order to provide
      contextual knowledge as a means of improving applications of QFD in healthcare.
      DESIGN/METHODOLOGY/APPROACH: The literature search was done via Google Scholar,
      PubMed/MEDLINE, and Web of Science using the keywords "quality function
      deployment" and "healthcare"; focusing on journal publications and their related
      citations. The case study was done within a design for Six Sigma project (DFSS)
      in a Swedish hospital. Empirical data were collected through face-to-face
      interviews and project documentation. FINDINGS: Four potentials (better
      understanding of customers' needs and wants, identification of opportunities for
      process improvement, effective system thinking approach, and better communication
      and more transparent process) and three antecedents (understanding the customer,
      understanding the customer's needs, and finding ways to prioritize and translate
      those needs) of QFD application in healthcare were identified from the literature
      review. From the case study, the application of QFD leads to an increased
      awareness of a complex multiple-customer concept, traceability of the improvement
      strategies in a more structured way, and the formation of a new process
      organization. A time study at one clinic (cardiology) before and after the
      project within which the QFD was used showed that the time spent on prescription
      of medication has decreased by more than 20 percent. This has increased the time
      that doctors can spend with their patients. PRACTICAL IMPLICATIONS: This paper
      highlights the potentials and antecedents of applying QFD in healthcare from
      previous research. Furthermore, the practical findings obtained from applying QFD
      in the project can also provide some useful insights for practitioners.
      ORIGINALITY/VALUE: The novel contribution is two-fold. First, it is the
      identification of the potentials and antecedents of using QFD in healthcare
      context. Second, it is the findings and learning from a practical application of
      QFD for improving a medication process in the hospital.

PMID- 23534150
TI  - Obstacles to TQM success in health care systems.
AB  - PURPOSE: Many healthcare organisations have found it difficult to implement total
      quality management (TQM) successfully. The aim of this paper is to explore the
      barriers to TQM successful implementation in the healthcare sector.
      DESIGN/METHODOLOGY/APPROACH: This paper reports a literature review exploring the
      major reasons for the failure of TQM programmes in healthcare organisations.
      FINDINGS: TQM implementation and its impact depend heavily on the ability of
      managers to adopt and adapt its values and concepts in professional healthcare
      organisations. Unsuccessful TQM efforts in healthcare organisations can be
      attributed to the strongly departmentalised, bureaucratic and hierarchical
      structure, professional autonomy, tensions between managers and professionals and
      the difficulties involved in evaluating healthcare processes and outcomes. Other
      obstacles to TQM success include lack of consistent managers' and employees'
      commitment to and involvement in TQM implementation, poor leadership and
      management, lack of a quality-oriented culture, insufficient training, and
      inadequate resources. The review was limited to empirical articles written in the
      English language during the past 30 years (1980-2010). PRACTICAL IMPLICATIONS:
      The findings of this article provide policy makers and managers with a practical
      understanding of the factors that are likely to obstruct TQM implementation in
      the healthcare sector. ORIGINALITY/VALUE: Understanding the factors that obstruct
      TQM implementation would enable managers to develop more effective strategies for
      implementing TQM successfully in healthcare organisations.

PMID- 23534151
TI  - Simulation team training for improved teamwork in an intensive care unit.
AB  - PURPOSE: This study aims to describe implementation of simulator-based medical
      team training and the effect of this programme on inter-professional working in
      an intensive care unit (ICU). DESIGN/METHODOLOGY/APPROACH: Over a period of two
      years, 90 percent (n = 152) of the staff of the general ICU at Karolinska
      University Hospital, Huddinge, Sweden, received inter-professional team training
      in a fully equipped patient room in their own workplace. A case study method was
      used to describe and explain the planning, formation, and results of the training
      programme. FINDINGS: In interviews, the participants reported that the training
      had increased their awareness of the importance of effective communication for
      patient safety. The intervention had even had an indirect impact by creating a
      need to talk, not only about how to communicate efficaciously, but also
      concerning difficult care situations in general. This, in turn, had led to
      regular reflection meetings for nurses held three times a week. Examples of
      better communication in acute situations were also reported. However, the
      findings indicate that the observed improvements will not last, unless
      organisational features such as staffing rotas and scheduling of rounds and
      meetings can be changed to enable use of the learned behaviours in everyday work.
      Other threats to sustainability include shortage of staff, overtime for staff,
      demands for hospital beds, budget cuts, and poor staff communication due to
      separate meetings for nurses and physicians. ORIGINALITY/VALUE: The present
      results broaden our understanding of how to create and sustain an organizational
      system that supports medical team training.

PMID- 23534152
TI  - [The human at the center].

PMID- 23534153
TI  - [Symptom management: a nursing theory and its application. The experience of the
      patient as the focus].

PMID- 23534154
TI  - [The legal aspects of wound treatment].

PMID- 23534155
TI  - [Sister Liliane Juchli. The light house is of no use when the fire isn't
      burning].

PMID- 23534156
TI  - [Patient education. Micro-education about oral anticoagulation].

PMID- 23534157
TI  - [Advanced practice nursing in the German language area. Nursing expert advanced
      practice nurse defined].

PMID- 23534158
TI  - [Dying, death and funeral. Making room for Muslim rituals].

PMID- 23534159
TI  - [Risk of decubitus ulcer and therapy. Measuring movement more objectively].

PMID- 23534160
TI  - [Elderly patients in the acute hospital. Discrimination that is hardly
      noticeable].

PMID- 23534161
TI  - [Dealing with manipulations of the arm of patients after axillary lymph node
      excision. Preventing the risk of lymphedema].

PMID- 23534162
TI  - [Everything for the patient].

PMID- 23534163
TI  - [Esthetic care for elderly hospitalized patients. Balm for the morale].

PMID- 23534164
TI  - [Reflective practice. A journal club for nurse clinicians].

PMID- 23534165
TI  - [Starting out in the profession. Feeling indignant and after...].

PMID- 23534166
TI  - [The forgivable and unforgivable. Secrets of tears].

PMID- 23534167
TI  - [Who could be a better doctor of himself?].

PMID- 23534168
TI  - [Shiatsu].

PMID- 23534169
TI  - New pastures pose new challenges.

PMID- 23534170
TI  - Effect of progressive muscle relaxation versus intake of ginger powder on
      dysmenorrhoea amongst the nursing students in Pune.
AB  - The present study was conducted to examine the comparative efficacy of
      progressive muscle relaxation and the oral intake of ginger on symptoms of
      dysmenorrhoea among nursing students of Pune, Maharashtra. The study students (n
      = 75) were divided into three groups, two experimental and one control Ginger
      powder 1 gm per dose was administered twice a day with warm water after meal to
      the second experimental group during the first three days of their menstruation.
      Main outcome measures were the severity of selected symptoms of dysmenorrhoea.
      The daily symptom calendar, a 5-point Likert Scale was used to assess the
      severity of selected symptoms of dysmenorrhoea. Main outcome measures were the
      severity of selected symptoms of dysmenorrhoea, which were analysed using MANOVA.
      It was concluded that in treating symptoms of dysmenorrhoea, ginger powder has
      efficacy superior to progressive muscle relaxation.

PMID- 23534171
TI  - Knowledge of adolescent girls regarding reproductive health care.
AB  - The period of adolescence (usually 15-19 years) is marked by physiological
      changes in the body, more so with females. Unfortunately sex and sex education
      continue to be taboo. A study was therefore conducted among adolescent girls of
      urban slum area of Niladribihar, Khurda district of Odisha. The sample consisted
      of 84 adolescent girls. The analysis showed that adolescent girls had average
      reproductive health care that can lead to numerous health problems and there is
      dire need of evolving measures to improve their knowledge on reproductive health
      care. Nursing professionals in hospital setting can significantly contribute in
      this area.

PMID- 23534172
TI  - Impact of health education on the knowledge of tuberculosis among sputum-positive
      pulmonary TB patients and their care-givers.
AB  - Tuberculosis is a world-wide disease, the chest affliction (pulmonary
      tuberculosis) being the commonest. Over 14 million persons are estimated to
      presently suffer from acute tuberculosis. Poverty apart, ignorance about origin,
      spread and prevention is a major factor in the large scale prevalence of the
      disease. It was therefore decided to assess the impact of health education among
      sputum-positive pulmonary tuberculosis patients and their caregivers on all
      aspects and also to evaluate their knowledge on day of allocation of treatment.
      Using a structured questionnaire with multiple choices regarding signs &
      symptoms, causes, transmission of tuberculosis, availability of treatment etc. on
      56 patients and 62 care-givers. The study concludes that direct and indirect
      methods of health education significantly enhance the awareness about the nature,
      spread and prevention of tuberculosis.

PMID- 23534173
TI  - Mind - body connection.

PMID- 23534174
TI  - Address by Dr A PJ Abdul Kalam, former president of India.

PMID- 23534175
TI  - Presidential address by Prof (Sr) Gilbert, President, TNAI.

PMID- 23534176
TI  - Nurse's role in assisting psychosocial recovery during acute phase of disasters.

PMID- 23534177
TI  - Effect of distraction techniques in behaviour responses to pain among toddlers
      receiving immunisation.
AB  - Pain and distress during immunisation of toddlers are reasons for non
      immunisation of large number of toddlers. The present study was undertaken to
      assess the comparative effectiveness of distraction techniques in the process of
      immunisation i.e. toy and music. (The third group of study subjects was control
      group). It is concluded that distraction techniques are quite economical and safe
      in enhancing the magnitude of immunisation.

PMID- 23534178
TI  - Problems faced and coping strategies used by adolescents with mentally ill
      parents in Delhi.
AB  - The present study was conducted to assess the problems faced by adolescents whose
      parents suffer from major mental illness at selected mental health institutes of
      Delhi. The objectives also included assessment of the coping strategies of the
      adolescents in dealing with these problems. The Stuart Stress Adaptation Model of
      Psychiatric Nursing Care was used as the conceptual framework. A descriptive
      survey approach with cross-sectional design was used in the study. A structured
      interview schedule was prepared. Purposive non-probability sampling technique was
      employed to interview 50 adolescents whose parents suffer from major mental
      illness. Data gathered was analysed and interpreted using both descriptive and
      inferential statistics. The study showed that majority of the adolescents had
      moderate problems as a result of their parent's mental illness. Area-wise
      analysis of the problems revealed that the highest problems faced were in family
      relationship and support and majority of the adolescents used maladaptive coping
      strategies. A set of guidelines on effective coping strategies was disseminated
      to these adolescents.

PMID- 23534179
TI  - Effect of psycho-educative intervention on knowledge about illness and self-care
      in patients with schizophrenia.
AB  - In view of growing incidences of schizophrenia, a common mental disorder, present
      study enrolled 60 such patients (30 each in experimental and control groups) to
      evaluate pre- and post-intervention knowledge of schizophrenic patients and their
      self-care performance among in-patients of LGB Regional Institute of Mental
      Health in Tejpur (Assam). An association between knowledge and self-care
      performance was also studied. The findings revealed deficiencies in self-care
      performance and areas of knowledge among schizophrenic patients. However, the
      psycho-education intervention was effective on both the counts.

PMID- 23534180
TI  - Assessing the attitudes and perceptions towards nursing profession among nursing
      students.
AB  - Nursing education is a challenge in a developing country like India. This cross
      sectional study assessed the attitudes and perceptions of nursing professionals
      and their desired future practices. The study was conducted using a modified
      version of Beliefs, Attitudes and Perceived Practice questionnaire among 129
      students who were undergoing undergraduate nursing programme at a selected
      college of nursing in Bangalore. Data was analysed and interpreted by using
      descriptive and inferential statistics. Forty-four (34.1%) of the subjects agreed
      that they were enrolled of their own interest; 43 (33.3%) of them reported that
      they enrolled in nursing out of their own interest and also to improve their
      financial situations. Only 4 (3.1%) stated that they have to protect the rights
      and dignity of the patients. 45 (34.9%) of the subjects indicated that the nurse
      patient relationship should be both professional and a relation of sympathy. Upon
      graduation 69 (53.5%) of the subjects preferred to pursue the nursing career, 36
      (27.9%) in academics, 12 (9.30%) wanted to change the profession. Nearly 63
      (48.8%) of the subjects agreed that social prejudice has a great influence on
      nursing students in choosing nursing profession as their career. An urgent need
      is seen in the area of educating nursing students regarding patient's rights.
      There is also a need to improve the image of nurses in the society to attract
      more number of students into this noble profession. Counselling and introduction
      to nursing course should be introduced by all the universities, to develop
      positive attitudes towards nursing profession.

PMID- 23534181
TI  - Concepts and characteristics of nursing leadership.

PMID- 23534182
TI  - A salute to an exemplary and divine nursing.

PMID- 23534183
TI  - Neonatal sepsis, bacterial isolates and antibiotic susceptibility patterns among
      neonates.
AB  - Data from hospital records of 96 neonates hospitalised with sepsis were analysed
      using SPSS 11.5 version to identify sepsis--its signs and symptoms with which
      they were admitted, bacterial isolates and antibiotic susceptibility patterns
      among neonates admitted during 2007-2009. The retrospective data revealed that
      majority of the neonates 61 (63.5%) were males. Of the 96 neonates 52 (54.2%)
      were pre-term, and 44 (45.8%) were referred from various institutes after initial
      trial of management for the same. Majority ie. 66 (68.8%) had respiratory
      distress. Lethargy was noted in 56 (58.30%), fever among 10 (10.4%) and jaundice
      was reported among 6 (6.2%). Blood culture and sensitivity revealed that
      pseudomonas infection claimed to have triggered early signs and symptoms of
      sepsis among 11 (11.46%) neonates and Staphylococcus aureus was responsible for
      triggering late signs and symptoms ofsep is among 11 (11.46%) neonates.

PMID- 23534184
TI  - Presidential address by Prof (Sr) Gilbert at the XXIV SNA Biennial Conference at
      Bengaluru on 27 November 2011.

PMID- 23534185
TI  - Unfolding the theme: preparation of nursing students for leadership role.

PMID- 23534186
TI  - Scientific paper presentation: Plenary Session-I. Sub theme: impact of social
      change on nursing education.

PMID- 23534187
TI  - Scientific paper presentation: plenary session-I. Sub theme: impact of social
      change on nursing education. Assessing the vulnerable stress level and coping
      mechanism of residential and day scholars of a nursing college.

PMID- 23534188
TI  - Scientific paper presentation: plenary session-II. Sub theme: challenges before
      nursing students in health care delivery.

PMID- 23534189
TI  - Scientific paper presentation: plenary session-II. Sub theme: challenges before
      nursing students in health care delivery. Assessment of knowledge and attitude on
      leadership among nursing students.

PMID- 23534190
TI  - Scientific paper presentation: plenary session-III. Sub theme: information
      technology and nursing education. Effect of classroom demonstration and video
      demonstration on knowledge and practice among nursing students.

PMID- 23534191
TI  - Assessment of the attitude of staff nurses towards hospitalised psychiatric
      patients in Kolar (Karnataka).
AB  - As in other fields, the awareness of patients regarding their rights in seeking
      right or opting for particular modality of treatment is on the increase. This
      study sought to assess the attitude of staff nurses towards psychiatric patients
      hospitalised in a hospital in Karnataka. The study included 15 Diploma and as
      many Degree level nursing students. Using convenience sampling technique, authors
      conclude that graduate nurses were more articulate in asserting that hospitalised
      psychiatric patients were justified in seeking information about their illness
      and treatment or declining treatment than diploma students. The authors also
      suggest in-service education programme for nurses so as to inculcate a more
      positive attitude towards mentally ill patients.

PMID- 23534192
TI  - Children's representation of long duration: when memory and attention meet in
      processing time.
AB  - The concepts of the memory and attentional models were examined in children's and
      adults' time perception in a long duration. One hundred twenty-one children in
      preschool through Grade 2 and 29 adults for Study 1 and 93 second-, fourth-, and
      sixth-grade students and 40 adults for Study 2 judged durations of tasks that
      varied in interest levels and cognitive demands. In Study 1, children
      overestimated but adults underestimated the movie that they found to be
      interesting. However, in Study 2, both children and adults consistently
      overestimated the duration of puzzles they found to be interesting. In a long
      duration, the findings were more in line with the memory model than with the
      attention model. A qualitative change also emerged in middle childhood in the way
      children kept track of time; this difference may influence the developing
      perception of long duration in children's representation. Implications of the
      findings are further discussed in examining the perception of long duration.

PMID- 23534193
TI  - The mediating role of interpersonal cognition on the relationships between
      personality and adolescent ego development.
AB  - The author investigated whether interpersonal cognition mediated the
      relationships between defense, social sensitivity, and ego development.
      Participants (N = 616; M age = 15.66 years, SD = .52 year; 276 boys) from
      northwestern Taiwan completed a battery of questionnaires. Structural equation
      modeling and mediation analyses supported the hypothesis that interpersonal
      cognition would mediate the path between defense and ego development, and the
      path between social sensitivity and ego development. Defense and social
      sensitivity were found to have direct effects on ego development. The study
      provides evidence of the mediating effect of interpersonal cognition on the
      association between personality and ego development.

PMID- 23534194
TI  - The modified Brown-Peterson task: a tool to directly compare children and adult's
      working memory.
AB  - The study had 2 major purposes. First, it showed that the same task (Brown
      Peterson task) can be used to test the memory abilities of both young children
      and adults, given an appropriate distracter task. Second, it illustrated that
      children can perform as accurately as adults on working memory tasks when
      prompted to use memory techniques such as rehearsal. Specifically, a modified
      version of the Brown-Peterson task (typically used with adults), tested working
      memory of adults and children aged 5-6 years. The modification was reciting the
      pledge of allegiance as the distracter task, as the pledge is at a level where
      young children are just learning it, and thus they know it, but not exceptionally
      well. Adults would have previously overlearned it as children but may not have
      recited it recently. This allows for the use of the same distracter task, thus
      allowing for a direct comparison of children and adults. Under experimental
      conditions, both groups showed a typical Brown-Peterson decay curve, with
      children showing a steeper decay than adults. With no distracter, adults
      performed at ceiling level, but only when rehearsal was encouraged did the
      accuracy of recalling the trigrams in the Brown-Peterson task improve for
      children, resulting in similar performance as adults.

PMID- 23534195
TI  - Theory of mind understanding and conversational patterns in middle childhood.
AB  - The author investigated the longitudinal relations between theory of mind (ToM)
      understanding and perceptions of self and social conversations in 17 school-aged
      children (12 girls, 5 boys, age 8-12 years). ToM was assessed at Time 1 (T1; M
      age = 8 years 5 months, SD = 8.7 months, and perceptions of self and
      conversational experiences assessed two years later at Time 2 (T2; M age = 10
      years 4 months, SD = 7.9 months. Most importantly, longitudinal findings showed
      that children who scored relatively high on ToM at T1 reported relatively lower
      perceptions of self-worth and higher number of mental states verbs in their
      perceptions of peer and family conversations at T2. Significant negative
      longitudinal associations were found between children's number of siblings and
      their perceptions of self-worth (T1) and number of cognitive terms in their
      perceptions of peer and family conversations (T2). Frequency analysis suggested
      that girls' perceptions of conversations referred to more social and
      psychological aspects of self and relationships, whereas boys focused mainly on
      physical activities. Most children were more likely to prefer listening to
      talking during social conversations. The majority of children reported feelings
      of mixed or ambiguous emotions during experiences of silence. Implications for
      socioemotional and cognitive development in early adolescents are discussed.

PMID- 23534196
TI  - Gender differences in preschool children's commentary on self and other.
AB  - To examine gender differences in commentary about self and others in same- and
      mixed-gender contexts, the authors analyzed dyadic conversations involving 78
      children in 5 preschool facilities. Compared to girls talking to girls, boy
      talking to boys made more statements with negative connotations for others and
      less often pointed out self-other similarities. No gender differences were
      observed in mixed-gender contexts. Compared to boys talking with boys, boys
      talking with girls spoke more frequently of similarities and abilities. Compared
      to girls with girls, girls with boys less often spoke descriptively or talked of
      activities and possessions and more often spoke of conduct, possibly in an effort
      to manage boys' behavior. Overall, the findings support a social-constructivist
      or contextual rather than a biological perspective on early gender differences.

PMID- 23534197
TI  - Adolescents' reasoning about parental gender roles.
AB  - In an examination of how adolescents reason about several factors related to
      division of childcare labor, 38 adolescents, including 20 girls (M age = 16.36
      years, SD = .50) and 18 boys (M age = 16.59 years, SD = .62) were interviewed
      about conflicts between a mother and a father over which parent should stay home
      with the child, the authority of the father, and similar issues in a traditional
      culture. The relative income of each parent was varied. Participants considered
      the needs of the child most when reasoning about infants, and the right to work
      most frequently when reasoning about preschoolers (p < .001, eta2 = .35). The
      majority (71%) did not endorse the husband's authority over the wife. However,
      boys were more likely than girls to emphasize the mother's responsibility to the
      child over her right to work (p < .01, eta2 = .23). Implications for gender
      equity and adolescents' future goals were discussed.

PMID- 23534198
TI  - Influence and mechanism of N-(3-oxooxtanoyl)-L-homoserine lactone (C8-oxo-HSL) on
      biofilm behaviors at early stage.
AB  - N-acyl-homoserines quenching, enzymatic quenching of bacterial quorum sensing,
      has recently applied to mitigate biofilm in membrane bioreactor. However, the
      effect of AHLs on the behavior of biofilm formation is still sparse. In this
      study, Pseudomonas aeruginosa biofilm was formed on ultra-filtration membrane
      under a series of N-(3-oxooxtanoyl)-L-homoserine lactone (Cs-oxo-HSL)
      concentrations. Diffusing C8-oxo-HSL increased the growth rate of cells on
      biofilm where the concentration of C8-oxo-HSL was over 10(-7) g/L. The C8-oxo-HSL
      gradient had no observable influence on cell density and extracellular polymeric
      substances of biofilm with over 10(-7) g/L C8-oxo-HSL. Surprisingly, 10(-11)-10(
      8) g/L of C8-oxo-HSL had no effect on cell growth in liquid culture. The cell
      analysis demonstrated that the quorum sensing system might enhance the growth of
      neighboring cells in contact with surfaces into biofilm and may influence the
      structure and organization of biofilm.

PMID- 23534199
TI  - Metals in sediment/pore water in Chaohu Lake: distribution, trends and flux.
AB  - Nine metals, Cd, Cu, Ni, Pb, As, Cr, Zn, Fe, and Mn in sediment and pore water
      from 57 sampling sites in Chaohu Lake (Anhui Province, China) were analyzed for
      spatial distribution, temporal trends and diffuse flux in 2010. Metals in the
      surface sediment were generally the highest in the western lake center and Nanfei
      Dianbu River estuary, with another higher area of As, Fe, and Mn occurring in the
      Qiyang River estuary. Metal contamination assessment using the New York sediment
      screening criteria showed that the sediment was severely contaminated in 44% of
      the area with Mn, 20% with Zn, 16% with Fe, 14% with As, and 6% with Cr and Ni.
      An increasing trend of toxic metals (Cd, Cu, Ni, Pb, As, Cr, Zn) and Mn with
      depth was shown in the western lake. Compared with metal content data from the
      sediment survey conducted in 1980s, the metal content of surface sediment in 2010
      was 2.0 times that in the 1980s for Cr, Cu, Zn, and As in the western lake, and
      less than 1.5 times higher for most of the metals in the eastern lake. Among the
      metals, only Mn and As had a widespread positive diffuse flux from the pore water
      to overlying water across the whole lake. The estimated flux in the whole lake
      was on average 3.36 mg/(m2 x day) for Mn and 0.08 mg/(m2 x day) for As, which
      indicated a daily increase of 0.93 microg/L for Mn and 0.02 microg/L for As in
      surface water. The increasing concentration of metals in the sediment and the
      flux of metals from pore water to overlying water by diffusion and other physical
      processes should not be ignored for drinking-water sources.

PMID- 23534200
TI  - Distribution of heavy metals in the water column, suspended particulate matters
      and the sediment under hydrodynamic conditions using an annular flume.
AB  - Sediment resuspension plays an important role in the transport and fate of heavy
      metals in the aquatic environment. In the present study, the release and binding
      forms of Cr, Cu, Zn, Pb under hydrodynamic conditions were investigated using an
      annular flume. Two sediments located at YLZ and GBD from Liangshui River, Beijing
      were resuspended for 10 hr at 0.159 and 0.267 m/sec, respectively. The
      concentrations of suspended particulate matters of YLZ were higher than those of
      GBD during resuspension, indicating that the former sediment is more sensitive to
      the velocity. Cr in the dissolved phase stayed nearly constant at about 2.25 and
      1.84 micro/L for YLZ and GBD, respectively, due to the high percentage of its
      stable binding fractions in both sediments, while Cu, Zn, and Pb showed a fast
      release in the initial period of time. However, their concentrations in SPM
      generally decreased with time and were higher at the lower velocity of 0.159
      m/sec, which resulted from the entrainment and depressing effect of larger size
      particles with lower heavy metal content, commonly referred to as the "particle
      concentration effect". In addition, the binding form and heavy metal fractions
      were also found to vary during the resuspension event. A decrease in the
      sulphide/organic matters bounded form in GBD sediment was observed, whereas no
      visible changes were perceived in YLZ site samples. This phenomenon is due to the
      oxidation of heavy metal-sulphide binding forms, which originated from its high
      acid volatile sulphide content in GBD sediment.

PMID- 23534202
TI  - Spectroscopic studies of dye-surfactant interactions with the co-existence of
      heavy metal ions for foam fractionation.
AB  - The interaction between a cationic dye Methylene Blue (MB) and an anionic
      surfactant sodium dodecyl sulfate (SDS) with the presence of Cd2+ was
      investigated spectrophotometrically in a certain concentration range. The
      spectrophotometric measurements of dye-metal ion-surfactant system were carried
      out. The results indicated that the SDS concentration had a significant influence
      on the dye spectrum, while the addition of Cd2+ hardly caused change of the
      maximum value of absorbance. According to this observation, we concluded that
      electrostatic and hydrophobic interaction between dye and surfactant occurred up
      to a certain level, and the homo-ions Cd2+ almost exerted no effect on the dye
      surfactant complexation, establishing a theoretical foundation for simultaneous
      removal of organic dye and heavy metal using foam fractionation. Meanwhile, the
      effects of their interaction on foam performance were investigated. The results
      showed that the addition of Cd2+ favored the tendency to ameliorate foam
      properties just contrary to MB. The feasibility of foam separation for dye and
      heavy metal removal from simulated wastewater was also confirmed using a
      continuous foam fractionator. In the simultaneous removal process, with the
      initial SDS concentration ranging from 0.5 to 5.0 mmol/L, the maximum removal
      efficiencies of MB and Cd2+ were obtained as 99.69% and 99.61%, respectively. The
      enrichment ratios were reduced from 24.34 to 7.65 for MB and from 22.01 to 3.35
      for Cd2+.

PMID- 23534201
TI  - Optimization of H2O2 dosage in microwave-H2O2 process for sludge pretreatment
      with uniform design method.
AB  - A microwave-H2O2 process for sludge pretreatment exhibited high efficiencies of
      releasing organics, nitrogen, and phosphorus, but large quantities of H2O2
      residues were detected. A uniform design method was thus employed in this study
      to further optimize H2O2 dosage by investigating effects of pH and H2O2 dosage on
      the amount of H2O2 residue and releases of organics, nitrogen, and phosphorus. A
      regression model was established with pH and H2O2 dosage as the independent
      variables, and H2O2 residue and releases of organics, nitrogen, and phosphorus as
      the dependent variables. In the optimized microwave-H2O2 process, the pH value of
      the sludge was firstly adjusted to 11.0, then the sludge was heated to 80 degrees
      C and H2O2 was dosed at a H2O2:mixed liquor suspended solids (MLSS) ratio of 0.2,
      and the sludge was finally heated to 100 degrees C by microwave irradiation.
      Compared to the microwave-H2O2 process without optimization, the H2O2 dosage and
      the utilization rate of H2O2 in the optimized microwave-H2O2 process were reduced
      by 80% and greatly improved by 3.87 times, respectively, when the H2O2:MLSS
      dosage ratio was decreased from 1.0 to 0.2, resulting in nearly the same release
      rate of soluble chemical oxygen demand in the microwave-H2O2 process without
      optimization at H2O2:MLSS ratio of 0.5.

PMID- 23534203
TI  - A VUV photoionization mass spectrometric study on the OH-initiated photooxidation
      of isoprene with synchrotron radiation.
AB  - The gas-phase organic compounds resulting from OH-initiated photooxidation of
      isoprene have been investigated on-line by VUV photoionization mass spectrometry
      based on synchrotron radiation for the first time. The photoionization efficiency
      curves of the corresponding gaseous products as well as the chosen standards have
      been deduced by gating the interested peaks in the photoionization mass spectra
      while scanning the photon energy simultaneously, which permits the identification
      of the pivotal gaseous products of the photooxidation of isoprene, such as
      formaldehyde (10.84 eV), formic acid (11.38 eV), acetone (9.68 eV), glyoxal (9.84
      eV), acetic acid (10.75 eV), methacrolein (9.91 eV), and methyl vinyl ketone
      (9.66 eV). Proposed reaction mechanisms leading to the formation of these key
      products were discussed, which were completely consistent with the previous works
      of different groups. The capability of synchrotron radiation photoionization mass
      spectrometry to directly identify the chemical composition of the gaseous
      products in a simulation chamber has been demonstrated, and its potential
      application in related studies of atmospheric oxidation of ambient volatile
      organic compounds is anticipated.

PMID- 23534204
TI  - Mercury oxidation and adsorption characteristics of potassium permanganate
      modified lignite semi-coke.
AB  - The adsorption characteristics of virgin and potassium permanganate modified
      lignite semi-coke (SC) for gaseous Hg0 were investigated in an attempt to produce
      more effective and lower price adsorbents for the control of elemental mercury
      emission. Brunauer-Emmett-Teller (BET) measurements, X-ray powder diffraction
      (XRD) and X-ray photoelectron spectroscopy (XPS) were used to analyze the surface
      physical and chemical properties of SC, Mn-SC and Mn-H-SC before and after
      mercury adsorption. The results indicated that potassium permanganate
      modification had significant influence on the properties of semi-coke, such as
      the specific surface area, pore structure and surface chemical functional groups.
      The mercury adsorption efficiency of modified semi-coke was lower than that of SC
      at low temperature, but much higher at high temperature. Amorphous Mn7+, Mn6+ and
      Mn4+ on the surface of Mn-SC and Mn-H-SC were the active sites for oxidation and
      adsorption of gaseous Hg0, which oxidized the elemental mercury into Hg2+ and
      captured it. Thermal treatment reduced the average oxidation degree of Mn(x+) on
      the surface of Mn-SC from 3.80 to 3.46. However, due to the formation of
      amorphous MnOx, the surface oxidation active sites for gaseous Hg0 increased,
      which gave Mn-H-SC higher mercury adsorption efficiency than that of Mn-SC at
      high temperature.

PMID- 23534205
TI  - Effects of building aspect ratio, diurnal heating scenario, and wind speed on
      reactive pollutant dispersion in urban street canyons.
AB  - A photochemistry coupled computational fluid dynamics (CFD) based numerical model
      has been developed to model the reactive pollutant dispersion within urban street
      canyons, particularly integrating the interrelationship among diurnal heating
      scenario (solar radiation affections in nighttime, daytime, and sun-rise/set),
      wind speed, building aspect ratio (building-height-to-street-width), and
      dispersion of reactive gases, specifically nitric oxide (NO), nitrogen dioxide
      (NO2) and ozone (O3) such that a higher standard of air quality in metropolitan
      cities can be achieved. Validation has been done with both experimental and
      numerical results on flow and temperature fields in a street canyon with bottom
      heating, which justifies the accuracy of the current model. The model was applied
      to idealized street canyons of different aspect ratios from 0.5 to 8 with two
      different ambient wind speeds under different diurnal heating scenarios to
      estimate the influences of different aforementioned parameters on the chemical
      evolution of NO, NO2 and O3. Detailed analyses of vertical profiles of pollutant
      concentrations showed that different diurnal heating scenarios could
      substantially affect the reactive gases exchange between the street canyon and
      air aloft, followed by respective dispersion and reaction. Higher building aspect
      ratio and stronger ambient wind speed were revealed to be, in general,
      responsible for enhanced entrainment of O3 concentrations into the street canyons
      along windward walls under all diurnal heating scenarios. Comparatively,
      particular attention can be paid on the windward wall heating and nighttime
      uniform surface heating scenarios.

PMID- 23534206
TI  - Soil warming effect on net ecosystem exchange of carbon dioxide during the
      transition from winter carbon source to spring carbon sink in a temperate urban
      lawn.
AB  - The significant warming in urban environment caused by the combined effects of
      global warming and heat island has stimulated widely development of urban
      vegetations. However, it is less known of the climate feedback of urban lawn in
      warmed environment. Soil warming effect on net ecosystem exchange (NEE) of carbon
      dioxide during the transition period from winter to spring was investigated in a
      temperate urban lawn in Beijing, China. The NEE (negative for uptake) under soil
      warming treatment (temperature was about 5 degrees C higher than the ambient
      treatment as a control) was -0.71 micromol/(m2 x sec), the ecosytem was a CO2
      sink under soil warming treatment, the lawn ecosystem under the control was a CO2
      source (0.13 micromol/(m2 x sec)), indicating that the lawn ecosystem would
      provide a negative feedback to global warming. There was no significant effect of
      soil warming on nocturnal NEE (i.e., ecosystem respiration), although the soil
      temperature sensitivity (Q10) of ecosystem respiration under soil warming
      treatment was 3.86, much lower than that in the control (7.03). The CO2 uptake
      was significantly increased by soil warming treatment that was attributed to
      about 100% increase of alpha (apparent quantum yield) and Amax (maximum rate of
      photosynthesis). Our results indicated that the response of photosynthesis in
      urban lawn is much more sensitive to global warming than respiration in the
      transition period.

PMID- 23534207
TI  - Dynamics of arsenic in salt marsh sediments from Dongtan wetland of the Yangtze
      River Estuary, China.
AB  - The mobility and transformation of arsenic (As) in salt marsh sediments were
      investigated in Dongtan wetland of the Yangtze River estuary, China. As in
      surface water, pore water and the rhizosphere sediments were quantified. The
      microcosm incubation experiments were conducted during the flooding of the
      sediments to examine As dynamics that occurred during changing redox conditions.
      The concentrations of dissolved As in pore water (0.04-0.95 micromol/L) were
      significantly greater than that in surface water (0.03-0.06 micromol/L). Under
      anoxic conditions, the reactive As could be initially mobilized by the reductive
      dissolution of Fe(III) (hydr)oxides. Subsequently, most of the dissolved As was
      likely to be associated with secondary iron (hydr)oxide phases and remained in
      solid phases. The seasonal variability of acid volatile sulfide concentrations
      suggest the anoxic conditions are enhanced during summer by Spartina alterniflora
      compared to Phragmites australis and Scirpus mariqueter, causing a notable
      increase in As mobility. Generally, there was a typical variation in redox
      conditions with season in salt marsh sediments of Dongtan wetland, in which the
      dynamics of As mobility and transformation possibly were controlled by iron, and
      all of this could be significantly influenced by the rapid spread of S.
      alterniflora.

PMID- 23534208
TI  - Photocatalytic degradation of phenanthrene on soil surfaces in the presence of
      nanometer anatase TiO2 under UV-light.
AB  - The effect of nanometer anatase TiO2 was investigated on the photocatalytic
      degradation of phenanthrene on soil surfaces under a variety of conditions. After
      being spiked with phenanthrene, soil samples loaded with different amounts of
      TiO2 (0 wt.%, 1 wt.%, 2 wt.%, 3 wt.%, and 4 wt.%) were exposed to UV-light
      irradiation for 25 hr. The results indicated that the photocatalytic degradation
      of phenanthrene followed the pseudo first-order kinetics. TiO2 significantly
      accelerated the degradation of phenanthrene with the half-life reduced from 45.90
      to 31.36 hr for TiO2 loading of 0 wt.% and 4 wt.%, respectively. In addition, the
      effects of H2O2, light intensity and humic acid on the degradation of
      phenanthrene were investigated. The degradation of phenanthrene increased with
      the concentration of H2O2, light intensity and the concentration of humic acids.
      It has been demonstrated that the photocatalytic method in the presence of
      nanometer anatase TiO2 was a very promising technology for the treatments of soil
      polluted with organic substances in the future.

PMID- 23534209
TI  - Responses of protists with different feeding habits to the changes of activated
      sludge conditions: a study based on biomass data.
AB  - Changes of protists, which were categorized into different functional groups
      primarily according to their feeding habits, in two full-scale municipal
      wastewater treatment systems experiencing sludge bulking were investigated over a
      period of 14 months. Protist biomass represented 3.7% to 5.2% of total biomass on
      average under normal sludge conditions, and the percentage increased
      significantly (p < 0.05) under sludge bulking conditions. The biomass of
      Chilodonella spp., capable of eating filamentous bacteria, tended to decrease in
      both systems when sludge bulking occurred, showing that the abnormal growth of
      filamentous bacteria did not lead to a biomass bloom of this group of protists.
      On the other hand, the bactivorous protists represented more than 96% of total
      protist biomass, and the biomass of this group, particularly the attached
      ciliates, increased significantly (p < 0.05) when sludge bulking occurred. The
      significant increase of the attached ciliates may have possibly facilitated the
      growth of filamentous bacteria through selectively preying on non-filamentous
      bacteria and further exacerbated sludge bulking. The redundancy analysis and
      correlation analysis results showed that the biomass changes of the attached
      ciliates were primarily related to the sludge volume index and to some extent
      related to five-day biochemical oxygen demand loading and hydraulic retention
      time.

PMID- 23534210
TI  - Bacterial community succession during the enrichment of chemolithoautotrophic
      arsenite oxidizing bacteria at high arsenic concentrations.
AB  - To generate cost-effective technologies for the removal of arsenic from water, we
      developed an enrichment culture of chemolithoautotrophic arsenite oxidizing
      bacteria (CAOs) that could effectively oxidize widely ranging concentrations of
      As(III) to As(V). In addition, we attempted to elucidate the enrichment process
      and characterize the microbial composition of the enrichment culture. A CAOs
      enrichment culture capable of stably oxidizing As(lII) to As(V) was successfully
      constructed through repeated batch cultivation for more than 700 days, during
      which time the initial As(III) concentrations were increased in a stepwise manner
      from 1 to 10-12 mmol/L. As(III) oxidation activity of the enrichment culture
      gradually improved, and 10-12 mmol/L As(III) was almost completely oxidized
      within four days. Terminal restriction fragment length polymorphism analysis
      showed that the dominant bacteria in the enrichment culture varied drastically
      during the enrichment process depending on the As(III) concentration. Isolation
      and characterization of bacteria in the enrichment culture revealed that the
      presence of multiple CAOs with various As(III) oxidation abilities enabled the
      culture to adapt to a wide range of As(III) concentrations. The CAOs enrichment
      culture constructed here may be useful for pretreatment of water from which
      arsenic is being removed.

PMID- 23534211
TI  - Degradation of polycyclic aromatic hydrocarbons by Pseudomonas sp. JM2 isolated
      from active sewage sludge of chemical plant.
AB  - It is important to screen strains that can decompose polycyclic aromatic
      hydrocarbons (PAHs) completely and rapidly with good adaptability for
      bioremediation in a local area. A bacterial strain JM2, which uses phenanthrene
      as its sole carbon source, was isolated from the active sewage sludge from a
      chemical plant in Jilin, China and identified as Pseudomonas based on 16S rDNA
      gene sequence analysis. Although the optimal growth conditions were determined to
      be pH 6.0 and 37 degrees C, JM2 showed a broad pH and temperature profile. At pH
      4.5 and 9.3, JM2 could degrade more than 40% of fluorene and phenanthrene (50
      mg/L each) within 4 days. In addition, when the temperature was as low as 4
      degrees C, JM2 could degrade up to 24% fluorene and 12% phenanthrene. This showed
      the potential for JM2 to be applied in bioremediation over winter or in cold
      regions. Moreover, a nutrient augmentation study showed that adding formate into
      media could promote PAH degradation, while the supplement of salicylate had an
      inhibitive effect. Furthermore, in a metabolic pathway study, salicylate,
      phthalic acid, and 9-fluorenone were detected during the degradation of fluorene
      or phenanthrene. In conclusion, Pseudomonas sp. JM2 is a high performance strain
      in the degradation of fluorene and phenanthrene under extreme pH and temperature
      conditions. It might be useful in the bioremediation of PAHs.

PMID- 23534212
TI  - Comparative proteomic study and functional analysis of translationally controlled
      tumor protein in rice roots under Hg2+ stress.
AB  - So far, very little is known about mercury stress-induced intercellular metabolic
      changes in rice roots at the proteome level. To investigate the response of rice
      roots to mercury stress, changes in protein expression in rice roots were
      analyzed using a comparative proteomics approach. Six-leaf stage rice seedlings
      were treated with 50 micromol/L HgCl2 for 3 hr; 29 protein spots showed a
      significant changes in abundance under stress when compared with the Hg2+ 
      tolerant rice mutant and wild type (Zhonghua 11). Furthermore, all these protein
      spots were identified by mass spectrometry to match 27 diverse protein species.
      The identified proteins were involved in several processes, including stress
      response, redox homeostasis, signal transduction, regulation and metabolism; some
      were found to be cellular structure proteins and a few were unknown. Among the up
      regulated proteins, OsTCTP (translationally controlled tumor protein) was chosen
      to perform hetereologous expression in yeast which was presumed to participate in
      the Hg2+ tolerance of rice, providing evidence for its role in alleviating Hg2+
      damage. Among the many tests, we found that OsTCTP-overexpressed yeast strains
      were more resistant to Hg2+ than wild-type yeast. Thus, we propose that OsTCTP
      contributes to Hg2+ resistance. Here we present, for the first time, the
      functional characterization of OsTCTP in connection with Hg2+ stress in plants.

PMID- 23534213
TI  - Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic
      induced testicular impairment.
AB  - Arsenic has a suppressive influence on spermatogenesis and induces impairment in
      male reproductive system due to oxidative stress. The present study was aimed to
      test the arsenic induced toxicity and protection by Chlorophytum borivilianum.
      The effect of sodium arsenite (4 mg/(kg body weight (bw) x day)) via double
      distilled water without or with C. borivilianum (800 mg/(kg bw x day)) was
      evaluated in Swiss albino mice for 30 days. The radical scavenging activity of
      the aqueous C. borivilianum root extract was measured using DPPH (1,1-diphenyl-2
      picryl hydrayzyl) radical. Qualitative assessment of various cell types in the
      testis, sperm count and motility, testicular activity of lipid peroxidation
      (LPO), reduced glutathione (GSH), acid and alkaline phosphatase, cholesterol and
      serum testosterone were monitored. Arsenic treatment showed a significant
      increase in LPO, acid and alkaline phosphatase, cholesterol and decrease in sperm
      count, sperm motility, GSH and serum testosterone. Combined treatment showed
      significant decrease in LPO, acid and alkaline phosphatase, cholesterol and
      elevation in sperm count, sperm motility, GSH and serum testosterone. Testicular
      histopathology showed that C. borivilianum had reduced degeneration of germ cell
      in the seminiferous tubules and loss of sperms induced by arsenic intoxication.
      The results thus led us to conclude that administration of C. borivilianum root
      extract is found to be protective against arsenic induced toxicity.

PMID- 23534214
TI  - Selective adsorption of silver ions from aqueous solution using polystyrene
      supported trimercaptotriazine resin.
AB  - Trimercaptotriazine-functionalized polystyrene chelating resin was prepared and
      employed for the adsorption of Ag(I) from aqueous solution. The adsorbent was
      characterized according to the following techniques: Fourier transform infrared
      spectroscopy, elemental analysis, scanning electron microscopy and the Brunauer
      Emmet-Teller method. The effects of initial Ag(I) concentration, contact time,
      solution pH and coexisting ions on the adsorption capacity of Ag(I) were
      systematically investigated. The maximum adsorption capacity of Ag(I) was up to
      187.1 mg/g resin at pH 0.0 and room temperature. The kinetic experiments
      indicated that the adsorption rate of Ag(I) onto the chelating resin was quite
      fast in the first 60 min and reached adsorption equilibrium after 360 min. The
      adsorption process can be well described by the pseudo second-order kinetic model
      and the equilibrium adsorption isotherm was closely fitted by the Langmuir model.
      Moreover, the chelating resin could selectively adsorb more Ag(I) ions than other
      heavy metal ions including: Cu(I), Zn(II), Ni(II), Pb(II) and Cr(III) during
      competitive adsorption in the binary metal species systems, which indicated that
      it was a highly selective adsorbent of Ag(I) from aqueous solution.

PMID- 23534215
TI  - Preparation, characterization and application of CuCrO2/ZnO photocatalysts for
      the reduction of Cr(VI).
AB  - The delafossite CuCrO2 elaborated by sol-gel from 40 nm diameter colloid is
      optically active in the visible region. It is characterized physically and
      photoelectrochemically. The microstructure is fairly homogenous with a mean
      crystallite size of ca. 2 microm. The optical gap (1.30 eV), determined from the
      diffuse reflectance, is well suited to the sunlight spectrum. The Mott Schottky
      plot is characteristic of P-type conductivity with a flat band potential of -0.26
      V(SCE). As application, the photoreduction of chromate is successfully achieved
      in air-equilibrated suspension CuCrO2/ZnO (1/1). CuCrO2 is photoactivated by
      visible light and the electrons in the conduction band (-1.34 V(SCE)) are
      injected to ZnO. In the presence of salicylic acid, a conversion of Cr(VI) to
      Cr(III) of 57% is obtained under optimal conditions (pH 3 at 25 degrees C, 5 x
      10(-4) mol/L) because of the HCrO4- dark adsorption onto ZnO (4HCrO4- + 3C7H6O3 +
      18O2 + 16H+ --> 4Cr3+ + 21CO2 + 19H2O, deltaG0 = -557 kcal/mol). Prolonged
      illumination is accompanied by a deceleration in the photoactivity owing to the
      competitive water reduction, an issue of energetic concern. The hetero-system
      exhibits self sensitization for hydrogen production with an evolution rate of 149
      micromol/(hr x g).

PMID- 23534216
TI  - Synthesis of surface sulfated BiWO with enhanced photocatalytic performance.
AB  - Sulfated BiWO (SBiWO) was synthesized by an impregnation method to enhance the
      visible-light-driven photoactivities of BiWO (BiWO). The characterization results
      verified that sulfate anion mainly anchored on the catalyst surface greatly
      extended the visible-light-responsive range without destroying the crystal
      lattice. Moreover, the SBiWO-based photoactivities were evaluated with the
      removal of Malachite Green (MG) under UV-Vis irradiation emitted from two
      microwave-powered electrodeless discharge lamps (MPEDL2) and under visible light
      (lamda > 420 nm). The results demonstrated that the kinetic constant was
      increased 2.25 times, varying from 0.1478 (BiWO) to 0.3328 min(-1) (SBiWO-1).
      Similar results were also obtained for the visible light-driven reaction.
      Furthermore, radical scavengers such as t-butanol restricted the visible-light
      induced degradation of MG over BiWO and SBiWO-1. This indicated that the
      sulfating process increased the generation of reactive oxygen species, which was
      further verified by molecular probe with salicylic acid. Thus, more blue-shifting
      at lam = 618 nm was observed over SBiWO. On the basis of the above results, the
      photocatalytic mechanism over the sulfated catalyst was also discussed.

PMID- 23534217
TI  - Determination of 3,4-dichlorinated biphenyl in soil samples by real-time immuno
      PCR assay.
AB  - A real-time fluorescent quantitative immuno-polymerase chain reaction (RT-IPCR)
      assay was developed for the detection of non-dioxin-like polychlorinated biphenyl
      (PCB) congener in soil samples. Based on the construction of 3,4-dichlorinated
      biphenyl (IUPAC PCB12) hapten and its immunogen, the specific polyclonal
      antibodies (pAbs) to PCB12 was obtained and used to develop a direct competitive
      RT-IPCR assay. Using the optimized assay, a standard curve for PCB12 was
      prepared. The linear range for the determination of PCB12 was from 10.0 to 1.0 x
      106 fg/mL with a correlation coefficient of 0.98 and a detection limit of 1.53
      fg/mL. The RT-IPCR assays were tested for their cross-reactivity profiles using
      four selected congeners and four Aroclor products. The results for the soil
      samples correlated with the concentrations of PCBs obtained by gas
      chromatography/mass spectrometry. This highly specific, sensitive, and robust
      assay can be applied to on-site tests of PCBs and serve as a model for other
      pollutant immunoassays.

PMID- 23534218
TI  - Enantioseletive bioaccumulation of tebuconazole in earthworm Eisenia fetida.
AB  - Methods of extraction and determination of tebuconazole enantiomers in earthworm
      (Eisenia fetida) were developed by capillary electrophoresis (CE) and high
      performance liquid chromatography (HPLC). Both CE and HPLC have excellent
      resolution and recovery. The linearity ranges were 2.9-102.4 mg/kg and 3.0-99.6
      mg/kg for (+)-R-tebuconazole and (-)-S-tebuconazole respectively in CE, and from
      0.56 to 1000 mg/kg for both enantiomers in HPLC. Enantioselective bioaccumulation
      in earthworms from soil was investigated under laboratory condition at
      concentrations of 10 and 50 mg/kg dw in soil. The uptake kinetics of (+)-R
      tebuconazole fitted the first-order kinetics well with r2 0.97 and 0.94 under 10
      and 50 mg/kg dw exposure condition, respectively, while (-)-S-tebuconazole with
      r2 0.75 and 0.22 did not show the same. Bioaccumulation of tebuconazole in
      earthworm tissues was enantioselective with a preferential accumulation of (+)-R
      tebuconazole. The (+)-R-tebuconazole might also have biomagnifying effect
      potential in earthworm food chain with biota-sediment accumulation factor (BSAF)
      of 1.64 kg OC/kg lip in 10 mg/kg dw exposure group and 2.61 kg OC/kg lip in 50
      mg/kg dw exposure group from soil to earthworm after 36 days. Although (-)-S
      tebuconazole shares the same physicochemical properties with (+)-R-tebuconazole,
      it did not biomagnify. BSAFs of (-)-S-tebuconazole were 0.50 kg OC/kg lip (10
      mg/kg dw tebuconazole exposure) and 0.28 kg OC/kg lip (50 mg/kg dw tebuconazole
      exposure) after 36 days, which was possibly owing to biotransformation or
      metabolism in earthworm tissues.

PMID- 23534219
TI  - Occurrence of selected aliphatic amines in source water of major cities in China.
AB  - The formation of toxic nitrogenous disinfection byproducts (N-DBPs), such as
      nitrosamines, halonitromethanes and haloacetonitriles, from reactions between
      chlorine/chloramine and dissolved organic nitrogen in drinking water has caused
      great concern with regarding public health. This study revealed the occurrence of
      17 aliphatic amines, some of which have been confirmed to be the precursors of N
      DBPs, in source water across China. A sensitive method based on benzenesulfonyl
      chloride derivatization and liquid-liquid extraction followed by GC-MS analysis
      was established for the simultaneous analysis of the selected amines in aqueous
      samples. In total, 37 source water samples from the capital cities of 20
      provinces were collected for the survey. Among the 17 amines, 14 were detected
      with an average frequency of detection of 36%. The most relevant amines in terms
      of frequency and maximum concentrations detected were dimethylamine (100%, 24.82
      microg/L), methylamine (78%, 0.92 microg/L), N-methylethylamine (70%, 8.84
      microg/L), propylamine (59%, 10.69 microg/L), diethylamine (54%, 3.76 microg/L),
      N-methylbutylamine (35%, 3.07 microg/L), N-ethylpropylamine (35%, 0.52 microg/L),
      and piperidine (32%, 2.35 microg/L). This is the first large scale survey of the
      aliphatic amines occurrence in source water in the world. The wide presence of
      nitrosamine precursors like dimethylamine, N-methylethylamine and diethylamine,
      and the precursors of haloacetonitriles and halonitromethanes like methylamine
      and propylamine suggests that better source water management is required to
      ensure the safety of drinking water.

PMID- 23534220
TI  - Selection of magnetic anion exchange resins for the removal of dissolved organic
      and inorganic matters.
AB  - Four magnetic anion exchange resins (MAERs) were used as adsorbents to purify
      drinking water. The effect of water quality (pH, temperature, ionic strength,
      etc.) on the performance of MAER for the removal of dissolved organic matter
      (DOM) was also investigated. Among the four studied MAERs, the strong base resin
      named NDMP-1 with high water content and enhanced exchange capacity exhibited the
      highest removal rate of dissolved organic carbon (DOC) (48.9% removal rate) and
      UV-absorbing substances (82.4% removal rate) with a resin dose of 10 mL/L after
      30 min of contact time. The MAERs could also effectively remove inorganic matter
      such as sulfate, nitrate and fluoride. Because of the higher specific UV
      absorbance (SUVA) value, the DOM in the raw water was found to be removed more
      effectively than that in the clarified water by NDMP resin. The temperature
      showed a weak influence on the removal of DOC from 6 to 26 degrees C, while a
      relatively strong one at 36 degrees C. The removal of DOM by NDMP was also
      affected to some extent by the pH value. Moreover, increasing the sulfate
      concentration in the raw water could decrease the removal rates of DOC and UV
      absorbing substances.

PMID- 23534221
TI  - Reductive transformation and detoxification mechanism of 2,4-dinitrochlorobenzene
      in combined zero valent iron and anaerobic-aerobic process.
AB  - A combined zero valent iron (ZVI) and anaerobic-aerobic process was adopted for
      the treatment of 2,4-dinitrochlorobenzene (DNCB)-containing wastewater. The
      transformation pathway, reduction of acute toxicity and enhancement of
      biodegradability were investigated. After pretreatment by ZVI, DNCB in wastewater
      could be completely converted into 2,4-diaminochlorobenzene (DACB). The ratio of
      BOD5/COD increased from 0.005 +/- 0.001 to 0.168 +/- 0.007, while EC(50, 48 hr)
      (V/V) increased from 0.65% to 5.20%, indicating the enhancement of
      biodegradability and reduction of acute toxicity with the pretreatment by ZVI.
      DACB was further dechlorinated to m-phenylenediamine during the anaerobic process
      using methanol as electron donor, with EC(50, 48 hr) increasing from 5.20% to
      48.2%. After the subsequent anaerobic-aerobic process, m-phenylenediamine was
      degraded completely, with effluent COD of 67.5 +/- 10.8 mg/L. This effluent of
      the subsequent anaerobic-aerobic process was not toxic to zebrafish. The combined
      ZVI and anaerobic-aerobic process offers bright prospects for the treatment of
      chlorinated nitroaromatic compound-containing wastewater.

PMID- 23534222
TI  - Fractionation of residual Al in natural water treatment from reservoir with poly
      aluminum-silicate-chloride (PASiC): effect of OH/Al, Si/Al molar ratios and
      initial pH.
AB  - An aluminum fractionation study was conducted for a surface reservoir water
      treatment to understand the performance of poly-aluminum-silicate-chloride
      (PASiC) in terms of the residual Al fractions as a function of initial pH. The
      coagulation performance expressed as turbidity and organic matter removal was
      established as supporting data. Some extra data were evaluated in terms of the
      residual Al ratio of the composite PASiC coagulant. The main residual Al sources
      were the Al fractions derived from the use of PASiC. The turbidity and organic
      matter removal ability was optimal at initial pH 6.00-7.00, while the
      concentrations of various residual Al species and the residual Al ratio of PASiC
      were minimal at an initial pH range of 7.00-8.00. Under the conditions of OH/Al
      molar ratio = 2.00 and Si/Al molar ratio = 0.05, PASiC had superior coagulation
      performance and comparatively low residual Al concentrations. The Al fraction in
      the composite PASiC coagulant seldom remained under such conditions. Experimental
      data also indicated that the suspended (filterable) Al fraction was the dominant
      species, and organic-bound or organo-Al complex Al was considered to be the major
      species of dissolved Al in water treated by PASiC coagulation. Additionally, the
      dissolved inorganic monomeric Al species dominated the dissolved monomeric Al
      fraction.

PMID- 23534223
TI  - Effect of solid contents on the controlled shear stress rheological properties of
      different types of sludge.
AB  - Controlled shear stress (CSS) test was used to study the effect of solid contents
      on the corresponding rheological parameters for sludge. Three types of sludge
      with or without conditioning, including activated sludge (AS), anaerobic digested
      sludge (ADS), and water treatment residuals (WTRs), were collected for the CSS
      test. Results showed that the yield stress and the cohesion energy of the sludge
      networks were improved with increased total suspending solid (TSS) contents in
      most cases. For the conditioned AS/ADS and the raw WTRs, exponential law was
      observed in the relationships between cohesion energy of material networks or
      yield stress and the TSS contents, whereas for the conditioned WTRs, only
      exponential law dependence was found between the parameters of shear modulus or
      critical strain and the TSS contents.

PMID- 23534224
TI  - Optimizing the operation of the Qingshitan Reservoir in the Lijiang River for
      multiple human interests and quasi-natural flow maintenance.
AB  - For reservoir operation, maintaining a quasi-natural flow regime can benefit
      river ecosystems, but may sacrifice human interests. This study took the
      Qingshitan Reservoir in the Lijiang River as a case, and developed an
      optimization model to explore a trade-off solution between social-economic
      interests and nature flow maintenance on a monthly base. The objective function
      considered irrigation, cruise navigation and water supply aspects. An index of
      flow alteration degree was proposed to measure the difference between the
      regulated discharge and the natural flow. The index was then used as an
      additional constraint in the model besides the conventional constraints on
      reservoir safety. During model solving, different criteria were applied to the
      index, representing various degrees of alteration of the natural flow regime in
      the river. Through the model, a relationship between social-economic interests
      and flow alteration degree was established. Finally, a trade-off solution of the
      reservoir operation was defined that led to a favorable social-economic benefit
      at an acceptable alteration of the natural flow.

PMID- 23534225
TI  - Zeolite (Na) modified by nano-Fe particles adsorbing phosphate in rainwater
      runoff.
AB  - Zeolite (Na) modified by self-synthesized nano-Fe particles was used as
      infiltration media to adsorb phosphate in rainwater runoff. The adsorption
      capacities increased up to 75 times that of natural zeolite at a saturated
      equilibrium phosphate concentration of 0.42 mg/L. The correlation of capacity and
      material-specific surface area indicated that specific surface area was not the
      key factor contributing to the capacity improvement. SEM and XRD analysis showed
      that chemical reaction between Fe and P to form new products like cacoxenite is
      the main reason for the increased capacity, and that the method of adding metal
      ions or particles to improve the adsorption capacity for phosphate is feasible.

PMID- 23534226
TI  - Contamination by persistent toxic substances in surface sediment of urban rivers
      in Chaohu City, China.
AB  - The concentration and spatial distribution of persistent toxic substances (PTS)
      in the river sediment in Chaohu City, China were investigated. A total of nine
      surface sediments were collected and the selected PTS pollutants including six
      heavy metals and nineteen polybrominated diphenyl ethers (PBDEs) were analyzed.
      The mean heavy metal concentrations (in mg/kg, dry weight) ranged within 0.18
      1.53 (Hg), 50.08-200.18 (Cu), 118.70-313.65 (Zn), 50.77-310.85 (Cr), 37.12-92.72
      (Pb) and 13.29-197.24 (As), and Cu, Zn and As have been regarded as the main
      metal pollutants. The levels of PBDEs (1.2-12.1 ng/g) and BDE-209 (2.4-30.5 ng/g)
      were at the middle level of the global range. BDE-209 was the predominant
      congener (67.0%-85.7%), which agrees with the fact that technical deca-BDE
      mixtures are the dominant PBDE formulation in China. The relative high level of
      PTS pollutants in the western part of the city is probably owing to the intensive
      agricultural activities and lack of sewerage system there. The ecological risk
      assessment with the sediment quality guidelines (SOGs) indicates that the urban
      river sediments in the city have been heavily contaminated by heavy metals with
      probable ecotoxicological impacts on freshwater organisms and the main toxic
      pollutants are Hg and As. The results of current study imply that the city, and
      perhaps many other small cities in China as well, requires immediate pollution
      control measures with emphasis on not only conventional organic pollutants but
      also on PTS such as heavy metals and PBDEs.

PMID- 23534227
TI  - Fatty acids and algal lipids as precursors of chlorination by-products.
AB  - Six common algal fatty acids (FAs) with different numbers of double bonds,
      lipophilic fractions and proteins extracted from the diatom Navicula pelliculosa
      and algal cells were chlorinated to evaluate their potential in generating
      disinfection by-products (DBPs). The result showed that the more double bonds in
      the FAs, the higher the amounts of chloroform and dichloroacetic acid (DCAA)
      produced, but such a pattern was not observed for trichloroacetic acid (TCAA).
      Based on the previously reported composition of fatty acids in algal lipids, the
      DBP generation potentials of algal lipids were calculated. These predicted values
      were much lower than those measured in the chlorinated algal lipophilic fraction,
      suggesting unknown lipophilic fraction(s) served as potent DBPs precursors.
      Another calculation attempted to predict DBP production in algal cells based on
      algal lipid and protein composition, given quantified measured DBP production per
      unit algal lipid and proteins. The analysis showed that the observed DBP
      production was similar to that predicted (< 35% difference), suggesting that
      algal biochemical compositions may serve as a bioindicator for preliminary
      estimation of chloroform, DCAA and TCAA formation upon chlorinating algae.

PMID- 23534228
TI  - Uptake of isoprene, methacrylic acid and methyl methacrylate into aqueous
      solutions of sulfuric acid and hydrogen peroxide.
AB  - Multiphase acid-catalyzed oxidation by hydrogen peroxide has been suggested to be
      a potential route to secondary organic aerosol formation from isoprene and its
      gas-phase oxidation products, but the lack of kinetics data significantly limited
      the evaluation of this process in the atmosphere. Here we report the first
      measurement of the uptake of isoprene, methacrylic acid and methyl methacrylate
      into aqueous solutions of sulfuric acid and hydrogen peroxide. Isoprene cannot
      readily partition into the solution because of its high volatility and low
      solubility, which hinders its further liquid-phase oxidation. Both methacrylic
      acid and methyl methacrylate can enter the solutions and be oxidized by hydrogen
      peroxide, and steady-state uptake was observed with the acidity of solution above
      30 wt.% and 70 wt.%, respectively. The steady-state uptake coefficient of
      methacrylic acid is much larger than that of methyl methacrylate for a solution
      with same acidity. These observations can be explained by the different
      reactivity of these two compounds caused by the different electron-withdrawing
      conjugation between carboxyl and ester groups. The atmospheric lifetimes were
      estimated based on the calculated steady-state uptake coefficients. These results
      demonstrate that the multiphase acid-catalyzed oxidation of methacrylic acid
      plays a role in secondary organic aerosol formation, but for isoprene and methyl
      methacrylate, this process is not important in the troposphere.

PMID- 23534229
TI  - Comparison of PM10 concentrations and metal content in three different sites of
      the Venice Lagoon: an analysis of possible aerosol sources.
AB  - The Venice Lagoon is exposed to atmospheric pollutants from industrial
      activities, thermoelectric power plants, petrochemical plants, incinerator,
      domestic heating, ship traffic, glass factories and vehicular emissions on the
      mainland. In 2005, construction began on the mobile dams (MOSE), one dam for each
      channel connecting the lagoon to the Adriatic Sea as a barrier against high tide.
      These construction works could represent an additional source of pollutants. PM10
      samples were taken on random days between 2007 and 2010 at three different sites:
      Punta Sabbioni, Chioggia and Malamocco, located near the respective dam
      construction worksites. Chemical analyses of V, Cr, Fe, Co, Ni, Cu, Zn, As, Mo,
      Cd, Sb, Tl and Pb in PM10 samples were performed by Inductively coupled plasma
      quadrupole mass spectrometry (ICP-QMS) and results were used to identify the main
      aerosol sources. The correlation of measured data with meteorology, and source
      apportionment, failed to highlight a contribution specifically associated to the
      emissions of the MOSE construction works. The comparison of the measurements at
      the three sites showed a substantial homogeneity of metal concentrations in the
      area. Source apportionment with principal component analysis (PCA) and positive
      matrix factorization (PMF) showed that a four principal factors model could
      describe the sources of metals in PM10. Three of them were assigned to specific
      sources in the area and one was characterised as a source of mixed origin
      (anthropogenic and crustal). A specific anthropogenic source of PM10 rich in Ni
      and Cr, active at the Chioggia site, was also identified.

PMID- 23534230
TI  - Seasonal trend of ambient PCDD/Fs in Tianjin City, northern China using active
      sampling strategy.
AB  - The spatial concentrations, seasonal trends, profiles and congener pairs of
      ambient polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated
      dibenzofurans (PCDFs) were investigated within a seasonally active sampling
      scheme during Jun 2008 and Jan 2009 in Tianjin City, northern China. The PCDD/F
      concentrations ranged 14.2-172 fg I-TEQ/m3 (average 69.3 fg I-TEQ/m3) in summer
      and (89.8-1.01) x 10(3) fg I-TEQ/m3 (average 509 fg I-TEQ/m3) in winter,
      respectively, except for the E-waste dismantling site where much higher values
      were observed (1.04 x 10(3) fg I-TEQ/m3 in summer and 7.123 x 10(3) fg I-TEQ/m3
      in winter). The results indicated a significantly seasonal trend with higher TEQ
      values in winter as compared with summer, which could be related to increased
      emission sources and seasonal variations of the atmospheric boundary layer
      height. 2,3,4,7,8-PeCDF was the dominant contributor to the total PCDD/F toxic
      equivalents, and 2,3,7,8-TCDD was detected at almost all the sampling sites in
      winter. Most of the similarly substituted PCDD/F congener pairs exhibited high
      correlations, suggesting that they might have similar environmental fate or
      sources. But different seasonal and spatial distributions of PCDD/F
      concentrations indicated that the emission sources might be intermittent.

PMID- 23534231
TI  - Ultrafine particle emission characteristics of diesel engine by on-board and test
      bench measurement.
AB  - This study investigated the emission characteristics of ultrafine particles based
      on test bench and on-board measurements. The bench test results showed the
      ultrafine particle number concentration of the diesel engine to be in the range
      of (0.56-8.35) x 10(8) cm(-3). The on-board measurement results illustrated that
      the ultrafine particles were strongly correlated with changes in real-world
      driving cycles. The particle number concentration was down to 2.0 x 10(6) cm(-3)
      and 2.7 x 10(7) cm(-3) under decelerating and idling operations and as high as
      5.0 x 10(8) cm(-3) under accelerating operation. It was also indicated that the
      particle number measured by the two methods increased with the growth of engine
      load at each engine speed in both cases. The particle number presented a "U"
      shaped distribution with changing speed at high engine load conditions, which
      implies that the particle number will reach its lowest level at medium engine
      speeds. The particle sizes of both measurements showed single mode distributions.
      The peak of particle size was located at about 50-80 nm in the accumulation mode
      particle range. Nucleation mode particles will significantly increase at low
      engine load operations like idling and decelerating caused by the high
      concentration of unburned organic compounds.

PMID- 23534232
TI  - N-doped mesoporous alumina for adsorption of carbon dioxide.
AB  - N-doped mesoporous alumina has been synthesized using chitosan as the biopolymer
      template. The adsorbent has been thoroughly investigated for the adsorption of
      CO2 from a simulated flue gas stream (15% CO2 balanced with N2) and compared with
      commercially available mesoporous alumina procured from SASOL, Germany. CO2
      adsorption was studied under different conditions of pretreatment and adsorption
      temperature, inlet CO2 concentration and in the presence of oxygen and moisture.
      The adsorption capacity was determined to be 29.4 mg CO2/g of adsorbent at 55
      degrees C. This value was observed to be 4 times higher in comparison to that of
      commercial mesoporous alumina at a temperature of 55 degrees C. Basicity of
      alumina surface coupled with the presence of nitrogen in template in synthesized
      sample is responsible for this enhanced CO2 adsorption. Adsorption capacity for
      CO2 was retained in the presence of oxygen; however moisture had a deteriorating
      effect on the adsorption capacity reducing it to nearly half the value.

PMID- 23534233
TI  - Extraction of heavy metals from e-waste contaminated soils using EDDS.
AB  - Environmental contamination due to uncontrolled e-waste recycling activities is
      drawing increasing attention in the world. Extraction of these metals with
      biodegradable chelant [S,S]-ethylenediaminedisuccinic acid (EDDS) and the factors
      influencing extraction efficacy were investigated in the present study. Results
      showed that the addition of EDDS at low pH (5.5) produced higher metal extraction
      than that at high pH (8.0) solution. Metal speciation analysis indicated that Cu
      was completely complexed with EDDS at different pH conditions with various
      amounts of EDDS applied. For Pb and Zn, at low EDDS dose of 0.304 mol/kg soil,
      they were present as Pb- and Zn-EDDS. However, at high EDDS dose of 1.26 mol/kg
      soil, most of Pb was bound with dissolved organic matter. Ca and Al were found to
      be strong competitors for trace metals to EDDS at low application dose and low pH
      condition.

PMID- 23534234
TI  - Characterization of contamination, source and degradation of petroleum between
      upland and paddy fields based on geochemical characteristics and phospholipid
      fatty acids.
AB  - To evaluate contamination caused by petroleum, surface soil samples were
      collected from both upland and paddy fields along the irrigation canals in the
      Hunpu wastewater irrigation region in northeast China. N-alkanes, terpanes,
      steranes, and phospholipid fatty acids (PLFA) in the surface soil samples were
      analyzed. The aliphatic hydrocarbon concentration was highest in the samples
      obtained from the upland field near an operational oil well; it was lowest at I
      3P where wastewater irrigation promoted the downward movement of hydrocarbons.
      The Hunpu region was found contaminated by heavy petroleum from oxic lacustrine
      fresh water or marine deltaic source rocks. Geochemical parameters also indicated
      significantly heavier contamination and degradation in the upland fields compared
      with the paddy fields. Principal component analysis based on PLFA showed various
      microbial communities between petroleum contaminated upland and paddy fields.
      Gram-negative bacteria indicated by 15:0, 3OH 12:0, and 16:1(9) were
      significantly higher in the paddy fields, whereas Gram-positive bacteria
      indicated by i16:0 and 18:1(9)c were significantly higher in the upland fields (p
      < 0.05). These PLFAs were related to petroleum contamination. Poly-unsaturated
      PLFA (18:2omega6, 9; indicative of hydrocarbon-degrading bacteria and fungi) was
      also significantly elevated in the upland fields. This paper recommends more
      sensitive indicators of contamination and degradation of petroleum in soil. The
      results also provide guidelines on soil pollution control and remediation in the
      Hunpu region and other similar regions.

PMID- 23534235
TI  - Bacterial diversity and distribution in the southeast edge of the Tengger Desert
      and their correlation with soil enzyme activities.
AB  - The nature of microbial communities and their relation to enzyme activities in
      desert soils is a neglected area of investigation. To address this, the bacterial
      diversity and distribution and soil physico-chemical factors were investigated in
      the soil crust, the soil beneath the crust and rhizosphere soil at the southeast
      edge of the Tengger Desert, using the denaturing gradient gel electrophoresis of
      16S rRNA genes amplified by the polymerase chain reaction. Phylogenetic analysis
      of the sequenced DGGE bands revealed a great diversity of bacteria. The
      Proteobacteria, consisting of the alpha, beta, and gamma subdivisions, were
      clearly the dominant group at all depths and in rhizosphere soil. Analysis of the
      enzyme activities indicated that the rhizosphere soil of Caragana korshinskii
      exhibited the highest protease and polyphenol oxidase activities, and in the soil
      crust there were increased activities of catalase, urease, dehydrogenase and
      sucrase. The bacterial community abundance closely correlated with soil enzyme
      activities in different soils. The presence of Cyanobacteria correlated with
      significant increases in protease, catalase and sucrase in the soil crust, and
      increased urease in the rhizosphere soil of Artemisia ordosica. The occurrence of
      Acidobacteria was associated with significant increases in urease, dehydrogenase,
      and sucrase in the rhizosphere soil of C. korshinski. The presence of gamma
      Proteobacteria correlated with a significant increase in polyphenol oxidase in
      the rhizosphere soil of A. ordosica. The study indicated a close relationship
      between the soil bacterial community and soil enzymes, suggesting the necessity
      of further investigations into bacterial function in this desert ecosystem.

PMID- 23534236
TI  - Biodegradation of p-cresol by aerobic granules in sequencing batch reactor.
AB  - The cultivation of aerobic granules in sequencing batch reactor for the
      biodegradation of p-cresol was studied. The reactor was started with 100 mg/L of
      p-cresol. Aerobic granules first appeared within one month of start up. The
      granules were large and strong and had a compact structure. The diameter of
      stable granules was in the range of 1-5 mm. The integrity coefficient and
      granules density was found to be 96% and 1046 kg/m3, respectively. The settling
      velocity of granules was found to be in the range of 2x10(-2)-6x10(-2) m/sec. The
      aerobic granules were able to degrade p-cresol upto 800 mg/L at a removal
      efficiency of 88%. Specific p-cresol degradation rate in aerobic granules
      followed Haldane model for substrate inhibition. High specific p-cresol
      degradation rate up to 0.96 g p-cresol/(g VSS x day) were sustained upto p-cresol
      concentration of 400 mg/L. Higher removal efficiency, good settling
      characteristics of aerobic granules, makes sequencing batch reactor suitable for
      enhancing the microorganism potential for biodegradation of inhibitory compounds.

PMID- 23534237
TI  - Characterisation of acute toxicity, genotoxicity and oxidative stress posed by
      textile effluent on zebrafish.
AB  - Textile industries are important sources of toxic discharges and contribute
      enormously to water deterioration, while little attention has been paid to the
      toxicity of textile effluents in discharge regulation. Bioassays with zebrafish
      were employed to evaluate the toxicity of wastewater samples collected from
      different stages at a textile factory and sewage treatment plants (STPs). Physico
      chemical parameters, acute toxicity, genotoxicity and oxidative stress biomarkers
      were analyzed. The wastewater samples from bleaching, rinsing and soaping of the
      textile factory exhibited high acute toxicity and genotoxicity. The coexisting
      components of dye compounds, as assistants and oxidants, seemed to cause some
      effect on the toxic response. After treatment employing the anoxic-oxic (A/O)
      process in STPs, the color and the chemical oxygen demand (COD) were reduced by
      40% and 84%, respectively, falling within the criteria of the Chinese Sewage
      Discharge Standard. In contrast, increases in acute toxicity and genotoxicity
      were observed in the anaerobic tank, indicating the formation of toxic
      intermediates. The genotoxicity of the effluent of the STP was not significantly
      different from that of the influent, suggesting the wastewater treatment
      processes were not effective in removing the genotoxicity of the dye wastewater.
      Results indicated that the effluent contains pro-oxidants since the activities of
      glutathione (GSH), malondialdehyde (MDA), and total anti-oxidation capacity (T
      AOC) were all elevated. In addition, decreases in superoxide dismutase (SOD) and
      glutathione-S transferase (GST) activities observed can be interpreted as a
      cytotoxicity sign due to an over-production of reactive oxygen species (ROS). The
      results of the present study suggest that the STPs were not capable of reducing
      the toxicity of wastewater sufficiently. Further treatment is needed to remove
      the potential risks posed by textile effluent to ecosystems and human health, and
      employing a toxicity index is necessary for discharge regulation.

PMID- 23534238
TI  - Characterization of cytotoxicity of airborne particulates from urban areas of
      Lahore.
AB  - A number of species (organic and inorganic) in airborne particulates cause the
      toxicity to living being. The potential of in vitro test methods were explored
      for toxicity assessment of trace toxic elements (inorganic species) present in
      ambient air on human being (lungs). A year long sampling of airborne particles
      (PM2.5) was carried (April 2008 to March 2009) in Lahore, Pakistan. A total of
      thirty nine samples were collected on 47 mm Zefluor Teflon filter membranes and
      each was analysed to characterize for the elements: Sb, As, Be, Cd, Cr, Co, Pb,
      Mn, Hg using ICP-MS in water extract and total acid digestate. The samples
      cytotoxicity was also established using lung derived cells and MTS colorimetric
      assays. This generated dose response curves and IC50 values for the elemental
      mixtures identified on the Teflon filter membrane. The results indicated that
      even at low concentrations airborne elemental mixtures displayed an additive
      toxic effect.

PMID- 23534239
TI  - [Connective tissue diseases, a matter for specialists?].

PMID- 23534240
TI  - [Joint manifestations in connective tissue diseases].
AB  - Joint manifestations are common and often constitute the first symptoms or signs
      of a connective tissue disease, which should be carefully looked for, according
      to the clinic, in particular with ultrasound and the research of autoantibodies.
      Articular manifestations are often severe and must be treated accordingly. In
      lupus, one can distinguish non-deforming non-erosive arthropathy, Jaccoud's
      arthropathy (deforming non-erosive) and erosive arthropathy (rhupus). Ultrasound
      has recently shown that destructive forms are in fact more frequent than
      initially considered. In addition, lupus can be complicated by necrosis or
      fractures, which are characterized by mechanical pain. In other connective tissue
      diseases, similar forms of arthropathies and complications are found, with some
      distinctions.

PMID- 23534241
TI  - [Cardiovascular complications in immune mediated diseases].
AB  - Immune mediated diseases carry an increased risk of major cardiovascular events
      (CV) and an increased risk of CV mortality. The increased CV risk appears to be
      linked directly to chronic inflammation. Various studies have demonstrated that
      reducing inflammation reduces the incidence of CV complications. We review the
      epidemiological evidence linking immune mediated diseases and increased CV risk,
      discuss the causal role of inflammation in the etiopathogenesis and appraise some
      potential benefits of specific anti-inflammatory therapies.

PMID- 23534242
TI  - [Connective tissue diseases: news in therapy, role of biologics agents].
AB  - Systemic lupus erythematosus and primary Sjogren's syndrom are the two major
      connective tissue diseases. A better knowledge of their physiopathology allows us
      today to propose an adapted therapy. Moreover progress concerns the oldest
      treatment, hydroxychloroquine, and biotherapy. Hydroxychloroquine is still an
      actual treatment for lupus, its positive effects are better understood today.
      Nevertheless it does not seem to be efficient to treat primitive Sjogren.
      Biotherapy targeting B lymphocytes seems efficient in these two connective tissue
      diseases. Anti TNF therapy is not recommended and seems to induce connective
      tissue diseases. The real news is the recent approval and reimbursement in
      Switzerland of the new drug belimumab (Benlysta) in case of moderate lupus.

PMID- 23534243
TI  - [Family physician and connective tissue disorders].
AB  - The exact place of the family physician in the diagnosis and management of
      connective tissue disease is poorly studied moreover will essentially depend on
      the health system and the organization of medical network of each country.
      Connective tissue diseases are rare and complex diseases that require in all
      cases referral to specialists for their diagnosis as well as monitoring. All
      patients must still keep a family doctor whose importance increases more and more
      as our specialized treatments prolong survival of patients who become chronically
      ill with multi-organic sequelae. A closely interaction between the various
      specialists and family physicians is necessary to ensure a good long-term follow
      up.

PMID- 23534244
TI  - [Erosive hand osteoarthritis].
AB  - Erosive hand osteoarthritis is common and debilitating. Diagnosis is based on the
      presence of bone erosions which can appear late. Ultrasonography allows earlier
      diagnosis. The presence of apatite deposits could be of poor prognosis. Non
      pharmacological treatment includes the explanation of the inflammatory phenomena
      involved and the use of splints and physical therapy. Drug therapy includes
      analgesics, NSAIDs and infiltration of a steroid. Chondroitin sulfates have an
      analgesic and functional effect proven. DMARDs such as hydroxychloroquine and
      methotrexate have been used successfully. Some patients also benefited from
      isotope synoviortheses. New therapeutic ways, based on the pathophysiology of the
      disease, are new under evaluation.

PMID- 23534245
TI  - [Recommendations for therapeutic monitoring of antidepressants].
AB  - Therapeutic drug monitoring (TDM), combined in certain situations with
      pharmacogenetic tests of metabolism, has proven a valuable tool for
      psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability,
      nonresponse at therapeutic doses, or pharmacokinetic drug-drug interactions are
      typical situations when measurement of medication concentrations is helpful. This
      article is an adaptation of guidelines recently issued by the AGNP-TDM group
      (Hiemke et al., www. agnp.de), but its content focuses mainly on the TDM of
      antidepressants. Finally, the potential benefits of TDM for optimization of
      pharmacotherapy can only be obtained if the method is adequately integrated into
      the clinical treatment process.

PMID- 23534246
TI  - [Stigma of "madness" from fate to recovery].
AB  - Stigma is a "natural" social reaction, partly unconscious and automatic towards
      "different" and "vulnerable" populations. Suspicion of danger, unemployment,
      excluded from society, locked in hospital, assaulted or killed are the possible
      consequences of mental disorders' stigma. Despite advances in psychiatric
      treatments, the stigma of the "madness" remains a barrier to access to recovery.
      The stigmatization process is more complex than simple labeling, and leads to
      discrimination and loss of social power. Understanding the mechanisms of
      stigmatization can determine targets for effective interventions to fight stigma
      at the individual, institutional and political levels. The roles of patient and
      family associations, as well as the recovery model for the professionals, are
      essential. The aim of this article is to review the various aspects of mental
      disorders' stigma and to examine ways to cope with them.

PMID- 23534247
TI  - [Better understanding of the patient's autonomy].

PMID- 23534248
TI  - [Blood pressure: identifying the best real numbers ].

PMID- 23534249
TI  - [No, the teeth of seniors are not all gold].

PMID- 23534250
TI  - [The latest diagnostics of Dr. House].

PMID- 23534251
TI  - [The strategy of chaos].

PMID- 23534252
TI  - [Molecular approaches to infectious keratitis].

PMID- 23534253
TI  - [Influence of postoperative lens status on intraocular pressure and corneal
      endothelium following vitrectomy with silicone oil tamponade].
AB  - PURPOSE: To evaluate the influence of postoperative lens status on intraocular
      pressure elevation and corneal endothelial cell loss in patients who underwent
      pars plana vitrectomy with silicone oil injection for the management of complex
      retinal detachment. PATIENTS AND METHODS: The medical records of 80 eyes of 79
      patients who underwent silicone oil removal were reviewed retrospectively. For
      analysis, eyes were divided by postoperative lens status into 2 groups:
      pseudophakic eyes (IOL group) and aphakic eyes(aphakic group). RESULTS: There was
      a significantly greater decrease in intraocular pressure after silicone oil
      removal in the aphakic group but not in the IOL group. As compared with the IOL
      group, the aphakic group showed a significant reduction in endothelial cell
      density at the time of silicone oil removal. CONCLUSION: Patients who underwent
      silicone oil injection with pseudophakic eyes may have a lower risk of
      intraocular pressure elevation and corneal endothelial cell loss than those with
      aphakic eyes.

PMID- 23534254
TI  - [Relationship between birth month and corneal radius or axial length].
AB  - PURPOSE: Hyperopia prevalence is higher in children born in the autumn. This
      study attempted to detect whether corneal curvature or axial length are related
      to this phenomenon. METHODS: Using data from a total of 4056 cataract patients
      aged 40 and over from three medical facilities, corneal radius and axial length,
      measured to determine the intraocular lens power needed for cataract surgery,
      were reviewed. Mean corneal radius and mean axial length were calculated for each
      birth month. The means were then graphically analyzed to determine the
      relationship of corneal radius or axial length with birth month. RESULTS: No
      correlation was noted between axial length and birth month. However, a
      correlation between corneal radius and birth month was observed in each of the
      three facilities. Specifically, subjects born from October through December
      tended to have larger corneal radii. Numerically, the corneal radius showed a
      statistical relationship in terms of birth month (p < 0.001, ANOVA), while the
      axial length showed no relationship (p = 0.907, ANOVA). CONCLUSION: A
      statistically meaningful relationship between corneal curvature and birth month
      was detected. Corneal development might be affected by seasonal daylight
      variations in infancy, thus contributing to the occurrence of hyperopia.

PMID- 23534255
TI  - [Association between age and chorioretinal hemodynamics in normal volunteers
      examined with laser speckle flowgraphy].
AB  - PURPOSE: To investigate the relationship between age and chorioretinal
      hemodynamics in normal volunteers examined with Laser speckle flowgraphy (LSFG
      NAVI). SUBJECTS AND METHODS: 107 eyes of 107 healthy volunteers aged from 21 to
      78 years old were included. Laser speckle flowgraphy measurements of relative
      blood velocity (mean blur rate: MBR), skewness in the wave of blood velocity
      (Skew) and blowout score (BOS), which indicates ease of blood flow, were obtained
      as parameters of chorioretinal hemodynamics. MBR and BOS were measured on the
      optic disc and macula, and BOS and Skew were measured in retinal arteries and
      veins. RESULTS: There was a negative correlation between age and MBR on the optic
      disc and macula. There was a negative correlation between age and BOS on the
      optic disc, macula, retinal arteries and retinal veins. CONCLUSION: There was a
      negative correlation between MBR, BOS and age in all measurement areas. MBR and
      BOS may serve as indexes for a new interpretation of fundus pathology including
      age-related arterial sclerosis.

PMID- 23534256
TI  - [Evaluation of chemokines in tears of patients with infectious keratitis].
AB  - PURPOSE: To investigate the chemokine profile in tears of patients with
      infectious keratitis. SUBJECTS AND METHODS: Subjects were 32 eyes of 16 patients
      with infectious keratitis and 5 eyes of 5 healthy volunteers as a control. The
      patients with infectious keratitis were classified into two groups of eyes: 10
      with bacterial keratitis and 6 with Acanthamoeba keratitis. Tear fluid was
      obtained from both eyes of the patients with infectious keratitis and from the
      right eyes of the control subjects using filter paper. Chemokine concentration
      (unit: Odu/mm2) and its profile in tears was analyzed using an antibody-array.
      RESULTS: In terms of chemokine profile in the bacterial keratitis group, the
      expression volume of interleukin-8 (IL-8) and monocyte chemoattractant protein-1
      (MCP-1) in the diseased eyes was significantly higher than in the healthy eyes (p
      < 0.05). The expression volume of mucosae-associated epithelial chemokines (MECs)
      in the diseased eyes of the bacterial keratitis group was significantly lower
      than in the healthy eyes of that group (p < 0.05). In the Acanthamoeba keratitis
      group, chemokines were not significantly increased in the diseased eyes compared
      with those in the healthy eyes. However, MCP-1 was increased in tears of the
      Acanthamoeba keratitis group. Regarding the chemokine ratio, the IL-8/MEC ratio
      in the diseased eyes of the Pseudomonas keratitis group and the MCP-1/IL-8 in the
      diseased eyes of the Acanthamoeba keratitis group showed a significantly high
      level (p < 0.05). CONCLUSION: We concluded that the analyses of the chemokine
      profile and chemokine ratio in the tears of infectious keratitis patients is
      useful as a clinical tear laboratory test to interpret the pathologic condition
      of infectious keratitis

PMID- 23534257
TI  - [Clinical investigation of the extrusion rate and other complications of the
      SuperEagle plug].
AB  - PURPOSE: Punctal occlusion using a silicone plug is reported as an effective way
      of treating severe dry eye. The purpose of this study is to investigate the
      migration, extrusion rate and complications of the SuperEagle plug (Eagle Vision)
      SUBJECTS AND METHODS: This study involved 148 puncta in 64 eyes of 85 patients
      (13 eyes of 10 men, 72 eyes of 54 women; mean age: 57.8 +/- 16.6 years [mean +/-
      standard deviation]) with severe dry eye who underwent punctual occlusion using a
      SuperEagle plug during the period of May 2009 to September 2010 at our dry eye
      clinic. We investigated the intracanalicular migration rate, extrusion rate,
      granulation rate, accumulation of soft whitish material and enlargement of
      punctum size after extrusion. RESULTS: The migration rate was 0%. The extrusion
      rate was 57.4% during follow up periods. The average time to extrusion was 92.4
      +/- 82.2 days, and the time until 50% of plugs were extruded was 154 days.
      Granulation was seen in 34.5% of the eyes. 52.9% of puncta that granulation was
      formed was completely occluded by granulation after extrusion. The accumulation
      of soft whitish material was not seen in any of the puncta. There was no
      significant change in the size of the puncta before insertion or after extrusion.
      CONCLUSION: The insertion of the SuperEagle plug was easy and without
      intracanalicular migration. Complete punctual occlusion by granulation after
      extrusion occurred.

PMID- 23534258
TI  - [Characterization and treatment of three cases with complications after frontalis
      suspension using autogenous fascia lata].
AB  - BACKGROUND: To report three cases of severe complications after frontalis
      suspension using autogenous fascia lata CASES: All three cases showed
      lagophthalmos and eyelash inversion after frontalis suspension using autogenous
      fascia lata. During surgery, we found that the tarsus was raised upwards and
      distorted by the fascia lata which had contracted and adhered to the surrounding
      tissue. We excised the adhesion of the fascia lata. In case 1, we transplanted
      the fat and perifascial areolar tissue under the cicatrized orbicularis. In cases
      2 and 3, we flattened the distorted tarsus with nylon mattress sutures. In case
      2, we added a frontalis suspension using Gore-Tex one year later. In case 3, we
      fixed Gore-Tex between the tarsus and the released fascia lata. CONCLUSIONS:
      Lagophthalmos and eyelash inversion due to contraction of the fascia lata may be
      complications of frontalis suspension using the fascia lata. Prolonged follow-up
      after the surgery is essential, and if such complications occur appropriate
      treatment is required.

PMID- 23534259
TI  - [Positive feedback is not fully effective in all situations].
AB  - This experimental study investigated how leader-member exchange (LMX) and
      positive feedback pertinent to the goal is related to subordinates'
      responsibility, assessment of their supervisors, and feeling of being implicitly
      scolded, to elaborate and confirm the findings of Bezuijen et al. (2010). We
      hypothesized that positive feedback pertinent to the goal would be more effective
      compared to unrelated feedback. Secondly, we hypothesized that this effect would
      be moderated by the quality of LMX. Undergraduate students (29 male, 51 female;
      20.4 +/- .63 yrs) participated as subordinates in an experiment consisting of two
      sessions. The results supported our hypotheses. We found that the positive
      feedback pertinent to the goal led to increased levels of responsibility. This
      effect was greater under high-quality LMX conditions, but was inhibited under low
      quality LMX conditions. In the high-quality LMX condition, subordinates who did
      not get any feedback decreased their responsibility, gave lower supervisor
      assessment ratings, and felt more strongly scolded than under conditions where
      they received feedback. We discussed the importance of the combination of the
      quality of the relationship and positive feedback related to the goal, and
      provided directions for future research.

PMID- 23534260
TI  - [Long-lasting implicit memory for unfamiliar faces revealed by an indirect
      recognition procedure].
AB  - We examined whether people can retain an implicit memory for unfamiliar faces
      over several weeks by using an indirect recognition procedure (Terasawa & Ohta,
      1993). The procedure was composed of two sessions with a long-term interval. Two
      experiments using different intervals--19 days (Experiment 1) and 7 weeks
      (Experiment 2)--were conducted. In each session, participants were presented with
      line drawings of faces and were asked to rate their preferences. The number of
      presentations varied for each condition in the first session. Participants were
      also asked to perform an unexpected recognition test for the faces presented
      after the rating task in the second session. Results from both experiments showed
      that the rates of correct and false recognition of faces increased significantly
      with the number of presentations in the first session. The findings indicate that
      long-lasting implicit memory can be formed for unfamiliar faces by incidental
      learning.

PMID- 23534261
TI  - [Decline of monocular contrast sensitivity during binocular fixation].
AB  - To investigate binocular single vision, we examined monocular contrast
      sensitivity during binocular fixation by changing the intervals between the
      beginning of fixation and a probe stimulus, within 10 seconds. Monocular contrast
      sensitivities were quite stable within 1s of the interval delay in both eyes, but
      they were reduced in either eye if the interval delay was more than 1s
      (Experiment 1). In Experiment 2, a similar stimulus was monocularly presented. In
      this case, decline of contrast sensitivity was not observed in either eye. In
      Experiment 3, when the stimulus was interrupted briefly before the probe
      presentation, the contrast sensitivity was recovered. These results suggest that
      after prolonged viewing the binocular system does not sustain either eye
      sensitivity equally unless there is interruption of the binocular stimulation.

PMID- 23534262
TI  - [Changes in academic motivation among elementary and junior high school
      students].
AB  - This study examined changes in academic motivation among elementary and junior
      high school students. Based on self-determination theory (Ryan & Deci, 2000a), we
      focused on changes in autonomous and controlled motivation. In Study 1, we
      examined inter-individual changes in academic motivation among 5th to 9th grade
      students (N = 1 572) through a cross-sectional study. In Study 2, we examined
      intra-individual changes in academic motivation among students (N = 128) who were
      in transition from elementary to junior high school through a longitudinal study.
      All participants completed the Academic Motivation Scale (Nishimura, Kawamura, &
      Sakurai, 2011) that measured autonomous and controlled motivation. The results
      revealed that autonomous motivation decreased in the students from elementary to
      junior high school, while controlled motivation increased during the same period.
      This is a unique finding because a prior study conducted in a Western culture
      suggested that both motivations decrease gradually in school.

PMID- 23534263
TI  - [Developmental Disorder Parenting Stressor Index (DDPSI): reliability and
      validity].
AB  - This study describes the development and evaluation of the Developmental Disorder
      Parenting Stressor Index (DDPSI). The DDPSI items were developed from a
      questionnaire survey of mothers (N = 255) of children with developmental
      disorders. A factor analysis identified four factors: (a) difficulty
      understanding the child and coping with the child's needs, (b) anxiety about the
      child's future and independence, (c) inadequate understanding of the child's
      disorder, and (d) conflicting emotions with regard to the child's disorder. These
      factors had high degrees of internal consistency. The concurrent validity of the
      DDPSI was examined. The DDPSI scores significantly correlated with the Stress
      Response Scale-18 and the Handicapped Child Parenting Stress Scale. The results
      of structural equation modeling analysis suggested that social support for the
      mothers mitigated the stressors' effect and reduced their psychological stress
      responses. The DDPSI is sufficiently reliable and valid to measure the stressors
      of parents of children with developmental disorders.

PMID- 23534264
TI  - [The effect of coping and appraisal for coping on mental health and later
      coping].
AB  - This study examined the effect of coping and appraisal for coping on mental
      health and later coping in two longitudinal studies. In Study 1 (Time 1: n = 342,
      Time 2: n = 367) investigated the influence of selected coping and coping for
      appraisal on mental health and assumed coping. In Study 2 (Time 1: n = 161, Time
      2: n = 154) investigated the influence of selected coping and coping for
      appraisal on mental health and later coping. The results indicated that coping
      and coping for appraisal affected mental health and later coping. However, the
      influence of the coping for appraisal was more limited than selected coping.

PMID- 23534265
TI  - [Facilitation and inhibition of insightful problem solving based on social
      comparison].
AB  - Intuitively, insight emerges unexpectedly. However, some previous views proposed
      that insight emerges with a high probability after people recognize their failure
      in solving a problem. In order to empirically investigate this failure-insight
      relationship, this study manipulated when participants recognized failure by
      using social comparison. It presumed that participants who had not yet solved the
      problem but knew others had already solved it would recognize that their
      currently adopted strategy was a failure; the timing of this was manipulated in
      the experiment. As expected, participants who were given a cover story regarding
      others' fast performance for the T-puzzle completed the same puzzle more
      successfully, as compared to those who were given a story of others' slow
      performance. The results suggest that the occurrence of insight was influenced by
      when participants recognized their failure. Providing social reality information
      (i.e., others' good/poor performance) might be a method to facilitate or inhibit
      insightful problem solving.

PMID- 23534266
TI  - [Effect of consensus on punitive behavior].
AB  - In addition to the cost of punishment, the fear that others would evaluate
      punishers negatively can be a major obstacle for resolving the second-order
      social dilemma or failure of providing sanctions useful for solving a social
      dilemma problem. In an experiment with 81 participants, we tested whether
      providing information that other participants were in favor of punishing non
      cooperators in a social dilemma situation would enhance cooperation in the second
      order dilemma (i.e., punishment of non-cooperators). Participants received
      feedback of three bogus "participants" choices in a four-person social dilemma,
      in which one bogus participant defected and two others cooperated, and then
      received a chance to punish the sole non-cooperator. The hypothesis was supported
      among those who were motivated to punish the non-cooperator. They punished the
      non-cooperator when they were informed that the other participants also wanted to
      punish the non-cooperator. The feedback information that the other participants
      wanted to punish the non-cooperator induced the participants who were not
      motivated to punish the non-cooperator to punish less.

PMID- 23534267
TI  - [Molecular-cellular mechanisms of light radiation and weak magnetic fields on the
      blood status and microcirculation system (at therapeutic doses) with using modern
      magnetolaser equipment (review of the literature)].
AB  - This review covers the molecular-cellular mechanisms of therapeutic action of
      light and magnetic field on blood components, blood vessels and the
      microcirculation system. Noted the role of the magnetic field as a trigger of
      vasodilation/vasoconstriction, depending on the initial vascular tone. Discussed
      the importance of NO-dependent effects of magnetic field on the microcirculatory
      response and angiogenesis.

PMID- 23534268
TI  - [Cardiovascular diseases as a problem of preventive medicine (review of the
      literature and our own research)].
AB  - In review the modern data about risk factors of developments of cardiovascular
      system diseases are summarized. The main attentions have given to modified
      factors. Among them the most essential are: smoking, the regular use of alcohol
      in the doses exceeding limit, low physical activity or excessive (professional)
      physical activity, irrational diet, an unbalance of microelements-nutrients,
      including the reduced content in a ration of manganese, ferrous, zinc, nickel,
      vanadium, selenium, copper, the smooth water with the reduced content of calcium,
      water with the excessive content of sodium, cadmium and lead. The negative
      influence of atmospheric factors, such as non-periodic oscillations of
      atmospheric pressure, high air humidity, temperature diversions, on a state of
      persons with meteorological sensitivity and cardiovascular diseases is marked.
      Exogenous factors of antihazard are generalized; on their bottom organizational
      principles and shapes of embodying of circulation system diseases prophylaxis are
      offered, which will to reduce a level of a case rate of the population on 30%,
      and frequency of relapses of cardiovascular infringements in 1, 6-2 times.

PMID- 23534269
TI  - [The effects of hypoxia on initiation and progression of cardiovascular disease
      in patients with chronic obstructive pulmonary disease].
AB  - Hypoxia accompanied chronic obstructive pulmonary disease leads to
      hypercoagulation, vessels' inflammation, imbalance of oxidative and antioxidative
      systems. These pathological changes cause arterial hypertension, corpulmonale,
      metabolism disturbance of the whole organism.

PMID- 23534270
TI  - [Vulval dermatitis: localized condition--serious problem].
AB  - An overview of the literature of the dermatitis of the vulva is presented. The
      etiology, epidemiology, clinical manifestations, diagnosis, pathological
      diagnosis, treatment, and prevention of contact, allergic-contact, atopic, and
      seborrheic dermatitis of the vulva are described in details. Lichen simplex
      chronicus is additionally described as complication of chronic itching
      dermatitis.

PMID- 23534271
TI  - [Importance of the hyperuricaemia, gout and gender nosological features in the
      activity of general practitioner - family doctor].
AB  - In this article there were analyzed gender data about features of hyperuricaemia
      and gout: women are much older at the onset of gout arthritis (one of main
      reasons, probably, makes menopause by itself), have more associated comorbid
      deseases as hypertension and kidney failure and drinks less alcoholic beverages.
      It was noticed, that typical localisation of the lesion on the first toe is less
      often in women, and women are more inclined to use diuretics among medical drugs.
      Abovementioned clinical features are of some importance for the broad activity of
      general practitioners - family doctors. Gender features of polyarthicular gout
      are not uniformed. Scientific researches confirmed possibility of the genetic
      basis of the uric acid metabolism, which influences some fenotypical features of
      the organism. Several genes are known for their influence on serum uric acid:
      PDZK1, GCKR, SLC2A9, ABCG2, LRRC16A, SLC17A3, SLC16A9 and SLC22A12. However,
      conclusions of the research works confirm the necessity of scientific
      clarification of the importance of different factors of gender differences.

PMID- 23534272
TI  - [Peculiarities of thyroid pathology in the childhood].
AB  - The paper deals with etiopathogenetic and clinical peculiarities, and also
      therapeutic methods during the pathological processes in the thyroid system in
      the childhood. The most common of these processes is the diffuse nontoxic goiter,
      which results in abnormality of metabolic processes regulation in the child's
      growing organism and often signals to the beginning of many thyropathies.

PMID- 23534273
TI  - [The role of humoral and cellular disturbances immunity in atherosclerosis and
      acute coronary syndrome].
AB  - Violations gumoralis and cellular immunity examine as one of anchormen of
      pathogenetic mechanisms development of ischemic heart trouble. These literatures
      over, that testifying to development of disbalance of subpopulations of T- and B
      lymphocitis, are brought, and also levels of immunoglobulin for patients with the
      stable and unstable flow of ischemic heart trouble.

PMID- 23534274
TI  - [Meta-analysis of randomized trials of antimicrobial drugs in the treatment of
      coronary heart disease].
AB  - The meta-analysis of 12 clinical research of application of antibiotics
      (azithromycin, roxithromycin clarithromycin, gatifloxacin) in 24 949 patients
      with coronary heart disease were carried out. The obtained results were shown
      that application of short courses of antibiotic therapy in patients with severe
      morphological changes in small coronary vessels were not enough effective.
      Contrariwise, long-term courses of antibiotic therapy could be effective in
      patients with initial lesions of blood vessels and presence of chronic
      infections.

PMID- 23534275
TI  - [Markers of active inflammation in patients with chronic bronchitis in
      combination with insulin resistance].
AB  - By us for diagnostics of activity of inflammatory process for patients by a
      chronic bronchitis (CB) in combination with insulintolerance the necessity of
      leadthrough of study of gemogramme and concentration of C-reactive protein was
      set for the whey of blood. Information of integral indexes of activity of
      inflammation (IAI) for patients with CB at presence of insulintolerance in the
      period of intensifying, and also and period of remission at majority inspected
      remained higher than norm in relation to healthy people. Quantitative
      determination of C-reactive protein in the whey of blood for the patients of CB
      with insulintolerance along with determination of level of leucocytes and indexes
      of leukogramme is the laboratory marker of activity of inflammation in the period
      of intensifying in the bronkholegochnoy system.

PMID- 23534276
TI  - [Survival for 48 months, survival predictors in patients with chronic heart
      failure of ischemic origin with systolic left ventricular dysfunction and
      preserved left ventricular ejection fraction].
AB  - 354 patients with chronic heart failure (CHF) of ischemic origin with systolic
      left ventricular dysfunction (SLVD) and 227 patients with preserved left
      ventricular ejection fraction (PLVEF) were examined. This study was aimed at the
      studying of comparative aspect of survival of patients with CHF and SLVD and with
      PLVEF for 48 months of observation, and the studying of nonsurvival predictors.
      Survival of patients with PLVEF is significantly better compared with survival of
      patients with SLVD for 48 months (66% and 42% respectively). The most informative
      predictors of 48 month in patients with SLVD were: uric acid level (OR = 3,17),
      end-systolic volume (OR = 2,71), hemoglobin level (OR = 2,64), creatinine level
      (OR = 2,36), end-dyastolic volume (OR = 2,49), index of end-systolic volume (OR =
      2,44). The most informative predictors in patients PLVEF were: cholesterol level
      (OR = 2,14) and distance of 6-minute walk (OR = 2,11).

PMID- 23534277
TI  - [Endoscopical features of precancer changes of the stomach in patients with
      chronic gastric erosions and biliary tract disease].
AB  - Frequency of the precancer changes of the stomach, diagnosed by using zoom
      endoscopy, NBI, chromoscopy, in the three groups of patients: with gastric
      erosions and biliary tract diseases, with gastric erosions and duodenal ulcer
      disease, with gastric erosions and chronic gastritis is compared in the article.
      It is shown, that patients with gastric erosions and biliary tract diseases are
      characterized by bigger spreading of precancer changes: atrophy, intestinal
      metaplasia with predominant smalluently intestine in gastric body, intestine
      metaplasia in antral part of the stomach is revealed more freq in these category
      of patients. A strong correlation between endoscopical and morphological methods
      of investigation was demonstrated.

PMID- 23534278
TI  - [Possibilities of magnetic-laser therapy in comprehensive treatment of patients
      with brain concussion in acute period].
AB  - The efficacy of magnetic-laser therapy used according to the method developed by
      us was studied in patients having the brain concussion (BC) in an acute period.
      The study was based on the dynamics of values of the evoked vestibular potentials
      and the disease clinical course. It was shown that following the magnetic-laser
      therapy in combination with traditional pharmacotherapy in BC acute period, the
      statistically significant positive changes were registered in the quantitative
      characteristics of the evoked vestibular brain potentials that correlated with
      the dynamics of the disease clinical course. The data obtained substantiate the
      possibility of using the magnetic-laser therapy in patients with a mild
      craniocereblal injury in an acute period.

PMID- 23534279
TI  - [Heterogeneity of chromosomal abnormalities in acute myeloid leukemia in
      different age groups children].
AB  - Characteristic of chromosomal abnormalities in bone marrow cells among 123
      children with acute myeloid leukemia were presented according five aging groups:
      I - up to 2 years, II - 2-5 years, III - 5-10 years, IV - 10-15 years, V - 15-18
      years. Normal karyotype wasn't found in group up to 2 years and in low presented
      in another groups (5, 9-10,3%). The highest frequency of chromosomal abnormality
      evolution in group up to 2 years was established (69,2%). The highest frequency
      of hyperdiploidy (47-50 chromosomes) in group 15-18 years (31%) was found. More
      often near-tetraploidy and pseudodiploidy clones were met in group 2-5 years (47%
      and 58,8%, respectively). Between structural types in all groups were
      predominated translocations and deletions. In group up to 2 years was prevalented
      translocations (61,5%), 2-18 years - deletions (64,7; 34,5; 45,7 and 41,4 %
      respectively). In group up to 2 years more often were met abnormalities
      chromosomes (Chr) 9, 11, 16 (in 30,8%), 2-5 years - Chr 16, 21 (in 29,4%), 5-10
      years - Chr 11 (24,1%), 8, 15, 17 (in 17,2%), 10-15 years - Chr 16 (40%) and 15
      18 years - Chr 8, 9, 15, 17 (in 17,2%).

PMID- 23534280
TI  - [Efficiency of enterosorbent White Coal in the treatment of the patients with
      chronic viral hepatitis C and its influence on lipoperoxidation markers and
      endogenous intoxication in blood of patients].
AB  - Efficiency of enterosorbent White Coal (aerosil) at the treatment of the patients
      with chronic viral hepatitis C (CVHC) was investigated. It was set that including
      of enterosorbent White Coal (aerosil) to the complex treatment of the patients
      with CVHC provided more fast liqudation clinical symptoms and provided
      archievment of clinical-biochemical remission and at pathogenetic plan--decrease
      of concentration "average molecules" and lipoperoxidation's products in the serum
      that testified about liqudation "metabolic intoxication" and oxidative stress
      syndromes.

PMID- 23534281
TI  - [Adaptol--verges of possible].
AB  - The analysis of the available in the modern literature researches allows us to
      consider Adaptol (active substance mebicarum) as drug with tranquilizing,
      nootropic and antioxidant activity that improves the adaptive capabilities of the
      body and certain organs and systems. However, described in some studies
      antianginal and antihyperlipidemic effect of the drug requires clarification of
      mechanisms of its occurrence: independent or by reducing the impact of stress
      influence.

PMID- 23534282
TI  - [Effect of fenugreek on the growth of different genesis tumors].
AB  - This paper deals with antitumor properties of a fenugreek (Trigonella Foenum
      Graecum L.) as to the different genesis tumors--the Ca755 mouse mammary carcinoma
      and the Guerin's carcinoma in rats. Fenugreek powder was shown to inhibit (25-40
      %) growth of certain tumors, decrease (27-63%) level of malone dialdehyde in
      liver, heart and kidney. Consumption of fenugreek was accompanied with decreased
      polyamines (spermine, spermidine, putrescine) content in tumor tissue. Inclusion
      of fenugreek to allowance was shown to improve certain blood value.

PMID- 23534283
TI  - [Creation and validation of the Ukrainian version of the Cardiff Acne Disability
      Index].
AB  - Original version of the Cardiff Acne Disability Index was translated into
      Ukrainian by two independent forward translators and then back-translated into
      English by two other independent translators. The probe technique for pre-testing
      was used. Retest reliability, discriminant and convergent validity and over time
      sensitivity were checked. The results of the Cardiff Acne Disability Index
      confirmed negative impact of acne on quality of life of Ukrainian patients.

PMID- 23534284
TI  - [Impact on the effectiveness of the special undeground constructions personnel of
      the professional content physical trainings].
AB  - The article presents data obtained in the study the degree of influence of
      physical training and vocational orientation of applied performance-career
      professionals who perform work as intended in the special underground facilities.
      The research, conducted with the assistance of civil and military professionals
      (mining engineers and military signalers) have shown that the lessons of
      professional-applied physical training have a positive effect on the performance
      of both types of specialists.

PMID- 23534285
TI  - [Outstanding domestic surgeon Vladimir Nikolayevich Shamov and his contribution
      to the development of the study of the blood transfusion (the 130th anniversary
      of his birth and the 50th anniversary of his death)].
AB  - The article is devoted to the memory of the outstanding domestic surgeon,
      Honoured Science Worker of the Ukrainian SSR, academician of the AMS of the USSR,
      who headed the Department of the Faculty Surgery of the Kharkov Medical Institute
      during 16 years (1923-1939), his name is associated with the development of the
      blood transfusion in our country.

PMID- 23534286
TI  - Sphingosine-1-phosphate: distribution, metabolism and role in the regulation of
      cellular functions.
AB  - The role of sphingosine-1-phosphate (S1P) in regulation of cellular functions and
      cell protection is reviewed. S1P, along with other sphingolipid metabolites, is
      believed to act as an intracellular second messenger and as an extracellular
      mediator molecule. S1P chemistry, production and metabolism are described.
      Cellular receptors for S1P and their tissue specificity are described. Platelets
      and erythrocytes have a crucial significance in blood transport of S1P. Hypoxic
      conditions induce an increase in S1P, which initiates a set of cytoprotective
      events via its cellular receptors. S1P involvement in regulation of cell
      migration, myogenesis, control of skeletal muscle function is described. It is
      shown that S1P balance disturbances may mediate pathological state. S1P system
      implication in regulation of the most important cellular functions allows
      considering it as a prospective remedial target.

PMID- 23534287
TI  - [Non-peptide furin inhibitors based on amidinohydrazones of diarylaldehydes].
AB  - A series of novel non-peptidic furin inhibitors containing amidinohydrazone
      moieties has been synthesized under interaction of dialdehydes, the derivatives
      of ethylene diethylvanillin ethers, with aminoguanidine bicarbonate. Two aryl
      cycles were bridged by 1,2-ethylene-, 1,4-buthylene- or 1,4-dimethylenebenzene
      group. The compounds have been found to inhibit furin. The antifurin activity was
      shown to grow with the increase of the length and/or hydrophobicity of the
      bridge. The most potent compound, containing in the bridge the lypophylic benzene
      cycle was found to inhibit the activity of furin with Ki = 0.51 microM.

PMID- 23534288
TI  - [The effect of potential-dependent potassium uptake on membrane potential in rat
      brain mitochondria].
AB  - The effect of potential-dependent potassium uptake on the transmembrane potential
      difference (DeltaPsi(m)) in rat brain mitochondria has been studied. It was shown
      that in potassium concentration range of 0-120 mM the potential-dependent K(+)
      uptake into matrix leads to the increase in respiration rate and mitochondrial
      depolarization. ATP-dependent potassium channel (K+(ATP)-channel) blockers,
      glibenclamide and 5-hydroxydecanoate, block approximately 35% of potential
      dependent potassium uptake in the brain mitochondria. It was shown that K+(ATP)
      channel blockage results in membrane repolarization by approximately 20% of
      control, which is consistent with experimental dependence of DeltaPsi(m) on the
      rate of potential-dependent potassium uptake. Obtained experimental data give the
      evidence that functional activity of K+(ATP)-channel is physiologically important
      in the regulation of membrane potential and energy-dependent processes in brain
      mitochondria.

PMID- 23534289
TI  - [Membranothropic properties of the urocanic acid].
AB  - The effects of urocanic acid (UA) on thermodynamic parameters of model
      dipalmitoylphosphatidylcholine (DPPC) lipid membrane have been studied by means
      of differential scanning calorimetry (DSC). The observed ordering effect of UA on
      the lipid bilayer is reflected in the increase in both the main phase transition
      temperature and cooperative unit size of the lipid membrane. Analysis of FTIR
      spectra suggests localization of UA molecules in the vicinity of the polar heads
      and carbonyl groups of DPPC due to electrostatic interactions and H-bonds. On the
      basis of experimental data obtained and geometry parameters of UA and DPPC
      molecules, some variants of the UA localization in DPPC bilayer were discussed.

PMID- 23534290
TI  - Biochemical effects of combined action of gamma-irradiation and paclitaxel on
      anaplastic thyroid cancer cells.
AB  - The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx),
      gamma-irradiation (IR) and their combination in undifferentiated thyroid cancer
      cells (ATC). IR activated common DNA damage-induced signaling and manifested
      certain mitogenic effect by inactivation of retinoblastoma protein (pRb). There
      was clear antagonism between Ptx and IR relative to cell cycle regulators--tumor
      suppressor p53, pRb, CHK2 and c-Abl as well as proapoptotic Bax expression, but
      combined action of both agents enhanced caspase-3 and, especially, caspase-8
      activation. The Ptx at low (1-25 nM) concentrations caused noticeable
      radioprotective effect. Thus, in ATC cells the ionizing radiation and Ptx
      exhibited competitive effects upon phosphorylation of cell cycle controllers:
      p53, pRb, CHK2, cAbl and expression of Bax. At the same time, the combined effect
      of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, caspases
      activation and survivin expression. The net effect of these events during the
      first 48-72 h of cells incubation can be considered as antiapoptotic--Ptx
      attenuated cytotoxic effect of IR.

PMID- 23534291
TI  - [Influence of poly(ADP-ribose) polymerase inhibitors on some parameters of
      oxidative stress in blood leukocytes of rats with experimental diabetes].
AB  - The study was undertaken to investigate the influence of specific inhibitors of
      poly(ADP-ribose)polymerase-1 (PARP-1), in particular nicotinamide and 1,5
      isoqinolinediol on white blood cells of rats with diabetes. Using the fluorescent
      probe 2',7'-dichlorodihydrofluorescein diacetate ROS production in leukocytes was
      asseced. It was found that the development of streptozotocin-induced diabetes was
      accompanied by an intensification of oxidative stress and a significant decrease
      in viability of blood leukocytes as compared to control animals. Administration
      of PARP-1 inhibitors prevented the development of oxidative stress in leukocytes
      and increased their viability. It was shown a reduction of superoxide dismutase
      activity in serum in diabetes. Investigated PARP-1 inhibitors had no effect on
      the activity of superoxide dismutase and glucose levels in the blood. The
      findings suggest the intensification of oxidative stress in leukocytes of
      diabetic animals and the ability of nicotinamide and 1,5-isoqinolinediol to
      prevent its development depending on the features of their structure.

PMID- 23534292
TI  - [The glutathione system in the blood of rats and morphological changes of the
      pancreas under experimental acute and chronic pancreatitis].
AB  - In experiment on laboratory rats the models of acute and chronic pancreatitis
      were developed to study the changes of lipoperoxidation-antioxidant protection
      system depending on morphological changes of the pancreas. The acute and chronic
      pancreatitis is accompanied with intensification of lipoperoxidation and gradual
      inhibition of antioxidant system due to development of subsequent chronization of
      the pathological process.

PMID- 23534293
TI  - [Effect of anticonvulsants on the nitric oxide system].
AB  - The effect of phenobarbital, carbamazepine, valproate sodium, depakine,
      topiramate and lamotrigine on the content of NO and NO-synthase activity in white
      rat brain tissues has been studied. It was established that the action of
      carbamazepine, valproate sodium, topiramate and lamotrigine decreases the
      activity of NO-synthase and the level of NO in the brain tissues. The amount of
      NO does not change while NO-synthase activity increases with the introduction of
      phenobarbital. The involvement of nitric oxide in the mechanism of action of the
      studied anticonvulsant drugs is discussed.

PMID- 23534294
TI  - [Infant nutrition-experiences, new trends and recommendations].

PMID- 23534295
TI  - Anthropometric indicators of mass and distribution of adipose tissue in the
      assessment of cardiovascular and diabetes risk in women.
AB  - INTRODUCTION: From the clinical and epidemiological point of view it is very
      important to define easily measurable and simple anthropometric parameters of
      mass and distribution of adipose tissue that will also be good predictors of
      future complications of obesity. The aim of our study was to correlate
      anthropometric indicators of mass and distribution of adipose tissue with the
      risk of developing cardiovascular diseases and diabetes. MATERIAL AND METHODS:
      The study group consisted of 155 women aged 45.4 +/- 13.04y. The anthropometric
      measurements were performed in order to assess adipose tissue mass and its
      specific distribution. The 10-year risk of developing cardiovascular diseases was
      assessed by using two score-systems: Framingham and Prospective Cardiovascular
      Munster Study while the 10-year risk of development of diabetes was assessed by
      QDScore system. RESULTS: According to our results, the waist-to-stature ratio was
      the best predictor of cardiovascular and diabetes risk (r = 0.617-0.780; AUC =
      0.872). The estimated cut-off value for the waist-to-stature ratio in
      cardiovascular and diabetes risk prediction was 0.486. Apart from the waist-to
      stature ratio, the body mass index, body fat mass, waist circumference and
      indicators of upper extremity adiposity also correlated strongly with the
      assessed risk. The anthropometric indicators of lower body adiposity had no
      significant diagnostic values. CONCLUSION: The waist-to-stature ratio is the best
      anthropometric indicator of cardiovascular and diabetes risk.

PMID- 23534296
TI  - [Evaluation of disease frequency in the first line relatives of patients
      suffering from schizophrenia related to gender and diagnostic categories].
AB  - INTRODUCTION: Schizophrenia represents the most severe mental disorder. The aim
      of this study was to determine the frequency of disease in the first line
      relatives of patients suffering from schizophrenia related to gender differences
      and various subtypes. MATERIAL AND METHODS: The study included 453 subjects (121
      patients suffering from schizophrenia - 52.1% males and 47.9% females and 332
      first line relatives of the patients - 47.2% males and 52.7% females during a
      five year period, mostly in the region of Sarajevo. RESULTS: According to the
      analysis of disease frequency related to the kinship, the disease developed more
      frequently in mothers (8.3%) and sisters (7.8%) than in fathers (6.9) and
      brothers (7.1%) of the patients suffering from paranoid schizophrenia. In the
      group of disorganized schizophrenia, only mothers were found (4.2%), whereas the
      statistical difference in the group of affected brothers and sisters was
      significant, the percentage being 9.7% and 15.3%, respectively. There was a
      statistically significant difference in gender (p < 0.05) between the group of
      parents and siblings regarding the frequency of schizophrenia. DISCUSSION: The
      proof of participation of genetic factors in etiology supports the assumption on
      genetic nature of familial aggregation of schizophrenia. Our results completely
      match those of studies which analyzed the frequency of disease regarding
      inheritance (gender distribution and various subtypes). CONCLUSION: Investigation
      points to the common epidemiological criteria regarding the frequency of
      schizophrenic psychosis. Genetic predisposition could be also a demonstrator of
      the disease course and outcome, which should enable better understanding of the
      etiology of this disease.

PMID- 23534297
TI  - [Cardiovascular disease risk factors in patients with non-alcoholic fatty liver
      disease].
AB  - INTRODUCTION: Clinical, epidemiological and biochemical studies strongly support
      the concept that the non-alcoholic fatty liver disease is a hepatic manifestation
      of the metabolic syndrome. Insulin resistance is a common factor connecting
      obesity, diabetes, hypertension and dyslipidemia with fatty liver and the
      progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and
      hepatocellular carcinoma. Since identification of cardiovascular risk factors is
      the first step in their prevention, the aim of this study was to analyze the
      prevalence of some risk factors in patients with fatty liver. MATERIAL AND
      METHODS: The study included 130 patients who met metabolic syndrome criteria;
      their demographic and anthropometric characteristics were analyzed and some
      clinical characteristics were determined, such as smoking habit, arterial
      pressure and alcohol intake. Routine biochemical analyses were carried out by a
      standard laboratory procedure. Hepatic steatosis was detected by the abdominal
      ultrasound. Modified criteria of the National Cholesterol Education Program Adult
      Treatment Panel III were used to describe the metabolic syndrome. RESULTS: The
      study group consisted of 72 subjects (55.38%), who had been found by ultrasound
      to have fatty liver, whereas the control group included 58 respondents (44.62%)
      without pathological ultrasound findings. Differences in the number of fatty
      liver were highly statistically significant between the groups. The values of
      body mass index (33.56 +/- 6.05 vs 30.56 +/- 4.23 kg/m2; p = 0.001), glucose
      (6.23 +/- 0.95 vs 5.76 +/- 0.88 mmol/l; p < 0.01) and cholesterol (6.66 +/- 1.30
      vs 6.23 +/- 0.95; p < 0.05) were significantly higher in the patients with fatty
      liver than in those without fatty liver. CONCLUSION: Our results indicate that
      the patients from the study group had a high percentage of cardiovascular risk
      factors.

PMID- 23534298
TI  - [Impact of hearing impairment on quality of life of adolescents].
AB  - INTRODUCTION: Hearing impairment, as a type of sensory disability affects the
      quality of life of adolescents. The aim of this study was to determine whether
      the quality of life of adolescents with hearing impairments was different from
      the quality of life of adolescents without disabilities, and to examine the
      correlation between self--reported quality of life and proxy--report by their
      parents. MATERIALS AND METHODS: The study included 52 adolescents with hearing
      impairment and 122 adolescents without developmental disabilities, aged from 13
      to 18 years and their parents. Data were collected by a standardized
      questionnaire, the PedsQL 4.0 Generic Core Scale. The survey was conducted during
      May and June 2011 in 6 schools in Novi Sad and Belgrade. RESULTS: Adolescents
      with hearing impairment and their parents reported lower scores on all scales of
      questionnaire. The average score of physical health was 77.58; p < 0.001
      (adolescents), and 75; p = 0,006 (parents); on psycho-social summary scale 75.35;
      p = 0.025 (adolescents), and 73.37; p = 0.02 (parents). On the overall scale, the
      adolescents scored 76.13; p < 0.001, and parents reported 73.93; p < 0.001. The
      parents assessed the quality of life lower than their children. On the total
      summary scale, a moderate agreement (r = 0.51) was found between self- report and
      proxy- report. CONCLUSION: Hearing loss affects all aspects of the quality of
      life of adolescents. A multidisciplinary approach is required in order to provide
      better conditions for functioning of these children and improve their quality of
      life.

PMID- 23534299
TI  - Analysis of associated diseases in patients with acute critical lower limb
      ischemia.
AB  - INTRODUCTION: Acute critical lower limb ischemia refers to the state of severely
      impaired vitality of lower limbs due to acute occlusion of arterial blood vessel
      by a thrombus or emboli. Surgical revascularization in the first 6-12 hours after
      the onset of symptoms gives the best results. However, a high mortality rate and
      probability of limb loss make this problem more debatable, and can be related
      with associated diseases. MATERIAL AND METHODS: This research included 95
      patients who had been operated within the first 12 hours after the onset of
      symptoms of critical limb ischemia We collected the following data: age and sex
      of patients, etiology of limb ischemia, type of operation, associated diseases
      and outcome of treatment. RESULTS AND DISCUSSION: Most of the patients were 70 to
      80 years old, both sexes being equally represented. There was significantly more
      arterial embolism (70%) than thrombosis on the prior arterial lesion. Most of the
      embolizations were treated with Fogarty balloon catheter embolectomy (98%);
      however, a great number ofarterial thrombosis demanded more complex "inflow" and
      "outflow" ensuring procedures such as thromboendarterectomy and bypass (33%). The
      performed surgical procedures showed no statistical differences when final
      outcome was analyzed. Amputation had to be performed in about 3% of the patients
      and all of them were diabetics. Mortality rate in this research was 10.5% and
      7/10 with this outcome had severe form of chronic myocardiopathy and metabolic
      decompensation. CONCLUSION: Acute critical lower limb ischemia should be treated
      surgically as soon as possible. Negative outcomes are associated with comorbidity
      and general condition of the patient.

PMID- 23534300
TI  - Early detection of asthma and chronic obstructive pulmonary disease in primary
      care patients.
AB  - INTRODUCTION: Asthma and chronic obstructive pulmonary disease are often
      unrecognized and undertreated. The aim of this study was to describe the
      frequency of chronic obstructive pulmonary disease and asthma in primary care
      patients in Serbia, and to examine the agreement between general practitioners
      and pulmonologists on the diagnosis of chronic obstructive pulmonary disease and
      asthma. MATERIAL AND METHODS: In this multicenter observational study, the
      general practitioners identified eligible patients from October 2009 to June
      2010. The study included all adult patients with respiratory symptoms and/or
      smoking history based on structured interview. The patients were referred to a
      pulmonologist and underwent a diagnostic work-up, including spirometry. RESULTS:
      There were 2074 patients, 38.4% men, their mean age being 54 +/- 15.5 years. The
      patients were mostly current (40.3%) or ex-smokers (27.4%). The common symptoms
      included shortness of breath (84.9%), cough (79.1%) and wheezing (64.3%). The
      diagnosis of chronic obstructive pulmonary disease was confirmed by
      pulmonologists in 454 (21.9%) and asthma in 455 (21.9%) patients. The chronic
      obstructive pulmonary disease was newly diagnosed in 226 (10.9%) and asthma in
      269 (13%) of the cases. There was a moderate agreement between the pulmonologists
      and general practitioners on the diagnosis of chronic obstructive pulmonary
      disease (kappa 0.41, 95% CI 0.36-0.46) and asthma (kappa 0.42, 95% CI 0.37
      0.465). CONCLUSION: A significant number of patients seen in the general
      practitioner's office were diagnosed with chronic obstructive pulmonary disease
      or asthma and half of them represent new cases. A substantial proportion of
      patients referred to a pulmonologist by primary care physicians have been
      misdiagnosed.

PMID- 23534301
TI  - Pathophysiology of migraine--from molecular to personalized medicine.
AB  - INTRODUCTION: Understanding of migraine pathophysiology has substantially
      improved over the last two decades. As a result, migraine is now mainly
      considered to be a disorder of the brain, rather than one of the vasculature or
      the meninges. PATHOPHYSIOLOGY: Although it remains speculative how exactly they
      relate to each other, the following three processes are important in migraine: 1.
      Cortical spreading depression is a wave of intense depolarization, it starts in
      the occipital lobe, propagates through the brain and is followed by a period of
      suppressed activity. 2. Activation of the trigemonovascular system causes the
      release of neuropeptides (e.g. calcitonin gene-related peptide, substance P) from
      the peripheral trigeminal nerve endings. These neuropeptides are thought to play
      a role in causing and maintaing headache. 3. Sensitization of peripheral and
      central brain areas, it is thought that pulsating quality of migraine headache is
      caused by a process of peripheral sensitization. Cutaneous allodynia is a marker
      of central sensitization. LINK BETWEEN AURA AND HEADACHE: The view that the aura
      is caused by cortical spreading depression has become generally accepted, and the
      same is true for the view that activation of the trigemonovascular system
      underlies migraine headache. However, the relationship between the aura and the
      activation of the trigemonovascular system and the start of headache remains
      elusive. GENETICS OF MIGRAINE: One of the most important aspects of the
      pathophysiology of migraine is the hereditary nature of the disorder. CONCLUSION:
      Identification of polymorphisms and genetic biomarkers should help us to
      understand migraine pathophysiology better and thus enable the development of
      specific, effective "individually-tailored treatment" for each particular
      migraine patient (personalized medicine).

PMID- 23534302
TI  - [The type and screen method of blood requisition in General Hospital Zrenjanin].
AB  - INTRODUCTION: The basic principle of patient's chemotherapy is that its
      performance is rational, safe and of high quality. In order to rationalize the
      whole process, the Transfusiology Committee has decided to introduce the Type and
      Screen method (typifying of blood types and screening of antibodies) in pre
      transfusion testing in General Hospital "Dorde Joanovic" in Zrenjanin. The method
      represents the strategy of clear defining and standardizing of the blood
      requirement process during various elective surgical operations. MATERIAL AND
      METHODS: In order to record chemotherapy efficiency, the following parameters are
      used: crossmatch/ transfusion ratio, transfusion probability and transfusion
      index. These parameters give us exact data that enable us to understand whether
      adequate blood requisition is made. The aforementioned parameters are followed
      both before and after the introduction of the Type and Screen method. RESULTS.
      Since the Type and Screen method was introduced, the percentage of the reserved
      blood has been used more efficiently, i.e. the number of patients taken off the
      reservations list has been reduced, which can be seen from the correction of
      transfusion probability from 44.96 to 61.28 and transfusion index from 0.36 to
      0.60. Crossmatch/transfusion ratio has changed from 2.33 to 1.81 after the Type
      and Screen method was introduced, which implies that deplasmatised erythrocytes
      reservation has been rationalized. CONCLUSION: By following the above parameters,
      data have been obtained which point to the rationalization in blood reservations,
      resulting in greater number of blood units available. The "Type and Screen" list
      has become a standard in our hospital when it comes to blood products
      requisition.

PMID- 23534303
TI  - Heart surgery in patients on chronic dialysis.
AB  - INTRODUCTION: Patients on dialysis for end-stage renal failure are subjected to
      cardiac surgery with increasing frequency. End-stage renal failure is known to be
      an important risk factor for complications of cardiac operations performed with
      cardiopulmonary bypass. The aim of this study was to determine the impact of
      preoperative clinical status and operative variables on perioperative morbidity
      and mortality in hemodialysis-dependent patients subjected to a cardiac surgery.
      MATERIAL AND METHODS: The following operative variables were examined: urgency,
      type and duration of surgery and duration of extracorporeal circulation. The
      study is a retrospective analysis of consecutive patients with end-stage renal
      failure dependent on maintenance hemodialysis who underwent cardiac surgery
      during four years. RESULTS: The study included 46 patients. Operations performed
      included isolated coronary artery bypass grafting (CABG, n = 24), valve surgery
      alone (n = 6), and combined valve surgery or coronary artery bypass grafting and
      valve surgery (n = 16). The perioperative mortality rate was 13% with four fatal
      outcomes in patients who had undergone combined cardiac surgery. We found age >
      70 years, preoperative New York Heart Association class IV, preoperative anemia,
      combined surgery and emergent surgery to be associated with a higher relative
      risk for perioperative death. CONCLUSION: Patients on dialysis have an increased
      morbidity and mortality following cardiac surgery; however, we believe that end
      stage renal failure should not be regarded as a contraindication to cardiac
      surgery or cardiopulmonary bypass.

PMID- 23534304
TI  - [Oral health related knowledge and health behavior of parents and school
      children].
AB  - INTRODUCTION: The family provides the background for developing behaviors,
      attitudes and knowledge related to oral health of children. The aim of this study
      was to compare oral health behavior of parents and their children and to asses
      the impact of parental behavior on children's oral health. MATERIAL AND METHODS:
      This cross-sectional study included 99 parent--child pairs (12 to 15 years old).
      Data on oral health behavior, knowledge and attitudes regarding oral hygiene,
      fluorides and nutrition of parents and their children were collected by
      questionnaires. The parental dental health was assessed according to self
      reported data on tooth loss and prosthodontic rehabilitation, while the dental
      status of children was determined by clinical examination. RESULTS: The parents
      reported the use of dental floss (p < 0.001) and mouth rinses (p < 0.05) more
      often than their children and they had better knowledge on fluorides.
      Approximately one third of parents thought they should not control sugar
      consumption of their child. There was a statistically significant correlation
      between parental oral hygiene and their habit to control the child in brushing
      with the child's oral health status. CONCLUSION: Oral health education activities
      directed towards the prevention of risk factors for developing caries should
      involve both parents and their children, because parental behavior is a
      significant predictor of children's oral health.

PMID- 23534305
TI  - [Immunized pregnant woman with rare Rh fenotype--case report].
AB  - INTRODUCTION: Rh blood group system is one of the most polymorphic systems of
      human blood and consists of 50 antigens. Antigen D is the most important antigen
      in the Rh system and next to ABO, is the most clinically significant in
      transfusion medicine. The aim of this paper was to present a case of a rare Rh
      phenotype ccDEE in an immunized pregnant woman, whose fourth pregnancy ended with
      birth of a female newborn infant with hemolytic disease of the lower level. CASE
      REPORT: The history of a 42-year-old pregnant woman stated that she had had four
      pregnancies. She was transfused with 1500 ml of whole blood, three units of
      packed red cells and two units of fresh frozen plasma. Due to her high-risk
      pregnancy she was referred to the Clinic of Gynecology and Obstetrics in Novi
      Sad. Blood sample was tested in the Department of Prenatal Care of the Institute
      for Blood Transfusion Vojvodina. ABO and Rh were tested, antibody screening was
      done by indirect antiglobulin test and the detected antibodies were identified by
      gel technology. The results of testing were: O RhD positive, Rh phenotype ccDEE,
      positive screening for red blood cells antibodies by indirect antiglobulin test,
      alo anti-e antibody. According to the literature data, it is a very rare Rh
      phenotype whose incidence in the population ranges from 0.34% to 1.99%. The
      compatible blood products for the patient and her newborn were searched for on
      the basis of the immunoserology tests. CONCLUSION: Two major problems within
      transfusion medicine have emerged in our case: the problem of immunization of
      pregnant woman with a rare blood type and the problem of finding compatible
      blood. Health care of pregnant women can be improved by following pregnancies
      according to the national antenatal testing algorithm and better teamwork of
      gynecologists and transfusions.

PMID- 23534306
TI  - [The importance of cytology in diagnosing rare breast carcinoma--two case
      reports].
AB  - INTRODUCTION: This paper presents two cases of very rare tumors of breast: breast
      sebaceos carcinoma, which has rarely been described in medical literature, and
      breast carcinosarcoma. Morphological characteristics and biological behavior of
      sebaceos carcinoma are still rather vague. Carcinosarcoma of the breast is a rare
      malignancy with distinct cell lines described as a breast carcinoma of ductal
      type with a sarcoma-like component. CASE REPORT: The first presented case is a 73
      year-old female referred to our hospital in January 2008 with tumor of the right
      breast in the upper outer region of the breast and enlarged lymph nodes in the
      right axillary region. The second presented case is a 51-year-old female with
      carcinosarcoma, also a very rare primary breast tumor. She was admitted to our
      hospital in June 2011 with history of lump in the upper and lower outer quadrant
      of the left breast. In both cases, biopsy of tumor tissue was carried out with a
      thin needle, i.e. the aspiration cytology was applied as a diagnostic method, and
      during the operation the fast diagnostics of frozen sections and cytologic
      diagnostics were done. Although this methodology is important in diagnosis, in
      both cases it showed certain limitations in diagnosing such rare tumors. The
      final diagnosis was made after carefully synthesizing the histological findings
      and immunohistochemical phenotype. CONCLUSION: An accurate classification of
      breast tumors on cytological preparations is not possible in case of poorly
      differentiated and rare tumors. A careful and accurate classification of these
      tumors is necessary.

PMID- 23534307
TI  - [Reminiscence on the municipal out-of-hospital maternity unit and the motherhood
      home in Novi Sad].
AB  - INTRODUCTION: In the mid-twentieth century, the health care of women and children
      was inadequate in the post-war Yugoslavia, including the city of Novi Sad, due to
      the severe post-war reality: poverty in the devastated country, shortage of all
      commodities and services and especially of medical supplies, equipment and
      educated staff. OUT-OF-HOSPITAL MATERNITY UNIT: One of the serious problems was
      parturition at home and morbidity and mortality of the newborns and women. Soon
      after the World War II the action programme of improving the women's health was
      realized on the state level by establishing out-of-hospital maternity units but
      under the expert supervision. The Maternity unit at 30 Ljudevita Gaja Street in
      Novi Sad played a great role in providing skilled birth attendance at mainly
      normal deliveries. With a minimal number of medical staff and modest medical
      equipment, about 2000 healthy babies were born in this house. MOTHERHOOD HOME:
      After 5 years of functioning in that way, this unit was transformed into the
      Motherhood Home and became a social and medical institution for pregnant women
      and new mothers. Regardless of the redefined organization concept the curative
      and preventive health care as well as women and children social protection
      programmes were provided successfully for the next 12 years. Although the
      Motherhood Home was moved into the Women Health Centre of Novi Sad and later into
      the former Maternity Hospital in Sremski Karlovci, its great importance for women
      and children's health care remained unchanged. In 1979 the overall social
      situation and mostly economic issues led to its closing. EPILOGUE: The house in
      Gajeva Street is now used as the municipality office. However, this house with
      its story recommends itself to become a house for a special social function, such
      as a museum of medical history of Novi Sad. A small investment could make it
      possible to collect, preserve and display the valuable records of our past, which
      is something we do owe to the generations to come.

PMID- 23534308
TI  - [Morbidity structure among prematurely born babies of the same gestational age
      from single and twin pregnancies].
AB  - INTRODUCTION: Premature infants, born before 37 completed weeks of gestation,
      belong to the category of at-risk children. They have a lower survival rate due
      to complex multifactorial diseases such as respiratory distress syndrome,
      nosocomial sepsis, necrotizing enterocolitis, intracranial pathologies (bleeding,
      ischemia, maldevelopment), retinopathy of prematurity, and bronchopulmonary
      dysplasia which threaten survival and optimal neurodevelopment. Multiple
      pregnancies are more often delivered before the due date. Our objective was to
      determine the morbidity structure among prematurely born twins compared to
      singletons of the same gestational age. MATERIAL AND METHODS: The analysis
      included 60 prematurely born children (30 preterm twins and 30 singletons) who
      had been diagnosed with one or more diseases: respiratory distress syndrome,
      intraventricular hemorrhage, retinopathy, icterus, septicaemia, and other, with
      the exception of general infections. RESULTS: The most common diagnosis of
      preterm twins and singletons was hyperbilirubinaemia (83.3%) and respiratory
      distress syndrome (78.3%). Infections follow with 25% and intracranial hemorrhage
      with 21%. CONCLUSION: According to statistical analyses, there is no significant
      difference in incidence of morbidity among prematurely born singletons and
      preterm twins.

PMID- 23534309
TI  - [Evaluation of the practice of transfusion in the anemia in preterm infants].
AB  - The early anemia in preterm infants, usually implies as a remedy, the use of
      erythrocyte transfusions indicated according to transfusion criteria which are
      variable from one neonatal center to another. OBJECTIVE: To evaluate our practice
      of transfusions concerning the anemia in preterm infants. METHODS: A descriptive
      study on 113 preterm infants whose gestational age is < 37 weeks and who were
      hospitalised in Neonatal Service at the Infants Hospital at Rabat during the year
      2006, by recording the gestational age, the weight at birth, the rate of
      haemoglobin and hematocrit at the first admission of the infant and before his
      first blood transfusion and finally the clinical and biological indications. In
      order to analyse the criteria of blood transfusion, we have compared between two
      groups: a group A of 65 transfused preterm infants and a group B of 48 non
      transfused with the test of Chi2 and t Student at threshold of P < 0,005.
      RESULTS: The medium gestational age was that of 33 weeks and the medium weight at
      birth was 1.672 g. 57,5% of preterm infants were transfused. The preterm babies
      who has received transfusion compared to those who have not, are significantly
      more preterm, their weight at birth is weak and the time of hospitalisation is
      longer, having had more nosocomial infections, postnatal bleeding and their
      haemoglobin and hematocrit rate at birth is lower (P < 0,001). 41,5% of
      transfused infants had presented clinical signs of anemia and had been transfused
      one week earlier than asymptomatic infants and had elevated rates of haemoglobin
      and hematocrit (P < 0,005). CONCLUSION: The use of blood transfusion is frequent
      in our context and implies preventive measures to reduce it.

PMID- 23534310
TI  - [The use of lasers in dermatology].
AB  - Albert Einstein is undoubtedly the father of lasers. But it is not until 1964
      that the first dermatological lasers were introduced. The Nd-YAG laser, the CO2
      laser were developed by Kumar Patel. In a 40 year period lasers not only were
      diversified but have also become safer and miniaturized. This article hopes to
      strengthen general practionners' and specialist's knowledge of the different
      categories of available lasers. The most frequently used ones are ablative lasers
      (CO2-Erbium), vascular lasers (Nd-YAG, KTP, pulsed dye laser) and the pigment
      lasers (Q-Switched Nd-YAG, Alexandrite). A description of these lasers and their
      indications in dermatology will be discussed.

PMID- 23534311
TI  - [Continuous sedation: practical and ethical aspects].
AB  - Continuous sedation is an acknowledged medical practice in the management of
      refractory symptoms at the end of life. Guidelines and recommendations have been
      proposed in palliative care. This paper presents the state-of-the-art
      (definitions, indications, technical aspects) on continuous sedation followed by
      an ethical reflection essentially based on the "double effect" principle, on the
      impact on life expectancy and the assimilation of continuous sedation as a
      "natural death". Distinction between continuous sedation and legal euthanasia is
      clarified.

PMID- 23534312
TI  - [Chronic pelvic pain syndrome].
AB  - Chronic prostatitis are caused by infection in 5-10% of cases and other entities
      are called "chronic pelvic pain syndrome". The current classifications are based
      on the presence or absence of inflammation or infection in the prostatic
      secretions. The new concept of clinical phenotype "UPOINT" offers six domains
      (urinary, psychosocial, organ-specific, infectious, neurological, systemic and
      related to muscle tension) and can guide treatment according to the phenotype
      expressed by the patient. The therapeutic approach is based on the first use of
      antibiotics with or without alpha-blockers. Depending on clinical response,
      supportive treatment should be considered. The role of psychological support
      remains essential. Few studies of effectiveness of a level 1 of evidence are
      available and the chronic pelvic pain syndrome remains a controversial entity in
      the etiology whose treatments are empirical. The authors review current knowledge
      on the best treatment suited to the "chronic prostatitis".

PMID- 23534313
TI  - [Orthogeriatrics: supportive evidence for the process].
AB  - Incidence of hip fractures increases dramatically in the aging population leading
      to increased admissions of frail old patients. The proof of concept of the
      efficacy of comprehensive geriatric assessment exists for non orthopaedic old
      subjects. This review identifies innovative models of care for the management of
      older adults with hip fracture, distinguished mainly on the basis of the role of
      the healthcare professionals involved in the care and their responsabilities. The
      managements are heterogeneous and the models are often combined. The choice to
      implement a model should depend of his level of evidence, the existing resources,
      and the willingness of both orthopaedic, and geriatric teams. The heterogeneity
      of the models, of the nature of interventions, of the populations and of the
      outcomes is challenging to undertake meta-analysis in order to choice one
      "universal" model. However there is a tendency to better overall outcomes in
      patient receiving co managed care: subjects admitted for hip fracture are often
      frail adults requiring a comprehensive management in order to identify and treat
      geriatric syndromes.

PMID- 23534314
TI  - [Ignored homicides].
AB  - Forensic medicine is a fundamental science for a good evolution of the law and a
      serious protection of citizens. This science is also inextricably linked to
      public health. As basic discipline, we consider useful to revisit homicides which
      escape the investigators'sagacity and especially to know the reasons of this
      missing. Forensic high quality depends on respect of the crime scene, through
      specialized training and above all the recognition of this crucial discipline in
      our contemporary society.

PMID- 23534315
TI  - [Bernard van den Corput, a Belgian doctor of the XIXth century].
AB  - Issued from a patrician family, Bernard van den Corput was professor of therapy
      at the Medical School from the Universite libre de Bruxelles. He accomplished a
      very brilliant academic career and was member of many Belgian and foreign
      scientific associations. He is the author of a very large number of publications,
      not only in the field of medicine, and his strong personality is at the origin of
      many exceptional events.

PMID- 23534316
TI  - Systematic reviews in dental research. A guideline.
AB  - BACKGROUND: A systematic review aims to combine outcome data from published
      studies in a population. It is based on a number of steps and although there are
      numerous advantages in systematic review studies, dentists have been finding
      difficulties in performing them. OBJECTIVE: Taking into account the
      misconceptions and difficulties in conducting this kind of study, this article
      aims to guide readers for understanding, performing, and interpreting
      comprehensive systematic reviews in dental research.

PMID- 23534317
TI  - Measurement and assessment of pain in children--a review.
AB  - Pain is a common experience during childhood. Despite the magnitude of effects
      that pain can have on a child, it is often inadequately assessed and treated.
      Numerous myths, insufficient knowledge among caregivers, and inadequate
      application of knowledge contribute to the lack of effective management. The
      pediatric pain experience involves the interaction of physiologic, psychologic,
      behavioral, developmental, and situational factors. Pain is an inherently
      subjective multifactorial experience and should be assessed and treated as such.
      Pediatric Dentists are responsible for eliminating or assuaging pain and
      suffering in children when possible. To accomplish this, we need to expand our
      knowledge, use appropriate assessment tools and techniques, anticipate painful
      experiences and intervene accordingly. As an assessment of pain which constitutes
      the foundation for all pain treatment, developing valid measures is both a
      clinical and research challenge. Clinicians and researchers should select
      measures with full knowledge of their psychometric strengths and weakness, as
      well as in keeping with their explicit conceptual model of pain. The purpose of
      this paper is to address potential sources of pain measurement, and responses to
      pain control and distractions based on the pediatric developmental stages.

PMID- 23534318
TI  - Clinical and radiographic outcomes of pulpotomized primary molars treated with
      white or gray mineral trioxide aggregate and ferric sulfate--long-term follow-up.
AB  - AIM: To compare the long-term clinical and radiographic outcomes of pulpotomies
      in primary molars performed with white or gray Mineral Trioxide Aggregate (MTA)
      in combination with ferric sulfate (FS), when one package of MTA is used for
      multiple treatments. DESIGN: Sixty eight children with 86 vital carious primary
      molars underwent pulpotomy with FS, and grey or white MTA. One package of MTA was
      used for 7-8 treatments. Clinical and radiographic evaluation was performed
      before and 6 to 47 months after treatment. RESULTS: Success rates were similar
      for pulpotomies performed with white (60-teeth) and grey MTA (16 teeth) (p >
      0.05), and for those performed with the addition of FS to white or gray MTA when
      one package of MTA was used for multiple pulpotomies compared to one package of
      MTA alone. CONCLUSION: Gray and white MTA in conjunction with FS induce
      comparable clinical and radiographic success rate. The use of one package of MTA
      for multiple pulpotomies, combined with FS, is a cost-effective treatment.

PMID- 23534319
TI  - Comparative evaluation of formocresol and mineral trioxide aggregate in
      pulpotomized primary molars--2 year follow up.
AB  - AIM: The aim of the present study was to clinically and radiographically evaluate
      Mineral Trioxide Aggregate (MTA) as an agent for pulpotomy in primary teeth and
      to compare it with that of Formocresol (FC) pulpotomy. METHOD: Seventy first and
      second primary mandibular molars of children were chosen on patients who required
      minimum two pulpotomies in either arch or same arch. After the standardized
      technique of Pulpotomy with MTA and Formocresol, all molars were treated with a
      thick mix of Zinc oxide Eugenol cement into the coronal pulp chamber followed by
      preformed stainless steel crown. The children were followed up for clinical and
      radio graphical examination after 6, 12 and 24 month for Pain, Swelling,
      Sinus/fistula, Periapical changes, Furcation radiolucency and internal
      resorption. RESULTS: MTA represents 97% clinical success rate in comparison to
      Formocresol with 85% success. Radiographically also MTA showed more promising
      results with 88.6% success in comparison to Formocresol with 54.3%. CONCLUSIONS:
      Thus, MTA pulpotomy has emerged as an easier line of treatment to save the
      premature loss of primary teeth due to caries or trauma.

PMID- 23534320
TI  - Ribbond for treatment of complicated crown fractures: report of 3 cases.
AB  - Dental trauma is relatively common and can occur secondary to sporting injuries,
      falls, fights, or accidents. According to the International Association of Dental
      Traumatology, 50% of children experience dental trauma between the ages of 8 to
      12. There are many options for endodontic and restorative treatments of
      traumatized teeth. Ribbond, which was introduced in the market in 1992, consists
      of bondable, reinforced ultra-high strength polyethylene fibers. Ribbond may be
      an option for the treatment of traumatized teeth because of its aesthetic
      properties; absence of additional tooth preparation; and its high resistance to
      traction, which allows it to easily adapt to tooth morphology. In this report, we
      describe endodontic and restorative treatments using Ribbond for 3 female
      patients with horizontal complicated crown fractures of the maxillary incisors.

PMID- 23534321
TI  - Esthetic recovery of smile using composite resin and "biological posts" and
      crowns.
AB  - The recovery of teeth that have been extensively destroyed by dental caries can
      be achieved through direct and indirect restorative procedures. This paper
      presents a case of the esthetic and functional recovery of permanent maxillary
      incisors with extensive dental caries in an adolescent patient through the use of
      a composite resin and "biological posts and crowns". A case report was drafted to
      describe the direct restoration of central maxillary incisors using composite
      resin and endodontic treatment of the lateral maxillary incisors, the
      construction of dentinal posts, the adaptation and cementing of the posts to the
      root canals, preparation and molding of crown portions, model construction, the
      choice of extracted teeth and the making and cementing of "biological crowns".
      The use of a composite resin and the cementing of "biological posts and crowns"
      reestablish dental esthetics and function. Biological restorations maintain all
      the characteristics of natural teeth and have a significant psychosocial impact
      on the patient's quality of life. However it should be stressed that this
      technique was only indicated in the present case after the determination of a
      significant improvement in oral hygiene.

PMID- 23534322
TI  - Parental cooperation scale in the pediatric dentistry setting: reliability and
      criteria.
AB  - OBJECTIVE: The purpose of this study was to provide reliability and criteria data
      on a newly defined parental cooperation scale (PCS) and in addition correlate
      between parent scores and their child's behavior in the dental setting. STUDY
      DESIGN: 244 parents accompanying their child to a dental visit were evaluated by
      two independent pediatric dentist evaluators. 150 parents were designated to be
      revaluated at least two weeks following the initial evaluation by the same
      examiner. Children's dental behavior was previously evaluated using the Frankl
      rating scale. RESULTS: A majority of the parents were found to be highly positive
      and positive (40% of the parents were evaluated as being PCS rating 4, 26% were
      rated 3). 35% of the parents were rated as being negative or extremely negative
      (27%, 8% respectively). 139 parents were re-evaluated at least two weeks
      following their initial assessment. 64% were rated as highly cooperative and
      cooperative; 36% were negative or extremely negative. 244 children participated
      in the study (mean age +/- SD, 6.8 years +/- 2.86). 67% were rated as Frankl
      scale extremely cooperative and cooperative (31%, 35.5% respectively). 33% were
      negative or extremely negative (26.1%, 7.3% respectively). When comparing the
      Frankl behavior of each child to their parent's PCS a significant association was
      found (McNemar test value 17.668, p = 0.007). CONCLUSION: The PCS was evaluated
      and found to be a reliable tool to evaluate parental dental behavior. Parents
      with negative behavior were more likely to present with children who also exhibit
      negative dental behavior and vice versa.

PMID- 23534323
TI  - Impact of maternal xylitol consumption on mutans streptococci, plaque and caries
      levels in children.
AB  - AIM: The present study was designed to determine whether maternal xylitol
      consumption through regular chewing of xylitol gums can affect the salivary
      mutans streptococci (MS), dental caries, and dental plaque levels of their
      children. METHOD: Study sample included 60 mother and child pairs with high
      salivary mutans streptococcus (MS) levels. Samples were randomly divided into
      experimental group (30 pairs) and control group (30 pairs). Mothers in the
      experimental group received xylitol chewing gum treatment three times/day for
      three months, whereas the controls received fluoride varnish. Both groups
      received oral hygiene instructions, dietary counseling and restorative treatment.
      All children were examined after 6, 12 and 18 months from the initiation of the
      study to assess caries, plaque and salivary mutans streptococcus (MS) levels.
      RESULTS: Showed that at 18 month the percent of children with high streptococcus
      levels in the control significantly increased when compared to the increase in
      the experimental group. Throughout the study, dmft scores of experimental
      children showed marginal non significant increase compared to controls that
      showed higher scores. Plaque scores revealed statistically non significant
      decrease among both groups. CONCLUSIONS: Maternal xylitol consumption provided
      better preventive outcomes on salivary (MS) levels compared to fluoride varnish
      treatments.

PMID- 23534324
TI  - Salivary Candida, caries and Candida in toothbrushes.
AB  - BACKGROUND: Candida species are common inhabitants of the normal oral microbiota.
      A few studies founded a relationship between high levels of Candida albicans in
      the oral cavity and high DMF scores. Toothbrushes can also be reservoirs of
      microorganisms, the proliferation of these microorganism on a toothbrush could be
      a major factor for its distribution in the oral cavity. AIM: To examine the
      associations between salivary Candida and DMF, and between salivary Candida and
      Candida in the toothbrush. METHOD: 46 healthy school children, who attended a
      University pediatric dental clinic, were tested for Candida in their saliva and
      in their toothbrush. Their DMF was recorded. RESULTS: 38 children were Candida
      positive (79.2%), out of whom 5 demonstrated a positive growth of Candida in the
      toothbrushes. No correlation was found between Candida in the saliva and in the
      toothbrush. The number of Candida-positive girls was significantly higher than
      the number in boys. No significant relationship between caries experience and the
      presence of Candida was found CONCLUSIONS: No correlation was found between
      Candida in the saliva and in the toothbrush. The origin of the Candida in the
      toothbrush is not totally clear.

PMID- 23534325
TI  - Clinical measurement of maximal mouth opening in children: a pioneer method.
AB  - OBJECTIVES: To determine the maximal mouth opening (MMO) in children aged 3 to 5
      years from Indian population and to examine the possible influence of age,
      gender, height and body weight on MMO. STUDY DESIGN: Assessment of MMO is
      accomplished with a modified Vernier Caliper by measuring the distance between
      the incisal edge of upper and lower incisor during maximal mouth opening up to
      the painless limit. Participants of the study were healthy children selected
      among regular students from local schools. Age, gender height and body weight of
      each child were also recorded at the same time. RESULTS: The results of the
      present study revealed that MMO in Indian children were 41.61 mm, 44.9 mm and
      46.81 mm for boys and 40.09 mm, 44.22 mm and 46.2 mm for girls at age of 3, 4 and
      5 years respectively. Further significant associations were noted in between age,
      height, body weight and MMO. However no gender difference was observed.
      CONCLUSION: A definite relationships exist between MMO, age, height and body
      weight in Indian children with primary dentition.

PMID- 23534326
TI  - Enamel thickness in primary teeth.
AB  - OBJECTIVE: The aim of this study was to determine the enamel thickness of all
      primary teeth in both maxilla and mandible. STUDY DESIGN: An in vitro study was
      performed with fifty primary teeth including five each of central and lateral
      incisor, canine, first and second primary molars in both maxillary and mandibular
      region. Samples were mounted on wax sheets and scanned using a 64-slice CT
      scanner which were then 3D reconstructed. Three serial slices were obtained from
      the middle of the coronal portion of each tooth. Volume rendering was done to
      differentiate three distinct zones of enamel, dentin and the pulp from each
      slice. A box was constructed touching the borders of the image on all the
      surfaces and the mid-point of each side was taken to measure the enamel
      thickness. RESULTS: Tests used were ANOVA, Post-hoc Tukey's test and student's
      paired t-test. Enamel thickness was not the same on all the sides. Intergroup
      comparisons between maxillary anterior and posterior teeth showed difference in
      enamel thickness. On comparing the mandibular anterior and posterior teeth, the
      posteriors showed a greater value of enamel thickness on all the sides (p <
      0.05). CONCLUSION: Primary enamel does not follow the same thickness patterns on
      all sides. It is also different in each primary tooth. There was an increase in
      enamel thickness in posterior teeth on comparison to their anterior counterparts
      in both maxilla and mandible. Enamel thickness was more on the distal aspect
      compared to mesial in all samples.

PMID- 23534327
TI  - Adhesiveness of various glass ionomer cements in cavities treated with Carisolv.
AB  - OBJECTIVE: The purpose of this study was to investigate the adhesion of glass
      ionomer cements to dentin and the effect of pretreatment using Carisolv. STUDY
      DESIGN: Forty extracted permanent teeth with caries were used for this study. All
      lesions were removed using the Carisolv system and teeth were divided into eight
      groups. Groups 1 to 4 were filled with three types of conventional glass ionomer
      cements and a resin modified glass ionomer cement. Group 8 was restored with
      composite resin. In the remaining three groups (Groups 5 to 7), several
      pretreatment procedures, including EDTA and dentin primer application and a
      combination of these, were performed before restoring with resin modified glass
      ionomer cement. All restorations were thermocycled, and microleakage tests were
      performed on all teeth. RESULTS: There were no statistical differences among
      Groups 1, 2 and 3 or between Groups 4 and 8. However Groups 1 to 3 had higher
      microleakage levels than Groups 4 and 8. Groups 5 to 7 showed similar leakage
      levels as Group 4. CONCLUSION: Pretreatment with EDTA or dentin primer did not
      improve bonding ability. Combination of caries removal using Carisolv and a resin
      modified glass ionomer cement restoration without pretreatment seems to be an
      acceptable method for caries treatment.

PMID- 23534328
TI  - In vivo evaluation of lesion sterilization and tissue repair in primary teeth
      pulp therapy using two antibiotic drug combinations.
AB  - AIM: The purpose of this study is to evaluate and compare the clinical and
      radiographic effectiveness of Ciprofloxacin, Minocycline, Metronidazole
      combination with Ciprofloxacin, Minocycline and Tinidazole combination when used
      for Lesion Sterilization and Tissue Repair in primary teeth. METHOD: 25 healthy
      children, visiting Dept. of Pediatric & Preventive Dentistry, D.A.P.M.R.V. Dental
      College, Bangalore, India, aged between 6-9 years who were having 30 infected
      primary teeth are selected and divided into 2 groups. In Group A, a mixture of
      3mix-MP Ciprofloxacin, Metronidazole and Minocycline was placed on the floor of
      the pulp chamber covering the root canal orifices. In Group B a mixture of
      Ciprofloxacin, Tinidazole and Minocycline was placed as a layer on the floor of
      the pulp chamber. The procedure was completed in a single visit. Post operative
      clinical evaluation was done after 1,6,12 and 24 months. Postoperative
      radiographic evaluation was done at 6, 12 and 24 months. RESULTS: No
      statistically significant difference is observed between both the groups and a
      combination of Ciprofloxacin, Minocycline and Tinidazole antibacterial drugs can
      be used on teeth pulpally involved with physiologic root resorption. CONCLUSION:
      After a 24 Month follow up, we can conclude that primary teeth with the
      periradicular lesions, can be conserved by using combination of Ciprofloxacin,
      Minocycline and Tinidazole antibacterial drugs.

PMID- 23534329
TI  - Multiple supernumeraries in a non-syndromic patient.
AB  - Presence of supernumerary teeth (ST) in non-syndromic patients is an exceptional
      event. The aim of this article is to present an unusual case of a non-syndromic
      12 years old girl with 12 ST In the reported case supernumeraries were found in
      three quadrants and the most common ST were bicuspids. All ST were surgically
      excised and occlusion and functionality was restored with prosthetic appliances.
      ST are an exceedingly uncommon event in the Pediatric Clinic. An extensive review
      of the literature dealing on non-syndromic cases comprising 10 or more ST and a
      discussion about the origin of the ST is presented.

PMID- 23534330
TI  - Extreme tooth abnormalities and treatment under general anesthesia in a child
      with chronic GVHD surviving relapse of acute lymphoblastic leukemia.
AB  - Treatment for acute lymphoblastic leukemia (ALL) mainly consists of chemotherapy,
      irradiation and bone marrow transplantation. In terms of long-term treatment
      effects, dental abnormalities and chronic graft-versus host disease (GVHD) are
      problems. We present a patient surviving relapse of ALL at one year of age. He
      had extreme dental abnormalities and multiple caries. Most of his permanent teeth
      were abnormal, and multiple caries were observed. Since he had a strong vomiting
      reaction to dental treatment, general anesthesia was given. During the general
      anesthesia, much sputum was aspirated because of chronic GVHD. His dental
      condition was worse than other cases reported previously. Since the survival rate
      has increased recently, the dental effects of ALL treatment have become
      significant. Especially, in patients undergoing total body irradiation at under 2
      years of age, it is highly likely that dental problems will occur in the future.

PMID- 23534331
TI  - Orocraniofacial findings and dental management of a pediatric patient with
      Dubowitz syndrome.
AB  - Dubowitz syndrome is a rare genetic condition characterized by microcephaly,
      dysmorphic facial features and delayed general growth. It is transmitted through
      autosomal recessive inheritance. The purpose of this report is to describe the
      oral, craniofacial and systemic characteristics of a 7-year 11-month-old boy with
      Dubowitz syndrome and the dental management provided. The pediatric dentist
      should possess the ability to recognize this rare alteration, to provide dental
      treatment and to refer for the necessary medical and multidisciplinary treatment.

PMID- 23534332
TI  - Timing of permanent teeth eruption in Turkish children.
AB  - OBJECTIVE: To identify the mean time of permanent teeth eruption in children aged
      5-15 years in Samsun, Turkey. STUDY DESIGN: A total of 1,491 children aged 5-15
      years (Female: 773; Male: 718) were included in this study. Teeth were recorded
      as either "not erupted" or "erupted," which was defined as having at least one
      cusp visible in the oral cavity. Differences between eruption times for males and
      females and for maxillary and mandibular teeth were analysed using independent t
      tests. RESULTS: Eruption tended to be earlier in females than in males, but this
      difference was significant only for maxillary and mandibular canines and
      mandibular first premolars (p < 0.05). For both females and males, the first
      teeth to erupt were the central incisors and first molars, and the last to erupt
      were the second premolars, molars and canines. Mandibular incisors and canines
      erupted significantly earlier than their maxillary counterparts in both females
      and males (p < 0.05). CONCLUSION: In comparison with other studies, eruption
      times ofpermanent first molars, central and lateral incisors were delayed by
      several months, whereas eruption times of other teeth were accelerated by several
      months. The findings regarding eruption times should be considered when planning
      dental treatment.

PMID- 23534333
TI  - A computerized photographic method to evaluate changes in head posture and
      scapular position following rapid palatal expansion: a pilot study.
AB  - OBJECTIVE: To assess the applicability of a computerized method to measure on
      digital photographs the changes in head and scapular posture following rapid
      palatal expansion (RPE) treatment. STUDY DESIGN: Randomized controlled trial.
      Twenty-three children (age 9.2 +/- 70.88 years) diagnosed with maxillary
      constriction were randomly divided into two groups: 1. Study group (n = 12):
      patients receiving RPE treatment; 2. Untreated controls (n = 11). Postural
      measurements were taken on frontal, lateral, and dorsal views of each subject. In
      the study group measurements were taken at T0 (the day orthodontic records were
      taken), T1 (end of RPE active phase), and T2 (RPE removal). In controls the same
      observations were conducted at T0 and T1(98.18 +/- 36.01 days after T0).
      Measurements were statistically analyzed (Intraclass Correlation Coefficient, t
      tests, Signed Rank test, One-Way Repeated Measures Analysis of Variance, Tukey
      test; p < 0.05). RESULTS: In the study group a significant reduction in forward
      head posture (FHP) occurred between T0 and T1. Forward shoulder posture (FSP)
      decreased significantly between T1 and T2. At T1 treated patients exhibited
      significantly lower values of the measurements indicating FHP and FSP than
      controls. CONCLUSION: Changes in head and scapular posture following RPE
      treatment can be documented with computerized measurements on digital
      photographs.

PMID- 23534334
TI  - Maxillary protraction at early ages. The revolution of new bone anchorage
      appliances.
AB  - PURPOSE: An update is provided on the different types of early treatment for
      class III malocclusions of maxillary origin. There is an increasing tendency to
      prescribe maxillary orthopedic treatment with skeletal anchorage, with the
      purpose of enhancing the skeletal and reducing the dentoalveolar effects-
      offering a management option for children with important deformations that
      otherwise would have to wait until adult age to receive surgical treatment.
      METHOD: A literature review has been made of maxillary bone orthopedic traction
      appliances in growing children with class III malocclusions. A Medline (PubMed)
      search was made using the following MeSH terms: Cephalometric, Child,
      Malocclusion class III/therapy, Extraoral traction appliances, Palatal expansion,
      Bone plates, Skeletal anchorage, Orthodontic anchorage. RESULTS: Many articles
      show that the greatest maxillary advances are obtained at very early ages, though
      with a greater tendency towards relapse. However skeletal anchorage has been seen
      to afford a lesser relapse rate and greater dentofacial orthopedic efficiency due
      to its low dentoalveolar impact. In any case, further randomized clinical studies
      are needed to firmly establish the quantifiable differences in terms of maxillary
      advance, optimum traction age, optimum traction appliance and potential side
      effects. At present, the incorporation of surgically inserted bone anchorage
      appliances (miniplates and miniscrews) offers a purely orthopedic approach to
      treatment, with minimization of the undesirable side effects of traditional
      dentofacial orthopedic compensation based on dentoalveolar anchorage.
      Nevertheless, further studies are needed to consolidate the supporting scientific
      evidence in this field.

PMID- 23534335
TI  - Stereospecific Suzuki, Sonogashira, and Negishi coupling reactions of N
      alkoxyimidoyl iodides and bromides.
AB  - A high-yielding stereospecific route to the synthesis of single geometric isomers
      of diaryl oxime ethers through Suzuki coupling of N-alkoxyimidoyl iodides is
      described. This reaction occurs with complete retention of the imidoyl halide
      geometry to give single E- or Z-isomers of diaryl oxime ethers. The Sonogashira
      coupling of N-alkoxyimidoyl iodides and bromides with a wide variety of terminal
      alkynes to afford single geometric isomers of aryl alkynyl oxime ethers has also
      been developed. Several of these reactions proceed through copper-free
      conditions. The Negishi coupling of N-alkoxyimidoyl halides is introduced. The E
      and Z configurations of nine Suzuki-coupling products and two Sonogashira
      coupling products were confirmed by X-ray crystallography.

PMID- 23534336
TI  - Mechanical and viscoelastic properties of cellulose nanocrystals reinforced
      poly(ethylene glycol) nanocomposite hydrogels.
AB  - The preparation and mechanical properties of elastomeric nanocomposite hydrogels
      consisting of cellulose nanocrystals (CNCs) and poly(ethylene glycol) (PEG) are
      reported. The aqueous nanocomposite CNC/PEG precursor solutions covalently cross
      linked through a one-stage photocross-linking process. The mechanical properties
      of nanocomposite hydrogels, including Young's modulus (E), fracture stress
      (sigma), and fracture strain (epsilon), were measured as a function of CNC volume
      fraction (phiCNC, 0.2-1.8%, v/v) within polymeric matrix. It was found that the
      homogeneously dispersed nanocomposite hydrogels can be prepared with phiCNC being
      less than 1.5%, whereas the heterogeneous nanocomposite hydrogels were obtained
      with phiCNC being higher than 1.5%. The nanocomposite hydrogels exhibited higher
      strengths and flexibilities when compared with neat PEG hydrogels, where the
      modulus, fracture stress, and fracture strain enhanced by a factor of 3.48, 5,
      and 3.28, respectively, over the matrix material alone at 1.2% v/v CNC loading.
      Oscillatory shear data indicated the CNC-PEG nanocomposite hydrogels were more
      viscous than the neat PEG hydrogels and were efficient at energy dissipation due
      to the reversible interactions between CNC and PEG polymer chains. It was
      proposed that the strong gel viscoelastic behavior and the mechanical
      reinforcement were related to "filler network", where the temporary interactions
      between CNC and PEG interfered with the covalent cross-links of PEG.

PMID- 23534337
TI  - Harm, hype and evidence: ELSI research and policy guidance.
AB  - There has been much investment in research on the ethical, legal and social
      issues (ELSI) associated with genetic and genomic research. This research should
      inform the development of the relevant policy. So far, much of the relevant
      policy - such as in the areas of patents, genetic testing and genetic
      discrimination - seems to be informed more by speculation of harm and anecdote
      than by available evidence. Although a quest for evidence cannot always be
      allowed to delay policy choice, it seems axiomatic to us that policy options are
      improved by the incorporation of evidence. 

PMID- 23534338
TI  - Exit channel dynamics in a micro-hydrated SN2 reaction of the hydroxyl anion.
AB  - We report on the reaction dynamics of the monosolvated SN2 reaction of cold OH(
      )(H2O) with CH3I that have been studied using crossed beam ion imaging. Two SN2
      reaction channels are possible for this reaction: Formation of unsolvated I(-)
      and of solvated I(-)(H2O) products. We find a strong preference for the formation
      of unsolvated I(-) reaction products with respect to the energetically favored
      reaction toward solvated I(-)(H2O). Angle differential cross section measurements
      reveal similar velocity and angular distributions for all solvated and parts of
      the unsolvated reaction products. We furthermore find that the contribution of
      these two products to the total product flux can be described by the same
      collision energy dependence. We interpret our findings in terms of a joint
      reaction mechanism in which a CH3OH(H2O)...I(-) complex is formed that decays
      into either solvated or unsolvated products. Quantum chemical calculation are
      used to support this assumption. 

PMID- 23534339
TI  - Analytical expressions for proton transfer voltammetry: analogy to surface redox
      voltammetry with Frumkin interactions.
AB  - Theory for interfacial proton transfer voltammetry of a molecular film containing
      any acid/base loading has been developed under equilibrium conditions. Diagnostic
      criteria to disentangle the interplay between diffuse layer and ionization
      effects are outlined. Easy-to-use analytical expressions for the voltammetric
      features are derived for the particular case of an invariant diffuse layer
      effect, which turn out to be entirely analogous to those for a surface redox
      conversion with Frumkin interactions. It is demonstrated that, regardless of the
      electrolyte concentration, significant ionization of the external acid groups
      located nearby the diffuse layer is sufficient for the fulfillment of this
      relevant particular case. A strategy is outlined to determine the amount, the
      intrinsic pKa, and the burial depth of the voltammetrically active groups from
      the surface concentration dependence of the main voltammetric features. Self
      assembled monolayers of 11-mercaptoundecanoic acid deposited on Au(111),
      containing higher amounts of buried carboxylic groups than previously reported,
      have been studied to assess more critically the influence of electrostatic
      effects on the ionization process. Preliminary evidence suggests that the
      protonation/deprotonation voltammetric wave involves physisorbed rather than
      chemisorbed thiol molecules. Application of the present theoretical approach to
      this system reveals that the voltammetrically active carboxylic groups are
      located close to the electrode surface and become more acidic upon increasing
      their surface concentration. 

PMID- 23534341
TI  - Deep impact of the template on molecular weight, structure, and oxidation state
      of the formed polyaniline.
AB  - In this work we find that polyaniline (PANI), synthesized by aniline chemical
      polymerization at a surface of template polycarbonate (PC) particles, is
      significantly different in molecular weight, structural order, oxidation state,
      and conductivity from a neat PANI. Molecular weight of the PANI phase in the
      composite (Mw = 158,000) is 1.6 times higher than that of the neat PANI
      synthesized in the absence of the template particles. Moreover, XRD analysis
      shows that crystallinity of the PANI phase in the composite is three times higher
      than that of the neat PANI. Raman spectroscopy indicates that the oxidation level
      of PANI in the PC/PANI composite is lower than that of the neat PANI. These
      noticeable changes of the PANI phase properties suggest specific interactions of
      reagents in the polymerization medium and formed PANI with the template phase as
      well as an orientation effect of the latter surface. FTIR spectroscopy reveals
      that hydrogen bonding in the neat doped PANI is weaker than one between -NH- of
      PANI and C?O of PC at their interface. The discovered differences are supported
      by the fact that conductivity of the PANI phase in the composite is more than
      three times higher than that of the neat PANI.

PMID- 23534340
TI  - Anesthetic considerations in patients with mitochondrial defects.
AB  - Mitochondrial disease, once thought to be a rare clinical entity, is now
      recognized as an important cause of a wide range of neurologic, cardiac, muscle,
      and endocrine disorders . The incidence of disorders of the respiratory chain
      alone is estimated to be about 1 per 4-5000 live births, similar to that of more
      well-known neurologic diseases . High-energy requiring tissues are uniquely
      dependent on the energy delivered by mitochondria and therefore have the lowest
      threshold for displaying symptoms of mitochondrial disease. Thus, mitochondrial
      dysfunction most commonly affects function of the central nervous system, the
      heart and the muscular system . Mutations in mitochondrial proteins cause
      striking clinical features in those tissues types, including encephalopathies,
      seizures, cerebellar ataxias, cardiomyopathies, myopathies, as well as
      gastrointestinal and hepatic disease. Our knowledge of the contribution of
      mitochondria in causing disease or influencing aging is expanding rapidly . As
      diagnosis and treatment improve for children with mitochondrial diseases, it has
      become increasingly common for them to undergo surgeries for their long-term
      care. In addition, often a muscle biopsy or other tests needing anesthesia are
      required for diagnosis. Mitochondrial disease represents probably hundreds of
      different defects, both genetic and environmental in origin, and is thus
      difficult to characterize. The specter of possible delayed complications in
      patients caused by inhibition of metabolism by anesthetics, by remaining in a
      biochemically stressed state such as fasting/catabolism, or by prolonged exposure
      to pain is a constant worry to physicians caring for these patients. Here, we
      review the considerations when caring for a patient with mitochondrial disease. 

PMID- 23534342
TI  - In vitro approaches to evaluate toxicity induced by organotin compounds
      tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) in neuroblastoma
      cells.
AB  - The toxic effects of the organotin compounds (OTCs) monobutyltin (MBT),
      dibutyltin (DBT), and tributyltin (TBT) were evaluated in vitro in a
      neuroblastoma human cell line. Mechanisms of cell death, apoptosis versus
      necrosis, were studied by using several markers: inhibition of cell viability and
      proliferation, F-actin, and mitochondrial membrane potential changes as well as
      reactive oxygen species (ROS) production and DNA fragmentation. The most toxic
      effects were detected with DBT and TBT even at very low concentrations (0.1-1
      MUM). In contrast, MBT induced lighter cytotoxic changes at the higher doses
      tested. None of the studied compounds stimulated propidium iodide uptake,
      although the most toxic chemical, TBT, caused lactate dehydrogenase release at
      the higher concentrations tested. These findings suggest that in neuroblastoma,
      OTC-induced cytotoxicity involves different pathways depending on the compound,
      concentration, and incubation time. A screening method for DBT and TBT
      quantification based on cell viability loss was developed, allowing a fast
      detection alternative to complex methodology. 

PMID- 23534343
TI  - A comparison of teeth and implants during maintenance therapy in terms of the
      number of disease-free years and costs -- an in vivo internal control study.
AB  - BACKGROUND: Little is known about the cost minimization and cost effectiveness
      involved in maintaining teeth and implants for patients treated for periodontal
      disease. MATERIALS & METHODS: A retrospective study was carried out encompassing
      all patients who had initial periodontal treatment followed by implant placement
      and maintenance therapy in a specialist practice in Norway. The neighbouring
      tooth and the contra-lateral tooth were used as controls. The number of disease
      free years and the extra cost over and above maintenance treatment for both teeth
      and implants were recorded. RESULTS: The sample consisted of 43 patients with an
      average age of 67.4 years. The patients had 847 teeth at the initial examination
      and received 119 implants. Two implants were removed 13 and 22 years after
      insertion. The prevalence of peri-implantitis was 53.5% at the patient level and
      31.1% at the implant level. The prevalence of periodontitis was 53.4% at the
      patient level and 7.6% at the tooth level. The mean number of disease-free years
      was: implants: 8.66; neighbouring tooth: 9.08; contra-lateral teeth: 9.93. These
      mean values were not statistically significantly different from each other. The
      extra cost of maintaining the implants was about five times higher for implants
      than for teeth. CONCLUSION: The number of disease-free years was the same for
      neighbouring teeth, contra-lateral teeth and implants. However, due to the high
      prevalence of peri-implantitis, the cost of maintaining implants was much higher
      than the cost of maintaining teeth.

PMID- 23534344
TI  - Ectopic expression of wheat TaCIPK14, encoding a calcineurin B-like protein
      interacting protein kinase, confers salinity and cold tolerance in tobacco.
AB  - Calcineurin B-like protein-interacting protein kinases (CIPKs) are components of
      Ca(2+) signaling in responses to abiotic stresses. In this work, the full-length
      cDNA of a novel CIPK gene (TaCIPK14) was isolated from wheat and was found to
      have significant sequence similarity to OsCIPK14/15. Subcellular localization
      assay revealed the presence of TaCIPK14 throughout the cell. qRT-PCR analysis
      showed that TaCIPK14 was upregulated under cold conditions or when treated with
      salt, PEG or exogenous stresses related signaling molecules including ABA,
      ethylene and H2 O2 . Transgenic tobaccos overexpressing TaCIPK14 exhibited higher
      contents of chlorophyll and sugar, higher catalase activity, while decreased
      amounts of H2 O2 and malondialdehyde, and lesser ion leakage under cold and salt
      stresses. In addition, overexpression also increased seed germination rate, root
      elongation and decreased Na(+) content in the transgenic lines under salt stress.
      Higher expression of stress-related genes was observed in lines overexpressing
      TaCIPK14 compared to controls under stress conditions. In summary, these results
      suggested that TaCIPK14 is an abiotic stress-responsive gene in plants.

PMID- 23534345
TI  - Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on
      hydrogen peroxide-induced oxidative stress in rat cortical cell culture.
AB  - Resveratrol (RES) has recently been reported as a potential antioxidant in
      treatment of ischemia/reperfusion injury through attenuating oxidative stress and
      apoptosis. However, application of RES is limited for its insolubility and short
      half-time. Latest evidence raises the possibility of developing nanoparticle
      based delivery systems with improved solubility, stability and cytotoxicity of
      lipophilic drug. Here, we reported first a simple way to produce RES-loaded
      nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b-poly(epsilon
      caprolactone) polymer and further evaluated the protective effect of RES-NPs on
      hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell
      culture. The controlled release pattern of RES-loaded nanoparticles was
      characterized by in vitro release experiments. Cytotoxicity tests proved
      cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded
      nanoparticles, the uptake of nanoparticles by neurons was considered through
      endocytosis, which could lead to higher uptake efficiency at lower concentration.
      Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced
      neuroprotection compared to an equivalent dose of free RES at lower
      concentration, especially. It was further supported by enhanced reduction of LDH
      release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio
      of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment
      needing intensive research for ischemia/reperfusion related disorder including
      stroke.

PMID- 23534346
TI  - Platinum-mediated dinitrogen liberation from 2-picolyl azide through a putative
      Pt?N double bond containing intermediate.
AB  - 2-Picolyl azide reacts with cis-[PtCl2(DMSO)2] to form the diimino complex
      [Pt(II)Cl2{NH?C(H)Py}] with subsequent dinitrogen liberation. The formation of
      the latter complex is scrutinized in a combined experimental and theoretical
      analysis. We establish in silico that the transformation involves a highly
      reactive intermediate containing a Pt?N double bond formed after the extrusion of
      N2 from the azide functionality. The prerequisites for N2 liberation and for the
      stabilization of the nitrene-related intermediate are analyzed in detail.

PMID- 23534347
TI  - Evaluation of the Cardiac Depression Visual Analogue Scale in a medical and non
      medical sample.
AB  - Comorbid depression and medical illness is associated with a number of adverse
      health outcomes such as lower medication adherence and higher rates of subsequent
      mortality. Reliable and valid psychological measures capable of detecting a range
      of depressive symptoms found in medical settings are needed. The Cardiac
      Depression Visual Analogue Scale (CDVAS) is a recently developed, brief six-item
      measure originally designed to assess the range and severity of depressive
      symptoms within a cardiac population. The current study aimed to further
      investigate the psychometric properties of the CDVAS in a general and medical
      sample. The sample consisted of 117 participants, whose mean age was 40.0 years
      (SD = 19.0, range 18-84). Participants completed the CDVAS, the Cardiac
      Depression Scale (CDS), the Depression Anxiety Stress Scales (DASS) and a
      demographic and health questionnaire. The CDVAS was found to have adequate
      internal reliability (alpha = .76), strong concurrent validity with the CDS (r =
      .89) and the depression sub-scale of the DASS (r = .70), strong discriminant
      validity and strong predictive validity. The principal components analysis
      revealed that the CDVAS measured only one component, providing further support
      for the construct validity of the scale. Results of the current study indicate
      that the CDVAS is a short, simple, valid and reliable measure of depressive
      symptoms suitable for use in a general and medical sample.

PMID- 23534348
TI  - Risk factors for recurrence after curative resection of hepatitis C-related
      hepatocellular carcinoma in patients without postoperative interferon therapy.
AB  - AIM: Hepatitis C (HC)-related hepatocellular carcinoma (HCC; HC-HCC) is highly
      recurrent. METHODS: From 1995-2007, 183 curative hepatic resections for primary
      solitary HC-HCC without postoperative interferon therapy were included in this
      study. The patients were divided into three groups: (i) 2 cm or less (n = 56);
      (ii) more than 2 cm to less than 5 cm (n = 79); and (iii) 5 cm or more (n = 48).
      Independent risk factors for HC-HCC recurrence for each group were determined.
      RESULTS: Independent risk factors for recurrence were aspartate aminotransferase
      or alanine aminotransferase (AST/ALT) of 80 IU/L or more (hazard ratio [HR], 2.1;
      P = 0.02) in patients with HCC of 2 cm or less, des-gamma-carboxy prothrombin of
      100 mAU/mL or more (HR, 2.5; P = 0.02) and AST/ALT of 80 IU/L or more (HR, 2.1; P
      = 0.04) in patients with HCC of more than 2 cm to less than 5 cm, and the
      presence of macroscopic portal vein tumor thrombus (HR, 2.8; P = 0.02) and
      AST/ALT of 80 IU/L or more (HR, 2.1; P = 0.04) in patients with HCC of 5 cm or
      more. All 13 late recurrences of 1 year or more after hepatic resection (27.1%)
      in patients with HCC of 5 cm or more were accompanied by AST/ALT of 80 IU/L or
      more. CONCLUSION: AST/ALT of 80 IU/L or more is an independent risk factor for
      the recurrence of primary solitary HC-HCC after curative resection irrespective
      of the primary HC-HCC size.

PMID- 23534350
TI  - Is there a relationship between disease duration and P-wave dispersion in
      patients with psoriasis?

PMID- 23534349
TI  - Generalization of variants identified by genome-wide association studies for
      electrocardiographic traits in African Americans.
AB  - Electrocardiographic (ECG) measurements vary by ancestry. Genome-wide association
      studies (GWAS) have identified loci that contribute to ECG measurements; however,
      most are performed in Europeans collected from population-based cohorts or
      surveys. The strongest associations reported are in NOS1AP with QT interval and
      SCN10A with PR and QRS durations. The extent to which these associations can be
      generalized to African Americans has yet to be determined. Using electronic
      medical records, PR and QT intervals, QRS duration, and heart rate were
      determined in 455 African Americans as part of the Vanderbilt Genome-Electronic
      Records Project and Northwestern University NUgene Project. We tested for an
      association between these ECG traits and >930K SNPs. We identified a total 36
      novel associations with PR interval, QRS duration, QT interval, and heart rate at
      p < 1.0 * 10(-6). Using published GWAS data, we compared our results with those
      previously identified in other populations. Five associations originally
      identified in other populations generalized with respect to statistical
      significance and direction of effect. A total of 43 associations have a
      consistent direction of effect with European and/or Asian populations. This work
      provides a catalogue of generalized versus nongeneralized associations, a
      necessary step in prioritizing GWAS-identified regions for further fine-mapping
      in diverse populations. 

PMID- 23534351
TI  - A novel experimental model for studying transverse orthodontic tooth movement in
      the rat mandible.
AB  - OBJECTIVES: To establish a rat model of a one-piece mandible using the principles
      of gingivoperiosteoplasty and guided bone regeneration to fuse the midline
      symphyseal area. MATERIAL AND METHODS: Twenty-four Sprague-Dawley female rats
      were divided into two groups: 12 experimental and 12 control. Both groups were
      imaged using in vivo micro-computed tomography at baseline and at end point (5
      months). The experimental group received regenerative surgery at the symphysis
      area; the control group received no treatment. Outcomes were evaluated by
      radiographic examination of gross and volumetric bony changes in the symphyseal
      region of interest marked between the mental foramina bilaterally and the two
      central incisors near the most coronal margin of the alveolar crests. These
      landmarks were chosen as they can be reproduced on the computed tomography images
      at baseline and end point. Histologic examination was performed on all samples at
      a level 5 mm apical to the alveolar bone crest. RESULTS: Radiologic and
      histologic examinations of the experimental group revealed complete bony fusion
      of the symphyseal area in three subjects, partial fusion in five subjects, and
      thickening of the alveolar bony socket in three subjects; one rat died of
      anesthesia-related complications. No evidence of fusion or alveolar bone
      thickening was found in any of the controls. CONCLUSIONS: This surgical animal
      model demonstrates that a rat mandible can be surgically manipulated to mimic the
      one-piece human mandible. This novel model may prove useful in studying
      mandibular bone remodeling and orthodontic mandibular tooth movement.

PMID- 23534352
TI  - Value of vanin-1 assessment in adult patients with primary immune
      thrombocytopenia.
AB  - The diagnosis of primary immune thrombocytopenia (ITP) is clinical and cannot be
      established by any specific laboratory assay. Perhaps the best diagnostic study
      is assessment of the patient's response to ITP therapy. Oxidative stress-related
      pathways were among the most significant chronic ITP-associated pathways.
      Overexpression of VNN1 gene, an oxidative stress sensor in epithelial cells, was
      most strongly associated with progression to chronic ITP. To address this issue,
      we tested the hypothesis that blood vanin-1 protein level could distinguish
      between chronic responders and non-responders ITP patients as well as between ITP
      patients and healthy controls. Vanin-1 protein levels were determined in
      peripheral blood leukocytes of 80 adult subjects (16 newly diagnosed ITP
      patients, 24 chronic responders ITP patients, 24 chronic non-responders ITP
      patients and 16 healthy controls) by enzyme-linked immunesorbent assay (ELISA).
      Blood vanin-1 protein levels were lower in controls (median = 18.39 ng) than in
      ITP patients (median = 58.78 ng) with a highly significant p value (p < 0.001).
      Vanin-1 levels were highly significantly elevated in newly diagnosed ITP patients
      (median = 188.62 ng) in comparison to chronic responders (median= 26.90 ng) and
      chronic non-responders (median = 73.87 ng). Vanin-1 level at a cut-off value of
      >20.73 ng was found to be 100% sensitive and 93.7% specific in discriminating
      between newly diagnosed ITP patients and healthy controls. Vanin-1 level was
      found to be 100% sensitive and 100% specific in differentiating between
      responders and non-responders with a cut-off value of <= 34.5 ng. Our results
      suggest that vanin-1 can distinguish between chronic responders and non
      responders ITP patients as well as between newly diagnosed ITP patients and
      healthy controls. These findings demonstrate that vanin-1 may contribute to the
      pathogenesis of ITP, indicating that vanin-1 is an important target for further
      investigation.

PMID- 23534353
TI  - Expression of heat shock protein 70 in the liver of extensively and intensively
      kept heavy pigs.
AB  - The objective of this work was to investigate the expression of heat shock
      protein 70 (HSP70) by Western blot (WB) in swine liver. Subsequently, the study
      aimed to apply this method to two experimental groups of heavy pigs raised in
      different confinement systems: intensive/indoor (Group A) and extensive/outdoor
      (Group B). Thirty-six crossbred commercial heavy pigs were divided as follows:
      Group A (eight castrated males and eight females) was equally distributed into
      two single-sex indoor pens (1.02 m2/pig); Group B (11 castrated males and nine
      females) was kept in one single (partially grassy and partially wooded) open area
      of about 6000 m2. Group A was slaughtered at 41 weeks of age (170 +/- 9 kg) and
      Group B at 48 weeks of age (172 +/- 13 kg). At the abattoir the livers of all the
      animals were collected and analyzed by WB assay in order to quantify the levels
      of HSP70. Moreover, a further liver sample was taken from the same animals in
      order to investigate the cellular localization of HSP70 by immunohistochemistry
      (IHC). The interaction between sex and group resulted statistically significant
      (P = 0.001). When stratified by sex, Group A showed significantly higher HSP70
      values compared with Group B for both male and female subjects (P < 0.001).
      Stratifying by group, males showed significantly higher HSP70 values than females
      in Group A (P < 0.001), whereas no statistical differences were observed between
      sexes for Group B (P = 0.653). The IHC results evidenced cytoplasmic
      immunoreactivity in a granular pattern in both groups. The different expression
      pattern observed by WB could prove to be a useful tool in the assessment of pig
      health and welfare.

PMID- 23534354
TI  - Vaginal lubrication after cervicovaginal stimulation is facilitated by
      phosphodiesterase type 5 inhibition in ovariectomized mice.
AB  - INTRODUCTION: Nitric oxide synthases (NOSs) and estrogen receptors are expressed
      in the vagina. AIM: We aimed to assess the impact of sildenafil on vaginal
      lubrication according to the hormonal status and to determine the role of the
      neuronal isoform of NOS (nNOS). METHODS: Four-week-old C57/BL6 female mice were
      sham operated or ovariectomized. At 10 weeks of age, they were injected
      intraperitoneally by any combination of sildenafil, 7-nitroindazole (7-NI)--a
      potent selective nNOS inhibitor--or the corresponding vehicles. Vaginal
      lubrication was induced in a physiological manner by cervical vaginal probing and
      quantified depending on the hormonal and pharmacological conditions. The animals
      were then sacrificed for vaginal histomorphometry. MAIN OUTCOME MEASURES: The
      main outcome measure is the quantification of vaginal transudate after
      cervicovaginal stimulation and vaginal histomorphometry. RESULTS: Sildenafil
      increased cervicovaginal probing-induced vaginal lubrication in ovariectomized
      and sham-operated animals. Ovariectomized mice exhibited decreased vaginal
      lubrication as compared with sham-operated mice. When taking into account the
      presence of severe vaginal atrophy, a threefold increase in transudate per gram
      of vagina wet weight was revealed in ovariectomized animals. Castration markedly
      reduced the thickness of the vaginal wall. nNOS inhibition by 7-NI had no impact
      on vaginal lubrication. CONCLUSIONS: Irrespective of the hormonal status,
      sildenafil increased vaginal lubrication. The vaginal effect of sildenafil was
      independent of the nNOS pathway and more pronounced in ovariectomized animals.

PMID- 23534355
TI  - Staphylococcus aureus and CCR5: unveiling commonalities in host-pathogen
      interactions and potential treatment strategies.

PMID- 23534357
TI  - Rapid antigen-based testing for respiratory syncytial virus: moving diagnostics
      from bench to bedside?
AB  - Respiratory syncytial virus (RSV) is the most important cause of infantile
      bronchiolitis and pneumonia. It is ubiquitous, with most children acquiring their
      primary infection within the first year of life and with subsequent reinfection
      occurring in all age groups. Clinically, RSV is virtually indistinguishable from
      other viral respiratory infections. Traditionally, the microbiologic diagnosis of
      RSV has been based on moderate to complex techniques performed in a laboratory
      (cell culture, nucleic acid amplification and immunofluorescence assays);
      however, rapid antigen-detection tests offer potential advantages associated with
      point-of-care testing. This review seeks to familiarize the readers with RSV
      rapid antigen-detection tests, describe their performance characteristics and
      comment on their strengths and weaknesses. The authors will discuss the impact of
      rapid RSV testing on clinical practice, with a look to the future of what the
      field ultimately requires of a point-of-care diagnostic technique.

PMID- 23534359
TI  - Hendra virus: a one health tale of flying foxes, horses and humans.
AB  - Hendra virus, a member of the family Paramyxoviridae, was first recognized
      following a devastating outbreak in Queensland, Australia, in 1994. The naturally
      acquired symptomatic infection, characterized by a rapidly progressive illness
      involving the respiratory system and/or CNS, has so far only been recognized in
      horses and humans. However, there is potential for other species to be infected,
      with significant consequences for animal and human health. Prevention of
      infection involves efforts to interrupt the bat-to-horse and horse-to-human
      transmission interfaces. Education and infection-control efforts remain the key
      to reducing risk of transmission, particularly as no effective antiviral
      treatment is currently available. The recent release of an equine Hendra G
      glycoprotein subunit vaccine is an exciting advance that offers the opportunity
      to curb the recent increase in equine transmission events occurring in endemic
      coastal regions of Australia and thereby reduce the risk of infection in humans.

PMID- 23534360
TI  - Dual-functioning antimalarials that inhibit the chloroquine-resistance
      transporter.
AB  - Malaria remains a major international health challenge. Resistance to a number of
      existing drugs and evidence of the emergence of artemisinin resistance has
      emphasized the need for new antimalarials. A new approach has been the
      preparation of dual-function compounds that include a chloroquine-like
      antimalarial group and a group that resembles a chloroquine chemosensitizer. This
      article reviews the recent discovery of such dual-function antimalarials that are
      proposed to target both hemozoin formation and the chloroquine resistance
      transporter, PfCRT. These are discussed in relation to the mechanism of action of
      4-aminoquinolines, chloroquine resistance and resistance reversal.

PMID- 23534358
TI  - Bacterial oncogenesis in the colon.
AB  - The human colon plays host to a diverse and metabolically complex community of
      microorganisms. While the colonic microbiome has been suggested to contribute to
      the development of colorectal cancer (CRC), a definitive link has not been made.
      The role in which the colon microflora could contribute to the initiation and/or
      progression of CRC is explored in this review. Potential mechanisms of bacterial
      oncogenesis are presented, along with lines of evidence derived from animal
      models of microbially induced CRC. Particular focus is given to the oncogenic
      capabilities of enterotoxigenic Bacteroides fragilis. Recent progress in defining
      the microbiome of CRC in the human population is evaluated, and the future
      challenges of linking specific etiologic agents to CRC are emphasized.

PMID- 23534361
TI  - Inhibition of drug efflux pumps in Staphylococcus aureus: current status of
      potentiating existing antibiotics.
AB  - The emergence of multidrug-resistant Staphylococcus aureus coupled with a
      declining output of new antibiotic treatment options from the pharmaceutical
      industry is a growing worldwide healthcare problem. Multidrug efflux pumps are
      known to play a role in antibiotic and biocide resistance in S. aureus. These
      membrane transporters are capable of extruding drugs and other structurally
      unrelated compounds, hence decreasing intracellular concentration and increasing
      survival. Coadministration of efflux pump inhibitors (EPIs) with antibiotics that
      are pump substrates could increase intracellular drug levels, thus bringing
      renewed efficacy to existing antistaphylococcal agents. Numerous EPIs have been
      identified or synthesized over the past two decades; these include existing
      pharmacologic drugs, naturally occurring compounds, and synthetic derivatives
      thereof. This review describes the current progress in EPI development for use
      against S. aureus.

PMID- 23534362
TI  - Biomolecular mechanisms of staphylococcal biofilm formation.
AB  - The multitude of biomolecular and regulatory factors involved in staphylococcal
      adhesion and biofilm formation owe much to their ability to colonize surfaces,
      allowing the biofilm form to become the preferential bacterial phenotype. Judging
      by total number, biomass and variety of environments colonized, bacteria can be
      categorized as the most successful lifeform on earth. This is due to the ability
      of bacteria and other microorganisms to respond phenotypically via biomolecular
      processes to the stresses of their surrounding environment. This review focuses
      on the specific pathways involved in the adhesion of the Gram-positive bacteria
      Staphylococcus epidermidis and Staphylococcus aureus with reference to the role
      of specific cell surface adhesins, the ica operon, accumulation-associated
      proteins and quorum-sensing systems and their significance in medical device
      related infection.

PMID- 23534364
TI  - Nuclear magnetic resonance applied to antimicrobial drug susceptibility.
AB  - There are many conventional microbiological methods in routine clinical practice
      to determine the sensitivity of common bacteria. The problem with these methods
      arises with bacteria that do not grow on habitual media (Rickettsia spp.,
      Coxiella spp. and Anaplasma spp., among others) and for which there are no
      standardized techniques to determine their antimicrobial susceptibility. In
      addition, the techniques that are used for the culture of these fastidious
      bacteria show problems in both accuracy and reproducibility and, in some cases,
      the in vitro antimicrobial susceptibility of bacteria shows poor correlation with
      therapeutic outcome. Therefore, it becomes difficult to determine the
      antimicrobial drug susceptibility of some bacteria and, thus, to assess the
      therapeutic effect of drugs. The scientific breakthroughs that have taken place
      in recent years have allowed the use of new techniques that facilitate and
      improve microbiological study. This paper reviews the use of nuclear magnetic
      resonance spectroscopy as an alternative tool for determining antimicrobial drug
      susceptibility.

PMID- 23534363
TI  - Polysaccharide export outer membrane proteins in Gram-negative bacteria.
AB  - Polysaccharide export outer membrane proteins of Gram-negative bacteria are
      involved in the export of polysaccharides across the outer membrane. The
      mechanisms of polysaccharide export across the outer membrane in Gram-negative
      bacteria are not yet completely clear. However, the mechanisms of polysaccharide
      assembly in Escherichia coli have been intensively investigated. Here, we mainly
      review the current understanding of the assembly mechanisms of group 1 capsular
      polysaccharide, group 2 capsular polysaccharide and lipopolysaccharide of E.
      coli, and the current structures and interactions of some polysaccharide export
      outer membrane proteins with other proteins involved in polysaccharide export in
      Gram-negative bacteria. In addition, LptD may be targeted by peptidomimetic
      antibiotics in Gram-negative bacteria. We also give insights into the directions
      of future research regarding the mechanisms of polysaccharide export.

PMID- 23534365
TI  - Immunoproteomics and immunoinformatics analysis of Cryptococcus gattii: novel
      candidate antigens for diagnosis.
AB  - AIM: To identify immunoreactive proteins of Cryptococcus gattii genotype VGII and
      their B-cell epitopes. MATERIALS & METHODS: We combined 2D gel electrophoresis,
      immunoblotting and mass spectrometry to identify immunoreactive proteins from
      four strains of C. gattii genotype VGII (CG01, CG02, CG03 and R265). Next, we
      screened the identified proteins to map B-cell epitopes. RESULTS: Sixty-eight
      immunoreactive proteins were identified. The strains and the number of proteins
      we found were: CG01 (12), CG02 (12), CG03 (18) and R265 (26). In addition, we
      mapped 374 peptides potentially targeted by B cells. CONCLUSION: Both
      immunoreactive proteins and B-cell epitopes of C. gattii genotype VGII that were
      potentially targeted by a host humoral response were identified. Considering the
      evolutionary relevance of the identified proteins, we may speculate that they
      could be used as the initial targets for recombinant protein and peptide
      synthesis aimed at the development of immunodiagnostic tools for cryptococcosis.

PMID- 23534367
TI  - Hemicrania continua responsive to botulinum toxin type a: a case report.
AB  - BACKGROUND: Hemicrania continua (HC) is a primary headache disorder with full
      response to indomethacin as one of its diagnostic criteria; however,
      indomethacin's side effects could limit its use in HC. CASE RESULT: We report a
      33-year-old lady whose headache fulfilled the criteria for HC, but the patient
      developed gastric side effect to indomethacin and did not respond to other
      pharmacological treatments; however, injecting botulinum toxin type A has led to
      complete resolution of all of her symptoms. DISCUSSION: We hypothesize the
      mechanism by which botulinum toxin type A has led to our results through
      reviewing recent functional neuroimaging findings used to understand the
      pathophysiology of different primary headache disorders.

PMID- 23534368
TI  - Palladium-catalyzed diarylmethyl C(sp3)-C(sp2) bond formation: a new coupling
      approach toward triarylmethanes.
AB  - Palladium-catalyzed reductive coupling reactions between N-tosylhydrazones and
      aryl halides lead to the formation of C(sp(3))-C(sp(2)) bonds. This approach
      provides a general route for the synthesis of triarylmethanes.

PMID- 23534369
TI  - Congenital myxoid and pigmented dermatofibrosarcoma protuberans: a case report.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a low-grade, mesenchymal, spindle cell
      tumor. In addition to the classical form characterized by a storiform pattern of
      tumor cells, pigmented (Bednar's tumor) and myxoid variants can be observed.
      Classical DFSP and Bednar's tumor are easily diagnosed. The myxoid variant
      represents a diagnostic challenge. Pigmented and myxoid variants are rare and
      thus far have never been reported in association in congenital DFSP. We came
      across a unique DFSP that was, at the same time, congenital, pigmented, and
      myxoid. The tumor was surgically excised with broad free margins and no
      recurrence. The differential diagnosis with other entities such as giant cell
      fibroblastoma, CD34-positive plaque-like dermal fibroma, superficial plaque-like
      CD34 DFSP, and neurocristic hamartoma is discussed. The recognition of this
      hybrid variant of congenital DFSP is important to avoid under- or overtreatment. 

PMID- 23534370
TI  - Quality of life in patients with cognitive impairment: validation of the Quality
      of Life-Alzheimer's Disease scale in Portugal.
AB  - BACKGROUND: Quality of Life-Alzheimer's Disease (QOL-AD) is a widely used scale
      for the study of quality of life in patients with dementia. The aim of this study
      is the transcultural adaptation and validation of the QOL-AD scale in Portugal.
      METHODS: Translation and transcultural adaptation was performed according to
      state-of-the-art recommendations. For the validation study, 104 patient/caregiver
      pairs were enrolled. Patients had mild cognitive impairment or mild-to-moderate
      dementia (due to Alzheimer's disease or vascular dementia). Participants were
      recruited in a dementia outpatient clinic setting and a long-term care dementia
      ward. An additional comparison group of 22 patients without cognitive impairment,
      and their proxies, was recruited in a family practice outpatient clinic.
      Sociodemographic information on patients and caregivers was obtained.
      Acceptability, reliability, and construct validity were analyzed. RESULTS:
      Internal consistency of the Portuguese version of QOL-AD was good for both
      patient and caregiver report (Cronbach's alpha = 0.867 and 0.858, respectively).
      Construct validity was confirmed by the correlation of patient reported QOL-AD
      with patient geriatric depression scale scores (rho = -0.702, p < 0.001) and
      satisfaction with life scale scores (rho = 0.543, p < 0.001). Caregiver ratings
      were correlated with neuropsychiatric inventory (NPI) total score (rho = -0.404,
      p < 0.001), NPI-distress (rho = -0.346, p < 0.001), and patient Mini-Mental State
      Examination (rho = 0.319, p < 0.01). QOL-AD patient ratings were higher than
      caregiver ratings (p < 0.001). Both patient- and caregiver-rated QOL-AD scores
      were lower in patients with cognitive impairment than in the comparison group
      without cognitive impairment (p < 0.01). CONCLUSIONS: A Portuguese version of QOL
      AD with consistent psychometric properties was obtained and is proposed as a
      useful tool for research and clinical purposes.

PMID- 23534371
TI  - Isolation of meticillin-resistant staphylococci in canine skin infections in Rio
      de Janeiro, Brazil.

PMID- 23534372
TI  - Rotational isomers of N-methyl-N-arylacetamides and their derived enolates:
      implications for asymmetric Hartwig oxindole cyclizations.
AB  - The rotational preferences of N-(2-bromo-4,6-dimethylphenyl)-N-methyl 2
      phenylpropanamide were studied as a model of precursors for Hartwig asymmetric
      oxindole cyclizations. The atropisomers of this compound were separated by flash
      chromatography, and then the enantiomers were resolved and the interconversions
      of the stereocenter and the N-Ar axis were studied. Under thermal conditions, the
      axis is very stable. Under the basic conditions of the Hartwig cyclization, both
      the stereocenter and the chiral axis equilibrate via enolate formation. The N-Ar
      rotation barrier of a 2-phenylacetamide analogue was reduced from 31 kcal mol(-1)
      in the precursor to 17 kcal mol(-1) in the enolate. Reasons for this dramatic
      barrier reduction and implications of both N-Ar and amide C-N rotations for
      Hartwig cyclizations are discussed.

PMID- 23534373
TI  - Study of interaction between NO radicals and Martin's spirosilane by means of IR
      spectroscopy.
AB  - The matrix isolation method is used to record the IR spectrum of C18H8O2F12Si in
      the 4000-500 cm(-1) range. To gain an IR spectrum with a sufficient resolution,
      this technique was used with neon as the dilution medium at 5 K. The generated
      species were characterized by in situ fourier transform infrared (FT-IR)
      spectroscopy. Once the Martin's spirosilane 1 (C18H8O2F12Si) was characterized,
      its reactivity toward NO was investigated under the same experimental conditions
      (i.e., using neon as a dilution medium at 5 K). In this case, the use of neon at
      very low temperature leads to the formation of a chemically inert matrix in which
      the species are trapped and isolated from one another, thus hindering consecutive
      reactions. As a consequence, intermediates can be observed. This approach allowed
      us to characterize the NO adduct, leading to the formation of 1-(NO).
      Concentration effects as well as annealing experiments were carried out. In
      addition to this experimental approach, products were identified by using
      reference spectra. Our results proved that, in the dilute phase, the reaction
      between 1 and NO radicals leads to the formation of an adduct. This stable
      species can further react with NO to form a more stable compound: 1-(NO)2. This
      proves the ability of such species to trap NO.

PMID- 23534374
TI  - Facile access to large-scale, self-assembled, nacre-inspired, high-performance
      materials with tunable nanoscale periodicities.
AB  - Although advances have been reported to mimic the mechanically excellent
      structure of natural nacre, larger-scale applications are still limited due to
      time and energy-intensive preparation pathways. Herein, we demonstrate that
      simple high-shear homogenization of dispersions containing biobased high
      molecular weight sodium carboxymethyl cellulose (700 kg/mol, CMC) and natural
      sodium montmorillonite (MTM), serving as the soft energy-dissipating phase and
      reinforcing platelets, respectively, can be used to prepare large-area and thick
      films with well-aligned hard/soft nacre-mimetic mesostructure. During this
      process, core-shell nanoplatelets with intrinsic hard/soft structure form, which
      then self-assemble into a layered nanocomposite during water removal. The
      nanoscale periodicities of the alternating hard/soft layers can be precisely
      tuned by changing the ratio of CMC to MTM, which allows studying the evolution of
      mechanical properties as a function of the lamellar nanoscale periodicity and
      fractions of hard to soft material. Remarkable mechanical stiffness (25 GPa) and
      strength (320 MPa) can be obtained placing these materials among the top end of
      nacre-inspired materials reported so far. Mechanical homogenization also allows
      direct preparation of concentrated, yet homogeneous, gel-like dispersions of high
      nanoclay content, suited to doctor-blade large-area and thick films with
      essentially the same properties as films cast from dilute dispersions. In terms
      of functional properties, we report high-transparency, shape-persistent fire
      blocking and the ability to surface-pattern via inkjet printing. Considering the
      simple, fully scalable, waterborne preparation pathway, and the use of nature
      based components, we foresee applications as ecofriendly, bioinspired materials
      to promote sustainable engineering materials and novel types of functional
      barrier coatings and substrates.

PMID- 23534375
TI  - Single-pulse underwater laser-induced breakdown spectroscopy with nongated
      detection scheme.
AB  - We investigated spatially resolved emission spectra of Al atoms in a very small
      (~0.1 mm) laser ablation plasma produced by a single long-pulse (~100 ns)
      irradiation of an Al target in water. The spectral feature varied considerably,
      depending on the position to be measured. The density of the plasma periphery was
      low enough to neglect the self-absorption effect, even when resonance lines were
      observed. By properly selecting the position, we successfully obtained well
      resolved spectral lines even without time-gated detection. This suggests that
      time-gating is not necessary anymore in the practical applications of underwater
      laser-induced breakdown spectroscopy when employing spatially resolved detection
      system.

PMID- 23534376
TI  - Quantum yield of charge separation in photosystem II: functional effect of
      changes in the antenna size upon light acclimation.
AB  - We have studied thylakoid membranes of Arabidopsis thaliana acclimated to
      different light conditions and have related protein composition to excitation
      energy transfer and trapping kinetics in Photosystem II (PSII). In high light:
      the plants have reduced amounts of the antenna complexes LHCII and CP24, the
      overall trapping time of PSII is only ~180 ps, and the quantum efficiency reaches
      a value of 91%. In low light: LHCII is upregulated, the PSII lifetime becomes
      ~310 ps, and the efficiency decreases to 84%. This difference is largely caused
      by slower excitation energy migration to the reaction centers in low-light plants
      due to the LHCII trimers that are not part of the C2S2M2 supercomplex. This pool
      of "extra" LHCII normally transfers energy to both photosystems, whereas it
      transfers only to PSII upon far-red light treatment (state 1). It is shown that
      in high light the reduction of LHCII mainly concerns the LHCII-M trimers, while
      the pool of "extra" LHCII remains intact and state transitions continue to occur.
      The obtained values for the efficiency of PSII are compared with the values of
      Fv/Fm, a parameter that is widely used to indicate the PSII quantum efficiency,
      and the observed differences are discussed. 

PMID- 23534377
TI  - Spontaneous high-grade glial intramedullary tumor of the spine in a rhesus
      macaque (Macaca mulatta).
AB  - BACKGROUND: A 4-year-old rhesus macaque presented with acute, progressive paresis
      of the extremities. METHODS: A complete blood count, serum biochemical analysis,
      neurologic exam and necropsy were performed. RESULTS: The clinical,
      histopathological, and immunohistochemical findings confirmed a high-grade
      intramedullary glial tumor of the spinal cord that was most consistent with an
      ependymoma. CONCLUSIONS: We describe a case of a naturally occurring spontaneous
      spinal cord neoplasia in a non-human primate.

PMID- 23534378
TI  - The authors respond.

PMID- 23534379
TI  - Detection of oral bacterial DNA in synovial fluid.
AB  - OBJECTIVES: As periodontal bacteria might be involved in the aetiology of
      rheumatic diseases, we analysed synovial fluid obtained from patients with
      rheumatoid arthritis (RA) and controls for the presence of DNA of Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia,
      Tannerella forsythia, and Treponema denticola. METHODS: In all, 42 patients
      suffering from RA (mean age 53.8 +/- 16.7 years, 40.4% females) and 114 controls
      with no rheumatic diseases (mean age 56.1 +/- 15.2 years, 52.4% females) were
      included. DNA from synovial fluid was isolated by QiaAmp kit (Qiagen, Hilden,
      Germany). Polymerase chain reactions (PCRs) specific for the 16S rRNA genes of
      the above specified bacteria were developed. Subgingival bacterial colonization
      was analysed using micro-Ident((r)) test (HAIN-Diagnostik, Nehren, Germany).
      RESULTS: In patients with RA DNA of P. gingivalis was detected in synovial fluid
      more often than in controls (15.7% versus 3.5%, p = 0.045). More patients than
      controls harboured DNA from P. gingivalis in both, oral plaque and synovial fluid
      (11.9% versus. 0.9%, p = 0.030). Among the patients group the number of missing
      teeth was correlated with the number of joints with movement restrictions caused
      by RA. CONCLUSIONS: DNA of periodontopathogens can be found in synovial fluid and
      oral bacteria may play a role in the pathogenesis of arthritis.

PMID- 23534380
TI  - Extracorporeal photopheresis: a useful therapy for patients with steroid
      refractory acute graft-versus-host disease but not for the prevention of the
      chronic form.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has been used successfully to
      treat severe steroid-refractory acute and chronic graft-versus-host disease
      (aGVHD, cGVHD) since the late 1990s. OBJECTIVES: To evaluate retrospectively the
      efficacy and safety of ECP in patients with aGVHD. We also assessed whether ECP
      may play a role in the prevention of cGVHD. PATIENTS AND METHODS: Nine
      consecutive patients with allografts with aGVHD grade II-III, as defined by
      consensus criteria, and refractory to steroids, were treated with ECP. ECP was
      started at a median interval of 46.3 days (range 10-70) from aGVHD onset.
      Patients were treated initially on two consecutive days (one cycle) at 1-week
      intervals until improvement and then every 2 weeks. Treatment was then tapered
      off individually. To evaluate statistical relationships with outcome after 30, 60
      and 90 days of ECP, all clinical and historical variables of the patients before
      treatment were analysed. RESULTS: All patients survived and responded within 90
      days. The average aGVHD score was 1.72 at aGVHD onset, 2.44 when ECP was started
      and then gradually declined to 0.44 on day 90. At the same time, the average dose
      of methylprednisolone declined from 2.22 mg kg(-1) to 0.27 mg kg(-1) (day 90),
      while the average dose of ciclosporin declined from 2.46 mg kg(-1) to 0.77 mg kg(
      1) (day 90). Six of nine patients showed a complete skin response after 90 days
      of treatment. All patients with liver and gastrointestinal tract involvement had
      complete responses after 90 days, apart from one patient. All our patients
      developed cGVHD, seven of nine while still on maintenance regimen (6-13 months
      after haematopoietic stem cell transplantation, HSCT) and the other two patients
      after suspension of ECP (6 and 9 months after HSCT). CONCLUSIONS: ECP is
      effective in patients with mild to moderate steroid-refractory aGVHD (grade II
      III). On the other hand, ECP did not prevent the development of cGVHD in our
      patients.

PMID- 23534381
TI  - Synthetic, structural, NMR, and computational study of a geminally bis(peri
      substituted) tridentate phosphine and its chalcogenides and transition-metal
      complexes.
AB  - Coupling of two acenaphthene backbones through a phosphorus atom in a geminal
      fashion gives the first geminally bis(peri-substituted) tridentate phosphine 1.
      The rigid nature of the aromatic backbone and overall crowding of the molecule
      result in a rather inflexible ligand, with the three phosphorus atoms forming a
      relatively compact triangular cluster. Phosphine 1 displays restricted dynamics
      on an NMR time scale, which leads to the anisochronicity of all three phosphorus
      nuclei at low temperatures. Strained bis- and tris(sulfides) 2 and 3 and the
      bis(selenide) 4 have been isolated from the reaction of 1 with sulfur and
      selenium, respectively. These chalcogeno derivatives display pronounced in-plane
      and out-of-plane distortions of the aromatic backbones, indicating the limits of
      their angular distortions. In addition, we report metal complexes with
      tetrahedral [(1)Cu(MeCN)][BF4] (5), square planar [(1)PtCl][Cl] (6), trigonal
      bipyramidal [(1)FeCl2] (7), and octahedral fac-[(1)Mo(CO)3] (8) geometries. In
      all of these complexes the tris(phosphine) backbone is distorted, however to a
      significantly smaller extent than that in the mentioned chalcogenides 2-4.
      Complexes 5 and 8 show fluxionality in (31)P and (1)H NMR. All new compounds 1-8
      were fully characterized, and their crystal structures are reported. Conclusions
      from dynamic NMR observations were augmented by DFT calculations.

PMID- 23534383
TI  - Effects of surgical vs. nonsurgical therapy on erectile dysfunction and quality
      of life in obstructive sleep apnea syndrome: a pilot study.
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with erectile
      dysfunction (ED). The improvement of ED after medical therapy including
      continuous positive airway pressure (CPAP) or mandibular advancement devices
      (MADs) is still controversial. Furthermore, the efficacy of surgical treatment
      has been little investigated. AIM: The aim of this nonrandomized prospective
      study was to evaluate the effects of surgical (uvulopalatopharyngoplasty [UPPP])
      and nonsurgical approaches (CPAP and MAD) on ED and quality of life (QOL) in
      OSAS. METHODS: OSAS patients underwent UPPP (N = 30), CPAP (N = 16), or MAD (N =
      10) and completed the Korean versions of the International Index of Erectile
      Function questionnaire (KIIEF-5) and the Calgary Sleep Apnea Quality of Life
      Index (SAQLI) before and after a median of 7 months of treatment (interquartile
      range, 4-15 months). All patients underwent a full-night in-laboratory
      polysomnography at baseline and follow-up. MAIN OUTCOME MEASURE: The main outcome
      measures are the KIIEF-5 and SAQLI scores. RESULTS: CPAP group showed older age,
      higher body mass index, and more severe OSAS than other groups. Apnea-hypopnea
      index and lowest oxygen saturation level improved significantly in all groups,
      but Epworth Sleepiness Scale score decreased significantly in UPPP and MAD
      groups. Significant increase of KIIEF-5 was observed in patients who underwent
      UPPP (P = 0.039, paired t-test), but not in nonsurgical treatment group. All
      groups had the tendency of better QOL after treatment, but statistical
      significance was found only in MAD group. Neck circumference (r = 0.360, P =
      0.006) and KIIEF-5 score (r = -0.484, P < 0.001) at baseline were significantly
      related to the improvement of KIIEF-5. CONCLUSIONS: This study demonstrated that
      ED in OSAS may improve following UPPP. Better disease-specific QOL was observed
      after both surgical and nonsurgical therapies in OSAS. These findings suggest
      that interventions for OSAS can provide the alleviation of ED and increase QOL in
      OSAS patients with ED, especially if they had pronounced complaints of ED and
      wide neck circumferences.

PMID- 23534384
TI  - Genetics research: jumping into the deep end of the pool.
AB  - The publication of the human genome, more than a decade ago, alongside the
      development of high-throughput technologies for DNA sequencing, marked the dawn
      of a new era in genetics. Large genomic projects have been initiated to decipher
      the mysteries hidden within the human genetic code. With the rapidly ever-growing
      amount of genetic information, and the importance of understanding what it all
      means, there is a need to generate an interdisciplinary hub that will connect
      researchers, both experimentalists and bioinformaticians, along with physicians
      and community representatives in order to develop a common genomic language. This
      should lead to an accessible, readable and interpretive human genome with a short
      list of personal actionable items. We will then be able to declare that we are
      moving ever closer to the point at which one's own genome will affect one's
      personal life at a scope beyond our current comprehension.

PMID- 23534382
TI  - Identification of oxidation sites and covalent cross-links in metal catalyzed
      oxidized interferon Beta-1a: potential implications for protein aggregation and
      immunogenicity.
AB  - Oxidation via Cu(2+)/ascorbate of recombinant human interferon beta-1a
      (IFNbeta1a) leads to highly immunogenic aggregates, however it is unknown which
      amino acids are modified and how covalent aggregates are formed. In the present
      work we mapped oxidized and cross-linked amino acid residues in aggregated
      IFNbeta1a, formed via Cu(2+)/ascorbate catalyzed oxidation. Size exclusion
      chromatography (SEC) was used to confirm extensive aggregation of oxidized
      IFNbeta1a. Circular dichroism and intrinsic fluorescence spectroscopy indicated
      substantial loss of secondary and tertiary structure, respectively.
      Derivatization with 4-(aminomethyl)benzenesulfonic acid was used to demonstrate,
      by fluorescence in combination with SEC, the presence of tyrosine (Tyr) oxidation
      products. High performance liquid chromatography coupled to electrospray
      ionization mass spectrometry of reduced, alkylated, and digested protein was
      employed to localize chemical degradation products. Oxidation products of
      methionine, histidine, phenylalanine (Phe), tryptophan, and Tyr residues were
      identified throughout the primary sequence. Covalent cross-links via 1,4- or 1,6
      type addition between primary amines and DOCH (2-amino-3-(3,4-dioxocyclohexa-1,5
      dien-1-yl)propanoic acid, an oxidation product of Phe and Tyr) were detected.
      There was no evidence of disulfide bridge, Schiff base, or dityrosine formation.
      The chemical cross-links identified in this work are most likely responsible for
      the formation of covalent aggregates of IFNbeta1a induced by oxidation, which
      have previously been shown to be highly immunogenic.

PMID- 23534385
TI  - Dietary glycaemic index and glycaemic load in relation to food and nutrient
      intake and indices of body fatness in British children and adolescents.
AB  - The diversity of the associations of dietary glycaemic index (GI) and glycaemic
      load (GL) with dietary intake and body fatness observed in epidemiological
      studies may be partly due to the differences in underlying dietary intake
      patterns. We examined the cross-sectional associations of dietary GI and GL with
      food and nutrient intakes and indices of body fatness in 818 children aged 4-10
      years and 818 adolescents aged 11-18 years in Britain, based on the data from the
      National Diet and Nutrition Survey. Dietary intake was assessed using a 7 d
      weighed dietary record. Overweight was defined as BMI >= 85th percentile of the
      age- and sex-specific British growth reference data. Central obesity was defined
      as waist:height ratio (WHtR) >= 0.5 (adolescents only). Breads, breakfast cereals
      and potatoes were the positive predictive food groups for dietary GI, while dairy
      products, fruit juice, other cereals and fruit were the negative predictors.
      Dietary GL was closely correlated with carbohydrate intake. Dietary GI showed no
      associations with overweight or central obesity. Conversely, dietary GL showed an
      independent association with a higher risk of overweight in children and a higher
      risk of central obesity (but not overweight) in adolescents. However, dietary GI
      and GL were not associated with BMI z-score in children and adolescents or WHtR
      in adolescents. In conclusion, the present study showed that dietary GL was
      independently associated with overweight in children and with central obesity in
      adolescents. Nevertheless, given no associations when body fatness measures were
      treated as continuous variables, the results must be interpreted cautiously.

PMID- 23534387
TI  - Fatal lacosamide poisoning in relation to cardiac conduction impairment and
      cardiovascular failure.

PMID- 23534388
TI  - Composition and diversity of the duodenal mucosa-associated microbiome in
      children with untreated coeliac disease.
AB  - BACKGROUND: Intestinal microbiome may play a role in the pathogenesis of coeliac
      disease (CD). Studies comparing intestinal microbiome in children with and
      without CD are contradictory. AIM: To compare the composition and diversity of
      the duodenal mucosa-associated microbiome in children with untreated CD and
      control children without CD and to identify specific gut bacteria associated with
      CD at diagnosis. METHODS: Total microbiome profile in small bowel biopsies of 42
      children (21 with untreated CD and 21 age-matched controls) were analyzed by
      means of IS-pro, a 16S-23S interspacer (IS) region-based profiling method.
      RESULTS: Both groups showed a similar mucosa-associated microbiome pattern and
      diversity, with high concentrations of the genera Streptococcus, Lactobacillus,
      and Clostridium. CONCLUSION: Mucosa-associated duodenal microbiome composition
      and diversity did not differ between children with untreated CD and control
      children. Duodenal mucosa-associated bacteria do not seem to play an important
      role in the pathogenesis of CD.

PMID- 23534389
TI  - Iconic gesture in normal language and word searching conditions: a case of
      conduction aphasia.
AB  - Although there is a substantive body of research about the language used by
      individuals with aphasia, relatively little is known about their spontaneous
      iconic gesture. A single case study of LT, an individual with conduction aphasia
      indicated qualitative differences between the spontaneous iconic gestures
      produced alongside fluent speech and in tip of the tongue states. The current
      study examined the iconic gestures produced by another individual with conduction
      aphasia, WT, and a group of 11 control participants. Comparisons were made
      between iconic gestures produced alongside normal language and those produced
      alongside word-searching behaviour. Participants recounted the Tweety and
      Sylvester cartoon Canary Row. All gesture produced was analysed qualitatively and
      quantitatively. WT produced more iconic gestures than controls accompanying word
      searching behaviour, whereas he produced a similar frequency of iconic gestures
      to control participants alongside normal language. The iconic gestures produced
      in the two language contexts also differed qualitatively. Frequency of iconic
      gesture production was not affected by limb apraxia. This study suggests that
      there are differences between iconic gestures that are produced alongside normal
      language and those produced alongside word-searching behaviour. Theoretical and
      clinical implications of these findings are discussed.

PMID- 23534386
TI  - CD4 T cells in immunity and immunotherapy of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia, with prevalence
      progressively increasing with aging. Pathological hallmarks of the disease
      include accumulation of amyloid beta-protein (Abeta) peptides and neurofibrillary
      tangles in the brain associated with glial activation and synaptotoxicity. In
      addition, AD involves peripheral and brain endogenous inflammatory processes that
      appear to enhance disease progression. More than a decade ago a new therapeutic
      paradigm emerged for AD, namely the activation of the adaptive immune system
      directly against the self-peptide Abeta, aimed at lowering its accumulation in
      the brain. This was the first time that a brain peptide was used to vaccinate
      human subjects in a manner similar to classic viral or bacterial vaccines. The
      vaccination approach has taken several forms, from initially active to passive
      and then back to modified active vaccines. As the first two approaches to date
      failed to show sufficient efficacy, the last is presently being evaluated in
      ongoing clinical trials. The present review summarizes the immunogenic
      characteristics of Abeta in humans and mice and discusses past, present and
      future Abeta-based immunotherapeutic approaches for AD. We emphasize potential
      pathogenic and beneficial roles of CD4 T cells in light of the pathogenesis and
      the general decline in T-cell responsiveness evident in the disease.

PMID- 23534390
TI  - Inhibition of 12-lipoxygenase reduces platelet activation and prevents their
      mitogenic function.
AB  - The aim of the present study was to investigate the role of 12-lipoxygenase (12
      LOX) on platelet-induced airway smooth muscle cell (ASMC) proliferation. Co
      incubation of platelets and ASMC caused platelet activation as determined by
      morphological changes. Simultaneously, reactive oxygen species (ROS)-generation
      was detected and ASMC proliferation (measured by using the MTS assay) increased
      significantly. Furthermore, we found that the 12-LOX inhibitors cinnamyl-3,4
      dihydroxy-alpha-cyanocinnamate (CDC) and Baicalein prevented platelet activation
      in a co-cultures of platelets and ASMC. The inhibitory effect of CDC and
      Baicalein on platelets was also registered in a pure platelet preparation.
      Specifically, the 12-LOX inhibitors reduced collagen-induced platelet aggregation
      both in the presence and absence of external added fibrinogen. Importantly,
      platelet-induced ASMC proliferation and ROS production generated during the
      platelet/ASMC interaction was significantly inhibited in the presence of 12-LOX
      inhibitors. In conclusion, our findings reveal that 12-LOX is crucial for the
      observed enhancement of ASMC proliferation in co-cultures of platelets and ASMC.
      The present result suggests that 12-LOX activity is important in the initial step
      of platelet/ASMC interaction and platelet activation. Such action of 12-LOX
      represents a potential important mechanism that may contribute to platelet
      induced airway remodelling.

PMID- 23534391
TI  - Enantioselective synthesis of (E)-delta-silyl-anti-homoallylic alcohols via an
      enantiodivergent hydroboration-crotylboration reaction of a racemic
      allenylsilane.
AB  - The enantioselective hydroboration of racemic allenylsilane (+/-)-4 with
      ((d)Ipc)2BH proceeds via enantiodivergent pathways to give vinylborane 11 and
      crotylborane intermediate (S)-E-5. Subsequent crotylboration of aldehyde
      substrates with (S)-E-5 at -78  degrees C provides (E)-delta-silyl-anti
      homoallylic alcohols in 71-89% yield and with 93-96% ee.

PMID- 23534392
TI  - Pulmonary venous flow index as a predictor of pulmonary vascular resistance
      variability in congenital heart disease with increased pulmonary flow: a
      comparative study before and after oxygen inhalation.
AB  - AIMS: There is no definitive and reliable echocardiographic method for estimating
      the pulmonary vascular resistance (PVR) to differentiate persistent vascular
      disease from dynamic pulmonary hypertension. The aim of this study was to analyze
      the relationship between the pulmonary venous blood flow velocity-time integral
      (VTIpv) and PVR. METHODS AND RESULTS: Eighteen patients (10 females; 4 months to
      22 years of age) with congenital heart disease and left to right shunt were
      studied. They underwent complete cardiac catheterization, including measurements
      of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous
      left inferior pulmonary venous flow VTIpv was obtained by Doppler
      echocardiography. The PVR decreased significantly from 5.0 +/- 2.6 W to 2.8 +/-
      2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 +/-
      1.4 to 4.9 +/- 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6
      +/- 4.7 cm to 28.1 +/- 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv
      correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively).
      Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy
      of 83%, a positive predictive value of 92% and a negative predictive value of
      60%. CONCLUSION: The VTIpv correlated well with the PVR. The measurement of this
      index before and after oxygen inhalation may become a useful noninvasive test for
      differentiating persistent vascular disease from dynamic and flow-related
      pulmonary hypertension.

PMID- 23534393
TI  - Feasibility of using biomarkers in blood serum as markers of effect following
      exposure of the lungs to particulate matter air pollution.
AB  - Particulate matter (PM) air pollution has significant cardiopulmonary health
      effects. Serum biomarkers may elucidate the disease mechanisms involved and
      provide a means for biomonitoring exposed populations, thereby enabling accurate
      policy decisions on air quality standards to be made. For this review, research
      investigating association of blood serum biomarkers and exposure to PM was
      identified, finding 26 different biomarkers that were significantly associated
      with exposure. Recent evidence links different effects to different components of
      PM. Future research on biomarkers of effect will need to address exposure by all
      PM size fractions.

PMID- 23534394
TI  - Comparison of in silico models for prediction of mutagenicity.
AB  - Using a dataset with more than 6000 compounds, the performance of eight
      quantitative structure activity relationships (QSAR) models was evaluated:
      ACD/Tox Suite, Absorption, Distribution, Metabolism, Elimination, and Toxicity of
      chemical substances (ADMET) predictor, Derek, Toxicity Estimation Software Tool
      (T.E.S.T.), TOxicity Prediction by Komputer Assisted Technology (TOPKAT),
      Toxtree, CEASAR, and SARpy (SAR in python). In general, the results showed a high
      level of performance. To have a realistic estimate of the predictive ability, the
      results for chemicals inside and outside the training set for each model were
      considered. The effect of applicability domain tools (when available) on the
      prediction accuracy was also evaluated. The predictive tools included QSAR
      models, knowledge-based systems, and a combination of both methods. Models based
      on statistical QSAR methods gave better results.

PMID- 23534395
TI  - Cancer chemoprevention by polyphenols and their potential application as
      nanomedicine.
AB  - Today cancer is a leading cause of death among the developed countries. Its
      highly complex nature makes it difficult to understand as it entails multiple
      cellular physiological systems such as cell signaling and apoptosis. The biggest
      challenges faced by cancer chemoprevention/chemotherapy is maintaining drug
      circulation and avoiding multidrug resistance. Overall there is modest evidence
      regarding the protective effects of nutrients from supplements against a number
      of cancers. Numerous scientific literatures available advocate the use of
      polyphenols for chemoprevention. Some groups have also suggested use of
      combination of nutrients in cancer prevention. However, we have yet to obtain the
      desired results in the line of cancer chemotherapy research. Nanotechnology can
      play a pivotal role in cancer treatment and prevention. Moreover, nanoparticles
      can be modified in various ways to prolong circulation, enhance drug
      localization, increase drug efficacy, and potentially decrease the chances of
      multidrug resistance. In this communication, we will cover the use of various
      polyphenols and nutrients in cancer chemoprevention. The application of
      nanotechnology in this regard will also be included. In view of available reports
      on the potential of nanoparticles, we suggest their usage along with different
      combination of nutrients as cancer chemotherapeutic agents.

PMID- 23534396
TI  - Impaired mitochondrial fatty acid oxidation and insulin resistance in aging:
      novel protective role of glutathione.
AB  - Aging is associated with impaired fasted oxidation of nonesterified fatty acids
      (NEFA) suggesting a mitochondrial defect. Aging is also associated with
      deficiency of glutathione (GSH), an important mitochondrial antioxidant, and with
      insulin resistance. This study tested whether GSH deficiency in aging contributes
      to impaired mitochondrial NEFA oxidation and insulin resistance, and whether GSH
      restoration reverses these defects. Three studies were conducted: (i) in 82-week
      old C57BL/6 mice, the effect of naturally occurring GSH deficiency and its
      restoration on mitochondrial (13) C1 -palmitate oxidation and glucose metabolism
      was compared with 22-week-old C57BL/6 mice; (ii) in 20-week C57BL/6 mice, the
      effect of GSH depletion on mitochondrial oxidation of (13) C1 -palmitate and
      glucose metabolism was studied; (iii) the effect of GSH deficiency and its
      restoration on fasted NEFA oxidation and insulin resistance was studied in GSH
      deficient elderly humans, and compared with GSH-replete young humans. Chronic GSH
      deficiency in old mice and elderly humans was associated with decreased fasted
      mitochondrial NEFA oxidation and insulin resistance, and these defects were
      reversed with GSH restoration. Acute depletion of GSH in young mice resulted in
      lower mitochondrial NEFA oxidation, but did not alter glucose metabolism. These
      data suggest that GSH is a novel regulator of mitochondrial NEFA oxidation and
      insulin resistance in aging. Chronic GSH deficiency promotes impaired NEFA
      oxidation and insulin resistance, and GSH restoration reverses these defects.
      Supplementing diets of elderly humans with cysteine and glycine to correct GSH
      deficiency could provide significant metabolic benefits.

PMID- 23534397
TI  - The impact of actual and perceived disease severity on pre-operative
      psychological well-being and illness behaviour in adult congenital heart disease
      patients.
AB  - OBJECTIVES: The purpose of this study was to investigate whether the objective
      medical parameters related to congenital heart disease and patients' ratings of
      cardiac disease severity were related to psychological well-being and illness
      behaviour during the pre-operative period. METHODS: A total of 143 patients (63
      male patients; 16-73 years old) with congenital heart disease evaluated the
      severity of their cardiac condition using a numerical rating scale ranging from
      0, indicating the least severe condition, to 100, indicating the most severe
      condition. Psychological well-being was assessed using the Psychological General
      Well-Being Index (total score <= 60 indicating severe distress) and illness
      behaviour using the Illness Behavior Questionnaire. RESULTS: Pre-operative
      psychological well-being was not related to the objective medical parameters
      reflecting cardiac disease severity. In contrast, total psychological well-being
      scores correlated significantly with patients' subjective ratings of disease
      severity (p < 0.001). When compared with the reference values from the Italian
      population, the mean scores of the patients on psychological well-being were
      similar. As regards the Illness Behavior Questionnaire, the scores on denial were
      higher and those on hypochondria were lower compared with other hospitalised
      patients. CONCLUSIONS: This study shows that the perception of cardiac disease
      severity, and not the medical parameters in congenital heart disease, is related
      to the patients' pre-operative psychological state. Thus, more importance needs
      to be given to assessing the patients' pre-operative perception and psychological
      state independently of cardiac severity. Targeted interventions with regard to
      the cardiac condition are recommended.

PMID- 23534398
TI  - 'Surviving the sting': the use of solicited diaries in children and young people
      with oral mucosal disease.
AB  - BACKGROUND: Chronic oral mucosal conditions, including oral ulcers, commonly
      affect children and young people and are capable of significant pain and
      morbidity. Little is known about patient perception of paediatric oral medicine
      services offered in relation to these conditions. The concept of a diary is
      increasingly recognised as a valuable way to capture patient events and
      perspective in healthcare research. AIM OF THE PAPER: This article provides the
      background to the use of solicited diaries as a method of accessing the
      perspective of children and young people and describes a service evaluation that
      aimed to explore the experiences of young people with chronic oral ulcers
      attending the paediatric oral medicine clinic in a UK Dental Hospital. RESULTS:
      Chronic oral ulcers were found to significantly impact on a variety of physical
      and psychosocial aspects of young people's lives. Overall, feedback regarding the
      specialist service was positive but suggestions were made for improvements.
      CONCLUSION: This article reviews the use of the solicited diary within healthcare
      research. It also illustrates the value of the diary in exploration of children
      and young people's perspective on their chronic oral mucosal disease. In
      addition, a need for further research in this area has been highlighted.

PMID- 23534399
TI  - Topological investigation of glucosyltransferase V in Shigella flexneri using the
      substituted cysteine accessibility method.
AB  - Modification of the lipopolysaccharide O-antigen of Shigella converts the
      serotype, which is significant as acquired immune responses are serotype
      specific. Glucosyltransferases (Gtrs) modify the O-antigen by the addition of
      glucosyl-groups; however the precise mechanism of O-antigen modification is not
      fully understood. This study aims to substantiate inferences made on the GtrV
      topological structure using the substituted cysteine accessibility method (SCAM).
      Twenty-one amino acid residues were tested to clarify three features of GtrV: the
      extramembrane regions, a proposed reentrant loop, and a membrane border region.
      Overall, the results agreed with a previous topology proposed for GtrV. The
      topology of GtrV consists of 11 extramembrane regions with a cytoplasmic N
      terminus, periplasmic C-terminus and 9 transmembrane (TM) helices. The existence
      of a reentrant loop between TM helices IV and V was verified, and the cytoplasmic
      membrane border region of TM helix II was examined in depth.

PMID- 23534400
TI  - Low-temperature metal-oxide thin-film transistors formed by directly
      photopatternable and combustible solution synthesis.
AB  - We investigated the formation of ultraviolet (UV)-assisted directly patternable
      solution-processed oxide semiconductor films and successfully fabricated thin
      film transistors (TFTs) based on these films. An InGaZnO (IGZO) solution that was
      modified chemically with benzoylacetone (BzAc), whose chelate rings decomposed
      via a pi-pi* transition as result of UV irradiation, was used for the direct
      patterning. A TFT was fabricated using the directly patterned IGZO film, and it
      had better electrical characteristics than those of conventional photoresist (PR)
      patterned TFTs. In addition, the nitric acid (HNO3) and acetylacetone (AcAc)
      modified In2O3 (NAc-In2O3) solution exhibited both strong UV absorption and high
      exothermic reaction. This method not only resulted in the formation of a low
      energy path because of the combustion of the chemically modified metal-oxide
      solution but also allowed for photoreaction-induced direct patterning at low
      temperatures.

PMID- 23534401
TI  - Esophageal motor responses to increasing adjustment of an implanted gastric band.
AB  - BACKGROUND: The adjustable gastric band is an effective surgical treatment to
      induce weight loss in patients with morbid obesity. We aimed to assess the
      effects of band placement and stepwise adjustment on esophageal motility, using
      high-resolution manometry (HRM). METHODS: Patients underwent esophageal HRM
      before and 6 weeks after gastric band placement. During postoperative assessment,
      HRM was combined with intraband pressure measurement at increasing filling
      volumes. KEY RESULTS: In total, 15 patients were studied. Mean DCI (+/-SD)
      decreased from 1085.3 +/- 1064.1 mmHg s(-1)  cm(-1) before to 507 +/- 347.2 mmHg
      s(-1)  cm(-1) (P = 0.015) after band placement, mean IBP from 10.7 +/- 1.7 mmHg
      to 7.7 +/- 1.6 mmHg (P = 0.01). Stepwise band adjustment from 1 to 8 mL had an
      immediate and profound effect on swallow-induced esophageal contractions: DCI
      increased from 766 +/- 590.4 to 7231 +/- 6298.1 mmHg s(-1)  cm(-1) , IBP from 4.3
      mmHg to 31.1 +/- 17.3 mmHg, and intraband pressure increased from -109.1 +/- 60.6
      mmHg to 150.2 +/- 65 mmHg. During band filling with volumes >5 mL, upward
      displacement of the LES was observed, indicative of shortening of the esophagus;
      the distance between the UES and LES decreased from 23.5 +/- 1.3 cm at 0 mL to
      19.9 +/- 2 cm at 8 mL. CONCLUSIONS & INFERENCES: Stepwise gastric band adjustment
      leads to immediate enforcement of esophageal peristalsis associated with an
      increase in intrabolus pressure and with pronounced esophageal shortening.
      Subjects who lack these responses to outflow obstruction may be more prone to
      dysphagia after band placement.

PMID- 23534402
TI  - Affinity capture of biotinylated proteins at acidic conditions to facilitate
      hydrogen/deuterium exchange mass spectrometry analysis of multimeric protein
      complexes.
AB  - Characterization of conformational and dynamic changes associated with protein
      interactions can be done by hydrogen/deuterium exchange mass spectrometry (HDX
      MS) by comparing the deuterium uptake in the bound and unbound state of the
      proteins. Investigation of local hydrogen/deuterium exchange in heteromultimeric
      protein complexes poses a challenge for the method due to the increased
      complexity of the mixture of peptides originating from all interaction partners
      in the complex. Previously, interference of peptides from one interaction partner
      has been removed by immobilizing the intact protein on beads prior to the HDX-MS
      experiment. However, when studying protein complexes of more than two proteins,
      immobilization can possibly introduce steric limitations to the interactions.
      Here, we present a method based on the high affinity biotin-streptavidin
      interaction that allows selective capture of biotinylated proteins even under the
      extreme conditions for hydrogen/deuterium exchange quenching i.e. pH 2.5 and 0 
      degrees C. This biotin-streptavidin capture strategy allows hydrogen/deuterium
      exchange to occur in proteins in solution and enables characterization of
      specific proteins in heteromultimeric protein complexes without interference of
      peptides originating from other interaction partners in the complex. The biotin
      streptavidin strategy has been successfully implemented in a model system with
      two recombinant monoclonal antibodies that target nonoverlapping epitopes on the
      human epidermal growth factor receptor (EGFR). We present a workflow for
      biotinylation and characterization of recombinant antibodies and demonstrate
      affinity capture of biotinylated antibodies under hydrogen/deuterium exchange
      quench conditions by the biotin-streptavidin strategy. 

PMID- 23534403
TI  - Extended Huckel theory for carbon nanotubes: band structure and transport
      properties.
AB  - Extended Huckel theory (EHT) is a well established method for the description of
      the electronic structure of molecules and solids. In this article, we present a
      set of extended Huckel parameters for carbon nanotubes (CNTs), obtained by
      fitting the ab initio band structure of the (6,0) CNT. The new parameters are
      highly transferable to different types of CNTs. To demonstrate the versatility of
      the approach, we perform self-consistent EHT-based electron transport
      calculations for finite length CNTs with metal electrodes.

PMID- 23534404
TI  - Ultrafast proton shuttling in Psammocora cyan fluorescent protein.
AB  - Cyan, green, yellow, and red fluorescent proteins (FPs) homologous to green
      fluorescent protein (GFP) are used extensively as model systems to study
      fundamental processes in photobiology, such as the capture of light energy by
      protein-embedded chromophores, color tuning by the protein matrix, energy
      conversion by Forster resonance energy transfer (FRET), and excited-state proton
      transfer (ESPT) reactions. Recently, a novel cyan fluorescent protein (CFP)
      termed psamFP488 was isolated from the genus Psammocora of reef building corals.
      Within the cyan color class, psamFP488 is unusual because it exhibits a
      significantly extended Stokes shift. Here, we applied ultrafast transient
      absorption and pump-dump-probe spectroscopy to investigate the mechanistic basis
      of psamFP488 fluorescence, complemented with fluorescence quantum yield and
      dynamic light scattering measurements. Transient absorption spectroscopy
      indicated that, upon excitation at 410 nm, the stimulated cyan emission rises in
      170 fs. With pump-dump-probe spectroscopy, we observe a very short-lived (110 fs)
      ground-state intermediate that we assign to the deprotonated, anionic
      chromophore. In addition, a minor fraction (14%) decays with 3.5 ps to the ground
      state. Structural analysis of homologous proteins indicates that Glu-167 is
      likely positioned in sufficiently close vicinity to the chromophore to act as a
      proton acceptor. Our findings support a model where unusually fast ESPT from the
      neutral chromophore to Glu-167 with a time constant of 170 fs and resulting
      emission from the anionic chromophore forms the basis of the large psamFP488
      Stokes shift. When dumped to the ground state, the proton on neutral Glu is very
      rapidly shuttled back to the anionic chromophore in 110 fs. Proton shuttling in
      excited and ground states is a factor of 20-4000 faster than in GFP, which
      probably results from a favorable hydrogen-bonding geometry between the
      chromophore phenolic oxygen and the glutamate acceptor, possibly involving a
      short hydrogen bond. At any time in the reaction, the proton is localized on
      either the chromophore or Glu-167, which implies that most likely no low-barrier
      hydrogen bond exists between these molecular groups. This work supports the
      notion that proton transfer in biological systems, be it in an electronic excited
      or ground state, can be an intrinsically fast process that occurs on a 100 fs
      time scale. PsamFP488 represents an attractive model system that poses an
      ultrafast proton transfer regime in discrete steps. It constitutes a valuable
      model system in addition to wild type GFP, where proton transfer is relatively
      slow, and the S65T/H148D GFP mutant, where the effects of low-barrier hydrogen
      bonds dominate. 

PMID- 23534405
TI  - Transplantation and host immune response to Toxoplasma gondii.

PMID- 23534406
TI  - TLR2 down-regulates FcepsilonRI and its transcription factor PU.1 in human
      Langerhans cells.
AB  - BACKGROUND: Epidermal Langerhans cells (LC) expressing the high-affinity receptor
      for IgE (FcepsilonRI) play a key role in atopic dermatitis (AD). AD skin is
      highly colonized with Staphylococcus aureus (S.a.), which are sensed by Toll-like
      receptor 2 (TLR2). We hypothesized that TLR2 may impact on the expression of
      FcepsilonRI on LC. OBJECTIVES: To study a putative impact of TLR2 signaling on
      FcepsilonRI, we analyzed FcepsilonRI and known transcription factors of the
      receptor after ligand binding to TLR2. METHODS: We generated LC from CD34(+)
      progenitors in vitro (CD34LC) expressing FcepsilonRI and TLR2 as well as its
      partners TLR1 and TLR6. The expression of FcepsilonRI and known transcription
      factors of the receptor was analyzed on the protein and RNA level by flow
      cytometry, Western blotting, and real-time PCR. RESULTS: For CD34LC from 123
      donors, we observed a high heterogeneity in FcepsilonRI surface expression
      correlating with mRNA level of its alpha-chain. Stimulation of TLR1/2 or TLR2/6
      dramatically down-regulated FcepsilonRI on protein and mRNA level of both alpha-
      and gamma-chain. Further analysis of putative transcription factors for FCER1A
      revealed the lack of GATA1 in CD34LC, weak expression of ELF1 and YY1, and high
      expression of PU.1. While ELF1 and YY1 appeared to be little affected by TLR2
      engagement, PU.1 was significantly down-regulated. CONCLUSIONS: Taken together,
      our findings show that in human, LC ligation of TLR2 by S.a.-derived products
      down-regulates FcepsilonRI and its transcription factor PU.1, thus suggesting
      that FcepsilonRI is controlled by PU.1 in these cells.

PMID- 23534407
TI  - Reciprocal pathways between American and Chinese early adolescents' sense of
      responsibility and disclosure to parents.
AB  - This research examined the reciprocal pathways between youth's sense of
      responsibility to parents and disclosure to them during early adolescence in the
      United States and China. Four times over the seventh and eighth grades, 825
      American and Chinese youth (M(age) = 12.73 years) reported on their sense of
      responsibility to parents and disclosure of everyday activities to them.
      Autoregressive latent trajectory models revealed that the more youth felt
      responsible to parents, the more they subsequently disclosed to them in both the
      United States and China. The reverse was also true: The more youth disclosed to
      parents, the more responsible they felt to them over time. The strength of these
      reciprocal pathways increased as youth progressed through early adolescence.

PMID- 23534408
TI  - L-tyrosinatonickel(II) complex: synthesis and structural, spectroscopic,
      magnetic, and biological properties of 2{[Ni(L-Tyr)2(bpy)]}.3H2O.CH3OH.
AB  - The complex 2{[Ni(L-Tyr)2(bpy)]}.3H2O.CH3OH [1, where L-Tyr = L-tyrosine; bpy =
      2,2'-bipyridine (2,2'-bpy)] was obtained in crystalline form and characterized by
      X-ray and spectroscopic (FT-IR, NIR-vis-UV, and HFEPR) and magnetic methods. The
      complex crystallized in the hexagonal system with a = b = 12.8116(18) A, c =
      30.035(6) A, and space group P3221. The six-coordination sphere around the Ni(2+)
      ion is formed by two N and two O L-tyrosinato atoms and completed by two N atoms
      of the 2,2'-bpy molecule. Neighboring [Ni(L-Tyr)2(bpy)] units are joined via weak
      hydrogen bonds, which create a helical polymeric chain. The coordinated atoms
      form a strongly distorted cis-NiN2N2'O2 octahedral chromophore. The solid-state
      electronic spectrum of complex 1 was analyzed assuming D2h symmetry, and the
      observed bands were assigned to (3)B1g -> (3)Ag, (3)B1g -> (3)B3g, (3)B1g ->
      (3)B2g, (3)B1g -> (3)B3g, (3)B1g -> (3)B1g, and (3)B1g -> (3)B2g transitions for
      the I and II d-d bands, respectively. The crystal-field parameters found for D2h
      symmetry are Dq = 1066 cm(-1), Ds = 617 cm(-1), Dt = -93 cm(-1), B22 = 7000 cm(
      1), and Racah B = 812 cm(-1). Magnetic studies revealed the occurrence of
      hydrogen-bonded metal pairs. The spin Hamiltonian parameters D = -3.262 cm(-1)
      and E = -0.1094 cm(-1), determined from high-field, high-frequency electron
      paramagnetic resonance spectra, together with a weak antiferromagnetic exchange
      parameter J = -0.477 cm(-1), allowed us to reproduce the powder magnetic
      susceptibility and field-dependent magnetization of the complex. The biological
      activity of 1 has been tested by using the Fusarium solani, Penicillium
      verrucosum, and Aspergillus flavus fungi strains and Escherichia coli,
      Pseudomonas fluorescens, Serratia marcescens, and Bacillus subtilis bacterial
      strains.

PMID- 23534409
TI  - Molecular targets in the discovery and development of novel antimetastatic
      agents: current progress and future prospects.
AB  - Tumour invasion and metastasis have been recognized as major causal factors in
      the morbidity and mortality among cancer patients. Many advances in the knowledge
      of cancer metastasis have yielded an impressive array of attractive drug targets,
      including enzymes, receptors and multiple signalling pathways. The present review
      summarizes the molecular pathogenesis of metastasis and the identification of
      novel molecular targets used in the discovery of antimetastatic agents. Several
      promising targets have been highlighted, including receptor tyrosine kinases,
      effector molecules involved in angiogenesis, matrix metalloproteinases (MMPs),
      urokinase plasminogen activator, adhesion molecules and their receptors,
      signalling pathways (e.g. phosphatidylinositol 3-kinase, phospholipase Cgamma1,
      mitogen-activated protein kinases, c-Src kinase, c-Met kinases and heat shock
      protein. The discovery and development of potential novel therapeutics for each
      of the targets are also discussed in this review. Among these, the most promising
      agents that have shown remarkable clinical outcome are anti-angiogenic agents
      (e.g. bevacizumab). Newer agents, such as c-Met kinase inhibitors, are still
      undergoing preclinical studies and are yet to have their clinical efficacy
      proven. Some therapeutics, such as first-generation MMP inhibitors (MMPIs; e.g.
      marimastat) and more selective versions of them (e.g. prinomastat, tanomastat),
      have undergone clinical trials. Unfortunately, these drugs produced serious
      adverse effects that led to the premature termination of their development. In
      the future, third-generation MMPIs and inhibitors of signalling pathways and
      adhesion molecules could form valuable novel classes of drugs in the anticancer
      armamentarium to combat metastasis.

PMID- 23534410
TI  - Polyarginine molecular weight determines transfection efficiency of calcium
      condensed complexes.
AB  - Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte
      complexes as a means to enhance the transfection efficiency of plasmid DNA
      (pDNA). Increasing the molecular weight of CPPs often enhances gene expression
      but poses a risk of increased cytotoxicity and immunogenicity compared to low
      molecular weight CCPs. Conversely, low molecular weight CPPs typically have low
      transfection efficiency due to large complex size. Complexes made using low
      molecular weight CPPs were found to be condensed to a small size by adding
      calcium. In this study, complexes of low molecular weight polyarginine and pDNA
      were condensed with calcium. These complexes showed high transfection efficiency
      and low cytotoxicity in A549 carcinomic human alveolar basal epithelial cells.
      The relationships between transfection efficiency and polyarginine size (5, 7, 9,
      or 11 amino acids), polyarginine/pDNA charge ratios, and calcium concentrations
      were studied. Polyarginine 7 was significantly more effective than other
      polyarginines under most formulation conditions, suggesting a link between cell
      penetration ability and transfection efficiency.

PMID- 23534412
TI  - Antithrombotic activity of a newly synthesized coumarin derivative 3-(5-hydroxy
      2,2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)
      propionylamino]-ethyl}-propionamide.
AB  - Anti-platelet therapy is a useful strategy to prevent acute thromboembolic artery
      occlusions. This study was designed to assess the efficacy of seselin derivatives
      against murine pulmonary thromboembolism, bleeding time, platelet activation and
      thrombosis. Administration of C3 (16 mg/kg) offered 70% protection against
      collagen- and epinephrine-induced pulmonary thromboembolism and 30% protection
      against arachidonic acid-induced death in mice, without adversely affecting
      bleeding time. No significant difference was observed by C3 in ferric chloride
      induced arterial thrombosis in rats. Significant reduction in thrombus weight was
      observed in arteriovenous shunt model. In rat PRP, C3 reduced ADP and collagen
      induced platelet aggregation. In chronic hamster model of dyslipidemia,
      administration of C3 (16 mg/kg p.o. for 90 days) had no effect on plasma lipids,
      vasoreactivity and platelet adhesion. C3 fed hamsters showed reduced whole-blood
      aggregation response to ADP and collagen compared to HC-fed hamsters. In
      addition, C3 augmented thrombin time; however, time to occlusion was not
      increased. These results convincingly demonstrated that C3 is a novel molecule
      that reduces the risk of thrombosis and alleviates prothrombotic state associated
      with hyperlipidemia without any adverse effect on bleeding time. The high
      benefit/risk ratio of this compound makes it a suitable candidate for future
      valid studies.

PMID- 23534411
TI  - Synthesis and biological evaluation of tricyclic guanidine analogues of
      batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and
      anti-HIV activities.
AB  - Fifty analogues of batzelladine K were synthesized and evaluated for in vitro
      antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani),
      antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities.
      Analogues 14h and 20l exhibited potential antimalarial activity against
      chloroquine-sensitive D6 strain with IC(50) 1.25 and 0.88 MUM and chloroquine
      resistant W2 strain with IC(50) 1.64 and 1.07 MUM, respectively. Analogues 12c
      and 14c having nonyl substitution showed the most potent antileishmanial activity
      with IC(50) 2.39 and 2.78 MUM and IC(90) 11.27 and 12.76 MUM, respectively. Three
      analogues 12c, 14c, and 14i were the most active against various pathogenic
      bacteria and fungi with IC(50) < 3.02 MUM and MIC/MBC/MFC <6 MUM. Analogue 20l
      having pentyl and methyl substituents on tricycle showed promising activities
      against all pathogens. However, none was found active against HIV-1. Our study
      demonstrated that the tricyclic guanidine compounds provide new structural class
      for broad spectrum activity.

PMID- 23534413
TI  - Virtual and in vitro bioassay screening of phytochemical inhibitors from
      flavonoids and isoflavones against xanthine oxidase and cyclooxygenase-2 for gout
      treatment.
AB  - Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat
      the complex pathogenesis of gout, a metabolic disease that results from an
      inflammation of the joints caused by precipitation of uric acid. We seek to
      discover novel phytochemicals that could treat gout, by targeting the xanthine
      oxidase and cyclooxygenase-2 enzymes. In this study, we report the screening of
      nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092
      flavonoids) using the IGEMDOCK software tool against the xanthine oxidase and
      cyclooxygenase-2 3D protein structures. Each compound was also evaluated by an in
      vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase-2.
      Myricetin and luteolin were found to be the potential dual inhibitors of xanthine
      oxidase and cyclooxygenase-2 as demonstrated by IC(50): 62.7 and 3.29 MUg/mL
      (xanthine oxidase)/70.8 and 16.38 MUg/mL (cyclooxygenase-2), respectively. In
      addition, structure-activity relationships and other important factors of the
      flavonoids binding to the active site of xanthine oxidase and cyclooxygenase-2
      were discussed, which is expected for further rational drug design.

PMID- 23534414
TI  - The usefulness of intermediate products of plum processing for alcoholic
      fermentation and chemical composition of the obtained distillates.
AB  - In this study, an evaluation of intermediate products of plum processing as
      potential raw materials for distillates production was performed. Effects of
      composition of mashes on ethanol yield, chemical composition and taste, and
      flavor of the obtained spirits were determined. The obtained results showed that
      spontaneous fermentations of the tested products of plum processing with native
      microflora of raisins resulted in lower ethanol yields, compared to the ones
      fermented with wine yeast Saccharomyces bayanus. The supplementation of mashes
      with 120 g/L of sucrose caused an increase in ethanol contents from 6.2 +/- 0.2 /
      6.5 +/- 0.2% v/v in reference mashes (without sucrose addition, fermented with S.
      bayanus) to ca. 10.3 +/- 0.3% v/v, where its highest yields amounted to 94.7 +/-
      2.9 / 95.6 +/- 2.9% of theoretical capacity, without negative changes in raw
      material originality of distillates. The concentrations of volatile compounds in
      the obtained distillates exceeding 2000 mg/L alcohol 100% v/v and low content of
      methanol and hydrocyanic acid, as well as their good taste and aroma make the
      examined products of plum processing be very attractive raw materials for the
      plum distillates production.

PMID- 23534415
TI  - Study of oxidative, enzymatic mitochondrial respiratory chain function and
      apoptosis in perinatally HIV-infected pediatric patients.
AB  - Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected
      pediatric patients has been scarcely investigated. Limited data are available
      about HIV or antiretroviral (ARV)-mediated mitochondrial damage in this
      population group, specifically, regarding oxygen consumption and apoptosis
      approach. We aimed to elucidate whether a given mitochondrial DNA depletion is
      reflected at downstream levels, to gain insight on the pathology of HIV and
      highly active antiretroviral therapy (HAART) in perinatally HIV-infected
      pediatric patients. We studied 10 healthy control participants and 20 perinatally
      HIV-infected pediatric patients (10 under ARV treatment and 10 off treatment). We
      determined mitochondrial mass, subunits II and IV of complex IV, global and
      specific mitochondrial enzymatic and oxidative activities, and apoptosis from
      peripheral blood mononuclear cells. Global oxygen consumption was significantly
      compromised in HIV-infected untreated patients, compared to the control group
      (0.76 +/- 0.01 versus 1.59 +/- 0.15; P = 0.014). Apoptosis showed a trend to
      increase in untreated patients as well. The overall complex (C) CI-III-IV
      activity of the mitochondrial respiratory chain (MRC) was significantly decreased
      in HIV-infected treated patients with respect to the control group (1.52 +/- 0.38
      versus 6.38 +/- 1.53; P = 0.02). No statistically significant differences were
      found between untreated and HAART-treated patients. These findings suggest the
      pathogenic role of both HIV and HAART in mitochondrial dysfunction in vertical
      infection. The abnormalities in mitochondrial genome may be downstream reflected
      through a global alteration of the MRC. Mitochondrial impairment associated with
      HIV and HAART was generalized, rather than localized, in this series of
      perinatally HIV-infected patients.

PMID- 23534416
TI  - The effects of patient characteristics and geographical region on hospitalization
      in patients with type 2 diabetes.
AB  - AIMS: The ADVANCE trial recruited participants from 20 countries worldwide. We
      analyse here regional variations and causes of hospitalization for people with
      Type 2 diabetes from Asia, Established Market Economies and Eastern Europe.
      METHODS: A cohort analysis examining the effects of region on causes of first
      hospitalization, and the association of participant characteristics on all-cause
      first hospitalization across regions, using multivariable (adjusted for clinical,
      physiological, behavioural and socio-demographic factors) Cox models. RESULTS: Of
      11 140 individuals (6407 men), all-cause hospitalization rates were highest in
      Established Market Economies, followed by Eastern Europe then Asia. Eastern
      Europe had rates of hospitalization for diabetic causes four times greater than
      Established Market Economies [multivariable-adjusted hazard ratio 4.02 (95% CI
      2.86-5.63)]. There were no significant regional variations in hospitalization
      rates for cardiovascular disease (P = 0.534), but much lower rates for
      musculoskeletal and non-specific causes in Eastern Europe [multivariable-adjusted
      hazard ratio 0.44 (95% CI 0.32-0.60) and 0.19 (95% CI 0.12-0.29)] and Asia
      [hazard ratio 0.21 (95% CI 0.16-0.29) and 0.09 (95% CI 0.06-0.14)] compared with
      Established Market Economies. In all regions, participants hospitalized for any
      cause were more likely to be older, male, hypertensive, smokers, have higher
      glycated haemoglobin and a history of macrovascular or macrovascular disease.
      CONCLUSIONS: Across three markedly different regions of the world, regional rates
      and causes of hospitalization varied widely in patients with Type 2 diabetes.
      Adjustment for a range of patient characteristics did not explain these regional
      differences in hospitalization, which appear to be attributable to health system
      factors.

PMID- 23534417
TI  - Prospective study of changes in sugar-sweetened beverage consumption and the
      incidence of the metabolic syndrome and its components: the SUN cohort.
AB  - The incidence of the metabolic syndrome (MetS) is increasing and lifestyle
      behaviours may play a role. The aim of the present study was to prospectively
      assess the association between changes in the consumption of sugar-sweetened
      beverages (SSB) and the incidence of the MetS and its components in a Spanish
      cohort of university graduates. We included 8157 participants initially free of
      the MetS and followed up during at least 6 years. SSB consumption was collected
      by a FFQ previously validated in Spain. The change in SSB consumption was
      calculated as the difference between SSB consumption at a 6-year follow-up and
      baseline consumption. The MetS was defined according to the International
      Diabetes Federation and the American Heart Association/National Heart, Lung, and
      Blood Institute's new definition of the MetS that had harmonised previous
      definitions. The associations between changes in SSB intake and the MetS were
      examined using multiple logistic regression. We observed 361 incident cases of
      the MetS. Participants who increased their consumption of SSB (upper v. lower
      quintile) had a significantly higher risk of developing the MetS (adjusted OR
      2.2, 95 % CI 1.4, 3.5; P for trend = 0.003). Similarly, they presented a
      significantly higher risk of developing high blood pressure (adjusted OR 1.6, 95
      % CI 1.3, 2.1), central obesity (adjusted OR 2.3, 95 % CI 1.9, 2.7),
      hypertriacylglycerolaemia (adjusted OR 1.7, 95 % CI 1.1, 2.6) or impaired fasting
      glucose (adjusted OR 1.6, 95 % CI 1.1, 2.2). In conclusion, an increase in SSB
      consumption was associated with a higher risk of developing the MetS and other
      metabolic disorders after 6 years of follow-up in a Mediterranean cohort of
      university graduates.

PMID- 23534418
TI  - NHC-catalyzed reaction of enals with hydroxy chalcones: diastereoselective
      synthesis of functionalized coumarins.
AB  - The N-heterocyclic carbene-catalyzed annulation of enals with 2'-hydroxy
      chalcones afford cyclopentane-fused coumarin derivatives with an excellent level
      of diastereocontrol. The reaction tolerates a broad range of functional groups;
      25 examples are given, and a preliminary mechanistic investigation is provided.

PMID- 23534419
TI  - Is the tiered immunogenicity testing of biologics the adequate approach in
      preclinical development?

PMID- 23534421
TI  - Critique: measuring hydrogen stable isotope abundance of proteins to infer
      origins of wildlife, food and people.
AB  - Measurement of the relative abundance of (2)H (expressed in delta(2)H values) in
      tissues of plants, wildlife and people has evolved into a powerful forensic tool.
      The approach is based on the strong linkage between spatial patterns of delta(2)H
      values in precipitation at local and continental scales, and the tissues of
      plants and animals produced on these 'isoscapes'. Unfortunately, despite this
      exciting potential, difficulties inherent in the measurement of delta(2)H values
      in complex organic materials such as proteins, as well as the accuracy of such
      measurements, and a reluctance to adopt strict quality assurance/QC approaches to
      address challenges associated with these measurements, has clearly limited this
      potential. These challenges are entirely avoidable and techniques now exist for
      the routine reliable measurement of delta(2)H values in materials of forensic
      interest that will allow completely comparable data among laboratories.

PMID- 23534422
TI  - The metabolism of anabolic-androgenic steroids in the greyhound.
AB  - BACKGROUND: Effective control of the use of anabolic-androgenic steroids (AASs)
      in animal sports is essential in order to ensure both animal welfare and
      integrity. In order to better police their use in Australian and New Zealand
      greyhound racing, thorough metabolic studies have been carried out on a range of
      registered human and veterinary AASs available in the region. RESULTS: Canine
      metabolic data are presented for the AASs boldenone, danazol, ethylestrenol,
      mesterolone, methandriol, nandrolone and norethandrolone. The principal Phase I
      metabolic processes observed were the reduction of A-ring unsaturations and/or 3
      ketones with either 3alpha,5beta- or 3beta,5alpha-stereochemistry, the oxidation
      of secondary 17beta-hydroxyl groups and 16alpha-hydroxylation. The Phase II beta
      glucuronylation of sterol metabolites was extensive. CONCLUSION: The presented
      data have enabled the effective analysis of AASs and their metabolites in
      competition greyhound urine samples.

PMID- 23534423
TI  - Analysis of human saliva metabolome by direct immersion solid-phase
      microextraction LC and benchtop orbitrap MS.
AB  - BACKGROUND: Saliva samples collected from one 58 year old male and one 35 year
      old female during 7 days of fasting were analyzed by direct immersion of both C18
      and mixed-mode biocompatible solid-phase microextraction fibers, in combination
      with a LC-MS method using a benchtop orbitrap instrument in both positive and
      negative ionization modes, in order to evaluate the difference in terms of
      metabolite coverage. RESULTS: The mixed-mode coating provided better results,
      with the simultaneous extraction of a higher number of both hydrophilic and
      hydrophobic metabolites. The ability of detected features to distinguish
      differences between the individuals and changes in saliva metabolome induced by
      diet was also demonstrated. CONCLUSION: Saliva may be useful for medical
      diagnostics as it is non-invasive. The use of biocompatible solid-phase
      microextraction fibers can play an important role as an alternative sample
      preparation method for untargeted LC-MS metabolomics studies on human saliva
      because it provides simultaneous extraction of metabolites with a wide range of
      polarity, thus allowing the detection of changes in metabolic pathways with
      unsupervised statistical analyses.

PMID- 23534424
TI  - LC-MS/MS approaches for the assay of bis-quaternary pyridinium oximes used as
      AChE reactivators in biological matrices.
AB  - BACKGROUND: Extreme efforts are made for the structural diversification of oximes
      used as AChE reactivators. Co-administration of different oximes should also be
      considered as a solution in therapy. Consequently, development of selective
      assays of oximes in biological matrices is of major importance. RESULTS: Three
      chromatographic separation mechanisms were evaluated: hydrophilic-interaction LC;
      mixed reversed-phase/cation exchange (DUET); and reversed-phase ion pairing based
      on per-fluorinated agents. MS was used to identify and quantify oximes.
      Alternative preparation of whole blood and plasma samples were used based on
      protein precipitation through addition of acetonitrile or ionic liquids. Quality
      characteristics of the proposed analytical approaches are discussed. CONCLUSION:
      The reversed-phase ion pairing based on per-fluorinated agents chromatographic
      separation mechanism and positive ESI-MS/MS detection produced the best results
      for the assay of bis-quaternary pyridinium oximes. LLOQ in the tenths of nanogram
      per milliliter range are achievable.

PMID- 23534425
TI  - A case study of validation and sample analysis for the determination of
      zotarolimus in various tissues.
AB  - BACKGROUND: Biodistribution of drug and drug candidates offers critical
      information regarding drug disposition in target and nontarget tissues.
      Concentrations of therapeutic agents in target tissue provide the foundation for
      efficacy, while concentrations in nontarget tissue pose potential safety risks.
      Analysis of tissue samples can sometimes provide important information during the
      development of a drug candidate, especially at early stages when radio labeled
      drug material is not readily available. RESULTS: Determining the appropriate
      approach to allow for accurate, precise and reproducible drug concentration
      measurements from tissue samples requires addressing issues not present in
      routinely analyzed biological matrices, that is, plasma. We present here the
      issues encountered and techniques applied during the development, validation and
      application of a method for the determination of zotarolimus in a variety of
      tissues. CONCLUSION: When well controlled, analysis of tissue samples can be
      performed in a manner similar to liquid biological matrices.

PMID- 23534426
TI  - Automated liquid microjunction surface sampling-HPLC-MS/MS analysis of drugs and
      metabolites in whole-body thin tissue sections.
AB  - BACKGROUND: The aim of this work was to develop a fully automated liquid
      extraction-based surface sampling system utilizing a commercially available
      autosampler coupled with HPLC-MS/MS detection. RESULTS: Discrete spots selected
      for droplet-based sampling and automated sample queue generation, for both the
      autosampler and MS, were enabled by using in-house developed software. In
      addition, co-registration of spatially resolved sampling positions and HPLC-MS
      information to generate heat maps of compounds monitored for subsequent data
      analysis was also available in the software. The system was evaluated with whole
      body thin tissue sections from propranolol-dosed rats. CONCLUSION: The spatial
      distributions of both the drug and its hydroxypropranolol glucuronide metabolites
      were consistent with previous studies employing other liquid extraction-based
      surface sampling methodologies.

PMID- 23534427
TI  - Simultaneous estimation of amlodipine and atenolol in human plasma: a sensitive
      LC-MS/MS method validation and its application to a clinical PK study.
AB  - BACKGROUND: A highly sensitive, specific and rapid LC-ESI-MS/MS method has been
      developed and validated for simultaneous quantification of amlodipine (AMD) and
      atenolol (ATL) in human plasma (200 ul) using AMD-d4 and ATL-d7, respectively, as
      an internal standard (IS) as per the regulatory guidelines. RESULTS: The SPE
      method was used to extract the analytes and IS from human plasma. The
      chromatographic resolution of AMD, ATL and corresponding IS was achieved using an
      isocratic flow on a C18 column. The total chromatographic run time was 3 min. A
      linear response function was established for the range of concentrations 50-8000
      pg/ml and 10-800 ng/ml for AMD and ATL, respectively, in human plasma.
      CONCLUSION: The intra- and inter-day accuracy and precision values for AMD and
      ATL met the acceptance as per regulatory guidelines. The validated assay was
      applied to a fixed-dose combination of AMD and ATL (Adopin-AT((r))) PK study in
      humans.

PMID- 23534428
TI  - Quantification of the sixth DNA base 5-hydroxymethylcytosine in colorectal cancer
      tissue and C-26 cell line.
AB  - BACKGROUND: DNA methylation at the five position of cytosine is well recognized
      as an important epigenetic modification in human health and disease. Recent
      evidences demonstrated that 5-methylcytosine (5-mC) by the TET family of enzymes
      can be converted to 5-hydroxymethylcytosine (5-hmC). Here, we use an
      ultrasensitive and accurate isotope-based LC-MS/MS method to precisely determine
      the levels of 5-hmC and 5-mC in colorectal cancer and the C-26 colon
      adenocarcinoma cell line. RESULTS: Our data showed that 5-hmC content is
      significantly reduced (approximately sixfold) in colorectal cancer as compared
      with adjacent normal tissue. Similarly, the ratio of 5-hmC to 5-mC dropped from
      0.054 +/- 0.005 in normal tissues, to 0.011 +/- 0.002 in cancer. CONCLUSION: The
      analysis of 5-hmC levels and the ratio of 5-hmC:5-mC during tumor progression
      might provide insight into the role of this modification in cellular
      immortalization and transformation.

PMID- 23534429
TI  - Molecularly imprinted SPE combined with dispersive liquid-liquid microextraction
      for selective analysis of telmisartan in biological and formulation samples.
AB  - BACKGROUND: The present communication describes the combination of molecularly
      imprinted SPE and dispersive liquid-liquid microextraction for the selective
      preconcentration and determination of telmisartan (TEL) in rat urine, plasma and
      pharmaceutical formulation by HPLC. RESULTS: Various factors that can affect the
      extraction efficiency of molecularly imprinted SPE and dispersive liquid-liquid
      microextraction were optimized. The LOD and LOQ were found to be 0.19 and 0.63 ug
      ml(-1) in urine, while in plasma it was found to be 0.28 and 0.87 ug ml(-1),
      respectively. The percentage recovery of TEL in different matrices was found to
      be in the range of 81-97%. CONCLUSION: The proposed method may find wide
      applications in clinical, toxicological and QC laboratories for the routine
      analysis of TEL.

PMID- 23534431
TI  - Reduced amyloid-beta degradation in early Alzheimer's disease but not in the
      APPswePS1dE9 and 3xTg-AD mouse models.
AB  - Alzheimer's disease (AD) is hallmarked by amyloid-beta (Abeta) peptides
      accumulation and aggregation in extracellular plaques, preceded by intracellular
      accumulation. We examined whether intracellular Abeta can be cleared by cytosolic
      peptidases and whether this capacity is affected during progression of sporadic
      AD (sAD) in humans and in the commonly used APPswePS1dE9 and 3xTg-AD mouse
      models. A quenched Abeta peptide that becomes fluorescent upon degradation was
      used to screen for Abeta-degrading cytoplasmic peptidases cleaving the
      aggregation-prone KLVFF region of the peptide. In addition, this quenched peptide
      was used to analyze Abeta-degrading capacity in the hippocampus of sAD patients
      with different Braak stages as well as APPswePS1dE9 and 3xTg-AD mice. Insulin
      degrading enzyme (IDE) was found to be the main peptidase that degrades
      cytoplasmic, monomeric Abeta. Oligomerization of Abeta prevents its clearance by
      IDE. Intriguingly, the Abeta-degrading capacity decreases already during the
      earliest Braak stages of sAD, and this decline correlates with IDE protein
      levels, but not with mRNA levels. This suggests that decreased IDE levels could
      contribute to early sAD. In contrast to the human data, the commonly used
      APPswePS1dE9 and 3xTg-AD mouse models do not show altered Abeta degradation and
      IDE levels with AD progression, raising doubts whether mouse models that
      overproduce Abeta peptides are representative for human sAD.

PMID- 23534432
TI  - Boundary of the nucleotide-binding domain of Streptococcus ComA based on
      functional and structural analysis.
AB  - The ATP-binding cassette (ABC) transporter ComA is a key molecule essential for
      the first step of the quorum-sensing system of Streptococcus. The nucleotide
      binding domains (NBD) of Streptococcus mutans ComA with different N termini, NBD1
      (amino acid residues 495-760), NBD2 (517-760), and NBD3 (528-760), were
      expressed, purified, and characterized. The shortest NBD3 corresponds to the
      region commonly defined as NBD in the database searches of ABC transporters. A
      kinetic analysis showed that the extra N-terminal region conferred a
      significantly higher ATP hydrolytic activity on the NBD at a neutral pH. Gel
      filtration, X-ray crystallography, and mutational analyses suggest that at least
      four to five residues beyond the N-terminal boundary of NBD3 indeed participate
      in stabilizing the protein scaffold of the domain structure, thereby facilitating
      the ATP-dependent dimerization of NBD which is a prerequisite to the catalysis.
      These findings, together with the presence of a highly conserved glycine residue
      in this region, support the redefinition of the N-terminal boundary of the NBD of
      these types of ABC exporters.

PMID- 23534433
TI  - Pre-operative anaemia in colon cancer patients became normal after more than a
      year post-operatively but did not influence oncological outcome in the final
      analysis.
AB  - BACKGROUND: Pre-operative anaemia has been related to adverse outcomes after
      surgical management of colorectal cancer. How various factors may contribute to
      anaemia and also its post-operative recovery has not been extensively
      investigated. METHODS: Two hundred and thirty five colon cancer patients treated
      surgically in a community teaching hospital in Norway between 2007 and 2009 were
      prospectively examined. RESULTS: Anaemia was detected in 53.8%, which was
      dependent on tumour location, albumin level and female gender. More than 60% of
      all patients were overweight or obese. Pre-operative BMI was negatively
      associated with age and positively associated with albumin level (p = 0.018 for
      both). Haemoglobin levels slowly returned to normal during the first year in
      significant incremental steps, coincidental with an increase in BMI. At 6 months
      post-operative, age, albumin, female gender and TNM stage (p = 0.010; p = 0.020;
      p < 0.001; p = 0.028, respectively) were significantly connected with anaemia,
      whereas only age and albumin (p = 0.016; p = 0.004, respectively) were associated
      with a reduced BMI. Pre-operative anaemia gave a significantly worse overall
      survival (p = 0.040) in the univariate analysis but was not significant in the
      multivariate analysis. CONCLUSION: Beside the influence of tumour location, it
      appeared that pre-operative Hgb had some relation to a reduced nutritional state.
      The post-operative recovery of anaemia was more closely related to an improved
      nutritional state. The relation between anaemia and oncological outcome should
      undergo further studies.

PMID- 23534434
TI  - Attitudes of women with breast cancer regarding the doctor-patient relationship.
AB  - Breast cancer is the most common type of cancer among women. The current study
      uses the qualitative method to examine breast cancer patients' viewpoint
      regarding the doctor-patient communication and its implications during their
      treatment. All the women brought up the same central themes: Assuming an active
      attitude in their life. One of the ways to be active is by helping others in her
      situation. Dealing with uncertainty. Need for support from the surroundings.
      Feeling vulnerable in every area of life. The doctor should encourage the patient
      to adopt an active position, try to minimise their uncertainty, support relatives
      to become involved and address all problems and not just the medical complaint of
      their patient. This study is a basis for developing training programmes in the
      medical professions, in order to improve their communication with cancer
      patients.

PMID- 23534435
TI  - Improved performance of organic light-emitting diodes fabricated on Al-doped ZnO
      anodes incorporating a homogeneous Al-doped ZnO buffer layer grown by atomic
      layer deposition.
AB  - In this work, we investigated the use of a homogeneous Al-doped zinc oxide (AZO)
      buffer layer to improve the performance of an organic light-emitting diode (OLED)
      device fabricated on an AZO anode. For this, 10-nm-thick AZO buffer layers with
      Al doping concentrations of 3.1, 4.1, and 5.1 at % were grown on 140-nm-thick AZO
      anode films containing 2.1 at % Al by atomic layer deposition. The electrical
      resistivity of the AZO anode with a homogeneous AZO buffer layer decreased with
      an increase in Al doping concentration up to 4.1 at %; however, the resistivity
      increased at higher doping concentrations in the AZO buffer layer. On the other
      hand, the work functions of the AZO anode with the AZO buffer layer containing
      various Al doping concentrations gradually increased with an increase in Al
      doping concentration from 3.1 to 5.1 at %. Therefore, the best film properties
      were obtained for an AZO anode with an AZO buffer layer containing 4.1 at % Al,
      and the work function value for this film was 4.64 eV. The highest luminance and
      current efficiency values were optimized to be 20290 cd/m(2) and 13.4 cd/A,
      respectively, with the OLED device composed of a DNTPD/TAPC/Bebq2:10% doped RP
      411/Bphen/LiF/Al structure on an AZO anode with an AZO buffer layer containing
      4.1 at % Al.

PMID- 23534436
TI  - Prevalence and correlates of physical, psychological, and sexual intimate partner
      violence in Bolivia.
AB  - Despite increasing awareness that domestic violence is a major public health
      problem, existing studies focus on physical and sexual violence and give little
      attention to psychological violence. This study uses data from the 2008 Bolivia
      Demographic and Health Surveys (BDHS) to examine the prevalence and correlates of
      physical, sexual, and psychological intimate partner violence in Bolivia. The
      results show that psychological intimate partner violence is extremely common
      (affecting nearly one in two women) and often occurs in addition to physical
      violence. While physical, psychological and sexual intimate partner violence have
      several common predictors, there are factors that only affect some types of
      violence. Common risk factors include urban residence, respondent's employment
      status and having witnessed interparental violence in childhood. Although marital
      status is not a risk factor for physical violence, unmarried cohabitation is a
      strong risk factor for psychological intimate partner violence. Our findings
      highlight the need for research to assess the potential consequences of
      psychological intimate partner violence, particularly for women's mental health. 

PMID- 23534437
TI  - Stenting of the right ventricular outflow tract in symptomatic neonatal tetralogy
      of Fallot.
AB  - There is ongoing debate regarding the initial management of symptomatic neonates
      with tetralogy of Fallot. Although neonatal repair can be performed with low
      mortality, it is associated with increased morbidity and long-term impact on
      right ventricular performance. Traditionally, the modified Blalock-Taussig shunt
      remains the palliative procedure of choice. Differential pulmonary artery flow
      may occur and subsequently result in underdevelopment and distortion of pulmonary
      vessels. Transcatheter therapy was previously limited to balloon valvulotomy when
      the obstruction is predominantly at the pulmonary valve level. Stenting of the
      right ventricular outflow tract can enable adequate forward flow; however,
      pulmonary regurgitation may impact on right ventricular performance and cardiac
      output. Stenting of the right ventricular outflow tract with valve sparing
      placement of the stent thus treating the underlying pathophysiology of the
      hypercyanotic spells provides a safe and effective management strategy, improving
      arterial oxygen saturation, avoiding pulmonary regurgitation and encouraging
      pulmonary artery growth. 

PMID- 23534438
TI  - Donor-derived metastatic melanoma in a liver transplant recipient established by
      DNA fingerprinting.
AB  - Metastatic melanoma is a donor-derived malignancy that has rarely been reported
      in liver allograft recipients. We present a case of a transmitted donor-derived
      melanoma to a liver allograft recipient in whom the diagnosis was established by
      polymerase chain reaction-based DNA fingerprinting. A 52-year-old African
      American man underwent a successful orthotropic liver transplant for alcohol
      induced cirrhosis. One year after the orthotropic liver transplant, he presented
      at our institution with diffuse abdominal pain, and a computed tomography scan of
      the abdomen and chest showed innumerable masses diffusely involving the liver and
      multiple subcutaneous nodules in the abdominal and chest wall. A liver biopsy
      confirmed the diagnosis of metastatic melanoma. The origin of melanoma was traced
      to the donor by DNA fingerprinting of the native liver, the donor liver, and the
      donor gallbladder. Chemotherapy was initiated with temozolomide (75 mg/m2 daily)
      and thalidomide (50 mg daily), to which he responded within 8 weeks with
      radiologic improvement in metastatic lesions. Tacrolimus was switched to
      sirolimus because of renal insufficiency as well as reported effectiveness
      against melanoma. Our patient survived for 9 months after the diagnosis of
      metastatic melanoma. He ultimately died of brain metastases. Donor-derived
      metastatic melanoma is a rare cancer with the highest transmission and mortality
      rates, which requires better recognition. Prompt diagnosis of donor-derived
      melanoma is critical and can be achieved reliably with polymerase chain reaction
      based DNA analysis. Management options after diagnosis include de-escalation of
      immunosuppression, with or without urgent organ removal or retransplant. The
      roles of chemotherapy, immunotherapy, and radiotherapy require further study. 

PMID- 23534439
TI  - Binary recombination of H3(+) and D3(+) ions with electrons in plasma at 50-230
      K.
AB  - The results of an experimental study of the H3(+) and D3(+) ions recombination
      with electrons in afterglow plasmas in the temperature range 50-230 K are
      presented. A flowing afterglow apparatus equipped with a Langmuir probe was used
      to measure the evolution of the electron number density in the decaying plasma.
      The obtained values of the binary recombination rate coefficient are
      alphabinH3(+) = (6.0 +/- 1.8) * 10(-8)(300/T)(0.36+/-0.09) cm(3) s(-1) for H3(+)
      ions in the temperature range 80-300 K and alphabinD3(+) = (3.5 +/- 1.1) * 10(
      8)(300/T)(0.73+/-0.09) cm(3) s(-1) for D3(+) ions in the temperature range 50-300
      K. This is the first measurement of the binary recombination rate coefficient of
      H3(+) and D3(+) ions in a plasma experiment down to 50 K. 

PMID- 23534440
TI  - Bioinformatics and molecular dynamics simulation study of L1 stalk non-canonical
      rRNA elements: kink-turns, loops, and tetraloops.
AB  - The L1 stalk is a prominent mobile element of the large ribosomal subunit. We
      explore the structure and dynamics of its non-canonical rRNA elements, which
      include two kink-turns, an internal loop, and a tetraloop. We use bioinformatics
      to identify the L1 stalk RNA conservation patterns and carry out over 11.5 MUs of
      MD simulations for a set of systems ranging from isolated RNA building blocks up
      to complexes of L1 stalk rRNA with the L1 protein and tRNA fragment. We show that
      the L1 stalk tetraloop has an unusual GNNA or UNNG conservation pattern deviating
      from major GNRA and YNMG RNA tetraloop families. We suggest that this deviation
      is related to a highly conserved tertiary contact within the L1 stalk. The
      available X-ray structures contain only UCCG tetraloops which in addition differ
      in orientation (anti vs syn) of the guanine. Our analysis suggests that the anti
      orientation might be a mis-refinement, although even the anti interaction would
      be compatible with the sequence pattern and observed tertiary interaction.
      Alternatively, the anti conformation may be a real substate whose population
      could be pH-dependent, since the guanine syn orientation requires protonation of
      cytosine in the tertiary contact. In absence of structural data, we use molecular
      modeling to explore the GCCA tetraloop that is dominant in bacteria and suggest
      that the GCCA tetraloop is structurally similar to the YNMG tetraloop. Kink-turn
      Kt-77 is unusual due to its 11-nucleotide bulge. The simulations indicate that
      the long bulge is a stalk-specific eight-nucleotide insertion into consensual
      kink-turn only subtly modifying its structural dynamics. We discuss a possible
      evolutionary role of helix H78 and a mechanism of L1 stalk interaction with tRNA.
      We also assess the simulation methodology. The simulations provide a good
      description of the studied systems with the latest bsc0chiOL3 force field showing
      improved performance. Still, even bsc0chiOL3 is unable to fully stabilize an
      essential sugar-edge H-bond between the bulge and non-canonical stem of the kink
      turn. Inclusion of Mg(2+) ions may deteriorate the simulations. On the other
      hand, monovalent ions can in simulations readily occupy experimental Mg(2+)
      binding sites.

PMID- 23534441
TI  - Expression and function of the Transforming Growth Factor-b system in the human
      and rat enteric nervous system.
AB  - BACKGROUND: Transforming growth factor-betas (TGF-bs) are pleiotropic growth
      factors exerting neurotrophic functions upon various neuronal populations of the
      central nervous system. In contrast, the role of TGF-b isoforms in the enteric
      nervous system (ENS) is largely unknown. We therefore analyzed the gene
      expression pattern of the TGF-b system in the human colon and in rat myenteric
      plexus, and smooth muscle cell cultures and determined the effect of TGF-b
      isoforms on neuronal differentiation. METHODS: Human colonic samples as well as
      cultured rat myenteric plexus, and smooth muscle cells were assessed for mRNA
      expression levels of the TGF-b system (TGF-b1-3, TbR-1-3) by qPCR. The colonic
      wall was separated into mucosa and tunica muscularis and enteric ganglia were
      isolated by laser microdissection (LMD) to allow site-specific gene expression
      analysis. Effects of TGF-b isoforms on neurite outgrowth and branching pattern of
      cultured myenteric neurons were monitored. KEY RESULTS: mRNA expression of the
      TGF-b system was detected in all compartments of the human colonic wall as well
      as in LMD-isolated myenteric ganglia. Cultured myenteric neurons and smooth
      muscle cells of rat intestine also showed mRNA expression of all ligands and
      receptors. Transforming growth factor-b2 treatment increased neurite length and
      branching pattern in cultured myenteric neurons. CONCLUSIONS & INFERENCES: The
      TGF-b system is abundantly expressed in the human and rat ENS arguing for an auto
      /paracrine function of this system on enteric neurons. Transforming growth factor
      b2 promotes neuronal differentiation and plasticity characterizing this molecule
      as a relevant neurotrophic factor for the ENS.

PMID- 23534443
TI  - Ambient aerodynamic desorption/ionization method for microparticle mass
      measurement.
AB  - An ambient desorption/ionization method, named aerodynamic desorption (AD), was
      proposed for the in situ rapid mass measurement of microparticles. The AD method
      exploited the discontinuous atmospheric pressure interface (DAPI) to generate a
      pulsed airflow, which was used to desorb the microparticles under atmospheric
      pressure. Various microparticles, e.g., bacteria, cell, polystyrene, synthetic
      diamond, and silica particles, with different size and surface component were
      successfully desorbed. Similar to that in the conventional laser-induced acoustic
      desorption (LIAD) method, these microparticles were desorbed as precharged ions
      in the AD process and the charge number was largely relevant to the particle
      size. However, compared with LIAD, the sensitivity of the AD method was higher. A
      lower concentration of particles was required for the analysis. In addition, the
      construction and sampling process of AD source were much simpler. All types of
      liquid, solid, or/and gaseous samples can be directly sampled under ambient
      condition. As a demonstration of this AD method, the in situ mass analysis of red
      blood cells (RBCs) and E. coli bacteria were carried out using a homemade ambient
      AD mass spectrometer consisting of AD source, QIT mass analyzer, and charge
      detector. Their mass and mass distributions were obtained successfully. 

PMID- 23534442
TI  - Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers
      and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors.
AB  - A series of 3-substituted 1,5-diarylpyrroles bearing a nitrooxyalkyl side chain
      linked to different spacers were designed. New classes of pyrrole-derived
      nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective
      inhibitors and NO donors were synthesized and are herein reported. By taking into
      account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into
      corresponding alcohols, derivatives 17 and 18 were also studied. Nitrooxy
      derivatives showed NO-dependent vasorelaxing properties, while most of the
      compounds proved to be very potent and selective COX-2 inhibitors in in vitro
      experimental models. Further in vivo studies on compounds 9a,c and 17a
      highlighted good anti-inflammatory and antinociceptive activities. Compound 9c
      was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1beta
      (IL-1beta), showing cartilage protective properties. Finally, molecular modeling
      and (1)H- and (13)C-NMR studies performed on compounds 6c,d, 9c, and 10b allowed
      the right conformation of nitrooxyalkyl ester and ether side chain of these
      molecules within the COX-2 active site to be assessed.

PMID- 23534444
TI  - Calculation of electron transfer rates using mixed quantum classical approaches:
      nonadiabatic limit and beyond.
AB  - We investigate the applicability of the Ehrenfest and surface hopping methods to
      calculate electron transfer rates using the spin-boson model with different
      parameters. Rate constants are obtained from short time dynamics performed in
      both the diabatic and adiabatic basis sets. Numerical results and theoretical
      analysis show that these two methods can be reasonably accurate in the
      nonadiabatic limit, by staying close to an approximate Fermi's golden rule.
      Beyond the nonadiabatic limit, the calculated mixed quantum classical rates are
      compared with numerical exact results, and similar accuracy was found as in the
      nonadiabatic limit. The relation between the current finding and recent studies
      using the surface hopping method based on long time dynamics is also discussed.
      It is found that the short time dynamics could be more accurate in calculating
      rate constants using the mixed quantum classical methods. 

PMID- 23534445
TI  - Consumption of unpasteurized milk and its effects on atopy and asthma in children
      and adult inhabitants in rural Poland.
AB  - BACKGROUND: Consumption of unpasteurized cow's milk has been identified as a
      possible protective factor for atopy and asthma. Most studies have been conducted
      among children and in farming populations. We investigated the effects of
      consumption of unpasteurized milk in early life on atopy, asthma, and rhinitis in
      village and town inhabitants in a region of Poland and assessed whether any
      protective effects of milk consumption differed according to place of residence
      and farming status. METHODS: We surveyed the inhabitants (aged >5 years) of a
      small town and seven nearby villages in southwest Poland (n = 1700, response rate
      88%). Participants (or their parents for those <16 years of age) completed a
      questionnaire on farm exposures and symptoms of asthma and rhinitis. In
      particular, information was collected on unpasteurized milk consumption in early
      life. Atopy was assessed using skin prick tests. RESULTS: Consumption of
      unpasteurized milk in the first year of life was inversely associated with atopy
      and asthma both among town and village inhabitants - town: adjusted odds ratio
      (aOR) for atopy 0.46 [95% confidence interval (CI) 0.37-0.52] asthma 0.51 (0.32
      0.74); villages: atopy 0.59 (0.44-0.70) and asthma 0.59 (0.42-0.74). For atopy,
      the protective effect was more clearly seen among nonfarmers (0.42; 0.34-0.46)
      than in farmers (0.82; 0.54-1.11). For doctor-diagnosed hay fever and current
      rhinitis symptoms, the protective effect was only observed among town inhabitants
      and/or nonfarmers. CONCLUSIONS: Early-life exposure to unpasteurized milk may
      protect against atopy, asthma, and related conditions, independently of place of
      residence and farming status, and in both children and adults.

PMID- 23534446
TI  - Taking shape: supporting preschoolers' acquisition of geometric knowledge through
      guided play.
AB  - Shape knowledge, a key aspect of school readiness, is part of early mathematical
      learning. Variations in how children are exposed to shapes may affect the pace of
      their learning and the nature of their shape knowledge. Building on evidence
      suggesting that child-centered, playful learning programs facilitate learning
      more than other methods, 4- to 5-year-old children (N = 70) were taught the
      properties of four geometric shapes using guided play, free play, or didactic
      instruction. Results revealed that children taught shapes in the guided play
      condition showed improved shape knowledge compared to the other groups, an effect
      that was still evident after 1 week. Findings suggest that scaffolding techniques
      that heighten engagement, direct exploration, and facilitate "sense-making," such
      as guided play, undergird shape learning.

PMID- 23534448
TI  - Synthesis of complex polymeric telluridoindates from KInTe2.
AB  - Four new polymeric telluridoindates [K(18-crown-6)][InTe2].2en (1) (18-crown-6 =
      1,4,7,10,13,16-hexaoxacyclooctadecane), [K([2.2.2]crypt)]2[In2Te6].0.5en (2)
      ([2.2.2]crypt = 4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane),
      [HTMDP]2[In4Te8] (3) (TMDP = 4,4'-trimethylenedipiperidine), and
      [HDAP]8[In12Te23] (4) (DAP = 1,3-diaminopropane) were prepared from KInTe2 as a
      starting material. With [InTe4] tetrahedra as the primary building unit in all
      four compounds, there is a significant increase in complexity in going from the
      simple chain-like anionic structures in 1 and 2 to an intricate band-type anion
      in 3 and finally an anionic framework with lig-topology in 4.

PMID- 23534447
TI  - Emerging role of long acting muscarinic antagonists for asthma.
AB  - Acetlycholine is involved in the control of airway smooth muscle constriction and
      in recruitment of inflammatory cells via neuronal and paracrine effects on
      muscarinic type 3 receptors. Long acting muscarinic antagonists (LAMA) are well
      established in guidelines for COPD but are not currently licensed for use in
      asthma. There are emerging data from key clinical trials to show that LAMA may
      confer bronchodilator effects and improved control when used in addition to
      inhaled corticosteroid (ICS) alone or in conjunction with long acting beta
      adrenoceptor agonists (LABA). Further studies in persistent asthmatic patients
      are required to evaluate ICS sparing effects of LAMA looking particularly at
      airway hyper-responsiveness and surrogate inflammatory markers, in addition to
      evaluation of possible synergy between LAMA and LABA when given together. Future
      possible development of combination inhalers comprising ICS/LAMA or ICS/LAMA/LABA
      will require long term studies looking at asthma control and exacerbations in
      both adult and paediatric patients. 

PMID- 23534449
TI  - Enhanced antitumor response mediated by the codelivery of paclitaxel and
      adenoviral vector expressing IL-12.
AB  - It has been well-established that chemo-immunotherapy using cytotoxic drugs and
      appropriate cytokines offers a promising approach for the treatment of neoplastic
      diseases. In view of this, to improve melanoma treatment effect, our study
      developed a new codelivery system (AL/Ad5/PTX) that paclitaxel (PTX) and
      adenovirus encoding for murine interleukin-12 (Ad5-mIL-12) were incorporated into
      anionic liposomes (AL). First, AL/Ad5/PTX complexes were prepared by
      incorporating Ad5 into anionic PTX liposomes using calcium-induced phase change.
      Second, the size distribution and zeta potential of AL/Ad5/PTX were investigated.
      Third, the results of in vitro transduction assays showed that PTX introduced
      into AL/Ad-luc or AL/Ad5-mIL-12 highly enhanced gene transduction efficiency in
      B16 cells than naked Ad5 or AL/Ad complexes while it had no comparability in A549
      cells. Finally, a melanoma-bearing mouse model was established to assess the
      antitumor effect. Tumor growth inhibition and prolonged survival time,
      accompanied by increased mIL-12 or interferon-gamma (IFN-gamma) expression levels
      in serum or tumor sites, were observed in mice treated with AL/Ad5-mIL-12/PTX, as
      compared with those treated with either AL/Ad5-mIL-12 or AL/PTX. In conclusion,
      these results suggested that codelivery of Ad5-mIL-12 and PTX incorporated into
      AL could be a relatively efficient strategy for the treatment of melanoma.

PMID- 23534450
TI  - Antimicrobial effect of sour pomegranate sauce on Escherichia coli O157:H7 and
      Staphylococcus aureus.
AB  - Pomegranate sauce is one of the most popular pomegranate products produced in
      Turkey. This study was conducted to determine the minimum inhibitory
      concentrations (MICs) of both traditional and commercial sour pomegranate sauce
      samples on Staphylococcus aureus (ATCC 25923) and Escherichia coli O157:H7 (ATCC
      43895). The initial microflora of the pomegranate sauce samples was determined by
      performing the enumerations of total aerobic mesophilic bacteria, yeast and mold,
      S. aureus, E. coli, and the determination of Salmonella spp. MIC tests were
      applied to the neutralized and the original (unneutralized) sour pomegranate
      sauce samples in order to put forth the inhibition effect depending on low pH
      value. It was found that inhibitory effect of the traditional and the commercial
      samples, except one sample, on pathogens was not only due to the acidity of the
      products. The results of MIC tests indicated that although both traditional and
      commercial samples showed a considerable inhibitory effect on test
      microorganisms, the traditional pomegranate sauce samples were more effective
      than the commercial ones.

PMID- 23534451
TI  - Early interventions for diabetes and dysglycaemia. Surgery in the treatment of
      obesity and diabetes. Abstracts of the 5th International Congress on Prediabetes
      and the Metabolic Syndrome. Vienna, Austria. April 18-20, 2013.

PMID- 23534453
TI  - The role of leukotriene B4 in early stages of experimental paracoccidioidomycosis
      induced in phenotypically selected mouse strains.
AB  - Paracoccidioidomycosis is a human systemic mycosis caused by the fungus
      Paracoccidioides brasiliensis. The mechanisms involved in innate immune response
      to this fungus are not fully elucidated. Leukotrienes are known to be critical
      for the clearance of various microorganisms, mainly by mediating the microbicidal
      function of phagocytes. We investigated the involvement of leukotriene B4 in the
      early stages of experimental paracoccidioidomycosis, which was induced by
      intratracheal inoculation of the fungus in selected mouse lines. The mouse lines
      utilized were produced through bi-directional phenotypic selection, endowed with
      maximal or minimal acute inflammatory reactivity, and designated AIRmax and
      AIRmin, respectively. AIRmax mice were more resistant to the infection, which was
      demonstrated by reduced lung fungal loads. However, the two lines produced
      similar amounts of leukotriene B4, and pharmacological inhibition of this
      mediator provoked similar fungal load increases in the two lines. The lower
      fungal load in the AIRmax mice was associated with a more effective inflammatory
      response, which was characterized by enhanced recruitment and activation of
      phagocytic cells and an increased production of activator cytokines. This process
      resulted in an increased release of fungicidal molecules and a diminution of
      fungal load. In both lines, leukotriene production was associated with a
      protective response in the lung that was consequent to the effect of this
      eicosanoid on the influx and activation of phagocytes.

PMID- 23534454
TI  - A 26-week repeated-dose toxicity study of allisartan isoproxil in Sprague-Dawley
      rats.
AB  - Allisartan isoproxil (ALS-3) is a selective, nonpeptide blocker of the
      angiotensin II type 1 receptor. It is a new antihypertensive drug under
      development with a novel chemical structure. The aim of this study was to
      evaluate the potential toxicity of ALS-3 in Sprague-Dawley rats. Animals were
      orally administered either vehicle or ALS-3 at doses of 20, 80 and 320 mg/kg once
      daily for 26 weeks, followed by a 6-week recovery period. Toxicity was assessed
      by mortality, clinical signs, body weight, food consumption, hematology,
      coagulation, serum chemistry, gross necropsy, organ weights and microscopic
      examination. Decreased body-weight gain was noted at 320 mg/kg/day in both sexes
      as well as at the 80-mg/kg/day dose in females. Food consumption was decreased at
      all doses in males and at 80- and 320-mg/kg/day doses in females. Decreased
      erythrocyte parameters (erythrocyte count, hemoglobin and hematocrit) were
      observed in males receiving 320 mg/kg/day. Elevated urea nitrogen (BUN),
      increased kidney weight, decreased heart weight and exacerbation of chronic
      progressive nephropathy (CPN) severity were all observed in males at 80 and 320
      mg/kg/day. However, only an exacerbated incidence of CPN was observed in females
      at 320 mg/kg/day. All changes were reversed after the 6-week recovery period,
      except BUN and CPN. Based on these results, we concluded that a dose of 20
      mg/kg/day was the no observed adverse effect level. The toxicity target organ was
      the kidney. Males were more affected than females.

PMID- 23534455
TI  - Realist review to understand the efficacy of culturally appropriate diabetes
      education programmes.
AB  - AIMS: Minority populations often face linguistic, cultural and financial barriers
      to diabetes education and care. The aim was to understand why culturally
      appropriate diabetes education interventions work, when they work best and for
      whom they are most effective. METHODS: This review used a critical realist
      approach to examine culturally appropriate diabetes interventions. Beginning with
      the behavioural model and access to medical care, it reanalysed 11 randomized
      controlled trials from a Cochrane systematic review and related programme and
      training documents on culturally appropriate diabetes interventions. The analysis
      examined context and mechanism to understand their relationship to participant
      retention and statistically improved outcomes. RESULTS: Minority patients with
      language barriers and limited access to diabetes programmes responded to
      interventions using health workers from the same ethnic group and interventions
      promoting culturally acceptable and financially affordable food choices using
      local ingredients. Programme incentives improved retention in the programmes and
      this was associated with improved HbA(1c) levels at least in the short term.
      Adopting a positive learning environment, a flexible and less intensive approach,
      one-to-one teaching in informal settings compared with a group approach in
      clinics led to improved retention rates. CONCLUSIONS: Minority and uninsured
      migrants with unmet health needs showed the highest participation and HbA(1c)
      responses from culturally appropriate programmes.

PMID- 23534456
TI  - Glycaemic index, carbohydrate substitution for fat and risk of CHD in men.
AB  - We have examined the associations between dietary glycaemic index (GI),
      substitutions of total, low-, medium- and high-GI carbohydrates for fat and the
      risk of CHD. The study consisted of 21 955 male smokers, aged 50-69 years, within
      the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The diet was
      assessed at baseline using a validated FFQ. During a 19-year follow-up, 4379 CHD
      cases (2377 non-fatal myocardial infarctions and 2002 CHD deaths) were identified
      from national registers. Relative risks (RR) and CI for CHD were analysed using
      Cox proportional hazards modelling, and multivariate nutrient density models were
      applied to examine the associations between the substitutions of macronutrients
      and the risk of CHD. Dietary GI was inversely associated with CHD risk:
      multivariate RR in the highest v. lowest quintile was 0.89 (95 % CI 0.81, 0.99).
      Replacement of higher-GI carbohydrates with lower-GI carbohydrates did not
      associate with the risk. Replacing saturated and trans-fatty acids with
      carbohydrates was associated with decreased CHD risk: RR for substitution of 2 %
      of energy intake was 0.97 (95 % CI 0.94, 0.99). On the contrary, replacing MUFA
      with carbohydrates was associated with an increased risk: RR for substitution of
      2 % of energy intake was 1.08 (95 % CI 1.01, 1.16). We conclude that in the
      present study population, contrary to the hypothesis, a lower GI does not
      associate with a decreased risk of CHD. The associations of carbohydrates with
      CHD risk depend on the fatty acid composition of the diet.

PMID- 23534457
TI  - Nonamethylcyclopentyl cation rearrangement mysteries solved.
AB  - The C1 nonamethylcyclopentyl cation minimum undergoes complete methyl scrambling
      in SbF5 with a 7 kcal/mol barrier. This corresponds to the rate-limiting
      conformational interconversion of enantiomeric hyperconjomers via a C(s)
      transition structure (above right). A remarkable, more rapid, second process only
      exchanges methyls within sets of four and five (blue and red, see above), as has
      been observed experimentally at low temperatures. The computed ~2 kcal/mol
      barrier involves a C(s) [1s,2s] sigmatropic methyl shift transition structure
      (above left).

PMID- 23534458
TI  - Aliskiren reduces morning blood pressure in hypertensive patients with diabetic
      nephropathy on hemodialysis.
AB  - Our previous study indicated that the exchange from an angiotensin receptor
      blocker (ARB) to aliskiren reduced morning blood pressure and albuminuria in
      hypertensive patients with diabetic nephropathy. We extended the above study and
      assessed the effects of exchanging from an ARB to aliskiren on home blood
      pressure in hypertensive patients with diabetic nephropathy on chronic
      hemodialysis. The patients who were persistently hypertensive despite
      antihypertensive therapy, including ARB, were considered as candidates for the
      exchange from the ARB to aliskiren. Patients' age and durations of diabetes and
      hemodialysis were averaged as 62 +/- 9 years old, 15 +/- 8 and 7 +/- 3 years,
      respectively. Aliskiren decreased morning systolic blood pressure (149 +/- 14 to
      144 +/- 13 mm Hg, n = 30, P < .01) and plasma renin activity (3.5 +/- 1.1 to 1.2
      +/- 0.6 ng/mL/h, P < .01) without changes in serum potassium. Aliskiren also
      reduced interdialytic weight gain (2.7 +/- 0.6 to 2.5 +/- 0.5 kg/interval, P <
      .05) and attenuated the magnitude of intradialytic declines in systolic (-20 +/-
      11 to -17 +/- 10 mm Hg, P < .05) and diastolic blood pressure (-9 +/- 6 to -5 +/-
      5 mm Hg, P < .01). The exchange from an ARB to aliskiren is safe and useful to
      control home blood pressure in hypertensive hemodialysis patients with diabetic
      nephropathy. Aliskiren reduced both intradialytic blood pressure drops and
      interdialytic weight gain in patients with DN.

PMID- 23534460
TI  - Arg314 is essential for catalysis by N-acetyl neuraminic acid synthase from
      Neisseria meningitidis.
AB  - The sialic acid N-acetylneuraminic acid (NANA) has a key role in the pathogenesis
      of a select number of neuroinvasive bacteria such as Neisseria meningitidis.
      These pathogens coat themselves with polysialic acids, mimicking the exterior
      surface of mammalian cells and consequentially concealing the bacteria from the
      host's immune system. NANA is synthesized in bacteria by the homodimeric enzyme
      NANA synthase (NANAS), which catalyzes a condensation reaction between
      phosphoenolpyruvate (PEP) and N-acetylmannosamine (ManNAc). NANAS is closely
      related to the alpha-keto acid synthases 3-deoxy-d-arabino-heptulosonate 7
      phosphate synthase and 3-deoxy-d-manno-octulosonate 8-phosphate synthase. NANAS
      differs from these enzymes in that it contains an antifreeze protein like (AFPL)
      domain, which extends from the C-terminal of the (beta/alpha)8 barrel containing
      the active site and contributes a highly conserved arginine (Arg314) into the
      active site of the opposing monomer chain. We have investigated the role of
      Arg314 in NmeNANAS through mutagenesis and a combination of kinetic and
      structural analyses. Using isothermal titration calorimetry and molecular
      modeling, we have shown that Arg314 is required for the catalytic function of
      NANAS and that the delocalized positively charged guanidinium functionality of
      this residue provides steering of the sugar substrate ManNAc for suitable
      placement in the active site and thus reaction with PEP.

PMID- 23534459
TI  - Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension.
AB  - Arsenite is one of the most toxic chemical substances known and is assumed to
      exert detrimental effects on viability even at lowest concentrations. By contrast
      and unlike higher concentrations, we here find that exposure to low-dose arsenite
      promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose
      arsenite promotes resistance against thermal and chemical stressors and extends
      lifespan of this metazoan, whereas higher concentrations reduce longevity. While
      arsenite causes a transient increase in reactive oxygen species (ROS) levels in
      C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending
      capabilities of arsenite, indicating that transiently increased ROS levels act as
      transducers of arsenite effects on lifespan, a process known as mitohormesis.
      This requires two transcription factors, namely DAF-16 and SKN-1, which employ
      the metallothionein MTL-2 as well as the mitochondrial transporter TIN-9.1 to
      extend lifespan. Taken together, low-dose arsenite extends lifespan, providing
      evidence for nonlinear dose-response characteristics of toxin-mediated stress
      resistance and longevity in a multicellular organism.

PMID- 23534461
TI  - Iron stores assessment in alcoholic liver disease.
AB  - BACKGROUND: The relation between alcoholic liver disease (ALD) and iron overload
      is well known. Liver biopsy is the gold standard for assessing iron stores. MRI
      is also validated for liver iron concentration (LIC) assessment. We aimed to
      assess the effect of active drinking in liver iron stores and the practicability
      of measuring LIC by MRI in ALD patients. MATERIALS AND METHODS: We measured LIC
      by MRI in 58 ALD patients. We divided patients into two groups - with and without
      active alcoholism - and we compared several variables between them. We evaluated
      MRI-LIC, liver iron stores grade, ferritin and necroinflammatory activity grade
      for significant correlations. RESULTS: Significant necroinflammation (40.0% vs.
      4.3%), LIC (40.1 vs. 24.3 umol/g), and ferritin (1259.7 vs. 568.7 pmol/L) were
      significantly higher in drinkers. LIC values had a strong association with iron
      stores grade (r s = 0.706). Ferritin correlated with LIC (r s = 0.615), iron
      stores grade (r s = 0.546), and necroinflammation (r s = 0.313). The odds ratio
      for elevated serum ferritin when actively drinking was 7.32. CONCLUSION: Active
      alcoholism is associated with increased ALD activity. It is also the key factor
      in iron overload. Scheuers' semiquantitative score with Perls' staining gives a
      fairly accurate picture of liver iron overload. Serum ferritin also shows a good
      correlation with LIC values and biopsy iron stores grade. As most patients
      present only with mild iron overload, serum ferritin measurement and
      semiquantitative evaluation of iron stores are adequate, considering MRI high
      cost. However, if MRI is required to evaluate liver structure, LIC assessment
      could be performed without added cost.

PMID- 23534462
TI  - Assessment of oral care needs of patients treated at the intensive care unit.
AB  - AIMS AND OBJECTIVES: To assess the oral hygiene needs and the status of the oral
      mucus membranes of patients being treated in an intensive care unit and to
      determine the personal- or treatment-related variables associated with oral
      hygiene and the status of the oral mucus membranes of patients. BACKGROUND: Oral
      hygiene has an impact on the clinical outcomes and well-being of critically ill
      patients. DESIGN: A descriptive, cross-sectional design was used. METHOD: The
      study was conducted in the intensive care unit of a private hospital located in
      Istanbul. The study sample consisted of 60 patients treated in the intensive care
      unit for five consecutive days. Oral assessments were conducted once per day
      every morning for five days. The oral assessments were performed using the Oral
      Assessment Tool and Oral Assessment Checklist. RESULTS: The oral hygiene status
      and the health of the oral mucus membranes improved over the consecutive five-day
      assessments, and the routine oral care provided by nurses in the intensive care
      unit was effective in preventing oral mucus membrane-related complications.
      CONCLUSIONS: The frequency of oral care and oral moistening should be determined
      according to the patient's condition and the presence of risk factors for oral
      complications. Oral mucus membranes should be assessed closely and systematically
      in all critically ill patients who are mechanically ventilated, are receiving
      oxygen therapy, are undergoing invasive procedures, have a history of chronic
      health problems or are receiving enteral or parenteral nutrition. RELEVANCE TO
      CLINICAL PRACTICE: To prevent infections or complications during intensive care
      treatment, it is important for nurses working in critical care units to develop
      and implement oral care assessments and evidence-based oral care protocols.

PMID- 23534463
TI  - Potent in vitro interference of fleroxacin in DNA-binding, unwinding and ATPase
      activities of Bloom helicase.
AB  - OBJECTIVE: To study the effect of fleroxacin (FLRX) on biological properties of
      Bloom (BLM) helicase catalytic core (BLM642-1290 helicase) in vitro and the
      molecular mechanism of interaction between the two molecules. METHODS: DNA
      binding and unwinding activities of BLM642-1290 helicase were assayed by
      fluorescence polarization and gel retardation assay under conditions that the
      helicase was subjected to different concentrations of FLRX. Effect of FLRX on
      helicase ATPase activity was analyzed by phosphorus-free assay based on a
      colorimetric estimation of ATP hydrolysis-produced inorganic phosphate. Molecular
      mechanism of interaction between the two molecules was assayed by ultraviolet and
      fluorescence spectra. RESULTS: The DNA unwinding and ATPase activities of BLM642
      1290 helicase were inhibited whereas the DNA-binding activity was promoted in
      vitro. A BLM-FLRX complex was formed through one binding site, electrostatic and
      hydrophobic interaction force. Moreover, the intrinsic fluorescence of the
      helicase was quenched by FLRX as a result of non-radioactive energy transfer. The
      biological activity of helicase was affected by FLRX, which may be through an
      allosteric mechanism and stabilization of enzyme conformation in low helicase
      activity state, disruption of the coupling of ATP hydrolysis to unwinding, and
      blocking helicase translocation on DNA strands. CONCLUSION: FLRX may affect the
      biological activities and conformation of BLM642-1290 helicase, and DNA helicase
      may be used as a promising drug target for some diseases.

PMID- 23534464
TI  - Prevalence and risk assessment of Campylobacter jejuni in chicken in China.
AB  - OBJECTIVE: To understand the occurrence and distribution of Campylobacter jejuni
      in chicken in China, assess its health risk to the Chinese population, and
      provide recommendations for effective risk control. METHODS: Data from the
      National Food Safety Risk Surveillance Network on Campylobacter jejuni between
      2007 and 2010 and from published articles were analyzed. Eleven parameters were
      used based on the whole chicken preparation process and prevalence of
      Campylobacter jejuni for risk assessment by using the Ross-Sumner Method.
      RESULTS: The detection rates of Campylobacter jejuni in raw chicken were between
      0.29% and 2.28% during 2007-2010 in China (more than 20 provinces). The
      probability of illness caused by Campylobacter jejuni due to chicken consumption
      was around six out of one million consumers per day in urban areas and around one
      out of one million consumers per day in rural areas. Total predicted illnesses
      per year was about 736 000, accounting for 1.60/00 of the general population in
      urban areas and about 301 000, accounting for 0.370/00 of the total population in
      rural areas. The risk rankings of Campylobacter jejuni in chicken were 52 and 49
      in urban and rural areas, respectively. CONCLUSION: A high risk score for
      Campylobacter jejuni in chicken was obtained in China. This result may contribute
      to development of food safety management strategies. Key efforts should be made
      to control the risk of Campylobacter jejuni in chicken in China, especially in
      chick breeding and chicken preparation processes.

PMID- 23534465
TI  - Prevention of osteopenia and dyslipidemia in rats after ovariectomy with combined
      aspirin and low-dose diethylstilbestrol.
AB  - OBJECTIVE: To study whether effect of aspirin plus low-dose diethylstilbestrol is
      more effective and safer than high diethylstilbestrol dose alone on prevention of
      ovariectomy-induced osteopenia and dyslipidemia. METHODS: Thirty-eight 4-month
      old female SD rats were divided into baseline (BAS) group (n=6), sham operation
      group (n=8) and ovariectomy (OVX) group (n=24). The OVX group was further divided
      into vehicle treatment group (n=8), diethylstilbestrol (30 MUg/kg*d) treatment
      group (OVX+D30 group, n=8), and aspirin (9 mg/kg*d) plus diethylstilbestrol (10
      MUg/kg*d) treatment group (OVX+A-D10 group, n=8). Their left tibiae were
      collected for the bone histomorphometric analysis in undecalcified sections. Left
      femurs were collected for the bone mineral density measurement. RESULTS: The body
      weight and serum cholesterol were increased, while uterine weight and cancellous
      bone mass were decreased in OVX rats compared with the SHAM group. Cancellous
      bone mass was significantly increased, while body weight and bone resorption
      parameters were decreased in both A-D10 and D30 treatment group compared with OVX
      group. The rats treated with A-D10 showed significantly increased in bone
      formation parameters and decreased in serum triglyceride compared with the D30
      treated rats. CONCLUSION: Aspirin plus low-dose diethylstilbestrol can
      effectively prevent osteopenia by reducing bone resorption, and is thus a better
      treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol
      alone.

PMID- 23534466
TI  - Protective effects of quercetin on cadmium-induced cytotoxicity in primary
      cultures of rat proximal tubular cells.
AB  - OBJECTIVE: To investigate the protective effects of quercetin on cadmium-induced
      cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. METHODS:
      Primary cultures of rPT cells undergoing exponential growth were incubated with
      1.0 MUg/mL quercetin and/or cadmium (2.5, 5.0 MUmol/L), in a serum-free medium at
      37  degrees C at different time intervals. Commercial kits were used and flow
      cytometric analyses were performed on rPT cell cultures to assay apoptosis and
      oxidative stress. RESULTS: Exposure of rPT cells to cadmium acetate (2.5, 5.0
      umol/L) induced a decrease in cell viability, caused an increase in apoptotic
      rate and apoptotic morphological changes. Simultaneously, elevation of
      intracellular reactive oxygen species, malondialdehyde and calcium levels,
      depletion of mitochondrial membrane potential and intracellular glutathione, and
      inhibition of Na+, K+-ATPase, Ca2+-ATPase, glutathione peroxidase (GSH-Px),
      catalase (CAT), and superoxide dismutase (SOD) activities were revealed during
      the cadmium exposure of rPT cells. However, simultaneous supplementation with 1
      ug/mL quercetin protected rPT cells against cadmium-induced cytotoxicity through
      inhibiting apoptosis, attenuating lipid peroxidation, renewing mitochondrial
      function and elevating the intracellular antioxidants (non-enzymatic and enzymic)
      levels. CONCLUSION: The present study has suggested that quercetin, as a widely
      distributed dietary antioxidant, contributes potentially to prevent cadmium
      induced cytotoxicity in rPT cells.

PMID- 23534467
TI  - Involvement of the mitochondrion-dependent and the endoplasmic reticulum stress
      signaling pathways in isoliquiritigenin-induced apoptosis of HeLa cell.
AB  - OBJECTIVE: Isoliquiritigenin (ISL), a licorice chalconoid, is considered to be a
      bioactive agent with chemopreventive potential. This study investigates the
      mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa
      cells. METHODS: Cell viability was evaluated using a 3-(4, 5-dimethylthiazol-2
      yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis was determined by
      flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracellular
      ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The
      mitochondrial membrane potential was measured with the dual-emission potential
      sensitive probe 5, 5', 6, 6'-tetra-chloro-1, 1', 3, 3'-tetraethyl
      imidacarbocyanine iodide (JC-1). The degradation of poly-ADP-ribose polymerase
      (PARP) protein, the phosphorylation of PKR-like ER kinase (PERK), the
      phosphorylation of the alpha-subunit of eukaryotic initiation factor 2
      (eIF2alpha), the expression of the 78 kD glucose-regulated protein (GRP 78), and
      the activation of caspase-12 were analyzed via western blot analysis. RESULTS:
      ISL significantly inhibited the proliferation, the increase in ROS levels and
      apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL
      induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which
      displayed features of mitochondria dependent on apoptotic signals. Besides,
      exposure of HeLa cells to ISL triggered endoplasmic reticulum (ER) stress, as
      indicated by the increase in p-eIF2alpha and GRP78 expression, ER stress
      dependent apoptosis is caused by the activation of ER-specific caspase-12.
      CONCLUSION: The findings from our study suggest that ISL-induced oxidative stress
      causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress
      triggered signaling pathways.

PMID- 23534468
TI  - Increase of TNFalpha-stimulated osteoarthritic chondrocytes apoptosis and
      decrease of matrix metalloproteinases 9 by NF-kappaB inhibition.
AB  - OBJECTIVE: To investigate the in vitro effect of caffeic acid phenethyl ester
      (CAPE), a NF-kappaB inhibitor, on the apoptosis of osteoarthritic (OA)
      chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2
      (MMP-2) and matrix metalloproteinase 9 (MMP-9). METHODS: Annexin V-FITC/propidium
      iodide (PI) labeling and western blotting were used to observe and determine the
      apoptosis in TNFalpha-stimulated primary cultured osteoarthritic chondrocytes.
      Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in
      supernatants. RESULTS: It was confirmed by both flow cytometry and western
      blotting that chondrocytes from OA patients have an apoptotic background. Use of
      CAPE in combination with 10 ng/mL of TNFalpha for 24 h facilitated the apoptosis.
      MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9),
      and the physiologic calcium concentration (2.5 mmol/L) could delay the
      autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh
      supernatant increased significantly in response to stimulation by 10 ng/mL of
      TNFalpha for 24 h. The stimulatory effect of TNFalpha just on proMMP-9 was
      counteracted significantly by CAPE. CONCLUSION: NF-kappaB could prevent
      chondrocytes apoptosis though its activation was attributed to the increase of
      proMMP-9 activity induced by TNFalpha (a pro-apoptotic factor). Therefore,
      therapeutic NF-kappaB inhibitor was a 'double-edged swords' to the apoptosis of
      chondrocytes and the secretion of MMP-9.

PMID- 23534469
TI  - Limb muscle hemodynamics and arterial distensibility depend on atmospheric
      pressure in hypertensive men.
AB  - OBJECTIVE: To verify whether peripheral blood circulation and arterial wall
      distensibility are influenced by atmospheric pressure (AtPr) and to examine if
      their association is dependent on age and/or sex. METHODS: Associations among
      natural AtPr levels (on the examination day as well as 1 and 2 days prior), limb
      muscle hemodynamics, and distensibility of conduit arteries were retrospectively
      examined in an observational study of 276 untreated patients with primary
      moderate hypertension (mean age 56.4 years, 194 men). Forearm and calf
      circulations at rest and 3 min after ischemia were measured by venous occlusion
      plethysmography. Compliance of the brachial and shank arteries was assessed by
      oscillometry. RESULTS: After adjustment for age, degree of hypertension, and
      season, correlation and multiple regression analyses revealed a season
      independent but age-dependent direct correlation between the stiffness of limb
      arteries and AtPr levels on the examination day in men, but not women. The
      association weakened with the degree of hypertension, disappeared with age, and
      was more evident in the arms than in the legs. CONCLUSION: Parameters of arterial
      wall distensibility in adult hypertensive men are susceptible to AtPr changes
      within the usually observed limits (730-770 mmHg). It is proposed that reduction
      of arterial wall barometric responsiveness in women and aging men is a likely
      mechanism underlying their meteosensitivity.

PMID- 23534470
TI  - Protective effect of Coleus aromaticus Benth (Lamiaceae) against naphthalene
      induced hepatotoxicity.
AB  - OBJECTIVE: To investigate protective effect of Coleus aromaticus leaf extract
      against naphthalene induced hepatotoxicity in rats. METHODS: Eighteen male rats
      were divided into three groups. Group I rats were treated as control. Group II
      rats were intraperitoneally administered with naphthalene (435 mg/kg b.wt)
      dissolved in corn oil once a day for a period of 30 days. Group III rats were
      treated with leaf extract (100 mg/kg b.wt) dissolved in 0.9% saline and
      naphthalene (435 mg/kg b.wt) dissolved in corn oil once a day for a period of 30
      days. RESULTS: Significant protective effect was observed against naphthalene
      induced liver damage, which appeared evident from the response levels of marker
      enzymes (aspartate transaminase, alanine transaminase, acid phosphatase, alkaline
      phosphatase and lactate dehydrogenase). The biochemical components viz.
      triglycerides, free fatty acids, cholesterol acyl transferase, high-density
      lipoprotein, low-density lipoprotein, cholesterol and bilirubin were found to be
      increased in liver and serum of naphthalene stressed rats when compared to
      control. CONCLUSION: Treatment of naphthalene intoxicated rats with plant extract
      reversed these distorted parameters to near normal levels. Liver histology showed
      supportive evidence regarding the protective nature of plant extract against
      fatty changes induced by naphthalene. The present study provides a scientific
      rationale for using C. aromaticus in the management of liver disorders.

PMID- 23534471
TI  - Use of traditional Chinese medicine in Chinese patients with coronary heart
      disease.
AB  - OBJECTIVE: To study the use of traditional Chinese medicine (TCM) or both TCM and
      guideline-recommended Western medicine (WM) in Chinese patients with coronary
      heart disease (CHD). METHODS: A cross-sectional nationwide survey of 2803 CHD
      outpatients was completed by collecting information, including general
      demographic data, disease history, and use of drugs (including TCM and WM).
      RESULTS: Of the 2712 CHD outpatients with complete drug treatment data, only 3.1%
      received TCM without any WM for CHD, 30.0% received both TCM and WM recommended
      by current CHD guidelines, and 66.9% received only WM. Patients with a longer
      history of CHD or with a history of stroke, were more likely to use TCM. However,
      90.6% of CHD patients who used TCM also used certain WM. Furthermore, patients
      who used more types of TCM tended to use much less WM recommended by current
      guidelines. CONCLUSION: A substantial proportion of Chinese CHD outpatients use
      both TCM and WM for secondary prevention of CHD. It is important to assess the
      effect of combined TCM and WM on major clinical outcomes in Chinese CHD patients.

PMID- 23534472
TI  - Copper ameliorates fluoride toxicity in fluoride and molybdenum fed rabbits.

PMID- 23534473
TI  - Combination use of PFGE and drug-resistant analysis in the epidemiological
      investigation of Listeria monocytogenes.

PMID- 23534474
TI  - Expression of recombinant human lysozyme-tachyplesin I (hLYZ-TP I) in Pichia
      pastoris and analysis of antibacterial activity.

PMID- 23534476
TI  - Fontan completions over 10 years after Glenn procedures.
AB  - OBJECTIVE: Despite the broadened indications for Fontan procedure, there are
      patients who could not proceed to Fontan procedure because of the strict Fontan
      criteria during the early period. Some patients suffer from post-Glenn
      complications such as hypoxia, arrhythmia, or fatigue with exertion long after
      the Glenn procedure. We explored the possibility of Fontan completion for those
      patients. METHODS: Between 2004 and 2010, five consecutive patients aged between
      13 and 31 years (median 21) underwent Fontan completion. These patients had been
      followed up for more than 10 years (10 to 13, median 11) after Glenn procedure as
      non-Fontan candidates. We summarise these patients retrospectively in terms of
      their pre-operative physiological condition, surgical strategy, and problems that
      these patients hold. RESULTS: Pre-operative catheterisation showed pulmonary
      vascular resistance ranging from 0.9 to 3.7 (median 2.2), pulmonary to systemic
      flow ratio of 0.3 to 1.6 (median 0.9), and two patients had significant
      aortopulmonary collaterals. Extracardiac total cavopulmonary connections were
      performed in three patients, lateral tunnel total cavopulmonary connection in one
      patient, and intracardiac total cavopulmonary connection in one patient, without
      a surgical fenestration. Concomitant surgeries were required including valve
      surgeries--atrioventricular valve plasty in three patients and tricuspid valve
      replacement in one patient; systemic outflow tract obstruction release--Damus
      Kaye-Stansel procedure in two patients and subaortic stenosis resection in one
      patient; and anti-arrhythmic therapies--maze procedure in two patients,
      cryoablation in two patients, and pacemaker implantation in two patients. All
      patients are now in New York Heart Association category I. CONCLUSION: Patients
      often suffer from post-Glenn complications. Of those, if they are re-examined
      carefully, some may have a chance to undergo Fontan completion and benefit from
      it. Multiple lesions such as atrioventricular valve regurgitation, systemic
      outflow obstruction, or arrhythmia should be surgically repaired concomitantly.

PMID- 23534475
TI  - De novo design of protein kinase inhibitors by in silico identification of hinge
      region-binding fragments.
AB  - Protein kinases constitute an attractive family of enzyme targets with high
      relevance to cell and disease biology. Small molecule inhibitors are powerful
      tools to dissect and elucidate the function of kinases in chemical biology
      research and to serve as potential starting points for drug discovery. However,
      the discovery and development of novel inhibitors remains challenging. Here, we
      describe a structure-based de novo design approach that generates novel, hinge
      binding fragments that are synthetically feasible and can be elaborated to small
      molecule libraries. Starting from commercially available compounds, core
      fragments were extracted, filtered for pharmacophoric properties compatible with
      hinge-region binding, and docked into a panel of protein kinases. Fragments with
      a high consensus score were subsequently short-listed for synthesis. Application
      of this strategy led to a number of core fragments with no previously reported
      activity against kinases. Small libraries around the core fragments were
      synthesized, and representative compounds were tested against a large panel of
      protein kinases and subjected to co-crystallization experiments. Each of the
      tested compounds was active against at least one kinase, but not all kinases in
      the panel were inhibited. A number of compounds showed high ligand efficiencies
      for therapeutically relevant kinases; among them were MAPKAP-K3, SRPK1, SGK1,
      TAK1, and GCK for which only few inhibitors are reported in the literature.

PMID- 23534478
TI  - Quantitative exploration of electron transfer in a single noncovalent
      supramolecular assembly.
AB  - Electron transfer through a noncovalent interaction bears essential relevance to
      the functions of bottom-up supramolecular assembly. However, rather little
      knowledge regarding such phenomena at the single-molecule level is currently
      available. Herein we report the direct quantification of electron-transfer
      processes for a single noncovalently linked porphyrin-fullerene dyad. Facilitated
      electron transfer via a charge-transfer interaction in-between was successfully
      measured by utilizing a fullerene molecular tip. The rectification property of
      the supramolecular assembly was determined and quantitatively assessed. The
      present study opens up a way to explore quantitatively the rich electronic
      properties of supramolecules at the single-molecule level.

PMID- 23534477
TI  - Venue-level correlates of female sex worker registration status: a multilevel
      analysis of bars in Tijuana, Mexico.
AB  - In Tijuana, Mexico, sex work is regulated by the municipal government, through
      registration cards issued to female sex workers (FSWs) for an annual fee.
      Registration has been associated with decreased drug use and increase condom use
      and HIV testing. Previously, it was demonstrated that FSWs operating in bars were
      more likely than street-based FSWs to be registered. This implies that certain
      venues may be more accessible to local authorities for the enforcement of this
      type of programme. Taking a novel multilevel approach, we examined whether venue
      characteristics of bars reflecting greater organised management and visibility
      affect registration status of FSWs. In an analysis of venue-level
      characteristics, predictors of being registered were availability of free condoms
      at work and distance to the main sex strip; however, these were not independently
      associated after inclusion of FSWs' income, illicit drug use and history of HIV
      testing. Our findings suggest that sex work regulations may inadvertently exclude
      venues in which the more vulnerable and less visible FSWs, such as injection drug
      users and those with limited financial resources, are situated. Efforts to revise
      or reconsider sex work regulations to ensure that they best promote FSWs' health,
      human and labour rights are recommended.

PMID- 23534479
TI  - High density intercalation of porphyrin into transparent clay membrane without
      aggregation.
AB  - Cationic porphyrin was successfully intercalated into transparent clay membrane
      by developing the new strategy for the sample preparation conditions. When
      water:ethanol = 1:2 (v:v) was used as solvent for porphyrin penetration process,
      high density intercalation of porphyrin into the clay membrane was achieved. In
      the interlayer space, porphyrin molecules do not aggregate owing to intercharge
      distance matching effect (size-matching effect), even at high density condition.
      Judging from XRD and absorption measurements, the orientations of the porphyrins
      in the clay layers should be almost parallel to the clay nanosheet as monolayer.
      Because the fluorescence quantum yield did not depend on its loading level, it is
      turned out that intercalated TMPyP in the clay film keeps the photoactivity even
      under the high density conditions.

PMID- 23534480
TI  - Kinetics of photon upconversion in ionic liquids: time-resolved analysis of
      delayed fluorescence.
AB  - Photon upconversion (UC) based on triplet-triplet annihilation (TTA) is an
      emerging wavelength shifting technology, which is applicable to sunlight.
      Previously we found that the quantum efficiency of TTA-UC (PhiUC) carried out in
      ionic liquids (ILs) is dependent on the type of IL employed. In this article we
      investigate the kinetics of the triplet emitter molecules (perylene) that
      implement TTA to determine the origin of the IL dependence of PhiUC. We measure
      the time-resolved delayed UC fluorescence intensities from samples made with five
      imidazolium-based ILs, and their intensity decay curves are analyzed with an
      analytical model. Consequently, several important aspects regarding both the
      first-order and second-order decays are elucidated. It is revealed that the IL
      dependence of PhiUC primarily originates from the IL dependence of the branching
      ratio toward TTA upon an encounter of two triplet emitter molecules.
      Additionally, a strong correlation between the viscosity of the ILs and the
      branching ratios toward TTA is found. This finding is supported by temperature
      dependent measurements, from which PhiUC is found to be significantly affected by
      the viscosity of the IL. The results of this study should provide a clue for
      further improving PhiUC.

PMID- 23534481
TI  - Impaired heme oxygenase-1 induction in the gastric antrum induces disruption of
      the interstitial cells of Cajal network in a rat model of streptozotocin-induced
      diabetes.
AB  - BACKGROUND: Streptozotocin (STZ) is known to induce type I diabetes and the loss
      of the interstitial cells of Cajal (ICC). However, the regulation of heme
      oxygenase-1 (HO-1) expression, which is reported to protect ICC, has not yet been
      elucidated in this model. The aim of this study was to investigate the
      alterations of HO-1 expression and clarify the mechanism of ICC loss in the
      stomach using the rat model of STZ-induced diabetes. METHODS: Streptozotocin (65
      mg kg(-1) ) was intraperitoneally administered to 8-week-old female Wistar rats.
      Cobalt protoporphyrin (CoPP), an HO-1 inducer, was administered subcutaneously
      once a week after the STZ injection. The expressions of HO-1 and the receptor
      tyrosine kinase c-Kit (a marker for ICC) proteins were investigated by western
      blot analysis and immunofluorescence staining. KEY RESULTS: Expression of c-Kit,
      particularly in the gastric antrum, was significantly decreased at 8 weeks, not
      at 1 week, compared to those of the control group. Significantly increased
      induction of HO-1 expression, especially in the gastric corpus but not in the
      antrum, was observed in the STZ group at 8 weeks after the STZ injection relative
      to control. CoPP administration significantly up-regulated HO-1 expression in the
      STZ diabetic group and significantly restored the previously reduced ICC in the
      gastric antrum. CONCLUSIONS & INFERENCES: Up-regulation of HO-1 expression in the
      STZ diabetic model was limited to the gastric corpus and impaired up-regulation
      of HO-1 expression in the gastric antrum likely induced the disruption of the ICC
      network.

PMID- 23534482
TI  - Early outcomes of liver transplants in patients receiving organs from
      hypernatremic donors.
AB  - OBJECTIVES: Uncorrected hypernatremia in organ donors has been associated with
      poor graft or patient survival during liver transplants. However, recent studies
      have found no association between the donor serum sodium and transplant outcome.
      This study sought to show the negative effect donor hypernatremia has on initial
      liver allograft function. This is the first study to investigate international
      normalized ratio and renal factors of patients with normal and those with
      hypernatremic donor livers. MATERIALS AND METHODS: This study was conducted at
      the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July
      2011. Four hundred seven consecutive adult orthotopic liver transplants were
      performed at the University of Shiraz Medical Center. RESULTS: There were 93
      donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or
      greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group
      2). Posttransplant data after 5 days showed that aspartate aminotransferase,
      alanine aminotransferase, international normalized ratio, and kidney function did
      not differ between the groups. CONCLUSIONS: Hypernatremia is the most important
      complication after brain death. Previous studies have suggested donor
      hypernatremia results in a greater incidence of early postoperative graft
      dysfunction in liver transplant and is considered one of the extended criteria
      donor. However, in recent years, this hypothesis has been questioned. Our study
      shows no difference between patients' initial results of liver and kidney
      functioning with normal and hypernatremic donor livers. This is the first study
      to investigate international normalized ratio as a fundamental factor in defining
      early allograft dysfunction and renal factors between patients with normal and
      hypernatremic donor's livers.

PMID- 23534483
TI  - Atropisomeric dihydroanthracenones as inhibitors of multiresistant Staphylococcus
      aureus.
AB  - Two bisdihydroanthracenone atropodiastereomeric pairs, including homodimeric
      flavomannin A (1) and the previously unreported flavomannin B (2), two new
      unsymmetrical dimers (3 and 4), and two new mixed
      dihydroanthracenone/anthraquinone dimers (5 and 6) were isolated from Talaromyces
      wortmannii , an endophyte of Aloe vera . The structures of 2-6 were elucidated by
      extensive NMR and mass spectrometric analyses. The axial chirality of the biaryls
      was determined using TDDFT ECD and VCD calculations, the combination of which
      however did not allow the assignment of the central chirality elements of 1. The
      compounds exhibited antibacterial activity against Staphylococcus aureus ,
      including (multi)drug-resistant clinical isolates. Reporter gene analyses
      indicated induction of the SOS response for some of the derivatives, suggesting
      interference with DNA structure or metabolism. Fluorescence microscopy
      demonstrated defective segregation of the bacterial chromosome and DNA
      degradation. Notably, the compounds showed no cytotoxic activity, encouraging
      their further evaluation as potential starting points for antibacterial drug
      development.

PMID- 23534484
TI  - Serratia marcescens associated ampullary system infection and septicaemia in a
      bonnethead shark, Sphyrna tiburo (L.).

PMID- 23534485
TI  - Microwave detection of sulfoxylic acid (HOSOH).
AB  - Sulfoxylic acid (HOSOH), a chemical intermediate roughly midway along the path
      between highly reduced (H2S) and highly oxidized sulfur (H2SO4), has been
      detected using Fourier transform microwave spectroscopy and double resonance
      techniques, guided by new high-level CCSD(T) quantum-chemical calculations of its
      molecular structure. Rotational spectra of the two most stable isomers of HOSOH,
      the putative ground state with C2 symmetry and the low-lying C(s) rotamer, have
      been measured to high precision up to 71 GHz, allowing accurate spectroscopic
      parameters to be derived for both isomers. HOSOH may play a role in atmospheric
      and interstellar chemistry, and the present work provides the essential data to
      enable remote sensing and/or radioastronomical searches for these species.
      Spectroscopic characterization of HOSOH suggests that other transient
      intermediates in the oxidation of SO2 to H2SO4 may be amenable to laboratory
      detection as well.

PMID- 23534486
TI  - Quantitative analysis of oligosaccharides derived from sulfated
      glycosaminoglycans by nanodiamond-based affinity purification and matrix-assisted
      laser desorption/ionization mass spectrometry.
AB  - Degraded fragments of sulfated glycosaminoglycans (GAGs) are key reporters for
      profiling the burden of mucopolysaccharidosis (MPS) disease at baseline and
      during therapy. Here, we present a high-throughput assay, which combines
      microwave-assisted degradation, solid-phase affinity purification, and matrix
      assisted laser desorption/ionization mass spectrometry (MALDI MS), for
      quantitative analysis of sulfated oligosaccharides in biological samples. First,
      sulfated oligosaccharides such as chondroitin-4-sulfate (CS) were efficiently
      isolated from highly diluted solutions or spiked artificial cerebrospinal fluid
      (aCSF) using polyarginine-coated nanodiamonds (PA-coated NDs) as affinity
      sorbents. Next, they were degraded to disaccharides through microwave-assisted
      methanolysis or enzymatic digestion for subsequent MALDI-TOF MS analysis. The
      reaction times for GAG depolymerization were significantly reduced from a few
      hours to less than 7 min under the microwave irradiation. Deuterium-labeled
      internal standards were then mixed with the CS-derived disaccharides for
      quantitative analysis by MALDI-TOF MS using the N-(1-naphthyl) ethylenediamine
      dihydrochloride (NEDC) matrix. The new assay is facile, specific (with distinct
      chlorine-isotope trait markers), sensitive (with a detection limit of ~70 pg),
      and potentially useful for clinical diagnosis of MPS.

PMID- 23534489
TI  - Cr(VI) trioxide as a starting material for the synthesis of novel zero-, one-,
      and two-dimensional uranyl dichromates and chromate-dichromates.
AB  - Six different dichromate-based uranyl compounds were obtained. Their structures
      belong to four principally different but related structure types with different
      dimensionality of basic structural units. The units in Cs2(UO2)(Cr2O7)(NO3)2 (1)
      and (C6H11N2)2(UO2)(Cr2O7)2(H2O) (2) are unique, and these are the first "pure"
      uranyl-dichromates known to date. The compounds Rb2(UO2)(CrO4)(Cr2O7) (3),
      (C2NH8)2(UO2)(CrO4)(Cr2O7) (4), (C2NH8)2(UO2)(CrO4)2(Cr2O7)(H2O)2 (5), and
      (C3NH10)2(UO2)(CrO4)2(Cr2O7)(H2O)2 (6) are novel representatives of a rather
      small group of inorganic compounds containing both isolated CrO4 tetrahedra and
      dichromate Cr2O7 groups. The structures of 5 and 6 contain compositionally
      identical but topologically different infinity(2)[(UO2)(CrO4)2(Cr2O7)](2-) sheets
      (thus corresponding to different geometrical isomers), which have not been
      reported previously in inorganic compounds. All novel phases have been prepared
      with an excess of CrO3. "Pure" dichromates are formed at pH < 1.5 and with prior
      hydrothermal treatment of uranyl-chromate solution, whereas mixed chromate
      dichromates are formed at higher pH > 2 values.

PMID- 23534487
TI  - Impacts of a prekindergarten program on children's mathematics, language,
      literacy, executive function, and emotional skills.
AB  - Publicly funded prekindergarten programs have achieved small-to-large impacts on
      children's cognitive outcomes. The current study examined the impact of a
      prekindergarten program that implemented a coaching system and consistent
      literacy, language, and mathematics curricula on these and other nontargeted,
      essential components of school readiness, such as executive functioning.
      Participants included 2,018 four and five-year-old children. Findings indicated
      that the program had moderate-to-large impacts on children's language, literacy,
      numeracy and mathematics skills, and small impacts on children's executive
      functioning and a measure of emotion recognition. Some impacts were considerably
      larger for some subgroups. For urban public school districts, results inform
      important programmatic decisions. For policy makers, results confirm that
      prekindergarten programs can improve educationally vital outcomes for children in
      meaningful, important ways. 

PMID- 23534490
TI  - An applicable strategy for improvement recovery in simultaneous analysis of 20
      pesticides residue in tea.
AB  - It is important to have a reliable method to analyze pesticides in tea, a
      beverage commonly consumed in Iran. A validated method was developed for the
      determination of 20 pesticides in tea based on QuEChERS sample preparation and
      capillary gas chromatography-quadrupole mass spectrometry in selective ion
      monitoring mode (GC-MS/SIM) using triphenyl methane (TPM) solution as an internal
      standard. We used fortified, extracted, and cleaned-up tea samples instead of
      calibration standards for quantitation, which substantially reduced adverse
      matrix-related effects and negative recovery affected by graphite carbon black
      (GCB) on pesticide analysis. The recovery of pesticides at 3 concentration (40,
      60, and 240 ng/g) ranged from 79.5% to 111.4% (n = 3). The method had acceptable
      repeatability with RSDr < 20%. The limits of quantification (LOQ) for all
      pesticides were <=20 ng/g. The analytical results of the proposed method were in
      good agreement with proficiency test results (FAPAS, 19116). The recoveries and
      repeatabilities were in accordance with the criteria set by SANCO Guideline. The
      validated method was suitable for the analysis of pesticides in tea.

PMID- 23534491
TI  - Matrix structure selection in the microparticles of essential oil oregano
      produced by spray dryer.
AB  - The goal of this work was to select the best combination of encapsulants for the
      microencapsulation of oregano essential oil by spray dryer with the addition of
      Arabic gum (AG), modified starch (MS) and maltodextrin (MA). The simplex-centroid
      method was used to obtain an optimal objective function with three variables.
      Analytical methods for carvacrol quantification, water activity, moisture
      content, wettability, solubility, encapsulation efficiency (ME) and oil retention
      (RT) were used to evaluate the best combination of encapsulants. The use of AG as
      a single wall material increased ME up to 93%. Carvacrol is the major phenolic
      compound existent in the oregano essential oil. Carvacrol exhibits a maximum
      concentration of 57.8% in the microparticle with the use of 62.5% AG and 37.5%
      MA. A greater RT (77.39%) was obtained when 74.5% AG; MS 12.7% and 12.7% MA were
      applied, and ME (93%) was improved with 100% of gum.

PMID- 23534492
TI  - Topical delivery of enoxaparin using nanostructured lipid carrier.
AB  - Topical application of enoxaparin (ENX; low molecular weight heparin) prevents
      the occurrence of thrombosis at traumatic anastomosis site. Particulate carrier
      system like nanostructured lipid carriers (NLCs) could notably improve skin
      penetration of ENX. ENX-loaded NLCs were prepared by the solvent diffusion
      technique. The effect of formulation and process variables on the physicochemical
      properties of prepared NLCs was studied and characterized. In vitro skin
      permeation studies revealed better passage of enoxaparin by NLCs than of plain
      drug. The in vivo skin retention was monitored by fluorescence microscopy. The
      prepared NLCs when stored for 120 days were found to be more stable at 4 +/- 2 
      degrees C than room temperature. The overall results of the study demonstrated
      the importance of carrier composition on the physicochemical properties,
      morphology, skin irritation and consequently the effectiveness of particulate
      system as a vehicle for topical delivery of enoxaparin.

PMID- 23534493
TI  - The effect of homogenization method on the properties of carbamazepine
      microparticles prepared by spray congealing.
AB  - Abstract The aim of this study was to investigate the influence of ultrasound and
      high-shear mixing on the properties of microparticles obtained by spray
      congealing. Dispersions containing 10% carbamazepine and 90% carrier Gelucire(r)
      50/13 (w/w) were prepared using magnetic stirring, high-shear mixing, or
      ultrasound. Each preparation was made using hot-melt mixing spray congealing to
      obtain the microparticles. All microparticles presented a spherical shape with
      high encapsulation efficiency (>99%). High-shear mixing and ultrasound promoted a
      decrease in the size of microparticles (D90) to 62.8 +/- 4.1 MUm and 64.9 +/- 3.3
      MUm, respectively, while magnetic stirring produced microparticles with a size of
      84.1 +/- 1.4 um. The use of ultrasound led to microparticles with increased
      moisture content as identified through sorption isotherm studies. In addition,
      rheograms showed distinct rheological behaviour among different dispersion
      preparations. Therefore, the technique used to prepare dispersions for spray
      congealing can affect specific characteristics of the microparticles and should
      be controlled during the preparation. 

PMID- 23534494
TI  - Development of doxorubicin loaded novel core shell structured nanocapsules for
      the intervention of visceral leishmaniasis.
AB  - The aim of this study was to develop novel nanoemuslion core loaded nanocapsules
      (NCs) with high payload of doxorubicin (DOX) and to assess its efficacy against
      Leishmania donovani. The low energy emulsification method was used to obtained
      nanoemulsion core as template, followed by stepwise addition of additional layer
      components protamine sulphate and sodium alginate. Zeta potential studies
      revealed that there was reversal in charge after each layering. NCs were
      characterized on the basis of size (340 nm) and entrapment efficiency (>80%). The
      drug release behaviour was studied by in vitro method. The NCs loaded with DOX
      (NCs-DOX) is completely internalized into macrophages showing improved efficacy
      (IC50 of formulation is almost <= 1.9-fold as compared to plain drug, p < 0.05)
      against intracellular amastigotes. 

PMID- 23534495
TI  - Effective parameters in determining cross-linked dextran microsphere
      characteristics: screening by Plackett-Burman design-of-experiments.
AB  - This study aims to screen the effective parameters in preparing cross-linked
      dextran microspheres (CDMs) to make them controllable for obtaining microspheres
      with tunable properties. Microspheres were prepared by chemical crosslinking of
      dextran dissolved in internal phase of an inverse emulsion system (W/O) using
      epichlorohydrin (ECH). A Plackett-Burman design-of-experiments was employed as
      the screening methodology to investigate the effects of the kinetics and process
      parameters, i.e. the mixing speed and emulsification time on the resulting
      microsphere characteristics. Crosslinking reaction temperature and concentrations
      of the emulsion constituents including dextran, ECH and sodium hydroxide were the
      studied kinetic parameters. Equilibrium swelling ratio, mean particle size and
      size distribution of the resulting CDMs were measured and statistically analysed.
      It was found that dextran concentration is the most influential parameter on the
      particle size and swelling ratio of the obtained CDMs. Increasing dextran
      concentration in the aqueous phase leads to a significant increase in the mean
      particle size and decrement in water uptake capacity of the resulting
      microspheres, respectively. 

PMID- 23534496
TI  - Compromised quality of life in patients with both Type 1 diabetes mellitus and
      coeliac disease.
AB  - AIMS: Type 1 diabetes mellitus and coeliac disease are two chronic illnesses
      associated with each other. Both diseases and their treatments can seriously
      impair quality of life. The objective of the present study was to investigate
      health-related quality of life in adult patients diagnosed with both Type 1
      diabetes and coeliac disease and compare this with healthy control subjects and
      control subjects who have Type 1 diabetes only. METHODS: A generic measure of
      health-related quality of life (RAND-36) and a measure of diabetes-specific
      quality of life (DQOL) questionnaires were sent to patients diagnosed with both
      Type 1 diabetes and coeliac disease. The control group consisted of patients with
      Type 1 diabetes without coeliac disease matched for age, gender and socio
      economic status. Generic quality of life scores were compared with data from
      healthy Dutch control subjects. RESULTS: Fifty-seven patients with Type 1
      diabetes and coeliac disease were included and no associations between clinical
      characteristics and quality of life were observed. Women reported a lower quality
      of life in social functioning, vitality and mental health than men (all P <
      0.05). A lower diabetes-specific quality of life was observed regarding diabetes
      related worries and social worries in patients with Type 1 diabetes and coeliac
      disease compared with patients with Type 1 diabetes. Compared with healthy
      control subjects, quality of life in patients with Type 1 diabetes and coeliac
      disease was significantly lower, particularly social functioning (Cohen's d =
      0.76) and general health perception (Cohen's d = 0.86). CONCLUSIONS: The
      additional diagnosis of coeliac disease and treatment by gluten-free diet in
      adult patients with Type 1 diabetes has a considerable, negative impact on
      quality of life and diabetes-specific quality of life. Women are particularly
      affected and social functioning and general health perception is compromised.

PMID- 23534497
TI  - Genotoxicity and antioxidant enzyme activity induced by hexavalent chromium in
      Cyprinus carpio after in vivo exposure.
AB  - Fish, being an important native of the aquatic ecosystem, are exposed to
      multipollution states and are therefore considered as model organisms for
      ecotoxicological studies of aquatic pollutants, including metal toxicity. We
      investigated oxidative stress (OS) in liver, kidney and gill tissues through
      antioxidant enzyme activities and genotoxicity induced in whole blood and gill
      tissues through comet assay and micronucleus (MN) test in Cyprinus carpio after
      96-hour in vivo static exposure to potassium dichromate at three sublethal (SL)
      test concentrations, including SL-I [93.95 mg/L, i.e. one quarter of half-maximal
      lethal concentration (LC50)], SL-II (187.9 mg/L, i.e. one half of LC50), and SL
      III (281.85 mg/L, i.e. three quarters of LC50), along with a control. The 96-hour
      LC50 value for potassium dichromate was estimated to be 375.8 mg/L in a static
      system in the test species. Tissues samples were collected at 24, 48, 72 and 96
      hours postexposure. Results indicated that the exposed fish experienced OS as
      characterized by significant (p < 0.05) variation in antioxidant enzyme
      activities, as compared to the control. Activities of superoxide dismutase and
      glutathione peroxidase increased, whereas activity of catalase decreased with the
      progression of the experiment. The mean percent DNA damage in comet tail and MN
      induction in gills and whole blood showed a concentration-dependent increase up
      to 96-hour exposure. The findings of this study would be helpful in organ
      specific risk assessment of Cr(VI)-induced OS and genotoxicity in fishes.

PMID- 23534498
TI  - Gastric emptying of solids and its relationship with microalbuminuria in children
      and adolescents with type 1 diabetes mellitus.
AB  - BACKGROUND: The aims of the present study were to determine the frequency of
      delayed gastric emptying in children and adolescents with type 1 diabetes
      mellitus (T1DM) and to investigate the relationship between gastric emptying rate
      and other contributing factors (e.g. serum HbA1c, duration of diabetes and
      microalbuminuria) in these patients. METHODS: This was a clinical trial
      evaluating the rate of gastric emptying of solid meals in 33 children and
      adolescents with T1DM and in 26 healthy peers using a radionuclide method. Three
      consecutive overnight urine collections were used to calculate the albumin
      excretion rate. RESULTS: There was no significant difference in the gastric half
      emptying time (GE t1/2 ) between patients and controls (151.7 +/- 154.5 vs 109.8
      +/- 60.5 min, respectively; P=0.885) or the frequency of delayed gastric emptying
      (36.4% vs 30.8%, respectively; P=0.433). There was a moderately positive
      correlation between GE t1/2 and the duration of diabetes (r=0.380; P=0.029).
      There was no correlation between GE t1/2 and microalbumin levels in T1DM
      patients. In these patients, the body mass index standard deviation scores were
      significantly lower than in patients with normal gastric emptying (-0.13 +/- 0.87
      vs 0.7 +/- 1.23, respectively; P=0.044). CONCLUSION: Progression of delayed
      gastric emptying is more likely to be related to a longer duration of diabetes
      than glycemic control in children and adolescents with T1DM. Patients with
      delayed gastric emptying are thinner compared with patients with a normal rate of
      gastric emptying; they may also be asymptomatic.

PMID- 23534499
TI  - Variation in height and BMI of adult Indians.
AB  - It is well known that height and weight are interrelated, and that both are
      related to socioeconomic variables. The objective of this study was to assess the
      effect of socioeconomic variables on the heights and weights of different groups
      of people, formed according to different levels of heights and weights, and to
      see whether there are sex differences in the variations in heights and weights.
      Data for adults aged 15-49 years were taken from the India National Family Health
      Survey-3 and descriptive studies and multiple linear regression analyses carried
      out. A clear positive association was found for height and BMI with economic
      level (except for overweight females in the case of BMI). In the case of BMI, it
      is age that seems to be the most influential factor. Surprisingly, the observed
      changes in height and BMI are not as expected for short and tall or underweight
      and overweight people; these sometimes behave in the opposite directions to that
      of normal height and weight people. The basic assumption of multivariate
      normality is not valid due to changing relations at different height and BMI
      levels.

PMID- 23534500
TI  - Oxidative para-triflation of acetanilides.
AB  - Direct triflation of acetanilide derivatives with silver triflate has been
      accomplished under mild iodine(III)-mediated oxidative conditions. The reaction
      shows excellent regioselectivity for the para position and tolerates a range of
      ortho and meta substituents on the aromatic ring. This method is also compatible
      with the preparation of arylnonaflates in synthetically useful yields.

PMID- 23534501
TI  - Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary
      Cooperative Oncology Group (VCOG) consensus document.
AB  - In veterinary medical oncology, there is currently no standardized protocol for
      assessing response to therapy in solid tumours. The lack of such a formalized
      guideline makes it challenging to critically compare outcome measures across
      various treatment protocols. The Veterinary Cooperative Oncology Group (VCOG)
      membership consensus document presented here is based on the recommendations of a
      subcommittee of American College of Veterinary Internal Medicine (ACVIM) board
      certified veterinary oncologists. This consensus paper has used the human
      response evaluation criteria in solid tumours (RECIST v1.1) as a framework to
      establish standard procedures for response assessment in canine solid tumours
      that is meant to be easy to use, repeatable and applicable across a variety of
      clinical trial structures in veterinary oncology. It is hoped that this new
      canine RECIST (cRECIST v1.0) will be adopted within the veterinary oncology
      community and thereby facilitate the comparison of current and future treatment
      protocols used for companion animals with cancer. 

PMID- 23534502
TI  - Cardiovascular disease in low- and middle-income countries: an urgent priority.

PMID- 23534503
TI  - Culture, ethnicity and chronic conditions: reframing concepts and methods for
      research, interventions and policy in low- and middle-income countries.

PMID- 23534504
TI  - Differences in working conditions and employment arrangements among migrant and
      non-migrant workers in Europe.
AB  - OBJECTIVE: To determine migrant workers' exposure to select occupational risks
      and compare it with that of non-migrant workers in Europe. DESIGN: Based on the
      European Working Conditions Survey (EWCS-2005, n=29,654 workers, 31 countries) we
      examined differential prevalence amongst migrant and non-migrant workers' primary
      paid jobs in terms of employment arrangements (working >10 hours/day, working >5
      days/week, on Sundays, without a contract, changes in the work schedule and not
      free to decide when to take holidays or days off) and working conditions
      (exposure to hazards including chemical, physical agents, physical load and
      psychological conditions). For the purpose of this study, a migrant is defined as
      a person without nationality of the country of residence (n=926). Adjusted
      prevalence ratios (aPRs) for age, economic sector and education were calculated.
      RESULTS: Differences in employment arrangements and working conditions were noted
      by migration status, gender and occupational status. Among non-manual workers,
      migrant males are more exposed than non-migrant males to negative psychosocial
      conditions--working at a very high speed (aPR 1.23; 95% CI 1.07-1.42) and shift
      work (aPR 1.66; 95% CI 1.27-2.17)--and adverse employment arrangements: working
      on Sundays (aPR 1.91; 95% CI 1.42-2.55), variable starting/finishing times (aPR
      1.17; 95% CI 1.04-1.32) and changes in work schedule (aPR 1.56; 95% CI 1.30
      1.88). Compared with non-migrant males, male migrant manual workers are the group
      with a greater number of disparities in terms of exposure to negative working
      conditions. Female migrant non-manual workers are more exposed to psychosocial
      conditions - working at very high speed (aPR 1.26; 95% CI 1.10-1.44) and shift
      work (aPR 1.61; 95% CI 1.29-2.01) while female manual migrant workers were more
      likely to report standing or walking (aPR 2.43; 95% CI 1.98-2.97), not having a
      contract (aPR 2.94; 95% CI 2.07-4.10) and not being free to decide days off and
      holidays (aPR 1.25; 95% CI 1.07-1.48) than non-migrants. CONCLUSION: Migrant
      workers across Europe are more likely to be exposed to certain working and
      employment arrangements that may place them at higher risk of future health
      problems.

PMID- 23534505
TI  - Ethnicity and cardiovascular health research: pushing the boundaries by including
      comparison populations in the countries of origin.
AB  - Chronic diseases such as cardiovascular diseases (CVD) are major health problems
      in most ethnic minority and migrant populations living in high income countries.
      By the same token, CVD is a looming threat that is creating a double burden in
      most of the countries where these populations originate from. The causes of the
      rising burden are unclear, but they are likely to be multifaceted. Traditionally,
      ethnicity and health research have mostly concentrated on comparing the health of
      ethnic minority groups with the majority populations of the countries in which
      they live. This is an important area of research which illuminates ethnic
      inequalities in health. However, a few studies on international comparisons show
      that a lot can be learned from comparing similar ethnic groups living in
      different industrialised countries. Equally, comparing ethnic minority and
      migrant populations to similar populations in their countries of origin will
      generate new knowledge about factors that predispose them to poor health
      outcomes. Thus, to make progress in the field of ethnicity and health research,
      we need a new conceptual framework that simultaneously studies migrant/ethnic
      groups in the country of settlement, in similar countries of settlement, and in
      the countries of ancestral origin. Such studies need to go beyond the commonest
      design of cross-sectional studies to include more cohort studies, interventions
      and linkage studies. This article discusses (1) the burden of CVD in ethnic
      minority and migrant populations; (2) approaches to understanding predisposing
      factors; and (3) application of the results to give insight into the potential
      threats that their countries of origin are likely to face.

PMID- 23534506
TI  - Explanatory models of hypertension among Nigerian patients at a University
      Teaching Hospital.
AB  - OBJECTIVE: To elicit the explanatory models (EM) of hypertension among patients
      in a hospital-based primary care practice in Nigeria. Design. Semi-structured in
      depth individual interviews and focus groups were conducted with 62 hypertensive
      patients. Interviews and focus groups were audiotaped and transcribed verbatim.
      Data analysis was guided by phenomenology and content analysis using qualitative
      research software ATLAS.ti 5.0. RESULTS: Patients expressed four categories of EM
      of hypertension: (1) perceptions of hypertension, (2) consequences, (3) effect on
      daily life, and (4) perception of treatment. Focus group discussions and
      individual interviews yielded a wide range of insights into the social and
      cultural factors influencing patients' beliefs and health behavior. Participants
      were aware of the risks of hypertension. There was disagreement between
      participants' own understanding of the serious nature of hypertension, the need
      for long-term treatment, and the desire to take long-term medication.
      Participants acknowledged the use of traditional medicine (e.g., teas and herbs)
      and healers. Different themes emerged for men versus women such that women often
      focused on family issues while men tended to discuss external stressors stemming
      from work as a cause of hypertension. Men were concerned with frequent urination,
      decreased libido, and erectile dysfunction. CONCLUSION: Knowledge gained will
      inform development of patient-centered treatment plans and targeted behavioral
      and educational interventions.

PMID- 23534507
TI  - Coping and chronic psychosocial consequences of female genital mutilation in The
      Netherlands.
AB  - OBJECTIVE: The study presented in this article explored psychosocial and
      relational problems of African immigrant women in The Netherlands who underwent
      female genital mutilation/cutting (FGM/C), the causes they attribute to these
      problems--in particular, their opinions about the relationship between these
      problems and their circumcision--and the way they cope with these health
      complaints. DESIGN: This mixed-methods study used standardised questionnaires as
      well as in-depth interviews among a purposive sample of 66 women who had migrated
      from Somalia, Sudan, Eritrea, Ethiopia or Sierra Leone to The Netherlands. Data
      were collected by ethnically similar female interviewers; interviews were coded
      and analysed by two independent researchers. RESULTS: One in six respondents
      suffered from post-traumatic stress disorder (PTSD), and one-third reported
      symptoms related to depression or anxiety. The negative feelings caused by FGM/C
      became more prominent during childbirth or when suffering from physical problems.
      Migration to the Netherlands led to a shift in how women perceive FGM, making
      them more aware of the negative consequences of FGM. Many women felt ashamed to
      be examined by a physician and avoided visiting doctors who did not conceal their
      astonishment about the FGM. CONCLUSION: FGM/C had a lifelong impact on the
      majority of the women participating in the study, causing chronic mental and
      psychosocial problems. Migration made women who underwent FGM/C more aware of
      their condition. Three types of women could be distinguished according to their
      coping style: the adaptives, the disempowered and the traumatised. Health care
      providers should become more aware of their problems and more sensitive in
      addressing them.

PMID- 23534508
TI  - Control activity of yeast geranylgeranyl diphosphate synthase from dimer
      interface through H-bonds and hydrophobic interaction.
AB  - Previously we showed that yeast geranylgeranyl diphosphate synthase (GGPPS)
      becomes an inactive monomer when the first N-terminal helix involved in
      dimerization is deleted. This raises questions regarding why dimerization is
      required for GGPPS activity and which amino acids in the dimer interface are
      essential for dimerization-mediated activity. According to the GGPPS crystal
      structure, three amino acids (N101, N104, and Y105) located in the helix F of one
      subunit are near the active site of the other subunit. As presented here, when
      these residues were replaced individually with Ala caused insignificant activity
      changes, N101A/Y105A and N101A/N104A but not N104A/Y105A showed remarkably
      decreased k(cat) values (200-250-fold). The triple mutant N101A/N104A/Y105A
      displayed no detectable activity, although dimer was retained in these mutants.
      Because N101 and Y105 form H-bonds with H139 and R140 in the other subunit,
      respectively, we generated H139A/R140A double mutant and found it was inactive
      and became monomeric. Therefore, the multiple mutations apparently influence the
      integrity of the catalytic site due to the missing H-bonding network. Moreover,
      Met111, also on the highly conserved helix F, was necessary for dimer formation
      and enzyme activity. When Met111 was replaced with Glu, the negative-charged
      repulsion converted half of the dimer into a monomer. In conclusion, the H-bonds
      mainly through N101 for maintaining substrate binding stability and the
      hydrophobic interaction of M111 in dimer interface are essential for activity of
      yeast GGPPS.

PMID- 23534509
TI  - Heparin-binding epidermal growth factor-like growth factor protects rat intestine
      after portal triad clamping.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent
      mitogen and chemotactic factor. HB-EGF attenuates intestinal ischemia/reperfusion
      injury caused by superior mesenteric artery occlusion. We examined whether HB-EGF
      offers protection against intestinal congestion/reperfusion (C/R) injury, which
      is caused by portal triad clamping. Male Sprague-Dawley rats were randomly
      divided into three equally sized groups: I, sham-operated; II, portal triad
      clamping (Pringle maneuver); III, II + intraluminal administration of HB-EGF.
      Compared with sham-operated rats, all rats in group II exhibited significant
      increases in intestinal histologic injury, pro-inflammatory cytokine expression,
      myeloperoxidase activity, malonaldehyde levels, and apoptosis indices.
      Intraluminal administration of HB-EGF in group III significantly reduced these
      indicators when compared with group II. Clamping of the portal triad followed by
      reperfusion causes intestinal C/R injury and intraluminal administration of HB
      EGF reduces the severity of intestinal C/R injury in rats.

PMID- 23534510
TI  - Family needs and involvement in the intensive care unit: a literature review.
AB  - AIMS AND OBJECTIVES: To understand the needs of critically ill patient families',
      seeking to meet those needs and explore the process and patterns of involving
      family members during routine care and resuscitation and other invasive
      procedures. METHODS: A structured literature review using Cumulative Index to
      Nursing and Allied Health Literature, Pubmed, Proquest, Google scholar, Meditext
      database and a hand search of critical care journals via identified search terms
      for relevant articles published between 2000 and 2010. RESULTS: Thirty studies
      were included in the review either undertaken in the Intensive Care Unit or
      conducted with critical care staff using different methods of inquiry. The
      studies were related to family needs; family involvement in routine care; and
      family involvement during resuscitation and other invasive procedures. The
      studies revealed that family members ranked both the need for assurance and the
      need for information as the most important. They also perceived their important
      needs as being unmet, and identified the nurses as the best staff to meet these
      needs, followed by the doctors. The studies demonstrate that both family members
      and healthcare providers have positive attitudes towards family involvement in
      routine care. However, family members and healthcare providers had significantly
      different views of family involvement during resuscitation and other invasive
      procedures. CONCLUSION: Meeting Intensive Care Unit family needs can be achieved
      by supporting and involving families in the care of the critically ill family
      member. More emphasis should be placed on identifying the family needs in
      relation to the influence of cultural values and religion held by the family
      members and the organisational climate and culture of the working area in the
      Intensive Care Unit.

PMID- 23534512
TI  - [Association between plasma leptin level and periodontal parameters in patients
      with aggressive periodontitis].
AB  - OBJECTIVE: To detect the plasma leptin levels in patients with aggressive
      periodontitis (AgP) and to analyze the relationship between circulating leptin
      level and periodontal condition. METHODS: A total of 97 patients with AgP and 44
      healthy controls were recruited. Detailed clinical examinations were conducted
      and clinical parameters such as bleeding index (BI), probing depth (PD),
      attachment loss (AL) were recorded. Plasma leptin level was measured by enzyme
      linked immunosorbent assay. RESULTS: The plasma leptin level in AgP group was
      significantly higher than that of control subjects [(20.0 +/- 4.3) ug/L vs. (7.5
      +/- 1.3) ug/L, P < 0.01)]. The plasma leptin level was positively related to BI,
      PD and AL, and the r values were 0.647, 0.596 and 0.632 respectively (P < 0.01).
      CONCLUSIONS: Plasma leptin concentration in AgP patients was significantly
      elevated compared with healthy controls. Circulating leptin level was positively
      related to periodontal parameters including BI, PD and AL.

PMID- 23534513
TI  - [Evaluation of alveolar bone defect in chronic periodontitis by cone-beam
      computed tomography].
AB  - OBJECTIVE: To evaluate the morphological characteristics of alveolar bone defects
      of the patients with chronic periodontitis using cone-beam CT (CBCT). METHODS:
      Sixty patients with chronic periodontitis were included in this study. CBCT was
      used to scan the alveolar bone and NNT software to measure the alveolar bone
      defects and bone loss types in different regions. RESULTS: Seventy-five percent
      (45/60) of the alveolar bone defect was the generalized type, 25% (15/60) was the
      localized type. In incisor and canine area, the defect of the mandibular alveolar
      bone was more severe than in the same sites of maxilla. There was less bone loss
      in the premolar area of mandible than in the same site of maxilla. In the mesial
      and buccal sites of mandibular molars and in the lingual site of maxillary
      molars, the most severe alveolar bone loss was found. CONCLUSIONS: The obvious
      alveolar bone defect areas in chronic periodontitis were the palatal side of
      maxillary molars and the lingual side of mandibular incisors. CBCT can clearly
      demonstrate the degree of alveolar bone defects in different regions of chronic
      periodontitis.

PMID- 23534514
TI  - [Surgical treatment for hemophilic pseudotumor in maxillofacial region].
AB  - OBJECTIVE: To present 4 cases of hemophilic pseudotumor and to investigate the
      treatment outcome. METHODS: Four cases of hemophilic pseudotumor were reviewed.
      The patients were treated by internal medicine combined with surgery and followed
      up for two years. The feature and diagnosis of the disease were analyzed and the
      treatment outcome was evaluated. RESULTS: All of the 4 cases were misdiagnosed
      with a history of bleeding before operation. One patient was bleeding after
      biopsy without replacement therapy. One patient was presented with gingival
      bleeding and anaemia. The final diagnosis of hemophilia A in all the 4 cases was
      confirmed by the blood test (VIII deficiency). After infusion of factor VIII,
      operation was performed on all cases. There was no recurrence after two years of
      follow-up. CONCLUSIONS: It should be aware of the rarely encountered disease
      which is prone to be misdiagnosed. Under factor-deficient replacement therapy,
      surgical management is the most effective way in preventing from bleeding and
      avoiding progressive expanding of pseudotumor.

PMID- 23534515
TI  - [Clinical evaluation of the five-digit numerical recording system for
      classification of cleft lip and palate deformities].
AB  - OBJECTIVE: To evaluate the five-digit numerical recording system (LAPAL system)
      for classification of cleft lip and palate. METHODS: Fourteen young doctors took
      part in the study after receiving one-hour instruction twice for the LAPAL
      system. Photographs of 200 cases of untreated cleft lip and palate were used for
      the evaluation. The diagnostic codes of the patient were recorded and compared
      with the teacher's standard diagnosis. The basic criterion of the LAPAL system
      was that the clefts were arranged in five anatomical components in order of right
      lip (L), right alveolus and primary palate (A), secondary palate (P), left
      alveolus and primary palate (A), and left lip (L). The degrees of the cleft
      severity were recorded with Arabic number 0 for the intact, 1 for the
      subcutaneous or submucous cleft, 2 for clefts smaller than half of a component, 3
      for clefts larger than half of a component, 4 for complete clefts. RESULTS: The
      rate of the diagnostic coincidence was 88% (2475/2800) totally. The higher
      coincidence appeared in degree 4 of cleft lip and in degree 4 of cleft alveolar
      and cleft primary palate as 99% (707/714) and 100% (546/546), respectively. The
      lower coincidence appeared in degree 2 and degree 3 of clefts of the alveolus and
      primary palate as 70% (98/140) and 82% (103/126), respectively. Among the 17
      types of possible cleft combination, 14 types were found in the present study.
      CONCLUSIONS: The LAPAL system is easily understood and grasped in a short time.
      Clefts on the border of adjoin degrees may cause confusion in diagnosis. More
      training or simplified modification is suggested.

PMID- 23534516
TI  - [Therapeutic mechanism of bleomycin A5 on infancy hemangioma: an experimental
      study].
AB  - OBJECTIVE: To investigate the therapeutic mechanism of Bleomycin A5 on infancy
      hemangioma. METHODS: After intralesional injection of Bleomycin A5 into the tumor
      of animal model of infancy hemangioma, the variation of tumor form was and the
      variation of tumor structure were observed using light microscope and electron
      microscope, the variation of tumor gene expression spectra was also tested by DNA
      microarray technique. RESULTS: After treatment, the tumor gradually shrunk,
      hardened, disappeared one month later. The tumor lost appearance of infancy
      hemangioma and replaced by lamellar collagen fibers and cellular nucleus
      scattered in the fibers, and almost all cells were necrotic and dissolved. Under
      electron microscope, only large stretches of dissolved cell could be seen without
      intact cells and blood vessels, but apoptotic cells and bodies could also be
      found. The results of DNA microarray analysis showed that 9 genes associated with
      apoptosis (murine double minute 2, heat-labile enterotoxin B subunit, lymphotoxin
      B receptor, tumor necrosis factor ligand superfamily 7, tumor necrosis factor
      receptor superfamily 21, tumor necrosis factor receptor superfamily 1A, myeloid
      cell leukemia-1, caspase3), 13 genes associated with cell proliferation and cell
      cycle (cell division cycle27, cell division cycle37, CDC28 protein kinase 1B,
      cycling B1, cullin 2, cullin 3, cullin 4A, growth arrest and DNA damage-inducible
      45A, meiotic recombination 11 homolog B, forkhead box M1, minichromosome
      maintenance 7, antigen identified by monoclonal antibody ki 67, proliferating
      cell nuclear antigen), and 11 genes associated with cellular stress and toxic
      reaction (glutathione peroxidase 1, metallothioneins, superoxide dismutase-1,
      heat shock protein A1A, heat shock protein A2, heat shock protein A4, heat shock
      protein A5, heat shock protein 9B, heat shock protein CA, macrophage migration
      inhibitory factor, plasminogen activator inhibitor)were up or down regulated more
      than 2 folds in tumors treated with Bleomycin A5 compared with controls.
      CONCLUSIONS: The therapeutic effect of Bleomycin A5 on infancy hemangioma is the
      synthetic results of multiple factors. Bleomycin A5 could not only induce
      apoptosis and inhibit cell proliferation, but also depressed the ability of cell
      stress and toxic reaction.

PMID- 23534517
TI  - [Effect of nerve growth factor-gelatin sponge composite on peri-implant
      osseointegration].
AB  - OBJECTIVE: To observe the peri-implant osseointegration after the application of
      exogenous nerve growth factor (NGF)-gelatin sponge (GS) composite. METHODS: Six
      beagle dogs were used to establish bi-mandible simultaneous implant model after
      the first and second premolar extraction. Then the dental implants were implanted
      into the distal socket while the bone defect was made in the mesial socket of
      each mandible. Then the NGF-GS was implanted into the defects as NGF-GS group,
      the gelatin sponge alone was implanted as GS control and the control group was
      left empty. Two dogs were sacrificed each time at 4 weeks, 8 weeks and 12 weeks
      postoperatively. Specimens were subjected to general observation, radiography,
      bone histological and histomorphometric analysis for the new bone formation. The
      data were analyzed with SPSS 11.5 software package. RESULTS: The bone density in
      the defects around implants at 4 and 8 weeks postoperatively was lower than the
      normal bone. The bone-implant contact ratio in the NGF-GS group [(57.7 +/- 6.4)%]
      was significantly higher than that in the GS control group and the control group
      [the ratio were (44.2 +/- 3.3)% and (31.2 +/- 3.1)%] (P < 0.01) at 4 weeks
      postoperatively, the bone-implant contact ratio in the GS control group was also
      significantly higher than that in the control group (P < 0.01) at that time. The
      bone-implant contact ratio in the NGF-GS group [(94.8 +/- 7.7)%] was slightly
      higher than that in the GS control group and the control group [the ratio were
      (83.0 +/- 4.1)% and (86.4 +/- 6.3)%] at 8 weeks postoperatively, but there was no
      statistical difference (P > 0.05). The bone density in the defects around
      implants at 12 weeks was almost the same as the normal bone, there was no
      difference of the bone-implant contact ratio. CONCLUSIONS: NGF-GS application
      could increase new bone formation, accelerate maturation of trabecular bone
      around the implants and shorten the period of osseointegration.

PMID- 23534518
TI  - [Effect of KH2PO4 on the odonto- and osteogenic differentiation potential of
      human stem cells from apical papillae].
AB  - OBJECTIVE: To determine the effects of KH2PO4 on the odonto- and osteogenic
      differentiation potential of human stem cells from apical papillae (SCAP) in
      vitro. METHODS: SCAP were isolated and cultured respectively in alpha minimum
      essential medium (alpha-MEM) or alpha-MEM containing 1.8 mmol/L KH2PO4. Alkaline
      phosphatase (ALP) activity, alizarin red staining, real-time reverse
      transcription polymerase chain reaction (RT-PCR) and Western blotting were used
      to examine the odonto and osteogenic potential of SCAP in the two media. RESULTS:
      SCAP cultured in alpha-MEM containing 1.8 mmol/L KH2PO4 exhibited a higher ALP
      activity [(0.370 +/- 0.013) Sigma unit*min(-1)*mg(-1)] at day 3 than control
      group [(0.285 +/- 0.008) Sigma unit*min(-1)*mg(-1)] and KH2PO4-treated SCAP
      formed more calcified nodules at day 5 [(0.539 +/- 0.007) ug/g] and day 7 [(1.617
      +/- 0.042) ug/g] than those in normal medium [(0.138 +/- 0.037) ug/g, P < 0.01].
      The expression of odonto- and osteogenic markers were significantly up-regulated
      after the stimulation of KH2PO4 at day 3 and 7 respectively, as compared with
      control group. CONCLUSIONS: 1.8 mmol/L KH2PO4 can promote the odonto and
      osteogenic differentiation potential of human SCAP.

PMID- 23534519
TI  - [Effect of the complex of casein phosphopeptide and amorphous calcium phosphate
      on reducing enamel demineralization and promoting remineralization].
AB  - OBJECTIVE: To investigate the effect of the complex of casein phosphopeptide and
      amorphous calcium phosphate (CPP-ACP) on the demineralization and
      remineralization of dental enamel in vitro. METHODS: Premolars extracted from
      patients receiving orthodontic treatment were cut into two slabs, which were
      embedded and polished. The slabs were randomly divided into non-acid etching
      group, acid etching group (immersed in 37.5% phosphoric acid for 2 minutes),
      experimental group A (immersed in 37.5% phosphoric acid for 2 minutes and wiped
      by CPP-ACP for 3 minutes, then immersed in distilled water for 7 days),
      experimental group B (immersed in 37.5% Phosphoric acid for 2 minutes and wiped
      by CPP-ACP for 3 minutes, then immersed in distilled water for 14 days),
      experimental group C (immersed in 37.5% phosphoric acid for 2 minutes and wiped
      by CPP-ACP for 3 minutes, then immersed in distilled water for 21 days),
      experimental group D (immersed in 37.5% phosphoric acid for 2 minutes and wiped
      by CPP-ACP for 3 minutes, then immersed in distilled water for 28 days), with 6
      slabs in each group. The mineral content was determined by scanning electron
      microscope. RESULTS: There was a large amount of mineral deposited on enamel
      surface in experimental group A, B, C, D. The calcium content of experimental
      group D was higher than those of other 3 experimental groups. The calcium content
      of experimental group A, B, C, D (66.53 +/- 0.63, 67.00 +/- 0.49, 67.07 +/- 0.24,
      67.18 +/- 0.50) was higher than that of acid etching group (65.74 +/- 0.68) (P <
      0.05). There was no significant difference of the calcium content among
      experimental group A, B, C, D (P > 0.05). CONCLUSIONS: CPP-ACP can reduce enamel
      demineralization and promote remineralization in vitro.

PMID- 23534520
TI  - [Influence of the diameter and length of the mini-implant on the primary
      stability after loading with composite forces].
AB  - OBJECTIVE: To investigate the influence of the diameter and length of the mini
      implant on the primary stability after loading with composite forces (CF) which
      contained torque and horizontal forces (HF). METHODS: Ninety-six finite element
      models were established by the combination of mini-implant and bone, diameters
      (1.2 mm, 1.6 mm, 2.0 mm) and length (6 mm, 8 mm, 10 mm, 12 mm). There were 12
      sizes, each size corresponded with 8 models. Group HF (each size n = 4) was
      loaded with 1.96 N horizontal force and Group CF (each size n = 4) was loaded
      with composite force which contained 6 N.mm torque and 1.96 N horizontal force.
      The maximum displacement of mini-implant with different force directions, implant
      diameters and lengths were evaluated. RESULTS: The effect of force direction on
      the displacement related to diameter of mini-implant. The maximum displacement
      under load with HF respectively was changed with the changing of diameter[1.2 mm:
      (7.71 +/- 0.49) um; 1.6 mm: (3.94 +/- 0.31) um; 2.0 mm: (2.32 +/- 0.43) um],
      which were smaller than the maximum displacement of Group CF [1.2 mm: (9.22 +/-
      0.63) um; 1.6 mm: (4.62 +/- 0.52) um; 2.0 mm: (2.69 +/- 0.49) um] (P < 0.05).
      When diameter was 1.2 mm, the difference of the maximum displacement [(1.61 +/-
      0.22) um] between Group HF and CF was more obvious than that when the diameter
      was 1.6 mm or 2.0 mm [(0.64 +/- 0.12), (0.49 +/- 0.06) um] (P < 0.05).
      CONCLUSIONS: The composite force had unfavorable effect on the primary stability
      of the mini-implant. The diameter of the mini-implant had better be larger than
      1.2 mm when the composite forces were applied.

PMID- 23534521
TI  - [Effect of processing time on the surface properties of titanium micro-arc
      oxidation film].
AB  - OBJECTIVE: To explore the effect of changes of processing time on the surface
      properties of titanium coating formed by micro-arc oxidation (MAO). METHODS:
      Forty-four disc-shaped pure titanium specimens with 10 mm diameter and 1 mm
      thickness were equally divided into 4 groups and processed by MAO technique in
      electrolytes containing 0.2 mol/L calcium acetate (CA) and 0.02 mol/L beta
      glycerol phosphate disodium salt pentahydrate (beta-GP). The processing time were
      set at 1 min, 5 min, 10 min and 15 min respectively. The topograph of the MAO
      film surface and the film-substrate interface was observed by a scanning electron
      microscopy (SEM), and the composition was analyzed by an energy dispersive
      spectroscope (EDS) incorporated in the SEM. The phase and the microstructure of
      the film were analyzed by X-ray diffraction (XRD). The roughness of the film was
      measured using a roughness tester. The surface static contact angle was detected
      by a contact angle measurement instrument and the surface energy was calculated
      accordingly. RESULTS: With the increase of processing time from 1 min to 15 min,
      the pore size increased from (1.30 +/- 0.07) um to (1.55 +/- 0.09) um, and film
      thickness increased from (10.2 +/- 1.1) um to (20.9 +/- 2.9) um. The content of
      the Ca in the film increased accordingly, and Ca/P increased from 1.99 to 2.45,
      and the surface energy increased from 24.62 mJ/m(2) to 39.49 mJ/m(2). Meanwhile,
      the XRD pattern indicated that rutile increased but anatase and titanium
      decreased gradually. At the time of 15 min, part of the MAO film peeled off.
      CONCLUSIONS: Processing time has impact on the thickness, surface topography,
      crystal component and surface energy of titanium MAO coating. MAO film treated
      for 5 - 10 min demonstrated favorable surface properties.

PMID- 23534522
TI  - [Effect of curing modes on knoop hardness and microtensile bond strength of two
      dentin adhesives].
AB  - OBJECTIVE: To evaluated the effect of curing modes and light-cure times on knoop
      hardness (KH) and microtensile bond strength (uTBS) of dentin adhesives in vitro.
      METHODS: Twenty molars were made into 80 dentin slices (about 1 mm thick). The
      dentin slices were prepared with an etch&rinse adhesive A (ONE-STEP PLUS) and a
      self-etch adhesive B (Clearfil SE Bond), and light-cured respectively under fast
      mode, i.e.1250 mW/cm(2) light intensity for 10 s, 15 s, 20 s, and ramp mode (soft
      start curing mode), i.e.initial 0 mW/cm(2) gradually increasing to 1250 mW/cm(2)
      in first 10 s, then steady for the next 10 s. The prepared dentin slices were
      kept in dark dry room for 24 h at 37 degrees C, and KH were tested. The other 40
      molars were flattened to expose coronal dentin, prepared with adhesives as above.
      Then the prepared teeth were restored with resin composites incrementally and
      cured under fast mode. The restored teeth were stored in water for 24 h at 37
      degrees C, and slowly sectioned to obtain multiple bonded beams. After 7 d water
      storage, the samples received microtensile bond test, and the failure models of
      beams were observed under a stereomicroscope. Data were analyzed by ANOVA and LSD
      test (alpha = 0.05). RESULTS: No statistical difference in KH [(28.20 +/- 5.36),
      (29.13 +/- 5.60), (28.13 +/- 4.40), (27.06 +/- 3.77) MPa] and uTBS [(22.30 +/-
      5.07), (22.73 +/- 6.59), (26.32 +/- 6.17), (25.67 +/- 4.31) MPa] of adhesive A
      were found between four curing conditions (fast mode for 10 s, 15 s, 20 s and
      ramp mode for 20 s) (P > 0.05). In adhesive B, KH of Fast 20 s [(28.23 +/- 3.67)
      MPa] were significantly higher than those of Fast 10 s [(14.15 +/- 2.24) MPa] and
      Fast 15 s [(17.63 +/- 2.17) MPa] (P < 0.05). The uTBS of Fast 20 s [(42.52 +/-
      3.59) MPa] were significantly higher than those of Fast 10 s [(24.21 +/- 3.60)
      MPa], Fast 15 s [(22.25 +/- 4.16) MPa] and Ramp 20 s [(31.12 +/- 5.40) MPa] (P <
      0.05). In Fast 20 s and Ramp 20 s modes, there were no statistical difference in
      KH of adhesive A and B, while uTBS of adhesive B were higher than that of
      adhesive A(P < 0.05). CONCLUSIONS: As for different type dentin adhesives, the
      appropriate curing time in fast mode is different, and ramp mode (soft start
      curing mode) has no advantage over fast mode.

PMID- 23534523
TI  - [The masseter inhibitory reflex and the recovery of the reflex after magnetic
      stimulation in normal subjects].
AB  - OBJECTIVE: To analyze the masseter inhibitory reflex (MIR) and the recovery cycle
      of the MIR reflex after magnetic stimulation in normal subjects. METHODS: In 30
      healthy subjects we studied the MIR evoked by single magnetic stimulation in the
      mental territory. Masseter electromyographic activity, latency and duration of
      the early silent periods (SP1) and late silent periods (SP2), and SP2 amplitude
      percent were recorded. Paired stimuli technique was used, conditioning and test
      stimuli were delivered at different interstimulus intervals (ISI), ie.100, 200,
      300, 400, 500, and 600 ms, then the recovery cycle of the MIR was analyzed.
      RESULTS: Latency of SP1 was 12.1 (11.1, 14.4) ms, and duration of the SP1 was
      (17.3 +/- 2.9) ms. Latency of SP2 was (47.7 +/- 6.0) ms, and duration of the SP2
      was (39.7 +/- 13.3) ms. SP2 amplitude percent was 100.0%. With the paired stimuli
      technique, SP1 of the inhibitory reflex evoked by the test stimuli was found to
      be stable at every ISIs, but SP2 of the inhibitory reflex evoked by the test
      stimuli, instead, varied according to different ISI. With the short ISI, the area
      of SP2 evoked by the test stimuli was reduced, and with the increase of the ISI,
      the recovery degree of the area of SP2 evoked by the test stimuli was ascending,
      at 100 ms the SP2 amplitude percent was 17.1%, at 400 ms it was 93.4%, and it was
      close to 100% at 600 ms. CONCLUSIONS: The study indicates that the use of the MIR
      elicited by the single and paired magnetic stimulation may be useful to examine
      or quantify some craniofacial diseases.

PMID- 23534524
TI  - [Effect of experimental occlusal hypofunction on the three-dimensional
      microarchitecture of mandibular bone in rats].
AB  - OBJECTIVE: To investigate the effects of experimental occlusal hypofunction on
      the architecture of rat's mandibular bone. METHODS: Forty Sprague-Dawley (SD)
      male rats were randomly divided into experimental occlusal hypofunction group and
      control group, with 20 rats in each group. Experimental occlusal hypofunction
      group rats were fitted with a metal cap to the maxillary and mandibular incisor,
      to eliminate the occlusal forces on rat molars. In control group, a metal ring
      was fitted to the maxillary and mandibular incisor to maintain molar occlusal
      contact. Then the rats were killed under deep anaesthesia at 0 week and at the
      end of 2, 4, 6, and 8 weeks, and the mandibles were immediately removed for
      measurement of the three-dimensional architecture of cancellous bone in the
      alveolar process with micro-CT. RESULTS: At the end of week 4, the bone
      volume/total volume (BV/TV) in the hypofunction group decreased compared with the
      control group [control group:(0.65 +/- 0.05)%, experimental group: (0.60 +/-
      0.05)%, P < 0.05] and lasted until the end of the experiment [control group:
      (0.72 +/- 0.06)%, experimental group: (0.51 +/- 0.07)%, P < 0.01]. The similar
      result was also observed in trabecula thickness (Tb. Th) in experimental animals
      [control group: (168 +/- 15), (170 +/- 25), (180 +/- 18) um, experimental group:
      (152 +/- 20), (145 +/- 19), (142 +/- 15) um, P < 0.05]. The trabecula spacing
      (Tb. Sp) in the hypofunction group increased from the end of week 4 to the end of
      week 8 compared with the matched control groups [control group: (264 +/- 21),
      (284 +/- 17), (282 +/- 26) um, experimental group: (306 +/- 30), (316 +/- 18),
      (332 +/- 18) um, P < 0.05]. The trabecula number (Tb.N) of experimental animals
      decreased from the end of week 6[control group:(3.59 +/- 0.22) mm(-1),
      experimental group: (3.03 +/- 0.31) mm(-1), P < 0.05] to the end of week
      8[control group: (3.66 +/- 0.24) mm(-1), experimental group: (2.85 +/- 0.18) mm(
      1), P < 0.01]. CONCLUSIONS: Experimental occlusal hypofunction can result in the
      change of mandibular alveolar process three-dimensional architecture.

PMID- 23534525
TI  - [Ablation of enamel and dentin with computerized numerical controlled femtosecond
      pulsed laser: a primary study on the ablation rate].

PMID- 23534526
TI  - [International caries detection and assessment system (ICDAS) in the application
      stomatology].

PMID- 23534527
TI  - Preparedness for and impact of tropical cyclone Yasi in North Queensland,
      Australia.
AB  - INTRODUCTION: Tropical cyclone (TC) Yasi, thought to be the largest and most
      severe cyclone to cross the Queensland coast since 1918, made landfall on the
      southern tropical coast near Mission Beach and continued to track westward across
      Northern Queensland on February 3, 2011. The warning and response model (WRM)
      suggests that situational factors, personal characteristics, and social
      contextual variables influence the degree of threat perceived and protective
      actions taken. Aim The aim of this study was to examine preparation for this
      impending natural disaster by residents of the affected regions, and to identify
      the residents' resource losses and symptoms of psychological distress following
      TC Yasi. METHODS: A cross-sectional survey was conducted 6-12 months after the
      cyclone using an adapted tool designed to measure preparedness, loss and
      psychosocial distress. Four hundred and thirty-three responses were received.
      Statistical analysis was conducted using Statistical Package for the Social
      Sciences (SPSS). Categorical characteristics were described using sample size and
      percentages. RESULTS: Almost all respondents perceived the cyclone warning as
      serious or very serious, and more than a third started preparing for the cyclone
      at least three days before it reached landfall. Overall, 115 (26.7%) respondents
      reported moderate and 59 (13.7%) reported major property damage; 72 (17.1%)
      reported a moderate and 49 (11.6%) reported a major change in their feeling of
      whether they have control over their life; 55 (13.1%) reported a major change in
      their motivation of getting things done; and 33 (7.9%) reported a major change in
      their perception of feeling valuable to others. Overall, 142 (34.1%) documented
      at least one of five symptoms of acute distress. CONCLUSION: The findings
      document the experiences of Australians who have lived through tropical cyclone
      Yasi. The results support the WRM theory which proposes that people with previous
      experience take threatened disasters seriously.

PMID- 23534528
TI  - Hyperconjugative interactions in permethylated siloxanes and ethers: the nature
      of the SiO bond.
AB  - The paradoxically low basicity (despite high anionicity) of oxygen in the
      characteristic Si-O-Si linkages of silicone polymers is investigated with hybrid
      density functional and natural bond orbital (NBO) computational methods,
      extending a previous study of idealized disiloxane and dimethyl ether parent
      species to fully methylated derivatives that more faithfully model the silicone
      polymers of industrial and environmental importance. Despite the complicating
      distortions of the sterically crowded di-t-butyl ether "analog", the physical
      picture of enhanced hyperconjugative (resonance-type) delocalization in Si-O vs C
      O bonding is essentially preserved (and indeed accentuated) in permethylated
      species. NBO-based orbital overlap diagrams are employed in conjunction with
      structural, hybridization, and polarity descriptors to illustrate the subtle
      phase-matching relationships that confer superior enthalpic and entropic
      stability (and low basicity) on permethylated Si-O-Si linkages. Our results
      challenge both ionic models of Si-O bonding and conventional electrostatic-type
      models of H-bonding and acid-base reactivity.

PMID- 23534529
TI  - Effect of nonsurgical periodontal treatment on C-reactive protein levels in
      maintenance hemodialysis patients.
AB  - OBJECTIVE: C-reactive protein (CRP) has been implicated as a possible mediator of
      the association between periodontitis and several systemic diseases. This study
      evaluated the impact of nonsurgical periodontal treatment on the serum levels of
      CRP in chronic kidney disease (CKD) patients on hemodialysis. METHODS: A total of
      77 CKD patients on hemodialysis were included in this study. At baseline,
      periodontal examination was assessed for all the patients, and chronic
      periodontitis was defined through clinical attachment level and probing pocket
      depth, according to the American Association of Periodontology. Nonsurgical
      periodontal treatment was performed and serum levels of CRP were evaluated at
      baseline and 8 weeks after periodontal treatment. RESULTS: Periodontal treatment
      resulted in significant reductions in CRP levels (p < 0.001). The difference
      between pre- and posttreatment CRP concentrations did not show any significant
      relationship with the severity of periodontitis. CONCLUSIONS: Periodontitis is an
      important source of systemic inflammation in CKD patients. Nonsurgical
      periodontal treatment can effectively reduce the serum level of CRP in these
      patients.

PMID- 23534530
TI  - Pickering-emulsion-polymerized polystyrene/Fe2O3 composite particles and their
      magnetoresponsive characteristics.
AB  - Core-shell-structured magnetic polystyrene (PS)/inorganic particles were
      fabricated by Pickering emulsion polymerization using nanosized Fe2O3 particles
      as a solid stabilizer. Scanning electron microscopy and transmission electron
      microscopy confirmed the synthesized PS/Fe2O3 particles to be comprised of a PS
      surface coated with Fe2O3 nanoparticles. The chemical structure of the composite
      nanospheres was characterized by Fourier transform infrared spectroscopy and X
      ray diffraction. The thermal properties of composite nanospheres and
      corresponding pure polymer were examined by thermogravimetric analysis. The
      rheological properties of the core-shell-structured magnetic PS/inorganic
      particles dispersed in silicone oil were investigated under an external magnetic
      field strength using a rotational rheometer. The particles with extremely lower
      density than common magnetic particles exhibited solid-like magnetorheological
      phase characteristics, and the flow curves were fitted to the Cho-Choi-Jhon model
      of the rheological equation of state.

PMID- 23534531
TI  - Ultrafast time-resolved pump-probe spectroscopy of PYP by a sub-8 fs pulse laser
      at 400 nm.
AB  - Impulsive excitation of molecular vibration is known to induce wave packets in
      both the ground state and excited state. Here, the ultrafast dynamics of PYP was
      studied by pump-probe spectroscopy using a sub-8 fs pulse laser at 400 nm. The
      broadband spectrum of the UV pulse allowed us to detect the pump-probe signal
      covering 360-440 nm. The dependence of the vibrational phase of the vibrational
      mode around 1155 cm(-1) on the probe photon energy was observed for the first
      time to our knowledge. The vibrational mode coupled to the electronic transition
      observed in the probe spectral ranges of 2.95-3.05 and 3.15-3.35 eV was
      attributed to the wave packets in the ground state and the excited state,
      respectively. The frequencies in the ground state and excited state were
      determined to be 1155 +/- 1 and 1149 +/- 1 cm(-1), respectively. The frequency
      difference is due to change after photoexcitation. This means a reduction of the
      bond strength associated with pi-pi* excitation, which is related to the
      molecular structure change associated with the primary isomerization process in
      the photocycle in PYP. Real-time vibrational modes at low frequency around 138,
      179, 203, 260, and 317 cm(-1) were also observed and compared with the Raman
      spectrum for the assignment of the vibrational wave packet.

PMID- 23534533
TI  - Immunotherapy for targeting tau pathology in Alzheimer's disease and tauopathies.
AB  - The drawbacks of amyloid immunotherapy, including the development of
      encephalitis, the lack of clinical improvement and of any effect on
      neurofibrillary tangles (NFTs), coupled with the central role of NFTs in
      dementia, may point that clearance of amyloid pathology is not sufficient for
      improving the dementia symptoms in Alzheimer's disease (AD) patients. This
      further supported the concept that immunotherapy targeting the NFT proteinous
      aggregates may be preferential. Yet, the encephalitogenicity of full-length tau
      protein under a proinflammatory CNS milieu, reported by us in immunized mice,
      demands to carefully and selectively target pathological tau, while not the
      normal functional tau, and assuring both efficacy (anti-NFT effect) as well as
      safety (free of encephalitis) of a potential vaccine. Accumulating evidence from
      animal studies shows that tau-immunotherapy, targeting selectively pathological
      tau, particularly the phosphorylated-tau isoforms, reduces the tau-pathology and
      improves the symptoms of dementia. These findings are based on studies from
      different research groups, including our laboratory, conducted in different
      animal models and using various immunization protocols. There is also evidence
      that the decrease in NFTs is antibody-mediated involving the endosomal/ lysosomal
      pathway. No adverse effects were reported by the research groups, including also
      our study in which mice were immunized with a single injection of phosphorylated
      tau peptide under a CNS proinflammatory milieu. In this review, I discuss the
      studies reported in this field, focusing on different approaches, different
      immunization protocols and mechanistic aspects, with a focus on the promising
      efficacy of the tau-immunotherapy, while addressing the safety issues already in
      the preclinical stage, before progressing to clinical trials.

PMID- 23534532
TI  - Factor VIII genotype characterization of haemophilia A affected patients with
      transient and permanent inhibitors: a comprehensive Argentine study of inhibitor
      risks.
AB  - Inhibitor development against exogenous factor VIII is a severe impairment of
      replacement therapy affecting 18% of Argentine patients with severe haemophilia A
      (HA). To study the molecular predisposition for inhibitor development, we
      genotyped 260 HA patients with and without inhibitors, countrywide. The inhibitor
      positive population (19 transients, 15 low responders, LR and 70 high responders,
      HR) of 104 severe-HA patients showed 59 Inv22 (intron 22 inversions), 18 small
      ins/del-frameshifts, 12 gross deletions, 12 nonsense, one splicing defect and two
      missense, p.Arg531Pro and p.Leu575Pro, both LR and thought to impair FVIII A2
      domain secondary structure. In addition, a patient with mild HA and HR showed the
      missense p.Glu1704Lys associated with two neutral intronic substitutions
      potentially affecting the A3 domain. A case/control study (84/143) permitted
      estimation of F8 genotype-specific inhibitor risks [OR; prevalence (CI)] in
      severe-HA patients classifying a high-risk group including multi-exon deletions
      [3.66; 55% (19-100)], Inv22 [1.8; 24% (19-100)] and nonsense in FVIII-LCh [1.2;
      21% (7-59)]; an average risk group including single-exon deletions, indel
      frameshifts and nonsense-HCh; and a low-risk group represented by missense
      defects [0.14; 3% (0.6-11)]. Analysis of inhibitor concordance/discordance in
      related patients indicated additional genetic factors other than F8 genotype for
      inhibitor formation. No significant inhibitor-predisposing factors related to
      FVIII product exposure were found in age- and F8 genotype-stratified populations
      of severe-HA patients. In conclusion, the Argentine HA patient series presents
      similar global and mutation-specific inhibitor risks than the HA database and
      other published series. This case-specific information will help in designing
      fitted therapies and follow-up protocols in Argentina.

PMID- 23534534
TI  - Actions of the anti-angiogenic compound angiostatin in an animal model of
      Alzheimer's disease.
AB  - We have examined the anti-angiogenic compound, angiostatin as a modulator of
      inflammatory reactivity and vascular responses and for neuroprotection in an
      animal model of Alzheimer's disease (AD). Intra-hippocampal amyloidbeta (Abeta1
      42) injection, relative to controls phosphate buffer saline (PBS) or reverse
      peptide Abeta42-1, increased gliosis in the molecular layer (ML) of rat
      hippocampus. Vascular remodeling was indicated from increased microvessel
      immunoreactivity (ir) in ML suggesting the possibility of an angiogenic response
      to peptide injection. Administration of Abeta1-42 also induced a loss of neurons
      in the granule cell region of hippocampus relative to controls. Treatment of
      peptide-injected rats with angiostatin was associated with a spectrum of
      modulatory effects including reduced microgliosis (by 34%), diminished
      microvessel ir (by 36%) and increased neuronal viability (by 31%) compared with
      peptide injection alone. Angiostatin treatment was ineffective in reducing
      astrogliosis induced by Abeta1-42 and applied alone the compound had no
      significant effect to alter gliosis, microvessel ir or neuronal viability
      compared with PBS control. In vitro, angiostatin significantly attenuated
      secretion of the pro-angiogenic agent, vascular endothelial growth factor (VEGF)
      in lipopolysaccharide (LPS)-stimulated THP-1 cells. Our findings provide novel
      evidence for a broad spectrum of angiostatin effects in an animal model of AD
      including actions to reduce inflammatory reactivity, stabilize vascular
      remodeling and confer neuroprotection. The overall effects of angiostatin are
      consistent with actions of the compound to inhibit microglial secretion of VEGF.

PMID- 23534535
TI  - Parasitosis of Metabronema sp. (Nematoda: Cystidicolidae) in Caribbean
      porcupinefish, Diodon hystrix (L.).

PMID- 23534536
TI  - A label-free potentiometric sensor principle for the detection of antibody
      antigen interactions.
AB  - We report here on a new potentiometric biosensing principle for the detection of
      antibody-antigen interactions at the sensing membrane surface without the need to
      add a label or a reporter ion to the sample solution. This is accomplished by
      establishing a steady-state outward flux of a marker ion from the membrane into
      the contacting solution. The immunobinding event at the sensing surface retards
      the marker ion, which results in its accumulation at the membrane surface and
      hence in a potential response. The ion-selective membranes were surface-modified
      with an antibody against respiratory syncytial virus using click chemistry
      between biotin molecules functionalized with a triple bond and an azide group on
      the modified poly (vinyl chloride) group of the membrane. The bioassay sensor was
      then built up with streptavidin and subsequent biotinylated antibody. A
      quaternary ammonium ion served as the marker ion. The observed potential was
      found to be modulated by the presence of respiratory syncytial virus bound on the
      membrane surface. The sensing architecture was confirmed with quartz crystal
      microbalance studies, and stir effects confirmed the kinetic nature of the marker
      release from the membrane. The sensitivity of the model sensor was compared to
      that of a commercially available point-of-care test, with promising results.

PMID- 23534539
TI  - Unidirectional charge transfer in di-cobalt valence tautomeric compound finely
      tuned by ancillary ligand.
AB  - A dinuclear valence tautomeric compound containing a cationic structure with
      crystallographically distinguishable hs-Co(II) and ls-Co(III) centers undergoes
      unidirectional charge transfer.

PMID- 23534537
TI  - Marital conflict, allostatic load, and the development of children's fluid
      cognitive performance.
AB  - Relations between marital conflict, children's respiratory sinus arrhythmia
      (RSA), and fluid cognitive performance were examined over 3 years to assess
      allostatic processes. Participants were 251 children reporting on marital
      conflict, baseline RSA, and RSA reactivity (RSA-R) to a lab challenge were
      recorded, and fluid cognitive performance was measured using the Woodcock-Johnson
      III. A cross-lagged model showed that higher levels of marital conflict at age 8
      predicted weaker RSA-R at age 9 for children with lower baseline RSA. A growth
      model showed that lower baseline RSA in conjunction with weaker RSA-R predicted
      the slowest development of fluid cognitive performance. Findings suggest that
      stress may affect development of physiological systems regulating attention,
      which are tied to the development of fluid cognitive performance.

PMID- 23534540
TI  - Abstracts of the 24th Biennial Meeting of the International Society for
      Neurochemistry and the American Society for Neurochemistry. April 20-24, 2013.
      Cancun, Mexico.

PMID- 23534541
TI  - Rapid cytoskeleton remodelling in dendritic cells following invasion by
      Toxoplasma gondii coincides with the onset of a hypermigratory phenotype.
AB  - Host cell manipulation is an important feature of the obligate intracellular
      parasite Toxoplasma gondii. Recent reports have shown that the tachyzoite stages
      subvert dendritic cells (DC) as a conduit for dissemination (Trojan horse) during
      acute infection. To examine the cellular basis of these processes, we performed a
      detailed analysis of the early events following tachyzoite invasion of human
      monocyte-derived DC. We demonstrate that within minutes after tachyzoite
      penetration, profound morphological changes take place in DC that coincide with a
      migratory activation. Active parasite invasion of DC led to cytoskeletal actin
      redistribution with loss of adhesive podosome structures and redistribution of
      integrins (CD18 and CD11c), that concurred with the onset of DC hypermotility in
      vitro. Inhibition of parasite rhoptry secretion and invasion, but not inhibition
      of parasite or host cell protein synthesis, abrogated the onset of morphological
      changes and hypermotility in DC dose-dependently. Also, infected DC, but not by
      stander DC, exhibited upregulation of C-C chemokine receptor 7 (CCR7). Yet, the
      onset of parasite-induced DC hypermotility preceded chemotactic migratory
      responsesin vitro. Collectively, present data reveal that invasion of DC by T.
      gondii initiates a series of regulated events, including rapid cytoskeleton
      rearrangements, hypermotility and chemotaxis, that promote the migratory
      activation of DC. 

PMID- 23534542
TI  - Treatment of HCV infection by targeting microRNA.
AB  - BACKGROUND: The stability and propagation of hepatitis C virus (HCV) is dependent
      on a functional interaction between the HCV genome and liver-expressed microRNA
      122 (miR-122). Miravirsen is a locked nucleic acid-modified DNA phosphorothioate
      antisense oligonucleotide that sequesters mature miR-122 in a highly stable
      heteroduplex, thereby inhibiting its function. METHODS: In this phase 2a study at
      seven international sites, we evaluated the safety and efficacy of miravirsen in
      36 patients with chronic HCV genotype 1 infection. The patients were randomly
      assigned to receive five weekly subcutaneous injections of miravirsen at doses of
      3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period.
      They were followed until 18 weeks after randomization. RESULTS: Miravirsen
      resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the
      end of active therapy. In the miravirsen groups, the mean maximum reduction in
      HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=0.01) for
      patients receiving 3 mg per kilogram, 2.9 (P=0.003) for those receiving 5 mg per
      kilogram, and 3.0 (P=0.002) for those receiving 7 mg per kilogram, as compared
      with a reduction of 0.4 in the placebo group. During 14 weeks of follow-up after
      treatment, HCV RNA was not detected in one patient in the 5-mg group and in four
      patients in the 7-mg group. We observed no dose-limiting adverse events and no
      escape mutations in the miR-122 binding sites of the HCV genome. CONCLUSIONS: The
      use of miravirsen in patients with chronic HCV genotype 1 infection showed
      prolonged dose-dependent reductions in HCV RNA levels without evidence of viral
      resistance. (Funded by Santaris Pharma; ClinicalTrials.gov number, NCT01200420.).

PMID- 23534544
TI  - The ethics of not hiring smokers.

PMID- 23534543
TI  - Rhinovirus wheezing illness and genetic risk of childhood-onset asthma.
AB  - BACKGROUND: Both genetic variation at the 17q21 locus and virus-induced
      respiratory wheezing illnesses are associated with the development of asthma. Our
      aim was to determine the effects of these two factors on the risk of asthma in
      the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on
      Asthma in Childhood (COPSAC) birth cohorts. METHODS: We tested genotypes at the
      17q21 locus for associations with asthma and with human rhinovirus (HRV) and
      respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions
      between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the
      risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes
      in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs).
      RESULTS: The 17q21 variants were associated with HRV wheezing illnesses in early
      life, but not with RSV wheezing illnesses. The associations of 17q21 variants
      with asthma were restricted to children who had had HRV wheezing illnesses,
      resulting in a significant interaction effect with respect to the risk of asthma.
      Moreover, the expression levels of ORMDL3 and of GSDMB were significantly
      increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The
      expression of these genes was associated with 17q21 variants in both conditions,
      although the increase with exposure to HRV was not genotype-specific.
      CONCLUSIONS: Variants at the 17q21 locus were associated with asthma in children
      who had had HRV wheezing illnesses and with expression of two genes at this
      locus. The expression levels of both genes increased in response to HRV
      stimulation, although the relative increase was not associated with the 17q21
      genotypes. (Funded by the National Institutes of Health.).

PMID- 23534545
TI  - Micromanaging hepatitis C virus.

PMID- 23534546
TI  - Phasing out fee-for-service payment.

PMID- 23534547
TI  - Conflicts and compromises in not hiring smokers.

PMID- 23534548
TI  - Preventing type 2 diabetes after gestational diabetes: women's experiences and
      implications for diabetes prevention interventions.
AB  - AIMS: To explore factors influencing post-natal health behaviours following the
      experience of gestational diabetes, and to elicit women's views about the
      feasibility of lifestyle intervention to prevent diabetes during the first 2
      years after childbirth. METHODS: Qualitative study using semi-structured
      interviews with women who had gestational diabetes. In phase 1 (31 women),
      interviews explored the experience of gestational diabetes, ideas about future
      risk of diabetes and factors influencing post-natal health-related behaviours.
      Statements were developed summarizing women's views of lifestyle change to
      prevent diabetes. In phase 2 (14 women), interviews explored how the passage of
      time had contributed to changes in health behaviour, and the statements were used
      to develop views about diabetes interventions. RESULTS: Women were aware of their
      risk of developing diabetes, but did not always act on such knowledge. Pregnancy
      motivated behaviour changes to benefit the unborn child, but after delivery these
      changes were often not maintained. Tiredness, maternal attachment and childcare
      demands were prominent barriers in the early post-natal months. Later, work,
      family and child development became more significant barriers. Many women became
      more receptive to healthy eating messages around the time of weaning. Women were
      positive about long-term support for self-management to reduce their diabetes
      risk. CONCLUSIONS: There is potential to reduce the risk of Type 2 diabetes post
      natally among women with gestational diabetes. Interventions need to be developed
      that take into account contextual factors and competing demands, are flexible and
      respond to women's individual circumstances. Randomized trials of such
      interventions are warranted.

PMID- 23534549
TI  - Retinal toxicity associated with high dose of meclofenamic acid.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used medications because
      they provide effective relief of chronic pain and inflammation through inhibition
      of cyclooxygenase (COX). However, visual side effects also have been reported,
      such as temporary blindness, visual field defect, blurred vision, scotomata, and
      color vision changes subsequent to short- or long-term use. Our aim was to
      investigate the effect of a high dose of meclofenamic acid (MFA) on the retina.
      In our study, we applied electroretinography (ERG) and histologic examination to
      study functional and morphological damage of the retina in rabbits after MFA
      treatment. We reveal that MFA markedly decreased the amplitudes of b-wave of Rod
      response and a- and b-wave of the scotopic standard combined ERG, respectively,
      and induced morphological destruction of the retina, especially photoreceptor
      cells. We conclude that a high dose of MFA causes retinal toxicity and impairs
      visual transduction. These findings may explain, at least partially, the vision
      problems of certain clinically used NSAIDs.

PMID- 23534550
TI  - Thyroid involvement by laryngeal cancer among Iranian patients.
AB  - OBJECTIVE: Asian patients with laryngeal cancer have been reported to have a high
      prevalence of thyroid involvement. This study aimed to investigate the prevalence
      of thyroid invasion in Iranian patients with laryngeal cancer. METHODS: Hospital
      records for all patients with a definite diagnosis of laryngeal cancer between
      1996 and 2009 (351 patients) were reviewed, and the prevalence of thyroid
      invasion was established based on the pathology report at the time of surgery.
      RESULTS: Thyroid invasion was found in 16 patients (4.55 percent), and was
      limited to one thyroid lobe in two-thirds of cases. All instances of thyroid
      invasion occurred in patients with stage III (81.25 percent) or IV (18.75
      percent) cancer. No case of metastasis was reported. The glottic region was
      identified as the tumour origin in most cases of thyroid invasion (56.25
      percent). CONCLUSION: Most cases of thyroid invasion by laryngeal cancer occurred
      in cancer stage III, at grades G1 and G2, among male patients, and arose from
      tumours of the glottic region.

PMID- 23534551
TI  - A double-leg donor-acceptor molecular elevator: new insight into controlling the
      distance of two platforms.
AB  - A double-leg elevator with an electron-rich anthracene moiety at the platformlike
      component and an electron-deficient naphthalenediimide unit in the middle of a
      double-leg riglike component was prepared through "click chemistry", in which the
      reversible elevator movement between different levels could be controlled upon
      the addition of base and acid.

PMID- 23534552
TI  - Launching spiking ligands into a protein-protein interface: a promising strategy
      to destabilize and break interface formation in a tRNA modifying enzyme.
AB  - Apart from competitive active-site inhibition of protein function, perturbance of
      protein-protein interactions by small molecules in oligodomain enzymes opens new
      perspectives for innovative therapeutics. tRNA-guanine transglycosylase (TGT), a
      potential target to treat shigellosis, is active only as the homodimer.
      Consequently, disruption of the dimer interface by small molecules provides a
      novel inhibition mode. A special feature of this enzyme is the short distance
      between active site and rim of the dimer interface. This suggests design of
      expanded active-site inhibitors decorated with rigid, needle-type substituents to
      spike into potential hot spots of the interaction interface. Ligands with
      attached ethinyl-type substituents have been synthesized and characterized by Kd
      measurements, crystallography, noncovalent mass spectrometry, and computer
      simulations. In contrast to previously determined crystal structures with
      nonextended active-site inhibitors, a well-defined loop-helix motif, involved in
      several contacts across the dimer interface, falls apart and suggests enhanced
      flexibility once the spiking ligands are bound. Mass spectrometry indicates
      significant destabilization but not full disruption of the complexed TGT
      homodimer in solution. As directed interactions of the loop-helix motif obviously
      do not determine dimer stability, a structurally conserved hydrophobic patch
      composed of several aromatic amino acids is suggested as interaction hot spot.
      The residues of this patch reside on a structurally highly conserved helix-turn
      helix motif, which remains unaffected by the bound spiking ligands. Nevertheless,
      it is shielded from solvent access by the loop-helix motif that becomes perturbed
      upon binding of the spiking ligands, which serves as a possible explanation for
      reduced interface stability. 

PMID- 23534553
TI  - Engineering the microstructure of electrospun fibrous scaffolds by
      microtopography.
AB  - Controlling the structure and organization of electrospun fibers is desirable for
      fabricating scaffolds and materials with defined microstructures. However, the
      effects of microtopography on the deposition and, in turn, the organization of
      the electrospun fibers are not well understood. In this study, conductive
      polydimethylsiloxane (PDMS) templates with different micropatterns were
      fabricated by combining photolithography, silicon wet etching, and PDMS molding
      techniques. The fiber organization was varied by fine-tuning the microtopography
      of the electrospinning collector. Fiber conformity and alignment were influenced
      by the depth and the slope of microtopography features, resulting in scaffolds
      comprising either an array of microdomains with different porosity and fiber
      alignment or an array of microwells. Microtopography affected the fiber
      organization for hundreds of micrometers below the scaffold surface, resulting in
      scaffolds with distinct surface properties on each side. In addition, the fiber
      diameter was also affected by the fiber conformity. The effects of the fiber
      arrangement in the scaffolds on the morphology, migration, and infiltration of
      cells were examined by in vitro and in vivo experiments. Cell morphology and
      organization were guided by the fibers in the microdomains, and cell migration
      was enhanced by the aligned fibers and the three-dimensional scaffold structure.
      Cell infiltration was correlated with the microdomain porosity. Microscale
      control of the fiber organization and the porosity at the surface and through the
      thickness of the fibrous scaffolds, as demonstrated by the results of this study,
      provides a powerful means of engineering the three-dimensional structure of
      electrospun fibrous scaffolds for cell and tissue engineering.

PMID- 23534554
TI  - Nurse aide decision making in nursing homes: factors affecting empowerment.
AB  - AIMS AND OBJECTIVES: To evaluate factors affecting structural empowerment among
      nurse aides in nursing homes. BACKGROUND: Structural empowerment can be defined
      as the actual rather than perceived ability to make autonomous decisions within
      an organisation. Given the paucity of research on the subject, this study helps
      to close the gap by identifying factors that affect nurse aide empowerment, that
      is, decision-making among nurse aides. METHODS: The data for the study come from
      self-administered questionnaires distributed to direct-care workers (nurse aides)
      in 11 nursing homes in a southern state in the USA. Ordinary least square
      regression models were estimated to analyse the effects of demographic
      predictors, personal factors (competency, emotional exhaustion and positive
      attitude) and structural characteristics (coworker and supervisor support,
      information availability and shared governance) on nurse aide decision-making.
      RESULTS: Findings suggest race among demographic predictors, emotional exhaustion
      among personal characteristics, and supervisor support, and shared governance
      among structural factors, significantly affect nurse aide decision-making.
      CONCLUSION: It is important to explore race as one of the central determinants of
      structural empowerment among nurse aides. In addition, the nature and type of
      emotional exhaustion that propels decision-making needs to be further examined.
      RELEVANCE TO CLINICAL PRACTICE: The study shows the importance of shared
      governance and supervisor support for fostering nurse aide empowerment.

PMID- 23534555
TI  - IL-6 cooperates with peroxisome proliferator-activated receptor-alpha-ligands to
      induce liver fatty acid binding protein (LFABP) up-regulation.
AB  - BACKGROUND: LFABP plays a critical role in the uptake and intracellular transport
      of fatty acids (FA) and other peroxisome proliferator-activated receptor alpha
      (PPARalpha) ligands. PPARalpha activation by PPARalpha ligands bound to LFABP
      results in gene expression of FA oxidation enzymes and de novo LFABP. The
      cytokine IL-6 is involved in regulating liver lipid oxidation. AIMS: To study the
      ability of IL-6 to modulate the expression of the LFABP in hepatocytes. METHODS:
      HepG2 and mouse primary hepatocytes were used to test LFABP mRNA and protein
      expression after IL-6 and PPARalpha-ligand treatments. Mice lacking IL-6 and wild
      type C57Bl/6 were subjected to a fasting/re-feeding cycle to monitor hepatic
      LFABP mRNA kinetics after food intake. RESULTS: In hepatocyte cultures, IL-6
      treatment stimulated a LFABP mRNA sustained expression. Combined treatment of IL
      6 plus PPARalpha ligands further enhanced LFABP gene and protein expression. In
      contrast, pretreatment with the PPARalpha-antagonist GW-6471 prevented the up
      regulation of LFABP mRNA induced by IL-6 in the late phase of LFABP kinetics.
      Furthermore, the up-regulation of LFABP mRNA observed in the liver of wild-type
      mice 8 h after re-feeding was absent in mice lacking IL-6. CONCLUSIONS: IL-6
      induces LFABP kinetics in hepatocytes and is partially dependent on PPARalpha.
      The maximum increase in LFABP expression occurs when the stimulation with IL-6
      and PPARalpha-ligands takes place simultaneously. The in vivo results indicate a
      postprandial regulation of LFABP that correlates with the presence of IL-6. These
      effects may have important implications in the postprandial increase in FA uptake
      and intracellular trafficking in the liver.

PMID- 23534556
TI  - Electrophilic aromatic substitutions of aryltrifluoroborates with retention of
      the BF3- group: quantification of the activating and directing effects of the
      trifluoroborate group.
AB  - Kinetics and mechanisms of transition-metal free reactions of furyl, thienyl and
      indolyl trifluoroborates with benzhydrylium (Ar2CH(+)) and iminium (Me2N(+)?CHR)
      ions have been investigated. In contrast to common belief, substitutions at CH
      positions are often faster than ipso-substitutions of the BF3K group, because
      BF3K activates the position attached to boron by a factor of 10(3)-10(4) while
      adjacent CH positions are activated by factors of 10(5)-10(6). Several reactions
      that have previously been interpreted as ipso-substitutions actually proceed via
      initial substitution at a vicinal or remote CH position, followed by
      protodeborylation. If the proton released during electrophilic substitution at a
      CH position is trapped by a base, the BF3(-) group can be preserved. Remote
      reactions of heteroaryl trifluoroborates with iminium ions provide
      straightforward access to novel zwitterionic ammonium or iminium
      trifluoroborates, which have been characterized by single-crystal X-ray analyses.

PMID- 23534557
TI  - Coassembly in binary mixtures of peptide amphiphiles containing oppositely
      charged residues.
AB  - The self-assembly in water of designed peptide amphiphile (PA) C16-ETTES
      containing two anionic residues and its mixtures with C16-KTTKS containing two
      cationic residues has been investigated. Multiple spectroscopy, microscopy, and
      scattering techniques are used to examine ordering extending from the beta-sheet
      structures up to the fibrillar aggregate structure. The peptide amphiphiles both
      comprise a hexadecyl alkyl chain and a charged pentapeptide headgroup containing
      two charged residues. For C16-ETTES, the critical aggregation concentration was
      determined by fluorescence experiments. FTIR and CD spectroscopy were used to
      examine beta-sheet formation. TEM revealed highly extended tape nanostructures
      with some striped regions corresponding to bilayer structures viewed edge-on.
      Small-angle X-ray scattering showed a main 5.3 nm bilayer spacing along with a 3
      nm spacing. These spacings are assigned respectively to predominant hydrated
      bilayers and a fraction of dehydrated bilayers. Signs of cooperative self
      assembly are observed in the mixtures, including reduced bundling of peptide
      amphiphile aggregates (extended tape structures) and enhanced beta-sheet
      formation.

PMID- 23534559
TI  - The effects of repetitive haemarthrosis on postural balance in children with
      haemophilia.
AB  - Sensory information from visual, vestibular and proprioceptive systems is
      necessary to control posture and balance. Impairment in proprioception due to
      repetitive joints bleeding may lead to a deficit in postural balance which, in
      turn, leads to high joint stress and risk of bleeding recurrence. Despite the
      increase in attention in this field during the past few years, the data
      concerning to how bleeds can affect postural control in children with haemophilia
      (CWH) remain scarce. This study aimed to evaluate the postural balance in CWH.
      Twenty CWH Haemophilia Group (HG) and 20 age-matched children Control Group (CG)
      were recruited to this study. A force plate was used to record centre of pressure
      (COP) displacement under four different postural conditions during quiet
      standing: eyes open on firm surface, eyes open on foam surface, eyes closed on
      firm surface and eyes closed on a foam surface. Variables of COP as sway area and
      mean velocity and in anterior-posterior (y) medio-lateral (x) direction were
      processed and for each variable sensory, quotients were calculated and compared
      between groups. No differences were found in visual and vestibular quotients
      variables between groups. A higher value was found in sway area variable on
      proprioception quotient in the HG when compared with CG (P = 0.042). CWH with
      repetitive joint bleed on lower limbs showed differences in postural balance when
      compared with non-haemophiliac children. The identification of early balance
      impairments in CWH can help us understand better the effects of bleeds inside
      joints on postural control and plan a more effective preventive and
      rehabilitative treatment.

PMID- 23534560
TI  - Multiresidue pesticide analysis of botanical dietary supplements using salt-out
      acetonitrile extraction, solid-phase extraction cleanup column, and gas
      chromatography-triple quadrupole mass spectrometry.
AB  - Dietary supplements form an increasing part of the American diet, yet broadly
      applicable multiresidue pesticide methods have not been evaluated for many of
      these supplements. A method for the analysis of 310 pesticides, isomers, and
      pesticide metabolites in dried botanical dietary supplements has been developed
      and validated. Sample preparation involved acetonitrile:water added to the
      botanical along with anhydrous magnesium sulfate and sodium chloride for
      extraction, followed by cleanup with solid-phase extraction using a tandem
      cartridge consisting of graphitized carbon black (GCB) and primary-secondary
      amine sorbent (PSA). Pesticides were measured by gas chromatography-tandem mass
      spectrometry. Accuracy and precision were evaluated through fortifications of 24
      botanicals at 10, 25, 100, and 500 MUg/kg. Mean pesticide recoveries and relative
      standard deviations (RSDs) for all botanicals were 97%, 91%, 90%, and 90% and
      15%, 10%, 8%, and 6% at 10, 25, 100, and 500 MUg/kg, respectively. The method was
      applied to 21 incurred botanicals. Quinoxyfen was measured in hops (100-620
      MUg/kg). Tetraconazole (48 MUg/kg), tetramethrin (15 MUg/kg), methamidophos (50
      MUg/kg), and chlorpyrifos (93 MUg/kg) were measured in licorice, mallow, tea, and
      tribulus, respectively. Quintozene, its metabolites and contaminants
      (pentachloroaniline, pentachlorobenzene, pentachloroanisole, and
      pentachlorothioanisole and hexachlorobenzene and tecnazene, respectively), with
      hexachlorocyclohexanes and DDT were identified in ginseng sources along with
      azoxystrobin, diazinon, and dimethomorph between 0.7 and 2800 MUg/kg. Validation
      with these botanicals demonstrated the extent of this method's applicability for
      screening 310 pesticides in a wide array of botanical dietary supplements. 

PMID- 23534562
TI  - Salt in health and disease--a delicate balance.

PMID- 23534561
TI  - Clinical practice. Short stature in childhood--challenges and choices.

PMID- 23534563
TI  - Images in clinical medicine. Bulimia nervosa.

PMID- 23534564
TI  - Clinical-outcome trials in cardiac surgery--have we primed the pump?

PMID- 23534565
TI  - Research as a part of public health emergency response.

PMID- 23534566
TI  - Tocilizumab for systemic juvenile idiopathic arthritis.

PMID- 23534567
TI  - Tocilizumab for systemic juvenile idiopathic arthritis.

PMID- 23534568
TI  - Tolvaptan in autosomal dominant polycystic kidney disease.

PMID- 23534569
TI  - Tolvaptan in autosomal dominant polycystic kidney disease.

PMID- 23534570
TI  - Tolvaptan in autosomal dominant polycystic kidney disease.

PMID- 23534571
TI  - Tolvaptan in autosomal dominant polycystic kidney disease.

PMID- 23534572
TI  - Tolvaptan in autosomal dominant polycystic kidney disease.

PMID- 23534573
TI  - Purinergic signaling during inflammation.

PMID- 23534574
TI  - Purinergic signaling during inflammation.

PMID- 23534575
TI  - Case 40-2012: a woman with cardiorespiratory arrest after a cesarean section.

PMID- 23534576
TI  - Case 40-2012: a woman with cardiorespiratory arrest after a cesarean section.

PMID- 23534577
TI  - Maintenance of certification.

PMID- 23534578
TI  - Maintenance of certification.

PMID- 23534579
TI  - Maintenance of certification.

PMID- 23534580
TI  - Maintenance of certification.

PMID- 23534581
TI  - State Medicaid eligibility and care delayed because of cost.

PMID- 23534582
TI  - Videos in clinical medicine. Reduction of paraphimosis in boys.

PMID- 23534583
TI  - Images in clinical medicine. Epidermolysis bullosa acquisita.

PMID- 23534584
TI  - Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene
      polymorphism and left ventricular hypertrophy.
AB  - BACKGROUND: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T
      gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular
      events is controversial. We investigated the relationship of MTHFR 677C>T
      polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency.
      METHODS: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2
      were assessed in 138 non-diabetic subjects (age, 50.93 +/- 14.85 years; body mass
      index, 27.95 +/- 5.98 kg/m(2)), 38 no-mutation wild MTHFR C677CC, 52 heterozygous
      MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to
      current international healthy dietary guidelines. Serum homocysteine, insulin
      resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and
      renal artery resistive index (RRI) were challenged by odds ratio analysis and
      multiple linear regression models. RESULTS: MTHFR 677C>T polymorphism showed
      higher GFR (73.8 +/- 27.99 vs. 58.64 +/- 29.95; p= 0.001) and lower renal failure
      odds (OR, 0.443; 95% confidence interval, 0.141-1.387) in comparison with wild
      MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented
      independently by the negative effects of LVH, increased intra-renal arterial
      resistance, and hyperparathyroidism; GFR is the significant predictive factor to
      LVH. CONCLUSIONS: Renal insufficiency in non-diabetic subjects is explained by
      interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact
      parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is
      opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal
      insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and
      greater hsCRP, iPTH, RRI, and LVH.

PMID- 23534585
TI  - Originals in translation!

PMID- 23534586
TI  - [Depression and suicidal ideation in elderly institutionalized and non
      institutionalized in Portugal].
AB  - INTRODUCTION/OBJECTIVES: Depression has shown as the more common mental disorder
      in elderly community and suicide is it worst consequence. In the Portuguese
      context suicide rates among the elderly take values higher than in other age
      groups. The present study aimed to compare elderly institutionalized and not
      institutionalized in terms of depression, suicidal ideation, dependency and
      leisure activities. MATERIAL AND METHODS: The sample was collected in Algarve,
      Alentejo and Lisbon, in 155 elderly, 85 institutionalized and 71 not
      institutionalized, with similar proportions between genders. The instruments were
      The Activity and Leisure Index (IAL), the Geriatric Depression Scale (GDS), The
      Barthel Index and the Beck Scale for Suicide Ideation (BSI). RESULTS: The results
      showed that the elderly institutionalized did not presented higher depression,
      loneliness, suicidal thoughts or lowest level of activity and leisure, but were
      less independent. The participants with highest suicidal thoughts had more
      depression. A self-perception of worse health and more loneliness were related
      with more depression. A higher activity and leisure was related with less
      suicidal ideation. CONCLUSIONS: The data seem to show that the
      institutionalization of elderly is not related negatively with depression and
      suicidal ideation.

PMID- 23534587
TI  - MRI of pregnant patients for suspected pulmonary embolism: steady-state free
      precession vs postgadolinium 3D-GRE.
AB  - INTRODUCTION: Pulmonary embolism is a leading cause of maternal mortality in the
      developed world. Ventilation-perfusion scintigraphy and Computer tomography cause
      ionizing radiation exposure. Gadolinium-enhanced magnetic resonance imaging is
      generally not indicated in pregnant patients. MRI using motion resistant
      techniques that do not use intravenous contrast material, such as balanced steady
      state free precession may be a better approach in pregnant patients. PURPOSE: To
      describe the preliminary findings of the use of SSFP for the evaluation of
      pregnant patients with suspected PE, and to compare with a young women population
      evaluated with postgadolinium 3D-gradient echo sequences for the same intention.
      MATERIALS AND METHODS: Radiology database was searched for two groups of subjects
      who underwent chest MRI at 1.5T for suspected PE, between January, 2007 and June,
      2010: pregnant patients with MRI including balanced SSFP (group A) and females
      younger than 45 years old including a T1-weighted postgadolinium 3D-GRE (group B)
      sequence. The final study population consisted of 21 subjects. Blind and
      independent evaluation of MR images was performed for image quality of the
      pulmonary arterial system, PE and other chest findings. Data was subject to
      statistical analysis. RESULTS: Good image quality was observed in all central and
      lobar arteries on both groups and in 90% (group A) and at least 83.3% (group B)
      of the segmental arteries. There was no significant difference between groups A
      and B for image quality of central and lobar pulmonary arteries (p > 0.05).
      CONCLUSION: SSFP can visualize central, lobar and segmental pulmonary arteries
      with sufficient image quality in pregnant patients, comparable to 3D-GRE.

PMID- 23534588
TI  - [Neonatal seizures in a tertiary neonatal intensive care unit].
AB  - INTRODUCTION: Seizures are frequent in the neonatal period. They can be
      idiopathic, be caused by organic brain anomalies or by metabolic disturbances.
      OBJECTIVE: Evaluation of the etiologic diagnosis and clinical evolution of the
      newborns with neonatal seizures admitted at one tertiary neonatal intensive care
      unit. MATERIAL AND METHODS: Retrospective review of the clinical files of the
      newborns with neonatal seizures, during a period of eight years. RESULTS:
      Neonatal seizures occurred in 91 cases. Seventy nine (86.8%) received
      anticonvulsant therapy during clinical seizure. Image and/or electrophysiological
      studies were performed in the majority of newborns (86.8%). Etiology was
      identified in 51.6% of the 91 cases studied, being the more frequent situations:
      central nervous system bleeding (11 cases), hypoxic-ischemic encephalopathy (10
      cases) and electrolytes disturbances (7 cases). Mortality rate was 16.5%. The
      newborns followed in our hospital had good neurodevelopment, in 70.2% of cases
      but in 10.6% was detected important neurodevelopment impairment, including
      cerebral palsy. CONCLUSIONS: Anomalies in the cranial ultrasound and in the
      electroencephalography were correlated with clinical evolution. They still are
      first line exams in the initial approach to this pathology.

PMID- 23534589
TI  - [Health system in the Health Region of Lisbon and Tagus Valley: beyond health
      centers and hospitals].
AB  - INTRODUCTION: This article describes the economic health complex in the Health
      Region of Lisbon and the Tagus River. MATERIAL AND METHODS: Databases for 2007,
      for enterprises, establishments and human resources, were made available by the
      Office of Strategy and Planning of the Ministry of Employment and Social
      Solidarity for the Health Region of Lisbon and the Tagus River. Also for the
      Health Region of Lisbon and the Tagus River, public sector hospital and health
      centre data was made available by the National, Statistics Office. The data were
      analyzed, with georeferentiation when relevant. RESULTS: The results allow a
      first glimpse of the economic health complex of the largest health region of
      Portugal. This economic complex includes 7180 enterprises and 8504 establishments
      with a staff establishment of 127 430. CONCLUSION: There are four large areas of
      health related economic activities: healthcare provision (mostly in the public
      sector), social support, commercialization of medicines and health products and
      other activities. The three last categories are mostly in the private sector.

PMID- 23534590
TI  - [Cerebral creatine deficiency syndromes].
AB  - INTRODUCTION: Creatine deficiency syndromes are a recently described group of
      diseases characterized by inborn errors of creatine metabolism. Clinical features
      include a spectrum of neurodevelopment disorders of diverse severity. They are
      characterized by low levels of cerebral creatine caused by different pathogenic
      mutations concerning the genes coding for creatine synthesis enzymes [arginine:
      glicyne amidinotransferase (AGAT, EC 2.1.4.1) and guanidinoacetate
      methyltansferase (GAMT, EC 2.1.1.2)], AGAT and GAMT, respectively, or its
      transporter (CT1 deficiency), SLC6A8. Enzymatic deficiencies are transmitted as
      autosomal recessive traits, whereas the transporter deficit is X-linked.
      OBJECTIVES: To characterize the clinical and laboratorial presentation, diagnosis
      and treatment of cerebral creatine deficiency patients, followed in Hospital
      Pediatrico Carmona da Mota. The awareness of these inborn errors of metabolism as
      neurological disorders, namely of neurodevelopment, among the medical community
      is a secondary aim of the present work. METHODS AND MATERIAL: Retrospective
      analysis of the clinical files of patients followed in our Hospital and diagnosed
      with cerebral creatine deficiency syndrome. RESULTS: Twelve patients belonging to
      seven different families were diagnosed with creatine deficiency syndromes. Five
      presented GAMT deficiency and seven CT1 deficiency. Present ages are 2 to 38
      years old. The most common clinical presentations were: global development delay
      in seven patients (two with epilepsy), and speech delay in two patients. Only one
      patient had communication and social interaction dysfunction. In all, global
      development delay in the range of intellectual delay was identified. The
      pathognomonic pattern of cerebral creatine deficiency in the brain image was
      demonstrated in eight patients. Pathogenic mutations in GAMT or SLC6A8 genes were
      identified in all cases. CONCLUSIONS: The suspicion of cerebral creatine
      depletion must be considered in all children presenting unexplained global
      psychomotor development delay. Pre-symptomatic therapy has shown promising
      results, especially in GAMT deficiency patients. The high rate of asymptomatic
      carriers of GAMT mutations in our population makes this disorder eligible to
      neonatal screening in Portugal.

PMID- 23534591
TI  - [DNA ploidy is an independent prognostic biomarker in breast invasive ductal
      carcinoma].
AB  - OBJECTIVE: To evaluate 'classic' prognostic parameters, as well as DNA ploidy and
      S-phase fraction, in relation to disease-free and overall survival in breast
      invasive ductal carcinoma with long-term follow-up. MATERIAL AND METHODS: The
      study involved 400 patients with breast invasive ductal carcinoma and median
      follow-up of 134 months (50-240). Histological grading, tumour size, axillary
      nodal involvement, pathological staging and hormone-receptor status were assessed
      as established prognostic markers. Ploidy and S-phase fraction were determined
      prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression
      model was used for statistical analysis of the prognostic variables. RESULTS:
      There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow
      up. Two hundred thirty-five (58.7%) tumours were aneuploid. High S-phase fraction
      and aneuploidy were associated with tumours with higher grade of differentiation,
      greater size and negative hormonal receptors. In univariate analysis, all the
      clinicopathological and cytometric features (including patients < 40 years and a
      subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and
      estrogen receptors for disease free survival, significantly correlated with
      clinical outcome. In multivariate analysis, advanced disease stage, DNA
      aneuploidy and lack of progesterone receptors retained statistically significant
      association with shorter survival. In the subgroup of patients with intermediate
      differentiation tumours (G2), aneuploidy associated with worse prognosis. In the
      subset of node-negative patients, only estrogen receptors showed significant
      correlation with disease evolution. In node-positive patients, greater size
      tumours and aneuploidy (in relation to overall survival) were indicators of worse
      prognosis. CONCLUSION: Along with disease staging and hormone-receptor
      expression, DNA ploidy is an independent prognostic biomarker of long-term
      survival in breast invasive ductal carcinoma.

PMID- 23534592
TI  - [Evaluation of the reasons underlying drop-out and identification of predictive
      factors in psychiatric patients].
AB  - INTRODUCTION/OBJECTIVES: The evaluation of psychiatric interventions results
      should be multidimensional, including clinical and social variables, such as
      individual experience of the mentally ill. The patient satisfaction with care has
      been recognized as an important variable, despite not being the main objective of
      the service or of the psychiatrist. However, if the user's perspective is not
      included, there's a risk of bias by the perception of the heath care providers.
      In this study, our aim was to understand if the abandonment of treatment (drop
      out) represents an improvement or worsening of subjective well-being of patients
      and / or dissatisfaction with the services received, as well as to find
      predictors of drop-out. MATERIAL AND METHODS: Identification of drop-outs in a 2
      year cohort of patients who had initial psychiatric consultations in the
      Psychiatric Unit at Centro Hospitalar do Medio Ave - Unidade de Famalicao (Local
      Mental Health Service). RESULTS: We identified 512 patients who had a first
      psychiatric consultation, 57 of which unilaterally abandoned the treatment for at
      least six months, without making any contacts in order to reschedule the
      appointment during this period. Of these only 38 completed the assessment
      (telephone response to a semi-structured questionnaire). Three predictive factors
      for the drop-out were found: age, education and diagnosis. CONCLUSIONS: The
      reasons for treatment abandonment focused mainly in forgetfulness and
      dissatisfaction, the last one involving doctor-patient relationship issues. These
      results should be a starting point for assessing and improving care.

PMID- 23534593
TI  - [Virtual reality and rehabilitation: why or why not? A systematic literature
      review].
AB  - Regardless of the health domain involved, the process of rehabilitation remains a
      challenge for professionals, patients and their families. In an attempt to
      overcome the limitations of traditional interventions, the technology of Virtual
      Reality (VR) has been increasingly applied to rehabilitation and begins to
      provide important tools which, however, generate debate and divergent positions.
      In order to examine VR's contributions to the field of rehabilitation in terms of
      its advantages and limitations, this study presents a systematic review of
      scientific literature in this area and provides a hierarchical model describing
      and systematizing the nature of the studies reviewed and their main subjects. The
      literature review focused on scientific papers indexed, until November 2010, in
      the ISI Web of Knowledge databases. Two independent researchers analyzed the
      included papers in NVivo 9 and the developed model was applied to the recoding of
      the material. A total of 963 articles were identified, of which 288 titles and
      abstracts were reviewed, after application of the exclusion criteria. The model
      indicates, as central categories in the literature: Type of Article (Empirical,
      Theoretical); Project Background; Type of Approach (Assistive Technology;
      Augmented Reality; Traditional Approaches; Virtual Reality). This last category
      (VR) was exhaustively decomposed so that its applicability, effects and future
      trends could be documented. Results suggest that VR's advantages include: its
      possible application to a variety of fields, cognitive functions, behaviors,
      neurological disorders and physical disabilities; its characteristics and
      respective consequences; and its potential to overcome limitations of traditional
      interventions. On the side of the limitations, papers address: VR's side effects,
      causes for the limitations, and suggested precautions. The results show promising
      trends in the use of VR technology in the field of rehabilitation, with
      implications for its future implementation. Results further indicate the need for
      continuing research that evaluates VR's applicability to rehabilitation in
      general and (neuro)cognitive rehabilitation in particular.

PMID- 23534594
TI  - [Neoadjuvant radiotherapy and hormonotherapy in locally advanced breast cancer:
      state of the art].
AB  - INTRODUCTION: Breast cancer is a health problem of great magnitude. In recent
      years we have seen an increasing incidence and decreasing mortality from this
      disease due to implementation of campaigns for early diagnosis and the
      effectiveness of existing treatments. For more than a century that we know the
      evidence that growth and development of some tumours depends in part on hormonal
      stimuli, and the purpose of hormone therapy to prevent the hormonal stimulation
      of cell proliferation, decreasing the plasma levels of different hormones.
      Radiotherapy which uses a controlled ionizing radiation for therapeutic purposes,
      it is one of the fundamental modalities in the treatment of cancer. According to
      the international guidelines these modalities of treatment, radiotherapy and
      hormone therapy, can be used in the treatment of breast cancer both within the
      neoadjuvant, adjuvant or palliative treatment. OBJECTIVES: Obtain data to support
      or not the use of concomitant radiotherapy and neoadjuvant hormone therapy
      instead to neoadjuvante chemotherapy in post menopausal patients diagnosed with
      locally advanced breast cancer and positive hormone receptors. METHODS:
      Bibliographic search in MEDLINE databases, and evidence based review databases,
      using the MeSH terms: Radiotherapy, Hormonotherapy, Tamoxifen, Neoadjuvant,
      Endocrine Therapy, Breast of articles published at any time and in English,
      Portuguese, French and Spanish. It was also researched the Index of Portuguese
      Medical Journal and scientific societies dedicated to Oncology. RESULTS: We
      analyzed 32 studies (in vitro experiments, animal studies and clinical studies).
      There was the existence of antagonistic interaction between Radiotherapy and
      Tamoxifen in the in vitro studies, which has not been confirmed in the animal
      studies and clinical trial. Clinical studies suggest that a combination of
      radiotherapy and Tamoxifen increases the local control in the in situ carcinoma
      like in the invasive breast cancer. The available clinical studies do not
      demonstrate that the simultaneous application of Radiotherapy and tamoxifen is
      disadvantageous, as suggested in the in vitro studies. However, the tolerance of
      lung tissue to radiation may be slightly reduced if tamoxifen is given
      concurrently with radiotherapy, such as swelling of the breast and its duration
      can be increased. The cosmetic results were not harmed in the combined treatment,
      except for one study where there was an increased of hyperpigmentation. Finally,
      the combined treatment was an increase in cardiovascular events. CONCLUSIONS: In
      the literature there are few studies on these issues, most of which are adjuvant
      intention in women with breast cancer at an early stage, and the results are
      inconclusive. There is great uncertainty in the combination of the two
      modalities. There isn't a randomized study where differences in local control
      when hormonotherapy is initiated before, during or after radiation therapy were
      investigated.

PMID- 23534595
TI  - [Identification of therapeutic and diagnostic targets through yeast two hybrid
      system: molecular biology in medicine].
AB  - In the last decades, molecular biology development was driven medicine, mainly in
      identification of novel therapeutic and diagnostics targets. In cells, proteins
      are the main responsible for the functioning of all cellular processes, from DNA
      synthesis to RNA and protein production, transport of cellular components and
      structural composition of the cell. Proteins are also an important component of
      signaling pathways between cells. Studies show that proteins normally do not
      function as singular units but as protein complexes. Understand protein
      interactions and discover compounds that interfere with such protein complexes
      are important to develop new pharmacologic treatments. There are already some
      drugs with such characteristics. Trichostatin A, a histone diacetilase, acts in
      Phosphatase protein 1 - Histone diacetilase complex, being a good target for anti
      cancer therapy. In 1989, in a revolutionary way, Fields and Songs developed the
      Yeast Two Hybrid system (YTH). This method is based in the genetic properties of
      Saccharomyces cerevisiae and allows the detection of protein interactions in
      vivo. Since its development it suffered a few modifications that allowed its
      application in translational medicine. For example, this technique allows a high
      throughput screening to assess if a drug can interfere with a protein
      interaction. In the other hand, YTH can be used to ascertain which proteins
      interact with a protein of interest in a specific tissue (for example, brain or
      testis). Thus it is possible to unveil protein functions, signaling pathways and
      tissue functions. The great amount of data produced with YTH allows the
      identification and validation of diagnostic and therapeutic targets and also the
      development of new drugs. This review has the purpose to clarify the YTH system
      function and its contribution in identification of new pharmacologic treatments.

PMID- 23534596
TI  - [Hereditary thrombophilia and pregnancy: thrombotic risk and pregnancy outcome].
AB  - Thromboembolic disease and obstetric complications related to ischemia of the
      placenta are currently the major causes of maternal mortality and morbidity.
      Thrombophilia been implicated in their aetiology and the magnitude of the risk
      depends on the type of thrombophilia. As the evidence is still unclear and
      controversial, questions about the clinical management of pregnant women with
      thrombophilia are a daily issue. We aim to review, bearing in mind the consensus
      and controversies, the impact of inherited thrombophilia in the risk of
      thrombosis related to pregnancy and of obstetric complications. Moreover, the
      diagnostic, preventive and therapeutic approach during pregnancy and puerperium,
      including the role of antithrombotic pharmacopoeia available, will be discussed.

PMID- 23534597
TI  - [Chocolate craving].
AB  - Chocolate craving can be defined as an intense, intrusive and irrepressible
      desire for the consumption of chocolate. It is a fairly unknown clinical reality,
      for which it is important to raise awareness among health care professionals and
      other interested people. This paper reviews the pathophysiology, epidemiology,
      diagnosis, complications, treatment and prevention of chocolate craving, based on
      a systematic review and reading of 57 articles published in the last decades
      about the subject. This review shows that chocolate craving is associated with
      many health problems, such as obesity, depression, anxiety and substance misuse.
      Since there is no specific treatment for chocolate craving, its therapeutic
      approach is based on psychological strategies and on the therapeutic strategies
      for addition, obesity and other conditions related to chocolate craving.

PMID- 23534598
TI  - [Systemic lupus erythematosus and pregnancy].
AB  - Systemic lupus erythematosus is a chronic inflammatory disease, resulting from an
      auto-immune dysfunction. The etiology of this disease is unknown. It frequently
      occurs in women of childbearing age. Pregnancy in patients with systemic lupus
      erythematosus may be associated with several complications (maternal, obstetrical
      and fetal). The prognosis for both mother and child is better when systemic lupus
      erythematosus has been quiescent for at least six months before pregnancy. Thus,
      preconceptional assessment and management is crucial for helping women to achieve
      a period of disease remission before pregnancy as well as for allowing an
      adjustment of therapy. Maternal health and fetal development should be closely
      monitored during pregnancy. These patients should be surveilled by a
      multidisciplinary team (obstetrician, rheumatologist or internist, nephrologist
      if necessary and a pediatrician), in a tertiary care hospital. Antiphospholipid
      syndrome, positivity for anti-SSA/Ro or anti-SSB/LA antibodies, hypertension or
      renal involvement are associated with an increase of adverse pregnancy outcomes.
      In this article the authors review the main aspects of Systemic lupus
      erythematosus (SLE) and pregnancy.

PMID- 23534599
TI  - [Hypoglycemia in the diabetic patient: the controversy in its study, in search of
      its implications].
AB  - Hypoglycemia is one of the greatest limitations regarding the treatment of
      diabetes, as well as one of the most expensive. Its relevance goes beyond the
      episode itself or the rare sequel. The occurrence of hypoglycemia is frequently
      followed by treatment adjustments involving the glycemic target, which can result
      in long term diabetes complications. Its medium and long term consequences are
      not yet understood in light of recent studies, which have renewed fears regarding
      an increased cardiovascular risk with its occurrence. Controversy around its
      definition, as well as serious methodological limitations, led to disparities
      between the results of the multiple studies of incidence and costs. The low
      adhesion of a significant number of diabetic patients to glycemic self-monitoring
      during symptomatic episodes leads to diagnostic uncertainty and, occasionally, to
      a worsening of the glycemic control. The health-care based studies result in
      great underestimation of its incidence given the fact that many episodes are mild
      in nature, and some severe hypoglycemic episodes are treated by the patient's
      family or friends. Recent studies revealed that a significant number of severe
      hypoglycemic episodes treated by health-care professionals doesn't involve
      transportation to an Emergency Department. The same data suggest that the largest
      portion of the direct and indirect costs of diabetic hypoglycemia is related to
      the episodes that are treated at the Hospital, particularly if the patient is
      admitted in the ward. In the past decades a great investment has been made in the
      development of multiple strategies for the avoidance of hypoglycemia, namely the
      continuous blood glucose monitoring devices, as well as new drugs. In spite of
      the efforts, hypoglycemia remains as one of the most important problems in the
      treatment of diabetes.

PMID- 23534600
TI  - [Spinal cord compression by testicular germ cell tumor: case report].
AB  - Malignant spinal cord compression occurs in 2.5% - 5% cancer patients. Early
      diagnosis and therapeutic intervention are critical for pain control and
      improvement of any neurological deficit. Treatment should be directed to the
      underlying disease together with appropriate symptom management. The case of a
      man with tetraparesis of 24 hours duration is presented. He had surgery five days
      earlier because of a testicular tumor and spinal magnetic resonance imaging (MRI)
      showed spinal cord compression by a soft tissue mass between C7 and D2. After
      confirming the diagnosis of mixed germ cell tumor, stage IIIC, the patient began
      chemotherapy with progressive neurological improvement. Two years after diagnosis
      the patient presents a slight reduction of strength in the right hand and remains
      without any evidence of disease. This case illustrates the importance of early
      diagnosis of spinal cord compression and one of the main indications for the use
      of chemotherapy as the treatment for an oncologic emergency.

PMID- 23534601
TI  - [A case of successful treatment of concomitant ruptured intracranial aneurysm and
      visceral aneurysm].
AB  - The association between intracranial and visceral aneurysms is very rare, with a
      bad prognosis. The rupture usually appears in the Emergency Room, and it implies
      an immediate treatment. We describe the case of a woman with rupture of an
      anterior communicant artery aneurysm and rupture of a pancreatic duodenal artery
      aneurysm. The actuation of all specialties allowed the direct surgical treatment
      of the visceral aneurysm, without the aggravation of the cerebral hemorrhage that
      the eventual Aorta Artery clamping could provoke. The maintenance of the
      hemodynamic stability was essential for the posterior treatment of the
      intracranial aneurysm.

PMID- 23534602
TI  - [Esophageal perforation with acute mediastinitis].

PMID- 23534603
TI  - [Renal osteodystrophy].

PMID- 23534604
TI  - Self-construction of magnetic hollow La0.7Sr0.3MnO3 microspheres with complex
      units.
AB  - Perovskite structure La0.7Sr0.3MnO3 magnetic hollow microspheres with complex
      units were prepared via the hydrothermal route without hard and soft templates.
      The formation of hollow microspheres follows the self-construction mechanism
      involving oriented attachment, dissolution, and recrystallization processes. It
      exhibits a ferromagnetic behavior at room temperature.

PMID- 23534605
TI  - Geranylgeranyltransferase I mediates BDNF-induced synaptogenesis.
AB  - Geranylgeranyltransferase I (GGT) is a prenyltransferase that mediates lipid
      modification of Rho small GTPases, such as Rho, Rac, and Cdc42, which are
      important for neuronal synaptogenesis. Although GGT is expressed in brain
      extensively, the function of GGT in central nerves system is largely unknown so
      far. We have previously demonstrated that GGT promotes the basal and neuronal
      activity and brain-derived neurotrophic factor (BDNF)-induced dendritic
      morphogenesis of cultured hippocampal neurons and cerebellar slices. This study
      is to explore the function and mechanism of GGT in neuronal synaptogenesis. We
      found that the protein level and activity of GGT gradually increased in rat
      hippocampus from P7 to P28 and subcellular located at synapse of neurons. The
      linear density of Synapsin 1 and post-synaptic density protein 95 increased by
      over-expression of GGT beta, while reduced by inhibition or down-regulation of
      GGT. In addition, GGT and its known substrate Rac was activated by BDNF, which
      promotes synaptogenesis in cultured hippocampal neurons. Furthermore, BDNF
      induced synaptogenesis was eliminated by GGT inhibition or down-regulation, as
      well as by non-prenylated Rac1 over-expression. Together, our data suggested that
      GGT mediates BDNF-induced neuronal synaptogenesis through Rac1 activation.

PMID- 23534606
TI  - Predictions of phase separation in three-component lipid membranes by the MARTINI
      force field.
AB  - The phase behavior of the coarse-grained MARTINI model for three-component lipid
      bilayers composed of dipalmytoyl-phosphatidylcholine (DPPC), cholesterol (Chol),
      and an unsaturated phosphatidylcholine (PC) was systematically investigated by
      molecular dynamics simulations. The aim of this study is to understand which
      types of unsaturated PC induce the formation of thermodynamically stable
      coexisting phases when added to mixtures of DPPC and Chol and to unravel the
      mechanisms that drive phase separation in such three-component mixtures. Our
      simulations indicate that the currently used MARTINI force field does not induce
      such phase separation in mixtures of DPPC, Chol, and unsaturated PCs with a low
      unsaturation level, such as palmitoyl-oleoyl-phosphatidylcholine (POPC) or
      dioleoyl-phosphatidylcholine (DOPC). Also, we found that phase separation does
      occur in mixtures of DPPC, Chol, and polyunsaturated PCs, such as dilinoleyl
      phosphatidylcholine (DUPC) and diarachidonoyl-phosphatidylcholine (DAPC). Through
      systematic tweaking of the interactions between the hydrophobic groups of the PC
      molecules, we show that the appearance of phase separation in three-component
      lipid bilayers, as modeled through the MARTINI force field, is primarily due to
      the interactions between the coarse-grained molecules, i.e., the beads, rather
      than due to the differences between the conformations of saturated and
      unsaturated lipid acyl chains, namely entropy driven.

PMID- 23534607
TI  - Early childhood housing instability and school readiness.
AB  - This study assesses the consequences of housing instability during the first 5
      years of a child's life for a host of school readiness outcomes. Using data from
      the Fragile Families and Child Wellbeing Study (n = 2,810), this study examines
      the relation between multiple moves and children's language and literacy and
      behavior problems at age 5. The moderating role of poverty is further tested in
      this relation. The findings show that moving three or more times in a child's
      first 5 years is significantly associated with increases in attention problems,
      and internalizing and externalizing behavior, but only among poor children. 

PMID- 23534608
TI  - RNAseq-based transcriptome analysis of Lactuca sativa infected by the fungal
      necrotroph Botrytis cinerea.
AB  - The fungal pathogen Botrytis cinerea establishes a necrotrophic interaction with
      its host plants, including lettuce (Lactuca sativa), causing it to wilt, collapse
      and eventually dry up and die, which results in serious economic losses. Global
      expression profiling using RNAseq and the newly sequenced lettuce genome
      identified a complex network of genes involved in the lettuce-B. cinerea
      interaction. The observed high number of differentially expressed genes allowed
      us to classify them according to the biological pathways in which they are
      implicated, generating a holistic picture. Most pronounced were the induction of
      the phenylpropanoid pathway and terpenoid biosynthesis, whereas photosynthesis
      was globally down-regulated at 48 h post-inoculation. Large-scale comparison with
      data available on the interaction of B. cinerea with the model plant Arabidopsis
      thaliana revealed both general and species-specific responses to infection with
      this pathogen. Surprisingly, expression analysis of selected genes could not
      detect significant systemic transcriptional alterations in lettuce leaves distant
      from the inoculation site. Additionally, we assessed the response of these
      lettuce genes to a biotrophic pathogen, Bremia lactucae, revealing that similar
      pathways are induced during compatible interactions of lettuce with necrotrophic
      and biotrophic pathogens. 

PMID- 23534609
TI  - Mesenchymal stem cells protect against neonatal rat hyperoxic lung injury.
AB  - OBJECTIVES: Bronchopulmonary dysplasia (BPD) is a significant global health
      problem and currently lacks effective therapy. We established a neonatal rat
      model of BPD to investigate therapeutic potential of bone marrow-derived
      mesenchymal stem cells (BMSCs) in neonatal hyperoxic lung injury. METHODS: BMSCs
      were isolated, identified, and transfected by lentiviral vector carrying green
      fluorescent protein gene in vitro. Neonatal Sprague-Dawley rats were injected
      intravenously with either BMSCs or phosphate-buffered saline following 95% oxygen
      exposure, and assessed for the survival rate and alveolar injury during recovery.
      RESULTS: Treatment with BMSCs after oxygen exposure for 7 days improved survival
      of neonatal rat during recovery. BMSCs protected against neonatal rat hyperoxic
      lung injury during recovery as demonstrated by enhanced expression of AQP5 and SP
      C, likely due to the suppression of alveolar cell apoptosis and lung inflammation
      responses to oxygen with up-regulation of the expression of BCL-2 gene and down
      regulation of the expression of BAX gene and stimulation of vascular endothelial
      growth factor and so on. CONCLUSIONS: BMSCs protect against O2-mediated injury
      partially through stimulation of potent mediators that participate in tissue
      repair.

PMID- 23534610
TI  - Bismuth iodoform paraffin paste: a review.

PMID- 23534611
TI  - Resection of an intrapericardial lipoma with nonsustained ventricular
      tachycardia.
AB  - A 35-year-old female presented with nonsustained ventricular tachycardia (NSVT)
      and a large intrapericardial mass. The mass was attached to the left ventricular
      wall with a broad stalk. On histopathology, the tumor was diagnosed as a lipoma.
      Postoperatively, the NSVT disappeared.

PMID- 23534612
TI  - Drugs, non-drugs, and disease category specificity: organ effects by ligand
      pharmacology.
AB  - Important understanding can be gained from using molecular biology-based and
      chemistry-based techniques together. Bayesian classifiers have thus been
      developed in the present work using several statistically significant molecular
      properties of compiled datasets of drugs and non-drugs, including their disease
      category or organ. The results show they provide a useful classification and
      simplicity of several different ligand efficiencies and molecular properties.
      Early recall of drugs among non-drugs using the classifiers as a ranking tool is
      also provided. As the chemical space of compounds is addressed together with
      their anatomical characterization, chemical libraries can be improved to select
      for specific organ or disease. Eventually, by including even finer detail, the
      method may help in designing libraries with specific pharmacological or
      toxicological target chemical space. Alternatively, a lack of statistically
      significant differences in property density distributions may help in further
      describing compounds with possibility of activity on several organs or disease
      groups, and given their very similar or considerably overlapping chemical space,
      therefore wanted or unwanted side-effects. The overlaps between densities for
      several properties of organs or disease categories were calculated by integrating
      the area under the curves where they intersect. The naive Bayesian classifiers
      are readily built, fast to score, and easily interpretable.

PMID- 23534613
TI  - Ion transport through lipid bilayers by synthetic ionophores: modulation of
      activity and selectivity.
AB  - The ion-coupled processes that occur in the plasma membrane regulate the cell
      machineries in all the living organisms. The details of the chemical events that
      allow ion transport in biological systems remain elusive. However, investigations
      of the structure and function of natural and artificial transporters has led to
      increasing insights about the conductance mechanisms. Since the publication of
      the first successful artificial system by Tabushi and co-workers in 1982,
      synthetic chemists have designed and constructed a variety of chemically diverse
      and effective low molecular weight ionophores. Despite their relative structural
      simplicity, ionophores must satisfy several requirements. They must partition in
      the membrane, interact specifically with ions, shield them from the hydrocarbon
      core of the phospholipid bilayer, and transport ions from one side of the
      membrane to the other. All these attributes require amphipathic molecules in
      which the polar donor set used for ion recognition (usually oxygens for cations
      and hydrogen bond donors for anions) is arranged on a lipophilic organic
      scaffold. Playing with these two structural motifs, donor atoms and scaffolds,
      researchers have constructed a variety of different ionophores, and we describe a
      subset of interesting examples in this Account. Despite the ample structural
      diversity, structure/activity relationships studies reveal common features. Even
      when they include different hydrophilic moieties (oxyethylene chains, free
      hydroxyl, etc.) and scaffolds (steroid derivatives, neutral or polar macrocycles,
      etc.), amphipathic molecules, that cannot span the entire phospholipid bilayer,
      generate defects in the contact zone between the ionophore and the lipids and
      increase the permeability in the bulk membrane. Therefore, topologically complex
      structures that span the entire membrane are needed to elicit channel-like and
      ion selective behaviors. In particular the alternate-calix[4]arene macrocycle
      proved to be a versatile platform to obtain 3D-structures that can form
      unimolecular channels in membranes. In these systems, the selection of proper
      donor groups allows us to control the ion selectivity of the process. We can
      switch from cation to anion transport by substituting protonated amines for the
      oxygen donors. Large and stable tubular structures with nanometric sized
      transmembrane nanopores that provide ample internal space represent a different
      approach for the preparation of synthetic ion channels. We used the metal
      mediated self-assembly of porphyrin ligands with Re(I) corners as a new method
      for producing to robust channel-like structures. Such structures can survive in
      the complex membrane environment and show interesting ionophoric behavior. In
      addition to the development of new design principles, the selective modification
      of the biological membrane permeability could lead to important developments in
      medicine and technology. 

PMID- 23534614
TI  - Life activities improve heart rate variability in patients with mild hypertension
      and/or the initial stage of heart failure.
AB  - AIMS AND OBJECTIVES: To determine the effects on heart rate variability of home
      based daily activity in patients with mild hypertension and/or stable angina
      pectoris and to clarify the relationship between daily activity and sympathovagal
      balance. BACKGROUND: Several prior studies have assessed the ability of exercise
      training to improve functional capacity and produce beneficial effects on
      mortality and physical capacity in patients with cardiovascular disease. DESIGN:
      A non-randomised six-month prospective longitudinal study. METHODS: This study
      consisted of 41 patients (59-83 years old) with mild hypertension and/or stable
      angina pectoris. The home-based daily activity and heart rate variability were
      measured at the start of the study (BASE) and six months after the start of the
      study (6MoA). At 6MoA, the active mass increased in 23 patients (the IC group),
      while it decreased in the remaining 18 patients (the DC group). RESULTS: There
      were significant increases in the high-frequency component in the IC group
      between the data at BASE and 6MoA. There were significant decreases in the low
      frequency to high-frequency ratio (low frequency/high-frequency) during sleep in
      the IC group between the data at BASE and 6MoA. The active mass was classified
      into life activities and walk activities in terms of intensity of activity. In a
      multivariate model, increased life activitiesrevealed a trend towards an
      association with increased high-frequency. CONCLUSIONS: In patients with mild
      hypertension and/or stable angina pectoris, an increase in active mass improved
      heart rate variability outcomes with increased high-frequency and decreased low
      frequency/high-frequency during sleep. To increase life activitiesmight improve
      heart rate variability and prognosis in patients. RELEVANCE TO CLINICAL PRACTICE:
      This study demonstrated that the potential importance of low-intensity daily
      activities in patients with mild hypertension and/or stable angina pectoris.

PMID- 23534615
TI  - Directing chondrogenesis of stem cells with specific blends of cellulose and
      silk.
AB  - Biomaterials that can stimulate stem cell differentiation without growth factor
      supplementation provide potent and cost-effective scaffolds for regenerative
      medicine. We hypothesize that a scaffold prepared from cellulose and silk blends
      can direct stem cell chondrogenic fate. We systematically prepared cellulose
      blends with silk at different compositions using an environmentally benign
      processing method based on ionic liquids as a common solvent. We tested the
      effect of blend compositions on the physical properties of the materials as well
      as on their ability to support mesenchymal stem cell (MSC) growth and
      chondrogenic differentiation. The stiffness and tensile strength of cellulose was
      significantly reduced by blending with silk. The characterized materials were
      tested using MSCs derived from four different patients. Growing MSCs on a
      specific blend combination of cellulose and silk in a 75:25 ratio significantly
      upregulated the chondrogenic marker genes SOX9, aggrecan, and type II collagen in
      the absence of specific growth factors. This chondrogenic effect was neither
      found with neat cellulose nor the cellulose/silk 50:50 blend composition. No
      adipogenic or osteogenic differentiation was detected on the blends, suggesting
      that the cellulose/silk 75:25 blend induced specific stem cell differentiation
      into the chondrogenic lineage without addition of the soluble growth factor TGF
      beta. The cellulose/silk blend we identified can be used both for in vitro tissue
      engineering and as an implantable device for stimulating endogenous stem cells to
      initiate cartilage repair.

PMID- 23534617
TI  - Amyotrophic lateral sclerosis: targeting the body's energy engine.

PMID- 23534618
TI  - Effect of surface charge density on the affinity of oxide nanoparticles for the
      vapor-water interface.
AB  - Using in-situ X-ray photoelectron spectroscopy at the vapor-water interface, the
      affinity of nanometer-sized silica colloids to adsorb at the interface is shown
      to depend on colloid surface charge density. In aqueous suspensions at pH 10
      corrected Debye-Huckel theory for surface complexation calculations predict that
      smaller silica colloids have increased negative surface charge density that
      originates from enhanced screening of deprotonated silanol groups (=Si-O(-)) by
      counterions in the condensed ion layer. The increased negative surface charge
      density results in an electrostatic repulsion from the vapor-water interface that
      is seen to a lesser extent for larger particles that have a reduced charge
      density in the XPS measurements. We compare the results and interpretation of the
      in-situ XPS and corrected Debye-Huckel theory for surface complexation
      calculations with traditional surface tension measurements. Our results show that
      controlling the surface charge density of colloid particles can regulate their
      adsorption to the interface between two dielectrics.

PMID- 23534616
TI  - Non-invasive fibrosis biomarkers - APRI and Forns - are associated with liver
      stiffness in HIV-monoinfected patients receiving antiretroviral drugs.
AB  - BACKGROUND & AIMS: HIV-monoinfected patients are susceptible to liver injury by
      different factors and may develop liver fibrosis, which requires adequate
      clinical management in terms of therapy and disease monitoring. We aimed to
      evaluate the presence of liver fibrosis identified by transient elastography
      (TE), its relationships with indirect biochemical markers [the aspartate
      aminotransferase/platelet ratio index (APRI), the Forns index and FIB-4] and its
      predictive factors in HIV-monoinfected patients receiving antiretroviral therapy
      (ART). METHODS: Seventy-two HIV-monoinfected patients underwent TE and were
      evaluated using APRI, Forns and FIB-4. The clinical, immunological, virological
      and other biochemical characteristics were evaluated at the time of TE, together
      with their history of ART. RESULTS: Seven patients (10%) had liver stiffness (LS)
      values predicting cirrhosis, and 12 (17%) had values predicting significant or
      advanced fibrosis. Higher indirect biochemical scores of liver fibrosis were
      significantly associated with higher LS values [APRI rs  = 0.4296 (P < 0.001);
      Forns rs  = 0.4754 (P < 0.001); FIB-4 rs  = 0.285 (P = 0.015)]. At multivariable
      analysis, APRI (beta = 2.7405; P = 0.036), Forns (beta = 1.4174; P = 0.029) and
      triglyceride levels (beta = 1.3028; P = 0.007) were independently associated with
      LS. CONCLUSIONS: Indirect fibrosis biomarkers may increase the probability to
      detect liver injury enhancing a specific diagnostic workup and so contribute to
      improving the clinical management of HIV-monoinfected patients with clinically
      suspected liver disease.

PMID- 23534619
TI  - Communication: An efficient algorithm for evaluating the Breit and spin-spin
      coupling integrals.
AB  - We present an efficient algorithm for evaluating a class of two-electron
      integrals of the form r12?r12/r12(n) over one-electron Gaussian basis functions.
      The full Breit interaction in four-component relativistic theories beyond the
      Gaunt term is such an operator with n = 3. Another example is the direct spin
      spin coupling term in the quasi-relativistic Breit-Pauli Hamiltonian (n = 5).
      These integrals have been conventionally evaluated by expensive derivative
      techniques. Our algorithm is based on tailored Gaussian quadrature, similar to
      the Rys quadrature for electron repulsion integrals (ERIs), and can utilize the
      so-called horizontal recurrence relation to reduce the computational cost. The
      CPU time for computing all six Cartesian components of the Breit or spin-spin
      coupling integrals is found to be only 3 to 4 times that of the ERI evaluation.

PMID- 23534620
TI  - Communication: Solvation and dielectric response in ionic liquids--conductivity
      extension of the continuum model.
AB  - The solvation response of a polarity probe in a conducting liquid is analyzed
      based on simple continuum theory. A multi-exponential description of the dynamics
      is inverted to give an effective dc conductivity and a generalized permittivity
      spectrum in terms of Debye modes. For Coumarin 153 in ionic liquids the
      conductivity is found to be reduced systematically from the bulk value, whereas
      the permittivity from GHz-THz bulk absorption measurements is well reproduced by
      the solvation experiment. Thus, by using a dye as molecular antenna, the
      dielectric dispersion of the microscopic environment can be obtained.

PMID- 23534621
TI  - First-principles structural design of superhard materials.
AB  - We reported a developed methodology to design superhard materials for given
      chemical systems under external conditions (here, pressure). The new approach is
      based on the CALYPSO algorithm and requires only the chemical compositions to
      predict the hardness vs. energy map, from which the energetically preferable
      superhard structures are readily accessible. In contrast to the traditional
      ground state structure prediction method where the total energy was solely used
      as the fitness function, here we adopted hardness as the fitness function in
      combination with the first-principles calculation to construct the hardness vs.
      energy map by seeking a proper balance between hardness and energy for a better
      mechanical description of given chemical systems. To allow a universal
      calculation on the hardness for the predicted structure, we have improved the
      earlier hardness model based on bond strength by applying the Laplacian matrix to
      account for the highly anisotropic and molecular systems. We benchmarked our
      approach in typical superhard systems, such as elemental carbon, binary B-N, and
      ternary B-C-N compounds. Nearly all the experimentally known and most of the
      earlier theoretical superhard structures have been successfully reproduced. The
      results suggested that our approach is reliable and can be widely applied into
      design of new superhard materials.

PMID- 23534622
TI  - Microscopic theory of singlet exciton fission. I. General formulation.
AB  - Singlet fission, a spin-allowed energy transfer process generating two triplet
      excitons from one singlet exciton, has the potential to dramatically increase the
      efficiency of organic solar cells. However, the dynamical mechanism of this
      phenomenon is not fully understood and a complete, microscopic theory of singlet
      fission is lacking. In this work, we assemble the components of a comprehensive
      microscopic theory of singlet fission that connects excited state quantum
      chemistry calculations with finite-temperature quantum relaxation theory. We
      elaborate on the distinction between localized diabatic and delocalized exciton
      bases for the interpretation of singlet fission experiments in both the time and
      frequency domains. We discuss various approximations to the exact density matrix
      dynamics and propose Redfield theory as an ideal compromise between speed and
      accuracy for the detailed investigation of singlet fission in dimers, clusters,
      and crystals. Investigations of small model systems based on parameters typical
      of singlet fission demonstrate the numerical accuracy and practical utility of
      this approach.

PMID- 23534623
TI  - Microscopic theory of singlet exciton fission. II. Application to pentacene
      dimers and the role of superexchange.
AB  - We apply our theoretical formalism for singlet exciton fission, introduced in the
      previous paper [T. C. Berkelbach, M. S. Hybertsen, and D. R. Reichman, J. Chem.
      Phys. 138, 114102 (2013)] to molecular dimers of pentacene, a widely studied
      material that exhibits singlet fission in the crystal phase. We address a
      longstanding theoretical issue, namely whether singlet fission proceeds via two
      sequential electron transfer steps mediated by charge-transfer states or via a
      direct two-electron transfer process. We find evidence for a superexchange
      mediated mechanism, whereby the fission process proceeds through virtual charge
      transfer states which may be very high in energy. In particular, this mechanism
      predicts efficient singlet fission on the sub-picosecond timescale, in reasonable
      agreement with experiment. We investigate the role played by molecular vibrations
      in mediating relaxation and decoherence, finding that different physically
      reasonable forms for the bath relaxation function give similar results. We also
      examine the competing direct coupling mechanism and find it to yield fission
      rates slower in comparison with the superexchange mechanism for the dimer. We
      discuss implications for crystalline pentacene, including the limitations of the
      dimer model.

PMID- 23534624
TI  - A general method for spatially coarse-graining Metropolis Monte Carlo simulations
      onto a lattice.
AB  - A recently introduced method for coarse-graining standard continuous Metropolis
      Monte Carlo simulations of atomic or molecular fluids onto a rigid lattice of
      variable scale [X. Liu, W. D. Seider, and T. Sinno, Phys. Rev. E 86, 026708
      (2012)] is further analyzed and extended. The coarse-grained Metropolis Monte
      Carlo technique is demonstrated to be highly consistent with the underlying full
      resolution problem using a series of detailed comparisons, including vapor-liquid
      equilibrium phase envelopes and spatial density distributions for the Lennard
      Jones argon and simple point charge water models. In addition, the principal
      computational bottleneck associated with computing a coarse-grained interaction
      function for evolving particle positions on the discretized domain is addressed
      by the introduction of new closure approximations. In particular, it is shown
      that the coarse-grained potential, which is generally a function of temperature
      and coarse-graining level, can be computed at multiple temperatures and scales
      using a single set of free energy calculations. The computational performance of
      the method relative to standard Monte Carlo simulation is also discussed.

PMID- 23534625
TI  - Reorganization energy of electron transfer processes in ionic fluids: a molecular
      Debye-Huckel approach.
AB  - The reorganization energy of electron transfer processes in ionic fluids is
      studied under the linear response approximation using a molecule Debye-Huckel
      theory. Reorganization energies of some model reactants of electron transfer
      reactions in molten salts are obtained from molecular simulations and a molecule
      Debye-Huckel approach. Good agreements between simulation results and the results
      from our theoretical calculations using the same model Hamiltonian are found.
      Applications of our theory to electron transfer reactions in room temperature
      ionic liquids further demonstrate that our theoretical approach presents a
      reliable and accurate methodology for the estimation of reorganization energies
      of electron transfer reactions in ionic fluids.

PMID- 23534626
TI  - Multi-bit binary decoder based on Belousov-Zhabotinsky reaction.
AB  - It is known that Belousov-Zhabotinsky (BZ) reaction can be applied to chemical
      computation, e.g., image processing, computational geometry, logical computation,
      and so on. In the field of logical computation, some basic logic gates and basic
      combinational logic circuits, such as adder, counter, memory cell, have already
      been implemented in simulations or in chemical experiments. In this paper, we
      focus on another important combinational logic circuit, binary decoder.
      Integrating AND gate and NOT gate, we first design and implement a one-bit binary
      decoder through numerical simulation. Then we show that one-bit decoder can be
      extended to design two-bit, three-bit, or even higher bit binary decoders by a
      cascade method. The simulation results demonstrate the effectiveness of these
      devices. The chemical realization of decoders can guide the construction of more
      sophisticated functions based on BZ reaction; meanwhile, the cascade method can
      facilitate the design of other combinational logic circuits.

PMID- 23534627
TI  - Non-additivity of polarizabilities and van der Waals C6 coefficients of
      fullerenes.
AB  - We present frequency-dependent polarizabilities and C6 dipole-dipole dispersion
      coefficients for a wide range of fullerene molecules including C60, C70, C78,
      C80, C82, and C84. The static and dynamic polarizabilities at imaginary
      frequencies are computed using time-dependent Hartree-Fock, B3LYP, and CAM-B3LYP
      ab initio methods by employing the complex linear polarization propagator and are
      subsequently utilized to determine the C6 coefficients using the Casimir-Polder
      relation. Overall, the C60 and C70 average static polarizabilities alpha(0) agree
      to better than 2% with linear-response coupled-cluster single double and
      experimental benchmark results, and the C6 coefficient of C60 agrees to better
      than 1% with the best accepted value. B3LYP provides the best agreement with
      benchmark results with deviations less than 0.1% in alpha(0) and C6. We find that
      the static polarizabilities and the C6 coefficients are non-additive, and scale,
      respectively, as N(1.2) and N(2.2) with the number of carbon atoms in the
      fullerene molecule. The exponent for C6 power-dependence on N is much smaller
      than the value predicted recently based on a classical-metallic spherical-shell
      approximation of the fullerenes.

PMID- 23534628
TI  - Understanding cross-polarization (CP) NMR experiments through dipolar truncation.
AB  - A theoretical model based on the phenomenon of dipolar truncation is proposed to
      explain the nuances of polarization transfer from abundant to less-abundant
      nuclei in cross-polarization (CP) NMR experiments. Specifically, the transfer of
      polarization from protons to carbons (in solids) in strongly coupled systems is
      described in terms of effective Hamiltonians based on dipolar truncation. Through
      suitable model spin systems, the important role of dipolar truncation in the
      propagation of spin polarization in CP experiments is outlined. We believe that
      the analytic theory presented herein provides a convenient framework for modeling
      polarization transfer in strongly coupled systems.

PMID- 23534629
TI  - Tunneling, decoherence, and entanglement of two spins interacting with a
      dissipative bath.
AB  - We use numerically exact iterative path integral methods to investigate the
      decoherence and entanglement dynamics of a tunneling pair of two coupled qubits
      (spins) system interacting with a dissipative bath. We find that decoherence is
      generally accompanied by the destruction of entanglement, although the specifics
      of this destruction depend sensitively on the parameters of the Hamiltonian
      (qubit-qubit coupling and/or energy bias), the strength of dissipation, the
      temperature, and the choice of initial condition. We also observe that
      dissipation can in some cases generate a substantial amount of entanglement.
      Finally, if an entangled eigenstate exists which does not couple to the
      environment, the long-time entanglement can significantly exceed the value
      corresponding to the Boltzmann equilibrium state.

PMID- 23534630
TI  - Reconstructing equilibrium entropy and enthalpy profiles from non-equilibrium
      pulling.
AB  - The Jarzynski identity can be applied to instances when a microscopic system is
      pulled repeatedly but quickly along some coordinate, allowing the calculation of
      an equilibrium free energy profile along the pulling coordinate from a set of
      independent non-equilibrium trajectories. Using the formalism of Wiener
      stochastic path integrals in which we assign temperature-dependent weights to
      Langevin trajectories, we derive exact formulae for the temperature derivatives
      of the free energy profile. This leads naturally to analytical expressions for
      decomposing a free energy profile into equilibrium entropy and internal energy
      profiles from non-equilibrium pulling. This decomposition can be done from
      trajectories evolved at a unique temperature without repeating the measurement as
      done in finite-difference decompositions. Three distinct analytical expressions
      for the entropy-energy decomposition are derived: using a time-dependent
      generalization of the weighted histogram analysis method, a quasi-harmonic spring
      limit, and a Feynman-Kac formula. The three novel formulae of reconstructing the
      pair of entropy-energy profiles are exemplified by Langevin simulations of a two
      dimensional model system prototypical for force-induced biomolecular
      conformational changes. Connections to single-molecule experimental means to
      probe the functionals needed in the decomposition are suggested.

PMID- 23534631
TI  - Multidimensional direct free energy perturbation.
AB  - In this work we propose a multidimensional free energy perturbation scheme that
      allows the evaluation of the free energy difference between a state sampled based
      on importance sampling and almost any state that can be constructed by the
      reduction of the number of molecules in the system and the change of either the
      interaction energy or the thermodynamic state variable (e.g., the temperature) of
      the system. We show that via this approach it is possible to evaluate any
      thermodynamic property included but not limited to free energy, chemical
      potential, and pressure, along a series of isotherms from a single molecular
      simulation.

PMID- 23534632
TI  - Frequency-stepped acquisition in nuclear magnetic resonance spectroscopy under
      magic angle spinning.
AB  - The nuclear magnetic resonance of paramagnetic solids is usually characterized by
      the presence of large chemical shifts and shift anisotropies due to hyperfine
      interactions. Frequently the resulting spectra cover a frequency range of several
      megahertz, which is greater than the bandwidth of commercially available radio
      frequency (RF) probes, making it impossible to acquire the whole spectrum in a
      single experiment. In these cases it common to record a series of spectra, in
      which the probe is tuned to a different frequency for each, and then sum the
      results to give the "true" spectrum. While this method is very widely used on
      static samples, the application of frequency stepping under magic-angle spinning
      (MAS) is less common, owing to the increased complexity of the spin dynamics when
      describing the interplay of the RF irradiation with the mechanical rotation of
      the shift tensor. In this paper, we present a theoretical description, based on
      the jolting frame formalism of Caravatti et al. [J. Magn. Reson. 55, 88 (1983)],
      for describing the spin dynamics of a powder sample under MAS when subjected to a
      selective pulse of low RF-field amplitude. The formalism is used to describe the
      frequency stepping method under MAS, and under what circumstances the true
      spectrum is reproduced. We also present an experimental validation of the
      methodology under ultra-fast MAS with the paramagnetic materials LiMnPO4 and
      TbCsDPA.

PMID- 23534633
TI  - Ab initio study of the organic xenon insertion compound into ethylene and ethane.
AB  - This paper studies Xe-insertion ethylene and ethane compounds, i.e., HXeC2H3 and
      HXeC2H5. The structures, harmonic frequencies, and energetics for both molecules
      have been calculated at the MP2(full)/6-311++G(2d,2p) level. Our theoretical
      results predict the existence of HXeC2H3 and the instability of HXeC2H5. Natural
      bond orbital (NBO) analysis shows a strong ionic bond between the xenon atom and
      hydrocarbon radical. In addition, the interaction between the donor (Xe lone
      pair) and acceptor (the C-C antibonding orbital, i.e., pi*(C-C)) increases the
      stability of HXeC2H3.

PMID- 23534634
TI  - Decoupling of the copper core in a single copperphthalocyanine molecule.
AB  - Here, we show how a copper atom in a copperphthalocyanine (CuPc) molecule can be
      decoupled from its environment. This is realized by trapping the CuPc molecule
      between two adjacent nanowires that are 1.6 nm apart. Using low-temperature
      scanning tunnelling microscopy and spectroscopy, the structural and electronic
      properties of CuPc in the stable "molecular bridge" configuration have been
      studied. Constant current and differential conductivity maps are recorded to
      reveal the spatial variation of the electronic structure of the cores and the
      lobes of CuPc molecules. The core of CuPc molecule is dim at low voltages, but
      suddenly becomes bright at a voltage of 5 V. Time-resolved scanning tunnelling
      microscopy measurements show that some of the CuPc lobes are very stable, while
      other lobes are very dynamic.

PMID- 23534635
TI  - Phonon coupling of water monomers in a solid nitrogen matrix.
AB  - The infrared absorption spectra of the H2O, HDO, and D2O monomers isolated in
      solid N2 have been recorded at various temperatures between 4 and 30 K. A study
      of the absorption features of the nu1, nu2, and nu3 vibrational modes for each
      monomer shows their optical line shapes to be strongly temperature dependent. For
      all three modes, a decrease in the absorption amplitude and a proportional
      broadening of the linewidth was observed with increasing temperature, while the
      integrated absorbance remained constant. These observations were explained in
      terms of phonon coupling, by which high frequency intramolecular modes decay by
      exciting matrix phonons. Fits of the linewidth for the lowest frequency nu2
      vibrational mode to the predicted vibrational relaxation rate in a solid medium
      gave average phonon mode frequencies consistent with the Debye frequency for
      solid N2.

PMID- 23534636
TI  - Rotational spectroscopy of antipyretics: conformation, structure, and internal
      dynamics of phenazone.
AB  - The conformational and structural preferences of phenazone (antipyrine), the
      prototype of non-opioid pyrazolone antipyretics, have been probed in a supersonic
      jet expansion using rotational spectroscopy. The conformational landscape of the
      two-ring assembly was first explored computationally, but only a single conformer
      was predicted, with the N-phenyl and N-methyl groups on opposite sides of the
      pyrazolone ring. Consistently, the microwave spectrum evidenced a rotational
      signature arising from a single molecular structure. The spectrum exhibited very
      complicated fine and hyperfine patterns (not resolvable with any other
      spectroscopic technique) originated by the simultaneous coupling of the methyl
      group internal rotation and the spins of the two (14)N nuclei with the overall
      rotation. The internal rotation tunnelling was ascribed to the C-CH3 group and
      the barrier height established experimentally (7.13(10) kJ mol(-1)). The internal
      rotation of the N-CH3 group has a lower limit of 9.4 kJ mol(-1). The structure of
      the molecule was determined from the rotational parameters, with the phenyl group
      elevated ca. 25 degrees  with respect to the average plane of the pyrazolic
      moiety and a phenyl torsion of ca. 52 degrees . The origin of the conformational
      preferences is discussed in terms of the competition between intramolecular C
      H...N and C-H...O weak hydrogen bonds.

PMID- 23534637
TI  - Ground and excited states of vanadium hydroxide isomers and their cations,
      VOH(0,+) and HVO(0,+).
AB  - Employing correlation consistent basis sets of quadruple-zeta quality and
      applying both multireference configuration interaction and single-reference
      coupled cluster methodologies, we studied the electronic and geometrical
      structure of the [V,O,H](0,+) species. The electronic structure of HVO(0,+) is
      explained by considering a hydrogen atom approaching VO(0,+), while VOH(0,+)
      molecules are viewed in terms of the interaction of V(+,2+) with OH(-). The
      potential energy curves for H-VO(0,+) and V(0,+)-OH have been constructed as
      functions of the distance between the interacting subunits, and the potential
      energy curves have also been determined as functions of the H-V-O angle. For the
      stationary points that we have located, we report energies, geometries, harmonic
      frequencies, and dipole moments. We find that the most stable bent HVO(0,+)
      structure is lower in energy than any of the linear HVO(0,+) structures.
      Similarly, the most stable state of bent VOH is lower in energy than the linear
      structures, but linear VOH(+) is lower in energy than bent VOH(+). The global
      minimum on the potential energy surface for the neutral species is the X(3)A"
      state of bent HVO, although the X(5)A" state of bent VOH is less than 5 kcal/mol
      higher in energy. The global minimum on the potential surface for the cation is
      the X(4)Sigma(-) state of linear VOH(+), with bent VOH(+) and bent HVO(+) both
      more than 10 kcal/mol higher in energy. For the neutral species, the bent
      geometries exhibit significantly higher dipole moments than the linear
      structures.

PMID- 23534638
TI  - Spectroscopic study of the 2(2)Sigma+ and the 4(2)Sigma+ excited states of LiCa.
AB  - The 2(2)Sigma(+) and 4(2)Sigma(+) excited states of (7)Li(40)Ca have been studied
      by high resolution Fourier-transform spectroscopy. The data on the lower state,
      2(2)Sigma(+), were obtained by analyzing the rotationally resolved spectra of the
      thermal emission of LiCa in the 2(2)Sigma(+) -> X(2)Sigma(+) band around 9500 cm(
      1). These data contained transitions mainly from v' = 0 and 1 for N' up to 92 and
      allowed us to derive molecular parameters describing the potential curve of the
      state close to its minimum. The dataset on the second state, 4(2)Sigma(+), is
      much larger and comes from a laser-induced fluorescence experiment. The levels
      were excited by a single mode dye laser and the 4(2)Sigma(+) -> X(2)Sigma(+)
      fluorescence was recorded through a Fourier-transform spectrometer. For both
      states potential energy curves and Dunham coefficients were derived and the spin
      rotation structure was evaluated. The results are compared with theoretical and
      experimental data from the literature.

PMID- 23534639
TI  - Molecular structure of uranium carbides: isomers of UC3.
AB  - In this article, the most relevant isomers of uranium tricarbide are studied
      through quantum chemical methods. It is found that the most stable isomer has a
      fan geometry in which the uranium atom is bonded to a quasilinear C3 unit. Both,
      a rhombic and a ring CU(C2) structures are found about 104-125 kJ/mol higher in
      energy. Other possible isomers including linear geometries are located even
      higher. For each structure, we provide predictions for those molecular properties
      (vibrational frequencies, IR intensities, dipole moments) that could eventually
      help in their experimental detection. We also discuss the possible routes for the
      formation of the different UC3 isomers as well as the bonding situation by means
      of a topological analysis of the electron density.

PMID- 23534640
TI  - Ionization of Rydberg H2 molecules at doped silicon surfaces.
AB  - The present study focuses on the interaction of H2 Rydberg molecules with doped
      silicon semiconductor surfaces. Para-H2 Rydberg states with principal quantum
      numbers n = 17-21 and core rotational quantum number N(+) = 2 are populated via
      resonant two-colour two-photon (vacuum ultraviolet-ultraviolet) excitation and
      collide at grazing incidence with a surface. For small Rydberg-surface
      separation, the Rydberg states are ionized due to the attractive surface
      potential experienced by the Rydberg electron and the remaining ion-core is
      detectable by applying a sufficiently strong external electric field. It is found
      that the surface ionization profiles (ion signal vs applied field) of H2 on p
      type doped Si surfaces show a higher detected ion signal than for n-type Si
      surfaces, while an Au surface shows lower detected ion signal than either type of
      Si surface. It is shown that ion detectability decreases with increasing dopant
      density for both types of Si surfaces. Higher-n Rydberg states show higher ion
      detectability than lower-n Rydberg states but this variation becomes smaller when
      increasing the dopant density for both p- and n-type surfaces. Theoretical
      trajectory simulations were developed with a 2D surface potential model and using
      the over-the-barrier model for the ionization distance; the results help to
      explain the observed variations of the experimental surface ionization profiles
      with dopant density and type.

PMID- 23534641
TI  - Simulation studies of the Cl- + CH3I SN2 nucleophilic substitution reaction:
      comparison with ion imaging experiments.
AB  - In the previous work of Mikosch et al. [Science 319, 183 (2008)], ion imaging
      experiments were used to study the Cl(-) + CH3I -> ClCH3 + I(-) reaction at
      collision energies E(rel) of 0.39, 0.76, 1.07, and 1.9 eV. For the work reported
      here MP2(fc)/ECP/d direct dynamics simulations were performed to obtain an
      atomistic understanding of the experiments. There is good agreement with the
      experimental product energy and scattering angle distributions for the highest
      three E(rel), and at these energies 80% or more of the reaction is direct,
      primarily occurring by a rebound mechanism with backward scattering. At 0.76 eV
      there is a small indirect component, with isotropic scattering, involving
      formation of the pre- and post-reaction complexes. All of the reaction is direct
      at 1.07 eV. Increasing E(rel) to 1.9 eV opens up a new indirect pathway, the
      roundabout mechanism. The product energy is primarily partitioned into relative
      translation for the direct reactions, but to CH3Cl internal energy for the
      indirect reactions. The roundabout mechanism transfers substantial energy to
      CH3Cl rotation. At E(rel) = 0.39 eV both the experimental product energy
      partitioning and scattering are statistical, suggesting the reaction is primarily
      indirect with formation of the pre- and post-reaction complexes. However, neither
      MP2 nor BhandH/ECP/d simulations agree with experiment and, instead, give
      reaction dominated by direct processes as found for the higher collision
      energies. Decreasing the simulation E(rel) to 0.20 eV results in product energy
      partitioning and scattering which agree with the 0.39 eV experiment. The sharp
      transition from a dominant direct to indirect reaction as E(rel) is lowered from
      0.39 to 0.20 eV is striking. The lack of agreement between the simulations and
      experiment for E(rel) = 0.39 eV may result from a distribution of collision
      energies in the experiment and/or a shortcoming in both the MP2 and BhandH
      simulations. Increasing the reactant rotational temperature from 75 to 300 K for
      the 1.9 eV collisions, results in more rotational energy in the CH3Cl product and
      a larger fraction of roundabout trajectories. Even though a ClCH3-I(-) post
      reaction complex is not formed and the mechanistic dynamics are not statistical,
      the roundabout mechanism gives product energy partitioning in approximate
      agreement with phase space theory.

PMID- 23534642
TI  - Prediction of rock salt structure of (InN)32 nanoparticles from first principles
      calculations.
AB  - From first principles calculations, we show that (InN)32 nanoparticles favor rock
      salt structure compared with wurtzite structure in bulk. A phase transition from
      wurtzite to rock salt structure is known to occur in bulk InN at 12.1 GPa and
      higher values of pressure for AlN and GaN. However, at the nanoscale we show that
      this structural transition takes place in (InN)32 without applying pressure. The
      charge asymmetry value "g" and cation/anion size ratio in InN describe very well
      this behavior. Similar studies on nanoparticles of AlN and GaN as well as a few
      other binary compounds such as MgS, AgI, ZnO, and CdSe, however, do not show such
      a transition. Our results suggest (InN)32 to be a unique candidate as further
      calculations on a few larger size (InN)n nanoparticles show that a filled cage
      (two shells) (InN)12@(InN)48 structure of (InN)60 has higher binding energy
      compared with a rock salt structure of (InN)64 leading to the conclusion that
      other 3D structures are likely to become favorable over rock salt structure for
      larger sizes.

PMID- 23534643
TI  - Density and confinement effects of glass forming m-toluidine in nanoporous Vycor
      investigated by depolarized dynamic light scattering.
AB  - We investigate the reorientational dynamics of supercooled m-toluidine contained
      in a matrix of nanoporous Vycor with depolarized dynamic light scattering. Under
      equilibrium conditions a clear sample is obtained and the dynamics of m-toluidine
      molecules from inside the nanopores can be accessed via light scattering.
      However, when supercooling the imbibed liquid at conventional cooling rates,
      strong non-equilibrium effects occur due to the mismatch of expansion
      coefficients and the sample gets turbid several tens of Kelvin above the bulk
      glass transition. Only at cooling rates as low as 0.02 K/min this can be avoided
      and the dynamics of m-toluidine in confinement can be followed even below the
      bulk glass transition temperature. In confinement a pronounced acceleration of
      the reorientational dynamics is observed and the characteristic correlation times
      follow an Arrhenius law close to T(g). However it seems likely that part of the
      observed differences to bulk behavior is due to density effects, which are
      reduced but cannot be fully avoided at low cooling rates.

PMID- 23534644
TI  - Thermodynamic scaling and corresponding states for the self-diffusion coefficient
      of non-conformal soft-sphere fluids.
AB  - In this work, we explore transport properties of a special type of repulsive
      spheres that exhibit remarkable scaling of their thermodynamic properties. In
      order to accomplish that we propose a new way to derive and express effective
      hard-sphere diameters for transport properties of simple fluids. The procedure
      relies on mapping the system's transport properties, in the low density limit, to
      the hard-sphere fluid. We have chosen a set of soft-sphere systems characterised
      by a well-defined variation of their softness. These systems represent an
      extension of the repulsive Lennard-Jones potential widely used in statistical
      mechanics of fluids and are an accurate representation of the effective repulsive
      potentials of real systems. The self-diffusion coefficient of the soft-sphere
      fluids is obtained by equilibrium molecular dynamics. The soft-sphere collision
      integrals of different systems are shown to follow quite simple relationships
      between each other. These collision integrals are incorporated, through the
      definition of the effective hard-sphere diameter, in the resulting equation for
      the self-diffusion coefficient. The approach followed exhibits a density
      rescaling that leads to a single master curve for all systems and temperatures.
      The scaling is carried through to the level of the mean-squared displacement.

PMID- 23534645
TI  - Diffusion, thermal diffusion, and Soret coefficients and optical contrast factors
      of the binary mixtures of dodecane, isobutylbenzene, and 1,2,3,4
      tetrahydronaphthalene.
AB  - We have measured the Soret (S(T)), diffusion (D), and thermal diffusion (D(T))
      coefficients of the three binary benchmark mixtures of dodecane (C12),
      isobutylbenzene, and 1,2,3,4-tetrahydronaphthalene at T = 25 degrees C for at
      least five different concentrations each, covering the entire binary composition
      range. The two different optical techniques employed, optical beam deflection and
      optical digital interferometry, are in good to excellent agreement. Additionally,
      we have carefully measured the optical contrast factors (?n/?c)(p, T) and
      (?n/?T)(p, c). If the temperature and composition dependence of the mixture
      density is taken into account, both the Lorentz-Lorenz (LL) and the Looyenga (LO)
      equations give reasonable predictions of (?n/?c)(p, T). In case of (?n/?T)(p, c),
      only the LO equation yields good predictions in case of constant molecular
      polarizabilities alpha(i) of the pure compounds. If the apparent temperature
      dependence of alpha(i) is explicitly taken into account, excellent predictions
      are obtained both from the LL and the LO equations.

PMID- 23534646
TI  - Thermodynamic functions as correlation-function integrals.
AB  - Expressions of some thermodynamic functions as correlation-function integrals,
      such as the Ornstein-Zernike integral, the Kirkwood-Buff integrals, and the
      integral formulas for virial coefficients, are recalled. It is noted, as has been
      remarked before, that the choice of molecular centers from which intermolecular
      distances are measured is arbitrary and that different choices lead to different
      forms of the correlation functions but that the integrals must be independent of
      those choices. This is illustrated with the second virial coefficients of hard
      spheres in one, two, and three dimensions, with that of gaseous propane in three
      dimensions, and with computer simulations of the pair correlations in water and
      in a dilute aqueous solution of propane.

PMID- 23534647
TI  - Hydration forces between surfaces of surfactant coated single-walled carbon
      nanotubes.
AB  - The interaction force between functionalized single-walled carbon nanotubes
      (SWNTs) plays an important role in the fabrication of self-assembled and highly
      ordered SWNT arrays for a wide range of potential applications. Here, we measured
      interaction force between SWNTs encapsulated with polymerized surfactant
      monolayer (p-SWNTs). The balance between the repulsion between p-SWNTs and the
      osmotic pressure exerted by poly(ethylene glycol) in aqueous solution results in
      two-dimensional hexagonal arrays of p-SWNTs with very small surface to surface
      distances (<1 nm). The interaction force measured by the osmotic pressure
      technique shows characteristic decay length of hydration force in its origin.

PMID- 23534648
TI  - On the equivalence between specific adsorption and kinetic equation descriptions
      of the admittance response in electrolytic cells.
AB  - The response of an electrolytic cell, in the shape of a slab, is analyzed in the
      framework of the Poisson-Nernst-Planck model in the limit of full dissociation.
      Two different types of boundary conditions on the electrodes are compared. One
      type describes the exchange of charges between the volume and the external
      circuit, in the form originally proposed by Chang and Jaffe and later extended to
      include specific adsorption, where the surface current density is proportional to
      the variation of the surface bulk density of ions with respect to the value of
      equilibrium. The other one describes the surface adsorption, in the limit of
      Langmuir. We show that in the simple case where the ions dissolved in the
      insulating liquid are identical in all the aspects, except for the sign of the
      charge, the two models are equivalent only if the phenomenological parameter
      entering the boundary condition of the Chang-Jaffe model, kappa, is frequency
      dependent, and related to the adsorption coefficient, k(a), in the form kappa =
      iomegatau/(1 + iomegatau)k(a), where tau is the desorption time and omega the
      circular frequency of the applied voltage, as proposed long ago by Macdonald.

PMID- 23534649
TI  - Electric double layer force between charged surfaces: effect of solvent
      polarization.
AB  - In this paper, we develop a theory to delineate the consequences of finite
      solvent polarization in electric double layer interaction or the osmotic pressure
      between two similar or oppositely charged surfaces. We use previously published
      Langevin-Bikerman equations to calculate this electric double layer interaction
      force or the osmotic pressure between the charged surfaces. The osmotic pressure
      between oppositely charged surfaces is found to be much larger than that between
      similarly charged surfaces, and for either case, the influence of solvent
      polarization ensures a larger pressure than that predicted by the Poisson
      Boltzmann (PB) model. We derive distinct scaling relationships to explain the
      increase of the pressure as a function of the separation between the surfaces,
      the solvent polarizability, and the number density of water molecules. Most
      importantly, we demonstrate that our theory can successfully reproduce the
      experimental results of interaction force between similar and oppositely charged
      surfaces, by accounting for the large under-prediction made by the corresponding
      PB model.

PMID- 23534650
TI  - Photoinduced dynamics in a molecule metal nanoparticle complex: mean-field
      approximation versus exact treatment of the interaction.
AB  - Photoexcitation of a molecule placed in the proximity of a metal nanoparticle
      (MNP) is described theoretically. For a sufficient small spatial extension of the
      whole system the molecule-MNP coupling is given by the instantaneous Coulomb
      interaction. The coupling can also be considered in terms of a local field to
      which an external field has been transferred due to the presence of the MNP. It
      is known that such an approach can explain a number of observations. However, it
      fails to describe molecular excited state quenching. By considering the exact
      molecule-MNP Coulomb-coupling and a related mean field approximation which
      directly leads to a local field description we investigate this disappearance of
      excited state quenching in detail. Laser pulse induced dynamics in the molecule
      MNP system are studied and the importance of higher multipole excitations in a
      spherical MNP is underlined. The equivalence of the mean field approximation with
      the exact approach when calculating spectra of linear absorption is also
      demonstrated.

PMID- 23534651
TI  - Theoretical study on the tungsten-induced reduction of transition temperature and
      the degradation of optical properties for VO2.
AB  - We have studied the effect of the doped tungsten on the phase transition
      temperature and the optical properties between the monoclinic phase and the
      rutile phase of VO2 by performing first-principles calculations. It is found that
      the introduction of tungsten (W) significantly decreases the transition
      temperature between the rutile VO2 and the monoclinic VO2, with reducing the
      energy difference between the two phases. Meanwhile, our calculations indicate
      that the doped W lowers the infrared light transmittance of the monoclinic VO2,
      being consistent with the experimental observations. The nature about the
      reduction of the transition temperature and the change of the optical properties
      arising from the W dopants is revealed. Our results are valuable for application
      of VO2 as an optical energy material in future.

PMID- 23534652
TI  - The effect of fluctuations, thermal and otherwise, on the temperature dependence
      of thermopower in aromatic chain single-molecule junctions.
AB  - We report a theoretical study of the thermopower of single-molecule junctions
      with focus on phenyl-based molecular junctions. In contrast to prior studies,
      thermal fluctuations of the torsional angle between the phenyl rings and
      variations in the position of the molecular level alignment with respect to the
      electrode Fermi energy were taken into account. Full thermopower histograms were
      obtained, and their dependence on the magnitude of the fluctuations was studied.
      We found that at large molecular orbital variations, the thermopower becomes
      strongly dependent on the torsion angle and can even change sign. This results in
      a marked effect of fluctuations on the thermopower distribution, yielding an
      average thermopower at high temperatures that differs (smaller or larger) from
      the fluctuation-free value, depending on the strength of fluctuations. We
      therefore conclude that fluctuations should be taken into account both when
      extracting single-molecule parameters, such as the molecular level-Fermi level
      offset, and in predictions of the thermopower of molecular junctions.

PMID- 23534653
TI  - Molecular and electronic structure of electroactive self-assembled monolayers.
AB  - Self-assembled monolayers (SAMs) containing electroactive functional groups are
      excellent model systems for the formation of electronic devices by self-assembly.
      In particular ferrocene-terminated alkanethiol SAMs have been extensively studied
      in the past. However, there are still open questions related with their
      electronic structure including the influence of the ferrocene group in the SAM
      induced work function changes of the underlying metal. We have thus carried out a
      thorough experimental and theoretical investigation in order to determine the
      molecular and electronic structure of ferrocene-terminated alkanethiol SAMs on Au
      surfaces. In agreement with previous studies we found that the Fc-containing
      alkanethiol molecules adsorb forming a thiolate bond with the Au surface with a
      molecular geometry 30 degrees  tilted with respect to the surface normal.
      Measured surface coverages indicate the formation of a compact monolayer. We
      found for the first time that the ferrocene group has little influence on the
      observed work function decrease which is largely determined by the alkanethiol.
      Furthermore, the ferrocene moiety lies 14 A above the metal surface covalently
      bonded to the alkanethiol SAM and its HOMO is located at -1.6 eV below the Fermi
      level. Our results provide new valuable insight into the molecular and electronic
      structure of electroactive SAMs which are of fundamental importance in the field
      of molecular electronics.

PMID- 23534654
TI  - Interfaces of propylene carbonate.
AB  - Propylene carbonate (PC) wets graphite with a contact angle of 31 degrees  at
      ambient conditions. Molecular dynamics simulations agree with this contact angle
      after 40% reduction of the strength of graphite-C atom Lennard-Jones interactions
      with the solvent, relative to the models used initially. A simulated nano-scale
      PC droplet on graphite displays a pronounced layering tendency and an Aztex
      pyramid structure for the droplet. Extrapolation of the computed tensions of PC
      liquid-vapor interface estimates the critical temperature of PC accurately to
      about 3%. PC molecules lie flat on the PC liquid-vapor surface and tend to
      project the propyl carbon toward the vapor phase. For close PC neighbors in
      liquid PC, an important packing motif stacks carbonate planes with the outer
      oxygen of one molecule snuggled into the positively charged propyl end of another
      molecule so that neighboring molecule dipole moments are approximately
      antiparallel. The calculated thermal expansion coefficient and the dielectric
      constants for liquid PC agree well with experiment. The distribution of PC
      molecule binding energies is closely Gaussian. Evaluation of the density of the
      coexisting vapor then permits estimation of the packing contribution to the PC
      chemical potential and that contribution is about two thirds of the magnitude of
      the contributions due to attractive interactions, with opposite sign.

PMID- 23534655
TI  - Thermodynamics of iodide adsorption at the instantaneous air-water interface.
AB  - We performed molecular dynamics simulations using both polarizable and non
      polarizable force fields to study the adsorption of iodide to the air-water
      interface. A novel aspect of our analysis is that the progress of ion adsorption
      is measured as the distance from the instantaneous interface, which is defined by
      a coarse-graining scheme proposed recently by Willard and Chandler
      ["Instantaneous liquid interfaces," J. Phys. Chem. B 114, 1954-1958 (2010)].
      Referring structural and thermodynamic quantities to the instantaneous interface
      unmasks molecular-scale details that are obscured by thermal fluctuations when
      the same quantities are referred to an average measure of the position of the
      interface, such as the Gibbs dividing surface. Our results suggest that an ion
      adsorbed at the interface resides primarily in the topmost water layer, and the
      interfacial location of the ion is favored by enthalpy and opposed by entropy.

PMID- 23534656
TI  - Thermally activated intermixture in pentacene-perfluoropentacene
      heterostructures.
AB  - Using thermal desorption spectroscopy (TDS) the thermal stability of binary
      pentacene/perfluoropentacene (PEN/PFP) thin films has been investigated for
      various preparation protocols. Variation of stoichiometry ratio reveals a
      significantly enhanced thermal stability in comparison to the single compounds
      only for films with equimolar stoichiometry. The stabilization also depends on
      the preparation method and was found for co-deposition as well as for multi
      stacks and subsequently grown PEN/PFP-stacks but not for stacks grown in the
      reversed order. By systemically varying the substrate temperature during
      deposition, we prove that the resulting intermixture is caused by a thermally
      activated diffusion during film growth and not due to post-deposition diffusion
      induced upon heating during TDS measurements. The different extents of thermal
      stabilization are discussed in the context of the film morphology studied by
      means of atomic force microscopy (AFM). For complementary information, optical
      absorption spectra of the heterostructures are analyzed, where the arisal of new
      absorption bands and the extinction of excitonic bands existing in the pure
      compounds are identified as decisive criteria to judge the efficiency of
      intermixture.

PMID- 23534657
TI  - Molecular structure and elastic properties of thermotropic liquid crystals:
      integrated molecular dynamics--statistical mechanical theory vs molecular field
      approach.
AB  - The connection between the molecular structure of liquid crystals and their
      elastic properties, which control the director deformations relevant for electro
      optic applications, remains a challenging objective for theories and
      computations. Here, we compare two methods that have been proposed to this
      purpose, both characterized by a detailed molecular level description. One is an
      integrated molecular dynamics-statistical mechanical approach, where the bulk
      elastic constants of nematics are calculated from the direct correlation function
      (DCFs) and the single molecule orientational distribution function [D. A.
      McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is
      obtained from atomistic molecular dynamics trajectories, together with the radial
      distribution function, from which the DCF is then determined by solving the
      Ornstein-Zernike equation. The other approach is based on a molecular field
      theory, where the potential of mean torque experienced by a mesogen in the liquid
      crystal phase is parameterized according to its molecular surface. In this case,
      the calculation of elastic constants is combined with the Monte Carlo sampling of
      single molecule conformations. Using these different approaches, but the same
      description, at the level of molecular geometry and torsional potentials, we have
      investigated the elastic properties of the nematic phase of two typical mesogens,
      4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods
      yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in
      the average elastic constants and in their anisotropy. These are interpreted in
      terms of the different approximations and the different ways of accounting for
      the structural properties of molecules in the two approaches. In general, the
      results point to the role of the molecular shape, which is modulated by the
      conformational freedom and cannot be fully accounted for by a single descriptor
      such as the aspect ratio.

PMID- 23534658
TI  - Effect of size polydispersity on the crystal-fluid and crystal-glass transition
      in hard-core repulsive Yukawa systems.
AB  - We investigated the effect of size polydispersity on the crystal-fluid transition
      in hard-core repulsive Yukawa systems by means of Monte Carlo simulations for
      several state points in the Yukawa parameter space. Size polydispersity was
      introduced in the system only with respect to the hard particle cores; particles
      with different diameters had the same surface potential psi0, but the charge per
      particle was not varied with packing fraction or distance. We observed a shift to
      higher packing fraction of the crystal-fluid transition of bulk crystals with a
      fixed log-normal size distribution upon increasing the polydispersity, which was
      more pronounced for weakly charged particles (psi0 ~ 23 mV) compared to more
      highly charged particles (psi0 ~ 46 mV), and also more pronounced for larger
      Debye screening length. At high polydispersities (>=0.13) parts of the more
      highly charged systems that were initially crystalline became amorphous. The
      amorphous parts had a higher polydispersity than the crystalline parts,
      indicating the presence of a terminal polydispersity beyond which the homogeneous
      crystal phase was no longer stable.

PMID- 23534659
TI  - Laplacian spectra of recursive treelike small-world polymer networks: analytical
      solutions and applications.
AB  - A central issue in the study of polymer physics is to understand the relation
      between the geometrical properties of macromolecules and various dynamics, most
      of which are encoded in the Laplacian spectra of a related graph describing the
      macrostructural structure. In this paper, we introduce a family of treelike
      polymer networks with a parameter, which has the same size as the Vicsek fractals
      modeling regular hyperbranched polymers. We study some relevant properties of the
      networks and show that they have an exponentially decaying degree distribution
      and exhibit the small-world behavior. We then study the Laplacian eigenvalues and
      their corresponding eigenvectors of the networks under consideration, with both
      quantities being determined through the recursive relations deduced from the
      network structure. Using the obtained recursive relations we can find all the
      eigenvalues and eigenvectors for the networks with any size. Finally, as some
      applications, we use the eigenvalues to study analytically or semi-analytically
      three dynamical processes occurring in the networks, including random walks,
      relaxation dynamics in the framework of generalized Gaussian structure, as well
      as the fluorescence depolarization under quasiresonant energy transfer. Moreover,
      we compare the results with those corresponding to Vicsek fractals, and show that
      the dynamics differ greatly for the two network families, which thus enables us
      to distinguish between them.

PMID- 23534660
TI  - Self-assembled morphologies of ABA triblock copolymer brushes in selective
      solvents.
AB  - A simulated annealing method is used to investigate the self-assembled
      morphologies of symmetric ABA triblock copolymer brushes, formed by one end of
      the A-blocks tethered onto a planar surface, immersed in a solvent selective for
      the middle B-blocks. The morphological dependences of the brushes on polymer
      grafting density and block lengths are investigated systematically. Phase
      diagrams for systems with different grafting densities are constructed. The
      simulation results show that the grafted amphiphilic triblock copolymers can self
      assemble to form a variety of complicated morphologies which can be classified in
      terms of the number of A-rich layers in the morphology. In particular, the
      formation of the structures with one A-rich layer or called "folded" brush
      structures is consistent with the speculation from the experimental studies of
      ABA triblock copolymer brushes. More detailed structures depend on the grafting
      density and the lengths of the blocks. Furthermore, at a high grafting density,
      the effects of the lengths of blocks and the interaction energies between
      different species in the system on the conformation of chains are investigated to
      illustrate the formation mechanisms of self-assembled morphologies of the
      amphiphilic triblock copolymer brushes.

PMID- 23534661
TI  - Electrostatic free energy for a confined nanoscale object in a fluid.
AB  - We present numerical calculations of electrostatic free energies, based on the
      nonlinear Poisson-Boltzmann (PB) equation, for the case of an isolated spherical
      nano-object in an aqueous suspension, interacting with charged bounding walls. We
      focus on systems with a low concentration of monovalent ions (?10(-4) M), where
      the range of electrostatic interactions is long (~30 nm) and comparable to the
      system and object dimensions (~100 nm). Locally tailoring the geometry of the
      boundaries creates a modulation in the object-wall interaction, which for
      appropriately chosen system dimensions can be strong enough to result in stable
      spatial trapping of a nanoscale entity. A detailed view of the underlying
      mechanism of the trap shows that the physics depends predominantly on counterion
      entropy and the depth of the potential well is effectively independent of the
      object's dielectric function; we further note an appreciable trap depth even for
      an uncharged object in the fluid. These calculations not only provide a
      quantitative framework for understanding geometry-driven electrostatic effects at
      the nanoscale, but will also aid in identifying contributions from phenomena
      beyond mean field PB electrostatics, e.g., Casimir and other fluctuation-driven
      forces.

PMID- 23534662
TI  - Sedimentation equilibrium and the generalized Archimedes' principle.
AB  - The buoyancy concept is critically re-examined for applications to dispersions of
      nano-particles, such as colloids, proteins, or macromolecules. It is shown that
      when the size of the buoyant particle is not too different (say, at most a factor
      of ten) from the size of the dispersed particles, new intriguing phenomena
      emerge, leading to the violation of the Archimedes' principle. The resulting
      buoyancy force depends not only on the volume of the particle and on the mass
      density of the dispersion, but also on the relative size of the particles, on
      their geometry, and on the interactions between the buoyant particle and the
      fluid. Explicit expressions for such a generalized Archimedes' principle are
      obtained and the results are tested against targeted experiments in colloidal
      dispersions.

PMID- 23534663
TI  - Experimental and theoretical studies of scaling of sizes and intrinsic viscosity
      of hyperbranched chains in good solvents.
AB  - Using a set of hyperbranched polystyrenes with different overall molar masses but
      a uniform subchain length or a similar overall molar mass but different subchain
      lengths, we studied their sizes and hydrodynamic behaviors in toluene (a good
      solvent) at T = 25  degrees C by combining experimental (laser light scattering
      (LLS) and viscometry) and theoretical methods based on a partially permeable
      sphere model. Our results show that both the average radii of gyration (<R(g)>)
      and hydrodynamic radius (<R(h)>) are scaled to the weight-average molar mass
      (M(w)) as <R(g)> ~ <R(h)> ~ M(w)(gamma)M(w,s) (phi), with gamma = 0.47 +/- 0.01
      and phi = 0.10 +/- 0.01; and their intrinsic viscosity ([eta]) quantitatively
      follow the Mark-Houwink-Sakurada (MHS) equation as [eta] =
      K(eta)M(w)(nu)M(w,s)(MU) with K(eta) = 2.26 * 10(-5), nu = 0.39 +/- 0.01, and MU
      = 0.31 +/- 0.01, revealing that these model chains with long subchains are indeed
      fractal objects. Further, our theoretical and experimental results broadly agree
      with each other besides a slight deviation from the MHS equation for short
      subchains, similar to dendrimers, presumably due to the multi-body hydrodynamic
      interaction. Moreover, we also find that the average viscometric radius
      (<R(eta)>) determined from intrinsic viscosity is slightly smaller than <R(h)>
      measured in dynamic LLS and their ratio (<R(eta)>/<R(h)>) roughly remains 0.95 +/
      0.05, reflecting that linear polymer chains are more draining with a smaller
      <R(h)> than their hyperbranched counterparts for a given intrinsic viscosity. Our
      current study of the "defect-free" hyperbranched polymer chains offers a standard
      model for further theoretical investigation of hydrodynamic behaviors of
      hyperbranched polymers and other complicated architectures, in a remaining
      unexploited research field of polymer science.

PMID- 23534664
TI  - Ionic arrest of segmental motion and emergence of spatio-temporal heterogeneity:
      a fluorescence investigation of (polyethylene glycol + electrolyte) composites.
AB  - Temperature dependent steady state and time resolved fluorescence measurements
      have been performed to explore the interaction and dynamics in polymer
      electrolyte composite of the following general formula: [0.85 PEG + 0.15{f KNO3+
      (1-f) LiNO3}], with f denoting fraction of potassium ion in the 0.15 mol
      electrolyte present in the medium. Poly(ethylene glycol) with number-averaged
      molecular weight of 300 (PEG300) has been employed as polymer and C153 as the
      fluorescent probe. Substantial excitation wavelength dependence of probe
      fluorescence emission in presence of electrolyte suggests presence of spatial
      heterogeneity which vanishes either upon raising temperature or removing the
      electrolyte. This has been interpreted as arising from the cation-induced arrest
      of polymer segmental motion. Temporal heterogeneity in these composites is
      manifested via fractional viscosity dependence of average solvation and rotation
      rates of the dissolved probe. Viscosity decoupling of these rates in composites
      is found to depend on cation identity and is also reflected via the corresponding
      activation energies. The degree of decoupling differs between solvation and
      rotation, inducing an analogy to the observations made in deeply supercooled
      liquids. In addition, conformity to hydrodynamic predictions is recovered by
      measuring f dependent solute rotation at higher temperatures. Several
      complimentary but different experiments are suggested to re-examine the mechanism
      proposed here, based on the fluorescence results, for the emergence of spatio
      temporal heterogeneity in these composites and its disappearance either in the
      absence of any electrolyte or at higher temperatures.

PMID- 23534665
TI  - Solvation thermodynamics and heat capacity of polar and charged solutes in water.
AB  - The solvation thermodynamics and in particular the solvation heat capacity of
      polar and charged solutes in water is studied using atomistic molecular dynamics
      simulations. As ionic solutes we consider a F(-) and a Na(+) ion, as an example
      for a polar molecule with vanishing net charge we take a SPC/E water molecule.
      The partial charges of all three solutes are varied in a wide range by a scaling
      factor. Using a recently introduced method for the accurate determination of the
      solvation free energy of polar solutes, we determine the free energy, entropy,
      enthalpy, and heat capacity of the three different solutes as a function of
      temperature and partial solute charge. We find that the sum of the solvation heat
      capacities of the Na(+) and F(-) ions is negative, in agreement with experimental
      observations, but our results uncover a pronounced difference in the heat
      capacity between positively and negatively charged groups. While the solvation
      heat capacity DeltaC(p) stays positive and even increases slightly upon charging
      the Na(+) ion, it decreases upon charging the F(-) ion and becomes negative
      beyond an ion charge of q = -0.3e. On the other hand, the heat capacity of the
      overall charge-neutral polar solute derived from a SPC/E water molecule is
      positive for all charge scaling factors considered by us. This means that the
      heat capacity of a wide class of polar solutes with vanishing net charge is
      positive. The common ascription of negative heat capacities to polar chemical
      groups might arise from the neglect of non-additive interaction effects between
      polar and apolar groups. The reason behind this non-additivity is suggested to be
      related to the second solvation shell that significantly affects the solvation
      thermodynamics and due to its large spatial extent induces quite long-ranged
      interactions between solvated molecular parts and groups.

PMID- 23534666
TI  - Optimization of exciton currents in photosynthetic systems.
AB  - In an approach analogous to that used to treat electronic currents in
      semiconductor quantum dots, we investigate the exciton current in a pigment
      network that is sandwiched between two exciton reservoirs, also known as the
      emitter and the acceptor. Employing the master equation for the reduced density
      matrix, the exciton current is obtained analytically for a two-site model, and
      numerically for an eight-site Fenna-Matthews-Olson (FMO) subunit model. It is
      found that, to maximize the exciton current with a specific network
      configuration, there exist optimal emitter temperatures and exciton transfer
      rates between the network and the reservoirs. The steady state current in the FMO
      model is consistent with the trapping time calculated by network optimization in
      the one-exciton picture. The current optimization with respect to various control
      parameters is discussed for the FMO model. At and below the biologically relevant
      transfer rate 1 ps(-1), the FMO network is more efficient for excitation energy
      transfer than the two-site model. Beyond this scale, the FMO network shows
      robustness with respect to the interplay with the reservoirs.

PMID- 23534667
TI  - Theoretical study of interactions of BSA protein in a NaCl aqueous solution.
AB  - Bovine Serum Albumine (BSA) aqueous solutions in the presence of NaCl are
      investigated for different protein concentrations and low to intermediate ionic
      strengths. Protein interactions are modeled via a charge-screened colloidal
      model, in which the range of the potential is determined by the Debye-Huckel
      constant. We use Monte Carlo computer simulations to calculate the structure
      factor, and assume an oblate ellipsoidal form factor for BSA. The theoretical
      scattered intensities are found in good agreement with the experimental small
      angle X-ray scattering intensities available in the literature. The performance
      of well-known integral equation closures to the Ornstein-Zernike equation, namely
      the mean spherical approximation, the Percus-Yevick, and the hypernetted chain
      equations, is also assessed with respect to computer simulation.

PMID- 23534668
TI  - meta-Selective C-H bond alkylation with secondary alkyl halides.
AB  - Ruthenium catalysts enabled C-H bond functionalizations on arenes with
      challenging secondary alkyl halides. Particularly, ruthenium(II) biscarboxylate
      complexes proved to be the key to success for direct alkylations with excellent
      levels of unusual meta-selectivity. The direct alkylations occurred under mild
      reaction conditions with ample scope and tolerated valuable functional groups.
      Detailed mechanistic studies were performed, including various competition
      experiments as well as reactions with isotopically labeled substrates. These
      studies provided strong support for an initial reversible cyclometalation. The
      cycloruthenation thereby activates the arene for a subsequent remote
      electrophilic-type substitution with the secondary alkyl halides. Independently
      prepared cycloruthenated complexes were found to be catalytically active provided
      that a carboxylate ligand was present, thereby highlighting the key importance of
      carboxylate assistance for effective meta-selective C-H bond alkylations.

PMID- 23534669
TI  - Use of narrow mass-window, high-resolution extracted product ion chromatograms
      for the sensitive and selective identification of protein modifications.
AB  - Protein modifications, including oxidative modifications, glycosylations, and
      oxidized lipid-protein adducts, are becoming increasingly important as biomarkers
      and in understanding disease etiology. There has been a great deal of interest in
      mapping these on Apo B100 from low density lipoprotein (LDL). We have used
      extracted ion chromatograms of product ions generated using a very narrow mass
      window from high-resolution tandem mass spectrometric data collected on a rapid
      scanning quadrupole time-of-flight (QTOF) instrument, to selectively and
      sensitively detect modified peptides and identify the site and nature of a number
      of protein modifications in parallel. We have demonstrated the utility of this
      method by characterizing for the first time oxidized phospholipid adducts to LDL
      and human serum albumin and for the detection of glycosylation and kynurenin
      formation from the oxidation of tryptophan residues in LDL. 

PMID- 23534670
TI  - Early phrenic motor neuron loss and transient respiratory abnormalities after
      unilateral cervical spinal cord contusion.
AB  - Contusion-type cervical spinal cord injury (SCI) is one of the most common forms
      of SCI observed in patients. In particular, injuries targeting the C3-C5 region
      affect the pool of phrenic motor neurons (PhMNs) that innervates the diaphragm,
      resulting in significant and often chronic respiratory dysfunction. Using a
      previously described rat model of unilateral midcervical C4 contusion with the
      Infinite Horizon Impactor, we have characterized the early time course of PhMN
      degeneration and consequent respiratory deficits following injury, as this
      knowledge is important for designing relevant treatment strategies targeting
      protection and plasticity of PhMN circuitry. PhMN loss (48% of the ipsilateral
      pool) occurred almost entirely during the first 24 h post-injury, resulting in
      persistent phrenic nerve axonal degeneration and denervation at the diaphragm
      neuromuscular junction (NMJ). Reduced diaphragm compound muscle action potential
      amplitudes following phrenic nerve stimulation were observed as early as the
      first day post-injury (30% of pre-injury maximum amplitude), with slow functional
      improvement over time that was associated with partial reinnervation at the
      diaphragm NMJ. Consistent with ipsilateral diaphragmatic compromise, the injury
      resulted in rapid, yet only transient, changes in overall ventilatory parameters
      measured via whole-body plethysmography, including increased respiratory rate,
      decreased tidal volume, and decreased peak inspiratory flow. Despite significant
      ipsilateral PhMN loss, the respiratory system has the capacity to quickly
      compensate for partially impaired hemidiaphragm function, suggesting that C4
      hemicontusion in rats is a model of SCI that manifests subacute respiratory
      abnormalities. Collectively, these findings demonstrate significant and
      persistent diaphragm compromise in a clinically relevant model of midcervical
      contusion SCI; however, the therapeutic window for PhMN protection is restricted
      to early time points post-injury. On the contrary, preventing loss of innervation
      by PhMNs and/or inducing plasticity in spared PhMN axons at the diaphragm NMJ are
      relevant long-term targets.

PMID- 23534671
TI  - Factors affecting the Haemophilia Joint Health Score in children with severe
      haemophilia.
AB  - Joint damage from bleeding episodes leads to physical or functional limitations
      in people with haemophilia. Various factors may influence the frequency and
      severity of joint damage. This study examined whether age, prophylaxis, history
      of high-titre inhibitors (HTI) and bleeding events influenced the Haemophilia
      Joint Health Score (HJHS) in children. Medical and physiotherapy notes of boys
      with severe haemophilia, aged 4-18 years, were reviewed to identify factors
      associated with increased HJHS. The HJHS of 83 boys (median age: 11) ranged from
      0 to 25, with 44/83 (53%) having a score of zero. The median HJHS was 0 (mean
      2.6). In the non-HTI group, the HJHS for boys on late prophylaxis was 2.68 times
      higher than those who started early and the HJHS was on average 10% higher for
      every additional recent bleed. In this group the odds of having a zero score fell
      by 30% for every year increase in age. Boys with a history of HTI had higher HJHS
      scores than the non-HTI group, and age, number of recent bleeds and tolerized
      status were positively associated with HJHS. The score rose on average by 28% for
      every year of age and by 76% for non-tolerized boys. This study provides further
      evidence supporting early prophylaxis use and the importance of immune tolerance
      therapy. The HJHS is a useful tool for identifying and tracking changes in joint
      health with respect to therapy or disease progression. With improvements in
      haemophilia treatment, the disproportionate number of zero scores will continue
      to make interpretation of the HJHS challenging.

PMID- 23534672
TI  - Is breakfast skipping associated with physical activity among U.S. adolescents? A
      cross-sectional study of adolescents aged 12-19 years, National Health and
      Nutrition Examination Survey (NHANES).
AB  - OBJECTIVE: To examine the association between breakfast skipping and physical
      activity among US adolescents aged 12-19 years. DESIGN: A cross-sectional study
      of nationally representative 2007-2008 National Health and Nutrition Examination
      Survey (NHANES) data. SETTING: Breakfast skipping was assessed by two 24 h
      dietary recalls. Physical activity was self-reported by participants and
      classified based on meeting national recommendations for physical activity for
      the appropriate age group. Multiple logistic regression analysis was used to
      model the association between breakfast skipping and physical activity while
      controlling for confounders. SUBJECTS: A total of 936 adolescents aged 12-19
      years in the USA. RESULTS: After adjusting for family income, there was no
      association between breakfast skipping and meeting physical activity guidelines
      for age among adolescents aged 12-19 years (OR = 0.95, 95% CI 0.56, 1.32).
      CONCLUSIONS: Findings from the study differ from previous research findings on
      breakfast skipping and physical activity. Therefore, further research that uses
      large, nationally representative US samples and national recommended guidelines
      for physical activity is needed.

PMID- 23534673
TI  - Frey's syndrome: diagnosis in geriatric dentistry.
AB  - Frey's syndrome, is characterized by warmth, flushing and sweating of the face,
      most of time in the preauricular region, initiated by any gustatory stimulus. It
      is frequently related to parotid surgery. A case of Frey's syndrome in a 81-year
      old female whose long-delayed clinical onset post-parotidectomy is presented. 

PMID- 23534674
TI  - The value of second polar body detection 4 hours after insemination and early
      rescue ICSI in preventing complete fertilisation failure in patients with
      borderline semen.
AB  - In this study we evaluated the value of short-time insemination and early rescue
      intra-cytoplasmic sperm injection (ICSI) in preventing the occurrence of complete
      fertilisation failure for mild or moderate male infertility patients. A total of
      866 couples with borderline semen who underwent in vitro fertilisation treatment
      in 2010 were included. Regular insemination was performed between January and
      June of 2010 and short-term insemination was performed from July through December
      2010, where, as early as 4h after insemination, oocytes were denuded from cumulus
      cells and extrusion of the second polar body was evaluated. Of the 4153 mature
      oocytes with a detectable second polar body 4 h after insemination, 3874 (93.3%)
      showed signs of fertilisation on Day 1. Where no second polar body was present in
      any of the retrieved oocytes for a given patient, rescue ICSI was performed
      immediately. Similar rates of normal fertilisation and percentage of good-quality
      embryos were obtained between early rescue ICSI and regular ICSI. Clinical
      pregnancy occurred in 16 of 43 patients (37.2%) receiving early rescue ICSI. Our
      results showed early rescue ICSI in combination with evaluation of the second
      polar body 4 h following insemination is an effective method to prevent complete
      fertilisation failure for patients with mild or moderate male infertility.

PMID- 23534675
TI  - WNT-3A and WNT-5A counteract lipopolysaccharide-induced pro-inflammatory changes
      in mouse primary microglia.
AB  - Surveying microglia, the resident macrophage-like cells in the central nervous
      system, continuously screen their surroundings to sense imbalance in tissue
      homeostasis. Their activity is tightly regulated in both a pro- and anti
      inflammatory manner. We have previously shown that the lipoglycoproteins WNT-3A
      and WNT-5A drive pro-inflammatory transformation in primary mouse microglia
      cells, arguing that WNTs have a role in the modulation of the central nervous
      system immune response. In this study, we address the effects of recombinant WNT
      3A and WNT-5A on lipopolysaccharide (LPS)-activated mouse primary microglia to
      investigate the putative anti-inflammatory modulation of microglia by WNTs. While
      both WNT-3A and WNT-5A alone induce an up-regulation of cyclooxygenase 2 (COX2),
      a generic pro-inflammatory microglia marker, LPS exceeds these effects
      dramatically. However, combination of LPS and WNTs results in a dose-dependent
      decrease in LPS-induced cyclooxygenase 2 protein and mRNA expression. In
      conclusion, our data suggest that WNTs have a dual and context-dependent effect
      on microglia acting in a homeostatic pro- and anti-inflammatory manner.

PMID- 23534676
TI  - Establishing the ellipsoidal geometry of a benzoic acid-based amphiphile via
      dimer switching: insights from intramolecular rotation and facial H-bond torsion.
AB  - Soft molecular ellipsoids conceived from 3,4-di(dodecyloxy)benzoic acid (DDBA)
      amphiphile draw attention to monomer structure design, intramolecular -COOH
      headgroup twist (phi degrees ) and cyclic-acyclic dimer switching through facial
      H-bond torsion (psi degrees ). Generically, precipitation in hydrogen bonded
      systems has been the prime phenomenon once the critical aggregation
      concentrations were reached in the bulk solution. DDBA was no exception to this
      generalization. It formed precipitates in chloroform and methanol with no
      specific geometry but with cyclic dimer motifs in them. On the contrary, surface
      pressure modulated interfacial aggregation with ellipsoidal geometry followed
      acyclic dimerization (catemer motif) with various levels of headgroup torsion,
      established through real-time polarization modulated infrared reflection
      absorption spectroscopy (IRRAS) and density functional theory (DFT) calculations,
      that estimated the energy costs for these unexplored pathways. The reaction
      coordinates phi degrees  and psi degrees  in consonance with 2D surface pressure
      modulation thus directed the shape anisotropy during the dynamic self-assembly of
      DDBA. Changes in subphase pH and metal ionic environment had a derogatory effect
      on the ellipsoid formation, the structural requirement for which strictly
      followed a stringent need for twin alkyl chains in an asymmetric unit cell, as 4
      dodecyloxybenzoic acid (MABA) with a single alkyl chain formed exclusively
      spherical assemblies with no dimer modulation. The investigation thus reports
      unexplored energy pathways toward ellipsoidal geometry of the amphiphile in the
      course of its interfacial aggregation.

PMID- 23534677
TI  - Single crystal to single crystal transformation and hydrogen-atom transfer upon
      oxidation of a cerium coordination compound.
AB  - Trivalent and tetravalent cerium compounds of the octamethyltetraazaannulene
      (H2omtaa) ligand have been synthesized. Electrochemical analysis shows a strong
      thermodynamic preference for the formal cerium(IV) oxidation state. Oxidation of
      the cerium(III) congener Ce(Homtaa)(omtaa) occurs by hydrogen-atom transfer that
      includes a single crystal to single crystal transformation upon exposure to an
      ambient atmosphere.

PMID- 23534678
TI  - Microalbuminuria screening for detecting chronic kidney disease in the general
      population: a systematic review.
AB  - BACKGROUND: Microalbuminuria screening is widely used in high-risk populations
      but seldom used in the general population for detecting chronic kidney disease
      (CKD). Systematic reviews focused on screening for CKD are rare, and the issues
      about microalbuminuria screening in the general population have never been
      reviewed. We systematically reviewed studies regarding microalbuminuria screening
      and evaluated the benefits and harms of this screening method in the general
      population. METHODS: We systematically searched MEDLINE, PubMed, and the Cochrane
      Library for English articles published from January 1970 to 13 December 2011.
      Quality assessments were performed using the QUADAS tool or the Drummond's 10
      point checklist. Due to the high heterogeneity of the study designs, meta
      analysis for the study results was not possible. Therefore, we performed a
      narrative synthesis. RESULTS: Six articles from four studies made up our final
      study population, with four articles evaluating different screening methodologies
      and two reporting cost-effectiveness analyses. The qualities of the included
      articles ranged from fair to high. Spot urine albumin concentration and spot
      urine albumin:creatinine ratio had a similar diagnostic performance for
      microalbuminuria screening in the general population. Screening for
      microalbuminuria in high-risk populations, such as patients with diabetes,
      hypertension, or old age, was cost-effective. However, there was no consensus
      regarding the cost-effectiveness for microalbuminuria screening in the general
      population. CONCLUSIONS: Microalbuminuria screening in high-risk populations is
      cost-effective. However, the cost-effectiveness of screening for microalbuminuria
      in the general population deserves further study. To keep costs low, spot urine
      albumin concentration may be preferable than the albumin:creatinine ratio.

PMID- 23534679
TI  - The adolescent relational dialectic and the peer roots of adult social
      functioning.
AB  - The long-term import of a fundamental challenge of adolescent social development
      establishing oneself as a desirable peer companion while avoiding problematic
      behaviors often supported within peer groups-was examined in a community sample
      of 184 adolescents, followed from ages 13 to 23, along with parents, peers, and
      romantic partners. The dialectical nature of this challenge appeared in findings
      that autonomy vis-a-vis peer influences predicted both long-term success avoiding
      problematic behavior but also more difficulty establishing strong adult
      friendships. Conversely, being a desirable peer companion in adolescence
      predicted more positive adult relationships but also greater alcohol use.
      Adolescents who established themselves as both desirable companions and as
      autonomous vis-a-vis peers were rated as most successful by their parents at age
      23. 

PMID- 23534680
TI  - Deconstructing crop processes and models via identities.
AB  - This paper is part review and part opinion piece; it has three parts of
      increasing novelty and speculation in approach. The first presents an overview of
      how some of the major crop simulation models approach the issue of simulating the
      responses of crops to changing climatic and weather variables, mainly atmospheric
      CO2 concentration and increased and/or varying temperatures. It illustrates an
      important principle in models of a single cause having alternative effects and
      vice versa. The second part suggests some features, mostly missing in current
      crop models, that need to be included in the future, focussing on extreme events
      such as high temperature or extreme drought. The final opinion part is
      speculative but novel. It describes an approach to deconstruct resource use
      efficiencies into their constituent identities or elements based on the Kaya
      Porter identity, each of which can be examined for responses to climate and
      climatic change. We give no promise that the final part is 'correct', but we hope
      it can be a stimulation to thought, hypothesis and experiment, and perhaps a new
      modelling approach. 

PMID- 23534681
TI  - Impact of preformulation on drug development.
AB  - INTRODUCTION: Preformulation assists scientists in screening lead candidates
      based on their physicochemical and biopharmaceutical properties. This data is
      useful for selection of new chemical entities (NCEs) for preclinical
      efficacy/toxicity studies which is a major section under investigational new drug
      application. A strong collaboration between discovery and formulation group is
      essential for selecting right NCEs in order to reduce attrition rate in the late
      stage development. AREAS COVERED: This article describes the significance of
      preformulation research in drug discovery and development. Various crucial
      preformulation parameters with case studies have been discussed. EXPERT OPINION:
      Physicochemical and biopharmaceutical characterization of NCEs is a decisive
      parameter during product development. Early prediction of these properties helps
      in selecting suitable physical form (salt, polymorph, etc.) of the candidate.
      Based on pharmacokinetic and efficacy/toxicity studies, suitable formulation for
      Phase I clinical studies can be developed. Overall these activities contribute in
      streamlining efficacy/toxicology evaluation, allowing pharmacologically effective
      and developable molecules to reach the clinic and eventually to the market. In
      this review, the magnitude of understanding preformulation properties of NCEs and
      their utility in product development has been elaborated with case studies.

PMID- 23534682
TI  - End points in functional bowel disease.

PMID- 23534683
TI  - Short- and long-term impact of body mass index on laparoscopic rectal cancer
      surgery.
AB  - AIM: Obesity is associated with increased technical difficulty in laparoscopic
      surgery. However, its impact has been measured mainly for colectomy but not
      specifically for rectal excision. The aim of the study was to assess the impact
      of body mass index (BMI) on technical feasibility and oncological outcome of
      laparoscopic rectal excision for cancer. METHOD: A total of 490 patients treated
      by laparoscopic rectal excision for rectal cancer from January 1999 to June 2010
      were included. Seventy per cent had had preoperative radiochemotherapy. Patients
      were separated into four groups according to BMI (kg/m(2) ): < 20, 20-25, 25-30
      and >= 30. The impact of BMI on conversion, surgical morbidity, quality of
      excision (Quirke mesorectal grade and circumferential resection margin) and long
      term oncological outcome was determined. RESULTS: Among the 490 patients BMI was
      < 20 in 43, 20-25 in 223, 25-30 in 177 and >= 30 in 47. Mortality (overall 1%)
      and morbidity (overall 19%) were similar between the groups. Conversion in the
      four groups was 5%, 14%, 23% and 32% (P = 0.001). The quality of mesorectal
      excision and circumferential margins did not differ between the groups. The 5
      year local recurrence rates (0%, 4.6%, 5.3% and 5.9% respectively; P = 0.823) and
      the overall and disease-free survival were not significantly influenced by BMI.
      CONCLUSION: In laparoscopic surgery for rectal cancer, BMI influenced the risk of
      conversion but not surgical morbidity, quality of surgery and survival. This
      suggests that all patients, including obese patients, are suitable for
      laparoscopic surgery.

PMID- 23534689
TI  - Replacement of infected aortic prosthetic graft with aortic homograft after heart
      transplantation: 13-year follow-up.
AB  - Acute ascending aortic dissection (AAAD) is a rare complication after orthotopic
      heart transplantation. We report a patient with AAAD after heart transplantation
      in whom repair was complicated by infection of the ascending aortic prosthetic
      graft. This was successfully managed by re-do replacement with two cryopreserved
      aortic homografts. Despite extensive calcification in the wall, the homografts
      show no aneurysm or dilation after 10 years.

PMID- 23534690
TI  - Use of clomipramine as chemotherapy of the chronic phase of Chagas disease.
AB  - Chagas infection is a major endemic disease affecting Latin American countries.
      The persistence of Trypanosoma cruzi generates a chronic inflammatory reactivity
      that induces an immune response directed to the host's tissues. The effectiveness
      of the treatment in the chronic phase is still unsatisfactory due, amongst other
      reasons, to the collateral effects of the drugs used. We investigated the effect
      of clomipramine, a tricyclic antidepressant that, when used as a treatment of T.
      cruzi-chronically infected mice, inhibits trypanothione reductase, an exclusive
      and vital enzyme of T. cruzi. Clomipramine improved survival (P<0.05) by
      diminishing the parasite intensity as demonstrated by PCR studies in the heart
      and skeletal muscle, and significantly prevented the evolution to fibrosis of the
      inflammatory infiltrates. Clomipramine could be a good candidate for the
      treatment of chronic Chagas disease.

PMID- 23534692
TI  - Atomically precise gold nanoclusters as new model catalysts.
AB  - Many industrial catalysts involve nanoscale metal particles (typically 1-100 nm),
      and understanding their behavior at the molecular level is a major goal in
      heterogeneous catalyst research. However, conventional nanocatalysts have a
      nonuniform particle size distribution, while catalytic activity of nanoparticles
      is size dependent. This makes it difficult to relate the observed catalytic
      performance, which represents the average of all particle sizes, to the structure
      and intrinsic properties of individual catalyst particles. To overcome this
      obstacle, catalysts with well-defined particle size are highly desirable. In
      recent years, researchers have made remarkable advances in solution-phase
      synthesis of atomically precise nanoclusters, notably thiolate-protected gold
      nanoclusters. Such nanoclusters are composed of a precise number of metal atoms
      (n) and of ligands (m), denoted as Aun(SR)m, with n ranging up to a few hundred
      atoms (equivalent size up to 2-3 nm). These protected nanoclusters are well
      defined to the atomic level (i.e., to the point of molecular purity), rather than
      defined based on size as in conventional nanoparticle synthesis. The Aun(SR)m
      nanoclusters are particularly robust under ambient or thermal conditions (<200 
      degrees C). In this Account, we introduce Aun(SR)m nanoclusters as a new,
      promising class of model catalyst. Research on the catalytic application of
      Aun(SR)m nanoclusters is still in its infancy, but we use Au25(SR)18 as an
      example to illustrate the promising catalytic properties of Aun(SR)m
      nanoclusters. Compared with conventional metallic nanoparticle catalysts,
      Aun(SR)m nanoclusters possess several distinct features. First of all, while gold
      nanoparticles typically adopt a face-centered cubic (fcc) structure, Aun(SR)m
      nanoclusters (<2 nm) tend to adopt different atom-packing structures; for
      example, Au25(SR)18 (1 nm metal core, Au atomic center to center distance) has an
      icosahedral structure. Secondly, their ultrasmall size induces strong electron
      energy quantization, as opposed to the continuous conduction band in metallic
      gold nanoparticles or bulk gold. Thus, nanoclusters become semiconductors and
      possess a sizable bandgap (e.g., ~1.3 eV for Au25(SR)18). In addition, Aun(SR)m
      can be doped with a single atom of other metals, which is of great interest for
      catalysis, because the catalytic properties of nanoclusters can be truly tuned on
      an atom-by-atom basis. Overall, atomically precise Aun(SR)m nanoclusters are
      expected to become a promising class of model catalysts. These well-defined
      nanoclusters will provide new opportunities for achieving fundamental
      understanding of metal nanocatalysis, such as insight into size dependence and
      deep understanding of molecular activation, active centers, and catalytic
      mechanisms through correlation of behavior with the structures of nanoclusters.
      Future research on atomically precise nanocluster catalysts will contribute to
      the fundamental understanding of catalysis and to the new design of highly
      selective catalysts for specific chemical processes.

PMID- 23534691
TI  - Future directions for research on the development and prevention of early conduct
      problems.
AB  - This article describes our state of knowledge regarding the development and
      prevention of conduct problems in early childhood, then identifies directions
      that would benefit future basic and applied research. Our understanding about the
      course and risk factors associated with early-developing conduct problems has
      been significantly enhanced during the past three decades; however, many
      challenges remain in understanding the development of early conduct problems for
      girls, the contribution of poverty across variations in community urbanicity, and
      developing cascading models of conduct problems that incorporate prenatal risk.
      Significant advances in early prevention and intervention are also described, as
      well as challenges for identifying and engaging parents of at-risk children in
      nontraditional community settings.

PMID- 23534693
TI  - Oxidative responses induced by pharmacologic vitreolysis and/or long-term
      hyperoxia treatment in rat lenses.
AB  - PURPOSE: The aim of the study was to investigate the protective effects of intact
      vitreous gel on the lens after pharmacologic vitreolysis and hyperoxia exposure
      in rats in vivo. METHODS: Eyes of Sprague-Dawley rats were induced to posterior
      vitreous detachment (PVD) by pharmacologic vitreolysis, and the rats with and
      without PVD were treated with hyperoxia 3 h per day for 5 months. Lens
      transparency was monitored by a slit-lamp biomicroscope. A series of biochemical
      measurements were made in extracts of the lens cortex and nucleus. Ascorbate
      levels were measured in the aqueous and vitreous humors. RESULTS: No significant
      differences in lens transparency or morphology were observed in all groups, and
      no significant biochemical changes were observed in the cortex or nucleus of
      lenses of the PVD group. In the lens nucleus, the values of water-soluble protein
      concentration in PVD + hyperoxia group were lower than that of the PVD group. The
      levels of water-soluble proteins, glutathione (GSH) and ascorbate decreased in
      the hyperoxia group with an intact vitreous body. Vitreolysis enhanced the effect
      of hyperoxia, decreasing soluble protein, GSH and ascorbate below the levels seen
      in eyes with vitreolysis alone. The levels of antioxidants and soluble proteins
      were lower in the lens nucleus, and the effects of vitreolysis plus hyperoxia
      were more significant in the nucleus. Hyperoxia and hyperoxia plus vitreolysis
      reduced catalase activity and increased oxidized GSH to a greater extent in the
      lens cortex, although these treatments increased protein-GSH mixed disulfides in
      both regions. Long-term hyperoxia also lowered ascorbate levels in the vitreous
      and aqueous humors, an effect that was enhanced by vitreolysis. CONCLUSIONS:
      Exposure to excess molecular oxygen produces significant oxidative damage to the
      lens, especially the lens nucleus. These effects were enhanced by pharmacologic
      vitreolysis, indicating that intact vitreous gel protects the lens from oxidative
      damage.

PMID- 23534694
TI  - Rescue of cAMP response element-binding protein signaling reversed spatial memory
      retention impairments induced by subanesthetic dose of propofol.
AB  - AIMS: The intravenous anesthetic propofol caused episodic memory impairments in
      human. We hypothesized propofol caused episodic-like spatial memory retention but
      not acquisition impairments in rats and rescuing cAMP response element-binding
      protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV)
      inhibitor rolipram reversed these effects. METHODS: Male Sprague-Dawley rats were
      randomized into four groups: control; propofol (25 mg/kg, intraperitoneal);
      rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before
      propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were
      evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze
      (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h
      after propofol injection. Visible MWM training was simultaneously performed to
      resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min,
      and 24 h after propofol administration. RESULTS: Rolipram did not change propofol
      induced anesthetic/sedative states or impair motor skills. No difference was
      found on the latency to the platform during the visible MWM. Propofol impaired
      spatial memory retention but not acquisition. Rolipram reversed propofol-induced
      spatial memory impairments and suppression on cAMP levels, CaMKIIalpha and CREB
      phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein
      expression. CONCLUSIONS: Propofol caused spatial memory retention impairments but
      not acquisition inability possibly by inhibiting CREB signaling.

PMID- 23534695
TI  - Electrohydrodynamic bubbling: an alternative route to fabricate porous structures
      of silk fibroin based materials.
AB  - Conventional fabrication techniques and structures employed in the design of silk
      fibroin (SF) based porous materials provide only limited control over pore size
      and require several processing stages. In this study, it is shown that, by
      utilizing electrohydrodynamic bubbling, not only can new hollow spherical
      structures of SF be formed in a single step by means of bubbles, but the
      resulting bubbles can serve as pore generators when dehydrated. The bubble
      characteristics can be controlled through simple adjustments to the processing
      parameters. Bubbles with diameters in the range of 240-1000 MUm were fabricated
      in controlled fashion. FT-IR characterization confirmed that the rate of air
      infused during processing enhanced beta-sheet packing in SF at higher flow rates.
      Dynamic mechanical analysis also demonstrated a correlation between air flow rate
      and film tensile strength. Results indicate that electrohydrodynamically
      generated SF and their composite bubbles can be employed as new tools to generate
      porous structures in a controlled manner with a range of potential applications
      in biocoatings and tissue engineering scaffolds.

PMID- 23534696
TI  - Systematic review and meta-analysis of pharmacological therapies for painful
      diabetic peripheral neuropathy.
AB  - BACKGROUND: Painful diabetic peripheral neuropathy (pDPN) is prevalent among
      persons with diabetes and increases over time. Published guidelines recommend a
      number of medications to treat this condition providing clinicians with a variety
      of treatment options. This study provides a comprehensive systematic review and
      meta-analysis of published pharmacologic therapies for pDPN. METHODS: The
      published literature was systematically searched to identify randomized,
      controlled trials of all available pharmacologic treatments for pDPN (recommended
      or nonrecommended) reporting predefined efficacy and safety outcomes. Bayesian
      fixed-effect mixed treatment comparison methods were used to assess relative
      therapeutic efficacy and harms. RESULTS: Data from 58 studies including 29
      interventions and 11,883 patients were analyzed. Pain reduction over that of
      placebo on the 11-point numeric rating scale ranged from -3.29 for sodium
      valproate (95% credible interval [CrI] = [-4.21, -2.36]) to 1.67 for Sativex (
      0.47, 0.60). Estimates for most treatments were clustered between 0 and -1.5 and
      were associated with more study data and smaller CrIs. Pregabalin (>= 300 mg/day)
      was the most effective on the 100-point visual analog scale (-21.88; [-27.06, 
      16.68]); topiramate was the least (-3.09; [-3.99, -2.18]). Relative risks (RRs)
      of 30% pain reduction ranged from 0.78 (Sativex) to 1.84 (lidocaine 5% plaster).
      Analysis of the RR ratio of these 2 treatments reveals marginal significance for
      Sativex (3.27; [1.07, 9.81]), indicating the best treatment is only slightly
      better than the worst. Relative risks of 50% pain reduction ranged from 0.98
      (0.56, 1.52) (amitriptyline) to 2.25 (1.51, 3.00) (alpha-lipoic acid). RR ratio
      for these treatments was not statistically different (3.39; [0.88, 3.34]).
      Fluoxetine had the lowest risk of adverse events (0.94; [0.62, 1.23]); oxycodone
      had the highest (1.55; [1.45, 1.64]). Discontinuation RRs were clustered around
      0.8 to 1.5, with those on the extreme having greater uncertainty. CONCLUSIONS:
      Selecting an appropriate pDPN therapy is key given the large number of available
      treatments. Comparative results revealed relative equivalence among many of the
      studied interventions having the largest overall sample sizes and highlight the
      importance of standardization of methods to effectively assess pain.

PMID- 23534697
TI  - Pain experiences and self-management strategies among middle-aged and older
      adults with arthritis.
AB  - AIMS AND OBJECTIVES: The purposes were (1) to explore pain experiences and the
      use and perceived effectiveness of pain self-management methods among middle-aged
      and older adults with osteoarthritis or rheumatoid arthritis in mainland China
      and (2) to compare those with diagnoses of osteoarthritis and rheumatoid
      arthritis. BACKGROUND: Prior research has suggested that pain is a major concern
      for people with arthritis. However, studies systematically investigating pain
      experiences and self-management status of arthritis patients are scarce in
      mainland China. DESIGN: Descriptive survey. METHODS: Participants (n = 197) aged
      45 and over, diagnosed with either osteoarthritis or rheumatoid arthritis, and
      experiencing persistent pain were administered three self-report questionnaires:
      the Demographic Data Questionnaire, the Brief Pain Inventory and the Pain
      Management Inventory. RESULTS: The mean of the overall pain intensity was 5.6 (SD
      = 1.3). The median of number of pain sites was 7.0 (QR = 7.0) and the overall
      pain interference was 6.0 (QR = 2.6). Most participants experienced moderate to
      severe pain and interference. The current methods used for managing pain were
      perceived as only moderately effective. The sample used a median of 4.0 (QR =
      3.0) self-management methods. Most often used were prescribed medicine, massage,
      heat and activity pacing. Methods perceived as most helpful included prescribed
      medicine, over-the-counter medicine, hot baths and heat. Persons with rheumatoid
      arthritis had significantly more pain sites, higher pain intensity and greater
      number of pain management methods used compared to those with osteoarthritis.
      CONCLUSIONS: Pain management is a significant problem in this population. The
      findings highlight the importance of helping the individual to identify and
      appropriately use a variety of self-management methods, selecting the appropriate
      method(s) at any one time. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers
      are urged to develop appropriate interventions on pain management tailored to
      arthritis patients in mainland China.

PMID- 23534698
TI  - High-throughput optimization of Ir-catalyzed C-H borylation: a tutorial for
      practical applications.
AB  - With the aid of high-throughput screening, the efficiency of Ir-catalyzed C-H
      borylations has been assessed as functions of precatalyst, boron reagent, ligand,
      order of addition, temperature, solvent, and substrate. This study not only
      validated some accepted practices but also uncovered unconventional conditions
      that were key to substrate performance. We anticipate that insights drawn from
      these findings will be used to design reaction conditions for substrates whose
      borylations are difficult to impossible using standard catalytic conditions.

PMID- 23534699
TI  - Foam-film-stabilized liquid bridge networks in evaporative lithography and wet
      granular matter.
AB  - Evaporative lithography using latex particle templates is a novel approach for
      the self-assembly of suspension-dispersed nanoparticles into ordered microwire
      networks. The phenomenon that drives the self-assembly process is the propagation
      of a network of interconnected liquid bridges between the template particles and
      the underlying substrate. With the aid of video microscopy, we demonstrate that
      these liquid bridges are in fact the border zone between the underlying substrate
      and foam films vertical to the substrate, which are formed during the evaporation
      of the liquid from the suspension. The stability of the foam films and thus the
      liquid bridge network stability are due to the presence of a small amount of
      surfactant in the evaporating solution. We show that the same type of foam-film
      stabilized liquid bridge network can also propagate in 3D clusters of spherical
      particles, which has important implications for the understanding of wet granular
      matter.

PMID- 23534700
TI  - Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the
      CSTA gene encoding cystatin A.
AB  - Acral peeling skin syndrome (APSS) is a clinically and genetically heterogeneous
      disorder. We used whole-exome sequencing to identify the molecular basis of APSS
      in a consanguineous Jordanian-American pedigree. We identified a homozygous
      nonsense mutation (p.Lys22X) in the CSTA gene, encoding cystatin A, that was
      confirmed using Sanger sequencing. Cystatin A is a protease inhibitor found in
      the cornified cell envelope, and loss-of-function mutations have previously been
      reported in two cases of exfoliative ichthyosis. Our study expands the molecular
      pathology of APSS and demonstrates the value of next-generation sequencing in the
      genetic characterization of inherited skin diseases. 

PMID- 23534701
TI  - Long-term in vivo imaging of viscoelastic properties of the mouse brain after
      controlled cortical impact.
AB  - Traumatic brain injury (TBI) presents a variety of causes and symptoms, thus
      making the development of reliable diagnostic methods and therapeutic treatments
      challenging. Magnetic resonance elastography (MRE) is a technique that allows for
      a noninvasive assessment of the mechanical properties of soft biological tissue,
      such as tissue stiffness, storage modulus, and loss modulus. Importantly, by
      quantifying the changes in the stiffness of tissue that is often associated with
      disease, MRE is able to detect tissue pathologies at early stages. Recent
      improvements in instrumentation have allowed for the investigation of small
      samples with microscopic resolution (MUMRE). We hypothesize that MUMRE can
      sensitively detect variations in micromechanical properties in the brain caused
      by the compressive and shearing forces sustained during TBI. To test this
      hypothesis, we randomized 13 C57BL mice to receive a controlled cortical impact
      at a 0.5 mm or 0.75 mm depth, with both sham and naive mice as controls. Our
      objective was to propagate mechanical shear waves throughout the brain for in
      vivo TBI MUMRE imaging. The mechanical properties of the injured brain tissue
      were determined at days 0, 1, 7, and 28 post-injury. For both groups, we observed
      a significant drop in the stiffness of the impacted region immediately following
      the injury; the 0.75 mm animals experienced increased tissue softness that lasted
      longer than that for the 0.5 mm group. Although the shear stiffness, storage
      modulus, and loss modulus parameters all followed the same trend, the tissue
      stiffness yielded the most statistically significant results. Overall, this
      article introduces a transformative technique for mechanically mapping the brain
      and detecting brain diseases and injury.

PMID- 23534702
TI  - Cervi cornus Colla (deer antler glue) induce epidermal differentiation in the
      reconstruction of skin equivalents.
AB  - In the reconstruction of skin equivalents (SEs), keratinocyte differentiation is
      important because epidermal differentiation is closely related with barrier
      function. The aim of this study was to investigate the effects of Cervi cornus
      Colla (CCC) on the stem cell activity and epidermal differentiation in the
      reconstruction of skin equivalent. Four different models were constructed
      according to different composition of dermal substitute. Results showed similar
      morphologic findings when hyaluronic acid (HA) and/or CCC was added. But,
      immunohistochemical staining showed that p63 was significantly increased by
      addition of HA and/or CCC. Increased staining of integrin alpha6 and beta1 was
      variably observed when HA and/or CCC was added to make dermal substitute. These
      finding showed that addition of HA and/or CCC may affect the stem cell activity
      in the reconstruction of skin. Furthermore, filaggrin expression was much
      increased when CCC was added. It showed that epidermal differentiation was
      significantly improved by addition of CCC. In conclusion, simultaneous presence
      of HA and CCC contributed to the stem cell activity and epidermal differentiation
      in the reconstruction of SE. Legislation in the EU prohibits marketing cosmetics
      and personal care products that contain constituents that have been examined
      through animal experiments. To avoid these limitations, SEs can be used for
      testing the safety or the efficacy of cosmetic ingredients. Therefore, our
      results showed that combined use of HA and CCC can be helpful for the
      reconstruction of SE with good stem cell activity and epidermal differentiation.

PMID- 23534703
TI  - Two-dimensional Penning ionization electron spectroscopy of open-shell
      metallocenes: outer valence ionic states of vanadocene and nickelocene.
AB  - In order to investigate outer valence ionic states of open-shell metallocenes, we
      have applied two-dimensional collision-energy/electron-energy-resolved Penning
      ionization electron spectroscopy (2D-PIES) upon collision with metastable
      He*(2(3)S) excited atoms as well as a high level ab initio molecular orbital
      calculation (the partial third-order quasiparticle theory of the electron
      propagator (P3)) to ionization from neutral ground states of vanadocene ((4)A2g)
      and nickelocene ((3)A2g). Assignments of observed Penning ionization electron/He
      I ultraviolet photoelectron spectra were consistent with the P3 calculation
      results for ionization of alpha and beta spin electrons except for electron
      correlation bands observed by PIES. Negative collision energy dependence of
      partial Penning ionization cross-sections (CEDPICS) indicate attractive
      interaction with He*(2(3)S) around the molecule. Results by model potential
      calculation utilizing Li(2(2)S) instead of He*(2(3)S) for interaction between
      He*(2(3)S) and open-shell metallocenes do not explain the strong negative CEDPICS
      of the bands observed in PIES.

PMID- 23534704
TI  - Influence of isoflavone intake and equol-producing intestinal flora on prostate
      cancer risk.
AB  - BACKGROUND: The age-adjusted incidence rate of prostate cancer (PCa) has been
      reported to be lower among Asians than Western populations. A traditional
      Japanese meal, high in soybean products or isoflavones, may be associated with a
      decreased risk of PCa. Equol, which is converted from daidzein by human
      intestinal flora, is biologically more active than any other isoflavone aglycone.
      MATERIALS AND METHODS: We reviewed not only recent epidemiological studies on
      association of isoflavones with PCa risk, but also recent research on human
      intestinal bacteria responsible for converting daidzein into equol. Studies were
      systematically searched from the database published within the last 5 years of
      from 2008-2012. RESULTS: Five out of 6 articles showed significant association of
      isoflavones with a decreased risk of PCa, and two of them consistently showed
      that equol-producers carry a significantly reduced risk of PCa. Furthermore, 5
      human intestinal bacteria that can convert daidzein into equol were identified in
      the last 5 years. CONCLUSIONS: If equol can reduce risk of PCa, a possible
      strategy for reducing the risk of PCa may be to increase the proportion of equol
      producers by changing the intestinal flora to carrying an equol-producing
      bacterium with dietary alteration or probiotic technology.

PMID- 23534705
TI  - Lung cancer knowledge among secondary school male teachers in Kudat, Sabah,
      Malaysia.
AB  - BACKGROUND: The objective of this study is to determine knowledge about lung
      cancer among secondary school male teachers in Kudat, Sabah, Malaysia. MATERIALS
      AND METHODS: A cross-sectional study was conducted among three secondary schools
      located in Kudat district, Sabah, Malaysia during the period from June until
      September 2012. The protocol of this study was approved by ethics committee of
      Management and Science University, Malaysia. The aims were explained and a
      consent form was signed by each participant. Respondents were chosen randomly
      from each school with the help of the headmasters. Self-administrated
      questionnaires, covering socio-demographic characteristics and general knowledge
      of lung cancer, were distributed. Once all 150 respondents completed the
      questionnaire, they passed it to their head master for collecting and recording.
      All the data were analyzed using Statistical Package for the Social Sciences
      (SPSS) version 13. ANOVA and t-test were applied for univariate analysis; and
      multiple linear regression for multivariate analysis. RESULTS: A total of 150
      male secondary school teachers participated in this study. Their mean age was
      35.6 ? 6.5 (SD); maximum 50 and minimum 23 years old. More than half of the
      participants were Malay and married (52%, 79%; respectively). Regarding the
      knowledge about lung cancer, 57.3% of the participants mentioned that only males
      are affected by lung cancer. Some 70.7% mentioned that lung cancer can be
      transmitted from one person to another. More than half (56.7%) reported that lung
      cancer is not the leading cause of death in Malaysian males. As for risk factors,
      the majority reported that family history of lung cancer is not involved.
      However, 91.3% were aware that cigarettes are the main risk factor of lung cancer
      and more than half (52%) believed that second-hand smoking is one of the risk
      factor of lung cancer. More than half (51.3%) were not aware that asbestos,
      ionizing radiation and other cancer causing substances are risk factors for lung
      cancer. Quitting smoking, avoiding second-hand smoking and avoiding unnecessary x
      ray image of the chest (53.3%, 96.0%, 87.3%; respectively) are the main
      preventive measures mentioned by the participants. For the factors that influence
      the participants knowledge, univariate and multivariate analysis showed that only
      race was significant. CONCLUSIONS: Overall, the knowledge of school male teachers
      about lung cancer was low. However, few items were scored high: cigarettes are
      the main risk factor; avoiding second-hand smoking; and avoiding x-rays.
      Interventions to increase lung cancer awareness are needed to improve early
      detection behavior. Increase the price of pack of cigarettes to RM 20 and banning
      smoking in public places such as restaurants are highly recommended as primary
      preventive measures.

PMID- 23534706
TI  - Area-to-Area Poisson Kriging analysis of mapping of county- level esophageal
      cancer incidence rates in Iran.
AB  - BACKGROUND: Esophagus cancer, the third most common gastrointestinal cancer
      overall, demonstrates high incidence in parts of Iran. The counties of Iran vary
      in size, shape and population size. The aim of this study was to account for
      spatial support with Area-to-Area (ATA) Poisson Kriging to increase precision of
      parameter estimates and yield correct variance and create maps of disease rates.
      MATERIALS AND METHODS: This study involved application/ecology methodology,
      illustrated using esophagus cancer data recorded by the Ministry of Health and
      Medical Education (in the Non-infectious Diseases Management Center) of Iran. The
      analysis focused on the 336 counties over the years 2003-2007. ATA was used for
      estimating the parameters of the map with SpaceStat and ArcGIS9.3 software for
      analysing the data and drawing maps. RESULTS: Northern counties of Iran have high
      risk estimation. The ATA Poisson Kriging approach yielded variance increase in
      large sparsely populated counties. So, central counties had the most prediction
      variance. CONCLUSIONS: The ATAPoisson kriging approach is recommended for
      estimating parameters of disease mapping since this method accounts for spatial
      support and patterns in irregular spatial areas. The results demonstrate that the
      counties in provinces Ardebil, Mazandaran and Kordestan have higher risk than
      other counties.

PMID- 23534707
TI  - Finding genes discriminating smokers from non-smokers by applying a growing self
      organizing clustering method to large airway epithelium cell microarray data.
AB  - BACKGROUND: Cigarette smoking is the major risk factor for development of lung
      cancer. Identification of effects of tobacco on airway gene expression may
      provide insight into the causes. This research aimed to compare gene expression
      of large airway epithelium cells in normal smokers (n=13) and non-smokers (n=9)
      in order to find genes which discriminate the two groups and assess cigarette
      smoking effects on large airway epithelium cells. MATERIALS AND METHODS: Genes
      discriminating smokers from non-smokers were identified by applying a neural
      network clustering method, growing self-organizing maps (GSOM), to microarray
      data according to class discrimination scores. An index was computed based on
      differentiation between each mean of gene expression in the two groups. This
      clustering approach provided the possibility of comparing thousands of genes
      simultaneously. RESULTS: The applied approach compared the mean of 7,129 genes in
      smokers and non-smokers simultaneously and classified the genes of large airway
      epithelium cells which had differently expressed in smokers comparing with non
      smokers. Seven genes were identified which had the highest different expression
      in smokers compared with the non-smokers group: NQO1, H19, ALDH3A1, AKR1C1,
      ABHD2, GPX2 and ADH7. Most (NQO1, ALDH3A1, AKR1C1, H19 and GPX2) are known to be
      clinically notable in lung cancer studies. Furthermore, statistical discriminate
      analysis showed that these genes could classify samples in smokers and non
      smokers correctly with 100% accuracy. With the performed GSOM map, other nodes
      with high average discriminate scores included genes with alterations strongly
      related to the lung cancer such as AKR1C3, CYP1B1, UCHL1 and AKR1B10.
      CONCLUSIONS: This clustering by comparing expression of thousands of genes at the
      same time revealed alteration in normal smokers. Most of the identified genes
      were strongly relevant to lung cancer in the existing literature. The genes may
      be utilized to identify smokers with increased risk for lung cancer. A large
      sample study is now recommended to determine relations between the genes ABHD2
      and ADH7 and smoking.

PMID- 23534708
TI  - Knowledge of risk factors and early detection methods and practices towards
      breast cancer among nurses in Indira Gandhi Medical College, Shimla, Himachal
      Pradesh, India.
AB  - BACKGROUND: Breast cancer is an increasing health problem in India. Screening for
      early detection should lead to a reduction in mortality from the disease. It is
      known that motivation by nurses influences uptake of screening methods by women.
      This study aimed to investigate knowledge of breast cancer risk factors and early
      detection methods and the practice of screening among nurses in Indira Gandhi
      Medical College, Shimla, Himachal Pradesh. MATERIALS AND METHODS: A cross
      sectional study was conducted using a self-administered questionnaire to assess
      the knowledge of breast cancer risk factors, early detection methods and practice
      of screening methods among 457 nurses working in an Indira Gandhi Medical
      College, Shimla-H.P. Chi square test, Data was analysed using SPSS version 16.
      Test of significance used was chi square test. RESULTS: The response rate of the
      study was 94.9%. The average knowledge of risk factors about breast cancer of the
      entire population is 49%. 10.5% of nurses had poor knowledge, 25.2% of the nurses
      had good knowledge, 45% had very good knowledge and 16.3% of the nurses had
      excellent knowledge about risk factors of breast cancer and early detection
      methods. The knowledge level was significantly higher among BSC nurses than
      nurses with Diploma. 54% of participants in this study reportedly practice BSE at
      least once every year. Less than one-third reported that they had CBE within the
      past one year. 7% ever had mammogram before this study. CONCLUSIONS: Results from
      this study suggest the frequent continuing medical education programmes on breast
      cancer at institutional level is desirable.

PMID- 23534709
TI  - Significance of HPV infection and genic mutation of APC and K-ras in patients
      with rectal cancer.
AB  - BACKGROUND: Significance of HPV infection and genic mutation of APC and K-ras in
      rectal cancer has been investigated but not clarified. The objective of our study
      was to investigate these parameters in patients with rectal cancer to analyze
      correlations with biological behaviour, to determine relationships among the
      three, and also to demonstrate survival prognosis effects. METHODS: From December
      2007 to September 2008, 75 rectal cancer cases confirmed by histopathology in the
      Tumor Hospital of Xinjiang Medical University were enrolled. The control group
      consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm
      distant from the carcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras
      were detected by PCR and PCR-SSCP. All results were analyzed in relation to
      clinical pathological material, using chi-square and correlation analysis via
      SPSS.13 and Fisher's Exact Probability via STATA. 9.0. All 75 patients were
      followed up for survival analysis using Kaplan-Meier and Log-rank tests. RESULTS:
      55 out of 75 cases demonstrated gene HPV L1 while it was not detected in normal
      rectal mucosa tissue. HPV infection was correlated with age and lymphatic
      metastasis (P<0.05) but not other characteristics, such as ethnicity, tumor size,
      histological type, tumor type, Duke's stage and infiltration depth. Some 43 cases
      exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation (45.3%). APC
      genic mutation was correlated with gender( P<0.05), but not age, histological
      type, infiltration depth, lymphatic metastasis and Duke's stage. In 55 cases of
      rectal cancer with HPV infection, there were 31 cases with genic mutation of APC
      (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases of rectal
      cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%),
      respectively, with no significant relation. Survival analysis showed no
      statistical significance for K-ras genic mutation, APC genic mutation or HPV
      infection (P>0.05). However, the survival time of the patients with HPV infection
      was a little shorter than in cases without HPV infection. CONCLUSIONS: Our
      results suggest that HPV infection might be an important factor to bring about
      malignant phenotype of rectal cancer and influence prognosis. Genic mutation of
      APC and K-ras might be common early molecular events of rectal cancer, but
      without prognostic effects on medium-term or early stage patients with rectal
      cancer.

PMID- 23534710
TI  - Effect of MUC1 siRNA on drug resistance of gastric cancer cells to trastuzumab.
AB  - Trastuzumab is the first molecular targeting drug to increase the overall
      survival rate in advanced gastric cancer. However, it has also been found that a
      high intrinsic or primary trastuzumab resistance exists in some proportion of
      gastric cancer patients. In order to explore the mechanism of resistance to
      trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin
      1) in gastric cancer cells and its relationship with drug-resistance. Then using
      gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The
      results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA
      and protein expression of MUC1 being significantly upregulated. After
      transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was
      significantly reduced. Compared with the junk transfection and blank control
      groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was
      significantly increased. These results imply that HER2-positive gastric cancer
      cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by
      silencing expression of the MUC1 gene.

PMID- 23534711
TI  - Ovarian transposition for stage Ib squamous cell cervical cancer - lack of
      effects on survival rates?
AB  - BACKGROUND: To investigate the impact of ovarian transposition (OT) on survival
      rates of the patients with stage Ib squamous cell cervical cancer. MATERIALS AND
      METHODS: Ninety-two subjects who underwent a radical hysterectomy including
      oophorectomy were evaluated. For nineteen (20.7%) , OT was performed. Patients
      were divided into two groups, OT versus oophorectomy alone. The primary end-point
      of this study was to investigate the impact of OT on tumor recurrence rate and
      time, 5-year disease-free survival (DFS) and overall survival (OS) . These
      comparisons were performed for subgroups including patients who received
      radiotherapy versus who did not. Statistical analyses were conducted using the
      Chi-square test, T-test and Mann-Whitney test. OS was examined using the Kaplan
      Meier method. P <= 0.05 was considered to be statistically significant. RESULTS:
      The median follow-up period was 89 months for OT and 81 months for the
      oophorectomy group (p>0.05). Both groups experienced similar recurrence rates
      (31.6% vs. 26.4%, p=0.181). The median duration from surgery to recurrence, and
      surgery to death were also similar between the groups (p>0.05). The 5-year DFS
      and OS rates were both 68.4% for the OT group, and 73.6% and 77.8% for the
      oophorectomy group (p=0.457 and p=0.307, respectively). While the 5-year DFS rate
      was not statistically significant between the OT and oophorectomy groups who did
      not receive radiotherapy (p=0.148), the 5-year OS rate was significantly higher
      in the oophorectomy group (95.4% vs 66.7%, respectively) without radiotherapy
      (p=0.05). The 5-year DFS and OS rates were statistically similar between the
      groups who received adjuvant radiotherapy (p>0.05). CONCLUSIONS: Ovarian
      transposition has not significantly negative effect on the survival rates when
      adjuvant radiotherapy will be applied, while 5-year OS may be less in OT group if
      radiotherapy is not mandatory.

PMID- 23534712
TI  - Screening of microRNA in patients with esophageal cancer at same tumor node
      metastasis stage with different prognoses.
AB  - Patients at the same pathological stage of esophageal cancer (EC) that received
      the same surgical therapy by the same surgeon may have distinct prognoses. The
      current study aimed to explore the possibility of differentially- expressed
      microRNAs (miRNAs) underlying this phenomenon. Samples were collected from EC
      patients at the same tumor node metastasis (TNM) stage but with different
      prognoses. Paracancerous normal tissues were taken as controls. The specimens
      were histopathologically analyzed. Differentially-expressed miRNAs were analyzed
      using real-time quantitative reverse transcription polymerase chain reaction.
      Compared with patients with poor prognosis, those with good prognosis exhibited
      88 two-fold or more than two-fold increased miRNA fragments and 4 half-decreased
      miRNAs. The most noticeably up-regulated miRNAs included hsa-miR-31, hsa-miR-
      196b, hsa-miR-652, hsa-miR-125a-5p, hsa-miR-146b, hsa-miR-200c, hsa-miR-23b, hsa
      miR-29a, hsa-miR-186, hsa-miR-205, hsa-miR-376a, hsa-miR-410, hsa-miR-532-3p, and
      hsa-miR-598, whereas the most significantly- downregulated miRNAs were hsa-let
      7e, hsa-miR-130b, and hsa-miR-103. EC patients at same TNM stage but with
      different prognoses show differentially-expressed miRNAs.

PMID- 23534713
TI  - Common variations of DNA repair genes are associated with response to platinum
      based chemotherapy in NSCLCs.
AB  - AIM: Individual differences in chemosensitivity and clinical outcome of non-small
      cell lung cancer (NSCLC) patients may be induced by host inherited factors. We
      investigated the impact of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD
      Lys751Gln gene polymorphisms on the efficacy of platinum-based chemotherapy in
      NSCLC patients. METHODS: A total of 496 were consecutively selected from the
      Affiliated Hospital of Nantong University between Jan. 2003 and Nov. 2006, and
      all patients were followed-up until Nov. 2011. The genotyping of XPD Arg156Arg,
      XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln was conducted by duplex polymerase
      chain-reaction with the confronting-two-pair primer methods. RESULTS: Individuals
      with XPD 312 C/T+T/T and XPD 711 C/T+T/T exhibited poor responses to chemotherapy
      when compared with the wild- type genotype, with adjusted ORs(95% CI) of
      0.67(0.38-0.97) and 0.54(0.35-0.96), respectively. Cox regression showed the
      median PFS and OS of patients of XPD 312 C/T+T/T genotype and XPD 711 C/T+T/T
      genotype to be significantly lower than those with wild-type homozygous genotype.
      CONCLUSION: We found polymorphisms in XPD to be associated with response to
      platinum-based chemotherapy in NSCLC, and our findings provide information for
      therapeutic decisions for individualized therapy.

PMID- 23534714
TI  - Comparison of psychological influence on breast cancer patients between breast
      conserving surgery and modified radical mastectomy.
AB  - OBJECTIVE: To compare the influence of breast-conserving surgery (BCS) and
      modified radical mastectomy (MRM) on the psychological state of breast cancer
      patients. METHODS: Patients receiving MRM or BCS, and fulfilling the study
      criteria, were recruited. Patients were required to complete a self-reporting
      inventory (SCL- 90) on admission and 6 months after surgery and a self-rating
      depression scale (SDS) when discharged from hospital and 6 months after surgery.
      RESULTS: A total of 70 patients received MRM and 50 BCS. Compared with the
      national standard, patients suffered to some extent psychological problems on
      admission, at discharge from hospital and at 6 months after surgery. Patients
      received BCS had a higher score of SDS compared with those with MRM when
      discharged from hospital. However, 6 months after surgery, SDS score increased in
      MRM and decreased in the BCS group, so the difference was significant.
      CONCLUSION: The short-term psychological state of patients receiving BCS is worse
      than that with MRM but superior to MRM 6 months postoperatively. BCS imposed less
      influence on long term psychological state of breast cancer patients compared
      with MRM.

PMID- 23534715
TI  - c-KIT positive schistosomal urinary bladder carcinoma are frequent but lack KIT
      gene mutations.
AB  - Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms
      in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium
      (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor
      and implicated in the development of a number of human malignancies, has not been
      studied so far in schistosomal urinary bladder SCCs. We therefore determined
      immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120
      radical cystectomies of SCCs originally obtained from the Pathology Department of
      Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining
      intensity where the staining extent of >10% of cells was considered positive. c
      KIT overexpression was detected in 78.3% (94/120) of the patients, the staining
      extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%)
      respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and
      strong intensity respectively. Patients with positive bilharzial ova had
      significantly higher c-KIT expression than patients without (95.2% vs. 38.9%,
      P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive
      cases. The high rate of positivity in SBSCC was one of the striking findings;
      However, CD117 may be a potential target for site specific immunotherapy to
      improve the outcome of this tumor.

PMID- 23534716
TI  - Communication competencies of oncology nurses in Malaysia.
AB  - This paper reports on part of a large study to identify competencies of oncology
      nurses in Malaysia. It focuses on oncology nurses' communications-related
      competency. As an important cancer care team member, oncology nurses need to
      communicate effectively with cancer patients. Literature shows that poor
      communication can make patients feel anxious, uncertain and generally not
      satisfied with their nurses' care. This paper deliberates on the importance of
      effective communication by oncology nurses in the context of a public hospital.
      Four focus group discussions were used in this study with 17 oncology/cancer care
      nurses from Malaysian public hospitals. The main inclusion criterion was that the
      nurses had to have undergone a post-basic course in oncology, or have work
      experience as a cancer care nurse. The findings indicated that nurses do
      communicate with their patients, patients' families and doctors to provide
      information about the disease, cancer treatment, disease recurrence and side
      effects. Nurses should have good communication skills in order to build
      relationships as well as to provide quality services to their patients. The paper
      concludes by recommending how oncology nursing competencies can be improved.

PMID- 23534717
TI  - Racial and social economic factors impact on the cause specific survival of
      pancreatic cancer: a SEER survey.
AB  - BACKGROUND: This study used Surveillance, Epidemiology and End Results (SEER)
      pancreatic cancer data to identify predictive models and potential socio-economic
      disparities in pancreatic cancer outcome. MATERIALS AND METHODS: For risk
      modeling, Kaplan Meier method was used for cause specific survival analysis. The
      Kolmogorov-Smirnov's test was used to compare survival curves. The Cox
      proportional hazard method was applied for multivariate analysis. The area under
      the ROC curve was computed for predictors of absolute risk of death, optimized to
      improve efficiency. RESULTS: This study included 58,747 patients. The mean follow
      up time (S.D.) was 7.6 (10.6) months. SEER stage and grade were strongly
      predictive univariates. Sex, race, and three socio-economic factors (county level
      family income, rural-urban residence status, and county level education
      attainment) were independent multivariate predictors. Racial and socio-economic
      factors were associated with about 2% difference in absolute cause specific
      survival. CONCLUSIONS: This study s found significant effects of socio-economic
      factors on pancreas cancer outcome. These data may generate hypotheses for trials
      to eliminate these outcome disparities.

PMID- 23534718
TI  - Expression of fragile histidine triad (FHIT) and WW-domain oxidoreductase gene
      (WWOX) in nasopharyngeal carcinoma.
AB  - The aim of the present study was to analyze the expression of FHIT and WWOX in
      nasopharyngeal carcinoma (NPC) and correlations with clinical pathologic
      features. mRNA expression of the FHIT and WWOX was assessed by real-time
      fluorescent relatively quantitative PCR in 61 NPC tissues and 45 non-cancerous
      nasopharyngeal tissues. As a result, mRNA expression levels of both FHIT and WWOX
      were significantly lower in NPC patients than in control samples (P=0.049 and
      0.045, respectively). Moreover, the mRNA expression of both had an inverse
      relation with larger invasive range (P=0.035 and 0.048, respectively), poor
      histologic differentiation (P=0.012 and 0.016) and advanced clinical stage
      (P=0.026 and 0.038). Consistency was found between expression of FHIT and WWOX in
      the same NPC tissues (r=0.681, P=0.00). In conclusion, synergy between FHIT and
      WWOX may exist in the development of NPC so that the two factors may be
      considered as important genetic markers. Detecting the expression of FHIT and
      WWOX should provide clinically significant information relevatn to tumor
      diagnosis, progression and treatment modalities for NPC.

PMID- 23534719
TI  - Tanshinone IIA reverses the malignant phenotype of SGC7901 gastric cancer cells.
AB  - BACKGROUNDS: Tanshinone IIA (TIIA), a phenanthrenequinone derivative extracted
      from Salvia miltiorrhiza BUNGE, has been reported to be a natural anti-cancer
      agent in a variety of tumor cells. However, the effect of TIIA on gastric cancer
      cells remains unknown. In the present study, we investigated the influence of
      TIIA on the malignant phenotype of SGC7901 gastric cancer cells. METHODS: Cells
      cultured in vitro were treated with TIIA (0, 1, 5, 10 MUg/ml) and after
      incubation for different periods, cell proliferation was measured by MTT method
      and cell apoptosis and cell cycling were assessed by flow cytometry (FCM). The
      sensitivity of SGC7901 gastric cancer cells to anticancer chemotherapy was
      investigated with the MTT method, while cell migration and invasion were examined
      by wound-healing and transwell assays, respectively. RESULTS: TIIA (1, 5, 10
      MUg/ml) exerted powerful inhibitory effects on cell proliferation (P < 0.05, and
      P < 0.01), and this effect was time- and dose-dependent. FCM results showed that
      TIIA induced apoptosis of SGC7901 cells, reduced the number of cells in S phase
      and increased those in G0/G1 phase. TIIA also significantly increased the
      sensitivity of SGC7901 gastric cancer cells to ADR and Fu. Moreover, wound
      healing and transwell assays showed that TIIA markedly decreased migratory and
      invasive abilities of SGC7901 cells. CONCLUSIONS: TIIA can reverse the malignant
      phenotype of SGC7901 gastric cancer cells, indicating that it may be a promising
      therapeutic agent.

PMID- 23534720
TI  - Functional PstI/RsaI polymorphisms in the CYP2E1 gene among south Indian
      populations.
AB  - Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing
      enzyme expressed in liver, kidney, nasal mucosa, brain, lung, and other tissues.
      CYP2E1 is inducible by ethanol, acetone, and other low-molecular weight
      substrates and may mediate development of chemically-mediated cancers. CYP2E1
      polymorphisms alter the transcriptional activity of the gene. This study was
      conducted in order to investigate the allele frequency variation in different
      populations of Andhra Pradesh. Two hundred and twelve subjects belonging to six
      populations were studied. Genotype and allele frequency were assessed through
      TaqMan allelic discrimination (rs6413419) and polymerase chain reaction
      sequencing (-1295G>C and -1055C>T) after DNA isolation from peripheral
      leukocytes. The data were compared with other available world populations. The
      SNP rs6413419 is monomorphic in the present study, -1295G>C and -1055C>T are less
      polymorphic and followed Hardy-Weinberg equilibrium in all the populations
      studied. The -1295G>C and -1055C>T frequencies were similar and acted as
      surrogates in all the populations. Analysis of HapMap populations data revealed
      no significant LD between these markers in all the populations. Low frequency of
      CYP2E1 c2 could be useful in the understanding of south Indian population gene
      composition, alcohol metabolism, and alcoholic liver disease development.
      However, screening of additional populations and further association studies are
      necessary. The heterogeneity of Indian population as evidenced by the different
      distribution of CYP2E1 c2 may help in understanding the population genetic and
      evolutionary aspects of this gene.

PMID- 23534721
TI  - A multicenter matched case control study of breast cancer risk factors among
      women in Karachi, Pakistan.
AB  - BACKGROUND: Breast cancer (BC), the most common female cancer in Pakistan, is
      associated with a very high mortality. However, the roles of individual risk
      factors for BC among Pakistani women are still controversial. To assess potential
      risk factors for BC, a matched case-control study was conducted in two tertiary
      care hospitals of Karachi, Pakistan. MATERIALS AND METHODS: The study population
      included 297 pathologically confirmed incident cases of BC patients diagnosed
      between January 2009 and December 2010. 586 controls without any history of BC
      were matched on a hospital basis, within 5 years of patient ages. RESULTS: Family
      history of BC (MOR=1.72; 95%CI: 1.10, 2.80 for first degree vs. none), single
      marital status (MOR=1.55; 95%CI: 1.10, 2.39 for single women vs. married women),
      older age at menopause (MOR=3.92; 95%CI: 2.52, 6.18 for menopausal women aged
      below 45 years, MOR=6.42; 95%CI: 3.47, 11.98 for menopausal women above 45 years
      of age compared with premenopausal women) conferred an increased risk of BC for
      women. Increasing parity decreased the risk of BC (MOR=0.90; 95%CI: 0.85, 0.97
      for each live birth). Intake of Vitamin D supplements (MOR=0.30; 95%CI: 0.12,
      0.81 for <3 years and MOR=0.27; 95%CI: 0.13, 0.56 for >3 years) was protective
      compared to non-users of Vitamin D. CONCLUSIONS: This study confirmed only few of
      the recognized risk factors in Pakistani women. The protective effect of Vitamin
      D is important from public health perspective and needs to be further explored
      through a randomized controlled trial.

PMID- 23534722
TI  - Gene polymorphism of XRCC1 Arg399Gln and cervical carcinoma susceptibility in
      Asians: a meta-analysis based on 1,759 cases and 2,497 controls.
AB  - Many epidemiological studies in Asian populations have investigated associations
      between the Arg399Gln gene polymorphism of X-ray repair cross complementing gene
      1 (XRCC1) and risk of cervical carcinoma, but no conclusions have been available
      because of controversial results. Therefore a meta-analysis was conducted for
      clarification. Relevant studies were identified by searching the Pubmed, Embase,
      the Web of Science, Cochrane Collaboration's database, Chinese National Knowledge
      Infrastructure (CNKI), Wanfang database and China Biological Medicinse (CBM)
      until September, 2012. A total of eight studies were included in the present meta
      analysis, which described 1,759 cervical carcinoma cases and 2,497 controls.
      Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) as effect
      size were calculated by fixed-effect or random-effect models. The overall results
      indicated that the XRCC1-399G/A polymorphism was marginally associated with
      cervical carcinoma in Asians: OR (95%CI): 1.16 (1.07, 1.26) in the G/A vs G/G
      inheritance model, 1.24 (0.87, 1.76)in A/A vs G/G inheritance model, 1.13 (1.01,
      1.27) in the dominant inheritance model and 1.18 (0.94, 1.47) in the recessive
      inheritance model. Subgroup analyses on sample size showed no significant
      correlation in the small- sample size group but the large-sample size group was
      consistent with the outcomes of overall meta-analysis. In the subgroup analysis
      by regions, we only found significant association under the G/A vs G/G
      inheritance model in the Chinese population. For the non-Chinese populations, no
      correlation was detected in any genetic inheritance model. In the Asian
      populations, XRCC1-399G/A gene polymorphism was implied to be associated with
      cervical carcinoma.

PMID- 23534723
TI  - Clinicopathological significance of reduced SPARCL1 expression in human breast
      cancer.
AB  - Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1), an
      extracellular matrix glycoprotein, has been implicated in the pathogenesis of
      several disorders including cancer. However, little is known about the expression
      and significance of SPARCL1 in human breast cancer. The aim of this study was to
      determine the expression pattern and clinicopathological significance of SPARCL1
      in a Chinese breast cancer cohort. mRNA and protein expression of SPARCL1 in
      human breast cancer cell lines and breast cancer tissues was detected using the
      reverse transcription-polymerase chain reaction, real-time quantitative PCR, and
      Western blotting, respectively. Immunostaining of SPARCL1 in 282 Chinese breast
      cancer samples was examined and associations with clinicopathological parameters
      were analyzed. Compared to the positive expression in immortalized human breast
      epithelial cells, SPARCL1 was nearly absent in human breast cancer cell lines.
      Similarly, a significantly reduced expression of SPARCL1 was observed in human
      breast cancer tissues compared to that in normal breast epithelial tissues, for
      both mRNA and protein levels (P < 0.001). Immunohistochemical analysis showed
      that strong cytoplasmic immunostaining of SPARCL1 was observed in almost all
      normal breast samples (43/45) while moderate and strong immunostaining of SPARCL1
      was only detected in 191 of 282 (67.7%) breast cancer cases. Moreover, down
      regulation of SPARCL1 was significantly correlated with lymphatic metastasis (P =
      0.020) and poor grade (P = 0.044). In conclusion, SPARCL1 may be involved in the
      breast tumorigenesis and serve as a promising target for therapy of breast
      cancer.

PMID- 23534724
TI  - Effects of Tiam 1 on invasive capacity of gastric cancer cells in vitro and
      underlying mechanisms.
AB  - OBJECTIVE: To investigate changes in the invasive capacity of gastric cancer
      cells in vitro after expression inhibition of T lymphoma invasion and metastasis
      inducing factor 1 (Tiam 1) and underlying mechanisms. METHODS: Using adhesion
      selection, two subpopulations with high (MH) or low (ML) invasive capacity were
      separated from the human gastric cancer cell line MKN-45 (M0). Tiam 1 antisense
      oligodeoxynucleotide (ASODN) was transfected into MH cells with liposomes, and
      expression of Tiam 1 mRNA and protein was determined by RT-PCR and quantitative
      cellular-ELISA. Changes in the cytoskeleton, invasive capacity in vitro and
      expression of ras-related C3 botulinum toxin substrate 1 (Rac 1), integrin beta1
      and matrix metalloproteinase 2 (MMP 2) between Tiam 1 ASODN transfected MH cells
      and non-transfected cells were observed by HE staining, cytoskeletal protein
      staining, scanning electron microscopy, Boyden chamber tests and cyto
      immunohistochemistry. RESULTS: A positive correlation existed between the
      expression level of Tiam l mRNA or protein and the invasion capacity of gastric
      cancer cells. After ASODN treatment (0.43 MUM for 48 h), Tiam 1 mRNA
      transcription and protein expression in MH cells were decreased by 80% and 24%
      respectively (P < 0.05), compared with untreated controls, while invasive
      capacity in vitro was suppressed by 60% (P < 0.05). Morphologic and
      ultrastructural observation also showed that ASODN-treated MH cells exhibited
      smooth surfaces with obviously reduced filopodia and microspikes, which resembled
      M0 and ML cells. Additionally, cytoskeletal distribution dramatically altered
      from disorder to regularity with reduced long filament-like structure,
      projections, pseudopodia on cell surface, and with decreased acitn-bodies in
      cytoplasm. After Tiam 1 ASODN treatment, the expression of Rac 1 and Integrin
      beta1 in MH cells was not affected (P > 0.05), but that of MMP 2 in MH cells was
      significantly inhibited compared with untreated cells (P < 0.05). CONCLUSION:
      Over-expression of Tiam-1 contributes to the invasive phenotype of gastric cancer
      cells. Inhibition of Tiam 1 expression could impair the invasive capacity of
      gastric cancer cells through modulating reconstruction of the cytoskeleton and
      regulating expression of MMP 2.

PMID- 23534725
TI  - Burdens, needs and satisfaction of terminal cancer patients and their caregivers.
AB  - OBJECTIVES: Terminal cancer patients and their caregivers often experience
      traumatic stress and need many types of assistance. In the present study we
      interviewed terminally ill cancer patients and caregivers to determine how much
      burden they experienced and to find out what factors are most important for
      satisfaction. DESIGN: We constructed a questionnaire including overall care
      burden and needs experienced, and administered it to 659 terminal cancer patients
      and 659 important caregivers at 11 university hospitals and 1 national cancer
      center in Korea. RESULTS: Finally, 481 terminal cancer patients and 381
      caregivers completed the questionnaire. Care burden was not insubstantial in both
      and the caregiver group felt more burden than the patient group (P <0.001). While
      the patient group needed financial support most (39.0%), the caregiver group
      placed greatest emphasis on discussion about further treatment plans (44.8%).
      Stepwise multiple logistic regression analyses showed that in the patient group,
      patient's health status (OR, 2.03; 95% CI, 1.16-3.56) and burden (OR, 2.82; 95%
      CI, 1.76-4.50) influenced satisfaction about overall care, while in the caregiver
      group, high education level'(OR, 1.84; 95% CI, 1.76-4.50), burden (OR, 2.94; 95%
      CI, 1.75-4.93) and good family function (OR, 1.94; 95% CI, 1.24-3.04) were
      important. CONCLUSIONS: Our study showed that burden was great in both terminal
      cancer patients and their caregivers and was perceived to be more severe by
      caregivers. Our study also showed that burden was the factor most predicting
      satisfaction about overall care in both groups.

PMID- 23534726
TI  - Methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous
      cell carcinoma susceptibility: a meta-analysis of case-control studies.
AB  - BACKGROUND: Genetic factors and environmental factors play a role in pathogenesis
      of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the
      association of folate intake and Methylenetetrahydrofolate reductase C677T
      polymorphism with ESCC was conflicting. We conducted a meta-analysis to
      investigate the association of MTHFR C677T and folate intake with esophageal
      cancer risk. METHODS: MEDLINE, EMBASE and the Chinese Biomedical Database were
      searched in our study. The quality of studies were evaluated by predefined scale,
      and The association of polymorphisms of MTHFR C677T and folate intake and ESCC
      risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs).
      RESULTS: 19 studies (4239 cases and 5575 controls) were included for meta
      analysis. A significant association was seen between individuals with MTHFR 677
      CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC
      risk (p<0.05). Low intake of folate had significantly higher risk of esophageal
      cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high
      intake of folate did not find significant high risk of esophageal cancer among
      individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. CONCLUSIONS: Our meta
      analysis indicated the folate intake and MTHFR 677CT/TT are associated with the
      risk of ESCC, and folate showed a significant interaction with polymorphism of
      MTHFR C677T.

PMID- 23534727
TI  - Clinicopathologic characteristics and prognoses for multicentric occurrence and
      intrahepatic metastasis in synchronous multinodular hepatocellular carcinoma
      patients.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers
      worldwide, and the outcomes for patients are still poor. It is important to
      determine the original type of synchronous multinodular HCC for preoperative
      assessment and the choice of treatment therapy as well as for the prediction of
      prognosis after treatment. AIMS: To analyze clinicopathologic characteristics and
      prognoses in patients with multicentric occurrence (MO) and intrahepatic
      metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC).
      METHODS: The study group comprised 42 multinodular HCC patients with a total of
      112 nodules. The control group comprised 20 HCC patients with 16 single nodular
      HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA
      (mtDNA) D-loop region was sequenced, and the patients of the study group were
      categorized as MO or IM based on the sequence variations. Univariate and
      multivariate analyses were used to determine the important clinicopathologic
      characteristics in the two groups. RESULTS: In the study group, 20 cases were
      categorized as MO, and 22 as IM, whereas all 20 cases in the control group were
      characterized as IM. Several factors significantly differed between the IM and MO
      patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor
      nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and
      the histological grade of the primary nodule. Multivariate analysis further
      demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus
      were independent factors differentiating between IM and MO patients. The tumor
      free survival time of the MO subjects was significantly longer than that of the
      IM subjects (25.7 ? 4.8 months vs. 8.9 ? 3.1 months, p=0.017). Similarly, the
      overall survival time of the MO subjects was longer (31.6 ? 5.3 months vs. 15.4 ?
      3.4 months, p=0.024). The multivariate analysis further demonstrated that the
      original type (p=0.035) and Child-Pugh grade (p<0.001) were independent
      predictors of tumor-free survival time. Cirrhosis (p=0.011), original type
      (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall
      survival time. CONCLUSIONS: HBeAg, cumulative tumor size, tumor nodule location,
      cirrhosis, portal vein and/or microvascular tumor embolus and histological grade
      of the primary nodule are important factors for differentiating IM and MO. MO HCC
      patients might have a favorable outcome compared with IM patients.

PMID- 23534728
TI  - Factors associated with discontinuation of complementary and alternative medicine
      among Korean cancer patients.
AB  - OBJECTIVES: The purpose of this study was to determine patient characteristics
      and other factors associated with discontinuation of complementary and
      alternative medicine (CAM) among cancer patients in Korea. METHODS: A national,
      multicenter, cross-sectional survey of cancer patients was performed in which 674
      of 2,661 patients were analyzed for their use of CAM after cancer diagnosis.
      Multiple logistic regression was used to identify the factors related to CAM
      discontinuation. RESULTS: Among the surveyed cancer patients, 25.3% (674 of
      2,661) had used CAM, whereas 38.3% (258 of 674) of those with CAM experience had
      discontinued CAM therapy. The most frequently used form of CAM was herbs (43.5%).
      The major reasons for the discontinuation of CAM included absence of effects
      (23.9%), financial burden (22.9%), and physician opposition (13.7%). Other
      factors associated with the discontinuation of CAM included metastatic cancer (OR
      = 2.06), a long duration of cancer treatment (OR = 3.34), dissatisfaction (OR =
      4.34), and side effects (OR = 4.23) of CAM therapy. CONCLUSIONS: For cancer
      patients to correctly employ CAM therapy, increase their satisfaction, and reduce
      their side effects, efforts should be made to analyze the cost effectiveness of
      CAM, and valid information must be provided to physicians and cancer patients.

PMID- 23534729
TI  - XPD Lys751Gln and Asp312Asn polymorphisms and gastric cancer susceptibility: a
      meta-analysis of case-control studies.
AB  - BACKGROUND: Published data regarding the association between xeroderma
      pigmentosum group D (XPD) Lys751Gln and Asp312Asn polymorphisms and gastric
      cancer susceptibility havew been inconclusive. This meta-analysis was therefore
      performed toobtain a more precise estimation of any relationship. MATERIALS AND
      METHODS: A comprehensive literature search was conducted to identify all case
      control studies of Lys751Gln and Asp312Asn polymorphisms and susceptibility to
      gastric cancer. Summary odds ratios (ORs) and its 95% confidence intervals (95%
      CIs) were calculated using a random-effects model with the software STATA
      (version10.0). RESULTS: A total of 12 case-control studies including 3,147 cases
      and 4,736 controls were included. Overall, no significant associations were found
      in some models (for Lys751Gln: Lys/Gln vs Lys/Lys: OR=1.144, 95% CI=0.851-1.541,
      Gln/Gln vs Lys/Lys: OR=1.215, 95% CI = 0.740-1.955, dominant model: OR=1.137, 95%
      CI=0.818-1.582; recessive model: OR=1.123, 95% CI=0.765-1.650; for Asp312Asn:
      Asp/Asn vs Asp/Asp: OR=1.180, 95% CI=0.646-2.154, dominant model: OR=1.380, 95%
      CI = 0.812-2.346), but significantly elevated susceptibility was found for
      Asp312Asn polymorphism in some models (Asn/Asn vs Asp/Asp: OR=2.045, 95% CI=1.254
      3.335, recessive model: OR=1.805, 95% CI =1.219-2.672 ), for the additive model,
      the XPD Lys751Gln and Asp312Asn polymorphisms were not significantly associated
      with gastric cancer susceptibility. In stratified analyses, significantly
      elevated susceptibility was found for some models in the Chinese population.
      CONCLUSION: This meta-analysis suggested the XPD Asp312Asn polymorphism might be
      a potential biomarker of gastric cancer susceptibility in overall population,
      while both XPD Lys751Gln and Asp312Asn polymorphisms might be risk factors of
      gastric cancer susceptibility in Chinese.

PMID- 23534730
TI  - Induction of mitochondrial-mediated apoptosis by Morinda citrifolia (Noni) in
      human cervical cancer cells.
AB  - Cervical cancer is the second most common cause of cancer in women and has a high
      mortality rate. Cisplatin, an antitumor agent, is generally used for its
      treatment. However, the administration of cisplatin is associated with side
      effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant
      product, has been shown to have anti-cancer properties. In this study, we used
      Noni, cisplatin, and the two in combination to study their cytotoxic and
      apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We
      demonstrate here, that Noni/Cisplatin by themselves and their combination were
      able to induce apoptosis in both these cell lines. Cisplatin showed slightly
      higher cell killing as compared to Noni and their combination showed additive
      effects. The observed apoptosis appeared to be mediated particularly through the
      up-regulation of p53 and pro-apoptotic Bax proteins, as well as down- regulation
      of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentation in the
      activity of caspase-9 and -3 was also observed, suggesting the involvement of the
      intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa
      and SiHa cell lines.

PMID- 23534731
TI  - Association between C-reactive protein and risk of cancer: a meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND: Associations between elevated C-reactive protein (CRP) and cancer
      risk have been reported for many years, but the results from prospective cohort
      studies remains controversial. A meta-analysis of prospective cohort studies was
      therefore conducted to address this issue. METHODS: Eligible studies were
      identified by searching the PubMed and EMBASE up to October 2012. Pooled hazard
      ratios (HR) was calculated by using random effects model. RESULTS: Eleven
      prospective cohort studies involving a total of 194,796 participants and 11,459
      cancer cases were included in this meta-analysis. The pooled HR per natural log
      unit change in CRP was 1.105 (95% confidence interval (CI): 1.033-1.178) for all
      cancer, 1.308 (95% CI: 1.097-1.519) for lung cancer, 1.040 (95% CI: 0.910-1.170)
      for breast cancer, 1.063 (95% CI: 0.965-1.161) for prostate cancer, and 1.055
      (95% CI: 0.925-1.184) for colorectal cancer. Dose-response analysis showed that
      the exponentiated linear trend for a change of one natural log unit in CRP was
      1.012 (95% CI: 1.006-1.018) for all-cancer. No evidence of publication bias was
      observed. CONCLUSIONS: The results of this meta-analysis showed that the elevated
      levels of CRP are associated with an increased risk of all-cancer, lung cancer,
      and possibly breast, prostate and colorectal cancer. The result supports a role
      of chronic inflammation in carcinogenesis. Further research effort should be
      performed to identify whether CRP, as a marker of inflammation, has a direct role
      in carcinogenesis.

PMID- 23534732
TI  - Clinicopathological features of patients with malignant mesothelioma in a
      multicenter, case-control study: no role for ABO-Rh blood groups.
AB  - BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial
      surfaces. Previous studies have observed an association between ABO blood groups
      and risk of certain malignancies, including pancreatic and gastric cancer;
      however, no information on any association with MM risk is available. The aim of
      this study was to investigate possible associations amoong MM clinicopathological
      features and ABO blood groups and Rh factor. MATERIALS AND METHODS: In 252
      patients with MM, the ABO blood group and Rh factor were examined and compared
      with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red
      Crescent between 2004 and 2011. The relationship of blood groups with various
      clinicopathological features were also evaluated in the patient group. RESULTS:
      The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8%
      of patients had a history of exposure to asbestos, 60.7% of patients had a
      smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of
      patients had mixed histology. Overall, the ABO blood group distribution of the
      252 patients with MM was comparable with the general population. The median
      overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months).
      The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively
      (p=0.396). First line chemotherapy was administered to 118 patients. The median
      OS of patients on pemetrexed or gemcitabine was longer than patient who was not
      administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9
      11.0); p<0.001]. CONCLUSIONS: The results of this study suggest that patients
      with MM can benefit from treatment with pemetrexed or gemcitabine in combination
      with cisplatin. We did not observe a statistically significant association
      between ABO blood group and risk of MM.

PMID- 23534733
TI  - Living experiences of male spouses of patients with metastatic cancer in Taiwan.
AB  - BACKGROUND: Cancer is the leading cause of death in Taiwan. Spouses are generally
      the main caregivers of affected patients but previous studies have seldom
      investigated the needs of male spouses of patients with metastatic cancer.
      PURPOSE: To explore the lived experiences of such male spouses. METHODS: A
      qualitative design using in-depth interviews was conducted with male spouses of
      patients with metastatic cancer being treated at the oncology outpatient
      department in a teaching hospital in northern Taiwan. RESULTS: Nine participants
      aged 31-78 were interviewed. Content analysis of the interviews revealed five
      themes: suffering and struggling, difficulty in focusing on communication and
      interaction, shouldering responsibility, cherishing the love between husband and
      wife, and enabling each other to live better. This study demonstrated how male
      spouse experienced physical and psychological suffering when their wives suffered
      from metastatic cancer. They had to bear the pain of their wife's suffering, and
      also had to shoulder the responsibility for everything. All their efforts were
      put towards enabling each other to live a better life. They cherished the rest of
      the time they could spend with their wives, even though they had to live a hard
      life. As the male spouses of patients with metastatic cancer, the participants
      exhibited both the masculinity of men and the ability to express care and
      tenderness. CONCLUSIONS: The results showed that male spouses need more attention
      in terms of communication and bearing with suffering. Health care professionals
      should more actively understand the needs and provide assistance when facing the
      male spouse of patients with cancer, so as make sure that they possess the
      ability to take care of their wives. Health care professionals should also assist
      and properly act as a bridge of communication between husbands and wives.

PMID- 23534734
TI  - Protective effects of Scutellaria barbata against rat liver tumorigenesis.
AB  - Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is used
      to treat cancers, inflammation, and urinary diseases. This study aimed to
      determine any protective effects of S. barbata crude extract (CE-SB) against rat
      liver tumorigenesis induced by diethylnitrosamine (DENA). Liver malfunction
      indices in serum were measured by biochemical examination. Hematoxylin and eosin
      staining was performed to examine liver pathology. Contents of malondialdehyde
      (MDA) and superoxide dismutase (SOD) were measured in liver homogenates to
      evaluate oxidative stress. The levels of liver malfunction indices in the CE-SB
      groups, especially in the CE-SB high dose group, were lower than that of the
      model group (P<0.05). The results from histological examination indicated that
      the number of liver nodules in the CE-SB groups decreased compared with the model
      group (P<0.05). Content of MDA determined in liver was significantly decreased,
      and level of SOD elevated by CE-SB. CE-SB can inhibit experimental liver
      tumorigenesis and relieve hepatic injury in rats.

PMID- 23534735
TI  - Socio-economic factors influencing tumor presentation and treatment options in
      Chinese breast cancer patients.
AB  - The impact of income and education level on the clinical and pathologic
      characteristics, implementation of clinical breast examination (CBE), and
      treatment patterns of a small population of Chinese female breast cancer patients
      was studied in order to provide a theoretical basis and statistical reference for
      further nationwide research. We included 484 pathologically confirmed female
      primary breast cancer inpatients of the First Affiliated Hospital of Medical
      College of Xi'an Jiaotong University from February 2003 to January 2004. All
      cases were reviewed and relevant information was collected using a designed case
      report form (CRF). Chi- square tests, rank-sum tests, and Fisher's exact tests
      were used in the analysis. Our analysis showed that: (1) women in different
      occupation groups had significant differences in tumor size, pre-operative
      mammography, surgical options, post-operative estrogen receptor (ER), progestin
      receptor (PR) and human epidermal growth factor receptor 2 (Her2) status, and
      post-operative radiotherapy and chemotherapy (P < 0.05); and (2) women with
      different education levels had statistically significant differences in tumor
      size, post-operative ER, PR and Her2 status, and post-operative chemotherapy,
      radiotherapy, and endocrine therapy (P < 0.05). In Xi'an, China, women in low
      income occupations or with low education levels are more likely to have advanced
      tumor stages at presentation, lower implementation rate of clinical breast
      examination, and less treatment.

PMID- 23534736
TI  - Salivary gland tumors: a clinicopathologic study of 366 cases in southern Iran.
AB  - BACKGROUND: Salivary gland tumors (SGT) are one of the most complex human
      neoplasms, demonstrating variations in their clinicopathological profile related
      to racial and geographic differences. Few studies with large samples have been
      reported in Iran. We here investigated a large group of patients in southern
      Iran. MATERIALS AND METHODS: In this retrospective study, all cases of primary
      epithelial salivary gland tumors, which had been recorded in a 5 years period
      from 2005-2009, were enrolled. Clinical data such as histopathologic type and
      site of the lesion as well as patients' age and gender were analyzed. RESULTS:
      Data of 366 cases of SGTs were recorded. Pleomorphic adenoma (80.2%) and adenoid
      cystic carcinoma (46.6%) were the most common benign and malignant neoplasms.
      Male to female ratio (M/F) and the mean age of patients were 1:1.05 and 37.7 for
      benign tumors while they were 1.2:1 and 50.6 for malignant tumors, respectively.
      Parotid and minor salivary glands were involved more frequently. CONCLUSIONS:
      Although the salivary gland tumours encountered were similar in most of their
      characteristics to those reported in other countries, some differences such as
      relative frequency and age and gender prevalence were discovered. These findings
      should help surgeons and pathologists for more accurate diagnosis, management and
      treatment.

PMID- 23534737
TI  - Chronic hepatitis B virus infection and risk of pancreatic cancer: a meta
      analysis.
AB  - OBJECTIVES: A number of studies have shown that chronic hepatitis B virus
      infection is implicated in susceptibility to pancreatic cancer. However, the
      results are still controversial. This meta-analysis aimed to quantitatively
      assess the relationship between chronic hepatitis B virus infection and incidence
      of pancreatic cancer of cohort and case-control studies. METHODS: A literature
      search was performed for entries from 1990 to 2012 using PUBMED and EMBASE.
      Studies were included if they reported odds ratios (ORs) and corresponding 95%
      CIs of pancreatic cancer with respect to the infection of hepatitis B virus.
      RESULTS: Eight studies met the inclusion criteria, which included five case
      control studies and three cohort studies. Compared with individuals who have not
      infection of hepatitis B virus, the pooled OR of pancreatic cancer was 1.403
      (95%CI: 1.139-1.729, P=0.001) for patients with hepatitis B virus infection. Sub
      group analysis by study design showed that the summary OR was 1.43 (95%CI: 1.06
      1.94, P=0.021) when pooling case-control studies and 1.31 (95%CI: 1.00- 1.72,
      P=0.05) when pooling cohort studies. CONCLUSION: Findings from this meta-analysis
      suggest that chronic hepatitis B virus infection may increase the risk of
      pancreatic cancer. This relationship needs to be confirmed by further follow-up
      studies.

PMID- 23534738
TI  - Effects of FasL expression in oral squamous cell cancer.
AB  - PURPOSE: To probe the role of FasL in cell apoptosis in oral squamous cell
      carcinomas (OSCCs). METHODS: The expression of Fas/FasL was assessed in 10 cases
      of normal oral epithelium, 38 cases of OSCC and tumor infiltrating lymphocytes
      (TIL), and 11 cases of metastatic lymph nodes by immunohistochemistry. Apoptosis
      of tumor cells and TIL was detected by terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling assay (TUNEL). FasL-induction of T cell
      apoptosis was tested by co-culture assay in vitro with SCC-9 and Jurkat T cells.
      RESULTS: The 10 cases of normal oral epithelium all demonstrated extensive
      expression of Fas, the positive rate being largely down-regulated in OSCC (21/38)
      (P<0.05) compared to the normal (10/10). At the same time, the positive rate of
      FasL significantly increased in OSCC (P<0.05) especially those with lymph node
      metastasis (P<0.05). The positive rates of Fas in well and middle differentiated
      OSCC were higher than those in poor differentiated OSCC (P<0.05). The AI of tumor
      cells in Fas-positive OSCC was remarkably higher than that in Fas-negative OSCC
      (P<0.01), with a positive correlation between Fas expression and cell
      differentiation as well as apoptosis (r=0.68, P<0.01). The AI of tumor cells in
      FasL positive OSCC was remarkably lower than that in control while the AI of TIL
      was higher than in FasL negative OSCC (P< 0.05). The AI of tumor cells reversely
      correlated with that of TIL (r = -0. 72, P<0.05). It was found that SCC-9 cells
      expressing functional FasL could induce apoptosis of Jurkat cells as demonstrated
      by co-culture assays. As a conclusion, it is evident that OSCC cells expressing
      FasL can induce apoptosis in Fas-expressing T cells. CONCLUSIONS: In progression
      of OSCC, expression of the Fas/FasL changes significantly. The results suggest
      that FasL is a mediator of immune privilege in OSCC and may serve as an marker
      for predicting malignant change in oral tissues.

PMID- 23534739
TI  - Low expression of tyrosine-protein phosphatase nonreceptor type 12 is associated
      with lymph node metastasis and poor prognosis in operable triple-negative breast
      cancer.
AB  - BACKGROUND: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12)
      expression may be associated with breast cancer growth, proliferation, and
      metastasis. However, the prognostic value of PTPN12 in breast cancer has not been
      clearly identified. PATIENTS AND METHODS: 51 triple-negative breast cancer (TNBC)
      patients and 83 non-TNBC patients with a histopathology diagnosis from October
      2001 to September 2006 were included in this study. Immunohistochemical staining
      for PTPN12 on tissue microarrays was conducted. RESULTS: High PTPN12 expression
      was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expression was
      associated with lymph node status (p = 0.002) and distant metastatic relapse (p =
      0.002) in TNBC patients. Similarly, low PTPN12 expression in non-TNBC patients
      was significantly correlated with lymph node status (p = 0.002), stage (p =
      0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression
      group was associated with longer DFS and OS compared with low PTPN12 expression
      group only in TNBC cases (p = 0.005, p = 0.015), according to univariate Cox
      regression analysis. CONCLUSION: These findings provide evidence that low
      expression of PTPN12 is associated with worse prognosis and may be used as a
      potential prognostic biomarker in TNBC patients.

PMID- 23534740
TI  - Predictive value of baseline plasma D-dimers for chemotherapy- induced
      thrombocytopenia in patients with stage III colon cancer: a pilot study.
AB  - BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is an important cause of
      morbitity in patients with cancer. AIM: To investigate the effect of the baseline
      plasma D-dimer level, an important marker for thrombotic activity, on
      chemotherapy-induced thrombocytopenia in patients with stage III colon cancer.
      MATERIALS AND METHODS: A total of 43 (28 men) eligible patients were divided into
      two groups according to whether they exhibited chemotherapy-induced
      thrombocytopenia: Group 1 (n=21) and Group 2 (n=22). Comparison was made using
      demographic, histopathologic, and laboratory variables. Additionally, baseline
      plasma D-dimer levels underwent receiver operation characteristics curve
      analysis, and areas under the curve were calculated. Sensitivity, specificity,
      and positive and negative likelihood rates were then determined. RESULTS: The
      incidence of chemotherapy-induced thrombocytopenia had a significant correlation
      with baseline platelet count (r=0.568, P=0.031) and baseline plasma D-dimer
      levels (r=0.617, P=0.036). When the cut-off point for the latter was set as 498
      ng/mL, the area under the curve was 0.89 (95%CI: 0.74-0.93), the sensitivity was
      91.4%, the specificity was 89.7%, the positive likelihood rate was 3.64 and the
      negative likelihood rate was 0.24 for chemotherapy-induced thrombocytopenia
      diagnosis. CONCLUSIONS: The baseline level of plasma D-dimer could help to
      differentiate high- risk patients for chemotherapy-induced thrombocytopenia.

PMID- 23534741
TI  - Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate
      reductase in association with the susceptibility to gastric cancer.
AB  - Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated
      with DNA methylation, an epigenetic feature frequently found in gastric cancer.
      We conducted a case-control study to explore the association of MTHFR C677T
      polymorphisms with gastric cancer risk and its relation with the DNA methylation
      of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined
      by methylation-specific PCR after sodium bisulfate modification of DNA, and
      genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism
      7911HT Sequence Detection System. Folate intake was calculated with the aid of a
      questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was
      significantly associated with 2.08 fold risk of gastric cancer when adjusting for
      potential risk factors. Individuals who had an intake of folate above 310 MUg/day
      showed protective effects against gastric cancer risk. The effect of MTHFR C677T
      polymorphisms on the risk of gastric cancer was modified by folate intake and
      methylation status of MGMT (P for interaction <0.05).

PMID- 23534742
TI  - Gender differences in responses towards anti-smoking messages and policy
      implementation among future doctors in Malaysia.
AB  - BACKGROUND: Medical students' views may provide some direction for future policy
      considerations. AIM: The aim of this study was to assess gender differences in
      future doctors' receptiveness to currently implemented anti-smoking messages and
      the effectiveness of those messages. MATERIALS AND METHODS: We administered a
      questionnaire to all students at a medical university in Malaysia, asking how
      frequently they noted anti- smoking policies, anti-smoking campaigns, and anti
      smoking messages in schools. In addition, the questionnaire investigated most
      effective methods to convey these messages. RESULTS: A total of 522 (59.7%)
      students responded. Students were least likely to approve of total bans on
      cigarettes and increasing the price of cigarettes, and most likely to approve of
      bans on use of cigarettes in public places and sales to individuals less than 16
      years old. Approval of total bans on cigarettes was more common in female
      students than in males OR=0.39 (95%CI: 0.18- 0.86). Furthermore, compared to the
      female students, the male students thought that printed media; OR=2.32 (95%CI:
      1.31-4.10), radio; OR=1.93 (95%CI: 1.15-3.22) and the internet; OR=1.96 (95%CI:
      1.15-3.33) were very effective at delivering anti-smoking messages. CONCLUSIONS:
      Gender differences existed in the future doctors' perception of the effectiveness
      of anti-smoking initiatives. Taking this gender difference into account may
      increase the receipt of anti-smoking messages in adolescents.

PMID- 23534743
TI  - Exosomes from murine-derived GL26 cells promote glioblastoma tumor growth by
      reducing number and function of CD8+T cells.
AB  - AIM: Brain tumors almost universally have fatal outcomes; new therapeutics are
      desperately needed and will only come from improved understandins of glioma
      biology. METHODS: Exosomes are endosomally derived 30~100 nm membranous vesicles
      released from many cell types. Examples from GL26 cells were here purified using
      density gradient ultracentrifugation and monitored for effects on GL26 tumor
      growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to
      detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells
      producing intracellular cytokines were analyzed by FACS. RESULTS: In this study,
      exosomes from murine-derived GL26 cells significantly promoted in vivo tumor
      growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26
      cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells.
      Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell
      depletion assays in vivo and LDH release assays in vitro. The treatment of mice
      with exosomes also led to a reduction in the percentages of CD8+T cells in
      splenocytes as determined by FACS analysis. Key features of CD8+T cell activity
      were inhibited, including release of IFN-gamma and granzyme B. There were no
      effects of exosomes on CD4+T cells and NK cells. CONCLUSION: Based on our data,
      for the first time we demonstrated that exosomes from murine derived GL26 cells
      promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a
      potential therapeutic target.

PMID- 23534744
TI  - Surgical perspective of T1799A BRAF mutation diagnostic value in papillary
      thyroid carcinoma.
AB  - BACKGROUND: Throughout Indonesia, thyroid cancer is one of the ten commonest
      malignancies, with papillary thyroid carcinoma (PTC) in our hospital accounting
      for about 60% of all thyroid nodules. Although fine needle aspiration biopsy
      (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as
      indeterminate and second surgery is common for PTC. The aim of this study was to
      establish the diagnostic value and feasibility of testing the BRAF T1799A
      mutation on FNA specimens for improving PTC diagnosis. MATERIALS AND METHODS:
      This prospective study enrolled 95 patients with thyroid nodules and future
      surgery planned. Results of mutational status were compared with surgical
      pathology diagnosis. RESULTS: Of the 70 cases included in the final analysis,
      62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      for BRAF mutation analysis were 36%, 100%, 100% and 48%, respectively. With other
      data findings, nodules with "onset less than 5 year" and "hard consistency" were
      proven as diagnostic determinants for BRAF mutation with a probability of 62.5%.
      This mutation was also a significant risk factor for extra-capsular extension.
      CONCLUSIONS: Molecular analysis of the BRAF T1799A mutation in FNAB specimens has
      high specificity and positive predictive value for PTC. It could be used in the
      selective patients with clinical characteristics to facilitate PTC diagnosis and
      for guidance regarding extent of thyroidectomy.

PMID- 23534745
TI  - TGF-beta-activated kinase-1: a potential prognostic marker for clear cell renal
      cell carcinoma.
AB  - BACKGROUND: TGF-beta-activated kinase-1 (TAK1) has been found to be over
      expressed in a variety of solid malignancies and related to tumor growth. The aim
      of this study was to evaluate the expression level of TAK1 in clear cell renal
      cell carcinoma (ccRCC) and assess its value as a novel prognostic marker.
      METHODS: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal
      tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs
      and 177 samples of ccRCC immunohistochemically for evaluation of relationships
      with clinical characteristics. RESULTS: RT-PCR showed that TAK1 RNA level was
      significantly higher in ccRCC tissues than in the paired ADTs and
      immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples
      compared with ADTs. TAK1 protein expression in 177 ccRCC samples was
      significantly correlated with T stage, N classification, metastasis, recurrence
      and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a
      better survival outcome. TAK1 expression and N stage were independent prognosis
      factors for the overall survival of ccRCC patients. CONCLUSIONS: Overexpression
      of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve
      as a novel prognostic marker.

PMID- 23534746
TI  - Survival rate of extrahepatic cholangiocarcinoma patients after surgical
      treatment in Thailand.
AB  - BACKGROUND: Intra- and extrahepatic cholangiocarcinoma (CCA) is the most common
      cancer in Thailand, especially in the northeast region. Most extrahepatic CCA
      patients consult a doctor at a late stage. Surgery is still the best treatment.
      OBJECTIVES: The aim of this study was to evaluate survival rates and factors
      affecting survival in extrahepatic CCA patients following surgery at Srinagarind
      Hospital, Khon Kaen University, Thailand. MATERIALS AND METHODS: A retrospective
      cohort study was conducted with 58 patients who were diagnosed and treated by
      surgical resection by the same surgeon at Srinagarind Hospital between 2005 and
      2009. The patients were followed up until death or the end of the study (31
      December, 2011). Survival rates were calculated by the Kaplan-Meier method, and
      the Cox proportional hazard model was used to identify independent prognostic
      factors. RESULTS: The total follow-up time was 1,215 person-months, and the
      mortality rate was 50 per 100 person-years. The cumulative 1-, 3-, and 5-year
      survival rates were 62.1%, 21.7% and 10.8%, respectively. The median survival
      time after resection was 15 months. After adjusting for age, gender, lymph node
      metastasis and histological type, resection margin remained as a statistically
      significant prognostic factor for survival following surgery. A positive
      resection margin was associated with a 2.3-fold higher mortality rate than a
      negative margin. CONCLUSIONS: Resection margins are important prognostic factors
      affecting survival of extrahepatic CCA patients after surgery. A negative
      resection margin can reduce the mortality rate by 56%.

PMID- 23534747
TI  - Significance of HCG to distinguish parathyroid carcinoma from benign disease and
      in adding prognostic information: a hospital based study from Nepal.
AB  - OBJECTIVE: To differentiate between benign and malignant hyperparathyroidism on
      the basis of excretion of HCG and its malignant isoforms in urine. MATERIALS AND
      METHODS: This hospital based study was carried out using data retrieved from the
      register maintained in Manipal Teaching Hospital from 1st January, 2008 and 31st
      August, 2012. The variables collected were urinary HCG and HCG malignant isoform,
      calcium and parathyroid hormone. Preceding the study, approval was obtained from
      the institutional research ethical committee. Analysis was by descriptive
      statistics and testing of hypothesis. A p-value of <0.05 (two-tailed) was used to
      establish statistical significance. RESULTS: Out of the 20 cases, 10 were primary
      hyperparathyroidism and the remainder were parathyroid carcinomas. The urinary
      HCG 6.1?0.6 fmol/mgCr was with in normal range in benign hyperthyroidism but was
      markedly elevated in three cases of malignant hyperparathyroidism (maximum value
      of excretion in urine for HCG was 2323 fmol/mgCr). The excretion of malignant
      isoform of HCG in urine was 0 in benign hyperparathyroidsm and in four cases of
      malignant hyperparathyroidism which fell into the category of persistantly low
      HCG. The maximum excretion of the malignant isoform of HCG in urine was 1.8, in
      the category of very high HCG. Calcium and parathyroid hormone were mildly raised
      in benign parathyroidism, while parathyroid hormone was markedly elevated in
      cases of malignant hyperparathyroidism falling into the category of very high
      HCG. CONCLUSIONS: The excretion of urinary HCG in urine has the ability to
      distinguish between parathyroid adenomas and carcinomas and thus has potential to
      become a marker of disease progression in malignant parathyroid disease.

PMID- 23534748
TI  - Somatic mutations of K-ras and BRAF in Thai colorectal cancer and their
      prognostic value.
AB  - BACKGROUND: The study aimed to determine the incidence of K-ras and BRAF
      mutations in colorectal cancers (CRCs) in Thai patients and evaluate association
      with clinicopathological parameters including treatment outcomes in terms of
      event free survival (EFS). MATERIALS AND METHODS: Two-hundred colorectal cancer
      specimens were collected for studies of K-Ras codon 12, 13 and 61, and BRAF codon
      600 by polymerase chain reaction and direct nucleotide sequencing. RESULTS: The
      overall incidence of K-Ras mutations in our patients was 23%. K-ras mutation
      frequencies in CRC stages (AJCC) I, II, III and IV were 6.7%, 16.1%, 23.3% and
      26.6%, respectively (p-value>0.05). The three most common mutation forms were
      G12D, G12V and G13D. K-Ras mutation status was associated with poorer EFS in
      stage I-III CRCs (p-value 0.03). CONCLUSIONS: The study found a lower mutation
      frequency of K-Ras and BRAF compared to reports involving other ethnic groups.
      However, K-Ras mutations did have a negative prognostic value in early-stage
      CRCs.

PMID- 23534749
TI  - Promoting attendance at cervical cancer screening: understanding the relationship
      with Turkish womens' health beliefs.
AB  - BACKGROUND: The aim of the study was to identify the relationship between 'Health
      Belief Model Scale for Cervical Cancer and the Pap Smear Test' subscale scores
      and demographic/gyneco-obstetric characteristics. MATERIALS AND METHODS: This
      cross-sectional study was conducted with 256 women. Data were obtained using the
      'Demographic and Gyneco-Obstetric Identification Form' and the 'Health Belief
      Model Scale for Cervical Cancer and the Pap Smear Test. RESULTS: The percentage
      of women who had heard about the Pap test was 77.7 whereas only 32.4% had
      actually undergone the test. Some 45.7% of the women stated that they did not
      know the reason for having a Pap test. Women who had obtained a Pap smear test
      had statistically significantly fewer perceived barriers than those who had never
      had (p<0.05). Scores with regard to the subscales including 'Benefits of Pap
      Smear Tests and Health Motivation', 'Perceived Seriousness of Cervical Cancer',
      'Susceptibility to Cervical Cancer' and 'Cervical Cancer Health Motivation' did
      not differ with demographic/gyneco-obstetric characteristics such as womens'
      educational level, whether or not young age at first marriage, whether or not
      having family history of female cancer, and whether or not having had a Pap test
      (p>0.05). CONCLUSIONS: Increasing knowledge about benefits of Pap smear tests,
      increasing motivation to obtain Pap Smear Test and increasing perceived
      seriousness of cervical cancer could promote attendance at cervical cancer
      screening. Different strategies are needed for behavioural change. Implementation
      of educational programmes by nurses in a busy environment could result in a major
      clinical change, based on the findings of this study.

PMID- 23534750
TI  - Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1
      (rs1800566) genes in Thai cervical cancer patients with HPV 16 infection.
AB  - The risk of cervical cancer development in women infected with HPV varies in
      relation to the individual host's genetic makeup. Many studies on polymorphisms
      as genetic factors have been aimed at analyzing associations with cervical
      cancer. In this study, single nucleotide polymorphisms (SNPs) in 3 genes were
      investigated in relation to cervical cancer progression in HPV16 infected women
      with lesions. Two thousand cervical specimens were typed by PCR sequencing
      methods for TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566).
      Ninety two HPV16 positive cases and thirty two normal cases were randomly
      selected. Analysis of TP53 (rs1042522) showed a significantly higher frequency in
      cancer samples (OR=1.22, 95%CI=1.004-1.481, p-value=0.016) while differences in
      frequency were not significant within each group (p-value=0.070). The genotype
      distributions of p16 (rs11515 and rs3088440) and NQO1 (rs1800566) did not show
      any significantly higher frequency in cancer samples (p-value=0.106, 0.675 and
      0.132, respectively) or within each group (p-value=0.347, 0.939 and 0.111,
      respectively). The results indicated that the polymorphism in TP53 (rs1042522)
      might be associated with risk of cervical cancer development in HPV16 infected
      women. Further studies of possible mechanisms of influence on cervical cancer
      development would be useful to manage HPV infected patients.

PMID- 23534751
TI  - Effects of allogeneic blood transfusion in patients with stage II colon cancer.
AB  - The aim of the present study was to determine whether allogeneic red blood cell
      transfusions showed a deleterious effect and what might be preoperative risk
      factors for blood transfusion in patients with TNM stage II colon cancer. Total
      470 patients who fulfilled inclusion criteria were selected for a further 10-year
      follow-up study. We found that there were statistical significance between non
      transfused and transfused group in mortality (P=0.018), local recurrence
      (P=0.000) and distant metastasis (P=0.040). Local recurrence and distant
      metastasis between 1 to 3 units and more than 3 units group did not show any
      significant differences. There was no difference in survival rate between non
      transfused and 1 to 3 units group (log rank =0.031, P=0.860). The difference
      between different blood transfusion volume in transfused patients was found
      (78.77% vs 63.83%, P=0.006). Meanwhile, the significant difference of survival
      rate was existed between non-transfused group and more than 3 units group (84.83%
      vs 63.83%, P=0.002 ). Univariate analysis showed the following 3 variables to be
      associated with an increased risk of allogeneic blood transfusions: preoperative
      CEA level (P<0.05), location of tumor (P<0.01) and diameter of tumor (P<0.01).
      Multivariate analysis revealed that location of tumor and diameter of tumor are
      two independent factors for requirement of perioperative transfusions. Therefore,
      allogeneic transfusion increase the postoperative tumor mortality, local
      recurrence and distant metastasis in patients with stage II colon cancer. The
      postoperative tumor mortality, local recurrence and distant metastasis were not
      associated with the blood transfusion volume. The blood transfusion volume was
      associated with the survival rate. Location of tumor and diameter of tumor were
      the independent preoperative risk factors for blood transfusion.

PMID- 23534752
TI  - Clinical impact and reliability of carbonic anhydrase XII in the differentiation
      of malignant and tuberculous pleural effusions.
AB  - OBJECTIVE: To assess the practical utility of pleural fluid carbonic anhydrase
      XII (CAXII) quantification for differential diagnosis of effusions. MATERIALS AND
      METHODS: Fluid was collected prospectively from fifty patients presenting with
      lymphocytic pleural effusions for investigation and CAXII was quantified by
      ELISA. RESULTS: Pleural fluid CAXII concentrations were significantly higher in
      lung cancer patients (n=30) than in tuberculous controls (n=20). The sensitivity
      and specificity of this biomarker were 60%and 75%, respectively. CAXII
      measurement was not inferior to cytological examination in the diagnosis and
      exclusion of pleural effusions from lung cancer patients (sensitivity 60% vs.
      57%; specificity 75% vs. 100%; positive predictive value 77%; negative predictive
      value 54%). In patients with negative cytology, it offered a sensitivity of 54%.
      CONCLUSIONS: Pleural fluid CAXII is elevated in pleural effusions from lung
      cancer patients. Measurement of CAXII may be used in the future as a valuable
      adjunct to cytology in the diagnostic assessment of patients with pleural
      effusions related to lung cancer, especially when cytological examination is
      inconclusive.

PMID- 23534753
TI  - Implication of polymorphisms in DNA repair genes in prognosis of hepatocellular
      carcinoma.
AB  - XRCC1 genetic polymorphisms could be associated with increased risk of various
      cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer.
      We here conducted a study to explore the role of selective SNPs of the XRCC1 and
      XPD genes in the prognosis of HCC. A total of 231 cases were collected, and
      genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn
      was performed by duplex polymerase-chain-reaction with the confronting-two-pair
      primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated
      with a significant difference in the median survival time compared with patients
      carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln
      genotype had a significantly greater survival time than patients carrying Lys/Lys
      and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying
      XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg
      genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD
      Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in
      XRCC1 and XPD may have functional significance in the prognosis of HCC.

PMID- 23534754
TI  - Tax is involved in up-regulation of HMGB1 expression levels by interaction with
      C/EBP.
AB  - The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like
      molecule that plays an important role in the pathogenesis of tumors. In this
      study, real-time polymerase chain reactions and Western blot assays indicated
      that HMGB1 transcriptional activity and protein level are increased in Tax+-T
      cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter
      plasmids (pHLuc1 to pHLuc6) were transfected into Tax--T cells (TaxN, Jurkat) and
      Tax+-T cells (TaxP). We found that promoter activity in Tax+-T cells to be higher
      than that in Tax--T cells, indicating a significant increase in pHLuc6. Bay11
      7082 (NF-kappaB inhibitor) treatment did not block the enhancing effect.
      Chromatin immunoprecipitation assays revealed that Tax was retained on a HMGB1
      promoter fragment encompassing -1163 to -975. Bioinformatics analysis showed six
      characteristic cis-elements for CdxA, AP-1, AML-1a, USF, v-Myb, and C/EBP in the
      fragment in question. Mutation of cis- elements for C/EBP reduced significant
      HMGB1 promoter activity induced by Tax. These findings indicate that Tax enhances
      the expression of HMGB1 gene at the transcriptional level, possibly by
      interacting with C/EBP.

PMID- 23534756
TI  - Employment status and work-related difficulties among family members of
      terminally ill patients compared with the general population.
AB  - BACKGROUND: Although caregiving to patients with terminal illness is known to be
      a stressful burden to family members, little attention has been focused on work
      related problems. We aimed to investigate employment status and work-related
      difficulties of family caregivers of terminal cancer patients, comparing with the
      general population. METHODS: Using structured questionnaires, we assessed family
      caregivers of 481 cancer patients determined by physicians to be terminally ill,
      from 11 university hospitals and the National Cancer Center in Korea. RESULTS:
      Among 381 family caregivers of terminal cancer patients (response rate, 87.6%),
      169 (43.9%) were not working before cancer diagnosis, but currently 233 (63.7%)
      were not working. Compared with the general population (36.5%), the percentage of
      not working among the family caregivers was higher (OR = 2.39; 95% CI= 1.73
      3.29). A major reason for not working was to provide assistance to the patients
      (71.6%). 40.6% of those who continued working and 32.3% of those who not working
      family members reported extreme fatigue. Caregivers of old age, those who were
      female, those with a lower household income, and those caring for patients with a
      low performance status were not working at a more significant rate. CONCLUSION:
      Family caregivers of terminal cancer patients suffer job loss and severe work
      related difficulties, probably due to caregiving itself and to fatigue. We need
      to develop supportive programs to overcome the burden of caregivers of the
      terminally ill.

PMID- 23534755
TI  - Proteomics analysis of gastric epithelial AGS cells infected with Epstein-Barr
      virus.
AB  - Effects of the Epstein-Barr virus (EBV) on cellular protein expression are
      essential for viral pathogenesis. To characterize the cellular response to EBV
      infection, differential proteomes of gastric epithelial AGS cells were analyzed
      with two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser
      desorption/ionization- time of flight (MALDI-TOF) and liquid chromatography
      electrospray/ionization ion trap (LC-ESI-IT) mass spectrometry identification.
      Mass spectrometry identified 9 altered cellular proteins, including 5 up
      regulated and 4 down-regulated proteins after EBV infection. Notably 2-DE
      analysis revealed that EBV infection induced increased expression of heat shock
      cognate 71 kDa protein, actin cytoplasmic 1, pyridoxine-5'-phosphate oxidase,
      caspase 9, and t-complex protein 1 subunit alpha. In addition, EBV infection
      considerably suppressed those cellular proteins of zinc finger protein 2, cyclin
      dependent kinase 2, macrophage-capping protein, and growth/ differentiation
      factor 11. Furthermore, the differential expressional levels of partial proteins
      (cyclin-dependent kinase 2 and caspase 9) were confirmed by Western blot
      analysis.Thus, this work effectively provided useful protein-related information
      to facilitate further investigation of the mechanisms underlying EBV infection
      and pathogenesis.

PMID- 23534757
TI  - Impact of adjuvant chemotherapy cycles on prognosis of resectable stomach cancer:
      a retrospective analysis.
AB  - AIMS: The aim of this study was to investigate the effects of adjuvant
      chemotherapy cycles on the prognosis of patients with post-operative stomach
      cancer through retrospective analysis. METHODS: A total of 128 patients with
      gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy
      consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5
      fluorouracil, according to a defined schedule, were divided into three groups
      according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6
      cycles); and Group III (>6 cycles). RESULTS: The 5-year overall survival (OS) was
      20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow
      up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40%
      in Group II, and 40% in Group III. The OS and RFS in Groups II and III were
      significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and
      P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between
      Groups II and III. Multivariate Cox hazard analysis determined that the number of
      adjuvant chemotherapy cycles was an independent factor that influenced OS and
      RFS. CONCLUSION: Six cycles of adjuvant chemotherapy gave encouraging outcomes in
      patients with resectable gastric cancer. Further prospective randomized
      controlled investigations are warranted in a multi-center setting.

PMID- 23534758
TI  - Let-7c inhibits NSCLC cell proliferation by targeting HOXA1.
AB  - OBJECTIVE: The aim of the present study was to explore mechanisms by which let-7c
      suppresses NSCLC cell proliferation. METHODS: The expression level of let-7c was
      quantified by qRT-PCR. A549 and H1299 cells were transfected with let-7c mimics
      to restore the expression of let-7c. The effects of let-7c were then assessed by
      cell proliferation, colony formation and cell cycle assay. Mouse experiments were
      used to confirm the effect of let-7c on tumorigenicity in vivo. Luciferase
      reporter assays and Western blotting were performed to identify target genes for
      let-7c. RESULTS: HOXA1 was identified as a novel target of let-7c. MTS, colony
      formation and flow cytometry assays demonstrated that forced expression of let-7c
      inhibited NSCLC cell proliferation by inducing G1 arrest in vitro, consistent
      with inhibitory effects induced by knockdown of HOXA1. Mouse experiments
      demonstrated that let-7c expression suppressed tumorigenesis. Furthermore, we
      found that let-7c could regulate the expression of HOXA1 downstream effectors
      CCND1, CDC25A and CDK2. CONCLUSIONS: Collectively, these results demonstrate let
      7c inhibits NSCLC cell proliferation and tumorigenesis by partial direct
      targeting of the HOXA1 pathway, which suggests that restoration of let-7c
      expression may thus offer a potential therapeutic intervention strategy for
      NSCLC.

PMID- 23534759
TI  - Survival analysis of breast cancer patients in northwest Iran.
AB  - BACKGROUND: Breast cancer is the most frequently occurring cancer among Iranian
      women; however limited studies have been conducted to address survival rates.
      OBJECTIVE: The objective was to examine survival rates in Tabriz (Northwest of
      Iran) and compare with those of data reported from other cities and countries.
      METHODS: Survival rates were calculated for one, three, five, seven and ten years
      for 271 breast cancer patients referred to one university clinic during 1997
      2008. RESULTS: Survival analysis demonstrated a lower survival rate compared to
      western countries. CONCLUSIONS: Survival rates for our patients are
      similar/better than other cities in Iran, but lower than certain European
      countries and the US. Further studies with a higher number of patients are now
      required.

PMID- 23534760
TI  - Genetic polymorphisms of glutathione S-transferase M1 and prostate cancer risk in
      Asians: a meta-analysis of 18 studies.
AB  - BACKGROUND: Many studies have investigated associations between the glutathione S
      transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the
      impact of GSTM1 in people who live in Asian countries is still unclear owing to
      inconsistencies across results. METHODS: We searched the PubMed, Web of Science,
      Scopus, Ovid and CNKI databases for studies of associations between the GSTM1
      null genotype and risk of prostate cancer in people who live in Asian countries,
      and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs).
      RESULTS: A total of 18 case-control studies with 2,172 cases and 3,258 controls
      were included in this meta-analysis, which showed the GSTM1 null genotype to be
      significantly associated with increased risk of prostate cancer in people who
      live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001).
      Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004)
      and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of
      publication bias was observed. CONCLUSIONS: This meta- analysis of available data
      suggested that the GSTM1 null genotype does contribute to increased risk of
      prostate cancer in people who live in Asian countries.

PMID- 23534761
TI  - The miR-146a rs2910164 G > C polymorphism and susceptibility to digestive cancer
      in Chinese.
AB  - BACKGROUND: Several studies have reported the role of the miR-146a rs2910164 G >
      C polymorphism as a susceptibility factor for several digestive cancers. However,
      the results have been controversial. Therefore, we conducted the present meta
      analysis to obtain the most reliable estimate of the association. METHODS:
      PubMed, Embase and Web of Science databases were searched. Crude odds ratios
      (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the
      strength of the association between miR-146a rs2910164 G > C polymorphism and
      digestive cancer risk. A total of four eligible studies including 3,447 cases and
      5,041 controls based on the search criteria were included. RESULTS: We observed
      that miR-146a rs2910164 G > C polymorphism was not significantly correlated with
      digestive cancer risks when all studies were pooled into the meta-analysis. While
      we found that miR-146a rs2910164 polymorphism was not associated with gastric
      cancer, it was significantly linked with hepatocellular cancer risk (the
      homozygote codominant model: OR = 1.40, 95% CI = 1.04-1.87). In the stratified
      analysis by ethnicity, significant associations were observed in Chinese
      population for the allele contrast model (OR = 1.25; 95% CI = 1.12-1.38), for the
      homozygote codominant model (OR = 1.62; 95% CI = 1.28-2.04), and for the
      recessive model (OR = 1.38; 95% CI = 1.16-1.64). However, studies with Asian
      groups presented no significant association for all genetic models. CONCLUSIONS:
      This meta-analysis suggests that the miR-146a rs2910164 G > C polymorphism is a
      low-penetrant risk factor for digestive cancers in Chinese.

PMID- 23534762
TI  - Knockdown of Bcl-3 inhibits cell growth and induces DNA damage in HTLV-1-infected
      cells.
AB  - Oncoprotein Bcl-3 is perceived as an unusual member of IkappaB family since it
      can both stimulate and suppress NF-kappaB activation. Aberrant Bcl-3 results in
      increased cell proliferation and survival, suggesting a contribution to malignant
      potential and elevated levels of Bcl-3 have been observed in many HTLV-1-infected
      T cell lines and ATL cells. To investigate the specific roles of Bcl-3 in HTLV-1
      infected cells, we knocked down Bcl-3 expression using shRNA and then examined
      the consequences with regard to DNA damage and cell proliferation, as well as NF
      kappaB activation. The HTLV-1 encoded protein Tax promotes Bcl-3 expression and
      nuclear translocation. In HTLV-1-infected cells, Bcl-3 knockdown obviously
      induced DNA damage. Cell growth and NF-kappaB activation were reduced in HTLV-1
      infected or Tax positive cells when Bcl-3 expression was decreased. Together, our
      results revealed positive roles of Bcl-3 in DNA stabilization, growth and NF
      kappaB activation in HTLV-1-infected cells.

PMID- 23534763
TI  - In vivo evaluation of curcumin-loaded nanoparticles in a A549 xenograft mice
      model.
AB  - Curcumin (Cum) has been reported to have potential chemo-preventive and
      chemotherapeutic activity through influencing various processes, inducing cell
      cycle arrest, differentiation and apoptosis in a series of cancers. However, the
      poor solubility of Cum limits its further applications in the treatment of
      cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared
      with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block
      copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs
      over free Cum in the treatment of lung cancer. In vivo evaluation further
      demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth
      compared to free Cum in an established A549 transplanted mice model. Moreover,
      Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and
      kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to
      inhibit the growth of human lung cancer with little toxicity to normal tissues,
      and could provide a clinically useful therapeutic regimen. They thus merit more
      research to evaluate the feasibility of clinical application.

PMID- 23534764
TI  - Phase II trial of Loubo(r) (Lobaplatin) and pemetrexed for patients with
      metastatic breast cancer not responding to anthracycline or taxanes.
AB  - PURPOSE: This phase II study was undertaken to determine the efficacy and safety
      of Loubo(r) (Lobaplatin) in combination with pemetrexed in treating patients with
      metastatic breast cancer who failed to respond to anthracycline or taxanes.
      PATIENTS AND METHODS: Metastatic breast cancer cases who had previously received
      an anthracycline and a taxane in either adjuvant or metastatic settings, were
      enrolled. All patients were recruited from Jiangsu Cancer Hospital and Research
      Institute, and were treated with Loubo(r) (Lobaplatin) 35 mg/m2 (intravenous; on
      day 1) and pemetrexed 500 mg/m2 (intravenous; on day 1) every 21 days. Efficacy
      and side effects were evaluated after at least two cycles of chemotherapy.
      RESULTS: All eligible 19 patients completed at least 2 cycles of chemotherapy
      with pemetrexed and lobaplatin, and were evaluable. Overall, 3 (15.8%) patients
      achieved partial response, 11 (57.9%) stable disease, 5 (26.3%) progression of
      disease, with no complete remission. Response rate was 15.8%, disease control
      rate was 42.1%. The median survival time was 10.3 months. Neutrophil suppression
      occurred in 36.8% of patients who had grade 2 toxicity, and 26.3% had grade 3,
      26.4% had grade 4. Thrombocytopenia was encountered as follows: 21.1% grade 2,
      15.8% grade 3 and 5.5% grade 4. Incidences of anemia were 10.5% in grade 2, 5.3%
      grade 3 and 0% grade 4. Only 5.3% of patients required packed red blood cell
      transfusion. Grade 3 digestive tract toxicity occurred in 5.5% of patients. Other
      toxicities included elevated transaminase, oral mucositis and skin rashes.
      CONCLUSIONS: The regimen of lobaplatin and pemetrexed is modestly active in
      metastatic breast cancer patients who failed anthracycline or taxanes, and the
      toxicity profile suggesting that the doses of chemotherapy should be further
      modified.

PMID- 23534765
TI  - Prognostic impact of cyclin D1, cyclin E and P53 on gastroenteropancreatic
      neuroendocrine tumours.
AB  - Conventional classifications of gastroenteropancreatic neuroendocrine tumours
      (GEP- NETs) are rather unsatisfactory because of the variation in survival within
      each subgroup. Molecular markers are being found able to predict patient outcome
      in more and more tumours. The aim of this study was to characterize the
      expression of the proteins cyclin D1, cyclin E and P53 in GEP- NETs and assess
      any prognostic impact. Tumor specimens from 68 patients with a complete follow-up
      were studied immunohistochemically for cyclin D1, cyclin E and P53 expression.
      High cyclin D1 and cyclin E immunostaining (>= 5% positive nuclei) was found in
      48 (71%) and 24 (35%) cases, and high P53 staining (>= 10% positive nuclei) in 33
      (49%) . High expression of P53 was more common in gastric neuroendocrine tumors
      and related to malignant behavior, being associate with a worse prognosis on
      univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was
      significantly associated with shorter survival in the univariate analysis
      (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We
      found no significant correlation between the expression of cyclin D1 and any
      clinicopathological variables. Our study indicated a prognostic relevance for
      cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic
      factor from the 2010 WHO Classification which should be evaluated in further
      studies.

PMID- 23534766
TI  - Low-dose docetaxel/cisplatin - leucovorin and 46 hour infusional fluorouracil in
      metastatic gastric carcinoma.
AB  - BACKGROUND: Phase II and III trials of docetaxel, cisplatin and fluorouracil
      (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but
      with high rates of hematologic toxicity in metastatic gastric cancer cases. To
      reduce toxicity while maintaining the efficacy of DCF, we investigated low dose
      docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen).
      PATIENT AND METHODS: Chemotherapy-naive patients with metastatic gastric cancer
      (MGC) received D 60 mg/m2 on day 1 and cisplatin 30 mg/m2 on day 1-2 and the De
      Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/m2/46 h
      continuous infusion) every 3 weeks. The primary endpoint was response rate.
      RESULTS: One hundred twenty patients with a median age of 52.5 years (range, 32
      78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable
      patients, 4 showed complete remission and 36 achieved a partial response. The
      overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable
      disease and 52 (43.3%) progression. The median time to progression was 7 months
      (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The
      most frequent hematological toxicity was leucopenia, which occurred at grade 3/4
      intensity in 24 patients (20%). CONCLUSIONS: Low-dose DC- De Gramont regimen is
      active in MGC with a tolerable toxicity profile.

PMID- 23534767
TI  - Clinical study of tumor angiogenesis and perfusion imaging using multi-slice
      spiral computed tomography for breast cancer.
AB  - OBJECTIVES: To explore the correlation between multi-slice spiral CT (MSCT)
      perfusion parameters and the expression of vascular endothelial growth factor
      (VEGF) as well as matrix metalloproteinase-2 (MMP- 2) in breast cancer. METHODS:
      Forty five breast cancer patients and 16 patients with benign breast tumor, both
      confirmed by pathology examination, were enrolled. All underwent MSCT perfusion
      imaging to obtain perfusion maps and data for parameters including blood flow
      (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not
      receive treatment prior to surgery. The expression of VEGF and MMP-2 were
      examined with both immunohistochemistry and Western blotting. RESULTS: The levels
      of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast
      cancer group (P < 0.01) than the benign tumor group. Relative OD values from
      Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean
      MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast
      cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r
      = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were
      also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). CONCLUSION:
      There is a correlation between breast cancer MSCT perfusion parameters and VEGF
      andMMP-2 expression, which might be useful for detection of breast lesions,
      qualitative diagnosis of breast cancer, and evaluation of breast cancer
      treatment.

PMID- 23534768
TI  - Lower incidence but more aggressive behavior of right sided breast cancer in
      Pakistani women: does right deserve more respect?
AB  - BACKGROUND: The aim of this epidemiological study was to establish the laterality
      of breast cancer (BC) and its association with size, receptor status of the
      primary tumor and bone metastasis (BM) in a local population. MATERIALS AND
      METHODS: This retrospective study included cases of BC from Jan-2009 to Dec-2011
      who were referred for metastatic work up or follow up survey with Technetium-99m
      MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of
      Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521
      were included and all reviewed for age, primary tumor size (PTS), laterality,
      receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2
      Neu receptor, presence or absence of BM with sites of involvement and time
      interval between diagnosis of BC and appearance of BM. RESULTS: The left to right
      sided BC proportion was significantly higher than unity (59%:41%; p<0.001). The
      right sided BC was observed in younger age group (46:52 years; p<0.0001) and with
      a smaller PTS than the left sided (3.43:4.15 cm; p<0.0001). The patients with BM
      had relatively higher negative receptor status with a significant predominance of
      right sided BC. The overall incidence of BM on BS was 28% and relatively higher
      in right than left breast (33%:24% p=0.068). The average number of BM sites was
      also significantly greater for the right side (6:4, P<0.0001). The % cumulative
      risk of BM in right breast was noted at significantly smaller PTS than left side
      with log rank value of 5.579; p<0.05. The Kaplan Meier survival plot for event
      free survival of BM in left sided BC was significantly higher than for the right
      side (log rank value=4.155, p<0.05), with an earlier appearance of BM in right
      BC. CONCLUSIONS: 1) A left sided predominance of BC was seen in local population;
      2) right sided BC had a more aggressive behavior with extensive and earlier
      appearance of BM at relatively younger age, smaller PTS and receptor (s)
      negativity.

PMID- 23534769
TI  - Quality of life in Malay and Chinese women newly diagnosed with breast cancer in
      Kelantan, Malaysia.
AB  - BACKGROUND: Breast cancer is the leading cause of cancer-related death among
      women in Malaysia. A diagnosis is very stressful for women, affecting all aspects
      of their being and quality of life. As such, there is little information on
      quality of life of women with breast cancer across the different ethnic groups in
      Malaysia. The purpose of this study was to examine the quality of life in Malay
      and Chinese women newly diagnosed with breast cancer in Kelantan. MATERIALS AND
      METHODS: A descriptive study involved 58 Malays and 15 Chinese women newly
      diagnosed with breast cancer prior to treatment. Quality of life was measured
      using the Malay version of the European Organization for Research and Treatment
      of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its breast-specific
      module (QLQ-BR23). Socio-demographic and clinical data were also collected. All
      the data were analyzed using SPSS version 20.0. RESULTS: Most of the women were
      married with at least a secondary education and were in late stages of breast
      cancer. The Malay women had lower incomes (p=0.046) and more children (p=0.001)
      when compared to the Chinese women. Generally, both the Malay and Chinese women
      had good functioning quality-of-life scores [mean score range: 60.3-84.8
      (Malays); 65.0-91.1 (Chinese)] and global quality of life [mean score 60.3, SD
      22.2 (Malays); mean score 65.0, SD 26.6 (Chinese)]. The Malay women experienced
      more symptoms such as nausea and vomiting (p=0.002), dyspnoea (p=0.004),
      constipation (p<0.001) and breast-specific symptoms (p=0.041) when compared to
      the Chinese. CONCLUSIONS: Quality of life was satisfactory in both Malays and
      Chinese women newly diagnosed with breast cancer in Kelantan. However, Malay
      women had a lower quality of life due to high general as well as breast-specific
      symptoms. This study finding underlined the importance of measuring quality of
      life in the newly diagnosed breast cancer patient, as it will provide a broader
      picture on how a cancer diagnosis impacts multi-ethnic patients. Once health care
      professionals understand this, they might then be able to determine how to best
      support and improve the quality of life of these women during the difficult times
      of their disease and on-going cancer treatments.

PMID- 23534770
TI  - Diabetes mellitus reduces prostate cancer risk - no function of age at diagnosis
      or duration of disease.
AB  - BACKGROUND: Prior studies examining the relation between diabetes mellitus (DM)
      and prostate cancer risk have reported controversial findings. We examined this
      association by conducting a detailed meta-analysis of the peer-reviewed
      literature. METHODS: A comprehensive search for articles of MEDLINE and EMBASE
      databases and bibliographies of retrieved articles published up to November, 2012
      was performed. Methodological quality assessment of the trials was based on the
      Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0.
      Dose-response regression was conducted with SPSS 19.0. RESULTS: We included 29
      studies in the meta-analysis (13 case-control studies, 16 cohort studies), and
      found an inverse association between DM and prostate cancer (relative risk (RR)
      0.84, 95% confidence interval (CI), 0.78-0.91). An inverse association was also
      observed in non-Asian populations (RR 0.81, 95% CI 0.76-0.87) and population
      based studies (RR 0.80, 95% CI 0.77-0.91). No statistical significance was found
      of the association between prostate cancer risk and the duration of DM (p=0.338),
      and risk seemed not related with the age of DM diagnosis. CONCLUSIONS: This study
      suggested an inverse relationship between DM and prostate cancer, but without
      links to duration of disease or age of diagnosis.

PMID- 23534771
TI  - Polymorphisms in DNA repair genes and risk of glioma and meningioma.
AB  - Polymorphisms in DNA repair genes have been shown to influence DNA repair
      processes and to modify cancer susceptibility. Here we conducted a case-control
      study to assess the role of potential SNPs of DNA repair genes on the risk of
      glioma and meningioma. We included 297 cases and 458 cancer-free controls.
      Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met,
      XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were
      performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1
      Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in
      control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2
      Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different
      between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and
      XRCC3 241T/T were associated with a higher risk when compared with the wild-type
      genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with
      elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg,
      XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of
      gliomas and meningiomas. This finding could be useful in identifying the
      susceptibility genes for these cancers.

PMID- 23534772
TI  - Lack of any association between blood groups and lung cancer, independent of
      histology.
AB  - INTRODUCTION: Lung cancer, the leading cause of cancer deaths, is divided into 2
      main classes based on its biology, therapy and prognosis: non-small cell lung
      cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced
      stage at diagnosis, which is a major obstacle to improving outcomes. It is
      important to define the high risk group patients for early diagnosis and chance
      of cure. Blood group antigens are chemical components on erythrocyte membranes
      but they are also expressed on a variety of epithelial cells. Links between ABO
      blood groups with benign or malignant diseases, such as gastric and pancreas
      cancers, have been observed for a long time. In this study, we aimed to
      investigate any possible relationship between lung cancer histological subtypes
      and ABO-Rh blood groups. MATERIALS AND METHODS: The files of 307 pathologically
      confirmed lung cancer patients were were reviewed retrospectively. Cases with a
      serologically determined blood group and Rh factor were included and those with a
      history of another primary cancer were excluded, leaving a total of 221. The
      distribution of blood groups of the lung cancer patients were compared with the
      distribution of blood groups of healthy donors admitted to the Turkish Red
      Crescent Blood Service in our city in the year 2012. RESULTS: There was no
      significant difference between patients with lung cancer of either type and the
      control group in terms of distribution of ABO blood groups and Rh factor (p:
      0.073). There was also no relationship with non small cell cancer histological
      subtypes. CONCLUSIONS: In this study, we found no relationship between the ABO
      Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first
      analysis of ABO blood groups in SCLC patients.

PMID- 23534773
TI  - Meta-analysis of gene expression data identifies causal genes for prostate
      cancer.
AB  - Prostate cancer is a leading cause of death in male populations across the globe.
      With the advent of gene expression arrays, many microarray studies have been
      conducted in prostate cancer, but the results have varied across different
      studies. To better understand the genetic and biologic mechanisms of prostate
      cancer, we conducted a meta-analysis of two studies on prostate cancer. Eight key
      genes were identified to be differentially expressed with progression. After gene
      co-expression analysis based on data from the GEO database, we obtained a co-
      expressed gene list which included 725 genes. Gene Ontology analysis revealed
      that these genes are involved in actin filament-based processes, locomotion and
      cell morphogenesis. Further analysis of the gene list should provide important
      clues for developing new prognostic markers and therapeutic targets.

PMID- 23534774
TI  - Reliability and validity of the Malay Version of the Breast- Impact of Treatment
      Scale (MVBITS) in breast cancer women undergoing chemotherapy.
AB  - BACKGROUND: Body image dissatisfaction among breast cancer survivors has been
      associated with psychological stress resultant from breast cancer and resultant
      surgery. This study aimed to examine the psychometric properties of the Malay
      Version of the Breast-Impact of Treatment Scale (MVBITS) and to investigate the
      associations of retained factors with the Hospital Anxiety and Depression Scale
      (HADS) and the Rosenberg Self-Esteem Scale (RSES). MATERIALS AND METHODS: The
      MVBITS was 'forward-backward' translated from English to Malay and then
      administered to 70 female breast cancer patients who came to the Oncology Clinic
      of University Malaya Medical Centre, Kuala Lumpur, Malaysia to undergo
      chemotherapy. Principal component analysis (PCA) with varimax rotation was
      performed to explore the factor structure of the MVBITS. Associations of retained
      factors were estimated with reference to Spearman correlation coefficients.
      RESULTS: The internal consistency reliability of MVBITS was good (Cronbach's
      alpha 0.945) and showed temporal stability over a 3-week period. Principal
      component analysis suggested two factors termed as 'Intrusion' and 'Avoidance'
      domains. These factors explained 70.3% of the variance. Factor 1 comprised the
      effects of breast cancer treatment on the emotion and thought, while Factor 2
      informed attempts to limit exposure of the body to self or others. The Factor 1
      of MVBITS was positively correlated with total, depression and anxiety sub-scores
      of HADS. Factor 2 was positively correlated with total and anxiety sub-scores of
      HADS. MVBITS was also positively correlated with the RSES scores. CONCLUSIONS:
      The results showed that the Malay Version of Breast-Impact of Treatment Scale
      possesses satisfactory psychometric properties suggesting that this instrument is
      appropriate for assessment of body change stress among female breast cancer
      patients in Malaysia.

PMID- 23534775
TI  - Can granisetron injection used as primary prophylaxis improve the control of
      nausea and vomiting with low- emetogenic chemotherapy?
AB  - BACKGROUND: The purpose of this study is to examine the risk of uncontrolled
      chemotherapy-induced nausea and vomiting (CINV) among patients receiving low
      emetogenic chemotherapy (LEC) with and without granisetron injection as the
      primary prophylaxis in addition to dexamethasone and metochlopramide. MATERIALS
      AND METHODS: This was a single-centre, prospective cohort study. A total of 96
      patients receiving LEC (52 with and 42 without granisetron) were randomly
      selected from the full patient list generated using the e-Hospital Information
      System (e-His). The rates of complete control (no CINV from days 1 to 5) and
      complete response (no nausea or vomiting in both acute and delayed phases) were
      identified through patient diaries which were adapted from the MASCC Antiemesis
      Tool (MAT). Selected covariates including gender, age, active alcohol
      consumption, morning sickness and previous chemotherapy history were controlled
      using the multiple logistic regression analyses. RESULTS: Both groups showed
      significant difference with LEC regimens (p<0.001). No differences were found in
      age, gender, ethnic group and other baseline characteristics. The granisetron
      group indicated a higher complete response rate in acute emesis (adjusted OR:
      0.1; 95%CI 0.02-0.85; p=0.034) than did the non-granisetron group. Both groups
      showed similar complete control and complete response rates for acute nausea,
      delayed nausea and delayed emesis. CONCLUSIONS: Granisetron injection used as the
      primary prophylaxis in LEC demonstrated limited roles in CINV control.
      Optimization of the guideline-recommended antiemetic regimens may serve as a less
      costly alternative to protect patients from uncontrolled acute emesis.

PMID- 23534776
TI  - Association between physical activity and postoperative complications after
      esophagectomy for cancer: a prospective observational study.
AB  - BACKGROUND: Postoperative complications after esophagectomy can lead to
      considerable patient discomfort and prolonged length of hospital stay. Lack of
      physical activity can be one of the independent risk factors for postoperative
      complications because physical activity is closely related to physical function.
      The objective of this study was to determine whether physical activity among
      esophageal cancer patients decreases their risk of postoperative complications
      after esophagectomy. MATERIALS AND METHODS: We investigated 51 consecutive
      patients with newly diagnosed resectable esophageal cancer who were scheduled to
      receive esophagectomy between January 2009 and November 2011. Demographic,
      clinicopathologic, and treatment information were recorded and physical function
      was measured. The last 7-days short version of the International Physical
      Activity Questionnaire was used to assess physical activity before the operation.
      Stepwise multiple logistic regression analysis was used to determine whether
      preoperative physical activity is related to the risk of postoperative
      complications. RESULTS: Male gender [OR 18.6, (95%CIs: 1.2-284.4); P=0.035], 3
      field lymph node dissection (OR 9.6, [95%CIs: 1.4-66.6]; P=0.022), low-level
      physical activity (OR 28.3, [95%CIs: 3.5-227.7]; P=0.002), and preoperative
      comorbidities [OR 5.9, (95%CIs: 1.1-31.5); P=0.037] were found to be
      independently associated with postoperative complications. CONCLUSIONS: The
      present study shows that low-level physical activity, preoperative comorbidities,
      and 3-field lymph node dissection are independent and significant risk factors
      for postoperative complications after esophagectomy. Although further study is
      required, maintaining high-level physical activity preoperatively may decrease
      the risk of postoperative complications.

PMID- 23534777
TI  - Smoking habits of relatives of patients with cancer: cancer diagnosis in the
      family is an important teachable moment for smoking cessation.
AB  - BACKGROUND: In this study we aimed to determine the rate and habitual patterns of
      smoking, intentions of cessation, dependence levels and sociodemographic
      characteristics of relatives of patients with a diagnosis of cancer. MATERIALS
      AND METHODS: This study was designed by the Turkish Oncology Group, Epidemiology
      and Prevention Subgroup. The relatives of cancer patients were asked to fill a
      questionnaire and Fagerstrom test of nicotine dependence. RESULTS: The median
      ages of those with lower and higher Fagerstrom scores were 40 years and 42 years,
      respectively. We found no evidence of variation between the two groups for the
      remaining sociodemographic variables, including the subject's medical status,
      gender, living in the same house with the patient, their educational status,
      their family income, closeness to their cancer patients or spending time with
      them or getting any help or wanting to get some help. Only 2% of the subjects
      started smoking after cancer was diagnosed in their loved ones and almost 20% of
      subjects had quit smoking during the previous year. CONCLUSIONS: The Fagerstrom
      score is helpful in determining who would be the most likely to benefit from a
      cigarette smoking cessation program. Identification of these people with proper
      screening methods might help us to pinpoint who would benefit most from these
      programs.

PMID- 23534778
TI  - Impact of healthy eating practices and physical activity on quality of life among
      breast cancer survivors.
AB  - Following breast cancer diagnosis, women often attempt to modify their lifestyles
      to improve their health and prevent recurrence. These behavioral changes
      typically involve diet and physical activity modification. The aim of this study
      was to determine association between healthy eating habits and physical activity
      with quality of life among Iranian breast cancer survivors. A total of 100
      Iranian women, aged between 32 to 61 years were recruited to participate in this
      cross-sectional study. Eating practices were evaluated by a validated
      questionnaire modified from the Women's Healthy Eating and Living (WHEL) study.
      Physical activity was assessed using the International Physical Activity
      Questionnaire (IPAQ). A standardized questionnaire by the European Organization
      of Research and Treatment of Cancer Quality of Life and its breast cancer module
      (EORTC QLQ-C30/+BR-23) were applied to determine quality of life. Approximately
      29% of the cancer survivors were categorized as having healthy eating practices,
      34% had moderate eating practices and 37% had poor eating practices based on
      nutrition guidelines. The study found positive changes in the decreased intake of
      fast foods (90%), red meat (70%) and increased intake of fruits (85%) and
      vegetables (78%). Generally, breast cancer survivors with healthy eating
      practices had better global quality of life, social, emotional, cognitive and
      role functions. Result showed that only 12 women (12%) met the criteria for
      regular vigorous exercise, 22% had regular moderate-intensity exercise while the
      majority (65%) had low-intensity physical activity. Breast cancer survivors with
      higher level of physical activity had better emotional and cognitive functions.
      Healthy eating practices and physical activity can improve quality of life of
      cancer survivors. Health care professionals should promote good dietary habits
      and physical activity to improve survivors' health and quality of life.

PMID- 23534779
TI  - Clinico-pathological profile of lung cancer at AIIMS: a changing paradigm in
      India.
AB  - BACKGROUND: Lung cancer is one of the commonest and most lethal cancers
      throughout the world. The epidemiological and pathological profile varies among
      different ethnicities and geographical regions. At present adenocarcinoma is the
      commonest histological subtype of non-small cell lung cancer (NSCLC) in most of
      the Western and Asian countries. However, in India squamous cell carcinoma has
      been reported as the commonest histological type in most of the series. The aim
      of the study was to analyze the current clinico-pathological profile and survival
      of lung cancer at our centre. MATERIALS AND METHODS: We analyzed 434
      pathologically confirmed lung cancer cases registered at our centre over a period
      of three years. They were evaluated for their clinical and pathological profiles,
      treatment received and outcome. The available histology slides were reviewed by
      an independent reviewer. RESULTS: Median age was 55 years with a male:female
      ratio of 4.6:1. Some 68% of patients were smokers. There were 85.3% NSCLC and
      14.7% SCLC cases. Among NSCLCs, adenocarcinoma was the commonest histological
      subtype after the pathology review. Among NSCLC, 56.8% cases were of stage IV
      while among SCLC 71.8% cases had extensive stage disease. Some 29% of patients
      could not receive any anticancer treatment. The median overall and progression
      free survivals of the patients who received treatment were 12.8 and 7.8 months
      for NSCLC and 9.1 and 6.8 months for SCLC. CONCLUSIONS: This analysis suggests
      that adenocarcinoma may now be the commonest histological subtype also in India,
      provided a careful pathological review is done. Most of the patients present at
      advanced stage and outcome remains poor.

PMID- 23534780
TI  - EGFR antisense oligonucleotides encapsulated with nanoparticles decrease EGFR,
      MAPK1 and STAT5 expression in a human colon cancer cell line.
AB  - Epidermal growth factor receptor (EGFR) is over-expressed in several human
      cancers. This would suggest that inhibition of EGFR is a reasonable approach for
      cancer treatment. In this study we investigated EGFR blocking and its effects on
      the mediated signaling such as MAPK and STATb in HT29 cells. For this aim we used
      FITC-labeled EGFR antisense oligonucleotides encapsulated with PAMAM
      nanoparticles to inhibit EGFR expression. Cellular uptake of antisense was
      investigated by fluorescence microscopy and flow cytometry analysis. The effect
      of EGFR antisense on the expression of EGFR in HT29 cells was examined by real
      time PCR and Western blots, which showed that antisense encapsulated with PAMAM
      decreased the level of EGFR mRNA and protein. In addition, real time PCR results
      confirmed that EGFR inhibition had an effective role in the reduction of EGFR
      dependent downstream genes. In conclusion, EGFR antisense encapsulated with PAMAM
      nanoparticles down regulated EGFR and EGFR-mediated genes.

PMID- 23534781
TI  - Levels of serum trace elements in renal cell carcinoma cases.
AB  - Trace elements which are essential components of biological structures may also
      be toxic when present at levels above the amounts required for biological
      function. In our study, trace element levels were measured with furnace atomic
      absorption spectrophotometry in 33 newly diagnosed renal cell carcinoma cases
      (preoperative) and 32 healthy controls. When compared with the control group, it
      was found that the levels of cadmium (Cd), lead (Pb) were higher and the levels
      of zinc (Zn), iron (Fe) and manganese (Mn) were lower in the patient group. These
      changes may be important in the formation of renal cell carcinoma, a question
      which should be explored with postoperative comparative studies.

PMID- 23534782
TI  - Lentivirus-mediated silencing of rhomboid domain containing 1 suppresses tumor
      growth and induces apoptosis in hepatoma HepG2 cells.
AB  - Rhomboids were identified as the first intramembrane serine proteases about 10
      years ago. Since then, the study of the rhomboid protease family has blossomed.
      Rhomboid domain containing 1 (RHBDD1), highly- expressed in human testis,
      contains a rhomboid domain with unknown function. In the present study, we tested
      the hypothesis that RHBDD1 was associated with proliferation and apoptosis in
      hepatocellular carcinoma using recombinant lentivirus-mediated silencing of
      RHBDD1 in HepG2 cells. Our results showed that down-regulation of RHBDD1 mRNA
      levels markedly suppressed proliferation and colony formation capacity of HepG2
      human hepatoma cancer cells in vitro, and induced cell cycle arrest. We also
      found that RHBDD1 silencing could obviously trigger HepG2 cell apoptosis. In
      summary, it was demonstrated that RHBDD1 might be a positive regulator for
      proliferative and apoptotic characteristics of hepatocellular carcinoma.

PMID- 23534783
TI  - Human papilloma virus frequency and genotype distribution in a Turkish
      population.
AB  - OBJECTIVES: To determine human papillomavirus (HPV) frequency, genotypes and the
      relation between cervical smear results, risk factors and types in women living
      in Manisa, Turkey. MATERIALS AND METHODS: A total of 410 women were included in
      the study. Cervical specimens were obtained for linear array HPV genotyping and
      pathological testing. Conventional Pap test and Bethesda system were used for
      evaluation of cytology specimens. RESULTS: A total of 410 women with a mean age
      of 34.9 years were tested. A positive result of any HPV was found in 35 patients
      (8.5%). Among them, 26 different serotypes of HPV were identified and the most
      frequent type was HPV 16 (28.5%) followed by type 45 and 53 (11.4%). Patients
      were infected by 65.7% high risk, 11.4% probable high risk and 22.9% low risk HPV
      types. Multiple HPV positive results were found in 13 patients (37.1%). Patients
      with single partner, history of abnormal smear or condyloma had positive HPV
      results and this was statistically significant (p<0.05). Correlation analysis
      showed a statistically weak relation between positive HPV and abnormal smear
      results (r=0.120). CONCLUSIONS: Determining HPV types of genital HPV infections
      is important for epidemiological studies. We have found the rate of positive HPV
      as 8.5% which implies the need for extended screening programs in order to
      diagnose oncogenic HPV at an early stage.

PMID- 23534784
TI  - Construction and expression of an eukaryotic expression vector containing the
      IER3 gene.
AB  - BACKGROUND: More and more research indicate that the immediately early response
      gene 3 (IER3) is involved in many biological processes, such as apoptosis and
      immunoreaction, as well as viral infection, tumorigenesis and tumour progression.
      METHODS: Here we describe the construction of an eukaryotic expression vector
      containing IER3 gene and its expression in A549 cells as assessed through
      fluorescence microscopyand Western- blotting. RESULTS: Fluorescence detection
      displayed that GFP in cytoplasm was high during 48 and 72 hours post
      transfection. In addition, Western blotting showed significant increase in IER3
      gene expression in the transfected cells compared with controls. CONCLUSION: The
      recombinate plasmid expression vector was constructed successfully, which may
      provide a basis for further exploration of function of IER3 in lung cancer.

PMID- 23534785
TI  - Cost and effectiveness comparison of immediate colposcopy versus human
      papillomavirus DNA testing in management of atypical squamous cells of
      undetermined significance in Turkish women.
AB  - BACKGROUND: A small but significant proportion of cases with atypical squamous
      cells of undetermined significance (ASCUS) may harbour CIN 2-3, or even invasive
      carcinoma. Although immediate colposcopy, HPV-DNA testing or expectant management
      are three recommended options in ASCUS triage, a consensus does not currently
      exist on which one of these approaches is the most efficient. In this study, we
      aimed to compare the performance and cost of immediate colposcopy and colposcopy
      based on the human papillomavirus (HPV) testing for detecting histologically
      confirmed high-grade cervical intraepithelial neoplasia (CIN) in women with
      ASCUS. MATERIALS AND METHODS: Records of 594 women with an index Papanicolaou
      smear showing ASCUS were retrospectively analyzed. Women in the immediate
      colposcopy arm were referred directly to colposcopy (immediate colposcopy group,
      n=255) and those in the HPV triage arm were proceeded to colposcopy if the high
      risk HPV (hrHPV) test was positive (HPV triage group, n=339). High grade CIN
      (CIN2+) detection rate and treatment costs were compared between the groups.
      RESULTS: The detected rate of CIN2+ was higher in the HPV triage group compared
      to immediate colposcopy group (8% vs. 1.6%, p=0.011). In the HPV triage group,
      the total cost, cost per patient, and the cost for detecting one case of high
      grade CIN were higher than the immediate colposcopy group (p<0.001). CONCLUSIONS:
      In women with ASCUS cytology, HPV DNA testing followed by colposcopy is more
      costly than immediate colposcopy, but this approach is associated with a higher
      rate of CIN2+ detection. This findings suggest that HPV DNA testing combined with
      cervical cytology could reduce the referral rate to colposcopy.

PMID- 23534786
TI  - Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent
      chemoradiotherapy with or without adjuvant chemotherapy for locoregionally
      advanced nasopharyngeal carcinoma: meta-analysis of 1,096 patients from 11
      randomized controlled trials.
AB  - PURPOSE: To evaluate the efficacy and toxicity of induction chemotherapy followed
      by concurrent chemoradiotherapy (the treatment group) versus concurrent
      chemoradiotherapy with or without adjuvant chemotherapy (the control group) for
      locoregionally advanced nasopharyngeal carcinoma. METHODS: The search strategy
      included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet
      Web, Chinese Biomedical Database and Wanfang Database. We also searched reference
      lists of articles and the volumes of abstracts of scientific meetings. All
      randomized controlled trials were included for a meta-analysis performed with
      RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and
      Evaluation system (GRADE) was used to rate the level of evidence. RESULTS: Eleven
      studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20
      0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years
      overall survival, 3 years progression-free survival, 2 years loco-regional
      failure-free survival and 2 years distant metastasis failure-free survival. There
      were no treatment-related deaths in either group in the 11 studies. Risk ratios
      of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98
      (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4
      thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic
      and gastrointestinal toxicity, the most significant toxicities for patients.
      CONCLUSION: Compared with the control group, induction chemotherapy followed by
      concurrent chemoradiotherapy was well tolerated but could not significantly
      improve prognosis in terms of overall survival, loco-regional failure-free
      survival or distant metastasis failure-free survival.

PMID- 23534787
TI  - Electromagnetic field exposure and male breast cancer risk: a meta-analysis of 18
      studies.
AB  - BACKGROUND: The possibility that electromagnetic fields (EMF) exposure may
      increase male breast cancer risk has been discussed for a long time. However,
      arguments have been presented that studies limited by poor quality could have led
      to statistically significant results by chance or bias. Moreover, data fo the
      last 10 years have not been systematically summarized. METHODS AND RESULTS: To
      confirm any possible association, a meta-analysis was performed by a systematic
      search strategy. Totals of 7 case-control and 11 cohort studies was identified
      and pooled ORs with 95% CIs were used as the principal outcome measures. Data
      from these studies were extracted with a standard meta-analysis procedure and
      grouped in relation to study design, cut-off point, exposure assessment method,
      adjustment and exposure model. A statistical significant increased risk of male
      breast cancer with EMF exposure was defined (pooled ORs = 1.32, 95% CI = 1.14 
      1.52, P < 0.001), and subgroup analyses also showed similar results. CONCLUSIONS:
      This meta-analysis suggests that EMF exposure may be associated with the increase
      risk of male breast cancer despite the arguments raised.

PMID- 23534788
TI  - Clinical characteristics and treatment outcomes of patients with unresectable
      cholangiocarcinoma in Thailand: are there differences dependent on stent type?
AB  - Cholangiocarcinoma, though very rare in Western countries, is one of the
      commonest liver malignancies in Southeast Asia, especially in Thailand. More than
      half of the patients present with advanced stage disease. Given the poor
      treatment outcomes of adjuvant therapeutic options, many patients undergo only
      biliary drainage for palliative treatment. Clinical characteristics and treatment
      outcomes after biliary stenting were here analyzed for a total of 224
      unresectable cholangiocarcinoma cases, 58.9% in men. The mean age was 61.5 years.
      Hilar involvement was the most common location. The patients underwent biliary
      drainage using plastic and metallic stents equally, early stent occlusion being
      encountered in 21.4% and 10.7%, respectively. The median survival time was 4.93
      months for patients who received plastic and 5.87 months for patients who
      received metallic stents.

PMID- 23534789
TI  - Factors associated with Helicobacter pylori infection, results from a developing
      country - Pakistan.
AB  - BACKGROUND: It is known that blood group antigens are related to the development
      of peptic ulcer and gastric carcinoma. Infections due to H. pylori are most
      widespread among the developing regions due to poor standard of public health.
      This study sought to determine the association of H. pylori with ABO blood
      groups, age, gender, and smoking status among inpatients at a public sector
      hospital in Karachi. MATERIALS AND METHODS: A cross-sectional study was conducted
      at endoscopy suite at a public sector hospital in Karachi in the year 2011. All
      the symptomatic patients coming for upper GIT endoscopy were included in this
      study. RESULTS: Biopsy for histopathology was taken from 93 patients, with an age
      range from 15-65 years. Age group of 15 to 20 years was found to be associated
      with H. pylori infection but without significance (p-value 0.83). In all, 36
      (38.7%) turned out to be H. pylori positive with a significant male preponderance
      (p=0.04). Distribution of ABO blood groups in H. pylori positive group were
      A=31.4%, B=15.4%, AB=25.0% and O=53.7%, with a statistically significant link for
      blood group O (p=0.05) . Rhesus factor was also compared but significant
      relationship was evident (p-value 0.73). CONCLUSIONS: This study demonstrated
      that H. pylori infection can be related to ABO blood group, middle age persons
      and male gender. People of blood group O are more prone to develop infection
      related gastritis, ulcers, and even perforations, so they should be more cautious
      against transmission of the bacterium.

PMID- 23534790
TI  - Multicenter evaluation of patients with cutaneous malignant melanoma in Turkey:
      MELAS study.
AB  - BACKGROUND: Malignant melanoma is a cancer that demonstrates rapid progression
      and atypical clinically features with a poor prognosis. AIM: This study was
      performed to determine the clinical characteristics and treatment outcomes of
      patients with malignant melanoma in Turkey. METHODS: The medical records of 98
      patients between 2007- 2012 at our centers were retrieved from the patient
      registry. Overall survival (OS) was calculated using the Kaplan-Meier method.
      RESULTS: In our study, with the median follow-up of all patients with cutaneous
      MM of 46.3 months, the median OS rate of all cases was 43.6 months and 5-year OS
      was 48.6%. However, five-year OS rates of patients with localized disease (stage
      I-II) and node involvement (stage III) were 60.3% and 39.6%, respectively. The
      median OS of stage IV patients was 8.7 months and 1-year OS rate was 26.2%. We
      showed that advanced stage, male gender, and advanced age in all patients with MM
      were significant prognostic factors of OS. CONCLUSIONS: Compared with the results
      of current studies from Western countries, we found similar findings concerning
      demographical features, histological variables and survival analyses for our
      patients with cutaneous MM in Turkey.

PMID- 23534791
TI  - Factors predictive of treatment by Australian breast surgeons of invasive female
      breast cancer by mastectomy rather than breast conserving surgery.
AB  - BACKGROUND: The National Breast Cancer Audit Database of the Society of Breast
      Surgeons of Australia and New Zealand is used by surgeons to monitor treatment
      quality and for research. About 60% of early invasive female breast cancers in
      Australia are recorded. The objectives of this study are: (1) to investigate
      associations of socio-demographic, health-system and clinical characteristics
      with treatment of invasive female breast cancer by mastectomy compared with
      breast conserving surgery; and (2) to consider service delivery implications.
      MATERIALS AND METHODS: Bi-variable and multivariable analyses of associations of
      characteristics with surgery type for cancers diagnosed in 1998-2010. RESULTS: Of
      30,299 invasive cases analysed, 11,729 (39%) were treated by mastectomy as
      opposed to breast conserving surgery. This proportion did not vary by diagnostic
      year (p>0.200). With major city residence as the reference category, the relative
      rate (95% confidence limits) of mastectomy was 1.03 (0.99, 1.07) for women from
      inner regional areas and 1.05 (1.01, 1.10) for those from more remote areas. Low
      annual surgeon case load (<10) was predictive of mastectomy, with a relative rate
      of 1.08 (1.03, 1.14) when compared with higher case loads. Tumour size was also
      predictive, with a relative rate of 1.05 (1.01, 1.10) for large cancers (40+ mm)
      compared with smaller cancers (<30 mm). These associations were confirmed in
      multiple logistic regression analysis. CONCLUSIONS: Results confirm previous
      studies showing higher mastectomy rates for residents of more remote areas, those
      treated by surgeons with low case loads, and those with large cancers. Reasons
      require further study, including possible effects of surgeon and woman's choice
      and access to radiotherapy services.

PMID- 23534792
TI  - Risk factors for poorer breast cancer outcomes in residents of remote areas of
      Australia.
AB  - To investigate patient, cancer and treatment characteristics in females with
      breast cancer from more remote areas of Australia, to better understand reasons
      for their poorer outcomes, bi-variable and multivariable analyses were undertaken
      using the National Breast Cancer Audit database of the Society of Breast Surgeons
      of Australia and New Zealand. Results indicated that patients from more remote
      areas were more likely to be of lower socio- economic status and be treated in
      earlier diagnostic epochs and at inner regional and remote rather than major city
      centres. They were also more likely to be treated by low case load surgeons,
      although this finding was only of marginal statistical significance in
      multivariable analysis (p=0.074). Patients from more remote areas were less
      likely than those from major cities to be treated by breast conserving surgery,
      as opposed to mastectomy, and less likely to have adjuvant radiotherapy when
      having breast conserving surgery. They had a higher rate of adjuvant
      chemotherapy. Further monitoring will be important to determine whether breast
      conserving surgery and adjuvant radiotherapy utilization increase in rural
      patients following the introduction of regional cancer centres recently funded to
      improve service access in these areas.

PMID- 23534793
TI  - Clinicopathological features and localization of gastric cancers and their
      effects on survival in Turkey.
AB  - BACKGROUND: This study was designed to examine changing trends in localization of
      gastric cancer in Turkey in recent years. MATERIALS AND METHODS: A total of 796
      adult patients with newly diagnosed, histologically proven adenocarcinomas,
      treated and followed up at our oncology center between 2000-2011, were examined
      retrospectively. In all cases tumor localization were identified and recorded
      with clinicopathological features. RESULTS: The median age was 58 with a range
      between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1
      276) and median overall survival was also 12 months (11.5-12.4). There was a
      trend for a change in tumor localization from distal to proximal. Survival of
      patients was low with advanced T and N stage tumours. Positive surgical margins,
      lymphovascular invasion, perineural invasion, cardioesophageal localization were
      predisposition factors for metastatic disease in gastric cancer. There was no
      relation between age or sex and histopathological type of gastric cancer.
      CONCLUSIONS: There is a trend in our country for a change in gastric tumour
      localization from distal to proximal, with clear significance for treatment
      choices.

PMID- 23534794
TI  - Gene expression profiling of intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is ranked as one of the top five causes of
      cancer-related deaths. ICC in Thai patients is associated with infection with the
      liver fluke, Opisthorchis viverrini, but the molecular basis for development
      remains unclear. The present study employed a microarray approach to compare gene
      expression profiles of ICCs and normal liver tissues from the same patients
      residing in Northeast Thailand, a region with a high prevalence of liver fluke
      infection. In ICC samples, 2,821 and 1,361 genes were found to be significantly
      up- and down-regulated respectively (unpaired t-test, p<0.05; fold-change>2.0).
      For validation of the microarray results, 7 up-regulated genes (FXYD3, GPRC5A,
      CEACAM5, MUC13, EPCAM, TMC5, and EHF) and 3 down- regulated genes (CPS1, TAT, and
      ITIH1) were selected for confirmation using quantitative RT-PCR, resulting in
      100% agreement. The metallothionine heavy metal pathway contains the highest
      percentage of genes with statistically significant changes in expression. This
      study provides exon-level expression profiles in ICC that should be fruitful in
      identifying novel genetic markers for classifying and possibly early diagnosis of
      this highly fatal type of cholangiocarcinoma.

PMID- 23534795
TI  - Development and validation of a cancer awareness questionnaire for Malaysian
      undergraduate students of Chinese ethnicity.
AB  - OBJECTIVES: To describe the development and validation of a cancer awareness
      questionnaire (CAQ) based on a literature review of previous studies, focusing on
      cancer awareness and prevention. MATERIALS AND METHODS: A total of 388 Chinese
      undergraduate students in a private university in Kuala Lumpur, Malaysia, were
      recruited to evaluate the developed self-administered questionnaire. The CAQ
      consisted of four sections: awareness of cancer warning signs and screening
      tests; knowledge of cancer risk factors; barriers in seeking medical advice; and
      attitudes towards cancer and cancer prevention. The questionnaire was evaluated
      for construct validity using principal component analysis and internal
      consistency using Cronbach's alpha (alpha) coefficient. Test-retest reliability
      was assessed with a 10-14 days interval and measured using Pearson product-moment
      correlation. RESULTS: The initial 77-item CAQ was reduced to 63 items, with
      satisfactory construct validity, and a high total internal consistency
      (Cronbach's alpha=0.77). A total of 143 students completed the questionnaire for
      the test-retest reliability obtaining a correlation of 0.72 (p<0.001) overall.
      CONCLUSIONS: The CAQ could provide a reliable and valid measure that can be used
      to assess cancer awareness among local Chinese undergraduate students. However,
      further studies among students from different backgrounds (e.g. ethnicity) are
      required in order to facilitate the use of the cancer awareness questionnaire
      among all university students.

PMID- 23534796
TI  - Beliefs and behavior of Malaysia undergraduate female students in a public
      university toward breast self-examination practice.
AB  - BACKGROUND: Breast cancer is the most common cancer and the second principal
      cause of cancer deaths among women worldwide, including Malaysia. METHODS: A
      cross-sectional study was carried out among 262 female undergraduate students in
      University Putra Malaysia using a validated questionnaire which was developed for
      this study. RESULTS: The mean age of respondents was 22?2.3 years. Most of them
      were single (83.1%), Malay (42.3%) and 20.7% reported having a family history of
      breast cancer. Eighty-seven (36.7%) claimed they had practiced BSE. Motivation
      and self-efficacy of the respondents who performed BSE were significantly higher
      compared with women who did not (p<0.05).There was no association between BSE
      practice and demographic details (p<0.05). Logistic regression analysis indicated
      that women who perceived greater motivation (OR=1.089, 95%CI: 1.016-1.168) and
      had higher confidence of BSE (OR=1.076, 95%CI: 1.028-1.126) were more likely to
      perform the screening. CONCLUSIONS: The findings show that Malaysian young
      female's perception regarding breast cancer and the practice of BSE is low.
      Targeted education should be implemented to improve early detection of breast
      cancer.

PMID- 23534797
TI  - Social support and hopelessness in patients with breast cancer.
AB  - BACKGROUND: Patients with breast cancer can experience a feeling of hopelessness
      very deeply in the adjustment process, and the social support provided during
      this period can be effective in increasing the level of hope. The present study
      aimed to identify breast cancer patients' social support and hopelessness level.
      MATERIALS AND METHODS: The target population of this analytical study was all
      breast cancer patients (total of 85) who had treatment in the oncology department
      of a university hospital located in Adana/Turkey and who met the inclusion
      criteria. Data were collected through "Personal Information Form", "Beck
      Hopelessness Scale (BHS) " and "Multidimensional Scale of Perceived Social
      Support" (MSPSS). Analysis was performed using Shapiro Wilk, One Way ANOVA Welch,
      Student t-test, Mann Whitney U, and Kruskall Wallis tests. Homogeneity of
      variance was tested with the Levene, Bonferroni and Games Howell tests. Mean
      scores and standard deviation values are given as descriptive statistics.
      RESULTS: Average age of the participants with breast cancer is 48.6 ? 10.6. Of
      all the participants, 84.7% are married, 49.4% graduated from primary school,
      81.2% are housewives, and 82.4% had children. The participants' multidimensional
      perceived social support total scores were found to be high (57.41 ? 13.97) and
      hopelessness scale scores low (5.49 ? 3.80). There was a reverse, linear
      relationship between hopelessness scale scores and social support total scores
      (r=-0.259, p=0.017). A statistically significant relationship was found between
      hopelessness scores and education level and having children, occupation, income
      status, and education level of spouses (p<0.05). CONCLUSIONS: The present study
      indicates that hopelessness of the patients with breast cancer decreased with the
      increase in their social support. Therefore, activating patient social support
      systems is of importance in increasing their level of hope.

PMID- 23534798
TI  - Frequency of cigarette smoking among psychiatric inpatients evaluated by the
      Fagerstrom Test for Nicotine Dependence.
AB  - BACKGROUND: In this study our aim was to determine the rate of smoking in a
      sample of psychiatric in-patients with diagnoses of schizophrenia, bipolar
      disorder and major depression and to examine factors related to smoking status
      and the level of dependence in this population. MATERIALS AND METHODS: A total of
      160 people were included in this descriptive study. 80 were inpatients with
      schizophrenia, bipolar disorder and major depression and 80 people without any
      psychiatric diagnoses were included as a control group. The participants were
      interviewed face-to face using a semi-structured questionnaire and Fagerstrom
      Test for Nicotine Dependence was used to define smoking habits. RESULTS: The mean
      age of the participants was 37.24 ? 12.19 years ranging from 18 to 81 years,
      54.4% of the participants were (n=87) female, and 45.6% cases (n=73) were male.
      70% (n=56) of the patients and 55% of the control group were smoking and the
      difference was statistically significant (p<0.01). Total score of Fagerstrom Test
      for Nicotine Dependence in the patient group was statistically significantly
      higher than in the control group (p<0.01). CONCLUSIONS: In our sample, the
      frequency of cigarette smoking and nicotine dependence among psychiatric
      inpatients was high, posing a high risk for smoking related diseases including
      cancers; therefore there should be counseling on tobacco control and smoking
      cessation programming targeting this population.

PMID- 23534799
TI  - Chalkley microvessel but not lymphatic vessel density correlates with axillary
      lymph node metastasis in primary breast cancers.
AB  - This study aimed to investigate tumor microvessel density (MVD) and lymphatic
      vessel density (LVD) using the Chalkley method as predictive markers for the risk
      of axillary lymph node metastasis and their relationship to other
      clinicopathological parameters in primary breast cancer cases. Forty two node
      positive and eighty node-negative breast cancers were immunostained for CD34 and
      D2-40. MVD and LVD were counted by the Chalkley method at x400 magnification.
      There was a positive significant correlation of the MVD with the tumor size,
      coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In
      multivariate analysis, the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI
      3.47-115.6), lymphovascular invasion (OR 3.46, 95% CI 1.13-10.6), and associated
      DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillary lymph node
      metastasis. There was no significant relationship between LVD and axillary lymph
      node metastasis. However, D2-40 was a good lymphatic vessel marker to enhance the
      detection of lymphatic invasion compared to H and E staining. In conclusion, MVD
      by the Chalkley method, lymphovascular invasion and associated DCIS can be
      additional predictive factors for axillary lymph node metastases in breast
      cancer. No relationship was identified between LVD and clinicopathological
      variables, including axillary lymph node metastasis.

PMID- 23534800
TI  - Effect of screening on the risk estimates of socio demographic factors on
      cervical cancer - a large cohort study from rural India.
AB  - BACKGROUND: Prospective cohort studies to determine cofactors with oncogenic HPV-
      infections for cervical cancer are very rare from developing countries and such
      data are limited to the few screening trials. Large screening trials provide such
      data as a by product. Some of the cases are prevented by screening and do not
      surface as invasive cancers at all. Also, pre-invasive lesions are detected
      almost entirely by screening. Screening causes selection bias if attendance in or
      effectiveness of screening is correlated with the risk factors. The aim of this
      study was to quantify the influence of screening on risk factors for cervical
      cancer. MATERIALS AND METHODS: Our material stems from a rural cohort of 80,000
      women subjected to a randomised screening trial. The effect of screening on the
      incidence of cervix cancer was estimated with reference to socio-demographic and
      reproductive risk factors of cervical cancer. We compared these risks with the
      incidence of cancer in the randomised control population by the same determinants
      of risk. RESULTS: The results in the screening arm compared to the control arm
      showed that the women of low SES and young age were benefitting more than those
      of high SES and old age. The relative risk by age (30-39 vs 50-59) was 0.33 in
      the control arm and 0.24 in the screening arm. The relative risk by education
      (not educated vs educated) was 2.8 in the control arm and 1.8 in the screening
      arm. The previously married women did not benefit (incidence 113 and 115 per
      100,000 women years in control vs screening arms) whereas the effect was
      substantial in those married (86 vs 54). CONCLUSIONS: The results in controls
      were consistent with the general evidence, but results in attenders and
      nonattenders of the screening arm showed that screening itself and self-selection
      in attendance and effectiveness can influence the effect estimates of risk
      factors. The effect of cervical cancer screening programmes on the estimates of
      incidence of cervical cancer causes bias in the studies on etiology and,
      therefore, they should be interpreted with caution.

PMID- 23534801
TI  - Early detection of lung cancer risk using data mining.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death worldwide Therefore,
      identification of genetic as well as environmental factors is very important in
      developing novel methods of lung cancer prevention. However, this is a multi
      layered problem. Therefore a lung cancer risk prediction system is here proposed
      which is easy, cost effective and time saving. MATERIALS AND METHODS: Initially
      400 cancer and non-cancer patients' data were collected from different diagnostic
      centres, pre-processed and clustered using a K-means clustering algorithm for
      identifying relevant and non-relevant data. Next significant frequent patterns
      are discovered using AprioriTid and a decision tree algorithm. RESULTS: Finally
      using the significant pattern prediction tools for a lung cancer prediction
      system were developed. This lung cancer risk prediction system should prove
      helpful in detection of a person's predisposition for lung cancer. CONCLUSIONS:
      Most of people of Bangladesh do not even know they have lung cancer and the
      majority of cases are diagnosed at late stages when cure is impossible. Therefore
      early prediction of lung cancer should play a pivotal role in the diagnosis
      process and for an effective preventive strategy.

PMID- 23534802
TI  - Cytohistologic discrepancy of high-grade squamous intraepithelial lesions in
      Papanicolaou smears.
AB  - OBJECTIVES: To evaluate the frequency of cytohistologic discrepancy of high-grade
      squamous intraepithelial lesions (HSILs) in Pap smears and associated factors.
      METHODS: Medical records of 223 women with HSIL Pap smears who were treated at
      Thammasat University Hospital were reviewed. Data on age, parity, menopausal
      status, contraceptive use and colposcopic directed biopsy and loop
      electrosurgical excision procedure (LEEP) pathology results were recorded.
      RESULTS: Mean (SD) age of patients was 38.0 (9.4) years. The majority were
      premenopausal (86.5%) and multiparous (83.9%). Cytohistologic discrepancy between
      the Pap test and colposcopic-directed biopsy histology was 45.7% and that between
      the Pap test and LEEP histology was 29.5%. Fifty-four (24.2%) women had no high
      grade CIN on both colposcopic directed biopsy and LEEP. Nulliparity,
      postmenopausal status and having no oral contraceptive pills use were factors
      associated with cytohistologic discrepancy. CONCLUSION: The exact cytohistologic
      discrepancy rate was relatively high (24.2%). Factors associated with
      cytohistologic discrepancy were nulliparity and postmenopausal status and having
      no oral contraceptive pill use.

PMID- 23534803
TI  - Role of ultrasound in characterization of ovarian masses.
AB  - BACKGROUND: Ovarian cancer is the second most common malignancy in Pakistani
      women, accounting for 4% of all cancers in the female population. The aim of this
      study was to determine sensitivity, specificity, positive and negative predictive
      values and 95% confidence intervals for ultrasound in characterization of ovarian
      masses in patients presenting at public and private tertiary care hospitals in
      Karachi, Pakistan. MATERIALS AND METHODS: We adopted a cross-sectional analytical
      study design to retrospectively collect data from January 2009-11 from medical
      records of two tertiary care hospitals. Using a non-probability purposive
      sampling technique, we recruited a sample of 86 women aged between 15 and 85
      years fulfilling inclusion criteria with histopathologically proven ovarian
      masses presenting for an ultrasound examination in our radiology departments.
      RESULTS: Our retrospective data depicted sensitivity and specificity of
      ultrasound to be 90.7%, 95%CI (0.77, 0.97) and 91.4%, 95%CI (0.76, 0.98)
      respectively. Positive predictive value was 93%, 95%CI (0.79, 0.98) and negative
      predictive value was 89%, 95%CI (0.73, 0.96). A total of 78 ovarian masses were
      detected, out of which 42 were malignant and 36 were benign. CONCLUSIONS: Results
      of our study further reinforce the conclusion that ultrasound should be used as
      an initial modality of choice in the workup of every woman suspected of having an
      ovarian mass. It not only results in decreasing the mortality but also avoids
      unnecessary surgical interventions.

PMID- 23534804
TI  - Does zoledronic acid have additive effect on suppression of plasma estrogen
      levels?

PMID- 23534805
TI  - Correlation of microvessel density with nuclear pleomorphism, mitotic count and
      vascular invasion in breast and prostate cancers at preclinical and clinical
      levels.
AB  - BACKGROUND: Tumor angiogenesis correlates with recurrence and appears to be a
      prognostic factor for both breast and prostate cancers. In the present study, we
      aimed to investigate the correlation of microvessel density (MVD), a measure of
      angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in
      breast and prostate cancers at preclinical and clinical levels. METHODS: Samples
      from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma,
      established by BT-474 and PC-3 cell lines, respectively, and commensurate human
      paraffin-embedded blocks were obtained. To determine MVD, specimens were
      immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular
      invasion were determined using hematoxylin and eosin (HandE)-stained slides.
      RESULTS: MVD showed significant correlations with nuclear pleomorphism (r=0.68,
      P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate
      cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75,
      P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft
      model, a significant correlation was observed between MVD and vascular invasion
      (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly
      correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001;
      mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017;
      respectively). CONCLUSIONS: Our results demonstrate that MVD is correlated with
      nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical
      and clinical levels. This study therefore supports the predictive value of MVD in
      breast and prostate cancers.

PMID- 23534806
TI  - Improving safety-related knowledge, attitude and practices of nurses handling
      cytotoxic anticancer drug: pharmacists' experience in a general hospital,
      Malaysia.
AB  - BACKGROUND: An increasing trend of cytotoxic drug use, mainly in cancer
      treatment, has increased the occupational exposure among the nurses. This study
      aimed to assess the change of nurses' safety-related knowledge as well as
      attitude levels and subsequently to assess the change of cytotoxic drug handling
      practices in wards after a series of pharmacist-based interventions. MATERIALS
      AND METHODS: This prospective interventional study with a before and after design
      requested a single group of 96 nurses in 15 wards actively providing chemotherapy
      to answer a self-administered questionnaire. A performance checklist was then
      used to determine the compliance of all these wards with the recommended safety
      measures. The first and second assessments took 2 months respectively with a 9
      month intervention period. Pharmacist-based interventions included a series of
      technical, educational and administrative support measures consisting of the
      initiation of closed-system cytotoxic drug reconstitution (CDR) services,
      courses, training workshops and guideline updates. RESULTS: The mean age of
      nurses was 32.2?6.19 years. Most of them were female (93.8%) and married (72.9%).
      The mean knowledge score of nurses was significantly increased from 45.5?10.52 to
      73.4?8.88 out of 100 (p<0.001) at the end of the second assessment. Overall, the
      mean practice score among the wards was improved from 7.6?5.51 to 15.3?2.55 out
      of 20 (p<0.001). CONCLUSIONS: The pharmacist-based interventions improved the
      knowledge, attitude and safe practices of nurses in cytotoxic drug handling.
      Further assessment may help to confirm the sustainability of the improved
      practices.

PMID- 23534807
TI  - Quality of breast cancer early detection services conducted by well woman clinics
      in the district of Gampaha, Sri Lanka.
AB  - BACKGROUND: Breast cancer is the most common cancer diagnosed in females in Sri
      Lanka and early detection can lead to reduction in morbidity and mortality. AIM:
      To evaluate selected aspects of breast cancer early detection services
      implemented through well woman clinics (WWCs) in the Gampaha District. METHODS:
      The study consisted of two components. A retrospective descriptive arm assessed
      clinical breast examination (CBE) coverage of target age group women (TGW) of 35
      59 years in all the WWCs in Gampaha district over 2003- 2007. A cross sectional
      descriptive study additionally assessed quality of breast cancer early detection
      services. The Lot Quality Assurance Sampling (LQAS) technique was used to decide
      on the lot size and threshold values, which were computed as twenty and six
      clinics. Checklists were employed in assessing coverage, physical facilities and
      clinic activities. Client satisfaction on WWC services was assessed among 200 TGW
      attending 20 WWCs using an interviewer-administered questionnaire. RESULTS: CBE
      coverage in the Gampaha district increased only from 1.1-2.2% over 2003-2007.
      With regard to physical facilities, the number of clinics that were rated
      substandard varied between 7-18 (35- 90%). The items that were lacking included
      dust bins, notice boards, stationary, furniture and linen, and cleanliness of
      outside premises and toilets. With regard to clinic activities, punctuality of
      staff, late commencement of clinics, provision of health education, supervision,
      CBE and breast self-examination (BSE) were substandard in 7- 20 clinics (35
      100%). Client satisfaction for WWC services was 45.2% (IQR: 38.7-54.8%) and only
      11% had a score of >=70%, the cut off set for satisfaction. CONCLUSIONS: Breast
      cancer early detection service coverage in the Gampaha district remained low
      (2.2%) in 2007, 11 years after commencing WWCs. All 20 clinics were substandard
      for overall CBE and BSE.

PMID- 23534808
TI  - Diagnostic role of survivin in urinary bladder cancer.
AB  - BACKGROUND: Early diagnosis of carcinoma of bladder remains a challenge.
      Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is
      frequently activated in bladder carcinoma. The objective of this study was to
      investigate urinary survivin as a marker for diagnosis of urinary bladder.
      MATERIALS AND METHODS: We examined urinary survivin concentration in 28 healthy
      individuals, 46 positive controls and 117 cases of histologically proven TCC
      prior to transurethral resection, using ELISA, and compared values with findings
      for urinary cytology. RESULTS: Survivin was found to be significantly higher in
      the cancer group (P<0.05). A cut off value of 17.7 pg/ml was proposed, with an
      approximate sensitivity of 82.9% and specificity of 81.1% (P<0.0001), whereas
      urine cytology had a sensitivity of 66.7% and a specificity of 96.0%.
      CONCLUSIONS: Urinary survivin can be used as a non-invasive diagnostic biomarker
      for TCC bladder, both for primary and recurrent disease.

PMID- 23534809
TI  - GSTT1 null genotype distribution in the Kumaun region of northern India.
AB  - Glutathione S-transferases (GSTs) constitute a multigene family of
      multifunctional phase II metabolic enzymes. GSTT1, an important member of this
      group has a wide range of substrates including carcinogens. Total homozygous
      deletion or null genotype resulting in total lack of enzyme activity exists in
      populations for this enzyme. Since the null genotype may contribute to lower
      detoxification of carcinogens, this genotype is expected to increase cancer risk.
      The frequency of the GSTT1 null genotype is known to vary significantly among
      populations. However, little is known about its distribution in the hilly Kumaun
      region of northern India. Therefore, in this study, we determined the prevalence
      of the GSTT1 null polymorphism in the Kumaun popilation by conducting duplex PCR
      in 365 voluntary healthy individuals. The GSTT1 null genotype was detected in
      18.4% of the individuals. Since GSTs play significant role in xenobiotic
      metabolism, the present data on GSTT1 genotype distribution should contribute in
      understanding genetic association with cancer risk in this understudied
      population.

PMID- 23534810
TI  - Detection of p53 common intron polymorphisms in patients with gastritis lesions
      from Iran.
AB  - BACKGROUND: p53 alterations have been implicated in the development of many
      cancers, such as gastric cancer, but there is no evidence of p53 intron
      alterations in gastritis lesions. The aim of this study was to investigate the
      p53 intron alterations in gastritis along with p53 and mismatch repair protein
      expression and microsatellite status. MATERIALS AND METHODS: PCR-sequencing was
      conducted for introns 2-7 on DNA extracted from 97 paired samples of gastritis
      lesions and normal adjacent tissue. Abnormal accumulation of p53 and mismatch
      repair proteins was investigated using immunohistochemistry. In addition,
      microsatellite status was evaluated with reference to five mononucleotide
      markers. RESULTS: Gastritis cases included 41 males and 56 females in the age
      range of 15-83 years, 87.6% being H.pylori positive. IVS2+38, IVS3ins16 and
      IVS7+72 were the most polymorphic sites. Their minor allele frequency values were
      as follows: 0.38, 0.21 and 0.06, respectively. Samples with GG genotype at
      IVS2+38 and CT at IVS7+72 had no insertion. Moreover, most of the stable samples
      (91.9 %) had a G allele at IVS2+38. All of the samples were IHC negative for p53
      protein, microsatellite stable and expressed mismatch repair proteins. p53
      alterations were prominent in the HP+ group, but without statistical
      significance. CONCLUSIONS: According to our results, some p53 polymorphisms such
      as IVS2+38, IVS3ins16 and IVS7+72, because of their correlations together or with
      microsatellite status may contribute to gastritis development. However, so far
      effects on p53 expression and function remain unclear. Therefore, a comprehensive
      survey is needed to delineate their biological significance.

PMID- 23534811
TI  - Support Vector Machine based diagnostic system for thyroid cancer using
      statistical texture features.
AB  - OBJECTIVE: The aim of this study was to develop an automated computer-aided
      diagnostic system for diagnosis of thyroid cancer pattern in fine needle
      aspiration cytology (FNAC) microscopic images with high degree of sensitivity and
      specificity using statistical texture features and a Support Vector Machine
      classifier (SVM). MATERIALS AND METHODS: A training set of 40 benign and 40
      malignant FNAC images and a testing set of 10 benign and 20 malignant FNAC images
      were used to perform the diagnosis of thyroid cancer. Initially, segmentation of
      region of interest (ROI) was performed by region-based morphology segmentation.
      The developed diagnostic system utilized statistical texture features derived
      from the segmented images using a Gabor filter bank at various wavelengths and
      angles. Finally, the SVM was used as a machine learning algorithm to identify
      benign and malignant states of thyroid nodules. RESULTS: The SVMachieved a
      diagnostic accuracy of 96.7% with sensitivity and specificity of 95% and 100%,
      respectively, at a wavelength of 4 and an angle of 45. CONCLUSION: The results
      show that the diagnosis of thyroid cancer in FNAC images can be effectively
      performed using statistical texture information derived with Gabor filters in
      association with an SVM.

PMID- 23534812
TI  - Emotional maltreatment, peer victimization, and depressive versus anxiety
      symptoms during adolescence: hopelessness as a mediator.
AB  - Extensive comorbidity between depression and anxiety has driven research to
      identify unique and shared risk factors. This study prospectively examined the
      specificity of three interpersonal stressors (emotional abuse, emotional neglect,
      and relationally oriented peer victimization) as predictors of depressive versus
      anxiety symptoms in a racially diverse community sample of adolescents. We
      expanded on past research by examining hopelessness as a mediator of the
      relationships between these interpersonal stressors and symptoms. Participants
      included 225 adolescents (55% African American; 59% female; M age = 12.84 years)
      who completed measures at baseline (Time 1) and two follow-up assessments (Times
      2 and 3). Symptoms of depression and anxiety (social, physical, total) were
      assessed at Time 1 and Time 3, whereas intervening emotional maltreatment, peer
      victimization, and hopelessness were assessed at Time 2. Hierarchical linear
      regressions indicated that emotional abuse was a nonspecific predictor of
      increases in both depressive symptoms and symptoms of social, physical, and total
      anxiety, whereas relationally oriented peer victimization predicted depressive
      symptoms specifically. Emotional neglect did not predict increases in depressive
      or anxiety symptoms. In addition, hopelessness mediated the relationships between
      emotional abuse and increases in symptoms of depression and social anxiety. These
      findings suggest that emotional abuse and relationally oriented peer
      victimization are interpersonal stressors that are relevant to the development of
      internalizing symptoms in adolescence and that hopelessness may be one mechanism
      through which emotional abuse contributes to an increased risk of depression and
      social anxiety.

PMID- 23534813
TI  - Heat-mediated enrichment of alpha-synuclein from cells and tissue for assessing
      post-translational modifications.
AB  - alpha-Synuclein (alpha-syn) is the major component of Lewy bodies, a pathological
      hallmark of Parkinson's disease and other synucleinopathies. The characterization
      of alpha-syn post-translational modifications (PTMs), thought to interfere with
      its aggregation propensity and cellular signaling, has been limited by the
      availability of extraction methods of endogenous protein from cells and tissues,
      and by the availability of antibodies toward alpha-syn PTMs. Here, by taking
      advantage of alpha-syn thermostability, we applied a method to achieve high
      enrichment of soluble alpha-syn both from cultured cells and brain tissues
      followed by proteomics analysis. Using this approach, we obtained 98% alpha-syn
      sequence coverage in a variety of model systems, including a transgenic mouse
      model of PD, and validated the strategy by identifying previously described PTMs
      such as phosphorylation and N-terminal acetylation. Our findings demonstrate that
      this procedure overcomes existing technical limitations and can be used to
      facilitate the systematic study of alpha-syn PTMs, thereby enabling the
      clarification of their role under physiological and pathological conditions.
      Ultimately, this approach may enable the development of novel biomarkers and
      strategies for therapeutic intervention in synucleinopathies.

PMID- 23534814
TI  - Food shopping behaviours and exposure to discrimination.
AB  - OBJECTIVE: The present study examined food shopping behaviours, particularly
      distance to grocery shop, and exposure to discrimination. DESIGN: Cross-sectional
      observational study utilizing data from a community survey, neighbourhood food
      environment observations and the decennial census. SETTING: Three communities in
      Detroit, Michigan, USA. SUBJECTS: Probability sample of 919 African-American,
      Latino and white adults in 146 census blocks and sixty-nine census block groups.
      RESULTS: On average, respondents shopped for groceries 3.1 miles (4.99 km) from
      home, with 30.9 % shopping within 1 mile (1.61 km) and 22.3 % shopping more than
      5 miles (8.05 km) from home. Longer distance to shop was associated with being
      younger, African-American (compared with Latino), a woman, higher socio-economic
      status, lower satisfaction with the neighbourhood food environment, and living in
      a neighbourhood with higher poverty, without a large grocery store and further
      from the nearest supermarket. African-Americans and those with the lowest incomes
      were particularly likely to report unfair treatment at food outlets. Each mile
      (1.61 km) increase in distance to shop was associated with a 7 % increase in the
      odds of unfair treatment; this relationship did not differ by race/ethnicity.
      CONCLUSIONS: The study suggests that unfair treatment in retail interactions
      warrants investigation as a pathway by which restricted neighbourhood food
      environments and food shopping behaviours may adversely affect health and
      contribute to health disparities. Efforts to promote 'healthy' and equitable food
      environments should emphasize local availability and affordability of a range of
      healthy food products, as well as fair treatment while shopping regardless of
      race/ethnicity or socio-economic status.

PMID- 23534816
TI  - Detection of novel genetic variation in autosomal dominant retinitis pigmentosa.
AB  - We explored an approach to detect disease-causing sequence variants in 448
      candidate genes from five index cases of autosomal dominant retinitis pigmentosa
      (adRP) by sequence DNA capture and next-generation DNA sequencing (NGS).
      Detection of sequence variants was carried out by sequence capture NimbleGen and
      NGS in a SOLiD platform. After filtering out variants previously reported in
      genomic databases, novel potential adRP-causing variants were validated by
      dideoxy capillary electrophoresis (Sanger) sequencing and co-segregation in the
      families. A total of 55 novel sequence variants in the coding or splicing regions
      of adRP candidate genes were detected, 49 of which were confirmed by Sanger
      sequencing. Segregation of these variants in the corresponding adRP families
      showed three variants present in all the RP-affected members of the family. A
      novel mutation, p.L270R in IMPDH1, was found to be disease causing in one family.
      In another family a variant, p.M96T in the NRL gene was detected; this variant
      was previously reported as probably causing adRP. However, the previously
      reported p.A76V mutation in NRL as a cause of RP was excluded by co-segregation
      in the family. We discuss the benefits and limitations of our approach in the
      context of mutation detection in adRP patients. 

PMID- 23534817
TI  - Prospective radial artery study following induction of reactive hyperemia looking
      at degree of diameter growth in healthy subjects.
AB  - OBJECTIVES: This "proof of concept" study sought to determine the magnitude of
      radial artery diameter change in 20 healthy subjects by induction of flow
      mediation dilatation (FMD) via reactive hyperemia. BACKGROUND: Transradial access
      in the cardiac catheterization laboratory is becoming more commonplace due to
      lower bleeding complications and increase in patient comfort. However, access to
      the radial artery can be challenging due to small vessel size. We sought to
      examine whether FMD can be used to increase radial artery diameter, potentially
      allowing improved transradial access. METHODS: We obtained baseline radial artery
      diameter via a high frequency ultrasound probe on 20 healthy subjects. A standard
      reactive hyperemia protocol was employed in the right arm, followed by successive
      measurements of the subject's radial artery at pre-specified intervals. Radial
      artery diameter measurements were performed offline by the sonographer and also a
      blinded reader to which agreement was sought. RESULTS: We found a mean increase
      in radial artery size of 0.48 +/- 0.13 mm at peak reactive hyperemic states. This
      correlated to a mean increase in overall radial artery diameter of 21.7 +/- 6.7%.
      The median time to peak dilation was 30 seconds (95% CI; 15-45 seconds), and the
      median duration of maximal dilation was 60 seconds (95% CI; 45-75 seconds).
      CONCLUSIONS: Among healthy subjects, we demonstrated a mean maximal increase in
      radial artery diameter of 21.7 +/- 6.7% via FMD. This finding supports the notion
      that radial artery diameter can be increased noninvasively via a reactive
      hyperemia protocol.

PMID- 23534818
TI  - Intonation influences how children and adults interpret sarcasm.
AB  - Adults distinguish sarcasm from literal language according to intonation
      involving a reduction in fundamental frequency (F0). We examined whether
      children's and adults' interpretation of a sarcastic speaker's belief, attitude,
      and humor was affected by degree of F0 reduction by presenting five- to six-year
      olds and adults with sarcastic and literal criticisms with a small, medium, or
      large mean F0 reduction. Children and adults were more accurate in attributing
      the speaker's belief and intent for sarcastic criticisms for large F0 reductions
      compared to small reductions. These results show that F0 reduction is a helpful
      cue to sarcasm interpretation for both children and adults.

PMID- 23534819
TI  - Isomer-specific LC/MS and LC/MS/MS profiling of the mouse serum N-glycome
      revealing a number of novel sialylated N-glycans.
AB  - Mice are the premier mammalian models for studies of human physiology and
      disease, bearing extensive biological similarity to humans with far fewer
      ethical, economic, or logistic complications. To facilitate glycomic studies
      based on the mouse model, we comprehensively profiled the mouse serum N-glycome
      using isomer-specific nano-LC/MS and -LC/MS/MS. N-Glycans were identified by
      accurate mass MS and structurally elucidated by MS/MS. Porous graphitized carbon
      nano-LC was able to separate out nearly 300 N-linked glycan compounds (including
      isomers) from just over 100 distinct N-linked glycan compositions. Additional
      MS/MS structural analysis was performed on a number of novel N-glycans, revealing
      the structural characteristics of modifications such as dehydration, O
      acetylation, and lactylation. Experimental findings were combined with known
      glycobiology to generate a theoretical library of all biologically possible mouse
      serum N-glycan compositions. The library may be used for automated identification
      of complex mixtures of mouse N-glycans, with possible applications to a wide
      range of mouse-related research endeavors, including pharmaceutical drug
      development and biomarker discovery. 

PMID- 23534815
TI  - Stability of hepatitis C virus (HCV) RNA levels among interferon-naive HIV/HCV
      coinfected individuals treated with combination antiretroviral therapy.
AB  - OBJECTIVES: Infection with hepatitis C virus (HCV) is a major cause of chronic
      liver disease. High HCV RNA levels have been associated with poor treatment
      response. This study aimed to examine the natural history of HCV RNA in
      chronically HCV/HIV-coinfected individuals. METHODS: Mixed models were used to
      analyse the natural history of HCV RNA changes over time in HIV-positive patients
      with chronic HCV infection. RESULTS: A total of 1541 individuals, predominantly
      White (91%), male (73%), from southern (35%) and western central Europe (23%) and
      with HCV genotype 1 (58%), were included in the analysis. The median follow-up
      time was 5.0 years [interquartile range (IQR) 2.8 to 8.3 years]. Among patients
      not on combination antiretroviral therapy (cART), HCV RNA levels increased by a
      mean 27.6% per year [95% confidence interval (CI) 6.1-53.5%; P = 0.0098]. Among
      patients receiving cART, HCV RNA levels were stable, increasing by a mean 2.6%
      per year (95% CI -1.1 to 6.5%; P = 0.17). Baseline HCV RNA levels were 25.5%
      higher (95% CI 8.8 to 39.1%; P = 0.0044) in individuals with HCV genotype 1
      compared with HCV genotypes 2, 3 and 4. A 1 log HIV-1 RNA copies/mL increase in
      HIV RNA was associated with a 10.9% increase (95% CI 2.3 to 20.2%; P = 0.012) in
      HCV RNA. CONCLUSIONS: While HCV RNA levels increased significantly in patients
      prior to receiving cART, among those treated with cART HCV RNA levels remained
      stable over time.

PMID- 23534820
TI  - von Willebrand factor contributes to longer half-life of PEGylated factor VIII in
      vivo.
AB  - PEGylation of B-domain deleted factor VIII (PEG-FVIII-BDD) prolongs the half-life
      of the molecule by approximately twofold in animals (Mei et al., Blood 2010; 116:
      270). To investigate the role of von Willebrand factor (vWF) in the catabolism of
      PEG-FVIII-BDD in vivo, a FVIII-BDD mutant (F8V), which is incapable of binding
      vWF, was generated by deleting the vWF-binding region in the a3 domain of FVIIII
      BDD. F8V was expressed, purified and PEGylated by site-specific conjugation. The
      biochemical and biological properties of F8V and PEGylated F8V (PEG-F8V) were
      evaluated in vitro and in vivo. The specific activity of purified F8V by a
      chromogenic assay was similar to FVIII-BDD and PEGylation had minimal impact on
      the specific activity of F8V in this assay. Analysis by Biacore indicated that
      both F8V and PEG-F8V display greatly reduced vWF binding in vitro.
      Pharmacokinetic studies in FVIII knockout (HaemA) mice showed that the terminal
      half-life (T1/2 ) of F8V was dramatically reduced relative to FVIII-BDD (0.6 h
      vs. 6.03 h). PEGylation of F8V promoted a significant increase in T1/2 , although
      PEGylation did not fully compensate for the loss in vWF binding. PEG-F8V showed a
      shorter T1/2 than PEG-FVIII-BDD both in HaemA mice (7.7 h vs. 14.3 h) and in
      Sprague-Dawley male rats (2.0 +/- 0.3 h vs. 6.0 +/- 0.5 h). These data
      demonstrated that vWF contributes to the longer T1/2 of PEG-FVIII-BDD.
      Furthermore, this suggests that the clearance of the FVIII:vWF complex, through
      vWF receptors, is not the sole factor which places an upper limit on the duration
      of PEG-FVIII circulation in plasma.

PMID- 23534821
TI  - Soret coefficient in nonionic microemulsions: concentration and structure
      dependence.
AB  - Here we investigate the thermal diffusion behavior of the nonionic microemulsion
      water/n-decane/pentaethylene glycol monododecyl ether (C12E5). We study the
      dependence of the Soret coefficient on the structure and composition by infrared
      thermal diffusion Rayleigh scattering. The form and size of the microemulsion
      structure is characterized by dynamic light scattering and small angle neutron
      scattering. The system was examined in the one-phase region between the
      emulsification failure boundary and the near critical boundary, where oil swollen
      nanostructures stabilized by an amphiphilic surfactant film are dispersed in a
      continuous water phase. The size and shape of these structures as well as the
      interfacial properties of microemulsions can be varied by changing temperature
      and composition, which allows a systematic study of their influence on the
      thermal diffusion properties. In addition, we analyze the relationship between
      the Soret coefficient and the temperature dependence of the interfacial tension
      as proposed by A. Parola and R. Piazza (Eur. Phys. J. E 2004, 15, 255-263) and
      find reasonable agreement for spherical microemulsion droplets.

PMID- 23534822
TI  - Avoiding magnetochemical overparametrization, exemplified by one-dimensional
      chains of hexanuclear iron(III) pivalate clusters.
AB  - One-dimensional chain coordination polymers based on hexanuclear iron(III)
      pivalate building blocks and 1,4-dioxane (diox) or 4,4'-bipyridine (4,4'-bpy)
      bridging ligands, [Fe6O2(O2CH2)(O2CCMe3)12(diox)]n (1) and
      [Fe6O2(O2CH2)(O2CCMe3)12(4,4'-bpy)]n (2), showcase the utility of the angular
      overlap model, implemented in the program wxJFinder, in the predictive
      identification of the relative role of intra- and intercluster coupling.

PMID- 23534823
TI  - ADAR-related activation of adenosine-to-inosine RNA editing during regeneration.
AB  - Urodele amphibians possess an amazing regenerative capacity that requires the
      activation of cellular plasticity in differentiated cells and progenitor/stem
      cells. Many aspects of regeneration in Urodele amphibians recapitulate
      development, making it unlikely that gene regulatory pathways which are essential
      for development are mutually exclusive from those necessary for regeneration. One
      such post-transcriptional gene regulatory pathway, which has been previously
      shown to be essential for functional metazoan development, is RNA editing. RNA
      editing catalyses discrete nucleotide changes in RNA transcripts, creating a
      molecular diversity that could create an enticing connection to the activated
      cellular plasticity found in newts during regeneration. To assess whether RNA
      editing occurs during regeneration, we demonstrated that GABRA3 and ADAR2 mRNA
      transcripts are edited in uninjured and regenerating tissues. Full open-reading
      frame sequences for ADAR1 and ADAR2, two enzymes responsible for adenosine-to
      inosine RNA editing, were cloned from newt brain cDNA and exhibited a strong
      resemblance to ADAR (adenosine deaminase, RNA-specific) enzymes discovered in
      mammals. We demonstrated that ADAR1 and ADAR2 mRNA expression levels are
      differentially expressed during different phases of regeneration in multiple
      tissues, whereas protein expression levels remain unaltered. In addition, we have
      characterized a fascinating nucleocytoplasmic shuttling of ADAR1 in a variety of
      different cell types during regeneration, which could provide a mechanism for
      controlling RNA editing, without altering translational output of the editing
      enzyme. The link between RNA editing and regeneration provides further insights
      into how lower organisms, such as the newt, can activate essential molecular
      pathways via the discrete alteration of RNA sequences.

PMID- 23534824
TI  - Libyan Journal of Medicine among top journals in African and Arab countries.

PMID- 23534826
TI  - Antifreeze (glyco)protein mimetic behavior of poly(vinyl alcohol): detailed
      structure ice recrystallization inhibition activity study.
AB  - This manuscript reports a detailed study on the ability of poly(vinyl alcohol) to
      act as a biomimetic surrogate for antifreeze(glyco)proteins, with a focus on the
      specific property of ice-recrystallization inhibition (IRI). Despite over 40
      years of study, the underlying mechanisms that govern the action of biological
      antifreezes are still poorly understood, which is in part due to their limited
      availability and challenging synthesis. Poly(vinyl alcohol) (PVA) has been shown
      to display remarkable ice recrystallization inhibition activity despite its major
      structural differences to native antifreeze proteins. Here, controlled radical
      polymerization is used to synthesize well-defined PVA, which has enabled us to
      obtain the first quantitative structure-activity relationships, to probe the role
      of molecular weight and comonomers on IRI activity. Crucially, it was found that
      IRI activity is "switched on" when the polymer chain length increases from 10 and
      20 repeat units. Substitution of the polymer side chains with hydrophilic or
      hydrophobic units was found to diminish activity. Hydrophobic modifications to
      the backbone were slightly more tolerated than side chain modifications, which
      implies an unbroken sequence of hydroxyl units is necessary for activity. These
      results highlight that, although hydrophobic domains are key components of IRI
      activity, the random inclusion of addition hydrophobic units does not guarantee
      an increase in activity and that the actual polymer conformation is important.

PMID- 23534825
TI  - A combination of plasma DAO and citrulline levels as a potential marker for acute
      mesenteric ischemia.
AB  - INTRODUCTION: There is no valid and reliable diagnostic test for early diagnosis
      of acute mesenteric ischemia (AMI). The aim of this study was to measure the
      plasma levels of diamine oxidase (DAO) and citrulline in AMI to gain insight into
      its early diagnosis. MATERIAL AND METHODS: A total of 21 Wistar albino rats were
      divided into three groups, that is, control group, short-term ischemia group, and
      prolonged ischemia group. The superior mesenteric artery was occluded for 15 min
      in the short-term ischemia group and for 12 h in the prolonged ischemia group.
      Twelve hours later, the experiment was terminated and plasma DAO and citrulline
      levels were measured. Intestinal tissue was evaluated for the histopathological
      changes. RESULTS: Compared to the control group, the short-term and prolonged
      ischemia groups showed significant increases in the plasma levels of DAO, whereas
      the plasma citrulline levels decreased significantly. Prolonged ischemia caused a
      larger increase in the plasma DAO levels and a larger decrease in the plasma
      citrulline levels compared to the short-term ischemia (p=0.011 and p=0.021,
      respectively). Intestinal damage was shown to develop more in the prolonged
      ischemia group (p=0.001). CONCLUSION: In the early period of AMI, the plasma DAO
      levels increase while citrulline levels decrease, and the extent of these changes
      depends on the duration of ischemia.

PMID- 23534827
TI  - Generalized structural description of calcium-sodium aluminosilicate hydrate
      gels: the cross-linked substituted tobermorite model.
AB  - Structural models for the primary strength and durability-giving reaction product
      in modern cements, a calcium (alumino)silicate hydrate gel, have previously been
      based solely on non-cross-linked tobermorite structures. However, recent
      experimental studies of laboratory-synthesized and alkali-activated slag (AAS)
      binders have indicated that the calcium-sodium aluminosilicate hydrate [C-(N)-A-S
      H] gel formed in these systems can be significantly cross-linked. Here, we
      propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked
      and non-cross-linked tobermorite-based structures (the cross-linked substituted
      tobermorite model, CSTM), which can more appropriately describe the spectroscopic
      and density information available for this material. Analysis of the phase
      assemblage and Al coordination environments of AAS binders shows that it is not
      possible to fully account for the chemistry of AAS by use of the assumption that
      all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due
      to the structural constraints of the gel. Application of the CSTM can for the
      first time reconcile this information, indicating the presence of an additional
      activation product that contains highly connected four-coordinated silicate and
      aluminate species. The CSTM therefore provides a more advanced description of the
      chemistry and structure of calcium-sodium aluminosilicate gel structures than
      that previously established in the literature.

PMID- 23534828
TI  - How do nurse practitioners in acute care affect perceptions of team
      effectiveness?
AB  - AIMS AND OBJECTIVES: To describe how acute care nurse practitioners affect
      perceptions of team effectiveness. BACKGROUND: Acute care nurse practitioners
      provide safe and effective care to patients. There is limited evidence of the
      effects of acute care nurse practitioner roles on healthcare teams, and many of
      the findings are contradictory. Research is lacking to describe how nurse
      practitioners affect perceptions of team effectiveness. DESIGN: A descriptive
      multiple-case study undertaken in two university-affiliated teaching hospitals in
      Canada. METHODS: Data were collected from March-May 2009. Data sources included
      interviews (n = 59), time and motion study, non-participant observations,
      documents and field notes. Interviews were conducted individually or in groups
      using a semi-structured interview guide. Data were analysed within and across the
      cases to identify similarities and differences in perceptions of team
      effectiveness. RESULTS: Team members believed the nurse practitioners improved
      the team's effectiveness. They identified six team processes they believed were
      improved by the addition of the nurse practitioners to the teams. The processes
      included decision-making, communication, cohesion, care coordination, problem
      solving and focus on patients and families. DISCUSSION: The study contributes to
      our understanding of how nurse practitioners affect perceptions of team
      effectiveness. Improved team communication and care coordination were believed to
      be particularly important. Nurse practitioner can facilitate patient- and family
      centred care in healthcare teams. CONCLUSION: Nurse practitioners improve
      perceptions of team effectiveness. Further work is needed in different contexts
      and with patients and families to determine their perceptions of team
      effectiveness. RELEVANCE TO CLINICAL PRACTICE: The nurse practitioner role was
      believed to be particularly important to improve team communication and care
      coordination. This constitutes an added value of acute care nurse practitioners
      roles in healthcare teams. Nurse practitioner roles contribute to patient-centred
      care and can improve the quality and safety of the care provided to patients and
      families.

PMID- 23534829
TI  - Visible-light-induced oxygenation of benzene by the triplet excited state of 2,3
      dichloro-5,6-dicyano-p-benzoquinone.
AB  - Photocatalytic oxygenation of benzene to phenol occurs under visible-light
      irradiation of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) in an oxygen
      saturated acetonitrile solution of benzene and tert-butyl nitrite. The
      photocatalytic reaction is initiated by photoinduced electron transfer from
      benzene to the triplet excited state of DDQ.

PMID- 23534830
TI  - Dye-sensitization-induced visible-light reduction of graphene oxide for the
      enhanced TiO2 photocatalytic performance.
AB  - The reduction of graphene oxide (GO) with a large-scale production has been
      demonstrated to be one of the key steps for the preparation of graphene-based
      composite materials with various potential applications. Therefore, it is highly
      required to develop a facile, green, and environmentally friendly route for the
      effective reduction of GO. In this study, a new and effective reduced method of
      GO nanosheets, based on the dye-sensitization-induced visible-light reduction
      mechanism, was developed to prepare reduced GO (rGO) and graphene-based TiO2
      composite in the absence of any additional reducing agents. It was found that the
      dye-sensitization-induced reduction process of GO was accompanied with the
      formation of TiO2-rGO composite nanostructure. The photocatalytic experimental
      results indicated that the resultant TiO2-rGO nanocomposites exhibited
      significantly higher photocatalytic performance than pure TiO2 because of a rapid
      separation of photogenerated electrons and holes by the rGO cocatalyst.

PMID- 23534831
TI  - Effects of video feedback on early coercive parent-child interactions: the
      intervening role of caregivers' relational schemas.
AB  - We examined the effect of adding a video feedback intervention component to the
      assessment feedback session of the Family Check-Up (FCU) intervention (Dishion &
      Stormshak, 2007). We hypothesized that the addition of video feedback procedures
      during the FCU feedback at child age 2 would have a positive effect on
      caregivers' negative relational schemas of their child, which in turn would
      mediate reductions in observed coercive caregiver-child interactions assessed at
      age 5. We observed the caregiver-child interaction videotapes of 79 high-risk
      families with toddlers exhibiting clinically significant problem behaviors. A
      quasi-random sample of families was provided with direct feedback on their
      interactions during the feedback session of the FCU protocol. Path analysis
      indicated that reviewing and engaging in feedback about videotaped age 2
      assessment predicted reduced caregivers' negative relational schemas of the child
      at age 3, which acted as an intervening variable on the reduction of observed
      parent-child coercive interactions recorded at age 5. Video feedback predicted
      improved family functioning over and above level of engagement in the FCU in
      subsequent years, indicating the important incremental contribution of using
      video feedback procedures in early family-based preventive interventions for
      problem behaviors. Supportive video feedback on coercive family dynamics is an
      important strategy for promoting caregiver motivation to reduce negative
      attributions toward the child, which fuel coercive interactions. Our study also
      contributes to the clinical and research literature concerning coercion theory
      and effective intervention strategies by identifying a potential mechanism of
      change.

PMID- 23534833
TI  - Anti-ABCG2 monoclonal antibody in combination with paclitaxel nanoparticles
      against cancer stem-like cell activity in multiple myeloma.
AB  - AIM: To investigate the effects of anti-ABCG2 monoclonal antibodies (mAbs) in
      combination with paclitaxel iron oxide nanoparticles (PTX-NPs) on CD138(-)CD34(-)
      multiple myeloma (MM) cancer stem cells (CSCs) in JJN3 cells. MATERIALS &
      METHODS: PTX-NPs were prepared using the hydrophobic interaction of the
      polyoxypropylene chain and oleic acid on the surface of iron oxide NPs and were
      targeted to the ABCG2 transporter overexpressing MM CSCs with mAbs. RESULTS: The
      data showed that MM CSCs have strong drug resistance and tumorigenicity compared
      with non-MM CSCs. PTX-NPs combined with mAbs led to a significant reduction in
      the tumor volume, a visible alleviation of lytic bone lesions and a markedly
      increased survival rate in contrast to using a single agent in MM CSCs when it
      was transplanted to nonobese diabetic/severe combined immunodeficiency mice.
      CONCLUSION: This study is the first to report on the anti-MM CSC activity by PTX
      NPs as a single agent or used together with anti-ABCG2 mAbs to treat MM. These
      findings provide a rationale for future clinical trials.

PMID- 23534832
TI  - Ferumoxytol: a new, clinically applicable label for stem-cell tracking in
      arthritic joints with MRI.
AB  - AIM: To develop a clinically applicable MRI technique for tracking stem cells in
      matrix-associated stem-cell implants, using the US FDA-approved iron supplement
      ferumoxytol. MATERIALS & METHODS: Ferumoxytol-labeling of adipose-derived stem
      cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral
      defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or
      unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell
      implant. The signal-to-noise ratio of different matrix-associated stem-cell
      implant was compared with t-tests and correlated with histopathology. RESULTS: An
      incubation concentration of 500 ug iron/ml ferumoxytol and 10 ug/ml protamine
      sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired
      ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated
      significantly lower signal-to-noise ratio values compared with unlabeled controls
      (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow
      dilution of the iron label over time. CONCLUSION: Ferumoxytol can be used for in
      vivo tracking of stem cells with MRI.

PMID- 23534835
TI  - Feasibility study of asset mapping with children: identifying how the community
      environment shapes activity and food choices in Alexander First Nation.
AB  - INTRODUCTION: It is estimated that First Nations children living on reserves are
      4.5 times more likely to be obese than Canadian children in general. Many First
      Nations children living on reserves have limited healthy food and physical
      activity options. Understanding how community factors contribute to First Nations
      children's lifestyle choices is an understudied area of research. Furthermore,
      rarely has health research elicited First Nations children's perspectives of
      their communities. The purpose of this study was to understand the external
      behavior-shaping factors that influence the lifestyle behaviors of First Nations'
      children. Asset mapping with children was used to understand how community
      resources impacted children's activity and eating options. METHODS: Alexander
      First Nation is in central Alberta. Asset mapping was one component of a research
      project in the community to identify risk factors for children developing
      diabetes. Participants were a convenience sample of two high school students
      working at the local health centre and seven grade six children. Maps,
      photographs, and a tour of the town site enabled participants to identify places
      and spaces where they were active or could obtain food. For each of these assets,
      a description of how it was used and how it could be modified for better usage
      was derived from notes and transcripts using content analysis. Assets were
      grouped into usage categories, which were then mapped onto a layout of the
      community and presented at a community meeting to address childhood obesity.
      RESULTS: Twenty-five places and spaces were identified as being activity or food
      related. Breakfast and/or lunch, concession foods (snack foods, eg chocolate
      bars, potato crisps) were obtained at school; meals and snack foods where
      cultural gatherings occur; and snack foods at the local store. Healthy food
      choices were limited. Children and youth were active at different locations in
      town, with only two spaces beyond the town site identified as locations for
      activity. Youth recommended the construction of a leisure centre, that healthier
      food be sold at the local convenience store, and the development of a community
      garden and berry farm. CONCLUSIONS: In the ecological framework, weight status is
      considered embedded within the larger ecology of individual lives because of
      interrelationships between an individual's personal dimensions and other
      components of an individual's external environment. Asset mapping with children
      and youth in Alexander First Nation helped to achieve an understanding of the
      community factors that shaped their health behaviors. Asset mapping not only
      produced a list of places and spaces where they played, met, and ate, but also
      showed where they most preferred to be. Further, the exercise enabled children to
      express how assets could be improved, and the assets they would like in their
      community, to promote healthy behaviors. The findings enabled adults to
      contextualize other community data collected about children (ie obesity
      prevalence, physical activity levels), to better understand how the presence and
      the condition of places and spaces in the community shaped the physical activity
      and eating behaviors of children and youth, and how local resources could be
      modified to be more health promoting.

PMID- 23534834
TI  - Association genetics of oleoresin flow in loblolly pine: discovering genes and
      predicting phenotype for improved resistance to bark beetles and bioenergy
      potential.
AB  - Rapidly enhancing oleoresin production in conifer stems through genomic selection
      and genetic engineering may increase resistance to bark beetles and terpenoid
      yield for liquid biofuels. We integrated association genetic and genomic
      prediction analyses of oleoresin flow (g 24 h(-1)) using 4854 single nucleotide
      polymorphisms (SNPs) in expressed genes within a pedigreed population of loblolly
      pine (Pinus taeda) that was clonally replicated at three sites in the
      southeastern United States. Additive genetic variation in oleoresin flow (h(2) ~
      0.12-0.30) was strongly correlated between years in which precipitation varied
      (r(a) ~ 0.95), while the genetic correlation between sites declined from 0.8 to
      0.37 with increasing differences in soil and climate among sites. A total of 231
      SNPs were significantly associated with oleoresin flow, of which 81% were
      specific to individual sites. SNPs in sequences similar to ethylene signaling
      proteins, ABC transporters, and diterpenoid hydroxylases were associated with
      oleoresin flow across sites. Despite this complex genetic architecture, we
      developed a genomic prediction model to accelerate breeding for enhanced
      oleoresin flow that is robust to environmental variation. Results imply that
      breeding could increase oleoresin flow 1.5- to 2.4-fold in one generation.

PMID- 23534836
TI  - Phosphorus as a simultaneous electron-pair acceptor in intermolecular P...N
      pnicogen bonds and electron-pair donor to Lewis acids.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been performed to investigate the
      structures and energies of binary complexes LA:PH2F and LA:PH3 and of ternary
      complexes LA:H2FP:NFH2 and LA:H3P:NH3 in which the pnicogen-bonded P atom also
      acts as an electron-pair donor to a Lewis acid (LA), for LA = BH3, NCH, ClH, FH,
      FCl, and HLi. Hydrogen bonds, halogen bonds, and dative covalent bonds are found
      at P in some cases, depending on the nature of the Lewis acid. HLi forms a
      lithium bond with P only in the binary complex HLi:PH3. The binding energies of
      ternary complexes exhibit a classical synergistic effect, although the computed
      cooperativity may be overestimated due to neglect of the interaction of the Lewis
      acid with NH2F or NH3 in some cases. The hydrogen-bonding Lewis acids appear to
      have little effect on the strength of the P...N bond, while the remaining Lewis
      acids strengthen the pnicogen bond. (31)P absolute chemical shieldings increase
      in LA:H2FP:NFH2 complexes relative to the corresponding LA:PH2F complexes as the
      positive charge on P decreases, while chemical shieldings decrease in LA:H3P:NH3
      relative to the corresponding LA:PH3 complexes as the positive charge increases.
      Absolute values of (1p)J(P-N) spin-spin coupling constants in complexes
      LA:H2FP:NFH2 decrease as the P-N distance decreases. It appears that this
      behavior is associated with the presence of a second intermolecular interaction,
      whether electron-donation by P or hydrogen bond formation at P-F.

PMID- 23534837
TI  - High blood manganese in iron-deficient children in Karachi.
AB  - OBJECTIVE: Dietary Fe deficiency has a high incidence in Pakistani children and
      may be associated with increased gastrointestinal absorption of trace metals such
      as Mn. Therefore, children residing in heavily polluted cities like Karachi may
      be prone to Mn toxicity. The present study investigated blood Mn concentrations
      in Karachi children of different Fe statuses. DESIGN: A prospective observational
      study was conducted where children were classified into different categories of
      Fe status - normal Fe, borderline Fe deficiency, Fe deficiency and Fe-deficiency
      anaemia - using WHO criteria supported by measurements of soluble transferrin
      receptors. Blood Mn was determined for children in each category using graphite
      atomic absorption spectroscopy. SETTING: Three hospital outpatient departments in
      Karachi, Pakistan. SUBJECTS: A total of 269 children (156 males, 113 females)
      aged 6-60 months from low-income families of Karachi. RESULTS: Blood Mn
      concentrations were significantly higher in children with Fe-deficiency anaemia
      and Fe deficiency compared with those of normal Fe status (both P,0?01). Blood
      concentrations of soluble transferrin receptors were higher in children with Fe
      deficiency anaemia compared with those of borderline or normal Fe status (both
      P,0?05). CONCLUSIONS: These findings report for the first time high blood Mn
      concentrations in Fe-deficient children of this age group. There is therefore an
      urgent need to identify and remove environmental exposure to Mn in combination
      with health strategies aimed at eradicating childhood Fe deficiency.

PMID- 23534838
TI  - Increased expression of toll-like receptor 4 on neurons after surgery in aged
      rats.

PMID- 23534839
TI  - How early do children understand gesture-speech combinations with iconic
      gestures?
AB  - Children understand gesture+speech combinations in which a deictic gesture adds
      new information to the accompanying speech by age 1;6 (Morford & Goldin-Meadow,
      1992; 'push'+point at ball). This study explores how early children understand
      gesture+speech combinations in which an iconic gesture conveys additional
      information not found in the accompanying speech (e.g., 'read'+BOOK gesture). Our
      analysis of two- to four-year-old children's responses in a gesture+speech
      comprehension task showed that children grasp the meaning of iconic co-speech
      gestures by age three and continue to improve their understanding with age.
      Overall, our study highlights the important role gesture plays in language
      comprehension as children learn to unpack increasingly complex communications
      addressed to them at the early ages.

PMID- 23534840
TI  - Children are not large mice.

PMID- 23534841
TI  - Abstracts of the Hong Kong Urological Association Annual Scientific Meeting.
      November 11, 2012. Hong Kong.

PMID- 23534843
TI  - A conductivity study of unsymmetrical 2:1 type "complex ion" electrolyte: cadmium
      chloride in dilute aqueous solutions.
AB  - Systematic and precise measurements of electrical conductivities of aqueous
      solutions of cadmium chloride were performed in the 2 * 10(-5)-1 * 10(-2) mol.dm(
      3) concentration range, from 278.15 to 313.15 K. Determined conductances were
      interpreted in terms of molecular model which includes a mixture of two 1:1 and
      2:1 electrolytes. The molar limiting conductances of lambda(0)(CdCl(+), T) and
      lambda(0)(1/2Cd(2+), T), the equilibrium constants of CdCl(+) formation K(T) and
      the corresponding standard thermodynamic functions were evaluated using the Quint
      Viallard conductivity equations, the Debye-Huckel equations for activity
      coefficients and the mass-action equation. An excellent agreement between
      calculated and experimental conductivities was reached.

PMID- 23534842
TI  - Adaptive behavior and later school achievement in children with early-onset
      epilepsy.
AB  - AIM: To determine whether early measures of adaptive behavior are predictive of
      later school difficulties and achievement in otherwise neurotypical (unimpaired)
      children with onset of epilepsy during the preschool years. METHOD: In a
      prospective cohort study, parents completed the Vineland Adaptive Behavior Scales
      (VABS) for children who were aged 5 years or less at epilepsy diagnosis. Eight to
      9 years later, the children were assessed using the Wechsler Intelligence Scales
      for Children (WISC), the Wide Range Achievement Test (WRAT), and the Child
      Behavior Checklist (CBCL). Associations of VABS scores with later WRAT and CBCL
      scores were tested. RESULTS: A total of 108 neurotypical children (64 males, 44
      females; mean age at testing 11 y 11 mo, SD 2 y) were studied. After adjustment
      for IQ and other factors, there was an increase of 0.15 points (95% confidence
      interval [CI] 0.03-0.27 points; p=0.03) and 0.14 points (95% CI 0.0-0.28 points;
      p=0.05) in WRAT reading and spelling scores for each 1-point increment in the
      VABS communication score. Corresponding numbers for the VABS socialization score
      were 0.20 (95% CI 0.08-0.32; p=0.005) and 0.17 (95% CI 0.05-0.29; p=0.005).
      CONCLUSION: In neurotypical preschool children with epilepsy, early social and
      communication scores predict later school performance. These findings raise
      questions about opportunities for early identification and intervention for
      children at greatest risk.

PMID- 23534844
TI  - The benefits of exercise for patients with haemophilia and recommendations for
      safe and effective physical activity.
AB  - Most health care professionals involved in the management of people with
      haemophilia (PWH) believe that exercise is beneficial and its practice is widely
      encouraged. This article aims to demonstrate that appropriate exercise (adapted
      to the special needs of the individual PWH) may be beneficial for all PWH through
      improved physical, psychosocial and medical status. Based on evidence gathered
      from the literature, many PWH, particularly those using long-term prophylaxis or
      exhibiting a mild/moderate bleeding phenotype, are as active as their healthy
      peers. PWH experience the same benefits of exercise as the general population,
      being physically healthier than if sedentary and enjoying a higher quality of
      life (QoL) through social inclusion and higher self-esteem. PWH can also gain
      physically from increased muscle strength, joint health, balance and flexibility
      achieved through physiotherapy, physical activity, exercise and sport.
      Conversely, very little data exist on activity levels of PWH in countries with
      limited resources. However, regarding specific exercise recommendations in PWH,
      there is a lack of randomized clinical trials, and consequently formal, evidence
      based guidelines have not been produced. Based on published evidence from this
      review of the literature, together with the clinical experience of the authors, a
      series of recommendations for the safe participation of PWH in regular physical
      activities, exercises and sport are now proposed. In summary, we believe that
      appropriately modified programmes can potentially allow all PWH to experience the
      physical and psychosocial benefits of being physically active which may
      ultimately lead to an improved QoL.

PMID- 23534845
TI  - A psychometric investigation of the hypersexual disorder screening inventory
      among highly sexually active gay and bisexual men: an item response theory
      analysis.
AB  - INTRODUCTION: The Hypersexual Disorder Screening Inventory (HDSI) was designed as
      an instrument for the screening of hypersexuality by the American Psychiatric
      Association's taskforce for the fifth edition of the Diagnostic and Statistical
      Manual of Mental Disorders. AIM: Our study sought to conduct a psychometric
      analysis of the HDSI, including an investigation of its underlying structure and
      reliability utilizing item response theory (IRT) modeling, and an examination of
      its polythetic scoring criteria in comparison to a standard dimensionally based
      cutoff score. METHODS: We examined a diverse group of 202 highly sexually active
      gay and bisexual men in New York City. We conducted psychometric analyses of the
      HDSI, including both confirmatory factor analysis of its structure and IRT
      analysis of the item and scale reliabilities. MAIN OUTCOME MEASURES: We utilized
      the HDSI. RESULTS: The HDSI adequately fit a single-factor solution, although
      there was evidence that two of the items may measure a second factor that taps
      into sex as a form of coping. The scale showed evidence of strong reliability
      across much of the continuum of hypersexuality, and results suggested that, in
      addition to the proposed polythetic scoring criteria, a cutoff score of 20 on the
      severity index might be used for preliminary classification of HD. CONCLUSION:
      The HDSI was found to be highly reliable, and results suggested that a
      unidimensional, quantitative conception of hypersexuality with a clinically
      relevant cutoff score may be more appropriate than a qualitative syndrome
      comprised of multiple distinct clusters of problems. However, we also found
      preliminary evidence that three clusters of symptoms may constitute an HD
      syndrome as opposed to the two clusters initially proposed. Future research is
      needed to determine which of these issues are characteristic of the
      hypersexuality and HD constructs themselves and which are more likely to be
      methodological artifacts of the HDSI.

PMID- 23534846
TI  - The delivery of smoking cessation interventions to primary care patients with
      mental health problems.
AB  - AIMS: To quantify the extent to which smokers with indicators of poor mental
      health receive smoking cessation support in primary care consultations compared
      with those without. DESIGN: Cross-sectional study within a database of electronic
      primary care medical records. SETTING: A total of 495 general practices in the
      United Kingdom contributing data to The Health Improvement Network (THIN)
      database. PARTICIPANTS: A total of 2 493 085 patients aged 16+ registered with a
      THIN practice for the year from 1 July 2009 to 30 June 2010. MEASUREMENTS: The
      proportion of patients with a diagnostic Read code or British National Formulary
      (BNF) drug code indicating a mental health diagnosis or psychoactive medication
      prescription, respectively, who smoke and who have cessation advice or a smoking
      cessation medication prescription recorded during consultations within the 1-year
      study period. FINDINGS: Of 32 154 smokers, 50.6% [95% confidence interval (CI):
      50.0-51.2] with a mental health diagnosis and 49.3% (95% CI: 49.0-49.7) of 96 285
      smokers prescribed a psychoactive medication had a record of cessation advice,
      higher than the prevalence of advice recording in smokers without these
      indicators (33.4%, 95% CI: 33.3-33.6). Similarly, smoking cessation medication
      prescribing was higher: 11.2% (95% CI: 10.8-11.6) of smokers with a mental health
      diagnosis and 11.0% (95% CI: 10.8-11.2) of smokers prescribed psychoactive
      medication received a prescription, compared with 6.73% of smokers without these
      indicators (95% CI: 6.65-6.81). Smoking cessation support was offered in a lower
      proportion of consultations for smokers with indicators of poor mental health
      than for those without. Advice was recorded in 7.9% of consultations with smokers
      with a mental health diagnosis, 8.2% of consultations with smokers prescribed
      psychoactive medication and 12.3% of consultations with smokers without these
      indicators; comparable figures for prescribing of cessation medication were 2.9%,
      3.2% and 4.4%, respectively. CONCLUSIONS: Approximately half of smokers with
      indicators of poor mental health receive advice to quit during primary care
      consultations in the United Kingdom, and one in 10 receive a cessation
      medication. Interventions are lower per consultation for smokers with mental
      health indicators compared with smokers without mental health indicators.

PMID- 23534847
TI  - Top-down interrogation of chemically modified oligonucleotides by negative
      electron transfer and collision induced dissociation.
AB  - Two sets of synthetic 21-23mer oligonucleotides with various types of 2'-position
      modifications have been studied with tandem mass spectrometry using ion trap
      collision-induced dissociation (IT-CID) and negative electron transfer (NET)-CID.
      A systematic study has been conducted to define the limitations of IT-CID in
      sequencing such 2'-chemically modified oligonucleotides. We found that IT-CID is
      sufficient in characterizing oligonucleotide sequences that do not contain DNA
      residues, where high sequence coverage can be achieved by performing IT-CID on
      multiple charge states. However, oligonucleotides containing DNA residues gave
      limited backbone fragmentation with IT-CID, largely due to dominant fragmentation
      at the DNA residue sites. To overcome this limitation, we employed the negative
      electron transfer to strip an electron from the multiply charged oligonucleotide
      anion. Then, the radical anion species formed in this reaction can fragment via
      an alternative radical-directed dissociation mechanism. Unlike IT-CID, NET-CID
      mainly generates a noncomplementary d/w ion series. Furthermore, we found that
      NET-CID did not show preferential dissociations at the DNA residue sites and thus
      generated higher sequence coverage for the studied oligonucleotide. Information
      from NET-CID of different charge states is not fully redundant such that the
      examination of multiple charge states can lead to more extensive sequence
      confirmation. This work demonstrates that the NET-CID is a valuable tool to
      provide high sequence coverage for chemically modified oligonucleotides, and such
      detailed characterization can serve as an important assay to control the quality
      of therapeutic oligonucleotides that are produced under the good manufacture
      practice (GMP) regulations. 

PMID- 23534848
TI  - Loss of siloxane monolayers from GaN surfaces in water.
AB  - Gallium nitride, with a thin passivating layer of Ga2O3, has been functionalized
      with octadecyltrichlorosilane (OTS) and aminopropyltriethoxysilane (APTES) self
      assembled monolayers (SAMs). Water contact angles, atomic force microscopy, and X
      ray photoelectron spectroscopy were used for characterization of the bare and
      functionalized surfaces. The SAMs are stable in acetonitrile, but both the
      hydrophobic OTS SAM and the hydrophilic APTES SAM completely desorb after 1-24 h
      of immersion in water and common buffers. The concentration of gallium in
      solution after a clean GaN chip is immersed in water is consistent with
      dissolution of roughly one monolayer of interfacial gallium oxide. Dissolution of
      this oxide layer could account for the loss of SAMs from GaN surfaces.

PMID- 23534849
TI  - Surface patterning of mesoporous niobium oxide films for solar energy conversion.
AB  - An array of periodic surface features were patterned on mesoporous niobium oxide
      films by a soft-lithographic technique with the goal of constructing a photonic
      crystal (PC) structure on the back side of the oxide. The oxide films, fabricated
      by mixing sol-gel derived niobium oxide nanoparticles and hydroxypropyl
      cellulose, were employed as photoelectrodes in dye-sensitized solar cells
      (DSSCs), and their performance evaluated against their flat counterparts. The
      surface patterns were imprinted using a photocurable perfluoropolyether (PFPE)
      soft-replica of a silicon master with a two-dimensional array of cylindrical
      posts (200 nm (D) * 200 nm (H)) in hexagonal geometry. The PC on the niobium
      oxide surface caused large changes in optical measurements, particularly in the
      blue wavelengths. To evaluate the optical effect on solar energy conversion, the
      incident photon-to-current conversion efficiency (IPCE) was measured in the
      patterned devices and the control group. The IPCE of patterned niobium oxide
      anodes exhibited a relative enhancement in photocurrent generation over the
      wavelength range corresponding to the higher absorption in optical measurements.

PMID- 23534850
TI  - Sodium butyrate promotes generation of human induced pluripotent stem cells
      through induction of the miR302/367 cluster.
AB  - Small molecules (SM) can greatly enhance the efficiency of induced pluripotent
      stem (iPS) cell generation, but the mechanisms by which they act have not been
      fully explored. We show here that an SM cocktail (NaB, PD03259, and SB431542)
      significantly promotes iPS cell generation from human fibroblasts, and NaB is
      more potent than the other two common histone deacetylase inhibitors (valproic
      acid and Trichostatin A) in promoting cellular reprogramming. Our data indicate
      that the SM cocktail substantially upregulates the miR302/367 cluster expression
      by increasing the stability and transcriptional level of this microRNA (miRNA)
      cluster in a manner dependent on the four defined transcription factors (TFs).
      Among the four TFs, Oct4 in particular appears to be required for the induction
      of the miR302/367 cluster by the SM cocktail. We also found that NaB alone can
      enhance the TFs-dependent upregulation of the miR302/367 cluster. Using a
      promoter reporter assay, we show that the SM cocktail remarkably enhanced the
      transcriptional activity of the four TFs in the miR302/367 promoter. Notably,
      attenuation of miRNA302/367 using a miRZip impairs the ability of the SM cocktail
      in promoting reprogramming. Collectively, these findings suggest that the SM
      cocktail promotes reprogramming at least partly through the induction of the
      miR302/367 cluster expression. Further insights into this process may pave the
      way for the generation of iPS cells using only SM cocktails.

PMID- 23534851
TI  - Informal talk: shaping understandings of sexually transmitted infections (STIs)
      in rural Australia.
AB  - INTRODUCTION: Although there have been great strides in the prevention, care and
      treatment of sexually transmitted infections (STIs, including HIV) in Australia,
      the increasing trend towards higher rates of some STIs is of concern, especially
      reports of higher rates of chlamydia in inner regional areas. Reasons for these
      changes are unclear but suggest there is an inconsistent use of prevention
      measures and ambivalence towards acting responsibly around sexual behaviours.
      Understanding an individual's response to the circumstances or contexts in which
      knowledge about STIs are operationalised in rural communities becomes central to
      recognising how individuals experience health and illness, especially for
      developing interventions to prevent the transmission of STIs. The aim of this
      research is to understand how individuals in rural communities make sense of
      their experiences in relation to STIs and how rurality influences discussion
      about STIs and health-seeking behaviours. METHOD: In-depth interviews with 24
      participants, 18 females and 6 males, aged between 19 and 65 years provide the
      data for the study. Methodological principles of 'grounded theory' underpin the
      analysis. An eclectic approach to grounded theory was used in the current study
      that was derived from a number of authors. RESULTS: The findings revealed that a
      number of contexts shape the actions and reactions of rural individuals towards
      STIs. These include 'public and private world of individuals', 'forms of talking
      in rural communities' and 'managing information and use of health services'.
      Factors that shape social life in rural communities such as the social bonds that
      are present, the relationships developed, and the way in which people behave
      influence the public and private aspects of rural life. Different forms of talk
      were identified that indicate that sexual issues are discussed in a number of
      informal ways and encompass distinct experiences of conveying information with
      regard to sex and STIs. Managing information and use of health services occurs
      when individuals assess and identify the need to access services for STIs.
      CONCLUSIONS: The strength of this research lies in the identification of a number
      of contexts such as the private-public divide and types of talk where informal
      mechanisms encourage individuals to conform and comply with community rules and
      values. Using informal talk as a health promotion and or prevention strategy in
      rural locations can provide an alternative approach to potentially changing
      social norms. It would be possible to extend the idea of positive informal talk
      to include symbols and imagery that encourage individuals to seek treatment and
      provide a more positive view of 'reputation'. Engaging rural individuals in
      positive talk about sexual risk, access to treatment for STIs, and provision of
      accurate knowledge can help to build new 'social norms' that encourage new
      interpretations.

PMID- 23534853
TI  - A cross-cultural content-analytic comparison of the hookup culture in U.S. and
      Dutch teen girl magazines.
AB  - This quantitative content analysis investigated the hookup culture in U.S. and
      Dutch teen girl magazines. Using Hofstede's cultural dimension of
      masculinity/femininity, the hookup culture (i.e., the relational context of sex,
      emotional context of sex, specific sexual activities, and contraceptives) was
      examined in 2,496 stories from all 2006 through 2008 issues of the three most
      popular U.S. (i.e., Seventeen, CosmoGirl! U.S. edition, and Teen) and Dutch teen
      girl magazines (i.e., Fancy, CosmoGirl! Netherlands edition, and Girlz!).
      Regarding the relational context of sex, stories about casual sex occurred more
      often in U.S. magazines, and Dutch magazines focused more on committed sex. Dutch
      magazines also emphasized sex within the emotional context of love more often
      than did U.S. magazines. In terms of sexual activities, coital sex was mentioned
      more often in U.S. coverage, while petting was mentioned more frequently in Dutch
      coverage. Condoms were covered more positively in U.S. magazines than in Dutch
      magazines. Overall, the hookup culture seems to be more visible in U.S. magazines
      for the occurrence of casual sex and lack of love stories, whereas it does not
      emerge in Dutch magazines due to the presence of committed sex and love-related
      articles. 

PMID- 23534852
TI  - Natural experimentation is a challenging method for identifying headache
      triggers.
AB  - OBJECTIVE: In this study, we set out to determine whether individual headache
      sufferers can learn about the potency of their headache triggers (causes) using
      only natural experimentation. BACKGROUND: Headache patients naturally use the
      covariation of the presence-absence of triggers with headache attacks to assess
      the potency of triggers. The validity of this natural experimentation has never
      been investigated. A companion study has proposed 3 assumptions that are
      important for assigning causal status to triggers. This manuscript examines one
      of these assumptions, constancy in trigger presentation, using real-world
      conditions. METHODS: The similarity of day-to-day weather conditions over 4
      years, as well as the similarity of ovarian hormones and perceived stress over a
      median of 89 days in 9 regularly cycling headache sufferers, was examined using
      several available time series. An arbitrary threshold of 90% similarity using
      Gower's index identified similar days for comparison. RESULTS: The day-to-day
      variability in just these 3 headache triggers is substantial enough that finding
      2 naturally similar days for which to contrast the effect of a fourth trigger
      (eg, drinking wine vs not drinking wine) will only infrequently occur.
      Fluctuations in weather patterns resulted in a median of 2.3 days each year that
      were similar (range 0-27.4). Considering fluctuations in stress patterns and
      ovarian hormones, only 1.5 days/month (95% confidence interval 1.2-2.9) and 2.0
      days/month (95% confidence interval 1.9-2.2), respectively, met our threshold for
      similarity. CONCLUSION: Although assessing the personal causes of headache is an
      age-old endeavor, the great many candidate triggers exhibit variability that may
      prevent sound conclusions without assistance from formal experimentation or
      statistical balancing.

PMID- 23534854
TI  - An interprofessional process to improve early identification and treatment for
      sepsis.
AB  - The course of sepsis is rapid. Patient outcomes improve when sepsis is diagnosed
      and treated quickly. The clinical goals of the evidence-based bundled strategies
      from the International consortium Surviving Sepsis Campaign (SSC) include
      optimizing timeliness in the delivery of care and creating a continuum for sepsis
      management that runs from the emergency department (ED) to the acute and critical
      care settings. Successful implementation of processes that integrate sepsis
      bundles can improve patient mortality and hospital costs. Improving
      interprofessional education and collaboration are necessary to facilitate the
      effective use of bundled strategies. An intervention that included
      interprofessional education resulted in a statistically significant difference
      between the three phases studied. There was a statistically significant
      improvement between the phases for lactate completion X(2) = 16.908 (p < .01)
      after education. Frequency of blood cultures being obtained before antibiotic
      administration was nearing statistical significance (p < .054). There was an
      improvement in time to antibiotic administration between phase 2 (182.09 mean
      average minutes, SD = 234.06) and phase 3 (91.62 mean average minutes, SD =
      167.99).

PMID- 23534855
TI  - A role for polyglucans in a model sea urchin embryo cellular interaction.
AB  - The enzymatic activities of commercially prepared glycosidases were verified by
      direct chemical assays using defined substrates and fixed and live sea urchin
      (Lytechinus pictus) embryos to determine if a model cellular interaction of
      interest to developmental biologists for over a century (interaction of
      archenteron tip and roof of the blastocoel) was mediated by glycans. Glycosidases
      (active and denatured) were incubated with microdissected archenterons and
      blastocoel roofs in a direct assay to learn if their enzymatic activities could
      prevent the normal adhesive interaction. Of the five glycosidases tested only
      beta-amylase (an exoglycosidase) immediately inhibited the interaction at
      relatively low unit activity. alpha-Amylase (an endoglycosidase) had no
      measurable effect, while other glycosidases (alpha-glucosidase, beta-glucosidase,
      beta-galactosidase) only substantially inhibited adhesion after a 12-h
      incubation. We demonstrated that the five glycosidases were active (not
      inhibited) in the presence of embryo materials, and that cleaved sugars could be
      detected directly after incubation of some enzymes with the embryos. The
      biochemical purity of the enzymes was examined using gel electrophoresis under
      denaturing conditions, and the absence of contaminating proteases was confirmed
      using AzocollTM substrate. As we cannot entirely rule out the presence of minor
      contaminating enzymatic activities, only inhibitions of adhesion after very short
      incubations with enzyme were considered significant and biologically relevant.
      Although glycans in indirect experiments have been implicated in mediating the
      interaction of the tip of the archenteron and roof of the blastocoel, to our
      knowledge, this is the first study that directly implicates polyglucans with
      terminal 1,4-linked glucose residues in this adhesive event.

PMID- 23534856
TI  - Similarity in joint function limitation in Type 3 von Willebrand's disease and
      moderate haemophilia A.
AB  - Type 3 von Willebrand's disease (VWD) is a rare bleeding diathesis with complete
      or near complete deficiency of von Willebrand factor (VWF) and low factor VIII
      (FVIII) levels. In contrast, only FVIII is decreased in haemophilia A (HA). Both
      disorders are complicated by arthropathy. The purpose of this study was to
      further clarify the roles of FVIII and VWF: Antigen (VWF:Ag) in joint range of
      motion (ROM) loss over time. We compared joint ROM loss and other bleeding
      manifestations in 100 Type 3 VWD subjects (FVIII<5%) and 1814 moderate HA
      subjects (FVIII 1-5%) within the U.S. Universal Data Collection (UDC) database.
      High rates of bleeding were reported at baseline. During follow-up, moderate HA
      patients reported a joint (46% vs. 34%, P < 0.0001) or muscle bleed (27% vs. 16%,
      P < 0.0001) in a higher proportion of visits than VWD patients. Other bleeds,
      including mucosal, were reported in a greater proportion of visits among patients
      with Type 3 VWD than among those with HA (49% vs. 32%, P < 0.0001). Multivariate
      analysis revealed no difference in joint ROM loss over time in the Type 3 VWD vs.
      moderate HA populations. A higher FVIII level was protective in both VWD and HA
      (P < 0.001). Our findings support the hypothesis of primacy of the FVIII level in
      determining risk of joint haemorrhage, and may help target therapy in Type 3 VWD
      and moderate HA to prevent joint disability.

PMID- 23534857
TI  - Skin sensitization of epoxyaldehydes: importance of conjugation.
AB  - Structure-activity relationship (SAR) models are important tools for predicting
      the skin sensitization potential of new compounds without animal testing. In
      compounds possessing a structural alert (aldehyde) and an activation alert
      (double bond), it is important to consider bioactivation/autoxidation (e.g.,
      epoxidation). In the present study, we have explored a series of aldehydes with
      regard to contact allergy. The chemical reactivity of these 6 aldehydes toward a
      model hexapeptide was investigated, and their skin sensitization potencies were
      evaluated using the local lymph node assay (LLNA). Overall, we observed a similar
      trend for the in vitro reactivity and the in vivo sensitization potency for the
      structural analogues in this study. The highly reactive conjugated aldehydes
      (alpha,beta-unsaturated aldehydes and 2,3-epoxyaldehydes) are sensitizing
      moieties, while nonconjugated aldehydes and nonterminal aliphatic epoxides show
      low reactivity and low sensitization potency. Our data show the importance of not
      only double bond conjugation to aldehyde but also epoxide-aldehyde conjugation.
      The observations indicate that the formation of nonconjugated epoxides by
      bioactivation or autoxidation is not sufficient to significantly increase the
      sensitization potency of weakly sensitizing parent compounds.

PMID- 23534858
TI  - Melittin creates transient pores in a lipid bilayer: results from computer
      simulations.
AB  - To study the interaction between melittin peptides and lipid bilayer, we
      performed coarse-grained simulations on systems containing melittin interacting
      with a bilayer containing zwitterionic dipalmitoylphosphatidylcholine (DPPC) and
      anionic palmitoyloleoylphosphatidylglycerol (POPG) phospholipids in a 7:3 ratio.
      Eight different systems were considered: four at low and four at high peptide to
      lipid (P/L) ratios. In case of low P/L ratio we did not observe any pore creation
      in the bilayer. In two out of four of the simulations with the high P/L ratio,
      appearance of transient pores in the bilayer was observed. These pores were
      created due to an assembly of 3-5 melittin peptides. Not all of the peptides in
      the pores were in a transmembrane conformation; many of them had their termini
      residues anchored to the same leaflet, and these peptides assumed bent, U-shaped,
      conformations. We propose that when an assembly of melittin peptides creates
      pores, such an assembly acts as a "wedge" that splits the bilayer. To get a more
      detailed description of melittin on the bilayer surface and in transient pores,
      we performed coarse-grained to united-atom scale transformations and after that
      performed 50 ns molecular dynamics simulations using the united atom description
      of the systems. While these simulations did not show much of the change in the
      pore structure during the 50 ns time interval, they clearly showed the presence
      of water in the transient pores. The appearance of transient pores together with
      the translocation of peptides across the membranes is consistent with the
      mechanism proposed to explain graded dye leakage from large vesicles in the
      presence of melittin.

PMID- 23534859
TI  - Health disparities among highly vulnerable populations in the United States: a
      call to action for medical and oral health care.
AB  - Healthcare in the United States (US) is burdened with enormous healthcare
      disparities associated with a variety of factors including insurance status,
      income, and race. Highly vulnerable populations, classified as those with complex
      medical problems and/or social needs, are one of the fastest growing segments
      within the US. Over a decade ago, the US Surgeon General publically challenged
      the nation to realize the importance of oral health and its relationship to
      general health and well-being, yet oral health disparities continue to plague the
      US healthcare system. Interprofessional education and teamwork has been
      demonstrated to improve patient outcomes and provide benefits to participating
      health professionals. We propose the implementation of interprofessional
      education and teamwork as a solution to meet the increasing oral and systemic
      healthcare demands of highly vulnerable US populations.

PMID- 23534860
TI  - Assessment of maxillary and infraorbital nerve blockade for rhinoscopy in
      sevoflurane anesthetized dogs.
AB  - OBJECTIVE: To investigate the efficacy of maxillary and infraorbital nerve blocks
      for prevention of cardiovascular and qualitative responses to rhinoscopy, as well
      as response to skin clamping after assigned nerve block placement. STUDY DESIGN:
      Randomized, blinded, placebo-controlled cross-over experimental study. ANIMALS:
      Eight random-source mixed breed dogs > 1 year old and weighing between 13 and 22
      kg. METHODS: Within three anesthetic episodes, separated by at least 3 days, dogs
      were assigned to receive either 1 mL lidocaine 2% maxillary nerve block (ML); 0.5
      mL lidocaine 2% infraorbital nerve block (IOL); or equal amounts of saline for
      maxillary or infraorbital nerve block combined as control treatment (S).
      Monitoring included temperature, respiratory rate, end-tidal CO2 , ECG, heart
      rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP, MAP).
      Posterior (pR) and anterior rhinoscopies (aR) were performed and scored.
      Differences from baseline for outcome parameters HR, SAP, DAP, MAP were analyzed
      using repeated-measures anova, and results reported as mean +/- SD. Binary scores
      for rhinoscopy were analyzed using logistic regression, and odds ratio was
      reported. RESULTS: Changes from baseline for HR and SAP were significant for all
      treatments, besides ML for pR. Difference in changes from baseline among
      treatments was statistically significant for HR during pR with ML < S, and for
      SAP, DAP and MAP in right and left aR with ML < S and IOL > ML, except for DAP in
      left aR with only IOL > ML. Analysis of the binary score showed that the
      probability of a response for S and IOL treatments was nearly triple that of the
      ML treatment. None of the dogs, regardless of the treatments applied, responded
      to skin clamping. CONCLUSION AND CLINICAL RELEVANCE: Cardiovascular parameters do
      not seem to reflect the occurrence of adverse reactions during rhinoscopy. The
      maxillary nerve block is superior to the infraorbital nerve block, as applied in
      this study, in preventing adverse reactions during posterior rhinoscopy.

PMID- 23534861
TI  - Resistance and barriers to local estrogen therapy in women with atrophic
      vaginitis.
AB  - INTRODUCTION: Vaginal atrophy results from a decrease in circulating estrogen and
      is experienced by approximately 50% of postmenopausal women. Its symptoms affect
      multiple dimensions of genitopelvic health, sexuality, and overall quality of
      life. Nonhormonal over-the-counter treatments may provide temporary symptom
      relief, but the condition is progressive, and hormonal treatment may be
      warranted. AIM: The study aims to review the literature and discuss the impact of
      atrophic vaginitis and various treatment options, including the resistance and
      barriers to the use of local estrogen therapy for atrophic vaginitis. This
      article also aims to provide a greater awareness of the condition and the
      difficulties in communicating effectively with patients, and to provide
      strategies to help healthcare professionals acquire effective communication
      skills to initiate a candid dialogue with patients who may be suffering in
      silence and may benefit from therapy. METHODS: This review was based on peer
      reviewed publications on the topic of atrophic vaginitis and local estrogen
      therapy identified from key word searches of PubMed, in addition to landmark
      studies/surveys and treatment guidelines/recommendations on menopause available
      in the literature and on the Internet. MAIN OUTCOME MEASURES: The main outcomes
      are the impact of atrophic vaginitis and the various treatment options, including
      the resistance and barriers to the use of local estrogen therapy. RESULTS:
      Minimally absorbed local vaginal estrogen therapy enables administration of
      estrogen doses much lower than systemic doses used for vasomotor symptoms. Local
      therapy is also the first-line pharmacologic treatment recommended by the North
      American Menopause and International Menopause Societies. Despite treatment
      options, the sensitive nature of the condition and embarrassment may prohibit or
      limit many women from openly discussing symptoms with healthcare professionals.
      Many are hesitant to initiate hormonal treatment because of safety concerns.
      CONCLUSIONS: Healthcare professionals should initiate and encourage frank and
      candid conversation about vaginal atrophy at annual visits and provide follow-up
      and treatment as needed.

PMID- 23534864
TI  - Electrochemical properties of ZrO2-doped V2O5 amorphous powders with spherical
      shape and fine size.
AB  - Amorphous V2O5 powders with zirconia (ZrO2) dopant are prepared by one-pot spray
      pyrolysis at temperatures above the melting temperature of V2O5. The powders with
      7 wt % ZrO2 are completely spherical and dense with a clean surface, on which
      crystals of pure V2O5 powders are scarcely observed. The V2O5 powders with 7 wt %
      ZrO2 have uniformly distributed V and Zr components. The uniformly distributed Zr
      component disturbs the crystallization of V2O5 during the quenching of the melted
      powders. These powders also give smooth initial discharge curves with a single
      slope, which is typical to amorphous materials. The discharge capacities of the
      V2O5 powders with 7 wt % ZrO2 are 309, 269, and 222 mA h g(-1) after the first,
      second, and 50th cycles, respectively, even at a high current density of 294 mA
      g(-1). The capacity retention measured after the first cycle is 83% after 50
      cycles.

PMID- 23534863
TI  - Fungal community analysis by high-throughput sequencing of amplified markers--a
      user's guide.
AB  - Novel high-throughput sequencing methods outperform earlier approaches in terms
      of resolution and magnitude. They enable identification and relative
      quantification of community members and offer new insights into fungal community
      ecology. These methods are currently taking over as the primary tool to assess
      fungal communities of plant-associated endophytes, pathogens, and mycorrhizal
      symbionts, as well as free-living saprotrophs. Taking advantage of the collective
      experience of six research groups, we here review the different stages involved
      in fungal community analysis, from field sampling via laboratory procedures to
      bioinformatics and data interpretation. We discuss potential pitfalls,
      alternatives, and solutions. Highlighted topics are challenges involved in:
      obtaining representative DNA/RNA samples and replicates that encompass the
      targeted variation in community composition, selection of marker regions and
      primers, options for amplification and multiplexing, handling of sequencing
      errors, and taxonomic identification. Without awareness of methodological biases,
      limitations of markers, and bioinformatics challenges, large-scale sequencing
      projects risk yielding artificial results and misleading conclusions.

PMID- 23534865
TI  - The folate status of reproductive-aged women in a randomised trial of a folate
      fortified oral contraceptive: dietary and blood assessments.
AB  - OBJECTIVE: To assess the folate status of US women in a study of a folate
      fortified oral contraceptive (OC) using the Short Folate Food Frequency
      Questionnaire and plasma and red blood cell (RBC) folate samples. DESIGN: Sub
      analysis from a multi-centre, randomised, double-blind, controlled contraceptive
      trial with assessments at baseline and 6 months. We calculated dietary folate
      equivalents (DFE) consumed and the proportion of participants meeting folate
      adequacy benchmarks. SETTING: Eight centres in the USA. SUBJECTS: Healthy women
      aged 18-40 years requesting contraception with no contraindications for OC use.
      RESULTS: Overall, 385 participants were randomised to either a novel folate
      fortified OC or a marketed OC. The 262 (68 %) participants compliant with the
      protocol were included in the analysis set. Baseline daily DFE consumption was
      529.8 (sd 342.1) MUg and similar in both groups. At follow-up, the fortified OC
      group had higher intake than the conventional OC group (1225.9 (sd 346.2) MUg
      compared with 500.6 (sd 361.2) MUg). Mean plasma folate level increased from 44.5
      (sd 17.2) to 55.8 (sd 21.1) nmol/l. Mean RBC folate level increased from 996.7
      (sd 369.8) to 1311.9 (sd 436.0) nmol/l. The proportion meeting selected folate
      adequacy benchmarks increased in the fortified OC group (P < 0.001). CONCLUSIONS:
      Lack of adequate folate intake in reproductive-aged women from dietary sources or
      supplements alone suggests the need for novel approaches. Use of folate-fortified
      OC ensures adequate folate levels and meeting of folate benchmarks.

PMID- 23534866
TI  - Estimating the mechanical properties of retinal tissue using contact angle
      measurements of a spreading droplet.
AB  - When a drop of liquid is placed on the surface of a soft material, the surface
      deformation and the rate of spreading of the triple contact point is dependent on
      the mechanical properties of the substrate. This study seeks to use drop
      spreading behavior to infer the mechanical properties of soft biological
      materials. As an illustration of the value of this technique we have compared the
      spreading behavior of a liquid droplet on two viscoelastic, soft materials,
      namely, an elastomer and a low concentration agar gel. The ratio of the
      mechanical properties of these soft materials obtained in this way is confirmed
      by atomic force microscopy (AFM) nanoindentation. By comparing the spreading
      behavior of a liquid on the retina with that of the same liquid on each of two
      viscoelastic materials, we can then estimate the elastic moduli of the retina: an
      estimate that is extremely difficult to carry out using AFM.

PMID- 23534867
TI  - Randomized approximation methods for the efficient compression and analysis of
      hyperspectral data.
AB  - Hyperspectral imaging techniques such as matrix-assisted laser desorption
      ionization (MALDI) mass spectrometry imaging produce large, information-rich
      datasets that are frequently too large to be analyzed as a whole. In addition,
      the "curse of dimensionality" adds fundamental limits to what can be done with
      such data, regardless of the resources available. We propose and evaluate random
      matrix-based methods for the analysis of such data, in this case, a MALDI mass
      spectrometry image from a section of rat brain. By constructing a randomized
      orthornormal basis for the data, we are able to achieve reductions in
      dimensionality and data size of over 100 times. Furthermore, this compression is
      reversible to within noise limits. This allows more-conventional multivariate
      analysis techniques such as principal component analysis (PCA) and clustering
      methods to be directly applied to the compressed data such that the results can
      easily be back-projected and interpreted in the original measurement space. PCA
      on the compressed data is shown to be nearly identical to the same analysis on
      the original data but the run time was reduced from over an hour to 8 seconds. We
      also demonstrate the generality of the method to other data sets, namely, a
      hyperspectral optical image of leaves, and a Raman spectroscopy image of an
      artificial ligament. In order to allow for the full evaluation of these methods
      on a wide range of data, we have made all software and sample data freely
      available.

PMID- 23534868
TI  - CFH (rs1410996), HTRA1 (rs112000638) and ARMS2 (rs10490923) gene polymorphisms
      are associated with AMD risk in Spanish patients.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the main cause of legal
      blindness in the western adult population. We investigated the association
      between SNPs located in CFH, ARMS2 and HTRA1 and AMD in Spanish patients.
      PATIENTS AND METHODS: We obtained peripheral blood samples from 121 patients with
      a diagnosis of AMD (84 exudative and 37 atrophic) at the Department of
      Ophthalmology of the University Hospital of Salamanca. We took 91 subjects as a
      control group. We studied a single nucleotide polymorphism (SNP) in each patient
      for each of the genes associated with high susceptibility to developing AMD using
      Real-time PCR with TaqMan probes for CFH and ARMS2 polymorphisms and PCR-RFLP for
      HTRA1 polymorphism. RESULTS: We observed a statistically significant difference
      between patients and controls in the distribution of CFH rs1410996 genotypes,
      patients homozygous for the C-allele have twice the risk of developing the
      disease (p = 0.010; OR = 2,176 (1.194-3.964)). The analysis of ARMS2 rs10490923
      polymorphism also showed differences in allelic distribution between the case and
      control groups (p < 0.001). Carriers of the T-allele appear more frequently in
      the group of patients (p < 0.001; O  = 3.340 (1.848-6.060)). Our results also
      confirm significant differences in the distribution of HTRA1 rs112000638
      polymorphism with an increased representation of the G-allele in the patient's
      group (p < 0.001; OR = 6.254(3.463-12.280)). Our study also indicates that TTGG
      ARMS2/HTRA1 (rs10490923/rs112000638) haplotype increases the risk of developing
      AMD by 9 times. CONCLUSIONS: Our results show that genotypes of ARMS2
      (rs10490923), HTRA1 (rs112000638) and CFH (rs1410996) polymorphisms are related
      to an increased risk of suffering AMD in Spanish patients.

PMID- 23534870
TI  - Increasing sensitivity in determining chemical shifts in one dimensional
      Lorentzian NMR spectra.
AB  - An algorithm is presented for one-dimensional NMR systems that employs nonlinear,
      non-Fourier methods to convert noisy time-dependent free induction decay (FID)
      data to a denoised frequency spectrum that gives reliable chemical shifts and
      coupling constants when the spectrum is Lorentzian. It is formulated in a way
      that increases frequency sensitivity and resolution and, for nuclei of low
      natural abundance, potentially avoids enrichment totally or in part. The
      algorithm should also be of use in analytical chemistry where enrichment is not
      possible. In effect, the useful limit of detection is significantly lowered. The
      algorithm uses new "phasing" and "feature stability upon accumulation" methods to
      reliably separate signal from noise at low signal-to-noise ratios where the
      Fourier spectrum requires many more transients to be definitive as to what is
      signal and what is noise. The long-standing problem of "false features" that
      plagued many prior attempts to employ nonlinear methods is thereby resolved for
      Lorentzian spectra. Examples are reported, and the limitations of the algorithm
      are discussed.

PMID- 23534869
TI  - Perceived stress and biological risk: is the link stronger in Russians than in
      Taiwanese and Americans?
AB  - Allostatic load theory implies a relationship between exposure to psychological
      stress and multi-system physiological dysregulation. We used data from population
      based samples of men and women in Russia (Moscow; n = 1800; age, mean 68.6
      years), Taiwan (n = 1036; 65.6 years) and the United States (US; n = 1054; 58.0
      years) -- which are likely to vary widely with respect to levels of stress
      exposure and biological markers -- to determine the magnitude of the association
      between perceived stress and physiological dysregulation. The measure of overall
      dysregulation was based on 15 markers including standard cardiovascular/metabolic
      risk factors as well as markers of inflammation and neuroendocrine activity.
      Subjective psychological stress was measured by the perceived stress scale. Only
      the Moscow sample demonstrated a positive association with overall dysregulation
      in both sexes. In the US, we found an association among women but not men. Among
      the Taiwanese, who report the lowest perceived stress, there was no association
      in women but an unexpected inverse relationship in men. The effects also varied
      across system-level subscores: the association with perceived stress was most
      consistent for standard cardiovascular/metabolic factors. Perceived stress was
      associated with inflammation and neuroendocrine activity in some samples.
      Although the evidence that perceived stress is the primary source of
      physiological dysregulation is generally modest, it was stronger in Russia where
      the level of perceived stress was particularly high. For Russia only, we had
      information about heart function based on a 24 h ambulatory electrocardiogram;
      perceived stress was consistently associated with heart rate dysregulation in
      Russian men and women.

PMID- 23534871
TI  - Using Portable Health Information Kiosk to assess chronic disease burden in
      remote settings.
AB  - INTRODUCTION: Cancer, cardiovascular disease, chronic respiratory disease, and
      type 2 diabetes, are responsible for over 50% of worldwide mortality. Chronic
      diseases have broad negative impacts in developing countries. Contributing to the
      development of chronic diseases are sedentary lifestyles, poor nutrition and
      eating habits, and air pollution, among other risk factors. These are also
      greatly increasing, and obesity has become a global phenomenon. Health promotion,
      and chronic disease prevention and surveillance, can be achieved through
      information and communication technologies (ICT), which acquire, disseminate and
      store health-related information electronically. The portable health information
      kiosk (PHIK) can be a powerful tool for promoting health education in communities
      in both urban and rural settings. The objective of the study was to utilize a
      PHIK as a tool to assess the burden of chronic disease and associated risk
      factors in diverse settings in India. METHODS: A convenience sample was enrolled
      from three diverse geographical locations including urban, rural and tribal to
      explore the utilization of a PHIK for chronic disease health risk assessment in a
      community setting. Cross-sectional data was recorded during the period of March
      May 2010 in Rourkela and Bhubaneswar in the state of Orissa, India. Participants
      were asked to use a touch screen, electronic kiosk that gathered subjective and
      objective data to understand the burden of chronic diseases and associated risk
      in the community setting. The subjective data included responses to a series of
      multiple-choice questions and the objective data was gathered using multiple
      physiological sensors such as weight, blood sugar and blood pressure. Descriptive
      analysis was performed using univariate statistics with results for the
      continuous variables being reported as means and standard deviations while
      results for the categorical variables were reported as frequency statistics as
      appropriate. RESULTS: A total of 429 participants aged 18 years and older were
      enrolled in three different community settings: urban, slum and tribal.
      Significant differences were seen in the systolic blood pressure of those living
      in the urban settings as compared with those living in either slum
      (<i>p</i>=0.04) or tribal settings (<i>p</i>=0.02). Significant differences in
      the blood sugar levels were seen only among those living in the tribal as
      compared with the urban settings (<i>p</i>=0.04). Results showed high prevalence
      of pre-hypertension, stages 1 and 2 hypertension among those living in the slum
      and tribal settings. CONCLUSIONS: The results show the presence of chronic
      diseases in tribal and slum communities. The assessment of chronic health
      conditions in these populations is insufficient. Poor infrastructure and lack of
      qualified personnel are challenges to providing a meaningful service, as low
      wages, poor living and working conditions are obstacles that prevent the trained
      workforce from establishing themselves in these areas of extreme need. Health
      kiosks can be a multifaceted solution, as they can be used to assess health
      outcomes in areas that normally are not covered due to lack of infrastructure or
      health personnel, to establish health education modules and inform the local
      population about them. They can support evidence-based decisions for national and
      regional programs and policies.

PMID- 23534872
TI  - Causality and headache triggers.
AB  - OBJECTIVE: The objective of this study was to explore the conditions necessary to
      assign causal status to headache triggers. BACKGROUND: The term "headache
      trigger" is commonly used to label any stimulus that is assumed to cause
      headaches. However, the assumptions required for determining if a given stimulus
      in fact has a causal-type relationship in eliciting headaches have not been
      explicated. METHODS: A synthesis and application of Rubin's Causal Model is
      applied to the context of headache causes. From this application, the conditions
      necessary to infer that 1 event (trigger) causes another (headache) are outlined
      using basic assumptions and examples from relevant literature. RESULTS: Although
      many conditions must be satisfied for a causal attribution, 3 basic assumptions
      are identified for determining causality in headache triggers: (1) constancy of
      the sufferer, (2) constancy of the trigger effect, and (3) constancy of the
      trigger presentation. A valid evaluation of a potential trigger's effect can only
      be undertaken once these 3 basic assumptions are satisfied during formal or
      informal studies of headache triggers. CONCLUSIONS: Evaluating these assumptions
      is extremely difficult or infeasible in clinical practice, and satisfying them
      during natural experimentation is unlikely. Researchers, practitioners, and
      headache sufferers are encouraged to avoid natural experimentation to determine
      the causal effects of headache triggers. Instead, formal experimental designs or
      retrospective diary studies using advanced statistical modeling techniques
      provide the best approaches to satisfy the required assumptions and inform causal
      statements about headache triggers.

PMID- 23534874
TI  - Intraoperative radiotherapy of early breast cancer using low-kilovoltage x-rays
      reasons for omission of planned intraoperative irradiation.
AB  - The purpose of this study is to investigate reasons for omission of a planned
      intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS).
      Between 2002 and 2009, in 297 women an IORT during BCS was planned. In 55 women
      this irradiation was finally not performed. We retrospectively analyzed pre-,
      peri-, and postoperative data of these 55 women. Main reasons for omission of an
      IORT were insufficient tumor-skin distance (n = 20, 35.1%), an oversized wound
      cavity (n = 14, 24.6%), and a combination of both (n = 8, 14%). Further reasons
      (n = 12, 21.1%) were temporal shortage, unplanned maintenance work of the
      Intrabeam((r)) device, unsuitable anatomicosurgical conditions, and ineligible
      histologic findings. Apart from suitable anatomic conditions, a precise
      preoperative ultrasonography as well as a strict interdisciplinary preoperative
      management is important for successful application of IORT.

PMID- 23534873
TI  - Kinetics of adeno-associated virus serotype 2 (AAV2) and AAV8 capsid antigen
      presentation in vivo are identical.
AB  - Adeno-associated viral (AAV) vectors 2 and 8 have been used in clinical trials
      for patients with hemophilia, and data suggest that the capsid-specific CD8+ T
      cell response has had a negative impact on therapeutic success. To date the
      pattern of capsid cross-presentation from AAV2 and AAV8 transduction in vivo has
      not been elucidated. Previously, we have demonstrated that an engineered AAV2
      virus carrying the immune-dominant SIINFEKL peptide in the capsid backbone was
      indistinguishable from wild type with respect to titer, tropism, and the ability
      to induce capsid-specific CD8+ T cell responses in vivo. In this study, we used
      the same strategy to engineer an AAV8 vector and demonstrated that antigen from
      SIINFEKL peptide-integrated AAV8 capsid was effectively presented via either
      plasmid transfection or AAV8 transduction in vitro. The tissue tropism and
      transgene expression kinetics of the engineered AAV8 vector in vivo were
      identical to that of wild-type AAV8. Animal studies show that capsid antigen
      presentation from AAV transduction was dose dependent, and more importantly, the
      proliferation of capsid-specific CD8+ T cells had similar kinetics (detectable
      before 30 days and undetectable after 40 days) for both AAV2 and AAV8 vectors.
      Elucidation of the kinetics of capsid antigen presentation from AAV transduction
      by various serotypes provides new insight into the potential impact CD8+ T cells
      can have during clinical trials and may help with rational design of effective
      strategies to prevent capsid-specific CD8+ T cell-mediated elimination of AAV
      transduced target cells.

PMID- 23534875
TI  - Biphasic assembly of the contractile apparatus during the first two cell division
      cycles in zebrafish embryos.
AB  - The large and optically clear embryos of the zebrafish provide an excellent model
      system in which to study the dynamic assembly of the essential contractile band
      components, actin and myosin, via double fluorescent labelling in combination
      with confocal microscopy. We report the rapid appearance (i.e. within <2 min) of
      a restricted arc of F-actin patches along the prospective furrow plane in a
      central, apical region of the blastodisc cortex. These patches then fused with
      each other end-to-end forming multiple actin cables, which were subsequently
      bundled together forming an F-actin band. During this initial assembly phase, the
      F-actin-based structure did not elongate laterally, but was still restricted to
      an arc extending ~15 degrees  either side of the blastodisc apex. This initial
      assembly phase was then followed by an extension phase, where additional F-actin
      patches were added to each end of the original arc, thus extending it out to the
      edges of the blastodisc. The dynamics of phosphorylated myosin light chain 2
      (MLC2) recruitment to this F-actin scaffold also reflect the two-phase nature of
      the contractile apparatus assembly. MLC2 was not associated with the initial F
      actin arc, but MLC2 clusters were recruited and assembled into the extending ends
      of the band. We propose that the MLC2-free central region of the contractile
      apparatus acts to position and then extend the cleavage furrow in the correct
      plane, while the actomyosin ends alone generate the force required for furrow
      ingression. This biphasic assembly strategy may be required to successfully
      divide the early cells of large embryos.

PMID- 23534876
TI  - Scoring of sweat losses in exercised horses--a pilot study.
AB  - Based on a series of exercise tests which included the estimation of sweat
      losses, this article proposes a novel sweat scoring system for exercising horses.
      This provides a practical estimate of individual animal exercise-induced sweat
      losses, based on visible appearance of sweat on the coat after work, which takes
      into account the effect of various influencing factors. In terms of accuracy and
      flexibility, the score seems to provide advantages over estimates based on
      current general recommendations from reference books. Additional studies are
      needed to validate this scoring system and its use under more diverse situations.

PMID- 23534877
TI  - Treatment for life for severe haemophilia A- A cost-utility model for prophylaxis
      vs. on-demand treatment.
AB  - Prophylaxis has been established as the treatment of choice in children with
      haemophilia and its continuation into the adult years has been shown to decrease
      morbidity throughout life. The cost of factor therapy has made the option
      questionable in cost-effectiveness studies. The role of prophylaxis in
      pharmacokinetic dosage and tolerization against inhibitor formation were used to
      model the cost utility of prophylaxis vs. on-demand (OD) therapy over a lifetime
      horizon in severe haemophilia A. The model was applied to a single provider
      national health system exemplified by the United Kingdom's National Health
      Service and a third party provider in the United States. The incremental cost
      effectiveness ratio (ICER) was estimated and compared to threshold values used by
      payer agencies to guide reimbursement decisions. A cost per quality-adjusted life
      year (QALY) was also estimated for Sweden. Prophylaxis was dominant over OD
      treatment in the UK. The model resulted in an ICER - $68 000 - within the range
      of treatments reimbursed in the USA. In Sweden, a cost/QALY of SEK 1.1 million
      was also within the range of reimbursed treatments in that country. Dosage- and
      treatment-induced inhibitor incidence were the most important variables in the
      model. Subject to continuing clinical evidence of the effectiveness of
      pharmacokinetic dosage and the role of prophylaxis in decreasing inhibitor
      incidence, treatment for life with prophylaxis is a cost-effective therapy, using
      current criteria for the reimbursement of health care technologies in a number of
      countries.

PMID- 23534878
TI  - Long-term evaluation of donor-site morbidity after radial forearm flap
      phalloplasty for transsexual men.
AB  - INTRODUCTION: Phalloplasty using the radial forearm flap is currently the most
      frequently used technique to create the neophallus in transsexual men (formerly
      described as female-to-male transsexual persons). Although it is considered the
      gold standard, its main disadvantage is the eventual donor-site morbidity in a
      young, healthy patient population. AIM: The study aims to examine the long-term
      effects of radial forearm flap phalloplasty in transsexual men and to evaluate
      aesthetic outcome, scar acceptance, bone health, and daily functioning. MAIN
      OUTCOME MEASURES: Scars were evaluated with the patient and observer scar
      assessment scale, the Vancouver Scar Scale, and self-reported satisfaction. Bone
      health was assessed using dual X-ray absorptiometry and peripheral quantitative
      computed tomography, and daily functioning using a physical activity
      questionnaire (Baecke). These measurements were compared with 44 age-matched
      control women. METHODS: This is a cross-sectional study of 44 transsexual, a
      median of 7 years after radial forearm flap phalloplasty, recruited from the
      Center for Sexology and Gender Problems at the Ghent University Hospital,
      Belgium. RESULTS: We observed no functional limitations on daily life activities,
      a pain-free and rather aesthetic scar, and unaffected bone health a median of 7
      years after radial foreram flap phalloplasty. Over 75% of transsexual men were
      either satisfied or neutral with the appearance of the scar. CONCLUSIONS:
      Transsexual men, despite scarring the forearm, consider the radial forearm flap
      phalloplasty as worthwhile.

PMID- 23534879
TI  - Foliar uptake of fog water and transport belowground alleviates drought effects
      in the cloud forest tree species, Drimys brasiliensis (Winteraceae).
AB  - Foliar water uptake (FWU) is a common water acquisition mechanism for plants
      inhabiting temperate fog-affected ecosystems, but the prevalence and consequences
      of this process for the water and carbon balance of tropical cloud forest species
      are unknown. We performed a series of experiments under field and glasshouse
      conditions using a combination of methods (sap flow, fluorescent apoplastic
      tracers and stable isotopes) to trace fog water movement from foliage to
      belowground components of Drimys brasiliensis. In addition, we measured leaf
      water potential, leaf gas exchange, leaf water repellency and growth of plants
      under contrasting soil water availabilities and fog exposure in glasshouse
      experiments to evaluate FWU effects on the water and carbon balance of D.
      brasiliensis saplings. Fog water diffused directly through leaf cuticles and
      contributed up to 42% of total foliar water content. FWU caused reversals in sap
      flow in stems and roots of up to 26% of daily maximum transpiration. Fog water
      transported through the xylem reached belowground pools and enhanced leaf water
      potential, photosynthesis, stomatal conductance and growth relative to plants
      sheltered from fog. Foliar uptake of fog water is an important water acquisition
      mechanism that can mitigate the deleterious effects of soil water deficits for D.
      brasiliensis.

PMID- 23534880
TI  - The effect of body condition on propofol requirement in dogs.
AB  - OBJECTIVE: To determine if body condition score (BCS) influences the sedative
      effect of intramuscular (IM) premedication or the dose of intravenous (IV)
      propofol required to achieve endotracheal intubation in dogs. STUDY DESIGN:
      Prospective clinical study. ANIMALS: Forty-six client-owned dogs undergoing
      general anaesthesia. METHODS: Dogs were allocated to groups according to their
      BCS (BCS, 1 [emaciated] to 9 [obese]): Normal-weight Group (NG, n = 25) if BCS 4
      5 or Over-weight Group (OG, n = 21) if BCS over 6. Dogs were scored for sedation
      prior to IM injection of medetomidine (5 MUg kg(-1) ) and butorphanol (0.2 mg kg(
      1) ) and twenty minutes later anaesthesia was induced by a slow infusion of
      propofol at 1.5 mg kg(-1)  minute(-1) until endotracheal intubation could be
      achieved. The total dose of propofol administered was recorded. Data were tested
      for normality then analyzed using Student t-tests, Mann-Whitney U tests, chi
      square tests or linear regression as appropriate. RESULTS: Mean ( +/- SD)
      propofol requirement in NG was 2.24 +/- 0.53 mg kg(-1) and in OG was 1.83 +/-
      0.36 mg kg(-1) . The difference between the groups was statistically significant
      (p = 0.005). The degree of sedation was not different between the groups (p =
      0.7). Post-induction apnoea occurred in 11 of 25 animals in the NG and three of
      21 in OG (p = 0.052). CONCLUSIONS: Overweight dogs required a lower IV propofol
      dose per kg of total body mass to allow tracheal intubation than did normal body
      condition score animals suggesting that IV anaesthetic doses should be calculated
      according to lean body mass. The lower dose per kg of total body mass may have
      resulted in less post-induction apnoea in overweight/obese dogs. The effect of IM
      premedication was not significantly affected by the BCS. CLINICAL RELEVANCE:
      Induction of general anaesthesia with propofol in overweight dogs may be expected
      at lower doses than normal-weight animals.

PMID- 23534881
TI  - Comparative proteomic analysis and IgE binding properties of peanut seed and
      testa (skin).
AB  - To investigate the protein composition and potential allergenicity of peanut
      testae or skins, proteome analysis was conducted using nanoLC-MS/MS sequencing.
      Initial amino acid analysis suggested differences in protein compositions between
      the blanched seed (skins removed) and skin. Phenolic compounds hindered analysis
      of proteins in skins when the conventional extraction method was used; therefore,
      phenol extraction of proteins was necessary. A total of 123 proteins were
      identified in blanched seed and skins, and 83 of the proteins were common between
      the two structures. The skins contained all of the known peanut allergens in
      addition to 38 proteins not identified in the seed. Multiple defense proteins
      with antifungal activity were identified in the skins. Western blotting using
      sera from peanut-allergic patients revealed that proteins extracted from both the
      blanched seed and skin bound significant levels of IgE. However, when phenolic
      compounds were present in the skin protein extract, no IgE binding was observed.
      These findings indicate that peanut skins contain potentially allergenic
      proteins; however, the presence of phenolic compounds may attenuate this effect. 

PMID- 23534882
TI  - Accurate prediction of disorder in protein chains with a comprehensive and
      empirically designed consensus.
AB  - Availability of computational methods that predict disorder from protein
      sequences fuels rapid advancements in the protein disorder field. The most
      accurate predictions are usually obtained with consensus-based approaches.
      However, their design is performed in an ad hoc manner. We perform first-of-its
      kind rational design where we empirically search for an optimal mixture of base
      methods, selected out of a comprehensive set of 20 modern predictors, and we
      explore several novel ways to build the consensus. Our method for the prediction
      of disorder based on Consensus of Predictors (disCoP) combines seven base
      methods, utilizes custom-designed set of selected 11 features that aggregate base
      predictions over a sequence window and uses binomial deviance loss-based
      regression to implement the consensus. Empirical tests performed on an
      independent benchmark set (with low-sequence similarity compared with proteins
      used to design disCoP), shows that disCoP provides statistically significant
      improvements with at least moderate magnitude of differences. disCoP outperforms
      28 predictors, including other state-of-the-art consensuses, and achieves Area
      Under the ROC Curve of .85 and Matthews Correlation Coefficient of .5 compared
      with .83 and .48 of the best considered approach, respectively. Our consensus
      provides high rate of correct disorder predictions, especially when low rate of
      incorrect disorder predictions is desired. We are first to comprehensively assess
      predictions in the context of several functional types of disorder and we
      demonstrate that disCoP generates accurate predictions of disorder located at the
      post-translational modification sites (in particular phosphorylation sites) and
      in autoregulatory and flexible linker regions. disCoP is available at
      http://biomine.ece.ualberta.ca/disCoP/.

PMID- 23534885
TI  - Desmopressin (DDAVP) improves recruitment of activated platelets to collagen but
      simultaneously increases platelet endothelial interactions in vitro.
AB  - Platelet dysfunction can cause clinically relevant bleeding. Treatment with DDAVP
      is advocated for this condition. DDAVP increases von Willebrand factor (VWF) on
      endothelial cells (ECs) and in plasma. VWF could facilitate platelet deposition
      on subendothelial collagen. VWF also facilitates platelet/EC interactions.
      Therefore DDAVP could precipitate thromboembolic events. We used a flow chamber
      model to study in vitro and ex vivo if DDAVP alters recruitment of platelets to
      EC and collagen. Resting or TRAP-activated platelets and EC were treated
      individually or simultaneously with 0.4 ng/ml DDAVP. Fluorophor-labeled platelets
      (10(6)/ml) were resuspended in reconstituted blood and superfused across EC and
      collagen in an in vitro flow chamber model at arterial shear (320 s(-1)).
      Adhesion of platelets to the respective surface was recorded fluorescence
      microscopically and platelet covered area was assessed. TRAP significantly
      induced adhesiveness of platelets for collagen and EC. DDAVP pretreatment of
      platelets did not affect adhesiveness of resting or TRAP-activated platelets for
      collagen or EC. Adhesiveness of resting but not TRAP-activated platelets was
      induced on DDAVP-treated EC. DDAVP-conditioned EC supernatant contained vWF and
      significantly increased platelet deposition on collagen. Platelets from patients
      with clinically suspected platelet dysfunction undergoing aortic valve
      replacement exhibited decreased platelet deposition on collagen surfaces. In
      summary, our data confirm that DDAVP can induce release of platelet adhesion
      promoting factors from EC, which is most likely vWF. DDAVP has no direct effect
      on platelets. Blood samples from DDAVP-treated patients do not exhibit
      significantly augmented platelet deposition on collagen ex vivo. This influence
      of released promoting factors might cause an increase of undesirable interactions
      of platelets with EC.

PMID- 23534883
TI  - Citrate-capped silver nanoparticles showing good bactericidal effect against both
      planktonic and sessile bacteria and a low cytotoxicity to osteoblastic cells.
AB  - A common problem with implants is that bacteria can form biofilms on their
      surfaces, which can lead to infection and, eventually, to implant rejection. An
      interesting strategy to inhibit bacterial colonization is the immobilization of
      silver (Ag) species on the surface of the devices. The aim of this paper is to
      investigate the action of citrate-capped silver nanoparticles (AgNPs) on
      clinically relevant Gram-positive (Staphylococcus aureus) and Gram-negative
      (Pseudomonas aeruginosa) bacteria in two different situations: (i) dispersed
      AgNPs (to assess the effect of AgNPs against planktonic bacteria) and (ii)
      adsorbed AgNPs on titanium (Ti) substrates, a material widely used for implants
      (to test their effect against sessile bacteria). In both cases, the number of
      surviving cells was quantified. The small amount of Ag on the surface of Ti has
      an antimicrobial effect similar to that of pure Ag surfaces. We have also
      investigated the capability of AgNPs to kill planktonic bacteria and their
      cytotoxic effect on UMR-106 osteoblastic cells. The minimum bactericidal
      concentration found for both strains is much lower than the AgNP concentration
      that leads to cytotoxicity to osteoblasts. Planktonic P. aeruginosa show a higher
      susceptibility to Ag than S. aureus, which can be caused by the different wall
      structures, while for sessile bacteria, similar results are obtained for both
      strains. This can be explained by the presence of extracellular polymeric
      substances in the early stages of P. aeruginosa biofilm formation. Our findings
      can be important to improving the performance of Ti-based implants because a good
      bactericidal action is obtained with very small quantities of Ag, which are not
      detrimental to the cells involved in the osseointegration process.

PMID- 23534886
TI  - Determination of corner positions for calculation of step height of atomic force
      microscope images based on ISO 5436-1.
AB  - Step height is defined as the vertical spacing between two plane-parallel planes
      comprising an elevation or an indentation and the substrate. In atomic force
      microscopy (AFM), there are many algorithms for determining feature dimensions
      such as step height and width. One common problem of many algorithms is the
      difficulty for users to accurately determine the corner positions needed to
      properly implement the said algorithms. A new algorithm based on ISO 5436-1 is
      proposed that determines the necessary corner positions along with two examples
      illustrating the implementation of this algorithm. We propose calling this new
      method the determinant method. Since the corner positions are automatically
      decided, feature dimensions such as step height of an AFM image are easily
      determined. Comparative experiments carried out to compare the step height
      measurement using this algorithm and the SPIP software from Image Metrology show
      encouraging results.

PMID- 23534887
TI  - Migraine-like accompanying features in patients with cluster headache. How
      important are they?
AB  - BACKGROUND: According to the International Classification of Headache Disorders
      diagnostic criteria, the differences between migraine and cluster headache (CH)
      are clear. In addition to headache attack duration and pain characteristics, the
      symptoms accompanying headache represent the key features in a differential
      diagnosis of these 2 primary headache disorders. Just a few studies of patients
      with CH exist examining the presence of nausea, vomiting, photophobia,
      phonophobia, and aura, the features commonly accompanying migraine headache. The
      aim of this study was to determine the presence of migraine-like features (MF) in
      patients with CH and establish the significance of these phenomena related to
      other clinical features and response to treatment. METHODS: One hundred and fifty
      five patients with CH were studied, and 24.5% of them experienced at least one of
      MF during every CH attack. Nausea and vomiting were the most frequently reported
      MF. The clinical presentation between CH patients with and without MF was not
      significantly different with the exception of aggravation of pain by effort
      (20.6% vs 4.1%) and facial sweating (13.2% vs 0.85%), both more frequent in CH
      patients with MF. CONCLUSION: Inferred from the results of our study, the
      presence of MF in CH patients had no important influence on the diagnosis and
      treatment of CH patients. The major differences of these 2 primary headache
      disorders, attack duration, lateralization, and the nature of associated
      symptoms, as delineated in the International Classification of Headache
      Disorders, are still useful tools for effective diagnosis.

PMID- 23534888
TI  - Cognitive and emotional determinants characterizing women with persistent genital
      arousal disorder.
AB  - INTRODUCTION: Persistent genital arousal disorder (PGAD) is a relatively unknown
      clinical condition affecting several women. Moral standards, as well as
      conservative beliefs regarding sexuality, are believed to be involved in the
      etiology and maintenance of this syndrome. Nevertheless, there are no consistent
      data on the content of the beliefs system presented by these women. AIM: The aim
      of this study was to characterize the cognitive and emotional style of women
      reporting PGAD. More precisely, the content of sexual beliefs, thoughts, and
      emotions during sexual intercourse was explored. METHODS: Forty-three women
      presenting PGAD and 42 controls responded to a web survey. This study was cross
      cultural in nature and women worldwide (over 18 years old) were asked to
      participate. MAIN OUTCOME MEASURES: Participants answered the following online
      questionnaires: Sexual Dysfunctional Beliefs Questionnaire, Sexual Modes
      Questionnaire, Positive and Negative Affect Schedule, and Brief Symptom
      Inventory. Additionally, participants responded to a checklist assessing the
      presence and frequency of PGAD symptoms. RESULTS: After controlling for
      sociodemographic characteristics and psychopathology, findings showed that women
      reporting PGAD symptoms presented significantly more dysfunctional sexual beliefs
      (e.g., sexual conservatism, sexual desire as a sin), as well as more negative
      thoughts (e.g., thoughts of sexual abuse and of lack of partner's affection) and
      dysfunctional affective states (more negative and less positive affect) during
      sexual activity than non-PGAD women. CONCLUSIONS: Notwithstanding the impact of
      neurophysiological determinants in the etiology of this syndrome, results support
      the psychological conceptualization of PGAD and highlight the role of cognitive
      behavioral therapy (CBT) for PGAD symptomatology. More specifically, cognitive
      and behavioral strategies would be aimed at targeting maladaptive sexual beliefs
      and thoughts, as well as regulating negative affective states resulting from a
      dysfunctional cognitive style regarding sexuality. In all, CBT in association
      with a medical/pharmacological approach, could be clinically relevant in the
      management of PGAD.

PMID- 23534889
TI  - Quantitative analysis of uranium in aqueous solutions using a semiconductor laser
      based spectroscopic method.
AB  - A simple analytical method based on the simultaneous measurement of the
      luminescence of hexavalent uranium ions (U(VI)) and the Raman scattering of
      water, was investigated for determining the concentration of U(VI) in aqueous
      solutions. Both spectra were measured using a cw semiconductor laser beam at a
      center wavelength of 405 nm. The empirical calibration curve for the quantitative
      analysis of U(VI) was obtained by measuring the ratio of the luminescence
      intensity of U(VI) at 519 nm to the Raman scattering intensity of water at 469
      nm. The limit of detection (LOD) in the parts per billion range and a dynamic
      range from the LOD up to several hundred parts per million were achieved. The
      concentration of uranium in groundwater determined by this method is in good
      agreement with the results determined by kinetic phosphorescence analysis and
      inductively coupled plasma mass spectrometry. 

PMID- 23534890
TI  - Recovery from azoospermia caused by a testicular injury: a case report.
AB  - Some cases of testicular trauma cause infertility especially when the injured
      testes are not removed. However, only a few long-term follow-up studies
      investigating endocrinological and semen parameters in patients who had
      testicular trauma have been conducted. Herein, we report an interesting case of a
      patient who spontaneously recovered from azoospermia due to a traffic injury and
      present in detail the results of the hormonal examination and semen analysis. The
      patient was a 22-year-old man with a history of left testicular injury and
      bilateral orchidopexy. Four months after the injury, the semen parameters
      improved but azoospermia occurred 1 year later. However, spermatogenesis
      spontaneously recovered without any treatment or without undergoing orchiectomy 6
      months after the testicular injury. 

PMID- 23534891
TI  - Comparing urban and rural young adult cancer survivors' experiences: a
      qualitative study.
AB  - INTRODUCTION: Large administrative data set analyses demonstrate that geography
      has a significant impact on access to health care and subsequent health outcomes.
      In general, rural populations have poorer access to healthcare services. This
      article explores the reality of this issue for young adult cancer survivors.
      METHODS: Data was of a subset of 30 participants from a larger qualitative study
      that examined cancer survivorship issues for young adult cancer patients in
      Canada. The subset of participants are from New Brunswick, a predominantly rural
      province in Eastern Canada with a population of 750,000 spread out over a large
      geographical area, and from Canada's largest metropolis center, Greater Toronto
      Area, with a population of around 6 million. RESULTS: Analysis of the qualitative
      data using constructivist grounded theory revealed several expected and
      unexpected differences between the two geographically distinct groups. The rural
      group of young adult cancer survivors reported more frequent episodes of delayed
      diagnosis and lower levels of community support compared to the urban
      participants. The urban young adult cancer survivors discussed out-of-pocket
      expenses for cancer treatment more often than the rural participants. Many rural
      participants made it clear that they were keenly aware that not all cancer care
      services were readily available where they lived, and yet they reported
      considerably higher levels of satisfaction with the cancer care that they
      received than the urban participants. CONCLUSION: Despite the lack of important
      cancer services in rural areas, rural young adult cancer survivors expressed
      higher levels of satisfaction with their care than did urban cancer survivors. It
      appears that levels of satisfaction are related to expectations. Rural
      participants were aware of the more limited services available and felt that
      their cancer care practitioners provided the best care possible given the limited
      resources. Urban participants may have higher expectations of cancer care and
      felt that the cancer care they received fell below expectations. In the future,
      researchers may want to focus on cancer care expectations, satisfaction levels
      and psychosocial outcomes in greater detail.

PMID- 23534892
TI  - Evaluation of land use regression models for NO2 and particulate matter in 20
      European study areas: the ESCAPE project.
AB  - Land use regression models (LUR) frequently use leave-one-out-cross-validation
      (LOOCV) to assess model fit, but recent studies suggested that this may
      overestimate predictive ability in independent data sets. Our aim was to evaluate
      LUR models for nitrogen dioxide (NO2) and particulate matter (PM) components
      exploiting the high correlation between concentrations of PM metrics and NO2. LUR
      models have been developed for NO2, PM2.5 absorbance, and copper (Cu) in PM10
      based on 20 sites in each of the 20 study areas of the ESCAPE project. Models
      were evaluated with LOOCV and "hold-out evaluation (HEV)" using the correlation
      of predicted NO2 or PM concentrations with measured NO2 concentrations at the 20
      additional NO2 sites in each area. For NO2, PM2.5 absorbance and PM10 Cu, the
      median LOOCV R(2)s were 0.83, 0.81, and 0.76 whereas the median HEV R(2) were
      0.52, 0.44, and 0.40. There was a positive association between the LOOCV R(2) and
      HEV R(2) for PM2.5 absorbance and PM10 Cu. Our results confirm that the
      predictive ability of LUR models based on relatively small training sets is
      overestimated by the LOOCV R(2)s. Nevertheless, in most areas LUR models still
      explained a substantial fraction of the variation of concentrations measured at
      independent sites.

PMID- 23534893
TI  - Focal extravasated mucin in breast core needle biopsies: is surgical excision
      always necessary?
AB  - Focal extravasated mucin (EM) with benign or atypical epithelium is a rare
      finding at breast core needle biopsy (CNB) and usually prompts surgical excision
      to rule out mucin-producing carcinoma. In the largest detailed series to date, we
      assessed surgical outcomes in lesions yielding EM with atypical or nonatypical
      epithelium at CNB. With IRB approval, we retrospectively reviewed 28 consecutive
      atypical and nonatypical CNBs with EM that underwent surgical excision at our
      center over a 22-year period. CNB imaging and pathologic findings were concordant
      if pathology sufficiently explained the radiologic features of the lesions.
      Pathologic findings in CNB and excision specimens were correlated. Statistical
      analysis was performed. CNBs sampled mammographic calcifications in 25/28 (89%)
      women and a mass in 3/28 (11%). All cases had concordant pathologic and imaging
      findings. At CNB, the epithelium associated with EM was atypical in 18/28 (64%)
      lesions and nonatypical in 10 (36%). Cancer (one mucinous carcinoma; three ductal
      carcinoma in situ) was present in 4/28 excision specimens (14%; 95% confidence
      intervals [CI], 4%-33%). All carcinomas were in lesions with epithelial atypia at
      CNB (4/18; 22%; 95% CI, 6%-48%) versus none (0/10; 0%; 95% CI, 0%-31%) in
      nonatypical lesions at CNB; this difference was not statistically significant (p
      = 0.3). Surgery is warranted for lesions yielding EM with atypia at CNB due to
      the high (22%) prevalence of cancer. Our data suggest that surgical excision of
      lesions yielding EM without epithelial atypia at CNB may not be necessary
      provided that imaging and pathologic findings are concordant.

PMID- 23534895
TI  - 1,3-Diketone fluids and their complexes with iron.
AB  - Tribological experiments with 1,3-diketone fluids in contact with iron surfaces
      show ultralow friction, which was suggested to be connected to the formation of
      iron complexes. In order to support this assumption, we calculate infrared and
      optical spectra of various substituted 1,3-diketones and their iron complexes
      using gradient-corrected density functional theory (DFT). The description of the
      complexes requires the application of the DFT+U scheme for a correct prediction
      of the high spin state on the central iron atom. With this approach, we obtain
      excellent agreement between experiment and simulation in infrared and optical
      spectra, allowing for the determination of 1,3-diketone tautomeric forms. The
      match in the spectra of the complex strongly supports the assumption of iron
      complex formation by these lubricants.

PMID- 23534894
TI  - Radioactive synovectomy with (90) yttrium and (153) samarium hydroxyapatite in
      haemophilic joints: preliminary study on radiation safety.
AB  - Most countries still do not achieve 1 IU of factor VIII/capita sufficient for
      survival. Although primary prophylaxis prevents synovitis, is not universally
      used. Chronic synovitis is treated with arthroscopy at expense of considerable
      amount of coagulation factors, and specialized surgeons. Radioactive synovectomy
      (RS) is a minimally invasive and cost effective alternative to arthroscopy, often
      considered first the option for persistent synovitis. Even without established
      causation with cancer, RS is avoided by some, due to this concern. We aim
      contributing to the understanding of RS safety regarding malignancy, presenting a
      large number of treated patients, and a single case of cancer. Three centres in
      Brazil applied RS with (90) Yttrium Citrate, (90) Yttrium hydroxyapatite or (153)
      Samarium hydroxyapatite in haemophilic joints and performed a survey addressing
      cancer in these patients. Four hundred and eighty eight patients (ages 3-51)
      received 1-3 RS (total 842) and follow-up was 6 months to 9 years. One patient
      aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated
      successfully with surgery and chemotherapy. Causality of cancer by RS is
      improbable in this case. Accordingly, latency here is far below minimum 5-10
      years for radio-induction of solid tumours. Moreover, ES is not a typically radio
      induced tumour, even at high doses. In agreement with others, though recognizing
      limitations, this study suggests RS is safe regarding cancer induction. Synovitis
      is a known burden for patients. The decision of making reasonable usage of RS
      should be outweighed with the risks of leaving synovitis untreated.

PMID- 23534896
TI  - Comparison of the efficacy of fexofenadine 120 and 240 mg/day on chronic
      idiopathic urticaria and histamine-induced skin responses in Japanese
      populations.
AB  - BACKGROUND: H1-antihistamines are the first-line treatment of chronic idiopathic
      urticaria (CIU), but CIU is occasionally refractory to the conventional treatment
      doses. Guidelines in Europe recommend increasing doses as second-line therapy;
      however, more supportive evidences for these guidelines are required to justify
      this management strategy. METHODS: In this study, the authors evaluated the
      effect of conventional and double doses of fexofenadine HCl on CIU and on
      histamine-induced skin responses by iontophoresis using visual and laser Doppler
      imaging scales in healthy donors. RESULTS: Cutaneous manifestations in CIU and
      histamine-induced flare and itch in healthy donors were attenuated more
      extensively by a double dose of fexofenadine HCl compared with a conventional
      dose. CONCLUSION: The above findings support the management strategy that
      increasing the dose of non-sedative antihistamines is the second-line treatment
      choice for refractory CIU even in Japanese populations.

PMID- 23534897
TI  - Consumer acceptability and understanding of front-of-pack nutrition labels.
AB  - BACKGROUND: Front-of-pack (FOP) nutrition labelling has been proposed as a tool
      for helping consumers make healthy choices. Before determining its effects on
      consumer behaviour, factors involved in its use must be elucidated, i.e.
      understanding and acceptability on the part of the consumer. Among five FOP
      labels, we sought to determine which formats were most easily understood and
      accepted by a large sample of adults. METHODS: Among 39 370 adults who
      participated in the French Nutrinet-Sante cohort study, understanding and
      indicators of acceptability (attitude, liking, visual attractiveness and
      perceived cognitive workload) were measured for five FOP labels: The currently
      used 'multiple traffic lights' (MTL) and 'simple traffic lights' (STL), and the
      'colour range' logo (CR), the 'green tick' and the PNNS logo. We investigated the
      contribution of the different elements to consumer perception of FOP labels using
      multiple correspondence analyses. RESULTS: Over half of the sample population
      showed a high level of understanding and perceived no discomfort in terms of the
      different logos. Label formats were positioned along an acceptability gradient
      ranging from acceptance to rejection, consisting of 'liking', 'attractiveness'
      and indicators of perceived cognitive workload. MTL was significantly more often
      liked and was viewed as reliable and informative. MTL, STL and the green tick
      performed better than the CR and PNNS logos in terms of ease of identification
      and comprehension. CR was clearly the least appreciated and it had the most
      complex format. CONCLUSIONS: Consumers prefer FOP labels which give complete,
      reliable and simplified information on the nutrient quality of foods.

PMID- 23534898
TI  - Raman scattering at plasmonic junctions shorted by conductive molecular bridges.
AB  - Intensity spikes in Raman scattering, accompanied by switching between line
      spectra and band spectra, can be assigned to shorting the junction plasmon
      through molecular conductive bridges. This is demonstrated through Raman
      trajectories recorded at a plasmonic junction formed by a gold AFM tip in contact
      with a silver surface coated either with biphenyl-4,4'-dithiol or biphenyl-4
      thiol. The fluctuations are absent in the monothiol. In effect, the making and
      breaking of chemical bonds is tracked.

PMID- 23534899
TI  - Stages in the early and larval development of the African catfish Clarias
      gariepinus (Teleostei, Clariidae).
AB  - The African catfish Clarias gariepinus Burchell 1822 is a favourite aquaculture
      fish in many parts of Africa and Asia because of its hardiness and fast growth
      rate. In this study, early, post-embryonic and larval developmental stages of C.
      gariepinus were examined chronologically and described. Photomicrographs of
      unfertilized matured oocytes from 0 min of fertilization through all cell stages
      to alevin, to complete yolk absorption, to free swimming larval stages are shown
      and documented live from lateral and top views, with the aid of a light
      microscope. Extruded oocytes had a mean diameter of 1 +/- 0.1 mm, and possessed a
      thin perivitelline membrane whose space was filled with a protoplasmic layer.
      Heartbeat was in the range of 115-160/min prior to hatching. Hatchability rate
      was 85% and hatching occurred at 17 h at a controlled temperature of 28.5 +/- 0.5
      degrees C, while ontogeny of the eyes and other organs were discernible. At day
      4, larvae mean length was 9.3 +/- 0.5 mm, exogenous feeding had commenced fully
      and melanophores spread cephalocaudally but were concentrated significantly on
      the head parts. This paper, for the first time, presents the significant
      chronological developmental stages of C. gariepinus embryology that will have
      significant implications for genetic manipulation and catfish seed production for
      aquaculture.

PMID- 23534900
TI  - Binding site dynamics and aromatic-carbohydrate interactions in processive and
      non-processive family 7 glycoside hydrolases.
AB  - In nature, processive and non-processive cellulase enzymes deconstruct cellulose
      to soluble sugars. From structural studies, the consensus is that processive
      cellulases exhibit tunnels lined with aromatic and polar residues, whereas non
      processive cellulases exhibit open clefts with fewer ligand contacts. To gain
      additional insight into the differences between processive and non-processive
      cellulases, we examine the glycoside hydrolase family 7 (GH7) cellobiohydrolase,
      Cel7A, and the endoglucanase, Cel7B, from Trichoderma reesei with molecular
      simulation. We compare properties related to processivity and compute the binding
      affinity changes for mutation of four aromatic residues lining the Cel7A active
      site tunnel and Cel7B cleft to alanine. For the wild-type enzymes, dissimilar
      behavior is observed at nearly every glucopyranose-binding site from -7 to +2,
      except in the -2 site, suggesting that the structural differences directly around
      the catalytic center and at the active site tunnel entrances and exits may all
      contribute to processivity in GH7s. Interestingly, the -2 site is similar in both
      enzymes, likely due to the significant conformational change needed in the
      cellodextrin ligand near this site for catalysis. Moreover, aromatic residue
      mutations in the Cel7A and Cel7B active sites display only small differences in
      binding affinity, but the ligand flexibility and enzyme-ligand interactions are
      only locally affected in Cel7A, whereas the entire ligand is significantly
      affected when any aromatic residue is mutated in Cel7B.

PMID- 23534901
TI  - Interventions designed to limit gestational weight gain: a systematic review of
      theory and meta-analysis of intervention components.
AB  - Limiting gestational weight gain (GWG) to recommended levels is important to
      optimize health outcomes for mother and baby. Surprisingly, a recent review
      revealed that theory-based interventions to limit GWG were less effective than
      interventions that did not report a theory-base; however, strict criteria were
      used to identify theory-informed studies. We extended this review and others by
      systematically evaluating the theories of behaviour change informing GWG
      interventions using a generalized health psychology perspective, and meta
      analysing behaviour change techniques reported in the interventions.
      Interventions designed to limit GWG were searched for using health, nursing and
      psychology databases. Papers reporting an underpinning theory were identified and
      the CALO-RE taxonomy was used to determine individual behaviour change
      techniques. Nineteen studies were identified for inclusion. Eight studies were
      informed by a behaviour change theory; six reported favourable effects on GWG.
      Overall, studies based on theory were as effective as non-theory-based studies at
      limiting GWG. Furthermore, the provision of information, motivational
      interviewing, behavioural self-monitoring and providing rewards contingent on
      successful behaviour appear to be key strategies when intervening in GWG.
      Combining these behaviour change techniques with dietary interventions may be
      most effective. Future research should focus on determining the exact combination
      of behaviour change techniques, or which underpinning theories, are most useful
      for limiting GWG.

PMID- 23534902
TI  - Protozoa enhance foraging efficiency of arbuscular mycorrhizal fungi for mineral
      nitrogen from organic matter in soil to the benefit of host plants.
AB  - Dead organic matter (OM) is a major source of nitrogen (N) for plants. The
      majority of plants support N uptake by symbiosis with arbuscular mycorrhizal (AM)
      fungi. Mineralization of N is regulated by microfauna, in particular, protozoa
      grazing on bacteria. We hypothesized that AM fungi and protozoa interactively
      facilitate plant N nutrition from OM. In soil systems consisting of an OM patch
      and a root compartment, plant N uptake and consequences for plant carbon (C)
      allocation were investigated using stable isotopes. Protozoa mobilized N by
      consuming bacteria, and the mobilized N was translocated via AM fungi to the host
      plant. The presence of protozoa in both the OM and root compartment stimulated
      photosynthesis and the translocation of C from the host plant via AM fungi into
      the OM patch. This stimulated microbial activity in the OM patch, plant N uptake
      from OM and doubled plant growth. The results indicate that protozoa increase
      plant growth by both mobilization of N from OM and by protozoa-root interactions,
      resulting in increased C allocation to roots and into the rhizosphere, thereby
      increasing plant nutrient exploitation. Hence, mycorrhizal plants need to
      interact with protozoa to fully exploit N resources from OM.

PMID- 23534903
TI  - Bringing a transgenic crop to market: where compositional analysis fits.
AB  - In the process of developing a biotechnology product, thousands of genes and
      transformation events are evaluated to select the event that will be
      commercialized. The ideal event is identified on the basis of multiple
      characteristics including trait efficacy, the molecular characteristics of the
      insert, and agronomic performance. Once selected, the commercial event is
      subjected to a rigorous safety evaluation taking a multipronged approach
      including examination of the safety of the gene and gene product - the protein,
      plant performance, impact of cultivating the crop on the environment, agronomic
      performance, and equivalence of the crop/food to conventional crops/food - by
      compositional analysis. The compositional analysis is composed of a comparison of
      the nutrient and antinutrient composition of the crop containing the event, its
      parental line (variety), and other conventional lines (varieties). Different
      geographies have different requirements for the compositional analysis studies.
      Parameters that vary include the number of years (seasons) and locations
      (environments) to be evaluated, the appropriate comparator(s), analytes to be
      evaluated, and statistical analysis. Specific examples of compositional analysis
      results will be presented. 

PMID- 23534904
TI  - Harvesting new therapeutic avenues with stem cell applications.

PMID- 23534905
TI  - TLR-mediated induction of proinflammatory cytokine IL-32 in corneal epithelium.
AB  - PURPOSE: IL-32, a newly discovered cytokine, has been associated with a variety
      of inflammatory diseases. The role of innate immunity in regulation of IL-32
      expression has not been elucidated. This study was to explore TLR-mediated
      induction of IL-32 and the inflammatory effects of IL-32 in corneal epithelium.
      METHODS: Human corneal tissues and primary human corneal epithelial cells (HCECs)
      were treated with a variety of viral or bacterial components, as well as IL-32
      without or with different TLR pathway inhibitors. The mRNA expression was
      determined by reverse transcription and real time PCR, and the protein levels
      were measured by ELISA and immunostaining. RESULTS: IL-32 mRNA and protein were
      largely induced by specific microbial components, including polyinosinic
      polycytidylic acid (polyI:C) and flagellin, the ligands to TLR3 and TLR5
      respectively, in human corneal epithelium ex vivo and in vitro cultures. The
      polyI:C-induced IL-32 production was blocked by TLR3 antibody or TRIF inhibitory
      peptide, while flagellin-stimulated IL-32 was blocked by TLR5 antibody or MyD88
      inhibitory peptide. Interestingly, IkappaB-alpha inhibitor (BAY11-7082) or
      nuclear factor kappa B (NF-kappaB) inhibitor (quinazoline) blocked NF-kappaB p65
      protein nuclear translocation, and also suppressed IL-32 production induced by
      polyI:C or flagellin. When HCECs were treated with IL-32, we observed its
      stimulatory affects on inflammatory cytokines, TNF-alpha, IL-1beta and IL-8, at
      both mRNA and protein levels. CONCLUSION: These findings demonstrate that IL-32
      is induced by microbial ligands through TLR-mediated innate signaling pathways,
      suggesting an important role of corneal epithelium in inflammatory disease.

PMID- 23534906
TI  - Oxycodone combined with opioid receptor antagonists: efficacy and safety.
AB  - INTRODUCTION: A mu receptor antagonist combined with oxycodone (OXY) may improve
      pain control, reduce physical tolerance and withdrawal, minimizing opioid-related
      bowel dysfunction and act as an abuse deterrent. AREAS COVERED: The authors cover
      the use of OXY plus ultra-low-dose naltrexone for analgesia and the use of
      sustained-release OXY plus sustained-release naloxone to reduce the opioid bowel
      syndrome. The authors briefly describe the use of sustained-release OXY and
      naltrexone pellets as a drug abuse deterrent formulation. Combinations of ultra
      low-dose naltrexone plus OXY have been in separate trials involved in patients
      with chronic pain from osteoarthritis and idiopathic low back pain. High
      attrition and marginal differences between ultra-low-dose naltrexone plus OXY and
      OXY led to discontinuation of development. Prolonged-release (PR) naloxone
      combined with PR OXY demonstrates a consistent reduction in opioid-related bowel
      dysfunction in multiple randomized controlled trials. However, gastrointestinal
      side effects, including diarrhea, were increased in several trials with the
      combination compared with PR OXY alone. Analgesia appeared to be maintained
      although non-inferiority to PR OXY is not formally established. There were flaws
      to trial design and safety monitoring. Naltrexone has been combined with OXY in
      individual pellets encased in a capsule. This combination has been reported in a
      Phase II trial and is presently undergoing Phase III studies. EXPERT OPINION: Due
      to the lack of efficacy the combination of altered low-dose naltrexone with
      oxycodone should cease in development. The combination of sustained release
      oxycodone plus naloxone reduces constipation with a consistent benefit. Safety
      has been suboptimally evaluated which is a concern. Although the drug is
      commercially available in several countries, ongoing safety monitoring
      particularly high doses would be important.

PMID- 23534907
TI  - Epidermodysplasia verruciformis in lipoid proteinosis: case report and discussion
      of pathophysiology.
AB  - Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by
      mutations in extracellular matrix protein 1 (ECM1) that involves deposition of
      basement membrane-like material in the skin and other organs. Epidermodysplasia
      verruciformis (EV) is also a rare autosomal recessive genodermatosis involving
      susceptibility to human papillomavirus (HPV) infections and squamous cell
      carcinoma, caused in most cases by homozygous mutations in EVER1 or EVER2. We
      describe a case of EV in a patient with LP and discuss the pathophysiology. A 3
      year-old Lebanese girl presented with hoarseness, beaded papules along the eyelid
      margins, waxy papules and plaques on her head and neck, and lichenoid verrucous
      papules on the forearms and hands. Histopathology of the waxy papules exhibited
      deposition of periodic acid Schiff-positive basement membrane-like material in
      the superficial dermis, characteristic of LP. The verruca plana-like lesions
      exhibited acanthosis and enlarged keratinocytes with pale blue-grey cytoplasm and
      a perinuclear halo, consistent with verrucae and EV. Polymerase chain reaction
      amplification and sequencing of ECM1, EVER1, and EVER2 demonstrated a homozygous
      point mutation, c.389C>T (p.Thr130Met), in exon 6 of ECM1 and a heterozygous
      point mutation, c.917 A>T (p.Asn306Ile), in exon 8 in EVER2, known to cause EV in
      homozygous patients. The homozygous point mutation c.389C>T in ECM1 may be a
      novel mutation causing LP. Verruca plana-like lesions seen in LP appear to
      represent a form of acquired EV. In this patient, a heterozygous mutation in
      EVER2 at c.917 A>T may also have conferred susceptibility to HPV infection. 

PMID- 23534908
TI  - Superior reaction to changing directions for skilled basketball defenders but not
      linked with specialised anticipation.
AB  - The purpose of the present study was to examine the timing for the detection of
      relevant information in the final running direction of attackers' cutting
      manoeuvres. Skilled basketball players and novices performed sidestep and reach
      tasks in response to a ready-go choice stimuli using light-emitting diode (LED)
      task and video stimuli (video task) wherein skilled ball players executed cutting
      manoeuvres. The time at which the defenders first obtained relevant visual
      information was estimated by subtracting the visuo-motor processing time,
      acquired from the reaction time in the LED task, from the reaction time in the
      video task. Skilled basketball players reacted to and reached towards the target
      faster than novices, whereas the estimated video cue timings for the skilled
      players were not different from those for the novices. The results suggest that
      the anticipation of attacker's direction in this task would be a general visuo
      motor skill, even without previous specialised perceptual training. Combined with
      the results from the reaction performance in the video task, we conclude that
      novices are afforded shorter times and more uncertain information before their
      stepping when they are in a one-on-one ballgame defensive scenario because their
      sidestepping takes a relatively long time.

PMID- 23534909
TI  - Reversibly thermoswitchable two-dimensional periodic gratings prepared from
      tethered poly(N-isopropylacrylamide) on silicon surfaces.
AB  - In this study we used atom transfer radical polymerization to graft poly(N
      isopropylacrylamide) (PNIPAAm) onto flat Si substrates. We then applied very
      large-scale integration and reactive ion etching sequentially to generate 200-nm
      scale hole arrays of tethered PNIPAAm as two-dimensional periodic concave
      gratings (2DPCGs) on the Si surfaces. The hole array structures of tethered
      PNIPAAm could be created and erased reversibly at 25 and 40  degrees C,
      respectively, leading to significant changes in the effective refractive index
      (neff). The values of neff of the 2DPCGs were related to the depth of their holes
      generated after etching for various times, resulting in a color change from blue
      to red that could be observed by the naked eye at incident angles of 10-20
      degrees . Moreover, we used effective-medium theory to calculate the filling
      factors of air inside the 2DPCGs to verify the structural changes of the tethered
      PNIPAAm. Such designed 2DPCGs of thermorespective hydrogel films have potential
      applications in temperature-responsive optical devices [e.g., as antireflection
      structured surfaces (ARSs)] that operate at both visible and near-infrared
      wavelengths.

PMID- 23534910
TI  - Predicting metabolic syndrome by using hematogram models in elderly women.
AB  - BACKGROUND: Low-grade inflammatory status was thought to be a major underlying
      mechanism in MetS. White blood cell (WBC) count was one of the inflammatory
      markers identified to be associated with MetS. Moreover, not only WBC but also
      hemoglobin (Hb) and platelet (PLT) were all associated with MetS. OBJECTIVE: In
      this study, we tried to build models by the hematogram components. In this way,
      we can not only predict the occurrence of MetS with a relatively low-cost and
      routine lab test, but also can understand more about the relationships between
      low grade inflammation and MetS. METHODS: We randomly collected subjects over 65
      years old from MJ Health Screening Center's database between 1999 and 2008. After
      excluding subjects with medications for hypertension, hyperlipidemia and/or
      diabetes, 13,132 female were eligible for analysis. RESULTS: All the MetS
      components, hematogram parameters and age were higher in group with MetS. In the
      correlation matrix, all these three hematogram parameters (WBC, Hb and PLT) were
      correlated with MetS components except for the correlation between Hb and HDL-C.
      The ROC curves showed that the model 3 (PLT + Hb + WBC) had greatest area under
      the curve of 0.631 with the sensitivity of 58.1% and specificity of 61.4%.
      CONCLUSIONS: Our findings have shown that all the three hematogram parameters are
      related to MetS. The results not only shed light on the complex relationships,
      but also demonstrate a common and easy model to aid clinicians to be more aware
      of the occurrence of MetS.

PMID- 23534911
TI  - A direct and quantitative three-dimensional reconstruction of the internal
      structure of disordered mesoporous carbon with tailored pore size.
AB  - A new technique that allows direct three-dimensional (3D) investigations of
      mesopores in carbon materials and quantitative characterization of their physical
      properties is reported. Focused ion beam nanotomography (FIB-nt) is performed by
      a serial sectioning procedure with a dual beam FIB-scanning electron microscopy
      instrument. Mesoporous carbons (MPCs) with tailored mesopore size are produced by
      carbonization of resorcinol-formaldehyde gels in the presence of a cationic
      surfactant as a pore stabilizer. A visual 3D morphology representation of
      disordered porous carbon is shown. Pore size distribution of MPCs is determined
      by the FIB-nt technique and nitrogen sorption isotherm methods to compare both
      results. The obtained MPCs exhibit pore sizes of 4.7, 7.2, and 18.3 nm, and a
      specific surface area of ca. 560 m(2)/g.

PMID- 23534912
TI  - How aware are migraineurs of their triggers?
AB  - BACKGROUND: Broad discrepancies in the number of migraine triggers have been
      reported in several studies. Migraineurs do not seem to recognize easily headache
      triggers in clinical practice. OBJECTIVE: To evaluate how aware migraineurs are
      about their headache triggers. MATERIALS AND METHODS: We recruited 120
      consecutive migraineurs. Each patient was first asked to report spontaneously any
      migraine trigger. Subsequently, the patient selected from a list of commonly
      known triggers. RESULTS: Ninety-seven patients (72.5%) spontaneously reported at
      least 1 migraine trigger, and 120 patients (100%) reported at least 1 migraine
      trigger selecting from a specific list of precipitants. The mean number of
      spontaneously identified triggers was 1.5 (+/-1.5), and the total number of
      triggers identified was 7.20 (+/-3.9). CONCLUSIONS: A relevant discrepancy
      between the number of spontaneously recognized triggers and the total number of
      triggers was found. This may suggest that migraineurs display poor awareness
      about headache triggers.

PMID- 23534913
TI  - Microwave-induced plasma desorption/ionization source for ambient mass
      spectrometry.
AB  - A new ionization source based on microwave induced plasma was developed for
      ambient desorption/ionization. The microwave-induced plasma desorption/ionization
      source (MIPDI) was composed of a copper Surfatron microwave cavity where a fused
      silica tube was centered axially. Stable nonlocal thermodynamic equilibrium
      plasma was generated in the quartz discharge tube when a microwave at a frequency
      of 2450 MHz was coupled to the microwave cavity. Analytes deposited on the
      surface of poly(tetrafluoroethylene) (PTFE) or quartz slide after hydrofluoric
      acid (HF) etching were desorbed and ionized by the plasma. The performance of the
      MIPDI technique was validated by the analysis of a variety of chemical
      substances, polymer compounds, and pharmaceutical drugs using argon or helium as
      the discharge gas. Protonated [M + H](+) or deprotonated [M - H](-) ions were
      observed in the positive or negative mode. MIPDI was also used for the analysis
      of compounds in a complex matrix without any sample preparation. MIPDI was also
      capable of analyzing liquid samples. The signal-to-noise ratio was 463 in the
      analysis of 9.2 ng of phenylalanine, and the limit of detection was 60 pg for
      phenylalanine. MIPDI could desorb and ionize analytes with a molecular weight of
      up to 1200, which was demonstrated by the analysis of polyethylene glycol 800
      (PEG800). MIPDI has advantages of simple instrumentation, relatively high
      temperature, stability, and reproducibility. 

PMID- 23534914
TI  - Distribution and factors associated with four premature ejaculation syndromes in
      outpatients complaining of ejaculating prematurely.
AB  - INTRODUCTION: Because available definitions of premature ejaculation (PE) were
      unable to encompass the various forms of PE, Waldinger et al. proposed a new
      classification that distinguished four PE syndromes. However, few studies have
      examined the prevalence rates of these four PE syndromes. AIMS: The study aims to
      analyze the prevalence of and factors associated with four PE syndromes in
      outpatients who complained of ejaculating prematurely. METHODS: Between December
      2009 and December 2011, outpatients who complained of PE completed a detailed
      verbal questionnaire regarding their demographic data and medical and sexual
      history. Each patient was classified as having one of four PE subtypes: lifelong
      PE (LPE), acquired PE (APE), natural variable PE (NVPE), or premature-like
      ejaculatory dysfunction (PLED). MAIN OUTCOME MEASURES: Based on the new
      classification scheme, PE was classified into four subtypes. The
      anxiety/depression status of patients was assessed by the Zung self-rating
      anxiety/depression scales, and erectile function was assessed by the
      International Index of Erectile Function-5 instrument. RESULTS: This study
      included 1,988 male outpatients who complained of PE, with mean ages and body
      mass index (BMI) scores of 35.52 +/- 10.38 years and 25.34 +/- 4.51 kg/m(2),
      respectively. Prevalence rates of PE syndromes were 35.66% for LPE, 28.07% for
      APE, 12.73% for NVPE, and 23.54% for PLED. Patients with APE had the highest mean
      ages and BMI scores, and they more frequently reported several comorbidities,
      including sexual desire disorder, hypertension, diabetes mellitus, chronic
      prostatitis, and erectile dysfunction. The PLED group had a lower mean frequency
      of sexual intercourse than other groups and higher rates of anxiety and
      depression. CONCLUSION: The prevalence of LPE was higher than that of other PE
      subtypes in an outpatient setting. Several comorbidities were more common in
      patients with APE and PLED. In particular, a lower frequency of intercourse and
      higher frequencies of anxiety and depression were found in patients with PLED.

PMID- 23534915
TI  - Early healing of the alveolar process after tooth extraction: an experimental
      study in the beagle dog.
AB  - AIM: To describe the early healing events in the alveolar socket during the first
      8 weeks of spontaneous healing after tooth extraction. MATERIALS AND METHODS: 16
      adult beagle dogs were selected and five healing periods were analysed (4 h, 1
      week, 2 weeks, 4 weeks, 8 weeks). Mandibular premolars were extracted and each
      socket corresponding to the mesial root was left to heal undisturbed. In each
      healing period, three animals were euthanatized, each providing four study sites.
      Healing was assessed by descriptive histology and by histometric analysis using
      as landmarks: the vertical distance between buccal and lingual crest (B'L') and
      the width of buccal and lingual walls at three different levels. Differences
      between means for each variable for each healing period were compared (ANOVA; p <
      0.05). RESULTS: B'L' at baseline was 0.45 (0.18) mm and decreased during the
      healing period to a final value of 0.18 (0.08) mm. The lingual width (Lw) remains
      almost unchanged while the buccal width (Bw) at 1 (Bw1) and 2 (Bw2) mm was
      reduced in about 40% of its initial value. CONCLUSIONS: Minor vertical bone
      reduction in both the buccal and lingual socket walls were observed. A marked
      horizontal reduction of the buccal bone wall was observed mostly in its coronal
      aspect.

PMID- 23534916
TI  - Can genetics aggravate the health of isolated and remote populations? The case of
      gout, hyperuricaemia and osteoarthritis in Dalmatia.
AB  - INTRODUCTION: The aim of this study was to investigate whether genetics may be
      considered an additional risk factor for health in isolated and remote
      populations, compared with their populations of origin. In this study, two remote
      island population samples from Croatia (from the islands of Vis and the Korcula)
      were compared with mainland controls from the coastal city of Split. The analyses
      focused on gout, hyperuricaemia and osteoarthritis, as examples of complex,
      multifactorial diseases. METHODS: A total of 3006 examinees from all three sites
      in Dalmatia, Croatia were included in the descriptive part of the study, within a
      large-scale project of 10,001 Dalmatians. Additionally, a subset of 2428 subjects
      was genotyped and information on three genomic loci was used in this study. All
      three loci belong to SLC2A9 gene, considered to have a major role in the
      regulation of serum uric acid concentration (rs6449213, rs1014290 and rs737267).
      RESULTS: There was a much a higher prevalence of gout in the isolated populations
      compared with the mainland sample (3.3% in Vis, 2.2% in Korcula and 1.7% in
      Split, after age standardization). Furthermore, standardized prevalence of
      hyperuricaemia (defined as serum uric acid >=403 mmol/L) was 9.9% in Vis, 5.6% in
      Korcula and 6.1% in Split. Analysis of the allele frequencies for the three loci
      of SLC2A9 suggested that in all three instances the prevalence of deleterious
      genotypes was highest in Vis, followed by Korcula, which had higher or comparable
      prevalence to the city of Split. Multivariate analysis, adjusted for the main
      confounder effects indicated that those on the island of Vis, which has the
      higher degree of isolation, had significantly higher odds ratio for both
      hyperuricaemia (odds ratio 1.90 95% confidence intervals [1.36-2.64]) and
      osteoarthritis, but not gout (3.37 [2.14-5.32]). The difference between Split and
      Korcula included only greater odds for osteoarthritis (1.92 [1.20-3.06]).
      CONCLUSIONS: Isolated and remote populations that maintain a sufficient level of
      genetic isolation may suffer not only from consequences of geographic and social
      isolation, but their population genetic structure may also further contribute to
      poorer health status and outcomes.

PMID- 23534917
TI  - Effective Henry's law partitioning and the salting constant of glyoxal in
      aerosols containing sulfate.
AB  - The reversible partitioning of glyoxal was studied in simulation chamber
      experiments for the first time by time-resolved measurements of gas-phase and
      particle-phase concentrations in sulfate-containing aerosols. Two complementary
      methods for the measurement of glyoxal particle-phase concentrations are
      compared: (1) an offline method utilizing filter sampling of chamber aerosols
      followed by HPLC-MS/MS analysis and (2) positive matrix factorization (PMF)
      analysis of aerosol mass spectrometer (AMS) data. Ammonium sulfate (AS) and
      internally mixed ammonium sulfate/fulvic acid (AS/FA) seed aerosols both show an
      exponential increase of effective Henry's law coefficients (KH,eff) with AS
      concentration (cAS, in mol kg(-1) aerosol liquid water, m = molality) and sulfate
      ionic strength, I(SO4(2-)) (m). A modified Setschenow plot confirmed that
      "salting-in" of glyoxal is responsible for the increased partitioning. The
      salting constant for glyoxal in AS is K(S)CHOCHO = (-0.24 +/- 0.02) m(-1), and
      found to be independent of the presence of FA. The reversible glyoxal uptake can
      be described by two distinct reservoirs for monomers and higher molecular weight
      species filling up at characteristic time constants. These time constants are
      tau1 ~ 10(2) s and tau2 ~ 10(4) s at cAS < 12 m, and about 1-2 orders of
      magnitude slower at higher cAS, suggesting that glyoxal uptake is kinetically
      limited at high salt concentrations.

PMID- 23534918
TI  - Orbital metastases as the primary presentation of lobular breast cancer.

PMID- 23534920
TI  - Coronary artery calcification score and carotid intima media thickness in
      patients with von Willebrand disease.

PMID- 23534921
TI  - Analysis of aromaticity in planar metal systems using the linear response kernel.
AB  - The linear response kernel is used to gain insight into the aromatic behavior of
      the less classical metal aromatic E4(2-) and CE4(2-) (E = Al, Ga) clusters. The
      effect of the systematic replacement of the aluminum atoms in Al4(2-) and CAl4(2
      ) by germanium atoms is studied using, Al3Ge-, Al2Ge2, AlGe3+, Ge4(2+), CAl3Ge-,
      CAl2Ge2, CAlGe3+, and CGe4(2+). The results are compared with the values of the
      delocalization index (delta(1,3)) and nucleus independent chemical shifts
      (NICS(zz)). Unintegrated plots of the linear response, computed for the first
      time on molecules, are used to analyze the delocalization in these clusters. All
      aromaticity indices studied, the linear response, delta(1,3), and NICS(zz),
      predict that the systems with a central carbon are less aromatic than the systems
      without a central carbon atom. Also, the linear response is more pronounced in
      the sigma-electron density than in the pi-density, pointing out that the systems
      are mainly sigma-aromatic.

PMID- 23534919
TI  - Polymeric curcumin nanoparticle pharmacokinetics and metabolism in bile duct
      cannulated rats.
AB  - The objective of this study was to compare the pharmacokinetics and metabolism of
      polymeric nanoparticle-encapsulated (nanocurcumin) and solvent-solubilized
      curcumin formulations in Sprague-Dawley (SD) rats. Nanocurcumin is currently
      under development for cancer therapy. Since free, unencapsulated curcumin is
      rapidly metabolized and excreted in rats, upon intravenous (i.v.) administration
      of nanocurcumin only nanoparticle-encapsulated curcumin can be detected in plasma
      samples. Hence, the second objective of this study was to utilize the metabolic
      instability of curcumin to assess in vivo drug release from nanocurcumin.
      Nanocurcumin and solvent-solubilized curcumin were administered at 10 mg
      curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5).
      Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the
      solvent-solubilized curcumin. Nanocurcumin also increased the relative abundance
      of curcumin and glucuronides in bile but did not dramatically alter urine and
      tissue metabolite profiles. The observed increase in biliary and urinary
      excretion of both curcumin and metabolites for the nanocurcumin formulation
      suggested a rapid "burst" release of curcumin. Although the burst release
      observed in this study is a limitation for targeted tumor delivery, nanocurcumin
      still exhibits major advantages over solvent-solubilized curcumin, as the
      nanoformulation does not result in the lung accumulation observed for the solvent
      solubilized curcumin and increases overall systemic curcumin exposure.
      Additionally, the remaining encapsulated curcumin fraction following burst
      release is available for tumor delivery via the enhanced permeation and retention
      effect commonly observed for nanoparticle formulations.

PMID- 23534922
TI  - Successful treatment of congenital melanocytic nevus on tragus with CO2 laser.
AB  - BACKGROUND: Congenital melanocytic nevus (CMN) has an increasing risk of
      malignancy and may cause cosmetic and psychological problems. Surgery has been
      the main therapy for most cases. However, it is often not suitable for all
      lesions. Treatment of these lesions can be challenging to plastic surgeons. CO2
      laser, with the special function, is another effective treatment for some CMN.
      METHODS: Both lesions were treated with a short-pulsed CO2 laser in conjunction
      with a local anesthetic; the superfluous tissue was pruned and ablated to get a
      crude tragus and then carefully shaped to form an aesthetically tragus. RESULTS:
      Showed good cosmetic results without pigment recurrence and scar formation 1 year
      after operation in both patients, the exception being a small area of cartilage
      that was covered with epithelial tissues on the surface in patient 1.
      CONCLUSIONS: CO2 laser treatment is a useful modality in treating some CMN that
      are located on sites deemed inoperable. It can help to shape the lesions into
      their original form with the advantage of hemostasis and tissue manipulation
      proving to be effective, thus avoiding suturing and skin grafting. Taking the
      thermal damage into account can help to minimize the side effects and attain a
      desirable cosmetic outcome.

PMID- 23534924
TI  - Augmenting second harmonic generation using Fano resonances in plasmonic systems.
AB  - Significant augmentation of second harmonic generation using Fano resonances in
      plasmonic heptamers made of silver is theoretically and experimentally
      demonstrated. The geometry is engineered to simultaneously produce a Fano
      resonance at the fundamental wavelength, resulting in a strong localization of
      the fundamental field close to the system, and a higher order scattering peak at
      the second harmonic wavelength. These results illustrate the versatility of Fano
      resonant structures to engineer specific optical responses both in the linear and
      nonlinear regimes thus paving the way for future investigations on the role of
      dark modes in nonlinear and quantum optics.

PMID- 23534923
TI  - Development of cortical influences on superior colliculus multisensory neurons:
      effects of dark-rearing.
AB  - Rearing cats from birth to adulthood in darkness prevents neurons in the superior
      colliculus (SC) from developing the capability to integrate visual and non-visual
      (e.g. visual-auditory) inputs. Presumably, this developmental anomaly is due to a
      lack of experience with the combination of those cues, which is essential to form
      associative links between them. The visual-auditory multisensory integration
      capacity of SC neurons has also been shown to depend on the functional integrity
      of converging visual and auditory inputs from the ipsilateral association cortex.
      Disrupting these cortico-collicular projections at any stage of life results in a
      pattern of outcomes similar to those found after dark-rearing; SC neurons respond
      to stimuli in both sensory modalities, but cannot integrate the information they
      provide. Thus, it is possible that dark-rearing compromises the development of
      these descending tecto-petal connections and the essential influences they
      convey. However, the results of the present experiments, using cortical
      deactivation to assess the presence of cortico-collicular influences, demonstrate
      that dark-rearing does not prevent the association cortex from developing robust
      influences over SC multisensory responses. In fact, dark-rearing may increase
      their potency over that observed in normally-reared animals. Nevertheless, their
      influences are still insufficient to support SC multisensory integration. It
      appears that cross-modal experience shapes the cortical influence to selectively
      enhance responses to cross-modal stimulus combinations that are likely to be
      derived from the same event. In the absence of this experience, the cortex
      develops an indiscriminate excitatory influence over its multisensory SC target
      neurons.

PMID- 23534925
TI  - Elder abuse through a life course lens.
AB  - BACKGROUND: This paper provides the findings from a large pilot study, Defining
      and Measuring Elder Abuse and Neglect, a precursor to a national prevalence study
      to be conducted in Canada beginning in September 2013. One purpose of this study
      and the focus of this paper was to determine whether a life course perspective
      would provide a useful framework for examining elder abuse. The two-year pilot
      study, 2009-2011, examined the prevalence of perceptions of abuse at each life
      stage by type of abuse, the importance of early life stage abuse in predicting
      types of elder abuse, and early life stage abuse as a risk factor for elder
      abuse. METHODS: Older adults who were aged >=55 years (N = 267) completed a cross
      sectional telephone survey, comprising measures of five types of elder abuse
      (neglect, physical, sexual, psychological, and financial) and their occurrence
      across the life course: childhood (<=17 years), young adulthood (18 to 24 years),
      and older adulthood (5 to 12 months prior to the interview date). Data analyses
      included descriptive statistics, bivariate correlations for abuse at the various
      life stages, and the estimation of logistic regression models that examined
      predictors of late life abuse, and multinomial logistic regression models
      predicting the frequency of abuse. RESULTS: Fifty-five percent of the sample
      reported abuse during childhood, and 34.1% reported abuse during young adulthood.
      Forty-three percent said they were abused during mature adulthood, and 24.4% said
      they were abused since age 55 but prior to the interview date of the study.
      Psychological (42.3%), physical (26.6%), and sexual abuses (32.2%) were the most
      common abuses in childhood while psychological abuse was the most common type of
      abuse at each life stage. When the risk factors for abuse were considered
      simultaneously including abuse during all three life stages, only a history of
      abuse during childhood retained its importance (OR = 1.81, p = 0.046, CI = 1.01
      3.26). Abuse in childhood increased the risk of experiencing one type of abuse
      relative to no abuse, but was also unrelated to experiencing two or more types of
      abuse compared to no abuse. CONCLUSIONS: Results suggest that a life course
      perspective provides a useful framework for understanding elder abuse and
      neglect. The findings indicate that a childhood history of abuse in this sample
      had a deciding influence on later mistreatment, over and above what happens later
      in life.

PMID- 23534926
TI  - Elf5 - breast cancer's little helper.
AB  - A variety of transcription factors has been shown to regulate lineage commitment
      in the mammary gland and to be associated with different molecular subtypes of
      breast cancer. E74-like factor 5 (Elf5) has now been identified as a marker of
      oestrogen receptor status, and high expression correlates with more aggressive
      basal cancers and resistance to anti-oestrogens. Manipulation of Elf5 transcript
      levels perturbs the molecular profiles of luminal and basal subtypes,
      highlighting the possibility that targeting Elf5 could provide a new approach for
      the treatment of basal cancers. 

PMID- 23534927
TI  - Fat-resident Tregs: an emerging guard protecting from obesity-associated
      metabolic disorders.
AB  - Obesity, a chronic, low-grade inflammatory disease, is associated with
      alterations of multiple immune-cell components in the visceral adipose tissue
      (VAT), in which CD4(+) Foxp3(+) regulatory T cells (Tregs) have been suggested to
      be a critical regulator. This review focuses on the current understanding of VAT
      resident Tregs (VAT Tregs) and their intriguing roles in modulating fat tissue
      inflammation and obesity-associated metabolic disorders. The potential mechanisms
      for the regulation of VAT Tregs in lean vs. obese individuals are also discussed.
      Accumulating evidence reveals that the modulation of VAT Tregs may offer a
      potential novel strategy for treating obesity-related metabolic disorders, such
      as insulin resistance and type 2 diabetes.

PMID- 23534928
TI  - Susceptibility of methicillin-resistant Staphylococci clinical isolates to
      netilmicin and other antibiotics commonly used in ophthalmic therapy.
AB  - PURPOSE: The aim of this study was to test the activity of selected antimicrobial
      agents commonly used in the treatment of ocular infections against methicillin
      resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus
      epidermidis (MRSE) isolates. METHODS: A total of 43 staphylococci from
      respiratory tract and ocular infections were characterized for methicillin
      resistance using the Epsilometer test (E-test), the polymerase chain reaction for
      mecA gene detection and the PBP2' latex agglutination test. A perfect agreement
      among them was observed in 20 isolates (8 MRSA and 12 MRSE) which were then
      employed in the susceptibility test by using the agar disk diffusion test
      (NCCLS). The antibiotics tested were: netilmicin (NET), tobramycin (TOB),
      azithromycin (AZM), levofloxacin (LEV), moxifloxacin (MXF), chloramphenicol (C)
      and vancomycin (VA). RESULTS: All MRSE and most (87.5%) of MRSA isolates tested
      were NET and VA sensitive. The majority of MRSA were found to be resistant to all
      the other antibiotics, with the exception of C. In particular, 75%, 87% and 100%
      of the isolates were resistant to fluoroquinolones (LEV and MXF), AZM and TOB,
      respectively. As for the MRSE group, 25% of the strains tested were resistant to
      C and MXF while 33%, 42% and 58% of the strains were resistant to LEV, AZM and
      TOB, respectively. CONCLUSIONS: Together with VA, NET was the most effective
      antibiotic tested against both MRSA and MRSE clinical isolates. The exclusive
      topical use of NET for the treatment of ocular infections may curtail the
      emergence, spreading and persistence of antibiotic-resistant bacteria.

PMID- 23534929
TI  - Artificial photosynthetic reaction center with a coumarin-based antenna system.
AB  - In photosynthesis, sunlight is absorbed mainly by antenna chromophores that
      transfer singlet excitation energy to reaction centers for conversion to useful
      electrochemical energy. Antennas may likewise be useful in artificial
      photosynthetic systems that use sunlight to make fuels or electricity. Here, we
      report the synthesis and spectroscopic properties of a molecular hexad comprising
      two porphyrin moieties and four coumarin antenna chromophores, all organized by a
      central hexaphenylbenzene core. Light absorbed by any of the coumarins is
      transferred to a porphyrin on the 1-10 ps time scale, depending on the site of
      initial excitation. The quantum yield of singlet energy transfer is 1.0. The
      energy transfer rate constants are consistent with transfer by the Forster dipole
      dipole mechanism. A pyridyl-bearing fullerene moiety self-assembles to the form
      of the hexad containing zinc porphyrins to yield an antenna-reaction center
      complex. In the resulting heptad, energy transfer to the porphyrins is followed
      by photoinduced electron transfer to the fullerene with a time constant of 3 ps.
      The resulting P(*+)-C60(*-) charge-separated state is formed with an overall
      quantum yield of 1.0 and decays with a time constant of 230 ps in 1,2
      difluorobenzene as the solvent. 

PMID- 23534930
TI  - Antileishmanial activity evaluation of bis-lawsone analogs and DNA topoisomerase
      I inhibition studies.
AB  - For the development of potent novel antileishmanial agents, 3,3'
      (arylmethylene)bis(2-hydroxynaphthalene-1,4 dione) derivatives were synthesized
      from lawsone and evaluated for cytotoxicity on Leishmania donovani promastigotes
      as well as on leishmanial DNA topoisomerase-I. Enzyme inhibition studies were
      conducted with simultaneous and preincubation conditions. Total inhibition is
      compared to camptothecin (CPT), which was taken as positive control on both the
      systems of enzyme inhibition. The range of activity varied from 37.5 to 70 uM in
      simultaneous assay and 13-16 uM in preincubation assay. Furthermore, when
      evaluated against L. donovani promastigotes, the synthesized compounds exhibited
      the activity ranging from 2 to 14 uM. The results revealed that all the compounds
      exhibit promising antileishmanial activity.

PMID- 23534931
TI  - Discovery of a series of small molecules as potent histone deacetylase
      inhibitors.
AB  - A series of small molecules were designed and synthesized based on our previous
      virtual screening approach, which was performed to discover potent histone
      deacetylase inhibitors (HDACIs) with novel structures. The derived compounds were
      tested by Hela cell nucleus extract for enzyme inhibition assay. Tumor cell
      growth inhibition assays were performed using a series of tumor cell lines.
      Molecule 4h has the best performance among these compounds with enzyme inhibition
      IC50 of 0.14 MUM and tumor cell growth inhibition IC50 of 1.85 (U937), 2.02
      (HL60), 2.67 (K562). Docking studies showed that multiple H-bonds and hydrophobic
      interactions make 4h binding to the active site of HDAC. 4h has the advantage of
      low molecular weight, so a variety of structural modifications can be performed
      in our further studies.

PMID- 23534932
TI  - Discovery of Entamoeba histolytica hexokinase 1 inhibitors through homology
      modeling and virtual screening.
AB  - Entamoeba histolytica, the parasite which causes amebiasis is responsible for
      110,000 deaths a year. Entamoeba histolytica depends on glycolysis to obtain ATP
      for cellular work. According to metabolic flux studies, hexokinase exerts the
      highest flux control of this metabolic pathway; therefore, it is an excellent
      target in the search of new antiamebic drugs. To this end, a tridimensional model
      of E. histolytica hexokinase 1 (EhHK1) was constructed and validated by homology
      modeling. After virtual screening of 14,400 small molecules, the 100 with the
      best docking scores were selected, purchased and assessed in their inhibitory
      capacity. The results showed that three molecules (compounds 2921, 11275 and
      2755) inhibited EhHK1 with an I50 of 48, 91 and 96 uM, respectively. Thus, we
      found the first inhibitors of EhHK1 that can be used in the search of new
      chemotherapeutic agents against amebiasis.

PMID- 23534933
TI  - Color and chemical stability of a variety of anthocyanins and ascorbic acid in
      solution and powder forms.
AB  - The color and chemical stabilities of six anthocyanins, including cyanidin 3
      glucoside, highly purified and present in semipurified extracts (also containing
      other anthocyanins) from grape pomace, purple corn, and black rice, were
      determined in combination with ascorbic acid in solutions at differing pH values
      (3.0 and 4.0) and temperatures (6-40  degrees C) and lyophilized powders at
      different relative humidities (43-98% RH). Color and chemical changes were
      analyzed using CIELAB measurements and HPLC, respectively. In liquids, stability
      was inversely related to increasing pH and temperature; for powders, stability
      was inversely related to RH. The mutual destruction of anthocyanins and ascorbic
      acid in solution was confirmed, with unexpected new findings showing no
      significant stabilizing/destabilizing effect based upon anthocyanin structure,
      including differing flavylium core (three types) and type of acylation (two
      aliphatic, one cinnamic acid), or final extract purity. 

PMID- 23534934
TI  - Diagnostic value of the skin lesions in immune dysregulation, polyendocrinopathy,
      enteropathy, X-linked syndrome.
AB  - We report a child with immune dysregulation, polyendocrinopathy, enteropathy, X
      linked (IPEX) syndrome due to a de novo c.1190G>A (p.R397Q) mutation in exon 11
      of the forkhead domain of the FOXP3 gene. He had chronic dermatitis with an
      eczematous and ichthyosiform appearance and had an allogeneic bone marrow
      transplantation. IPEX syndrome is a rare, often fatal recessive disease caused by
      mutations in the FOXP3 gene on the X chromosome (Xp11.23-q13.3). 

PMID- 23534935
TI  - An uncommon cause of headache resolution: spontaneous ventriculostomy in
      obstructive hydrocephalus.

PMID- 23534936
TI  - Therapeutic angiogenesis for the critical limb ischemia decreases platelet
      activation.
AB  - Platelets are required for the recruitment of bone marrow-derived mononuclear
      cells (BMMNC) into ischemia-induced vasculature, which underlines their key role
      in angiogenesis. The difference in platelet immunophenotype between healthy
      controls and patients with critical limb ischemia (CLI) treated with therapeutic
      angiogenesis (TA) using BMMNC was assessed. The impact of TA on the expression of
      platelet membrane markers was studied as well. CLI patients (N = 26) and blood
      donors as controls (N = 21) were enrolled. Bone marrow (600 +/- 50 ml) was
      centrifuged (3200 g, 20 min, 22  degrees C). BMMNC (100-120 ml) were separated by
      Optipress I and implanted to the ischemic limb using deep intramuscular
      injections. Flow cytometry was employed for the peripheral blood platelets
      immunophenotyping. CD41FITC, CD62PE, CD36FITC, CD29FITC antibodies were used.
      Patients were followed up prior to the procedure and at months 1, 3 and 6. The
      expression of CD41 was lower in CLI patients than in the controls. P-selectin
      (CD62P) was higher in CLI patients than in controls at the baseline and at month
      6. It was significantly down-regulated at month 3, however not at months 1 and 6
      compared to baseline. Platelet GPIV (CD36) was higher at the baseline, but not
      during the follow-up compared to the controls. beta1-integrin (CD29)
      progressively decreased during the follow-up as compared to the baseline value.
      Platelets in CLI express P-selectin, GPIV and beta1-integrin more abundantly than
      platelets of healthy subjects. TA down-regulates the expression of the respective
      markers. Possible mechanism could be higher clearance of the activated platelets
      in the ischemic tissues during angiogenesis.

PMID- 23534937
TI  - Sexual functioning in women with mild and severe symptoms of Charcot-Marie-Tooth
      disease.
AB  - INTRODUCTION: Charcot-Marie-Tooth (CMT) disease is one of the most frequently
      inherited neurological disorders, and while it is known that individuals
      suffering from this condition have low quality of life, little is known about
      their sexual function and satisfaction. AIM: To describe the functioning on
      different domains of sexuality in a relatively large sample of women with CMT,
      provide comparisons between mildly and severely affected patients and between
      women with the two different types of CMT (demyelinating vs. axonal), and assess
      the relationship between sexual function and age of onset. METHODS: Fifty-seven
      women (age: 18-60 years) were approached in a CMT rehabilitation clinic by a
      psychologist and administered the Italian version of the McCoy Female Sexuality
      Questionnaire (MFSQ). Data from 40 patients who had had sexual intercourse in the
      previous 4 weeks were analyzed. MAIN OUTCOME MEASURE: The main outcome measures
      are the factors MFSQ-SEX and MFSQ-PARTNER, which describe sexual functioning and
      sexual satisfaction with a partner, respectively. RESULTS: Almost 30% of women
      did not engage in sexual intercourse with a partner. Overall sexual problems were
      more prominent in younger women and tended to be lower as age increased: this
      pattern was different from what was reported in previous studies in comparable
      samples of healthy Italian women. Severity of CMT was associated with better
      sexual functioning in the areas of desire, arousal, orgasm, and satisfaction,
      with women with more severe symptoms reporting greater functioning. Women with
      more severe CMT symptoms reported more pain during intercourse. Age of CMT onset
      and type of CMT (demyelinating vs. axonal) were not associated with differences
      in sexual functioning. CONCLUSIONS: Findings point to the importance of including
      assessment of sexual dysfunction in young women with mild CMT symptoms and the
      importance of providing sex therapy or counseling to these patients.

PMID- 23534938
TI  - Unusual DNA structures formed on bare highly oriented pyrolytic graphite surfaces
      studied by atomic force microscopy.
AB  - It is important to know the detailed DNA structure on carbonaceous surfaces for
      further application of DNA-functionalized carbonaceous materials in diverse
      research areas. In this study, the topographic and structural characteristics of
      the separated single DNA molecules and their assembly on highly oriented
      pyrolytic graphite (HOPG) surfaces have been investigated by atomic force
      microscopy (AFM). AFM results indicate that both circular and linear DNA
      molecules tend to form hexagonal patterns along with some unusual structures that
      include node, protrusion, cruciform, parallel single-stranded DNA (ssDNA), and
      compact zigzag. Furthermore, parallel ssDNA patterns and their crossed structures
      have been obtained under high-temperature conditions. Our AFM results reveal that
      a bare HOPG surface can induce DNA molecules to form various unusual structures.
      This finding is helpful for understanding the adsorption behavior of DNA on other
      carbonaceous surfaces such as carbon nanotubes and graphene. In addition, the
      hexagonal DNA patterns in this study are similar to those formed on the
      alkylamine-modified HOPG surface, which implies that a bare HOPG, without any
      chemical modification, has a strong ability to align biomolecules. This study
      could expand our knowledge of the diversities of DNA structures and the aligning
      ability of carbonaceous surfaces.

PMID- 23534940
TI  - Increased bone loss and amount of osteoclasts in kinin B1 receptor knockout mice.
AB  - AIM: The pathophysiology of periodontal diseases involves aspects of immunity and
      bone remodelling. Considering the role of the kinin B1 receptor (Bdkrb1) in
      inflammation and healing, the purpose of this study was to evaluate the
      contribution of Bdkrb1 to the pathogenesis of periodontitis. MATERIAL AND
      METHODS: We used a model of ligature-induced experimental periodontitis (LIEP) in
      mice lacking Bdkrb1 (Bdkrb1(-/-) ) to test the role of this receptor in bone loss
      and cytokine secretion by lymph nodes cells. Angiotensin-converting enzyme
      inhibitor (ACEi) was used as a pharmacological strategy to support the genetic
      model. Also, autonomous effect of Bdkrb1 deletion was evaluated in osteoclasts
      precursors from bone marrow. RESULTS: Bdkrb1(-/-) mice exhibit increased bone
      loss and IL-17 secretion in response to LIEP when compared to wild type. LIEP
      does not modify TNF-alpha, IFN-gamma and IL-10 levels in Bdkrb1(-/-) mice after
      21 days. Bone marrow cells from Bdkrb1(-/-) displayed increased differentiation
      into functional osteoclasts with consistent artificial calcium phosphate
      degradation. Furthermore, treatment of mice with ACEi prevented bone destruction.
      CONCLUSION: Bdkrb1 participates in the pathogenesis of LIEP bone loss possibly
      through mechanisms that involve modulation of the TH 17 response, thereby
      demonstrating its role in the development of periodontitis.

PMID- 23534941
TI  - Bioinspired synthesis of a soft-nanofilament-based coating consisting of
      polysilsesquioxanes/polyamine and its divergent surface control.
AB  - The synthesis of polysilsesquioxanes coating with controllable one-dimensional
      nanostructure on substrates remains a major long-term challenge by conventional
      solution-phase method. The hydrolytic polycondensation of organosilanes in
      solution normally produces a mixture of incomplete cages, ladderlike, and network
      structures, resulting in the poor control of the formation of specific
      nanostructure. This paper describes a simple aqueous process to synthesize
      nanofilament-based coatings of polysilsesquioxanes possessing various organo
      functional groups (for example, thiol, methyl, phenyl, vinyl, and epoxy). We
      utilized a self-assembled nanostructured polyamine layer as a biomimetically
      catalytic scaffold/template to direct the formation of one-dimensional
      nanofilament of polysilsesquioxanes by temporally and spatially controlled
      hydrolytic polycondensation of organosilane. The surface nanostructure and
      morphology of polysilsesquioxane coating could be modulated by changing
      hydrolysis and condensation reaction conditions, and the orientation of
      nanofilaments of polysilsesquioxanes on substrates could be controlled by simply
      adjusting the self-assembly conditions of polyamine layer. The nanostructure and
      polyamine@polysilsesquioxane hybrid composition of nanofilament-based coatings
      were examined by means of scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The
      template role of nanostructured polyamine layer for the formation of
      polysilsesquioxane nanofilament was confirmed by combining thin film X-ray
      diffraction (XRD) and XPS measurements. Moreover, these nanotextured coatings
      with various organo-functional groups could be changed into superhydrophobic
      surfaces after surface modification with fluorocarbon molecule.

PMID- 23534942
TI  - Oxorhenium complexes bearing the water-soluble tris(pyrazol-1
      yl)methanesulfonate, 1,3,5-triaza-7-phosphaadamantane, or related ligands, as
      catalysts for Baeyer-Villiger oxidation of ketones.
AB  - New rhenium(VII or III) complexes [ReO3(PTA)2][ReO4] (1) (PTA = 1,3,5-triaza-7
      phosphaadamantane), [ReO3(mPTA)][ReO4]I (2) (mPTA = N-methyl-1,3,5-triaza-7
      phosphaadamantane cation), [ReO3(HMT)2][ReO4] (3) (HMT = hexamethylenetetramine),
      [ReO3(eta(2)-Tpm)(PTA)][ReO4] (4) [Tpm = hydrotris(pyrazol-1-yl)methane, HC(pz)3,
      pz = pyrazolyl], [ReO3(Hpz)(HMT)][ReO4] (5) (Hpz = pyrazole), [ReO(Tpms)(HMT)]
      (6) [Tpms = tris(pyrazol-1-yl)methanesulfonate, O3SC(pz)3(-)] and
      [ReCl2{N2C(O)Ph}(PTA)3] (7) have been prepared from the Re(VII) oxide Re2O7 (1-6)
      or, in the case of 7, by ligand exchange from the benzoyldiazenido complex
      [ReCl2{N2C(O)Ph}(Hpz)(PPh3)2], and characterized by IR and NMR spectroscopies,
      elemental analysis and electrochemical properties. Theoretical calculations at
      the density functional theory (DFT) level of theory indicated that the
      coordination of PTA to both Re(III) and Re(VII) centers by the P atom is
      preferable compared to the coordination by the N atom. This is interpreted in
      terms of the Re-PTA bond energy and hard-soft acid-base theory. The oxo-rhenium
      complexes 1-6 act as selective catalysts for the Baeyer-Villiger oxidation of
      cyclic and linear ketones (e.g., 2-methylcyclohexanone, 2-methylcyclopentanone,
      cyclohexanone, cyclopentanone, cyclobutanone, and 3,3-dimethyl-2-butanone or
      pinacolone) to the corresponding lactones or esters, in the presence of aqueous
      H2O2. The effects of a variety of factors are studied toward the optimization of
      the process.

PMID- 23534943
TI  - Label-free colorimetric aptasensor based on nicking enzyme assisted signal
      amplification and DNAzyme amplification for highly sensitive detection of
      protein.
AB  - Highly sensitive detection of proteins is essential to biomedical research as
      well as clinical diagnosis. Here, we develped a novel label-free colorimetric
      aptasensor based on nicking enzyme assisted signal amplification and DNAzyme
      amplification for highly sensitive detection of protein. The system consists of a
      hairpin DNA probe carrying an aptamer sequence for target, a G-riched DNA probe
      containing two G-riched DNAzyme segments and the recognition sequence as well as
      cleavage site for nicking enzyme, a blocker DNA, and the nicking enzyme. The
      hybridization of the G-riched DNA with the blocker DNA prohibits the formation of
      the activated DNAzymes in the absence of target. Upon addition of target to the
      system, the hairpin probe is opened by the specific recognition of the target to
      its aptamer. The open hairpin probe hybridizes with a G-riched DNA and forms a
      DNA duplex, which triggers the selective cleavage of the G-riched DNA probe by
      nicking enzyme, leading to the release of the aptamer-target complex and the G
      riched DNAzyme segments. The released open hairpin probe then hybridizes with
      another G-riched DNA probe, and the cycle starts anew, resulting in the
      continuous cleavage of the G-riched DNA probes, generating a much of G-riched
      DNAzyme segments. The G-riched DNAzyme segments interact with hemin and generates
      the activated DNAzyme that can catalyze the H2O2-mediated oxidation of 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(2-)) to the colored ABTS(*-),
      thus providing the amplified colorimetric detection of target. With the use of
      thrombin (Tb) as a proof-of-principle analyte, this sensing platform can detect
      Tb specifically with a detection limit as low as 1.5 pM, which is at least 4
      orders of magnitude lower over the unamplified colorimetric assay. Moreover, the
      assay does not involve any chemical modification of DNA, which is simple and low
      cost. This sensing platform provides a promising approach for the amplified
      analysis of target molecules. 

PMID- 23534944
TI  - Low clinical utility of folate determinations in primary care setting.
AB  - BACKGROUND: Fortification of cereal products with folic acid is not mandatory in
      Israel, yet folate deficiency remains rare and is usually associated with poor
      diet, malabsorption, alcoholism, or use of certain drugs. A retrospective review
      of all folate level determinations performed between January 2004 and January
      2007 in the central district of Clalit Health Services in Israel revealed that
      only 4.3% of the 43,176 tests ordered were below the norm (5.6 nmol/L).
      OBJECTIVES: To determine parameters that identify folate-deficient patients
      without known risk factors and to establish principles that aid the physician in
      deciding when to order folate determinations. METHODS: Study population included
      152 patients from 13 large primary care clinics with folate deficiency but
      without known risk factors for folate deficiency (37 with anemia). They were
      matched with 556 controls (141 with anemia).The medical records were reviewed for
      the indication of the test and treatment that followed the results. RESULTS:
      Hematologic indices, vitamin B12, ferritin, and transferrin saturation levels
      were similar in the study and control groups. Subgroup comparisons based on
      anemia status showed similar results. The clinical indications for folate
      determinations were similar in the folate-deficient patients and the control
      group. Only 68 of 152 patients (44.7%) were prescribed a folate supplement.
      CONCLUSIONS: Neither laboratory parameters nor clinical findings in patients'
      charts were capable of distinguishing folate-deficient patients from controls. It
      seems that folate determinations in patients without known risk factors for
      folate deficiency are of little clinical significance.

PMID- 23534945
TI  - Trends in inpatient hospital prices, 2008 to 2010.
AB  - OBJECTIVES: Our goal was to present detailed descriptive data on transaction
      prices paid by commercial insurers and their enrollees for inpatient hospital
      care. DATA AND METHODS: To estimate transaction prices for inpatient hospital
      stays (hospital cost only), we used the MarketScan data set of commercial claims
      and administrative records for 45 to 50 million covered enrollees under age 65
      years with commercial group health insurance. Prices are defined as average
      allowed charges, including insurer-paid reimbursements plus patient costsharing
      obligations, and are shown for 350 specific admission categories and for many
      states and localities. Intensity adjustments to account for increased complexity
      or resource use in hospital stays were estimated from changes in the numbers of
      procedures per admission, the complexity of admission codes, and patients' risk
      scores. RESULTS: Unadjusted inpatient hospital prices per admission grew by 8.2%
      per year from 2008 to 2010 for the commercially insured population (under age 65
      years) in the MarketScan data set. We estimate that approximately 1.3 to 1.9
      percentage points of the growth in prices can be attributed to increased
      intensity per admission. Thus, we estimate that intensity-adjusted price
      increases ranged from 6.2% to 6.8% annually in the 2008-2010 period. Price levels
      and trends varied considerably across admission types, states, and localities.

PMID- 23534946
TI  - Factors associated with primary hip arthroplasty after hip fracture.
AB  - OBJECTIVES: To determine patient, clinical, and hospital factors associated with
      receiving total hip arthroplasty (THA) and hemiarthroplasty (HA) in the United
      States. STUDY DESIGN: Retrospective, cross-sectional study. METHODS: Hospital
      discharge records with a principal diagnosis of hip fracture and primary hip
      arthroplasty or no surgery were identified from the 2009 Nationwide Inpatient
      Sample data set of the Healthcare Cost and Utilization Project. Patient (age,
      sex, race, income, payer), clinical (comorbidities, severity, fracture type),
      hospital (region, location, teaching status, bed size, ownership), and outcome
      (receipt of THA or HA) variables were extracted and weighted for the analyses.
      Univariate and multivariate analysis were conducted and significance was set at P
      < .05. RESULTS: A total of 92,861, 15,489, and 9863 discharges occurred for HA,
      no surgery, and THA, respectively. Compared with no surgery, THA or HA was
      significantly more likely in patients who were aged > 50 years, white, and
      female; had > $39,000 income; lived in a medium-metro or noncore county; had
      comorbidities (anemia, hypertension); and had intracapsular fracture. THA or HA
      was significantly more likely in urban, privately owned hospitals with > 249
      beds. Compared with no surgery, THA was significantly more likely in nonteaching
      hospitals, the Northeast region, and in private insurance or self-pay patients
      with moderate to severe fractures; HA was more likely in teaching hospitals, in
      the South and West, and in Medicare patients with minor fractures. CONCLUSIONS:
      Similarities and differences in patient, clinical, and hospital factors
      associated with surgical treatments of hip fracture warrant the attention of
      providers and payers.

PMID- 23534948
TI  - Computed tomography scan use variation: patient, hospital, and geographic
      factors.
AB  - OBJECTIVES: To examine patient, hospital, and geographic characteristics
      influencing variation in computed tomography (CT) scan use in inpatients in New
      York State. STUDY DESIGN: Retrospective cohort study. METHODS: We used the 2007
      healthcare cost and utilization project's state inpatient database from the
      agency for healthcare research and quality and applied descriptive univariate
      statistics and logistic regression models to quantify the influence of each
      factor on CT scan use. RESULTS: The primary contributors to variation in CT scan
      use were the inpatients' diagnosis, age, and hospital county, whereas inpatients'
      sex and method of payment and hospitals' teaching status and size had very little
      effect. Inpatients diagnosed with trauma had the highest CT scan use; CT scan use
      increased with age for inpatients over 30 years; and CT scan use varied widely
      between counties. CONCLUSIONS: After controlling for patient and hospital
      characteristics, significant geographic variation remained at the level of the
      county, which indicates that additional research investigating the use of CT
      scans is necessary to understand the reasons behind small-area variation.
      Understanding the distribution and practice patterns of specific physician
      specialties may be helpful in curtailing underuse and overuse.

PMID- 23534947
TI  - Measuring concurrent oral hypoglycemic and antidepressant adherence and clinical
      outcomes.
AB  - OBJECTIVES: Many patients experience difficulty in adhering to medication for
      both physical and mental health. Our objective was to compare selfreported
      adherence and electronic monitoring of adherence to oral hypoglycemic agents and
      antidepressants and to examine the relationship of adherence with clinical
      outcomes. STUDY DESIGN: Primary care-based longitudinal study. METHODS: Adherence
      was assessed in 180 patients prescribed pharmacotherapy for type 2 diabetes
      mellitus (T2DM) and depression enrolled in a randomized controlled trial of an
      integrated intervention for depression and T2DM. Adherence data were collected
      using self report and electronic monitoring. Glycated hemoglobin (A1C) assays
      were used to measure glycemic control, and the 9-item patient health
      questionnaire assessed depression. RESULTS: At 12 weeks, self-reported adherence
      and electronic monitoring of adherence showed fair agreement (kappa = 0.213, P =
      .004 for oral hypoglycemic agents and kappa = 0.380, P < .001 for
      antidepressants). Patients who achieved >80% adherence to oral hypoglycemic
      agents measured with electronic monitoring were more likely to achieve A1C < 7%
      compared with patients who did not achieve > 80% adherence at 12 weeks (adjusted
      odds ratio = 3.52, 95% confidence interval 1.07-11.57). Self-reported adherence
      to oral hypoglycemic agents was not associated with diabetes outcomes. Measures
      of adherence for antidepressants were not associated with depression outcomes in
      models adjusted for potentially influential covariates. CONCLUSIONS: Compared
      with electronic monitoring of adherence, self-reported adherence tended to
      overestimate medication adherence. Electronic monitoring of adherence to oral
      hypoglycemic agents predicted glycemic control, but self-reported adherence did
      not predict clinical outcomes.

PMID- 23534949
TI  - Targeting of NF-kappaB signaling pathway, other signaling pathways and
      epigenetics in therapy of multiple myeloma.
AB  - Multiple myeloma (MM) remains an incurable disease, at least for the big majority
      of patients, in spite of the great progress with new drugs in the last years. New
      treatment strategies are needed to improve the outcome of patients. NF-kappaB
      activation in MM is caused by mutations in the factors involved in the NF-kappaB
      pathways contributing to their dysregulation and by signals from the bone marrow
      microenvironment. Agents with NF-kappaB inhibitory activity enhance the anti-MM
      effects of conventional chemotherapeutic agents. Bortezomib was the first
      approved member of a new class of anti-MM agents, the proteasome inhibitors. At
      least, five proteasome inhibitors of the next generation with greater efficacy
      (carfilzomib, marizomib (salinosporamide A, NPI-0052), threonine boronic acid
      derived proteasome inhibitor CEP-18770, the peptide-semicarbazone S-2209, the
      tripeptide mimetic BSc2118, and MLN9708/2238) have been recently tested in
      preclinical models of MM. Carfilzomib has been recently approved for the
      treatment of patients with MM who have received at least two prior therapies,
      including bortezomib and immunomodulatory derivatives (IMiDs, thalidomide,
      lenalidomide or pomalidomide). More specific IkappaB kinase inhibitors were also
      used in preclinical studies. The analysis of MM genomes revealed also mutations
      in genes for histone methyltransferases (HMTases), histone demethylase (UTX) and
      serine/threonine protein kinase BRAF. Aberrant histone 3 lysine 27 trimethylation
      (H3K27me3) by mutant HMTases or UTX induces overexpression of the homeobox A9
      (HOXA9) gene. HOXA9 is normally expressed in primitive bone marrow cells and is
      silenced when cells differentiate. HOXA9 is a MM oncogene and targeting of its
      expression by histone deacetylases inhibitors or by a phosphoinositide 3-kinase
      (PI3K) inhibitors through an epigenetic mechanism involving H3K27me3. Mutant BRAF
      kinase small-molecule, ATP-competitive, a highly selective, potent and orally
      bioavailable inhibitors (GDC-0879, PLX 4032 and PLX 4720) are already under
      investigation and PLX 4032 is in phase II and phase III clinical trials. Two key
      signaling pathways involved in the regulation of MM cell growth are the
      Ras/Raf/MEK/ERK and PI3K/Akt/mTOR pathways and their inhibition are anti
      proliferative and pro-apoptotic and can overcome the development of resistance to
      common drugs.

PMID- 23534950
TI  - Glucose-6-phosphate dehydrogenase deficiency: disadvantages and possible
      benefits.
AB  - We review here some recent data about Glucose-6-phosphate dehydrogenase (G6PD),
      the housekeeping X-linked gene encoding the first enzyme of the pentose phosphate
      pathway (PPP), a NADPH-producing dehydrogenase. This enzyme has been popular
      among clinicians, biochemists, geneticists and molecular biologists because it is
      the most common form of red blood cell enzymopathy. G6PD deficient erythrocytes
      do not generate NADPH in any other way than through the PPP and for this reason
      they are more susceptible than any other cells to oxidative damage. Moreover,
      this enzyme has also been of crucial importance in many significant discoveries;
      indeed, G6PD polymorphisms have been instrumental in studying X-inactivation in
      the human species, as well as in establishing the clonal nature of certain
      tumors. G6PD deficiency, generally considered as a mild and benign condition, is
      significantly disadvantageous in certain environmental conditions like in
      presence of certain drugs. Nevertheless, G6PD deficiency has been positively
      selected by malaria, and recent knowledge seems to show that it also confers an
      advantage against the development of cancer, reduces the risk of coronary
      diseases and has a beneficial effect in terms of longevity.

PMID- 23534951
TI  - Updated role of nitric oxide in disorders of erythrocyte function.
AB  - Nitric oxide is a potent vasodilator that plays a critical role in disorders of
      erythrocyte function. Sickle cell disease, paroxysmal nocturnal hemoglobinuria
      and banked blood preservation are three conditions where nitric oxide is
      intimately related to dysfunctional erythrocytes. These conditions are
      accompanied by hemolysis, thrombosis and vasoocclusion. Our understanding of the
      interaction between nitric oxide, hemoglobin, and the vasculature is constantly
      evolving, and by defining this role we can better direct trials aimed at
      improving the treatments of disorders of erythrocyte function. Here we briefly
      discuss nitric oxide's interaction with hemoglobin through the hypothesis
      regarding Snitrosohemoglobin, deoxyhemoglobin, and myoglobin as nitrite
      reductases. We then review the current understanding of the role of nitric oxide
      in sickle cell disease, paroxysmal nocturnal hemoglobinuria, and banked blood,
      and discuss therapeutics in development to target nitric oxide in the treatment
      of some of these disorders.

PMID- 23534952
TI  - Phenylephrine as a simulated intravascular epidural test dose in pediatrics: a
      pilot study.
AB  - BACKGROUND: A test dose is used to detect intravascular injection during
      neuraxial block in pediatrics. Accidental intravascular epidural local anesthetic
      injection might be unrecognized in anesthetized children leading to potential
      life-threatening complications. In children, sevoflurane anesthesia blunts the
      hemodynamic response when intravascular cathecolamines are administered. No
      studies have explored the hemodynamics and the criteria for a positive test dose
      result following phenylephrine in sevoflurane anesthetized children. METHODS:
      Healthy children undergoing minor procedures were randomly assigned to receive
      intravenous placebo, or 5 MUg?kg(-1) phenylephrine (n = 11/group) during
      sevoflurane anesthesia. Hemodynamic response was assessed using
      electrocardiography, pulse oxymetry and non-invasive blood pressure monitoring
      for 5 min following drug administration in anesthetized patients. RESULTS: All
      patients receiving phenylephrine showed a decreased heart rate (HR) but not all
      of them met the positive criterion for test dose response. Overall, at 1 min,
      patients receiving phenylephrine showed a 25% decrease in HR from the baseline
      while an increase in blood pressure was noticed in 54% of patients receiving
      phenylephrine. DISCUSSION: Phenylephrine might be a future indicator of positive
      intravascular test dose. Further investigation is needed to find out the
      phenylephrine dose that elicits a reliable hemodynamic response and whether
      phenylephrine needs to be dose age-adjusted in order to appreciate relevant
      hemodynamic changes in children receiving neuraxial blocks undergoing general
      anesthesia.

PMID- 23534954
TI  - Combination therapy of natural human interferon-beta and ribavirin for chronic
      hepatitis C patients with injection drug use.
AB  - AIM: The aim of this study was to evaluate the efficacy and safety of combination
      therapy using natural human interferon-beta and ribavirin (IFN-beta/RBV) for
      chronic hepatitis C patients who were injection drug users (IDU) and resident in
      the Airin district of Osaka, containing the biggest slums in Japan. METHODS:
      Twenty-nine IDU with chronic hepatitis C received combination therapy of IFN
      beta/RBV. The psychiatrist in charge evaluated the scores of the Zung Self-rating
      Depression Scale (SDS), a self-rating scale based on 20 questions. Univariate
      logistic regression analyses were used to determine the factors that
      significantly contributed to complete treatment and a sustained virological
      response (SVR). RESULTS: Thirteen of the 29 patients achieved SVR according to
      the intention to treat analysis. All patients with a rapid virological response
      achieved SVR. No patient required a reduced dose of RBV because of a decrease in
      their hemoglobin level, or of IFN-beta because of a low level of white blood
      cells and platelet count. Two patients had psychological side-effects and stopped
      the therapy early in the treatment; one patient had depression and the other had
      anxious depression. Univariate logistic regression analyses indicated that the
      stage of fibrosis was the only factor that contributed to SVR, and that the SDS
      test and past drug abuse contributed to completion of the treatment. CONCLUSION:
      IFN-beta/RBV combination therapy is useful for treating IDU.

PMID- 23534953
TI  - Mass spectrometry-guided optimization and characterization of a biologically
      active transferrin-lysozyme model drug conjugate.
AB  - Transferrin is a promising drug carrier that has the potential to deliver metals,
      small organic molecules and therapeutic proteins to cancer cells and/or across
      physiological barriers (such as the blood-brain barrier). Despite this promise,
      very few transferrin-based therapeutics have been developed and reached clinical
      trials. This modest success record can be explained by the complexity and
      heterogeneity of protein conjugation products, which also pose great challenges
      to their analytical characterization. In this work, we use lysozyme conjugated to
      transferrin as a model therapeutic that targets the central nervous system (where
      its bacteriostatic properties may be exploited to control infection) and develop
      analytical protocols based on electrospray ionization mass spectrometry to
      characterize its structure and interactions with therapeutic targets and
      physiological partners critical for its successful delivery. Mass spectrometry
      has already become an indispensable tool facilitating all stages of the protein
      drug development process, and this work demonstrates the enormous potential of
      this technique in facilitating the development of a range of therapeutically
      effective protein-drug conjugates.

PMID- 23534955
TI  - Similarity in dissymmetry factor spectra: a quantitative measure of comparison
      between experimental and predicted vibrational circular dichroism.
AB  - To quantitatively determine the agreement between experimental and calculated
      vibrational circular dichroism (VCD) spectra, a new approach, based on the
      similarity of dissymmetry factor spectra has been developed and implemented. This
      method, which places emphasis on robust regions both in the experimental and in
      the calculated spectra, has been tested with six chiral compounds of known
      absolute configurations, namely, (R)-(+)-3-chloro-1-butyne, (3R)-(+)
      methylcyclopentanone, (3R)-(+)-methylcyclohexanone, (1S)-(-)-alpha-pinene, (1R)
      (+)-camphor, and (S)-(+)-epichlorohydrin. The criterion of maximum overlap among
      experimental and calculated dissymmetry factor spectra is shown to have definite
      advantages over those using maximum overlap among VCD or absorption spectra
      individually. The new method provides a better assessment of the comparison
      between experimental observations and quantum chemical VCD predictions and
      improves the confidence in the assignment of absolute configurations.

PMID- 23534956
TI  - IGF1 mRNA splicing variants in Liaoning cashmere goat: identification,
      characterization, and transcriptional patterns in skin and visceral organs.
AB  - Insulin-like growth factor I (IGF1) is a member of the insulin superfamily. It
      performs important roles in the proliferation and differentiation of skin cell
      and control of hair cycles and is thought to be a potential candidate gene for
      goat cashmere traits. In this work, we isolated and characterized three kinds of
      IGF1 mRNA splicing variants from the liver of Liaoning Cashmere goat, and the
      expression characterization of the IGF1 mRNA splicing variants were investigated
      in skin and other tissues of Liaoning cashmere goat. The sequencing results
      indicated that the classes 1w, 1, and 2 of IGF1 cDNAs in Liaoning cashmere goat,
      each included an open reading frame encoding the IGF1 precursor protein. The
      deduced amino acid sequences of the three IGF1 precursor proteins differed only
      in their NH2-terminal leader peptides. Through removal of the signal peptide and
      extension peptide, the three IGF1 mRNA splicing variants (classes 1w, 1, and 2)
      resulted in the same mature IGF1 protein in Liaoning cashmere goat. In skin
      tissue of Liaoning cashmere goat, class 1 and class 2 were detected in all stages
      of hair follicle cycling, and they had the highest transcription level at anagen,
      and then early anagen; whereas at telogen both classes 1 and 2 had the lowest
      expression in mRNA level, but the class 1 appears to be relatively more abundant
      than class 2 in skin tissue of Liaoning cashmere goat. However, the class 1w
      transcript was not detected in the skin tissues. Three classes of IGF1 mRNA were
      transcribed in a variety of tissues, including heart, brain, spleen, lung,
      kidney, liver, and skeletal muscle, but class 1 IGF1 mRNA was more abundant than
      classes 1w and 2 in the investigated tissues.

PMID- 23534957
TI  - Bovine oocytes cryoinjury and how to improve their development following
      cryopreservation.
AB  - Bovine oocytes are less likely to undergo successful cryopreservation than
      cleavage-stage embryos. Bovine oocytes characteristically contain high levels of
      lipids that represent one of the major obstacles limiting efficient
      cryopreservation. These droplets together with structures such as cumulus cells,
      zona pellucida, cytoplasm membrane, cortical granules, mitochondria, spindle, and
      cytoskeleton (microtubles and microfilaments) often incur serious damage during
      cooling and warming. The cryoinjury could, to some extent, be decreased by
      selection of proper permeable and non-permeable cryoprotectants, and of
      vitrification with high cooling and warming rates. Additionally, such measures
      may also enhance their cryotolerance as partial removal of cumulus cells,
      modification of oocyte membrane constituents, polarization of the cytoplasmic
      lipid droplets by centrifugation, and addition of cytoskeleton relaxants or ice
      blockers into vitrification solutions. The improvement in cryopreservation
      methodology for bovine oocytes will no doubt augment other technologies such as
      bovine cloning and the establishment of gene bank for transgenic cattle.

PMID- 23534958
TI  - Ammonia assimilation in rumen bacteria: a review.
AB  - In the rumen bacteria, ammonia as the end product of nitrogen is incorporated
      into carbon skeleton (alpha-ketoglutarate) to yield glutamine and glutamate which
      are important nitrogen donors in nitrogenous compounds metabolism in cells. The
      enzymes glutamine synthetase, glutamate synthetase, and glutamate dehydrogenase
      are involved in these processes. Some experimental results have proven that the
      global nitrogen regulation system may participate in the regulation of
      assimilation of ammonia in rumen bacteria. This review offers a current
      perspective on the pathways and key enzymes of ammonia assimilation in rumen
      bacteria with the possible molecular regulation strategy, while points out the
      further research direction.

PMID- 23534959
TI  - Site-specific N-glycosylation of caprine lysostaphin restricts its bacteriolytic
      activity toward Staphylococcus aureus.
AB  - Lysostaphin (LYS) is an anti-staphylococcal prokaryotic polypeptide that has been
      used to avoid Staphylococcus aureus mastitis through transgenic or viral vector
      approaches exogenously expressed in dairy animals. However, glycosylation of
      lysostaphin expressed in mammalian cells results in a loss of bioactivity. Until
      now, the mechanism of site-specific glycosylation of lysostaphin causing this
      loss of bioactivity remains unknown. An immortalized caprine mammary epithelial
      cell line (CMEC-08-D) was used to study recombinant lysostaphin fused with goat
      beta-casein, goat lactoferrin (LF) or prokaryotic signal peptides. These
      constructs were separately ectopically expressed in CMEC-08-D. Results of site
      directed mutagenesis show that Asn(125) but not Asn(232) is the exact
      glycosylation site of lysostaphin expressed in CMEC-08-D. In addition, the effect
      of glycosylation of lysostaphin on its staphylolytic activity was identified
      through bacterial plate assay. The data indicated that wild type and mutated
      N232Q-lysostaphin (Asn(232) to Gln(232) substitution) lacked staphylolytic
      activity. In contrast, mutated N125Q (Asn(125) to Gln(125) substitution) and
      N125Q/N232Q-lysostaphin possessed staphylolytic activity. On the other hand, all
      mutated lysostaphin showed no change in binding ability to S. aureus. This
      reveals that N-glycosylation at Asn(125) of lysostaphin expressed in a eukaryotic
      system greatly decreases lysostaphin bacteriolytic activity but does not affect
      its binding ability to S. aureus.

PMID- 23534960
TI  - Genetic structuring of nine Indian domestic goat breeds based on SNPs identified
      in IGF-1 gene.
AB  - The caprine Insulin like Growth Factor1 (IGF1) gene was analyzed for
      identification of single nucleotide polymorphisms (SNPs) and genetic structuring
      of Indian goat breeds. A panel of 80 samples belonging to nine Indian goat breeds
      (Capra hircus) including three large sized breeds (Jamunapari, Beetal and
      Jakhrana); three medium sized breeds (Sirohi, Barbari, and Osmanabadi) and three
      small sized breeds (Black Bengal, Changthangi, and Gaddi) were screened for SNP
      identification and diversity analysis. The comparative gene sequence analysis of
      all the nine goat breeds studied revealed a total of 18 SNPs in IGF1 gene. All
      the nucleotide changes were found to be synonymous. The mean observed
      heterozygosity was found to be maximum (0.074) in Sirohi, Beetal, Osmanabadi, and
      Gaddi breeds of goat, whereas it is found to be minimum (0.019) in Black Bengal
      breed of goat. The rest of the breeds were intermediate in terms of
      heterozygosity. The same has been confirmed by allele frequency distribution
      across the studied loci. Barbari and Gaddi were found to be more differentiated
      (0.0123), Changthangi and Jamunapari were least differentiated (0.00110) based on
      Nei's genetic distance.

PMID- 23534961
TI  - Role of neuropilin-2 in the ipsilateral growth of midbrain dopaminergic axons.
AB  - Axonal projections in the CNS can be categorized as either crossed or uncrossed.
      Crossing and uncrossing of axons has been explained by attractive and repulsive
      molecules like Netrin-1 and Slits, which are secreted by midline structures.
      However, uncrossed projections can be established even in double knockout mice of
      slit1 and slit2 or of roundabout1 (robo1) and robo2, two receptors for Slits.
      Here, we found that a novel mechanism mediated by Neuropilin-2 (Nrp2) contributes
      to the formation of uncrossed projections of midbrain dopaminergic neurons
      (mDANs). Nrp2 transcriptional activities were detected in a subset of mDANs, and
      its protein was expressed in mDAN axons growing through the ipsilateral
      diencephalon. In nrp2(lac) (Z) (/lac) (Z) mice, mDAN axons aberrantly grew toward
      the ventral midline and even crossed it, suggesting that Nrp2 is necessary for
      the development of mDAN ipsilateral projections. We investigated the involvement
      of Semaphorin 3B (Sema3B) and Sema3F, two ligands of Nrp2, by analysing mDAN axon
      trajectories in single or double knockout mice. In both cases, mDAN axons still
      projected ipsilaterally, suggesting the involvement mechanisms independent of
      these Sema3s. Nrp2-deficient mDAN axons retained their responsiveness to Slit2,
      demonstrating that aberrant mDAN axons in nrp2(lac) (Z) (/lac) (Z) mice were not
      indirectly mediated by alterations in Slit/Robo signaling. Taken together, our
      results indicate that a novel mechanism mediated by Nrp2 contributes to the
      establishment of uncrossed projections by mDAN axons.

PMID- 23534962
TI  - Vasculitides: roads traveled and avenue to pursue.

PMID- 23534963
TI  - Target blood pressure in sepsis: between a rock and a hard place.
AB  - The optimal target blood pressure in septic shock is still unknown. Therefore, in
      a long-term, resuscitated porcine model of fecal peritonitis-induced septic
      shock, Correa and colleagues tested whether different titrations of mean arterial
      pressure (50 to 60 and 75 to 85 mm Hg) would produce different effects on sepsis
      related organ dysfunction. The higher blood pressure window was associated with
      increased needs for fluid resuscitation and norepinephrine support. However,
      titrating the lower blood pressure range coincided with an increased incidence of
      acute kidney injury. In contrast, neither the inflammatory response nor tissue
      mitochondrial activity showed any difference. This research paper in a clinically
      relevant model elegantly demonstrates that any standard resuscitation strategy
      may be a double-edged sword with respect to various therapeutic endpoints.
      Furthermore, it adds an important piece to the puzzle of the complex
      pathophysiology of sepsis-related acute kidney injury. 

PMID- 23534964
TI  - Service-related needs of older people with dementia: perspectives of service
      users and their unpaid carers.
AB  - BACKGROUND: Dementia is a major cause of disability among older people and
      constitutes one of the greatest challenges currently facing families and health
      and social care services in the developed world. In response to trends in
      dementia prevalence and the impact the condition has on peoples' lives, dementia
      care has been placed high on the public and political agenda in the United
      Kingdom. However, despite significant public resources being allocated to combat
      the impact of the disease, recent evidence indicates that numerous challenges in
      relation to service provision remain. This study aimed to develop a deeper
      understanding of the lived experience of people with dementia regarding their
      service-related needs. METHOD: The study made use of data gathered through
      individual semi-structured, narrative interviews conducted with persons with
      experience of dementia and their unpaid carers. RESULTS: Although participants
      were generally satisfied with the services they received, a number of unmet needs
      related to service provision were identified. In terms of diagnostic procedures
      the findings of this study indicate the need for early diagnosis delivered
      through a comprehensive assessment package. The participants also highlighted the
      need for well-coordinated post-diagnostic support, greater continuity of care
      concerning the personnel involved, and enhanced access to non-pharmacological
      interventions to support identity and social engagement. CONCLUSION: This study
      contributes to a better understanding of service-related needs of people with
      dementia in relation to diagnostic procedures and post-diagnostic support.

PMID- 23534968
TI  - Mechanistic insight into self-propagation of organo-mediated Beckmann
      rearrangement: a combined experimental and computational study.
AB  - Organo-mediated Beckmann rearrangement in the liquid phase, which has the
      advantage of high efficiency and straightforward experimental procedures, plays
      an important role in the synthesis of amides from oximes. However, the catalytic
      mechanisms of these organic-based promoters are still not well understood. In
      this work, we report a combined experimental and computational study on the
      mechanism of Beckmann rearrangement mediated by organic-based promoters, using
      TsCl as an example. A novel self-propagating cycle is proposed, and key
      intermediates of this self-propagating cycle are confirmed by both experiments
      and DFT calculations. In addition, the reason why cyclohexanone oxime is not a
      good substrate of the organo-mediated Beckmann rearrangement is discussed, and a
      strategy for improving the yield is proposed.

PMID- 23534969
TI  - The acute chest syndrome of sickle cell disease.
AB  - INTRODUCTION: Acute chest syndrome (ACS), a leading cause of morbidity and
      mortality in sickle cell disease (SCD), is an acute illness characterized by
      fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a
      chest X-ray. There is increasing knowledge regarding the etiology and
      pathogenesis of ACS in SCD. A high index of suspicion is required for the
      diagnosis of ACS. Treatment of ACS involves the judicious use of intravenous
      fluids and analgesics, aggressive incentive spirometer and pulmonary toileting,
      antibiotics and transfusion therapy. AREAS COVERED: This review evaluates the
      epidemiology, clinical and laboratory presentation, etiology and pathogenesis of
      ACS. It also reviews the standard treatments as well as experimental treatments
      in ACS. EXPERT OPINION: Despite an increased understanding of its etiology and
      pathogenesis, ACS remains a leading cause of morbidity and mortality in SCD. In
      patients admitted with a painful crisis, there is need for a high index of
      suspicion, as pain episodes may be a prodrome for the development of ACS.
      Patients with a diagnosis of ACS should be aggressively managed to prevent
      clinical deterioration. Clinical trials using novel drugs for the treatment of
      ACS are greatly warranted.

PMID- 23534970
TI  - Reusable photocatalytic titanium dioxide-cellulose nanofiber films.
AB  - Titanium dioxide (TiO2) is a well-studied photocatalyst that is known to break
      down organic molecules upon ultraviolet (UV) irradiation. Cellulose nanofibers
      (CNFs) act as an attractive matrix material for the suspension of photocatalytic
      particles due to their desirable mechanical and optical properties. In this work,
      TiO2-CNF composite films were fabricated and evaluated for photocatalytic
      activity under UV light and their potential to remove organic compounds from
      water. Subsequently, gold (Au) and silver (Ag) nanoclusters were formed on the
      film surfaces using simple reduction techniques. Au and Ag doped TiO2 films
      showed a wider spectral range for photocatalysis and enhanced mechanical
      properties. Scanning electron microscopy imaging and energy dispersive X-ray
      spectroscopy mapping were used to evaluate changes in microstructure of the films
      and monitor the dispersion of the TiO2, Au, and Ag particles. The ability of the
      films to degrade methylene blue (a model organic dye) in simulated sunlight has
      been demonstrated using UV-visible spectroscopy. Reusability and mechanical
      integrity of the films were also investigated.

PMID- 23534971
TI  - The role of lectins in allergic sensitization and allergic disease.
AB  - Allergic diseases are a global public health issue affecting millions of persons
      around the world. However, full understanding of the molecular basis of this
      group of chronic inflammatory disorders remains rather elusive. Recently, the
      role of carbohydrates on allergens and their counterstructures on antigen
      presenting cells (lectins) have been highlighted as crucial factors in allergen
      sensitization, which culminates in TH2 cell differentiation and the production of
      deleterious specific IgE antibodies. Here we review recent progress on the role
      of different lectins in patients with type I hypersensitivity or allergy, their
      interplay with other determinants of allergenicity, and ways of developing
      therapeutic modalities against newly identified targets. 

PMID- 23534972
TI  - Are leukocytes in asthmatic patients aging faster? A study of telomere length and
      disease severity.

PMID- 23534973
TI  - Maternal asthma and microRNA regulation of soluble HLA-G in the airway.
AB  - BACKGROUND: We previously reported an interaction between maternal asthma and the
      child's HLA-G genotype on the child's subsequent risk for asthma. The implicated
      single nucleotide polymorphism at +3142 disrupted a target site for the microRNA
      (miR)-152 family. We hypothesized that the interaction effect might be mediated
      by these miRs. OBJECTIVE: The objective of this study was to test this hypothesis
      in adults with asthma who are a subset of the same subjects who participated in
      our earlier family-based studies. METHODS: We measured soluble HLA-G (sHLA-G)
      concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from
      adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR
      152 family (miR-148a, miR-148b, and miR-152) transcript levels in airway
      epithelial cells from the same subjects. RESULTS: miR-148b levels were
      significantly increased in airway epithelial cells from asthmatic subjects with
      an asthmatic mother compared with those seen in asthmatic subjects without an
      asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations
      in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother
      but not among those with a nonasthmatic mother. Neither effect was observed in
      the plasma (sHLA-G) or white blood cells (miRNA). CONCLUSION: These combined
      results are consistent with +3142 allele-specific targeting of HLA-G by the miR
      152 family and support our hypothesis that miRNA regulation of sHLA-G in the
      airway is influenced by both the asthma status of the subject's mother and the
      subject's genotype. Moreover, we demonstrate that the effects of maternal asthma
      on the gene regulatory landscape in the airways of the mother's children persist
      into adulthood.

PMID- 23534975
TI  - Sublingual versus oral immunotherapy for peanut-allergic children: a
      retrospective comparison.

PMID- 23534974
TI  - Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation
      polyendocrinopathy-enteropathy-X-linked-like syndrome.
AB  - BACKGROUND: Mutations in signal transducer and activator of transcription (STAT)
      1 cause a broad spectrum of disease, ranging from severe viral and bacterial
      infections (amorphic alleles) to mild disseminated mycobacterial disease
      (hypomorphic alleles) to chronic mucocutaneous candidiasis (CMC; hypermorphic
      alleles). The hypermorphic mutations are also associated with arterial aneurysms,
      autoimmunity, and squamous cell cancers. OBJECTIVE: We sought to investigate the
      role of STAT1 gain-of-function mutations in phenotypes other than CMC. METHODS:
      We initially screened patients with CMC and autoimmunity for STAT1 mutations. We
      functionally characterized mutations in vitro and studied immune profiles and
      regulatory T (Treg) cells. After our initial case identifications, we explored 2
      large cohorts of patients with wild-type forkhead box protein 3 and an immune
      dysregulation-polyendocrinopathy-enteropathy-X-linked (IPEX)-like phenotype for
      STAT1 mutations. RESULTS: We identified 5 children with polyendocrinopathy,
      enteropathy, and dermatitis reminiscent of IPEX syndrome; all but 1 had a variety
      of mucosal and disseminated fungal infections. All patients lacked forkhead box
      protein 3 mutations but had uniallelic STAT1 mutations (c.629 G>T, p.R210I;
      c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M [2 patients]). STAT1
      phosphorylation in response to IFN-gamma, IL-6, and IL-21 was increased and
      prolonged. CD4(+) IL-17-producing T-cell numbers were diminished. All patients
      had normal Treg cell percentages in the CD4(+) T-cell compartment, and their
      function was intact in the 2 patients tested. Patients with cells available for
      study had normal levels of IL-2-induced STAT5 phosphorylation. CONCLUSIONS: Gain
      of-function mutations in STAT1 can cause an IPEX-like phenotype with normal
      frequency and function of Treg cells.

PMID- 23534977
TI  - Eccrine nevus affecting the forearm of an 11-year-old girl successfully
      controlled with topical glycopyrrolate.
AB  - Eccrine nevi are rare lesions characterized by a sharply demarcated area of
      localized hyperhidrosis. We present an 11-year-old girl with an eccrine nevus on
      her right lower forearm. To the best of our knowledge, this is the first case
      successfully controlled with topical glycopyrrolate wipes. 

PMID- 23534976
TI  - B-cell linker protein expression contributes to controlling allergic and
      autoimmune diseases by mediating IL-10 production in regulatory B cells.
AB  - BACKGROUND: Regulatory B cells that exhibit the cell-surface CD1d(hi)CD5(+)
      phenotype and produce IL-10 are termed B10 cells. Although B10 cells exert potent
      suppressive functions in patients with various allergic and autoimmunity
      disorders, the precise signaling mechanisms required for B10 cell functions
      remain unknown. B-cell linker protein (BLNK) is an essential component of the B
      cell antigen receptor signaling pathway and is required for optimal B-cell
      development. OBJECTIVE: We sought to elucidate the signaling pathways that are
      responsible for IL-10 production in B10 cells and in vivo mechanisms of how
      impaired B10 cell functions influence allergic and autoimmune responses. METHOD:
      For in vitro assays, splenic CD1d(hi)CD5(+) B cells from BLNK-deficient (BLNK(-/
      )) mice were analyzed for intracellular signaling pathways and cytokine
      production. Contact hypersensitivity (CHS) and experimental autoimmune
      encephalomyelitis were examined by using BLNK(-/-) mice. RESULTS: Although the
      CD1d(hi)CD5(+) B-cell population was present in BLNK(-/-) mice, IL-10 production
      was impaired both in vitro and in vivo. BLNK(-/-) mice had exaggerated CHS and
      experimental autoimmune encephalomyelitis responses, which were normalized by
      adoptive transfer of splenic CD1d(hi)CD5(+) B cells from wild-type mice. In mice
      with CHS, BLNK(-/-) mice exhibited decreased B-cell and regulatory T-cell
      percentages and increased CD8(+) T-cell percentages in the skin and lymph nodes.
      In vitro BLNK was required for LPS-induced signal transducer and activator of
      transcription 3 phosphorylation in CD1d(hi)CD5(+) B cells. Finally, secreted IL
      10 leads to autocrine expansion of IL-10-producing B cells. CONCLUSION: BLNK
      serves as a critical signaling component for B10 cell function by mediating IL-10
      production.

PMID- 23534979
TI  - Is it possible to use the rectus abdominis neo-sphincter as a continence
      mechanism for urinary catheterizable channels? A histologic and histochemical
      evaluation in an experimental study in rabbits.
AB  - OBJECTIVE: To evaluate in a rabbit experimental model a mechanism of continence
      of catheterizable urinary conduits (CUC), focusing on the behavior of intersected
      rectal muscle fibers in relation to the channel by histological and histochemical
      analysis, and secondarily to register conduit continence rates from clinical and
      urodynamic data. MATERIALS AND METHODS: 12 rabbits were submitted to construction
      of a CUC from two abdominal skin flaps and divided into two groups: 8 with a
      urinary neo-sphincter created according to Yachia and 4 controls. We registered
      clinical outcome, urodynamic studies and microscopic analysis of CUC on the
      surface of the conduit, which was in direct contact with the mechanism of
      continence. We took muscle samples from the mechanisms of continence and
      performed histochemical evaluation by enzymatic reactions. RESULTS: Histological
      evaluation of the CUC showed no difference between groups. Histology and
      immunohistochemistry of the muscle fibers showed that areas of necrosis, cell
      atrophy and motor neuron injury from the first eight weeks recovered by the end
      of 16th week. Conduit complications occurred in 4 animals (33%). The average
      detrusor leakage point pressure through the conduit was 90 cm H2O versus 39 cm
      H2O through the urethra. CONCLUSION: The mechanism of continence did not promote
      ischemic stress on the conduit, was able to promote high pressure resistance and
      showed good recovery of intersected muscle fibers, after an initial slight
      atrophy, suggesting good durability of the neo-sphincter.

PMID- 23534980
TI  - TNF-alpha and melphalan modulate a specific group of early expressed genes in a
      murine melanoma model.
AB  - BACKGROUND: Cutaneous melanoma displays high morbidity and mortality rates.
      Isolated limb perfusion with melphalan (Mel) is used for the treatment of non
      resectable, locally advanced extremity melanomas. When combined with tumor
      necrosis factor alpha (TNF-alpha) treatment, the complete response varies between
      70% and 90%. The mechanisms underlying the effects of Mel and TNF-alpha are not
      completely understood. We evaluated the impact of systemic Mel and TNF-alpha
      administration on tumor growth, analyzed the morphological changes promoted by
      each treatment, and identified early expressed genes in response to Mel and TNF
      alpha treatment, either alone or in combination, in a murine melanoma model.
      METHODS: Six- to eight-week-old male mice were subcutaneously inoculated with
      B16F10 melanoma cells and then intravenously injected with TNF-alpha, melphalan
      or a combination of both drugs when the tumors reached 1.0 cm(2). Tumor growth
      was monitored every other day, and histological analysis was performed when the
      tumors reached 3.0 cm(2). Total RNA was extracted from the resected tumors and
      submitted to amplification, labeling and hybridization on an oligonucleotide
      microarray (Fox Chase Cancer Center). Tumor growth and histological parameters
      were compared using ANOVA. Survival curves were calculated using the Kaplan-Meier
      method. Two-way ANOVA was used to identify differentially expressed genes among
      the various treatments, and Dunn's test was used for pair-wise comparisons.
      RESULTS: Systemic administration of Mel impaired tumor growth (p<0.001), improved
      animal survival (p<0.001), and decreased mitotic rate (p=0.049). Treatment with
      TNF-alpha alone had no impact, neither on tumor growth, nor on survival, but it
      increased necrosis (p<0.024) and decreased mitotic rates (p=0.001) in the tumors.
      Combined treatment with Mel and TNF-alpha had similar effects in tumor growth,
      survival, necrosis and mitotic rate as observed with individual treatments.
      Moreover, 118 genes were found differentially expressed by microarray analysis
      and 10% of them were validated by RT- real time PCR. In our model we found that
      the treatments regulate genes that play important roles in tumorigenesis such as
      cell adhesion (Pard3, Pecam1, Ilk, and Dlg5), proliferation (Tcfe3 and Polr1e),
      cell motility (Kifap3, Palld, and Arhgef6), apoptosis (Bcl2l11), and angiogenesis
      (Flt1 and Ptprj). CONCLUSIONS: Our data reproduces, in mice, some of the features
      observed in melanoma patients treated with the combination of Mel and TNF-alpha.
      The identification of genes with altered expression by these drugs both
      individually and in combination might help in the understanding of their
      mechanism of action and, as a consequence, improved strategies that could impact
      their clinical application.

PMID- 23534981
TI  - Biological interactions between soil saprotrophic fungi and Ascaris suum eggs.
AB  - The in vitro effect of saprotrophic soil fungi on the embryonic development of
      Ascaris suum was evaluated. The fungi tested were Aspergillus fumigatus,
      Aspergillus terreus, Penicillium citrinum, Penicillium expansum, Fusarium
      oxysporum and Trichothecium roseum, isolated from children's recreation areas in
      the city of Lodz (Poland). Each species was co-cultured with A. suum egg
      suspension (6 * 10(3)eggs/ml) at 25 +/- 2 degrees C for 60 days. Each day, 100
      eggs were randomly collected and their developmental stage was classified
      macroscopically. Additionally, at days 4, 7, 14, 28, 42 and 60 of incubation, the
      viability and the percentage of eggs with morphological altered embryo/larva were
      determined in each sample. Microscopic examination revealed that exposure of eggs
      to the mycelium of examined fungi inhibited embryogenesis of A. suum. All control
      culture eggs reached L2 larval stage after 26 days of incubation, while the
      experimental cultures did so after 32-51 days, depending on the fungal species.
      Three species were found to exhibit very high inhibitory activity on A. suum egg
      development: A. terreus, P. expansum and F. oxysporum. Embryopathies and non
      viable embryos/larvae were observed significantly more frequently in the eggs co
      cultured with fungal species than in control cultures. The fungus-exposed eggs
      revealed morphological alternations in the early zygotic cleavage, blastula,
      gastrula and larval stages. After 60 days of incubation with mycelia of P.
      expansum, A. terreus and F. oxysporum, the mortality of the larvae reached 55.3
      60.3%. P. expansum and F. oxysporum showed hyphal penetration and internal egg
      colonization of A. suum eggs.

PMID- 23534982
TI  - Direct and carryover effect of post-grazing sward height on total lactation dairy
      cow performance.
AB  - Grazing pastures to low post-grazing sward heights (PGSH) is a strategy to
      maximise the quantity of grazed grass in the diet of dairy cows within temperate
      grass-based systems. Within Irish spring-calving systems, it was hypothesised
      that grazing swards to very low PGSH would increase herbage availability during
      early lactation but would reduce dairy cow performance, the effect of which would
      persist in subsequent lactation performance when compared with cows grazing to a
      higher PGSH. Seventy-two Holstein-Friesian dairy cows (mean calving date, 12
      February) were randomly assigned post-calving across two PGSH treatments (n =
      36): 2.7 cm (severe; S1) and 3.5 cm (moderate; M1), which were applied from 10
      February to 18 April (period 1; P1). This was followed by a carryover period
      (period 2; P2) during which cows were randomly reassigned within their P1
      treatment across two further PGSH (n = 18): 3.5 cm (severe, SS and MS) and 4.5 cm
      (moderate, SM and MM) until 30 October. Decreasing PGSH from 3.5 to 2.7 cm
      significantly decreased milk (-2.3 kg/cow per day), protein (-95 g/day), fat (
      143 g/day) and lactose (-109 g/day) yields, milk protein (-1.2 g/kg) and fat (
      2.2 g/kg) concentrations and grass dry matter intake (GDMI; -1.7 kg dry
      matter/cow per day). The severe PGSH was associated with a lower bodyweight (BW)
      at the end of P1. There was no carryover effect of P1 PGSH on subsequent milk or
      milk solids yields in P2, but PGSH had a significant carryover effect on milk fat
      and lactose concentrations. Animals severely restricted at pasture in early
      spring had a higher BW and slightly higher body condition score in later
      lactation when compared with M1 animals. During P2, increasing PGSH from 3.5 to
      4.5 cm increased milk and milk solids yield as a result of greater GDMI and
      resulted in higher mean BW and end BW. This study indicates that following a 10
      week period of feed restriction, subsequent dairy cow cumulative milk production
      is unaffected. However, the substantial loss in milk solid yield that occurred
      during the period of restriction is not recovered. 

PMID- 23534983
TI  - Symptomatic exercise-induced left ventricular outflow tract obstruction without
      left ventricular hypertrophy.
AB  - BACKGROUND: Left ventricular (LV) outflow tract obstruction (LVOTO) is most
      commonly seen in patients with hypertrophic cardiomyopathy. Postexercise dynamic
      LVOTO (DLVOTO) has been infrequently identified in symptomatic patients without
      LV hypertrophy, and its pathophysiology is not well established. The aim of this
      study was to identify echocardiographic abnormalities that might explain the
      dynamic development of systolic anterior motion, mitral-septal contact, and LVOTO
      in these patients. METHODS: Patients with DLVOTO and normal wall thickness were
      compared with 20 age-matched and gender-matched controls with normal stress
      echocardiographic findings. Two other groups were also compared: patients with
      DLVOTO and mild segmental hypertrophy (segmental wall thickness <=15 mm) and
      patients with normal left ventricles but DLVOTO after dobutamine stress. RESULTS:
      Six symptomatic patients were identified (mean age, 48 +/- 9 years; range, 37-60
      years; five men) with normal wall thickness who developed DLVOTO after exercise
      during a 6-year period. Five had been hospitalized for cardiac symptoms. The mean
      postexercise LV outflow tract gradient caused by systolic anterior motion mitral
      septal contact was 107 +/- 55 mm Hg (range, 64-200 mm Hg). All patients had
      echocardiographic LV wall thicknesses in the normal range (<=12 mm). Structural
      abnormalities of the mitral valve were identified in all six patients. These were
      elongated posterior leaflets (2.0 vs 1.5 cm, P < .0005), elongated anterior
      leaflets (3.2 vs 2.6 cm, P = .015), increased protrusion height of the mitral
      valve beyond the mitral annular plane (2.6 vs 0.6 cm, P < .00001), and residual
      protruding portions of the mitral valve leaflets (0.85 vs 0.24 cm, P < .005).
      There was anterior positioning of the papillary muscles in the LV cavity, with a
      greater distance from the plane of the papillary muscles to the posterior wall
      (1.8 vs 1.3 cm, P = .03). In two patients, potentially provoking medications were
      stopped; two patients received beta-blockers, with reductions of angina. Medium
      term prognosis was good; no patient had died after 3.5 years. The mitral valve
      abnormalities in the 10 patients with DLVOTO and mild segmental hypertrophy were
      qualitatively and quantitatively very similar to those in patients with DLVOTO
      without hypertrophy. In contrast, the valves of patients with dobutamine stress
      DLVOTO were not elongated, but 50% had residual mitral leaflets that protruded
      past the coaptation point by >=5 mm. CONCLUSIONS: DLVOTO after exercise can occur
      in the absence of LV hypertrophy and may be associated with high gradients and
      cardiac symptoms. Elongated, redundant mitral valve leaflets with anterior
      position of the papillary muscles appear to cause the postexercise obstruction.

PMID- 23534984
TI  - Structure analysis of the La Guajira-Colombia population: a genetic, demographic
      and genealogical overview.
AB  - BACKGROUND: This study examined whether cultural factors, as compared to
      geographical distance, have produced a population sub-structure among different
      groups from the La Guajira population (Amerindian Wayuu and other resident
      groups) that co-exist within the same region. AIMS: The aims of this study were
      to analyse this population to discover whether cultural barriers result in the
      sub-structure, to evaluate whether there is a genetic drift effect and to
      describe migration dynamics using a genetic, genealogical and demographic
      approach. SUBJECTS: This study examined a sample of 290 individuals who were
      grouped based on a genealogical criterion to distinguish between native
      individuals and migrants. MATERIALS AND METHODS: Using demographic information,
      the age and gender structure of the population and genetic drift estimators were
      analysed. Using 15 autosomal microsatellites, heterozygosity, Hardy-Weinberg
      equilibrium (HWE), inbreeding, sub-structure, recent migration rate and genetic
      relationships were also evaluated using a Principal Component analysis (PCA)
      using reference populations. RESULTS: La Guajira is a young population that is
      growing and exposed to a moderate effect of genetic drift (Neme 11.903). The
      Wayuu are highly diverse (Ho 0.727) and different from other groups, with the
      exception of Wayuu-Guajiro. This trend was also observed in other Amerindian
      populations. CONCLUSION: This study found a high level of admixture and gene flow
      within the Wayuu population despite cultural differences. Thus, although the
      Wayuu population differs from other population groups, it is not an isolated
      population.

PMID- 23534986
TI  - Effect of light-induced conical intersection on the photodissociation dynamics of
      the D2(+) molecule.
AB  - It is known that conical intersections (CIs) can be induced by laser light even
      in diatomics. In the close vicinity of these laser-induced CIs (LICIs) the
      nonadiabatic effects are infinitely strong, as is the case for naturally
      appearing CIs in field-free polyatomics. In the present work we study the
      photodissociation dynamics of the D(2)(+) molecule in an intense laser field to
      investigate the role of the LICI. Specifically, the kinetic energy release (KER)
      and the angular distribution of the photodissociation products are calculated
      with and without LICI for different initial conditions and for different values
      of the laser parameters. To do so, both one- and two-dimensional calculations
      were performed. In the first model the molecules were rotationally frozen,
      whereas in the latter one, the molecular rotation is included as a full
      additional dynamic variable. The results obtained undoubtedly demonstrate the
      strong impact of the coupling of the rotation to the vibrational and electronic
      motions and hence of the LICI on the dissociation dynamics of the D(2)(+)
      molecule.

PMID- 23534985
TI  - Facile and stabile linkages through tyrosine: bioconjugation strategies with the
      tyrosine-click reaction.
AB  - The scope, chemoselectivity, and utility of the click-like tyrosine labeling
      reaction with 4-phenyl-3H-1,2,4-triazoline-3,5(4H)-diones (PTADs) is reported. To
      study the utility and chemoselectivity of PTAD derivatives in peptide and protein
      chemistry, we synthesized PTAD derivatives possessing azide, alkyne, and ketone
      groups and studied their reactions with amino acid derivatives and peptides of
      increasing complexity. With proteins we studied the compatibility of the tyrosine
      click reaction with cysteine and lysine-targeted labeling approaches and
      demonstrate that chemoselective trifunctionalization of proteins is readily
      achieved. In particular cases, we noted that PTAD decomposition resulted in
      formation of a putative isocyanate byproduct that was promiscuous in labeling.
      This side reaction product, however, was readily scavenged by the addition of a
      small amount of 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) to the reaction
      medium. To study the potential of the tyrosine click reaction to introduce
      poly(ethylene glycol) chains onto proteins (PEGylation), we demonstrate that this
      novel reagent provides for the selective PEGylation of chymotrypsinogen, whereas
      traditional succinimide-based PEGylation targeting lysine residues provided a
      more diverse range of PEGylated products. Finally, we applied the tyrosine click
      reaction to create a novel antibody-drug conjugate. For this purpose, we
      synthesized a PTAD derivative linked to the HIV entry inhibitor aplaviroc.
      Labeling of the antibody trastuzumab with this reagent provided a labeled
      antibody conjugate that demonstrated potent HIV-1 neutralization activity
      demonstrating the potential of this reaction in creating protein conjugates with
      small molecules. The tyrosine click linkage demonstrated stability to extremes of
      pH, temperature, and exposure to human blood plasma indicating that this linkage
      is significantly more robust than maleimide-type linkages that are commonly
      employed in bioconjugations. These studies support the broad utility of this
      reaction in the chemoselective modification of small molecules, peptides, and
      proteins under mild aqueous conditions over a broad pH range using a wide variety
      of biologically acceptable buffers such as phosphate buffered saline (PBS) and 2
      amino-2-hydroxymethyl-propane-1,3-diol (Tris) buffers as well as others and mixed
      buffered compositions.

PMID- 23534987
TI  - Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal
      injury through paracrine mechanisms.
AB  - Mesenchymal stem cells (MSCs) have been reported to preserve renal function in
      various models of acute kidney injury (AKI). Different routes were used to
      transplant MSCs but the role of cell transplantation routes in directing outcomes
      has been unknown. In the present study, we evaluated organ bio-distributions of
      transplanted MSCs, and correlated survival of transplanted cells with outcomes in
      mice with cisplatinum-induced AKI. We found that after intravenous
      administration, MSCs were largely localized in pulmonary capillaries and only a
      minute fraction of MSCs entered kidneys and the cells survived only transiently.
      Therefore, we also transplanted MSCs via intraperitoneal and renal subcapsular
      routes. Transplanted MSCs survived longer in peritoneal cavity and renal
      subcapsular space. Interestingly, when MSC transplantation was followed by
      cisplatinum-induced AKI, renal morphology and renal functions were better
      preserved, irrespective of the cell transplantation route. As transplanted MSCs
      did not migrate to kidneys from either peritoneal cavity or renal subcapsular
      space, this finding suggested that migration of cells was not required for the
      beneficial response. The possibility of indirect mechanisms was confirmed when
      administration of the conditioned medium from MSCs also protected renal tubular
      cells from cisplatinum-induced cytotoxicity. We identified presence of over forty
      regulatory cytokines in the conditioned medium obtained from MSCs. Since
      paracrine factors released by transplanted cells accounted for improvements, it
      appears that the route of cell transplantation is not critical for realizing
      benefits of cell therapy with MSCs in AKI. Studies of specific cytokines secreted
      by MSCs will help to obtain new therapeutic mechanisms for renal protection.

PMID- 23534988
TI  - Cost-utility analysis of nanoparticle albumin-bound paclitaxel versus paclitaxel
      in monotherapy in pretreated metastatic breast cancer in Spain.
AB  - AIM: The COSTABRAX study evaluated the cost-effectiveness of nanoparticle albumin
      bound paclitaxel (nab-paclitaxel) versus polyethylated castor oil-based standard
      paclitaxel (sb-paclitaxel) in the treatment of patients with previously treated
      metastatic breast cancer in Spain. MATERIALS & METHODS: Efficacy data were
      obtained from the CA012 trial (nab-paclitaxel administered every 3 weeks [q3w]
      and sb-paclitaxel q3w) and indirect comparison (sb-paclitaxel administered
      weekly), and were modeled to a time horizon of 5 years using a Markov model. The
      analysis was performed from the National Health Service perspective. Use of
      resources and key assumptions of the model were validated by a panel of 22 local
      oncologists. RESULTS: Compared with sb-paclitaxel q3w, nab-paclitaxel q3w was
      cost effective, with a cost per life year gained of ?11,088 and a cost per
      quality-adjusted life year of ?17,808. Compared with sb-paclitaxel administered
      weekly, it showed savings of ?711 per patient. CONCLUSION: The COSTABRAX study
      showed that nab-paclitaxel q3w is a cost-effective alternative compared with sb
      paclitaxel q3w and a cost-saving alternative to sb-paclitaxel administered weekly
      in Spain.

PMID- 23534989
TI  - Group analysis of self-organizing maps based on functional MRI using restricted
      Frechet means.
AB  - Studies of functional MRI data are increasingly concerned with the estimation of
      differences in spatio-temporal networks across groups of subjects or experimental
      conditions. Unsupervised clustering and independent component analysis (ICA) have
      been used to identify such spatio-temporal networks. While these approaches have
      been useful for estimating these networks at the subject-level, comparisons over
      groups or experimental conditions require further methodological development. In
      this paper, we tackle this problem by showing how self-organizing maps (SOMs) can
      be compared within a Frechean inferential framework. Here, we summarize the mean
      SOM in each group as a Frechet mean with respect to a metric on the space of
      SOMs. The advantage of this approach is twofold. Firstly, it allows the
      visualization of the mean SOM in each experimental condition. Secondly, this
      Frechean approach permits one to draw inference on group differences, using
      permutation of the group labels. We consider the use of different distance
      functions, and introduce one extension of the classical sum of minimum distance
      (SMD) between two SOMs, which take into account the spatial pattern of the fMRI
      data. The validity of these methods is illustrated on synthetic data. Through
      these simulations, we show that the two distance functions of interest behave as
      expected, in the sense that the ones capturing temporal and spatial aspects of
      the SOMs are more likely to reach significance under simulated scenarios
      characterized by temporal, spatial [and spatio-temporal] differences,
      respectively. In addition, a re-analysis of a classical experiment on visually
      triggered emotions demonstrates the usefulness of this methodology. In this
      study, the multivariate functional patterns typical of the subjects exposed to
      pleasant and unpleasant stimuli are found to be more similar than the ones of the
      subjects exposed to emotionally neutral stimuli. In this re-analysis, the group
      level SOM output units with the smallest sample Jaccard indices were compared
      with standard GLM group-specific z-score maps, and provided considerable levels
      of agreement. Taken together, these results indicate that our proposed methods
      can cast new light on existing data by adopting a global analytical perspective
      on functional MRI paradigms.

PMID- 23534990
TI  - Make your own kinds of cues: when children make more accurate inferences than
      adults.
AB  - In everyday decision making, we do not always have the luxury of using certain
      knowledge but often need to rely on cues, that is, pieces of information that can
      aid reasoning. We ask whether and under what circumstances children can focus on
      informative cues and make accurate inferences in real-world problems. We tested
      second-, third-, and fifth-grade children and young adults on two problems: which
      of two real cars is more expensive and which of two real cities has more
      inhabitants. We manipulated whether cues were given to the participants or the
      participants needed to generate their own cues. The main result was that when
      generating their own cues, younger children matched older children and young
      adults in accuracy or even outperformed them. On the other hand, when cues were
      given, children were less accurate than young adults. A possible explanation for
      this result is that children, on their own, tend to generate "perceptual" cues
      (e.g., "Which car is longer?") that are informative in the problems we studied.
      However, children are not able to recognize the most informative cues in a set
      that is given to them because they are not familiar with all cues (e.g., non
      perceptual cues such as which car has more horsepower).

PMID- 23534991
TI  - Lipase-catalyzed aza-Michael reaction on acrylate derivatives.
AB  - A methodology has been developed for an efficient and selective lipase-catalyzed
      aza-Michael reaction of various amines (primary and secondary) with a series of
      acrylates and alkylacrylates. Reaction parameters were tuned, and under the
      optimal conditions it was found that Pseudomonas stutzeri lipase and
      Chromobacterium viscosum lipase showed the highest selectivity for the aza
      Michael addition to substituted alkyl acrylates. For the first time also, some
      CLEAs were examined that showed a comparable or higher selectivity and yield than
      the free enzymes and other formulations.

PMID- 23534992
TI  - Cutaneous leukocytoclastic vasculitis due to erlotinib: just an adverse event or
      also a putative marker of drug efficacy?
AB  - Erlotinib is a targeted anticancer therapy with selective inhibitory activity for
      tyrosine kinase of the epidermal growth factor receptor (EGFR). Different skin
      reactions have been described linked to these drugs. There are no other reports
      about erlotinib-induced leukocytoclastic vasculitis (LV) in the erlotinib
      bevacizumab regimen for bone metastasis, from a relapsed hepatocellular carcinoma
      (HCC) in liver-transplanted patients. In our patient a dose reduction and then
      the suspension of erlotinib was required. After a 2 week withdrawal, the drug was
      re-challenged at a lower dose. The patient continued it without any skin
      recurrence, and resulted progression free for 16 months. Thus, we underline the
      possibility to avoid a permanent withdrawal of erlotinib and to rechallenge with
      it without any cutaneous toxicity, particularly in patients benefiting from this
      drug. Moreover, the median overall survival from the initial treatment of bone
      relapsed patients after liver transplant for HCC is found to be less than 5
      months, while our patient died 5 years later. This longer survival encourages
      further investigations to assess also whether LV, even if rare, might be used as
      a marker of antitumor efficacy of EGFR inhibitors.

PMID- 23534993
TI  - Improved tumor targeting by mild hyperthermia.

PMID- 23534994
TI  - Ovulatory follicle dysfunction in lactating dairy cows after treatment with
      Folltropin-V at the onset of luteolysis.
AB  - The objective was to examine growth of the ovulatory follicle after FSH
      (Folltropin-V; Bioniche Animal Health, Belleville, Ontario, Canada) was given at
      the onset of induced luteolysis during a synchronization of ovulation protocol.
      Using GnRH or hCG for inducing ovulation enabled assessing ovulatory follicle
      responsiveness to an endogenous versus exogenous surge of LH activity. At 8 to 10
      days after estrus (synchronized estrus = Day 0), lactating dairy cows received an
      Eazi-Breed CIDR (Pfizer Animal Health) plus 100 MUg GnRH. After 7 days,
      controlled internal drug release devices (CIDRs) were removed, cows were given
      500 MUg cloprostenol, and then randomly allocated to receive 80 mg Folltropin-V
      (FSH; N = 19) or 4 mL sterile saline (SAL; N = 16). After 49 hours, FSH and SAL
      cows were randomly allocated to receive 100 MUg GnRH or 3000 IU hCG. Five cows
      ovulated 30 to 42 hours (38.4 +/- 1.2 hours) after FSH treatment. In the
      remaining FSH (N = 14) or SAL (N = 16) cows, ovulatory follicle size was similar
      at CIDR removal (14.5 +/- 0.6 and 14.7 +/- 0.6 mm, respectively; P = 0.85) and
      when GnRH/hCG was given (16.6 +/- 0.6 and 17.7 +/- 0.6 mm, respectively; P =
      0.23). Estradiol-17beta concentrations were lower in FSH cows at 36 and 49 hours
      after CIDR removal (FSH by time interaction, P < 0.005). After GnRH or hCG
      treatment, four FSH cows failed to ovulate. In cows exhibiting ovulation, the
      last recorded size of the ovulatory follicle was not influenced by FSH (18.1 +/-
      0.9 and 17.5 +/- 0.6 mm for FSH and SAL, respectively; P = 0.59) or hormonal
      induction approach (18.4 +/- 0.9 and 17.2 +/- 0.7 mm for GnRH and hCG,
      respectively; P = 0.29). The interval from onset of luteolysis to ovulation and
      pharmaceutical induction to ovulation was shorter in FSH cows given GnRH (FSH by
      pharmaceutical inducer [GnRH vs. hCG] interaction; P = 0.01). Cows receiving GnRH
      had an LH surge; hCG-treated cows did not. Maximum LH concentrations were greater
      (P < 0.04) in SAL versus FSH cows after GnRH treatment (10.9 +/- 1.2 vs. 6.7 +/-
      1.4 ng/mL, respectively). In three FSH cows failing to ovulate after GnRH
      treatment, the maximum LH concentration was <4 ng/mL. When analyzed from GnRH
      treatment, average time to LH maximum concentration was similar (P = 0.50) to
      values obtained in cows receiving FSH and GnRH and SAL and GnRH (1.7 +/- 0.2 vs.
      1.9 +/- 0.1 hours, respectively). Interval to maximum hCG concentrations was
      shorter (P = 0.02) for cows receiving SAL versus FSH (8.0 +/- 0.8 and 10.0 +/-
      0.8 hours for SAL and FSH, respectively). Ovulatory dysfunction of this magnitude
      highlighted the lack of suitability of Folltropin-V at a dose of 80 mg at the
      time of induction of luteolysis in fixed timed AI protocols.

PMID- 23534995
TI  - Length of the follicular growing phase and oocyte competence in beef heifers.
AB  - We tested the hypotheses that extending the duration of follicular growth by
      superstimulation increases oocyte competence, and that FSH starvation at the end
      of superstimulatory treatment decreases oocyte competence. Heifers were randomly
      assigned to three groups: short FSH, FSH starvation, and long FSH (N = 8 per
      group). At 5 to 8 days after ovulation, follicle ablation was performed, and a
      progesterone-releasing device (CIDR) was placed intravaginally. Short FSH and FSH
      starvation groups were given eight doses of FSH im at 12-hour intervals, and the
      long FSH group was given 14 doses. PGF2alpha was administered twice (12 hours
      apart) and the CIDR was removed on Day 3 (Day 0 = wave emergence) in the short
      FSH group, and on Day 6 in the other two groups. Heifers were given LH 24 hours
      after CIDR removal and cumulus-oocyte complexes (COC) were collected 24 hours
      later. The COC were matured in vitro for 6 hours and fertilized in vitro; embryos
      were cultured for 10 days. A greater number of follicles >=9 mm were detected in
      the long FSH group than in the FSH starvation and short FSH groups (25.4 +/- 5.3,
      11.0 +/- 2.1, 10.6 +/- 2.3, respectively; P < 0.03). A greater proportion of
      expanded COC were collected from the long FSH than from the FSH starvation group
      (P < 0.001), and the short FSH group was intermediate (93%, 54%, and 74%,
      respectively). The FSH starvation group had a greater proportion of poor quality
      oocytes than the short and long FSH groups (70%, 45%, and 33%, respectively; P <
      0.001) and cleavage rate was lower (22%, 54%, and 56%, respectively; P = 0.003).
      The proportion of oocytes that developed into embryos (morulae and blastocysts on
      Day 9 after IVF) was also lower in the FSH starvation group than in the short and
      long FSH groups, (5% vs. 25% and 37%; P = 0.04); the latter two groups did not
      differ. The long FSH treatment resulted in 2.5 and 3.4 times more transferable
      embryos per animal (morulae and blastocysts) at Day 9 after IVF than the short
      FSH and FSH starvation groups (5.6, 2.5, and 1.7 embryos per heifer respectively;
      P = 0.04). In conclusion, extending the standard superstimulation protocol by 3
      days enhanced the ovarian response to FSH treatment, and a period of FSH
      starvation after superstimulatory treatment compromised oocyte quality and the
      fertilization process.

PMID- 23534996
TI  - Progesterone regulation of Na/K-ATPase beta1 subunit expression in the mouse
      uterus during the peri-implantation period.
AB  - Luminal closure and embryo apposition are essential for blastocyst attachment
      during early pregnancy. In our preliminary microarray results (unpublished data),
      sodium-potassium adenosine triphosphatase (Na/K-ATPase) beta1 (Atp1b1) was highly
      expressed in mouse uterus on Days 3 and 4 of pregnancy. However, expression and
      regulation of Atp1b1 in the mammalian uterus during early pregnancy are unknown.
      Using in situ hybridization, a strong level of Atp1b1 mRNA was detected in
      luminal epithelial cells on Days 3 and 4 of pregnancy (Day 1 = day of vaginal
      plug). The expression pattern of FXYD domain-containing ion transport regulator 4
      (Fxyd4) was similar to that of Atp1b1. Real-time reverse transcription polymerase
      chain reaction confirmed the high expression level of Atp1b1 mRNA. Compared with
      Day 1, the mRNA level of Atp1b1 on Days 3 and 4 increased by 3.5 +/- 0.5 and 4.5
      +/- 0.5 fold, respectively. When the embryo invaded through epithelial cells into
      the maternal stromal compartment on day 5, Atp1b1 expression decreased to a basal
      level. Progesterone stimulated Atp1b1 expression by 2.8 +/- 1 fold compared with
      oil in ovariectomized mice at 24 hours after treatment. Expression of Atp1b1 was
      further upregulated to 4 +/- 0.4 fold by estrogen and progesterone. Based on time
      course study, progesterone rapidly induced Atp1b1 expression at 6 and 12 hours
      (13.7 +/- 0.5 and 16.6 +/- 1.4, respectively); furthermore, this upregulation was
      blocked by RU486 (progesterone receptor antagonist). Transcription activity of
      the Atp1b1 promoter was (Day 1 = day of vaginal plug) stimulated by
      CCAAT/enhancer binding protein beta (Cebpb). In conclusion, Atp1b1 was highly
      expressed in luminal epithelium during peri-implantation and upregulated by
      progesterone.

PMID- 23534997
TI  - Dynamics of intracellular phospholipid membrane organization during oocyte
      maturation and successful vitrification of immature oocytes retrieved by ovum
      pick-up in cattle.
AB  - The objective was to determine if immature bovine oocytes with cumulus cells at
      the germinal vesicle (GV) stage could be vitrified by aluminum sheets (AS; pieces
      of sheet-like aluminum foil). Cleavage rates in fertilized oocytes previously
      vitrified by the AS procedure were higher than those vitrified by a nylon-mesh
      holder (NM) procedure (89.3 +/- 2.1% vs. 65.0 +/- 3.7%). Cleaved embryos derived
      from the AS but not from the NM procedures developed to blastocysts. Furthermore,
      to investigate the effects of vitrifying GV oocytes on cytoplasmic structure and
      on the ability to undergo cytoplasmic changes, the intracellular phospholipid
      membrane (IM) was stained with the lipophilic fluorescent dye, 3,3'
      dioctadecyloxa-carbocyanine perchlorate. After vitrification by AS, the IM
      remained intact relative to that of oocytes vitrified by NM. During in vitro
      maturation, reorganization of the IM was also undamaged in oocytes vitrified by
      AS before oocyte maturation, and the IM within oocytes vitrified by the NM
      procedure was evidently impaired. Finally, vitrification (AS) was used for GV
      oocytes collected using the ovum pick-up method. A bull calf was born after in
      vitro production and subsequent embryo transfer. The vitrification techniques
      described herein should facilitate generation of viable in vitro production
      bovine blastocysts using oocytes recovered using the ovum pick-up method.

PMID- 23534998
TI  - Heavy metal content in ash of energy crops growing in sewage-contaminated natural
      wetlands: potential applications in agriculture and forestry?
AB  - One of the greatest current challenges is to find cost-effective and eco-friendly
      solutions to the ever increasing needs of modern society. Some plant species are
      suitable for a multitude of biotechnological applications such as bioenergy
      production and phytoremediation. A sustainable practice is to use energy crops to
      clean up polluted lands or to treat wastewater in constructed wetlands without
      claiming further arable land for biofuel production. However, the disposal of
      combustion by-products may add significant costs to the whole process, especially
      when it deals with toxic waste. This study aimed to investigate the possibility
      of recycling ash from energy biomass as a fertilizer for agriculture and
      forestry. In particular, the concentrations of Cd, Cr, Cu, Mn, Pb and Zn were
      analyzed in the plant tissues and corresponding ash of the grasses Phragmites
      australis and Arundo donax, collected in an urban stream affected by domestic
      sewage. Results showed that the metal concentration in ash is 1.5-3 times as high
      as the values in plant tissues. However, metal enriched ash showed much lower
      element concentrations than the legal limits for ash reutilization in agriculture
      and forestry. This study found that biomass ash from constructed wetlands may be
      considered as a potential fertilizer rather than hazardous waste. Energy from
      biomass can be a really sustainable and clean option not only through the
      reduction of greenhouse gas emissions, but also through ash recycling for
      beneficial purposes, thus minimizing the negative impacts of disposal.

PMID- 23535000
TI  - Phenanthro[9,10-d]imidazole-quinoline boron difluoride dyes with solid-state red
      fluorescence.
AB  - A new family of boron difluoride-rigidified dyes, phenanthro[9,10-d]imidazole
      quinoline boron difluoride (PQBD), with solid-state fluorescence has been
      designed and synthesized. The novel series of PQBD are advantageous over the
      typical boron difluoride-rigidified dyes such as BODIPYs in terms of large Stokes
      shift and red fluorescence in the solid state.

PMID- 23534999
TI  - Life-cycle assessment of typical Portuguese cork oak woodlands.
AB  - Cork forest systems are responsible for making an important economic contribution
      to the Mediterranean region, especially Portugal where the cork oak woodlands or
      montados contain about 32% of the world's area. The environmental profile derived
      from reproduction cork production and extraction in two Portuguese regions (Tagus
      valley and Alentejo) representative of the Portuguese sector were assessed in
      detail using the Life-Cycle Assessment (LCA) methodology from a cradle-to-gate
      perspective. The production line was divided into four stages considering all the
      processes involved: stand establishment, stand management, cork stripping and
      field recovery. According to the environmental results, there were remarkable
      differences between the two production scenarios mainly due to the intensity and
      repetition of forest activities even though the cork yield was reported to be the
      same. The management system in the Alentejo region presented the worse
      environmental profile in almost all the impact categories under assessment,
      mainly due to the shorter cycle duration of the mechanical cleaning and pruning
      processes. Cork stripping was identified in both scenarios as the production
      stage with the highest contribution to the environmental profile due to the
      cleaning and pruning processes. A sensitivity assessment concerning the cork
      yield was performed since the average production yields in the Portuguese
      montados are lower than the ones used in this study. Thus, if the cork yield is
      reduced, the environmental profile in both scenarios gets worse since almost all
      the forest activities involved are the same.

PMID- 23535001
TI  - Congenital ulcer of the buttock.
AB  - We present the case of a congenital, deep ulcer of the buttock in an otherwise
      healthy newborn girl. Histopathology excluded any specific cause of ulceration.
      The ulcer healed spontaneously at 4 weeks of age, leaving a scar. Because the
      patient also had symmetrical pits on her knees and because the ulcer was located
      in an area typically affected by dimples, we interpret this unique manifestation
      as a congenital defect in the spectrum of congenital dimples. 

PMID- 23535002
TI  - Prediction of alpaca fibre quality by near-infrared reflectance spectroscopy.
AB  - Rapid and efficient methods to evaluate variables associated with fibre quality
      are essential in animal breeding programs and fibre trade. Near-infrared
      reflectance spectroscopy (NIRS) combined with multivariate analysis was evaluated
      to predict textile quality attributes of alpaca fibre. Raw samples of fibres
      taken from male and female Huacaya alpacas (n = 291) of different ages and
      colours were scanned and their visible-near-infrared (NIR; 400 to 2500 nm)
      reflectance spectra were collected and analysed. Reference analysis of the
      samples included mean fibre diameter (MFD), standard deviation of fibre diameter
      (SDFD), coefficient of variation of fibre diameter (CVFD), mean fibre curvature
      (MFC), standard deviation of fibre curvature (SDFC), comfort factor (CF),
      spinning fineness (SF) and staple length (SL). Patterns of spectral variation
      (loadings) were explored by principal component analysis (PCA), where the first
      four PC's explained 99.97% and the first PC alone 95.58% of spectral variability.
      Calibration models were developed by modified partial least squares regression,
      testing different mathematical treatments (derivative order, subtraction gap,
      smoothing segment) of the spectra, with or without applying spectral correction
      algorithms (standard normal variate and detrend). Equations were selected through
      one-out cross-validation according to the proportion of explained variance (R
      2CV), root mean square error in cross-validation (RMSECV) and the residual
      predictive deviation (RPD), which relates the standard deviation of the reference
      data to RMSECV. The best calibration models were accomplished when using the NIR
      region (1100 to 2500 nm) for the prediction of MFD and SF, with R 2CV = 0.90 and
      0.87; RMSECV = 1.01 and 1.08 MUm and RPD = 3.13 and 2.73, respectively. Models
      for SDFD, CVFD, MFC, SDFC, CF and SL had lower predictive quality with R 2CV <
      0.65 and RPD < 1.5. External validation performed for MFD and SF on 91 samples
      was slightly poorer than cross-validation, with R 2 of 0.86 and 0.82, and
      standard error of prediction of 1.21 and 1.33 MUm, for MFD and SF, respectively.
      It is concluded that NIRS can be used as an effective technique to select alpacas
      according to some important textile quality traits such as MFD and SF.

PMID- 23535004
TI  - Exploration of "food addiction" in overweight and obese treatment-seeking adults.
AB  - There is growing interest in conceptualizing obesity as a "food addiction." The
      current study investigated the prevalence and correlates of "food addiction"
      (FA), as defined by the Yale Food Addiction Scale (YFAS) in 178 (133 F, 45M)
      persons seeking weight loss treatment. Participants had a mean age of 51.2+/
      11.7years and a body mass index of 36.1+/-4.8kg/m(2). Fifteen percent of
      individuals met the YFAS proposed diagnostic criteria for FA. Those who met
      criteria for FA reported significantly greater depressive symptomatology. There
      were no differences in BMI, age, race, or gender between participants with and
      without FA. Among those not meeting criteria, 35% reported 3 or more symptoms in
      the absence of self-reported clinical distress or impairment. YFAS symptom count
      was also significantly correlated with depressive symptoms. These findings
      suggest that 15% of adults presenting for weight loss treatment meet YFAS
      criteria for FA. The clinical significance of this classification is unknown and
      needs to be validated in prospective studies.

PMID- 23535005
TI  - What size tube doctor? Bigger may be better--at least for weaning.

PMID- 23535006
TI  - Dermatofibrosarcoma protuberans on the right neck with superior vena cava
      syndrome: case report and literature review.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon dermal soft tissue tumour
      of intermediate malignancy. A 44-year-old man presented to the hospital with a
      large lesion on the right upper chest and neck. Despite eight previous surgical
      excisions, the tumour had continued to recur. Contrast-enhanced computed
      tomography showed recurrence of the tumour, associated with superior vena cava
      (SVC) syndrome. He declined radical surgical resection of the recurrent tumour,
      which may have required right upper limb amputation. Targeted therapy with
      sunitinib malate was therefore introduced. This case demonstrates the recurrent
      nature of DFSP and the association of this lesion on the upper chest/neck with
      SVC syndrome. Primary wide radical resection is essential for better local
      control and to avoid the development of SVC syndrome.

PMID- 23535007
TI  - Efficacy of anti-inflammatory drugs in third molar surgery: a randomized clinical
      trial.
AB  - This was a double-blind randomized clinical trial to assess the effect of
      different pharmacological regimens on the level of prostaglandin E2 (PGE2) in
      urine and saliva, and to correlate the findings to the clinical course after
      removal of impacted lower third molars. Eighty patients were randomly divided
      into four groups: group 1 received placebo; group 2 received preoperative
      ibuprofen, which was continued for a week; group 3 received intraoperative
      dexamethasone; and group 4 received preoperative ibuprofen, which was continued
      for a week, in addition to intraoperative dexamethasone. Saliva and urine samples
      were taken at scheduled intervals. Patients receiving ibuprofen fared
      significantly better in most parameters. A single dose of dexamethasone alone had
      a potent but transient beneficial effect when compared to the results with
      ibuprofen, which showed significant improvement in both subjective and objective
      parameters. Use of a single dose of intravenous steroids perioperatively helped
      reduce untoward sequelae, although to a lesser degree and for a shorter duration
      than continuous ibuprofen. Combining ibuprofen with perioperative dexamethasone
      added some benefit in some of the measured parameters, but without a
      statistically significant advantage over using ibuprofen only.

PMID- 23535008
TI  - Growth rate of late passage sarcoma cells is independent of epigenetic events but
      dependent on the amount of chromosomal aberrations.
AB  - Soft tissue sarcomas (STS) are characterized by co-participation of several
      epigenetic and genetic events during tumorigenesis. Having bypassed cellular
      senescence barriers during oncogenic transformation, the factors further
      affecting growth rate of STS cells remain poorly understood. Therefore, we
      investigated the role of gene silencing (DNA promoter methylation of LINE-1,
      PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their
      contribution to the proliferation rate and migratory potential that underlies
      "initial" and "final" passage sarcoma cells. Three different cell lines were
      used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and
      HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS
      cells was not associated with significant differences in methylation (LINE-1,
      PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of
      chromosomal aberrations. Collectively, our data demonstrate that these fairly
      differentiated/advanced cancer cell lines have still the potential to gain an
      additional spontaneous growth benefit without external influences and that
      maintenance of increased proliferative potential towards longevity of STS cells
      (having crossed senescence barriers) may be independent of overt epigenetic
      alterations. 

PMID- 23535009
TI  - The Par3/Par6/aPKC complex and epithelial cell polarity.
AB  - Apical-basal polarity is the basic organizing principle of epithelial cells, and
      endows epithelial cells to function as defensive barriers and as mediators of
      vectorial transport of nutrients in and out of organisms. Apical-basal polarity
      is controlled by a number of conserved polarity factors that regulate
      cytoskeletal organizations, asymmetric distributions of cellular components, and
      directional transports across cells. Polarity factors often occupy specific
      membrane regions in response to the adhesion forces generated by cell-cell and
      cell-extracellular matrix interactions. Both internal polarity factors and the
      external extracellular matrices play fundamental roles in epithelial cell
      polarity establishment and maintenance. This review focuses on recent
      developments of the Par3/Par6/aPKC complex and its interacting proteins in
      epithelial cell polarity.

PMID- 23535011
TI  - Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children.
AB  - OBJECTIVE: To evaluate the clinical features in a large cohort of pediatric
      patients with genetically confirmed hereditary hemorrhagic telangiectasia (HHT)
      and to identify possible predictors of arteriovenous malformation (AVM) onset or
      clinical significance. STUDY DESIGN: Prospective cross-sectional survey of all
      children subjected to screening for AVMs in the multidisciplinary HHT center. All
      patients proved to be carriers of endoglin mutations or activin A receptor type
      II-like kinase 1 mutations, defined as HHT1 and HHT2, respectively. A full
      clinical-radiological protocol for AVM detection was adopted, independent from
      presence or absence of AVM-related symptoms. RESULTS: Forty-four children (mean
      age, 10.3 years; range, 1-18) were subjected to a comprehensive clinical
      radiologic evaluation. This investigation disclosed cerebrovascular malformations
      in 7 of 44 cases, pulmonary AVMs in 20 of 44 cases, and liver AVMs in 23 of 44
      cases. Large visceral AVMs were found in 12 of 44 children and were significantly
      more frequent in patients with HHT1. Only large AVMs were associated with
      symptoms and complications. CONCLUSIONS: Children with HHT have a high prevalence
      of AVMs; therefore, an appropriate clinical and radiological screening protocol
      is advisable. Large AVMs can be associated with complications in childhood,
      whereas small AVMs probably have no clinical risk.

PMID- 23535010
TI  - Clinical and molecular spectrum of renal malformations in Kabuki syndrome.
AB  - OBJECTIVE: To determine the frequency and types of renal malformations, and to
      evaluate renal function in a cohort of patients with Kabuki syndrome (KS). STUDY
      DESIGN: Renal ultrasound scans and plasma creatinine measurements were collected
      from a French cohort of 94 patients with genotyped KS. Renal function was
      evaluated based on the estimated glomerular filtration rate. A genotype-phenotype
      study was conducted for renal and urinary tract malformations. RESULTS: Renal
      malformations were present in 22% of cases, and urinary tract anomalies were
      present in 15%. Renal malformations were observed in 28% of the MLL2 mutation
      positive group and in 0% of the MLL2 mutation-negative group (P = .015). No
      correlation was found between the presence or absence of renal or urinary tract
      malformations and the location or type of MLL2 mutation. Renal function was
      normal except for 1 patient with a MLL2 mutation diagnosed in the first days of
      life and severe renal disease due to unilateral renal agenesia and controlateral
      severe hypoplasia that progressed to the terminal stage at age 2 years.
      CONCLUSION: Our study emphasizes the need for ultrasound and renal function
      screening in children diagnosed with KS.

PMID- 23535013
TI  - Chemical and biological assessment of two offshore drilling sites in the Alaskan
      Arctic.
AB  - A retrospective chemical and biological study was carried out in Camden Bay,
      Alaskan Beaufort Sea, where single exploratory oil wells were drilled at two
      sites more than two decades ago. Barium from discharged drilling mud was present
      in sediments at concentrations as high as 14%, ~200 times above background, with
      significantly higher concentrations of Ba, but not other metals, within 250 m of
      the drilling site versus reference stations. Elevated concentrations of Cr, Cu,
      Hg and Pb were found only at two stations within 25 m of one drilling site.
      Concentrations of total polycyclic aromatic hydrocarbons (TPAH) were not
      significantly different at reference versus drilling-site stations; however, TPAH
      were elevated in Ba-rich layers from naturally occurring perylene in ancient
      formation cuttings. Infaunal biomass and species abundance were not significantly
      different at reference versus drilling-site stations; infauna were less diverse
      at drilling-site stations. Our assessment showed that discharges from single
      wells within large areas caused minimal long-term, adverse impacts to the benthic
      ecosystem.

PMID- 23535012
TI  - Pubertal height velocity and associations with prepubertal and adult heights in
      cystic fibrosis.
AB  - OBJECTIVES: To test the hypothesis that pubertal peak height velocity (PHV) in
      cystic fibrosis (CF) has improved and is influenced by prepubertal growth and
      genetic potential. STUDY DESIGN: PHV from 1862 children born in 1984-87 and
      documented in the 1986-2008 US CF Foundation Registry was determined by
      statistical modeling and classified into normal, delayed (2-SD > average age),
      attenuated (magnitude <5th percentile), or both delayed and attenuated (D&A).
      Genetic potential for height was estimated by parental stature. RESULTS: PHV
      averaged 8.4 cm/year at age 14.0 years in boys and 7.0 cm/year at age 12.1 years
      in girls, ~6-month delay and ~15% reduction compared with healthy children. PHV
      was normal in 60%, delayed in 9%, attenuated in 21%, and D&A in 5%. Patients with
      delayed PHV reached similar adult height percentile (boys: 34th, girls: 46th) to
      those with normal PHV (boys: 33rd, girls: 34th); both were significantly taller
      than the attenuated (boys: 11th, girls: 19th) and D&A PHV subgroups (boys: 8th,
      girls: 14th). Pancreatic-sufficient patients had taller prepubertal and adult
      heights but similar PHV compared with pancreatic-insufficient or meconium ileus
      patients. Adjusting for genetic potential reduced adult height percentiles more
      in boys (from 25th to 16th) than girls (from 28th to 24th). Height at age 7
      years, PHV age and magnitude, and parental stature significantly predicted adult
      height. CONCLUSIONS: Pubertal PHV has improved in children with CF born after mid
      1980s compared with older cohorts but remains below normal. Suboptimal
      prepubertal and pubertal growth led to adult height below genetic potential in
      CF.

PMID- 23535014
TI  - A spatially explicit risk approach to support marine spatial planning in the
      German EEZ.
AB  - An ecosystem approach to marine spatial planning (MSP) promotes sustainable
      development by organizing human activities in a geo-spatial and temporal context.
      (1) This study develops and tests a spatially explicit risk assessment to support
      MSP. Using the German exclusive economic zone (EEZ) of the North Sea as a case
      study area, current and future spatial management scenarios are assessed. (2)
      Different tools are linked in order to carry out a comprehensive spatial risk
      assessment of current and future spatial management scenarios for ecologic and
      economic ecosystem components, i.e. Pleuronectes platessa nursery grounds. With
      the identification of key inputs and outputs the suitability of each tool is
      tested. (3) Here, the procedure as well as the main findings of the spatially
      explicit risk approach are summarised to demonstrate the applicability of the
      framework and the need for an ecosystem approach to risk management techniques
      using geo-spatial tools.

PMID- 23535015
TI  - Impact of laboratory exposure to light Arabian crude oil, dispersed oil and
      dispersant on the gills of the juvenile brown spotted grouper (Epinephelus
      chlorostigma): a histopathological study.
AB  - The present study investigated the impact of subchronic exposure of the water
      accommodated fraction (WAF) of light Arabian crude oil, dispersed oil and
      dispersant on the gills of the juvenile brown spotted grouper (Epinephelus
      chlorostigma), observing several histopathological lesions at different time
      points and different concentrations. Significant alterations, compared to the
      control groups (p < 0.05), in four health categories (circulatory, proliferative,
      degenerative and inflammatory) were identified. Evaluations of histopathological
      lesions in gill tissue were carried out following 3, 6, 9, 12, 15, 18 and 21 days
      of exposure. The main lesions observed were circulatory (lamellar aneurysms,
      vasodilatation and hemorrhage), degenerative (edema, lifting of lamellar and
      filamentary epithelium and epithelium necrosis), proliferative (hypertrophy and
      hyperplasia of epithelial, mucous and chloride cells, fusion of adjacent
      lamellae), and inflammatory (lymphocytic infiltration). These results provide a
      tool for evaluating reclamation initiatives, such as the use of dispersants, and
      lead to better risk evaluations and environmental health in natural and reclaimed
      systems.

PMID- 23535016
TI  - Biomarkers in mangrove root crab Goniopsis cruentata for evaluating quality of
      tropical estuaries.
AB  - The present study reports the use of biomarkers analyzes in mangrove root crab
      Goniopsis cruentata tissues to assess the environmental quality of two tropical
      estuarine areas. Animals from Ceara River estuary presented inhibition of ChE and
      GST enzymatic activities and higher rates of DNA damage with respect to those
      sampled in a pristine environment. G. cruentata appears to represent a proper
      species to monitor the quality of tropical estuaries. Since Ceara River is a
      legally protected area, this survey highlight the needs to implement actions to
      control pollution loads and improve the protection of natural ecosystems and
      resources.

PMID- 23535017
TI  - Phylogenetic relationships among genera of the Periclimenes complex (Crustacea:
      Decapoda: Pontoniinae) based on mitochondrial and nuclear DNA.
AB  - The genus Periclimenes Costa, 1844 is the most species-rich genus in the
      subfamily Pontoniinae. Recent studies have suggested that it might be a
      polyphyletic taxon and could be further subdivided. In this study, three protein
      coding nuclear genes and one mitochondrial ribosomal gene were used to analyze
      the phylogenetic relationships among the genera of the Periclimenes complex,
      includes the genus Periclimenes and 15 related genera, viz. Ancylomenes,
      Brucecaris, Crinotonia, Cuapetes, Harpiliopsis, Harpilius, Laomenes,
      Leptomenaeus, Manipontonia, Palaemonella, Periclimenella, Philarius, Phycomenes,
      Unguicaris and Vir. Based on both independent and combined data analyses, the
      results support that the genus Periclimenes is a polyphyletic group. Furthermore,
      the studied Periclimenes species could be divided into several independent
      groups, and the taxonomic status of P. commensalis, P. brevicarpalis and P.
      digitalis may need to be reconsidered. Besides, the majority of the related
      genera of Periclimenes are suggested to be monophyletic. Our analyses also reveal
      that these genera approximately form two main clades, despite some deep
      relationships are still obscure.

PMID- 23535018
TI  - Patients who call emergency ambulances for primary care problems: a qualitative
      study of the decision-making process.
AB  - BACKGROUND: Telephone calls for emergency ambulances are rising annually,
      increasing the pressure on ambulance resources for clinical problems that could
      often be appropriately managed in primary care. OBJECTIVE: To explore and
      understand patient and carer decision making around calling an ambulance for
      primary care-appropriate health problems. METHODS: Semistructured interviews were
      conducted with patients and carers who had called an ambulance for a primary care
      appropriate problem. Participants were identified using a purposive sampling
      method by a non-participating research clinician attending '999' ambulance calls.
      A thematic analysis of interview transcripts was undertaken. RESULTS: A
      superordinate theme, patient and carer anxiety in urgent-care decision making,
      and four subthemes were explored: perceptions of ambulance-based urgent care;
      contrasting perceptions of community-based urgent care; influence of previous
      urgent care experiences in decision making; and interpersonal factors in lay
      assessment and management of medical risk and subsequent decision making.
      CONCLUSIONS: Many calls are based on fundamental misconceptions about the types
      of treatment other urgent-care avenues can provide, which may be amenable to
      educational intervention. This is particularly relevant for patients with chronic
      conditions with frequent exacerbations. Callers who have care responsibilities
      often default to the most immediate response available, with decision making
      driven by a lower tolerance of perceived risk. There may be a greater role for
      more detailed triage in these cases, and closer working between ambulance
      responses and urgent primary care, as a perceived or actual distance between
      these two service sectors may be influencing patient decision making on urgent
      care.

PMID- 23535019
TI  - Do partition coefficients (liphophilicity/hydrophilicity) predict effects of
      occlusion on percutaneous penetration in vitro: a retrospective review.
AB  - CONTEXT: Skin occlusion influences percutaneous penetration by limiting penetrant
      evaporation, but also through impeding loss of water from skin and increasing the
      hydration state of the stratum corneum, thus dramatically altering the
      physiological nature of the stratum corneum. In general, occlusion is widely
      utilized to enhance penetration of applied drugs in clinical practice; however,
      occlusion does not increase the percutaneous absorption of all chemicals.
      OBJECTIVE: We focus on what effect occlusion has on the in vitro percutaneous
      absorption of compounds of varying lipophilicities/hydrophilicities. METHODS:
      Studies and prior reviews of the effects of occlusion on the in vitro
      percutaneous penetration of penetrants of varying
      lipophilicities/hydrophilicities were identified in the MEDLINE, PubMED, Embase
      and Science Citation Index databases using the terms occlusive, occluded,
      occlusion, in vitro, skin and percutaneous absorption/penetration to generate as
      broad of a search as possible. From the results generated, abstracts were
      subsequently scrutinized to identify articles dealing primarily with in vitro
      models of the skin involving occlusion. Moreover, after the identification of
      relevant articles, their references were examined to find additional sources of
      information. RESULTS: After examining the research articles generated by the
      search results, five original research articles were obtained that used in vitro
      occlusion models and provided insight regarding the role of partition
      coefficients in predicting occlusion's effects on percutaneous penetration;
      articles that dealt with occlusion and percutaneous penetration but did not shed
      light on how the lipophilicity/hydrophilicity of a compound could affect
      occlusion efficacy were excluded. Some of the studies bolster the notion that
      occlusion-enhanced hydration of the stratum corneum increases the percutaneous
      absorption of lipophilic molecules more than hydrophilic molecules, which seems
      to confirm some in vivo studies. However, this effect was not consistent; many
      studies reviewed did not find that the penetrant's liphophilicity/hydrophilicity
      reliably predicted occlusion's effect on penetration. In these studies,
      lipophilic compounds did not demonstrate increased percutaneous absorption under
      occlusion. CONCLUSION: Thus, it does not seem that partition coefficients can
      reliably predict the effect of occlusion on percutaneous penetration in vitro.
      This suggests skin occlusion may be more complex than previously thought.

PMID- 23535020
TI  - Inhibitory effect of chaga mushroom extract on compound 48/80-induced
      anaphylactic shock and IgE production in mice.
AB  - Chaga mushrooms (Inonotus obliquus) are hypothesised to exhibit general immune
      potentiating, anti-inflammatory, and antitumor properties, but their anti
      allergic activities are not fully understood. Therefore, this study investigated
      whether a chaga mushroom extract (C-HE) might have anti-allergic activity. This
      activity was assessed through the levels of the IgE Ab produced in response to an
      allergen (OVA). The administration of C-HE prophylactically inhibited the
      systemic anaphylactic shock induced by compound 48/80 in mice. The oral
      administration of C-HE significantly reduced the total IgE levels in mice and
      slightly affected the production of IgG1. Furthermore, spleen cell cultures
      harvested from OVA-sensitised mice that had received C-HE orally showed a
      significant increase in Th1-derived responses (IFN-gamma production). Therefore,
      our results suggest that the chaga mushroom extract may be used as an anti
      allergic functional food.

PMID- 23535021
TI  - Effective stimulation of invariant natural killer T cells by oligomannose-coated
      liposomes.
AB  - vThe in vitro and in vivo response of invariant natural killer T (iNKT) cells to
      alpha-galactosylceramide (alphaGC)-containing oligomannose-coated liposomes
      (alphaGC-OMLs) was examined to determine whether selective delivery of alphaGC to
      dendritic cells (DCs) and subsequent activation of iNKT cells could be achieved.
      Splenocytes stimulated with alphaGC-OMLs produced higher levels of IFN-gamma
      compared to those stimulated with bare liposomes without an oligomannose coating
      (alphaGC-BLs). The ratio of IFN-gamma/IL-4 produced from alphaGC-OML-treated
      splenocytes was higher than those produced from alphaGC-BL- and soluble alphaGC
      treated cells. Depletion of CD3(+)-, DX5(+)- or CD11c(+)-cells from splenocytes
      almost completely abolished the alphaGC-OML-stimulated cytokine production,
      suggesting that both NKT cells and DCs were involved in the response to alphaGC
      OML stimulation. In addition, alphaGC-OMLs were incorporated into both splenic
      and bone marrow-derived DCs more effectively than alphaGC-BLs. iNKT cells
      stimulated with DCs with ingested alphaGC-OMLs produced much higher levels of IFN
      gamma than those stimulated with DCs containing alphaGC-BLs or soluble alphaGC.
      Systemic administration of alphaGC-OMLs led to modification of the kinetics of
      IFN-gamma production in vivo and also resulted in predominant production of IFN
      gamma from splenocytes over IL-4. In addition, iNKT cells proliferated and
      expanded upon in vivo activation of the cells with alphaGC-OMLs much more
      extensively than with alphaGC-BLs or soluble alphaGC. Collectively, our results
      suggest that alphaGC-OMLs can be used as a preferential delivery system for lipid
      antigens to DCs to activate iNKT cells in vivo and ex vivo.

PMID- 23535022
TI  - Synthesis of 6-alkyluridines from 6-cyanouridine via zinc(II) chloride-catalyzed
      nucleophilic substitution with alkyl Grignard reagents.
AB  - 6-Cyanouracil derivatives underwent a direct nucleophilic substitution reaction
      with alkyl Grignard reagents in the presence of zinc(II) chloride as a catalyst
      to form the corresponding 6-alkyluracils. This methodology is applicable to sugar
      protected 6-cyanouridine and 6-cyano-2'-deoxyuridine without the protection at
      the N(3)-imide and provides a facile and general access to versatile 6
      alkyluracil and 6-alkyluridine derivatives.

PMID- 23535023
TI  - Pyoderma gangrenosum associated with an aseptic splenic abscess in a patient with
      neurofibromatosis.
AB  - Pyoderma gangrenosum (PG) is a painful, ulcerating neutrophilic dermatosis
      commonly associated with a variety of underlying systemic conditions. We report a
      child with neurofibromatosis-1 (NF-1) and an aseptic splenic abscess who
      developed multifocal PG in areas of iatrogenic skin trauma. There is no clinical
      evidence or theoretical basis to suggest a causal relationship between NF-1 and
      PG. Systemic corticosteroid and cyclosporine therapy led to complete resolution
      of the lesions. 

PMID- 23535024
TI  - Cancer survivors in the United States: prevalence across the survivorship
      trajectory and implications for care.
AB  - BACKGROUND: Cancer survivors represent a growing population, heterogeneous in
      their need for medical care, psychosocial support, and practical assistance. To
      inform survivorship research and practice, this manuscript will describe the
      prevalent population of cancer survivors in terms of overall numbers and
      prevalence by cancer site and time since diagnosis. METHODS: Incidence and
      survival data from 1975-2007 were obtained from the Surveillance, Epidemiology,
      and End Results Program and population projections from the United States Census
      Bureau. Cancer prevalence for 2012 and beyond was estimated using the Prevalence
      Incidence Approach Model, assuming constant future incidence and survival trends
      but dynamic projections of the U.S. population. RESULTS: As of January 1, 2012,
      approximately 13.7 million cancer survivors were living in the United States with
      prevalence projected to approach 18 million by 2022. Sixty-four percent of this
      population have survived 5 years or more; 40% have survived 10 years or more; and
      15% have survived 20 years or more after diagnosis. Over the next decade, the
      number of people who have lived 5 years or more after their cancer diagnosis is
      projected to increase approximately 37% to 11.9 million. CONCLUSIONS: A
      coordinated agenda for research and practice is needed to address cancer
      survivors' long-term medical, psychosocial, and practical needs across the
      survivorship trajectory. IMPACT: Prevalence estimates for cancer survivors across
      the survivorship trajectory will inform the national research agenda as well as
      future projections about the health service needs of this population.

PMID- 23535025
TI  - Adipocytokines as features of the metabolic syndrome determined using
      confirmatory factor analysis.
AB  - PURPOSE: Confirmatory factor analysis (CFA) was used to test the hypothesis
      whether adipocytokines are associated with the risk factor cluster that
      characterizes the metabolic syndrome (MetS). METHODS: Data from 134 nondiabetic
      subjects were analyzed using CFA. Insulin sensitivity (SI) was quantified using
      intravenous glucose tolerance tests, visceral fat area by computed tomography and
      fasting high-density lipoprotein, triglycerides, monocyte chemoattractant protein
      1 (MCP-1), serum amyloid A (SAA), tumor necrosis factor (TNF)-alpha, adiponectin,
      resistin, leptin, interleukin (IL)-6, C-reactive protein (CRP), and plasminogen
      activator inhibitor (PAI)-1 were measured. RESULTS: The basic model representing
      the MetS included six indicators comprising obesity, SI, lipids, and
      hypertension, and demonstrated excellent goodness of fit. Using multivariate
      analysis, MCP-1, SAA, and TNF-alpha were not independently associated with any of
      the MetS variables. Adiponectin, resistin, leptin, CRP, and IL-6 were associated
      with at least one of the risk factors, but when added to the basic model
      decreased all goodness-of-fit parameters. PAI-1 was associated with all
      cardiometabolic factors and improved goodness-of-fit compared with the basic
      model. CONCLUSIONS: Addition of PAI-1 increased the CFA model goodness of fit
      compared with the basic model, suggesting that this protein may represent an
      added feature of the MetS.

PMID- 23535026
TI  - Sociodemographic, clinical, and psychological factors associated with attrition
      in a prospective study of cardiovascular prevention: the Heart Strategies
      Concentrating on Risk Evaluation study.
AB  - PURPOSE: To identify factors associated with attrition in a longitudinal study of
      cardiovascular prevention. METHODS: Demographic, clinical, and psychosocial
      variables potentially associated with attrition were investigated in 1841
      subjects enrolled in the southwestern Pennsylvania Heart Strategies Concentrating
      on Risk Evaluation study. Attrition was defined as study withdrawal, loss to
      follow-up, or missing 50% or more of study visits. RESULTS: Over 4 years of
      follow-up, 291 subjects (15.8%) met criteria for attrition. In multivariable
      regression models, factors that were independently associated with attrition were
      black race (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.55-3.16; P <
      .001), younger age (OR per 5-year increment, 0.88; 95% CI, 0.79-0.99; P < .05),
      male gender (OR, 1.79; 95% CI, 1.27-2.54; P < .05), no health insurance (OR,
      2.04; 95% CI, 1.20-3.47; P < .05), obesity (OR, 1.80; 95% CI, 1.07-3.02; P <
      .05), CES-D depression score 16 or higher (OR, 2.02; 95% CI, 1.29-3.19; P < .05),
      and higher ongoing life events questionnaire score (OR, 1.09; 95% CI, 1.04-1.13;
      P < .001). Having a spouse/partner participating in the study was associated with
      lower odds of attrition (OR, 0.60; 95% CI, 0.37-0.97; P < .05). A synergistic
      interaction was identified between black race and depression. CONCLUSIONS:
      Attrition over 4 years was influenced by sociodemographic, clinical, and
      psychological factors that can be readily identified at study entry. Recruitment
      and retention strategies targeting these factors may improve participant follow
      up in longitudinal cardiovascular prevention studies.

PMID- 23535027
TI  - Comments on the use of expiratory time constant for determinations of plateau
      pressure, respiratory system compliance, and total resistance.

PMID- 23535028
TI  - Identification of a histone acetyltransferase as a novel regulator of Drosophila
      intestinal stem cells.
AB  - One of the major challenges in stem cell research is to decipher the controlling
      mechanisms/genes of stem cell homeostasis. Through an RNAi mediated genetic
      screen of living animals, we identified an evolutionarily conserved histone
      acetyltransferase Atac2 as a novel regulator of Drosophila intestinal stem cells
      (ISCs). Expression of Atac2-RNAi or a dominant negative allele of Atac2 generated
      more ISCs, while excessive Atac2 or a histone deacetylase inhibitor promoted ISC
      differentiation without affecting ISC survival or lineage specification. These
      findings extend our knowledge of epigenetic mechanisms in stem cell regulation.

PMID- 23535029
TI  - Transcription factor TnrA inhibits the biosynthetic activity of glutamine
      synthetase in Bacillus subtilis.
AB  - The Bacillus subtilis glutamine synthetase (GS) plays a dual role in cell
      metabolism by functioning as catalyst and regulator. GS catalyses the ATP
      dependent synthesis of glutamine from glutamate and ammonium. Under nitrogen-rich
      conditions, GS becomes feedback-inhibited by high intracellular glutamine levels
      and then binds transcription factors GlnR and TnrA, which control the genes of
      nitrogen assimilation. While GS-bound TnrA is no longer able to interact with
      DNA, GlnR-DNA binding is shown to be stimulated by GS complex formation. In this
      paper we show a new physiological feature of the interaction between glutamine
      synthetase and TnrA. The transcription factor TnrA inhibits the biosynthetic
      activity of glutamine synthetase in vivo and in vitro, while the GlnR protein
      does not affect the activity of the enzyme.

PMID- 23535030
TI  - Leptin in nucleus of the solitary tract alters the cardiovascular responses to
      aortic baroreceptor activation.
AB  - Recent data suggests that neurons expressing the long form of the leptin receptor
      form at least two distinct groups within the caudal nucleus of the solitary tract
      (NTS): a group within the lateral NTS (Slt) and one within the medial (Sm) and
      gelantinosa (Sg) NTS. Discrete injections of leptin into Sm and Sg, a region that
      receives chemoreceptor input, elicit increases in arterial pressure (AP) and
      renal sympathetic nerve activity (RSNA). However, the effect of microinjections
      of leptin into Slt, a region that receives baroreceptor input is unknown.
      Experiments were done in the urethane-chloralose anesthetized, paralyzed and
      artificially ventilated Wistar or Zucker obese rat to determine leptin's effect
      in Slt on heart rate (HR), AP and RSNA during electrical stimulation of the
      aortic depressor nerve (ADN). Depressor sites within Slt were first identified by
      the microinjection of l-glutamate (Glu; 0.25M; 10nl) followed by leptin
      microinjections. In the Wistar rat leptin microinjection (50ng; 20nl) into
      depressor sites within the lateral Slt elicited increases in HR and RSNA, but no
      changes in AP. Additionally, leptin injections into Slt prior to Glu injections
      at the same site or to stimulation of the ADN were found to attenuate the
      decreases in HR, AP and RSNA to both the Glu injection and ADN stimulation. In
      Zucker obese rats, leptin injections into NTS depressor sites did not elicit
      cardiovascular responses, nor altered the cardiovascular responses elicited by
      stimulation of ADN. Those data suggest that leptin acts at the level of NTS to
      alter the activity of neurons that mediate the cardiovascular responses to
      activation of the aortic baroreceptor reflex.

PMID- 23535031
TI  - Additive effects between prematurity and postnatal risk factors of suicidal
      behavior.
AB  - BACKGROUND: Pre- and perinatal insults increase suicide risk. The main objective
      of the present study is to investigate if prematurity interacts in an additive
      fashion with postnatal risk factors of suicidal behavior. METHOD: Sample and
      procedure: 857 adult suicide attempters consecutively hospitalized for a suicide
      attempt were included. Studied characteristics of suicide attempts included use
      of a violent mean, age at first suicide attempt, and number of suicide attempts.
      Risk factors of suicidal behavior included indexes of pre- and perinatal
      adversity, childhood maltreatment as measured with the Childhood Trauma
      Questionnaire, personality traits as measured with the Tridimensional Personality
      Questionnaire, and family history of suicidal behavior. STATISTICAL ANALYSES:
      Comparisons between the different patterns of suicide attempts characteristics
      were made using logistic regression with crude and adjusted odds ratios and 95%
      confidence intervals. RESULTS: The risk of violent suicide attempts increased
      significantly in patients born prematurely (OR [95%] = 2.38[1.12-5.08]). There
      were additive effects for very preterm birth and 1) emotional abuse (OR [95% CI]
      = 4.52 [1.75-11.60]), 2) novelty seeking (OR [95% CI] = 8.92[3.09-25.7]), and 3)
      harm avoidance (OR [95% CI] = 5.81 [2.43-13.90]) on the age at first suicide
      attempt, after adjustment for potential confounders. CONCLUSIONS: Very preterm
      birth appears to be the first step in a cascade of stressors across lifetime,
      which affects the risk and the severity of suicidal behavior. Furthermore, very
      preterm birth, childhood maltreatment and personality traits have additive
      effects that influence the age at onset of suicide attempt. Our findings may have
      potential consequences for preventive policies.

PMID- 23535032
TI  - Factors associated with recovery from anorexia nervosa.
AB  - Previous studies of prognostic factors of anorexia nervosa (AN) course and
      recovery have followed clinical populations after treatment discharge. This
      retrospective study examined the association between prognostic factors--eating
      disorder features, personality traits, and psychiatric comorbidity--and
      likelihood of recovery in a large sample of women with AN participating in a
      multi-site genetic study. The study included 680 women with AN. Recovery was
      defined as the offset of AN symptoms if the participant experienced at least one
      year without any eating disorder symptoms of low weight, dieting, binge eating,
      and inappropriate compensatory behaviors. Participants completed a structured
      interview about eating disorders features, psychiatric comorbidity, and self
      report measures of personality. Survival analysis was applied to model time to
      recovery from AN. Cox regression models were used to fit associations between
      predictors and the probability of recovery. In the final model, likelihood of
      recovery was significantly predicted by the following prognostic factors:
      vomiting, impulsivity, and trait anxiety. Self-induced vomiting and greater trait
      anxiety were negative prognostic factors and predicted lower likelihood of
      recovery. Greater impulsivity was a positive prognostic factor and predicted
      greater likelihood of recovery. There was a significant interaction between
      impulsivity and time; the association between impulsivity and likelihood of
      recovery decreased as duration of AN increased. The anxiolytic function of some
      AN behaviors may impede recovery for individuals with greater trait anxiety.

PMID- 23535034
TI  - Quantifying the contribution of video in combined video-magnetoencephalographic
      ictal recordings of epilepsy patients.
AB  - INTRODUCTION: Magnetoencephalography (MEG) measures magnetic fields generated by
      neuronal currents. MEG is complementary to EEG. Considerable body of evidence
      indicates that ictal MEG recordings can provide useful information for pre
      surgical evaluation of epilepsy patients alongside the more established long-term
      ictal video-EEG. Ictal MEG is recorded in some epilepsy surgery centers. However,
      a wider adoption of ictal MEG is hampered by lack of tools for synchronized video
      MEG recording similar to those of video-EEG. METHODS: We have augmented MEG with
      a synchronized behavioral video-recording system. To estimate its additional
      value in ictal recordings, we retrospectively analyzed recordings of 10 epilepsy
      patients with and without the video. RESULTS: In six patients out of ten, adding
      the video substantially changed the resulting interpretations. In all six cases
      the effect was considerable: the number of detected seizures changed by more than
      50%. CONCLUSIONS: Synchronized video and audio recording capabilities are
      important for effective ictal MEG recordings of epilepsy patients.

PMID- 23535033
TI  - Genome-wide association study of the rate of cognitive decline in Alzheimer's
      disease.
AB  - BACKGROUND: Substantial interindividual variability exists in the disease
      trajectories of Alzheimer's disease (AD) patients. Some decline rapidly whereas
      others decline slowly, and there are no known explanations for this variability.
      We describe the first genome-wide association study to examine rate of cognitive
      decline in a sample of AD patients with longitudinal measures of cognition.
      METHODS: The discovery sample was 303 AD cases recruited in the Alzheimer's
      Disease Neuroimaging Initiative and the replication sample was 323 AD cases from
      the Religious Orders Study and Rush Memory and Aging Project. In the discovery
      sample, Alzheimer's Disease Assessment Scale-cognitive subscale responses were
      tested for association with genome-wide single-nucleotide polymorphism (SNP) data
      using linear regression. We tested the 65 most significant SNPs from the
      discovery sample for association in the replication sample. RESULTS: We
      identified SNPs in the spondin 1 gene (SPON1), the minor alleles of which were
      significantly associated with a slower rate of decline (rs11023139, P = 7.0 * 10(
      11)) in the discovery sample. A SPON1 SNP 5.5 kb upstream was associated with
      decline in the replication sample (rs11606345, P = .002). CONCLUSION: SPON1 has
      not been previously associated with AD risk, but is plausibly related because the
      gene product binds to the amyloid precursor protein and inhibits its cleavage by
      beta-secretase. These data suggest that SPON1 may be associated with the
      differential rate of cognitive decline in AD.

PMID- 23535035
TI  - Routine polysomnography in an epilepsy monitoring unit.
AB  - Up to 13% of patients with epilepsy have moderate or severe sleep-disordered
      breathing, in particular obstructive sleep apnea (OSA), a disorder associated
      with reduced quality of life, worsened seizure control, and increased
      cardiovascular morbidity and mortality. Combining video-EEG monitoring with
      polysomnography (VPSG) provides the opportunity to diagnose clinically
      significant OSA as well as relate the occurrence of seizures and the epilepsy
      diagnosis to the presence and severity of sleep-disordered breathing. We have
      established routine VPSG in our inpatient video-EEG monitoring unit and present
      our findings in 87 patients. Clinically significant sleep-disordered breathing
      was diagnosed in 19 of 87 (22%) patients. Patients with psychogenic non-epileptic
      seizures (PNES) had poorer sleep quality compared to patients with epilepsy and
      those with neither diagnosis, whereas the prevalence of clinically significant
      sleep-disordered breathing in patients with PNES (29%) did not differ
      significantly compared to patients with epilepsy (21%) and those with neither
      diagnosis (22%). The differences in sleep quality are not explained by
      differences in body mass index (BMI) or anti-epileptic drug (AED) effects.

PMID- 23535036
TI  - Epileptic encephalopathy after HHV6 post-transplant acute limbic encephalitis in
      children: confirmation of a new epilepsy syndrome.
AB  - Generalised epilepsy and cognitive deterioration were recently described in three
      children following human herpesvirus 6 (HHV6)-associated post-transplant acute
      limbic encephalitis (PALE). Magnetic resonance imaging (MRI) showed bilateral
      signal change and/or atrophy in the medial temporal structures and there was no
      evidence of an ongoing viral or immune-mediated process. We report another child
      who developed this condition after cord blood transplantation for congenital
      neutropenia at the age of three. He presented with epileptic spasms four months
      after HHV6-associated PALE. Cognitive regression, prominent
      electroencephalographic abnormalities and different types of generalised seizures
      ensued during the following months and proved refractory to antiepileptic and
      immunomodulating treatment, which included steroids, immunoglobulin and
      rituximab. MRI was normal at onset of epilepsy but subsequently showed the
      development of right hippocampal sclerosis. Results from serial blood and
      cerebrospinal fluid (CSF) analyses were inconclusive, including lack of patient's
      CSF and serum reactivity with cultures of dissociated rat hippocampal neurons.
      This report confirms the existence of a new epilepsy syndrome featuring
      generalised seizures and epileptic encephalopathy after HHV6-associated PALE in
      children. Presentation with epileptic spasms, lack of CSF and serum reactivity
      with cultured rat hippocampal neurons, and rituximab inefficacy are novel
      features that contribute to delineate the syndrome and argue against an immune
      mediated basis of this condition. 

PMID- 23535037
TI  - MRI of iron oxide nanoparticle-labeled ADSCs in a model of hindlimb ischemia.
AB  - Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of
      ischemic diseases. However, studies on the fate, migration, differentiation, and
      body distribution of the labeled ADSCs are rarely reported. In this study,
      magnetic iron oxide nanoparticles were designed, synthesized, and coated with
      meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs).
      The properties, size distribution, and characterization of DMSA-NPs were
      evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained
      and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation
      capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled
      GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic
      resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently
      labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability,
      proliferation, cell cycle, and multi-differentiation capacity. The MRI showed
      hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian
      blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the
      labeled GFP-ADSCs were in and around the ischemic sites and some differentiated
      into capillaries. This observation is identical to that seen for transplants of
      unlabeled cells. Labeled cells were also identified mainly in the liver and
      spleen, with significantly smaller amounts in the lungs, intestines, heart, and
      kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use
      as nanoprobes for MRI of stem cells, which will enhance our understanding of cell
      based therapeutic strategies for ischemic diseases.

PMID- 23535038
TI  - Interrelationships between LGBT-based victimization, suicide, and substance use
      problems in a diverse sample of sexual and gender minorities.
AB  - Research has documented significant relationships between sexual and gender
      minority stress and higher rates of suicidality (i.e. suicidal ideation and
      attempts) and substance use problems. We examined the potential mediating role of
      substance use problems on the relationship between sexual and gender minority
      stress (i.e. victimization based on lesbian, gay, bisexual, or transgender
      identity [LGBT]) and suicidality. A nonprobability sample of LGBT patients from a
      community health center (N = 1457) ranged in age from 19-70 years. Participants
      reported history of lifetime suicidal ideation and attempts, substance use
      problems, as well as experiences of LGBT-based verbal and physical attacks.
      Substance use problems were a significant partial mediator between LGBT-based
      victimization and suicidal ideation and between LGBT-based victimization and
      suicide attempts for sexual and gender minorities. Nuanced gender differences
      revealed that substance use problems did not significantly mediate the
      relationship between victimization and suicide attempts for sexual minority men.
      Substance use problems may be one insidious pathway that partially mediates the
      risk effects of sexual and gender minority stress on suicidality. Substances
      might be a temporary and deleterious coping resource in response to LGBT-based
      victimization, which have serious effects on suicidal ideation and behaviors.

PMID- 23535039
TI  - Preliminary results of the initial United States experience with the Supera woven
      nitinol stent in the popliteal artery.
AB  - BACKGROUND: Popliteal artery stenting is not routinely performed due to concerns
      related to the high mobility of the knee joint and the potential for external
      stent compression, fractures, and occlusion. Open bypass is traditionally
      considered the gold standard for popliteal artery atherosclerotic lesions. The
      Supera stent (IDEV Technologies Inc, Webster, Tex) was developed to provide
      superior radial strength, fracture resistance, and flexibility compared with
      laser-cut nitinol stents. This study represents the initial United States
      experience in the management of popliteal artery atherosclerotic disease with the
      Supera interwoven wire stent. METHODS: Patients undergoing stent implantation in
      the 20-month period after the 2008 Food and Drug Administration clearance were
      included. Medical records, radiographic imaging, and procedural data were
      examined. Procedural angiograms were classified according to Trans-Atlantic Inter
      Society Consensus criteria. Patency and limb loss rates were calculated using
      Kaplan-Meier analysis. RESULTS: A total of 39 stents were placed in 34 patients
      due to isolated popliteal artery occlusive disease. Clinical follow-up was a mean
      of 12.7 months (range, 0.2-33.7 months), and radiologic follow-up was a mean of
      8.4 months (range, 0-26.8 months). Most patients had critical limb ischemia
      (CLI), with tissue loss (38.2%) or rest pain (35.3%) as the indication for
      intervention. In 20 patients (58.8%), the most distal end of the stent(s) landed
      in the below-the-knee popliteal segment, 12 (35.3%) landed in the above-the-knee
      segment, and two (5.9%) landed precisely at the knee. Other than angioplasty and
      stenting, 47% of patients did not receive any adjuvant concomitant therapy in the
      treated leg. Two patients underwent concomitant atherectomy of the popliteal
      segment. Primary, primary assisted, and secondary patency rates by duplex
      ultrasound imaging were 79.2%, 88.1% and 93%, respectively, by Kaplan-Meier
      estimates, with a mean stented length of 12 cm. Six instances of stent occlusion
      were noted, and six patients were identified with hemodynamically significant in
      stent stenosis. Three patients sustained limb loss (8.8%), two related to
      uncontrolled infections, and one due to perioperative ischemic complications
      (both with patent stents at the time of limb loss). The overall mortality was
      8.8% during the study period. Knee roentgenography was performed in all but one
      patient, and no stent fractures were identified. CONCLUSIONS: Stenting of the
      popliteal artery using the Supera stent system appears to be safe and effective.
      The interwoven stent design may better serve areas under extreme mechanical
      stress. Our results with this highly diseased patient population justify a
      prospective trial in this subject.

PMID- 23535040
TI  - Adult coarctation of aorta with postcoarct dissecting aortic aneurysm
      successfully repaired under circulatory arrest.

PMID- 23535041
TI  - Traumatic arteriovenous fistula involving the subclavian artery and jugular vein.

PMID- 23535042
TI  - Thirty years with a chronic juxtarenal aortic occlusion.

PMID- 23535043
TI  - A systematic review of preoperative duplex ultrasonography and arteriovenous
      fistula formation.
AB  - BACKGROUND: Arteriovenous fistula (AVF) formation for dialysis access is a common
      procedure. Fistula maturation is unpredictable. Preoperative duplex mapping may
      increase procedural success. We undertook a systematic review to assess the
      effect of preoperative duplex mapping on subsequent AVF patency. METHODS: The
      published literature was searched on PubMed and the Cochrane Library using the
      following keywords: 'arteriovenous fistula,' 'venous mapping,' 'ultrasound,'
      'hemodialysis,' 'vascular access,' and 'perioperative vessel mapping.' Conference
      proceedings were hand searched for otherwise unpublished trials. Only randomized
      controlled trials in which preoperative duplex mapping was compared with clinical
      evaluation were eligible. RESULTS: Three trials (402 patients) were identified.
      More patients who underwent ultrasound successfully started using their fistula
      for dialysis access, although the difference did not reach statistical
      significance (174/214 vs 130/188; pooled odds ratio, 1.96; P = .11). CONCLUSIONS:
      Preoperative duplex mapping may improve fistula maturation rates. However, the
      results do not reach statistical significance and there are no cost-effectiveness
      data. Further work is required.

PMID- 23535044
TI  - Medicine versus religion in the surgical intensive care unit: who is in charge?
AB  - The chief of surgery at a large academic medical center is approached by a
      vascular surgical faculty member. After a repair of an aortic dissection, an
      elderly man has remained comatose and has worsened over several weeks, developing
      multiple system organ failure. Statistically, his chance of leaving the hospital
      alive is <1%. The family is deeply religious, and the minister and various
      elders, deacons, and members of their church have been vigilant in constant
      prayerful attendance. The attending's tactful suggestions that the time is coming
      when nature should be allowed to take its course was not well received. The
      family and their support group are convinced that their fervor will summon a
      miracle. A large group complained to patient affairs and was taken to the medical
      center director's office. Today, the director told the attending that the
      hospital would absorb the overall cost until the patient dies and that the
      unfavorable press from stopping care is unacceptable. The chief of surgery
      should:

PMID- 23535046
TI  - Regarding "Quality of vascular surgery web sites on the internet".

PMID- 23535047
TI  - Regarding "Preoperative prediction of mortality within 1 year after elective
      thoracic endovascular aortic aneurysm repair".

PMID- 23535048
TI  - Reply: To PMID 22801107.

PMID- 23535049
TI  - Transplantation of mouse CGR8 embryonic stem cells producing GDNF and TH protects
      against 6-hydroxydopamine neurotoxicity in the rat.
AB  - Embryonic stem cells (ESCs)-based therapies have been increasingly recognized as
      a potential tool to replace or support cells and their function damaged by the
      neurodegenerative process that underlies Parkinson's disease (PD). In this study,
      we implanted engineered mouse embryonic stem (ES) CGR8 cells, which stably co
      express glial cell line-derived neurotrophic factor (GDNF) and tyrosine
      hydroxylase (TH), into striatum (Str) or both Str and substantia nigra (SN) of
      parkinsonian rats lesioned by 6-hydroxydopamine (6-OHDA). We found that cell
      transplantation into Str or both Str and SN rescued behavioral abnormalities and
      striatal DA depletion associated with 6-OHDA lesion. Our findings suggested that
      the profound functional impairment in nigrostriatal circuitry could be at least
      partially restored by ESCs-based expression of TH and GDNF, which may be
      developed into a useful tool for PD therapy.

PMID- 23535050
TI  - Neuronal cytotoxicity and genotoxicity induced by zinc oxide nanoparticles.
AB  - Zinc oxide nanoparticles (ZnO NPs) are one of the most abundantly used
      nanomaterials in consumer products and biomedical applications. As a result,
      human exposure to these NPs is highly frequent and they have become an issue of
      concern to public health. Although toxicity of ZnO NPs has been extensively
      studied and they have been shown to affect many different cell types and animal
      systems, there is a significant lack of toxicological data for ZnO NPs on the
      nervous system, especially for human neuronal cells and tissues. In this study,
      the cytotoxic and genotoxic effects of ZnO NPs on human SHSY5Y neuronal cells
      were investigated under different exposure conditions. Results obtained by flow
      cytometry showed that ZnO NPs do not enter the neuronal cells, but their presence
      in the medium induced cytotoxicity, including viability decrease, apoptosis and
      cell cycle alterations, and genotoxicity, including micronuclei production, H2AX
      phosphorylation and DNA damage, both primary and oxidative, on human neuronal
      cells in a dose- and time-dependent manner. Free Zn(2+) ions released from the
      ZnO NPs were not responsible for the viability decrease, but their role on other
      types of cell damage cannot be ruled out. The results obtained in this work
      contribute to increase the knowledge on the genotoxic and cytotoxic potential of
      ZnO NPs in general, and specifically on human neuronal cells, but further
      investigations are required to understand the action mechanism underlying the
      cytotoxic and genotoxic effects observed.

PMID- 23535051
TI  - What Is LARC? And why does it matter for adolescents and young adults?

PMID- 23535052
TI  - Myths and misconceptions about long-acting reversible contraception (LARC).
AB  - PURPOSE: To discuss common myths and misconceptions about long-acting reversible
      contraception (LARC) among patients and health care providers. METHODS: We
      address some of these common myths in an effort to provide clinicians with
      accurate information to discuss options with patients, parents, and referring
      providers. The list of myths was created through an informal survey of an online
      listserv of 200 family planning experts and from the experiences of the authors.
      RESULTS: When presented with information about LARC, adolescents are more likely
      to request LARC and are satisfied with LARC. Clinicians have an important role in
      counseling about and providing LARC to their adolescent patients as well as
      supporting them in managing associated side effects. CONCLUSIONS: This review
      article can be used as a resource for contraceptive counseling visits and for the
      continuing education of health professionals providing adolescent reproductive
      health care.

PMID- 23535053
TI  - Intrauterine devices and pelvic inflammatory disease among adolescents.
AB  - Adolescents may be ideal candidates for intrauterine device (IUD) use, given high
      rates of unintended pregnancy and less successful use of short-acting
      contraceptive methods. Concerns about elevated risks of pelvic inflammatory
      disease in adolescents, with the consequences of infertility, ectopic pregnancy,
      and pelvic pain, prevent many clinicians from inserting IUDs in adolescents. The
      body of evidence examining risks of pelvic infection related to IUD use
      specifically in adolescents is limited, but is reassuring that the absolute risk
      of pelvic infection is small and that the benefits of IUD use likely outweigh the
      risks.

PMID- 23535054
TI  - Dual use of long-acting reversible contraceptives and condoms among adolescents.
AB  - Unintended pregnancy and sexually transmitted infections (STI) continue to be
      significant public health problems, and adolescents are disproportionately
      affected by both. With national attention and funding directed toward adolescent
      pregnancy prevention, promotion of long-acting reversible contraceptive (LARC)
      use among adolescents is both timely and relevant. However, LARCs provide no
      protection against STIs, requiring dual-method use of both LARC and barrier
      methods, most commonly the male latex condom, to address these issues
      simultaneously. Rates of both LARC and dual-method contraception are low in the
      United States, but have increased in recent years. Dual-method contraception is
      highest among younger women and adolescents with multiple or new sex partners.
      Consistent condom use remains a major barrier to dual-method use, as it
      necessitates admission of STI risk by both partners, and use is dependent upon
      two decision-makers rather than a single contraceptive user. Promoting the
      initiation and maintenance of LARC and condom use across multiple partnered
      sexual encounters requires understanding of individual, dyadic, and social
      influences. Successful maintenance of contraceptive and STI prevention behaviors
      requires individualized, longitudinal reinforcement, and social supports, but can
      ultimately reduce the burden of unintended pregnancy and STI among adolescents.

PMID- 23535055
TI  - Awareness of long-acting reversible contraception among teens and young adults.
AB  - Adolescents and young women were historically excluded from receiving long-acting
      reversible contraceptives (LARC) such as intrauterine devices (IUDs) after
      widespread concerns about infection and infertility 40 years ago reduced IUD use
      for all women. Over the last several years, concerted efforts by professional
      health organizations have promoted LARC as an excellent solution to the epidemic
      of unintended pregnancy in adolescents and young adults, yet uptake has increased
      slowly. In this article we review evidence regarding awareness of LARC among
      young women, and perceptions and knowledge of LARC in this population. We review
      evidence on clinical providers' knowledge and beliefs about LARC, and their
      beliefs about the appropriateness or risks of LARCs for adolescents and young
      women. We discuss an active role for providers in increasing awareness of LARC
      among young women, rather than relying on patient request for methods of which
      they have little knowledge. Finally, we suggest avenues of future research into
      the most effective and efficient ways to increase awareness of LARC among
      adolescents.

PMID- 23535056
TI  - Practical tips for intrauterine devices use in adolescents.
AB  - The American Congress of Obstetricians and Gynecologists (ACOG) has endorsed
      intrauterine devices (IUDs) as first-line contraceptive choices for both
      nulliparous and parous adolescents. The committee opinion did address some of the
      practical elements of IUD use in adolescents, but because these practical
      concerns may be barriers to use for both teens and clinicians, this review is
      devoted to "practical tips," based on the available literature as well as the
      author's clinical experience. Counseling, informed consent, techniques of pain
      management, and preventive guidance about possible side effects are addressed in
      an effort to promote successful use of this long-acting reversible contraception
      (LARC) option.

PMID- 23535057
TI  - The effect of long-acting reversible contraception on rapid repeat pregnancy in
      adolescents: a review.
AB  - Repeat pregnancy within 2 years of a previous birth or abortion occurs in
      approximately 35% of recently pregnant female adolescents. The majority of these
      pregnancies are classified as unintended with about half ending in births and the
      remainder in abortions. Rapid repeat pregnancy (RRP) is associated with increased
      maternal and neonatal morbidity and continues a cycle of economic deprivation for
      young women and their families. Immediately following a pregnancy, most young
      women report an intention to avoid pregnancy in the near future, but many change
      their minds or become ambivalent within months. Lack of contraceptive use is more
      common among those teens that resume sexual intercourse earlier, live with a male
      partner, had a preterm delivery, or had an intended teen pregnancy. Adolescents
      who do not initiate a long-acting reversible contraceptive (LARC) method
      (intrauterine device or contraceptive implant) have up to a 35 times increased
      risk of RRP compared with their peers using LARC. Risk of RRP is decreased when
      LARC methods are initiated earlier after an abortion or within the postpartum
      period. This review will focus on the prevalence of RRP, the risk factors for
      RRP, and the effectiveness of strategies to reduce unintended RRP including
      counseling and early initiation of long-acting contraceptive methods.

PMID- 23535058
TI  - Use of levonorgestrel intrauterine system for medical indications in adolescents.
AB  - The levonorgestrel intrauterine system (LNG-IUS) is an underused contraceptive
      method in adolescent populations. In addition to being a highly effective,
      reversible, long-acting contraception, the LNG-IUS has many noncontraceptive
      health benefits including reduced menstrual bleeding, decreased dysmenorrhea and
      pelvic pain related to endometriosis, and menstruation suppression in teens with
      physical or developmental disabilities. The LNG-IUS can also provide endometrial
      protection in teens with chronic anovulation, and may be used to treat
      endometrial hyperplasia and cancer. This review examines the evidence supporting
      the use of the LNG-IUS in adolescents for these noncontraceptive benefits.

PMID- 23535059
TI  - Cost as a barrier to long-acting reversible contraceptive (LARC) use in
      adolescents.
AB  - Cost is a major barrier to adolescents' ability to obtain long-acting reversible
      contraception (LARC). By reviewing the available literature on this issue, we
      provide a framework to understand how insurance coverage, out-of-pocket expenses,
      parental involvement, and recent pregnancy can impact access. We provide examples
      of cost-free access to LARC for adolescents, such as the Contraceptive CHOICE
      Project. Universal coverage for contraception, without cost-sharing, could
      increase use of LARC among adolescents resulting in fewer unintended pregnancies,
      improved health outcomes, and considerable cost savings to the healthcare system.

PMID- 23535060
TI  - Counseling adolescents about contraception: towards the development of an
      evidence-based protocol for contraceptive counselors.
AB  - Research on contraceptive counseling of adolescents in clinics and service
      delivery settings is considered. The provider context as well as the
      developmental context of adolescence is characterized and their implications for
      contraceptive counseling are explicated. After reviewing research on the
      effectiveness of contraceptive counseling, it was concluded there is little
      empirical evidence to support the efficacy of current practices considered as a
      totality. Twelve principles for effective contraceptive counseling were then
      derived as a basis for building an evidence-based contraceptive counseling
      protocol for adolescents.

PMID- 23535061
TI  - Examining non-response bias in substance use research--are late respondents
      proxies for non-respondents?
AB  - BACKGROUND: Non-response is a major concern among substance use epidemiologists.
      When differences exist between respondents and non-respondents, survey estimates
      may be biased. Therefore, researchers have developed time-consuming strategies to
      convert non-respondents to respondents. The present study examines whether late
      respondents (converted former non-participants) differ from early respondents,
      non-consenters or silent refusers (consent givers but non-participants) in a
      cohort study, and whether non-response bias can be reduced by converting former
      non-respondents. METHODS: 6099 French- and 5720 German-speaking Swiss 20-year-old
      males (more than 94% of the source population) completed a short questionnaire on
      substance use outcomes and socio-demographics, independent of any further
      participation in a cohort study. Early respondents were those participating in
      the cohort study after standard recruitment procedures. Late respondents were non
      respondents that were converted through individual encouraging telephone contact.
      Early respondents, non-consenters and silent refusers were compared to late
      respondents using logistic regressions. Relative non-response biases for early
      respondents only, for respondents only (early and late) and for consenters
      (respondents and silent refusers) were also computed. RESULTS: Late respondents
      showed generally higher patterns of substance use than did early respondents, but
      lower patterns than did non-consenters and silent refusers. Converting initial
      non-respondents to respondents reduced the non-response bias, which might be
      further reduced if silent refusers were converted to respondents. CONCLUSION:
      Efforts to convert refusers are effective in reducing non-response bias. However,
      converted late respondents cannot be seen as proxies of non-respondents, and are
      at best only indicative of existing response bias due to persistent non
      respondents.

PMID- 23535062
TI  - Impact of isolated germline JAK2V617I mutation on human hematopoiesis.
AB  - The association between somatic JAK2 mutation and myeloproliferative neoplasms
      (MPNs) is now well established. However, because JAK2 mutations are associated
      with heterogeneous clinical phenotypes and often occur as secondary genetic
      events, some aspects of JAK2 mutation biology remain to be understood. We
      recently described a germline JAK2V617I mutation in a family with hereditary
      thrombocytosis and herein characterize the hematopoietic and signaling impact of
      JAK2V617I. Through targeted sequencing of MPN-associated mutations, exome
      sequencing, and clonality analysis, we demonstrate that JAK2V617I is likely to be
      the sole driver mutation in JAK2V617I-positive individuals with thrombocytosis.
      Phenotypic hematopoietic stem cells (HSCs) were increased in the blood and bone
      marrow of JAK2V617I-positive individuals and were sustained at higher levels than
      controls after xenotransplantation. In signaling and transcriptional assays,
      JAK2V617I demonstrated more activity than wild-type JAK2 but substantially less
      than JAK2V617F. After cytokine stimulation, JAK2V617I resulted in markedly
      increased downstream signaling compared with wild-type JAK2 and comparable with
      JAK2V617F. These findings demonstrate that JAK2V617I induces sufficient cytokine
      hyperresponsiveness in the absence of other molecular events to induce a
      homogeneous MPN-like phenotype. We also provide evidence that the JAK2V617I
      mutation may expand the HSC pool, providing insights into both JAK2 mutation
      biology and MPN disease pathogenesis.

PMID- 23535063
TI  - MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in
      the first complete remission: results from the AML05 multicenter trial.
AB  - We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the
      first complete remission (CR1) by applying risk-directed therapy based on minimal
      residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk
      directed therapy included recommending allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous
      HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status
      after the second consolidation rather than induction or first consolidation could
      discriminate high-risk relapse patients (P = .001). Allo-HSCT could reduce
      relapse and improve survival compared with chemotherapy for high-risk patients
      (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free
      survival [DFS]: 61.7% vs 19.6%, P = .001), whereas chemotherapy/auto-HSCT
      achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients.
      Multivariate analysis revealed that MRD status and treatment choice were
      independent prognostic factors for relapse, DFS, and OS. We concluded that MRD
      status after the second consolidation may be the best timing for treatment
      choice. MRD-directed risk stratification treatment may improve the outcome of
      t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR
      OCH-12002406.

PMID- 23535065
TI  - Do health and education agencies in the United States share responsibility for
      academic achievement and health? A review of 25 years of evidence about the
      relationship of adolescents' academic achievement and health behaviors.
AB  - PURPOSE: The United States Centers for Disease Control and Prevention monitors
      health-risk behaviors of adolescents in United States, which include (1)
      violence; (2) tobacco use; (3) alcohol and other drug use; (4) sexual behaviors
      contributing to unintended pregnancy and sexually transmitted diseases; (5)
      inadequate physical activity; and (6) unhealthy dietary behaviors. We reviewed
      original research published in peer-reviewed journals between 1985 and 2010 to
      synthesize evidence about the association of adolescent health-risk behaviors and
      academic achievement. METHODS: Using predetermined selection criteria, 122
      articles were included that used at least one variable for health-risk behaviors
      and also for academic achievement. RESULTS: For all six health-risk behaviors,
      96.6% of the studies reported statistically significant inverse relationships
      between health-risk behaviors and academic achievement. CONCLUSIONS: With this
      persuasive evidence about the interrelationship of health-risk behaviors and
      academic achievement, it is imperative that leaders in education and health act
      together to make wise investments in our nation's school-age youth that will
      benefit the entire population. A unified system that addresses both health
      behavior and academic achievement would have reciprocal and synergistic effects
      on the health and academic achievement not only of children and adolescents, but
      also of adults in the United States.

PMID- 23535064
TI  - Tat engagement of p38 MAP kinase and IRF7 pathways leads to activation of
      interferon-stimulated genes in antigen-presenting cells.
AB  - As a result of its interaction with transcription factors, HIV type 1 (HIV-1) Tat
      can modulate the expression of both HIV and cellular genes. In antigen-presenting
      cells Tat induces the expression of a subset of interferon (IFN)-stimulated genes
      (ISGs) in the absence of IFNs. We investigated the genome-wide Tat association
      with promoters in immature dendritic cells and in monocyte-derived macrophages.
      Among others, Tat associated with the MAP2K6, MAP2K3, and IRF7 promoters that are
      functionally part of IL-1 and p38 mitogen-activated protein kinase (MAPK)
      signaling pathways. The association correlated with their increased gene
      expression, increased activation of p38 MAPK and of phosphorylated signal
      transducer and activator of transcription 1 (STAT1), and consequent induction of
      ISGs. Probing these pathways with RNA interference, pharmacological p38 MAPK
      inhibition, and in cell lines lacking STAT1s or the type I IFN receptor chain
      confirmed the role of MAPKKs and IRF7 in Tat-mediated modulation of ISGs and
      excluded the involvement of IFNs in this modulation. Tat interaction with the 2
      MAPKK and IRF7 promoters in HIV-1-infected cells and the resulting persistent
      activation of ISGs, which include inflammatory cytokines and chemokines, can
      contribute to the increased immune activation that characterizes HIV infection.

PMID- 23535066
TI  - Merkel cell polyomavirus detection in a patient with familial epidermodysplasia
      verruciformis.
AB  - We report a case of Merkel cell polyomavirus detection in the skin of a patient
      with epidermodysplasia verruciformis (EDV) and a family history remarkable for an
      unusual inheritance pattern for EDV. 

PMID- 23535067
TI  - Synthesis of gamma-, delta-, and epsilon-lactams by asymmetric transfer
      hydrogenation of N-(tert-butylsulfinyl)iminoesters.
AB  - Highly enantiomerically enriched gamma- and delta-lactams have been prepared by a
      simple and very efficient procedure that involves the asymmetric transfer
      hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of
      the nitrogen atom and spontaneous cyclization to the desired lactams during the
      basic workup procedure. Five- and six-membered ring lactams bearing aromatic,
      heteroaromatic, and aliphatic substituents have been obtained in very high yields
      and ee's up to >99%. A slight modification of the procedure also allowed the
      preparation of epsilon-lactams in good yields and very high enantioselectivities.
      Both enantiomers of the final lactams could be prepared with equal efficiency by
      changing the absolute configuration of the sulfinyl chiral auxiliary.

PMID- 23535068
TI  - Role of reactive oxygen species and NADPH-oxidase in the development of rat
      cerebellum.
AB  - Experimental evidence suggests that reactive oxygen species (ROS) could
      participate in the regulation of some physiological conditions. In the nervous
      system, ROS have been suggested to act as signaling molecules involved in several
      developmental processes including cell differentiation, proliferation and
      programmed of cell death. Although ROS can be generated by several sources, it
      has been suggested that NADPH oxidase (NOX) could be critical in the production
      of ROS acting as a signal in some of these events. It has been reported that ROS
      production by NOX enzymes participate in neuronal maturation and differentiation
      during brain development. In the present study, we found that during rat
      cerebellar development there was a differential ROS generation at different ages
      and areas of the cerebellum. We also found a differential expression of NOX
      homologues during rat cerebellar development. When we treated developing rats
      with an antioxidant or with apocynin, an inhibitor of NOX, we found a marked
      decrease of the ROS levels in all the cerebellar layers at all the ages tested.
      Both treatments also induced a significant change in the cerebellar foliation as
      well as an alteration in motor behavior. These results suggest that both ROS and
      NOX have a critical role during cerebellar development.

PMID- 23535069
TI  - The effects of Fasciola hepatica tegumental antigens on mast cell function.
AB  - Fasciola hepatica infection is associated with T helper 2/T regulatory immune
      responses and increased mast cell numbers. The aim of this study was to examine
      the interaction between F. hepatica tegumental coat antigen and mast cells in
      vivo and in vitro. Firstly, BALB/C, C57BL/6 or STAT6(-/-) mice were infected with
      F. hepatica metacercarie or mice were treated with F. hepatica tegumental coat
      antigen and then mast cells numbers in the peritoneal cavity and/or the liver
      were quantified. Also, the proliferation, chemotaxis, degranulation and cytokine
      secretion of mast cells from bone marrow or from peritoneal exudate cells
      stimulated with F. hepatica tegumental coat antigen were measured. Finally, we
      tested whether F. hepatica tegumental coat antigen inhibits degranulation of mast
      cells in vivo in a passive cutaneous and systemic anaphylaxis mouse model. Mast
      cell numbers increased in the peritoneal cavity and liver of F. hepatica infected
      mice, and this was mimicked by injection of F. hepatica tegumental coat antigen
      in a STAT6(-/-) independent manner. The increase in mast cell number was not the
      result of F. hepatica tegumental coat antigen-induced proliferation; rather F.
      hepatica tegumental coat antigen indirectly induces mast cell migration by
      dendritic cell-derived chemokines. Fasciola hepatica tegumental coat antigen
      interactions with mast cells do not drive T helper 2 or T regulatory immune
      responses. These studies on mast cell and F. hepatica tegumental coat antigen
      interaction may help us to understand the function of mast cells in immunity
      against F. hepatica and the immunomodulatory effect of F. hepatica tegumental
      coat antigen on these cells.

PMID- 23535070
TI  - Structural model of a putrescine-cadaverine permease from Trypanosoma cruzi
      predicts residues vital for transport and ligand binding.
AB  - The TcPOT1.1 gene from Trypanosoma cruzi encodes a high affinity putrescine
      cadaverine transporter belonging to the APC (amino acid/polyamine/organocation)
      transporter superfamily. No experimental three-dimensional structure exists for
      any eukaryotic member of the APC family, and thus the structural determinants
      critical for function of these permeases are unknown. To elucidate the key
      residues involved in putrescine translocation and recognition by this APC family
      member, a homology model of TcPOT1.1 was constructed on the basis of the atomic
      co-ordinates of the Escherichia coli AdiC arginine/agmatine antiporter crystal
      structure. The TcPOT1.1 homology model consisted of 12 transmembrane helices with
      the first ten helices organized in two V-shaped antiparallel domains with
      discontinuities in the helical structures of transmembrane spans 1 and 6. The
      model suggests that Trp241 and a Glu247-Arg403 salt bridge participate in a
      gating system and that Asn245, Tyr148 and Tyr400 contribute to the putrescine
      binding pocket. To test the validity of the model, 26 site-directed mutants were
      created and tested for their ability to transport putrescine and to localize to
      the parasite cell surface. These results support the robustness of the TcPOT1.1
      homology model and reveal the importance of specific aromatic residues in the
      TcPOT1.1 putrescine-binding pocket.

PMID- 23535071
TI  - Molecular diagnosis of cystic echinococcosis in humans from central Poland.
AB  - The identity of the causative agent of cystic echinococcosis (CE) in humans from
      central Poland receiving treatment between 2000 and 2010 was determined. A total
      of 47 samples obtained after hepatectomy were examined and protoscoleces were
      identified in wet preparations in 27 cases. Using DNA extracted from the samples,
      two mitochondrial regions (nad1 and cox1 genes) were amplified and the nad1
      fragment was sequenced. This PCR analysis confirmed the presence of Echinococcus
      species in 30 cases and nad1 sequence alignments showed identity with the G7
      (pig) strain, Echinococcus canadensis. These data demonstrate that the pig strain
      of this parasite is the most frequent causative agent of human cystic
      echinococcosis in central Poland.

PMID- 23535072
TI  - Taming the wild-types: targeting PAK1 in melanomas that lack BRAF mutations.

PMID- 23535074
TI  - Re: Physical activity and risks of proximal and distal colon cancers: a
      systematic review and meta-analysis.

PMID- 23535073
TI  - P21-activated kinase 1 (PAK1) as a therapeutic target in BRAF wild-type melanoma.
AB  - BACKGROUND: Although remarkable clinical response rates in melanoma have been
      observed using vemurafenib or dabrafenib in patients with tumors carrying
      oncogenic mutations in BRAF, a substantial unmet medical need remains for the
      subset of patients with wild-type BRAF tumors. METHODS: To investigate the role
      of p21-activated kinases (PAKs) in melanoma, we determined PAK1 genomic copy
      number and protein expression for a panel of human melanoma tissues. PAK1 was
      inhibited in vitro and in vivo using RNA interference or PF-3758309 inhibitor
      treatment in a panel of melanoma cell lines with known BRAF and RAS (rat sarcoma)
      genotype to better understand its role in melanoma cell proliferation and
      migration. Tumorigenesis was assessed in vivo in female NCR nude mice and
      analyzed with cubic spline regression and area under the curve analyses. All
      statistical tests were two-sided. RESULTS: Strong cytoplasmic PAK1 protein
      expression was prevalent in melanomas (27%) and negatively associated with
      activating mutation of the BRAF oncogene (P < .001). Focal copy number gain of
      PAK1 at 11q13 was also observed in 9% of melanomas (n = 87; copy number >= 2.5)
      and was mutually exclusive with BRAF mutation (P < .005). Selective PAK1
      inhibition attenuated signaling through mitogen-activated protein kinase (MAPK)
      as well as cytoskeleton-regulating pathways to modulate the proliferation and
      migration of BRAF wild-type melanoma cells. Treatment of BRAF wild-type melanomas
      with PF-3758309 PAK inhibitor decreased tumor growth for SK-MEL23 and 537MEL
      xenografts (91% and 63% inhibition, respectively; P < .001) and MAPK pathway
      activation in vivo. CONCLUSIONS: Taken together, our results provide evidence for
      a functional role of PAK1 in BRAF wild-type melanoma and therapeutic use of PAK
      inhibitors in this indication.

PMID- 23535075
TI  - Descriptive factors of abusive head trauma in young children--United States, 2000
      2009.
AB  - OBJECTIVE: Abusive head trauma (AHT) is a leading cause of severe injury in
      maltreated children in the United States. There is little research from
      nationally representative datasets available to characterize young children who
      had AHT compared to non-abusive head trauma (NAHT). METHODS: Using the recent CDC
      AHT case definition, we performed a retrospective analysis of 2000, 2003, 2006
      and 2009 hospitalization data using the Kids' Inpatient Database (KID) from the
      Healthcare Cost and Utilization Project. Logistic regression was used to compare
      AHT to NAHT patients <2 years of age. Socio-demographic data and indicators of
      socioeconomic status (i.e., insurance status and household income), presence of
      chronic conditions, injury severity (i.e., length of hospital stay and vital
      status), hospital specialization (i.e., hospital type), hospital region, and
      season of admission were used as independent variables. RESULTS: A weighted
      sample of 7,603 AHT and 25,339 NAHT patients was identified. National rates for
      AHT were 39.8 per 100,000 population for children <1 year and 6.8 per 100,000
      population for children 1 year old. Compared to NAHT, children with AHT were more
      often <1 year of age (adjusted odds ratio [aOR]=2.66; 95% confidence interval
      [CI]: 2.35-3.01), male (aOR=1.10; 95% CI: 1.01-1.20), enrolled in Medicaid
      (aOR=2.78; 95% CI: 2.49-3.11), hospitalized longer (aOR=8.26; 95% CI: 7.24-9.43),
      died during hospitalization (aOR=5.12; 95% CI: 4.01-6.53), and seen at children's
      hospitals (aOR=1.97; 95% CI: 1.63-2.38) and hospitals outside the Northeast
      [aOR=2.65 (95% CI: 2.10-3.33) for the Midwest, 1.90 (95% CI: 1.52-2.38) for the
      South and 1.93 (95% CI: 1.45-2.57) for the West, respectively]. CONCLUSIONS: The
      results confirm that injuries from AHT are more severe and more often lethal than
      other head injuries. Socioeconomically disadvantaged families with children <1
      year are an important focus for primary prevention. The associations of AHT,
      compared to NAHT with hospital type and hospital region warrant further
      investigation. Referral or reporting patterns, or true differences in the
      incidence may contribute to the identified associations.

PMID- 23535076
TI  - Correlation between insight dimensions and cognitive functions in patients with
      deficit and nondeficit schizophrenia.
AB  - Previous studies have shown correlations between poor insight and neurocognitive
      impairment in schizophrenia. Deficit schizophrenia has been associated with worse
      cognitive functioning and poorer insight. This study aimed at investigating the
      relationship between insight dimensions (measured by Schedule for the Assessment
      of Insight-Expanded Version and its factors) and specific neurocognitive
      functions (assessed through a battery of neuropsychological tests) considering
      separately patients with deficit (n=29) and nondeficit schizophrenia (n=44),
      categorized according to the Schedule for the Deficit Syndrome. We found that
      working memory correlated positively and significantly with awareness of mental
      illness in both groups. In nondeficit group, awareness of mental illness
      correlated additionally with verbal fluency and attention. If confirmed by
      further studies, these results may have important consequences, such as the need
      of tailoring differently cognitive rehabilitation for each group.

PMID- 23535077
TI  - Is magnetic resonance imaging sufficient to diagnose rudimentary uterine horn? A
      case report and review of the literature.
AB  - Imaging is often part of the evaluation of gynecologic disorders, with
      transvaginal ultrasound being the most frequently used imaging modality. Although
      laparoscopy, hysterosalpingography, and hysteroscopy can add diagnostic accuracy,
      they are invasive and costly. Magnetic resonance imaging (MRI) has been
      increasingly used because it is both noninvasive and highly accurate. Although
      MRI is more expensive than ultrasound, it is less so than surgery. Given the
      demonstrated accuracy of MRI in assessing mullerian anomalies, additional imaging
      is not often sought once an MRI diagnosis is made. However, when imaging findings
      are not pathognomonic via MRI or otherwise, inaccurate diagnoses and their
      consequences may occur. We describe the case of a 21-year-old woman with
      unilateral dysmenorrhea whose MRI features suggested a unicornuate uterus with a
      hematometrous noncommunicating horn although laparoscopy ultimately revealed a
      necrotic myoma without an accompanying mullerian anomaly. 

PMID- 23535078
TI  - Mental state and quality of life after 10 session whole-body cryotherapy.
AB  - The aim of this study was to evaluate the impact of a whole-body cryotherapy
      (WBCT) on various parameters of the mental state of patients depending on their
      age, gender, and diagnosed illness. The study included 55 subjects - 43 women and
      12 men aged from 20 to 70 years. Based on the diagnosed illness, the patients
      were divided into two diagnostic groups. The first group consisted of patients
      with spinal pain syndromes (n = 34). The second group comprised patients with
      peripheral joint disease (n = 21). All patients underwent 10 WBCT sessions. The
      subjects completed a survey at two time points: before the first WBCT treatment
      (T1) and after completing the tenth treatment (T2). The World Health Organization
      Quality of Life-Bref (WHOQOL-Bref) questionnaire and the Psychological General
      Well-Being Index (PGWBI) questionnaire were used in the study. After a series of
      WBCT treatments, the WHOQOL-Bref and PGWBI scores significantly improved (p =
      .005161, p = .000862, respectively). WBCT proved to be more effective in
      enhancing the mood and well-being of the patients than in improving their quality
      of life. WBCT has a significant influence on improving the well-being and mood of
      patients (in terms of both psychological and somatic aspects) and consequently
      leads to an improvement in their quality of life. The worse the mental state of
      the patients is prior to the cryotherapy, the stronger its effect. The observed
      effectiveness of cryotherapy was the strongest in women, patients with spinal
      pains and in patients with severe depressive symptoms.

PMID- 23535079
TI  - Physical activity intensity and cardiovascular risk by ankle-brachial index.
AB  - A low ankle-brachial index (ABI) is associated with increased risk for
      cardiovascular events and mortality. Physical inactivity in individuals with a
      low ABI may further increase their risk for cardiovascular events. The purpose of
      this paper is to examine the relationship between the intensity of free-living
      physical activity and cardiovascular disease (CVD) risk by ABI status. During
      2003-2004, the National Health and Nutrition Examination Survey included an
      accelerometer module and collected ABI data. Individuals were classified as
      having a normal (1-1.4) or low (< 1) ABI. The Framingham risk score (FRS) was
      used to determine CVD risk. Multiple linear regression was used to determine the
      association of total accelerometer counts and time spent at various physical
      activity intensity levels with FRS by ABI groups. Individuals with a low ABI
      spent less time engaging in moderate-to-vigorous intensity physical activity
      (MVPA) (9.1 min/day vs 13.2 min/day; p = 0.06) when compared to those with a
      normal ABI. There were no differences in light intensity physical activity (LPA)
      or sedentary behavior between ABI groups. Total accelerometer counts were
      inversely related to FRS. MVPA, but not LPA, was inversely related to FRS in both
      normal and low ABI groups (p < 0.001 and p = 0.001, respectively). In conclusion,
      these findings suggest that even modestly higher levels of physical activity may
      be beneficial for secondary risk prevention in this high-risk group.

PMID- 23535080
TI  - Study of the transfer of 137Cs from fodder to cow milk in the region around
      Narora Atomic Power Station NPP Site, India.
AB  - Site-specific transfer coefficient from feed to cow's milk, for (137)Cs in the
      villages around Narora, a nuclear power station site in India, determined over a
      period of 17 y, is presented in this paper. In the transport model for the
      prediction of the concentration of (137)Cs in milk, the transfer coefficient from
      feed to milk, Fm, is an important parameter. The transfer coefficient value is
      determined from (137)Cs concentration in milk and grass samples of the Narora
      region, and the result ranged from 4.28E-03 to 3.30E-02 d l(-1) with a geometric
      mean value of 1.15E-03 d l(-1). The highest and the lowest values were only below
      one order of magnitude different from the mean, regardless of the type of diet,
      milk yield and age of the cow. The result is compared with that for (40)K,
      determined concurrently at the same region and ranged from 6.92E-03 to 8.01E-03 d
      l(-1) with a geometric mean value of 7.45E-03 d l(-1). This parameter is quite
      useful in decision-making for implementing countermeasures during a large-area
      contamination with (137)Cs in tropical areas like Narora. The ingestion dose from
      fallout (137)Cs through milk intake for adult and child is also estimated. 

PMID- 23535081
TI  - The evaluation of urine activity and external dose rate from patients receiving
      radioiodine therapy for thyroid cancer.
AB  - The aim of this study was to determine the external dose rate of iodine retention
      as a function of time in the bodies of thyroid cancer patients during their
      isolation period in the hospital. Urine samples were collected at 6th, 12th,
      18th, 24th h and 2nd, 3rd, 4th, 5th d from 83 patients after oral administration
      of (131)I and counted. The external dose rates were also simultaneously
      determined at the same time points. Then, it was expressed as retained
      radioiodine body activity versus dose rate. Effective half life calculated from
      urine sample measurements was found as 18.4+/-1.8 h within the first 24 h and
      64+/-2.7 h between 48 and 120 h. According to this results, the external dose
      rate (<20 uSv h(-1)), which patients could be discharged, was achieved after 48 h
      for 3700 and 5550 MBq, and after 72 h for 7400 MBq of (131)I treatments. 

PMID- 23535082
TI  - Allergic fungal rhinosinusitis.

PMID- 23535083
TI  - The American College of Allergy, Asthma & Immunology: a 70-year legacy of
      accomplishments (1942-2012), part 2: events and achievements (1992-2012).

PMID- 23535084
TI  - Mechanisms of disease for the clinician: systemic lupus erythematosus.
AB  - OBJECTIVE: To review the complex interactions and processes in systemic lupus
      erythematosus (SLE). DATA SOURCES: Brief review of the important literature in
      peer-reviewed journals. STUDY SELECTION: Studies on the clinical and immunologic
      features, pathogenesis, epidemiology, laboratory evaluation, and treatment of SLE
      are included in this review. RESULTS: SLE may include a variety of disease
      entities, such as isolated cutaneous lupus, undifferentiated connective tissue
      disease, mixed connective tissue disease, and drug-induced lupus. There are many
      ongoing clinical trials in SLE patients of therapeutics with different mechanisms
      of cellular action, such as classic immunosuppression, cell depletion, antigen
      specific immunomodulation, and targeting of antigen-nonspecific, immune
      activating molecules. New immune cell-targeted therapies are now available that
      are specifically designed to block cellular pathways involved in disease
      pathogenesis. CONCLUSION: The practicing physician should understand the
      immunology, pathogenesis, laboratory evaluation, and updated treatment options
      when diagnosing SLE in their clinic or daily practice.

PMID- 23535085
TI  - Targeting the small airways asthma phenotype: if we can reach it, should we treat
      it?
AB  - OBJECTIVE: To review the available methods of evaluating the small airways
      disease in asthma and the therapeutic strategies to achieve better control using
      emerging extrafine particle inhaler technologies. DATA SOURCES: The PubMed,
      MEDLINE (Ebsco), Scirus, Scopus, and Google Scholar databases were all scanned
      with Cross-search using the following keywords: asthma, small airways,
      hydrofluoroalkane 134a, extrafine particle, inhaled corticosteroid, long-acting
      beta-agonist, spirometry, impulse oscillometry, nitrogen washout, exhaled nitric
      oxide, airway hyperresponsiveness, and adrenal suppression. STUDY SELECTION: Key
      clinical studies considered to being relevant to the topic under review were
      evaluated. RESULTS: There is an unmet need in current asthma guidelines for those
      individuals who exhibit the small airways asthma phenotype with a preserved
      forced expiratory volume in 1 second but abnormal forced midexpiratory flow and
      peripheral airway resistance, which tends to be associated with poorer control.
      Extrafine hydrofluoroalkane solution formulations of inhaled corticosteroid
      either alone or in combination with long-acting beta-agonist may improve small
      airways outcomes and associated control. CONCLUSION: From a pragmatic
      perspective, it makes sense to try to deliver asthma treatment to more of the
      lung to improve clinical outcomes, especially in patients who exhibit the small
      airways asthma phenotype.

PMID- 23535086
TI  - Age-related differences in asthma outcomes in the United States, 1988-2006.
AB  - BACKGROUND: Relatively little is known about the effect of age on asthma outcomes
      in adults, particularly at a national level. OBJECTIVE: To investigate age
      related differences in asthma outcomes in a nationally representative,
      longitudinal study. METHODS: We analyzed data from the Third National Health and
      Nutrition Examination Survey (1988-1994) with linked mortality files through
      2006. Adults with physician-diagnosed asthma were identified and were divided
      into 2 age groups: younger adults (17-54 years of age) and older adults (55 years
      or older). The outcome measures were both cross-sectional (health care use,
      comorbidity, and lung function) and longitudinal (all-cause mortality). RESULTS:
      There were an estimated 9,566,000 adults with current asthma. Of these, 73% were
      younger adults and 27% older adults. Compared with younger adults, older adults
      had more hospitalizations in the past year, more comorbidities, and poorer lung
      function (eg, lower forced expiratory volume in 1 second) (P < .05 for all).
      During a median follow-up of 15 years, significant baseline predictors of higher
      all-cause mortality included older age (>=55 vs <55 years old: adjusted hazard
      ratio [HR], 6.77; 95% confidence interval [CI], 3.15-14.54), poor health status
      (fair and poor vs excellent health status: adjusted HR, 10.07; 95% CI, 3.75
      27.01), and vitamin D deficiency (vitamin D level <30 vs >=50 nmol/L: adjusted
      HR, 2.19; 95% CI, 1.05-4.58), whereas Mexican American ethnicity (adjusted HR,
      0.31; 95% CI, 0.14-0.65) was associated with lower mortality. Controlling for
      age, asthma was not associated with increased all-cause mortality (adjusted HR,
      1.28; 95% CI, 0.99-1.65). CONCLUSION: Older adults with asthma have a substantial
      burden of morbidity and increased mortality. The ethnic differences in asthma
      mortality and the vitamin D-mortality link merit further investigation.

PMID- 23535088
TI  - Obstructive sleep apnea is associated with reduced quality of life in adult
      patients with asthma.
AB  - BACKGROUND: Recent data suggest that obstructive sleep apnea (OSA) is an
      important contributor to severe uncontrolled asthma. OBJECTIVE: To investigate
      the clinical characteristics, asthma control, and asthma-related quality of life
      in adult patients with asthma at a high risk for OSA. METHODS: A total of 217
      patients with asthma who visited our tertiary-care clinic were randomly
      recruited. They completed the Berlin questionnaire, which screens for OSA risk, a
      quality-of-life questionnaire for adult Korean patients with asthma (QLQAKA), and
      underwent an asthma control test (ACT). Fraction of exhaled nitric oxide (FeNO),
      lung function, blood lipid profiles, and body composition were evaluated.
      RESULTS: The mean age was 58.4 +/- 15.4, and 91 (41.9%) were male. Eighty-nine
      subjects (41.0%) were classified as high risk for OSA from the Berlin
      questionnaire. Patients with a high OSA risk were significantly older, had a
      higher prevalence of hypertension, higher BMI, non-atopic predisposition, and
      longer asthma treatment duration in the baseline clinical characteristics. The
      high OSA risk group had a lower ACT score than the low OSA risk group, but it was
      not statistically significant (20.9 +/- 3.6 vs 21.5 +/- 3.3, P = .091). The
      QLQAKA score was significantly lower in the high OSA risk group compared with the
      low OSA risk group (64.4 +/- 10.9 vs 68.1 +/- 11.1, P = .026), especially in the
      activity-domain (P = .005). The FeNO was not significantly different between the
      2 groups. CONCLUSION: Quality of life is significantly decreased in adult
      patients with asthma with a high risk of OSA. Special consideration is needed for
      the care and treatment of patients with asthma who have a high risk of OSA.

PMID- 23535087
TI  - Characteristics of allergic sensitization among asthmatic adults older than 55
      years: results from the National Health and Nutrition Examination Survey, 2005
      2006.
AB  - BACKGROUND: Approximately 60% to 80% of children and young adults with asthma are
      sensitized to at least one allergen. In contrast, previous studies from specific
      subpopulations of older patients with asthma suggest that allergic sensitization
      is significantly lower in this age group. The prevalence and patterns of IgE
      mediated sensitization have not been compared among a broad population of younger
      and older patients with asthma. OBJECTIVE: To determine the prevalence and
      patterns of IgE-mediated sensitization among a broad population of younger and
      older patients with asthma. METHODS: Data were obtained from the National Health
      and Nutrition Examination Survey (NHANES) 2005-2006 to compare IgE-mediated
      sensitization rates between younger (20-40 years) and older (>=55 years) patients
      with current asthma. Atopy was defined as a detectable serum IgE to at least 1
      allergen in a panel of 19 allergens. The associations among sensitization,
      current asthma, and asthma control measures (health care use and symptoms) were
      examined by logistic regression. RESULTS: In a group of 2,573 patients, either 20
      to 40 years of age or 55 years or older, 108 (6.7%) and 43 (4.5%) patients with
      current asthma were identified, respectively. Allergic sensitization rates among
      the adults with asthma differed only moderately and not statistically
      significantly between the age groups; 75.4% of the younger and 65.2% of the older
      asthmatic patients were sensitized to at least 1 allergen. The association
      between sensitization and markers of asthma control did not appear to differ
      among the age groups. CONCLUSION: Allergic sensitization in older patients with
      asthma may be more common than previously reported.

PMID- 23535089
TI  - Clinical value of radiocontrast media skin tests as a prescreening and diagnostic
      tool in hypersensitivity reactions.
AB  - BACKGROUND: Some radiocontrast media (RCM) hypersensitivity reactions may have
      underlying IgE- or T-cell-mediated mechanisms. RCM skin testing may be useful for
      predicting future reactions. OBJECTIVE: To investigate the clinical value of RCM
      skin testing before computed tomography and after RCM hypersensitivity reactions.
      METHODS: Patients who underwent RCM skin testing were a prospective sample of
      convenience at a single medical center and were tested just before their pending
      nonionic RCM-enhanced computed tomogram. In addition, skin test data of patients
      who were referred to the allergy clinic because of their previous RCM
      hypersensitivity reactions were reviewed retrospectively. RESULTS: A total of
      1048 patients enrolled in the study prospectively. Of these, 672 (64.1%) had
      never been exposed to RCM. Of the 376 previously exposed to RCM, 61 (16.2%) had a
      history of at least one mild RCM-associated reaction, 56 (91.8%) had immediate
      reactions, and 5 had no-immediate reactions. There was only 1 positive immediate
      hypersensitivity RCM skin test result (0.09%). There were 51 mild immediate
      reactions (4.9%), 1 moderate immediate reaction (0.09%), 8 mild nonimmediate
      reactions (0.76%), and 1 moderate nonimmediate reaction (0.09%). There was only 1
      positive delayed hypersensitivity skin test result (0.09%), retrospectively
      determined, in 1 (11.1%) of the nonimmediate RCM-associated reactions.
      Sensitivity of RCM skin testing was significantly higher with severe immediate
      reactions (57.1%) than mild reactions (12.9%) and moderate reactions (25.0%) in
      the retrospective review of diagnostic skin test data (P = .03). CONCLUSION: RCM
      skin testing for screening is of no clinical utility in predicting
      hypersensitivity reactions. RCM skin testing may have modest utility in
      retrospectively evaluating severe adverse reactions.

PMID- 23535090
TI  - Prevention of nonsteroidal inflammatory drug-induced urticaria and/or angioedema.
AB  - BACKGROUND: Urticaria and/or angioedema (U/AE) are the most frequent and less
      severe forms of nonallergic hypersensitivity reactions to nonsteroidal anti
      inflammatory drugs (NSAIDs). Management of NSAID-induced U/AE includes (1) the
      avoidance of the culprit drug and of cyclooxygenase (COX) 1 inhibitors, (2) the
      use of weak COX-2 inhibitors, and/or (3) desensitization to aspirin. Because
      these possibilities may have drawbacks, we tested the possibility of preventing
      NSAID-induced U/AE by the administration of antihistamines and/or a combination
      of antihistamines and leukotriene antagonists. OBJECTIVE: To test the preventive
      effect of antihistamines and/or leukotriene antagonists on the development of
      U/AE in patients with a history of NSAID hypersensitivity confirmed by a positive
      challenge result. METHODS: A single, placebo-controlled, oral challenge using the
      culprit NSAID was applied to 65 patients with a history of NSAID-induced U/AE. In
      the case of recurrence of the symptoms, another oral challenge was performed
      under premedication with antihistamines alone or combined antihistamines and
      leukotriene antagonists. RESULTS: A total of 59 of 65 patients (90%) tolerated a
      normal dose of NSAID, confirming previous data on the poor reproducibility of
      nonallergic hypersensitivity reactions to NSAIDs on challenge. Of the 6 patients
      who experienced recurrence of the U/AE on NSAID challenge, antihistamines and
      combined antihistamines and leukotriene antagonists prevented the
      hypersensitivity reactions in 2 and 3 of them, respectively. Only 1 patient still
      developed a moderate NSAID-induced urticaria despite the double premedication.
      CONCLUSION: Treatment with NSAIDs at normal doses is possible and well tolerated
      in patients who have experienced NSAID-induced U/AE, which could be prevented by
      the concomitant use of antihistamines and leukotriene antagonists.

PMID- 23535091
TI  - Induction of accelerated reactions to amoxicillin by T-cell effector mechanisms.
AB  - BACKGROUND: Although allergic drug reactions have been considered to be immediate
      (IgE mediated) or delayed (T-cell effector mechanisms), accelerated reactions
      have also been defined; however, they have not been sufficiently studied.
      OBJECTIVE: To study the mechanisms involved in accelerated reactions to
      amoxicillin. METHODS: We monitored the response in 3 patients who had an
      accelerated reaction to amoxicillin. A T-cell effector response was searched
      after a Drug Provocation Test. Symptoms were recorded after initiation of the
      reaction, and sequential samples were taken at different intervals after
      challenge. Skin biopsy specimens were also taken, and a lymphocyte transformation
      test (LTT) was performed. RESULTS: After the drug provocation test, all 3
      patients had a positive response within 2 to 6 hours of drug administration, with
      full expression at 6 hours, requiring corticoids and antihistamine treatment.
      They had generalized erythema with facial angioedema but no cardiovascular or
      respiratory symptoms. Monitoring of the response revealed the presence in the
      skin of CD4 and CD8 lymphocytes with increased expression of homing and cell
      activation markers. Immunohistochemistry revealed a perivascular mononuclear cell
      infiltrate with activated CD4 and CD8 cells expressing perforin and granzyme B.
      No tryptase release was detected in either the affected tissue or the peripheral
      blood. The LTT result was positive in all 3 patients. CONCLUSION: We found that
      accelerated reactions to beta-lactams are mediated by effector T cells. The
      increase in different T-cell markers and a positive LTT result to amoxicillin, in
      parallel with the occurrence of symptoms after challenge, support this mechanism.

PMID- 23535092
TI  - AAAAI and ACAAI surveillance study of subcutaneous immunotherapy, Year 3: what
      practices modify the risk of systemic reactions?
AB  - OBJECTIVE: To define the incidence of and clinical practices associated with
      subcutaneous immunotherapy (SCIT)-related systemic reactions (SRs). METHODS: From
      2008-2011, American Academy of Allergy, Asthma & Immunology and American College
      of Allergy, Asthma & Immunology members completed an annual survey of SCIT
      related SRs of varying severity (with grade 1 indicating mild; grade 2, moderate;
      and grade 3, severe anaphylaxis). From 2010-2011 (year 3) data were collected
      regarding SCIT-related procedures, including screening of patients with asthma,
      dose adjustment during peak pollen seasons, build-up regimens (conventional,
      cluster, or rush), and premedication. RESULTS: No fatal reactions were directly
      or indirectly reported from 2008-2011. The SR rates were similar for all 3 years
      (0.1% of injection visits; 83% of practices), as were severity grades. On
      average, for all 3 years, there were 7.1 grade 1, 2.6 grade 2, and 0.4 grade 3
      SRs per 10,000 injection visits. Screening for worsening asthma symptoms was
      highly prevalent (86% always screened). Practices that always reduced doses
      during peak pollen season were significantly less likely to report grade 2 or 3
      SRs (44% vs 65%; P = .04). Cluster and rush build-up were associated with
      significantly more SRs (P < .001). Practices that premedicated were significantly
      more likely to report grade 2 and 3 SRs (P < .01). CONCLUSION: Fatal reactions to
      SCIT appear to be declining, possibly related to almost universal screening of
      asthmatic patients. Adjusting doses during the pollen season may be associated
      with decreased risk for severe SRs. Cluster and rush immunotherapy were
      associated with increased risk for SRs. Premedication by practices reporting SRs
      likely reflects past experience with SRs.

PMID- 23535093
TI  - Role of parental atopy in cow's milk allergy: a population-based study.
AB  - BACKGROUND: A family history of atopy has been considered an independent risk
      factor for atopic diseases in children. OBJECTIVE: To relate the risk of an
      infant developing IgE-mediated cow's milk allergy (IgE-CMA) to the atopic status
      of parents. METHODS: Assessment of the parental atopic status of children with
      IgE-CMA (n = 66) previously identified in a large-scale prospective study was
      compared with the parental atopic status of a control group of healthy infants (n
      = 156). The atopic status was identified both by self-reporting and skin prick
      tests (SPTs). RESULTS: Analysis for the risk for infants to develop IgE-CMA
      depended on the assessment method used. No significant differences were noted in
      self-reported parental atopic status between the IgE-CMA patients and the control
      group. However, among the subgroup of infants with persistent IgE-CMA (n = 25),
      maternal but not paternal self-reporting for atopy was more likely compared with
      parents of the control group (P = .04). In contrast, when analyzed by SPT, in
      both this persistent subgroup and the total allergic cohort, no significant
      differences were noted whether analyzed by single parent or both parents and
      whether the parent tested singly or multiply positive on the SPT. CONCLUSION: In
      families with children with persistent IgE-CMA, self-reporting of atopy by
      parents may be biased. Furthermore, the demonstration of IgE-mediated responses
      to allergens in parents is insufficient by itself, in a general population
      cohort, to predict which infants are at greatest risk of developing IgE-CMA.

PMID- 23535094
TI  - Factors that predict the clinical reactivity and tolerance in children with cow's
      milk allergy.
AB  - BACKGROUND: Specific IgE (sIgE) may be used for the diagnosis of cow's milk
      allergy (CMA) and as a guide to perform food challenge tests in patients with
      CMA. The effect of genetic variants on the prognosis of food allergy is largely
      unknown. OBJECTIVE: To examine the performance of sIgE analysis and the utility
      of the genetic variants of CD14, STAT6, IL13, IL10, SPINK5, and TSLP in
      predicting the clinical course in children with CMA. METHODS: Serum sIgE levels
      of 94 children who underwent open food challenges and 54 children with
      anaphylaxis due to cow's milk (CM) were retrospectively analyzed between January
      2002 and May 2009. The genetic polymorphisms were determined in 72 children.
      RESULTS: A total of 148 children were followed up for a median of 3.5 years, and
      42 of the 94 challenge results were positive. The probability curves with 95%
      decision points were 2.8 kU/L for younger than 1 year, 11.1 for younger than 2
      years, 11.7 for younger than 4 years, and 13.7 for younger than 6 years. Sixty
      six children outgrew CMA during follow-up. Children with initial an CM sIgE level
      less than 6 kU/L outgrew CMA earlier than children with an initial CM sIgE level
      of 6 kU/L or higher (P < .001). The age of tolerance development for CM was
      significantly higher in children with the GG genotype at rs324015 of the STAT6
      gene compared with those with the AA+AG genotype (2 years [range, 1.5-3.9 years]
      vs 1.2 years [range, 1.0-2.2 years]) (P = .02). CONCLUSION: The decision points
      of sIgE obtained in different age groups may help to determine the likelihood of
      clinical reactivity more precisely. The results suggest that sIgE levels and
      STAT6 gene variants may be important determinants to predict longer persistence
      of CMA.

PMID- 23535095
TI  - Efficacy and safety of oral desensitization in children with cow's milk allergy
      according to their serum specific IgE level.
AB  - BACKGROUND: Oral desensitization in children allergic to cow's milk proteins is
      not risk free. The analysis of factors that may influence the outcome is of
      utmost importance. OBJECTIVE: To analyze the efficacy and safety of the oral
      desensitization according to specific IgE (sIgE) level and adverse events during
      the maintenance phase. METHODS: Thirty-six patients allergic to cow's milk (mean
      age, 7 years) were included in an oral desensitization protocol. Patients were
      grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE <3.5 kU/L), 2
      (3.5-17 kU/L), and 3 (>17-50 kU/L). Nineteen children were included as a control
      group. Serum sIgE levels to cow's milk and its proteins were determined at
      inclusion and 6 and 12 months after finishing the desensitization protocol.
      RESULTS: Thirty-three of 36 patients were successfully desensitized (200 mL):
      100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a
      median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of
      the patients in group 2, and 30% of the patients in group 3 achieved tolerance in
      less than 3 months (P = .04). In the control group only 1 child tolerated milk in
      oral food challenge after 1 year. During the induction phase, there were 53
      adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe
      adverse events compared with group 1. During the maintenance phase, 20 of 33
      patients (60%) had an adverse event. CONCLUSION: Oral desensitization is
      efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse
      events are frequent, especially in patients with higher sIgE levels.

PMID- 23535096
TI  - Efficacy and safety of recombinant C1 inhibitor for the treatment of hereditary
      angioedema attacks: a North American open-label study.
AB  - BACKGROUND: The efficacy of recombinant human C1 inhibitor (rhC1INH) for the
      treatment of patients with acute hereditary angioedema (HAE) attacks has been
      demonstrated in 2 randomized, double-blind, placebo-controlled studies.
      OBJECTIVE: To assess the safety and efficacy of rhC1INH for repeated treatment of
      acute attacks of HAE. METHODS: In this open-label extension study, patients with
      eligible HAE attacks were treated with an intravenous 50-U/kg dose of rhC1INH
      with an option for an additional dose of 50 U/kg based on clinical response. Time
      to beginning of relief was assessed by patients using a 100-mm visual analogue
      scale (VAS). Safety evaluation was based on the clinical laboratory results and
      adverse events. RESULTS: Sixty-two patients were treated for 168 attacks (range,
      1-8 attacks per patient). A total of 90% of the attacks were treated with a
      single 50-U/kg dose of rhC1INH. Median times to beginning of symptom relief for
      the first 5 attacks were 37 to 67 minutes. More than 90% of attacks responded
      within 4 hours after treatment with rhC1INH. There was no requirement for
      increased dosing with successive treatments. Thirty-nine patients (63%) reported
      at least 1 treatment-emergent adverse event, with most events rated mild to
      moderate. Seven severe treatment-emergent adverse events were reported, and all
      were considered to be unrelated to treatment with rhC1INH. CONCLUSION: The
      results of this open-label extension support continued efficacy of rhC1INH after
      repeated treatments for subsequent HAE attacks. There was no increase in adverse
      event reporting after repeated exposure to rhC1INH.

PMID- 23535097
TI  - Extracorporeal membrane oxygenation is indicated for status asthmaticus
      refractory to maximal conventional therapy.

PMID- 23535098
TI  - Successful intravaginal graded challenge after a systemic reaction with skin
      prick testing to seminal fluid.

PMID- 23535099
TI  - Optimal management of DRESS syndrome in course of infectious endocarditis.

PMID- 23535100
TI  - Anaphylactic reaction to dietary oats.

PMID- 23535101
TI  - Novel case of anaphylaxis to sturgeon fish.

PMID- 23535102
TI  - Successful rapid desensitization to hydrochlorothiazide.

PMID- 23535103
TI  - Successful desensitization protocol for pyridostigmine hypersensitivity in a
      patient with myasthenia gravis.

PMID- 23535104
TI  - Allergen of the month-European olive.

PMID- 23535105
TI  - Weight loss, weight maintenance, and adaptive thermogenesis.
AB  - BACKGROUND: Diet-induced weight loss is accompanied by adaptive thermogenesis,
      ie, a disproportional or greater than expected reduction of resting metabolic
      rate (RMR). OBJECTIVE: The aim of this study was to investigate whether adaptive
      thermogenesis is sustained during weight maintenance after weight loss. DESIGN:
      Subjects were 22 men and 69 women [mean +/- SD age: 40 +/- 9 y; body mass index
      (BMI; in kg/m(2)): 31.9 +/- 3.0]. They followed a very-low-energy diet for 8 wk,
      followed by a 44-wk period of weight maintenance. Body composition was assessed
      with a 3-compartment model based on body weight, total body water (deuterium
      dilution), and body volume. RMR was measured (RMRm) with a ventilated hood. In
      addition, RMR was predicted (RMRp) on the basis of the measured body composition:
      RMRp (MJ/d) = 0.024 * fat mass (kg) + 0.102 * fat-free mass (kg) + 0.85.
      Measurements took place before the diet and 8, 20, and 52 wk after the start of
      the diet. RESULTS: The ratio of RMRm to RMRp decreased from 1.004 +/- 0.077
      before the diet to 0.963 +/- 0.073 after the diet (P < 0.001), and the decrease
      was sustained after 20 wk (0.983 +/- 0.063; P < 0.01) and 52 wk (0.984 +/- 0.068;
      P < 0.01). RMRm/RMRp was correlated with the weight loss after 8 wk (P < 0.01),
      20 wk (P < 0.05), and 52 wk (P < 0.05). CONCLUSION: Weight loss results in
      adaptive thermogenesis, and there is no indication for a change in adaptive
      thermogenesis up to 1 y, when weight loss is maintained. This trial was
      registered at clinicaltrials.gov as NCT01015508.

PMID- 23535106
TI  - Low vitamin D concentration exacerbates adult brain dysfunction.

PMID- 23535107
TI  - Gastric cancer in Zambian adults: a prospective case-control study that assessed
      dietary intake and antioxidant status by using urinary isoprostane excretion.
AB  - BACKGROUND: Gastric cancer is increasingly recognized in Zambia. Although
      nutritional factors contribute to gastric cancer risk, their effect in Zambia is
      unknown. OBJECTIVE: The objective was to investigate the association between
      intake of dietary antioxidants, urinary 8-iso prostaglandin F2alpha (8-iso
      PGF2alpha) as a marker of oxidative stress, and gastric cancer. DESIGN: This was
      a case-control study at the University Teaching Hospital in Zambia. Gastric
      cancer cases were compared with age- and sex-matched controls. Urine 8-iso
      PGF2alpha was measured primarily by ELISA, and by gas chromatography-mass
      spectrometry in a subset, expressed as a ratio to creatinine. Blood was collected
      for Helicobacter pylori, HIV serology, gastrin-17, and pepsinogen 1 and 2
      concentrations. Clinical and dietary data were collected by using questionnaires.
      Food items were broadly classified into 7 major categories (fruit, vegetables,
      fish, meat, insects, cereals, and starches). RESULTS: Fifty cases with gastric
      cancer (mean age: 61 y; n = 31 males) and 90 controls (mean age: 54 y; n = 41
      males) were enrolled. Median urinary 8-iso PGF2alpha excretion was higher in
      cases (0.014; IQR: 0.008-0.021) than in controls (0.011; IQR: 0.006-0.018; P =
      0.039). On univariate analysis, habitual fruit intake was lower in cases than in
      controls during the dry season (P = 0.02). On multivariate analysis, smoking (OR:
      7.22; IQR: 1.38-37.9) and gastric atrophy (OR: 2.43; IQR: 1.12-5.13) were
      independently associated with cancer, and higher fruit intake was protective (OR:
      0.44; IQR: 0.20-0.95). Isoprostane excretion was inversely correlated with total
      fruit intake (rho = -0.23; n = 140; P = 0.006). CONCLUSION: Urinary 8-iso
      PGF2alpha excretion was associated with the risk of gastric cancer, as were
      smoking and gastric atrophy, but increased fruit intake conferred protection.
      This trial was registered at www.pactr.org as ISRCTN52971746.

PMID- 23535108
TI  - Kinetics of the utilization of dietary arginine for nitric oxide and urea
      synthesis: insight into the arginine-nitric oxide metabolic system in humans.
AB  - BACKGROUND: The systemic availability of oral/dietary arginine and its
      utilization for nitric oxide (NO) synthesis remains unknown and may be related to
      a competitive hydrolysis of arginine into urea in the splanchnic area and
      systemic circulation. OBJECTIVES: We investigated the kinetics and dose
      dependency of dietary arginine utilization for NO compared with urea synthesis
      and studied the characteristics of the arginine-NO metabolic system in healthy
      humans. DESIGN: We traced the metabolic fate and analyzed the utilization
      dynamics of dietary arginine after its ingestion at 2 nutritional amounts in
      healthy humans (n = 9) in a crossover design by using [(15)N-(15)N-(guanido)]
      arginine, isotope ratio mass spectrometry techniques, and data analysis with a
      compartmental modeling approach. RESULTS: Whatever the amount of dietary
      arginine, 60 +/- 3% (+/-SEM) was converted to urea, with kinetics indicative of a
      first-pass splanchnic phenomenon. Despite this dramatic extraction, intact
      dietary arginine made a major contribution to the postprandial increase in plasma
      arginine. However, the model identified that the plasma compartment was a very
      minor (~2%) precursor for the conversion of dietary arginine into NO, which, in
      any case, was small (<0.1% of the dose). The whole-body and plasma kinetics of
      arginine metabolism were consistent with the suggested competitive metabolism by
      the arginase and NO synthase pathways. CONCLUSIONS: The conversion of
      oral/dietary arginine into NO is not limited by the systemic availability of
      arginine but by a tight metabolic compartmentation at the systemic level. We
      propose an organization of the arginine metabolic system that explains the daily
      maintenance of NO homeostasis in healthy humans.

PMID- 23535109
TI  - Diets of drinkers on drinking and nondrinking days: NHANES 2003-2008.
AB  - BACKGROUND: Alcohol may affect dietary intake. However, little is known about
      diets on drinking days in the US population. OBJECTIVE: We determined whether the
      diets of drinkers differ on drinking compared with nondrinking days. DESIGN: Data
      were from the 2003-2008 NHANES Mobile Examination Center interview. We identified
      1864 current drinkers (1126 men and 738 women) who completed two 24-h dietary
      recalls, one of which was on a drinking day and the other of which was on a
      nondrinking day. Sex-specific repeated-measures analyses that were adjusted for
      dietary recall order and recall day of the week were used to compare within
      individual differences in energy, nutrient, and food-group intakes. Analyses were
      weighted to produce representative estimates. RESULTS: On their drinking
      (compared with nondrinking) days, men consumed an excess 168 nonalcohol kcal (P <
      0.01), which was reflected in higher intakes of nutrients including total protein
      (P < 0.001), total fat (P < 0.01), saturated fat (P < 0.01), monounsaturated fat
      (P < 0.01), potassium (P < 0.001), and sodium (P < 0.05). Men also had higher
      intakes of food groups including meat (P < 0.001), white potatoes (P < 0.05), and
      discretionary oil and solid fat (P < 0.05) and lower intakes of total fruit (P <
      0.05) and milk (P < 0.05). Women did not consume excess nonalcohol kilocalories
      but had higher intakes of total fat (P < 0.05), monounsaturated fat (P < 0.05),
      polyunsaturated fat (P < 0.05), potassium (P < 0.01), and discretionary oil and
      solid fat (P < 0.05) and lower intakes of milk (P < 0.01) and milk products (P <
      0.01). CONCLUSIONS: These mostly moderate drinkers had poorer diets on drinking
      days. Same-day associations between alcohol and diet could be useful targets for
      public health efforts to improve dietary intake.

PMID- 23535110
TI  - Do omega-3 fats boost brain function in adults? Are we any closer to an answer?

PMID- 23535111
TI  - Differential identification of atypical pneumonia pathogens in aorta and internal
      mammary artery related to ankle brachial index and walking distance.
AB  - BACKGROUND: We studied the existence of agents in aorta biopsies, such as
      Chlamydia pneumoniae, cytomegalovirus, and Mycoplasma pneumoniae, that are
      thought to have a role in atherosclerosis etiopathogenesis role, and their
      association with peripheral artery disease. MATERIALS AND METHODS: We examined
      aorta wall and internal mammarian artery (IMA) biopsies taken from two different
      places in 63 patients in whom coronary artery bypass was performed. In these
      biopsies, we evaluated the deoxyribonuclease (DNA) of these microorganisms using
      polymerase chain reaction. From the same patients, we recorded the ankle brachial
      index, road walking distance information, lipid profile, C-reactive proteins,
      blood parameters such as fibrinogen, and the patient's operation data. RESULTS:
      In the nine aorta biopsies taken from 63 patients, we isolated C pneumoniae DNA.
      In IMA biopsies taken from the same patients, we detected no microorganism DNA (P
      < 0.001). In the same aorta biopsies, we found no cytomegalovirus or M pneumoniae
      DNA. We examined 12 patients using an index value of 0.9 in the ankle brachial
      index evaluation; eight had C pneumoniae in the aorta biopsies (P < 0.001).
      CONCLUSIONS: We found a significant relationship between C pneumoniae DNA and the
      existence of peripheral artery disease. In the development of atherosclerosis
      with C pneumoniae, there may be a determinant pathogen in both the aorta and the
      peripheral arteries. The nonexistence of C pneumoniae DNA in the IMA biopsies may
      indicate infectious agents because of the predominant endothelial functions in
      this artery, and thus its resistance to atherosclerosis.

PMID- 23535112
TI  - Surgeon-performed ultrasound predictors of malignancy in patients with Hurthle
      cell neoplasms of the thyroid.
AB  - BACKGROUND: Fine-needle aspiration cannot reliably determine malignancy in
      patients with Hurthle cell neoplasms (HCNs) of the thyroid. Thyroid nodule size
      and characteristics determined by surgeon-performed ultrasound (SUS) may be
      useful for predicting malignancy in HCN preoperatively. This study examined
      whether tumor size and features by SUS can reliably predict malignancy in
      patients with HCN. MATERIALS AND METHODS: We performed a retrospective review of
      84 patients with HCN by fine-needle aspiration, who underwent SUS and
      thyroidectomy from 2002 to 2010. All patients underwent thyroid lobectomy with
      isthmusectomy unless there was a history of radiation exposure, familial thyroid
      cancer, obstructive symptoms, bilateral nodules, and/or patient preference, in
      which case total thyroidectomy was performed. Tumor size and malignant features
      by SUS were correlated with final histopathology using multivariate regression
      analysis. RESULTS: On final histopathology, 29 patients had malignant thyroid
      nodules and 55 patients had benign ones. There were no statistically significant
      differences in terms of age, race, ethnicity, or gender between HCN patients who
      revealed malignant or benign nodules on final pathology. Tumor size >= 4 cm
      measured by SUS did not predict malignancy in HCN. Hypoechogenicity and
      hyperechogenicity were significantly associated with malignancy, whereas
      isoechogenicity was predictive of benignity (P = 0.044). No other
      ultrasonographic features were predictive for thyroid carcinoma by multivariate
      analysis. CONCLUSIONS: Tumor size and features determined by SUS do not reliably
      predict malignancy in patients with HCN. Such patients at risk for malignancy
      should initially undergo thyroid lobectomy for definitive diagnosis.

PMID- 23535113
TI  - Which side of lateral ventricles to choose during external ventricular drainage
      in patients with intraventricular hemorrhage: ipsilateral or contralateral?
AB  - BACKGROUND: We attempted to investigate the effect of external ventricular
      drainage (EVD) plus intraventricular fibrinolysis from ipsilateral or
      contralateral ventricle on clinical outcomes in patients with intraventricular
      hemorrhage. METHODS: We undertook a prospective controlled study. Patients with
      acute obstructive hydrocephalus after intraventricular hemorrhage were randomized
      to receive EVD from ipsilateral ventricle (ipsilateral group [IG]) or
      contralateral ventricle (contralateral group [CG]). They received intracranial
      pressure (ICP) monitoring and intraventricular injection of urokinase after
      surgery. We compared clinical outcomes and complications between groups. RESULTS:
      A total of 45 patients were enrolled, with a mean age of 55.4 years. We assigned
      28 patients assigned to the IG and 17 patients to the CG. Patients in the IG
      showed significantly faster clot clearance in the third and fourth ventricles on
      computed tomography than those in the CG (3.3 +/- 1.0 d versus 3.9 +/- 0.8 d; P =
      0.042). Analysis of ICP data showed that initial ICP in the IG was significantly
      higher than in the CG (20.4 +/- 7.2 mm Hg versus 16.5 +/- 4.4 mm Hg; P = 0.039),
      as was the average daily ICP on the following 3 d. The percentage of ICP readings
      over 20 mm Hg in the IG was also significantly larger than that in the CG (18.0%
      versus 10.9%; P < 0.001). There was no significant difference in the incidence of
      complications regarding rebleeding, infection, epilepsy, or communicating
      hydrocephalus. Neither 30-d mortality rate nor Glasgow Outcome Scale score
      revealed significant differences between the two groups. CONCLUSIONS: External
      ventricular drainage plus EVT from the ipsilateral or contralateral ventricle has
      similar short-term outcomes and complications in patients with intraventricular
      hemorrhage. Faster clot clearance in the third and fourth ventricles but higher
      ICP levels at the early stage may be expected in patients with EVD from the
      ipsilateral ventricle, compared with those from with EVD from the contralateral
      ventricle.

PMID- 23535114
TI  - Development of a bone nonunion in a noncritical segmental tibia defect model in
      sheep utilizing interlocking nail as an internal fixation system.
AB  - BACKGROUND: The bone nonunion is an important complication of bone fracture
      repair. The existing models developed on small animal species prevent using
      osteosynthesis materials designed to be implanted in human bones. The goal of
      this study was to develop a nonunion process in a noncritical segmental tibial
      defect in sheep, a species analogous in size to humans. MATERIALS AND METHODS:
      The animals were divided into two groups of four animals each. In Group 1
      (experimental), the defect was created by surgically stripping the periosteum
      from the edges of a distal tibial osteotomy, keeping the edges 5 mm apart, and
      placing an incomplete O-shaped silicone ring in the gap. Group 2 (control) was
      intervened with a simple fracture at the distal end of the tibia. In both groups
      an interlocking nail was used as a fixation system. Over 8 wk after surgery,
      radiographs and histologic and histomorphometric analyses were performed.
      RESULTS: The control group showed a typical bone repair process. In contrast, the
      experimental group showed a fracture line with rounded edges and a scarce callus
      formation. The bone callus showed reduced amount of bone formation and large
      content of fibrous tissue (P=0.001). CONCLUSIONS: These results indicate that our
      model developed an atrophic nonunion in sheep, a species having multiple
      similarities to humans, such as weight, size, bone structure, and bone remodeling
      process.

PMID- 23535115
TI  - Editorial to accompany "A pilot study of the use of kaolin-impregnated gauze
      (Combat Gauze) for packing high-grade hepatic injuries in a hypothermic
      coagulopathic swine model".

PMID- 23535116
TI  - Profiling the gastrointestinal microbiota in response to Salmonella: low versus
      high Salmonella shedding in the natural porcine host.
AB  - Controlling Salmonella in the food chain is complicated by the ability of
      Salmonella to colonize livestock without causing clinical symptoms/disease.
      Salmonella-carrier animals are a significant reservoir for contamination of naive
      animals, the environment, and our food supply. Salmonella carriage and shedding
      in pigs varies greatly both experimentally and on-farm. To investigate the
      dynamics between the porcine intestinal microbiota and Salmonella shedding, we
      temporally profiled the microbiota of pigs retrospectively classified as low and
      high Salmonella-shedders. Fifty-four piglets were collectively housed, fed and
      challenged with 10(9)Salmonella enterica serovar Typhimurium. Bacterial
      quantitation of Salmonella in swine feces was determined, and total fecal DNA was
      isolated for 16S rRNA gene sequencing from groups of high-shedder, low-shedder,
      and non-inoculated pigs (n=5/group; 15 pigs total). Analyses of bacterial
      community structures revealed significant differences between the microbiota of
      high-shedder and low-shedder pigs before inoculation and at 2 and 7 days post
      inoculation (d.p.i.); microbiota differences were not detected between low
      shedder and non-inoculated pigs. Because the microbiota composition prior to
      Salmonella challenge may influence future shedding status, the "will-be" high and
      low shedder phylotypes were compared, revealing higher abundance of the
      Ruminococcaceae family in the "will-be" low shedders. At 2d.p.i., a significant
      difference in evenness for the high shedder microbiota compared to the other two
      groups was driven by decreases in Prevotella abundance and increases in various
      genera (e.g. Catenibacterium, Xylanibacter). By 21 d.p.i., the microbial
      communities of high-shedder and low-shedder pigs were no longer significantly
      different from one another, but were both significantly different from non
      inoculated pigs, suggesting a similar Salmonella-induced alteration in maturation
      of the swine intestinal microbiota regardless of shedding status. Our results
      correlate microbial shifts with Salmonella shedding status in pigs, further
      defining the complex interactions among the host, pathogen, and microbiota of
      this important public health issue and food safety concern.

PMID- 23535117
TI  - Comparisons of the chondroitin sulphate levels in orthodontically moved canines
      and the clinical outcomes between two different force magnitudes.
AB  - The aims of this study were to compare the chondroitin sulphate (CS) levels in
      gingival crevicular fluid (GCF) of moved canines using either 70 or 120 g of
      orthodontic force, and to compare the rate of tooth movement and the amount of
      pain between these two force magnitudes. Sixteen patients (6 males and 10
      females; aged 16.91 +/- 2.99 years), with class I malocclusion, who required
      orthodontic treatment with first premolar extractions, were recruited. The force
      magnitudes used to move the maxillary canines distally were controlled at 70 and
      120 g on the right and the left sides, respectively. GCF samples were collected
      with Periopaper((r)) strips before and during orthodontic tooth movement.
      Competitive ELISA with monoclonal antibody was used to measure the CS levels. The
      distance of tooth movement and the amount of pain assessed by visual analog scale
      (VAS) scores were evaluated. The medians of CS levels during the loaded period
      were significantly greater than those during the unloaded period (P < 0.05). The
      differences between the medians of CS levels of 70 g and 120 g retraction force
      during each 1 week period were not significant. There was no significant
      difference in the rates of canine movement between these two force magnitudes.
      However, using 120 g, the medians of VAS scores were significantly greater than
      those with 70 g (P < 0.05). Collectively, 70 g retraction force appears to be
      sufficient and more suitable than 120 g force as it causes no difference in
      biochemically-assessed bone remodelling activity, the same rate of tooth
      movement, reduced pain and better comfort.

PMID- 23535118
TI  - Feasibility study of nonclinical safety assessments on homeopathic preparations
      using the example of protoanemonin in Pulsatilla pratensis L.
AB  - Homeopathy is a world-wide available form of complementary therapy, which has a
      tradition of 200years. Due to the long history of clinical use, i.e. reflected by
      the first edition of the Homeopathic Pharmacopoeia of the US of 1914, the conduct
      of toxicological studies is not required if the safety has been otherwise
      substantiated. The aim of this article is to establish a risk assessment
      procedure without full toxicological examination, using homeopathic preparations
      from Pulsatilla pratensis L. as an example. The literature review shows that
      protoanemonin is the most relevant constituent of these plants regarding
      potential toxicity. Based on structural alerts protoanemonin is classified as a
      Cramer class III compound with the threshold of toxicological concern (TTC) of
      180MUg/day in adults. Neither computer aided toxicology methods (Toxtree and
      Derek Nexus(r)) nor a literature search revealed any evidence of genotoxic,
      carcinogenic or teratogenic potential of protoanemonin. The protoanemonin
      exposure from a maximum daily dose of a typical homeopathic preparation of P.
      pratensis L. does not exceed the TTC. The presented method is transparent,
      reproducible and applicable to other homeopathic substances as a use-case
      scenario for computational toxicology in order to evaluate an approach for safety
      assessment of homeopathic medicinal products.

PMID- 23535119
TI  - Case study illustrating the WHO IPCS guidance on characterization and application
      of physiologically based pharmacokinetic models in risk assessment.
AB  - The World Health Organization (WHO) International Programme on Chemical Safety
      (IPCS) Guidance on Characterization and Application of Physiologically Based
      Pharmacokinetic Models in Risk Assessment (IPCS, 2010) describes key principles
      for risk assessors and model developers. In the WHO Guidance, a template for
      model documentation was developed and a case study included. Here the WHO
      Guidance, including the template, is summarized and an additional case study is
      presented to illustrate its application, based upon an existing risk assessment
      for 2-butoxyethanol (CAS NO. 111-76-2). The goal of the WHO Guidance and the
      current paper is to increase regulatory acceptance of complex biologically
      descriptive pharmacokinetic (or toxicokinetic) models, such as PBPK models, by
      facilitating communication and successful interaction between modelers and risk
      assessors.

PMID- 23535120
TI  - The Medicine of the Manuka: an investigation of the usages and methods for
      utilization of honey derived from the pollen of Leptospermum scoparium in
      holistic nursing practice.
AB  - As nursing moves into the next paradigm of health care, there is an increasing
      shift toward integrative health care that is founded on the integration of
      traditional or complementary medicines alongside biomedicine. As part of the
      shift nurses are increasingly observing clients accessing traditional forms of
      medicine. One such product that has been used for hundreds of years and is more
      recently being incorporated into nursing care is the honey produced by bees
      pollinating Leptospermum scoparium, traditionally known as Manuka. Manuka honey
      is currently used widely in wound care and as a topical antibacterial,
      antifungal, and anti-inflammatory. Review of the literature supports a very
      effective and low-risk botanical intervention that is both cost-effective and
      easily accessible. There is future scope for the use of L. scoparium oil products
      in nursing and potential for further research to continue to discover its
      effectiveness. 

PMID- 23535121
TI  - Identification of perivascular adipose tissue in the mouse skin using two-photon
      microscopy.

PMID- 23535122
TI  - A busy time for science editors.

PMID- 23535123
TI  - Global health--multiple definitions, single goal.
AB  - Although there is a wealth of research on and attention of both the public and
      the researchers about global health, there is still some controversy and
      uncertainty about the real meaning of the term "global health". In a
      multidisciplinary and intersectorial field such as global health, common
      definition is important for clear and effective communication among all involved
      in global health.

PMID- 23535124
TI  - On the paradoxes of informed consent: strictness with unlikely risks, tolerance
      with certain harm.
AB  - The different approaches of two nations to the issues surrounding informed
      consent by persons with no or limited capacity of understanding are compared. It
      is important that efforts to ensure formal compliance with consent procedures
      should not be allowed to distract attention from the risks of harm to
      individuals.

PMID- 23535126
TI  - A geoprocessing model for the selection of populations most affected by diffuse
      industrial contamination: the case of oil refinery plants.
AB  - INTRODUCTION: A method to select populations living in areas affected by diffuse
      environmental contamination is presented, with particular regard to oil
      refineries, in the Italian context. The reasons to use municipality instead of
      census tract populations for environment and health small-area studies of
      contaminated sites are discussed. METHODS: Populations most affected by diffuse
      environmental contamination are identified through a geoprocessing model. Data
      from the national census 2001 were used to estimate census tract level
      populations. A geodatabase was developed using the municipality and census tract
      layers provided by the Italian National Bureau of Statistics (ISTAT). The
      orthophotos of the Italian territory - year 2006 - available on the geographic
      information systems (GIS) of the National Cartographic Portal, were considered.
      The area within 2 km from the plant border was used as an operational definition
      to identify the area at major contamination. RESULTS: The geoprocessing model
      architecture is presented. The results of its application to the selection of
      municipality populations in a case study are shown. CONCLUSIONS: The application
      of the proposed geoprocessing model, the availability of long time series of
      mortality and morbidity data, and a quali-quantitative estimate of contamination
      over time, could allow an appraisal of the health status of populations affected
      by oil refinery emissions.

PMID- 23535125
TI  - Invertebrate welfare: an overlooked issue.
AB  - While invertebrates make up the majority of animal species, their welfare is
      overlooked compared to the concern shown to vertebrates. This fact is highlighted
      by the near absence of regulations in animal research, with the exception of
      cephalopods in the European Union. This is often justified by assumptions that
      invertebrates do not experience pain and stress while lacking the capacity for
      higher order cognitive functions. Recent research suggests that invertebrates may
      be just as capable as vertebrates in experiencing pain and stress, and some
      species display comparable cognitive capacities. Another obstacle is the negative
      view of invertebrates by the public, which often regards them as pests with no
      individual personalities, gastronomic entities, or individuals for scientific
      experimentation without rules. Increasingly, studies have revealed that
      invertebrates possess individual profiles comparable to the personalities found
      in vertebrates. Given the large economic impact of invertebrates, developing
      certain attitude changes in invertebrate welfare may be beneficial for producers
      while providing higher welfare conditions for the animals. While the immense
      number and type of species makes it difficult to suggest that all invertebrates
      will benefit from increased welfare, in this review we provide evidence that the
      topic of invertebrate welfare should be revisited, more thoroughly investigated,
      and in cases where appropriate, formally instituted.

PMID- 23535127
TI  - Human biomonitoring for Cd, Hg and Pb in blood of inhabitants of the Sacco Valley
      (Italy).
AB  - INTRODUCTION: The Sacco Valley (Lazio, Italy) is characterized by high density
      population and several industrial chemical productions that during the time had
      led to a substantial amount of by-products. The result was a severe environmental
      pollution of the area and in particular of the river Sacco. In 1991, the analysis
      of water and soils samples of three industrial landfills revealed the presence of
      organochlorine compounds and heavy metals. A research project named "Health of
      residents living in Sacco Valley area", coordinated by the regional Department of
      Epidemiology, was undertaken and financed to evaluate the state of health of the
      population living near those polluted areas. MATERIALS AND METHODS: Cd, Hg and Pb
      were quantified in 246 blood samples of potentially exposed residents of the
      Sacco Valley by quadrupole inductively coupled plasma mass spectrometry (Q-ICP
      MS). RESULTS: Individuals who agreed to be sampled did not exhibit high levels of
      the elements. The distance from the river does not seem to be directly connected
      with the elements levels in blood. The contribution of these contaminants to the
      total intake due to ingestion of food was difficult to evaluate. The unclear
      trend of data would require a characterization of the polluted site with
      environmental sampling of different matrices.

PMID- 23535128
TI  - A home assistance model for dementia: outcome in patients with mild-to-moderate
      Alzheimer's disease after three months.
AB  - The treatment of dementias, which are currently incurable pathologies, requires
      an approach to care that involves both the patients and their families. The
      effect of alternative interventions, besides the pharmacological approach,
      therefore warrants evaluation. In this paper, we describe one such intervention,
      which was provided by our home care team for Alzheimer's Disease. Patients were
      granted a three-month period of home care assistance, which included physical and
      cognitive rehabilitation as well as interventions on the home environment and the
      family, such as psychological support for the main caregivers. The assistance was
      provided in thrice-weekly sessions, each lasting six hours. Twenty-two patients
      (age 78.4+/-6.5 yrs), all of whom had received a diagnosis of probable AD, were
      enrolled. There was a statistically significant improvement in the NPI score (p =
      0.004), Barthel index (p = 0.01), Tinetti's scale (p = 0.013) and CBI score (p =
      0.016) at the end of the 3-month treatment period. The patients' caregivers also
      reported a significant improvement in the physical and social burden at the CBI
      at the end of the period of home care assistance (p = 0.026 and p = 0.006). In a
      further evaluation performed 3 months after the end of the treatment period, the
      beneficial effect previously observed in both patients and caregivers was no
      longer present.

PMID- 23535129
TI  - Pharmaco-epidemiological description of the population of the Marche Region
      (central Italy) treated with the antipsychotic drug olanzapine.
AB  - BACKGROUND: In Italy, even though olanzapine has been discouraged for treatment
      of behaviour disorders in older patients affected by dementia, some physicians
      chose to prescribe for them. In response to this situation, the Italian Drug
      Agency (Agenzia Italiana del Farmaco, AIFA) promulgated a cautionary note.
      MATERIALS AND METHODS: This study examined epidemiological indices for olanzapine
      prescriptions between 2004 and 2007 in the Marche Region of central Italy and in
      its provinces, to assess physician compliance with the AIFA note, and to
      determine whether there were differences in drug prescription between populations
      of the same territory, or differences based on gender or age group. RESULTS: Our
      analyses revealed high olanzapine use among young men and mature women,
      suggesting that these groups are most prone to psychotic symptoms. Analysis
      revealed that olanzapine prescription in elderly patients was reduced in some
      provinces, in line with the AIFA note. CONCLUSIONS: Prudent use of olanzapine
      prescription, in compliance with the AIFA note, was noted throughout the Region.
      Furthermore, this work offers details that may be useful in future studies of
      adverse drug reactions.

PMID- 23535130
TI  - Molecular epidemiology of measles virus in Italy during 2008.
AB  - INTRODUCTION: 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. A large
      measles outbreak occurred in Italy in 2008, with over 4000 cases reported to the
      enhanced measles surveillance system introduced in 2007, 37% of which were
      laboratory confirmed. METHODS: Urine and saliva samples were collected during
      2008. A phylogenetic analysis of measles sequences was performed in order to
      understand the epidemiological situation of wild-type (MV) circulation in that
      period. RESULT AND DISCUSSION: Data showed predominant circulation of the
      genotype D4. Genotypes A, D8, D9 and H1 were also detected in a small number of
      samples, probably representing imported cases.

PMID- 23535131
TI  - Medical humanities in healthcare education in Italy: a literature review.
AB  - OBJECTIVE: The introduction of medical humanities (MH) in undergraduate medical
      education in Italy has been an issue of debate since the 90's and few years later
      it was extended to other healthcare degrees. The aims of this Italian literature
      review, after considering the international scene, are: to evaluate the extent to
      which the interest in this subject has gradually developed throughout the
      country; which professional groups have contributed to the debate; to identify
      which theoretical constructs led to the introduction of MH in undergraduate
      medical education; to identify whether a clear and shared definition of MH exists
      in Italian literature; to verify what kinds of MH experiences have been
      accomplished in Italy. MATERIALS AND METHODS: A comprehensive literature search
      was conducted, including electronic databases, bibliographies, manual sorting of
      articles in paper format, congress proceedings. RESULTS: The analysis of the
      chosen articles underlines that, however limited, Italian literature does not
      present a very different picture from the international scene. It emerges that
      teaching MH is believed to be an important feature in undergraduate education of
      healthcare professionals who intend to propose a bio-psychological-social
      approach to care, in spite of the difficulty to measure its short and long term
      effectiveness. The lack of a multidisciplinary, multi-professional approach is
      also evident. CONCLUSION: Further research aiming to implement the quantity and
      quality of MH studies in the curricula of undergraduate healthcare education is
      desirable.

PMID- 23535132
TI  - Blood thiamine, zinc, selenium, lead and oxidative stress in a population of male
      and female alcoholics: clinical evidence and gender differences.
AB  - INTRODUCTION: Long term alcohol abuse is associated with deficiencies in
      essential nutrients and minerals that can cause a variety of medical consequences
      including accumulation of toxic metals. AIM: The aim of this research is to get
      evidence-based data to evaluate alcohol damage and to optimize treatment.
      Thiamine and thiamine diphosphate (T/TDP), zinc (Zn), selenium (Se), lead (Pb)
      and oxidative stress in terms of reactive oxygen metabolites (ROMs) were examined
      in blood samples from 58 alcohol dependent patients (17 females and 41 males).
      RESULTS: T/TDP concentration in alcoholics resulted significantly lower than
      controls (p < 0.005) for both sexes. Serum Zn and Se did not significantly differ
      from reference values. Levels of blood Pb in alcoholics resulted significantly
      higher (p < 0.0001) than Italian reference values and were higher in females than
      in males. ROMs concentration was significantly higher than healthy population
      only in female abusers (p = 0.005). CONCLUSION: Alcoholics show a significant
      increase in blood oxidative stress and Pb and decrease in thiamine. Impairment
      occurs mainly in female abusers confirming a gender specific vulnerability.

PMID- 23535133
TI  - Advancing the science of cancer cost measurement: challenges and opportunities.
AB  - OBJECTIVES: Cancer accounts for a major proportion of national health
      expenditures, which are expected to increase in the future. This paper aims to
      identify major challenges with estimating cancer related costs, and discuss
      international comparisons, and recommendations for future research. METHODS: It
      starts from the experience of an international workshop aimed at comparing cancer
      burden evaluation methods, improving results comparability, discussing strengths
      and criticisms of different approaches. RESULTS: Three methodological themes
      necessary to inform the analysis are identified and discussed: data availability;
      costs definition; epidemiological measures. CONCLUSIONS: Cost evaluation is
      applied to cancer control interventions and is relevant for public health
      planners. Despite their complexity, international comparisons are fundamental to
      improve, generalize and extend cost evaluation to different contexts.

PMID- 23535134
TI  - Validation of the Italian version of the Screening Questionnaire for Disaster
      Mental Health (SQD) in a post-earthquake urban environment.
AB  - INTRODUCTION: Aim of this study was to implement and validate the Italian version
      of the Screening Questionnaire for Disaster Mental Health (SQD), a tool for the
      screening of post-traumatic stress disorder (PTSD) and depression in the long
      term aftermaths of a natural disaster. METHODS: A convenience sample of 116
      subjects living in L'Aquila after the 2009 earthquake were administered the SQD
      and two gold-standard instruments for PTSD and depression. Reliability,
      concurrent validity and convergent validity of SQD were estimated. RESULTS:
      Cronbach's alpha was 0.86. Concurrent validity as measured by the Spearman
      correlation coefficient resulted statistically significant both for PTSD and
      depression SQD subscales, as well as convergent validity as measured by ROC-AUC
      method. CONCLUSIONS: SQD is a valid, efficient and easy-to-use screening
      instrument for PTSD and depression after natural disasters.

PMID- 23535135
TI  - A student manual for promoting mental health among high school students.
AB  - OBJECTIVES: We describe a school program based on a student manual for promoting
      mental health and preventing mental illness. METHODS: A preliminary version of
      the manual was assessed for face validity by two focus groups. The final version
      was evaluated for acceptability among 253 students in 10 high schools and 1
      middle school in Italy. RESULTS: The manual included 18 chapters (or "units")
      which address skills for enabling students to cope with their daily lives:
      communication skills, problem-solving, assertive skills, negotiation, stress
      management, anger management and conflict resolution. The manual was found to
      have been acceptable by high school students. CONCLUSIONS: The effectiveness of
      the manual in actually promoting mental health and preventing mental illness is
      currently being evaluated.

PMID- 23535136
TI  - Medical progress, psychological factors and global care of the patient: lessons
      from the treatment of childhood leukemia.
AB  - The history of treatment of childhood leukemia is a meaningful model of ethical,
      bioethical and organizational repercussions of medical progress. Specifically, it
      has provided precious indications and very useful tools to cope with several of
      the more important problems of modern medicine: the value of controlled
      randomized studies; the risks of intense medicalization impairing the quality of
      care; the importance of a valid doctor-patient relationship; the psycho-emotive
      involvement of the pediatric staff; and last but not least, the need of an
      unrelenting effort of humanization of the procedures and environments, hand in
      hand with the frequent adjustments of the protocols according to scientific and
      technological progress. Finally, the authors comment upon the first cures (1962
      1966) observed in the Pediatrics Clinic of the Sapienza University of Rome.

PMID- 23535137
TI  - Dihydropyridine calcium channel blockers inhibit non-esterified-fatty-acid
      induced endothelial and rheological dysfunction.
AB  - Circulating NEFAs (non-esterified fatty acids) from adipose tissue lipolysis lead
      to endothelial dysfunction and insulin resistance in patients with the metabolic
      syndrome or Type 2 diabetes mellitus. The aim of the present study was to test
      the hypothesis that DHP (dihydropyridine) CCBs (calcium channel blockers) prevent
      NEFA-induced endothelial and haemorheological dysfunction independently of their
      antihypertensive properties. Using a double-blind cross-over study design,
      nifedipine, amlodipine, diltiazem or placebo were administered to eight healthy
      subjects for 2 days before each study day. On the study days, the following were
      assessed before and after the infusion of lipid and heparin to raise serum NEFAs:
      endothelial function, by measuring FBF (forearm blood flow) responses to ACh
      (acetylcholine); leucocyte activation, by ex vivo measurement of plasma MPO
      (myeloperoxidase) levels, adherent leucocyte numbers and whole blood transit time
      through microchannels; and oxidative stress, by determining plasma levels of d
      ROMs (derivatives of reactive oxygen metabolites). Effects of the CCBs on NF
      kappaB (nuclear factor kappaB) p65 phospholylation stimulated by NEFAs were
      assessed in cultured monocytic cells in vitro. Elevated NEFAs reduced the
      responses to ACh and significantly increased whole blood transit time, adherent
      leucocyte numbers and d-ROMs. Nifedipine and amlodipine, but not diltiazem,
      prevented NEFA-induced endothelial dysfunction, leucocyte activation and
      enhancement of oxidative stress without affecting BP (blood pressure), whereas
      all these drugs prevented NEFA-induced p65 activation in vitro. These results
      suggest that DHP CCBs, independent of their antihypertensive properties in
      humans, prevent NEFA-induced endothelial and haemorheological dysfunction through
      inhibition of NEFA-induced leucocyte activation, although the sensitivity to
      drugs of leucocyte Ca2+ channels may differ among cells.

PMID- 23535138
TI  - Flexible synthesis and evaluation of diverse anti-Apicomplexa cyclic peptides.
AB  - A modular approach to synthesize anti-Apicomplexa parasite inhibitors was
      developed that takes advantage of a pluripotent cyclic tetrapeptide scaffold
      capable of adjusting appendage and skeletal diversities in only a few steps (one
      to three steps). The diversification processes make use of selective radical
      coupling reactions and involve a new example of a reductive carbon-nitrogen
      cleavage reaction with SmI2. The resulting bioactive cyclic peptides have
      revealed new insights into structural factors that govern selectivity between
      Apicomplexa parasites such as Toxoplasma and Plasmodium and human cells.

PMID- 23535139
TI  - Transcriptomic and cellular response to bacterial challenge (pathogenic Vibrio
      parahaemolyticus) in farmed juvenile Haliotis rufescens fed with or without
      probiotic diet.
AB  - The abalone production in Chile has increased considerably in recent years with
      no sign of tapering off. Open and semi-closed circuits in the marine water zones
      in the north and south of Chile are the preferred areas of culture. Coastal
      ecosystems are subjected to a wide variety of contaminants that generate stress
      that affects populations via their impacts to individuals at both physiological
      and genetic levels. This work investigated the genomic and cellular response of
      post-weaning juvenile Haliotis rufescens abalone under hatchery conditions, fed
      with probiotic diets, and subsequently challenged with Vibrio parahaemolyticus.
      The expression patterns of 16 selected genes associated with different metabolic
      pathways were analyzed using Real-Time PCR. Gene expression was then compared to
      immunological response parameters in the abalone and quantification of V.
      parahaemolyticus during the experimental period. Both transcriptomic and
      immunological analyses indicated significant alteration of physiological
      processes in H. rufescens correlated to exposure to the pathogenic bacteria, as
      well as to probiotic nutrition.

PMID- 23535141
TI  - Adaptation and modification of three CRISPR loci in two closely related
      cyanobacteria.
AB  - An RNA-based screen was performed to reveal a possible evolutionary scenario for
      the CRISPR-Cas systems in two cyanobacterial model strains. Following the
      analysis of a draft genome sequence of Synechocystis sp PCC6714, three different
      CRISPR-Cas systems were characterized that have different degrees of relatedness
      to another three CRISPR-Cas systems in Synechocystis sp PCC6803. A subtype III-B
      system was identified that is extremely conserved between both strains. Strong
      signals in northern hybridizations and the presence of different spacers (but
      identical repeats) indicated this system to be active, despite the absence of a
      known endonuclease candidate gene involved in the maturation of its crRNAs in the
      two strains. The other two systems were found to differ significantly from each
      other, with different sets of repeat-spacer arrays and different Cas genes. In
      view of the otherwise very close relatedness of the two analyzed strains, this is
      suggestive of an unknown mechanism involved in the replacement of CRISPR-Cas
      cassettes as a whole. Further RNA analyses revealed the accumulation of crRNAs to
      be impacted by environmental conditions critical for photoautotropic growth. All
      six systems are associated with a gene for a possible transcriptional repressor.
      Indeed, we identified one of these genes, sll7009, as encoding a negative
      regulator specific for the CRISPR1 subtype I-D system in Synechocystis sp
      PCC6803. 

PMID- 23535142
TI  - Frailty in people with COPD, using the National Health and Nutrition Evaluation
      Survey dataset (2003-2006).
AB  - BACKGROUND: Little is known about frailty in people with chronic obstructive
      pulmonary disease (COPD). The purposes of this study were to describe frailty, to
      identify, which demographic and clinical characteristics contributed to frailty,
      and to examine the relationship between frailty and health-related outcomes in
      people with COPD. METHODS: This was a secondary cross-sectional study, using data
      from the National Health and Nutrition Evaluation Survey. The frailty index and
      outcome measures were derived primarily from survey responses. RESULTS: The
      prevalence of frailty was 57.8%. Multivariate logistic regression showed that
      individuals with COPD who had self-reported shortness of breath and comorbid
      diabetes were more likely to be frail than those who did not. Frail people tended
      to have a greater number of disabilities. CONCLUSIONS: The findings support the
      importance of frailty in the COPD population. Further study is needed to
      understand frailty in people with COPD, using objective measures for criteria of
      frailty.

PMID- 23535140
TI  - Structure activity relationship of synaptic and junctional neurotransmission.
AB  - Chemical neurotransmission may include transmission to local or remote sites.
      Locally, contact between 'bare' portions of the bulbous nerve terminal termed a
      varicosity and the effector cell may be in the form of either synapse or non
      synaptic contact. Traditionally, all local transmissions between nerves and
      effector cells are considered synaptic in nature. This is particularly true for
      communication between neurons. However, communication between nerves and other
      effectors such as smooth muscles has been described as nonsynaptic or junctional
      in nature. Nonsynaptic neurotransmission is now also increasingly recognized in
      the CNS. This review focuses on the relationship between structure and function
      that orchestrate synaptic and junctional neurotransmissions. A synapse is a
      specialized focal contact between the presynaptic active zone capable of
      ultrafast release of soluble transmitters and the postsynaptic density that
      cluster ionotropic receptors. The presynaptic and the postsynaptic areas are
      separated by the 'closed' synaptic cavity. The physiological hallmark of the
      synapse is ultrafast postsynaptic potentials lasting milliseconds. In contrast,
      junctions are juxtapositions of nerve terminals and the effector cells without
      clear synaptic specializations and the junctional space is 'open' to the
      extracellular space. Based on the nature of the transmitters, postjunctional
      receptors and their separation from the release sites, the junctions can be
      divided into 'close' and 'wide' junctions. Functionally, the 'close' and the
      'wide' junctions can be distinguished by postjunctional potentials lasting ~1s
      and tens of seconds, respectively. Both synaptic and junctional communications
      are common between neurons; however, junctional transmission is the rule at many
      neuro-non-neural effectors.

PMID- 23535143
TI  - Reconstitution of recombination-associated DNA synthesis with human proteins.
AB  - The repair of DNA breaks by homologous recombination is a high-fidelity process,
      necessary for the maintenance of genome integrity. Thus, DNA synthesis associated
      with recombinational repair must be largely error-free. In this report, we show
      that human DNA polymerase delta (delta) is capable of robust DNA synthesis at
      RAD51-mediated recombination intermediates dependent on the processivity clamp
      PCNA. Translesion synthesis polymerase eta (eta) also extends these substrates,
      albeit far less processively. The single-stranded DNA binding protein RPA
      facilitates recombination-mediated DNA synthesis by increasing the efficiency of
      primer utilization, preventing polymerase stalling at specific sequence contexts,
      and overcoming polymerase stalling caused by topological constraint allowing the
      transition to a migrating D-loop. Our results support a model whereby the high
      fidelity replicative DNA polymerase delta performs recombination-associated DNA
      synthesis, with translesion synthesis polymerases providing a supportive role as
      in normal replication.

PMID- 23535144
TI  - AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system.
AB  - AGO/RISC-mediated antiviral RNA silencing, an important component of the plant's
      immune response against RNA virus infections, was recapitulated in vitro.
      Cytoplasmic extracts of tobacco protoplasts were applied that supported
      Tombusvirus RNA replication, as well as the formation of RNA-induced silencing
      complexes (RISC) that could be functionally reconstituted with various plant
      ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were
      programmed with exogenous siRNAs that specifically targeted the viral RNA,
      endonucleolytic cleavages occurred and viral replication was inhibited. Antiviral
      RNA silencing was disabled by the viral silencing suppressor p19 when this was
      present early during RISC formation. Notably, with replicating viral RNA, only
      (+)RNA molecules were accessible to RISC, whereas (-)RNA replication
      intermediates were not. The vulnerability of viral RNAs to RISC activity also
      depended on the RNA structure of the target sequence. This was most evident when
      we characterized viral siRNAs (vsiRNAs) that were particularly effective in
      silencing with AGO1- or AGO2/RISC. These vsiRNAs targeted similar sites,
      suggesting that accessible parts of the viral (+)RNA may be collectively attacked
      by different AGO/RISC. The in vitro system was, hence, established as a valuable
      tool to define and characterize individual molecular determinants of antiviral
      RNA silencing.

PMID- 23535145
TI  - Dissection of cell cycle-dependent dynamics of Dnmt1 by FRAP and diffusion
      coupled modeling.
AB  - DNA methyltransferase 1 (Dnmt1) reestablishes methylation of hemimethylated CpG
      sites generated during DNA replication in mammalian cells. Two subdomains, the
      proliferating cell nuclear antigen (PCNA)-binding domain (PBD) and the targeting
      sequence (TS) domain, target Dnmt1 to the replication sites in S phase. We aimed
      to dissect the details of the cell cycle-dependent coordinated activity of both
      domains. To that end, we combined super-resolution 3D-structured illumination
      microscopy and fluorescence recovery after photobleaching (FRAP) experiments of
      GFP-Dnmt1 wild type and mutant constructs in somatic mouse cells. To interpret
      the differences in FRAP kinetics, we refined existing data analysis and modeling
      approaches to (i) account for the heterogeneous and variable distribution of
      Dnmt1-binding sites in different cell cycle stages; (ii) allow diffusion-coupled
      dynamics; (iii) accommodate multiple binding classes. We find that transient PBD
      dependent interaction directly at replication sites is the predominant specific
      interaction in early S phase (residence time Tres <= 10 s). In late S phase, this
      binding class is taken over by a substantially stronger (Tres ~22 s) TS domain
      dependent interaction at PCNA-enriched replication sites and at nearby
      pericentromeric heterochromatin subregions. We propose a two-loading-platform
      model of additional PCNA-independent loading at postreplicative, heterochromatic
      Dnmt1 target sites to ensure faithful maintenance of densely methylated genomic
      regions.

PMID- 23535146
TI  - Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the
      presence of the initiator protein RepD.
AB  - The helicase PcrA unwinds DNA during asymmetric replication of plasmids, acting
      with an initiator protein, in our case RepD. Detailed kinetics of PcrA activity
      were measured using bulk solution and a single-molecule imaging technique to
      investigate the oligomeric state of the active helicase complex, its processivity
      and the mechanism of unwinding. By tethering either DNA or PcrA to a microscope
      coverslip surface, unwinding of both linear and natural circular plasmid DNA by
      PcrA/RepD was followed in real-time using total internal reflection fluorescence
      microscopy. Visualization was achieved using a fluorescent single-stranded DNA
      binding protein. The single-molecule data show that PcrA, in combination with
      RepD, can unwind plasmid lengths of DNA in a single run, and that PcrA is active
      as a monomer. Although the average rate of unwinding was similar in single
      molecule and bulk solution assays, the single-molecule experiments revealed a
      wide distribution of unwinding speeds by different molecules. The average rate of
      unwinding was several-fold slower than the PcrA translocation rate on single
      stranded DNA, suggesting that DNA unwinding may proceed via a partially passive
      mechanism. However, the fastest dsDNA unwinding rates measured in the single
      molecule unwinding assays approached the PcrA translocation speed measured on
      ssDNA.

PMID- 23535148
TI  - Seasonal changes in immunoreactivity of inhibin/activin subunits in the
      epididymis of wild ground squirrels (Citellus dauricus Brandt).
AB  - The inhibin/activin subunits (alpha, betaA and betaB) have been found in
      epididymal tissue of many mammals, but there have been no data available for wild
      seasonal breeders so far. The aim of this study was to investigate the
      immunoreactivities of inhibin/activin alpha, betaA and betaB subunits in the
      epididymis of wild ground squirrels during the breeding and nonbreeding seasons.
      Immunohistochemistry and Western blotting were performed to detect the epididymal
      immunolocalizations and immunoreactivities of the three subunits. Strong
      immunostaining of alpha subunit was present in the interstitial part of the caput
      epididymis and epithelial parts of the corpus epididymis and cauda epididymis
      during the breeding season, whereas no alpha subunit was found in the nonbreeding
      season. betaA and betaB subunits were expressed in all cell types of the
      epithelium throughout the whole seasonal cycle, and immunostaining in the
      breeding season was likely stronger compared with that of the nonbreeding season.
      These results suggested that the epididymis might be a potential source of
      inhibin and activin in the wild male ground squirrel, and the secretion of
      epididymal inhibin and activin showed distinct seasonal changes. Furthermore,
      inhibin and activin might function as paracrine and/or autocrine factors that
      have an effect on the epididymis. 

PMID- 23535149
TI  - Quantifying capital goods for waste landfilling.
AB  - Materials and energy used for construction of a hill-type landfill of 4 million
      m(3) were quantified in detail. The landfill is engineered with a liner and
      leachate collections system, as well as a gas collection and control system.
      Gravel and clay were the most common materials used, amounting to approximately
      260 kg per tonne of waste landfilled. The environmental burdens from the
      extraction and manufacturing of the materials used in the landfill, as well as
      from the construction of the landfill, were modelled as potential environmental
      impacts. For example, the potential impact on global warming was 2.5 kg carbon
      dioxide (CO2) equivalents or 0.32 milli person equivalents per tonne of waste.
      The potential impacts from the use of materials and construction of the landfill
      are low-to-insignificant compared with data reported in the literature on impact
      potentials of landfills in operation. The construction of the landfill is only a
      significant contributor to the impact of resource depletion owing to the high use
      of gravel and steel.

PMID- 23535147
TI  - Anesthesia and tau pathology.
AB  - Alzheimer's disease (AD) is the most common form of dementia and remains a
      growing worldwide health problem. As life expectancy continues to increase, the
      number of AD patients presenting for surgery and anesthesia will steadily rise.
      The etiology of sporadic AD is thought to be multifactorial, with environmental,
      biological and genetic factors interacting together to influence AD pathogenesis.
      Recent reports suggest that general anesthetics may be such a factor and may
      contribute to the development and exacerbation of this neurodegenerative
      disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of
      hyperphosphorylated and aggregated tau protein are one of the main
      neuropathological hallmarks of AD. Tau pathology is important in AD as it
      correlates very well with cognitive dysfunction. Lately, several studies have
      begun to elucidate the mechanisms by which anesthetic exposure might affect the
      phosphorylation, aggregation and function of this microtubule-associated protein.
      Here, we specifically review the literature detailing the impact of anesthetic
      administration on aberrant tau hyperphosphorylation as well as the subsequent
      development of neurofibrillary pathology and degeneration. 

PMID- 23535150
TI  - Do patient-perceived pros and cons of opioids predict sustained higher-dose use?
AB  - OBJECTIVES: Chronic opioid therapy (COT) is associated with various adverse
      outcomes, especially at higher doses, yet little is known about predictors of
      sustained higher-dose COT. This study aimed to ascertain, among higher-dose COT
      patients, the association of patient-perceived pros and cons of opioids with
      continued higher-dose use 1 year later. METHODS: Patients (N=1229) in 2 large
      health plans prescribed >=50 mg morphine-equivalent dose (MED) per day for
      chronic noncancer pain completed a survey assessing opioid benefits and harms.
      The Prescribed Opioid Difficulties Scale questionnaire assessed psychosocial
      problems, concerns, benefits, and side effects related to opioid use. Logistic
      regression models estimated the associations of the reported benefits and
      problems with higher-dose continuation (>=50 mg MED/d) versus dose reduction (<50
      mg MED/d) 1 year later. RESULTS: Over 80% of participants continued higher-dose
      opioid use at 1 year, regardless of reported problems, concerns, side effects,
      pain reduction, or perceived helpfulness. Higher scores on the Prescribed Opioid
      Difficulties Scale Problems subscale (odds ratio=0.79, 95% confidence interval,
      0.68-0.92) and Concerns subscale (odds ratio=0.76, 95% confidence interval, 0.65
      0.90) were negatively associated with higher-dose use 1 year later. Other
      baseline measures (opioid helpfulness, reduction in pain, number of side effects,
      and side effect bothersomeness) were not significantly associated with continued
      higher-dose use. DISCUSSION: The large majority of patients continued using
      higher-dose opioids regardless of baseline characteristics. These findings
      suggest the difficulty of reducing opioid dose among chronic higher-dose opioid
      users.

PMID- 23535151
TI  - Recombinant human erythropoietin pretreatment alleviates renal glomerular injury
      induced by cardiopulmonary bypass by reducing transient receptor potential
      channel 6-nuclear factor of activated T-cells pathway activation.
AB  - OBJECTIVE: Acute renal injury after cardiopulmonary bypass is common and
      associated with high mortality. We aimed to demonstrate the glomerular protective
      effects of recombinant human erythropoietin using an in vivo rat cardiopulmonary
      bypass model and to explore the possible mechanism. METHODS: Dose-related renal
      protective effects of recombinant human erythropoietin were studied in phase I.
      Male Sprague Dawley rats were randomly divided into 5 groups: sham group,
      cardiopulmonary bypass group, and 3 recombinant human erythropoietin-treated
      cardiopulmonary bypass groups (bolus doses of 500, 3000, and 5000 U/kg 24 hours
      before surgery). Blood and urine samples were collected just before surgery and
      at 2, 4, 24, 48, and 72 hours after surgery. In phase II, rats were divided into
      3 groups: sham group, cardiopulmonary bypass group, and 5000 U/kg recombinant
      human erythropoietin group. Kidneys were harvested at 4, 24, 48, and 72 hours
      after surgery. Ultra-organization of glomeruli was observed. Glomerular transient
      receptor potential channel 6 (TRPC6) expression was studied by immunofluorescence
      and Western blot. Nuclei nuclear factor of activated T-cells, cytoplasmic,
      calcineurin-dependent 1 (NFATc1) activity was analyzed by enzyme-linked
      immunosorbent assays and electrophoretic mobility shift assay. RESULTS:
      Pretreatment of 5000 U/kg recombinant human erythropoietin decreased the urine
      protein (72 hours: 7.82 +/- 1.13 g/L vs 11.28 +/- 1.73 g/L), serum creatinine (72
      hours: 35.0 +/- 3.5 MUmol/L vs 60.7 +/- 7.6 MUmol/L), and cystatin-C (2 hours:
      336.5 +/- 28.2 MUg/L vs 452.6 +/- 63.8 MUg/L) compared with the control group (P
      < .01). Cardiopulmonary bypass induced morphologic abnormalities of podocyte foot
      processes and slit diaphragms, which was improved by recombinant human
      erythropoietin. Furthermore, recombinant human erythropoietin significantly
      relieved glomerular TRPC6 increase and NFATc1 activation induced by
      cardiopulmonary bypass. CONCLUSIONS: Pretreatment of 5000 U/kg recombinant human
      erythropoietin elicited potent glomerular protection against cardiopulmonary
      bypass. This protection may be partly due to downregulation of glomerular TRPC6
      NFATc1 pathway.

PMID- 23535152
TI  - Clinical impact of neurocognitive deficits after cardiac surgery.
AB  - OBJECTIVES: Postoperative neurocognitive deficits (POCDs) have been found to
      occur frequently after cardiac surgery. Although POCDs have received significant
      attention in the medical literature and public media, the true clinical impact of
      these deficits on patient outcomes and quality of life (QOL) is not well defined.
      METHODS: Neuropsychometric testing was performed on 696 patients undergoing
      coronary artery bypass surgery using a battery of tests divided into 4 domains;
      memory, attention, speed, and psychomotor function. These were performed
      preoperatively, at hospital discharge, and at 3 months postoperatively. POCDs
      were defined as a drop in scores by 1 standard deviation in 1 domain or more. QOL
      was assessed using Short Form 36 and clinical outcomes were recorded. RESULTS:
      POCDs were identified in 265 (38%) patients at discharge and in 132 (19%) at 3
      months. There was no observed difference in mortality or major morbidity in
      patients with or without POCDs. Predictors of POCDs at discharge were elevated
      preoperative creatinine (P = .04), increased cardiopulmonary bypass time (P =
      .005), and diabetes (P = .003). At 3 months, patients had improvements in both
      physical and mental components of QOL, independent of the occurrence of POCDs (P
      > .5). Independent predictors of improved QOL included younger age, severe
      preoperative anginal symptoms, normal left ventricular function, absence of
      postoperative wound infection, but not POCDs. CONCLUSIONS: Neurocognitive
      deficits can be frequently detected on comprehensive neuropsychometric testing
      after cardiac surgery. However, they are not associated with any clinically
      important differences in patient outcome or in QOL after surgery.

PMID- 23535153
TI  - Hybrid repair of Kommerell diverticulum.
AB  - OBJECTIVE: Kommerell diverticulum carries the risk of rupture or dissection if
      left untreated. Various methods of repair have been described, and options have
      recently expanded to include the hybrid approach. This study describes hybrid
      repair techniques for Kommerell diverticulum and assesses outcomes. METHODS:
      Between 2005 and 2010, a total of 10 patients underwent hybrid repair of
      Kommerell diverticulum (3 right-sided arches) by elephant trunk with endovascular
      completion (n = 4), frozen elephant trunk (n = 3), or stent grafting with
      cervical debranching (n = 3). Mean age at procedure was 57 +/- 25.5 years.
      Subclavian artery revascularization was performed preoperatively (n = 4),
      intraoperatively (n = 3), or postoperatively (n = 3), either as carotid-to
      subclavian bypass (n = 7; n = 3 bilateral) or originating from the ascending
      aorta (n = 3). Data were obtained from the prospectively collected database and
      chart review. RESULTS: There was no in-hospital mortality, nor were there any
      cases of respiratory or renal failure. There were no cases of paraplegia, but
      there was 1 stroke. Two patients had type 2 endoleaks develop; 1 required
      subclavian coil embolization. Mean hospital stay was 8.73 +/- 4 days. After
      repair, there were no ruptures, no significant growth, and all patients remain
      free of symptoms. CONCLUSIONS: Hybrid repair is a safe and effective surgical
      treatment option for Kommerell diverticulum. Selection of the specific type of
      intervention is based on patient anatomy and comorbid conditions.

PMID- 23535154
TI  - Azelnidipine suppresses the progression of aortic aneurysm in wild mice model
      through anti-inflammatory effects.
AB  - BACKGROUND: Although systemic hypertension is closely associated with aortic
      aneurysm (AA) formation, there are many patients with AA without hypertension. In
      these patients, an inflammation-mediated progression of aneurysmal disease is
      likely responsible for AA growth and eventual rupture. Unfortunately, there
      remains no reproducible and durable small animal model of aortic aneurysmal
      disease, the development of which would enable the investigation of the
      pathophysiology of this vexing condition. The first aim was to establish a useful
      wild-type mouse model of AA with low mortality. The second aim was to use this
      model to assess the protective effect of azelnidipine, a new calcium channel
      blocker, against the progression of the AA independent of its antihypertensive
      effect. METHODS: Angiotensin II and beta-aminopropionitrile (a lysyl oxidase
      inhibitor) were administrated subcutaneously in 7-week-old C57BL/6J mice using an
      osmotic minipump for 4 weeks to generate a wild-type mouse model of AA.
      Concurrently, azelnidipine (a calcium channel blocker) or a placebo was
      administrated orally for 4 weeks. Mice were humanely killed and assessed at the
      end of the 4 weeks of pharmacologic manipulation. RESULTS: The combined infusion
      of angiotensin II and beta-aminopropionitrile induced degenerative aneurysm of
      the thoracic and/or abdominal aorta (11/12; 92%). The majority of aneurysms were
      located in the distal aortic arch and suprarenal abdominal aorta. Although there
      was no difference in systolic blood pressure between the control and azelnidipine
      treated groups, azelnidipine significantly reduced the incidence of AA (2/11;
      18%). Azelnidipine treatment reduced the pathologic findings normally associated
      with aneurysm formation within the aortic wall. Azelnidipine also reduced the
      number of macrophage antigen-3 (MAC-3)-positive cells in the periaortic adipose
      tissue and reduced the gene expression levels of tumor necrosis factor-alpha and
      matrix metalloproteinase-2 and -9 within the aortic wall. CONCLUSIONS: This study
      demonstrates that combined treatment with angiotensin II and beta
      aminopropionitrile induces degenerative AAs in wild-type mice, and azelnidipine
      prevents aneurysm progression via its anti-inflammatory effect.

PMID- 23535155
TI  - Day/night variability in blood pressure: influence of posture and physical
      activity.
AB  - BACKGROUND: Blood pressure (BP) is highest during the day and lowest at night.
      Absence of this rhythm is a predictor of cardiovascular morbidity and mortality.
      Contributions of changes in posture and physical activity to the 24-hour
      day/night rhythm in BP are not well understood. We hypothesized that postural
      changes and physical activity contribute substantially to the day/night rhythm in
      BP. METHODS: Fourteen healthy, sedentary, nonobese, normotensive men (aged 19-50
      years) each completed an ambulatory and a bed rest condition during which BP was
      measured every 30-60 minutes for 24 hours. When ambulatory, subjects followed
      their usual routines without restrictions to capture the "normal" condition.
      During bed rest, subjects were constantly confined to bed in a 6-degree head-down
      position; therefore posture was constant, and physical activity was minimized.
      Two subjects were excluded from analysis because of irregular sleep timing.
      RESULTS: The systolic and diastolic BP reduction during the sleep period was
      similar in ambulatory (-11+/-2mmHg/-8+/-1mmHg) and bed rest conditions (-8+/
      3mmHg/-4+/-2mmHg; P = 0.38/P = 0.12). The morning surge in diastolic BP was
      attenuated during bed rest (P = 0.001), and there was a statistical trend for the
      same effect in systolic BP (P = 0.06). CONCLUSIONS: A substantial proportion of
      the 24-hour BP rhythm remained during bed rest, indicating that typical daily
      changes in posture and/or physical activity do not entirely explain 24-hour BP
      variation under normal ambulatory conditions. However, the morning BP increase
      was attenuated during bed rest, suggesting that the adoption of an upright
      posture and/or physical activity in the morning contributes to the morning BP
      surge.

PMID- 23535156
TI  - Impairment of regulatory T cells in myasthenia gravis: studies in an experimental
      model.
AB  - Myasthenia gravis (MG) is an antibody mediated, T cell dependent autoimmune
      disease characterized by muscle fatigability in which autoantibodies directed to
      the acetylcholine receptor (AChR) impair neuromuscular transmission. The
      identification of CD4+CD25+Foxp3+Treg cells as important regulators of tolerance
      opened a major area of investigation raising the possibility that a dysfunction
      in the Treg compartment is involved in the etiology and pathogenesis of
      autoimmune diseases, including MG. In this paper we summarize shortly Treg
      abnormalities that were reported in MG patients and report on our studies of Treg
      in experimental autoimmune MG (EAMG). Hopefully these studies would pave the way
      towards the development of novel Treg-based treatment modalities that will
      restore self-tolerance in MG and other autoimmune diseases. In our previous
      studies in EAMG we have shown that Treg cells transferred from healthy rat donors
      to myasthenic rats suppress EAMG. However, Treg cells from sick animals do not
      have the same in vivo suppressive activity as those from healthy donors. The
      objective of the present study was to further characterize quantitative and
      qualitative alterations in Treg cells of rats with EAMG. We found that the
      frequency of CD4+CD25+Foxp3+Treg cells within the spleen and PBL was decreased in
      EAMG rats as compared to naive and CFA-immunized healthy controls. Treg cells
      from myasthenic rats were less effective than Treg cells from controls in
      suppressing the proliferation of CD4+T effector cells in response to ConA and of
      B cells in response to LPS. Moreover, CD4+CD25+ cells from EAMG rats exhibited an
      elevated extent of apoptosis and expressed upregulated levels of FAS and of Th17
      associated cytokines. Since EAMG is an induced disease, these quantitative and
      qualitative alterations in Treg cells do not reflect predisposing impairments and
      seem to be associated with the specific autoimmune response resulting from AChR
      immunization.

PMID- 23535157
TI  - Etiology of myasthenia gravis: innate immunity signature in pathological thymus.
AB  - Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular
      junction (NMJ), whose clinical hallmark is muscle weakness and early
      fatigability. The main target of autoimmunity in MG is the acetylcholine receptor
      (AChR) located in the NMJ. It is now widely accepted that the thymus is probably
      the prime site of autoimmunity development and maintenance in AChR-positive MG
      patients; however, the exact mechanisms triggering and perpetuating the intra
      thymic autoimmune response to AChR are still unknown. As with many autoimmune
      diseases, MG has a multifactorial etiology, resulting from complex interactions
      between genetic and environmental factors, as fully described in this review.
      Among environmental factors, viral infections could play a central role in
      autoimmunity, mainly through the induction of dysregulated Toll-like receptor
      (TLR)-mediated innate immune responses, which can lead to inflammation and
      adaptive autoimmune response. Growing evidence of chronic inflammation, TLR
      activation, and persistent viral infections in the thymus of MG patients,
      strongly supports the hypothesis that, in the context of a genetic susceptible
      background, the intrathymic innate immune responses to pathogen infections might
      contribute to MG etiology.

PMID- 23535158
TI  - Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific
      kinase.
AB  - Myasthenia gravis (MG) with antibodies to the muscle-specific receptor tyrosine
      kinase (MuSK-MG) is a rare disease which covers 5-8% of all MG patients. Symptoms
      are nearly always generalized, though more focal than in MG with anti
      acetylcholine receptor antibodies, with predominant involvement of cranial,
      bulbar and axial muscles; early respiratory crises are frequent. Focal atrophy,
      mostly of facial, masseter and tongue muscles, occurs in a proportion of
      patients. Diagnosis is often challenging on account of atypical presentation with
      little or no symptom fluctuations, lack of response to acetylcholinesterase
      inhibitors in a high proportion of patients and negative results of
      electrodiagnostic studies when performed on limb muscles. Immunosuppression is
      the mainstay of treatment, since the response to acetylcholinesterase inhibitors
      is generally unsatisfactory and thymectomy does not appear to improve the course
      of the disease. Although corticosteroids result in marked improvement, disease
      flares are frequent during prednisone dosage tapering and most patients remain
      dependent on treatment. Since treatment with rituximab, in uncontrolled studies,
      induced sustained benefit in patients with refractory disease, B cell depletion
      is an attractive option for MuSK-MG patients unresponsive to conventional
      immunosuppressants.

PMID- 23535159
TI  - The different roles of the thymus in the pathogenesis of the various myasthenia
      gravis subtypes.
AB  - The thymus plays distinct roles in the pathogenesis of the different Myasthenia
      gravis (MG) subtypes. Inflammatory, neoplastic and age-related alterations of the
      thymus are of pivotal relevance for the initiation of anti-acetylcholine receptor
      (AChR) autoimmunity in early onset MG, thymoma-associated MG and, likely, late
      onset MG, respectively. By contrast, the thymus is presumably not related to MG
      that is due to autoantibodies to the muscle specific kinase, MuSK. Finally, the
      role of the thymus is still obscure in MG defined by antibodies against the agrin
      receptor LRP4 and in MG without all of the above autoantibdies (triple sero
      negative MG) since these MG subtypes have been described only recently and
      thymectomy has not been their standard treatment. This review aims to give an
      update on intrathymic mechanisms of tolerance breakdown in MG, including abnormal
      T cell selection and activation, the role of thymic myoid cells, the autoimmune
      regulator (AIRE) and regulatory T cells.

PMID- 23535160
TI  - Pathophysiology of myasthenia gravis with antibodies to the acetylcholine
      receptor, muscle-specific kinase and low-density lipoprotein receptor-related
      protein 4.
AB  - Myasthenia gravis is caused by antibodies to the acetylcholine receptor, muscle
      specific kinase, low-density lipoprotein receptor-related protein 4, or possibly
      yet unidentified antibodies. The mechanisms by which these antibodies interfere
      with the function of postsynaptic proteins include complement activation,
      antigenic modulation by crosslinking of the target proteins, competition with
      ligand binding sites, or steric hindrance which inhibits conformational changes
      or binding to associated proteins. Screening for auto-antibodies to different
      postsynaptic targets, and also for low-affinity antibodies, is contributing to a
      more accurate diagnosis of MG patients. Further studies into the specific
      pathophysiological pathways of the several MG subforms might help to develop new,
      more antigen specific, therapies.

PMID- 23535161
TI  - Cutting edge in myasthenia gravis.

PMID- 23535162
TI  - Newly developed liver-retraction method for laparoscopic gastric surgery using a
      silicone disc: the phi-shaped technique.

PMID- 23535163
TI  - Blood transfusion for lower extremity bypass is associated with increased wound
      infection and graft thrombosis.
AB  - BACKGROUND: Packed RBC transfusion has been postulated to increase morbidity and
      mortality after cardiac/general surgical operations, but its effects after lower
      extremity bypass (LEB) have not been studied extensively. STUDY DESIGN: Using the
      Vascular Study Group of New England's database (2003-2010), we examined 1,880
      consecutive infrainguinal LEB performed for critical limb ischemia. Perioperative
      transfusion was categorized as 0 U, 1 to 2 U, and >=3 U. Cohort frequency group
      matching was used to compare groups of patients receiving 1 to 2 U and 0 U with
      patients receiving >=3 U using age, coronary artery disease, diabetes, urgency,
      and indication of revascularization. Primary end points were perioperative
      mortality, wound infection, and loss of primary graft patency at discharge, as
      well as 1-year mortality and loss of primary graft patency. RESULTS: In the study
      cohort, 1,532 LEBs (81.5%) received 0 U, 248 LEBs (13.2%) received 1 to 2 U, and
      100 LEBs (5.3%) received >=3 U transfusion. In the study cohort and group
      frequency matched cohort, transfusion was associated with significantly higher
      perioperative wound infection (0 U:4.8% vs 1 to 2 U: 6.5% vs >=3 U: 14.0%; p =
      0.0004) and graft thrombosis at discharge (4.5% vs 7.7% vs 15.3%; p < 0.0001). At
      1 year, there were no differences in infection or graft patency. In multivariate
      analysis, transfusion was independently associated with increased perioperative
      wound infection in the study cohort and group frequency matched cohort (1 to 2 U
      vs 0 U: adjusted odds ratio [OR] = 1.4; 95% CI, 0.8-2.5; p = 0.263; >=3 U vs 0 U:
      OR = 3.5; 95% CI, 1.8-6.7; p = 0.0002; overall p = 0.002) and increased graft
      thrombosis at discharge (1 to 2 U vs 0 U: OR = 2.1; 95% CI, 1.2-3.6; p = 0.01;
      >=3 U vs 0 U: OR = 4.8; 95% CI, 2.5-9.2; p < 0.0001, overall p < 0.0001).
      CONCLUSIONS: Perioperative transfusion in patients undergoing LEB is associated
      with increased perioperative wound infection and graft thrombosis. From this
      observational study, it appears transfusion does not have major consequences
      during mid-term follow-up, but the presumed benefits of blood replacement should
      be weighed carefully because of the increased risk of perioperative complications
      with transfusion.

PMID- 23535164
TI  - Inhibition of Succinate Dehydrogenase by Diazoxide Is Independent of the ATP
      Sensitive Potassium Channel Subunit Sulfonylurea Type 1 Receptor.
AB  - BACKGROUND: Diazoxide maintains myocyte volume and contractility during stress
      via an unknown mechanism. The mechanism of action may involve an undefined
      (genotype unknown) mitochondrial ATP-sensitive potassium channel and is dependent
      on the ATP-sensitive potassium channel subunit sulfonylurea type 1 receptor
      (SUR1). The ATP-sensitive potassium channel openers have been shown to inhibit
      succinate dehydrogenase (SDH) and a gene for a portion of SDH has been found in
      the SUR intron. Diazoxide may be cardioprotective via inhibition of SDH, which
      can form part of an ATP-sensitive potassium channel or share its genetic
      material. This study investigated the role of inhibition of SDH by diazoxide and
      its relationship to the SUR1 subunit. STUDY DESIGN: Mitochondria were isolated
      from wild-type and SUR1 knockout mice. Succinate dehydrogenase activity was
      measured by spectrophotometric analysis of 2,6-dichloroindophenol reduction for
      20 minutes as the relative change in absorbance over time. Mitochondria were
      treated with succinate (20 mM), succinate + 1% dimethylsulfoxide, succinate +
      malonate (8 mM) (competitive inhibitor of SDH), or succinate + diazoxide (100
      MUM). RESULTS: Both malonate and diazoxide inhibit SDH activity in mitochondria
      of wild-type mice and in mice lacking the SUR1 subunit (p < 0.05 vs control).
      CONCLUSIONS: The ability of DZX to inhibit SDH persists even after deletion of
      the SUR1 gene. Therefore, the enzyme complex SDH is not dependent on the SUR1
      gene. The inhibition of SDH by DZX can play a role in the cardioprotection
      afforded by DZX; however, this role is independent of the ATP-sensitive potassium
      channel subunit SUR1.

PMID- 23535165
TI  - Rationale and design of the SERVE-HF study: treatment of sleep-disordered
      breathing with predominant central sleep apnoea with adaptive servo-ventilation
      in patients with chronic heart failure.
AB  - AIMS: Central sleep apnoea/Cheyne-Stokes respiration (CSA/CSR) is a risk factor
      for increased mortality and morbidity in heart failure (HF). Adaptive servo
      ventilation (ASV) is a non-invasive ventilation modality for the treatment of
      CSA/CSR in patients with HF. METHODS: SERVE-HF is a multinational, multicentre,
      randomized, parallel trial designed to assess the effects of addition of ASV
      (PaceWave, AutoSet CS; ResMed) to optimal medical management compared with
      medical management alone (control group) in patients with symptomatic chronic HF,
      LVEF <=45%, and predominant CSA. The trial is based on an event-driven group
      sequential design, and the final analysis will be performed when 651 events have
      been observed or the study is terminated at one of the two interim analyses. The
      aim is to randomize ~1200 patients to be followed for a minimum of 2 years.
      Patients are to stay in the trial up to study termination. The first patient was
      randomized in February 2008 and the study is expected to end mid 2015. The
      primary combined endpoint is the time to first event of all-cause death,
      unplanned hospitalization (or unplanned prolongation of a planned
      hospitalization) for worsening (chronic) HF, cardiac transplantation,
      resuscitation of sudden cardiac arrest, or appropriate life-saving shock for
      ventricular fibrillation or fast ventricular tachycardia in implantable
      cardioverter defibrillator patients. PERSPECTIVES: The SERVE-HF study is a
      randomized study that will provide important data on the effect of treatment with
      ASV on morbidity and mortality, as well as the cost-effectiveness of this
      therapy, in patients with chronic HF and predominantly CSA/CSR. TRIAL
      REGISTRATION: ISRCTN19572887.

PMID- 23535167
TI  - Methionine salvage and S-adenosylmethionine: essential links between sulfur,
      ethylene and polyamine biosynthesis.
AB  - Both Met (methionine) and SAM (S-adenosylmethionine), the activated form of Met,
      participate in a number of essential metabolic pathways in plants. The
      subcellular compartmentalization of Met fluxes will be discussed in the present
      review with respect to regulation and communication with the sulfur assimilation
      pathway, the network of the aspartate-derived amino acids and the demand for
      production of SAM. SAM enters the ethylene, nicotianamine and polyamine
      biosynthetic pathways and provides the methyl group for the majority of
      methylation reactions required for plant growth and development. The multiple
      essential roles of SAM require regulation of its synthesis, recycling and
      distribution to sustain these different pathways. A particular focus of the
      present review will be on the function of recently identified genes of the Met
      salvage cycle or Yang cycle and the importance of the Met salvage cycle in the
      metabolism of MTA (5'-methylthioadenosine). MTA has the potential for product
      inhibition of ethylene, nicotianamine and polyamine biosynthesis which provides
      an additional link between these pathways. Interestingly, regulation of Met cycle
      genes was found to differ between plant species as shown for Arabidopsis thaliana
      and Oryza sativa.

PMID- 23535166
TI  - The cell cycle and pluripotency.
AB  - PSCs (pluripotent stem cells) possess two key properties that have made them the
      focus of global research efforts in regenerative medicine: they have unlimited
      expansion potential under conditions which favour their preservation as PSCs and
      they have the ability to generate all somatic cell types upon differentiation
      (pluripotency). Conditions have been defined in vitro in which pluripotency is
      maintained, or else differentiation is favoured and is directed towards specific
      somatic cell types. However, an unanswered question is whether or not the core
      cell cycle machinery directly regulates the pluripotency and differentiation
      properties of PSCs. If so, then manipulation of the cell cycle may represent an
      additional tool by which in vitro maintenance or differentiation of PSCs may be
      controlled in regenerative medicine. The present review aims to summarize our
      current understanding of links between the core cell cycle machinery and the
      maintenance of pluripotency in ESCs (embryonic stem cells) and iPSCs (induced
      PSCs).

PMID- 23535171
TI  - With an antibody whose duty's double, a step towards ending asthma trouble?
AB  - Asthma is a debilitating chronic inflammatory disease of the airways that results
      in shortness of breath, wheezing and coughing, often triggered by inhalation of
      common allergens. The prevalence and severity of asthma has increased
      dramatically over the last several decades to the point where several hundred
      million people worldwide are affected and each year tens of thousands of
      individuals die prematurely from asthma symptoms. The rise in disease prevalence
      is particularly evident in the developed world, where childhood exposure to
      bacteria and viruses has decreased dramatically, while the use of antibiotics,
      especially early in life, and births by Caesarean section have increased
      significantly; correlations that support the hygiene hypothesis. Central to the
      pathogenesis of asthma are the roles of TH2-type cytokines, including IL
      (interleukin)-4, IL-5, IL-9 and IL-13, in stimulating and perpetuating an
      inflammatory cascade that drives detrimental changes in airway structure and
      function. IL-4 and IL-13, in particular, have been targets of therapeutic
      development because, together, they specifically promote nearly all of the
      clinical features of asthma. Their inflammatory functions are highly
      complementary, but not identical, in large part because they share cell-surface
      receptors and transcription factors through which they stimulate cell signalling.
      In this issue of the Biochemical Journal, Redpath et al. have taken advantage of
      the shared receptor nature of the IL-4- and IL-13-mediated inflammatory responses
      to generate a novel antibody to the third ectodomain (D3) of IL-13Ralpha1 (IL-13
      receptor alpha1), which forms a requisite binding site for both interleukins.
      This antibody potently neutralizes both IL-4 and IL-13 activities in vitro. Using
      X-ray crystallography complemented by molecular interaction and functional
      analyses, they clearly define its mechanism of dual cytokine neutralization as
      one of molecular mimicry of the interleukin-receptor interaction. Considering the
      complexity of the cytokine-mediated inflammatory cascade that defines asthma
      pathogenesis, such therapeutics that can effectively and simultaneously
      neutralize the actions of multiple cytokines and may play a significantly
      expanded role in the treatment and prevention of asthma in the future.

PMID- 23535172
TI  - Feasibility of using ultrasound to measure preterm body composition and to assess
      macronutrient influences on tissue accretion rates.
AB  - BACKGROUND AND AIMS: To assess ultrasound as a method for (i) measuring body
      composition (BC) of preterm infants and for (ii) assessing the influence of
      macronutrient intakes on tissue accretion rates. METHODS: Preterm ultrasound
      studies of four anatomical sites were performed approximately every three weeks
      from birth to corrected-term age. Preterm measurements were compared to foetal
      reference data. Duplicate scans at each site were taken on a subset of infants to
      test the reproducibility of the method, assessed as the coefficient of variation
      (CV). The influence of measured macronutrient intakes on preterm BC was assessed
      by regression analysis. RESULTS: Median (range) gestation and birth weight of 40
      preterm infants were 27 (23-29) weeks and 1022 (480-1475) g, respectively.
      Accretion rates of adipose and muscle tissues were not uniform across the four
      sites. Relative to the foetus, preterm adipose tissue thickness was reduced at an
      equivalent (corrected) gestation, but towards term, a faster accretion rate of
      subcutaneous abdominal adipose and limb muscle tissue was evident. Timing of
      fortification (p=0.012), enteral carbohydrate intake (p=0.008) and the protein
      energy ratio of intakes (p=0.038) moderated the ratio of adipose to muscle tissue
      accretion over the four sites by -0.004, -0.048 and -0.042, respectively.
      CONCLUSIONS: Ultrasound provides a non-invasive, portable method of assessing
      changes in subcutaneous adipose tissue and muscle accretion and appears
      sufficiently sensitive to detect influences of macronutrient intakes on accretion
      rates from birth. The method warrants further investigation as a bedside tool for
      measuring BC of preterm infants.

PMID- 23535173
TI  - The Continuing Challenge of Reducing HIV Risk among Haitian Youth: The Need for
      Intervention.
AB  - There is a dire need for interventions that will address the multiple factors-
      poverty, substance use, early sexual debut, and violence--that influence Haitian
      youth's engagement in risky behaviors. The deteriorating socioeconomic and
      political state of the country has had a deleterious effect on the sociocultural
      milieu and on the boundaries that have heretofore kept risky behaviors in check.
      Historically, the lakou system, a community-based approach that supports the
      family unit, has disintegrated, leading to the disruption of traditional
      parenting patterns. The unstable economic system has also led to the increasing
      use of children from poor families, who through the restavek system, are sent to
      work as servants in other households. The breakdown of traditional systems,
      coupled with the increasing economic and political instability, has had a
      significant effect on Haitian adolescents. Among boys, increased levels of
      substance use have been associated with multiple sex partnerships and very early
      sexual debut. Among girls, extremely high rates of sexual abuse and forced sex
      have led to relatively high levels of HIV. While the majority of them have been
      exposed to behavior change messages, behavior change itself has lagged because
      many adolescents do not accurately perceive their risk exposure. This review
      explores the risks of HIV transmission among Haitian youth, with a focus on
      vulnerability factors, including substance use, culture, and the socioeconomic
      context, and provides recommendations for intervention. An ecosystemic approach,
      designed specifically for Haitian youth and that takes environmental context and
      culture into account, is needed.

PMID- 23535174
TI  - Dietary calcium from dairy and nondairy sources, and risk of symptomatic kidney
      stones.
AB  - PURPOSE: Because of high correlations between dairy intake and total dietary
      calcium, previously reported associations between lower calcium intake and
      increased kidney stone risk represent de facto associations between milk products
      and risk. We examined associations between dietary calcium from nondairy and
      dairy sources, and symptomatic nephrolithiasis. MATERIALS AND METHODS: We
      performed prospective studies in the Health Professionals Follow-up Study (HPFS)
      in 30,762 men, and in the Nurses' Health Study (NHS) I and II in 94,164 and
      101,701 women, respectively. We excluded men 60 years old or older because we
      previously reported inverse associations between calcium intake and risk only in
      men younger than 60 years. Food frequency questionnaires were used to assess
      calcium intake every 4 years. We used Cox proportional hazards regression to
      adjust for age, body mass index, supplemental calcium, diet and other factors.
      RESULTS: We documented 5,270 incident kidney stones during the combined 56 years
      of followup. In participants in the highest vs the lowest quintile of nondairy
      dietary calcium the multivariate relative risk of kidney stones was 0.71 (95% CI
      0.56-0.92, p for trend 0.007) in HPFS, 0.82 (95% CI 0.69-0.98, p trend 0.08) in
      NHS I and 0.74 (95% CI 0.63-0.87, p trend 0.002) in NHS II. When comparing the
      highest to the lowest quintile of dairy calcium, the multivariate relative risk
      was 0.77 (95% CI 0.63-0.95, p trend 0.01) for HPFS, 0.83 (95% CI 0.69-0.99, p
      trend 0.05) for NHS I and 0.76 (95% CI 0.65-0.88, p trend 0.001) for NHS II.
      CONCLUSIONS: Higher dietary calcium from nondairy or dairy sources is
      independently associated with a lower kidney stone risk.

PMID- 23535175
TI  - Role of Rck-Pat1b binding in assembly of processing-bodies.
AB  - The DEAD box RNA helicase Rck and the scaffold protein Pat1b participate in
      controlling gene expression at the post-transcriptional level by suppressing mRNA
      translation and promoting mRNA decapping. In addition, both proteins are required
      for the assembly of processing (P)-bodies, cytoplasmic foci that contain stalled
      mRNAs and numerous components of the mRNA decay machinery. The C-terminal RecA
      like domain of Rck interacts with the N-terminal acidic domain of Pat1b. Here, we
      identified point mutations in human Rck and Pat1b that prevent the two proteins
      from binding to each other. By analyzing interaction-deficient mutants in
      combination with knockdown and rescue strategies in human HeLa cells, we found
      that Pat1b assembles P-bodies and suppresses expression of tethered mRNAs in the
      absence of Rck binding. In contrast, Rck requires the Pat1b-binding site in order
      to promote P-body assembly and associate with the decapping enzyme Dcp2 as well
      as Ago2 and TNRC6A, two core components of the RNA-induced silencing complex. Our
      data indicate that P-body assembly occurs in a step-wise manner, where Rck
      participates in the initial suppression of mRNA translation, whereas Pat1b in a
      second step triggers P-body assembly and promotes mRNA decapping.

PMID- 23535176
TI  - Epitaxial cobalt oxide films on Ir(100)-the importance of crystallographic
      analyses.
AB  - Epitaxial cobalt oxide films on Ir(100) exhibit a rich scenario of different
      structural phases which are reviewed in this paper. The great majority of phases
      could be, as a rare case, crystallographically described by the joint application
      of atomically resolved STM and quantitative LEED, whereby structural surprises
      were more the rule than the exception. So, the oxide grows in the polar (111)
      orientation for both the Co3O4 and CoO stoichiometry on the bare Ir substrate in
      spite of the latter's square symmetry. Moreover, the film orientation can be
      tuned to non-polar (100) growth when one or several pseudomorphic Co layers are
      introduced as an interface between oxide and Ir substrate. By using the
      nanostructured Ir(100)-(5 * 1)-H phase as a template a nanostructured Co film can
      be formed whose oxidation leads to a nanostructured oxide. The nominally polar
      films circumvent the polarity problem by appropriate surface terminations. That
      of CoO(111) is, again as a surprise, realized by a switch from rocksalt-type to
      wurtzite-type stacking near the surface, by which the latter becomes metallic.
      The stepwise oxidation of a pseudomorphic Co layer on the bare Ir substrate leads
      to the sequential formation of rocksalt-type tetrahedral Co-O building blocks
      (with intermediate BN-type blocks) whereby the Co species more and more assume
      positions determined by the inner-oxidic binding.

PMID- 23535177
TI  - Cerebellar sensory processing alterations impact motor cortical plasticity in
      Parkinson's disease: clues from dyskinetic patients.
AB  - The plasticity of primary motor cortex (M1) in patients with Parkinson's disease
      (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently
      reported in young healthy subjects that inhibitory cerebellar stimulation
      enhanced the sensorimotor plasticity of M1 that was induced by paired associative
      stimulation (PAS). This study demonstrates that the deficient sensorimotor M1
      plasticity in 16 patients with LIDs could be reinstated by a single session of
      real inhibitory cerebellar stimulation but not sham stimulation. This was evident
      only when a sensory component was involved in the induction of plasticity,
      indicating that cerebellar sensory processing function is involved in the
      resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on
      LIDs is known. To explore whether this benefit is linked to the restoration of
      sensorimotor plasticity of M1, we conducted an additional study looking at
      changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral,
      real inhibitory cerebellar stimulation or sham stimulation. Only real and not
      sham stimulation had an antidyskinetic effect and it was paralleled by a
      resurgence in the sensorimotor plasticity of M1. These results suggest that
      alterations in cerebellar sensory processing function, occurring secondary to
      abnormal basal ganglia signals reaching it, may be an important element
      contributing to the maladaptive sensorimotor plasticity of M1 and the emergence
      of abnormal involuntary movements.

PMID- 23535178
TI  - Structural covariance networks of the dorsal anterior insula predict females'
      individual differences in empathic responding.
AB  - Previous functional imaging studies have shown key roles of the dorsal anterior
      insula (dAI) and anterior midcingulate cortex (aMCC) in empathy for the suffering
      of others. The current study mapped structural covariance networks of these
      regions and assessed the relationship between networks and individual differences
      in empathic responding in 94 females. Individual differences in empathy were
      assessed through average state measures in response to a video task showing
      others' suffering, and through questionnaire-based trait measures of empathic
      concern. Overall, covariance patterns indicated that dAI and aMCC are principal
      hubs within prefrontal, temporolimbic, and midline structural covariance
      networks. Importantly, participants with high empathy state ratings showed
      increased covariance of dAI, but not aMCC, to prefrontal and limbic brain
      regions. This relationship was specific for empathy and could not be explained by
      individual differences in negative affect ratings. Regarding questionnaire-based
      empathic trait measures, we observed a similar, albeit weaker modulation of dAI
      covariance, confirming the robustness of our findings. Our analysis, thus,
      provides novel evidence for a specific contribution of frontolimbic structural
      covariance networks to individual differences in social emotions beyond negative
      affect.

PMID- 23535179
TI  - Effects of number magnitude and notation at 7T: separating the neural response to
      small and large, symbolic and nonsymbolic number.
AB  - We examined the effects of number magnitude (within vs. outside the subitizable
      range) and notation (symbolic vs. nonsymbolic number) on neural responses to
      visual displays in the human brain using fMRI at 7T. We found that the right
      temporoparietal junction (rTPJ) responded more strongly to small than to larger
      numbers (2, 4 > 6, 8), while there was greater activity bilaterally within and
      around the intraparietal sulcus (IPS) as number magnitude increased (6, 8 > 2,
      4). The effects of number magnitude were greatest for nonsymbolic stimuli. In
      addition, there was striking overlap between rTPJ regions responding to small
      numbers and those most strongly activated by symbolic stimuli, and between IPS
      regions responding to large numbers and those most activated by nonsymbolic
      stimuli. The results are consistent with distinct neural processes recruited for
      the processing of small- and large-number magnitudes. Contributions due to
      differences in representing exact number (small nonsymbolic arrays and all
      symbolic numbers, in rTPJ) and overall magnitude (particularly with large
      nonsymbolic arrays, in IPS), and the associated theoretical implications of the
      findings, are discussed.

PMID- 23535180
TI  - Distinct neural markers of TVA-based visual processing speed and short-term
      storage capacity parameters.
AB  - An individual's visual attentional capacity is characterized by 2 central
      processing resources, visual perceptual processing speed and visual short-term
      memory (vSTM) storage capacity. Based on Bundesen's theory of visual attention
      (TVA), independent estimates of these parameters can be obtained from
      mathematical modeling of performance in a whole report task. The framework's
      neural interpretation (NTVA) further suggests distinct brain mechanisms
      underlying these 2 functions. Using an interindividual difference approach, the
      present study was designed to establish the respective ERP correlates of both
      parameters. Participants with higher compared to participants with lower
      processing speed were found to show significantly reduced visual N1 responses,
      indicative of higher efficiency in early visual processing. By contrast, for
      participants with higher relative to lower vSTM storage capacity, contralateral
      delay activity over visual areas was enhanced while overall nonlateralized delay
      activity was reduced, indicating that holding (the maximum number of) items in
      vSTM relies on topographically specific sustained activation within the visual
      system. Taken together, our findings show that the 2 main aspects of visual
      attentional capacity are reflected in separable neurophysiological markers,
      validating a central assumption of NTVA.

PMID- 23535181
TI  - Retinal artery-vein caliber grading using color fundus imaging.
AB  - Recent research suggests that retinal vessel caliber (or cross-sectional width)
      measured from retinal photographs is an important feature for predicting
      cardiovascular diseases (CVDs). One of the most utilized measures is to quantify
      retinal arteriolar and venular caliber as the Central Retinal Artery Equivalent
      (CRAE) and Central Retinal Vein Equivalent (CRVE). However, current computer
      tools utilize manual or semi-automatic grading methods to estimate CRAE and CRVE.
      These methods involve a significant amount of grader's time and can add a
      significant level of inaccuracy due to repetitive nature of grading and
      intragrader distances. An automatic and time efficient grading of the vessel
      caliber with highly repeatable measurement is essential, but is technically
      challenging due to a substantial variation of the retinal blood vessels'
      properties. In this paper, we propose a new technique to measure the retinal
      vessel caliber, which is an "edge-based" vessel tracking method. We measured CRAE
      and CRVE from each of the vessel types. We achieve very high accuracy (average
      96.23%) for each of the cross-sectional width measurement compared to manually
      graded width. For overall vessel caliber measurement accuracy of CRAE and CRVE,
      we compared the results with an existing semi-automatic method which showed high
      correlation of 0.85 and 0.92, respectively. The intra-grader reproducibility of
      our method was high, with the correlation coefficient of 0.881 for CRAE and 0.875
      for CRVE.

PMID- 23535182
TI  - Value of cardiac CT in comprehensive aortic valve and root evaluation before
      percutaneous aortic valve replacement.
AB  - BACKGROUND: Aortic stenosis (AS) is the most frequent valvular heart disease, and
      patients who develop AS are at a high risk of sudden death. There is no medical
      cure available, and aortic valve replacement is the only effective treatment for
      advanced disease. Preoperative evaluation is the cornerstone of therapy and is
      necessary for selecting the implantation technique and valve. PURPOSE: To
      evaluate the role of cardiac CT in comprehensive aortic valve and aortic root
      evaluation before percutaneous aortic valve replacement. MATERIAL AND METHODS:
      Thirty-four patients with severe aortic valve stenosis were evaluated by cardiac
      CT. The aortic valve calcification grade defined by cardiac CT was compared to
      the operative findings. The mean calculated aortic annulus diameter (CAAD)
      measured by cardiac CT was compared to the aortic annulus diameter measured by
      transthoracic echocardiography (TTE) as well as during the operation. The
      distances from the aortic valve annulus to the coronary ostia (right and left)
      were measured by cardiac CT and compared to the intraoperative measurements. The
      findings from the CT coronary angiography and conventional coronary angiography
      were compared. RESULTS: There was strong agreement (k = 0.865) between the
      calcification grade by cardiac CT and the intraoperative grading. There was a
      stronger correlation (r = 0.948) between the CAAD assessed by cardiac CT and
      intraoperatively compared to the correlation between the intraoperative versus
      TTE measurements (r = 0.660). The distances measured between the aortic annulus
      and the right and left coronary artery ostia by cardiac CT were strongly
      correlated with the distances measured intraoperatively (r = 0.966 and 0.940 in
      the right and left sides, respectively). Cardiac CT detected three coronary
      artery stenotic lesions and three patent stents. All findings were confirmed by
      conventional coronary angiography. Thirteen percent of the evaluated coronary
      artery segments were of non-diagnostic quality by cardiac CT. CONCLUSION: Cardiac
      CT substantially facilitates the assessment of aortic root morphology prior to
      aortic valve replacement.

PMID- 23535183
TI  - Gastroduodenal artery recanalization after transcatheter fibered coil
      embolization for prevention of hepaticoenteric flow: incidence and predisposing
      technical factors in 142 patients.
AB  - BACKGROUND: Prophylactic occlusion of extrahepatic vessels prior to
      radioembolization or chemotherapy infusion is an effective method to prevent
      gastrointestinal complications. Unfortunately, vascular recanalization can occur.
      PURPOSE: To retrospectively determine the rate and technical factors associated
      with gastroduodenal artery (GDA) recanalization after transcatheter occlusion
      with fibered coils. MATERIAL AND METHODS: Patients with hepatic malignancy who
      underwent fibered coil occlusion of the GDA origin for radioembolization or
      hepatic arterial chemotherapy infusion with at least one subsequent hepatic
      angiogram between March 2006 and January 2011 were included. One hundred and
      forty-two patients (men, 71; women, 71) met study criteria. Hepatic arteriograms
      were reviewed to determine the frequency of arterial recanalization. Additional
      parameters included: patients' demographics, GDA diameter, length of coil pack,
      distance between GDA origin and most cephalad coil, persistent flow at the
      conclusion of the initial GDA occlusion procedure, platelet count, and
      international normalized ratio (INR). Chi-square test and pooled t-test were used
      to compare the two groups. Prospective multivariate analysis was performed with a
      logistic regression model. RESULTS: Twenty-nine of 142 patients (20.4%)
      experienced GDA recanalization. The distance between the GDA origin and most
      cephalad coil was significantly greater in the recanalization group than in the
      non-recanalization group (9.6 mm vs. 12.6 mm, P = 0.01). A prospective
      multivariate analysis established that the further the coil was from the origin
      the more likely the GDA was to recanalize. The two groups did not differ on the
      basis of any other factors examined. CONCLUSION: GDA origin recanalization after
      fibered coil occlusion is common. The distance between the GDA origin and most
      cephalad coil appears to be a predisposing factor for recanalization. Familiarity
      with this phenomenon is beneficial to reduce the likelihood of gastrointestinal
      tract complications during hepatic locoregional therapy.

PMID- 23535184
TI  - Good scent in MRI: can scent management optimize patient tolerance?
AB  - BACKGROUND: Psychological distress for patients undergoing magnetic resonance
      imaging (MRI) may range from mild anxiety to serious panic attacks. Scents
      associated with a sense of wellbeing have been used to diminish psychological
      stress in various clinical conditions. PURPOSE: To evaluate the influence of
      inhalation aromatherapy in the reduction of artifacts in patients undergoing MRI.
      MATERIAL AND METHODS: Based on the assumption aromatherapy will lead to
      significant reduction of patient-related motion artifacts (PRMA) in MRI, a
      randomized controlled trial with two groups of 54 patients was enrolled. The
      primary endpoint was the number of sequences with PRMAs. Secondary outcomes were
      improvements of mood measured with the ASTS questionnaire as well as patient's
      recommendation to fellow patients tested by a visual analogue scale. Incidence
      and intensity of adverse events were documented. RESULTS: Ninety-five patients
      were included in the statistical analysis. We were not able to detect a
      significant reduction of PRMAs. There were also no significant differences in
      mood or in relation to the feeling before and after examination. The only
      differences that neared significance were "positive mood" and "recommendation".
      No adverse reaction was observed. CONCLUSION: Although aromatherapy has been
      effective in enhancing patient's mood or wellbeing in a variety of stressful
      clinical settings, we were not able to find a similar effect. Neither the primary
      nor the secondary endpoints reached a clinical meaningful magnitude.

PMID- 23535185
TI  - Galangin attenuates mast cell-mediated allergic inflammation.
AB  - A great number of people are suffering from allergic inflammatory disease such as
      asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the
      treatment of these diseases is an important subject in human health. In this
      study, we investigated anti-allergic inflammatory effect of galangin and
      underlying mechanisms of action using in vitro and in vivo models. Galangin
      inhibited histamine release by the reduction of intracellular calcium in phorbol
      12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells
      (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, and IL-8. The
      inhibitory effect of galangin on theses pro-inflammatory cytokines was related
      with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear
      factor-kappaB, and caspase-1. Furthermore, galangin attenuated IgE-mediated
      passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the
      inflamed tissue. The inhibitory effects of galangin were more potent than
      cromolyn, a known anti-allergic drug. Our results showed that galangin down
      regulates mast cell-derived allergic inflammatory reactions by blocking histamine
      release and expression of pro-inflammatory cytokines. In light of in vitro and in
      vivo anti-allergic inflammatory effects, galangin could be a beneficial anti
      allergic inflammatory agent.

PMID- 23535186
TI  - Scoparone attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic
      failure through inhibition of toll-like receptor 4 signaling in mice.
AB  - The purpose of this study was to investigate the protective effects and molecular
      mechanisms of scoparone on d-galactosamine (D-GalN)/lipopolysaccharide (LPS)
      induced fulminant hepatic failure (FHF) in mice. FHF was induced in mice by
      intraperitoneal injection of D-GalN (800 mg/kg)/LPS (40 MUg/kg). Mice were
      treated intraperitoneally with scoparone 1h before D-GalN/LPS treatment.
      Treatment with d-GalN/LPS markedly increased mortality, serum aminotransferase
      activity, and tolllike receptor 4 (TLR4) protein expression, and these increases
      were attenuated by scoparone. Treatment with d-GalN/LPS markedly increased
      myeloid differentiation primary response gene 88 protein expression,
      phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N
      terminal kinase, nuclear protein expression of nuclear factor kappaB and
      phosphorylated c-Jun, and levels of serum tumor necrosis factor-alpha and
      interleukin-6 and these increases were attenuated by scoparone. In addition,
      increased levels of toll-receptor-associated activator of interferon protein
      expression, phosphorylation of interferon (IFN) regulatory factor 3, and serum
      IFN-beta level in D-GalN/LPS-treated mice were attenuated by scoparone. Our
      results suggest that scoparone attenuates d-GalN/LPSinduced liver damage by
      inhibition of the TLR-mediated inflammatory pathway.

PMID- 23535187
TI  - Distribution of the cardiotoxin pavettamine in the coffee family (Rubiaceae) and
      its significance for gousiekte, a fatal poisoning of ruminants.
AB  - Gousiekte, a cardiac syndrome of ruminants in southern Africa, is caused by the
      ingestion of plants containing the polyamine pavettamine. All the six known
      gousiekte-causing plants are members of the Rubiaceae or coffee family and house
      endosymbiotic Burkholderia bacteria in their leaves. It was therefore
      hypothesized that these bacteria could be involved in the production of the
      toxin. The pavettamine level in the leaves of 82 taxa from 14 genera was
      determined. Included in the analyses were various nodulated and non-nodulated
      members of the Rubiaceae. This led to the discovery of other pavettamine
      producing Rubiaceae, namely Psychotria kirkii and Psychotria viridiflora. Our
      analysis showed that many plant species containing bacterial nodules in their
      leaves do not produce pavettamine. It is consequently unlikely that the
      endosymbiont alone can be accredited for the synthesis of the toxin. Until now
      the inconsistent toxicity of the gousiekte-causing plants have hindered studies
      that aimed at a better understanding of the disease. In vitro dedifferentiated
      plant cell cultures are a useful tool for the study of molecular processes. Plant
      callus cultures were obtained from pavettamine-positive species. Mass
      spectrometric analysis shows that these calli do not produce pavettamine but can
      produce common plant polyamines. 

PMID- 23535188
TI  - Mechanisms of the anti-proliferative and anti-inflammatory effects of the herbal
      fixed combination STW 5 (Iberogast(r)) on colon adenocarcinoma (HT29) cells in
      vitro.
AB  - INTRODUCTION: Several conventional pharmaceuticals like non-steroidal anti
      inflammatory drugs (NSAIDS) or selective cyclooxygenase-2 (COX-2) inhibitors have
      been demonstrated to exert anti-proliferative effects and to induce apoptosis in
      a variety of cell lines, e.g. colon, stomach, or prostate cancer cells. STW 5
      (Iberogast((r))), a combination of nine plant extracts, is widely used in the
      treatment of gastrointestinal disorders, including functional dyspepsia and
      irritable bowel syndrome for which the involvement of an inflammatory etiology is
      discussed. To investigate the possible anti-proliferative effects, STW 5 and its
      components have been tested by using the colon-carcinoma cell line HT-29. The
      analyses have been performed in comparison to acetylsalicylic acid (ASA) and
      diclofenac (Diclo), which are well-known to reduce colon carcinoma risk. RESULTS:
      STW 5 showed significant anti-proliferative and pro-apoptotic effects on HT-29
      cancer cells, similar to NSAIDs under test. However, using the LDH assay, STW 5
      revealed significantly lower cytotoxicity than Diclo at same concentrations. In
      contrast to NSAIDs, STW 5 induced COX-1/COX-2, caspase-3 and Bax mRNA expressions
      in HT-29 and blocked LPS mediated translocation of the NF-kappaB p65 from the
      cytoplasm into the nucleus in PMA-differentiated THP-1 macrophages. These effects
      might be relevant, e.g. for prevention of undesirable side effects like gastric
      erosions. CONCLUSION: Our data suggest that the pro-apoptotic effect of STW 5 on
      HT-29 cells is involving multiple targets and is possibly due to an activation of
      the caspase cascade via mitochondrial destabilization. Active concentrations of
      STW 5 are, in relation to therapeutic doses, comparable to those of ASA and
      Diclo, suggesting a similar favorable effect on colon carcinoma risk.

PMID- 23535189
TI  - Paeoniflorin of Paeonia lactiflora prevents renal interstitial fibrosis induced
      by unilateral ureteral obstruction in mice.
AB  - Paeoniflorin (PF), the major active constituent of Paeonia lactiflora Pallas, has
      previously been reported to alleviate hepatic fibrosis. Whether and how it
      affects renal fibrosis was evaluated in the present study. The experimental renal
      fibrosis was induced by unilateral ureteral obstruction (UUO) operation in mice,
      and PF was orally administered for consecutive 7 days. Renal interstitial
      destruction and fibrosis degree were evaluated by histopathological examination
      and hydroxyproline assay. It was shown that PF treatment markedly ameliorated
      renal interstitial fibrotic lesions, attenuated synthesis of collagen and
      plasminogen activator inhibitor-1 (PAI-1), an important inhibitor of
      extracellular matrix degrading enzymes, in UUO mice. PF also suppressed
      epithelial-mesenchymal transition (EMT) by down-regulating TGF-beta1 expression
      and maintaining BMP-7 mRNA expression, and inhibited Smad2/3 activation in
      fibrotic kidneys induced by UUO. These observations suggest that PF can
      effectively prevent renal interstitial fibrosis, and the underlying mechanisms
      are, at least in part, through blocking EMT via BMP-7 recovery and TGF-beta/Smad
      signaling inhibition.

PMID- 23535190
TI  - The effects of storm-drains with periodic flows on intertidal algal assemblages
      in 'Ewa Beach (O'ahu), Hawai'i.
AB  - Storm-water drainage systems have potential to collect and focus nutrient
      enriched runoff into coastal systems. Storm-drain effluent could support
      macroalgal production and result in altered communities. To test this hypothesis,
      we assessed species composition and percent cover of native and non-native
      benthic macroalgae at eight intertidal sites along 'Ewa Beach, Hawai'i. Three
      sites contain storm-drainage outlets (drain 16-52 acres) that deliver effluent
      into the intertidal zone whereas five sites were located >= 100 m away and served
      as comparisons to determine differences related to the presence of storm-water.
      Results revealed lush and diverse macroalgal assemblages, similar at all sites.
      Furthermore, the abundance of non-native species (Acanthophora spicifera, Hypnea
      musciformis) was not related to presence of storm-drains. The finding that
      macroalgal assemblages are not related to storm-waters is contrary to an earlier
      investigation in the same location and underscores the importance of sampling
      design and habitat variation when assessing impacts.

PMID- 23535191
TI  - Assessing splenomegaly: automated volumetric analysis of the spleen.
AB  - RATIONALE AND OBJECTIVES: To define systematic volumetric thresholds to identify
      and grade splenomegaly and retrospectively evaluate the performance of
      radiologists to assess splenomegaly in computed tomography (CT) image data.
      MATERIALS AND METHODS: A clinical tool was developed to segment spleens from 172
      contrast-enhanced clinical CT studies. There were 45 normal and 127 splenomegaly
      cases confirmed by radiological reports. Spleen volumes were compared to manual
      measurements using overlap/error. Volumetric thresholds for mild/massive
      splenomegaly were defined at 1/2.5 standard deviations above the average splenic
      volume of the healthy population. The thresholds were validated against consensus
      reports. The performance of radiologists in assessing splenomegaly was
      retrospectively evaluated. RESULTS: The automated segmentation of spleens was
      robust with volume overlap/error of 95.2/3.3%. There were no significant
      differences (P > .2) between manual and automated segmentations for either
      normal/splenomegaly subgroups. Comparable correlations between interobserver and
      manual-automated measurements were found (r = 0.99 for all). The average volume
      of normal spleens was 236.89 +/- 77.58 mL. For splenomegaly, average volume was
      1004.75 +/- 644.27 mL. Volumetric thresholds of 314.47/430.84 mL were used to
      define mild/massive splenomegaly (+/-18.86 mL, 95% CI). Radiologists disagreed in
      23.25% (n = 40) of the diagnosed cases. The area under the receiver operating
      characteristic curve of the volumetric criterion for splenomegaly detection was
      0.96. Using the volumetric thresholds as the reference standard, the sensitivity
      of radiologists in detecting all/mild/massive splenomegaly was 95.0/66.6/99.0% at
      78.0% specificity, respectively. CONCLUSION: Thresholds for the identification
      and grading of splenomegaly from automatic volumetric spleen assessment were
      introduced. The volumetric thresholds match well with clinical interpretations
      for splenomegaly and may improve splenomegaly detection compared with splenic
      cephalocaudal height measurements or visual inspection commonly used in current
      clinical practice.

PMID- 23535192
TI  - Reliability and validity of soft copy images based on flat-panel detector in
      pneumoconiosis classification: comparison with the analog radiographs.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the reliability
      and validity of soft copy images based on flat-panel detector of digital
      radiography (DR-FPD soft copy images) compared to analog radiographs (ARs) in
      pneumoconiosis classification and diagnosis. MATERIALS AND METHODS: DR-FPD soft
      copy images and ARs from 349 subjects were independently read by four-experienced
      readers according to the International Labor Organization 2000 guidelines. DR-FPD
      soft copy images were used to obtain consensus reading (CR) by all readers as the
      gold standard. Reliability and validity were evaluated by a kappa and receiver
      operating characteristic analysis, respectively. RESULTS: In small opacity,
      overall interreader agreement of DR-FPD soft copy images was significantly higher
      than that of ARs, but it was not significantly different in large opacity and
      costophrenic angle obliteration. In small opacity, agreement of DR-FPD soft copy
      images with CR was significantly higher than that of ARs with CR. It was also
      higher than that of ARs with CR in pleural plaque and thickening. Receiver
      operating characteristic areas were not different significantly between DR-FPD
      soft copy images and ARs. CONCLUSIONS: DR-FPD soft copy images showed accurate
      and reliable results in pneumoconiosis classification and diagnosis compared to
      ARs.

PMID- 23535193
TI  - ZnT8 antibodies in patients with cystic fibrosis: an expression of secondary beta
      cell damage?
AB  - Cystic Fibrosis-Related Diabetes (CFRD) is caused by a severe insulin deficiency
      with associated different degrees of insulin resistance. Data concerning the
      potential impact of autoimmunity are conflicting. Ninety subjects with cystic
      fibrosis (CF) were tested for glucose tolerance and autoantibodies against
      insulin (IAA), glutamic acid decarboxylase (GADA), protein tyrosine phosphatase
      (IA2) and zinc transporter 8 (Znt8A). Eighty-three subjects showed a normal
      glucose tolerance (92.2%), 6 subjects (6.6%) impaired glucose tolerance and 1
      subject (1.1%) newly diagnosed CFRD. Four subjects were found positive for both
      IAA and GADA (4.4%), one subject (1.1%) for both IA2 and GADA, and one subject
      (1.1%) for isolated GADA. Three subjects (3.3%) showed isolated ZnT8A positivity.
      ZnT8A positivity in CF patients is uncommon and not associated with other
      autoantibodies. ZnT8A may not represent a specific indicator of a primary
      autoimmune beta-cell destruction, but possibly the expression of a secondary
      damage of the pancreatic islets with autoantigen release. 

PMID- 23535194
TI  - Parameter uncertainty in biochemical models described by ordinary differential
      equations.
AB  - Improved mechanistic understanding of biochemical networks is one of the driving
      ambitions of Systems Biology. Computational modeling allows the integration of
      various sources of experimental data in order to put this conceptual
      understanding to the test in a quantitative manner. The aim of computational
      modeling is to obtain both predictive as well as explanatory models for complex
      phenomena, hereby providing useful approximations of reality with varying levels
      of detail. As the complexity required to describe different system increases, so
      does the need for determining how well such predictions can be made. Despite
      efforts to make tools for uncertainty analysis available to the field, these
      methods have not yet found widespread use in the field of Systems Biology.
      Additionally, the suitability of the different methods strongly depends on the
      problem and system under investigation. This review provides an introduction to
      some of the techniques available as well as gives an overview of the state-of-the
      art methods for parameter uncertainty analysis. 

PMID- 23535195
TI  - Difference in clinical and angiographic characteristics of very late stent
      thrombosis between drug-eluting and bare-metal stent implantations.
AB  - BACKGROUND:  Limited data are available with which to compare the clinical
      characteristics of patients with very late stent thrombosis (VLST) after drug
      eluting stent (DES) or bare-metal stent (BMS) implantation. The purpose of this
      study was to investigate the differences in the characteristics of VLST after DES
      and BMS implantation by reviewing the clinical and angiographic data. METHODS AND
      RESULTS:  A total of 28 patients (30 lesions) with VLST after DES implantation
      and 33 patients (33 lesions) with VLST after BMS implantation were identified.
      The occurrence of VLST after BMS implantation (2,647+/-996 days) was much later
      than that after DES implantation (1,194+/-558 days, P<0.001). The number of VLST
      after DES implantation increased gradually each year; however VLST after BMS
      implantation started to occur >50 months later, and its number increased
      subsequently. The prevalence of VLST related to surgical procedures involving
      discontinuation of antiplatelet therapy in VLST patients was higher after DES
      implantation (14.3%) than after BMS implantation (0%, P=0.039). Angiographic
      stent fracture was seen in 36.7% of VLST lesions after DES implantation at
      different times (464-2,102 days after procedure), while none was seen in VLST
      lesions after BMS implantation (P<0.001). CONCLUSIONS:  The timing of VLST was
      different after DES and BMS implantation. Stent fracture was a specific finding
      of VLST after DES implantation. 

PMID- 23535196
TI  - Vaporizing thrombus with excimer laser before coronary stenting improves
      myocardial reperfusion in acute coronary syndrome.
AB  - BACKGROUND:  Mechanical reperfusion has proven to be an unquestionably superior
      treatment strategy over that of thrombolytic therapy in patients with acute
      coronary syndrome (ACS). Excimer laser coronary angioplasty (ELCA) is a unique
      revascularization device that has a lytic effect on thrombus, in addition to its
      debulking effect on the atherosclerotic plaque beneath the thrombus. METHODS AND
      RESULTS:  This single-center retrospective analysis consisted of consecutive ACS
      patients treated with ELCA (n=50) and age- and sex-matched ACS patients treated
      with manual aspiration (n=48) without use of a distal protection device. Success
      rate was judged by lesion crossability, procedure complications, and significant
      reduction of stenosis. Tissue-level perfusion was assessed on antegrade
      Thrombolysis In Myocardial Infarction (TIMI) flow grade, myocardial blush grade
      (MBG), and ST-segment elevation resolution (STR). Short-term outcome was
      evaluated according to occurrence of in-hospital major adverse cardiac events
      (MACE; myocardial infarction, target lesion revascularization, coronary artery
      bypass graft, and death). Lesion crossability was higher in the ELCA group than
      in the aspiration group (96.2% vs. 82.6%, P=0.04). Attainment of TIMI 3 flow
      (86.0% vs. 68.8%, P=0.04) and MBG 3 (76.0% vs. 54.2%, P=0.02) was also higher in
      the ELCA group than in the aspiration group. Complete STR was similar between the
      2 groups. In-hospital MACE were significantly more frequent in the aspiration
      group. CONCLUSIONS:  ELCA is feasible, safe, and effective for the treatment of
      patients with ACS and appears to be useful as an adjunctive lesion preparation
      device. 

PMID- 23535197
TI  - Significant improvement of left atrial and left atrial appendage function after
      catheter ablation for persistent atrial fibrillation.
AB  - BACKGROUND: The long-term effects of catheter ablation (CA) on the left atrium
      and left atrial appendage (LAA) are unknown in persistent atrial fibrillation
      (AF). This study investigated left atrial (LA) reverse remodeling and evolution
      of LA/LAA function after successful CA for persistent AF and identified
      predictors for maintenance of sinus rhythm (SR) and LA reverse remodeling.
      METHODS AND RESULTS: CA was performed in 123 patients with persistent AF. LA
      volumes, LA strain and LAA wall velocity were assessed both at baseline and at 12
      months after ablation. Patients who maintained SR were divided into 2 groups
      according to whether LA volume decreased by >=15% at follow-up (responders) or
      not (non-responders). During a follow-up period of 18+/-2 months, AF recurred in
      45 patients (37%). Of the remaining 78 patients (63%) without recurrent AF, 62
      patients (79%) were classified as responders. LA/LAA function significantly
      improved and the prevalence of spontaneous echo contrast decreased only in
      responders at follow-up. LA systolic strain and LAA wall velocity were
      independent predictors of both maintenance of SR (odds ratio [OR], 2.57; P=0.003;
      OR, 3.02; P=0.002, respectively) and LA reverse remodeling (OR, 4.44; P=0.007;
      OR, 3.52; P=0.01, respectively). CONCLUSIONS: Successful CA is associated with LA
      reverse remodeling and LA/LAA functional recovery in patients with persistent AF.
      LA systolic strain and LAA wall velocity at baseline predicted both maintenance
      of SR and LA reverse remodeling.

PMID- 23535198
TI  - Blood wastage reduction: a 10-year observational evaluation in a large teaching
      institution in France.
AB  - CONTEXT: Blood transfusion has increased significantly during the last decade and
      blood wastage reduction is a medical and economic challenge in hospital practice
      and for institutional quality, particularly in the ICU and operating theatre.
      OBJECTIVE: To evaluate the impact of multiple strategies in one hospital to
      reduce red blood cell wastage. DESIGN: Multicentre, prospective, comparative,
      observational study. SETTING: Over 10 years, the study was conducted over two
      time periods. During the first period (2000 to 2003), information was given to
      medical professionals about blood wastage, and audits (reasons for wastage) were
      performed, in a large teaching institution (more than 4% wastage in 1999). The
      second period (2004 to 2010) was designed to analyse the impact of seven
      strategies intended to minimise blood wastage. Blood wastage reduction in the
      local centre was compared with regional (64 institutions) and national centres
      (1470 institutions). Reduction was compared using the Mann-Kendall non-parametric
      trend test. PATIENTS: Local centre (22,572 transfused patients, Nimes, France),
      regional centre (South France, 64 institutions, 208,525 transfused patients) and
      national centres (France, 1470 institutions). INTERVENTIONS: Medical and surgical
      procedures. MAIN OUTCOME MEASURES: The primary end-point was to describe the
      percentage of blood wastage for two periods in a local centre. The secondary
      objective was to compare the percentage of blood wastage in the local centre with
      wastage at regional and national centres. RESULTS: Over the 10 year study period
      the percentage of blood wastage in the local centre decreased, with a significant
      reduction in the second period, from more than 4% (1999) to less than 1% (2010; P
      < 0.05). Blood wastage at regional and national centres was never less than 1%.
      Inadequate containers for transport, absence of a temperature analyser in the ICU
      and inadequate intraoperative blood strategies (excessive orders of blood) were
      the main causes of wastage. Correction of these points affected the outcome
      favourably in the second period, but transfusion information was poor in the
      first period. CONCLUSION: Seven simple strategies (including transport containers
      with an effective temperature analyser and audits) decreased blood wastage,
      especially in the ICU and operating theatre.

PMID- 23535199
TI  - A novel HLA allele, HLA-C*01:02:18, was identified by polymerase chain reaction
      sequence-based typing in a Chinese leukemia patient.
AB  - HLA-C*01:02:18 shows one nucleotide difference from that of HLA-C*01:02:01 by a
      single nucleotide substitution at position 474 C>T in exon 3.

PMID- 23535200
TI  - Decreased perception of bourgeonal may be linked to male idiopathic infertility.
AB  - Regarding the chemotaxis of sperms, new insights have been gained during the last
      20 years. Olfactory receptors are expressed on the flagellar midpiece of human
      spermatogenic cells. One of them, OR1D2, is also expressed in the olfactory
      epithelium. This receptor has been suggested to play a role in sperm chemotaxis
      and thus in fertility. As OR1D2 is activated by bourgeonal, the aim of the study
      was to investigate whether patients with idiopathic infertility would exhibit a
      decreased olfactory sensitivity toward bourgeonal. Participants were 14 patients
      with idiopathic infertility and 23 controls (all young fathers). After having
      ascertained normosmia, odor thresholds and intensity ratings for the pleasant and
      flowery odors of bourgeonal, helional, and phenylethylalcohol were obtained. As a
      result, patients had specifically decreased intensity ratings for bourgeonal. It
      suggests that men with unexplained infertility tend to be less suprathreshold
      sensitive toward the odor of bourgeonal but not to that of other floral odors. It
      may be speculated that the decreased olfactory sensitivity relates to a decreased
      functionality of OR1D2, which in turn may be linked to idiopathic infertility.

PMID- 23535201
TI  - In vivo monitoring of distributional transport kinetics and extravasation of
      quantum dots in living rat liver.
AB  - Although the unique optical properties of surface-modified quantum dots (QDs)
      have attracted wide interest in molecular biology and bioengineering, there are
      very few reports of their in vivo biodistribution, due to a lack of analytical
      techniques for characterizing the dynamic variation of QDs in living animals. In
      this study, we used an in vivo online monitoring system and a batch-wise
      elemental analytical method to investigate the biodistribution/extravasation of
      various surface-modified CdTeSe/ZnS (QDs) in rat liver. It is found that the
      surface modification dictated not only the blood retention profile but also the
      degree of extravasation and the clearance of extracellular QDs, making it an
      important variable for regulating the transfer and exchange process of QDs among
      three physiological compartments-bloodstream, extracellular space and Kupffer
      cells/hepatocytes.

PMID- 23535203
TI  - Neuroimaging of dementias.

PMID- 23535202
TI  - PKA: lessons learned after twenty years.
AB  - The first protein kinase structure, solved in 1991, revealed the fold that is
      shared by all members of the eukaryotic protein kinase superfamily and showed how
      the conserved sequence motifs cluster mostly around the active site. This
      structure of the PKA catalytic (C) subunit showed also how a single phosphate
      integrated the entire molecule. Since then the EPKs have become a major drug
      target, second only to the G-protein coupled receptors. Although PKA provided a
      mechanistic understanding of catalysis that continues to serve as a prototype for
      the family, by comparing many active and inactive kinases we subsequently
      discovered a hydrophobic spine architecture that is a characteristic feature of
      all active kinases. The ways in which the regulatory spine is dynamically
      assembled is the defining feature of each protein kinase. Protein kinases have
      thus evolved to be molecular switches, like the G-proteins, and unlike metabolic
      enzymes which have evolved to be efficient catalysis. PKA also shows how the
      dynamic tails surround the core and serve as essential regulatory elements. The
      phosphorylation sites in PKA, introduced both co- and post-translationally, are
      very stable. The resulting C-subunit is then packaged as an inhibited holoenzyme
      with cAMP-binding regulatory (R) subunits so that PKA activity is regulated
      exclusively by cAMP, not by the dynamic turnover of an activation loop phosphate.
      We could not understand activation and inhibition without seeing structures of
      R:C complexes; however, to appreciate the structural uniqueness of each R2:C2
      holoenzyme required solving structures of tetrameric holoenzymes. It is these
      tetrameric holoenzymes that are localized to discrete sites in the cell,
      typically by A Kinase Anchoring Proteins where they create discrete foci for PKA
      signaling. Understanding these dynamic macromolecular complexes is the challenge
      that we now face. This article is part of a Special Issue entitled: Inhibitors of
      Protein Kinases (2012).

PMID- 23535204
TI  - The time-efficiency principle: time as the key diagnostic strategy in primary
      care.
AB  - The test and retest opportunity afforded by reviewing a patient over time
      substantially increases the total gain in certainty when making a diagnosis in
      low-prevalence settings (the time-efficiency principle). This approach safely and
      efficiently reduces the number of patients who need to be formally tested in
      order to make a correct diagnosis for a person. Time, in terms of observed
      disease trajectory, provides a vital mechanism for achieving this task. It
      remains the best strategy for delivering near-optimal diagnoses in low-prevalence
      settings and should be used to its full advantage. 

PMID- 23535205
TI  - A new factor influencing pathogen detection by molecular assay in children with
      both mild and severe hand, foot, and mouth disease.
AB  - This study aimed to find novel information concerning pathogen detection and some
      probable coinfection factors in hand, foot, and mouth disease (HFMD). In this
      study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71
      (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were
      examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or
      reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD
      patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe
      patients were detected. Our results indicated that the severity of HFMD may
      affect the pathogen detection. The lower positive rates of enterovirus and
      respiratory viruses in severe HFMD cases by RT-PCR were probably related to
      stronger immune response. Therefore, immunological tests such as ELISA are
      essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in
      HFMD, especially in severe cases.

PMID- 23535206
TI  - A simple and sensitive quality control method of the anaerobic atmosphere for
      identification and antimicrobial susceptibility testing of anaerobic bacteria.
AB  - The maintenance of a strict anaerobic atmosphere is essential for the culture of
      strict anaerobic bacteria. We describe a simple and sensitive quality control
      method of the anaerobic atmosphere, based on the measurement of the zone diameter
      around a 5-MUg metronidazole disk when testing an aerotolerant Clostridium
      perfringens strain. A zone diameter above 27 mm was indicative of acceptable
      anaerobic conditions.

PMID- 23535207
TI  - Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid
      abnormalities in an immunocompetent adolescent: a case report.
AB  - A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare
      complication of infectious mononucleosis. The severe clinical picture and the
      marked neuroimaging changes were in contrast with mild cerebrospinal fluid
      abnormalities: leukocyte count was normal and protein level was only slightly
      elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain
      reaction.

PMID- 23535208
TI  - Antimicrobial activity of ceftaroline and comparator agents tested against
      bacterial isolates causing skin and soft tissue infections and community-acquired
      respiratory tract infections isolated from the Asia-Pacific region and South
      Africa (2010).
AB  - Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a
      cephalosporin with in vitro bactericidal activity against resistant Gram-positive
      organisms including methicillin-resistant Staphylococcus aureus (MRSA) and
      multidrug-resistant strains of Streptococcus pneumoniae, and common Gram-negative
      organisms, including wild-type Enterobacteriaceae. We evaluated the in vitro
      activity of ceftaroline and selected comparator agents against bacterial isolates
      collected from patients with skin and soft tissue infections (SSTI) and community
      acquired respiratory tract infections (CARTI) in the Asia-Pacific region and
      South Africa. A total of 2351 isolates, 1100 from SSTI and 1251 from CARTI, were
      collected from 25 medical centers distributed across 8 countries as part of the
      2010 AWARE ceftaroline surveillance program and tested for susceptibility by
      reference broth microdilution methods. Ceftaroline was very active against S.
      aureus (MIC50/90, 0.25/1 MUg/mL; 93.4% susceptible), including MRSA (MIC50/90,
      1/2 MUg/mL; 80.6% susceptible). Against beta-hemolytic streptococci, ceftaroline
      demonstrated greater activity (MIC90, 0.015 MUg/mL) than penicillin (MIC90, 0.06
      MUg/mL). Ceftaroline was also highly active against viridans group streptococci
      (MIC90, 0.12 MUg/mL). Similarly to ceftriaxone, ceftaroline activity against
      Escherichia coli (MIC50/90, >32/>32 MUg/mL) and Klebsiella spp. (MIC50/90,
      0.12/>32 MUg/mL) was compromised by the high prevalence of isolates with an ESBL
      phenotype in the region, particularly in China. Ceftaroline was the most potent
      beta-lactam tested against S. pneumoniae (MIC50/90 of 0.015/0.25 MUg/mL; 99.8%
      susceptible by Clinical and Laboratory Standards Institute [CLSI] criteria), and
      it was also highly potent against Haemophilus influenzae (MIC50/90, <= 0.008/0.03
      MUg/mL; 100% susceptible by CLSI criteria). Ceftaroline was also active against
      H. parainfluenzae (MIC50/90, <= 0.008/0.015 MUg/mL) and Moraxella catarrhalis
      (MIC50/90, 0.06/0.12 MUg/mL). In summary, ceftaroline showed potent in vitro
      activity against a large collection of bacterial isolates (2351) associated with
      SSTI and CARTI from the Asia-Pacific region and South Africa.

PMID- 23535209
TI  - NIRS during therapeutic hypothermia: cool or hot?

PMID- 23535210
TI  - Ulcerative lesions as a rare cause of laryngotracheitis in the pediatric
      population.
AB  - OBJECTIVE: The goal of this study is to describe a unique finding of ulcerative
      lesions of the larynx in two pediatric patients presenting with prolonged acute
      laryngotracheitis and compare to previously described reports to determine the
      typical clinical picture, need for intervention, and management model. METHODS:
      We present two cases of ulcerative lesions of the larynx in immunocompetent
      children, one with PCR positive HSV, which presented as severe croup requiring
      intensive care unit admission. Literature review was completed to assess for
      current knowledge of this entity. Our cases are discussed in the context of
      previously reported cases of HSV laryngotracheitis. Descriptive analysis was
      completed focusing on presentation, physical exam findings, treatment, length of
      therapy, and outcomes. RESULTS: Literature review uncovered six case reports
      including 10 individual cases of prolonged croup with findings of HSV laryngitis
      and one retrospective review describing 15 cases of prolonged croup found to be
      caused by ulcerative laryngitis. All patients underwent direct laryngoscopy and
      bronchoscopy for evaluation. Analysis was completed comparing the studies to our
      patients with significant findings including high intubation rate of 77%,
      ulcerative stomatitis in 63%, and treatment with antiviral medication directed at
      HSV in 85% with improvement in symptoms. CONCLUSION: It is important to consider
      HSV as a possible pathogen in cases of prolonged or atypical croup. Laryngoscopy
      should be used for diagnostic intervention and identification of ulcerative
      lesions. Stomatitis may be an indication for earlier direct inspection. Treatment
      with anti-viral therapy and with discontinuation or taper of steroid is
      suggested.

PMID- 23535211
TI  - Skeletal muscle molecular responses to resistance training and dietary
      supplementation in COPD.
AB  - BACKGROUND: Skeletal muscle dysfunction is a systemic feature of chronic
      obstructive pulmonary disease (COPD), contributing to morbidity and mortality.
      Physical training improves muscle mass and function in COPD, but the molecular
      regulation therein is poorly understood. METHODS: Candidate genes and proteins
      regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle
      protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of
      rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription
      (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at
      four time points over 8 weeks of knee extensor resistance training (RT) in
      patients with COPD and healthy controls (HCs). Patients with COPD were randomly
      allocated to receive protein/carbohydrate or placebo supplements during RT.
      RESULTS: 59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory
      volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0
      (21.6) % predicted) were enrolled. RT increased lean mass (~5%) and strength
      (~20%) in all groups. Absolute work done during RT was lower throughout in
      patients with COPD compared with HCs. RT resulted in increases (from basal) in
      catabolic, anabolic, myogenic and transcription factor protein expression at 24
      h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients
      with COPD, except for myogenic signalling, which was similar. Nutritional
      supplementation did not augment functional or molecular responses to RT.
      CONCLUSIONS: The potential for muscle rehabilitation in response to RT is
      preserved in COPD. Except for markers of myogenesis, molecular responses to RT
      are not tightly coupled to lean mass gains but reflect the lower work done during
      RT, suggesting some caution when identifying molecular targets for intervention.
      Increasing post-exercise protein and carbohydrate intake is not a prerequisite
      for a normal training response in COPD.

PMID- 23535212
TI  - Effectiveness of influenza vaccination in working-age adults with diabetes: a
      population-based cohort study.
AB  - BACKGROUND: Guidelines recommend influenza vaccinations in all diabetic adults,
      but there is limited evidence to support vaccinating working-age adults (<65
      years) with diabetes. We examined the effectiveness of influenza vaccine in this
      subgroup, compared with elderly adults (>= 65 years) for whom vaccination
      recommendations are well accepted. METHODS: We identified all adults with
      diabetes, along with a sample of age-matched and sex-matched comparison subjects
      without diabetes, from 2000 to 2008, using administrative data from Manitoba,
      Canada. With multivariable Poisson regression, we estimated vaccine effectiveness
      (VE) on influenza-like illnesses (ILIs), pneumonia and influenza (PI)
      hospitalisations and all-cause (ALL) hospitalisations during periods of known
      circulating influenza. Analyses were replicated outside of influenza season to
      rule out residual confounding. RESULTS: We included 543 367 person-years of
      follow-up, during which 223 920 ILI, 5422 PI and 94 988 ALL occurred. The
      majority (58%) of adults with diabetes were working age. In this group, influenza
      vaccination was associated with relative reductions in PI (43%, 95% CI 28% to
      54%) and ALL (28%, 95% CI 24% to 32%) but not ILI (-1%, 95% CI -3% to 1%). VE was
      similar in elderly adults for ALL (33-34%) and PI (45-55%), although not ILI (12
      13%). However, similar estimates of effectiveness were also observed for all
      three groups during non-influenza control periods. CONCLUSIONS: Working-age
      adults with diabetes experience similar benefits from vaccination as elderly
      adults, supporting current diabetes-specific recommendations. However, these
      benefits were also manifest outside of influenza season, suggesting residual
      bias. Vaccination recommendations in all high-risk adults would benefit from
      randomised trial evidence.

PMID- 23535215
TI  - Identification of a novel HLA-A*33:03:11 allele by polymerase chain reaction
      sequence-based typing in a Chinese cord blood donor.
AB  - HLA-A*33:03:11 differs from A*33:03:01 by one nucleotide substitution in exon 3
      at position 531 G>A.

PMID- 23535213
TI  - Programmable plasmid interference by the CRISPR-Cas system in Thermococcus
      kodakarensis.
AB  - CRISPR-Cas systems are RNA-guided immune systems that protect prokaryotes against
      viruses and other invaders. The CRISPR locus encodes crRNAs that recognize
      invading nucleic acid sequences and trigger silencing by the associated Cas
      proteins. There are multiple CRISPR-Cas systems with distinct compositions and
      mechanistic processes. Thermococcus kodakarensis (Tko) is a hyperthermophilic
      euryarchaeon that has both a Type I-A Csa and a Type I-B Cst CRISPR-Cas system.
      We have analyzed the expression and composition of crRNAs from the three CRISPRs
      in Tko by RNA deep sequencing and northern analysis. Our results indicate that
      crRNAs associated with these two CRISPR-Cas systems include an 8-nucleotide
      conserved sequence tag at the 5' end. We challenged Tko with plasmid invaders
      containing sequences targeted by endogenous crRNAs and observed active CRISPR-Cas
      mediated silencing. Plasmid silencing was dependent on complementarity with a
      crRNA as well as on a sequence element found immediately adjacent to the crRNA
      recognition site in the target termed the PAM (protospacer adjacent motif).
      Silencing occurred independently of the orientation of the target sequence in the
      plasmid, and appears to occur at the DNA level, presumably via DNA degradation.
      In addition, we have directed silencing of an invader plasmid by genetically
      engineering the chromosomal CRISPR locus to express customized crRNAs directed
      against the plasmid. Our results support CRISPR engineering as a feasible
      approach to develop prokaryotic strains that are resistant to infection for use
      in industry. 

PMID- 23535216
TI  - Effects of (12)C(6+) ion radiation and ferulic acid on the zebrafish (Danio
      rerio) embryonic oxidative stress response and gene expression.
AB  - The effects of carbon ion irradiation and ferulic acid (FA) on the induction of
      oxidative stress and alteration of gene expression were studied in zebrafish
      (Danio rerio) embryos. Zebrafish embryos at 8 hpf were divided into seven groups:
      the control group; the 1Gy, 3Gy and 7Gy irradiation groups; and three FA-pre
      treated irradiation groups. In the irradiated groups, a significant increase in
      the teratogenesis of the zebrafish embryos and oxidative stress was accompanied
      by increased malondialdehyde (MDA) content, decreased glutathione (GSH) content
      and alterations in antioxidant enzyme activities (such as catalase [CAT] and
      superoxide dismutase [SOD]). Moreover, the mRNA levels for Cu/Zn-sod, Mn-sod, cat
      and gpx, the genes encoding these antioxidant proteins, were altered
      significantly. However, the mRNA expression patterns were not in accordance with
      those of the antioxidant enzymes and were more sensitive under low-dose
      irradiation. In addition, we detected the mRNA expression of ucp-2 and bcl-2,
      which are located at the mitochondrial inner membrane and related to reactive
      oxidative species (ROS) production. In the irradiated groups, the mRNA level of
      ucp-2 was significantly increased, whereas the mRNA level of bcl-2 was
      significantly decreased. Supplementation with FA, an antioxidant, was better able
      to reduce the irradiation-induced oxidative damage marked by changes in
      mortality, morphology, antioxidant enzyme activities and the MDA and GSH content,
      as well as in the mRNA expression levels. Overall, this study provided helpful
      information about the transcriptional effects of irradiation to better understand
      the mechanism of carbon ion-induced oxidative stress and FA-induced
      radioprotective effects.

PMID- 23535217
TI  - Pay attention to valvular disease in the presence of atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common skin condition in which
      Staphylococcus (S.) aureus can cause native valve destruction in patients with
      infective endocarditis (IE). The aim of this study was to determine the early and
      late outcomes of IE and AD. METHODS AND RESULTS: The medical records of patients
      with IE and AD who presented between January 1997 and September 2010 were
      analyzed retrospectively. IE and AD patients were compared with those with IE
      without AD. The mean follow-up period was 5.5+/-3.4 years. The incidence of AD
      among IE patients was 6.7% and they were significantly younger than those without
      AD (28.4 years vs. 53.7 years; P<0.0001). Methicillin-sensitive S. aureus and
      Streptococcus species were more prevalent in IE with AD (P<0.0001) and without AD
      (P=0.0259), respectively. One developed postoperative mediastinitis caused by
      methicillin-resistant S. aureus despite preoperative skin care. None of the
      patients died in hospital or had IE recurrence. Freedom from recurrent IE or
      prosthetic valve endocarditis at 5 years was 100+/-0.0%. CONCLUSIONS: Patients
      with IE must be checked for AD and history of AD because AD patients have a high
      incidence of staphylococcal colonization in their skin lesion.

PMID- 23535218
TI  - Variability of microcirculatory resistance index and its relationship with
      fractional flow reserve in patients with intermediate coronary artery lesions.
AB  - BACKGROUND: The relationship between the functional significance of epicardial
      coronary artery stenosis and microvascular resistance remains to be determined.
      Furthermore, little is known regarding the determinants of microvascular
      resistance in patients with intermediate coronary lesions. METHODS AND RESULTS:
      Using a pressure-temperature sensor-tipped guidewire, thermodilution-derived
      index of microcirculatory resistance (IMR) was measured, along with fractional
      flow reserve (FFR), in 131 coronary arteries of 104 patients with intermediate
      stenosis, in order to determine the relationship between IMR and clinical data.
      IMR varied widely (median, 20.8; range, 6.3-65.2), and no significant
      relationship was observed between IMR and FFR after IMR was corrected for
      coronary wedge pressure in the territories with functionally significant
      stenoses. There was no significant relationship between IMR and Framingham risk
      score, systematic coronary risk evaluation (SCORE), ACC/AHA lesion
      classification, or SYNTAX score. Right coronary artery (RCA) lesion location and
      history of hypertension were significantly associated with increased IMR.
      Multivariate analysis showed that RCA lesion location (odds ratio [OR], 4.52; 95%
      confidence interval [CI]: 1.84-11.11, P=0.001) and hypertension (OR, 3.03; 95%
      CI: 1.15-7.96, P=0.025) were independent predictors of increased IMR.
      CONCLUSIONS: Functional significance of intermediate coronary stenosis was not
      correlated with microvascular resistance of the perfusion territory. Intermediate
      coronary lesions may result in increased microcirculatory resistance irrespective
      of functional significance of the stenosis, with significant regional difference
      in microvascular resistance.

PMID- 23535219
TI  - Hook-like long linear echogenic mobile mass arising in the left ventricular
      outflow tract presenting with orthostatic hypotension and syncope: diagnosis on
      multimodal imaging echocardiography and computed tomography.

PMID- 23535221
TI  - Organized thrombus, disorganized heart.

PMID- 23535220
TI  - Differences in body temperature variability between subjects with and without
      diabetes and predictive value for cardiovascular events.
AB  - BACKGROUND: Differences in regulating factors and the clinical implications of
      body temperature variability (BTV) between subjects with and without diabetes
      have not been clarified to date. METHODS AND RESULTS: In 66 subjects with
      ischemic heart disease (33 with diabetes and 33 without diabetes), BTV, the
      difference between the highest and lowest temperature measurements, and body
      temperature standard deviation (BT SD) were measured from axillary body
      temperature (ABT) records of 3 consecutive days and followed for 16.4+/-8.4
      months. In subjects without diabetes BTV and BT SD were closely associated with
      endothelial function as evaluated on flow-mediated dilation (BTV, R=0.33,
      P=0.026; BT SD, R=0.41, P=0.029), whereas there was a poor association in
      subjects with diabetes. In the absence of an interrelationship between vascular
      function and thermoregulation, the contribution of inflammation to BTV was
      increased in subjects with diabetes (BTV, 0.59+/-0.21 degrees C for C-reactive
      protein [CRP] <0.08 mg/dl vs. 0.79+/-0.28 degrees C for CRP >0.08 mg/dl,
      P=0.014). Event-free survival analysis showed that in subjects with diabetes
      higher BT SD was associated with shorter event-free survival (log-rank P=0.012),
      but this relationship was not found in subjects without diabetes. CONCLUSIONS: In
      subjects with diabetes, the interrelationship between thermoregulation and
      vascular function was disrupted and the effect of inflammation on
      thermoregulation was enhanced, so that BTV had a sufficient predictive value for
      cardiovascular events in diabetic subjects.

PMID- 23535222
TI  - Long-term study of an infection with ranaviruses in a group of edible frogs
      (Pelophylax kl. esculentus) and partial characterization of two viruses based on
      four genomic regions.
AB  - Several edible frogs (Pelophylax kl. esculentus) collected into a single group
      from various ponds in Europe died suddenly with reddening of the skin (legs,
      abdomen) and haemorrhages in the gastrointestinal tract. Ranavirus was detected
      in some of the dead frogs using PCR, and virus was also isolated in cell culture.
      Over the following 3 years, another two outbreaks occurred with low to high
      mortality in between asymptomatic periods. In the first 2 years, the same
      ranavirus was detected repeatedly, but a new ranavirus was isolated in
      association with the second mass-mortality event. The two different ranaviruses
      were characterized based on nucleotide sequences from four genomic regions,
      namely, major capsid protein, DNA polymerase, ribonucleoside diphosphate
      reductase alpha and beta subunit genes. The sequences showed slight variations to
      each other or GenBank entries and both clustered to the Rana esculenta virus (REV
      like) clade in the phylogenetic analysis. Furthermore, a quiescent infection was
      demonstrated in two individuals. By comparing samples taken before and after
      transport and caging in groups it was possible to identify the pond of origin and
      a ranavirus was detected for the first time in wild amphibians in Germany.

PMID- 23535223
TI  - Kidney-protective effects of azelnidipine versus a diuretic in combination with
      olmesartan in hypertensive patients with diabetes and albuminuria: a randomized
      study.
AB  - BACKGROUND: A thiazide diuretic used in combination with benazepril is superior
      to amlodipine plus benazepril in reducing albuminuria in hypertensive patients
      with diabetes. However, calcium channel blockers have diverse characteristics.
      Thus, we investigated whether combining an angiotensin receptor blocker with
      either azelnidipine or a thiazide diuretic produced similar reductions in
      albuminuria in hypertensive diabetic patients for the same levels of blood
      pressure achieved. METHODS: Hypertensive patients with type 2 diabetes and
      albuminuria (30-600 mg/g creatinine) under antihypertensive treatment (mean age
      67.0+/-7.6 years) were instructed to stop all antihypertensive treatment and take
      a combination of olmesartan (20 mg/day) and amlodipine (5 mg/day) for 3 months
      (run-in period). Then, patients were randomly assigned to receive either
      olmesartan plus azelnidipine (16 mg/day; n=71) or olmesartan plus
      trichlormethiazide (1 mg/day; n=72) for an additional 6 months. The primary end
      point was urinary excretion of albumin at 6 months after randomization. RESULTS:
      At the time of randomization, urinary albumin was 116.0 and 107.8 mg/g creatinine
      (geometric mean) in the azelnidipine and diuretic arms, respectively, and was
      reduced to a similar extent [79.8 (95% confidence interval 66.4-96.0) and 89.7
      (74.6-107.7) mg/g creatinine, respectively, after adjustment for baseline
      values]. Blood pressure did not differ between the two groups throughout the
      study period. CONCLUSIONS: Azelnidipine is equally effective as a thiazide
      diuretic in reducing urinary albumin when used in combination with olmesartan.

PMID- 23535224
TI  - Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease.
AB  - BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the
      renin-angiotensin system that counteracts the adverse effects of angiotensin II.
      In heart failure patients, elevated plasma ACE2 activity predicted adverse events
      and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and
      its clinical associations in patients with kidney disease. METHODS: Patients
      recruited from a single centre comprised of chronic kidney disease Stage III/IV
      (CKD), haemodialysis patients and kidney transplant recipients (KTRs). Plasma
      ACE2 enzyme activity was measured using a fluorescent substrate assay in plasma,
      collected at baseline and stored at -80 degrees C. Linear regression was
      performed in both males and females separately to determine the covariates
      associated with log-transformed ACE2. RESULTS: The median (interquartile range)
      plasma ACE2 activity in pmol/mL/min was 15.9 (8.4-26.1) in CKD (n = 59), 9.2 (3.9
      18.2) in haemodialysis (n = 100) and 13.1 (5.7-21.9) in KTR (n = 80; P < 0.01).
      In male haemodialysis patients, ACE2 activity was 12.1 (6.8-19.6) compared with
      4.4 (2.5-10.3) in females (P < 0.01). Log-transformed ACE2 plasma activity was
      associated with post-haemodialysis systolic blood pressure in females [beta
      coefficient 0.04, 95% confidence interval (95% CI) 0.01-0.06, P = 0.006]. In
      males, log-transformed ACE2 plasma activity was associated with B-type
      natriuretic peptide (beta-coefficient 0.39, 95% CI 0.19-0.60, P < 0.001). Plasma
      ACE2 activity was not associated with mortality. CONCLUSIONS: Plasma ACE2
      activity is reduced in haemodialysis patients compared with CKD patients, and in
      female haemodialysis patients compared with male. The different associations of
      plasma ACE2 activity between male and female haemodialysis patients indicate that
      the role of ACE2 in cardiovascular disease may differ by gender.

PMID- 23535225
TI  - Primary aldosteronism and low-renin hypertension: a continuum?

PMID- 23535226
TI  - Diagnostic and management of spontaneous rectus sheath hematoma.
AB  - BACKGROUND: Spontaneous rectus sheath hematoma is an uncommon and often
      misdiagnosed cause of abdominal pain. The aim of this study is to describe our
      experience in their management. METHODS: Retrospective analysis of the
      characteristics and outcomes of the spontaneous rectus sheath hematomas diagnosed
      over the last 12years was conducted. RESULTS: 24 patients were included (66%
      women; mean age: 74years; range: 54-87). All cases presented predisposing factors
      mainly anticoagulant therapy in 21 (87.5%) patients, hypertension in 19 (79.1%)
      and abdominal surgery in 12 (50%) cases. Eighteen (75%) referred triggering
      factors like coughing being the most common one, present in 17 (70.8%) patients.
      The main clinical findings were abdominal pain in 21 (87.5%) cases and the
      existence of an abdominal mass in 20 (83.3%). The diagnosis was confirmed by
      abdominal ultrasonography and/or computerized tomography in 23 (95.8%) patients.
      Nineteen cases (79.1%) responded to conservative management while 5 (20.8%)
      required interventional treatment, which consisted in an arteriography with
      selective embolization of the epigastric arteries in all cases. Four (80%) of the
      patients needing interventional treatment were receiving low molecular weight
      heparin. Nine (37.5%) patients developed hypovolemic shock and 1 (4%) died.
      CONCLUSIONS: Spontaneous rectus sheath hematomas should be considered in the
      differential diagnosis of abdominal pain, particularly in elderly women under
      anticoagulant therapy with onset of symptoms after a bout of cough. Most cases
      respond to conservative management, although those related to low molecular
      weight heparin might require interventional treatment; arteriography with
      selective embolization of the epigastric arteries is the first therapeutic
      option.

PMID- 23535227
TI  - Coeliac disease in a 15-year period of observation (1997 and 2011) in a Hungarian
      referral centre.
AB  - AIMS: The aim of this study is to evaluate the experience of a single coeliac
      centre over a 15-year-long study period (between November of 1997 and September
      of 2011). PATIENTS AND METHODS: Charts of 178 patients (139 females) with coeliac
      disease were retrospectively evaluated. Tests performed: multiple duodenal
      biopsies, anti-tissue transglutaminase and anti-endomysium antibodies, body mass
      index calculation, osteodensitometry, evaluation of disorders associated with
      coeliac disease, and implementation of family screening. RESULTS: Histological
      samples were available in 133 cases, distribution according to Marsh-Oberhuber
      classification: M0 in 7%, M1-M2 in 4%, M3a in 26%, M3b in 13%, and M3c in 50% of
      cases, respectively. Anti-tissue transglutaminase and anti-endomysium antibody
      tests were available in 158 cases, 132/158 showed seropositivity. Mean body mass
      index values were 23.05kg/m(2) for males, and 21.07kg/m(2) for females,
      respectively. Osteodensitometry showed normal values in 46%, osteopenia in 36%,
      and osteoporosis in 18% of cases, respectively. Coeliac disease associated
      disorders was present in 63/178 (35%) patients. Ninety coeliacs brought 197 first
      degree relatives for screening, with 47/197 (23%) relatives proving to have
      coeliac disease. Correlations between anti-tissue transglutaminase antibody
      titres and Marsh-Oberhuber classification, and anti-tissue transglutaminase
      antibody titres and bone mineral density values were found to be statistically
      significant (p=0.0011, and p=0.001, respectively). CONCLUSIONS: Coeliac disease
      can become overt at any age. Female predominance is significant. Histology
      usually showed advanced villous atrophy. Mean body mass index values were within
      normal range. The high prevalence of associated disorders is also noted. The
      prevalence of 24% of coeliac disease among first degree relatives underlines the
      necessity of family screening.

PMID- 23535228
TI  - Genetic and environmental components of carotid artery elasticity: an Italian
      twin study.

PMID- 23535229
TI  - Induction of cyto-protective autophagy by paramontroseite VO2 nanocrystals.
AB  - A variety of inorganic nanomaterials have been shown to induce autophagy, a
      cellular degradation process critical for the maintenance of cellular
      homeostasis. The overwhelming majority of autophagic responses elicited by
      nanomaterials were detrimental to cell fate and contributed to increased cell
      death. A widely held view is that the inorganic nanoparticles, when encapsulated
      and trapped by autophagosomes, may compromise the normal autophagic process due
      to the inability of the cells to degrade these materials and thus they manifest a
      detrimental effect on the well-being of a cell. Here we show that, contrary to
      this notion, nano-sized paramontroseite VO2 nanocrystals (P-VO2) induced cyto
      protective, rather than death-promoting, autophagy in cultured HeLa cells. P-VO2
      also caused up-regulation of heme oxygenase-1 (HO-1), a cellular protein with a
      demonstrated role in protecting cells against death under stress situations. The
      autophagy inhibitor 3-methyladenine significantly inhibited HO-1 up-regulation
      and increased the rate of cell death in cells treated with P-VO2, while the HO-1
      inhibitor protoporphyrin IX zinc (II) (ZnPP) enhanced the occurrence of cell
      death in the P-VO2-treated cells while having no effect on the autophagic
      response induced by P-VO2. On the other hand, Y2O3 nanocrystals, a control
      nanomaterial, induced death-promoting autophagy without affecting the level of
      expression of HO-1, and the pro-death effect of the autophagy induced by Y2O3.
      Our results represent the first report on a novel nanomaterial-induced cyto
      protective autophagy, probably through up-regulation of HO-1, and may point to
      new possibilities for exploiting nanomaterial-induced autophagy for therapeutic
      applications.

PMID- 23535230
TI  - Ultrasound guidance for radial arterial puncture: a randomized controlled trial.
AB  - STUDY OBJECTIVE AND BACKGROUND: Arterial puncture for blood gas analysis is a
      frequent procedure and could be difficult in the emergency setting. The aim of
      the study was to compare ultrasonographically guided arterial radial puncture vs
      conventional sampling. MATERIALS AND METHODS: This is a prospective, randomized
      study. The inclusion criteria are all patients needing arterial blood gas at
      admission in the emergency unit. The exclusion criteria are the following: Hallen
      test positive, local sepsis, local trauma, known sever local arteriopathy,
      refusal of consent by the patient, participation in another study, and cardiac
      arrest. Patients were randomized into 2 groups: radial arterial puncture obtained
      through an ultrasonographically guided technique (group 1) or radial arterial
      puncture by conventional method (group 2). The main objective is the number of
      attempts after enrollment. The secondary objectives are time to success, patient
      satisfaction and pain, and physician satisfaction. Immediate complications were
      collected. Groups were compared with nonparametric analysis. RESULTS: The data
      were usable for 72 of 74 patients included. Lung disease (acute exacerbation of
      chronic obstructive pulmonary disease and pneumonia) at 45% (n = 32) and
      suspicion of pulmonary embolism in 31% (n = 22) were the most common reasons.
      Demographics data were comparable in the 2 groups. In group 1, the number of
      attempts significantly increased (2.35 [1-3] vs 1.66 [1-2] [P = .017]), and the
      sample was 2.4 times longer (132 seconds [50-200] vs 55 [20-65] [P < .01] by
      standard method). There was no significant difference in terms of pain (visual
      analog scale [VAS], 3.6 [2-5] for both groups [P = .743]), patient satisfaction
      (VAS, 7.2 [5-9] vs 6.8 [5-9] [P = .494]), and physician satisfaction (VAS, 6.0
      [3.5-8] vs 6.9 [5-9] [P = .233]). No immediate complications were found in the 2
      groups. CONCLUSION: Ultrasonographically guided arterial puncture increases the
      number and duration of implementations. This technique, however, does not alter
      the patient's pain, the number of immediate complications, or patient and
      physician satisfaction.

PMID- 23535231
TI  - Effect of biologically relevant ions on the corrosion products formed on alloy
      AZ31B: an improved understanding of magnesium corrosion.
AB  - Simulated physiological solutions mimicking human plasma have been utilized to
      study the in vitro corrosion of biodegradable metals. However, corrosion and
      corrosion product formation are different for different solutions with varied
      responses and, hence, the prediction of in vivo degradation behavior is not
      feasible based on these studies alone. This paper reports the role of
      physiologically relevant salts and their concentrations on the corrosion behavior
      of a magnesium alloy (AZ31B) and subsequent corrosion production formation.
      Immersion tests were performed for three different concentrations of Ca(2+),
      HPO4(2-), HCO3(-) to identify the effect of each ion on the corrosion of AZ31B
      assessed at 1, 3 and 10 days. Time-lapse morphological characterization of the
      samples was performed using X-ray computed tomography and scanning electron
      microscopy. The chemical composition of the surface corrosion products was
      determined by electron dispersive X-ray spectroscopy and X-ray diffraction. The
      results show that: (1) calcium is not present in the corrosion product layer when
      only Cl(-) and OH(-) anions are available; (2) the presence of phosphate induces
      formation of a densely packed amorphous magnesium phosphate corrosion product
      layer when HPO4(2-) and Cl(-) are present in solution; (3) octacalcium phosphate
      and hydroxyapatite (HAp) are deposited on the surface of the magnesium alloy when
      HPO4(2-) and Ca(2+) are present together in NaCl solution (this coating limits
      localized corrosion and increases general corrosion resistance); (4) addition of
      HCO3(-) accelerates the overall corrosion rate, which increases with increasing
      bicarbonate concentration; (5) the corrosion rate decreases due to the formation
      of insoluble HAp on the surface when HCO3(-), Ca(2+), and HPO4(2-) are present
      together.

PMID- 23535232
TI  - Vancomycin-modified LaB6@SiO2/Fe3O4 composite nanoparticles for near-infrared
      photothermal ablation of bacteria.
AB  - LaB6 nanoparticles possess excellent near-infrared (NIR) photothermal conversion
      properties. Vancomycin can interact strongly with a broad range of Gram-positive
      and Gram-negative bacteria. Fe3O4 nanoparticles could be used as the carrier for
      magnetic separation. In this work, vancomycin and Fe3O4 nanoparticles were
      successfully bound onto the surface of LaB6 nanoparticles with a silica coating
      and carboxyl functionalization to fabricate vancomycin-modified LaB6@SiO2/Fe3O4
      (Van-LaB6@SiO2/Fe3O4) composite nanoparticles as a novel nanomaterial for the NIR
      photothermal ablation of bacteria. From the analyses of absorption spectra,
      transmission electron microscopy images and X-ray diffraction patterns, the
      formation of Van-LaB6@SiO2/Fe3O4 composite nanoparticles was confirmed. The
      resulting Van-LaB6@SiO2/Fe3O4 composite nanoparticles possessed nearly
      superparamagnetic properties, retained the excellent NIR photothermal conversion
      property of LaB6 nanoparticles and could capture the bacteria Staphylococcus
      aureus and Escherichia coli efficiently. Owing to these capabilities, they were
      demonstrated to be quite efficient for the magnetic separation and NIR
      photothermal ablation of S. aureus and E. coli. Furthermore, the magnetic
      property made the Van-LaB6@SiO2/Fe3O4 composite nanoparticles useful for the
      magnetic assembling of bacteria, which could further enhance the photothermal
      ablation efficiency.

PMID- 23535234
TI  - Repair of an articular cartilage defect using adipose-derived stem cells loaded
      on a polyelectrolyte complex scaffold based on poly(l-glutamic acid) and
      chitosan.
AB  - As a synthetic polypeptide water-soluble poly(l-glutamic acid) (PLGA) was
      designed to fabricate scaffolds for cartilage tissue engineering. Chitosan (CHI)
      has been employed as a physical cross-linking component in the construction of
      scaffolds. PLGA/CHI scaffolds act as sponges with a swelling ratio of 760+/-45%
      (mass%), showing promising biocompatibility and biodegradation. Autologous
      adipose-derived stem cells (ASCs) were expanded and seeded on PLGA/CHI scaffolds,
      ASC/scaffold constructs were then subjected to chondrogenic induction in vitro
      for 2weeks. The results showed that PLGA/CHI scaffolds could effectively support
      ASC adherence, proliferation and chondrogenic differentiation. The ASCs/scaffold
      constructs were then transplanted to repair full thickness articular cartilage
      defects (4mm in diameter, to the depth of subchondral bone) created in rabbit
      femur trochlea. Histological observations found that articular defects were
      covered with newly formed cartilage 6weeks post-implantation. After 12weeks the
      regenerated cartilage had integrated well with the surrounding native cartilage
      and subchondral bone. Toluidine blue and immunohistochemical staining confirmed
      similar accumulation of glycosaminoglycans and type II collagen in engineered
      cartilage as in native cartilage 12weeks post-implantation. The result was
      further supported by quantitative analysis of extracellular matrix deposition.
      The compressive modulus of the engineered cartilage increased significantly from
      30% of that of normal cartilage at 6weeks to 83% at 12weeks. Cyto-nanoindentation
      also showed analogous biomechanical behavior of the engineered cartilage to that
      of native cartilage. The results of the present study thus demonstrate the
      potentiality of PLGA/CHI scaffolds in cartilage tissue engineering.

PMID- 23535233
TI  - Acoustic droplet-hydrogel composites for spatial and temporal control of growth
      factor delivery and scaffold stiffness.
AB  - Wound healing is regulated by temporally and spatially restricted patterns of
      growth factor signaling, but there are few delivery vehicles capable of the "on
      demand" release necessary for recapitulating these patterns. Recently we
      described a perfluorocarbon double emulsion that selectively releases a protein
      payload upon exposure to ultrasound through a process known as acoustic droplet
      vaporization (ADV). In this study, we describe a delivery system composed of
      fibrin hydrogels doped with growth factor-loaded double emulsion for applications
      in tissue regeneration. Release of immunoreactive basic fibroblast growth factor
      (bFGF) from the composites increased up to 5-fold following ADV and delayed
      release was achieved by delaying exposure to ultrasound. Releasates of ultrasound
      treated materials significantly increased the proliferation of endothelial cells
      compared to sham controls, indicating that the released bFGF was bioactive. ADV
      also triggered changes in the ultrastructure and mechanical properties of the
      fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated
      composites were accompanied by up to a 22-fold increase in shear stiffness. ADV
      did not reduce the viability of cells suspended in composite scaffolds. These
      results demonstrate that an acoustic droplet-hydrogel composite could have broad
      utility in promoting wound healing through on-demand control of growth factor
      release and/or scaffold architecture.

PMID- 23535235
TI  - Fabrication and characterization of monodisperse PLGA-alginate core-shell
      microspheres with monodisperse size and homogeneous shells for controlled drug
      release.
AB  - Monodisperse PLGA-alginate core-shell microspheres with controlled size and
      homogeneous shells were first fabricated using capillary microfluidic devices for
      the purpose of controlling drug release kinetics. Sizes of PLGA cores were
      readily controlled by the geometries of microfluidic devices and the fluid flow
      rates. PLGA microspheres with sizes ranging from 15 to 50MUm were fabricated to
      investigate the influence of the core size on the release kinetics. Rifampicin
      was loaded into both monodisperse PLGA microspheres and PLGA-alginate core-shell
      microspheres as a model drug for the release kinetics studies. The in vitro
      release of rifampicin showed that the PLGA core of all sizes exhibited sigmoid
      release patterns, although smaller PLGA cores had a higher release rate and a
      shorter lag phase. The shell could modulate the drug release kinetics as a buffer
      layer and a near-zero-order release pattern was observed when the drug release
      rate of the PLGA core was high enough. The biocompatibility of PLGA-alginate core
      shell microspheres was assessed by MTT assay on L929 mouse fibroblasts cell line
      and no obvious cytotoxicity was found. This technique provides a convenient
      method to control the drug release kinetics of the PLGA microsphere by delicately
      controlling the microstructures. The obtained monodisperse PLGA-alginate core
      shell microspheres with monodisperse size and homogeneous shells could be a
      promising device for controlled drug release.

PMID- 23535236
TI  - Functional small RNAs are generated from select miRNA hairpin loops in flies and
      mammals.
AB  - In the canonical animal microRNA (miRNA) pathway, Drosha generates ~60- to 70
      nucleotide pre-miRNA hairpins that are cleaved by Dicer into small RNA duplexes
      that load into Argonaute proteins, which retain a single mature strand in the
      active complex. The terminal loops of some miRNA hairpins regulate processing
      efficiency, but once liberated by Dicer, they are generally considered
      nonfunctional by-products. Here, we show that specific miRNA loops accumulate in
      effector Argonaute complexes in Drosophila and mediate miRNA-type repression.
      This was unexpected, since endogenous loading of Argonaute proteins was believed
      to occur exclusively via small RNA duplexes. Using in vitro assays, which
      recapitulate Argonaute-specific loop loading from synthetic pre-miRNAs and even
      single-stranded oligoribonucleotides corresponding to miRNA loops, we reveal that
      the loop-loading mechanism is distinct from duplex loading. We also show that
      miRNA loops loaded into the miRNA effector AGO1 are subject to 3' resection, and
      structure-function analyses indicate selectivity of loop loading. Finally, we
      demonstrate that select miRNA loops in mammals are similarly loaded into
      Argonaute complexes and direct target repression. Altogether, we reveal a
      conserved mechanism that yields functional RNAs from miRNA loop regions,
      broadening the repertoire of Argonaute-dependent regulatory RNAs and providing
      evidence for functionality of endogenous ssRNA species.

PMID- 23535237
TI  - Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-activated
      protein kinase and extracellular signal-regulated kinase 1/2 signaling.
AB  - Brain ANG II plays an important role in modulating sympathetic function and
      homeostasis. The generation and degradation of ANG II are carried out, to a large
      extent, through the angiotensin-converting enzyme (ACE) and ACE2, respectively.
      In disease states, such as hypertension and chronic heart failure, central
      expression of ACE is upregulated and ACE2 is decreased in central
      sympathoregulatory neurons. In this study, we determined the expression of ACE
      and ACE2 in response to ANG II in a neuronal cell culture and the subsequent
      signaling mechanism(s) involved. A mouse catecholaminergic neuronal cell line
      (CATH.a) was treated with ANG II (30, 100, and 300 nM) for 24 h, and protein
      expression was determined by Western blot analysis. ANG II induced a significant
      dose-dependent increase in ACE and decrease in ACE2 mRNA and protein expression
      in CATH.a neurons. This effect was abolished by pretreatment of the cells with
      the p38 MAPK inhibitor SB-203580 (10 MUM) 30 min before administration of ANG II
      or the ERK1/2 inhibitor U-0126 (10 MUM). These data suggest that ANG II increases
      ACE and attenuates ACE2 expression in neurons via the ANG II type 1 receptor, p38
      MAPK, and ERK1/2 signaling pathways.

PMID- 23535238
TI  - Impact of robotic operative efficiency on profitability.
AB  - OBJECTIVE: We sought to determine the impact of robotic operative efficiency on
      profitability and assess the impact of secondary variables. STUDY DESIGN:
      Financial data were collected for all robotic cases performed for fiscal years
      2010 (FY10) and 2011 (FY11) at University of North Carolina at Chapel Hill, and
      included 9 surgical subspecialties. Profitability was defined as a positive
      operating income. RESULTS: From July 2009 through June 2011, 1295 robotic cases
      were performed. Robotic surgery was profitable in both fiscal years, with an
      operating income of $386,735 in FY10 and $822,996 in FY11. In FY10, urogynecology
      and pediatric surgery were the only nonprofitable subspecialties. In FY11, all
      subspecialties were profitable. Profitability was associated with case time,
      payor mix, and procedure type (all P < .05). Urogynecology case time decreased
      from 220-179 minutes (P = .012) and pediatric surgery from 418-258 minutes (P =
      .019). CONCLUSION: Robotic operative efficiency has a large impact on overall
      profitability regardless of surgical specialty.

PMID- 23535239
TI  - Implementing an obstetric triage acuity scale: interrater reliability and patient
      flow analysis.
AB  - A 5-category Obstetric Triage Acuity Scale (OTAS) was developed with a
      comprehensive set of obstetrical determinants. The objectives of this study were
      as follows: (1) to test the interrater reliability of OTAS and (2) to determine
      the distribution of patient acuity and flow by OTAS level. To test the interrater
      reliability, 110 triage charts were used to generate vignettes and the
      consistency of the OTAS level assigned by 8 triage nurses was measured. OTAS
      performed with substantial (Kappa, 0.61 - 0.77, OTAS 1-4) and near perfect
      correlation (0.87, OTAS 5). To assess patient flow, the times to primary and
      secondary health care provider assessments and lengths of stay stratified by
      acuity were abstracted from the patient management system. Two-thirds of triage
      visits were low acuity (OTAS 4, 5). There was a decrease in length of stay
      (median [interquartile range], minutes) as acuity decreased from OTAS 1 (120.0
      [156.0] minutes) to OTAS 3 (75.0 [120.8]). The major contributor to length of
      stay was time to secondary health care provider assessment and this did not
      change with acuity. The percentage of patients admitted to the antenatal or
      birthing unit decreased from 80% (OTAS 1) to 12% (OTAS 5). OTAS provides a
      reliable assessment of acuity and its implementation has allowed for triaging of
      obstetric patients based on acuity, and a more in-depth assessment of the patient
      flow. By standardizing assessment, OTAS allows for opportunities to improve
      performance and make comparisons of patient care and flow across organizations. 

PMID- 23535240
TI  - Metabolomic analysis for first-trimester trisomy 18 detection.
AB  - OBJECTIVE: The purpose of this study was to determine whether nuclear magnetic
      resonance-based metabolomic markers in first-trimester maternal serum can detect
      fetuses with trisomy 18. STUDY DESIGN: This was a study of pregnancies between 11
      weeks and 13 weeks 6 days' gestation. We analyzed 30 cases of trisomy 18 and a
      total of 114 euploid cases. Nuclear magnetic resonance-based metabolomic analysis
      was performed. A further analysis was performed that compared 30 cases with
      trisomy 18 and 30 trisomy 21 (T21) cases. RESULTS: Metabolomic markers were
      sensitive for trisomy 18 detection. A combination of 2-hydroxybutyrate, glycerol
      and maternal age had a 73.3% sensitivity and 96.6% specificity for trisomy 18
      detection, with an area under the receiver operating curve: 0.92 (P < .001).
      Other metabolite markers, which include trimethylamine, were sensitive for
      distinguishing trisomy 18 from T21 cases. CONCLUSION: This is the first report of
      prenatal trisomy 18 detection that has been based on metabolomic analysis.
      Preliminary results suggest that such markers are sensitive not only for the
      detection of fetal trisomy 18 but also for distinguishing this aneuploidy from
      T21.

PMID- 23535241
TI  - Neurofibromatosis type 1 and pregnancy complications: a population-based study.
AB  - OBJECTIVE: The objective of the study was to determine whether vascular and other
      complications are more common in pregnant women with neurofibromatosis type 1
      (NF1). STUDY DESIGN: We performed a population-based retrospective cohort study
      using the US Nationwide Inpatient Sample, 1988-2009, defining a cohort of
      pregnancy-related hospitalizations with an associated diagnosis of NF1 and
      comparing it with the control group not associated with NF1. Multivariable
      logistic regression was used to adjust for suspected confounders. RESULTS: Among
      19 million pregnancy-related admissions between 1988 and 2009, we identified 1553
      associated with NF1 (prevalence 0.008%). A diagnosis of NF1 in delivering mothers
      was associated with gestational hypertension (adjusted odds ratio [AOR], 1.6, 95%
      confidence interval [CI], 1.2-2.0), preeclampsia (AOR, 2.8, 95% CI, 2.3-3.4),
      intrauterine growth restriction (AOR, 4.6, 95% CI, 3.7-5.6), cerebrovascular
      disease (OR, 8.1, 95% CI, 2.6-25.4), preterm labor (AOR, 1.6, 95% CI, 1.4-1.9),
      and cesarean delivery (AOR, 2.0, 95% CI, 1.8-2.3). Women with NF1 were not
      significantly more likely to have deep venous thrombosis/pulmonary embolism,
      acute cardiac events, or stillbirth or to die during their hospitalizations
      compared with the general obstetric population. CONCLUSION: NF1 was associated
      with increased maternal morbidity in pregnancy (including hypertensive and
      cerebrovascular complications) but not increased maternal mortality.
      Obstetricians should be aware of the potential for increased antenatal and
      peripartum complications among women with NF1.

PMID- 23535242
TI  - Alerting effects of short-wavelength (blue) and long-wavelength (red) lights in
      the afternoon.
AB  - Light has an acute effect on neuroendocrine responses, performance, and
      alertness. Most studies to date have linked the alerting effects of light to its
      ability to suppress melatonin, which is maximally sensitive to short-wavelength
      light. Recent studies, however, have shown alerting effects of white or
      narrowband short-wavelength lights during daytime, when melatonin levels are low.
      While the use of light at night to promote alertness is well understood, it is
      important to develop an understanding of how light impacts alertness during the
      daytime, especially during the post-lunch hours. The aim of the current study was
      to investigate how 48-minute exposures to short-wavelength (blue) light (40 lux,
      18.9 microWatts/cm(2) lambda(max) = 470 nanometers [nm]) or long-wavelength (red)
      light (40 lux, 18.9 microWatts/cm(2) lambda(max) = 630 nm) close to the post
      lunch dip hours affect electroencephalogram measures in participants with regular
      sleep schedules. Power in the alpha, alpha theta, and theta ranges was
      significantly lower (p<0.05) after participants were exposed to red light than
      after they remained in darkness. Exposure to blue light reduced alpha and alpha
      theta power compared to darkness, but these differences did not reach statistical
      significance (p>0.05). The present results extend those performed during the
      nighttime, and demonstrate that light can be used to increase alertness in the
      afternoon, close to the post-lunch dip hours. These results also suggest that
      acute melatonin suppression is not needed to elicit an alerting effect in humans.

PMID- 23535244
TI  - Ameliorative effects of brief daily periods of social interaction on isolation
      induced behavioral and hormonal alterations.
AB  - The present study investigated the effects of brief daily periods of social
      interaction on social-isolation-induced behavioral and hormonal alterations and
      deficits. Adult male Wistar rats were allocated to one of three housing
      conditions: 1) social housing (two per cage); 2) social isolation (one per cage);
      or partial social isolation (one per cage with access to another male rat for 60
      min/day). After 14 days in these different housing conditions, the animals were
      subjected to various behavioral tests, including sucrose preference test,
      acoustic startle response, two-way active shuttle avoidance, pre-pulse
      inhibition, open field, cooperation learning task, and levels of corticosterone.
      Results revealed that social isolation had a substantial impact on rats'
      performance on most behavioral tests as well as on their corticosterone levels.
      Importantly, however, the results clearly demonstrate that allowing otherwise
      isolated animals to have a brief (60 min) daily social contact with another rat
      to a great extent abolishes or ameliorates most of the isolation-induced
      behavioral and hormonal alterations. Hence, providing isolated animals with brief
      daily periods of social contact may be used as a "preventive treatment" in order
      to protect them from the deleterious effects of isolation.

PMID- 23535243
TI  - Environments predicting intermittent shortening access reduce operant performance
      but not home cage binge size in rats.
AB  - When non-food-deprived rats are given brief access to vegetable shortening (a
      semi-solid fat used in baked products) on an intermittent basis (Monday,
      Wednesday, Friday), they consume significantly more and emit more operant
      responses for shortening than a separate group of rats given brief access to
      shortening every day. Since both groups are traditionally housed in the same
      room, it is possible that the environmental cues associated with placing
      shortening in the cages (e.g., investigator in room, cages opening and closing,
      etc.) provide predictable cues to the daily group, but unpredictable cues to the
      intermittent group. The present study examined the effects of providing
      predictable environmental cues to an isolated intermittent group in order to
      examine the independent contributions of intermittency and predictability on
      intake and operant performance. Two groups of rats were housed in the same room,
      with one group provided 30-min intermittent (INT) access and the second group
      provided 30-min daily access (D) to shortening. A third group (ISO) of rats was
      housed in a room by themselves in which all environmental cues associated with
      intermittent shortening availability were highly predictable. After five weeks of
      home cage shortening access, all rats were then exposed to several different
      operant schedules of reinforcement. The INT and ISO groups consumed significantly
      more shortening in the home cage than the D group. In contrast, the INT group
      earned significantly more reinforcers than both the ISO and D groups under all
      but one of the reinforcement schedules, while ISO and D did not differ. These
      data indicate that intermittent access will generate binge-type eating in the
      home cage independent of cue predictability. However, predictable cues in the
      home cage reduce operant responding independent of intermittent access.

PMID- 23535245
TI  - Coupling between stress coping style and time of emergence from spawning nests in
      salmonid fishes: evidence from selected rainbow trout strains (Oncorhynchus
      mykiss).
AB  - Correlations between behavioral and physiological traits, often referred to as
      stress coping styles, have been demonstrated in numerous animal groups. Such
      trait variations often cluster in two contrasting styles, with animals
      characterized as either proactive or reactive. In natural populations of salmonid
      fishes, emergence from spawning nests, when fry establish a territory and shifts
      from exogenous to endogenous feeding, is a crucial niche shift with a high
      selection pressure. The timing of this event is correlated to behavioral and
      physiological traits such as aggression, boldness/shyness, dominance, and
      metabolic rate; resembling those of proactive and reactive stress coping styles.
      In farmed fish populations, however the relation between emergence and stress
      coping styles seems to be absent, an effect which has been related to lack of
      selection pressure during emergence. In the present study two rainbow trout
      strains genetically selected as LR (low-responsive) and HR (high-responsive)
      trout, characterized with proactive (LR) and reactive (HR) stress coping traits,
      was used to further investigate the relationship between the time of emergence
      and stress coping style in salmonid fishes. For this task LR and HR larvae were
      hatched in mixed batches, and thirty individuals from the earliest and latest 25%
      of emerging larvae were randomly collected. Thereafter, a line specific genetic
      marker was used to distinguish the proportion of LR and HR occurring in early and
      late fractions. The result demonstrates a higher proportion of LR fry in the
      early fraction in comparison to the HR fry, which emerged at a higher proportion
      during the late period. Early emerging individuals had larger yolk reserves at
      emergence, lending further support to a relationship between emergence times,
      yolk reserves at emergence and stress coping styles in salmonids. Smaller larval
      bodies in early compared to late emerging individuals suggest that this
      difference in yolk size reflects differences in developmental stages at
      emergence. These data suggests that a genetic link between emergence time and
      stress coping style persists in captive salmonid fishes.

PMID- 23535246
TI  - The histaminergic H1, H2, and H3 receptors of the lateral septum differentially
      mediate the anxiolytic-like effects of histamine on rats' defensive behaviors in
      the elevated plus maze and novelty-induced suppression of feeding paradigm.
AB  - The neural histaminergic system is involved in a wide range of physiological
      processes, including anxiety. Histaminergic neurons are localized in the
      tuberomammillary nucleus of the posterior hypothalamus and share bidirectional
      connections with the lateral septum, an area well implicated in anxiety. The
      current study examined whether the histaminergic system of the lateral septum
      regulates rats' defensive behaviors in two animal models of anxiety, the elevated
      plus maze (EPM) and novelty-induced suppression of feeding paradigm (NISF). We
      found that bilateral infusions of histamine (1.0 MUg and 5.0 MUg) into the
      lateral septum selectively decreased rats' defensive behaviors in the EPM (both
      doses) and NISF (1.0 MUg only). Follow-up studies found that pre-infusions of the
      H1 and H2 antagonists, pyrilamine (20 MUg) and ranitidine (20 MUg) respectively,
      reversed the anxiolytic-like effects of intra-LS histamine (1.0 MUg) in the NISF
      but not in the EPM, while pre-infusions of the H3 antagonist ciproxifan (200 pg)
      attenuated the anxiolytic-like effects of intra-LS histamine in the EPM but not
      in the NISF. This double dissociation suggests that H1 and H2 receptors in the
      lateral septum, likely via a post-synaptic mechanism, mediate the anxiolytic-like
      effects of histamine in the NISF but not in the EPM. In contrast, lateral septal
      H3 receptors mediate, likely pre-synaptically, the anxiolytic-like effects of
      histamine in the EPM but not in the NISF. Our findings indicate that these
      receptors differentially contribute to rats' specific defensive behaviors in the
      EPM and NISF, that is, avoidance of open spaces and neophagia respectively.

PMID- 23535248
TI  - Risk factors for lymphoma in patients with inflammatory bowel disease: a case
      control study.
AB  - BACKGROUND: Subgroups of patients with inflammatory bowel disease (IBD) may have
      an increased risk of developing lymphoma. We sought to identify factors that were
      associated with lymphoma in patients with IBD. METHODS: Cases and controls were
      identified through a centralized diagnostic index. We identified 80 adult
      patients with IBD who developed lymphoma between 1980 and 2009. For each case, 2
      controls were matched for subtype of IBD, geographic location, and length of
      follow-up. Conditional logistical regression was used to assess associations
      between risk factors and the development of lymphoma. RESULTS: Sixty patients
      were males (75%) versus 77 controls (48%). Median age at index date was 59 years
      for cases and 42 years for controls. Twenty patients (25%) and 23 controls (14%)
      were receiving immunosuppressive medications at the index date. Four patients
      (5%) and 6 controls (4%) were receiving anti-tumor necrosis factor alpha agents
      at the index date. In multiple variable analysis, age per decade (odds ratio,
      1.83; 95% confidence interval, 1.37-2.43), male gender (odds ratio, 4.05; 95%
      confidence interval, 1.82-9.02) and immunosuppressive exposure at the index date
      (odds ratio, 4.20; 95% confidence interval, 1.35-13.11) were significantly
      associated with increased odds of developing lymphoma. Disease severity and use
      of anti-tumor necrosis factor alpha agents were not independently associated with
      developing lymphoma. When testing was performed on patients exposed to
      immunosuppressive or anti-tumor necrosis factor alpha medications, Epstein-Barr
      virus was identified 75% of the time. CONCLUSIONS: In this case-control study,
      increasing age, male gender, and use of immunosuppressive medications were
      associated with an increased risk of lymphoma in patients with IBD.

PMID- 23535247
TI  - Haplotype-tagging analysis of common variants of the IL23R gene demonstrates gene
      wide extent of association with IBD.

PMID- 23535249
TI  - A comparison between anisotropic analytical and multigrid superposition dose
      calculation algorithms in radiotherapy treatment planning.
AB  - Monte Carlo (MC) simulation is currently the most accurate dose calculation
      algorithm in radiotherapy planning but requires relatively long processing time.
      Faster model-based algorithms such as the anisotropic analytical algorithm (AAA)
      by the Eclipse treatment planning system and multigrid superposition (MGS) by the
      XiO treatment planning system are 2 commonly used algorithms. This study compared
      AAA and MGS against MC, as the gold standard, on brain, nasopharynx, lung, and
      prostate cancer patients. Computed tomography of 6 patients of each cancer type
      was used. The same hypothetical treatment plan using the same machine and
      treatment prescription was computed for each case by each planning system using
      their respective dose calculation algorithm. The doses at reference points
      including (1) soft tissues only, (2) bones only, (3) air cavities only, (4) soft
      tissue-bone boundary (Soft/Bone), (5) soft tissue-air boundary (Soft/Air), and
      (6) bone-air boundary (Bone/Air), were measured and compared using the mean
      absolute percentage error (MAPE), which was a function of the percentage dose
      deviations from MC. Besides, the computation time of each treatment plan was
      recorded and compared. The MAPEs of MGS were significantly lower than AAA in all
      types of cancers (p<0.001). With regards to body density combinations, the MAPE
      of AAA ranged from 1.8% (soft tissue) to 4.9% (Bone/Air), whereas that of MGS
      from 1.6% (air cavities) to 2.9% (Soft/Bone). The MAPEs of MGS (2.6%+/-2.1) were
      significantly lower than that of AAA (3.7%+/-2.5) in all tissue density
      combinations (p<0.001). The mean computation time of AAA for all treatment plans
      was significantly lower than that of the MGS (p<0.001). Both AAA and MGS
      algorithms demonstrated dose deviations of less than 4.0% in most clinical cases
      and their performance was better in homogeneous tissues than at tissue
      boundaries. In general, MGS demonstrated relatively smaller dose deviations than
      AAA but required longer computation time.

PMID- 23535250
TI  - Dose absorption in lumbar and femoral dual energy X-ray absorptiometry
      examinations using three different scan modalities: an anthropomorphic phantom
      study.
AB  - The aim of this study was to measure the effective dose on an anthropomorphic
      phantom undergoing lumbar and femoral dual energy X-ray absorption (DXA)
      examinations, using 3 different scan modalities (fast-array [FA], array [A], high
      definition [HD]), and assess the differences in the lifetime attributable risk
      (LAR) of cancer due to radiation. An anthropomorphic phantom was used.
      Thermoluminescent dosimeters were placed over 12 anatomic phantom regions and
      outside the room (to measure background radiation). Fifty scans on the femur and
      spine were performed for each mode. The dose relative to a single DXA scan for
      each dosimeter was measured (mean over the 50 scans) and the background radiation
      was then subtracted. The equivalent dose per organ was obtained. The total body
      effective dose was calculated by adding the equivalent doses. We estimated the
      lifetime dose absorption and LAR for cancer for a male and a female patient
      undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years.
      The effective dose for lumbar scans was FA = 17.79 MUSv, A = 32.88 MUSv, HD =
      31.08 MUSv; for femoral scans, FA = 5.29 MUSv, A = 9.55 MUSv, HD = 7.54 MUSv. LAR
      estimation showed a minimal increase in cancer risk (range 4.55 * 10-4% [FA,
      femoral, male] to 4.02 * 10-3% [A, lumbar, female]). The lifetime dose absorption
      and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18
      lumbar, 18 femoral) every 21 months for 32 years were 0.756 mSv, 3.82 * 10(-3)%
      and 0.756 mSv, 5.11 * 10-3%, respectively. DXA examinations cause radiation
      levels that are comparable to the background radiation. Regardless of the scan
      modality or the anatomic site, a patient undergoing DXA scans for a lifetime has
      a negligible increased risk of developing cancer.

PMID- 23535251
TI  - Development of the microglial phenotype in culture.
AB  - Selected morphological, molecular and functional aspects of various microglial
      cell populations were characterized in cell cultures established from the
      forebrains of E18 rat embryos. The mixed primary cortical cultures were
      maintained for up to 28days using routine culturing techniques when the
      microglial cells in the culture were not stimulated or immunologically
      challenged. During culturing, expansion of the microglial cell populations was
      observed, as evidenced by quantitative assessment of selected
      monocyte/macrophage/microglial cell-specific markers (human leukocyte antigen
      (HLA) DP, DQ, DR, CD11b/c and Iba1) via immunocyto- and histochemistry and
      Western blot analysis. The Iba1 immunoreactivity in Western blots steadily
      increased about 750-fold, and the number of Iba1-immunoreactive cells rose at
      least 67-fold between one day in vitro (DIV1) and DIV28. Morphometric analysis on
      binary (digital) silhouettes of the microglia revealed their evolving morphology
      during culturing. Microglial cells were mainly ameboid in the early stages of in
      vitro differentiation, while mixed populations of ameboid and ramified cell
      morphologies were characteristic of older cultures as the average transformation
      index (TI) increased from 1.96 (DIV1) to 15.17 (DIV28). Multiple
      immunofluorescence labeling of selected biomarkers revealed different microglial
      phenotypes during culturing. For example, while HLA DP, DQ, DR immunoreactivity
      was present exclusively in ameboid microglia (TI<3) between DIV1 and DIV10,
      CD11b/c- and Iba1-positive microglial cells were moderately (TI<13) and
      progressively (TI<81) more ramified, respectively, and always present throughout
      culturing. Regardless of the age of the cultures, proliferating microglia were
      Ki67-positive and characterized by low TI values (TI<3). The microglial function
      was assessed by an in vitro phagocytosis assay. Unstimulated microglia with low
      TI values were significantly more active in phagocytosing fluorescent
      microspheres than the ramified forms. In vitro studies on microglial population
      dynamics combined with phenotypic characterization can be of importance when
      different in vivo pathophysiological situations are modeled in vitro.

PMID- 23535253
TI  - Rearrangement of the dendritic morphology in limbic regions and altered
      exploratory behavior in a rat model of autism spectrum disorder.
AB  - Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat
      epilepsy, bipolar disorders, and migraine; its administration during pregnancy
      increases the risk of autism spectrum disorder (ASD) in the child. Thus, prenatal
      VPA exposure has emerged as a rodent model of ASD. In the present study, we aimed
      to investigate the effect of prenatal administration of VPA (500mg/kg) at E12.5
      on the exploratory behavior and locomotor activity in a novel environment, as
      well as on neuronal morphological rearrangement in the prefrontal cortex (PFC),
      in the hippocampus, in the nucleus accumbens (NAcc), and in the basolateral
      amygdala (BLA) at three different ages: immediately after weaning (postnatal day
      21 [PD21]), prepubertal (PD35) and postpubertal (PD70) ages. Hyper-locomotion was
      observed in a novel environment in VPA animals at PD21 and PD70. Interestingly,
      exploratory behavior assessed by the hole board test at PD70 showed a reduced
      frequency but an increase in the duration of head-dippings in VPA-animals
      compared to vehicle-treated animals. In addition, the latency to the first head
      dip was longer in prenatal VPA-treated animals at PD70. Quantitative
      morphological analysis of dendritic spine density revealed a reduced number of
      spines at PD70 in the PFC, dorsal hippocampus and BLA, with an increase in the
      dendritic spine density in NAcc and ventral hippocampus, in prenatal VPA-treated
      rats. In addition, at PD70 increases in neuronal arborization were observed in
      the NAcc, layer 3 of the PFC, and BLA, with retracted neuronal arborization in
      the ventral and dorsal hippocampus. Our results extend the list of altered
      behaviors (exploratory behavior) detected in this model of ASD, and indicate that
      the VPA behavioral phenotype is accompanied by previously undescribed
      morphological rearrangement in limbic regions.

PMID- 23535252
TI  - Effects of COMT genotype on sensory gating and its modulation by nicotine:
      Differences in low and high P50 suppressors.
AB  - Elevated smoking rates seen in schizophrenia populations may be an attempt to
      correct neuropathologies associated with deficient nicotinic acetylcholine
      receptors and/or dopaminergic systems using exogenous nicotine. However,
      nicotine's effects on cognitive processing and sensory gating have been shown to
      be baseline-dependent. Evidence of a restorative effect on sensory gating
      deficits by nicotine-like agonists has been demonstrated, however, its underlying
      mechanisms in the context of dopamine dysregulation are unclear. Catechol-O
      methyltransferase (COMT), a key dopamine regulator in the brain, contains a co
      dominant allele in which a valine-to-methionine substitution causes variations in
      enzymatic activity leading to reduced synaptic dopamine levels in the Val/Val
      genotype. Using a randomized, double-blind, placebo-controlled design with 57 non
      smokers, this study examined the effects of COMT genotype on sensory gating and
      its modulation by nicotine in low vs. high suppressors. The results were
      consistent with the hypothesis that increased dopamine resulting from nicotine
      stimulation or Met allelic activity would benefit gating in low suppressors and
      impair gating in high suppressors, and that this gating improvement with nicotine
      would be more evident in Val carriers who were low suppressors, while the gating
      impairment would be more evident in Met carriers who were high suppressors. These
      findings reaffirm the importance of baseline-dependency and suggest a subtle
      relationship between COMT genotype and baseline-stratified levels of sensory
      gating, which may help to explain the variability of cognitive abilities in
      schizophrenia populations.

PMID- 23535254
TI  - Terminals of the major thalamic input to visual cortex are devoid of synapsin
      proteins.
AB  - Synapsins are nerve-terminal proteins that are linked to synaptic transmission
      and key factors in several forms of synaptic plasticity. While synapsins are
      generally assumed to be ubiquitous in synaptic terminals, whether they are
      excluded from certain types of terminals is of interest. In the visual pathway,
      synapsins are lacking in photoreceptor and bipolar cell terminals as well as in
      retinogeniculate synapses. These are the terminals of the first three feedforward
      synapses in the visual pathway, implying that lack of synapsins may be a common
      property of terminals that provide the primary driver activity onto their
      postsynaptic neurons. To further investigate this idea, we studied the fourth
      driver synapse, thalamocortical synapses in visual cortex, using glutamatergic
      terminal antibody markers anti-VGluT1 and VGluT2, anti-Synapsin I and II, and
      confocal microscopy to analyze co-localization of these proteins in terminals. We
      also used pre-embedding immunocytochemical labeling followed by electron
      microscopy to investigate morphological similarities or differences between
      terminals containing synapsins or VGluT2. In visual cortex, synapsin coincided
      extensively with non-TC-neuron marker, VGluT1, while thalamocortical terminal
      marker VGluT2 and synapsin overlap was sparse. Morphologically, synapsin-stained
      terminals were smaller than non-stained, while VGluT2-positive thalamocortical
      terminals constituted the largest terminals in cortex. The size discrepancy
      between synapsin- and VGluT2-positive terminals, together with the complementary
      staining patterns, indicates that thalamocortical synapses are devoid of
      synapsins, and support the hypothesis that afferent sensory information is
      consistently transmitted without the involvement of synapsins. Furthermore,
      VGluT2 and synapsins were colocalized in other brain structures, suggesting that
      lack of synapsins is not a property of VGluT2-containing terminals, but a
      property of primary driver terminals in the visual system.

PMID- 23535255
TI  - Long term follow-up of survivors of childhood cancer: summary of updated SIGN
      guidance.

PMID- 23535256
TI  - Recognition, intervention, and management of antisocial behaviour and conduct
      disorders in children and young people: summary of NICE-SCIE guidance.

PMID- 23535257
TI  - Investigating suspected scaphoid fracture.

PMID- 23535258
TI  - Innovate or die.

PMID- 23535259
TI  - Indian plan for rural healthcare providers encounters more resistance.

PMID- 23535260
TI  - Hyperplasia from GLP-1 drugs is "not a surprise," say researchers.

PMID- 23535261
TI  - Government responds to Stafford inquiry with new "whistleblower in chief" to rate
      hospitals.

PMID- 23535262
TI  - Free-standing nanocomposites with high conductivity and extensibility.
AB  - The prospect of electronic circuits that are stretchable and bendable promises
      tantalizing applications such as skin-like electronics, roll-up displays,
      conformable sensors and actuators, and lightweight solar cells. The preparation
      of highly conductive and highly extensible materials remains a challenge for mass
      production applications, such as free-standing films or printable composite inks.
      Here we present a nanocomposite material consisting of carbon nanotubes, ionic
      liquid, silver nanoparticles, and polystyrene-polyisoprene-polystyrene having a
      high electrical conductivity of 3700 S cm(-1) that can be stretched to 288%
      without permanent damage. The material is prepared as a concentrated dispersion
      suitable for simple processing into free-standing films. For the unstrained
      state, the measured thermal conductivity for the electronically conducting
      elastomeric nanoparticle film is relatively high and shows a non-metallic
      temperature dependence consistent with phonon transport, while the temperature
      dependence of electrical resistivity is metallic. We connect an electric fan to a
      DC power supply using the films to demonstrate their utility as an elastomeric
      electronic interconnect. The huge strain sensitivity and the very low temperature
      coefficient of resistivity suggest their applicability as strain sensors,
      including those that operate directly to control motors and other devices.

PMID- 23535263
TI  - Characterization and endocrine regulation of proliferation and differentiation of
      primary cultured preadipocytes from gilthead sea bream (Sparus aurata).
AB  - A preadipocyte primary cell culture was established to gain knowledge about
      adipose tissue development in gilthead sea bream (Sparus aurata), one of the most
      extensively produced marine aquaculture species in the Mediterranean. The
      preadipocytes obtained from the stromal-vascular cell fraction of adipose tissue
      proliferated in culture, reaching confluence around day 8. At that time, the
      addition of an adipogenic medium promoted differentiation of the cells into
      mature adipocytes, which showed an enlarged cytoplasm filled with lipid droplets.
      First, cell proliferation and differentiation were analyzed under control and
      adipogenic conditions during culture development. Next, the effects of insulin,
      GH, and IGF-I on cell proliferation were evaluated at day 8. All peptides
      significantly stimulated proliferation of the cells after 48 h of incubation (P <
      0.002 for GH and IGF-I and P < 0.05 for insulin), despite no differences were
      observed between the different doses tested. Subsequently, the effects of insulin
      and IGF-I maintaining differentiation when added to growth medium were studied at
      day 11, after 3 d of induction with adipogenic medium. The results showed that
      IGF-I is more potent than insulin enhancing differentiation (P < 0.01 for IGF-I
      compared with the control). In summary, a primary culture of gilthead sea bream
      preadipocytes has been characterized and the effects of several regulators of
      growth and development have been evaluated. This cellular system can be a good
      model to study the process of adipogenesis in fish, which may help improve the
      quality of the product in aquaculture.

PMID- 23535264
TI  - Endovascular treatment for aneurysmal subarachnoid hemorrhage in the ninth decade
      of life and beyond.
AB  - OBJECTIVE: As the population ages, clinicians will be faced with difficult
      decisions regarding treatment of elderly patients presenting with aneurysmal
      subarachnoid hemorrhage (aSAH). Previous data have led to continued pessimism by
      some clinicians treating elderly and very elderly patients presenting with aSAH.
      The aim of this study was to present our experience in the very elderly treated
      with endovascular coiling after presentation with aSAH. METHODS: Retrospective
      review of all patients 80 years of age or older presenting with aSAH who
      underwent coil embolization. Primary outcomes of interest were functional
      outcome, as assessed by the Glasgow Outcome Scale score, and inhospital
      mortality. RESULTS: During the study period, 16 patients aged 80 years or older
      presenting with aSAH underwent coil embolization; nine (56%) had a poor outcome
      at the 6 month follow-up while seven (44%) had a good outcome. The inhospital
      mortality rate was 50%. Of those patients alive at discharge, seven out of eight
      (88%) patients had a good outcome. Variables associated with poor outcome
      included higher Hunt and Hess score (p=0.010), use of balloon
      assistance/remodeling (p=0.025), and presence of coronary artery disease
      (p=0.006). CONCLUSIONS: Not surprisingly, we found that very elderly patients
      presenting with aSAH have a high inhospital mortality rate. However, those
      patients who survive to discharge have a surprisingly robust chance at good
      functional recovery when treated with coil embolization. We believe these results
      support offering endovascular coil embolization, when feasible, to very elderly
      patients presenting with aSAH.

PMID- 23535266
TI  - Function of feline signaling lymphocyte activation molecule as a receptor of
      canine distemper virus.
AB  - Morbilliviruses use signaling lymphocyte activation molecule (SLAM) as a receptor
      for their entry to cells. In this study, a complete gene encoding SLAM of a
      domestic cat was identified. The identity of feline SLAM with canine one was 73%,
      and feline SLAM formed the same cluster with those of carnivores. Furthermore,
      feline cell expressing feline SLAM supported growth of canine distemper virus
      (CDV) as well as that expressing canine one. These results indicated that feline
      SLAM can function as a receptor for morbilliviruses, and our established feline
      cells that express feline SLAM might be useful for analysis of morbilliviruses
      originated from felids. 

PMID- 23535265
TI  - CRISPR-Cas systems preferentially target the leading regions of MOBF conjugative
      plasmids.
AB  - Most prokaryotes contain CRISPR-Cas immune systems that provide protection
      against mobile genetic elements. We have focused on the ability of CRISPR-Cas to
      block plasmid conjugation, and analyzed the position of target sequences
      (protospacers) on conjugative plasmids. The analysis reveals that protospacers
      are non-uniformly distributed over plasmid regions in a pattern that is
      determined by the plasmid's mobilization type (MOB). While MOBP plasmids are most
      frequently targeted in the region entering the recipient cell last (lagging
      region), MOBF plasmids are mostly targeted in the region entering the recipient
      cell first (leading region). To explain this protospacer distribution bias, we
      propose two mutually non-exclusive hypotheses: (1) spacers are acquired more
      frequently from either the leading or lagging region depending on the MOB type
      (2) CRISPR-interference is more efficient when spacers target these preferred
      regions. To test the latter hypothesis, we analyzed Type I-E CRISPR-interference
      against MOBF prototype plasmid F in Escherichia coli. Our results show that
      plasmid conjugation is effectively inhibited, but the level of immunity is not
      affected by targeting the plasmid in the leading or lagging region. Moreover,
      CRISPR-immunity levels do not depend on whether the incoming single-stranded
      plasmid DNA, or the DNA strand synthesized in the recipient is targeted. Our
      findings indicate that single-stranded DNA may not be a target for Type I-E
      CRISPR-Cas systems, and suggest that the protospacer distribution bias might be
      due to spacer acquisition preferences. 

PMID- 23535267
TI  - Inactivation of goose parvovirus, avian influenza virus and phage by
      photocatalyst on polyethylen terephthalate film under light emitting diode (LED).
AB  - The inactivation effect of a novel photocatalyst on polyethylene terephthalate
      film on goose parvovirus (GPV), avian influenza virus (AIV) and Qbeta phage was
      evaluated. Under a light emitting diode (LED) light (range 410-750 nm), GPV was
      inactivated by irradiation at 1,000 lux for 6 hr, while AIV and Qbeta phage were
      inactivated by irradiation at 150 lux for 2 hr. These data suggest that this new
      photocatalyst can potentially be used as one of the materials to inactivate
      viruses in the indoor environment and help us to prevent viral infectious
      diseases through indirect contact. 

PMID- 23535268
TI  - Fat graft transfer in children's facial malformations: a prospective three
      dimensional evaluation.
AB  - INTRODUCTION: Autologous fat grafting for volume augmentation in soft tissues has
      grown in popularity in the paediatric plastic surgery community, despite a lack
      of quantifiable evidence of graft survival and predictable outcomes for child
      patients. The objective of this study is to quantify, through an objective
      method, the rate of survival of fat grafting in children's reconstructive
      surgery. METHODS: Clinical evaluation of all children was performed under
      standardised conditions in a prospective fashion with a 1-year follow-up. All
      patients, under 18 years of age, were photographed with a three-dimensional
      imaging system. Data were analysed with three-dimensional analysing software to
      quantify the volume improvements postoperatively and during the follow-up.
      RESULTS: Eleven children were included and followed up for 12 months. The mean
      age was 7.4 years. The mean amount of fat grafted was 13 cm3. At the end of the
      follow-up, the mean survival rate of the fat grafted was 40%. Complementary fat
      grafts were needed in 27% of the cases. No significant complications occurred.
      CONCLUSION: Until now, the literature has failed to provide objective evidence of
      fat survival in children. This study, using three-dimensional data, showed a 40%
      survival of grafted fat. The use of three-dimensional photographs and analysis
      has great clinical potential for surgical planning and follow-up.

PMID- 23535269
TI  - Biotransformation of clerodane diterpenoids by Rhizopus stolonifer and
      antibacterial activity of resulting metabolites.
AB  - Microbial transformation of clerodane lactone (1) by a plant pathogen fungus,
      Rhizopus stolonifer, resulted in the production of metabolites 3 and 4. While
      incubation of clerodane methyl ester (2) by R. stolonifer yielded metabolites 5
      8. The structures of the transformed products were determined by the
      spectroscopic techniques and compounds 4, 7 and 8 were found. The antibacterial
      activity of clerodane diterpenoids 1 and 2 and their metabolites 3-8 were also
      studied. The metabolites 3-7 showed moderate activities against both Gram
      positive and Gram-negative organisms. While metabolite 8 showed a moderate
      activity against Gram-positive organisms and a good activity against Gram
      negative organisms.

PMID- 23535270
TI  - Effects of problem-based learning vs. traditional lecture on Korean nursing
      students' critical thinking, problem-solving, and self-directed learning.
AB  - BACKGROUND: Problem-based learning (PBL) is a method widely used in nursing
      education to develop students' critical thinking skills to solve practice
      problems independently. Although PBL has been used in nursing education in Korea
      for nearly a decade, few studies have examined its effects on Korean nursing
      students' learning outcomes, and few Korean studies have examined relationships
      among these outcomes. OBJECTIVES: The objectives of this study are to examine
      outcome abilities including critical thinking, problem-solving, and self-directed
      learning of nursing students receiving PBL vs. traditional lecture, and to
      examine correlations among these outcome abilities. DESIGN: A quasi-experimental
      non-equivalent group pretest-posttest design was used. PARTICIPANTS/SETTING:
      First-year nursing students (N=90) were recruited from two different junior
      colleges in two cities (GY and GJ) in South Korea. METHODS: In two selected
      educational programs, one used traditional lecture methods, while the other used
      PBL methods. Standardized self-administered questionnaires of critical thinking,
      problem-solving, and self-directed learning abilities were administered before
      and at 16weeks (after instruction). RESULTS: Learning outcomes were significantly
      positively correlated, however outcomes were not statistically different between
      groups. Students in the PBL group improved across all abilities measured, while
      student scores in the traditional lecture group decreased in problem-solving and
      self-directed learning. Critical thinking was positively associated with problem
      solving and self-directed learning (r=.71, and r=.50, respectively, p<.001);
      problem-solving was positively associated with self-directed learning (r=.75,
      p<.001). CONCLUSION: Learning outcomes of PBL were not significantly different
      from traditional lecture in this small underpowered study, despite positive
      trends. Larger studies are recommended to study effects of PBL on critical
      student abilities.

PMID- 23535271
TI  - The PARAMOUNT study and the re-challenge chemotherapy issue in advanced non-small
      cell lung cancer.

PMID- 23535273
TI  - Development of a quantitative biochemical and cellular sphingomyelin synthase
      assay using mass spectrometry.
AB  - The last step in sphingolipid biosynthesis is the conversion of ceramide (Cer) to
      sphingomyelin (SM), which is catalyzed by sphingomyelin synthase (SMS). Two
      isoforms of SMS have been identified with differential subcellular localizations.
      It is not clear whether the two isoforms have any differences in biochemical or
      cellular SMS activities. This report describes a mass spectrometry (MS)-based
      method that was used to characterize biochemical and cellular SMS activities of
      the two isoforms of SMS, namely SMS1 and SMS2. Cellular extracts of SMS1 or SMS2
      expressed in SF9 cells displayed significant SMS activity. When these activities
      were measured by MS, both SMS1 and SMS2 demonstrated similar time- and substrate
      dependent SMS activity. A previously reported SMS inhibitor, D609, inhibited both
      SMS1 and SMS2 activity. In HEK293 cells, overexpression of either SMS1 or SMS2
      significantly increased SMS activity. These studies using MS methods to measure
      SMS activity of SMS1 and SMS2 represent the first quantitative measurement of SMS
      activities. The establishment of quantitative biochemical and cellular SMS assays
      may help to facilitate the discovery of novel SMS1- or SMS2-specific inhibitors.

PMID- 23535272
TI  - crRNA and tracrRNA guide Cas9-mediated DNA interference in Streptococcus
      thermophilus.
AB  - The Cas9-crRNA complex of the Streptococcus thermophilus DGCC7710 CRISPR3-Cas
      system functions as an RNA-guided endonuclease with crRNA-directed target
      sequence recognition and protein-mediated DNA cleavage. We show here that an
      additional RNA molecule, tracrRNA (trans-activating CRISPR RNA), co-purifies with
      the Cas9 protein isolated from the heterologous E. coli strain carrying the S.
      thermophilus DGCC7710 CRISPR3-Cas system. We provide experimental evidence that
      tracrRNA is required for Cas9-mediated DNA interference both in vitro and in
      vivo. We show that Cas9 specifically promotes duplex formation between the
      precursor crRNA (pre-crRNA) transcript and tracrRNA, in vitro. Furthermore, the
      housekeeping RNase III contributes to primary pre-crRNA-tracrRNA duplex cleavage
      for mature crRNA biogenesis. RNase III, however, is not required in the
      processing of a short pre-crRNA transcribed from a minimal CRISPR array
      containing a single spacer. Finally, we show that an in vitro-assembled ternary
      Cas9-crRNA-tracrRNA complex cleaves DNA. This study further specifies the
      molecular basis for crRNA-based re-programming of Cas9 to specifically cleave any
      target DNA sequence for precise genome surgery. The processes for crRNA
      maturation and effector complex assembly established here will contribute to the
      further development of the Cas9 re-programmable system for genome editing
      applications. 

PMID- 23535274
TI  - Enriching pathogen transcripts from infected samples: a capture-based approach to
      enhanced host-pathogen RNA sequencing.
AB  - To fully understand the interactions of a pathogen with its host, it is necessary
      to analyze the RNA transcripts of both the host and pathogen throughout the
      course of an infection. Although this can be accomplished relatively easily on
      the host side, the analysis of pathogen transcripts is complicated by the
      overwhelming amount of host RNA isolated from an infected sample. Even with the
      read depth provided by second-generation sequencing, it is extremely difficult to
      get enough pathogen reads for an effective gene-level analysis. In this study, we
      describe a novel capture-based technique and device that considerably enriches
      for pathogen transcripts from infected samples. This versatile method can, in
      principle, enrich for any pathogen in any infected sample. To test the
      technique's efficacy, we performed time course tissue culture infections using
      Rift Valley fever virus and Francisella tularensis. At each time point, RNA
      sequencing (RNA-Seq) was performed and the results of the treated samples were
      compared with untreated controls. The capture of pathogen transcripts, in all
      cases, led to more than an order of magnitude enrichment of pathogen reads,
      greatly increasing the number of genes hit, the coverage of those genes, and the
      depth at which each transcript was sequenced.

PMID- 23535275
TI  - An analytical solution to the characterization of antigen-antibody interactions
      by kinetic exclusion assay.
AB  - A simpler derivation of the basic expression for the dependence of fluorimetric
      response ratio (R(Ag)/Ro) on free antigen concentration has demonstrated the
      universal invalidity of the analysis that is incorporated into the manufacturer's
      software for determining immunoaffinities by kinetic exclusion assay, and traced
      the error to inadequate allowance for antibody bivalence in the solution phase of
      the assay. An analytical solution to the quantitative characterization of antigen
      antibody interactions from the dependence of R(Ag)/Ro on total antigen
      concentration is also described, thereby eliminating the necessity for the
      extensive simulative procedures employed in current determinations of
      dissociation constants by kinetic exclusion assay. In the illustrative
      application of this analytical approach to published results on the interaction
      between a metal chelate (cadmium-ethylenediaminetetraacetic acid, Cd-EDTA) and an
      elicited monoclonal antibody, the analytical processing of the data has been
      performed on a calculator. However, there is no need to replace the more
      sophisticated procedure that is incorporated into the Sapidyne software provided
      that programming changes are made to rectify the erroneous equation on which the
      simulative analysis is based.

PMID- 23535276
TI  - High-dose prednisone in patients with heart failure and hyperuricemia: friend and
      foe?

PMID- 23535278
TI  - Coffee and caffeine intake and breast cancer risk: an updated dose-response meta
      analysis of 37 published studies.
AB  - OBJECTIVE: We conducted an updated meta-analysis to summarize the evidence from
      published studies regarding the association of coffee and caffeine intake with
      breast cancer risk. METHODS: Pertinent studies were identified by a search of
      PubMed and by reviewing the reference lists of retrieved articles. The fixed or
      random effect model was used based on heterogeneity test. The dose-response
      relationship was assessed by restricted cubic spline model and multivariate
      random-effect meta-regression. RESULTS: 37 published articles, involving 59,018
      breast cancer cases and 966,263 participants, were included in the meta-analysis.
      No significant association was found between breast cancer risk and coffee
      (RR=0.97, P=0.09), decaffeinated coffee (RR=0.98, P=0.55) and caffeine (RR=0.99,
      P=0.73), respectively. And the association was still not significant when
      combining coffee and caffeine (coffee/caffeine) (RR=0.97, P=0.09). However, an
      inverse association of coffee/caffeine with breast cancer risk was found for
      postmenopausal women (RR=0.94, P=0.02), and a strong and significant association
      of coffee with breast cancer risk was found for BRCA1 mutation carriers (RR=0.69,
      P<0.01). A linear dose-response relationship was found for breast cancer risk
      with coffee and caffeine, and the risk of breast cancer decreased by 2% (P=0.05)
      for every 2 cups/day increment in coffee intake, and 1% (P=0.52) for every
      200mg/day increment in caffeine intake, respectively. CONCLUSIONS: Findings from
      this meta-analysis suggested that coffee/caffeine might be weakly associated with
      breast cancer risk for postmenopausal women, and the association for BRCA1
      mutation carriers deserves further investigation.

PMID- 23535277
TI  - CRISPR-mediated defense mechanisms in the hyperthermophilic archaeal genus
      Sulfolobus.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats)-mediated virus
      defense based on small RNAs is a hallmark of archaea and also found in many
      bacteria. Archaeal genomes and, in particular, organisms of the extremely
      thermoacidophilic genus Sulfolobus, carry extensive CRISPR loci each with dozens
      of sequence signatures (spacers) able to mediate targeting and degradation of
      complementary invading nucleic acids. The diversity of CRISPR systems and their
      associated protein complexes indicates an extensive functional breadth and
      versatility of this adaptive immune system. Sulfolobus solfataricus and S.
      islandicus represent two of the best characterized genetic model organisms in the
      archaea not only with respect to the CRISPR system. Here we address and discuss
      in a broader context particularly recent progress made in understanding spacer
      recruitment from foreign DNA, production of small RNAs, in vitro activity of
      CRISPR-associated protein complexes and attack of viruses and plasmids in in vivo
      test systems. 

PMID- 23535279
TI  - Comparative outcomes assessment of uterine grade 3 endometrioid, serous, and
      clear cell carcinomas.
AB  - OBJECTIVE: The objective of this study is to assess effects of clinicopathologic
      risk factors and contemporary therapeutic interventions on high-risk uterine
      epithelial carcinoma outcomes. METHODS: Patient-, disease-, and treatment
      specific variables were annotated. Survival was estimated via the Kaplan-Meier
      method. Associations were evaluated with Cox proportional hazard regression and
      summarized using hazard ratios. RESULTS: From 1999 through 2008, therapy with
      curative intent was initiated for 119 grade 3 endometrioid (G3EC), 211 serous
      (USC), and 40 clear cell (CCC) carcinomas. Although clinicopathologic risk
      factors varied among the histologic subtypes, overall survival (OS) did not
      differ statistically between subtypes (P=.10) or in stage-for-stage comparative
      analyses (stage I/II, P=.45; stage III, P=.46; stage IV, P=.65). The 5-year cause
      specific survival in stage I/II was 84.8%, 89.8%, and 83.9% for G3EC, USC, and
      CCC, respectively; multivariable modeling identified lymphovascular space
      involvement (LVSI) as the only independent prognostic factor (P=.02). For stage
      III, 5-year OS was 49.2% and 40.0% for G3EC and USC, respectively; multivariable
      modeling identified age (P<.001), LVSI (P<.001), unresectable nodal disease
      (P=.03), and regional radiotherapy (P=.01) as independent prognostic factors. For
      stage IV, 5-year OS was 8.7% and 12.1% for G3EC and USC, respectively;
      multivariable modeling identified LVSI (P=.002), cervical stromal invasion
      (P=.02), and adjuvant chemotherapy (P=.02) but not residual disease as
      independent prognostic factors. CONCLUSIONS: When controlled for disease stage,
      outcomes did not differ among high-risk histologic subtypes. LVSI was a
      significant adverse prognostic factor within all stages. The lack of improved
      outcomes with contemporary therapy suggests that more innovative therapeutic
      approaches should be given higher priority.

PMID- 23535280
TI  - Do quiet areas afford greater health-related quality of life than noisy areas?
AB  - People typically choose to live in quiet areas in order to safeguard their health
      and wellbeing. However, the benefits of living in quiet areas are relatively
      understudied compared to the burdens associated with living in noisy areas.
      Additionally, research is increasingly focusing on the relationship between the
      human response to noise and measures of health and wellbeing, complementing
      traditional dose-response approaches, and further elucidating the impact of noise
      and health by incorporating human factors as mediators and moderators. To further
      explore the benefits of living in quiet areas, we compared the results of health
      related quality of life (HRQOL) questionnaire datasets collected from households
      in localities differentiated by their soundscapes and population density: noisy
      city, quiet city, quiet rural, and noisy rural. The dose-response relationships
      between noise annoyance and HRQOL measures indicated an inverse relationship
      between the two. Additionally, quiet areas were found to have higher mean HRQOL
      domain scores than noisy areas. This research further supports the protection of
      quiet locales and ongoing noise abatement in noisy areas.

PMID- 23535281
TI  - Enzyme replacement therapy with galsulfase in 34 children younger than five years
      of age with MPS VI.
AB  - BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and
      multisystem lysosomal storage disease with a wide disease spectrum. Clinical and
      biochemical improvements have been reported for MPS VI patients on enzyme
      replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B;
      galsulfase, Naglazyme(r), BioMarin Pharmaceutical Inc.), making early diagnosis
      and intervention imperative for optimal patient outcomes. Few studies have
      included children younger than five years of age. This report describes 34 MPS VI
      patients that started treatment with galsulfase before five years of age.
      METHODS: Data from patients who initiated treatment at <5 years of age were
      collected from patients' medical records. Baseline and follow-up assessments of
      common symptoms that led to diagnosis and that were used to evaluate disease
      progression and treatment efficacy were evaluated. RESULTS: A significant
      negative correlation was seen with treatment with ERT and urinary GAG levels. Of
      those with baseline and follow-up growth data, 47% remained on their pre
      treatment growth curve or moved to a higher percentile after treatment. Of the 9
      patients with baseline and follow-up sleep studies, 5 remained unaffected and 1
      patient initially with mild sleep apnea showed improvement. Data regarding
      cardiac, ophthalmic, central nervous system, hearing, surgical interventions and
      development are also reported. No patient discontinued treatment due to an
      adverse event and all that were treatment-emergent resolved. CONCLUSIONS: The
      prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and
      effective in slowing and/or improving certain aspects of the disease, although
      patients should be closely monitored for complications associated with the
      natural history of the disease, especially cardiac valve involvement and spinal
      cord compression. A long-term follow-up investigation of this group of children
      will provide further information on the benefits of early treatment as well as
      disease progression and treatment efficacy and safety in this young patient
      population.

PMID- 23535282
TI  - Antireflection properties of graphene layers on planar and textured silicon
      surfaces.
AB  - In this study, theoretical and experimental investigations have been carried out
      to explore the suitability of graphene layers as an antireflection coating.
      Microwave plasma enhanced chemical vapor deposition and chemically grown graphene
      layers deposited on polished and textured silicon surfaces show that graphene
      deposition results in a large decrease in reflectance in the wavelength range of
      300-650 nm, especially in the case of polished silicon. A Si3N4/textured silicon
      reference antireflection coating and graphene deposited polished and textured
      silicon exhibit similar reflectance values, with the graphene/Si surface showing
      lower reflectance in the 300-400 nm range. Comparison of experimental results
      with the finite difference time domain calculations shows that the graphene along
      with a SiO2 surface layer results in a decrease in reflectance in the 300-650 nm
      range, with a reflectance value of <5% for the case of graphene deposited
      textured silicon surfaces. The monolayer and inert character along with the high
      transmittance of graphene make it an ideal surface layer. The results of the
      present study show its suitability as an antireflection coating in solar cell and
      UV detector applications.

PMID- 23535284
TI  - Comparative pooled survival and revision rate of Austin-Moore hip arthroplasty in
      published literature and arthroplasty register data.
AB  - The aim was to evaluate the pooled survival and revision rate of Austin-Moore hip
      arthroplasty (AMHA) in published literature and arthroplasty register data. A
      comprehensive literature analysis of clinical publications and register reports
      was conducted with the main endpoints revision surgery and revision rate. Sixteen
      relevant clinical studies have been found to significantly underestimate revision
      rates by a ratio of 2.15 compared to register data sets. The medium-term outcome
      of AMHA showed significantly worse outcomes than the use of other bipolar
      implants, or modular cervicocephalic prostheses and data of journal publications
      on revision rates deviate significantly from data of arthroplasty registers. 

PMID- 23535283
TI  - Cellular microbiology and molecular ecology of Legionella-amoeba interaction.
AB  - Legionella pneumophila is an aquatic organism that interacts with amoebae and
      ciliated protozoa as the natural hosts, and this interaction plays a central role
      in bacterial ecology and infectivity. Upon transmission to humans, L. pneumophila
      infect and replicate within alveolar macrophages causing pneumonia. Intracellular
      proliferation of L. pneumophila within the two evolutionarily distant hosts is
      facilitated by bacterial exploitation of evolutionarily conserved host processes
      that are targeted by bacterial protein effectors injected into the host cell by
      the Dot/Icm type VIB translocation system. Although cysteine is semi-essential
      for humans and essential for amoeba, it is a metabolically favorable source of
      carbon and energy generation by L. pneumophila. To counteract host limitation of
      cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to
      promote host proteasomal degradation of polyubiquitinated proteins within amoebae
      and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector
      genes have been acquired through inter-kingdom horizontal gene transfer. 

PMID- 23535285
TI  - Functional and radiographic short-term outcome evaluation of the Visionaire
      system, a patient-matched instrumentation system for total knee arthroplasty.
AB  - Patient matched instrumentation is a new operative tool in the field of total
      knee arthroplasty. Custom made cutting blocks are designed to perform distal
      femoral and tibial bone cuts according to a pre-operative planning. This study
      evaluates the Visionaire system of Smith & Nephew. Thirty-one patients, operated
      with the Visionaire technique, were compared to an equal control group for
      different clinical and radiographic outcome parameters. Between both groups, no
      statistical significant difference could be found in post-operative pain,
      satisfaction, functional outcome, hospital stay, blood loss, radiographic
      alignment and precision of bone cuts. Only tibial plateau backslope can be
      created with more precision in the Visionaire group. But there was a statistical
      significant difference for residual flexion deformity after a mean follow-up time
      of 200 days.

PMID- 23535286
TI  - Surgical treatment of trochanteric and cervical hip fractures in the United
      States: 2000-2009.
AB  - The objective of this study was to evaluate the most common treatments performed
      for hip fractures over the last decade in the United States. The leading
      treatment for trochanteric fractures was internal fixation, accounting for 96%
      98% of surgical treatments each year. For cervical fractures, hemiarthroplasty
      (HA), total hip arthroplasty (THA), and internal fixation were performed nearly
      61%, 5%, and 33% of the time, respectively, each year without any sign of change
      during the period assessed. The surgical choice for cervical fractures varied
      greatly by patient age. In 2009, two-thirds of patients younger than 60 years
      underwent internal fixation while two-thirds of patients 60 years or older
      underwent HA. Regardless of patient age, HA was performed more often than THA for
      cervical hip fractures. 

PMID- 23535287
TI  - Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress
      through the Nrf2-dependent antioxidant pathway.
AB  - Cajaninstilbene acid (CSA), an active compound separated from pigeon pea leaves,
      possesses the highly efficient antioxidant activities. Transcription factor
      nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of
      cellular oxidative stress. This study examined the role of Nrf2 in CSA-mediated
      antioxidant effects on human hepatocarcinoma (HepG2) cell line. The generation of
      reactive oxygen species (ROS) upon H2O2 and CSA treatment was lower than that of
      H2O2 alone. CSA activated Nrf2 as evaluated by Western blotting. A luciferase
      reporter assay also demonstrated that CSA-activated signaling resulted in the
      increased transcriptional activity of Nrf2 through binding to the antioxidant
      response element (ARE) enhancer sequence. Our study indicated that treatment of
      HepG2 cells with CSA induces Nrf2-dependent ARE activity and gene expression of
      heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate
      cysteine ligase modifier subunits by activation of PI3K/AKT, ERK and JNK
      signaling pathways. Inhibition of Nrf2 by siRNA reduced CSA-induced upregulation
      of these Nrf2-related enzymes. These results suggest that the Nrf2/ARE pathway
      plays an important role in the regulation of CSA-mediated antioxidant effects in
      HepG2 cells.

PMID- 23535288
TI  - Aberrant activation of M phase proteins by cell proliferation-evoking carcinogens
      after 28-day administration in rats.
AB  - We have previously reported that hepatocarcinogens increase liver cells
      expressing p21(Cip1), a G1 checkpoint protein and M phase proteins after 28-day
      treatment in rats. This study aimed to identify early prediction markers of
      carcinogens available in many target organs after 28-day treatment in rats.
      Immunohistochemical analysis was performed on Ki-67, p21(Cip1) and M phase
      proteins [nuclear Cdc2, phospho-Histone H3 (p-Histone H3), Aurora B and
      heterochromatin protein 1alpha (HP1alpha)] with carcinogens targeting different
      organs. Carcinogens targeting thyroid (sulfadimethoxine; SDM), urinary bladder
      (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole; BHA),
      glandular stomach (catechol; CC), and colon (2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine and chenodeoxycholic acid) were examined using a non-carcinogenic
      toxicant (caprolactam) and carcinogens targeting other organs as negative
      controls. All carcinogens increased Ki-67(+), nuclear Cdc2(+), p-Histone H3(+) or
      Aurora B(+) carcinogenic target cells, except for both colon carcinogens, which
      did not increase cell proliferation. On the other hand, p21(Cip1+) cells
      increased with SDM and CC. HP1alpha responded only to BHA. Results revealed
      carcinogens evoking cell proliferation concurrently induced cell cycle arrest at
      M phase or showing chromosomal instability reflecting aberration in cell cycle
      regulation, irrespective of target organs, after 28-day treatment. Therefore, M
      phase proteins may be early prediction markers of carcinogens evoking cell
      proliferation in many target organs.

PMID- 23535289
TI  - Lives saved by expanding HIV treatment availability in resource-limited settings:
      the example of Haiti.
AB  - BACKGROUND: Guidelines recommend antiretroviral therapy (ART) initiation at CD4
      <350 cells per microliter for HIV-infected individuals in resource-limited
      settings. However, funding for treatment expansion remains uncertain. We forecast
      the mortality impact of ART expansion alternatives in Haiti. METHODS: We used
      data from Haiti to develop a country-specific model of HIV disease. The model
      projects the mortality, total number of HIV-infected individuals, and number and
      coverage (percentage of those eligible) on ART by simulating cohorts of HIV
      infected individuals over 10 years. Five ART expansion scenarios, ranging from
      fully expanded ART (best case) to No New ART (worst case), were assessed.
      RESULTS: By 2010, the model predicts 103,500 individuals living with HIV in
      Haiti, of whom 27,300 were estimated to receive ART. Continuing ART initiation at
      current rates requires increasing the number on ART to 43,300 by 2020 (56%
      coverage), with 89,700 deaths estimated between 2010 and 2020. The number on ART
      could increase by 7400 (+17.1%, best case) or decrease by 25,600 (-59.1%, worst
      case), resulting in 19,500 deaths averted and 9900 fewer in care awaiting ART
      (best versus worst case). Results are sensitive to untreated disease progression
      and pre-ART loss from care. Increased HIV testing, linkage to care, and retention
      in care can avert additional deaths and achieve nearly 80% ART coverage with
      optimal policy improvements. CONCLUSIONS: In resource-limited settings, continued
      improvements in HIV treatment access will save lives. Efforts to efficiently
      expand ART access should remain a global priority.

PMID- 23535290
TI  - Integration of HIV care into primary care in South Africa: effect on survival of
      patients needing antiretroviral treatment.
AB  - BACKGROUND: Integration of HIV care into primary care is a potential strategy to
      improve access to antiretroviral therapy (ART) in high-burden countries. This
      study was conducted to determine the effect of integration of HIV care on the
      survival of patients needing ART. METHODS: A questionnaire was used to measure
      the integration of HIV care into primary care during a randomized controlled
      trial of task shifting and decentralization of HIV care in South Africa. Cox
      proportional hazard ratios (HRs) were estimated for the effect of 5 different
      integration scores (total, pre-ART, ART, mainstreaming HIV, and internal
      integration) on the survival of patients with CD4 count <=350 cells per
      microliter and not yet on ART. RESULTS: A total of 9252 patients were followed up
      for 12-18 months. Cox proportional HRs adjusted for patient and clinic
      characteristics showed decreased risk of mortality in clinics with high scores
      for total integration [HR, 0.97; 95% confidence interval (CI), 0.95 to 0.98; P <
      0.001], ART integration (HR, 0.94; 95% CI, 0.90 to 0.99; P = 0.013), and internal
      integration (HR, 0.97; 95% CI, 0.95 to 1.00; P = 0.041). Analysis of the effect
      of component scores adjusted for patient characteristics only showed decreased
      risk of mortality in clinics with high scores for total integration (HR, 0.97;
      95% CI, 0.94 to 1.00; P = 0.032), pre-ART integration (HR, 0.92; 95% CI, 0.85 to
      0.99; P = 0.027), ART integration (HR, 0.95; 95% CI, 0.93 to 0.98; P = 0.001),
      and mainstreaming HIV (HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.007). CONCLUSION: In
      a context of task shifting and decentralization of care, integration of HIV care
      into primary care is associated with improved survival of HIV-positive patients
      needing ART.

PMID- 23535291
TI  - Association between ALT level and the rate of cardio/cerebrovascular events in
      HIV-positive individuals: the D: A: D study.
AB  - BACKGROUND: An inverse association between serum alanine aminotransferase (ALT)
      levels and the risk of myocardial infarction (MI) has been reported in the
      general population. We investigated associations between ALT levels and the risk
      of various cardiovascular and cerebrovascular outcomes in a large cohort study of
      HIV-positive individuals. METHODS: Using Poisson regression, we investigated
      associations between the latest ALT level and MI, coronary heart disease (CHD),
      and stroke, after adjusting for known confounders and cumulative/recent exposure
      to antiretroviral drugs. Analyses were also performed for the end points of all
      cause/liver-related mortality and new-onset diabetes mellitus. RESULTS: By
      February 2011, participants had experienced 541 MIs, 804 CHD, and 258 stroke
      events. The MI rate decreased from 3.1/1000 person-years among those with ALT
      <=18 U/L to 2.1/1000 person-years among those with ALT >60 U/L. After adjustment
      for confounders, each 2-fold increment in ALT was associated with a 19% drop in
      the MI rate {relative rate, 0.81 [95% confidence interval (CI): 0.74 to 0.89], P
      = 0.0001}. A weaker inverse association was seen for CHD with no indication of a
      linear association between ALT levels and stroke (P = 0.72). Adjusted relative
      rates were 0.88 (95% CI: 0.81 to 0.97) and 0.70 (95% CI: 0.54 to 0.92) in those
      who were hepatitis C virus negative and hepatitis C virus positive, respectively,
      and 0.72 (95% CI: 0.58 to 0.89) and 0.84 (0.77 to 0.93) in injection drug users
      and non-injection drug users, respectively. Liver-related mortality and diabetes
      both demonstrated a positive association with ALT levels, whereas all-cause
      mortality showed a U-shaped relationship. CONCLUSIONS: Higher ALT levels are
      associated with lower MI risk in HIV-positive individuals, but with higher risks
      of liver-related mortality and diabetes mellitus.

PMID- 23535292
TI  - Influence of low-dose ritonavir with and without darunavir on the
      pharmacokinetics and pharmacodynamics of inhaled beclomethasone.
AB  - OBJECTIVE: To identify an alternative inhaled corticosteroid to fluticasone
      propionate that can be safely coadministered with HIV protease inhibitors, the
      safety and pharmacokinetics of beclomethasone dipropionate (BDP) and its active
      metabolite, beclomethasone 17-monopropionate (17-BMP), in combination with
      ritonavir (RTV) and darunavir/ritonavir (DRV/r) were assessed. DESIGN: Open
      label, prospective, randomized pharmacokinetic and pharmacodynamic study in
      healthy volunteers. METHODS: Thirty healthy volunteers received inhaled 160 MUg
      bid BDP for 14 days and were then randomized (1:1:1) into 3 groups: group 1
      (control) remained on BDP alone for 28 days, group 2 received 100 mg bid BDP +
      RTV for 28 days, and group 3 received 600/100 mg bid BDP + DRV/r for 28 days.
      Pharmacokinetic sampling for 17-BMP was performed on days 14 and 28, and
      pharmacokinetic parameter values were compared within patients and between
      groups. Cortisol stimulation testing was also performed on days 1, 14, 28, and 42
      and compared within and between groups. RESULTS: Geometric mean ratios (day
      28:day 14) (90% confidence interval) for 17-BMP area under the concentration-time
      curve in groups 1, 2, and 3, respectively, were 0.93 (0.81 to 1.06, P = 0.27),
      2.08 (1.52 to 2.65, P = 0.006), and 0.89 (0.68 to 1.09, P = 0.61). There were no
      significant reductions in serum cortisol levels within or between groups (P >
      0.05). CONCLUSIONS: DRV/r did not increase 17-BMP exposure, whereas RTV alone
      produced a statistically significant but clinically inconsequential 2-fold
      increase in 17-BMP exposure. Adrenal suppression was not observed in any of the
      study groups. These data suggest that BDP can be safely coadministered with DRV/r
      and likely other RTV-boosted protease inhibitors.

PMID- 23535293
TI  - Behavioral, biological, and demographic risk and protective factors for new HIV
      infections among youth in Rakai, Uganda.
AB  - BACKGROUND: Prevalence of HIV infection is considerable among youth, although
      data on risk factors for new (incident) infections are limited. We examined
      incidence of HIV infection and risk and protective factors among youth in rural
      Uganda, including the role of gender and social transitions. METHODS:
      Participants were sexually experienced youth (15-24 years old) enrolled in the
      Rakai Community Cohort Study, 1999-2008 (n = 6741). Poisson regression with
      robust standard errors was used to estimate incident rate ratios (IRR) and 95%
      confidence intervals (CI) of incident HIV infection. RESULTS: HIV incidence was
      greater among young women than young men (14.1 vs. 8.3 per 1000 person-years,
      respectively); this gender disparity was greater among teenagers (14.9 vs. 3.6).
      Beyond behavioral (multiple partners and concurrency) and biological factors
      (sexually transmitted infection symptoms), social transitions such as marriage
      and staying in school influenced HIV risk. In multivariate analyses among women,
      HIV incidence was associated with living in a trading village (adjusted IRR
      (aIRR) = 1.48; 95% CI: 1.04 to 2.11), being a student (aIRR = 0.22; 95% CI: 0.07
      to 0.72), current marriage (aIRR = 0.55; 95% CI: 0.37 to 0.81), former marriage
      (aIRR = 1.73; 95% CI: 1.01 to 2.96), having multiple partners, and sexually
      transmitted infection symptoms. Among men, new infections were associated with
      former marriage (aIRR = 5.57; 95% CI: 2.51 to 12.36), genital ulceration (aIRR =
      3.56; 95% CI: 1.97 to 6.41), and alcohol use (aIRR = 2.08; 95% CI: 1.15 to 3.77).
      CONCLUSIONS: During the third decade of the HIV epidemic in Uganda, HIV incidence
      remains considerable among youth, with young women particularly at risk. The risk
      for new infections was strongly shaped by social transitions such as leaving
      school, entrance into marriage, and marital dissolution; the impact of marriage
      was different for young men than women.

PMID- 23535294
TI  - Reduction in perinatal HIV infections in KwaZulu-Natal, South Africa, in the era
      of more effective prevention of mother to child transmission interventions (2004
      2012).
AB  - OBJECTIVE: To describe a trend in perinatal HIV transmission associated with the
      implementation of rapidly changing prevention of mother to child transmission
      (PMTCT) interventions from 2004 to 2012. METHOD: Retrospective analysis of infant
      HIV polymerase chain reaction results of infants from 2004 to 2012 archived from
      a Laboratory Information System. SETTING: KwaZulu-Natal, South Africa. MAIN
      OUTCOME MEASURE: HIV infection in infants aged 4-8 weeks. RESULTS: The proportion
      of 4- to 8-week-old infants who tested HIV polymerase chain reaction positive
      decreased significantly (P < 0.0001) from 27.5% in 2004 to 2.9% in 2012. The
      reduction rates in perinatal HIV infections in 4- to 8-week-old HIV-exposed
      infants decreased significantly (P < 0.0001) by 48.7% following single-dose
      nevirapine (sdNVP) (2005 to April 2008), 68.4% with zidovudine from 28 weeks and
      sdNVP together with triple antiretroviral therapy for women with CD4 cell count <
      200 cells/mm3 (May 2008-April 2010), and 89.5% with zidovudine from 14 weeks,
      sdNVP, and triple antiretroviral therapy for women with CD4+ cell count < 350
      cells/mm3 (May 2010-December 2012). CONCLUSIONS: We show an almost 10-fold
      reduction in mother to child transmission from 2004 to 2012 in infants aged 4-8
      weeks during a rapid implementation of more complex and robust PMTCT
      interventions. The significant reductions in mother to child transmission in the
      South African PMTCT program are encouraging for a middle-income country with the
      second highest antenatal HIV prevalence in the world.

PMID- 23535295
TI  - Achievement and maintenance of viral suppression in persons newly diagnosed with
      HIV, New York City, 2006-2009: using population surveillance data to measure the
      treatment part of "test and treat".
AB  - BACKGROUND: Viral suppression reduces HIV-related morbidity and transmission to
      uninfected partners. Models suggest that the transmission benefit may extend to
      whole communities. METHODS: We used New York City surveillance data to analyze
      viral suppression among persons newly diagnosed with HIV between 2006 and 2009.
      The Kaplan-Meier product limit method was used to estimate the cumulative
      proportion achieving suppression and experiencing failure. Cox proportional
      hazards regression was used to identify factors associated with time to achieve
      suppression and duration of suppression and to calculate hazard ratios (HRs).
      RESULTS: Among the 12,122 new diagnoses, 7663 (63.2%) ever achieved suppression
      by June 30, 2011, 26.6% within 6 months and 39.8% within 12 months of diagnosis.
      89.2% of those ever achieving suppression maintained it for 6 months, and 81.9%
      for 12 months. The proportion achieving and maintaining suppression improved with
      each successive diagnostic year (P < 0.0001). Patients with initial CD4 <350
      cells per cubic millimeter achieved suppression more rapidly (P < 0.0001) and
      maintained it longer. Those with the highest nadir CD4 before suppression (>=500
      cells/mm3) were least likely to maintain it (men: HR = 0.72; 95% confidence
      interval, 0.61 to 0.82 and women: HR = 0.67; 95% confidence interval, 0.53 to
      0.87). CONCLUSIONS: Persons in successively later diagnostic cohorts and those
      with nadir CD4 at the federal antiretroviral therapy threshold had larger
      proportions suppressed, faster time to suppression, and longer duration. New
      guidelines recommending therapy independent of CD4 may result in improvements in
      proportion suppressed in future diagnostic cohorts.

PMID- 23535296
TI  - Comparable performance of conventional and liquid-based cytology in diagnosing
      anal intraepithelial neoplasia in HIV-infected and -uninfected Thai men who have
      sex with men.
AB  - BACKGROUND: Anal cytology has increasingly been used to screen for anal
      intraepithelial neoplasia (AIN) among men who have sex with men (MSM) at
      increased risk for anal cancer. Use of liquid-based cytology has been reported to
      reduce fecal and bacterial contamination and air-drying artifact compared with
      conventional cytology. Costs associated with liquid-based cytology, however, may
      limit its use in resource-limited settings. METHODS: Anal swab samples were
      collected from MSM participants and used to prepare conventional and liquid-based
      cytology slides. Abnormal conventional cytology results triggered referral for
      high-resolution anoscopy and biopsy. Agreement between the 2 cytology techniques
      and the positive predictive value ratios of histology confirmed AIN were
      calculated. RESULTS: Among 173 MSM, abnormal anal cytology was identified in
      46.2% of conventional and 32.4% of liquid-based slides. The results agreed in
      62.4% of cases with a kappa value of 0.49 (P < 0.001). HIV-infected MSM had a 3.6
      fold increased odds of having discordant anal cytology results (95% confidence
      interval: 1.6 to 7.8; P = 0.001) compared with HIV-uninfected MSM. Histological
      AIN 2 and 3 were identified in 20 MSM. The positive predictive value ratios and
      95% confidence interval indicated no difference between the 2 techniques.
      CONCLUSIONS: Conventional anal cytology may be a preferred option for resource
      limited settings given comparable performances to liquid-based cytology for the
      detection of AIN, although the agreement between the 2 techniques was lower among
      HIV-infected MSM. Due to high prevalence of abnormal anal cytology and AIN,
      health systems should prepare adequate infrastructure for high-resolution
      anoscopy services and AIN treatment.

PMID- 23535297
TI  - Rap2b, a novel p53 target, regulates p53-mediated pro-survival function.
AB  - The tumor suppressor p53 is a critical regulator of apoptosis and cell cycle
      arrest/pro-survival. Upon DNA damage, p53 evokes both cell cycle arrest/pro
      survival and apoptosis transcriptional programs. The ultimate cellular outcome
      depends on the balance of these two programs. However, the p53 downstream targets
      that mediate this cell fate decision remain to be identified. Using an
      integrative genomic approach, we identify Rap2b as a conserved p53-activated gene
      that counters p53-mediated apoptosis after DNA damage. Upon DNA damage, p53
      directly binds to the promoter of Rap2b and activates its transcription. The
      reduction of Rap2b levels by small interference RNA sensitizes cells to DNA
      damage-induced apoptosis in a p53-dependent manner. Consistent with its pro
      survival function, analysis of cancer genomic data reveals that Rap2b is
      overexpressed in many types of tumors. Anchorage-independent growth assays show
      that Rap2b has only weak transformation activity, suggesting that it is not an
      oncogene by itself. Together, our results identify Rap2b as a new player in the
      pro-survival program conducted by p53 and raise the possibility that targeting
      Rap2b could sensitize tumor cells to apoptosis in response to DNA damage.

PMID- 23535298
TI  - UNC119a bridges the transmission of Fyn signals to Rab11, leading to the
      completion of cytokinesis.
AB  - Src family kinases (SFKs) regulate the completion of cytokinesis through signal
      transduction pathways that lead to the Rab11-dependent phosphorylation of ERK and
      its localization to the midbody of cytokinetic cells. We find that UNC119a, a
      known activator of SFKs, plays essential roles in this signaling pathway. UNC119a
      localizes to the centrosome in interphase cells and begins to translocate from
      the spindle pole to the spindle midzone after the onset of mitosis; it then
      localizes to the intercellular bridge in telophase cells and to the midbody in
      cytokinetic cells. We show that the midbody localization of UNC119a is dependent
      on Rab11, and that knocking down UNC119a inhibits the Rab11-dependent
      phosphorylation and midbody localization of ERK and cytokinesis. Moreover, we
      demonstrate that UNC119a interacts with a Src family kinase, Fyn and is required
      for the activation of this kinase. These results suggest that UNC119a plays a key
      role in the Fyn signal transduction pathway, which regulates the completion of
      cytokinesis via Rab11.

PMID- 23535299
TI  - Molecular and phylogenetic analysis of influenza A H1N1 pandemic viruses in Cuba,
      May 2009 to August 2010.
AB  - The influenza A(H1N1)pdm09 virus was detected in Cuba in May 2009. The
      introduction of a new virus with increased transmissibility into a population
      makes surveillance of the pandemic strain to the molecular level necessary. The
      aim of the present study was the molecular and phylogenetic analysis of pandemic
      influenza A(H1N1)pdm09 strains that circulated in Cuba between May 2009 and
      August 2010. Seventy clinical samples were included in the study. Nucleotide
      sequences from the hemagglutinin HA1 region segment were obtained directly from
      clinical samples. Genetic distances were calculated using MEGA v.5.05. A
      phylogenetic tree was constructed using MrBayes v.3.1.2 software. Potential N
      glycosylation sites were predicted using NetNGlyc server 1.0. The 48 Cuban
      sequences of influenza A(H1N1)pdm09 obtained were similar to the
      A/California/07/2009 (H1N1) vaccine strain. Most of the Cuban strains belonged to
      clade 7. Cuban viruses showed amino acid changes, some of them located at three
      antigenic sites: Ca, Sa, and Sb. Two dominant mutations were detected: P83S
      (100%) and S203T (85.7%). Glycosylation site analysis revealed the gain of one
      site at position 162 in 13 sequences. The findings in this study contribute to
      our understanding of the progress of the influenza A(H1N1)pdm09 virus, since this
      virus is at the starting point of its evolution in humans.

PMID- 23535300
TI  - Candidemia among adults in Soweto, South Africa, 1990-2007.
AB  - BACKGROUND: Studies on candidemia occurring among adults in Southern African are
      limited. We aimed to document the epidemiology of candidemia among adults in
      Soweto. METHODS: This was a retrospective hospital-based study in three discrete
      periods, involving 9 years, from 1990 to 2007. RESULTS: Two hundred and sixty-six
      patients were identified. Case rates were 2.8 cases/10 000 admissions in 1998
      2002 and 3.6 episodes/10 000 hospitalizations in 2005-2007. In 1990, Candida
      albicans caused 62% and Candida tropicalis caused 23% of episodes. In 2005-2007,
      major species were C. albicans (46%), Candida parapsilosis (25%), and Candida
      glabrata (23%), with little change compared to 1998-2002. Major predisposing
      conditions were abdominal surgery (43%), HIV infection (19% in 2005-2007), trauma
      (16%), diabetes mellitus (12%), and cancer (8%). General wards superseded
      intensive care as the major diagnostic setting in 2005-2007. The crude mortality
      was 60%. Among 22 HIV-infected patients with a median CD4 cell count of 68/MUl,
      three were of community-onset. C. albicans caused 73% of cases. Five patients had
      another predisposing condition and five had central venous catheters. The
      mortality was 73%. CONCLUSIONS: Soweto has a pattern of Candida species different
      from other continents. HIV infection and trauma were important predisposing
      conditions.

PMID- 23535301
TI  - A simple diagnostic aid for tuberculous meningitis in adults in Morocco by use of
      clinical and laboratory features.
AB  - BACKGROUND: The delay in diagnosis and treatment of tuberculous meningitis (TBM)
      is a major factor in the high mortality observed with this pathology. The
      distinction between bacterial meningitis (BM) and TBM by clinical features alone
      is often impossible, and the available biological resources remain inadequate or
      inaccessible, especially in developing countries. We attempted to develop a
      simple diagnostic algorithm on the basis of clinical and laboratory findings that
      could be used as an early predictor of TBM in adult patients in Morocco. METHODS:
      We compared the clinical and laboratory features on admission of 508 adults in a
      medical intensive care unit in Morocco who satisfied diagnostic criteria for
      tuberculous (n=274) or bacterial (n=234) meningitis. Features independently
      predictive of TBM were modeled by multivariate logistic regression to create a
      diagnostic rule, and by a classification and regression tree (CART). RESULTS: Six
      features were predictive of a diagnosis of TBM: female gender, duration of
      symptoms, the presence of localizing signs, white blood cell (WBC) count, the
      level of serum sodium, and the total cerebrospinal fluid WBC count. The
      sensitivity for CART was 87% and for a score >7 was 88%; specificity was 96% and
      95%, respectively. The internal validation was excellent for both diagnostic
      methods, with a receiver operating characteristic (ROC) area of 0.906 bootstrap
      samples for a score >7 and 0.910 for CART. CONCLUSIONS: The clinical and
      laboratory parameters identified in this study may help the clinician with the
      empiric diagnosis of TBM and could be used in settings with limited
      microbiological diagnostic support.

PMID- 23535302
TI  - Clinical efficacy and predictors of outcomes of repeat hepatectomy for recurrent
      hepatocellular carcinoma - a systematic review.
AB  - BACKGROUND: Primary hepatectomy is an accepted treatment for primary
      hepatocellular carcinoma (HCC) with good long-term survival, but high rates of
      recurrence. This review aims to evaluate the safety and efficacy of repeat
      hepatectomy for recurrent HCC after initial hepatectomy. METHODS: Electronic
      searches identified 22 eligible studies comprising of 1125 patients for
      systematic review. Studies with >10 patients, adopting repeat hepatectomy
      treatment for recurrent HCC initially treated with hepatectomy were selected for
      inclusion. A predetermined set of data comprising demographic details, morbidity
      and mortality indices and survival outcomes were collected for every study and
      tabulated. RESULTS: Majority of patients selected for repeat hepatectomy had
      Child-Pugh A (median 94%, range 40-100). Intrahepatic recurrence occurred at a
      median of 22.4 (range 12-48) months in this patient cohort with single nodule
      recurrences comprising of 70% of cases. The median mortality rate was 0% (range 0
      6%). Prolonged ascites was observed in a median of 4% (range 0-32%), bleeding in
      1% (range 0-9%), bile leak in 1% (range 0-6%) and liver failure in 1% (range 0
      2%). The median disease-free survival was 15 (range 7-32) months and median
      overall survival was 52 (range 22-66) months. Median 3-year and 5-year survival
      was 69% (range 41-88%) and 52% (range 22-83%) respectively. Recurrences occurring
      12-18 months after initial hepatectomy was consistently associated with improved
      survival. CONCLUSION: Synthesized data from observational studies of repeat
      hepatectomy suggests that this treatment approach for recurrent HCC is safe and
      achieves long-term survival. Standardization of criteria for repeat hepatectomy
      and a randomized trial are warranted.

PMID- 23535303
TI  - Incidence and mortality trends for four major cancers in the elderly and middle
      aged adults: an international comparison.
AB  - BACKGROUND: Time trends comparisons by age are important to understand the
      specific needs of elderly cancer patients and to improve clinical procedures. The
      aim is to compare 1998-2005 cancer incidence and mortality trends in Italy and
      the US for both sexes and for two age groups, namely 50-69 year old and 70+ year
      old. METHODS: Cancer incidence and mortality data came from 22 Cancer Registries
      (CRs) of the Italian association of cancer registries (AIRTUM), while the US
      incidence records were provided by 13 SEER CRs and the mortality statistics
      provided by the WHO Database. Trends were analysed by the Joinpoint Regression
      Program in order to obtain Annual Percent Changes and Joinpoints. RESULTS:
      Colorectal cancer incidence trends were favourable in the US for both sexes and
      in both age groups, whilst the rates increased in Italian elderly individuals and
      mortality rates fell markedly only in the US. For lung cancer, incidence and
      mortality decreased in men but increased in women in the two geographical areas.
      Breast cancer incidence and mortality declined both in Italy and the US for
      younger women, but the trends were less favourable in the Italian elderly
      individuals. The increase of prostate incidence slowed down and mortality
      diminished for every age group in the US, whilst in Italy only in the younger
      group. CONCLUSIONS: For major cancers, the Italian elderly experienced less
      favourable trends than the middle-aged patients whereas, in the US, the trends
      were similar for both age groups and favourable also for the elderly.

PMID- 23535304
TI  - Enzymatic interesterification of a lard and rapeseed oil equal-weight blend.
AB  - A mixture of lard and rapeseed oil (1:1, wt/wt) was interesterified using
      immobilized lipases from Rhizomucor miehei (Lipozyme RM IM) and Candida
      antarctica (Novozym 435) as catalysts. Enzymatic interesterifications were
      carried out at 60 degrees C for 8 h with Lipozyme RM IM or at 80 degrees C for 4
      h with Novozym 435. The biocatalyst doses were kept constant (8 wt-%). The
      starting blend was quantitatively separated by column chromatography into pure
      triacylglycerol fraction (98.5%), and a nontriacylglycerol fraction containing
      free fatty acids (0.3%) and of mono- and diacylglycerols (1.2%). It was found
      that after interesterification the contents of free fatty acids and of mono- and
      diacylglycerols increased to 3.5% and 6.3% or to 1.5% and 4.5% when Lipozyme RM
      IM and Novozym 435 were used, respectively.The slip melting temperatures and
      solid fat contents of the triacylglycerol fractions separated from
      interesterified samples were lower compared with the nonesterified blend. The sn
      2 and sn-1,3 distribution of fatty acids in the triacylglycerol fractions before
      and after interesterification were determined. The compositions of fatty acids at
      sn-2 were near statistical (33.3%) when Novozym 435 was used. When Lipozyme RM IM
      was used, the fatty acid compositions at the sn-2 position remained practically
      unchanged, compared with the starting blend. The changes in molecular structures
      of fat components due to interesterification have greatly influenced on the
      melting profiles of products as illustrated by the DSC melting scans. The
      interesterified fats and isolated triacylglycerols had reduced oxidative
      stabilities, as assessed by Dynamic DSC and Isothermal PDSC measurements. The
      Arrhenius kinetic parameters for fats oxidation based on DSC and PDSC
      measurements were calculated.

PMID- 23535305
TI  - Distillation time effect on lavender essential oil yield and composition.
AB  - Lavender (Lavandula angustifolia Mill.) is one of the most widely grown essential
      oil crops in the world. Commercial extraction of lavender oil is done using steam
      distillation. The objective of this study was to evaluate the effect of the
      length of the distillation time (DT) on lavender essential oil yield and
      composition when extracted from dried flowers. Therefore, the following
      distillation times (DT) were tested in this experiment: 1.5 min, 3 min, 3.75 min,
      7.5 min, 15 min, 30 min, 60 min, 90 min, 120 min, 150 min, 180 min, and 240 min.
      The essential oil yield (range 0.5-6.8%) reached a maximum at 60 min DT. The
      concentrations of cineole (range 6.4-35%) and fenchol (range 1.7-2.9%) were
      highest at the 1.5 min DT and decreased with increasing length of the DT. The
      concentration of camphor (range 6.6-9.2%) reached a maximum at 7.5-15 min DT,
      while the concentration of linalool acetate (range 15-38%) reached a maximum at
      30 min DT. Results suggest that lavender essential oil yield may not increase
      after 60 min DT. The change in essential oil yield, and the concentrations of
      cineole, fenchol and linalool acetate as DT changes were modeled very well by the
      asymptotic nonlinear regression model. DT may be used to modify the chemical
      profile of lavender oil and to obtain oils with differential chemical profiles
      from the same lavender flowers. DT must be taken into consideration when citing
      or comparing reports on lavender essential oil yield and composition.

PMID- 23535306
TI  - High fat and high cholesterol diet induces DPP-IV activity in intestinal lymph.
AB  - Recent studies have reported that dipeptidyl-peptitase IV (DPP-IV) is correlated
      with diabetic conditions and also with dyslipidemia caused by overnutrition,
      especially a high fat diet. However, the role of DPP-IV in diabetes during
      dyslipidemia has been unclear. We utilized a lymph fistula rat model to determine
      whether intestinal lymph, which absorbs dietary fats, is affected by a chronic
      high-fat and high-cholesterol diet (HFHC). HFHC diet rats showed significantly
      higher DPP-IV activity in intestinal lymph and plasma compared to rats receiving
      a normal chow diet. In addition, HFHC diet rats showed significantly increased
      DPP-IV mRNA expression in the intestine. However, DPP-IV mRNA in the lymphocytes
      isolated from intestinal lymph and mesenteric lymph nodes did not show
      significant differences from that in the normal diet rats. In conclusion, HFHC
      diets increased DPP-IV expression in intestinal lymph; these results indicate the
      applicability of a previously unrecognized role for DPP-IV in metabolic
      disorders, including diabetes.

PMID- 23535307
TI  - Oxidized trilinoleate and tridocosahexaenoate induce pica behavior and change
      locomotor activity.
AB  - Pica behavior, a behavior that is characterized by eating a nonfood material such
      as kaolin and relates to the degree of discomfort in animals, and the variations
      of locomotor activity of rats after eating deteriorated fat and oil extracted
      from instant noodles were examined in our previous study. The result shows that
      oxidized fat and oil with at least 100 meq/kg in peroxide value (PV) increase
      pica behavior and decrease locomotor activity. In the present study, the same two
      behaviors were measured using autoxidized trilinoleate (tri-LA) and
      tridocosahexaenoate (tri-DHA) as a model of vegetable and fish oil, respectively,
      to compare fatty acid differences against the induction of two behaviors. The
      oxidized levels of tri-LA and tri-DHA were analyzed with PV and p-anisidine value
      (AnV), the method to analyze secondary oxidized products. The oxidation levels of
      respective triacylglycerol (TAG) samples were carefully adjusted to make them
      having almost the same PV and AnV. As the results, 600 or more meq/kg in PV of
      both TAGs significantly increased the consumption of kaolin pellets compared to
      the control group. Furthermore, 300 or more meq/kg in PV of tri-LA and 200 or
      more meq/kg in PV of tri-DHA demonstrated significant decrease in locomotor
      activity compared to control group. These results would indicate that the
      oxidized TAG having the same PV and/or AnV would induce the same type of pica
      behavior and locomotor activity. Furthermore, that the structure of oxidized
      products might not be important and the amount of hydroperoxide group and/or
      aldehyde group in deteriorated fats and oils might affect the pica behavior and
      locomotor activity were thought.

PMID- 23535308
TI  - Solution properties of tadpole-type cationic amphiphilic dendrimers consisting of
      an alkyl chain, a quaternary ammonium, and a poly(amidoamine) dendron.
AB  - Tadpole-type amphiphilic dendrimers consisting of an alkyl chain, a quaternary
      ammonium bromide (qb) and a poly(amidoamine) dendron (den) (CnqbdenGm, where n
      represents an alkyl chain with a length of 10,14, or 18 carbons; m is the
      generation number G of dendron taking the value -0.5, 0.5, or 1.5) were
      synthesized using N, N-dimethylethylenediamine as a central scaffold. Electrical
      conductivity, surface tension, pyrene fluorescence, and dynamic light scattering
      measurements were used to characterize the properties of the dendrimers. In
      addition, the effect of the alkyl chain length and the generation number of a
      dendron on these properties was evaluated through a comparison with those of the
      corresponding previously reported amphiphilic dendrimers with lactobionamide
      sugar terminal groups (CnqbdenGmLac) and conventional cationic monomeric
      surfactants (CnTAB). Both critical micelle concentration (cmc) and surface
      tension (except for C18 series) were lower than those of CnqbdenGmLac and CnTAB
      with the same alkyl chain length, indicating that the synthesized amphiphilic
      dendrimers have an excellent micelle-forming ability in solution and high
      adsorption ability at the air/water interface, in spite of the large bulky
      dendron structure. When the alkyl chain length and the generation number of the
      amphiphilic dendrimers were increased, the surface tension became high because of
      the curved long alkyl chain and the bulky structure of dendron. Further,
      CnqbdenGm formed micelles with a small size in solution, and the micelles of
      CnqbdenG(-0.5) had almost a constant size despite the changes in the
      concentration, while those of CnqbdenG0.5 and CnqbdenG1.5 became smaller with
      increasing concentration. The difference in the behavior results from the
      difference in the number of amide groups in the low- and high-generation
      dendrons.

PMID- 23535309
TI  - Derivation of quantitative removal efficiency of protein stain from K/S value of
      washing test fabric soiled with hemoglobin.
AB  - We have improved a previous method for the preparation of hemoglobin-soiled
      fabrics in order to facilitate quantitative calculation of the efficiency with
      which protein stains can be removed from such materials. We then evaluated the
      sensitivity of surface reflectance as a method for stain quantification. Test
      fabrics were made by spotting a white fabric with a certain amount of hemoglobin
      solution and drying it. We observed a large difference between the percentage
      stain removal as measured by surface reflectance when compared with chemical
      analysis. Deformities in the surface of the soiled fabric caused by capillary
      action in the drying process likely contributed to this difference. Quantitative
      removal percentage could be predicted easily from the K/S values of test fabrics
      that were dry-heated without steam, although soil adhesion was too weak to
      evaluate the washing power of commercial detergent. Overall, we found that
      practical test fabrics with adequate soil adhesion properties can be prepared by
      adopting a steam heating process after dry heating.

PMID- 23535310
TI  - Highly selective and asymmetric reductive biotransformation of alpha-ionone by
      Epicoccum purpurascens.
AB  - The biotransformation of terpenoid C13 norisoprenoid (+/-)-alpha-ionone (1) using
      the plant pathogenic fungus Epicoccum purpurascens as a biocatalyst was
      investigated for the production of useful novel organic compounds. There are no
      reported biotransformations using E. purpurascens. The biotransformation of
      compound 1 via reduction of the C-9 ketone position yielded alpha-ionol (2) as
      the major metabolic product. Reduction of the racemic alpha-ionone [(-)-(6S)- and
      (+)-(6R)-] resulted in the exclusive formation of the two enantiomers (-)-(6S,9R)
      and (+)-(6R,9S)-alpha-ionol (2). Thus, the enzymatic reduction of alpha-ionone
      by E. purpurascens proceeds with high asymmetry.

PMID- 23535311
TI  - Antioxidant activities and phenolics of Passiflora edulis seed recovered from
      juice production residue.
AB  - Passion fruit seed was refluxed in methanolic water and further liquid - liquid
      extracted yielding n-Hexane, Ethyl acetate (EtOAc) and aqueous (Aq.) extracts.
      The EtOAc part was the most potent antioxidant (IC 50DPPH = 2.7 +/- 0.2 and IC
      50ABTS = 9.0 +/- 0.0 ug/mL) that significantly (p < 0.05) better than Aq. extract
      (IC 50DPPH = 177.8 +/- 1.3 and IC 50ABTS = 15.4 +/- 0.0 ug/mL). The antioxidant
      EtOAc exhibited ferric reducing powder (EC1mM FeSO4 = 2,813.9 +/- 11.6) and
      tyrosinase inhibitory effect (39.9 +/- 0.0 % at 1 mg/mL). The more potent active
      extract had significant higher total phenolic content than the Aq. one (p <
      0.05). Sun protection factor of the EtOAc extract was comparable to ferulic acid.
      Chlorogenic acid, rosmarinic acid and quercetin were highly found in EtOAc
      extract, whereas kojic acid and gallic acid were largely determined in the Aq.
      part. The most potent biologically active fraction was non cytotoxic in vero
      cells at the highest test concentration (50 ug/mL). A process to minimize the
      waste from the fruit juice production is offered. Passion fruit value and
      profitability in agribusinesses will be increased by the biochemical
      transformation of the seed into active extracts appraisal for natural cosmetic as
      a multifunction ingredient.

PMID- 23535312
TI  - Application of activated carbons from coal and coconut shell for removing free
      residual chlorine.
AB  - This study investigated the removal of free residual chlorine by activated carbon
      (AC). ACs were prepared from coal (AC1) and coconut shell (AC2). The specific
      surface area of AC1 was larger than that of AC2. The removal of free residual
      chlorine increased with elapsed time and amount of adsorbent. The removal
      mechanism of free residual chlorine was the dechlorination reaction between
      hypochlorous acid or hypochlorite ion and AC. Moreover, AC1 was useful in the
      removal of free residual chlorine in tap water. The optimum condition for the
      removal of free residual chlorine using a column is space velocity 306 1/h; liner
      velocity 6.1 m/h.

PMID- 23535313
TI  - Influence of imperfect reference standard bias on the diagnostic performance of
      MRI in the detection of lymphomatous bone marrow involvement.

PMID- 23535314
TI  - Re: a pooled analysis of MRI in the detection of bone marrow infiltration in
      patients with malignant lymphoma. A reply.

PMID- 23535315
TI  - Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis
      of CT findings and their prognostic value.
AB  - AIM: To investigate the computed tomography (CT) findings in patients with stage
      IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal
      cavity and to evaluate whether imaging findings revealed by CT have prognostic
      value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with
      IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging
      findings were investigated, and evaluated imaging findings were analysed for the
      prognostic value of overall survival (OS) and disease-free survival (DFS).
      RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative,
      38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all
      imaging findings, local invasiveness (n = 26, 42%), including bony destruction,
      erosion, or soft-tissue involvement, was the only independent prognostic factor
      for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42
      10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis
      of 36 cases with no local invasiveness, a superficial infiltrative pattern in one
      nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p =
      0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions
      for treatment outcomes. Local invasiveness revealed by CT findings was a strong
      prognostic factor for poor OS and DFS. In addition, in patients with no local
      invasiveness, a superficial infiltrative pattern in one nasal cavity predicted
      favourable OS and DFS.

PMID- 23535316
TI  - Determination of urinary stone composition using dual-energy spectral CT: initial
      in vitro analysis.
AB  - AIM: To evaluate the feasibility of determining the chemical composition of
      urinary stones using computed tomography (CT) spectral imaging (SI) MATERIALS AND
      METHODS: Two hundred and ten urinary stones were scanned in vitro using the SI
      mode and conventional polychromatic imaging (CPI; 120 kVp) mode. The radiodensity
      at 50 keV and 120 kVp, the mean calcium density (CD), and the water density (WD)
      were measured using the 50 keV images, 120 kVp images, calcium-based images, and
      water-based images, respectively. These parameters and the calcium-water ratio
      (CWR) were compared between different types of stones. CWR was defined as: CWR =
      ?calcium density/water density?. RESULTS: According to the results determined by
      infrared spectroscopy, 116 pure urinary stones were divided into five groups:
      uric acid (UA, n = 16), struvite (STR, n = 23), cystine (CYS, n = 10), calcium
      phosphate (CaP, n = 29), and calcium oxalate (COX, n = 38). CD, CWR, and the
      radiodensity of stones at 50 keV CT imaging of each group were as follows: UA (
      3.55 +/- 10.85 mg/ml, 0.03 +/- 0.05, 510.08 +/- 157.29 HU); STR (224.99 +/- 64.28
      mg/ml, 0.19 +/- 0.07, 1058.58 +/- 260.13 HU); CYS (139.67 +/- 34.66 mg/ml, 0.13
      +/- 0.03, 725.75 +/- 142.35 HU); CaP (619.39 +/- 26.13 mg/ml, 0.69 +/- 0.11,
      2617.46 +/- 186.22 HU); COX (518.61 +/- 95.5 mg/ml, 0.58 +/- 0.1, 2247.47 +/-
      379.51 HU). The differences in the CD, CRW, and radiodensity of stones at 50 keV
      CT imaging among the groups were statistically significant by binary comparison
      (p < 0.05). There were no significant differences in the radiodensity of stones
      at 120 keV CT imaging between UA and CYS (p = 0.267), CaP and COX (p = 0.065),
      and in the WD between STR and CYS (p = 0.108). CONCLUSION: SI provides a novel
      method to better characterize pure urinary stones using the mean CD, CWR, and the
      radiodensity of stones at 50 keV CT imaging.

PMID- 23535317
TI  - Characterization and quantification of the influence of season and gender on
      plasma chemistries of Hermann's tortoises (Testudo hermanni, Gmelin 1789).
AB  - The present study is the first to monitor plasma chemistries of a group of 30
      Hermann's tortoises (HTs) over two summer seasons to characterize and quantify
      seasonal and gender-related influences. The following analytes were analyzed:
      ALT, ALP, AST, BA, CA, CHO, CK, LDH, GLU, GLDH, P, TP, TRIG, urea and uric acid.
      Two-way repeated-measures ANOVA, mean values, confidence intervals were
      calculated. The overall results showed distinct patterns and somewhat unexpected
      results concerning the plasma chemistry changes induced by season and gender in a
      majority of routine biochemical analytes. TRIG, CHO, CA, and P were significantly
      higher in females. AST, ALT, BA, LDH and GLDH showed an increase in males in
      midsummer. ALP showed a significant and analogous seasonal variation for both
      sexes. GLU showed a moderate increase during midsummer. Uric acid and urea
      concentrations showed a distinct seasonal variation. For some analytes, fitted
      curves could be calculated describing the seasonal variation.

PMID- 23535318
TI  - Innovation in the collection of food availability data: a case study of the
      Chicago Department of Public Health Sanitarian Survey.

PMID- 23535319
TI  - The anchoring protein SAP97 influences the trafficking and localisation of
      multiple membrane channels.
AB  - SAP97 is a member of the MAGUK family of proteins that play a major role in the
      trafficking and targeting of membrane ion channels and cytosolic structural
      proteins in multiple cell types. Within neurons, SAP97 is localised throughout
      the secretory trafficking pathway and at the postsynaptic density (PSD). SAP97
      differs from other MAGUK family members largely in its long N-terminus and in the
      sequences between the SH3 and GUK domains, where SAP97 undergoes significant
      alternative splicing to produce multiple SAP97 isoforms. These splice insertions
      endow SAP97 with differential cellular localisation patterns and functional roles
      within neurons. With regard to membrane ion channels, SAP97 forms multi-protein
      complexes with AMPA and NMDA-type glutamate receptors, and Kv1.4, Kv4.2, and
      Kir2.2 potassium channels, playing a major role in trafficking and anchoring ion
      channel surface expression. This highlights SAP97 not only as a regulator of
      neuronal excitability, synaptic function and plasticity in the brain, but also as
      a target for the pathophysiology of a number of neurological disorders. This
      article is part of a Special Issue entitled: Reciprocal influences between cell
      cytoskeleton and membrane channels, receptors and transporters. Guest Editor:
      Jean Claude Herve. 

PMID- 23535320
TI  - Potent naphthoquinones against antimony-sensitive and -resistant Leishmania
      parasites: synthesis of novel alpha- and nor-alpha-lapachone-based 1,2,3
      triazoles by copper-catalyzed azide-alkyne cycloaddition.
AB  - Continuing our screening program for novel anti-parasite compounds, we
      synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-beta
      lapachone-based 1,2,3-triazoles and ten alpha-lapachone-based 1,2,3-triazoles.
      These and other naphthoquinonoid compounds were evaluated for their activity
      against promastigote forms of antimony-sensitive and -resistant strains of
      Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The
      toxicity of these compounds to mammalian cells was also examined. The substances
      were more potent than an antimonial drug, with IC50 values ranging from 1.0 to
      50.7 MUM. Nor-alpha-lapachone derivatives showed the highest antileishmanial
      activity, with selectivity indices in the range of 10-15. These compounds emerged
      as important leads for further investigation as antileishmanial agents.
      Additionally, one of these compounds exhibited cross-resistance in Sb-resistant
      Leishmania and could provide a molecular tool for investigating the multidrug
      resistance mechanisms in Leishmania parasites.

PMID- 23535321
TI  - Heterocyclic bismuth carboxylates based on a diphenyl sulfone scaffold: synthesis
      and antifungal activity against Saccharomyces cerevisiae.
AB  - A series of heterocyclic organobismuth(III) carboxylates 4 and 5 [RCO2Bi(C6H4-2
      SO2C6H4-1'-)] derived from diphenyl sulfone was synthesized to determine the
      influence of the carboxylate ligand structure on the lipophilicity and antifungal
      activity against the yeast Saccharomyces cerevisiae. In contrast to the clear
      structure-activity relationship between the size of the inhibition zone and the
      value of ClogP for specific substitution on diphenyl sulfone scaffold 1 [ClBi(5
      RC6H3-2-SO2C6H4-1'-)], scaffolds 4 and 5 showed similar inhibition activities
      irrespective of the ClogP value. This suggests that these molecules function
      inside the yeast cell by separating into the cationic heterocyclic bismuth
      scaffold and the anionic carboxylate moiety, and that the bismuth scaffold plays
      an important role in the inhibition activity.

PMID- 23535322
TI  - Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as
      anti-cancer agents.
AB  - A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained
      via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of
      compounds 9a-j was evaluated against human leukemia cell lines (K562 and CEM).
      The compounds exhibited moderate to good anti-cancer activity with compounds 9b
      and 9i having a chloro group exhibiting the best activity (IC50 = 10 MUM).
      Compound 9i exhibited activity against both the cell lines and 9b only exhibited
      activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA
      fragmentation studies of the compounds 9a-j were also performed.

PMID- 23535323
TI  - Repeated use of subcutaneous levetiracetam in a palliative care patient.

PMID- 23535324
TI  - Hope in newly diagnosed cancer patients.
AB  - CONTEXT: Hope is important to cancer patients as it helps them deal with their
      diagnosis. Little is known about hope in newly diagnosed cancer patients.
      OBJECTIVES: Based on the Transcending Possibilities conceptual model of hope, the
      purpose of this study was to examine the relationship of hope with pain, energy,
      and psychological and demographic characteristics in newly diagnosed adult
      oncology outpatients. METHODS: Data from 310 New Patient Assessment Forms from
      cancer outpatients' health records were collected. Health records from the first
      six months of 2009 were reviewed and data were collected on hope, energy, pain,
      depression, anxiety, feeling overwhelmed, and demographic variables. A
      generalized linear modeling approach was used to study the relationship of hope
      scores with these variables. Hypothesized variables and variables that were
      significant at the P = 0.01 level from the univariate analysis were entered into
      the multivariate model, with hope scores as the dependent variable. RESULTS: Hope
      scores were significantly negatively related to age (P = 0.02). More
      specifically, oncology patients who were 65 years of age or older had
      significantly less hope than those under the age of 65 years (P = 0.01). Gender
      (P = 0.009) also was a significant factor, with men having higher hope scores
      than women. No other variables were significant. CONCLUSION: Older adults
      comprise the majority of persons in Canada with cancer. The lower hope scores
      found in this age group compared with their younger counterparts underscore the
      importance of further research. This study provides a foundation for future
      research in this important area for oncology patients.

PMID- 23535325
TI  - Living with advanced but stable multiple myeloma: a study of the symptom burden
      and cumulative effects of disease and intensive (hematopoietic stem cell
      transplant-based) treatment on health-related quality of life.
AB  - CONTEXT: The cumulative impact of disease and treatment-related factors on health
      related quality of life (HRQoL) in long-term survivors of multiple myeloma is
      poorly characterized. OBJECTIVES: To characterize HRQoL and symptom burden in
      advanced, intensively treated myeloma. METHODS: We performed detailed assessments
      in patients who had undergone hematopoietic stem cell transplantation and
      subsequent treatment for at least one episode of progressive disease. To exclude
      the impact of active disease and acute toxicity of treatment, patients were in a
      stable plateau phase. Patients were assessed for HRQoL (Short Form-12, European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 30, and Multiple Myeloma Module), pain (Brief Pain Inventory-Short Form),
      peripheral neuropathy (self-report Leeds Assessment of Neuropathic Symptoms and
      Signs), and concerns (adapted from Profile of Concerns). Serum interleukin-6 and
      tumor necrosis factor-alpha were measured. RESULTS: A total of 32 patients were
      enrolled, with a median age of 55 years at diagnosis and 60 years at assessment.
      After a median 5.5 years from diagnosis and three lines of treatment, physical
      functioning was significantly compromised (P<0.001) and associated with
      progressive work disability and concerns regarding loss of independence. Fatigue
      and pain were the predominant symptoms, impacting negatively on physical
      functioning (P<0.001). Pain was predominantly neuropathic in half the patients.
      Serum interleukin-6 levels positively correlated with pain (P=0.03), pain
      interference (P=0.003), insomnia (P=0.02), and appetite loss (P=0.02), and
      inversely correlated with physical functioning (P=0.03). CONCLUSION: Despite
      disease control and supportive care, intensively treated long-term myeloma
      survivors have significantly compromised HRQoL related to symptom burden.
      Systematic assessment is routinely indicated in advanced phase myeloma, even when
      disease activity is stable. Further studies should investigate the utility of
      interventional strategies and the relationship of cytokines with symptoms.

PMID- 23535326
TI  - Novel and highly potent histamine H3 receptor ligands. Part 3: an alcohol
      function to improve the pharmacokinetic profile.
AB  - Synthesis and biological evaluation of potent histamine H3 receptor antagonists
      incorporating a hydroxyl function are described. Compounds in this series
      exhibited nanomolar binding affinities for human receptor, illustrating a new
      possible component for the H3 pharmacophore. As demonstrated with compound
      BP1.4160 (cyclohexanol 19), the introduction of an alcohol function counter
      intuitively allowed to reach high in vivo efficiency and favorable
      pharmacokinetic profile with reduced half-life.

PMID- 23535327
TI  - Synthesis and structure-activity relationship of pyripyropene A derivatives as
      potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors:
      part 2.
AB  - Synthesis and structure-activity relationships of 7-O-p-cyanobenzoyl pyripyropene
      A derivatives with modification at C1 and 11 are described. Regioselective mono
      deprotection of di-tert-butylsilylene acetal was critical in their synthesis.

PMID- 23535328
TI  - Discovery, synthesis, selectivity modulation and DMPK characterization of 5
      azaspiro[2.4]heptanes as potent orexin receptor antagonists.
AB  - Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted
      piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin
      2 receptor antagonist class has been discovered. SAR and Pharmacokinetic
      optimization of this series is herein disclosed. Lead compound 15 exhibits potent
      activity against orexin 1 and orexin 2 receptors along with low cytochrome P450
      inhibition potential, good brain penetration and oral bioavailability in rats.

PMID- 23535329
TI  - Enantiocomplementary access to carba-analogs of C-nucleoside derivatives by
      recombinant Baeyer-Villiger monooxygenases.
AB  - A novel and stereoselective synthetic route towards carba-C-nucleosides was
      investigated applying an enantiodivergent biooxidation strategy by two different
      Baeyer-Villiger monooxygenases. Within only three chemo-enzymatic steps it was
      possible to introduce four chiral centers starting from commercially available
      non-chiral starting material.

PMID- 23535330
TI  - Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new
      class of CHK1 inhibitors.
AB  - Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1
      inhibitors have uncovered specific combinations of key substructures within the
      molecule; resulting in significant improvements in cell-based activity while
      retaining a greater than one hundred-fold selectivity against CDK2. The X-ray
      crystal structure of a complex between compound 39 and the CHK1 protein detailing
      a 'U-shaped' topology and key interactions with the protein surface at the ATP
      site is also reported.

PMID- 23535331
TI  - Healthcare neglects effects of smoking among mentally ill people, says report.

PMID- 23535332
TI  - Beneficial effects of the RESMENA dietary pattern on oxidative stress in patients
      suffering from metabolic syndrome with hyperglycemia are associated to dietary
      TAC and fruit consumption.
AB  - Hyperglycemia and oxidative stress are conditions directly related to the
      metabolic syndrome (MetS), whose prevalence is increasing worldwide. This study
      aimed to evaluate the effectiveness of a new weight-loss dietary pattern on
      improving the oxidative stress status on patients suffering MetS with
      hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie
      diets (-30% Energy): the control diet based on the American Health Association
      criteria and the RESMENA diet based on a different macronutrient distribution
      (30% proteins, 30% lipids, 40% carbohydrates), which was characterized by an
      increase of the meal frequency (seven-times/day), low glycemic load, high
      antioxidant capacity (TAC) and high n-3 fatty acids content. Dietary records,
      anthropometrical measurements, biochemical parameters and oxidative stress
      biomarkers were analyzed before and after the six-month-long study. The RESMENA
      (Metabolic Syndrome Reduction in Navarra) diet specifically reduced the android
      fat mass and demonstrated more effectiveness on improving general oxidative
      stress through a greater decrease of oxidized LDL (oxLDL) values and protection
      against arylesterase depletion. Interestingly, oxLDL values were associated with
      dietary TAC and fruit consumption and with changes on body mass index (BMI),
      waist circumference, fat mass and triacilglyceride (TG) levels. In conclusion,
      the antioxidant properties of the RESMENA diet provide further benefits to those
      attributable to weight loss on patients suffering Mets with hyperglycemia.

PMID- 23535333
TI  - MICAL, the flavoenzyme participating in cytoskeleton dynamics.
AB  - MICAL (from the Molecule Interacting with CasL) indicates a family of recently
      discovered cytosolic, multidomain proteins, which uniquely couple an N-terminal
      FAD-containing monooxygenase-like domain to typical calponine homology, LIM and
      coiled-coil protein-interaction modules. Genetic and cell biology approaches have
      demonstrated an essential role of the catalytic activity of the monooxygenase
      like domain in transducing the signal initiated by semaphorins interaction with
      their plexin receptors, which results in local actin cytoskeleton disassembly as
      part of fundamental processes that include differentiation, migration and cell
      cell contacts in neuronal and non-neuronal cell types. This review focuses on the
      structure-function relations of the MICAL monooxygenase-like domain as they are
      emerging from the available in vitro studies on mouse, human and Drosophila MICAL
      forms that demonstrated a NADPH-dependent actin depolymerizing activity of MICAL.
      With Drosophila MICAL forms, actin depolymerization was demonstrated to be
      associated to conversion of Met44 to methionine sulfone through a postulated
      hydroxylating reaction. Arguments supporting the concept that MICAL effect on F
      actin may be reversible will be discussed.

PMID- 23535334
TI  - Impact of cell wall composition on maize resistance to pests and diseases.
AB  - In cereals, the primary cell wall is built of a skeleton of cellulosic
      microfibrils embedded in a matrix of hemicelluloses and smaller amounts of
      pectins, glycoproteins and hydroxycinnamates. Later, during secondary wall
      development, p-coumaryl, coniferyl and sinapyl alcohols are copolymerized to form
      mixed lignins. Several of these cell wall components show a determinative role in
      maize resistance to pest and diseases. However, defense mechanisms are very
      complex and vary among the same plant species, different tissues or even the same
      tissue at different developmental stages. Thus, it is important to highlight that
      the role of the cell wall components needs to be tested in diverse genotypes and
      specific tissues where the feeding or attacking by the pathogen takes place.
      Understanding the role of cell wall constituents as defense mechanisms may allow
      modifications of crops to withstand pests and diseases.

PMID- 23535336
TI  - Trends in nanopharmaceutical patents.
AB  - Investment in nanotechnology is now a given constant by governments, research
      centers and companies in both more developed countries and emerging markets. Due
      to their characteristics, such as high stability, ability to enable antigen
      identification on specific cells in the human body and controlling the release of
      drugs and, therefore, improving therapies, nanoparticles have been the subject of
      research and patent applications in the pharmaceutical field. According to the
      Organization for Economic Co-operation and Development (OCDE), patent data can be
      used as a source of information in order to measure science and technology
      activities. Thereby, this paper presents an analysis based on patent documents
      related to nanotechnology in the pharmaceutical sector. As a result, the analysis
      of patents demonstrate primarily that nanobiotechnology attracts high levels of
      R&D investments, including nanoparticle-based chemotherapeutic agents/drugs,
      monoclonal antibody nanoparticle complexes and their role in drug delivery or
      contrast agents with non-toxic effects.

PMID- 23535337
TI  - Disruption of AtWNK8 enhances tolerance of Arabidopsis to salt and osmotic
      stresses via modulating proline content and activities of catalase and
      peroxidase.
AB  - With no lysine kinases (WNKs) play important roles in plant growth and
      development. However, its role in salt and osmotic stress tolerance is unclear.
      Here, we report that AtWNK8 is mainly expressed in primary root, hypocotyl,
      stamen and pistil and is induced by NaCl and sorbitol treatment. Compared to the
      wild-type, the T-DNA knock-out wnk8 mutant was more tolerant to severe salinity
      and osmotic stresses, as indicated by 27% and 198% more fresh weight in the NaCl
      and sorbitol treatment, respectively. The wnk8 mutant also accumulated 1.43-fold
      more proline than the wild-type in the sorbitol treatment. Under NaCl and
      sorbitol stresses, catalase (CAT) activity in wnk8 mutant was 1.92- and 3.7-times
      of that in Col-0, respectively. Similarly, under salt and osmotic stress
      conditions, peroxidase (POD) activities in wnk8 mutant were 1.81- and 1.58-times
      of that in Col-0, respectively. Taken together, we revealed that maintaining
      higher CAT and POD activities might be one of the reasons that the disruption of
      AtWNK8 enhances the tolerance to salt stress, and accumulating more proline and
      higher activities of CAT and POD might result in the higher tolerance of WNK8 to
      osmotic stress.

PMID- 23535335
TI  - Melatonin and pancreatic islets: interrelationships between melatonin, insulin
      and glucagon.
AB  - The pineal hormone melatonin exerts its influence in the periphery through
      activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms
      are expressed in the islet of Langerhans and are involved in the modulation of
      insulin secretion from beta-cells and in glucagon secretion from alpha-cells. De
      synchrony of receptor signaling may lead to the development of type 2 diabetes.
      This notion has recently been supported by genome-wide association studies
      identifying particularly the MT2 as a risk factor for this rapidly spreading
      metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion,
      it is safe to assume that it also has a diurnal impact on the blood-glucose
      regulating function of the islet. This factor has hitherto been underestimated;
      the disruption of diurnal signaling within the islet may be one of the most
      important mechanisms leading to metabolic disturbances. The study of melatonin
      insulin interactions in diabetic rat models has revealed an inverse relationship:
      an increase in melatonin levels leads to a down-regulation of insulin secretion
      and vice versa. Elucidation of the possible inverse interrelationship in man may
      open new avenues in the therapy of diabetes.

PMID- 23535338
TI  - Lipid status of the two high latitude fish species, Leptoclinus maculatus and
      Lumpenus fabricii.
AB  - A comparative study of the lipid status (i.e., the total lipid and phospholipid
      concentrations and the percentage of fatty acids of the total lipids) of adult
      specimens of daubed shanny (Leptoclinus maculatus) from Svalbard waters (Isfjord)
      and slender eel blenny (Lumpenus fabricii) from the White Sea (Onega Bay and
      Tersky shore) was performed to study the metabolism and functions of lipids of
      these fishes in ontogeny and under various ecological conditions. Slender eel
      blenny from both areas of the White Sea were distinguished by a high level of
      sphingomyelin compared with the daubed shanny from Svalbard, and the amount of
      total phospholipids was higher in slender eel blenny from Onega Bay than in
      slender eel blenny from the Tersky shore. The extent of saturation and the
      signature of polyenic fatty acids varied according to the specific species of the
      Stichaeidae family under study. These results demonstrate the differences in the
      trophoecological and hydrobiological conditions of habitations of these species
      and highlighted the importance of considering certain trends in the lipid
      profiles of these fishes as specific features of the organization of the
      ecological and biochemical mechanisms of adaptation.

PMID- 23535340
TI  - A year-long caregiver training program to improve neurocognition in preschool
      Ugandan HIV-exposed children.
AB  - OBJECTIVE: Mediational intervention for sensitizing caregivers (MISC) is a
      structured program enabling caregivers to enhance their child's cognitive and
      emotional development through daily interactions. The principal aim was to
      evaluate if a year-long MISC caregiver training program produced greater
      improvement in child cognitive and emotional development compared with a control
      program. METHODS: One hundred and nineteen uninfected HIV-exposed preschool
      children and their caregivers were randomly assigned to 1 of 2 treatment arms:
      biweekly MISC training alternating between home and clinic for 1 year or a health
      and nutrition curriculum. All children were evaluated at baseline, 6 months, and
      1 year with the Mullen Early Learning Scales, Color-Object Association Test for
      memory, and Achenbach Child Behavior Checklist for psychiatric symptoms.
      Caregivers were evaluated on the same schedule with the Hopkins Symptoms
      Checklist-25 for depression and anxiety. RESULTS: The treatment arms were
      compared using repeated-measures analysis of covariance with child age, gender,
      weight, socioeconomic status, caregiving quality, caregiver anxiety, and
      caregiver education as covariates. The MISC children had significantly greater
      gains compared to controls on the Mullen Receptive and Expressive Language
      development, and on the Mullen composite score of cognitive ability. Color-Object
      Association Test total memory for MISC children was marginally better than
      controls. No Achenbach Child Behavior Checklist differences between the groups
      were noted. Caldwell Home Observation for Measurement of the Environment scores
      and observed mediational interaction scores from videotapes measuring caregiving
      quality also improved significantly more for the MISC group. CONCLUSIONS: The
      MISC enhanced cognitive performance, especially in language development. These
      benefits were possibly mediated by improved caregiving and positive emotional
      benefit to the caregiver.

PMID- 23535341
TI  - Ostracism in pediatric populations: review of theory and research.
AB  - Ostracism, ignoring and excluding a target individual, has recently emerged as
      one of the more common and damaging forms of social exchange. This article
      reviews the theoretical and empirical foundations of ostracism and its impact on
      the targeted individual, especially threats to the fundamental psychological
      needs of belonging, self-esteem, meaningful existence, and sense of control.
      Ostracism in children and adolescents is under-researched compared to bullying in
      general, in both the general youth population and in populations of children and
      youth with special health care needs (CYSHCN). Basic and applied studies on
      ostracism and its impact are reviewed with special emphasis on recent findings
      about ostracism in CYSHCN. Evidence is presented that ostracism may pose an even
      greater threat to children's adjustment and need-threat levels than bullying.
      Resources for clinician and researcher engagement in this emerging area are
      provided.

PMID- 23535342
TI  - A multi-component nanocomposite screen-printed ink with non-linear touch
      sensitive electrical conductivity.
AB  - Printable electronics is an innovative area of technology with great commercial
      potential. Here, a screen-printed functional ink, comprising a combination of
      semiconducting acicular particles, electrically insulating nanoparticles and a
      base polymer ink, is described that exhibits pronounced pressure sensitive
      electrical properties for applications in sensing and touch sensitive surfaces.
      The combination of these components in the as-printed ink yield a complex
      structure and a large and reproducible touch pressure sensitive resistance range.
      In contrast to the case for some composite systems, the resistance changes occur
      down to applied pressures of 13 Pa. Current-voltage measurements at fixed
      pressures show monotonic non-linear behaviour, which becomes more Ohmic at higher
      pressures and in all cases shows some hysteresis. The physical basis for
      conduction, particularly in the low pressure regime, can be described in terms of
      field assisted quantum mechanical tunnelling.

PMID- 23535343
TI  - Nanostructured poly(L-lactide) matrix as novel platform for drug delivery.
AB  - With the aim to establish new strategies for fabricating bioactive nanostructured
      matrices for controlled drug delivery or potential tissue engineering, a facile
      and one-pot protocol was developed in this study to produce drug-loaded poly(l
      lactide) (PLLA) nanostructures by thermally induced phase separation. Using both
      steroidal and nonsteroidal anti-inflammatory drugs, we demonstrated that
      lipophilic drugs can be efficiently incorporated in either nanosheet-like or
      nanofibrous PLLA matrices. Thus entrapped drug was randomly distributed in the
      interconnected nanostructures in the form of nanoscaled crystals. In vitro
      release study revealed that drug release kinetics may be modulated, on the one
      hand, by the nanostructure of matrices, while on the other hand by the polymer
      concentration utilized for fabrication. As for hydrophilic compounds, they could
      be conveniently loaded into nanofibrous structure by post-fabrication absorption.
      In addition to the conceptual proof of potential applications of nanostructured
      PLLA matrices for controlled drug delivery, the strategy employed herein offers a
      new way to construct bioactive scaffolds, such as antibacterial or anti
      inflammatory scaffolds, which may find broad applications for tissue regeneration
      and stem cells-based biotherapy.

PMID- 23535344
TI  - Long chain lipid based tamoxifen NLC. Part II: pharmacokinetic, biodistribution
      and in vitro anticancer efficacy studies.
AB  - Long chain lipid (LCL) based tamoxifen loaded nanostructured lipid carriers (Tmx
      NLCs) meant to target intestinal lymphatic systems (ILSs) was developed and
      characterized previously. The aim of the present work was to evaluate in vitro
      efficacy of developed Tmx-NLC against breast cancer cell lines and to confirm the
      hypothesis of targeting ILS after single dose oral administration. In vitro
      anticancer activity of Tmx-NLC was assessed in human estrogen receptor expressing
      breast cancer cell lines viz. MCF-7 and ZR-75-1. The study revealed relatively
      improved activity for Tmx-NLC compared to free Tmx against MCF-7 cells. However,
      the activity was compromised against ZR-75-1 cells which could be attributed to
      its up regulation of MUC1 gene. Confocal and flow cytometric analysis revealed
      remarkable intracellular uptake of Tmx-NLC and its localization in nuclear and
      perinuclear region of cells. Tmx-NLC exhibited distinctly different
      pharmacokinetic profile compared to Tamoxifen suspension (Tmx-susp) and exhibited
      an increment in the bioavailability by 2.71-fold and prolonged the T1/2 by 7.10
      fold. Moreover, detectable drug concentration in mesenteric lymph nodes justifies
      our hypothesis of targeting ILS and explains the major uptake of Tmx to occur via
      lymphatic system.

PMID- 23535345
TI  - Long chain lipid based tamoxifen NLC. Part I: preformulation studies, formulation
      development and physicochemical characterization.
AB  - Tamoxifen citrate (Tmx) was formulated in nanostructured lipid carrier system
      (NLC) using long chain solid lipids (LCSL) and oils (LCO) with the aim to target
      lymphatic system to improve its bioavailability in plasma and lymphnode (initial
      sites for metastasis) and reduce its drug associated toxicity. Tamoxifen loaded
      NLC (Tmx-NLC) was formulated using solvent diffusion technique. Preformulation
      studies comprised evaluation of drug-excipients compatibility. Solubility of Tmx
      was screened in LCSL and LCO, surfactants and co-surfactants to identify NLC
      components. Surfactant co-surfactant combinations were studied for their ability
      to stabilize the system. Tmx-NLC was physicochemically characterized by TEM, DSC,
      XRD, and FTIR studies. Drug-excipients chemical compatibility study facilitated
      anticipation of excipients induced oxidative degradation of Tmx. Suitable storage
      condition below 30 degrees C could stabilize Tmx. Tmx-NLC with >90% entrapment
      efficiency and 215.60 +/- 7.98 nm particle size were prepared and freeze dried.
      Freeze dried Tmx-NLC could withstand various gastrointestinal tract (GI) media
      (pH 1.2, pH 3.5, pH 4.5, pH 6.8, pH 7.4). Dissolution profile of Tmx-NLC in
      various media showed sustained release pattern irrespective of pH of medium. No
      significant change in characteristics of Tmx-NLC was observed after 3 months of
      accelerated stability studies.

PMID- 23535346
TI  - Ligand-functionalized nanoliposomes for targeted delivery of galantamine.
AB  - The purpose of this study was to design ligand-functionalized nanoliposomes that
      are proficient in providing effective intracellular delivery of an alkaloid drug
      (galantamine) into PC12 neuronal cells in response to managing Alzheimer's
      disease (AD). Ligand-functionalized nanoliposomes were produced and validated for
      their physicochemical properties, in silico molecular mechanics energy
      relationships, ex vivo cytotoxicity, peptide coupling efficiency (PCE), drug
      entrapment efficiency (DEE), drug release, fluorometry and confocal microscopy.
      Particle sizes of the nanoliposomes ranged from 127 nm to 165 nm (PdI=0.39-0.03),
      zeta potential values of -18 mV to -36 mV, PCE from 40% to 78% while DEE ranged
      from 42% to 79%. The surface morphology of the nanoliposomes was stable,
      spherically and uniform in shape. Thermal behavior and Fourier transform infrared
      (FTIR) analyses confirmed that galantamine and the peptide-ligand were
      incorporated into the inner core and surface of the nanoliposomes, respectively.
      The optimized formulation showed sustained drug release (30% of drug released
      within 48 h). Fluorometry and confocal microscopy revealed that the ligand
      functionalized nanoliposomes facilitated galantamine uptake into PC12 neuronal
      cells via the Serpin Enzyme Complex Receptor in a mediated manner. CytoTox-GloTM
      cytotoxicity assay established the low cytotoxicity on PC12 neuronal cells when
      exposed to native nanoliposomes and the ligand-functionalized nanoliposomes.
      Response surface analysis demonstrated there was a high degree of correlation
      between the experimental and fitted values. Furthermore, ex vivo studies showed
      that the high galantamine accumulation into PC12 neuronal cells was influenced by
      the post-engineering of peptides on the surface of the galantamine-loaded
      nanoliposomes. MMER analysis aptly corroborated the experimental findings.

PMID- 23535347
TI  - Evaluation of cationic dendrimer and lipid as transfection reagents of short RNAs
      for stem cell modification.
AB  - Nowadays a large number of clinical trials suffer from lacking an efficient
      method for drug delivery into target cells with minimal side effects. Due to the
      great significance of this issue in novel and effective therapies, more attempts
      are required in order to distinguish better conditions for biomedical drug
      delivery. Since embryonic stem cells (ESCs) are under scrutiny of many new
      studies, development of novel methods for their genetical and functional
      modifications is of great value. On the other hand, the application of short
      nucleic acids in new therapeutic approaches is increasing. In this study the
      efficiency of small interfering RNA (siRNA) uptake with two transfection reagents
      generation five of polyamidoamine dendrimer (PAMAM G5) as a cationic dendrimer
      and N-[1-(2,3-dioleoyloxy)]-N,N,N-trimethylammonium propane methyl-sulfate
      (DOTAP) as a cationic lipid and one commercially available reagent were evaluated
      in mouse ESCs using flow cytometry. Prior to the cellular investigations; atomic
      force microscopy; gel electrophoresis; siRNA binding and release assays; and size
      and zeta potential measurements were utilized to characterize the physicochemical
      properties of reagent-siRNA nano-complexes. The safety of the nano-complexes was
      subsequently assessed by MTT assay. Functional effects of siRNA (complementary
      strand for OCT4 transcript) transfection in ESCs with the mentioned reagents were
      analyzed using a quantitative real-time polymerase chain reaction (qPCR).
      Surprisingly DOTAP at higher molar ratios and PAMAM at lower molar ratios could
      successfully knock down the OCT4 transcription relatively better than commercial
      reagent. Our findings supported the appropriate efficiency of the mentioned
      transfection reagents for short nucleic acid transfection. From a clinical point
      of view, this research helps allocation of short nucleic acids into stem cells
      therapies.

PMID- 23535348
TI  - Further evidence for involvement of the dorsal hippocampus serotonergic and gamma
      aminobutyric acid (GABA)ergic pathways in the expression of contextual fear
      conditioning in rats.
AB  - Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor
      agonist, were previously shown to inhibit the expression of contextual fear when
      administered six hours after conditioning. However, further understanding of the
      consolidation and expression of aversive memories requires investigations of
      these and other mechanisms at distinct time points and the regions of the brain
      to which they are transferred. Thus, the purpose of the present study was to
      investigate the role of DH serotonergic and gamma-aminobutyric acid (GABA)ergic
      mechanisms in the expression of contextual fear 24 h after conditioning,
      reflected by fear-potentiated startle (FPS) and freezing behavior. The
      recruitment of the amygdala and medial prefrontal cortex (mPFC) in these
      processes was also evaluated by measuring Fos protein immunoreactivity. Although
      intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol
      reduced both FPS and the freezing response. Fos protein immunoreactivity revealed
      that contextual fear promoted wide activation of the mPFC, which was
      significantly reduced after intra-DH infusions of muscimol. The present findings,
      together with previous data, indicate that in contrast to 5-HT, which appears to
      play a role during the early phases of contextual aversive memory consolidation,
      longer-lasting GABA-mediated mechanisms are recruited during the expression of
      contextual fear memories. 

PMID- 23535349
TI  - Risk of ischemic stroke with the use of risperidone, quetiapine and olanzapine in
      elderly patients: a population-based, case-crossover study.
AB  - We conducted a case-crossover study to evaluate the comparative risk of ischemic
      stroke associated with the use of risperidone, quetiapine and olanzapine in
      geriatric patients using the Korean Health Insurance Review and Assessment
      Service database. Cases included elderly patients >64 years old who had
      experienced their first ischemic stroke (International Classification of Disease,
      Tenth Revision (ICD-10), I63) hospitalization from July 2005 to June 2006 and who
      had been without prior cerebrovascular diseases (ICD-10, I60-I69), or transient
      ischemic attack (ICD-10, G45). Exposures to risperidone, quetiapine and
      olanzapine were assessed during the 30 days prior to the stroke episode. We set
      two control periods with lengths which were the same as the hazard periods.
      Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated by
      conditional logistic regression. A total of 1601 cases of ischemic stroke with a
      mean age of 75.6 (+/-6.7) years were identified, among which 933 (58.3%) were
      female. An increased risk of ischemic stroke was associated with the use of
      risperidone (aOR=3.5, 95% CI 3.3-4.6) and quetiapine (aOR=2.7, 95% CI 2.0-3.6)
      during the 30 days prior to stroke: however, no significant risk was observed
      with olanzapine (aOR=1.2, 95% CI 0.7-2.0). The increased stroke risk in demented
      patients, assessed within 30 days after exposure, was also observed with
      olanzapine. However, the sample of olanzapine users was small and underpowered. 

PMID- 23535350
TI  - Use of asenapine in clinical practice for the management of bipolar mania.
AB  - Bipolar disorder is a chronic mental illness associated with high levels of
      somatic morbidity, comorbidity and mortality. Treatment guidelines for bipolar
      mania generally recommend initiating first-line therapy with a second-generation
      antipsychotic or mood stabiliser, either alone or in combination. Asenapine is a
      second-generation antipsychotic with a unique receptor binding profile, licensed
      for the treatment of manic episodes in adults with bipolar I disorder. 'Real
      world' data are needed to complement evidence from clinical trials, in order to
      provide clinicians with pragmatic information regarding the likely risks and
      benefits of using a new agent in clinical practice. Evidence from real-world case
      reports demonstrates that - as in clinical trials - asenapine is effective in
      treating mania and mixed episodes associated with bipolar I disorder, whether
      used as monotherapy or in combination with a mood stabiliser. It has a rapid
      onset of antimanic effect and an early improvement is associated with treatment
      outcome. Asenapine also shows promise in controlling depressive symptoms and
      clinically challenging mixed states. Asenapine has a favourable tolerability
      profile, compared with other first-line agents, having a minimal impact on weight
      and metabolic parameters. Asenapine should be considered a first-line treatment
      option for adults with bipolar I disorder.

PMID- 23535351
TI  - Management of schizophrenia: clinical experience with asenapine.
AB  - Schizophrenia is a chronic brain disorder comprising a range of clinical
      features, including positive and negative symptoms, cognitive dysfunction and
      mood symptoms (particularly depression and anxiety). The management of
      schizophrenia requires effective short- and long-term treatment with
      antipsychotic medication that is effective across these symptom domains, while
      being well tolerated over the long term. Asenapine is the first tetracyclic
      atypical antipsychotic to be licensed in the USA and several other countries
      outside Europe for the acute and maintenance treatment of schizophrenia in
      adults. It has a unique receptor-binding profile and a broad range of therapeutic
      effects. Since clinical trials are conducted under strict conditions in tightly
      defined patient populations, evidence of an agent's efficacy and tolerability
      under 'real-world' clinical practice conditions is also required. As in clinical
      trials, real-life case reports demonstrate that asenapine is effective in
      treating the positive symptoms of schizophrenia, both in the acute setting and
      for relapse prevention. It is also effective in treating negative symptoms and
      shows promise in the treatment of depressive symptoms associated with
      schizophrenia. Asenapine has a favourable tolerability profile, having a minimal
      impact on weight and metabolic parameters. As such, asenapine is valuable option
      for the treatment of schizophrenia in adults.

PMID- 23535352
TI  - The role of serotonin in cognitive function: evidence from recent studies and
      implications for understanding depression.
AB  - BACKGROUND: Symptoms of cognitive impairment such as poor concentration, memory
      loss and difficulty with decision making are prevalent in patients with
      depression, but currently are not specific targets for treatment. However,
      patients can continue to demonstrate cognitive impairments even when apparently
      clinically recovered. Drugs that potentiate serotonin (5-HT) function, such as
      selective serotonin reuptake inhibitors (SSRIs), are the mainstay of treatment
      for depression. Nevertheless, our understanding of the effects of SSRIs and other
      conventional antidepressant therapy on cognitive function in healthy humans and
      depressed patients remains limited. OBJECTIVE: The purpose of this article is to
      provide a concise overview for clinicians on the impact of pharmacological
      manipulation of 5-HT on cognitive function in healthy humans with additional
      reference to animal models where human data are lacking, particularly regarding
      specific 5-HT receptor subtype modulation. FINDINGS: The most consistent
      observation following manipulation of serotonin levels in humans is that low
      extracellular 5-HT levels are associated with impaired memory consolidation.
      Preclinical data show that agonism and antagonism at specific 5-HT receptors can
      exert effects in animal models of cognition. CONCLUSIONS: Larger, consistently
      designed studies are needed to understand the roles of 5-HT in cognition in
      healthy and depressed individuals. Efforts to target specific 5-HT receptors to
      improve cognitive outcomes are warranted.

PMID- 23535353
TI  - Development of a validated patient satisfaction survey for HIV clinic attendees.
AB  - Patients are becoming more actively involved in decisions about their care and
      have greater influence to change and improve the quality of services by reporting
      their experiences. A recent systematic review failed to reveal a method of
      measuring HIV patient satisfaction that reflects their experience of contemporary
      treatment and care. The aim of this study was to design a specific HIV patient
      satisfaction questionnaire that can be used as a patient reported outcome
      measure. Key themes in the systematic review were identified and used as a topic
      guide for focus group discussion to confirm their relevance and importance. HIV
      patients were also interviewed about their motivation to complete a
      questionnaire. The data from the focus groups and interviews were used to develop
      an initial questionnaire and cognitive testing was used to provide face validity
      for the questionnaire design, layout and wording. A revised version was used in a
      pilot study of 80 respondents, which demonstrated that the questionnaire's
      completion rate and content validity were high. 

PMID- 23535354
TI  - Birds of a feather: homophily and sexual network structure in sub-Saharan Africa.
AB  - Sexual partner homophily is the tendency of individuals to choose partners
      similar to themselves. The extent and nature of partner homophily influences the
      structure of sexual networks and hence the spread of sexually transmitted
      infections (STIs). In this paper, we compare homophily by ethnicity, age and
      educational status in representative populations from five African cities in
      Benin (Cotonou), Cameroon (Yaounde), Kenya (Kisumu), Zambia (Ndola) and South
      Africa (Carletonville). We find low rates of homophily by age and high rates for
      educational status throughout the region. There is a large variation in homophily
      by ethnicity between these five cities, with rates lowest in Ndola. In
      Carletonville, there is a gendered difference in homophily by ethnicity. We
      discuss the possible implications these variations in the extent and type of
      homophily may have for STI transmission in the region. 

PMID- 23535355
TI  - Routine detection and management of neurocognitive impairment in HIV-positive
      patients in a UK centre.
AB  - We estimated the burden of HIV-associated neurocognitive disorders (HAND) in a UK
      clinic. From a random sample, and referrals to specialist services over one year
      (neurology, clinical psychology, hospital admissions), we determined whether
      patients were diagnosed with HIV-associated dementia (HAD) and whether they
      reported symptoms suggesting neurocognitive impairment (NCI). In the first
      sample, 2/150 (prevalence 1.3%; 95% confidence interval [CI] 0.2-4.7%) had
      documented HAD. Eleven patients (7.3%; CI 3.7-12.7%) reported recent symptoms
      suggesting NCI; most of these individuals were diagnosed with a psychiatric or
      substance-use disorder. Among specialist referrals with symptoms suggesting NCI,
      11 were diagnosed with HAD from a clinic population of 3129 individuals (annual
      incidence 0.4%; CI 0.2-0.6%). No patients with mildly symptomatic or asymptomatic
      HAND were identified in either sample, suggesting that such patients remain
      undetected in current clinical practice. Evidence-based screening for HAND in HIV
      clinics may be needed. 

PMID- 23535356
TI  - Treatment of high-grade anal dysplasia in high-risk patients: outcome at an urban
      community health centre.
AB  - Human immunodeficiency (HIV)-infected patients and men who have sex with men
      (MSM) have a higher rate of high-grade anal intraepithelial neoplasia (HGAIN), a
      likely precursor to anal cancer. This retrospective study describes the outcome
      of treating MSM with incident biopsy-proven HGAIN in an urban community health
      setting with access to outpatient ablation or operative treatment. The main
      outcome was freedom from HGAIN at follow-up. One hundred and fifty-three met
      inclusion criteria; 86 (56%) were HIV-infected. Eighty (52%) received outpatient
      ablation, 49 (61%) had a follow-up within nine months. Among those, 26 (53%) were
      free of high-grade disease, 19 (39%) had high-grade disease; and 4 (8%) had
      unknown grading. In a logistic regression model, a lower extent of anal disease
      (1 quadrant versus 2, 3 or 4 quadrants) at the time of treatment was
      significantly associated with a lower probability of high-grade disease (P value
      0.04). HGAIN could be managed in a community health setting; however, systems are
      needed to ensure follow-up care. 

PMID- 23535357
TI  - Multiple human papillomavirus infections and HIV seropositivity as risk factors
      for abnormal cervical cytology among female sex workers in Nairobi.
AB  - We estimated type-specific prevalence of human papillomavirus (HPV) and examined
      risk factors for abnormal cervical cytology among 296 female sex workers from
      Nairobi, Kenya. Over half (54%) were infected with a high-risk (HR) HPV type, of
      which HPV16 and 52 were the most common types. HIV-1 prevalence was 23% and HIV-1
      sero-positivity was associated with high-grade cervical lesions, particularly
      among women with CD4 count less than 500 cells/mm(3) (odds ratio [OR] = 6.9; 95%
      confidence interval [CI]: 1.7-24.9). Among women who had normal cytology at the
      time of entry into the study, the risk of having an abnormal Pap smear within one
      year was significantly elevated for women with multiple HPV types at study entry
      (adjusted odds ratio [aOR] = 6.0; 95% CI: 2.3-15.7) and with a subset of HR HPV
      types (aOR = 4.2; 95% CI: 1.6-11.2). Detection of multiple concurrent HPV
      infections may be a useful marker to identify women at risk of developing
      precancerous lesions in populations of high HPV prevalence. 

PMID- 23535358
TI  - Immunization against pneumococcal disease in HIV-infected patients: conjugate
      versus polysaccharide vaccine before or after reconstitution of the immune system
      (CTN-147).
AB  - To investigate whether patients should be immunized immediately or delay
      immunization until after reconstitution of the immune system and whether a
      conjugate or polysaccharide vaccine results in a better immunologic response.
      Seventy-nine patients were randomly assigned, utilizing a two by two factorial
      design to receive immediate immunization or delay immunization. Baseline
      characteristics were similar for the four arms: 78% men, median age 41 years,
      median time since HIV diagnosis 0.3 years, median CD4 60 cells/mm(3) and median
      HIV viral load 5.02 log copies/mL. Results in favour of delayed immunization were
      observed for those serotypes showing a response. The proportional odds ratios for
      delayed versus immediate immunization were 0.341 (P = 0.04) and 0.204 (P = 0.004)
      at months 6 and 12, respectively. No differences in immunological response were
      observed between the two individual vaccines for the shared serotypes studied.
      HIV-infected adults produced a higher immunological response to pneumococcal
      vaccine after reconstitution of the immune system. 

PMID- 23535359
TI  - Association of CYP11B2 polymorphisms with susceptibility to primary
      aldosteronism: a meta-analysis.
AB  - The association of CYP11B2 gene polymorphisms with the risk of primary
      aldosteronism (PA) was controversial in previous studies. Here we selected two
      commonly studied CYP11B2 alleles: T-344C, A2718G to explore their associations
      with PA risk by meta-analyses of published case-control studies. Six electronic
      databases were searched for relevant studies up to November 2012. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated using random or fixed
      effects model. Seven studies (621 cases and 1027 controls) on T-344C
      polymorphism, three studies (327 cases and 336 controls) on A2718G polymorphism
      were finally included. Then significant association was observed between T-344C
      polymorphism and idiopathic hyperaldosteronism (IHA) under three genetic models
      (CC vs. TT, OR=0.544, 95% CI=0.324~0.914; CT vs. TT, OR=0.554, 95%
      CI=0.406~0.757; CC+CT vs. TT, OR=0.542, 95% CI=0.402~0.731). But patients with
      aldosterone-producing adenoma had no significant association with T-344C
      polymorphism under all genetic models except CT vs. TT model. Concerning A2718G
      polymorphism, a decreased PA risk was observed only under GG+GA vs AA model. But
      this association disappeared after removing the studies not in Hardy-Weinberg
      equilibrium. The evidence accumulated suggested that -344C allele may be
      associated with decreased risk of IHA and there was still no enough evidence to
      indicate the association of A2718G polymorphism with PA risk.

PMID- 23535360
TI  - Reactivity of chemical sensitizers toward amino acids in cellulo plays a role in
      the activation of the Nrf2-ARE pathway in human monocyte dendritic cells and the
      THP-1 cell line.
AB  - Allergic contact dermatitis resulting from skin sensitization is an inflammatory
      skin disease linked to the use of chemicals termed haptens. Chemical reactivity
      is necessary for a chemical to be a sensitizer, allowing both covalent binding to
      proteins and maturation of dendritic cells (DCs) by mimicking "danger signals."
      The aim of this study was to evaluate how the reactivity of chemical sensitizers
      toward amino acids translates into a biological response using the activation of
      the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway, which was
      assessed by the induction of three Nrf2 target genes (ho-1, nqo1, and il-8) and
      Nrf2 protein accumulation. Nrf2 activation is known to play a role in numerous
      detoxification mechanisms that could regulate danger signal outcomes in myeloid
      cells. Monocyte-derived DCs and THP-1 cells were exposed to (a) haptens with
      cysteine, lysine, or cysteine/lysine reactivity, (b) pro-/prehaptens, and (c)
      nonsensitizing molecules with reducing or oxidative properties (17 molecules in
      total). Chemicals were classified as "Nrf2 pathway activators" when at least two
      Nrf2 target genes associated with Nrf2 protein expression were induced. Results
      showed that most chemical sensitizers having cysteine and cysteine/lysine
      affinities were inducers of the Nrf2 pathway in both cell models, whereas lysine
      reactive chemicals were less efficient. In THP-1 cells, the Nrf2 pathway was also
      activated by pro-/prehaptens. Regression analysis revealed that ho-1 and nqo1
      expressions were found to be associated with chemical sensitizer reactivity to
      cysteine, providing evidence of the importance of chemical reactivity, as a part
      of danger signals, in DC biology.

PMID- 23535361
TI  - Evaluation of perturbations in serum thyroid hormones during human pregnancy due
      to dietary iodide and perchlorate exposure using a biologically based dose
      response model.
AB  - A biologically based dose-response model (BBDR) for the hypothalamic pituitary
      thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This
      model was calibrated to predict serum levels of iodide, total thyroxine (T4),
      free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for
      a range of dietary iodide intake. The model was extended to describe perchlorate,
      an environmental and food contaminant, that competes with the sodium iodide
      symporter protein for thyroidal uptake of iodide. Using this mode-of-action
      framework, simulations were performed to determine the daily ingestion rates of
      perchlorate that would be associated with hypothyroxinemia or onset of
      hypothyroidism for varying iodide intake. Model simulations suggested that a
      maternal iodide intake of 75 to 250 ug/day and an environmentally relevant
      exposure of perchlorate (~0.1 ug/kg/day) did not result in hypothyroxinemia or
      hypothyroidism. For a daily iodide-sufficient intake of 200 ug/day, the dose of
      perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state
      was estimated at 32.2 ug/kg/day. As iodide intake was lowered to 75 ug/day, the
      model simulated daily perchlorate dose required to cause hypothyroxinemia was
      reduced by eightfold. Similarly, the perchlorate intake rates associated with the
      onset of subclinical hypothyroidism ranged from 54.8 to 21.5 ug/kg/day for daily
      iodide intake of 250-75 ug/day. This BBDR-HPT axis model for pregnancy provides
      an example of a novel public health assessment tool that may be expanded to
      address other endocrine-active chemicals found in food and the environment.

PMID- 23535362
TI  - Specific pesticide-dependent increases in alpha-synuclein levels in human
      neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.
AB  - Epidemiological studies indicate a role of genetic and environmental factors in
      Parkinson's disease involving alterations of the neuronal alpha-synuclein (alpha
      syn) protein. In particular, a relationship between Parkinson's disease and
      occupational exposure to pesticides has been repeatedly suggested. Our objective
      was to precisely assess changes in alpha-syn levels in human neuroblastoma (SH
      SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides
      (rotenone, paraquat, maneb, and glyphosate) using Western blot and flow
      cytometry. These human cell lines express alpha-syn endogenously, and
      overexpression of alpha-syn (wild type or mutated A53T) can be obtained following
      recombinant adenoviral transduction. We found that endogenous alpha-syn levels in
      the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a
      lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly
      increased endogenous alpha-syn levels in the SK-MEL-2 melanoma cell line. In the
      SH-SY5Y cell line, similar differences were observed in the alpha-syn adenovirus
      transduced cells, with a higher increase of the A53T mutated protein. Paraquat
      markedly increased alpha-syn in the SK-MEL-2 adenovirus-transduced cell line,
      similarly for the wild-type or A53T proteins. The observed differences in the
      propensities of pesticides to increase alpha-syn levels are in agreement with
      numerous reports that indicate a potential role of exposure to certain pesticides
      in the development of Parkinson's disease. Our data support the hypothesis that
      pesticides can trigger some molecular events involved in this disease and also in
      malignant melanoma that consistently shows a significant but still unexplained
      association with Parkinson's disease.

PMID- 23535363
TI  - Interferon-gamma promoter is hypermethylated in blood DNA from workers with
      confirmed diisocyanate asthma.
AB  - Risk factors have not been identified that determine susceptibility for
      development of diisocyanate-induced occupational asthma (DA). We hypothesized
      that diisocyanate (DI) exposure could modify gene promoter regions regulating
      transcription of cytokine mediators and thereby influence expression of DA. A
      cross-sectional study was designed to investigate the promoter methylation status
      of candidate genes in DI-exposed workers. Subjects consisted of 131 workers in
      three groups: 40 cases with DA confirmed by a positive specific inhalation
      challenge (SIC) (DA+), 41 exposed workers with lower respiratory symptoms and
      negative SIC (DA-), and 50 asymptomatic exposed workers (AWs). We studied four
      candidate genes (GSTM1, DUSP22, IFN-gamma, and IL-4) for which altered promoter
      methylation has been previously investigated for relationships with a variety of
      other environmental exposures. Methylation status was determined using
      methylation-specific quantitative PCR performed on genomic DNA extracted from
      whole blood. Results showed that relative methylation of IFN-gamma promoter was
      significantly increased in DA+ in comparison with both comparator groups (DA- and
      AW), and it exhibited good sensitivity (77.5%) and specificity (80%) for
      identifying DA workers in a multivariate predictive model after adjusting for
      type of DI exposure, smoking status, methacholine PC20, and gender. IL-4 promoter
      was slightly less methylated only in DA+ compared with AW among nonsmoking
      workers. Both GSTM1 and DUSP22 promoter methylations were found not associated
      with DA. Our finding suggests that exposure to occupational chemicals could play
      a heretofore undefined mechanistic role via epigenetic modification of specific
      genes in the promoter region.

PMID- 23535364
TI  - DNA adduct formation of 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline in mouse liver and extrahepatic tissues during a
      subchronic feeding study.
AB  - Tobacco smoking is a risk factor for cancers of the liver and gastrointestinal
      (GI) tract, but the causal agents responsible for these cancers are uncertain. 2
      Amino-9H-pyrido[2,3-b]indole (AalphaC) is an abundant heterocyclic aromatic amine
      present in tobacco smoke. AalphaC is a liver carcinogen and both a transgene
      mutagen and inducer of aberrant crypt foci in the colon of mice. We hypothesize
      that AalphaC may contribute to DNA damage and tumorigenesis in these organs of
      smokers. The potential of AalphaC to induce DNA adduct formation in liver, organs
      of the GI tract, lung, and urinary bladder, which are target organs of cancer in
      smokers, was examined using the C57BL/6 mouse as an animal model. AalphaC (400 or
      800 ppm) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) (300 ppm), a
      liver and colon carcinogen in C57BL/6 mice, were given in the diet for up to 12
      weeks. Liquid chromatography/mass spectrometry was employed to measure DNA
      adducts. The major DNA adducts of both carcinogens were identified as
      deoxyguanosine-C8 adducts. The levels of formation of AalphaC- and MeIQ-DNA
      adducts were similar in liver and extrahepatic tissues when adjusted for dose.
      The highest levels of adducts occurred in liver, followed by urinary bladder, and
      then in cecum and colon; lower DNA adduct levels were formed in the lung and
      pancreas following 12 weeks of feeding. The high levels of AalphaC adduct formed
      in liver, GI tract, and bladder of C57BL/6 mice reinforce the notion that AalphaC
      may contribute to DNA damage and cancer of these organs in smokers.

PMID- 23535365
TI  - Living in the moment: patients with MTL amnesia can richly describe the present
      despite deficits in past and future thought.

PMID- 23535366
TI  - Chitin-natural clay nanotubes hybrid hydrogel.
AB  - Novel hybrid hydrogel was synthesized from chitin NaOH/urea aqueous solution in
      presence of halloysite nanotubes (HNTs) via crosslinking with epichlorohydrin.
      Fourier transform infrared (FT-IR) spectra and atomic force microscopy (AFM)
      results confirmed the interfacial interactions in the chitin-HNTs hybrid
      hydrogel. The compressive strength and shear modulus of chitin hydrogel were
      significantly increased by HNTs as shown in the static compressive experiment and
      rheology measurement. The hybrid hydrogels showed highly porous microstructures
      by scanning electron microscopy (SEM). The swelling ratio of chitin hydrogel
      decreased because of the addition of HNTs. The malachite green's absorption
      experiment result showed that the hybrid hydrogel exhibited much higher
      absorption rate than the pure chitin hydrogel. The prepared hybrid hydrogel had
      potential applications in waste treatment and biomedical areas.

PMID- 23535372
TI  - Guns, germs, and stealing: exploring the link between infectious disease and
      crime.
AB  - Can variation in crime rates be traced to the threat of infectious disease?
      Pathogens pose an ongoing challenge to survival, leading humans to adapt defenses
      to manage this threat. In addition to the biological immune system, humans have
      psychological and behavioral responses designed to protect against disease. Under
      persistent disease threat, xenophobia increases and people constrict social
      interactions to known in-group members. Though these responses reduce disease
      transmission, they can generate favorable crime conditions in two ways. First,
      xenophobia reduces inhibitions against harming and exploiting out-group members.
      Second, segregation into in-group factions erodes people's concern for the
      welfare of their community and weakens the collective ability to prevent crime.
      The present study examined the effects of infection incidence on crime rates
      across the United States. Infection rates predicted violent and property crime
      more strongly than other crime covariates. Infections also predicted homicides
      against strangers but not family or acquaintances, supporting the hypothesis that
      in-group-out-group discrimination was responsible for the infections-crime link.
      Overall, the results add to evidence that disease threat shapes interpersonal
      behavior and structural characteristics of groups.

PMID- 23535373
TI  - Exercise ameliorates cognition impairment due to restraint stress-induced
      oxidative insult and reduced BDNF level.
AB  - We assessed whether chronic treadmill exercise attenuated restraint stress
      induced cognition impairment. Although serum corticosterone was not significantly
      altered by exercise, the restraint-induced increases in hippocampal
      malondialdehyde (MDA) and 4-hydroxynonenal (HNE) were reduced by chronic
      exercise. The exercise paradigm also reversed stress-induced reductions in brain
      derived neurotrophic factor (BDNF), which increased cAMP response element-binding
      protein (CREB) and AKT activation. We verified the relationship between oxidative
      stress and BDNF signaling by treating primary hippocampal cultures with hydrogen
      peroxide (H2O2), which reduced BDNF and phosphorylated CREB and AKT (p-CREB, p
      AKT) in a dose-dependent manner. Notably, pretreatment with N-acetylcysteine
      (NAC) reversed these decreases in a dose-dependent manner. These findings suggest
      that chronic exercise can ameliorate repeated stress-induced cognitive impairment
      by detoxifying reactive oxygen species (ROS) in the hippocampus and activating
      BDNF signaling.

PMID- 23535374
TI  - Oxidized silicon nanoparticles for radiosensitization of cancer and tissue cells.
AB  - The applicability of ultrasmall uncapped and aminosilanized oxidized silicon
      nanoparticles (SiNPs and NH2-SiNPs) as radiosensitizer was studied by
      internalizing these nanoparticles into human breast cancer (MCF-7) and mouse
      fibroblast cells (3T3) that were exposed to X-rays at a single dose of 3 Gy.
      While SiNPs did not increase the production of reactive oxygen species (ROS) in X
      ray treated cells, the NH2-SiNPs significantly enhanced the ROS formation. This
      is due to the amino functionality as providing positive surface charges in
      aqueous environment. The NH2-SiNPs were observed to penetrate into the
      mitochondrial membrane, wherein these nanoparticles provoked oxidative stress.
      The NH2-SiNPs induced mitochondrial ROS production was confirmed by the
      determination of an increased malondialdehyde level as representing a gauge for
      the extent of membrane lipid peroxidation. X-ray exposure of NH2-SiNPs incubated
      MCF-7 and 3T3 cells increased the ROS concentration for 180%, and 120%,
      respectively. Complementary cytotoxicity studies demonstrate that these silicon
      nanoparticles are more cytotoxic for MCF-7 than for 3T3 cells.

PMID- 23535375
TI  - Interleukin-27 treated human macrophages induce the expression of novel microRNAs
      which may mediate anti-viral properties.
AB  - Interleukin-27 (IL-27) is a pleiotropic cytokine which plays important and
      diverse roles in the immune system. We have previously demonstrated that IL-27
      induces potent anti-viral effects against HIV-1, HIV-2, SIV, HSV-2, KSHV and
      influenza viruses in macrophages. This induction occurred in an interferon (IFN)
      independent manner and involved down regulation of SPTBN1. MicroRNAs (miRNAs) are
      critical regulators of mRNA translation and turnover. There have been reports
      that some miRNAs inhibit viral replication. In this study, we hypothesized that
      IL-27 could induce the expression of novel miRNAs in macrophages which may have
      functional relevance in terms of anti-viral activity and primary monocytes were
      differentiated into macrophages using either M-CSF (M-Mac) or a combination of M
      CSF and IL-27 (I-Mac) for seven days. Following this, total RNA was extracted
      from these cells and deep sequencing was performed, in parallel with gene
      expression microarrays. Using the novel miRNA discovery software, miRDeep, seven
      novel miRNAs were discovered in these macrophages. Four of which were
      preferentially expressed in I-Mac (miR-SX1, -SX2, -SX3 and -SX6) whilst three
      were detected in both M-Mac and I-Mac (miR-SX4, -SX5 and -SX7). The expression of
      six of the seven novel miRNAs was highly correlated with qRT-PCR using specific
      primer/probes designed for the novel miRNAs. Gene expression microarray further
      demonstrated that a number of genes were potentially targeted by these
      differentially expressed novel miRNAs. Finally, several of these novel miRNAs
      (miR-SX1, -SX4, -SX5, -SX6 and -SX7) were shown to target the open reading frames
      of a number of viruses (including HSV-1, HSV-2 and HHV-8) which may partially
      explain the anti-viral properties observed.

PMID- 23535376
TI  - Optimal microscopic systems for long-term imaging of intracellular calcium using
      a ratiometric genetically-encoded calcium indicator.
AB  - Monitoring the pattern of intracellular Ca(2+) signals that control many diverse
      cellular processes is essential for understanding regulatory mechanisms of
      cellular functions. Various genetically encoded Ca(2+) indicators (GECIs) are
      used for monitoring intracellular Ca(2+) changes under several types of
      microscope systems. However, it has not yet been explored which microscopic
      system is ideal for long-term imaging of the spatiotemporal patterns of Ca(2+)
      signals using GECIs. We here compared the Ca(2+) signals reported by a
      fluorescence resonance energy transfer (FRET)-based ratiometric GECI, yellow
      cameleon 3.60 (YC3.60), stably expressed in DT40 B lymphocytes, using three
      different imaging systems. These systems included a wide-field fluorescent
      microscope, a multipoint scanning confocal system, and a single-point scanning
      confocal system. The degree of photobleaching and the signal-to-noise ratio of
      YC3.60 in DT40 cells were highly dependent on the fluorescence excitation method,
      although the total illumination energy was maintained at a constant level within
      each of the imaging systems. More strikingly, the Ca(2+) responses evoked by B
      cell antigen receptor stimulation in YC3.60-expressing DT40 cells were different
      among the imaging systems, and markedly affected by the illumination power used.
      Our results suggest that optimization of the imaging system, including
      illumination and acquisition conditions, is crucial for accurate visualization of
      intracellular Ca(2+) signals.

PMID- 23535377
TI  - Beta-actin variant is necessary for Enterovirus 71 replication.
AB  - Enterovirus 71 (EV71) is one of the main etiological agents of the Hand, Foot and
      Mouth Disease (HFMD) and has been known to cause fatal neurological complications
      such as herpangina, aseptic meningitis, poliomyelitis-like paralysis and
      encephalitis. EV71 is endemic in the Asia-Pacific region and causes occasional
      epidemics. In order to better understand EV71 infection, we compared the proteome
      between EV71-susceptible and EV71-resistant human Rhabdomyosarcoma (RD) cell
      line. We found significant differences in the beta-actin variants between the
      EV71-susceptible RD cells and EV71-resistant RD cells, suggesting that beta
      actin, in association with other proteins such as annexin 2 is required in
      vesicular transport of EV71. This finding further support our previous study that
      actin potentially plays a role in pathogenesis and the establishment of the
      disease in HFMD.

PMID- 23535378
TI  - Detection and quantification of classic and emerging viruses by skimmed-milk
      flocculation and PCR in river water from two geographical areas.
AB  - Molecular techniques and virus concentration methods have shown that previously
      unknown viruses are shed by humans and animals, and may be transmitted by sewage
      contaminated water. In the present study, 10-L river-water samples from urban
      areas in Barcelona, Spain and Rio Janeiro, Brazil, have been analyzed to evaluate
      the viral dissemination of human viruses, validating also a low-cost
      concentration method for virus quantification in fresh water. Three viral groups
      were analyzed: (i) recently reported viruses, klassevirus (KV), asfarvirus-like
      virus (ASFLV), and the polyomaviruses Merkel cell (MCPyV), KI (KIPyV) and WU
      (WUPyV); (ii) the gastroenteritis agents noroviruses (NoV) and rotaviruses (RV);
      and (iii) the human fecal viral indicators in water, human adenoviruses (HAdV)
      and JC polyomaviruses (JCPyV). Virus detection was based on nested and
      quantitative PCR assays. For KV and ASFLV, nested PCR assays were developed for
      the present study. The method applied for virus concentration in fresh water
      samples is a one-step procedure based on a skimmed-milk flocculation procedure
      described previously for seawater. Using spiked river water samples, inter- and
      intra-laboratory assays showed a viral recovery rate of about 50% (20-95%) for
      HAdV, JCPyV, NoV and RV with a coefficient of variation <= 50%. HAdV and JCPyV
      were detected in 100% (12/12) of the river samples from Barcelona and Rio de
      Janeiro. Moreover, NoV GGII was detected in 83% (5/6) and MCPyV in 50% (3/6) of
      the samples from Barcelona, whereas none of the other viruses tested were
      detected. NoV GGII was detected in 33% (2/6), KV in 33% (2/6), ASFLV in 17% (1/6)
      and MCPyV in 50% (3/6) of the samples from Rio de Janeiro, whereas KIPyV and
      WUPyV were not detected. RV were only analyzed in Rio de Janeiro and resulted
      positive in 67% (4/6) of the samples. The procedure applied here to river water
      represents a useful, straightforward and cost-effective method that could be
      applied in routine water quality testing. The results of the assays expand our
      understanding of the global distribution of the viral pathogens studied here and
      their persistence in the environment.

PMID- 23535379
TI  - Characteristics of C-, N-DBPs formation from nitrogen-enriched dissolved organic
      matter in raw water and treated wastewater effluent.
AB  - The objective of this study is to clarify the relationships between the
      characteristics of dissolved organic nitrogen (DON) and disinfection by-products
      (DBPs) formation. Treated wastewater effluents from the Neihu wastewater
      treatment plant in Taipei City (TN) and source waters from the Tai Lake water
      treatment plant in Kinmen (KT) were evaluated. These water samples were
      fractionated to obtain 7 DON isolates with different characteristics. The DON
      isolates were freeze-dried and re-dissolved to different DON fraction solutions
      containing 10 mg-C/L of non-purgeable dissolved organic carbon (NPDOC). The DBPs
      formation potentials (DBPFPs) (trihalomethanes (THMs), haloacetic acids (HAAs),
      and nitrosamines) of different DON fraction solutions were then assessed with
      chlorine and monochloramine treatments. After fractionation schemes, mass
      concentrations of dried DON-enriched isolates ranged from 0.2 to 46.4 mg/L. Both
      TN effluents and KT raw waters had similar compositions of DON fractions except
      for the amounts of amphiphilic bases/neutrals (AMPB/N) isolates: hydrophobic
      acids (HPOA) > hydrophilic acids/neutrals (HPIA/N) > AMPB/N of KT raw waters >
      hydrophilic bases (HPIB) > amphiphilic acids (AMPA) > hydrophobic bases/neutrals
      (HPOB/N) > AMPB/N of TN effluents > amino acids (AA). For carbonated DBPs (C
      DBPs), AA fraction treated with NaOCl formed the greatest amounts of C-DBPs (up
      to 1258.2 MUg/L of THMs and 1140.6 MUg/L of HAAs). For nitrogenated DBPs (N
      DBPs), the AMPB/N fraction (DON = 1.4 mg-N/L) treated with NH2Cl was the most
      important precursor to form N-nitrosodimethylamine (NDMA) and generated up to
      9238.0 ng/L of NDMA from KT raw water. Taking both DBP formation and organic
      composition into account, the HPOA (31.9%-38.4%)/HPIA/N (17.6%-35.7%) fractions
      and AMPB/N fraction (38.4%-93.9%) were the most important contributors to the
      overall C-DBPFPs and N-DBPFPs, respectively.

PMID- 23535380
TI  - Impact of bilateral cataract surgery on vision-related activity limitations.
AB  - PURPOSE: To evaluate patients' vision-related activity limitation before and
      after bilateral cataract surgery using the German version of the Catquest-9SF
      questionnaire. SETTING: Hanusch Hospital, Vienna, Austria, and Ophthalmic Clinic,
      Minden, Germany. DESIGN: Questionnaire development. METHODS: This prospective 2
      center study included patients who were scheduled for bilateral cataract surgery
      and attended their preassessment appointment approximately 1 week before cataract
      surgery. All patients self-administered the Catquest-9SF at the preassessment
      session and a second time 3 months after cataract surgery. The questionnaire
      includes 9 items and is a revised short form of the Catquest, scored using Rasch
      analysis. The Catquest-9SF includes questions concerning vision-associated
      problems in everyday life, general satisfaction with vision, and difficulties
      performing activities. RESULTS: The study comprised 210 patients, 120 in Austria
      and 90 in Germany. The mean age of all patients was 74.1 years (range 41 to 92
      years). Patients mostly had difficulties doing handwork (42%) or recognizing
      uneven surfaces (30%). Sixty percent of the patients in Austria and approximately
      50% in Germany were very unsatisfied with their vision preoperatively.
      Postoperatively, all patients recognized a subjective improvement in their
      vision. CONCLUSIONS: Patients having bilateral cataract surgery achieved marked
      improvements in vision-related activity limitation and satisfaction with vision.
      A subset of patients with less vision-related activity limitation before surgery
      was satisfied with first-eye surgery only.

PMID- 23535381
TI  - Supplementary effect of static cyclotorsion compensation with dynamic
      cyclotorsion compensation on the refractive and visual outcomes of laser in situ
      keratomileusis for myopic astigmatism.
AB  - PURPOSE: To evaluate the add-on effect of static cyclotorsion compensation (SCC)
      over dynamic cyclotorsion compensation (DCC) on the refractive and visual
      outcomes in patients having laser in situ keratomileusis (LASIK) for myopic
      astigmatism. SETTING: Private center, Tokyo, Japan. DESIGN: Comparative study.
      METHODS: Consecutive patients had LASIK with a target of emmetropia between
      August 2009 and June 2010. Patients had preoperative myopic astigmatism of 2.0
      diopters (D) or greater and more than 3 months of follow-up. Patients had SCC
      plus DCC treatment (study group) or DCC treatment only (control group). RESULTS:
      The 2 groups were similar preoperatively in refraction, visual acuity, and higher
      order aberrations (HOAs). After treatment, the refractive outcome in the study
      group was significantly better than in the control group, with a mean sphere of
      0.13 D +/- 0.29 (SD) versus 0.17 +/- 0.30 D (P=.009), a mean cylinder of -0.11 +/
      0.29 D versus -0.19 +/- 0.36 D (P<.001), and a mean spherical equivalent of 0.07
      +/- 0.29 D versus 0.08 +/- 0.32 D (P=.020). Astigmatism vector analysis also
      yielded better outcomes in the study group. However, the 2 groups were
      statistically similar in postoperative uncorrected and corrected visual acuities
      and induced HOAs. The mean static cyclotorsion value in the study group was 2.29
      +/- 1.74 degrees (range 0 to 11.1 degrees). CONCLUSION: The combination of SCC
      and DCC using an aberration-free aspheric ablation profile produced a
      statistically significant improvement in astigmatism outcomes.

PMID- 23535382
TI  - How biochemical constraints of cellular growth shape evolutionary adaptations in
      metabolism.
AB  - Evolutionary adaptations in metabolic networks are fundamental to evolution of
      microbial growth. Studies on unneeded-protein synthesis indicate reductions in
      fitness upon nonfunctional protein synthesis, showing that cell growth is limited
      by constraints acting on cellular protein content. Here, we present a theory for
      optimal metabolic enzyme activity when cells are selected for maximal growth rate
      given such growth-limiting biochemical constraints. We show how optimal enzyme
      levels can be understood to result from an enzyme benefit minus cost
      optimization. The constraints we consider originate from different biochemical
      aspects of microbial growth, such as competition for limiting amounts of
      ribosomes or RNA polymerases, or limitations in available energy. Enzyme benefit
      is related to its kinetics and its importance for fitness, while enzyme cost
      expresses to what extent resource consumption reduces fitness through constraint
      induced reductions of other enzyme levels. A metabolic fitness landscape is
      introduced to define the fitness potential of an enzyme. This concept is related
      to the selection coefficient of the enzyme and can be expressed in terms of its
      fitness benefit and cost.

PMID- 23535383
TI  - Suppression of chromosome healing and anticheckpoint pathways in yeast
      postsenescence survivors.
AB  - Telomere repeat-like sequences at DNA double-strand breaks (DSBs) inhibit DNA
      damage signaling and serve as seeds to convert DSBs to new telomeres in mutagenic
      chromosome healing pathways. We find here that the response to seed-containing
      DSBs differs fundamentally between budding yeast (Saccharomyces cerevisiae) cells
      that maintain their telomeres via telomerase and so-called postsenescence
      survivors that use recombination-based alternative lengthening of telomere (ALT)
      mechanisms. Whereas telomere seeds are efficiently elongated by telomerase, they
      remain remarkably stable without de novo telomerization or extensive end
      resection in telomerase-deficient (est2Delta, tlc1Delta) postsenescence
      survivors. This telomere seed hyper-stability in ALT cells is associated with,
      but not caused by, prolonged DNA damage checkpoint activity (RAD9, RAD53)
      compared to telomerase-positive cells or presenescent telomerase-negative cells.
      The results indicate that both chromosome healing and anticheckpoint activity of
      telomere seeds are suppressed in yeast models of ALT pathways.

PMID- 23535384
TI  - Genomic predictability of interconnected biparental maize populations.
AB  - Intense structuring of plant breeding populations challenges the design of the
      training set (TS) in genomic selection (GS). An important open question is how
      the TS should be constructed from multiple related or unrelated small biparental
      families to predict progeny from individual crosses. Here, we used a set of five
      interconnected maize (Zea mays L.) populations of doubled-haploid (DH) lines
      derived from four parents to systematically investigate how the composition of
      the TS affects the prediction accuracy for lines from individual crosses. A total
      of 635 DH lines genotyped with 16,741 polymorphic SNPs were evaluated for five
      traits including Gibberella ear rot severity and three kernel yield component
      traits. The populations showed a genomic similarity pattern, which reflects the
      crossing scheme with a clear separation of full sibs, half sibs, and unrelated
      groups. Prediction accuracies within full-sib families of DH lines followed
      closely theoretical expectations, accounting for the influence of sample size and
      heritability of the trait. Prediction accuracies declined by 42% if full-sib DH
      lines were replaced by half-sib DH lines, but statistically significantly better
      results could be achieved if half-sib DH lines were available from both instead
      of only one parent of the validation population. Once both parents of the
      validation population were represented in the TS, including more crosses with a
      constant TS size did not increase accuracies. Unrelated crosses showing opposite
      linkage phases with the validation population resulted in negative or reduced
      prediction accuracies, if used alone or in combination with related families,
      respectively. We suggest identifying and excluding such crosses from the TS.
      Moreover, the observed variability among populations and traits suggests that
      these uncertainties must be taken into account in models optimizing the
      allocation of resources in GS.

PMID- 23535385
TI  - Improving the accuracy and efficiency of identity-by-descent detection in
      population data.
AB  - Segments of indentity-by-descent (IBD) detected from high-density genetic data
      are useful for many applications, including long-range phase determination,
      phasing family data, imputation, IBD mapping, and heritability analysis in
      founder populations. We present Refined IBD, a new method for IBD segment
      detection. Refined IBD achieves both computational efficiency and highly accurate
      IBD segment reporting by searching for IBD in two steps. The first step
      (identification) uses the GERMLINE algorithm to find shared haplotypes exceeding
      a length threshold. The second step (refinement) evaluates candidate segments
      with a probabilistic approach to assess the evidence for IBD. Like GERMLINE,
      Refined IBD allows for IBD reporting on a haplotype level, which facilitates
      determination of multi-individual IBD and allows for haplotype-based downstream
      analyses. To investigate the properties of Refined IBD, we simulate SNP data from
      a model with recent superexponential population growth that is designed to match
      United Kingdom data. The simulation results show that Refined IBD achieves a
      better power/accuracy profile than fastIBD or GERMLINE. We find that a single run
      of Refined IBD achieves greater power than 10 runs of fastIBD. We also apply
      Refined IBD to SNP data for samples from the United Kingdom and from Northern
      Finland and describe the IBD sharing in these data sets. Refined IBD is powerful,
      highly accurate, and easy to use and is implemented in Beagle version 4.

PMID- 23535386
TI  - Signalling by the betac family of cytokines.
AB  - The GM-CSF, IL-3 and IL-5 family of cytokines, also known as the betac family due
      to their receptors sharing the signalling subunit betac, regulates multiple
      biological processes such as native and adaptive immunity, inflammation, normal
      and malignant hemopoieis, and autoimmunity. Australian scientists played a major
      role in the discovery and biological characterisation of the betac cytokines and
      their recent work is revealing unique features of cytokine receptor assembly and
      signalling. Furthermore, specific antibodies have been generated to modulate
      their function. Characterisation of the structural and dynamic requirements for
      the activation of the betac receptor family and the molecular definition of
      downstream signalling pathways are providing new insights into cytokine receptor
      signalling as well as new therapeutic opportunities. 

PMID- 23535387
TI  - Melt compounding with graphene to develop functional, high-performance
      elastomers.
AB  - Rather than using graphene oxide, which is limited by a high defect concentration
      and cost due to oxidation and reduction, we adopted cost-effective, 3.56 nm thick
      graphene platelets (GnPs) of high structural integrity to melt compound with an
      elastomer-ethylene-propylene-diene monomer rubber (EPDM)-using an industrial
      facility. An elastomer is an amorphous, chemically crosslinked polymer generally
      having rather low modulus and fracture strength but high fracture strain in
      comparison with other materials; and upon removal of loading, it is able to
      return to its original geometry, immediately and completely. It was found that
      most GnPs dispersed uniformly in the elastomer matrix, although some did form
      clusters. A percolation threshold of electrical conductivity at 18 vol% GnPs was
      observed and the elastomer thermal conductivity increased by 417% at 45 vol%
      GnPs. The modulus and tensile strength increased by 710% and 404% at 26.7 vol%
      GnPs, respectively. The modulus improvement agrees well with the Guth and Halpin
      Tsai models. The reinforcing effect of GnPs was compared with silicate layers and
      carbon nanotube. Our simple fabrication would prolong the service life of
      elastomeric products used in dynamic loading, thus reducing thermosetting waste
      in the environment.

PMID- 23535388
TI  - Preinjury coping, emotional functioning, and quality of life following
      uncomplicated and complicated mild traumatic brain injury.
AB  - OBJECTIVE: To identify preinjury coping profiles among adults with uncomplicated
      mild traumatic brain injury (mTBI) and complicated mTBI and to determine whether
      preinjury coping profiles contribute to the prediction of emotional functioning
      and quality of life (QOL) 3 months post-mTBI. PARTICIPANTS: One hundred eighty
      seven persons with medically documented mTBI (uncomplicated mTBI, n = 89;
      complicated mTBI, n = 98) were recruited from the emergency center of a level I
      trauma center and followed in community 3 months post-mTBI. MEASURES: The Ways of
      Coping Questionnaire was administered within 2 weeks of injury. Cluster analysis
      was used to group participants on basis of their preinjury use of problem-focused
      and avoidant coping strategies. The Brief Symptom Inventory and the 36-item Short
      Form Health Survey were administered 3 months postinjury. RESULTS: Cluster
      analysis distinguished 3 distinct preinjury coping profiles that were
      differentially associated with outcomes. Participants who used avoidant coping
      showed the worse emotional functioning and QOL outcomes, although this cluster
      also reported high usage of problem-focused strategies. Preinjury coping profiles
      explained a significant proportion of the variance in depression, anxiety, and
      mental health QOL at 3 months postinjury beyond that accounted for by demographic
      characteristics and mTBI severity. CONCLUSIONS: Cluster analysis holds practical
      value in illustrating the pattern of coping strategies used by person with
      uncomplicated and complicated mTBI. It appears worthwhile to address coping in
      future trials of interventions that are aimed at improving emotional functioning
      after mTBI.

PMID- 23535389
TI  - The Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) semistructured
      interview: evidence of research utility and validity.
AB  - OBJECTIVE: Report the prevalence of lifetime and military-related traumatic brain
      injuries (TBIs) in Operation Enduring Freedom and Operation Iraqi Freedom
      (OEF/OIF) veterans and validate the Boston Assessment of TBI-Lifetime (BAT-L).
      SETTING: The BAT-L is the first validated, postcombat, semistructured clinical
      interview to characterize head injuries and diagnose TBIs throughout the life
      span. PARTICIPANTS: Community-dwelling convenience sample of 131 OEF/OIF
      veterans. DESIGN: TBI criteria (alteration of mental status, posttraumatic
      amnesia, and loss of consciousness) were evaluated for all possible TBIs,
      including a novel evaluation of blast exposure. MAIN MEASURES: BAT-L, Ohio State
      University TBI Identification Method (OSU-TBI-ID). RESULTS: About 67% of veterans
      incurred a TBI in their lifetime. Almost 35% of veterans experienced at least 1
      military-related TBI; all were mild in severity, 40% of them were due to blast,
      50% were due to some other (ie, blunt) mechanism, and 10% were due to both types
      of injuries. Predeployment TBIs were frequent (45% of veterans). There was strong
      correspondence between the BAT-L and the OSU-TBI-ID (Cohen kappa = 0.89; Kendall
      tau-b = 0.95). Interrater reliability of the BAT-L was strong (kappas >0.80).
      CONCLUSIONS: The BAT-L is a valid instrument with which to assess TBI across a
      service member's lifetime and captures the varied and complex nature of brain
      injuries across OEF/OIF veterans' life span.

PMID- 23535390
TI  - Psychotic symptoms as manifestations of the posttraumatic confusional state:
      prevalence, risk factors, and association with outcome.
AB  - OBJECTIVES: To (1) determine factors associated with psychotic-type symptoms in
      persons with moderate or severe traumatic brain injury (TBI) during early
      recovery and (2) investigate the prognostic significance of early psychotic-type
      symptoms for patient outcome. SETTING: Acute neurorehabilitation inpatient unit.
      PARTICIPANTS: A total of 168 persons with moderate or severe TBI were admitted
      for inpatient rehabilitation. Of these, 107 had psychotic-type symptoms on at
      least 1 examination. One-year productivity outcome was available for 87 of the
      107 participants. DESIGN: Prospective, inception cohort, observational study.
      MAIN MEASURES: Confusion Assessment Protocol, productivity outcome at 1 year
      postinjury. RESULTS: Presence of sleep disturbance, a shorter interval from
      admission to assessment, and greater cognitive impairment were associated with a
      greater incidence of psychotic-type symptoms. Younger age, more years of
      education, and lower frequency and severity of psychotic-type symptoms were
      associated with a greater likelihood of favorable productivity outcome.
      CONCLUSIONS: We identified risk factors for the occurrence of psychotic-type
      symptoms and extended previous findings regarding the significance of these
      symptoms for outcome after TBI. These findings suggest that improved sleep in
      early TBI recovery may decrease the occurrence of psychotic-type symptoms.

PMID- 23535391
TI  - Application and clinical utility of the Glasgow Coma Scale over time: a study
      employing the NIDRR traumatic brain injury model systems database.
AB  - OBJECTIVE: To examine possible changes in Glasgow Coma Scale (GCS) scores related
      to changes in emergency management, such as intubation and chemical paralysis,
      and the potential impact on outcome prediction. PARTICIPANTS: 10 228 patients
      from the Traumatic Brain Injury Model Systems national database. DESIGN:
      Retrospective study examining 5-year epochs from 1987 to 2012. MAIN MEASURES: GCS
      score assessed in the Emergency Department (GCS scores for intubated, but not
      paralyzed, patients were estimated with a formula using 2 of the 3 GCS
      components), Outcome: Functional Independence Measure (FIM) assessed at
      rehabilitation admission. RESULTS: The rate of intubation prior to GCS scoring
      averaged 43% and did not increase across time. However, a clear increase over
      time was observed in the use of paralytics or heavy sedatives, with 27% of
      patients receiving this intervention in the most recent epoch. Estimated GCS
      scores classified 69% of intubated patients as severely brain injured and 8% as
      mildly injured. The GCS accounted for a modest, yet consistent, amount of
      variability (approximately 5%-7%) in FIM scores during most epochs. CONCLUSIONS:
      Given the frequency of intubation and/or paralysis following brain injury in this
      sample, estimating GCS or exploring other means to gauge injury severity is
      beneficial, particularly because a portion likely did not sustain severe brain
      injury. There is no evidence for declining predictive utility of the GCS over
      time.

PMID- 23535392
TI  - Inpatient cognitive rehabilitation: is it time for a change?

PMID- 23535393
TI  - Evidence of anti-proliferative activities in blue mussel (Mytilus edulis) by
      products.
AB  - Shellfish waste components contain significant levels of high quality protein and
      are therefore a potential source for biofunctional high-value peptides. The
      feasibility of applying a pilot scale enzymatic hydrolysis process to whole
      Mytilus edulis and, by fractionation, recover hydrolysates presenting a
      biological activity of interest, was evaluated. Fractions were tested on four
      immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa
      fraction, enriched in peptides, presented anti-proliferative activity with all
      cell lines and results suggest a bioactive molecule synergy within the fraction.
      At a protein concentration of 44 ug/mL, the 50 kDa fraction induced a mortality
      of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At
      the low protein concentration of only 11 ug/mL the 50 kDa fraction still entails
      a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction
      contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis
      and the lowest levels detected of taurine and methionine and highest levels of
      threonine, proline and glycine amino acids. The enzymatic hydrolysis process
      suggests that Mytilus edulis by-products should be viewed as high-valued products
      with strong potential as anti-proliferative agent and promising active
      ingredients in functional foods.

PMID- 23535395
TI  - Effect of Siam weed extract and its bioactive component scutellarein tetramethyl
      ether on anti-inflammatory activity through NF-kappaB pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Siam weed (Chromolaena odorata (L.) King and
      Robinson) is a medicinal herb used for wound healing and inflammation-related
      diseases. AIM OF THE STUDY: In this study, we evaluated the molecular mechanism
      by which Siam weed extract (SWE) and its bioactive components, scutellarein
      tetramethyl ether (scu), stigmasterol, and isosakuranetin affect anti
      inflammatory activity. MATERIALS AND METHODS: The expression of several
      inflammatory proteins in RAW 264.7 (murine) macrophages was assessed by Western
      blot and reverse transcription-polymerase chain reaction (RT-PCR). Biochemical
      assays including prostaglandin E2 (PGE2) and nitric-oxide (NO) quantification
      were performed. Luciferase promoter activity and immunocytochemistry of Nuclear
      factor-kappaB (NF-kappaB) were investigated. RESULTS: Cyclooxygenase-2 (COX-2)
      and inducible nitric oxide synthase (iNOS) are critical pro-inflammatory
      proteins. The level of protein and mRNA expression of these enzymes induced by
      lipopolysaccharide (LPS) was dramatically suppressed by treatment with SWE, scu,
      or stigmasterol compounds in a dose-dependent manner. They also reduced PGE2 and
      NO release. We further analyzed the NF-kappaB pathway and found that the scu
      compound suppressed IkappaB kinase complex alpha/beta (IKKalpha/beta) and
      Inhibitory-kappa-B-alpha (IkappaBalpha), thereby suppressing COX-2 and iNOS
      expression. CONCLUSION: This is the first report of the anti-inflammatory
      molecular mechanism in SWE and/or its bioactive component scu, indicating
      alteration NF-kappaB pathway and further providing potential uses in the
      treatment of inflammatory-related diseases.

PMID- 23535396
TI  - Can intermediate-frequency magnetic fields affect memory function-related gene
      expressions in hippocampus of C57BL/6J mice?
AB  - Recently, a cooking appliance based on the principle of electromagnetic induction
      has come to be used domestically on a widespread basis; this induction heating
      cooking hob mainly generates intermediate-frequency magnetic fields (IF-MF).
      However, whether electromagnetic fields originating from household appliances
      represent a health risk remains uncertain. We investigated the effect of IF-MF on
      the expressions of memory function-related genes and related transduction
      molecules in the mouse hippocampus. Male and female C57BL/6J mice were allotted
      to a control (sham-exposed), an exposure, or a recovery (one week after exposure)
      group and were exposed to IF-MF (21 kHz, 3.8 mT) one hour per day for 2 weeks.
      Twenty-four hour after final exposure, the expression levels of memory function
      related genes and the mRNA levels for signal transduction pathway molecules in
      the hippocampi were examined using real-time RT-PCR. The relative mRNA expression
      levels of the N-methyl-D aspartate (NMDA) receptor subunits NR1, NR2A, and NR2B
      as well as transcription factors (calcium/calmodulin-dependent protein kinase
      (CaMK) -IV, cyclic AMP responsive element binding protein (CREB) -1) and
      neurotrophins (nerve growth factor (NGF), and brain-derived neurotrophic factors
      (BDNF)) were not significantly altered in the IF-MF-exposed mice. We also
      examined the morphology of the hippocampus using a histological analysis, but no
      changes in the IF-MF-exposed mice were seen. This is the first in vivo study to
      show that IF-MF exposure did not affect the expression levels of memory function
      related genes in the hippocampus of C57BL/6J mice. The present findings suggest
      that IF-MF exposure may not affect cognitive function in the present animal
      model.

PMID- 23535397
TI  - Combined repeated dose and reproductive/developmental toxicity screening test of
      tert-butylhydrazine monohydrochloride in rats.
AB  - tert-Butylhydrazine monohydrochloride was daily administered by gavage to groups
      of Crl:CD (SD)IGS rats at doses of 0 (control), 0.8, 4, or 20 mg/kg/day. Twelve
      males per group were treated for a total of 42 days from 14 days before mating.
      Twelve females per group were treated from 14 days before mating to day 4 of
      lactation throughout the mating and gestation periods. Recovery groups of five
      males and five non-pregnant females per group were dosed for 42 days followed by
      a 14-day recovery period. No deaths were observed in any groups of either sex.
      There were no considerable changes in body weight, food intake, general
      appearance, functional observations or biochemical analysis. Values of the anemic
      parameters were decreased in the 20 mg/kg/day males and in all female dose
      groups. The relative weight of the liver, kidneys and spleen was significantly
      increased in 20 mg/kg/day females. Histopathological examination showed
      congestion and hemosiderin deposition in the spleen at 20 mg/kg/day in both
      sexes, but there were no changes in the liver or kidneys in either sex. Anemic
      parameters with hemosiderin deposition did not completely recover in the 20
      mg/kg/day group in both sexes after the recovery period. As for reproduction, a
      significant reduction was only observed in the number of corpora lutea at 20
      mg/kg/day. It was thus concluded that the LOAEL was 0.8 mg/kg/day based on the
      decreased values of the anemic parameters of repeated-dose toxicity, and that the
      NOAEL was 4 mg/kg/day based on the low number of corpora lutea of
      reproductive/developmental toxicity.

PMID- 23535394
TI  - An overview on the marine neurotoxin, saxitoxin: genetics, molecular targets,
      methods of detection and ecological functions.
AB  - Marine neurotoxins are natural products produced by phytoplankton and select
      species of invertebrates and fish. These compounds interact with voltage-gated
      sodium, potassium and calcium channels and modulate the flux of these ions into
      various cell types. This review provides a summary of marine neurotoxins,
      including their structures, molecular targets and pharmacologies. Saxitoxin and
      its derivatives, collectively referred to as paralytic shellfish toxins (PSTs),
      are unique among neurotoxins in that they are found in both marine and freshwater
      environments by organisms inhabiting two kingdoms of life. Prokaryotic
      cyanobacteria are responsible for PST production in freshwater systems, while
      eukaryotic dinoflagellates are the main producers in marine waters.
      Bioaccumulation by filter-feeding bivalves and fish and subsequent transfer
      through the food web results in the potentially fatal human illnesses, paralytic
      shellfish poisoning and saxitoxin pufferfish poisoning. These illnesses are a
      result of saxitoxin's ability to bind to the voltage-gated sodium channel,
      blocking the passage of nerve impulses and leading to death via respiratory
      paralysis. Recent advances in saxitoxin research are discussed, including the
      molecular biology of toxin synthesis, new protein targets, association with metal
      binding motifs and methods of detection. The eco-evolutionary role(s) PSTs may
      serve for phytoplankton species that produce them are also discussed.

PMID- 23535398
TI  - Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase
      inhibition without cell death after chlorpyrifos administration.
AB  - Organophosphates (OPs) are important toxic compounds commonly used for a variety
      of purposes in agriculture, industry and household settings. It has been well
      established that the main mechanism of acute toxic action of OP is the inhibition
      of acetylcholinesterase (AChE). However, we observed long term deficit after
      acute subcutaneous exposure to Chlorpyrifos (CPF) even when AChE activity is
      restored. In fact, besides AChE inhibition, non-AChE targets have also been
      proposed as an alternative mechanism involved in the acute lethal action and side
      effects of short or long-term exposure. In this context, our main aim in this
      research was to establish a dose-response curve of Acylpeptide hydrolase (APH)
      and AChE regional brain activity after acute CPF administration that could
      explain these long term effects observed in the literature. Moreover, since
      available data suggest that long term effects of OPs exposure could involve
      neuronal cell death, our second aim was to evaluate, assessing by Fluoro-Jade B
      (FJB) staining, whether CPF produces induced cell death. Our results show that an
      acute exposure to 250 mg/kg CPF does not induce neuronal death as measured by FJB
      but produces highest AChE regional brain inhibition after administration. In
      addition, APH seems to be more sensitive than AChE to CPF exposure because after
      31 days of exposure, complete recovery was seen only for APH activity at Frontal
      Cortex, Cerebellum and Brain Stem.

PMID- 23535399
TI  - Simulation of acute reference dose (ARfD) settings for pesticides in Japan.
AB  - In order to develop guidelines for setting acute reference doses (ARfDs) for
      pesticides in Japan, we conducted simulations of ARfD settings based on
      evaluation reports for 201 pesticides assessed by the Food Safety Commission
      (FSC) in Japan over the last 8 years. Our conceptual principles were based on the
      concepts written by Solecki et al. (2005) and were adapted for toxicological data
      required in Japan. Through this process, we were able to set the ARfDs for over
      90% of the 201 pesticides tested. The studies that provided the rationale for
      ARfD setting were primarily reproductive and developmental toxicity studies,
      acute neurotoxicity studies, and pharmacology studies. For approximately 30% of
      the pesticides simulated in the present study, it was not necessary to establish
      ARfDs. Some of the simulated ARfDs resulting from their endpoints may be
      conservative estimates, because the evaluation reports were written for
      acceptable daily intake settings. Thus, it was sometimes difficult to distinguish
      acute toxic alerts from repeated toxicities. We were unable to set an ARfD for 14
      pesticides because of insufficient data on acute toxicities. This could be
      improved by more complete recordkeeping. Furthermore, we categorized the 201
      pesticides by mechanism of action or chemical structure. Our simulation indicates
      that the conceptual framework presented here can be used as a basis for the
      development of guidelines on ARfD settings for pesticides in Japan.

PMID- 23535400
TI  - Photodegradation of pharmaceuticals in the aquatic environment by sunlight and UV
      A, -B and -C irradiation.
AB  - In order to investigate the effect of sunlight on the persistence and ecotoxicity
      of pharmaceuticals contaminating the aquatic environment, we exposed nine
      pharmaceuticals (acetaminophen (AA), amiodarone (AM), dapsone (DP), dexamethasone
      (DX), indomethacin (IM), naproxen (NP), phenytoin (PH), raloxifene (RL), and
      sulindac (SL)) in aqueous media to sunlight and to ultraviolet (UV) irradiation
      at 254, 302 or 365 nm (UV-C, UV-B or UV-A, respectively). Degradation of the
      pharmaceuticals was monitored by means of high-performance liquid chromatography
      (HPLC). Sunlight completely degraded AM, DP and DX within 6 hr, and partly
      degraded the other pharmaceuticals, except AA and PH, which were not degraded.
      Similar results were obtained with UV-B, while UV-A was less effective (both UV-A
      and -B are components of sunlight). All the pharmaceuticals were photodegraded by
      UV-C, which is used for sterilization in sewage treatment plants. Thus, the
      photodegradation rates of pharmaceuticals are dependent on both chemical
      structure and the wavelength of UV exposure. Toxicity assay using the luminescent
      bacteria test (ISO11348) indicated that UV irradiation reduced the toxicity of
      some pharmaceuticals to aquatic organisms by decreasing their amount
      (photodegradation) and increased the toxicity of others by generating toxic
      photoproduct(s). These results indicate the importance of investigating not only
      parent compounds, but also photoproducts in the risk assessment of
      pharmaceuticals in aquatic environments.

PMID- 23535401
TI  - Crotonaldehyde induces apoptosis in alveolar macrophages through intracellular
      calcium, mitochondria and p53 signaling pathways.
AB  - Crotonaldehyde, a highly electrophilic alpha, beta-unsaturated aldehyde, is a
      ubiquitous environmental pollutant and a risk factor for multiple respiratory
      diseases. Crotonaldehyde is highly volatile and hydrophilic, so it is efficiently
      absorbed in the respiratory tract. Alveolar macrophages are major effector cells
      of the nonspecific host defence in the lung. The aim of this study was to
      investigate the molecular mechanisms and signaling pathways responsible for cell
      death of alveolar macrophage induced by crotonaldehyde. Our results show that
      crotonaldehyde induces apoptosis in alveolar macrophages, as indicated by
      phosphatidylserine externalization and DNA fragmentation. Pretreatment of
      alveolar macrophages with N-acetylcysteine, ascorbic acid, alpha-tocopherol,
      superoxide dismutase inhibited crotonaldehyde-induced apoptosis. Crotonaldehyde
      induced apoptosis was characterized by ROS generation, GSH depletion, loss of
      mitochondrial membrane potential (DeltaPsim), the release of cytochrome c from
      mitochondria, caspase-3/7 and caspase-9 activation, elevation of intracellular
      Ca(2+) concentration and the increase of p53 expression. Furthermore,
      pretreatment with either p53 inhibitor pifithrin-alpha or calcium chelator BAPTA
      AM effectively attenuated apoptosis induced by crotonaldehyde. Taken together,
      our results showed that crotonaldehyde induce apoptosis in alveolar macrophages
      through intracellular calcium, mitochondria and p53 signaling pathways. These
      results would help to illustrate the mechanism of toxicity induced by
      crotonaldehyde and to look for a novel treatment for diseases induced by exposure
      to crotonaldehyde-rich pollutants such as cigarette smoke.

PMID- 23535402
TI  - Genotoxicity evaluation of chlorpyrifos: a gender related approach in regular
      toxicity testing.
AB  - The oral intubation of chlorpyrifos, an extensively used organophosphate
      insecticide, was tested for its capability to induce in vivo genotoxic upshot in
      blood lymphocytes of 24 male and female Wistar rats using biomarker of
      genotoxicity. Rats were orally administered with daily doses 3 and 12 mg/kg body
      weight (BW) of chlorpyrifos (CPF). The blood lymphocytes were harvested after 7
      and 14 days of treatment and subjected to bi-nucleus (BN), multi-nucleus (MN) and
      single cell gel electrophoresis (comet assay) to evaluate the extent of DNA
      damage. Other than BN and MN assay, damage to DNA was assessed through comet
      length, height, area, head diameter, head DNA percentage and tail DNA percentage
      along with tail movement. A significant boost was noticed in the frequency of BN
      cells formation after 12 mg/kg BW CPF treatment. However, the propensity to
      produce MN cells was significantly more (P <= 0.05) in males than that of
      females. Likewise, the frequency of comet formation, mean comet length, height
      and area were more (P <= 0.05) in males than females even with 12 mg/kgBW. Comet
      head DNA % and tail length remained non-significant. Olive movement also revealed
      a significant increase (P <= 0.05) in males than females. The study inferred that
      the CPF can induce DNA damage in both male and female subjects but more
      pronounced in the male individuals.

PMID- 23535403
TI  - Fetal exposure to diesel exhaust affects X-chromosome inactivation factor
      expression in mice.
AB  - Several studies have shown effects of diesel exhaust (DE) on the central nervous
      system, but the mechanism is unclear. Fetal mice were exposed to whole DE
      (contains gases and particles) in an inhalation chamber, and cerebrum gene
      expression changes were examined by gene assay (microarray and quantitative real
      time PCR). By microarray, upregulation of Xist, B-raf and Drwms2 were detected.
      Especially, mRNA expression of Xist was increased in a concentration-dependent
      manner in male and female mice. Xist (X-inactive specific transcript) is a major
      effector of the X-inactivation process, and X-linked genes are highly expressed
      in brain tissue and consistent with a role in brain developments. By quantitative
      real-time PCR, Tsix (crucial noncoding antisense partner of Xist) and other X
      linked genes (Mecp2, Hprt1, and Sts) were examined; Tsix was upregulated, and
      other X-linked genes were unaffected in the male and female mice. Our findings
      suggest that exposure to DE increases Xist and Tsix gene expression in utero
      without influencing X-linked gene expression. An examination of Xist gene
      expression changes may provide an important biomarker for DE-induced effects. The
      possibility of avoiding X-chromosome inactivation (XCI) mechanisms by minimizing
      exposure to DE is expected.

PMID- 23535404
TI  - Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L
      LTP of hippocampus in rats.
AB  - Epidemiological investigations have indicated that aluminum (Al), as an important
      environmental neurotoxicant, could cause damage to the cognitive function which
      was closely related with neurodegenerative diseases. Long-term potentiation (LTP)
      is one form of synaptic plasticity in association with cognitive function.
      Previous studies have demonstrated that Al impaired early phase long-term
      potentiation (E-LTP) in vivo and in vitro. However, Al-induced damage to late
      phase long-term potentiation (L-LTP) has poorly been studied. The present study
      was designed to observe the effects of subchronic Al exposure on the spatial
      memory, hippocampus ultrastructure and L-LTP in rats. Pregnant Wistar rats were
      assigned to four groups. Neonatal rats were exposed to Al by parental lactation
      from parturition to weaning for 3 weeks and then fed with the distilled water
      containing 0, 0.2%, 0.4% and 0.6% aluminum chloride (AlCl3) respectively from
      weaning to postnatal 3 months. The levels of Al in blood and hippocampus were
      quantitated by atomic absorption spectrophotometer. Morris water maze test was
      performed to study spatial memory. The induction and maintenance of L-LTP in area
      of Schaffer collateral- CA1 synapse was recorded by extracellular microelectrode
      recording technology in hippocampus of experimental rats. Hippocampus was
      collected for transmission electron microscopy observation. The results showed
      that the Al concentrations in blood and hippocampus of Al-exposed rats were
      higher than those of the control rats. Al could impair spatial memory ability of
      rats. Neuronal and synaptic ultrastructure from Al-exposed rats presented
      pathological changes; the incidence of L-LTP has a decrease trend while
      population spike (PS) amplitude was much smaller significantly stimulated by high
      frequency stimulation (HFS) in Al-exposed rats. Our findings showed that Al
      exposure caused spatial memory damage, under which the neuronal and synaptic
      ultrastructure changes maybe were their morphological basis and the impaired L
      LTP of hippocampus could be their electrophysiological basis.

PMID- 23535405
TI  - Neutrophil gelatinase-associated lipocalin, a sensitive urinary biomarker of
      acute kidney injury in dogs receiving gentamicin.
AB  - A sensitive urinary biomarker for acute kidney injury (AKI) was investigated in
      beagle dogs with nephrotoxicity induced by gentamicin. Gentamicin sulphate at 25
      or 50 mg/kg was injected (s.c.) for 9 days, and conventional urinalysis, ELISA
      assay of neutrophil gelatinase-associated lipocal (NGAL) in urine, blood
      chemistry, and pathological examinations were performed. The dog given gentamicin
      at 25 mg/kg only showed slight deposition of lysosomal granules in the proximal
      tubular epithelium of the kidneys without any other significant changes even
      though urinary NGAL was elevated on Day 10 (day of necropsy). In the dog
      receiving gentamicin at 50 mg/kg, increases in urinary NGAL were observed on Days
      3 and 5, and absence of urination, marked increases in serum urea nitrogen and
      creatinine, enlargement and discoloration of the kidneys with marked necrosis,
      and swelling of proximal epithelium were observed. In conclusion, urinary NGAL is
      considered to be a candidate as a sensitive predictable biomarker of AKI in the
      gentamicin-induced nephrotoxicity model in dogs.

PMID- 23535406
TI  - Neonatal exposure to 2,3,7,8-tetrachlorodibenze-p-dioxin increases the mRNA
      expression of prostatic proteins in C57BL mice.
AB  - The effects of neonatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) on prostatic secretory protein expression were investigated. Male
      C57BL mice were treated with TCDD at 10, 100, or 1,000 ng/kg body weight at
      postnatal day (PND) 6. At PND42, the ventral, dorsolateral, and anterior
      prostatic lobes were dissected and the mRNA expression of prostatic proteins
      including spermine-binding protein, serine protease inhibitor Kazal type 3,
      prostate secretory protein 94 (PSP94), immunoglobulin binding protein-like
      protein (IgGBPLP), experimental autoimmune prostatitis antigen proteins, and
      peroxiredoxin-6 (Prdx6) was measured by quantitative PCR. There was no
      significant difference in the weight of the prostatic lobes between the control
      and TCDD-treated groups. The expression of PSP94 and Prdx6 in the ventral
      prostate and IgGBPLP in the dorsolateral prostate at PND42 was significantly
      increased by neonatal TCDD treatment in a dose-dependent manner, while no changes
      were noted in other prostatic secretions. These data suggest that neonatal
      exposure to TCDD may have effects on the neonatal differentiation of the prostate
      and results in the hyper-expression of some prostatic proteins later in life.

PMID- 23535407
TI  - Gene expression of epigenetic regulatory factors related to primary silencing
      mechanism is less susceptible to lower doses of bisphenol A in embryonic
      hypothalamic cells.
AB  - DNA methyltransferases (DNMTs) are associated with epigenetic regulation of gene
      expression, and methyl-CpG binding protein 2 (MECP2) acts as a long-range
      regulator of methylated genes. We evaluated the effects of bisphenol A (BPA) on
      embryonic mouse hypothalamic cells, with particular emphasis on the gene
      expression of Dnmts (Dnmt1, Dnmt3a, and Dnmt3b) and Mecp2 isoforms. In a dose
      dependent (0.02-200 uM BPA) 3-hr experiment, real-time reverse transcription
      polymerase chain reaction revealed that gene expression of both Dnmts and
      Mecp2_e2 was affected at 200 uM and that of Mecp2_e1 was affected at > 20 uM.
      These results suggest that gene expression of Dnmts and Mecp2 are less
      susceptible to lower doses of BPA in developing hypothalamic cells. However, as
      BPA concentration increases, this agent has the potential to alter gene
      expression of key players that provide stability and flexibility of epigenetic
      gene regulation, which could disrupt the normal development of hypothalamic
      functions.

PMID- 23535408
TI  - New parameter that supports speculation on the possible mechanism of
      hypothyroidism induced by chemical substances in repeated-dose toxicity studies.
AB  - Hypothyroidism induced by xenobiotic treatment was analyzed for possible
      underlying mechanism(s) on the basis of different responses of the thyroid gland
      and the liver, using a newly-created database of repeated-dose toxicity of 500
      chemicals. Two mechanisms are proposed: direct inhibition of thyroid hormone
      biosynthesis in the thyroid gland, and stimulated degradation of thyroid hormone
      by induction of hepatic drug-metabolizing enzymes. In the database there were 10
      chemicals inducing hypertrophy/hyperplasia of follicular cells in the thyroid
      gland and having data on thyroid glands. On the basis of the chemical structure
      and information available in the literature, we judged three chemicals to be
      typical thioamide derivatives that act directly on the thyroid gland, and the
      others as non-thioamide derivatives that were unlikely to have any direct action
      on the thyroid gland. All these chemicals were classified into two groups using
      the ratios of relative weight increase rate of thyroid gland versus that of the
      liver. These values were at least 1.7, but 3.2 or more in the most of the cases
      for thioamide derivatives, and 1.2 or less for non-thioamide derivatives. This
      background analysis suggests the feasibility of parameter-supported speculation
      on the possible underlying mechanism when new repeated-dose toxicity data on
      hypothyroidism becomes available.

PMID- 23535409
TI  - Deletion of the ubiquitin-conjugating enzyme Ubc2 confers resistance to
      methylmercury in budding yeast by promoting Whi2 degradation.
AB  - Ubiquitin-conjugating enzymes involved in sensitivity to methylmercury in yeast
      were identified by deletion analysis, which showed that Ubc2- or Ubp13-deficiency
      conferred resistance to methylmercury. Whi2, which was previously shown to be
      associated with increased methylmercury toxicity and is intracellularly degraded
      via the ubiquitin-proteasome system, was expressed at significantly lower levels
      in Ubc2-deficient yeast than in wild-type yeast. Ubc2/Whi2 double-deficient yeast
      showed neither an additive nor synergistic increase in methylmercury resistance.
      Our results indicate that Ubc2 may increase the sensitivity to methylmercury in
      yeast by inhibiting the proteasomal degradation of Whi2.

PMID- 23535410
TI  - Induction of the fatty acid 2-hydroxylase (FA2H) gene by Delta(9)
      tetrahydrocannabinol in human breast cancer cells.
AB  - To investigate gene(s) being regulated by ?(9)-tetrahydrocannabinol (?(9)-THC),
      we performed DNA microarray analysis of human breast cancer MDA-MB-231 cells,
      which are poorly differentiated breast cancer cells, treated with ?(9)-THC for 48
      hr at an IC50 concentration of approximately 25 uM. Among the highly up-regulated
      genes (> 10-fold) observed, fatty acid 2-hydroxylase (FA2H) was significantly
      induced (17.8-fold). Although the physiological role of FA2H has not yet been
      fully understood, FA2H has been shown to modulate cell differentiation. The
      results of Oil Red O staining after ?(9)-THC exposure showed the distribution of
      lipid droplets (a sign of the differentiated phenotype) in cells. Taken together,
      the results obtained here indicate that FA2H is a novel ?(9)-THC-regulated gene,
      and that ?(9)-THC induces differentiation signal(s) in poorly differentiated MDA
      MB-231 cells.

PMID- 23535411
TI  - Healing environments for everyone: Facilities that don't consider staff miss the
      point.

PMID- 23535412
TI  - An insider's view on fall prevention: an NP with a history of falls argues that
      we can do better.

PMID- 23535413
TI  - Men and nursing.

PMID- 23535414
TI  - Hope in hospice.

PMID- 23535415
TI  - Hope in hospice.

PMID- 23535416
TI  - Hope in hospice.

PMID- 23535417
TI  - Hope in hospice.

PMID- 23535418
TI  - One voice.

PMID- 23535419
TI  - Evidence-based practice.

PMID- 23535420
TI  - New Jersey superior court upholds joint protocol for APN/As: New state senate and
      house bills could eliminate that requirement.

PMID- 23535421
TI  - NICUs lack privacy for pumping breast milk: and even when mothers have privacy,
      they prefer pumping at home.

PMID- 23535423
TI  - Making a list and saving a life: checklists reduce the failure rate of lifesaving
      procedures during operating room crises.

PMID- 23535426
TI  - Computerization in nursing handoffs: face-to-face handoffs are still valuable;
      bedside handoffs, less so.

PMID- 23535427
TI  - Suicidal behavior remains common even in treated teens: at least one mental
      disorder usually precedes suicidal behaviors.

PMID- 23535431
TI  - From disparity to equity: racial and ethnic health disparities persist, but
      nursing is providing several solutions.

PMID- 23535432
TI  - Update on the Patient Protection and Affordable Care Act: milestones and
      challenges in implementing the ACA.

PMID- 23535439
TI  - Greening the 'proclamation for change': healing through sustainable health care
      environments: nurses advocate sustainable design to transform health care.

PMID- 23535440
TI  - Fresh air and sunshine.

PMID- 23535441
TI  - Where's the 'health' in mental health? We lack balance in our current approach to
      mental health care.

PMID- 23535442
TI  - 'Crucial conversations' in the workplace: offering nurses a framework for
      discussing-and resolving- incidents of lateral violence.

PMID- 23535443
TI  - A smart doctor listens to the nurses.
AB  - A pediatrician pays tribute to her mother's career.

PMID- 23535444
TI  - In vivo effects of foam sclerotherapy on coagulation.
AB  - OBJECTIVE: The aim of this study was to evaluate whether foam sclerotherapy (FS)
      induces changes in CAT (calibrated automated thrombinography) and other
      coagulation parameters which could indicate an increased risk of thrombotic
      events. METHODS: Blood samples from eight patients treated with FS were taken
      before treatment and 30 minutes, one and four hours and one week after treatment.
      CAT parameters (ETP1n, Peak1n, Lag time 1), thrombin antithrombin complexes
      (TAT), d-dimers, fibrinogen, Von Willebrand (vWf Ag) factor and platelet-derived
      microparticles (MIPAs) were measured. RESULTS: Significant changes over time for
      Peak1n, fibrinogen, d-dimers, vWfAg and TAT complexes were observed. CAT
      parameters decreased over time, except for Lag time 1. D-dimers and TAT complexes
      increased and fibrinogen, vWf Ag, MIPA's decreased during the first hours.
      CONCLUSION: The findings in this study support the hypothesis that FS initiate
      coagulation pathways, but there is no evidence that this activation results in an
      increased thrombosis risk.

PMID- 23535445
TI  - Electrical induction of vision.
AB  - We assess what monkeys see during electrical stimulation of primary visual cortex
      (area V1) and relate the findings to visual percepts evoked electrically from
      human V1. Discussed are: (1) the electrical, cytoarchitectonic, and visuo
      behavioural factors that affect the ability of monkeys to detect currents in V1;
      (2) the methods used to ascertain what monkeys see when electrical stimulation is
      delivered to V1; (3) a corticofugal mechanism for the induction of visual
      percepts; and (4) the quantity of information transferred to V1 by electrical
      stimulation. Experiments are proposed that should advance our understanding of
      how electrical stimulation affects macaque and human V1. This work contributes to
      the development of a cortical visual prosthesis for the blind. We dedicate this
      work to the late Robert W. Doty.

PMID- 23535446
TI  - Early neurodevelopmental assessment in Duchenne muscular dystrophy.
AB  - The aim of this study was to assess neurodevelopmental profile in young boys
      affected by Duchenne muscular dystrophy and to establish the correlation between
      neurodevelopmental findings, and the type and site of mutations. A structured
      neurodevelopmental assessment (Griffiths Scale of Mental Development) was
      performed in 81 DMD boys before the age of four years (range: 7-47 months). The
      mean total DQ was 87 (SD 15.3). Borderline DQ (between 70 and 84) was found in
      32% and DQ below 70 in 12.3% of the patients. Children with mutations upstream or
      in exon 44 had higher DQ than those with mutations downstream exon 44 which are
      associated with involvement of dystrophin isoforms expressed at high levels in
      brain. The difference was significant for total and individual subscale DQ with
      the exception of the locomotor subscale. Items, such as ability to run fast, or
      getting up from the floor consistently failed in all children, irrespective of
      the age or of the site of mutation. Our results help to understand the possible
      different mechanisms underlying the various aspects of neurodevelopmental delay,
      suggesting that the involvement of brain dystrophin isoforms may cause a delay in
      the maturation of coordination and dexterity.

PMID- 23535447
TI  - Impact of electrocardiographic findings for diagnosis of left ventricular
      hypertrophy in patients with primary aldosteronism.
AB  - BACKGROUND: Compared to patients with similar levels of hypertension, patients
      with primary aldosteronism have a greater left ventricular hypertrophy (LVH). The
      presence of LVH should be detected as early as possible to prevent cardiovascular
      complications associated with the condition. We evaluated comparative diagnostic
      value of electrocardiographic (ECG) indexes for LVH in patients with primary
      aldosteronism. METHODS: ECG and echocardiographic data were obtained in 88
      patients with primary aldosteronism. We analyzed the four most commonly used ECG
      indexes, including Sokolow-Lyon index, Cornell voltage index, Cornell product
      index, and Gubner index. RESULTS: Echocardiographic LVH was found in 35 patients
      (40%). Sensitivity ranged from 0% for Gubner index to 49% for Cornell product
      index. Specificity ranged from 81% for Sokolow-Lyon index to 100% for Gubner
      index. Sokolow-Lyon index (r=0.43, p<0.001), Cornell voltage index (r=0.55,
      p<0.001) and Cornell product index (r=0.52, p<0.001) correlated significantly
      with left ventricular mass (LVM) index. No significant correlation was found
      between Gubner index and LVM index. CONCLUSIONS: ECG indexes had a reasonably
      high specificity, but a low sensitivity for LVH in patients with primary
      aldosteronism. Cornell voltage index and Cornell product index had a better
      diagnostic value of LVH, and had a better correlation with LVM index in these
      patients.

PMID- 23535449
TI  - Establishment of auditory discrimination and detection of tinnitus induced by
      salicylic acid and intense tone exposure in the rat.
AB  - Rats were trained in a two lever food reinforced operant procedure to
      discriminate a 8000 Hz pure tone stimulus from its absence. Responding on one
      lever was reinforced in the presence of the tone and responding on the other
      lever was reinforced when the tone was absent. Frequency generalization testing
      yielded an inverted U-shaped function, whereas sound pressure level
      generalization testing yielded a continuous decrease in responding on the tone
      associated lever with decreasing sound pressure levels. The administration of
      sodium salicylic acid (150-450 mg/kg) generated responding on the tone associated
      lever suggesting that salicylic acid induced an experience that had commonalities
      with the percept of the training tone stimulus. After exposure to intense sound,
      responding consistent with the presence of tinnitus was achieved and Lidocaine
      failed to reduce tinnitus behavior. The use of a two choice design helped avoid
      confounding factors induced by drug induced side effects. Further, since no
      auditory cues were employed in the test situation the model achieves resistance
      to potential bias due to hearing impairment and hyperacusis. We propose that this
      model may be useful in detecting tinnitus.

PMID- 23535450
TI  - Frequency of reported European ancestry among multiple sclerosis patients from
      four cities in the southern and southeastern regions of Brazil.
AB  - Recent reports on the prevalence of multiple sclerosis (MS) have described
      discrepancies between the rates in cities in the northeastern and southeastern
      regions of Brazil, representing a north-south gradient. European immigrants
      settled in southeastern and southern Brazil at the beginning of the twentieth
      century. In this study, we report the frequency of European ancestors among
      Brazilian MS patients in four cities in the southern and southeastern regions of
      Brazil. METHODS: A total of 652 consecutive patients with confirmed MS diagnoses
      seen at four centers in Belo Horizonte, Ribeirao Preto, Londrina and Santos were
      asked about the origin of their ancestors, going back three generations. RESULTS:
      287 (44%) reported Italian ancestry, 211 (32%) reported that all ancestors were
      born in Brazil, 49 (7.5%) had Portuguese ancestry and 70 (10%) had Spanish
      ancestry. The patients in Belo Horizonte and Londrina reported higher proportions
      of Italian ancestry than the proportions estimated for the populations of their
      respective States. CONCLUSION: Brazil has a north-south gradient of 0.91/100,000
      per degree of latitude, which is higher than the gradient for Latin America.
      Since the largest immigrant group that settled in southern and southeastern
      Brazil was from Italy, it is possible that Italian immigration was one of the
      factors that have contributed toward increasing the prevalence of MS in these
      regions.

PMID- 23535448
TI  - A selective membrane estrogen receptor agonist maintains autonomic functions in
      hypoestrogenic states.
AB  - It is well known that many of the actions of estrogens in the central nervous
      system are mediated via intracellular receptor/transcription factors that
      interact with steroid response elements on target genes. But there is also a
      compelling evidence for the involvement of membrane estrogen receptors in
      hypothalamic and other CNS functions. However, it is not well understood how
      estrogens signal via membrane receptors, and how these signals impact not only
      membrane excitability but also gene transcription in neurons. Indeed, it has been
      known for sometime that estrogens can rapidly alter neuronal activity within
      seconds, indicating that some cellular effects can occur via membrane delimited
      events. In addition, estrogens can affect second messenger systems including
      calcium mobilization and a plethora of kinases within neurons to alter cellular
      functions. Therefore, this brief review will summarize our current understanding
      of rapid membrane-initiated and intracellular signaling by estrogens in the
      hypothalamus, the nature of receptors involved and how these receptors contribute
      to maintenance of homeostatic functions, many of which go awry in menopausal
      states. This article is part of a Special Issue entitled Hormone Therapy.

PMID- 23535451
TI  - A game of viral hide and seek: miliary PML masquerading as EBV encephalitis in an
      HIV+ patient.

PMID- 23535452
TI  - Evaluating alternative forest management strategies for the Champagne and
      Aishihik Traditional Territory, southwest Yukon.
AB  - Sustainable forest management (SFM) requires the balancing of diverse values and
      conflicting management objectives. Climate change adds a further degree of
      uncertainty to this complex issue. In this study we analysed a Strategic Forest
      Management Plan (SFMP) from the southwest Yukon, Canada. The SFMP was developed
      to enable the salvage harvesting of beetle-killed white spruce stands and
      encourage fuel-abatement treatments to reduce fire risk to local communities. It
      did not, however, provide a long-term strategy to achieve SFM in the region. In
      this study, the SFMP served as the basis to develop and evaluate alternative
      forest management strategies in the context of climate change. Working group
      discussions with local stakeholders enabled the structuring of a ratings table
      that helped practitioners and experts to characterize five alternative strategies
      stemming from the SFMP, based on its main goals and objectives. An Analytic
      Hierarchy Process (AHP) was then used to balance competing values and objectives
      and test the alternatives against each other. The strategy 'Manage for multiple
      values and use' had the highest AHP-score when compared to the four other
      alternatives (timber, wildlife, fire risk reduction and carbon), which were
      narrower in scope. It may represent the best balance for the ecological and socio
      economic values listed in the SFMP. Although the multiple values (MV) alternative
      is closest to the current SFMP in terms of scope, this study highlights that
      there are viable alternatives such as 'manage for wildlife' that achieved similar
      scores to the MV approach. The current SFMP has great potential to serve as a
      basis and starting point for a continuous and adaptive planning process for
      forest management. Exploring the different/alternative strategic directions will
      help to better address uncertain futures, thereby leading to more sustainable
      approaches.

PMID- 23535453
TI  - Comparison of spatial and temporal independent component analyses of
      electroencephalographic data: a simulation study.
AB  - OBJECTIVE: Some discrepancies between EEG and fMRI results may arise due to
      different data analysis strategies. Here a bunch of analytical approaches derived
      from fMRI domain are applied to simulated EEG data and results are compared with
      results of traditional EEG analysis. METHODS: Simulations were performed using
      SPM8 capabilities. Traditional EEG approach was implemented using EEGlab toolbox;
      fMRI approach was applied to sLORETA-transformed EEG data using GIFT toolbox. It
      was tested how well the two approaches are able to distinguish two simulated EEG
      sources that vary in their localization, frequency, and within- and between
      subject variation. RESULTS: With two widely spaced sources oscillating at
      different frequencies, both approaches were similarly effective. With two closely
      spaced sources oscillating at different frequencies, the EEGlab method performed
      somewhat better. However, it failed to distinguish two widely spaced sources if
      they oscillated at the same frequency and had the same temporal dynamics.
      CONCLUSION: The proposed approach is feasible to apply to EEG data, particularly
      in a study of temporally correlated processes occurring within the same frequency
      band. SIGNIFICANCE: The proposed approach is straightforward for comparison of
      EEG results with the existing fMRI framework and for investigation of neural
      networks in normal and pathological populations.

PMID- 23535454
TI  - In vivo human hippocampal cingulate connectivity: a corticocortical evoked
      potentials (CCEPs) study.
AB  - OBJECTIVE: To investigate the human limbic system using cortico-cortical evoked
      potential (CCEP), which reveals the brain networks. METHODS: Five patients with
      nonlesional medically intractable focal epilepsy with ictal onset outside the
      limbic system were enrolled. All patients underwent stereoelectroencephalogram
      electrode implantation in order to delineate the epileptogenic zone. Alternating
      1Hz electrical stimuli were delivered to the hippocampus and posterior cingulate
      gyrus. A total of sixty stimuli were averaged in each trial to obtain CCEP
      responses. RESULTS: Hippocampal stimulation elicited prominent CCEP responses in
      the posterior cingulate gyrus. The latencies of early (N1) and late (N2) negative
      peak ranged 20-60 ms and 102-175 ms respectively. In addition, CCEP responses
      were observed in the posterior parahippocampal gyrus, medial superior frontal
      gyrus (SFG) and orbitofrontal cortex. Stimulation of posterior cingulate contacts
      induced CCEPs in the hippocampus with N1 and N2 latencies of 25-43 ms and 90-234
      ms respectively in all five patients. CONCLUSION: This finding supports the
      assertion that the hippocampus is connected with the posterior cingulate gyrus,
      posterior parahippocampal gyrus, medial SFG and orbitofrontal cortex. The
      hippocampus and posterior cingulate gyrus have a bidirectional network through
      the cingulum. SIGNIFICANCE: The present study provides new insight into the human
      limbic network.

PMID- 23535455
TI  - Using a motor imagery questionnaire to estimate the performance of a Brain
      Computer Interface based on object oriented motor imagery.
AB  - OBJECTIVES: The primary objective was to test whether motor imagery (MI)
      questionnaires can be used to detect BCI 'illiterate'. The second objective was
      to test how different MI paradigms, with and without the physical presence of the
      goal of an action, influence a BCI classifier. METHODS: Kinaesthetic (KI) and
      visual (VI) motor imagery questionnaires were administered to 30 healthy
      volunteers. Their EEG was recorded during a cue-based, simple imagery (SI) and
      goal oriented imagery (GOI). RESULTS: The strongest correlation (Pearson
      r(2)=0.53, p=1.6e-5) was found between KI and SI, followed by a moderate
      correlation between KI and GOI (r(2)=0.33, p=0.001) and a weak correlation
      between VI and SI (r(2)=0.21, p=0.022) and VI and GOI (r(2)=0.17, p=0.05).
      Classification accuracy was similar for SI (71.1 +/- 7.8%) and GOI (70.5 +/-
      5.9%) though corresponding classification features differed in 70% participants.
      Compared to SI, GOI improved the classification accuracy in 'poor' imagers while
      reducing the classification accuracy in 'very good' imagers. CONCLUSION: The KI
      score could potentially be a useful tool to predict the performance of a MI based
      BCI. The physical presence of the object of an action facilitates motor
      imagination in 'poor' able-bodied imagers. SIGNIFICANCE: Although this study
      shows results on able-bodied people, its general conclusions should be
      transferable to BCI based on MI for assisted rehabilitation of the upper
      extremities in patients.

PMID- 23535456
TI  - Bladder outlet obstruction triggers neural plasticity in sensory pathways and
      contributes to impaired sensitivity in erectile dysfunction.
AB  - Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common
      problems in aging males worldwide. The objective of this work was to evaluate the
      effects of bladder neck nerve damage induced by partial bladder outlet
      obstruction (PBOO) on sensory innervation of the corpus cavernosum (CC) and CC
      smooth muscle (CCSM) using a rat model of PBOO induced by a partial ligation of
      the bladder neck. Retrograde labeling technique was used to label dorsal root
      ganglion (DRG) neurons that innervate the urinary bladder and CC. Contractility
      and relaxation of the CCSM was studied in vitro, and expression of nitric oxide
      synthase (NOS) was evaluated by Western blotting. Concentration of the sensory
      neuropeptides substance P (SP) and calcitonin gene-related peptide was measured
      by ELISA. Partial obstruction of the bladder neck caused a significant
      hypertrophy of the urinary bladders (2.5-fold increase at 2 wk). Analysis of L6
      S2 DRG sections determined that sensory ganglia received input from both the
      urinary bladder and CC with 5-7% of all neurons double labeled from both organs.
      The contractile responses of CC muscle strips to KCl and phenylephrine were
      decreased after PBOO, followed by a reduced relaxation response to nitroprusside.
      A significant decrease in neuronal NOS expression, but not in endothelial NOS or
      protein kinase G (PKG-1), was detected in the CCSM of the obstructed animals.
      Additionally, PBOO caused some impairment to sensory nerves as evidenced by a
      fivefold downregulation of SP in the CC (P <= 0.001). Our results provide
      evidence that PBOO leads to the impairment of bladder neck afferent innervation
      followed by a decrease in CCSM relaxation, downregulation of nNOS expression, and
      reduced content of sensory neuropeptides in the CC smooth muscle. These results
      suggest that nerve damage in PBOO may contribute to LUTS-ED comorbidity and
      trigger secondary changes in the contraction/relaxation mechanisms of CCSM.

PMID- 23535457
TI  - Exhausting exercise and tissue-specific expression of monocarboxylate
      transporters in rainbow trout.
AB  - Transmembrane lactate movements are mediated by monocarboxylate transporters
      (MCTs), but these proteins have never been characterized in rainbow trout. Our
      goals were to clone potential trout MCTs, determine tissue distribution, and
      quantify the effects of exhausting exercise on MCT expression. Such information
      could prove important to understand the mechanisms underlying the classic
      "lactate retention" seen in trout white muscle after intense exercise. Four
      isoforms were identified and partially characterized in rainbow trout: MCT1a,
      MCT1b, MCT2, and MCT4. MCT1b was the most abundant in heart and red muscle but
      poorly expressed in the gill and brain where MCT1a and MCT2 were prevalent. MCT
      expression was strongly stimulated by exhausting exercise in brain (MCT2: +260%)
      and heart (MCT1a: +90% and MCT1b: +50%), possibly to increase capacity for
      lactate uptake in these highly oxidative tissues. By contrast, the MCTs of gill,
      liver, and muscle remained unaffected by exercise. This study provides a possible
      functional explanation for postexercise "lactate retention" in trout white
      muscle. Rainbow trout may be unable to release large lactate loads rapidly during
      recovery because: 1) they only poorly express MCT4, the main lactate exporter
      found in mammalian glycolytic muscles; 2) the combined expression of all trout
      MCTs is much lower in white muscle than in any other tissue; and 3) exhausting
      exercise fails to upregulate white muscle MCT expression. In this tissue,
      carbohydrates act as an "energy spring" that alternates between explosive power
      release during intense swimming (glycogen to lactate) and recoil during
      protracted recovery (slow glycogen resynthesis from local lactate).

PMID- 23535458
TI  - Brain stem representation of thermal and psychogenic sweating in humans.
AB  - Functional MRI was used to identify regions in the human brain stem activated
      during thermal and psychogenic sweating. Two groups of healthy participants aged
      34.4 +/- 10.2 and 35.3 +/- 11.8 years (both groups comprising 1 woman and 10 men)
      were either heated by a water-perfused tube suit or subjected to a Stroop test,
      while they lay supine with their head in a 3-T MRI scanner. Sweating events were
      recorded as electrodermal responses (increases in AC conductance) from the palmar
      surfaces of fingers. Each experimental session consisted of two 7.9-min runs,
      during which a mean of 7.3 +/- 2.1 and 10.2 +/- 2.5 irregular sweating events
      occurred during psychogenic (Stroop test) and thermal sweating, respectively. The
      electrodermal waveform was used as the regressor in each subject and run to
      identify brain stem clusters with significantly correlated blood oxygen level
      dependent signals in the group mean data. Clusters of significant activation were
      found with both psychogenic and thermal sweating, but a voxelwise comparison
      revealed no brain stem cluster whose signal differed significantly between the
      two conditions. Bilaterally symmetric regions that were activated by both
      psychogenic and thermal sweating were identified in the rostral lateral midbrain
      and in the rostral lateral medulla. The latter site, between the facial nuclei
      and pyramidal tracts, corresponds to a neuron group found to drive sweating in
      animals. These studies have identified the brain stem regions that are activated
      with sweating in humans and indicate that common descending pathways may mediate
      both thermal and psychogenic sweating.

PMID- 23535461
TI  - Changes in fetal lamb arterial blood gas and acid-base status with advancing
      gestation.
AB  - To determine whether there are changes in blood gas and acid-base status with
      advancing gestation in the fetal lamb, similar to that reported in the human
      fetus, blood gas, acid-base, and blood metabolite values were measured in 447
      control, arterial blood samples from 108 chronically instrumented fetal lambs
      between 103 and 146 days gestation. With advancing gestation, Po(2), pH, O(2)
      saturation, and O(2) content fell significantly, while Pco(2) and hemoglobin
      concentration increased. Blood glucose and lactate concentrations were unchanged,
      although the lactate level increased with decreasing Po(2), particularly when
      below ~13 mmHg. Multiple linear regression indicated that increasing fetal number
      was associated with decreased Po(2) and glucose level and increased pH, HCO(3)(
      ), base excess, and lactate concentration. Hemoglobin concentration was higher in
      female than male lambs. Overall, there was a linear relationship between glucose
      concentration and birth weight. It is concluded that in fetal lambs as in the
      human fetus, there are changes in blood gas and acid-base status with advancing
      gestation. This may be due to the decrease in fetal weight-normalized uterine and
      umbilical blood flows than occurs in these and other species as gestation
      proceeds. In addition, the reduced birth weight in twin and triplet lambs may be
      due to hypoglycemia rather than hypoxemia.

PMID- 23535459
TI  - Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius.
AB  - The present study sought to determine whether the protein catabolic response in
      skeletal muscle produced by chronic alcohol feeding was exaggerated in aged rats.
      Adult (3 mo) and aged (18 mo) female F344 rats were fed a nutritionally complete
      liquid diet containing alcohol (36% of total calories) or an isocaloric
      isonitrogenous control diet for 20 wk. Muscle (gastrocnemius) protein synthesis,
      as well as mTOR and proteasome activity did not differ between control-fed adult
      and aged rats, despite the increased TNF-alpha and IL-6 mRNA and decreased IGF-I
      mRNA in muscle of aged rats. Compared with alcohol-fed adult rats, aged rats
      demonstrated an exaggerated alcohol-induced reduction in lean body mass and
      protein synthesis (both sarcoplasmic and myofibrillar) in gastrocnemius. Alcohol
      fed aged rats had enhanced dephosphorylation of 4E-BP1, as well as enhanced
      binding of raptor with both mTOR and Deptor, and a decreased binding of raptor
      with 4E-BP1. Alcohol feeding of both adult and aged rats reduced RagA binding to
      raptor. The LKB1-AMPK-REDD1 pathway was upregulated in gastrocnemius from alcohol
      fed aged rats. These exaggerated alcohol-induced effects in aged rats were
      associated with a greater decrease in muscle but not circulating IGF-I, but no
      further increase in inflammatory mediators. In contrast, alcohol did not
      exaggerate the age-induced increase in atrogin-1 and MuRF1 mRNA or the increased
      proteasome activity. Our results demonstrate that, compared with adult rats, the
      gastrocnemius from aged rats is more sensitive to the catabolic effects of
      alcohol on protein synthesis, but not protein degradation, and this exaggerated
      response may be AMPK-dependent.

PMID- 23535462
TI  - Deletion of cyclooxygenase-2 in the mouse increases arterial blood pressure with
      no impairment in renal NO production in response to chronic high salt intake.
AB  - Experiments were designed to test the hypothesis that cyclooxygenase-2 (COX-2)
      activity attenuates the blood pressure increase during high NaCl intake by
      stimulation of endothelial nitric oxide synthase (eNOS)-mediated NO synthesis in
      the kidney medulla. COX-2(-/-) (C57BL6) an COX-2(+/+) mice were fed a diet with
      0.004% (low salt, LS) or 4% (high salt, HS) NaCl for 18 days. Arterial blood
      pressure was recorded continuously using indwelling catheters. Food and water
      intake and diuresis were measured in metabolic cages. Urine osmolality and
      excretion of electrolytes, cGMP, cAMP, and NOx were determined, as well as plasma
      NOx and cGMP. There was a significant dependence of blood pressure on salt intake
      and genotype: COX-2(-/-) exhibited higher blood pressure than COX-2(+/+) both on
      HS and LS intake. COX-2(+/+) littermates displayed an increase in blood pressure
      on HS versus LS (102.3 +/- 1.1 mmHg vs. 91.9 +/- 0.9 mmHg) day and night. The
      mice exhibited significant blood pressure increases during the awake phase
      (night) that were larger in COX-2(-/-) on HS diet compared with COX-2(+/+). Water
      intake, diuresis, Na(+), and osmolyte excretions and NOx and cGMP excretions were
      significantly and similarly elevated with HS in COX-2(-/-) and COX-2(+/+). In
      summary, C57BL6 mice exhibit a salt intake-dependent increase in arterial blood
      pressure with increased renal NO production. COX-2 activity has a general
      lowering effect on arterial blood pressure. COX-2 dampens NaCl-induced increases
      in arterial blood pressure in the awake phase. In conclusion, COX-2 activity
      attenuates the changes in nocturnal blood pressure during high salt intake, and
      COX-2 activity is not necessary for increased renal nitric oxide formation during
      elevated NaCl intake.

PMID- 23535463
TI  - Study of genetic variants in common cancers paves way for targeted screening.

PMID- 23535460
TI  - Hypertension in mice with transgenic activation of the brain renin-angiotensin
      system is vasopressin dependent.
AB  - An indispensable role for the brain renin-angiotensin system (RAS) has been
      documented in most experimental animal models of hypertension. To identify the
      specific efferent pathway activated by the brain RAS that mediates hypertension,
      we examined the hypothesis that elevated arginine vasopressin (AVP) release is
      necessary for hypertension in a double-transgenic model of brain-specific RAS
      hyperactivity (the "sRA" mouse model). sRA mice experience elevated brain RAS
      activity due to human angiotensinogen expression plus neuron-specific human renin
      expression. Total daily loss of the 4-kDa AVP prosegment (copeptin) into urine
      was grossly elevated (>=8-fold). Immunohistochemical staining for AVP was
      increased in the supraoptic nucleus of sRA mice (~2-fold), but no quantitative
      difference in the paraventricular nucleus was observed. Chronic subcutaneous
      infusion of a nonselective AVP receptor antagonist conivaptan (YM-087, Vaprisol,
      22 ng/h) or the V(2)-selective antagonist tolvaptan (OPC-41061, 22 ng/h) resulted
      in normalization of the baseline (~15 mmHg) hypertension in sRA mice. Abdominal
      aortas and second-order mesenteric arteries displayed AVP-specific
      desensitization, with minor or no changes in responses to phenylephrine and
      endothelin-1. Mesenteric arteries exhibited substantial reductions in V(1A)
      receptor mRNA, but no significant changes in V(2) receptor expression in kidney
      were observed. Chronic tolvaptan infusion also normalized the (5 mmol/l)
      hyponatremia of sRA mice. Together, these data support a major role for
      vasopressin in the hypertension of mice with brain-specific hyperactivity of the
      RAS and suggest a primary role of V(2) receptors.

PMID- 23535464
TI  - Cushing's syndrome.

PMID- 23535465
TI  - Structural changes in amorphous Ge(x)SiO(y) on the way to nanocrystal formation.
AB  - Temperature induced changes of the local chemical structure of bulk amorphous
      GexSiOy are studied by Ge K-edge x-ray absorption near-edge spectroscopy and Si
      L2/3-edge x-ray Raman scattering spectroscopy. Different processes are revealed
      which lead to formation of Ge regions embedded in a Si oxide matrix due to
      different initial structures of as-prepared samples, depending on their Ge/Si/O
      ratio and temperature treatment, eventually resulting in the occurrence of
      nanocrystals. Here, disproportionation of GeOx and SiOx regions and/or reduction
      of Ge oxides by pure Si or by a surrounding Si sub-oxide matrix can be employed
      to tune the size of Ge nanocrystals along with the chemical composition of the
      embedding matrix. This is important for the optimization of the electronic and
      luminescent properties of the material.

PMID- 23535466
TI  - Conceptual framework and mathematical model for the transport of metal-chelant
      complexes during in situ soil remediation.
AB  - Understanding the transport of metal-chelant complexes is a challenging but
      necessary task for assessing the in situ chelant applications for land
      remediation and the potential environmental risks. This study presented an
      integrated conceptual framework for delineating primary and secondary
      interactions between target metals, chelants and soil components. The
      mathematical transport model based on primary interactions reasonably simulated
      the breakthrough curves of multiple target metals (Cu, Zn, Pb, Cr, and Ni) and
      mineral cations (Fe, Al, Mg, Mn, and Ca) during EDTA flushing of a field
      contaminated soil. The first-order extraction rates of target metals were on the
      order of 10(-6)s(-1), except Zn (10(-4)s(-1)) due to exceptionally large
      extractable amount in the soil. These rates compared well with previously
      reported values for field-contaminated soil, but were much smaller than those for
      artificially contaminated soil. The first-order dissolution rates of mineral
      cations (10(-6)-10(-5)s(-1)) were similar to the reported values for crystalline
      minerals, except Ca (10(-4)s(-1)) because of substantial proton-induced
      dissolution of carbonates. Nevertheless, due to a wide spectrum of extraction and
      dissolution rates at different stages, the model provided a more conservative
      prediction (i.e., overestimation) of metal-chelant transport while underestimated
      the transport of free chelant. Further revision of the proposed model may improve
      its prediction accuracy but attention should be paid to the model complexity and
      the number of adjustable parameters.

PMID- 23535467
TI  - Systematic investigation of the toxicity interaction of ZnSe@ZnS QDs on BSA by
      spectroscopic and microcalorimetry techniques.
AB  - The interaction of ZnSe@ZnS quantum dots (QDs) and bovine serum albumin (BSA) was
      investigated by means of fluorescence (FL) spectrometry, circular dichroism (CD)
      spectra, and isothermal titration calorimetry (ITC). The fluorescence intensity
      of BSA decreased regularly with the increasing of QDs concentration. The decrease
      of BSA fluorescence intensity was proved to be a kind of static quenching. CD
      results show the helicity of BSA decreased from 38.04% to 26.51% with the
      addition of QDs, which suggests a stronger structural change that is related to a
      low degree of surface coverage. And also, both ion strength and pH value could
      affect the interaction between BSA and QDs, suggesting that both the static
      electronic attraction and H-bond contribute to the interaction between BSA and
      QDs. The thermodynamics of interaction between BSA and QDs were calculated from
      ITC data. Both enthalpy and entropy changes were favorable for the interaction in
      Tris-buffer, while only enthalpy change was favorable for the interaction in NaCl
      or HCl solution. 

PMID- 23535468
TI  - Nitrogen dioxide (NO(2)) pollution as a potential risk factor for developing
      vascular dementia and its synaptic mechanisms.
AB  - Recent epidemiological literatures reported that NO(2) is a potential risk factor
      of ischemic stroke in polluted area. Meanwhile, our previous in vivo study found
      that NO(2) could delay the recovery of nerve function after stroke, implying a
      possible risk of vascular dementia (VaD) with NO(2) inhalation, which is often a
      common cognitive complication resulting from stroke. However, the effect and
      detailed mechanisms have not been fully elucidated. In the present study,
      synaptic mechanisms, the foundation of neuronal function and viability, were
      investigated in both model rats of ischemic stroke and healthy rats after NO(2)
      exposure. Transmission electron microscope (TEM) observation showed that 5 mg m(
      3) NO(2) exposure not only exacerbated the ultrastructural impairment of synapses
      in stroke model rats, but also induced neuronal damage in healthy rats. Meantime,
      we found that the expression of synaptophysin (SYP) and postsynaptic density
      protein 95 (PSD-95), two structural markers of synapses in ischemic stroke model
      were inhibited by NO(2) inhalation; and so it was with the key proteins mediating
      long-term potentiation (LTP), the major form of synaptic plasticity. On the
      contrary, NO(2) inhalation induced the expression of nearly all these proteins in
      healthy rats in a concentration-dependent manner. Our results implied that NO(2)
      exposure could increase the risk of VaD through inducing excitotoxicity in
      healthy rats but weakening synaptic plasticity directly in stroke model rats.

PMID- 23535469
TI  - Pesticide contamination interception strategy and removal efficiency in forest
      buffer and artificial wetland in a tile-drained agricultural watershed.
AB  - Pesticide pollution is a major threat to aquatic ecosystems that can be mitigated
      through complementary actions including buffer zones (BZs). This paper discusses
      the results of 3 yr of field-scale monitoring of the concentration and load
      transfer of 16 pesticides out of a tile-drained catchment (Bray, France) and
      their reduction through two BZ: an artificial wetland (AW) and a forest buffer
      (FB). Typically, the highest concentrations were measured in the first flows
      following pesticide applications or resuming after periods of low or no flow. An
      open/close water management strategy was implemented to operate the parallel BZ
      based on pesticide applications by the farmer. The strategy was efficient in
      intercepting molecules whose highest concentrations occurred during the first
      flows following application. Inlet vs. outlet pesticide load reductions ranged
      from 45% to 96% (AW) and from -32% to 100% (FB) depending on the pesticide
      molecule and the hydrological year. Partly reversible adsorption was a dominant
      process explaining pesticide removal; whereas, degradation occurred for
      sufficiently long water retention time. Apart from the least sorbing molecules
      (e.g., isoproturon), BZ can partially remove pesticide pollution.

PMID- 23535470
TI  - Atmospheric deposition of trace elements recorded in snow from the Mt.
      Nyainqentanglha region, southern Tibetan Plateau.
AB  - In May 2009, snowpit samples were collected from a high-elevation glacier in the
      Mt. Nyainqentanglha region on the southern Tibetan Plateau. A set of elements
      (Al, V, Cr, Mn, Co, Ni, Cu, Zn, Cd, Hg and Pb) was analyzed to investigate the
      concentrations, deposition fluxes of trace elements, and the relative
      contributions from anthropogenic and natural sources deposited on the southern
      Tibetan Plateau. Concentrations of most of the trace elements in snowpit samples
      from the Zhadang glacier are significantly lower than those examined from central
      Asia (e.g., eastern Tien Shan), with higher concentrations during the non-monsoon
      season than during the monsoon season. The elements of Al, V, Cr, Mn, Co, and Ni
      display low crustal enrichment factors (EFs), while Cu, Zn, Cd, Hg, and Pb show
      high EF values in the snow samples, suggesting anthropogenic inputs are
      potentially important for these elements in the remote, high-elevation atmosphere
      on the southern Tibetan Plateau. Together with the fact that the concentration
      levels of such elements in the Mt. Nyainqentanglha region are significantly
      higher than those observed on the south edge of the Tibetan Plateau, our results
      suggest that the high-elevation atmosphere on the southern Tibetan Plateau may be
      more sensitive to variations in the anthropogenic emissions of atmospheric trace
      elements than that in the central Himalayas. Moreover, the major difference
      between deposition fluxes estimated in our snow samples and those recently
      measured at Nam Co Station for elements such as Cr and Cu may suggest that
      atmospheric deposition of some of trace elements reconstructed from snowpits and
      ice cores could be grossly underestimated on the Tibetan Plateau. 

PMID- 23535471
TI  - Global risk of pharmaceutical contamination from highly populated developing
      countries.
AB  - Global pharmaceutical industry has relocated from the west to Asian countries to
      ensure competitive advantage. This industrial relocation has posed serious
      threats to the environment. The present study was carried out to assess the
      possible pharmaceutical contamination in the environment of emerging
      pharmaceutical manufacturing countries (Bangladesh, China, India and Pakistan).
      Although these countries have made tremendous progress in the pharmaceutical
      sector but most of their industrial units discharge wastewater into domestic
      sewage network without any treatment. The application of untreated wastewater
      (industrial and domestic) and biosolids (sewage sludge and manure) in agriculture
      causes the contamination of surface water, soil, groundwater, and the entire food
      web with pharmaceutical compounds (PCs), their metabolites and transformed
      products (TPs), and multidrug resistant microbes. This pharmaceutical
      contamination in Asian countries poses global risks via product export and
      international traveling. Several prospective research hypotheses including the
      development of new analytical methods to monitor these PCs/TPs and their
      metabolites, highly resistant microbial strains, and mixture toxicity as a
      consequence of pharmaceutical contamination in these emerging pharmaceutical
      exporters have also been proposed based on the available literature. 

PMID- 23535472
TI  - [Rose is a rose is a rose].

PMID- 23535473
TI  - [Between anxiety and hope: the experiences of women with vulval intraepithelial
      neoplasia during their illness trajectory - a qualitative approach].
AB  - The vulvar intraepithelial neoplasia (VIN) is a rare chronic skin condition that
      may progress to an invasive carcinoma of the vulva. Major issues affecting
      women's health were occurring symptoms, negative influences on sexuality,
      uncertainty concerning the illness progression and changes in the body image.
      Despite this, there is little known about the lived experiences of the illness
      trajectory. Therefore, the aim of this study was to describe the experiences of
      women with VIN during the illness trajectory. In a secondary data analysis of the
      foregoing qualitative study we analysed eight narrative interviews with women
      with VIN by using thematic analysis in combination with critical hermeneutics.
      Central for these women during their course of illness was a sense of "Hope and
      Fear". This constitutive pattern reflects the fear of recurrence but also the
      trust in healing. The eight narratives showed women's experiences during their
      course of illness occurred in five phases: "there is something unknown"; "one
      knows, what IT is"; "IT is treated and should heal"; "IT has effects on daily
      life"; "meanwhile it works". Women's experiences were particularly influenced by
      the feeling of "embarrassment" and by "dealing with professionals". Current care
      seems to lack adequate support for women with VIN to manage these phases. We
      suggest, based on our study and the international literature, that new models of
      counselling and providing information need to be developed and evaluated.

PMID- 23535474
TI  - [Living with a multitude of medicaments: experiences of patients with cancer].
AB  - The ability to handle a complex medication regimen is important for patients with
      cancer being treated on an outpatient basis, because many of them have to take
      drugs for oral chemotherapy, against cancer-related symptoms, side effects of the
      treatments, and preexisting conditions. This qualitative study examined how
      patients experienced a complex medication regimen and how they managed it at
      home. Interviews were conducted with 12 patients from oncology outpatients units
      and analysed by means of content analysis. Patients knew their medications. They
      took them mainly as prescribed because they regarded them as a safeguard against
      deterioration and a life-saver. In addition, they trusted their doctors and felt
      obliged to them to take the medications. The doctor-patient relationship was
      supported by constant treatment settings. Even so, the patients would rather have
      taken less or no medications at all, primarily because of fear of side effects.
      In order to guarantee a regular intake, the patients linked the medications with
      specific places, times, and activities and developed routines and rituals. Nurses
      were hardly perceived with regard to medications and medication management. It is
      recommended that patients with complex medication regimens are assigned to
      constant mentors amongst health professionals. These mentors should check
      patients' medication knowledge, attitudes and management strategies on a regular
      basis and either encourage sound performance or assist patients in developing an
      acceptable way of medication taking and handling.

PMID- 23535476
TI  - [Comparing quality measurements Part 2: control charts].
AB  - Comparative quality measurements and evaluations in nursing play significant
      roles. Quality measures are affected by systematic and random error. Statistical
      Process Control (SPC) offers a method to take random variation adequately into
      account. In this article, control charts are introduced. Those are graphical
      displays to show quality measures over time. Attribute variables can be displayed
      by p-, u- and c-control charts. Special cause variations within the processes can
      be detected by rules. If signs for special cause variations are absent, the
      process in considered being in statistical control showing common cause
      variation. A deviation of one data point greater than three standard deviations
      from the arithmetic mean is considered the strongest signal for non random
      variation within the process. Within quality improvement contexts control charts
      outperform traditional comparisons of means and spreads.

PMID- 23535475
TI  - [Inflammatory bowel diseases: experiencing illness, therapy and care].
AB  - People affected by Crohn's disease or ulcerative colitis experience a high level
      of suffering. A new generation of anti-tumour necrosis factor-alpha agents can
      alleviate the burden of symptoms considerably. In order to develop a need-centred
      care programme for this patient group, we conducted problem-centred interviews
      with nine patients about their experience of the disease, the therapy and the
      quality of nursing care. The evaluation was based on qualitative content
      analysis. Patients' statements revealed three general categories: (1) "the never
      ending story" of a life with IBD, (2) "the sudden change" due to successful
      therapy and (3) "the narrow path" of a new stage of life: the disease no longer
      dominated daily life. The results emphasise the necessity of specific care for
      this patient group in order to perceptibly enhance their self-management and
      quality of life. The study illuminates a developing field of ambulant nursing
      care, based on the knowledge of patients' needs in the context of a chronic
      disease characterised by an unpredictable and irregular course.

PMID- 23535477
TI  - [Including family in nursing care of patients with delirium on intensive care
      units].

PMID- 23535478
TI  - [What is the value or harm of Cronbach's alpha?].

PMID- 23535479
TI  - ["Implications and effects of the Resident Assessment Instrument (RAI Home Care
      2.0) in ambulatory nursing care"].

PMID- 23535485
TI  - [In memory of Christoph Abderhalden].

PMID- 23535489
TI  - Timed 25-foot walk: direct evidence that improving 20% or greater is clinically
      meaningful in MS.
AB  - OBJECTIVE: In this study, we used data from clinical trials of dalfampridine
      (fampridine outside the United States) to re-examine the clinical meaningfulness
      of Timed 25-Foot Walk (T25FW) changes. METHODS: Pooled data were analyzed from 2
      phase III randomized placebo-controlled clinical trials of dalfampridine in
      multiple sclerosis (MS) (n = 533). Walking speed (T25FW) and patient-reported
      walking ability (MS Walking Scale-12 [MSWS-12]) were measured, concurrently,
      multiple times before and during treatment. We examined T25FW speed variability
      within and between visits, correlations of T25FW speed with MSWS-12 score, and
      changes in MSWS-12 (mean scores, effect sizes) associated with percent T25FW
      changes. RESULTS: T25FW speed variability was small (within- and between-visit
      averages = 7.2%-8.7% and 14.4%-16.3%). Correlations between T25FW and MSWS-12
      values were low (-0.20 to -0.30), but relatively stronger between their change
      values (-0.33 to -0.41). Speed improvements of >20%, and possibly 15%, were
      associated with clinically meaningful changes in self-reported walking ability
      using MSWS-12 change score and effect size criteria. CONCLUSIONS: This study
      builds on existing research and provides direct evidence that improvements in
      T25FW speed of >= 20% are meaningful to people with MS. The dalfampridine data
      enabled examinations previously not possible, including spontaneous and induced
      speed changes, speed change anchored to change in self-reported walking ability,
      and a profile of speed changes. Results support the T25FW as a clinically
      meaningful outcome measure for MS clinical trials.

PMID- 23535488
TI  - Comparing the effects of food restriction and overeating on brain reward systems.
AB  - Both caloric restriction and overeating have been shown to affect neural
      processes associated with reinforcement. Both preclinical and some clinical
      studies have provided evidence that food restriction may increase reward
      sensitivity, and while there are mixed findings regarding the effects of
      overeating on reward sensitivity, there is strong evidence linking this behavior
      with changes in reward-related brain regions. Evidence of these changes comes in
      part from findings that show that such eating patterns are associated with
      increased drug use. The data discussed here regarding the differential effects of
      various eating patterns on reward systems may be particularly relevant to the
      aging population, as this population has been shown to exhibit altered reward
      sensitivity and decreased caloric consumption. Moreover, members of this
      population appear to be increasingly affected by the current obesity epidemic.
      Food, like alcohol or drugs, can stimulate its own consumption and produce
      similar neurochemical changes in the brain. Age-related loss of appetite,
      decreased eating, and caloric restriction are hypothesized to be associated with
      changes in the prevalence of substance misuse, abuse, and dependence seen in this
      cohort. 

PMID- 23535490
TI  - PRRT2 mutation correlated with phenotype of paroxysmal kinesigenic dyskinesia and
      drug response.

PMID- 23535491
TI  - The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for
      Parkinson disease.
AB  - OBJECTIVE: To study the possible association of founder mutations in the
      lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs,
      Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson
      disease (PD). METHODS: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry,
      that included a total of 938 patients, were studied: a cohort of 654 patients
      from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ
      founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The
      frequencies of these mutations were compared to AJ control groups that included
      large published groups undergoing prenatal screening and 282 individuals matched
      for age and sex. RESULTS: Mutation frequencies were similar in the 2 groups of
      patients with PD. The SMPD1 p.L302P was strongly associated with a highly
      increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9-22.8, p <
      0.0001), as 9/938 patients with PD were carriers of this mutation compared to
      only 11/10,709 controls. CONCLUSIONS: The SMPD1 p.L302P mutation is a novel risk
      factor for PD. Although it is rare on a population level, the identification of
      this mutation as a strong risk factor for PD may further elucidate PD
      pathogenesis and the role of lysosomal pathways in disease development.

PMID- 23535492
TI  - ADORA2A polymorphism predisposes children to encephalopathy with febrile status
      epilepticus.
AB  - OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion
      (AESD) is a childhood encephalopathy following severe febrile seizures, leaving
      neurologic sequelae in many patients. However, its pathogenesis remains unclear.
      In this study, we clarified that genetic variation in the adenosine A2A receptor
      (ADORA2A), whose activation is involved in excitotoxicity, may be a predisposing
      factor of AESD. METHODS: We analyzed 4 ADORA2A single nucleotide polymorphisms in
      85 patients with AESD. The mRNA expression in brain samples, mRNA and protein
      expression in lymphoblasts, as well as the production of cyclic adenosine
      monophosphate (cAMP) by lymphoblasts in response to adenosine were compared among
      ADORA2A diplotypes. RESULTS: Four single nucleotide polymorphisms were completely
      linked, which resulted in 2 haplotypes, A and B. Haplotype A (C at rs2298383, T
      at rs5751876, deletion at rs35320474, and C at rs4822492) frequency in patients
      was significantly higher than in controls (p = 0.005). Homozygous haplotype A (AA
      diplotype) had a higher risk of developing AESD (odds ratio 2.32, 95% confidence
      interval 1.32-4.08; p = 0.003) via a recessive model. mRNA expression was
      significantly higher in AA than AB and BB diplotypes, both in the brain (p =
      0.003 and 0.002, respectively) and lymphoblasts (p = 0.035 and 0.003,
      respectively). In lymphoblasts, ADORA2A protein expression (p = 0.024), as well
      as cellular cAMP production (p = 0.0006), was significantly higher in AA than BB
      diplotype. CONCLUSIONS: AA diplotype of ADORA2A is associated with AESD and may
      alter the intracellular adenosine/cAMP cascade, thereby promoting seizures and
      excitotoxic brain damage in patients.

PMID- 23535493
TI  - Incidence of atrial fibrillation detected by implantable loop recorders in
      unexplained stroke.
AB  - OBJECTIVES: The usefulness of the implantable loop recorder (ILR) with improved
      atrial fibrillation (AF) detection capability (Reveal XT) and the factors
      associated with AF in the setting of unexplained stroke were investigated.
      METHODS: A cohort study is reported of 51 patients in whom ILRs were implanted
      for the investigation of ischemic stroke for which no cause had been found
      (cryptogenic) following appropriate vascular and cardiac imaging and at least 24
      hours of cardiac rhythm monitoring. RESULTS: The patients were aged from 17 to 73
      (median 52) years. Of the 30 patients with a shunt investigation, 22 had a patent
      foramen ovale (73.3%; 95% confidence interval [CI] 56.5%-90.1%). AF was
      identified in 13 (25.5%; 95% CI 13.1%-37.9%) cases. AF was associated with
      increasing age (p = 0.018), interatrial conduction block (p = 0.02), left atrial
      volume (p = 0.025), and the occurrence of atrial premature contractions on
      preceding external monitoring (p = 0.004). The median (range) of monitoring prior
      to AF detection was 48 (0-154) days. CONCLUSION: In patients with unexplained
      stroke, AF was detected by ILR in 25.5%. Predictors of AF were identified, which
      may help to target investigations. ILRs may have a central role in the future in
      the investigation of patients with unexplained stroke.

PMID- 23535494
TI  - The search for paroxysmal atrial fibrillation in cryptogenic stroke: leave no
      stone unturned.
AB  - Atrial fibrillation (AF), a well-established cause of ischemic stroke, is found
      in up to 25% of first strokes.(1,2) Most patients with stroke from AF will
      benefit from anticoagulation for secondary stroke prevention, so finding AF as a
      cause of ischemic stroke is critical. Many patients with AF have paroxysmal AF
      (PAF), in which periods of normal sinus rhythm alternate with sometimes brief
      episodes of AF. Conventional monitoring for AF in the hospital or for a small
      number of days as an outpatient may therefore miss the diagnosis of PAF. Although
      most of the data to support anticoagulation for stroke patients with AF come from
      patients with continuous AF, PAF has a similar risk of stroke when compared to
      continuous AF(3,4) and there appears to be a similar benefit of anticoagulation
      in reducing the risk of stroke in patients with PAF.(3.)

PMID- 23535496
TI  - Lysosomal enzyme defects and Parkinson disease.

PMID- 23535495
TI  - Higher serum glucose levels are associated with cerebral hypometabolism in
      Alzheimer regions.
AB  - OBJECTIVE: To investigate whether higher fasting serum glucose levels in
      cognitively normal, nondiabetic adults were associated with lower regional
      cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially
      affected by Alzheimer disease (AD). METHODS: This is a cross-sectional study of
      124 cognitively normal persons aged 64 +/- 6 years with a first-degree family
      history of AD, including 61 APOEepsilon4 noncarriers and 63 carriers. An
      automated brain mapping algorithm characterized and compared correlations between
      higher fasting serum glucose levels and lower [(18)F]-fluorodeoxyglucose-PET
      rCMRgl measurements. RESULTS: As predicted, higher fasting serum glucose levels
      were significantly correlated with lower rCMRgl and were confined to the vicinity
      of brain regions preferentially affected by AD. A similar pattern of regional
      correlations occurred in the APOEepsilon4 noncarriers and carriers. CONCLUSIONS:
      Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may
      be associated with AD pathophysiology. Findings suggest that the risk imparted by
      higher serum glucose levels may be independent of APOEepsilon4 status. This study
      raises additional questions about the role of the metabolic process in the
      predisposition to AD and supports the possibility of targeting these processes in
      presymptomatic AD trials.

PMID- 23535497
TI  - Electroconvulsive therapy for severe neuropsychiatric lupus with psychosis.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder that
      requires long-term management and can have a profound impact on the quality of
      life of patients. Among patients with SLE, neuropsychiatric manifestations are
      fairly common, occurring in up to 75% of patients with SLE. Neuropsychiatric
      symptoms of SLE (NPSLE) presenting with psychosis, however, is less common, with
      a prevalence of up to 11%. Treatment of psychosis in NPSLE has largely involved
      antipsychotics and immunosuppressants, with not much in the literature about the
      use of electroconvulsive therapy (ECT) as a method of treatment. METHODS: We
      report 3 cases of patients who presented with psychosis during a lupus relapse,
      who were treated successfully with ECT after their symptoms did not improve on
      medical treatment. RESULTS AND CONCLUSION: Although all 3 patients were treated
      with antipsychotics and immunosuppressants simultaneously with the ECT sessions,
      the time scale of these 3 case studies suggests that ECT played a role in the
      resolution of these patients' symptoms. Our 3 cases highlight that ECT can be
      safely and effectively used in patients with NPSLE with prominent psychotic
      symptoms.

PMID- 23535498
TI  - Abdominal obesity and chronic stress interact to predict blunted cardiovascular
      reactivity.
AB  - Abdominal obesity and chronic stress have independent effects on cardiac
      autonomic regulation, and may also interact to influence cardiovascular
      reactivity. In addition to main effects, we hypothesized that abdominal obesity
      and chronic stress would interact and predict blunted cardiovascular reactivity.
      One hundred and twenty-two undergraduate students engaged in two stressful
      laboratory tasks while cardiovascular activity was assessed. Results indicated
      that higher abdominal obesity significantly predicted blunted systolic blood
      pressure (SBP) and mean arterial pressure (MAP) change, while chronic stress was
      not directly associated with any measure of cardiovascular reactivity.
      Furthermore, there was a significant interaction between abdominal obesity and
      chronic stress on SBP and MAP change such that among participants with higher
      chronic stress, higher abdominal obesity was significantly associated with
      reduced SBP and MAP reactivity. In addition, body-mass index (BMI), a measure of
      overall obesity, also had both main and interaction effects with chronic stress
      to predict blunted cardiovascular reactivity. These results suggest that
      abdominally obese individuals may incur difficulty in mounting appropriately
      sized cardiovascular responses during acute stress, particularly when under high
      levels of chronic stress. 

PMID- 23535499
TI  - EEG-neurofeedback and psychodynamic psychotherapy in a case of adolescent
      anhedonia with substance misuse: mood/theta relations.
AB  - There is substantial evidence confirming the efficacy of neurofeedback with
      applications in clinical, educational and optimal performance domains. However, a
      psychodynamically informed NF-approach needs exploration. A male (19 y), college
      student whose first year was being seriously compromised after severe, 18-month,
      polydrug misuse, was treated with 11 sessions including a 2-month follow-up of
      neurofeedback combined with short-term psychodynamic psychotherapy. Pre/post
      treatment and follow-up assessment with the Brief Psychiatric Rating Scale (BPRS)
      and the Montgomery-Asberg Depression Rating Scale confirmed that levels of
      psychopathology dropped almost to zero. Correlational evidence disclosed that
      SMR/theta training was positively associated with reduction in psychopathological
      ratings, largely due to theta amplitude reduction; the strongest relation being
      with reduced BPRS activation. Alpha/theta training was not correlated with
      clinical improvement. The combined treatment was found to be highly effective
      with the student who learned to deal with feelings of anhedonia and alienation.
      There was no relapse during the follow-up phase. Further research is recommended.

PMID- 23535500
TI  - Physical and mental health of transgender older adults: an at-risk and
      underserved population.
AB  - PURPOSE: This study is one of the first to examine the physical and mental health
      of transgender older adults and to identify modifiable factors that account for
      health risks in this underserved population. DESIGN AND METHODS: Utilizing data
      from a cross-sectional survey of lesbian, gay, bisexual, and transgender older
      adults aged 50 and older (N = 2,560), we assessed direct and indirect effects of
      gender identity on 4 health outcomes (physical health, disability, depressive
      symptomatology, and perceived stress) based on a resilience conceptual framework.
      RESULTS: Transgender older adults were at significantly higher risk of poor
      physical health, disability, depressive symptomatology, and perceived stress
      compared with nontransgender participants. We found significant indirect effects
      of gender identity on the health outcomes via fear of accessing health services,
      lack of physical activity, internalized stigma, victimization, and lack of social
      support; other mediators included obesity for physical health and disability,
      identity concealment for perceived stress, and community belonging for depressive
      symptomatology and perceived stress. Further analyses revealed that risk factors
      (victimization and stigma) explained the highest proportion of the total effect
      of gender identity on health outcomes. IMPLICATIONS: The study identifies
      important modifiable factors (stigma, victimization, health-related behaviors,
      and social support) associated with health among transgender older adults.
      Reducing stigma and victimization and including gender identity in
      nondiscrimination and hate crime statutes are important steps to reduce health
      risks. Attention to bolstering individual and community-level social support must
      be considered when developing tailored interventions to address transgender older
      adults' distinct health and aging needs.

PMID- 23535501
TI  - Regional lung derecruitment and inflammation during 16 hours of mechanical
      ventilation in supine healthy sheep.
AB  - BACKGROUND: Lung derecruitment is common during general anesthesia. Mechanical
      ventilation with physiological tidal volumes could magnify derecruitment, and
      produce lung dysfunction and inflammation. The authors used positron emission
      tomography to study the process of derecruitment in normal lungs ventilated for
      16 h and the corresponding changes in regional lung perfusion and inflammation.
      METHODS: Six anesthetized supine sheep were ventilated with VT=8 ml/kg and
      positive end-expiratory pressure=0. Transmission scans were performed at 2-h
      intervals to assess regional aeration. Emission scans were acquired at baseline
      and after 16 h for the following tracers: (1) F-fluorodeoxyglucose to evaluate
      lung inflammation and (2) NN to calculate regional perfusion and shunt fraction.
      RESULTS: Gas fraction decreased from baseline to 16 h in dorsal (0.31+/-0.13 to
      0.14+/-0.12, P<0.01), but not in ventral regions (0.61+/-0.03 to 0.63+/-0.07,
      P=nonsignificant), with time constants of 1.5-44.6 h. Although the vertical
      distribution of relative perfusion did not change from baseline to 16 h, shunt
      increased in dorsal regions (0.34+/-0.23 to 0.63+/-0.35, P<0.01). The average
      pulmonary net F-fluorodeoxyglucose uptake rate in six regions of interest along
      the ventral-dorsal direction increased from 3.4+/-1.4 at baseline to 4.1+/-1.5
      10(-3)/min after 16 h (P<0.01), and the corresponding average regions of interest
      F-fluorodeoxyglucose phosphorylation rate increased from 2.0+/-0.2 to 2.5+/-0.2
      10(-2)/min (P<0.01). CONCLUSIONS: When normal lungs are mechanically ventilated
      without positive end-expiratory pressure, loss of aeration occurs continuously
      for several hours and is preferentially localized to dorsal regions. Progressive
      lung derecruitment was associated with increased regional shunt, implying an
      insufficient hypoxic pulmonary vasoconstriction. The increased pulmonary net
      uptake and phosphorylation rates of F-fluorodeoxyglucose suggest an incipient
      inflammation in these initially normal lungs.

PMID- 23535502
TI  - Low-frequency neuromuscular depression is a consequence of a reduction in nerve
      terminal Ca2+ currents at mammalian motor nerve endings.
AB  - BACKGROUND: The decline in voluntary muscle contraction during low-frequency
      nerve stimulation is used clinically to assess the type and degree of
      neuromuscular block. The mechanism underlying this depression is unknown.
      METHODS: Simultaneous electrophysiological measurements of neurotransmitter
      release and prejunctional Ca currents were made at mouse neuromuscular junctions
      to evaluate the hypothesis that decreases in nerve terminal Ca currents are
      responsible for low-frequency depression. RESULTS: Under conditions generally
      used to measure Ca currents at the neuromuscular junction, increasing the
      frequency of nerve stimulation briefly from 0.017 to 0.1-1 Hz caused a
      simultaneous reduction in the release of the neurotransmitter acetylcholine to
      52.2 +/- 4.4% of control and the Ca current peak to 75.4 +/- 2.0% of control (P <
      0.001, n = 5 experiments for both measurements, mean +/- SEM for all data). In
      conditions used for train-of-four monitoring (4 stimuli, 2 Hz), neurotransmitter
      release declined to 42.0 +/- 1.0% of control and the Ca current peak declined to
      75.8 +/- 3.3% of control between the first and fourth stimulus (P < 0.001, n = 7
      experiments for both measurements). Depression in acetylcholine release during
      train-of-four protocols also occurred in the absence of neuromuscular-blocking
      drugs. DISCUSSION: The results demonstrate that neuromuscular depression during
      train-of-four monitoring is due to a decline in nerve terminal Ca currents, hence
      reducing the release of acetylcholine. As similar processes may come into play at
      higher stimulation frequencies, agents that antagonize the decline in Ca currents
      could be used to treat conditions in which neuromuscular depression can be
      debilitating.

PMID- 23535503
TI  - Use of high-definition computed tomography to assess endotracheal tube luminal
      narrowing after mechanical ventilation.

PMID- 23535504
TI  - Protect the lungs during abdominal surgery: it may change the postoperative
      outcome.

PMID- 23535505
TI  - Current approach to fertility preservation by embryo cryopreservation.
AB  - The ovaries are susceptible to damage following treatment with gonadotoxic
      chemotherapy, pelvic radiotherapy, and/or ovarian surgery. Gonadotoxic treatments
      have also been used in patients with various nonmalignant systemic diseases. Any
      women of reproductive age with a sufficiently high risk of developing future
      ovarian failure due to those medical interventions may benefit from embryo
      cryopreservation though the tools of assessment of such a risk are still not very
      precise. Furthermore, the risk assessment can be influenced by many other factors
      such as the delay expected after chemotherapy and the number of children desired
      in the future. Embryo cryopreservation is an established and most successful
      method of fertility preservation when there is sufficient time available to
      perform ovarian stimulation. This publication will review the current state,
      approach, and indications of embryo cryopreservation for fertility preservation.

PMID- 23535506
TI  - The genetic spectrum of familial hypercholesterolemia in Pakistan.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease
      caused by mutations in the genes coding for the low density lipoprotein receptor
      (LDLR), proprotein convertase subtilisin/kexin type-9 (PCSK9) or apo-lipoprotein
      B-100 (APOB). The aim of the present work was to determine the genetic basis of
      dyslipidemia in 11 unrelated Pakistani families. METHODS: High resolution melting
      (HRM), sequencing and restriction fragment length polymorphism (RFLP). RESULTS:
      Probands were screened for the promoter and all coding regions, including
      intron/exon boundaries, of LDLR and PCSK9 and part of exon 26 of APOB including
      p.(R3527Q). Two families were identified with previously unreported LDLR
      mutations (c.1019_1020delinsTG, p.(C340L) and c.1634G>A, p.(G545E)). Both
      probands had tendon xanthomas or xanthelasma and/or a history of cardiovascular
      disease. Co-segregation with hypercholesterolemia was demonstrated in both
      families. In silico studies predicted these variations to be damaging. In two
      families, novel PCSK9 variations were identified (exon2; c.314G>A, p.(R105Q) and
      exon3; c.464C>T, p.(P155L)). In silico studies suggested both were likely to be
      damaging, and family members carrying the p.(105Q) allele had lower total
      cholesterol levels, suggesting this is a loss-of-function mutation. For c.464C>T
      p.(P155L) the small number of relatives available precluded any strong inference.
      CONCLUSION: This report brings to seven the number of different LDLR mutations
      reported in FH patients from Pakistan and, as expected in this heterogeneous
      population, no common LDLR mutation has been identified.

PMID- 23535507
TI  - Novel genes detected by transcriptional profiling from whole-blood cells in
      patients with early onset of acute coronary syndrome.
AB  - BACKGROUND: Genome-wide expression analysis using microarrays has been used as a
      research strategy to discovery new biomarkers and candidate genes for a number of
      diseases. We aim to find new biomarkers for the prediction of acute coronary
      syndrome (ACS) with a differentially expressed mRNA profiling approach using
      whole genomic expression analysis in a peripheral blood cell model from patients
      with early ACS. METHODS AND RESULTS: This study was carried out in two phases. On
      phase 1 a restricted clinical criteria (ACS-Ph1, n=9 and CG-Ph1, n=6) was used in
      order to select potential mRNA biomarkers candidates. A subsequent phase 2 study
      was performed using selected phase 1 markers analyzed by RT-qPCR using a larger
      and independent casuistic (ACS-Ph2, n=74 and CG-Ph2, n=41). A total of 549 genes
      were found to be differentially expressed in the first 48 h after the ACS-Ph1.
      Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1,
      BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are
      differentially expressed in both phases of this study. CONCLUSIONS:
      Transcriptomic analysis by microarray technology demonstrated differential
      expression during a 48 h time course suggesting a potential use of some of these
      genes as biomarkers for very early stages of ACS, as well as for monitoring early
      cardiac ischemic recovery.

PMID- 23535508
TI  - Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are
      increased during initial neuromyelitis optica attacks.
AB  - BACKGROUND: The current 2006 neuromyelitis optica (NMO) criteria is useful for
      diagnosing NMO, however this criteria seemed to be insufficient at early stage of
      NMO. Hence, the development of diagnostic marker besides anti-aquaporin 4
      antibody at early stage of NMO may be required. Our main aim of this study is to
      test the usefulness of measuring cerebrospinal fluid (CSF) interleukin (IL)-6 and
      glial fibrillary acidic protein (GFAP) concentrations as early diagnostic markers
      during initial NMO attacks. METHODS: We investigated CSF IL-6 and GFAP
      concentrations in 13 NMO spectrum disorder (NMOSD) patients at initial attacks,
      24 idiopathic central nervous system inflammatory disease patients (9 optic
      neuritis, 9 myelitis and 6 encephalitis) and 20 other non-inflammatory
      neurological disorders (ONNDs) patients, retrospectively. RESULTS: The mean CSF
      IL-6 and GFAP concentrations during the initial NMOSD attack were 91.4 pg/ml and
      369.3 ng/ml, respectively, and were significantly higher than in ONNDs,
      idiopathic optic neuritis and myelitis patients (P<0.01). The sensitivity of high
      CSF IL-6 during initial NMO attack was 76.9% and that of high CSF GFAP was 84.6%,
      respectively. CONCLUSION: Our data suggests that CSF IL-6 and GFAP may be useful
      early diagnostic markers of NMOSD.

PMID- 23535509
TI  - Exemestane: one part of the chemopreventive spectrum for ER-positive breast
      cancer.
AB  - Development of drugs to prevent breast cancer has focused largely on anti
      estrogenic agents, leading to approval by the US FDA of two such agents for this
      purpose: tamoxifen and raloxifene. However, the uptake of these drugs by high
      risk women and their primary care physicians has been limited, due in large part
      to a perceived unfavorable risk:benefit balance. The current focus is on
      aromatase inhibitors, which appear to have more acceptable side effects in
      addition to being more efficacious in reducing breast cancer risk in high-risk
      women. The placebo-controlled phase III MAP.3 trial tested the AI exemestane in
      high-risk women and documented a 65% relative reduction in total and a 73%
      reduction in ER-positive breast cancers in the intervention compared to the
      placebo group. Toxicities centered around musculoskeletal side effects, but in
      the relatively short 35-month median follow-up period, these did not impair
      quality-of-life. A bone study nested within MAP.3 demonstrated significant
      decreases in bone mineral density (BMD) and in structural parameters of bone
      quality. The strengths and weaknesses of preventive exemestane as evaluated in
      the MAP.3 trial are discussed as are relevant areas for future consideration:
      influence of obesity, alternative dosing, and biomarker use in phase III
      prevention trials of aromatase inhibitors.

PMID- 23535510
TI  - Perceptions and needs of women with metastatic breast cancer: a focus on clinical
      trials.
AB  - Many patients are living longer with Metastatic Breast Cancer (MBC) than ever
      before. However, complete responses remain uncommon, and progression of disease
      is often inevitable. The experience of living with MBC exposes patients to a wide
      variety of clinical, psychological, social and spiritual issues. Although much
      research effort has focused on decision-making and coping strategies among women
      with early breast cancer, relatively little attention has been given to the
      needs, experiences, and perceptions of women living with MBC. Furthermore, there
      are major research gaps in understanding and prioritizing the types of psycho
      social interventions that would make the most difference in the lives of these
      patients. Fortunately, the tide is turning. This communication represents a joint
      effort of the Breast International Group and the National Cancer Institute (NCI)
      sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions
      and needs of patients living with MBC and current obstacles facing them, and
      recommends strategies for better addressing some of these unmet needs.

PMID- 23535511
TI  - Platelet concentrates, from whole blood or collected by apheresis?
AB  - Platelet concentrates can be isolated from donated whole blood with the platelet
      rich plasma-method or the buffy coat-method. Alternatively, platelets can be
      obtained by apheresis, harvesting the platelets but returning all other cells to
      the donor. The quality and characteristics of platelets during storage are
      affected by a number of factors, such as anticoagulant, centrifugation and
      processing after collection, and pre- or post storage pooling, but when comparing
      literature on the various methods, most differences balance out. To have
      sufficient platelets to treat an adult patient, whole-blood-derived platelet
      concentrates need pooling of multiple donations, thereby increasing the risk of
      infectious agent transmission at least two-fold as compared with apheresis units.
      Allo immunization rates, acute reaction rates, and transfusion related acute lung
      injury rates are not different. Apheresis donation procedures have fewer adverse
      events. All these factors need to be considered and weighed when selecting a
      method of platelet collection for a blood center.

PMID- 23535512
TI  - Ecological effectiveness of French grassland agri-environment schemes for
      farmland bird communities.
AB  - Agri-environment schemes (AES) have been implemented to cope with the loss of
      farmland biodiversity due to agricultural intensification over the last decades.
      In France, grassland measures (more closely linked to extensive grazing) are the
      most widely implemented within the French AES, and are presumably those whose
      effectiveness can be better assessed. In this paper, we have evaluated the
      effectiveness of French grassland agri-environmental measures (gAES) to enhance
      farmland bird diversity on a national scale, using local abundances of 19
      farmland breeding birds within 463 Small Agricultural Regions (SAR) covering
      France during 2001-2008. We modeled responses of species abundances and estimated
      species richness to five categories of grassland AES, accounting for the
      characteristics of local production systems. Extensive management of grasslands
      had a positive effect on species richness. Despite mixed results on the
      effectiveness of the different grassland AES categories, our results are
      optimistic in terms of the ability of some French AES to provide benefits to
      birds. It seems that some grassland AES have achieved their objectives while
      meeting species ecological requirements. Moreover, this study highlights the fact
      that some of these grassland AES have the potential to enhance the population
      dynamics of declining species. Finally, although they all aim at benefitting
      biodiversity, it cannot be assumed that grassland measures lead to uniform
      conservation benefits.

PMID- 23535513
TI  - Use of stabilized bottom ash for bound layers of road pavements.
AB  - This paper reports about the lab scale results obtained by using stabilized
      bottom ash (SBA) from an Italian municipal solid waste incinerator as aggregates
      in cement-bound mixes and asphalt concretes for road pavements. The investigation
      focused on SBA content. From the road construction point of view, performance
      related to compaction, volumetric and mechanical properties were assessed. The
      environmental aspects were investigated performing leaching tests. The results
      suggested that SBA satisfied the environmental Italian law for reuse of non
      hazardous waste but affected significantly the stress-strain behavior of the
      final products. Therefore a maximum percentage of 10% was suggested.

PMID- 23535514
TI  - The effect of non-covalent functionalization on the thermal conductance of
      graphene/organic interfaces.
AB  - The intrinsic interfacial thermal resistance at graphene/organic interfaces, as a
      result of mismatches in the phonon vibrational spectra of the two materials,
      diminishes the overall heat transfer performance of graphene/organic
      nanocomposites. In this paper, we use molecular dynamics (MD) simulations to
      design alkyl-pyrene molecules that can non-covalently functionalize graphene
      surfaces in contact with a model organic phase composed of octane. The alkyl
      pyrene molecules possess phonon-spectra features of both graphene and octane and,
      therefore, can serve as phonon-spectra linkers to bridge the vibrational mismatch
      at the graphene/octane interface. In support of this hypothesis, we find that the
      best linker candidate can enhance the out-of-plane graphene/organic interfacial
      thermal conductance by ~22%, attributed to its capability to compensate the low
      frequency phonon mode of graphene. We also find that the length of the alkyl
      chain indirectly affects the interfacial thermal conductance through different
      orientations of these chains because they dictate the contribution of the out-of
      plane high-frequency carbon-hydrogen bond vibrations to the overall phonon
      transport. This study advances our understanding of the less destructive non
      covalent functionalization method and design principles of suitable linker
      molecules to enhance the thermal performance of graphene/organic nanocomposites
      while retaining the intrinsic chemical, thermal, and mechanical properties of
      pristine graphene.

PMID- 23535515
TI  - More than a third of GPs on commissioning groups have conflicts of interest, BMJ
      investigation shows.

PMID- 23535516
TI  - Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of
      local and systemic responses to myocardial ischemia/reperfusion.
AB  - The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal
      transducers and activators of transcription (STAT) pathways have been shown to
      play a cardioprotective role. We previously gave evidence that melanocortins
      afford cardioprotection in conditions of myocardial ischemia/reperfusion. Here we
      aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling
      in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion.
      Ischemia was produced in rats by ligature of the left anterior descending
      coronary artery for 30 min. At the end of the 2-h reperfusion, western blot
      analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3
      and pSer-STAT3, the inflammatory mediator tumor necrosis factor-alpha (TNF
      alpha), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the
      anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme
      oxygenase-1 (HO-1), was performed in the left ventricle and spleen. Intravenous
      treatment, during coronary artery occlusion, with the melanocortin analogs
      [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) and
      adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up
      regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in
      pJNK and TNF-alpha levels; these effects of NDP-alpha-MSH and ACTH-(1-24) were
      associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and
      marked decrease of the myocardial infarct size. Melanocortin treatment did not
      affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels. In the
      spleen, NDP-alpha-MSH and ACTH-(1-24) induced similar effects on the expression
      of the above transcription factors/proteins, except for pERK1/2 (down-regulated)
      and HO-1 (unaffected). Blockade of JAK and ERK pathways with AG490 and U0126,
      respectively, abrogated the myocardial infarct size reduction by NDP-alpha-MSH.
      These results indicate that melanocortins inhibit local and systemic inflammatory
      and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion,
      with consequent reduction in myocardium infarct size, seemingly via activation of
      the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling
      pathway.

PMID- 23535517
TI  - Retraction: Sasidharan et al. Evaluation of the hepatoprotective effects of
      lantadene A, a pentacyclic triterpenoid of Lantana plants against acetaminophen
      induced liver damage. Molecules 2012, 17, 13937-13947.
AB  - A recent Comment by M. Sharma published in the journal Molecules [1] raises
      issues with our previously published paper [2]. After reviewing its content, and
      although we respectfully stand by our experimental description whereby we were
      able to prepare stock and working solutions of the substance being tested, the
      arguments presented do raise concerns about the true identity of the compound
      actually used and hence the results and conclusions of our paper.

PMID- 23535518
TI  - Phenylmethimazole suppresses dsRNA-induced cytotoxicity and inflammatory
      cytokines in murine pancreatic beta cells and blocks viral acceleration of type 1
      diabetes in NOD mice.
AB  - Accumulating evidence supports a role for viruses in the pathogenesis of type 1
      diabetes mellitus (T1DM). Activation of dsRNA-sensing pathways by viral dsRNA
      induces the production of inflammatory cytokines and chemokines that trigger beta
      cell apoptosis, insulitis, and autoimmune-mediated beta cell destruction. This
      study was designed to evaluate and describe potential protective effects of
      phenylmethimazole (C10), a small molecule which blocks dsRNA-mediated signaling,
      on preventing dsRNA activation of beta cell apoptosis and the inflammatory
      pathways important in the pathogenesis of T1DM. We first investigated the
      biological effects of C10, on dsRNA-treated pancreatic beta cells in culture.
      Cell viability assays, quantitative real-time PCR, and ELISAs were utilized to
      evaluate the effects of C10 on dsRNA-induced beta cell cytotoxicity and
      cytokine/chemokine production in murine pancreatic beta cells in culture. We
      found that C10 significantly impairs dsRNA-induced beta cell cytotoxicity and up
      regulation of cytokines and chemokines involved in the pathogenesis of T1DM,
      which prompted us to evaluate C10 effects on viral acceleration of T1DM in NOD
      mice. C10 significantly inhibited viral acceleration of T1DM in NOD mice. These
      findings demonstrate that C10 (1) possesses novel beta cell protective activity
      which may have potential clinical relevance in T1DM and (2) may be a useful tool
      in achieving a better understanding of the role that dsRNA-mediated responses
      play in the pathogenesis of T1DM.

PMID- 23535519
TI  - Pathogenesis and management of retrograde type A aortic dissection after thoracic
      endovascular aortic repair.
AB  - BACKGROUND: Retrograde type A aortic dissection is a feared complication of
      thoracic aortic endografting. The aim of this study was to review the incidence,
      etiology, and management of this life-threatening complication. METHODS: A
      retrospective analysis of the literature in the last 10 years was performed. Data
      on retrograde type A aortic dissection from this literature search, along with
      authors' personal experience, provided the basis for this review. RESULTS: The
      incidence of retrograde type A aortic dissection ranges from 1.3% to 6.8%. In is
      most commonly associated with endografting of acute or chronic aortic dissection.
      Up to one third of patients will have this complication 3 months or later after
      the index procedure. Open surgical repair remains the "gold standard" for
      retrograde type A aortic dissection, although medical and endovascular approaches
      may be utilized in selected patients with prohibitive operative risk. Mortality
      remains high ranging from 20% to 57%. Potential etiologies of retrograde type A
      aortic dissection include aortic injury from catheter and wire or stent graft
      manipulation, poor perioperative antihypertensive control, inappropriate patient
      and device selection, aggressive balloon dilation, and stent graft oversizing.
      CONCLUSIONS: Retrograde type A aortic dissection remains a deadly complication of
      thoracic aortic endografting. The high incidence of delayed type A aortic
      dissection underscores the importance of imaging follow-up in patients undergoing
      a thoracic endograft procedure.

PMID- 23535520
TI  - Removal of an infected aortic endograft and open aortic reconstruction: technical
      remarks.
AB  - Infection of an aortic endoprosthesis is a potentially lethal complication of an
      endovascular abdominal aortic aneurysm repair (EVAR). Surgical treatment usually
      involves excision of the infected endograft and vascular reconstruction, either
      in-line or extraanatomic. We present a case of severe infection of an endograft
      with suprarenal fixation. The one-stage procedure describes an in-line aortic
      reconstruction using a hybrid allograft composed of cryopreserved segments of
      cadaveric thoracic aorta and superficial femoral vein. A novel device for the
      removal of suprarenal fixating struts is described, as well as other technical
      maneuvers related to the removal of the struts used by surgeons in the community.
      The technique and surgical approach should be individualized based on patient
      characteristics, preoperative imaging, and knowledge of endograft construction. 

PMID- 23535521
TI  - Contemporary vascular smartphone medical applications.
AB  - BACKGROUND: Use of smartphones and medical mHealth applications (apps) within the
      clinical environment provides a potential means for delivering elements of
      vascular care. This article reviews the contemporary availability of apps
      specifically themed to major vascular diseases and the opportunities and concerns
      regarding their integration into practice. METHODS: Smartphone apps relating to
      major vascular diseases were identified from the app stores for the 6 most
      popular smartphone platforms, including iPhone, Android, Blackberry, Nokia,
      Windows, and Samsung. Search terms included peripheral artery (arterial) disease,
      varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers,
      hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic
      disorders. RESULTS: Forty-nine vascular-themed apps were identified. Sixteen
      (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings,
      but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical
      professional involvement in their design or content. CONCLUSIONS: The integration
      of apps into the delivery of care has the potential to benefit vascular health
      care workers and patients. However, high-quality apps designed by clinicians with
      vascular expertise are currently lacking and represent an area of concern in the
      mHealth market. Improvement in the quality and reliability of these apps will
      require the development of robust regulation.

PMID- 23535522
TI  - Novel suture technique for hemostatic aortic anastomosis: backstitch.
AB  - Postoperative anastomotic suture line complications, such as hemorrhage and
      pseudoaneurysm, are often encountered in thoracic aortic surgery. To minimize
      these complications different anastomotic techniques have been developed. We
      hereby describe a new distal anastomotic technique, which involves positioning
      the graft inside the aorta at the distal end, reinforcing the suture line with an
      externally placed Teflon felt strip, and finishing the anastomosis with a
      circumferential and continued suture technique called "backstitch." 

PMID- 23535523
TI  - In-stent restenosis in the superficial femoral artery.
AB  - As the number of endovascular peripheral arterial interventions is increasing
      nationwide, so is the rate of observed in-stent restenosis, specifically in the
      superficial femoral artery. A paucity of literature is available regarding the
      pathophysiology, risk factors, and therapies associated with in-stent restenosis
      of the superficial femoral artery. This article summarizes the accumulated
      knowledge on these topics and sheds some light on the prospects for future
      therapies.

PMID- 23535524
TI  - Perioperative approach in the surgical management of carotid body tumors.

PMID- 23535525
TI  - Impact of adding aspirin to beta-blocker and statin in high-risk patients
      undergoing major vascular surgery.
AB  - BACKGROUND: Beta-blockers (BB) and statins (S) independently have been shown to
      reduce perioperative mortality and myocardial infarction (MI) in patients
      undergoing vascular surgery. In this study we evaluated the benefits of adding
      aspirin (A) to BB and S (ABBS), with/without angiotensin-converting enzyme
      inhibitor (ACE-I) on postoperative outcome in high-risk patients undergoing major
      vascular surgery. METHODS: Analysis of consecutive patients undergoing elective
      vascular surgery at the University of Michigan Cardiovascular Center was
      performed. Univariate and multivariate analyses were done using cardiac risk
      index [Revised Cardiac Risk Index (RCRI), coronary artery disease (CAD), insulin
      dependent diabetes mellitus (IDDM), cerebral vascular disease, renal dysfunction,
      congestive heart failure, and major surgery]; pulmonary disease; and A, BB, S
      (ABBS)+/-ACE-I use. Baseline clinical characteristics and medication were
      adjusted using propensity scores. Endpoints were bleeding, 30-day MI, stroke, and
      12-month mortality. RESULTS: Between 2003 and 2010, 4,149 arterial procedures
      were performed, 819 of which were risk stratified as RCRI>=3. The incidence of MI
      was 3-fold lower (2.5% vs. 7.8%, OR 0.31, 95% CI 0.15-0.61, P=0.001) in ABBS+/
      ACE-I (n=513) as compared with non-ABBS+/-ACE-I (n=306). The 12-month mortality
      was 8-fold lower in ABBS+/-ACE-I as compared non-ABBS+/-ACE-I (5.9% vs. 37.5%, HR
      0.13, 95% CI 0.08-0.20, P<0.0001). After adjustment for the propensity to use
      various therapies, A (HR 0.35, 95% CI 0.24-0.53, P<0.0001), BB (HR 0.65, 95% CI
      0.43-1.0, P=0.05), and S (HR 0.36, 95% CI 0.25-0.53, P<0.0001) remained
      associated with improved 12-month survival. ACE-I use (HR 0.80, 95% CI 0.54-1.19,
      P=0.27) was not predictive. Aspirin did not predict severe/moderate bleeding.
      CONCLUSIONS: In high-risk patients undergoing major vascular surgery, ABBS
      therapy has superior 30-day and 12-month risk reduction benefits for MI, stroke,
      and mortality as compared with A, BB, or S independently. ACE-I did not
      demonstrate additional risk-reduction benefits.

PMID- 23535526
TI  - Thoracic aortic aneurysm with aortic pseudocoarctation involving the left
      subclavian artery.
AB  - A 39-year-old man with a thoracic aortic aneurysm and pseudocoarctation underwent
      graft replacement of the distal arch. The left subclavian artery, which rose just
      after the aneurysm, was also reconstructed at surgery. The aneurysmal wall was
      extremely thin, and the adventitia and a small amount of medial tissue were found
      on histologic examination. Thus, surgical treatment was recommended due to risk
      of rupture. Furthermore, because aneurysms involved the cervical branch, separate
      reconstruction was also performed. Endovascular intervention is not appropriate
      for this group of patients because of the complex kinking of the aorta and the
      extremely thin aneurysmal wall. 

PMID- 23535527
TI  - Adenovirus infections in heart transplantation.
AB  - Adenovirus infections have been associated with significant morbidity and
      mortality in immunocompromised hosts. The clinical significance of adenovirus
      disease in heart transplantation is not well-defined; in particular, the
      significance of adenovirus identification in myocardium remains unclear. Although
      severe adenovirus disease has been described in heart transplant recipients,
      adenovirus infections seem to be more frequently associated with increased risk
      of adverse cardiac events, such as rejection, ventricular dysfunction, coronary
      vasculopathy, need for retransplantation, and graft loss because of death.
      Cidofovir is currently considered the standard of treatment for adenovirus
      disease not responding to reduction of immunosuppression.

PMID- 23535528
TI  - An office-based approach to emotional and behavioral risk factor reduction for
      cardiovascular disease.
AB  - There are many psychological risk factors for cardiovascular disease, and the
      ability to reduce mortality depends on an ability to integrate care of these risk
      factors with traditional Framingham cardiovascular risk and use them both in
      routine practice. The aim of this article is to provide an update of all the
      major emotional and behavioral cardiovascular risk factors along with a practical
      treatment model for implementation. First, we provide a review of major emotional
      and behavioral cardiovascular risk factors, the associated primary effect, and
      proposed mechanism of action. Second, we provide an office-based approach to
      cardiovascular risk factor reduction and methods of reducing barriers to
      implementation, called Prevention Oriented Primary Care-Abridged. The approach
      integrates several forms of detection, assessment using the 3As (ask, assess,
      assist), and Stages of Change approaches, and subsequent efficient and targeted
      treatment with either Motivational Interviewing or further office intervention. A
      case example is provided to help illustrate this process. 

PMID- 23535529
TI  - Music therapy in cardiac health care: current issues in research.
AB  - Music therapy is a service that has become more prevalent as an adjunct to
      medical practice-as its evidence base expands and music therapists begin to join
      the cardiology team in every phase of care, from the most serious cases to those
      maintaining good heart health. Although applications of music medicine, primarily
      listening to short segments of music, are capable of stabilizing vital signs and
      managing symptoms in the short-term, music therapy interventions by a qualified
      practitioner are showing promise in establishing deeper and more lasting impact.
      On the basis of mind-body approaches, stress/coping models, the neuromatrix
      theory of pain, and entrainment, music therapy capitalizes on the ability of
      music to affect the autonomic nervous system. Although only a limited number of
      randomized controlled trials pinpoint the efficacy of specific music therapy
      interventions, qualitative research reveals some profound outcomes in certain
      individuals. A depth of understanding related to the experience of living with a
      cardiovascular disease can be gained through music therapy approaches such as
      nonverbal music psychotherapy and guided imagery and music. The multifaceted
      nature of musical responsiveness contributes to strong individual variability and
      must be taken into account in the development of research protocols for future
      music therapy and music medicine interventions. The extant research provides a
      foundation for exploring the many potential psychosocial, physiological, and
      spiritual outcomes of a music therapy service for cardiology patients. 

PMID- 23535530
TI  - Apixaban: a new factor Xa inhibitor for stroke prevention in patients with
      nonvalvular atrial fibrillation.
AB  - Atrial fibrillation (AF) is an independent risk factor for ischemic stroke
      occurrence, severity, recurrence, and mortality. Anticoagulation therapy for the
      prevention of thromboembolism is critical in patients with AF who are at risk of
      stroke. Warfarin has been an efficacious anticoagulant for this purpose, but its
      use has been limited by frequent laboratory monitoring, drug interactions,
      unpredictable individual response, delayed onset of action, and bleeding.
      Apixaban is the second oral direct selective factor Xa inhibitor approved for the
      prevention of stroke/systemic embolism in patients with nonvalvular AF. It was
      significantly better than aspirin in reducing stroke (ischemic or hemorrhagic) or
      systemic embolism without increasing the risk of major bleeding in patients with
      AF who were at increased risk of stroke and for whom warfarin was unsuitable. In
      a randomized, double-blind trial that was originally designed to test for
      noninferiority, apixaban was superior to warfarin (target international
      normalized ratio 2-3) in preventing stroke or systemic embolism, caused less
      bleeding, and resulted in lower mortality in patients with AF. Apixaban has a
      half-life of about 12 hours, and the normal dosage is 5 mg orally twice daily.
      However, it may be reduced to 2.5 mg twice daily based on individual factors of
      the patient (age, renal function, and body weight) and the concomitant use of
      potent dual inhibitors of cytochrome P450 3A4 and P-glycoprotein. Similar to
      other novel oral anticoagulants (dabigatran and rivaroxaban), apixaban has no
      reversal agent for its anticoagulant effect. Overall, apixaban is a safe and
      efficacious alternative for stroke prophylaxis in high-risk patients who have AF
      and who are unable to achieve therapeutic goals with warfarin therapy.

PMID- 23535531
TI  - Learning and memory-related brain activity dynamics are altered in systemic lupus
      erythematosus: a functional magnetic resonance imaging study.
AB  - BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE);
      however, the pathogenesis is unknown. METHODS: We studied 12 patients with SLE
      without clinically overt neuropsychiatric manifestations and 11 matched healthy
      controls, aiming to characterize neural correlates of memory impairment, using
      structural and functional magnetic resonance imaging (MRI). The paradigm
      consisted of three encoding and free-recall cycles, allowing characterization of
      dynamics along consecutive retrieval attempts. RESULTS: During learning, patients
      with SLE and healthy controls showed brain activity changes in two principal
      networks, the default mode network (DMN) and the task-positive network (TPN).
      Patients with SLE demonstrated significantly less deactivation in the DMN and
      greater activation in the TPN, reflecting greater recruitment of both networks.
      The anterior medial prefrontal cortex (amPFC) of the DMN emerged as the only
      region where brain activity dynamics were altered both over the learning process
      (p < 0.006), and within free-recall period attempts (p < 0.034). Patients showed
      significant positive correlations between learning efficiency and hippocampal
      activity, and greater hippocampal functional connectivity, with pronounced
      connectivity to DMN structures. CONCLUSIONS: Increased brain activation in
      patients with SLE during learning may reflect compensatory mechanisms to overcome
      memory impairment. Our findings localize this impairment to the amPFC, consistent
      with the behavioral pattern seen in SLE. Altered networking of the hippocampal
      subsystem of the DMN is consistent with hippocampal neuronal damage seen in SLE,
      and may reflect compensatory cortical reorganization to cope with dysfunction in
      these regions pivotal to mnemonic functions.

PMID- 23535533
TI  - The distribution of serum folate concentration and red blood cell indices in
      alcoholics.
AB  - Chronic alcohol consumption leads to malnutrition and to the deficiency of many
      vitamins. One of the most important is folate deficiency. Folate deficiency
      disrupts the process of hematopoiesis, which can be evaluated by the changes of
      red cell indices. The aim of this study was to determine the hematological
      disturbances by the measurement of red blood cell indices in a Polish population
      of chronic alcoholics according to folate status. We studied 80 consecutive
      chronic alcoholic men and 30 healthy controls. Patients were divided into 2
      groups according to the folate concentration. The serum folate and vitamin B12
      concentration and the blood count were determined. We have shown that the serum
      folate concentration was decreased in 40% of alcoholics, but there was no folate
      deficiency and the level of vitamin B12 was normal. There was no correlation
      between folate, vitamin B12 and hematological indices. We have observed that most
      hematological parameters (Hb, RBCs, and Hct) in alcoholics were decreased and
      only two of them (MCV and MCHC) were increased in comparison with the controls.
      We observed no significant correlation between the RBCs indices and the weekly
      alcohol intake, but the correlation between RBCs, Hb, Hct and the duration of
      dependence have been shown. We concluded that, there is no folate deficiency in
      the Polish alcoholic population but the abusers with low folate levels may
      already have some RBCs indices affected. It means that the Polish alcoholic
      population consumes a sufficient amount of vitamins, which prevents the
      occurrence of hematological disturbances.

PMID- 23535532
TI  - Estradiol differentially regulates calreticulin: a potential link with abnormal T
      cell function in systemic lupus erythematosus?
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease that
      affects women nine times more often than men. The present study investigates
      estradiol-dependent control of the calcium-buffering protein, calreticulin, to
      gain further insight into the molecular basis of abnormal T cell signaling in SLE
      T cells. METHODS: T cells were purified from blood samples obtained from healthy
      females and SLE patients. Calreticulin expression was quantified by real-time
      polymerase chain amplification. Calreticulin and estrogen receptor-alpha were co
      precipitated and analyzed by Western blotting to determine if the proteins
      associate in T cells. RESULTS: Calreticulin expression increased (p = 0.034) in
      activated control T cells, while estradiol decreased (p = 0.044) calreticulin in
      resting T cells. Calreticulin expression decreased in activated SLE T cell
      samples and increased in approximately 50% of resting T cell samples. Plasma
      estradiol was similar (p > 0.05) among SLE patients and control volunteers.
      Estrogen receptor-alpha and calreticulin co-precipitated from nuclear and
      cytoplasmic T cell compartments. CONCLUSIONS: The results indicate that estradiol
      tightly regulates calreticulin expression in normal human T cells, and the
      dynamics are different between activated and resting T cells. The absence of this
      tight regulation in SLE T cells could contribute to abnormal T cell function.

PMID- 23535534
TI  - Contents of all forms of vitamin B6, pyridoxine-beta-glucoside and 4-pyridoxic
      acid in mature milk of Japanese women according to 4-pyridoxolactone-conversion
      high performance liquid chromatography.
AB  - The contents of six vitamin B6 forms, pyridoxine-beta-glucoside, and 4-pyridoxic
      acid in mature milk of 20 Japanese lactating women consuming ordinary Japanese
      foods were determined by a 4-pyridoxolactone-conversion HPLC method. These
      compounds were determined with the average recovery rate of 83.9% or more. The
      average total content of vitamin B6 forms was 1.01 +/- 0.32 (umol/L). Pyridoxal
      and pyridoxal 5'-phosphate were found in all of the samples, and their average
      contents were 0.71 +/- 0.28 (umol/L) and 0.16 +/- 0.07 (umol/L), respectively.
      Pyridoxamine, pyridoxine, pyridoxamine 5'-phosphate, pyridoxine 5'-phosphate, and
      pyridoxine-beta-glucoside were found in 15, 14, 13, 9, and 7 samples,
      respectively. The presence of pyridoxine 5'-phosphate was for the first time
      found in human milk. A method for the determination of 4-pyridoxic acid, which is
      the excretion form of vitamin B6, was modified to quantitate it by isocratic
      HPLC. 4-Pyridoxic acid was found in all samples, and its average content was
      0.094 +/- 0.040 (umol/L), which was only 12% of its content in cow (Holstein)
      milk. The total content of vitamin B6 forms, and predominant presence of
      pyridoxal among other vitamin B6 forms in the Japanese women's milk samples
      shared similar characteristics with American women's milk samples.

PMID- 23535535
TI  - A case study on the association of variation of bitter-taste receptor gene
      TAS2R38 with the height, weight and energy intake in Japanese female college
      students.
AB  - One of the critical factors that determines individual differences in dietary
      behavior and nutritional status is the sensory-affecting quality of food, in
      particular its taste. Variation of one bitter taste receptor gene, TAS2R38, which
      is associated with the differential sensitivity to phenylthiocarbamide (PTC) and
      6-n-propylthiouracil (PROP), has been demonstrated to affect the dietary intake
      pattern. A case study was performed to examine the association of the TAS2R38
      genotypes/haplotypes with the body size (height, weight and BMI) and with the
      food and nutrient intake. Eighty-four college students, all females, with an age
      range of 18-21 y were recruited from the University of Shizuoka. The genotypes of
      two common single nucleotide polymorphisms in TAS2R38 (A49P and I296V) were
      determined by PCR-restriction fragment length polymorphism (RFLP) method. The
      height, weight and body mass index (BMI), and (in a subgroup of 47 subjects) food
      and nutrition intake estimated from 3 d of food recording, were compared between
      homozygotes for the PTC/PROP-nontaster haplotype (AI haplotype) and carriers with
      the PTC/PROP-taster haplotype (PV haplotype). The results show that the
      homozygotes with AI haplotype were taller and heavier than the carriers of PV
      haplotype, while BMI values were similar between them. The former group also had
      higher energy and carbohydrate intakes than the latter group. Neither vegetable
      nor dairy product intake was different between the homozygotes with AI haplotype
      and the carriers of PV haplotype. In conclusion, the PTC/PROP-nontaster TAS2R38
      genotype/haplotype was associated with height and weight but not with BMI, which
      may in turn have influenced the energy and carbohydrate intakes.

PMID- 23535536
TI  - How does fortification affect the distribution of calcium and vitamin B1 intake
      at the school lunch for fifth-grade children?
AB  - The purpose of this study was to estimate the usual intake distribution of
      calcium and vitamin B(1) of fifth-grade children based on a 3-d dietary survey
      and to assess nutrient intake using Dietary Reference Intakes (DRIs 2010). A
      cross-sectional study was undertaken from October 2007 to February 2008 in
      schools located in Tokyo and Okayama, Japan. A total of 94 fifth-grade children
      attending 5 elementary schools participated in the study. The weighed plate waste
      method and observation were used to collect data on the school lunches and
      dietary records by children, accompanied by photographs used to collect data on
      meals at home. The study lasted 3 d, 2 non-consecutive days with school lunches
      and 1 d without. The estimated proportion of subjects below the Estimated Average
      Requirement (EAR) for calcium intake with milk in the school lunch decreased by
      40% compared to the calcium intake without milk in the school lunch. Vitamin B1
      intake from less than 0.45 mg/1,000 kcal fortified rice was estimated to be 0%.
      The intake distribution of calcium has increased by 150 mg by taking milk and the
      intake distribution of vitamin B1 has increased 0.20 mg by taking fortified rice
      in the school lunch. Calcium and vitamin B1 intake in the school lunch has
      changed the distribution of calcium and vitamin B1 intake upward, and decreased
      the number of estimated subjects that were below EAR. However, the distribution
      was not shifted across the board and the shape of the distribution has changed.

PMID- 23535537
TI  - The effect of different amounts of calcium intake on bone metabolism and arterial
      calcification in ovariectomized rats.
AB  - Low calcium (Ca) intake is the one of risk factors for both bone loss and medial
      elastocalcinosis in an estrogen deficiency state. To examine the effect of
      different amounts of Ca intake on the relationship between bone mass alteration
      and medial elastocalcinosis, 6-wk-old female SD rats were randomized into
      ovariectomized (OVX) control or OVX treated with vitamin D(3) plus nicotine
      injection (VDN) groups. The OVX treated with VDN group was then divided into 5
      groups depending on the different Ca content in their diet, 0.01%, 0.1%, 0.6%,
      1.2%, and 2.4% Ca intakes. After 8 wk of experimentation, the low Ca intake
      groups of 0.01% and 0.1% showed a low bone mineral density (BMD) and bone
      properties significantly different from those of the other groups, whereas the
      high Ca intake groups of 1.2% and 2.4% showed no difference compared with the OVX
      control. Only in the 0.01% Ca intake group, a significantly higher Ca content in
      the thoracic artery was found compared with that of the OVX control. Arterial
      tissues of the 0.01% Ca intake group showed an increase of bone-specific alkaline
      phosphatase (BAP) activity, a marker of bone mineralization, associated with
      arterial Ca content. However, the high Ca intake did not affect arterial Ca
      content nor arterial BAP activity. These results suggested that a low Ca intake
      during periods of rapid bone loss caused by estrogen deficiency might be one
      possible cause for the complication of both bone loss and medial
      elastocalcinosis.

PMID- 23535538
TI  - Influence of dietary macronutrients on induction of hepatic drug metabolizing
      enzymes by Coleus forskohlii extract in mice.
AB  - From studies in mice, we have reported that Coleus forskohlii extract (CFE), a
      popular herbal weight-loss ingredient, markedly induced hepatic drug metabolizing
      enzymes, especially cytochrome P450 (CYP), and interacted with co-administered
      drugs. This study was designed to examine how the induction of drug metabolizing
      enzymes by CFE was influenced by different levels of macronutrients in the diet.
      Mice were fed a non-purified diet or semi-purified diet with and without CFE (0.3
      0.5%) for 14-18 d, and changes in the ratio of liver weight to body weight, an
      indicator of hepatic CYP induction, and hepatic drug metabolizing enzymes were
      analyzed. The ratio of liver weight to body weight, content and activities of
      CYPs, and activity of glutathione S-transferase were higher in a semi-purified
      standard diet (AIN93G formula) group than in high sucrose (62.9%) and high fat
      (29.9%) diet groups. Different levels of protein (7%, 20%, and 33%) in the diets
      did not influence CFE-induced CYP induction or increase the ratio of liver weight
      to body weight. The effect of CFE on the ratio of liver weight to body weight was
      higher with a semi-purified diet than with a non-purified diet, and was similar
      between dietary administration and intragastric gavage when the CFE dose and the
      diet were the same. There was a positive correlation between CFE-induced CYP
      induction and the content of starch in the diets, suggesting that dietary starch
      potentiates CFE-induced CYP induction in mice. The mechanism of enhanced CYP
      induction remains unclear.

PMID- 23535539
TI  - Adverse effects of excessive leucine intake depend on dietary protein intake: a
      transcriptomic analysis to identify useful biomarkers.
AB  - The present study was conducted to identify reliable gene biomarkers for the
      adverse effects of excessive leucine (Leu) in Sprague-Dawley rats by DNA
      microarray. It has long been known that the adverse effects of excessive amino
      acid intake depend on dietary protein levels. Male rats were divided into 12
      groups (n=6) and fed for 1 wk a diet containing low (6%), moderate (12%) or high
      (40%) protein. Different levels of Leu (0, 2, 4, and 8%) were added to the diets.
      Consumption of diets containing more than 4% Leu in 6% protein resulted in growth
      retardation and reduced liver weight, whereas the administration of the same dose
      of Leu with 12% or 40% protein did not affect them. By a process of systematic
      data extraction, 6 candidate gene markers were identified. The liver gene
      expression data obtained from another experiment with 0, 2, 3, 4, and 8% Leu in a
      low-protein diet was used to examine the validity of these biomarker candidates
      with receiver operating characteristic (ROC) curve analysis. All of AUC values of
      the biomarker candidates were more than 0.700, suggesting the effectiveness of
      the marker candidates as the indices of Leu excess. The cut-off value for the ROC
      curve of the gene-marker panel, which was obtained by multiple regression
      analysis of gene markers, indicated that Leu levels higher than 3% have adverse
      effects. In conclusion, the gene-marker panel suggested that for male rats
      dietary Leu supplementation of 2% is the NOAEL dose in low-protein (6%) diets.

PMID- 23535540
TI  - Intragastric administration of allyl isothiocyanate reduces hyperglycemia in
      intraperitoneal glucose tolerance test (IPGTT) by enhancing blood glucose
      consumption in mice.
AB  - We investigated the effects of allyl isothiocyanate (AITC) on the blood glucose
      levels of mice using an intraperitoneal glucose tolerance test. The intragastric
      administration of 25 mg/kg body weight AITC reduced the increase in blood glucose
      level after 2 g/kg body weight glucose was given intraperitoneally, compared with
      that of control mice. To elucidate the mechanism responsible for the reduction,
      respiratory gas analysis employing (13)C-labeled glucose was performed. The
      intragastrically administering AITC increased (13)CO2 emission, compared to
      vehicle, after intraperitoneal administration of (13)C-labeled glucose. This
      indicated that AITC increased the utilization of exogenously administered
      glucose, which was excessive glucose in the blood. To examine whether transient
      receptor potential (TRP) channels mediated this reduction in the blood glucose
      levels, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastrically
      administering AITC reduced the increase in the blood glucose level in TRPA1 KO
      mice but not in TRPV1 KO mice. These findings suggest that dietary AITC might
      reduce the increases in blood glucose levels by increasing the utilization of
      excessive glucose in the blood by activating TRPV1.

PMID- 23535541
TI  - alpha-Tocopherol status and expression of alpha-tocopherol transfer protein in
      type 2 diabetic Goto-Kakizaki rats.
AB  - Vitamin E, a critical fat-soluble vitamin antioxidant, is expressed on cell
      membranes and prevents propagation of lipid peroxidation. alpha-Tocopherol
      transfer protein (alpha-TTP) is a cytosolic protein located in the hepatocytes
      that acts as the principal regulator of the circulating alpha-tocopherol levels.
      Type 2 diabetes is a metabolic disorder characterized by hyperglycemia, caused by
      insulin resistance. Lipid peroxidation promotes the clinical progression and
      development of complications in type 2 diabetes. Results of animal and human
      experiments on the vitamin E status in diabetes are conflicting. The present
      study was conducted with the objective of investigating the vitamin E status and
      alpha-TTP expression in Goto-Kakizaki (GK) rats, a model of type 2 diabetes. In
      diabetic GK rats, increases of the alpha-tocopherol levels in the plasma and
      liver were observed as compared with the levels in the controls. No alternation
      in the CuZn-superoxide dismutase (SOD) or Mn-SOD gene expression was found in the
      liver of GK rats as compared with that in the controls. The GK rats showed an
      increase of the hepatic expression of the alpha-TTP gene as compared with the
      level in the controls. It can be suggested that the increased hepatic alpha-TTP
      gene expression levels may influence plasma alpha-tocopherol levels in the
      diabetic animals. Hence, investigation of the regulatory factors of alpha-TTP
      expression may provide important clues to highlighting the antioxidant mechanisms
      of vitamin E.

PMID- 23535542
TI  - Selenium uptake by edible oyster mushrooms (Pleurotus sp.) from selenium
      hyperaccumulated wheat straw.
AB  - In an effort to produce selenium (Se)-fortifying edible mushrooms, five species
      of oyster mushroom (Pleurotus sp.), were cultivated on Se-rich wheat straw
      collected from a seleniferous belt of Punjab, India. Total selenium was analyzed
      in the selenium hyperaccumulated wheat straw and the fruiting bodies.
      Significantly high levels (p<0.0001) of Se uptake were observed in fruiting
      bodies of all mushrooms grown on Se-rich wheat straw. To the best of our
      knowledge, accumulation and quantification of selenium in mushrooms has hitherto
      not been reported with substrates naturally enriched with selenium. The results
      demonstrate the potential of selenium-rich agricultural residues as substrates
      for production of Se-enriched mushrooms and the ability of different species of
      oyster mushrooms to absorb and fortify selenium. The study envisages potential
      use of selenium-rich agricultural residues towards cultivation of Se-enriched
      mushrooms for application in selenium supplementation or neutraceutical
      preparations.

PMID- 23535543
TI  - High incidence of lipid deposition in the liver of rats fed a diet supplemented
      with branched-chain amino acids under vitamin B6 deficiency.
AB  - Male Wistar rats were fed four diets composed of purified 20% vitamin-free casein
      diet with (+) or without (-) vitamin B(6) (7.0 mg of pyridoxine HCl/kg of diet)
      and with (+) or without (-) branched-chain amino acids (BCAAs) of valine,
      leucine, and isoleucine (4.75%): B(6)(+)BCAA(-); B(6)(+)BCAA(+); B(6)(-)BCAA(-);
      and B(6)(-)BCAA(+) for 21 d. Among rats fed the B(6)(-)BCAA(+) diet, about a half
      showed lipid deposition in the liver. On the other hand, serum triacylglycerol
      levels in the B(6)(-)BCAA(+) group tended to be decreased. Hepatic
      triacylglycerol and cholesterol levels tended to increase in the B(6)(-)BCAA(+)
      group compared with the other three groups. Serum apolipoprotein B and
      apolipoprotein E (apo E) levels in the B(6)(-)BCAA(+) group were the lowest among
      the three groups. In contrast, hepatic apo E levels in the B(6)(-)BCAA(+) group
      were the highest among the three groups. High-performance liquid chromatography
      of pooled serum of rats with lipid deposits revealed that triacylglycerol and
      cholesterol levels in very low-density lipoprotein (VLDL) were decreased compared
      with other diet groups. These results strongly suggest that one of the mechanisms
      of lipid deposition in rats fed a B(6)(-)BCAA(+) diet is due to impaired
      secretion of VLDL.

PMID- 23535545
TI  - [Tumor screening].

PMID- 23535544
TI  - Protective efficacy of orally administered, heat-killed Lactobacillus pentosus
      b240 against influenza A virus.
AB  - Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century.
      Although various probiotic Lactobacillus species have been shown to have anti
      microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy
      and mechanisms behind their protection remain largely unknown. Here, we evaluated
      the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against
      lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define
      the protective responses induced by b240, we performed virologic,
      histopathologic, and transcriptomic analyses on the mouse lungs. Although we did
      not observe an appreciable effect of b240 on virus growth, cytokine production,
      or histopathology, gene expressional analysis revealed that oral administration
      of b240 differentially regulates antiviral gene expression in mouse lungs. Our
      results unveil the possible mechanisms behind the protection mediated by b240
      against influenza virus infection and provide new insights into probiotic
      therapy.

PMID- 23535546
TI  - [Cancer screening - principles, evaluation and implementation].
AB  - Screening for malignant disease aims to reduce the population risk of impaired
      health due to the tumor in question. Screening does not only entail testing but
      covers all steps required to achieve the intended reduction in risk, from the
      appropriate information of the population to a suitable therapy. Screening tests
      are performed in individuals free or unaware of any symptoms associated with the
      tumor. An essential condition is a recognizable pathological abnormality, which
      occurs without symptoms and represents a pre-clinical, early stage of the tumor.
      Overdiagnosis and overtreatment have only recently been recognized as important
      problems of screening for malignant disease. Overdiagnosis is defined as a
      screening-detected tumor that would never have led to symptoms. In prostate
      specific antigen (PSA) screening for prostate cancer 50 % - 70 % of screening
      detected cancers represent such overdiagnoses. Similarly, in the case of
      mammography screening 20 % - 30 % of screening-detected breast cancers are
      overdiagnoses. The evaluation of screening interventions is often affected by
      biases such as healthy screenee effects or length and lead time bias. Randomized
      controlled trials are therefore needed to examine the efficacy and effectiveness
      of screening interventions and to define the rate of adverse outcomes such as
      unnecessary diagnostic evaluations, overdiagnosis and overtreatment.
      Unfortunately there is no independent Swiss body comparable to the National
      Screening Committee in the United Kingdom or the United States Preventive
      Services Task Force, which examines screening tests and programs and develops
      recommendations. Clearly defined goals, a central organization responsible for
      inviting eligible individuals, documentation and quality assurance and balanced
      information of the public are important attributes of successful screening
      programs. In Switzerland the establishment of such programs is hampered by the
      highly fragmented, Federal health system which allows patients to access
      specialists directly.

PMID- 23535547
TI  - [Mammography screening].
AB  - Breast cancer screening using mammography is one of the few screening
      interventions that have been assessed in several large randomized controlled
      studies (RCTs). Results from eight RCTs are available and have been summarized in
      several systematic reviews and meta-analyses, most of which conclude that
      mammography screening achieve a relative reduction in breast cancer mortality of
      20 %. In the Swiss context this translates to one prevented breast cancer death
      over 10 years among 1000 women who start biannual mammography screening at age
      50. However, mammography screening leads to the detection of cancers that would
      never have been found were it not for the screening (overdiagnosis). Screening
      thus increases the incidence of breast cancer, by about 20 %, which in turn leads
      to more therapies (surgery, radiation and chemotherapy). Over ten years after
      starting mammography at age 50, four additional women out of 1000 will be
      diagnosed with breast cancer. Without screening, these women would not have had a
      diagnosis. Over the same ten years (five screening rounds), about one in five
      women will have at least one mammography result which requires further diagnostic
      workup. Furthermore, even when mammography screening is implemented, 20 to 30 %
      breast cancer patients will not be diagnosed by the screening but between
      screening rounds. The information and knowledge of the population about benefits
      and harms of mammography screening is inadequate in that the benefits are
      overestimated and the harms underestimated. The female population needs to be
      better informed on both these aspects of mammography screening. Women have a
      right to receive adequate evidence-based information in order to make an informed
      decision whether to attend mammography screening.

PMID- 23535548
TI  - [Screening for prostate cancer].
AB  - Prostate cancer screening has been a controversial for decades. The recently
      published findings of large trials have further intensified the debate. The
      prospect of reducing mortality from prostate cancer is measured against the risk
      of over-diagnosing the disease. In individual cases, the trade-off between
      possible benefits and harms is possible to ascertain, so general recommendations
      in favor of or against PSA tests for individuals cannot be made. The majority of
      men, however, are not well-informed on the possible advantages and drawbacks of
      screening. This situation urgently needs to be corrected. The PSA test is
      promoted to healthy men, who need to be provided with especially detailed
      information. If not provided with clear and unbiased information on the risks
      associated with the test (above all over-diagnosis and over-treatment), these men
      cannot be considered to be fully informed.

PMID- 23535549
TI  - [Cervical cancer screening in Switzerland - current practice and future
      challenges].
AB  - At the beginning of the 20th Century, cervical cancer was the leading cause of
      death from cancer in women. A marked decline in cervical cancer has been observed
      since the 1960s, in parallel with the introduction of the Papanicolau (Pap) test
      as a cytological screening method. Today, Pap smear screening is still the most
      widely used tool for cervical cancer prevention. Testing for human papillomavirus
      (HPV) in cervical specimens or a combination of Pap and HPV testing are also now
      available. In this article we compare current guidelines for cervical cancer
      screening in Switzerland with those in other European countries. In view of the
      opportunities offered by HPV testing and, since 2008, HPV vaccination, current
      guidelines for cervical cancer screening should be updated. Both the choice of
      screening tests and general organization of cervical cancer screening should be
      reviewed.

PMID- 23535550
TI  - [Colorectal cancer screening].
AB  - One of the most common cancers, colorectal cancer is a leading cause of cancer
      deaths worldwide. The vast majority of colorectal carcinomas develop slowly from
      easily-removed precursors (adenomas), and in contrast to most other types of
      cancer, chances of prevention and early detection are very good. Tests for fecal
      occult blood, sigmoidoscopy and colonoscopy are frequently recommended and widely
      used. Most western countries have initiated population-wide screening programs
      for colorectal cancer, with the goal of greatly reducing incidence and mortality.
      Various models for screening programs and different screening examinations have
      been proposed and implemented. Evidence from a range of countries shows that the
      highest participation rates are obtained when programs are designed to invite
      eligible individuals to come in for screening.

PMID- 23535551
TI  - [Lung cancer screening - an overview about chances and risks].
AB  - Lung cancer is a leading cause of death worldwide. Patients are usually diagnosed
      at an advanced stage and have a very poor prognosis. In Switzerland, lung cancer
      is the most frequent cause of cancer death in men and the second most frequent
      cause of cancer death in women. Programmes to prevent individuals from initiating
      to smoke and to support smokers to quit are the most effective lung cancer
      prevention strategy. Whether routine screening for lung cancer in smokers is
      effective to reduce lung cancer related morbidity and mortality remains
      questionable. We summarize the evidence of five recent randomised controlled
      trials on routine screening for lung cancer in smokers. One study found no
      benefit of periodic conventional chest X-rays as compared to usual care without
      regular imaging for reducing lung cancer death. In four other trials, low-dose
      computer tomography (LDCT) was compared to conventional chest X-rays and to usual
      care. Only the largest trial, the US based National Lung Cancer Screening Trial
      (NLST), demonstrated a statistically significant reduction of lung cancer
      mortality of LDCT compared to conventional chest X-rays whereas three European
      trials could not prove any benefit. The results of the NLST need to be
      interpreted with care due to limited generalizability to European settings. LDCT
      screening had an unacceptable high rate of false positive findings resulting in
      an enormous use of resources for diagnostic work-up. Whether LDCT screening is
      associated with an acceptable incremental cost-effectiveness ratio still warrants
      further investigation.

PMID- 23535552
TI  - [Cancer screening and risk communication].
AB  - In most psychological and medical research, patients are assumed to have
      difficulties with health statistics but clinicians not. However, studies indicate
      that most doctors have problems in understanding health statistics, including
      those of their own speciality. For example, only two out of 20 urologists knew
      the information relevant for a patient to make an informed decision about whether
      to take PSA screening for prostate cancer, just 14 out of 65 physicians in
      internal medicine understood that 5-year survival rates do not tell anything
      about screening's benefit, and merely 34 out of 160 gynecologists were able to
      interpret the meaning of a positive test result. This statistical illiteracy has
      a direct effect on patients understanding and interpretation of medical issues.
      Not rarely their own limited health literacy and their doctors' misinformation
      make them suffer through a time of emotional distress and unnecessary anxiety.
      The main reasons for doctors' statistical illiteracy are medical schools that
      ignore the importance of teaching risk communication. With little effort doctors
      could taught the simple techniques of risk communication, which would make most
      of their statistical confusion disappear.

PMID- 23535553
TI  - [New genetic tests and their clinical utility for cancer screening].
AB  - The promises resulting from the decoding of the human genome have not been
      fulfilled to the extent as expected. At the same time it is fair to say that the
      results of recent genetic research have not been useless. In the area of familial
      cancer the clinical benefit of genetic testing for healthy family members is very
      convincing, where the risk of disease can be reduced substantially through
      preventive interventions. For example, prophylactic mastectomy and premenopausal
      ovariectomy can reduce the cancer risk in carriers of BRCA1 and BRCA2 mutations
      dramatically. In recent years, the research has moved towards the decoding of the
      genetic causes of sporadic cancers as well. Genome-wide and hypothesis-free
      association studies have linked different chromosome regions to cancer. By this,
      new insights into disease mechanisms could be gained, an important requirement
      for the development of diagnostics and drugs. However, what is missing is the
      evidence that the associated SNPs (Single Nucleotide Polymorphisms) could be
      useful for individual risk calculation or for stratification of the population
      into groups with different preventive or screening needs.

PMID- 23535554
TI  - Thermal and hemodynamic response to whole-body cryostimulation in healthy
      subjects.
AB  - Whole-body cryotherapy (WBC) is an increasing applied cryotherapeutic method,
      that involves application of a cryotherapeutic factor to stimulate the body by
      the means of intense hypothermia of virtually the body's entire area. This method
      is still not well recognized in Western Europe. However in recent years it is
      becoming increasingly popular in sports medicine and also in clinical
      application. Cryotherapeutic agents used in WBC are considered to be a strong
      stress stimulus which is associated with a variety of changes in functional
      parameters, particularly of the cardiovascular and autonomic nervous systems.
      However, such strong influence upon the entire body could be associated with the
      risk of unexpected reactions which might be dangerous for homeostasis. The
      present study evaluated the complex hemodynamic physiological reactions in
      response to WBC exposure in healthy subjects. Thirty healthy male volunteers
      participated. Each subject was exposed to WBC (-120 degrees C) for 3-min. None of
      the participants had been exposed to such conditions previously. The research was
      conducted with modern and reliable measurements techniques, which assessed
      complex hemodynamic reactions and skin temperature changes non-invasively. All
      measurements were performed four times (before WBC, after WBC, WBC+3h and WBC+6h)
      with a Task Force Monitor (TFM - CNSystems, Medizintechnik, Gratz, Austria). Body
      superficial temperature was measured by infrared thermographic techniques - infra
      red camera Flir P640 (Flir Systems Inc., Sweden). Our results show a significant
      decrease in heart rate, cardiac output, and increase in stroke volume, total
      peripheral resistance and baroreceptors reflex sensitivity. These changes were
      observed just after WBC exposure. At stages WBC+3h and WBC+6h there was observed
      a significant drop in baroreceptors reflex sensitivity due to increased
      thermogenesis. In conclusion, the present findings suggest that WBC strongly
      stimulates the baroreceptor cardiac reflex in response to body fluid changes
      which sequentially modulate HR and BP control in supine and resting healthy
      subjects. The study was performed on randomized and homogenic group of young
      healthy subjects. Our findings are important for WBC safety determination in
      research and clinical studies.

PMID- 23535555
TI  - YAG:Ce nanoparticle lightsources.
AB  - We investigate the luminescence properties of 10 nm yttrium aluminum garnet (YAG)
      nanoparticles doped with Ce ions at 0.2%, 4% and 13% that are designed as active
      probes for scanning near-field optical microscopy. They are produced by a
      physical method without any subsequent treatment, which is imposed by the desired
      application. The structural analysis reveals the amorphous nature of the
      particles, which we relate to some compositional defects as indicated by the
      elemental analysis. The optimum emission is obtained with a doping level of 4%.
      The emission of the YAG nanoparticles doped at 0.2% is strongly perturbed by the
      crystalline disorder whereas the 13% doped particles hardly exhibit any
      luminescence. In the latter case, the presence of Ce(4+) ions is confirmed,
      indicating that the Ce concentration is too high to be incorporated efficiently
      in YAG nanoparticles in the trivalent state. By a unique procedure combining
      cathodoluminescence and Rutherford backscattering spectrometry, we demonstrate
      that the enhancement of the particle luminescence yield is not proportional to
      the doping concentration, the emission enhancement being larger than the Ce
      concentration increase. Time-resolved photoluminescence reveals the presence of
      quenching centres likely related to the crystalline disorder as well as the
      presence of two distinct Ce ion populations. Eventually, nano-cathodoluminescence
      indicates that the emission and therefore the distribution of the doping Ce ions
      and of the defects are homogeneous.

PMID- 23535556
TI  - Smoking cessation, depression, and exercise: empirical evidence, clinical needs,
      and mechanisms.
AB  - INTRODUCTION: Smoking is significantly more common among persons with major
      depressive disorders (MDDs). Furthermore, smokers with MDD report more
      difficulties when they quit smoking (greater withdrawal symptoms, higher
      probability of relapse). The aim of this narrative review is to describe research
      on exercise and depression and exercise and smoking cessation. METHODS: We have
      critically reviewed various smoking cessation intervention programs for
      depressive smokers examining (a) the protective effect of exercise against
      relapse for smokers with MDD and (b) the benefits of exercise for treating
      withdrawal symptoms. We have also reviewed the current literature investigating
      the mechanisms between exercise-depression and exercise-smoking. RESULTS: This
      review suggests that exercise may reduce depressive symptoms following cessation
      and provide a useful strategy for managing withdrawal symptoms in smokers with
      MDD. Various psychological, biological, and genetic hypotheses have been tested
      (e.g., distraction hypothesis, expectations hypothesis, cortisol hypothesis) and
      few have obtained significant results. CONCLUSIONS: It might be beneficial for
      health professionals to recommend physical activity and promote supervised
      exercise sessions for smokers with MDD during smoking cessation. Future research
      needs to examine relationships between exercise, smoking, and depression with
      transdisciplinary and ecological momentary assessment.

PMID- 23535557
TI  - Trunk Recovery Scale: a new tool to measure posture control in patients with
      severe acquired brain injury. A study of the psychometric properties.
AB  - BACKGROUND: Posture control appears deeply impaired in patients with severe
      Acquired Brain Injury (ABI). One of the main goals of neurorehabilitation
      specialists is to try to assess this neural function in a standardized manner.
      However, the tests available to evaluate posture control recovery after brain
      damage were developed for patients with focal neurological signs. We therefore
      developed a new test, the Trunk Recovery Scale (TRS). AIM: To evaluate the inter
      rater reliability, internal consistency, external validity, and sensitivity of
      TRS in patients with ABI. DESIGN: Validation study. SETTING: We examined 59
      patients hospitalized after a brain injury in the Intensive and the Extensive
      Rehabilitation Units of our hospital. POPULATION: Patients with diagnosis of
      severe ABI with the capacity to respond to simple verbal orders and with a Level
      of Cognitive Functioning Scale (LCF scale) >= 4. METHODS: Three raters
      independently assessed 20 subjects. One of the raters also assessed 39 additional
      subjects using TRS, Trunk Control Test (TCT), and Functional Independence Measure
      (FIM), and repeated the evaluation after 30 days. RESULTS: The Inter-rater
      reliability was generally high (ICC=0,97 and 0,92 for total score and different
      subscales). Weighted Kappa values indicated "substantial agreement" except for
      items 2, 7, and 12. Internal consistency was good: Cronbach's coefficients were
      0.900 and 0.910 for different subscales, and the elimination of one item at a
      time did not substantially improve the internal consistency. External validity
      was excellent (Spearman rank correlations =0.943 and 0.849 for TCT and FIM).
      Sensitivity was good. CONCLUSIONS: Our data confirm that TRS reliably assesses
      posture control in patients with severe ABI. However, as the sample size of
      internal consistency and validity was limited, the results may be overestimated.
      We therefore propose that this study be considered the first in a series of
      similar studies. This series should include a Rasch Analysis, which would further
      evaluate the suitability of keeping or removing items with less consistency and
      would define the mathematical properties of different subscales and the total
      score. CLINICAL REHABILITATION IMPACT: Our data confirm that TRS detects subtle
      but potentially meaningful motor changes in patients and can therefore allow
      clinicians to document treatment effectiveness and define treatment objectives.

PMID- 23535558
TI  - High incidence of RAS signalling pathway mutations in MLL-rearranged acute
      myeloid leukemia.

PMID- 23535560
TI  - Covalent inhibition of SUMO and ubiquitin-specific cysteine proteases by an in
      situ thiol-alkyne addition.
AB  - Posttranslational modification of proteins with ubiquitin and ubiquitin-like
      modifiers such as SUMO can be reverted by specific proteases, also referred to as
      deubiquitinases and isopeptidases, most of which are cysteine-dependent. We have
      found that the replacement of the conserved C-terminal glycine with
      propargylamine converts SUMO and ubiquitin to highly efficient covalent
      inhibitors of their cognate cysteine proteases. Attack of the catalytic cysteine
      onto the terminal alkyne results in the formation of a vinyl sulfide linkage.
      Although this reaction is reminiscent of the inhibitory mechanism of the
      isosteric nitrile inhibitors it was unexpected due to the low electrophilicity of
      the alkyne group. We show that a precise location of the functional group in the
      active site of the protease is crucial for the reaction, which was not inhibited
      by the presence of a radical scavenger. Furthermore, a mutational study of key
      catalytic residues in the SUMO-protease Senp1, that is H533A and D550A of the
      catalytic triad and Q597A as part of the oxyanion hole, revealed that these
      residues are not required for the observed covalent adduct formation. We
      therefore propose that the reaction is an in situ thiol-alkyne addition. Due to
      the high chemical inertness of the alkyne moiety the respective protease
      inhibitors should be well-suited for cellular and therapeutic applications. In
      keeping with this idea, selective labeling with propargylated SUMO and Ub probes
      was observed in lysates of cell lines expressing the cognate proteases after
      transient transfection.

PMID- 23535559
TI  - SYK regulates mTOR signaling in AML.
AB  - Spleen tyrosine kinase (SYK) was recently identified as a new target in acute
      myeloid leukemia (AML); however, its mechanistic role in this disease is poorly
      understood. Based on the known interaction between SYK and mammalian target of
      rapamycin (mTOR) signaling in lymphoma, we hypothesized that SYK may regulate
      mTOR signaling in AML. Both small-molecule inhibition of SYK and SYK-directed
      shRNA suppressed mTOR and its downstream signaling effectors, as well as its
      upstream activator, AKT. Moreover, the inhibition of multiple nodes of the
      phosphatidylinositol 3'-kinase (PI3K) signaling pathway enhanced the effects of
      SYK suppression on AML cell viability and differentiation. Evaluation of the
      collateral mitogen-activated protein kinase (MAPK) pathway revealed a
      heterogeneous response to SYK inhibition in AML with downregulation of MEK and
      extracellular signal-regulated kinase (ERK) phosphorylation in some AML cell
      lines but a paradoxical increase in MEK/ERK phosphorylation in RAS-mutated AML.
      These studies reveal SYK as a regulator of mTOR and MAPK signaling in AML and
      demonstrate that inhibition of PI3K pathway activity enhances the effects of SYK
      inhibition on AML cell viability and differentiation. 

PMID- 23535561
TI  - CD4 mimics as HIV entry inhibitors: lead optimization studies of the aromatic
      substituents.
AB  - Several CD4 mimics have been reported as HIV-1 entry inhibitors that can
      intervene in the interaction between a viral envelope glycoprotein gp120 and a
      cell surface protein CD4. Our previous SAR studies led to a finding of a highly
      potent analogue 3 with bulky hydrophobic groups on a piperidine moiety. In the
      present study, the aromatic ring of 3 was modified systematically in an attempt
      to improve its antiviral activity and CD4 mimicry which induces the
      conformational changes in gp120 that can render the envelope more sensitive to
      neutralizing antibodies. Biological assays of the synthetic compounds revealed
      that the introduction of a fluorine group as a meta-substituent of the aromatic
      ring caused an increase of anti-HIV activity and an enhancement of a CD4 mimicry,
      and led to a novel compound 13a that showed twice as potent anti-HIV activity
      compared to 3 and a substantial increase in a CD4 mimicry even at lower
      concentrations.

PMID- 23535563
TI  - Investigation of the role of linker moieties in bifunctional tacrine hybrids.
AB  - Alzheimer's disease (AD) is a complex neurological disorder with multiple inter
      connected factors playing roles in the onset and progression of the disease. One
      strategy currently being explored for the development of new therapeutics for AD
      involves linking tacrine, a known acetylcholinesterase (AChE) inhibitor, to
      another drug to create bifunctional hybrids. The role and influence on activity
      of the linker moiety in these hybrids remains ill-defined. In this study, three
      series of 6-chlorotacrine with linkers varying in terminal functional group and
      length were synthesized, evaluated for AChE inhibition, and compared to tacrine
      and 6-chlorotacrine-mefenamic acid hybrids. Out of the compounds with terminal
      amine, methyl, and hydroxyl moieties tested, several highly potent molecules (low
      nanomolar IC50 values) comprised of linkers with terminal amines were identified.
      These 6-chlorotacrine with linkers were significantly more potent than tacrine
      alone and were often more potent than similar 6-chlorotacrine-mefenamic acid
      hybrids.

PMID- 23535562
TI  - One-pot multi-enzyme (OPME) chemoenzymatic synthesis of sialyl-Tn-MUC1 and sialyl
      T-MUC1 glycopeptides containing natural or non-natural sialic acid.
AB  - A series of STn-MUC1 and ST-MUC1 glycopeptides containing naturally occurring and
      non-natural sialic acids have been chemoenzymatically synthesized from Tn-MUC1
      glycopeptide using one-pot multienzyme (OPME) approaches. In situ generation of
      the sialyltransferase donor cytidine 5'-monophosphate-sialic acid (CMP-Sia) using
      a CMP-sialic acid synthetase in the presence of an extra amount of cytidine 5'
      triphosphate (CTP) and removal of CMP from the reaction mixture by flash C18
      cartridge purification allow the complete consumption of Tn-MUC1 glycopeptide for
      quantitative synthesis of STn-MUC1. A Campylobacter jejuni beta1-3GalT
      (CjCgtBDelta30-His6) mutant has been found to catalyze the transfer of one or
      more galactose residues to Tn-MUC1 for the synthesis of T-MUC1 and galactosylated
      T-MUC1. Sialylation of T-MUC1 using Pasteurella multocida alpha2-3
      sialyltransferase 3 (PmST3) with Neisseria meningitidis CMP-sialic acid
      synthetase (NmCSS) and Escherichia coli sialic acid aldolase in one pot produced
      ST-MUC1 efficiently. These glycopeptides are potential cancer vaccine candidates.

PMID- 23535564
TI  - Sol-gel synthesis of mesoporous mixed Fe2O3/TiO2 photocatalyst: application for
      degradation of 4-chlorophenol.
AB  - Photosensitization of TiO2 with other transition metal oxides can extend its
      light absorption property in the visible region. Such materials could emerge as
      excellent catalysts for solar photocatalytic degradation. In the present study
      mesoporous Fe2O3/TiO2 (10, 30, 50, 70 and 90 wt% Fe2O3) photocatalysts were
      synthesized by sol-gel process and characterized using different techniques. The
      XRD patterns exhibited the presence of mesoporous structure and isomorphic
      substitution of Fe(3+) in TiO2 at low Fe(3+) loading and Ti(4+) in Fe2O3 at high
      Fe(3+) loading. The XPS results revealed the presence of Ti(4+) and Fe(3+) in
      Fe2O3/TiO2 materials. The DRS UV-vis spectra showed a shift in the band gap
      excitation of TiO2 to longer wavelength, thus illustrating incorporation of
      Fe(3+) in TiO2. In addition, free TiO2 and Fe2O3 particles were also present.
      Their photocatalytic activity was tested for the degradation of 4-chlorophenol in
      aqueous medium using sunlight. The activity of the catalysts followed the order:
      meso-30 wt% Fe2O3/TiO2>meso-10 wt% Fe2O3/TiO2>meso-50 wt% Fe2O3/TiO2>meso-70
      Fe2O3/TiO2>meso-90 wt% Fe2O3/TiO2>meso-Fe2O3>meso-TiO2. This order concluded that
      mesoporous Fe2O3/TiO2 could be an active catalyst for pollutant degradation, as
      TiO2 with framework Fe(3+) and photosensitization with free Fe2O3 were involved
      in the activity.

PMID- 23535565
TI  - Antithrombotic activity of HY023016, a novel Dabigatran prodrug evaluated in
      animal thrombosis models.
AB  - INTRODUCTION: Thrombin is a multifunctional trypsin-like serine protease that
      plays key roles in coagulation and thrombogenesis. HY023016, a novel Dabigatran
      prodrug, is an oral direct thrombin inhibitor. The purpose of this study was to
      compare the anti-thrombotic activities and haemorrhagic effects of HY023016 with
      Dabigatran etexilate and tetramethylpyrazine in several animal thrombosis models.
      METHODS: To investigate drug exposure, liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method was used to determine the pharmacokinetic profile
      of HY023016. After single intragastric administrations of HY023016, Dabigatran
      etexilate or tetramethylpyrazine, the anti-thrombotic activities were evaluated
      through rabbit jugular vein thrombosis model, rat inferior vena cava thrombosis
      model, ex vivo rabbit platelet aggregation assay, in vivo rabbit coagulation
      assay, and direct thrombin binding assay. Meanwhile, we evaluated the effect of
      HY023016 on expression of tissue factor (TF) by RT-PCR. Rabbit cuticle bleeding
      assay and mouse tail bleeding assay were applied to evaluate the effects of
      HY023016 on haemorrhage. RESULTS: Pharmacokinetic parameters indicated that
      HY023016 can convert to Dabigatran and tetramethylpyrazine. Our studies showed
      that HY023016 was able to significantly inhibit thrombus formation in a dose
      dependent manner in rabbit and rat models (P<0.05). Similarly, it was able to
      dose-dependently inhibit thrombin- or ADP-induced platelet aggregation,
      prolonging the activated partial thromboplastin time (APTT) and prothrombin time
      (PT), inhibiting the activity of thrombin and inhibiting thrombin- or ADP-induced
      expression of TF (P<0.05 or 0.01). Dabigatran etexilate was also able to dose
      dependently and significantly inhibit thrombus formation (P<0.01) but was unable
      to affect ADP-induced platelet aggregation and expression of TF. In contrast,
      tetramethylpyrazine could only exhibit mild antithrombotic activity compared with
      HY023016 and Dabigatran etexilate (P<0.05). HY023016 could prolong bleeding time
      (P<0.001), but the prolongations were significantly less than Dabigatran
      etexilate (P<0.05). CONCLUSION: HY023016 showed thrombosis-inhibition activities
      comparable to those of Dabigatran etexilate, but better than those of
      tetramethylpyrazine. The attendant bleeding risk of HY023016 was lower than
      Dabigatran etexilate in rabbits and mice.

PMID- 23535566
TI  - A low-volume, single pass in-vitro system of high shear thrombosis in a stenosis.
AB  - INTRODUCTION: Arterial thrombosis leading to heart attack and stroke requires the
      rapid accumulation of millions of platelets under pathologically high shear.
      Previous in vitro systems studying platelets typically use endpoints that
      emphasize platelet-surface effects rather than large-scale platelet-platelet
      accumulation that precedes occlusion. Further, most platelet tests do not
      recreate shear rates present during arterial occlusion. We present an alternative
      flow system to study large thrombus formation under pathologic shear conditions
      in an anatomic stenosis with reasonable volumes of human blood. MATERIALS AND
      METHODS: An in-vitro system using a syringe pump was created to subject low
      volume (<30 mLs), whole blood samples to very high shear rates (>3,500 s(-1))
      through a stenosis. Thrombus was quantified using an optical microscope from
      initial deposition to large scale accumulation. Images were taken using a high
      definition camera in real time. RESULTS AND CONCLUSIONS: Occlusive thrombus
      blocks the collagen-coated lumen with millions of platelets using human whole,
      heparinized blood. Rapid Platelet Accumulation rates in human blood are 4.5+/-2.4
      MUm(3)/MUm(2)/min (n=21). There is an initial lag time of 7.4+/-3.8 min (n=21)
      before the onset of large scale thrombosis. The rates of platelet accumulation in
      vitro are consistent with the clinical timescale of coronary or carotid artery
      occlusion. Porcine blood has a faster accumulation rate of 9.6+/-6.1
      MUm(3)/MUm(2)/min (n=7, p<0.05) and a shorter lag time of 2.7+/-0.5 min (n=7,
      p<0.05). The long lag time for large thrombus formation suggests that some in
      vitro assays will miss the main mechanism creating thrombotic occlusion.

PMID- 23535567
TI  - Serum monomeric alpha2-macroglobulin as a clinical biomarker in diabetes.
AB  - OBJECTIVE: Despite the number of potential biomarker proteins for diabetes, very
      few of them have proven useful as clinically beneficial indicators, because of
      the technical difficulties associated with their identification among highly
      abundant serum proteins. We attempted to identify a protein with distinguishable
      expression in human diabetes. METHODS: We applied a highly efficient strategy for
      the purification of endogenous low abundance proteins from diabetic and non
      diabetic serum samples. Extracted sera were fractionated by SDS-PAGE and protein
      bands were isolated and analyzed by mass spectrometry using an ion-trap mass
      spectrometer. The identities of the proteins were confirmed by western blotting
      and the serum levels evaluated. RESULTS: A significantly upregulated protein in
      diabetic patients was identified as monomeric alpha2-macroglobulin. Its tetramer,
      another dominant circulating molecular form, was only marginally increased in
      diabetes. CONCLUSION: Serum monomeric alpha2-macroglobulin is highly expressed in
      many diabetic subjects. It is identical to the human 'cardiac isoform of alpha2
      macroglobulin' described in the literature, a well-known acute phase serum
      biomarker protein mechanistically involved in cardiac and atherosclerotic
      diseases.

PMID- 23535569
TI  - Subclinical optic neuritis in neuromyelitis optica.

PMID- 23535568
TI  - A repressor protein, Mnt, is a novel negative regulator of vascular smooth muscle
      cell hypertrophy by angiotensin II and neointimal hyperplasia by arterial injury.
AB  - OBJECTIVE: The Max-interacting protein Mnt is a transcriptional repressor that
      can antagonize the transcriptional and proliferation-related activities of Myc.
      Here, we tested the hypothesis that Mnt is a negative regulator of pathological
      vascular remodeling. METHODS: Adenovirus encoding Mnt or control GFP was infected
      to cultured rat vascular smooth muscle cells (VSMC) and carotid arteries after a
      balloon angioplasty. RESULTS: In VSMC, adenoviral gene transfer of Mnt suppressed
      angiotensin II-induced protein expression of early growth response protein-1
      (Egr1) and its promoter activation. Mnt adenovirus did not interfere with
      upstream signaling of angiotensin II. Angiotensin II-induced protein accumulation
      in VSMC was inhibited by Mnt adenovirus. Mnt adenovirus also inhibited platelet
      derived growth factor-induced VSMC proliferation. Moreover, Mnt adenovirus
      prevented neointima formation in response to arterial injury. The adenoviral Mnt
      gene transfer also prevented Egr1 induction in neointima. CONCLUSION: These data
      identify Mnt as a previously unrecognized negative regulator of pathological
      vascular remodeling.

PMID- 23535570
TI  - Toxocariasis of the optic disc.
AB  - A healthy 46-year-old man presented with decreased vision in the right eye after
      ingestion of raw meat. On funduscopic examination, a cystic lesion was found on
      an edematous right optic disc with adjacent serous retinal detachment. Optical
      coherence tomography confirmed a peripapillary serous retinal detachment and a
      well-demarcated cystic lesion (200 * 200 * 500 MUm) in the right eye. The patient
      had moderate eosinophilia and was seropositive for anti-Toxocara IgG antibody.
      Diagnosed with ocular toxocariasis, he was treated with systemic corticosteroids
      and albendazole with improvement in vision and fundus appearance.

PMID- 23535571
TI  - Bombyx mori nucleopolyhedrovirus BmP95 plays an essential role in budded virus
      production and nucleocapsid assembly.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) BmP95 is a highly conserved gene that is
      found in all of the baculovirus genomes sequenced to date and is also found in
      nudiviruses. To investigate the role of BmP95 in virus infection in vitro, a
      BmP95 deletion virus (vBmP95-De) was generated by homologous recombination in
      Escherichia coli. Fluorescence and light microscopy and titration analysis
      indicated that the BmP95 deletion bacmid led to a defect in production of
      infectious budded virus (BV). However, deletion of BmP95 did not affect viral DNA
      replication. Electron microscopy showed that masses of aberrant tubular
      structures were present in cells transfected with the BmP95 deletion bacmid,
      indicating that deletion of BmP95 affected assembly of the nucleocapsid. This
      defect could be rescued by insertion of full-length BmP95 into the polyhedrin
      locus of the BmP95-knockout bacmid but not the N-terminal domain of BmP95.
      Together, these results showed that full-length BmP95 is essential for BV
      production and is required for nucleocapsid assembly.

PMID- 23535572
TI  - Axin expression enhances herpes simplex virus type 1 replication by inhibiting
      virus-mediated cell death in L929 cells.
AB  - Herpes simplex virus type 1 (HSV-1) replicates in various cell types and induces
      early cell death, which limits viral replication in certain cell types. Axin is a
      scaffolding protein that regulates Wnt signalling and participates in various
      cellular events, including cellular proliferation and cell death. The effects of
      axin expression on HSV-1 infection were investigated based on our initial
      observation that Wnt3a treatment or axin knockdown reduced HSV-1 replication.
      L929 cells expressed the axin protein in a doxycycline-inducible manner (L-axin)
      and enhanced HSV-1 replication in comparison to control cells (L-EV). HSV-1
      infection induced cell death as early as 6 h after infection through the necrotic
      pathway and required de novo protein synthesis in L929 cells. Subsequent analysis
      of viral protein expression suggested that axin expression led to suppression of
      HSV-1-induced premature cell death, resulting in increased late gene expression.
      In analysis of axin deletion mutants, the regulators of the G-protein signalling
      (RGS) domain were involved in the axin-mediated enhancement of viral replication
      and reduction in cell death. These results suggest that viral replication
      enhancement might be mediated by the axin RGS domain.

PMID- 23535573
TI  - Selective B-cell expression of the MHV-68 latency-associated M2 protein regulates
      T-dependent antibody response and inhibits apoptosis upon viral infection.
AB  - To better understand the role of the M2 protein of the murine herpes virus strain
      68 (MHV-68) in vivo, B-lymphocyte-restricted, M2-transgenic mice were
      constructed. The transgenic mice contained normal B-cell subpopulations in bone
      marrow, lymph nodes and spleen. After immunization with sheep red blood cells,
      spleens from M2-transgenic mice had increased germinal centres. Transgenic mice
      responded to the T-cell-dependent antigen keyhole limpet haemocyanin (KLH) with
      higher levels of secondary IgM and IgG2a antibodies than WT mice. Normal and M2
      transgenic mice were infected with WT and M2 frame-shift mutant (M2FS) MHV-68
      viruses. The pathogenesis of M2-transgenic mice infected with the M2-deficient
      mutant virus did not revert to that observed upon infection of normal mice with
      WT virus. However, the higher reactivation levels late after M2-transgenic mice
      were infected with WT virus reflected the importance of M2 as a target for the
      immune response, and thus with an impact on the establishment of latency.
      Finally, there was markedly less apoptosis in B-cells from M2-transgenic mice
      infected with either WT or M2FS mutant than from similarly infected WT mice,
      consistent with the published inhibitory influence of M2 on apoptosis in vitro.
      Thus, M2 provides a strategy to increase the pool of germinal centre B-cells
      through inhibition of apoptosis in the infected cell.

PMID- 23535574
TI  - Activation of CCR2+ human proinflammatory monocytes by human herpesvirus-6B
      chemokine N-terminal peptide.
AB  - Human monocytes expressing CCR2 with CD14 and CD16 can mediate antigen
      presentation, and promote inflammation, brain infiltration and immunosenescence.
      Recently identified roles are in human immunodeficiency virus infection,
      tuberculosis and parasitic disease. Human herpesvirus 6B (HHV-6B) encodes a
      chemokine, U83B, which is monospecific for CCR2, and is distinct from the related
      HHV-6A U83A, which activates CCR1, CCR4, CCR5, CCR6 and CCR8 on immune effector
      cells and dendritic cells. These differences could alter leukocyte-subset
      recruitment for latent/lytic replication and associated neuroinflammatory
      pathology. Therefore, cellular interactions between U83A and U83B could help
      dictate potential tropism differences between these viruses. U83A specificity is
      maintained in the 38-residue N-terminal spliced-truncated form. Here, we sought
      to determine the basis for the chemokine receptor specificity differences and
      identify possible applications. To do this we first analysed variation in a
      natural host population in sub-Saharan Africa where both viruses are equally
      prevalent and compared these to global strains. Analyses of U83 N-terminal
      variation in 112 HHV-6A and HHV-6B infections identified 6/38 U83A or U83B
      specific residues. We also identified a unique single U83A-specific substitution
      in one U83B sequence, 'U83BA'. Next, the variation effects were tested by
      deriving N-terminal (NT) 17-mer peptides and assaying activation of ex vivo human
      leukocytes, the natural host and cellular target. Chemotaxis of CCR2+ leukocytes
      was potently induced by U83B-NT, but not U83BA-NT or U83A-NT. Analyses of the
      U83B-NT activated population identified migrated CCR2+, but not CCR5+,
      leukocytes. The U83BA-NT asparagine-lysine14 substitution disrupted activity,
      thus defining CCR2 specificity and acting as a main determinant for HHV-6A/B
      differences in cellular interactions. A flow-cytometry-based shape-change assay
      was designed, and used to provide further evidence that U83B-NT could activate
      CCR2+CD14+CD16+ monocytes. This defines a potential antiviral target for HHV-6A/B
      disease and novel peptide immunomodulator for proinflammatory monocytes.

PMID- 23535575
TI  - L74V increases the reverse transcriptase content of HIV-1 virions with non
      nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and
      K101E+G190S, which results in increased fitness.
AB  - The fitness of non-nucleoside reverse transcriptase inhibitor (NNRTI) drug
      resistant reverse transcriptase (RT) mutants of HIV-1 correlates with the amount
      of RT in the virions and the RNase H activity of the RT. We wanted to understand
      the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and
      the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S
      viruses. We measured the amount of RT in virions and the polymerization and RNase
      H activities of mutant RTs compared to wild-type, K103N and G190S. We found that
      L100I, K101E and L74V did not change the polymerization or RNase H activities of
      K103N or G190S RTs. However, L100I and K101E reduced the amount of RT in the
      virions and subsequent addition of L74V restored RT levels back to those of G190S
      or K103N alone. We conclude that fitness changes caused by L100I, K101E and L74V
      derive from their effects on RT content.

PMID- 23535576
TI  - Nucleo-olivary inhibition balances the interaction between the reactive and
      adaptive layers in motor control.
AB  - In the acquisition of adaptive motor reflexes to aversive stimuli, the cerebellar
      output fulfills a double purpose: it controls a motor response and it relays a
      sensory prediction. However, the question of how these two apparently
      incompatible goals might be achieved by the same cerebellar area remains open.
      Here we propose a solution where the inhibition of the Inferior Olive (IO) by the
      cerebellar Deep Nuclei (DN) translates the motor command signal into a sensory
      prediction allowing a single cerebellar area to simultaneously tackle both
      aspects of the problem: execution and prediction. We demonstrate that having a
      graded error signal, the gain of the Nucleo-Olivary Inhibition (NOI) balances the
      generation of the response between the cerebellar and the reflexive controllers
      or, in other words, between the adaptive and the reactive layers of behavior.
      Moreover, we show that the resulting system is fully autonomous and can either
      acquire or erase adaptive responses according to their utility. 

PMID- 23535577
TI  - Facilitated aortic valve replacement with complete sternotomy and minimal skin
      incision using endoscopy: a case of surgical report.
AB  - Although median sternotomy is the accepted approach to the heart for cardiac
      surgery, minimally invasive approaches including partial sternotomies have
      recently been developed. However, such strategies might lead to sternal
      overriding, instability, and fracture or division of the internal thoracic
      arteries. Furthermore, a full sternotomy would be required to address
      unpredictable intra- or postoperative complications. This article describes
      minimally invasive aortic valve replacement via full sternotomy and minimal skin
      incision using an endoscope. 

PMID- 23535578
TI  - Metachronous bilateral pulmonary metastases from cancer of the ampulla duodeni.
AB  - We present a 76-year-old man who underwent two lung resections for metastases
      originating from cancer of the Ampulla duodeni, 9 years-after
      pancreaticoduodenectomy with lymphadenectomy. Pancreaticoduodenectomy was
      performed in 2002; histological examination of the original tumor revealed a
      stage III tubular adenocarcinoma (pT3, N0, M0). Repetitive lung resection was
      performed in 2007 (left S8) and 2011 (right S1 and extirpation of a pericardial
      cyst). Although rarely performed, resection of bilateral pulmonary metastases
      from carcinoma of the papilla of Vater was done to improve the patient's chances
      for longterm survival. 

PMID- 23535579
TI  - Extensive resection and double-patch reconstruction for left atrial myxoma.
AB  - The efficacy and safety of surgical intervention for atrial myxoma are
      established, but the operative approach to tumor resection and atrial
      reconstruction are controversial. A biatrial approach is generally used for
      excision of atrial myxoma and has many advantages. In contrast, there are a few
      reports about the method of double-patch reconstruction, and the right and left
      atrium are individually reconstructed with the two patches. We found it to be
      effective in the case reported here. We suggest that this method can be applied
      to atrial myxoma in which extensive resection is necessary. 

PMID- 23535580
TI  - Rupture and bleeding secondary to renal infarction in a patient with an abdominal
      aortic aneurysm.
AB  - A 57-year-old man had been followed up for severe left ventricular dysfunction
      after acute myocardial infarction with a left ventricular thrombus. He had been
      treated with anticoagulant and antiplatelet therapy and was admitted to our
      hospital because of abdominal pain and shock. He had no prior episode of trauma.
      The electrocardiogram (ECG) showed no changes compared with the previous ECG.
      Enhanced abdominal computed tomography (CT) showed a retroperitoneal hematoma
      around an abdominal aortic aneurysm (AAA) and the right kidney. We suspected
      rupture of AAA or the right kidney, and we performed AAA replacement with a Y
      shaped graft and nephrectomy of the right kidney. Pathological examination
      revealed hemorrhagic infarction of the lower part of the right kidney, with
      hemorrhage and rupture at the center of the infarct. In our case, enhanced CT
      showed extravasation from the lower part of the right kidney. In addition,
      postoperative echocardiography showed that the left ventricular thrombus had
      disappeared. We report a case of rupture and bleeding secondary to renal
      infarction in a patient with an AAA. 

PMID- 23535581
TI  - Coronary artery bypass grafting following simultaneous treatment of abdominal
      aortic aneurysm and peripheral arterial disease.
AB  - Atherosclerosis might affect all arterial segments of the vascular system, thus
      peripheral arterial disease (PAD) accompanying coronary artery disease (CAD) is
      not uncommon. In addition to this coexistence, abdominal aortic aneurysm (AAA) is
      frequently associated with CAD. Although treatment strategies of CAD and PAD or
      CAD and AAA has been reported previously, treatment of these three pathologies
      has not been reported. The management of a therapeutic strategy is important for
      avoiding perioperative mortality and morbidity in CAD associated with AAA and
      PAD. We are reporting our simultaneous treatment strategy of three pathologies
      with endovascular AAA repair, stent implantation into the superficial femoral
      artery (SFA) and coronary artery bypass grafting (CABG). 

PMID- 23535582
TI  - Successful treatment of pump pocket infection after left ventricular assist
      device implantation by negative pressure wound therapy and omental transposition.
AB  - A 52-year-old man suffering from dilated cardiomyopathy underwent implantable
      left ventricular assist device (LVAD) insertion as a bridge to transplantation.
      He presented with evidence of LVAD-related mediastinitis and pump pocket
      infection 57 days after the LVAD implantation. The mediastinum was reopened and
      irrigated. A large amount of pus was observed around the outflow and inflow
      conduits and in the pump pocket. Negative pressure wound therapy (NPWT) was
      initiated. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from
      blood and mediastinal pus. Enterobacter cloacae was also isolated by mediastinal
      pus culture after the beginning of the NPWT. Three weeks after the start of the
      NPWT, the pus culture became negative, and omental transposition and sternal
      closure were performed. Intravenous antibiotics were administered until day 42,
      with the treatment subsequently switched to oral antibiotics. He was discharged
      from the hospital on day 57 and followed up at the outpatient clinic. Our
      findings suggest that NPWT followed by omental transposition be useful to treat
      mediastinitis or pump pocket infection after implantable LVAD insertion. 

PMID- 23535583
TI  - Investigating the malleability of RNA aptamers.
AB  - Aptamers are short, single-stranded nucleic acids with structures that frequently
      change upon ligand binding and are sensitive to the ionic environment. To achieve
      facile application of aptamers in controlling cellular activities, a better
      understanding is needed of aptamer ligand binding parameters, structures,
      intramolecular mobilities and how these structures adapt to different ionic
      environments with consequent effects on their ligand binding characteristics.
      Here we discuss the integration of biochemical analysis with NMR spectroscopy and
      computational modeling to explore the relation between ligand binding and
      structural malleability of some well-studied aptamers. Several methods for
      determining aptamer binding affinity and specificity are discussed, including
      isothermal titration calorimetry, steady state fluorescence of 2-aminopurine
      substituted aptamers, and dye displacement assays. Also considered are aspects of
      molecular dynamics simulations specific to aptamers including adding ions and
      simulating aptamer structure in the absence of ligand when NMR spectroscopy or X
      ray crystallography structures of the unoccupied aptamer are not available. We
      focus specifically on RNA aptamers that bind small molecule ligands as would be
      applied in sensors or integrated into riboswitches such as to measure the
      products of metabolic activity. 

PMID- 23535584
TI  - Patient experiences with full electronic access to health records and clinical
      notes through the My HealtheVet Personal Health Record Pilot: qualitative study.
AB  - BACKGROUND: Full sharing of the electronic health record with patients has been
      identified as an important opportunity to engage patients in their health and
      health care. The My HealtheVet Pilot, the initial personal health record of the
      US Department of Veterans Affairs, allowed patients and their delegates to view
      and download content in their electronic health record, including clinical notes,
      laboratory tests, and imaging reports. OBJECTIVE: A qualitative study with
      purposeful sampling sought to examine patients' views and experiences with
      reading their health records, including their clinical notes, online. METHODS:
      Five focus group sessions were conducted with patients and family members who
      enrolled in the My HealtheVet Pilot at the Portland Veterans Administration
      Medical Center, Oregon. A total of 30 patients enrolled in the My HealtheVet
      Pilot, and 6 family members who had accessed and viewed their electronic health
      records participated in the sessions. RESULTS: Four themes characterized patient
      experiences with reading the full complement of their health information.
      Patients felt that seeing their records positively affected communication with
      providers and the health system, enhanced knowledge of their health and improved
      self-care, and allowed for greater participation in the quality of their care
      such as follow-up of abnormal test results or decision-making on when to seek
      care. While some patients felt that seeing previously undisclosed information,
      derogatory language, or inconsistencies in their notes caused challenges, they
      overwhelmingly felt that having more, rather than less, of their health record
      information provided benefits. CONCLUSIONS: Patients and their delegates had
      predominantly positive experiences with health record transparency and the open
      sharing of notes and test results. Viewing their records appears to empower
      patients and enhance their contributions to care, calling into question common
      provider concerns about the effect of full record access on patient well-being.
      While shared records may or may not impact overall clinic workload, it is likely
      to change providers' work, necessitating new types of skills to communicate and
      partner with patients.

PMID- 23535585
TI  - C-reactive protein exacerbates renal ischemia-reperfusion injury.
AB  - Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury
      (AKI), occurring with hypotension and cardiovascular surgery and inevitably
      during kidney transplantation. Mortality from AKI is high due to incomplete
      knowledge of the pathogenesis of IRI and the lack of an effective therapy.
      Inflammation accompanies IRI and increases the blood level of C-reactive protein
      (CRP), a biomarker of worsened outcomes in AKI. To test if CRP is causal in AKI
      we subjected wild-type mice (WT) and human CRP transgenic mice (CRPtg) to
      bilateral renal IRI (both pedicles clamped for 30 min at 37 degrees C then
      reperfused for 24 h). Serum human CRP level was increased approximately sixfold
      after IRI in CRPtg (10.62 +/- 1.31 MUg/ml at baseline vs. 72.01 +/- 9.41 MUg/ml
      at 24 h) but was not elevated by sham surgery wherein kidneys were manipulated
      but not clamped. Compared with WT, serum creatinine, urine albumin, and
      histological evidence of kidney damage were increased after IRI in CRPtg mice. RT
      PCR analysis of mRNA isolated from whole kidneys of CRPtg and WT subjected to IRI
      revealed that in CRPtg kidneys 1) upregulation of markers of macrophage classical
      activation (M1 markers) was blunted, 2) downregulation of markers of macrophage
      alternative activation (M2 markers) was more robust, and 3) expression of the
      activating receptor FcgammaRI was increased. Our finding that CRP exacerbates IRI
      induced AKI, perhaps by shifting the balance of macrophage activation and
      FcgammaR expression towards a detrimental portfolio, might make CRP a promising
      therapeutic target for the treatment of AKI.

PMID- 23535586
TI  - Adiponectin attenuates angiotensin II-induced oxidative stress in renal tubular
      cells through AMPK and cAMP-Epac signal transduction pathways.
AB  - Obesity is a risk factor for chronic kidney disease (CKD) progression.
      Circulating levels of adiponectin, an adipokine, decrease with obesity and play a
      protective role in the cardiovascular system. We hypothesized that adiponectin
      might also protect the kidney. Because activation of the renin-angiotensin system
      (RAS) is a contributor to CKD progression, we tested our hypothesis by studying
      the interactions between adiponectin and angiotensin II (ANG II) in renal tubular
      cells. Primary human renal proximal tubule cells expressed both adiponectin
      receptor 1 and 2 (adipoR1 and R2). ANG II-induced NADPH oxidase activation and
      oxidative stress were attenuated by adiponectin and dependent on adipoR1.
      Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside
      (AICAR) mimicked, while inhibition of AMPK with compound C abrogated, the effect
      of adiponectin on ANG II-induced activation of NADPH oxidase. Similarly, the
      effect of adiponectin was recapitulated by the stable cAMP analogs 4
      chlorophenylthio (pCPT)-cAMP and dibutyryl (db)-cAMP and blocked by the adenylate
      cyclase inhibitor SQ22536. Adiponectin did not activate PKA in renal tubular
      cells, and the specific PKA inhibitor myristoylated PKI (14-22) amide failed to
      block the inhibitory effect of adiponectin on ANG II-induced NADPH oxidase
      activation. In contrast, the specific Epac activator 8-(4-chlorophenylthio)-2'-O
      methyl (8-CPT-2-O-Me)-cAMP blocked ANG II-induced activation of NADPH oxidase, an
      effect that was reversed by coincubation with the AMPK inhibitor compound C.
      Finally, adiponectin attenuated ANG II-induced NF-kappaB activation and
      fibronectin protein expression. These in vitro findings support the hypothesis
      that adiponectin may attenuate the deleterious effects of ANG II in the kidney
      and play a protective role in CKD.

PMID- 23535588
TI  - One-dimensional weak antilocalization in single-crystal Bi2Te3 nanowires.
AB  - Angle-dependent magnetoconductance was measured on an individual surface-curved
      Bi2Te3 single-crystal nanowire fabricated by electrochemical deposition, where
      the evolution of surface conduction with wire diameters was investigated. It was
      found that the magnetoconductance of these nanowires in low field regime can be
      well described by one-dimensional (1D) weak antilocalization (WAL) model, where
      the dephasing length of the electrons follows T(-1/3) dependence but insensitive
      to the wire diameter. Meanwhile, such a 1D surface WAL was found to be enhanced
      significantly with the decrease of the wire diameter.

PMID- 23535589
TI  - Do windows or natural views affect outcomes or costs among patients in ICUs?
AB  - OBJECTIVE: To determine whether potential exposure to natural light via windows
      or to more pleasing views through windows affects outcomes or costs among
      critically ill patients. DESIGN: Retrospective cohort study. SETTING: An academic
      hospital in Philadelphia, PA. PATIENTS: Six thousand one hundred thirty-eight
      patients admitted to a 24-bed medical ICU and 6,631 patients admitted to a 24-bed
      surgical ICU from July 1, 2006, to June 30, 2010. INTERVENTIONS: Assignment to
      medical ICU rooms with vs. without windows and to surgical ICU rooms with natural
      vs. industrial views based on bed availability. MEASUREMENTS AND MAIN RESULTS: In
      primary analyses adjusting for patient characteristics, medical ICU patients
      admitted to rooms with (n = 4,093) versus without (n = 2,243) windows did not
      differ in rates of ICU (p = 0.25) or in-hospital (p = 0.94) mortality, ICU
      readmissions (p = 0.37), or delirium (p = 0.56). Surgical ICU patients admitted
      to rooms with natural (n = 3,072) versus industrial (n = 3,588) views experienced
      slightly shorter ICU lengths of stay and slightly lower variable costs.
      Instrumental variable analyses based on initial bed assignment and exposure time
      did not show any differences in any outcomes in either the medical ICU or
      surgical ICU cohorts, and none of the differences noted in primary analyses
      remained statistically significant when adjusting for multiple comparisons. In a
      prespecified subgroup analysis among patients with ICU length of stay greater
      than 72 hours, MICU windows were associated with reduced ICU (p = 0.02) and
      hospital mortality (p = 0.04); these results did not meet criteria for
      significance after adjustment for multiple comparisons. CONCLUSIONS: ICU rooms
      with windows or natural views do not improve outcomes or reduce costs of in
      hospital care for general populations of medical and surgical ICU patients.
      Future work is needed to determine whether targeting light from windows directly
      toward patients influences outcomes and to explore these effects in patients at
      high risk for adverse outcomes.

PMID- 23535590
TI  - Structures of protein-protein complexes involved in electron transfer.
AB  - Electron transfer reactions are essential for life because they underpin
      oxidative phosphorylation and photosynthesis, processes leading to the generation
      of ATP, and are involved in many reactions of intermediary metabolism. Key to
      these roles is the formation of transient inter-protein electron transfer
      complexes. The structural basis for the control of specificity between partner
      proteins is lacking because these weak transient complexes have remained largely
      intractable for crystallographic studies. Inter-protein electron transfer
      processes are central to all of the key steps of denitrification, an alternative
      form of respiration in which bacteria reduce nitrate or nitrite to N2 through the
      gaseous intermediates nitric oxide (NO) and nitrous oxide (N2O) when oxygen
      concentrations are limiting. The one-electron reduction of nitrite to NO, a
      precursor to N2O, is performed by either a haem- or copper-containing nitrite
      reductase (CuNiR) where they receive an electron from redox partner proteins a
      cupredoxin or a c-type cytochrome. Here we report the structures of the newly
      characterized three-domain haem-c-Cu nitrite reductase from Ralstonia pickettii
      (RpNiR) at 1.01 A resolution and its M92A and P93A mutants. Very high resolution
      provides the first view of the atomic detail of the interface between the core
      trimeric cupredoxin structure of CuNiR and the tethered cytochrome c domain that
      allows the enzyme to function as an effective self-electron transfer system where
      the donor and acceptor proteins are fused together by genomic acquisition for
      functional advantage. Comparison of RpNiR with the binary complex of a CuNiR with
      a donor protein, AxNiR-cytc551 (ref. 6), and mutagenesis studies provide direct
      evidence for the importance of a hydrogen-bonded water at the interface in
      electron transfer. The structure also provides an explanation for the
      preferential binding of nitrite to the reduced copper ion at the active site in
      RpNiR, in contrast to other CuNiRs where reductive inactivation occurs,
      preventing substrate binding.

PMID- 23535591
TI  - Techniques: 3D imaging of crystal defects.

PMID- 23535593
TI  - Microbiology: intraterrestrial lifestyles.

PMID- 23535592
TI  - Aegilops tauschii draft genome sequence reveals a gene repertoire for wheat
      adaptation.
AB  - About 8,000 years ago in the Fertile Crescent, a spontaneous hybridization of the
      wild diploid grass Aegilops tauschii (2n = 14; DD) with the cultivated tetraploid
      wheat Triticum turgidum (2n = 4x = 28; AABB) resulted in hexaploid wheat (T.
      aestivum; 2n = 6x = 42; AABBDD). Wheat has since become a primary staple crop
      worldwide as a result of its enhanced adaptability to a wide range of climates
      and improved grain quality for the production of baker's flour. Here we describe
      sequencing the Ae. tauschii genome and obtaining a roughly 90-fold depth of short
      reads from libraries with various insert sizes, to gain a better understanding of
      this genetically complex plant. The assembled scaffolds represented 83.4% of the
      genome, of which 65.9% comprised transposable elements. We generated
      comprehensive RNA-Seq data and used it to identify 43,150 protein-coding genes,
      of which 30,697 (71.1%) were uniquely anchored to chromosomes with an integrated
      high-density genetic map. Whole-genome analysis revealed gene family expansion in
      Ae. tauschii of agronomically relevant gene families that were associated with
      disease resistance, abiotic stress tolerance and grain quality. This draft genome
      sequence provides insight into the environmental adaptation of bread wheat and
      can aid in defining the large and complicated genomes of wheat species.

PMID- 23535594
TI  - Three-dimensional imaging of dislocations in a nanoparticle at atomic resolution.
AB  - Dislocations and their interactions strongly influence many material properties,
      ranging from the strength of metals and alloys to the efficiency of light
      emitting diodes and laser diodes. Several experimental methods can be used to
      visualize dislocations. Transmission electron microscopy (TEM) has long been used
      to image dislocations in materials, and high-resolution electron microscopy can
      reveal dislocation core structures in high detail, particularly in annular dark
      field mode. A TEM image, however, represents a two-dimensional projection of a
      three-dimensional (3D) object (although stereo TEM provides limited information
      about 3D dislocations). X-ray topography can image dislocations in three
      dimensions, but with reduced resolution. Using weak-beam dark-field TEM and
      scanning TEM, electron tomography has been used to image 3D dislocations at a
      resolution of about five nanometres (refs 15, 16). Atom probe tomography can
      offer higher-resolution 3D characterization of dislocations, but requires needle
      shaped samples and can detect only about 60 per cent of the atoms in a sample.
      Here we report 3D imaging of dislocations in materials at atomic resolution by
      electron tomography. By applying 3D Fourier filtering together with equal-slope
      tomographic reconstruction, we observe nearly all the atoms in a multiply twinned
      platinum nanoparticle. We observed atomic steps at 3D twin boundaries and imaged
      the 3D core structure of edge and screw dislocations at atomic resolution. These
      dislocations and the atomic steps at the twin boundaries, which appear to be
      stress-relief mechanisms, are not visible in conventional two-dimensional
      projections. The ability to image 3D disordered structures such as dislocations
      at atomic resolution is expected to find applications in materials science,
      nanoscience, solid-state physics and chemistry.

PMID- 23535595
TI  - Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha.
AB  - Macrophages activated by the Gram-negative bacterial product lipopolysaccharide
      switch their core metabolism from oxidative phosphorylation to glycolysis. Here
      we show that inhibition of glycolysis with 2-deoxyglucose suppresses
      lipopolysaccharide-induced interleukin-1beta but not tumour-necrosis factor-alpha
      in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide
      activated macrophages shows upregulation of glycolytic and downregulation of
      mitochondrial genes, which correlates directly with the expression profiles of
      altered metabolites. Lipopolysaccharide strongly increases the levels of the
      tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis
      is the principal source of succinate, although the 'GABA (gamma-aminobutyric
      acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate
      stabilizes hypoxia-inducible factor-1alpha, an effect that is inhibited by 2
      deoxyglucose, with interleukin-1beta as an important target. Lipopolysaccharide
      also increases succinylation of several proteins. We therefore identify succinate
      as a metabolite in innate immune signalling, which enhances interleukin-1beta
      production during inflammation.

PMID- 23535596
TI  - Draft genome of the wheat A-genome progenitor Triticum urartu.
AB  - Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and
      consumed food crops in the world. However, the complex polyploid nature of its
      genome makes genetic and functional analyses extremely challenging. The A genome,
      as a basic genome of bread wheat and other polyploid wheats, for example, T.
      turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is
      central to wheat evolution, domestication and genetic improvement. The progenitor
      species of the A genome is the diploid wild einkorn wheat T. urartu, which
      resembles cultivated wheat more extensively than do Aegilops speltoides (the
      ancestor of the B genome) and Ae. tauschii (the donor of the D genome),
      especially in the morphology and development of spike and seed. Here we present
      the generation, assembly and analysis of a whole-genome shotgun draft sequence of
      the T. urartu genome. We identified protein-coding gene models, performed genome
      structure analyses and assessed its utility for analysing agronomically important
      genes and for developing molecular markers. Our T. urartu genome assembly
      provides a diploid reference for analysis of polyploid wheat genomes and is a
      valuable resource for the genetic improvement of wheat.

PMID- 23535597
TI  - Predominant archaea in marine sediments degrade detrital proteins.
AB  - Half of the microbial cells in the Earth's oceans are found in sediments. Many of
      these cells are members of the Archaea, single-celled prokaryotes in a domain of
      life separate from Bacteria and Eukaryota. However, most of these archaea lack
      cultured representatives, leaving their physiologies and placement on the tree of
      life uncertain. Here we show that the uncultured miscellaneous crenarchaeotal
      group (MCG) and marine benthic group-D (MBG-D) are among the most numerous
      archaea in the marine sub-sea floor. Single-cell genomic sequencing of one cell
      of MCG and three cells of MBG-D indicated that they form new branches basal to
      the archaeal phyla Thaumarchaeota and Aigarchaeota, for MCG, and the order
      Thermoplasmatales, for MBG-D. All four cells encoded extracellular protein
      degrading enzymes such as gingipain and clostripain that are known to be
      effective in environments chemically similar to marine sediments. Furthermore, we
      found these two types of peptidase to be abundant and active in marine sediments,
      indicating that uncultured archaea may have a previously undiscovered role in
      protein remineralization in anoxic marine sediments.

PMID- 23535598
TI  - Structural basis for the drug extrusion mechanism by a MATE multidrug
      transporter.
AB  - Multidrug and toxic compound extrusion (MATE) family transporters are conserved
      in the three primary domains of life (Archaea, Bacteria and Eukarya), and export
      xenobiotics using an electrochemical gradient of H(+) or Na(+) across the
      membrane. MATE transporters confer multidrug resistance to bacterial pathogens
      and cancer cells, thus causing critical reductions in the therapeutic efficacies
      of antibiotics and anti-cancer drugs, respectively. Therefore, the development of
      MATE inhibitors has long been awaited in the field of clinical medicine. Here we
      present the crystal structures of the H(+)-driven MATE transporter from
      Pyrococcus furiosus in two distinct apo-form conformations, and in complexes with
      a derivative of the antibacterial drug norfloxacin and three in vitro selected
      thioether-macrocyclic peptides, at 2.1-3.0 A resolutions. The structures,
      combined with functional analyses, show that the protonation of Asp 41 on the
      amino (N)-terminal lobe induces the bending of TM1, which in turn collapses the N
      lobe cavity, thereby extruding the substrate drug to the extracellular space.
      Moreover, the macrocyclic peptides bind the central cleft in distinct manners,
      which correlate with their inhibitory activities. The strongest inhibitory
      peptide that occupies the N-lobe cavity may pave the way towards the development
      of efficient inhibitors against MATE transporters.

PMID- 23535599
TI  - Proteolytic elimination of N-myristoyl modifications by the Shigella virulence
      factor IpaJ.
AB  - Protein N-myristoylation is a 14-carbon fatty-acid modification that is conserved
      across eukaryotic species and occurs on nearly 1% of the cellular proteome. The
      ability of the myristoyl group to facilitate dynamic protein-protein and protein
      membrane interactions (known as the myristoyl switch) makes it an essential
      feature of many signal transduction systems. Thus pathogenic strategies that
      facilitate protein demyristoylation would markedly alter the signalling landscape
      of infected host cells. Here we describe an irreversible mechanism of protein
      demyristoylation catalysed by invasion plasmid antigen J (IpaJ), a previously
      uncharacterized Shigella flexneri type III effector protein with cysteine
      protease activity. A yeast genetic screen for IpaJ substrates identified ADP
      ribosylation factor (ARF)1p and ARF2p, small molecular mass GTPases that regulate
      cargo transport through the Golgi apparatus. Mass spectrometry showed that IpaJ
      cleaved the peptide bond between N-myristoylated glycine-2 and asparagine-3 of
      human ARF1, thereby providing a new mechanism for host secretory inhibition by a
      bacterial pathogen. We further demonstrate that IpaJ cleaves an array of N
      myristoylated proteins involved in cellular growth, signal transduction,
      autophagasome maturation and organelle function. Taken together, these findings
      show a previously unrecognized pathogenic mechanism for the site-specific
      elimination of N-myristoyl protein modification.

PMID- 23535600
TI  - A solution to release twisted DNA during chromosome replication by coupled DNA
      polymerases.
AB  - Chromosomal replication machines contain coupled DNA polymerases that
      simultaneously replicate the leading and lagging strands. However, coupled
      replication presents a largely unrecognized topological problem. Because DNA
      polymerase must travel a helical path during synthesis, the physical connection
      between leading- and lagging-strand polymerases causes the daughter strands to
      entwine, or produces extensive build-up of negative supercoils in the newly
      synthesized DNA. How DNA polymerases maintain their connection during coupled
      replication despite these topological challenges is unknown. Here we examine the
      dynamics of the Escherichia coli replisome, using ensemble and single-molecule
      methods, and show that the replisome may solve the topological problem
      independent of topoisomerases. We find that the lagging-strand polymerase
      frequently releases from an Okazaki fragment before completion, leaving single
      strand gaps behind. Dissociation of the polymerase does not result in loss from
      the replisome because of its contact with the leading-strand polymerase. This
      behaviour, referred to as 'signal release', had been thought to require a
      protein, possibly primase, to pry polymerase from incompletely extended DNA
      fragments. However, we observe that signal release is independent of primase and
      does not seem to require a protein trigger at all. Instead, the lagging-strand
      polymerase is simply less processive in the context of a replisome.
      Interestingly, when the lagging-strand polymerase is supplied with primed DNA in
      trans, uncoupling it from the fork, high processivity is restored. Hence, we
      propose that coupled polymerases introduce topological changes, possibly by
      accumulation of superhelical tension in the newly synthesized DNA, that cause
      lower processivity and transient lagging-strand polymerase dissociation from DNA.

PMID- 23535601
TI  - Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic
      pathway.
AB  - Cancer cells have metabolic dependencies that distinguish them from their normal
      counterparts. Among these dependencies is an increased use of the amino acid
      glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent
      tumours and the mechanisms whereby glutamine supports cancer metabolism remain
      areas of active investigation. Here we report the identification of a non
      canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma
      (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate
      dehydrogenase (GLUD1) to convert glutamine-derived glutamate into alpha
      ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC
      relies on a distinct pathway in which glutamine-derived aspartate is transported
      into the cytoplasm where it can be converted into oxaloacetate by aspartate
      transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and
      then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can
      potentially maintain the cellular redox state. Importantly, PDAC cells are
      strongly dependent on this series of reactions, as glutamine deprivation or
      genetic inhibition of any enzyme in this pathway leads to an increase in reactive
      oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any
      component enzyme in this series of reactions also results in a pronounced
      suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that
      the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the
      signature genetic alteration in PDAC, through the transcriptional upregulation
      and repression of key metabolic enzymes in this pathway. The essentiality of this
      pathway in PDAC and the fact that it is dispensable in normal cells may provide
      novel therapeutic approaches to treat these refractory tumours.

PMID- 23535605
TI  - Up-regulation of the canonical Wnt-3A and Sonic hedgehog signaling underlies
      melanocortin-induced neurogenesis after cerebral ischemia.
AB  - In experimental cerebral ischemia, melanocortin MC4 receptor agonists induce
      neuroprotection and neurogenesis with subsequent long-lasting functional
      recovery. Here we investigated the molecular mechanisms underlying melanocortin
      induced neurogenesis. Gerbils were subjected to transient global cerebral
      ischemia, then they were treated every 12 h, and until sacrifice, with 5-bromo-2'
      deoxyuridine (BrdU; to label proliferating cells), and the melanocortin analog
      [Nle(4),d-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) or saline.
      NDP-alpha-MSH increased hippocampus dentate gyrus (DG) expression of Wnt-3A, beta
      catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin
      (DCX), as detected at days 3, 6 and 10 after the ischemic insult. Further, an
      elevated number of BrdU immunoreactive cells was found at days 3 and 10, and an
      improved histological picture with reduced neuronal loss at day 10, associated
      with learning and memory recovery. Pharmacological blockade of the Wnt-3A/beta
      catenin and Shh pathways, as well as of melanocortin MC4 receptors, prevented all
      effects of NDP-alpha-MSH. These data indicate that, in experimental brain
      ischemia, treatment with melanocortins acting at MC4 receptors induces neural
      stem/progenitor cell proliferation in the DG by promptly and effectively
      triggering the canonical Wnt-3A/beta-catenin and Shh signaling pathways.
      Activation of these pathways is associated with up-regulation of the repair
      factor Zif268 and the neurogenesis facilitating factor IL-10, and it seems to
      address mainly toward a neuronal fate, as indicated by the increase in DCX
      positive cells.

PMID- 23535606
TI  - Activation of the cholinergic anti-inflammatory pathway by nicotine attenuates
      hepatic ischemia/reperfusion injury via heme oxygenase-1 induction.
AB  - Hepatic ischemia/reperfusion (I/R) elicits an excessive inflammatory response,
      posing a lethal threat to the host. Local inflammation may be regulated by the
      vagus nerve and activation of the nicotinic acetylcholine receptors may also
      suppress peripheral inflammation. We have previously demonstrated that heme
      oxygenase-1 (HO-1) protects the liver against I/R injury by modulating
      proinflammatory mediators. Here, we investigate the cytoprotective mechanisms of
      nicotine, a nicotinic acetylcholine receptor agonist, against liver injury caused
      by I/R. Mice were subjected to 60 min of ischemia followed by 3h of reperfusion.
      Nicotine (0.1, 0.3 and 1 mg/kg) and vehicle (saline) were administered
      intraperitoneally 20 min prior to ischemia. Serum alanine aminotransferase
      activity and lipid peroxidation levels increased after reperfusion, while total
      glutathione content decreased. These changes were markedly attenuated by
      nicotine. The levels of HO activity and HO-1 protein expression increased after
      reperfusion, and nicotine markedly augmented these increases. Serum levels of
      high mobility group box 1 and tumor necrosis factor-alpha increased after
      reperfusion, and nicotine prevented these increases. The nuclear translocation of
      NF-E2-related factor 2 and phosphorylation of both phosphatidyl inositol 3-kinase
      and Akt increased; nicotine also augmented these increases. The protein
      expression of nuclear factor-kappaB increased and nicotine attenuated this
      increase. Methyllycaconitine, a selective alpha7 nicotinic acetylcholine receptor
      antagonist, abolished these effects of nicotine. Furthermore, zinc
      protoporphyrin, an HO-1 inhibitor, also reversed the observed effects of
      nicotine. Our findings suggest that activation of alpha7 nicotinic acetylcholine
      receptor by nicotine ameliorates I/R-induced liver injury, and that this
      protection is likely due to inhibition of the inflammatory response through HO-1
      induction.

PMID- 23535607
TI  - Torsional resonance mode magnetic force microscopy: enabling higher lateral
      resolution magnetic imaging without topography-related effects.
AB  - We present experimental work that reveals the benefits of performing magnetic
      force microscopy measurements employing the torsional resonance mode of
      cantilever oscillation. This approach provides two clear advantages: the ability
      of performing magnetic imaging without topography-related interference and the
      significant lateral resolution improvement (approximately 15%). We believe that
      this work demonstrates a significant improvement to a versatile magnetic imaging
      technique widely used in academia and in industry.

PMID- 23535608
TI  - Continuous versus intermittent data collection of health care utilization.
AB  - BACKGROUND: In economic evaluations, participants have to report their health
      care utilization continuously during follow-up. To unburden participants,
      researchers often collect data intermittently (i.e., in at least 3 months a
      year). However, comparability of intermittent v. continuous data collection is
      unknown. Therefore, this study aimed to compare costs estimated with intermittent
      data collection of health care utilization with those based on continuous data
      collection. METHODS: We used continuous health care utilization data from a trial
      with 12 months of follow-up and simulated several intermittent data collection
      patterns. Then 3 imputation techniques--individual mean (IM), last observation
      carried forward (LOCF) and next observation carried backward (NOCB)--were used to
      estimate total annual costs. Estimated annual costs were compared with observed
      annual costs from continuous data collection both in the original sample and in
      1000 bootstrap samples. RESULTS: Analyses showed that intermittent data
      collection using cost diaries may offer good estimates of the actual total annual
      health expenditures. However, estimations of groups of costs differ between data
      collection patterns and imputation methods. The best estimations of annual total
      costs and groups of costs were obtained by random cohort data collection, using 3
      random cohorts, ensuring that at least a third of the participants were measuring
      costs each month, combined with IM imputation. Intermittent data collection of
      health expenditures carries a small risk of missing infrequent expensive events.
      CONCLUSIONS: Continuous cost data collection remains the first choice. However,
      if intermittent measurement is chosen, we recommend calculating annual costs from
      intermittent data collection in random cohorts, combined with IM imputation.

PMID- 23535610
TI  - Photocathodic behavior of ferroelectric Pb(Zr,Ti)O(3) films decorated with silver
      nanoparticles.
AB  - ITO/Pb(Zr,Ti)O(3) contacts and Ag nanoparticles were used to construct a novel
      ferroelectric film photocathode exhibiting a stable short-circuit photocurrent of
      110 MUA cm(-2) and an open-circuit voltage of 0.76 V under 100 mW cm(-2) Xe-lamp
      illumination and zero-bias versus SCE.

PMID- 23535609
TI  - Prenatal lipid-based nutrient supplements increase cord leptin concentration in
      pregnant women from rural Burkina Faso.
AB  - In developing countries, prenatal lipid-based nutrient supplements (LNSs) were
      shown to increase birth size; however, the mechanism of this effect remains
      unknown. Cord blood hormone concentrations are strongly associated with birth
      size. Therefore, we hypothesize that LNSs increase birth size through a change in
      the endocrine regulation of fetal development. We compared the effect of daily
      prenatal LNSs with multiple micronutrient tablets on cord blood hormone
      concentrations using a randomized, controlled design including 197 pregnant women
      from rural Burkina Faso. Insulin-like growth factors (IGF) I and II, their
      binding proteins IGFBP-1 and IGFBP-3, leptin, cortisol, and insulin were
      quantified in cord sera using immunoassays. LNS was associated with higher cord
      blood leptin mainly in primigravidae (+57%; P = 0.02) and women from the highest
      tertile of BMI at study inclusion (+41%; P = 0.02). We did not find any
      significant LNS effects on other measured cord hormones. The observed increase in
      cord leptin was associated with a significantly higher birth weight. Cord sera
      from small-for-gestational age newborns had lower median IGF-I (-9 MUg/L; P =
      0.003), IGF-II (-79 MUg/L; P = 0.003), IGFBP-3 (-0.7 MUg/L; P = 0.007), and
      leptin (-1.0 MUg/L; P = 0.016) concentrations but higher median cortisol (+18
      MUg/L; P = 0.037) concentrations compared with normally grown newborns. Prenatal
      LNS resulted in increased cord leptin concentrations in primigravidae and mothers
      with higher BMI at study inclusion. The elevated leptin concentrations could
      point toward a higher neonatal fat mass.

PMID- 23535611
TI  - Increased costs of cooperation help cooperators in the long run.
AB  - It has long been proposed that cooperation should increase in harsh environments,
      but this claim still lacks theoretical underpinnings. We modeled a scenario in
      which benefiting from altruistic behavior was essential to survival and
      reproduction. We used a spatial agent-based model to represent mutual cooperation
      enforced by environmental adversity. We studied two factors, the cost of
      unreciprocated cooperation and the environmental cost of living, which highlight
      a conflict between the short- and long-term rewards of cooperation. In the long
      run, cooperation is favored because only groups with a sufficient number of
      cooperators will survive. In the short run, however, harsh environmental costs
      increase the advantage of defectors in cooperator-defector interactions because
      the loss of resources leads to death. Our analysis sheds new light on the
      evolution of cooperation via interdependence and illustrates how selfish groups
      can incur short-term benefits at the cost of their eventual demise. We
      demonstrate how harsh environments select for cooperative phenotypes and suggest
      an explanation for the adoption of cooperative breeding strategies in human
      evolution. We also highlight the importance of variable population size and the
      role of socio-spatial organization in harsh environments.

PMID- 23535612
TI  - Spatial scaling of functional structure in bird and mammal assemblages.
AB  - Differences in trait composition, or functional structure, of assemblages across
      spatial scales may stem from the ability to tolerate local conditions
      (environmental filters) and from assembly rules (biological filters). However,
      disentangling their respective roles has proven difficult, and limited
      generalities have emerged from research on the spatial scaling of functional
      structure. Here we quantify differences in trait composition among 679 spatially
      nested (i.e., paired regional pool and local community) bird and mammal
      assemblages worldwide. Among the regional pool, we identify species with trait
      combinations within the range observed locally as the ecological species pool.
      The ecological species pool has a trait structure that is generally different
      from that of the regional pool, consistent with the operation of environmental
      filters. In contrast, local species trait structure generally shows little
      difference from that of the ecological pool. We find notable deviations from
      expectations based on equiprobable draws from the ecological pool. However, these
      deviations vary little across scales and broad environmental gradients. For
      mammals, but not birds, this is consistent with assembly rules. Thus, by
      conceptualizing ecological pools, we demonstrate that functional structure is
      jointly determined by processes causing both low and high functional differences
      between scales and are able to quantify their relative importance.

PMID- 23535613
TI  - Metapopulation dynamics of species with cryptic life stages.
AB  - Quantifying metapopulation dynamics is a challenging task. Difficulties
      particularly arise in species that possess unobservable resistance forms that
      bias the estimation of colonization and persistence rates. Here, we develop a
      general multistate occupancy model that allows estimation of species persistence
      for both normal and resistant forms, even when the latter are not detectable. We
      apply this model to an 11-year data set on the tropical freshwater snail
      Drepanotrema depressissimum in a network of 229 ponds. These ponds frequently dry
      out, and the snails can persist by aestivating in the ground, where they are not
      detected. Our model adequately captures this feature because it infers a high
      persistence rate for the resistant form, while models ignoring aestivation tend
      to overestimate extinction and colonization. In addition, we find that,
      surprisingly, colonization and persistence are even higher in sites prone to
      desiccation and during years with low rainfall than in more humid sites and
      years, suggesting that D. depressissimum favors unstable sites where competitors
      are rare and where it can rely on aestivation to persist. Our model has the
      potential to provide valuable insights into the metapopulation dynamics of many
      species that otherwise could hardly be studied because of the existence of
      undetectable life forms.

PMID- 23535614
TI  - The size-life span trade-off decomposed: why large dogs die young.
AB  - Large body size is one of the best predictors of long life span across species of
      mammals. In marked contrast, there is considerable evidence that, within species,
      larger individuals are actually shorter lived. This apparent cost of larger size
      is especially evident in the domestic dog, where artificial selection has led to
      breeds that vary in body size by almost two orders of magnitude and in average
      life expectancy by a factor of two. Survival costs of large size might be paid at
      different stages of the life cycle: a higher early mortality, an early onset of
      senescence, an elevated baseline mortality, or an increased rate of aging. After
      fitting different mortality hazard models to death data from 74 breeds of dogs,
      we describe the relationship between size and several mortality components. We
      did not find a clear correlation between body size and the onset of senescence.
      The baseline hazard is slightly higher in large dogs, but the driving force
      behind the trade-off between size and life span is apparently a strong positive
      relationship between size and aging rate. We conclude that large dogs die young
      mainly because they age quickly.

PMID- 23535615
TI  - Predicting population dynamics from the properties of individuals: a cross-level
      test of dynamic energy budget theory.
AB  - Individual-based models (IBMs) are increasingly used to link the dynamics of
      individuals to higher levels of biological organization. Still, many IBMs are
      data hungry, species specific, and time-consuming to develop and analyze. Many of
      these issues would be resolved by using general theories of individual dynamics
      as the basis for IBMs. While such theories have frequently been examined at the
      individual level, few cross-level tests exist that also try to predict population
      dynamics. Here we performed a cross-level test of dynamic energy budget (DEB)
      theory by parameterizing an individual-based model using individual-level data of
      the water flea, Daphnia magna, and comparing the emerging population dynamics to
      independent data from population experiments. We found that DEB theory
      successfully predicted population growth rates and peak densities but failed to
      capture the decline phase. Further assumptions on food-dependent mortality of
      juveniles were needed to capture the population dynamics after the initial
      population peak. The resulting model then predicted, without further calibration,
      characteristic switches between small- and large-amplitude cycles, which have
      been observed for Daphnia. We conclude that cross-level tests help detect gaps in
      current individual-level theories and ultimately will lead to theory development
      and the establishment of a generic basis for individual-based models and ecology.

PMID- 23535616
TI  - Migration tendency delays distributional response to differential survival
      prospects along a flyway.
AB  - When populations grow or decline, habitat selection may change due to local
      density-dependent processes, such as site dependence and interference. In
      seasonally migrating animals, nonbreeding distributions may be determined through
      these mechanisms of density dependence, which we examine here at a hemispheric
      scale for a long-distance migrating bird. Using summer and winter resightings of
      2,095 Eurasian spoonbills Platalea leucorodia leucorodia that were ringed in the
      Netherlands during 16 years of fast population growth, we show that neither site
      dependence nor interference fully explains their patterns of survival and winter
      distribution. Within their three main wintering areas, annual survival decreased
      with an increase in population size. While survival was consistently higher in
      the two European wintering areas (France, Iberia), most spoonbills migrated
      onward to winter in west Africa. The number of birds wintering in Europe
      increased, but not enough to maximize annual survival. We conclude that a
      constraint of tradition (their "migration tendency") inhibits birds from changing
      their migratory habits. We pose that this phenomenon may similarly constrain
      other migratory populations from rapidly responding to large-scale climate-
      and/or human-driven habitat changes at their wintering grounds.

PMID- 23535617
TI  - The effects of selective history and environmental heterogeneity on inbreeding
      depression in experimental populations of Drosophila melanogaster.
AB  - Inbreeding depression varies considerably among populations, but only some
      aspects of this variation have been thoroughly studied. Because inbreeding
      depression requires genetic variation, factors that influence the amount of
      standing variation can affect the magnitude of inbreeding depression.
      Environmental heterogeneity has long been considered an important contributor to
      the maintenance of genetic variation, but its effects on inbreeding depression
      have been largely ignored by empiricists. Here we compare inbreeding depression,
      measured in two environments, for 20 experimental populations of Drosophila
      melanogaster that have been maintained under four different selection regimes,
      including two types of environmentally homogeneous selection and two types
      environmentally heterogeneous selection. In line with theory, we find
      considerably higher inbreeding depression in populations from heterogeneous
      selection regimes. We also use our data set to test whether inbreeding depression
      is correlated with either stress or the phenotypic coefficient of variation (CV),
      as suggested by some recent studies. Though both of these factors are significant
      predictors of inbreeding depression in our study, there is an effect of assay
      environment on inbreeding depression that cannot be explained by either stress or
      CV.

PMID- 23535618
TI  - Multiple-strain infections of Borrelia afzelii: a role for within-host
      interactions in the maintenance of antigenic diversity?
AB  - Genetically diverse infections are common but little is known about what effects
      coinfecting strains have on each other in natural host-parasite systems. To
      explore the nature and consequences of interactions in the wild, we studied the
      tick-transmitted bacterium Borrelia afzelii in one of its main reservoir hosts,
      the bank vole Myodes glareolus. We measured overall infection intensity with
      quantitative polymerase chain reaction (PCR) and resolved the composition of
      multiple infections using strain-specific PCR assays targeting the ospC gene
      (which encodes an immunodominant surface protein). We found seven different
      strains, as defined by ospC genotype. There was little evidence for interactions
      affecting infection intensities, but strains were highly aggregated (i.e., there
      were more multiple infections than expected from random co-occurrence). Moreover,
      there was a positive correlation between the difference at the amino acid level
      between two OspC types and their degree of association. Overall, the observed
      patterns suggest that facilitation is more important than competition in this
      system and that more diverse infections have an advantage in establishing and/or
      maintaining infection. We propose that this advantage is one of the factors that
      favors antigenic diversity.

PMID- 23535619
TI  - Beating the odds in the aerial lottery: passive dispersers select conditions at
      takeoff that maximize their expected fitness on landing.
AB  - Passive airborne dispersal, in which the direction and distance of travel are
      determined by air movement, affects propagules and pollens, as well as mites,
      spiders, and small insect larvae. The takeoff or launch phase is, however,
      largely controlled, and many organisms become airborne only under particular
      weather conditions at takeoff, when the distribution of distances traveled will
      have a -3/2 power-law tail, a hallmark of Levy flights. Here these movement
      patterns are shown to maximize the likelihood of dispersing to the nearest
      unoccupied site, thereby maximizing expected fitness on landing.

PMID- 23535620
TI  - Fungal symbionts as manipulators of plant reproductive biology.
AB  - Symbioses have shaped the evolution of life, most notably through the fixation of
      heritable symbionts into organelles. The inheritance of symbionts promotes
      mutualism and fixation by coupling partner fitness. However, conflicts arise if
      symbionts are transmitted through only one sex and can shift host resources
      toward the sex through which they propagate. Such reproductive manipulators have
      been documented in animals with separate sexes but not in other phyla or sexual
      systems. Here we investigated whether the investment in male relative to female
      reproduction differed between hermaphroditic host plants with versus without a
      maternally inherited fungal symbiont. Plants with the fungus produced more seeds
      and less pollen than plants lacking the fungus, resulting in an ~40% shift in
      functional gender and a switch from male-biased to female-biased sex allocation.
      Given the ubiquity of endophytes in plants, reproductive manipulators of
      hermaphrodites may be widespread in nature.

PMID- 23535621
TI  - Dynamic disease management in Trachymyrmex fungus-growing ants (Attini:
      Formicidae).
AB  - Multipartner mutualisms have potentially complex dynamics, with compensatory
      responses when one partner is lost or relegated to a minor role. Fungus-growing
      ants (Attini) are mutualistic associates of basidiomycete fungi and antibiotic
      producing actinomycete bacteria; the former are attacked by specialized fungi
      (Escovopsis) and diverse generalist microbes. Ants deploy biochemical defenses
      from bacteria and metapleural glands (MGs) and express different behaviors to
      control contaminants. We studied four Trachymyrmex species that differed in
      relative abundance of actinomycetes to understand interactions among
      antimicrobial tactics that are contingent on the nature of infection. MG grooming
      rate and actinomycete abundance were negatively correlated. The two species with
      high MG grooming rates or abundant actinomycetes made relatively little use of
      behavioral defenses. Conversely, the two species with relatively modest
      biochemical defenses relied heavily on behavior. Trade-offs suggest that related
      species can evolutionarily diverge to rely on different defense mechanisms
      against the same threat. Neither bacterial symbionts nor MG secretions thus
      appear to be essential for mounting defenses against the specialized pathogen
      Escovopsis, but reduced investment in one of these defense modes tends to
      increase investment in the other.

PMID- 23535623
TI  - Fitting ecological process models to spatial patterns using scalewise variances
      and moment equations.
AB  - Ecological spatial patterns are structured by a multiplicity of processes acting
      over a wide range of scales. We propose a new method, based on the scalewise
      variance--that is, the variance as a function of spatial scale, calculated here
      with wavelet kernel functions--to disentangle the signature of processes that act
      at different and similar scales on observed spatial patterns. We derive exact and
      approximate analytical solutions for the expected scalewise variance under
      different individual-based, spatially explicit models for sessile organisms
      (e.g., plants), using moment equations. We further determine the probability
      distribution of independently observed scalewise variances for a given
      expectation, including complete spatial randomness. Thus, we provide a new
      analytical test of the null model of spatial randomness to understand at which
      scales, if any, the variance departs significantly from randomness. We also
      derive the likelihood function that is needed to estimate parameters of spatial
      models and their uncertainties from observed patterns. The methods are
      demonstrated through numerical examples and case studies of four tropical tree
      species on Barro Colorado Island, Panama. The methods developed here constitute
      powerful new tools for investigating effects of ecological processes on spatial
      point patterns and for statistical inference of process models from spatial
      patterns.

PMID- 23535624
TI  - Opposing mechanisms drive richness patterns of core and transient bird species.
AB  - Studies of biodiversity typically assume that all species are equivalent.
      However, some species in a community maintain viable populations in the study
      area, while others occur only occasionally as transient individuals. Here we show
      that North American bird communities can reliably be divided into core and
      transient species groups and that the richness of each group is driven by
      different processes. The richness of core species is influenced primarily by
      local environmental conditions, while the richness of transient species is
      influenced primarily by the heterogeneity of the surrounding landscape. This
      demonstrates that the well-known effects of the local environment and landscape
      heterogeneity on overall species richness are the result of two sets of processes
      operating differentially on core and transient species. Models of species
      richness should focus on explaining two distinct patterns, those of core and
      transient species, rather than a single pattern for the community as a whole.

PMID- 23535625
TI  - Revising the tolerance-fecundity trade-off; or, on the consequences of
      discontinuous resource use for limiting similarity, species diversity, and trait
      dispersion.
AB  - The recently proposed tolerance-fecundity trade-off model represents a step
      forward in the study of seed size diversity in plant communities. However, it
      uses an oversimplified picture of seed tolerance, with an infinitely sharp
      threshold: the probability that a seed tolerate a given stress level is either 1
      or 0. This invites a revision of the model, presented here. We demonstrate that
      this simplification has large impacts on model behavior, including altering
      predictions regarding limiting similarity, raising expected diversity levels, and
      lessening expected spacing between species along the trait axis. Such dramatic
      impacts ultimately stem from the fact that a discontinuity in the probability of
      tolerating a site drastically reduces competition between similar species. This
      is one example of a class of models with a nondifferentiable peak in the
      competition kernel, which we recently showed is produced by resource use
      unrealistically modeled as discontinuous and affects fundamental predictions
      regarding limiting similarity. This article illustrates those general results and
      offers a revised model of the tolerance-fecundity trade-off.

PMID- 23535626
TI  - Public mental health--what is to be done?

PMID- 23535627
TI  - Usefulness of the Hospital Anxiety and Depression Scale for screening for
      psychiatric morbidity in Chinese patients with Graves' ophthalmopathy.
AB  - OBJECTIVE: To examine the usefulness of the Hospital Anxiety and Depression Scale
      (HADS) for screening psychiatric morbidity in Chinese patients with Graves'
      ophthalmopathy. METHODS: A cross-sectional study was conducted from 1 January
      2010 to 31 December 2010 at the specialist eye outpatient clinic at Pamela Youde
      Nethersole Eastern Hospital. All euthyroid patients diagnosed with Graves'
      ophthalmopathy were recruited. They were interviewed with the Chinese version of
      the HADS and the Structured Clinical Interview for the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition Axis I. Demographic data and clinical
      background information were collected from the patients and their hospital
      records were reviewed. RESULTS: In all, 124 patients were recruited into the
      study. Current prevalence of psychiatric disorders was 32%, of which 19% were
      current depressive disorders and 19% were current anxiety disorders. The HADS
      provided the best discriminating power for screening for psychiatric morbidity at
      a cut-off threshold of 10/11. For screening of depressive and anxiety disorders,
      the cut-off thresholds were 4/5 and 6/7 respectively. CONCLUSION: Depression and
      anxiety disorders were common in the local population of patients with Graves'
      ophthalmopathy. Recognising the predictors for psychiatric morbidity could assist
      clinicians to identify those patients with a predisposition to developing
      psychiatric complications, and refer them for appropriate treatment. The HADS can
      be considered as a screening tool for psychiatric morbidity in patients with
      Graves' ophthalmopathy.

PMID- 23535628
TI  - Attitudes in the management of patients with dementia: comparison in doctors with
      and without special training.
AB  - OBJECTIVE: To explore by postal survey the different attitudes towards management
      of patients with dementia in physicians with and without dementia training.
      METHODS: A questionnaire was sent to 7669 members of the Hong Kong Medical
      Association, which represents 61% of all locally registered medical
      practitioners. RESULTS: In all, 448 questionnaires were returned (response rate:
      6%). Among these, there were 34 questionnaires with missing data or the
      respondents indicated that they were either retired or not in practice.
      Therefore, only 414 questionnaires were used in analysis. Among these, 82 (20%)
      had received dementia training, 310 (75%) had not, and 22 (5%) did not indicate
      their choice. Twelve statements were used to explore various attitudes about
      dementia care. Exploratory factor analysis showed that there were 2 strong
      factors: confidence and negative views. The mean scores of these 2 factors were
      significantly different in physicians with and without dementia training. With
      respect to management of patients with dementia, dementia-trained physicians had
      significantly greater confidence (mean [standard deviation (SD)] = 5.21 [1.34])
      than those who were non-trained (mean [SD] = 3.57 [1.40]; p < 0.001). Conversely,
      non-trained physicians had significantly stronger negative views (mean [SD] =
      3.89 [1.24]) on dementia care than those who were trained (mean [SD] = 3.12
      [1.36]; p < 0.001). DISCUSSION: These findings suggest that providing a certain
      level of dementia care training for physicians is an effective way to improve
      confidence in managing patients with dementia, and thereby decrease possible
      negative attitudes towards such care.

PMID- 23535629
TI  - Metabolic complications of schizophrenia and antipsychotic medications--an
      updated review.
AB  - Metabolic syndrome is a cluster of risk factors comprising obesity,
      dyslipidaemias, glucose intolerance, insulin resistance (or hyperinsulinaemia),
      and hypertension, and is highly predictive of type 2 diabetes mellitus and
      cardiovascular disease. The life expectancy of people with schizophrenia is
      reduced by 20%, with 60% of the excess mortality due to physical illness.
      Schizophrenia itself may be a risk factor for metabolic syndrome and there is
      also increasing concern that antipsychotic drugs, particularly second-generation
      antipsychotics, have metabolic consequences that contribute to the risk. Various
      diagnostic guidelines, updated facts with regard to epidemiology,
      pathophysiology, risk factors, and complications of metabolic syndrome are
      discussed in this review. Moreover, the impact of various antipsychotics on
      metabolic syndrome and their possible mechanisms are comprehensively reviewed.
      The authors emphasise that, while many adults with schizophrenia receive little
      or no medical care, such care is important given the risk of metabolic
      abnormalities associated not only with antipsychotic medications, but also with
      schizophrenia in general.

PMID- 23535630
TI  - The Center For Medicare And Medicaid Innovation's blueprint for rapid-cycle
      evaluation of new care and payment models.
AB  - The Affordable Care Act established the Center for Medicare and Medicaid
      Innovation to test innovative payment and service delivery models. The goal is to
      reduce program expenditures while preserving or improving the quality of care
      provided to beneficiaries of Medicare, Medicaid, and the Children's Health
      Insurance Program. Central to the success of the Innovation Center is a new,
      rapid-cycle approach to evaluation. This article describes that approach--setting
      forth how the Rapid Cycle Evaluation Group aims to deliver frequent feedback to
      providers in support of continuous quality improvement, while rigorously
      evaluating the outcomes of each model tested. This article also describes the
      relationship between the group's work and that of the Office of the Actuary at
      the Centers for Medicare and Medicaid Services, which plays a central role in the
      assessment of new models.

PMID- 23535631
TI  - Polyoxometalate-based purely inorganic porous frameworks with selective
      adsorption and oxidative catalysis functionalities.
AB  - Purely inorganic porous frameworks using catalytically active [MnV13O38](7-)
      clusters as nodes and rare earth ions as linkers have been successfully prepared.
      The POM-based porous framework is a kind of multifunctional material, which
      exhibits selective adsorption behavior and remarkable catalytic activity for the
      heterogeneous oxidation of sulfides.

PMID- 23535632
TI  - Oligonucleotide assisted light-emitting Alq3 microrods: energy transfer effect
      with fluorescent dyes.
AB  - Oligonucleotide assisted tri(8-hydroxyquinoline) aluminium (Alq3) microrods were
      prepared for the first time. When hybridized with oligonucleotide labeled by Cy3
      fluorescent dye, a significant photoluminescence variation of the Alq3 microrods
      was observed due to Forster resonance energy transfer, unlike when Cy5
      oligonucleotide was used. Versatile nucleotide manipulation would open up wider
      applications of Alq3-based materials, based on this fundamental observation.

PMID- 23535633
TI  - Liquid chromatography-high-resolution mass spectrometry for pesticide residue
      analysis in fruit and vegetables: screening and quantitative studies.
AB  - This work reviews the current state-of-the-art of liquid chromatography coupled
      to high-resolution mass spectrometry (LC-HRMS) techniques applied to the analysis
      of pesticides in fruit-based and vegetable-based matrices. Nowadays, simultaneous
      trace analysis of hundreds of pesticides from different classes is required,
      preferably in just one run. The most commonly used QqQ-MS technology presents
      certain limitations in its application in a cost and effective way when analyzing
      a large number of pesticides. Thus, this review includes HRMS technology as a
      reliable complementary alternative allowing the analysis of a wide range of
      pesticides in food. Its capabilities and limitations in identifying, confirming
      and quantifying pesticides are discussed. HRMS instruments can adequately address
      such issues; however, the main drawbacks are as a result of insufficient prior
      optimization of the operational parameters during non-target analysis in full
      scan mode and due to software shortcomings.

PMID- 23535634
TI  - FBAR syndapin 1 recognizes and stabilizes highly curved tubular membranes in a
      concentration dependent manner.
AB  - Syndapin 1 FBAR, a member of the Bin-amphiphysin-Rvs (BAR) domain protein family,
      is known to induce membrane curvature and is an essential component in biological
      processes like endocytosis and formation and growth of neurites. We quantify the
      curvature sensing of FBAR on reconstituted porcine brain lipid vesicles and show
      that it senses membrane curvature at low density whereas it induces and
      reinforces tube stiffness at higher density. FBAR strongly up-concentrates on the
      high curvature tubes pulled out of Giant Unilamellar lipid Vesicles (GUVs), this
      sorting behavior is strongly amplified at low protein densities. Interestingly,
      FBAR from syndapin 1 has a large affinity for tubular membranes with curvatures
      larger than its own intrinsic concave curvature. Finally, we studied the effect
      of FBAR on membrane relaxation kinetics with high temporal resolution and found
      that the protein increases relaxation time of the tube holding force in a density
      dependent fashion.

PMID- 23535635
TI  - Different approaches to estimate exposure to work stressors, using repeated
      measurements, and the association with cardiovascular disease.
AB  - OBJECTIVE: To explore the stability of exposure to work stressors over time and
      to examine the impact of different approaches of estimating exposure on the
      cardiovascular disease (CVD) risk estimation. METHODS: The Maastricht Cohort
      Study-Work Stressor Score was used to assess work stressors at three consecutive
      time points among 6154 employees participating in the Maastricht Cohort Study.
      Incident CVD was assessed with questionnaires. Five approaches were used to
      estimate exposure as, for example, cumulative exposure above a cutoff point,
      total exposure, and average exposure. RESULTS: The correlation between the work
      stressor scores assessed at the first and third time point was 0.58. Employees
      with a stable exposure above the highest quartile had a fully adjusted hazard
      ratio of 1.58 (95% confidence interval, 0.93 to 2.72). CONCLUSION: Employees with
      a stable exposure above the highest quartile score during a minimum of 2 years
      might have the highest relative CVD risk.

PMID- 23535636
TI  - Fabrication quality analysis of a fiber optic refractive index sensor created by
      CO2 laser machining.
AB  - This study investigates the CO2 laser-stripped partial cladding of silica-based
      optic fibers with a core diameter of 400 MUm, which enables them to sense the
      refractive index of the surrounding environment. However, inappropriate
      treatments during the machining process can generate a number of defects in the
      optic fiber sensors. Therefore, the quality of optic fiber sensors fabricated
      using CO2 laser machining must be analyzed. The results show that analysis of the
      fiber core size after machining can provide preliminary defect detection, and
      qualitative analysis of the optical transmission defects can be used to identify
      imperfections that are difficult to observe through size analysis. To more
      precisely and quantitatively detect fabrication defects, we included a tensile
      test and numerical aperture measurements in this study. After a series of quality
      inspections, we proposed improvements to the existing CO2 laser machining
      parameters, namely, a vertical scanning pathway, 4 W of power, and a feed rate of
      9.45 cm/s. Using these improved parameters, we created optical fiber sensors with
      a core diameter of approximately 400 MUm, no obvious optical transmission
      defects, a numerical aperture of 0.52 +/- 0.019, a 0.886 Weibull modulus, and a
      1.186 Weibull-shaped parameter. Finally, we used the optical fiber sensor
      fabricated using the improved parameters to measure the refractive indices of
      various solutions. The results show that a refractive-index resolution of 1.8 *
      10(-4) RIU (linear fitting R2 = 0.954) was achieved for sucrose solutions with
      refractive indices ranging between 1.333 and 1.383. We also adopted the particle
      plasmon resonance sensing scheme using the fabricated optical fibers. The results
      provided additional information, specifically, a superior sensor resolution of
      5.73 * 10(-5) RIU, and greater linearity at R2 = 0.999.

PMID- 23535637
TI  - High S/N ratio slotted step piezoresistive microcantilever designs for
      biosensors.
AB  - This study proposes new microcantilever designs in slotted step configuration to
      improve the S/N ratio of surface stress-based sensors used in physical, chemical,
      biochemical and biosensor applications. The cantilevers are made of silicon
      dioxide with a u-shaped silicon piezoresistor in p-doped. The cantilever step
      length and piezoresistor length is varied along with the operating voltage to
      characterise the surface stress sensitivity and thermal drifting sensitivity of
      the cantilevers when used as immunosensor. The numerical analysis is performed
      using ANSYS Multiphysics. Results show the surface stress sensitivity and the S/N
      ratio of the slotted step cantilevers is improved by more than 32% and 22%,
      respectively, over its monolithic counterparts.

PMID- 23535638
TI  - Frame synchronization of high-speed vision sensors with respect to temporally
      encoded illumination in highly dynamic environments.
AB  - The authors propose a Manchester Encoding inspired illumination modulation
      strategy to properly index the temporally-aligned vision frames, which are
      successfully synchronized by the LED reference signal. Based on signal
      normalization, Manchester Encoded reference signals carry temporal information
      owing to serial communication and thus can timestamp the output vision frame.
      Both simulated and experimental results show satisfactory robustness to various
      disturbances, such as dynamic targets, fluctuant optical intensity, and unfixed
      cameras, etc. The 1,000 Hz vision sensor is locked to 500 Hz temporally modulated
      LED illumination with only 24 MUs jitters. This result is believed to be
      applicable to low-cost wireless vision sensor network.

PMID- 23535640
TI  - Anti-viral activity of galectin-1 from flounder Paralichthys olivaceus.
AB  - Galectins are a family of Ca(2+)-independent soluble lectins characterized by
      their affinity to beta-galactosides. Mammalian galectins have been shown to play
      a defense role against certain bacteria, fungi and viruses. However, the
      immunological functions of galectins in fish is poorly characterized. Here we
      demonstrated that the expression of galectin-1 gene from the flounder
      Paralichthys olivaceus was decreased in the initial 8 h after challenge with poly
      I:C, then increased markedly from 24 h onwards, and the recombinant galectin-1
      was able to neutralize the lymphocystis disease virus (LCDV), inhibiting the
      formation of cytopathic effects. In addition, the recombinant galectin had a
      potential anti-inflammatory activity against infection by LCDV, and was able to
      restrain the overexpression of the anti-viral protein gene mx against virus
      infection. These results indicate that flounder galectin-1 has an anti-viral
      activity, capable of reducing LCDV pathogenicity.

PMID- 23535641
TI  - Magnetic order in a frustrated two-dimensional atom lattice at a semiconductor
      surface.
AB  - Two-dimensional electron systems, as exploited for device applications, can lose
      their conducting properties because of local Coulomb repulsion, leading to a Mott
      insulating state. In triangular geometries, any concomitant antiferromagnetic
      spin ordering can be prevented by geometric frustration, spurring speculations
      about 'melted' phases, known as spin liquid. Here we show that for a realization
      of a triangular electron system by epitaxial atom adsorption on a semiconductor,
      such spin disorder, however, does not appear. Our study compares the electron
      excitation spectra obtained from theoretical simulations of the correlated
      electron lattice with data from high-resolution photoemission. We find that an
      unusual row-wise antiferromagnetic spin alignment occurs that is reflected in the
      photoemission spectra as characteristic 'shadow bands' induced by the spin
      pattern. The magnetic order in a frustrated lattice of otherwise non-magnetic
      components emerges from longer-range electron hopping between the atoms. This
      finding can offer new ways of controlling magnetism on surfaces.

PMID- 23535642
TI  - European origin of placodont marine reptiles and the evolution of crushing
      dentition in Placodontia.
AB  - Sauropterygia was the most successful marine reptile radiation in history,
      spanning almost the entire Mesozoic and exploiting a wide range of habitats and
      ecological niches. Here we report a new, exceptionally preserved skull of a
      juvenile stem placodont from the early Middle Triassic of the Netherlands, thus
      indicating a western Tethyan (European) origin for Placodontia, the most basal
      group of sauropterygians. A single row of teeth on an enlarged palatine supports
      this close relationship, although these are small and pointed instead of broad
      and flat, as is the case in placodonts, which demonstrate the strongest
      adaptation to a durophagous diet known in any reptile. Peg-like, slightly
      procumbent premaxillary teeth and an 'L-shaped' jugal also confirm a close
      relationship to basal placodonts. The new taxon provides insight into the
      evolution of placodont dentition, representing a transitional morphology between
      the plesiomorphic diapsid condition of palatal denticles and the specialized
      crushing teeth of placodonts.

PMID- 23535643
TI  - Significant performance enhancement in photoconductive terahertz optoelectronics
      by incorporating plasmonic contact electrodes.
AB  - Even though the terahertz spectrum is well suited for chemical identification,
      material characterization, biological sensing and medical imaging, practical
      development of these applications has been hindered by attributes of existing
      terahertz optoelectronics. Here we demonstrate that the use of plasmonic contact
      electrodes can significantly mitigate the low-quantum efficiency performance of
      photoconductive terahertz optoelectronics. The use of plasmonic contact
      electrodes offers nanoscale carrier transport path lengths for the majority of
      photocarriers, increasing the number of collected photocarriers in a
      subpicosecond timescale and, thus, enhancing the optical-to-terahertz conversion
      efficiency of photoconductive terahertz emitters and the detection sensitivity of
      photoconductive terahertz detectors. We experimentally demonstrate 50 times
      higher terahertz radiation powers from a plasmonic photoconductive emitter in
      comparison with a similar photoconductive emitter with non-plasmonic contact
      electrodes, as well as 30 times higher terahertz detection sensitivities from a
      plasmonic photoconductive detector in comparison with a similar photoconductive
      detector with non-plasmonic contact electrodes.

PMID- 23535644
TI  - Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells.
AB  - While chromosomal translocations have a fundamental role in the development of
      several human leukaemias, their role in solid tumour development has been
      somewhat more controversial. Recently, it was shown that up to 80% of prostate
      tumours harbour at least one such gene fusion, and that the most common fusion
      event, between the prostate-specific TMPRSS2 gene and the ERG oncogene, is a
      critical, and probably early factor in prostate cancer development. Here we
      demonstrate the presence and expression of this significant chromosomal
      rearrangement in prostate cancer stem cells. Moreover, we show that in the
      prostate epithelial hierarchy from both normal and tumour tissues, TMPRSS2
      transcription is subjected to tight monoallelic regulation, which is retained
      upon asymmetric division and relaxed during epithelial cell differentiation. The
      presence and expression of TMPRSS2/ERG in prostate stem cells would provide ERG
      driven survival advantages, allowing maintenance of this mutated genotype.

PMID- 23535645
TI  - Controlled charge trapping by molybdenum disulphide and graphene in ultrathin
      heterostructured memory devices.
AB  - Atomically thin two-dimensional materials have emerged as promising candidates
      for flexible and transparent electronic applications. Here we show non-volatile
      memory devices, based on field-effect transistors with large hysteresis,
      consisting entirely of stacked two-dimensional materials. Graphene and molybdenum
      disulphide were employed as both channel and charge-trapping layers, whereas
      hexagonal boron nitride was used as a tunnel barrier. In these ultrathin
      heterostructured memory devices, the atomically thin molybdenum disulphide or
      graphene-trapping layer stores charge tunnelled through hexagonal boron nitride,
      serving as a floating gate to control the charge transport in the graphene or
      molybdenum disulphide channel. By varying the thicknesses of two-dimensional
      materials and modifying the stacking order, the hysteresis and conductance
      polarity of the field-effect transistor can be controlled. These devices show
      high mobility, high on/off current ratio, large memory window and stable
      retention, providing a promising route towards flexible and transparent memory
      devices utilizing atomically thin two-dimensional materials.

PMID- 23535646
TI  - Rotational separation of non-spherical bioparticles using I-shaped pillar arrays
      in a microfluidic device.
AB  - Most bioparticles, such as red blood cells and bacteria, are non-spherical in
      shape. However, conventional microfluidic separation devices are designed for
      spherical particles. This poses a challenge in designing a separation device for
      non-spherical bioparticles, as the smallest dimension of the bioparticle has to
      be considered, which increases fabrication challenges and decreases the
      throughput. If current methods do not take into account the shape of non
      spherical bioparticles, the separation will be inefficient. Here, to address this
      challenge, we present a novel technique for the separation of red blood cells as
      a non-spherical bioparticle, using a new I-shaped pillar arrays design. It takes
      the shape into account and induces rotational movements, allowing us to leverage
      on the largest dimension, which increases its separation size. This technique has
      been used for 100% separation of red blood cells from blood samples in a focused
      stream, outperforming the conventional pillar array designs.

PMID- 23535647
TI  - Sulfhydration mediates neuroprotective actions of parkin.
AB  - Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3
      ligase, parkin, in the brains of patients with Parkinson's disease are thought to
      be pathogenic and suggest a possible mechanism linking parkin to sporadic
      Parkinson's disease. Here we demonstrate that physiologic modification of parkin
      by hydrogen sulfide, termed sulfhydration, enhances its catalytic activity.
      Sulfhydration sites are identified by mass spectrometry analysis and are
      investigated by site-directed mutagenesis. Parkin sulfhydration is markedly
      depleted in the brains of patients with Parkinson's disease, suggesting that this
      loss may be pathologic. This implies that hydrogen sulfide donors may be
      therapeutic.

PMID- 23535650
TI  - Impaired endolysosomal function disrupts Notch signalling in optic nerve
      astrocytes.
AB  - Astrocytes migrate from the optic nerve into the inner retina, forming a template
      upon which retinal vessels develop. In the Nuc1 rat, mutation in the gene
      encoding betaA3/A1-crystallin disrupts both Notch signalling in astrocytes and
      formation of the astrocyte template. Here we show that loss of betaA3/A1
      crystallin in astrocytes does not impede Notch ligand binding or extracellular
      cleavages. However, it affects vacuolar-type proton ATPase (V-ATPase) activity,
      thereby compromising acidification of the endolysosomal compartments, leading to
      reduced gamma-secretase-mediated processing and release of the Notch
      intracellular domain (NICD). Lysosomal-mediated degradation of Notch is also
      impaired. These defects decrease the level of NICD in the nucleus, inhibiting the
      expression of Notch target genes. Overexpression of betaA3/A1-crystallin in those
      same astrocytes restored V-ATPase activity and normal endolysosomal
      acidification, thereby increasing the levels of gamma-secretase to facilitate
      optimal Notch signalling. We postulate that betaA3/A1-crystallin is essential for
      normal endolysosomal acidification, and thereby, normal activation of Notch
      signalling in astrocytes.

PMID- 23535651
TI  - Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission
      with intestinal slow-wave activity.
AB  - The enteric nervous system contains excitatory and inhibitory neurons, which
      control contraction and relaxation of smooth muscle cells as well as
      gastrointestinal motor activity. Little is known about the exact cellular
      mechanisms of neuronal signal transduction to smooth muscle cells in the gut.
      Here we generate a c-Kit(CreERT2) knock-in allele to target a distinct population
      of pacemaker cells called interstitial cells of Cajal. By genetic loss-of
      function studies, we show that interstitial cells of Cajal, which generate
      spontaneous electrical slow waves and thus rhythmic contractions of the smooth
      musculature, are essential for transmission of signals from enteric neurons to
      gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore,
      integrate excitatory and inhibitory neurotransmission with slow-wave activity to
      orchestrate peristaltic motor activity of the gut. Impairment of the function of
      interstitial cells of Cajal causes severe gastrointestinal motor disorders. The
      results of our study show at the genetic level that these disorders are not only
      due to loss of slow-wave activity but also due to disturbed neurotransmission.

PMID- 23535652
TI  - Biased Brownian stepping rotation of FoF1-ATP synthase driven by proton motive
      force.
AB  - FoF1-ATP synthase (FoF1) produces most of the ATP in cells, uniquely, by
      converting the proton motive force (pmf) into ATP production via mechanical
      rotation of the inner rotor complex. Technical difficulties have hampered direct
      investigation of pmf-driven rotation, which are crucial to elucidating the
      chemomechanical coupling mechanism of FoF1. Here we develop a novel supported
      membrane system for direct observation of the rotation of FoF1 driven by pmf that
      was formed by photolysis of caged protons. Upon photolysis, FoF1 initiated
      rotation in the opposite direction to that of the ATP-driven rotation. The step
      size of pmf-driven rotation was 120 degrees , suggesting that the kinetic
      bottleneck is a catalytic event on F1 with threefold symmetry. The reaction
      equilibrium was slightly biased to ATP synthesis like under physiological
      conditions, and FoF1 showed highly stochastic behaviour, frequently making a 120
      degrees  backward step. This new experimental system would be applicable to
      single-molecule study of other membrane proteins.

PMID- 23535653
TI  - Unusually stable ~100-fold reversible and instantaneous swelling of inorganic
      layered materials.
AB  - Cells can swell or shrink in certain solutions; however, no equivalent activity
      has been observed in inorganic materials. Although lamellar materials exhibit
      increased volume with increase in the lamellar period, the interlamellar
      expansion is usually limited to a few nanometres, with a simultaneous partial or
      complete exfoliation into individual atomic layers. Here we demonstrate a large
      monolithic crystalline swelling of layered materials. The gallery spacing can be
      instantly increased ~100-fold in one direction to ~90 nm, with the neighbouring
      layers separated primarily by H2O. The layers remain strongly held without
      peeling or translational shifts, maintaining a nearly perfect three-dimensional
      lattice structure of >3,000 layers. First-principle calculations yield a long
      range directional structuring of the H2O molecules that may help to stabilize the
      highly swollen structure. The crystals can also instantaneously shrink back to
      their original sizes. These findings provide a benchmark for understanding the
      exfoliating layered materials.

PMID- 23535654
TI  - High performance piezoelectric devices based on aligned arrays of nanofibers of
      poly(vinylidenefluoride-co-trifluoroethylene).
AB  - Multifunctional capability, flexible design, rugged lightweight construction and
      self-powered operation are desired attributes for electronics that directly
      interface with the human body or with advanced robotic systems. For these
      applications, piezoelectric materials, in forms that offer the ability to bend
      and stretch, are attractive for pressure/force sensors and mechanical energy
      harvesters. Here, we introduce a large area, flexible piezoelectric material that
      consists of sheets of electrospun fibres of the polymer poly[(vinylidenefluoride
      co-trifluoroethylene]. The flow and mechanical conditions associated with the
      spinning process yield free-standing, three-dimensional architectures of aligned
      arrangements of such fibres, in which the polymer chains adopt strongly
      preferential orientations. The resulting material offers exceptional
      piezoelectric characteristics, to enable ultra-high sensitivity for measuring
      pressure, even at exceptionally small values (0.1 Pa). Quantitative analysis
      provides detailed insights into the pressure sensing mechanisms, and establishes
      engineering design rules. Potential applications range from self-powered micro
      mechanical elements, to self-balancing robots and sensitive impact detectors.

PMID- 23535655
TI  - Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees.
AB  - Pesticides that target cholinergic neurotransmission are highly effective, but
      their use has been implicated in insect pollinator population decline. Honeybees
      are exposed to two widely used classes of cholinergic pesticide: neonicotinoids
      (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase
      inhibitors). Although sublethal levels of neonicotinoids are known to disrupt
      honeybee learning and behaviour, the neurophysiological basis of these effects
      has not been shown. Here, using recordings from mushroom body Kenyon cells in
      acutely isolated honeybee brain, we show that the neonicotinoids imidacloprid and
      clothianidin, and the organophosphate miticide coumaphos oxon, cause a
      depolarization-block of neuronal firing and inhibit nicotinic responses. These
      effects are observed at concentrations that are encountered by foraging honeybees
      and within the hive, and are additive with combined application. Our findings
      demonstrate a neuronal mechanism that may account for the cognitive impairments
      caused by neonicotinoids, and predict that exposure to multiple pesticides that
      target cholinergic signalling will cause enhanced toxicity to pollinators.

PMID- 23535648
TI  - Identification and molecular characterization of a new ovarian cancer
      susceptibility locus at 17q21.31.
AB  - Epithelial ovarian cancer (EOC) has a heritable component that remains to be
      fully characterized. Most identified common susceptibility variants lie in non
      protein-coding sequences. We hypothesized that variants in the 3' untranslated
      region at putative microRNA (miRNA)-binding sites represent functional targets
      that influence EOC susceptibility. Here, we evaluate the association between 767
      miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174
      EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative
      Oncological Gene-environment Study. We identify several miRSNPs associated with
      invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion
      polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31
      reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31
      is associated with neurological diseases, and our collaboration is the first to
      report an association with EOC susceptibility. An integrated molecular analysis
      in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC
      susceptibility genes.

PMID- 23535657
TI  - Effective localized collection and identification of airborne species through
      electrodynamic precipitation and SERS-based detection.
AB  - Various nanostructured sensor designs currently aim to achieve or claim single
      molecular detection by a reduction of the active sensor size. However, a
      reduction of the sensor size has the negative effect of reducing the capture
      probability considering the diffusion-based analyte transport commonly used. Here
      we introduce and apply a localized programmable electrodynamic precipitation
      concept as an alternative to diffusion. The process provides higher collection
      rates of airborne species and detection at lower concentration. As an example, we
      compare an identical nanostructured surfaced-enhanced Raman spectroscopy sensor
      with and without localized delivery and find that the sensitivity and detection
      time is improved by at least two orders of magnitudes. Localized collection in an
      active-matrix array-like fashion is also tested, yielding hybrid molecular arrays
      on a single chip over a broad range of molecular weights, including small
      benzenethiol (110.18 Da) and 4-fluorobenzenethiol (128.17 Da), or large
      macromolecules such as anti-mouse IgG (~150 kDa).

PMID- 23535656
TI  - Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and
      -independent mechanisms.
AB  - The generation of neurons by neural stem cells is a highly choreographed process
      that requires extensive and dynamic remodelling of the cytoskeleton at each step
      of the process. The atypical RhoGTPase Rnd3 is expressed by progenitors in the
      embryonic brain but its role in early steps of neurogenesis has not been
      addressed. Here we show that silencing Rnd3 in the embryonic cerebral cortex
      interferes with the interkinetic nuclear migration of radial glial stem cells,
      disrupts their apical attachment and modifies the orientation of their cleavage
      plane. These defects are rescued by co-expression of a constitutively active form
      of cofilin, demonstrating that Rnd3-mediated disassembly of actin filaments
      coordinates the cellular behaviour of radial glial. Rnd3 also limits the
      divisions of basal progenitors via a distinct mechanism involving the suppression
      of cyclin D1 translation. Interestingly, although Rnd3 expression is controlled
      transcriptionally by Ascl1, this proneural factor is itself required in radial
      glial progenitors only for proper orientation of cell divisions.

PMID- 23535649
TI  - Epigenetic analysis leads to identification of HNF1B as a subtype-specific
      susceptibility gene for ovarian cancer.
AB  - HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed
      epigenetic silencing in serous epithelial ovarian cancer, leading us to
      hypothesize that variation in this gene differentially associates with epithelial
      ovarian cancer risk according to histological subtype. Here we comprehensively
      map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse
      DNA methylation and expression profiles across histological subtypes. Different
      single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds
      ratio (OR)=1.13, P=3.1 * 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 * 10(
      8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with
      higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed
      HNF1B, primarily present in clear cell tumours, coincides with a CpG island
      methylator phenotype affecting numerous other promoters throughout the genome.
      Different variants in HNF1B associate with risk of serous and clear cell
      epithelial ovarian cancer; DNA methylation and expression patterns are also
      notably distinct between these subtypes. These findings underscore distinct
      mechanisms driving different epithelial ovarian cancer histological subtypes.

PMID- 23535658
TI  - Probing transcription factor diffusion dynamics in the living mammalian embryo
      with photoactivatable fluorescence correlation spectroscopy.
AB  - Transcription factors use diffusion to search the DNA, yet the mechanisms
      controlling transcription factor diffusion during mammalian development remain
      poorly understood. Here we combine photoactivation and fluorescence correlation
      spectroscopy to study transcription factor diffusion in developing mouse embryos.
      We show that the pluripotency-associated transcription factor Oct4 displays both
      fast and Brownian and slower subdiffusive behaviours that are controlled by DNA
      interactions. Following cell lineage specification, the slower DNA-interacting
      diffusion fraction distinguishes pluripotent from extraembryonic cell nuclei.
      Similar to Oct4, Sox2 shows slower diffusion in pluripotent cells while Cdx2
      displays opposite dynamics, suggesting that slow diffusion may represent a
      general feature of transcription factors in lineages where they are essential.
      Slow Oct4 subdiffusive behaviours are conserved in embryonic stem cells and
      induced pluripotent stem cells (iPS cells), and lost during differentiation. We
      also show that Oct4 diffusion depends on its interaction with ERG-associated
      protein with SET domain. Photoactivation and fluorescence correlation
      spectroscopy provides a new intravital approach to study transcription factor
      diffusion in complex in vivo systems.

PMID- 23535659
TI  - Expansion of host cellular niche can drive adaptation of a zoonotic malaria
      parasite to humans.
AB  - The macaque malaria parasite Plasmodium knowlesi has recently emerged as an
      important zoonosis in Southeast Asia. Infections are typically mild but can cause
      severe disease, achieving parasite densities similar to fatal Plasmodium
      falciparum infections. Here we show that a primate-adapted P. knowlesi parasite
      proliferates poorly in human blood due to a strong preference for young red blood
      cells (RBCs). We establish a continuous in vitro culture system by using human
      blood enriched for young cells. Mathematical modelling predicts that parasite
      adaptation for invasion of older RBCs is a likely mechanism leading to high
      parasite densities in clinical infections. Consistent with this model, we find
      that P. knowlesi can adapt to invade a wider age range of RBCs, resulting in
      proliferation in normal human blood. Such cellular niche expansion may increase
      pathogenesis in humans and will be a key feature to monitor as P. knowlesi
      emerges in human populations.

PMID- 23535660
TI  - Trunk exoskeleton in teleosts is mesodermal in origin.
AB  - The vertebrate mineralized skeleton is known to have first emerged as an
      exoskeleton that extensively covered the fossil jawless fish. The evolutionary
      origin of this exoskeleton has long been attributed to the emergence of the
      neural crest, but experimental evaluation for this is still poor. Here we
      determine the embryonic origin of scales and fin rays of medaka (teleost trunk
      exoskeletons) by applying long-term cell labelling methods, and demonstrate that
      both tissues are mesodermal in origin. Neural crest cells, however, fail to
      contribute to these tissues. This result suggests that the trunk neural crest has
      no skeletogenic capability in fish, instead highlighting the dominant role of the
      mesoderm in the evolution of the trunk skeleton. This further implies that the
      role of the neural crest in skeletogenesis has been predominant in the cephalic
      region from the early stage of vertebrate evolution.

PMID- 23535661
TI  - Broadband phonon mean free path contributions to thermal conductivity measured
      using frequency domain thermoreflectance.
AB  - Non-metallic crystalline materials conduct heat by the transport of quantized
      atomic lattice vibrations called phonons. Thermal conductivity depends on how far
      phonons travel between scattering events-their mean free paths. Due to the
      breadth of the phonon mean free path spectrum, nanostructuring materials can
      reduce thermal conductivity from bulk by scattering long mean free path phonons,
      whereas short mean free path phonons are unaffected. Here we use a breakdown in
      diffusive phonon transport generated by high-frequency surface temperature
      modulation to identify the mean free path-dependent contributions of phonons to
      thermal conductivity in crystalline and amorphous silicon. Our measurements probe
      a broad range of mean free paths in crystalline silicon spanning 0.3-8.0 MUm at a
      temperature of 311 K and show that 40+/-5% of its thermal conductivity comes from
      phonons with mean free path >1 MUm. In a 500 nm thick amorphous silicon film,
      despite atomic disorder, we identify propagating phonon-like modes that
      contribute >35+/-7% to thermal conductivity at a temperature of 306 K.

PMID- 23535662
TI  - CSN- and CAND1-dependent remodelling of the budding yeast SCF complex.
AB  - Cullin-RING ligases (CRLs) are ubiquitin E3 enzymes with variable substrate
      adaptor and -receptor subunits. All CRLs are activated by modification of the
      cullin subunit with the ubiquitin-like protein Nedd8 (neddylation). The protein
      CAND1 (Cullin-associated-Nedd8-dissociated-1) also promotes CRL activity, even
      though it only interacts with inactive ligase complexes. The molecular mechanism
      underlying this behaviour remains largely unclear. Here, we find that yeast SCF
      (Skp1-Cdc53-F-box) Cullin-RING complexes are remodelled in a CAND1-dependent
      manner, when cells are switched from growth in fermentable to non-fermentable
      carbon sources. Mechanistically, CAND1 promotes substrate adaptor release
      following SCF deneddylation by the COP9 signalosome (CSN). CSN- or CAND1-mutant
      cells fail to release substrate adaptors. This delays the formation of new
      complexes during SCF reactivation and results in substrate degradation defects.
      Our results shed light on how CAND1 regulates CRL activity and demonstrate that
      the cullin neddylation-deneddylation cycle is not only required to activate CRLs,
      but also to regulate substrate specificity through dynamic substrate adaptor
      exchange.

PMID- 23535663
TI  - CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire.
AB  - The combinatorial architecture of cullin 1-RING ubiquitin ligases, in which
      multiple F-box containing substrate receptors compete for access to CUL1, poses
      special challenges to assembling cullin 1-RING ubiquitin ligase complexes through
      high affinity protein interactions while maintaining the flexibility to
      dynamically sample the entire F-box containing substrate receptor repertoire.
      Here, using highly quantitative mass spectrometry, we demonstrate that this
      problem is addressed by CAND1, a factor that controls the dynamics of the global
      cullin 1-RING ubiquitin ligase network by promoting the assembly of newly
      synthesized F-box containing substrate receptors with CUL1-RBX1 core complexes.
      Our studies of in vivo cullin 1-RING ubiquitin ligase dynamics and in vitro
      biochemical findings showing that CAND1 can displace F-box containing substrate
      receptors from Cul1p suggest that CAND1 functions in a cycle that serves to
      exchange F-box containing substrate receptors on CUL1 cores. We propose that this
      cycle assures comprehensive sampling of the entire F-box containing substrate
      receptor repertoire in order to maintain the cullin 1-RING ubiquitin ligase
      landscape, a function that we show to be critical for substrate degradation and
      normal physiology.

PMID- 23535664
TI  - Narrowband photodetection in the near-infrared with a plasmon-induced hot
      electron device.
AB  - In gratings, incident light can couple strongly to plasmons propagating through
      periodically spaced slits in a metal film, resulting in a strong, resonant
      absorption whose frequency is determined by the nanostructure periodicity. When a
      grating is patterned on a silicon substrate, the absorption response can be
      combined with plasmon-induced hot electron photocurrent generation. This yields a
      photodetector with a strongly resonant, narrowband photocurrent response in the
      infrared, limited at low frequencies by the Schottky barrier, not the bandgap of
      silicon. Here we report a grating-based hot electron device with significantly
      larger photocurrent responsivity than previously reported antenna-based
      geometries. The grating geometry also enables more than three times narrower
      spectral response than observed for nanoantenna-based devices. This approach
      opens up the possibility of plasmonic sensors with direct electrical readout,
      such as an on-chip surface plasmon resonance detector driven at a single
      wavelength.

PMID- 23535666
TI  - Poole-Frenkel effect in sputter-deposited CuAlO(2+x) nanocrystals.
AB  - Field-assisted thermionic emission within a sputter-deposited, nanocrystalline
      thin film of CuAlO2.06 is observed for the first time, and explained in terms of
      the Poole-Frenkel model. The presence of adsorbed oxygen ions as trap-states at
      the grain boundary regions of the nanostructured thin film is considered to
      manifest this phenomenon. Under an applied field, the barrier of the trap
      potential is lowered and thermal emission of charge carriers takes place at
      different sample temperatures to induce nonlinearity in the current (I)-voltage
      (V) characteristics of the nanomaterial. Fitting of the Poole-Frenkel model with
      the I-V data shows that the nonlinearity is effective above 50 V under the
      operating conditions. Calculations of the energy of the trap level, acceptor
      level and Fermi level reveal the existence of deep level trap-states and a
      shallow acceptor level with acceptor concentration considerably higher than the
      trap-states. Hall measurements confirm the p-type semiconductivity of the film,
      with a hole concentration around 10(18) cm(-3). Thermopower measurements give a
      room-temperature Seebeck coefficient around 130 MUV K(-1). This temperature
      dependent conductivity enhancement within CuAlO2 nanomaterial may find
      interesting applications in transparent electronics and high-voltage applications
      for power supply networks.

PMID- 23535667
TI  - From strength to strength.

PMID- 23535665
TI  - Evaluation of generic medical information accessed via mobile phones at the point
      of care in resource-limited settings.
AB  - OBJECTIVE: Many mobile phone resources have been developed to increase access to
      health education in the developing world, yet few studies have compared these
      resources or quantified their performance in a resource-limited setting. This
      study aims to compare the performance of resident physicians in answering
      clinical scenarios using PubMed abstracts accessed via the PubMed for Handhelds
      (PubMed4Hh) website versus medical/drug reference applications (Medical Apps)
      accessed via software on the mobile phone. METHODS: A two-arm comparative study
      with crossover design was conducted. Subjects, who were resident physicians at
      the University of Botswana, completed eight scenarios, each with multi-part
      questions. The primary outcome was a grade for each question. The primary
      independent variable was the intervention arm and other independent variables
      included residency and question. RESULTS: Within each question type there were
      significant differences in 'percentage correct' between Medical Apps and
      PubMed4Hh for three of the six types of questions: drug-related,
      diagnosis/definitions, and treatment/management. Within each of these question
      types, Medical Apps had a higher percentage of fully correct responses than
      PubMed4Hh (63% vs 13%, 33% vs 12%, and 41% vs 13%, respectively). PubMed4Hh
      performed better for epidemiologic questions. CONCLUSIONS: While mobile access to
      primary literature remains important and serves an information niche, mobile
      applications with condensed content may be more appropriate for point-of-care
      information needs. Further research is required to examine the specific
      information needs of clinicians in resource-limited settings and to evaluate the
      appropriateness of current resources in bridging location- and context-specific
      information gaps.

PMID- 23535668
TI  - Prospective assessment of the Hong Kong Hospital Authority universal Down
      syndrome screening programme.
AB  - OBJECTIVE: To evaluate the performance of the locally developed universal Down
      syndrome screening programme. DESIGN: Population-based cohort study in the period
      July 2010 to June 2011 inclusive. SETTING: Four Hong Kong Hospital Authority
      Departments of Obstetrics and Gynaecology and a central university-based
      laboratory for maternal serum processing and risk determination. PARTICIPANTS:
      Women were offered either a first-trimester combined test (nuchal translucency,
      free beta human chorionic gonadotropin, and pregnancy-associated plasma protein
      A) or nuchal-translucency-only test, or a second-trimester double test (alpha
      fetoprotein and total human chorionic gonadotropin) for detection of Down
      syndrome according to their gestational age. Those with a trisomy 21 term risk of
      1:250 or higher were offered a diagnostic test. RESULTS: A total of 16 205
      pregnancies were screened of which 13 331 (82.3%) had a first-trimester combined
      test, 125 (0.8%) had a nuchal-translucency test only, and 2749 (17.0%) had a
      second-trimester double test. There were 38 pregnancies affected by Down
      syndrome. The first-trimester screening tests had a 91.2% (31/34) detection rate
      with a screen-positive rate of 5.1% (690/13 456). The second-trimester test had a
      100% (4/4) detection rate with a screen-positive rate of 6.3% (172/2749). There
      were seven (0.9%) pregnancies that miscarried following an invasive diagnostic
      test. There were two Down syndrome-affected live births, both with an estimated
      first-trimester trisomy 21 term risk lower than 1:250. CONCLUSION: The universal
      screening programme offered at the four units was effective and achieved the
      expected detection rates and low false-positive rates, and to maintain these, the
      current emphasis on training, quality control, and regular auditing must
      continue.

PMID- 23535669
TI  - Utility of infrared thermography for screening febrile subjects.
AB  - OBJECTIVE: To assess the utility of remote-sensing infrared thermography as a
      screening tool for fever. DESIGN: Cross-sectional study comparing body
      temperatures measured by remote-sensing infrared thermography (maximum for
      frontal, forehead, or lateral views) with core temperatures measured by aural or
      oral methods. SETTING: Accident and Emergency Department, Queen Mary Hospital,
      Hong Kong. PARTICIPANTS: A total of 1517 patients (747 men, 770 women) with or
      without fever; 34 of whom entered a substudy to measure the effects of distance
      on recorded temperature. MAIN OUTCOME MEASURES: The proportions of subjects with
      fever (core temperature of 38 degrees C or above) detected by remote-sensing
      infrared thermography compared with the proportion detected by conventional
      thermometry. RESULTS: The correlations between infrared thermography temperatures
      and core temperature were only moderate (r=0.36-0.44), albeit statistically
      significant. The temperature recorded by infrared thermography was inversely
      proportional to the distance from the camera. There were 113 (7.4%) subjects with
      a core temperature of 38 degrees C or above. The areas under the receiver
      operating characteristic curves for the three infrared thermography measurements
      were around 0.8. However, the maximum sensitivity achieved at a low cut-off
      temperature of 35 degrees C was only 0.87 (for frontal and lateral infrared
      thermography views), resulting in 13% of febrile subjects being missed. The
      maximum forehead temperature in general had the poorest performance among the
      three infrared thermography views. CONCLUSIONS: Forehead infrared thermography
      readings from a distance should be abandoned for fever screening. Although
      maximum lateral or frontal infrared thermography temperatures have reasonable
      correlations with core temperatures and areas under the receiver operating
      characteristic curves, the sensitivity-specificity combination might still not be
      high enough for screening febrile conditions, especially at border crossings with
      huge numbers of passengers.

PMID- 23535670
TI  - Multidisciplinary vascular malformations clinic in Hong Kong.
AB  - OBJECTIVE: To review clinical characteristics, imaging modalities, and treatment
      outcomes of patients referred to a multidisciplinary clinic for management of
      vascular malformations. DESIGN: Retrospective case series. SETTING:
      Multidisciplinary vascular malformation out-patient referral clinic in a teaching
      hospital in Hong Kong. PATIENTS: The 141 attendees of the clinic from August 2005
      to November 2011. MAIN OUTCOME MEASURES: Management and treatments offered, and
      responses to treatment. RESULTS: Of the 141 patients, 46% were diagnosed to have
      low-flow vascular malformations, 16% were diagnosed to have high-flow vascular
      malformations, and 15% were diagnosed to have a haemangioma. Prior to attending
      the clinic, approximately one third (32%) of the patients had a clinical
      diagnosis that was consistent with the final diagnosis. Overall, the radiological
      and clinical diagnoses were consistent in 43% of the patients. Magnetic resonance
      imaging and ultrasonography were the most commonly used imaging modalities. Of
      the 73 patients who received active treatment, 70% had a good response, 12% had
      minimal improvement, 8% had no change, and 7% had a recurrence or a major
      complication; in 3% of the patients the outcome was unknown. CONCLUSION: From
      this retrospective case series, it is evident that confusion still exists over
      vascular malformations and haemangiomas. Multidisciplinary clinics have a role in
      providing an accurate diagnosis and facilitating appropriate management and
      treatment plans. Magnetic resonance imaging and ultrasonography had demonstrable
      utility in determining the extent of the lesions and flow type.

PMID- 23535671
TI  - Early results of all-inside meniscal repairs using a pre-loaded suture anchor.
AB  - OBJECTIVES: To report the clinical and radiological results of all-inside
      meniscal repairs using a pre-loaded suture anchor. DESIGN: Case series. SETTING:
      Regional hospital, Hong Kong. PATIENTS: From January 2008 to June 2010, 51
      patients with a mean age of 26 (range, 15-48) years with 57 meniscal tears
      underwent meniscal repair utilising the all-inside meniscal repair technique
      entailing a pre-loaded suture anchor. All tears were located at red-red or red
      white zones. Concurrent anterior cruciate ligament reconstruction was performed
      in 37 (73%) of the patients. Patients were evaluated postoperatively based on the
      International Knee Documentation Committee score, clinical examination, and
      magnetic resonance imaging. Presence of locking, joint-line tenderness, effusion,
      and positive McMurray test were considered to indicate clinical failure. RESULTS:
      The mean follow-up was 19 (range, 12-39) months. An average of 2 (range, 1 to 4)
      suture devices was used per patient. The mean tear size was 20 (range, 10-40) mm.
      In all, 10 (18%) of the tears had failed clinically and 11 (19%) appeared
      unhealed on postoperative imaging. The mean International Knee Documentation
      Committee score improved significantly from 62 preoperatively to 81
      postoperatively (P<0.001). Patients with concurrent anterior cruciate ligament
      reconstruction had better corresponding scores postoperatively than
      preoperatively (mean, 83 vs 65, P<0.001). The clinical and radiological outcome
      was not related to the chronicity, location or length of the tear, or patient
      age. No postoperative extra- or intra-articular complications were encountered.
      CONCLUSION: All-inside meniscal repair using a pre-loaded suture anchor is safe
      and effective, and yielded an 83% clinical and 81% radiological success rate.

PMID- 23535672
TI  - Intracranial haemorrhage among Chinese children with immune thrombocytopenia in a
      Hong Kong regional hospital.
AB  - OBJECTIVE: To evaluate potential risk factors, presenting symptoms, management,
      and outcomes of intracranial haemorrhage in Chinese children with immune
      thrombocytopenia managed in a regional hospital. DESIGN: Retrospective case
      series. SETTING: A regional hospital in Hong Kong. PATIENTS: All paediatric
      patients with immune thrombocytopenia complicated by intracranial haemorrhage in
      the period January 1996 to December 2009. RESULTS: Nine episodes of intracranial
      haemorrhage were reported in eight patients (aged 0.9 to 19 years) with immune
      thrombocytopenia; three of the patients had acute immune thrombocytopenia and the
      other five had chronic immune thrombocytopenia. Intracranial haemorrhage occurred
      as early as the initial presentation with immune thrombocytopenia (n=2) and as
      late as up to 5 years after the diagnosis. The median platelet count at the time
      of intracranial haemorrhage was 12 x 10(9) /L (<10 x 10(9) /L [n=4]; 10-20 x
      10(9) /L [n=2]; >20 x 10(9) /L [n=3]). The bleeding was considered spontaneous in
      six episodes, while head trauma (n=2) and vascular malformation (n=1) were
      identified in three patients with mild-to-moderate thrombocytopenia (42-82 x
      10(9) /L) at the time of the bleed. Headache and mucosal bleeding were the
      commonest presenting symptoms (n=5). All patients received multimodal treatment
      after diagnosis of intracranial haemorrhage, and included platelet transfusion
      (n=8), intravenous immunoglobulin (n=6), methylprednisolone (n=4), and
      splenectomy (n=4); three individuals underwent neurosurgical interventions. One
      (11%) patient died of posterior fossa bleeding and one (11%) had neurological
      sequelae. All survivors achieved remission of their immune thrombocytopenia with
      a median follow-up of 5.3 years. CONCLUSION: Intracranial haemorrhage can occur
      anytime during the course of immune thrombocytopenia. A high index of suspicion
      for intracranial haemorrhage should be maintained during follow-up, as favourable
      outcomes can be achieved after early and vigorous interventions.

PMID- 23535673
TI  - Intra-arterial revascularisation therapy for acute ischaemic stroke: initial
      experience in a Hong Kong hospital.
AB  - OBJECTIVES: To assess the outcome of acute ischaemic stroke patients who received
      intra-arterial therapy in our unit. DESIGN: Case series. SETTING: A tertiary
      hospital in Hong Kong. PATIENTS: Patients with ischaemic stroke due to large
      artery occlusion treated within 6 hours from symptom onset between January 2007
      and May 2011. INTERVENTION: Acute intra-arterial revascularisation therapy. MAIN
      OUTCOME MEASURES: Primary outcome was functional independence (modified Rankin
      Scale score of <= 2) at 3 months. Secondary outcome was rate of recanalisation.
      Safety outcomes were symptomatic intracranial haemorrhage and 3-month mortality.
      RESULTS: Twenty-one patients with a mean age of 67 years fulfilled the inclusion
      criteria. Their mean National Institutes of Health Stroke Scale score was 18. The
      mean onset-to-puncture time was 212 minutes. Nine received intra-arterial tissue
      plasminogen activator alone, 11 had an adjunctive mechanical thrombectomy, and
      one received balloon angioplasty without tissue plasminogen activator. At the end
      of the procedure, thrombolysis grade 2a or better was attained in 18 (86%) of the
      patients, and 8 (38%) achieved functional independence at 3 months. Rates of
      symptomatic intracranial haemorrhage and 3-month mortality were 10% and 24%,
      respectively. CONCLUSION: In this setting, intra-arterial revascularisation
      therapy appeared safe and efficacious for this selected group of ischaemic stroke
      patients with large artery occlusions. Experience gained from this pilot study
      may help improve clinical outcomes of such patients.

PMID- 23535674
TI  - Percutaneous nephrostomy, nephrolithotomy and combined ureteroscopic lithotripsy
      using the supine approach.
AB  - OBJECTIVES: (1) To evaluate the safety and efficacy of supine percutaneous
      nephrostomy, nephrolithotomy, and combined percutaneous nephrolithotomy and
      ureteroscopic lithotripsy. (2) To describe the skill-acquiring process in supine
      procedures and share our initial experience. DESIGN: Three-staged case series
      with prospective data collection. SETTING: Two public hospitals in Hong Kong.
      PATIENTS AND INTERVENTION: Stage 1: Forty patients indicated for percutaneous
      renal access were recruited for supine percutaneous nephrostomy with prospective
      data collection. Stage 2: A prospective comparative study of percutaneous
      nephrolithotomy involving 60 patients allocated non-randomly to a supine (n=25)
      or prone (n=35) approach was conducted. Stage 3: Data of 11 patients who
      underwent simultaneous supine percutaneous nephrolithotomy and ureteroscopic
      lithotripsy were prospectively captured. RESULTS: Stage 1: The procedural success
      rate was 100%. The mean operating time in unilateral procedures was 44 minutes;
      one patient had perinephric haematoma as a complication. Stage 2: Overall stone
      free rates for prone and supine procedures were 46% and 68%, respectively
      (P=0.087), and mean operating times were 122 and 123 minutes, respectively
      (P=0.905). Stage 3: Of the 11 patients, six were rendered stone-free after the
      first combined procedure, and one experienced transient postoperative fever.
      There was no major complication. CONCLUSION: Percutaneous nephrolithotomy was
      feasible via both prone and supine approaches. With the exception of staghorn
      stones, the supine percutaneous approach was an equally safe and effective option
      for patients with specific conditions favouring such an approach. The ability to
      incorporate simultaneous ureteroscopic lithotripsy was an additional benefit of
      adopting the supine approach.

PMID- 23535676
TI  - Workshop 11-sources of bias in studies of systematic reviews with or without meta
      analysis.

PMID- 23535675
TI  - Eyelid tumours and pseudotumours in Hong Kong: a ten-year experience.
AB  - OBJECTIVE: To describe the clinicopathological characteristics of patients with
      eyelid tumours in Hong Kong. DESIGN: Retrospective case series. SETTING: A
      tertiary eye centre in Hong Kong. PATIENTS: A computerised retrieval system was
      used to identify all patients who underwent eyelid mass excisions with
      histological reports, encountered in the period 2000 to 2009, in a tertiary eye
      centre. The demographics (age, gender), clinical features (laterality, tumour
      topography), and the pathological diagnosis of each patient were documented.
      Descriptive statistical tabulation and analyses were performed on the data.
      RESULTS: In all, 198 patients were identified; all were Chinese. Their mean age
      was 54 years for benign lesions and 68 years for malignant ones. Women were more
      commonly affected. Benign tumourous lesions occurred more commonly on the upper
      (n=91; 54%) than lower eyelid (n=79; 47%), whereas malignant lesions more often
      affected the lower (n=17, 61%) than upper (n=11, 39%) eyelid. The distribution of
      left and right eye involvement was similar (103 vs 101, respectively). In six
      patients, there were bilateral benign lesion. Regarding benign masses, 45 (27%)
      were intradermal neavi, 38 (22%) were squamous papillomas, 25 (15%) were
      seborrhoeic keratosis lesions, 14 (8%) were epidermoid cysts, and 7 (4%) were
      compound naevi. Regarding malignant eyelid tumours, the most common was basal
      cell carcinomas (n=12, 43%), 5 (18%) were squamous cell carcinomas, 3 (11%) were
      actinic keratosis lesions, and 2 (7%) each were sebaceous gland carcinomas and
      melanomas. CONCLUSION: Benign lesions constituted the majority of these eyelid
      tumours. Among the malignant lesions, basal cell carcinoma was the commonest
      type, with lower lid involvement in majority. Sebaceous gland carcinoma is not
      rare, which is in contrast to Caucasian populations. The relative frequencies of
      the most common malignant tumours in Hong Kong differed substantially from those
      reported in other Asian studies.

PMID- 23535677
TI  - Brugada syndrome.
AB  - As a clinical entity the Brugada syndrome has existed since 1992 and has been
      associated with a high risk of sudden cardiac death predominately in younger
      males. Patients can present with symptoms (ie syncope, palpitations, aborted
      sudden cardiac death) and asymptomatically. Its three characteristic
      electrocardiographic patterns can occur both spontaneously or after provocation
      with sodium channel-blocking agents. Risk stratification and the need for
      treatment depend on the patient's symptoms, electrocardiography, family history,
      and electrophysiological inducibility to discern if treatment by implantable
      cardioverter defibrillator, the only effective treatment to date, is appropriate.
      This review focuses on Brugada syndrome and various aspects of the disease
      including proposed mechanisms, epidemiology, clinical presentations, genetics,
      diagnosis, risk stratification, and treatment options.

PMID- 23535679
TI  - Degos' syndrome complicated by bowel perforation: focus on radiological findings.
AB  - We describe a 50-year-old man who first presented with multiple skin lesions
      which were characteristic of Degos' syndrome. The patient developed multiple
      episodes of abdominal pain. Some episodes resolved with conservative management,
      for others he underwent urgent operations for bowel perforations. The patient
      subsequently underwent extensive small bowel resection, but further systemic
      deterioration ensued and he died. The imaging findings of Degos' syndrome and the
      implications of pneumatosis intestinalis and pneumoperitoneum are discussed.

PMID- 23535678
TI  - Cytogenetic biodosimetry: what it is and how we do it.
AB  - Dicentric assay is the international gold standard for cytogenetic biodosimetry
      after radiation exposure, despite being very labour-intensive, time-consuming,
      and highly expertise-dependent. It involves the identification of centromeres and
      structure of solid-stained chromosomes and the enumeration of dicentric
      chromosomes in a large number of first-division metaphases of cultured T
      lymphocytes. The dicentric yield is used to estimate the radiation exposure
      dosage according to a statistically derived and predetermined dose-response
      curve. It can be used for population triage after large-scale accidental over
      exposure to ionising radiation or with a view to making clinical decisions for
      individual patients receiving substantial radiation. In this report, we describe
      our experience in the establishment of a cytogenetic biodosimetry laboratory in
      Queen Elizabeth Hospital, Hong Kong. This was part of the contingency plan for
      emergency measures against radiation accidents at nuclear power stations.

PMID- 23535680
TI  - Vascular calcification in a young patient with end-stage renal disease.
AB  - Vascular calcification in children with long-standing dialysis is a unique
      phenomenon. Hyperphosphataemia and hyperparathyroidism are the major pathogenic
      risk factors. We describe a young patient with end-stage renal disease diagnosed
      since childhood and underwent prolonged dialysis therapy. He was admitted for
      recurrent episodes of acute joint pain. Investigations confirmed diffuse
      periarticular, vascular, and intracardiac calcifications which were rarely seen
      in the young population. He underwent parathyroidectomy and incidentally found to
      have a co-existing papillary carcinoma of thyroid. After parathyroidectomy,
      serial X-rays showed resorption of these calcifications.

PMID- 23535681
TI  - Congenital fibrosis of extraocular muscle type 1A due to KIF21A mutation: first
      case report from Hong Kong.
AB  - With the advancement of ophthalmological genetics, the molecular basis for more
      and more eye diseases can be elucidated. Congenital fibrosis of extraocular
      muscle (CFEOM) is an example. It is characterised by a congenital non-progressive
      restrictive ophthalmoplegia and ptosis. It is an autosomal dominant disease,
      caused by mutations of the KIF21A gene. With positive family history and typical
      ophthalmological findings, mutational analysis of KIF21A gene should be
      performed, not only to confirming the diagnosis, but also to offer a prognosis,
      for genetic counselling, and the possibility of prenatal diagnosis. Here we
      report the first KIF21A mutation associated with CFEOM1A in Hong Kong.

PMID- 23535682
TI  - Nasopharyngeal encephalocele: a rare cause of upper airway obstruction.
AB  - Nasopharyngeal encephalocele is a rare, benign congenital anomaly. It has the
      potential to be fatal due to airway obstruction. Here, we report on a 34-day-old
      infant with pneumonia who underwent mechanical ventilation. An upper airway
      evaluation was performed due to prolonged intubation, and revealed the presence
      of a nasopharyngeal encephalocele. The patient tolerated extubation and oral
      feeding after surgical resection of the lesion. Awareness of the condition can
      help clinicians arrive at an earlier diagnosis and enhance management.

PMID- 23535683
TI  - Use of insulin in primary care.

PMID- 23535684
TI  - Authors' reply.

PMID- 23535685
TI  - A neonate with generalised bullae and pyloric atresia.

PMID- 23535686
TI  - Cervical subcutaneous emphysema and pneumomediastinum after sneezing.

PMID- 23535687
TI  - Increase in reported coccidioidomycosis--United States, 1998-2011.
AB  - Coccidioidomycosis, also known as valley fever, is an infection caused by
      inhalation of Coccidioides spp. spores. This soil-dwelling fungus is endemic to
      arid regions of Mexico, Central and South America, and the southwestern United
      States. Symptomatic patients typically experience a self-limited influenza-like
      illness, but some develop severe or chronic pulmonary disease, and less than 1%
      of patients experience disseminated disease. Coccidioidomycosis can be costly and
      debilitating, with nearly 75% of patients missing work or school because of their
      illness, and more than 40% requiring hospitalization. Previous publications have
      reported state-specific increases in coccidioidomycosis in Arizona and California
      during 1998-2001 and 2000-2007, respectively. To characterize long-term national
      trends, CDC analyzed data from the National Notifiable Diseases Surveillance
      System (NNDSS) for the period 1998-2011. This report describes the results of
      that analysis, which indicated that the incidence of reported coccidioidomycosis
      increased substantially during this period, from 5.3 per 100,000 population in
      the endemic area (Arizona, California, Nevada, New Mexico, and Utah) in 1998 to
      42.6 per 100,000 in 2011. Health-care providers should be aware of this
      increasingly common infection when treating persons with influenza-like illness
      or pneumonia who live in or have traveled to endemic areas.

PMID- 23535688
TI  - Two measles outbreaks after importation--Utah, March-June 2011.
AB  - Before licensure of a measles vaccine in 1963, more than 500,000 measles cases on
      average were reported in the United States each year during 1951-1962. By 1993,
      through measles vaccination and control efforts, only 312 cases were reported
      nationwide. In 2000, the last year in which an outbreak had occurred in Utah,
      measles was declared "not endemic in the United States," but measles importations
      continue to occur, leading to outbreaks, especially among unvaccinated persons.
      Many U.S. health-care personnel have never seen a measles patient, which might
      hamper diagnosis and delay reporting. During March-June 2011, local health
      departments collaborated with the state health department in Utah to investigate
      two measles outbreaks comprising 13 confirmed cases. The first outbreak, with
      seven confirmed cases, was associated with an unvaccinated U.S. resident who
      traveled internationally; the second, with six confirmed cases, had an
      undetermined source. The genotype D4 sequences obtained from these two outbreaks
      differed by a single nucleotide, suggesting two separate importations. Health
      care providers should remind their patients of the importance of being current
      with measles, mumps, and rubella (MMR) vaccination; this is especially important
      before international travel. Measles should be considered in the differential
      diagnosis of febrile rash illness, especially in unvaccinated persons with recent
      international travel. Reporting a confirmed or suspected case immediately to
      public health authorities is critical to limit the spread of measles.

PMID- 23535689
TI  - Three cases of congenital rubella syndrome in the postelimination era--Maryland,
      Alabama, and Illinois, 2012.
AB  - Infection with rubella virus during pregnancy, especially during the first
      trimester, can result in congenital rubella syndrome (CRS). Serious
      manifestations of CRS include deafness, cataracts, cardiac defects, mental
      retardation, and death. In the last major rubella epidemic in the United States,
      during 1964-1965, an estimated 12.5 million rubella virus infections resulted in
      11,250 therapeutic or spontaneous abortions, 2,100 neonatal deaths, and 20,000
      infants born with CRS. In 2004, after implementation of a universal vaccination
      program, elimination of endemic rubella virus transmission was documented in the
      United States; evidence also suggests that endemic rubella has been eliminated in
      the entire World Health Organization (WHO) Region of the Americas. However,
      rubella virus continues to circulate elsewhere in the world, especially in
      regions where rubella vaccination programs have not been established (e.g., the
      African Region), placing the United States at risk for imported cases of rubella
      and CRS. During 2004-2012, 79 cases of rubella and six cases of CRS were reported
      in the United States; all of the cases were import-associated or from unknown
      sources. Of the three cases of CRS that occurred in 2012, conditions included
      cardiac defects, cataracts, hearing impairment, and pericardial effusion in one
      infant; patent ductus arteriosus, cardiomegaly, thrombocytopenia, and pneumonitis
      in a second infant; and cataracts, thrombocytopenia, and cardiac defects in a
      third infant. All three mothers had been in Africa early in their pregnancies.
      While rubella remains endemic elsewhere in the world, imported CRS will continue
      to be a public health concern in the United States.

PMID- 23535690
TI  - Notes from the field: Outbreak of severe respiratory illness in an assisted
      living facility--Colorado, 2012.
AB  - On May 28, 2012, the Colorado Department of Public Health and Environment (CDPHE)
      was notified of six cases of severe respiratory illness among 12 residents of an
      assisted-living facility (ALF) specializing in the care of elderly persons with
      dementia or memory loss. During May 22-27, 2012, five residents were
      hospitalized, and two developed invasive disease with Streptococcus pneumoniae
      (pneumococcal) bacteremia. S. pneumoniae is spread by airborne droplets and
      causes an estimated 175,000 hospitalizations and 50,000 cases of pneumococcal
      bacteremia each year. The case-fatality rate of pneumococcal bacteremia can be as
      high as 60% among the elderly.

PMID- 23535691
TI  - Functional assembly of a multi-enzyme methanol oxidation cascade on a surface
      displayed trifunctional scaffold for enhanced NADH production.
AB  - We report a simple and low-cost strategy that allows the sequential and site
      specific assembly of a dehydrogenase-based multi-enzyme cascade for methanol
      oxidation on the yeast surface using the high-affinity interactions between three
      orthogonal cohesin-dockerin pairs. The multi-enzyme cascade showed 5 times higher
      NADH production rate than the non-complexed enzyme mixture, a result of efficient
      substrate channeling.

PMID- 23535696
TI  - A regioselective synthesis of 1-haloisoquinolines via ruthenium-catalyzed
      cyclization of O-methylbenzohydroximoyl halides with alkynes.
AB  - A ruthenium-catalyzed highly regioselective cyclization of substituted N-methoxy
      benzimidoyl halides with alkynes in the presence of CsOAc (25 mol%) to give
      substituted 1-halo and 1-alkoxy substituted isoquinolines in good to excellent
      yields is described.

PMID- 23535697
TI  - Predicting submicron air pollution indicators: a machine learning approach.
AB  - The regulation of air pollutant levels is rapidly becoming one of the most
      important tasks for the governments of developing countries, especially China.
      Submicron particles, such as ultrafine particles (UFP, aerodynamic diameter <=
      100 nm) and particulate matter <= 1.0 micrometers (PM1.0), are an unregulated
      emerging health threat to humans, but the relationships between the concentration
      of these particles and meteorological and traffic factors are poorly understood.
      To shed some light on these connections, we employed a range of machine learning
      techniques to predict UFP and PM1.0 levels based on a dataset consisting of
      observations of weather and traffic variables recorded at a busy roadside in
      Hangzhou, China. Based upon the thorough examination of over twenty five
      classifiers used for this task, we find that it is possible to predict PM1.0 and
      UFP levels reasonably accurately and that tree-based classification models
      (Alternating Decision Tree and Random Forests) perform the best for both these
      particles. In addition, weather variables show a stronger relationship with PM1.0
      and UFP levels, and thus cannot be ignored for predicting submicron particle
      levels. Overall, this study has demonstrated the potential application value of
      systematically collecting and analysing datasets using machine learning
      techniques for the prediction of submicron sized ambient air pollutants.

PMID- 23535698
TI  - Spontaneous synchronized tapping to an auditory rhythm in a chimpanzee.
AB  - Humans actively use behavioral synchrony such as dancing and singing when they
      intend to make affiliative relationships. Such advanced synchronous movement
      occurs even unconsciously when we hear rhythmically complex music. A foundation
      for this tendency may be an evolutionary adaptation for group living but
      evolutionary origins of human synchronous activity is unclear. Here we show the
      first evidence that a member of our closest living relatives, a chimpanzee,
      spontaneously synchronizes her movement with an auditory rhythm: After a training
      to tap illuminated keys on an electric keyboard, one chimpanzee spontaneously
      aligned her tapping with the sound when she heard an isochronous distractor
      sound. This result indicates that sensitivity to, and tendency toward synchronous
      movement with an auditory rhythm exist in chimpanzees, although humans may have
      expanded it to unique forms of auditory and visual communication during the
      course of human evolution.

PMID- 23535699
TI  - Impact of isoniazid preventive therapy on mortality among children less than 5
      years old following exposure to tuberculosis at home in Guinea-Bissau: a
      prospective cohort study.
AB  - OBJECTIVE: In a cohort of children less than 5 years old exposed to adult
      intrathoracic tuberculosis (TB) in 1996-1998, we found 66% increased mortality
      compared with community controls. In 2005, we implemented isoniazid preventive
      therapy (IPT) for children exposed to TB at home, and the present study evaluates
      the effect of this intervention on mortality. SETTING: This prospective cohort
      study was conducted in six suburban areas included in the demographic
      surveillance system of the Bandim Health Project in Bissau, the capital city of
      Guinea-Bissau. PARTICIPANTS: All children less than 5 years of age and living in
      the same house as an adult with intrathoracic TB registered for treatment in the
      study area between 2005 and 2007 were evaluated for inclusion in the IPT
      programme. MAIN OUTCOME MEASURES (END POINTS): The all-cause mortality rate ratio
      (MRR) between exposed children on IPT, exposed without IPT and unexposed
      community control children. RESULTS: A total of 1396 children were identified as
      living in the same houses as 416 adult TB cases; of those, 691 were enrolled in
      the IPT programme. Compared with community controls, the IPT children had an MRR
      of 0.30 (95%CI 0.1 to 1.2). The MRR comparing exposed children with and without
      IPT was 0.21 (0.0 to 1.1). The relative mortality in IPT children compared with
      community controls in 2005-2008 differed significantly from the relative
      mortality of exposed untreated children compared with the community controls in
      1996-1998 (test of interaction, p=0.01). CONCLUSIONS: In 2005-2008, exposed
      children on IPT had 70% lower mortality than the community control children,
      though not significantly. Relative to the community control children, the
      mortality among TB-exposed children on IPT in 2005-2008 was significantly lower
      than the mortality among TB-exposed children not on IPT in 1996-1998.

PMID- 23535700
TI  - Intravenous nicardipine and labetalol use in hypertensive patients with signs or
      symptoms suggestive of end-organ damage in the emergency department: a subgroup
      analysis of the CLUE trial.
AB  - OBJECTIVE: To compare the efficacy of Food and Drug Administration recommended
      dosing of nicardipine versus labetalol for the management of hypertensive
      patients with signs and/or symptoms (S/S) suggestive of end-organ damage (EOD).
      DESIGN: Secondary analysis of the multicentre prospective, randomised CLUE trial.
      SETTING: 13 academic emergency departments in the USA. PARTICIPANTS: Eligible
      patients had two systolic blood pressure (SBP) measures >=180 mm Hg at least 10
      min apart, no contraindications to nicardipine or labetalol and predefined S/S
      suggestive of EOD on arrival. INTERVENTIONS: Medications were administered by
      continuous infusion (nicardipine) or repeat intravenous bolus (labetalol) for a
      study period of 30 min or until a specified target SBP +/-20 mm Hg was achieved.
      PRIMARY OUTCOME MEASURE: Percentage of participants achieving a predefined target
      SBP range (TR) defined as an SBP within +/-20 mm Hg as established by the
      treating physician. RESULTS: Of the 141 eligible patients, 49.6% received
      nicardipine, 51.7% were women and 81.6% were black. Mean age was 52.2+/-13.9
      years. Median initial SBP did not differ in the nicardipine (210.5 (IQR 197-226)
      mm Hg) and labetalol (210 (200-226) mm Hg) groups (p=0.862). Nicardipine patients
      were more likely to have a history of diabetes (41.4% vs 25.7%, p=0.05) but there
      were no other historical, demographic or laboratory differences between groups.
      Within 30 min, nicardipine patients more often reached the target SBP range than
      those receiving labetalol (91.4% vs 76.1%, difference=15.3% (95% CI 3.5% to
      27.3%); p=0.01). On multivariable modelling with adjustment for gender and
      clinical site, nicardipine patients were more likely to be in TR by 30 min than
      patients receiving labetalol (OR 3.65, 95% CI 1.31 to 10.18, C statistic=0.72).
      CONCLUSIONS: In the setting of hypertension with suspected EOD, patients treated
      with nicardipine are more likely to reach prespecified SBP targets within 30 min
      than patients receiving labetalol. CLINICAL TRIAL REGISTRATION: NCT00765648,
      clinicaltrials.gov.

PMID- 23535701
TI  - Pandemic influenza in Papua New Guinea: a modelling study comparison with
      pandemic spread in a developed country.
AB  - OBJECTIVES: The possible occurrence of a highly pathogenic influenza strain is of
      concern to health authorities worldwide. It is known that during past influenza
      pandemics developing countries have experienced considerably higher death rates
      compared with developed countries. Furthermore, many developing countries lack
      appropriate pandemic preparedness plans. Mathematical modelling studies to guide
      the development of such plans are largely focused on predicting pandemic
      influenza spread in developed nations. However, intervention strategies shown by
      modelling studies to be highly effective for developed countries give limited
      guidance as to the impact which an influenza pandemic may have on low-income
      countries given different demographics and resource constraints. To address this,
      an individual-based model of a Papua New Guinean (PNG) community was created and
      used to simulate the spread of a novel influenza strain. The results were
      compared with those obtained from a comparable Australian model. DESIGN: A
      modelling study. SETTING: The towns of Madang in PNG (population ~35 000) and
      Albany (population ~30 000) in Australia. OUTCOME MEASURES: Daily and cumulative
      illness attack rates in both models following introduction of a novel influenza
      strain into a naive population, for an unmitigated scenario and two social
      distancing intervention scenarios. RESULTS: The unmitigated scenario indicated an
      approximately 50% higher attack rate in PNG compared with the Australian model.
      The two social distancing-based interventions strategies were 60-70% less
      effective in a PNG setting compared with an Australian setting. CONCLUSIONS: This
      study provides further evidence that an influenza pandemic occurring in a low
      income country such as PNG may have a greater impact than one occurring in a
      developed country, and that PNG-feasible interventions may be substantially less
      effective. The larger average household size in PNG, the larger proportion of the
      population under 18 and greater community-wide contact all contribute to this
      feature.

PMID- 23535702
TI  - Correction.

PMID- 23535703
TI  - Study protocol for a randomised controlled double-blinded trial of the dose
      dependent efficacy and safety of primaquine for clearance of gametocytes in
      children with uncomplicated falciparum malaria in Uganda.
AB  - OBJECTIVES: For the purpose of blocking transmission of Plasmodium falciparum
      malaria from humans to mosquitoes, a single dose of primaquine is recommended by
      the WHO as an addition to artemisinin combination therapy. Primaquine clears
      gametocytes but causes dose-dependent haemolysis in individuals with glucose-6
      phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the
      optimal dosing of primaquine for malaria elimination programmes and for the
      purpose of interrupting the spread of artemisinin-resistant malaria. This study
      investigates the efficacy and safety of reducing doses of primaquine for
      clearance of gametocytes in participants with normal G6PD status. METHODS AND
      ANALYSIS: In this prospective, four-armed randomised placebo-controlled double
      blinded trial, children aged 1-10 years, weighing over 10 kg, with haemoglobin
      >=8 g/dl and uncomplicated P falciparum malaria are treated with artemether
      lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg
      base/kg) or placebo on the third day of treatment. Participants are followed up
      for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence
      based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the
      number of days to gametocyte clearance in each treatment arm and secondarily the
      area under the curve of gametocyte density over time. Analysis is for non
      inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety
      is assessed by pair-wise comparisons of the arithmetic mean (+/-SD) change in
      haemoglobin concentration per treatment arm and analysed for superiority to
      placebo and incidence of adverse events. Ethics and dissemination Approval was
      obtained from the ethical committees of Makerere University School of Medicine,
      the Ugandan National Council of Science and Technology and the London School of
      Hygiene and Tropical Medicine. RESULTS: These will be disseminated to inform
      malaria elimination policy, through peer-reviewed publication and academic
      presentations.

PMID- 23535704
TI  - Comparison of select Advanced Clinical Solutions embedded Effort measures to the
      Word Memory Test in the detection of suboptimal effort.
AB  - This brief report sought to evaluate the classification statistics of the
      Advanced Clinical Solutions (ACS) embedded measures of symptom validity in
      relation to the Word Memory Test (WMT), a well-established standalone measure of
      effort in a sample of active duty military service members with a history of mild
      traumatic brain injury. Results demonstrated that relative to the WMT, the ACS
      embedded measures had adequate specificity, but lacked sensitivity. This result
      is in agreement with previous studies demonstrating poor sensitivity for embedded
      effort measures relative to standalone Symptom Validity Tests.

PMID- 23535705
TI  - Development of a (11)C-labeled tetrazine for rapid tetrazine-trans-cyclooctene
      ligation.
AB  - Tetrazine-trans-cyclooctene ligations are remarkably fast and selective reactions
      even at low micro-molar concentrations. In bioorthogonal radiochemistry, tools
      that enable conjugation of radioactive probes to pre-targeted vectors are of
      great interest. Herein, we describe the successful development of the first (11)C
      labelled tetrazine and its reaction with trans-cyclooctenol.

PMID- 23535707
TI  - Three cases of stroke following peripheral venous interventions.

PMID- 23535706
TI  - On the role of four small hairpins in the HIV-1 RNA genome.
AB  - An RNA secondary structure model for the complete HIV-1 genome has recently been
      published based on SHAPE technology. Several well-known RNA motifs such as TAR
      and RRE were confirmed and numerous new structured motifs were described that may
      play important roles in virus replication. The 9 kb viral RNA genome is densely
      packed with many RNA hairpin motifs and the collective fold may play an important
      role in HIV-1 biology. We initially focused on 16 RNA hairpin motifs scattered
      along the viral genome. We considered conservation of these structures, despite
      sequence variation among virus isolates, as a first indication for a significant
      function. Four relatively small hairpins exhibited considerable structural
      conservation and were selected for experimental validation in virus replication
      assays. Mutations were introduced into the HIV-1 RNA genome to destabilize
      individual RNA structures without affecting the protein-coding properties (silent
      codon changes). No major virus replication defects were scored, suggesting that
      these four hairpin structures do not play essential roles in HIV-1 replication.

PMID- 23535708
TI  - Risk factors for multiple malignancies in the head and neck.
AB  - OBJECTIVE: To define the prognostic role of multiple epidemiological, clinical,
      and biological factors for the development of multiple malignancies (MM) in
      patients with head and neck cancer (HNC). STUDY DESIGN: Historical cohort study.
      p53 gene status, microsatellite instability (MSI) of the index tumor, and
      inherited chromosome fragility (CF) were studied. SETTING: Ninety-six consecutive
      patients affected by primary HNC, between January 1987 and October 1991, who were
      eligible for curative radiation therapy were followed up. SUBJECTS AND METHODS:
      p53 gene status, MSI, and CF in 96 curative radiotherapy-treated patients were
      correlated with the risk for MM. RESULTS: Multiple malignancies occurred in
      28.9%. Microsatellite instability (P = 0.05), CF (P < 0.01), and smoking after
      treatment of the index tumor (P = 0.02) were correlated with an increased risk of
      MM. CONCLUSION: Genetic susceptibility may play a central role for MM development
      in patients with HNC.

PMID- 23535709
TI  - Considerations for initial dosing of botulinum toxin in treatment of adductor
      spasmodic dysphonia.
AB  - OBJECTIVES: To assess the effect on voice improvement and duration of breathiness
      based on initial dose of onabotulinum toxin A (BTX-A) in the management of
      adductor spasmodic dysphonia (SD) and to compare voice outcomes for initial
      bilaterally injected doses of 1.25 units (group A) vs 2.5 units (group B) of BTX
      A. STUDY DESIGN: Case series with chart review of patients with adductor SD
      treated at a tertiary care facility from 1990 to 2011. SETTING: Academic
      subspecialty laryngology practice. METHODS: Demographic data (age and sex), voice
      rating, duration of voice improvement, and breathiness were evaluated and
      compared between groups A and B using the Student t test and chi(2) analysis.
      RESULTS: Of 478 patients identified, 305 (223 in group A, 82 in group B) patients
      met inclusion criteria. The average age was 56.2 years in group A and 57.4 years
      in group B (P = .5). The female to male ratio was 2.91 for group A vs 3.56 for
      group B (P = .61). Good voice outcomes (grade 3 or 4) were reported by 91% of
      group A patients vs 94% of group B (P = .75). The average duration of voice
      improvement was 99.7 days for group A and 108.3 days for group B (P = .54). The
      average duration of breathiness was 10.88 days for group A vs 15.42 days for
      group B (P = .02). CONCLUSION: Patients injected with 1.25 units bilaterally had
      a statistically significant shorter duration of breathiness without a
      statistically significant difference in clinical effectiveness or voice outcome.
      It is therefore recommended that a relatively low initial BTX-A dose be used with
      subsequent titration to achieve improved voice outcomes.

PMID- 23535710
TI  - Workplace injuries in Fiji: a population-based study (TRIP 7).
AB  - BACKGROUND: Workplace injury rates in low and middle-income countries are known
      to be high. Contemporary data on this topic from Pacific Island countries and
      territories are scant. AIMS: To describe the epidemiology of fatal and
      hospitalized workplace injuries in Fiji using a population-based trauma registry.
      METHODS: An analysis of data from a prospective population-based surveillance
      registry investigated the characteristics associated with workplace injuries
      resulting in death or hospital admission among people aged 15 years and older in
      Viti Levu, the largest island in the Republic of Fiji, from October 2005 to
      September 2006. Incidence rates were calculated using denominator data from the
      2004-05 Fiji Employment Survey. RESULTS: One hundred and eighty-nine individuals
      met the study eligibility criteria (including nine deaths). This corresponded to
      annual injury-related hospitalization and death rates of 73.4 and 3.7 per
      100&emsp14;000 workers, respectively. Males accounted for 95% of injuries, and
      hospitalization rates were highest among those aged 15-29 years (33 per
      100&emsp14;000 workers). Fijian and Indian workers had similar rates of admission
      to hospital (38.3 and 31.8 per 100&emsp14;000 workers, respectively). Fractures
      (40%) and 'cuts/bites/open wounds' (32%) were the commonest types of injury while
      'being hit by a person or object' (34%), falls (27%) and 'cutting or piercing'
      injuries (27%) were the commonest mechanisms. Overall, 7% of injuries were deemed
      intentional. CONCLUSIONS: Acknowledging the likely underestimation of the overall
      burden of workplace injuries, these findings support the need to identify context
      specific risk factors and effective approaches to preventing workplace injuries
      in Fiji.

PMID- 23535711
TI  - Occupational allergy to squid (Loligo vulgaris).
AB  - Occupational allergy from exposure to squid has been rarely described, mainly as
      contact dermatitis or urticaria. Our report presents the first case of
      occupational asthma, rhinitis, conjunctivitis and contact urticaria to squid in a
      33-year-old seafood production worker, with documented increased eosinophilia in
      the nasal and tear fluids after specific inhalation challenge test (SICT) with
      squid. IgE-mediated sensitization to squid was confirmed by positive skin prick
      test and opened skin test with squid extract. SICT demonstrated a direct and
      significant link between the exposure to squid and the allergic response from the
      respiratory system and conjunctiva.

PMID- 23535712
TI  - Navigating multiple options and social relationships in plural health systems: a
      qualitative study exploring healthcare seeking for sick children in Sierra Leone.
AB  - BACKGROUND: Sierra Leone has emerged from civil war but remains in the lowest
      tier of the human development index. While significant health reforms, such as
      the removal of user fees, aim to increase access to services, little is known
      about how families navigate a plural health system in seeking health care for
      sick children. This research aims to build on recent care-seeking literature that
      emphasizes a shift from static supply-and-demand paradigms towards more nuanced
      understandings, which account for the role of household agency and social support
      in navigating a landscape of options. METHODS: A rapid ethnographic assessment
      was conducted in villages near and far from facilities across four districts:
      Kambia, Kailahun, Pujehun and Tonkolili. In total, 36 focus group discussions and
      64 in-depth interviews were completed in 12 villages. Structured observation in
      each village detailed sources of health care. RESULTS: When a child becomes sick,
      households work within their geographic, social and financial context to seek
      care from sources including home treatment, herbalists, religious healers, drug
      peddlers and facility-based providers. Pathways vary, but respondents living
      closer to facilities emphasized facility care compared with those living further
      away, who take multi-pronged approaches. Beyond factors linked to the location
      and type of healthcare provision, social networks and collaboration within and
      across families determine how best to care for a sick child and can contribute to
      (or hinder) the mobilization of resources necessary to access care. Husbands play
      a particularly critical role in mobilizing funds and facilitating transport to
      facilities. CONCLUSION: Caregivers in Sierra Leone have endured in the absence of
      adequate health care for decades: their resourcefulness in devising multiple
      strategies for care must be recognized and integrated into the service delivery
      reforms that are making health care increasingly available.

PMID- 23535713
TI  - Brazil's engagement in health co-operation: what can it contribute to the global
      health debate?

PMID- 23535715
TI  - Multi-sensor fusion with interacting multiple model filter for improved aircraft
      position accuracy.
AB  - The International Civil Aviation Organization (ICAO) has decided to adopt
      Communications, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) as
      the 21st century standard for navigation. Accordingly, ICAO members have provided
      an impetus to develop related technology and build sufficient infrastructure. For
      aviation surveillance with CNS/ATM, Ground-Based Augmentation System (GBAS),
      Automatic Dependent Surveillance-Broadcast (ADS-B), multilateration (MLAT) and
      wide-area multilateration (WAM) systems are being established. These sensors can
      track aircraft positions more accurately than existing radar and can compensate
      for the blind spots in aircraft surveillance. In this paper, we applied a novel
      sensor fusion method with Interacting Multiple Model (IMM) filter to GBAS, ADS-B,
      MLAT, and WAM data in order to improve the reliability of the aircraft position.
      Results of performance analysis show that the position accuracy is improved by
      the proposed sensor fusion method with the IMM filter.

PMID- 23535716
TI  - Ratiometric optical temperature sensor using two fluorescent dyes dissolved in an
      ionic liquid encapsulated by Parylene film.
AB  - A temperature sensor that uses temperature-sensitive fluorescent dyes is
      developed. The droplet sensor has a diameter of 40 um and uses 1 g/L of Rhodamine
      B (RhB) and 0.5 g/L of Rhodamine 110 (Rh110), which are fluorescent dyes that are
      dissolved in an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate) to
      function as temperature indicators. This ionic liquid is encapsulated using
      vacuum Parylene film deposition (which is known as the Parylene-on-liquid
      deposition (PoLD) method). The droplet is sealed by the chemically stable and
      impermeable Parylene film, which prevents the dye from interacting with the
      molecules in the solution and keeps the volume and concentration of the
      fluorescent material fixed. The two fluorescent dyes enable the temperature to be
      measured ratiometrically such that the droplet sensor can be used in various
      applications, such as the wireless temperature measurement of microregions. The
      sensor can measure the temperature of such microregions with an accuracy of 1.9 
      degrees C, a precision of 3.7  degrees C, and a fluorescence intensity change
      sensitivity of 1.0%/K. The sensor can measure temperatures at different sensor
      depths in water, ranging from 0 to 850 um. The droplet sensor is fabricated using
      microelectromechanical system (MEMS) technology and is highly applicable to lab
      on-a-chip devices.

PMID- 23535717
TI  - A two-dimensional laser scanning mirror using motion-decoupling electromagnetic
      actuators.
AB  - This work proposes a two-dimensional (2-D) laser scanning mirror with a novel
      actuating structure composed of one magnet and two coils. The mirror-actuating
      device generates decoupled scanning motions about two orthogonal axes by
      combining two electromagnetic actuators of the conventional moving-coil and the
      moving-magnet types. We implement a finite element analysis to calculate magnetic
      flux in the electromagnetic system and experiments using a prototype with the
      overall size of 22 mm (W) * 20 mm (D) * 15 mm (H) for the mirror size of 8 mm * 8
      mm. The upper moving-coil type actuator to rotate only the mirror part has the
      optical reflection angle of 15.7 degrees  at 10 Hz, 90 degrees  at the resonance
      frequency of 60 Hz at +/-3 V (+/-70 mA) and the bandwidth of 91 Hz. The lower
      moving-magnet type actuator has the optical reflection angle of 16.20 degrees  at
      10 Hz and 50 degrees  at the resonance frequency of 60 Hz at +/-5 V (+/-34 mA)
      and the bandwidth of 88 Hz. The proposed compact and simple 2-D scanning mirror
      has advantages of large 2-D angular deflections, wide frequency bandwidth and low
      manufacturing cost.

PMID- 23535718
TI  - Formation, structure, and reactivity of meso-tetraaryl-chlorolactones, 
      porpholactams, and -chlorolactams, porphyrin and chlorin analogues incorporating
      oxazolone or imidazolone moieties.
AB  - Reaction of known meso-tetraarylporpholactone free bases 3, made from the
      corresponding porphyrins, with hydrazine produces three products: It converts the
      lactone functional group into an N-aminolactam moiety, generating porphyrin-like
      N-aminoporpholactams 8. It also reduces regioselectively the beta,beta'-double
      bond of the pyrrolic moiety opposite to the imidazolone in both the starting
      material and the N-aminoporpholactam, thus forming the chlorin-like
      chlorolactones 7 and N-aminochlorolactams 9. An equivalent set of reaction
      products is also derived from the reaction of porpholactones 3 with
      tosylhydrazide. Reductive N-N cleavage of the N-aminoporpholactams 8 generated
      the parent porpholactams 10. The molecular structures of all key compounds were
      shown by single crystal X-ray diffraction to be essentially planar. Porpholactam
      10a can be converted in two steps (enolization and halogenation alpha to the
      imine, followed by reductive removal of the halogen) to known imidazoloporphyrin
      5a, thus constituting the third independent pathway to replace a beta-carbon of a
      tetraphenylporphyrin by a nitrogen. All these transformations show the
      flexibility of our 'porphyrin breaking and mending' strategy toward the synthesis
      of novel porphyrin and chlorin analogues incorporating non-pyrrolic heterocycles
      that carry functionalities at their periphery.

PMID- 23535720
TI  - Predicting the influence of common variants.
AB  - An ever-larger proportion of the liability to common and complex disease can be
      obtained by progressively larger studies. However, for most diseases, the sample
      sizes required to gain usable predictions will be out of reach of sequencing
      technologies for the foreseeable future. Array-based genotyping genome-wide
      association studies(GWAS) still offer a reliable harvest of biological hypotheses
      for many diseases, together with the secondary benefit of slowly improving
      prediction.

PMID- 23535719
TI  - Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task
      specific and age-dependent.
AB  - We recently generated an advanced mouse model of Alzheimer's disease (AD) by
      targeted knock-in of single-copy mutated human amyloid precursor-protein (APP)
      and tau genes, crossed with a non-symptomatic presenilin (PS1A246E) over
      expressing mouse line. These PLB1Triple mice presented with age-dependent and AD
      relevant phenotypes. Homozygous PLB1Triple mice aged 4-12 months were assessed
      here in a battery of spatial learning tasks: Exp.1 radial-arm water maze (spatial
      reference and working memory) Exp.2 open-field water maze (spatial reference
      memory); Exp.3 home cage observation system with spatial learning (IntelliCage);
      Exp.4 spontaneous object recognition (SOR; novel object and spatial object
      shift). A separate test with high-expression transgenic APP mice matching the
      design of experiment 1 was also performed. Spatial deficits in PLB1Triple mice
      were confirmed at 12, but not 4 months in both water maze tasks. PSAPP mice, by
      contrast, presented with severe yet non-progressive spatial learning deficits
      already at 4 months. During tests of spatial learning in SOR and IntelliCage,
      PLB1Triple mice neither acquired the location of the water-rewarded corner, nor
      recognize novel or spatially shifted objects at 4 months, indicating these
      protocols to be more sensitive than the water maze. Collectively and in line with
      AD symptomatology, PLB1Triple mice present with a graded and progressive age
      dependent loss of spatial memory that can be revealed by the use of a battery of
      tasks. With the emergence of subtle deficits progressively increasing in
      severity, PLB1Triple mice may offer a more patho-physiologically relevant model
      of dementia than aggressive expression models. 

PMID- 23535721
TI  - iCOGS collection provides a collaborative model. Foreword.

PMID- 23535722
TI  - Turning of COGS moves forward findings for hormonally mediated cancers.
AB  - The large-scale Collaborative Oncological Gene-environment Study (COGS) presents
      new findings that further characterize the genetic bases of breast, ovarian and
      prostate cancers. We summarize and provide insights into this collection of
      papers from COGS and discuss the implications of the results and future
      directions for such efforts.

PMID- 23535723
TI  - Public health implications from COGS and potential for risk stratification and
      screening.
AB  - The PHG Foundation led a multidisciplinary program, which used results from COGS
      research identifying genetic variants associated with breast, ovarian and
      prostate cancers to model risk-stratified prevention for breast and prostate
      cancers. Implementing such strategies would require attention to the use and
      storage of genetic information, the development of risk assessment tools, new
      protocols for consent and programs of professional education and public
      engagement.

PMID- 23535730
TI  - GWAS meta-analysis and replication identifies three new susceptibility loci for
      ovarian cancer.
AB  - Genome-wide association studies (GWAS) have identified four susceptibility loci
      for epithelial ovarian cancer (EOC), with another two suggestive loci reaching
      near genome-wide significance. We pooled data from a GWAS conducted in North
      America with another GWAS from the UK. We selected the top 24,551 SNPs for
      inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping
      in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from
      the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and
      17q21 that were previously found to have associations close to genome-wide
      significance and identified three loci newly associated with risk: two loci
      associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 * 10(-9)) and 10p12
      (rs1243180, P = 1.8 * 10(-8)) and another locus specific to the serous subtype at
      17q12 (rs757210, P = 8.1 * 10(-10)). An integrated molecular analysis of genes
      and regulatory regions at these loci provided evidence for functional mechanisms
      underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian
      cancer.

PMID- 23535729
TI  - Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
AB  - Breast cancer is the most common cancer among women. Common variants at 27 loci
      have been identified as associated with susceptibility to breast cancer, and
      these account for ~9% of the familial risk of the disease. We report here a meta
      analysis of 9 genome-wide association studies, including 10,052 breast cancer
      cases and 12,575 controls of European ancestry, from which we selected 29,807
      SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880
      controls of European ancestry from 41 studies in the Breast Cancer Association
      Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping
      experiment involving four consortia (Collaborative Oncological Gene-environment
      Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS,
      comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer
      susceptibility loci at genome-wide significance (P < 5 * 10(-8)). Further
      analyses suggest that more than 1,000 additional loci are involved in breast
      cancer susceptibility.

PMID- 23535732
TI  - Identification of 23 new prostate cancer susceptibility loci using the iCOGS
      custom genotyping array.
AB  - Prostate cancer is the most frequently diagnosed cancer in males in developed
      countries. To identify common prostate cancer susceptibility alleles, we
      genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from
      25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL
      Consortium. Twenty-three new prostate cancer susceptibility loci were identified
      at genome-wide significance (P < 5 * 10(-8)). More than 70 prostate cancer
      susceptibility loci, explaining ~30% of the familial risk for this disease, have
      now been identified. On the basis of combined risks conferred by the new and
      previously known risk loci, the top 1% of the risk distribution has a 4.7-fold
      higher risk than the average of the population being profiled. These results will
      facilitate population risk stratification for clinical studies.

PMID- 23535736
TI  - Stepwise behaviour of magnetization temperature dependence in iron nanoparticle
      assembled films.
AB  - An unusual stepwise behaviour is reported in the temperature dependence of the
      zero field cooled magnetization in iron nanoparticle dense films produced by
      ultra-short pulsed laser deposition assisted by irradiation of nanoparticles with
      a nanosecond UV laser pulse, appropriately delayed, during their flight from the
      target to the substrate. This behaviour, induced by the particle system's
      morphology, characterized by clusters of tightly coupled nanoparticles as well as
      by some voids between them, is ascribed to the competition between Zeeman energy
      density, intracluster anisotropy energy density and intercluster exchange energy
      density. A phenomenological model and Monte Carlo simulations are reported, which
      support the proposed interpretation.

PMID- 23535735
TI  - Inorganic coatings for optimized non-viral transfection of stem cells.
AB  - "Biomimetic" approaches for heterogeneous growth of inorganic coatings have
      become particularly widespread in biomedical applications, where calcium
      phosphate (CaP) mineral coatings are used to improve biomedical implants. Changes
      in coating properties can influence the effects of mineral coatings on adjacent
      cells, but to date it has not been practical to systematically vary inorganic
      coating properties to optimize specific cell behaviors. Here, we present an
      approach to grow CaP mineral coatings in an enhanced throughput format to
      identify unprecedented capabilities in non-viral gene delivery. Subtle changes in
      coating properties resulted in widely variable transfection, and optimized
      coatings led to greater than 10-fold increases in transgene expression by
      multiple target cell types when compared to standard techniques. The enhanced
      transfection observed here is substrate-mediated, and related to the
      characteristics of the local environment near the surface of dissolving mineral
      coatings. These findings may be particularly translatable to medical device
      applications.

PMID- 23535737
TI  - Fabrication of hand-in-hand nanostructure for one-step protein detection.
AB  - A new strategy to fabricate an aptamer-protein nanowire at an electrode surface
      is reported in this paper, and a simple electrochemical method to determine the
      concentration of a protein is proposed with high sensitivity and selectivity.

PMID- 23535734
TI  - Identification of seven loci affecting mean telomere length and their association
      with disease.
AB  - Interindividual variation in mean leukocyte telomere length (LTL) is associated
      with cancer and several age-associated diseases. We report here a genome-wide
      meta-analysis of 37,684 individuals with replication of selected variants in an
      additional 10,739 individuals. We identified seven loci, including five new loci,
      associated with mean LTL (P < 5 * 10(-8)). Five of the loci contain candidate
      genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in
      telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several
      cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a
      genetic risk score analysis combining lead variants at all 7 loci in 22,233
      coronary artery disease cases and 64,762 controls showed an association of the
      alleles associated with shorter LTL with increased risk of coronary artery
      disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P =
      0.014). Our findings support a causal role of telomere-length variation in some
      age-related diseases.

PMID- 23535738
TI  - The Osteoporosis Society of Hong Kong (OSHK): 2013 OSHK guideline for clinical
      management of postmenopausal osteoporosis in Hong Kong.

PMID- 23535739
TI  - Immobilized purine nucleoside phosphorylase from Schistosoma mansoni for specific
      inhibition studies.
AB  - The parasite Schistosoma mansoni (Sm) depends exclusively on the salvage pathway
      for its purine requirements. The enzyme purine nucleoside phosphorylase (PNP) is,
      therefore, a promising target for development of antischistosomal agents and an
      assay for screening of inhibitors. To enable this, immobilized SmPNP reactors
      were produced. By quantification of hypoxanthine by liquid chromatography,
      kinetic constants (K M) for the substrate inosine were determined for the free
      and immobilized enzyme as 110 +/- 6.90 MUmol L (-1) and 164 +/- 13.4 MUmol L (
      1), respectively, indicating that immobilization did not affect enzyme activity.
      Furthermore, the enzyme retained 25 % of its activity after four months. Non
      Michaelis kinetics for the phosphate substrate, and capacity for Pi-independent
      hydrolysis were also demonstrated, despite the low rate of enzymatic catalysis.
      Use of an SmPNP immobilized enzyme reactor (IMER) for inhibitor-screening assays
      was demonstrated with a small library of 9-deazaguanine analogues. The method had
      high selectivity and specificity compared with screening by use of the free
      enzyme by the Kalckar method, and furnished results without the need for
      verification of the absence of false positives.

PMID- 23535740
TI  - LC-QTOF/MS metabolomic profiles in human plasma after a 5-week high dietary fiber
      intake.
AB  - The objective was to investigate the alterations of plasma metabolome profiles to
      identify exposure and effect markers of dietary fiber intake. Subjects (n = 25)
      aged 58.6 (1.1) years (mean and SD) with a body mass index of 26.6 (0.5) kg/m(2)
      were given a high fiber (HF) and a low fiber (LF) diet, in a 5-week randomized
      controlled crossover intervention. The HF diet consisted of oat bran, rye bran,
      and sugar beet fiber incorporated into test food products, whereas the LF diet
      was made of equivalent food products to the HF diet, but without adding fibers.
      Blood plasma samples were collected at the start and end of each intervention
      period and analyzed by LC-QTOF/MS. In total, 6 features in positive mode and 14
      features in negative mode were significantly different between the HF and the LF
      diet (p < 0.01, q < 0.05). Two markers, 2,6-dihydroxybenzoic acid and 2
      aminophenol sulfate, were increased after HF diet, along with a tentatively
      identified saponin derived from oat avenacosides. The untargeted metabolomics
      approach enabled the identification of two new markers of dietary fiber intake in
      human plasma. Further studies will be needed to verify if these markers could
      serve as compliance markers of fiber intake.

PMID- 23535741
TI  - Method development and validation for rat serum fingerprinting with CE-MS:
      application to ventilator-induced-lung-injury study.
AB  - In the search for a noninvasive and reliable rapid screening method to detect
      biomarkers, a metabolomics fingerprinting approach was developed and applied to
      rat serum samples using capillary electrophoresis coupled to an electrospray
      ionization-time of flight-mass spectrometer (CE-TOF-MS). An ultrafiltration
      method was used for sample pretreatment. To evaluate performance the method was
      validated with carnitine, choline, ornithine, alanine, acetylcarnitine, betaine,
      and citrulline, covering the entire electropherogram of pool of rat serum. The
      linearity for all metabolites was >0.99, with good recovery and precision.
      Approximately 34 compounds were also confirmed in the pool of rat serum. The
      method was successfully applied to real serum samples from rats with ventilator
      induced lung injury, an experimental rat model for acute lung injury (ALI),
      giving a total of 1163 molecular features. By use of univariate and multivariate
      statistics 18 significant compounds were found, of which five were confirmed. The
      involvement of arginase and nitric oxide synthase has been proved for other lung
      diseases, meaning the increase of asymmetric dimethyl arginine (ADMA) and
      ornithine and the decrease of arginine found were in accordance with published
      literature. Ultimately this fingerprinting approach offers the possibility of
      identifying biomarkers that could be regularly screened for as part of routine
      disease control. In this way it might be possible to prevent the development of
      ALI in patients in critical care units.

PMID- 23535731
TI  - Multiple independent variants at the TERT locus are associated with telomere
      length and risks of breast and ovarian cancer.
AB  - TERT-locus SNPs and leukocyte telomere measures are reportedly associated with
      risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we
      analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n =
      39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls.
      Leukocyte telomere measurements were also available for 53,724 participants. Most
      associations cluster into three independent peaks. The minor allele at the peak 1
      SNP rs2736108 associates with longer telomeres (P = 5.8 * 10(-7)), lower risks
      for estrogen receptor (ER)-negative (P = 1.0 * 10(-8)) and BRCA1 mutation carrier
      (P = 1.1 * 10(-5)) breast cancers and altered promoter assay signal. The minor
      allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 *
      10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 * 10(
      15)) and greater promoter activity. The minor alleles at the peak 3 SNPs
      rs10069690 and rs2242652 increase ER-negative (P = 1.2 * 10(-12)) and BRCA1
      mutation carrier (P = 1.6 * 10(-14)) breast and invasive ovarian (P = 1.3 * 10(
      11)) cancer risks but not via altered telomere length. The cancer risk alleles of
      rs2242652 and rs10069690, respectively, increase silencing and generate a
      truncated TERT splice variant.

PMID- 23535733
TI  - Genome-wide association studies identify four ER negative-specific breast cancer
      risk loci.
AB  - Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers,
      with a higher proportion occurring in younger women and women of African
      ancestry. The etiology and clinical behavior of ER-negative tumors are different
      from those of tumors expressing ER (ER positive), including differences in
      genetic predisposition. To identify susceptibility loci specific to ER-negative
      disease, we combined in a meta-analysis 3 genome-wide association studies of
      4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40
      follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom
      Illumina array, iCOGS, developed by the Collaborative Oncological Gene
      environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 * 10(-12) and
      LGR6, P = 1.4 * 10(-8)), 2p24.1 (P = 4.6 * 10(-8)) and 16q12.2 (FTO, P = 4.0 *
      10(-8)), were associated with ER-negative but not ER-positive breast cancer (P >
      0.05). These findings provide further evidence for distinct etiological pathways
      associated with invasive ER-positive and ER-negative breast cancers.

PMID- 23535742
TI  - A fast method for the quantitation of key metabolites of the methionine pathway
      in liver tissue by high-resolution mass spectrometry and hydrophilic interaction
      ultra-performance liquid chromatography.
AB  - We developed an assay for the extraction and simultaneous quantitation of five
      key metabolites of the methionine metabolic pathway in liver tissue. The
      metabolites included were 5'-methylthioadenosine, methionine, homocysteine, S
      adenosyl-L-homocysteine, and S-adenosyl-L-methionine. The metabolites were
      extracted using a bead-based homogenization method, and quantitation was carried
      out using hydrophilic interaction chromatography and time-of-flight mass
      spectrometry. The extraction procedure was optimized by testing the effect of
      various solvent combinations. The chromatographic method was optimized for peak
      shape, signal intensity, and carry-over. With a total chromatographic run time of
      5 min, this assay is suitable for the analysis of large sample sets. Time-of
      flight mass spectrometry provided high mass accuracy which, combined with isotope
      pattern matching and use of chemical standards, guarantees high specificity.
      Moreover, by operating the mass spectrometer in enhanced duty cycle mode the
      signal strength for the analytes increased three- to tenfold in comparison with
      the generic full-scan mode. For quantitation, a matrix-spiked calibration method
      was used. The lowest analyte levels detected and quantified using our method were
      within the range of concentrations found in the liver. The inter-day coefficients
      of variance for the analytes were between 5 and 15% in pooled tissue samples.
      Interestingly, the CVs between individual liver tissue aliquots were about twice
      as high. Additional experiments suggested that this higher variability was caused
      by uneven distribution of the analytes within the liver. In conclusion, an
      optimized and robust assay is now available for the extraction and quantification
      of key metabolites in the methionine metabolic pathway.

PMID- 23535743
TI  - LC/ESI-MS/MS method for quantification of 28 synthetic cannabinoids in neat oral
      fluid and its application to preliminary studies on their detection windows.
AB  - Serum and urine samples are commonly used for the analysis of synthetic
      cannabinoids in biofluids; however, their utilization as analytical matrices for
      drug abstinence control features some substantial drawbacks. While for blood
      collection invasive sampling is inevitable, the urinary analysis of synthetic
      cannabinoids is limited by the lack of available reference standards of the
      respective major metabolites. Moreover, the long detectability of synthetic
      cannabinoids in both matrices hampers the identification of a recent synthetic
      cannabinoid use. This article describes the development, validation and
      application of an LC/ESI-MS/MS method for the quantification of 28 synthetic
      cannabinoids in neat oral fluid (OF) samples. OF samples were prepared by protein
      precipitation using ice-cold acetonitrile. Chromatographic separation was
      achieved by gradient elution on a Luna Phenyl Hexyl column (50 * 2 mm, 5 MUm),
      while detection was carried out on a QTrap 4000 instrument in positive ionization
      mode. The limits of detection ranged from 0.02 to 0.40 ng/mL, whereas the lower
      limits of quantification ranged from 0.2 to 4.0 ng/mL. The method was applied to
      authentic samples collected during two preliminary studies in order to obtain
      insights into the general detectability and detection windows of synthetic
      cannabinoids in this matrix. The results indicate that synthetic cannabinoids are
      transferred from the blood stream into OF and vice versa only at a very low rate.
      Therefore, positive OF samples are due to contamination of the oral cavity during
      smoking. As these drug-contaminations could be detected up to approximately 2
      days, neat oral fluid appears to be well suited for detection of a recent
      synthetic cannabinoid use.

PMID- 23535744
TI  - Use of gel permeation chromatography for clean-up in the analysis of
      coccidiostats in eggs by liquid chromatography-tandem mass spectrometry.
AB  - An analytical method for determination and confirmation of nine coccidiostatics
      in eggs is reported. Ethyl acetate is used as extraction solvent, with
      satisfactory results, and simple automated clean-up is based on gel-permeation
      chromatography (GPC) . The target compounds are then analysed by liquid
      chromatography-electrospray ionization-tandem mass spectrometry. The method was
      validated in-house in accordance with Commission Decision 2002/657/EC. Trueness
      and precision were determined at four concentrations, and the mean errors
      obtained were <10 %, with relative standard deviations ranging from 3 to 18 %.
      For three non-authorized coccidiostatics (clopidol, ethopabate, and ronizadole),
      decision limit and detection capability were in the ranges 0.12-0.16 and 0.18
      0.23 MUg kg(-1), respectively. The results obtained prove the suitability of this
      new analytical method for routine monitoring of these substances in eggs.

PMID- 23535746
TI  - Nano-tungsten carbide decorated graphene as co-catalysts for enhanced hydrogen
      evolution on molybdenum disulfide.
AB  - A novel electrocatalyst of layered MoS2 supported on reduced graphene oxide (RGO)
      decorated with nano-sized tungsten carbide (WC) shows an enhanced catalytic
      performance in the hydrogen evolution reaction, which could be attributed to the
      presence of a conductive and electrocatalytically-active nano-WC dispersant and
      the positive synergistic effect between nano-WC/RGO and layered MoS2.

PMID- 23535745
TI  - Assaying the efficacy of dual-antiplatelet therapy: use of a controlled-shear
      rate microfluidic device with a well-defined collagen surface to track dynamic
      platelet adhesion.
AB  - We report the development and demonstration of an assay that distinguishes the
      pharmacological effects of two widely used antiplatelet therapies, aspirin (COX-1
      inhibitor) and clopidogrel (P2Y12 inhibitor). Whole blood is perfused through a
      low-volume microfluidic device in contact with a well-characterized
      (ellipsometry, atomic force microscopy) acid-soluble type I collagen surface.
      Whole human blood treated in vitro with a P2Y12 inhibitor 2-methylthioadenosine
      5'-monophosphate triethylammonium salt (2-MeSAMP) extended the time to the start
      of platelet recruitment, i.e., platelet binding to the collagen surface.
      Treatment with 2-MeSAMP also slowed the rate of aggregate buildup, with an
      overall reduced average platelet aggregate area after 8 min of constant blood
      flow. A far smaller effect was observed for in vitro treatment with aspirin, for
      which the rate of change of surface coverage is indistinguishable from controls.
      In whole blood obtained from patients under treatment with dual-antiplatelet
      therapy (aspirin and clopidogrel), a significant extension of time to platelet
      recruitment was observed along with a slowed rate of aggregate buildup and an
      average aggregate size approximately half that of control measurements.
      Differentiation of the pharmacological effects of these two well-targeted
      antiplatelet pathways suggests a role for this assay in determining the
      antiplatelet effects of these and related new therapeutics in clinical settings.

PMID- 23535747
TI  - Treatment of E. boehmi infection in a mixed-breed dog using milbemycin oxime.
AB  - Numerous bipolar plugged capillarid eggs were detected on a routine centrifugal
      fecal flotation examination of a 2 yr old castrated male boxer-Chinese shar pei
      mixed-breed. The eggs were identified as Eucoleus boehmi (E. boehmi), the nasal
      capillarid, based on size and shell wall surface morphology. The dog had a
      history of chronic sneezing (> 5 times/day) and intermittent postexercise nasal
      discharge. Currently, there are no anthelmintics approved for use in dogs for the
      treatment of E. boehmi. Treatment of the dog with 0.5-1 mg/kg milbemycin oxime
      was ineffective, but treatment with 2 mg/kg milbemycin oxime resulted in negative
      fecal examinations 7-28 days and 5 mo posttreatment. The dog's postexertion nasal
      discharge greatly lessened, and the sneezing behavior improved (it was only noted
      2-3 times/wk), but neither the discharge nor sneezing completely resolved
      following the anthelmintic treatments. Use of milbemycin oxime at an increased
      dose (2 mg/kg) appeared to be an effective treatment against E. boehmi infection
      in this dog based on clinical response and the cessation of fecal egg shedding.

PMID- 23535748
TI  - Efficacy of incisional gastropexy for prevention of GDV in dogs.
AB  - Incisional gastropexy (IG) is routinely performed as either a prophylactic
      procedure to prevent occurrence of gastric dilatation-volvulus (GDV) or at the
      time of surgical correction of GDV to prevent recurrence. Despite its common use,
      the long-term efficacy of the IG procedure has not been reported. The hypothesis
      of this study was that IG performed either during surgical treatment of GDV or as
      a prophylactic measure would effectively prevent GDV. Medical records of 61 dogs
      undergoing IG following either gastric derotation for treatment of GDV or as a
      prophylactic procedure were evaluated retrospectively. Median follow-up time for
      all dogs was 717 days (range, 49-2,511 days). Of the 61 dogs, 27 had prophylactic
      IG performed. The remaining 34 dogs presented for GDV and had an IG performed
      during surgical treatment of GDV. No dog experienced GDV after IG. Recurrence of
      gastric dilatation (GD) alone was noted in 3 of 34 patients (8.8%) undergoing IG
      during surgery for GDV and in 3 of 27 patients (11.1%) treated prophylactically
      with IG. This study confirmed the efficacy of IG for the long-term prevention of
      GDV in dogs.

PMID- 23535749
TI  - Postoperative complications following TECA-LBO in the dog and cat.
AB  - The medical records for 133 total ear canal ablations combined with lateral bulla
      osteotomies (TECA-LBOs) performed on 82 dogs (121 ears) and 11 cats (12 ears)
      between 2004 and 2010 were reviewed to determine if the duration of preoperative
      clinical signs was associated with the incidence of postoperative facial nerve
      injury and Horner's syndrome. Other perioperative complications, such as a head
      tilt, nystagmus, incisional drainage, draining tracts, hearing loss, as well as
      bacterial culture results, were noted. Postoperative facial nerve paresis
      occurred in 36 of 133 ears (27.1%), and paralysis occurred in 29 of 133 ears
      (21.8%), with no significant difference between species. Thus, postoperative
      facial nerve deficits occurred in 48.9% of ears. The median duration of
      clinically evident temporary facial nerve deficits was 2 wk for dogs and 4 wk for
      cats. Dogs had a significantly longer duration of preoperative clinical signs and
      were less likely than cats to have a mass in the ear canal. Dogs were less likely
      to have residual (> 1 yr) postoperative facial nerve deficits. The incidence of
      postoperative Horner's syndrome was significantly higher in cats than dogs. The
      duration of preoperative clinical signs of ear disease was not associated with
      postoperative facial nerve deficits.

PMID- 23535750
TI  - Survival after anaphylaxis induced by a bumblebee sting in a dog.
AB  - A 3.5 yr old castrated male miniature schnauzer was referred with a history of
      collapse after a bee sting to the left hind limb. At the time of presentation, 14
      hr after the sting, the dog was hypotensive, comatose, seizuring, and had a brief
      period of cardiac arrest. Over the following 48 hr, the dog developed azotemia,
      severely elevated liver enzyme levels, hypertension, hematochezia, hematemesis,
      and disseminated intravascular coagulation (DIC). The dog's neurologic status
      improved slowly, but significant behavioral abnormalities remained. The dog was
      discharged after 7 days with ongoing polyuria, polydipsia, and behavioral
      changes. The polydipsia and polyuria resolved within a few days, but the
      behavioral changes continued for 6 wk. Reports of anaphylaxis from any cause are
      sparse in the veterinary literature. This is the first report of suspected
      anaphylaxis following a bee sting. There are no previous reports of behavioral
      changes after physical recovery from anaphylaxis.

PMID- 23535751
TI  - Bifocal femoral deformity correction and lengthening using a circular fixator
      construct in a dog.
AB  - A 7 mo old male rottweiler was evaluated for a right hind limb lameness caused by
      malunion of a Salter-Harris type II fracture. Radiographs and computed tomography
      (CT) revealed that the right distal femur had valgus, procurvatum, external
      rotation, and was 35% (70 mm) shorter than the contralateral femur. Distal
      femoral wedge ostectomies were performed to acutely correct the angular and
      rotational deformities. Lengthening of the femur was accomplished by distraction
      osteogenesis performed over 53 days at a second, proximal diaphyseal osteotomy
      using a circular fixator construct. This bifocal approach yielded approximately
      30 mm of femoral lengthening and a confluent column of regenerate bone that
      bridged the distraction gap. When evaluated 14 mo after surgery, the dog held the
      right hip, stifle, and hock in a slightly extended posture when standing and had
      a subtle asymmetric hind limb gait. The stride of the right hind limb was
      slightly shortened with compensatory circumduction of the left hind limb during
      the swing phase of the stride.

PMID- 23535752
TI  - Clinicopathologic significance of histologic grade, pgp, and p53 expression in
      canine lymphoma.
AB  - To characterize the expression of P-glycoprotein (Pgp) and p53 in different
      histologic grades of canine multicentric lymphosarcoma (LSA), 31 cases of LSA
      without prior treatment were studied. The expression levels of the Pgp and p53
      proteins were evaluated for their clinicopathologic significance among standard
      histologic evaluation. Immunohistochemistry (IHC) was performed on formalin
      fixed, paraffin-embedded archival samples of 31 previously untreated LSA cases to
      detect the expression of Pgp and p53. All dogs were subsequently treated with a
      combination chemotherapy protocol. Remission and survival durations were
      evaluated for correlation with histologic grade and presence of drug resistance
      markers. Of the 31 cases, 24 (80%) and 7 (22%) were positive for Pgp and p53,
      respectively. Overall, the median survival and duration of remission in the study
      was 246 days and 137 days, respectively. The National Cancer Institute working
      formulation histologic grade was not associated with either survival or duration
      of first remission (DOR). The Pgp protein expression and DOR and survival was not
      statistically significant. Expression of p53 was statistically correlated with
      survival.

PMID- 23535753
TI  - Accuracy of US-guided FNA of focal liver lesions in dogs: 140 cases (2005-2008).
AB  - Medical records from dogs having abdominal ultrasound (US) performed between
      March 2005 and October 2008 were reviewed for detection of focal liver lesions
      (FLL) with both cytologic and histologic sampling. Samples were classified as to
      either the presence or absence of major categories of pathologic processes,
      including malignant neoplasia, inflammation, hyperplasia/benign neoplasia,
      vacuolar change, extramedullary hematopoeisis, cholestasis, necrosis, and no
      microscopic abnormalities. Evaluation of selection bias was performed by review
      of the relative distribution of cytologic diagnoses for cases with histology
      compared with cases excluded from the comparison analysis because histology
      results were not available. Cytology had the highest sensitivity for vacuolar
      change (57.9%), followed by neoplasia (52.0%). Cytology had the highest positive
      predictive value (PPV) for neoplasia (86.7%) followed by vacuolar change (51.6%).
      Cytology had lower sensitivity and PPVs for inflammation, necrosis, and
      hyperplasia. The ability of cytology to characterize disease in canine FLL varies
      by pathologic process. Clinicians can have a high degree of confidence when a
      cytologic diagnosis of neoplasia is given; however, cytology is less reliable for
      excluding the potential for neoplasia. Cytology has a low sensitivity and PPV for
      inflammation and a limited diagnostic performance for the diagnosis of vacuolar
      change.

PMID- 23535754
TI  - Clinical and laboratory findings in border collies with presumed hereditary
      juvenile cobalamin deficiency.
AB  - Juvenile cobalamin deficiency is a rare disease in border collies and its
      diagnosis requires a high level of clinical suspicion. The goal of this study was
      to increase awareness of this disease by describing the clinical and laboratory
      findings in four young border collies with inherited cobalamin deficiency. The
      median age of the dogs was 11.5 mo (range, 8-42 mo), and two of the four dogs
      were full siblings. Clinical signs included intermittent lethargy (n = 4), poor
      body condition (n = 4), odynophagia (n = 2), glossitis (n = 1), and
      bradyarrhythmia (n = 1). Pertinent laboratory abnormalities were mild to moderate
      normocytic nonregenerative anemia (n = 3), increased aspartate aminotransferase
      (AST) activity (n = 3), and mild proteinuria (n = 3). All of the dogs had serum
      cobalamin levels below the detection limit of the assay, marked methylmalonic
      aciduria, and hyperhomocysteinemia. Full clinical recovery was achieved in all
      dogs with regular parenteral cobalamin supplementation, and laboratory
      abnormalities resolved, except the proteinuria and elevated AST activity
      persisted. This case series demonstrates the diverse clinical picture of primary
      cobalamin deficiency in border collies. Young border collies presenting with
      ambiguous clinical signs should be screened for cobalamin deficiency.

PMID- 23535755
TI  - Predisposing factors for colonic torsion/volvulus in dogs: a retrospective study
      of six cases (1992-2010).
AB  - The purposes of this retrospective study were to review cases of colonic
      torsion/volvulus between July 1992 and August 2010 and to determine if any
      predisposing factors exist for the development of this condition. Six dogs were
      diagnosed with colonic torsion/volvulus during the study period. Four dogs had a
      history of previous gastric dilation-volvulus (GDV) with prophylactic gastropexy.
      Three of six dogs diagnosed with colonic torsion/volvulus had large intestinal
      entrapment and strangulation around the gastropexy site at the time of surgery.
      The history, clinical signs, physical examination, and radiologic findings were
      not specific for colonic torsion/volvulus in any dog. Early exploratory
      laparotomy was indicated to confirm the diagnosis and perform surgical correction
      of the affected bowel segments. Three of five dogs that underwent surgery had a
      left abdominal wall colopexy performed. All five dogs that underwent surgery in
      this study survived postoperatively. One patient was euthanized without surgical
      intervention. Results suggest that colonic torsion/volvulus should be considered
      in any large-breed dog with nonspecific gastrointestinal clinical signs and a
      history of previous gastropexy. Early recognition and prompt treatment of this
      condition may result in a good outcome.

PMID- 23535756
TI  - Methocarbamol CRI for symptomatic treatment of pyrethroid intoxication: a report
      of three cases.
AB  - Pyrethroids are popular for use in companion animals due to their relatively low
      mammalian toxicity and efficacy against arthropods. Nonetheless, pyrethroid
      intoxication has been reported in cats and dogs, and cats appear to be more
      susceptible due to difficulty in biotransformation and excretion of pyrethroids.
      Pyrethroid intoxications are generally due to either the improper use or
      accidental ingestion of approved products. Methocarbamol, given as intermittent
      injections, is a common first-line treatment choice for the tremors associated
      with pyrethroid intoxication. Two cats and one dog were treated with a
      methocarbamol continuous rate infusion (CRI) for pyrethroid intoxication.
      Clinical signs of toxicity resolved within a few hr in all three cases, with no
      adverse drug effects. A methocarbamol CRI can be considered in animals presenting
      with pyrethroid intoxication. 

PMID- 23535757
TI  - Diagnosis and management of Q fever--United States, 2013: recommendations from
      CDC and the Q Fever Working Group.
AB  - Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause
      acute or chronic illness in humans. Transmission occurs primarily through
      inhalation of aerosols from contaminated soil or animal waste. No licensed
      vaccine is available in the United States. Because many human infections result
      in nonspecific or benign constitutional symptoms, establishing a diagnosis of Q
      fever often is challenging for clinicians. This report provides the first
      national recommendations issued by CDC for Q fever recognition, clinical and
      laboratory diagnosis, treatment, management, and reporting for health-care
      personnel and public health professionals. The guidelines address treatment of
      acute and chronic phases of Q fever illness in children, adults, and pregnant
      women, as well as management of occupational exposures. These recommendations
      will be reviewed approximately every 5 years and updated to include new published
      evidence.

PMID- 23535758
TI  - The impact of a father's presence during newborn resuscitation: a qualitative
      interview study with healthcare professionals.
AB  - OBJECTIVE: To explore healthcare professionals' experiences around the time of
      newborn resuscitation in the delivery room, when the baby's father was present.
      DESIGN: A qualitative descriptive, retrospective design using the critical
      incident approach. Tape-recorded semistructured interviews were undertaken with
      healthcare professionals involved in newborn resuscitation. Participants recalled
      resuscitation events when the baby's father was present. They described what
      happened and how those present, including the father, responded. They also
      reflected upon the impact of the resuscitation and the father's presence on
      themselves. Participant responses were analysed using thematic analysis. SETTING:
      A large teaching hospital in the UK. PARTICIPANTS: Purposive sampling was
      utilised. It was anticipated that 35-40 participants would be recruited. Forty
      nine potential participants were invited to take part. The final sample consisted
      of 37 participants including midwives, obstetricians, anaesthetists, neonatal
      nurse practitioners, neonatal nurses and paediatricians. RESULTS: Four themes
      were identified: 'whose role?' 'saying and doing' 'teamwork' and 'impact on me'.
      While no-one was delegated to support the father during the resuscitation,
      midwives and anaesthetists most commonly took on this role. Participants felt the
      midwife was the most appropriate person to support fathers. All healthcare
      professional groups said they often did not know what to say to fathers during
      prolonged resuscitation. Teamwork was felt to be of benefit to all concerned,
      including the father. Some paediatricians described their discomfort when fathers
      came to the resuscitaire. None of the participants had received education and
      training specifically on supporting fathers during newborn resuscitation.
      CONCLUSIONS: This is the first known study to specifically explore the
      experiences of healthcare professionals of the father's presence during newborn
      resuscitation. The findings suggest the need for more focused training about
      supporting fathers. There is also scope for service providers to consider ways in
      which fathers can be supported more readily during newborn resuscitation.

PMID- 23535759
TI  - Barrett esophagus and esophagojejunal anastomotic stenosis as complications of
      esophagogastric disconnection in children with esophageal atresia.
AB  - Total esophagogastric disconnection (TED) is an alternative surgical procedure in
      resistant gastroesophageal reflux disease. We report 2 severe, not yet described
      long-term complications of TED occurring in 4 children with a history of
      esophageal atresia. Three children presented with stenosis of the esophagojejunal
      anastomosis 5 months to 9 years after TED, requiring repeated dilations
      associated with mitomycin C application in one of them. Barrett esophagus was
      observed in 3 children 8 to 9 years after TED. Careful long-term clinical and
      endoscopic follow-up of children who underwent TED is required.

PMID- 23535760
TI  - Absence of effect of nasal continuous positive airway pressure on the esophageal
      phase of nutritive swallowing in newborn lambs.
AB  - OBJECTIVES: It is presently recommended that oral feeding be started in premature
      infants as soon as possible, often at an age at which nasal continuous positive
      airway pressure (nCPAP) is still required for ventilatory support. Our previous
      data showed that application of nCPAP up to 10 cmH2O in full-term lambs had no
      deleterious effect on cardiorespiratory safety, feeding efficiency, or on
      nutritive swallowing-breathing coordination. Besides fear of swallowing-breathing
      coordination disturbances, esophageal motility disruption by nCPAP could be a
      reason to delay oral feeding. To our knowledge, no study has focused on the
      effects of nCPAP on esophageal motility in the neonatal period. The aim of the
      present study was therefore to further assess the effects of nCPAP on oral
      feeding by assessing its effects on the esophageal phase of nutritive swallowing
      (nutritive esophagodeglutition). METHODS: Six full-term lambs, ages 2 to 3 days,
      underwent esophageal multichannel intraluminal impedance-pH monitoring. Lambs
      were bottle-fed under 2 randomized conditions, namely spontaneous breathing and
      nCPAP 6 cmH(2)O. RESULTS: Beyond confirmation of unaltered feeding efficiency,
      analysis of multiple variables measured by impedance monitoring revealed that
      nCPAP 6 does not alter nutritive esophagodeglutition in any way (nCPAP vs
      spontaneous breathing, P > 0.1 for all variables). CONCLUSIONS: offering further
      support to neonatologists pleading for initiation of oral feeding in infants
      still on nCPAP, the present results set the foundations for similar clinical
      studies in preterm human infants to confirm the absence of effects of nCPAP on
      nutritive swallowing.

PMID- 23535761
TI  - Oral prucalopride in children with functional constipation.
AB  - BACKGROUND AND OBJECTIVES: Prucalopride is a selective, high-affinity 5-HT4
      receptor agonist with gastrointestinal prokinetic activities. The aim of this
      study was to evaluate the pharmacokinetics, efficacy, safety, and tolerability of
      prucalopride oral solution in children, ages 4 years or older to 12 years or
      younger, with functional constipation. METHODS: A single oral dose of 0.03 mg/kg
      prucalopride was administered to 38 children to characterize prucalopride
      pharmacokinetics (NCT01674166). Thereafter, 37 children entered an open-label
      extension period in which 0.01 to 0.03 mg/kg of prucalopride was administered
      once per day for 8 weeks to investigate efficacy, safety, and tolerability
      (NCT01670669). RESULTS: Mean (standard deviation [SD]) Cmax, tmax, and
      AUCinfinity (area under the plasma concentration-time curve from time 0 to
      infinity) were 3.8 (0.6) ng/mL, 1.8 (0.9) hour, and 65.3 (10.6) ng . h . mL,
      respectively, with limited (16%) variability in Cmax and AUCinfinity. Mean (SD)
      t1/2 was 19.0 (3.1) hours. On average, mean (SD) renal clearance (0.25 [0.08] L .
      h . kg) accounted for 54% of the apparent total plasma clearance (0.46 [0.07] L .
      h . kg). The apparent volume of distribution was 12.6 (2.6) L/kg. Prucalopride
      treatment resulted in a mean bowel movement frequency of 6.8/week, normal stool
      consistency, and reduced frequency of fecal incontinence. During the 8-week
      extension, 70% of study participants had at least 1 adverse event (all but 1 of
      mild/moderate intensity, 19% considered related to prucalopride). No children
      discontinued prucalopride because of adverse events. CONCLUSIONS: The
      pharmacokinetic profile of a single dose of prucalopride oral solution (0.03 mg .
      kg . day) generally resembled the profile in adults (2-mg tablet) but reflected
      lower systemic exposure in children. Prucalopride treatment for 8 weeks
      demonstrated an apparent favorable efficacy and tolerability profile in children
      with functional constipation.

PMID- 23535762
TI  - Knowledge and practice styles of pediatricians in Saudi Arabia regarding
      childhood constipation.
AB  - OBJECTIVES: The aim of the present study was to evaluate knowledge and practice
      styles among medical providers working in 5 regions of Saudi Arabia regarding
      their approach to childhood constipation. METHODS: A survey of 850 pediatric
      providers (PPs) conducted in 5 regions of Saudi Arabia. PPs included pediatric
      specialists (PSs), pediatric consultants (PCs), general practitioners (GPs),
      family physicians (FPs), and pediatric gastroenterologists (PGs). They were asked
      anonymously about definition, causes, diagnosis, and management of constipation.
      Information about family concerns regarding constipation and the source of
      constipation-related information was also collected. RESULTS: A response rate of
      73% yielded 622 questionnaires. Among respondents, 61.2% were aware of the Rome
      definition of functional constipation. More pediatricians (PSs and PCs) than
      other physicians (GPs and FPs) reported the definition of constipation correctly
      (P > 0.05). Stool withholding was reported as the most common cause of
      constipation by 27% of pediatricians (PSs and PCs), 24% of other physicians (GPs
      and FPs), and 50% of PGs (P = 0.097). Rectal examination was performed by 39% of
      all PPs and 78.6% of PGs (P = 0.009). Pediatricians prescribed lactulose
      significantly more often than physicians (P = 0.001). Pediatricians recommended
      disimpaction before maintenance treatment significantly more than other
      physicians (P = 0.001). Twenty-three percent of families believed that
      constipation was caused by a stricture and 10% feared it was caused by a
      malignancy. CONCLUSIONS: Significant differences in knowledge and practice
      patterns exist regarding the approach to pediatric constipation. Identification
      of knowledge gaps may be useful to develop educational materials to improve
      proper diagnosis and treatment of childhood constipation.

PMID- 23535763
TI  - Predicting the severity of pediatric acute pancreatitis: are we there yet?

PMID- 23535764
TI  - Stop considering atopic dermatitis as an allergic disease.

PMID- 23535765
TI  - Probiotics for the prevention of necrotizing enterocolitis: not just which ones
      but also why?

PMID- 23535766
TI  - Efficacy of different probiotic combinations on death and necrotizing
      enterocolitis in a premature rat model.
AB  - OBJECTIVE: The aim of the present study was to investigate the most effective
      probiotic combinations to prevent death and necrotizing enterocolitis (NEC) in a
      premature rat model. METHODS: One hundred fifty-eight premature Sprague-Dawley
      premature rats were enrolled. Probiotic strains Bifidobacterium bifidum, B
      longum, Lactobacillus acidophilus, L plantarum, and B breve were fed as a single
      strain or mixture with 2 or 3 strains for a total of 9 study groups; control
      groups received no exogenous probiotic supplement. Fecal samples were collected
      for 72 hours to detect probiotic strains and pathologic strains by real-time
      polymerase chain reaction. Colony counts of probiotic strains Escherichia coli
      and Klebsiella were compared between groups before and after 36 hours of the
      study period. The incidence of death and NEC were compared via Fisher exact test
      between groups. RESULTS: The results demonstrated that L plantarum alone (P =
      0.0026) and B bifidum with B longum together (P = 0.0017) were more effective in
      reducing NEC as compared with the control group. All of the study groups except B
      breve and B bifidum with B breve definitely prevented death compared with
      controls. B bifidum and B longum together had significantly lower mortality than
      the control group (P < 0.0001). Colony counts of E coli and Klebsiella in stool
      samples were significantly decreased in the B bifidum, B longum, and L plantarum
      group compared with the other study and control groups after 36 hours.
      CONCLUSIONS: Administration of a mixture of probiotic strains with B bifidum and
      B longum was most effective in preventing death and NEC in this animal model, and
      these observations provide an evidence-based strategy for designing further
      neonatal clinical trials.

PMID- 23535767
TI  - Chemical insight into electroforming of resistive switching manganite
      heterostructures.
AB  - We have investigated the role of the electroforming process in the establishment
      of resistive switching behaviour for Pt/Ti/Pr0.5Ca0.5MnO3/SrRuO3 layered
      heterostructures (Pt/Ti/PCMO/SRO) acting as non-volatile Resistance Random Access
      Memories (RRAMs). Electron spectroscopy measurements demonstrate that the higher
      resistance state resulting from electroforming of as-prepared devices is strictly
      correlated with the oxidation of the top electrode Ti layer through field-induced
      electromigration of oxygen ions. Conversely, PCMO exhibits oxygen depletion and
      downward change of the chemical potential for both resistive states. Impedance
      spectroscopy analysis, supported by the detailed knowledge of these effects,
      provides an accurate model description of the device resistive behaviour. The
      main contributions to the change of resistance from the as-prepared (low
      resistance) to the electroformed (high resistance) states are respectively due to
      reduced PCMO at the boundary with the Ti electrode and to the formation of an
      anisotropic n-p junction between the Ti and the PCMO layers.

PMID- 23535769
TI  - Heart failure, comorbidities, and polypharmacy among elderly nursing home
      residents.
AB  - INTRODUCTION: Heart failure (HF) in the elderly is frequently associated with
      limited therapeutic options and may cause severe complications. Unfortunately,
      these patients are often excluded from clinical trials. OBJECTIVES: The aim of
      the study was to determine the relationship between HF, coexisting diseases, and
      use of medications in patients of advanced age living in nursing homes. PATIENTS
      AND METHODS: The study group included 79 women and 21 men between 65 and 102
      years of age living in 2 nursing homes. Information about the health status of
      patients was gathered from history and medical records. We conducted a physical
      examination and, in eligible cases, also an orthostatic test. Comorbidity was
      assessed using the age-adjusted Charlson comorbidity index (ACCI). RESULTS: The
      prevalence of HF was 26%. The number of chronic diseases coexisting with HF was
      remarkably higher than the number of diseases among patients without HF (median,
      6 [0-11] vs. 3 [0-8]; P <0.0001). The ACCI was also higher in the HF group
      compared with patients without HF (median, 7 [5-12] vs. 5.5 [2-9]; P <0.0001).
      Patients with HF took significantly more medications, although HF was treated
      according to the current guidelines in less than half of the cases. CONCLUSIONS:
      Our data revealed that HF is associated with significant morbidity and
      polypharmacy. There is a need for further research that would guide therapy of HF
      in elderly patients with limited life expectancy and multiple comorbidities as
      inhabitants of nursing homes. Nonetheless, the current treatment of nursing home
      patients with HF seems to be suboptimal.

PMID- 23535768
TI  - Structure and RNA-binding properties of the bacterial LSm protein Hfq.
AB  - Over the past years, small non-coding RNAs (sRNAs) emerged as important
      modulators of gene expression in bacteria. Guided by partial sequence
      complementarity, these sRNAs interact with target mRNAs and eventually affect
      transcript stability and translation. The physiological function of sRNAs depends
      on the protein Hfq, which binds sRNAs in the cell and promotes the interaction
      with their mRNA targets. This important physiological function of Hfq as a
      central hub of sRNA-mediated regulation made it one of the most intensely studied
      proteins in bacteria. Recently, a new model for sRNA binding by Hfq has been
      proposed that involves the direct recognition of the sRNA 3' end and interactions
      of the sRNA body with the lateral RNA-binding surface of Hfq. This review
      summarizes the current understanding of the RNA binding properties of Hfq and its
      (s)RNA complexes. Moreover, the implications of the new binding model for sRNA
      mediated regulation are discussed.

PMID- 23535770
TI  - Molecular characterization of begomoviruses and DNA satellites associated with
      okra leaf curl disease in Cameroon.
AB  - Okra leaf curl disease (OLCD) is the most important viral disease of okra in West
      Africa. In this study, a complex of begomoviruses and associated DNA satellites
      were identified in symptomatic okra plants from southwestern Cameroon. Sequence
      analyses showed that two of the plants (Lik1 and Njo5) were infected with a
      begomovirus being a recombinant of cotton leaf curl Gezira virus (CLCuGeV) and
      okra yellow crinkle virus (OYCrV). The recombinant genome shared highest
      nucleotide identity with isolates of CLCuGeV at 87.8% and is therefore considered
      to be member of a new begomovirus species, Okra leaf curl Cameroon virus
      (OLCuCMV). One plant (Mue5) was infected by a begomovirus with 95.8% nucleotide
      identy to CLCuGeV, while in the plants Lik1, Mue1 and Njo5, a begomovirus was
      identified showing highest nucleotide identity at 93.7% with OYCrV. The
      nucleotide comparisons and phylogenetic analyses suggest that these isolates
      represent new Cameroonian strains of CLCuGeV and OYCrV (CLCuGeV-CM and OYCrV-CM).
      Mixed infection of OLCuCMV and OYCrV-CM was found in two of the plants. A
      betasatellite and two divergent alphasatellites were also associated with the
      begomoviruses. The betasatellite was identified as cotton leaf curl Gezira
      betasatellite (CLCuGeB) with the highest nucleotide identity at 93.3% to other
      African isolates of CLCuGeB. The alphasatellites, herein named Alpha-1 and Alpha
      2, shared 97.3% and 95.2% identity, respectively, with cotton leaf curl Gezira
      alphasatellite (CLCuGeA) and okra leaf curl Burkina Faso alphasatellite
      (OLCuBFA). These collective results emphasize the extent of diversity among okra
      infecting begomovirus-satellite complexes in western Africa.

PMID- 23535771
TI  - Molecular systematics of Allium subgenus Amerallium (Amaryllidaceae) in North
      America.
AB  - PREMISE OF THE STUDY: Early plant taxonomists formed hypotheses about
      relationships among taxa based on characters such as morphology, anatomy,
      phytochemistry, ecology, and geography. Modern molecular systematic methods,
      based on DNA sequence variation, augment early methods and provide an additional
      line of evidence by which to evaluate taxonomic hypotheses. In North America
      north of Mexico, wild onions (Allium, Amaryllidaceae) are represented by 84
      native species, 81 of which belong to subgenus Amerallium. On the basis of
      morphology, these species have been divided into eight informal taxonomic
      "alliances" hypothesized to represent shared evolutionary history among species.
      The main aim of this research was to test the monophyly of the alliances with
      molecular phylogenetic methods. METHODS: We sampled 74 Amerallium species north
      of Mexico and two Mexican endemics and constructed a molecular phylogeny of
      subgenus Amerallium in North America based on predominantly noncoding sequences
      from two nuclear ribosomal RNA regions (ITS and ETS) and two plastid regions
      (trnL-F and rpL32-trnL). KEY RESULTS: Most clades are well supported in analyses
      of nuclear data and when nuclear and plastid data are combined. However, the
      plastid data alone did not produce a well-resolved or well-supported tree.
      Morphological alliances were sometimes congruent with groups recovered in the
      molecular phylogeny, but strict monophyly was observed in only three of eight
      alliances. CONCLUSIONS: We propose an infrageneric classification that recognizes
      two sections in New World Amerallium. Because there is substantial incongruence
      between morphological and molecular groups, we advocate retaining informal
      alliances rather than adopting formal subsections until further morphological and
      molecular analyses can be carried out.

PMID- 23535772
TI  - An early origin of secondary growth: Franhueberia gerriennei gen. et sp. nov.
      from the Lower Devonian of Gaspe (Quebec, Canada).
AB  - PREMISE OF THE STUDY: Secondary xylem (wood) produced by a vascular cambium
      supports increased plant size and underpins the most successful model of
      arborescence among tracheophytes. Woody plants established the extensive forest
      ecosystems that dramatically changed the Earth's biosphere. Secondary growth
      evolved in several lineages in the Devonian, but only two occurrences have been
      reported previously from the Early Devonian. The evolutionary history and
      phylogeny of wood production are poorly understood, and Early Devonian plants are
      key to illuminating them. METHODS: A fossil plant preserved anatomically by
      cellular permineralization in the Lower Devonian (Emsian, ca. 400-395 million
      years old) Battery Point Formation of Gaspe Bay (Quebec, Canada) is described
      using the cellulose acetate peel technique. KEY RESULTS: The plant, Franhueberia
      gerriennei Hoffman et Tomescu gen. et sp. nov., is a basal euphyllophyte with a
      centrarch protostele and metaxylem tracheids with circular and oval to
      scalariform bordered multiaperturate pits (P-type tracheids). The outer layers of
      xylem, consisting of larger-diameter P-type tracheids, exhibit the features
      diagnostic of secondary xylem: radial files of tracheids, multiplicative
      divisions, and a combination of axial and radial components. CONCLUSIONS:
      Franhueberia is one of the three oldest euphyllophytes exhibiting secondary
      growth documented in the Early Devonian. Within the euphyllophyte clade, these
      plants represent basal lineages that predate the evolution of stem-leaf-root
      organography and indicate that underlying mechanisms for secondary growth became
      part of the euphyllophyte developmental toolkit very early in the clade's
      evolution.

PMID- 23535773
TI  - Phylogenetic relationships of the mycoheterotrophic genus Voyria and the
      implications for the biogeographic history of Gentianaceae.
AB  - PREMISE OF THE STUDY: The angiosperm family Gentianaceae comprises over 1700
      species in 91 genera. Gentianaceae are distributed worldwide, but most species
      occur in temperate zones. Phylogenetic studies demonstrate that the family
      consists of six monophyletic tribes. However, the phylogenetic position of the
      mycoheterotrophic genus Voyria, with a remarkable trans-Atlantic distribution,
      remained unknown. METHODS: We used nuclear ITS and 18S rDNA and mitochondrial
      apt1 and matR data to infer the phylogenetic position of Voyria in Gentianaceae.
      In addition, with Bayesian relaxed molecular clock analyses we obtained age
      estimates for the diversification of Voyria and Gentianaceae in general and used
      these results to reconstruct the ancestral areas associated with the early
      diversification events in Gentianaceae. KEY RESULTS: Our results demonstrate that
      Voyria is an early diverging lineage within Gentianaceae with no close
      relationships to other mycoheterotrophic Gentianaceae lineages. Voyria originated
      in the neotropics during the Early Eocene but only reached its current
      transoceanic distribution around the end of the Oligocene. The neotropics were an
      important area for the early diversification events in Gentianaceae, most of
      which occurred during the Eocene. CONCLUSIONS: Voyria is an old, phylogenetically
      isolated lineage within Gentianaceae, and the current distribution of the genus
      is indicative of the ancestral area in which the early diversification events of
      Gentianaceae occurred. In parallel with many other pantropical families, our
      results suggest that migration of tropical taxa through Laurasia during the Early
      Eocene has played an important role in shaping the current global distribution of
      Gentianaceae.

PMID- 23535774
TI  - Successful treatment of a spontaneous rupture of the left external iliac vein in
      a man.
AB  - Spontaneous rupture of the external iliac vein associated with a May-Thurner
      syndrome is infrequent, particularly in men. We report a case of previously
      healthy 73-year-old man with a left iliac vein thrombosis, who presented a large
      lower left abdominal hematoma of sudden-unset. Emergent laparotomy revealed a 3
      cm longitudinal tear in the left external iliac vein, which was repaired
      primarily. Patient's recovery was uneventful. Possible etiological factors have
      been identified as venous hypertension due to iliac vein thrombosis associated
      with Cockett syndrome, as well as inflammatory venous wall. Some other estrogenic
      factors could explain female preponderance of the event.

PMID- 23535775
TI  - A vascular laboratory protocol for improving and managing after-hours suspected
      acute deep venous thrombosis.
AB  - This study reviews the clinical and workforce impact of a suggested protocol
      designed for the management of suspected acute deep venous thrombosis (DVT) in
      patients seen after standard vascular laboratory business hours. The protocol
      included the use of Wells score, D-dimer and a single dose of therapeutic
      anticoagulant to defer venous duplex ultrasound (VDU) testing until routine
      business hours unless contraindicated. Information was collected on medical
      history, physical exam and the timing of any diagnostic studies and treatment
      provided. Over 15% of studies done after-hours were deemed unnecessary by our
      protocol and in every individual the results were negative for an acute DVT.
      There were no adverse events from a one-time dose of anticoagulant. Limiting
      emergency VDU coverage to evaluate for acute DVT based on a management protocol
      can eliminate unnecessary after-hours VDU testing without having a negative
      impact on patient care. 

PMID- 23535776
TI  - Aspirin usage is associated with improved prosthetic infrainguinal bypass graft
      patency.
AB  - The American Heart Association recommends that, unless contraindicated, all
      patients undergoing surgical revascularization for critical limb ischemia should
      be placed postoperatively on antiplatelet therapy and remain on it indefinitely.
      The goal of this study was to evaluate if preoperative use of aspirin was
      associated with improved bypass grafting patency rates and limb salvage. We
      performed a four-year, retrospective review of one center's experience with open
      infra-inguinal bypass. We examined the effect pre- and postoperative usage of
      antiatherosclerotic agents (i.e. aspirin, statin, etc.) have on graft outcomes
      such as two-year secondary patency, stenosis and limb salvage via univariate
      Kaplan-Meir survival curve analysis and multiple regression analysis. Our cohort
      included 165 bypasses in individuals with multiple co-morbidities. The most
      frequent indication was critical limb ischemia (79%) and most bypasses crossed
      the knee (63%). Pre- and postoperative aspirin usage was associated with
      increased two-year secondary prosthetic graft patency over control (preoperative:
      78% versus 44%, P < 0.002 and postoperative: 72% versus 50%, P < 0.01).
      Preoperative aspirin usage was associated with an improvement in the rate of
      amputation (odds ratio [OR] = 0.44 [95% CI 0.198-0.997]) and stenosis (OR = 0.45
      [95% CI 0.217-0.956]). Medications commonly prescribed for atherosclerosis such
      as aspirin are associated with a significant patency benefit when administered
      pre- and postoperatively. In a population undergoing infrainguinal bypass with
      prosthetic graft for predominantly critical limb ischemia, medical optimization
      should include both pre- and postoperative antiatherosclerotic drug regimens. 

PMID- 23535777
TI  - A concise approach to the spiroiminal fragment of marineosins.
AB  - A concise approach to the spiroiminal fragment of marineosins A and B is
      described. The key steps involve an acid-catalyzed N-acyliminium ion cyclization
      and a Vilsmeier-Haack type reaction with Tf2O.

PMID- 23535778
TI  - Conditioned contribution of peripheral cocaine actions to cocaine reward and
      cocaine-seeking.
AB  - Cocaine has actions in the peripheral nervous system that reliably precede--and
      thus predict--its soon-to-follow central rewarding effects. In cocaine
      experienced animals, the peripheral cocaine signal is relayed to the central
      nervous system, triggering excitatory input to the ventral tegmental origin of
      the mesocorticolimbic dopamine system, the system that mediates the rewarding
      effects of the drug. We used cocaine methiodide, a cocaine analog that does not
      cross the blood-brain barrier, to isolate the peripheral actions of cocaine and
      determine their central and behavioral effects in animals first trained to lever
      press for cocaine hydrochloride (the centrally acting and abused form of the
      drug). We first confirmed with fast-scan cyclic voltammetry that cocaine
      methiodide causes rapid dopamine release from dopamine terminals in cocaine
      hydrochloride-trained rats. We then compared the ability of cocaine hydrochloride
      and cocaine methiodide to establish conditioned place preferences in rats with
      self-administration experience. While cocaine hydrochloride established stronger
      place preferences, cocaine methiodide was also effective and its effectiveness
      increased (incubated) over weeks of cocaine abstinence. Cocaine self
      administration was extinguished when cocaine methiodide or saline was substituted
      for cocaine hydrochloride in the intravenous self-administration paradigm, but
      cocaine hydrochloride and cocaine methiodide each reinstated non-rewarded lever
      pressing after extinction. Rats extinguished by cocaine methiodide substitution
      showed weaker cocaine-induced reinstatement than rats extinguished by saline
      substitution. These findings suggest that the conditioned peripheral effects of
      cocaine can contribute significantly to cocaine-induced (but not stress-induced)
      cocaine craving, and also suggest the cocaine cue as an important target for cue
      exposure therapies for cocaine addiction.

PMID- 23535780
TI  - Hollow porous SiO2 nanocubes towards high-performance anodes for lithium-ion
      batteries.
AB  - The high theoretical capacity and low discharge potential of silicon have
      attracted much attention on Si-based anodes. Herein, hollow porous SiO2 nanocubes
      have been prepared via a two-step hard-template process and evaluated as
      electrode materials for lithium-ion batteries. The hollow porous SiO2 nanocubes
      exhibited a reversible capacity of 919 mAhg(-1) over 30 cycles. The reasonable
      property could be attributed to the unique hollow nanostructure with large volume
      interior and numerous crevices in the shell, which could accommodate the volume
      change and alleviate the structural strain during Li ions' insertion and
      extraction, as well as allow rapid access of Li ions during charge/discharge
      cycling. It is found that the formation of irreversible or reversible lithium
      silicates in the anodes determines the capacity of a deep-cycle battery, fast
      transportation of Li ions in hollow porous SiO2 nanocubes is beneficial to the
      formation of Li2O and Si, contributing to the high reversible capacity.

PMID- 23535781
TI  - TBI and aging.

PMID- 23535783
TI  - Traumatic encephalopathy: review and provisional research diagnostic criteria.
AB  - OBJECTIVES: To determine the frequency of neurobehavioral signs and symptoms
      reported in every published case of traumatic encephalopathy with a view toward
      the development of clinical diagnostic criteria with predictive validity.
      INTRODUCTION: Cases of persistent or progressive neurological or neurobehavioral
      change following exposure to one or more head injuries have been reported since
      1928. This condition is often referred to as traumatic encephalopathy (TE). To
      date, however, no diagnostic criteria have been advanced or accepted for the
      clinical diagnosis of TE. Provisional research diagnostic criteria are required
      not only for meaningful diagnosis but also to facilitate research to determine
      the epidemiology, etiology, course, prognosis, imaging and biomarkers,
      neuropathological features and potentially effective treatments of TE. METHODS:
      All 436 published cases of TE in all languages were reviewed. All symptoms and
      signs reported in these cases were classified and enumerated. RESULTS: Ninety
      seven cases met inclusion criteria based on sufficient documentation of the
      history and neurobehavioral examination. Provisional research diagnostic criteria
      for clinically probable and clinically possible TE were developed based on the
      most frequently reported clinical features. CONCLUSION: The provisional
      diagnostic criteria for TE presented here are the first published criteria for
      this condition based upon a systematic analysis of its clinical characteristics.
      This is the first a step toward scientifically derived consensus criteria, which
      are essential to accelerate progress in the investigation of this important
      condition.

PMID- 23535782
TI  - An exploration of clinical dementia phenotypes among individuals with and without
      traumatic brain injury.
AB  - OBJECTIVE: To characterize the clinical profiles of individuals with dementia who
      do and do not report a history of TBI. INTRODUCTION: Some evidence suggests that
      a history of traumatic brain injury (TBI) is associated with an increased risk of
      dementia later in life. The clinical features of dementia associated with TBI
      have not been well investigated. While there is some evidence that TBI is
      associated with increased risk of Alzheimer's disease (AD), there are also
      indications that dementia associated with TBI has prominent behavioral,
      affective, and motor symptoms, making it distinct from AD. METHODS: The current
      study involves secondary analysis of baseline data from the National Alzheimer's
      Coordinating Center (NACC) Uniform Data Set (UDS). RESULTS: Individuals with
      dementia who reported a history of TBI had higher fluency and verbal memory
      scores and later onset of decline, but they are on more medications, had worse
      cardiovascular and cerebrovascular health, were more likely to have received
      medical attention for depression, and were more likely to have a gait disorder,
      falls, and motor slowness. CONCLUSION: These findings suggest that dementia among
      individuals with a history of TBI may represent a unique clinical phenotype that
      is distinct from known dementia subtypes.

PMID- 23535779
TI  - Effects of repeated stress on excitatory drive of basal amygdala neurons in vivo.
AB  - Chronic stress leads to heightened affective behaviors, and can precipitate the
      emergence of depression and anxiety. These disorders are associated with
      increased amygdala activity. In animal models, chronic stress leads to increased
      amygdala-dependent behaviors, as well as hyperactivity of amygdala neurons.
      However, it is not known whether increased excitatory synaptic drive after
      chronic stress contributes to hyperactivity of basolateral amygdala (BLA;
      comprised of basal, lateral, and accessory basal nuclei) neurons. This study
      tested whether repeated stress causes an increase in excitatory drive of basal
      amygdala (BA) neurons in vivo, and whether this is correlated with an increase in
      the number of dendritic spines and a shift in dendritic distribution. Using in
      vivo intracellular recordings, this study found that repeated restraint stress
      caused an increase in the frequency of spontaneous excitatory synaptic events in
      vivo, which correlated with the number of dendritic spines in reconstructed
      neurons. Furthermore, parallel changes in the kinetics of the synaptic events and
      the distribution of spines indicated a more prominent functional contribution of
      synaptic inputs from across the dendritic tree. The shift in spine distribution
      across the dendritic tree was further confirmed with the examination of Golgi
      stained tissue. This abnormal physiological drive of BA neurons after repeated
      stress may contribute to heightened affective responses after chronic stress. A
      reduction in the impact of excitatory drive in the BA may therefore be a
      potential treatment for the harmful effects of chronic stress in psychiatric
      disorders. 

PMID- 23535784
TI  - Mortality of elderly individuals with TBI in the first 5 years following injury.
AB  - INTRODUCTION: Although there has been a decline in the incidence of TBI in the
      general population, the rate of TBI in older adults has increased. Increased age
      has been long recognized as a predictor of worse outcomes after TBI. Despite the
      growing number of TBI in the elderly, our understanding of the long-term
      consequences of TBI is quite limited. METHODS: Chart review; individuals 55 years
      and older, who completed inpatient acute rehabilitation during the period 2003
      2009 and who died one to four years after injury, were compared to matched
      patients who did not die. RESULTS: There were a significantly higher proportion
      of deceased subjects with a diagnosis of Abnormality of Gait (53%), respiratory
      medications at admission (32%) and discharge (17%). Deceased participants were
      more likely to be prescribed diabetes medication at discharge (35%) while
      controls were more likely to be prescribed cholesterol-lowering medications (27%)
      at admission. Deceased patients were discharged with significantly more
      medications, CONCLUSIONS: The results suggest the need for medical and lifestyle
      interventions for selected elderly TBI patients. The factors related to death
      following TBI in the elderly are in need of more research.

PMID- 23535785
TI  - Inpatient rehabilitation for traumatic brain injury: the influence of age on
      treatments and outcomes.
AB  - BACKGROUND: Elderly persons with traumatic brain injury (TBI) are increasingly
      admitted to inpatient rehabilitation, but we have limited knowledge of their
      characteristics, the treatments they receive, and their short-term and medium
      term outcomes. This study explored these issues by means of comparisons between
      age groups. METHODS: Data on 1419 patients admitted to 9 inpatient rehabilitation
      facilities for initial rehabilitation after TBI were collected by means of (1)
      abstraction from medical records; (2) point-of care forms completed by therapists
      after each treatment session; and (3) interviews at 3 months and 9 months after
      discharge, conducted with the patient or a proxy. RESULTS: Elderly persons (65 or
      older) had a lower brain injury severity, and a shorter length of stay (LOS) in
      acute care. During rehabilitation, they received fewer hours of therapy, due to a
      shorter LOS and fewer hours of treatment per day, especially from psychology and
      therapeutic recreation. They regained less functional ability during and after
      inpatient rehabilitation, and had a very high mortality rate. CONCLUSIONS:
      Elderly people can be rehabilitated successfully, and discharged back to the
      community. The treatment therapists deliver, and issues surrounding high
      mortality need further research.

PMID- 23535787
TI  - Psychosocial functioning in older adults with traumatic brain injury.
AB  - OBJECTIVE: The purpose of this paper is to review the literature on psychosocial
      outcomes in older adults with TBI and identify factors associated with positive
      outcomes in this population. INTRODUCTION: Rates of TBI in older adults have
      increased in recent years. Little is known regarding the factors and cohort
      specific characteristics that contribute to long-term healthy psychosocial
      functioning in this population. METHODS: Review of literature. RESULTS: A
      multitude of factors that impact psychosocial outcomes are discussed, including
      injury characteristics, individual characteristics, aging and cohort issues, and
      external environmental factors. CONCLUSIONS: There is limited research examining
      psychosocial functioning in older adults who have sustained a TBI.
      Recommendations to guide clinical care and future research are provided.

PMID- 23535786
TI  - Bi-factor analyses of the Brief Test of Adult Cognition by Telephone.
AB  - BACKGROUND: Telephone cognitive batteries are useful for large-scale screening
      and epidemiological studies, but their brevity and lack of content depth may
      cause psychometric limitations that hinder their utility. OBJECTIVE: The current
      study addressed some of these limitations by rescaling the Brief Test of Adult
      Cognition by Telephone (BTACT; Tun & Lachman, 2006) using modern psychometric
      methods. METHODS: Archival data were obtained from a national sample of 4,212 28
      to 84-year-old volunteers in the National Survey of Midlife Development in the
      United States (Ryff et al., 2007) Cognitive Project (Ryff & Lachman, 2007). We
      fit a bi-factor model to a combination of item-level, subscale-level, and scale
      level data. RESULTS: The best fitting model contained a general factor and
      secondary factors capturing test-specific method effects or residual correlations
      for Number Series, Red/Green Test, and the Rey Auditory Verbal Learning Test.
      Factor scores generated from this model were compared with conventional BTACT
      scores. Important score differences (i.e., >0.3 standard deviation units) were
      found in 28% of the sample. The bi-factor scores demonstrated slightly superior
      validity than conventional BTACT scores when judged against a number of clinical
      and demographic criterion variables. CONCLUSIONS: Modern psychometric approaches
      to scoring the BTACT have the benefit of linear scaling and a modest criterion
      validity advantage.

PMID- 23535788
TI  - Examining and reporting the status of statistical assumptions in
      neuropsychological research: a misbegotten ethical obligation?
AB  - The ethical responsibilities within clinical practice are ubiquitous. Yet,
      several aspects comprising the clinical neuropsychologist's role, although
      carrying equal ethical 'weight, ' may be relegated to a lesser value and are
      considered irregularly. This paper is of the position that statistical
      assumptions are arbitrarily and unpredictably reported in research. However,
      violating statistical assumptions can often yield untenable results, rendering
      the inferences based on the primary analysis equally precarious. Just as
      clinicians are enjoined by their respective professional organizations to abide
      scrupulously by ethical principles in clinical practice, neuropsychologists
      should be equally careful over such important matters in research. Consistent
      examination (and rectification when needed) and reporting of the status of
      statistical assumptions will help to not only broaden and maintain the ambitions
      of sound ethical practice but, ultimately ensure optimal patient care.

PMID- 23535789
TI  - Comparative neuroimaging in children with cerebral palsy using fMRI and a novel
      EEG-based brain mapping during a motor task--a preliminary investigation.
AB  - PURPOSE: The purpose of this study was to compare topographical maps using a
      novel EEG-based brain mapping system with fMRI in normal and children with
      cerebral palsy (CP) during a grasping motor task. METHOD: A normal child (mean +/
      SD = 13 +/- 0 yrs) and four children with CP (mean +/- SD = 10.25 +/- 2.86 yrs)
      were recruited from a local community school and medical center. A novel EEG
      based brain mapping system with 30 scalp sites (an extension of the 10-20 system)
      and a 3T MR scanner were used to observe cortical activation patterns during a
      grasping motor task. DESIGN: Descriptive analysis. RESULTS: In the EEG brain
      mapping data, the sensorimotor cortex (SMC) and inferior parietal cortex (IPC)
      were activated in all of the children. The children with CP showed additional
      activation areas in the premotor cortex (PMC), superior parietal cortex (SPC),
      and prefrontal cortex (PFC). In the fMRI brain mapping data, SMC activation was
      observed in all of the children, and the children with CP showed additional
      activation areas in the PMC and primary somatosensory cortex (PSC). DISCUSSION:
      The EEG-based topographical maps were equivalent to the maps obtained from fMRI
      during the grasping motor task. The results indicate that our novel EEG-based
      brain mapping system is useful for probing cortical activation patterns in normal
      children and children with CP.

PMID- 23535790
TI  - Effects of functional movement strength training on strength, muscle size,
      kinematics, and motor function in cerebral palsy: a 3-month follow-up.
AB  - We investigated the long-term effects of comprehensive hand repetitive intensive
      strengthening training (CHRIST) on strength, morphological muscle size,
      kinematics, and associated motor functional changes in children with cerebral
      palsy (CP). Ten children (5 boys, 5 girls; age range, 6-11 years, mean age, 8.6
      years) participated in the study. The children were classified according to the
      Manual Ability Classification System: 5 were Level II, 2 were Level III, and 3
      were Level IV. Quantitative biomechanical measurements were performed to
      determine muscle strength, muscle size, kinematics (normalized jerk score), and
      motor function using a dynamometer, ultrasound, Vicon motion analysis, and
      standardized clinical tests (Quality of Upper Extremity Skills Test, Jebsen
      Taylor Hand Function Test, Functional Independence Measure, and Pediatric Motor
      Activity Log), respectively. Muscle strength, muscle size, kinematics, and motor
      function significantly improved after a 10-week intervention (3 times a week),
      and the long-term effects remained even at the 3-month follow-up. In conclusion,
      this is the first study highlighting the long-term efficacy of upper extremity
      strength training using the novel CHRIST system in children with CP, which will
      potentially open up new horizons for effective management in pediatric
      neurorehabilitation.

PMID- 23535791
TI  - Attention training in rehabilitation of children with developmental stuttering.
AB  - BACKGROUND: Attention and executive function play an important role in fluent
      speaking. The aim of the present study is to evaluate effect of attention
      training in rehabilitation of stuttering. METHOD: In this random clinical trial
      30 children with developmental stuttering participate in a random allocation
      sampling in case or control group. In case group, we trained patient with
      NEurocognitive Joyful Attentive Training Intervention (NEJATI) in 12 sessions.
      Riley Stuttering severity instrument-3 (SSI-3), Wisconsin Card Sorting Test
      (WCST), and Stroop Color Word Test (SCWT) are used for evaluation of executive
      function before and after intervention. Dependent T-Test was used for analysis.
      RESULTS: Comparing case group before and after intervention showed a significant
      enhancement in executive function and reduced stuttering severity. CONCLUSION:
      Attention training propose as a non lingual method of language and speech
      rehabilitation in developmental stuttering.

PMID- 23535792
TI  - Recovery of an injured corticospinal tract and an injured corticoreticular
      pathway in a patient with intracerebral hemorrhage.
AB  - The main function of the corticospinal tract (CST) is control of the distal
      musculature used for fine movements, in contrast, the corticoreticular pathway
      (CRP) innervates the proximal and axial musculature. We report on a patient with
      an intracerebral hemorrhage (ICH) who showed recovery of an injured CST and an
      injured CRP by diffusion tensor tractography (DTT). The patient, a 38-year-old
      man, presented with severe paralysis of the right upper and lower extremities due
      to a spontaneous ICH in the left corona radiata and basal ganglia. When he
      started rehabilitation at 3 weeks after onset, he showed more severe weakness in
      the proximal joints (shoulder and hip joints) than distal joints (hand and ankle
      joints). This proximal weakness improved rapidly in parallel with distal weakness
      over 3 weeks of rehabilitation. DTT performed at 3 and 6 weeks post-ICH revealed
      that a thin left CST observed at 3 weeks thickened at 6 weeks, and that a
      discontinuation of the left CRP at the midbrain level at 3 weeks was restored at
      6 weeks. In addition, the track volumes of the left CST and CRP increased from
      221 and 244 at 3 weeks to 725 and 625 at 6 weeks. In conclusion, we demonstrated
      the recovery of an injured CST and an injured CRP in a patient with ICH.

PMID- 23535793
TI  - Motor function-related maladaptive plasticity in stroke: a review.
AB  - Brain plasticity can be classified as adaptive and maladaptive. Maladaptive
      plasticity indicates hindered functional recovery or the development of an
      unwanted symptom. Although a considerable amount is known about adaptive
      plasticity in stroke, relatively little is known of maladaptive plasticity. In
      the current study, previous studies on motor function-related maladaptive
      plasticity in stroke are reviewed in terms of compensatory movement pattern
      (CMP), delayed-onset involuntary abnormal movements (IAMs), and the ipsilateral
      motor pathway as a motor recovery mechanism. For successful stroke
      rehabilitation, it is important that the characteristics of maladaptive
      plasticity are accurately recognized. However, there is a lack of definitive
      evidence regarding the recognition of motor function-related maladaptive
      plasticity, although it seems that each of the three above-mentioned topics are
      involved. As for CMP, patients with a good neurological state as much as having a
      normal movement pattern, should be considered to have maladaptive plasticity, and
      in terms of the ipsilateral motor pathway, patients with bilateral innervations
      can be considered to have maladaptive plasticity. On the other hand, IAMs due to
      delayed neuronal degeneration should be ruled out in patients with delayed-onset
      IAMs. Therefore, for the accurate recognition of motor function-related
      maladaptive plasticity in stroke, a thorough evaluation of neurological state
      using brain mapping techniques is necessary, and subsequently, the prevention or
      intensive management of maladaptive plasticity is needed.

PMID- 23535794
TI  - Effects of the Elastic Walking Band on gait in stroke patients.
AB  - This study investigated how stroke patients improve the walking patterns by using
      the Elastic Walking Band, which was included with a long elastic band and four
      pierced plastics as fixed points. Fifteen patients with stroke were recruited.
      Participants were nine males and six females. Gait parameters were measured with
      the GAITRite system to analyze the spatial and temporal parameters of walking by
      stroke patients. The Elastic Walking Band had no significance in cadence, swing
      time and stance on both limbs. However, the Elastic Walking Band significantly
      improved velocity in stroke patients. Furthermore, there was a significant
      difference in step length of the less-affected limb between the two conditions,
      but no significant difference in the affected side. When the patients walked with
      the Elastic Walking Band, affected and less-affected stride length were also
      significantly increased as compared with barefoot walking. There were significant
      differences of velocity, less-affected step length, both stride length between
      walking with and without the Elastic Walking Band. Consequently, the Elastic
      Walking Band can be used as an assistive walking device that is lighter and less
      expensive for stroke patient gait training in the clinic.

PMID- 23535795
TI  - Correlation of trunk impairment with balance in patients with chronic stroke.
AB  - OBJECTIVE: To evaluate the correlation between the trunk impairment and balance
      in patients with chronic stroke. METHODS: Thirty subjects with chronic stroke
      participated in the study. The subjects were evaluated with the trunk impairment
      scale (TIS) and Tinetti balance scale (TBS). RESULT: Spearman's correlation
      showed highly significant correlation between TIS and TBS scores (rho = 0.911).
      CONCLUSION: The study reveals that the trunk impairment and balance in subjects
      with stroke are positively correlated with each other.

PMID- 23535796
TI  - Effects of aerobic cycling training on cardiovascular fitness and heart rate
      recovery in patients with chronic stroke.
AB  - OBJECTIVE: Using heart rate recovery (HRR) after exercise as an index of
      autonomic function, we evaluate the effects of aerobic cycling training on HRR
      and cardiovascular fitness (peak VO2) in chronic stroke patients and investigate
      the relationship between changes in HRR and those in peak VO2. METHODS: 128
      participants with chronic stroke were randomized to a 12-week (5*/week)
      progressive aerobic cycling training group (n = 65) or a control group (n = 63).
      Peak VO2, muscle strength, 6-minute walking distance (6MWD) and HRR were measured
      before and after the intervention. RESULTS: Cycling training leads to significant
      increase in peak VO2, HRR, muscle strength and 6MWD. In the cycling group,
      percent changes in peak VO2 were positively associated with those in paretic and
      nonparetic muscle strength and HRR. Linear regression revealed that percent
      increases in peak VO2 were significantly correlated with percent changes in HRR
      when controlling for pre-peak VO2, age, gender, duration since stroke and
      improved muscle strength. CONCLUSION: Aerobic cycling training can favorably
      modify HRR in stroke survivors. Rapid HRR, as an indicator of enhanced autonomic
      function, is useful for predicting gains in cardiovascular fitness. These
      findings indicate the underlying importance of autonomic modulation on
      cardiovascular adaptations to stroke exercise rehabilitation.

PMID- 23535797
TI  - Circadian and homeostatic changes of sleep-wake and quality of life in stroke:
      implications for neurorehabilitation.
AB  - The present study aimed to assess changes in the circadian and homeostatic
      control of the sleep-wake pattern in stroke patients and correlations with
      quality of life. Participants were 22 patients (55 +/- 12 years) and 24 healthy
      subjects (57 +/- 11 years). Instruments used were: the Pittsburgh Sleep Quality
      Index, SF-36 Questionnaire and Actigraphy. Data were analyzed by Mann-Whitney
      test and Spearman's correlation. Results identified a significant difference in
      sleep quality and quality of life between patients and healthy subjects, with
      patients on average exhibiting poor sleep quality (patients: 8.4 +/- 3.4; healthy
      subjects: 6.2 +/- 2.5; p = 0.0001) and low quality of life scores (p < 0.001).
      Correlation analysis detected an association between circadian variables (total
      activity, start and finish times of activity) and quality of life (p < 0.001).
      Associations between homeostatic variables (sleep duration, latency and
      efficiency) and quality of life were also significant (p < 0.001). In conclusion,
      results in this study showed compromised sleep quality and quality of life in the
      patients evaluated, associated with circadian and homeostatic alterations. This
      suggests that complaints regarding poor sleep quality be taken into consideration
      when planning the rehabilitation of stroke patients.

PMID- 23535798
TI  - Temporal recovery and predictors of upper limb dexterity in the first year of
      stroke: a prospective study of patients admitted to a rehabilitation centre.
AB  - OBJECTIVE: To document temporal recovery of upper extremity dexterity and
      establish predictors of limb dexterity in a cohort of stroke patients in the
      first year after stroke. DESIGN: Prospective cohort study. SUBJECTS: One hundred
      patients with a first-ever ischemic stroke admitted to a rehabilitation centre.
      METHODS: Assessment of upper extremity dexterity, motor power and selfcare
      function using the Motor Assessment Scale (MAS), Upper Extremity Motor Index
      (UEMI) and Modified Barthel Index (MBI) respectively. RESULTS: Eighteen percent,
      25.5% and 31.6% of patients recovered limb dexterity at 3, 6 and 12 months after
      stroke respectively. Patients who recovered dexterity late (>=6 months after
      stroke) were significantly younger with lower rehabilitation admission UEMI
      scores than those who recovered dexterity early. The UEMI score was the most
      significant correlate of limb dexterity at all follow up periods. Recovery of
      limb dexterity at 12 months was predicted by UEMI (OR1.54, 95% CI 1.13-2.10) and
      MBI (OR 1.03, 95% CI 1.00-1.07) scores on admission to rehabilitation.
      CONCLUSIONS: In this study, 31.6% of patients recovered upper extremity dexterity
      at 12 months after stroke. Although late recovery of dexterity occurs only in a
      small proportion of patients, this finding is still pertinent given the
      significant impact of dexterity on upper limb and selfcare function.

PMID- 23535799
TI  - Alleviating psychosocial issues for individuals with communication impairments
      and their families following stroke: a case series of interdisciplinary
      assessment and intervention.
AB  - INTRODUCTION: A high incidence of depression following a stroke has been
      reported. Many studies exclude those with communication impairments. However,
      there is an increased risk of psychosocial issues for individuals with
      communication difficulties. Psychosocial issues have a significant impact on the
      individual and their families. There is very limited research in this area.
      METHODS: A retrospective case review of the assessment and intervention with
      three individuals with significant communication difficulties following stroke
      was completed. Key interdisciplinary intervention factors were identified.
      RESULTS: Psychosocial issues were identified in all three cases. The assessment
      of cognitive difficulties, interdisciplinary intervention targeting communication
      between family members, facilitation of emotional expression and liaison with
      appropriate community services were identified as key interventions. These
      interventions targeted at psychosocial issues resulted in a positive outcome for
      the individuals and their family. DISCUSSION AND CONCLUSION: Psychosocial issues
      are prevalent in individuals and their families with significant communication
      impairments following stroke. Clinically, these issues may be overlooked. The
      complexity of working with individuals with cognitive and communication
      impairments also contributes to poor identification of psychosocial issues. This
      case series clearly highlights that intervening at the psychosocial level through
      interdisciplinary working can facilitate meaningful outcomes for the individual
      and their family.

PMID- 23535800
TI  - Effect of computer-based cognitive rehabilitation (CBCR) for people with stroke:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: We conducted a systematic review and meta-analysis to identify the
      effect of computer-based cognitive rehabilitation (CBCR) on improving cognitive
      functions in patients with stroke. METHODS: Researchers performed a literature
      search using computerized databases such as the Cochrane Database, EBSCO
      (CINAHL), PsycINFO, PubMed and Web of Science. The following keywords were used:
      stroke, computer-based, cognitive rehabilitation, and others. The methodological
      quality was evaluated. Statistical heterogeneity and standardized mean difference
      were used to compute the overall effect size and that of subgroups. Also
      publication bias of the selected studies was analysed. RESULTS: Twelve studies
      met the inclusion criteria including a total of 461 stroke survivors. Among
      studies, six RCT studies were rated as high methodological quality. Overall
      effect size was medium 0.54, and the 95% confidence interval was 0.33-0.74. The
      effect sizes of acute and chronic phase of stroke were both 0.54. They can be
      interpreted as medium effect size and were statistically significant. The
      statistical heterogeneity and publication bias were not significant. CONCLUSION:
      The present study provides evidence that CBCR is effective on improving cognitive
      function after stroke. We recommend conducting meta-analysis on subgroups of CBCR
      programs in further studies.

PMID- 23535801
TI  - Improvements in spasticity and motor function using a static stretching device
      for people with chronic hemiparesis following stroke.
AB  - We investigated the effect of a static stretching device on spasticity and motor
      function for people with chronic hemiparesis following stroke. Ten participants
      with chronic hemiparesis following stroke who had severe spasticity and
      incomplete weakness of the affected wrist and hand were recruited. The stretching
      device consisted of a resting hand splint, a finger and thumb stretching system,
      and a frame. The stretched state was maintained for 10 minutes/session, and the
      static stretching program was performed for 2 sessions/day and 7 days/week for 4
      weeks. Spasticity and motor function of the affected wrist and hand were assessed
      three times with intervals of 4 weeks (twice [Pre-1, Pre-2] before and once [Post
      1] after starting the static stretching program). The effect of the static
      stretching device was assessed using modified Ashworth scale (MAS) scores, by
      measuring active range of motion (AROM), and using the wrist and hand subsection
      of the Fugl-Meyer motor assessment (FMA). The main effects of the static
      stretching program on MAS scores for wrist and metacarpophalangeal (MCP) joints
      and FMA scores were significant. AROMs of MCPs and wrist showed an increase,
      however, no significant main effects of the static stretching program were
      observed. MAS in flexor muscles of MCP joints showed a significant decreased from
      Pre-2 (mean +/- standard deviation (SD): 2.56 +/- 0.55; median and interquartile
      range (IQR): 2.42, 2.12-3.08) to Post-1 (mean +/- SD: 1.05 +/- 0.49; median and
      IQR: 1.08, 0.87-1.50) (P < 0.001), and MAS in wrist flexor muscles also showed a
      significant decrease from Pre-2 (mean +/- SD: 3.20 +/- 0.78; median and IQR: 3.0,
      2.75-4.0) to Post-1 (mean +/- SD: 1.90 +/- 0.73; median and IQR: 2.0, 1.0-2.5) (P
      < 0.001). FMA score also showed a significant increase from Pre-2 (11.3 +/- 6.09)
      to Post-1 (14.5 +/- 6.20) (P < 0.001). It was found that the static stretching
      device effectively relieved spasticity and improved motor function in subjects
      with severe spasticity and incomplete weakness following stroke.

PMID- 23535802
TI  - The effect of an AFO-shaped elastic band on drop-foot gait in patients with
      central neurological lesions.
AB  - We investigated the effectiveness of an AFO-shaped band as an assistive walking
      device in patients with neurological lesions. The participants included 11
      patients with a recent history of a CVA and one multiple sclerosis patient. In
      each patient, the order of conditions (AFO, AFO-shaped band, barefoot) was
      randomized. Participants were required to walk on the GAITRite mat twice during
      each condition. The average gait velocity among patients using the AFO-shaped
      elastic band was significantly higher than those under barefoot conditions (p =
      0.015). Participants using the AFO-shaped elastic band also showed a
      significantly higher average number of steps per minute (cadence) as compared
      with the barefoot and AFO conditions (p = 0.007). Significant differences in
      stride length on the unaffected side were found between the AFO-shaped band and
      barefoot conditions (p = 0.029). Our results indicated that the AFO-shaped
      elastic band could be useful for patients with central neurological lesions with
      respect to gait, especially walking velocity, cadence, and stride length on the
      affected side. Thus, the AFO-shaped elastic band could be a practical tool for
      clinicians to train patients with central neurological lesions to walk.

PMID- 23535803
TI  - Changes of plantar pressure distributions following open and closed kinetic chain
      exercise in patients with stroke.
AB  - OBJECTIVE: The aim of this study is to investigate whether progressive resistive
      training with closed-kinetic chain (CKC) and open-kinetic chain (OKC) exercises
      could change plantar pressure distribution during walking in patients with
      stroke. METHODS: Thirty-nine stroke patients were recruited and randomly divided
      into a CKC exercise group (n = 13), an OKC exercise group (n = 13), and a control
      group (n = 13). Both CKC and OKC exercise groups performed their own respective
      training programs 5 times per week for 6 weeks, whereas no training was done in
      the control group. Barefoot plantar pressure distribution was measured during
      walking in terms of contact area (CA), peak contact force (PCF), and contact
      impulse (CI) on each of three foot regions (i.e. forefoot (FF), midfoot (MF), and
      hindfoot (HF)). RESULTS: In the CKC exercise group, there were significant
      changes in only the CA and PCF of HF. In the OKC exercise and control groups, no
      significant differences were found for all variables of plantar pressure
      distributions. CONCLUSION: We found that resistive training with closed kinetic
      chain exercises could be an effective treatment method for improving normal gait
      patterns in stroke patients. These findings may be attributed to the fact that
      CKC exercise induced use of the ankle and knee muscles and provided repetitive
      sensory input from the affected foot.

PMID- 23535804
TI  - The role of OLR1 polymorphisms in determining the risk and prognosis of ischemic
      stroke in a Chinese population.
AB  - AIM: To explore the role of rs11053646 polymorphism of oxidized low-density
      lipoprotein receptor 1 (OLR-1) gene in the susceptibility and prognosis of
      ischemic stoke (IS). METHODS: A total of 304 IS patients and 377 age and sex
      matched healthy controls were recruited. Patients were followed up for 6 months
      for recovery evaluation of stroke. Genotyping analyses of the rs11053646 G > C
      polymorphisms of OLR1 gene were performed. RESULTS: The genotype frequencies and
      alleles frequencies at rs11053646 were significantly differed between stroke
      subjects and control subjects (both P < 0.001). The presence of CC genotype was
      significantly higher in IS subjects than in controls (38% vs. 25%, P = 0.001).
      Similarly, the C allele carriage in IS was significantly higher than controls
      (59% vs. 49%, P < 0.001). Regression analysis showed the CC homozygote had a
      significantly increased risk for stroke (adjusted OR = 2.080; P = 0.001). The
      genotype of rs11053646 were not associated with the IS subtype and severity at
      admission, but determine the clinical outcome at 6 months after discharge from
      hospital. CONCLUSION: The rs11053646 polymorphism of OLR1 gene be used as a
      molecular marker for the susceptibility and prognosis of IS in Chinese
      population.

PMID- 23535805
TI  - Mild traumatic brain injury from primary blast vs. blunt forces: post-concussion
      consequences and functional neuroimaging.
AB  - INTRODUCTION: Primary blast forces may cause dysfunction from mild traumatic
      brain injury (mTBI). OBJECTIVE: To investigate the effects of primary blast
      forces, independent of associated blunt trauma and post-traumatic stress
      disorder, on sensitive post-concussive measures. METHODS: This study investigated
      post-concussive symptoms, functional health and well-being, cognition, and
      positron emission tomography (PET) neuroimaging among 12 Iraq or Afghanistan war
      veterans who sustained pure blast-force mTBI, compared to 12 who sustained pure
      blunt-force mTBI. RESULTS: Both groups had significantly lower scores than
      published norms on the Rivermead Post-Concussion Questionnaire (RPQ) and the SF36
      V Health Survey. Compared to the Blunt Group, the Blast Group had poorer scores
      on the Paced Auditory Serial Addition Test (PASAT) and greater PET hypometabolism
      in the right superior parietal region. Only the Blast Group had significant
      correlations of their RPQ, SF36-V Mental Composite Score, and PASAT scores with
      specific regional metabolic changes. CONCLUSION: This pilot study suggests that
      pure blast force mTBI may have greater post-concussive sequelae including
      deficits in attentional control and regional brain metabolism, compared to blunt
      mTBI. A disturbance of a right parietal-frontal attentional network is one
      potential explanation for these findings.

PMID- 23535806
TI  - A meta-analysis of functional outcome among older adults with traumatic brain
      injury.
AB  - OBJECTIVE: The objective of this study was to determine rates of functional
      outcomes, based on Glasgow Outcome Scale scores, among older adults (>60 years)
      after a traumatic brain injury. METHODS: An extensive database search was
      conducted. To be included all articles were published in English, included
      individuals 60 years or older, explicitly stated in-hospital GCS scores and GOS
      scores within one year post-TBI. Data was pooled on patient characteristics,
      mortality rates, time to death, and study design. RESULTS: A total of 11 studies
      were included in this review. Among individuals with severe TBI, favourable,
      unfavourable, and fatal outcomes were observed in 7.9% (CI 5.3%-11.8%), 13.8% (CI
      10.0%-18.8%) and 79.3% (CI 73.2%-84.4%), respectively. Among those with moderate
      TBI, favourable, unfavourable, and fatal outcomes were observed in 32.2% (CI
      18.0%-50.7%), 29.5% (CI 16.5%-47.0%), and 42.5% (CI 26.1%-60.7%), respectively.
      Among those with mild TBI, favourable, unfavourable, and fatal outcomes were
      observed in 80.5% (CI 53.2%-93.7%), 7.0% (CI 1.9%-22.7%), and 10.7% (CI 3.1%
      30.9%), respectively. CONCLUSION: This study has demonstrated the significant
      interaction between GCS and GOS among older adults. Although older adults may
      require aggressive and comprehensive treatment to achieve these favourable
      outcomes, high rates of unfavourable outcome should not justify the use of
      conservative treatment.

PMID- 23535807
TI  - Perception of muscular effort in multiple sclerosis.
AB  - BACKGROUND: Resistance exercise is effective in improving muscle strength and
      preventing muscle weakness in multiple sclerosis (MS) patients. Control of
      resistance training intensity based on perceived muscular effort is applicable to
      healthy individuals, yet there is no evidence of its utility for MS patients.
      OBJECTIVE: To compare perception of muscular effort in MS patients to healthy
      controls. METHODS: Based on their perception of muscular effort, twenty-five MS
      patients and twenty-eight controls adjusted static elbow extension tasks
      according to five levels on the OMNI-Resistance Exercise Scale. Elbow extension
      strength and muscle activity were measured via load cell dynamometer and surface
      electromyography (EMG) and related to each participant's maximal voluntary
      contraction (MVC) strength and muscle activity. Two-way analysis of variance was
      used to evaluate statistical significance. RESULTS: There were no statistically
      significant differences between MS patients and healthy controls, they produced
      similar relative torque values (F1 = 0.196; p > 0.05) and extensor muscle
      activities (F(2,617) = 1.556; p > 0.05) across all effort levels. CONCLUSION: No
      differences were found in the perception of muscular effort in MS patients and
      the age-matched control group. Future studies should explore, whether rating of
      perceived exertion is an effective instrument to control resistance training
      intensity in MS patients.

PMID- 23535808
TI  - One-year follow-up of the effects of community-based ambulation training for
      ambulatory patients with incomplete spinal cord injury: a case series.
AB  - PURPOSE: This study aimed to describe a community-based ambulation training for
      ambulatory patients with incomplete spinal cord injury (SCI) and then to report
      the results of the training. METHOD: Four patients with incomplete SCI
      participated in this study. The indoor and outdoor walking function was assessed
      at four intervals: pre-training, post-training, and at 4-week and 1-year follow
      ups after successful completion of the community-based ambulation training.
      Training consisted of the four-staged ambulation protocol with weekly-increased
      environmental demands, which consisted of 1-hour sessions six times a week for a
      4-week period (i.e., a total of 24 sessions). RESULTS: The walking function of
      all patients was remarkably improved after the training, and these effects were
      favorably maintained at the 4-week and 1-year follow-ups. CONCLUSION: These
      findings suggest that the use of community-based ambulation training is a
      beneficial therapeutic option to improve the walking function of ambulatory
      patients with incomplete SCI and to offer better opportunities for reintegration
      into community life.

PMID- 23535809
TI  - The effect of ice slushy ingestion and mouthwash on thermoregulation and
      endurance performance in the heat.
AB  - PURPOSE: The purpose of this study was to establish whether sensory factors
      associated with cold-beverage ingestion exert an ergogenic effect on endurance
      performance independent of thermoregulatory or cardiovascular factors. METHODS:
      Ten males performed three trials involving 90 min of steady state cycling (SS;
      62% VO2max) in the heat (32.1 +/- 0.9  degrees C, 40 +/- 2.4% relative humidity)
      followed by a 4 kJ/kg body mass time trial (TT). During SS, participants consumed
      an identical volume (260 +/- 38 g) of sports beverage (7.4% carbohydrate) every
      15 min as either ice slushy (-1  degrees C; ICE), thermoneutral liquid (37 
      degrees C; CON), or thermoneutral liquid consumption with expectorated ice slushy
      mouthwash (WASH). RESULTS: Rectal temperature, hydration status, heart rate, and
      skin blood flow were not different between trials. Gastrointestinal (pill)
      temperature was lower in ICE (35.6 +/- 2.7  degrees C) versus CON (37.4 +/- 0.7 
      degrees C, p = .05). Heat storage tended to be lower with ICE during SS (14.7 +/-
      8.4 W.m(-2), p = .08) and higher during TT (68.9 +/- 38.6 W.m(-2), p = .03)
      compared with CON (22.1 +/- 6.6 and 31.4 +/- 27.6 W.m(-2)). ICE tended to lower
      the rating of perceived exertion (RPE, 12.9 +/- 0.6, p = .05) and improve thermal
      comfort (TC, 4.5 +/- 0.2; p = .01) vs. CON (13.8 +/- 1.0 and 5.2 +/- 0.2
      respectively). WASH RPE (13.0 +/- 0.8) and TC (4.8 +/- 0.2) tended to be lower
      versus CON (p = .07 and p = .09 respectively). ICE improved performance (18:28 +/
      1:03) compared with CON (20:24 +/- 1:46) but not WASH (19:45 +/- 1:43).
      CONCLUSION: Improved performance with ICE ingestion likely resulted from the
      creation of a gastrointestinal heat sink, reducing SS heat storage. Although the
      benefits of cold-beverage consumption are more potent when there is ingestion,
      improved RPE, TC, and meaningful performance improvement with WASH supports an
      independent sensory effect of presenting a cold stimulus to the mouth.

PMID- 23535810
TI  - A platinum based organometallic turnstile.
AB  - The synthesis of an organometallic turnstile based on a Pt(II) centre as a hinge
      was achieved. Its dynamic behaviour in solution was investigated using 1D and 2D
      NMR techniques. Using Ag(I) cation as an effector, the switching between its open
      and closed states in solution was demonstrated.

PMID- 23535811
TI  - Pregabalin-induced akathisia.

PMID- 23535812
TI  - Recombinant activated factor VII use in critically ill patients: clinical
      outcomes and thromboembolic events.
AB  - BACKGROUND: Hemorrhage and coagulopathy are associated with morbidity and
      mortality in critically ill patients. Recombinant activated factor VII (rFVIIa)
      is frequently used in these situations to control bleeding; however, few
      controlled clinical trials have demonstrated clinical benefit and prolonged
      survival. OBJECTIVE: To compare clinical outcomes and thromboembolic events in
      intensive care unit (ICU) patients who received rFVIIa versus ICU patients who
      did not between 2000 and 2005. METHODS: A total of 2918 nonhemophiliac adult ICU
      patients, which included 1459 who received at least 1 dose of rFVIIa and 1459
      matched controls who did not, were included in a retrospective database study.
      Data were extracted from the Solucient ACTracker database, which included 550
      hospitals across the US. Measures included patient demographics, rFVIIa
      prescribing, death, thromboembolic events, discharge disposition, length of stay,
      and transfusion data. RESULTS: The most common primary diagnoses for patients
      receiving rFVIIa included traumatic brain injury, cirrhosis, and nontraumatic
      intracranial hemorrhage. Patients receiving rFVIIa were more likely to have
      comorbidities, including mechanical ventilation, acute kidney injury, sepsis,
      hemodialysis, and gastrointestinal bleeding (p < 0.0001). The average rFVIIa dose
      was 4.8 mg and 82% of patients received 1 dose. Compared to controls, patients
      receiving rFVIIa had greater odds of death (OR 2.1, 95% CI 1.8-2.6, p < 0.0001),
      transfusion (OR 2.1, 95% CI 1.8-2.5, p < 0.0001), and longer length of stay (p <
      0.001). There was no significant difference in thromboembolic events between
      groups. CONCLUSIONS: While we cannot show direct causality between rFVIIa and the
      poor clinical outcomes documented in ICU patients, they provide important insight
      for critical care clinicians.

PMID- 23535813
TI  - Behind closed doors: medication storage and disposal in the home.
AB  - BACKGROUND: More than half of all medications are inappropriately prescribed,
      dispensed, or sold and only 50% of patients take their medications correctly.
      Oftentimes, unwanted or expired medications are saved for later use, stored
      indefinitely, or disposed via the sink, toilet, or garbage. OBJECTIVE: To
      determine how residents in Cook County, Illinois, use, store, and dispose of
      their medications to assess the possible impact of these medications on health
      care and the environment. METHODS: Researchers at the University of Illinois
      conducted a survey of Cook County residents over a 13-week period. Residents were
      surveyed regarding their use, storage, and disposal of prescription and
      nonprescription medications. RESULTS: From 3954 telephone numbers generated
      through random-digit dialing, 445 telephone interviews were completed. Eighty-one
      and a half percent of respondents had prescription medications and 92.4% had
      nonprescription medications in their homes. On average, respondents possessed 4.4
      distinct prescription and 5.5 distinct nonprescription medications. Despite
      possessing a number of medications, approximately 30% of respondents stated that
      they took no medication on a regular basis; 59% of respondents reported disposing
      medications in the household gar bage and 31% flushed them down the toilet or
      sink. Over 80% of respondents stated that they had never received information
      about proper medication disposal. Thirty-seven percent reported having leftover
      unexpired medications from a previous illness. Of these, 63% stopped taking their
      medications because they believed that they no longer needed them or because they
      felt better. Thirty-two percent of respondents expected to have leftover
      prescription medications within the next 6 months. CONCLUSIONS: Almost all
      respondents had excess and leftover medications in their homes. This may be a
      result of both overprescribing and poor medication adherence. In addition to the
      potential human health risk of nonadherence, disposal of excess medication raises
      concerns about their environmental impact and safety.

PMID- 23535814
TI  - Ischemic colitis with type I interferons used in the treatment of hepatitis C and
      multiple sclerosis: an evaluation from the food and drug administration adverse
      event reporting system and review of the literature.
AB  - OBJECTIVE: To better characterize the association between type I interferons and
      ischemic colitis (IC) in patients with the hepatitis C virus (HCV) and multiple
      sclerosis (MS), by analyzing reports submitted to the Food and Drug
      Administration (FDA) Adverse Event Reporting System (AERS) and the published
      literature. DATA SOURCES: A total of 2,562,390 reports of adverse events between
      January 2003 and June 2011 were downloaded from the FDA AERS. A literature review
      was performed on PubMed (January 1966-August 2012) using the MeSH terms
      interferon or interferon alfa or interferon beta and ischemic colitis separated
      by the Boolean operator "and" between the first 3 terms and the last term.
      Additional literature was identified by conducting a hand search of the reference
      list of the published literature identified in the initial search. STUDY
      SELECTION AND DATA EXTRACTION: Cases were restricted to those with an indication
      of HCV or MS, a primary suspect drug of a type I interferon, and a reaction of
      IC. Full-length reports were requested and organized by type of interferon, age,
      sex, concomitant drugs, and comorbidities. The Naranjo probability scale was used
      to define cases as definite, probable, possible, or doubtful drug-induced adverse
      events. DATA SYNTHESIS: Type I interferons, including interferon alfa (IFN-alpha)
      and interferon beta (IFN-beta), are approved for the treatment of HCV and MS. IFN
      alpha has been shown to induce IC, but a relationship between type I interferons
      and IC has not been clarified in the medical literature. Fifty-six primary
      suspect reports of type I interferons associated with IC in patients with HCV or
      MS were identified from the FDA AERS. Seventeen cases were reported with IFN
      alpha and 39 cases were reported with IFN-beta. The majority of the cases were in
      females (80%) and those between the ages of 50 and 65 years (52%). The Naranjo
      probability scale identified 13 probable and 4 possible cases of IFN-alpha
      induced IC, and 19 probable and 20 possible cases of IFN-beta-induced IC. In the
      literature, 11 cases of IFN-alpha-induced IC were reported, while there were no
      reports with IFN-beta. CONCLUSIONS: Our study suggests a possible association
      between treatment with type I interferons and the development of IC. Further
      research to determine the mechanism of this association is warranted.

PMID- 23535815
TI  - Acute pulmonary emboli in a patient on long-term dabigatran therapy.
AB  - OBJECTIVE: To describe the case of a patient who developed acute pulmonary emboli
      (PE) despite long-term anticoagulation with dabigatran. CASE SUMMARY: A 69-year
      old obese woman was hospitalized for worsening shortness of breath, dyspnea on
      exertion, and left pleuritic chest pain. On admission, a computed tomography
      angiogram revealed acute bilateral PE, despite use of dabigatran for atrial
      fibrillation for approximately 5 years prior to admission. Dabigatran was stopped
      and therapeutic enoxaparin was initiated concomitantly with warfarin. An
      investigation into possible causes for the development of the PE, including
      hypercoagulability, was unrevealing. Since dabigatran should have protected
      against PE, the patient was questioned regarding adherence to her regimen. She
      stated that she was adherent but reported using a pillbox. The patient was
      discharged home on warfarin with an enoxaparin bridge until her international
      normalized ratio was at least 2.0. DISCUSSION: The underlying cause for the
      patient's acute PE is unknown but could possibly be attributed to obesity and
      reduced mobility. Although dabigatran should have prevented PE, the presence of
      interacting drugs, patient-specific pharmacokinetics, suboptimal medication
      storage, and laboratory abnormalities may have resulted in reduced dabigatran
      exposure and protection. This is a reasonable hypothesis; however, the patient
      did not develop a stroke while receiving dabigatran. CONCLUSIONS: Our patient
      developed acute bilateral PE despite receiving long-term anticoagulation with
      dabigatran. While it is possible that patient-specific factors resulted in
      reduced dabigatran exposure and efficacy, conclusions cannot be made.

PMID- 23535816
TI  - Impact of a protocol advocating dexmedetomidine over propofol sedation after
      robotic-assisted direct coronary artery bypass surgery on duration of mechanical
      ventilation and patient safety.
AB  - BACKGROUND: Controversy remains whether propofol or dexmedetomidine is the
      preferred sedative following cardiac surgery. Dexmedetomidine may offer
      advantages over propofol among patients undergoing robotic-assisted, minimally
      invasive, direct coronary artery bypass (MIDCAB) surgery given the rapidity with
      which this population is usually extubated after surgery. OBJECTIVE: To measure
      the impact of a surgery protocol advocating use of dexmedetomidine rather than
      propofol after MIDCAB surgery on discontinuation of mechanical ventilation and
      patient safety. METHODS: The records on consecutive adults undergoing MIDCAB
      surgery who received postoperative sedation with propofol or dexmedetomidine at a
      508-bed academic medical center were analyzed before and after implementation of
      a post-MIDCAB surgery protocol advocating dexmedetomidine use. RESULTS: Seventy
      three propofol patients were compared with 53 dexmedetomidine patients. The
      groups were similar, except propofol patients were older (p = 0.002) and more
      likely to have underlying heart failure that was either moderate or severe (New
      York Heart Association class III or IV) (p = 0.0001). Time (median [interquartile
      range]) to extubation (hours) was shorter in the dexmedetomidine group (5.0 [3.6
      7.0] vs 9.8 [5.0-16.3]; p = 0.0001). A Cox proportional hazards model revealed
      that patient age (p = 0.001) and duration of surgery (p = 0.003) influenced time
      to extubation between the dexmedetomidine and propofol groups but the presence of
      moderate or severe heart failure (p = 0.438), the number of coronary vessels
      operated on (p = 0.130), use of an opioid (p = 0.791), or the total dose of
      morphine administered (p = 0.215) did not. During sedation administration, more
      propofol-treated patients experienced 1 or more episodes of hypotension (systolic
      blood pressure <=80 mm Hg, 11.6% vs 0%; p = 0.02), tachycardia (heart rate >=120
      beats/min, 8.6% vs 0%; p = 0.04), and unarousability (Sedation Agitation Scale
      score <=2, 30.0% vs 9.4%; p = 0.03). CONCLUSIONS: Use of a protocol promoting
      dexmedetomidine, rather than propofol sedation, after MIDCAB surgery facilitates
      faster discontinuation of mechanical ventilation and is associated with greater
      hemodynamic stability and arousability.

PMID- 23535817
TI  - The rebirth of progesterone in the prevention of preterm labor.
AB  - OBJECTIVE: To evaluate data since 2003 on the efficacy and safety of progesterone
      supplementation in the prevention of preterm labor. DATA SOURCES: A MEDLINE and
      Ovid database search (January 2003-September 2012) was performed using the search
      terms preterm, progesterone, and 17alpha-hydroxyprogesterone caproate. All
      relevant abstracts were reviewed. STUDY SELECTION: For efficacy and safety data,
      the search was limited to randomized, double-blind, placebo-controlled trials
      with the primary outcome of preterm delivery, fetal loss, or neonatal morbidity
      or mortality. Quality of the studies was assessed using the CONSORT (Consolidated
      Standards of Reporting Trials) guidelines for reporting parallel-group randomized
      trials. Eleven articles were selected for review. DATA SYNTHESIS: Preterm birth,
      prior to 37 weeks' gestation, remains the leading cause of neonatal morbidity and
      mortality in the US due to lack of treatment options. Recently, the use of
      progesterone to prevent preterm labor, deemed decades ago to be ineffective, has
      been reexamined. Progesterone formulations and dosage regimens varied greatly
      between studies. In patients with prior preterm birth or shortened cervix shown
      on transvaginal ultrasound, progesterone appears efficacious in reducing the rate
      of preterm birth. However, this benefit was not demonstrated in multiple
      gestation pregnancies. Overall, progesterone was well tolerated and appeared safe
      for mother and fetus. More studies are needed to confirm the dosage regimen and
      population that will benefit most from progesterone. CONCLUSIONS: Progesterone
      appears to be safe and efficacious in reducing the risk of preterm birth in a
      select group of high-risk women with prior spontaneous preterm births and those
      with an ultrasound-confirmed short cervix. Women with multiple gestations do not
      benefit from progesterone supplementation.

PMID- 23535818
TI  - Congenital tibial dysplasia with lateral bowing and duplication of hallux: case
      presentations.
AB  - This article reports on two children with congenital unilateral tibial dysplasia
      with lateral bowing with no associated sagittal plane deformity. In both cases,
      it is associated with ipsilateral duplication of the hallux. Long-term follow-up
      of the patients showed spontaneous, almost complete resolution of the bowing
      without progressing into fracture or pseudoarthrosis. Leg length discrepancy
      appeared to be the only orthopedic sequela related to this phenomenon.

PMID- 23535819
TI  - Lack of association of the autophagy-related gene polymorphism ATG16L1 rs2241880
      in RA predisposition.

PMID- 23535820
TI  - Peripheral arterial disease in patients with Behcet's disease.

PMID- 23535821
TI  - Global increases in both common and rare copy number load associated with autism.
AB  - Children with autism have an elevated frequency of large, rare copy number
      variants (CNVs). However, the global load of deletions or duplications, per se,
      and their size, location and relationship to clinical manifestations of autism
      have not been documented. We examined CNV data from 516 individuals with autism
      or typical development from the population-based Childhood Autism Risks from
      Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by
      segmental duplications (genomic hotspots) for events >50 kbp and the entire
      genomic backbone for variants >300 kbp using a custom targeted DNA microarray.
      This analysis was complemented by a separate study of five highly dynamic
      hotspots associated with autism or developmental delay syndromes, using a finely
      tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity.
      In both studies, a significant increase in the number of base pairs of
      duplication, but not deletion, was associated with autism. Significantly elevated
      levels of CNV load remained after the removal of rare and likely pathogenic
      events. Further, the entire CNV load detected with the finely tiled array was
      contributed by common variants. The impact of this variation was assessed by
      examining the correlation of clinical outcomes with CNV load. The level of
      personal and social skills, measured by Vineland Adaptive Behavior Scales,
      negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV
      load for the affected children; the strongest association was found for
      communication (P = 0.048) and socialization (P = 0.022) scores. We propose that
      CNV load, predominantly increased genomic base pairs of duplication, predisposes
      to autism. 

PMID- 23535822
TI  - Defective skeletal muscle growth in lamin A/C-deficient mice is rescued by loss
      of Lap2alpha.
AB  - Mutations in lamin A/C result in a range of tissue-specific disorders
      collectively called laminopathies. Of these, Emery-Dreifuss and Limb-Girdle
      muscular dystrophy 1B mainly affect striated muscle. A useful model for
      understanding both laminopathies and lamin A/C function is the Lmna(-/-) mouse.
      We found that skeletal muscle growth and muscle satellite (stem) cell
      proliferation were both reduced in Lmna(-/-) mice. Lamins A and C associate with
      lamina-associated polypeptide 2 alpha (Lap2alpha) and the retinoblastoma gene
      product, pRb, to regulate cell cycle exit. We found Lap2alpha to be upregulated
      in Lmna(-/-) myoblasts (MBs). To specifically test the contribution of elevated
      Lap2alpha to the phenotype of Lmna(-/-) mice, we generated Lmna(-/-)Lap2alpha(-/
      ) mice. Lifespan and body mass were increased in Lmna(-/-)Lap2alpha(-/-) mice
      compared with Lmna(-/-). Importantly, the satellite cell proliferation defect was
      rescued, resulting in improved myogenesis. Lmna(-/-) MBs also exhibited increased
      levels of Smad2/3, which were abnormally distributed in the cell and failed to
      respond to TGFbeta1 stimulation as in control cells. However, using SIS3 to
      inhibit signaling via Smad3 reduced cell death and augmented MB fusion. Together,
      our results show that perturbed Lap2alpha/pRb and Smad2/3 signaling are important
      regulatory pathways mediating defective muscle growth in Lmna(-/-) mice, and that
      inhibition of either pathway alone or in combination can ameliorate this
      deleterious phenotype. 

PMID- 23535823
TI  - A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently
      associated with abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated
      heritability (0.7); however, only a small number of associated genetic loci have
      been reported to date. In contrast, over 100 loci have now been reproducibly
      associated with either blood lipid profile and/or coronary artery disease (CAD)
      (both risk factors for AAA) in large-scale meta-analyses. This study employed a
      staged design to investigate whether the loci for these two phenotypes are also
      associated with AAA. Validated CAD and dyslipidaemia loci underwent screening
      using the Otago AAA genome-wide association data set. Putative associations
      underwent staged secondary validation in 10 additional cohorts. A novel
      association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839
      G allele, which has been previously associated with both dyslipidaemia and CAD,
      reached genome-wide significance in 11 combined independent cohorts (meta
      analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76
      0.85, P = 7.2 * 10(-14)). Modelling for confounding interactions of concurrent
      dyslipidaemia, heart disease and other risk factors suggested that this marker is
      an independent predictor of AAA susceptibility. In conclusion, a genetic marker
      associated with cardiovascular risk factors, and in particular concurrent
      vascular disease, appeared to independently contribute to susceptibility for AAA.
      Given the potential genetic overlap between risk factor and disease phenotypes,
      the use of well-characterized case-control cohorts allowing for modelling of
      cardiovascular disease risk confounders will be an important component in the
      future discovery of genetic markers for conditions such as AAA. 

PMID- 23535824
TI  - Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which
      associates with TERT expression.
AB  - Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple
      cancer types have been reported. We have previously shown evidence for a strong
      association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic
      in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To
      comprehensively evaluate the association between genetic variation across this
      region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs
      using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by
      imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL
      consortium. Multiple stepwise logistic regression analysis identified four
      signals in the promoter or intronic regions of TERT that independently associated
      with PrCa risk. Gene expression analysis of normal prostate tissue showed
      evidence that SNPs within one of these regions also associated with TERT
      expression, providing a potential mechanism for predisposition to disease.

PMID- 23535825
TI  - Common genetic determinants of breast-cancer risk in East Asian women: a
      collaborative study of 23 637 breast cancer cases and 25 579 controls.
AB  - In a consortium including 23 637 breast cancer patients and 25 579 controls of
      East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in
      67 independent breast cancer susceptibility loci recently identified by genome
      wide association studies (GWASs) conducted primarily in European-ancestry
      populations. SNPs in 31 loci showed an association with breast cancer risk at P <
      0.05 in a direction consistent with that reported previously. Twenty-one of them
      remained statistically significant after adjusting for multiple comparisons with
      the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs
      showed a significantly different association with breast cancer risk by estrogen
      receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the
      seven other SNPs showed a stronger association with ER-positive than ER-negative
      cancer. This study replicated all five genetic risk variants initially identified
      in Asians and provided evidence for associations of breast cancer risk in the
      East Asian population with nearly half of the genetic risk variants initially
      reported in GWASs conducted in European descendants. Taken together, these common
      genetic risk variants explain ~10% of excess familial risk of breast cancer in
      Asian populations.

PMID- 23535828
TI  - Recent developments in design and synthesis of bicyclic azasugars, carbasugars
      and related molecules as glycosidase inhibitors.
AB  - The importance of glycosidase inhibitors and especially the bicyclic molecules
      has led to design and assessment of many analogs of naturally occurring
      molecules. This review focuses on the synthesis and enzyme inhibitions of a few
      selected (synthetic or non-naturally occurring) molecules that have been reported
      in the last decade, which allow one to draw some connection between varying the
      structural features and their effect on glycosidase inhibitions. It is expected
      that further improvements based on these features could lead to improved
      inhibitors.

PMID- 23535827
TI  - Force nanoscopy of cell mechanics and cell adhesion.
AB  - Cells are constantly exposed to mechanical stimuli in their environment and have
      several evolved mechanisms to sense and respond to these cues. It is becoming
      increasingly recognized that many cell types, from bacteria to mammalian cells,
      possess a diverse set of proteins to translate mechanical cues into biochemical
      signalling and to mediate cell surface interactions such as cell adhesion.
      Moreover, the mechanical properties of cells are involved in regulating cell
      function as well as serving as indicators of disease states. Importantly, the
      recent development of biophysical tools and nanoscale methods has facilitated a
      deeper understanding of the role that physical forces play in modulating cell
      mechanics and cell adhesion. Here, we discuss how atomic force microscopy (AFM)
      has recently been used to investigate cell mechanics and cell adhesion at the
      single-cell and single-molecule levels. This knowledge is critical to our
      understanding of the molecular mechanisms that govern mechanosensing,
      mechanotransduction, and mechanoresponse in living cells. While pushing living
      cells with the AFM tip provides a means to quantify their mechanical properties
      and examine their response to nanoscale forces, pulling single surface proteins
      with a functionalized tip allows one to understand their role in sensing and
      adhesion. The combination of these nanoscale techniques with modern molecular
      biology approaches, genetic engineering and optical microscopies provides a
      powerful platform for understanding the sophisticated functions of the cell
      surface machinery, and its role in the onset and progression of complex diseases.

PMID- 23535826
TI  - Helicobacter Pylori "Test-and-Treat" Strategy for Management of Dyspepsia: A
      Comprehensive Review.
AB  - OBJECTIVES: Deciding on whether the Helicobacter pylori test-and-treat strategy
      is an appropriate diagnostic-therapeutic approach for patients with dyspepsia
      invites a series of questions. The aim present article addresses the test-and
      treat strategy and attempts to provide practical conclusions for the clinician
      who diagnoses and treats patients with dyspepsia. METHODS: Bibliographical
      searches were performed in MEDLINE using the keywords Helicobacter pylori, test
      and-treat, and dyspepsia. We focused mainly on data from randomized controlled
      trials (RCTs), systematic reviews, meta-analyses, cost-effectiveness analyses,
      and decision analyses. RESULTS: Several prospective studies and decision analyses
      support the use of the test-and-treat strategy, although we must be cautious when
      extrapolating the results from one geographical area to another. Many factors
      determine whether this strategy is appropriate in each particular area. The test
      and-treat strategy will cure most cases of underlying peptic ulcer disease,
      prevent most potential cases of gastroduodenal disease, and yield symptomatic
      benefit in a minority of patients with functional dyspepsia. Future studies
      should be able to stratify dyspeptic patients according to their likelihood of
      improving after treatment of infection by H. pylori. CONCLUSIONS: The test-and
      treat strategy will cure most cases of underlying peptic ulcer disease and
      prevent most potential cases of gastroduodenal disease. In addition, a minority
      of infected patients with functional dyspepsia will gain symptomatic benefit.
      Several prospective studies and decision analyses support the use of the test-and
      treat strategy. The test-and-treat strategy is being reinforced by the
      accumulating data that support the increasingly accepted idea that "the only good
      H. pylori is a dead H. pylori".

PMID- 23535830
TI  - Giant pseudoaneurysm of the ascending aorta after valve replacement. Medical
      follow-up for 22 months without complication.

PMID- 23535829
TI  - Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by
      alpha5GABAA receptor-preferring inverse agonists.
AB  - BACKGROUND: Animal studies have shown that memory deficits in the early post
      anaesthetic period can be prevented by pre-treatment with an inverse agonist that
      preferentially inhibits alpha5 subunit-containing gamma-aminobutyric acid type A
      (alpha5GABA(A)) receptors. The goal of this in vitro study was to determine
      whether inverse agonists that inhibit alpha5GABA(A) receptors reduce anaesthetic
      potentiation of GABAA receptor activity. METHODS: Cultures of hippocampal
      neurones were prepared from Swiss white mice, wild-type mice (genetic background
      C57BL/6J and Sv129Ev) and alpha5GABA(A)receptor null mutant (Gabra5-/-) mice.
      Whole-cell voltage clamp techniques were used to study the effects of the
      alpha5GABA(A) receptor-preferring inverse agonists L-655,708 and MRK-016 on
      anaesthetic potentiation of GABA-evoked currents. RESULTS: L-655,708 (50 nM)
      reduced sevoflurane potentiation of GABA-evoked current in wild-type neurones but
      not Gabra5-/- neurones, and produced a rightward shift in the sevoflurane
      concentration-response plot [sevoflurane EC50: 1.9 (0.1) mM; sevoflurane+L
      655,708 EC(50): 2.4 (0.2) mM, P<0.05]. Similarly, L-655,708 (50 nM) reduced
      isoflurane potentiation of GABA-evoked current [isoflurane: 4.0 (0.6) pA pF(-1);
      isoflurane+L-655,708: 3.1 (0.5) pA pF(-1), P<0.01]. MRK-016 also reduced
      sevoflurane and isoflurane enhancement of GABA-evoked current [sevoflurane: 1.5
      (0.1) pA pF(-1); sevoflurane+MRK-016 (10 nM): 1.2 (0.1) pA pF(-1), P<0.05;
      isoflurane: 3.5 (0.3) pA pF(-1); isoflurane+MRK-016 (1 nM): 2.9 (0.2) pA pF(-1),
      P<0.05]. CONCLUSIONS: L-655,708 and MRK-016 reduced the potentiation by inhaled
      anaesthetics of GABAA receptor activated by a low concentration of GABA. Future
      studies are required to determine whether this effect contributes to the memory
      preserving properties of inverse agonists after anaesthesia.

PMID- 23535831
TI  - Osteoprotegerin as a marker of cardiovascular risk in patients on peritoneal
      dialysis.
AB  - INTRODUCTION: Arterial thickening contributes to elevated cardiovascular risk in
      patients on maintenance renal replacement therapy. The common carotid artery
      intima-media thickness (CCA-IMT) is an early atherosclerotic marker and may be
      used to assess the stratification of atherosclerotic advancement and resultant
      arterial calcification. OBJECTIVES: The aim of the study was to evaluate the
      associations between atherosclerotic changes in the common carotid arteries
      expressed as the CCA-IMT and the body mass index (BMI), serum lipid levels, C
      reactive protein (CRP), and selected bone metabolism parameters including
      phosphorus, calcium, intact parathormone (iPTH), alkaline phosphatase,
      osteopontin, osteoprotegerin, osteocalcin, fetuin A, and fibroblast growth factor
      23 (FGF-23) in patients treated with peritoneal dialysis. PATIENTS AND METHODS:
      The study included 67 patients with chronic kidney disease (36 men and 31 women)
      aged 53 +/-13 years (range, 19-75 years) treated with peritoneal dialysis for 30
      +/-24 months. The CCA-IMT was assessed by ultrasonography using Acuson 128/10 XP.
      The BMI was calculated using the Quetelet formula. Serum lipid levels,
      phosphorus, calcium, iPTH, alkaline phosphatase, and CRP were measured using
      standard laboratory methods, while fetuin A, osteocalcin, osteoprotegerin,
      osteopontin, and FGF-23 using commercial enzyme-linked immunosorbent assay kits.
      RESULTS: Positive correlations were observed between CCA-IMT and age (r = 0.54, P
      <0.0001), BMI (r = 0.39, P = 0.003), and osteoprotegerin (r = 0.38, P = 0.004).
      In a multiple regression analysis, age (r = 0.41, P = 0.01), osteocalcin (r =
      0.34, P = 0.04), and log-transformed osteoprotegerin values (r = 0.38, P = 0.02)
      remained independently associated with the CCA-IMT. The highest CCA-IMT values
      (0.85 +/-0.21) were observed in patients with osteoprotegerin concentrations in
      the upper tertile. Osteoprotegerin concentrations strongly and positively
      correlated with the duration of dialysis treatment (r = 0.55, P <0.0001).
      CONCLUSIONS: The CCA-IMT has been shown to be a reliable noninvasive measure of
      subclinical atherosclerosis and, therefore, of associated increased vascular
      risk. Elevated serum osteoprotegerin levels may be useful as a prognostic marker
      of cardiovascular risk in dialyzed patients.

PMID- 23535832
TI  - Diversity-oriented synthesis of pyrazolo[4,3-b]indoles by gold-catalysed three
      component annulation: application to the development of a new class of CK2
      inhibitors.
AB  - Pyrazolo[4,3-b]indole derivatives have been designed as novel CK2 inhibitor
      compounds based on the binding mode analysis of a previously reported
      phenylpyrazole-type CK2 inhibitor. A series of pyrazolo[4,3-b]indoles and related
      dihydropyrazolo[4,3-b]indoles were efficiently prepared from simple starting
      materials using a gold-catalysed three-component annulation reaction as a key
      step. Several of the newly synthesized compounds displayed high levels of
      inhibitory activity, indicating that the pyrazolo[4,3-b]indole core represents a
      promising scaffold for the development of potent CK2 inhibitors.

PMID- 23535833
TI  - Break in volition: a virtual reality study in patients with obsessive-compulsive
      disorder.
AB  - Research in obsessive-compulsive disorder (OCD) produced inconsistent results in
      demonstrating an association between patients' symptom severity and their
      cognitive impairments. The process involved in volition aspects of behavioral
      syndromes can be extensively analyzed using specific tests developed in virtual
      environments, more suitable to manipulate rules and possible breaks of the normal
      task execution with different, confusing or stopping instructions. The study
      involved thirty participants (15 OCD patients and 15 controls) during task
      execution and the relative interferences. At this purpose, the virtual version of
      Multiple Errands Test was used. Virtual reality setting, with a higher ecological
      validity respect to a classic neuropsychological battery, allowed us to take into
      account deficits of volition and the relative dysexecutive functions associated
      with OCD patients. The proposed paradigm also allows the development of
      innovative prototypes of coevolving technologies based on new theories and models
      and deeper understanding of human behavior. 

PMID- 23535834
TI  - The enhanced oral response to the 5-HT2 agonist Ro 60-0175 in parkinsonian rats
      involves the entopeduncular nucleus: electrophysiological correlates.
AB  - Lesions of nigrostriatal dopaminergic neurons as seen in Parkinson's disease (PD)
      increase orofacial responses to serotonergic (5-HT) agonists in rodents. Although
      this response to 5-HT agonists has been related to aberrant signalling in the
      basal ganglia, a group a subcortical structures involved in the control of motor
      behaviours, it deserves additional studies with respect to the specific loci
      involved. Using measurements of orofacial activity, as well as single-cell
      recordings in vivo, we have studied the role of the entopeduncular nucleus (EPN;
      equivalent to the internal globus pallidus of primates), an output structure of
      basal ganglia, in the hypersensitized responses to a 5-HT agonist in sham- or
      unilaterally dopamine-depleted rats. Intra-EPN injections of Ro 60-0175 (0.3 and
      1 MUg/100 nl) promoted robust oral movements in 6-OHDA rats without affecting
      oral activity in sham-depleted rats. Peripheral administration of Ro 60-0175 (3
      mg/kg ip) decreased EPN neuronal firing rate in 6-OHDA rats compared to sham
      depleted rats. Such an effect was also observed when the agonist (0.2 MUg/20 nl)
      was locally applied onto EPN neurons. These data demonstrate the contribution of
      EPN to hypersensitized responses to 5-HT agonists in a rat model of PD. 

PMID- 23535836
TI  - Inter-limb transfer of ballistic motor skill following non-dominant limb training
      in young and older adults.
AB  - We recently reported considerably less inter-limb transfer in older, compared to
      young, adults following dominant (right) hand motor training (Hinder et al. in J
      Appl Physiol 110:166-175, 2011). This occurred despite the fact that both age
      groups exhibited similar performance improvements in the trained limb. However,
      asymmetries can exist with respect to the degree of transfer observed in some
      tasks, depending upon which limb undertakes the training. Accordingly, here we
      investigated inter-limb transfer following left hand ballistic motor training in
      young (n = 15; mean age 21.2 years) and older (n = 15; mean age 70.3 years) right
      handers. Following motor training that required participants to maximally abduct
      the left index finger, both groups exhibited significant performance improvements
      in the trained left hand. Moreover, the extent of inter-limb transfer was
      substantial and indistinguishable between the two age groups. Transcranial
      magnetic stimulation revealed that both age groups exhibited bilateral increases
      in cortical excitability following unilateral training, indicating that
      unilateral training affects both the trained and untrained hemisphere. However,
      only for young adults was the extent of the performance gain in the trained hand
      able to predict the degree of transfer. These findings suggest that different
      mechanisms may mediate inter-limb transfer of ballistic motor tasks for older and
      young adults. Because such tasks evoke similar neural responses to those observed
      following strength training (Selvanayagam et al. in J Appl Physiol 111:367-375,
      2011; Carroll et al. in Acta Physiol 202:119-140, 2011), our findings have
      important implications for rehabilitation paradigms following stroke or limb
      immobilisation due to injury.

PMID- 23535835
TI  - Barking up the wrong free: readiness potentials reflect processes independent of
      conscious will.
AB  - In the early 1980s, Libet found that a readiness potential (RP) over central
      scalp locations begins on average several hundred milliseconds before the
      reported time of awareness of willing to move (W). Haggard and Eimer Exp Brain
      Res 126(1):128-133, (1999) later found no correlation between the timing of the
      RP and W, suggesting that the RP does not reflect processes causal of W. However,
      they did find a positive correlation between the onset of the lateralized
      readiness potential (LRP) and W, suggesting that the LRP might reflect processes
      causal of W. Here, we report a failure to replicate Haggard and Eimer's LRP
      finding with a larger group of participants and several variations of their
      analytical method. Although we did find a between-subject correlation in just one
      of 12 related analyses of the LRP, we crucially found no within-subject
      covariation between LRP onset and W. These results suggest that the RP and LRP
      reflect processes independent of will and consciousness. This conclusion has
      significant implications for our understanding of the neural basis of motor
      action and potentially for arguments about free will and the causal role of
      consciousness. 

PMID- 23535837
TI  - Visually guided adjustments of body posture in the roll plane.
AB  - Body position relative to gravity is continuously updated to prevent falls.
      Therefore, the brain integrates input from the otoliths, truncal graviceptors,
      proprioception and vision. Without visual cues estimated direction of gravity
      mainly depends on otolith input and becomes more variable with increasing roll
      tilt. Contrary, the discrimination threshold for object orientation shows little
      modulation with varying roll orientation of the visual stimulus. Providing earth
      stationary visual cues, this retinal input may be sufficient to perform self
      adjustment tasks successfully, with resulting variability being independent of
      whole-body roll orientation. We compared conditions with informative (earth
      fixed) and non-informative (body-fixed) visual cues. If the brain uses
      exclusively retinal input (if earth-stationary) to solve the task, trial-to-trial
      variability will be independent from the subject's roll orientation.
      Alternatively, central integration of both retinal (earth-fixed) and extra
      retinal inputs will lead to increasing variability when roll-tilted. Subjects,
      seated on a motorized chair, were instructed to (1) align themselves parallel to
      an earth-fixed line oriented earth-vertical or roll-tilted 75 degrees  clockwise;
      (2) move a body-fixed line (aligned with the body-longitudinal axis or roll
      tilted 75 degrees  counter-clockwise to it) by adjusting their body position
      until the line was perceived earth-vertical. At 75 degrees  right-ear-down
      position, variability increased significantly (p < 0.05) compared to upright in
      both paradigms, suggesting that, despite the earth-stationary retinal cues, extra
      retinal input is integrated. Self-adjustments in the roll-tilted position were
      significantly (p < 0.01) more precise for earth-fixed cues than for body-fixed
      cues, underlining the importance of earth-stable visual cues when estimates of
      gravity become more variable with increasing whole-body roll.

PMID- 23535838
TI  - Long-term strain improvements accumulate mutations in regulatory elements
      responsible for hyper-production of cellulolytic enzymes.
AB  - Long-term strain improvements through repeated mutagenesis and screening have
      generated a hyper-producer of cellulases and hemicellulases from Penicillium
      decumbens 114 which was isolated 30 years ago. Here, the genome of the hyper
      producer P. decumbens JU-A10-T was sequenced and compared with that of the wild
      type strain 114-2. Further, the transcriptomes and secretomes were compared
      between the strains. Selective hyper-production of cellulases and hemicellulases
      but not all the secreted proteins was observed in the mutant, making it a more
      specific producer of lignocellulolytic enzymes. Functional analysis identified
      that changes in several transcriptional regulatory elements played crucial roles
      in the cellulase hyper-producing characteristics of the mutant. Additionally, the
      mutant showed enhanced supply of amino acids and decreased synthesis of secondary
      metabolites compared with the wild-type. The results clearly point out that we
      can target gene regulators and promoters with minimal alterations of the genetic
      content but maximal effects in genetic engineering.

PMID- 23535839
TI  - Phosphorylation of AKT pathway proteins is not predictive of benefit of taxane
      therapy in early breast cancer.
AB  - Results from the NSABP B-28 trial suggest AKT activation may predict reduced
      benefit from taxanes following standard anthracycline therapy. Pre-clinical data
      support a link between PI3 K/AKT signalling and taxane resistance. Using the UK
      taxotere as adjuvant chemotherapy trial (TACT), we tested the hypothesis that
      activation of AKT or downstream markers, p70S6K or p90RSK, identifies patients
      with reduced benefit from taxane chemotherapy. TACT is a multi-centre open-label
      phase III trial comparing four cycles of standard FEC (fluorouracil, epirubicin,
      cyclophosphamide) followed by four cycles of docetaxel versus eight cycles of
      anthracycline-based chemotherapy. Samples from 3,596 patients were available for
      the current study. We performed immunohistochemical analysis of activation of
      AKT, p70S6 K and p90RSK. Using a training set with multiple cut-offs for
      predictive values (10 % increments in expression), we found no evidence for a
      treatment by marker interaction for pAKT473, pS6 or p90RSK. pAKT473, pS6 and
      p90RSK expression levels were weakly correlated. A robust, preplanned statistical
      analysis in the TACT trial found no evidence that pAKT473, pS6 or p90RSK
      identifies patients deriving reduced benefit from adjuvant docetaxel. This result
      is consistent with the recent NASBP B28 study where the pAKT473 effect is not
      statistically significant for the treatment interaction test. Therefore, neither
      TACT nor NASBP-B28 provides statistically robust evidence of a treatment by
      marker interaction between pAKT473 and taxane treatment. Alternative methods for
      selecting patients benefitting from taxanes should be explored.

PMID- 23535840
TI  - Differential role of psoriasin (S100A7) in estrogen receptor alpha positive and
      negative breast cancer cells occur through actin remodeling.
AB  - Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly
      expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive
      breast cancers. However, its role in invasion and metastasis is not very well
      known. In this study, we have shown that S100A7 differentially regulates
      epidermal growth factor (EGF)-induced cell migration and invasion in ERalpha(-)
      MDA-MB-231 cells and ERalpha(+) MCF-7 and T47D breast cancer cells. Further
      signaling studies revealed that S100A7 enhances EGF-induced EGFR phosphorylation
      and actin remodeling that seems to favor lamellipodia formation in ERalpha(-)
      cells. In addition, S100A7 overexpression enhanced NF-kappaB-mediated matrix
      metalloproteinase-9 (MMP-9) secretion in MDA-MB-231 cells indicating its role in
      enhanced invasiveness. However, S100A7 overexpression inhibited migration and
      invasion of MCF-7 cells by inactivating Rac-1 pathway and MMP-9 secretion.
      Moreover, S100A7 overexpressing MDA-MB-231 cells showed enhanced metastasis
      compared to vector control in in vivo nude mice as detected by bioluminescence
      imaging. Our tissue microarray data also revealed predominant expression of
      S100A7 in ERalpha(-) metastatic carcinoma, especially in lymph node regions.
      Overall these studies suggest that S100A7 may enhance metastasis in ERalpha(-)
      breast cancer cells by a novel mechanism through regulation of actin cytoskeleton
      and MMP-9 secretion.

PMID- 23535843
TI  - Ovarian cancer: At the starting line.

PMID- 23535842
TI  - Invasive ductal carcinoma with lobular features: a comparison study to invasive
      ductal and invasive lobular carcinomas of the breast.
AB  - Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a
      distinct subtype of breast cancer, and its clinicopathologic features and
      outcomes are unknown. In this retrospective study, we focused on characterization
      of clinicopathologic features and outcomes of IDC-L and compared them to invasive
      ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L
      from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC.
      Available slides of IDC-L (n = 150) were reviewed to quantify the lobular
      component (<= 20, 21-50, 51-80, >80 %), defined as small cells individually
      dispersed, arranged in linear cords, or in loose aggregates without the formation
      of tubules or cohesive nests. E-cadherin immunostain was performed to confirm
      ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic
      grade (p < 0.001), be positive for estrogen receptor (96 vs. 70 %; p < 0.0001)
      and progesterone receptor (84 vs. 57 %; p < 0.0001), and less likely to
      overexpress HER-2/neu (12 vs. 23 %; p = 0.001). Despite these favorable
      prognostic features, IDC-L had a higher frequency of nodal metastases (51 vs. 34
      %; p < 0.0001) and a worse 5-year disease-free survival than IDC (hazard ratio =
      0.454; p = 0.0004). ILC and IDC-L had similar clinicopathologic features and
      outcomes. The proportion of the lobular component in IDC-L had no impact on the
      size, nodal status, stage, or outcome. Our data suggest that although IDC-L may
      be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical
      and biological characteristics are more similar to that of ILC.

PMID- 23535844
TI  - Leukaemia: 'Gimme shelter'.

PMID- 23535845
TI  - Senescence: ConnectING endocytosis.

PMID- 23535847
TI  - Metastasis: ADORA(2B)tion.

PMID- 23535849
TI  - Radiolabeled anti-aquaporin-4 protein antibody imaging: a valuable method for
      determining neuromyelitis optica.

PMID- 23535848
TI  - When are biomarkers useful in the management of airway diseases?
AB  - Biomarkers are characteristics that are objectively measured and evaluated as
      indicators of biological or pathogenic processes, or responses to therapeutic
      interventions, and may provide information on the prognosis or progression of the
      disease and response to treatment. They are likely to be helpful in the
      management of airway diseases because of the heterogeneity of their pathobiology.
      Most biomarkers have been developed and evaluated to assess the airway
      inflammation (or bronchitis) associated with airway diseases. These include
      quantitative cell counts in sputum, fraction of nitric oxide in exhaled breath,
      and various metabolites in exhaled breath. This review provides a brief
      description of these biomarkers with a particular emphasis on how eosinophil and
      neutrophil counts in sputum could be used to manage airway diseases such as
      asthma, chronic obstructive pulmonary disease, and chronic cough. 

PMID- 23535846
TI  - Plasticity of tumour and immune cells: a source of heterogeneity and a cause for
      therapy resistance?
AB  - Immunotherapies, signal transduction inhibitors and chemotherapies can
      successfully achieve remissions in advanced stage cancer patients, but durable
      responses are rare. Using malignant melanoma as a paradigm, we propose that
      therapy-induced injury to tumour tissue and the resultant inflammation can
      activate protective and regenerative responses that represent a shared resistance
      mechanism to different treatments. Inflammation-driven phenotypic plasticity
      alters the antigenic landscape of tumour cells, rewires oncogenic signalling
      networks, protects against cell death and reprogrammes immune cell functions. We
      propose that the successful combination of cancer treatments to tackle resistance
      requires an interdisciplinary understanding of these resistance mechanisms,
      supported by mathematical models.

PMID- 23535852
TI  - A harbor seal can transfer the same/different concept to new stimulus dimensions.
AB  - We investigated the formation of an abstract concept of same/different in a
      harbor seal by means of a two-item same/different task. Stimuli were presented on
      a TFT monitor. The subject was trained to respond according to whether two
      horizontally aligned white shapes presented on a black background were the same,
      or different from each other, by giving a no-go or go response. Training
      comprised of four stages. First, the same/different task was trained with two
      shapes forming two same problems (A-A and B-B) and two different problems (A-B
      and B-A). After the learning criterion was reached, training proceeded with new
      pairs of shapes. In the second experimental stage, every problem was presented
      just five times before new problems were introduced. We showed that training to
      criterion with just two shapes resulted in item-specific learning, whereas
      reducing the number of presentations to five per problem led to the formation of
      a same/different learning set as well as some restricted relational learning.
      Training with trial-unique problems in the third stage of this study resulted in
      the formation of an abstract concept of same/different which was indicated by a
      highly significant performance in transfer tests with 120 novel problems.
      Finally, extra-dimensional transfer of the concept was tested. The harbor seal
      showed a significantly correct performance on transfer tests with 30 unfamiliar
      pattern and 60 unfamiliar brightness same/different problems, thus demonstrating
      that the concept is not restricted to the shape dimension originally learned, but
      can be generalized across stimulus dimensions. 

PMID- 23535851
TI  - Establishment of a versatile cell line for juvenile hormone signaling analysis in
      Tribolium castaneum.
AB  - The red flour beetle, Tribolium castaneum, has been widely used as a laboratory
      model for analyzing gene function. In this study, we established a novel cell
      line (Tc81) from T. castaneum embryos and validated the utility of this cell line
      by analyzing the juvenile hormone (JH) signaling pathway. In Tc81 cells, the
      Kruppel homolog 1 gene (Kr-h1), which is a JH-dependent repressor of insect
      metamorphosis, was rapidly induced by subnanomolar levels of JHs. Bioinformatics
      analysis and reporter assays identified 2 JH response elements (kJHREs) located
      in the region upstream of the transcription start site and in the first intron of
      Kr-h1. Furthermore, methoprene tolerant (Met) and steroid receptor co-activator
      (SRC) RNAi reduced JH-dependent induction of Kr-h1 transcripts and kJHRE-reporter
      activities. Thus, this novel Tc81 cell line is useful for the elucidation of JH
      signaling and is a promising tool for the functional analysis of genes by RNAi
      and reporter assays.

PMID- 23535853
TI  - The effect of heat acclimation on sweat microminerals: artifact of surface
      contamination.
AB  - Heat acclimation (HA) reportedly conveys conservation in sweat micromineral
      concentrations when sampled from arm sweat, but time course is unknown. The
      observation that comprehensive cleaning of the skin surface negates sweat
      micromineral reductions during prolonged sweating raises the question of whether
      the reported HA effect is real or artifact of surface contamination. PURPOSE: To
      measure sweat mineral concentrations serially during HA and determine if surface
      contamination plays a role in the reported mineral reductions. METHODS: Calcium
      (Ca), copper (Cu), magnesium (Mg), and zinc (Zn) were measured in sweat obtained
      from 17 male volunteers using an arm bag on Day 1, 5, and 10 of a HA protocol. To
      study the role of contamination, sweat was simultaneously (n = 10 subjects)
      sampled twice daily from a cleaned site (WASH) and unclean site (NO WASH) on the
      scapular surface. RESULTS: Sweat Ca, Cu, and Mg from Arm Bag trended
      progressively downward from Day 1 to Day 10 of HA (p = .10-0.25). Micromineral
      concentrations from the WASH site did not change between Day 1, 5, or 10 (Ca =
      0.30 +/- 0.12 mmol/L, Cu 0.41 +/- 0.53 MUmol/L; Zn 1.11 +/- 0.80 MUmol/L).
      Surface contamination can confound sweat mineral estimates, as sweat Ca and Cu
      from NO WASH site were initially higher than WASH (p < .05) but became similar to
      WASH when sampled serially. CONCLUSION: Heat acclimation does not confer
      reductions in sweat Ca, Cu, Mg, or Zn. When the skin surface is not cleaned,
      mineral residue inflates initial sweat mineral concentrations. Earlier reports of
      micromineral reductions during HA may have been confounded by interday cleaning
      variability.

PMID- 23535854
TI  - Supramolecular bulky phosphines comprising 1,3,5-triaza-7-phosphaadamantane and
      Zn(salphen)s: structural features and application in hydrosilylation catalysis.
AB  - The use of the commercially available, bifunctional phosphine 1,3,5-triaza-7
      phosphaadamantane (abbreviated as PN3) in conjunction with a series of
      Zn(salphen) complexes leads to sterically encumbered phosphine ligands as a
      result of (reversible) coordinative Zn-N interactions. The solid state and
      solution phase behaviour of these supramolecular ligand systems have been
      investigated in detail and revealed their stoichiometries in the solid state
      observed by X-ray crystallography, and those determined in solution by NMR and UV
      Vis spectroscopy. Also, upon application of these supramolecular bulky phosphines
      in hydrosilylation catalysis employing 1-hexene as a substrate, the catalysis
      data infer the presence of an active Rh species with two coordinated, bulky
      PN3/Zn(salphen) assembly units having a maximum of three Zn(salphen)s associated
      per PN3 scaffold, with an excess of bulky phosphines hardly affecting the overall
      activity.

PMID- 23535856
TI  - Impact factor and study quality.

PMID- 23535855
TI  - Physical and psychosocial support requirements of 1,500 patients starting
      radiotherapy.
AB  - BACKGROUND: The need for psychosocial support in cancer patients is estimated in
      the literature at 14-50 %. At the Department of Radiation Oncology, Medical
      University of Vienna, approximately 3,000 patients are seen annually. Due to
      limited staff resources, highly distressed patients need to be selected for
      focused support. A multidisciplinary screening questionnaire covering physical,
      social and psychological problems and needs was successfully implemented in
      clinical routine. We present the results of a representative sample of 1,500
      heterogeneous cancer patients before beginning radiotherapy. PATIENTS AND
      METHODS: The prevalence rates of physical, social and psychological problems and
      needs were evaluated. Independent risk factors for critical psychological
      distress were analyzed in a multivariate logistic regression model, in order to
      identify vulnerable subgroups for focused psychosocial support. RESULTS: Critical
      psychological distress was found in 22 % of the overall cohort, of whom only 26 %
      reported a need for psychological information. Clinically relevant pain was
      suffered by 31 %. Patients' most frequent complaints were weakness, sleeping
      difficulties and exhaustion. Consequently, 40 % were impaired in activities and
      35 % reported a requirement for support in daily life. A need for further
      information was expressed by 37 % of patients. Significant risk factors for
      critical psychological distress included pain, functional status, support
      requirements and patient-reported symptoms. Differences in tumor type, metastases
      and sociodemographic variables had no impact on critical psychological distress.
      CONCLUSION: Approximately one third of all patients beginning radiotherapy have
      physical, social and psychological problems and should receive focused
      psychosocial support. Multivariate analysis reveals that patients with impaired
      "physical integrity" are at a significantly higher risk of experiencing critical
      psychological distress.

PMID- 23535857
TI  - Can daily multivitamin prevent cancer? Results from the Physicians' Health Study.

PMID- 23535858
TI  - Encapsulating peritoneal sclerosis.

PMID- 23535859
TI  - Co-occurrence of hepatocellular cancer and non-Hodgkin lymphoma.

PMID- 23535860
TI  - Hashimoto's thyroiditis associated with idiopathic portal hypertension.

PMID- 23535861
TI  - Comment on "Coronary artery calcium in type 2 diabetes: a nested case-control
      study".

PMID- 23535862
TI  - Comment on "Coronary artery calcium in type 2 diabetes: a nested case-control
      study": authors' reply.

PMID- 23535863
TI  - Low temperature phase selective synthesis of Cu(2)ZnSnS(4) quantum dots.
AB  - The application of indium-free quaternary chalcogenides, such as Cu(2)ZnSnS(4)
      (CZTS), in photovoltaics has created tremendous interest in recent years. In this
      paper we develop a method to synthesize high quality CZTS nanoparticles with
      thermodynamically stable kesterite and wurtzite phases via a simple, one-pot, low
      cost solution method.

PMID- 23535864
TI  - Intrinsic bias and public rearrangements in the human immunoglobulin Vlambda
      light chain repertoire.
AB  - The immunoglobulin lambda (IGL) repertoires from two unrelated human blood
      samples, three NOD-scid-IL2Rgamma(null) mice engrafted with human hematopoietic
      stem cells and two pairs of monozygotic twin blood samples were determined by
      Roche 454 sequencing to generate a total of about 700 000 IGL sequences. We
      applied bioinformatic analysis to examine IGL repertoires wherein, surprisingly,
      ?20% of CDR-L3 peptide sequences were 'public' (shared across individuals);
      moreover, full-length IGL protein sequences (VJ recombinants) were also present
      in the public domain. Subtle yet significant differences in CDR-L3 nontemplated
      nucleotide addition, IGL V-gene family usage, and amino-acid composition
      distinguished the public CDR-L3 groups from the private groups. These data
      suggest that public CDR-L3 intervals can arise by intrinsic genetic mechanisms
      irrespective of different B-cell developmental milieu (human versus humanized
      mouse). Furthermore, the occurrence of identical public IGL protein sequences
      indirectly suggest the positive selection (evolutionary, somatic or both) of
      particular IGL chains independent of the immunoglobulin heavy chain.

PMID- 23535865
TI  - Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility.
AB  - The type I interferon system genes IKBKE and IFIH1 are associated with the risk
      of systemic lupus erythematosus (SLE). To identify the sequence variants that are
      able to account for the disease association, we resequenced the genes IKBKE and
      IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional
      effect or differences in allele frequencies between patients and controls
      determined by sequencing were further genotyped in 1140 SLE patients and 2060
      controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were
      included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were
      associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent
      association signals in IKBKE, and the haplotype carrying their risk alleles
      showed an odds ratio of 1.68 (P-value=1.0 * 10(-5)). The risk allele of
      rs12142086 affects the binding of splicing factor 1 in vitro and could thus
      influence its transcriptional regulatory function. Two independent association
      signals were also detected in IFIH1, which were tagged by a low-frequency SNV
      rs78456138 and a missense SNV rs3747517. Their joint effect is protective against
      SLE (odds ratio=0.56; P-value=6.6 * 10(-3)). In conclusion, we have identified
      new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional
      hypotheses for the association signals.

PMID- 23535866
TI  - A birth cohort analysis of the incidence of ascending and descending colon cancer
      in the United States, 1973-2008.
AB  - OBJECTIVES: There is evidence indicating that the trends in colorectal cancer
      (CRC) incidence rates in the United States differ according to CRC subsites,
      including for ascending cancer which has shown a different pattern from the
      overall trends. We investigated the time trends for ascending and descending
      colon cancer in the United States by race and gender to identify the specific
      components that may account for the incidence trends. METHODS: Using data from
      the National Cancer Institute's Surveillance, Epidemiology, and End Results
      program for 1973-2008, we conducted age-period-cohort modeling to evaluate birth
      cohort patterns and evaluate age-period-cohort effects on incidence trends of
      colon cancer over time. RESULTS: A clear birth cohort pattern was observed for
      both ascending and descending colon cancer, and the incidence rates of ascending
      colon cancer in the more recent birth cohorts were higher compared to earlier
      cohorts particularly for black males and females. This increase was most obvious
      in the younger age groups and appeared to accelerate, especially for black
      females. For descending colon cancer, the study suggested an increase in the
      birth cohort slope in the later birth cohorts for all gender and race groups,
      after a period of decline in earlier birth cohorts. CONCLUSION: The increase in
      incidence rates of both ascending and descending colon cancer in more recent
      birth cohorts for blacks suggests the need for targeted public health strategies
      to increase CRC screening. Further, additional etiological studies are warranted
      to evaluate factors responsible for the observed trends in more recent birth
      cohorts, including differences by subsites, race, and/or gender.

PMID- 23535867
TI  - Consumption of fruit, vegetables, and other food groups and the risk of
      nasopharyngeal carcinoma.
AB  - PURPOSE: The role of dietary habits in the etiology of nasopharyngeal carcinoma
      (NPC) has been extensively investigated in high-incidence areas, but evidence is
      scanty in low-incidence populations. This study aimed to investigate the
      relationship between NPC risk and a wide range of food groups in the Italian
      population. METHODS: We conducted a hospital-based case-control study in Italy on
      198, histologically confirmed, NPC cases of Caucasian ethnicity, aged 18-76
      years. Controls were 594 Caucasian cancer-free patients admitted to general
      hospitals for acute conditions. Odds ratios (ORs) and the corresponding
      confidence intervals (CIs) were estimated through logistic regression, adjusting
      for socio-demographic characteristics, tobacco smoking, alcohol drinking, and
      energy intake. RESULTS: Elevated vegetable consumption was inversely related to
      NPC risk (OR for highest vs. lower quartile = 0.51; 95 % CI 0.29-0.90). The
      association was particularly strong for yellow- or red-pigmented vegetables (OR =
      0.31; 95 % CI 0.18-0.54), and this effect was stronger among never smokers (OR =
      0.18; 95 % CI 0.06-0.55) than among ever smokers (OR = 0.37; 95 % CI 0.19-0.71).
      Increased NPC risk emerged for elevated eggs consumption (OR = 2.50; 95 % CI 1.44
      4.32; p-trend <0.01). No significant associations emerged between NPC risk and
      consumption of cereals, meat, fish, dairy products, and sweets. CONCLUSIONS: The
      study findings show that, also in low-risk populations, vegetable consumption is
      a protective factor against NPC. The stronger effect for yellow- or red-pigmented
      vegetables is in agreement with the inverse association reported for carotenoids
      intake.

PMID- 23535868
TI  - A chimeric cry8Ea1 gene flanked by MARs efficiently controls Holotrichia
      parallela.
AB  - KEY MESSAGE: Peanuts transformed with the synthetic cry8Ea1 gene flanked by MARs
      are a potentially effective control strategy against white grubs. Cry8Ea1 protein
      levels of the construct containing MARs were increased by 2.5 times. White grubs
      are now recognized as the most important pests of peanut worldwide. A synthetic
      cry8Ea1 gene, which was toxic to Holotrichia parallela larvae, was expressed in
      chimeric peanut roots using an Agrobacterium rhizogenes-mediated transformation
      system. The relative mRNA and protein levels of the cry8Ea1 gene were confirmed
      by quantitative real-time PCR and ELISA, respectively. The effects of matrix
      attachment regions (MARs) on the expression and activity of the cry8Ea1 gene were
      analyzed. The average expression level of cry8Ea1 in peanut roots was higher for
      the plants harboring constructs flanked by MARs from tobacco. Moreover, differing
      from previous studies, the synthetic cry8Ea1 gene flanked by MARs showed more
      variation in protein levels than mRNA levels. These composite plants containing
      cry8Ea1 gene flanked by MARs exhibited a high toxicity against Holotrichia
      parallela larvae as shown by bioassay analysis, thus offering a potential
      effective combination to control subterranean insects in peanuts.

PMID- 23535869
TI  - ABA signaling in stress-response and seed development.
AB  - KEY MESSAGE : We review the recent progress on ABA signaling, especially ABA
      signaling for ABA-dependent gene expression, including the AREB/ABF regulon,
      SnRK2 protein kinase, 2C-type protein phosphatases and ABA receptors. Drought
      negatively impacts plant growth and the productivity of crops. Drought causes
      osmotic stress to organisms, and the osmotic stress causes dehydration in plant
      cells. Abscisic acid (ABA) is produced under osmotic stress conditions, and it
      plays an important role in the stress response and tolerance of plants. ABA
      regulates many genes under osmotic stress conditions. It also regulates gene
      expression during seed development and germination. The ABA-responsive element
      (ABRE) is the major cis-element for ABA-responsive gene expression. ABRE-binding
      protein (AREB)/ABRE-binding factor (ABF) transcription factors (TFs) regulate
      ABRE-dependent gene expression. Other TFs are also involved in ABA-responsive
      gene expression. SNF1-related protein kinases 2 are the key regulators of ABA
      signaling including the AREB/ABF regulon. Recently, ABA receptors and group A 2C
      type protein phosphatases were shown to govern the ABA signaling pathway.
      Moreover, recent studies have suggested that there are interactions between the
      major ABA signaling pathway and other signaling factors in stress-response and
      seed development. The control of the expression of ABA signaling factors may
      improve tolerance to environmental stresses.

PMID- 23535870
TI  - Controlling potassium selectivity and proton blocking in a hybrid
      biological/solid-state polymer nanoporous membrane.
AB  - Specific separations of protons and cations are usually performed by
      electromembrane processes, which require external electric energy. An easier
      process would be using a membrane able to separate both entities by passive
      diffusion. Presently, such synthetic nanoporous membranes do not exist. Here, we
      report the production of a robust hybrid biological/artificial solid-state
      membrane, which allows selective permeation of alkali metal cations without
      competing or concurrent permeation of protons. This membrane is simple to prepare
      and is based on the hydrophobic nature of the polymeric pore walls, and the
      confined gramicidin A molecules within. This work opens a new route for
      separation in the domain of nanobiofiltration, especially for tunable nanodevices
      based on differential ion conduction, with a fundamental understanding of the
      confinement mechanism.

PMID- 23535871
TI  - MG132-mediated inhibition of the ubiquitin-proteasome pathway ameliorates cancer
      cachexia.
AB  - PURPOSE: To evaluate the effect of proteasome inhibitor MG132 in cancer cachexia
      and to delineate the molecular mechanism underlying. METHODS: We established an
      experimental cancer cachexia model by subcutaneously implanting colon 26 cells
      into the armpits of BALB/c mice. Following administration of MG132 at various
      time points, body weight, food intake, gastrocnemius muscle weight, spontaneous
      activity and survival of tumor-bearing mice were examined along with tumor
      growth. Moreover, cachectic markers including glucose, triglyceride, albumin and
      total proteins as well as levels of the proinflammatory cytokines TNF-alpha and
      IL-6 in serum and gastrocnemius tissue were measured. Finally, mRNA and protein
      levels of p65, IkappaBalpha, and ubiquitin E3 ligases MuRF1 and MAFbx in
      gastrocnemius muscle were assessed. RESULTS: MG132 treatment significantly
      alleviated cancer cachexia as demonstrated by attenuated weight loss, altered
      carbohydrate metabolism and muscle atrophy and increased spontaneous activity and
      survival time of tumor-bearing mice. MG132 reduced tumor growth and the levels of
      TNF-alpha and IL-6 in serum and gastrocnemius tissue. NF-kappaB, MuRF1 and MAFbx
      were also inhibited by MG132. Unexpectedly, MG132 was more efficient when
      administrated during the early stages of cachexia. MG132 had no effect on food
      intake of tumor-bearing mice. CONCLUSION: Our results demonstrate that MG132
      induced inhibition of the ubiquitin-proteasome pathway in cancer cachexia
      decreased the activity of NF-kappaB and the degradation of IkappaBalpha, and
      reduced the levels of TNF-alpha and IL-6 in serum and gastrocnemius tissue,
      accompanied by downregulation of MuRF1 and MAFbx. These data suggest that MG132
      is a potential therapeutic and preventive agent for cancer cachexia.

PMID- 23535872
TI  - The effect of preimplantation genetic screening on neurological, cognitive and
      behavioural development in 4-year-old children: follow-up of a RCT.
AB  - STUDY QUESTION: Does embryo biopsy inherent to preimplantation genetic screening
      (PGS) affect neurological, cognitive and behavioural development of 4-year-old
      children? SUMMARY ANSWER: PGS does not seem to affect neurological, cognitive and
      behavioural development of 4-year-old singletons; however, our data suggest that
      it may be associated with altered neurodevelopment in twins. WHAT IS KNOWN
      ALREADY: Evidence concerning the safety of PGS on neurodevelopmental outcome in
      offspring is scarce. The present study provides information on
      neurodevelopmental, cognitive and behavioural outcome of 4-year-old PGS
      offspring. STUDY DESIGN, SIZE, DURATION: A prospective, assessor-blinded follow
      up study of children born to women who participated in a multi-centre RCT on the
      effect of IVF with or without PGS. PARTICIPANTS/MATERIALS, SETTING, METHODS: At 4
      years, 49 children (31 singletons, 9 sets of twins) born following IVF with PGS
      and 64 children (42 singletons, 11 sets of twins) born following IVF without PGS
      (controls) were assessed (post-natal attrition 18%). Neurological development was
      evaluated with the standardized, age-specific and sensitive neurological
      examination according to Hempel, resulting in a neurological optimality score
      (NOS), a fluency score and the rate of adverse neurological outcome. Primary
      outcome was the fluency score, as fluency of movements is easily reduced by
      subtle dysfunction of the brain. Cognitive development was evaluated with the
      Kaufman Assessment Battery for Children; behavioural development was evaluated
      with the Child Behavior Checklist. The effect of PGS was analysed with a mixed
      effects model. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the intention to
      treat analysis, neurodevelopmental outcome of PGS children was similar to that of
      controls. However, additional analyses indicated that PGS affected
      neurodevelopmental outcome of twins in a different way than that of singletons.
      The fluency score of singletons born following PGS was similar to that of control
      singletons [mean values, 95% confidence intervals (CIs): 12.2 (11.5;12.8) and
      12.2 (11.6;12.8)], respectively, P = 0.977) that was also true for the other
      neurodevelopmental parameters. The fluency score of PGS twins was significantly
      lower than that of control twins [mean values, 95% CIs: 10.6 (9.8;11.3) and 12.3
      (11.5;13.1)], respectively, P = 0.001); the same was true for the NOS. In
      addition, PGS in twins was associated with a higher sequential intelligence
      quotient score. On the other hand, other neurodevelopmental parameters were
      similar for PGS twins and control twins. Post hoc sample size calculation for the
      primary outcome parameter, the fluency score, indicated that the study groups,
      including the subgroups of singletons and twins, were adequately powered.
      LIMITATIONS, REASONS FOR CAUTION: We assessed singletons and twins who
      contributed to the generalizability of the study. A limitation of our study is
      the relative small size of our study groups and the selective dropout in both
      groups (dropouts PGS group: higher gestational age; control group: less well
      educated parents). These preclude the conclusion that PGS per se is not
      associated with neurodevelopmental, cognitive and behavioural problems in
      singletons and the conclusion that PGS is associated with altered
      neurodevelopmental outcome in twins. WIDER IMPLICATIONS OF THE FINDINGS: The need
      for careful long-term monitoring of children born following embryo biopsy
      remains, as it is still applied in the form of PGD and it is still unknown
      whether embryo biopsy affects long-term neurodevelopmental outcome.

PMID- 23535874
TI  - Hyperconjugation involving strained carbon-carbon bonds. Application of the
      variable oxygen probe to ester and ether derivatives of cubylmethanol.
AB  - Application of the variable oxygen probe to derivatives of (4
      methoxycarbonyl)cubylmethanol 11 demonstrated a strong response of C-OR bond
      distance to the electron demand of the OR substituent, consistent with an
      enhanced sigma-donor ability of the strained C-C bonds of cubane. The extent of
      cubane donor ability was found to be superior to an unstrained donor 13,
      comparing data extracted from the Cambridge Structural Database (T. W. Cole,
      Ph.D. Dissertation, University of Chicago, 1966), but weaker than the previously
      studied cyclopropane donors. Structural evidence is also found for sigmaCC-pi*CO
      interactions in these structures.

PMID- 23535873
TI  - Effect of beta-alanine, with and without sodium bicarbonate, on 2000-m rowing
      performance.
AB  - PURPOSE: To examine the effect of beta-alanine only and beta-alanine with sodium
      bicarbonate supplementation on 2,000-m rowing performance. METHODS: Twenty well
      trained rowers (age 23 +/- 4 y; height 1.85 +/- 0.08 m; body mass 82.5 +/- 8.9
      kg) were assigned to either a placebo or beta-alanine (6.4 g . d(-1) for 4 weeks)
      group. A 2,000-m rowing time trial (TT) was performed before supplementation
      (Baseline) and after 28 and 30 days of supplementation. The post supplementation
      trials involved supplementation with either maltodextrin or sodium bicarbonate in
      a double-blind, crossover design, creating four study conditions (placebo with
      maltodextrin; placebo with sodium bicarbonate; beta-alanine with maltodextrin;
      beta-alanine with sodium bicarbonate). Blood lactate, pH, bicarbonate, and base
      excess were measured pre-TT, immediately post-TT and at TT+5 min. Performance
      data were analyzed using magnitude based inferences. RESULTS: Beta-alanine
      supplementation was very likely to be beneficial to 2,000-m rowing performance
      (6.4 +/- 8.1 s effect compared with placebo), with the effect of sodium
      bicarbonate having a likely benefit (3.2 +/- 8.8 s). There was a small (1.1 +/-
      5.6 s) but possibly beneficial additional effect when combining chronic beta
      alanine supplementation with acute sodium bicarbonate supplementation compared
      with chronic beta-alanine supplementation alone. Sodium bicarbonate ingestion led
      to increases in plasma pH, base excess, bicarbonate, and lactate concentrations.
      CONCLUSIONS: Both chronic beta-alanine and acute sodium bicarbonate
      supplementation alone had positive effects on 2,000-m rowing performance. The
      addition of acute sodium bicarbonate to chronic beta-alanine supplementation may
      further enhance rowing performance.

PMID- 23535875
TI  - Tailoring dispersion for broadband low-loss optical metamaterials using deep
      subwavelength Inclusions.
AB  - Metamaterials have the potential to create optical devices with new and diverse
      functionalities based on novel wave phenomena. Most practical optical systems
      require that the device properties be tightly controlled over a broad wavelength
      range. However, optical metamaterials are inherently dispersive, which limits
      operational bandwidths and leads to high absorption losses. Here, we show that
      deep-subwavelength inclusions can controllably tailor the dispersive properties
      of an established metamaterial structure thereby producing a broadband low-loss
      optical device with a desired response. We experimentally verify this by
      optimizing an array of nano-notch inclusions, which perturb the mode patterns and
      strength of the primary and secondary fishnet nanostructure resonances and give
      an optically thin mid-wave-infrared filter with a broad transmissive pass-band
      and near-constant group delay. This work outlines a powerful new strategy for
      realizing a wide range of broadband optical devices that exploit the unique
      properties of metamaterials.

PMID- 23535876
TI  - Physician recommendations and patient adherence after inadequate bowel
      preparation on screening colonoscopy.
AB  - BACKGROUND AND AIMS: It has been suggested that bowel preparation quality may
      influence decision-making about appropriate follow-up interval after screening
      colonoscopy. We sought: (1) to assess physician recommendations for timing of
      subsequent colonoscopy in average-risk patients with inadequate bowel preparation
      on initial screening, and (2) to measure the association between physician
      recommendations and patient adherence to repeat colonoscopy. METHODS: Patients
      undergoing average-risk screening colonoscopy from 2004 to 2009 found to have
      inadequate bowel preparation were identified. Physician recommendations for
      timing of subsequent colonoscopy and patient adherence to repeat colonoscopy were
      assessed through examination of endoscopy records. Data from repeat colonoscopies
      were collected through August 2010. RESULTS: There were 373 patients with
      inadequate bowel preparation on initial screening colonoscopy. There was a wide
      range of physician recommendations for timing of repeat colonoscopy: next day
      (4.6 % of patients), 2 days to 6 months (9.9 %), 7 months to 1 year (34.0 %), 2-5
      years (38.3 %), 6-10 years (5.1 %), and timing not specified (8.0 %). Physicians
      were significantly more likely to recommend repeat colonoscopy within 1 year if
      any polyps were detected (OR = 2.2, p = 0.001). Patients instructed to have next
      day follow-up were significantly more likely to adhere to the recommendation
      compared to patients who were instructed to return after longer intervals (OR
      4.4, p = 0.005). CONCLUSIONS: Patients with inadequate bowel preparation on
      screening colonoscopy were subject to a wide range of physician recommendations
      for follow-up. Patient adherence to physician recommendations was significantly
      higher when repeat colonoscopy was recommended the next day.

PMID- 23535877
TI  - Endoscopic ultrasound-guided antegrade treatments for biliary disorders in
      patients with surgically altered anatomy.
AB  - INTRODUCTION: Endoscopic retrograde cholangiopancreatography in patients with
      surgically altered anatomy is challenging. Several endoscopic ultrasound (EUS)
      guided biliary access techniques have been reported as effective alternatives.
      EUS-guided antegrade treatments (AG) have been developed more recently but have
      not yet been studied well. AIMS: To evaluate the feasibility and safety of EUS-AG
      for biliary disorders in patients with surgically altered anatomies. METHODS: We
      retrospectively identified all the patients who underwent EUS-AG. The left
      intrahepatic bile duct (IHBD) was initially punctured from the intestine followed
      by cholangiography, antegrade guidewire manipulation, and bougie dilation of the
      fistula. Either antegrade biliary stenting (ABS) or antegrade balloon dilation
      (ABD) was performed depending on the biliary disorders. In stone cases, the
      stones were antegradely pushed out using a balloon. After ABD, a nasobiliary
      drainage tube was placed to prevent possible bile leak and to keep an access
      route for any possible repeat procedures. RESULTS: EUS-AG was attempted in seven
      patients including choledocholithiasis in five, malignant biliary obstruction in
      one, and bilioenteric anastomosis stricture in one. EUS-AG was not performed in
      one patient because EUS-cholangiography did not indicate the presence of stones.
      In the remaining six patients, the IHBD was successfully punctured, followed by
      cholangiography, guidewire insertion, and bougie dilation. ABS and ABD were
      successfully performed in one and five patients, respectively. Antegrade
      procedures with ABD were repeated twice in one patient. Mild complications were
      observed in two patients. CONCLUSIONS: EUS-AG for biliary disorders in patients
      with surgically altered anatomy is feasible. Further studies are warranted.

PMID- 23535878
TI  - Celiac disease: clinch the diagnosis when it is just around the corner.

PMID- 23535879
TI  - Transplacental passage of etravirine and maraviroc in a multidrug-experienced HIV
      infected woman failing on darunavir-based HAART in late pregnancy.

PMID- 23535880
TI  - Prevalence of mupirocin resistance among invasive coagulase-negative
      staphylococci and methicillin-resistant Staphylococcus aureus (MRSA) in France:
      emergence of a mupirocin-resistant MRSA clone harbouring mupA.
AB  - OBJECTIVES: Mupirocin is the cornerstone of decolonization regimens, a successful
      strategy to prevent healthcare-associated staphylococcal infections. Several
      recent studies have reported alarming results: (i) an extending reservoir of
      mupA, the ancestral mobile resistance gene, among coagulase-negative
      staphylococci (CoNS); (ii) the emergence of a new resistance gene (mupB); and
      (iii) a growing number of mupirocin-resistant methicillin-resistant
      Staphylococcus aureus (MRSA), including highly pathogenic clones. We performed a
      nationwide prospective study in France to detect such trends among invasive
      staphylococci. METHODS: Between October 2011 and February 2012, 367 MRSA and 708
      CoNS invasive isolates were collected from 37 hospitals and analysed centrally.
      Mupirocin MICs were determined using the broth microdilution method. mupA/B PCR
      was performed for resistant isolates (MIC >1 mg/L). Genetic relatedness between
      mupirocin-resistant MRSA isolates was determined by PFGE analysis and related
      isolates were tested by microarray. RESULTS: Among MRSA isolates 2.2% (n = 8)
      were classified as mupirocin resistant; 1.4% (n = 5) showing low-level resistance
      (MIC <=256 mg/L) and 0.8% (n = 3) high-level resistance (MIC >256 mg/L). Only the
      latter isolates carried mupA. A clonal relationship was identified between two
      mupA-negative MRSA from the same hospital and three mupA-positive MRSA from three
      distant towns; these three isolates belonged to the Lyon clone. Mupirocin
      resistance was identified in 10.3% of CoNS, mainly highly resistant mupA-positive
      isolates (5.6%). The mupB gene was not detected in mupirocin-resistant MRSA or
      CoNS. CONCLUSIONS: This first large national study indicates the need for
      thorough epidemiological monitoring and a stewardship programme to prevent and
      detect mupirocin resistance in staphylococci.

PMID- 23535881
TI  - Mixed bloodstream infections involving bacteria and Candida spp.
AB  - OBJECTIVES: Polymicrobial bloodstream infection (BSI) is an imprecisely defined
      entity purportedly associated with a worse outcome than monomicrobial BSI. This
      study examines trends in BSI episodes caused by bacteria and Candida spp. (mixed
      BSI) in a large teaching hospital. METHODS: All episodes of BSI from January 2000
      to December 2010 were reviewed. Three groups (n = 54 each) of patients were
      compared: all adults with mixed-BSI from January 2006 to December 2010 (cases)
      and randomly selected patients with polybacterial BSI (polyB-BSI) (Control 1) or
      Candida spp. BSI (Candida-BSI) (Control 2) in this same period. RESULTS: A total
      of 139 episodes of mixed-BSI were recorded (0.7% of all BSI, 6.9% of all poly-BSI
      and 18.0% of all Candida-BSI episodes). The incidence of mixed-BSI was 0.21
      cases/1000 admissions, increasing from 0.08 (2000) to 0.34 (2010) cases/1000
      admissions (P = 0.007). Mixed-BSI represented 11.8% and 22.9% of all episodes of
      candidaemia in 2000 and 2010, respectively (P = 0.011). Compared with polyB-BSI,
      mixed-BSI patients showed fewer malignancies, more frequent nosocomial or
      intravenous catheter BSI source and less frequent intra-abdominal origin, were
      more frequently admitted to an intensive care unit (ICU), received more
      antimicrobials and showed a longer hospital stay and higher mortality. Compared
      with Candida-BSI, mixed-BSI patients showed more severe underlying diseases, were
      more frequently admitted to an ICU or oncology-haematology unit, showed a higher
      APACHE II score, more often progressed to septic shock or multiorgan failure and
      received more antimicrobials. Mortality was similar. CONCLUSIONS: Mixed-BSI is a
      rare, distinct infection with a worse prognosis than polyB-BSI. We were unable to
      detect differences in the prognosis of mixed-BSI when compared with Candida-BSI.

PMID- 23535882
TI  - Clinical assessment of the efficacy of SpineCor brace in the correction of
      postural deformities in the course of idiopathic scoliosis.
AB  - BACKGROUND: The objective of the study was to perform a clinical, comparative
      assessment of the degree of postural deformities before and after the treatment
      of idiopathic scoliosis in patients treated with SpineCor brace compared to the
      control group. MATERIAL AND METHODS: A group of 90 children with idiopathic
      scoliosis (including 74 girls) at the average age of 12.2 was subject to
      prospective observation. Average pre-treatment Cobb angle was 24.9 degrees  in
      the thoracic spine and 25.8 degrees  in the lumbar spine. The group actively
      treated with the SpineCor brace consisted of 45 children, while the control group
      consisted of the remaining 45 children with the natural course of the disease.
      RESULTS: Both groups did not differ significantly in terms of age, gender,
      height, body weight, Risser sign of skeletal maturity and baseline clinical and
      radiological parameters of scoliosis. Significant reduction of rib hump was
      observed upon 2-year SpineCor brace treatment (P=0.04) compared to the group
      treated by physiotherapy only (P=0.91). Similarly, improvement in lumbar
      prominence was observed in the actively treated group (P=0.009), with a trend
      towards worse results in the control group (P=0.07) In the group treated with the
      SpineCor brace, significant reduction in pectoral and hamstring muscle
      contractures as well as reduction in shoulder asymmetry and reduction in anterior
      and posterior vertical deviation were observed. CONCLUSIONS: Treatment using the
      SpineCor dynamic brace leads to a clinical improvement in posture, particularly
      to reduction in rib hump, lumbar prominence and muscular contractures.

PMID- 23535883
TI  - Geographical differences in the prevalence of chronic polypharmacy in older
      people: eleven years of the EPIFARM-Elderly Project.
AB  - PURPOSE: To compare the geographical differences in the prevalence of chronic
      polypharmacy in community-dwelling older people over 11 years. METHODS: This
      study analyzed nearly two million patients aged 65-94 years recorded in the Drug
      Administrative Database of the Lombardy Region (Northern Italy) from 2000 to
      2010. Chronic polypharmacy was defined as taking five or more drugs in 1 month
      for at least 6 months (consecutive or not) in a year. RESULTS: There was a
      significant spatial autocorrelation that increased at the municipality level from
      2000 (Moran's I Index = 0.26, z score = 16.91, p < 0.0001) to 2010 (Moran's I
      Index = 0.36, z score = 23.78, p < 0.0001). Clusters of high (Z(G) > 1.96) and
      low (Z(G) < -1.96) prevalence rates of chronic polypharmacy were found and were
      not influenced by age. Chronic polypharmacy weakly correlated with hospital
      admission (2000: rho = 0.08, p = 0.0032; 2005: rho = 0.11, p < 0.0001; 2010: rho
      = 0.18, p < 0.0001), but not with mortality. CONCLUSIONS: There were geographical
      differences in the prevalence of older people with chronic polypharmacy that were
      only partly explained by health indicators. Targeted activities on prescription
      practice to ensure that the prescribing of chronic polypharmacy is appropriate
      are required.

PMID- 23535884
TI  - Synthesis of sterically hindered xanthene-modified iron corroles with catalase
      like activity.
AB  - An up to 18-fold increase of the turnover frequency (TOF) in the catalase-like
      hydrogen peroxide dismutation reaction is observed by incorporation of
      substituents in the beta-position of xanthene-modified iron corroles.

PMID- 23535885
TI  - Porous microspheres of MgO-patched TiO2 for CO2 photoreduction with H2O vapor:
      temperature-dependent activity and stability.
AB  - A novel MgO-patched TiO2 microsphere photocatalyst demonstrated 10 times higher
      activity toward CO production from CO2 photoreduction with H2O vapor, when the
      reaction temperature increased from 50 to 150  degrees C. The catalytic
      performance of hybrid MgO-TiO2 was much more stable than TiO2, particularly at a
      higher temperature, likely due to easier desorption of reaction intermediates and
      the enhanced CO2 adsorption by MgO.

PMID- 23535886
TI  - The CNT modified white C3N4 composite photocatalyst with enhanced visible-light
      response photoactivity.
AB  - A novel, multi-walled carbon nanotubes (CNT) modified white C3N4 composite
      (CNT/white C3N4) with enhanced visible-light-response photoactivity was prepared.
      The white C3N4 and CNT combined together and formed the CNT/white C3N4 composite
      due to electrostatically-driven self-assembly with the hydrothermal method. The
      as-prepared white C3N4 and CNT/white C3N4 composite photocatalyst were
      characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD),
      Fourier transform infrared spectroscopy (FT-IR), UV-vis absorption spectra, X-ray
      photoelectron spectroscopy (XPS) and photoluminescence spectroscopy (PL). The
      photoelectrochemical i-t curves were tested using several on-off cycles of light
      irradiation. The photoactivity of the catalysts was evaluated by degrading
      methylene blue (MB) dye solution. The results showed that the photoactivity for
      the degradation of MB solution was in the following order: CNT/white C3N4
      composite > C3N4 > the white C3N4. The photoactivity of the CNT/white C3N4
      composite was 66.5% and 34.5% higher than that of the white C3N4 sample and that
      of the C3N4 at 1.5 h, respectively. The degradation rate of the CNT/white C3N4
      photocatalyst was almost 8.1 times as high as that of the white C3N4. The results
      indicated that CNT played an important role, which led to the efficient
      separation of the photo-generated charge carriers. The reason why the
      photoactivity of the CNT/white C3N4 was much higher than that of C3N4 and the
      white C3N4 was discussed. A possible mechanism of CNT on the enhancement of
      composites' visible light performance was also proposed.

PMID- 23535887
TI  - Molecular investigations of Hepatozoon species in dogs and developmental stages
      of Rhipicephalus sanguineus.
AB  - The occurrence and distribution of Hepatozoon species in stray dogs, and the
      developmental stages of Rhipicephalus sanguineus detached from the same dogs in
      Diyarbakir Province, Turkey is reported. A total of 328 ticks, including 133
      adults (55 males and 75 females consist of 63 partially engorged and 15 fully
      engorged) and 195 nymphs (91 partially engorged and 104 fully engorged) were
      detached from the dogs. Fully engorged nymphs and females were incubated at 27 
      degrees C and relative humidity of 85 % to molt to adult stage and recover eggs.
      The ticks were pooled according to sex and developmental stage. No Hepatozoon
      gamonts were found, whereas, by PCR, 15.87 % (10/63) of the dogs were infected
      with Hepatozoon canis. Of the 68 tick pools tested, 14 (20.58 %) pools were
      infected with Hepatozoon spp., an overall maximum likelihood estimation of
      prevalence of 4.9 % (95 % confidence intervals (CI) = 2.85-7.93 %) per 100 ticks.
      Maximum likelihood estimation of the infection rate varied by tick sex and
      developmental categories, ranging from 1.75 % (95 % CI = 0.11-8.11 %) in fed
      males to 6.81 % (95 % CI = 2.07-17.46 %) in unfed females. One amplicon from a
      fed adult female was 99 % identical to the sequence for Hepatozoon felis. The
      remaining sequences isolated from both dogs and ticks shared 99-100 % similarity
      with the corresponding H. canis isolates. This is the first detection of H. canis
      and H. felis in the tick R. sanguineus in Turkey.

PMID- 23535888
TI  - Efficient capture of pathogens with a zeolite matrix.
AB  - We show that a peptide linker sequence expressed as part of a fusion with protein
      G from Streptococcus binds to natural zeolite giving a complex to which a
      suitable antibody shows affinity binding. As a consequence, addition of the
      CRY104 antibody specific for an external surface epitope of Cryptosporidium
      allows the capture of this protozoan pathogen at high efficiency with the
      advantage of rapid concentration from water samples. The natural zeolite with the
      specific antibody attached was incorporated into a single and double zeolite
      column system. The results reported here show that it is possible to capture
      Cryptosporidium oocysts with outstanding efficiency (>90 %) from water and water
      incorporating QC-MUD using a size-sorted natural zeolite. The natural zeolite
      matrix not only allows for high flow rates but also for flexibility of column
      design and volume of water for sample collection. The system is versatile and it
      is possible to prepare columns with more than one specific surface antibody to
      allow the capture of one or two pathogens simultaneously.

PMID- 23535889
TI  - Detection of Leishmania infantum and identification of blood meals in Phlebotomus
      perniciosus from a focus of human leishmaniasis in Madrid, Spain.
AB  - Since 2010, the number of cases of both human visceral leishmaniasis and
      cutaneous leishmaniasis in southwestern Madrid region (Spain) and more
      specifically in the town of Fuenlabrada has increased. Direct xenodiagnosis of
      leishmaniasis proved that hares (Lepus granatensis) from this focus are able to
      infect with Leishmania infantum colonized Phlebotomus perniciosus. To a better
      understanding of this focus of leishmaniasis, we conducted an entomological
      survey using CDC light traps, at the end of the seasonal transmission period of
      2011 before the beginning of control measures of the disease, to study the
      phlebotomine sand flies species involved. Detection of Leishmania DNA in the sand
      flies captured was studied by kDNA-PCR and cpb-PCR. In addition, blood fed and
      gravid female P. perniciosus were analysed by a PCR based in vertebrate
      cytochrome b (cyt b) gene. Taxonomic identification of captured sand flies (n =
      174) as P. perniciosus (n = 171) and Sergentomyia minuta (n = 3) together with
      the analysis of blood feeding in ten sand flies that shows a high preference for
      hares (n = 6), followed by humans (n = 3), and cats (n = 1) confirm a strong
      association between P. perniciosus hares and humans in the focus. Moreover, 79
      out of 135 (58.5 %) P. perniciosus were positive to L. infantum by PCR
      approaches. These data support the increase of human leishmaniasis cases in the
      area and the existence of an unusual sylvatic cycle alternative to the classical
      domestic one, where the dog is the main reservoir of L. infantum.

PMID- 23535890
TI  - Electrochemical grafting of long spacer arms of hexamethyldiamine on a screen
      printed carbon electrode surface: application in target induced ochratoxin A
      electrochemical aptasensor.
AB  - A novel strategy based on direct electrochemistry of amino group on screen
      printed carbon electrode surface (SPCE) was purposed. The purposed method was
      employed for the label free detection of ochratoxin A (OTA). A long spacer arm of
      hexamethyldiamine was immobilized on SPCE via electrochemical oxidation of its
      terminal amino-group. The activated carboxy-aptamer was covalently linked to
      other amino terminal group of immobilized hexamethyldiamine. The designed
      immobilized macromolecules resulted in the formation of long clusters on SPCE
      surface, while aptamer acted as gate to block the entrance of these clusters. The
      aptamer gates were closed due to change in conformation of aptamer upon target
      analyte binding, decreasing the electrochemical signal. The decrease in
      electrochemical signal was used for the detection of target molecule.

PMID- 23535891
TI  - A novel fractionation approach for water constituents - distribution of storm
      event metals.
AB  - A novel fractionation method, based on both particle size and settling
      characteristics, was employed to examine metal distributions among five
      fractions. In-stream and stormwater runoff samples were collected from four land
      use types: highway, urban, agricultural (storm event and irrigation), and
      natural. Highway samples contained the highest dissolved concentrations for most
      metals, and freshwater ambient water quality criteria were exceeded for Cd, Cu,
      Pb, and Zn in the first storm of the water year. Anthropogenic sources were
      indicated for Cu, Zn, Cd, and Pb in highway and urban samples, and total metal
      loadings (mg km(-2)) were observed to be as follows: highway > urban >
      agricultural storm event ~ natural > agricultural irrigation. Notably, ~10-fold
      higher suspended solids concentration was observed in the agricultural storm
      event sample, and suspended solids-associated metals were correspondingly
      elevated. Distribution coefficients revealed the following affinities: Zn, Ni,
      Cd, and Pb to large dense particles; and Cu, Zn, Cr, Ni, and Pb to colloidal
      organic matter.

PMID- 23535893
TI  - Levonantradol: asymmetric synthesis and structural analysis.
AB  - The first asymmetric synthesis of a synthetic cannabinoid levonantradol was
      accomplished, and the 3-D solution structure of its core architecture was
      confirmed by NMR and computational methods.

PMID- 23535892
TI  - Temperature imaging of laser-induced thermotherapy (LITT) by MRI: evaluation of
      different sequences in phantom.
AB  - The purpose of this study was to evaluate magnetic resonance (MR) temperature
      imaging of the laser-induced thermotherapy (LITT) comparing the proton resonance
      frequency (PRF) and T 1 thermometry methods. LITT was applied to a liver
      mimicking acrylamide gel phantom. Temperature rise up to 70  degrees C was
      measured using a MR-compatible fiber-optic thermometer. MR imaging was performed
      by a 1.5-T scanner utilizing fast gradient echo sequences including a segmented
      echo planar imaging (seg-EPI) sequence for PRF and the following sequences for T
      1 method: fast low-angle shot (FLASH), inversion recovery turbo flash (IRTF),
      saturation recovery turbo flash (SRTF), and true fast imaging (TRUFI).
      Temperature-induced change of the pixel values in circular regions of interest,
      selected on images under the temperature probe tip, was recorded. For each
      sequence, a calibration constant could be determined to be -0.0088 +/- 0.0002 ppm
      degrees C(-1) (EPI), -1.15 +/- 0.03  degrees C(-1) (FLASH), -1.49 +/- 0.03 
      degrees C(-1) (IRTF), -1.21 +/- 0.03  degrees C(-1) (SRTF), and -2.52 +/- 0.12 
      degrees C(-1) (TRUFI). These constants were evaluated in further LITT experiments
      in phantom comparing the calculated temperatures with the fiber optic-measured
      ones; temperature precisions of 0.60  degrees C (EPI), 0.81  degrees C (FLASH),
      1.85  degrees C (IRTF), 1.95  degrees C (SRTF), and 3.36  degrees C (TRUFI) were
      obtained. Furthermore, performing the Bland-Altman analysis, temperature accuracy
      was determined to be 0.23  degrees C (EPI), 0.31  degrees C (FLASH), 1.66 
      degrees C (IRTF), 1.19  degrees C (SRTF), and 3.20  degrees C (TRUFI). In
      conclusion, the seg-EPI sequence was found to be more convenient for MR
      temperature imaging of LITT due to its relatively high precision and accuracy.
      Among the T 1 method sequences, FLASH showed the highest accuracy and robustness.

PMID- 23535894
TI  - Crystal structure of human Karyopherin beta2 bound to the PY-NLS of Saccharomyces
      cerevisiae Nab2.
AB  - Import-Karyopherin or Importin proteins bind nuclear localization signals (NLSs)
      to mediate the import of proteins into the cell nucleus. Karyopherin beta2 or
      Kapbeta2, also known as Transportin, is a member of this transporter family
      responsible for the import of numerous RNA binding proteins. Kapbeta2 recognizes
      a targeting signal termed the PY-NLS that lies within its cargos to target them
      through the nuclear pore complex. The recognition of PY-NLS by Kapbeta2 is
      conserved throughout eukaryotes. Kap104, the Kapbeta2 homolog in Saccharomyces
      cerevisiae, recognizes PY-NLSs in cargos Nab2, Hrp1, and Tfg2. We have determined
      the crystal structure of Kapbeta2 bound to the PY-NLS of the mRNA processing
      protein Nab2 at 3.05-A resolution. A seven-residue segment of the PY-NLS of Nab2
      is observed to bind Kapbeta2 in an extended conformation and occupies the same PY
      NLS binding site observed in other Kapbeta2.PY-NLS structures.

PMID- 23535895
TI  - [Use of 2 % hyperbaric prilocaine for spinal anesthesia : sensitivity analysis in
      outpatient surgery].
AB  - BACKGROUND: Hyperbaric prilocaine 2 % has been available for spinal anesthesia in
      Germany for 2 years and is characterized by a short duration of action, a lack of
      postspinal urine retention and a reduction of transient neurological syndromes.
      However, desirable pharmacological properties are contrasted by higher
      pharmacological costs compared to hyperbaric bupivacaine 0.5 %. MATERIALS AND
      METHODS: This paper deals with a sensitivity analysis for the use of hyperbaric
      prilocaine 2 % versus hyperbaric bupivacaine 0.5 % in Germany and investigates
      the financial break-even point up to which time a shorter patient stay in the
      recovery area compensates for the higher costs for the use of prilocaine 2 % for
      ambulatory spinal aaesthesia. A sensitivity analysis is an instrument of
      investment appraisal. It is a model to reduce a complex system with numerous
      variables to a straightforward calculation by assuming a framework requirement
      and systematically changing only one or two variables. In this paper additional
      costs for spinal anesthesia have been neglected, only the time a nurse spends
      with the patient in the recovery area and the costs for each vial of drug have
      been taken into account. RESULTS: For the assumption of 75 min time until leaving
      the recovery area and being discharged after spinal anesthesia with hyperbaric
      prilocaine 2 % versus 150 min (recovery of motor competence) or 405 min (voiding)
      with hyperbaric bupivacaine 0.5 % the calculation shows a cost benefit for
      hyperbaric prilocaine 2 % of EUR 11.64 or EUR 64.76 compared to hyperbaric
      bupivacaine 0.5 % and EUR 13.32 or EUR 66.44 compared to isobaric bupivacaine 0.5
      %. Under the assumption that all patients who have received spinal anesthesia
      with hyperbaric bupivacaine 0.5 % can be discharged from the recovery area after
      150 min, the use of hyperbaric prilocaine 2 % remains more economical as long as
      the patient is discharged from the recovery area within 130 min. If 405 min
      recovery time is assumed for hyperbaric bupivacaine 0.5 % the costs compared with
      hyperbaric prilocaine 2 % will be compensated after 300 min. To be more
      economical compared to patients with hyperbaric prilocaine 2 % those who received
      hyperbaric bupivacaine 0.5 % must be discharged from the recovery area within at
      least 100 min. However, a time of less than 160 min for discharge from the
      recovery area is not published anywhere in the literature. In summary, the use of
      hyperbaric prilocaine 2 % for 60 min operation time is cheaper than the use of
      bupivacaine 0.5 % as long as patients do not stay in the recovery area for longer
      than 120 min and are discharged from the recovery area. CONCLUSIONS: For German
      framework conditions the use of hyperbaric prilocaine 2 % can provide an
      economical advantage compared to the use of hyperbaric bupivacaine 0.5 % if staff
      assignment can be flexible.

PMID- 23535896
TI  - CD8(+) T cell activation by murine erythroblasts infected with malaria parasites.
AB  - Recent studies show that some human malaria parasite species Plasmodium
      falciparum and P. vivax parasitize erythroblasts; however, the biological and
      clinical significance of this is unclear. To investigate further, we generated a
      rodent malaria parasite (P. yoelii 17XNL) expressing GFP-ovalbumin (OVA). Its
      infectivity to erythroblasts was confirmed, and parasitized erythroblasts were
      capable of initiating malaria infections. Experiments showed that MHC class I
      molecules were highly expressed on parasitized erythroblasts. As CD8(+) T cells
      recognize MHC class I and peptide complexes on target cells, and are involved in
      protection or pathology against malaria, we examined whether erythroblasts are
      targeted by CD8(+) T cells. Purified non-parasitized erythroblasts pulsed with
      OVA peptides were recognized by OVA-specific CD8(+) T cells. Crucially,
      parasitized erythroblasts isolated from GFP-OVA-, but not GFP- infected-mice,
      activated OT-I CD8(+) T cells, indicating that CD8(+) T cells recognize
      parasitized erythroblasts in an antigen-specific manner.

PMID- 23535897
TI  - Efficient transduction of vascular smooth muscle cells with a translational
      AAV2.5 vector: a new perspective for in-stent restenosis gene therapy.
AB  - Coronary artery disease represents the leading cause of mortality in the
      developed world. Percutaneous coronary intervention involving stent placement
      remains disadvantaged by restenosis or thrombosis. Vascular gene therapy-based
      methods may be approached, but lack a vascular gene delivery vector. We report a
      safe and efficient long-term transduction of rat carotid vessels after balloon
      injury intervention with a translational optimized AAV2.5 vector. Compared with
      other known adeno-associated virus (AAV) serotypes, AAV2.5 demonstrated the
      highest transduction efficiency of human coronary artery vascular smooth muscle
      cells (VSMCs) in vitro. Local delivery of AAV2.5-driven transgenes in injured
      carotid arteries resulted in transduction as soon as day 2 after surgery and
      persisted for at least 30 days. In contrast to adenovirus 5 vector, inflammation
      was not detected in AAV2.5-transduced vessels. The functional effects of AAV2.5
      mediated gene transfer on neointimal thickening were assessed using the
      sarco/endoplasmic reticulum Ca(2+) ATPase isoform 2a (SERCA2a) human gene, known
      to inhibit VSMC proliferation. At 30 days, human SERCA2a messenger RNA was
      detected in transduced arteries. Morphometric analysis revealed a significant
      decrease in neointimal hyperplasia in AAV2.5-SERCA2a-transduced arteries: 28.36+/
      11.30 (n=8) vs 77.96+/-24.60 (n=10) MUm(2), in AAV2.5-green fluorescent protein
      infected, P<0.05. In conclusion, AAV2.5 vector can be considered as a promising
      safe and effective vector for vascular gene therapy.

PMID- 23535898
TI  - Adeno-associated virus serotype 9 efficiently targets ischemic skeletal muscle
      following systemic delivery.
AB  - Targeting therapeutic gene expression to the skeletal muscle following
      intravenous (IV) administration is an attractive strategy for treating peripheral
      arterial disease (PAD), except that vector access to the ischemic limb could be a
      limiting factor. As adeno-associated virus serotype 9 (AAV-9) transduces skeletal
      muscle at high efficiency following systemic delivery, we employed AAV-9 vectors
      bearing luciferase or enhanced green fluorescent protein (eGFP) reporter genes to
      test the hypothesis that increased desialylation of cell-surface glycans
      secondary to hindlimb ischemia (HLI) might help offset the reduction in tissue
      perfusion that occurs in mouse models of PAD. The utility of the creatine kinase
      based (CK6) promoter for restricting gene expression to the skeletal muscle was
      also examined by comparing it with the cytomegalovirus (CMV) promoter after
      systemic administration following surgically induced HLI. Despite reduced blood
      flow to the ischemic limbs, CK6 promoter-driven luciferase activities in the
      ischemic gastrocnemius (GA) muscles were ~34-, ~28- and ~150-fold higher than in
      the fully perfused contralateral GA, heart and liver, respectively, 10 days after
      IV administration. Furthermore, luciferase activity from the CK6 promoter in the
      ischemic GA muscles was ~twofold higher than with CMV, while in the liver CK6
      driven activity was ~42-fold lower than with CMV, demonstrating that the
      specificity of ischemic skeletal muscle transduction can be further improved with
      the muscle-specific promoters. Studies with Evans blue dye and fluorescently
      labeled lectins revealed that vascular permeability and desialylation of the cell
      surface glycans were increased in the ischemic hindlimbs. Furthermore,
      AAV9/CK6/Luc vector genome copy numbers were ~sixfold higher in the ischemic
      muscle compared with the non-ischemic muscle in the HLI model, whereas this trend
      was reversed when the same genome was packaged in the AAV-1 capsid (which binds
      sialylated, as opposed to desialylated glycans), further underscoring the
      importance of desialylation in the ischemic enhancement of transduction displayed
      by AAV-9. Taken together, these findings suggest two complementary mechanisms
      contributing to the preferential transduction of ischemic muscle by AAV-9:
      increased vascular permeability and desialylation. In conclusion, ischemic muscle
      is preferentially targeted following systemic administration of AAV-9 in a mouse
      model of HLI. Unmasking of the primary AAV-9 receptor as a result of ischemia may
      contribute importantly to this effect.

PMID- 23535899
TI  - Disease correction by combined neonatal intracranial AAV and systemic lentiviral
      gene therapy in Sanfilippo Syndrome type B mice.
AB  - Mucopolysaccharidosis type IIIB (MPS IIIB) or Sanfilippo Syndrome type B is a
      lysosomal storage disease resulting from the deficiency of N-acetyl
      glucosaminidase (NAGLU) activity. We previously showed that intracranial adeno
      associated virus (AAV)-based gene therapy results in partial improvements of
      several aspects of the disease. In an attempt to further correct the disease, MPS
      IIIB mice were treated at 2-4 days of age with intracranial AAV2/5-NAGLU (IC
      AAV), intravenous lentiviral-NAGLU (IV-LENTI) or the combination of both (BOTH).
      The BOTH group had the most complete biochemical and histological improvements of
      any treatment group. Compared with untreated MPS IIIB animals, all treatments
      resulted in significant improvements in motor function (rotarod) and hearing
      (auditory-evoked brainstem response). In addition, each treatment group had a
      significantly increased median life span compared with the untreated group (322
      days). The combination arm had the greatest increase (612 days), followed by IC
      AAV (463 days) and IV-LENTI (358 days). Finally, the BOTH group had nearly normal
      circadian rhythm measures with improvement in time to activity onset. In summary,
      targeting both the systemic and central nervous system disease of MPS IIIB early
      in life appears to be the most efficacious approach for this inherited metabolic
      disorder.

PMID- 23535900
TI  - Cognitive disorders and occupational exposure to organophosphates: results from
      the PHYTONER study.
AB  - The involvement of organophosphate insecticides in cognitive disorders is
      supported by epidemiologic and biological evidence, but the effects of long-term
      exposure remain debated. We studied the association between organophosphate
      exposure and cognitive performance in vine workers from the PHYTONER study cohort
      in the Bordeaux area of France. Results from interviews of 614 subjects conducted
      at the 4-year follow-up between 2001 and 2003 were analyzed. Exposure to
      pesticides since 1950 was assessed with cumulative exposure scores for 34
      organophosphates combining an historical crop-exposure pesticide matrix and field
      exposure studies, taking into account the characteristics of treatment (mixing,
      spraying, equipment cleaning) and reentry tasks. For the 11 organophosphates
      retained in the analysis, exposure (ever vs. never) was associated with low
      cognitive performance. No dose-effect relationship was found, but an increased
      risk was observed with a 50-mg increase in the cumulative score, which was
      greater with mevinphos (Benton Visual Retention Test: odds ratio = 3.26, 95%
      confidence interval: 1.54, 6.88; Trail Making Test, part A: odds ratio = 3.03,
      95% confidence interval: 1.39, 6.62). Our results support the hypothesis that
      cognitive disorders observed in vine workers may be associated with exposure to
      specific organophosphates.

PMID- 23535901
TI  - Serum phospholipid fatty acids, genetic variation in myeloperoxidase, and
      prostate cancer risk in heavy smokers: a gene-nutrient interaction in the
      carotene and retinol efficacy trial.
AB  - The authors investigated associations of serum phospholipid n-3 and n-6
      polyunsaturated fatty acids (PUFAs) and trans-fatty acids with prostate cancer
      risk, and whether myeloperoxidase G-463A (rs2333227) modified the associations in
      the Carotene and Retinol Efficacy Trial (CARET) (Seattle, Washington; Irvine,
      California; New Haven, Connecticut; San Francisco, California; Baltimore,
      Maryland; and Portland, Oregon, 1985-2003). Prerandomization sera were assayed
      for fatty acids among 641 men with incident prostate cancer (368 nonaggressive
      and 273 aggressive (stage III/IV or Gleason score >=7)) and 1,398 controls.
      Overall, dihomo-gamma-linolenic (quartiles 4 vs. 1: odds ratio (OR) = 0.66, 95%
      confidence interval (CI): 0.49, 0.95; P(trend) = 0.024) and docosatetraenoic (OR
      = 0.69, 95% CI: 0.46, 1.02; P(trend) = 0.011) acids were inversely associated
      with nonaggressive and aggressive prostate cancer risks, respectively. Among men
      with MPO GG, the genotype upregulating oxidative stress, quartiles 4 versus 1
      eicosapentaenoic plus docosahexaenoic acids were suggestively associated with an
      increased risk of aggressive prostate cancer (OR = 1.66, 95% CI: 0.95, 2.92;
      P(trend) = 0.07). However, the association was the inverse among men with MPO
      GA/AA genotypes (P(interaction) = 0.011). Interactions were also observed for
      docosapentaenoic acid, total n-3 PUFAs, and arachidonic acid. MPO GA/AA vs. GG
      was associated with a 2-fold increase in aggressive prostate cancer risk among
      men with low (quartile 1) n-3 PUFAs. This study adds important evidence linking
      oxidative stress with prostate carcinogenesis.

PMID- 23535902
TI  - Catch-up growth in Japanese quail (Coturnix Japonica): relationships with food
      intake, metabolic rate and sex.
AB  - The effects of early environmental conditions can profoundly affect individual
      development and adult phenotype. In birds, limiting resources can affect growth
      as nestlings, but also fitness and survival as adults. Following periods of food
      restriction, individuals may accelerate development, undergoing a period of rapid
      "catch-up" growth, in an attempt to reach the appropriate size at adulthood.
      Previous studies of altricial birds have shown that catch-up growth can have
      negative consequences in adulthood, although this has not been explored in
      species with different developmental strategies. Here, we investigated the
      effects of resource limitation and the subsequent period of catch-up growth, on
      the morphological and metabolic phenotype of adult Japanese quail (Coturnix
      japonica), a species with a precocial developmental strategy. Because males and
      females differ in adult body size, we also test whether food restriction had sex
      specific effects. Birds that underwent food restriction early in development had
      muscles of similar size and functional maturity, but lower adult body mass than
      controls. There was no evidence of sex-specific sensitivity of food restriction
      on adult body mass; however, there was evidence for body size. Females fed ad lib
      were larger than males fed ad lib, while females subjected to food restriction
      were of similar size to males. Adults that had previously experienced food
      restriction did not have an elevated metabolic rate, suggesting that in contrast
      to altricial nestlings, there was no metabolic carry-over effect of catch-up
      growth into adulthood. While Japanese quail can undergo accelerated growth after
      re-feeding, timing of food restriction may be important to adult size,
      particularly in females. However, greater developmental flexibility compared to
      altricial birds may contribute to the lack of metabolic carryover effects at
      adulthood. 

PMID- 23535904
TI  - Pulse HIV vaccination: feasibility for virus eradication and optimal vaccination
      schedule.
AB  - We modify the classical virus dynamics model by incorporating an immune response
      with fixed or fluctuating vaccination frequencies and dosages to obtain a system
      of impulsive differential equations for the virus dynamics of both the wild-type
      and mutant strains. This model framework permits us to obtain precise conditions
      for the virus elimination, which are much more feasible compared with existing
      results, which require frequent vaccine administration with large dosage. We also
      consider the corresponding impulsive optimal control problem to describe when and
      how much of the vaccine should be administered in order to maximize levels of
      healthy CD4(+) T cells and immune response cells. A gradient-based optimization
      method is applied to obtain the optimal schedule numerically. For a case study
      when the CTL vaccine is administered in a period of one year, our numerical
      studies support the optimal vaccination schedule consisting of vaccine
      administration three times, with the first dosage strong (to boost the immune
      system), followed by a second dosage shortly after (to strengthen the immune
      response) and then the third and final dosage long after (to ensure the immune
      system can handle viruses rebound).

PMID- 23535905
TI  - Modelling the use of Wolbachia to control dengue fever transmission.
AB  - Experiments and field trials have shown that the intracellular bacterium
      Wolbachia may be introduced into populations of the mosquito Aedes aegypti, the
      primary vector for dengue fever. In the absence of Wolbachia, a mosquito
      acquiring the dengue virus from an infected human enters an exposed (infected but
      not infectious) period before becoming infectious itself. A Wolbachia-infected
      mosquito that acquires dengue (i) may have a reduced lifespan, so that it is less
      likely to survive the exposed period and become infectious, and (ii) may have a
      reduced ability to transmit dengue, even if it has survived the exposed period.
      Wolbachia introduction has therefore been suggested as a potential dengue control
      measure. We set up a mathematical model for the system to investigate this
      suggestion and to evaluate the desirable properties of the Wolbachia strain to be
      introduced. We show that Wolbachia has excellent potential for dengue control in
      areas where R 0 is not too large. However, if R 0 is large, Wolbachia strains
      that reduce but do not eliminate dengue transmission have little effect on
      endemic steady states or epidemic sizes. Unless control measures to reduce R 0 by
      reducing mosquito populations are also put in place, it may be worth the extra
      effort in such cases to introduce Wolbachia strains that eliminate dengue
      transmission completely.

PMID- 23535903
TI  - Canonical Wnt/beta-catenin signaling drives human schwann cell transformation,
      progression, and tumor maintenance.
AB  - Genetic changes required for the formation and progression of human Schwann cell
      tumors remain elusive. Using a Sleeping Beauty forward genetic screen, we
      identified several genes involved in canonical Wnt signaling as potential drivers
      of benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). In
      human neurofibromas and MPNSTs, activation of Wnt signaling increased with tumor
      grade and was associated with downregulation of beta-catenin destruction complex
      members or overexpression of a ligand that potentiates Wnt signaling, R-spondin 2
      (RSPO2). Induction of Wnt signaling was sufficient to induce transformed
      properties in immortalized human Schwann cells, and downregulation of this
      pathway was sufficient to reduce the tumorigenic phenotype of human MPNST cell
      lines. Small-molecule inhibition of Wnt signaling effectively reduced the
      viability of MPNST cell lines and synergistically induced apoptosis when combined
      with an mTOR inhibitor, RAD-001, suggesting that Wnt inhibition represents a
      novel target for therapeutic intervention in Schwann cell tumors.

PMID- 23535907
TI  - Synthesis and photovoltaic properties of acceptor materials based on the
      dimerization of fullerene C60 for use in efficient polymer solar cells.
AB  - We demonstrate that dimeric fullerene derivatives work as an excellent n-type
      material for polymer solar cells in combination with P3HT or PTB7, showing the
      best PCE of 3.3% or 6.1%, respectively. The device performance was influenced by
      the position of the two C60 moieties linked together.

PMID- 23535906
TI  - A dinucleating ligand which promotes DNA cleavage with one and without a
      transition metal ion.
AB  - The dinucleating ligand L (1,3-bis[bis(pyridin-2-ylmethyl)amino]propan-2-ol)
      combined with metal ions efficiently cleaves DNA when M : L is 1 : 1 (M = Co(II)
      or Fe(III)) at pH 5.5-7.0, with free L being more active at acidic pH than when
      bound to Zn(II), Cu(II) or Ni(II) at neutral pH.

PMID- 23535908
TI  - Alteration of IGFBP-1 in soccer players due to intensive training.
AB  - Physical activity is accompanied by the changes in Insulin-like Growth Factor I
      (IGF-I)/IGF-Binding Protein 1 (IGFBP-1) axis. Inconsistent results concerning IGF
      I and IGFBP-1 levels were reported. In this study we have raised some questions
      on the events that occur at the molecular level of the exercise-related IGFBP-1
      changes. We have examined the fragmentation pattern of IGFBP-1, IGFBP-1 protease
      activity, interaction between IGFBP-1 and alpha2-macroglobulin (alpha2M), and
      possible existence of minor structural changes of IGFBP-1 in professional soccer
      players. Athletes had significantly greater amounts of fragmented IGFBP-1,
      whereas no difference was found in the amount of intact IGFBP-1 compared with
      controls. An increased activity of matrix metalloprotease-9 (MMP-9) was detected
      in athletes, causing IGFBP-1 degradation down to the fragment of 9 kDa as the
      major one. The amount of alpha2M, which protects IGFBP-1 from proteolysis, or the
      amount of IGFBP-1/alpha2M complexes was unaltered. Finally, we have examined
      whether IGFBP-1 isolated from soccer players exhibited altered reactivity with
      several chemical surfaces used in surface-enhanced laser desorption/ionization
      time of flight mass spectrometry (SELDI-TOF MS). Different reactivity was
      detected with anion and cation exchangers, suggesting existence of at least one
      sequence within IGFBP-1, whose ionization pattern was not equal in athletes and
      controls. Differences in spectra obtained with ion exchanges may reflect
      differences in IGFBP-1 phosphorylation. Physiological implications of the events
      described in this study on the IGF-I availability are, at this time, unknown. It
      can be hypothesized that IGFBP-1 proteolysis leads to altered distribution of IGF
      I among IGFBPs, which may affect the final IGF-associated response. 

PMID- 23535909
TI  - A new family of bioorthogonally applicable fluorogenic labels.
AB  - Synthetic procedures for the construction of fluorogenic azido-labels were
      developed. Photophysical properties were elaborated by experimental and
      theoretical investigations. Of the newly synthesized fluorogenic and
      bioorthogonally applicable dyes two were selected on the basis of their
      fluorogenic performance and further subjected to in vitro and in vivo studies.
      Both tags exhibited excellent fluorogenic properties as in aqueous medium, the
      azide form of the selected dyes is virtually non-fluorescent, while their
      "clicked" triazole congeners showed intense fluorescence. One of these labels
      showed a very large Stokes shift. To the best of our knowledge this is the first
      reported case of mega-Stokes type of fluorogenic labels. These studies have
      justified that these two fluorogenic tags are remarkably suitable for
      bioorthogonal tagging schemes. The developed synthetic approach together with the
      theoretical screen of possible fluorogenic tags will enable the generation of
      libraries of such tags in the future.

PMID- 23535910
TI  - Experimental and theoretical studies on the coordination chemistry of the N1
      hexyl substituted pyrimidines (uracil, 5-fluorouracil and cytosine).
AB  - N(1)-Hexyl substituted pyrimidines were shown to present solubility properties
      closer to the real bases than the commonly used methyl and ethyl derivatives,
      yielding bi-layered structures in the solid state. The study of their
      coordination capabilities, mainly with Ag(I) and Hg(II), is presented in order to
      prove their reactivity. A series of coordination complexes, namely, [Hg(N(1)
      hexyl-5-fluorouracilate)2]4.6H2O (1), (Ag(+)).[Ag(N(1)-hexyl-5
      fluorouracilate)2](-) (2), [Ag(NO3)(N(1)-hexyluracil-kappaO(4))4] (3),
      [ZnBr2(N(1)-hexylcytosine)2] (4), [CdBr2(N(1)-hexylcytosine)2] (5), [HgBr2(N(1)
      hexylcytosine)2] (6) and [CoBr2(N(1)-hexylcytosine)2] (7), have been synthesized
      in good yields and X-ray characterized. The presence of the hexyl chains and the
      fluorine atoms causes the formation of interesting 3D architectures in the solid
      state. Their structures have been further characterized by infrared spectra (IR)
      and elemental analyses. In addition, DFT-D3 calculations are used to study
      interesting noncovalent interactions observed in the solid state, like fluorine
      fluorine, fluorine-pi and hydrophobic interactions.

PMID- 23535912
TI  - Graphene oxide embedded sandwich nanostructures for enhanced Raman readout and
      their applications in pesticide monitoring.
AB  - Analytical techniques based on surface-enhanced Raman scattering (SERS) suffer
      from a lack of reproducibility and reliability, thus hampering their practical
      applications. Herein, we have developed a SERS-active substrate based on a
      graphene oxide embedded sandwich nanostructure for ultrasensitive Raman signal
      readout. By using this novel Au@Ag NPs/GO/Au@Ag NPs sandwich nanostructure as a
      SERS substrate, the Raman signals of analytes were dramatically enhanced due to
      having plenty of hot spots on their surfaces and the unique structure of the
      graphene oxide sheets. These features make the sandwich nanostructured film an
      ideal SERS substrate to improve the sensitivity, reproducibility and reliability
      of the Raman readout. The sandwich nanostructure film can be applied to detect
      rhodamine-6G (R6G) with an enhancement factor (EF) of ~7.0 * 10(7) and the
      pesticide thiram in commercial grape juice with a detection limit of as low as
      0.1 MUM (0.03 ppm), which is much lower than the maximal residue limit (MRL) of 7
      ppm in fruit prescribed by the U.S. Environmental Protection Agency (EPA). The GO
      embedded sandwich nanostructure also has the ability to selectively detect
      dithiocarbamate compounds over other types of agricultural chemical. Furthermore,
      spiked tests show that the sandwich nanostructure can be used to monitor thiram
      in natural lake water and commercial grape juice without further treatment. In
      addition, the GO enhanced Raman spectroscopic technique offers potential
      practical applications for the on-site monitoring and assessment of pesticide
      residues in agricultural products and environments.

PMID- 23535911
TI  - Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB
      genes are associated with development and progression of nonalcoholic fatty liver
      disease in Japan.
AB  - We examined the genetic background of nonalcoholic fatty liver disease (NAFLD) in
      the Japanese population, by performing a genome-wide association study (GWAS).
      For GWAS, 392 Japanese NAFLD subjects and 934 control individuals were analyzed.
      For replication studies, 172 NAFLD and 1,012 control subjects were monitored.
      After quality control, 261,540 single-nucleotide polymorphisms (SNPs) in
      autosomal chromosomes were analyzed using a trend test. Association analysis was
      also performed using multiple logistic regression analysis using genotypes, age,
      gender and body mass index (BMI) as independent variables. Multiple linear
      regression analyses were performed to evaluate allelic effect of significant SNPs
      on biochemical traits and histological parameters adjusted by age, gender, and
      BMI. Rs738409 in the PNPLA3 gene was most strongly associated with NAFLD after
      adjustment (P = 6.8 * 10(-14), OR = 2.05). Rs2896019, and rs381062 in the PNPLA3
      gene, rs738491, rs3761472, and rs2143571 in the SAMM50 gene, rs6006473,
      rs5764455, and rs6006611 in the PARVB gene had also significant P values (<2.0 *
      10(-10)) and high odds ratios (1.84-2.02). These SNPs were found to be in the
      same linkage disequilibrium block and were associated with decreased serum
      triglycerides and increased aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) in NAFLD patients. These SNPs were associated with
      steatosis grade and NAFLD activity score (NAS). Rs738409, rs2896019, rs738491,
      rs6006473, rs5764455, and rs6006611 were associated with fibrosis. Polymorphisms
      in the SAMM50 and PARVB genes in addition to those in the PNPLA3 gene were
      observed to be associated with the development and progression of NAFLD.

PMID- 23535914
TI  - A method for DNA-based detection of E. coli O157:H7 in a proteinous background
      using piezoelectric-excited cantilever sensors.
AB  - We show for the first time the detection of ~700 E. coli O157:H7 (EC) in both
      buffer and proteinous sample (beef wash) using the virulent gene stx2 as a
      sensing molecule immobilized on piezoelectric-excited millimeter cantilever
      (PEMC) sensors without a sample preparation step. Genomic DNA of EC suspended in
      buffer or beef wash was extracted using a 30-minute procedure, or using a
      commercial extraction kit, and then was exposed to the sensor immobilized with a
      19-mer probe that is complement to stx2 gene. As hybridization occurred, the
      resonant frequency of the cantilever sensor decreased due to the increased
      attached mass indicating the presence of stx2 gene in the sample. Wild strain
      JM101 subjected to the same preparation and procedure did not induce a
      hybridization response, nor did the genomic extract of EC with a bare sensor.
      PEMC sensor responses to diluted genomic extracts indicate that a much lower
      concentration of 700 cells is detectable. In order to compare the results with
      antibody-based detection, samples with EC at 2500 cells per mL were exposed to
      antibody-immobilized PEMC sensors which gave reproducible responses confirming
      previous experiments with such samples.

PMID- 23535915
TI  - Comparing the sensitivity of geographically distinct Lemna minor populations to
      atrazine.
AB  - The objectives of this study were to compare the sensitivities of field
      populations and a laboratory culture of a duckweed species (Lemna minor) to the
      herbicide atrazine using three different endpoints and to determine whether
      sensitivity to atrazine was affected by past exposure to the herbicide. L. minor
      cultures were purchased commercially or collected from field sites within an
      agricultural watershed and exposed to atrazine for 7 days under greenhouse
      conditions. Populations differed significantly in their sensitivity to atrazine.
      Biomass was more sensitive than frond number, while chlorophyll fluorescence was
      not a sensitive endpoint. Overall, the sensitivity of the various populations to
      atrazine was not strongly related to measures of past exposure to agriculture
      stressors. Positive correlations between biomass twenty-five percent inhibition
      concentrations (IC25s), biomass estimated marginal means and in-stream atrazine
      concentrations were observed, providing evidence that atrazine exposure is linked
      to a decrease in sensitivity to atrazine. However, IC25s generated for each
      population were similar, ranging from 19 to 40 and 57 to 92 MUg/L atrazine for
      biomass and frond data respectively, and likely do not represent biologically
      significant differences in atrazine sensitivity. Given the small range in
      sensitivity observed between populations, commercial laboratory cultures appear
      to provide a good estimate of the sensitivity of field populations of L. minor to
      atrazine and should continue to be used in regulatory phytotoxicity testing.

PMID- 23535913
TI  - Targeted expression in zebrafish primordial germ cells by Cre/loxP and Gal4/UAS
      systems.
AB  - In zebrafish and other vertebrates, primordial germ cells (PGCs) are a population
      of embryonic cells that give rise to sperm and eggs in adults. Any type of
      genetically manipulated lines have to be originated from the germ cells of the
      manipulated founders, thus it is of great importance to establish an effective
      technology for highly specific PGC-targeted gene manipulation in vertebrates. In
      the present study, we used the Cre/loxP recombinase system and Gal4/UAS
      transcription system for induction and regulation of mRFP (monomer red
      fluorescent protein) gene expression to achieve highly efficient PGC-targeted
      gene expression in zebrafish. First, we established two transgenic activator
      lines, Tg(kop:cre) and Tg(kop:KalTA4), to express the Cre recombinases and the
      Gal4 activator proteins in PGCs. Second, we generated two transgenic effector
      lines, Tg(kop:loxP-SV40-loxP-mRFP) and Tg(UAS:mRFP), which intrinsically showed
      transcriptional silence of mRFP. When Tg(kop:cre) females were crossed with
      Tg(kop:loxP-SV40-loxP-mRFP) males, the loxP flanked SV40 transcriptional stop
      sequence was 100 % removed from the germ cells of the transgenic hybrids. This
      led to massive production of PGC-specific mRFP transgenic line, Tg(kop:loxP
      mRFP), from an mRFP silent transgenic line, Tg(kop:loxP-SV40-loxP-mRFP). When
      Tg(kop:KalTA4) females were crossed with Tg(UAS:mRFP) males, the hybrid embryos
      showed PGC specifically expressed mRFP from shield stage till 25 days post
      fertilization (pf), indicating the high sensitivity, high efficiency, and long
      lasting effect of the Gal4/UAS system. Real-time PCR analysis showed that the
      transcriptional amplification efficiency of the Gal4/UAS system in PGCs can be
      about 300 times higher than in 1-day-pf embryos. More importantly, when the
      UAS:mRFP-nos1 construct was directly injected into the Tg(kop:KalTA4) embryos, it
      was possible to specifically label the PGCs with high sensitivity, efficiency,
      and persistence. Therefore, we have established two targeted gene expression
      platforms in zebrafish PGCs, which allows us to further manipulate the PGCs of
      zebrafish at different levels.

PMID- 23535916
TI  - Characterizing the distribution and rates of microbial sulfate reduction at
      Middle Valley hydrothermal vents.
AB  - Few studies have directly measured sulfate reduction at hydrothermal vents, and
      relatively little is known about how environmental or ecological factors
      influence rates of sulfate reduction in vent environments. A better understanding
      of microbially mediated sulfate reduction in hydrothermal vent ecosystems may be
      achieved by integrating ecological and geochemical data with metabolic rate
      measurements. Here we present rates of microbially mediated sulfate reduction
      from three distinct hydrothermal vents in the Middle Valley vent field along the
      Juan de Fuca Ridge, as well as assessments of bacterial and archaeal diversity,
      estimates of total biomass and the abundance of functional genes related to
      sulfate reduction, and in situ geochemistry. Maximum rates of sulfate reduction
      occurred at 90  degrees C in all three deposits. Pyrosequencing and functional
      gene abundance data revealed differences in both biomass and community
      composition among sites, including differences in the abundance of known sulfate
      reducing bacteria. The abundance of sequences for Thermodesulfovibro-like
      organisms and higher sulfate reduction rates at elevated temperatures suggests
      that Thermodesulfovibro-like organisms may have a role in sulfate reduction in
      warmer environments. The rates of sulfate reduction presented here suggest that-
      within anaerobic niches of hydrothermal deposits--heterotrophic sulfate reduction
      may be quite common and might contribute substantially to secondary productivity,
      underscoring the potential role of this process in both sulfur and carbon cycling
      at vents.

PMID- 23535917
TI  - Biphasic assembly of the murine intestinal microbiota during early development.
AB  - The birth canal provides mammals with a primary maternal inoculum, which develops
      into distinctive body site-specific microbial communities post-natally. We
      characterized the distal gut microbiota from birth to weaning in mice. One-day
      old mice had colonic microbiota that resembled maternal vaginal communities, but
      at days 3 and 9 of age there was a substantial loss of intestinal bacterial
      diversity and dominance of Lactobacillus. By weaning (21 days), diverse
      intestinal bacteria had established, including strict anaerobes. Our results are
      consistent with vertical transmission of maternal microbiota and demonstrate a
      nonlinear ecological succession involving an early drop in bacterial diversity
      and shift in dominance from Streptococcus to Lactobacillus, followed by an
      increase in diversity of anaerobes, after the introduction of solid food.
      Mammalian newborns are born highly susceptible to colonization, and lactation may
      control microbiome assembly during early development.

PMID- 23535919
TI  - Hollow mesoporous ceria nanoreactors with enhanced activity and stability for
      catalytic application.
AB  - Novel hollow mesoporous @M/CeO(2) (M = Au, Pd, and Au-Pd) nanospheres are
      created. The nanospheres can be used as effective nanoreactors with superior
      catalytic activity and stability for reduction of 4-nitrophenol due to their
      hollow mesoporous structural features.

PMID- 23535921
TI  - Priorities for improving drug research, development and regulation.

PMID- 23535922
TI  - Antibody drugs set to revive flagging migraine target.

PMID- 23535918
TI  - Bacterial community structure on two alpine debris-covered glaciers and
      biogeography of Polaromonas phylotypes.
AB  - High-elevation cold environments are considered ideal places to test hypotheses
      about mechanisms of bacterial colonization and succession, and about bacterial
      biogeography. Debris-covered glaciers (glaciers whose ablation area is mainly
      covered by a continuous layer of rock debris fallen from the surrounding
      mountains) have never been investigated in this respect so far. We used the
      Illumina technology to analyse the V5 and V6 hypervariable regions of the
      bacterial 16S rRNA gene amplified from 38 samples collected in July and September
      2009 at different distances from the terminus on two debris-covered glaciers
      (Miage and Belvedere--Italian Alps). Heterotrophic taxa-dominated communities and
      bacterial community structure changed according to ice ablation rate, organic
      carbon content of the debris and distance from the glacier terminus. Bacterial
      communities therefore change during downwards debris transport, and organic
      carbon of these recently exposed substrates is probably provided more by
      allochthonous deposition of organic matter than by primary production by
      autotrophic organisms. We also investigated whether phylotypes of the genus
      Polaromonas, which is ubiquitous in cold environments, do present a
      biogeographical distribution by analysing the sequences retrieved in this study
      together with others available in the literature. We found that the genetic
      distance among phylotypes increased with geographic distance; however, more
      focused analyses using discrete distance classes revealed that both sequences
      collected at sites <100 km and at sites 9400-13,500 km to each other were more
      similar than those collected at other distance classes. Evidences of
      biogeographic distribution of Polaromonas phylotypes were therefore contrasting.

PMID- 23535923
TI  - Anticancer IGF1R classes take more knocks.

PMID- 23535926
TI  - Market watch: Upcoming market catalysts in Q2 2013.

PMID- 23535924
TI  - Molecular imaging as a de-risking tool: coming into focus?

PMID- 23535927
TI  - Deal watch: Chiasma and Roche partner in oral peptide drug delivery.

PMID- 23535929
TI  - Paul Stoffels. Interview by Asher Mullard.

PMID- 23535930
TI  - Antibody-drug conjugates.

PMID- 23535931
TI  - Radiation injury: EGF aids recovery after blast of radiation.

PMID- 23535932
TI  - Blood disorders: Epigenetically enhancing haemoglobin production.

PMID- 23535935
TI  - Myosin Mg-ATPase of molluscan muscles is slightly activated by F-actin under
      catch state in vitro.
AB  - Molluscan muscle twitchin, a titin/connectin-related giant protein, regulates
      interactions between actin and myosin filaments at low Ca(2+) concentrations.
      When it is dephosphorylated, actin filaments tightly bind to myosin filaments,
      resulting in the catch state known as the state of high passive tension with very
      low energy consumption. Yet when twitchin is phosphorylated actin filaments
      detach from the myosin filaments, resulting in relaxation of the catch. Here,
      steady-state Mg-ATPase activities of purified myosin were measured under various
      conditions: without twitchin, with dephosphorylated twitchin, or with
      phosphorylated twitchin; with or without phalloidin-stabilized F-actin; and at
      various Ca(2+) concentrations. At low Ca(2+) concentration, Mg-ATPase was
      activated by F-actin only in the presence of dephosphorylated twitchin (catch
      state). The activation was about two orders lower than that fully activated by
      Ca(2+) and F-actin. In the absence of F-actin, twitchin and its phosphorylation
      state did not affect Mg-ATPase activities in any of the conditions we tested.
      Based on these results, we propose a molecular mechanism for the catch, where
      twitchin alone does not interact with the myosin catalytic motor domain but its
      complex with F-actin does, forming the bridge between actin and myosin filaments
      and the myosin slowly hydrolyzes Mg-ATP in the catch state.

PMID- 23535936
TI  - Vitamin D status and supplementation in elite Irish athletes.
AB  - BACKGROUND: A high prevalence of vitamin D insufficiency/deficiency, which may
      impact on health and training ability, is evident among athletes worldwide. This
      observational study investigated the vitamin D status of elite Irish athletes and
      determined the effect of wintertime supplementation on status. METHODS: Serum 25
      hydroxyvitamin D [25(OH)D], calcium, and plasma parathyroid hormone were analyzed
      in elite athletes in November 2010 (17 boxers, 33 paralympians) or March 2011 (34
      Gaelic Athletic Association [GAA] players). A subset of boxers and paralympians
      (n = 27) were supplemented during the winter months with either 5,000 IU vitamin
      D3/d for 10-12 weeks or 50,000 IU on one or two occasions. Biochemical analysis
      was repeated following supplementation. RESULTS: Median 25(OH)D of all athletes
      at baseline was 48.4 nmol/L. Vitamin D insufficiency/deficiency (serum 25(OH)D
      <50 nmol/L) was particularly evident among GAA players (94%) due to month of
      sampling. Wintertime supplementation (all doses) significantly increased 25(OH)D
      (median 62.8 nmol/L at baseline vs. 71.1 nmol/L in April or May; p = .001) and
      corrected any insufficiencies/deficiencies in this subset of athletes. In
      contrast, 25(OH)D significantly decreased in those that did not receive a vitamin
      D supplement, with 74% of athletes classed as vitamin D insufficient/deficient
      after winter, compared with only 35% at baseline. CONCLUSIONS: This study has
      highlighted a high prevalence of vitamin D insufficiency/ deficiency among elite
      Irish athletes and demonstrated that wintertime vitamin D3 supplementation is an
      appropriate regimen to ensure vitamin D sufficiency in athletes during winter and
      early spring.

PMID- 23535937
TI  - Dynamic constitutional electrodes toward functional fullerene wires.
AB  - Constitutional mesoporous thin-layer electrodes have been used to generate
      confined fullerene wires allowing a capacitive diffusion of electrons.

PMID- 23535934
TI  - Challenges and approaches for the development of safer immunomodulatory
      biologics.
AB  - Immunomodulatory biologics, which render their therapeutic effects by modulating
      or harnessing immune responses, have proven their therapeutic utility in several
      complex conditions including cancer and autoimmune diseases. However, unwanted
      adverse reactions--including serious infections, malignancy, cytokine release
      syndrome, anaphylaxis and hypersensitivity as well as immunogenicity--pose a
      challenge to the development of new (and safer) immunomodulatory biologics. In
      this article, we assess the safety issues associated with immunomodulatory
      biologics and discuss the current approaches for predicting and mitigating
      adverse reactions associated with their use. We also outline how these approaches
      can inform the development of safer immunomodulatory biologics.

PMID- 23535938
TI  - Ligase chain reaction coupled with rolling circle amplification for high
      sensitivity detection of single nucleotide polymorphisms.
AB  - We present a highly sensitive and homogeneous assay for the detection of single
      nucleotide polymorphisms (SNPs) by ligase chain reaction (LCR) coupled with
      rolling circle amplification (RCA). The LCR probes include one pair of probes and
      a padlock probe (PLP). In the LCR, one pair of probes composed of X and Y,
      perfectly hybridize with the upper strand of the target DNA after thermal
      denaturation. They are then ligated by the thermostable ligase to form the
      ligation product of XY. At the same time, the PLP hybridizes with the lower
      strand of the target DNA and are ligated to form the circular PLP (cPLP). After
      repeated cycles of denaturation, annealing, and ligation, the target DNA is
      amplified exponentially to generate a large number of XY and cPLPs. Subsequently,
      RCA is triggered by the cPLP as a template and XY as a primer, producing large
      numbers of long strand DNA products, which are detected by binding with the
      fluorescent dye, SYBR Green I, in a homogeneous manner. This method is simple,
      and avoids the need for detection of the LCR products with labeled probes and
      complex separation steps. The assay is sensitive and specific enough to detect a
      1 fM target DNA molecule. It is possible to accurately determine the allele
      frequency as low as 1.0%. The LCR coupled with RCA assay extends the application
      of the LCR and RCA, and provides a new strategy for detecting SNPs as well as
      nucleic acid analysis, immunoassay, and molecular diagnosis.

PMID- 23535933
TI  - Adenosine receptors as drug targets--what are the challenges?
AB  - Adenosine signalling has long been a target for drug development, with adenosine
      itself or its derivatives being used clinically since the 1940s. In addition,
      methylxanthines such as caffeine have profound biological effects as antagonists
      at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act
      by enhancing the activation of adenosine receptors. There is strong evidence that
      adenosine has a functional role in many diseases, and several pharmacological
      compounds specifically targeting individual adenosine receptors--either directly
      or indirectly--have now entered the clinic. However, only one adenosine receptor
      specific agent--the adenosine A2A receptor agonist regadenoson (Lexiscan;
      Astellas Pharma)--has so far gained approval from the US Food and Drug
      Administration (FDA). Here, we focus on the biology of adenosine signalling to
      identify hurdles in the development of additional pharmacological compounds
      targeting adenosine receptors and discuss strategies to overcome these
      challenges.

PMID- 23535939
TI  - What skills should simulation training in arthroscopy teach residents? A focus on
      resident input.
AB  - PURPOSE:    Our purpose was to identify what surgical skills trainees consider
      important to possess before performing in the operating room and the components
      of an optimal simulator. METHODS:    An online survey composed of 35 questions
      was completed by 67 orthopedic residents from across Canada. The questions
      examined the opinions of residents for their perspective on what constitutes an
      optimal design of an arthroscopic simulator. RESULTS:    The average year of
      residency of the respondents was 3.2, and the average number of arthroscopies
      assisted on was 66.1 with a range of 0-300. Identification of structures and
      navigation of the arthroscope were ranked highly in terms of importance for
      trainee surgeons to possess before performing in the operating room. Higher
      fidelity simulation models such as cadaveric specimens or the use of synthetic
      knees were preferred over lower fidelity simulation models such as virtual
      reality simulators or bench top models. CONCLUSION:    The information from
      trainees can be used in the development of a simulator for medical education as
      well as program and curriculum design. The report also highlights the importance
      of the pre-RCT phases leading to the development of the most effective simulation
      programs.

PMID- 23535940
TI  - Assessment of trace elements and stable isotopes of three Ardeid species at
      Birama Swamp, Cuba.
AB  - The Birama Swamp is the second largest wetland in the Caribbean region and it is
      inhabited by large populations of waterbirds. Here we report, for the first time,
      the foraging ecology and pollutant levels of three Ardeidae species: Cattle egret
      (Bubulcus ibis), Snowy egret (Egretta thula), and Tricolored heron (E. tricolor)
      breeding in this wetland using stable-isotope (delta (15)N and delta (13)C) and
      trace elements [mercury (Hg), lead (Pb), and selenium (Se)] analysis of chick
      feathers. Our results showed that individuals from all species occupied similar
      trophic levels. However, we found significant differences for delta (13)C, with
      the highest values in cattle egret indicating its use of terrestrial habitats and
      a generalist and opportunist behavior. No significant differences were found for
      Pb among species. Yet, Hg levels were greater and similar in tricolored heron and
      snowy egret than in cattle egret, which was associated with their greater use of
      aquatic environments. Snowy egret had the lowest values of Se differing
      significantly with the other two species suggesting a different relative use of
      prey type. Modeling log-Hg concentration in relation to delta (15)N and delta
      (13)C showed an independent and significant relationship among species but
      without interaction with species level indicating that within a particular
      species, higher Hg levels were associated with higher delta (15)N values. There
      was no interaction between delta (15)N and delta (13)C in the general linear
      models for Se and Pb in all species. We found an association between delta (15)N
      and species in Pb for snowy egret. The foraging habitat use of these species and
      the low levels of pollutants, which are lower than in other similar habitats in
      other areas of the world, indicated that there is not risk of negative effects in
      juvenile birds of the Birama Swamp colony that may impair their survival. Our
      results can be used as a baseline to achieve management regulations.

PMID- 23535941
TI  - Health risks associated with pesticide residues in sediments, fish, and plants
      from the Oueme Valley in the Republic of Benin.
AB  - To determine possible human and environmental health risks, organochlorine
      pesticide residues were determined in vegetables grown in floodplains along the
      Oueme River near Lowe in Benin. Testing of vegetables found 13 pesticides with
      SigmaDDT, alpha-endosulfan, Sigmadrin, and lindane being most important. The same
      pesticides were also detected in plants eaten by bovine cattle, sheep, and
      herbivorous fish. Human pesticide intake by vegetable consumption was compared
      with tolerable daily intake (TDI) values reported by the World Health
      Organization. Pesticide intake by fish consumption was estimated from residue
      levels in whole fish collected from the Oueme River in 2004 and reported earlier.
      Fish consumption does not pose a risk for human health, but consuming vegetables
      that contain pesticide residues may lead to exceedance of TDI values. Based on
      these findings, concerns are warranted, and more work is needed to understand the
      full exposure profile for the local population.

PMID- 23535943
TI  - A genetic and metabolic analysis revealed that cotton fiber cell development was
      retarded by flavonoid naringenin.
AB  - The cotton (Gossypium spp.) fiber is a unique elongated cell that is useful for
      investigating cell differentiation. Previous studies have demonstrated the
      importance of factors such as sugar metabolism, the cytoskeleton, and hormones,
      which are commonly known to be involved in plant cell development, while the
      secondary metabolites have been less regarded. By mining public data and
      comparing analyses of fiber from two cotton species (Gossypium hirsutum and
      Gossypium barbadense), we found that the flavonoid metabolism is active in early
      fiber cell development. Different flavonoids exhibited distinct effects on fiber
      development during ovule culture; among them, naringenin (NAR) could
      significantly retard fiber development. NAR is a substrate of flavanone 3
      hydroxylase (F3H), and silencing the F3H gene significantly increased the NAR
      content of fiber cells. Fiber development was suppressed following F3H silencing,
      but the overexpression of F3H caused no obvious effects. Significant retardation
      of fiber growth was observed after the introduction of the F3H-RNA interference
      segment into the high-flavonoid brown fiber G. hirsutum T586 line by cross. A
      greater accumulation of NAR as well as much shorter fibers were also observed in
      the BC1 generation plants. These results suggest that NAR is negatively
      associated with fiber development and that the metabolism mediated by F3H is
      important in fiber development, thus highlighting that flavonoid metabolism
      represents a novel pathway with the potential for cotton fiber improvement.

PMID- 23535944
TI  - Synthesis of 2-amino-imidazo[4,5-b]pyridines.
AB  - The C2 amination of imidazo[4,5-b]pyridines was accomplished through C2
      halogenation followed by substitution (SNAr) with functionalized primary and
      secondary amines. This regioselective sequence is operationally simple and
      provides an easy access to derivatives of protected imidazo[4,5-b]pyridines.

PMID- 23535945
TI  - [Eccrine poroma].
AB  - A 42-year-old man presented with a rapidly growing nodule on his right cheek.
      Except for some itching, it was asymptomatic. The tumor was excised with 3-4 mm
      safety margin. The clinical differential diagnostic considerations included
      pyogenic granuloma, amelanotic melanoma, basal cell carcinoma and eccrine poroma.
      An eccrine poroma is a rare tumor derived from the eccrine sweat gland. Hormonal
      disturbances, trauma, immunosuppression, actinic damages and radiotherapy have
      been suggested as possible etiologic factors; however, the exact pathophysiology
      remains unclear.

PMID- 23535942
TI  - Rhizobial infection is associated with the development of peripheral vasculature
      in nodules of Medicago truncatula.
AB  - Nodulation in legumes involves the coordination of epidermal infection by
      rhizobia with cell divisions in the underlying cortex. During nodulation,
      rhizobia are entrapped within curled root hairs to form an infection pocket.
      Transcellular tubes called infection threads then develop from the pocket and
      become colonized by rhizobia. The infection thread grows toward the developing
      nodule primordia and rhizobia are taken up into the nodule cells, where they
      eventually fix nitrogen. The epidermal and cortical developmental programs are
      synchronized by a yet-to-be-identified signal that is transmitted from the outer
      to the inner cell layers of the root. Using a new allele of the Medicago
      truncatula mutant Lumpy Infections, lin-4, which forms normal infection pockets
      but cannot initiate infection threads, we show that infection thread initiation
      is required for normal nodule development. lin-4 forms nodules with centrally
      located vascular bundles similar to that found in lateral roots rather than the
      peripheral vasculature characteristic of legume nodules. The same phenomenon was
      observed in M. truncatula plants inoculated with the Sinorhizobium meliloti exoY
      mutant, and the M. truncatula vapyrin-2 mutant, all cases where infections
      arrest. Nodules on lin-4 have reduced expression of the nodule meristem marker
      MtCRE1 and do not express root-tip markers. In addition, these mutant nodules
      have altered patterns of gene expression for the cytokinin and auxin markers CRE1
      and DR5. Our work highlights the coordinating role that bacterial infection
      exerts on the developing nodule and allows us to draw comparisons with primitive
      actinorhizal nodules and rhizobia-induced nodules on the nonlegume Parasponia
      andersonii.

PMID- 23535946
TI  - [Erlotinib-induced acneiform eruption].
AB  - A 73-year-old man has been suffering from a pulmonary adenocarcinoma for three
      years. He has been treated with the EGF-inhibitor erlotinib for the past 18
      months. While taking this medication he developed a progressive papulopustular
      rash on his face and trunk which later spread to his thighs. Topical treatment
      with methylprednisolone and nadifloxacin, as well as short courses of systemic
      doxycycline and ciprofloxacin, led to marked improvement and control of his skin
      condition.

PMID- 23535947
TI  - [Polypoid basal cell carcinoma].
AB  - The basal cell carcinoma is a malignant tumor which originates from the epidermal
      stem cells. The polypoid basal cell carcinoma is an uncommon variant. We report
      on a 70-year-old man with a red nodule on his left breast. Clinical and
      histopathologic criteria led to the diagnosis of polypoid basal cell carcinoma.
      This variant is characterized by exophytic, polypoid growth. Histologically, the
      aggregates of tumor cells are usually limited to the polypoid zone.

PMID- 23535948
TI  - Patterns of DNA methylation throughout a range expansion of an introduced
      songbird.
AB  - The spread of invasive species presents a genetic paradox: how do individuals
      overcome the genetic barriers associated with introductions (e.g., bottlenecks
      and founder effects) to become adapted to the new environment? In addition to
      genetic diversity, epigenetic variation also contributes to phenotypic variation
      and could influence the spread of an introduced species in novel environments.
      This may occur through two different (non-mutually exclusive) mechanisms.
      Individuals may benefit from existing (and heritable) epigenetic diversity or de
      novo epigenetic marks may increase in response to the new environment; both
      mechanisms might increase flexibility in new environments. Although epigenetic
      changes in invasive plants have been described, no data yet exist on the
      epigenetic changes throughout a range expansion of a vertebrate. Here, we used
      methylation sensitive-amplified fragment length polymorphism to explore genome
      wide patterns of methylation in an expanding population of house sparrows (Passer
      domesticus). House sparrows were introduced to Kenya in the 1950s and have
      significant phenotypic variation dependent on the time since colonization. We
      found that Kenyan house sparrows had high levels of variation in methylation
      across the genome. Interestingly, there was a significant, potentially
      compensatory relationship between epigenetic and genetic diversity: epigenetic
      diversity was negatively correlated with genetic diversity and positively
      correlated with inbreeding across the range expansion. Thus, methylation may
      increase phenotypic variation and/or plasticity in response to new environments
      and therefore be an important source of inter-individual variation for adaptation
      in these environments, particularly over the short timescales over which
      invasions occur. 

PMID- 23535949
TI  - Catalytic isomerization of allylic alcohols in water by [RuClCp(PTA)2],
      [RuClCp(HPTA)2]Cl2.2H2O, [RuCp(DMSO-kappaS)(PTA)2]Cl, [RuCp(DMSO
      kappaS)(PTA)2](OSO2CF3) and [RuCp(DMSO-kappaS)(HPTA)2]Cl3.2H2O.
AB  - The new water soluble complexes [RuClCp(HPTA)2]Cl2.2H2O (2), [RuCp(DMSO
      kappaS)(PTA)2]Cl (3), [RuCp(DMSO-kappaS)(PTA)2](OSO2CF3) (4) and [RuCp(DMSO
      kappaS)(HPTA)2]Cl3.2H2O (5) have been synthesized and fully characterized by NMR,
      IR and elemental analysis. The structures of complexes 2.2H2O and 5.2H2O were
      also characterized by single crystal X-ray determination. The catalytic activity
      of the complexes and [RuClCp(PTA)2] () for the isomerisation in water of 1-octen-
      to 1-penten-3-ol was assessed and discussed.

PMID- 23535951
TI  - Magnetic properties of cylindrical diameter modulated Ni80Fe20 nanowires:
      interaction and coercive fields.
AB  - Magnetic properties of cylindrical Ni80Fe20 nanowires with modulated diameters
      are investigated theoretically as a function of their geometrical parameters and
      compared with those produced inside the pores of anodic alumina membranes by
      pulsed electrodeposition. We observe that the Ni80Fe20 nanowires with modulated
      diameters reverse their magnetization via the nucleation and propagation of a
      vortex domain wall. The system begins generating vortex domains in the nanowire
      ends and in the transition region between the two segments to minimize
      magnetostatic energy generated by surfaces perpendicular to the initial
      magnetization of the sample. Besides, we observed an increase of the coercivity
      for the sample with equal volumes in relation to the sample with equal lengths.
      Finally, the interaction field is stronger in the case of constant volume
      segments. These structures could be used to control the motions of magnetic
      domain walls. In this way, these nanowires with modulated diameters can be an
      alternative to store information or even perform logic functions.

PMID- 23535952
TI  - Facile preparation and ultra-microporous structure of melamine-resorcinol
      formaldehyde polymeric microspheres.
AB  - A facile hydrothermal method was developed to synthesize nitrogen-rich phenolic
      microspheres with a tunable ultra-microporous structure for CO(2) adsorption. The
      results highlighted that chemical composition and ultramicroporous size, much
      more than surface area, dictated the CO(2) uptake in a microporous organic
      polymer.

PMID- 23535950
TI  - Development of diagnostic and treatment strategies for glaucoma through
      understanding and modification of scleral and lamina cribrosa connective tissue.
AB  - Considerable evidence indicates that the state of ocular connective tissues and
      their response in glaucomatous disease affect the degree of glaucoma damage. Both
      experimental and clinical data suggest that improved diagnostic and prognostic
      information can be derived from the assessment of the mechanical responsiveness
      of the sclera and lamina cribrosa to intraocular pressure (IOP). Controlled
      mutagenesis of the sclera has produced a mouse strain that is relatively
      resistant to increased IOP. Alteration of the baseline scleral state can be
      accomplished through either increased cross-linking of fibrillar components or
      their reduction. The sclera is a dynamic structure, altering its structure and
      behavior in response to IOP change. The biochemical pathways that control these
      responses are fertile areas for new glaucoma treatments. 

PMID- 23535955
TI  - [Colorectal cancer screening: where are we and where are we going?].
AB  - Colorectal cancer is a leading contributing cause of death for malignancy in the
      general population. An efficient screening policy would result in a remarkable
      decrease in cancer-related mortality since a benign, fully removable adenoma is
      the biologic precursor in the vast majority of cases. Endoscopy of the lower
      bowel and fecal occult blood test are considered relevant means of providing
      effective cancer screening and early diagnosis of benign cancer precursors.
      Compliance to screening programs is key to effective cancer screening. This
      review deals with colorectal cancer screening programs with a particular focus on
      the most recent national and international guidelines on cancer screening and
      follow-up policies.

PMID- 23535954
TI  - Ipilimumab alone or in combination with radiotherapy in metastatic castration
      resistant prostate cancer: results from an open-label, multicenter phase I/II
      study.
AB  - BACKGROUND: This phase I/II study in patients with metastatic castration
      resistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in
      combination with radiotherapy, based on the preclinical evidence of synergistic
      antitumor activity between anti-CTLA-4 antibody and radiotherapy. PATIENTS AND
      METHODS: In dose escalation, 33 patients (>=6/cohort) received ipilimumab every 3
      weeks * 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8
      Gy/lesion). The 10-mg/kg cohorts were expanded to 50 patients (ipilimumab
      monotherapy, 16; ipilimumab + radiotherapy, 34). Evaluations included adverse
      events (AEs), prostate-specific antigen (PSA) decline, and tumor response.
      RESULTS: Common immune-related AEs (irAEs) among the 50 patients receiving 10
      mg/kg +/- radiotherapy were diarrhea (54%), colitis (22%), rash (32%), and
      pruritus (20%); grade 3/4 irAEs included colitis (16%) and hepatitis (10%). One
      treatment-related death (5 mg/kg group) occurred. Among patients receiving 10
      mg/kg +/- radiotherapy, eight had PSA declines of >=50% (duration: 3-13+ months),
      one had complete response (duration: 11.3+ months), and six had stable disease
      (duration: 2.8-6.1 months). CONCLUSIONS: In mCRPC patients, ipilimumab 10 mg/kg
      +/- radiotherapy suggested clinical antitumor activity with disease control and
      manageable AEs. Two phase III trials in mCRPC patients evaluating ipilimumab 10
      mg/kg +/- radiotherapy are ongoing. ClinicalTrials.gov identifier: NCT00323882.

PMID- 23535956
TI  - [The complex interplay between health services administration, health
      professionals and patients. A challenge to take up].
AB  - The risk of loss of essential elements of our professionalism, such as sense of
      duty, altruism and collegiality, contributes to the difficulties in the interplay
      between health services administration, health professionals and patients. It is
      not enough to increase salaries or change organization models. It is also
      insufficient a generic reference to the values of our profession, but it is
      mandatory to overcome the self-referencing attitude of health professions.

PMID- 23535958
TI  - [The role of music therapy in impaired hearing recovery. A survey among
      professionals working with deaf children and between users].
AB  - In this study, two groups are interviewed: the first study includes a sample of
      60 physicians and health providers in the field of deafness, whose opinion on
      music therapy is collected by a specific questionnaire; the second involves 8
      parents of deaf children attending music therapy lessons, who are asked to give
      an evaluation on the effect of music therapy, based on the experience of their
      children. Results show that health professionals know very little about the
      rehabilitative effectiveness of music therapy, whereas the parents of deaf
      children give a positive evaluation on the psychological, behavioral and
      linguistic benefits that music therapy gives to their deaf children.

PMID- 23535957
TI  - [Parental alienation syndrome (PAS): unknown in medical settings, endemic in
      courts].
AB  - A purposed syndrome of so-called parental alienation (PAS), unsupported by any
      evidence-based data, unknown in medical settings, unquoted in medical books,
      absent in DSM and ICD, never demonstrated by controlled studies published in high
      scientific level journals, is rampant in Courts where it can lead to loose
      parental custody. During a divorce trial, almost always the mothers and the
      children, become joint in a sort of folie au deux, in a denigration campaign of
      ex-husband/father. From a review on this issue it seems evident its theoretical
      roots lie on a theory that justify gender violence and children sexual abuse. The
      bias that both of them are layers and that he children have not autonomy block
      their possibility of any defence in front of a Court. In severe cases, PAS
      becomes a new and efficient tool of intra-familiar violence. The treatment of
      severe cases is to stop any contact between mother and children. The resort to
      PAS in Courts must be strongly rejected.

PMID- 23535959
TI  - [Diagnosis of coronary microvascualar dysfunction in diabetic patients with
      cardiac syndrome X: comparison by current methods].
AB  - The study population included 208 patients with chest pain and uninjured coronary
      arteries that we split into two populations: diabetics (72 patients) and non
      diabetics (136 patients). We split patients with chest pain and uninjured
      coronary arteries that had a myocardial scintigraphy into two populations:
      patients with positive scintigraphy and negative. We calculated, on angiographic
      images of each patient, stored on suitable digital supports, Timi Frame Count
      (TFC), Myocardial Blush Grade (MBG) and Total Myocardial Blush Score (TMBS) using
      the protocol described by Gibson and Yusuf. On the basis of Yusuf's experience we
      imagined a new index: the Total Timi Frame Count as the sum of the three coronary
      Timi Frame Count. From our results we found a worse coronary microcirculation in
      diabetic patients with lower values of TFC, MBG and TMBS (p=0.02),compared with
      non- diabetics. New index TTFC is usually higher in diabetics than non-diabetic
      patients. Patients with positive scintigraphy had a worse TMBS than patients with
      a negative one, with a high statistical significance (p=0.003).We focused on the
      correlation between scintigraphy defect and angiography data in the arteries of
      ischemia relieved by nuclear imaging. The analysis showed that healthy vessels
      had a lower TFC than diseased vessels and therefore a better microcirculation
      with a high statistical significance (p=0.0001). According to the literature,
      diabetic population has a major microcirculation disease; moreover the study of
      microcirculation by coronary angiography and myocardial scintigraphy shows a good
      correlation between two methods.

PMID- 23535961
TI  - [Chronic conversion somatic disorder: a case report].
AB  - Conversion disorder is characterized by several neurological and internistical
      symptoms that cannot be explained by an organic cause, exacerbating after stress
      events. The course of this disorder is typically short: it usually lasts about
      two weeks, and only 20-25% of patients relapse in the following year. This paper
      aims to show the clinical history of a patient complaining conversion symptoms
      from 7 consecutive years.

PMID- 23535960
TI  - [Di George syndrome: not always a pediatric diagnosis].
AB  - We describe a delayed diagnosis of Di George syndrome, in a 51 yr-old woman, with
      past medical history of epilepsy, mental retardation, chronic psychosis,
      nephrocalcinosis. She presented facial dysmorphism, multiple encephalic
      calcifications, hypocalcemia and lymphopenia. A microdeletion of 22q 11.2 was
      detected by fluorescence in situ hybridization (FISH), confirming the clinical
      suspicion .

PMID- 23535962
TI  - [The PET/CT with 18F-fluorocholine in the diagnosis of gliomatosis cerebri type
      2].
AB  - In a patient with cerebral gliomatosis type II MRI revealed a large area of
      altered signal in the temporal region, parietal and occipital lobes associated
      with a single nodule with perilesional contrast enhancement, which showed
      increased uptake on PET/CT with 18F-FCH, characterizing heterogeneous cellularity
      of the tumor.

PMID- 23535963
TI  - [Role of echocardiography on the diagnosis is ventricular dyssynchrony in
      patients selected for cardiac resynchronization].
AB  - Currently, cardiac resynchronization therapy (CRT) is a treatment for heart
      failure refractory to optimized medical therapy. However, approximately 30% -45%
      of patients selected according to the guidelines, are "non responders" to CRT.
      Since the CRT is an invasive treatment, the candidates for such therapy should be
      carefully selected to ensure an optimal clinical benefit and instrumental.
      Despite its demonstrated effectiveness in reducing mortality and hospitalizations
      in patients with chronic heart failure on optimal medical therapy, the diagnosis
      of dyssynchrony is not easy. On the one hand, some echocardiographic indices have
      proved unreliable, other, more complex parameters still need to be validated
      before being implemented in clinical routine. The purpose of our paper is to
      evaluate echocardiographic techniques and not consolidated in patient response to
      CRT.

PMID- 23535964
TI  - [Radically resected pancreatic cancer and adjuvant treatment. A review of the
      literature].
AB  - Adjuvant therapy represents the gold standard treatment for radically resected
      pancreatic cancer. Results from randomized clinical trials confirmed the efficacy
      of adjuvant therapy for pancreatic cancer but did not define what is the "right
      choice" in terms of type of antiblastic drug (among gemcitabine, 5-fluorouracil
      or other drugs), role of polychemotherapy and chemoradiotherapy. The objective of
      our study was to evaluate the efficacy and toxicity of adjuvant chemotherapy and
      chemoradiotherapy for radically resected pancreatic cancer through a systematic
      review of literature data, emphasizing the benefits regarding overall survival,
      disease-free survival and toxicity.

PMID- 23535965
TI  - History of recurrent urinary tract infection is not predictive of abnormality on
      voiding cystourethrogram.
AB  - PURPOSE: The American Academy of Pediatrics recently recommended against routine
      voiding cystourethrograms (VCUGs) in children 2 to 24 months with initial febrile
      UTI, raising concern for delayed diagnosis and increased risk of UTI-related
      renal damage from vesicoureteral reflux (VUR). We assessed factors potentially
      associated with higher likelihood of abnormal VCUG, including UTI recurrence,
      which could allow for more judicious test utilization. METHODS: We
      retrospectively reviewed all initial VCUGs performed at Children's Hospital of
      Michigan between January and June, 2010. History of recurrent UTI was ascertained
      by evidence of two or more prior positive cultures or history of "recurrent UTI"
      on VCUG requisition. Outcomes assessed included rates of VUR or any urologic
      abnormality on VCUG. RESULTS: Two hundred and sixty-two patients met inclusion
      criteria. VUR was detected in 21.3 %, urologic abnormality including VUR in 27.4
      %. Degree of bladder distension, department of referring physician, study
      indication, positive documented urine culture, and history of recurrent UTI or
      UTI and other abnormality were all not associated with increased likelihood of
      VUR or any urologic abnormality on VCUG. CONCLUSION: VUR and VCUG abnormality are
      no more likely when performed after recurrent UTI or for UTI plus other
      abnormality. This reasons against postponing VCUG until after UTI recurrence, as
      positive findings are no more likely in this setting.

PMID- 23535966
TI  - Combined linkage analysis and exome sequencing identifies novel genes for
      familial goiter.
AB  - Familial goiter is a genetic disease showing heterogeneous expression. To
      identify causative genes, we investigated three multigenerational goiter families
      with an autosomal dominant inheritance pattern. We performed genome-wide linkage
      analysis on all the families, combined with whole-exome sequencing in two
      affected individuals from each family. For linkage analysis, we considered loci
      with logarithm of odds (LOD) scores >1.5 as candidate regions for identification
      of rare variants. In one of the families, we found two rare heterozygous missense
      variants, p.V56M in RGS12 and p.G37D in GRPEL1, which segregate with goiter and
      are both located within the same haplotype on 4p16. This haplotype was not
      observed in 150 controls. In the other two families, we identified two additional
      rare missense variants segregating with goiter, p.A551T in CLIC6 on 21q22.12 and
      p.V412A in WFS1 on 4p16. In controls, the minor allele frequency (MAF) of p.V412A
      in WFS1 was 0.017 while p.A551T in CLIC6 was not detected. All identified genes
      (RGS12, GRPEL1, CLIC6 and WFS1) show expression in the human thyroid gland,
      suggesting that they may play a role in thyroid gland function. Moreover, these
      four genes are novel with regard to their involvement in familial goiter,
      supporting genetic heterogeneity of this disease. 

PMID- 23535967
TI  - Using multiple measures for quantitative trait association analyses: application
      to estimated glomerular filtration rate.
AB  - Studies of multiple measures of a quantitative trait can have greater precision
      and thus statistical power compared with single-measure studies, but this has
      rarely been studied in the relation to quantitative trait measurement error
      models in genetic association studies. Using estimated glomerular filtration rate
      (eGFR), a quantitative measure of kidney function, as an example we constructed
      measurement error models of a quantitative trait with systematic and random error
      components. We then examined the effects on precision of the parameter estimate
      between genetic loci and eGFR, resulting from varying the correlation and
      contribution of the error components. We also compared the empirical results from
      three genome-wide association studies (GWAS) of kidney function in 9049 European
      Americans: a single measure model, a three-measure model of the same biomarker of
      kidney function and a six-measure model of different biomarkers of kidney
      function. Simulations showed that given the same amount of overall errors,
      inclusion of measures with less correlated systematic errors led to greater gain
      in precision. The empirical GWAS results confirmed that both the three- and six
      measure models detected more eGFR-associated genomic loci with stronger
      statistical association than the single-measure model despite some heterogeneity
      among the measures. Multiple measures of a quantitative trait can increase the
      statistical power of a study without additional participant recruitment. However,
      careful attention must be paid to the correlation of systematic errors and
      inconsistent associations when different biomarkers or methods are used to
      measure the quantitative trait. 

PMID- 23535970
TI  - C(60)-Bodipy dyad triplet photosensitizers as organic photocatalysts for
      photocatalytic tandem oxidation/[3+2] cycloaddition reactions to prepare
      pyrrolo[2,1-a]isoquinoline.
AB  - C(60)-Bodipy hybrids exhibiting strong absorption of visible light and long-lived
      triplet excited states were used as photocatalysts for tandem oxidation/[3+2]
      cycloaddition of tetrahydroisoquinoline with N-phenylmaleimide to produce
      pyrrolo[2,1-a]isoquinolines. The reaction is substantially accelerated, compared
      to that catalyzed by Ru(bpy)(3)Cl(2).

PMID- 23535969
TI  - Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic
      syndrome.
AB  - Metabolic syndrome (MetS) is a common multifactorial disorder that involves
      abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Genome-wide
      association studies have identified a major risk locus for coronary artery
      disease and myocardial infarction on chromosome 9p21. Here, we examined the
      frequency of single nucleotide polymorphisms (SNPs) on chromosome 9p21 in a
      sample of Turkish patients with MetS and further investigated the correlation
      between regional SNPs, haplotypes, and MetS. The real-time polymerase chain
      reaction (RT-PCR) was used to analyze 4 SNPs (rs10757274 A/G, rs2383207 A/G,
      rs10757278 A/G, rs1333049 C/G) in 291 MetS patients and 247 controls. Analysis of
      4 SNPs revealed a significant difference in the genotype distribution for
      rs2383207, rs10757278, and rs1333049 between MetS patients and controls (p =
      0.041, p = 0.005, p = 0.023, respectively) but not for rs10757274 (p = 0.211).
      MetS and control allelic frequencies for rs2383207, rs10757278, and rs1333049
      were statistically different (p < 0.05). The rs2383207 AG variant, was identified
      as a MetS risk factor (p = 0.012, OR = 33.271; 95 % CI: 2.193-504.805) and the AA
      haplotype in block 1 and the GC, AG haplotypes in block 2 were associated with
      MetS (chi(2) = 3.875, p = 0.049; chi(2) = 9.334, p = 0.0022; chi (2) = 9.134, p =
      0.0025, respectively). In this study, we found that chromosome 9p21 SNP
      rs10757278 and related haplotypes correlate with MetS risk. This is the first
      report showing an association between a 9p21 variant and MetS and suggests that
      rs10757278 polymorphism may confer increased risk for disease.

PMID- 23535968
TI  - Informing family members of individuals with Lynch syndrome: a guideline for
      clinical geneticists.
AB  - The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer
      through periodic colonoscopies and removal of premalignant lesions in susceptible
      individuals. Therefore, predisposed individuals identified by mutation analysis
      are advised to inform their at-risk relatives about the options of predictive DNA
      testing and preventive measures. However, it has now been established that more
      than half of these relatives do not receive the necessary information. Barriers
      in conveying information include family communication problems and variable
      attitudes and practice among clinical geneticists. In this complex field, both
      medical, psychological, ethical and juridical aspects deserve consideration. Here
      we summarize the development of a revised guideline for clinical geneticists that
      allows a more active role of the geneticist, aimed at improving procedures to
      inform family members in Lynch syndrome and other hereditary and familial cancer
      syndromes. 

PMID- 23535971
TI  - Regulatory fit messages and physical activity motivation.
AB  - Targeted communication about health behaviors seems to be more effective than
      mass communication in which undifferentiated audiences receive identical
      messages. Regulatory focus is psychological variable that can be used to build
      two target groups: promotion-focused or prevention-focused people. It is
      hypothesized that targeting messages to an individual's regulatory focus creates
      regulatory fit and is more successful to promote a physically active lifestyle
      than nonfit messages. Two different print messages promoting a physically active
      lifestyle derived from regulatory focus theory (promotion message vs. prevention
      message) were randomly assigned to N = 98 participants after measuring their
      regulatory focus. It was examined whether regulatory fit between the regulatory
      focus and the assigned print message would lead to more positive evaluations in
      the dependent variables inclination toward the message (preference for the
      message), intention to perform the behavior, prospective and retrospective
      feelings associated with the behavior (positive and negative), and perceived
      value of the behavior directly after reading the message. Hierarchical linear
      regression analyses revealed that regulatory fit led to stronger intentions in
      the prevention-message condition and more prospective positive and retrospective
      positive feelings associated with the behavior in the promotion-message condition
      in contrast to the nonfit conditions. Prospective positive feelings associated
      with the behavior mediated the effect of regulatory fit on intention. The results
      partly provided support for the regulatory fit concept. Matching print messages
      to the regulatory focus of individuals seems to be a useful approach to enhance
      physical activity motivation. Future studies should include an objective measure
      of physical activity behavior.

PMID- 23535972
TI  - The effects of individual and team competitions on performance, emotions, and
      effort.
AB  - It is well documented that competition can affect performance and emotion in
      sport. However, our understanding of the comparative effects of individual and
      team competitions on performance and emotion is limited. We also know little
      about emotion-based mechanisms underlying the effects of different types of
      competition on performance. To address these issues, 64 participants completed a
      handgrip endurance task during time-trial, one-on-one, two-on-two, and four-on
      four competitions while self-report and possible corroborative physiological
      measures of enjoyment, anxiety, and effort were assessed. Results indicated that
      performance, enjoyment, anxiety, and effort increased from individual to team
      competitions. The observed increases in performance were mediated by increased
      enjoyment and effort. Our findings illustrate differential effects of individual
      and team competitions on performance and emotion. Moreover, they indicate that
      both enjoyment-based and anxiety-based mechanisms can explain changes in
      performance among different types of individual and team competition.

PMID- 23535973
TI  - Perceptual-cognitive skills and their interaction as a function of task
      constraints in soccer.
AB  - The ability to anticipate and to make decisions is crucial to skilled performance
      in many sports. We examined the role of and interaction between the different
      perceptual-cognitive skills underlying anticipation and decision making. Skilled
      and less skilled players interacted as defenders with life-size film sequences of
      11 versus 11 soccer situations. Participants were presented with task conditions
      in which the ball was located in the offensive or defensive half of the pitch
      (far vs. near conditions). Participants' eye movements and verbal reports of
      thinking were recorded across two experiments. Skilled players reported more
      accurate anticipation and decision making than less skilled players, with their
      superior performance being underpinned by differences in task-specific search
      behaviors and thought processes. The perceptual-cognitive skills underpinning
      superior anticipation and decision making were shown to differ in importance
      across the two task constraints. Findings have significant implications for those
      interested in capturing and enhancing perceptual-cognitive skill in sport and
      other domains.

PMID- 23535974
TI  - An attachment theory perspective in the examination of relational processes
      associated with coach-athlete dyads.
AB  - The aim of the current study was to examine actor and partner effects of (a)
      athletes' and coaches' attachment styles (avoidant and anxious) on the quality of
      the coach-athlete relationship, and (b) athletes' and coaches' quality of the
      coach-athlete relationship on relationship satisfaction employing the actor
      partner interdependence model (Kenny, Kashy, & Cook, 2006). Coaches (N = 107) and
      athletes (N = 107) completed a questionnaire related to attachment styles,
      relationship quality, and relationship satisfaction. Structural equation model
      analyses revealed (a) actor effects for coaches' and athletes' avoidant
      attachment styles on their own perception of relationship quality and coaches'
      and athletes' perception of relationship quality on their own perception of
      relationship satisfaction, and (b) partner effects for athletes' avoidant
      attachment style on coaches' perceptions of relationship quality and for coaches'
      perceptions of relationship quality on athletes' perceptions of relationship
      satisfaction. The findings highlight that attachments styles can help us
      understand the processes involved in the formation and maintenance of quality
      relational bonds between coaches and athletes.

PMID- 23535975
TI  - Effects of multiple concussions on retired national hockey league players.
AB  - The purpose of this study was to understand the meanings and lived experiences of
      multiple concussions in professional hockey players using hermeneutic,
      idiographic, and inductive approaches within an interpretative phenomenological
      analysis. The interviewer was an athlete who had suffered multiple concussions,
      and the interviewees were five former National Hockey League athletes who had
      retired due to medically diagnosed concussions suffered during their careers. The
      men discussed the physical and psychological symptoms they experienced as a
      result of their concussions and how the symptoms affected their professional
      careers, personal relationships, and quality of life. The former professional
      athletes related these symptoms to the turmoil that is ever present in their
      lives. These findings are of interest to athletes, coaches, sport administrators,
      family members, sport psychology practitioners, and medical professionals, as
      they highlight the severity of short- and long-term effects of concussions.

PMID- 23535976
TI  - Development and validation of the organizational stressor indicator for sport
      performers (OSI-SP).
AB  - The series of related studies reported here describe the development and
      validation of the Organizational Stressor Indicator for Sport Performers (OSI
      SP). In study 1, an expert and usability panel examined the content validity and
      applicability of an initial item pool. The resultant 96 items were analyzed with
      exploratory factor analyses in Study 2, with the factorial structure comprising 5
      factors (viz., goals and development, logistics and operations, team and culture,
      coaching, selection) and 33 items. Using confirmatory factor analyses, Studies 3
      and 4 found support for the 5-factor structure. Study 4 also provided evidence
      for the OSI-SP's concurrent validity and invariance across different groups. The
      OSI-SP is proposed as a valid and reliable measure of the organizational
      stressors encountered by sport performers.

PMID- 23535977
TI  - The influence of self-generated emotions on physical performance: an
      investigation of happiness, anger, anxiety, and sadness.
AB  - The present study examined the relationship between self-generated emotions and
      physical performance. All participants took part in five emotion induction
      conditions (happiness, anger, anxiety, sadness, and an emotion-neutral state) and
      we investigated their influence on the force of the finger musculature
      (Experiment 1), the jump height of a counter-movement jump (Experiment 2), and
      the velocity of a thrown ball (Experiment 3). All experiments showed that
      participants could produce significantly better physical performances when
      recalling anger or happiness emotions in contrast to the emotion-neutral state.
      Experiments 1 and 2 also revealed that physical performance in the anger and the
      happiness conditions was significantly enhanced compared with the anxiety and the
      sadness conditions. Results are discussed in relation to the Lazarus (1991,
      2000a) cognitive-motivational-relational (CMR) theory framework.

PMID- 23535978
TI  - Can stereotype threat affect motor performance in the absence of explicit
      monitoring processes? Evidence using a strength task.
AB  - Previous evidence shows that stereotype threat impairs complex motor skills
      through increased conscious monitoring of task performance. Given that one-step
      motor skills may not be susceptible to these processes, we examined whether
      performance on a simple strength task may be reduced under stereotype threat.
      Forty females and males performed maximum voluntary contractions under
      stereotypical or nullified-stereotype conditions. Results showed that the
      velocity of force production within the first milliseconds of the contraction
      decreased in females when the negative stereotype was induced, whereas maximal
      force did not change. In males, the stereotype induction only increased maximal
      force. These findings suggest that stereotype threat may impair motor skills in
      the absence of explicit monitoring processes, by influencing the planning stage
      of force production.

PMID- 23535979
TI  - When do chronic differences in self-regulation count? Regulatory focus effects in
      easy and difficult soccer tasks.
AB  - Research on regulatory focus theory (Higgins, 1997) suggests that performance
      increases if instructions fit with sportspersons' dispositions. Sportspersons who
      chronically focus on wins (i.e., promotion-oriented individuals) perform best if
      instructions frame the objective as a promotion goal (e.g., "Try to hit!"). By
      contrast, sportspersons who chronically focus on losses (i.e., prevention
      oriented individuals) perform best if instructions frame the objective as a
      prevention goal (e.g., "Try not to miss!"). Recent theorizing also suggests that
      regulatory focus interacts with task difficulty. In an experiment, we assessed
      soccer performance as a function of chronic focus, instructional focus, and task
      difficulty. Results support that task difficulty moderates the effects of fit on
      performance; fitting instructions to match the sportsperson's chronic regulatory
      focus improved performance in the easy rather than the difficult task. Findings
      are discussed regarding the role of regulatory fit in altering subjective
      pressure during sports performance.

PMID- 23535980
TI  - The significance and impact of Wade's rules.
AB  - The emergence of a set of simple yet powerful electron counting rules following a
      classic paper by Wade published in 1971 in J. Chem. Soc. D has transformed the
      way chemists think about the structures of clusters with delocalised skeletal
      bonding.

PMID- 23535981
TI  - CRISPRs of Enterococcus faecalis and E. hirae isolates from pig feces have
      species-specific repeats but share some common spacer sequences.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) are currently
      a topic of interest in microbiology due to their role as a prokaryotic immune
      system. Investigations of CRISPR distribution and characterization to date have
      focused on pathogenic bacteria, while less is known about CRISPR in commensal
      bacteria, where they may have a significant role in the ecology of the microbiota
      of humans and other animals, and act as a recorder of interactions between
      bacteria and viruses. A combination of PCR and sequencing was used to determine
      prevalence and distribution of CRISPR arrays in Enterococcus faecalis and
      Enterococcus hirae isolates from the feces of healthy pigs. Both type II CRISPR
      Cas and Orphan CRISPR (without Cas genes) were detected in the 195 isolates
      examined. CRISPR-Cas was detected in 52 (46/88) and 42 % (45/107) E. faecalis and
      E. hirae isolates, respectively. The prevalence of Orphan CRISPR arrays was
      higher in E. faecalis isolates (95 %, 84/88) compared with E. hirae isolates (49
      %, 53/107). Species-specific repeat sequences were identified in Orphan CRISPR
      arrays, and 42 unique spacer sequences were identified. Only two spacers matched
      previously characterized pig virome sequences, and many were apparently derived
      from chromosomal sequences of enterococci. Surprisingly, 17 (40 %) of the spacers
      were detected in both species. Shared spacer sequences are evidence of a lack of
      species specificity in the agents and mechanisms responsible for integration of
      spacers, and the abundance of spacer sequences corresponding to bacterial
      chromosomal sequences reflects interspecific interactions within the intestinal
      microbiota.

PMID- 23535982
TI  - Strong NH...S hydrogen bonds in molybdoenzyme models containing anilide moieties.
AB  - Monooxomolybdenum(IV) and dioxomolybdenum(VI) benzenedithiolate derivatives
      containing anilide moieties were synthesized and characterized by (1)H NMR, UV
      visible, IR, and Raman spectroscopies. These complexes exhibit very strong
      intramolecular NH...S hydrogen bonds formed by the acidic anilide NH proton and
      the desired coplanar structure, resulting in significantly positive redox
      potential and remarkable acceleration in the reduction of Me3NO in DMF.

PMID- 23535983
TI  - Synthesis of tetrasubstituted benzenes via rhodium(I)-catalysed ring-opening
      benzannulation of cyclobutenols with alkynes.
AB  - A formal [4 + 2] annulation occurs between 1,3-disubstituted cyclobutenols and
      internal alkynes in the presence of rhodium(I) catalysts to afford 1,2,3,5
      tetrasubstituted benzenes. These benzannulation products are generated through
      dehydration of the initially formed cyclohexadienols.

PMID- 23535984
TI  - Economic evaluation of nurse-led intensive care follow-up programmes compared
      with standard care: the PRaCTICaL trial.
AB  - OBJECTIVE: Following intensive care discharge, many patients suffer severe
      physical and psychological morbidity and a continuing high use of health
      services. Follow-up programmes have been proposed to improve the outcomes for
      these patients. We tested the hypothesis that nurse-led intensive care follow-up
      programmes are cost-effective. METHODS: A pragmatic, multicentre, randomised
      controlled trial of nurse-led intensive care unit follow-up programmes versus
      standard care. A cost-utility analysis was conducted after 12 months' follow-up
      to compare the two interventions. Costs were assessed from the perspective of the
      UK NHS and outcomes were measured in quality-adjusted life years (QALYs) based
      upon responses to the EQ-5D administered at baseline, 6 and 12 months. RESULTS: A
      total of 286 patients were recruited to the trial. Total mean cost was L 5,789
      for standard care and L 7,577 for the discharge clinic. The adjusted difference
      in means was L 2,435 [95 % confidence interval (CI) -297 to 5,566]. Mean QALYs
      were 0.58 for standard care and 0.60 for the discharge clinic. The adjusted mean
      difference was -0.003 (95 % CI -0.066 to 0.060). If society were willing to pay L
      20,000 per QALY then there would be a 93 % chance that standard care would be
      considered most efficient. CONCLUSIONS: A nurse-led intensive care unit (ICU)
      follow-up programme showed no evidence of being cost-effective at 12 months.
      Further work should focus on evidence-based development of discharge clinic
      services and current ICU follow-up programmes should review their practice in
      light of these results.

PMID- 23535986
TI  - How to understand a woman's obligations to the fetus in unwanted pregnancies.
AB  - Some have challenged Thomson's case of the famous unconscious violinist (UV) by
      arguing that in cases of consensual sex a woman is partially morally responsible
      for the existence of a needy fetus; since she is partially responsible she ought
      to assist the fetus, and so abortion is morally wrong. Call this the
      Responsibility Objection (RO) to UV. In this paper, I briefly criticize one of
      the most widely discussed objections to RO and then suggest a new way to
      challenge RO. In so doing, I investigate the plausibility of the moral principle
      that appears to be driving RO: If a woman is partially morally responsible for
      the existence of a needy fetus, she has a moral obligation to assist the fetus. I
      argue that this principle is false. I suggest modified versions of this principle
      but argue that, even on the most plausible version, RO does not persuade.

PMID- 23535985
TI  - Pitfalls in diagnosing and treating children with renal artery hypertension.

PMID- 23535987
TI  - Relationships between metrics of visit-to-visit variability of blood pressure.
AB  - This paper examines relationships between metrics of visit-to-visit variability
      (VVV) of blood pressure (BP) to determine which metrics should be calculated in
      studies of the association of VVV with health outcomes. We examined correlation
      and agreement between quintiles for standard deviation (s.d.), standard deviation
      independent of the mean (SDIM), coefficient of variation (CV), successive
      variation (SV), average real variability (ARV), range, maximum, peak size and
      trough size of systolic BP in the Trial of Preventing Hypertension placebo arm
      (n=288). The average age of participants was 48 years. Mean systolic BP was 133.5
      mm Hg. VVV metrics were all significantly correlated (P<0.001). Correlations
      between s.d., SDIM, CV and range and between ARV and SV were >=0.90. Kappa
      statistics between quintiles of SD, SDIM, CV and range and between ARV and SV
      were >=0.80. In studies of the relationship of VVV with health outcomes, we
      recommend reporting results for one of the metrics of overall variability (s.d.,
      SDIM, CV), one of the metrics of variability between consecutive visits (SV,
      ARV), and one or more of the metrics of extreme values at a single visit
      (maximum, peak size, trough size).

PMID- 23535988
TI  - Diastolic blood pressure reduction contributes more to the regression of left
      ventricular hypertrophy: a meta-analysis of randomized controlled trials.
AB  - Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor;
      however, the key strategy necessary for LVH regression in hypertensive patients
      is not clear. A meta-analysis was conducted to study the effect of blood pressure
      reduction on LVH regression. We explored the relationship between different
      degrees of systolic blood pressure (SBP)/diastolic blood pressure (DBP) reduction
      and LVH regression. A total of 17 randomized controlled trials comprising 2196
      hypertensive patients (mean age, 56.3 years; 64.1% were men) were identified.
      Different degrees of SBP and DBP reductions were significantly associated with
      LVH regression: SBP reduction >=20  mm  Hg (SBPM20) (weighted mean difference
      (WMD): 14.35  g  m(-2); 95% confidence interval (CI): 10.44, 18.26; P<0.0001);
      SBP reduction <20  mm  Hg (SBPL20 group) (WMD: 14.82  g  m(-2); 95% CI: 9.83,
      19.8(2); P<0.0001); DBP reduction >=10  mm  Hg (DBPM10 group) (WMD: 15.17 g m(
      2); 95% CI: 11.86, 18.48; P<0.0001); and DBP reduction <10  mm  Hg (DBPL10 group)
      (WMD: 11.76  g  m(-2); 95% CI: 3.75, 19.76; P=0.004). Significant regression of
      LVH was found in the DBPM10 group compared with the SBPM20, SBPL20 and DBPL10
      groups (P<0.0001). The most significant decrease in LVH was seen in patients with
      a mean age over 60 years in the DBPM10 group. Moreover, the renin-angiotensin
      system inhibitor was found to be the most effective antihypertensive drug for LVH
      regression. This meta-analysis result indicates that proper DBP reduction plays
      an important role in the regression of echocardiographic LVH in hypertensive
      patients.

PMID- 23535989
TI  - Higher leptin is associated with hypertension: the Multi-Ethnic Study of
      Atherosclerosis.
AB  - Adipokines are secreted from adipose tissue, influence energy homeostasis and may
      contribute to the association between obesity and hypertension. Among 1897
      participants enrolled in the Multi-Ethnic Study of Atherosclerosis, we examined
      associations between blood pressure and leptin, tumor necrosis factor-alpha
      (TNFalpha), resistin and total adiponectin. The mean age and body mass index
      (BMI) was 64.7 years and 28.1, respectively, and 50% were female. After
      adjustment for risk factors, a 1-s.d.-increment higher leptin level was
      significantly associated with higher systolic (5.0 mm Hg), diastolic (1.9), mean
      arterial (2.8) and pulse pressures (3.6), as well as a 34% higher odds for being
      hypertensive (P<0.01 for all). These associations were not materially different
      when the other adipokines, as well as BMI, waist circumference or waist-to-hip
      ratio, were additionally added to the model. Notably, the associations between
      leptin and hypertension were stronger in men, but were not different by
      race/ethnic group, BMI or smoking status. Adiponectin, resistin and TNFalpha were
      not independently associated with blood pressure or hypertension. Higher serum
      leptin, but not adiponectin, resistin or TNFalpha, is associated with higher
      levels of all measures of blood pressure, as well as a higher odds of
      hypertension, independent of risk factors, anthropometric measures and other
      selected adipokines. 

PMID- 23535990
TI  - Central blood pressure in the management of hypertension: soon reaching the goal?
AB  - Blood pressure (BP) is conventionally measured by cuff at the brachial artery as
      an indication of pressure experienced by the organs. However, individual
      variation in pulse pressure amplification means that brachial cuff BP may be a
      poor representation of true central BP. Estimation of central BP is now possible
      using non-invasive methods that are amenable for widespread use. This paper
      reviews the evidence regarding the potential value of central BP in hypertension
      management. The major lines of evidence that support the use of central BP as a
      clinical tool include the: (1) major discrepancies in central BP among people
      with similar brachial BP; (2) independent relationship of central BP with end
      organ damage; (3) independent relationship of central BP with cardiovascular (CV)
      events and mortality; (4) differential central and brachial BP responses to
      antihypertensive medications and; (5) improvements in end-organ damage after
      therapy more strongly relate to central than brachial BP. Despite all this,
      important evidence gaps relating to clinical use of central BP need fulfilling.
      These include the lack of central BP reference values and randomized, controlled
      studies to determine if: (1) central BP can help with diagnostic/therapeutic
      decisions and; (2) CV outcome is improved by targeting therapy towards lowering
      central BP levels. Additional challenges such as standardization of central BP
      methods, and understanding which patients are most likely to benefit from central
      BP monitoring also need to be determined. Overall, the future for central BP as a
      worthwhile clinical instrument appears positive, but there is much to be done.

PMID- 23535991
TI  - Inflammation does not influence arterial stiffness and pulse-wave velocity in
      patients with coronary artery disease.
AB  - Vascular function is an important pathophysiological factor in cardiovascular
      disease, and is influenced by many factors, one of the principles being
      hypertension. Developing evidence suggests that inflammation may be another risk
      factor. Vascular function and blood pressure haemodynamics can be assessed by
      arterial stiffness, pulse pressure and plasma markers. Testing the hypothesis of
      a relationship between inflammatory markers, hypertension and vascular function,
      we recruited 222 stable coronary artery disease outpatients, assessing
      inflammation with levels of high sensitivity CRP and interleukin-6 (IL-6),
      vascular function/arterial stiffness by pulse-wave velocity (PWV), augmentation
      (SphygmoCor system Artcor, Sidney, Australia), aortic and brachial artery pulse
      pressure, Von Willebrand factor (vWf) and soluble E-selectin (both enzyme-linked
      immunosorbent assay). In multivariate regression analysis, PWVs, augmentation
      indices and pulse pressures were linked with age, blood pressure and (some) with
      heart rate (all P<0.01), while vWf was associated with age (P=0.01). We conclude
      that, in patients with stable coronary artery disease, arterial stiffness and
      pulse pressure are related strongly and independently with age, blood pressure
      and heart rate, and that any effect of inflammation is minimal.

PMID- 23535993
TI  - Plasmonic-driven thermal sensing: ultralow detection of cancer markers.
AB  - This communication describes an ultrafast high-sensitivity plasmonic-driven
      thermal sensing approach for the detection of tumoral markers. Gold nanoprisms
      derivatized with antibody against carcinoembryonic antigen (anti-CEA) are used to
      label CEA molecules and imprint thermal signals upon illumination, enabling
      sensitivities up to the attomolar range in real patient samples.

PMID- 23535994
TI  - Improving access to medicines in low and middle income countries: corporate
      responsibilities in context.
AB  - More than two billion people in low- and middle-income countries (LMIC) lack
      adequate access to essential medicines. In this paper, we make strong public
      health, human rights and economic arguments for improving access to medicines in
      LMIC and discuss the different roles and responsibilities of key stakeholders,
      including national governments, the international community, and non-governmental
      organizations (NGOs). We then establish a framework of pharmaceutical firms'
      corporate responsibilities - the "must," the "ought to," and the "can" dimensions
      - and make recommendations for actionable business strategies for improving
      access to medicines. We discuss controversial topics, such as pharmaceutical
      profits and patents, with the goal of building consensus around facts and working
      towards a solution. We conclude that partnerships and collaboration among
      multiple stakeholders are urgently needed to improve equitable access to
      medicines in LMIC.

PMID- 23535992
TI  - The combination of carmustine wafers and temozolomide for the treatment of
      malignant gliomas. A comprehensive review of the rationale and clinical
      experience.
AB  - Current treatment strategies in patients with newly-diagnosed glioblastoma
      include surgical resection with post-operative radiotherapy and
      concomitant/adjuvant temozolomide (the "Stupp protocol") or resection with
      implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the
      surgical cavity followed by radiotherapy. In clinical practice, patients with
      malignant glioma treated with BCNU wafer often also receive adjuvant
      temozolomide. However, current treatment guidelines are unclear on whether and
      how these treatment practices can be combined, and no prospective phase 3 study
      has assessed the safety and efficacy of combining BCNU wafers with temozolomide
      and radiation in high-grade malignant glioma. The rationale for multimodal
      therapy comprising surgical resection with adjunct local BCNU wafers followed by
      radiotherapy and temozolomide is based on complementary and synergistic
      mechanisms of action between BCNU and temozolomide in preclinical studies; a
      shared primary resistance pathway, methylguanine-DNA methyltransferase (MGMT);
      and the opportunity to overcome resistance through MGMT depletion to boost
      cytotoxic activity. A comprehensive review of the literature identified 19
      retrospective and prospective studies investigating the use of this multimodal
      strategy. Median overall survival in 14 studies of newly-diagnosed patients
      suggested a modest improvement versus resection followed by Stupp protocol or
      resection with BCNU wafers, with an acceptable and manageable safety profile.

PMID- 23535995
TI  - Nanocomposites of silver nanoparticles embedded in glass nanofibres obtained by
      laser spinning.
AB  - Nanocomposites made of non-woven glass fibres with diameters ranging from tens of
      nanometers up to several micrometers, containing silver nanoparticles, were
      successfully fabricated by the laser spinning technique. Pellets of a soda-lime
      silicate glass containing silver nanoparticles with varying concentrations (5 and
      10 wt%) were used as a precursor. The process followed to obtain the silver
      nanofibres did not agglomerate significantly the metallic nanoparticles, and the
      average particle size is still lower than 50 nm. This is the first time that
      glass nanofibres containing silver nanoparticles have been obtained following a
      process different from electrospinning of a sol-gel, thus avoiding the
      limitations of this method and opening a new route to composite nanomaterials.
      Antibacterial efficiency of the nanosilver glass fibres, tested against one of
      the most common gram negative bacteria, was greater than 99.99% compared to the
      glass fibres free of silver. The silver nanoparticles are well-dispersed not only
      on the surface but are also embedded into the uniform nanofibres, which leads to
      a long lasting durable antimicrobial effect. All these novel characteristics will
      potentially open up a whole new range of applications.

PMID- 23535996
TI  - Leptospirosis risk increases with changes in species composition of rat
      populations.
AB  - Rats are major reservoirs of leptospirosis and considered as a main threat to
      biodiversity. A recent introduction of Rattus rattus to the island of Futuna
      (Western Polynesia) provided the opportunity to test if a possible change in
      species composition of rat populations would increase the risk of leptospirosis
      to humans. We trapped rodents on Wallis and Futuna and assessed Leptospira
      carriage in 357 rodents (Rattus norvegicus, R. rattus, Rattus exulans, and Mus
      domesticus) from 2008 to 2012. While Leptospira prevalence in rodents and the
      composition of rat populations on Futuna fluctuated with rainfall, the biomass of
      Leptospira-carrying rodents has been continuously rising from 2008 to 2012. Our
      results suggest that the introduction of R. rattus increases the risk to humans
      being infected with leptospirosis by rats.

PMID- 23535997
TI  - Homologue of Sox10 in Misgurnus anguillicaudatus: sequence, expression pattern
      during early embryogenesis.
AB  - A number of genetic studies have established that Sox10 is a transcription factor
      associated with neurogenesis in vertebrates. We have isolated a homologue of
      Sox10 gene from the brain of Misgurnus anguillicaudatus by using homologous
      cloning and RACE method, designated as MaSox10b. The full-length cDNA of MaSox10b
      contained a 311 bp 5'UTR, a 312 bp 3'UTR and an ORF encoding a putative protein
      of 490 amino acids with a characteristic HMG-box DNA-binding domain of 79 amino
      acids (aa: 105-183). Phylogenetic tree shows that the MaSOX10b fits within the
      Sox10 clade and clusters firmly into Sox10b branches. During embryogenesis,
      MaSox10b was first detected in gastrulae stage. From somitogenesis stage and
      thereafter, distinct expression was observed in the medial neural tube, extending
      from the hindbrain through the posterior trunk. Taken together, these preliminary
      findings suggested that MaSox10b is highly conserved during vertebrate evolution
      and involved in a wide range of developmental processes including embryogenesis
      and neurogenesis.

PMID- 23535998
TI  - Anomalous diffusion of TePixD and identification of the photoreaction product.
AB  - TePixD is a blue-light sensor protein from the thermophilic cyanobacterium
      Thermosynechococcus elongatus BP-1 (TePixD Tll0078). Although the photochemistry
      has been examined, so far the photoproduct remains unknown. We have measured the
      diffusion coefficient (D) of TePixD in the dark by dynamic light scattering and
      have discovered a very peculiar diffusion property; the decamer oligomer has a
      larger D than that of the pentamer. Furthermore, D of the pentamer was found to
      be very close to that of the TePixD decamer photoreaction product. In order to
      investigate this reaction further, elution profiles of size-exclusion
      chromatography were measured under dark and illuminated conditions at low (40
      MUM) and high (1.1 mM) TePixD concentrations. On the basis of these results, we
      have concluded that the main photoreaction of the TePixD decamer is the
      dissociation into the pentamer. The secondary structure change associated with
      this reaction was found to be minor according to circular dichroism analysis.

PMID- 23535999
TI  - Results of platinum-based chemotherapy in unselected performance status (PS) 2
      patients with advanced non-small cell lung cancer: a cohort study.
AB  - Recent phase-III trials show that platinum-based chemotherapy (PBCT) for patients
      with advanced non-small cell lung cancer and poor performance status (PS)
      improves survival without increasing toxicity, compared to single-agent
      chemotherapy (CT). The aim of this study was to asses whether these results are
      transposable in a community population. About 260 consecutive patients with stage
      IIIB-IV NSCLC (25 % with PS 2) receiving a PBCT were prospectively included in
      the study and retrospectively analyzed. No difference was observed between PS 0-1
      and 2 patients regarding tumor-control rate, symptom relief, and grade III-V
      toxicity. Median and 1-year survival of PS 2 patients was 6.2 months and 32 %,
      respectively. PS 1 and PS 2 patients continuing first-line CT beyond the first
      course shared the same survival. On the other hand, more PS 2 (31.8 vs. 9.3 % of
      PS 0-1 patients, p < 0.001) discontinued first-line CT after the first course
      with a poor clinical outcome. They were more likely to have lost weight and to
      have a high comorbidity score. PBCT in unselected PS 2 patients achieved survival
      rates similar to those observed in clinical trials, with no increase in toxicity.
      PS 2 patients continuing CT beyond the first course shared the same prognosis
      than PS 1 patients. However, almost one-third of PS 2 patients discontinued CT
      after the first course. Their prognosis was poor.

PMID- 23536000
TI  - Study of critical role of c-Met and its inhibitor SU11274 in colorectal
      carcinoma.
AB  - c-Met plays an important role in colorectal tumorigenesis and disease progression
      and thus is believed to be an attractive inhibitory target for receptor molecular
      therapeutic. SU11274 was identified as a small molecule, ATP competitive
      inhibitor of the catalytic activity of the c-Met kinase. Our study had
      investigated the relationship between the high expression of c-Met and colorectal
      carcinoma and the effect of c-Met inhibitor SU11274 in colorectal carcinoma in
      vitro and vivo. Immunohistochemistry was used to detect the expression of c-Met
      in 60 patients with colorectal cancer and 20 patients with benign adenoma and
      surrounding normal colon tissues. The effect of SU11274 on human colorectal
      carcinoma LoVo cells was detected by Western blot and MTT. And the influence of
      SU11274 on cell cycle was determined by flow cytometry. In addition, LoVo cell
      transplanted tumor growth and expression of c-Met in nude mice was examined for
      inhibition of SU11274 in vivo. We found c-Met had high expression and was closely
      related to lymph node metastasis and TNM stage in colorectal carcinoma tissues.
      SU11274 significantly suppressed the phosphorylation of c-Met as well as the
      survival and proliferation of LoVo cell lines. G1-phase arrest was also induced
      by SU11274. SU11274 apparently restrained the growth of the xenograft tumor in
      nude mice. Our data suggest developing therapies that specifically inhibit the
      activation of c-Met may represent a novel therapeutic modality for patients with
      colorectal carcinoma expressing high levels of c-Met.

PMID- 23536001
TI  - The prognostic importance of changing serum M30 and M65 values after chemotherapy
      in patients with advanced-stage non-small-cell lung cancer.
AB  - Although oncological treatments are improving, the prognosis of non-small-cell
      lung cancer (NSCLC) patients has not. Several biomarkers related to prognosis
      have been evaluated, and M30 and M65 have been reported to be higher in patients
      with NSCLC than in healthy people. In the current study, we evaluated the
      clinical importance of the change in serum M30 and M65 values after chemotherapy
      in patients with NSCLC. Serum M30 and M65 values were measured before and 48 h
      after chemotherapy in thirty-two patients with advanced NSCLC. The importance of
      the change in the levels of these markers after chemotherapy was analyzed by
      univariate analysis. The median serum M65 and M30 values increased significantly
      after chemotherapy (p < 0.001). The median M30 value after chemotherapy was an
      important prognostic factor for both overall survival (OS) (p = 0.002) and
      progression-free survival (PFS) (p = 0.002). Stage and histopathological type
      were significant both for PFS and OS. Multivariate analysis showed that the
      median M30 value after chemotherapy was the only independent prognostic factor
      for PFS (p = 0.04, HR 5.4) and OS (p = 0.02, HR 11.49). Our results indicated
      that both serum M30 and M65 values increased after chemotherapy in patients with
      advanced NSCLC, and an elevated serum M30 value was an independent prognostic
      factor for both PFS and OS.

PMID- 23536003
TI  - Considering spatial ability in virtual route learning in early aging.
AB  - The aim of this study is to broaden our understanding of the construction and
      early decline of spatial mental representations in route learning, considering
      the extent to which spatial ability and age-related differences in environment
      learning interact. The experiment examines spatial mental representation derived
      from taking a realistic route acquired using virtual environment and compares
      individuals different in age but with similar spatial ability. A sample of 34
      young (20-30 years) and 30 middle-aged (50-60 years) females with good mental
      rotation ability were chosen. Participants learned a complex route through its
      presentation in a virtual environment and then performed a series of tasks
      (landmark recognition, location of landmarks and verification of spatial
      relations). Results show that the two participant age groups had similar
      performance in landmark recognition task and in verification of sentences
      describing direct spatial relations; instead, the middle-aged group showed a
      poorer performance than younger in their ability to locate landmarks and to judge
      the truth of indirect spatial sentences. These results first suggest that spatial
      abilities have to be seriously considered to avoid any confusion with age, as age
      related differences are attenuated when individuals are different in age but
      similar in spatial ability. Second they confirm a specific difficulty of older
      participants to handle spatial information in a global configuration. 

PMID- 23536004
TI  - Metal-free, highly efficient organocatalytic amination of benzylic C-H bonds.
AB  - A new synthetic approach toward direct C-N bond formation through sp(3) C-H
      activation has been developed under metal-free conditions. Both primary and
      secondary benzylic C-H substrates could react smoothly with various amines to
      give only mono-amination products with good to excellent yields.

PMID- 23536005
TI  - Synthetic transformations of a pendant nitrile moiety in group 4 metallocene
      complexes.
AB  - Functional group transformations at the group 4 metallocene framework have been
      demonstrated, which have provided relatively straightforward access to otherwise
      synthetically challenging derivatives. The pendant nitrile group in Ti and Zr
      metallocene complexes of the type [(eta(5)-C5Me5)(eta(5)-C5H4CMe2CH2CN)MCl2] was
      converted into an intramolecularly bound ketimido moiety by alkylation, which
      took place not only at the nitrile, but also at the metal centre. The choice of
      an alkylating reagent (alkyl/aryl lithium, Grignard reagent) was crucial: e.g., 2
      equiv. of MeMgBr effected the alkylation only at the metal, yielding selectively
      complexes [(eta(5)-C5Me5)(eta(5)-C5H4CMe2CH2CN)MMe2], while the use of PhMgBr,
      PhLi, or MeLi instead gave selectively the ketimido complexes. Organyl lithium
      reagents were, however, not compatible with the titanocene derivatives. The metal
      bound ketimides were subsequently cleaved off by the reaction with HCl, which
      afforded metallocene dichlorides with a pendant imino group. These compounds were
      easily protonated again at the nitrogen atom to produce a cationic iminium
      moiety. Aqueous hydrolysis of the imine or its respective hydrochloride proved to
      be viable in the case of Zr and it finally afforded a pendant ketone group
      attached to the zirconocene framework.

PMID- 23536002
TI  - Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of
      Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46.
AB  - The tumor suppressor protein Pdcd4 is a nuclear/cytoplasmic shuttling protein
      that has been implicated in the development of several types of human cancer. In
      the nucleus, Pdcd4 affects the transcription of specific genes by modulating the
      activity of several transcription factors. We have identified the Daxx protein as
      a novel interaction partner of Pdcd4. Daxx is a scaffold protein with roles in
      diverse processes, including transcriptional regulation, DNA-damage signaling,
      apoptosis and chromatin remodeling. We show that the interaction of both proteins
      is mediated by the N-terminal domain of Pdcd4 and the central part of Daxx, and
      that binding to Pdcd4 stimulates the degradation of Daxx, presumably by
      disrupting the interaction of Daxx with the de-ubiquitinylating enzyme Hausp.
      Daxx has previously been shown to serve as a scaffold for protein kinase Hipk2
      and tumor suppressor protein p53 and to stimulate the phosphorylation of p53 at
      serine 46 (Ser-46) in response to genotoxic stress. We show that Pdcd4 also
      disrupts the Daxx-Hipk2 interaction and inhibits the phosphorylation of p53. We
      also show that ultraviolet irradiation decreases the expression of Pdcd4. Taken
      together, our results support a model in which Pdcd4 serves to suppress the
      phosphorylation of p53 in the absence of DNA damage, while the suppressive effect
      of Pdcd4 is abrogated after DNA damage owing to the decrease of Pdcd4. Overall,
      our data demonstrate that Pdcd4 is a novel modulator of Daxx function and provide
      evidence for a role of Pdcd4 in restraining p53 activity in unstressed cells.

PMID- 23536006
TI  - A new site-specific recombinase-mediated system for targeted multiple genomic
      deletions employing chimeric loxP and mrpS sites.
AB  - A newly designed site-specific recombination system is presented which allows
      multiple targeted markerless deletions. The most frequently used tool for
      removing selection markers or to introduce genes by recombination-mediated
      cassette exchange is the Cre/loxP system. Many mutant loxP sites have been
      created for this purpose. However, this study presents a chimeric mutant loxP
      site denoted mroxP-site. The mroxP site consists of one Cre (loxP/2) and one MrpA
      (mrpS/2) binding site separated by a palindromic 6-bp spacer sequence. Two mroxP
      sites can be recombined by Cre recombinase in head-to-tail as well as in head-to
      head orientation. In the head-to-head orientation and the loxP half-sites inside,
      Cre removes the loxP half-sites during site-specific recombination, creating a
      new site, mrmrP. The new site is essentially a mrpS site with a palindromic
      spacer and cannot be used by Cre for recombination anymore. It does, however,
      present a substrate for the recombinase MrpA. This new system has been
      successfully applied introducing multiple targeted gene deletions into the
      Escherichia coli genome. Similar to Cre/loxP and FLP/FRT, this system may be
      adapted for genetic engineering of other pro- and eukaryotes. 

PMID- 23536007
TI  - Posterior interosseus nerve vs. medial cutaneous nerve of the forearm:
      differences in digital nerve reconstruction.
AB  - Digital nerve defects are common in hand trauma and for primary or secondary
      nerve reconstruction, the autologous nerve graft remains the gold standard. This
      study compares the regeneration results and donor side morbidity of either the
      posterior interosseus nerve (PIN) graft or the medial antebrachial cutaneous
      nerve (MACN) graft. 16 patients (group A, age 43 +/- 13 years) with digital nerve
      defects were treated with a PIN graft and 12 patients (group B, age 40 +/- 15
      years) received a MACN graft. The average nerve gap was 22 mm in each group.
      After a follow-up of 15 +/- 8 months in group A, S4-sensibility were measured in
      9 cases, S3+ in 5 cases and in 1 case S2 and S0. Up to an inconspicuously scar in
      projection of the fourth extensor-tendon compartment, there was no significant
      donor side morbidity. In group B, a S4-senibility has been obtained in 4 cases,
      S3+ in 5 cases, S3, S2 and S0 in each 1 case after a follow-up of 16 +/- 11
      months. Regarding the donor side morbidity, almost all patients complained about
      a disturbing scar formation and unpleasant paresthesia at the forearm down to the
      rascetta. Neuroma-associated pain has been detected in 4 cases. Although there
      has been no significant difference in terms of nerve regeneration, we recommend
      the use of the PIN graft for digital nerve reconstruction, since harvesting this
      nerve is fast and easy and without any donor side morbidity compared to the MACN
      graft.

PMID- 23536008
TI  - Quantitative detection of single base mutation by combining PNA hybridization and
      MALDI-TOF mass analysis.
AB  - Peptide nucleic acid (PNA) probes were designed to bind to the internal reference
      sequence and the single base mutation sequence within PCR-amplified DNA
      templates. PNAs hybridized to the target sequences on DNA were analyzed using
      MALDI-TOF mass spectrometry. Accurate quantification of the relative amount of
      mutant DNA was reproducibly demonstrated.

PMID- 23536010
TI  - Protein replacement therapies for rare diseases: a breeze for regulatory
      approval?
AB  - Protein replacement therapies for rare monogenic diseases have a higher
      probability of regulatory approval compared with biologics, small molecules, and
      grant-funded orphan drugs.

PMID- 23536011
TI  - Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of
      multiple types of cancer.
AB  - The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis
      in many solid tumors. Although there has long been interest in FGF pathway
      inhibitors, development has been complicated: An effective FGF inhibitor must
      block the activity of multiple mitogenic FGF ligands but must spare the metabolic
      hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To
      achieve these design requirements, we engineered a soluble FGF receptor 1 Fc
      fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF
      ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and
      vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and
      inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor
      response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c,
      and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1
      amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly
      sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind
      the hormonal FGFs, because these ligands require a cell surface co-receptor,
      klotho or beta-klotho, for high-affinity binding and signaling. Serum calcium and
      phosphate levels, which are regulated by FGF-23, are not altered by
      administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039
      treatment confers antitumor efficacy without the toxicities associated with other
      FGF pathway inhibitors.

PMID- 23536012
TI  - NETs are a source of citrullinated autoantigens and stimulate inflammatory
      responses in rheumatoid arthritis.
AB  - The early events leading to the development of rheumatoid arthritis (RA) remain
      unclear, but formation of autoantibodies to citrullinated protein antigens
      (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients
      with various autoimmune diseases display enhanced neutrophil extracellular trap
      (NET) formation, a phenomenon that exposes autoantigens in the context of
      immunostimulatory molecules. We investigated whether aberrant NETosis occurs in
      RA, determined its triggers, and examined its deleterious inflammatory
      consequences. Enhanced NETosis was observed in circulating and RA synovial fluid
      neutrophils compared to neutrophils from healthy controls and from patients with
      osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue,
      rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels
      and with systemic inflammatory markers. RA sera and immunoglobulin fractions from
      RA patients with high levels of ACPA and/or rheumatoid factor significantly
      enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct
      protein content. Indeed, during NETosis, neutrophils externalized the
      citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated
      vimentin antibodies potently induced NET formation. Moreover, the inflammatory
      cytokines interleukin-17A (IL-17A) and tumor necrosis factor-alpha (TNF-alpha)
      induced NETosis in RA neutrophils. In turn, NETs significantly augmented
      inflammatory responses in RA and OA synovial fibroblasts, including induction of
      IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate
      accelerated NETosis in RA pathogenesis, through externalization of citrullinated
      autoantigens and immunostimulatory molecules that may promote aberrant adaptive
      and innate immune responses in the joint and in the periphery, and perpetuate
      pathogenic mechanisms in this disease.

PMID- 23536014
TI  - Statistical challenges in the evaluation of treatments for small patient
      populations.
AB  - The development of a new treatment typically involves evaluation of its efficacy
      in a large clinical trial in which patients are randomly assigned either the new
      treatment or the standard of care. Results from these large randomized clinical
      trials allow for a definitive and unbiased assessment of the clinical benefit of
      the new treatment over the standard one. For rare diseases or for small patient
      subgroups identified within the context of a common disease, it may not be
      possible to conduct a large randomized trial. In this Review, we discuss
      alternative clinical study designs and statistical challenges that arise when
      attempting to assure that study results yield robust conclusions about the safety
      and effectiveness of a new medical product.

PMID- 23536013
TI  - Conserved shifts in the gut microbiota due to gastric bypass reduce host weight
      and adiposity.
AB  - Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity,
      and improved glucose metabolism. These effects are not simply attributable to
      decreased caloric intake or absorption, but the mechanisms linking rearrangement
      of the gastrointestinal tract to these metabolic outcomes are largely unknown.
      Studies in humans and rats have shown that RYGB restructures the gut microbiota,
      prompting the hypothesis that some of the effects of RYGB are caused by altered
      host-microbial interactions. To test this hypothesis, we used a mouse model of
      RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal
      RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham
      surgery, or sham surgery coupled to caloric restriction revealed that alterations
      to the gut microbiota after RYGB are conserved among humans, rats, and mice,
      resulting in a rapid and sustained increase in the relative abundance of
      Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These
      changes were independent of weight change and caloric restriction, were
      detectable throughout the length of the gastrointestinal tract, and were most
      evident in the distal gut, downstream of the surgical manipulation site. Transfer
      of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice
      resulted in weight loss and decreased fat mass in the recipient animals relative
      to recipients of microbiota induced by sham surgery, potentially due to altered
      microbial production of short-chain fatty acids. These findings provide the first
      empirical support for the claim that changes in the gut microbiota contribute to
      reduced host weight and adiposity after RYGB surgery.

PMID- 23536015
TI  - Elevated prefrontal myo-inositol and choline following breast cancer
      chemotherapy.
AB  - Breast cancer survivors are at increased risk for cognitive dysfunction, which
      reduces quality of life. Neuroimaging studies provide critical insights regarding
      the mechanisms underlying these cognitive deficits as well as potential biologic
      targets for interventions. We measured several metabolite concentrations using
      (1)H magnetic resonance spectroscopy as well as cognitive performance in 19
      female breast cancer survivors and 17 age-matched female controls. Women with
      breast cancer were all treated with chemotherapy. Results indicated significantly
      increased choline (Cho) and myo-inositol (mI) with correspondingly decreased N
      acetylaspartate (NAA)/Cho and NAA/mI ratios in the breast cancer group compared
      to controls. The breast cancer group reported reduced executive function and
      memory, and subjective memory ability was correlated with mI and Cho levels in
      both groups. These findings provide preliminary evidence of an altered metabolic
      profile that increases our understanding of neurobiologic status post-breast
      cancer and chemotherapy. 

PMID- 23536016
TI  - Prevalence and associations of potentially inappropriate prescriptions in
      Austrian nursing home residents: secondary analysis of a cross-sectional study.
AB  - BACKGROUND: Potentially inappropriate prescriptions (PIP) are an important cause
      of adverse medication-related events and increases morbidity, hospitalization,
      and health care costs, especially in nursing home residents. However, little is
      known about the associations between PIP and residents' characteristics.
      OBJECTIVE: The aim of our study was to analyse the prevalence and associations of
      PIP with residents' and facilities' characteristics. METHODS: We performed a
      secondary analysis of a cross-sectional study with 48 out of 50 eligible nursing
      homes and 1,844 out of 2,005 eligible residents in a defined rural-urban area in
      Austria. The Austrian list of potentially inappropriate medications was applied
      for the evaluation of inappropriate prescribing. Cluster-adjusted multiple
      regression analysis was used to investigate institutional and residents'
      characteristics associated with PIP. RESULTS: Mean cluster-adjusted prevalence of
      residents with at least one PIP was 70.3 % (95 % CI 67.2-73.4). The number of
      residents with at least one psychotropic PIP was 1.014 (55 %). The most often
      prescribed PIP were Prothipendyl (25.9 % residents), Lorazepam (14.5 %) and
      Diclofenac (6.1 %). Multiple regression analysis showed an inverse association of
      PIP with cognitive impairment and significant positive associations with
      permanent restlessness and permanent negative attitude. The associations of PIP
      with age and male gender were inconsistent. No significant associations were
      found for PIP and the ratio of staff nurses to residents. CONCLUSIONS: Our study
      results confirm that PIP is highly prevalent in the nursing home population.
      These results urgently call for effective interventions. Initiatives and
      successful interventions performed in other countries could serve as examples for
      safer prescribing in residents in Austria.

PMID- 23536017
TI  - Intravesical bacillus Calmette-Guerin instillation therapy for non-muscle
      invasive bladder cancer following solid organ transplantation.
AB  - BACKGROUND: Solid organ recipients have a substantial risk of developing bladder
      cancer, with high-risk non-muscle-invasive bladder cancer (NMIBC) being the most
      frequent diagnosis. Theoretically, adjuvant bacillus Calmette-Guerin (BCG)
      therapy is contraindicated, but limited data indicate its feasibility. The
      objective of this study was to evaluate the safety and efficacy of BCG following
      solid organ transplantation. MATERIALS AND METHODS: We reviewed the data of four
      solid organ recipients who received adjuvant BCG for high-risk NMIBC at our
      institution. Additionally, individual data of 12 patients were extracted from
      case series and case reports, which were identified through a systematic review
      of the literature. A meta-analysis was performed. RESULTS: Fourteen patients (88
      %) had received a kidney, one a heart, and one a liver transplant. The median
      time from transplantation to bladder cancer was 60.5 months. The regimen of
      immunosuppression was not modified in 12 patients (75 %). Forty-two percent of
      patients did not receive prophylactic antibiotics, and 70 % had no side effects.
      Ten patients (63 %) experienced recurrence after a median of 14 months.
      Progression to muscle-invasive or metastatic disease was observed in two patients
      (13 %). Four patients (25 %) underwent radical cystectomy, and two patients died
      of the disease. CONCLUSIONS: BCG therapy is a safe option for patients with high
      risk NMIBC following solid organ transplantation. However, there is a substantial
      risk of recurrence and progression. Urologists and patients considering BCG
      therapy should be aware of this and may consider early cystectomy. There is no
      evidence to support the need for prophylactic antibiotics.

PMID- 23536018
TI  - Experience with lenalidomide in an Austrian non-study population with advanced
      myelofibrosis.
AB  - Current literature provides conflicting evidence regarding the efficacy of
      lenalidomide in patients with myelofibrosis (MF). The aim of this work was to
      evaluate the efficacy of lenalidomide in patients with MF treated within a named
      patient program in Austria. A total of 22 patients with MF were treated with
      lenalidomide in 7 different centres throughout Austria. Median age of patients
      was 68 years. Primary MF was present in 13 patients. Eight patients had post
      polycythemia vera (post-PV) and 1 post-essential thrombocythemia (post-ET) MF.
      According to the Dynamic International Prognostic Scoring System (DIPSS), all
      patients were scored within the intermediate-2 or high-risk group. Approximately
      one-third of patients were treated with 2 or more prior therapies. The overall
      response rate according to International Working Group (IWG) criteria was 12.5 %.
      Efficacy of lenalidomide was moderate in this non-study patient population.
      Limiting factors seemed to be stage of disease and risk profile of patients
      included in this analysis.

PMID- 23536020
TI  - Annular dilatation and loss of sino-tubular junction in aneurysmatic aorta:
      implications on leaflet quality at the time of surgery. A finite element study.
AB  - OBJECTIVES: In the belief that stress is the main determinant of leaflet quality
      deterioration, we sought to evaluate the effect of annular and/or sino-tubular
      junction dilatation on leaflet stress. A finite element computer-assisted stress
      analysis was used to model four different anatomic conditions and analyse the
      consequent stress pattern on the aortic valve. METHODS: Theoretical models of
      four aortic root configurations (normal, with dilated annulus, with loss of sino
      tubular junction and with both dilatation simultaneously) were created with
      computer-aided design technique. The pattern of stress and strain was then
      analysed by means of finite elements analysis, when a uniform pressure of 100
      mmHg was applied to the model. Analysis produced von Mises charts (colour-coded,
      computational, three-dimensional stress-pattern graphics) and bidimensional plots
      of compared stress on arc-linear line, which allowed direct comparison of stress
      in the four different conditions. RESULTS: Stresses both on the free margin and
      on the 'belly' of the leaflet rose from 0.28 MPa (normal conditions) to 0.32 MPa
      (+14%) in case of isolated dilatation of the sino-tubular junction, while
      increased to 0.42 MPa (+67%) in case of isolated annular dilatation, with no
      substantial difference whether sino-tubular junction dilatation was present or
      not. CONCLUSIONS: Annular dilatation is the key element determining an increased
      stress on aortic leaflets independently from an associated sino-tubular junction
      dilatation. The presence of annular dilatation associated with root aneurysm
      greatly decreases the chance of performing a valve sparing procedure without the
      need for additional manoeuvres on leaflet tissue. This information may lead to a
      refinement in the optimal surgical strategy.

PMID- 23536021
TI  - Minimally invasive vacuum-assisted closure therapy in the management of complex
      pleural empyema.
AB  - OBJECTIVES: The pool of potential candidates for pleural empyema is expanding. In
      a previous technical report, we tested the feasibility of the minimally invasive
      insertion of a vacuum-assisted closure (Mini-VAC) system without the insertion of
      an open-window thoracostomy (OWT). In this study, we describe a consecutive case
      series of complex pleural empyemas that were managed by this Mini-VAC therapy.
      METHODS: In this retrospective study, we investigated 6 patients with
      multimorbidity (Karnofsky index <= 50%) who were consecutively treated with Mini
      VAC for a primary, postoperative or recurrent pleural empyema between January
      2011 and February 2012. RESULTS: Local control of the infection and control of
      sepsis were satisfactory in all 6 of the patients treated by Mini-VAC therapy.
      The suction used did not create any air leaks or bleeding from the lung or
      mediastinal structures. Mini-VAC therapy allowed a reduction of the empyema
      cavity and improved the re-expansion of the residual lung. Mini-VAC therapy
      resulted in a rapid eradication of the empyema. The chest wall was closed in all
      patients during the first hospital stay. All patients left the hospital in good
      health (Karnofsky index >70%) and with a non-infected pleural cavity at a mean of
      22 +/- 11 days after Mini-VAC installation. Pleural empyema was not detected in
      any of the 6 patients at the 3-month follow-up appointment. CONCLUSIONS: The Mini
      VAC procedure with the abdication of an OWT offers a rapid treatment for complex
      pleural empyema with minimal surgical effort and the opportunity for a primary
      closure of the empyema cavity.

PMID- 23536023
TI  - Structural diversity in iron oxide nanoparticle assemblies as directed by
      particle morphology and orientation.
AB  - The mesostructure of ordered arrays of anisotropic nanoparticles is controlled by
      a combination of packing constraints and interparticle interactions, two factors
      that are strongly dependent on the particle morphology. We have investigated how
      the degree of truncation of iron oxide nanocubes controls the mesostructure and
      particle orientation in drop cast mesocrystal arrays. The combination of grazing
      incidence small-angle X-ray scattering and scanning electron microscopy shows
      that mesocrystals of highly truncated cubic nanoparticles assemble in an fcc-type
      mesostructure, similar to arrays formed by iron oxide nanospheres, but with a
      significantly reduced packing density and displaying two different growth
      orientations. Strong satellite reflections in the GISAXS pattern indicate a
      commensurate mesoscopic superstructure that is related to stacking faults in
      mesocrystals of the anisotropic nanocubes. Our results show how subtle variation
      in shape anisotropy can induce oriented arrangements of nanoparticles of
      different structures and also create mesoscopic superstructures of larger
      periodicity.

PMID- 23536024
TI  - Recommended NICU design standards and the physical environment of the NICU.

PMID- 23536027
TI  - The design of neonatal incubators: a systems-oriented, human-centered approach.
AB  - OBJECTIVE: This report describes a multidisciplinary design project conducted in
      an academic setting reflecting a systems-oriented, human-centered philosophy in
      the design of neonatal incubator technologies. STUDY DESIGN: Graduate students in
      Architectural Design and Human Factors Engineering courses collaborated in a
      design effort that focused on supporting the needs of three user groups of
      incubator technologies: infant patients, family members and medical personnel.
      Design teams followed established human-centered design methods that included
      interacting with representatives from the user groups, analyzing sets of critical
      tasks and conducting usability studies with existing technologies. RESULT: An
      iterative design and evaluation process produced four conceptual designs of
      incubators and supporting equipment that better address specific needs of the
      user groups. CONCLUSION: This report introduces the human-centered design
      approach, highlights some of the analysis findings and design solutions, and
      offers a set of design recommendations for future incubation technologies.

PMID- 23536026
TI  - Recommended standards for newborn ICU design, eighth edition.
AB  - This is the eighth edition of the Recommended Standards for Newborn ICU Design.
      It contains substantive changes in recommendations for patient room size and
      feeding preparation areas, and a number of refinements of previous Recommended
      Standards with respect to family space, hand hygiene, lighting and other aspects
      of the newborn intensive care unit (NICU) design.

PMID- 23536025
TI  - Health consequences of shift work and implications for structural design.
AB  - The objective of the study was to perform a literature review on the health
      consequences of working rotating shifts and implications for structural design. A
      literature search was performed in June 2012 and a selection of the most relevant
      peer-review articles was included in the present review. Shift workers are more
      likely to suffer from a circadian sleep disorder characterized by sleepiness and
      insomnia. Shift work is associated with decreased productivity, impaired safety,
      diminished quality of life and adverse effects on health. Circadian disruption
      resulting from rotating shift work has also been associated with increased risk
      for metabolic syndrome, diabetes, cardiovascular disease and cancer. This article
      summarizes the known health effects of shift work and discusses how light can be
      used as a countermeasure to minimize circadian disruption at night while
      maintaining alertness. In the context of the lighted environment, implications
      for the design of newborn intensive care units are also discussed.

PMID- 23536022
TI  - Glutamate-dependent translational control in cultured Bergmann glia cells:
      eIF2alpha phosphorylation.
AB  - Glutamate (Glu), the major excitatory amino acid, activates a wide variety of
      signal transduction cascades. Synaptic plasticity relies on activity-dependent
      differential protein expression. Glu receptors have been critically involved in
      long-term synaptic changes, although recent findings suggest that Na(+)-dependent
      Glu transporters participate in Glu-induced signalling. Within the cerebellum,
      Bergmann glia cells are in close proximity to glutamatergic synapses and through
      their receptors and transporters, sense and respond to neuronal glutamatergic
      activity. Translational control represents the fine-tuning stage of protein
      expression regulation and Glu modulates this event in glial cells. In this
      context, we decided to explore the involvement of Glu receptors and transporters
      in the regulation of the initiation phase of protein synthesis. To this end,
      Bergmann glia cells were exposed to glutamatergic ligands and the serine 51
      phosphorylation pattern of the main regulator of the initiation phase of
      translation, namely the alpha subunit of eukaryotic initiation factor 2
      (eIF2alpha), determined. A time and dose-dependent increase in eIF2alpha
      phosphorylation was detected. The signalling cascade included Ca(2+) influx,
      activation of the Ca(2+)/calmodulin-dependent protein kinase II and protein
      kinase C. These results provide an insight into the molecular targets of the Glu
      effects at the translational level and strengthen the notion of the critical
      involvement of glia cells in glutamatergic synaptic function.

PMID- 23536029
TI  - Stochastic online appointment scheduling of multi-step sequential procedures in
      nuclear medicine.
AB  - The increased demand for medical diagnosis procedures has been recognized as one
      of the contributors to the rise of health care costs in the U.S. in the last few
      years. Nuclear medicine is a subspecialty of radiology that uses advanced
      technology and radiopharmaceuticals for the diagnosis and treatment of medical
      conditions. Procedures in nuclear medicine require the use of
      radiopharmaceuticals, are multi-step, and have to be performed under strict time
      window constraints. These characteristics make the scheduling of patients and
      resources in nuclear medicine challenging. In this work, we derive a stochastic
      online scheduling algorithm for patient and resource scheduling in nuclear
      medicine departments which take into account the time constraints imposed by the
      decay of the radiopharmaceuticals and the stochastic nature of the system when
      scheduling patients. We report on a computational study of the new methodology
      applied to a real clinic. We use both patient and clinic performance measures in
      our study. The results show that the new method schedules about 600 more patients
      per year on average than a scheduling policy that was used in practice by
      improving the way limited resources are managed at the clinic. The new
      methodology finds the best start time and resources to be used for each
      appointment. Furthermore, the new method decreases patient waiting time for an
      appointment by about two days on average. 

PMID- 23536030
TI  - [Organ toxicity of medicinal tumor therapy: morphological correlates].
AB  - CLINICAL/METHODOLOGICAL ISSUE: In antineoplastic chemotherapy classical
      cytostatic drugs are increasingly being supplemented by antibodies and so-called
      targeted therapies. In addition to the antineoplastic effect and general
      intolerance quite characteristic morphological changes can often be found and
      identified by the radiologist. The distinction between findings indicating side
      effects versus tumor progression or an infectious etiology is essential. FACTS
      AND CIRCUMSTANCES: Classical antineoplastic chemotherapy interacts with DNA and
      RNA synthesis, DNA repair or the mitosis process. In contrast modern targeted
      anticancer therapies act at the level of signal transduction pathways.Localized,
      organ-related changes are related to the metabolic characteristics of organs or
      anatomical features such as the properties of the local blood-tissue barrier.
      Toxicity associated findings often resemble fulminant tumor progression.
      EVALUATION: In new targeted anti-cancer therapies toxicity often occurs in a non
      cumulative way; therefore, morphological changes are often precursors of the
      manifestation of clinical toxicity. PRACTICAL RECOMMENDATIONS: Oncological
      radiology requires increasingly active interdisciplinary dialogue in order to
      delineate morphological correlates of organ toxicity against tumor progression
      and initiate appropriate therapeutic measures.

PMID- 23536031
TI  - [Imaging in oncology: terms and definitions].
AB  - Oncologic imaging includes the morphological description of the primary tumor
      region for an accurate classification of the tumor and lymph node stage and
      whether distant metastases have occurred according to the TNM staging system.
      Knowing the stage of the disease helps to plan the treatment and to estimate the
      prognosis. In clinical routine this is accomplished by conventional imaging
      techniques, such as ultrasound (US), computed tomography (CT) and magnetic
      resonance imaging (MRI). Additionally, oncologic imaging is essential in
      treatment monitoring to visualize and quantify the effect of cancer therapy
      according to response evaluation criteria in solid tumors (RECIST) and World
      Health Organization (WHO) criteria. The tremendous development in oncology and
      technical innovations in imaging represent a particular challenge for radiology.

PMID- 23536032
TI  - [Oncologic imaging: indications for and limitations of modern cross-sectional
      imaging techniques].
AB  - Cross-sectional imaging techniques, such as computed tomography (CT), magnetic
      resonance imaging (MRI), and positron emission tomography (PET) CT are an
      integral part of the modern oncological workup. They are used for tumor detection
      and staging as well as for treatment evaluation and monitoring. Due to
      pathophysiological and histological differences there is no universal imaging
      protocol for the assessment of different forms of cancer. For instance, CT is
      still the standard technique for the detection and staging of lung cancer
      supplemented by PET which aids the exclusion of nodal involvement and the
      detection of distant metastases. For hepatocellular carcinoma on the other hand,
      MRI is the preferred imaging technique, particularly when used in conjunction
      with liver-specific contrast media - PET/CT is only of limited value. Finally,
      for neuroendocrine tumors there is a focus on special radiotracers, which, in the
      context of PET/CT, enable a highly specific whole-body assessment. Thus,
      knowledge of the pathophysiological and imaging characteristics of different
      tumors is essential for a personalized, state-of-the art management of oncology
      patients.

PMID- 23536035
TI  - A universal flow cytometry assay for screening carbohydrate-active enzymes using
      glycan microspheres.
AB  - We describe a simple, multiplexed assay that integrates glycan synthesis,
      bioconjugation to microspheres, fluorescent chemical/biochemical detection and
      multiparameter flow cytometric analysis to screen activities of different
      families of carbohydrate-active enzymes.

PMID- 23536036
TI  - The long-lived electron transfer state of the 2-phenyl-4-(1-naphthyl)quinolinium
      ion incorporated into nanosized mesoporous silica-alumina acting as a robust
      photocatalyst in water.
AB  - A simple electron donor-acceptor linked dyad, the 2-phenyl-4-(1
      naphthyl)quinolinium ion (QuPh(+)-NA), was incorporated into nanosized mesoporous
      silica-alumina to form a composite, which is highly dispersed in water and acts
      as an efficient and robust photocatalyst for the reduction of O2 by oxalate to
      produce hydrogen peroxide with a quantum yield of 10%.

PMID- 23536037
TI  - Graphene-embedded 3D TiO2 inverse opal electrodes for highly efficient dye
      sensitized solar cells: morphological characteristics and photocurrent
      enhancement.
AB  - We demonstrated the preparation of graphene-embedded 3D inverse opal electrodes
      for use in DSSCs. The graphene was incorporated locally into the top layers of
      the inverse opal structures and was embedded into the TiO2 matrix via post
      treatment of the TiO2 precursors. DSSCs comprising the bare and 1-5 wt% graphene
      incorporated TiO2 inverse opal electrodes were compared. We observed that the
      local arrangement of graphene sheets effectively enhanced electron transport
      without significantly reducing light harvesting by the dye molecules. A high
      efficiency of 7.5% was achieved in DSSCs prepared with the 3 wt% graphene
      incorporated TiO2 inverse opal electrodes, constituting a 50% increase over the
      efficiencies of DSSCs prepared without graphene. The increase in efficiency was
      mainly attributed to an increase in J(SC), as determined by the photovoltaic
      parameters and the electrochemical impedance spectroscopy analysis.

PMID- 23536038
TI  - Comparison of radiation dose, workflow, patient comfort and financial break-even
      of standard digital radiography and a novel biplanar low-dose X-ray system for
      upright full-length lower limb and whole spine radiography.
AB  - OBJECTIVE: To compare the radiation dose, workflow, patient comfort, and
      financial break-even of a standard digital radiography and a biplanar low-dose X
      ray system. MATERIALS AND METHODS: A standard digital radiography system (Ysio,
      Siemens Healthcare, Erlangen, Germany) was compared with a biplanar X-ray unit
      (EOS, EOS imaging, Paris, France) consisting of two X-ray tubes and slot-scanning
      detectors, arranged at an angle of 90 degrees  allowing simultaneous vertical
      biplanar linear scanning in the upright patient position. We compared data of
      standing full-length lower limb radiographs and whole spine radiographs of both X
      ray systems. RESULTS: Dose-area product was significantly lower for radiographs
      of the biplanar X-ray system than for the standard digital radiography system
      (e.g. whole spine radiographs; standard digital radiography system: 392.2 +/-
      231.7 cGy*cm(2) versus biplanar X-ray system: 158.4 +/- 103.8 cGy*cm(2)). The
      mean examination time was significantly shorter for biplanar radiographs compared
      with standard digital radiographs (e.g. whole spine radiographs: 449 s vs 248 s).
      Patients' comfort regarding noise was significantly higher for the standard
      digital radiography system. The financial break-even point was 2,602
      radiographs/year for the standard digital radiography system compared with 4,077
      radiographs/year for the biplanar X-ray unit. CONCLUSION: The biplanar X-ray unit
      reduces radiation exposure and increases subjective noise exposure to patients.
      The biplanar X-ray unit demands a higher number of examinations per year for the
      financial break-even point, despite the lower labour cost per examination due to
      the shorter examination time.

PMID- 23536039
TI  - Skin rash during erlotinib for advanced non-small cell lung cancer: is age a
      clinical predictor?
AB  - The aim of this study was to evaluate the intensity and the duration of acneiform
      skin rash in young and elderly patients, to define a possible relationship
      between age and skin rash. We retrospectively analyzed all consecutive patients
      with advanced NSCLC who developed acneiform skin rash during erlotinib treatment
      at our Clinical Oncology Unit from June 2006 to May 2011. We divided the general
      case study into two subgroups: young and elderly patients (>= 65 years) and we
      compared clinical, pathological and therapeutical characteristics of both
      subgroups. Among 25 patients affected by advanced NSCLC treated with erlotinib
      during the reference period, 19 patients (76.0 %) developed acneiform skin rash.
      Fourteen (73.7 %) of 19 patients were elderly. The majority of elderly patients
      has developed acneiform skin rash (82.4 vs 62.5 %). In addition, in elderly
      patients, acneiform skin rash has a higher intensity (for mild rash 7.1 vs 20.0
      %, for moderate rash 57.1 vs 60.0 %, for severe rash 35.7 vs 20.0 %) and longer
      duration, especially for mild and moderate rash (for mild rash 154 vs 40 days,
      for moderate rash 120 vs 76 days, for severe rash 31 vs 85 days). The univariate
      analysis showed no statistical significant difference in OS between young and
      elderly patients (p = 0.191), such as age, does not seem to influence the
      appearance (p = 0.386), duration (p = 0.455) and grade of acneiform skin rash (p
      = 0.765). In conclusion, we can affirm that age is an insufficient predictor of
      acneiform skin rash during erlotinib treatment in advanced NSCLC and does not
      seem to statistically influence the appearance, duration and grade of skin rash.

PMID- 23536040
TI  - Expression profile and mitochondrial colocalization of Tdp1 in peripheral human
      tissues.
AB  - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that processes
      blocked 3' ends of DNA breaks. Functional loss of Tdp1 causes spinocerebellar
      ataxia with axonal neuropathy type 1 (SCAN1). Based on the prominent cytoplasmic
      expression of Tdp1 in the neurons presumably affected in SCAN1, we hypothesized
      that Tdp1 participates in the repair of mitochondrial DNA. As a step toward
      testing this hypothesis, we profiled Tdp1 expression in different human tissues
      by immunohistochemistry and immunofluorescence respectively and determined
      whether Tdp1 was expressed in the cytoplasm of tissues other than the neurons. We
      found that Tdp1 was ubiquitously expressed and present in the cytoplasm of many
      cell types. Within human skeletal muscle and multiple mouse tissues, Tdp1
      partially colocalized with the mitochondria. In cultured human dermal
      fibroblasts, Tdp1 redistributed to the cytoplasm and partially colocalized with
      mitochondria following oxidative stress. These studies suggest that one role of
      cytoplasmic Tdp1 is the repair of mitochondrial DNA lesions arising from
      oxidative stress. 

PMID- 23536041
TI  - Spindle cell carcinomas of the head and neck rarely harbor transcriptionally
      active human papillomavirus.
AB  - Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma
      characterized by spindled or pleomorphic cells which appear to be a true sarcoma
      but are actually epithelial. Some head and neck squamous cell carcinoma variants
      can be human papillomavirus (HPV)-related and have improved outcomes. We sought
      to determine if spindle cell carcinomas are associated with transcriptionally
      active HPV. Cases of spindle cell carcinoma were retrieved from department files.
      Transcriptionally-active HPV was determined by mRNA in situ hybridization for
      high risk HPV E6 and E7 transcripts and by a surrogate marker, p16
      immunohistochemistry, with a 50% staining cutoff. RT-PCR for high risk HPV mRNA
      was performed on the cases that were technical failures by in situ hybridization.
      Medical records and follow up information were retrieved for all patients. Of 31
      cases, 5 were from the oropharynx, 12 from the oral cavity, and 14 from the
      larynx or hypopharynx. One purely spindled oral cavity spindle cell carcinoma was
      HPV positive. It was also diffusely positive for p16. Another laryngeal spindle
      cell carcinoma was HPV positive in both the squamous and spindle cell components,
      but was negative for p16. None of the five oropharyngeal spindle cell carcinomas
      were positive for p16 or HPV RNA. The HPV positive patients both presented at
      high stage (IV) and died with disease within 2 years of diagnosis. The majority
      of spindle cell carcinomas of the head and neck, including those arising in the
      oropharynx, are not related to transcriptionally active HPV. Although the number
      of cases is too small for any definitive conclusions, for the rare HPV positive
      spindle cell carcinoma cases, positive viral status does not appear to confer any
      prognostic benefit.

PMID- 23536043
TI  - Three new three-dimensional organic-inorganic hybrid compounds based on
      PMo12O40(n-) (n = 3 or 4) polyanions and Cu(I)-pyrazine/Cu(I)-pyrazine-Cl porous
      coordination polymers.
AB  - Three new organic-inorganic hybrid compounds based on PMo12O40(n-) (n = 3 or 4)
      polyanions and Cu(I)-pz/Cu(I)-pz-Cl porous coordination polymers:
      [Cu(I)(pz)]3[PMo(VI)12O40] (1), [Cu(I)(pz)1.5]4[PMo(V)Mo(VI)11O40].pz.2H2O (2),
      [Cu(I)3(pz)3Cl][Cu(I)2(pz)3(H2O)][PMo(V)Mo(VI)11O40] (3) (pz = pyrazine) have
      been hydrothermally prepared and characterized by elemental analysis, IR, TG,
      XRD, XPS and single-crystal X-ray diffraction. Compound 1 presents a three
      dimensional Cu(I)-pz framework with cube-like chambers, into which PMo(VI)12O40(3
      ) Keggin ions are incorporated. Compound 2 shows a three-dimensional sandwich
      like framework, and PMo(V)Mo(VI)11O40(4-) polyanions are located in the octagonal
      voids of every two-dimensional Cu(I)-pz 4(1)8(2) network structure. Compound 3
      exhibits a two-dimensional Cl-bridged Cu(I)-pz-Cl double-layer structure, and two
      kinds of PMo(V)Mo(VI)11O40(4-) polyanions as bridging linkers connect two
      adjacent double-layers to form a three-dimensional organic-inorganic framework
      through Cu(I)-O bonds. Additionally, their electrochemical characters,
      electrocatalytic behaviors and solid state fluorescent properties at room
      temperature have been investigated in detail.

PMID- 23536042
TI  - "Banded bypass": the way to go?

PMID- 23536044
TI  - Use of baclofen for withdrawal in a preterm infant.
AB  - Baclofen is a gamma-aminobutyric acid agonist used primarily as a muscle relaxant
      to treat spasticity in children and adults. Withdrawal of oral baclofen is known
      to cause a withdrawal syndrome in adults. Only one previous case describes a
      withdrawal syndrome in a term infant, manifested by seizures, associated with the
      use of oral baclofen in the mother. This case describes a withdrawal syndrome and
      the unique use of baclofen for withdrawal in a preterm infant.

PMID- 23536045
TI  - Intravitreal ganciclovir for neonatal cytomegalovirus-associated retinitis: a
      case report.
AB  - Congenital cytomegalovirus (CMV) infection is a major cause of birth defects and
      childhood disorders in the United States. Retinitis occurs in 25% of infants with
      severely symptomatic congenital CMV and in ~1% of asymptomatic infants.
      Intravitreal ganciclovir is recommended in adults with CMV retinitis (CMVR)
      refractory or noncompliant to intravenous therapy. No literature is available
      discussing the use of intravitreal ganciclovir for CMVR in neonates. We report a
      term neonate who received intravenous and intravitreal ganciclovir for treatment
      of CMVR. Three doses of intravitreal ganciclovir (2 mg per dose in each eye) were
      administered. Intravitreal injections of ganciclovir appeared to be well
      tolerated and improvement of the retinitis was appreciated. Intravitreal
      ganciclovir is an effective treatment of CMVR in adult acquired immunodeficiency
      syndrome (AIDS) patients. We report one case of intravitreal ganciclovir in a
      term neonate with promising results.

PMID- 23536046
TI  - Potassium ions are more effective than sodium ions in salt induced peptide
      formation.
AB  - Prebiotic peptide formation under aqueous conditions in the presence of metal
      ions is one of the plausible triggers of the emergence of life. The salt-induced
      peptide formation reaction has been suggested as being prebiotically relevant and
      was examined for the formation of peptides in NaCl solutions. In previous work we
      have argued that the first protocell could have emerged in KCl solution. Using
      HPLC-MS/MS analysis, we found that K(+) is more than an order of magnitude more
      effective in the L-glutamic acid oligomerization with 1,1'-carbonyldiimidazole in
      aqueous solutions than the same concentration of Na(+), which is consistent with
      the diffusion theory calculations. We anticipate that prebiotic peptides could
      have formed with K(+) as the driving force, not Na(+), as commonly believed.

PMID- 23536047
TI  - Degradation of glycine and alanine on irradiated quartz.
AB  - Recent researches suggest participation of minerals in the formation of life
      under primordial conditions. Among all of the minerals, quartz seems to be one of
      the most probable to take part in such processes. However, an external source of
      energy is needed, e.g. electric discharge. A device simulating the proposed
      conditions was designed and was used to simulate prebiotic conditions.
      Investigation of processes occurring during the stimulation of quartz with
      electric discharge was studied by means of Ultraviolet-visible (UV-VIS)
      spectroscopy, in order to monitor the generation kinetics of free radicals.
      Additionally, infrared spectroscopy was applied to identify chemical reaction
      products created in a solution of alanine or glycine, in the presence of quartz
      treated with electric discharge. Formation of increased amounts of free radicals,
      compared to experiments performed without quartz and/or amino acid, is reported,
      along with identification of possible degradation products of alanine. No
      synthetic reactions were observed.

PMID- 23536048
TI  - Stripe rust resistance genes in the UK winter wheat cultivar Claire.
AB  - Stripe rust resistance in the winter wheat cultivar Claire had remained effective
      in the UK and Europe since its release in 1999 and consequently has been used
      extensively in wheat breeding programs. However, in 2012, reports indicated that
      this valuable resistance may now have been compromised. To characterise stripe
      rust resistance in Claire and determine which genes may still confer effective
      resistance a cross was made between Claire and the stripe rust susceptible
      cultivar Lemhi. A genetic linkage map, constructed using SSR, AFLP, DArT and NBS
      AFLP markers had a total map length of 1,730 cM. To improve the definition of two
      quantitative trait loci (QTL) identified on the long arm of chromosome 2D further
      markers were developed from wheat EST. Stripe rust resistance was evaluated on
      adult plants under field and glasshouse conditions by measuring the extent of
      fungal growth and sporulation, percentage infection (Pi) and the
      necrotic/chlorotic responses of the plant to infection, infection type (IT). Four
      QTL contributing to stripe rust adult plant resistance (APR) were identified in
      Claire, QYr.niab-2D.1, QYr.niab-2D.2, QYr.niab-2B and QYr.niab-7B. For Pi
      QYr.niab-2D.1 explained up to 25.4 % of the phenotypic variation, QYr.niab-2D.2
      up to 28.7 %, QYr.niab-2B up to 21.7 % and QYr.niab-7B up to 13.0 %. For IT the
      percentages of phenotypic variation explained were 23.4, 31.8, 17.2 and 12.6 %,
      respectively. In addition to the four QTL conferring APR in Claire, a race
      specific, seedling expressed resistance gene was identified on chromosome 3B.

PMID- 23536049
TI  - Genetic control of soybean seed oil: II. QTL and genes that increase oil
      concentration without decreasing protein or with increased seed yield.
AB  - Soybean [Glycine max (L.) Merrill] seed oil is the primary global source of
      edible oil and a major renewable and sustainable feedstock for biodiesel
      production. Therefore, increasing the relative oil concentration in soybean is
      desirable; however, that goal is complex due to the quantitative nature of the
      oil concentration trait and possible effects on major agronomic traits such as
      seed yield or protein concentration. The objectives of the present study were to
      study the relationship between seed oil concentration and important agronomic and
      seed quality traits, including seed yield, 100-seed weight, protein
      concentration, plant height, and days to maturity, and to identify oil
      quantitative trait loci (QTL) that are co-localized with the traits evaluated. A
      population of 203 F4:6 recombinant inbred lines, derived from a cross between
      moderately high oil soybean genotypes OAC Wallace and OAC Glencoe, was developed
      and grown across multiple environments in Ontario, Canada, in 2009 and 2010.
      Among the 11 QTL associated with seed oil concentration in the population, which
      were detected using either single-factor ANOVA or multiple QTL mapping methods,
      the number of QTL that were co-localized with other important traits QTL were six
      for protein concentration, four for seed yield, two for 100-seed weight, one for
      days to maturity, and one for plant height. The oil-beneficial allele of the QTL
      tagged by marker Sat_020 was positively associated with seed protein
      concentration. The oil favorable alleles of markers Satt001 and GmDGAT2B were
      positively correlated with seed yield. In addition, significant two-way epistatic
      interactions, where one of the interacting markers was solely associated with
      seed oil concentration, were identified for the selected traits in this study.
      The number of significant epistatic interactions was seven for yield, four for
      days to maturity, two for 100-seed weight, one for protein concentration, and one
      for plant height. The identified molecular markers associated with oil-related
      QTL in this study, which also have positive effects on other important traits
      such as seed yield and protein concentration, could be used in the soybean marker
      breeding programs aimed at developing either higher seed yield and oil
      concentration or higher seed protein and oil concentration per hectare.
      Alternatively, selecting complementary parents with greater breeding values due
      to positive epistatic interactions could lead to the development of higher oil
      soybean cultivars.

PMID- 23536050
TI  - Targeting polymeric fluorescent nanodiamond-gold/silver multi-functional
      nanoparticles as a light-transforming hyperthermia reagent for cancer cells.
AB  - This work demonstrates a simple route for synthesizing multi-functional
      fluorescent nanodiamond-gold/silver nanoparticles. The fluorescent nanodiamond is
      formed by the surface passivation of poly(ethylene glycol) bis(3-aminopropyl)
      terminated. Urchin-like gold/silver nanoparticles can be obtained via one-pot
      synthesis, and combined with each other via further thiolation of nanodiamond.
      The morphology of the nanodiamond-gold/silver nanoparticles thus formed was
      identified herein by high-resolution transmission electron microscopy, and
      clarified using diffraction patterns. Fourier transform infrared spectroscopy
      clearly revealed the surface functionalization of the nanoparticles. The
      fluorescence of the materials with high photo stability was examined by high
      power laser irradiation and long-term storage at room temperature. To develop the
      bio-recognition of fluorescent nanodiamond-gold/silver nanoparticles, pre
      modified transferrin was conjugated with the gold/silver nanoparticles, and the
      specificity and activity were confirmed in vitro using human hepatoma cell line
      (J5). The cellular uptake analysis that was conducted using flow cytometry and
      inductively coupled plasma mass spectrometry exhibited that twice as many
      transferrin-modified nanoparticles as bare nanoparticles were engulfed, revealing
      the targeting and ease of internalization of the human hepatoma cell.
      Additionally, the in situ monitoring of photothermal therapeutic behavior reveals
      that the nanodiamond-gold/silver nanoparticles conjugated with transferrin was
      more therapeutic than the bare nanodiamond-gold/silver materials, even when
      exposed to a less energetic laser source. Ultimately, this multi-functional
      material has great potential for application in simple synthesis. It is non
      cytotoxic, supports long-term tracing and can be used in highly efficient
      photothermal therapy against cancer cells.

PMID- 23536051
TI  - The results of closing wedge osteotomy with posterior instrumented fusion for the
      surgical treatment of congenital kyphosis.
AB  - PURPOSE: There exist not much data regarding the surgical treatment of pure
      congenital kyphosis (CK) in the literature. The purpose of this study was to
      evaluate the results of closing wedge osteotomy with posterior instrumented
      fusion in patients with congenital kyphotic deformity. METHODS: We
      retrospectively evaluated the radiographical results of 10 patients who were
      subject to closing wedge vertebral osteotomy and posterior instrumented fusion
      due to CK. The mean age of the patients at surgery was 12.6 +/- 3.72 years (range
      8-18 years). Radiographical measurements including local kyphosis, correction
      loss, global kyphosis and sagittal balance values were noted for the
      preoperative, postoperative and final follow up periods, respectively. The data
      obtained from those periods underwent statistical analysis. RESULTS: Average
      follow-up period was 51.8 +/- 29.32 months (range 26-96 months). The mean local
      kyphosis angle was 67.7 degrees  +/- 15.64 degrees  (range 42 degrees -88 degrees
      ) prior to the surgery, 31.5 degrees  +/- 17.12 (range 14 degrees -73 degrees )
      following the surgery and 31.9 degrees  +/- 15.98 degrees  (range 14 degrees -71
      degrees ) during the follow up-period, respectively (p < 0.05). A correction rate
      of 53.5 % was reported at the final follow up. Average sagittal balance was
      measured as 33.1 +/- 24.48 mm (range 2-77 mm) prior to the surgery, 20.8 +/-
      15.46 mm (range 5-46 mm) following the surgery (p < 0.05) and 14.1 +/- 9.2 mm
      (range 0-30 mm) during follow-up period (p > 0.05). Complications consisted of a
      rod fracture due to pseudoarthrosis, an implant failure with loosening of screws
      and a proximal junctional kyphosis. No neurological deficit or deep infection
      were encountered in any of the patients in the study group. CONCLUSION: Closing
      wedge osteotomy with posterior instrumented fusion is an efficient method of
      surgical treatment in terms of sagittal balance restoration and deformity
      correction in patients with congenital kyphosis.

PMID- 23536052
TI  - Long-term results of rectal cancer surgery with a systematical operative
      approach.
AB  - BACKGROUND: Variabilities of both oncologic and functional outcomes are major
      problems after rectal cancer treatment. Standardized techniques might produce
      more consistent surgical quality. This study reports outcomes during a 20-year
      period resulting from a systematically applied surgical approach. METHODS:
      Between 1990 and 2010, 368 rectal cancer patients, treated with total mesorectal
      excision conducted in a standardized, stepwise approach, were prospectively
      entered into a database. Influence of time period, surgeon, tumor and anastomotic
      height, and resection type was evaluated with multivariable regression analyses
      adjusting for age, disease stage, diversion, and (neo)adjuvant treatment.
      Function outcome questionnaires were sent to 50 patients at least 5 years after
      surgery. RESULTS: Five-year overall survival was 76.4 %. Local and distant
      recurrence rates were 5.2 % and 22.1 %. Anastomotic leakage occurred in 5.4 % of
      patients treated with low anterior resection (n = 259). Time period, surgeon,
      tumor and anastomotic height, diversion, and abdominoperineal resection were not
      independent risk factors for any of these outcome measures. Both preoperative and
      postoperative radiotherapy were independently associated with increased risk of
      metastases (P = 0.035, hazard ratio (HR) = 3.04; and P = 0.029, HR = 3.59).
      Function questionnaires were completed by 38 of 50 patients (76 %). One of 13
      nonirradiated patients reported mild fecal incontinence compared with 20 of 25
      irradiated patients reporting mostly moderate-severe incontinence (P < 0.001).
      CONCLUSIONS: Systematically applied surgical dissection results consistently in
      excellent oncologic outcomes with enhanced function outcomes. The findings
      suggest that in the presence of highly disciplined surgery, radiotherapy might
      make a smaller contribution to oncologic outcome, while leading to serious
      adverse effects.

PMID- 23536053
TI  - The prognostic value of lymph node ratio in node-positive breast cancer: a Dutch
      nationwide population-based study.
AB  - BACKGROUND: The absolute number of involved axillary lymph nodes (LNs) is
      considered the most important prognostic factor in breast cancer. Over the last
      decade, several studies indicated that the lymph node ratio (LNR) might predict
      outcome better than the number of positive LNs. In this study we test the
      applicability of earlier published LNR cutoff values and study the prognostic
      value of the LNR on a nationwide level. METHODS: A nationwide population-based
      study was performed, using data from the Netherlands Cancer Registry, including
      all women diagnosed with node-positive breast cancer between 1999 and 2005 (N =
      25,315). Patients were divided into 3 LNR risk groups (low, <=0.20; intermediate,
      0.21-0.65; and high, >0.65). Kaplan-Meier survival analysis was performed. In
      order to evaluate whether LNR was associated with overall survival (OS), Cox
      proportional hazards modeling was used. RESULTS: For the entire cohort, 5- and 10
      year OS rates were 78 % and 62 %, respectively. The number of positive LNs
      correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1-3, 4-9,
      and 10 or more positive LNs, respectively, P < .001). LNR also correlated with OS
      (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups,
      respectively, P < .001). In the multivariable analysis, the risk of death
      increased with increasing LNR (P < .001). CONCLUSIONS: The LNR has an important
      prognostic value in node-positive patients, independent of traditional
      clinicopathological factors. LNR should be added as an independent prognostic
      variable to the current staging system.

PMID- 23536055
TI  - A novel approach to fingerprint visualization on paper using nanotechnology:
      reversing the appearance by tailoring the gold nanoparticles' capping ligands.
AB  - Gold nanoparticles, AuNPs, capped with mercaptocarboxylic acids followed by
      silver precipitation develop latent fingermarks on paper as high quality
      "negative" impressions. This effect stems from hydrogen bonding between the
      carboxylic group and the paper cellulose and may improve the yield of latent
      fingermarks since the results are less dependent on sweat composition.

PMID- 23536054
TI  - Association of positive transection margins with gastric cancer survival and
      local recurrence.
AB  - PURPOSE: To examine the association between positive resection margins and
      survival and local recurrence in patients with gastric cancer undergoing
      resection with curative intent. METHODS: Patients who underwent curative intent
      resection for gastric carcinoma from 1985 to 2010 were identified from a
      prospectively maintained database. Positive margins were defined as disease
      present at the line of luminal transection. Clinicopathological features and
      outcome of patients undergoing gastrectomy with negative and positive margins
      were compared. RESULTS: Among 2384 patients undergoing curative intent resection,
      108 (4.5 %) had positive margins. Positive margins were associated with higher
      American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number
      of positive nodes, diffuse Lauren type, and poorly differentiated tumors.
      Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy
      (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and
      unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin
      status, T stage, N stage, grade, and perineural invasion to be independent
      predictors of survival. Margin status was an independent predictor of survival in
      patients with <=3 positive nodes or T1-2 disease but was not in patients with >3
      positive nodes or T3-4 disease. Local recurrence occurred in 16 % of patients
      with a positive margin. We identified no factors predictive of local recurrence
      in patients with positive margins. CONCLUSIONS: Positive resection margin is
      associated with advanced AJCC stage and aggressive tumor biology but remains an
      independent predictor of worse survival. The significance of a positive margin in
      gastric cancer is confined to patients with nontransmural disease and/or limited
      nodal involvement.

PMID- 23536056
TI  - A multicenter study for a single, three-step laser treatment for cellulite using
      a 1440-nm Nd:YAG laser, a novel side-firing fiber, and a temperature-sensing
      cannula.
AB  - BACKGROUND: Historically, treatments for cellulite have not been able to address
      all of its physiological components and require multiple sessions. OBJECTIVE: The
      authors evaluate the safety and efficacy of a single, subdermal procedure to
      treat the underlying structure of cellulite. METHODS: Fifty-seven patients
      underwent a 3-step cellulite treatment with a 1440-nm Nd:YAG laser with a side
      firing fiber and temperature-sensing cannula. Efficacy was measured by the
      ability of blinded evaluators to distinguish baseline photos from those taken at
      3 and 6 months posttreatment, as well as their rating of the results on a 5
      point, 2-category ordinal photonumeric scale when comparing baseline photos to
      those taken at 2, 3, and 6 months posttreatment. Patient and physician
      satisfaction was assessed based on completion of a satisfaction survey at 2, 3,
      and 6 months posttreatment. Adverse events (AE) were recorded throughout the
      study. RESULTS: At 6 months posttreatment, blinded evaluators rated at least a 1
      point improvement in the appearance of cellulite in 96% of treated sites. Blinded
      evaluators were also able to correctly identify baseline versus posttreatment
      photos in 95% of cases. At least 90% of patients and physicians reported
      satisfaction with the results of treatment throughout 6 months. AE were mild in
      intensity and transient to treatment. CONCLUSIONS: A single, 3-step, minimally
      invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and
      temperature-sensing cannula to treat the underlying structure of cellulite proved
      to be safe and maintained effectiveness at least 6 months posttreatment. LEVEL OF
      EVIDENCE: 2.

PMID- 23536057
TI  - Compact high power barium nitrite crystal-based Raman laser at 1197 nm for
      photoacoustic imaging of fat.
AB  - Photoacoustic imaging employing molecular overtone vibration as a contrast
      mechanism opens a new avenue for bond-selective imaging of deep tissues. Broad
      use of this modality is, however, hampered by the extremely low conversion
      efficiency of optical parametric oscillators at the overtone transition
      wavelengths. To overcome such a barrier, we demonstrate the construction and use
      of a compact, barium nitrite crystal-based Raman laser for photoacoustic imaging
      of C-H overtone vibrations. Using a 5-ns Nd?YAG laser as the pumping source, up
      to 21.4 mJ pulse energy at 1197 nm was generated, corresponding to a conversion
      efficiency of 34.8%. Using the 1197 nm pulses, three-dimensional photoacoustic
      imaging of intramuscular fat was demonstrated.

PMID- 23536058
TI  - Autobiographical memory transformation across consolidation.

PMID- 23536059
TI  - Endocannabinoid signaling alters internal programming of neuronal fate
      specification.

PMID- 23536060
TI  - Parsing the phonological loop: activation timing in the dorsal speech stream
      determines accuracy in speech reproduction.
AB  - Despite significant research and important clinical correlates, direct neural
      evidence for a phonological loop linking speech perception, short-term memory and
      production remains elusive. To investigate these processes, we acquired whole
      head magnetoencephalographic (MEG) recordings from human subjects performing a
      variable-length syllable sequence reproduction task. The MEG sensor data were
      source localized using a time-frequency optimized spatially adaptive filter, and
      we examined the time courses of cortical oscillatory power and the correlations
      of oscillatory power with behavior between onset of the audio stimulus and the
      overt speech response. We found dissociations between time courses of
      behaviorally relevant activations in a network of regions falling primarily
      within the dorsal speech stream. In particular, verbal working memory load
      modulated high gamma power in both Sylvian-parietal-temporal and Broca's areas.
      The time courses of the correlations between high gamma power and subject
      performance clearly alternated between these two regions throughout the task. Our
      results provide the first evidence of a reverberating input-output buffer system
      in the dorsal stream underlying speech sensorimotor integration, consistent with
      recent phonological loop, competitive queuing, and speech-motor control models.
      These findings also shed new light on potential sources of speech dysfunction in
      aphasia and neuropsychiatric disorders, identifying anatomically and behaviorally
      dissociable activation time windows critical for successful speech reproduction.

PMID- 23536061
TI  - Role of inhibition in respiratory pattern generation.
AB  - Postsynaptic inhibition is a key element of neural circuits underlying behavior,
      with 20-50% of all mammalian (nongranule) neurons considered inhibitory. For
      rhythmic movements in mammals, e.g., walking, swimming, suckling, chewing, and
      breathing, inhibition is often hypothesized to play an essential rhythmogenic
      role. Here we study the role of fast synaptic inhibitory neurotransmission in the
      generation of breathing pattern by blocking GABA(A) and glycine receptors in the
      preBotzinger complex (preBotC), a site essential for generation of normal
      breathing pattern, and in the neighboring Botzinger complex (BotC). The breathing
      rhythm continued following this blockade, but the lung inflation-induced Breuer
      Hering inspiratory inhibitory reflex was suppressed. The antagonists were
      efficacious, as this blockade abolished the profound effects of the exogenously
      applied GABA(A) receptor agonist muscimol or glycine, either of which under
      control conditions stopped breathing in vagus-intact or vagotomized,
      anesthetized, spontaneously breathing adult rats. In vagotomized rats,
      GABA(A)ergic and glycinergic antagonists had little, if any, effect on rhythm.
      The effect in vagus-intact rats was to slow the rhythm to a pace equivalent to
      that seen after suppression of the aforementioned Breuer-Hering inflation reflex.
      We conclude that postsynaptic inhibition within the preBotC and BotC is not
      essential for generation of normal respiratory rhythm in intact mammals. We
      suggest the primary role of inhibition is in shaping the pattern of respiratory
      motor output, assuring its stability, and in mediating reflex or volitional
      apnea, but not in the generation of rhythm per se.

PMID- 23536062
TI  - Global similarity and pattern separation in the human medial temporal lobe
      predict subsequent memory.
AB  - Intense debate surrounds the role of medial temporal lobe (MTL) structures in
      recognition memory. Using high-resolution fMRI and analyses of pattern similarity
      in humans, we examined the encoding computations subserved by MTL subregions.
      Specifically, we tested the theory that MTL cortex supports memory by encoding
      overlapping representations, whereas hippocampus supports memory by encoding
      pattern-separated representations. Consistent with this view, the relationship
      between encoding pattern similarity and subsequent memory dissociated MTL cortex
      and hippocampus: later memory was predicted by greater across-item pattern
      similarity in perirhinal cortex and in parahippocampal cortex, but greater
      pattern distinctiveness in hippocampus. Additionally, by comparing neural
      patterns elicited by individual stimuli regardless of subsequent memory, we found
      that perirhinal cortex and parahippocampal cortex exhibited differential content
      sensitivity for multiple stimulus categories, whereas hippocampus failed to
      demonstrate content sensitivity. These data provide novel evidence that
      complementary MTL encoding computations subserve declarative memory.

PMID- 23536063
TI  - Inhibitory interneurons decorrelate excitatory cells to drive sparse code
      formation in a spiking model of V1.
AB  - Sparse coding models of natural scenes can account for several physiological
      properties of primary visual cortex (V1), including the shapes of simple cell
      receptive fields (RFs) and the highly kurtotic firing rates of V1 neurons.
      Current spiking network models of pattern learning and sparse coding require
      direct inhibitory connections between the excitatory simple cells, in conflict
      with the physiological distinction between excitatory (glutamatergic) and
      inhibitory (GABAergic) neurons (Dale's Law). At the same time, the computational
      role of inhibitory neurons in cortical microcircuit function has yet to be fully
      explained. Here we show that adding a separate population of inhibitory neurons
      to a spiking model of V1 provides conformance to Dale's Law, proposes a
      computational role for at least one class of interneurons, and accounts for
      certain observed physiological properties in V1. When trained on natural images,
      this excitatory-inhibitory spiking circuit learns a sparse code with Gabor-like
      RFs as found in V1 using only local synaptic plasticity rules. The inhibitory
      neurons enable sparse code formation by suppressing predictable spikes, which
      actively decorrelates the excitatory population. The model predicts that only a
      small number of inhibitory cells is required relative to excitatory cells and
      that excitatory and inhibitory input should be correlated, in agreement with
      experimental findings in visual cortex. We also introduce a novel local learning
      rule that measures stimulus-dependent correlations between neurons to support
      "explaining away" mechanisms in neural coding.

PMID- 23536064
TI  - Novel GABAergic circuits mediating excitation/inhibition of Cajal-Retzius cells
      in the developing hippocampus.
AB  - Cajal-Retzius cells are a class of neurons believed to play critical roles during
      cortical development. However, their network computational functions remain
      poorly understood. Although work in the neocortex and hippocampus has shown that
      Cajal-Retzius cells receive predominantly, if not exclusively, spontaneous
      GABA(A) receptor-mediated input, the cellular sources originating these events
      remain unclear. However, a precise definition of the presynaptic GABAergic
      interneurons contacting Cajal-Retzius cells is important to understand the
      microcircuits and network patterns controlling their activation. Here, we have
      taken advantage of electrophysiological and anatomical techniques applied to
      mouse hippocampal slices in vitro to directly address this question. Our paired
      recording experiments indicate that Cajal-Retzius cells receive small-amplitude,
      kinetically slow synaptic input from stratum lacunosum-moleculare interneurons,
      anatomically identified as neurogliaform cells. In addition, a convergence of
      optogenetic, electrophysiological, and pharmacological experiments shows that
      Cajal-Retzius cells receive GABAergic input from oriens lacunosum-moleculare
      cells and that this input has different physiological properties (i.e., larger
      amplitude and faster kinetics) from the one provided by neurogliaform cells.
      Last, we show that GABAergic evoked synaptic input onto Cajal-Retzius cells may
      either increase their excitability and trigger action potentials or inhibit
      spontaneous firing by depolarization block. We propose that the specific type of
      response depends on both the membrane potential of Cajal-Retzius cells and the
      kinetics of the received GABAergic input. In conclusion, we have unraveled a
      novel hippocampal microcircuit with complex GABAergic synaptic signaling, which
      we suggest may play a role in the refinement of the hippocampal network and
      connections during development.

PMID- 23536065
TI  - Learning increases intrinsic excitability of hippocampal interneurons.
AB  - Learning-related intrinsic excitability changes of pyramidal neurons via
      modulation of the postburst afterhyperpolarization (AHP) have been repeatedly
      demonstrated in multiple brain regions (especially the hippocampus), after a
      variety of learning tasks, and in multiple species. While exciting and important,
      the changes in pyramidal neurons are only a part of the neural circuitry involved
      in successful learning. For a more complete picture of the dynamic learning
      related changes in the neural network, changes in inhibitory circuitry must also
      be systematically examined and characterized. Here we show in young adult rats
      and mice that learning the hippocampus-dependent trace eyeblink conditioning task
      induces enhanced inhibition onto CA1 pyramidal neurons mediated, in part, by an
      increase in intrinsic excitability of somatostatin-positive inhibitory neurons
      (SOMs). Furthermore, both CA1 pyramidal and SOM interneurons shared a common
      cellular mechanism (reduction in SK channel-mediated AHP) that led to the
      learning-induced increased intrinsic excitability.

PMID- 23536066
TI  - Dance of the SNAREs: assembly and rearrangements detected with FRET at neuronal
      synapses.
AB  - Soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors
      (SNAREs) mediate vesicle fusion with the plasma membrane on activation by calcium
      binding to synaptotagmin. In the present study, we used fluorescence resonance
      energy transfer (FRET) and fluorescence lifetime imaging microscopy between
      fluorescently labeled SNARE proteins expressed in cultured rat hippocampal
      neurons to detect resting SNARE complexes, their conformational rearrangement on
      exocytosis, their disassembly before endocytosis of vesicular proteins, and SNARE
      assembly at newly docked vesicles. Assembled SNAREs are not only present in
      docked vesicles; unexpected residual "orphan SNARE complexes" also reside in para
      active zone regions. Real-time changes in FRET between N-terminally labeled SNAP
      25 and VAMP reported a reorientation of the SNARE motif upon exocytosis, SNARE
      disassembly in the active zone periphery, and SNARE reassembly in newly docked
      vesicles. With VAMP labeled C-terminally, decreased fluorescence in C-terminally
      labeled syntaxin (extracellular) reported trans-cis-conformational changes in
      SNAREs on vesicle fusion. After fusion SNAP-25 and syntaxin disperse along with
      VAMP, as well as the FRET signal itself, indicating diffusion of intact SNAREs
      after vesicle fusion but before their peripheral disassembly. Our measurements of
      spatiotemporal dynamics of SNARE conformational changes and movements refine
      models of SNARE function. Technical advances required to detect tiny changes in
      fluorescence in small fractions of labeled proteins in presynaptic boutons on a
      time scale of seconds permit the detection of rapid intermolecular interactions
      between small proportions of protein partners in cellular subcompartments.

PMID- 23536067
TI  - ACR-12 ionotropic acetylcholine receptor complexes regulate inhibitory motor
      neuron activity in Caenorhabditis elegans.
AB  - Heterogeneity in the composition of neurotransmitter receptors is thought to
      provide functional diversity that may be important in patterning neural activity
      and shaping behavior (Dani and Bertrand, 2007; Sassoe-Pognetto, 2011). However,
      this idea has remained difficult to evaluate directly because of the complexity
      of neuronal connectivity patterns and uncertainty about the molecular composition
      of specific receptor types in vivo. Here we dissect how molecular diversity
      across receptor types contributes to the coordinated activity of excitatory and
      inhibitory motor neurons in the nematode Caenorhabditis elegans. We show that
      excitatory and inhibitory motor neurons express distinct populations of
      ionotropic acetylcholine receptors (iAChRs) requiring the ACR-12 subunit. The
      activity level of excitatory motor neurons is influenced through activation of
      nonsynaptic iAChRs (Jospin et al., 2009; Barbagallo et al., 2010). In contrast,
      synaptic coupling of excitatory and inhibitory motor neurons is achieved through
      a second population of iAChRs specifically localized at postsynaptic sites on
      inhibitory motor neurons. Loss of ACR-12 iAChRs from inhibitory motor neurons
      leads to reduced synaptic drive, decreased inhibitory neuromuscular signaling,
      and variability in the sinusoidal motor pattern. Our results provide new insights
      into mechanisms that establish appropriately balanced excitation and inhibition
      in the generation of a rhythmic motor behavior and reveal functionally diverse
      roles for iAChR-mediated signaling in this process.

PMID- 23536068
TI  - The cellular code for mammalian thermosensation.
AB  - Mammalian somatosenory neurons respond to thermal stimuli and allow animals to
      reliably discriminate hot from cold and to select their preferred environments.
      Previously, we generated mice that are completely insensitive to temperatures
      from noxious cold to painful heat (-5 to 55 degrees C) by ablating several
      different classes of nociceptor early in development. In the present study, we
      have adopted a selective ablation strategy in adult mice to study this phenotype
      and have demonstrated that separate populations of molecularly defined neurons
      respond to hot and cold. TRPV1-expressing neurons are responsible for all
      behavioral responses to temperatures between 40 and 50 degrees C, whereas TRPM8
      neurons are required for cold aversion. We also show that more extreme cold and
      heat activate additional populations of nociceptors, including cells expressing
      Mrgprd. Therefore, although eliminating Mrgprd neurons alone does not affect
      behavioral responses to temperature, when combined with ablation of TRPV1 or
      TRPM8 cells, it significantly decreases responses to extreme heat and cold,
      respectively. Ablation of TRPM8 neurons distorts responses to preferred
      temperatures, suggesting that the pleasant thermal sensation of warmth may in
      fact just reflect reduced aversive input from TRPM8 and TRPV1 neurons. As
      predicted by this hypothesis, mice lacking both classes of thermosensor exhibited
      neither aversive nor attractive responses to temperatures between 10 and 50
      degrees C. Our results provide a simple cellular basis for mammalian
      thermosensation whereby two molecularly defined classes of sensory neurons detect
      and encode both attractive and aversive cues.

PMID- 23536069
TI  - Efferent feedback minimizes cochlear neuropathy from moderate noise exposure.
AB  - Although protective effects of the cochlea's efferent feedback pathways have been
      well documented, prior work has focused on hair cell damage and cochlear
      threshold elevation and, correspondingly, on the high sound pressure levels (>100
      dB SPL) necessary to produce them. Here we explore the noise-induced loss of
      cochlear neurons that occurs with lower-intensity exposures and in the absence of
      permanent threshold shifts. Using confocal microscopy to count synapses between
      hair cells and cochlear nerve fibers, and using measurement of auditory brainstem
      responses and otoacoustic emissions to assess cochlear presynaptic and
      postsynaptic function, we compare the damage from a weeklong exposure to moderate
      level noise (84 dB SPL) in mice with varying degrees of cochlear de-efferentation
      induced by surgical lesion to the olivocochlear pathway. Such exposure causes
      minimal acute threshold shifts and no chronic shifts in mice with normal efferent
      feedback. In de-efferented animals, there was up to 40% loss of cochlear nerve
      synapses and a corresponding decline in the amplitude of the auditory brainstem
      response. Quantitative analysis of the de-efferentation in inner versus outer
      hair cell areas suggested that outer hair cell efferents are the most important
      in minimizing this neuropathy, presumably by virtue of their sound-evoked
      feedback reduction of cochlear amplification. The moderate nature of this
      acoustic overexposure suggests that cochlear neurons are at risk even in everyday
      acoustic environments, so the need for cochlear protection is plausible as a
      driving force in the design of this feedback pathway.

PMID- 23536070
TI  - Alzheimer's disease neurodegenerative biomarkers are associated with decreased
      cognitive function but not beta-amyloid in cognitively normal older individuals.
AB  - beta-Amyloid (Abeta) plaque deposition and neurodegeneration within
      temporoparietal and hippocampal regions may indicate increased risk of
      Alzheimer's disease (AD). This study examined relationships between AD biomarkers
      of Abeta and neurodegeneration as well as cognitive performance in cognitively
      normal older individuals. Abeta burden was quantified in 72 normal older human
      subjects from the Berkeley Aging Cohort (BAC) using [(11)C] Pittsburgh compound B
      (PIB) positron emission tomography. In the same individuals, we measured
      hippocampal volume, as well as glucose metabolism and cortical thickness, which
      were extracted from a template of cortical AD-affected regions. The three
      functional and structural biomarkers were merged into a highly AD-sensitive
      multimodality biomarker reflecting neural integrity. In the normal older
      individuals, there was no association between elevated PIB uptake and either the
      single-modality or the multimodality neurodegenerative biomarkers. Lower neural
      integrity within the AD-affected regions and a control area (the visual cortex)
      was related to lower scores on memory and executive function tests; the same
      association was not found with PIB retention. The relationship between cognition
      and the multimodality AD biomarker was stronger in individuals with the highest
      PIB uptake. The findings indicate that neurodegeneration occurs within AD regions
      regardless of Abeta deposition and accounts for worse cognition in cognitively
      normal older people. The impact of neural integrity on cognitive functions is,
      however, enhanced in the presence of high Abeta burden for brain regions that are
      most affected in AD.

PMID- 23536071
TI  - Variability of human corticospinal excitability tracks the state of action
      preparation.
AB  - Task-evoked trial-by-trial variability is a ubiquitous property of neural
      responses, yet its functional role remains largely unclear. Recent work in
      nonhuman primates shows that the temporal structure of neural variability in
      several brain regions is task-related. For example, trial-by-trial variability in
      premotor cortex tracks motor preparation with increasingly consistent firing
      rates and thus a decline in variability before movement onset. However, whether
      noninvasive measures of the variability of population activity available from
      humans can similarly track the preparation of actions remains unknown. We tested
      this by using single-pulse transcranial magnetic stimulation (TMS) over primary
      motor cortex (M1) to measure corticospinal excitability (CSE) at different times
      during action preparation. First, we established the basic properties of
      intrinsic CSE variability at rest. Then, during the task, responses (left or
      right button presses) were either directly instructed (forced choice) or resulted
      from a value decision (choice). Before movement onset, we observed a temporally
      specific task-related decline in CSE variability contralateral to the responding
      hand. This decline was stronger in fast-response compared with slow-response
      trials, consistent with data in nonhuman primates. For the nonresponding hand,
      CSE variability also decreased, but only in choice trials, and earlier compared
      with the responding hand, possibly reflecting choice-specific suppression of
      unselected actions. These findings suggest that human CSE variability measured by
      TMS over M1 tracks the state of motor preparation, and may reflect the
      optimization of preparatory population activity. This provides novel avenues in
      humans to assess the dynamics of action preparation but also more complex
      processes, such as choice-to-action transformations.

PMID- 23536072
TI  - Engineered deafness reveals that mouse courtship vocalizations do not require
      auditory experience.
AB  - Auditory experience during development is necessary for normal language
      acquisition in humans. Although songbirds, some cetaceans, and maybe bats may
      also be vocal learners, vocal learning has yet to be well established for a
      laboratory mammal. Mice are potentially an excellent model organism for studying
      mechanisms underlying vocal communication. Mice vocalize in different social
      contexts, yet whether they learn their vocalizations remains unresolved. To
      address this question, we compared ultrasonic courtship vocalizations emitted by
      chronically deaf and normal hearing adult male mice. We deafened CBA/CaJ male
      mice, engineered to express diphtheria toxin (DT) receptors in hair cells, by
      systemic injection of DT at postnatal day 2 (P2). By P9, almost all inner hair
      cells were absent and by P16 all inner and outer hair cells were absent in DTR
      mice. These mice did not show any auditory brainstem responses as adults. Wild
      type littermates, also treated with DT at P2, had normal hair cells and normal
      auditory brainstem responses. We compared the temporal structure of vocalization
      bouts, the types of vocalizations, the patterns of syllables, and the acoustic
      features of each syllable type emitted by hearing and deaf males in the presence
      of a female. We found that almost all of the vocalization features we examined
      were similar in hearing and deaf animals. These findings indicate that mice do
      not need auditory experience during development to produce normal ultrasonic
      vocalizations in adulthood. We conclude that mouse courtship vocalizations are
      not acquired through auditory feedback-dependent learning.

PMID- 23536073
TI  - Axonal translation of beta-catenin regulates synaptic vesicle dynamics.
AB  - Many presynaptic transcripts have been observed in axons, yet their role in
      synapse development remains unknown. Using visually and pharmacologically
      isolated presynaptic terminals from dissociated rat hippocampal neurons, we found
      that ribosomes and beta-catenin mRNA preferentially localize to recently formed
      boutons. Locally translated beta-catenin accumulates at presynaptic terminals,
      where it regulates synaptic vesicle release dynamics. Thus, local translation of
      beta-catenin is a newly described mechanism for axons to independently
      functionalize nerve terminals at great distances from cellular somata.

PMID- 23536074
TI  - Schwann cell LRP1 regulates remak bundle ultrastructure and axonal interactions
      to prevent neuropathic pain.
AB  - Trophic support and myelination of axons by Schwann cells in the PNS are
      essential for normal nerve function. Herein, we show that deletion of the LDL
      receptor-related protein-1 (LRP1) gene in Schwann cells (scLRP1(-/-)) induces
      abnormalities in axon myelination and in ensheathment of axons by nonmyelinating
      Schwann cells in Remak bundles. These anatomical changes in the PNS were
      associated with mechanical allodynia, even in the absence of nerve injury. In
      response to crush injury, sciatic nerves in scLRP1(-/-) mice showed accelerated
      degeneration and Schwann cell death. Remyelinated axons were evident 20 d after
      crush injury in control mice, yet were largely absent in scLRP1(-/-) mice. In the
      partial nerve ligation model, scLRP1(-/-) mice demonstrated significantly
      increased and sustained mechanical allodynia and loss of motor function. Evidence
      for central sensitization in pain processing included increased p38MAPK
      activation and activation of microglia in the spinal cord. These studies identify
      LRP1 as an essential mediator of normal Schwann cell-axonal interactions and as a
      pivotal regulator of the Schwann cell response to PNS injury in vivo. Mice in
      which LRP1 is deficient in Schwann cells represent a model for studying how
      abnormalities in Schwann cell physiology may facilitate and sustain chronic pain.

PMID- 23536077
TI  - Nitric oxide synthesis and cGMP production is important for neurite growth and
      synapse remodeling after axotomy.
AB  - Nitric oxide (NO) is an important signaling molecule with a variety of functions
      in the CNS, including a potential role in modulating neuronal growth and synapse
      formation. In the present study, we used tractable, identified neurons in the CNS
      of the pond snail Lymnaea stagnalis to study the role of endogenous NO signaling
      in neuronal growth and synaptic remodeling after nerve injury. Axonal damage of
      L. stagnalis neurons B1 and B2 induces extensive central growth of neurites that
      is accompanied by changes in existing electrical connections, the transient
      formation of novel electrical connections, and the formation of a novel
      excitatory chemical synapse from B2 to B1 neurons. Partial chronic inhibition of
      endogenous NO synthesis reduces neurite growth in NO-synthase-expressing B2, but
      has only minor effects on NOS-negative B1 neurons. Chronic application of an NO
      donor while inhibiting endogenous NO synthesis rescues neurite extension in B2
      neurons and boosts growth of B1 neurons. Blocking soluble guanylate cyclase
      activity completely suppresses neurite extension and synaptic remodeling after
      nerve crush, demonstrating the importance of cGMP in these processes.
      Interestingly, inhibition of cGMP-dependent protein kinase only suppresses
      chemical synapse formation without effects on neuronal growth and electrical
      synapse remodeling. We conclude that NO signaling via cGMP is an important
      modulator of both neurite growth and synaptic remodeling after nerve crush.
      However, differential effects of cGMP-dependent protein kinase inhibition on
      neurite growth and synaptic remodeling suggest that these effects are mediated by
      separate signaling pathways.

PMID- 23536075
TI  - TRPV1 and TRPA1 antagonists prevent the transition of acute to chronic
      inflammation and pain in chronic pancreatitis.
AB  - Visceral afferents expressing transient receptor potential (TRP) channels TRPV1
      and TRPA1 are thought to be required for neurogenic inflammation and development
      of inflammatory hyperalgesia. Using a mouse model of chronic pancreatitis (CP)
      produced by repeated episodes (twice weekly) of caerulein-induced AP (AP), we
      studied the involvement of these TRP channels in pancreatic inflammation and pain
      related behaviors. Antagonists of the two TRP channels were administered at
      different times to block the neurogenic component of AP. Six bouts of AP (over 3
      wks) increased pancreatic inflammation and pain-related behaviors, produced
      fibrosis and sprouting of pancreatic nerve fibers, and increased TRPV1 and TRPA1
      gene transcripts and a nociceptive marker, pERK, in pancreas afferent somata.
      Treatment with TRP antagonists, when initiated before week 3, decreased
      pancreatic inflammation and pain-related behaviors and also blocked the
      development of histopathological changes in the pancreas and upregulation of
      TRPV1, TRPA1, and pERK in pancreatic afferents. Continued treatment with TRP
      antagonists blocked the development of CP and pain behaviors even when mice were
      challenged with seven more weeks of twice weekly caerulein. When started after
      week 3, however, treatment with TRP antagonists was ineffective in blocking the
      transition from AP to CP and the emergence of pain behaviors. These results
      suggest: (1) an important role for neurogenic inflammation in pancreatitis and
      pain-related behaviors, (2) that there is a transition from AP to CP, after which
      TRP channel antagonism is ineffective, and thus (3) that early intervention with
      TRP channel antagonists may attenuate the transition to and development of CP
      effectively.

PMID- 23536076
TI  - Interhemispheric functional connectivity following prenatal or perinatal brain
      injury predicts receptive language outcome.
AB  - Early brain injury alters both structural and functional connectivity between the
      cerebral hemispheres. Despite increasing knowledge on the individual hemispheric
      contributions to recovery from such injury, we know very little about how their
      interactions affect this process. In the present study, we related
      interhemispheric structural and functional connectivity to receptive language
      outcome following early left hemisphere stroke. We used functional magnetic
      resonance imaging to study 14 people with neonatal brain injury, and 25 age
      matched controls during passive story comprehension. With respect to structural
      connectivity, we found that increased volume of the corpus callosum predicted
      good receptive language outcome, but that this is not specific to people with
      injury. In contrast, we found that increased posterior superior temporal gyrus
      interhemispheric functional connectivity during story comprehension predicted
      better receptive language performance in people with early brain injury, but
      worse performance in typical controls. This suggests that interhemispheric
      functional connectivity is one potential compensatory mechanism following early
      injury. Further, this pattern of results suggests refinement of the prevailing
      notion that better language outcome following early left hemisphere injury relies
      on the contribution of the contralesional hemisphere (i.e., the "right-hemisphere
      take-over" theory). This pattern of results was also regionally specific;
      connectivity of the angular gyrus predicted poorer performance in both groups,
      independent of brain injury. These results present a complex picture of recovery,
      and in some cases, such recovery relies on increased cooperation between the
      injured hemisphere and homologous regions in the contralesional hemisphere, but
      in other cases, the opposite appears to hold.

PMID- 23536078
TI  - Uncertainty increases pain: evidence for a novel mechanism of pain modulation
      involving the periaqueductal gray.
AB  - Predictions about sensory input exert a dominant effect on what we perceive, and
      this is particularly true for the experience of pain. However, it remains unclear
      what component of prediction, from an information-theoretic perspective, controls
      this effect. We used a vicarious pain observation paradigm to study how the
      underlying statistics of predictive information modulate experience. Subjects
      observed judgments that a group of people made to a painful thermal stimulus,
      before receiving the same stimulus themselves. We show that the mean observed
      rating exerted a strong assimilative effect on subjective pain. In addition, we
      show that observed uncertainty had a specific and potent hyperalgesic effect.
      Using computational functional magnetic resonance imaging, we found that this
      effect correlated with activity in the periaqueductal gray. Our results provide
      evidence for a novel form of cognitive hyperalgesia relating to perceptual
      uncertainty, induced here by vicarious observation, with control mediated by the
      brainstem pain modulatory system.

PMID- 23536079
TI  - Dissociable networks control conflict during perception and response selection: a
      transcranial magnetic stimulation Study.
AB  - Current models of conflict processing propose that cognitive control resolves
      conflict in the flanker task by enhancing task-relevant stimulus processing at a
      perceptual level. However, because conflicts occur at both a perceptual and a
      response selection level in that task, we tested the hypothesis of conflict
      specific control networks for perceptual and response selection conflicts using
      transcranial magnetic stimulation (TMS). TMS of the presupplementary motor area
      selectively disrupted the processing of response selection conflict, whereas TMS
      of the posterior intraparietal sulcus/inferior parietal lobule interfered with
      perceptual conflict processing. In more detail, the presupplementary motor area
      seems to resolve response selection conflict mainly when no conflicts have
      occurred in the previous trial. In contrast, the posterior intraparietal
      sulcus/inferior parietal lobule may resolve perceptual conflicts selectively when
      a conflict has occurred in the previous trial. The current data show the need for
      revising models of cognitive control by providing evidence for the existence of
      conflict-specific control networks resolving conflict at different processing
      levels.

PMID- 23536080
TI  - A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells
      promotes propriospinal axonal regeneration, synapse formation, and partial
      recovery of function after spinal cord injury.
AB  - Descending propriospinal neurons (DPSN) are known to establish functional relays
      for supraspinal signals, and they display a greater growth response after injury
      than do the long projecting axons. However, their regenerative response is still
      deficient due to their failure to depart from growth supportive cellular
      transplants back into the host spinal cord, which contains numerous impediments
      to axon growth. Here we report the construction of a continuous growth-promoting
      pathway in adult rats, formed by grafted Schwann cells overexpressing glial cell
      line-derived neurotrophic factor (GDNF). We demonstrate that such a growth
      promoting pathway, extending from the axonal cut ends to the site of innervation
      in the distal spinal cord, promoted regeneration of DPSN axons through and beyond
      the lesion gap of a spinal cord hemisection. Within the distal host spinal cord,
      regenerated DPSN axons formed synapses with host neurons leading to the
      restoration of action potentials and partial recovery of function.

PMID- 23536081
TI  - The countermanding task revisited: fast stimulus detection is a key determinant
      of psychophysical performance.
AB  - The countermanding task is a standard method for assessing cognitive/inhibitory
      control over action and for investigating its neural correlates. In it, the
      subject plans a movement and either executes it, if no further instruction is
      given, or attempts to prevent it, if a stop signal is shown. Through various
      experimental manipulations, many studies have sought to characterize the
      inhibitory mechanisms thought to be at work in the task, typically using an
      inferred, model-dependent metric called the stop-signal reaction time. This
      approach has consistently overlooked the impact of perceptual evaluation on
      performance. Through analytical work and computer simulations, here we show that
      psychophysical performance in the task can be easily understood as the result of
      an ongoing motor plan that is modified (decelerated) by the outcome of a rapid
      sensory detection process. Notably, no specific assumptions about hypothetical
      inhibitory mechanisms are needed. This modeling framework achieves four things:
      (1) it replicates and reconciles behavioral results in numerous variants of the
      countermanding task; (2) it provides a new, objective metric for characterizing
      task performance that is more effective than the stop-signal reaction time; (3)
      it shows that the time window over which detection of a high-visibility stimulus
      effectively occurs is extremely short (~20 ms); and (4) it indicates that
      modulating neuronal latencies and the buildup rates of developing motor plans are
      two key neural mechanisms for controlling action. The results suggest that
      manipulations of the countermanding task often cause changes in perceptual
      detection processes, and not necessarily in inhibition.

PMID- 23536082
TI  - A computational framework for understanding decision making through integration
      of basic learning rules.
AB  - Nonassociative and associative learning rules simultaneously modify neural
      circuits. However, it remains unclear how these forms of plasticity interact to
      produce conditioned responses. Here we integrate nonassociative and associative
      conditioning within a uniform model of olfactory learning in the honeybee.
      Honeybees show a fairly abrupt increase in response after a number of
      conditioning trials. The occurrence of this abrupt change takes many more trials
      after exposure to nonassociative trials than just using associative conditioning.
      We found that the interaction of unsupervised and supervised learning rules is
      critical for explaining latent inhibition phenomenon. Associative conditioning
      combined with the mutual inhibition between the output neurons produces an abrupt
      increase in performance despite smooth changes of the synaptic weights. The
      results show that an integrated set of learning rules implemented using fan-out
      connectivities together with neural inhibition can explain the broad range of
      experimental data on learning behaviors.

PMID- 23536083
TI  - A role for the medial temporal lobe in feedback-driven learning: evidence from
      amnesia.
AB  - The ability to learn from feedback is a key component of adaptive behavior. This
      type of learning is traditionally thought to depend on neural substrates in the
      striatum and not on the medial temporal lobe (MTL). Here we show that in humans
      the MTL becomes necessary for feedback-based learning when feedback is delayed.
      Specifically, amnesic patients with MTL damage were impaired at probabilistic
      learning of cue-outcome associations when response-contingent feedback was
      delayed by a few seconds, but not when feedback was immediate. By contrast,
      patients with striatal dysfunction due to Parkinson's disease demonstrated the
      opposite pattern: impaired learning when trial-by-trial feedback was immediate
      but not when feedback was delayed, indicating that the striatum is necessary for
      learning only when feedback is immediate. Together, these results reveal that
      multiple complementary learning processes support what appears to be identical
      behavior in healthy individuals and point to an important role for the MTL in
      feedback-driven learning.

PMID- 23536084
TI  - Fear conditioning enhances gamma oscillations and their entrainment of neurons
      representing the conditioned stimulus.
AB  - Learning alters the responses of neurons in the neocortex, typically
      strengthening their encoding of behaviorally relevant stimuli. These enhancements
      are studied extensively in the auditory cortex by characterizing changes in
      firing rates and evoked potentials. However, synchronous activity is also
      important for the processing of stimuli, especially the relationship between
      gamma oscillations in the local field potential and spiking. We investigated
      whether tone/shock fear conditioning in rats, a task known to alter responses in
      auditory cortex, also modified the relationship between gamma and unit activity.
      A boost in gamma oscillations developed, especially at sites tuned near the tone,
      and strengthened across multiple conditioning sessions. Unit activity became
      increasingly phase-locked to gamma, with sites tuned near the tone developing
      enhanced phase-locking during the tone, whereas those tuned away maintained a
      tendency to decrease their phase-locking. Enhancements in the coordination of
      spiking between sites tuned near the tone developed within the first conditioning
      session and remained throughout the rest of training. Enhanced cross-covariances
      in unit activity were strongest for subjects that exhibited robust conditioned
      fear. These results illustrate that changes in sensory cortex during associative
      learning extend to the coordination of neurons encoding the relevant stimulus,
      with implications for how it is processed downstream.

PMID- 23536085
TI  - The rat prefrontostriatal system analyzed in 3D: evidence for multiple
      interacting functional units.
AB  - Previous studies in monkeys disclosed a specific arrangement of corticostriatal
      projections. Prefrontal and premotor areas form dense projection fields
      surrounded by diffuse terminal areas extending outside the densely innervated
      region and overlapping with projections from other areas. In this study, the mode
      of prefrontostriatal innervation was analyzed in rats using a 3D approach.
      Following injections of tracers in defined cortical areas, 3D maps from
      individual cases were elaborated and combined into a global 3D map allowing us to
      define putative overlaps between projection territories. In addition to providing
      a detailed 3D mapping of the topographic representation of prefrontal cortical
      areas in the rat striatum, the results stress important similarities between the
      rodent and primate prefrontostriatal projections. They share the dual pattern of
      focal and diffuse corticostriatal projections. Moreover, besides segregated
      projections consistent with parallel processing, the interweaving of projection
      territories establishes specific patterns of overlaps spatially organized along
      the dorsoventral, mediolateral, and anteroposterior striatal axis. In particular,
      the extensive striatal projection fields from the prelimbic and anterior
      cingulate areas, which partly overlap the terminal fields from medial, orbital,
      and lateral prefrontal cortical areas, provide putative domains of convergence
      for integration between reward, cognitive, and motor processes.

PMID- 23536086
TI  - Adaptive temporal encoding leads to a background-insensitive cortical
      representation of speech.
AB  - Speech recognition is remarkably robust to the listening background, even when
      the energy of background sounds strongly overlaps with that of speech. How the
      brain transforms the corrupted acoustic signal into a reliable neural
      representation suitable for speech recognition, however, remains elusive. Here,
      we hypothesize that this transformation is performed at the level of auditory
      cortex through adaptive neural encoding, and we test the hypothesis by recording,
      using MEG, the neural responses of human subjects listening to a narrated story.
      Spectrally matched stationary noise, which has maximal acoustic overlap with the
      speech, is mixed in at various intensity levels. Despite the severe acoustic
      interference caused by this noise, it is here demonstrated that low-frequency
      auditory cortical activity is reliably synchronized to the slow temporal
      modulations of speech, even when the noise is twice as strong as the speech. Such
      a reliable neural representation is maintained by intensity contrast gain control
      and by adaptive processing of temporal modulations at different time scales,
      corresponding to the neural delta and theta bands. Critically, the precision of
      this neural synchronization predicts how well a listener can recognize speech in
      noise, indicating that the precision of the auditory cortical representation
      limits the performance of speech recognition in noise. Together, these results
      suggest that, in a complex listening environment, auditory cortex can selectively
      encode a speech stream in a background insensitive manner, and this stable neural
      representation of speech provides a plausible basis for background-invariant
      recognition of speech.

PMID- 23536088
TI  - Laterality and symmetry in rat olfactory behavior and in physiology of olfactory
      input.
AB  - Many species use bilateral sampling for odor-guided navigation. Bilateral
      localization strategies typically involve balanced and lateralized sensory input
      and early neuronal processing. For example, if gradient direction is estimated by
      differential sampling, then any asymmetry could bias the perceived direction.
      Subsequent neuronal processing can compensate for this asymmetry but requires the
      presence of mechanisms to track changes in asymmetry. A high degree of laterality
      is also important for differential sampling because spillover of signals will
      dilute the perceived odor gradient. In apparent contradiction to this model, both
      symmetry and laterality of nasal air flow have been reported to be incomplete in
      rats. Here, we measured symmetry and laterality in early olfactory processing in
      the rat. We first established behavioral readouts of precisely controlled
      bilateral odorant stimuli. We found that rats could rapidly and accurately report
      the direction of a wide range of odor gradients, presented in random sequence. We
      then showed that nasal air flow was symmetric over an entire day in awake rats.
      Furthermore, odor sampling from the two nostrils in the behavioral task was
      highly lateralized. This lateralization extended to the receptor epithelium
      responses as measured by electro-olfactograms. We finally observed strong
      lateralization of intrinsic signal responses from the glomerular layer of the
      olfactory bulb. We confirmed that a differential comparison of glomerular
      responses was sufficient to localize odorants. Together, these results suggest
      that the rat olfactory system is symmetric, with highly lateralized odor flow and
      neuronal responses. In combination, these attributes support odor localization by
      differential comparison.

PMID- 23536087
TI  - Oscillatory entrainment of primary somatosensory cortex encodes visual control of
      tactile processing.
AB  - Optimal behavior relies on the successful integration of complementary
      information from multiple senses. The neural mechanisms underlying multisensory
      interactions are still poorly understood. Here, we demonstrate the critical role
      of neural network oscillations and direct connectivity between primary sensory
      cortices in visual-somatosensory interactions. Extracellular recordings from all
      layers of the barrel field in Brown Norway rats in vivo showed that bimodal
      stimulation (simultaneous light flash and whisker deflection) augmented the
      somatosensory-evoked response and changed the power of induced network
      oscillations by resetting their phase. Anatomical tracing revealed sparse direct
      connectivity between primary visual (V1) and somatosensory (S1) cortices.
      Pharmacological silencing of V1 diminished but did not abolish cross-modal
      effects on S1 oscillatory activity, while leaving the early enhancement of the
      evoked response unaffected. Thus, visual stimuli seem to impact tactile
      processing by modulating network oscillations in S1 via corticocortical
      projections and subcortical feedforward interactions.

PMID- 23536089
TI  - Neuronal correlates of view representation revealed by face-view aftereffect.
AB  - Recognition of face-views is a crucial component of our social behavior. However,
      little is known about the neuronal basis of face-view recognition. Recent
      psychophysical studies have shown that adaptation to a particular face-view
      changes perception of other views in humans. To understand the neuronal basis of
      face-view representation and the mechanisms involved in face-view adaptation, we
      studied the responses of inferotemporal (IT) cortex neurons before and after face
      view adaptation. We first used face-view adaptation to show that monkeys, as well
      as humans, exhibit face-view aftereffect, suggesting the presence of a view
      sensitive representation in primates. Then, we recorded from IT neurons of
      monkeys and found that changes in responses of these neurons can account for
      changes in perception of face views attributable to adaptation, indicating IT as
      a neural correlate of face-view perception. More importantly, we provide evidence
      that IT neurons with wide-view tuning not only conveyed face-view information but
      also exhibited neural signatures of view aftereffect before neurons with narrower
      tuning. Our findings show that view-dependent representation of objects does not
      necessarily depend on narrow-tuned neurons. The finding that wide-view tuned
      neurons account for view-specific perceptual changes implies the importance of
      accumulating sensitivity and tolerance at the level of IT neurons, as the final
      stage of visual object recognition.

PMID- 23536091
TI  - The alpha crystallin domain of small heat shock protein b8 (Hspb8) acts as
      survival and differentiation factor in adult hippocampal neurogenesis.
AB  - Adult hippocampal neurogenesis is to a large degree controlled at the level of
      cell survival, and a number of potential mediators of this effect have been
      postulated. Here, we investigated the small heat shock protein Hspb8, which,
      because of its pleiotropic prosurvival effects in other systems, was considered a
      particularly promising candidate factor. Hspb8 is, for example, found in plaques
      of Alzheimer disease but exerts neuroprotective effects. We found that expression
      of Hspb8 increased during differentiation in vitro and was particularly
      associated with later stages (48-96 h) of differentiation. Gain-of-function and
      loss-of-function experiments supported the hypothesis that Hspb8 regulates cell
      survival of new neurons in vitro. In the dentate gyrus of adult mice in vivo,
      lentiviral overexpression of Hspb8 doubled the surviving cells and concomitantly
      promoted differentiation and net neurogenesis without affecting precursor cell
      proliferation. We also discovered that the truncated form of the crystallin
      domain of Hspb8 was sufficient to affect cell survival and neuronal
      differentiation in vitro and in vivo. Precursor cell experiments in vitro
      revealed that Hspb8 increases the phosphorylation of Akt and suggested that the
      prosurvival effect can be produced by a cell-autonomous mechanism. Analysis of
      hippocampal Hspb8 expression in mice of 69 strains of the recombinant inbred set
      BXD revealed that Hspb8 is a cis-acting gene whose expression was associated with
      clusters of transcript enriched in genes linked to growth factor signaling and
      apoptosis. Our results strongly suggest that Hspb8 and its alpha-crystallin
      domain might act as pleiotropic prosurvival factor in the adult hippocampus.

PMID- 23536090
TI  - Conditional disruption of calpain in the CNS alters dendrite morphology, impairs
      LTP, and promotes neuronal survival following injury.
AB  - Ubiquitous classical (typical) calpains, calpain-1 and calpain-2, are Ca(+2)
      dependent cysteine proteases, which have been associated with numerous
      physiological and pathological cellular functions. However, a clear understanding
      of the role of calpains in the CNS has been hampered by the lack of appropriate
      deletion paradigms in the brain. In this study, we describe a unique model of
      conditional deletion of both calpain-1 and calpain-2 activities in mouse brain,
      which more definitively assesses the role of these ubiquitous proteases in brain
      development/function and pathology. Surprisingly, we show that these calpains are
      not critical for gross CNS development. However, calpain-1/calpain-2 loss leads
      to reduced dendritic branching complexity and spine density deficits associated
      with major deterioration in hippocampal long-term potentiation and spatial
      memory. Moreover, calpain-1/calpain-2-deficient neurons were significantly
      resistant to injury induced by excitotoxic stress or mitochondrial toxicity.
      Examination of downstream target showed that the conversion of the Cdk5
      activator, p35, to pathogenic p25 form, occurred only in the presence of calpain
      and that it played a major role in calpain-mediated neuronal death. These
      findings unequivocally establish two central roles of calpain-1/calpain-2 in CNS
      function in plasticity and neuronal death.

PMID- 23536092
TI  - Hierarchical learning induces two simultaneous, but separable, prediction errors
      in human basal ganglia.
AB  - Studies suggest that dopaminergic neurons report a unitary, global reward
      prediction error signal. However, learning in complex real-life tasks, in
      particular tasks that show hierarchical structure, requires multiple prediction
      errors that may coincide in time. We used functional neuroimaging to measure
      prediction error signals in humans performing such a hierarchical task involving
      simultaneous, uncorrelated prediction errors. Analysis of signals in a priori
      anatomical regions of interest in the ventral striatum and the ventral tegmental
      area indeed evidenced two simultaneous, but separable, prediction error signals
      corresponding to the two levels of hierarchy in the task. This result suggests
      that suitably designed tasks may reveal a more intricate pattern of firing in
      dopaminergic neurons. Moreover, the need for downstream separation of these
      signals implies possible limitations on the number of different task levels that
      we can learn about simultaneously.

PMID- 23536093
TI  - Purkinje cell ataxin-1 modulates climbing fiber synaptic input in developing and
      adult mouse cerebellum.
AB  - Previous studies indicate that while transgenic mice with ATXN1[30Q]-D776-induced
      disease share pathological features caused by ATXN1[82Q] having an expanded
      polyglutamine tract, they fail to manifest the age-related progressive
      neurodegeneration seen in spinocerebellar ataxia type 1. The shared features
      include morphological alterations in climbing fiber (CF) innervation of Purkinje
      cells (PCs). To further investigate the ability of ataxin-1 (ATXN1) to impact
      CF/PC innervation, this study used morphological and functional approaches to
      examine CF/PC innervation during postnatal development in ATXN1[30Q]-D776 and
      ATXN1[82Q] cerebella. Notably, ATXN1[30Q]-D776 induced morphological alterations
      consistent with the development of the innervation of PCs by CFs being
      compromised, including a reduction of CF translocation along the PC dendritic
      tree, and decreased pruning of CF terminals from the PC soma. As previously shown
      for ATXN1[82Q], ATXN1[30Q]-D776 must enter the nucleus of PCs to induce these
      alterations. Experiments using conditional ATXN1[30Q]-D776 mice demonstrate that
      both the levels and specific timing of mutant ATXN1 expression are critical for
      alteration of the CF-PC synapse. Together these observations suggest that ATXN1,
      expressed exclusively in PCs, alters expression of a gene(s) in the postsynaptic
      PC that are critical for its innervation by CFs. To investigate whether
      ATXN1[30Q]-D776 curbs the progressive disease in ATXN1[82Q]-S776 mice, we crossed
      ATXN1[30Q]-D776 and ATXN1[82Q]-S776 mice and found that double transgenic mice
      developed progressive PC atrophy. Thus, the results also show that to develop
      progressive cerebellar degeneration requires expressing ATXN1 with an expanded
      polyglutamine tract.

PMID- 23536094
TI  - MicroRNA-276a functions in ellipsoid body and mushroom body neurons for naive and
      conditioned olfactory avoidance in Drosophila.
AB  - MicroRNA (miRNA)-mediated gene regulation plays a key role in brain development
      and function. But there are few cases in which the roles of individual miRNAs
      have been elucidated in behaving animals. We report a miR-276a::DopR regulatory
      module in Drosophila that functions in distinct circuits for naive odor responses
      and conditioned odor memory. Drosophila olfactory aversive memory involves
      convergence of the odors (conditioned stimulus) and the electric shock
      (unconditioned stimulus) in mushroom body (MB) neurons. Dopamine receptor DopR
      mediates the unconditioned stimulus inputs onto MB. Distinct dopaminergic neurons
      also innervate ellipsoid body (EB), where DopR function modulates arousal to
      external stimuli. We demonstrate that miR-276a is required in MB neurons for
      memory formation and in EB for naive responses to odors. Both roles of miR-276a
      are mediated by tuning DopR expression. The dual role of this miR-276a::DopR
      genetic module in these two neural circuits highlights the importance of miRNA
      mediated gene regulation within distinct circuits underlying both naive
      behavioral responses and memory.

PMID- 23536096
TI  - Coordinated population activity underlying texture discrimination in rat barrel
      cortex.
AB  - Rodents can robustly distinguish fine differences in texture using their
      whiskers, a capacity that depends on neuronal activity in primary somatosensory
      "barrel" cortex. Here we explore how texture was collectively encoded by
      populations of three to seven neuronal clusters simultaneously recorded from
      barrel cortex while a rat performed a discrimination task. Each cluster
      corresponded to the single-unit or multiunit activity recorded at an individual
      electrode. To learn how the firing of different clusters combines to represent
      texture, we computed population activity vectors across moving time windows and
      extracted the signal available in the optimal linear combination of clusters. We
      quantified this signal using receiver operating characteristic analysis and
      compared it to that available in single clusters. Texture encoding was
      heterogeneous across neuronal clusters, and only a minority of clusters carried
      signals strong enough to support stimulus discrimination on their own. However,
      jointly recorded groups of clusters were always able to support texture
      discrimination at a statistically significant level, even in sessions where no
      individual cluster represented the stimulus. The discriminative capacity of
      neuronal activity was degraded when error trials were included in the data,
      compared to only correct trials, suggesting a link between the neuronal activity
      and the animal's performance. These analyses indicate that small groups of barrel
      cortex neurons can robustly represent texture identity through synergistic
      interactions, and suggest that neurons downstream to barrel cortex could extract
      texture identity on single trials through simple linear combination of barrel
      cortex responses.

PMID- 23536095
TI  - Central dopamine D2 receptors regulate growth-hormone-dependent body growth and
      pheromone signaling to conspecific males.
AB  - Competition between adult males for limited resources such as food and receptive
      females is shaped by the male pattern of pituitary growth hormone (GH) secretion
      that determines body size and the production of urinary pheromones involved in
      male-to-male aggression. In the brain, dopamine (DA) provides incentive salience
      to stimuli that predict the availability of food and sexual partners. Although
      the importance of the GH axis and central DA neurotransmission in social
      dominance and fitness is clearly appreciated, the two systems have always been
      studied unconnectedly. Here we conducted a cell-specific genetic dissection study
      in conditional mutant mice that selectively lack DA D2 receptors (D2R) from
      pituitary lactotropes (lacDrd2KO) or neurons (neuroDrd2KO). Whereas lacDrd2KO
      mice developed a normal GH axis, neuroDrd2KO mice displayed fewer somatotropes;
      reduced hypothalamic Ghrh expression, pituitary GH content, and serum IGF-I
      levels; and exhibited reduced body size and weight. As a consequence of a GH axis
      deficit, neuroDrd2KO adult males excreted low levels of major urinary proteins
      and their urine failed to promote aggression and territorial behavior in control
      male challengers, in contrast to the urine taken from control adult males. These
      findings reveal that central D2Rs mediate a neuroendocrine-exocrine cascade that
      controls the maturation of the GH axis and downstream signals that are critical
      for fitness, social dominance, and competition between adult males.

PMID- 23536097
TI  - Retinoic acid deficiency impairs the vestibular function.
AB  - The retinaldehyde dehydrogenase 3 (Raldh3) gene encodes a major retinoic acid
      synthesizing enzyme and is highly expressed in the inner ear during
      embryogenesis. We found that mice deficient in Raldh3 bear severe impairment in
      vestibular functions. These mutant mice exhibited spontaneous circling/tilted
      behaviors and performed poorly in several vestibular-motor function tests. In
      addition, video-oculography revealed a complete loss of the maculo-ocular reflex
      and a significant reduction in the horizontal angular vestibulo-ocular reflex,
      indicating that detection of both linear acceleration and angular rotation were
      compromised in the mutants. Consistent with these behavioral and functional
      deficiencies, morphological anomalies, characterized by a smaller vestibular
      organ with thinner semicircular canals and a significant reduction in the number
      of otoconia in the saccule and the utricle, were consistently observed in the
      Raldh3 mutants. The loss of otoconia in the mutants may be attributed, at least
      in part, to significantly reduced expression of Otop1, which encodes a protein
      known to be involved in calcium regulation in the otolithic organs. Our data thus
      reveal a previously unrecognized role of Raldh3 in structural and functional
      development of the vestibular end organs.

PMID- 23536099
TI  - The Arab Spring: confronting the challenge of non-communicable disease.
AB  - This Commentary considers the health system and policy challenges of addressing
      non-communicable diseases (NCDs) in Egypt, Libya, and Tunisia, countries in the
      process of re-framing state policies and institutions, including in the health
      sector. Against this backdrop, a neglected issue of the rapidly rising burden of
      NCDs threatens both health and economic development. Tackling this worrisome rise
      in NCDs has been impeded by inadequate policies. Weak health systems, little
      attention to determinants of health, and limited access to affordable health care
      complicate effective responses to NCDs, especially in a fragile transitional
      phase. There remains an opportunity to confront the neglected challenge of NCDs
      by substantially strengthening policies and scaling up comprehensive health
      systems to more effectively address the causes and treatment of NCDs, including
      mental health, ultimately to improve population health overall.

PMID- 23536100
TI  - Commentary: learning all the lessons: expanding access to malaria diagnosis and
      treatment.
AB  - An independent evaluation of the Affordable Medicine Facility for malaria (AMFm)
      pilot phase has hailed it as a success, but important limitations and unanswered
      questions remain. In 2012, the board of the Global Fund decided to integrate the
      AMFm into country grants by 2014. This means that countries now need to determine
      how much of available grant resources to spend on expanding access through the
      public sector and how much, if any, on subsidizing drugs in the private, for
      profit sector. The assumption of the AMFm has assumed that improving delivery of
      artemisinin-based combination therapy through the private sector would be more
      efficient than further expanding access through the public sector and community
      health workers. But, the advantage of expanding and improving service delivery
      through the public sector and community health workers is that treatments can be
      effectively linked with diagnosis and that diagnosis and treatment can be offered
      for free.

PMID- 23536098
TI  - Simultaneous monitoring of presynaptic transmitter release and postsynaptic
      receptor trafficking reveals an enhancement of presynaptic activity in
      metabotropic glutamate receptor-mediated long-term depression.
AB  - Although the contribution of postsynaptic mechanisms to long-term synaptic
      plasticity has been studied extensively, understanding the contribution of
      presynaptic modifications to this process lags behind, primarily because of a
      lack of techniques with which to directly and quantifiably measure
      neurotransmitter release from synaptic terminals. Here, we developed a method to
      measure presynaptic activity through the biotinylation of vesicular transporters
      in vesicles fused with presynaptic membranes during neurotransmitter release.
      This method allowed us for the first time to selectively quantify the spontaneous
      or evoked release of glutamate or GABA at their respective synapses. Using this
      method to investigate presynaptic changes during the expression of group I
      metabotropic glutamate receptor (mGluR1/5)-mediated long-term depression (LTD) in
      cultured rat hippocampal neurons, we discovered that this form of LTD was
      associated with increased presynaptic release of glutamate, despite reduced
      miniature EPSCs measured with whole-cell recording. Moreover, we found that
      specific blockade of AMPA receptor (AMPAR) endocytosis with a membrane-permeable
      GluR2-derived peptide not only prevented the expression of LTD but also
      eliminated LTD-associated increase in presynaptic release. Thus, our work not
      only demonstrates that mGluR1/5-mediated LTD is associated with increased
      endocytosis of postsynaptic AMPARs but also reveals an unexpected
      homeostatic/compensatory increase in presynaptic release. In addition, this study
      indicates that biotinylation of vesicular transporters in live cultured neurons
      is a valuable tool for studying presynaptic function.

PMID- 23536101
TI  - Prospective evaluation of early follow-up chest radiography after penetrating
      thoracic injury.
AB  - BACKGROUND: In asymptomatic patients with penetrating thoracic trauma and a
      normal initial chest x-ray, successive prospective trials have decreased the
      minimum observation period required for exclusion of significant injury from 6 to
      3 h. Despite the quality of these studies, this interval remains arbitrary and
      the true requisite observation time for safe discharge remains unknown. The
      current study evaluates the ability of "early" repeat chest x-ray, at intervals
      approaching 1 h, to exclude clinically significant injury. METHODS: Eighty-eight,
      asymptomatic patients with penetrating chest trauma and normal initial chest
      radiographs were prospectively enrolled in this study. All patients received an
      "early" follow-up chest x-ray, at a median interval of 1 h and 34 min
      (interquartile range: 1 h 35 min to 2 h 22 min), and a second repeat x-ray at a
      "delayed" interval no earlier than 3 h postadmission. Radiographic abnormalities
      in clinically stable patients were followed with serial examination and repeat
      imaging for a minimum of 6 h. All patients received both "early" and "delayed"
      repeat CXRs with no patient discharged before full assessment. RESULTS: One of
      the 88 patients with initially normal chest x-ray underwent tube thoracostomy at
      the discretion of the attending surgeon before any repeat imaging. Of the
      remaining patients, 4 of 87 (4.6 %) demonstrated radiographic abnormalities on
      "early" repeat imaging. Two patients had pneumothoraces, successfully managed
      without intervention; the remaining two demonstrated evidence of hemothorax,
      subsequently undergoing tube thoracostomy. Two more patients (2.3 %) developed
      pneumothoraces on "delayed" imaging, both successfully observed without
      intervention. CONCLUSIONS: In asymptomatic patients with penetrating thoracic
      trauma and normal initial chest radiographs, "early" repeat chest x-ray, at
      intervals approaching 1 h, appears sufficient to exclude clinically significant
      pathology and to allow safe patient discharge.

PMID- 23536102
TI  - An expedient stereoselective and chemoselective synthesis of bicyclic
      oxazolidinones from quinols and isocyanates.
AB  - A mild and efficient synthesis of bicyclic oxazolidinones from quinols and
      isocyanates, under DBU-mediated conditions at room temperature, is described. The
      aza-Michael addition to substituted cyclohexadienones is stereoselective and
      chemoselective.

PMID- 23536103
TI  - Puerperal morbidity following repeat cesarean delivery in twin pregnancies.
AB  - OBJECTIVE: To evaluate the puerperal complications following twin deliveries.
      STUDY DESIGN: We conducted a population-based analysis of puerperal delivery
      related complications of twins born in Slovenia for comparing three groups of
      births (vaginal, elective and emergent cesarean). RESULTS: A total of 1,001
      elective, 1,109 emergent cesarean sections, and 2,204 vaginal twin births were
      evaluated. No differences were found between the complications after emergent and
      elective cesareans. Uterine atony was more frequent after vaginal births (OR 1.8
      2.0, 95 % CI 1.1-1.2, 2.9-3.3). Vaginal births had a higher frequency of
      endometritis compared with elective cesarean (OR 4.1, 95 % CI 1.2, 13.6).
      Conversely, vaginal deliveries were less frequently associated with anemia,
      hematoma formation, and need for blood transfusion as compared to both modes of
      cesarean deliveries. CONCLUSION: No solid data exist to show a clear advantage or
      disadvantage in terms of puerperal complications of an elective cesarean over
      vaginal birth for twins.

PMID- 23536104
TI  - Glucose enhancement of event-related potentials associated with episodic memory
      and attention.
AB  - Previous studies have reported that increasing glycaemia by a glucose-containing
      drink enhances memory functioning. The aim of the present study was to extend
      this literature by examining the effects of glucose on episodic memory as well as
      attention processes, and to investigate associated event-related potential (ERP)
      markers. Fifteen minutes after treatment (25 g glucose or placebo drink), 35
      participants performed an old/new recognition memory task and a Stroop colour
      naming task. Consistent with previous research, when controlling for glucose
      regulation, cognitive facilitation was observed behaviourally for verbal memory,
      but there was also a trend towards attentional facilitation. Furthermore, across
      both domains, it was the most demanding task conditions that exhibited glucose
      sensitivity. In support of the behavioural results, the analysis of ERPs across
      treatment groups revealed an enhanced left-parietal old/new effect related to
      recollection, and also suggested modulation of attentional processes. The results
      suggest that glucose may facilitate attention as well as memory.

PMID- 23536105
TI  - Effects of varenicline and bupropion sustained-release use plus intensive smoking
      cessation counseling on prolonged abstinence from smoking and on depression,
      negative affect, and other symptoms of nicotine withdrawal.
AB  - IMPORTANCE: Given the actions of varenicline tartrate and bupropion hydrochloride
      sustained-release (SR) on neurobiological targets related to affect and reward,
      it is thought that the modulation of nicotine withdrawal symptoms may contribute
      to their effectiveness. OBJECTIVE: To assess the relative efficacy of varenicline
      and bupropion SR plus intensive counseling on smoking cessation and emotional
      functioning. DESIGN AND SETTING: Placebo-controlled randomized clinical trial at
      a university medical center. PARTICIPANTS: In total, 294 community volunteers who
      wanted to quit smoking. INTERVENTIONS: Twelve weeks of varenicline, bupropion SR,
      or placebo plus intensive smoking cessation counseling (10 sessions, for a total
      of approximately 240 minutes of counseling). MAIN OUTCOME MEASURES: Prolonged
      abstinence from smoking and weekly measures of depression, negative affect, and
      other symptoms of nicotine withdrawal. RESULTS: Significant differences were
      found in abstinence at the end of treatment and through the 3-month postquit
      follow-up visit, favoring both active medications compared with placebo. At the 6
      month postquit follow-up visit, only the varenicline vs placebo comparison
      remained significant. Varenicline use was also associated with a generalized
      suppression of depression and reduced smoking reward compared with the other
      treatments, while both active medications improved concentration, reduced
      craving, and decreased negative affect and sadness compared with placebo, while
      having little effect (increase or decrease) on anxiety and anger. No differences
      were noted in self-reported rates of neuropsychiatric adverse events. CONCLUSIONS
      AND RELEVANCE: In a community sample, varenicline exerts a robust and favorable
      effect on smoking cessation relative to placebo and may have a favorable
      (suppressive) effect on symptoms of depression and other affective measures, with
      no clear unfavorable effect on neuropsychiatric adverse events. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00507728.

PMID- 23536106
TI  - Worldwide analysis of factors associated with medicines compendia publishing.
AB  - BACKGROUND: Medicines compendia, also called formularies, are the most commonly
      used drug information source among health care professionals. OBJECTIVE: The aim
      was to identify the countries publishing medicines compendia and the socio
      demographic factors associated to this fact. Additionally, we sought to determine
      the use of foreign compendia in countries lacking their own. SETTING: Global web
      based survey. METHOD: Healthcare practitioners and researchers from 193 countries
      worldwide were invited to complete a web-based survey. The questionnaire
      investigated the existence of a national compendium, or the use of foreign
      compendia in the absence of one. Demographic and socioeconomic variables were
      used to predict compendia publishing through a multivariate analysis. MAIN
      OUTCOME MEASURE: Existence of national medicines compendia and foreign compendia
      used. RESULTS: Professionals from 132 countries completed the survey (response
      rate at a country level 68.4%, comprising 90.9% global population). Eighty-four
      countries (63.6%) reported publishing a medicines compendium. In the multivariate
      analysis, only two covariates had significant association with compendia
      publishing. Being a member of the Organisation for the Economic Cooperation and
      Development was the only variable positively associated with compendia publishing
      (OR = 37.5; 95% CI = 2.3:599.8). In contrast, the countries that listed French as
      an official language were less likely to publish a compendium (OR = 0.07; 95% CI
      = 0.007:0.585). Countries without national compendia reported using the British
      National Formulary most commonly, followed by the Dictionnaire Vidal. CONCLUSION:
      Publication of medicines compendia is associated with socio-economic development.
      Countries lacking a national compendium, use foreign compendia from higher-income
      countries. Creating an international medicines compendium under the leadership of
      the World Health Organisation, rather than merely a 'model', would reduce the
      risks of using information sources not-adapted to the necessities of developing
      countries.

PMID- 23536107
TI  - A retrospective observational analysis to evaluate the off-label use of
      bevacizumab alone or with irinotecan in recurrent glioblastoma.
AB  - BACKGROUND: Recurrent glioblastoma is nearly always fatal, with median survival
      rates of approximately 12-14 months. Previous phase II clinical trials showed
      promising results with bevacizumab, alone or in combination with irinotecan, in
      patients with recurrent glioblastoma. OBJECTIVE: To assess whether the survival
      of patients with recurrent glioblastoma receiving bevacizumab alone or with
      irinotecan in everyday practice is comparable to that reported in clinical
      trials. SETTING: This was a retrospective observational study conducted at a
      single hospital in Italy. METHOD: Patients with recurrent glioblastoma who had
      received bevacizumab alone or with irinotecan from January 2009 to September 2011
      were included in our study. MAIN OUTCOME MEASURE: Progression-free survival (PFS)
      and overall survival (OS), and rates of PFS and OS at 6 months. RESULTS: Median
      PFS was 5.1 months in the bevacizumab group (n = 9) and 15.4 months in the
      bevacizumab + irinotecan group (n = 10), with 6-month PFS rates of 45 and 69%,
      respectively. Median OS was 6.8 months for bevacizumab alone and 11.1 months for
      bevacizumab + irinotecan, with 6-month OS rates of 100 and 90%, respectively.
      CONCLUSION: Although the number of patients included is not sufficient to allow a
      conclusive statement about the place of bevacizumab in the treatment of recurrent
      glioblastoma, the data appear promising, and are consistent with the results of
      clinical trials.

PMID- 23536109
TI  - AMP-activated protein kinase-mediated glucose transport as a novel target of
      tributyltin in human embryonic carcinoma cells.
AB  - Organotin compounds such as tributyltin (TBT) are known to cause various forms of
      cytotoxicity, including developmental toxicity and neurotoxicity. However, the
      molecular target of the toxicity induced by nanomolar levels of TBT has not been
      identified. In the present study, we found that exposure to 100 nM TBT induced
      growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since
      glucose provides metabolic energy, we focused on the glycolytic system. We found
      that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose
      6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined
      glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a
      decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the
      effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose
      transport by facilitating GLUT translocation. Treatment with the potent AMPK
      activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1
      and glucose uptake. In conclusion, these results suggest that exposure to
      nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in
      human embryonic carcinoma cells. Thus, understanding the energy metabolism may
      provide new insights into the mechanisms of metal-induced cytotoxicity.

PMID- 23536108
TI  - Omega-3 polyunsaturated fatty acids delay the progression of endotoxic shock
      induced myocardial dysfunction.
AB  - Septic shock has a high mortality rate, partially related to myocardial
      dysfunction. Polyunsaturated fatty acids (omega-3 PUFAs) possess anti
      inflammatory and antioxidant properties, but whether omega-3 PUFAs exert
      beneficial effects on myocardial function is unknown. We investigated, in a rat
      model of endotoxic shock, the effects of omega-3 PUFAs pretreatment on cardiac
      hemodynamics, function, and oxidative stress as well as intestinal barrier.
      Endotoxic shock was induced by lipopolysaccharide (LPS; 20 mg/kg IP) administered
      to rats pretreated or not with omega-3 PUFAs (Omegaven(r); 0.5 g/kg IP, 90 min
      before injection of LPS). Two or 5 h after LPS, left ventricular function and
      arterial pressure were measured, followed by assessment left ventricular total
      glutathione as well as tumor necrosis factor alpha expression, occuldin
      expression, and proteasome activities. LPS reduced mean arterial blood pressure
      to the same extent 2 and 5 h after its administration, but cardiac output was
      more markedly decreased after 5 h. Omega-3 PUFAs pretreatment did not
      significantly modify the effect of LPS on mean arterial pressure and total
      peripheral resistance, but prevented the decrease in cardiac output 2 h after
      LPS. LPS increased oxidized glutathione after 2 h, and this increase was
      significantly attenuated by omega-3 PUFAs. Simultaneously, omega-3 PUFAs
      increased myocardial hemeoxygenase-1 (HO-1) mRNA expression. Finally, omega-3
      PUFAs prevented the reduction of intestinal occludin expression. Omega-3 PUFAs
      pre-treatment improves myocardial dysfunction during endotoxemia and increases
      myocardial HO-1 expression. Moreover, the preservation of the intestinal occludin
      induced by omega-3 PUFAs precedes myocardial protection, suggesting the
      involvement of the intestinal barrier in the myocardial improvement observed with
      omega-3 PUFAs parenteral supplementation.

PMID- 23536110
TI  - The potential role of iodine-123 metaiodobenzylguanidine imaging for identifying
      sustained ventricular tachycardia in patients with cardiomyopathy.
AB  - Implantable cardioverter-defibrillators (ICDs) significantly reduce mortality in
      patients with depressed left ventricular ejection fraction (LVEF) and heart
      failure (HF). However, shortcomings of LVEF to accurately identify those at
      greatest risk of ventricular tachyarrhythmias have led to the pursuit of
      alternative means to refine qualification criteria for ICD implantation. It is
      well established that imaging the cardiac nervous system with(123)I meta
      iodobenzylguanidine ((123)I-mIBG) provides incremental prognostic value in
      patients with HF beyond LVEF. Whether (123)I-mIBG will also play an important
      role for identifying and/or predicting sustained ventricular tachyarrhythmias in
      patients with cardiomyopathy and determining those who may benefit from ICD
      implantation is currently under investigation. Novel imaging approaches that
      pinpoint the site of ventricular arrhythmias and guide ventricular tachycardia
      ablation are presented.

PMID- 23536111
TI  - Recurrence quantification analysis of human postural fluctuations in older
      fallers and non-fallers.
AB  - We investigate postural sway data dynamics in older adult fallers and non
      fallers. Center of pressure (COP) signals were recorded during quiet standing in
      28 older adults. The subjects were divided in two groups: with and without
      history of falls. COP time series were analyzed using recurrence quantification
      analysis (RQA) in both anteroposterior and mediolateral (ML) directions.
      Classical stabilometric variables (path length and range) were also computed. The
      results showed that RQA outputs quantifying predictability of COP fluctuations
      and Shannon entropy of recurrence plot diagonal line length distribution, were
      significantly higher in fallers, only for ML direction. In addition, the range of
      ML COP signals was also significantly higher in fallers. This result is in
      accordance with some findings of the literature and could be interpreted as an
      increased hip strategy in fallers. The RQA results seem coherent with the theory
      of loss of complexity with aging and disease. Our results suggest that RQA is a
      promising approach for the investigation of COP fluctuations in a frail
      population. 

PMID- 23536113
TI  - Identification of resting and active state EEG features of Alzheimer's disease
      using discrete wavelet transform.
AB  - Alzheimer's disease (AD) is associated with deficits in a number of cognitive
      processes and executive functions. Moreover, abnormalities in the
      electroencephalogram (EEG) power spectrum develop with the progression of AD.
      These features have been traditionally characterized with montage recordings and
      conventional spectral analysis during resting eyes-closed and resting eyes-open
      (EO) conditions. In this study, we introduce a single lead dry electrode EEG
      device which was employed on AD and control subjects during resting and activated
      battery of cognitive and sensory tasks such as Paced Auditory Serial Addition
      Test (PASAT) and auditory stimulations. EEG signals were recorded over the left
      prefrontal cortex (Fp1) from each subject. EEG signals were decomposed into sub
      bands approximately corresponding to the major brain frequency bands using
      several different discrete wavelet transforms and developed statistical features
      for each band. Decision tree algorithms along with univariate and multivariate
      statistical analysis were used to identify the most predictive features across
      resting and active states, separately and collectively. During resting state
      recordings, we found that the AD patients exhibited elevated D4 (~4-8 Hz) mean
      power in EO state as their most distinctive feature. During the active states,
      however, the majority of AD patients exhibited larger minimum D3 (~8-12 Hz)
      values during auditory stimulation (18 Hz) combined with increased kurtosis of D5
      (~2-4 Hz) during PASAT with 2 s interval. When analyzed using EEG recording data
      across all tasks, the most predictive AD patient features were a combination of
      the first two feature sets. However, the dominant discriminating feature for the
      majority of AD patients were still the same features as the active state
      analysis. The results from this small sample size pilot study indicate that
      although EEG recordings during resting conditions are able to differentiate AD
      from control subjects, EEG activity recorded during active engagement in
      cognitive and auditory tasks provide important distinct features, some of which
      may be among the most predictive discriminating features.

PMID- 23536114
TI  - Best practices for team-based assistive technology design courses.
AB  - Team-based design courses focused on products for people with disabilities have
      become relatively common, in part because of training grants such as the NSF
      Research to Aid Persons with Disabilities course grants. An output from these
      courses is an annual description of courses and projects but has yet to be
      complied into a "best practices guide," though it could be helpful for
      instructors. To meet this need, we conducted a study to generate best practices
      for assistive technology product development courses and how to use these courses
      to teach students the fundamentals of innovation. A full list of recommendations
      is comprised in the manuscript and include identifying a client through a
      reliable clinical partner; allowing for transparency between the instructors, the
      client, and the team(s); establishing multi-disciplinary teams; using a process
      oriented vs. solution-oriented product development model; using a project
      management software to facilitate and archive communication and outputs;
      facilitating client interaction through frequent communication; seeking to
      develop professional role confidence to inspire students' commitment to
      engineering and (where applicable) rehabilitation field; publishing student
      designs on repositories; incorporating both formal and informal education
      opportunities related to design; and encouraging students to submit their designs
      to local or national entrepreneurship competitions. 

PMID- 23536112
TI  - Gender-dependence of bone structure and properties in adult osteogenesis
      imperfecta murine model.
AB  - Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by
      bone fragility and deformities. Though the oim mouse model has been the most
      widely studied of the OI models, it has only recently been suggested to exhibit
      gender-dependent differences in bone mineralization. To characterize the impact
      of gender on the morphometry/ultra-structure, mechanical properties, and
      biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month
      old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated
      using micro-computed tomography, three-point bending, and Raman spectroscopy.
      Dramatic gender differences were evident in both cortical and trabecular bone
      morphological and geometric parameters. Male mice had inherently more bone and
      increased moment of inertia than genotype-matched female counterparts with
      corresponding increases in bone biomechanical strength. The primary influence of
      gender was structure/geometry in bone growth and mechanical properties, whereas
      the mineral/matrix composition and hydroxyproline content of bone were influenced
      primarily by the oim collagen mutation. This study provides evidence of the
      importance of gender in the evaluation and interpretation of potential
      therapeutic strategies when using mouse models of OI.

PMID- 23536116
TI  - Comparative properties of coordinated H2 and H2S at a ruthenium(II) centre.
AB  - Thermodynamic data for the reversible formation of cis-RuCl2(P-N)(PPh3)(eta(2)
      H2) () from trans-RuCl2(P-N)(PPh3) in C6D6 are determined by variable temperature
      (31)P{(1)H} and (1)H NMR spectroscopy; P-N = o-diphenylphosphino-N,N'
      dimethylaniline. Values of DeltaH degrees  = -26 +/- 4 kJ mol(-1), DeltaS degrees
      = -40 +/- 15 J mol(-1) K(-1), and DeltaG degrees  (at 25  degrees C) = -13.8 +/-
      0.2 kJ mol(-1) are compared with recently reported data for the corresponding H2S
      adduct (4a), where the exothermicity is greater by ~20 kJ mol(-1), but this is
      counteracted by a more unfavourable entropy change, and overall the K and DeltaG
      degrees  values at 25  degrees C are close. For loss of H2 from 2a in the solid
      state, whose X-ray structure is presented, DeltaH degrees  is 50 +/- 3 kJ mol(-1)
      as measured by Differential Scanning Calorimetry. The pKa values of the
      coordinated H2 (~11) and H2S (~14) are estimated by reactions of 2a and 4a with
      proton sponge (1,8-bis(dimethylamino)naphthalene) in CD2Cl2 at 20  degrees C; the
      mono-hydrido and -mercapto products are identified in situ. A corresponding H2O
      adduct is not deprotonated under the same conditions. Related dihydrido, mercapto
      and hydroxy species are formed by in situ reactions of 1a with NaH, NaSH, and
      NaOH, respectively.

PMID- 23536115
TI  - Oscillations of sub-membrane ATP in glucose-stimulated beta cells depend on
      negative feedback from Ca(2+).
AB  - AIMS/HYPOTHESIS: ATP links changes in glucose metabolism to electrical activity,
      Ca(2+) signalling and insulin secretion in pancreatic beta cells. There is
      evidence that beta cell metabolism oscillates, but little is known about ATP
      dynamics at the plasma membrane, where regulation of ion channels and exocytosis
      occur. METHODS: The sub-plasma-membrane ATP concentration ([ATP]pm) was recorded
      in beta cells in intact mouse and human islets using total internal reflection
      microscopy and the fluorescent reporter Perceval. RESULTS: Glucose dose
      dependently increased [ATP]pm with half-maximal and maximal effects at 5.2 and 9
      mmol/l, respectively. Additional elevations of glucose to 11 to 20 mmol/l
      promoted pronounced [ATP]pm oscillations that were synchronised between
      neighbouring beta cells. [ATP]pm increased further and the oscillations
      disappeared when voltage-dependent Ca(2+) influx was prevented. In contrast, K(+)
      depolarisation induced prompt lowering of [ATP]pm. Simultaneous recordings of
      [ATP]pm and the sub-plasma-membrane Ca(2+) concentration ([Ca(2+)]pm) during the
      early glucose-induced response revealed that the initial [ATP]pm elevation
      preceded, and was temporarily interrupted by the rise of [Ca(2+)]pm. During
      subsequent glucose-induced oscillations, the increases of [Ca(2+)]pm correlated
      with lowering of [ATP]pm. CONCLUSIONS/INTERPRETATION: In beta cells, glucose
      promotes pronounced oscillations of [ATP]pm, which depend on negative feedback
      from Ca(2+) . The bidirectional interplay between these messengers in the sub
      membrane space generates the metabolic and ionic oscillations that underlie
      pulsatile insulin secretion.

PMID- 23536117
TI  - Translating the concept of peptide labeling with 5-deoxy-5-[18F]fluororibose into
      preclinical practice: 18F-labeling of Siglec-9 peptide for PET imaging of
      inflammation.
AB  - Peptide glycosylation with 5-deoxy-5-[(18)F]fluororibose was translated into
      preclinical settings. The novel (18)F-labeled Siglec-9 peptide was produced using
      an automated synthesis procedure. The (18)F-labeled Siglec-9 peptide showed
      favorable binding in the animal model of inflammation in vivo.

PMID- 23536118
TI  - Violent extremist group ecologies under stress.
AB  - Violent extremist groups are currently making intensive use of Internet fora for
      recruitment to terrorism. These fora are under constant scrutiny by security
      agencies, private vigilante groups, and hackers, who sometimes shut them down
      with cybernetic attacks. However, there is a lack of experimental and formal
      understanding of the recruitment dynamics of online extremist fora and the effect
      of strategies to control them. Here, we utilize data on ten extremist fora that
      we collected for four years to develop a data-driven mathematical model that is
      the first attempt to measure whether (and how) these external attacks induce
      extremist fora to self-regulate. The results suggest that an increase in the
      number of groups targeted for attack causes an exponential increase in the cost
      of enforcement and an exponential decrease in its effectiveness. Thus, a policy
      to occasionally attack large groups can be very efficient for limiting violent
      output from these fora.

PMID- 23536120
TI  - Exposure to pro-smoking media in college students: does type of media channel
      differentially contribute to smoking risk?
AB  - BACKGROUND: There are almost no data on whether the different channels through
      which pro-smoking media appear (i.e., point-of-sale advertising, movie smoking)
      differently influence smoking. PURPOSE: This study used ecological momentary
      assessment to examine whether differences in smoking risk were observed for
      exposures to different pro-smoking media channels. METHODS: College students (n =
      134) carried smartphones for 21 days, recording their exposures to pro-smoking
      media and the media channels for that exposure and responding to three randomly
      issued control prompts per day. Participants answered questions about their
      future smoking risk after each pro-smoking media exposure and random prompt.
      RESULTS: Participants had elevated future smoking risk following exposure to pro
      smoking media at point of sale (p < 0.001); smoking risk at times of exposure to
      smoking in movies did not differ from risk measured during control prompts (p =
      0.78). CONCLUSIONS: There is merit to examining the relative contribution of
      different pro-smoking media channels to smoking behavior.

PMID- 23536121
TI  - Medication adherence is associated with having a caregiver among cardiac
      patients.
AB  - BACKGROUND: Medication non-adherence is a significant contributor to suboptimal
      control of blood pressure and lipids. PURPOSE: This study determined if having a
      paid and/or family caregiver was associated with medication adherence in patients
      hospitalized for cardiovascular disease. METHODS: Consecutive patients admitted
      to the cardiovascular service at a university medical center who completed a
      standardized questionnaire about medication adherence and caregiving
      (paid/professional or family member/friend) were included in this analysis (N =
      1,432; 63 % white; 63%male). RESULTS: Among cardiac patients, 39 % reported being
      prescribed >= 7 different medications, and one in four reported being non
      adherent to their medication(s). Participants who reported having/planning to
      have a paid caregiver were 40 % less likely to be non-adherent to their
      medications compared to their counterparts. The association remained significant
      after adjustment for demographic confounders and comorbid conditions (OR = 0.49;
      95 %CI = 0.29-0.82). CONCLUSION: Cardiac patients with a paid caregiver were half
      as likely to be non-adherent to medications as those without caregivers.

PMID- 23536122
TI  - Does socioeconomic status moderate the relationship between health cognitions and
      behaviors?: a comment on Conner et al.

PMID- 23536123
TI  - Small sized perylene-bisimide assemblies controlled by both cooperative and anti
      cooperative assembly processes.
AB  - Cooperative aggregation of monomers into one-dimensional nanostructures typically
      results in elongated objects. Here we analyse in depth the self-assembly of an N
      monoarylated perylene bisimide which shows characteristics of a cooperative
      growth mechanism but unexpectedly yields objects of small size, due to anti
      cooperativity by attenuated growth.

PMID- 23536124
TI  - Preventing high-risk sexual behavior in early adulthood with family interventions
      in adolescence: outcomes and developmental processes.
AB  - Adolescent study participants who engaged in a brief, family-centered
      intervention (the Family Check-Up, FCU) were later assessed for the
      intervention's effects on high-risk sexual behavior (HRSB) in early adulthood
      (age 22). Participants (N = 998 adolescents and their families) were randomly
      assigned to a family-centered intervention in sixth grade and were offered a
      gated, multilevel intervention that included (a) a school-based family resource
      center, (b) the FCU, and (c) more intensive, family-based treatment. All services
      were voluntary, but high-risk families were actively recruited into the FCU.
      Approximately 23% of the intervention families engaged in the FCU and
      approximately 18% engaged in more intensive treatment. Using an intent-to-treat
      design, we found that the direct effect of the FCU on HRSB was not significant;
      however, an analysis of the developmental processes indicated that intervention
      families demonstrated improved family relationship quality when compared to
      control families, which in turn resulted in lower levels of HRSB in early
      adulthood. Furthermore, the significant effect of family relationship quality on
      HRSB was mediated by differences in parental monitoring and early sexual
      activity, and these effects varied as a function of gender and ethnicity.
      Indirect effects of the FCU on HRSB were significant via multiple different
      pathways. The implications of these findings for enhancing the impact of family
      centered interventions are discussed.

PMID- 23536125
TI  - Stability and bioactivity of a Bowman-Birk inhibitor in orange juice during
      processing and storage.
AB  - The present research aimed to evaluate the feasibility of a soybean Bowman-Birk
      inhibitor (BBI) as a natural functional food ingredient. The influence of food
      processing, storage and digestion on the structure and bioactivity of BBI added
      to a food matrix was evaluated. The cytotoxic effect of the digested samples was
      also tested with the aim to provide information regarding the safe use of BBI as
      a functional food ingredient. Samples of freshly squeezed orange juice (OJ) and
      two orange juice model systems (OJ-ms) supplemented and non-supplemented with BBI
      were prepared and processed mimicking pasteurization and sterilization industrial
      conditions. Moreover, pasteurized samples were stored at 4  degrees C for two
      months. The samples were digested in vitro under oral-gastrointestinal
      physiological conditions. Results seem to indicate that the activity of BBI
      supplemented to the food matrix sufficiently survives thermal processing, storage
      and digestion processes. Changes in BBI bioactivity may be ascribed among others
      to the Maillard reaction. Formation of early Maillard reaction products also
      called Amadori products has been detected in the food sample. No cytotoxic effect
      was observed for the samples under study. In conclusion, our findings support
      that BBI has significant potential as a natural functional food ingredient in
      pasteurized orange juice stored at 4  degrees C. 

PMID- 23536126
TI  - Metal-free aerobic oxidation of benzazole derivatives.
AB  - 2-Benzyl benzothiazoles and benzimidazoles are easily oxidized under air and
      basic conditions to give the corresponding ketones in good yields. The use of
      palladium acetate as a catalyst has little effect and even gives, in some cases,
      much lower yields.

PMID- 23536127
TI  - Animal models in obesity and hypertension.
AB  - Although obesity is a well-known risk factor for hypertension, the mechanisms by
      which hypertension develops in obese patients are not entirely clear. Animal
      models of obesity and their different susceptibilities to develop hypertension
      have revealed some of the mechanisms linking obesity and hypertension. Adipose
      tissue is an endocrine organ secreting hormones that impact blood pressure, such
      as elements of the renin-angiotensin system whose role in hypertension have been
      established. In addition, the appetite-suppressing adipokine leptin activates the
      sympathetic nervous system via the melanocortin system, and this activation,
      especially in the kidney, increases blood pressure. Leptin secretion from
      adipocytes is increased in most models of obesity due to leptin resistance,
      although the resistance is often selective to the anorexigenic effect, while the
      susceptibility to the hypertensive effect remains intact. Understanding the
      pathways by which obesity contributes to increased blood pressure will hopefully
      pave the way to and better define the appropriate treatment for obesity-induced
      hypertension.

PMID- 23536128
TI  - High blood pressure: the leading global burden of disease risk factor and the
      need for worldwide prevention programs.

PMID- 23536130
TI  - The role of Oxalobacter formigenes colonization in calcium oxalate stone disease.
AB  - About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram
      negative anaerobic bacterium that degrades oxalate in the intestinal tract, we
      assessed the role of O. formigenes in oxalate metabolism by evaluating its
      intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium
      oxalate stone formers, 26 tested negative for O. formigenes and were compared
      with the 11 patients who tested positive. Patients provided 24-h urine samples on
      both a self-selected and a standardized diet. Urinary oxalate excretion did not
      differ significantly on the self-selected diet, but was significantly lower in O.
      formigenes-positive than in O. formigenes-negative patients under controlled,
      standardized conditions. Intestinal oxalate absorption, measured using
      [(13)C2]oxalate, was similar in the patients with or without O. formigenes.
      Plasma oxalate concentrations were significantly higher in noncolonized (5.79
      MUmol/l) than in colonized stone formers (1.70 MUmol/l). Colonization with O.
      formigenes was significantly inversely associated with the number of stone
      episodes. Our findings suggest that O. formigenes lowers the intestinal
      concentration of oxalate available for absorption at constant rates, resulting in
      decreased urinary oxalate excretion. Thus, dietary factors have an important role
      in urinary oxalate excretion. The data indicate that O. formigenes colonization
      may reduce the risk of stone recurrence.

PMID- 23536129
TI  - Ambulatory blood pressure monitoring in the prediction and prevention of coronary
      heart disease.
AB  - We reviewed studies of ambulatory blood pressure monitoring (ABPM) in patients
      with symptomatic coronary heart disease (CHD) or asymptomatic coronary lesions
      and in patients at high coronary risk, such as in the presence of hypertension.
      We identified ten cross-sectional and seven prospective studies in patients with
      CHD or coronary lesions. These studies showed that patients with CHD or coronary
      lesions often had nocturnal non-dipping or increased blood pressure variability,
      and might have increased risk of coronary events, due to either uncontrolled
      hypertension or treatment-induced hypotension identified by ABPM. We identified
      ten observational studies in hypertensive patients and normotensive subjects and
      five therapeutic trials in hypertension. These observational studies demonstrated
      that one or more ambulatory blood pressure components might provide predictive
      value for coronary events above and beyond clinic blood pressure. The therapeutic
      trials were less conclusive, but suggestive of additional value for the
      prevention of coronary events.

PMID- 23536131
TI  - Heterozygous non-synonymous ROBO2 variants are unlikely to be sufficient to cause
      familial vesicoureteric reflux.
AB  - ROBO2, the receptor of SLIT2, is one of many genes/proteins that regulate the
      outgrowth of the ureteric bud, which is the first step in the development of the
      metanephric urinary system. Non-synonymous variants in ROBO2 have been found in a
      small proportion of patients with primary vesicoureteric reflux (VUR) in various
      countries. Here we sequenced 1 kb of promoter and all exons of ROBO2b with
      intronic margins in 227 index cases with primary VUR in an Irish population and
      found 55 variants, of which 20 were novel. We assessed the variants for
      evolutionary conservation and investigated novel and uncommon known conserved
      variants in 23 further index cases and family members of all index cases (to
      check for segregation with VUR), and then in healthy controls if we found
      segregation of the variants with VUR. Apart from one non-synonymous variant that
      was previously found in controls, we did not find any of the six other previously
      reported non-synonymous variants, but found four new non-synonymous variants. Of
      those, only two segregated with the disorder (p.Pro522Thr and p.Val799Ile). The
      former was not present in any of 592 healthy controls; the latter was present in
      one control. There are now 35 reported non-synonymous coding variants of ROBO2b.
      The predicted pathogenicity of those that have so far been found exclusively in
      VUR patients does not differ from that predicted for those variants also found in
      controls. Thus, our finding does not completely rule out that some variants may
      be the sole cause of VUR, but it is clear from the overall frequency that most of
      them cannot be. However, it is possible that some of these variants may cause VUR
      in combination with a mutation in another gene.

PMID- 23536132
TI  - Audit-based education lowers systolic blood pressure in chronic kidney disease:
      the Quality Improvement in CKD (QICKD) trial results.
AB  - Strict control of systolic blood pressure is known to slow progression of chronic
      kidney disease (CKD). Here we compared audit-based education (ABE) to guidelines
      and prompts or usual practice in lowering systolic blood pressure in people with
      CKD. This 2-year cluster randomized trial included 93 volunteer general practices
      randomized into three arms with 30 ABE practices, 32 with guidelines and prompts,
      and 31 usual practices. An intervention effect on the primary outcome, systolic
      blood pressure, was calculated using a multilevel model to predict changes after
      the intervention. The prevalence of CKD was 7.29% (41,183 of 565,016 patients)
      with all cardiovascular comorbidities more common in those with CKD. Our models
      showed that the systolic blood pressure was significantly lowered by 2.41 mm Hg
      (CI 0.59-4.29 mm Hg), in the ABE practices with an odds ratio of achieving at
      least a 5 mm Hg reduction in systolic blood pressure of 1.24 (CI 1.05-1.45).
      Practices exposed to guidelines and prompts produced no significant change
      compared to usual practice. Male gender, ABE, ischemic heart disease, and
      congestive heart failure were independently associated with a greater lowering of
      systolic blood pressure but the converse applied to hypertension and age over 75
      years. There were no reports of harm. Thus, individuals receiving ABE are more
      likely to achieve a lower blood pressure than those receiving only usual
      practice. The findings should be interpreted with caution due to the wide
      confidence intervals. 

PMID- 23536133
TI  - Urine haptoglobin levels predict early renal functional decline in patients with
      type 2 diabetes.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary
      albumin to creatinine ratio is used as a predictor for the development of
      nephropathy but it is neither sensitive nor specific. Here we used liquid
      chromatography/mass spectrometry on urine of eight normoalbuminuric patients with
      type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss
      of renal function. Initial verification of seven markers (agrin, haptoglobin,
      mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and
      uromodulin) in the urine of an additional 30 patients showed that haptoglobin was
      the best predictor of early renal functional decline. We then measured this in
      the urine of 204 patients with type 2 diabetes who did not yet have significant
      kidney disease (estimated glomerular filtration rate stage 2 or better and an
      albumin to creatinine ratio <300 mg/g). In comparing the highest to lowest
      tertiles, the odds ratio for having early renal function decline was 2.70 (CI:
      1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI
      1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment
      group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio
      to a model using the albumin to creatinine ratio to predict early renal function
      decline resulted in improved predictive performance. Thus, the haptoglobin to
      creatinine ratio may be useful to predict patients with type 2 diabetes at risk
      of nephropathy before the development of macroalbuminuria or reduced glomerular
      filtration rate.

PMID- 23536135
TI  - The anisotropic nature of the human vocal fold: an ex vivo study.
AB  - The purpose of this study was to measure the relationship between the shear
      elastic properties of vocal fold with respect to the direction of applied stress.
      There is extensive published material that quantifies the shear viscoelastic
      properties of the vocal fold, but as much of these data were obtained using
      rotating parallel plate rheometers, which are unable to resolve out difference of
      the shear elastic behaviour with respect to direction, there is very little data
      that indicates anisotropic behaviour. To overcome this gap in knowledge, the team
      devised an apparatus that is capable of applying a shear stress in a known
      direction. A series of measurements were taken at the mid-membranous position, in
      the transverse and longitudinal directions. Point-specific measurements were
      performed using fourteen human cadaver excised larynges, which were hemi
      sectioned to expose the vocal fold. An extremely low sinusoidal shear force of 1
      g was applied tangentially to the membrane surface in both the longitudinal and
      transverse direction, and the resultant shear strain was measured. With the probe
      applied to the intact vocal fold, the average ratio of the elasticity in the
      transverse with respect to the longitudinal direction was 0.55. Further
      investigation using histological staining of collagens in the lamina propria
      indicates that there is a visible difference in the general alignment of collagen
      fibres when comparing the coronal and the sagittal sections. Our conclusion is
      that there is a quantifiable difference between the shear elastic response of the
      lamina propria in the longitudinal and transverse directions, and that this could
      be explained by the difference in alignment of collagen fibres within the lamina
      propria.

PMID- 23536134
TI  - Polygenic risk and the developmental progression to heavy, persistent smoking and
      nicotine dependence: evidence from a 4-decade longitudinal study.
AB  - IMPORTANCE: Genome-wide hypothesis-free discovery methods have identified loci
      that are associated with heavy smoking in adulthood. Research is needed to
      understand developmental processes that link newly discovered genetic risks with
      adult heavy smoking. OBJECTIVE: To test how genetic risks discovered in genome
      wide association studies of adult smoking influence the developmental progression
      of smoking behavior from initiation through conversion to daily smoking,
      progression to heavy smoking, nicotine dependence, and struggles with cessation.
      DESIGN: A 38-year, prospective, longitudinal study of a representative birth
      cohort. SETTING: The Dunedin Multidisciplinary Health and Development Study of
      New Zealand. PARTICIPANTS: The study included 1037 male and female participants.
      EXPOSURE: We assessed genetic risk with a multilocus genetic risk score. The
      genetic risk score was composed of single-nucleotide polymorphisms identified in
      3 meta-analyses of genome-wide association studies of smoking quantity
      phenotypes. MAIN OUTCOMES AND MEASURES: Smoking initiation, conversion to daily
      smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of
      Nicotine Dependence), and cessation difficulties were evaluated at 8 assessments
      spanning the ages of 11 to 38 years. RESULTS: Genetic risk score was unrelated to
      smoking initiation. However, individuals at higher genetic risk were more likely
      to convert to daily smoking as teenagers, progressed more rapidly from smoking
      initiation to heavy smoking, persisted longer in smoking heavily, developed
      nicotine dependence more frequently, were more reliant on smoking to cope with
      stress, and were more likely to fail in their cessation attempts. Further
      analysis revealed that 2 adolescent developmental phenotypes-early conversion to
      daily smoking and rapid progression to heavy smoking-mediated associations
      between the genetic risk score and mature phenotypes of persistent heavy smoking,
      nicotine dependence, and cessation failure. The genetic risk score predicted
      smoking risk over and above family history. CONCLUSIONS AND RELEVANCE:
      Initiatives that disrupt the developmental progression of smoking behavior among
      adolescents may mitigate genetic risks for developing adult smoking problems.
      Future genetic research may maximize discovery potential by focusing on smoking
      behavior soon after smoking initiation and by studying young smokers.

PMID- 23536136
TI  - Reliability of cone beam computed tomography in scalar localization of the
      electrode array: a radio histological study.
AB  - Postoperative imaging plays a growing role in clinical studies concerning
      prognostic factors in cochlear implantation. Indeed, intracochlear position of
      the cochlear implant has recently been identified as a contributor in functional
      outcomes and radiological tools must be accurate enough to determine the final
      placement of the electrode array. The aim of our study was to validate cone beam
      computed tomography as a reliable technique for scalar localization of the
      electrode array. We performed therefore a temporal bone study on ten specimens
      that were implanted with a perimodiolar implant prototype. Cone beam
      reconstructions were performed and images were analyzed by two physicians both
      experienced in cochlear implant imaging, who determined the scalar localization
      of the implant. Temporal bones then underwent histological control to document
      this scalar localization and hypothetical intracochlear lesions. In four cases, a
      dislocation from scala tympani to scala vestibuli was suspected on cone beam
      reconstructions of the ascending part of the basal turn. In three of these four
      specimens, dislocation in pars ascendens was confirmed histologically. In the
      remaining temporal bone, histological analysis revealed an elevation with rupture
      of the basilar membrane. Histological assessment revealed spiral ligament tearing
      in another bone. We conclude that cone beam is a reliable tool to assess scalar
      localization of the selectrode array and may be used in future clinical studies. 

PMID- 23536138
TI  - A multidisciplinary audit of head and neck referrals: considerations for
      patients' timelines and outcomes.
AB  - The Rapid Diagnostic Clinic (RDC) was introduced to comply with NICE
      recommendations for improving head and neck cancer services (National Institute
      of Clinical Excellence 2004 Improving outcomes in head and neck cancer: the
      manual. NICE, London). It provides multi-modality specialist assessment for new
      referrals, with on-site sonography and cytology. We have critically appraised the
      efficacy of our RDC, with respect to its impact on patients' timelines and
      outcomes. A retrospective audit of new referrals to the head and neck clinic
      during a 6-month period was conducted (pre-RDC period); areas in delay in
      patients reaching a definitive outcome were identified. Following implementation
      of the RDC, a second cycle, prospective audit was performed and its impact on
      timelines for patients' journey and outcomes determined. One hundred and ninety
      seven patients were seen during the pre-RDC period. The average time from
      referral to being seen was 11 days for 2-week wait (2WW) referrals and 34 days
      for other sources. During the RDC period, 299 patients were seen in total. The
      average waiting time was reduced to 9 days for 2WW referrals and 23 days for
      other referrals. During the RDC period, over one-third of patients utilised the
      provision of ultrasound +/- FNAC, and consequently, the majority reached a
      definitive outcome (discharged or scheduled for surgery) following their first
      consultation. This was a significant improvement compared to the pre-RDC period,
      where the main outcome was referral for an investigation, with consequently
      longer waiting time for surgery. We report the first study to consider the effect
      of a 'one-stop' clinic on patients' journey timelines and outcomes. Our study has
      shown that the RDC provides an efficient and effective system, which facilitates
      the patients' pathway to a definitive management plan.

PMID- 23536137
TI  - The prevalence of allergic fungal rhinosinusitis in sinonasal polyposis.
AB  - Allergic fungal sinusitis (AFS) is a noninvasive form of fungal rhinosinusitis
      with a prevalence of 6-9 % among all rhinosinusitis cases requiring surgery. The
      fungi causing AFRS have a great diversity and regional variation in the incidence
      of AFS has been reported worldwide. The aim of this study was to evaluate the
      prevalence of AFS among rhinosinusitis patients in the north east of Iran. In a
      prospective cross-sectional study 127 patients with sinonasal polyposis who were
      candidates for surgery were recruited. All cases were evaluated by sinonasal CT
      scan, Prick test for common regional allergens, total serum immunoglobulin E
      (IgE) level, and allergic mucin culture for fungi in suspected cases. Data
      analyses were done using SPSS version 13.0. Their mean age was 37.4 +/- 11.6
      years, the male-to-female ratio was 69/58. Eleven patients (9.45 %) met the AFS
      criteria. Nine cases had a positive culture for Aspergillus specimen and three
      for Alternaria. Prick test was positive for at least one allergen in 28 cases
      (22.05 %). The most common allergen was weed. The total IgE level was
      significantly higher in AFS patients. This study showed the prevalence of AFS
      among patients with nasal polyposis to be 9.45 %.

PMID- 23536139
TI  - Factors associated with a willingness to accept rapid HIV testing in an urban
      emergency department.
AB  - Emergency Departments (EDs) provide primary healthcare to many underserved
      persons without access to preventive healthcare elsewhere. We conducted a cross
      sectional study to test the hypothesis that patients are more likely to express a
      willingness to accept rapid HIV testing in the ED if they lack access to
      preventive healthcare elsewhere. Medicaid insurance, younger age, lack of a usual
      place of healthcare, high perceived HIV risk, and actual HIV risk were associated
      with increased HIV test acceptance. These results support the need for and
      acceptability of rapid HIV testing in the ED particularly for individuals who may
      lack access to this preventive healthcare screening elsewhere. 

PMID- 23536140
TI  - Rapid HIV testing for individuals on probation/parole: outcomes of an
      intervention trial.
AB  - Many probationers and parolees do not receive HIV testing despite being at
      increased risk for obtaining and transmitting HIV. A two-group randomized
      controlled trial was conducted between April, 2011 and May, 2012 at
      probation/parole offices in Baltimore, Maryland and Providence/Pawtucket, Rhode
      Island. Male and female probationers/parolees were interviewed (n = 1,263) and
      then offered HIV testing based on random assignment to one of two conditions: (1)
      On-site rapid HIV testing conducted at the probation/parole office; or (2)
      Referral for rapid HIV testing off site at a community HIV testing clinic.
      Outcomes were: (1) undergoing HIV testing; and (2) receipt of HIV testing
      results. Participants were significantly more likely to be tested on-site at a
      probation/parole office versus off-site at a HIV testing clinic (p < 0.001).
      There was no difference between the two groups in terms of receiving HIV testing
      results. Findings indicate that probationers/parolees are willing to be tested on
      site and, independent of testing location, are equally willing to receive their
      results. Implications for expanding rapid HIV testing to more criminal justice
      related locations and populations are discussed.

PMID- 23536142
TI  - Axially chiral monomeric and dimeric square planar Pd(II) complexes and their
      application to chiral tectonics.
AB  - Mononuclear and dinuclear square planar palladium(II) complexes (denoted by
      [(hfac)Pd(II)(L-LH)] and [(hfac)Pd(II)(L-L)Pd(II)(hfac)], respectively) were
      synthesized. Here hfac(-), HL-L(-) and L-L(2-) denote hexafluoroacetylacetonato,
      monoprotonated and non-protonated bis-beta-diketonato ligands, respectively.
      Three bis-beta-diketones were used as HL-LH: 1,2-diacetyl-1,2-dibenzoylethane
      (denoted by dabeH2), 1,2-diacetyl-1,2-bis(3-methylbutanoyl)ethane (baetH2) and
      1,2-diacetyl-1,2-propanoylethane (dpeH2). Both the monomeric and dimeric Pd(II)
      complexes were chiral due to the orthogonal twisting of the two non-symmetric
      diketonato moieties in HL-L(-) and L-L(2-), respectively. Optical resolution of
      [(hfac)Pd(II)(dabe)Pd(II)(hfac)] was achieved chromatographically on a chiral
      column to obtain a pair of optical antipodes which were stable against
      racemization. As for the other complexes, resolution was possible only after
      replacing hfac(-) with a bulky ligand such as dibenzoylmethanato (dbm(-)).
      Although a dinuclear complex with a symmetric bis-beta-diketonato ligand,
      [(hfac)Pd(II)(taet)Pd(II)(hfac)] (taet(2-) = 1,1,2,2-tetraacetylethanato), was
      achiral, the replacement of the terminal ligands with non-symmetric beta
      diketonates yielded an axially chiral complex such as
      [(phacac)Pd(II)(taet)Pd(II)(phacac)], wherein phacac(-) denotes 1-phenyl-1,3
      butanedionato. The UV and CD spectra of the Pd(II) complexes were analyzed with
      the help of the TDDFT calculations. The chiral monomeric species, [(dbm)Pd(II)(R-
      or S-baetH)], formed a heterometallic tetranuclear complex,
      [Fe(III){(dbm)Pd(II)(R- or S-baet)}3], in methanol solution.

PMID- 23536141
TI  - Effects of household shocks and poverty on the timing of traditional male
      circumcision and HIV risk in South Africa.
AB  - Poverty may influence HIV risk by increasing vulnerability to economic shocks and
      thereby preventing key health investments. We explored this possibility by
      examining the relationship between household shocks and the timing of traditional
      male circumcision, a practice associated with considerable expense and whose HIV
      prevention benefits are larger when done earlier, even within young adulthood.
      Using unique data on a sample of Xhosa men, a group that almost universally
      practices traditional circumcision, we found that respondents in the poorest
      households delayed circumcision by 2 years if a household member experienced loss
      of income or death and/or illness. The impact of these shocks declined with
      increasing household income. Our findings suggest that interventions that work to
      mitigate the impact of shocks among the poor may be useful in HIV prevention
      efforts. More generally, they illustrate that the relationship between HIV and
      wealth may be more nuanced than assumed in previous work.

PMID- 23536143
TI  - Relationship dissatisfaction and other risk factors for future relationship
      dissolution: a population-based study of 18,523 couples.
AB  - PURPOSE: There has been a marked increase in divorce rates in most Western
      societies over the last 50 years. Relationship dissolution is associated with
      negative consequences both for adults and children, so it is important to
      understand the factors that help retain marital stability. The first aim of this
      prospective study was to identify risk factors for relationship dissolution in
      18,523 couples in Norway, with a particular focus on individual dissatisfaction
      with the relationship. The second aim was to assess interaction effects between
      relationship dissatisfaction and other predictors of relationship dissolution.
      METHODS: Pregnant women and their partners enrolled in the Norwegian Mother and
      Child Cohort study completed questionnaires during the pregnancy that asked about
      relationship dissatisfaction, strain, demographics, and other risk factors. The
      main outcome variable was relationship dissolution in the 39-month period from
      gestational week 30-36 months postpartum. Associations between the risk factors
      and relationship dissolution were estimated by logistic regression analysis.
      RESULTS: Except for younger female age, relationship dissatisfaction in women and
      lower education in men, were the strongest predictors of relationship
      dissolution. Another strong factor was women's persistent strain. No significant
      interaction effects were found between relationship dissatisfaction and the other
      variables in the analyses. CONCLUSIONS: Dissatisfaction with the relationship, in
      particular in women, and low male education are important predictors of
      relationship dissolution, although other factors are also related to dissolution.
      There are only few studies on relationship predictors of dissolution conducted in
      Europe, and the current study adds to this body of knowledge.

PMID- 23536145
TI  - Thoracoscopy-assisted removal of a thoracoamniotic shunt double-basket catheter
      dislodged into the fetal thoracic cavity: report of three cases.
AB  - The indications for and timing of surgical removal of a dislodged thoracoamniotic
      shunt double-basket catheter are not established, and the side effects of the
      dislodged into the thoracic cavity remain controversial. The double-basket
      catheter was designed to reduce the incidence of catheter dislodgement; however,
      we have encountered four cases of thoracoamniotic shunt double-basket catheter
      dislodgement into the fetal thorax. The dislodged shunt catheters were removed
      safely with thoracoscopic assistance within several days of birth, when
      additional treatments for pleural effusion were needed, such as thoracic drainage
      tube insertion and adhesion treatment of the thorax. We report the clinical
      courses of three of these cases of thoracoamniotic shunt tube dislocation. By
      waiting several days postnatally for stabilization of respiratory and circulatory
      status and the effective use of thoracoscopic assistance, the dislodged catheter
      was safely removed from the neonatal thorax. The accumulation of case reports
      will help establish suitable treatments, and their indication, for a dislodged
      thoracoamniotic shunt catheter within the fetal thoracic cavity. 

PMID- 23536146
TI  - A giant metallo-supramolecular cage encapsulating a single-molecule magnet.
AB  - A giant metallo-supramolecular cage encapsulating a single-molecule magnet,
      [Ag42{Ho(W5O18)2}(t-BuC=C)28Cl4]OH, is prepared and structurally characterized.
      It shows an interesting "peanut-like" structure and remains intact in solution as
      demonstrated by NMR studies.

PMID- 23536147
TI  - Facile degradation of benzenediazonium-grafted thick layers on the electrode
      surface enabling electrochemical biosensor application.
AB  - We found that the formylbenzenediazonium (FBD)-grafted organic layers can be
      degraded by treating with an aqueous solution of salt and Tween. An
      electrochemical immunoassay was carried out on the degraded surface, which
      allowed highly sensitive detection of antigen mouse IgG.

PMID- 23536149
TI  - Cu/Ba/bauxite: an inexpensive and efficient alternative for Pt/Ba/Al2O3 in NOx
      removal.
AB  - Cu/Ba/bauxite possesses superior NOx storage and reduction (NSR) performances,
      high thermal stability, strong resistance against SO2 poisoning and outstanding
      regeneration ability in comparison with Pt/Ba/Al2O3. It can serve as a cheap and
      promising alternative for traditional Pt/Ba/Al2O3 in NOx removal from lean-burn
      engines.

PMID- 23536148
TI  - Thienopyrrole-expanded BODIPY as a potential NIR photosensitizer for photodynamic
      therapy.
AB  - The synthesis and characterization of a highly photostable bromo-substituted
      BODIPY dye (I) fused-ring-expanded with thienopyrrole moieties is reported. The
      results of MTT assays and flow cytometric analyses in living HeLa cells
      demonstrate that I has a high singlet oxygen quantum yield (PhiDelta = 0.63) and
      exhibits photocytotoxicity upon irradiation in the NIR region making it
      potentially suitable for use in PDT.

PMID- 23536150
TI  - Association study between FSHR Ala307Thr and Ser680Asn variants and polycystic
      ovary syndrome (PCOS) in Northern Chinese Han women.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common complex genetic
      endocrinopathy. It has high heritability, and twin studies indicate that it is a
      complex polygenic disorder. Searching for major genes of PCOS is crucial to
      clarify its molecular pathogenesis. A previous genome-wide association study in
      Chinese women with PCOS identified a region on chromosome 2p16.3 that encodes the
      follicle-stimulating hormone receptor (FSHR) genes as a reproducible PCOS
      susceptibility locus. In the present study, we performed a replication analysis
      of the association between two common variants of the FSHR gene and PCOS in
      Northern Chinese Han women. RESULTS: We recruited 384 unrelated PCOS patients and
      768 healthy individuals from the Shaanxi province in the northern part of China.
      Two polymorphisms (Ala307Thr and Ser680Asn) of the FSHR gene and the clinical
      characteristics of the study subjects were analyzed in the case-control sample.
      The frequency of FSHR Ala307Thr and Ser680Asn variants along with the haplotype
      was not significantly different between the PCOS patients and the controls;
      however, the Ser680 variants may be associated with high levels of FSH and low E2
      levels. CONCLUSION: The variant of Ser680 was not associated with PCOS but it may
      be related to high FSH levels. The present study suggests that the two variants
      of the FSHR gene are not a causative factor of PCOS in Northern Chinese Han
      women.

PMID- 23536151
TI  - What is the best treatment option for infertile women aged 40 and over?
AB  - PURPOSE: To summarise the causes of decreased fecundity with age and review
      chronological vs biological ovarian ageing. To explore the clinician's means of
      assessing a woman's ovarian reserve. To review the recent literature on the
      effectiveness of different assisted reproductive technology (ART) techniques for
      women aged 40 and over and offer a single best treatment option. METHODS: Pubmed
      and google scholar were searched for relevant articles using key words. Data were
      extracted based on authors, year, aims, sample and results. RESULTS: Success
      rates for women aged 40 or over with clomiphene, IUI, IUI with FSH are all
      extremely low, at less than 1% live birth per cycle. However, IVF offers a
      success rate of around 13.7% per cycle. CONCLUSION: An exploration of the
      effectiveness of available treatment options for older infertile women using
      their own gametes suggests that IVF offers the best prospects of success.
      Attempting treatments other than IVF will delay conception unnecessarily.

PMID- 23536152
TI  - Astaxanthin ameliorates heat stress-induced impairment of blastocyst development
      in vitro:--astaxanthin colocalization with and action on mitochondria--.
AB  - PURPOSE: The effects of astaxanthin (Ax) on the in vitro development of bovine
      embryos cultured under heat stress were investigated in combination with the
      assessment of its cellular accumulation and action on mitochondrial membrane
      potential (DeltaPsim). METHODS: Bovine >=8-cell embryos were collected on day 3
      after in vitro fertilization and exposed to single (day 4) or repeated (day 4 and
      5) heat stress (10 h/day at 40.5  degrees C). Ax was added into culture medium
      under the repeated heat stress and blastocyst development was evaluated. The
      cellular uptake of Ax in embryos was examined using bright-field and confocal
      laser-scanning microscopy, and high-performance liquid chromatography. The
      relationship between Ax and mitochondria localization was assessed using
      MitoTracker dye. The effects of Ax on DeltaPsim were investigated using JC-1 dye.
      RESULTS: Blastocyst development in the repeated heat stress treatment decreased
      significantly (P < 0.05) compared with those in single heat stress or normal
      thermal treatment. The addition of Ax into culture medium did lead to a
      significant recovery in blastocyst development in the repeated heat-treated
      group. Ax was detected in cytoplasm of embryos and observed to colocalize with
      mitochondria. Ax recovered DeltaPsim in embryos that was decreased by the heat
      treatment. CONCLUSIONS: Ax ameliorated the heat stress-induced impairment of
      blastocyst development. Our results suggest that the direct action of Ax on
      mitochondrial activity via cellular uptake is a mechanism of the ameliorating
      effects.

PMID- 23536153
TI  - Thoracic duct relationships to abnormal neurovascular structures in
      cervicothoracic regions: case study and clinical relevance.
AB  - The presence of variant intercostal and bronchial arteries and variable position
      of left recurrent laryngeal nerve (LRLN) along the course of thoracic duct (TD)
      may have clinical relevance in various cervicothoracic surgeries. 

PMID- 23536155
TI  - Functional imaging in chronic migraine.
AB  - Chronic migraine is a relatively common disorder in neurological terms that
      causes very significant disability at a high cost. The precise mechanisms behind
      the progression of episodic migraine to chronic migraine are not well understood.
      Functional neuro-imaging works on the basis that neuronal activations are
      associated with changes in regional cerebral blood flow, and it can help us
      answer some of these questions. In this review, we discuss important recent
      studies in chronic migraine or studies relating to increasing frequency of
      migraine attacks. The findings show that increasing frequency of migraine attacks
      is associated with changes in key brainstem areas, basal ganglia and various
      cortical areas involved in pain.

PMID- 23536157
TI  - Formation and distribution of 2,4-dihydroxy-2,5-dimethyl-3(2H)-thiophenone, a
      pigment, an aroma and a biologically active compound formed by the Maillard
      reaction, in foods and beverages.
AB  - We recently identified 2,4-dihydroxy-2,5-dimethyl-3(2H)-thiophenone (DHDMT) from
      soy sauce as a low-molecular-weight pigment formed by the Maillard reaction.
      DHDMT has also been reported as an aroma compound in a model system and a
      biologically active compound of heated garlic. To utilize these functions
      efficiently, we here examined how DHDMT was formed during fermentation of soy
      sauce and in model systems. Although DHDMT was formed from cysteine and glucose,
      it was formed more from cystine and fructose in the model system. We also showed
      that this compound exists in various kinds of soy sauce and miso as well as in
      some brown foods and beverages such as roasted bread and beer. 

PMID- 23536158
TI  - In situ preparation of highly fluorescent pyrene-dyes from non-luminous
      precursors upon photoirradiation.
AB  - The non-luminous precursor, 2-(1-pyrenyl)-9,10-dihydro-9,10-ethanoanthracene
      11,12-dione, was photochemically converted to highly-fluorescent 2-(1
      pyrenyl)anthracene quantitatively in solution and in the PMMA film and the
      fluorescence quantum yield of the acene in benzonitrile was as high as 0.99.

PMID- 23536160
TI  - The development of a one pot, regiocontrolled, three-component reaction for the
      synthesis of thieno[2,3-c]pyrroles.
AB  - A three-component reaction has been developed that allows the regioselective
      synthesis of thieno[2,3-c]pyrroles. The reaction is based on the ability of 2
      acetyl-3-thiophenecarboxaldehyde to react with amine and thiol nucleophiles to
      produce the corresponding tri-substituted thieno[2,3-c]pyrroles, with water as
      the only by-product. The developed reaction expands the range of synthetically
      accessible, tri-substituted thieno[2,3-c]pyrroles.

PMID- 23536161
TI  - alpha-Lipoic acid ameliorates mitochondrial impairment and reverses apoptosis in
      FABP3-overexpressing embryonic cancer cells.
AB  - Fatty acid-binding protein 3 (FABP3) is a low molecular weight protein with
      distinct tissue distribution, which may play an important role in fatty acid
      transport, cell growth, cellular signaling, and gene transcription. We have
      previously shown FABP3 was more highly expressed in myocardium with ventricular
      septal defects than in normal myocardium and furthermore, that overexpression of
      FABP3 causes mitochondrial dysfunction and induces apoptosis in the P19 mouse
      teratocarcinoma cell line (P19), which is a suitable model for the investigation
      of cardiac differentiation at the molecular and functional levels. alpha-Lipoic
      acid (alpha-LA), a natural dithiol compound with antioxidant properties, has been
      reported to protect mitochondrial function in cells. In this study, we
      established an FABP3-overexpressing P19 cell line for the investigation of the
      impact of alpha-LA on mitochondrial impairment and apoptosis in these cells.
      Mitochondrial morphology was evaluated by transmission electron microscopy, while
      the effects of alpha-LA on reactive oxygen species (ROS) production,
      mitochondrial membrane potential (MMP), intracellular ATP content and the amount
      of mitochondrial DNA were analyzed by flow cytometry, a commercially available
      assay and quantitative real-time PCR, respectively. The results revealed that
      alpha-LA ameliorated mitochondrial deformation and decreased intracellular ROS
      production. Furthermore, the MMP, intracellular ATP synthesis and the amount of
      mitochondrial DNA were also increased. Most significantly, alpha-LA was shown to
      reverse apoptosis. Collectively, our results indicate that abnormalities in FABP3
      expression contribute to mitochondrial dysfunction and apoptosis, and that alpha
      LA represents a suitable candidate for development as a treatment for apoptosis
      related congenital cardiac malformations. 

PMID- 23536163
TI  - Efficacy and safety of ixabepilone in taxane-resistant patients with metastatic
      breast cancer previously treated with anthracyclines: results of a phase II study
      in Japan.
AB  - PURPOSE: Anthracycline and taxane resistance is a key issue in the treatment of
      metastatic breast cancer (MBC), particularly in Asian patients who often present
      with advanced disease. The objective of this study was to investigate the
      efficacy and safety of ixabepilone monotherapy in Japanese patients with taxane
      resistant MBC previously treated with anthracycline. PATIENTS AND METHODS:
      Japanese patients with taxane-resistant MBC previously treated with anthracycline
      were treated with 40 mg/m(2) ixabepilone every 3 weeks. Primary endpoint was
      overall response rate. Secondary endpoints included duration of response, time to
      progression (TTP), and safety. RESULTS: Fifty-two patients were treated with
      ixabepilone. Overall response rate was 11.5 % (95 % confidence interval 4.4
      23.4), stable disease rate was 38.5 %, duration of response was 3.6 months (range
      2.4-5.3 months), and TTP was 2.8 months (range 0.7-8.1 months). The most frequent
      grade 3/4 toxicities were neutropenia (82.7 %), leukopenia (75 %), myalgia (19.2
      %), and peripheral neuropathy (19.2 %). CONCLUSION: Ixabepilone monotherapy was
      effective and toxicities were manageable in this phase II study of Japanese
      patients with taxane-resistant metastatic breast cancer previously treated with
      anthracyclines.

PMID- 23536162
TI  - Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7
      cells.
AB  - Bax, a pro-apoptotic member of the Bcl-2 family of proteins has the ability to
      form transmembrane pores large enough to allow cytochrome c (Cyt c) release, as
      well as to activate the mitochondrial permeability transition pore (mPTP);
      however, no differential study has been conducted to clarify which one of these
      mechanisms predominates over the other in the same system. In the present study,
      we treated isolated mitochondria from MCF7 cells with recombinant protein Bax and
      tested the efficacy of the mPTP inhibitor cyclosporin A (CsA) and of the Bax
      channel blocker (Bcb) to inhibit cytochrome c release. We also, induced apoptosis
      in MCF7 cell cultures with TNF-alpha plus cycloheximide to determine the effect
      of such compounds in apoptosis induction via mPTP or Bax oligomerization.
      Cytochrome c release was totally prevented by CsA and partially by Bcb when
      apoptosis was induced with recombinant Bax in isolated mitochondria from MCF7
      cells. CsA increased the number of living cells in cell culture, as compared with
      the effect of Bax channel blocker. These results indicate that mPTP activation is
      the predominant pathway for Bax-induced cytochrome c release from MCF7
      mitochondria and for apoptosis induction in the whole cell. 

PMID- 23536164
TI  - Long-term reflux-related symptoms after bariatric surgery: comparison of sleeve
      gastrectomy versus laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Long-term pulmonary reflux-related symptoms following laparoscopic
      adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) have
      not been reported. METHODS: We designed a retrospective analysis of consecutive
      patients who underwent LAGB or LSG between January 2000 and December 2010. All
      patients provided detailed history and physical examination. We assessed both
      early and late reflux-related symptoms. All patients underwent spirometry and
      chest X-ray (CXR). RESULTS: The analysis included 307 patients who underwent
      either LAGB (n = 193) or LSG (n = 114). Mean age was 43 +/- 12 and 46 +/- 11
      years, respectively; 144 (76.6 %) and 83 (73 %) were female, respectively.
      Similar rates of previous pulmonary disease were noted in both LAGB and LSG
      groups (10.9 vs. 10.5 %, respectively). However, more patients with sleep apnea
      were in the LSG group (13.2 vs. 6.2 %, p = 0.03). The mean interval between
      surgery and the onset of pulmonary symptoms was longer in patients who underwent
      LAGB (72 +/- 22 months) than for those who had LSG (36 +/- 24 months; p = 0.03).
      The overall complication rate was higher in the LAGB (7.3 %) than in LSG (4.4 %)
      group. LSG patients had significantly lower rates of morning cough (12.3 vs. 59.6
      %, p = 0.001) and postprandial cough (10.5 vs. 58 %, p = 0.001) compared to the
      LAGB patients. Two cases of pneumonia occurred in each group. The mortality rate
      was zero in both groups. CONCLUSION: Both surgeries are considered safe and
      without major reflux-related symptoms. There is a lower incidence of cough with
      LSG than with LAGB.

PMID- 23536165
TI  - MELAS syndrome diagnosed in ICU in a 56-year-old patient presenting with status
      epilepticus.

PMID- 23536166
TI  - Cardiac support with IABP during venovenous ECMO for ARDS.

PMID- 23536168
TI  - Blindness: perceptions under mechanical ventilation.

PMID- 23536167
TI  - Increased morbidity and mortality in very preterm/VLBW infants with congenital
      heart disease.
AB  - PURPOSE: To study the association between congenital heart diseases (CHD) and in
      hospital mortality and morbidity of very preterm/very low birth weight (VLBW)
      infants. METHODS: The area-based prospective cohort study ACTION included all
      infants with gestational age (GA) 22-31 weeks or birth weight <1,500 g admitted
      to neonatal care between July 2003 and June 2005 in six Italian regions (n =
      3,684). CHD were coded according to ICD9-CM. Cluster multivariable logistic
      regression analyses were used to assess the relationship between CHD and
      mortality and selected morbidities [neonatal infection, ultrasound brain
      abnormalities, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia
      (BPD)] adjusting for potential confounders. RESULTS: Seventy-one patients had CHD
      [19.3 0/00, 95 % confidence interval (CI) 15.1-24.2 0/00]. The most common
      lesions were isolated atrial and ventricular septal defects (31.1 and 26.8 %,
      respectively), pulmonary valvar stenosis (12.7 %), and tetralogy of Fallot (5.6
      %). Compared with other infants, CHD patients showed significantly higher GA and
      frequency of small for gestational age (SGA, i.e., birth weight <=3rd centile).
      After adjustment for GA, sex, SGA, presence of extracardiac malformations or
      chromosomal anomalies, and region of birth, CHD patients had a significantly
      higher likelihood of infection, BPD, ROP, and, after 27 weeks gestation only,
      hospital mortality. The increased risk of ROP appeared to be partly due to
      infection. CONCLUSIONS: In very preterm/VLBW infants CHD are more prevalent than
      in the general liveborn population, and confer an increased risk of death and
      serious morbidities independently of other risk factors. These results may be
      useful to better tailor prognostic assessment and diagnostic and therapeutic
      interventions for these children.

PMID- 23536169
TI  - Severe adenoviral respiratory infection in children.

PMID- 23536170
TI  - Carbapenem-resistant Klebsiella pneumoniae in the CSF: smile, please! We are
      taking photos.

PMID- 23536171
TI  - Microwave-assisted solvothermal synthesis of zirconium oxide based metal-organic
      frameworks.
AB  - Zirconium oxide based Metal-Organic Frameworks were synthesised using a rapid and
      efficient microwave-assisted solvothermal method that produced purer phases and
      higher quality crystalline products in significantly (>95%) less time than the
      conventional heating method. A new amino-functionalised analogue has been
      synthesised exclusively using this microwave-assisted methodology.

PMID- 23536172
TI  - Chiral and achiral (imino)phenoxy-based cationic group 4 non-metallocene
      complexes as catalysts for polymerization of renewable alpha-methylene-gamma
      butyrolactones.
AB  - Protonolysis of M(Bn)4 (M = Zr, Ti; Bn = benzyl) with equimolar 2,4-di-tert-butyl
      6-[(2,6-diisopropylphenylimino)methyl]phenol [(2,6-(i)Pr2C6H3)N=C(3,5
      (t)Bu2C6H2)OH] in toluene at -30  degrees C to 25  degrees C cleanly affords the
      corresponding achiral (imino)phenoxy-tribenzyl complexes, [(2,6
      (i)Pr2C6H3)N=C(3,5-(t)Bu2C6H2)O]Zr(Bn)3 (1) and [(2,6-(i)Pr2C6H3)N=C(3,5
      (t)Bu2C6H2)O]Ti(Bn)3 (2). A chiral dibenzyl complex 3 incorporating the
      unsymmetric, tetradentate amino(imino)bis(phenoxy) ligand, [2,4-Br2C6H2(O)(6
      CH2(NC5H9))CH2N=CH(2-adamantyl-4-MeC6H2O)]Zr(Bn)2 (3), has also been prepared
      using the same protonolysis protocol. Abstractive activation of 1 with
      B(C6F5)3.THF in CD2Cl2 at room temperature (RT) affords clean, quantitative
      formation of the corresponding zirconium cation [((2,6-(i)Pr2C6H3)N=C(3,5
      (t)Bu2C6H2)O)Zr(Bn)2(THF)](+)[BnB(C6F5)3](-) (4). Likewise, benzyl abstraction of
      2 with B(C6F5)3.THF in CD2Cl2 at RT generates the cationic titanium complex
      [((2,6-(i)Pr2C6H3)N=C(3,5-(t)Bu2C6H2)O)Ti(Bn)2(THF)](+)[BnB(C6F5)3](-) (5),
      accompanied by a small amount of decomposed species as a result of C6F5 transfer.
      The dibenzyl cations 4 and 5 have been characterized spectroscopically, and their
      structures have been confirmed by single crystal X-ray diffraction analysis.
      Characteristics of the coordination polymerization of renewable alpha-methylene
      gamma-butyrolactone monomers by the cationic catalysts derived from achiral
      complexes 1 and 2 as well as chiral complex 3 have been investigated,
      representing the first study of such polymerization by non-metallocene catalysts.

PMID- 23536173
TI  - High activity catechol 1,2-dioxygenase from Stenotrophomonas maltophilia strain
      KB2 as a useful tool in cis,cis-muconic acid production.
AB  - This is the first report of a catechol 1,2-dioxygenase from Stenotrophomonas
      maltophilia strain KB2 with high activity against catechol and its methyl
      derivatives. This enzyme was maximally active at pH 8.0 and 40  degrees C and the
      half-life of the enzyme at this temperature was 3 h. Kinetic studies showed that
      the value of K m and V max was 12.8 MUM and 1,218.8 U/mg of protein,
      respectively. During our studies on kinetic properties of the catechol 1,2
      dioxygenase we observed substrate inhibition at >80 MUM. The nucleotide sequence
      of the gene encoding the S. maltophilia strain KB2 catechol 1,2-dioxygenase has
      high identity with other catA genes from members of the genus Pseudomonas. The
      deduced 314-residue sequence of the enzyme corresponds to a protein of molecular
      mass 34.5 kDa. This enzyme was inhibited by competitive inhibitors (phenol
      derivatives) only by ca. 30 %. High tolerance against condition changes is
      desirable in industrial processes. Our data suggest that this enzyme could be of
      use as a tool in production of cis,cis-muconic acid and its derivatives.

PMID- 23536174
TI  - 1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism
      in streptozotocin-induced diabetic mice.
AB  - We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and
      metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance
      tests and labeled (13)C6-glucose uptake assays suggested that DNJ inhibited
      intestinal glucose absorption in intestine. We also showed that DNJ down
      regulated intestinal SGLT1, Na(+)/K(+)-ATP and GLUT2 mRNA and protein expression.
      Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels
      of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of
      gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in
      hepatic cells and in vitro tests with purified enzymes indicated that the
      increased activity of glucose glycolysis enzymes was resulted from the relative
      increase in protein expression, rather than from direct enzyme activation. These
      results suggest that DNJ inhibits intestinal glucose absorption and accelerates
      hepatic glucose metabolism by directly regulating the expression of proteins
      involved in glucose transport systems, glycolysis and gluconeogenesis enzymes.

PMID- 23536175
TI  - Cylindrical axis, not epicondyles, approximates perpendicular to knee axes.
AB  - BACKGROUND: The transepicondylar axis (TEA) is often used as a surrogate for the
      flexion-extension axis, ie, the axis around which the tibia moves in space,
      because of a belief that both axes lie perpendicular to the mechanical axis.
      However, studies suggest the cylindrical axis (CA), defined as a line equidistant
      from contact points on the medial and lateral condylar surfaces from 10(o) to
      120(o) flexion, more closely approximates the axis around which the tibia moves
      in space. QUESTIONS/PURPOSES: We examined the TEA and CA angles relative to
      mechanical axes to determine whether one more consistently and closely
      approximates the surgical goal of orthogonality to the mechanical axis. METHODS:
      Three-dimensional (3-D) models were reconstructed from CT scans of five cadaver
      limbs. Three observers repeated three measurement sets to locate the TEA, CA, and
      femoral mechanical and tibial mechanical axes. Angles of the TEA and CA relative
      to the mechanical axes were calculated in two-dimensions (2-D) and as 3-D
      projections and compared for differences in magnitude and variance. RESULTS:
      Angles between CA and the mechanical axes were closer to 90 degrees  than the TEA
      in 2-D (92 degrees  versus 94 degrees  for the femur, 93 degrees  versus 94
      degrees  for the tibia) and 3-D (88 degrees  versus 87 degrees  for the femur, 88
      degrees  versus 86 degrees  for the tibia). Variance of the TEA was higher than
      the CA in 2-D. CONCLUSIONS: The CA forms angles more orthogonal to the mechanical
      axes of the thigh and leg than the TEA. CLINICAL RELEVANCE: Although we found a
      consistently greater deviation of the TEA from the mechanical axis than the CA
      with small differences, future studies will need to determine whether these
      differences are biomechanically or clinically important.

PMID- 23536176
TI  - The natural history of inflammatory pseudotumors in asymptomatic patients after
      metal-on-metal hip arthroplasty.
AB  - BACKGROUND: Although pseudotumors have been reported in 32% of asymptomatic metal
      on-metal hips, the natural history of asymptomatic pseudotumors is unknown.
      QUESTIONS/PURPOSES: The purpose of this study was to assess changes over time in
      asymptomatic pseudotumors and the effect of revision on pseudotumor mass.
      METHODS: Followup ultrasound was performed a mean of 25.8 months (range, 21-31
      months) after the detection of 15 pseudotumors and five isolated fluid
      collections in a cohort of 20 asymptomatic patients (13 metal-on-metal, three
      metal-on-polyethylene, and four hip resurfacings) [42]. Changes in pseudotumors
      and fluid collections size and nature, and serum ion levels were determined.
      RESULTS: Among the 15 nonrevised patients, pseudotumors increased in size in six
      (four solid and two cystic) of 10 patients, three of which had clinically
      important increases (13-148 cm(3); 28-74 cm(3); 47-104 cm(3)). Three pseudotumors
      (one solid and two cystic) disappeared completely (the largest measured 31
      cm(3)). One solid pseudotumor decreased in size (24 to 18 cm(3)). In five revised
      patients, pseudotumors completely disappeared in four patients. The fifth patient
      had two masses that decreased from 437 cm(3) to 262 cm(3) and 43 cm(3) to 25
      cm(3). All revision patients had a reduction of chromium (40.42 MU/L to 2.69
      MU/L) and cobalt ions (54.19 MU/L to 0.64 MU/L). Of five isolated fluid
      collections, four completely disappeared (two metal-on-metal and two metal-on
      polyethylene) and one (metal-on-metal) increased from 26 cm(3) to 136 cm(3).
      CONCLUSIONS: Our observations suggest pseudotumors frequently increase in size in
      asymptomatic patients with occasional remission of small masses. Revision
      resulted in remission of pseudotumors.

PMID- 23536177
TI  - Plain radiographs underestimate the asymmetry of the posterior condylar offset of
      the knee compared with MRI.
AB  - BACKGROUND: Restoration of posterior condylar offset (PCO) during total knee
      arthroplasty is essential to maximize range of motion, prevent impingement, and
      minimize flexion instability. Previously, PCO was determined with lateral
      radiographs, which could not distinguish the asymmetries between the femoral
      condyles. MRI can independently measure both medial and lateral PCO.
      QUESTIONS/PURPOSES: The purpose of this study is to determine the normal PCO of
      the knee, to establish the differences in medial and lateral PCO, and to compare
      PCO measurements obtained from radiographs versus those obtained from MRI.
      METHODS: We identified 32 patients without a history of prior knee pathology who
      had both plain radiographs and MRI scans of the same knee performed. The PCO was
      measured on lateral radiographs and compared with MRI measurements using a novel
      three-dimensional protocol. RESULTS: By MRI, the mean medial PCO was 29 (+/- 3)
      mm and the mean lateral PCO was 26 (+/- 3) mm; both values were greater (p <
      0.001 and p = 0.03, respectively) than the mean radiographic PCO of 25 (+/- 2)
      mm. The medial PCO, as measured by MRI, was significantly greater than the
      lateral PCO (p < 0.001). CONCLUSIONS: Plain radiographs underestimate PCO as well
      as the asymmetry of the medial and lateral PCO compared with MRI. This
      discrepancy is the result of both articular cartilage thickness and the anatomic
      differences between medial and lateral condyles. Designers of knee prostheses and
      instrumentation should take these differences into account.

PMID- 23536179
TI  - Update on stress fractures in female athletes: epidemiology, treatment, and
      prevention.
AB  - Stress fractures are a common type of overuse injury in athletes. Females have
      unique risk factors such as the female athlete triad that contribute to stress
      fracture injuries. We review the current literature on risk factors for stress
      fractures, including the role of sports participation and nutrition factors.
      Discussion of the management of stress fractures is focused on radiographic
      criteria and anatomic location and how these contribute to return to play
      guidelines. We outline the current recommendations for evaluating and treatment
      of female athlete triad. Technologies that may aid in recovery from a stress
      fracture including use of anti-gravity treadmills are discussed. Prevention
      strategies may include early screening of female athlete triad, promoting early
      participation in activities that improve bone health, nutritional strategies,
      gait modification, and orthotics.

PMID- 23536180
TI  - Molecular architecture of a sodium channel S6 helix: radial tuning of the voltage
      gated sodium channel 1.7 activation gate.
AB  - BACKGROUND: In-frame deletion mutation (Del-L955) in NaV1.7 sodium channel from a
      kindred with erythromelalgia hyperpolarizes activation. RESULTS: Del-L955 twists
      the S6 helix, displacing the Phe960 activation gate. Replacement of Phe960 at the
      correct helical position depolarizes activation. CONCLUSION: Radial tuning of the
      activation gate is critical to the activation of NaV1.7 channel. SIGNIFICANCE:
      Structural modeling guided electrophysiology reveals the functional importance of
      radial tuning of the S6 segment. Voltage-gated sodium (NaV) channels are membrane
      proteins that consist of 24 transmembrane segments organized into four homologous
      domains and are essential for action potential generation and propagation.
      Although the S6 helices of NaV channels line the ion-conducting pore and
      participate in channel activation, their functional architecture is incompletely
      understood. Our recent studies show that a naturally occurring in-frame deletion
      mutation (Del-L955) of NaV1.7 channel, identified in individuals with a severe
      inherited pain syndrome (inherited erythromelalgia) causes a substantial
      hyperpolarizing shift of channel activation. Here we took advantage of this
      deletion mutation to understand the role of the S6 helix in the channel
      activation. Based on the recently published structure of a bacterial NaV channel
      (NaVAb), we modeled the WT and Del-L955 channel. Our structural model showed that
      Del-L955 twists the DII/S6 helix, shifting location and radial orientation of the
      activation gate residue (Phe(960)). Hypothesizing that these structural changes
      produce the shift of channel activation of Del-L955 channels, we restored a
      phenylalanine in wild-type orientation by mutating Ser(961) (Del-L955/S961F),
      correcting activation by ~10 mV. Correction of the displaced Phe(960) (F960S)
      together with introduction of the rescuing activation gate residue (S961F)
      produced an additional ~6-mV restoration of activation of the mutant channel. A
      simple point mutation in the absence of a twist (L955A) did not produce a radial
      shift and did not hyperpolarize activation. Our results demonstrate the
      functional importance of radial tuning of the sodium channel S6 helix for the
      channel activation.

PMID- 23536181
TI  - Specificity of Processing alpha-glucosidase I is guided by the substrate
      conformation: crystallographic and in silico studies.
AB  - BACKGROUND: The enzyme "GluI" is key to the synthesis of critical glycoproteins
      in the cell. RESULTS: We have determined the structure of GluI, and modeled
      binding with its unique sugar substrate. CONCLUSION: The specificity of this
      interaction derives from a unique conformation of the substrate. SIGNIFICANCE:
      Understanding the mechanism of the enzyme is of basic importance and relevant to
      potential development of antiviral inhibitors. Processing alpha-glucosidase I
      (GluI) is a key member of the eukaryotic N-glycosylation processing pathway,
      selectively catalyzing the first glycoprotein trimming step in the endoplasmic
      reticulum. Inhibition of GluI activity impacts the infectivity of enveloped
      viruses; however, despite interest in this protein from a structural, enzymatic,
      and therapeutic standpoint, little is known about its structure and enzymatic
      mechanism in catalysis of the unique glycan substrate Glc3Man9GlcNAc2. The first
      structural model of eukaryotic GluI is here presented at 2-A resolution. Two
      catalytic residues are proposed, mutations of which result in catalytically
      inactive, properly folded protein. Using Autodocking methods with the known
      substrate and inhibitors as ligands, including a novel inhibitor characterized in
      this work, the active site of GluI was mapped. From these results, a model of
      substrate binding has been formulated, which is most likely conserved in
      mammalian GluI.

PMID- 23536182
TI  - Perturbation of transcription factor Nur77 expression mediated by myocyte
      enhancer factor 2D (MEF2D) regulates dopaminergic neuron loss in response to 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
AB  - We have earlier reported the critical nature of calpain-CDK5-MEF2 signaling in
      governing dopaminergic neuronal loss in vivo. CDK5 mediates phosphorylation of
      the neuronal survival factor myocyte enhancer factor 2 (MEF2) leading to its
      inactivation and loss. However, the downstream factors that mediate MEF2
      regulated survival are unknown. Presently, we define Nur77 as one such critical
      downstream survival effector. Following 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) treatment in vivo, Nur77 expression in the
      nigrostriatal region is dramatically reduced. This loss is attenuated by
      expression of MEF2. Importantly, MEF2 constitutively binds to the Nur77 promoter
      in neurons under basal conditions. This binding is lost following 1-methyl-4
      phenylpyridinium treatment. Nur77 deficiency results in significant sensitization
      to dopaminergic loss following 1-methyl-4-phenylpyridinium/MPTP treatment, in
      vitro and in vivo. Furthermore, Nur77-deficient MPTP-treated mice displayed
      significantly reduced levels of dopamine and 3,4-Dihydroxyphenylacetic acid in
      the striatum as well as elevated post synaptic FosB activity, indicative of
      increased nigrostriatal damage when compared with WT MPTP-treated controls.
      Importantly, this sensitization in Nur77-deficient mice was rescued with ectopic
      Nur77 expression in the nigrostriatal system. These results indicate that the
      inactivation of Nur77, induced by loss of MEF2 activity, plays a critical role in
      nigrostriatal degeneration in vivo.

PMID- 23536183
TI  - Alternative C-terminal helix orientation alters chemokine function: structure of
      the anti-angiogenic chemokine, CXCL4L1.
AB  - BACKGROUND: CXCL4L1 is a highly potent anti-angiogenic and anti-tumor chemokine,
      and its structural information is unknown. RESULTS: CXCL4L1 x-ray structure is
      determined, and it reveals a previously unrecognized chemokine structure adopting
      a novel C-terminal helix conformation. CONCLUSION: The alternative helix
      conformation enhances the anti-angiogenic activity of CXCL4L1 by reducing the
      glycosaminoglycan binding ability. SIGNIFICANCE: Chemokine C-terminal helix
      orientation is critical in regulating their functions. Chemokines, a subfamily of
      cytokines, are small, secreted proteins that mediate a variety of biological
      processes. Various chemokines adopt remarkable conserved tertiary structure
      comprising an anti-parallel beta-sheet core domain followed by a C-terminal helix
      that packs onto the beta-sheet. The conserved structural feature has been
      considered critical for chemokine function, including binding to cell surface
      receptor. The recently isolated variant, CXCL4L1, is a homologue of CXCL4
      chemokine (or platelet factor 4) with potent anti-angiogenic activity and
      differed only in three amino acid residues of P58L, K66E, and L67H. In this study
      we show by x-ray structural determination that CXCL4L1 adopts a previously
      unrecognized structure at its C terminus. The orientation of the C-terminal helix
      protrudes into the aqueous space to expose the entire helix. The alternative
      helix orientation modifies the overall chemokine shape and surface properties.
      The L67H mutation is mainly responsible for the swing-out effect of the helix,
      whereas mutations of P58L and K66E only act secondarily. This is the first
      observation that reports an open conformation of the C-terminal helix in a
      chemokine. This change leads to a decrease of its glycosaminoglycan binding
      properties and to an enhancement of its anti-angiogenic and anti-tumor effects.
      This unique structure is recent in evolution and has allowed CXCL4L1 to gain
      novel functional properties.

PMID- 23536184
TI  - The Arf/p53 protein module, which induces apoptosis, down-regulates histone H2AX
      to allow normal cells to survive in the presence of anti-cancer drugs.
AB  - BACKGROUND: It is unclear how DNA-damaging agents target cancer cells over normal
      somatic cells. RESULTS: Arf/p53-dependent down-regulation of H2AX enables normal
      cells to survive after DNA damage. CONCLUSION: Transformed cells, which harbor
      mutations in either Arf or p53, are more sensitive to DNA-damaging agents.
      SIGNIFICANCE: Cellular transformation renders cells more susceptible to some DNA
      damaging agents. Anti-cancer drugs generally target cancer cells rather than
      normal somatic cells. However, the factors that determine this differential
      sensitivity are poorly understood. Here we show that Arf/p53-dependent down
      regulation of H2AX induced the selective survival of normal cells after drug
      treatment, resulting in the preferential targeting of cancer cells. Treatment
      with camptothecin, a topoisomerase I inhibitor, caused normal cells to down
      regulate H2AX and become quiescent, a process mediated by both Arf and p53. In
      contrast, transformed cells that harbor mutations in either Arf or p53 do not
      down-regulate H2AX and are more sensitive to drugs unless they have developed
      drug resistance. Such transformation-associated changes in H2AX expression
      rendered cancer cells more susceptible to drug-induced damage (by two orders of
      magnitude). Thus, the expression of H2AX and gammaH2AX (phosphorylated form of
      H2AX at Ser-139) is a critical factor that determines drug sensitivity and should
      be considered when administering chemotherapy.

PMID- 23536186
TI  - Regulation of primary response genes in B cells.
AB  - Deregulated gene expression in B cells often results in various lymphoid
      malignancies and immune deficiencies. Therefore, understanding signal-induced
      gene regulatory pathways involved during B cell activation is important to tackle
      pathologies associated with altered B cell function. Primary response genes
      (PRGs) are rapidly induced upon signaling in B cells and other cell types and
      often encode oncogenic transcription factors, which are associated with various
      malignancies. However, an important issue that remains unclear is whether the
      fundamental mechanism of activation of these genes is essentially the same under
      such diverse conditions. c-fos is a PRG that is induced rapidly upon activation
      of B cells in response to a wide variety of stimuli. Using the c-fos gene as a
      candidate PRG, we addressed here how it is regulated in response to tumor
      promoting and antigen-mimicking signals. Our results show that although the mRNA
      was induced and extinguished within minutes in response to both signals,
      surprisingly, apparently full-length unspliced pre-mRNA persisted for several
      hours in both cases. However, although the mitogenic signal resulted in a more
      sustained mRNA response that persisted for 4 h, antigenic signaling resulted in a
      more robust but very transient response that lasted for <1 h. Moreover, the pre
      mRNA profile exhibited significant differences between the two signals.
      Additionally, the splicing regulation was also observed with egr-2, but not with
      c-myc. Together, these results suggest a previously underappreciated regulatory
      step in PRG expression in B cells.

PMID- 23536187
TI  - The auxiliary subunit KChIP2 is an essential regulator of homeostatic
      excitability.
AB  - BACKGROUND: The necessity for, or redundancy of, distinctive KChIP proteins is
      not known. RESULTS: Deletion of KChIP2 leads to increased susceptibility to
      epilepsy and to a reduction in IA and increased excitability in pyramidal
      hippocampal neurons. CONCLUSION: KChIP2 is essential for homeostasis in
      hippocampal neurons. SIGNIFICANCE: Mutations in K(A) channel auxiliary subunits
      may be loci for epilepsy. The somatodendritic IA (A-type) K(+) current underlies
      neuronal excitability, and loss of IA has been associated with the development of
      epilepsy. Whether any one of the four auxiliary potassium channel interacting
      proteins (KChIPs), KChIP1-KChIP4, in specific neuronal populations is critical
      for IA is not known. Here we show that KChIP2, which is abundantly expressed in
      hippocampal pyramidal cells, is essential for IA regulation in hippocampal
      neurons and that deletion of Kchip2 affects susceptibility to limbic seizures.
      The specific effects of Kchip2 deletion on IA recorded from isolated hippocampal
      pyramidal neurons were a reduction in amplitude and shift in the V1/2 for steady
      state inactivation to hyperpolarized potentials when compared with WT neurons.
      Consistent with the relative loss of IA, hippocampal neurons from Kchip2(-/-)
      mice showed increased excitability. WT cultured neurons fired only occasional
      single action potentials, but the average spontaneous firing rate (spikes/s) was
      almost 10-fold greater in Kchip2(-/-) neurons. In slice preparations, spontaneous
      firing was detected in CA1 pyramidal neurons from Kchip2(-/-) mice but not from
      WT. Additionally, when seizures were induced by kindling, the number of
      stimulations required to evoke an initial class 4 or 5 seizure was decreased, and
      the average duration of electrographic seizures was longer in Kchip2(-/-) mice
      compared with WT controls. Together, these data demonstrate that the KChIP2 is
      essential for physiologic IA modulation and homeostatic stability and that there
      is a lack of functional redundancy among the different KChIPs in hippocampal
      neurons.

PMID- 23536185
TI  - Protein phosphatase 2A and DNA-dependent protein kinase are involved in mediating
      rapamycin-induced Akt phosphorylation.
AB  - BACKGROUND: The mechanisms underlying rapamycin-induced Akt phosphorylation have
      not been fully elucidated. RESULTS: Inhibition of PP2A or DNA-PK attenuates or
      abrogates rapamycin-induced Akt phosphorylation and co-inhibition of mTOR and DNA
      PK enhances anticancer activity. CONCLUSION: PP2A-dependent and DNA-PK-mediated
      mechanism is involved in rapamycin-induced Akt phosphorylation. SIGNIFICANCE: A
      previously unknown mechanism underlying rapamycin-induced Akt phosphorylation and
      a novel strategy to enhance mTOR-targeted cancer therapy may be suggested.
      Inhibition of mammalian target of rapamycin complex 1 (mTORC1), for example with
      rapamycin, increases Akt phosphorylation while inhibiting mTORC1 signaling.
      However, the underlying mechanisms have not been fully elucidated. The current
      study has uncovered a previously unknown mechanism underlying rapamycin-induced
      Akt phosphorylation involving protein phosphatase 2A (PP2A)-dependent DNA protein
      kinase (DNA-PK) activation. In several cancer cell lines, inhibition of PP2A with
      okadaic acid, fostriecin, small T antigen, or PP2A knockdown abrogated rapamycin
      induced Akt phosphorylation, and rapamycin increased PP2A activity. Chemical
      inhibition of DNA-PK, knockdown or deficiency of DNA-PK catalytic subunit (DNA
      PKcs), or knock-out of the DNA-PK component Ku86 inhibited rapamycin-induced Akt
      phosphorylation. Exposure of cancer cells to rapamycin increased DNA-PK activity,
      and gene silencing-mediated PP2A inhibition attenuated rapamycin-induced DNA-PK
      activity. Collectively these results suggest that rapamycin induces PP2A
      dependent and DNA-PK-mediated Akt phosphorylation. Accordingly, simultaneous
      inhibition of mTOR and DNA-PK did not stimulate Akt activity and synergistically
      inhibited the growth of cancer cells both in vitro and in vivo. Thus, our
      findings also suggest a novel strategy to enhance mTOR-targeted cancer therapy by
      co-targeting DNA-PK.

PMID- 23536189
TI  - Interfacial microfluidic transport on micropatterned superhydrophobic textile.
AB  - Textile-enabled interfacial microfluidics, utilizing fibrous hydrophilic yarns
      (e.g., cotton) to guide biological reagent flows, has been extended to various
      biochemical analyses recently. The restricted capillary-driving mechanism,
      however, persists as a major challenge for continuous and facilitated biofluidic
      transport. In this paper, we have first introduced a novel interfacial
      microfluidic transport principle to drive three-dimensional liquid flows on a
      micropatterned superhydrophobic textile (MST) platform in a more autonomous and
      controllable manner. Specifically, the MST system utilizes the surface tension
      induced Laplace pressure to facilitate the liquid motion along the hydrophilic
      yarn, in addition to the capillarity present in the fibrous structure. The
      fabrication of MST is simply accomplished by stitching hydrophilic cotton yarn
      into a superhydrophobic fabric substrate (contact angle 140 +/- 3 degrees ), from
      which well-controlled wetting patterns are established for interfacial
      microfluidic operations. The geometric configurations of the stitched
      micropatterns, e.g., the lengths and diameters of the yarn and bundled
      arrangement, can all influence the transport process, which is investigated both
      experimentally and theoretically. Two operation modes, discrete and continuous
      transport, are also presented in detail. In addition, the gravitational effect as
      well as the droplet removal process have been also considered and quantitatively
      analysed during the transport process. As a demonstration, an MST design has been
      implemented on an artificial skin surface to collect and remove sweat in a highly
      efficient and facilitated means. The results have illustrated that the novel
      interfacial transport on the textile platform can be potentially extended to a
      variety of biofluidic collection and removal applications.

PMID- 23536188
TI  - NemR is a bleach-sensing transcription factor.
AB  - BACKGROUND: Little is known about how bacteria sense or respond to reactive
      chlorine species, such as bleach. RESULTS: NemR is a redox-regulated
      transcription factor which senses bleach. CONCLUSION: NemR controls expression of
      genes encoding electrophile detoxification enzymes, which increase bleach
      resistance. SIGNIFICANCE: We demonstrate a bleach-sensing bacterial response
      system and a new mechanism contributing to bacterial bleach survival.
      Hypochlorous acid (HOCl), the active component of household bleach, also
      functions as a powerful antimicrobial during the innate immune response. Despite
      its widespread use, surprisingly little is known about how cells sense or respond
      to HOCl. We now demonstrate that Escherichia coli NemR is a redox-regulated
      transcriptional repressor, which uses the oxidation status of HOCl-sensitive
      cysteine residues to respond to bleach and related reactive chlorine species.
      NemR controls bleach-mediated expression of two enzymes required for
      detoxification of reactive electrophiles: glyoxalase I and N-ethylmaleimide
      reductase. Both enzymes contribute to bacterial bleach survival. These results
      provide evidence that bleach resistance relies on the capacity of organisms to
      specifically sense reactive chlorine species and respond with the up-regulation
      of enzymes dedicated to detoxification of methylglyoxal and other reactive
      electrophiles.

PMID- 23536190
TI  - Supramolecular control of cell adhesion via ferrocene-cucurbit[7]uril host-guest
      binding on gold surfaces.
AB  - Supramolecular control of adhesion of cells is demonstrated using synthetic
      integrin binding RGD peptide-ferrocene conjugates that were immobilized via host
      guest chemistry onto cucurbit[7]uril coated gold surfaces.

PMID- 23536191
TI  - Lower vitamin E serum levels are associated with osteoporosis in early
      postmenopausal women: a cross-sectional study.
AB  - The aim of this study was to evaluate the relationship between vitamin E status
      and osteoporosis in early postmenopausal women. Anthropometric data, osteoporosis
      risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum
      parameters which may influence bone mineral density in postmenopausal women were
      analyzed in a cross-sectional study. The association between osteoporosis and
      age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin
      E (measured as 25 hydroxyvitamin D and as alpha-tocopherol:lipids ratio,
      respectively), bone alkaline phosphatase, smoking status, leisure physical
      activity and alcohol intake were modeled by a multivariate logistic regression
      and multi-linear regression analysis in 232 early postmenopausal women. A lower
      vitamin E:lipid ratio was associated with osteoporosis in multivariate logistic
      regression. In a multivariate linear model with BMD of the lumbar spine as a
      dependent variable, the vitamin E:lipid ratio was clearly related with BMD of the
      lumbar spine (F ratio = 6.30, p = 0.002). BMD of the lumbar spine was
      significantly higher in the highest tertile of the vitamin E:lipid ratio than in
      the lowest tertile. The mean vitamin E:lipid ratio was significantly lower in
      osteoporotic postmenopausal women (T score <=-2.5) (3.0 +/- 0.6 MUmol/mmol) than
      normal (neither osteoporotic nor osteopenic) postmenopausal women (T score >-1)
      (3.5 +/- 0.7 MUmol/mmol) using multivariable-adjusted BMD. These findings
      highlight that vitamin E may increase BMD in healthy postmenopausal women. 

PMID- 23536192
TI  - Osteoporosis and treatments in Japan: management for preventing subsequent
      fractures.
AB  - Prevalent fractures are major contributors to an increased risk of subsequent
      fractures, particularly in people with osteoporosis. While many studies have been
      conducted to assess the incidence of fracture in Japanese people with
      osteoporosis, far fewer have been conducted to assess the risk of subsequent
      fractures. This article reviews the morbidity, mortality, and risk of fracture in
      patients who are at high risk of subsequent fracture in Japan and the current
      treatment options available for these patients. Osteoporotic fractures in Japan
      are associated with high morbidity and mortality that result in significant
      financial and social costs. The rise in the proportion of elderly women in the
      Japanese population is contributing to a greater proportion of people with
      osteoporotic fractures and the high cost of osteoporosis. Although hip fractures
      have a significant effect on costs, a greater proportion of the Japanese
      population experience vertebral fractures. An increase in the incidence of
      vertebral fractures is concerning because preexisting vertebral fractures in
      older patients are associated with an increased risk of subsequent fractures.
      Hence, there is a clear rationale for pharmacological treatment of patients with
      prevalent vertebral fractures, or for those who are hospitalized or undergo
      surgery for osteoporotic fractures. Several pharmacological therapies are now
      available in Japan for the treatment of patients with osteoporosis. Understanding
      the consequences of subsequent fractures and the treatment options available for
      patients at high risk of subsequent fractures may contribute to clinical decision
      making and improved outcomes for patients with osteoporosis. 

PMID- 23536193
TI  - Suppression of osteoclastogenesis through phosphorylation of eukaryotic
      translation initiation factor 2 alpha.
AB  - In response to various stresses including viral infection, nutrient deprivation,
      and stress to the endoplasmic reticulum, eukaryotic translation initiation factor
      2 alpha (eIF2alpha) is phosphorylated to cope with stress induced apoptosis.
      Although bone cells are sensitive to environmental stresses that alter the
      phosphorylation level of eIF2alpha, little is known about the role of eIF2alpha
      mediated signaling during the development of bone-resorbing osteoclasts. Using
      two chemical agents (salubrinal and guanabenz) that selectively inhibit de
      phosphorylation of eIF2alpha, we evaluated the effects of phosphorylation of
      eIF2alpha on osteoclastogenesis of RAW264.7 pre-osteoclasts as well as
      development of MC3T3 E1 osteoblast-like cells. The result showed that salubrinal
      and guanabenz stimulated matrix deposition of osteoblasts through upregulation of
      activating transcription factor 4 (ATF4). The result also revealed that these
      agents reduced expression of the nuclear factor of activated T cells c1 (NFATc1)
      and inhibited differentiation of RAW264.7 cells to multi-nucleated osteoclasts.
      Partial silencing of eIF2alpha with RNA interference reduced suppression of
      salubrinal/guanabenz-driven downregulation of NFATc1. Collectively, we
      demonstrated that the elevated phosphorylation level of eIF2alpha not only
      stimulates osteoblastogenesis but also inhibit osteoclastogenesis through
      regulation of ATF4 and NFATc1. The results suggest that eIF2alpha-mediated
      signaling might provide a novel therapeutic target for preventing bone loss in
      osteoporosis. 

PMID- 23536194
TI  - Health literacy, health communication challenges, and cancer screening among
      rural native Hawaiian and Filipino women.
AB  - Native Hawaiians and Filipinos are disproportionately impacted by cancer and are
      less likely to participate in cancer screening than whites. Limited information
      exists about health information pathways and health communication challenges as
      they relate to cancer screening in these groups. Six focus groups (n=77) of
      Native Hawaiian and Filipino women age 40+years were conducted to investigate
      these research gaps. Participants noted many health information challenges.
      Challenges were both practical and interpersonal and included both written and
      oral health communication. Practical challenges included "big" words, complexity
      of terms, and lack of plain English. Interpersonal issues included doctors
      rushing, doctors not assessing comprehension, and doctors treating respondents as
      patients not people. Women noted that they would often not ask questions even
      when they knew they did not understand because they did not want the provider to
      think negatively of them. Overarching themes to improve cancer communication gaps
      included: (1) the importance of family and community in health information
      dissemination, (2) the key role women play in interpreting health information for
      others, (3) the importance of personal experience and relationships to the
      salience of health information, and (4) the desire for local cultural relevance
      in health communication. Findings are discussed in light of the 2010 National
      Action Plan for Health Literacy.

PMID- 23536195
TI  - Surgical resection of recurrent colonic cancer.
AB  - BACKGROUND: Locoregional recurrence of colonic cancer includes anastomotic
      recurrence, associated nodal masses, masses that involve the abdominal wall and
      pelvic masses. The aim of this study was to report the outcome of resection of
      such recurrences and to provide guidance on the management of this disease.
      METHODS: Patients were identified from a prospectively maintained database. Data
      were obtained on demographics, surgical procedure, morbidity, histopathology and
      outcome. Univariable and multivariable analyses of factors influencing survival
      were performed using stepwise Cox logistic regression. RESULTS: Forty-two
      patients (21 men; median age 61 (range 41-82) years) underwent resection of
      recurrent colonic cancer between 2003 and 2011. The median interval between
      resection of the primary and recurrent colonic tumour was 37.5 (interquartile
      range 7-91) months. The recurrences developed at the previous anastomosis (9
      patients), elsewhere within the abdominal cavity or wall (8) and as discrete
      masses within the pelvic cavity (25). Eighteen of 42 patients underwent resection
      of hepatic or pulmonary metastases at some stage after resection of the primary
      tumour. Median survival was 29 months after R0 resection and 26 months after R1
      resection of the recurrent tumour (P = 0.226). The survival benefit depended on
      the location of the recurrence (median survival after resection of recurrent
      disease: anastomotic 33 months, pelvic 26 months, abdominal 19 months; P =
      0.010). CONCLUSION: This study described a classification system, management
      algorithm and prognostic factors for recurrent colonic cancer. The distribution
      of disease influenced survival. Long-term survival was achieved, including a
      subset of patients with drop metastases and/or previous metastasectomy.

PMID- 23536196
TI  - Human T regulatory cells: on the way to cognition.
AB  - Forkhead box P3 (Foxp3)(+) T regulatory (Treg) cells are powerful controllers of
      the immune response and their role in the human immune system is indispensable.
      Since a number of revolutionary and very convincing results were brought to
      light, Foxp3 has unquestionably been thought to be the "master regulator" of Treg
      lineage commitment. Herein, we depict the revised view on the role of Foxp3
      transcription factor, challenging this theory, as well as the growing
      significance of Runt-related transcription factor (RUNX) family proteins for Treg
      lineage. The review presents the current notion of Treg cell heterogeneity,
      molecular characteristics and their mechanisms of action.

PMID- 23536197
TI  - Quantitative determination of valproic acid in postmortem blood samples--evidence
      of strong matrix dependency and instability.
AB  - Most of the daily work of forensic toxicologists deals with fatal cases resulting
      from overdoses of licit and illicit drugs. However, another reason for fatalities
      in patients suffering from epilepsy can be undetectable or subtherapeutic levels
      of antiepileptic drugs. Some studies have shown a correlation between "sudden
      unexpected death in epilepsy" (SUDEP) and the ineffective treatment of epilepsy.
      Low levels of antiepileptic drugs may be a risk factor for SUDEP. The death of a
      psychiatric patient also suffering from epilepsy inspired the investigation.
      Subsequent to the death of the patient, the doctor was accused of providing
      inadequate therapy for epilepsy. The patient was to be treated with valproic
      acid. We developed and validated a simple method of determining valproic acid
      levels by gas chromatography-mass spectrometry for serum, but a transfer of the
      method from serum to postmortem whole blood failed. The method had to be modified
      and revalidated for postmortem whole blood specimens. A stability study of
      valproic acid in postmortem blood was conducted, showing a decline of valproic
      acid levels by 85 % after storage at room temperature for 28 days. During the
      storage time, the blood samples showed changes in consistency. Depending on the
      stage of decomposition, it is necessary to perform a determination by standard
      addition with an equilibration time of 4 h before extraction to achieve reliable
      results. For a proper interpretation of quantitative results, it is necessary to
      keep the postmortem decline of valproic acid concentrations in mind. 

PMID- 23536198
TI  - Effects of single and combined cell treatments based on low pH and high
      concentrations of ethanol on the growth and fermentation of Dekkera bruxellensis
      and Saccharomyces cerevisiae.
AB  - The alcoholic fermentation in Brazil displays some peculiarities because the
      yeast used is recycled in a non-aseptic process. After centrifugation, the cells
      are treated with acid to control the bacterial growth. However, it is difficult
      to manage the indigenous yeasts without affecting the main culture of
      Saccharomyces cerevisiae. This work evaluated how the cell treatment could be
      modified to combat contaminant yeasts based on the differential sensitivities to
      low pH and high concentrations of ethanol displayed by an industrial strain of S.
      cerevisiae and three strains of Dekkera bruxellensis, which are common
      contaminant yeasts in Brazilian fermentation processes. The tests were initially
      performed in rich medium with a low pH or a high concentration of ethanol to
      analyse the yeast growth profile. Then, the single and combined effects of low pH
      and ethanol concentration on the yeast cell viability were evaluated under non
      proliferative conditions. The effects on the fermentation parameters were also
      verified. S. cerevisiae grew best when not subjected to the stresses, but this
      yeast and D. bruxellensis had similar growth kinetics when exposed to a low pH or
      increased ethanol concentrations. However, the combined treatments of low pH
      (2.0) and ethanol (11 or 13 %) resulted in a decrease of D. bruxellensis cell
      viability almost three times higher than of S. cerevisiae, which was only
      slightly affected by all cell treatments. The initial viability of the treated
      cells was restored within 8 h of growth in sugar cane juice, with the exception
      of the combined treatment for D. bruxellensis. The ethanol-based cell treatment,
      in despite of slowing the fermentation, could decrease and maintain D.
      bruxellensis population under control while S. cerevisiae was taking over the
      fermentation along six fermentative cycles. These results indicate that it may be
      possible to control the growth of D. bruxellensis without major effects on S.
      cerevisiae. The cells could be treated between the fermentation cycles by the
      parcelled addition of 13 % ethanol to the tanks in which the yeast cream is
      treated with sulphuric acid at pH 2.0. 

PMID- 23536200
TI  - Anti-caspase-3 preconditioning increases proinsulin secretion and deteriorates
      posttransplant function of isolated human islets.
AB  - Human islet isolation is associated with adverse conditions inducing apoptosis
      and necrosis. The aim of the present study was to assess whether antiapoptotic
      preconditioning can improve in vitro and posttransplant function of isolated
      human islets. A dose-finding study demonstrated that 200 MUmol/L of the caspase-3
      inhibitor Ac-DEVD-CMK was most efficient to reduce the expression of activated
      caspase-3 in isolated human islets exposed to severe heat shock. Ac-DEVD-CMK
      pretreated or sham-treated islets were transplanted into immunocompetent or
      immunodeficient diabetic mice and subjected to static glucose incubation to
      measure insulin and proinsulin secretion. Antiapoptotic pretreatment
      significantly deteriorated graft function resulting in elevated nonfasting serum
      glucose when compared to sham-treated islets transplanted into diabetic nude mice
      (p < 0.01) and into immunocompetent mice (p < 0.05). Ac-DEVD-CMK pretreatment did
      not significantly change basal and glucose-stimulated insulin release compared to
      sham-treated human islets but increased the proinsulin release at high glucose
      concentrations (20 mM) thus reducing the insulin-to-proinsulin ratio in
      preconditioned islets (p < 0.05). This study demonstrates that the caspase-3
      inhibitor Ac-DEVD-CMK interferes with proinsulin conversion in preconditioned
      islets reducing their potency to cure diabetic mice. The mechanism behind this
      phenomenon is unclear so far but may be related to the ketone CMK linked to the
      Ac-DEVD molecule. Further studies are required to identify biocompatible caspase
      inhibitors suitable for islet preconditioning.

PMID- 23536199
TI  - Enhanced antibacterial and anti-quorum sensing activities of triclosan by
      complexation with modified beta-cyclodextrins.
AB  - Triclosan (TCS), an antimicrobial agent widely used in consumer and medical
      products, was complexed with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and
      methyl-beta-cyclodextrin (MbetaCD). Phase-solubility studies indicated that
      inclusion complexes of 1:1 stoichiometry were formed and allowed estimation of
      the associated equilibrium constants and free-energy changes. At the highest
      cyclodextrin concentrations investigated, an almost 20-fold increase in the
      apparent water solubility of TCS was determined. Susceptibility tests against
      Escherichia coli and Staphylococcus aureus showed that the TCS-HPbetaCD and TCS
      MbetaCD complexes exhibited antibacterial properties higher than those of
      uncomplexed TCS. The two complexes were also found capable of interfering with
      cell-to-cell communication mechanisms in the C. violaceum model system relying on
      N-acylhomoserine lactone autoinducers. The inhibitory activity of TCS increased
      significantly upon inclusion of the drug in HPbetaCD or MbetaCD, with small
      differences between the two CDs. The results obtained suggest that the
      investigated complexes could be used for treating infections caused by TCS
      susceptible pathogens or for preventing biofilm formation on indwelling medical
      devices such as catheters, stents and orthopedic implants. 

PMID- 23536201
TI  - Design and synthesis of an on-off "click" fluorophore that executes a logic
      operation and detects heavy and transition metal ions in water and living cells.
AB  - We have designed and synthesized a novel fluorescent molecular probe using the
      Cu(i)-catalyzed Huisgen cycloaddition of 1,3-diethynyl-6-fluoroisoquinoline with
      1-(2-azidoethyl)pyrrolidine. This water soluble "click" fluorescent chemosensor
      displays good sensitivity towards heavy and transition metal ions. It shows
      pronounced fluorescence enhancement and high selectivity for Zn(2+) over other
      biologically relevant metal ions in water at pH 7.0. The fluorescence response of
      the bis-triazole derivative in the presence of Zn(2+) is switchable and
      reversible as a function of pH. The chemosensor also exhibits fluorescence
      quenching with Fe(2+) and Cu(2+) in water at pH 7.0. A modified YES logic gate
      property has been proposed using the "turn-on" and "turn-off" behavior of the bis
      triazole with Zn(2+) and Fe(2+). The sensor is cell membrane permeable and
      applicable for intracellular Zn(2+) imaging.

PMID- 23536203
TI  - Assessment and confirmation of tracheal intubation when capnography fails: a
      novel use for an USB camera.
AB  - A 62 year old male with a right pyriform fossa lesion extending to the right
      arytenoid and obscuring the glottic inlet was planned for laser assisted
      excision. Direct laryngoscopic assessment after topicalization of the airway,
      showed a Cormack Lehane grade 3 view. We report a case where, in the absence of a
      fiberscope, a novel inexpensive Universal Serial Bus camera was used to obtain an
      optimal laryngoscopic view. This provided direct visual confirmation of tracheal
      intubation with a Laser Flex tube, when capnography failed to show any trace.
      Capnography may not be reliable as a sole indicator of confirmation of correct
      endotracheal tube placement. Video laryngoscopy may provide additional
      confirmation of endotracheal intubation. 

PMID- 23536204
TI  - The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is an
      outcome predictor for partially matched related donor transplantation.
AB  - To validate the predictive ability of the Hematopoietic Cell Transplantation
      Specific Comorbidity Index (HCT-CI) on the outcome of hematopoietic stem cell
      transplantation (HSCT) patients who received transplants from partially matched
      related donors (PMRD), a total of 526 patients who received PMRD HSCT between
      January 2006 and December 2009 at the Institute of Hematology, Peking University
      were enrolled. Patients were grouped according to their HCT-CI score; 31.0%,
      31.4%, and 37.6% of patients had HCT-CI scores of 0, 1-2, and >=3, respectively.
      Patients with HCT-CI scores of >=3 had a significantly poorer 2-year overall
      survival (OS) than patients with HCT-CI scores of 0-2 (54.55% vs. 78.05%, P <
      0.001). In addition, patients with HCT-CI scores of >=3 had a significantly
      higher 2-year cumulative incidence of relapse and nonrelapse mortality (NRM) than
      patients with scores of 0-2 (relapse: 23.23% vs. 11.59%, P < 0.001; NRM: 34.30%
      vs. 15.93%, P < 0.001). HCT-CI scores of <3 were associated with better OS, less
      relapse, and lower NRM in multivariate analysis. Patients who had high
      comorbidity scores as well as high-risk disease had the poorest outcomes.
      Therefore, we found that HCT-CI is associated with the outcomes of PMRD HSCT and
      we should closely monitor patients with a high comorbidity burden.

PMID- 23536202
TI  - The UPR and lung disease.
AB  - The respiratory tract has a surface area of approximately 70 m(2) that is in
      direct contact with the external environment. Approximately 12,000 l of air are
      inhaled daily, exposing the airway epithelium to up to 25 million particles an
      hour. Several inhaled environmental triggers, like cigarette smoke, diesel
      exhaust, or allergens, are known inducers of endoplasmatic reticulum (ER) stress
      and cause a dysregulation in ER homeostasis. Furthermore, some epithelial cell
      types along the respiratory tract have a secretory function, producing large
      amounts of mucus or pulmonary surfactant, as well as innate host defense
      molecules like defensins. To keep up with their secretory demands, these cells
      must rely on the appropriate functioning and folding capacity of the ER, and they
      are particularly more vulnerable to conditions of unresolved ER stress. In the
      lung interstitium, triggering of ER stress pathways has a major impact on the
      functioning of vascular smooth muscle cells and fibroblasts, causing aberrant
      dedifferentiation and proliferation. Given the large amounts of foreign material
      inhaled, the lung is densely populated by various types of immune cells
      specialized in engulfing and killing pathogens and in secreting
      cytokines/chemokines for efficient microbial clearance. Unfolded protein response
      signaling cascades have been shown to intersect with the functioning of immune
      cells at all levels. The current review aims to highlight the role of ER stress
      in health and disease in the lung, focusing on its impact on different structural
      and inflammatory cell types.

PMID- 23536205
TI  - Introduction of a classification system for patients with patellofemoral
      instability (WARPS and STAID).
AB  - PURPOSE: The primary purpose of this paper is to introduce the WARPS/STAID
      classification system for patellofemoral instability. The secondary purpose is to
      establish the validity and reliability of the WARPS/STAID classification system.
      METHODS: Patients (n = 31) with a confirmed diagnosis of patellofemoral
      instability underwent a thorough knee history and physical examination with 3
      raters. The raters graded each component of the WARPS/STAID classification system
      on a visual analogue scale (VAS). A single Global VAS WARPS/STAID score was
      graded after all other components of the classification system were completed.
      Intraclass correlation coefficient (ICC 2, 3) was calculated for each metric of
      the classification scale and for the Global score. Concurrent validity was
      assessed by correlating the WARPS/STAID score with the Kujala score. Subjects
      were assigned to one of three categories (WARPS, STAID, or mixed characteristics)
      according to the Total WARPS/STAID score to determine the level of agreement
      between the three raters. RESULTS: Intraclass correlation coefficient (ICC 2, 3)
      of the WARPS/STAID classification continuum ranged between 0.73 and 0.91 for the
      individual metrics of the classification. The ICC (2, 3) for the Global
      WARPS/STAID score was 0.75. The mean Kujala score (m = 61, SD 18) was
      significantly correlated with the total WARPS/STAID score (r = 0.387, p < 0.05).
      The majority of subjects were assigned to either the WARPS or STAID categories.
      CONCLUSION: This study introduced the WARPS/STAID classification system and
      established both validity and reliability in subjects with patellofemoral
      instability. LEVEL OF EVIDENCE: II.

PMID- 23536206
TI  - Online monitoring of printed electronics by Spectral-Domain Optical Coherence
      Tomography.
AB  - Spectral-Domain Optical Coherence Tomography (SD-OCT) is an optical method
      capable of 3D imaging of object's internal structure with micron-scale
      resolution. Modern SD-OCT tools offer the speed capable of online monitoring of
      printed devices. This paper demonstrates the use of SD-OCT in a simulated roll-to
      roll (R2R) process through monitoring some structural properties of moving screen
      printed interdigitated electrodes. It is shown that structural properties can be
      resolved for speeds up to ca. 1 m/min, which is the first step towards
      application of this method in real manufacturing processes, including roll-to
      roll (R2R) printing.

PMID- 23536207
TI  - Influence of CYP2C8 polymorphisms on the hydroxylation metabolism of paclitaxel,
      repaglinide and ibuprofen enantiomers in vitro.
AB  - CYP2C8 plays an important role in the metabolism of various drugs, such as
      paclitaxel, repaglinide and ibuprofen. Polymorphisms in the CYP2C8 gene were
      shown to influence interindividual differences in the pharmacokinetics of
      paclitaxel, repaglinide and ibuprofen enantiomers. In this study, three CYP2C8
      allelic variants (CYP2C8.2, CYP2C8.3 and CYP2C8.4) and wild-type CYP2C8
      (CYP2C8.1) were co-expressed for the first time with human cytochrome P450
      oxidoreductase (POR) and cytochrome b5 by using a baculovirus-assisted insect
      cell expression system. Further, the effects of genotype-phenotype correlations
      of CYP2C8 alleles on the metabolism of paclitaxel, repaglinide and ibuprofen
      enantiomers were evaluated. The CLint values of CYP2C8.2, CYP2C8.3 and CYP2C8.4
      for paclitaxel were 47.7%, 64.3% and 30.2% of that of CYP2C8.1 (p<0.01). The
      CLint values of CYP2C8.2 and CYP2C8.4 for repaglinide were 77.9% and 80.2% of
      that of CYP2C8.1 (p<0.05), respectively, while the CLint value of CYP2C8.3 was
      1.31-fold higher than that of CYP2C8.1 (p<0.05). The relative CLint values of
      CYP2C8.2, CYP2C8.3 and CYP2C8.4 were 110.5%, 72.3% and 49.7% of that of CYP2C8.1
      and were 124.6%, 83.4% and 47.4% of that of CYP2C8.1 for R-ibuprofen and S
      ibuprofen, respectively. Comparing hydroxylation by CYP2C8.1 and CYP2C8.3
      resulted in higher and lower intrinsic clearance of repaglinide and ibuprofen
      enantiomers, respectively. These in vitro findings were consistent with the
      pharmacokinetics in volunteers who were heterozygous or homozygous carriers of
      CYP2C8*3. The results of this study provide useful information for predicting
      CYP2C8 phenotypes and may contribute to individualized drug therapy in the
      future.

PMID- 23536208
TI  - Polysaccharide-lecithin reverse micelles with enzyme-degradable triglyceride
      shell for overcoming tumor multidrug resistance.
AB  - A newly-designed drug carrier with enzyme-triggered release behavior and the
      ability to circumvent multidrug resistance was successfully developed. By
      optimizing the ratio of lecithin and polysaccharide in reverse micelles,
      encapsulation efficiency and encapsulation stability can be significantly
      improved.

PMID- 23536210
TI  - Cadmium, mercury, and lead in kidney cortex are not associated with urinary 8-oxo
      7,8-dihydro-2'-deoxyguanosine (8-oxodG) in living kidney donors.
AB  - PURPOSE: Cadmium in urine is positively associated with urinary 8-oxo-7,8-dihydro
      2'-deoxyguanosine (8-oxodG) concentrations, a sensitive marker of oxidative DNA
      damage. We determined whether kidney concentrations of cadmium, mercury, and
      lead, which may generate oxidative DNA damage, were associated with urinary 8
      oxodG or not. METHODS: 8-OxodG was measured in separate 24 h and overnight urine
      samples from Swedish healthy adult kidney donors (N = 152) using LC-MS/MS.
      Concentrations of metals were measured in kidney biopsies (N = 109) by ICP-MS.
      RESULTS: The median 8-oxodG concentrations (adjusted to specific gravity) in 24 h
      and overnight samples were 13.5 and 15.3 nmol/L; 8-oxodG excretion rates in 24 h
      and overnight samples were 0.93 and 0.86 nmol/h. In multivariable linear
      regression analyses, we did not find any association between 8-oxodG
      concentrations or rates and elements in the kidney. The 24-h 8-oxodG
      concentrations were positively associated with serum ferritin (beta = 0.048, p <
      0.0001), body weight (beta = 0.13, p = 0.0019), and inversely with gender (beta =
      -3.34, p = 0.0024). Similar associations with 8-oxodG excretion rates were
      stronger. Smoking was positively associated with 24-h 8-oxodG excretion rates
      (beta = 0.26, p = 0.0090), but not with overnight samples. CONCLUSIONS: Neither
      cadmium, nor mercury or lead in the kidney contributed to urinary 8-oxodG
      concentrations in non-occupationally exposed subjects. The iron status was
      positively associated with urinary 8-oxodG, particularly in women.

PMID- 23536211
TI  - Infants at risk for autism: a European perspective on current status, challenges
      and opportunities.
AB  - Currently, autism cannot be reliably diagnosed before the age of 2 years, which
      is why longitudinal studies of high-risk populations provide the potential to
      generate unique knowledge about the development of autism during infancy and
      toddlerhood prior to symptom onset. Early autism research is an evolving field in
      child psychiatric science. Key objectives are fine mapping of neurodevelopmental
      trajectories and identifying biomarkers to improve risk assessment, diagnosis and
      treatment. ESSEA (Enhancing the Scientific Study of Early Autism) is a COST
      (European Cooperation in Science and Technology) Action striving to create a
      European collaboration to enhance the progress of the discovery and treatment of
      the earliest signs of autism, and to establish European practice guidelines on
      early identification and intervention by bringing together European expertise
      from cognitive neuroscience and clinical sciences. The objective of this article
      is to clarify the state of current European research on at-risk autism research,
      and to support the understanding of different contexts in which the research is
      being conducted. We present ESSEA survey data on ongoing European high-risk ASD
      studies, as well as perceived challenges and opportunities in this field of
      research. We conclude that although high-risk autism research in Europe faces
      several challenges, the existence of several key factors (e.g., new and/or large
      scale autism grants, availability of new technologies, and involvement of
      experienced research groups) lead us to expect substantial scientific and
      clinical developments in Europe in this field during the next few years.

PMID- 23536212
TI  - Child and adolescent psychiatry in Belgium and the Flemish Association for Child
      and Adolescent Psychiatry.

PMID- 23536213
TI  - Synthesis and characterisation of bismuth(III) aminoarenesulfonate complexes and
      their powerful bactericidal activity against Helicobacter pylori.
AB  - The synthesis and characterisation of nine new tris-substituted bismuth(III)
      aminoarenesulfonates of the general formula [Bi(O3S-R(N))3] (R(N) = o-aminophenyl
      1, m-aminophenyl 2, 6-amino-3-methoxyphenyl 3, p-aminophenyl 4, 2-pyridyl 5, o
      aminonaphthyl 6, 5-aminonaphthyl 7, 4-amino-3-hydroxynaphthyl 8 and 5
      isoquinolinyl 9) is described. Two synthetic strategies, using Ag2O and
      [Bi(OtBu)3], were explored and compared. The possibility to access heteroleptic
      bismuth(III) complexes with the new silver(I) metathesis reaction is demonstrated
      with the synthesis of the heteroleptic bismuth(III) aminoarenesulfonate complexes
      [PhBi(O3S-P2)2(dmso)] 10, [Ph2Bi(O3S-P2)]infinity 11 and [PhBi(O3S-P2)2]infinity
      12, of which the solid state structures 10 and 12 are presented (2P-SO3(-) = 2
      pyridinesulfonate). These complexes offer remarkable in-vitro activity against
      three standard laboratory strains of Helicobacter pylori (H. pylori) as
      demonstrated by their exceptionally low minimum inhibitory concentration (MIC)
      values of 0.049 MUg  mL(-1) for the strains 251 and B128, which places most MIC
      values in the nano-molar region. These results demonstrate the importance of the
      amino functionality in addition to the sulfonate group on the bactericidal
      properties against H. pylori.

PMID- 23536214
TI  - Studying gene expression at the level of the single cell.

PMID- 23536215
TI  - Some remarks on predicting multi-label attributes in molecular biosystems.
AB  - Many molecular biosystems and biomedical systems belong to the multi-label
      systems in which each of their constituent molecules possesses one or more than
      one function or feature, and hence needs one or more than one label to indicate
      its attribute(s). With the avalanche of biological sequences generated in the
      post genomic age, it is highly desirable to develop computational methods to
      timely and reliably identify their various kinds of attributes. Compared with the
      single-label systems, the multi-label systems are much more complicated and
      difficult to deal with. The current mini review focuses on the recent progresses
      in this area from both conceptual aspects and detailed mathematical formulations.

PMID- 23536216
TI  - Asymmetric synthesis of carbocycles: use of intramolecular conjugate
      displacement.
AB  - Intramolecular conjugate displacement (ICD), the process illustrated in , has
      been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l
      menthyloxy)-2(5H)-furanone and aldehydes that are substituted in the gamma- or
      delta-position by geminal phenylthio groups. When the initial Morita-Baylis
      Hillman alcohols are acetylated and oxidized to geminal sulfones, deprotonation
      causes ring closure by ICD (2.5->2.6). Hydrogenation, DIBAL-H reduction and
      desulfonylation releases an optically pure carbocycle.

PMID- 23536217
TI  - Biocontrol of postharvest Rhizopus decay of peaches with Pichia caribbica.
AB  - A new yeast antagonist, Pichia caribbica, isolated in our laboratory from the
      soil collected from unsprayed orchards, was evaluated for its biocontrol
      capability against Rhizopus stolonifer on peaches and the possible mechanisms
      involved. The decay incidence and lesion diameter of Rhizopus decay of peaches
      treated by P. caribbica were significantly reduced compared with the control
      fruits, and the higher the concentration of P. caribbica, the better the efficacy
      of the biocontrol. Rapid colonization of the yeast in peach wounds stored at 25 
      degrees C was observed. In peaches, the activities of peroxidase (POD), catalase
      (CAT), and phenylalanine ammonia-lyase (PAL) were significantly induced by P.
      caribbica treatment compared to those of the control fruits. All these results
      indicated that P. caribbica has a great potential for the development of
      commercial formulations to control postharvest Rhizopus decay of peaches. Its
      modes of action were based on competition for space and nutrients with pathogens,
      inducement of activities of defense-related enzymes such as POD, CAT, and PAL of
      peaches. 

PMID- 23536218
TI  - Experimental study on the facilitative effects of miR-125b on the differentiation
      of rat bone marrow mesenchymal stem cells into neuron-like cells.
AB  - To observe the effects of miR-125b on the differentiation of rat bone marrow
      mesenchymal stem cells (BMSCs) into neuron-like cells, rat BMSCs were isolated
      and transfected with Syn-rno-miR-125b* miScript miRNA Mimic (Mimic + BME group),
      with anti-rno-miR-125b* miScript miRNA Inhibitor (Inhibitor + BME group) and BME
      control was set up without transfection. Blank controls without transfection and
      induction by BME was also set up. BMSCs of three groups including Mimic + BME
      group, Inhibitor + BME group and BME group were induced to differentiate into
      neuron-like cells by beta-mercaptoethanol (BME). Cells in the Blank group were
      not treated by BME. mRNA expression of miR-125b was determined with qRT-PCR in
      each group. mRNA and protein expressions of seven nerve cell markers, including
      beta3 tubulin, neural microtubule-associated protein (MAP-2), neurofilament
      protein (NF), neuron-specific enolase (NSE), glial fibrillary acidic protein
      (GFAP), Nestin and Vimentin in the four groups were determined by RT-PCR and
      Western blots. GFAP and Nestin were detected by immunofluorescent and
      immunocytochemistry assays. Compared with BME group, mRNA and protein expression
      of beta3 tubulin, MAP-2, NF, NSE, GFAP, Nestin were significantly increased in
      the Mimic + BME group (P < 0.01), but significantly decreased in the Inhibitor +
      BME group (P < 0.01). Cells in the Mimic + BME group were more like nerve cells
      in morphology than cells in the BME groups. Thus miR-125b can promote BME to
      induce rat BMSCs differentiation into neuron-like cells.

PMID- 23536219
TI  - Degradation of polyester polyurethane by a newly isolated soil bacterium,
      Bacillus subtilis strain MZA-75.
AB  - A polyurethane (PU) degrading bacterial strain MZA-75 was isolated from soil
      through enrichment technique. The bacterium was identified through 16S rRNA gene
      sequencing, the phylogenetic analysis indicated the strain MZA-75 belonged to
      genus Bacillus having maximum similarity with Bacillus subtilis strain JBE0016.
      The degradation of PU films by strain MZA-75 in mineral salt medium (MSM) was
      analyzed by scanning electron microscopy (SEM), fourier transform infra-red
      spectroscopy (FT-IR) and gel permeation chromatography (GPC). SEM revealed the
      appearance of widespread cracks on the surface. FTIR spectrum showed decrease in
      ester functional group. Increase in polydispersity index was observed in GPC,
      which indicates chain scission as a result of microbial treatment. CO2 evolution
      and cell growth increased when PU was used as carbon source in MSM in Sturm test.
      Increase in both cell associated and extracellular esterases was observed in the
      presence of PU indicated by p-Nitrophenyl acetate (pNPA) hydrolysis assay.
      Analysis of cell free supernatant by gas chromatography-mass spectrometry (GC-MS)
      revealed that 1,4-butanediol and adipic acid monomers were produced. Bacillus
      subtilis strain MZA-75 can degrade the soft segment of polyester polyurethane,
      unfortunately no information about the fate of hard segment could be obtained.
      Growth of strain MZA-75 in the presence of these metabolites indicated
      mineralization of ester hydrolysis products into CO2 and H2O. 

PMID- 23536220
TI  - Joint guidance on peptide receptor radionuclide therapy in neuroendocrine tumors.

PMID- 23536222
TI  - Being sensitive: to specify when amino acid tracers accumulate in a brain lesion.

PMID- 23536223
TI  - Molecular imaging of conscious, unrestrained mice with AwakeSPECT.
AB  - We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain
      imaging of untrained mice that are conscious, unanesthetized, and unrestrained.
      We accomplished this with head tracking and motion correction techniques.
      METHODS: The capability of the system for motion-corrected imaging was
      demonstrated with a (99m)Tc-pertechnetate phantom, (99m)Tc-methylene
      diphosphonate bone imaging, and measurement of the binding potential of the
      dopamine transporter radioligand (123)I-ioflupane in mouse brain in the awake and
      anesthetized (isoflurane) states. Stress induced by imaging in the awake state
      was assessed through measurement of plasma corticosterone levels. RESULTS:
      AwakeSPECT provided high-resolution bone images reminiscent of those obtained
      from CT. The binding potential of (123)I-ioflupane in the awake state was on the
      order of 50% of that obtained with the animal under anesthesia, consistent with
      previous studies in nonhuman primates. Levels of stress induced were on the order
      of those seen in other behavioral tasks and imaging studies of awake animals.
      CONCLUSION: These results demonstrate the feasibility of SPECT molecular brain
      imaging of mice in the conscious, unrestrained state and demonstrate the effects
      of isoflurane anesthesia on radiotracer uptake.

PMID- 23536224
TI  - Monitoring bone marrow stem cells with a reporter gene system in experimental
      middle cerebral artery occlusion rat models.
AB  - This study was designed to investigate the feasibility of imaging bone marrow
      stem cells (BMSCs) in experimental middle cerebral artery occlusion (MCAO) rat
      models with a reporter gene-probe system, HSV1-tk-(131)I-2'-fluoro-2'-deoxy-1
      beta-d-arabinofuranosyl-5-iodouracil ((131)I-FIAU), and to choose the best
      strategies for stem cell injection, image acquisition, and imaging in vivo.
      METHODS: A recombinant adenovirus (Ad5-TIBE) carrying the herpes simplex virus
      type 1 thymidine kinase (TK) reporter gene (HSV1-tk) linked via the internal
      ribosome entry site to the brain-derived neurotrophic factor therapeutic gene was
      prepared. After transfection with Ad5-TIBE, BMSCs were introduced into MCAO rat
      models via local injection into the brain or via injection into the lateral
      ventricle, carotid artery, and tail vein. Normal rats were used as controls.
      Twenty-four hours after (131)I-FIAU injection, rats were sacrificed for
      biodistribution analysis. The expression of the TK gene was evaluated by real
      time quantitative polymerase chain reaction and Western blot analysis.
      Autoradiography was used for ex vivo imaging. SPECT images were obtained in MCAO
      rat models. RESULTS: The percentage injected dose per gram (%ID/g) in infarcted
      brain tissue in rats receiving the injection into the brain was 0.124 +/- 0.013;
      this value was significantly higher than those in rats receiving the injection
      into the ventricle (0.052 +/- 0.004), carotid artery (0.061 +/- 0.002), and tail
      vein (0.059 +/- 0.005) as well as normal rats (0.005 +/- 0.001). No differences
      were seen in the other cell transplantation groups. The %ID/g in infarcted brain
      tissue was higher than that in the contralateral brain tissue in all experimental
      rats but not in normal rats. The expression of the TK gene in rats receiving a
      local injection into the brain was superior to that in all of the other groups.
      TK messenger RNA and protein expression showed a positive correlation with the
      %ID/g in brain tissue. Greater radioactivity at the injection site than in the
      surrounding and contralateral brain tissues in all experimental rats was
      indicated through autoradiography. The ratio of counts in bilateral brain tissues
      reached its peak (6.63) 24 h after (131)I-FIAU injection. SPECT images showed
      that radioactivity accumulation in the brain was low but increased gradually over
      time. CONCLUSION: The HSV1-tk-(131)I-FIAU reporter gene-probe system may be used
      to monitor BMSC activity in experimental MCAO rat models. Local injection of stem
      cells may provide an optimal means for cell transplantation, and imaging with
      (131)I-FIAU 24 h after injection provides peak target-to-nontarget count ratios.

PMID- 23536225
TI  - Acquisition protocols and correction methods for estimation of the heart-to
      mediastinum ratio in 123I-metaiodobenzylguanidine cardiac sympathetic imaging.
AB  - Septal penetration of high-energy photons affects quantitative results in imaging
      of (123)I-labeled tracers. We investigated acquisition protocols (collimator
      choice and energy window setting) and correction methods for estimating the heart
      to-mediastinum (H/M) ratio in cardiac (123)I-metaiodobenzylguanidine (MIBG)
      imaging. METHODS: Four hours after (123)I-MIBG injection, 40 patients
      successively underwent planar anterior chest imaging with the medium-energy (ME)
      (ME method) and low-energy high-resolution (LEHR) (LEHR method) collimators. A
      20% energy window was used for both collimators. Another 40 patients were imaged
      successively with the ME collimator and a 20% window (ME method), the low-medium
      energy (LME) collimator and a 20% window (LME20 method), and the LME collimator
      and a 15% window (LME15 method). The H/M ratios obtained by the LEHR, LME20, and
      LME15 methods were corrected using their correlations with the H/M ratio obtained
      by the ME method (empiric correction). The (123)I-dual-window (IDW) correction
      was also applied to remove the influence of high-energy photons. RESULTS: Without
      correction, severe underestimation of the H/M ratio was shown for the LEHR method
      using the ME method as a standard, and this underestimation increased with
      increasing H/M ratios. Underestimation substantially decreased using the LME20
      method and further using the LME15 method. Empiric correction reduced the error
      in the H/M ratio by the LEHR method, but the error was still evident. After
      empiric correction, the H/M ratios with the LME collimator were comparable to
      those with the ME collimator. The IDW correction only partially reduced
      underestimation by the LEHR method and caused a small overestimation for the
      LME15 method. CONCLUSION: The use of an LME collimator appears to be acceptable
      for cardiac (123)I-MIBG imaging as an alternative to an ME collimator, and the
      application of a 15% energy window is recommended when an LME collimator is used.
      Empiric correction is also expected to improve exchangeability between H/M ratios
      calculated with ME and LME collimators. Neither the use of an LEHR collimator nor
      the use of IDW correction is recommended.

PMID- 23536226
TI  - Acute cytotoxic effects of photoimmunotherapy assessed by 18F-FDG PET.
AB  - We have recently developed a cancer-specific therapy, photoimmunotherapy, which
      uses an antibody-IR700 (phototoxic phthalocyanine dye) conjugate to bind to the
      cell membrane and near-infrared light to induce immediate and highly specific
      tumor killing in vivo. For monitoring the acute cytotoxic effects of
      photoimmunotherapy before the tumor begins to shrink, we used (18)F-FDG PET
      before and after this intervention in mice. METHODS: Photoimmunotherapy was
      performed by binding panitumumab (anti-HER1)-IR700 to HER1-positive tumor cells
      (A431), followed by near-infrared light irradiation in vitro and in vivo. The
      uptake of (18)F-FDG in the tumor after photoimmunotherapy was evaluated in
      cellular uptake studies and PET imaging studies. Serial histologic analyses were
      conducted after photoimmunotherapy. RESULTS: The in vitro cellular uptake of
      (18)F-FDG was reduced as the dose of light increased, and at high light dose (2
      J/cm(2)) the uptake was reduced by more than 99% within 1 h after
      photoimmunotherapy. In vivo (18)F-FDG PET imaging showed that the accumulation of
      radioactivity in the treated tumors decreased 76% at 75 min after
      photoimmunotherapy and did not change for 24 h. In contrast, no significant
      changes were demonstrated in nontreated tumors. None of tumors changed size
      within 24 h after photoimmunotherapy, although diffuse necrosis was observed in
      photoimmunotherapy-treated tumors. CONCLUSION: Immediate cytotoxic effects
      induced by photoimmunotherapy were clearly detected by decreased glucose uptake
      using (18)F-FDG PET even before changes in tumor size became evident. (18)F-FDG
      allows the clinical assessment of the therapeutic effects of photoimmunotherapy
      earlier than anatomic methods that rely on tumor size.

PMID- 23536227
TI  - Correlation of pelvic organ prolapse staging with lower urinary tract symptoms,
      sexual dysfunction, and quality of life.
AB  - INTRODUCTION AND HYPOTHESIS: To evaluate the relationship between pelvic organ
      prolapse (POP) staging and clinical findings, lower urinary tract symptoms
      (LUTS), sexual dysfunction, and quality of life (QoL) using validated
      questionnaires. METHODS: Women attending the urogynecology unit with LUTS and/or
      bulging (n = 388) were grouped according to the POP quantification (POPQ). LUTS,
      sexual dysfunction, and QoL were evaluated using the Urinary Distress Inventory-6
      (UDI-6),the Overactive Bladder Awareness tool (OAB-V8), the Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), and the
      Incontinence Impact Questionnaire-7 (IIQ-7). Data regarding baseline
      characteristics, clinical findings, and scores of questionnaires were compared
      among the POP stages using the Kruskal-Wallis test. Pearson's and Spearman's
      correlation analyses were used to evaluate the correlation of POP staging with
      clinical findings, pelvic floor dysfunction related symptom severity, and QoL.
      RESULTS: According to the POPQ, patients were classified as: stage 0 (27.8 %),
      stage 1 (21.4%), stage 2 (38.9%), and stages 3 and 4 (11.8%). Irritative, stress,
      obstructive subscale scores of UDI-6 and physical, travel, emotional subscale
      scores of IIQ-7 were significantly different among POPQ stages. Weak correlations
      between POPQ staging and irritative, stress, obstructive subscale scores of UDI-6
      (r = 0.198, r = 0.192, and r = 0.146 respectively), and physical, travel, social,
      emotional subscale scores of IIQ-7 (r = 0.223, r = 0.154, r = 120 and r = 0.171
      respectively) were found (p < 0.05). Clinical findings (Q-tip and stress test
      positivity, post-void residual volumes) showed moderate to weak correlations with
      POPQ stages (r = 0.425, r = 0.117, r = 0.163 respectively; p < 0.05).
      CONCLUSIONS: The correlation of lower urinary tract dysfunction and POP staging
      was shown to be best represented by UDI-6 and IIQ-7.

PMID- 23536228
TI  - Interobserver variability when employing the IUGA/ICS classification system for
      complications related to prostheses and grafts in female pelvic floor surgery.
AB  - INTRODUCTION AND HYPOTHESIS: To unify and organize reporting, an International
      Urogynecological Association (IUGA)/International Continence Society (ICS) expert
      consortium published terminology guidelines with a classification system for
      complications related to implants used in female pelvic surgery. We hypothesize
      that the complexity of the codification system may be a hindrance to precision,
      especially with decreasing levels of postgraduate expertise. METHODS: Residents,
      fellows, and attending physicians were asked to code seven test cases taken from
      published literature. Category, timing, and site components of the classification
      system were assessed independently and according to the level of training.
      Interobserver reliability was calculated as percent agreement and Fleiss' kappa
      statistic. RESULTS: A total of 24 participants (6 attending physicians, 3
      fellows, and 15 residents) were tested. The percent agreement showed significant
      variation when classified by level of training. In all categories, attending
      physicians had the greatest percentage agreement and largest kappa. The most
      agreement was seen when attending physicians classified mesh complications by
      time, 71% agreement with kappa 0.73 [95% confidence interval (CI) 0.58-0.88]. For
      the same task, the percentage agreement for fellows was 57%, kappa 0.55 (95% CI
      0.23-0.87) and with residents 57%, kappa 0.71([95% CI 0.64-0.78). Interestingly,
      the site component of the classification system had the least overall agreement
      and lowest kappa [0%, kappa 0.29 (95% CI 0.26-0.32)] followed by the category
      component [14%, kappa 0.48 (95% CI 0.46-0.5)]. CONCLUSIONS: The IUGA/ICS mesh
      complication classification system has poor interobserver reliability. This
      trended downward with decreasing postgraduate level; however, we did not have
      sufficient statistical power to show an association when stratifying by all
      training levels. This highlights the complex nature of the classification system
      in its current form and its limitation for widespread clinical and research
      application.

PMID- 23536229
TI  - Intercellular and systemic spread of RNA and RNAi in plants.
AB  - Plants possess dynamic networks of intercellular communication that are crucial
      for plant development and physiology. In plants, intercellular communication
      involves a combination of ligand-receptor-based apoplasmic signaling, and
      plasmodesmata and phloem-mediated symplasmic signaling. The intercellular
      trafficking of macromolecules, including RNAs and proteins, has emerged as a
      novel mechanism of intercellular communication in plants. Various forms of
      regulatory RNAs move over distinct cellular boundaries through plasmodesmata and
      phloem. This plant-specific, non-cell-autonomous RNA trafficking network is also
      involved in development, nutrient homeostasis, gene silencing, pathogen defense,
      and many other physiological processes. However, the mechanism underlying
      macromolecular trafficking in plants remains poorly understood. Current progress
      made in RNA trafficking research and its biological relevance to plant
      development will be summarized. Diverse plant regulatory mechanisms of cell-to
      cell and systemic long-distance transport of RNAs, including mRNAs, viral RNAs,
      and small RNAs, will also be discussed.

PMID- 23536230
TI  - NADPH oxidase and aging drive microglial activation, oxidative stress, and
      dopaminergic neurodegeneration following systemic LPS administration.
AB  - Parkinson's disease is characterized by a progressive degeneration of substantia
      nigra (SN) dopaminergic neurons with age. We previously found that a single
      systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) injection caused a slow
      progressive loss of tyrosine hydroxylase immunoreactive (TH+IR) neurons in SN
      associated with increasing motor dysfunction. In this study, we investigated the
      role of NADPH oxidase (NOX) in inflammation-mediated SN neurotoxicity. A
      comparison of control (NOX2(+/+) ) mice with NOX subunit gp91(phox) -deficient
      (NOX2(-/-) ) mice 10 months after LPS administration (5 mg/kg, i.p.) resulted in
      a 39% (P < 0.01) loss of TH+IR neurons in NOX2(+/+) mice, whereas NOX2(-/-) mice
      did not show a significant decrease. Microglia (Iba1+IR) showed morphological
      activation in NOX2(+/+) mice, but not in NOX2(-/-) mice at 1 hr. Treatment of
      NOX2(+/+) mice with LPS resulted in a 12-fold increase in NOX2 mRNA in midbrain
      and 5.5-6.5-fold increases in NOX2 protein (+IR) in SN compared with the saline
      controls. Brain reactive oxygen species (ROS), determined using diphenyliodonium
      histochemistry, was increased by LPS in SN between 1 hr and 20 months.
      Diphenyliodonium (DPI), an NOX inhibitor, blocked LPS-induced activation of
      microglia and production of ROS, TNFalpha, IL-1beta, and MCP-1. Although LPS
      increased microglial activation and ROS at all ages studied, saline control
      NOX2(+/+) mice showed age-related increases in microglial activation, NOX, and
      ROS levels at 12 and 22 months of age. Together, these results suggest that NOX
      contributes to persistent microglial activation, ROS production, and dopaminergic
      neurodegeneration that persist and continue to increase with age.

PMID- 23536231
TI  - Lipophilic defenses from Alcyonium soft corals of Antarctica.
AB  - Alcyonacean soft corals lack physical or skeletal defenses and their nematocyst
      system is weak, leading to the conclusion that soft corals mainly rely on
      chemistry for protection from predators and microbes. Defensive chemicals of
      primary and secondary metabolic origin are exuded in the mucus surface layer,
      explaining the general lack of heavy fouling and predation in corals. In
      Antarctic ecosystems, where generalist predation is intense and mainly driven by
      invertebrate consumers, the genus Alcyonium is represented by eight species. Our
      goal was to investigate the understudied chemical ecology of Antarctic Alcyonium
      soft corals. We obtained six samples belonging to five species: A. antarcticum,
      A. grandis, A. haddoni, A. paucilobulatum, and A. roseum, and assessed the lipid
      soluble fractions for the presence of defensive agents in these specimens. Ethyl
      ether extracts were tested in feeding bioassays with the sea star Odontaster
      validus and the amphipod Cheirimedon femoratus as putative sympatric predators.
      Repellent activities were observed towards both consumers in all but one of the
      samples assessed. Moreover, three of the extracts caused inhibition to a
      sympatric marine bacterium. The ether extracts afforded characteristic illudalane
      sesquiterpenoids in two of the samples, as well as particular wax esters
      subfractions in all the colonies analyzed. Both kinds of metabolites displayed
      significant deterrent activities demonstrating their likely defensive role. These
      results suggest that lipophilic chemicals are a first line protection strategy in
      Antarctic Alcyonium soft corals against predation and bacterial fouling.

PMID- 23536232
TI  - Effects of diffusional kurtosis imaging parameters on diffusion quantification.
AB  - Diffusional kurtosis imaging (DKI) is a new technique based on non-Gaussian water
      diffusion analysis. However, the original DKI protocol (six b values and 30
      motion-probing gradient (MPG) directions) requires more than 10 min of scanning
      time, which is too long for daily clinical use. We aimed to find suitable b
      value, MPG direction, and diffusion time settings for faster DKI. Four normal
      healthy subjects participated in the study. All DKI data sets were acquired on a
      clinical 3T-MRI scanner (Philips Medical Systems) with use of three protocols of
      0-7500 s/mm(2) b values, 6-32 MPG directions, and 23-80 ms diffusion time. There
      was a remarkable difference in the standard deviation (SD) of the mean DK values
      in the number of MPG directions. The mean DK values were significantly higher in
      the posterior limb of the internal capsule (p = 0.003, r = 0.924) and thalamus (p
      = 0.005, r = 0.903), whereas the mean DK values of the cerebrospinal fluid (CSF)
      (p = 0.001, r = -0.976) were significantly lower when we used a longer diffusion
      time. Our results indicate that the SD of the mean DK values was higher in 15 MPG
      directions than in 20 MPG directions and more. Because the mean DK values of the
      CSF were significantly lower when we used longer diffusion times, we expect
      longer diffusion times to be useful for DKI. We propose the following imaging
      parameters for clinical use: 0, 1000, and 2000 s/mm(2) b values; 20 MPG
      directions; Delta/delta 45.3/13.3 ms.

PMID- 23536233
TI  - Insulin resistance and risk of cerebral infarction in a Japanese general
      population: the Jichi Medical School Cohort Study.
AB  - The aim of the study was to investigate the relation between insulin resistance
      and risk of cerebral infarction in a Japanese general population. The subjects
      were 2610 men and women without past history of stroke or myocardial infarction
      and who were under treatment for diabetes. Subjects were divided into quartiles
      by the homeostasis model assessment of insulin resistance (HOMA-IR), and Cox's
      proportional hazard model was used to calculate hazard ratios (HRs) for cerebral
      infarction. In men, the multivariate-adjusted HRs were 2.51 (95% confidence
      interval [CI] = 0.98-6.42) in quartile 1 (Q1), 1.43 (95% CI = 0.54-3.82) in Q2,
      and 2.13 (95% CI = 0.82-5.51) in Q4, using Q3 as the reference. In women, the
      multivariate-adjusted HRs were 2.12 (95% CI = 0.72-6.31) in Q1, 2.96 (95% CI =
      1.06-8.26) in Q3, and 2.31 (95% CI = 0.80-6.69) in Q4, using Q2 as the reference.
      The association between risk of cerebral infarction and HOMA-IR was not dose
      dependent. 

PMID- 23536234
TI  - High prevalence of HIV and syphilis among men who have sex with men recruited by
      respondent-driven sampling in a city in Eastern China.
AB  - Increasing prevalence of sexually transmitted diseases (STD) was reported among
      men who have sex with men (MSM) in China. A total of 407 MSMs were recruited by
      respondent-driven sampling (RDS) from May to July 2008 in Nanjing, China. Face-to
      face interviews were conducted to collect information on demographic and risk
      behaviors; blood samples were collected for HIV and syphilis antibodies testing.
      The adjusted HIV and syphilis prevalence were, respectively, 7.3% (confidence
      interval [CI] = 2.6%-10.2%) and 14.4% (95% CI = 9.3%-21.1%). Recruiting male sex
      partners mostly from saunas and receptive anal intercourse with men in the last 6
      months were independently associated with positive HIV status. Risk factors for
      positive syphilis status included being older than 28 years, low level of HIV
      related knowledge, having been a male sex worker, and having unprotected anal sex
      with casual male sex partners in the past 6 months. High HIV/STD prevalence was
      detected. HIV/STD prevention strategies are urgently warranted. 

PMID- 23536235
TI  - Blood pressure control among hypertensive patients with and without diabetes
      mellitus in six public primary care clinics in Malaysia.
AB  - Hypertension is a common comorbidity among diabetic patients. This study aimed to
      determine blood pressure (BP) control among hypertensive patients with and
      without diabetes. This was a cross-sectional study in 6 public primary care
      clinics in Wilayah Persekutuan, Malaysia. Hypertensive patients aged >=18 years
      and attending the clinics were selected via systematic random sampling. The BP
      control target was defined as <130/80 mm Hg for diabetic patients and <140/90 mm
      Hg for nondiabetic patients. A total of 1107 hypertensive patients participated
      in this study and 540 (48.7%) had diabetes. About one fourth (24.3%) of the
      hypertensive patients with diabetes achieved BP control target, compared with
      60.1% patients without diabetes (P < .001). Being diabetic and on >=2
      antihypertensive treatments were associated with poor BP control. Attention needs
      to be given to these groups of patients when managing patients with hypertension.

PMID- 23536236
TI  - Multidisciplinary perspective intervention with community involvement to decrease
      antibiotic sales in village groceries in Thailand.
AB  - In Thailand, antibiotics are rampantly available in village groceries, despite
      the fact that it is illegal to sell antibiotics without a pharmacy license. This
      study implemented a multidisciplinary perspectives intervention with community
      involvement (MPI&CI), which was developed based on information obtained from
      focus groups that included multidisciplinary stakeholders. Community leaders in
      the intervention group were trained to implement MPI&CI in their villages. A
      quasi-experiment with a pretest-posttest design was conducted. Data were
      collected from 20 villages in Mahasarakham Province (intervention group) along
      with another 20 villages (comparison group). Using a generalized linear mixed
      model Poisson regression with repeated measures, groceries in the intervention
      group had 87% fewer antibiotics available at postintervention compared with
      preintervention (relative rate = 0.13; 95% confidence interval = 0.07-0.23),
      whereas the control group had only an 8% reduction in antibiotic availability
      (relative rate = 0.92; 95% confidence interval = 0.88-0.97) between the 2 time
      periods. Further study should be made to assess the sustainability and long-term
      effectiveness of MPI&CI. 

PMID- 23536237
TI  - Review of physical activity prevalence of Asian school-age children and
      adolescents.
AB  - Overweight and obese populations in Asia are high and increasing rapidly.
      Physical activity prevalence studies have found low physical activity rates among
      Asian school-age children and adolescents. The purpose of this review is to
      establish a baseline for physical activity rates in Asian school-age children and
      adolescents and serve as a platform for additional research. Thirty articles
      published between 2000 and 2011 on physical activity prevalence of school-age
      children and adolescents were included in the review. Fourteen studies were
      conducted in East Asia, 10 in Southeast Asia, 2 in South Asia, and 2 in West
      Asia. Studies used subjective methods (questionnaires or diaries) and objective
      methods (accelerometers or heart rate monitors). Although nearly all studies
      found low physical activity levels, it was not possible to provide an accurate
      picture due to an absence of standardized, reliable, and economically viable
      measurement tools.

PMID- 23536238
TI  - Comorbidity as an independent risk factor in patients with cancer: an 8-year
      population-based study.
AB  - This study determined the prevalence of medical conditions in patients with
      cancer and their impact on outcome. We evaluated a cohort of 37,411 patients
      diagnosed with cancer between 2000 and 2008 in Taiwan, collecting the cancer
      diagnosis and chronic disease diagnoses. The severity of the comorbid condition
      was correlated with the cancer diagnosis and outcome. Overall, 71.9% of the study
      population had 1 or more comorbid conditions. Patients with none (n = 10 508), 1
      (n = 8881), 2 (n = 6583), and 3 or more (n = 11 439) comorbid conditions had
      mortality rates of 11.49%, 15.99%, 19.61%, and 29.39%, respectively. Older
      patients with comorbid conditions had a significantly higher chance of death.
      Dementia, heart disease, or cerebrovascular diseases were associated with the
      highest mortality. Cancer patients with comorbid conditions have a significantly
      higher risk of death. Prevention and better medical management of comorbid
      conditions is likely to result in improved outcomes for patients with cancer.

PMID- 23536239
TI  - Effectiveness of a large-scale health and nutritional education program on anemia
      in children younger than 5 years in Shifang, a heavily damaged area of Wenchuan
      earthquake.
AB  - This study aimed to explore an ideal way to prevent anemia among children younger
      than 5 years after disasters especially when health care facilities are not
      enough. A preliminary survey was carried out involving 13 065 children younger
      than 5 years. Pretested questionnaires were used for data collection and
      hemoglobin levels were measured. After 12-month intervention, the impact survey
      involving 2769 children was conducted. Results showed that there were some
      improvements both in feeding knowledge and practice related to anemia. The total
      prevalence of anemia decreased from 14.3% to 7.8% (P < .001), and the severity of
      anemia also declined. The hemoglobin concentration increased significantly from
      118.8 +/- 10.5 to 122.0 +/- 9.9 g/L (P < .001). Thus, health and nutritional
      education could be an ideal way to combat anemia after disasters especially in
      less developed areas with multiparty cooperation. The methods and experiences of
      this study may be well worth learning and implementing. 

PMID- 23536241
TI  - Protein conformational disorder and enzyme catalysis.
AB  - Though lacking a well-defined three-dimensional structure, intrinsically
      unstructured proteins are ubiquitous in nature. These molecules play crucial
      roles in many cellular processes, especially signaling and regulation.
      Surprisingly, even enzyme catalysis can tolerate substantial disorder. This
      observation contravenes conventional wisdom but is relevant to an understanding
      of how protein dynamics modulates enzyme function. This chapter reviews
      properties and characteristics of disordered proteins, emphasizing examples of
      enzymes that lack defined structures, and considers implications of structural
      disorder for catalytic efficiency and evolution. 

PMID- 23536240
TI  - A general reaction-diffusion model of acidity in cancer invasion.
AB  - We model the metabolism and behaviour of a developing cancer tumour in the
      context of its microenvironment, with the aim of elucidating the consequences of
      altered energy metabolism. Of particular interest is the Warburg Effect, a
      widespread preference in tumours for cytosolic glycolysis rather than oxidative
      phosphorylation for glucose breakdown, as yet incompletely understood. We examine
      a candidate explanation for the prevalence of the Warburg Effect in tumours, the
      acid-mediated invasion hypothesis, by generalising a canonical non-linear
      reaction-diffusion model of acid-mediated tumour invasion to consider additional
      biological features of potential importance. We apply both numerical methods and
      a non-standard asymptotic analysis in a travelling wave framework to obtain an
      explicit understanding of the range of tumour behaviours produced by the model
      and how fundamental parameters govern the speed and shape of invading tumour
      waves. Comparison with conclusions drawn under the original system--a special
      case of our generalised system--allows us to comment on the structural stability
      and predictive power of the modelling framework.

PMID- 23536242
TI  - Molecular belts.
AB  - Rigid hydrocarbon macrocycles with radially-oriented pi-systems and continuous
      conjugation have attracted great interest in recent years. These molecular belts
      have novel optoelectronic properties and host-guest behavior. Certain belts may
      also ultimately lead to a rational synthesis of carbon nanotubes. The high strain
      associated with the nonplanar, conjugated backbones requires the development of
      new synthetic methods, and clever synthetic design. Herein we describe the
      synthetic history and properties of these structurally simple but synthetically
      challenging molecules. 

PMID- 23536243
TI  - Parahydrogen Induced polarization by homogeneous catalysis: theory and
      applications.
AB  - The alignment of the nuclear spins in parahydrogen can be transferred to other
      molecules by a homogeneously catalyzed hydrogenation reaction resulting in
      dramatically enhanced NMR signals. In this chapter we introduce the involved
      theoretical concepts by two different approaches: the well known, intuitive
      population approach and the more complex but more complete density operator
      formalism. Furthermore, we present two interesting applications of PHIP employing
      homogeneous catalysis. The first demonstrates the feasibility of using PHIP
      hyperpolarized molecules as contrast agents in (1)H MRI. The contrast arises from
      the J-coupling induced rephasing of the NMR signal of molecules hyperpolarized
      via PHIP. It allows for the discrimination of a small amount of hyperpolarized
      molecules from a large background signal and may open up unprecedented
      opportunities to use the standard MRI nucleus (1)H for, e.g., metabolic imaging
      in the future. The second application shows the possibility of continuously
      producing hyperpolarization via PHIP by employing hollow fiber membranes. The
      continuous generation of hyperpolarization can overcome the problem of fast
      relaxation times inherent in all hyperpolarization techniques employed in liquid
      state NMR. It allows, for instance, the recording of a reliable 2D spectrum much
      faster than performing the same experiment with thermally polarized protons. The
      membrane technique can be straightforwardly extended to produce a continuous flow
      of a hyperpolarized liquid for MRI enabling important applications in natural
      sciences and medicine. 

PMID- 23536244
TI  - Non-catalytic regulation of gene expression by aminoacyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases (AARSs) are a group of essential and ubiquitous "house
      keeping" enzymes responsible for charging corresponding amino acids to their
      cognate transfer RNAs (tRNAs) and providing the correct substrates for high
      fidelity protein synthesis. During the last three decades, wide-ranging
      biochemical and genetic studies have revealed non-catalytic regulatory functions
      of multiple AARSs in biological processes including gene transcription, mRNA
      translation, and mitochondrial RNA splicing, and in diverse species from bacteria
      through yeasts to vertebrates. Remarkably, ongoing exploration of non-canonical
      functions of AARSs has shown that they contribute importantly to control of
      inflammation, angiogenesis, immune response, and tumorigenesis, among other
      critical physiopathological processes. In this chapter we consider the non
      canonical functions of AARSs in regulating gene expression by mechanisms not
      directly related to their enzymatic activities, namely, at the levels of mRNA
      production, processing, and translation. The scope of AARS-mediated gene
      regulation ranges from negative autoregulation of single AARS genes to gene
      selective control, and ultimately to global gene regulation. Clearly, AARSs have
      evolved these auxiliary regulatory functions that optimize the survival and well
      being of the organism, possibly with more complex regulatory mechanisms
      associated with more complex organisms. In the first section on transcriptional
      control, we introduce the roles of autoregulation by Escherichia coli AlaRS,
      transcriptional activation by human LysRS, and transcriptional inhibition by
      vertebrate SerRS. In the second section on translational control, we recapitulate
      the roles of GluProRS in translation repression at the initiation step, auto
      inhibition of E. coli thrS mRNA translation by ThrRS, and global translational
      arrest by phosphorylated human MetRS. Finally, in the third section, we describe
      the RNA splicing activities of mitochondrial TyrRS and LeuRS in Neurospora and
      yeasts, respectively. 

PMID- 23536246
TI  - Amino-acyl tRNA synthetases generate dinucleotide polyphosphates as second
      messengers: functional implications.
AB  - In this chapter we describe aminoacyl-tRNA synthetase (aaRS) production of
      dinucleotide polyphosphate in response to stimuli, their interaction with various
      signaling pathways, and the role of diadenosine tetraphosphate and diadenosine
      triphosphate as second messengers. The primary role of aaRS is to mediate
      aminoacylation of cognate tRNAs, thereby providing a central role for the
      decoding of genetic code during protein translation. However, recent studies
      suggest that during evolution, "moonlighting" or non-canonical roles were
      acquired through incorporation of additional domains, leading to regulation by
      aaRSs of a spectrum of important biological processes, including cell cycle
      control, tissue differentiation, cellular chemotaxis, and inflammation. In
      addition to aminoacylation of tRNA, most aaRSs can also produce dinucleotide
      polyphosphates in a variety of physiological conditions. The dinucleotide
      polyphosphates produced by aaRS are biologically active both extra- and intra
      cellularly, and seem to function as important signaling molecules. Recent
      findings established the role of dinucleotide polyphosphates as second
      messengers. 

PMID- 23536247
TI  - Direct brain control and communication in paralysis.
AB  - Despite considerable growth in the field of brain-computer or brain-machine
      interface (BCI/BMI) research reflected in several hundred publications each year,
      little progress was made to enable patients in complete locked-in state (CLIS) to
      reliably communicate using their brain activity. Independent of the invasiveness
      of the BCI systems tested, no sustained direct brain control and communication
      was demonstrated in a patient in CLIS so far. This suggested a more fundamental
      theoretical problem of learning and attention in brain communication with
      BCI/BMI, formulated in the extinction-of-thought hypothesis. While operant
      conditioning and goal-directed thinking seems impaired in complete paralysis,
      classical conditioning of brain responses might represent the only alternative.
      First experimental studies in CLIS using semantic conditioning support this
      assumption. Evidence that quality-of-life in locked-in-state is not as limited
      and poor as generally believed draise doubts that "patient wills" or "advanced
      directives"signed long-before the locked-in-state are useful. On the contrary,
      they might be used as an excuse to shorten anticipated long periods of care for
      these patients avoiding associated financial and social burdens. Current state
      and availability of BCI/BMI systems urge a broader societal discourse on the
      pressing ethical challenges associated with the advancements in neurotechnology
      and BCI/BMI research. 

PMID- 23536245
TI  - Architecture and metamorphosis.
AB  - When compared to other conserved housekeeping protein families, such as ribosomal
      proteins, during the evolution of higher eukaryotes, aminoacyl-tRNA synthetases
      (aaRSs) show an apparent high propensity to add new sequences, and especially new
      domains. The stepwise emergence of those new domains is consistent with their
      involvement in a broad range of biological functions beyond protein synthesis,
      and correlates with the increasing biological complexity of higher organisms.
      These new domains have been extensively characterized based on their evolutionary
      origins and their sequence, structural, and functional features. While some of
      the domains are uniquely found in aaRSs and may have originated from nucleic acid
      binding motifs, others are common domain modules mediating protein-protein
      interactions that play a critical role in the assembly of the multi-synthetase
      complex (MSC). Interestingly, the MSC has emerged from a miniature complex in
      yeast to a large stable complex in humans. The human MSC consists of nine aaRSs
      (LysRS, ArgRS, GlnRS, AspRS, MetRS, IleRS, LeuRS, GluProRS, and bifunctional
      aaRs) and three scaffold proteins (AIMP1/p43, AIMP2/p38, and AIMP3/p18), and has
      a molecular weight of 1.5 million Dalton. The MSC has been proposed to have a
      functional dualism: facilitating protein synthesis and serving as a reservoir of
      non-canonical functions associated with its synthetase and non-synthetase
      components. Importantly, domain additions and functional expansions are not
      limited to the components of the MSC and are found in almost all aaRS proteins.
      From a structural perspective, multi-functionalities are represented by multiple
      conformational states. In fact, alternative conformations of aaRSs have been
      generated by various mechanisms from proteolysis to alternative splicing and
      posttranslational modifications, as well as by disease-causing mutations.
      Therefore, the metamorphosis between different conformational states is connected
      to the activation and regulation of the novel functions of aaRSs in higher
      eukaryotes. 

PMID- 23536248
TI  - Cell debris self-immobilized thermophilic lipase: a biocatalyst for synthesizing
      aliphatic polyesters.
AB  - The paper explored the catalytic activity of a cell debris self-immobilized
      thermophilic lipase for polyester synthesis, using the ring-opening
      polymerization of epsilon-caprolactone as model. Effects of biocatalyst
      concentration, temperature, and reaction medium on monomer conversion and product
      molecular weight were systematically evaluated. The biocatalyst displayed high
      catalytic activity at high temperatures (70-90  degrees C), with 100 % monomer
      conversion. High monomer conversion values (>90 %) were achieved in both
      hydrophobic and hydrophilic solvents, and also in solvent-free system, with the
      exception of dichloromethane. Poly(epsilon-caprolactone) was obtained in 100 %
      monomer conversion, with a number-average molecular weight of 1,680 g/mol and a
      polydispersity index of 1.35 in cyclohexane at 70  degrees C for 72 h.
      Furthermore, the biocatalyst exhibited excellent operational stability, with
      monomer conversion values exceeding 90 % over the course of 15 batch reactions.

PMID- 23536250
TI  - Enzymatic biodiesel synthesis in semi-pilot continuous process in near-critical
      carbon dioxide.
AB  - A semi-pilot continuous process (SPCP) for enzymatic biodiesel synthesis
      utilizing near-critical carbon dioxide (NcCO2) as the reaction medium was
      developed with the aim of reducing the reaction time and alleviating the catalyst
      inhibition by methanol. Biodiesel synthesis was evaluated in both lab-scale and
      semi-pilot scale reactors (batch and continuous reactors). In a SPCP, the highest
      conversion (~99.9 %) in four and a half hours was observed when three-step
      substrate (methanol) addition (molar ratio [oil/methanol] = 1:1.3) was used and
      the reaction mixture containing enzyme (Lipozyme TL IM, 20 wt.% of oil) was
      continuously mixed (agitation speed = 300 rpm) at 30  degrees C and 100 bar in a
      CO2 environment. The biodiesel produced from canola oil conformed to the fuel
      standard (EU) even without additional downstream processing, other than glycerol
      separation and drying.

PMID- 23536251
TI  - A novel multifunctional alpha-amylase from the thermophilic fungus Malbranchea
      cinnamomea: biochemical characterization and three-dimensional structure.
AB  - A novel alpha-amylase (McAmyA) from the thermophilic fungus, Malbranchea
      cinnamomea was purified, characterized and crystallized in the present study.
      McAmyA was purified to apparent homogeneity with a molecular mass of 60.3 kDa on
      SDS-PAGE. The enzyme exhibited maximal activity at pH 6.5 and was stable within
      pH 5.0-10.0. It was most active at 65  degrees C and was stable up to 50  degrees
      C. McAmyA was capable of hydrolyzing amylose, starch, amylopectin, pullulan,
      cyclodextrins and maltooligosaccharides. The full-length cDNA of an alpha-amylase
      gene (McAmyA) from the strain was cloned. McAmyA consisted of a 1,476-bp open
      reading frame encoding 492 amino acids. It displayed the highest amino acid
      sequence homology (less than 60 %) with the reported alpha-amylases. The crystal
      structure of McAmyA was solved at a resolution of 2.25 A (PDB code 3VM7). The
      overall structure of McAmyA reveals three domains with ten alpha helices and 14
      beta strands, and the putative catalytic residues are positioned at domain A with
      somewhat different secondary structural circumstances compared with typical alpha
      amylases.

PMID- 23536252
TI  - Culture and differentiation of rat neural stem/progenitor cells in a three
      dimensional collagen scaffold.
AB  - A stable and fast method for constructing a neural-like tissue from rat neural
      stem/progenitor cells (rNS/PCs) based on three-dimensional (3D) collagen gel is
      described. First step, the collagen-embedded rNS/PCs expanded with the medium
      consisting of DMEM/F12/RPMI1640 (1:1:1) supplemented with EGF and bFGF was used
      to expand the cells in gel in 96-well plates until the average diameter of cell
      clusters was about 50-100 MUm with the cell density higher than 10(7) cells/mL.
      In the second step, the initial medium was replaced with NB/B-27 supplemented
      with bFGF and BDNF. The results show that cells in collagen presented neural-like
      morphology and maintained live cell rate around 82 % in neural network pattern at
      least for 42 days under static conditions. The cell-collagen constructs were
      detected by immunofluorescence and immunohistochemistry test after 42 days of
      culture, part of cells still maintained the character of rNS/PCs, and others
      differentiated into neurons, astrocytes, and oligodendrocytes. Our 3D neural-like
      tissue construct was similar to the neural tissue in morphology and cell
      compositions. They thus have a potential to be used for drug screening, detection
      of environment toxins, and replacement therapy.

PMID- 23536253
TI  - Opportunities and challenges for molecular chaperone modulation to treat protein
      conformational brain diseases.
AB  - A common pathological hallmark of protein-conformational brain diseases is the
      formation of disease-specific protein aggregates. In Alzheimer's disease, these
      are comprised of amyloid-beta and Tau as opposed to alpha-synuclein in
      Parkinson's disease and N-terminal fragments of mutant huntingtin in Huntington's
      disease. Most aggregates also sequester molecular chaperones, a protein family
      that assists in the folding, refolding, stabilization, and processing of client
      proteins, including misfolded proteins in brain diseases. Molecular chaperone
      modulation has achieved remarkable therapeutic effects in some cellular and
      preclinical animal models of protein-conformational diseases. This has raised
      hope for chaperone-based strategies to combat these diseases. Here, we review
      briefly the functional diversity and medical significance of molecular
      chaperones, their therapeutic potential, and common and specific challenges
      towards clinical application. 

PMID- 23536254
TI  - A conceptual and disease model framework for osteoporotic kyphosis.
AB  - This paper presents a multi-method research project to develop a conceptual
      framework for measuring outcomes in studies of osteoporotic kyphosis. The
      research involved literature research and qualitative interviews among clinicians
      who treat patients with kyphosis and among patients with the condition.
      INTRODUCTION: Kyphosis due to at least one vertebral compression fracture is
      prevalent among osteoporotic patients, resulting in well-documented symptoms and
      impact on functioning and well-being. A three-part study led to development of a
      conceptual measurement framework for comprehensive assessment of symptoms,
      impact, and treatment benefit for kyphosis. METHODS: A literature-based disease
      model (DM) was developed and tested with physicians (n = 10) and patients (n =
      10), and FDA guidelines were used to develop a final disease model and a
      conceptual framework. RESULTS: The DM included signs, symptoms, causes/triggers,
      exacerbations, and functional status associated with kyphosis. The DM was largely
      confirmed, but physicians and patients added several concepts related to impact
      on functioning, and some concepts were not confirmed and removed from the DM.
      CONCLUSIONS: This study confirms the need for more comprehensive assessment of
      health outcomes in kyphosis, as most current studies omit key concepts.

PMID- 23536256
TI  - Multimodal intervention to improve osteoporosis care in home health settings:
      results from a cluster randomized trial.
AB  - SUMMARY: We conducted a cluster randomized trial testing the effectiveness of an
      intervention to increase the use of osteoporosis medications in high-risk
      patients receiving home health care. The trial did not find a significant
      difference in medication use in the intervention arm. INTRODUCTION: This study
      aims to test an evidence implementation intervention to improve the quality of
      care in the home health care setting for patients at high risk for fractures.
      METHODS: We conducted a cluster randomized trial of a multimodal intervention
      targeted at home care for high-risk patients (prior fracture or physician
      diagnosed osteoporosis) receiving care in a statewide home health agency in
      Alabama. Offices throughout the state were randomized to receive the intervention
      or to usual care. The primary outcome was the proportion of high-risk home health
      patients treated with osteoporosis medications. A t test of difference in
      proportions was conducted between intervention and control arms and constituted
      the primary analysis. Secondary analyses included logistic regression estimating
      the effect of individual patients being treated in an intervention arm office on
      the likelihood of a patient receiving osteoporosis medications. A follow-on
      analysis examined the effect of an automated alert built into the electronic
      medical record that prompted the home health care nurses to deploy the
      intervention for high-risk patients using a pre-post design. RESULTS: There were
      11 offices randomized to each of the treatment and control arms; these offices
      treated 337 and 330 eligible patients, respectively. Among the offices in the
      intervention arm, the average proportion of eligible patients receiving
      osteoporosis medications post-intervention was 19.1 %, compared with 15.7 % in
      the usual care arm (difference in proportions 3.4 %, 95 % CI, -2.6 to 9.5 %). The
      overall rates of osteoporosis medication use increased from 14.8 % prior to
      activation of the automated alert to 17.6 % afterward, a nonsignificant
      difference. CONCLUSIONS: The home health intervention did not result in a
      significant improvement in use of osteoporosis medications in high-risk patients.

PMID- 23536255
TI  - The role of the gastrointestinal tract in calcium homeostasis and bone
      remodeling.
AB  - While skeletal biology was approached in a rather isolated fashion in the past,
      an increasing understanding of the interplay between extraskeletal organs and
      bone remodeling has been obtained in recent years. This review will discuss
      recent advances in the field that have shed light on how the gastrointestinal
      tract and bone relate to each other. In particular, the importance of the GI
      tract in maintaining calcium homeostasis and skeletal integrity will be reviewed
      as impaired gastric acid production represents a major public health problem with
      possible implications for sufficient calcium absorption. Osteoporosis, the most
      prevalent bone disease worldwide, is caused not only by intrinsic defects
      affecting bone cell differentiation and function but also by a large set of
      extrinsic factors including hormonal disturbances, malnutrition, and iatrogenic
      drug application. Given the skeletal requirements of calcium, amino acids, and
      energy for bone turnover and renewal, it is not surprising that the
      gastrointestinal (GI) tract is of major importance for skeletal integrity. 

PMID- 23536257
TI  - The views of Pakistani doctors regarding genetic counseling services - is there a
      future?
AB  - Pakistan is a densely populated country in South Asia with a high burden of
      genetic disease. A dearth of medical genetic services exists and master's level
      trained genetic counselors (GCs) are currently not a part of the healthcare
      system. This study is the first to determine the views of Pakistani medical
      doctors (MDs) towards genetic counseling services in Pakistan, including what
      manner a master's level genetic counselor might be incorporated into the
      healthcare system. Fifty-one MDs practicing in the city of Karachi completed a
      self-administered survey of twenty questions. Of the 49 respondents who answered
      a specific question, 100 % (49/49) felt that they would refer at least some, if
      not all, of their relevant patients to a genetic's clinic if one existed in
      Karachi. Overall, the respondents showed a positive attitude towards the
      provision of genetic counseling services as a part of the healthcare system of
      Pakistan. Some of the proposed roles identified specifically for GCs included:
      explaining how Down syndrome occurs (66.1 %), discussing genes associated with
      breast cancer (77.4 %), and explaining the inheritance pattern of beta
      thalassemia (65.5 %). In contrast, the review of medical and family history and
      discussion of medical procedures such as ultrasound and amniocentesis were
      typically seen as the role of a physician. A majority of the respondents (98 %)
      were in favor of premarital carrier screening for thalassemia and would refer
      patients to a GC to describe the importance of carrier screening (84.3 %) and to
      help explain carrier screening results (94.1 %). Many respondents selected GCs as
      the ideal provider of education and support for people with inherited conditions
      (43.8 %), followed by specialist MDs (26 %) and general physicians (22.9 %).
      Considering the high burden of genetic disease in the country, we encourage the
      development of genetic counseling services in Pakistan. 

PMID- 23536258
TI  - Receiving enzyme replacement therapy for a lysosomal storage disorder: a
      preliminary exploration of the experiences of young patients and their families.
AB  - Medical intervention for lysosomal storage disorders becomes part of life,
      shaping the reality of the condition for affected individuals and families.
      Enzyme replacement therapy (ERT) is available to treat some lysosomal storage
      disorders. ERT is costly and time consuming, requiring frequent hospital visits
      to receive intravenous infusions. This qualitative study sought to explore the
      impact of receiving ERT for a lysosomal storage disorder on the health related
      quality of life (HRQoL) of young patients and their families. Fifteen semi
      structured interviews were conducted with young people and parents and siblings
      of young people accessing ERT for Pompe disease, Gaucher disease or
      mucopolysaccharidosis types I or II living in Victoria, Australia. Interviews
      were transcribed then analyzed thematically. The biopsychosocial model assisted
      in interpreting themes. Findings revealed positive attitudes towards ERT, with
      noticed improvements in physical and psychosocial well-being. Participants
      prioritised intervention over other activities and provided suggestions for
      improving current service delivery. Communication with family members and
      professionals was deemed important, especially in respect to information
      provision. Participants described challenges associated with living with a
      lysosomal storage disorder and receiving ERT and coping strategies, such as
      positive thinking and ways to manage uncertainty. These findings provide valuable
      insights into the impact of living with a chronic genetic condition and receiving
      intensive treatment on HRQoL. 

PMID- 23536259
TI  - Physical activity and sedentary time in persons with obstructive sleep apnea and
      overweight enrolled in a randomized controlled trial for enhanced physical
      activity and healthy eating.
AB  - BACKGROUND: The aim of the study was to describe the amount of physical activity
      and sedentary time in patients with obstructive sleep apnea syndrome (OSAS) and
      overweight and to explore potential disease-related and psychological correlates.
      METHODS: A descriptive and correlational study was performed. Prospective data of
      physical activity and sedentary time were collected through accelerometry, and
      body mass index (BMI), daytime sleepiness, exercise self-efficacy, fear of
      movement, and depressive symptoms were measured at one point. Seventy-three
      participants with overweight (mean BMI, 35 kg/m(2) (5 SD)) and moderate/severe
      OSAS (apnea-hypopnea index >=15) were consecutively recruited. Multivariate
      associations were determined through multiple linear regression analysis.
      RESULTS: The participants took a daily average of 7,734 (3,528 SD) steps, spent
      an average of 77 min (54 SD) in moderate-to-vigorous physical activity (MVPA),
      and spent 11 h and 45 min (2 h and 8 min SD) sedentary. BMI, daytime sleepiness,
      exercise self-efficacy, fear of movement, and depressive symptoms did not explain
      variance in MVPA or steps but explained 22.9 % of variance in sedentary time. In
      backward selection analysis, BMI contributed to the explanatory degree of MVPA
      with 9 % whereas, fear of movement explained 6.3 % of the variance in steps and
      14.3 % of the variance in sedentary time. CONCLUSIONS: An important implication
      for future physical activity interventions is that both physical activity and
      sedentary behaviors should be targeted, and fear of movement may be an important
      determinant for change in patients with OSAS and overweight.

PMID- 23536260
TI  - Obstructive sleep apnea syndrome (OSAS) in children with Class III malocclusion:
      involvement of the PHOX2B gene.
AB  - PURPOSE: The aim of this study is to provide new molecular approaches to the
      children with obstructive sleep apnea syndrome by evaluating the possible
      involvement of the PHOX2B gene, notoriously associated to congenital central
      hypoventilation syndrome (CCHS), in Class III malocclusion. METHODS: Fifty
      subjects with Class III malocclusion, aged from 8 to 14 years, and with history
      of sleep apneic episodes, and 20 age-matched controls were submitted to genomic
      DNA examination from oral cells to specifically analyze the PHOX2B genotype.
      RESULTS: Point "silent" mutations affecting different nucleotides of the PHOX2B
      gene were observed in 32 % of patients with Class III malocclusion and never in
      controls (0 %). CONCLUSION: The genetic data obtained in this study in children
      with Class III malocclusion and sleep-related breathing disorders provide new
      information useful to the genetic characterization of this pathology. The PHOX2B
      gene silent mutations can lead to structural and functional modification of their
      product providing to a group of children with Class III malocclusion similar
      features to those of CCHS (sleep apnea episodes and craniofacial malformations).

PMID- 23536261
TI  - Dynamics of predominant microbiota in the human gastrointestinal tract and change
      in luminal enzymes and immunoglobulin profile during high-altitude adaptation.
AB  - High-altitude (HA) visitors like pilgrims, trackers, scientists and military
      personnel face a group of nonspecific gastrointestinal (GI) symptoms during
      acclimatization to hypobaric hypoxia. In order to investigate the alteration of
      indigenous gastrointestinal microbiota in the development of such GI symptoms, an
      experiment was conducted for the enumeration of dominant cultivable faecal
      microbiota of 15 soldiers at base level (Delhi) and during their 15-day
      acclimatization at 3,505 m HA (Leh). At HA, faecal microbiota analysis revealed
      that total aerobes decreased significantly with increase of total and facultative
      anaerobes. The strict anaerobes like Bifidobacterium sp., Bacteroidetes sp. and
      Lactobacillus sp. exhibited positive growth direction index (GDI) like other
      predominant obligate anaerobes Clostridium perfringens and Peptostreptococcus sp.
      Different enzymes like amylase, proteinase and polyphenol hydrolase produced by
      different bacterial populations showed positive GDI, whereas phosphatase
      producers exhibited negative GDI. The levels of microbe-originated enzymes like
      amylase, proteinase, alkaline phosphatase and beta-glucuronidase were also
      elevated during HA acclimatization. In addition, in vitro gas production ability
      was enhanced with increase of faecal immunoglobulins IgA and IgG. We demonstrated
      that hypoxic environment at HA had the potential to alter the gut microbial
      composition and its activities that may cause GI dysfunctions. 

PMID- 23536262
TI  - Emotional attention modulates microsaccadic rate and direction.
AB  - Involuntary microsaccades and voluntary saccades reflect human brain activities
      during attention and cognitive tasks. Our eye movements can also betray our
      emotional state. However, the effects of attention to emotion on microsaccadic
      activity remain unknown. The present study was conducted in healthy volunteers to
      investigate the effects of devoting attention to exogenous emotional stimuli on
      microsaccadic response, with change in pupil size as an index of sympathetic
      nervous system activity. Event-related responses to unpleasant images
      significantly inhibited the rate of microsaccade appearance and altered pupil
      size (Experiment 1). Additionally, microsaccadic responses to covert orienting of
      attention to emotional stimuli appeared significantly in the anti-direction to a
      target, with a fast reaction time (Experiment 2). Therefore, we concluded that
      attentional shifts induced by exogenous emotional stimuli can modulate
      microsaccadic activities. Future studies of the interaction between miniature eye
      movements and emotion may be beneficial in the assessment of pathophysiological
      responses in mental disorders. 

PMID- 23536263
TI  - Adaptation of the "ten questions" to screen for autism and other
      neurodevelopmental disorders in Uganda.
AB  - Neurodevelopmental disorders are recognized to be relatively common in developing
      countries but little data exist for planning effective prevention and
      intervention strategies. In particular, data on autism spectrum disorders are
      lacking. For application in Uganda, we developed a 23-question screener (23Q)
      that includes the Ten Questions screener and additional questions on autism
      spectrum disorder behaviors. We then conducted household screening of 1169
      children, 2-9 years of age, followed by clinical assessment of children who
      screened positive and a sample of those who screened negative to evaluate the
      validity of the screener. We found that 320 children (27% of the total) screened
      positive and 68 children received a clinical diagnosis of one or more moderate to
      severe neurodevelopmental disorders (autism spectrum disorder; cerebral palsy;
      epilepsy; cognitive, speech and language, hearing, or vision impairment),
      including 8 children with autism spectrum disorders. Prevalence and validity of
      the screener were evaluated under different statistical assumptions. Sensitivity
      of the 23Q ranged from 0.55 to 0.80 and prevalence for >=1 neurodevelopmental
      disorders from 7.7/100 children to 12.8/100 children depending on which
      assumptions were used. The combination of screening positive on both autism
      spectrum disorders and Ten Questions items was modestly successful in identifying
      a subgroup of children at especially high risk of autism spectrum disorders. We
      recommend that autism spectrum disorders and related behavioral disorders be
      included in studies of neurodevelopmental disorders in low-resource settings to
      obtain essential data for planning local and global public health responses. 

PMID- 23536264
TI  - Biomarkers of lead exposure among a population under environmental stress.
AB  - This study aimed to evaluate the relationship between blood lead and serum
      creatinine and blood lead and serum urea nitrogen levels as biomarkers of lead
      exposure from subjects living in a historic polymetallic mining area in China.
      Elevated levels were found for blood lead, serum creatinine, and serum urea
      nitrogen in the mining area with mean values at 245.65 MUg/l, 74.16 MUmol/l, and
      12.79 mmol/l, which were significantly higher than those in the control area,
      respectively. Moreover, the coefficients between paired results for blood lead
      and serum creatinine and blood lead and serum urea nitrogen were positively
      statistically significant (serum creatinine vs. blood lead, r = 0.35, p < 0.05;
      serum urea nitrogen vs. blood lead, r = 0.48, p < 0.05). With respect to the
      effects of sex and age on the blood lead, serum creatinine, and serum urea
      nitrogen levels, data analysis revealed there was a tendency for higher blood
      lead, serum creatinine, and serum urea nitrogen levels in females than in males,
      and the levels of blood lead, serum creatinine, and serum urea nitrogen increased
      among older residents. We conclude that females and the older population in the
      mining area are more susceptible to lead exposure. Blood lead, serum creatinine,
      and serum urea nitrogen can be useful biomarkers of lead exposure among
      populations under environmental stress.

PMID- 23536265
TI  - Nonculprit coronary plaque characteristics of chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) promotes the development of
      atherosclerosis and increases the risk of cardiovascular disease. The aim of the
      present study was to compare the coronary plaque characteristics of patients with
      and without CKD using optical coherence tomography. METHODS AND RESULTS: We
      identified 463 nonculprit plaques from 287 patients from the Massachusetts
      General Hospital (MGH) optical coherence tomography registry. CKD was defined as
      estimated glomerular filtration rate <60 mL/min per 1.73 m(2). A total of 402
      plaques (250 patients) were in the non-CKD group and 61 plaques (37 patients)
      were in the CKD group. Compared with non-CKD plaques, plaques with CKD had a
      larger lipid index (mean lipid arc*lipid length, 1248.4+/-782.8 mm degrees  [non
      CKD] versus 1716.1+/-1116.2 mm degrees  [CKD]; P=0.003). Fibrous cap thickness
      was not significantly different between the groups. Calcification (34.8% [non
      CKD] versus 50.8% [CKD]; P=0.041), cholesterol crystals (11.2% [non-CKD] versus
      23.0% [CKD]; P=0.048), and plaque disruption (5.5% [non-CKD] versus 13.1% [CKD];
      P=0.049) were more frequently observed in the CKD group. In the multivariate
      linear regression model, a lower estimated glomerular filtration rate and
      diabetes mellitus were independent risk factors for a larger lipid index.
      CONCLUSIONS: Compared with non-CKD patients, the patients with CKD had a larger
      lipid index with a higher prevalence of calcium, cholesterol crystals, and plaque
      disruption. The multivariate linear regression model demonstrated that a lower
      estimated glomerular filtration rate was an independent risk factor for a larger
      lipid index.

PMID- 23536266
TI  - Cardiac-selective expression of extracellular superoxide dismutase after systemic
      injection of adeno-associated virus 9 protects the heart against post-myocardial
      infarction left ventricular remodeling.
AB  - BACKGROUND: Cardiac magnetic resonance imaging has not been used previously to
      document the attenuation of left ventricular (LV) remodeling after systemic gene
      delivery. We hypothesized that targeted expression of extracellular superoxide
      dismutase (EcSOD) via the cardiac troponin-T promoter would protect the mouse
      heart against both myocardial infarction (MI) and subsequent LV remodeling.
      METHODS AND RESULTS: Using reporter genes, we first compared the specificity,
      time course, magnitude, and distribution of gene expression from adeno-associated
      virus (AAV) 1, 2, 6, 8, and 9 after intravenous injection. The troponin-T
      promoter restricted gene expression largely to the heart for all AAV serotypes
      tested. AAV1, 6, 8, and 9 provided early-onset gene expression that approached
      steady-state levels within 2 weeks. Gene expression was highest with AAV9, which
      required only 3.15*10(11) viral genomes per mouse to achieve an 84% transduction
      rate. AAV9-mediated, cardiac-selective gene expression elevated EcSOD enzyme
      activity in heart by 5.6-fold (P=0.015), which helped protect the heart against
      both acute MI and subsequent LV remodeling. In acute MI, infarct size in EcSOD
      treated mice was reduced by 40% compared with controls (P=0.035). In addition, we
      found that cardiac-selective expression of EcSOD increased myocardial capillary
      fractional area and decreased neutrophil infiltration after MI. In a separate
      study of LV remodeling, after a 60-minute coronary occlusion, cardiac magnetic
      resonance imaging revealed that LV volumes at days 7 and 28 post-MI were
      significantly lower in the EcSOD group compared with controls. CONCLUSIONS:
      Cardiac-selective expression of EcSOD from the cardiac troponin-T promoter after
      systemic administration of AAV9 provides significant protection against both
      acute MI and LV remodeling.

PMID- 23536269
TI  - MSiReader: an open-source interface to view and analyze high resolving power MS
      imaging files on Matlab platform.
AB  - During the past decade, the field of mass spectrometry imaging (MSI) has greatly
      evolved, to a point where it has now been fully integrated by most vendors as an
      optional or dedicated platform that can be purchased with their instruments.
      However, the technology is not mature and multiple research groups in both
      academia and industry are still very actively studying the fundamentals of
      imaging techniques, adapting the technology to new ionization sources, and
      developing new applications. As a result, there important varieties of data file
      formats used to store mass spectrometry imaging data and, concurrent to the
      development of MSi, collaborative efforts have been undertaken to introduce
      common imaging data file formats. However, few free software packages to read and
      analyze files of these different formats are readily available. We introduce here
      MSiReader, a free open source application to read and analyze high resolution MSI
      data from the most common MSi data formats. The application is built on the
      Matlab platform (Mathworks, Natick, MA, USA) and includes a large selection of
      data analysis tools and features. People who are unfamiliar with the Matlab
      language will have little difficult navigating the user-friendly interface, and
      users with Matlab programming experience can adapt and customize MSiReader for
      their own needs.

PMID- 23536267
TI  - Prognostic value of cardiac time intervals by tissue Doppler imaging M-mode in
      patients with acute ST-segment-elevation myocardial infarction treated with
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Color tissue Doppler imaging M-mode through the mitral leaflet is an
      easy and precise method to estimate all cardiac time intervals from 1 cardiac
      cycle and thereby obtain the myocardial performance index (MPI). However, the
      prognostic value of the cardiac time intervals and the MPI assessed by color
      tissue Doppler imaging M-mode through the mitral leaflet in patients with ST
      segment-elevation myocardial infarction (MI) is unknown. METHODS AND RESULTS: In
      total, 391 patients were admitted with an ST-segment-elevation MI, treated with
      primary percutaneous coronary intervention, and examined by echocardiography a
      median of 2 days after the ST-segment-elevation MI. Outcome was assessed
      according to death (n=33), hospitalization with heart failure (n=53), or new MI
      (n=25). Follow-up time was a median of 25 months. The population was stratified
      according to tertiles of the MPI. The risk of new MI, being admitted with
      congestive heart failure or death, increased with increasing tertile of MPI,
      being ~3 times as high for the third tertile compared with the first tertile
      (hazard ratio, 2.8; 95% confidence interval, 1.7-4.7; P<0.001). MPI provided
      independent prognostic information in a multivariable Cox regression model
      adjusted for age, sex, previous MI, peak troponin, and systolic and diastolic
      echocardiographic parameters, with a hazard ratio of 1.24 (P=0.005) for the
      combined end point per each 0.1 increase in MPI. CONCLUSIONS: MPI assessed by
      tissue Doppler imaging M-mode is a simple and reproducible measure that provides
      independent prognostic information, regardless of rhythm, incremental to
      conventional and novel echocardiographic parameters of systolic and diastolic
      function in patients with ST-segment-elevation MI treated with primary
      percutaneous coronary intervention.

PMID- 23536270
TI  - Robert J. Cotter (1943-2012).

PMID- 23536271
TI  - beta-Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK
      pathway.
AB  - beta-Ionone is an end ring analog of beta-carotenoid which has been shown to
      possess potent anti-proliferative activity both in vitro and in vivo. To
      investigate the possible inhibitory effects of beta-ionone, we studied cell
      growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen
      activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma
      cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis
      were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose
      dependent manner in cells treated with beta-ionone (25, 50, 100 and 200 MUmol/L)
      for 24 h. We found that the beta-ionone significantly decreased the extracellular
      signal-regulated kinase protein expression and significantly increased the levels
      of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). beta-Ionone
      also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased
      p27 protein expression in SGC-7901 cells. These results suggested that the cell
      cycle arrest observed may be regulated through a MAPK pathway by transcriptional
      down-regulation of cell cycle proteins. These results demonstrate potent ability
      of beta-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation.

PMID- 23536272
TI  - Identification and quantitative detection of Legionella spp. in various aquatic
      environments by real-time PCR assay.
AB  - In this study, a SYBR green quantitative real-time PCR was developed to quantify
      and detect the Legionella spp. in various environmental water samples. The water
      samples were taken from watershed, water treatment plant, and thermal spring area
      in Taiwan. Legionella was detected in 13.6 % (24/176), and the detection rate for
      river water, raw drinking water, and thermal spring water was 10, 21.4, and 16.6
      %, respectively. Using real-time PCR, concentration of Legionella spp. in
      detected samples ranged between 9.75 * 10(4) and 3.47 * 10(5) cells/L in river
      water, 6.92 * 10(4) and 4.29 * 10(5) cells/L in raw drinking water, and 5.71 *
      10(4) and 2.12 * 10(6) cells/L for thermal spring water samples. The identified
      species included Legionella pneumophila (20.8 %), Legionella jordanis (4.2 %),
      Legionella nautarum (4.2 %), Legionella sp. (4.2 %), and uncultured Legionella
      sp. (66.6 %). The presence of L. pneumophila in aquatic environments suggested a
      potential public health threat that must be further examined. 

PMID- 23536273
TI  - Factors determining the fluctuation of fluoride concentrations in PM10 aerosols
      in the urbanized coastal area of the Baltic Sea (Gdynia, Poland).
AB  - Fluoride concentrations were determined in PM10 samples collected in the
      urbanized coastal area of the Baltic Sea (Gdynia) in the period between 1 August
      2008 and 8 January 2010. F(-) concentrations remained within the range of 0.4
      36.6 ng . m(-3). The economic transformations which have taken place in Poland
      increasing ecological awareness have had an excellent effect on the levels of
      fluoride pollution in the air of the studied region. In our measurements,
      fluoride concentrations increased in wintertime, when air temperature dropped, at
      low wind speeds (<1 m . s(-1)) and with low dispersion of pollutants originating
      from local sources (traffic, industry, domestic heating). At times when wind
      speed grew to >10 m . s(-1), fluorides were related to marine aerosols or else
      brought from distant sources. Apart from wind speed and air temperature, other
      significant meteorological parameters which determined the variability of F(-)
      turned out to be air humidity and precipitation volume. Aerosols were washed out
      effectively, even with small precipitation (h = 4 mm), and if a dry period lasted
      for several days, their concentrations grew rapidly to over 30.0 ng . m(-3). 

PMID- 23536274
TI  - Soy proteins as environmentally friendly sizing agents to replace poly(vinyl
      alcohol).
AB  - An environmentally friendly and inexpensive substitute to the widely used
      poly(vinyl alcohol) (PVA) has been developed from soy proteins for textile warp
      sizing. Textile processing is the major source of industrial water pollution
      across the world, and sizing and desizing operations account for nearly 30 % of
      the water consumed in a textile plant. PVA is one of the most common sizing
      agents used for synthetic fibers and their blends due to PVA's easy water
      solubility and ability to provide desired sizing performance. However, PVA does
      not degrade and is a major contributor to pollution in textile effluent treatment
      plants. Although considerable efforts have been made to replace PVA with
      biodegradable sizing materials, the performance properties provided by PVA on
      synthetic fibers and their blends have been unmatched so far. Soy proteins are
      inexpensive, biodegradable, and have been widely studied for potential use in
      food packaging, as resins and adhesives. In this research, the potential of using
      soy proteins as textile sizing agents to replace PVA was studied. Polyester and
      polyester/cotton rovings, yarns, and fabrics sized with soy protein showed a
      considerably better improvement in strength and abrasion resistance compared to
      commercially available PVA-based size. Soy protein size had a 5-day biochemical
      oxygen demand /chemical oxygen demand ratio of 0.57 compared to 0.01 for PVA
      indicating that soy protein sizes were easily biodegradable in activated sludge.
      The total and ammonia nitrogen released from the proteins also did not adversely
      impact the biodegradability. Good sizing performance and easy biodegradability
      demonstrate that soy protein-based sizes have potential to replace PVA-based
      sizes leading to substantial benefits to the textile industry and the
      environment. 

PMID- 23536275
TI  - Dissolved heavy metals in the Tigris River (Turkey): spatial and temporal
      variations.
AB  - Multivariate statistical techniques, such as analysis of variance, cluster
      analysis (CA), correlation analysis, principal component analysis (PCA), and
      factor analysis (FA), were applied to determine the spatial and temporal
      variations of dissolved heavy metals in the Tigris River at 7 different sites
      spread over the river stretch of about 500 km during the period of February 2008
      to January 2009. The results indicated that Fe, Cr, and Ni were the most abundant
      elements in the river water, whereas Cd and As were the less abundant. Cu, Fe,
      Ni, and Zn showed significant spatial variations, reflecting the influence of
      anthropogenic activities. The lowest total concentration of heavy metals was
      found at site 2 downstream of the Dicle Dam due to clean water from the dam. The
      concentrations of most metals were found lower when compared with results of
      previous studies due to reduction of the activity of the copper mine plant and
      the construction of two dams on the river. The lowest total concentrations were
      determined in February due to high precipitation and snow melts. Hierarchical
      agglomerative CA classified all the sampling sites into three main groups of
      spatial similarities. Clusters 1 (Maden and Bismil), 2 (Cizre), and 3 (Egil,
      Diyarbakir, Batman, and Hasankeyf) corresponded to moderate polluted and
      relatively low polluted regions, respectively. PCA/FA, CA, and correlation
      analysis suggest that Cu, Ni, and Zn are controlled by anthropogenic sources. 

PMID- 23536276
TI  - Enhanced transformation and dechlorination of p-chloronitrobenzene in the
      combined ZVI-anaerobic sludge system.
AB  - The combination of zero-valent iron (ZVI) with anaerobic sludge for enhancing
      reductive transformation and dechlorination of p-chloronitrobenzene (p-ClNB) was
      investigated in this study. p-ClNB was quickly reduced into p-chloroaniline (p
      ClAn) and subsequently dechlorinated into aniline in the complex system, and the
      strengthening factor for pseudo-first-order transformation rate constant of p
      ClNB (Q, k ZVI + sludge/(k sludge + k ZVI)) was above 3. The Q values for the
      different ZVI types with anaerobic sludge were as following: Reduced ZVI (RZVI) >
      Industrial ZVI > Nanoscale ZVI (NZVI). Thereinto, the aggregation of NZVI
      occurred, and its reaction activity declined. Furthermore, the increase of ZVI
      dosage promoted the p-ClNB transformation, but the p-ClAn dechlorination rate and
      Q value were not improved. With the anaerobic biomass increasing, the
      dechlorination rate of p-ClAn was significantly enhanced, and the Q value had
      positive relation with the mass ratio of anaerobic sludge to RZVI. 

PMID- 23536277
TI  - Effects of hydroxyapatite addition on heavy metal volatility during tannery
      sludge incineration.
AB  - The effectiveness of hydroxyapatite (HAP) on volatilization reducing of heavy
      metals during incineration of tannery sludge was investigated. The tannery sludge
      was treated through doped with different content of HAP, and then incinerated in
      the tube furnace at the temperature of 600  degrees C and 900  degrees C. The
      results showed that the volatilization rates decreased by 10.19% for Pb, 10.17%
      for Zn, 7.40% for Cu and 5.33% for Cr at 600  degrees C when the HAP content was
      raised to 20%. At 900  degrees C, the volatilization rates of Pb, Cr and Cu
      decreased by about 40.0%, 24.0% and 9.0%, respectively, while volatilization of
      Zn can be considered nearly unchanged at around 5%. The heavy metals can be
      stabilized effectively in the incineration after the pyromorphite-like minerals
      were formed in the sludge doped with HAP.

PMID- 23536278
TI  - A systematic review on micronutrient intake adequacy in adult minority
      populations residing in Europe: the need for action.
AB  - This systematic review evaluated micronutrient intake inadequacy of ten
      micronutrients for adult ethnic minority populations residing in Europe. Pubmed
      was searched for studies, related references were checked and experts consulted.
      Ten studies were identified and six were included in the final analysis
      representing Albanian, Roma, Sub-Saharan African, South Asian and African
      Caribbean minority groups. The Estimated Average Requirement cut point was
      applied to estimate inadequate intake. With the exception of a sub-Saharan
      African study, of seven micronutrients analysed, inadequate intakes were markedly
      elevated (>50 % of the population in most cases) in both genders for folate,
      vitamin B(12), calcium and iron (the latter in females only). A pressing need
      exists for intake adequacy studies with sound methodologies addressing ethnic
      minority groups in Europe. These populations constitute a vulnerable population
      for inadequate intakes and results substantiate the need for further
      investigation, interventions and policy measures to reduce their nutritional
      risk.

PMID- 23536279
TI  - High frequency of temperature-sensitive mutants of p53 in glioblastoma.
AB  - Glioblastoma is the most common and the most aggressive type of brain cancer.
      Aberrations of the RTK/RAS/PI3K-, p53-, and RB cell signaling pathways were
      recognized as a core requirement for pathogenesis of glioblastoma. The p53 tumor
      suppressor functions as a transcription factor transactivating expression of its
      target genes in response to various stress stimuli. We determined the p53 status
      in 36 samples of glioblastoma by functional analyses FASAY and split assay.
      Seventeen p53 mutations were detected and further analyzed by cDNA and gDNA
      sequencing in 17 patients (47.2 %). Fifteen (88.2 %) of the mutations were
      missense mutations causing amino acid substitutions, seven of them exhibited
      temperature-sensitivity. Two mutations were determined as short deletions, one of
      them causing formation of premature termination codon in position 247.
      Fluorescent in situ hybridization revealed the loss of the p53-specific 17p13.3
      locus in four of 33 analyzed samples (12 %). In 12 out of 30 samples (40 %), the
      p53 protein accumulation was shown by immunoblotting. There was high (80 %)
      concordance between the presence of the clonal p53 mutation and the p53 protein
      accumulation. 

PMID- 23536280
TI  - Diet induced obesity increases the risk of colonic tumorigenesis in mice.
AB  - A large body of epidemiological data indicates that obesity increases the risk of
      colon cancer in humans. There are limited studies using rodent models where the
      relationship between obesity and colon cancer has been studied. In this study,
      wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to
      investigate the influence of obesity on the risk of colon cancer. We hypothesized
      that the obese phenotype would exhibit increased colonic tumorigenesis. Colon
      cancer was chemically induced by injecting the mice with azoxymethane (AOM) at
      levels that we experimentally determined to result in equivalent AOM
      concentrations in circulating blood. Risk of colon cancer was assessed via
      microscopic examination of entire colons for aberrant crypts, aberrant crypt foci
      and proliferation levels. The DIO mice were found to have significantly more
      aberrant crypts and aberrant crypt foci as well as increased proliferation of
      colonocytes per mouse compared to wild-type control mice, supporting the
      epidemiological data that obesity increases the risk of colonic tumorigenesis. 

PMID- 23536281
TI  - In the non-cirrhotic stage of nonalcoholic steatohepatitis, angioarchitecture of
      portal veins and lobular architecture are maintained.
AB  - The morphogenesis of lobular restructuring to liver cirrhosis in nonalcoholic
      steatohepatitis (NASH) is yet to be clearly understood. Therefore, we observed
      tissue samples from three biopsies and one autopsy with NASH in the non-cirrhotic
      stage three-dimensionally to elucidate the evolution of fibrosis and the changes
      of angioarchitecture. Histologic reconstructions revealed that pericellular
      fibrosis developed around the central vein in the early stage and gradually
      progressed to arch-shaped band-like fibrosis connecting the central veins in the
      neighboring lobules. In contrast, the basic angioarchitecture of the portal vein
      in the portal tracts tended to be preserved in the non-cirrhotic stage, although
      the portal vein architecture was slightly altered as the portal tract underwent
      gradual fibrous expansion. In addition, a striking development of arteries
      originating from the portal tract was found in the fibrotic area around the
      central and sublobular veins. In summary, while central-central bridging fibrosis
      and ectopic arterial development were conspicuous, the lobular architecture was
      maintained relatively well in the non-cirrhotic stage of NASH because of only
      mildly damaged angioarchitecture of the portal veins. The process of lobular
      restructuring in NASH is considered to be different from that in chronic viral
      hepatitis in the non-cirrhotic stage.

PMID- 23536282
TI  - Platelet-derived growth factor-A and vascular endothelial growth factor-C
      contribute to the development of pulmonary tumor thrombotic microangiopathy in
      gastric cancer.
AB  - Pulmonary tumor thrombotic microangiopathy is a rare but lethal complication in
      cancer-bearing patients, particularly those with gastric cancer. It is
      characterized by cancer cell emboli with marked intimal proliferation. In the
      present study, we tried to elucidate the pathogenesis of pulmonary tumor
      thrombotic microangiopathy, notably angiogenic factors specific for cancer cells
      lodged in pulmonary arteries. An autopsy series of gastric cancer (51 cases) was
      reviewed for pulmonary tumor thrombotic microangiopathy and pulmonary tumor cell
      emboli without intimal proliferation. Pathological and immunohistochemical
      characteristics were compared between two groups. In eight cases in muscular
      pulmonary arteries, tumor thrombotic microangiopathy was noted, and in three
      cases pulmonary tumor emboli without intimal proliferation was noted.
      Histological features of pulmonary tumor thrombotic microangiopathy included
      small nests or single cancer cells accompanied by intimal proliferation, whereas
      in pulmonary tumor emboli large cell nests prevailed. By immunohistochemistry, in
      pulmonary tumor thrombotic microangiopathy, cancer cells expressed platelet
      derived growth factor-A (7/8 cases) and vascular endothelial growth factor-C
      (8/8) more frequently than in pulmonary tumor emboli (0/3 and 1/3; P = 0.02 and P
      = 0.055, respectively). Expression of tissue factor, vascular endothelial growth
      factor-A and -D, osteopontin, fibroblast growth factor-2, and platelet-derived
      growth factor-B was similar in both groups. Platelet-derived growth factor-A and
      vascular endothelial growth factor-C might induce intimal proliferation in
      pulmonary arteries and contribute to the development of pulmonary tumor
      thrombotic microangiopathy.

PMID- 23536283
TI  - Sex disparities in risk and risk factors for ischemic heart disease in the Asia
      Pacific region.
AB  - BACKGROUND: Ischemic heart disease (IHD) is the leading cause of death and
      disability worldwide, with higher rates among men than women. Relatively few
      studies on risk factor associations are available from the Asia-Pacific region,
      especially with regard to sex differences. Our objective was to compare the
      relationships between modifiable risk factors and IHD in men and women from the
      Asia-Pacific region. METHODS: Data from 600,445 individuals from 44 studies from
      the Asia Pacific Cohort Studies Collaboration, an individual patient data
      overview, were used. Cox models were used to evaluate the effects of risk factors
      on fatal and non-fatal IHD separately in men and women from Australia and New
      Zealand (ANZ) and Asia. RESULTS: Over a median follow-up of 6.7 years, 5695 IHD
      events were documented. The hazard ratio for IHD, comparing men with women, was
      2.14 (95% CI 1.97-2.33) in ANZ and 1.88 (95% CI 1.54-2.29) in Asia. The age
      adjusted prevalence of major risk factors was generally higher in men than women,
      especially in ANZ. Risk factors acted broadly similarly between men and women in
      both Asia and ANZ, with any indications of differences tending to favor men,
      rather than women. CONCLUSION: The excess risk of IHD observed in men compared
      with women in both Asia and ANZ may be, at least in part, a result of a more
      hazardous risk profile in men compared with women. The contribution of sex
      differences in the magnitude of the risk factor-disease associations is unlikely
      to be a contributing factor.

PMID- 23536284
TI  - Bone mineral density and vitamin D levels in erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is a rare disease with painful cutaneous
      photosensitivity, in which patients are recommended to avoid sun exposure, and
      wear sunscreen and adequate clothing. Our aim was to study bone mineral density
      (BMD) and other mineral parameters, including serum 25(OH)D levels, to evaluate
      the impact of these measures in the follow-up of EPP patients. A cross-sectional
      study of ten EPP patients (median age 25; range 22-55, four males and six
      females), was performed evaluating clinical features, biochemical values (bone
      markers and serum 25 hydroxyvitamin D), and BMD. Median serum 25(OH)D level was
      19.65 ng/ml [17.50; 24.80]. Four patients had 25(OH)D in insufficiency range (20
      30 ng/ml) and five patients in the deficiency range (<20 ng/ml). Lumbar T-score
      median levels were in the osteopenia range in both females (-1.50 [-2.30; -1.0])
      and males (-1.90 [-2.40; -0.70]). Also, in the female group median femoral neck T
      score were in the osteopenia range (-1.20 [-1.60; -0.60]). This is the first
      study reporting low BMD in EPP patients. Osteoporosis, osteopenia, and vitamin D
      deficiency are frequent findings in EPP patients. The contribution of sunlight
      avoidance measures to these results remains to be clarified. Serum levels of
      protoporphyrins were not related to these alterations and other factors should be
      investigated. We suggest that the monitoring of serum vitamin D levels in EPP
      patients should be mandatory, as well as vitamin D and calcium supplementation.

PMID- 23536285
TI  - Should patients with remnants from thyroid microcarcinoma really not be treated
      with iodine-131 ablation?
AB  - Remnant ablation by radioiodine is generally not recommended in patients
      presenting uni- or multifocal cancer <1 cm, in the absence of other higher risk
      features. We retrospectively studied low-risk patients (pts) with differentiated
      thyroid cancer (DTC) less than 1 cm recruited for radioiodine therapy (RAI).
      METHODS: 91 pts (79 women, age 48.4 +/- 12 yrs) with DTC were enrolled for RAI.
      Patients underwent pre-therapy ultrasonography (US), those with
      suspected/ambiguous lymph-nodes were excluded and proposed for cytology. Treated
      pts underwent post-therapeutic whole body scan (WBSt) completed by neck/chest
      SPECT/CT, when necessary (e.g. evidence of uptake outside of thyroid bed). A
      target lesion on SPECT/CT was defined as an identifiable lymph-nodal site
      presenting a matched significant iodine uptake. The patients were followed up for
      14 +/- 2 months thereafter. RESULTS: All pts/cancers were pT1. The mean
      histological diameter was 0.68 +/- 0.23 cm. Six patients were excluded because of
      suspected nodal involvement at US. Thirty (35 %) out of 85 pts had suspicious
      WBSt as per lymph-nodal involvement which was confirmed at the subsequent
      SPECT/CT acquisition in most part of pts (26/30; 86 %). Overall detected target
      lesions was 34, and nine (26 %) had interim positive fine needle cytology.
      CONCLUSIONS: a significant part of low risk DTC patients, for whom RAI is not
      recommended, presents an incidental suspicion of lymph-nodal involvement at WBSt
      confirmed by subsequent SPECT/CT. Such setting would have not been treated by I
      131.

PMID- 23536286
TI  - A new route for the prebiotic synthesis of nucleobases and hydantoins in
      water/ice solutions involving the photochemistry of acetylene.
AB  - The origin of nucleobases and other heterocycles is a classic question in the
      chemistry of the origins of life. The construction of laboratory models for the
      abiotic synthesis of nitrogen heterocycles in plausible natural conditions also
      aids the understanding and prediction of chemical species in the Solar System.
      Here, we report a new explanation for the origin of hydantoins, purines, and
      pyrimidines in eutectic water/ice/urea solutions driven by ultraviolet
      irradiation (in the 185-254 nm range, UVC) of acetylene under anoxic conditions.
      An analysis of the products indicates the synthesis of hydantoin and 5
      hydroxyhydantoin, the purines uric acid, xanthine, and guanine, and the
      pyrimidines uracil and cytosine. The synthesis occurred together with the photo
      oxidation of bases in a complex process for which possible pathways are proposed.
      In conclusion, an acetylene-containing atmosphere could contribute to the origin
      of nucleobases in the presence of a urea/water system by an HCN-independent
      mechanism. The presence of ice has a dual role as a favorable medium for the
      synthesis of nucleobases and protection against degradation and as a source of
      free radicals for the synthesis of highly oxidized heterocycles. A mechanism for
      the origin of hydantoins and uracil from urea in plausible conditions for
      prebiotic chemistry is also proposed.

PMID- 23536289
TI  - An initial and rapid step of lytic granule secretion precedes microtubule
      organizing center polarization at the cytotoxic T lymphocyte/target cell synapse.
AB  - It is presently assumed that lethal hit delivery by cytotoxic T lymphocytes
      (CTLs) is mechanistically linked to centrosome polarization toward target cells,
      leading to dedicated release of lytic granules within a confined secretory
      domain. Here we provide three lines of evidence showing that this mechanism might
      not apply as a general paradigm for lethal hit delivery. First, in CTLs
      stimulated with immobilized peptide-MHC complexes, lytic granules and microtubule
      organizing center localization into synaptic areas are spatio-temporally
      dissociated, as detected by total internal reflection fluorescence microscopy.
      Second, in many CTL/target cell conjugates, lytic granule secretion precedes
      microtubule polarization and can be detected during the first minute after cell
      cell contact. Third, inhibition of microtubule organizing center and centrosome
      polarization impairs neither lytic granule release at the CTL synapse nor killing
      efficiency. Our results broaden current views of CTL biology by revealing an
      extremely rapid step of lytic granule secretion and by showing that microtubule
      organizing center polarization is dispensable for efficient lethal hit delivery.

PMID- 23536288
TI  - Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation
      sequencing and phylogenetic pairing of heavy/light chains.
AB  - Next-generation sequencing of antibody transcripts from HIV-1-infected
      individuals with broadly neutralizing antibodies could provide an efficient means
      for identifying somatic variants and characterizing their lineages. Here, we used
      454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and
      light-chain sequences from donor N152, the source of the broadly neutralizing
      antibody 10E8. We identified variants with up to 28% difference in amino acid
      sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants
      displayed similar architectures, and 10E8 variants reconstituted from matched and
      unmatched phylogenetic branches displayed significantly lower autoreactivity when
      matched. To test the generality of phylogenetic pairing, we analyzed donor
      International AIDS Vaccine Initiative 84, the source of antibodies PGT141-145.
      Heavy- and light-chain phylogenetic trees of PGT141-145 somatic variants also
      displayed remarkably similar architectures; in this case, branch pairings could
      be anchored by known PGT141-145 antibodies. Altogether, our findings suggest that
      phylogenetic matching of heavy and light chains can provide a means to
      approximate natural pairings.

PMID- 23536287
TI  - Intrinsic connectivity network disruption in progressive supranuclear palsy.
AB  - OBJECTIVE: Progressive supranuclear palsy (PSP) has been conceptualized as a
      large-scale network disruption, but the specific network targeted has not been
      fully characterized. We sought to delineate the affected network in patients with
      clinical PSP. METHODS: Using task-free functional magnetic resonance imaging, we
      mapped intrinsic connectivity to the dorsal midbrain tegmentum (dMT), a region
      that shows focal atrophy in PSP. Two healthy control groups (1 young, 1 older)
      were used to define and replicate the normal connectivity pattern, and patients
      with PSP were compared to an independent matched healthy control group on
      measures of network connectivity. RESULTS: Healthy young and older subjects
      showed a convergent pattern of connectivity to the dMT, including brainstem,
      cerebellar, diencephalic, basal ganglia, and cortical regions involved in
      skeletomotor, oculomotor, and executive control. Patients with PSP showed
      significant connectivity disruptions within this network, particularly within
      corticosubcortical and cortico-brainstem interactions. Patients with more severe
      functional impairment showed lower mean dMT network connectivity scores.
      INTERPRETATION: This study defines a PSP-related intrinsic connectivity network
      in the healthy brain and demonstrates the sensitivity of network-based imaging
      methods to PSP-related physiological and clinical changes.

PMID- 23536290
TI  - Structure of the rare archaeal biosphere and seasonal dynamics of active ecotypes
      in surface coastal waters.
AB  - Marine Archaea are important players among microbial plankton and significantly
      contribute to biogeochemical cycles, but details regarding their community
      structure and long-term seasonal activity and dynamics remain largely unexplored.
      In this study, we monitored the interannual archaeal community composition of
      abundant and rare biospheres in northwestern Mediterranean Sea surface waters by
      pyrosequencing 16S rDNA and rRNA. A detailed analysis of the rare biosphere
      structure showed that the rare archaeal community was composed of three distinct
      fractions. One contained the rare Archaea that became abundant at different times
      within the same ecosystem; these cells were typically not dormant, and we
      hypothesize that they represent a local seed bank that is specific and essential
      for ecosystem functioning through cycling seasonal environmental conditions. The
      second fraction contained cells that were uncommon in public databases and not
      active, consisting of aliens to the studied ecosystem and representing a nonlocal
      seed bank of potential colonizers. The third fraction contained Archaea that were
      always rare but actively growing; their affiliation and seasonal dynamics were
      similar to the abundant microbes and could not be considered a seed bank. We also
      showed that the major archaeal groups, Thaumarchaeota marine group I and
      Euryarchaeota group II.B in winter and Euryarchaeota group II.A in summer,
      contained different ecotypes with varying activities. Our findings suggest that
      archaeal diversity could be associated with distinct metabolisms or life
      strategies, and that the rare archaeal biosphere is composed of a complex
      assortment of organisms with distinct histories that affect their potential for
      growth.

PMID- 23536292
TI  - Ramanujan's mock theta functions.
AB  - In his famous deathbed letter, Ramanujan introduced the notion of a mock theta
      function, and he offered some alleged examples. Recent work by Zwegers [Zwegers S
      (2001) Contemp Math 291:268-277 and Zwegers S (2002) PhD thesis (Univ of Utrecht,
      Utrecht, The Netherlands)] has elucidated the theory encompassing these examples.
      They are holomorphic parts of special harmonic weak Maass forms. Despite this
      understanding, little attention has been given to Ramanujan's original
      definition. Here, we prove that Ramanujan's examples do indeed satisfy his
      original definition.

PMID- 23536291
TI  - Spectroscopic evidence for Fermi liquid-like energy and temperature dependence of
      the relaxation rate in the pseudogap phase of the cuprates.
AB  - Cuprate high-Tc superconductors exhibit enigmatic behavior in the
      nonsuperconducting state. For carrier concentrations near "optimal doping" (with
      respect to the highest Tcs) the transport and spectroscopic properties are unlike
      those of a Landau-Fermi liquid. On the Mott-insulating side of the optimal
      carrier concentration, which corresponds to underdoping, a pseudogap removes
      quasi-particle spectral weight from parts of the Fermi surface and causes a
      breakup of the Fermi surface into disconnected nodal and antinodal sectors. Here,
      we show that the near-nodal excitations of underdoped cuprates obey Fermi liquid
      behavior. The lifetime tau(omega, T) of a quasi-particle depends on its energy
      omega as well as on the temperature T. For a Fermi liquid, 1/tau(omega, T) is
      expected to collapse on a universal function proportional to (homega)(2) +
      (ppik(B)T)(2). Magneto-transport experiments, which probe the properties in the
      limit omega = 0, have provided indications for the presence of a T(2) dependence
      of the dc (omega = 0) resistivity of different cuprate materials. However, Fermi
      liquid behavior is very much about the energy dependence of the lifetime, and
      this can only be addressed by spectroscopic techniques. Our optical experiments
      confirm the aforementioned universal omega- and T dependence of 1/tau(omega, T),
      with p ~ 1.5. Our data thus provide a piece of evidence in favor of a Fermi
      liquid-like scenario of the pseudogap phase of the cuprates.

PMID- 23536293
TI  - Biased assimilation, homophily, and the dynamics of polarization.
AB  - We study the issue of polarization in society through a model of opinion
      formation. We say an opinion formation process is polarizing if it results in
      increased divergence of opinions. Empirical studies have shown that homophily,
      i.e., greater interaction between like-minded individuals, results in
      polarization. However, we show that DeGroot's well-known model of opinion
      formation based on repeated averaging can never be polarizing, even if
      individuals are arbitrarily homophilous. We generalize DeGroot's model to account
      for a phenomenon well known in social psychology as biased assimilation: When
      presented with mixed or inconclusive evidence on a complex issue, individuals
      draw undue support for their initial position, thereby arriving at a more extreme
      opinion. We show that in a simple model of homophilous networks, our biased
      opinion formation process results in polarization if individuals are sufficiently
      biased. In other words, homophily alone, without biased assimilation, is not
      sufficient to polarize society. Quite interestingly, biased assimilation also
      provides a framework to analyze the polarizing effect of Internet-based
      recommender systems that show us personalized content.

PMID- 23536294
TI  - Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil
      trafficking in vivo.
AB  - Most in vivo studies of granulocytes draw conclusions about their trafficking
      based on examination of their steady-state tissue/blood levels, which result from
      a combination of tissue homing, survival, and egress, rather than direct
      examination of cellular trafficking. Herein, we developed a unique cell transfer
      system involving the adoptive transfer of a genetically labeled, bone-marrow
      derived unique granulocyte population (eosinophils) into an elicited inflammatory
      site, the allergic lung. A dual polychromatic FACS-based biomarker-labeling
      system based on the IL4-eGFP transgene (4get) or Cd45.1 allele was used to track
      i.v. transferred eosinophils into the airway following allergen or T(H)2
      associated stimuli in the lung in multiple mouse strains. The system was amenable
      to reverse tagging of recipients, thus allowing transfer of nonlabeled
      eosinophils and competitive tracking of multiple populations of eosinophils in
      vivo. The half-life of eosinophils in the blood was 3 h, and migration to the
      lung was dependent upon the dosage of transferred eosinophils, sensitive to
      pertussis toxin pretreatment, peaked at ~24 h after adoptive transfer, and
      revealed a greater than 8-d eosinophil half-life in the lung. Eosinophil
      migration to the lung was dependent upon recipient IL-5 and IL-13 receptor alpha1
      and donor eosinophil C-C chemokine receptor type 3 (CCR3) and interleukin 1
      receptor-like 1 (ST2) in vivo. Taken together, this unique eosinophil transfer
      system provides an unprecedented opportunity to examine airway eosinophil
      migration without the need for extensive efforts to acquire donor source and time
      consuming genetic crossing and has already been used to identify a long
      eosinophil half-life in the allergic lung and a definite role for ST2 in
      regulating eosinophil trafficking.

PMID- 23536295
TI  - Toward an atomistic description of the urea-denatured state of proteins.
AB  - We present here the characterization of the structural, dynamics, and energetics
      of properties of the urea-denatured state of ubiquitin, a small prototypical
      soluble protein. By combining state-of-the-art molecular dynamics simulations
      with NMR and small-angle X-ray scattering data, we were able to: (i) define the
      unfolded state ensemble, (ii) understand the energetics stabilizing unfolded
      structures in urea, (iii) describe the dedifferential nature of the interactions
      of the fully unfolded proteins with urea and water, and (iv) characterize the
      early stages of protein refolding when chemically denatured proteins are
      transferred to native conditions. The results presented herein are unique in
      providing a complete picture of the chemically unfolded state of proteins and
      contribute to deciphering the mechanisms that stabilize the native state of
      proteins, as well as those that maintain them unfolded in the presence of urea.

PMID- 23536296
TI  - Single-cell label-free photoacoustic flowoxigraphy in vivo.
AB  - Label-free functional imaging of single red blood cells (RBCs) in vivo holds the
      key to uncovering the fundamental mechanism of oxygen metabolism in cells. To
      this end, we developed single-RBC photoacoustic flowoxigraphy (FOG), which can
      image oxygen delivery from single flowing RBCs in vivo with millisecond-scale
      temporal resolution and micrometer-scale spatial resolution. Using intrinsic
      optical absorption contrast from oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR),
      FOG allows label-free imaging. Multiple single-RBC functional parameters,
      including total hemoglobin concentration (C(Hb)), oxygen saturation (sO2), sO2
      gradient (VsO2), flow speed (v(f)), and oxygen release rate (rO2), have been
      quantified simultaneously in real time. Working in reflection instead of
      transmission mode, the system allows minimally invasive imaging at more
      anatomical sites. We showed the capability to measure relationships among sO2,
      VsO2, v(f), and rO2 in a living mouse brain. We also demonstrated that single-RBC
      oxygen delivery was modulated by changing either the inhalation gas or blood
      glucose. Furthermore, we showed that the coupling between neural activity and
      oxygen delivery could be imaged at the single-RBC level in the brain. The single
      RBC functional imaging capability of FOG enables numerous biomedical studies and
      clinical applications.

PMID- 23536298
TI  - Integrated transcriptional and competitive endogenous RNA networks are cross
      regulated in permissive molecular environments.
AB  - Competitive endogenous (ce)RNAs cross-regulate each other through sequestration
      of shared microRNAs and form complex regulatory networks based on their microRNA
      signature. However, the molecular requirements for ceRNA cross-regulation and the
      extent of ceRNA networks remain unknown. Here, we present a mathematical mass
      action model to determine the optimal conditions for ceRNA activity in silico.
      This model was validated using phosphatase and tensin homolog (PTEN) and its
      ceRNA VAMP (vesicle-associated membrane protein)-associated protein A (VAPA) as
      paradigmatic examples. A computational assessment of the complexity of ceRNA
      networks revealed that transcription factor and ceRNA networks are intimately
      intertwined. Notably, we found that ceRNA networks are responsive to
      transcription factor up-regulation or their aberrant expression in cancer. Thus,
      given optimal molecular conditions, alterations of one ceRNA can have striking
      effects on integrated ceRNA and transcriptional networks.

PMID- 23536297
TI  - Responses of Mn2+ speciation in Deinococcus radiodurans and Escherichia coli to
      gamma-radiation by advanced paramagnetic resonance methods.
AB  - The remarkable ability of bacterium Deinococcus radiodurans to survive extreme
      doses of gamma-rays (12,000 Gy), 20 times greater than Escherichia coli, is
      undiminished by loss of Mn-dependent superoxide dismutase (SodA). D. radiodurans
      radiation resistance is attributed to the accumulation of low-molecular-weight
      (LMW) "antioxidant" Mn(2+)-metabolite complexes that protect essential enzymes
      from oxidative damage. However, in vivo information about such complexes within
      D. radiodurans cells is lacking, and the idea that they can supplant reactive
      oxygen-species (ROS)-scavenging enzymes remains controversial. In this report,
      measurements by advanced paramagnetic resonance techniques [electron-spin-echo
      (ESE)-EPR/electron nuclear double resonance/ESE envelope modulation (ESEEM)]
      reveal differential details of the in vivo Mn(2+) speciation in D. radiodurans
      and E. coli cells and their responses to 10 kGy gamma-irradiation. The Mn(2+) of
      D. radiodurans exists predominantly as LMW complexes with nitrogenous metabolites
      and orthophosphate, with negligible EPR signal from Mn(2+) of SodA. Thus, the
      extreme radiation resistance of D. radiodurans cells cannot be attributed to
      SodA. Correspondingly, 10 kGy irradiation causes no change in D. radiodurans
      Mn(2+) speciation, despite the paucity of holo-SodA. In contrast, the EPR signal
      of E. coli is dominated by signals from low-symmetry enzyme sites such as that of
      SodA, with a minority pool of LMW Mn(2+) complexes that show negligible
      coordination by nitrogenous metabolites. Nonetheless, irradiation of E. coli
      majorly changes LMW Mn(2+) speciation, with extensive binding of nitrogenous
      ligands created by irradiation. We infer that E. coli is highly susceptible to
      radiation-induced ROS because it lacks an adequate supply of LMW Mn antioxidants.

PMID- 23536299
TI  - Predicting climate effects on Pacific sardine.
AB  - For many marine species and habitats, climate change and overfishing present a
      double threat. To manage marine resources effectively, it is necessary to adapt
      management to changes in the physical environment. Simple relationships between
      environmental conditions and fish abundance have long been used in both fisheries
      and fishery management. In many cases, however, physical, biological, and human
      variables feed back on each other. For these systems, associations between
      variables can change as the system evolves in time. This can obscure
      relationships between population dynamics and environmental variability,
      undermining our ability to forecast changes in populations tied to physical
      processes. Here we present a methodology for identifying physical forcing
      variables based on nonlinear forecasting and show how the method provides a
      predictive understanding of the influence of physical forcing on Pacific sardine.

PMID- 23536300
TI  - A predictive, size-dependent continuum model for dense granular flows.
AB  - Dense granular materials display a complicated set of flow properties, which
      differentiate them from ordinary fluids. Despite their ubiquity, no model has
      been developed that captures or predicts the complexities of granular flow,
      posing an obstacle in industrial and geophysical applications. Here we propose a
      3D constitutive model for well-developed, dense granular flows aimed at filling
      this need. The key ingredient of the theory is a grain-size-dependent nonlocal
      rheology--inspired by efforts for emulsions--in which flow at a point is affected
      by the local stress as well as the flow in neighboring material. The microscopic
      physical basis for this approach borrows from recent principles in soft glassy
      rheology. The size-dependence is captured using a single material parameter, and
      the resulting model is able to quantitatively describe dense granular flows in an
      array of different geometries. Of particular importance, it passes the stringent
      test of capturing all aspects of the highly nontrivial flows observed in split
      bottom cells--a geometry that has resisted modeling efforts for nearly a decade.
      A key benefit of the model is its simple-to-implement and highly predictive final
      form, as needed for many real-world applications.

PMID- 23536302
TI  - A phase transition in the first passage of a Brownian process through a
      fluctuating boundary with implications for neural coding.
AB  - Finding the first time a fluctuating quantity reaches a given boundary is a
      deceptively simple-looking problem of vast practical importance in physics,
      biology, chemistry, neuroscience, economics, and industrial engineering. Problems
      in which the bound to be traversed is itself a fluctuating function of time
      include widely studied problems in neural coding, such as neuronal integrators
      with irregular inputs and internal noise. We show that the probability p(t) that
      a Gauss-Markov process will first exceed the boundary at time t suffers a phase
      transition as a function of the roughness of the boundary, as measured by its
      Holder exponent H. The critical value occurs when the roughness of the boundary
      equals the roughness of the process, so for diffusive processes the critical
      value is Hc = 1/2. For smoother boundaries, H > 1/2, the probability density is a
      continuous function of time. For rougher boundaries, H < 1/2, the probability is
      concentrated on a Cantor-like set of zero measure: the probability density
      becomes divergent, almost everywhere either zero or infinity. The critical point
      Hc = 1/2 corresponds to a widely studied case in the theory of neural coding, in
      which the external input integrated by a model neuron is a white-noise process,
      as in the case of uncorrelated but precisely balanced excitatory and inhibitory
      inputs. We argue that this transition corresponds to a sharp boundary between
      rate codes, in which the neural firing probability varies smoothly, and temporal
      codes, in which the neuron fires at sharply defined times regardless of the
      intensity of internal noise.

PMID- 23536301
TI  - Fly cryptochrome and the visual system.
AB  - Cryptochromes are flavoproteins, structurally and evolutionarily related to
      photolyases, that are involved in the development, magnetoreception, and temporal
      organization of a variety of organisms. Drosophila CRYPTOCHROME (dCRY) is
      involved in light synchronization of the master circadian clock, and its C
      terminus plays an important role in modulating light sensitivity and activity of
      the protein. The activation of dCRY by light requires a conformational change,
      but it has been suggested that activation could be mediated also by specific
      "regulators" that bind the C terminus of the protein. This C-terminal region
      harbors several protein-protein interaction motifs, likely relevant for signal
      transduction regulation. Here, we show that some functional linear motifs are
      evolutionarily conserved in the C terminus of cryptochromes and that class III
      PDZ-binding sites are selectively maintained in animals. A coimmunoprecipitation
      assay followed by mass spectrometry analysis revealed that dCRY interacts with
      Retinal Degeneration A (RDGA) and with Neither Inactivation Nor Afterpotential C
      (NINAC) proteins. Both proteins belong to a multiprotein complex (the Signalplex)
      that includes visual-signaling molecules. Using bioinformatic and molecular
      approaches, dCRY was found to interact with Neither Inactivation Nor
      Afterpotential C through Inactivation No Afterpotential D (INAD) in a light
      dependent manner and that the CRY-Inactivation No Afterpotential D interaction is
      mediated by specific domains of the two proteins and involves the CRY C terminus.
      Moreover, an impairment of the visual behavior was observed in fly mutants for
      dCRY, indicative of a role, direct or indirect, for this photoreceptor in fly
      vision.

PMID- 23536303
TI  - Neuroprediction of future rearrest.
AB  - Identification of factors that predict recurrent antisocial behavior is integral
      to the social sciences, criminal justice procedures, and the effective treatment
      of high-risk individuals. Here we show that error-related brain activity elicited
      during performance of an inhibitory task prospectively predicted subsequent
      rearrest among adult offenders within 4 y of release (N = 96). The odds that an
      offender with relatively low anterior cingulate activity would be rearrested were
      approximately double that of an offender with high activity in this region,
      holding constant other observed risk factors. These results suggest a potential
      neurocognitive biomarker for persistent antisocial behavior.

PMID- 23536304
TI  - Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following
      selective delivery of boron by rationally designed liposomes.
AB  - The application of boron neutron capture therapy (BNCT) following liposomal
      delivery of a (10)B-enriched polyhedral borane and a carborane against mouse
      mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with
      a mean diameter of 134 nm or less, composed of an equimolar mixture of
      cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating
      Na3[1-(2'-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8
      C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice
      bearing right flank EMT6 tumors. Biodistribution studies indicated that two
      identical injections given 24 h apart resulted in tumor boron levels exceeding 67
      ug/g tumor at 54 h--with tumor/blood boron ratios being greatest at 96 h (5.68:1;
      43 ug boron/g tumor)--following the initial injection. For BNCT experiments,
      tumor-bearing mice were irradiated 54 h after the initial injection for 30 min
      with thermal neutrons, resulting in a total fluence of 1.6 * 10(12) neutrons per
      cm(2) (+/-7%). Significant suppression of tumor growth was observed in mice given
      BNCT vs. control mice (only 424% increase in tumor volume at 14 d post
      irradiation vs. 1551% in untreated controls). In a separate experiment in which
      mice were given a second injection/irradiation treatment 7 d after the first, the
      tumor growth was vastly diminished (186% tumor volume increase at 14 d). A
      similar response was obtained for mice irradiated for 60 min (169% increase at 14
      d), suggesting that neutron fluence was the limiting factor controlling BNCT
      efficacy in this study.

PMID- 23536306
TI  - Production is a poor metric for identifying regime-like behavior in marine
      stocks.

PMID- 23536305
TI  - Genomic and functional characterizations of phosphodiesterase subtype 4D in human
      cancers.
AB  - Discovery of cancer genes through interrogation of genomic dosage is one of the
      major approaches in cancer research. In this study, we report that
      phosphodiesterase subtype 4D (PDE4D) gene was homozygously deleted in 198 cases
      of 5,569 primary solid tumors (3.56%), with most being internal microdeletions.
      Unexpectedly, the microdeletions did not result in loss of their gene products.
      Screening PDE4D expression in 11 different types of primary tumor samples (n =
      165) with immunohistochemistry staining revealed that its protein levels were up
      regulated compared with corresponding nontransformed tissues. Importantly,
      depletion of endogenous PDE4D with three independent shRNAs caused apoptosis and
      growth inhibition in multiple types of cancer cells, including breast, lung,
      ovary, endometrium, gastric, and melanoma, which could be rescued by reexpression
      of PDE4D. We further showed that antitumor events triggered by PDE4D suppression
      were lineage-dependently associated with Bcl-2 interacting mediator of cell death
      (BIM) induction and microphthalmia-associated transcription factor (MITF) down
      regulation. Furthermore, ectopic expression of the PDE4D short isoform, PDE4D2,
      enhanced the proliferation of cancer cells both in vitro and in vivo. Moreover,
      treatment of cancer cells with a unique specific PDE4D inhibitor, 26B, triggered
      massive cell death and growth retardation. Notably, these antineoplastic effects
      induced by either shRNAs or small molecule occurred preferentially in cancer
      cells but not in nonmalignant epithelial cells. These results suggest that
      although targeted by genomic homozygous microdeletions, PDE4D functions as a
      tumor-promoting factor and represents a unique targetable enzyme of cancer cells.

PMID- 23536307
TI  - Shear stress regulates endothelial microparticle release.
AB  - RATIONALE: Endothelial activation and apoptosis release membrane-shed
      microparticles (EMP) that emerge as important biological effectors. OBJECTIVE:
      Because laminar shear stress (SS) is a major physiological regulator of
      endothelial survival, we tested the hypothesis that SS regulates EMP release.
      METHODS AND RESULTS: EMP levels were quantified by flow cytometry in medium of
      endothelial cells subjected to low or high SS (2 and 20 dyne/cm(2)). EMP levels
      augmented with time in low SS conditions compared with high SS conditions. This
      effect was sensitive to extracellular signal-regulated protein kinases 1 and 2
      (ERK1/2) and Rho kinases inhibitors but unaffected by caspase inhibitors. Low SS
      stimulated EMP release was associated with increased endothelial Rho kinases and
      ERK1/2 activities and cytoskeletal reorganization. Overexpression of
      constitutively active RhoA stimulated EMP release under high SS. We also examined
      the effect of nitric oxide (NO) in mediating SS effects. L-NG-nitroarginine
      methyl ester (L-NAME), but not D-NG-nitroarginine methyl ester, increased high SS
      induced EMP levels by 3-fold, whereas the NO donor S-nitroso-N-acetyl-D,L
      penicillamine (SNAP) decreased it. L-NAME and SNAP did not affect Rho kinases and
      ERK1/2 activities. Then, we investigated NO effect on membrane remodeling because
      microparticle release is abolished in ABCA1-deficient cells. ABCA1 expression,
      which was greater under low SS than under high SS, was augmented by L-NAME under
      high SS and decreased by SNAP under low SS conditions. CONCLUSIONS: Altogether,
      these results demonstrate that sustained atheroprone low SS stimulates EMP
      release through activation of Rho kinases and ERK1/2 pathways, whereas
      atheroprotective high SS limits EMP release in a NO-dependent regulation of ABCA1
      expression and of cytoskeletal reorganization. These findings, therefore,
      identify endothelial SS as a physiological regulator of microparticle release.

PMID- 23536308
TI  - RNA interference targeting CD147 inhibits the invasion of human cervical squamous
      carcinoma cells by downregulating MMP-9.
AB  - Cervical squamous carcinoma is a highly invasive tumour that has a great capacity
      to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or
      CD147), a member of the immunoglobulin superfamily, is a widely distributed cell
      surface glycoprotein. It is highly expressed on malignant tumour cell surfaces,
      including human cervical squamous carcinoma. It also plays a critical role in the
      invasive and metastatic activity of malignant cells by stimulating the expression
      of matrix metalloproteinases (MMPs). The anti-invasive effect of small
      interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells
      and its possible pathways has been investigated. The downregulation of CD147 by
      transfection with siRNA resulted in MMP-9 expression and decreased activity in
      the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the
      invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent
      MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of
      human cervical squamous carcinoma cells.

PMID- 23536309
TI  - The diagnosis and treatment of myotonic disorders.
AB  - Myotonia is a defining clinical symptom and sign common to a relatively small
      group of muscle diseases, including the myotonic dystrophies and the
      nondystrophic myotonic disorders. Myotonia can be observed on clinical
      examination, as can its electrical correlate, myotonic discharges, on
      electrodiagnostic testing. Research interest in the myotonic disorders continues
      to expand rapidly, which justifies a review of the scientific bases, clinical
      manifestations, and numerous therapeutic approaches associated with these
      disorders. We review the pathomechanisms of myotonia, the clinical features of
      the dystrophic and nondystrophic myotonic disorders, and the diagnostic approach
      and treatment options for patients with symptomatic myotonia.

PMID- 23536310
TI  - A new cytokine release assay: a simple approach to monitor the immune status of
      HIV-infected patients.
AB  - PURPOSE: To test a new assay based on an ex vivo cytokine release from whole
      blood for the monitoring of immune changes in human immunodeficiency virus (HIV)
      infected patients. METHODS: A pilot study of outpatients with HIV infection (n =
      9) at a large academic hospital who were divided into three groups: HIV-infected
      patients on highly active antiretroviral therapy (HAART) with a CD4(+) cell count
      >350/MUL (group I) or a CD4(+) cell count <350/MUL (group II) and HIV-infected
      HAART-naive subjects with a CD4(+) cell count >350/MUL (group III). All groups
      were compared with healthy volunteers (n = 3). The ex vivo cytokine release assay
      was performed in a three-step process: (1) blood collection, (2) whole-blood ex
      vivo incubation over 48 h without or with a standard set of well-defined recall
      antigens as comparable to those used formerly in the skin delayed-type
      hypersensitivity (DTH) test, (3) cytokine determination from the assay
      supernatant. RESULTS: Under stimulated conditions, untreated HIV-infected
      patients with a CD4(+) count >350/MUL had similar interleukin-2 (IL-2) levels in
      the supernatant of the whole-blood incubation to HIV-infected patients on HAART
      with a low CD4(+) count. Both groups revealed lower IL-2 levels in the
      supernatant than HIV-infected patients on HAART and with a CD4(+) count >350/MUL
      or healthy volunteers. The determination of interferon-gamma and tumour necrosis
      factor-alpha in the supernatant showed a similar arrangement of cytokines between
      groups. CONCLUSIONS: Our results suggest that this cytokine release assay could
      be a suitable tool to mirror the immunological responsiveness of patients with
      HIV infection in a gradual manner; further studies are required in order to
      assess its value in HAART monitoring.

PMID- 23536311
TI  - RNA processing and decay in plastids.
AB  - Plastids were derived through endosymbiosis from a cyanobacterial ancestor, whose
      uptake was followed by massive gene transfer to the nucleus, resulting in the
      compact size and modest coding capacity of the extant plastid genome. Plastid
      gene expression is essential for plant development, but depends on nucleus
      encoded proteins recruited from cyanobacterial or host-cell origins. The plastid
      genome is heavily transcribed from numerous promoters, giving posttranscriptional
      events a critical role in determining the quantity and sizes of accumulating RNA
      species. The major events reviewed here are RNA editing, which restores protein
      conservation or creates correct open reading frames by converting C residues to
      U, RNA splicing, which occurs both in cis and trans, and RNA cleavage, which
      relies on a variety of exoribonucleases and endoribonucleases. Because the RNases
      have little sequence specificity, they are collectively able to remove extraneous
      RNAs whose ends are not protected by RNA secondary structures or sequence
      specific RNA-binding proteins (RBPs). Other plastid RBPs, largely members of the
      helical-repeat superfamily, confer specificity to editing and splicing reactions.
      The enzymes that catalyze RNA processing are also the main actors in RNA decay,
      implying that these antagonistic roles are optimally balanced. We place the
      actions of RBPs and RNases in the context of a recent proteomic analysis that
      identifies components of the plastid nucleoid, a protein-DNA complex with
      multiple roles in gene expression. These results suggest that sublocalization
      and/or concentration gradients of plastid proteins could underpin the regulation
      of RNA maturation and degradation.

PMID- 23536312
TI  - The effect of sacral nerve stimulation on distal colonic motility in patients
      with faecal incontinence.
AB  - BACKGROUND: Sacral nerve stimulation (SNS) is an effective treatment for
      neurogenic faecal incontinence (FI). However, the clinical improvement that
      patients experience cannot be explained adequately by changes in anorectal
      function. The aim of this study was to examine the effect of SNS on colonic
      propagating sequences (PSs) in patients with FI in whom urgency and incontinence
      was the predominant symptom. METHODS: In patients with FI a high-resolution fibre
      optic manometry catheter, containing 90 sensors spaced at 1-cm intervals, was
      positioned colonoscopically and clipped to the caecum. A unipolar or quadripolar
      tined electrode was implanted into the S3 sacral nerve foramen. Colonic manometry
      was evaluated in a double-blind randomized crossover trial, using true
      suprasensory stimulation or sham stimulation. Each stimulation period, lasting 2
      h, was preceded by a 2-h basal manometric recording. RESULTS: All 11 patients
      studied showed a colonic response to SNS. In ten patients there was a significant
      increase in the frequency of retrograde PSs throughout the colon during true
      stimulation compared with sham stimulation (P = 0.014). In one outlier, with
      baseline retrograde PS frequency nine times that of the nearest patient, a
      reduction in retrograde PS frequency was recorded. Compared with sham
      stimulation, SNS had no effect on the frequency of antegrade PSs or high
      amplitude PSs. CONCLUSION: SNS modulates colonic motility in patients with faecal
      urge incontinence. These data suggest that SNS may improve continence and urgency
      through alteration of colonic motility, particularly by increasing retrograde PSs
      in the left colon.

PMID- 23536314
TI  - Neuroprotective effects of cilostazol on retinal ganglion cell damage in diabetic
      rats.
AB  - Neurodegeneration is an important component of diabetic retinopathy, with
      increasing evidence that retinal ganglion cell (RGC) death occurs early in
      diabetes. We investigated the effects of cilostazol, which has been widely used
      to manage diabetic complications, on retinal ganglion cell death in the diabetic
      retina. Four-week-old Otsuka Long-Evans Tokushima fatty (OLETF) rats and Long
      Evans Tokushima Otsuka (LETO) rats as matched nondiabetic controls were treated
      with daily oral cilostazol at 30 mg/kg or 0.9% saline solution. In OLETF rats at
      the age of 40 weeks, glial fibrillary acidic protein (GFAP) immunofluorescence
      staining was upregulated in vertical sections, and showed a more ramified pattern
      in whole-mount retinas compared with that in LETO rats. Vascular endothelial
      growth factor (VEGF) expression was limited to the ganglion cell layer in LETO
      rats, but extended into the outer plexiform layer in OLETF rats.
      Immunofluorescence staining and Western blotting demonstrated that cilostazol
      treatment reduced GFAP and VEGF expression in the retinas of OLETF rats. Terminal
      deoxynucleotidyl transferase-mediated terminal deoxynucleotidyl transferase
      mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL) staining revealed an
      increase in the RGC layer in OLETF compared with LETO rats (P < 0.05), and
      cilostazol treatment reduced the number of TUNEL-positive cells in OLETF rats (P
      < 0.05). Relieving retinal ischemia by systemic cilostazol treatment had a
      noticeable protective effect on RGCs in diabetic rats. Cilostazol treatment may
      be useful for the management of diabetic retinal vascular dysfunction and
      neuronal degeneration.

PMID- 23536313
TI  - Impaired glutamate recycling and GluN2B-mediated neuronal calcium overload in
      mice lacking TGF-beta1 in the CNS.
AB  - Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine expressed
      throughout the CNS. Previous studies demonstrated that TGF-beta1 contributes to
      maintain neuronal survival, but mechanistically this effect is not well
      understood. We generated a CNS-specific TGF-beta1-deficient mouse model to
      investigate the functional consequences of TGF-beta1-deficiency in the adult
      mouse brain. We found that depletion of TGF-beta1 in the CNS resulted in a loss
      of the astrocyte glutamate transporter (GluT) proteins GLT-1 (EAAT2) and GLAST
      (EAAT1) and decreased glutamate uptake in the mouse hippocampus. Treatment with
      TGF-beta1 induced the expression of GLAST and GLT-1 in cultured astrocytes and
      enhanced astroglial glutamate uptake. Similar to GLT-1-deficient mice, CNS-TGF
      beta1-deficient mice had reduced brain weight and neuronal loss in the CA1
      hippocampal region. CNS-TGF-beta1-deficient mice showed GluN2B-dependent aberrant
      synaptic plasticity in the CA1 area of the hippocampus similar to the glutamate
      transport inhibitor DL-TBOA and these mice were highly sensitive to excitotoxic
      injury. In addition, hippocampal neurons from TGF-beta1-deficient mice had
      elevated GluN2B-mediated calcium signals in response to extrasynaptic glutamate
      receptor stimulation, whereas cells treated with TGF-beta1 exhibited reduced
      GluN2B-mediated calcium signals. In summary, our study demonstrates a previously
      unrecognized function of TGF-beta1 in the CNS to control extracellular glutamate
      homeostasis and GluN2B-mediated calcium responses in the mouse hippocampus.

PMID- 23536315
TI  - Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs.
AB  - The formation of neutrophil extracellular traps (NETs) is a newly described
      phenomenon that increases the bacteria-killing ability and the inflammatory
      response of neutrophils. Because NET generation occurs in an inflammatory
      microenvironment, we examined its regulation by anti-inflammatory drugs.
      Treatment of neutrophils with dexamethasone had no effect, but acetylsalicylic
      acid (ASA) treatment prevented NET formation. NETosis was also abrogated by the
      presence of BAY 11-7082 [(E)-3-[4-methylphenylsulfonyl]-2-propenenitrile] and Ro
      106-9920 [6-(phenylsulfinyl)tetrazolo[1,5-b]pyridazine], two structurally
      unrelated nuclear factor-kappaB (NF-kappaB) inhibitors. The decrease in NET
      formation mediated by ASA, BAY-11-7082, and Ro 106-9920 was correlated with a
      significant reduction in the phosphorylation of NF-kappaB p65 subunit, indicating
      that the activation of this transcription factor is a relevant signaling pathway
      involved in the generation of DNA traps. The inhibitory effect of these drugs was
      also observed when NET generation was induced under acidic or hyperthermic
      conditions, two stress signals of the inflammatory microenvironment. In a mouse
      peritonitis model, while pretreatment of animals with ASA or BAY 11-7082 resulted
      in a marked suppression of NET formation along with increased bacteremia,
      dexamethasone had no effect. Our results show that NETs have an important role in
      the local control of infection and that ASA and NF-kappaB blockade could be
      useful therapies to avoid undesired effect of persistent neutrophil activation.

PMID- 23536316
TI  - Chrysin ameliorates chemically induced colitis in the mouse through modulation of
      a PXR/NF-kappaB signaling pathway.
AB  - Targeted activation of pregnane X receptor (PXR) in recent years has become a
      therapeutic strategy for inflammatory bowel disease. Chrysin is a naturally
      occurring flavonoid with anti-inflammation activity. The current study
      investigated the role of chrysin as a putative mouse PXR agonist in preventing
      experimental colitis. Pre-administration of chrysin ameliorated inflammatory
      symptoms in mouse models of colitis (dextran sodium sulfate- and 2,4,6
      trinitrobenzene sulfonic acid-induced) and resulted in down-regulation of nuclear
      transcription factor kappaB (NF-kappaB) target genes (inducible NO synthase,
      intercellular adhesion molecule-1, monocyte chemotactic protein-1, cyclooxygenase
      2, tumor necrosis factor-alpha, and interleukin 6) in the colon mucosa. Chrysin
      inhibited the phosphorylation/degradation of inhibitor kappaBalpha
      (IkappaBalpha), which correlated with the decrease in the activity of
      myeloperoxidase and the levels of tumor necrosis factor-alpha and interleukin 6
      in the colon. Consistent with the in vivo results, chrysin blocked
      lipopolysaccharide -stimulated nuclear translocation of NF-kappaB p65 in mouse
      macrophage RAW264.7. Furthermore, chrysin dose-dependently activated human/mouse
      PXR in reporter gene assays and up-regulated xenobiotic detoxification genes in
      the colon mucosa, but not in the liver. Silencing of PXR by RNA interference
      demonstrated necessity of PXR in mediating chrysin's ability to induce xenobiotic
      detoxification genes and NF-kappaB inactivation. The repression of NF-kappaB
      transcription activity by chrysin was confirmed by in vitro PXR transduction.
      These findings suggest that the effect of chrysin in preventing chemically
      induced colitis is mediated in large part by a PXR/NF-kappaB pathway. The data
      also suggest that chrysin or chrysin-like flavonoids could be further developed
      as intestine-specific PXR activators.

PMID- 23536318
TI  - Distribution of different isoforms of receptor protein tyrosine phosphatase gamma
      (Ptprg-RPTP gamma) in adult mouse brain: upregulation during neuroinflammation.
AB  - The receptor protein tyrosine phosphatase gamma (Ptprg-RPTPgamma) is a receptor
      protein widely expressed in many tissues, including the central nervous system
      (CNS). Several RPTPgamma isoforms are expressed in the brain during development
      and in adulthood, but their distribution and role are unknown. In this study, we
      investigated the distribution of some RPTPgamma isoforms in the adult brain using
      antibodies against the epitopes localized in the C- and in the N-terminal domains
      of the full length isoform of RPTPgamma. We found a predominant and widespread
      neuronal positivity throughout the neocortex, hippocampus, striatum and in many
      nuclei of the brainstem and cerebellum. At least 2 distinct isoforms that can co
      exist in various compartments in the same cell are detectable in different neuron
      types. Immunopositivity for epitopes located in both the N- and C-terminus
      domains were found in the neuropil of cortical and hippocampal neurons, whereas
      the N-terminal domain positivity was found in the soma, often without
      colocalization with its C-terminal counterpart. Among glial cells, some
      protoplasmic and perivascular astrocytes and the cerebellar Bergmann glia,
      express RPTPgamma. The astrocytic expression of RPTPgamma and putative processing
      isoforms of 120 and 80 kDa increases during neuroinflammation, in particular 24 h
      after LPS treatment. Activated astrocytes were found to be strongly positive for
      RPTPgamma also in a mice model of Alzheimer's disease. Our results confirm
      previous findings and enrich the current knowledge of RPTPgamma distribution in
      the CNS, highlighting a role of RPTPgamma during neuroinflammation processes. 

PMID- 23536317
TI  - Interactions between MU-opioid receptor agonists and cannabinoid receptor
      agonists in rhesus monkeys: antinociception, drug discrimination, and drug self
      administration.
AB  - Cannabinoid receptor agonists enhance the antinociceptive effects of MU-opioid
      receptor agonists, which suggests that combinations of these drugs might enhance
      therapeutic effectiveness (e.g., analgesia). However, it is not clear whether
      combinations of these drugs also enhance abuse or dependence liability. This
      experiment examined whether combinations of cannabinoids and opioids that enhance
      antinociception also increase abuse-related effects by studying the effects of
      the cannabinoid receptor agonists 2-[(1R,2R,5R)-5-hydroxy-2-(3
      hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol (CP 55,940) and (R)-(+)
      [2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6
      yl]-1-naphthalenylmethanone mesylate (WIN 55,212) on the antinociceptive,
      discriminative stimulus, and positive reinforcing effects of MU-opioid receptor
      agonists in rhesus monkeys. In one group of monkeys (n = 3), morphine (0.1-5.6
      mg/kg s.c.), CP 55,940 (0.0032-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg
      s.c.) dose-dependently increased tail withdrawal latency from 50 degrees C water,
      and pretreatment with small, otherwise ineffective, doses of CP 55,940 and WIN
      55,212 shifted the morphine dose-effect curve to the left. In monkeys (n = 3)
      discriminating 3.2 mg/kg morphine, CP 55,940 (0.01-0.032 mg/kg s.c.) and WIN
      55,212 (0.1-1.78 mg/kg s.c.) attenuated the discriminative stimulus effects of
      morphine, shifting the dose-effect curve to the right. In monkeys (n = 4) self
      administering heroin (0.32-32.0 ug/kg/infusion i.v.), CP 55,940 (0.001-0.032
      mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) shifted the heroin dose-effect
      curve rightward and downward. Cannabinoid receptor agonists CP 55,940 and WIN
      55,212 enhanced the antinociceptive effects but not the discriminative stimulus
      or positive reinforcing effects of MU-opioid receptor agonists in rhesus monkeys,
      supporting the view that combining cannabinoid and opioid receptor agonists might
      result in enhanced treatment effectiveness for pain without similarly enhancing
      abuse and dependence liability.

PMID- 23536319
TI  - Opaciniols A-C, new terpenoids from Garcinia opaca.
AB  - Three new terpenoids, opaciniols A-C (1-3), were isolated from the barks of
      Garcinia opaca, together with malabarica-17,21-dien-3beta,14-diol (4) and 13betaH
      malabarica-14,17,21-trien-3beta-ol (5). Their structures were determined on the
      basis of NMR spectroscopic data. 3 and 4 showed moderate cytotoxicity against HL
      60 cells. 

PMID- 23536320
TI  - Non-nuclear localization of Ki-67 in human colorectal cancer cells grown as
      multicellular layers.
AB  - Multicellular layers (MCL) of cancer cells is an in vitro 3-dimensional (3D)
      model that mimics avascular microregions of human solid tumors and has been shown
      to be useful in pharmacokinetic-pharmacodynamic studies of anticancer agents. We
      investigated whether Ki-67, which is widely used as a proliferation marker, can
      be used to evaluate changes in proliferative fractions following drug exposure in
      MCL of HT-29 human colorectal cancer cells. Ki-67 expression was monitored and
      compared between cancer cells cultured as monolayers or MCL. Drug distribution
      and Ki-67 expression were evaluated within MCL following exposure to doxorubicin
      and paclitaxel. Ki-67 expression was observed in the nuclei of proliferating
      cells in monolayers, tumor xenograft, and multicellular spheroids. In MCL,
      however, Ki-67 expression was detected in the membrane/cytoplasm as well as in
      the nucleus throughout MCL. Neither the location nor the level of expression
      changed following drug exposure, whereas drug-induced apoptosis increased. Our
      data show that membranous/cytoplasmic Ki-67 may not be valid as a marker for the
      proliferative activity of cells grown as MCL. Studies for non-nuclear
      localization and its mechanism in 3D in vitro models of other cell lines are
      warranted.

PMID- 23536321
TI  - Clinical and prognostic significance of coagulation assays in gastric cancer.
AB  - PURPOSE: Activation of coagulation and fibrinolysis is frequently found among
      cancer patients. Such tumors are considered to be associated with a higher risk
      of invasion, metastases, and eventually, worse outcome. The aim of this study is
      to explore the clinical and prognostic value of blood coagulation tests in
      gastric cancer (GC) patients. MATERIALS AND METHODS: A total of 44 consecutive
      patients with a pathologically confirmed diagnosis of GC were enrolled into the
      study. Pretreatment blood coagulation tests including prothrombin time (PT),
      activated partial thromboplastin time (APTT), international normalized ratio
      (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were
      evaluated. Control group comprised 50 age- and sex-matched individuals without
      history of malignancy and coagulation disorder. RESULTS: Median age at diagnosis
      was 55 years, range 19-80 years; most had men (n = 32, 73 %) and metastatic
      disease (n = 31, 70 %). The level of blood coagulation tests showed a
      statistically significant difference between the patient and the control groups
      (P < 0.001 for all, but p = 0.07 for PT). DD levels were significantly associated
      with elevated PLT and LDH levels (p = 0.009 and p = 0.01, respectively). Patients
      with metastatic disease had higher levels of F (p = 0.001) and INR (p = 0.027)
      levels. Elevated DD levels tended to be a poor prognostic factor on outcome (p =
      0.06). CONCLUSION: Change in almost all coagulation tests are found in GC
      patients and only DD level seems to be of prognostic value.

PMID- 23536322
TI  - Properties of a tunable multinuclear nickel polyoxotungstate platform.
AB  - A series of hybrid nickel bisphosphonate (BP) polyoxometalates (POMs) has been
      isolated. The complexes NaK-Ni7-Ale2 (Ale = [H2O3PC(C3H6NH2)(OH)PO3H2]) and NaNH4
      Ni7-Ale2 are both made of two {PW9O34} fragments enclosing a heptanuclear Ni(II)
      core connected to two alendronate ligands. By pre-functionalising the alendronate
      moiety through the amino group, the naphthalene (napht) derivative Ni7
      (AleNapht)2 and the compounds Ni7-(AlePy2 Ni)2 (py = pyridyl) and Ni7-(AleAc2Ni)2
      (Ac = acyl) have been obtained. Compared with the NaK-Ni7-Ale2 species, these
      last two complexes contain two additional Ni(II) centres connected through two
      bis(2-pyridylmethyl)amine or two iminodiacetate groups, respectively. This
      results show that it is possible to functionalise the heptanuclear POM in a
      controlled manner. Quantification of the magnetic interactions in NaK-Ni7-Ale2
      revealed that in the {Ni7} core, ferromagnetic interactions are predominant, with
      a S = 5 ground state. Magnetisation versus dc field sweeps on a single crystal of
      NaK-Ni7-Ale2 exhibited hysteresis at low temperature. (1)H and (31)P NMR studies
      in aqueous solution performed on NaK-Ni7-Ale2 and Ni7-(AleNapht)2 evidenced that
      the PW9/Ni7/bisphosphonate assembly is stable in solution. This was completed by
      (31)P magic angle spinning (MAS) investigations and confirmed by (1)H DOSY
      experiments. The electrochemistry of these compounds proceeds through two well
      defined four-electron chemically reversible waves in a medium at pH 6. NaK-Ni7
      Ale2 proved to be efficient for the electrocatalytic reduction of nitrate,
      nitrite and nitrous oxide. Remarkably, its electrocatalytic efficiency for
      nitrate reduction is approximately three times higher than those previously
      reported for POMs in a medium at pH >4 under the same potential. The catalytic
      properties of two representatives of the hybrid family were also examined. It is
      shown that these nickel bisphosphonate polyoxotungstates are pre-catalysts for
      the oxidation of alcohols into ketones or carboxylic acids, depending on the
      classes of alcohols considered, the stoichiometric oxidant used being H2O2.
      Noticeably, it has been found that an analogous cobalt bisphosphonate
      polyoxotungstate complex does not present any related activity, highlighting the
      crucial role of the 3d cations on the catalytic process.

PMID- 23536323
TI  - Thrombolysis of basilar artery occlusion: impact of baseline ischemia and time.
AB  - OBJECTIVE: To evaluate the impact of extensive baseline ischemic changes on
      functional outcome after thrombolysis of basilar artery occlusion (BAO), and to
      study the effect of time to treatment in the absence of such findings. METHODS:
      We prospectively evaluated 184 consecutive patients with angiography-proven BAO.
      The majority of patients received intravenous alteplase and concomitant full-dose
      heparin. Extensive baseline ischemia was defined as posterior circulation Acute
      Stroke Prognosis Early CT score (pc-ASPECTS) < 8. Onset-to-treatment time (OTT)
      was evaluated both as a continuous and as a categorical variable (0-6 hours, 6-12
      hours, 12-24 hours, and 24-48 hours). Successful recanalization means
      thrombolysis in myocardial infarction (TIMI) = 2 to 3. Symptomatic intracranial
      hemorrhage (sICH) was evaluated with National Institute of Neurological Disorders
      and Stroke, European Cooperative Acute Stroke Study II, and Safe Implementation
      of Thrombolysis in Stroke criteria. Poor 3-month outcome was defined as modified
      Rankin Scale score of 3 to 6. RESULTS: The majority (96%) of patients with
      baseline pc-ASPECTS < 8 had poor 3-month outcome, and a similar number (94%) was
      observed in those of them with confirmed recanalization (51.5%). In contrast,
      half of the patients with pc-ASPECTS >= 8 and successful recanalization (73.2%)
      achieved good outcome. In these patients, OTT was associated with poor outcome
      neither as a continuous nor as a categorical variable. Factors independently
      associated with poor outcome were greater age and baseline National Institutes of
      Health Stroke Scale, lack of recanalization, history of atrial fibrillation, and
      sICH. In the model including the whole cohort (patients with any pc-ASPECTS), pc
      ASPECTS < 8 was independently associated with poor outcome (odds ratio = 5.83,
      95% confidence interval = 1.09-31.07). INTERPRETATION: In the absence of
      extensive baseline ischemia, recanalization of BAO up to 48 hours was seldom
      futile and produced good outcomes in 50% of patients, which was independent of
      time to treatment.

PMID- 23536325
TI  - Experimental hypothyroidism during pregnancy affects nociception and locomotor
      performance of offspring in rats.
AB  - BACKGROUND: Thyroid hormones (THs) play a crucial role in the development of
      several organic systems. An adequate support of maternal THs may be required to
      ensure a normal nociceptive function of offspring into adulthood. We investigated
      the impact of experimental gestational hypothyroidism (EGH) on nociceptive
      threshold and motor performance in the offspring at different post-natal days
      (PND) in both male and female rats. METHODS: EGH was induced by the
      administration of 0.02% methimazole (MMI) in the drinking water from the ninth
      day of gestation until birth. The offspring from MMI-treated dams (OMTDs) or from
      water-treated dams (OWTDs) were assessed for thermal and mechanical nociception
      using the tail-flick test and von Frey filaments, respectively. Both rota-rod and
      grip strength were used to assess motor function. RESULTS: OMTD had reduced
      thermal (p<0.05) but not mechanical threshold at all studied ages (60 and 120
      PND). Sixty-day-old OMTD presented reduced latency to the tail-flick test
      (p=0.01). Grip strength in 120-day-old OMTD was reduced (p<0.01). However, only
      male OMTD presented a lower locomotor performance on the rota-rod test when
      analysed on the 60th PND (p<0.01). CONCLUSIONS: EGH promotes hypersensitivity to
      noxious thermal but not mechanical stimulus. Moreover, motor force is similarly
      reduced in male and female OMTDs, whereas motor performance is reduced only in
      mature male OMTD, suggesting the presence of a protective factor in females.

PMID- 23536324
TI  - 2012 consensus document of the Italian Society of Hypertension (SIIA): strategies
      to improve blood pressure control in Italy: from global cardiovascular risk
      stratification to combination therapy.
AB  - Observational clinical studies have demonstrated that only 30-40% of patients
      with arterial hypertension achieve the recommended blood pressure goals (below
      140/90 mmHg). In contrast, interventional trials consistently showed that it is
      possible to achieve effective blood pressure targets in about 70% of treated
      hypertensive patients with different cardiovascular risk profiles, especially
      through the use of rational, effective and well tolerated combination therapies.
      In order to bridge the gap between current and desired blood pressure control and
      to achieve more effective prevention of cardiovascular diseases, the Italian
      Society of Hypertension (SIIA) has developed an interventional strategy aimed at
      reaching nearly 70% of treated controlled hypertensive patients by 2015. This
      ambitious goal can be realistically achieved by a more rational use of modern
      tools and supports, and also through the use of combination therapy in
      hypertension in daily clinical practice, especially if this approach can be
      simplified into a single pill (fixed combination therapy), which is a therapeutic
      option now also available in Italy. Since about 70-80% of treated hypertensive
      patients require a combination therapy based on at least two classes of drugs in
      order to achieve the recommended blood pressure goals, it is of key importance to
      implement this strategy in routine clinical practice. Amongst the various
      combination therapies currently available for hypertension treatment and control,
      the use of those strategies based on drugs that antagonize the renin-angiotensin
      system, such as angiotensin II type 1 receptor antagonists (angiotensin receptor
      blockers) and ACE inhibitors, in combination with diuretics and/or calcium
      channel blockers, has been shown to significantly reduce the risk of major
      cardiovascular events and to improve patient compliance to treatment, resulting
      in a greater antihypertensive efficacy and better tolerability compared with
      monotherapy. The present document of the Italian Society of Arterial Hypertension
      (SIIA) aims to gather the main indications for the implementation of combination
      therapy in the treatment of hypertension, in order to improve blood pressure
      control in Italy.

PMID- 23536327
TI  - Reply: To PMID 22987690.

PMID- 23536328
TI  - Depressive symptoms in bereaved parents in the 2008 Wenchuan, China earthquake: a
      cohort study.
AB  - This study sought to expand the literature on bereavement and response to natural
      disasters by reporting the prevalence, severity, and correlates of depressive
      symptoms among bereaved and nonbereaved parents of the 2008 Wenchuan Earthquake
      in China. Bereaved (n = 155) and nonbereaved (n = 35) parents from the Xiang'e
      township in China were interviewed at 18 months (Wave 1) and 24 months (Wave 2)
      following the earthquake. From Wave 1 to Wave 2, rates of probable depression
      fell for both bereaved (65.8% to 44.5%) and nonbereaved parents (34.3% to 20.0%).
      The depression index of both groups also decreased, but only significantly among
      bereaved parents. Of bereaved parents, those with fewer years of education had
      more severe symptoms at both waves. Depressive symptom severity of bereaved
      mothers improved over time, but that of bereaved fathers remained unchanged. Not
      becoming pregnant again after the earthquake was significantly linked to worse
      depressive symptoms in both waves, but this was not significant when age was
      added to the model. Bereaved parents may need more postearthquake supportive
      services, with fathers, individuals with fewer years of education, and parents
      who are not able to become pregnant again after the earthquake being particularly
      vulnerable.

PMID- 23536326
TI  - Therapeutic approaches for shankopathies.
AB  - Despite recent advances in understanding the molecular mechanisms of autism
      spectrum disorders (ASD), the current treatments for these disorders are mostly
      focused on behavioral and educational approaches. The considerable clinical and
      molecular heterogeneity of ASD present a significant challenge to the development
      of an effective treatment targeting underlying molecular defects. Deficiency of
      SHANK family genes causing ASD represent an exciting opportunity for developing
      molecular therapies because of strong genetic evidence for SHANK as causative
      genes in ASD and the availability of a panel of Shank mutant mouse models. In
      this article, we review the literature suggesting the potential for developing
      therapies based on molecular characteristics and discuss several exciting themes
      that are emerging from studying Shank mutant mice at the molecular level and in
      terms of synaptic function.

PMID- 23536329
TI  - Everyday physical activity in ambulatory heart transplant candidates: the role of
      expected health benefits, social support, and potential barriers.
AB  - BACKGROUND: Physical activity (PA) is recommended for stable patients with
      advanced heart failure (HF). PURPOSE: We evaluated expected health benefits of PA
      and social support as facilitators of PA, and physical symptom distress and
      psychological distress (depression, anxiety) as barriers to PA. Additionally, we
      investigated if facilitators of PA are of particular importance for patients who
      report barriers. METHOD: We analyzed data assessed at time of waitlisting in 231
      ambulatory patients (53.4 +/- 10.3 years, 18 % women) who were enrolled in the
      multisite Waiting for a New Heart Study in 1 Austrian and 16 German hospitals.
      Self-reported everyday PA scores (number of activities, duration of activities)
      was regressed on demographic characteristics and indicators of disease severity
      (ejection fraction, peak oxygen consumption), facilitators (expected health
      benefits of PA, perceived emotional support, perceived support for PA), and
      barriers to PA (physical symptom distress, psychological distress). Interaction
      terms of facilitators with barriers were also examined. RESULTS: PA was
      positively associated with higher peak oxygen consumption, validating self
      reported PA. Regarding facilitators, expected health benefits of PA were
      independently associated with higher PA (p values < 0.001). There were no main
      effects for social support on PA. Regarding barriers, depression tended to be
      associated with fewer activities (p = 0.068). However, in the presence of
      barriers (depression, physical symptoms), feeling supported for being physically
      active was positively associated with PA (p values < 0.05). CONCLUSION:
      Interventions to improve PA may benefit from strengthening positive expectations
      of health outcomes associated with everyday PA and fostering PA-specific social
      support for those distressed by HF symptoms or depression.

PMID- 23536330
TI  - Systematic review and meta-analysis of intraoperative peritoneal lavage for
      colorectal cancer staging.
AB  - BACKGROUND: Intraperitoneal cancer cells are detectable at the time of colorectal
      cancer resection in some patients. The significance of this, particularly in
      patients with no other adverse prognostic features, is poorly defined.
      Consequently peritoneal lavage is not part of routine practice during colorectal
      cancer resection, in contrast with other abdominal malignancies. The aim of this
      systematic review was to determine the effect of positive intraoperative
      peritoneal cytology on cancer-specific outcomes in colorectal cancer. METHODS: A
      systematic review of key electronic journal databases was undertaken using the
      search terms 'peritoneal cytology' and 'colorectal' from 1980 to 2012. Studies
      including patients with frank peritoneal metastasis were excluded. Meta-analysis
      for overall survival, local/peritoneal recurrence and overall recurrence was
      performed. RESULTS: Twelve cohort studies (2580 patients) met the inclusion
      criteria. The weighted mean yield was 11.6 (range 2.2-41) per cent. Yield rates
      were dependent on timing of sampling (before resection, 11.8 per cent; after
      resection, 13.2 per cent) and detection methods used (cytopathology, 8.4 per
      cent; immunocytochemistry, 28.3 per cent; polymerase chain reaction, 14.5 per
      cent). Meta-analysis showed that positive peritoneal lavage predicted worse
      overall survival (odds ratio (OR) 4.26, 95 per cent confidence interval 2.86 to
      6.36; P < 0.001), local/peritoneal recurrence (OR 6.57, 2.30 to 18.79; P < 0.001)
      and overall recurrence (OR 4.02, 2.24 to 7.22; P < 0.001). CONCLUSION: Evidence
      of intraoperative peritoneal tumour cells at colorectal cancer resection is
      predictive of adverse cancer outcomes.

PMID- 23536331
TI  - Knocking out DJ-1 attenuates astrocytes neuroprotection against 6-hydroxydopamine
      toxicity.
AB  - Astrocytes are the most abundant glial cell type in the brain. Impairment in
      astrocyte functions can critically influence neuronal survival and leads to
      neurodegeneration. Parkinson's disease (PD) is a common neurodegenerative
      disorder, characterized by motor dysfunction that results from progressive
      neuronal loss. Astrocytic dysfunction was demonstrated in human samples and in
      experimental models of PD. Mutations in DJ-1 (PARK7) leading to loss of
      functional protein cause familial PD and enhance sensitivity to oxidative
      insults. Recently, an increase in DJ-1's expression was found in reactive
      astrocytes in various neurodegenerative disorders. Here we show that lack of DJ-1
      attenuates astrocytes' ability to support neuronal cells, thereby leading to
      accelerated neuronal damage. DJ-1 knockout mice demonstrated increased
      vulnerability in vivo to 6-hydroxydopamine (6-OHDA) hemiparkinsonian PD model.
      Astrocytes isolated from DJ-1 knockout mice showed an inferior ability to protect
      human neuroblastoma cells against 6-OHDA insult both by co-culture and through
      their conditioned media, as compared to wild-type astrocytes. DJ-1 knockout
      astrocytes showed blunted ability to increase the expression of cellular
      protective mechanisms against oxidative stress mediated via Nrf-2 and HO-1 in
      response to exposure to 6-OHDA. These experiments demonstrated that lack of DJ-1
      impairs astrocyte-mediated neuroprotection.

PMID- 23536332
TI  - Self-assembly of ambidentate pyridyl-carboxylate ligands with octahedral
      ruthenium metal centers: self-selection for a single-linkage isomer and
      anticancer-potency studies.
AB  - The synthesis of six new [2+2] metallarectangles through the coordination-driven
      self-assembly of octahedral Ru(II)-based acceptors with ambidentate pyridyl
      carboxylate donors is described. These molecular rectangles are fully
      characterized by (1)H NMR spectroscopy, high-resolution electrospray mass
      spectrometry, and single-crystal X-ray diffraction. In each case, despite the
      possible formation of multiple isomers, based on the relative orientation of the
      pyridyl and carboxylate groups (head-to-head versus head-to-tail), evidence for
      the formation of a single preferred ensemble (head-to-tail) was found in the (1)H
      NMR spectra. Furthermore, the cytotoxicities of all of the rectangles were
      established against A549 (lung), AGS (gastric), HCT-15 (colon), and SK hep 1
      (liver) human cancer cell lines. The cytotoxicities of rectangles that contained
      the 5,8-dihydroxy-1,4-naphthaquinonato bridging moiety between the Ru centers (9
      11) were particularly high against AGS cancer cells, with IC50 values that were
      comparable to that of reference drug cisplatin.

PMID- 23536333
TI  - Editorial.

PMID- 23536334
TI  - [Consensus and controversy of surgical diagnosis and treatment for
      gastrointestinal stromal tumor].
AB  - At the end of 2012, Chinese Society of Clinical Oncology (CSCO) amended and
      revised the expert consensus of gastrointestinal stromal tumor (GIST) 2011. This
      article is respectively review hot topics regarding surgical intervention during
      the revision, including principles and indications of biopsy and surgery.

PMID- 23536335
TI  - [Standard of postoperative risk assessment for resectable gastrointestinal
      stromal tumor and its evaluation].
AB  - Surgery is the only possible cure protocol of gastrointestinal stromal tumor
      (GIST). But the risk of recurrence exists constantly. Risk assessment of relapse
      is very important to guide the targeted adjuvant therapy and predict the
      prognosis. Although the variables and grading in the risk assessment of
      recurrence after complete resection of primary local GIST have been identified,
      but either the F/NIH consensus, AFIP standards, modified NIH standards, or risk
      identification methods attempted to apply mathematical calculation model in
      recent years, including Jason S Gold risk nomogram, Rossi nomogram, Joensuu high
      Hotline Dengjun, are short of long-term, large-scale clinical trials without
      selection bias. Therefore, recurrence risk probability cannot be predicted
      accurately.

PMID- 23536336
TI  - [Application and value of mutation detection in diagnosis and treatment of
      gastrointestinal stromal tumor].
AB  - Mutation of c-kit and platelet-derived growth factor receptor alpha (PDGFRA) is
      the most important molecular feature of gastrointestinal stromal tumor (GIST).
      Mutation detection of these two genes is of great significance when establishing
      the diagnosis of a kit-negative GIST, or when predicting response to tyrosine
      kinase inhibitor. Furthermore, more and more researches focus on the feasibility
      of the mutation status using as a prognostic factor in recent years.

PMID- 23536337
TI  - [New prospective on adjuvant treatment for gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal
      tumor of the gastrointestinal tract. With decades of development, surgical
      excision combined with molecular targeted agents is becoming the mode for the
      GIST treatment. Imatinib mesylate (IM) is the first-line therapy medicine for
      GIST adjuvant treatment, and it significantly reduces recurrence or metastasis
      and increases survival. According to the recently results of SSGXVIII/AIO study,
      imatinib adjuvant therapy should be administered for at least 3 years for the
      GIST patients with a high estimated risk of recurrence and metastasis after
      surgery. Nevertheless, the optimal duration of the adjuvant therapy or the follow
      up policy remains unclear, and we look forward to standard assessment criteria
      for individualized treatment.

PMID- 23536338
TI  - [Efficacy observation on imatinib adjuvant therapy with longer duration in
      patients with gastrointestinal stromal at intermediate or high risk of
      recurrence].
AB  - OBJECTIVE: To evaluate the recurrence-free survival (RFS) and safety of imatinib
      adjuvant therapy with longer treatment duration in patients undergoing complete
      resection of localized primary gastrointestinal stromal tumor (GIST). METHODS:
      Clinical and follow-up data of 101 GIST patients between March 2004 and May 2009
      with intermediate or high recurrence risk receiving imatinib adjuvant treatment
      and more than 3 years follow-up time in Peking University Cancer Hospital were
      retrospectively analyzed. Imatinib adjuvant treatment: 3 patients discontinued
      less than 1 year imatinib treatment because of adverse events; 24, 21 and 18
      patients discontinued imatinib after 1 year, 2 years, and 3 years treatment; 8
      patients received 3 years adjuvant treatment and were ongoing; 27 patients
      received more than 4 years imatinib adjuvant treatment. RESULTS: The median
      follow-up time was 60 months (95%CI:57.9-62.1). Nineteen patients had GIST
      recurrence, of whom recurrence happened during imatinib adjuvant therapy in 5
      patients and after imatinib treatment in 14 patients. The median period from
      imatinib stopping to recurrence was 12.0 months (95%CI:9.6-14.4). Patients with
      recurrent GIST achieved tumor control after imatinib resumption. RFS of patients
      (n=53) with >=3 years imatinib treatment duration was higher than that of
      patients (n=48) with <3 years imatinib duration (93.9% vs. 68.0%, P<0.01). In
      addition, prolonged adjuvant imatinib duration did not significantly increase the
      adverse events related to treatment (P>0.05). CONCLUSIONS: Prolonged adjuvant
      imatinib duration may further improve RFS rate further in patients with
      intermediate or high risk of recurrence after complete tumor resection without
      increased adverse events.

PMID- 23536339
TI  - [Efficacy and safety of sunitinib on patients with imatinib-resistant
      gastrointestinal stromal tumor].
AB  - OBJECTIVE: To investigate the efficacy and safety of sunitinib on the management
      of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.
      METHODS: Clinical data of 48 patients with imatinib-resistant GIST received
      sunitinib therapy from May 2008 to April 2012 in the Union Hospital of Fujian
      Medical University were analyzed retrospectively. Eighteen patients received 50
      mg/d of sunitinib in a protocol of 4/2 (4 weeks on and 2 weeks off) [50 mg/d
      (4/2)], and 30 patients received a protocol of 37.5 mg of sunitinib continuous
      daily dose (37.5 mg/d CDD). RESULTS: The median duration of sunitinib
      administration of all the 48 patients was 56 weeks, and the short-term efficacy
      was evaluated at 24 weeks after the initial treatment according to the Choi
      criteria. The response rate was 27.1% (13/48), including 1 case with complete
      response (CR), 12 cases with partial response (PR), and 21 cases with stationary
      disease (SD). The disease control rate was 70.8% (34/48). The mean follow-up time
      of 48 patients was 89 weeks. The median progression-free survival (PFS) and
      overall survival (OS) were 48 weeks and 92 weeks respectively. Stratified
      analyses indicated that the median PFS of patients previously treated by imatinib
      400 mg/d and >400 mg/d were 53 weeks and 35 weeks respectively (P=0.018), and the
      median OS of these two groups were 157 weeks and 71 weeks respectively (P=0.003).
      Patients with exon 11 mutations had a significantly shorter OS compared with
      those with exon 9 mutations (71 weeks vs 157 weeks, P=0.008). Hand-foot syndrome
      was the most common adverse effect (25/48, 52.1%), followed by nausea (24/48,
      50.0%), fatigue (23/48, 47.9%), neutropenia(21/48, 41.7%). The sub-group analysis
      of two protocols of sunitinib administration showed that the incidence of
      diarrhea and hand-foot syndrome were higher in 50 mg/d (4/2) group than those in
      37.5 mg/d CDD group (P=0.027, P=0.048). CONCLUSIONS: Sunitinib is effective for
      the patients with imatinib-resistant GIST. After 400 mg/d imatinib treatment
      failure, sunitinib should be prescribed instead of increased dosage of imatinib.
      Patients with KIT exon 9 mutations present better prognosis than those with KIT
      exon 11 mutations. The protocol of sunitinib 37.5 mg/d CDD possesses better
      safety.

PMID- 23536340
TI  - [Application of perioperative imatinib mesylate therapy in initial resectable
      primary local advanced gastrointestinal stromal tumor at intermediate or high
      risk].
AB  - OBJECTIVE: To evaluate the effect of perioperative imatinib mesylate (IM) therapy
      for patients with initial resectable primary local advanced gastrointestinal
      stromal tumor (GIST) at intermediate or high risk on R0 resection rate and the
      prognosis. METHODS: Forty-eight above GIST patients between December 2001 and
      February 2012 were divided into 2 groups: neoadjuvant group (15 cases, pre- and
      post-operation IM therapy) and adjuvant group (33 cases, post-operative IM
      therapy). R0 resection rate, complication rate, disease-free survival (DFS) and
      overall survival (OS) were analyzed and compared between the two groups. RESULTS:
      The maximal tumor diameter and average tumor diameter were larger in neoadjuvant
      group as compared to adjuvant group (11.2 cm vs. 7.7 cm, P=0.005; 9.1 cm vs. 6.2
      cm, P=0.014). The response rate of preoperative IM therapy was 93.3% (14/15). The
      R0 resection rate was 86.7% and 84.8% (P=1.000), and the complication rate was
      13.3% and 9.1% (P=0.642) in neoadjuvant and adjuvant group respectively. The 3
      year DFS was 55% and 41% (P=0.935), and 5-year OS was 83% and 75% (P=0.766) in
      neoadjuvant and adjuvant group respectively. CONCLUSIONS: Resectable primary
      local advanced GIST at intermediate or high risk with larger tumor diameter
      receiving perioperative IM therapy can achieve the same R0 resection rate,
      complication rate, DFS and OS as the GIST with smaller diameter receiving
      operation first. Perioperative IM therapy has potential advantage.

PMID- 23536341
TI  - [Value of computed tomography features for prognosis evaluation of
      gastrointestinal stromal tumor].
AB  - OBJECTIVE: To analyze the association between CT features and survival rate of
      GIST, and to elucidate the significance of CT features for prognosis. METHODS:
      Clinical data of 38 patients with pathologically and immunohistochemically proven
      GISTs, including 11 patients at high biological risk, 13 at moderate risk, 10 at
      low risk and 4 at very low risk. Patients who underwent CT examination for
      primary tumors were included. Association between CT features and survival rate
      was examined. RESULTS: The mean follow-up period of 38 cases was 42.6 months and
      the 3-year survival rate was 86.8%. Univariate analysis revealed that tumor
      growth pattern, diameter, lobulated shape, irregular margin, necrosis,
      ulceration, adjacent invasion, and liver metastasis were associated factors of 3
      year survival rate. Circumference invasion and hepatic metastases predicted poor
      3-year survival rate (P<0.05). Calcification and intensity were not associated
      with prognosis (P>0.05). CONCLUSIONS: CT can demonstrate the tumor growth
      pattern, size, shape, boundary, density, necrosis, hemorrhage, calcification,
      ulcer, enhance features and metastasis. CT can play an important role in
      estimating the survival rate of GIST.

PMID- 23536342
TI  - [Clinicopathological features and management of gastrointestinal stromal tumors
      complicated with synchronous other alimentary malignant tumor].
AB  - OBJECTIVE: To explore the clinicopathologic features, treatment and prognosis of
      gastrointestinal stromal tumor (GIST) complicated with synchronous other
      alimentary malignant tumors. METHODS: Clinical data of 525 patients with GIST
      undergoing surgical treatment from August 2004 to November 2012 in Shanghai Renji
      Hospital were reviewed retrospectively, among whom 46 patients presented
      synchronous other alimentary malignancy. RESULTS: GIST and other alimentary
      malignancy coexisting cases were less likely to be screened out preoperatively
      (2.2%, 1/46) and associated with elder age (P=0.001), more likely arise from
      stomach (P=0.000), smaller tumor maximum diameter (P=0.000), and lower mitotic
      count (P=0.000). According to NIH postoperative risk classification, there were
      36 at very low risk, 9 at low risk, and 1 at high risk. Although the risk of GIST
      recurrence was lower for GIST and other alimentary malignancy coexisting cases,
      their 5-year survival rate was lower than that of patients with GIST alone
      (36.1%VS. 82.2%, P=0.000). CONCLUSIONS: GIST patients complicated with
      synchronous alimentary malignant tumor are usually low or very low risk and has
      minimal impact on the prognosis. Survival depends primarily on the synchronous
      alimentary malignant tumors. Therefore, it is reasonable to lay emphasis on the
      treatment of the alimentary malignant tumor, and perform synchronous resection of
      GIST if possible.

PMID- 23536343
TI  - [Clinicopathological characteristics and surgical treatment of duodenal
      gastrointestinal stromal tumor].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics and surgical
      treatment of duodenal gastrointestinal stromal tumor (GIST). METHODS:
      Clinicopathological data of 25 cases with duodenal GIST from January 2007 to July
      2011 in West China hospital were retrospectively analyzed. RESULTS: All the
      patients were identified by pathological examination without specific symptoms.
      Tumors were located in the bulb area in 2 cases, descending portion in 11 cases,
      transverse portion in 8 cases, and ascending portion in 4 cases. Two cases were
      at very low risk, 7 at low risk, 6 at intermediate risk, and 10 at high risk. All
      the patients received surgical resection, including 11 pancreaticoduodenectomies,
      10 local tumor resections, 2 duodenal segmental resections, and 2 distal subtotal
      gastrectomies. Eighteen patients were followed up from 16 to 39 months and 3
      patients recurred 18, 30, and 35 months after operation respectively.
      CONCLUSIONS: Duodenal GIST exhibits no distinct clinical characteristics.
      Complete removal of the tumor is the main choice of treatment.

PMID- 23536344
TI  - [Study on associated biomarkers influencing recurrence, metastasis and prognosis
      in patients with gastrointestinal stromal tumors after complete resection].
AB  - OBJECTIVE: To explore the associated biomarkers influencing recurrence,
      metastasis and prognosis in patients with gastrointestinal stromal tumors (GIST)
      after complete resection. METHODS: Tumor tissue samples of 148 patients with GIST
      undergoing complete resection from January 1990 to December 2008 in Sun Yat-sen
      University Cancer Center were collected. The expressions of Ki-67, E-cadherin,
      MMP7, CD44, nm23, P53, survivin, Cyclin D1, COX-2, and VEGF in tumor tissue
      samples were detected by tissue microarray and immunohistochemistry (IHC). The
      association of above factors expressions with recurrence, metastasis and
      prognosis was examined. RESULTS: Log-rank test showed that Ki-67, E-cadherin,
      MMP7, CD44, P53 and survivin were associated to disease-free duration after
      complete GIST resection (all P<0.05), and the Ki-67, E-cadherin, P53 and survivin
      were associated to overall survival (all P<0.05). Cox multivariate analysis
      revealed that disease-free survival was associated with Ki-67, CD44 and P53 (all
      P<0.05), and the overall survival was only associated with Ki-67 (P<0.05).
      CONCLUSION: Ki-67, CD44 and P53 are closely associated with recurrence and
      metastasis after complete GIST resection, and Ki-67 can predict the prognosis of
      GIST.

PMID- 23536345
TI  - [Prognosis analysis of 247 cases of gastrointestinal stromal tumor].
AB  - OBJECTIVE: To study the clinicopathologic features and prognostic factors of
      gastrointestinal stromal tumor (GIST). METHODS: Clinicopathologic data of 247
      patients with GIST from January 2003 to November 2012 in the Affiliated Hospital
      of Qingdao University Medical College, and the prognostic factors were evaluated
      retrospectively by univariate and multivariate analysis with Log-rank test and
      Cox proportional hazard model. RESULTS: Patients were followed up with a median
      time of 26 months (1 to 113 months). Twenty-six patients developed recurrence or
      metastasis, and 18 died of GIST. The 1-, 3-, 5-year survival rates were 94%, 91%
      and 83% respectively. Univariate analysis showed that age, tumor location, tumor
      size, mitotic count and tumor rupture were predictive factors of survival after
      resection of primary GIST (all P<0.01). For patients at intermediate and high
      risk to relapse, imatinib group had a higher 5-year overall survival rate than
      non-imatinib group (85.7% vs. 81.0%, P<0.05). Multivariate analysis revealed that
      tumor size (RR=2.248, 95%CI:1.081-4.677, P=0.030), mitotic count (RR=2.220,
      95%CI:1.032-4.776, P=0.041) and tumor rupture (RR=5.183, 95%CI:1.677-16.017,
      P=0.004) were independent prognostic factors. CONCLUSIONS: Tumor size, mitotic
      count and tumor rupture affect the prognosis after resection of primary GIST
      independently. Imatinib adjuvant therapy can improve overall survival of patients
      at intermediate and high risk to relapse after surgery.

PMID- 23536346
TI  - [Clinical characteristics and prognostic analysis of 45 patients with high-risk
      gastrointestinal stromal tumors].
AB  - OBJECTIVE: To investigate the clinical characteristics and prognosis factors of
      primary resectable high-risk gastrointestinal stromal tumors (GIST). METHODS: The
      clinicopathological and follow-up data of 45 patients with primary resectable
      high-risk gastrointestinal stromal tumors between January 2002 and November 2010
      were retrospectively reviewed. RESULTS: Forty-five patients included 18 males and
      27 females with a median age of 48 years (range, 28-77 years). Of 45 tumors, 19
      (42.2%) located in the stomach, 9 (20.0%) in the small intestine, 7 (15.6%) in
      the rectum, 4 (8.9%) in the mesentery, and 6 (13.3%) in the retroperitoneum. All
      the patients received surgical resection and 35 (77.8%) underwent complete
      resection, 10 (22.2%) underwent resection of ruptured tumors (before or during
      operation), 33 (73.3%) underwent R0 resection, 5 (11.1%) underwent R1 resection,
      and 7 (15.6%) underwent R2 resection. All the patients received targeted therapy
      of imatinib after surgery. The median duration of imatinib was 24 (10-99) months.
      The main side effect was noticed in all the patients, mainly including edema in
      39 (86.7%) patients and leukopenia in 27 (60.0%) patients. The relapse rate was
      37.8% (17/45). The 1-, 3-, and 5-year survival rates were 100%, 86.7% and 74.4%,
      respectively. Univariate and multivariate analysis revealed that the degree of
      resection was independently associated with the prognosis of high-risk GIST
      patients. CONCLUSIONS: Surgery is effective treatment for the GIST. Efforts to
      obtain R0 resection are important to improve the efficacy of primary resectable
      high-risk GIST.

PMID- 23536347
TI  - [Expression of DOG-1 in gastrointestinal stromal tumors and its significance].
AB  - OBJECTIVE: To identify the expression of DOG-1 in gastrointestinal stromal tumors
      (GIST) and to explore its potential association with clinicopathological features
      of GIST. METHODS: Two tissue microarrays (TMA) were used for the study. Each TMA
      contained 80 tissue samples of GIST from 80 different patients, with each tumor
      represented by one core, and paraffin-embedded sections of 40 samples from normal
      gastrointestinal tissue were used as control. Immunohistochemistry staining (SABC
      method) was performed on TMA and paraffin-embedded sections to detected the
      expression of c-Kit (CD117) and DOG-1. RESULTS: Immunohistochemistry showed that
      in 80 GIST patients, 76 cases (95.0%) were DOG-1 positive and 67 cases (83.8%)
      were CD117 positive. The positive rate of DOG-1 was higher than that of CD117
      (P<0.05). In 13 GIST samples of negative CD117, the positive rate of DOG-1 was
      100%. Expressions of both DOG-1 and CD117 were negative in all the 40 samples of
      normal gastrointestinal tissue. The positive expression of DOG-1 and CD117 was
      not significantly different in spindle cell type (96.0% vs. 96.0%, P>0.05) and in
      mixed cell type (91.7% vs. 75.0%, P>0.05). While in the epithelioid cell type,
      the DOG-1 expression was higher than CD117 expression (94.1% vs. 52.9%, P<0.05).
      The positive expression of DOG-1 and CD117 was not associated with age, gender,
      location and risk stratification of the tumors (all P>0.05). CONCLUSIONS: DOG-1
      expression is up-regulated in gastrointestinal stromal tumors, especially in
      epithelioid cell GIST, and may be used as a new marker in the diagnosis of GIST.

PMID- 23536348
TI  - [Analysis of clinicopathologic characteristics and prognosis on mixed histology
      type of gastric cancer].
AB  - OBJECTIVE: To evaluate the clinicopathologic characteristics and prognosis of
      mixed histological type (MHT) gastric cancer. METHODS: Clinical and follow-up
      data of 1108 gastric cancer patients undergoing radical operation in Tianjin
      Cancer Hospital between 2003 and 2006 were analyzed retrospectively.
      Clinicopathologic characteristics of MHT gastric cancer were summarized and the
      prognosis was analyzed by Kaplan-Meier analysis and COX regression. RESULTS:
      Among the 1108 patients, 144 (13.0%) had mixed histology type of gastric cancer.
      Compared to the unitary histological type (UHT), MHT gastric cancer had bigger
      tumor size, higher proportion of T4 tumor, and was easier for lymph node and
      distant metastasis (all P<0.05). The 3- and 5-year survival rates of patients
      with MHT were 26.5% and 10.8% respectively, which were lower than those with UHT
      (58.8% and 35.0%, P<0.01). Univariate and multivariate analyses showed TNM
      classification was an independent prognostic factor (P<0.01). CONCLUSIONS: MHT
      gastric cancer shows worse prognosis than UHT gastric cancer. There is no
      difference in prognosis among various combination of MHT gastric cancer. TNM
      classification is an independent prognostic factor of MHT gastric cancer.

PMID- 23536349
TI  - [Short-term efficacy comparison of complete mesocolic excision and traditional
      colon cancer resection].
AB  - OBJECTIVE: To investigate the short-term efficacy of complete mesocolic excision
      (CME). METHODS: Clinical data of 62 cases of colon cancer (I-III phase) with
      radical resection including CME surgery group of 31 cases and traditional surgery
      group of 31 cases from January 2011 to October 2011 in Peking University People's
      Hospital were retrospective analyzed. RESULTS: The number of removed lymph node
      in CME and traditional resection group was 22.5+/-1.8 and 17.6+/-1.3 respectively
      (P<0.05) and the positive rate of lymph node in mesentery root was 9.7% (3/31) in
      CME surgery group. Operative blood loss was (123.5+/-17.6) ml and (143.5+/-15.3)
      ml in CME and traditional resection group without significant difference
      (P>0.05). Except for more abdominal drainage volume of 3 days post-operation in
      CME group (P<0.05), the postoperative recovery indicators of postoperative
      drainage tube removed time, exhaust time, eating time, and the socioeconomic
      effects indicators of postoperative hospitalization, hospitalization costs were
      not significantly different between two groups (all P>0.05). Postoperative
      intestinal obstruction occurred in 3 cases and 4 cases, lymph fistula in 2 cases
      and 0 case, wound dehiscence in 1 case and 1 case in CME group and traditional
      resection group respectively. Postoperative complication rate was not
      significantly different (19.4% vs. 16.1%, P>0.05). CONCLUSION: Compared with
      traditional radical surgery, CME sweeps lymph nodes more thoroughly, including
      lymph nodes of mesocolic roots, and does not affect postoperative recovery and
      increase the risk of postoperative complications.

PMID- 23536350
TI  - [Application of simplified intensity modulated radiation therapy in gastric
      cancer after operation].
AB  - OBJECTIVE: To elucidate the application and the dosimetry characteristic of the
      simplified intensity modulated radiation therapy (sIMRT) for gastric cancer after
      operation, and to compare the dose distribution with intensity modulated
      radiation therapy (IMRT) and three-dimension conformal radiation therapy (3D
      CRT). METHODS: Twelve patients with gastric cancer after operation were enrolled
      in this study. 3D-CRT plan, 5-field IMRT plans (20 degree, 80 degree, 180 degree,
      280 degree, 340 degree) and 5-field sIMRT plans (20 degree, 80 degree, 180
      degree, 280 degree, 340 degree) were performed for each patient. The conformal
      index (CI), heterogeneity index (HI) of the planning target volume (PTV) and the
      dose of normal organs were analyzed with the dose volume histogram (DVH). The
      total MU and treatment time were also compared. RESULTS: The sIMRT and IMRT plans
      had comparable CI (sIMRT>IMRT>3D-CRT), and showed better dose conformity but
      worse homogeneity than 3D-CRT. The percentage of volume receiving 20 Gy, 25 Gy,
      30 Gy and 40 Gy by liver were significantly lower in sIMRT than that in 3D-CRT,
      and comparable to IMRT. All the dose volumes to kidneys with sIMRT were still
      significantly lower as compared to 3D-CRT, and comparable to IMRT. The sIMRT plan
      was better than IMRT plan in total MU and treatment time. CONCLUSIONS: sIMRT has
      comparable dose distribution in patients with gastric cancer to IMRT, but is
      significantly better than 3D-CRT. Treatment time of sIMRT is the shortest. So
      sIMRT technique can be applied more simply.

PMID- 23536351
TI  - [Impact of sleeve gastrectomy with ileal interposition duodenojejunal bypass
      operation on lipid metabolism in non-obese type 2 diabetes mellitus patients].
AB  - OBJECTIVE: To evaluate the effect of sleeve gastrectomy with ileal interposition
      duodenojejunal bypass operation on lipid metabolism in non-obese type 2 diabetes
      mellitus patients. METHODS: Twenty-nine non-obese patients with type 2 diabetes
      mellitus underwent sleeve gastrectomy with ileal interposition duodenojejunal
      bypass operation. All the patients were subjected to the measurement of total
      cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density
      lipoprotein (LDL), homeostatic model assessment for insulin resistance (Homa-IR),
      glycosylated hemoglobin (HbA1c) at postoperative 12th month. RESULTS: Twelve
      months after ileal interposition duodenojejunal bypass operation, the blood
      glucose was controlled without taking hypoglycemic drugs in 28 patients (96.5%)
      and HbA1c decreased from (8.4+/-1.3)% to (6.5+/-1.6)% (P<0.01). Dyslipidemia were
      corrected in 25 cases (86.2%). TC became normal in 84.2% (15/19), and TG became
      normal in 82.3% (14/17). HDL became normal in 66.6% (8/12). LDL became normal in
      31.2% (5/16). TC/HDL ratio decreased from 5.6+/-1.2 to 2.8+/-1.0 (P<0.01). TG/HDL
      ratio decreased from 3.2+/-1.3 to 1.5+/-0.8 (all P<0.01). CONCLUSION: Sleeve
      gastrectomy with ileal interposition duodenojejunal bypass is an effective
      operation for the correction of dyslipidemia in non-obese patients with type 2
      diabetes mellitus.

PMID- 23536352
TI  - [Clinical study of the predictors to neoadjuvant chemotherapy in patients with
      advanced gastric cancer].
AB  - OBJECTIVE: To investigate the predictive value of seven gastric cancer-associated
      factors on neoadjuvant chemotherapy in patients with advanced gastric cancer.
      METHODS: Expressions of C-met, EGFR, HER2, Ki-67, MMP7, P53 and TOPOII were
      detected by immunohistochemistry in gastric cancer tissues of 53 cases before and
      after mFOLFOX7 neoadjuvant chemotherapy. Chemotherapy efficacy was evaluated
      according to RECIST 1.1 standard combined with histopathology, and the
      relationship between various genes and chemotherapy efficacy was analyzed by
      univariate and logistic multivariate regression analyses. RESULTS: The clinical
      response rate was 52.8% (28/53) in neoadjuvant chemotherapy, including complete
      response in none, partial response in 28 cases (52.8%), stable disease in 24
      cases (45.3%) and progressive disease in 1 case (1.9%). The expressions of all
      the genes were not significantly different before and after neoadjuvant
      chemotherapy (P>0.05). Neoadjuvant chemotherapy efficacy was 83.3% (10/12) in the
      patients of HER2 positive expression and 43.9% (18/41) in the patients of HER2
      negative expression. The former was significant higher than the latter (P=0.016).
      Response rate of patients with P53 positive expression was 35.7% (10/28),
      significantly lower than 72.0% (18/25) of those with P53 negative expression
      (P=0.008). Six patients with both HER2 positive expression and P53 negative
      expression showed better efficacy. The expressions of C-met, EGFR, Ki-67, MMP7
      and TOPOII were not associated with response to neoadjuvant chemotherapy
      (P>0.05). HER2 and P53 were independent influencing factors of neoadjuvant
      chemotherapy (P<0.05). CONCLUSION: Expressions of HER2 and P53 have great value
      in the prediction of mFOLFOX7 neoadjuvant chemotherapy efficacy, suggesting that
      as independent factors, HER2 and P53 may be used to predict the efficacy before
      chemotherapy.

PMID- 23536353
TI  - [Molecular mechanism and therapeutic strategy for resistance to tyrosine kinase
      inhibitors in targeted treatment of gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of
      the GI tract. Aberrant activation of tyrosine kinase through mutated KIT or
      platelet-derived growth factor receptor (PDGFRA) is the key pathogenic factor in
      most cases. Tyrosine kinase inhibitors (TKI) such as imatinib and sunitinib can
      suppress activation of tyrosine kinase receptor and has gained wide recognition
      as the first-line adjuvant therapy for advanced or high-risk GIST after surgery.
      It has become the classic model of treatment for solid tumor with molecular
      targeted therapy. However, the emergence of drug-resistance limits the long-term
      benefit of these drugs in most patients and has been a challenging clinical
      concern. Many factors are related to the resistance of TKI, of which KIT/PDGFRA
      mutation is the most important one. Genetic amplification of KIT, loss of
      heterozygosity, activation of an alternative downstream signaling pathways, and
      drug concentration are all possible factors. Therefore, reasonable individual
      treatment strategy and early resistance evaluation for imatinib- and sunitinib
      resistant GISTs are important to patients with drug resistance in order to
      improve therapeutic efficacy and quality of life.

PMID- 23536354
TI  - [Treatment progress of gastrointestinal stromal tumor].
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the
      gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT
      and PDGFRalpha gene. Surgical resection is the only radical treatment at present,
      but recurrence is common. In recent years, targeted therapy with imatinib
      mesylate, which inhibits KIT kinase activity, represents the other cornerstone
      for the treatment of GIST. For resectable GIST, operation combined with
      neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase
      inhibitors can improve the prognosis of high-risk patients before or after
      complete resection. For unresectable GIST, targeted therapy with imatinib
      mesylate can effectively inhibit and ameliorate the progression of GIST.

PMID- 23536355
TI  - [Research progression in colorectal cancer stem cells].
AB  - Colorectal cancer (CRC) as a common malignancy in the digestive tract, its
      incidence and mortality increase significantly in China. Cancer stem cells (CSCs)
      are defined as a small fraction of tumor initiating cells that are endowed with
      both self-renewal and tumor growth potential. They may be responsible for tumor
      progression, metastasis, relapse and drug-resistance. Therefore, the isolation
      and characterization of tumorigenic CSCs in CRC may help to devise novel
      diagnostic and therapeutic procedures. This review briefly discusses the most
      recent advances in research on colorectal cancer stem cells including definition
      of the cancer stem cells, origin and specific markers of the colorectal CSCs.
      Transduction signal pathway involved in CSCs, potential therapeutic strategies
      targeting CSCs, and current issues in CSCs related research are also discussed.

PMID- 23536356
TI  - beta-synuclein aggregates and induces neurodegeneration in dopaminergic neurons.
AB  - OBJECTIVE: Whereas the contribution of alpha-synuclein to neurodegeneration in
      Parkinson disease is well accepted, the putative impact of its close homologue,
      beta-synuclein, is enigmatic. beta-Synuclein is widely expressed throughout the
      central nervous system, as is alpha-synuclein, but the physiological functions of
      both proteins remain unknown. Recent findings have supported the view that beta
      synuclein can act as an ameliorating regulator of alpha-synuclein-induced
      neurotoxicity, having neuroprotective rather than neurodegenerative capabilities,
      and being nonaggregating due to the absence of most of the aggregation-promoting
      NAC domain. However, a mutation of beta-synuclein linked to dementia with Lewy
      bodies rendered the protein neurotoxic in transgenic mice, and fibrillation of
      beta-synuclein has been demonstrated in vitro. METHODS: Neurotoxicity and
      aggregation properties of alpha-, beta-, and gamma-synuclein were comparatively
      elucidated in the rat nigro-striatal projection and in cultured neurons. RESULTS:
      Supporting the hypothesis that beta-synuclein can act as a neurodegeneration
      inducing factor, we demonstrated that wild-type beta-synuclein is neurotoxic for
      cultured primary neurons. Furthermore, beta-synuclein formed proteinase K
      resistant aggregates in dopaminergic neurons in vivo, leading to pronounced and
      progressive neurodegeneration in rats. Expression of beta-synuclein caused
      mitochondrial fragmentation, but this fragmentation did not render mitochondria
      nonfunctional in terms of ion handling and respiration even at late stages of
      neurodegeneration. A comparison of the neurodegenerative effects induced by alpha
      , beta-, and gamma-synuclein revealed that beta-synuclein was eventually as
      neurotoxic as alpha-synuclein for nigral dopaminergic neurons, whereas gamma
      synuclein proved to be nontoxic and had very low aggregation propensity.
      INTERPRETATION: Our results suggest that the role of beta-synuclein as a putative
      modulator of neuropathology in aggregopathies like Parkinson disease and dementia
      with Lewy bodies needs to be revisited.

PMID- 23536357
TI  - Mechanical allodynia in neuropathic pain. Where are the brain representations
      located? A positron emission tomography (PET) study.
AB  - BACKGROUND: Brain areas involved in nociception have been repeatedly
      investigated. Therefore, brain responses to physiological pain conditions are
      well identified. The same is not true for allodynic pain in patients with
      neuropathic pain since the cortical reorganizations that are involved in the
      conversion of non-noxious stimuli into painful sensations still remain unknown.
      METHODS: The present positron emission tomography (PET) study enrolled 19
      patients with dynamic mechanical allodynia to brushing or to cold rubbing of the
      skin. PET activations during allodynic stimulation were compared to those
      obtained with the same innocuous stimulation applied outside the neuropathic pain
      area (control). In a second comparison, they were compared with responses to a
      noxious heat stimulation applied outside the neuropathic pain area (experimental
      pain). RESULTS: Common responses to allodynia and control stimulations were found
      in contralateral SI, SII and insula and in ipsilateral cerebellum. Not
      surprisingly, heat pain condition was associated with activations in
      contralateral prefrontal and SII cortices and, bilaterally, in the anterior
      insular cortices. Distinctive cortical responses between control and allodynic
      conditions were restricted to one activation within the contralateral anterior
      insula, a region also activated by experimental heat pain. CONCLUSIONS: The
      insular subdivision was inappropriately activated considering the innocuous
      nature of the stimulus, but adequately activated with regard to pain-evoked
      sensation. Subcortically, the hypothesis of reorganization at any level of the
      somatosensory and pain pathways underlying such insular activity was supported by
      the observed shift of thalamic activation from a lateral-posterior to an anterior
      medial position.

PMID- 23536359
TI  - Early radial digital neuropathy of the thumb due to flexor pollicis longus
      tendinitis: value of ultrasound in an uncommon mild neuropathy.
AB  - INTRODUCTION: A 50-year-old man developed intermittent paresthesia of the outer
      portion of the right thumb. Paresthesia increased with thumb abduction and
      flexion. The remainder of the physical examination was normal. METHODS: Routine
      motor and sensory examinations of the median and ulnar nerves were within normal
      ranges. RESULTS: Ultrasonographic studies revealed that a tenosynovitis of the
      flexor pollicis longus of the right thumb was compressing the radial digital
      nerve of the thumb. CONCLUSIONS: Ultrasonographic evaluation was used in
      conjunction with nerve conduction studies to diagnose digital neuropathy.
      Ultrasound is a beneficial, complementary tool to electrodiagnostic studies,
      especially for uncommon focal neuropathies.

PMID- 23536358
TI  - Evaluation of atypical urine cytology progression to malignancy.
AB  - BACKGROUND: In urine cytology, the diagnosis of atypia is subjective and clinical
      management based on these results can be difficult to determine. In this study,
      the authors determined the percentage of atypical urine diagnoses that progressed
      to positive cytology or surgical pathology results over an 11-year period.
      METHODS: In a retrospective review of the authors' institution, 1320 atypical
      urine cytology diagnoses were identified in specimens from 851 patients obtained
      from January 2000 through December 2010. All subsequent pathology reports were
      reviewed to determine which patients developed positive cytology/surgical
      pathology diagnoses. In total, 4106 cytology and surgical pathology specimen
      reports were reviewed. RESULTS: At the authors' institution, 1320 of 16,299 of
      urine cytology specimens (8.1%) were diagnosed as atypical during the 11-year
      period. Overall, 271 of 1320 initial atypical urine specimens (21%) progressed to
      positive cytology or surgical pathology results with a mean time to progression
      of 155 days. Of the cases that progressed to malignancy, 118 were high-grade
      urothelial carcinoma and 92 were low-grade urothelial carcinoma. CONCLUSIONS: The
      rate of atypia in urine specimens at this institution was 8.1%. Of the specimen
      types, atypia was the most common in urinary diversion specimens (16%) and the
      least common in upper tract cytology (3.8%). When diagnosed as atypical, upper
      tract specimens had the highest percentage of progression to high-grade
      carcinoma. Therefore, the authors concluded that the diagnosis of atypia in this
      specimen group has higher clinical significance and should be managed more
      aggressively. Cancer (Cancer Cytopathol) 2013;121:387-391. (c) 2013 American
      Cancer Society.

PMID- 23536360
TI  - Hydrothermal treatment of naturally contaminated maize in the presence of sodium
      metabisulfite, methylamine and calcium hydroxide; effects on the concentration of
      zearalenone and deoxynivalenol.
AB  - Fusarium toxin-contaminated ground maize was hydrothermally treated in the
      presence of different combinations of chemicals in order to simultaneously reduce
      zearalenone (ZEA) and deoxynivalenol (DON) concentrations. Treatments were
      carried out in a laboratory conditioner at 80  degrees C and 17 % moisture. Six
      different treatments were performed, consisting of 3 doses of methylamine (MMA;
      2.5, 5 and 10 g/kg maize) at a constant dose of 5 g sodium metabisulfite
      (SBS)/kg, either with or without the addition of 20 g calcium hydroxide
      (Ca(OH)2)/kg. The used maize was contaminated with approximately 45.99 mg DON/kg
      and 3.46 mg ZEA/kg. Without the addition of Ca(OH)2, DON reductions reached
      approximately 82% after 1-min treatment and the toxin disappeared nearly
      completely after 10 min when 2.5 or 5 g MMA were applied. ZEA concentrations were
      only marginally affected. In the presence of Ca(OH)2, reductions in DON
      concentrations were lower, but were enhanced by increasing doses of MMA. ZEA
      concentrations were reduced by 72, 85 and 95% within the first 5 min of the
      treatment at MMA dosages of 2.5, 5 and 10 g/kg maize, respectively. The
      application of SBS in combination with a strong alkaline during hydrothermal
      treatment seems to be a promising approach to simultaneously decontaminate even
      high amounts of DON and ZEA in ground maize and may contribute to reduce the
      toxin load of diets.

PMID- 23536362
TI  - Pregnancy loss and later risk of atherosclerotic disease.
AB  - BACKGROUND: Pregnancy losses and atherosclerotic disease may be etiologically
      linked through underlying pathology. We examined whether miscarriage and
      stillbirth increase later risk of myocardial infarction, cerebral infarction, and
      renovascular hypertension. METHODS AND RESULTS: Among women pregnant at least
      once between 1977 and 2008, we identified a cohort of women with miscarriages,
      stillbirths, or live singleton births. These women were followed from the end of
      pregnancy for incident myocardial infarction, cerebral infarction, and
      renovascular hypertension. Using Poisson regression, we estimated incidence rate
      ratios for each of the outcomes by history of miscarriage and stillbirth. Among
      1,031,279 women followed for >15,928,900 person-years, we identified 27 98
      myocardial infarctions, 40 53 cerebral infarctions, and 1269 instances of
      renovascular hypertension. Women with stillbirths had 2.69 (95% confidence
      interval, 2.06-3.50), 1.74 (1.32-2.28), and 2.42 (1.59-3.69) times the rates of
      myocardial infarction, cerebral infarction, and renovascular hypertension,
      respectively, as women with no stillbirths. Compared with women with no
      miscarriages, women with miscarriages had 1.13 (1.03-1.24), 1.16 (1.07-1.25), and
      1.20 (1.05-1.38) times the rates of these same outcomes, respectively; these
      associations were dose dependent, with each additional miscarriage increasing the
      rates of myocardial and cerebral infarction and renovascular hypertension by 9%
      (3% to 16%), 13% (7% to 19%), and 19% (9% to 30%), respectively. Associations
      were strongest in younger women (<35 years). CONCLUSIONS: Pregnancy losses were
      associated with subsequent risks of myocardial infarction, cerebral infarction,
      and renovascular hypertension, consistent with either shared etiology or the
      initiation of pathological processes by a pregnancy loss leading to
      atherosclerosis.

PMID- 23536361
TI  - Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation
      of manganese superoxide dismutase via the SIRT1/FoxO3a pathway.
AB  - BACKGROUND: For reasons that remain unclear, whether type 5 adenylyl cyclase
      (AC5), 1 of 2 major AC isoforms in heart, is protective or deleterious in
      response to cardiac stress is controversial. To reconcile this controversy we
      examined the cardiomyopathy induced by chronic isoproterenol in AC5 transgenic
      (Tg) mice and the signaling mechanisms involved. METHODS AND RESULTS: Chronic
      isoproterenol increased oxidative stress and induced more severe cardiomyopathy
      in AC5 Tg, as left ventricular ejection fraction fell 1.9-fold more than wild
      type, along with greater left ventricular dilation and increased fibrosis,
      apoptosis, and hypertrophy. Oxidative stress induced by chronic isoproterenol,
      detected by 8-OhDG was 15% greater, P=0.007, in AC5 Tg hearts, whereas protein
      expression of manganese superoxide dismutase (MnSOD) was reduced by 38%,
      indicating that the susceptibility of AC5 Tg to cardiomyopathy may be
      attributable to decreased MnSOD expression. Consistent with this, susceptibility
      of the AC5 Tg to cardiomyopathy was suppressed by overexpression of MnSOD,
      whereas protection afforded by the AC5 knockout (KO) was lost in AC5 KO*MnSOD
      heterozyous KO mice. Elevation of MnSOD was eliminated by both sirtuin and MEK
      inhibitors, suggesting both the SIRT1/FoxO3a and MEK/ERK pathway are involved in
      MnSOD regulation by AC5. CONCLUSIONS: Overexpression of AC5 exacerbates the
      cardiomyopathy induced by chronic catecholamine stress by altering regulation of
      SIRT1/FoxO3a, MEK/ERK, and MnSOD, resulting in oxidative stress intolerance,
      thereby shedding light on new approaches for treatment of heart failure.

PMID- 23536364
TI  - Iron metal-organic frameworks MIL-88B and NH2-MIL-88B for the loading and
      delivery of the gasotransmitter carbon monoxide.
AB  - Crystals of MIL-88B-Fe and NH2-MIL-88B-Fe were prepared by a new rapid microwave
      assisted solvothermal method. High-purity, spindle-shaped crystals of MIL-88B-Fe
      with a length of about 2 MUm and a diameter of 1 MUm and needle-shaped crystals
      of NH2-MIL-88B-Fe with a length of about 1.5 MUm and a diameter of 300 nm were
      produced with uniform size and excellent crystallinity. The possibility to reduce
      the as-prepared frameworks and the chemical capture of carbon monoxide in these
      materials was studied by in situ ultrahigh vacuum Fourier-transform infrared (UHV
      FTIR) spectroscopy and Mossbauer spectroscopy. CO binding occurs to unsaturated
      coordination sites (CUS). The release of CO from the as-prepared materials was
      studied by a myoglobin assay in physiological buffer. The release of CO from
      crystals of MIL-88B-Fe with t(1/2) = 38 min and from crystals of NH2-MIL-88B-Fe
      with t(1/2) = 76 min were found to be controlled by the degradation of the MIL
      materials under physiological conditions. These MIL-88B-Fe and NH2-MIL-88B-Fe
      materials show good biocompatibility and have the potential to be used in
      pharmacological and therapeutic applications as carriers and delivery vehicles
      for the gasotransmitter carbon monoxide.

PMID- 23536363
TI  - Cutaneous alpha, beta and gamma human papillomaviruses in relation to squamous
      cell carcinoma of the skin: a population-based study.
AB  - Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient
      populations, may contribute to the pathogenesis of keratinocyte cancers,
      particularly squamous cell carcinomas (SCC). However, their role in SCC in the
      general population is less clear. We conducted a comprehensive analysis to
      investigate the independent effects of seropositivity for cutaneous alpha, beta
      and gamma HPV types on risk of SCC, and a meta-analysis of the available
      literature. In a population-based case-control study from New Hampshire, USA (n =
      1,408), histologically confirmed SCC cases and controls were tested for L1
      antibodies to alpha, beta and gamma cutaneous HPV types 2-5, 7-10, 15, 17, 20,
      23, 24, 27b, 36, 38, 48-50, 57, 65, 75-77, 88, 92, 95, 96, 101, 103 and 107 using
      multiplex serology. An increasing risk of SCC with number of beta HPVs to which
      an individual tested positive was observed even among those seronegative for
      gamma types (p for trend = 0.016) with an odds ratio of 1.95 (95% confidence
      interval (CI) = 1.07-3.56) for four or more beta types positive. In a meta
      analysis of six case-control studies, increased SCC risks in relation to beta HPV
      seropositivity were found across studies (meta odds ratio = 1.45, CI = 1.27
      1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC
      cases than controls, the association was only weakly evident among those
      seronegative for beta HPVs. Overall, the association between cutaneous HPVs and
      skin cancers appears to be specific to SCC and to genus beta HPVs in a general US
      population. 

PMID- 23536366
TI  - An ethical approach to dialysis--an alliance of nephrology, palliative medicine
      and ethics.

PMID- 23536365
TI  - Fibrohistiocytoma: a rare tumour of the trachea.

PMID- 23536367
TI  - The prevalence of diabetes, pre-diabetes and the metabolic syndrome in an Irish
      regional homeless population.
AB  - BACKGROUND: Diabetes is a major chronic health condition. Prevalence is rising,
      superseding public health estimates. Chronic diseases are more common among lower
      socioeconomic groups, for example, the homeless population. There is paucity of
      data on the health status of the homeless population in Ireland, and the
      prevalence of diabetes and associated cardiovascular risk factors is unknown.
      AIM: We aimed to assess the prevalence of diabetes, pre-diabetes and the
      metabolic syndrome (MetS) in an Irish regional homeless population. DESIGN: This
      study is a cross-sectional study of the homeless population living in a regional
      university city of Ireland. METHODS: After informed consent and following an
      overnight fast, blood was drawn for fasting plasma glucose, total cholesterol,
      triglycerides, high-density lipoprotein, low-density lipoprotein and glycosylated
      haemoglobin (HbA1c). A 75 g glucose load was given orally and an oral glucose
      tolerance test completed. Anthropometric measurements and blood pressure were
      recorded. Smoking, alcohol and drug status were noted. RESULTS: Of the 252
      participants, 8% (n = 20), 10% (n = 24) and 21% (n = 54) were diagnosed with type
      2 diabetes, pre-diabetes and MetS, respectively. Obesity (body mass index >30)
      was present in 22%, while 90% displayed abdominal obesity. Participants who
      screened positive for diabetes, pre-diabetes and MetS demonstrated an inferior
      cardiovascular risk profile. CONCLUSION: The prevalence of diabetes, pre-diabetes
      and MetS in this homeless population is in keeping with national estimates. As
      this cohort is less likely to seek health care, this may result in later
      diagnosis and a greater risk of diabetic complications at presentation.

PMID- 23536369
TI  - Three testis-specific paralogous serine proteases play different roles in murine
      spermatogenesis and are involved in germ cell survival during meiosis.
AB  - Spermatogenesis is a complex process that generates spermatozoa; its molecular
      mechanisms are not completely understood. Here we focused on the functions of
      three testis-specific serine proteases: Prss42/Tessp-2, Prss43/Tessp-3, and
      Prss44/Tessp-4. These protease genes, which constitute a gene cluster on
      chromosome 9F2-F3, were presumed to be paralogs and were expressed only in the
      testis. By investigating their mRNA distribution, we found that all three genes
      were expressed in primary and secondary spermatocytes. However, interestingly,
      the translated proteins were produced at different locations. Prss42/Tessp-2 was
      found in the membranes and cytoplasm of secondary spermatocytes and spermatids,
      whereas Prss43/Tessp-3 was present only in the membranes of spermatocytes and
      spermatids. Prss44/Tessp-4 was detected in the cytoplasm of spermatocytes and
      spermatids. To assess the roles of these proteases in spermatogenesis, we used
      organ culture of mouse testis fragments. Adding antibodies against Prss42/Tessp-2
      and Prss43/Tessp-3 resulted in meiotic arrest at the stage when each protease was
      beginning to be translated. Furthermore, the number of apoptotic cells
      dramatically increased after the addition of these antibodies. These results
      strongly suggest that the three paralogous Prss/Tessp proteases play different
      roles in spermatogenesis and that Prss42/Tessp-2 and Prss43/Tessp-3 are required
      for germ cell survival during meiosis.

PMID- 23536368
TI  - Regulated expression of Rhox8 in the mouse ovary: evidence for the role of
      progesterone and RHOX5 in granulosa cells.
AB  - The gonadotropin surge is the essential trigger to stimulate ovulation and
      luteinization of ovarian follicles. While the hormone signals from the brain that
      initiate ovulation are known, the specific targets which regulate this process
      are not well known. In this study, we assessed the suitability of the Rhox
      homeobox gene cluster to serve as the master regulators of folliculogenesis. In
      superovulated (equine chorionic gonadotropin [eCG]/human chorionic gonadotropin
      [hCG]) mice, the Rhox genes exhibited four distinct windows of peak expression,
      suggesting that these genes may regulate specific events during the ovulatory
      cycle. Like many members of the cluster, Rhox8 mRNA and protein were induced by
      follicle stimulating hormone [FSH]/eCG in granulosa cells. However, Rhox8
      displayed unique peak expression at 8 h post-hCG administration, implying it
      might be the lone member of the cluster regulated by progesterone. Subsequent
      promoter analysis in granulosa cells revealed relevant homeobox binding and
      progesterone response elements within Rhox8's 5'-flanking region. In
      superovulated mice, progesterone receptor (PGR) is recruited to the Rhox8
      promoter, as assessed by chromatin immunoprecipitation. In Rhox5-null mice, Rhox8
      mRNA was reduced at 2 h and 4 h post-hCG administration but recovered once the
      follicles passed the antral stage of development. Conversely, in progesterone
      receptor knockout mice, Rhox8 exhibited normal stimulation by eCG but failed to
      reach its peak mRNA level at 8 h post-hCG found in wild-type mice. This suggests
      a model in which Rhox8 transcription is dependent upon RHOX5 during early
      folliculogenesis and upon progesterone during the periovulatory window when RHOX5
      normally wanes. In support of this model, transfection of RHOX5 and PGR
      expression plasmids stimulated, whereas dominant negative and mutant constructs
      inhibited, Rhox8 promoter activity.

PMID- 23536370
TI  - Mechanisms of angiogenic suppression in uteri exposed to diethylstilbestrol
      neonatally in the mouse.
AB  - Perinatal estrogen exposure elicits a wide range of abnormalities in the female
      genital tract. Since angiogenesis is essential for morphogenesis, we investigated
      the vascular density, integrity of vasculatures, and expression of angiogenic
      factors and their receptors in the uteri of mice treated with diethylstilbestrol
      (DES) neonatally (DES-mice); the uteri were collected from Day 4 to Day 20. DES
      treatment reduced the number and density of vasculatures immunostained with
      PECAM1 (platelet and endothelial cell adhesion molecule 1) in the stroma.
      Horseradish peroxidase injected into the left ventricle leaked into the
      endometrium and myometrium on Day 10 in the DES-mice but not in the controls.
      Electron microscopy confirmed the immaturity of the capillaries, which had an
      incomplete basal lamina and fewer pericytes. Immunohistochemical studies
      demonstrated that VEGFA (vascular endothelial growth factor A) expression and
      ANGPT1 (angiopoietin 1) expression were down-regulated in the stromal cells until
      Days 20 and 10, respectively. The number of vasculatures with ANGPT2
      immunoreaction was reduced in the DES-mice. DES treatment suppressed the
      expression of VEGFR2 (VEGF receptor 2) and the co-receptor NRP1 (neuropilin 1) as
      well as TEI2 in the vasculatures. The results of RT-PCR and Western blotting
      supported the down-regulation of the expression of angiogenic factors and their
      receptors in DES-mice, whereas the VEGFR1 protein expression was up-regulated.
      These results suggested that the low concentration of angiogenic factors in the
      stroma was primarily responsible for the low vascular density in the stroma of
      the DES-mice, and that the low vascular density and immature vasculatures
      resulted in uterine malformations.

PMID- 23536371
TI  - Computer simulation of the rodent spermatogonial stem cell niche.
AB  - A computer program has been developed that simulates the behavior of
      spermatogonial stem cells (SSCs) and their offspring inside and outside of the
      stem cell niche. Various parameters derived from previous morphological and cell
      kinetic studies have been used to set up an Excel-based computer program that
      simulates the proliferative activity of SSCs during the seminiferous epithelial
      cycle. SSCs and their offspring are depicted in a virtual piece of seminiferous
      tubule in which the daughter cells of self-renewing divisions of SSCs migrate
      away from each other, while after SSC differentiation a pair of cells is formed.
      Those SSC daughter cells that migrate out of the niche will very likely
      differentiate at their next division. Putting in physiologically acceptable
      parameters, the program renders numbers of spermatogonial cell types similar to
      those previously counted in whole mounts of seminiferous tubules. In this model,
      SSC numbers and numbers of differentiating cells remain constant for more than 50
      virtual epithelial cycles, i.e., more than 1 yr of a mouse life and 2 yr of that
      of a Chinese hamster. The program can simulate various recent cell kinetic
      experiments and confirms, or offers alternative explanations for, the results
      obtained, showing its usefulness in spermatogenesis research.

PMID- 23536372
TI  - Comparative importance of fatty acid beta-oxidation to nuclear maturation, gene
      expression, and glucose metabolism in mouse, bovine, and porcine cumulus oocyte
      complexes.
AB  - The objective of these experiments was to evaluate the importance of fatty acid
      beta-oxidation (FAO) in the cumulus oocyte complex (COC) during in vitro
      maturation (IVM) to oocyte nuclear maturation and gene expression in both the
      oocyte and cumulus cells in three species with differing amounts of oocyte
      intracellular lipids (mouse, low; bovine, moderate; porcine, high). We inhibited
      FAO using etomoxir at 0, 10, 25, 100, or 250 MUM. Completion of oocyte nuclear
      maturation was inhibited after COC exposure to 250 MUM etomoxir in mouse oocytes,
      100 MUM etomoxir in bovine oocytes, and as little as 10 MUM etomoxir in porcine
      oocytes (P < 0.05). When FAO was inhibited in mouse and porcine COCs resulting in
      inhibition of meiosis, the abundance of FAO, glycolytic, and oxidative stress
      gene transcripts were decreased in oocytes and cumulus cells (P < 0.05), although
      to a much greater extent in the pig. In bovine oocytes and cumulus cells, FAO
      gene transcripts were increased and glycolytic gene expression altered following
      meiotic inhibition due to etomoxir. Etomoxir, at doses that did not inhibit
      nuclear maturation in bovine and murine COCs, increased glucose consumption (P <
      0.05), suggesting glucose metabolism is increased to meet the metabolic demands
      of the COCs when fatty acid metabolism is compromised. Our data demonstrates that
      FAO is essential to oocyte nuclear maturation in all three species. Sensitivity
      of nuclear maturation to FAO inhibition reflects the amount of lipid present in
      the ooplasm and may suggest a relative reliance on this metabolic pathway.

PMID- 23536374
TI  - Efficient embryo transfer in the common marmoset monkey (Callithrix jacchus) with
      a reduced transfer volume: a non-surgical approach with cryopreserved late-stage
      embryos.
AB  - Among primates, the common marmoset is suitable for primate embryology research.
      Its small body size, however, has delayed the technical development of efficient
      embryo transfer. Furthermore, three factors have been determined to adversely
      affect the performance of marmoset embryo transfer: nonsurgical approaches, the
      use of cryopreserved embryos, and the use of late-stage embryos. Here we
      performed embryo transfer under conditions that included the above three factors
      and using either a small (1 MUl or less) or a large volume (2-3 MUl) of medium.
      The pregnancy and birth rates were 50% (5/10) and 27% (3/11), respectively, when
      using the large volume, and 80% (8/10) and 75% (9/12), respectively, when using
      the small volume. The latter scores exceed those of previous reports using
      comparable conditions. Thus, it appears that these three previously considered
      factors could be overcome, and we propose that reducing the transfer volume to 1
      MUl or less is essential for successful marmoset embryo transfer.

PMID- 23536373
TI  - Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell
      associations and spermatogonial stem cells in mice.
AB  - Recent evidence has linked human phthalate exposure to abnormal reproductive and
      hormonal effects. Phthalates are plasticizers that confer flexibility and
      transparency to plastics, but they readily contaminate the body and the
      environment. In this study, timed pregnant CD1 outbred mice were treated with di
      (2-ethylhexyl) phthalate (DEHP) from Embryonic Day 7 (E7) to E14. The subsequent
      generation (F1) offspring were then bred to produce the F2, F3, and F4 offspring,
      without any further DEHP treatment. This exposure scheme disrupted testicular
      germ cell association and decreased sperm count and motility in F1 to F4
      offspring. By spermatogonial transplantation techniques, the exposure scheme also
      disrupted spermatogonial stem cell (SSC) function of F3 offspring. The W/W(V)
      recipient testes transplanted with F3 offspring germ cells from the DEHP-treated
      group had a dramatically lower percentage of donor germ cell-derived
      spermatogenic recovery in seminiferous tubules when compared to the recipient
      testes transplanted with CD1 control germ cells. Further characterization showed
      that the major block of donor germ cell-derived spermatogenesis was before the
      appearance of undifferentiated spermatogonia. Interestingly, the testes
      transplanted with the F3 offspring germ cells from the DEHP-treated group, when
      regenerated, replicated testis morphology similar to that observed in the testes
      from the F1 to F3 offspring of the DEHP-treated group, suggesting that the germ
      cell disorganization phenotype originates from the stem cells of F3 offspring. In
      conclusion, embryonic exposure to DEHP was found to disrupt testicular germ cell
      organization and SSC function in a transgenerational manner.

PMID- 23536375
TI  - Transcriptional and functional adaptations of human endothelial cells to
      physiological chronic low oxygen.
AB  - Endothelial cells chronically reside in low-O2 environments in vivo (2%-13% O2),
      which are believed to be critical for cell homeostasis. To elucidate the roles of
      this physiological chronic normoxia in human endothelial cells, we examined
      transcriptomes of human umbilical vein endothelial cells (HUVECs), proliferation
      and migration of HUVECs in response to fibroblast growth factor 2 (FGF2) and
      vascular endothelial growth factor A (VEGFA), and underlying signaling mechanisms
      under physiological chronic normoxia. Immediately after isolation, HUVECs were
      cultured steadily under standard cell culture normoxia (SCN; 21% O2) or
      physiological chronic normoxia (PCN; 3% O2) up to 25 days. We found that PCN up
      regulated 41 genes and down-regulated 21 genes, 90% of which differed from those
      previously reported from HUVECs cultured under SCN and exposed to acute low O2.
      Gene ontology analysis indicated that PCN-regulated genes were highly related to
      cell proliferation and migration, consistent with the results from benchtop
      assays that showed that PCN significantly enhanced FGF2- and VEGFA-stimulated
      cell proliferation and migration. Interestingly, preexposing the PCN cells to 21%
      O2 up to 5 days did not completely diminish PCN-enhanced cell proliferation and
      migration. These PCN-enhanced cell proliferations and migrations were mediated
      via augmented activation of MEK1/MEK2/ERK1/ERK2 and/or PI3K/AKT1. Importantly,
      these PCN-enhanced cellular responses were associated with an increase in
      activation of VEGFR2 but not FGFR1, without altering their expression. Thus, PCN
      programs endothelial cells to undergo dramatic changes in transcriptomes and
      sensitizes cellular proliferative and migratory responses to FGF2 and VEGFA.
      These PCN cells may offer a unique endothelial model, more closely mimicking the
      in vivo states.

PMID- 23536376
TI  - Heptametallic, octupolar nonlinear optical chromophores with six ferrocenyl
      substituents.
AB  - New complexes with six ferrocenyl (Fc) groups connected to Zn(II) or Cd(II)
      tris(2,2'-bipyridyl) cores are described. A thorough characterisation of their
      BPh4(-) salts includes two single-crystal X-ray structures, highly unusual for
      such species with multiple, extended substituents. Intense, visible d(Fe(II))
      >pi* metal-to-ligand charge-transfer (MLCT) bands accompany the pi->pi*
      intraligand charge-transfer absorptions in the near UV region. Each complex shows
      a single, fully reversible Fe(III/II) wave when probed electrochemically.
      Molecular quadratic nonlinear optical (NLO) responses are determined by using
      hyper-Rayleigh scattering and Stark spectroscopy. The latter gives static first
      hyperpolarisabilities beta0 reaching as high as approximately 10(-27)  esu and
      generally increasing with pi-conjugation extension. Z-scan cubic NLO measurements
      reveal high two-photon absorption cross-sections sigma2 of up to 5400 GM in one
      case. DFT calculations reproduce the pi-conjugation dependence of beta0, and TD
      DFT predicts three transitions close in energy contributing to the MLCT bands.
      The lowest energy transition has octupolar character, whereas the other two are
      degenerate and dipolar in nature.

PMID- 23536378
TI  - Landscape influences on climate-related lake shrinkage at high latitudes.
AB  - Climate-related declines in lake area have been identified across circumpolar
      regions and have been characterized by substantial spatial heterogeneity. An
      improved understanding of the mechanisms underlying lake area trends is necessary
      to predict where change is most likely to occur and to identify implications for
      high latitude reservoirs of carbon. Here, using a population of ca. 2300 lakes
      with statistically significant increasing and decreasing lake area trends
      spanning longitudinal and latitudinal gradients of ca. 1000 km in Alaska, we
      present evidence for a mechanism of lake area decline that involves the loss of
      surface water to groundwater systems. We show that lakes with significant
      declines in lake area were more likely to be located: (1) in burned areas; (2) on
      coarser, well-drained soils; and (3) farther from rivers compared to lakes that
      were increasing. These results indicate that postfire processes such as
      permafrost degradation, which also results from a warming climate, may promote
      lake drainage, particularly in coarse-textured soils and farther from rivers
      where overland flooding is less likely and downslope flow paths and negative
      hydraulic gradients between surface water and groundwater systems are more
      common. Movement of surface water to groundwater systems may lead to a deepening
      of subsurface flow paths and longer hydraulic residence time which has been
      linked to increased soil respiration and CO2 release to the atmosphere. By
      quantifying relationships between statewide coarse resolution maps of landscape
      characteristics and spatially heterogeneous responses of lakes to environmental
      change, we provide a means to identify at-risk lakes and landscapes and plan for
      a changing climate.

PMID- 23536379
TI  - Subclinical rhythmic electroencephalogram discharge of adults occurring during
      sleep: a diagnostic challenge.
AB  - Subclinical rhythmic electroencephalogram discharge of adults (SREDA) is an
      electroencephalogram (EEG) pattern of uncertain significance, which occurs
      without any correlation with epilepsy. It resembles epileptiform activity, and is
      therefore likely to be misinterpreted as an authentic epileptiform pattern. We
      describe the occurrence of SREDA during stage II nonrapid eye movement (NREM)
      sleep and discuss the diagnostic difficulties that may arise when such a pattern
      is encountered during sleep EEG recordings. SREDA may occur during sleep, leading
      to difficulties in correct identification of this pattern, as the patient is
      unconscious and unable to report any symptoms. Although there are rather
      distinctive EEG features, the lack of changes in electrocardiogram rhythm and the
      absence of ocular/muscular artifacts suggest a nonepileptic phenomenon. The
      ultimate diagnosis, and the correct identification of SREDA, may be achieved by a
      comparison of EEG features between the pattern occurring during sleep and that
      recorded in the awake state. 

PMID- 23536377
TI  - Leptomeningeal collaterals are associated with modifiable metabolic risk factors.
AB  - OBJECTIVE: We sought to identify potentially modifiable determinants associated
      with variability in leptomeningeal collateral status in patients with acute
      ischemic stroke. METHODS: Data are from the Keimyung Stroke Registry. Consecutive
      patients with M1 segment middle cerebral artery +/- intracranial internal carotid
      artery occlusions on baseline computed tomographic angiography (CTA) from May
      2004 to July 2009 were included. Baseline and follow-up imaging was analyzed
      blinded to all clinical information. Two raters assessed leptomeningeal
      collaterals on baseline CTA by consensus, using a previously validated regional
      leptomeningeal score (rLMC). RESULTS: Baseline characteristics (N = 206) were:
      mean age = 66.9 +/- 11.6 years, median baseline National Institutes of Health
      Stroke Scale = 14 (interquartile range [IQR] = 11-20), and median time from
      stroke symptom onset to CTA = 166 minutes (IQR = 96-262). Poor collateral status
      at baseline (rLMC score = 0-10) was seen in 73 of 206 patients (35.4%). On
      univariate analyses, patients with poor collateral status at baseline were older;
      were hypertensive; had higher white blood cell count, blood glucose, D-dimer, and
      serum uric acid levels; and were more likely to have metabolic syndrome.
      Multivariate modeling identified metabolic syndrome (odds ratio [OR] = 3.22, 95%
      confidence interval [CI] = 1.69-6.15, p < 0.001), hyperuricemia (per 1mg/dl serum
      uric acid; OR = 1.35, 95% CI = 1.12-1.62, p < 0.01), and older age (per 10 years;
      OR = 1.34, 95% CI = 1.02-1.77, p = 0.03) as independent predictors of poor
      leptomeningeal collateral status at baseline. INTERPRETATION: Metabolic syndrome,
      hyperuricemia, and age are associated with poor leptomeningeal collateral status
      in patients with acute ischemic stroke.

PMID- 23536380
TI  - Clinical advantages of quantitative electroencephalogram (QEEG)-electrical
      neuroimaging application in general neurology practice.
AB  - QEEG-electrical neuroimaging has been underutilized in general neurology practice
      for uncertain reasons. Recent advances in computer technology have made this
      electrophysiological testing relatively inexpensive. Therefore, this study was
      conducted to evaluate the clinical usefulness of QEEG/electrical neuroimaging in
      neurological practice. Over the period of approximately 6 months, 100 consecutive
      QEEG recordings were analyzed for potential clinical benefits. The patients who
      completed QEEG were divided into 5 groups based on their initial clinical
      presentation. The main groups included patients with seizures, headaches, post
      concussion syndrome, cognitive problems, and behavioral dysfunctions.
      Subsequently, cases were reviewed and a decision was made as to whether QEEG
      analysis contributed to the diagnosis and/or furthered patient's treatment.
      Selected and representative cases from each group are presented in more detail,
      including electrical neuroimaging with additional low-resolution electromagnetic
      tomography analysis or using computerized cognitive testing. Statistical analysis
      showed that QEEG analysis contributed to 95% of neurological cases, which
      indicates great potential for wider application of this modality in general
      neurology. Many patients also began neurotherapy, depending on the patient's
      desire to be involved in this treatment modality. 

PMID- 23536381
TI  - Embedded grey relation theory in Hopfield neural network: application to motor
      imagery EEG recognition.
AB  - In this study, grey-based Hopfield neural network (GHNN), is proposed for the
      unsupervised analysis of motor imagery (MI) electroencephalogram (EEG) data.
      Combined with segment selection and feature extraction, GHNN is used for the
      recognition of left and right MI data. A Gaussian-like filter is proposed to
      reduce noise, to further enhance performance of active segment selection.
      Features are extracted by coherence from wavelet data, and then discriminated by
      GHNN, which is an unsupervised approach suitable for the online classification of
      nonstationary biomedical signals. Compared to EEG data without segment selection,
      several usual features, and classifiers, the proposed system is potentially an
      analytic approach in brain-computer interface (BCI) applications. 

PMID- 23536382
TI  - Neurofeedback training induces changes in white and gray matter.
AB  - The main objective of this structural magnetic resonance imaging (MRI) study was
      to investigate, using diffusion tensor imaging, whether a neurofeedback training
      (NFT) protocol designed to improve sustained attention might induce structural
      changes in white matter (WM) pathways, purportedly implicated in this cognitive
      ability. Another goal was to examine whether gray matter (GM) volume (GMV) might
      be altered following NFT in frontal and parietal cortical areas connected by
      these WM fiber pathways. Healthy university students were randomly assigned to an
      experimental group (EXP), a sham group, or a control group. Participants in the
      EXP group were trained to enhance the amplitude of their beta1 waves at F4 and
      P4. Measures of attentional performance and MRI data were acquired one week
      before (Time 1) and one week after (Time 2) NFT. Higher scores on visual and
      auditory sustained attention were noted in the EXP group at Time 2 (relative to
      Time 1). As for structural MRI data, increased fractional anisotropy was measured
      in WM pathways implicated in sustained attention, and GMV increases were detected
      in cerebral structures involved in this type of attention. After 50 years of
      research in the field of neurofeedback, our study constitutes the first empirical
      demonstration that NFT can lead to microstructural changes in white and gray
      matter. 

PMID- 23536383
TI  - Tongue somatosensory-evoked potentials: evaluation of the afferent trigeminal
      pathway in patients with early multiple sclerosis.
AB  - The aim of this study was to determine the efficacy of tongue somatosensory
      evoked potentials (tSSEPs) in evaluation of afferent trigeminal pathway in
      patients with early multiple sclerosis (MS). The tSSEP was performed on 10
      healthy volunteers and 10 patients with the first symptom of MS. Data were
      compared between the groups, and tSSEP findings of patients with MS were
      correlated with clinical and magnetic resonance imaging (MRI) data. Among 10
      patients, 2 (20%) had clinically evident involvement of the brainstem, 5 (50%)
      had brainstem lesions on brain MRI, while 9 (90%) had prolonged latencies on
      tSSEP. Of the 8 patients with no clinical evidence of brainstem pathology, 7
      (88%) had prolonged latencies/conduction block on tSSEP. Patients had
      statistically significant prolongation of N1, P1, and N2 latencies for
      stimulation of the right side and N2 latency for stimulation of the left side
      compared to healthy controls. The tSSEP is an efficient method for evaluating the
      afferent trigeminal pathway in patients with early MS. This study provides
      evidence that lesions of the afferent trigeminal pathway are more frequently
      found by tSSEP than by clinical examination or MRI. 

PMID- 23536384
TI  - The use of stained cytologic direct smears for ALK gene rearrangement analysis of
      lung adenocarcinoma.
AB  - BACKGROUND: Rearrangements involving the anaplastic lymphoma kinase (ALK) gene
      are present in approximately 5% of lung adenocarcinomas. Crizotinib is approved
      for the treatment of lung adenocarcinomas harboring ALK rearrangements. Patients
      with advanced stage lung cancer are not candidates for surgical resection of
      their primary tumors. For these patients, cytologic specimens often represent the
      only diagnostic tissue available. Cell blocks (CBs) are routinely used for
      molecular studies; however, insufficient CB cellularity can impede the
      performance of these assays. METHODS: Thirty-two cytology cases of lung
      adenocarcinomas were analyzed by fluorescence in situ hybridization (FISH) for
      ALK rearrangements. Diff-Quik-stained smears were examined to identify tumor cell
      enriched areas that were marked using a diamond-tipped scribe. Paired ALK
      rearrangement FISH was performed using smears and CBs in each case. RESULTS: An
      ALK rearrangement was detected on direct smears and CB sections in 5 (16%) and 4
      (13%), respectively, of the 32 cases studied. Concordant FISH results for smears
      and CBs were observed in 31 (97%) of 32 cases. In the 1 discordant case, an ALK
      rearrangement was detected on the direct smear but not in the CB. Reverse
      transcriptase-polymerase chain reaction analysis of this CB revealed the presence
      of an EML4-ALK rearrangement, thereby confirming a false-negative FISH result in
      the CB. CONCLUSIONS: Stained cytologic direct smears can be effectively used for
      ALK rearrangement analysis by FISH. This approach represents a useful safeguard
      when insufficient CB cellularity is encountered and could prevent delays in
      treatment in this era of precision medicine.

PMID- 23536385
TI  - ANNA-1 (anti-Hu) associated sensory neuronopathy with malignant mixed mullerian
      tumor.

PMID- 23536386
TI  - Cerebrovascular autoregulation in critically ill patients during continuous
      hemodialysis.
AB  - PURPOSE: In chronic renal failure, intermittent hemodialysis decreases cerebral
      blood flow velocity (CBFV); however, in critically ill patients with acute renal
      failure, the effect of continuous venovenous hemodialysis (CVVHD) on CBFV and
      cerebrovascular autoregulation (AR) is unknown. Therefore, a study was undertaken
      to investigate the potential effect of CVVHD on CBFV and AR in patients with
      acute renal failure. METHODS: This cohort study investigated 20 patients with
      acute renal failure who required CVVHD. In these patients, the CBFV and index of
      AR (Mx) were measured using transcranial Doppler before and during CVVHD.
      RESULTS: The median Mx values at baseline were 0.33 [interquartile range (IQR):
      0.02-0.55], and during CVVHD, they were 0.20 [0.07-0.40]. The differences in Mx
      (CVVHD--baseline) was (median [IQR]) -0.015 [-0.19-0.05], 95% confidence interval
      (CI) -0.16 to 0.05. The Mx was > 0.3 in 11/20 patients at baseline measurement.
      Six of these patients recovered to Mx < 0.3 during CVVHD. The CBFV was (median
      [IQR]) 47 [36-59] cm . sec(-1) at baseline and 49 [36-66] cm . sec(-1) during
      CVVHD. The difference of CBFV was 0.0 [-4 - 2.7], 95% CI -2.5 to 4.2. CONCLUSION:
      Compared with patients with intermittent hemodialysis, CVVHD did not influence
      CBFV and AR in critically ill patients with acute renal failure, possibly due to
      lower extracorporeal blood flow, slower change of plasma osmolarity, and a lower
      fluid extraction rate. In a subgroup of patients with sepsis, the AR was impaired
      at baseline in more than half of the patients, and this was reversed during
      CVVHD. The trial was registered at ClinicalTrials.gov ID: NCT01376531.

PMID- 23536387
TI  - Competence.

PMID- 23536388
TI  - Endolymphatic hydrops and cerebrospinal fluid pressure: a 30-year update.

PMID- 23536389
TI  - Response to comments in "endolymphatic hydrops and cerebrospinal fluid pressure,"
      by anthony gordon.

PMID- 23536390
TI  - The mortality observed-to-expected ratio in otolaryngology.

PMID- 23536391
TI  - Response to: "The mortality observed-to-expected ratio in otolaryngology," from
      Roberson.

PMID- 23536393
TI  - The involvement of the RET variant G691S in medullary thyroid carcinoma:
      conflicting results of meta-analyses need to be reconciled.

PMID- 23536394
TI  - Carbodeoxygenation of biomass: the carbonylation of glycerol and higher polyols
      to monocarboxylic acids.
AB  - Glycerol is converted to a mixture of butyric and isobutyric acid by rhodium- or
      iridium-catalysed carbonylation using HI as the co-catalyst. The initial reaction
      of glycerol with HI results in several intermediates that lead to isopropyl
      iodide, which upon carbonylation forms butyric and isobutyric acid. At low HI
      concentration, the intermediate allyl iodide undergoes carbonylation to give
      vinyl acetic acid and crotonic acid. Higher polyols C(n)H(n+2)(OH)(n) are
      carbonylated to the corresponding C(n+1) mono-carboxylic acids.

PMID- 23536395
TI  - [A needs-oriented discharge planning intervention for high utilisers of
      psychiatric services: quality of the implementation and opportunities for
      improvement].
AB  - OBJECTIVE: Process evaluation of a needs-oriented discharge planning and
      monitoring (NODPAM) intervention for patients with severe mental illness with
      high utilisation of inpatient psychiatric care (within a RCT showing lack of
      evidence of superiority over treatment as usual). METHODS: Analysis of
      intervention drop-outs vs. intervention group patients participating in the
      intervention; analysis of the impact of intervention characteristics on unmet
      needs over time. RESULTS: Patients with more severe forms of illness were more
      likely to be among intervention drop-outs, a relatively high proportion of unmet
      needs persisted in patients participating in the intervention. Good intervention
      implementation and high patient satisfaction with the intervention were
      associated with a reduction of unmet needs. CONCLUSIONS: The NODPAM intervention
      failed to reach patients with high service use and more severe forms of illness;
      quality of intervention implementation might have contributed to the lack of
      superiority over treatment as usual. The intervention might not have been well
      integrated in routine treatment and was therefore experienced as extraneous to
      routine care.

PMID- 23536396
TI  - Comparing positron emission tomography imaging and cerebrospinal fluid
      measurements of beta-amyloid.
AB  - OBJECTIVE: We examined agreement and disagreement between 2 biomarkers of beta
      amyloid (Abeta) deposition (amyloid positron emission tomography [PET] and
      cerebrospinal fluid [CSF] Abeta1-42 ) in normal aging and dementia in a large
      multicenter study. METHODS: Concurrently acquired florbetapir PET and CSF Abeta
      were measured in cognitively normal, mild cognitive impairment (MCI), and
      Alzheimer's disease participants (n = 374) from the Alzheimer's Disease
      Neuroimaging Initiative. We also compared Abeta measurements in a separate group
      with serial CSF measurements over 3.1 +/- 0.8 years that preceded a single
      florbetapir session. Additional biomarker and cognitive data allowed us to
      further examine profiles of discordant cases. RESULTS: Florbetapir and CSF Abeta
      were inversely correlated across all diagnostic groups, and dichotomous
      measurements were in agreement in 86% of subjects. Among subjects showing the
      most disagreement, the 2 discordant groups had different profiles: the
      florbetapir(+) /CSF Abeta(-) group was larger (n = 13) and was made up of only
      normal and early MCI subjects, whereas the florbetapir(-) /CSF Abeta(+) group was
      smaller (n = 7) and had poorer cognitive function and higher CSF tau, but no
      ApoE4 carriers. In the longitudinal sample, we observed both stable longitudinal
      CSF Abeta trajectories and those actively transitioning from normal to abnormal,
      but the final CSF Abeta measurements were in good agreement with florbetapir
      cortical retention. INTERPRETATION: CSF and amyloid PET measurements of Abeta
      were consistent in the majority of subjects in the cross-sectional and
      longitudinal populations. Based on our analysis of discordant subjects, the
      available evidence did not show that CSF Abeta regularly becomes abnormal prior
      to fibrillar Abeta accumulation early in the course of disease.

PMID- 23536397
TI  - Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in
      household water and biofilm samples of patients in the United States with
      Mycobacterium avium complex respiratory disease.
AB  - Recent studies have shown that respiratory isolates from pulmonary disease
      patients and household water/biofilm isolates of Mycobacterium avium could be
      matched by DNA fingerprinting. To determine if this is true for Mycobacterium
      intracellulare, household water sources for 36 patients with Mycobacterium avium
      complex (MAC) lung disease were evaluated. MAC household water isolates from
      three published studies that included 37 additional MAC respiratory disease
      patients were also evaluated. Species identification was done initially using
      nonsequencing methods with confirmation by internal transcribed spacer (ITS)
      and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by
      nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm
      samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M.
      intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%)
      household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e.,
      isolates positive with a MAC probe but negative with species-specific M. avium
      and M. intracellulare probes), and 3 (7%) were M. avium; none were M.
      intracellulare. In comparison, M. avium was recovered from 141 water/biofilm
      samples. These results indicate that M. intracellulare lung disease in the United
      States is acquired from environmental sources other than household water.
      Nonsequencing methods for identification of nontuberculous mycobacteria
      (including those of the MAC) might fail to distinguish closely related species
      (such as M. intracellulare and M. chimaera). This is the first report of M.
      chimaera recovery from household water. The study underscores the importance of
      taxonomy and distinguishing the many species and subspecies of the MAC.

PMID- 23536398
TI  - Dietzia papillomatosis bacteremia.
AB  - The clinical significance of Dietzia papillomatosis is for the moment limited to
      the rare skin disease confluent and reticulated papillomatosis. We present a case
      of infection with D. papillomatosis in a 2-year-old boy with known syringomyelia.
      The microbiological diagnosis was done using 16S rRNA gene sequencing. This is
      the first report of bacteremia with D. papillomatosis.

PMID- 23536399
TI  - Quantitative PCR for detection of Shigella improves ascertainment of Shigella
      burden in children with moderate-to-severe diarrhea in low-income countries.
AB  - Estimates of the prevalence of Shigella spp. are limited by the suboptimal
      sensitivity of current diagnostic and surveillance methods. We used a
      quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533
      children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or
      without moderate-to-severe diarrhea (MSD). We compared the results from
      conventional culture to those from qPCR for the Shigella ipaH gene. Using MSD as
      the reference standard, we determined the optimal cutpoint to be 2.9 * 10(4) ipaH
      copies per 100 ng of stool DNA for set 1 (n = 877). One hundred fifty-eight (18%)
      specimens yielded >2.9 * 10(4) ipaH copies. Ninety (10%) specimens were positive
      by traditional culture for Shigella. Individuals with >= 2.9 * 10(4) ipaH copies
      have 5.6-times-higher odds of having diarrhea than those with <2.9 * 10(4) ipaH
      copies (95% confidence interval, 3.7 to 8.5; P < 0.0001). Nearly identical
      results were found using an independent set of samples. qPCR detected 155
      additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172
      cases detected by culture in both samples. Among a subset (n = 2,874) comprising
      MSD cases and their age-, gender-, and location-matched controls, the fraction of
      MSD cases that were attributable to Shigella infection increased from 9.6% (n =
      129) for culture to 17.6% (n = 262) for qPCR when employing our cutpoint. We
      suggest that qPCR with a cutpoint of approximately 1.4 * 10(4) ipaH copies be the
      new reference standard for the detection and diagnosis of shigellosis in children
      in low-income countries. The acceptance of this new standard would substantially
      increase the fraction of MSD cases that are attributable to Shigella.

PMID- 23536400
TI  - Development of a singleplex PCR assay for rapid identification and
      differentiation of Cryptococcus neoformans var. grubii, Cryptococcus neoformans
      var. neoformans, Cryptococcus gattii, and hybrids.
AB  - A singleplex PCR assay using a single primer pair targeting the putative sugar
      transporter gene was developed here to distinguish Cryptococcus neoformans var.
      grubii, Cryptococcus neoformans var. neoformans, and Cryptococcus gattii
      according to the distinct size of the amplicon. The interspecies and
      intravarietal hybrids were also characterized on the basis of distinct combined
      profiles of amplicons. This PCR assay is a rapid, simple, and reliable approach
      suitable for laboratory diagnoses and large-scale epidemiologic studies.

PMID- 23536401
TI  - Molecular characterization of Achromobacter isolates from cystic fibrosis and non
      cystic fibrosis patients in Madrid, Spain.
AB  - Multilocus sequence typing and nrdA sequence analysis identified 6 different
      species or genogroups and 13 sequence types (STs) among 15 Achromobacter isolates
      from cystic fibrosis (CF) patients and 7 species or genogroups and 11 STs among
      11 isolates from non-CF patients. Achromobacter xylosoxidans was the most
      frequently isolated species among CF patients.

PMID- 23536402
TI  - Comparison of the Vitek 2, MicroScan, and Etest methods with the agar dilution
      method in assessing colistin susceptibility of bloodstream isolates of
      Acinetobacter species from a Korean university hospital.
AB  - We evaluated three commercial colistin susceptibility testing methods using 213
      bloodstream Acinetobacter isolates identified by gene sequencing. Compared to the
      agar dilution reference method, excellent categorical agreements (both 99.1%)
      were observed using Vitek 2 and Etest, compared to 87.3% (95.7% for Acinetobacter
      baumannii and 80.7% for non-baumannii Acinetobacter isolates) using MicroScan.

PMID- 23536403
TI  - First case of Pseudoclavibacter bifida bacteremia in an immunocompromised host
      with chronic obstructive pulmonary disease (COPD).
AB  - Pseudoclavibacter spp. are Gram-positive, aerobic, catalase-positive, coryneform
      bacteria belonging to the family of Microbacteriaceae. Identification of these
      species with conventional biochemical assays is difficult. This case report of a
      Pseudoclavibacter bifida bacteremia occurring in an immunocompromised host
      diagnosed with an acute exacerbation of chronic obstructive pulmonary disease,
      with a lethal outcome, confirms that this organism may be a human pathogen.

PMID- 23536404
TI  - Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy
      in a patient with drug-induced hypersensitivity syndrome.
AB  - The present case provides direct evidence of human herpesvirus 6 reactivation in
      resected lymph node tissue in a patient with drug-induced hypersensitivity
      syndrome. This case clearly demonstrates that appropriate pathological evaluation
      of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics
      malignant lymphoma in clinical, radiological, and pathological findings, is
      required.

PMID- 23536405
TI  - A pragmatic approach to HIV-1 drug resistance determination in resource-limited
      settings by use of a novel genotyping assay targeting the reverse transcriptase
      encoding region only.
AB  - In resource-limited settings (RLS), reverse transcriptase (RT) inhibitors form
      the backbone of first-line treatment regimens. We have developed a simplified HIV
      1 drug resistance genotyping assay targeting the region of RT harboring all major
      RT inhibitor resistance mutation positions, thus providing all relevant
      susceptibility data for first-line failures, coupled with minimal cost and labor.
      The assay comprises a one-step RT-PCR amplification reaction, followed by
      sequencing using one forward and one reverse primer, generating double-stranded
      coverage of RT amino acids (aa) 41 to 238. The assay was optimized for all major
      HIV-1 group M subtypes in plasma and dried blood spot (DBS) samples using a panel
      of reference viruses for HIV-1 subtypes A to D, F to H, and circulating
      recombinant form 01_AE (CRF01_AE) and applied to 212 clinical plasma samples and
      25 DBS samples from HIV-1-infected individuals from Africa and Europe. The assay
      was subsequently transferred to Uganda and applied locally on clinical plasma
      samples. All major HIV-1 subtypes could be detected with an analytical
      sensitivity of 5.00E+3 RNA copies/ml for plasma and DBS. Application of the assay
      on 212 clinical samples from African subjects comprising subtypes A to D, F to H
      (rare), CRF01_AE, and CRF02_AG at a viral load (VL) range of 6.71E+2 to 1.00E+7
      (median, 1.48E+5) RNA copies/ml was 94.8% (n = 201) successful. Application on
      clinical samples in Uganda demonstrated a comparable success rate. Genotyping of
      clinical DBS samples, all subtype C with a VL range of 1.02E+3 to 4.49E+5
      (median, 1.42E+4) RNA copies/ml, was 84.0% successful. The described assay
      greatly reduces hands-on time and the costs required for genotyping and is ideal
      for use in RLS, as demonstrated in a reference laboratory in Uganda and its
      successful application on DBS samples.

PMID- 23536407
TI  - Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium
      chimaera.
AB  - Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous
      mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly
      growing NTM, however, are lacking. We present here one case of PVE and one case
      of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified
      polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera
      strains. Both patients had heart surgery 2 years apart from each other. A
      nosocomial link was not detected.

PMID- 23536406
TI  - Does neutralization of gastric aspirates from children with suspected
      intrathoracic tuberculosis affect mycobacterial yields on MGIT culture?
AB  - The microbiological confirmation of pulmonary tuberculosis in children relies on
      cultures of gastric aspirate (GA) specimens. Conventionally, GAs are neutralized
      to improve culture yields of mycobacteria. However, there are limited data to
      support this practice. To study the utility of neutralization of GAs with sodium
      bicarbonate in children with intrathoracic tuberculosis, a total of 116 children
      of either sex, aged 6 months to 14 years (median age, 120 months; interquartile
      range [IQR], 7 to 192 months), underwent gastric aspiration on 2 consecutive
      days. Gastric aspirates were divided into two aliquots, and only one aliquot was
      neutralized with 1% sodium bicarbonate. Both aliquots were processed for smear
      and culture examinations. Out of the 232 gastric aspirates, 12 (5.17%) were acid
      fast bacilli (AFB) smear positive. There were no differences in smear positivity
      rates from samples with or without neutralization. The yield of Mycobacterium
      tuberculosis on a Bactec MGIT 960 culture system was significantly lower in the
      neutralized samples (16.3% [38/232]) than in the nonneutralized samples (21.5%
      [50/232]) (P = 0.023). There was no significant difference between the
      neutralized and the nonneutralized samples in time to detection using the MGIT
      960 system (average, 24.6 days; IQR, 12 to 37 days) (P = 0.9). The contamination
      rates were significantly higher in the neutralized samples than in the
      nonneutralized samples (17.2% [40/232] versus 3.9% [9/232]) (P = 0.001). The
      agreement for positive mycobacterial culture between the two approaches was 66.5%
      (P = 0.001). Hence, we recommend that gastric aspirate samples not be neutralized
      with sodium bicarbonate prior to culture for M. tuberculosis.

PMID- 23536408
TI  - Use of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry to resolve complex clinical cases of patients with recurrent
      bacteremias.
AB  - Matrix-assisted laser desorption-ionization time of flight mass spectrometry
      (MALDI-TOF MS) is a rapid and accurate method of identifying microorganisms.
      Throughout Europe, it is already in routine use but has not yet been widely
      implemented in the United States, pending FDA approval. Here, we describe two
      medically complex patients at a large tertiary-care academic medical center with
      recurring bacteremias caused by distinct but related species. Bacterial
      identifications were initially obtained using the Vitek-2 system with the GPI
      card for Enterococcus and the API system for staphylococci. Initial results
      misled clinicians as to the source and proper management of these patients.
      Retrospective investigation with MALDI-TOF MS clarified the diagnosis by
      identifying a single microorganism as the pathogen in each case. To our
      knowledge, this is one of the first reports in the United States demonstrating
      the use of MALDI-TOF MS to facilitate the clinical diagnosis in patients with
      recurrent bacteremias of unclear source.

PMID- 23536409
TI  - Detection of IMP metallo-beta-lactamase in carbapenem-nonsusceptible
      Enterobacteriaceae and non-glucose-fermenting Gram-negative rods by
      immunochromatography assay.
AB  - Metallo-beta-lactamases (MBLs) are transmissible carbapenemases of increasing
      prevalence in Gram-negative bacteria among health care facilities worldwide.
      Control of the further spread of these carbapenem-resistant bacteria relies on
      clinical microbiological laboratories correctly identifying and classifying the
      MBLs. In this study, we evaluated a simple and rapid method for detecting IMP,
      the most prevalent MBL in Japan. We used an immunochromatography (IC) assay for
      181 carbapenem-nonsusceptible (CNS) (nonsusceptible to imipenem or meropenem)
      strains comprising 74 IMP-producing and 33 non-IMP-producing strains of non
      glucose-fermenting Gram-negative rods (NFGNR), as well as 64 IMP-producing and 10
      non-IMP-producing Enterobacteriaceae strains. The IC assay results were compared
      to those from the double-disk synergy test (DDST), the MBL Etest, and the
      modified Hodge test (MHT) (only for Enterobacteriaceae). The IMP type was
      confirmed by specific PCR and direct sequencing. The IC assay detected all of the
      IMP-type MBLs, including IMP-1, -2, -6, -7, -10, -11, -19, -20, and -22 and IMP
      40, -41, and -42 (new types), with 100% specificity and sensitivity against all
      strains tested. Although the sensitivity and specificity values for the DDST and
      MHT were equivalent to those for the IC assay, the MBL Etest was positive for
      only 87% of NFGNR and 31% of Enterobacteriaceae due to the low MIC of imipenem,
      causing an indeterminate evaluation. These results indicated that the IC assay
      might be a useful alternative to PCR for IMP MBL detection screening.

PMID- 23536410
TI  - The mechanism of stereospecific C-H oxidation by Fe(Pytacn) complexes:
      bioinspired non-heme iron catalysts containing cis-labile exchangeable sites.
AB  - A detailed mechanistic study of the hydroxylation of alkane C-H bonds using H2O2
      by a family of mononuclear non heme iron catalysts with the formula
      [Fe(II)(CF3SO3)2(L)] is described, in which L is a tetradentate ligand containing
      a triazacyclononane tripod and a pyridine ring bearing different substituents at
      the alpha and gamma positions, which tune the electronic or steric properties of
      the corresponding iron complexes. Two inequivalent cis-labile exchangeable sites,
      occupied by triflate ions, complete the octahedral iron coordination sphere. The
      C-H hydroxylation mediated by this family of complexes takes place with retention
      of configuration. Oxygen atoms from water are incorporated into hydroxylated
      products and the extent of this incorporation depends in a systematic manner on
      the nature of the catalyst, and the substrate. Mechanistic probes and isotopic
      analyses, in combination with detailed density functional theory (DFT)
      calculations, provide strong evidence that C-H hydroxylation is performed by
      highly electrophilic [Fe(V)(O)(OH)L] species through a concerted asynchronous
      mechanism, involving homolytic breakage of the C-H bond, followed by rebound of
      the hydroxyl ligand. The [Fe(V)(O)(OH)L] species can exist in two tautomeric
      forms, differing in the position of oxo and hydroxide ligands. Isotopic-labeling
      analysis shows that the relative reactivities of the two tautomeric forms are
      sensitively affected by the alpha substituent of the pyridine, and this
      reactivity behavior is rationalized by computational methods.

PMID- 23536412
TI  - Standardizing preanalytical variables for molecular cytopathology.

PMID- 23536411
TI  - Does parental anxiety cause biases in the processing of child-relevant threat
      material?
AB  - OBJECTIVES: Anxiety leads to biases in processing personally relevant
      information. This study set out to examine whether anxious parents also
      experience biases in processing child-relevant material. DESIGN AND METHODS:
      Ninety parents acted as a control condition, or received a social anxiety or
      child-related anxiety induction. They completed a task examining attentional
      biases in relation to child-threat words and social-threat words, and a task
      examining ability to categorize emotion in children's faces and voices. RESULTS:
      There was a trend indicating group differences in attentional bias towards social
      threat words, and this appears to have been only in the social anxiety condition,
      but not the child anxiety or control conditions. For child-threat words,
      attentional bias was present in the child anxiety condition, but not the social
      anxiety or control conditions. In the emotion recognition task, there was no
      difference between the control and child anxiety conditions, but the social
      anxiety condition were more likely to erroneously label children's faces and
      voices as sad. CONCLUSIONS: Parents' anxious biases may spill over into their
      child's world. PRACTITIONER POINTS: Parents' anxious biases may spill over into
      their child's world. Anxious parents may have attentional biases towards threats
      in their children's environment. Anxious parents may over-attribute negative
      emotion to children.

PMID- 23536413
TI  - Twitch and M-wave potentiation induced by intermittent maximal voluntary
      quadriceps contractions: differences between direct quadriceps and femoral nerve
      stimulation.
AB  - INTRODUCTION: The aim of this study was to investigate differences in twitch and
      M-wave potentiation in the quadriceps femoris when electrical stimulation is
      applied over the quadriceps muscle belly versus the femoral nerve trunk. METHODS:
      M-waves and mechanical twitches were evoked using direct quadriceps muscle and
      femoral nerve stimulation between 48 successive isometric maximal voluntary
      contractions (MVC) from 10 young, healthy subjects. Potentiation was investigated
      by analyzing the changes in M-wave amplitude recorded from the vastus medialis
      (VM) and vastus lateralis (VL) muscles and in quadriceps peak twitch force.
      RESULTS: Potentiation of twitch, VM M-wave, and VL M-wave were greater for
      femoral nerve than for direct quadriceps stimulation (P < 0.05). Despite a 50%
      decrease in MVC force, the amplitude of the M-waves increased significantly
      during exercise. CONCLUSIONS: In addition to enhanced electrogenic Na(+) -K(+)
      pumping, other factors (such as synchronization in activation of muscle fibers
      and muscle architectural properties) may significantly influence the magnitude of
      M-wave enlargement.

PMID- 23536414
TI  - Ulcerogenic and intestinal motility/transit stimulating actions of nevirapine in
      albino Wistar rats.
AB  - The antiretroviral is a non-nucleoside reverse transcriptase inhibitor of human
      immunodeficiency virus type 1. This study was undertaken to investigate the
      effect of nevirapine (NVP) administration on gastric acid secretion, pepsin
      secretion, mucosal secretion, intestinal motility, and transit using apparently
      healthy albino Wistar rats. Eighty albino Wistar rats (50-125 g body weight) from
      the start of the experiment were used for the study. Rats in the control group
      were fed normal rodent chow, while the NVP group was fed by gavage NVP (0.4 mg/kg
      body weight) two times daily (07:00 and 18:00 hours) in addition to normal rodent
      chow for 12 weeks. All animals were allowed free access to clean drinking water.
      Mean basal gastric output and peak acid output following histamine administration
      in the NVP-treated group were significantly higher (p < 0.001, respectively)
      compared to the control. Following cimetidine administration, there was
      significant decrease (p < 0.001) in peak acid output in the NVP-treated group
      compared to the control. The concentration of gastric pepsin, adherent mucus
      secretion, and mean value for ulcer score were significantly higher (p < 0.001)
      compared to their control group, respectively. There were significant increases
      (p < 0.05, respectively) in intestinal motility and basal contraction (p < 0.05)
      and increase in intestinal transit of the ileum of NVP-treated rats compared to
      their control, respectively. Results of the study suggest that NVP administration
      might provoke gastric ulceration in rats which may be caused by high pepsin, high
      basal acid output, and increased intestinal motility and transit.

PMID- 23536415
TI  - Reply to Win and Jenkins.

PMID- 23536416
TI  - Direct monitoring of initiation factor dynamics through formation of 30S and 70S
      translation-initiation complexes on a quartz crystal microbalance.
AB  - Translation initiation is a dynamic and complicated process requiring the
      building a 70S initiation complex (70S-IC) composed of a ribosome, mRNA, and an
      initiator tRNA. During the formation of the 70S-IC, initiation factors (IFs: IF1,
      IF2, and IF3) interact with a ribosome to form a 30S initiation complex (30S-IC)
      and a 70S-IC. Although some spectroscopic analyses have been performed, the
      mechanism of binding and dissociation of IFs remains unclear. Here, we employed a
      27 MHz quartz crystal microbalance (QCM) to evaluate the process of bacterial IC
      formation in translation initiation by following frequency changes (mass
      changes). IFs (IF1, IF2, and IF3), N-terminally fused to biotin carboxyl carrier
      protein (bio-BCCP), were immobilized on a Neutravidin-covered QCM plate. By using
      bio-BCCP-IF2 immobilized to the QCM, three steps of the formation of ribosomal
      initiation complex could be sequentially observed as simple mass changes in real
      time: binding of a 30S complex to the immobilized IF2, a recruitment of 50S to
      the 30S-IC, and formation of the 70S-IC. The kinetic parameters implied that the
      release of IF2 from the 70S-IC could be the rate-limiting step in translation
      initiation. The IF3-immobilized QCM revealed that the affinity of IF3 for the 30S
      complex decreased upon the addition of mRNA and fMet-tRNA(fMet) but did not lead
      to complete dissociation from the 30S-IC. These results suggest that IF3 binds
      and stays bound to ICs, and its interaction mode is altered during the formation
      of 30S-IC and 70S-IC and is finally induced to dissociate from ICs by 50S
      binding. This methodology demonstrated here is applicable to investigate the role
      of IFs in translation initiation driven by other pathways.

PMID- 23536417
TI  - A two-year randomized controlled trial of progressive resistance exercise for
      Parkinson's disease.
AB  - The effects of progressive resistance exercise (PRE) on the motor signs of
      Parkinson's disease have not been studied in controlled trials. The objective of
      the current trial was to compare 6-, 12-, 18-, and 24-month outcomes of patients
      with Parkinson's disease who received PRE with a stretching, balance, and
      strengthening exercise program. The authors conducted a randomized controlled
      trial between September 2007 and July 2011. Pairs of patients matched by sex and
      off-medication scores on the Unified Parkinson's Disease Rating Scale, motor
      subscale (UPDRS-III), were randomly assigned to the interventions with a 1:1
      allocation ratio. The PRE group performed a weight-lifting program. The modified
      fitness counts (mFC) group performed a stretching, balance, and strengthening
      exercise program. Patients exercised 2 days per week for 24 months at a gym. A
      personal trainer directed both weekly sessions for the first 6 months and 1
      weekly session after 6 months. The primary outcome was the off-medication UPDRS
      III score. Patients were followed for 24 months at 6-month intervals. Of 51
      patients, 20 in the PRE group and 18 in the mFC group completed the trial. At 24
      months, the mean off-medication UPDRS-III score decreased more with PRE than with
      mFC (mean difference, -7.3 points; 95% confidence interval, -11.3 to -3.6;
      P<0.001). The PRE group had 10 adverse events, and the mFC group had 7 adverse
      events. PRE demonstrated a statistically and clinically significant reduction in
      UPDRS-III scores compared with mFC and is recommended as a useful adjunct therapy
      to improve Parkinsonian motor signs. (c) 2013 Movement Disorder Society. 

PMID- 23536418
TI  - [Penetrating gluteal injury due to sledging accident].
AB  - We present the case of a rare penetrating sledging injury. A 39-year-old male
      sitting upright had his sledge burst when sliding into a pit. A stick fractured
      from the sledge's sitting plate and perforated from the infragluteal fold up to
      the lumbosacral junction. The man arrived in a conscious and cardiovascular
      stable condition in the ER, where no clinical evidence of vascular,
      retroperitoneal and pelvic injury was obvious. The anal external sphincter was
      uninjured and competent although the perforation enabled a look onto its surface.
      The foreign body was removed without further bleeding. Sledging injuries
      typically carry blunt characteristics, mainly with neurotrauma or fracture
      dislocations. As penetrating sledging injuries are exceptionally rare, strategies
      are discussed.

PMID- 23536419
TI  - Immunosuppression for Mooren's ulcer: evaluation of the stepladder approach-
      topical, oral and intravenous immunosuppressive agents.
AB  - AIM: To evaluate a step ladder approach for immunosuppressive regimen for
      Mooren's ulcer. MATERIAL AND METHODS: We retrospectively analysed patients of
      Mooren's ulcer presenting to a tertiary care centre in south India from 1987 to
      2010. Patients were analysed for the age, disease severity at time of
      presentation in terms of the quadrants of peripheral corneal involvement and
      amount of peripheral corneal thinning. According to the disease severity,
      patients were instituted either topical steroids (prednisolone acetate 1%) single
      agent or in combination with oral steroids (prednisolone 1-1.5 mg/kg/day), oral
      immunomodulators (methotrexate 7.5-12.5 mg/week), intravenous pulsed methyl
      prednisolone 1 g or pulsed cyclophosphamide 1 g. The main outcome measure was
      control of disease activity. RESULTS: Topical steroids as a single therapy had a
      disease resolution rate in 76% of the cases. Cases that required oral steroids,
      oral methotrexate, intravenous pulsed methyl prednisolone and combination of
      pulsed methyl prednisolone and cyclophosphamide had a resolution rate of 86%,
      78.5%, 71.4% and 73.3%, respectively. The most common complication was secondary
      infection. Most of the cases that failed therapy had perforation of the cornea
      and required corneal transplantation. CONCLUSIONS: An aggressive
      immunosuppressive regimen that is tailor made based on disease severity as a
      first line of therapy improves the chances of disease control even in cases of
      aggressive Mooren's ulcer.

PMID- 23536420
TI  - Central toxic keratopathy: a clinical case series.
AB  - PURPOSE: To describe clinically, a case series of central toxic keratopathy
      (CTK), and contribute with one possible aetiology of this entity. METHODS: A
      retrospective observational case series, which included 12 eyes diagnosed with
      CTK after undergoing laser refractive surgery in situ keratomileusis (LASIK).
      RESULTS: From a total of 28 eyes that underwent LASIK in the same week, 12
      develop CTK. The mean time of the diagnostic was 4 days after surgery. The
      resolution time had an interval between 1, 3 and 9 months, and an average of 4.6
      months. The occurrence of CTK cases coincided with the change of the brand of
      surgical gloves, and no further cases were found after their replacement.
      CONCLUSIONS: The CTK clinical findings are well described, but with a yet unknown
      origin. It seems clear that it does not require specific treatment. It is
      possible that there might be a relationship between a substance of the gloves and
      CTK. Further studies are needed to know all the details of this process.

PMID- 23536421
TI  - Contralateral lateral rectus recession versus recess-resect for recurrent
      exotropia after unilateral recess-resect.
AB  - BACKGROUND: To compare outcomes following contralateral lateral rectus (LR)
      recession and recess-resect (RR) procedures for recurrent exotropia of 20-25
      prism dioptres (PD) after unilateral RR. METHODS: 39 subjects were included in
      this retrospective study. All underwent, as a primary surgery for intermittent
      exotropia, unilateral RR on the non-dominant eye. They were assigned to the
      subsequent contralateral LR recession (LR, n=19) or RR (n=20) group for recurrent
      exotropia of 20-25 PD. Surgical success was defined as alignment between 5 PD
      esodeviation and 10 PD exodeviation. RESULTS: The mean follow-up duration after
      the reoperation was 32.3+/-26.4 months in the LR group and 30.5+/-26.8 in the RR
      group (p=0.945). The mean deviation angles at postoperative 1 day were -0.7 PD
      (overcorrection) in the LR group and -4.3 PD in the RR group (p=0.047). The
      deviation angles at 3 and 6 months postoperatively were not significant (p=0.771,
      p=0.923). The final successful outcome was achieved in 63.2% of patients in the
      LR group and in 65% of patients in the RR group (p=0.905). CONCLUSIONS:
      Contralateral LR recession was found to be a safe and effective procedure for the
      treatment of recurrent exotropia of 20-25 PD after unilateral RR for intermittent
      exotropia. With LR recession, the intentional overcorrection in the immediate
      postoperative period could be avoided.

PMID- 23536422
TI  - Aortic regurgitation and device closure of ASD or PFO.

PMID- 23536423
TI  - Unique structural properties of 2,4,6-tri-tert-butylanilide: isomerization and
      switching between separable amide rotamers through the reaction of anilide
      enolates.
AB  - Herein, we report a unique structural property of 2,4,6-tri-tert-butylanilide,
      which can be separated into its amide rotamers at room temperature.
      Interconversion between the rotamers of anilide enolates occurs readily at room
      temperature and their reaction with electrophiles gives mixtures of the rotamers
      in a ratio that depends on the reactivity of the corresponding electrophile. That
      is, the reaction of the 2,4,6-tri-tert-butylacetanilide enolate with reactive
      electrophiles, such as allyl bromide or protic acids, gives mixtures of the
      anilide rotamers in which the E rotamer is the major component, whereas less
      reactive electrophiles, such as 1-bromopropane and 2-iodopropane, yield mixtures
      of the rotamers in which the Z rotamer is the major component. The rotameric
      ratio of the product is also strongly dependent on the reactivity of the anilide
      enolate. Switching between the anilide rotamers can be achieved through
      protonation of a less-reactive enolate by a less-reactive protic acid and thermal
      isomerization of the anilide.

PMID- 23536424
TI  - Fine-needle aspiration diagnosis of lymphomas with signet ring cell features:
      potential pitfalls and solutions.
AB  - BACKGROUND: Lymphoma with signet ring cell features (LSF) is a rare morphologic
      variant of non-Hodgkin lymphoma. Although it has been well documented in the
      surgical pathology literature, to the best of the authors's knowledge, the
      features of LSF in fine-needle aspiration (FNA) samples have rarely been
      reported. An accurate cytologic diagnosis of LSF is of important therapeutic
      significance. METHODS: The authors retrospectively reviewed 7 FNA cases of LSF
      for cytologic features, ancillary studies, corresponding histologic findings, and
      the patients' clinical and radiologic information to illustrate the diagnostic
      clues and potential pitfalls. RESULTS: The final diagnoses, based on a
      multidisciplinary approach, were follicular lymphoma (5 patients), large B-cell
      lymphoma of follicular center cell origin (1 patient), and low-grade B-cell
      lymphoma with plasmacytoid features (1 patient). FNAs were obtained from both
      lymph node and extranodal sites. Common cytologic features included various
      percentages of signet ring cells in a background of nonvacuolated lymphomatous
      cells, lymphoglandular bodies, and cytoplasmic rings. The majority of signet ring
      cells contained a single, large, clear intracytoplasmic vacuole that pushed the
      nucleus laterally whereas fewer cells contained >= 2 vacuoles that indented the
      nucleus into a scalloped or stellate configuration. These cells resemble, to some
      degree, other lesions with signet ring cell features. One of the diagnostic clues
      of LSF was the similarity in nuclear details between signet ring cells and
      surrounding nonvacuolated lymphoid cells. CONCLUSIONS: Familiarity with cytologic
      features, correlation with clinical/radiologic information, and ancillary studies
      are important for an accurate diagnosis of LSF and for distinguishing it from
      other lesions with signet ring cell features in FNA samples.

PMID- 23536425
TI  - [Clinical, biological and therapeutic profile of anemia by vitamin B12 deficiency
      in the department of hematology of Marrakech (Morocco)].
AB  - The aim of this study is to examine retrospectively the clinical, biological and
      treatment features of anemia by vitamin B12 deficiency in the Hematology
      department of CHU Mohamed VI Marrakech. We report the results of a retrospective
      study conducted during six years (2005-2010). It included all patients with
      anemia (with or without thrombocytopenia or leukopenia) associated with vitamin
      B12 levels <200 pg / ml. One hundred twenty one cases were analyzed. The average
      age of patients was 62 years (38-89 years) with a female predominance (sex ratio
      F/M: 1.3). The clinical symptomatology is dominated by pallor (97.5%),
      cardiovascular signs (46%) and digestive symptoms (34.7%). Neurological signs
      were noted in 17.3% of cases. The blood count showed anemia (hemoglobin: mean=
      6.9 g/dl), macrocythemia (MCV: mean= 109 fl). Leukopenia was noted in 35 patients
      (29%), thrombocytopenia in 34 patients (28%) and pancytopenia in 21 patients
      (17,3%). The average vitamin B12 was 72 pg/ml. The causes of B12 deficiency are
      pernicious anemia (43%), food-cobalamin malabsorption (43%), and in 14% of cases
      no etiology was found. Gastritis was found in 82.7% of our patients and
      Helicobacter pylori (HP) infection in 72.7% of cases. Reticulocyte crisis was
      observed after parenteral administration of hydroxocobalamine within an average
      of 8 days and normalization of blood counts, in all patients, within an average
      of 51 days. In patients with HP infection, eradication therapy of HP was
      performed. The cure rate of the HP is 90%.

PMID- 23536426
TI  - Is the reported modifying effect of 8q23.3 and 11q23.1 on colorectal cancer risk
      for MLH1 mutation carriers valid?

PMID- 23536428
TI  - Insights into the intramolecular donor stabilisation of organostannylene
      palladium and platinum complexes: syntheses, structures and DFT calculations.
AB  - The syntheses of the transition metal complexes cis-[(4-tBu-2,6
      {P(O)(OiPr)2}2C6H2SnCl)2MX2] (1, M = Pd, X = Cl; 2, M = Pd, X = Br; 3, M = Pd, X
      = I; 4, M = Pt, X = Cl), cis-[{2,6-(Me2NCH2)2C6H3SnCl}2MX2] (5, M = Pd, X = I; 6,
      M = Pt, X = Cl), trans-[{2,6-(Me2NCH2)2C6H3SnI}2PtI2] (7) and trans-[(4-tBu-2,6
      {P(O)(OiPr)2}2C6H2SnCl)PdI2]2 (8) are reported. Also reported is the
      serendipitous formation of the unprecedented complexes trans-[(4-tBu-2,6
      {P(O)(OiPr)2}2C6H2SnCl)2Pt(SnCl3)2] (10) and [(4-tBu-2,6
      {P(O)(OiPr)2}2C6H2SnCl)3Pt(SnCl3)2] (11). The compounds were characterised by
      elemental analyses, (1)H, (13)C, (31)P, (119)Sn and (195)Pt NMR spectroscopy,
      single-crystal X-ray diffraction analysis, UV/Vis spectroscopy and, in the cases
      of compounds 1, 3 and 4, also by Mossbauer spectroscopy. All the compounds show
      the tin atoms in a distorted trigonal-bipyramidal environment. The Mossbauer
      spectra suggest the tin atoms to be present in the oxidation state III. The
      kinetic lability of the complexes was studied by redistribution reactions between
      compounds 1 and 3 as well as between 1 and cis-[{2,6-(Me2 NCH2)2C6H3SnCl}2PdCl2].
      DFT calculations provided insights into both the bonding situation of the
      compounds and the energy difference between the cis and trans isomers. The latter
      is influenced by the donor strength of the pincer-type ligands.

PMID- 23536427
TI  - Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with
      ptosis.
AB  - INTRODUCTION: Several studies have reported high diagnostic sensitivity and
      specificity for the ice test in myasthenia gravis. All of the studies employed a
      case-control design, in which the diagnosis was already known at the time of the
      test for both patients and controls, leading to case selection bias. This
      suggests that the available literature substantially overestimates the diagnostic
      utility of these tests. METHODS: A retrospective cohort study without selection
      bias was performed to examine the sensitivity and specificity of the ice test.
      The sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of the ice test were determined by means of a 2 * 2 table.
      RESULTS: The ice test has a sensitivity of 0.92 (95% CI 0.62-1.00), specificity
      of 0.79 (95% CI 0.56-1.00), PPV of 0.73 (95% CI 0.48-0.90), and NPV of 0.94 (95%
      CI 0.70-1.00). CONCLUSIONS: Due to its high negative predictive value the ice
      test is still a reliable and useful bed-side test.

PMID- 23536429
TI  - Five-year outcomes of self-expanding nitinol stent implantation for chronic total
      occlusion of the superficial femoral and proximal popliteal artery.
AB  - OBJECTIVE: To investigate the 5-year patency rates and predictors of restenosis
      after self-expanding nitinol stent implantation for chronic total occlusion (CTO)
      in superficial femoral and proximal popliteal artery (SFPA) lesions. BACKGROUND:
      Outcomes and long-term patency rates after self-expanding nitinol stent for CTO
      in the SFPA lesions have not been clarified. METHODS: From January 2004 to
      December 2009, 861 serial arteriosclerosis obliterans patients, 1,017 limbs,
      underwent endovascular therapy with implantation of a self-expanding nitinol
      stent for SFPA lesions at four institutions in Japan. Of the cohort, 352
      patients, 383 limbs, had self-expanding nitinol stents implanted for CTOs in the
      SFPA and were followed for 5 years. We retrospectively investigated patency rate
      and multivariate predictors associated with restenosis. RESULTS: Mean age was 72
      +/- 9 years and 31% were female patients. In total, 58% of the patients had
      diabetes mellitus and 25% were patients with critical limb ischemia. Occluded
      length was 194 +/- 89 mm, mean total stent length was 198 +/- 7 mm, and mean
      stent diameter was 7.1 +/- 0.9 mm. Five-year primary and secondary patency rates
      were 51.8 and 79.5%, respectively, and the rates of freedom from bypass surgery,
      major or minor amputation, and all-cause death were 96.1, 96.2, and 78.4%,
      respectively. Female gender (odds ratio, 1.95; P = 0.0051) and mean stent
      diameter (odds ratio, 0.77; P = 0.0324) were factors strongly associated with
      restenosis. CONCLUSIONS: Women and patients requiring small stents failed to
      maintain primary patency when treated with self-expanding nitinol stents for CTO
      lesions in the SFPA. Although primary patency was low, the secondary patency rate
      was acceptable.

PMID- 23536430
TI  - The VPS35 gene and Parkinson's disease.
AB  - Parkinson's disease (PD), the second most common age-related neurodegenerative
      disease, is characterized by loss of dopaminergic and nondopaminergic neurons,
      leading to a variety of motor and nonmotor symptoms. In addition to environmental
      factors, genetic predisposition and specific gene mutations have been shown to
      play an important role in the pathogenesis of this disorder. Recently, the
      identification of the vacuolar protein sorting 35 homolog gene (VPS35), linked to
      autosomal dominant late-onset PD, has provided new clues to the pathogenesis of
      PD. Here we discuss the VPS35 gene, its protein function, and various pathways
      involved in Wnt/beta-catenin signaling and in the role of DMT1 mediating the
      uptake of iron and iron translocation from endosomes to the cytoplasm. Further
      understanding of these mechanisms will undoubtedly provide new insights into the
      pathogenic mechanisms of PD and may lead to prevention and better treatment of
      the disorder.

PMID- 23536431
TI  - Dysfunction of protein homeostasis in myotonic dystrophies.
AB  - Neuromuscular diseases Myotonic Dystrophies type 1 and type 2 (DM1 and DM2) are
      caused by unstable CTG and CCTG repeat expansions and have highly complex
      molecular mechanisms. DM1 is caused by the expansion of CTG repeats in the 3' UTR
      of the gene coding for Dystrophia Myotonica-Protein Kinase (DMPK). In DM2,
      intronic CCTG repeats are located in a gene encoding the Zinc Finger Protein 9
      (ZNF9, also known as Cellular Nucleic Acid Binding Protein, CNBP). Both
      expansions cause pathologies through RNA CUG and CCUG repeats, which have toxic
      effects on the processing of many RNAs in the patients' tissues. The pathogenic
      role of CUG and CCUG repeats in the mis-regulation of alternative splicing,
      mediated by RNA-binding proteins CUGBP1 and MBNL1, has been discussed in a number
      of excellent reviews. Recent reports suggest that mutant RNA repeats affect
      several other RNA-binding proteins such as Staufen1 and the DEAD-box RNA helicase
      p68 (DDX5). Since CUGBP1, Staufen1 and p68 have many functions in cytoplasm,
      including regulation of protein translation, it is predicted that the alterations
      of these proteins in DM cells might have a toxic effect on global protein
      turnover. In this mini-review, we will summarize observations showing the role of
      RNA-binding proteins, CUGBP1 and ZNF9, in protein turnover in DM1 and in DM2. We
      will also discuss a possible role of misbalanced protein turnover in the age
      dependent progression of DM1 and in a late onset of DM2.

PMID- 23536432
TI  - Synthesis and structures of ansa-titanocene complexes with diatomic bridging
      units for overall water splitting.
AB  - The synthesis of a series of ansa-titanocene dichlorides [Cp'2TiCl2] (Cp' =
      bridged eta(5)-tetramethylcyclopentadienyl) and the corresponding titanocene
      bis(trimethylsilyl)acetylene complexes [Cp'2Ti(eta(2)-Me3SiC2SiMe3)] is
      described. The ethanediyl-bridged complexes [C2H4(C5Me4)2TiCl2] (2-Cl2) and
      [C2H4(C5Me4)2Ti(eta(2)-Me3SiC2SiMe3)] (2-btmsa; btmsa = eta(2)-Me3SiC2SiMe3) can
      be obtained from the hitherto unknown calcocenophane complex
      [C2H4(C5Me4)2Ca(THF)2] (1). Furthermore, a heterodiatomic bridging unit
      containing both, a dimethylsilyl and a methylene group was introduced to yield
      the ansa-titanocene dichloride [Me2SiCH2(C5Me4)2TiCl2] (3-Cl2) and the
      bis(trimethylsilyl)acetylene complex [Me2SiCH2(C5Me4)2Ti(eta(2)-Me3SiC2SiMe3)] (3
      btmsa). Besides, tetramethyldisilyl- and dimethylsilyl-bridged metallocene
      complexes (structural motif 4 and 5, respectively) were prepared. All ansa
      titanocene alkyne complexes were reacted with stoichiometric amounts of water;
      the hydrolysis products were isolated as model complexes for the investigation of
      the elemental steps of overall water splitting. Compounds 1, 2-btmsa, 2-(OH)2, 3
      Cl2, 3-btmsa, 4-(OH)2, 3-alkenyl and 5-alkenyl were characterised by X-ray
      diffraction analysis.

PMID- 23536433
TI  - Student injuries in the dissecting room.
AB  - Cadaver dissection is the first opportunity for many students to practice
      handling human tissue and is their first exposure to the occupational hazards
      involved with this task. Few studies examine dissection room injuries to
      ascertain the dangers associated with dissecting. We performed a retrospective
      cohort analysis of dissection room injuries from four student cohorts over an
      eleven-year period (2001-2011), including second-year medical students, third
      year medical students, second-year dental students, and third-year science
      students. Injury data included activity causing injury, object responsible, and
      injury site. A total of 163 injuries during 70,039 hours of dissection were
      recorded, with 66 in third-year medical students, 42 in second-year medical
      students, 36 in third-year science students, and 16 in second-year dental
      students. The overall rate was 2.87 injuries per 1,000 dissection hours, with
      second-year medical students most frequently injured (5.5 injuries per 1,000
      hours); third-year medical students were least frequently injured (1.3 injuries
      per 1,000 hours). A significant difference in injury rates between student groups
      indicated a higher than expected injury rate to second-year medical students and
      lower than expected rates to third-year medical students. Injury rates increased
      for most groups between 2001-2006 and 2007-2011 periods. Most injuries (79%) were
      from scalpel cuts to the finger or thumb. This study provides injury rates for
      dissection room injuries to students, indicating differences in injury frequency
      between cohorts and an increase in injury rate over time. As scalpel cuts were
      the most likely injury mechanism, targeting scalpel handling with preventative
      strategies may reduce future injury risk.

PMID- 23536434
TI  - Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen
      resistant breast cancer: implications for treatment of advanced disease.
AB  - PURPOSE: There is compelling evidence to suggest that drugs that function as pure
      estrogen receptor (ER-alpha) antagonists, or that downregulate the expression of
      ER-alpha, would have clinical use in the treatment of advanced tamoxifen- and
      aromatase-resistant breast cancer. Although such compounds are currently in
      development, we reasoned, based on our understanding of ER-alpha pharmacology,
      that there may already exist among the most recently developed selective estrogen
      receptor modulators (SERM) compounds that would have usage as breast cancer
      therapeutics. Thus, our objective was to identify among available SERMs those
      with unique pharmacologic activities and to evaluate their potential clinical use
      with predictive models of advanced breast cancer. EXPERIMENTAL DESIGN: A
      validated molecular profiling technology was used to classify clinically relevant
      SERMs based on their impact on ER-alpha conformation. The functional consequences
      of these observed mechanistic differences on (i) gene expression, (ii) receptor
      stability, and (iii) activity in cellular and animal models of advanced endocrine
      resistant breast cancer were assessed. RESULTS: The high-affinity SERM
      bazedoxifene was shown to function as a pure ER-alpha antagonist in cellular
      models of breast cancer and effectively inhibited the growth of both tamoxifen
      sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene
      induced a unique conformational change in ER-alpha that resulted in its
      proteasomal degradation, although the latter activity was dispensable for its
      antagonist efficacy. CONCLUSION: Bazedoxifene was recently approved for use in
      the European Union for the treatment of osteoporosis and thus may represent a
      near-term therapeutic option for patients with advanced breast cancer.

PMID- 23536436
TI  - Identification and validation of a blood-based 18-gene expression signature in
      colorectal cancer.
AB  - PURPOSE: The early detection of colorectal cancer (CRC) is crucial for successful
      treatment and patient survival. However, compliance with current screening
      methods remains poor. This study aimed to identify an accurate blood-based gene
      expression signature for CRC detection. EXPERIMENTAL DESIGN: Gene expression in
      peripheral blood samples from 216 patients with CRC tumors and 187 controls was
      investigated in the study. We first conducted a microarray analysis to select
      candidate genes that were significantly differentially expressed between patients
      with cancer and controls. A quantitative reverse transcription PCR assay was then
      used to evaluate the expression of selected genes. A gene expression signature
      was identified using a training set (n = 200) and then validated using an
      independent test set (n = 160). RESULTS: We identified an 18-gene signature that
      discriminated the patients with CRC from controls with 92% accuracy, 91%
      sensitivity, and 92% specificity. The signature performance was further validated
      in the independent test set with 86% accuracy, 84% sensitivity, and 88%
      specificity. The area under the receiver operating characteristics curve was
      0.94. The signature was shown to be enriched in genes related to immune
      functions. CONCLUSIONS: This study identified an 18-gene signature that
      accurately discriminated patients with CRC from controls in peripheral blood
      samples. Our results prompt the further development of blood-based gene
      expression biomarkers for the diagnosis and early detection of CRC.

PMID- 23536435
TI  - Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib
      in children with newly diagnosed diffuse intrinsic pontine glioma.
AB  - PURPOSE: Testing of promising drug combinations is crucial in the treatment of
      diffuse intrinsic pontine glioma (DIPG). As the VEGF and platelet-derived growth
      factor (PDGF) pathways are critical in gliomas, we evaluated the safety, maximum
      tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of vandetanib, a
      VEGFR-2 inhibitor, combined with dasatinib, a potent PDGFR inhibitor, during and
      after radiotherapy in children with newly diagnosed DIPG. EXPERIMENTAL DESIGN:
      Dasatinib was started concurrently with radiotherapy. Vandetanib was started 8
      days later. We tested increasing doses of vandetanib (65 and 85 mg/m(2) once
      daily) and dasatinib (65 and 85 mg/m(2) twice daily). Dose-limiting toxicities
      were evaluated during the first 6 weeks of therapy. Plasma pharmacokinetics was
      obtained on days 8 and 42 +/- 3 in all patients and concomitantly with
      cerebrospinal fluid (CSF) when possible. Inhibition of targets of dasatinib in
      peripheral blood mononuclear cells (PBMC) was evaluated. RESULTS: Twenty-five
      patients were treated. Treatment was well tolerated. The median duration of
      treatment was 184 days. Diarrhea was the most significant toxicity. Three
      patients experienced substantial myelosuppression. The steady-state plasma
      pharmacokinetics of vandetanib was comparable with previous studies. Although the
      plasma exposure to dasatinib decreased from days 8 to 42, it remained similar to
      adult studies. CSF to plasma exposure of vandetanib and dasatinib were
      approximately 2% in 2 patients. Phosphorylated 70S6K decreased during therapy in
      PBMCs. CONCLUSIONS: The MTD of vandetanib and dasatinib in combination was 65
      mg/m(2) for each drug. Other studies are underway to test dasatinib and other
      PDGFR inhibitors alone or in combination for this deadly cancer.

PMID- 23536438
TI  - Infection and cancer: revaluation of the hygiene hypothesis.
AB  - Several studies have shown that persistent infections and inflammation can favor
      carcinogenesis. At the same time, certain types of pathogens and antitumor immune
      responses can decrease the risk of tumorigenesis or lead to cancer regression.
      Infectious agents and their products can orchestrate a wide range of host immune
      responses, through which they may positively or negatively modulate cancer
      development and/or progression. The factors that direct this dichotomous
      influence of infection-mediated immunity on carcinogenesis are not well
      understood. Even though not universal, several previous reports have investigated
      the inverse link of pathogen-induced "benign" inflammation to carcinogenesis and
      various other pathologies, ranging from autoimmune diseases to allergy and
      cancer. Several models and ideas are discussed in this review, including the
      impact of decreased exposure to pathogens, as well as the influence of pathogen
      load, the timing of infection, and the type of instigated immune response on
      carcinogenesis. These phenomena should guide future investigations into
      identifying novel targets within the microbial and host proteome, which will
      assist in the development of cancer therapeutics and vaccine remedies, analogous
      to earlier efforts based on helminthic components for the prevention and/or
      treatment of several pathologies.

PMID- 23536437
TI  - Temozolomide-mediated DNA methylation in human myeloid precursor cells:
      differential involvement of intrinsic and extrinsic apoptotic pathways.
AB  - PURPOSE: An understanding of how hematopoietic cells respond to therapy that
      causes myelosuppression will help develop approaches to prevent this potentially
      life-threatening toxicity. The goal of this study was to determine how human
      myeloid precursor cells respond to temozolomide (TMZ)-induced DNA damage.
      EXPERIMENTAL DESIGN: We developed an ex vivo primary human myeloid precursor
      cells model system to investigate the involvement of cell-death pathways using a
      known myelosuppressive regimen of O(6)-benzylguanine (6BG) and TMZ. RESULTS:
      Exposure to 6BG/TMZ led to increases in p53, p21, gamma-H2AX, and mitochondrial
      DNA damage. Increases in mitochondrial membrane depolarization correlated with
      increased caspase-9 and -3 activities following 6BG/TMZ treatment. These events
      correlated with decreases in activated AKT, downregulation of the DNA repair
      protein O(6)-methylguanine-DNA methyltransferase (MGMT), and increased cell
      death. During myeloid precursor cell expansion, FAS/CD95/APO1(FAS) expression
      increased over time and was present on approximately 100% of the cells following
      exposure to 6BG/TMZ. Although c-flipshort, an endogenous inhibitor of FAS
      mediated signaling, was decreased in 6BG/TMZ-treated versus control, 6BG-, or TMZ
      alone-treated cells, there were no changes in caspase-8 activity. In addition,
      there were no changes in the extent of cell death in myeloid precursor cells
      exposed to 6BG/TMZ in the presence of neutralizing or agonistic anti-FAS
      antibodies, indicating that FAS-mediated signaling was not operative.
      CONCLUSIONS: In human myeloid precursor cells, 6BG/TMZ-initiated apoptosis
      occurred by intrinsic, mitochondrial-mediated and not extrinsic, FAS-mediated
      apoptosis. Human myeloid precursor cells represent a clinically relevant model
      system for gaining insight into how hematopoietic cells respond to
      chemotherapeutics and offer an approach for selecting effective chemotherapeutic
      regimens with limited hematopoietic toxicity.

PMID- 23536439
TI  - NIK controls classical and alternative NF-kappaB activation and is necessary for
      the survival of human T-cell lymphoma cells.
AB  - PURPOSE: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of
      neoplasms with poor prognosis, a lack of effective therapies, and a largely
      unknown molecular pathology. Deregulated NF-kappaB activity has been associated
      with several lymphoproliferative diseases, but its importance in T-cell
      lymphomagenesis is poorly understood. We investigated the function of the NF
      kappaB-inducing kinase (NIK), in this pathway and its role as a potential
      molecular target in T-cell lymphomas. EXPERIMENTAL DESIGN: We used
      immunohistochemistry to analyze the expression of different NF-kappaB members in
      primary human PTCL samples and to study its clinical impact. With the aim of
      inhibiting the pathway, we used genetic silencing of NIK in several T-cell
      lymphoma cell lines and observed its effect on downstream targets and cell
      viability. RESULTS: We showed that the NF-kappaB pathway was activated in a
      subset of PTCLs associated with poor overall survival. NIK was overexpressed in a
      number of PTCL cell lines and primary samples, and a pivotal role for NIK in the
      survival of these tumor cells was unveiled. NIK depletion led to a dramatic
      induction of apoptosis in NIK-overexpressing cell lines and also showed a more
      pronounced effect on cell survival than inhibitor of kappa B kinase (IKK)
      knockdown. NIK silencing induced a blockage of both classical and alternative NF
      kappaB activation and reduced expression of several prosurvival and antiapoptotic
      factors. CONCLUSIONS: The results of the present study indicate that NIK could be
      a promising therapeutic target in these aggressive malignancies.

PMID- 23536440
TI  - Forests as promoters of terrestrial life-history strategies in East African
      amphibians.
AB  - Many amphibian lineages show terrestrialization of their reproductive strategy
      and breeding is partially or completely independent of water. A number of causal
      factors have been proposed for the evolution of terrestrialized breeding. While
      predation has received repeated attention as a potential factor, the influence of
      other factors such as habitat has never been tested using appropriate data or
      methods. Using a dataset that comprises 180 amphibian species from various East
      African habitats, we tested whether species occurring in different habitats show
      different patterns of terrestrialization in their breeding strategy. We recovered
      a significant association between terrestrialized breeding strategies and forest
      habitats. In general, forest seems to act as a facilitator, providing a
      permissive environment for the evolution of terrestrialized breeding strategies.
      However, while terrestrial oviposition is strongly correlated with lowland and
      montane forest habitat, complete terrestrial development is significantly
      correlated with montane forest only, indicating different selective pressures
      acting at different steps towards complete terrestrial development.

PMID- 23536441
TI  - Predator-prey body size relationships when predators can consume prey larger than
      themselves.
AB  - As predator-prey interactions are inherently size-dependent, predator and prey
      body sizes are key to understanding their feeding relationships. To describe
      predator-prey size relationships (PPSRs) when predators can consume prey larger
      than themselves, we conducted field observations targeting three aquatic
      hemipteran bugs, and assessed their body masses and those of their prey for each
      hunting event. The data revealed that their PPSR varied with predator size and
      species identity, although the use of the averaged sizes masked these effects.
      Specifically, two predators had slightly decreased predator-prey mass ratios
      (PPMRs) during growth, whereas the other predator specialized on particular sizes
      of prey, thereby showing a clear positive size-PPMR relationship. We discussed
      how these patterns could be different from fish predators swallowing smaller prey
      whole.

PMID- 23536442
TI  - Cross-cultural variation in women's preferences for cues to sex- and stress
      hormones in the male face.
AB  - Women in the UK prefer the faces of men with low levels of the stress hormone
      cortisol, and the relationship is moderated by the sex hormone testosterone. In a
      Latvian sample, however, women's preferences were not affected by cortisol, and
      the interaction with testosterone differed from that of the UK. To further
      explore cross-cultural variation in preferences for facial cues to sex- and
      stress-hormones, we tested the preferences of women from 13 countries for facial
      composites constructed to differ in combinations of the hormones. We found
      significant relationships between a measure of societal development (the United
      Nations human development index 2011) and preferences for cues to testosterone in
      the face, and the interaction between preferences for cues to testosterone and
      cortisol. We also found a significant relationship between preferences for cues
      to testosterone and a societal-level measure of parasite stress. We conclude that
      societal-level ecological factors influence the relative value of traits revealed
      by combinations of sex- and stress-hormones.

PMID- 23536443
TI  - Triassic-Jurassic mass extinction as trigger for the Mesozoic radiation of
      crocodylomorphs.
AB  - Pseudosuchia, one of the two main clades of Archosauria (Reptilia: Diapsida),
      suffered a major decline in lineage diversity during the Triassic-Jurassic (TJ)
      mass extinction (approx. 201 Ma). Crocodylomorpha, including living crocodilians
      and their extinct relatives, is the only group of pseudosuchians that survived
      into the Jurassic. We reassess changes in pseudosuchian morphological diversity
      (disparity) across this time interval, using considerably larger sample sizes
      than in previous analyses. Our results show that metrics of pseudosuchian
      disparity did not change significantly across the TJ boundary, contrasting with
      previous work suggesting low pseudosuchian disparity in the Early Jurassic
      following the TJ mass extinction. However, a significant shift in morphospace
      occupation between Late Triassic and Early Jurassic taxa is recognized,
      suggesting that the TJ extinction of many pseudosuchian lineages was followed by
      a major and geologically rapid adaptive radiation of crocodylomorphs. This marks
      the onset of the spectacularly successful evolutionary history of crocodylomorphs
      in Jurassic and Cretaceous ecosystems.

PMID- 23536444
TI  - Evidence for hearing loss in amblyopsid cavefishes.
AB  - The constant darkness of caves and other subterranean habitats imposes sensory
      constraints that offer a unique opportunity to examine evolution of sensory
      modalities. Hearing in cavefishes has not been well explored, and here we show
      that cavefishes in the family Amblyopsidae are not only blind but have also lost
      a significant portion of their hearing range. Our results showed that cave and
      surface amblyopsids shared the same audiogram profile at low frequencies but only
      surface amblyopsids were able to hear frequencies higher than 800 Hz and up to 2
      kHz. We measured ambient noise in aquatic cave and surface habitats and found
      high intensity peaks near 1 kHz for streams underground, suggesting no adaptive
      advantage in hearing in those frequencies. In addition, cave amblyopsids had
      lower hair cell densities compared with their surface relative. These traits may
      have evolved in response to the loud high-frequency background noise found in
      subterranean pools and streams. This study represents the first report of
      auditory regression in a subterranean organism.

PMID- 23536445
TI  - Experimental maturation of feathers: implications for reconstructions of fossil
      feather colour.
AB  - Fossil feathers often preserve evidence of melanosomes-micrometre-scale melanin
      bearing organelles that have been used to infer original colours and patterns of
      the plumage of dinosaurs. Such reconstructions acknowledge that evidence from
      other colour-producing mechanisms is presently elusive and assume that melanosome
      geometry is not altered during fossilization. Here, we provide the first test of
      this assumption, using high pressure-high temperature autoclave experiments on
      modern feathers to simulate the effects of burial on feather colour. Our
      experiments show that melanosomes are retained despite loss of visual evidence of
      colour and complete degradation of other colour-producing structures (e.g. quasi
      ordered arrays in barbs and the keratin cortex in barbules). Significantly,
      however, melanosome geometry and spatial distribution are altered by the effects
      of pressure and temperature. These results demonstrate that reconstructions of
      original plumage coloration in fossils where preserved features of melanosomes
      are affected by diagenesis should be treated with caution. Reconstructions of
      fossil feather colour require assessment of the extent of preservation of various
      colour-producing mechanisms, and, critically, the extent of alteration of
      melanosome geometry.

PMID- 23536446
TI  - From nitro- to sulfonyl-based chromophores: improvement of the comprehensive
      performance of nonlinear optical dendrimers.
AB  - Through the combination of the divergent and convergent approaches, coupled with
      the utilization of the powerful Sharpless "click-chemistry" reaction, two series
      of sulfonyl-based high-generation NLO dendrimers were conveniently prepared with
      high purity and in satisfactory yields. Thanks to the perfect three-dimensional
      (3D) spatial isolation from the highly branched structure and the isolation
      effect of the exterior benzene moieties and the interior triazole rings, these
      dendrimers exhibited large second harmonic generation coefficient (d33) values up
      to 181 pm V(-1), which, to the best of our knowledge, is the highest value so far
      for polymers containing sulfonyl-based chromophore moieties. Meanwhile, compared
      with the nitro-chromophore-based analogues, their optical transparency and NLO
      stability were improved in a large degree, due to the lower dipole moment (MU)
      and the special main-chain structure of sulfonyl-based chromophore in these
      dendrimers.

PMID- 23536447
TI  - Suramin attenuates dystrophin-deficient cardiomyopathy in the mdx mouse model of
      duchenne muscular dystrophy.
AB  - INTRODUCTION: The purpose of this study was to determine the effects of suramin,
      an antifibrotic agent, on cardiac function and remodeling in mdx mice. METHODS:
      mdx mice (8 months old) received intraperitoneal injections of suramin twice a
      week for 3 months. Control mdx mice (8 months old) were injected with saline.
      RESULTS: Suramin improved the electrocardiography profile with the main
      corrections seen in S- to R-wave ratio, PR interval, and Q amplitude, and a
      significant decrease in the cardiomyopathy index. Suramin decreased myocardial
      fibrosis, inflammation, and myonecrosis. CONCLUSIONS: These findings suggest that
      suramin may be a new adjunctive therapy to help improve cardiomyopathy in DMD.

PMID- 23536449
TI  - Atrial Fibrillation with Rapid Ventricular Response following use of Dietary
      Supplement Containing 1,3 Dimethylamylamine and Caffeine.
AB  - Our nation?s servicemembers commonly use dietary supplements to enhance their
      performance. Despite this prolific use, many of these products have detrimental
      side-effects that compromise servicemembers? health and could, by proxy,
      compromise a mission. This paper presents the case of a 32-year old Navy Special
      Operations Forces (SOF) Sailor who, prior to physical training, used a supplement
      containing 1,3 Dimethylamylamine (DMAA), and then developed atrial fibrillation
      with rapid ventricular response. He required intravenous calcium channel blocker
      administration, followed by beta blockers, for rate control. As military
      providers, we routinely ask our patients about their use of supplements and while
      the regulation of these products is beyond the scope of practice for most of us,
      it is our duty to become better educated about the risks and benefits of these
      supplements. We must educate our patients and our commands on the potential harm
      that these supplements may pose.

PMID- 23536448
TI  - Nucleophosmin 1, upregulated in adenomas and cancers of the colon, inhibits p53
      mediated cellular senescence.
AB  - Dysregulation of nucleophosmin 1 (NPM1) has been found in numerous solid and
      hematological malignancies. Our previous meta-analysis of colorectal cancer (CRC)
      high throughput gene expression profiling studies identified it as a consistently
      reported up-regulated gene in the malignant state. Our aims were to compare NPM1
      expression in normal colon, adenoma and CRC, to correlate their expressions with
      clinico-pathological parameters, and to assess the biological role of aberrant
      NPM1 expression in CRC cells. NPM1 transcript levels were studied in human CRC
      cell lines, whereas a tissue microarray of 57 normal human colon, 40 adenoma and
      185 CRC samples were used to analyze NPM1 protein expression by
      immunohistochemistry. CRC cell lines were subjected to transient siRNA-mediated
      knockdown to study NPM1's roles on cell viability and senescence. NPM1 transcript
      levels were 7-11-folds higher in three different human CRC cell lines compared to
      normal colon cells. NPM1 protein expression was found to be progressively and
      significantly upregulated in CRC compared to adenomas and in adenomas compared to
      normal mucosa. Reducing NPM1 expression by siRNA had caused a significant
      decrease in cell viability, a concomitant increase in cellular senescence and
      cell cycle arrest. Cellular senescence induced under conditions of forced NPM1
      suppression could be prevented by knocking down p53. The differential expression
      of NPM1 along the normal colon-adenoma-carcinoma progression and its involvement
      in resisting p53 related senescent growth arrest in CRC cell lines implicate its
      role in supporting CRC tumorigenesis. 

PMID- 23536450
TI  - Case series of pectoralis major muscle tears in joint special operations task
      force-Philippines soldiers diagnosed by bedside ultrasound.
AB  - Pectoralis major muscle tears are an uncommon injury although reported most
      prevalently among young male athletes (e.g. SOF personnel). We describe two cases
      occurring in Joint Special Operations Task Force-Philippines (JSOTF-P) Soldiers,
      review the physical examination and sonographic findings suggestive of a high
      grade injury, and discuss treatment options.

PMID- 23536451
TI  - Global health language and culture competency.
AB  - This article presents findings from a survey conducted to examine the
      availability of foreign language and culture training to Civil Affairs health
      personnel and the relevance of that training to the tasks they perform. Civil
      Affairs forces recognize the value of cross-cultural communication competence
      because their missions involve a significant level of interaction with foreign
      governments? officials, military, and civilians. Members of the 95th Civil
      Affairs Brigade (Airborne) who had a health-related military occupational
      specialty code were invited to participate in the survey. More than 45% of those
      surveyed were foreign language qualified. Many also received predeployment
      language and culture training specific to the area of deployment. Significantly
      more respondents reported receiving cultural training and training on how to work
      effectively with interpreters than having received foreign language training.
      Respondents perceived interpreters as important assets and were generally
      satisfied with their performance. Findings from the survey highlight a need to
      identify standard requirements for predeployment language training that focuses
      on medical and health terminology and to determine the best delivery platform(s).
      Civil Affairs health personnel would benefit from additional cultural training
      that focuses on health and healthcare in the country or region of deployment.
      Investing in the development of distance learning capabilities as a platform for
      delivering health-specific language and culture training may help ease the time
      and resources constraints that limit the ability of Civil Affairs health
      personnel to access the training they need.

PMID- 23536452
TI  - A novel cryotherapy compression wrap in the management of acute ankle sprains:
      potential use for special operators on the battlefield.
AB  - OBJECTIVE: Musculoskeletal injuries related to training and operational missions
      frequently affect military personnel. A common treatment for these injuries is
      the PRICE (protection, rest, ice, compression, and elevation) method, which is
      time consuming and impractical in the field. Therefore, the primary objective of
      this study was to determine the effectiveness of the cryotherapy wrap compared to
      a traditional treatment in the management of acute ankle sprains. METHODS: A
      randomized controlled clinical trial was conducted in a university research
      laboratory with 13 subjects (9 males and 4 females) with the following physical
      characteristics: age (yr) 20.6 ? 2.2, height (cm) 177.0 ? 14.3, weight (kg) 76.6
      ? 20.6, and body mass index (kg/m2) 24.1 ? 3.7. Participants were instructed to
      perform PRICE with a traditional ice pack and compression wrap (control group) or
      with an Arctic Ease? cryotherapy wrap (test group) for 48 hours following
      enrollment in the study. The Numeric Pain Scale, Foot and Ankle Ability Measure,
      and ankle/foot volumetric measurement were performed at initial presentation and
      24-hour, 48-hour, and 7-day follow-up intervals. RESULTS: While the comparison of
      the Numeric Pain Scale scores, Foot and Ankle Ability Measure scores, and
      volumetric changes between groups revealed no statistically significant
      differences (p > 0.01), there was an 86% compliance rate for subjects in the
      cryotherapy wrap group compared to a 17% compliance rate of subjects in the
      control group. CONCLUSIONS: The cryotherapy wraps performed comparably to ice
      therapy and therefore may be especially applicable to military personnel required
      to operate in austere and hostile environments where traditional therapies are
      unrealistic. Although this pilot study did not demonstrate that the cryotherapy
      wraps produce statistically superior results, trends emerged in the data
      suggesting that subject compliance rate may be improved by using an alternative
      form of cryotherapy compression, which could lead to better management of pain,
      edema, and functional recovery. Future research should include a larger sample
      size to verify this claim.

PMID- 23536453
TI  - Biofeedback self-regulation training to treat post-concussion headache in a
      special operations support soldier.
AB  - Biofeedback assisted self-regulation training can be an effective treatment for
      post-concussion headaches. The following is an example of using biofeedback
      assisted self-regulation training as an intervention to treat posttrauma
      headaches in a Special Operations Forces (SOF) support soldier. This Soldier was
      a 23-year-old male who had suffered a concussion while off duty four months
      earlier and continued to experience headache. Threemodality biofeedback
      (temperature, surface electromyogram and skin conduction) was used to help the
      patient learn to self-regulate and control his headaches. This was accomplished
      over four visits over two weeks. This was a compressed timeline to allow him to
      deploy with his unit. This form of treatment can be a viable nonmedication based
      option for addressing post concussion headaches for deploying Soldiers.

PMID- 23536454
TI  - Biometrics in support of special forces medical operations.
AB  - Recommendations on ways in which the ODA can leverage biometrics in medical
      operations to improve their security, improve relations with indigenous
      personnel, and contribute to the larger theater biometrics program.

PMID- 23536455
TI  - Forward assessment of 79 prehospital battlefield tourniquets used in the current
      war.
AB  - INTRODUCTION: Battlefield tourniquet use can be lifesaving, but most reports are
      from hospitals with knowledge gaps remaining at the forward surgical team (FST).
      The quality of tourniquet applications in forward settings remain unknown. The
      purpose of this case series is to describe observations of tourniquet use at an
      FST in order to improve clinical performance. METHODS: War casualties with
      tourniquet use presenting to an FST in Afghanistan in 2011 were observed. We
      identified appliers by training, device effectiveness, injury pattern, and
      clinical opportunities for improvement. Feedback was given to treating medics.
      RESULTS: Tourniquet applications (79) were performed by special operations combat
      medics (47, 59%), flight medics (17, 22%), combat medics (12, 15%), and general
      surgeons (3, 4%). Most tourniquets were Combat Application Tourniquets (71/79,
      90%). With tourniquets in place upon arrival at the FST, most limbs (83%, 54/65)
      had palpable distal pulses present; 17% were pulseless (11/65). Of all
      tourniquets, the use was venous in 83% and arterial in 17%. In total, there were
      14 arterial injuries, but only 5 had effective arterial tourniquets applied.
      DISCUSSION: Tourniquets are liberally applied to extremity injuries on the
      battlefield. 17% were arterial and 83% were venous tourniquets. When ongoing
      bleeding or distal pulses were appreciated, medics tightened tourniquets under
      surgeon supervision until distal pulses stopped. Medics were generally surprised
      at how tight a tourniquet must be to stop arterial flow ? convert a venous
      tourniquet into an arterial tourniquet. Implications for sustainment training
      should be considered with regard to this life-saving skill.

PMID- 23536456
TI  - Addressing maternal healthcare needs in the counterinsurgency environment.
AB  - All pregnant women are at risk of obstetric complications, most of which occur
      during labor and delivery among women with no previously identified risk factors.
      More than 95 percent of these deaths occur in developing countries. In sub
      Saharan Africa, a region of the world currently experiencing significant
      humanitarian crises, the lifetime risk of maternal death is one in 30 whereas the
      lifetime risk in developed countries is one in 2,800.1 The majority of maternal
      deaths from obstetric complications are due to hemorrhage, eclampsia, sepsis, or
      obstructed labor, each of which is treatable. Emergency obstetric care is
      critical to reducing maternal death and disability. SOF medical personnel
      supporting counterinsurgency (COIN) operations may find themselves in situations
      where no legitimate agencies are available to provide maternal healthcare.
      Similarly, SOF medical personnel should be prepared to assist in rebuilding
      infrastructure and basic services to include the provision for maternal health.
      This article provides an overview of maternal health in underdeveloped countries;
      the importance of addressing the unique healthcare needs of women during COIN
      operations; and how the employment of Female Treatment Teams (FTT) can assist in
      meeting these needs. A subsequent article will review the basics of prenatal care
      and life-saving emergency obstetric care, and discusses the essential information
      and skills that should be taught in a MEDSEM covering maternal healthcare.

PMID- 23536457
TI  - Intensive skills week for military medical students increases technical
      proficiency, confidence, and skills to minimize negative stress.
AB  - The effects of stress induced cortisol on learning and memory is well documented
      in the literature.1-3 Memory and learning are enhanced at low levels while high
      levels are detrimental. Repetitive training in stressful situations enables
      management of the stress response4 as demonstrated by the high intensity training
      military members undergo to prepare for tactical situations. Appropriate
      management of one?s stress response is critical in the medical field, as the
      negative effects of stress can potentially hinder life-saving procedures and
      treatments. This also applies to physicians-in-training as they learn and
      practice triage, emergency medicine, and surgical skills prior to graduation.
      Rocky Vista University?s Military Medicine Honor?s Track (MMHT) held a week long
      high-intensity emergency medicine and surgical Intensive Skills Week (ISW),
      facilitated by military and university physicians, to advance students? skills
      and maximize training using the Human Worn Partial Surgical Task Simulator (Cut
      Suit). The short-term goal of the ISW was to overcome negative stress responses
      to increase confidence, technical and non-technical knowledge, and skill in
      surgery and emergency medicine in an effort to improve performance as third-year
      medical students. The long-term goal was to enhance performance and proficiency
      in residency and future medical practice. The metrics for the short-term goals
      were the focus of this pilot study. Results show an increase in confidence and
      decrease in perceived stress as well as statistically significant improvements in
      technical and non-technical skills and surgical instrumentation knowledge
      throughout the week. There is a correlative benefit to physician and non
      physician military personnel, especially Special Operations Forces (SOF) medical
      personnel, from developing and implementing similar training programs when live
      tissue or cadaver models are unavailable or unfeasible.

PMID- 23536458
TI  - Resourcing interventions enhance psychology support capabilities in special
      operations forces.
AB  - This study provides an examination of approaches to United States Government
      (USG) resourcing interventions on a national scale that enhance psychology
      support capabilities in the Special Operations Forces (SOF) community. A review
      of Congressional legislation and resourcing trends in the form of authorizations
      and appropriations since 2006 demonstrates how Congress supported enhanced
      psychology support capabilities throughout the Armed Forces and in SOF supporting
      innovative command interests that address adverse affects of operations tempo
      behavioral effects (OTBE). The formulation of meaningful metrics to address SOF
      specific command interests led to a personnel tempo (PERSTEMPO) analysis in
      response to findings compiled by the Preservation of the Force and Families
      (POTFF) Task Force. The review of PERSTEMPO data at subordinate command and unit
      levels enhances the capability of SOF leaders to develop policy and guidance on
      training and operational planning that mitigates OTBE and maximizes resourcing
      authorizations. A major challenge faced by the DoD is in providing behavioral
      healthcare that meets public and legislative demands while proving suitable and
      sustainable at all levels of military operations: strategic, operational, and
      tactical. Current legislative authorizations offer a mechanism of command
      advocacy for resourced multi-functional program development that enhances
      psychology support capabilities while reinforcing SOF readiness and performance.

PMID- 23536459
TI  - War time medicine on a peace time mission.
AB  - As we realized the MEDEVAC from JTF-B was not going to happen, the words of
      instructors from the Joint Special Operations Medical Training Center (JSOMTC)
      echoed through my head, ?Men, pay attention to this. There will be a day when
      you, as Deltas, will have to sustain a patient for hours, possibly days; this is
      what separates you from any other medical professional in the military, so shut
      up and stay awake.? We had heard those words every time we started a new section
      of Special Forces Medical Sergeants (SFMS) course. Now those words were staring
      right back at us in the form of the patient?s friends and family. We looked at
      our patient in the back of that beat up truck and knew we could keep our patient
      alive. We had the knowledge and the equipment; we just didn?t know how much
      longer we would have to sustain him.

PMID- 23536460
TI  - Combat ready clamp medic technique.
AB  - BACKGROUND: Junctional hemorrhage control device use on the battlefield might be
      lifesaving, but little experience is reported. The purpose of the present case
      report is to detail prehospital use of the Combat Ready Clamp (called the CRoC by
      its users, Combat Medical Systems, Fayetteville, NC; Instructions for Use, 2010)
      in casualty care in order to increase awareness of junctional hemorrhage control.
      METHODS: The CRoC was used to control difficult inguinal bleeding on the
      battlefield for an Afghani man with a hindquarter traumatic amputation. RESULTS:
      The device promptly controlled exsanguination from a critical injury when placed
      during rotary-wing casualty evacuation. The flight medic applied the device in 90
      seconds. The device performed well without complications to control bleeding.
      DISCUSSION: The CRoC, a new junctional hemorrhage control device, was used as
      indicated on the battlefield with mechanical and physiologic success and without
      device problems. By controlling difficult inguinal bleeding resulting from
      battlefield trauma, the device facilitated casualty stabilization and delivery to
      a surgical facility. The device facilitated the ability of a new flight medic to
      focus his expertise on a critically injured battlefield casualty with
      demonstrable success.

PMID- 23536461
TI  - USSOCOM TCCC CASEVAC Set Program A Retrospective and Overview.
AB  - The United States Special Operations Command (USSOCOM) Tactical Combat Casualty
      Care (TCCC) Casualty Evacuation (CASEVAC) Set Program was initiated in 2006 as a
      three-step effort. The initial effort was to develop an improved Individual First
      Aid Kit (IFAK); this was followed by the development of a Medic bag and
      culminated with the CASEVAC Set. The intent of the Program is both standardizing
      the medical load out across SOF components and expanding the skill set of Special
      Operations Forces (SOF) medical practitioners by providing equipment and training
      outside the normal parameters of many units. Even though the Set is currently
      being fielded to a variety of units, there are still personnel unaware of the Set
      and its capabilities. The goal of this article is to increase awareness of the
      existence of the program and to promote thought/discussion regarding the
      expansion of the capabilities of the Advanced Tactical Practitioner (ATP) beyond
      traditional medical skills. This program is best understood by first looking back
      to where it originated, and then examining where it is at present.

PMID- 23536462
TI  - Redefining Technical Rescue and Casualty Care for SOF: Part 1.
AB  - Trauma care in the tactical environment is complex; it requires a unique blend of
      situational awareness, foresight, medical skill, multitasking, and physical
      strength. Rescue is a critical, but often over-looked, component of nearly all
      tactical trauma casualty management. Successful full spectrum casualty management
      requires proficiency in four areas: casualty access, assessment, stabilization,
      and extraction. When complex rescue situations arise (casualty removal from roof
      tops, mountain terrain, collapsed structures, wells, or a karez), casualty care
      often becomes further complicated. Special Operations units have historically
      looked to civilian technical rescue techniques and equipment to fill this ?rescue
      gap.? Similar to the evolution of pre-hospital military medicine from civilian
      guidelines (e.g. Advanced Trauma Life Support) (ATLS)) to an evidence-based,
      tactical-specific guideline (Tactical Combat Casualty Care (TCCC)), an evolution
      is required within the rescue paradigm. This shift from civilian-based technical
      rescue guidelines towards an Operational Rescue? capability allows tactical
      variables such as minimal equipment, low light/night vision goggles (NVG)
      considerations, enemy threats, and variable evacuation times to permeate through
      the individual rescue skill set. Just as with TCCC, in which the principles of
      casualty care remain consistent, the practices must be adapted to end-users
      environment, so it is with rescue.

PMID- 23536463
TI  - An oil-based formulation of Isaria fumosorosea blastospores for management of
      greenhouse whitefly Trialeurodes vaporariorum (Homoptera: Aleyrodidae).
AB  - BACKGROUND: To date, emphasis has been placed on studying the virulence of Isaria
      fumosorosea conidia rather than the virulence of their blastospores. In the
      present study, a comparison was made of the efficacy of blastospores of I.
      fumosorosea (SFP-198) versus conidia against greenhouse whitefly (GWF)
      Trialeurodes vaporarioum nymphs and thermotolerance at 50  degrees C. To improve
      thermotolerance and potency, the blastospores were suspended in corn oil with a
      wetting and an insect-filming agent. RESULTS: Blastospores had similar efficacy
      against GWF nymphs to conidia in glasshouse conditions but had less
      thermotolerance than conidia. However, blastospores in corn oil had increased
      thermotolerance, comparable with that of conidia in corn oil. Application of SFP
      198 blastospore oil-based formulation containing isotridecyl alcohol ethoxylated
      3EO (TDE-3) and sodium alginate (SA) as adjuvants showed enhanced efficacy (95.7%
      mortality), compared with the SA-free oil formulation (72.8%) in 10 days.
      CONCLUSION: SFP-198 blastospores can be used as an effective biological control
      agent, given their virulence against GWF, the enhanced thermotolerance in corn
      oil and the oil-based formulation studies to enhance their efficacy. Blastospores
      can be easily produced in liquid cultures in less than 4 days, which is
      significantly shorter than using traditional solid cultures for conidial
      production.

PMID- 23536464
TI  - Speech disorders from Parkinson's disease: try to sing it! A case report.

PMID- 23536465
TI  - Screening athletes for cardiovascular disease in Africa: a challenging
      experience.
AB  - AIMS: Preparticipation cardiovascular (CV) screening has been advocated as an
      efficient strategy to reduce sudden cardiac death in Caucasian athletes. At
      present, uncertainty remains if such strategy is feasible and efficient in native
      African athletes. To this scope, we performed a CV screening in an African
      setting. METHODS: 210 male Gabonian football players were examined with history,
      physical examination, ECG and echocardiography. RESULTS: On history, 19 players
      (9%) referred atypical chest discomfort/oppression. Familial sudden death was
      referred by 36 (17%). No anomalies were detected at physical examination. ECG
      showed large proportions of 'training-related' abnormalities, that is, ST-segment
      elevation in precordial leads in 150 (71.4%), and isolated increase in R/S-wave
      voltage in 116 (55.2%). A substantial subset (12.4%) showed 'training-unrelated'
      abnormalities, that is, inverted T-waves in 10 (4.8%), left atrial enlargement in
      8 (4%), deep Q-waves in 3 (1.4%). On echocardiography, one athlete meet criteria
      for hypertrophic cardiomyopathy (HCM); none showed evidence for arrhythmogenic
      right ventricular cardiomyopathy (ARVC) or dilated cardiomyopathy (DCM). Other
      abnormalities included mitral valve prolapse in three, atrial septal defect in
      two and pulmonary hypertension in one. CONCLUSIONS: About 12% of native African
      athletes showed ECG abnormalities unrelated to training and requiring additional
      testing and periodical follow-up. Structural abnormalities were found, however,
      in a minority (5%), including HCM in one, but no ARVC or DCM. In conclusion, this
      study demonstrates that preparticipation CV screening is efficient to identify
      (or raise suspicion) for CV abnormalities in native African athletes, but
      challenging for conclusive identification of cardiac diseases in the difficult
      scenario of a developing African country.

PMID- 23536466
TI  - Acute hamstring injuries in Swedish elite football: a prospective randomised
      controlled clinical trial comparing two rehabilitation protocols.
AB  - BACKGROUND: Hamstring injury is the single most common injury in European
      professional football and, therefore, time to return and secondary prevention are
      of particular concern. OBJECTIVE: To compare the effectiveness of two
      rehabilitation protocols after acute hamstring injury in Swedish elite football
      players by evaluating time needed to return to full participation in football
      team-training and availability for match selection. STUDY DESIGN: Prospective
      randomised comparison of two rehabilitation protocols. METHODS: Seventy-five
      football players with an acute hamstring injury, verified by MRI, were randomly
      assigned to one of two rehabilitation protocols. Thirty-seven players were
      assigned to a protocol emphasising lengthening exercises, L-protocol and 38
      players to a protocol consisting of conventional exercises, C-protocol. The
      outcome measure was the number of days to return to full-team training and
      availability for match selection. Reinjuries were registered during a period of
      12 months after return. RESULTS: Time to return was significantly shorter for the
      players in the L-protocol, mean 28 days (1SD+/-15, range 8-58 days), compared
      with the C-protocol, mean 51 days (1SD+/-21, range 12-94 days). Irrespective of
      protocol, stretching-type of hamstring injury took significantly longer time to
      return than sprinting-type, L-protocol: mean 43 vs 23 days and C-protocol: mean
      74 vs 41 days, respectively. The L-protocol was significantly more effective than
      the C-protocol in both injury types. One reinjury was registered, in the C
      protocol. CONCLUSIONS: A rehabilitation protocol emphasising lengthening type of
      exercises is more effective than a protocol containing conventional exercises in
      promoting time to return in Swedish elite football.

PMID- 23536467
TI  - Total synthesis and biological evaluation of grassypeptolide A.
AB  - Herein, we describe in full our investigations into the synthesis of
      grassypeptolide A (1) in 17 linear steps with an overall yield of 11.3 %. In
      particular, this work features the late-stage introduction of sensitive
      bis(thiazoline) heterocycles and 31-membered macrocyclization conducted at the
      sterically congested secondary amide site in superb conversion (72 % yield).
      Biological evaluation indicated that grassypeptolide A significantly inhibited
      cancer cell proliferation in a dose-dependent manner. It induced cancer cell
      apoptosis, which was associated with increased cleavage of poly(ADP-ribose)
      polymerase (PARP) and decreased expression of bcl-2 and bcl-xL. Furthermore,
      grassypeptolide A also caused cell cycle redistribution by increasing cells in
      the G1 phase and decreasing cells in the S and G2 phases. In addition, cell cycle
      arrest was correlated with downregulation of cyclin D and upregulation of p27 and
      p21.

PMID- 23536468
TI  - Response to Impact of lesion length on functional significance in intermediate
      coronary lesions.

PMID- 23536469
TI  - Physician accountability in iatrogenic cerebrospinal fluid leak litigation.
AB  - BACKGROUND: The potentially severe complications resulting from cerebrospinal
      fluid (CSF) leak makes iatrogenic injury a medicolegal area of concern for
      otolaryngologists and neurosurgeons. The objectives of this analysis were to
      study legal outcomes as well as medical and nonmedical elements affecting
      malpractice litigation. METHODS: Public court records available in the Westlaw
      legal database (Thomson Reuters, New York, NY) were searched for medical
      malpractice litigation related to iatrogenic CSF leak. Of the 18 jury verdicts
      and settlements included, outcomes and awards, patient demographic data, and
      other factors instrumental in determining legal responsibility were recorded for
      comparison. RESULTS: Ten (55.6%) cases were resolved in the defendant's favor, 2
      (11.1%) resulted in damages awarded by a jury, and 6 (33.3%) were settled out of
      court before resolution of trial. Mean damages awarded were $1.1 million, while
      out of court settlements averaged $966,887. Malpractice stemming from patients
      who underwent endoscopic sinus surgery comprised 77.8% of cases analyzed. The
      most frequent alleged factors cited for litigation included having to undergo
      additional surgery (88.9%), developing meningitis (50.0%), and failing to
      recognize complications in a timely manner (44.4%). Perceived deficits in
      informed consent were alleged in one-third of cases. CONCLUSION: Although a
      slight majority of cases were resolved in the defendant's favor, payments made
      were considerable, averaging approximately $1 million. Strategies to decrease
      liability and allow patients to make more informed decisions should include clear
      communication with patients that explicitly states potential risks, such as
      meningitis, and possible need to undergo additional reparative surgery.

PMID- 23536470
TI  - Efficacy of sulfuryl fluoride against the pinewood nematode, Bursaphelenchus
      xylophilus (Nematoda: Aphelenchidae), in Pinus pinaster boards.
AB  - BACKGROUND: The pinewood nematode (PWN) Bursaphelenchus xylophilus is an
      important conifer disease worldwide. It is the direct cause of the death of
      millions of pines in south-east Asia (mainly Japan, China and Korea) and has been
      established in Portugal since 1999. The phasing out of methyl bromide has created
      an urgent need for alternative treatment of wood packaging materials. The effect
      of sulfuryl fluoride (SF), a broad-spectrum fumigant used to control insects, was
      tested in Pinus pinaster boards naturally infested by PWN. RESULTS: Boards were
      fumigated for 24 h at three different temperatures (15, 20 and 30  degrees C)
      with dosage ranges of 3169-4407, 1901-4051 and 1385-2141 gh m(-3) respectively.
      Treated wood was sampled for nematode identification and counting, before
      treatment and after 24 h, 72 h and 21 days. No survival was found in the 15 
      degrees C and 30  degrees C treatments, while at 20  degrees C the mortality
      ranged from 94.06 to 100%. Some reasons for the survival at 20  degrees C are
      presented. CONCLUSION: Results confirm SF to be an effective quarantine treatment
      for PWN at 15 and 30  degrees C. Further studies are needed to obtain the most
      effective dosage at 20  degrees C, and to determine the toxicity of SF fumigation
      on B. xylophilus at other temperatures, especially at 25  degrees C.

PMID- 23536471
TI  - Plasma urate in REM sleep behavior disorder.
AB  - BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is associated
      with a high risk of developing Parkinson's disease (PD). Higher urate levels are
      associated with a lower risk of PD. We conducted a study to evaluate plasma urate
      levels in patients with RBD and their role in the development of PD. METHODS: We
      evaluated plasma urate levels in a cohort of 24 patients with idiopathic RBD.
      Patients were divided into 2 groups according to the presence or absence of PD.
      Other known markers of the risk of developing PD, such as olfaction testing, and
      substantia nigra (SN) hyperechogenicity, were evaluated in the 2 groups. RESULTS:
      No differences were observed regarding age, years of evolution of the RBD, SN
      hyperechogenicity, or plasma urate levels between the 2 groups. In patients
      without PD, there was a positive correlation between years of evolution of RBD
      and the levels of uric acid (R(2)  =0.88). Patients without PD and those who had
      more than 5 years of RBD exhibited higher levels of uric acid than patients with
      PD (P=0.02). CONCLUSIONS: Higher levels of plasma urate were associated with a
      longer duration of RBD without converting to PD. Future prospective studies would
      be needed to confirm this finding. Disorder Society

PMID- 23536472
TI  - Fabrication of magnetic yolk-shell nanocatalysts with spatially resolved
      functionalities and high activity for nitrobenzene hydrogenation.
AB  - In cracking from: Highly engineered bifunctional yolk-shell nanocatalysts with
      tailored structural configuration, that is, hollow carbon spheres as the matrix,
      entrapped magnetite nanoparticles in the core, and in situ formed and highly
      dispersed noble metal nanoparticles within the carbon shells as active catalytic
      sites, were prepared. These nanocatalysts show high activity, reusability, and
      good magnetic separation properties.

PMID- 23536473
TI  - Necrosis in DU145 prostate cancer spheroids induces COX-2/mPGES-1-derived PGE2 to
      promote tumor growth and to inhibit T cell activation.
AB  - Cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2 ) supports the growth of a
      spectrum of cancers. The potential benefit of COX-2-inhibiting non-steroidal anti
      inflammatory drugs (NSAIDs) for cancer treatment is however limited by their well
      known cardiovascular side-effects. Therefore, targeting microsomal PGE synthase 1
      (mPGES-1), the downstream enzyme in the COX-2-dependent pathway of PGE2
      production might be attractive, although conflicting data regarding a potential
      tumor-supporting function of mPGES-1 were reported. We determined the impact of
      mPGES-1 in human DU145 prostate cancer cell growth. Surprisingly, knockdown of
      mPGES-1 did not alter growth of DU145 monolayer cells, but efficiently inhibited
      the growth of DU145 multicellular tumor spheroids (MCTS). Opposed to MCTS,
      monolayer cells did not secrete PGE2 due to a lack of COX-2 expression, which was
      induced during spheroid formation. Pharmacological inhibition of COX-2 and mPGES
      1 supported the crucial role of PGE2 for growth of MCTS. The functionality of
      spheroid-derived PGE2 was demonstrated by its ability to inhibit cytotoxic T cell
      activation. When investigating mechanisms of spheroid-induced COX-2 induction, we
      observed that among microenvironmental factors neither glucose deprivation,
      hypoxia nor tumor cell apoptosis enhanced COX-2 expression. Interestingly,
      interfering with apoptosis in spheroids triggered a shift towards necrosis, thus
      augmenting COX-2 expression. We went on to demonstrate that necrotic cells
      induced COX-2 mRNA expression and PGE2 secretion from live tumor cells. In
      conclusion, necrosis-dependent COX-2 upregulation in MCTS promoted PGE2 
      dependent tumor growth and inhibited activated cytotoxic T cells. Hence, blocking
      mPGES-1 as a therapeutic option may be considered for COX-2/mPGES-1-positive
      solid cancers. 

PMID- 23536475
TI  - Huntington's disease gene expansion associates with early onset nonprogressive
      chorea.

PMID- 23536474
TI  - Regulation of cholesterol and bile acid homeostasis by the cholesterol 7alpha
      hydroxylase/steroid response element-binding protein 2/microRNA-33a axis in mice.
AB  - Bile acid synthesis not only produces physiological detergents required for
      intestinal nutrient absorption, but also plays a critical role in regulating
      hepatic and whole-body metabolic homeostasis. We recently reported that
      overexpression of cholesterol 7alpha-hydroxylase (CYP7A1) in the liver resulted
      in improved metabolic homeostasis in Cyp7a1 transgenic (Cyp7a1-tg) mice. This
      study further investigated the molecular links between bile acid metabolism and
      lipid homeostasis. Microarray gene profiling revealed that CYP7A1 overexpression
      led to marked activation of the steroid response element-binding protein 2
      (SREBP2)-regulated cholesterol metabolic network and absence of bile acid
      repression of lipogenic gene expression in livers of Cyp7a1-tg mice.
      Interestingly, Cyp7a1-tg mice showed significantly elevated hepatic cholesterol
      synthesis rates, but reduced hepatic fatty acid synthesis rates, which was
      accompanied by increased (14) C-glucose-derived acetyl-coenzyme A incorporation
      into sterols for fecal excretion. Induction of SREBP2 also coinduces intronic
      microRNA-33a (miR-33a) in the SREBP2 gene in Cyp7a1-tg mice. Overexpression of
      miR-33a in the liver resulted in decreased bile acid pool, increased hepatic
      cholesterol content, and lowered serum cholesterol in mice. CONCLUSION: This
      study suggests that a CYP7A1/SREBP2/miR-33a axis plays a critical role in
      regulation of hepatic cholesterol, bile acid, and fatty acid synthesis.
      Antagonism of miR-33a may be a potential strategy to increase bile acid synthesis
      to maintain lipid homeostasis and prevent nonalcoholic fatty liver disease,
      diabetes, and obesity.

PMID- 23536477
TI  - Computational study on the attack of .OH radicals on aromatic amino acids.
AB  - The attack of hydroxyl radicals on aromatic amino acid side chains, namely
      phenylalanine, tyrosine, and tryptophan, have been studied by using density
      functional theory. Two reaction mechanisms were considered: 1) Addition reactions
      onto the aromatic ring atoms and 2) hydrogen abstraction from all of the possible
      atoms on the side chains. The thermodynamics and kinetics of the attack of a
      maximum of two hydroxyl radicals were studied, considering the effect of
      different protein environments at two different dielectric values (4 and 80). The
      obtained theoretical results explain how the radical attacks take place and
      provide new insight into the reasons for the experimentally observed preferential
      mechanism. These results indicate that, even though the attack of the first (.)OH
      radical on an aliphatic C atom is energetically favored, the larger
      delocalization and concomitant stabilization that are obtained by attack on the
      aromatic side chain prevail. Thus, the obtained theoretical results are in
      agreement with the experimental evidence that the aromatic side chain is the main
      target for radical attack and show that the first (.)OH radical is added onto the
      aromatic ring, whereas a second radical abstracts a hydrogen atom from the same
      position to obtain the oxidized product. Moreover, the results indicate that the
      reaction can be favored in the buried region of the protein.

PMID- 23536476
TI  - Comparison of endoscopically-guided swab vs aspirate culture techniques in post
      endoscopic sinus surgery patients: blinded, prospective analysis.
AB  - BACKGROUND: Culture-directed antibiotic therapy remains imperative in the
      management paradigm of chronic rhinosinusitis (CRS). The objective of this study
      was to conduct a prospective, blinded comparison of endoscopically-guided swab
      and aspirate cultures from the same sinonasal site in patients presenting with
      acute infectious exacerbations post-sinus surgery. METHODS: Forty-nine CRS
      patients were prospectively enrolled in a tertiary care rhinology clinic. At the
      conclusion of the study, all cultures were unblinded to determine mean culture
      yield, most common pathogens, potential contaminants, and therapeutic
      correlation. RESULTS: The mean patient age was 49 years and 40.8% were males. All
      patients had evidence of symptomatic exacerbation with purulence on endoscopy at
      the time of presentation. There was a mean of 1.367 pathogens assayed per
      aspirate culture vs a mean of 1.102 per swab culture (p = 0.0032). The prevalence
      of Pseudomonas aeruginosa was 42% for aspirate vs 30% for swab cultures,
      respectively. The prevalence of Staphylococcus aureus was 49% for suction
      cultures vs 45% for swab cultures. There were 9 and 11 likely contaminants using
      aspirate and swab cultures, respectively. Therapeutic correlation was strong in
      67%, moderate in 18%, and weak in 14% of patients. CONCLUSION: This prospective
      analysis demonstrated higher culture yield, particularly with Pseudomonas, with
      aspirate vs swab cultures in postoperative patients. There is a strong clinical
      correlation between the 2 methods, and both aspirate and swab techniques serve as
      acceptable alternatives for endoscopic-guided cultures in patients with post
      functional endoscopic sinus surgery infectious exacerbations.

PMID- 23536478
TI  - Variations in circulating sex steroid levels in metastatic prostate cancer
      patients with combined androgen blockade: observation and implication.
AB  - Testosterone is the major precursor of estradiol (E2) in men. We hypothesized
      that, in metastatic prostate cancer, androgen deprivation therapy suppression of
      serum androgen to the castration level may also disrupt serum E2 level, and
      variation in serum E2 level might play a role in the development of castration
      resistant prostate cancer. Our investigation was designed to observe the
      variation in circulating oestrogen and androgen levels in metastatic prostate
      cancer patients after combined androgen blockade, and to explore the possible
      clinical significance. We recruited 105 consecutive metastatic prostate cancer
      patients who were treated with combined androgen blockade from June to August
      2011, and divided them into three groups according to different hormone
      sensitivity status, including 58 hormone-sensitive prostate cancers, 27 after
      failure of first-line hormone therapy (androgen-independent prostate cancer) and
      20 castration-resistant prostate cancers. Another 36 consecutive patients with
      treatment-naive metastatic prostate cancer during the same period were used as
      controls. Serum testosterone, E2 and E2/testosterone (E2/T) ratio were analysed
      and compared between the groups. After combined androgen blockade, testosterone
      was suppressed to a low level, regardless of different hormone sensitivity (p >
      0.05). Mean serum testosterone was 4.07, 0.15, 0.11 and 0.09 ng/mL in treatment
      naive, hormone-sensitive, androgen-independent and castration-resistant prostate
      cancer respectively. For each group, mean E2 was 33.06, 9.23, 9.13 and 15.05
      pg/mL respectively. Mean E2/T was 9.58, 269.29, 292.06 and 996.67 respectively.
      Recovery of E2 and increased E2/T ratio were more significantly associated with
      combined androgen blockade failure, especially in castration-resistant prostate
      cancer (p < 0.001). This study indicated that metabolism of oestrogen might
      change during combined androgen blockade in metastatic prostate cancer patients,
      and oestrogen-related pathways might play a role in the development of castration
      resistant prostate cancer.

PMID- 23536480
TI  - A technique of endoscopic stapling of pharyngeal pouch for patients with limited
      mouth opening.

PMID- 23536479
TI  - Thermodynamic characterization of human telomere quadruplex unfolding.
AB  - The 3'-terminal extensions of eukaryotic chromosomes are unique examples of
      functional single-stranded DNA. Human telomeres are constructed of the repeated
      DNA sequence 5'-d(TTAGGG). Four-repeats of human telomeric DNA have been
      characterized by high-resolution techniques to be capable of forming at least
      five distinct monomeric conformations. The predominant solution topology is
      influenced by solution conditions and the presence of 3'- or 5'-flanking
      residues. This study describes the unfolding mechanisms for human telomeric
      quadruplexes formed by eight sequence variants that form three unique
      antiparallel topologies in K(+) solution. Thermal unfolding monitored by circular
      dichroism is analyzed by singular value decomposition to enumerate the number of
      significant spectral species required to model the unfolding process. Thermal
      denaturation of all quadruplexes studied is found to be best modeled by a four
      state sequential mechanism with two populated intermediates. The thermal
      unfolding was also investigated in 50% (v/v) acetonitrile in which a parallel
      topology is favored. Under these dehydrating conditions, quadruplex thermal
      denaturation is best modeled by a three-state sequential unfolding mechanism with
      one populated intermediate. Dehydrated parallel quadruplexes demonstrate
      increased thermal stability. The spectral properties of the unfolding
      intermediate suggest that it is most likely a triple-helical structure.

PMID- 23536481
TI  - Controlled click-assembly of well-defined hetero-bifunctional cubic
      silsesquioxanes and their application in targeted bioimaging.
AB  - A general procedure for the assembly of hetero-bifunctional cubic silsesquioxanes
      with diverse functionality and a perfectly controlled distribution of functional
      groups on the inorganic framework has been developed. The method is based on a
      two-step sequence of mono- and hepta-functionalization through the ligand
      accelerated copper(I)-catalyzed azide-alkyne cycloaddition of a readily available
      octaazido cubic silsesquioxane. The stoichiometry of the reactants and the law of
      binomial distribution essentially determine the selectivity of the key
      monofunctionalization reaction when a copper catalyst with strong donor ligands
      is used. The methodology has been applied to the preparation of a set of
      bifunctional nano-building-blocks with orthogonal reactivity for the controlled
      assembly of precisely defined hybrid nanomaterials and a fluorescent multivalent
      probe for application in targeted cell-imaging. The inorganic cage provides an
      improved photostability to the covalently attached dye as well as a convenient
      framework for the 3D multivalent display of the pendant epitopes. Thus,
      fluorescent bioprobes based on well-defined cubic silsesquioxanes offer
      interesting advantages over more conventional fully organic analogues and ill
      defined hybrid nanoparticles and promise to become powerful tools for the study
      of cell biology and for biomedical applications.

PMID- 23536482
TI  - Improving access to liver transplantation: another part of the puzzle.

PMID- 23536483
TI  - Prevention of de novo hepatitis B with adefovir plus vaccination in recipients of
      liver transplants from core antibody-positive donors.

PMID- 23536484
TI  - Discovery of naturally occurring transmissible chronic hepatitis B virus
      infection among Macaca fascicularis from Mauritius Island.
AB  - Despite a high prevalence of hepatitis B virus (HBV) infection in endangered
      apes, no HBV infection has been reported in small, old-world monkeys. In search
      for a small, nonhuman primate model, we investigated the prevalence of HBV
      infection in 260 macaque (Cercopithecidae) sera of various geographical origins
      (i.e., Morocco, Mauritius Island, and Asia). HBV-positive markers were detected
      in cynomolgus macaques (Macaca fascicularis) from Mauritius Island only, and,
      remarkably, HBV DNA was positive in 25.8% (31 of 120) and 42% (21 of 50) of serum
      and liver samples, respectively. Strong liver expression of hepatitis B surface
      antigen and hepatitis B core antigen was detected in approximately 20%-30% of
      hepatocytes. Furthermore, chronic infection with persisting HBV DNA was
      documented in all 6 infected macaques during an 8-month follow-up period. Whole
      HBV genome-sequencing data revealed that it was genotype D subtype ayw3 carrying
      substitution in position 67 of preS1. To confirm infectivity of this isolate, 3
      Macaca sylvanus were inoculated with a pool of M. fascicularis serum and
      developed an acute HBV infection with 100% sequence homology, compared with HBV
      inoculum. We demonstrated the presence of a chronic HBV infection in M.
      fascicularis from Mauritius Island. This closely human-related HBV might have
      been transmitted from humans, because the initial breeding colony originated from
      very few ancestors 300 years ago when it was implemented by Portuguese who
      imported a handful of macaques from Java to Mauritius Island. CONCLUSION: This
      report on natural, persisting HBV infection among cynomolgus macaques provides
      the first evidence for the existence of a novel, small simian model of chronic
      HBV infection, immunologically close to humans, that should be most valuable for
      the study of immunotherapeutic approaches against chronic hepatitis B.

PMID- 23536485
TI  - Optimal time interval between neoadjuvant chemoradiotherapy and surgery for
      rectal cancer.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) has been proven to increase local
      control in rectal cancer, but the optimal interval between CRT and surgery is
      still unclear. The purpose of this study was to analyse the influence of
      variations in clinical practice regarding timing of surgery on pathological
      response at a population level. METHODS: All evaluable patients who underwent
      preoperative CRT for rectal cancer between 2009 and 2011 were selected from the
      Dutch Surgical Colorectal Audit. The interval between radiotherapy and surgery
      was calculated from the start of radiotherapy. The primary endpoint was
      pathological complete response (pCR; pathological status after chemoradiotherapy
      (yp) T0 N0). RESULTS: A total of 1593 patients were included. The median interval
      between radiotherapy and surgery was 14 (range 6-85, interquartile range 12-16)
      weeks. Outcome measures were calculated for intervals of less than 13 weeks (312
      patients), 13-14 weeks (511 patients), 15-16 weeks (406 patients) and more than
      16 weeks (364 patients). Age, tumour location and R0 resection rate were
      distributed equally between the four groups; significant differences were found
      for clinical tumour category (cT4: 17.3, 18.4, 24.5 and 26.6 per cent
      respectively; P = 0.010) and clinical metastasis category (cM1: 4.4, 4.8, 8.9 and
      14.9 per cent respectively; P < 0.001). Resection 15-16 weeks after the start of
      CRT resulted in the highest pCR rate (18.0 per cent; P = 0.013), with an
      independent association (hazard ratio 1.63, 95 per cent confidence interval 1.20
      to 2.23). Results for secondary endpoints in the group with an interval of 15-16
      weeks were: tumour downstaging, 55.2 per cent (P = 0.165); nodal downstaging,
      58.6 per cent (P = 0.036); and (near)-complete response, 23.2 per cent (P =
      0.124). CONCLUSION: Delaying surgery until the 15th or 16th week after the start
      of CRT (10-11 weeks from the end of CRT) seemed to result in the highest chance
      of a pCR.

PMID- 23536487
TI  - In situ deprotection and incorporation of unnatural amino acids during cell-free
      protein synthesis.
AB  - The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis
      removes a wide range of alpha-amino acid protecting groups by cleaving alpha
      carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl
      and adamantyl carboxamides; alpha-amino form-, acet-, trifluoroacet-, and
      benzamides; and side-chain hydrazides and esters. The free amino acids are
      produced and incorporated into a protein under standard conditions. This approach
      allows the deprotection of amino acids to be carried out in situ to avoid
      separate processing steps. The advantages of this approach are demonstrated by
      the efficient incorporation of the chemically intractable (S)-4-fluoroleucine,
      (S)-4,5-dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the
      direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide,
      (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These
      results also show that the fluoro- and dehydroleucine and the chlorovaline are
      incorporated into a protein by the normal biosynthetic machinery as substitutes
      for leucine and isoleucine, respectively.

PMID- 23536486
TI  - Loss of interneuron LTD and attenuated pyramidal cell LTP in Trpv1 and Trpv3 KO
      mice.
AB  - TRPV (transient receptor potential, vanilloid) channels are a family of
      nonselective cation channels that are activated by a wide variety of chemical and
      physical stimuli. TRPV1 channels are highly expressed in sensory neurons in the
      peripheral nervous system. However, a number of studies have also reported TRPV
      channels in the brain, though their functions are less well understood. In the
      hippocampus, the TRPV1 channel is a novel mediator of long-term depression (LTD)
      at excitatory synapses on interneurons. Here we tested the role of other TRPV
      channels in hippocampal synaptic plasticity, using hippocampal slices from Trpv1,
      Trpv3 and Trpv4 knockout (KO) mice. LTD at excitatory synapses on s. radiatum
      hippocampal interneurons was attenuated in slices from Trpv3 KO mice (as well as
      in Trpv1 KO mice as previously reported), but not in slices from Trpv4 KO mice. A
      previous study found that in hippocampal area CA1, slices from Trpv1 KO mice have
      reduced tetanus-induced long-term potentiation (LTP) following high-frequency
      stimulation; here we confirmed this and found a similar reduction in Trpv3 KO
      mice. We hypothesized that the loss of LTD at the excitatory synapses on local
      inhibitory interneurons caused the attenuated LTP in the mutants. Consistent with
      this idea, blocking GABAergic inhibition rescued LTP in slices from Trpv1 KO and
      Trpv3 KO mice. Our findings suggest a novel role for TRPV3 channels in synaptic
      plasticity and provide a possible mechanism by which TRPV1 and TRPV3 channels
      modulate hippocampal output.

PMID- 23536488
TI  - Caffeine improved paroxysmal dyskinesia caused by the PRRT2 mutation.

PMID- 23536489
TI  - Chromatin remodelling initiation in spermatids: differences among human males.
AB  - During the last phase of spermatogenesis, called spermiogenesis, the nucleosome
      based chromatin structure is replaced by a protamine-based DNA packaging. Not
      much is known about the chromatin remodelling involved in humans and animals.
      Here, we have investigated initiation of chromatin remodelling over seven
      probands of which five were diagnosed with non-obstructive azoospermia (NOA) and
      two with obstructive azoospermia (OA) (failed vaso-vasostomy patients with proven
      fertility prior to vasectomy, Johnsen scores >=9). Chromatin remodelling was
      studied evaluating the presence of nucleosomes, histone H3, pre-protamine 2 and
      protamine 1. This approach was feasible since the local initiation of nucleosome
      eviction in the sub acrosomal domain, which was visible in alkaline nuclear
      spread preparations. The patterns of nucleosome and H3 loss were largely
      congruent. Nucleus wide incorporation of protamine 1 could already be observed at
      the late round spermatid stage. Both for nucleosome loss and for protamine 1
      incorporation, there was distinct variation within and between probands. This did
      not relate to the efficiency of sperm production per meiocyte. Pre-protamine 2
      was always confined to the subacrosomal domain, confirming the role of this area
      in chromatin remodelling.

PMID- 23536491
TI  - Transformation of cavoportal inflow to renoportal inflow to the graft during
      liver transplantation for stage IV portal vein thrombosis.

PMID- 23536490
TI  - A pilot staging system to predict persistent obstructive sleep apnea in children
      following adenotonsillectomy.
AB  - OBJECTIVES/HYPOTHESIS: A recent meta-analysis by Friedman et al. found that 66%
      of children have resolution of obstructive sleep apnea (OSA) after tonsillectomy
      and adenoidectomy (TA). However, accurate predictors of persistent OSA in
      children despite surgery are difficult to identify. We evaluate the utility of
      staging children with OSA using characteristics predictive of adult palatoplasty
      success. STUDY DESIGN: A retrospective analysis of children who underwent sleep
      studies before and after TA in a tertiary care center from 2008 through 2011.
      METHODS: Tonsil size (TS)/modified Mallampati position score (MMP)/body mass
      index (BMI) z Score were used to categorize patients into a three- and four-stage
      tonsillectomy staging system. Stage 1 included patients with low MMP scores/large
      tonsils; stage 2 with low MMP scores/small tonsils or high MMP scores/large
      tonsils. Stage 3 included patients with high MMP scores/small tonsils. For the
      four-stage system, any patient with a BMI z Score >=2.0 was stage 4. RESULTS:
      Thirty-five patients (14 females) were included (mean age, 6.8 years; range, 1.0
      18.6 years). OSA severity ranged from mild (n = 6), moderate (n = 10), to severe
      (n = 19), with a mean respiratory disturbance index (RDI) of 20.9 before surgery
      and 2.4 after. Similar to results seen for adult palatoplasty, staging by
      TS/MMP/BMI corresponded with response to surgery. In stage 1 to 2, 11/17 (64.7%)
      children had RDI <1.5 postoperatively, with decreasing TA success rates in stages
      3 to 4 at 10/18 (55.5%). Although these results were not statistically
      significant (P = .14), the trend was similar to the adult analysis. CONCLUSIONS:
      A trend toward a dose-response relationship was seen between physical exam
      staging and persistent OSA after TA. Further data collection and analysis with a
      larger sample size are warranted.

PMID- 23536492
TI  - New conjugated oligothiophenes containing the unique arrangement of internal
      adjacent [all]-S,S-oxygenated thiophene fragments.
AB  - The quest for obtaining conjugated oligothiophene-containing molecules with
      narrower HOMO-LUMO gaps and higher oxidation and reduction potentials is the
      subject of this study. Molecules containing the bithiophene tetraoxide (2) and
      the terthiophene hexaoxide (3) moieties were prepared and studied. They were
      obtained by transferring oxygen atoms to the corresponding dibromo
      oligothiophenes with the HOF?CH3CN complex and then cross-coupling them with
      either thiophene- or acetylene tin derivatives. The photophysical and
      electrochemical studies of the products revealed that this particular class of
      mixed thiophenes is characterized by significantly smaller frontier orbital gaps
      and higher oxidation and reduction potentials compared with any other arrangement
      of oligothiophenes including various [all]-S,S-oxygenated thiophene derivatives.

PMID- 23536493
TI  - Transient activation of mTOR following forced treadmill exercise in rats.
AB  - The beneficial effect of exercise on hippocampal plasticity is possibly mediated
      by increased angiogenesis and neurogenesis. In angiogenesis, insulin-like growth
      factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and hypoxia
      inducible factor 1, alpha subunit (HIF1alpha) are important factors, while the
      induction of neurogenesis requires signaling through the VEGF receptor, Flk-1
      (VEGFR-2). VEGF expression is believed to be regulated by two distinct mTOR
      (mammalian target of Rapamycin)-containing multiprotein complexes mTORC1 and
      mTORC2, respectively. This study was initiated to investigate the effect of
      exercise on the expression of VEGF, cognate receptors, HIF1alpha, mTORC1, and
      mTORC2 in hippocampus and frontal cortex. To this end, we measured messenger RNA
      (mRNA) levels in rat brain using quantitative real-time polymerase chain reaction
      (real-time qPCR) after forced treadmill exercise for 1 day, 2 weeks, and 8 weeks.
      Rats were euthanized either immediately (0 h) or 24 h after last exercise
      session. Here, we show that exercise affected mRNA levels of VEGF, VEGFR2, and
      the coreceptor neuropilin 2 (NRP2) when the rats were euthanized immediately,
      whereas at 24 h only the expression of mTOR was regulated after a single bout of
      exercise. In conclusion, the effect of treadmill exercise on the VEGF system is
      acute rather than chronic and there is a transient activation of mTOR. More
      studies are needed to understand whether this could be beneficial in the
      treatment of neuropsychiatric disorders.

PMID- 23536494
TI  - Genistein attenuates ischemic oxidative damage and behavioral deficits via
      eNOS/Nrf2/HO-1 signaling.
AB  - Global cerebral ischemia, such as occurs following cardiac arrest, can lead to
      oxidative stress, hippocampal neuronal cell death, and cognitive defects. The
      current study examined the potential beneficial effect and underlying mechanisms
      of post-treatment with the naturally occurring isoflavonic phytoestrogen,
      genistein, which has been implicated to attenuate oxidative stress. Genistein (1
      mg kg(-1)) was administered i.v. 5 min after reperfusion in rats subjected to
      four-vessel global cerebral ischemia (GCI). The results revealed that genistein
      exerted significant neuroprotection of hippocampal CA1 neurons following GCI, as
      evidenced by an increase in NeuN-positive neurons and the decrease in TUNEL
      positive neurons. Furthermore, genistein treatment also resulted in significantly
      improved spatial learning and memory as compared to vehicle control animals. The
      beneficial effects of genistein appear to be mediated by an increase of
      phosphorylation/activation of eNOS, with subsequent activation of the
      antioxidant/detoxification Nrf2/Keap1 transcription system. Along these lines,
      genistein increased keap1 S-nitrosylation, with a corresponding nuclear
      accumulation and enhanced DNA binding activity of Nrf2. Genistein also enhanced
      levels of the Nrf2 downstream antioxidant protein, heme oxygenase (HO)-1, as
      compared to vehicle control groups. In accordance with its induction of Nrf2
      activation, genistein exerted a robust attenuation of oxidative DNA damage and
      lipid peroxidative damage in hippocampal CA1 neurons after GCI, as measured by
      immunofluorescence staining of the oxidative stress markers, 8-hydroxy-2
      deoxyguanosine (8-OHdG) and 4-Hydroxynonenal (4-HNE). Interestingly, the
      aforementioned effects of genistein were abolished by pretreatment with L-NAME,
      an inhibitor of eNOS activation. In conclusion, the results of the study
      demonstrate that low dose genistein can exert significant antioxidant,
      neuroprotective, and cognitive-enhancing effects in the hippocampal CA1 region
      following GCI. Mechanistically, the beneficial effects of genistein appear to be
      mediated by enhanced eNOS phosphorylation/activation and nitric oxide (NO)
      mediated thiol modification of Keap1, with subsequent upregulation of the Nrf2/HO
      1 antioxidative signaling pathway and a resultant attenuation of oxidative
      stress.

PMID- 23536495
TI  - Serum alpha-fetoprotein level independently predicts posttransplant survival in
      patients with hepatocellular carcinoma.
AB  - We aimed to determine whether combining serum alpha-fetoprotein (AFP) level with
      hepatocellular carcinoma (HCC) tumor burden would allow better stratification of
      posttransplant survival for patients with HCC undergoing liver transplantation.
      Adjusting for donor and recipient characteristics, we calculated the risk of
      posttransplant mortality associated with serum AFP level or HCC tumor burden for
      all first-time adult liver transplants performed in the United States between
      2002 and 2011 (n = 45,267). Serum AFP level, rather than tumor burden, was the
      tumor characteristic most strongly associated with posttransplant survival.
      Although recipients with HCC and a serum AFP level <= 15 ng/mL at the time of
      transplantation had no excess posttransplant mortality [adjusted hazard ratio
      (AHR) = 1.02, 95% confidence interval (CI) = 0.93-1.12], patients with a serum
      AFP level of 16 to 65 ng/mL (AHR = 1.38, 95% CI = 1.23-1.54), patients with a
      serum AFP level of 66 to 320 ng/mL (AHR = 1.65, 95% CI = 1.45-1.88), and patients
      with a serum AFP level > 320 ng/mL (AHR = 2.37, 95% CI = 2.06-2.73) had
      progressively worse posttransplant mortality in comparison with recipients
      without HCC. Patients with a tumor burden exceeding the Milan criteria (who are
      usually excluded from transplantation) had excellent posttransplant survival if
      their serum AFP level was 0 to 15 ng/mL (AHR = 0.97, 95% CI = 0.66-1.43). In
      contrast, patients within the Milan criteria (who are routinely considered to be
      transplant candidates) had poor survival if their serum AFP level was
      substantially elevated (for a serum AFP level >= 66 ng/mL, AHR = 1.93, 95% CI =
      1.74-2.15). Changes in serum AFP level while patients were on the waiting list
      corresponded closely to changes in posttransplant mortality. In conclusion, the
      absolute serum AFP level and changes in the serum AFP level strongly predict
      posttransplant survival independently of the tumor burden. We hope that these
      data, in combination with other factors, can be used to inform future studies and
      ongoing discussions aimed at improving the eligibility criteria for liver
      transplantation for patients with HCC.

PMID- 23536496
TI  - Tympanic membrane repair using silk fibroin and acellular collagen scaffolds.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of silk fibroin scaffolds (SFS)
      and acellular collagen scaffolds (ACS) for the repair of tympanic membrane (TM)
      in a guinea pig acute perforation model. STUDY DESIGN: Experimental animal
      research. METHODS: Seventy-two albino guinea pigs underwent perforation of the
      right TM and were divided into four experimental groups (n = 18). The
      perforations were repaired with SFS, ACS, and paper patch using onlay
      myringoplasty, or they were allowed to heal spontaneously (control). An
      additional group of 10 guinea pigs without perforation or scaffold was allocated
      as a normal TM group. Guinea pigs in each experimental group (n = 6) were
      evaluated at 7, 14, and 28 days following surgery. TM structural healing was
      evaluated by otomicroscopy and histology, and functional hearing was analyzed by
      auditory brainstem responses (ABR). Prior to the study, mechanical properties of
      SFS and ACS were investigated. RESULTS: Tensile strength and elasticity of SFS
      and ACS were within the known range for human TM. Based on otologic and
      histologic evaluation, TMs treated with SFS or ACS showed complete closure of the
      perforation at an earlier stage, with a trilaminar structure and more uniform
      thickness compared to paper patch and control treated groups. ABR assessment
      demonstrated that SFS or ACS treatment facilitated a faster restoration of
      hearing function compared to paper patch and control groups. CONCLUSION: The
      results of this study show that SFS and ACS are effective graft materials and may
      be utilized as alternatives to current grafts for TM repair.

PMID- 23536497
TI  - Molecular recognition of rosmarinic acid from Salvia sclareoides extracts by
      acetylcholinesterase: a new binding site detected by NMR spectroscopy.
AB  - Acetylcholinesterase (AChE) inhibition is one of the most currently available
      therapies for the management of Alzheimer's disease (AD) symptoms. In this
      context, NMR spectroscopy binding studies were accomplished to explain the
      inhibition of AChE activity by Salvia sclareoides extracts. HPLC-MS analyses of
      the acetone, butanol and water extracts eluted with methanol and acidified water
      showed that rosmarinic acid is present in all the studied samples and is a major
      constituent of butanol and water extracts. Moreover, luteolin 4'-O-glucoside,
      luteolin 3',7-di-O-glucoside and luteolin 7-O-(6''-O-acetylglucoside) were
      identified by MS(2) and MS(3) data acquired during the LC-MS(n) runs.
      Quantification of rosmarinic acid by HPLC with diode-array detection (DAD) showed
      that the butanol extract is the richest one in this component (134 MUg mg(-1)
      extract). Saturation transfer difference (STD) NMR spectroscopy binding
      experiments of S. sclareoides crude extracts in the presence of AChE in buffer
      solution determined rosmarinic acid as the only explicit binder for AChE.
      Furthermore, the binding epitope and the AChE-bound conformation of rosmarinic
      acid were further elucidated by STD and transferred NOE effect (trNOESY)
      experiments. As a control, NMR spectroscopy binding experiments were also carried
      out with pure rosmarinic acid, thus confirming the specific interaction and
      inhibition of this compound against AChE. The binding site of AChE for rosmarinic
      acid was also investigated by STD-based competition binding experiments using
      Donepezil, a drug currently used to treat AD, as a reference. These competition
      experiments demonstrated that rosmarinic acid does not compete with Donepezil for
      the same binding site. A 3D model of the molecular complex has been proposed.
      Therefore, the combination of the NMR spectroscopy based data with molecular
      modelling has permitted us to detect a new binding site in AChE, which could be
      used for future drug development.

PMID- 23536498
TI  - Sperm DNA fragmentation and morphological degeneration in chilled elephant
      (Elephas maximus and Loxodonta Africana) semen collected by transrectal massage.
AB  - Ejaculates from nine Asian and two African elephants were analysed to gain a
      further understanding of mechanisms underlying variable semen quality after
      transrectal massage. Semen analysis was performed after collection (0 h;
      subjective motility parameters only) and after 24 h of chilled storage at 10 
      degrees C (24 h; all ejaculate and sperm characteristics). Ejaculates with <=50%
      total motility (TM) at 24 h, which represented >90% of collection attempts,
      contained a sperm population with a high degree of DNA damage (64.2 +/- 19.2%
      fragmented DNA) and an elevated incidence of detached heads (43.3 +/- 22.5%). In
      contrast, good quality ejaculates designated as those with >50% TM at 24 h
      displayed higher (p < 0.05) values of sperm kinetic parameters, DNA integrity and
      normal morphology. Fertility potential was high for good quality ejaculates from
      two males (one Asian and one African bull) based on in vitro characteristics
      after chilled storage for up to 48 h post-collection. Urine contamination of
      semen, as assessed quantitatively by creatinine concentration, was confirmed as a
      significant factor in reduced elephant ejaculate quality. However, the
      identification of considerable DNA damage and morphological degeneration in the
      majority of ejaculates after only 24 h of chilled storage indicates that sperm
      ageing could be a primary contributor to inconsistent semen quality in the
      elephant.

PMID- 23536499
TI  - A comparison of two multisegment foot models in high-and low-arched athletes.
AB  - BACKGROUND: Malalignment and dysfunction of the foot have been associated with an
      increased propensity for overuse and traumatic injury in athletes. Several
      multisegment foot models have been developed to investigate motions in the foot.
      However, it remains unknown whether the kinematics measured by different
      multisegment foot models are equivocal. The purpose of the present study is to
      examine the efficacy of two multisegment foot models in tracking aberrant foot
      function. METHODS: Ten high-arched and ten low-arched female athletes walked and
      ran while ground reaction forces and three-dimensional kinematics were tracked
      using the Leardini and Oxford multisegment foot models. Ground reaction forces
      and joint angles were calculated with Visual 3D (C-Motion Inc, Germantown, MD).
      Repeated-measures analyses of variance were used to analyze peak eversion, time
      to peak eversion, and eversion excursions. RESULTS: The Leardini model was more
      sensitive to differences in peak eversion angles than the Oxford model. However,
      the Oxford model detected differences in eversion excursion values that the
      Leardini model did not detect. CONCLUSIONS: Although both models found
      differences in frontal plane motion between high- and low-arched athletes, the
      Leardini multisegment foot model is suggested to be more appropriate as it
      directly tracks frontal plane midfoot motion during dynamic motion.

PMID- 23536500
TI  - Plantar loading asymmetry in American Indians with diabetes and peripheral
      neuropathy, with diabetes only, and without diabetes.
AB  - BACKGROUND: We investigated plantar loading asymmetry during gait in American
      Indians with and without diabetes and with diabetes and peripheral neuropathy.
      METHODS: A convenience sample of 96 American Indians with and without diabetes
      was divided into three groups: 20 with diabetes and peripheral neuropathy, 16
      with diabetes without peripheral neuropathy, and 60 with no history of diabetes
      (control group). Plantar loading was measured during barefoot walking across a
      pressure platform. Five trials were collected per foot during level walking at a
      self-selected speed using the two-step method. Asymmetry in peak pressure-time
      integral and peak plantar pressure were calculated from ten plantar regions and
      compared among groups. RESULTS: Significant pressure-time integral asymmetry
      occurred across the forefoot regions in American Indians with diabetes and
      peripheral neuropathy compared with the other two groups. Significant peak
      plantar pressure asymmetry occurred in the third metatarsal region in both groups
      with diabetes (with and without peripheral neuropathy) compared with the control
      group. CONCLUSIONS: Overall, American Indians with diabetes seemed to show
      greater asymmetry in plantar loading variables across the forefoot region
      compared with those in the control group. Specifically, individuals with diabetes
      and peripheral neuropathy had the greatest amount of forefoot pressure-time
      integral asymmetry. Significant peak plantar pressure asymmetry occurred in the
      third metatarsal region of the forefoot in those with diabetes with and without
      peripheral neuropathy. Loading asymmetry may play a role in the development of
      foot ulcers in the forefoot region of American Indians with peripheral neuropathy
      and diabetes.

PMID- 23536501
TI  - Foot overuse diseases in rock climbing: an epidemiologic study.
AB  - BACKGROUND: Literature examining the incidence of foot diseases in rock climbing
      is limited to traumatic injuries. We examined a large sample of climbers,
      assessed the chronic diseases of the foot, and correlated them with foot
      morphology, shoe type, and type of climbing practiced. METHODS: Between May 1 and
      September 30, 2009, 144 climbers (mean age, 31.7 years) were examined to analyze
      the effect of rock climbing on the various foot diseases found at the time of the
      evaluation. RESULTS: Eighty-six percent of the climbers were affected by a
      pathologic condition. Nail disease was found in 65.3% of patients, followed by
      recurrent ankle sprains (27.8%), retrocalcaneal bursitis (19.4%), Achilles
      tendinitis (12.5%), metatarsalgia (12.5%), and plantar fasciitis (5.6%). Male
      sex, the use of high-type shoes, the high degree of climbing difficulty, and the
      competitive level were often related to the onset of foot diseases. Climbing
      shoes are usually smaller than common footwear. This "shoe-size reduction"
      averaged 2.3 sizes, forcing the foot into a supinated and cavus posture that
      favors lateral instability. The posterior edge of the shoe aperture produces
      increased pressure on the heel, with retrocalcaneal bursitis. CONCLUSIONS:
      Overuse foot diseases related to rock climbing are particularly frequent and
      debilitating. Detailed knowledge of these diseases and their predisposing factors
      may help us implement effective preventive or therapeutic measures, including
      changes in the type of climbing, correction of body weight, degree of difficulty,
      footwear, orthoses, and measures that maximize the support of the foot to the
      ground.

PMID- 23536502
TI  - The effect of moderate running on foot posture index and plantar pressure
      distribution in male recreational runners.
AB  - BACKGROUND: Fatigue due to running has been shown to contribute to changes in
      plantar pressure distribution. However, little is known about changes in foot
      posture after running. We sought to compare the foot posture index before and
      after moderate exercise and to relate any changes to plantar pressure patterns.
      METHODS: A baropodometric evaluation was made, using the FootScan platform
      (RSscan International, Olen, Belgium), of 30 men who were regular runners and
      their foot posture was examined using the Foot Posture Index before and after a
      60-min continuous run at a moderate pace (3.3 m/sec). RESULTS: Foot posture
      showed a tendency toward pronation after the 60-min run, gaining 2 points in the
      foot posture index. The total support and medial heel contact areas increased, as
      did pressures under the second metatarsal head and medial heel. CONCLUSIONS:
      Continuous running at a moderate speed (3.3 m/sec) induced changes in heel strike
      related to enhanced pronation posture, indicative of greater stress on that zone
      after physical activity. This observation may help us understand the functioning
      of the foot, prevent injuries, and design effective plantar orthoses in sport.

PMID- 23536503
TI  - The stationary configuration of the knee.
AB  - BACKGROUND: Ligaments and cartilage contact contribute to the mechanical
      constraints in the knee joints. However, the precise influence of these
      structural components on joint movement, especially when the joint constraints
      are computed using inverse dynamics solutions, is not clear. METHODS: We present
      a mechanical characterization of the connections between the infinitesimal twist
      of the tibia and the femur due to restraining forces in the specific tissue
      components that are engaged and responsible for such motion. These components
      include the anterior cruciate, posterior cruciate, medial collateral, and lateral
      collateral ligaments and cartilage contact surfaces in the medial and lateral
      compartments. Their influence on the bony rotation about the instantaneous screw
      axis is governed by restraining forces along the constraints explored using the
      principle of reciprocity. RESULTS: Published kinetic and kinematic joint data
      (American Society of Mechanical Engineers Grand Challenge Competition to Predict
      In Vivo Knee Loads) are applied to define knee joint function for verification
      using an available instrumented knee data set. We found that the line of the
      ground reaction force (GRF) vector is very close to the axis of the knee joint.
      It aligns the knee joint with the GRF such that the reaction torques are
      eliminated. The reaction to the GRF will then be carried by the structural
      components of the knee instead. CONCLUSIONS: The use of this reciprocal system
      introduces a new dimension of foot loading to the knee axis alignment. This
      insight shows that locating knee functional axes is equivalent to the static
      alignment measurement. This method can be used for the optimal design of braces
      and orthoses for conservative treatment of knee osteoarthritis.

PMID- 23536504
TI  - Diagnosis of hyperostosis of the medial calcaneal tubercle similar to a heel
      spur.
AB  - Calcaneal osteochondromas are rare conditions. To our knowledge, we present the
      first report of a calcaneal osteochondroma in an adolescent patient that was
      surprisingly similar to a heel spur, and, in addition, symptoms due to
      compression of the medial plantar nerve were present.

PMID- 23536505
TI  - Another cystic lesion in the calcaneus: benign fibrous histiocytoma of bone.
AB  - Benign fibrous histiocytoma is a rare benign primary skeletal tumor that occurs
      frequently in the long bones and the pelvis. The calcaneus is an unusual location
      for benign fibrous histiocytoma. We did not identify any case of benign fibrous
      histiocytoma involving the calcaneus in the relevant literature. We describe a 22
      year-old male patient with benign fibrous histiocytoma involving the calcaneus
      treated with curettage and bone grafting. At the final follow-up visit, 1 year
      after surgery, the patient was free of pain and walking unaided. We discuss the
      differential diagnosis of cystic lesions of the calcaneus.

PMID- 23536506
TI  - Deep venous thrombosis and pulmonary embolism as rare complications after hallux
      valgus surgery: case report and literature review.
AB  - The incidence and life-threatening complications of thromboembolic disease after
      major orthopedic surgical procedures have been extensively defined in the medical
      literature. However, there are few studies concerning the incidence of
      thromboembolic disease after foot and ankle surgery. We describe a 57-year-old
      female patient who underwent surgery for bilateral hallux valgus deformities and
      was diagnosed as having deep venous thrombosis and pulmonary embolism after the
      surgery despite early mobilization and mechanical prohylaxis. Her preoperative
      physical examination revealed varicose veins in both cruris. She was treated for
      pulmonary embolism with low-molecular-weight heparin and an oral anticoagulant in
      the postoperative period. Although venous thromboembolism is more commonly
      described after proximal lower-extremity procedures, it can occur after foot and
      ankle surgery, particularly if the patient has certain risk factors. Therefore,
      in addition to mechanical prophylaxis, pharmacologic prophylaxis should be kept
      in mind in such patients.

PMID- 23536507
TI  - Primary squamous cell carcinoma of the distal hallux.
AB  - Squamous cell carcinoma is a common disease of cutaneous tissue with a great
      ability to form metastases. Squamous cell carcinoma is found most commonly on sun
      damaged skin and has a rare occurrence on the toes and feet. The patient was a 68
      year-old woman who was seen at a podiatric specialty office with a complaint of
      pain in her left great toe and toenail. Radiographs displayed erosion of the
      distal hallux, and magnetic resonance imaging revealed no further spread of
      disease in the proximal phalanx. An amputation was performed of the hallux
      interphalangeal joint, and pathology confirmed squamous cell carcinoma of the
      verrucous type.

PMID- 23536508
TI  - Cerebrotendinous xanthomatosis presenting with bilateral achilles tendon
      xanthomata: a case report.
AB  - Xanthomas are described as deposits in the skin and subcutaneous tissues. Mostly
      known as pseudotumors, xanthomas consist of connective tissue containing mainly
      cholesterol, triglycerides, and numerous foamy macrophages. Bilateral Achilles
      tendon xanthomata is pathognomonic for cerebrotendinous xanthomatosis in the case
      of normal cholesterol levels but increased cholestanol levels in serum. In this
      article, we present findings regarding bilateral xanthomas of Achilles tendons in
      a patient with cerebrotendinous xanthomatosis.

PMID- 23536509
TI  - The professor position and the single-stance flexion test may clarify the effect
      of lumbar spinal stenosis or pseudostenosis on lower-extremity symptoms.
AB  - The effect of lumbar spinal stenosis on lower-extremity symptoms is often hard to
      ascertain in patients with multiple possible causes of symptoms. A positive
      response to two described maneuvers performed by patients in the office involving
      flexion of the spine can strongly corroborate the contribution of lumbar spinal
      stenosis to lower-extremity symptoms, although a negative response does not
      negate it. The professor position involves the patient standing and leaning in a
      gentle flexion position, with hands held secure behind the lower back. The single
      stance flexion test has the patient gently leaning on support, with only a single
      symptomatic extremity supporting his or her body weight. Reduction or elimination
      of lower-extremity symptoms otherwise experienced in an erect position suggests
      that spine position contributes significantly to the overall lower-extremity
      symptoms, in addition to or instead of weightbearing or dependent positioning.
      These maneuvers may be effective in either lumbar spinal stenosis or
      pseudostenosis, a condition in which lower-extremity mechanical dysfunction
      induces spinal dysfunction mimicking or exacerbating symptoms of lumbar spinal
      stenosis. Success with either maneuver can suggest to both physician and patient
      the potential value of positional testing with a rolling walker as a therapeutic
      intervention. Further research is necessary. Clinical use may be indicated.

PMID- 23536510
TI  - Toward a change in syntax in diabetic foot care: prevention equals remission.
AB  - Because neuroischemic complications are associated with a high rate of
      recurrence, we propose a slight shift in the mechanism by which we counsel and
      communicate risk daily with our patients. If the epidemiology of this problem is
      comparable with that of cancer, and recurrences are common, then perhaps language
      commensurate with such risks should follow. After initial healing of an index
      wound, our unit now refers to patients not as being cured but rather as being "in
      remission." This concept is easy for the patient and the rest of the team to
      understand. We believe that it powerfully connotes the necessity for frequent
      follow-up and rapid intervention for inevitable minor and sometimes major
      complications.

PMID- 23536511
TI  - Time-dependent degradation pattern of cardiac troponin T following myocardial
      infarction.
AB  - BACKGROUND: Cardiac troponin T (cTnT) is widely used for the diagnosis of acute
      myocardial infarction (AMI). However, it is still unclear whether degraded cTnT
      forms circulate in the patient's blood. We therefore aimed to elucidate which
      cTnT forms are detected by the clinical assay. METHODS: Separation of cTnT forms
      by gel filtration chromatography (GFC) was performed in sera from 13 AMI patients
      to examine cTnT degradation. The GFC eluates were subjected to Western blot
      analysis with the original antibodies from the Roche immunoassay used to mimic
      the clinical cTnT assay. To investigate the degradation pattern with time,
      standardized serum samples of 18 AMI patients collected 0-72 h after admission
      were analyzed by Western blot analysis. RESULTS: GFC analysis of AMI patients'
      sera revealed 2 cTnT peaks with retention volumes of 5 and 21 mL. Western blot
      analysis identified these peaks as cTnT fragments of 29 and 14-18 kDa,
      respectively. Furthermore, the performance of direct Western blots on
      standardized serum samples demonstrated a time-dependent degradation pattern of
      cTnT, with fragments ranging between 14 and 40 kDa. Intact cTnT (40 kDa) was
      present in only 3 patients within the first 8 h after hospital admission.
      CONCLUSIONS: These results demonstrate that the Roche cTnT immunoassay detects
      intact as well as degraded cTnT forms in AMI patients' sera during the period of
      diagnostic testing. Moreover, following AMI, cTnT is degraded in a time-dependent
      pattern.

PMID- 23536512
TI  - FDA oversight of laboratory-developed tests: is it necessary, and how would it
      impact clinical laboratories?

PMID- 23536513
TI  - Gestational diabetes mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus, defined as diabetes diagnosed during
      pregnancy that is not clearly overt diabetes, is becoming more common as the
      epidemic of obesity and type 2 diabetes continues. Newly proposed diagnostic
      criteria will, if adopted universally, further increase the prevalence of this
      condition. Much controversy surrounds the diagnosis and management of gestational
      diabetes. CONTENT: This review provides information regarding various approaches
      to the diagnosis of gestational diabetes and the recommendations of a number of
      professional organizations. The implications of gestational diabetes for both the
      mother and the offspring are described. Approaches to self-monitoring of blood
      glucose concentrations and treatment with diet, oral medications, and insulin
      injections are covered. Management of glucose metabolism during labor and the
      postpartum period are discussed, and an approach to determining the timing of
      delivery and the mode of delivery is outlined. SUMMARY: This review provides an
      overview of current controversies as well as current recommendations for
      gestational diabetes care.

PMID- 23536514
TI  - Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene
      expression in the lipid droplet synthesis pathways.
AB  - It is clear that particulate air pollution poses a serious risk to human health;
      however, the underlying mechanisms are not completely understood. We investigated
      pulmonary transcriptional responses in mice following in-situ exposure to ambient
      air in a heavily industrialized urban environment. Mature C57BL/CBA male mice
      were caged in sheds near two working steel mills and a major highway in Hamilton,
      Ontario, Canada in the spring/summer of 2004. Control mice were housed in the
      same environment, but received only high-efficiency particle filtered air (HEPA).
      Whole lung tissues were collected from mice exposed for 3, 10, or for 10 weeks
      followed by 6 weeks recovery in the laboratory (16 weeks). DNA microarrays were
      used to profile changes in pulmonary gene expression. Transcriptional profiling
      revealed changes in the expression of genes implicated in the lipid droplet
      synthesis (Plin I, Dgat2, Lpl, S3-12, and Agpat2), and antioxidant defense (Ucp1)
      pathways in mice breathing unfiltered air. We postulate that exposure to urban
      air, containing an abundance of particulate matter adsorbed with polycyclic
      aromatic hydrocarbons, triggers lipid droplet (holding depots for lipids and
      malformed/excess proteins tagged for degradation) synthesis in the lungs, which
      may act to sequester particulates. Increased lipid droplet synthesis could lead
      to endogenous/stressor-induced production of reactive oxygen species and
      activation of antioxidant mechanisms. Further investigation into the stimulation
      of lipid droplet synthesis in the lung in response to air pollution and the
      resulting health implications is warranted.

PMID- 23536515
TI  - Electrospun nanofibers as a bioadhesive platform for capturing adherent leukemia
      cells.
AB  - This study investigated the adhesive behaviors of normal and abnormal
      hematopoietic cells on nanotopographical materials. Previously, electrospun
      nanofiber scaffolds (NFSs) were used to capture and expand hematopoietic stem
      cells in vitro; here, we demonstrate that NFS could also serve as a useful
      bioadhesive platform for capturing functionally adherent leukemia cells. Collagen
      blended poly(d,l-lactide-co-glycolide) NFS enabled more rapid and efficient
      capture of K562 leukemia cells than tissue culture polystyrene surfaces with up
      to 70% improved adhesion and shorter time. Cellular extensions, stronger
      adhesion, and enhanced cell-cell interactions were observed in K562 cells
      captured on NFS. While NFS promoted hematopoietic progenitor cell proliferation,
      it inhibited leukemia cell proliferation and affected cell cycle status by
      shifting more cells toward the G0/G1 phase. The expression of alpha-integrins was
      equally high in both captured and uncaptured leukemia cell populations
      demonstrating no relation to its adhesive nature. Hematopoietic morphological
      signatures of NFS captured cells presented no impact on cell differentiation. We
      conclude that electrospun NFS serves as an excellent platform not only for
      capturing functionally adherent leukemia cells but also for studying the impact
      of niche-like structure in the nanoscale.

PMID- 23536516
TI  - Perillyl alcohol as a protective modulator against rat hepatocarcinogenesis via
      amelioration of oxidative damage and cell proliferation.
AB  - In the present study, we have evaluated the chemopreventive effects of perillyl
      alcohol (POH) against diethylnitrosamine-initiated and 2-AAF (2
      acetylaminofluorine)-promoted hepatocarcinogenesis in Wistar rats. Efficacy of
      POH against 2-AAF-induced hepatotoxicity was evaluated in terms of biochemical
      estimation of antioxidant enzyme activities, histopathological changes and
      expression levels of proliferative markers. 2-AAF is a potent hepatotoxicant and
      a hepatic carcinogen that induces its effect by causing oxidative stress. Pre
      treatment of POH prevented oxidative stress and tumour incidences. POH suppressed
      2-AAF-induced early tumour markers, namely ornithine decarboxylase activity,
      thymidine phosphorylase and proliferating cell nuclear antigen (PCNA) protein and
      also suppressed the expression of pro-apoptotic protein P53. Histopathological
      findings revealed that POH-pretreated groups showed marked recovery. From our
      results, it could be concluded that POH markedly protects against chemically
      induced liver cancer and acts possibly by virtue of its antioxidant and
      antiproliferative activities. 

PMID- 23536517
TI  - The protective effects of taurine on experimental acute pancreatitis in a rat
      model.
AB  - The aim of this study was to investigate the protective effects of taurine (Tau)
      on experimental acute pancreatitis (AP) in a rat model by measuring cytokines and
      oxidant stress markers. Forty rats were randomly divided into four groups: sham,
      AP, Tau and AP + Tau. AP was induced with sodium taurocholate. No treatment was
      given to the AP. All rats were killed 5 days later. Pancreatic tissues of rats
      and blood samples were obtained. Tau treatment significantly decreased serum
      amylase activity (p < 0.001), total injury score (p < 0.001), malondialdehyde
      levels (p < 0.001) and myeloperoxidase (MPO) activity (p < 0.001). There was no
      significant difference between the Tau and AP + Tau groups in serum and
      pancreatic tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 levels (p
      = 1.000). Histopathologic scores in the AP + Tau and Tau groups were
      significantly lower compared with the AP group (both p < 0.001). These results
      showed that Tau reduces lipid peroxidation, amylase and MPO activities and the
      concentrations of proinflammatory cytokines secondary to AP and also increases
      superoxide dismutase and glutathione peroxidase activities in rats with sodium
      taurocholate-induced AP. It also has a marked ameliorative effect at
      histopathologic lesions. With these effects, Tau protects the cells from
      oxidative damage, reduces inflammation and promotes regression of pancreatic
      damage.

PMID- 23536518
TI  - Influence of oily vehicles on fetal testis and lipid profile of rats exposed to
      di-butyl phthalate.
AB  - It has been hypothesized that oils containing high levels of omega-3
      polyunsaturated fatty acids, such as canola and fish oil, could counteract some
      of the adverse effects induced by phthalates. In the present study, the influence
      of different oily vehicles on di-butyl phthalate (DBP)-induced testicular
      toxicity and lipid profile was investigated. Pregnant Wistar rats were treated by
      oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in
      three different vehicles: corn, canola or fish oil. Male fetuses were analyzed on
      gestation day 20. DBP exposure lowered intratesticular testosterone levels and
      anogenital distance, regardless of the vehicle used. The percentage of
      seminiferous cords containing multinucleated gonocytes and cord diameter was
      increased in DBP-exposed groups, compared with vehicle controls, with no
      difference between the three DBP-exposed groups. Clustering of Leydig cells was
      seen in all DBP groups. Lipid profile indicated that administration of canola and
      fish oil can increase the content of omega-3 fatty acids in rat testis. However,
      content of omega-3 was diminished in DBP-treated groups. Overall, our results
      indicate that different oily vehicles did not alter fetal rat testicular toxicity
      induced by a high DBP dose.

PMID- 23536519
TI  - Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon
      cancer cells: calorie restriction is the force to the cytotoxicity.
AB  - The aim of this study was to examine the antitumour activity of resveratrol in
      human colorectal cancer cell lines (HCT116 and Caco2) and to explore its
      mechanism of action assuming that it is by calorie-restriction effect.
      Resveratrol inhibited the proliferation of colon cancer cells with half maximal
      inhibitory concentration (IC(50)) equal to 50 and 130 MUM for HCT116 and Caco2,
      respectively. Caco2 cells appeared with significant time-dependent increase in
      the glycolytic pathway, a behaviour that was absent in HCT116 cells. Resveratrol
      (100 MUM) significantly decreased the glycolytic enzymes (pyruvate kinase and
      lactate dehydrogenase) in Caco2 cells, while an increase in citrate synthase
      activity and a decrease in glucose consumption were observed in both cell lines.
      Moreover, resveratrol downregulated the expressions of leptin and c-Myc, and
      decreased the content of vascular endothelial growth factor. The apoptotic
      markers, caspases 3 and 8, were activated and the Bax/BCl2 ratio was increased.
      The study suggested a promising anticancer activity of resveratrol, calorie
      restriction pathway may be one of the driving forces for this activity.

PMID- 23536520
TI  - A new antiallergic agent that binds to dimerized translationally controlled tumor
      protein and inhibits allergic symptoms is nontoxic.
AB  - Dimerized translationally controlled tumor protein (dTCTP) plays a role in
      allergic diseases. A 7-mer peptide, dimerized translationally binding protein 2
      (dTBP2), binds to dTCTP and inhibits dTCTP, suggesting that the 7-mer peptide may
      have therapeutic potential. We assessed the safety of dTBP2 by examining its
      cytotoxicity to both human bronchial epithelial cells and mice. dTBP2 did not
      cause cytotoxicity to the epithelial cells in concentrations up to 100 MUg/ml.
      Also, dTBP2 caused no adverse effects upon repeated administration of 50 mg/kg
      over 24 h to mice. Hence, we conclude that dTBP2 is a safe candidate drug for use
      in the therapy of allergic diseases. 

PMID- 23536522
TI  - The effects of gender difference on monocrotaline-induced pulmonary hypertension
      in rats.
AB  - The present study aimed to compare the effect of gender difference on hemodynamic
      consequences in the development of monocrotaline (MCT)-induced pulmonary
      hypertension in rat. The effect of antioxidant enzyme systems on the development
      of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender
      on these antioxidant systems were also investigated. For this purpose, the right
      ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were
      compared between groups and the glutathione (GSH) level and superoxide dismutase
      (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were
      determined in lung and liver tissue samples of rats. RVP and right ventricular/HW
      ratios significantly increased in the MCT group compared to the control group. In
      the MCT group, RVP was significantly higher in males than females. MCT-induced
      pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD
      activities and increased CAT activity in lung and liver tissues of both male and
      female rats. In addition, the lung and liver GSH level and GST and SOD levels
      were higher in female control rats compared to male control rats. The results of
      the present study, that antioxidant enzyme activities were different between the
      groups, highlight the possible role of oxidative stress in the pathogenesis of
      MCT-induced pulmonary hypertension in rats. Moreover, the lower antioxidant
      defense capacity of male rats than female rats may be considered as a cause of
      more aggressive course of MCT-induced pulmonary hypertension in males compared to
      females.

PMID- 23536521
TI  - Differential effects of organic and inorganic selenium compounds on adenosine
      deaminase activity and scavenger capacity in cerebral cortex slices of young
      rats.
AB  - Selenium (Se) has anti-inflammatory and antioxidant properties and is necessary
      for the development and normal function of the central nervous system. This study
      was aimed to compare the in vitro effects of 3-methyl-1-phenyl-2
      (phenylseleno)oct-2-en-1-one (C21H2HOSe; organoselenium) and sodium selenate
      (inorganic Se) on adenosine deaminase (ADA) activity, cell viability, lipid
      peroxidation, scavenger of nitric oxide (NO) and nonprotein thiols (NP-SH)
      content in the cerebral cortex slices of the young rats. A decrease in ADA
      activity was observed when the slices were exposed to organoselenium at the
      concentrations of 1, 10 and 30 uM. The same compound showed higher scavenger
      capacity of NO than the inorganic compound. Inorganic Se was able to protect
      against sodium nitroprusside-induced oxidative damage and increased the NP-SH
      content. Both the compounds displayed distinctive antioxidant capacities and were
      not cytotoxic for the cerebral cortex slices in the conditions tested. These
      findings are likely to be related to immunomodulatory and antioxidant properties
      of this compound.

PMID- 23536523
TI  - Mechanistic aspects of gas-phase hydrogen-atom transfer from methane to [CO](.+)
      and [SiO](.+) : why do they differ?
AB  - The reactivity of the two diatomic congeneric systems [CO](.+) and [SiO](.+)
      towards methane has been investigated by means of mass spectrometry and quantum
      chemical calculations. While [CO](.+) gives rise to three different reaction
      channels, [SiO](.+) reacts only by hydrogen-atom transfer (HAT) from methane
      under thermal conditions. A theoretical analysis of the respective HAT processes
      reveals two distinctly different mechanistic pathways for [CO](.+) and [SiO](.+),
      and a comparison to the higher metal oxides of Group 14 emphasizes the particular
      role of carbon as a second-row p element.

PMID- 23536524
TI  - Outcome of endoscopic resection tracheoplasty for treating lambdoid tracheal
      stomal stenosis.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of endoscopic resection
      tracheoplasty (ERT) for treating post-tracheotomy stomal stenosis caused by
      inward collapse of tracheal ring remnants. STUDY DESIGN: Prospective
      observational study. METHODS: Between 2007 and 2012, we treated 40 patients with
      "lambdoid" tracheal deformity with a two-staged minimally invasive procedure
      undertaken using suspension microtracheoscopy and high-frequency jet ventilation.
      The first procedure entailed CO2 laser photoablation of collapsed tracheal rings
      and dilatation. The second procedure, performed 6 to 8 weeks later, involved
      ablation of residual structural obstruction, removal of granulation tissue, and
      intralesional corticosteroid injection. Perioperative patient and lesion
      characteristics and results of treatment were assessed. RESULTS: There were 22
      males and 18 females, and mean age at first treatment was 59 years. There were 17
      cases of scarring at the postero-lateral tracheal groove (trachealis blunting),
      and 22 patients had age-adjusted Charlson comorbidity scores greater than 4. All
      patients without trachealis blunting were successfully managed endoscopically,
      with only one patient requiring one additional endoscopic treatment. Seven
      patients with trachealis blunting needed additional treatment, and four patients
      had tracheal resection (P = 0.013). All patients were decannulated, and 75% of
      patients achieved good dyspnea outcomes. Patients with low morbidities were
      significantly more likely to achieve good dyspnea outcomes (P < 0.027). There
      were no treatment-related worsenings of voice or swallowing. CONCLUSIONS: ERT is
      an effective minimally invasive treatment for intubation-related lambdoid
      tracheal stenosis. It achieves a successful outcome while avoiding the risks
      associated with open surgery. We recommend its more widespread use for treating
      patients with this condition.

PMID- 23536525
TI  - Distinct set of kinases induced after retrieval of spatial memory discriminate
      memory modulation processes in the mouse hippocampus.
AB  - Protein phosphorylation and dephosphorylation events play a key role in memory
      formation and various protein kinases and phosphatases have been firmly
      associated with memory performance. Here, we determined expression changes of
      protein kinases and phosphatases following retrieval of spatial memory in CD1
      mice in a Morris Water Maze task, using antibody microarrays and confirmatory
      Western blot. Comparing changes following single and consecutive retrieval, we
      identified stably and differentially expressed kinases, some of which have never
      been implicated before in memory functions. On the basis of these findings we
      define a small signaling network associated with spatial memory retrieval.
      Moreover, we describe differential regulation and correlation of expression
      levels with behavioral performance of polo-like kinase 1. Together with its
      recently observed genetic association to autism-spectrum disorders our data
      suggest a role of this kinase in balancing preservation and flexibility of
      learned behavior.

PMID- 23536526
TI  - Association and cumulative effects of GWAS-identified genetic variants for
      nonsyndromic orofacial clefts in a Chinese population.
AB  - A recent genome-wide meta-analysis identified six new susceptible genetic
      variants for nonsyndromic orofacial clefts (NSOC), but it was still unknown
      whether these newly identified variants were associated with NSOC susceptibility
      in Chinese populations. In this study, we genotyped these variants in a case
      control study of 602 NSOC cases and 605 controls and found that four of these
      variants (rs7590268, rs7632427, rs12543318, and rs1873147) were associated with
      susceptibility to NSOC. We further investigated the cumulative effects of these
      four variants and found a dose-dependent increase in risk with the number of
      variant alleles. Furthermore, an association was observed between rs7590268 and a
      family history of NSOC. Our results provide confirmative evidence that these risk
      loci contribute to NSOC susceptibility in Chinese populations.

PMID- 23536527
TI  - Panel 1: Epidemiology, natural history, and risk factors.
AB  - BACKGROUND: The First International Symposium on Recent Advances in Otitis Media
      (OM) with Effusion was held in Columbus, Ohio, in 1975. The symposium has been
      organized in the United States every 4 years since, followed by a research
      conference to (a) assess major research accomplishments, (b) identify important
      research questions and opportunities, (c) develop consensus on definitions and
      terminology, and (d) establish priorities with short- and long-term research
      goals. One of the principal areas reviewed quadrennially is Epidemiology, Natural
      History, and Risk Factors. OBJECTIVE: To provide a review of recent literature on
      the epidemiology, natural history, and risk factors for OM. DATA SOURCES AND
      REVIEW METHODS: A search of OM articles in English published July 2007 to June
      2011 was conducted using PubMed and related databases. Those with findings judged
      of importance for epidemiology, public health, and/or statistical methods were
      reviewed. RESULTS: The literature has continued to expand, increasing
      understanding of the worldwide burden of OM in childhood, complications from
      treatment failures, and comorbidities. Novel risk factors, including genetic
      factors, have been examined for OM susceptibility. Population-based studies in
      Canada, the United States, and other countries confirmed reductions in OM
      prevalence. Although most studies concentrated on acute OM (AOM) or OM with
      effusion (OME), a few examined severe chronic suppurative OM (CSOM), a major
      public health problem in developing countries and for certain indigenous
      populations around the world. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Recent
      publications have reinforced earlier epidemiological findings, while extending
      our knowledge in human population groups with high burden of OM.

PMID- 23536528
TI  - Panel 7: Treatment and comparative effectiveness research.
AB  - BACKGROUND AND OBJECTIVES: Otitis media (OM) is one of the most common reasons
      for antibiotic treatment in children. Controversies regarding antibiotic
      treatment for OM have accumulated in the past decade, and there seem to be more
      dilemmas than certainties. The objectives of this article are to provide the
      state-of-the art review on achievements in treatment of all different stages of
      OM, including acute otitis media (AOM), otitis media with effusion (OME), and
      chronic suppurative otitis media, and to outline the future research areas. DATA
      SOURCES: PubMed, Ovid Medline, the Cochrane Database, and Clinical Evidence (BMJ
      Publishing). REVIEW METHODS: All types of articles related to OM treatment
      published in English between January 2007 and June 2011 were identified. A total
      of 286 articles related to OM treatment were reviewed by the panel members; 114
      relevant quality articles were identified and summarized. RESULTS: New evidence
      emerged on beneficial results of antibiotic treatment, compared with observation
      of AOM in young children who were diagnosed based on stringent criteria. In OME,
      the main results were related to a nonsignificant benefit of adenoidectomy versus
      tympanostomy tube placement alone in the treatment of chronic OME in younger
      children. Other modalities of OM treatment were studied and described herein.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Significant progress has been made in
      advancing the knowledge on the treatment of OM. Areas of potential future
      research have been identified and outlined.

PMID- 23536529
TI  - Panel 8: Complications and sequelae.
AB  - BACKGROUND AND OBJECTIVES: Although serious complications of otitis media (OM)
      such as brain abscess are rare, sequelae of OM such as tympanic membrane
      perforation and atelectatic tympanic membrane are quite common. Inner ear
      sequelae can cause hearing loss and speech and language problems. The objectives
      of this article are to provide a state-of-the-art review on recent articles on
      complications and sequelae of OM in different anatomic locations, from the
      tympanic membrane to intracranial sites, as well as hearing loss and speech and
      language development. DATA SOURCES: Primarily PubMed supplemented by Ovid MEDLINE
      and the Cochrane Database. REVIEW METHODS: All types of articles related to OM
      complications and sequelae published in English between January 2007 and June
      2011 were identified. A total of 127 relevant quality articles are summarized and
      included in this report. RESULTS: Key findings are summarized based on the
      following major anatomic locations and categories: tympanic membrane;
      cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech
      and language development; extracranial areas, including mastoiditis and facial
      nerve paralysis; intracranial complications; and future research goals. New
      information and insights were gained to prevent complications and sequelae.
      CONCLUSION AND IMPLICATIONS FOR PRACTICE: Over the past 4 years, progress has
      been made in advancing the knowledge on the complications and sequelae of OM,
      which can be used to prevent and treat them effectively. Areas of potential
      future research have been identified and outlined.

PMID- 23536530
TI  - Panel 2: Eustachian tube, middle ear, and mastoid--anatomy, physiology,
      pathophysiology, and pathogenesis.
AB  - OBJECTIVE: This report reviews the literature to identify the advances in our
      understanding of the middle ear (ME)-Eustachian tube (ET) system during the past
      4 years and, on that basis, to determine whether the short-term goals elaborated
      in the last report were achieved and propose updated goals to guide future otitis
      media (OM) research. DATA SOURCES: Databases searched included PubMed, Web of
      Science (1945-present), Medline (1950 to present), Biosis Previews (1969
      present), and the Zoological Record (1978 to present). The initial literature
      search covered the time interval from January 2007 to June 2011, with a
      supplementary search completed in February 2012. REVIEW METHODS: The panel topic
      was subdivided; each contributor performed a literature search and provided a
      preliminary report. Those reports were consolidated and discussed when the panel
      met on June 9, 2011. At that meeting, the progress was evaluated and new short
      term goals proposed. CONCLUSIONS: Progress was made on 16 of the 19 short-term
      goals proposed in 2007. Significant advances were made in the characterization of
      ME gas exchange pathways, modeling ET function, and preliminary testing of
      treatments for ET dysfunction. IMPLICATIONS FOR PRACTICE: In the future, imaging
      technologies should be developed to noninvasively assess ME/ET structure and
      physiology with respect to their role in OM pathogenesis. The new data derived
      from form/function experiments should be integrated into the finite element
      models and used to develop specific hypotheses concerning OM pathogenesis and
      persistence. Finally, rigorous studies of treatments, medical or surgical, of ET
      dysfunction should be undertaken.

PMID- 23536531
TI  - Panel 3: Recent advances in anatomy, pathology, and cell biology in relation to
      otitis media pathogenesis.
AB  - BACKGROUND AND OBJECTIVES: The pathogenesis of otitis media (OM) involves a
      number of factors related to the anatomy, pathology, and cell biology of the
      middle ear, the mastoid, the Eustachian tube, and the nasopharynx. Although some
      issues of pathogenesis are fairly well established, others are only marginally
      indicated by current knowledge, and yet others remain undisclosed. The objective
      of this article is to provide a state-of-the-art review on recent scientific
      achievements in the pathogenesis of OM, as related to anatomy, pathology, and
      cell biology. DATA SOURCES: PubMed, Ovid Medline, and Cochrane Library. REVIEW
      METHODS: Articles published on the pathogenesis of OM and the anatomy, pathology,
      and cell biology of the middle ear, the mastoid, the Eustachian tube, and the
      nasopharynx between January 2007 and June 2011 were identified. Among almost 1900
      abstracts, the authors selected 130 articles for full article review and
      inclusion in this report. RESULTS: New knowledge on a number of issues emerged,
      including cell-specific expression and function of fluid transportation and
      innate immune system molecules, mucous cell metaplasia, mucin expression,
      bacterial adherence, and epithelial internalization, as well as the occurrence,
      composition, dynamics, and potential role of bacterial biofilm. In addition, the
      potential role of gastroesophageal reflux disease and cigarette smoke exposure
      has been explored further. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Over the
      past 4 years, considerable scientific progress has been made on the pathogenesis
      of OM, as related to issues of anatomy, pathology, and cell biology. Based on
      these new achievements and a sustained lack of essential knowledge, suggestions
      for future research are outlined.

PMID- 23536532
TI  - Panel 4: Recent advances in otitis media in molecular biology, biochemistry,
      genetics, and animal models.
AB  - BACKGROUND: Otitis media (OM) is the most common childhood bacterial infection
      and also the leading cause of conductive hearing loss in children. Currently,
      there is an urgent need for developing novel therapeutic agents for treating OM
      based on full understanding of molecular pathogenesis in the areas of molecular
      biology, biochemistry, genetics, and animal model studies in OM. OBJECTIVE: To
      provide a state-of-the-art review concerning recent advances in OM in the areas
      of molecular biology, biochemistry, genetics, and animal model studies and to
      discuss the future directions of OM studies in these areas. DATA SOURCES AND
      REVIEW METHODS: A structured search of the current literature (since June 2007).
      The authors searched PubMed for published literature in the areas of molecular
      biology, biochemistry, genetics, and animal model studies in OM. RESULTS: Over
      the past 4 years, significant progress has been made in the areas of molecular
      biology, biochemistry, genetics, and animal model studies in OM. These studies
      brought new insights into our understanding of the molecular and biochemical
      mechanisms underlying the molecular pathogenesis of OM and helped identify novel
      therapeutic targets for OM. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our
      understanding of the molecular pathogenesis of OM has been significantly
      advanced, particularly in the areas of inflammation, innate immunity, mucus
      overproduction, mucosal hyperplasia, middle ear and inner ear interaction,
      genetics, genome sequencing, and animal model studies. Although these studies are
      still in their experimental stages, they help identify new potential therapeutic
      targets. Future preclinical and clinical studies will help to translate these
      exciting experimental research findings into clinical applications.

PMID- 23536535
TI  - Maxillary swing approach for extended infratemporal fossa tumors.

PMID- 23536536
TI  - Ultrastructural observations of programmed cell death during metanephric
      development in mouse.
AB  - Previous studies revealed apoptosis as an only programmed cell death (PCD) during
      renal morphogenesis before alternative type of PCD, necroptosis were introduced.
      Evidences of non-apoptotic PCD during renal development were scarce and needed to
      be accumulated. The purpose of this study is to investigate whether non-apoptotic
      PCD is involved in and observe ultrastructural features of apoptotic cells or non
      apoptotic PCD during metanephros development. For this purpose, light and
      transmission electron microscopy were used. The most significant finding to come
      out of this study was that necroptosis was observed during developing metanephros
      by electron microscopy. The results also provided another fact that apoptosis and
      necroptosis constituted the PCD during embryonic development of kidney in mouse.
      Compared to necroptosis, apoptosis was more predominantly evident throughout
      whole development period and in every compartment of metanephros except for
      proximal tubule. However, necroptosis was only exhibited in developing nephrons
      also except for proximal tubule. In addition, outcomes of PCD were related to
      morphogenetic features of metanephric development. Efferocytosis for apoptotic
      cell or bodies took place in each type cell and whole period of developing
      metanephros. Besides efferocytosis blood flow and urine flux were available to
      remove the corpses of PCD, especially PCD from developing nephrons. Our findings
      suggested that both apoptosis and necroptosis play important roles during
      nephrogenesis and observed three ways to clear the PCD cell: efferocytosis, blood
      flow, and urine flux.

PMID- 23536537
TI  - Reactions of iron carbenes with alpha,beta-unsaturated esters by using an
      Umpolung approach: mechanism and applications.
AB  - An Umpolung approach, in which a phosphorus ylide moiety was introduced to
      increase the electron density of the double bond, was developed to activate
      electron-deficient alkenes for reaction with electrophilic iron carbenes. In
      tandem with the Wittig reaction, the reactions of alpha,beta-unsaturated esters
      with in situ generated Fe-carbene complexes delivered formal C-H insertion
      products through cyclopropanation/ring-opening reactions. DFT calculations and
      cross-experiments indicate that, in this process, the ring opening of the
      cyclopropylmethyl ylide intermediate is rapid and reversible and the subsequent
      proton transfer is the rate-determining step. Further studies revealed that,
      based on the choice of the ylide and ester groups, as well as the base, the
      reaction could be steered towards either the ring-opening pathway or to the
      production of vinyl cyclopropanes.

PMID- 23536533
TI  - Panel 5: Microbiology and immunology panel.
AB  - OBJECTIVE: The objective is to perform a comprehensive review of the literature
      from January 2007 through June 2011 on the virology, bacteriology, and immunology
      related to otitis media. DATA SOURCES: PubMed database of the National Library of
      Medicine. REVIEW METHODS: Three subpanels with co-chairs comprising experts in
      the virology, bacteriology, and immunology of otitis media were formed. Each of
      the panels reviewed the literature in their respective fields and wrote draft
      reviews. The reviews were shared with all panel members, and a second draft was
      created. The entire panel met at the 10th International Symposium on Recent
      Advances in Otitis Media in June 2011 and discussed the review and refined the
      content further. A final draft was created, circulated, and approved by the
      panel. CONCLUSION: Excellent progress has been made in the past 4 years in
      advancing an understanding of the microbiology and immunology of otitis media.
      Advances include laboratory-based basic studies, cell-based assays, work in
      animal models, and clinical studies. IMPLICATIONS FOR PRACTICE: The advances of
      the past 4 years formed the basis of a series of short-term and long-term
      research goals in an effort to guide the field. Accomplishing these goals will
      provide opportunities for the development of novel interventions, including new
      ways to better treat and prevent otitis media.

PMID- 23536534
TI  - Panel 6: Vaccines.
AB  - OBJECTIVE: To update progress on the effectiveness of vaccine for prevention of
      acute otitis media (AOM) and identification of promising candidate antigens
      against Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and
      Moraxella catarrhalis. REVIEW METHODS: Literature searches were performed in
      OvidSP and PubMed restricted to articles published between June 2007 and
      September 2011. Search terms included otitis media, vaccines, vaccine antigens,
      and each of the otitis pathogens and candidate antigens identified in the ninth
      conference report. CONCLUSIONS: The current report provides further evidence for
      the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of
      otitis media. Observational studies demonstrate a greater decline in AOM episodes
      than reported in clinical efficacy trials. Unmet challenges include extending
      protection to additional serotypes and additional pathogens, the need to prevent
      early episodes, the development of correlates of protection for protein antigens,
      and the need to define where an otitis media vaccine strategy fits with
      priorities for child health. IMPLICATIONS FOR PRACTICE: Acute otitis media
      continues to be a burden on children and families, especially those who suffer
      from frequent recurrences. The 7-valent PCV (PCV7) has reduced the burden of
      disease as well as shifted the pneumococcal serotypes and the distribution of
      otopathogens currently reported in children with AOM. Antibiotic resistance
      remains an ongoing challenge. Multiple candidate antigens have demonstrated the
      necessary requirements of conservation, surface exposure, immunogenicity, and
      protection in animal models. Further research on the role of each antigen in
      pathogenesis, in the development of correlates of protection in animal models,
      and in new adjuvants to elicit responses in the youngest infants is likely to be
      productive and permit more antigens to move into human clinical trials.

PMID- 23536539
TI  - Fluid mechanical consequences of pendular activity, segmentation and pyloric
      outflow in the proximal duodenum of the rat and the guinea pig.
AB  - We conducted numerical experiments to study the influence of non-propagating
      longitudinal and circular contractions, i.e. pendular activity and segmentation,
      respectively, on flow and mixing in the proximal duodenum. A lattice-Boltzmann
      numerical method was developed to simulate the fluid mechanical consequences for
      each of 22 randomly selected sequences of high-definition video of real
      longitudinal and radial contractile activity in the isolated proximal duodenum of
      the rat and guinea pig. During pendular activity in the rat duodenum, the flow
      was characterized by regions of high shear rate. Mixing was so governed by
      shearing deformation of the fluid that increased the interface between adjacent
      domains and accelerated their inter-diffusion (for diffusion coefficients approx.
      less than 10(-8) m&sup2; s(-1)). When pendular activity was associated with a
      slow gastric outflow characteristic of post-prandial period, the dispersion was
      also improved, especially near the walls. Mixing was not promoted by isolated
      segmentative contractions in the guinea pig duodenum and not notably influenced
      by pylorus outflow. We concluded that pendular activity generates mixing of
      viscous fluids 'in situ' and accelerates the diffusive mass transfer, whereas
      segmentation may be more important in mixing particulate suspensions with high
      solid volume ratios.

PMID- 23536538
TI  - Elastin and collagen fibre microstructure of the human aorta in ageing and
      disease: a review.
AB  - Aortic disease is a significant cause of death in developed countries. The most
      common forms of aortic disease are aneurysm, dissection, atherosclerotic
      occlusion and ageing-induced stiffening. The microstructure of the aortic tissue
      has been studied with great interest, because alteration of the quantity and/or
      architecture of the connective fibres (elastin and collagen) within the aortic
      wall, which directly imparts elasticity and strength, can lead to the mechanical
      and functional changes associated with these conditions. This review article
      summarizes the state of the art with respect to characterization of connective
      fibre microstructure in the wall of the human aorta in ageing and disease, with
      emphasis on the ascending thoracic aorta and abdominal aorta where the most
      common forms of aortic disease tend to occur.

PMID- 23536540
TI  - Fick's second law transformed: one path to cloaking in mass diffusion.
AB  - Here, we adapt the concept of transformational thermodynamics, whereby the flux
      of temperature is controlled via anisotropic heterogeneous diffusivity, for the
      diffusion and transport of mass concentration. The n-dimensional, time-dependent,
      anisotropic heterogeneous Fick's equation is considered, which is a parabolic
      partial differential equation also applicable to heat diffusion, when convection
      occurs, for example, in fluids. This theory is illustrated with finite-element
      computations for a liposome particle surrounded by a cylindrical multi-layered
      cloak in a water-based environment, and for a spherical multi-layered cloak
      consisting of layers of fluid with an isotropic homogeneous diffusivity, deduced
      from an effective medium approach. Initial potential applications could be sought
      in bioengineering.

PMID- 23536541
TI  - Aminosilane functionalizations of mesoporous oxidized silicon for oligonucleotide
      synthesis and detection.
AB  - Direct solid phase synthesis of peptides and oligonucleotides (ONs) requires high
      chemical stability of the support material. In this work, we have investigated
      the passivation ability of porous oxidized silicon multilayered structures by two
      aminosilane compounds, 3-aminopropyltriethoxysilane and 3
      aminopropyldimethylethoxysilane (APDMES), for optical label-free ON biosensor
      fabrication. We have also studied by spectroscopic reflectometry the
      hybridization between a 13 bases ON, directly grown on the aminosilane modified
      porous oxidized silicon by in situ synthesis, and its complementary sequence.
      Even if the results show that both devices are stable to the chemicals
      (carbonate/methanol) used, the porous silica structure passivated by APDMES
      reveals higher functionalization degree due to less steric hindrance of pores.

PMID- 23536543
TI  - Chromosome analysis of nuclear power plant workers using fluorescence in situ
      hybridization and Giemsa assay.
AB  - The aim of this study was to evaluate the genotoxic effects of ionizing radiation
      in vivo in exposed Bulgarian nuclear power plant workers by using classical
      cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes.
      Chromosome analysis using fluorescence in situ hybrydization (FISH) and Giemsa
      techniques was undertaken on 63 workers and 45 administrative staff controls from
      the Bulgarian Nuclear Power Plant. Using the Giemsa method, the frequencies of
      cells studied with chromosome aberrations, dicentrics plus rings and chromosome
      fragments in the radiation workers were significantly higher compared with the
      control group (P = 0.044, P = 0.014, and P = 0.033, respectively). A significant
      association between frequencies of dicentrics plus rings and accumulated doses
      was registered (P < 0.01). In the present study, a FISH cocktail of whole
      chromosome paints for chromosomes 1, 4 and 11 was used. A significant association
      between frequency of translocations and accumulated doses was also observed (P <
      0.001). Within the control group, a correlation was found between age and the
      spontaneous frequency of translocations. No correlation was found between smoking
      status and frequency of translocations. When compared with the control group,
      workers with accumulated doses up to 100 mSv showed no increase in genome
      translocation frequency, whereas workers with accumulated doses from 101 to 200
      mSv showed a statistically significant doubling of genome translocation frequency
      (P = 0.009). Thus, in cases of chronic exposure and for purposes of retrospective
      dosimetry, the genome frequency of translocations is a more useful marker for
      evaluation of genotoxic effects than dicentric frequency. 

PMID- 23536544
TI  - Effect of different treatment plans on irradiated small-bowel volume in
      gynecologic patients undergoing whole-pelvic irradiation.
AB  - To evaluate the effect of different treatment plans for whole-pelvic irradiation
      on small-bowel volumes (SBVs) in patients with gynecologic malignancies, 40
      patients were enrolled in this study. Computed tomography (CT) simulations were
      performed, and the small bowel of each patient was outlined manually. Treatment
      plans with equal-weighted (EW) and non-equal-weighted (NEW) (70% in bilateral
      directions) techniques of four-field and intensity-modulated radiation therapy
      (IMRT) were performed. The V10-V100 represented the volume (cm3) at different
      levels of the prescribed doses (10-100%). The V10-V100 was compared among the
      different treatment planning techniques, and patients who were suitable for IMRT
      or NEW were identified. IMRT and NEW significantly reduced the V50-V100 and V40
      V60 levels compared with EW, respectively. NEW caused a significant reduction in
      the V30-V60 levels in patients with a BMI >=26 kg/m2. Patients with IMRT
      demonstrated lower V70-V100 levels compared with those with NEW. In patients with
      a BMI >=26 kg/m2 or an age >=55 years, lower V20-V50 levels were noted using NEW
      compared with IMRT. Treatment planning with larger weighting in the bilateral
      directions in four-field radiotherapy reduces the low-dose SBV in patients with
      gynecologic malignancies, especially in those with a high BMI or the elderly.
      IMRT effectively reduces high-dose SBV, especially in patients with a low BMI.

PMID- 23536545
TI  - Characteristics of Notch2(+) pancreatic cancer stem-like cells and the
      relationship with centroacinar cells.
AB  - Notch2, a surface marker in cell lines, is used to isolate, identify and localise
      pancreatic cancer stem-like cells and is a target for therapy of these cells.
      Sphere formation was induced in Panc-1 and Bxpc-3 pancreatic cancer cell lines,
      and Notch2(+) cells were separated from Bxpc-3 and Panc-1 cell lines by magnetic
      activated cell sorting (MACS). Expression of stem cell-related markers, OCT4,
      Nanog and PDX1, were measured by immunofluorescent (IF) staining. Expression of
      Notch2 was also determined immunohistochemically in pancreatic tissues. Notch2(+)
      cells were transplanted in subcutaneous of mice. AQP1 and AQP5 were also measured
      by IF in Bxpc-3 cells. The Notch signal pathway inhibitor, Compound E (CE), was
      used to treat Notch2(+) Bxpc-3 cells, and their vitalities were subsequently
      measured by the CCK-8 method. Positive expression of OCT4, Nanog and PDX1 was
      observed in Notch2(+) cells. Notch2(+) cells at centroacinar cell (CAC) and
      terminal ductal locations expressed AQP1 and AQP5. They were strongly
      tumourigenic in mice, and CE inhibited proliferation of Notch2(+) Bxpc-3 cells to
      some degree. OCT4 and Nanog can be used as markers of self-renewal in pancreatic
      cancer stem cells. Notch2(+) cells in human pancreatic cancer Bxpc-3 and Panc-1
      cell lines had the properties of cancer stem cells. The results suggest that
      Notch2(+) pancreatic cancer stem-like cells had a close relationship with CAC. 

PMID- 23536548
TI  - A generic, whole-cell-based screening method for Baeyer-Villiger monooxygenases.
AB  - Baeyer-Villiger monooxygenases (BVMOs) have been receiving increasing attention
      as enzymes useful for biocatalytic applications. Industrial requirements call for
      rapid and extensive redesign of these enzymes. In response to the need for
      screening large libraries of BVMO mutants, we established a generic screening
      method that allows screening of Escherichia coli cells expressing active BVMOs in
      96-well plate format. For this, we first developed an expression system for
      production of phenylacetone monooxygenase (PAMO) in the periplasm of E. coli.
      This allows probing the enzyme for any target substrate while it is also
      compatible with extracellular coenzyme regeneration. For coenzyme regeneration,
      we used phosphite dehydrogenase, which forms phosphate upon NADPH recycling. This
      allowed the use of a chromogenic molybdate-based phosphate determination assay.
      The screening procedure was supplemented with a detection method for
      identification of mutant enzymes that act as NADPH oxidases, thereby excluding
      false-positives. The whole-cell-based screening method was validated by screening
      site-saturation libraries of PAMO and resulted in the identification of PAMO
      mutants with altered catalytic properties. This new method can be used for
      screening libraries of BVMOs for activity with any desired substrate and
      therefore is a powerful tool for engineering of these enzymes. 

PMID- 23536547
TI  - Discovering new medicines targeting helicases: challenges and recent progress.
AB  - Helicases are ubiquitous motor proteins that separate and/or rearrange nucleic
      acid duplexes in reactions fueled by adenosine triphosphate (ATP) hydrolysis.
      Helicases encoded by bacteria, viruses, and human cells are widely studied
      targets for new antiviral, antibiotic, and anticancer drugs. This review
      summarizes the biochemistry of frequently targeted helicases. These proteins
      include viral enzymes from herpes simplex virus, papillomaviruses,
      polyomaviruses, coronaviruses, the hepatitis C virus, and various flaviviruses.
      Bacterial targets examined include DnaB-like and RecBCD-like helicases. The human
      DEAD-box protein DDX3 is the cellular antiviral target discussed, and cellular
      anticancer drug targets discussed are the human RecQ-like helicases and eIF4A. We
      also review assays used for helicase inhibitor discovery and the most promising
      and common helicase inhibitor chemotypes, such as nucleotide analogues,
      polyphenyls, metal ion chelators, flavones, polycyclic aromatic polymers,
      coumarins, and various DNA binding pharmacophores. Also discussed are common
      complications encountered while searching for potent helicase inhibitors and
      possible solutions for these problems. 

PMID- 23536549
TI  - Kinesin-1 and mitochondrial motility control by discrimination of structurally
      equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding
      protein 2.
AB  - The pleckstrin homology (PH) domain is a versatile fold that mediates a variety
      of protein-protein and protein-phosphatidylinositol lipid interactions. The Ran
      binding protein 2 (RanBP2) contains four interspersed Ran GTPase-binding domains
      (RBD(n = 1-4)) with close structural homology to the PH domain of Bruton's
      tyrosine kinase. The RBD2, kinesin-binding domain (KBD) and RBD3 comprise a
      tripartite domain (R2KR3) of RanBP2 that causes the unfolding, microtubule
      binding and biphasic activation of kinesin-1, a crucial anterograde motor of
      mitochondrial motility. However, the interplay between Ran GTPase and R2KR3 of
      RanBP2 in kinesin-1 activation and mitochondrial motility is elusive. We use
      structure-function, biochemical, kinetic and cell-based assays with time-lapse
      live-cell microscopy of over 260,000 mitochondrial-motility-related events to
      find mutually exclusive subdomains in RBD2 and RBD3 towards Ran GTPase binding,
      kinesin-1 activation and mitochondrial motility regulation. The RBD2 and RBD3
      exhibit Ran-GTP-independent, subdomain and stereochemical-dependent
      discrimination on the biphasic kinetics of kinesin-1 activation or regulation of
      mitochondrial motility. Further, KBD alone and R2KR3 stimulate and suppress,
      respectively, multiple biophysical parameters of mitochondrial motility. The
      regulation of the bidirectional transport of mitochondria by either KBD or R2KR3
      is highly coordinated, because their kinetic effects are accompanied always by
      changes in mitochondrial motile events of either transport polarity. These
      studies uncover novel roles in Ran GTPase-independent subdomains of RBD2 and
      RBD3, and KBD of RanBP2, that confer antagonizing and multi-modal mechanisms of
      kinesin-1 activation and regulation of mitochondrial motility. These findings
      open new venues towards the pharmacological harnessing of cooperative and
      competitive mechanisms regulating kinesins, RanBP2 or mitochondrial motility in
      disparate human disorders.

PMID- 23536551
TI  - Dynamic interplay of ParA with the polarity protein, Scy, coordinates the growth
      with chromosome segregation in Streptomyces coelicolor.
AB  - Prior to bacterial cell division, the ATP-dependent polymerization of the
      cytoskeletal protein, ParA, positions the newly replicated origin-proximal region
      of the chromosome by interacting with ParB complexes assembled on parS sites
      located close to the origin. During the formation of unigenomic spores from multi
      genomic aerial hyphae compartments of Streptomyces coelicolor, ParA is
      developmentally triggered to form filaments along the hyphae; this promotes the
      accurate and synchronized segregation of tens of chromosomes into prespore
      compartments. Here, we show that in addition to being a segregation protein, ParA
      also interacts with the polarity protein, Scy, which is a component of the tip
      organizing centre that controls tip growth. Scy recruits ParA to the hyphal tips
      and regulates ParA polymerization. These results are supported by the phenotype
      of a strain with a mutant form of ParA that uncouples ParA polymerization from
      Scy. We suggest that the ParA-Scy interaction coordinates the transition from
      hyphal elongation to sporulation.

PMID- 23536552
TI  - High-throughput tyrosine kinase activity profiling identifies FAK as a candidate
      therapeutic target in Ewing sarcoma.
AB  - Limited progress has been made in the treatment of advanced-stage pediatric solid
      tumors despite the accelerated pace of cancer discovery over the last decade.
      Tyrosine kinase inhibition is one tractable therapeutic modality for treating
      human malignancy. However, little is known about the kinases critical to the
      development or maintenance of many pediatric solid tumors such as Ewing sarcoma.
      Using a fluorescent, bead-based technology to profile activated tyrosine kinases,
      we identified focal adhesion kinase (FAK, PTK2) as a candidate target in Ewing
      sarcoma. FAK is a tyrosine kinase critical for cellular adhesion, growth, and
      survival. As such, it is a compelling target for cancer-based therapy. In this
      study, we have shown that FAK is highly phosphorylated in primary Ewing sarcoma
      tumor samples and that downregulation of FAK by short hairpin RNA and treatment
      with a FAK-selective kinase inhibitor, PF-562271, impaired growth and colony
      formation in Ewing sarcoma cell lines. Moreover, treatment of Ewing sarcoma cell
      lines with PF-562271 induced apoptosis and led to downregulation of AKT/mTOR and
      CAS activity. Finally, we showed that small-molecule inhibition of FAK attenuated
      Ewing sarcoma tumor growth in vivo. With FAK inhibitors currently in early-phase
      clinical trials for adult malignancies, these findings may bear immediate
      relevance to patients with Ewing sarcoma.

PMID- 23536550
TI  - Heterotrimeric G protein signalling in the plant kingdom.
AB  - In animals, heterotrimeric G proteins, comprising alpha-, beta-and gamma
      subunits, perceive extracellular stimuli through cell surface receptors, and
      transmit signals to ion channels, enzymes and other effector proteins to affect
      numerous cellular behaviours. In plants, G proteins have structural similarities
      to the corresponding molecules in animals but transmit signals by atypical
      mechanisms and effector proteins to control growth, cell proliferation, defence,
      stomate movements, channel regulation, sugar sensing and some hormonal responses.
      In this review, we summarize the current knowledge on the molecular regulation of
      plant G proteins, their effectors and the physiological functions studied mainly
      in two model organisms: Arabidopsis thaliana and rice (Oryza sativa). We also
      look at recent progress on structural analyses, systems biology and evolutionary
      studies.

PMID- 23536553
TI  - Oncogenic NRAS, required for pathogenesis of embryonic rhabdomyosarcoma, relies
      upon the HMGA2-IGF2BP2 pathway.
AB  - Embryonic rhabdomyosarcoma (ERMS) is the most common soft-tissue tumor in
      children. Here, we report the identification of the minor groove DNA-binding
      factor high mobility group AT-hook 2 (HMGA2) as a driver of ERMS development.
      HMGA2 was highly expressed in normal myoblasts and ERMS cells, where its
      expression was essential to maintain cell proliferation, survival in vitro, and
      tumor outgrowth in vivo. Mechanistic investigations revealed that upregulation of
      the insulin-like growth factor (IGF) mRNA-binding protein IGF2BP2 was critical
      for HMGA2 action. In particular, IGF2BP2 was essential for mRNA and protein
      stability of NRAS, a frequently mutated gene in ERMS. shRNA-mediated attenuation
      of NRAS or pharmacologic inhibition of the MAP-ERK kinase (MEK)/extracellular
      signal-regulated kinase (ERK) effector pathway showed that NRAS and NRAS-mediated
      signaling was required for tumor maintenance. Taken together, these findings
      implicate the HMGA2-IGFBP2-NRAS signaling pathway as a critical oncogenic driver
      in ERMS.

PMID- 23536554
TI  - Interleukin-1beta promotes skeletal colonization and progression of metastatic
      prostate cancer cells with neuroendocrine features.
AB  - Despite the progress made in the early detection and treatment of prostate
      adenocarcinoma, the metastatic lesions from this tumor are incurable. We used
      genome-wide expression analysis of human prostate cancer cells with different
      metastatic behavior in animal models to reveal that bone-tropic phenotypes
      upregulate three genes encoding for the cytokine interleukin-1beta (IL-1beta),
      the chemokine CXCL6 (GCP-2), and the protease inhibitor elafin (PI3). The
      Oncomine database revealed that these three genes are significantly upregulated
      in human prostate cancer versus normal tissue and correlate with Gleason scores
      >=7. This correlation was further validated for IL-1beta by immunodetection in
      prostate tissue arrays. Our study also shows that the exogenous overexpression of
      IL-1beta in nonmetastatic cancer cells promotes their growth into large skeletal
      lesions in mice, whereas its knockdown significantly impairs the bone progression
      of highly metastatic cells. In addition, IL-1beta secreted by metastatic cells
      induced the overexpression of COX-2 (PTGS2) in human bone mesenchymal cells
      treated with conditioned media from bone metastatic prostate cancer cells.
      Finally, we inspected human tissue specimens from skeletal metastases and
      detected prostate cancer cells positive for both IL-1beta and synaptophysin while
      concurrently lacking prostate-specific antigen (PSA, KLK3) expression.
      Collectively, these findings indicate that IL-1beta supports the skeletal
      colonization and metastatic progression of prostate cancer cells with an acquired
      neuroendocrine phenotype.

PMID- 23536555
TI  - Trop-2 promotes prostate cancer metastasis by modulating beta(1) integrin
      functions.
AB  - The molecular mechanisms underlying metastatic dissemination are still not
      completely understood. We have recently shown that beta(1) integrin-dependent
      cell adhesion to fibronectin and signaling is affected by a transmembrane
      molecule, Trop-2, which is frequently upregulated in human carcinomas. Here, we
      report that Trop-2 promotes metastatic dissemination of prostate cancer cells in
      vivo and is abundantly expressed in metastasis from human prostate cancer. We
      also show here that Trop-2 promotes prostate cancer cell migration on
      fibronectin, a phenomenon dependent on beta(1) integrins. Mechanistically, we
      demonstrate that Trop-2 and the alpha(5)beta(1) integrin associate through their
      extracellular domains, causing relocalization of alpha(5)beta(1) and the beta(1)
      associated molecule talin from focal adhesions to the leading edges. Trop-2
      effect is specific as this molecule does not modulate migration on vitronectin,
      does not associate with the major vitronectin receptor, alpha(v)beta(3) integrin,
      and does not affect localization of alpha(v)beta(3) integrin as well as vinculin
      in focal adhesions. We show that Trop-2 enhances directional prostate cancer cell
      migration, through modulation of Rac1 GTPase activity. Finally, we show that Trop
      2 induces activation of PAK4, a kinase that has been reported to mediate cancer
      cell migration. In conclusion, we provide the first evidence that beta(1)
      integrin-dependent migratory and metastatic competence of prostate cancer cells
      is enhanced by Trop-2.

PMID- 23536556
TI  - Myeloid-derived suppressor cells as a vehicle for tumor-specific oncolytic viral
      therapy.
AB  - One of the several impediments to effective oncolytic virus therapy of cancer
      remains a lack of tumor-specific targeting. Myeloid-derived suppressor cells
      (MDSC) are immature myeloid cells induced by tumor factors in tumor-bearing
      hosts. The biodistribution kinetics of MDSC and other immune cell types in a
      murine hepatic colon cancer model was investigated through the use of tracking
      markers and MRI. MDSCs were superior to other immune cell types in preferential
      migration to tumors in comparison with other tissues. On the basis of this
      observation, we engineered a strain of vesicular stomatitis virus (VSV), an
      oncolytic rhabdovirus that bound MDSCs and used them as a delivery vehicle.
      Improving VSV-binding efficiency to MDSCs extended the long-term survival of mice
      bearing metastatic colon tumors compared with systemic administration of wild
      type VSV alone. Survival was further extended by multiple injections of the
      engineered virus without significant toxicity. Notably, direct tumor killing was
      accentuated by promoting MDSC differentiation towards the classically activated
      M1-like phenotype. Our results offer a preclinical proof-of-concept for using
      MDSCs to facilitate and enhance the tumor-killing activity of tumor-targeted
      oncolytic therapeutics.

PMID- 23536558
TI  - ATF3 suppresses metastasis of bladder cancer by regulating gelsolin-mediated
      remodeling of the actin cytoskeleton.
AB  - Bladder cancer is associated with high recurrence and mortality rates due to
      metastasis. The elucidation of metastasis suppressors may offer therapeutic
      opportunities if their mechanisms of action can be elucidated and tractably
      exploited. In this study, we investigated the clinical and functional
      significance of the transcription factor activating transcription factor 3 (ATF3)
      in bladder cancer metastasis. Gene expression analysis revealed that decreased
      ATF3 was associated with bladder cancer progression and reduced survival of
      patients with bladder cancer. Correspondingly, ATF3 overexpression in highly
      metastatic bladder cancer cells decreased migration in vitro and experimental
      metastasis in vivo. Conversely, ATF3 silencing increased the migration of bladder
      cancer cells with limited metastatic capability in the absence of any effect on
      proliferation. In keeping with their increased motility, metastatic bladder
      cancer cells had increased numbers of actin filaments. Moreover, ATF3 expression
      correlated with expression of the actin filament severing protein gelsolin (GSN).
      Mechanistic studies revealed that ATF3 upregulated GSN, whereas ATF3 silencing
      reduced GSN levels, concomitant with alterations in the actin cytoskeleton. We
      identified six ATF3 regulatory elements in the first intron of the GSN gene
      confirmed by chromatin immunoprecipitation analysis. Critically, GSN expression
      reversed the metastatic capacity of bladder cancer cells with diminished levels
      of ATF3. Taken together, our results indicate that ATF3 suppresses metastasis of
      bladder cancer cells, at least in part through the upregulation of GSN-mediated
      actin remodeling. These findings suggest ATF3 coupled with GSN as prognostic
      markers for bladder cancer metastasis.

PMID- 23536557
TI  - Th-MYCN mice with caspase-8 deficiency develop advanced neuroblastoma with bone
      marrow metastasis.
AB  - Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible
      for 15% of all childhood cancer deaths. Patients frequently present at diagnosis
      with metastatic disease, particularly to the bone marrow. Advances in therapy and
      understanding of the metastatic process have been limited due, in part, to the
      lack of animal models harboring bone marrow disease. The widely used transgenic
      model, the Th-MYCN mouse, exhibits limited metastasis to this site. Here, we
      establish the first genetic immunocompetent mouse model for metastatic
      neuroblastoma with enhanced secondary tumors in the bone marrow. This model
      recapitulates 2 frequent alterations in metastatic neuroblastoma, overexpression
      of MYCN and loss of caspase-8 expression. Mouse caspase-8 gene was deleted in
      neural crest lineage cells by crossing a Th-Cre transgenic mouse with a caspase-8
      conditional knockout mouse. This mouse was then crossed with the neuroblastoma
      prone Th-MYCN mouse. Although overexpression of MYCN by itself rarely caused bone
      marrow metastasis, combining MYCN overexpression and caspase-8 deletion
      significantly enhanced bone marrow metastasis (37% incidence). Microarray
      expression studies of the primary tumors mRNAs and microRNAs revealed
      extracellular matrix structural changes, increased expression of genes involved
      in epithelial to mesenchymal transition, inflammation, and downregulation of miR
      7a and miR-29b. These molecular changes have been shown to be associated with
      tumor progression and activation of the cytokine TGF-beta pathway in various
      tumor models. Cytokine TGF-beta can preferentially promote single cell motility
      and blood-borne metastasis and therefore activation of this pathway may explain
      the enhanced bone marrow metastasis observed in this animal model.

PMID- 23536559
TI  - The 19th annual Prostate Cancer Foundation scientific retreat.
AB  - Prostate Cancer Foundation (PCF) convened its 19th Annual Scientific Retreat
      October 25-27, 2012, in Carlsbad, CA. Each year, this event brings together
      diverse researchers in a collaborative forum to present and discuss new and
      largely unpublished findings for prostate cancer diagnosis, prognosis, and
      treatment and defines the challenges to ending this disease as a threat to life
      and well-being. Several themes resonated at the multidisciplinary meeting,
      notably (i) the roles of field cancerization, tumor microenvironment, epithelial
      plasticity, signal transduction pathways in cancer progression, and disease
      resistance; (ii) intratumoral heterogeneity and consequences for precision
      medicine; (iii) resistance mechanisms to androgen axis inhibitors; and (iv)
      advances in molecular imaging and therapeutics for better detection and
      treatment.

PMID- 23536560
TI  - Tumor-immune dynamics regulated in the microenvironment inform the transient
      nature of immune-induced tumor dormancy.
AB  - Cancer in a host induces responses that increase the ability of the
      microenvironment to sustain the growing mass, for example, angiogenesis, but
      cancer cells can have varying sensitivities to these sustainability signals.
      Here, we show that these sensitivities are significant determinants of ultimate
      tumor fate, especially in response to treatments and immune interactions. We
      present a mathematical model of cancer-immune interactions that modifies
      generalized logistic growth with both immune-predation and immune-recruitment.
      The role of a growing environmental carrying capacity is discussed as a possible
      regulatory mechanism for tumor growth, and this regulation is shown to modify
      cancer-immune interactions and the possibility of achieving immune-induced tumor
      dormancy. This mathematical model qualitatively matches experimental observations
      of immune-induced tumor dormancy as it predicts dormancy as a transient period of
      growth that necessarily ends in either tumor elimination or tumor escape. As
      dormant tumors may exist asymptomatically and may be easier to treat with
      conventional therapy, an understanding of the mechanisms behind tumor dormancy
      may lead to new treatments aimed at prolonging the dormant state or converting an
      aggressive cancer to the dormant state.

PMID- 23536561
TI  - Common genetic polymorphisms modify the effect of smoking on absolute risk of
      bladder cancer.
AB  - Bladder cancer results from the combined effects of environmental and genetic
      factors, smoking being the strongest risk factor. Evaluating absolute risks
      resulting from the joint effects of smoking and genetic factors is critical to
      assess the public health relevance of genetic information. Analyses included up
      to 3,942 cases and 5,680 controls of European background in seven studies. We
      tested for multiplicative and additive interactions between smoking and 12
      susceptibility loci, individually and combined as a polygenic risk score (PRS).
      Thirty-year absolute risks and risk differences by levels of the PRS were
      estimated for U.S. males aged 50 years. Six of 12 variants showed significant
      additive gene-environment interactions, most notably NAT2 (P = 7 * 10(-4)) and
      UGT1A6 (P = 8 * 10(-4)). The 30-year absolute risk of bladder cancer in U.S.
      males was 6.2% for all current smokers. This risk ranged from 2.9% for current
      smokers in the lowest quartile of the PRS to 9.9% for current smokers in the
      upper quartile. Risk difference estimates indicated that 8,200 cases would be
      prevented if elimination of smoking occurred in 100,000 men in the upper PRS
      quartile compared with 2,000 cases prevented by a similar effort in the lowest
      PRS quartile (P(additive) = 1 * 10(-4)). Thus, the potential impact of
      eliminating smoking on the number of bladder cancer cases prevented is larger for
      individuals at higher than lower genetic risk. Our findings could have
      implications for targeted prevention strategies. However, other smoking-related
      diseases, as well as practical and ethical considerations, need to be considered
      before any recommendations could be made.

PMID- 23536562
TI  - Genetic susceptibility to triple-negative breast cancer.
AB  - Triple-negative breast cancers (TNBC), defined by the absence of estrogen
      receptor, progesterone receptor, and HER-2 expression, account for 12% to 24% of
      all breast cancers. TNBC is associated with early recurrence of disease and poor
      outcome. Germline mutations in the BRCA1 and BRCA2 breast cancer susceptibility
      genes have been associated with up to 15% of TNBC, and TNBC accounts for 70% of
      breast tumors arising in BRCA1 mutation carriers and 16% to 23% of breast tumors
      in BRCA2 carriers. Whether germline mutations in other breast cancer
      susceptibility genes also predispose to TNBC remains to be determined. Common
      variation in a subset of the 72 known breast cancer susceptibility loci
      identified through genome-wide association studies and other large-scale
      genotyping efforts have also been associated with risk of TNBC (TOX3, ESR1,
      RAD51L1, TERT, 19p13.1, 20q11, MDM4, 2p24.1, and FTO). Furthermore, variation in
      the 19p13.1 locus and the MDM4 locus has been associated with TNBC, but not other
      forms of breast cancer, suggesting that these are TNBC-specific loci. Thus, TNBC
      can be distinguished from other breast cancer subtypes by a unique pattern of
      common and rare germline predisposition alleles. Additional efforts to combine
      genetic and epidemiologic data are needed to better understand the etiology of
      this aggressive form of breast cancer, to identify prevention and therapeutic
      targets, and to impact clinical practice through the development of risk
      prediction models.

PMID- 23536564
TI  - The multifaceted role of the microenvironment in liver metastasis: biology and
      clinical implications.
AB  - The liver is host to many metastatic cancers, particularly colorectal cancer, for
      which the last 2 decades have seen major advances in diagnosis and treatment. The
      liver is a vital organ, and the extent of its involvement with metastatic disease
      is a major determinant of survival. Metastatic cells arriving in the liver via
      the bloodstream encounter the microenvironment of the hepatic sinusoid. The
      interactions of the tumor cells with hepatic sinusoidal and extrasinusoidal cells
      (endothelial, Kupffer, stellate, and inflammatory cells) determine their fate.
      The sinusoidal cells can have a dual role, sometimes fatal to the tumor cells but
      also facilitatory to their survival and growth. Adhesion molecules participate in
      these interactions and may affect their outcome. Bone marrow-derived cells and
      chemokines also play a part in the early battle for survival of the metastases.
      Once the tumor cells have arrested and survived the initial onslaught, tumors can
      grow within the liver in 3 distinct patterns, reflecting differing host
      responses, mechanisms of vascularization, and proteolytic activity. This review
      aims to present current knowledge of the interactions between the host liver
      cells and the invading metastases that has implications for the clinical course
      of the disease and the response to treatment.

PMID- 23536563
TI  - Loss of TGF-beta adaptor beta2SP activates notch signaling and SOX9 expression in
      esophageal adenocarcinoma.
AB  - TGF-beta and Notch signaling pathways play important roles in regulating self
      renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-beta
      signaling components activates Notch signaling in esophageal adenocarcinoma, but
      the basis for this effect has been unclear. Here we report that loss of TGF-beta
      adapter beta2SP (SPNB2) activates Notch signaling and its target SOX9 in primary
      fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell
      marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than
      normal tissues, and its higher nuclear staining in tumors correlated with poorer
      survival and lymph node invasion in esophageal adenocarcinoma patients.
      Downregulation of beta2SP by lentivirus short hairpin RNA increased SOX9
      transcription and expression, enhancing nuclear localization for both active
      Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into
      esophageal adenocarcinoma cells of beta2SP and a dominant-negative mutant of the
      Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor
      sphere formation and invasive capacity in vitro and tumor growth in vivo were
      increased in beta2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9
      silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of
      beta2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also
      observed, with loss of beta2SP increasing the binding between these proteins,
      inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of
      TGF-beta targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our
      findings suggest that loss of beta2SP switches TGF-beta signaling from tumor
      suppression to tumor promotion by engaging Notch signaling and activating SOX9.

PMID- 23536565
TI  - Extramacrochaetae imposes order on the Drosophila eye by refining the activity of
      the Hedgehog signaling gradient.
AB  - The compound eye of Drosophila melanogaster is configured by a differentiating
      wave, the morphogenetic furrow, that sweeps across the eye imaginal disc and
      transforms thousands of undifferentiated cells into a precisely ordered
      repetitive array of 800 ommatidia. The initiation of the furrow at the posterior
      margin of the epithelium and its subsequent movement across the eye field is
      controlled by the activity of the Hedgehog (Hh) signaling pathway.
      Differentiating photoreceptors that lie behind the furrow produce and secrete the
      Hh morphogen, which is captured by cells within the furrow itself. This leads to
      the stabilization of the full-length form of the zinc-finger transcription factor
      Cubitus interruptus (Ci(155)), the main effector of Hh signaling. Ci(155)
      functions as a transcriptional activator of a number of downstream targets,
      including decapentaplegic (dpp), a TGFbeta homolog. In this report, we describe a
      mechanism that is in place within the fly retina to limit Hh pathway activity
      within and ahead of the furrow. We demonstrate that the helix-loop-helix (HLH)
      protein Extramacrochaetae (Emc) regulates Ci(155) levels. Loss of emc leads to an
      increase in Ci(155) levels, nuclear migration, apical cell constriction and an
      acceleration of the furrow. We find that these roles are distinct from the bHLH
      protein Hairy (H), which we show restricts atonal (ato) expression ahead of the
      furrow. Secondary furrow initiation along the dorsal and ventral margins is
      blocked by the activity of the Wingless (Wg) pathway. We also show that Emc
      regulates and cooperates with Wg signaling to inhibit lateral furrow initiation.

PMID- 23536566
TI  - Anteroposterior and dorsoventral patterning are coordinated by an identical
      patterning clock.
AB  - Establishment of the body plan in vertebrates depends on the temporally
      coordinated patterning of tissues along the body axes. We have previously shown
      that dorsoventral (DV) tissues are temporally patterned progressively from
      anterior to posterior by a BMP signaling pathway. Here we report that DV
      patterning along the zebrafish anteroposterior (AP) axis is temporally
      coordinated with AP patterning by an identical patterning clock. We altered AP
      patterning by inhibiting or activating FGF, Wnt or retinoic acid signaling
      combined with inhibition of BMP signaling at a series of developmental time
      points, which revealed that the temporal progression of DV patterning is directly
      coordinated with AP patterning. We investigated how these signaling pathways are
      integrated and suggest a model for how DV and AP patterning are temporally
      coordinated. It has been shown that in Xenopus dorsal tissues FGF and Wnt
      signaling quell BMP signaling by degrading phosphorylated (P) Smad1/5, the BMP
      pathway signal transducer, via phosphorylation of the Smad1/5 linker region. We
      show that in zebrafish FGF/MAPK, but not Wnt/GSK3, phosphorylation of the Smad1/5
      linker region localizes to a ventral vegetal gastrula region that could
      coordinate DV patterning with AP patterning ventrally without degrading P
      Smad1/5. Furthermore, we demonstrate that alteration of the MAPK phosphorylation
      sites in the Smad5 linker causes precocious patterning of DV tissues along the AP
      axis during gastrulation. Thus, DV and AP patterning are intimately coordinated
      to allow cells to acquire both positional and temporal information
      simultaneously.

PMID- 23536567
TI  - The secreted AdamTS-A metalloprotease is required for collective cell migration.
AB  - Members of the ADAMTS family of secreted metalloproteases play crucial roles in
      modulating the extracellular matrix (ECM) in development and disease. Here, we
      show that ADAMTS-A, the Drosophila ortholog of human ADAMTS 9 and ADAMTS 20, and
      of C. elegans GON-1, is required for cell migration during embryogenesis. AdamTS
      A is expressed in multiple migratory cell types, including hemocytes, caudal
      visceral mesoderm (CVM), the visceral branch of the trachea (VBs) and the
      secretory portion of the salivary gland (SG). Loss of AdamTS-A causes defects in
      germ cell, CVM and VB migration and, depending on the tissue, AdamTS-A functions
      both autonomously and non-autonomously. In the highly polarized collective of the
      SG epithelium, loss of AdamTS-A causes apical surface irregularities and cell
      elongation defects. We provide evidence that ADAMTS-A is secreted into the SG
      lumen where it functions to release cells from the apical ECM, consistent with
      the defects observed in AdamTS-A mutant SGs. We show that loss of the apically
      localized protocadherin Cad99C rescues the SG defects, suggesting that Cad99C
      serves as a link between the SG apical membrane and the secreted apical ECM
      component(s) cleaved by ADAMTS-A. Our analysis of AdamTS-A function in the SG
      suggests a novel role for ADAMTS proteins in detaching cells from the apical ECM,
      facilitating tube elongation during collective cell migration.

PMID- 23536568
TI  - PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain
      polarity in the C. elegans embryo.
AB  - In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism
      between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the
      posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The
      mechanisms by which these proteins interact to maintain polarity are incompletely
      understood. In this study, we investigate the interplay among PAR-2, LGL-1,
      myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect
      cortical myosin accumulation by different mechanisms. LGL-1 does not directly
      antagonize the accumulation of cortical myosin and instead plays a role in
      regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in
      regulating cortical myosin accumulation and preventing the expansion of the
      anterior cortical domain. We also provide evidence that asymmetry of active CDC
      42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that
      includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary
      role in regulating the size of the anterior cortical domain via its binding to
      PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not
      dependent on PAR-6.

PMID- 23536569
TI  - Dual role for Hox genes and Hox co-factors in conferring leg motoneuron survival
      and identity in Drosophila.
AB  - Adult Drosophila walk using six multi-jointed legs, each controlled by ~50 leg
      motoneurons (MNs). Although MNs have stereotyped morphologies, little is known
      about how they are specified. Here, we describe the function of Hox genes and
      homothorax (hth), which encodes a Hox co-factor, in Drosophila leg MN
      development. Removing either Hox or Hth function from a single neuroblast (NB)
      lineage results in MN apoptosis. A single Hox gene, Antennapedia (Antp), is
      primarily responsible for MN survival in all three thoracic segments. When cell
      death is blocked, partially penetrant axon branching errors are observed in Hox
      mutant MNs. When single MNs are mutant, errors in both dendritic and axon
      arborizations are observed. Our data also suggest that Antp levels in post
      mitotic MNs are important for specifying their identities. Thus, in addition to
      being essential for survival, Hox and hth are required to specify accurate MN
      morphologies in a level-dependent manner.

PMID- 23536570
TI  - Embryonic stem cell-derived granulosa cells participate in ovarian follicle
      formation in vitro and in vivo.
AB  - Differentiating embryonic stem cells (ESCs) can form ovarian follicle-like
      structures in vitro, consisting of an oocyte-like cell surrounded by somatic
      cells capable of steroidogenesis. Using a dual-fluorescence reporter system in
      which mouse ESCs express green fluorescent protein (GFP) under the control of a
      germ cell-specific Pou5f1 gene promoter and red fluorescent protein (Discosoma sp
      red [DsRed]) driven by the granulosa cell-specific Forkhead box L2 (Foxl2) gene
      promoter, we first confirmed in vitro formation of follicle-like structures
      containing GFP-positive cells surrounded by DsRed-positive cells. Isolated DsRed
      positive cells specified from ECSs exhibited a gene expression profile consistent
      with granulosa cells, as revealed by the detection of messenger RNAs (mRNAs) for
      Foxl2, follistatin (Fst), anti-Mullerian hormone (Amh), and follicle-stimulating
      hormone receptor (Fshr) as well as by production of both progesterone and
      estradiol. In addition, treatment of isolated DsRed-expressing cells with
      follicle-stimulating hormone (FSH) significantly increased estradiol production
      over basal levels, confirming the presence of functional FSH receptors in these
      cells. Last, ESC-derived DsRed-positive cells injected into neonatal mouse
      ovaries became incorporated within the granulosa cell layer of immature
      follicles. These studies demonstrate that Foxl2-expressing ovarian somatic cells
      derived in vitro from differentiating ESCs express granulosa cell markers,
      actively associate with germ cells in vitro, synthesize steroids, respond to FSH,
      and participate in folliculogenesis in vivo.

PMID- 23536571
TI  - Regression of endometrial implants by resveratrol in an experimentally induced
      endometriosis model in rats.
AB  - OBJECTIVE: To evaluate the effect of resveratrol on an experimentally induced
      endometriosis rat model. STUDY DESIGN: After endometriotic implants were
      surgically formed, rats were randomly divided into 2 groups as control group
      (saline treated, n = 6) and resveratrol group (10 mg/kg/d, n = 6). The
      inflammatory markers and histopathological changes were assessed at the end of
      the treatment period. Results Our results showed (1) significant reduction in the
      implant size (P < .0005); (2) significantly decreased levels of vascular
      endothelial growth factor (VEGF) in the peritoneal fluid and plasma (P < .005);
      and monocyte chemotactic protein 1 (MCP-1) in the peritoneal fluid (P < .05), (3)
      highly significant suppression of VEGF expression in the endometriotic tissue (P
      < .0005); and (4) considerable histological changes in the endometriotic foci
      following resveratrol treatment. CONCLUSION: Resveratrol appears to be effective
      on the development of endometriosis through its antiangiogenic and anti
      inflammatory properties. Future studies with different doses of resveratrol might
      provide more comprehensive results regarding the treatment of endometriosis.

PMID- 23536572
TI  - Spindle and chromosomal alterations in metaphase II oocytes.
AB  - The spindle apparatus is a vital structure and must be structurally intact for
      proper segregation of the oocyte's genetic material during metaphase II.
      Endometriosis, oxidative stress, and cryopreservation can all adversely affect
      the structural integrity of the spindle, potentially resulting in aneuploidy and
      spontaneous abortion of the embryo. Advances in spindle imagery have made it
      possible to visualize the effects of environmental stresses on spindle structure.
      Deviation from an oocyte's normal environment can seriously impair the
      positioning and integrity of the spindle. Oocytes cryopreservation causes
      depolymerization and repolymerization of the spindle. Oocytes can also be
      preserved in an immature state for later in vitro maturation. A comprehensive
      understanding of the spindle behavior is paramount for the effective manipulation
      of oocytes in an assisted reproductive setting. 

PMID- 23536573
TI  - Therapeutic potential of Wenshen Xiaozheng tang, a traditional Chinese medicine
      prescription, for treating endometriosis.
AB  - The objective of this study is to investigate the effect of Wenshen Xiaozheng
      Tang (WXT) on the development of endometriosis in a rat model. Sprague-Dawley
      rats in which endometriotic implants were induced were divided randomly into 3
      groups. The rats in the low-dose and high-dose WXT groups were administered WXT
      8.57 and 17.14 g/kg/d, respectively. The rats in the control groups received an
      equal volume of dissolvent, as did the sham-operated rats. After treatment for 4
      weeks, WXT significantly decreased the mean lesion size as well as the peritoneal
      fluid and serum levels of tumor necrosis factor alpha and interleukin 1beta.
      Cyclooxygenase-2, matrix metalloproteinase 9, plasminogen activator inhibitor 1,
      and intercellular adhesion molecule 1 messenger RNA (mRNA) levels were
      downregulated, and the mRNA expression of tissue inhibitor of metalloproteinase 1
      was upregulated in the endometriotic lesions of WXT versus control group. Our
      data suggested that WXT may suppress the development of endometriosis by
      inhibiting the production of proinflammatory cytokines and regulating the
      expression of invasion-related genes in the endometriotic lesions. 

PMID- 23536574
TI  - The chorion layer of fetal membranes is prematurely destroyed in women with
      preterm premature rupture of the membranes.
AB  - Preterm premature rupture of the membranes (PPROM) is an important etiology of
      preterm birth and source of significant neonatal morbidity. We propose that PPROM
      occurs in the setting of long-standing altered tissue remodeling, which creates a
      vulnerable environment for the fetal membranes and pregnancy. We tested the
      hypothesis that PPROM is the result of tissue remodeling in the fetal membranes,
      specifically the chorion, and this weakening of the chorion compromises the
      protection provided to the amnion. The purpose of this study was to quantify
      thickness and apoptosis in the choriodecidua of fetal membranes in patients with
      PPROM, preterm labor (PTL), preterm no labor (PTNL), and women with term labor
      (TERM). We conducted a retrospective evaluation of fetal membrane samples from 86
      placentas. Immunohistochemistry was performed using a cytokeratin antibody, and
      mean chorion cellular thickness was compared between each clinical group. To
      evaluate chorion apoptosis, fetal membranes from patients with PPROM, PTL, and
      TERM were stained with the M30 antibody, and the degree of cellular apoptosis was
      determined. Statistical analysis was performed using analysis of variance with
      corrections for multiple comparisons. The chorion cellular layer was thinner in
      patients with PPROM compared to patients with PTNL and TERM (62, 140, and 169 um,
      respectively, P < .0001), though not significantly different from PTL (95 um, P >
      .05). The percentage of apoptotic cells within the chorion among the patients
      with PPROM was greater compared to PTL and TERM (24.2%, 13.1%, and 8.4%,
      respectively, P < .001). The chorion cellular layer is thinner and demonstrates
      increased apoptosis in PPROM compared to patients with PTL, PTNL, and TERM,
      suggesting differential remodeling between clinical phenotypes. 

PMID- 23536575
TI  - The effects of ranibizumab on surgically induced endometriosis in a rat model: a
      preliminary study.
AB  - OBJECTIVE: To examine the effect of ranibizumab on surgically induced
      endometriosis in rat models. STUDY DESIGN: Endometrial tissue was implanted onto
      the abdominal peritoneum of 20 rats that were randomized into 2 groups. The rats
      in group 1 (n = 9) were given 0.6 mg/kg ranibizumab on the 1st and 14th days
      after the second operation. The rats in group 2 (control group, n = 9) received
      no medication. All the rats were observed for a total of 28 days. RESULTS: At the
      end of the treatment, the mean volume and weight of the explants in group 1
      (11.49 +/- 6.87 mm(3) and 36.61 +/- 17.84 mg) were significantly lower than that
      of the control group (190.6 +/- 177.4 mm(3) and 187.3 +/- 174.5 mg; both Ps <
      .01). Mean epithelial histologic scores were significantly lower in group 1 (1.11
      +/- 0.78) than that of the control group (2.33 +/- 0.71; P < .01). When compared
      with the control group, vascular endothelial growth factor (VEGF)
      immunoreactivities in group 1 showed statistically significant reductions (1.67
      +/- 0.50; 2.67 +/- 0.50; P < .01). CONCLUSION: Ranibizumab has significantly
      regressed the size of the endometriotic implants and caused atrophy of these
      lesions in rats by decreasing explant levels of VEGF.

PMID- 23536576
TI  - Risk prediction of esophageal squamous-cell carcinoma with common genetic
      variants and lifestyle factors in Chinese population.
AB  - Genome-wide association studies have identified multiple genetic variants
      associated with risk of esophageal squamous-cell carcinoma (ESCC) in Chinese
      populations. We examined whether these genetic factors, along with non-genetic
      factors, can contribute to ESCC risk prediction. We examined 25 single nucleotide
      polymorphisms (SNPs) and 4 non-genetic factors (sex, age, smoking and drinking)
      associated with ESCC risk in 9805 cases and 10 493 controls from Chinese
      populations. Weighted genetic risk score (wGRS) was calculated and logistic
      regression was used to analyze the association between wGRS and ESCC risk. We
      calculated the area under the curve (AUC) using receiver operating characteristic
      curve analysis to measure the discrimination after adding genetic variants to the
      model with only non-genetic factors. Net reclassification improvement (NRI) was
      used to quantify the degree of correct reclassification using different models.
      wGRS of the combined 17 SNPs with significant marginal effect (G SNPs) increased
      ~4-fold ESCC risk (P = 1.49 * 10(-) (164)) and the associations were significant
      in both drinkers and non-drinkers. However, wGRS of the eight SNPs with
      significant effect in gene * drinking interaction (GE SNPs) increased ~4-fold
      ESCC risk only in drinkers (P interaction = 8.76 * 10(-) (41)). The AUC for a
      risk model with 4 non-genetic factors, 17 G SNPs, 8 GE SNPs and their
      interactions with drinking was 70.1%, with the significant improvement of 7.0%
      compared with the model with only non-genetic factors (P < 0.0001). Our results
      indicate that incorporating genetic variants, lifestyle factors and their
      interactions in ESCC risk models can be useful for identifying patients with
      ESCC. 

PMID- 23536577
TI  - Undifferentiated embryonic cell transcription factor-1 (UTF1) inhibits the growth
      of cervical cancer cells by transactivating p27Kip1.
AB  - Undifferentiated embryonic cell transcription factor-1 (UTF1) is an important
      transcription factor during development, which plays critical roles in cell fate
      determination. However, its expression and function in somatic tissues remain
      unclear. Here, we investigated the expression pattern of the UTF1 in the human
      normal and cancerous lesions of cervix and found that UTF1 was downregulated in
      cervical carcinogenesis, which was related to the hypermethylation of UTF1
      promoter. Exogenous expression of UTF1 resulted in the significant inhibition of
      cell proliferation in vitro and tumorigenesis in vivo through attenuating cell
      cycle arrest via increasing the level of p27 (Kip1) . Luciferase reporter assay
      indicated that the region containing an intact activating transcription factor
      site between nucleotides -517 and -388 of the p27 (Kip1) promoter was
      indispensable for its activation by UTF1. Chromatin immunoprecipitation analysis
      confirmed the physical interaction between UTF1 and the p27 (Kip1) promoter.
      Taken together, our findings reveal that UTF1 attenuates cell proliferation and
      is inactivated in cervical carcinogenesis through epigenetic modification, which
      strongly supports that UTF1 is a potential tumor suppressor. 

PMID- 23536579
TI  - HBxAPalpha/Rsf-1-mediated HBx-hBubR1 interactions regulate the mitotic spindle
      checkpoint and chromosome instability.
AB  - Hepatitis B virus (HBV) X protein (HBx), encoded by the HBV genome, is involved
      in the development of HBV-mediated liver cancer, whose frequency is highly
      correlated with chromosomal instability (CIN). We reported previously that HBx
      induces mitotic checkpoint dysfunction by targeting the human serine/threonine
      kinase BubR1 (hBubR1). However, the underlying mechanism remained unresolved.
      Here, we show that HBx protein-associated protein alpha (HBxAPalpha)/Rsf-1
      associates with hBubR1 and HBx in the chromatin fraction during mitosis.
      Depletion of HBxAPalpha/Rsf-1 abolished the interaction between HBx and hBubR1,
      indicating that HBxAPalpha/Rsf-1 mediates these interactions. Knockdown of
      HBxAPalpha/Rsf-1 with small interfering RNA did not affect the recruitment of
      hBubR1 to kinetochores; however, it did significantly impair HBx targeting to
      kinetochores. A deletion mutant analysis revealed that two Kunitz domains of HBx,
      the Cdc20-binding domain of hBubR1 and full-length of HBxAPalpha/Rsf-1 were
      essential for these interactions. Thus, binding of HBx to hBubR1, stabilized by
      HBxAPalpha/Rsf-1, significantly attenuated hBubR1 binding to Cdc20 and
      consequently increased the rate of mitotic aberrations. Collectively, our data
      show that the HBx impairs hBubR1 function and induces CIN through HBxAPalpha/Rsf
      1, providing a novel mechanism for induction of genomic instability by a viral
      pathogen in hepatocarcinogenesis. 

PMID- 23536578
TI  - Nanog expression is negatively regulated by protein kinase C activities in human
      cancer cell lines.
AB  - Nanog is a transcription factor that is essential for the maintenance of
      pluripotency of the embryonic stem cells. Nanog has been shown to be expressed in
      various kinds of human tumors, suggesting a role in tumorigenesis. In this study,
      we found that Nanog expression was upregulated by inhibition of protein kinase C
      (PKC) activity in six human cancer cell lines examined. In a Nanog non-expressing
      human nasopharyngeal carcinoma cell line, NPC-076, Nanog mRNA level and protein
      level were both induced and dose-dependently promoted by exposure to PKC
      inhibitors. Knockdown experiments showed that PKCalpha and PKCdelta were two
      subtypes exerted most of the effect. The reporter assay showed that Nanog
      promoter activity was promoted by exposure of the cells to PKC inhibitors and the
      effect was dependent on the presence of the Octamer-Sox composite element. The
      involvement of Octamer-Sox composite element was further supported by the
      observation that silencing of Oct4 and Sox2 in NPC-076 cells attenuated the
      effects of PKC inhibitors. In Nanog-expressing human embryonal carcinoma cell
      lines, NT2/D1 and NCCIT, Nanog expression was suppressed by exposure to PKC
      activator Phorbol-12-myristate-13-acetate (PMA). Further study showed that
      overexpression of PKCalpha elicited a repressive effect on Nanog expression in
      NT2/D1 cells. Consistently, mutation of the Octamer-Sox composite element
      abolished the suppressive effect by PKC activator. Nanog expression was of
      cellular significance in that ectopic expression in NPC-076 stimulated cell
      proliferation and knockdown of the endogenous Nanog expression in NT2/D1
      suppressed cell proliferation. 

PMID- 23536580
TI  - CCN3 promotes prostate cancer bone metastasis by modulating the tumor-bone
      microenvironment through RANKL-dependent pathway.
AB  - Bone metastasis in patient with advanced-stage prostate cancer, the most commonly
      diagnosed malignancy in Western countries, increases the risk of intractable bone
      pain. The nephroblastoma overexpressed (NOV/CCN3) gene, a member of the CCN gene
      family, is responsible for the secretion of CCN3, a matrix-associated protein
      involved in many cellular functions. However, the role of CCN3 in prostate cancer
      metastasis to bone is poorly understood. CCN3 was found to be highly expressed in
      bone metastasis patients and positively correlated with malignancy in human
      prostate cancer cells. Prostate cancer conditioned medium-induced osteoclast
      differentiation was inhibited by neutralizing antibody against CCN3.
      Specifically, CCN3 was found to induce osteoclastogenesis through the receptor
      activator of NF-kappaB ligand (RANKL)-dependent pathway, and the focal adhesion
      kinase/Akt/p38/NF-kappaB signal pathway was found to be involved in CCN3-mediated
      receptor activator of NF-kappaB expression and RANKL-dependent
      osteoclastogenesis. In contrast, osteoblasts were observed to play an important
      role in osteoclast differentiation by paracrine manner, with treatment of
      osteoblasts with CCN3 found to change the RANKL (osteoclastogenesis):OPG
      (antiosteoclastogenesis) ratio. Compared with parental PC3 cells, highly invasive
      PC3-I3 cells markedly enhanced osteoclast activity and bone metastasis in vivo.
      These results indicate that CCN3 can be used as a novel therapeutic target in the
      prevention of bone metastasis of prostate cancer. 

PMID- 23536581
TI  - Type 2 diabetes and risk of rupture of saccular intracranial aneurysm in eastern
      Finland.
AB  - OBJECTIVE: Type 2 diabetes is a risk factor for other forms of stroke, but its
      association with subarachnoid hemorrhage (SAH) from ruptured saccular
      intracranial aneurysm (sIA) has remained unclear. RESEARCH DESIGN AND METHODS:
      Kuopio Intracranial Aneurysm Database (www.uef.fi/ns) includes all ruptured and
      unruptured sIA cases from a defined catchment population in eastern Finland since
      1980. We compared the age-adjusted incidences of type 2 diabetes in 1,058
      ruptured and 484 unruptured sIA patients during 1994-2008, using the national
      registry of prescribed medicine purchases. RESULTS: Of the 1,058 ruptured sIA
      patients, 43% were males and 57% females, with a median age at rupture of 51 and
      56 years, respectively. From 1994 to 2008 or until death, 9% had been prescribed
      antidiabetes medication (ADM) with a median starting age of 58 years for males
      and 66 years for females. Of the 484 unruptured sIA patients, 44% were males and
      56% females, with a median age at the diagnosis of 53 and 55 years, respectively,
      and 9% had used ADM, with a median starting age of 61 years for males and 66
      years for females. The incidence of type 2 diabetes was highest in the age-group
      60-70 years, with no significant differences between the ruptured and unruptured
      sIA patients. CONCLUSIONS: Our study suggests that type 2 diabetes does not
      increase the risk of rupture of sIA, which is by far the most frequent cause of
      nontraumatic SAH.

PMID- 23536582
TI  - Fasting plasma glucose at 24-28 weeks to screen for gestational diabetes
      mellitus: new evidence from China.
AB  - OBJECTIVE: To evaluate the usefulness of a fasting plasma glucose (FPG) at 24-28
      weeks' gestation to screen for gestational diabetes mellitus (GDM). RESEARCH
      DESIGN AND METHODS: The medical records and results of a 75-g 2-h oral glucose
      tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending
      prenatal clinics in 15 hospitals in China were examined. RESULTS: FPG cutoff
      value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff
      value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this
      cutoff point, 12.2% of patients with mild GDM will be missed. The positive
      predictive value is 0.322, and the negative predictive value is 0.928.
      CONCLUSIONS: FPG at 24-28 weeks' gestation could be used as a screening test to
      identify GDM patients in low-resource regions. Women with an FPG between >=4.4
      and <=5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to
      avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.

PMID- 23536583
TI  - The effect of intensive glucose lowering on lipoprotein particle profiles and
      inflammatory markers in the Veterans Affairs Diabetes Trial (VADT).
AB  - OBJECTIVE: Intensive glucose-lowering therapy (INT) did not reduce macrovascular
      events in the recent randomized trials, possibly because it did not improve or
      worsen other traditional or novel cardiovascular risk factors. RESEARCH DESIGN
      AND METHODS: Standard plasma lipids, cholesterol content of lipoprotein
      subfractions, and plasma inflammatory and prothrombotic markers were determined
      in a subgroup of the Veterans Affairs Diabetes Trial (VADT) participants (n =
      266) at baseline and after 9 months of INT or standard therapy. RESULTS: INT
      lowered glycated hemoglobin (by a median of 2% vs. a median of 0.7% by standard
      treatment; P < 0.0001); increased BMI (4 vs. 1%; P < 0.001), total HDL (9 vs. 4%;
      P < 0.05), HDL2 (14 vs. 0%; P = 0.009), LDL2 (36 vs. 1%; P < 0.0001), and plasma
      adiponectin (130 vs. 80%; P < 0.01); and reduced triglycerides (-13 vs. -4%; P =
      0.02) and small, dense LDL4 (-39 vs. -13%; P < 0.001), but had no effect on
      levels of plasma apolipoproteins B-100 and B-48, C-reactive protein, interleukin
      6, lipoprotein-associated phospholipase A2, myeloperoxidase, fibrinogen, and
      plasminogen activator inhibitor 1. Incident macrovascular events were associated
      with baseline interleukin-6 (hazard ratio per each quartile increase 1.33 [95% CI
      1.06-1.66]), total LDL (1.25 [1.01-1.55]), apolipoprotein B-100 (1.29 [1.01
      1.65]), and fibrinogen (1.26 [1.01-1.57]) but not changes in any cardiovascular
      risk factors at 9 months. CONCLUSIONS: INT was associated with improved
      adiponectin, lipid levels, and a favorable shift in LDL and HDL subfractions
      after 9 months. These data suggest that the failure of INT to lower
      cardiovascular outcomes occurred despite generally favorable changes in standard
      and novel risk factors early in the study.

PMID- 23536584
TI  - Efficacy and safety of lixisenatide once-daily morning or evening injections in
      type 2 diabetes inadequately controlled on metformin (GetGoal-M).
AB  - OBJECTIVE: To examine the efficacy and safety of lixisenatide (20 MUg once daily,
      administered before the morning or evening meal) as add-on therapy in patients
      with type 2 diabetes insufficiently controlled with metformin alone. RESEARCH
      DESIGN AND METHODS: This was a 24-week, randomized, double-blind, placebo
      controlled study in 680 patients with inadequately controlled type 2 diabetes
      (HbA1c 7-10% [53-86 mmol/mol]). Patients were randomized to lixisenatide morning
      (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo
      evening (n = 85) injections. RESULTS: Lixisenatide morning injection
      significantly reduced mean HbA1c versus combined placebo (mean change -0.9% [9.8
      mmol/mol] vs. -0.4% [4.4 mmol/mol]; least squares [LS] mean difference vs.
      placebo -0.5% [5.5 mmol/mol], P < 0.0001). HbA1c was significantly reduced by
      lixisenatide evening injection (mean change -0.8% [8.7 mmol/mol] vs. -0.4% [4.4
      mmol/mol]; LS mean difference -0.4% [4.4 mmol/mol], P < 0.0001). Lixisenatide
      morning injection significantly reduced 2-h postprandial glucose versus morning
      placebo (mean change -5.9 vs. -1.4 mmol/L; LS mean difference -4.5 mmol/L, P <
      0.0001). LS mean difference in fasting plasma glucose was significant in both
      morning (-0.9 mmol/L, P < 0.0001) and evening (-0.6 mmol/L, P = 0.0046) groups
      versus placebo. Mean body weight decreased to a similar extent in all groups.
      Rates of adverse events were 69.4% in both lixisenatide groups and 60.0% in the
      placebo group. Rates for nausea and vomiting were 22.7 and 9.4% for lixisenatide
      morning and 21.2 and 13.3% for lixisenatide evening versus 7.6 and 2.9% for
      placebo, respectively. Symptomatic hypoglycemia occurred in 6, 13, and 1 patient
      for lixisenatide morning, evening, and placebo, respectively, with no severe
      episodes. CONCLUSIONS: In patients with type 2 diabetes inadequately controlled
      on metformin, lixisenatide 20 MUg once daily administered in the morning or
      evening significantly improved glycemic control, with a pronounced postprandial
      effect, and was well tolerated.

PMID- 23536585
TI  - Effects of a single bout of interval hypoxia on cardiorespiratory control and
      blood glucose in patients with type 2 diabetes.
AB  - OBJECTIVE: Hypoxia may cause functional autonomic imbalance in diabetes.
      Intermittent hypoxia (IH), a technique improving the adaptation to hypoxia, might
      improve cardiorespiratory reflexes and, ultimately, blood glucose concentrations
      in patients with type 2 diabetes. We tested whether a single bout of IH could
      initiate a long-lasting response potentially leading to better adaptation to
      hypoxia. RESEARCH DESIGN AND METHODS: In 14 patients with type 2 diabetes without
      autonomic complications, we measured blood pressure, heart rate, oxygen
      saturation, chemoreflex (hypoxic and hypercapnic ventilatory responses,
      ventilatory recruitment threshold), and baroreflex sensitivity before,
      immediately after, and 3 and 6 h after a 1-h single bout of IH (6-min breathing
      of 13% oxygen mixture 5 times each separated by 6-min recovery). The measurements
      were repeated on a placebo day (at least 1 week apart, in random sequence) when
      subjects were only breathing room air (single-blind protocol). RESULTS: IH
      significantly increased hypercapnic ventilatory responses and reduced ventilatory
      recruitment threshold, and increased oxygen saturation and blood pressures,
      whereas increases in heart rate variability and baroreflex sensitivity were not
      significant. Blood glucose significantly decreased after IH. No such changes were
      observed during the placebo day, except an increase in oxygen saturation. Some of
      the effects lasted 3 h after IH, and some even persisted until 6 h after IH.
      CONCLUSIONS: A single bout of IH induced an initial adaptation to hypoxia, with
      improvement in cardiorespiratory reflexes and reduction in blood glucose.
      Patients with type 2 diabetes could potentially benefit from the application of a
      full (>2 weeks) IH intervention.

PMID- 23536587
TI  - Defense through sensory inactivation: sea hare ink reduces sensory and motor
      responses of spiny lobsters to food odors.
AB  - Antipredator defenses are ubiquitous and diverse. Ink secretion of sea hares
      (Aplysia) is an antipredator defense acting through the chemical senses of
      predators by different mechanisms. The most common mechanism is ink acting as an
      unpalatable repellent. Less common is ink secretion acting as a decoy
      (phagomimic) that misdirects predators' attacks. In this study, we tested another
      possible mechanism--sensory inactivation--in which ink inactivates the predator's
      reception of food odors associated with would-be prey. We tested this hypothesis
      using spiny lobsters, Panulirus argus, as model predators. Ink secretion is
      composed of two glandular products, one being opaline, a viscous substance
      containing concentrations of hundreds of millimolar of total free amino acids.
      Opaline sticks to antennules, mouthparts and other chemosensory appendages of
      lobsters, physically blocking access of food odors to the predator's
      chemosensors, or over-stimulating (short term) and adapting (long term) the
      chemosensors. We tested the sensory inactivation hypotheses by treating the
      antennules with opaline and mimics of its physical and/or chemical properties. We
      compared the effects of these treatments on responses to a food odor for
      chemoreceptor neurons in isolated antennules, as a measure of effect on
      chemosensory input, and for antennular motor responses of intact lobsters, as a
      measure of effect on chemically driven motor behavior. Our results indicate that
      opaline reduces the output of chemosensors by physically blocking reception of
      and response to food odors, and this has an impact on motor responses of
      lobsters. This is the first experimental demonstration of inactivation of
      peripheral sensors as an antipredatory defense.

PMID- 23536586
TI  - Psychometric properties, norms, and factor structure of the diabetes eating
      problem survey-revised in a large sample of children and adolescents with type 1
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to examine the psychometric properties
      of the Diabetes Eating Problem Survey-Revised (DEPS-R) in a large sample of young
      patients with type 1 diabetes, to establish norms, and to validate it against the
      Eating Attitudes Test-12 (EAT-12). RESEARCH DESIGN AND METHODS: A total of 770
      children and adolescents aged 11-19 years with type 1 diabetes completed the DEPS
      R and the EAT-12. In addition, age- and sex-standardized BMI and HbA1c data were
      obtained from the Norwegian Childhood Diabetes Registry. In addition to tests of
      validity, principal axis factoring was conducted to investigate the factor
      structure of the 16-item DEPS-R. RESULTS: The DEPS-R demonstrated satisfactory
      Cronbach alpha (0.89) and was significantly correlated with the EAT-12 (0.65; P <
      0.01), indicating convergent validity. The mean (SD) DEPS-R scores were 11.0
      (10.7) for the total sample and 7.7 (7.4) and 14.2 (2.4) for males and females,
      respectively. CONCLUSIONS: This study replicates and extends previous research
      demonstrating the psychometric properties of the abbreviated 16-item DEPS-R.
      Findings support the utility of this important screening tool to identify
      disturbed eating in young patients with type 1 diabetes.

PMID- 23536588
TI  - Effects of ocean acidification on early life-history stages of the intertidal
      porcelain crab Petrolisthes cinctipes.
AB  - Intertidal zone organisms naturally experience daily fluctuations in pH,
      presently reaching values beyond what is predicted for open ocean surface waters
      from ocean acidification (OA) by the year 2100, and thus present an opportunity
      to study the pH sensitivity of organisms that are presumably adapted to an
      acidified environment. The intertidal zone porcelain crab, Petrolisthes
      cinctipes, was used to study physiological responses to low pH in embryonic,
      larval and newly recruited juvenile life-history stages. In these crabs,
      embryonic development occurs in the pH-variable intertidal zone (pH 6.9-9.5),
      larvae mature in the more stable pelagic environment (pH 7.9-8.2), and juvenile
      crabs settle back into the pH-variable intertidal zone. We examined survival,
      cardiac performance, energetics and morphology in embryonic, larval and juvenile
      crabs exposed to two pH conditions (pH 7.9 and 7.6). Embryos and larvae were
      split by brood between the pH treatments for 9 days to examine brood-specific
      responses to low pH. Hatching success did not differ between pH conditions, but
      ranged from 30% to 95% among broods. Larval survival was not affected by
      acidification, but juvenile survival was reduced by ~30% after longer (40 days)
      exposure to low pH. Embryonic and larval heart rates were 37% and 20% lower at
      low pH, and there was a brood-specific response in embryos. Embryos did not
      increase in volume under acidified conditions, compared with a 15% increase in
      ambient conditions. We conclude that sustained exposure to low pH could be
      detrimental to P. cinctipes embryos and larvae despite the fact that embryos are
      regularly exposed to naturally fluctuating hypercapnic water in the intertidal
      zone. Importantly, our results indicate that early life-history stage responses
      to OA may be brood specific through as yet undetermined mechanisms.

PMID- 23536589
TI  - Impact of ocean acidification on metabolism and energetics during early life
      stages of the intertidal porcelain crab Petrolisthes cinctipes.
AB  - Absorption of elevated atmospheric CO2 is causing surface ocean pH to decline, a
      process known as ocean acidification (OA). To date, few studies have assessed the
      physiological impacts of OA on early life-history stages of intertidal organisms,
      which transition from habitats with fluctuating pH (intertidal zone) to
      relatively stable (pelagic zone) pH environments. We used the intertidal crab
      Petrolisthes cinctipes to determine whether metabolic responses to year 2300
      predictions for OA vary among early developmental stages and to examine whether
      the effects were more pronounced in larval stages developing in the open ocean.
      Oxygen consumption rate, total protein, dry mass, total lipids and C/N were
      determined in late-stage embryos, zoea I larvae and newly settled juveniles
      reared in ambient pH (7.93 +/- 0.06) or low pH (7.58 +/- 0.06). After short-term
      exposure to low pH, embryos displayed 11% and 6% lower metabolism and dry mass,
      respectively, which may have an associated bioenergetic cost of delayed
      development to hatching. However, metabolic responses appeared to vary among
      broods, suggesting significant parental effects among the offspring of six
      females, possibly a consequence of maternal state during egg deposition and
      genetic differences among broods. Larval and juvenile metabolism were not
      affected by acute exposure to elevated CO2. Larvae contained 7% less nitrogen and
      C/N was 6% higher in individuals reared at pH 7.58 for 6 days, representing a
      possible switch from lipid to protein metabolism under low pH; the metabolic
      switch appears to fully cover the energetic cost of responding to elevated CO2.
      Juvenile dry mass was unaffected after 33 days exposure to low pH seawater.
      Increased tolerance to low pH in zoea I larvae and juvenile stages may be a
      consequence of enhanced acid-base regulatory mechanisms, allowing greater
      compensation of extracellular pH changes and thus preventing decreases in
      metabolism after exposure to elevated PCO2. The observed variation in responses
      of P. cinctipes to decreased pH in the present study suggests the potential for
      this species to adapt to future declines in near-shore pH.

PMID- 23536590
TI  - Pairs of pigeons act as behavioural units during route learning and co
      navigational leadership conflicts.
AB  - In many species, group members obtain benefits from moving collectively, such as
      enhanced foraging efficiency or increased predator detection. In situations where
      the group's decision involves integrating individual preferences, group cohesion
      can lead to more accurate outcomes than solitary decisions. In homing pigeons, a
      classic model in avian orientation studies, individuals learn habitual routes
      home, but whether and how co-navigating birds acquire and share route-based
      information is unknown. Using miniature GPS loggers, we examined these questions
      by first training pairs (the smallest possible flocks) of pigeons together, and
      then releasing them with other pairs that had received separate pair-training.
      Our results show that, much like solitary individuals, pairs of birds are able to
      establish idiosyncratic routes that they recapitulate together faithfully. Also,
      when homing with other pairs they exhibit a transition from a compromise- to a
      leadership-like mechanism of conflict resolution as a function of the degree of
      disagreement (distance separating the two preferred routes) between the two
      pairs, although pairs tolerate a greater range of disagreements prior to the
      transition than do single birds. We conclude that through shared experiences
      during past decision-making, pairs of individuals can become units so closely
      coordinated that their behaviour resembles that of single birds. This has
      implications for the behaviour of larger groups, within which certain individuals
      have closer social affiliations or share a history of previous associations.

PMID- 23536591
TI  - Meal consumption is ineffective at maintaining or correcting water balance in a
      desert lizard, Heloderma suspectum.
AB  - Many xeric organisms maintain water balance by relying on dietary and metabolic
      water rather than free water, even when free water may be available. For such
      organisms, hydric state may influence foraging decisions, since meal consumption
      is meeting both energy and water demands. To understand foraging decisions it is
      vital to understand the role of dietary water in maintaining water balance. We
      investigated whether meal consumption was sufficient to maintain water balance in
      captive Gila monsters (Heloderma suspectum) at varying levels of dehydration.
      Gila monsters could not maintain water balance over long time scales through meal
      consumption alone. Animals fed a single meal took no longer to dehydrate than
      controls when both groups were deprived of free water. Additionally, meal
      consumption imparts an acute short-term hydric cost regardless of hydration
      state. Meal consumption typically resulted in a significant elevation in
      osmolality at 6 h post-feeding, and plasma osmolality never fell below pre
      feeding levels despite high water content (~70%) of meals. These results failed
      to support our hypothesis that dietary water is valuable to Gila monsters during
      seasonal drought. When considered in conjunction with previous research, these
      results demonstrate that Gila monsters, unlike many xeric species, are heavily
      reliant on seasonal rainfall and the resulting free-standing water to maintain
      water balance.

PMID- 23536592
TI  - The impact of John Henryism on self-reported health behaviors in African American
      men.
AB  - PURPOSE: African American men have poorer health and higher disease-related
      mortality as compared to non-African American men. John Henryism refers to the
      predisposition to engage in active high-effort coping with environmental
      stressors. Little is known about relationships between John Henryism and personal
      health behaviors in African American men. The study purposes were to examine
      predictive relationships among John Henryism, marital status, age, education
      years, and health insurance on health behaviors in African American men. DESIGN:
      Cross-sectional descriptive study. METHOD: The convenience sample included 60
      African American men (mean age 54.8 + 10.13) recruited from a large urban area in
      the Midwestern United States. FINDINGS: John Henryism significantly predicted
      self-reported health behaviors accounting for 12% of the multiple regression
      model variance. DISCUSSION:  RESULTS: Findings provide early evidence to consider
      in the design of interventions aimed at promoting healthy behaviors in African
      American men.

PMID- 23536593
TI  - Resource assurance predicts specialist and generalist bee activity in drought.
AB  - Many short-lived desert organisms remain in diapause during drought.
      Theoretically, the cues desert species use to continue diapause through drought
      should differ depending on the availability of critical resources, but the
      unpredictability and infrequent occurrence of climate extremes and reduced insect
      activity during such events make empirical tests of this prediction difficult. An
      intensive study of a diverse bee-plant community through a drought event found
      that bee specialists of a drought-sensitive host plant were absent in the drought
      year in contrast to generalist bees and to specialist bees of a drought
      insensitive host plant. Different responses of bee species to drought indicate
      that the diapause cues used by bee species allow them to reliably predict host
      availability. Species composition of the bee community in drought shifted towards
      mostly generalist species. However, we predict that more frequent and extended
      drought, predicted by climate change models for southwest North America, will
      result in bee communities that are species-poor and dominated by specialist
      species, as found today in the most arid desert region of North America.

PMID- 23536594
TI  - A new Early Cretaceous eutherian mammal from the Sasayama Group, Hyogo, Japan.
AB  - We here describe a new Early Cretaceous (early Albian) eutherian mammal,
      Sasayamamylos kawaii gen. et sp. nov., from the 'Lower Formation' of the Sasayama
      Group, Hyogo Prefecture, Japan. Sasayamamylos kawaii is characterized by a robust
      dentary, a distinct angle on the ventral margin of the dentary at the posterior
      end of the mandibular symphysis, a lower dental formula of 3-4 : 1 : 4 : 3, a
      robust lower canine, a non-molariform lower ultimate premolar, and a secondarily
      reduced entoconid on the molars. To date, S. kawaii is the earliest known
      eutherian mammal possessing only four premolars, which demonstrates that the
      reduction in the premolar count in eutherians started in the late Early
      Cretaceous. The occurrence of S. kawaii implies that the relatively rapid
      diversification of eutherians in the mid-Cretaceous had already started by the
      early Albian.

PMID- 23536595
TI  - Temperature and CO(2) additively regulate physiology, morphology and genomic
      responses of larval sea urchins, Strongylocentrotus purpuratus.
AB  - Ocean warming and ocean acidification, both consequences of anthropogenic
      production of CO2, will combine to influence the physiological performance of
      many species in the marine environment. In this study, we used an integrative
      approach to forecast the impact of future ocean conditions on larval purple sea
      urchins (Strongylocentrotus purpuratus) from the northeast Pacific Ocean. In
      laboratory experiments that simulated ocean warming and ocean acidification, we
      examined larval development, skeletal growth, metabolism and patterns of gene
      expression using an orthogonal comparison of two temperature (13 degrees C and 18
      degrees C) and pCO2 (400 and 1100 MUatm) conditions. Simultaneous exposure to
      increased temperature and pCO2 significantly reduced larval metabolism and
      triggered a widespread downregulation of histone encoding genes. pCO2 but not
      temperature impaired skeletal growth and reduced the expression of a major
      spicule matrix protein, suggesting that skeletal growth will not be further
      inhibited by ocean warming. Importantly, shifts in skeletal growth were not
      associated with developmental delay. Collectively, our results indicate that
      global change variables will have additive effects that exceed thresholds for
      optimized physiological performance in this keystone marine species.

PMID- 23536597
TI  - Inferred L/M cone opsin polymorphism of ancestral tarsiers sheds dim light on the
      origin of anthropoid primates.
AB  - Tarsiers are small nocturnal primates with a long history of fuelling debate on
      the origin and evolution of anthropoid primates. Recently, the discovery of M and
      L opsin genes in two sister species, Tarsius bancanus (Bornean tarsier) and
      Tarsius syrichta (Philippine tarsier), respectively, was interpreted as evidence
      of an ancestral long-to-middle (L/M) opsin polymorphism, which, in turn,
      suggested a diurnal or cathemeral (arrhythmic) activity pattern. This view is
      compatible with the hypothesis that stem tarsiers were diurnal; however, a
      reversion to nocturnality during the Middle Eocene, as evidenced by hyper
      enlarged orbits, predates the divergence of T. bancanus and T. syrichta in the
      Late Miocene. Taken together, these findings suggest that some nocturnal tarsiers
      possessed high-acuity trichromatic vision, a concept that challenges prevailing
      views on the adaptive origins of the anthropoid visual system. It is, therefore,
      important to explore the plausibility and antiquity of trichromatic vision in the
      genus Tarsius. Here, we show that Sulawesi tarsiers (Tarsius tarsier), a
      phylogenetic out-group of Philippine and Bornean tarsiers, have an L opsin gene
      that is more similar to the L opsin gene of T. syrichta than to the M opsin gene
      of T. bancanus in non-synonymous nucleotide sequence. This result suggests that
      an L/M opsin polymorphism is the ancestral character state of crown tarsiers and
      raises the possibility that many hallmarks of the anthropoid visual system
      evolved under dim (mesopic) light conditions. This interpretation challenges the
      persistent nocturnal-diurnal dichotomy that has long informed debate on the
      origin of anthropoid primates.

PMID- 23536596
TI  - Large-scale phylogeny of chameleons suggests African origins and Eocene
      diversification.
AB  - Oceanic dispersal has emerged as an important factor contributing to
      biogeographic patterns in numerous taxa. Chameleons are a clear example of this,
      as they are primarily found in Africa and Madagascar, but the age of the family
      is post-Gondwanan break-up. A Malagasy origin for the family has been suggested,
      yet this hypothesis has not been tested using modern biogeographic methods with a
      dated phylogeny. To examine competing hypotheses of African and Malagasy origins,
      we generated a dated phylogeny using between six and 13 genetic markers, for up
      to 174 taxa representing greater than 90 per cent of all named species. Using
      three different ancestral-state reconstruction methods (Bayesian and likelihood
      approaches), we show that the family most probably originated in Africa, with two
      separate oceanic dispersals to Madagascar during the Palaeocene and the
      Oligocene, when prevailing oceanic currents would have favoured eastward
      dispersal. Diversification of genus-level clades took place in the Eocene, and
      species-level diversification occurred primarily in the Oligocene. Plio
      Pleistocene speciation is rare, resulting in a phylogeny dominated by palaeo
      endemic species. We suggest that contraction and fragmentation of the Pan-African
      forest coupled to an increase in open habitats (savannah, grassland, heathland),
      since the Oligocene played a key role in diversification of this group through
      vicariance.

PMID- 23536598
TI  - Fungal symbioses in hornworts: a chequered history.
AB  - Hornworts are considered the sister group to vascular plants, but their fungal
      associations remain largely unexplored. The ancestral symbiotic condition for all
      plants is, nonetheless, widely assumed to be arbuscular mycorrhizal with
      Glomeromycota fungi. Owing to a recent report of other fungi in some non-vascular
      plants, here we investigate the fungi associated with diverse hornworts
      worldwide, using electron microscopy and molecular phylogenetics. We found that
      both Glomeromycota and Mucoromycotina fungi can form symbioses with most
      hornworts, often simultaneously. This discovery indicates that ancient
      terrestrial plants relied on a wider and more versatile symbiotic repertoire than
      previously thought, and it highlights the so far unappreciated ecological and
      evolutionary role of Mucoromycotina fungi.

PMID- 23536599
TI  - Individual heterogeneity and costly punishment: a volunteer's dilemma.
AB  - Social control and the enforcement of social norms glue a society together. It
      has been shown theoretically and empirically that informal punishment of
      wrongdoers fosters cooperation in human groups. Most of this research has focused
      on voluntary and uncoordinated punishment carried out by individual group
      members. However, as punishment is costly, it is an open question as to why
      humans engage in the punishment of wrongdoers even in one-time-only encounters.
      While evolved punitive preferences have been advocated as proximate explanations
      for such behaviour, the strategic nature of the punishment situation has remained
      underexplored. It has been suggested to conceive of the punishment situation as a
      volunteer's dilemma (VOD), where only one individual's action is necessary and
      sufficient to punish the wrongdoer. Here, we show experimentally that
      implementing the punishment situation as a VOD sustains cooperation in an
      environment where punishers and non-punishers coexist. Moreover, we show that
      punishment-cost heterogeneity allows individuals to tacitly agree on only the
      strongest group member carrying out the punishment, thereby increasing the
      effectiveness and efficiency of social norm enforcement. Our results corroborate
      that costly peer punishment can be explained without assuming punitive
      preferences and show that centralized sanctioning institutions can emerge from
      arbitrary individual differences.

PMID- 23536601
TI  - Antlers on the Arctic Refuge: capturing multi-generational patterns of calving
      ground use from bones on the landscape.
AB  - Bone accumulations faithfully record historical ecological data on animal
      communities, and owing to millennial-scale bone survival on high-latitude
      landscapes, have exceptional potential for extending records on arctic
      ecosystems. For the Porcupine Caribou Herd, maintaining access to calving grounds
      on the Arctic National Wildlife Refuge (ANWR, Alaska) is a central management
      concern. However, variability in calving ground geography over the 30+ years of
      monitoring suggests establishing the impacts of climate change and potential
      petroleum development on future calving success could benefit from extended
      temporal perspectives. Using accumulations of female antlers (shed within days of
      calving) and neonatal skeletons, we test if caribou calving grounds develop
      measureable and characteristic bone accumulations and if skeletal data may be
      helpful in establishing a fuller, historically integrated understanding of
      landscape and habitat needs. Bone surveys of an important ANWR calving area
      reveal abundant shed antlers (reaching 10(3) km(-2)) and high proportional
      abundance of newborn skeletal individuals (up to 60% neonate). Openly vegetated
      riparian terraces, which compose less than 10 per cent of ANWR calving grounds,
      yield significantly higher antler concentrations than more abundant habitats
      traditionally viewed as primary calving terrain. Differences between habitats
      appear robust to potential differences in bone visibility. The distribution of
      antler weathering stages mirrors known multi-decadal calving histories and
      highlights portions of the antler accumulation that probably significantly
      extends records of calving activity. Death assemblages offer historically
      integrated ecological data valuable for the management and conservation of faunas
      across polar latitudes.

PMID- 23536600
TI  - Brain reorganization, not relative brain size, primarily characterizes anthropoid
      brain evolution.
AB  - Comparative analyses of primate brain evolution have highlighted changes in size
      and internal organization as key factors underlying species diversity. It
      remains, however, unclear (i) how much variation in mosaic brain reorganization
      versus variation in relative brain size contributes to explaining the structural
      neural diversity observed across species, (ii) which mosaic changes contribute
      most to explaining diversity, and (iii) what the temporal origin, rates and
      processes are that underlie evolutionary shifts in mosaic reorganization for
      individual branches of the primate tree of life. We address these questions by
      combining novel comparative methods that allow assessing the temporal origin,
      rate and process of evolutionary changes on individual branches of the tree of
      life, with newly available data on volumes of key brain structures (prefrontal
      cortex, frontal motor areas and cerebrocerebellum) for a sample of 17 species
      (including humans). We identify patterns of mosaic change in brain evolution that
      mirror brain systems previously identified by electrophysiological and anatomical
      tract-tracing studies in non-human primates and functional connectivity MRI
      studies in humans. Across more than 40 Myr of anthropoid primate evolution,
      mosaic changes contribute more to explaining neural diversity than changes in
      relative brain size, and different mosaic patterns are differentially selected
      for when brains increase or decrease in size. We identify lineage-specific
      evolutionary specializations for all branches of the tree of life covered by our
      sample and demonstrate deep evolutionary roots for mosaic patterns associated
      with motor control and learning.

PMID- 23536602
TI  - Early play may predict later dominance relationships in yellow-bellied marmots
      (Marmota flaviventris).
AB  - Play has been defined as apparently functionless behaviour, yet since play is
      costly, models of adaptive evolution predict that it should have some beneficial
      function (or functions) that outweigh its costs. We provide strong evidence for a
      long-standing, but poorly supported hypothesis: that early social play is
      practice for later dominance relationships. We calculated the relative dominance
      rank by observing the directional outcome of playful interactions in juvenile and
      yearling yellow-bellied marmots (Marmota flaviventris) and found that these rank
      relationships were correlated with later dominance ranks calculated from
      agonistic interactions, however, the strength of this relationship attenuated
      over time. While play may have multiple functions, one of them may be to
      establish later dominance relationships in a minimally costly way.

PMID- 23536604
TI  - Wing flexibility enhances load-lifting capacity in bumblebees.
AB  - The effect of wing flexibility on aerodynamic force production has emerged as a
      central question in insect flight research. However, physical and computational
      models have yielded conflicting results regarding whether wing deformations
      enhance or diminish flight forces. By experimentally stiffening the wings of live
      bumblebees, we demonstrate that wing flexibility affects aerodynamic force
      production in a natural behavioural context. Bumblebee wings were artificially
      stiffened in vivo by applying a micro-splint to a single flexible vein joint, and
      the bees were subjected to load-lifting tests. Bees with stiffened wings showed
      an 8.6 per cent reduction in maximum vertical aerodynamic force production, which
      cannot be accounted for by changes in gross wing kinematics, as stroke amplitude
      and flapping frequency were unchanged. Our results reveal that flexible wing
      design and the resulting passive deformations enhance vertical force production
      and load-lifting capacity in bumblebees, locomotory traits with important
      ecological implications.

PMID- 23536603
TI  - Reception and learning of electric fields in bees.
AB  - Honeybees, like other insects, accumulate electric charge in flight, and when
      their body parts are moved or rubbed together. We report that bees emit constant
      and modulated electric fields when flying, landing, walking and during the waggle
      dance. The electric fields emitted by dancing bees consist of low- and high
      frequency components. Both components induce passive antennal movements in
      stationary bees according to Coulomb's law. Bees learn both the constant and the
      modulated electric field components in the context of appetitive proboscis
      extension response conditioning. Using this paradigm, we identify
      mechanoreceptors in both joints of the antennae as sensors. Other
      mechanoreceptors on the bee body are potentially involved but are less sensitive.
      Using laser vibrometry, we show that the electrically charged flagellum is moved
      by constant and modulated electric fields and more strongly so if sound and
      electric fields interact. Recordings from axons of the Johnston organ document
      its sensitivity to electric field stimuli. Our analyses identify electric fields
      emanating from the surface charge of bees as stimuli for mechanoreceptors, and as
      biologically relevant stimuli, which may play a role in social communication.

PMID- 23536605
TI  - Tyrosine 284 phosphorylation is required for ClC-3 chloride channel activation in
      vascular smooth muscle cells.
AB  - AIMS: The ClC-3 chloride channel (and current, ICl,ClC-3) plays an important role
      in cell volume regulation, proliferation, and apoptosis in vascular smooth muscle
      cells, and is a potential target for prevention of vascular remodelling and
      stroke. However, modulation of ICl,ClC-3 by intercellular signalling is not fully
      understood. Although it has been suggested that tyrosine phosphorylation is
      required for ICl,ClC-3 activation, the potential tyrosine residues in the ClC-3
      protein are not clear. In the present study, the critical tyrosine residues in
      ClC-3 protein were investigated. METHODS AND RESULTS: Site-specific mutagenesis,
      immunoprecipitation, patch clamp, and Cl(-) transport imaging techniques were
      employed. We found that activation of ICl,ClC-3 was associated with tyrosine
      phosphorylation of the ClC-3 protein. Three potential tyrosine residues, Y284,
      Y572, and Y631, were mutated to phenylalanine, and only mutation, at Y284 within
      a consensus Src-phosphorylation site, completely blocked ICl,ClC-3.
      Phosphomimetic mutation Y284D increased the Cl(-) current and Cl(-) efflux
      mediated by ClC-3. The Y284F mutation completely abolished the protective effect
      of ClC-3 on apoptosis, whereas the Y284D mutation potentiated it. There was an
      interaction between Src kinase and ClC-3 protein, and the Y284D mutation
      abrogated the inhibitory effect of SU6656, a Src family kinase inhibitor, on ClC
      3 Cl(-) current. CONCLUSION: Tyrosine 284 phosphorylation in the ClC-3 channel
      targeted by Src kinase is an important molecular mechanism for ClC-3 channel
      activation.

PMID- 23536607
TI  - Triple mode of action of flecainide in catecholaminergic polymorphic ventricular
      tachycardia: reply.

PMID- 23536606
TI  - Localized RhoA GTPase activity regulates dynamics of endothelial monolayer
      integrity.
AB  - AIMS: Endothelial cells (ECs) control vascular permeability by forming a
      monolayer that is sealed by extracellular junctions. Various mediators modulate
      the endothelial barrier by acting on junctional protein complexes and the
      therewith connected F-actin cytoskeleton. Different Rho GTPases participate in
      this modulation, but their mechanisms are still partly resolved. Here, we aimed
      to elucidate whether the opening and closure of the endothelial barrier are
      associated with distinct localized RhoA activities at the subcellular level.
      METHODS AND RESULTS: Live fluorescence resonance energy transfer (FRET)
      microscopy revealed spatially distinct RhoA activities associated with different
      aspects of the regulation of endothelial monolayer integrity. Unstimulated ECs
      were characterized by hotspots of RhoA activity at their periphery. Thrombin
      receptor activation in the femoral vein of male wistar rats and in cultured ECs
      enhanced RhoA activity at membrane protrusions, followed by a more sustained RhoA
      activity associated with cytoplasmic F-actin filaments, where prolonged RhoA
      activity coincided with cellular contractility. Unexpectedly, thrombin-induced
      peripheral RhoA hotspots were not spatially correlated to the formation of large
      inter-endothelial gaps. Rather, spontaneous RhoA activity at membrane protrusions
      coincided with the closure of inter-endothelial gaps. Electrical impedance
      measurements showed that RhoA signalling is essential for this protrusive
      activity and maintenance of barrier restoration. CONCLUSION: Spontaneous RhoA
      activity at membrane protrusions is spatially associated with closure, but not
      formation of inter-endothelial gaps, whereas RhoA activity at distant contractile
      filaments contributes to thrombin-induced disruption of junctional integrity.
      Thus, these data indicate that distinct RhoA activities are associated with
      disruption and re-annealing of endothelial junctions.

PMID- 23536608
TI  - Novel insights into the composition, variation, organization, and expression of
      the low-molecular-weight glutenin subunit gene family in common wheat.
AB  - Low-molecular-weight glutenin subunits (LMW-GS), encoded by a complex multigene
      family, play an important role in the processing quality of wheat flour. Although
      members of this gene family have been identified in several wheat varieties, the
      allelic variation and composition of LMW-GS genes in common wheat are not well
      understood. In the present study, using the LMW-GS gene molecular marker system
      and the full-length gene cloning method, a comprehensive molecular analysis of
      LMW-GS genes was conducted in a representative population, the micro-core
      collections (MCC) of Chinese wheat germplasm. Generally, >15 LMW-GS genes were
      identified from individual MCC accessions, of which 4-6 were located at the Glu
      A3 locus, 3-5 at the Glu-B3 locus, and eight at the Glu-D3 locus. LMW-GS genes at
      the Glu-A3 locus showed the highest allelic diversity, followed by the Glu-B3
      genes, while the Glu-D3 genes were extremely conserved among MCC accessions.
      Expression and sequence analysis showed that 9-13 active LMW-GS genes were
      present in each accession. Sequence identity analysis showed that all i-type
      genes present at the Glu-A3 locus formed a single group, the s-type genes located
      at Glu-B3 and Glu-D3 loci comprised a unique group, while high-diversity m-type
      genes were classified into four groups and detected in all Glu-3 loci. These
      results contribute to the functional analysis of LMW-GS genes and facilitate
      improvement of bread-making quality by wheat molecular breeding programmes.

PMID- 23536609
TI  - Plant WEE1 kinase is cell cycle regulated and removed at mitosis via the 26S
      proteasome machinery.
AB  - In yeasts and animals, premature entry into mitosis is prevented by the
      inhibitory phosphorylation of cyclin-dependent kinase (CDK) by WEE1 kinase, and,
      at mitosis, WEE1 protein is removed through the action of the 26S proteasome.
      Although in higher plants WEE1 function has been confirmed in the DNA replication
      checkpoint, Arabidopsis wee1 insertion mutants grow normally, and a role for the
      protein in the G2/M transition during an unperturbed plant cell cycle is yet to
      be confirmed. Here data are presented showing that the inhibitory effect of WEE1
      on CDK activity in tobacco BY-2 cell cultures is cell cycle regulated
      independently of the DNA replication checkpoint: it is high during S-phase but
      drops as cells traverse G2 and enter mitosis. To investigate this mechanism
      further, a yeast two-hybrid screen was undertaken to identify proteins
      interacting with Arabidopsis WEE1. Three F-box proteins and a subunit of the
      proteasome complex were identified, and bimolecular fluorescence complementation
      confirmed an interaction between AtWEE1 and the F-box protein SKP1 interacting
      partner 1 (SKIP1). Furthermore, the AtWEE1-green fluorescent protein (GFP) signal
      in Arabidopsis primary roots treated with the proteasome inhibitor MG132 was
      significantly increased compared with mock-treated controls. Expression of AtWEE1
      YFP(C) (C-terminal portion of yellow fluorescent protein) or AtWEE1 per se in
      tobacco BY-2 cells resulted in a premature increase in the mitotic index compared
      with controls, whereas co-expression of AtSKIP1-YFP(N) negated this effect. These
      data support a role for WEE1 in a normal plant cell cycle and its removal at
      mitosis via the 26S proteasome.

PMID- 23536610
TI  - Myocardial reperfusion injury: looking beyond primary PCI.
AB  - Coronary heart disease (CHD) is the leading cause of death and disability in
      Europe. For patients presenting with an acute ST-segment elevation myocardial
      infarction (STEMI), timely myocardial reperfusion using either thrombolytic
      therapy or primary percutaneous coronary intervention (PPCI) is the most
      effective therapy for limiting myocardial infarct (MI) size, preserving left
      ventricular systolic function and reducing the onset of heart failure. Despite
      this, the morbidity and mortality of STEMI patients remain significant, and novel
      therapeutic interventions are required to improve clinical outcomes in this
      patient group. Paradoxically, the process of myocardial reperfusion can itself
      induce cardiomyocyte death-a phenomenon which has been termed 'myocardial
      reperfusion injury' (RI), the irreversible consequences of which include
      microvascular obstruction and myocardial infarction. Unfortunately, there is
      currently no effective therapy for preventing myocardial RI in STEMI patients
      making it an important residual target for cardioprotection. Previous attempts to
      translate cardioprotective therapies (antioxidants, calcium-channel blockers, and
      anti-inflammatory agents) for reducing RI into the clinic, have been
      unsuccessful. An improved understanding of the pathophysiological mechanisms
      underlying RI has resulted in the identification of several promising mechanical
      (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic
      hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide,
      cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial
      RI, many of which have shown promise in initial proof-of-principle clinical
      studies. In this article, we review the pathophysiology underlying myocardial RI,
      and highlight the potential therapeutic interventions which may be used in the
      future to prevent RI and improve clinical outcomes in patients with CHD.

PMID- 23536612
TI  - Probability of detecting Porcine reproductive and respiratory syndrome virus
      infection using pen-based swine oral fluid specimens as a function of within-pen
      prevalence.
AB  - Pen-based oral fluid sampling has proven to be an efficient method for
      surveillance of infectious diseases in swine populations. To better interpret
      diagnostic results, the performance of oral fluid assays (antibody- and nucleic
      acid-based) must be established for pen-based oral fluid samples. Therefore, the
      objective of the current study was to determine the probability of detecting
      Porcine reproductive and respiratory syndrome virus (PRRSV) infection in pen
      based oral fluid samples from pens of known PRRSV prevalence. In 1 commercial
      swine barn, 25 pens were assigned to 1 of 5 levels of PRRSV prevalence (0%, 4%,
      12%, 20%, or 36%) by placing a fixed number (0, 1, 3, 5, or 9) of PRRSV-positive
      pigs (14 days post PRRSV modified live virus vaccination) in each pen. Prior to
      placement of the vaccinated pigs, 1 oral fluid sample was collected from each
      pen. Thereafter, 5 oral fluid samples were collected from each pen, for a total
      of 150 samples. To confirm individual pig PRRSV status, serum samples from the
      PRRSV-negative pigs (n = 535) and the PRRSV vaccinated pigs (n = 90) were tested
      for PRRSV antibodies and PRRSV RNA. The 150 pen-based oral fluid samples were
      assayed for PRRSV antibody and PRRSV RNA at 6 laboratories. Among the 100 samples
      from pens containing >=1 positive pig (>=4% prevalence) and tested at the 6
      laboratories, the mean positivity was 62% for PRRSV RNA and 61% for PRRSV
      antibody. These results support the use of pen-based oral fluid sampling for
      PRRSV surveillance in commercial pig populations.

PMID- 23536613
TI  - Sensitivity and specificity of histology for diagnoses of four common pathogens
      and detection of nontarget pathogens in adult Chinook salmon (Oncorhynchus
      tshawytscha) in fresh water.
AB  - Histology is often underutilized in aquatic animal disease screening and
      diagnostics. The agreement between histological classifications of infection and
      results using diagnostic testing from the American Fisheries Society's Blue Book
      was conducted with 4 common salmon pathogens: Aeromonas salmonicida,
      Renibacterium salmoninarum, Ceratomyxa shasta, and Nanophyetus salmincola. Adult
      Chinook salmon (Oncorhynchus tshawytscha) in Oregon were evaluated, and agreement
      between tests was calculated. Live and dead (both pre- and postspawning) salmon
      were collected from the Willamette River, Oregon, its tributaries, the Willamette
      Hatchery, and after holding in cool, pathogen-free water during maturation at
      Oregon State University. Sensitivity and specificity of histology compared to
      Blue Book methods for all fish, live fish only, and dead (pre- and postspawned
      combined) fish only were, respectively, as follows: A. salmonicida (n = 105):
      specificity 87.5%, 87.5%, 87.5% and sensitivity 38.6%, 14.8%, 60.0%; R.
      salmoninarum (n = 111): specificity 91.9%, 85.7%, 97.7% and sensitivity 16.0%,
      7.1%, 27.2%; C. shasta (n = 136): specificity 56.0%, 63.3%, 28.6% and sensitivity
      83.3%, 86.2%, 71.4%; N. salmincola (n = 228): specificity 68.2%, 66.7%, not
      possible to calculate for dead fish and sensitivity 83.5%, 80.5%, 87.3%. The
      specificity was good for bacterial pathogens. This was not the case for C.
      shasta, likely due to detection of presporogenic forms only by histology.
      Sensitivity of histology for bacterial pathogens was low with the exception of
      dead fish with A. salmonicida. Kappa analysis for agreement between Blue Book and
      histology methods was poor to moderate. However, histological observations
      revealed the presence of other pathogens that would not be detected by other
      methods.

PMID- 23536611
TI  - Effect of ivabradine in patients with left-ventricular systolic dysfunction: a
      pooled analysis of individual patient data from the BEAUTIFUL and SHIFT trials.
AB  - AIMS: To test the effect of ivabradine on the outcomes in a broad population with
      left-ventricular (LV) systolic dysfunction with coronary artery disease (CAD)
      and/or heart failure (HF). METHODS AND RESULTS: Individual trial data from
      BEAUTIFUL and SHIFT were pooled to evaluate the effect of ivabradine on the
      outcomes in patients with LV dysfunction and heart rate >= 70 b.p.m. The pooled
      population (n = 11 897; baseline age 62.3 +/- 10.4 years, heart rate 79.6 +/- 9.2
      b.p.m., and LV ejection fraction 30.3 +/- 5.6%) was well treated according to
      current recommendations (87% beta-blockers, 90% renin-angiotensin system
      inhibitors). Median follow-up was 21 months. Treatment with ivabradine was
      associated with a 13% relative risk reduction for the composite of cardiovascular
      mortality or HF hospitalization (P < 0.001 vs. placebo); this was driven by HF
      hospitalizations (19%, P < 0.001). There were also significant relative risk
      reductions for the composite of cardiovascular mortality, HF hospitalizations, or
      myocardial infarction (MI) hospitalization (15%, P < 0.001); cardiovascular
      mortality and non-fatal MI (10%, P = 0.023); and MI hospitalization (23%, P =
      0.009). Similar results were found in patients with differing clinical profiles.
      Ivabradine was well tolerated. CONCLUSION: Ivabradine may be important for the
      improvement of clinical outcomes in patients with LV systolic dysfunction and
      heart rate >= 70 b.p.m., whatever the primary clinical presentation (CAD or HF)
      or clinical status (NYHA class).

PMID- 23536614
TI  - Diagnostic performance of fecal quantitative real-time polymerase chain reaction
      for detection of Lawsonia intracellularis-associated proliferative enteropathy in
      nursery pigs.
AB  - Quantitative polymerase chain reaction (qPCR) tests for detection and
      quantification of Lawsonia intracellularis in feces from pigs have been
      developed. The objective of the current study was to evaluate the diagnostic
      performance of a fecal qPCR test for detection of nursery pigs with L.
      intracellularis-associated proliferative enteropathy (PE) under field conditions.
      Furthermore, the diagnostic performance for different subpopulations of pigs was
      investigated, including pigs infected or noninfected with Porcine circovirus-2,
      Brachyspira pilosicoli, and Escherichia coli. The diagnostic performance was
      evaluated in terms of diagnostic sensitivity and specificity. Data from pigs
      originating from 20 herds with antibiotic treatment requiring diarrhea outbreaks
      from a prior study were reused. Before treatment, pigs were randomly selected for
      histological and immunohistochemical examination of intestinal segments and fecal
      quantification of L. intracellularis by qPCR. A total of 313 pigs (157 without
      diarrhea, 156 with diarrhea) were included in the statistical analysis, and 37
      pigs (11.8%) were classified as PE positives (defined as proliferative
      histological lesions in combination with L. intracellularis demonstration by
      immunohistochemistry). Lawsonia intracellularis was detected by qPCR in feces
      from 91 pigs (29.1%). A nonparametric receiver operating characteristic (ROC)
      analysis provided an area under the ROC curve (0.93) and an optimal cutoff value
      of 4.8 log10 L. intracellularis bacteria/g feces. This cutoff provided a
      diagnostic sensitivity of 0.84 and diagnostic specificity of 0.93. The diagnostic
      sensitivity and specificity were significantly different between herds (P <
      0.0001). Numerically, diagnostic sensitivity and specificity were different
      between subpopulations of pigs, but no significant differences were demonstrated.

PMID- 23536615
TI  - Evaluation of virus isolation, one-step real-time reverse transcription
      polymerase chain reaction assay, and two rapid influenza diagnostic tests for
      detecting canine Influenza A virus H3N8 shedding in dogs.
AB  - Sustained transmission of canine Influenza A virus (CIV) H3N8 among U.S. dogs
      underscores the threat influenza continues to pose to canine health. Because
      rapid and accurate detection of infection is critical to the diagnosis and
      control of CIV, the 2 main objectives of the current study were to estimate and
      compare the sensitivities of CIV testing methods on canine swab samples and to
      evaluate the performance of Flu DetectTM (Synbiotics Corp., Kansas City, MO) for
      detecting CIV nasal shedding in high-risk shelter dogs. To address the first
      objective, nasal and pharyngeal swab samples were collected from 124 shelter and
      household dogs seen by Colorado State University Veterinary Teaching Hospital
      clinicians for canine infectious respiratory disease between April 2006 and March
      2007 and tested for CIV shedding using virus isolation, the rapid influenza
      diagnostic test Directigen Flu A+BTM (BD Diagnostic Systems, Sparks, MD), and
      real-time reverse transcription polymerase chain reaction (RT-PCR). For the
      second objective, 1,372 dogs with unknown respiratory health status were sampled
      from 6 U.S. shelters from December 2009 to November 2010. Samples were tested for
      presence of CIV using real-time RT-PCR and Flu Detect. Using a stochastic latent
      class modeling approach, the median sensitivities of virus isolation, rapid
      influenza diagnostic test, and real-time RT-PCR were 72%, 65%, and 95%,
      respectively. The Flu Detect test performed poorly for detecting CIV nasal
      shedding compared to real-time RT-PCR. In conclusion, the real-time RT-PCR has
      the highest sensitivity for detecting virus nasal shedding and can be used as a
      rapid diagnostic test for CIV.

PMID- 23536616
TI  - The new EuroSCORE II does not improve prediction of mortality in high-risk
      patients undergoing cardiac surgery: a collaborative analysis of two European
      centres.
AB  - OBJECTIVES: Prediction of operative risk in adult patients undergoing cardiac
      surgery remains a challenge, particularly in high-risk patients. In Europe, the
      EuroSCORE is the most commonly used risk-prediction model, but is no longer
      accurately calibrated to be used in contemporary practice. The new EuroSCORE II
      was recently published in an attempt to improve risk prediction. We sought to
      assess the predictive value of EuroSCORE II compared with the original EuroSCOREs
      in high-risk patients. METHODS: Patients who underwent surgery between 1 April
      2006 and 31 March 2011 with a preoperative logistic EuroSCORE >= 10 were
      identified from prospective cardiac surgical databases at two European
      institutions. Additional variables included in EuroSCORE II, but not in the
      original EuroSCORE, were retrospectively collected through patient chart review.
      The C-statistic to predict in-hospital mortality was calculated for the additive
      EuroSCORE, logistic EuroSCORE and EuroSCORE II models. The Hosmer-Lemeshow test
      was used to assess model calibration by comparing observed and expected mortality
      in a number of risk strata. The fit of EuroSCORE II was compared with the
      original EuroSCOREs using Akaike's Information Criterion (AIC). RESULTS: A total
      of 933 patients were identified; the median additive EuroSCORE was 10
      (interquartile range [IQR] 9-11), median logistic EuroSCORE 15.3 (IQR 12.0-24.1)
      and median EuroSCORE II 9.3 (5.8-15.6). There were 90 (9.7%) in-hospital deaths.
      None of the EuroSCORE models performed well with a C-statistic of 0.67 for the
      additive EuroSCORE and EuroSCORE II, and 0.66 for the logistic EuroSCORE. Model
      calibration was poor for the EuroSCORE II (chi-square 16.5; P = 0.035). Both the
      additive EuroSCORE and logistic EuroSCORE had a numerically better model fit, the
      additive EuroSCORE statistically significantly so (difference in AIC was -5.66; P
      = 0.017). CONCLUSIONS: The new EuroSCORE II does not improve risk prediction in
      high-risk patients undergoing adult cardiac surgery when compared with original
      additive and logistic EuroSCOREs. The key problem of risk stratification in high
      risk patients has not been addressed by this new model. Future iterations of the
      score should explore more advanced statistical methods and focus on developing
      procedure-specific algorithms. Moreover, models that predict complications in
      addition to mortality may prove to be of increasing value.

PMID- 23536617
TI  - Periprosthetic regurgitation after aortic valve intervention and stroke.

PMID- 23536618
TI  - Depression, obesity, and smoking were independently associated with inadequate
      glycemic control in patients with type 1 diabetes.
AB  - OBJECTIVE: The aim of this study was to explore the associations between
      inadequate glycemic control of diabetes and psychological, anthropometric, and
      lifestyle variables in a population-based cohort of type 1 diabetes patients.
      DESIGN: Cross-sectional study. METHODS: In this study, 292 patients with type 1
      diabetes, aged 1859 years, participated. psychological data were assessed by self
      report instruments: Hospital Anxiety and Depression Scale and Toronto Alexithymia
      Scale-20. Anthropometrics, blood analyses, data from medical records, and data
      from the Swedish National Diabetes Registry were collected. RESULTS: Self
      reported depression (adjusted odds ratio (AOR) 4.8), obesity (AOR 4.3), and
      smoking (AOR 3.0) were independently associated with inadequate glycemic control
      of diabetes (HbA1c>8.6%). Gender-stratified analyses showed that self-reported
      depression (AOR 19.8) and obesity (AOR 7.0) in women and smoking in men (AOR 4.2)
      were associated with HbA1c>8.6%. Alexithymia, antidepressant medication, and
      physical inactivity were associated with HbA1c>8.6% only in bivariate analyses.
      Alexithymia, self-rated anxiety, physical inactivity, and absence of abdominal
      obesity were associated with self-reported depression. CONCLUSIONS: Depression
      was the only psychological factor independently associated with HbA1c>8.6%. The
      association was of comparable importance as obesity and smoking, well-known risk
      factors for inadequate glycemic control and diabetes complications. The
      association between depression and HbA1c>8.6% was particularly strong for women.
      Alexithymia, which is a relatively stable personality trait, was associated with
      depression. In the future care of patients with diabetes, psychological aspects
      should be considered alongside anthropometrics and lifestyle factors in order to
      achieve the goals for HbA1c.

PMID- 23536619
TI  - To evaluate the effect of combining photo-activation therapy with platelet-rich
      plasma injections for the novel treatment of osteoarthritis.
AB  - OBJECTIVE: To evaluate the effect of combining photo-activation therapy with
      platelet-rich plasma injections for the novel treatment of osteoarthritis.
      DESIGN: We present a case report of osteoarthritis of the knee treated with photo
      activated platelet-rich plasma injections (PAPRP). METHODS: After utilising
      conventional osteoarthritis treatment methods a patient underwent a course of
      PAPRP injections. The patient outcome was measured using the numerical pain
      rating scale (NPRS) and the Western Ontario and McMaster Universities Arthritis
      (WOMAC) Index. RESULTS: Following treatment the patient reported improvements in
      both pain and function as measured by the NPRS and WOMAC Index, respectively. The
      patient was followed up for 18 weeks, at which time no significant complications
      were noted. CONCLUSIONS: In this case report of osteoarthritis, with strict
      control of conventional therapy variables, PAPRP injections demonstrated
      improvement in all recorded outcome measures. The results of this case report
      highlight the need to further investigate the use of PAPRP in the treatment of
      symptomatic knee osteoarthritis.

PMID- 23536620
TI  - Familial aggregation of maxillary lateral incisor agenesis (MLIA).
AB  - Agenesis of maxillary lateral incisors and mandibular second premolars is the
      most frequent form of hypodontia. Its prevalence varies across population from
      0.8% to 4.5%. Genetic aberrations and environmental factors may cause agenesis of
      one or more teeth. The management of child having such a problem is very
      important since diastema in teeth especially in upper anteriors not only affects
      child's physical appearance but also its psychological development as the child
      wants to look like other children. In this article is presented a case of non
      syndromic agenesis of maxillary lateral incisors (MLIA) and mandibular central
      incisors in a 10-year-old boy (patient) in permanent dentition with its
      management along with the radiographic investigations and photographic
      presentations of the other members of his family affected with this condition.

PMID- 23536621
TI  - A retained pulmonary artery catheter fragment incidentally found lodged in the
      right heart 16 years after its insertion.
AB  - Sixteen years after a long admission for a serious occupational accident, a 38
      year-old man presented with intermittent atypical chest pain. Upon investigations
      a retained fragment of a pulmonary artery catheter was found in the right
      ventricle. Throughout the years between his accident and the current presentation
      he did not have any symptoms or signs of complications associated with the
      retained catheter such as arrhythmia, sepsis or thromboembolism. Upon presenting
      his case at the medical/surgical multidisciplinary meeting it was decided that
      the probability of complications occurring at this stage was low as the catheter
      fragment would have endothelialised and the risk of retrieval would outweigh the
      benefits. This scenario highlighted the importance of understanding the possible
      long-term complications of retained catheter fragments, the importance of being
      aware of the limitation of these devices and the need to be more vigilant in the
      emergency setting.

PMID- 23536622
TI  - Vitamin B12 deficiency presenting as acute ataxia.
AB  - A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of
      acute ataxia and failure to thrive, initially suspicious for an intracranial
      mass. Weight and body mass index were below the third percentile and he
      demonstrated loss of joint position and vibratory sense on examination.
      Laboratory studies revealed megaloblastic anaemia while an initial MRI of the
      brain showed no evidence of mass lesions or other abnormalities. A dietary
      history revealed the child subscribed to a restrictive vegan diet with little to
      no intake of animal products or other fortified foods. The child was diagnosed
      with presumed vitamin B12 deficiency and was treated with intramuscular B12
      injections. Neurological symptoms resolved promptly within several days after
      starting therapy. This case underlines the importance of assessing nutritional
      status in the evaluation of neurological dysfunction in the pediatric patient.

PMID- 23536623
TI  - Renal calculi with retrocaval ureter: is percutaneous nephrolithotomy sufficient?
AB  - A 60-year-old woman presented with complaints of intermittent right flank pain
      which had begun one year ago. Ultrasonography and intravenous urogram showed
      right pelvic (15 mm) and inferior calyceal (6 mm) calculi along with suspected
      retrocaval course of right ureter, which was confirmed by contrast CT scan. Tc
      99m diethylene-triamine-penta-acetic acid (DTPA) scan showed normal function and
      normal drainage of right kidney. Percutaneous nephrolithotomy (PCNL) was
      performed for right renal calculi. Because of curved ureteric course, negotiation
      of ureteric catheter in pelvis was anticipated to be troublesome, so
      intraoperative retrograde pyelogram (RGP) was performed to delineate the anatomy.
      Puncture was performed safely after air contrast pyelography. No complications
      occurred intraoperatively and postoperatively. On follow-up of up to 1 year
      patient was asymptomatic and renal scan showed normal function and drainage. So
      in the presence of retrocaval ureter and associated renal calculi, PCNL is a safe
      and optimal procedure and in condition of non-obstructive drainage, management of
      calculi only is adequate.

PMID- 23536624
TI  - Angiolipoma: rare cause of adult ileoileal intussusception.
AB  - Intussusception in adults is rare and more common in the paediatric population.
      Clinically, most adult patients have chronic non-specific symptoms due to partial
      obstruction. In contrast, most paediatric patients present with the classic triad
      of abdominal pain, vomiting and blood in stool. Adult intussusception is commonly
      associated with an organic aetiology, most likely a benign or malignant neoplasm
      as a lead point of intussusception. We describe a case of a 29-year-old woman
      with subacute presentation due to ileoileal intussusception secondary to a
      polypoid submucosal angiolipoma. Angiolipoma is a benign lesion composed of
      mature adipose tissue and thin-walled capillaries. The presence of thin-walled
      vessels differentiates it from a lipoma. Angiolipomas of the small intestine are
      extremely rare with very few reported cases. This case not only demonstrates an
      unusual benign lesion as a cause of intussusception, but also illustrates an
      atypical clinical presentation in adults with intussusception.

PMID- 23536625
TI  - Piriformis syndrome occurring after pregnancy.

PMID- 23536626
TI  - Intractable intraoperative bleeding requiring platelet transfusion during
      emergent cholecystectomy in a patient with dual antiplatelet therapy after drug
      eluting coronary stent implantation (with video).
AB  - We report a case of a 76-year-old man, receiving dual antiplatelet therapy (DAPT)
      with aspirin and ticlopidine for the past 6 years after implantation of drug
      eluting coronary stent, developed a severe hypochondriac pain. After diagnosing
      severe acute cholecystitis by an enhanced CT, emergent laparotomy under
      continuation of DAPT was attempted. During the operation, intractable bleeding
      from the adhesiolysed liver surface was encountered, which required platelet
      transfusion. Subtotal cholecystectomy with abdominal drainage was performed, and
      the patient recovered without any postoperative bleeding or thromboembolic
      complications. Like the present case, the final decision should be made to
      perform platelet transfusion when life-threatening DAPT-induced intraoperative
      bleeding occurs during an emergent surgery, despite the elevated risk of stent
      thrombosis.

PMID- 23536627
TI  - Pregnancy after hydrosalpinx treatment with Essure.
AB  - We present a case of a 29-year-old woman, with a history of ectopic pregnancy,
      which required left salpingectomy, and with a tortuous and impermeable right
      fallopian tube, compatible with hydrosalpinx. As hydrosalpinx itself can
      compromise a future pregnancy, treatment with Essure was proposed before passing
      to medically assisted procreation techniques. Five months after placement of
      Essure in the right fallopian tube, an in vitro fertilisation cycle was
      successfully completed and the woman had a singleton pregnancy and vaginal
      delivery without intercurrences.

PMID- 23536628
TI  - IL-27 receptor signaling regulates CD4+ T cell chemotactic responses during
      infection.
AB  - IL-27 exerts pleiotropic suppressive effects on naive and effector T cell
      populations during infection and inflammation. Surprisingly, however, the role of
      IL-27 in restricting or shaping effector CD4(+) T cell chemotactic responses, as
      a mechanism to reduce T cell-dependent tissue inflammation, is unknown. In this
      study, using Plasmodium berghei NK65 as a model of a systemic, proinflammatory
      infection, we demonstrate that IL-27R signaling represses chemotaxis of infection
      derived splenic CD4(+) T cells in response to the CCR5 ligands, CCL4 and CCL5.
      Consistent with these observations, CCR5 was expressed on significantly higher
      frequencies of splenic CD4(+) T cells from malaria-infected, IL-27R-deficient
      (WSX-1(-/-)) mice than from infected wild-type mice. We find that IL-27 signaling
      suppresses splenic CD4(+) T cell CCR5-dependent chemotactic responses during
      infection by restricting CCR5 expression on CD4(+) T cell subtypes, including Th1
      cells, and also by controlling the overall composition of the CD4(+) T cell
      compartment. Diminution of the Th1 response in infected WSX-1(-/-) mice in vivo
      by neutralization of IL-12p40 attenuated CCR5 expression by infection-derived
      CD4(+) T cells and also reduced splenic CD4(+) T cell chemotaxis toward CCL4 and
      CCL5. These data reveal a previously unappreciated role for IL-27 in modulating
      CD4(+) T cell chemotactic pathways during infection, which is related to its
      capacity to repress Th1 effector cell development. Thus, IL-27 appears to be a
      key cytokine that limits the CCR5-CCL4/CCL5 axis during inflammatory settings.

PMID- 23536629
TI  - Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation.
AB  - The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate
      decisions, but the molecular mechanism underpinning this regulation is unclear.
      In this study we show that loss of Id2 cripples effector differentiation and
      instead programs CD8(+) T cells to adopt a memory fate with increased
      Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell
      memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and
      that Id2 expression level mirrors T cell memory recall capacity. As a result of
      the defective effector differentiation, Id2-deficient CD8(+) T cells fail to
      induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T
      cells. Our findings reveal that the Id2/E2A axis orchestrates T cell
      differentiation through the induction or repression of downstream transcription
      factors essential for effector and memory T cell differentiation.

PMID- 23536631
TI  - GITR-dependent regulation of 4-1BB expression: implications for T cell memory and
      anti-4-1BB-induced pathology.
AB  - The TNFR family member 4-1BB plays a key role in the survival of activated and
      memory CD8 T cells. However, the mechanisms that regulate 4-1BB re-expression on
      memory CD8 T cells after Ag clearance are unknown. In unimmunized mice, ~10% of
      CD8 CD44(hi) memory T cells in the bone marrow (BM) and liver express 4-1BB, with
      minimal 4-1BB expression in spleen and lymph node. IL-2, IL-15, and IL-7 are
      collectively dispensable for 4-1BB expression on the memory CD8 T cells. Rather,
      T cell-intrinsic glucocorticoid-induced TNFR-related protein (GITR) contributes
      to 4-1BB expression on CD8 T cells upon their entry into the BM or liver.
      Consistent with its role in regulation of 4-1BB, GITR is required on memory CD8 T
      cells for their persistence in vivo. These findings reveal site-specific effects
      of the BM and liver microenvironment on CD8 memory T cells. Previous work has
      demonstrated that 4-1BB agonists given to unimmunized mice induce splenomegaly,
      hepatitis, and other immune system anomalies. Moreover, severe liver pathology
      has been observed in a subset of anti-4-1BB-treated melanoma patients.
      Remarkably, the absence of GITR in mice almost completely abrogates cellular
      expansions, splenomegaly, and liver inflammation associated with anti-4-1BB
      agonist treatment of unimmunized mice. In contrast, lack of CD8 T cells
      selectively improves liver pathology, but not splenomegaly in the mice. Thus, the
      regulation of 4-1BB expression by GITR on CD8 T cells, as well as on other cells,
      contributes to the pathological effects of anti-4-1BB in unimmunized mice.

PMID- 23536630
TI  - Prenatally acquired vitamin A deficiency alters innate immune responses to human
      rotavirus in a gnotobiotic pig model.
AB  - We examined how prenatally acquired vitamin A deficiency (VAD) modulates innate
      immune responses and human rotavirus (HRV) vaccine efficacy in a gnotobiotic (Gn)
      piglet model of HRV diarrhea. The VAD and vitamin A-sufficient (VAS) Gn pigs were
      vaccinated with attenuated HRV (AttHRV) with or without concurrent oral vitamin A
      supplementation (100,000 IU) and challenged with virulent HRV (VirHRV).
      Regardless of vaccination status, the numbers of conventional and plasmacytoid
      dendritic cells (cDCs and pDCs) were higher in VAD piglets prechallenge, but
      decreased substantially postchallenge as compared with VAS pigs. We observed
      significantly higher frequency of CD103 (integrin alphaEbeta7) expressing DCs in
      VAS versus VAD piglets postchallenge, indicating that VAD may interfere with
      homing (including intestinal) phenotype acquisition. Post-VirHRV challenge, we
      observed longer and more pronounced diarrhea and higher VirHRV fecal titers in
      nonvaccinated VAD piglets. Consistent with higher VirHRV shedding titers, higher
      IFN-alpha levels were induced in control VAD versus VAS piglet sera at
      postchallenge day 2. Ex vivo HRV-stimulated mononuclear cells (MNCs) isolated
      from spleen and blood of VAD pigs prechallenge also produced more IFN-alpha. In
      contrast, at postchallenge day 10, we observed reduced IFN-alpha levels in VAD
      pigs that coincided with decreased TLR3(+) MNC frequencies. Numbers of necrotic
      MNCs were higher in VAD pigs in spleen (coincident with splenomegaly in other VAD
      animals) prechallenge and intestinal tissues (coincident with higher VirHRV
      induced intestinal damage) postchallenge. Thus, prenatal VAD caused an imbalance
      in innate immune responses and exacerbated VirHRV infection, whereas vitamin A
      supplementation failed to compensate for these VAD effects.

PMID- 23536632
TI  - Platelet induction of the acute-phase response is protective in murine
      experimental cerebral malaria.
AB  - Platelets are most recognized as the cellular mediator of thrombosis, but they
      are increasingly appreciated for their immunomodulatory roles, including
      responses to Plasmodium infection. Platelet interactions with endothelial cells
      and leukocytes contribute significantly to the pathogenesis of experimental
      cerebral malaria (ECM). Recently, it has been suggested that platelets not only
      have an adverse role in cerebral malaria, but platelets may also be protective in
      animal models of uncomplicated malaria. We now demonstrate that these diverse and
      seemingly contradictory roles for platelets extend to cerebral malaria models and
      are dependent on the timing of platelet activation during infection. Our data
      show that platelets are activated very early in ECM and have a central role in
      initiation of the acute-phase response to blood-stage infection. Unlike platelet
      depletion or inhibition postinfection, preinfection platelet depletion or
      treatment with a platelet inhibitor is not protective. Additionally, we show that
      platelet-driven acute-phase responses have a major role in protecting mice from
      ECM by limiting parasite growth. Our data now suggest that platelets have a
      complex role in ECM pathogenesis: platelets help limit parasite growth early
      postinfection, but with continued platelet activation as the disease progresses,
      platelets contribute to ECM-associated inflammation.

PMID- 23536633
TI  - Role of fatty-acid synthesis in dendritic cell generation and function.
AB  - Dendritic cells (DC) are professional APCs that regulate innate and adaptive
      immunity. The role of fatty-acid synthesis in DC development and function is
      uncertain. We found that blockade of fatty-acid synthesis markedly decreases
      dendropoiesis in the liver and in primary and secondary lymphoid organs in mice.
      Human DC development from PBMC precursors was also diminished by blockade of
      fatty-acid synthesis. This was associated with higher rates of apoptosis in
      precursor cells and increased expression of cleaved caspase-3 and BCL-xL and
      downregulation of cyclin B1. Further, blockade of fatty-acid synthesis decreased
      DC expression of MHC class II, ICAM-1, B7-1, and B7-2 but increased their
      production of selected proinflammatory cytokines including IL-12 and MCP-1.
      Accordingly, inhibition of fatty-acid synthesis enhanced DC capacity to activate
      allogeneic as well as Ag-restricted CD4(+) and CD8(+) T cells and induce CTL
      responses. Further, blockade of fatty-acid synthesis increased DC expression of
      Notch ligands and enhanced their ability to activate NK cell immune phenotype and
      IFN-gamma production. Because endoplasmic reticulum (ER) stress can augment the
      immunogenic function of APC, we postulated that this may account for the higher
      DC immunogenicity. We found that inhibition of fatty-acid synthesis resulted in
      elevated expression of numerous markers of ER stress in humans and mice and was
      associated with increased MAPK and Akt signaling. Further, lowering ER stress by
      4-phenylbutyrate mitigated the enhanced immune stimulation associated with fatty
      acid synthesis blockade. Our findings elucidate the role of fatty-acid synthesis
      in DC development and function and have implications to the design of DC vaccines
      for immunotherapy.

PMID- 23536634
TI  - Nonstereotyped lymphoma B cell receptors recognize vimentin as a shared
      autoantigen.
AB  - Ag activation of the BCR may play a role in the pathogenesis of human follicular
      lymphoma (FL) and other B cell malignancies. However, the nature of the Ag(s)
      recognized by tumor BCRs has not been well studied. In this study, we used
      unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL Igs
      recognized vimentin as a shared autoantigen. The epitope was localized to the N
      terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed
      specific binding to vimentin by using recombinant vimentin and by performing
      competitive inhibition studies. Furthermore, using indirect immunofluorescence
      staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti
      vimentin mAb in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs
      was significantly higher than that of IgM FL Igs (30.4 versus 10%; p = 0.0022).
      However, vimentin-reactive FL Igs did not share CDR3 motifs and were not
      homologous. Vimentin was expressed in the T cell-rich regions of FL, suggesting
      that vimentin is available for binding with tumor BCRs within the tumor
      microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma
      and multiple myeloma Igs. Our results demonstrate that vimentin is a shared
      autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle cell
      lymphoma and multiple myeloma and suggest that vimentin may play a role in the
      pathogenesis of multiple B cell malignancies. These findings may lead to a better
      understanding of the biology and natural history of FL and other B cell
      malignancies.

PMID- 23536635
TI  - Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to
      Processing and Presentation by Recipient APCs.
AB  - Modification of allogeneic dendritic cells (DCs) through drug treatment results
      in DCs with in vitro hallmarks of tolerogenicity. Despite these observations,
      using murine MHC-mismatched skin and heart transplant models, donor-derived drug
      modified DCs not only failed to induce tolerance but also accelerated graft
      rejection. The latter was inhibited by injecting the recipient with anti-CD8 Ab,
      which removed both CD8(+) T cells and CD8(+) DCs. The discrepancy between in
      vitro and in vivo data could be explained, partly, by the presentation of drug
      modified donor DC MHC alloantigens by recipient APCs and activation of recipient
      T cells with indirect allospecificity, leading to the induction of
      alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug-treated
      DCs were rapidly processed and presented in peptide form by recipient APCs in
      vivo within hours of DC injection. Using TCR-transgenic T cells, Ag presentation
      of injected OVA-pulsed DCs was detectable for <= 3 d, whereas indirect
      presentation of MHC alloantigen by recipient APCs led to activation of T cells
      within 14 h and was partially inhibited by reducing the numbers of CD8(+) DCs in
      vivo. In support of this observation when mice lacking CD8(+) DCs were pretreated
      with drug-modified DCs prior to transplantation, skin graft rejection kinetics
      were similar to those in non-DC-treated controls. Of interest, when the same mice
      were treated with anti-CD40L blockade plus drug-modified DCs, skin graft survival
      was prolonged, suggesting endogenous DCs were responsible for T cell priming.
      Altogether, these findings highlight the risks and limitations of negative
      vaccination using alloantigen-bearing "tolerogenic" DCs.

PMID- 23536637
TI  - Mast cell FcepsilonRI-induced early growth response 2 regulates CC chemokine
      ligand 1-dependent CD4+ T cell migration.
AB  - Mast cells are well positioned in host tissue for detecting environmental
      signals, including allergens, leading to activation of the high-affinity IgE
      receptor FcepsilonRI, and initiating a signaling cascade that perpetuates the
      production of biologically potent mediators, including chemokines. We have
      identified a novel target of mast cell FcepsilonRI activity in the transcription
      factor early growth response 2 (Egr2) and sought to characterize its function
      therein. Egr2 was transiently activated following FcepsilonRI-mediated signaling,
      targeted the promoter of the chemokine CCL1, and was critical for allergen
      induced mast cell CCL1 production. Egr2-deficient mast cells were incapable of
      directing CD4(+) T cell migration via the CCL1-CCR8 axis. In a model of allergic
      asthma, reconstitution of mast cell-deficient mice with Egr2-deficient mast cells
      demonstrated that mast cell Egr2 was essential for migration of CD4(+) T cells to
      the inflamed lung. These findings position Egr2 as a critical regulator of mast
      cell-directed CD4(+) T cell migration.

PMID- 23536636
TI  - Restoring immune function of tumor-specific CD4+ T cells during recurrence of
      melanoma.
AB  - Recurrent solid malignancies are often refractory to standard therapies. Although
      adoptive T cell transfer may benefit select individuals, the majority of patients
      succumb to their disease. To address this important clinical dilemma, we
      developed a mouse melanoma model in which initial regression of advanced disease
      was followed by tumor recurrence. During recurrence, Foxp3(+) tumor-specific
      CD4(+) T cells became PD-1(+) and represented >60% of the tumor-specific CD4(+) T
      cells in the host. Concomitantly, tumor-specific CD4(+) T effector cells showed
      traits of chronic exhaustion, as evidenced by their high expression of the PD-1,
      TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD
      1/PD-L1 pathway with anti-PD-L1 Abs or depletion of tumor-specific regulatory T
      cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1
      blockade with tumor-specific Treg depletion effectively mediated disease
      regression. Furthermore, blockade with a combination of anti-PD-L1 and anti-LAG-3
      Abs overcame the requirement to deplete tumor-specific Tregs. In contrast,
      successful treatment of primary melanoma with adoptive cell therapy required only
      Treg depletion or Ab therapy, underscoring the differences in the characteristics
      of treatment between primary and relapsing cancer. These data highlight the need
      for preclinical development of combined immunotherapy approaches specifically
      targeting recurrent disease.

PMID- 23536638
TI  - Circulating fibrocytes prepare the lung for cancer metastasis by recruiting Ly
      6C+ monocytes via CCL2.
AB  - Fibrocytes are circulating, hematopoietic cells that express CD45 and Col1a1.
      They contribute to wound healing and several fibrosing disorders by mechanisms
      that are poorly understood. In this report, we demonstrate that fibrocytes
      predispose the lung to B16-F10 metastasis by recruiting Ly-6C(+) monocytes. To do
      so, we isolated fibrocytes expressing CD45, CD11b, CD13, and Col1a1 from the
      lungs of wild type (WT) and Ccr5(-/-) mice. WT but not Ccr5(-/-) fibrocytes
      increased the number of metastatic foci when injected into Ccr5(-/-) mice (73 +/-
      2 versus 32 +/- 5; p < 0.001). This process was MMP9 dependent. Injection of WT
      enhanced GFP(+) fibrocytes also increased the number of Gr-1(Int), CD11b(+), and
      enhanced GFP(-) monocytes. Like premetastatic-niche monocytes, these recruited
      cells expressed Ly-6C, CD117, and CD45. The transfer of these cells into Ccr5(-/
      ) mice enhanced metastasis (90 +/- 8 foci) compared with B cells (27 +/- 2),
      immature dendritic cells (31 +/- 6), or alveolar macrophages (28 +/- 3; p <
      0.05). WT and Ccl2(-/-) fibrocytes also stimulated Ccl2 expression in the lung by
      2.07 +/- 0.05- and 2.78 +/- 0.36-fold compared with Ccr5(-/-) fibrocytes (1.0 +/-
      0.06; p < 0.05). Furthermore, WT fibrocytes did not increase Ly-6C(+) monocytes
      in Ccr2(-/-) mice and did not promote metastasis in either Ccr2(-/-) or Ccl2(-/-)
      mice. These data support our hypothesis that fibrocytes contribute to
      premetastatic conditioning by recruiting Ly-6C(+) monocytes in a chemokine
      dependent process. This work links metastatic risk to conditions that mobilize
      fibrocytes, such as inflammation and wound repair.

PMID- 23536639
TI  - Risk factors for severe adverse effects and treatment-related deaths in Japanese
      patients treated with irinotecan-based chemotherapy: a postmarketing survey.
AB  - OBJECTIVES: This analysis was conducted to clarify risk factors for severe
      adverse effects and treatment-related deaths reported during a postmarketing
      survey of irinotecan. METHODS: The survey covered all patients treated with
      irinotecan in Japan between April 1995 and January 2000. The patient background
      data and adverse drug reactions were collected through case report forms.
      Univariate and multivariate logistic regression analyses including 14 explanatory
      variables were performed to determine the risk factors for grade 3-4 leukopenia,
      thrombocytopenia and diarrhea for all patients and subgroups with five major
      cancers. Treatment-related deaths were also analyzed. RESULTS: Case report forms
      of 13 935 patients (94.1% of 14 802 patients registered) treated with irinotecan
      based chemotherapy were collected. Major grade 3-4 adverse drug reactions were
      leukopenia (34.8%), thrombocytopenia (12.4%) and diarrhea (10.1%). Multivariate
      analysis revealed that the risk factors (odds ratio >=1.5) common for all these
      three adverse drug reactions were performance status (>=3), infection and renal
      dysfunction before starting irinotecan therapy. Additionally, the risk factors
      for leukopenia were being female and prior radiotherapy, those for
      thrombocytopenia were age (>=65 years), while those for diarrhea were pleural
      effusion and watery stool. The risk factors in each cancer were also identified.
      The incidence of treatment-related death was 1.3% (176). Myelosuppression-related
      deaths accounted for 70% and interstitial lung disease for 11% of all treatment
      related deaths. Being male, age, performance status >=3, massive ascites and
      infection and renal dysfunction were identified as risk factors for treatment
      related death. CONCLUSIONS: To ensure the safety of irinotecan therapy, it is
      important to select appropriate patients by considering the risk factors.

PMID- 23536640
TI  - Intestine-specific expression of MOGAT2 partially restores metabolic efficiency
      in Mogat2-deficient mice.
AB  - Acyl CoA:monoacylglycerol acyltransferase (MGAT) catalyzes the resynthesis of
      triacylglycerol, a crucial step in the absorption of dietary fat. Mice lacking
      the gene Mogat2, which codes for an MGAT highly expressed in the small intestine,
      are resistant to obesity and other metabolic disorders induced by high-fat
      feeding. Interestingly, these Mogat2-/- mice absorb normal amounts of dietary fat
      but exhibit a reduced rate of fat absorption, increased energy expenditure,
      decreased respiratory exchange ratio, and impaired metabolic efficiency. MGAT2 is
      expressed in tissues besides intestine. To test the hypothesis that intestinal
      MGAT2 enhances metabolic efficiency and promotes the storage of metabolic fuels,
      we introduced the human MOGAT2 gene driven by the intestine-specific villin
      promoter into Mogat2-/- mice. We found that the expression of MOGAT2 in the
      intestine increased intestinal MGAT activity, restored fat absorption rate,
      partially corrected energy expenditure, and promoted weight gain upon high-fat
      feeding. However, the changes in respiratory exchange ratio were not reverted,
      and the recoveries in metabolic efficiency and weight gain were incomplete. These
      data indicate that MGAT2 in the intestine plays an indispensable role in
      enhancing metabolic efficiency but also raise the possibility that MGAT2 in other
      tissues may contribute to the regulation of energy metabolism.

PMID- 23536641
TI  - Atypical distribution of pneumatosis intestinalis in a patient with AIDS.
AB  - An adult patient who had AIDS was admitted to hospital following a fall in which
      they sustained a T12 vertebral fracture. The patient incidentally was found to
      have pneumatosis intestinalis upon a thoracolumbar radiograph taken approximately
      2 weeks after their admission to the hospital. At this point in time the patient
      reported having diarrhoea and a distended abdomen. The patient did not have any
      other medical history of note. Upon examination the patient appeared comfortable.
      The patient's abdomen was distended but soft and non-tender. Laboratory
      investigations revealed a chronic normocytic anaemia and neutropenia. It was
      likely that the pneumatosis intestinalis was AIDS related. A CT scan confirmed
      its presence but revealed an atypical distribution. Despite its dramatic
      appearance, the patient was successfully managed conservatively and remained well
      during admission.

PMID- 23536642
TI  - Nasopalatine canal cyst: often missed.
AB  - Nasopalatine canal cyst may occur within the nasopalatine canal or in the soft
      tissues of the palate, at the opening of the canal, where it is called the 'cyst
      of the palatine papilla'. These are normally asymptomatic, constituting casual
      radiological findings. We present a case report of a male patient with infected
      nasopalatine canal cyst seen clinically as swelling over palate. Radiographic
      interpretation should be thoroughly performed for maxillary anterior region and
      any occlusal radiograph in routine radiography to screen this entity and must be
      distinguished from other maxillary anterior radiolucencies by the clinician.

PMID- 23536643
TI  - Unexpected hypozincaemia in a patient with discharging empyema that proved
      resistant to replacement therapy.
AB  - A 45-year-old man was admitted with a massive discharging empyema. He had severe
      chronic malnutrition and was noted to be zinc and selenium deficient. A high
      calorie oral diet supplemented with iron, zinc and selenium was started, together
      with antibiotic therapy and continued prescription of the patient's regular
      medication, including a PPI (proton pump inhibitor). Although selenium increased
      to normal levels after 4 weeks of supplementation, zinc levels failed to
      normalise. Antibiotic therapy improved the empyema and a steady increase in
      weight was achieved. The patient was noted to have erythematous skin lesions,
      hair loss and reduced wound healing, all of which may be attributable to zinc
      deficiency. We propose that competition for intestinal absorption of nutrients
      and the use of a PPI may have covertly contributed to the inability to normalise
      serum zinc levels in this case.

PMID- 23536644
TI  - When less is more: a case of phenytoin toxicity.
AB  - The authors present a case of an 87-year-old gentleman who presented with general
      deterioration, increased confusion, recurrent falls and unsteadiness. He was
      treated for a urinary tract infection but was found to deteriorate rapidly,
      developing bilateral nystagmus, marked pastpointing, dysarthria and central
      ataxia. He had a complex medical history including epilepsy controlled with long
      term phenytoin. Phenytoin is 90% protein bound and displaced by bilirubin. At the
      time of deterioration his total phenytoin concentration was within the limits of
      the laboratory's recommended therapeutic range. The biochemistry report also
      denoted the patient was hypoalbuminaemic and hyperbilirubinaemic. His symptoms
      completely resolved with phenytoin dose reduction. The combination of low albumin
      and high bilirubin may cause an increase in the free phenytoin concentration,
      resulting in toxicity, despite the measured total phenytoin concentration being
      within the therapeutic interval.

PMID- 23536646
TI  - Ultrasound guided V3 segment vertebral artery direct percutaneous puncture for
      basilar artery mechanical thrombectomy in acute stroke: a technical report.
AB  - A middle aged patient presented with acute ischemic stroke due to basilar artery
      occlusion. The patient clinically deteriorated despite intravenous thrombolysis
      and was referred for mechanical thrombectomy. The right vertebral artery was
      occluded and could not be accessed despite attempting various shaped catheters,
      even when a radial artery access was used. The left vertebral artery ended in the
      posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment
      vertebral artery direct puncture was successfully done and the procedure was
      completed. No access related complications were encountered. Direct cervical
      arterial puncture can be safely used by experienced operators as a last resort in
      acute stroke cases with difficult access.

PMID- 23536645
TI  - Salvage of distal non-target coil embolization with stent placement and
      intravenous eptifibatide in a ruptured, unsecured, atypical aneurysm.
AB  - INTRODUCTION: Small aneurysms may be challenging to embolize. In cases of
      subarachnoid hemorrhage (SAH) where treatment is delayed, physicians may have to
      balance the risks of certain required therapies (antiplatelet agents) with the
      risk of rerupture. We describe a case of a technically challenging anterior
      cerebral artery aneurysm requiring eptifibatide infusion prior to definitive
      aneurysm treatment. CASE REPORT: A 57-year-old woman with SAH, underwent coil
      embolization of a small fenestrated A1-A2 junction aneurysm. The procedure was
      complicated by downstream coil migration which was then treated with Enterprise
      stent placement in the pericallosal artery. This required subsequent infusion of
      a glycoprotein IIb/IIIa inhibitor until the aneurysm could be repaired
      surgically. CONCLUSIONS: Revascularization with a stent in a distal cerebral
      vessel may salvage inadvertent coil migration. Although it is undesirable to
      administer antiplatelet agents to patients with SAH, in these circumstances short
      acting agents may be used.

PMID- 23536647
TI  - A silent acute abdomen in a patient with spinal cord injury.
AB  - A 52-year-old man with cervical spondylosis sustained a hyperextension injury to
      the neck and subsequently developed central cord syndrome after 2 weeks. The
      diagnosis was confirmed clinically and on MRI. During the admission he was
      febrile from Streptococcus anginosus bacteraemia from a gum infection and was
      started on penicillin. This resulted in pseudomembranous colitis with abdominal
      distension and bloody diarrhoea but a lack of expected abdominal complaints.
      Unfortunately his neurology deteriorated and a repeat MRI showed a discitis at C5
      C7 which required a 2-level discectomy, debridement and instrumented fusion.
      Owing to his spinal cord injury, an abdominal perforation was initially missed
      owing to the lack of clinical features of an acute abdomen. He underwent a right
      hemi-colectomy for ascending colon perforation and eventually made a good
      recovery and was discharged to a spinal rehabilitation unit. By one year follow
      up he had returned to full neurological function.

PMID- 23536648
TI  - Campylobacter fetus sepsis in an immunocompetent patient with haematological
      complication.
AB  - Campylobacter fetus sepsis is rare, especially among young, immunocompetent
      patients. We present the case of a 43-year-old man with a history of ulcerative
      colitis who was diagnosed with C fetus bacteraemia with endovascular
      manifestation. The patient was found to have a low vitamin K level and a high
      international normalised ratio, and developed deep vein thrombosis. The patient
      was fully recovered with oral antibiotic treatment, anticoagulation and
      supportive therapy. Clinicians should be aware that this type of infection,
      although extremely rare, can occur even in younger, healthy adults and immediate
      diagnosis and treatment are required to avert life-threatening complications.

PMID- 23536649
TI  - Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in
      prostate cancer.
AB  - Androgen receptor (AR) signaling is critical for the tumorigenesis and
      development of prostate cancer, as well as the progression to castration
      resistant prostate cancer. We previously showed that the heterochromatin protein
      1 (HP1) beta isoform plays a critical role in transactivation of AR signaling as
      an AR coactivator that promotes prostate cancer cell proliferation. However, the
      roles of other HP1 isoforms, HP1alpha and HP1gamma, in AR expression and prostate
      cancer remain unclear. Here, we found that knockdown of HP1gamma, but not
      HP1alpha, reduced AR expression and cell proliferation by inducing cell cycle
      arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length
      HP1alpha and its C-terminal deletion mutant increased AR expression and cell
      growth, whereas overexpression of HP1gamma had no effect. Similarly, HP1alpha
      overexpression promoted 22Rv1 cell growth, whereas HP1gamma knockdown reduced the
      proliferation of CxR cells, a castration-resistant LNCaP derivative. Taken
      together, HP1 isoforms distinctly augment AR signaling and cell growth in
      prostate cancer. Therefore, silencing of HP1beta and HP1gamma may be a promising
      therapeutic strategy for treatment of prostate cancer.

PMID- 23536650
TI  - Rat Gnrhr promoter directs species-specific gene expression in the pituitary and
      testes of transgenic mice.
AB  - The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably
      in gonads. However, mechanisms underlying the gonad-specific expression of Gnrhr
      are not well understood. Here, Gnrhr expression was analysed in the developing
      testes and pituitaries of rats and transgenic mice bearing the human placental
      alkaline phosphatase reporter gene (ALPP) under the control of the rat Gnrhr
      promoter. We showed that the 3.3 kb, but not the pituitary-specific 1.1 kb
      promoter, directs ALPP expression exclusively to testis Leydig cells from
      embryonic day 12 onwards. Real-time PCR analysis revealed that promoter activity
      displayed the same biphasic profile as marker genes in Leydig cells, i.e. abrupt
      declines after birth followed by progressive rises after a latency phase, in
      coherence with the differentiation and evolution of foetal and adult Leydig cell
      lineages. Interestingly, the developmental profile of transgene expression showed
      high similarity with the endogenous Gnrhr profile in the rat testis, while mouse
      Gnrhr was only poorly expressed in the mouse testis. In the pituitary, both
      transgene and Gnrhr were co-expressed at measurable levels with similar
      ontogenetic profiles, which were markedly distinct from those in the testis.
      Castration that induced pituitary Gnrhr up-regulation in rats did not affect the
      mouse Gnrhr. However, it duly up-regulated the transgene. In addition, in LbetaT2
      cells, the rat, but not mouse, Gnrhr promoter was sensitive to GnRH agonist
      stimulation. Collectively, our data highlight inter-species variations in the
      expression and regulation of Gnrhr in two different organs and reveal that the
      rat promoter sequence contains relevant genetic information that dictates rat
      specific gene expression in the mouse context.

PMID- 23536651
TI  - TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell
      entry and is expressed in viral target cells in the respiratory epithelium.
AB  - Infection with human coronavirus 229E (HCoV-229E) is associated with the common
      cold and may result in pneumonia in immunocompromised patients. The viral spike
      (S) protein is incorporated into the viral envelope and mediates infectious entry
      of HCoV-229E into host cells, a process that depends on the activation of the S
      protein by host cell proteases. However, the proteases responsible for HCoV-229E
      activation are incompletely defined. Here we show that the type II transmembrane
      serine proteases TMPRSS2 and HAT cleave the HCoV-229E S-protein (229E-S) and
      augment 229E-S-driven cell-cell fusion, suggesting that TMPRSS2 and HAT can
      activate 229E-S. Indeed, engineered expression of TMPRSS2 and HAT rendered 229E-S
      driven virus-cell fusion insensitive to an inhibitor of cathepsin L, a protease
      previously shown to facilitate HCoV-229E infection. Inhibition of endogenous
      cathepsin L or TMPRSS2 demonstrated that both proteases can activate 229E-S for
      entry into cells that are naturally susceptible to infection. In addition,
      evidence was obtained that activation by TMPRSS2 rescues 229E-S-dependent cell
      entry from inhibition by IFITM proteins. Finally, immunohistochemistry revealed
      that TMPRSS2 is coexpressed with CD13, the HCoV-229E receptor, in human airway
      epithelial (HAE) cells, and that CD13(+) TMPRSS2(+) cells are preferentially
      targeted by HCoV-229E, suggesting that TMPRSS2 can activate HCoV-229E in infected
      humans. In sum, our results indicate that HCoV-229E can employ redundant
      proteolytic pathways to ensure its activation in host cells. In addition, our
      observations and previous work suggest that diverse human respiratory viruses are
      activated by TMPRSS2, which may constitute a target for antiviral intervention.

PMID- 23536652
TI  - Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of
      hepatitis C virus genotype 1-infected patients.
AB  - The preeminent mode of action of the broad-spectrum antiviral nucleoside
      ribavirin in the therapy of chronic hepatitis C is currently unresolved.
      Particularly under contest are possible mutagenic effects of ribavirin that may
      lead to viral extinction by lethal mutagenesis of the hepatitis C virus (HCV)
      genome. We applied ultradeep sequencing to determine ribavirin-induced sequence
      changes in the HCV coding region (nucleotides [nt] 330 to 9351) of patients
      treated with 6-week ribavirin monotherapy (n = 6) in comparison to placebo (n =
      6). Baseline HCV RNA levels maximally declined on average by -0.8 or -0.1 log10
      IU/ml in ribavirin- versus placebo-treated patients. No general increase in rates
      of nucleotide substitutions in ribavirin-treated patients was observed. However,
      more HCV genome positions with high G-to-A and C-to-U transition rates were
      detected between baseline and treatment week 6 in ribavirin-treated patients in
      comparison to placebo-treated patients (rate of 0.0041 transitions per base pair
      versus rate of 0.0022 transitions per base pair; P = 0.049). Similarly, the
      sensitive detection of low-frequency minority variants by statistical filtering
      indicated significantly more positions with G-to-A and C-to-U transitions in
      ribavirin-treated patients than in placebo-treated patients (rate of 0.0331
      transitions versus rate of 0.0186 transitions per G/C-containing position at
      baseline; P = 0.018). In contrast, non-ribavirin-associated A-to-G and U-to-C
      transitions were not enriched in the ribavirin group (P = 0.152). We conclude
      that ribavirin exerts a mutagenic effect on the virus in patients with chronic
      hepatitis C by facilitating G-to-A and C-to-U nucleotide transitions.

PMID- 23536653
TI  - The cellular decapping activators LSm1, Pat1, and Dhh1 control the ratio of
      subgenomic to genomic Flock House virus RNAs.
AB  - Positive-strand RNA viruses depend on recruited host factors to control critical
      replication steps. Previously, it was shown that replication of evolutionarily
      diverse positive-strand RNA viruses, such as hepatitis C virus and brome mosaic
      virus, depends on host decapping activators LSm1-7, Pat1, and Dhh1 (J. Diez et
      al., Proc. Natl. Acad. Sci. U. S. A. 97:3913-3918, 2000; A. Mas et al., J. Virol.
      80:246 -251, 2006; N. Scheller et al., Proc. Natl. Acad. Sci. U. S. A. 106:13517
      13522, 2009). By using a system that allows the replication of the insect Flock
      House virus (FHV) in yeast, here we show that LSm1-7, Pat1, and Dhh1 control the
      ratio of subgenomic RNA3 to genomic RNA1 production, a key feature in the FHV
      life cycle mediated by a long-distance base pairing within RNA1. Depletion of
      LSM1, PAT1, or DHH1 dramatically increased RNA3 accumulation during replication.
      This was not caused by differences between RNA1 and RNA3 steady-state levels in
      the absence of replication. Importantly, coimmunoprecipitation assays indicated
      that LSm1-7, Pat1, and Dhh1 interact with the FHV RNA genome and the viral
      polymerase. By using a strategy that allows dissecting different stages of the
      replication process, we found that LSm1-7, Pat1, and Dhh1 did not affect the
      early replication steps of RNA1 recruitment to the replication complex or RNA1
      synthesis. Furthermore, their function on RNA3/RNA1 ratios was independent of the
      membrane compartment, where replication occurs and requires ATPase activity of
      the Dhh1 helicase. Together, these results support that LSm1-7, Pat1, and Dhh1
      control RNA3 synthesis. Their described function in mediating cellular mRNP
      rearrangements suggests a parallel role in mediating key viral RNP transitions,
      such as the one required to maintain the balance between the alternative FHV RNA1
      conformations that control RNA3 synthesis.

PMID- 23536654
TI  - Lymphoid-tissue stromal cells coordinate innate defense to cytomegalovirus.
AB  - During mouse cytomegalovirus (MCMV) infection, the first wave of type I
      interferon (IFN-I) production peaks at ~ 8 h. This IFN-I emanates from splenic
      stromal cells located in the marginal zone (MZ) and requires B cells that express
      lymphotoxin. The amount of IFN-I produced at these initial times is at least
      equivalent in magnitude to that produced later by dendritic cells (~ 36 to 48 h),
      but the relative roles of these two IFN-I sources in regulating MCMV defense
      remain unclear. Here we show that IFN-I produced by MZ stromal cells dramatically
      restricts the first measurable burst of viral production, which occurs at ~ 32 h.
      This primary innate control by IFN-I is partially mediated through the activation
      of natural killer (NK) cells, which produce gamma interferon in an IFN-I
      dependent fashion, and is independent of Ly49H. Strikingly, MCMV production in
      the spleens of immunocompetent mice never increases at times after 32 h. These
      results highlight the critical importance of lymphoid-tissue stromal cells in
      orchestrating the earliest phase of innate defense to MCMV infection, capping
      replication levels, and blocking spread until infection is ultimately controlled.

PMID- 23536655
TI  - Epstein-Barr virus negativity among individuals older than 60 years is associated
      with HLA-C and HLA-Bw4 variants and tonsillectomy.
AB  - Epstein-Barr virus (EBV) infects ~ 95% of the adult population. The factors that
      confer protection in the remaining ~ 5% remain unknown. In an exploratory study,
      we assessed immunogenetic factors and tonsillectomy in a cohort of 17 EBV
      negative and 39 EBV-positive healthy individuals aged >60 years. Analyses of HLA
      genotypes revealed an association between EBV negativity and the presence of HLA
      C-35T/T and/or HLA-Bw4 alleles. In addition, EBV-negative donors presented with a
      history of tonsillectomy more often than EBV-positive donors.

PMID- 23536656
TI  - Role of E1B55K in E4orf6/E1B55K E3 ligase complexes formed by different human
      adenovirus serotypes.
AB  - The E4orf6 protein of serotypes representing all human adenovirus species forms
      Cullin-based E3 ubiquitin ligase complexes that facilitate virus infection by
      inducing degradation of cellular proteins that impede efficient viral
      replication. This complex also includes the viral E1B55K product believed to bind
      and introduce substrates for ubiquitination. Heterogeneity in the composition of
      these ligases exists, as some serotypes form Cul5-based complexes whereas others
      utilize Cul2. Significant variations in substrate specificities also exist among
      serotypes, as some degrade certain substrates very efficiently whereas others
      induce more modest or little degradation. As E1B55K is believed to function as
      the substrate acquisition component of the ligase, we undertook studies to
      compare the ability of representative E1B55K proteins to bind substrates with the
      efficacy of degradation by their respective E4orf6-based ligases. Interestingly,
      although efficient degradation in some cases corresponded to the ability of
      E1B55K to bind to or relocalize substrates, there were several examples of
      substrates that bound efficiently to E1B55K but were not degraded and others in
      which substrates were degraded even though binding to E1B55K was low or
      undetectable. These results suggest that transient interactions with E1B55K may
      be sufficient for efficient substrate degradation and that binding alone is not
      sufficient, implying that the orientation of the substrate in the ligase complex
      is probably crucial. Nevertheless, we found that the substrate specificity of
      certain E4orf6-based ligases could be altered through the formation of hybrid
      complexes containing E1B55K from another serotype, thus confirming identification
      of E1B55K as the substrate acquisition component of the complex.

PMID- 23536657
TI  - Differentiation of human fetal multipotential neural progenitor cells to
      astrocytes reveals susceptibility factors for JC virus.
AB  - Viral infections of the central nervous system (CNS) are of increasing concern,
      especially among immunocompromised populations. Rodent models are often
      inappropriate for studies of CNS infection, as many viruses, including JC virus
      (JCV) and HIV, cannot replicate in rodent cells. Consequently, human fetal brain
      derived multipotential CNS progenitor cells (NPCs) that can be differentiated
      into neurons, oligodendrocytes, or astrocytes have served as a model in CNS
      studies. NPCs can be nonproductively infected by JCV, while infection of
      progenitor-derived astrocytes (PDAs) is robust. We profiled cellular gene
      expression at multiple times during differentiation of NPCs to PDAs. Several
      activated transcription factors show commonality between cells of the brain, in
      which JCV replicates, and lymphocytes, in which JCV is likely latent.
      Bioinformatic analysis determined transcription factors that may influence the
      favorable transcriptional environment for JCV in PDAs. This study attempts to
      provide a framework for understanding the functional transcriptional profile
      necessary for productive JCV infection.

PMID- 23536658
TI  - Qualitative and quantitative analysis of adenovirus type 5 vector-induced memory
      CD8 T cells: not as bad as their reputation.
AB  - It has been reported that adenovirus (Ad)-primed CD8 T cells may display a
      distinct and partially exhausted phenotype. Given the practical implications of
      this claim, we decided to analyze in detail the quality of Ad-primed CD8 T cells
      by directly comparing these cells to CD8 T cells induced through infection with
      lymphocytic choriomeningitis virus (LCMV). We found that localized immunization
      with intermediate doses of Ad vector induces a moderate number of functional CD8
      T cells which qualitatively match those found in LCMV-infected mice. The numbers
      of these cells may be efficiently increased by additional adenoviral boosting,
      and, importantly, the generated secondary memory cells cannot be qualitatively
      differentiated from those induced by primary infection with replicating virus.
      Quantitatively, DNA priming prior to Ad vaccination led to even higher numbers of
      memory cells. In this case, the vaccination led to the generation of a population
      of memory cells characterized by relatively low CD27 expression and high CD127
      and killer cell lectin-like receptor subfamily G member 1 (KLRG1) expression.
      These memory CD8 T cells were capable of proliferating in response to viral
      challenge and protecting against infection with live virus. Furthermore, viral
      challenge was followed by sustained expansion of the memory CD8 T-cell
      population, and the generated memory cells did not appear to have been driven
      toward exhaustive differentiation. Based on these findings, we suggest that
      adenovirus-based prime-boost regimens (including Ad serotype 5 [Ad5] and Ad5-like
      vectors) represent an effective means to induce a substantially expanded, long
      lived population of high-quality transgene-specific memory CD8 T cells.

PMID- 23536659
TI  - Guanine-nucleotide exchange factor RCC1 facilitates a tight binding between the
      encephalomyocarditis virus leader and cellular Ran GTPase.
AB  - The leader (L) protein of encephalomyocarditis virus (EMCV) shuts off host cell
      nucleocytoplasmic trafficking (NCT) by inducing hyperphosphorylation of nuclear
      pore proteins. This dramatic effect by a nonenzymatic protein of 6 kDa is not
      well understood but clearly involves L binding to cellular Ran GTPase, a critical
      factor of active NCT. Exogenous GDP and GTP are inhibitory to L-Ran binding, but
      the guanine-nucleotide exchange factor RCC1 can relieve this inhibition. In the
      presence of RCC1, L binds Ran with a KD (equilibrium dissociation constant) of ~
      3 nM and reaches saturation within 20 min. The results of fluorescently tagged
      nucleotide experiments suggest that L-Ran interactions affect the nucleotide
      binding pocket of Ran.

PMID- 23536660
TI  - Tyrosine 132 phosphorylation of influenza A virus M1 protein is crucial for virus
      replication by controlling the nuclear import of M1.
AB  - Phosphorylation of viral proteins plays important roles in the influenza A virus
      (IAV) life cycle. By using mass spectrometry, we identified tyrosine 132 (Y132)
      as a phosphorylation site of the matrix protein (M1) of the influenza virus
      A/WSN/1933(H1N1). Phosphorylation at this site is essential to the process of
      virus replication by controlling the nuclear import of M1. We further
      demonstrated that the phosphorylated tyrosine is crucial for the binding of M1 to
      the nuclear import factor importin-alpha1, since any substitutions at this site
      severely reduce this protein-protein interaction and damage the importin-alpha1
      mediated nuclear import of M1. Additionally, the tyrosine phosphorylation which
      leads to the nuclear import of M1 is blocked by a Janus kinase inhibitor. The
      present study reveals a pivotal role of this tyrosine phosphorylation in the
      intracellular transportation of M1, which controls the process of viral
      replication.

PMID- 23536661
TI  - Identification and characterization of genetically divergent members of the newly
      established family Mesoniviridae.
AB  - The recently established family Mesoniviridae (order Nidovirales) contains a
      single species represented by two closely related viruses, Cavally virus (CavV)
      and Nam Dinh virus (NDiV), which were isolated from mosquitoes collected in Cote
      d'Ivoire and Vietnam, respectively. They represent the first nidoviruses to be
      discovered in insects. Here, we report the molecular characterization of four
      novel mesoniviruses, Hana virus, Meno virus, Nse virus, and Moumo virus, all of
      which were identified in a geographical region in Cote d'Ivoire with high CavV
      prevalence. The viruses were found with prevalences between 0.5 and 2.8%, and
      genome sequence analyses and phylogenetic studies suggest that they represent at
      least three novel species. Electron microscopy revealed prominent club-shaped
      surface projections protruding from spherical, enveloped virions of about 120 nm.
      Northern blot data show that the four mesoniviruses analyzed in this study
      produce two major 3'-coterminal subgenomic mRNAs containing two types of 5'
      leader sequences resulting from the use of different pairs of leader and body
      transcription-regulating sequences that are conserved among mesoniviruses.
      Protein sequencing, mass spectroscopy, and Western blot data show that
      mesonivirus particles contain eight major structural protein species, including
      the putative nucleocapsid protein (25 kDa), differentially glycosylated forms of
      the putative membrane protein (20, 19, 18, and 17 kDa), and the putative spike
      (S) protein (77 kDa), which is proteolytically cleaved at a conserved site to
      produce S protein subunits of 23 and 57 kDa. The data provide fundamental new
      insight into common and distinguishing biological properties of members of this
      newly identified virus family.

PMID- 23536662
TI  - Generation of genetically stable recombinant rotaviruses containing novel genome
      rearrangements and heterologous sequences by reverse genetics.
AB  - The rotavirus (RV) genome consists of 11 segments of double-stranded RNA (dsRNA).
      Typically, each segment contains 5' and 3' untranslated regions (UTRs) that flank
      an open reading frame (ORF) encoding a single protein. RV variants with segments
      of atypical size owing to sequence rearrangements have been described. In many
      cases, the rearrangement originates from a partial head-to-tail sequence
      duplication that initiates after the stop codon of the ORF, leaving the protein
      product of the segment unaffected. To probe the limits of the RV genome to
      accommodate additional genetic sequence, we used reverse genetics to insert
      duplications (analogous to synthetic rearrangements) and heterologous sequences
      into the 3' UTR of the segment encoding NSP2 (gene 8). The approach allowed the
      recovery of recombinant RVs that contained sequence duplications (up to 200 bp)
      and heterologous sequences, including those for FLAG, the hepatitis C virus E2
      epitope, and the internal ribosome entry site of cricket paralysis virus. The
      recombinant RVs grew to high titer (>10(7) PFU/ml) and remained genetically
      stable during serial passage. Despite their longer 3' UTRs, rearranged RNAs of
      recombinant RVs expressed wild-type levels of protein in vivo. Competitive growth
      experiments indicated that, unlike RV segments with naturally occurring sequence
      duplications, genetically engineered segments were less efficiently packaged into
      progeny viruses. Thus, features of naturally occurring rearranged segments, other
      than their increased length, contribute to their enhanced packaging phenotype.
      Our results define strategies for developing recombinant RVs as expression
      vectors, potentially leading to next-generation RV vaccines that induce
      protection against other infectious agents.

PMID- 23536663
TI  - Substitutions T200A and E227A in the hemagglutinin of pandemic 2009 influenza A
      virus increase lethality but decrease transmission.
AB  - We report that swine influenza virus-like substitutions T200A and E227A in the
      hemagglutinin (HA) of the 2009 pandemic influenza virus alter its pathogenesis
      and transmission. Viral replication is increased in mammalian cells. Infected
      mice show increased disease as measured by weight loss and lethality.
      Transmission in ferrets is decreased in the presence of both substitutions,
      suggesting that amino acids 200T and 227E are adaptive changes in the HA of swine
      origin influenza viruses associated with increased transmission and decreased
      pathogenesis.

PMID- 23536664
TI  - The receptor attachment function of measles virus hemagglutinin can be replaced
      with an autonomous protein that binds Her2/neu while maintaining its fusion
      helper function.
AB  - Cell entry of enveloped viruses is initiated by attachment to the virus receptor
      followed by fusion between the virus and host cell membranes. Measles virus (MV)
      attachment to its receptor is mediated by the hemagglutinin (H), which is thought
      to produce conformational changes in the membrane fusion protein (F) that trigger
      insertion of its fusion peptide into the target cell membrane. Here, we uncoupled
      receptor attachment and the fusion-helper function of H by introducing Y481A,
      R533A, S548L, and F549S mutations into the viral attachment protein that made it
      blind to its normal receptors. An artificial receptor attachment protein specific
      for Her2/neu was incorporated into the membranes of pseudotyped lentivirus
      particles as a separate transmembrane protein along with the F protein.
      Surprisingly, these particles entered efficiently into Her2/neu-positive SK-OV-3
      as well as CHO-Her2 cells. Cell entry was independent of endocytosis but strictly
      dependent on the presence of H. H-specific monoclonal antibodies, as well as a
      mutation in H interfering with H/F cooperation, blocked cell entry. The particles
      mediated stable and specific transfer of reporter genes into Her2/neu-positive
      human tumor cells also in vivo, while exhibiting improved infectivity and higher
      titers than Her2/neu-targeted vectors displaying the targeting domain on H.
      Extending the current model of MV cell entry, the data suggest that receptor
      binding of H is not required for its fusion-helper function but that particle
      cell contact in general may be sufficient to induce the conformational changes in
      the H/F complex and activate membrane fusion.

PMID- 23536665
TI  - Recombination within the pandemic norovirus GII.4 lineage.
AB  - Norovirus (NoV) is the leading cause of viral gastroenteritis globally. Since
      1996, NoV variants of a single genetic lineage, GII.4, have been associated with
      at least six pandemics of acute gastroenteritis and caused between 62 and 80% of
      all NoV outbreaks. The emergence of these novel GII.4 variants has been
      attributed to rapid evolution and antigenic variation in response to herd
      immunity; however, the contribution of recombination as a mechanism facilitating
      emergence is increasingly evident. In this study, we sought to examine the role
      that intragenotype recombination has played in the emergence of GII.4 variants.
      Using a genome-wide approach including 25 complete genome sequences generated as
      part of this study, 11 breakpoints were identified within the NoV GII.4 lineage.
      The breakpoints were located at three recombination hot spots: near the open
      reading frame 1/2 (ORF1/2) and ORF2/3 overlaps, as well as within ORF2, which
      encodes the viral capsid, at the junction of the shell and protruding domains.
      Importantly, we show that recombination contributed to the emergence of the
      recent pandemic GII.4 variant, New Orleans 2009, and a newly identified GII.4
      variant, termed Sydney 2012. Reconstructing the evolutionary history of the GII.4
      lineage reveals the widespread impact of both inter- and intragenotype
      recombination on the emergence of many GII.4 variants. Lastly, this study
      highlights the many challenges in the identification of true recombination events
      and proposes that guidelines be applied for identifying NoV recombinants.

PMID- 23536667
TI  - Structure-function analysis of severe acute respiratory syndrome coronavirus RNA
      cap guanine-N7-methyltransferase.
AB  - Coronaviruses possess a cap structure at the 5' ends of viral genomic RNA and
      subgenomic RNAs, which is generated through consecutive methylations by virally
      encoded guanine-N7-methyltransferase (N7-MTase) and 2'-O-methyltransferase (2'-O
      MTase). The coronaviral N7-MTase is unique for its physical linkage with an
      exoribonuclease (ExoN) harbored in nonstructural protein 14 (nsp14) of
      coronaviruses. In this study, the structure-function relationships of the N7
      MTase were analyzed by deletion and site-directed mutagenesis of severe acute
      respiratory syndrome coronavirus (SARS-CoV) nsp14. The results showed that the
      ExoN domain is closely involved in the activity of the N7-MTase, suggesting that
      coronavirus N7-MTase is different from all other viral N7-MTases, which are
      separable from other structural domains located in the same polypeptide. Two of
      the 12 critical residues identified to be essential for the N7-MTase were located
      at the N terminus of the core ExoN domain, reinforcing a role of the ExoN domain
      in the N7-MTase activity of nsp14. The other 10 critical residues were
      distributed throughout the N7-MTase domain but localized mainly in the S-adenosyl
      l-methionine (SAM)-binding pocket and key structural elements of the MTase fold
      of nsp14. The sequence motif DxGxPxA (amino acids [aa] 331 to 338) was identified
      as the key part of the SAM-binding site. These results provide insights into the
      structure and functional mechanisms of coronaviral nsp14 N7-MTase.

PMID- 23536666
TI  - CD4+ T cells develop antiretroviral cytotoxic activity in the absence of
      regulatory T cells and CD8+ T cells.
AB  - Conventional CD4(+) T cells play an important role in viral immunity. In most
      virus infections, they provide essential help for antiviral B and T cell
      responses. In chronic infections, including HIV infection, an expansion of
      regulatory T cells (Tregs) has been demonstrated, which can suppress virus
      specific CD4(+) T cell responses in vitro. However, the suppressive activity of
      Tregs on effector CD4(+) T cells in retroviral infection is less well documented
      in vivo. We took advantage of a transgenic mouse in which Tregs can be
      selectively depleted to determine the influence of such cells on retrovirus
      specific CD4(+) T cell responses during an ongoing infection. Mice were infected
      with Friend retrovirus (FV), and Tregs were depleted during the acute phase of
      the infection. In nondepleted mice, activated CD4(+) T cells produced Th1-type
      cytokines but did not exhibit any antiviral cytotoxicity as determined in a major
      histocompatibility complex (MHC) class II-restricted in vivo cytotoxic T
      lymphocyte (CTL) assay. Depletion of Tregs significantly increased the numbers of
      virus-specific CD4(+) T cells and improved their cytokine production, whereas it
      induced only very little CD4(+) T cell cytotoxicity. However, after dual
      depletion of Tregs and CD8(+) T cells, conventional CD4(+) T cells developed
      significant cytotoxic activity against FV epitope-labeled target cells in vivo
      and contributed to the control of virus replication. Thus, both Tregs and CD8(+)
      T cells influence the cytotoxic activity of conventional CD4(+) T cells during an
      acute retroviral infection.

PMID- 23536668
TI  - MDA5 localizes to stress granules, but this localization is not required for the
      induction of type I interferon.
AB  - Virus infection can initiate a type I interferon (IFN-alpha/beta) response via
      activation of the cytosolic RNA sensors retinoic acid-inducible gene-I (RIG-I)
      and melanoma differentiation-associated gene 5 (MDA5). Furthermore, it can
      activate kinases that phosphorylate eukaryotic translation initiation factor
      2alpha (eIF2alpha), which leads to inhibition of (viral) protein translation and
      formation of stress granules (SG). Most viruses have evolved mechanisms to
      suppress these cellular responses. Here, we show that a mutant mengovirus
      expressing an inactive leader (L) protein, which we have previously shown to be
      unable to suppress IFN-alpha/beta, triggered SG formation in a protein kinase R
      (PKR)-dependent manner. Furthermore, we show that infection of cells that are
      defective in SG formation yielded higher viral RNA levels, suggesting that SG
      formation acts as an antiviral defense mechanism. Since the induction of both IFN
      alpha/beta and SG is suppressed by mengovirus L, we set out to investigate a
      potential link between these pathways. We observed that MDA5, the intracellular
      RNA sensor that recognizes picornaviruses, localized to SG. However, activation
      of the MDA5 signaling pathway did not trigger and was not required for SG
      formation. Moreover, cells that were unable to form SG-by protein kinase R (PKR)
      depletion, using cells expressing a nonphosphorylatable eIF2alpha protein, or by
      drug treatment that inhibits SG formation-displayed a normal IFN-alpha/beta
      response. Thus, although MDA5 localizes to SG, this localization seems to be
      dispensable for induction of the IFN-alpha/beta pathway.

PMID- 23536669
TI  - Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA
      targets and reveals phenotypic effects in culture.
AB  - Herpes simplex virus 1 (HSV-1), a ubiquitous human pathogen, expresses several
      viral microRNAs (miRNAs). These, along with the latency-associated transcript,
      represent the only viral RNAs detectable in latently infected neuronal cells.
      Here, for the first time, we analyze which HSV-1 miRNAs are loaded into the RNA
      induced silencing complex (RISC), the key effector of miRNA function. Only 9 of
      the 17 reported HSV-1 miRNAs, i.e., miR-H1 to miR-H8 plus miR-H11, were found to
      actually load into the RISC. Surprisingly, this analysis also revealed that HSV-1
      miRNAs loaded into the RISC with efficiencies that differed widely; <1% of the
      miR-H1-3p miRNA detectable in HSV-1-infected cells was loaded into the RISC.
      Analysis of HSV-1 mutants individually lacking the viral miR-H2, miR-H3, or miR
      H4 miRNA revealed that loss of these miRNAs affected the rate of replication of
      HSV-1 in neuronal cells but not in fibroblasts. Analysis of mRNA and protein
      expression, as well as assays mapping viral miRNA binding sites in infected
      cells, showed that endogenous HSV-1 miR-H2 binds to viral ICP0 mRNA and inhibits
      its expression, while endogenous miR-H4 inhibits the expression of the viral
      ICP34.5 gene. In contrast, no viral mRNA target for miR-H3 could be detected,
      even though miR-H3, like miR-H4, is perfectly complementary to ICP34.5 mRNA.
      Together, these data demonstrate that endogenous HSV-1 miRNA expression can
      significantly alter viral replication in culture, and they also identify two
      viral mRNA targets for miR-H2 and miR-H4 that can partially explain this
      phenotype.

PMID- 23536670
TI  - Griffithsin protects mice from genital herpes by preventing cell-to-cell spread.
AB  - Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the
      most potent HIV-1 inhibitory activity described for any antiviral lectin and is
      being developed for topical preexposure prophylaxis. The current studies were
      designed to further assess its potential by exploring its activity against herpes
      simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine
      model. Safety was evaluated by examining its impact on epithelial barrier
      integrity in polarized cultures and testing whether repeated intravaginal dosing
      potentiates the susceptibility of mice to genital herpes. Griffithsin displayed
      modest inhibitory activity against HSV-2 if present during viral entry but
      completely blocked plaque formation if present postentry, reduced plaque size,
      and prevented cell-to-cell spread. These in vitro findings translated to
      significant protection against genital herpes in mice treated with 0.1%
      griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread
      (visualized with a luciferase-expressing virus), significantly reduced disease
      scores, and resulted in greater survival (P < 0.05, log rank test). Protection
      persisted when HSV-2 was introduced in seminal plasma. Although griffithsin
      triggered a small decline in transepithelial electrical resistance in polarized
      cultures, this did not translate to any significant increase in the ability of
      HIV to migrate from the apical to the basolateral chamber nor to an increase in
      susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These
      findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of
      blocking cell-to-cell spread and support its further development for HIV and HSV
      2 prevention.

PMID- 23536671
TI  - Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2
      from endothelial cells.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation,
      angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which
      involves various growth factors and cytokines. Previously, we found that KSHV
      infection of human umbilical vein endothelial cells (HUVECs) induces a
      transcriptional induction of the proangiogenic and proinflammatory cytokine
      angiopoietin-2 (Ang-2). Here, we report that KSHV induces rapid release of Ang-2
      that is presynthesized and stored in the Weibel-Palade bodies (WPB) of
      endothelial cells upon binding to its integrin receptors. Blocking viral binding
      to integrins inhibits Ang-2 release. KSHV binding activates the integrin tyrosine
      kinase receptor signaling pathways, leading to tyrosine phosphorylation of focal
      adhesion kinase (FAK), the tyrosine kinase Src, and the Calalpha2 subunit of the
      l-type calcium channel to trigger rapid calcium (Ca(2+)) influx. Pretreatment of
      endothelial cells with specific inhibitors of protein tyrosine kinases inhibits
      KSHV-induced Ca(2+) influx and Ang-2 release. Inhibition of Ca(2+) mobilization
      with calcium channel blockers also inhibits Ang-2 release. Thus, the interaction
      between KSHV and its integrin receptors plays a key role in regulating rapid Ang
      2 release from endothelial cells. This finding highlights a novel mechanism of
      viral induction of angiogenesis and inflammation, which might play important
      roles in the early event of KS tumor development.

PMID- 23536672
TI  - A novel PCR assay for quantification of HIV-1 RNA.
AB  - Current assays for quantification of HIV-1 virions rely on real-time reverse
      transcriptase (RT)-PCR detection of conserved regions of HIV-1 RNA and can be
      limited by detection of contaminating viral or plasmid DNA. We developed a novel
      RT-PCR assay using a reverse primer that hybridizes with the poly(A) tail of HIV
      1 mRNAs, anchored by conserved viral nucleotides at the most distal region of the
      transcript. This assay can detect and quantify HIV-1 RNA with high specificity
      and sensitivity.

PMID- 23536673
TI  - Human cytomegalovirus induces a biphasic inflammatory response in primary
      endothelial cells.
AB  - Contradictory studies report either pro- or anti-inflammatory endothelial cell
      (EC) responses to human cytomegalovirus (hCMV) infection, hindering the
      validation of a potential link between this virus and associated inflammatory
      pathologies. Clarifying this issue, we report that hCMV induces a biphasic
      response. Early after inoculation, hCMV promoted lymphocyte and, to a lesser
      extent, neutrophil capture under in vivo relevant shear stresses. In contrast,
      later stages of infection rendered EC refractory to basal, or cytokine-induced,
      leukocyte recruitment.

PMID- 23536674
TI  - The ULb' region of the human cytomegalovirus genome confers an increased
      requirement for the viral protein kinase UL97.
AB  - We report a requirement for the viral protein kinase UL97 in human
      cytomegalovirus (HCMV) replication that maps to the ULb' region of the viral
      genome. A UL97-null (Delta97) mutant of strain TB40/E, which encodes a full
      length ULb' region, exhibited replication defects, particularly in production of
      cell-free virus, that were more severe than those seen with a Delta97 mutant of
      laboratory strain AD169, which harbors extensive deletions in its ULb' region.
      These differences were recapitulated with additional HCMV strains by treatment
      with a UL97 kinase inhibitor, 1-(beta-L-ribofuranosyl)-2-isopropylamino-5,6
      dichlorobenzimidazole (maribavir). We observed lower levels of viral DNA
      synthesis and an increased requirement for UL97 in viral late gene expression in
      strains with full-length ULb' regions. Analysis of UL97-deficient TB40/E
      infections by electron microscopy revealed fewer C-capsids in nuclei, unusual
      viral particles in the cytoplasmic assembly compartment, and defective viral
      nuclear egress. Partial inhibition of viral DNA synthesis caused defects in
      production of cell-free virus that were up to ~ 100-fold greater than those seen
      with cell-associated virus in strains TB40/E and TR, suggesting that UL97
      dependent defects in cell-free virus production in strains with full-length ULb'
      regions were secondary to DNA synthesis defects. Accordingly, a chimeric virus in
      which the ULb' region of TB40/E was replaced with that of AD169 showed reduced
      effects of UL97 inhibition on viral DNA synthesis, late gene expression, and
      production of cell-free virus compared to parental TB40/E. Together, these
      results argue that the ULb' region encodes a factor(s) which invokes an increased
      requirement for UL97 during viral DNA synthesis.

PMID- 23536675
TI  - Rift Valley fever virus clearance and protection from neurologic disease are
      dependent on CD4+ T cell and virus-specific antibody responses.
AB  - Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and
      livestock throughout Africa and the Arabian Peninsula. Human RVFV infections
      generally manifest as a self-limiting febrile illness, but in some individuals,
      the disease can progress to a fatal encephalitis or hemorrhagic syndrome. Little
      is known about the host characteristics that predispose development of more
      severe disease. Early in infection, interferon-mediated antiviral responses are
      critical for controlling RVFV replication, but the roles of downstream adaptive
      immune responses in determining clinical outcome have not been examined. Here,
      using a C57BL/6 mouse disease model, we evaluated the roles of B cells and T
      cells in RVFV pathogenesis. Given the profound inhibition of the innate response
      by the viral NSs protein and rapid course of wild-type infection, we utilized an
      attenuated RVFV lacking NSs to examine host responses following primary
      infection. Experiments utilizing B-cell-deficient mice or targeted T cell
      depletions of wild-type mice demonstrated that B cells and CD4(+) T cells, but
      not CD8(+) T cells, were critical for mediating viral clearance, even in the
      presence of a functional innate response. One-third of CD4-depleted mice
      developed severe neurologic disease following infection, in contrast to virus
      infected mock-depleted mice that showed no clinical signs. CD4(+) T cells were
      required for robust IgG and neutralizing antibody responses that correlated with
      RVFV clearance from peripheral tissues. Furthermore, CD4-depleted mice
      demonstrated significantly stronger proinflammatory responses relative to
      controls, suggesting CD4(+) T cells regulate immune responses to RVFV infection.
      Together, these results indicate CD4(+) T cells are critical determinants of RVFV
      pathogenesis and play an important role in preventing onset of neurologic
      disease.

PMID- 23536676
TI  - Sigma-1 receptor regulates early steps of viral RNA replication at the onset of
      hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) genome replication is thought to occur in a membranous
      cellular compartment derived from the endoplasmic reticulum (ER). The molecular
      mechanisms by which these membrane-associated replication complexes are formed
      during HCV infection are only starting to be unraveled, and both viral and
      cellular factors contribute to their formation. In this study, we describe the
      discovery of nonopioid sigma-1 receptor (S1R) as a cellular factor that mediates
      the early steps of viral RNA replication. S1R is a cholesterol-binding protein
      that resides in lipid-rich areas of the ER and in mitochondrion-associated ER
      membranes (MAMs). Several functions have been ascribed to this ER-resident
      chaperone, many of which are related to Ca(2+) signaling at the MAMs and lipid
      storage and trafficking. Downregulation of S1R expression by RNA interference
      (RNAi) in Huh-7 cells leads to a proportional decrease in susceptibility to HCV
      infection, as shown by reduced HCV RNA accumulation and intra- and extracellular
      infectivity in single-cycle infection experiments. Similar RNAi studies in
      persistently infected cells indicate that S1R expression is not rate limiting for
      persistent HCV RNA replication, as marked reduction in S1R in these cells does
      not lead to any decrease in HCV RNA or viral protein expression. However,
      subgenomic replicon transfection experiments indicate that S1R expression is rate
      limiting for HCV RNA replication without impairing primary translation. Overall,
      our data indicate that the initial steps of HCV infection are regulated by S1R, a
      key component of MAMs, suggesting that these structures could serve as platforms
      for initial RNA replication during HCV infection.

PMID- 23536677
TI  - Rotavirus prevents the expression of host responses by blocking the
      nucleocytoplasmic transport of polyadenylated mRNAs.
AB  - Rotaviruses are the most important agent of severe gastroenteritis in young
      children. Early in infection, these viruses take over the host translation
      machinery, causing a severe shutoff of cell protein synthesis while viral
      proteins are efficiently synthesized. In infected cells, there is an accumulation
      of the cytoplasmic poly(A)-binding protein in the nucleus, induced by the viral
      protein NSP3. Here we found that poly(A)-containing mRNAs also accumulate and
      become hyperadenylated in the nuclei of infected cells. Using reporter genes
      bearing the untranslated regions (UTRs) of cellular or viral genes, we found that
      the viral UTRs do not determine the efficiency of translation of mRNAs in
      rotavirus-infected cells. Furthermore, we showed that while a polyadenylated
      reporter mRNA directly delivered into the cytoplasm of infected cells was
      efficiently translated, the same reporter introduced as a plasmid that needs to
      be transcribed and exported to the cytoplasm was poorly translated. Altogether,
      these results suggest that nuclear retention of poly(A)-containing mRNAs is one
      of the main strategies of rotavirus to control cell translation and therefore the
      host antiviral and stress responses.

PMID- 23536678
TI  - The tobamovirus Turnip Vein Clearing Virus 30-kilodalton movement protein
      localizes to novel nuclear filaments to enhance virus infection.
AB  - Plant viruses overcome the barrier of the plant cell wall by encoding cell-to
      cell movement proteins (MPs), which direct newly replicated viral genomes to, and
      across, the wall. The paradigm for how a single MP regulates and coordinates
      these activities is the Tobacco mosaic virus (TMV) 30-kDa protein (MP(TMV)).
      Detailed studies demonstrate that TMV multiplies exclusively in the cytoplasm and
      have documented associations of MP(TMV) with endoplasmic reticulum (ER) membrane,
      microtubules, and plasmodesmata throughout the course of infection. As TMV poorly
      infects Arabidopsis thaliana, Turnip vein clearing virus (TVCV) is the
      tobamovirus of choice for studies in this model plant. A key problem, which has
      contributed to confusion in the field, is the unproven assumption that the TVCV
      and TMV life cycles are identical. We engineered an infectious TVCV replicon that
      expressed a functional fluorescence-tagged MP(TVCV) and report here the
      unexpected discovery that MP(TVCV), beyond localizing to ER membrane and
      plasmodesmata, targeted to the nucleus in a nuclear localization signal (NLS)
      dependent manner, where it localized to novel F-actin-containing filaments that
      associated with chromatin. The MP(TVCV) NLS appeared to be conserved in the
      subgroup 3 tobamoviruses, and our mutational analyses showed that nuclear
      localization of MP(TVCV) was necessary for efficient TVCV cell-to-cell movement
      and systemic infection in Nicotiana benthamiana and Arabidopsis thaliana. Our
      studies identify a novel nuclear stage in TVCV infection and suggest that nuclear
      MP encoded by TVCV and other subgroup 3 tobamoviruses interacts with F-actin and
      chromatin to modulate host defenses or cellular physiology to favor virus
      movement and infection.

PMID- 23536679
TI  - T cells target APOBEC3 proteins in human immunodeficiency virus type 1-infected
      humans and simian immunodeficiency virus-infected Indian rhesus macaques.
AB  - APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the
      retroviral genome during reverse transcription. To counteract APOBEC3 and gain a
      replicative advantage, lentiviruses such as human immunodeficiency virus type 1
      (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein,
      which targets APOBEC3 proteins for proteasomal degradation. However, the
      proteasome plays a critical role in the generation of T cell peptide epitopes.
      Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and
      presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus
      infected cells remains unknown. Here, using peptides derived from multiple Vif
      sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in
      both HIV-1-infected patients and SIV-infected rhesus macaques. These results
      raise the possibility that these T cell responses may be part of the larger
      antiretroviral immune response.

PMID- 23536681
TI  - Differential recognition of Old World and New World arenavirus envelope
      glycoproteins by subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P).
AB  - The arenaviruses are an important family of emerging viruses that includes
      several causative agents of severe hemorrhagic fevers in humans that represent
      serious public health problems. A crucial step of the arenavirus life cycle is
      maturation of the envelope glycoprotein precursor (GPC) by the cellular
      subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). Comparison of the
      currently known sequences of arenavirus GPCs revealed the presence of a highly
      conserved aromatic residue at position P7 relative to the SKI-1/S1P cleavage side
      in Old World and clade C New World arenaviruses but not in New World viruses of
      clades A and B or cellular substrates of SKI-1/S1P. Using a combination of
      molecular modeling and structure-function analysis, we found that residue Y285 of
      SKI-1/S1P, distal from the catalytic triad, is implicated in the molecular
      recognition of the aromatic "signature residue" at P7 in the GPC of Old World
      Lassa virus. Using a quantitative biochemical approach, we show that Y285 of SKI
      1/S1P is crucial for the efficient processing of peptides derived from Old World
      and clade C New World arenavirus GPCs but not of those from clade A and B New
      World arenavirus GPCs. The data suggest that during coevolution with their
      mammalian hosts, GPCs of Old World and clade C New World viruses expanded the
      molecular contacts with SKI-1/S1P beyond the classical four-amino-acid
      recognition sequences and currently occupy an extended binding pocket.

PMID- 23536682
TI  - Phylogenetic considerations in designing a broadly protective multimeric L2
      vaccine.
AB  - While the oncogenic human papillomavirus (HPV) types with the greatest medical
      impact are clustered within the alpha9 and alpha7 species, a significant fraction
      of cervical cancers are caused by alpha5, alpha6, and alpha11 viruses. Benign
      genital warts are caused principally by the alpha10 viruses HPV6 and HPV11. In an
      effort to achieve broad protection against both cervical cancer- and genital wart
      associated types, we produced at high levels in bacteria a multimeric protein
      (alpha11-88x8) fusing eight polypeptides corresponding to a protective domain
      comprising L2 residues ~11 to 88 derived from HPV6 (alpha10), HPV16 (alpha9),
      HPV18 (alpha7), HPV31 (alpha9), HPV39 (alpha7), HPV51 (alpha5), HPV56 (alpha6),
      and HPV73 (alpha11) and a truncated derivative with the last three units deleted
      (alpha11-88x5). Mice were immunized three times with alpha11-88x8 or alpha11-88x5
      adjuvanted with alum or the licensed HPV vaccines and challenged intravaginally
      with HPV6, HPV16, HPV26, HPV31, HPV33, HPV35, HPV45, HPV51, HPV56, HPV58, or
      HPV59 pseudovirions. The alpha11-88x5 and alpha11-88x8 vaccines induced similarly
      robust protection against each HPV type tested and indistinguishable HPV16
      neutralizing antibody titers. Passive transfer of alpha11-88x8 antisera was
      protective. Further, rabbit antisera to alpha11-88x8 and alpha11-88x5 similarly
      neutralized native HPV18 virions. These findings suggest that immunologic
      competition between units is not a significant issue and that it is not necessary
      to include a unit of L2 derived from each species to achieve broader protection
      against diverse medically significant HPV types than is achieved with the
      licensed HPV vaccines.

PMID- 23536680
TI  - HIV-1 Gag associates with specific uropod-directed microdomains in a manner
      dependent on its MA highly basic region.
AB  - In polarized T cells, HIV-1 Gag localizes to a rear-end protrusion known as the
      uropod in a multimerization-dependent manner. Gag-laden uropods participate in
      formation of virological synapses, intercellular contact structures that play a
      key role in cell-to-cell HIV-1 transmission. Our previous observations suggest
      that Gag associates with uropod-directed microdomains (UDMs) that eventually
      comigrate with Gag to the uropod over the cell surface. However, the nature of
      Gag multimerization required for this movement, the composition of the UDMs, and
      the molecular determinants for Gag association with these microdomains remain
      unknown. In this study, we found that Gag multimerization prior to budding but
      beyond dimerization is necessary for Gag localization to the uropods, indicating
      that uropod localization occurs early in the assembly process. We also found that
      prior to membrane curvature, Gag multimers associate with a specific subset of
      UDMs containing PSGL-1, CD43, and CD44 but not ICAM-1, ICAM-3, or CD59. Notably,
      upon association, Gag excludes ICAM-3 from this subset of UDMs, revealing an
      active and selective reorganization of these microdomains by Gag. This specific
      association between Gag and UDMs is dependent on the highly basic region (HBR) in
      the Gag matrix (MA) domain. The overall positive charge of the HBR was needed for
      the interaction with the specific UDM subset, while the exact HBR sequence was
      not, unlike that seen for MA binding to the plasma membrane phospholipid
      phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. Taken together, these
      findings revealed that HIV-1 Gag associates with specific microdomains present in
      polarized T cells in an MA-dependent manner, which results in modification of the
      microdomain constituents.

PMID- 23536683
TI  - Regulation of hepatitis B virus infection by Rab5, Rab7, and the endolysosomal
      compartment.
AB  - Despite important progress toward deciphering human hepatitis B virus (HBV) entry
      into host cells, many aspects of the early steps of the life cycle remained
      completely obscure. Following endocytosis, HBV must travel through the complex
      network of the endocytic pathway to reach the cell nucleus and initiate
      replication. In addition to guiding the viral particles to the replication site,
      the endosomal vesicles may play a crucial role in infection, providing the
      appropriate environment for virus uncoating and nucleocapsid release. In this
      work, we investigated the trafficking of HBV particles internalized in permissive
      cells. Expression of key Rab proteins, involved in specific pathways leading to
      different intracellular locations, was modulated in HepaRG cells, using a stable
      and inducible short hairpin RNA (shRNA) expression system. The trafficking
      properties of the newly developed cells were demonstrated by confocal microscopy
      and flow cytometry using specific markers. The results showed that HBV infection
      strongly depends on Rab5 and Rab7 expression, indicating that HBV transport from
      early to mature endosomes is required for a step in the viral life cycle. This
      may involve reduction of disulfide bond-linked envelope proteins, as alteration
      of the redox potential of the endocytic pathway resulted in inhibition of
      infection. Subcellular fractionation of HBV-infected cells showed that viral
      particles are further transported to lysosomes. Intriguingly, infection was not
      dependent on the lysosomal activity, suggesting that trafficking to this
      compartment is a "dead-end" route. Together, these data add to our understanding
      of the HBV-host cell interactions controlling the early stages of infection.

PMID- 23536684
TI  - The transcriptome of the baculovirus Autographa californica multiple
      nucleopolyhedrovirus in Trichoplusia ni cells.
AB  - Baculoviruses are important insect pathogens that have been developed as protein
      expression vectors in insect cells and as transduction vectors for mammalian
      cells. They have large double-stranded DNA genomes containing approximately 156
      tightly spaced genes, and they present significant challenges for transcriptome
      analysis. In this study, we report the first comprehensive analysis of AcMNPV
      transcription over the course of infection in Trichoplusia ni cells, by a
      combination of strand-specific RNA sequencing (RNA-Seq) and deep sequencing of 5'
      capped transcription start sites and 3' polyadenylation sites. We identified four
      clusters of genes associated with distinctive patterns of mRNA accumulation
      through the AcMNPV infection cycle. A total of 218 transcription start sites
      (TSS) and 120 polyadenylation sites (PAS) were mapped. Only 29 TSS were
      associated with a canonical TATA box, and 14 initiated within or near the
      previously identified CAGT initiator motif. The majority of viral transcripts
      (126) initiated within the baculovirus late promoter motif (TAAG), and late
      transcripts initiated precisely at the second position of the motif. Analysis of
      3' ends showed that 92 (77%) of the 3' PAS were located within 30 nucleotides
      (nt) downstream of a consensus termination signal (AAUAAA or AUUAAA). A conserved
      U-rich region was found approximately 2 to 10 nt downstream of the PAS for 58
      transcripts. Twelve splicing events and an unexpectedly large number of antisense
      RNAs were identified, revealing new details of possible regulatory mechanisms
      controlling AcMNPV gene expression. Combined, these data provide an emerging
      global picture of the organization and regulation of AcMNPV transcription through
      the infection cycle.

PMID- 23536687
TI  - Inheritance of autoinflammatory diseases: shifting paradigms and nomenclature.
AB  - Over 15 years have passed since the discovery of the first autoinflammatory gene,
      MEFV, responsible for familial Mediterranean fever. The identification of another
      gene, TNFRSF1A, in 1999 led to the concept of autoinflammation which
      characterises rheumatological conditions triggered by a defective innate
      immunity. Substantive progress has been made since then with the identification
      of 18 autoinflammatory genes accounting for up to 24 disease entities showing
      overlapping symptoms. The accumulation of studies reporting patients with missing
      or excess mutations as compared with expected numbers favours the hypothesis that
      these diseases are distributed along a continuum ranging from monogenic to
      multifactorial conditions, rather than featuring only classical modes of
      inheritance. Moreover, the probable interactions of environmental and epigenetic
      factors further obscure our understanding of the mechanisms underlying the
      phenotypic expression of patients. This review explores the history of
      autoinflammatory gene discovery, discusses the nosological disparities stemming
      from the clinical versus pathophysiological definition of autoinflammatory
      diseases and summarises various inheritance patterns. This review calls for a
      consistent disease nomenclature and presents a reconciling hypothesis which
      places different sequence variants within the autoinflammatory disease continuum.
      Integrating these new concepts should help to facilitate communication between
      health professionals and promote personalised patient care.

PMID- 23536686
TI  - A comparison of murine leukemia viruses that escape from human and rhesus macaque
      TRIM5alphas.
AB  - To better understand the binding mechanism of TRIM5alpha to retrovirus capsid, we
      had previously selected N-tropic murine leukemia virus (N-MLV) mutants escaping
      from rhesus macaque TRIM5alpha (rhTRIM5alpha) by passaging the virus in
      rhTRIM5alpha-expressing cells and selecting for nonrestricted variants. To test
      the commonality of the findings from the rhTRIM5alpha study, we have now employed
      a similar genetic approach using human TRIM5alpha (huTRIM5alpha). Consistent with
      the rhTRIM5alpha study, the mapped huTRIM5alpha escape mutations were distributed
      across the capsid exterior, confirming the extended binding surface between virus
      and restriction factor. Compared to the results of the previous study, fewer
      escape mutations were identified, with particular mutants being repeatedly
      selected. Three out four huTRIM5alpha escape variants showed resistance to all
      primate TRIM5alphas tested, but two of them sacrificed viral fitness,
      observations that were not made in the rhTRIM5alpha study. Moreover, differences
      in amino acid changes associated with escape from hu- and rhTRIM5alphas suggested
      a charge dependence of the restriction by different TRIM5alphas. Taken together,
      these results suggest that the recognition of the entire capsid surface is a
      general strategy for TRIM5alpha to restrict MLV but that significantly different
      specific interactions are involved in the binding of TRIM5alpha from different
      species to the MLV capsid core.

PMID- 23536685
TI  - The evolving field of human papillomavirus receptor research: a review of binding
      and entry.
AB  - Human papillomaviruses (HPVs) infect epithelia and can lead to the development of
      lesions, some of which have malignant potential. HPV type 16 (HPV16) is the most
      oncogenic genotype and causes various types of cancer, including cervical, anal,
      and head and neck cancers. However, despite significant research, our
      understanding of the mechanism by which HPV16 binds to and enters host cells
      remains fragmented. Over several decades, many HPV receptors and entry pathways
      have been described. This review puts those studies into context and offers a
      model of HPV16 binding and entry as a framework for future research. Our model
      suggests that HPV16 binds to heparin sulfate proteoglycans (HSPGs) on either the
      epithelial cell surface or basement membrane through interactions with the L1
      major capsid protein. Growth factor receptors may also become activated through
      HSPG/growth factor/HPV16 complexes that initiate signaling cascades during early
      virion-host cell interactions. After binding to HSPGs, the virion undergoes
      conformational changes, leading to isomerization by cyclophilin B and proprotein
      convertase-mediated L2 minor capsid protein cleavage that increases L2 N terminus
      exposure. Along with binding to HSPGs, HPV16 binds to alpha6 integrins, which
      initiate further intracellular signaling events. Following these primary binding
      events, HPV16 binds to a newly identified L2-specific receptor, the annexin A2
      heterotetramer. Subsequently, clathrin-, caveolin-, lipid raft-, flotillin-,
      cholesterol-, and dynamin-independent endocytosis of HPV16 occurs.

PMID- 23536688
TI  - Lay REC members: patient or public?
AB  - In practice, the role of lay members of research ethics committees (RECs) often
      involves checking the accessibility of written materials, checking that the
      practical needs of participants have been considered and ensuring that a lay
      summary of the research will be produced. In this brief report, I argue that all
      these tasks would be more effectively carried out through a process of patient
      involvement (PI) in research projects prior to ethical review. Involving patients
      with direct experience of the topic under investigation brings added value beyond
      the contributions typically made by lay REC members, who are often not patients
      themselves. This is because PI tailors the design and conduct of research to the
      specific interests and concerns of the people who will actually take part in a
      project and make use of its findings. If a project has PI in its early stages,
      then a similar input from lay REC members could at best result in duplication of
      effort and at worst create the potential for conflict. The rationale for lay REC
      membership will therefore need to change from 'contributing a patient
      perspective' to 'ensuring transparency and public accountability in REC
      decisions'. This has implications for addressing more strategic questions about
      lay REC membership, including who is best recruited to the role and how they
      should be expected to contribute in practice. 

PMID- 23536689
TI  - Surprisingly low seroprevalence of Burkholderia pseudomallei in exposed healthy
      adults in the Darwin region of tropical Australia where melioidosis is highly
      endemic.
AB  - In the Darwin region of Australia where melioidosis is highly endemic, only
      11/354 (3%) healthy residents were seropositive by indirect hemagglutination
      assay, despite extensive exposure to Burkholderia pseudomallei. None developed
      melioidosis, but some described a prior self-limiting illness. This
      seropositivity rate is much lower than that seen in northeast Thailand, where
      melioidosis is similarly highly endemic, potentially reflecting important
      differences between these two locations in the epidemiology of melioidosis.

PMID- 23536690
TI  - Combined administration of MF59-adjuvanted A/H5N1 prepandemic and seasonal
      influenza vaccines: long-term antibody persistence and robust booster responses 1
      year after a one-dose priming schedule.
AB  - Having previously demonstrated the feasibility of administering A/H5N1 and
      seasonal influenza vaccine antigens in an MF59-adjuvanted tetravalent
      formulation, we now report on long-term antibody persistence and responses to a
      booster dose of a combined seasonal-pandemic, tetravalent influenza vaccine in
      adults. The primary objective was the evaluation of responses to a booster dose
      of tetravalent influenza vaccine containing seasonal (A/H1N1, A/H3N2, and B) and
      avian (A/H5N1, clade 2) influenza virus strains administered to 265 healthy 18-
      to 40-year-old volunteers 1 year after priming with one or two clade 1 A/H5N1
      doses. Secondary objectives were assessment of reactogenicity, safety, and
      antibody persistence 1 year after priming with a combined seasonal-pandemic,
      tetravalent vaccine. Responses to seasonal strains met all European licensure
      criteria; seroprotection rates were 94 to 100%, 100%, and 61 to 90% for A/H1N1,
      A/H3N2, and B strains, respectively. Anamnestic responses were observed against
      homologous and heterologous A/H5N1 strains whether priming with one or two A/H5N1
      doses, with a monovalent A/H5N1 vaccine, or with a tetravalent vaccine. A single
      dose of MF59-adjuvanted A/H5N1 vaccine given alone or as part of a fixed
      combination with a seasonal influenza vaccine was sufficient to prime adult
      subjects, resulting in robust antigen-specific and cross-reactive antibody
      responses to heterologous booster immunization 1 year later. These data support
      the feasibility of incorporating prepandemic priming into seasonal influenza
      vaccination programs. (This study has been registered at clinicaltrials.gov under
      registration no. NCT00481065.).

PMID- 23536691
TI  - Protection of piglets by a Haemophilus parasuis ghost vaccine against homologous
      challenge.
AB  - Commercial bacterins for Glasser's disease are widely used for the prevention of
      this disease caused by Haemophilus parasuis; however, the protective efficacy
      varies depending on the strain and serovar. Bacterial ghosts (BGs) are empty
      bacterial envelopes that, unlike classic bacterins, suffer no denaturing steps
      during their production. These properties may lead to superior protection. In
      this study, a BG vaccine generated from the Haemophilus parasuis serovar 5
      reference strain Nagasaki was prepared and used to inoculate piglets. The
      efficacy of the BG vaccine was evaluated by clinical, bacteriological,
      serological, and postmortem examinations. Inactivated bacterin (IB) and a placebo
      control (PC) were compared with the BG vaccine in this study. The results showed
      that the piglets inoculated with the BG vaccine developed higher antibody
      activity and higher gamma interferon and interleukin 4 levels than those
      vaccinated with IB or those in the PC group after primary and secondary exposure
      to the antigens and challenge. CD4(+) T lymphocyte levels were observed to
      increase following secondary immunization more in the BG-vaccinated group than in
      the IB (P < 0.05) and PC (P < 0.05) groups. CD8(+) T lymphocyte levels increased
      dramatically in all three groups after challenge, and the differences between
      groups were all significant (P < 0.05). There were fewer tissue lesions and lower
      bacterial loads in the tissue homogenates in the BG group after challenge. The
      results suggest that higher CD4(+) T lymphocyte levels and both CD4(+) major
      histocompatibility complex class II-restricted Th1-type and Th2-type immune
      responses in the BG group are relevant for protection.

PMID- 23536692
TI  - Immunogenicity and safety of an inactivated trivalent split influenza virus
      vaccine in young children with recurrent wheezing.
AB  - Influenza virus vaccination is recommended for children, but so far, active
      vaccination has not been achieved because most parents lack knowledge of vaccine
      safety and many doctors are reluctant to administer vaccine due to concerns that
      steroids might alter immunogenicity. The aim of this study was to compare the
      immunogenicity and safety of inactivated trivalent split influenza virus vaccine
      between children with recurrent wheezing and healthy children of the same age
      group. Sixty-eight healthy children and 62 children with recurrent wheezing took
      part in this study. Seroconversion rates, seroprotection rates, geometric mean
      titers (GMTs), and geometric mean titer ratios (GMTRs) were measured by a
      hemagglutination inhibition assay for the assessment of immunogenicity. Solicited
      and unsolicited local and systemic adverse events were measured for the
      assessment of safety. Regarding immunogenicity, the seroconversion and
      seroprotection rates showed no difference overall between healthy children and
      children with recurrent wheezing. Also, no difference was observed between
      steroid-treated and nontreated groups with recurrent wheezing. Generally, the
      GMTs after vaccination were higher in the one-dose vaccination groups for healthy
      children and children with recurrent wheezing, but the GMTRs revealed different
      results according to strain in the two groups. Regarding safety, solicited local
      and systemic adverse events showed no differences between healthy children and
      children with recurrent wheezing. This study demonstrates that inactivated split
      influenza virus vaccine is able to induce protective immune responses in healthy
      children, as observed in previous studies, as well as in children with recurrent
      wheezing who require frequent steroid treatment.

PMID- 23536693
TI  - Mycoplasma fermentans MALP-2 induces heme oxygenase-1 expression via mitogen
      activated protein kinases and Nrf2 pathways to modulate cyclooxygenase 2
      expression in human monocytes.
AB  - Heme oxygenase-1 (HO-1) is a stress-inducible rate-limiting enzyme in heme
      degradation that confers cytoprotection against oxidative injury and performs a
      vital function in the maintenance of cell hemostasis. Increasing numbers of
      reports have indicated that mycoplasma-derived membrane
      lipoproteins/lipopeptides, such as macrophage-activating lipopeptide-2 (MALP-2),
      function as agents that stimulate the immune system by producing various
      inflammatory mediators, such as cytokines and cyclooxygenase 2 (COX-2), which
      play roles in the pathogenesis of inflammatory responses during mycoplasma
      infection. Here, we report that MALP-2 induced HO-1 mRNA and protein expression
      and upregulated HO-1 enzyme activity in THP-1 cells. Specific inhibitors of
      mitogen-activated protein kinases (MAPKs), SB203580, PD98059, and SP600125,
      significantly abolished HO-1 expression. In addition, MALP-2 also induced NF-E2
      related factor 2 (Nrf2) translocation, and the silencing of Nrf2 expression in
      THP-1 cells decreased the levels of MALP-2-mediated HO-1 expression. Furthermore,
      COX-2 protein expression levels were upregulated in THP-1 cells in response to
      MALP-2, and transfection with small interfering RNAs of HO-1 significantly
      increased COX-2 accumulation. These results demonstrate that MALP-2 induces HO-1
      expression via MAPKs and Nrf2 pathways and, furthermore, that MALP-2-induced COX
      2 expression was modulated by HO-1 in THP-1 cells.

PMID- 23536694
TI  - Transgenic parasites stably expressing full-length Plasmodium falciparum
      circumsporozoite protein as a model for vaccine down-selection in mice using
      sterile protection as an endpoint.
AB  - Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human
      malaria vaccine candidate. There is an urgent need for models that can rapidly
      down-select novel CSP-based vaccine candidates. In the present study, the mouse
      mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite
      stably expressing a functional full-length P. falciparum CSP was optimized to
      consistently produce infective sporozoites for protection studies. A minimal
      sporozoite challenge dose was established, and protection was defined as the
      absence of blood-stage parasites 14 days after intravenous challenge. The
      specificity of protection was confirmed by vaccinating mice with multiple CSP
      constructs of differing lengths and compositions. Constructs that induced high
      NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were
      protective, and the degree of protection was dependent on the antigen dose. There
      was a positive correlation between antibody avidity and protection. The
      antibodies in the protected mice recognized the native CSP on the parasites and
      showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP
      antibodies into naive mice also induced protection. Thus, we have demonstrated
      the utility of a mouse efficacy model to down-select human CSP-based vaccine
      formulations.

PMID- 23536696
TI  - Development of advanced electron holographic techniques and application to
      industrial materials and devices.
AB  - The development of a transmission electron microscope equipped with a field
      emission gun paved the way for electron holography to be put to practical use in
      various fields. In this paper, we review three advanced electron holography
      techniques: on-line real-time electron holography, three-dimensional (3D)
      tomographic holography and phase-shifting electron holography, which are becoming
      important techniques for materials science and device engineering. We also
      describe some applications of electron holography to the analysis of industrial
      materials and devices: GaAs compound semiconductors, solid oxide fuel cells and
      all-solid-state lithium ion batteries.

PMID- 23536695
TI  - Lactobacillus rhamnosus ingestion promotes innate host defense in an enteric
      parasitic infection.
AB  - Enteric parasite infections around the world are a huge economic burden and
      decrease the quality of life for many people. The use of beneficial bacteria has
      attracted attention for their potential therapeutic applications in various
      diseases. However, the effects of beneficial bacteria in enteric parasitic
      infections remain largely unexplored. We investigated the effects of ingestion of
      Lactobacillus rhamnosus (JB-1) in a model of enteric nematode (Trichuris muris)
      infection. C57BL/6 (resistant to infection), AKR (susceptible to infection),
      interleukin 10 (IL-10) knockout (KO), and mucin Muc2 KO mice were infected with
      T. muris and treated orally with probiotic JB-1 or medium. The mice were
      sacrificed on various days postinfection to examine goblet cells, epithelial cell
      proliferation, cytokines, and worm burdens. Treatment with JB-1 significantly
      enhanced worm expulsion in resistant C57BL/6 mice, and this was associated with
      increases in IL-10 levels, goblet cell numbers, and epithelial cell
      proliferation. Beneficial effects of JB-1 were absent in IL-10 KO and resistant
      mice treated with gamma-irradiated bacteria. Live JB-1 treatment also expedited
      worm expulsion in Muc2 KO mice and, more importantly, in AKR mice (susceptible to
      infection). Injection of IL-10 directly into the colonic tissue of uninfected
      mice induced goblet cell hyperplasia. These findings demonstrate that JB-1
      modulates goblet cell biology and promotes parasite expulsion via an IL-10
      mediated pathway and provide novel insights into probiotic effects on innate
      defense in nematode infection.

PMID- 23536697
TI  - Coherence of k-space electrons: application to TDS electrons by DBI.
AB  - Methods of controlled electron interference in k-space on the diffraction plane
      by means of an electron biprism invented during the Tonomura Electron Wavefront
      Project are briefly reviewed. The results presented show the partial coherence of
      self-interfered diffusely scattered electrons, elastically scattered and
      inelastically scattered, found outside and in between the Bragg diffracted beams
      often referred to as thermal diffuse scattering (TDS) of electrons. The
      interference fringes formed in the TDS intensity have been used to calculate a
      mean displacement of the atom of u ~ 12 pm in Aluminum in the direction
      perpendicular to the Bragg planes.

PMID- 23536698
TI  - Interpretation of phase images of delta-doped layers.
AB  - An approach is presented that allows independent determination of the mean inner
      potential contribution to a phase image of a highly doped layer in a
      semiconductor measured using off-axis electron holography, in order to quantify
      the contribution to the recorded phase from the dopant potential alone. The
      method takes into account the possible presence of both substitutional and
      interstitial dopant atoms and is used here to analyse an experimental phase image
      of 12 delta-doped B layers in Si that are separated from each other by <6 nm.

PMID- 23536700
TI  - Phase retrieval from image intensities: why does exit wave restoration using IWFR
      work so well?
AB  - The iterative wave function reconstruction (IWFR) is one type of in-line
      holography and retrieves a complex wave function from a set of through-focus
      images. We have verified that the IWFR provides an extremely good estimate of an
      atomic-resolution exit wave function (EWF) simply from the Fourier transforms of
      observed intensities. Thus, the first guess of the EWF using only five images
      gives all the features of the final result, and the convergence of the IWFR is
      very quick. The IWFR accepts a wide variety of defocus step, and the total
      defocus span or the defocus step is not essential. The absolute defocus can be
      estimated by propagating the EWF to the plane where the propagated wave function
      gives the minimum amplitude variation. Even when there is some error in the
      spherical aberration coefficient, the EWF suffers from only the aberrations due
      to the estimation error. The residual error may be adjusted on the reconstructed
      complex wave function. With the development of a stable microscope it becomes
      more realistic to routinely record multiple images with good quality, which
      allows advanced image processing such as the IWFR. Such an exit wave
      reconstruction is also desirable to investigate a phase object using a Cs
      corrected microscope, since the intentionally introduced aberrations to amplify
      the phase object contrast are desirable to be eliminated by post-processing.

PMID- 23536699
TI  - Phase contrast image simulations for electron holography of magnetic and electric
      fields.
AB  - The research on flux line lattices and pancake vortices in superconducting
      materials, carried out within a long and fruitful collaboration with Akira
      Tonomura and his group at the Hitachi Advanced Research Laboratory, led us to
      develop a mathematical framework, based on the reciprocal representation of the
      magnetic vector potential, that enables us to simulate realistic phase images of
      fluxons. The aim of this paper is to review the main ideas underpinning our
      computational framework and the results we have obtained throughout the
      collaboration. Furthermore, we outline how to generalize the approach to model
      other samples and structures of interest, in particular thin ferromagnetic films,
      ferromagnetic nanoparticles and p-n junctions.

PMID- 23536701
TI  - Exploring aberration-corrected electron microscopy for compound semiconductors.
AB  - The development of aberration-corrected electron microscopes (ACEMs) has made it
      possible to resolve individual atomic columns ('dumbbells') with correct
      interatomic spacings in elemental and compound semiconductors. Thus, the latest
      generations of ACEMs should become powerful instruments for determining detailed
      structural arrangements at defects and interfaces in these materials. This paper
      provides a short overview of off-line ('software') and on-line ('hardware') ACEM
      techniques, with particular reference to characterization of elemental and
      compound semiconductors. Exploratory probe-corrected studies of ZnTe/InP and
      ZnTe/GaAs epitaxial heterostructures and interfacial defects are also described.
      Finally, some of the associated problems and future prospects are briefly
      discussed.

PMID- 23536702
TI  - A stalled retrotranslocation complex reveals physical linkage between substrate
      recognition and proteasomal degradation during ER-associated degradation.
AB  - During endoplasmic reticulum-associated degradation (ERAD), misfolded lumenal and
      membrane proteins in the ER are recognized by the transmembrane Hrd1 ubiquitin
      ligase complex and retrotranslocated to the cytosol for ubiquitination and
      degradation. Although substrates are believed to be delivered to the proteasome
      only after the ATPase Cdc48p/p97 acts, there is limited knowledge about how the
      Hrd1 complex coordinates with Cdc48p/p97 and the proteasome to orchestrate
      substrate recognition and degradation. Here we provide evidence that inactivation
      of Cdc48p/p97 stalls retrotranslocation and triggers formation of a complex that
      contains the 26S proteasome, Cdc48p/p97, ubiquitinated substrates, select
      components of the Hrd1 complex, and the lumenal recognition factor, Yos9p. We
      propose that the actions of Cdc48p/p97 and the proteasome are tightly coupled
      during ERAD. Our data also support a model in which the Hrd1 complex links
      substrate recognition and degradation on opposite sides of the ER membrane.

PMID- 23536703
TI  - Ndufaf5 deficiency in the Dictyostelium model: new roles in autophagy and
      development.
AB  - Ndufaf5 (also known as C20orf7) is a mitochondrial complex I (CI) assembly factor
      whose mutations lead to human mitochondrial disease. Little is known about the
      function of the protein and the cytopathological consequences of the mutations.
      Disruption of Dictyostelium Ndufaf5 leads to CI deficiency and defects in growth
      and development. The predicted sequence of Ndufaf5 contains a putative
      methyltransferase domain. Site-directed mutagenesis indicates that the
      methyltransferase motif is essential for its function. Pathological mutations
      were recreated in the Dictyostelium protein and expressed in the mutant
      background. These proteins were unable to complement the phenotypes, which
      further validates Dictyostelium as a model of the disease. Chronic activation of
      AMP-activated protein kinase (AMPK) has been proposed to play a role in
      Dictyostelium and human cytopathology in mitochondrial diseases. However,
      inhibition of the expression of AMPK gene in the Ndufaf5-null mutant does not
      rescue the phenotypes associated with the lack of Ndufaf5, suggesting that novel
      AMPK-independent pathways are responsible for Ndufaf5 cytopathology. Of interest,
      the Ndufaf5-deficient strain shows an increase in autophagy. This phenomenon was
      also observed in a Dictyostelium mutant lacking MidA (C2orf56/PRO1853/Ndufaf7),
      another CI assembly factor, suggesting that autophagy activation might be a
      common feature in mitochondrial CI dysfunction.

PMID- 23536704
TI  - Divergent modes for cargo-mediated control of clathrin-coated pit dynamics.
AB  - Clathrin-mediated endocytosis has long been viewed as a process driven by core
      endocytic proteins, with internalized cargo proteins being passive. In contrast,
      an emerging view suggests that signaling receptor cargo may actively control its
      fate by regulating the dynamics of clathrin-coated pits (CCPs) that mediate their
      internalization. Despite its physiological implications, very little is known
      about such "cargo-mediated regulation" of CCPs by signaling receptors. Here,
      using multicolor total internal reflection fluorescence microscopy imaging and
      quantitative analysis in live cells, we show that the MU-opioid receptor, a
      physiologically relevant G protein-coupled signaling receptor, delays the
      dynamics of CCPs in which it is localized. This delay is mediated by the
      interactions of two critical leucines on the receptor cytoplasmic tail. Unlike
      the previously known mechanism of cargo-mediated regulation, these residues
      regulate the lifetimes of dynamin, a key component of CCP scission. These results
      identify a novel means for selectively controlling the endocytosis of distinct
      cargo that share common trafficking components and indicate that CCP regulation
      by signaling receptors can operate via divergent modes.

PMID- 23536705
TI  - A short carboxyl-terminal tail is required for single-stranded DNA binding,
      higher-order structural organization, and stability of the mitochondrial single
      stranded annealing protein Mgm101.
AB  - Mgm101 is a Rad52-type single-stranded annealing protein (SSAP) required for
      mitochondrial DNA (mtDNA) repair and maintenance. Structurally, Mgm101 forms
      large oligomeric rings. Here we determine the function(s) of a 32-amino acid
      carboxyl-terminal tail (Mgm101(238-269)) conserved in the Mgm101 family of
      proteins. Mutagenic analysis shows that Lys-253, Trp-257, Arg-259, and Tyr-268
      are essential for mtDNA maintenance. Mutations in Lys-251, Arg-252, Lys-260, and
      Tyr-266 affect mtDNA stability at 37 degrees C and under oxidative stress. The
      Y268A mutation severely affects single-stranded DNA (ssDNA) binding without
      altering the ring structure. Mutations in the Lys-251-Arg-252-Lys-253 positive
      triad also affect ssDNA binding. Moreover, the C-tail alone is sufficient to
      mediate ssDNA binding. Finally, we find that the W257A and R259A mutations
      dramatically affect the conformation and oligomeric state of Mgm101. These
      structural alterations correlate with protein degradation in vivo. The data thus
      indicate that the C-tail of Mgm101, likely displayed on the ring surface, is
      required for ssDNA binding, higher-order structural organization, and protein
      stability. We speculate that an initial electrostatic and base-stacking
      interaction with ssDNA could remodel ring organization. This may facilitate the
      formation of nucleoprotein filaments competent for mtDNA repair. These findings
      could have broad implications for understanding how SSAPs promote DNA repair and
      genome maintenance.

PMID- 23536706
TI  - Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation.
AB  - In neuronal development, dendritic spine formation is important for the
      establishment of excitatory synaptic connectivity and functional neural circuits.
      Developmental deficiency in spine formation results in multiple neuropsychiatric
      disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been
      reported as a candidate genetic risk factor for autism, dyslexia, and
      schizophrenia. We previously showed that Dock4 is expressed in hippocampal
      neurons. However, the functions of Dock4 in hippocampal neurons and the
      underlying molecular mechanisms are poorly understood. Here we show that Dock4 is
      highly concentrated in dendritic spines and implicated in spine formation via
      interaction with the actin-binding protein cortactin. In cultured neurons, short
      hairpin RNA (shRNA)-mediated knockdown of Dock4 reduces dendritic spine density,
      which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a
      GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding
      region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine
      formation. Taken together, the results show a novel and functionally important
      interaction between Dock4 and cortactin for regulating dendritic spine formation
      via activation of Rac.

PMID- 23536707
TI  - Activation of the FGF2-FGFR1 autocrine pathway: a novel mechanism of acquired
      resistance to gefitinib in NSCLC.
AB  - Patients with non-small cell lung cancer (NSCLC) that harbors epidermal growth
      factor receptor (EGFR) mutations initially respond to EGFR-tyrosine kinase
      inhibitors (TKI) but eventually experience relapse. Acquired resistance to EGFR
      TKIs is strongly associated with patient mortality. Thus, elucidation of the
      mechanism of acquired resistance to EGFR-TKIs is of great importance. In this
      study, gefitinib-resistant cell line models were established by long-term
      exposure to gefitinib using the gefitinib-sensitive lung cancer cell lines, PC9
      and HCC827. Expression analyses indicated that both FGFR1 and FGF2 were increased
      in PC9 gefitinib-resistant (PC9 GR) cells as compared with PC9 naive (PC9 na)
      cells. Importantly, proliferation of gefitinib-resistant cells was dependent on
      the FGF2 -FGFR1 pathway. Mechanistically, inhibition of either FGF2 or FGFR1 by
      siRNA or FGFR inhibitor (PD173074) restored gefitinib sensitivity in PC9 GR
      cells. These data suggest that FGF2 -FGFR1 activation through an autocrine loop
      is a novel mechanism of acquired resistance to EGFR-TKIs.

PMID- 23536708
TI  - Mechanisms of human motor cortex facilitation induced by subthreshold 5-Hz
      repetitive transcranial magnetic stimulation.
AB  - Our knowledge about the mechanisms of human motor cortex facilitation induced by
      repetitive transcranial magnetic stimulation (rTMS) is still incomplete. Here we
      used pharmacological conditioning with carbamazepine, dextrometorphan, lorazepam,
      and placebo to elucidate the type of plasticity underlying this facilitation, and
      to probe if mechanisms reminiscent of long-term potentiation are involved. Over
      the primary motor cortex of 10 healthy subjects, we applied biphasic rTMS pulses
      of effective posterior current direction in the brain. We used six blocks of 200
      pulses at 5-Hz frequency and 90% active motor threshold intensity and controlled
      for corticospinal excitability changes using motor-evoked potential (MEP)
      amplitudes and latencies elicited by suprathreshold pulses before, in between,
      and after rTMS. Target muscle was the dominant abductor digiti minimi muscle; we
      coregistered the dominant extensor carpi radialis muscle. We found a lasting
      facilitation induced by this type of rTMS. The GABAergic medication lorazepam and
      to a lesser extent the ion channel blocker carbamazepine reduced the MEP
      facilitation after biphasic effective posteriorly oriented rTMS, whereas the N
      methyl-d-aspartate receptor-antagonist dextrometorphan had no effect. Our main
      conclusion is that the mechanism of the facilitation induced by biphasic
      effective posterior rTMS is more likely posttetanic potentiation than long-term
      potentiation. Additional findings were prolonged MEP latency under carbamazepine,
      consistent with sodium channel blockade, and larger MEP amplitudes from extensor
      carpi radialis under lorazepam, suggesting GABAergic involvement in the center
      surround balance of excitability.

PMID- 23536709
TI  - Transfer of ballistic motor skill between bilateral and unilateral contexts in
      young and older adults: neural adaptations and behavioral implications.
AB  - Bilateral movement rehabilitation is gaining popularity as an approach to improve
      the recovery not only of bimanual function but also of unilateral motor tasks.
      While the neural mechanisms mediating the transfer of bilateral training gains
      into unimanual contexts are not fully understood, converging evidence from
      behavioral, neurophysiological, and imaging studies suggests that bimanual
      movements are not simply the superposition of unimanual tasks undertaken with
      both (upper) limbs. Here we investigated the neural responses in both hemispheres
      to bilateral ballistic motor training and the extent to which performance
      improvements transferred to a unimanual task. Since aging influences
      interhemispheric interactions during movement production, both young (n = 9; mean
      age 19.4 yr; 6 women, 3 men) and older (n = 9; 66.3 yr; 7 women, 2 men) adults
      practiced a bilateral motor task requiring simultaneous "fast-as-possible"
      abductions of their left and right index fingers. Changes in bilateral and
      unilateral performance, and in corticospinal excitability and intracortical
      inhibition, were assessed. Strong transfer was observed between bimanual and
      unimanual contexts for both age groups. However, in contrast to previous reports
      of substantial bilateral cortical adaptations following unilateral training,
      increases in corticospinal excitability following bilateral training were not
      statistically reliable, and a release of intracortical inhibition was only
      observed for older adults. The results indicate that the neural mechanisms of
      motor learning for bilateral ballistic tasks differ from those that underlie
      unimanual ballistic performance improvement but that aging results in a greater
      overlap of the neural mechanisms mediating bilateral and unilateral ballistic
      motor performance.

PMID- 23536711
TI  - Short- and long-latency interhemispheric inhibitions are additive in human motor
      cortex.
AB  - Transcranial magnetic stimulation (TMS) of the human primary motor cortex (M1) at
      suprathreshold strength results in inhibition of M1 in the opposite hemisphere, a
      process termed interhemispheric inhibition (IHI). Two phases of IHI, termed short
      latency interhemispheric inhibition (SIHI) and long-latency interhemispheric
      inhibition (LIHI), involving separate neural circuits, have been identified. In
      this study we evaluated how these two inhibitory processes interact with each
      other. We studied 10 healthy right-handed subjects. A test stimulus (TS) was
      delivered to the left M1, and motor evoked potentials (MEPs) were recorded from
      the right first dorsal interosseous (FDI) muscle. Contralateral conditioning
      stimuli (CCS) were applied to the right M1 either 10 ms or 50 ms prior to the TS,
      inducing SIHI and LIHI, respectively, in the left M1. The effects of SIHI and
      LIHI alone, and SIHI and LIHI delivered together, were compared. The TS was
      adjusted to produce 1-mV or 0.5-mV MEPs when applied alone or after CCS. SIHI and
      LIHI were found to be additive when delivered together, irrespective of the
      strength of the TS. The interactions were affected neither by varying the
      strength of the conditioning stimulus producing SIHI nor by altering the current
      direction of the TS. Small or opposing interactions, however, may not have been
      detected. These results support previous findings suggesting that SIHI and LIHI
      act through different neural circuits. Such inhibitory processes may be used
      individually or additively during motor tasks and should be studied as separate
      processes in functional studies.

PMID- 23536710
TI  - Postnatal development of synaptic properties of the GABAergic projection from the
      inferior colliculus to the auditory thalamus.
AB  - The development of auditory temporal processing is important for processing
      complex sounds as well as for acquiring reading and language skills. Neuronal
      properties and sound processing change dramatically in auditory cortex neurons
      after the onset of hearing. However, the development of the auditory thalamus or
      medial geniculate body (MGB) has not been well studied over this critical time
      window. Since synaptic inhibition has been shown to be crucial for auditory
      temporal processing, this study examined the development of a feedforward,
      GABAergic connection to the MGB from the inferior colliculus (IC), which is also
      the source of sensory glutamatergic inputs to the MGB. IC-MGB inhibition was
      studied using whole cell patch-clamp recordings from rat brain slices in current
      clamp and voltage-clamp modes at three age groups: a prehearing group [postnatal
      day (P)7-P9], an immediate posthearing group (P15-P17), and a juvenile group (P22
      P32) whose neuronal properties are largely mature. Membrane properties matured
      substantially across the ages studied. GABAA and GABAB inhibitory postsynaptic
      potentials were present at all ages and were similar in amplitude. Inhibitory
      postsynaptic potentials became faster to single shocks, showed less depression to
      train stimuli at 5 and 10 Hz, and were overall more efficacious in controlling
      excitability with age. Overall, IC-MGB inhibition becomes faster and more precise
      during a time period of rapid changes across the auditory system due to the
      codevelopment of membrane properties and synaptic properties.

PMID- 23536712
TI  - Differences in movement-related cortical activation patterns underlying motor
      performance in children with and without developmental coordination disorder.
AB  - Behavioral deficits in visuomotor planning and control exhibited by children with
      developmental coordination disorder (DCD) have been extensively reported.
      Although these functional impairments are thought to result from "atypical brain
      development," very few studies to date have identified potential neurological
      mechanisms. To address this knowledge gap, electroencephalography (EEG) was
      recorded from 6- to 12-yr-old children with and without DCD (n = 14 and 20,
      respectively) during the performance of a visuomotor drawing task. With respect
      to motor performance, typically developing (TD) children exhibited age-related
      improvements in key aspects of motor planning and control. Although some children
      with DCD performed outside this TD landscape (i.e., age-related changes within
      the TD group), the group developmental trajectory of the children with DCD was
      similar to that of the TD children. Despite overall similarities in performance,
      engagement of cortical resources in the children with DCD was markedly different
      from that in their TD counterparts. While the patterns of activation are stable
      in TD children across the age range, the young children with DCD exhibited less
      engagement of motor cortical brain areas and the older children with DCD
      exhibited greater engagement of motor cortical brain areas than their TD peers.
      These results suggest that older children with DCD may employ a compensatory
      strategy in which increased engagement of relevant motor resources allows these
      children to perform comparably to their TD peers. Moreover, the magnitude of
      activation was related to several kinematic measures, particularly in children
      with DCD, suggesting that greater engagement in motor resources may underlie
      better behavioral performance.

PMID- 23536713
TI  - Interaction between cognitive and motor cortico-basal ganglia loops during
      decision making: a computational study.
AB  - In a previous modeling study, Leblois et al. (2006) demonstrated an action
      selection mechanism in cortico-basal ganglia loops based on competition between
      the positive feedback, direct pathway through the striatum and the negative
      feedback, hyperdirect pathway through the subthalamic nucleus. The present study
      investigates how multiple level action selection could be performed by the basal
      ganglia. To do this, the model is extended in a manner consistent with known
      anatomy and electrophysiology in three main areas. First, two-level decision
      making has been incorporated, with a cognitive level selecting based on cue shape
      and a motor level selecting based on cue position. We show that the decision made
      at the cognitive level can be used to bias the decision at the motor level. We
      then demonstrate that, for accurate transmission of information between decision
      making levels, low excitability of striatal projection neurons is necessary, a
      generally observed electrophysiological finding. Second, instead of providing a
      biasing signal between cue choices as an external input to the network, we show
      that the action selection process can be driven by reasonable levels of noise.
      Finally, we incorporate dopamine modulated learning at corticostriatal synapses.
      As learning progresses, the action selection becomes based on learned visual cue
      values and is not interfered with by the noise that was necessary before
      learning.

PMID- 23536714
TI  - State-based decoding of hand and finger kinematics using neuronal ensemble and
      LFP activity during dexterous reach-to-grasp movements.
AB  - The performance of brain-machine interfaces (BMIs) that continuously control
      upper limb neuroprostheses may benefit from distinguishing periods of posture and
      movement so as to prevent inappropriate movement of the prosthesis. Few studies,
      however, have investigated how decoding behavioral states and detecting the
      transitions between posture and movement could be used autonomously to trigger a
      kinematic decoder. We recorded simultaneous neuronal ensemble and local field
      potential (LFP) activity from microelectrode arrays in primary motor cortex (M1)
      and dorsal (PMd) and ventral (PMv) premotor areas of two male rhesus monkeys
      performing a center-out reach-and-grasp task, while upper limb kinematics were
      tracked with a motion capture system with markers on the dorsal aspect of the
      forearm, hand, and fingers. A state decoder was trained to distinguish four
      behavioral states (baseline, reaction, movement, hold), while a kinematic decoder
      was trained to continuously decode hand end point position and 18 joint angles of
      the wrist and fingers. LFP amplitude most accurately predicted transition into
      the reaction (62%) and movement (73%) states, while spikes most accurately
      decoded arm, hand, and finger kinematics during movement. Using an LFP-based
      state decoder to trigger a spike-based kinematic decoder [r = 0.72, root mean
      squared error (RMSE) = 0.15] significantly improved decoding of reach-to-grasp
      movements from baseline to final hold, compared with either a spike-based state
      decoder combined with a spike-based kinematic decoder (r = 0.70, RMSE = 0.17) or
      a spike-based kinematic decoder alone (r = 0.67, RMSE = 0.17). Combining LFP
      based state decoding with spike-based kinematic decoding may be a valuable step
      toward the realization of BMI control of a multifingered neuroprosthesis
      performing dexterous manipulation.

PMID- 23536715
TI  - Preserving axosomatic spiking features despite diverse dendritic morphology.
AB  - Throughout the nervous system, cells belonging to a certain electrical class (e
      class)-sharing high similarity in firing response properties-may nevertheless
      have widely variable dendritic morphologies. To quantify the effect of this
      morphological variability on the firing of layer 5 thick-tufted pyramidal cells
      (TTCs), a detailed conductance-based model was constructed for a three
      dimensional reconstructed exemplar TTC. The model exhibited spike initiation in
      the axon and reproduced the characteristic features of individual spikes, as well
      as of the firing properties at the soma, as recorded in a population of TTCs in
      young Wistar rats. When using these model parameters over the population of 28
      three-dimensional reconstructed TTCs, both axonal and somatic ion channel
      densities had to be scaled linearly with the conductance load imposed on each of
      these compartments. Otherwise, the firing of model cells deviated, sometimes very
      significantly, from the experimental variability of the TTC e-class. The study
      provides experimentally testable predictions regarding the coregulation of
      axosomatic membrane ion channels density for cells with different dendritic
      conductance load, together with a simple and systematic method for generating
      reliable conductance-based models for the whole population of modeled neurons
      belonging to a particular e-class, with variable morphology as found
      experimentally.

PMID- 23536716
TI  - The representation of tool and non-tool object information in the human
      intraparietal sulcus.
AB  - Humans have an amazing ability to quickly and efficiently recognize and interact
      with visual objects in their environment. The underlying neural processes
      supporting this ability have been mainly explored in the ventral visual stream.
      However, the dorsal stream has been proposed to play a critical role in guiding
      object-directed actions. This hypothesis is supported by recent neuroimaging
      studies that have identified object-selective and tool-related activity in human
      parietal cortex. In the present study, we sought to delineate tool-related
      information in the anterior portions of the human intraparietal sulcus (IPS) and
      relate it to recently identified motor-defined and topographic regions of
      interest (ROIs) using functional MRI in individual subjects. Consistent with
      previous reports, viewing pictures of tools compared with pictures of animals led
      to a higher blood oxygenation level-dependent (BOLD) response in the left
      anterior IPS. For every subject, this activation was located lateral, anterior,
      and inferior to topographic area IPS5 and lateral and inferior to a motor-defined
      human parietal grasp region (hPGR). In a separate experiment, subjects viewed
      pictures of tools, animals, graspable (non-tool) objects, and scrambled objects.
      An ROI-based time-course analysis showed that tools evoked a stronger BOLD
      response than animals throughout topographic regions of the left IPS.
      Additionally, graspable objects evoked stronger responses than animals, equal to
      responses to tools, in posterior regions and weaker responses than tools, equal
      to responses to animals, in anterior regions. Thus the left anterior tool
      specific region may integrate visual information encoding graspable features of
      objects from more posterior portions of the IPS with experiential knowledge of
      object use and function to guide actions.

PMID- 23536717
TI  - Representation of tactile curvature in macaque somatosensory area 2.
AB  - Tactile shape information is elaborated in a cortical hierarchy spanning primary
      (SI) and secondary somatosensory cortex (SII). Indeed, SI neurons in areas 3b and
      1 encode simple contour features such as small oriented bars and edges, whereas
      higher order SII neurons represent large curved contour features such as angles
      and arcs. However, neural coding of these contour features has not been
      systematically characterized in area 2, the most caudal SI subdivision in the
      postcentral gyrus. In the present study, we analyzed area 2 neural responses to
      embossed oriented bars and curved contour fragments to establish whether
      curvature representations are generated in the postcentral gyrus. We found that
      many area 2 neurons (26 of 112) exhibit clear curvature tuning, preferring
      contours pointing in a particular direction. Fewer area 2 neurons (15 of 112)
      show preferences for oriented bars. Because area 2 response patterns closely
      resembled SII patterns, we also compared area 2 and SII response time courses to
      characterize the temporal dynamics of curvature synthesis in the somatosensory
      system. We found that curvature representations develop and peak concurrently in
      area 2 and SII. These results reveal that transitions from orientation tuning to
      curvature selectivity in the somatosensory cortical hierarchy occur within SI
      rather than between SI and SII.

PMID- 23536718
TI  - Responses of single corticospinal neurons to intracortical stimulation of primary
      motor and premotor cortex in the anesthetized macaque monkey.
AB  - The responses of individual primate corticospinal neurons to localized electrical
      stimulation of primary motor (M1) and of ventral premotor cortex (area F5) are
      poorly documented. To rectify this and to study interactions between responses
      from these areas, we recorded corticospinal axons, identified by pyramidal tract
      stimulation, in the cervical spinal cord of three chloralose-anesthetized macaque
      monkeys. Single stimuli (<=400 MUA) were delivered to the hand area of M1 or F5
      through intracortical microwire arrays. Only 14/112 (13%) axons showed responses
      to M1 stimuli that indicated direct intracortical activation of corticospinal
      neurons (D-responses); no D-responses were seen from F5. In contrast, 62 axons
      (55%) exhibited consistent later responses to M1 stimulation, corresponding to
      indirect activation (I-responses), showing that single-pulse intracortical
      stimulation of motor areas can result in trans-synaptic activation of a high
      proportion of the corticospinal output. A combined latency histogram of all axon
      responses was nonperiodic, clearly different from the periodic surface-recorded
      corticospinal volleys. This was readily explained by correcting for conduction
      velocities of individual axons. D-responding axons, taken as originating in
      neurons close to the M1 stimulating electrodes, showed more I-responses from M1
      than those without a D-response, and 8/10 of these axons also responded to F5
      stimulation. Altogether, 33% of tested axons responded to F5 stimulation, most of
      which also showed I-responses from M1. These excitatory effects are in keeping
      with facilitation of hand muscles evoked from F5 being relayed via M1. This was
      further demonstrated by facilitation of test responses from M1 by conditioning F5
      stimuli.

PMID- 23536719
TI  - Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor,
      in treating drug resistance and preventing cancer cell migration and invasion.
AB  - CUDC-101 is a novel, small-molecule, anticancer agent targeting histone
      deacetylase (HDAC), EGF receptor (EGFR), and HER2. It is currently in phase I
      clinical development in patients with solid tumors. Previously, we reported that
      CUDC-101 has potent antiproliferative and proapoptotic activity in cultured tumor
      cells and in vivo xenograft models. We now show that cancer cells that have
      acquired resistance to single-target EGFR inhibitors through upregulation of AXL
      or loss of E-cadherin remain sensitive to CUDC-101, which inhibits MET- and AXL
      mediated signaling, restores E-cadherin expression, and reduces cell migration.
      CUDC-101 also efficiently inhibited the proliferation of MET-overexpressing non
      small cell lung cancer and gastric cancer cell lines and inhibited the migration
      and invasion of invasive tumor cells. Taken together, these results suggest that
      coupling HDAC and HER2 inhibitory activities to an EGFR inhibitor may potentially
      be effective in overcoming drug resistance and preventing cancer cell migration.

PMID- 23536720
TI  - HGF as a circulating biomarker of onartuzumab treatment in patients with advanced
      solid tumors.
AB  - The objective of this study was to evaluate circulating hepatocyte growth factor
      (cHGF) as a pharmacodynamic biomarker of Met inhibition for onartuzumab (MetMAb,
      OA5D5v2) in a phase I trial in patients with advanced cancers and a phase II
      trial in non-small cell lung cancer (NSCLC). The phase I study was a dose
      escalation trial with onartuzumab administered i.v. once every three weeks. The
      phase II study was a randomized two-arm trial in which onartuzumab or placebo was
      administered in combination with erlotinib in 137 patients with second and third
      line (2/3L) NSCLC. cHGF levels were evaluated by ELISA at multiple time points
      over the treatment period. Onartuzumab administration resulted in an acute and
      sustained rise in cHGF in both the phase I and phase II studies. Elevation in
      cHGF was independent of dose or drug exposure and was restricted to onartuzumab
      treatment. Neither higher baseline nor elevated change in cHGF levels upon
      treatment could simply be attributed to tumor burden or number of liver
      metastasis. We have shown that elevated cHGF can consistently and reproducibly be
      measured as a pharmacodynamic biomarker of onartuzumab activity. The elevation in
      cHGF is independent of tumor type, dose administered, or dose duration. Although
      these studies were not powered to directly address the contribution of cHGF as a
      predictive, on-treatment, circulating biomarker, these data suggest that
      measurement of cHGF in future expanded studies is warranted.

PMID- 23536721
TI  - The novel Chk1 inhibitor MK-8776 sensitizes human leukemia cells to HDAC
      inhibitors by targeting the intra-S checkpoint and DNA replication and repair.
AB  - Interactions between the novel Chk1 inhibitor MK-8776 and the histone deacetylase
      (HDAC) inhibitor (HDACI) vorinostat were examined in human leukemia cells
      harboring wild-type (wt) or deficient p53. MK-8776 synergistically potentiated
      vorinostat-mediated apoptosis in various p53-wt or -deficient leukemia cell
      lines, whereas p53 knockdown by short hairpin RNA (shRNA) sensitized p53-wt cells
      to lethality of this regimen. Leukemia cell lines carrying FLT3-ITD were also
      sensitive to the MK-8776/vorinostat regimen. Synergistic interactions were
      associated with inhibition of Chk1 activity, interference with the intra-S-phase
      checkpoint, disruption of DNA replication, and downregulation of proteins
      involved in DNA replication (e.g., Cdt1) and repair (e.g., CtIP and BRCA1),
      resulting in sharp increases in DNA damage, reflected by enhanced gamma-H2A.X
      formation, and apoptosis. Moreover, leukemia cells expressing kinase-dead Chk1
      (D130A) or Chk1 shRNA were significantly more sensitive to HDACIs compared with
      their wt counterparts and displayed downregulation of CtIP and BRCA1
      phosphorylation following HDACI exposure. Finally, the MK-8776/vorinostat regimen
      was active in primary acute myelogenous leukemia (AML) blasts, particularly
      against the CD34(+)/CD38(-)/CD123(+) population enriched for leukemia-initiating
      cells. In contrast, identical regimens were relatively sparing toward normal cord
      blood CD34(+) cells. Together, these findings indicate that the novel Chk1
      inhibitor MK-8776 markedly potentiates HDACI lethality in leukemia cells
      displaying various genetic backgrounds through mechanisms involving disruption of
      the intra-S checkpoint, DNA replication, and DNA repair. They also argue that
      leukemic cells, including those bearing oncogenic mutations associated with poor
      prognosis, for example, p53 deletion/mutation or FLT3-ITD, may also be
      susceptible to this strategy.

PMID- 23536722
TI  - Endothelial cells enhance prostate cancer metastasis via IL-6->androgen receptor
      >TGF-beta->MMP-9 signals.
AB  - Although the potential roles of endothelial cells in the microvascules of
      prostate cancer during angiogenesis have been documented, their direct impacts on
      the prostate cancer metastasis remain unclear. We found that the CD31-positive
      and CD34-positive endothelial cells are increased in prostate cancer compared
      with the normal tissues and that these endothelial cells were decreased upon
      castration, gradually recovered with time, and increased after prostate cancer
      progressed into the castration-resistant stage, suggesting a potential linkage of
      these endothelial cells with androgen deprivation therapy. The in vitro invasion
      assays showed that the coculture of endothelial cells with prostate cancer cells
      significantly enhanced the invasion ability of the prostate cancer cells.
      Mechanism dissection found that coculture of prostate cancer cells with
      endothelial cells led to increased interleukin (IL)-6 secretion from endothelial
      cells, which may result in downregulation of androgen receptor (AR) signaling in
      prostate cancer cells and then the activation of TGF-beta/matrix
      metalloproteinase-9 (MMP-9) signaling. The consequences of the IL-6->AR->TGFbeta
      >MMP-9 signaling pathway might then trigger the increased invasion of prostate
      cancer cells. Blocking the IL-6->AR->TGFbeta->MMP-9 signaling pathway either by
      IL-6 antibody, AR-siRNA, or TGF-beta1 inhibitor all interrupted the ability of
      endothelial cells to influence prostate cancer invasion. These results, for the
      first time, revealed the important roles of endothelial cells within the prostate
      cancer microenvironment to promote the prostate cancer metastasis and provide new
      potential targets of IL-6->AR->TGFbeta->MMP-9 signals to battle the prostate
      cancer metastasis.

PMID- 23536723
TI  - Suppression of survivin induced by a BCR-ABL/JAK2/STAT3 pathway sensitizes
      imatinib-resistant CML cells to different cytotoxic drugs.
AB  - The BCR-ABL oncoprotein of chronic myelogenous leukemia (CML) displays exclusive
      cytoplasmic localization and constitutive tyrosine kinase activity leading to the
      activation of different pathways that favor cell proliferation and survival. BCR
      ABL induces survivin expression at both the mRNA and protein level, thus
      inhibiting the apoptotic machinery of CML cells and contributing to the expansion
      of the leukemic clone. We report that, in human CML cell lines, BCR-ABL-mediated
      upregulation of survivin involves the JAK2/STAT3 pathway since silencing of
      either protein caused a consistent reduction in survivin expression. Cell lines
      unresponsive to imatinib mesylate (IM) because of BCR-ABL gene amplification were
      not resensitized to the drug after survivin downregulation. However, cells
      insensitive to IM because of point mutations in the BCR-ABL kinase domain were
      highly responsive to hydroxyurea (HU) after survivin silencing. To address the
      possible clinical applications of our results, we used shepherdin, a cell
      permeable peptidomimetic compound that downregulates survivin expression by
      preventing its interaction with Hsp90. Incubation with shepherdin of immortalized
      cell lines both sensitive and resistant to IM enhanced cell death induced by HU
      and doxorubicin. Similarly, the combination of shepherdin with first- and second
      generation tyrosine kinase inhibitors reduced the colony-forming potential of
      human progenitors derived from both patients with IM-sensitive and IM-resistant
      CML. These results suggest that strategies aimed at reducing survivin levels may
      represent a potential therapeutic option for patients with CML unresponsive to
      IM.

PMID- 23536724
TI  - Discovery of the novel mTOR inhibitor and its antitumor activities in vitro and
      in vivo.
AB  - The phosphoinositide 3-kinase (PI3-K)/Akt and mTOR signaling pathway plays a
      critical role in cell survival and proliferation and is often aberrantly
      activated in many types of cancer. The mTOR kinase protein, one of the key
      molecules in this pathway, has been shown to be an important target for cancer
      therapy. In the present study, a ligand docking method was used to screen for
      novel scaffold mTOR inhibitors. Sixty thousand compounds in the Natural Product
      Database were screened against the mTOR homologous structure, and 13 commercially
      available compounds listed in the top-ranked 100 compounds were selected for
      further examination. Compound [(E)-3-(4-(benzo[d][1,3]dioxol-5-yl)-2-oxobut-3-en
      1-yl)- 3-hydroxyindolin-2-one; designated herein as 3HOI-BA-01] was then selected
      for further study of its antitumor activity. An in vitro study has shown that
      3HOI-BA-01 inhibited mTOR kinase activity in a dose-dependent manner by directly
      binding with mTOR. In a panel of non-small cell lung cancer cells, the compound
      also attenuated mTOR downstream signaling, including the phosphorylation of
      p70S6K, S6, and Akt, resulting in G1 cell-cycle arrest and growth inhibition.
      Results of an in vivo study have shown that intraperitoneal injection of 3HOI-BA
      01 in A549 lung tumor-bearing mice effectively suppressed cancer growth without
      affecting the body weight of the mice. The expression of downstream signaling
      molecules in the mTOR pathway in tumor tissues was also reduced after 3HOI-BA-01
      treatment. Taken together, we identified 3HOI-BA-01 as a novel and effective mTOR
      inhibitor.

PMID- 23536726
TI  - Discovery of a novel orally active small-molecule gp130 inhibitor for the
      treatment of ovarian cancer.
AB  - Interleukin (IL)-6 and Stat3 play key roles in ovarian cancer progression.
      However, the role of glycoprotein 130 (gp130), the signal transducer of this
      signaling axis, is not well-established. Currently, there are no small-molecule
      inhibitors of gp130 under clinical development. In this study, we show that gp130
      is an attractive drug target in ovarian cancer due to its role in promoting
      cancer progression via the activation of its downstream Stat3 signaling. We also
      present preclinical studies of SC144, the first-in-class orally active small
      molecule gp130 inhibitor. SC144 shows greater potency in human ovarian cancer
      cell lines than in normal epithelial cells. SC144 binds gp130, induces gp130
      phosphorylation (S782) and deglycosylation, abrogates Stat3 phosphorylation and
      nuclear translocation, and further inhibits the expression of downstream target
      genes. In addition, SC144 shows potent inhibition of gp130 ligand-triggered
      signaling. Oral administration of SC144 delays tumor growth in a mouse xenograft
      model of human ovarian cancer without significant toxicity to normal tissues.

PMID- 23536725
TI  - Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma
      model.
AB  - Multiple myeloma is a hematologic malignancy characterized by the proliferation
      of neoplastic plasma cells in the bone marrow. Although the first-to-market
      proteasome inhibitor bortezomib (Velcade) has been successfully used to treat
      patients with myeloma, drug resistance remains an emerging problem. In this
      study, we identify signatures of bortezomib sensitivity and resistance by gene
      expression profiling (GEP) using pairs of bortezomib-sensitive (BzS) and
      bortezomib-resistant (BzR) cell lines created from the Bcl-XL/Myc double
      transgenic mouse model of multiple myeloma. Notably, these BzR cell lines show
      cross-resistance to the next-generation proteasome inhibitors, MLN2238 and
      carfilzomib (Kyprolis) but not to other antimyeloma drugs. We further
      characterized the response to bortezomib using the Connectivity Map database,
      revealing a differential response between these cell lines to histone deacetylase
      (HDAC) inhibitors. Furthermore, in vivo experiments using the HDAC inhibitor
      panobinostat confirmed that the predicted responder showed increased sensitivity
      to HDAC inhibitors in the BzR line. These findings show that GEP may be used to
      document bortezomib resistance in myeloma cells and predict individual
      sensitivity to other drug classes. Finally, these data reveal complex
      heterogeneity within multiple myeloma and suggest that resistance to one drug
      class reprograms resistant clones for increased sensitivity to a distinct class
      of drugs. This study represents an important next step in translating
      pharmacogenomic profiling and may be useful for understanding personalized
      pharmacotherapy for patients with multiple myeloma.

PMID- 23536727
TI  - Expression of leukemia-associated fusion proteins increases sensitivity to
      histone deacetylase inhibitor-induced DNA damage and apoptosis.
AB  - Histone deacetylase inhibitors (HDI) show activity in a broad range of
      hematologic and solid malignancies, yet the percentage of patients in any given
      malignancy who experience a meaningful clinical response remains small. In this
      study, we sought to investigate HDI efficacy in acute myeloid leukemia (AML)
      cells expressing leukemia-associated fusion proteins (LAFP). HDIs have been shown
      to induce apoptosis, in part, through accumulation of DNA damage and inhibition
      of DNA repair. LAFPs have been correlated with a DNA repair-deficient phenotype,
      which may make them more sensitive to HDI-induced DNA damage. We found that
      expression of the LAFPs PLZF-RARalpha, PML-RARalpha, and RUNX1-ETO (AML1-ETO)
      increased sensitivity to DNA damage and apoptosis induced by the HDI vorinostat.
      The increase in apoptosis correlated with an enhanced downregulation of the
      prosurvival protein BCL2. Vorinostat also induced expression of the cell-cycle
      regulators p19(INK4D) and p21(WAF1) and triggered a G2-M cell cycle arrest to a
      greater extent in LAFP-expressing cells. The combination of LAFP and vorinostat
      further led to a greater downregulation of several base excision repair (BER)
      enzymes. These BER genes represent biomarker candidates for response to HDI
      induced DNA damage. Notably, repair of vorinostat-induced DNA double-strand
      breaks was found to be impaired in PLZF-RARalpha-expressing cells, suggesting a
      mechanism by which LAFP expression and HDI treatment cooperate to cause an
      accumulation of damaged DNA. These data support the continued study of HDI-based
      treatment regimens in LAFP-positive AMLs.

PMID- 23536729
TI  - How do stomata sense reductions in atmospheric relative humidity?

PMID- 23536728
TI  - Tumor suppressor protein p53 negatively regulates human pregnane X receptor
      activity.
AB  - The human pregnane X receptor (PXR) regulates genes involved in drug metabolism
      and disposition. PXR associates with multiple corepressors that attenuate and
      coactivators that enhance its activity. PXR plays a vital role in the drug
      metabolism pathway, and a comprehensive examination of PXR-associated proteins
      will provide greater insight into the regulation of the receptor and possible
      therapeutic implications. We performed a mass spectrometric screen to identify
      PXR-associated proteins. Here we report that the tumor suppressor protein p53 can
      associate with PXR and downregulate its activity. A loss-of-function p53 mutant
      (R175H) interacts with PXR but does not repress its activity. Mutant p53 can
      relieve the suppressive effect of wild-type p53 by competing with its interaction
      with PXR, suggesting that protein-protein interaction is required but not
      sufficient for p53 to repress PXR activity. Interestingly, a PXR variant with a
      naturally occurring deletion of a conserved, unique sequence in the ligand
      binding domain (PXR174-210) did not interact with p53, indicating that the PXR
      p53 interaction is specific. Using a chromatin immunoprecipitation assay, we
      showed that p53 inhibits the binding of PXR to the CYP3A4 promoter. The loss of
      p53 function in tumor cells leads to aberrant cell proliferation, apoptosis,
      carcinogenesis, and altered sensitivity to chemotherapeutic drugs, whereas PXR
      contributes to chemoresistance in many cancer cells. Our findings show for the
      first time that wild-type p53 can negatively regulate PXR by physically
      associating with it. Thus, PXR and p53 appear to play important yet opposing
      roles in the sensitivity of tumor cells to chemotherapy.

PMID- 23536730
TI  - Editorial.

PMID- 23536731
TI  - My learned friends.

PMID- 23536732
TI  - Discrepancy and error in radiology: concepts, causes and consequences.

PMID- 23536733
TI  - Factors influencing performance of cardiopulmonary resuscitation (CPR) by
      Foundation Year 1 hospital doctors.
AB  - BACKGROUND: Foundation Year One (FY1) doctors are often the first medical staff
      responders at in-hospital cardiac arrests. The study objectives were to assess
      the cardiopulmonary resuscitation (CPR) skills of FY1 doctors at a Belfast
      teaching hospital and to highlight factors that influence their performance.
      METHODS: A group of FY1 doctors working in a Belfast teaching hospital were asked
      to participate in this study. These junior doctors were regularly on-call for
      acute medical emergencies including cardiac arrest. Participants were instructed
      to perform two, 3 minute sessions of CPR on a skills reporter manikin. Each
      session was separated by a 5 minute rest period, one session using a compression
      to-ventilation ratio of 15:2 and the other using a ratio of 30:2. Performance was
      gauged both objectively, by measuring the depth of chest compressions, and
      subjectively by a panel of 5 Advanced Life Support (ALS) instructors who reviewed
      the tracings of each CPR session. RESULTS: Overall, 85% of medical FY1's working
      in the hospital participated in the study. Objective results determined that
      males performed significantly better than their female counterparts using both
      the 15:2 and 30:2 ratios. The male FY1 doctors performed equally well using both
      15:2 and 30:2 ratios, in comparison to female doctors who were noted to be better
      using the 15:2 ratio. Individuals with a Body mass index (BMI) greater than the
      mean for the group, performed significantly better than those with a lower BMI
      when using the 30:2 ratio. BMI was an important factor and correlated with chest
      compression depth. Females with a low BMI performed less well when using a ratio
      of 30:2. Overall, expert opinion significantly favoured the 15:2 ratio for the
      FY1 doctor group. CONCLUSION: CPR performance can be influenced by factors such
      as gender and BMI, as such the individual rescuer should take these into account
      when determining which compression to ventilation ration to perform in order to
      maximise patient outcome. This study showed that males and those females with a
      BMI of >24 performed satisfactory CPR when using the recommended Resuscitation
      Council guidelines. Females with a BMI <24 performed CPR more effectively when
      using the 15:2 ratio. FY1 doctors should be fully assessed prior to performing
      CPR at in-hospital cardiac arrests. Remedial teaching should be given to those
      less than satisfactory until they are shown to be competent.

PMID- 23536734
TI  - Lumps, bumps and GI bleeding.
AB  - We report the case of a patient presenting with malaena and anaemia secondary to
      a metastatic phyllodes tumour of the breast. This is an unusual clinical
      presentation from a breast tumour that rarely metastasise.

PMID- 23536735
TI  - Acute respiratory distress syndrome caused by Mycoplasma pneumoniae diagnosed by
      polymerase chain reaction.
AB  - Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen in cases of atypical
      pneumonia. Most individuals with Mycoplasma pneumonia run a benign course, with
      non-specific symptoms of malaise, fever and non-productive cough that usually
      resolve with no long-term sequelae. Acute lung injury is not commonly seen in
      Mycoplasma pneumonia. We report a case of acute respiratory distress syndrome
      cause by M. pneumoniae diagnosed by quantitative real-time polymerase chain
      reaction (RT-PCR).

PMID- 23536736
TI  - What is the real function of the liver 'function' tests?
AB  - Liver enzymes are commonly used in the evaluation of patients with a range of
      diseases. Classically they are used to give information on whether a patient's
      primary disorder is hepatitic or cholestatic in origin. However, knowledge of
      enzyme ratios and pattern recognition allow much more information to be derived
      from these simple tests. This paper offers an insight to generalists on how to
      extractgreater information from these tests in order to improve theinvestigation
      and management of liver disease.

PMID- 23536737
TI  - The frustration of Lady Aberdeen in her crusade against tuberculosis in Ireland.
AB  - When in his Annual Report for 1905 the Registrar General for Ireland pointed out
      to the lately arrived Lord Lieutenant, The Earl of Aberdeen, that annually in
      every 100 deaths in Ireland 16 were victims of tuberculosis, Lady Aberdeen took
      notice. In March 1907 she founded the WNHA with the clear duty of taking part in
      the fight against the appalling ravages of that disease, and organised a
      Tuberculosis Exhibition the following October. And so began a campaign that led
      to the building of Peamount Sanatorium in county Dublin, the Allan Ryan Hospital
      at Ringsend, and the Collier Dispensary in the city centre. However, the Irish
      parliamentarians at Westminster emasculated the Tuberculosis Prevention (Ireland)
      Act 1908 by ensuring that notification was not made compulsory. Passage of the
      National Health Insurance Act (1911) necessitated changes that resulted in the
      Tuberculosis Prevention (Ireland) Act (1913), but the crucial shortcomings of the
      earlier Act were not rectified: notification was necessary but still not
      compulsory. Lady Aberdeen recognised this serious flaw she was powerless to
      correct, and turned to propaganda, editing Slainte, a monthly magazine founded in
      January 1909 by the WNHA, and editing a three-volume account of Ireland's Crusade
      Against Tuberculosis (1908-1909).

PMID- 23536738
TI  - What is the future of minor surgery in Northern Ireland.

PMID- 23536739
TI  - Are we providing the multimodality treatments advocated within current guidelines
      when managing patients with lower back pain?

PMID- 23536740
TI  - Home treatment: changes to mental healthcare in Northern Ireland.

PMID- 23536741
TI  - Perforation into the pericardial sac of an infant: a rare complication of central
      venous catheter insertion.

PMID- 23536742
TI  - Salivary Parameters of Competitive Swimmers at Gas-Chlorinated Swimming-Pools.

PMID- 23536743
TI  - Discrimination Skills Predict Effective Preference Assessment Methods for Adults
      with Developmental Disabilities.
AB  - We examined the relationship between three discrimination skills (visual, visual
      matching-to-sample, and auditory-visual) and four stimulus modalities (object,
      picture, spoken, and video) in assessing preferences of leisure activities for 7
      adults with developmental disabilities. Three discrimination skills were measured
      using the Assessment of Basic Learning Abilities Test. Three participants
      mastered a visual discrimination task, but not visual matching-to-sample and
      auditory-visual discriminations; two participants mastered visual and visual
      matching-to-sample discriminations, but not auditory-visual discrimination, and
      two participants showed all three discriminations. The most and least preferred
      activities, identified through paired-stimulus preference assessment using
      objects, were presented to each participant in each of the four modalities using
      a reversal design. The results showed that (1) participants with visual
      discrimination alone showed a preference for their preferred activities in the
      object modality only; (2) those with visual and visual matching-to-sample
      discriminations, but not auditory-visual discrimination, showed a preference for
      their preferred activities in the object but not in the spoken modality, and
      mixed results in the pictorial and video modalities; and (3) those with all three
      discriminations showed a preference for their preferred activities in all four
      modalities. These results provide partial replications of previous findings on
      the relationship between discriminations and object, pictorial, and spoken
      modalities, and extend previous research to include video stimuli.

PMID- 23536744
TI  - Integration of Self-Assembled Microvascular Networks with Microfabricated PEG
      Based Hydrogels.
AB  - Despite tremendous efforts, tissue engineered constructs are restricted to thin,
      simple tissues sustained only by diffusion. The most significant barrier in
      tissue engineering is insufficient vascularization to deliver nutrients and
      metabolites during development in vitro and to facilitate rapid vascular
      integration in vivo. Tissue engineered constructs can be greatly improved by
      developing perfusable microvascular networks in vitro in order to provide
      transport that mimics native vascular organization and function. Here a
      microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co
      culture in a strategy to perfuse microvascular networks in vitro. This approach
      allows for control over microvascular network self-assembly and employs an
      anastomotic interface for integration of self-assembled micro-vascular networks
      with fabricated microchannels. As a result, transport within the system shifts
      from simple diffusion to vessel supported convective transport and extra-vessel
      diffusion, thus improving overall mass transport properties. This work impacts
      the development of perfusable prevascularized tissues in vitro and ultimately
      tissue engineering applications in vivo.

PMID- 23536748
TI  - Changes in phlebotomine sand fly species composition following insecticide
      thermal fogging in a rural setting of Western panama.
AB  - American Cutaneous Leishmaniasis, ACL, is a zoonotic disease with a large
      richness of co-occurring vector species in transmission foci. Here, we describe
      changes in patterns of phlebotomine sand fly (Diptera: Psychodidae:
      Phlebotominae) species composition at the village of Trinidad de Las Minas,
      Capira, Panama, a hyperendemic focus of ACL transmission, subjected to a vector
      control intervention with insecticide thermal fogging (ITF). Our study setting
      consisted of 24 houses, 12 subjected to two rounds of ITF and 12 kept as control.
      During 15 months (April 2010- June 2011) we monitored sand fly species
      composition and abundance with modified HP light traps inside (domicile) and
      outside (peridomicile) the studied houses. From 5628 sand flies collected, we
      were able to identify 5617 of the samples into 24 species, a number of species
      close to 25+/-1.6, the estimate from the Chao2 Index. The most abundant species
      were Lutzomya trapidoi (20%), Lu. gomezi (20%) and Lu. triramula (20%). Cluster
      analyses showed that most of the 24 houses had high similarity in relative
      abundance patterns of the six most common species, with only few peripheral
      houses not following the main cluster pattern. We also found that species
      richness was decreased to 22 species in the fogged houses, of which only 19 were
      found in the domiciliary environment. Changes in species richness were especially
      notorious at the end of the wet season. Our results suggest that species richness
      can decrease following ITF in domiciliary environments, primarily affecting the
      less common species.

PMID- 23536749
TI  - The dynamic range paradox: a central auditory model of intensity change
      detection.
AB  - In this paper we use empirical loudness modeling to explore a perceptual sub
      category of the dynamic range problem of auditory neuroscience. Humans are able
      to reliably report perceived intensity (loudness), and discriminate fine
      intensity differences, over a very large dynamic range. It is usually assumed
      that loudness and intensity change detection operate upon the same neural signal,
      and that intensity change detection may be predicted from loudness data and vice
      versa. However, while loudness grows as intensity is increased, improvement in
      intensity discrimination performance does not follow the same trend and so
      dynamic range estimations of the underlying neural signal from loudness data
      contradict estimations based on intensity just-noticeable difference (JND) data.
      In order to account for this apparent paradox we draw on recent advances in
      auditory neuroscience. We test the hypothesis that a central model, featuring
      central adaptation to the mean loudness level and operating on the detection of
      maximum central-loudness rate of change, can account for the paradoxical data. We
      use numerical optimization to find adaptation parameters that fit data for
      continuous-pedestal intensity change detection over a wide dynamic range. The
      optimized model is tested on a selection of equivalent pseudo-continuous
      intensity change detection data. We also report a supplementary experiment which
      confirms the modeling assumption that the detection process may be modeled as
      rate-of-change. Data are obtained from a listening test (N = 10) using linearly
      ramped increment-decrement envelopes applied to pseudo-continuous noise with an
      overall level of 33 dB SPL. Increments with half-ramp durations between 5 and
      50,000 ms are used. The intensity JND is shown to increase towards long duration
      ramps (p<10(-6)). From the modeling, the following central adaptation parameters
      are derived; central dynamic range of 0.215 sones, 95% central normalization, and
      a central loudness JND constant of 5.5*10(-5) sones per ms. Through our findings,
      we argue that loudness reflects peripheral neural coding, and the intensity JND
      reflects central neural coding.

PMID- 23536754
TI  - Robustness and strategies of adaptation among farmer varieties of African Rice
      (Oryza glaberrima) and Asian Rice (Oryza sativa) across West Africa.
AB  - This study offers evidence of the robustness of farmer rice varieties (Oryza
      glaberrima and O. sativa) in West Africa. Our experiments in five West African
      countries showed that farmer varieties were tolerant of sub-optimal conditions,
      but employed a range of strategies to cope with stress. Varieties belonging to
      the species Oryza glaberrima - solely the product of farmer agency - were the
      most successful in adapting to a range of adverse conditions. Some of the farmer
      selections from within the indica and japonica subspecies of O. sativa also
      performed well in a range of conditions, but other farmer selections from within
      these two subspecies were mainly limited to more specific niches. The results
      contradict the rather common belief that farmer varieties are only of local
      value. Farmer varieties should be considered by breeding programmes and used
      (alongside improved varieties) in dissemination projects for rural food security.

PMID- 23536755
TI  - Behavioral and synaptic circuit features in a zebrafish model of fragile X
      syndrome.
AB  - Fragile X syndrome (FXS) is the most frequent inherited form of human mental
      retardation. It is characterized by cognitive impairment and physical and
      behavioral problems and is caused by the silencing of fmr1 transcription and the
      absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly
      facilitated the investigation of the molecular and cellular mechanisms of this
      loss-of-function disorder. The present study was aimed to further characterize
      the role of FMRP in behavior and synaptic function by using fmr1 knockout
      zebrafish. In adult zebrafish, we found that fmr1 knockout produces the
      anxiolytic-like responses of increased exploratory behavior in light/dark and
      open-field tests and avoidance learning impairment. Furthermore,
      electrophysiological recordings from telencephalic slice preparations of knockout
      fish displayed markedly reduced long-term potentiation and enhanced long-term
      depression compared to wild-type fish; however, basal glutamatergic transmission
      and presynaptic function at the lateral (Dl) and medial (Dm) division of the
      dorsal telencephalon synapse remained normal. Taken together, our study not only
      evaluates the mechanism of FRMP but also suggests that zebrafish have valuable
      potential as a complementary vertebrate model in studying the molecular
      pathogenesis of human fragile X syndrome.

PMID- 23536756
TI  - Vaccination to conserved influenza antigens in mice using a novel Simian
      adenovirus vector, PanAd3, derived from the bonobo Pan paniscus.
AB  - Among approximately 1000 adenoviruses from chimpanzees and bonobos studied
      recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan
      paniscus) has one of the best profiles for a vaccine vector, combining potent
      transgene immunogenicity with minimal pre-existing immunity in the human
      population. In this study, we inserted into a replication defective PanAd3 a
      transgene expressing a fusion protein of conserved influenza antigens
      nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell
      responses as well as protection from challenge infection in a mouse model. A
      single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody
      and T cell responses, and protected against high dose lethal influenza virus
      challenge. Thus PanAd3 is a promising candidate vector for vaccines, including
      universal influenza vaccines.

PMID- 23536758
TI  - Machine perfusion versus cold storage of kidneys derived from donation after
      cardiac death: a meta-analysis.
AB  - BACKGROUND: In response to the increased organ shortage, organs derived from
      donation after cardiac death (DCD) donors are becoming an acceptable option once
      again for clinical use in transplantation. However, transplant outcomes in cases
      where DCD organs are used are not as favorable as those from donation after brain
      death or living donors. Different methods of organ preservation are a key factor
      that may influence the outcomes of DCD kidney transplantation. METHODS: We
      compared the transplant outcomes in patients receiving DCD kidneys preserved by
      machine perfusion (MP) or by static cold storage (CS) preservation by conducting
      a meta-analysis. The MEDLINE, EMBASE and Cochrane Library databases were
      searched. All studies reporting outcomes for MP versus CS preserved DCD kidneys
      were further considered for inclusion in this meta-analysis. Odds ratios and 95%
      confidence intervals (CI) were calculated to compare the pooled data between
      groups that were transplanted with kidneys that were preserved by MP or CS.
      RESULTS: Four prospective, randomized, controlled trials, involving 175 MP and
      176 CS preserved DCD kidney transplant recipients, were included. MP preserved
      DCD kidney transplant recipients had a decreased incidence of delayed graft
      function (DGF) with an odd ration of 0.56 (95% CI = 0.36-0.86, P = 0.008)
      compared to CS. However, no significant differences were seen between the two
      technologies in incidence of primary non-function, one year graft survival, or
      one year patient survival. CONCLUSIONS: MP preservation of DCD kidneys is
      superior to CS in terms of reducing DGF rate post-transplant. However, primary
      non-function, one year graft survival, and one year patient survival were not
      affected by the use of MP or CS for preservation.

PMID- 23536757
TI  - Genetic and structure-function studies of missense mutations in human endothelial
      lipase.
AB  - Endothelial lipase (EL) plays a pivotal role in HDL metabolism. We sought to
      characterize EL and its interaction with HDL as well as its natural variants
      genetically, functionally and structurally. We screened our biethnic population
      sample (n = 802) for selected missense mutations (n = 5) and identified T111I as
      the only common variant. Multiple linear regression analyses in Hispanic subjects
      revealed an unexpected association between T111I and elevated LDL-C (p-value =
      0.012) and total cholesterol (p-value = 0.004). We examined lipase activity of
      selected missense mutants (n = 10) and found different impacts on EL function,
      ranging from normal to complete loss of activity. EL-HDL lipidomic analyses
      indicated that EL has a defined remodeling of HDL without exhaustion of the
      substrate and a distinct and preference for several fatty acids that are lipid
      mediators and known for their potent pro- and anti-inflammatory properties.
      Structural studies using homology modeling revealed a novel alpha/beta motif in
      the C-domain, unique to EL. The EL dimer was found to have the flexibility to
      expand and to bind various sizes of HDL particles. The likely impact of the all
      known missense mutations (n = 18) on the structure of EL was examined using
      molecular modeling and the impact they may have on EL lipase activity using a
      novel structure-function slope based on their structural free energy differences.
      The results of this multidisciplinary approach delineated the impact of EL and
      its variants on HDL. Moreover, the results suggested EL to have the capacity to
      modulate vascular health through its role in fatty acid-based signaling pathways.

PMID- 23536759
TI  - Among-population variation in microbial community structure in the floral nectar
      of the bee-pollinated forest herb Pulmonaria officinalis L.
AB  - BACKGROUND: Microbial communities in floral nectar have been shown to be
      characterized by low levels of species diversity, yet little is known about among
      plant population variation in microbial community composition.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated the microbial community structure
      (yeasts and bacteria) in floral nectar of ten fragmented populations of the bee
      pollinated forest herb Pulmonaria officinalis. We also explored possible
      relationships between plant population size and microbial diversity in nectar,
      and related microbial community composition to the distance separating plant
      populations. Culturable bacteria and yeasts occurring in the floral nectar of a
      total of 100 plant individuals were isolated and identified by partially
      sequencing the 16S rRNA gene and D1/D2 domains of the 26S rRNA gene,
      respectively. A total of 9 and 11 yeast and 28 and 39 bacterial OTUs was found,
      taking into account a 3% (OTU0.03) and 1% sequence dissimilarity cut-off
      (OTU0.01). OTU richness at the plant population level (i.e. the number of OTUs
      per population) was low for yeasts (mean: 1.7, range: 0-4 OTUs0.01/0.03 per
      population), whereas on average 6.9 (range: 2-13) OTUs0.03 and 7.9 (range 2-16)
      OTUs0.01 per population were found for bacteria. Both for yeasts and bacteria,
      OTU richness was not significantly related to plant population size. Similarity
      in community composition among populations was low (average Jaccard index: 0.14),
      and did not decline with increasing distance between populations.
      CONCLUSIONS/SIGNIFICANCE: We found low similarity in microbial community
      structure among populations, suggesting that the assembly of nectar microbiota is
      to a large extent context-dependent. Although the precise factors that affect
      variation in microbial community structure in floral nectar require further
      study, our results indicate that both local and regional processes may contribute
      to among-population variation in microbial community structure in nectar.

PMID- 23536760
TI  - The first symbiont-free genome sequence of marine red alga, Susabi-nori (Pyropia
      yezoensis).
AB  - Nori, a marine red alga, is one of the most profitable mariculture crops in the
      world. However, the biological properties of this macroalga are poorly understood
      at the molecular level. In this study, we determined the draft genome sequence of
      susabi-nori (Pyropia yezoensis) using next-generation sequencing platforms. For
      sequencing, thalli of P. yezoensis were washed to remove bacteria attached on the
      cell surface and enzymatically prepared as purified protoplasts. The assembled
      contig size of the P. yezoensis nuclear genome was approximately 43 megabases
      (Mb), which is an order of magnitude smaller than the previously estimated genome
      size. A total of 10,327 gene models were predicted and about 60% of the genes
      validated lack introns and the other genes have shorter introns compared to large
      genome algae, which is consistent with the compact size of the P. yezoensis
      genome. A sequence homology search showed that 3,611 genes (35%) are functionally
      unknown and only 2,069 gene groups are in common with those of the unicellular
      red alga, Cyanidioschyzon merolae. As color trait determinants of red algae,
      light-harvesting genes involved in the phycobilisome were predicted from the P.
      yezoensis nuclear genome. In particular, we found a second homolog of
      phycobilisome-degradation gene, which is usually chloroplast-encoded, possibly
      providing a novel target for color fading of susabi-nori in aquaculture. These
      findings shed light on unexplained features of macroalgal genes and genomes, and
      suggest that the genome of P. yezoensis is a promising model genome of marine red
      algae.

PMID- 23536761
TI  - Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal
      seizures.
AB  - Neonatal seizures can be refractory to conventional anticonvulsants, and this may
      in part be due to a developmental increase in expression of the neuronal Na(+)
      K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions
      of GABAA receptors in the perinatal period. The most common cause of neonatal
      seizures is hypoxic encephalopathy, and here we show in an established model of
      neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in
      combination with phenobarbital is significantly more effective than phenobarbital
      alone. A sensitive mass spectrometry assay revealed that bumetanide
      concentrations in serum and brain were dose-dependent, and the expression of
      NKCC1 protein transiently increased in cortex and hippocampus after hypoxic
      seizures. Importantly, the low doses of phenobarbital and bumetanide used in the
      study did not increase constitutive apoptosis, alone or in combination.
      Perforated patch clamp recordings from ex vivo hippocampal slices removed
      following seizures revealed that phenobarbital and bumetanide largely reversed
      seizure-induced changes in EGABA. Taken together, these data provide preclinical
      support for clinical trials of bumetanide in human neonates at risk for hypoxic
      encephalopathy and seizures.

PMID- 23536762
TI  - GADD45alpha induction by nickel negatively regulates JNKs/p38 activation via
      promoting PP2Calpha expression.
AB  - Growth arrest and DNA damage (GADD) 45alpha is a member of GADD inducible gene
      family, and is inducible in cell response to oxidative stress. GADD45alpha
      upregulation induces MKK4/JNK activation in some published experimental systems.
      However, we found here that the depletion of GADD45alpha (GADD45alpha-/-) in
      mouse embryonic fibroblasts (MEFs) resulted in an increase in the phosphorylation
      of MKK4/7, MKK3/6 and consequently specific up-regulated the activation of
      JNK/p38 and their downstream transcription factors, such as c-Jun and ATF2, in
      comparison to those in GADD45alpha+/+ MEFs cell following nickel exposure. This
      up-regulation of MKK-JNK/p38 pathway in GADD45alpha-/- cell could be rescued by
      the reconstitutional expression of HA-GADD45alpha in GADD45alpha-/- MEFs,
      GADD45alpha-/-(HA-GADD45alpha). Subsequent studies indicated that GADD45alpha
      deletion repressed expression of PP2Calpha, the phosphotase of MKK3/6 and MKK4/7,
      whereas ectopic expression of HA-PP2Calpha in GADD45alpha-/- cells attenuated
      activation of MKK3/6-p38 and MKK4/7-JNK pathways. Collectively, our results
      demonstrate a novel function and mechanism responsible for GADD45alpha regulation
      of MKK/MAPK pathway, further provides insight into understanding the big picture
      of GADD45alpha in the regulation of cellular responses to oxidative stress and
      environmental carcinogens.

PMID- 23536763
TI  - Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a key role in
      vasculogenic mimicry formation, neovascularization and tumor initiation by Glioma
      stem-like cells.
AB  - Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells
      (GSLCs). GSLCs also participate in tumor neovascularization by
      transdifferentiating into vascular endothelial cells. Here, we report a critical
      role of GSLCs in the formation of vasculogenic mimicry (VM), which defines
      channels lined by tumor cells to supply nutrients to early growing tumors and
      tumor initiation. GSLCs preferentially expressed vascular endothelial growth
      factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis,
      tubule formation and increased expression of critical VM markers by GSLCs.
      Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self
      renewal, forming tubules, initiating xenograft tumors, promoting vascularization
      and the establishment of VM. Our study demonstrates VEGFR-2 as an essential
      molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor
      vasculature, and direct initiation of tumor.

PMID- 23536764
TI  - A triad of highly divergent polymeric immunoglobulin receptor (PIGR) haplotypes
      with major effect on IgA concentration in bovine milk.
AB  - The aim of this study was to determine a genetic basis for IgA concentration in
      milk of Bos taurus. We used a Holstein-Friesian x Jersey F2 crossbred pedigree to
      undertake a genome-wide search for QTL influencing IgA concentration and yield in
      colostrum and milk. We identified a single genome-wide significant QTL on
      chromosome 16, maximising at 4.8 Mbp. The polymeric immunoglobulin receptor gene
      (PIGR) was within the confidence interval of the QTL. In addition, mRNA
      expression analysis revealed a liver PIGR expression QTL mapping to the same
      locus as the IgA quantitative trait locus. Sequencing and subsequent genotyping
      of the PIGR gene revealed three divergent haplotypes that explained the variance
      of both the IgA QTL and the PIGR expression QTL. Genetic selection based on these
      markers will facilitate the production of bovine herds producing milk with higher
      concentrations of IgA.

PMID- 23536765
TI  - Expression of Biliverdin Reductase A in peripheral blood leukocytes is associated
      with treatment response in HCV-infected patients.
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is associated with
      systemic oxidative stress. Since the heme catabolic pathway plays an important
      role in antioxidant protection, we attempted to assess the gene expression of key
      enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2),
      and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes
      (PBL) of patients chronically infected with HCV. METHODS: Gene expressions
      (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naive
      patients (n = 58) and controls (n = 55), with a subset of HCV patients having
      data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV
      patients were classified as either responders (n = 38) or treatment-failure
      patients (n = 20). Blood samples in HCV patients were collected at day 0, and
      week 12, 24, 36, and 48 after the initiation of standard antiviral therapy.
      RESULTS: Compared to the controls, substantially increased BLVRA expression was
      detected in PBL (p<0.001) of therapeutically naive HCV patients. mRNA levels of
      BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03).
      A marked difference in BLVRA expression in PBL between the sustained responders
      and patients with treatment failure was detected at week 0 and during the follow
      up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL
      was an independent predictor for sustained virological response (OR 15; 95% CI
      1.05-214.2; P = 0.046). HMOX1/2 expression did not have any effect on the
      treatment outcome. CONCLUSION: Our results suggest that patients with chronic HCV
      infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA
      overexpression is associated with non-responsiveness to standard antiviral
      therapy; whereas, HMOX1/2 does not seem to have any predictive potential.

PMID- 23536766
TI  - Pharmacometabolomics reveals racial differences in response to atenolol
      treatment.
AB  - Antihypertensive drugs are among the most commonly prescribed drugs for chronic
      disease worldwide. The response to antihypertensive drugs varies substantially
      between individuals and important factors such as race that contribute to this
      heterogeneity are poorly understood. In this study we use metabolomics, a global
      biochemical approach to investigate biochemical changes induced by the beta
      adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma
      from individuals treated with atenolol was collected at baseline (untreated) and
      after a 9 week treatment period and analyzed using a GC-TOF metabolomics
      platform. The metabolomic signature of atenolol exposure included saturated
      (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated
      (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after
      treatment but were not different in African Americans (p<0.0005, q<0.03).
      Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in
      Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans.
      The contribution of genetic variation in genes that encode lipases to the racial
      differences in atenolol-induced changes in fatty acids was examined. SNP
      rs9652472 in LIPC was found to be associated with the change in oleic acid in
      Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP
      rs7250148 associated with oleic acid change in African Americans (p<0.0001) but
      not Caucasians. Together, these data indicate that atenolol-induced changes in
      the metabolome are dependent on race and genotype. This study represents a first
      step of a pharmacometabolomic approach to phenotype patients with hypertension
      and gain mechanistic insights into racial variability in changes that occur with
      atenolol treatment, which may influence response to the drug.

PMID- 23536767
TI  - protective effect of tetracycline against dermal toxicity induced by Jellyfish
      venom.
AB  - BACKGROUND: Previously, we have reported that most, if not all, of the Scyphozoan
      jellyfish venoms contain multiple components of metalloproteinases, which
      apparently linked to the venom toxicity. Further, it is also well known that
      there is a positive correlation between the inflammatory reaction of dermal
      tissues and their tissue metalloproteinase activity. Based on these, the use of
      metalloproteinase inhibitors appears to be a promising therapeutic alternative
      for the treatment of jellyfish envenomation. METHODOLOGY AND PRINCIPAL FINDINGS:
      Tetracycline (a metalloproteinase inhibitor) has been examined for its activity
      to reduce or prevent the dermal toxicity induced by Nemopilema nomurai
      (Scyphozoa: Rhizostomeae) jellyfish venom (NnV) using in vitro and in vivo
      models. HaCaT (human keratinocyte) and NIH3T3 (mouse fibroblast) incubated with
      NnV showed decreases in cell viability, which is associated with the inductions
      of metalloproteinase-2 and -9. This result suggests that the use of
      metalloproteinase inhibitors, such as tetracycline, may prevent the jellyfish
      venom-mediated local tissue damage. In vivo experiments showed that comparing
      with NnV-alone treatment, tetracycline pre-mixed NnV demonstrated a significantly
      reduced progression of dermal toxicity upon the inoculation onto rabbit skin.
      CONCLUSIONS/SIGNIFICANCE: It is believed that there has been no previous report
      on the therapeutic agent of synthetic chemical origin for the treatment of
      jellyfish venom-induced dermonecrosis based on understanding its mechanism of
      action except the use of antivenom treatment. Furthermore, the current study, for
      the first time, has proposed a novel mechanism-based therapeutic intervention for
      skin damages caused by jellyfish stings.

PMID- 23536768
TI  - Ecto-nucleoside triphosphate diphosphohydrolase 2 modulates local ATP-induced
      calcium signaling in human HaCaT keratinocytes.
AB  - Keratinocytes are the major building blocks of the human epidermis. In many
      physiological and pathophysiological conditions, keratinocytes release adenosine
      triphosphate (ATP) as an autocrine/paracrine mediator that regulates cell
      proliferation, differentiation, and migration. ATP receptors have been identified
      in various epidermal cell types; therefore, extracellular ATP homeostasis likely
      determines its long-term, trophic effects on skin health. We investigated the
      possibility that human keratinocytes express surface-located enzymes that
      modulate ATP concentration, as well as the corresponding receptor activation, in
      the pericellular microenvironment. We observed that the human keratinocyte cell
      line HaCaT released ATP and hydrolyzed extracellular ATP. Interestingly, ATP
      hydrolysis resulted in adenosine diphosphate (ADP) accumulation in the
      extracellular space. Pharmacological inhibition by ARL 67156 or gene silencing of
      the endogenous ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) isoform
      2 resulted in a 25% reduction in both ATP hydrolysis and ADP formation. Using
      intracellular calcium as a reporter, we found that although NTPDase2 hydrolyzed
      ATP and generated sustainable ADP levels, only ATP contributed to increased
      intracellular calcium via P2Y2 receptor activation. Furthermore, knocking down
      NTPDase2 potentiated the nanomolar ATP-induced intracellular calcium increase,
      suggesting that NTPDase2 globally attenuates nucleotide concentration in the
      pericellular microenvironment as well as locally shields receptors in the
      vicinity from being activated by extracellular ATP. Our findings reveal an
      important role of human keratinocyte NTPDase2 in modulating nucleotide signaling
      in the extracellular milieu of human epidermis.

PMID- 23536769
TI  - Aerobic and combined exercise sessions reduce glucose variability in type 2
      diabetes: crossover randomized trial.
AB  - PURPOSE: To evaluate the effects of aerobic (AER) or aerobic plus resistance
      exercise (COMB) sessions on glucose levels and glucose variability in patients
      with type 2 diabetes. Additionally, we assessed conventional and non-conventional
      methods to analyze glucose variability derived from multiple measurements
      performed with continuous glucose monitoring system (CGMS). METHODS: Fourteen
      patients with type 2 diabetes (56+/-2 years) wore a CGMS during 3 days.
      Participants randomly performed AER and COMB sessions, both in the morning (24 h
      after CGMS placement), and at least 7 days apart. Glucose variability was
      evaluated by glucose standard deviation, glucose variance, mean amplitude of
      glycemic excursions (MAGE), and glucose coefficient of variation (conventional
      methods) as well as by spectral and symbolic analysis (non-conventional methods).
      RESULTS: Baseline fasting glycemia was 139+/-05 mg/dL and HbA1c 7.9+/-0.7%.
      Glucose levels decreased immediately after AER and COMB protocols by ~16%, which
      was sustained for approximately 3 hours. Comparing the two exercise modalities,
      responses over a 24-h period after the sessions were similar for glucose levels,
      glucose variance and glucose coefficient of variation. In the symbolic analysis,
      increases in 0 V pattern (COMB, 67.0+/-7.1 vs. 76.0+/-6.3, P = 0.003) and
      decreases in 1 V pattern (COMB, 29.1+/-5.3 vs. 21.5+/-5.1, P = 0.004) were
      observed only after the COMB session. CONCLUSIONS: Both AER and COMB exercise
      modalities reduce glucose levels similarly for a short period of time. The use of
      non-conventional analysis indicates reduction of glucose variability after a
      single session of combined exercises. TRIAL REGISTRATION: Aerobic training,
      aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS
      exercise). ClinicalTrials.gov ID: NCT00887094.

PMID- 23536770
TI  - Stem cell-like gene expression in ovarian cancer predicts type II subtype and
      prognosis.
AB  - Although ovarian cancer is often initially chemotherapy-sensitive, the vast
      majority of tumors eventually relapse and patients die of increasingly aggressive
      disease. Cancer stem cells are believed to have properties that allow them to
      survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer
      initiating cells are a rare cell population and difficult to isolate
      experimentally. Genes that are expressed by stem cells may characterize a subset
      of less differentiated tumors and aid in prognostic classification of ovarian
      cancer. The purpose of this study was the genomic identification and
      characterization of a subtype of ovarian cancer that has stem cell-like gene
      expression. Using human and mouse gene signatures of embryonic, adult, or cancer
      stem cells, we performed an unsupervised bipartition class discovery on
      expression profiles from 145 serous ovarian tumors to identify a stem-like and
      more differentiated subgroup. Subtypes were reproducible and were further
      characterized in four independent, heterogeneous ovarian cancer datasets. We
      identified a stem-like subtype characterized by a 51-gene signature, which is
      significantly enriched in tumors with properties of Type II ovarian cancer; high
      grade, serous tumors, and poor survival. Conversely, the differentiated tumors
      share properties with Type I, including lower grade and mixed histological
      subtypes. The stem cell-like signature was prognostic within high-stage serous
      ovarian cancer, classifying a small subset of high-stage tumors with better
      prognosis, in the differentiated subtype. In multivariate models that adjusted
      for common clinical factors (including grade, stage, age), the subtype
      classification was still a significant predictor of relapse. The prognostic stem
      like gene signature yields new insights into prognostic differences in ovarian
      cancer, provides a genomic context for defining Type I/II subtypes, and potential
      gene targets which following further validation may be valuable in the clinical
      management or treatment of ovarian cancer.

PMID- 23536771
TI  - Rapamycin reverses status epilepticus-induced memory deficits and dendritic
      damage.
AB  - Cognitive impairments are prominent sequelae of prolonged continuous seizures
      (status epilepticus; SE) in humans and animal models. While often associated with
      dendritic injury, the underlying mechanisms remain elusive. The mammalian target
      of rapamycin complex 1 (mTORC1) pathway is hyperactivated following SE. This
      pathway modulates learning and memory and is associated with regulation of
      neuronal, dendritic, and glial properties. Thus, in the present study we tested
      the hypothesis that SE-induced mTORC1 hyperactivation is a candidate mechanism
      underlying cognitive deficits and dendritic pathology seen following SE. We
      examined the effects of rapamycin, an mTORC1 inhibitor, on the early hippocampal
      dependent spatial learning and memory deficits associated with an episode of
      pilocarpine-induced SE. Rapamycin-treated SE rats performed significantly better
      than the vehicle-treated rats in two spatial memory tasks, the Morris water maze
      and the novel object recognition test. At the molecular level, we found that the
      SE-induced increase in mTORC1 signaling was localized in neurons and microglia.
      Rapamycin decreased the SE-induced mTOR activation and attenuated microgliosis
      which was mostly localized within the CA1 area. These findings paralleled a
      reversal of the SE-induced decreases in dendritic Map2 and ion channels levels as
      well as improved dendritic branching and spine density in area CA1 following
      rapamycin treatment. Taken together, these findings suggest that mTORC1
      hyperactivity contributes to early hippocampal-dependent spatial learning and
      memory deficits and dendritic dysregulation associated with SE.

PMID- 23536772
TI  - Urokinase plasminogen activator induces pro-fibrotic/m2 phenotype in murine
      cardiac macrophages.
AB  - OBJECTIVE: Inflammation and fibrosis are intertwined in multiple disease
      processes. We have previously found that over-expression of urokinase plasminogen
      activator in macrophages induces spontaneous macrophage accumulation and fibrosis
      specific to the heart in mice. Understanding the relationship between
      inflammation and fibrosis in the heart is critical to developing therapies for
      diverse myocardial diseases. Therefore, we sought to determine if uPA induces
      changes in macrophage function that promote cardiac collagen accumulation.
      METHODS AND RESULTS: We analyzed the effect of the uPA transgene on expression of
      pro-inflammatory (M1) and pro-fibrotic (M2) genes and proteins in hearts and
      isolated macrophages of uPA overexpressing mice. We found that although there was
      elevation of the pro-inflammatory cytokine IL-6 in hearts of transgenic mice, IL
      6 is not a major effector of uPA induced cardiac fibrosis. However, uPA
      expressing bone marrow-derived macrophages are polarized to express M2 genes in
      response to IL-4 stimulation, and these M2 genes are upregulated in uPA
      expressing macrophages following migration to the heart. In addition, while uPA
      expressing macrophages express a transcriptional profile that is seen in tumor
      associated macrophages, these macrophages promote collagen expression in cardiac
      but not embryonic fibroblasts. CONCLUSIONS: Urokinase plasminogen activator
      induces an M2/profibrotic phenotype in macrophages that is fully expressed after
      migration of macrophages into the heart. Understanding the mechanisms by which
      uPA modulates macrophage function may reveal insights into diverse pathologic
      processes.

PMID- 23536773
TI  - Molecules altering the intracellular thiol content modulate NF-kB and STAT-1/IRF
      1 signalling pathways and IL-12 p40 and IL-27 p28 production in murine
      macrophages.
AB  - BACKGROUND: The aim of this study was to investigate the molecular mechanisms
      involved in the production of Th1 cytokines, namely IL-12 and IL-27, when the
      intra-macrophage redox state was altered by different chemical entities such as
      GSH-C4, which is reduced glutathione carrying an aliphatic chain, or I-152, a pro
      drug of N-acetyl-cysteine (NAC) and beta-mercaptoethylamine. We had already
      demonstrated that GSH-C4 and I-152 could shift the immune response towards Th1 in
      Ovalbumin-immunized mice as well as enhance Th1 response in HIV-1 Tat-immunized
      mice. METHODOLOGY/PRINCIPAL FINDINGS: By a new high performance liquid
      chromatography method, we found that 20 mM GSH-C4 provided a number of thiol
      species in the form of GSH, while 20 mM I-152 decreased GSH and increased the
      thiols in the form of NAC and I-152. Under these experimental conditions, GSH-C4
      and I-152 enhanced and suppressed respectively the mRNA expression levels of IL
      12 p40 induced by LPS/IFN-gamma as assessed by Real-Time PCR. The protein
      production of IL-12 p40 was increased by GSH-C4 and decreased by I-152 as
      determined by Enzyme-linked immunosorbent assay. Western immunoblot and
      electrophoretic mobility shift assays revealed that Nuclear Factor -kB (NF-kB)
      activation was inhibited by I-152 and prolonged by GSH-C4. Twenty mM I-152
      stimulated IL-27 p28 gene expression and sustained Signal Transducer and
      Activator of Transcription (STAT)-mediated interferon regulator factor 1 (IRF-1)
      de novo synthesis. By contrast, 20 mM GSH-C4 did not exert any effect on IL-27
      p28 gene expression. CONCLUSIONS AND SIGNIFICANCE: an increase in the intra
      macrophage redox state by GSH-C4 and I-152 enhances Th1 cytokine production
      although the chemical structure and the intra-cellular metabolism influence
      differently signalling pathways involved in IL-27 or IL-12 production. GSH-C4 and
      I-152 may be used as Th1 immunomodulators in some pathologies and in ageing where
      GSH depletion may contribute to the Th1/Th2 imbalance, and in new immunization
      strategies.

PMID- 23536774
TI  - Relationships among facial mimicry, emotional experience, and emotion
      recognition.
AB  - BACKGROUND: The relationships between facial mimicry and subsequent psychological
      processes remain unclear. We hypothesized that the congruent facial muscle
      activity would elicit emotional experiences and that the experienced emotion
      would induce emotion recognition. METHODOLOGY/PRINCIPAL FINDINGS: To test this
      hypothesis, we re-analyzed data collected in two previous studies. We recorded
      facial electromyography (EMG) from the corrugator supercilii and zygomatic major
      and obtained ratings on scales of valence and arousal for experienced emotions
      (Study 1) and for experienced and recognized emotions (Study 2) while
      participants viewed dynamic and static facial expressions of negative and
      positive emotions. Path analyses showed that the facial EMG activity consistently
      predicted the valence ratings for the emotions experienced in response to dynamic
      facial expressions. The experienced valence ratings in turn predicted the
      recognized valence ratings in Study 2. CONCLUSION: These results suggest that
      facial mimicry influences the sharing and recognition of emotional valence in
      response to others' dynamic facial expressions.

PMID- 23536775
TI  - A novel estimation of the relative economic value in terms of different chronic
      hepatitis B treatment options.
AB  - BACKGROUND: Prescribers, payors and healthcare decision-makers are increasingly
      examining the value of treatments. This study aims at analyzing economic value of
      chronic hepatitis B (CHB) treatment options, which are available in Korea.
      METHODS: CHB infection was simulated using a health-state transition model with
      disease states defined as mild disease (Ishak F0/F1), fibrosis (F2/F3/F4),
      advanced fibrosis/cirrhosis (>F4), and complicated disease states (decompensated
      cirrhosis, hepatocellular carcinoma, liver transplant and death) based on
      available natural history data. The value of treatment-specific attributes on
      disease progression/regression was estimated based on published data in terms of
      events and costs avoided. 5-year treatment duration was assumed except for
      treatment initiation. Primary model output is the estimated cost savings of
      entecavir per patient per day of treatment versus the comparator in question for
      a given CHB patient. RESULTS: The simulation of treating with entecavir versus no
      treatment predicted improved clinical outcomes for entecavir-treatment patients.
      In the long term, these clinical benefits translate into cost savings of $3.10
      per day of treatment. In naive patient treatment, daily cost savings of using
      entecavir versus lamivudine or telbivudine was estimated at $2.89 and $1.72,
      respectively. In the case of suboptimal responders who pre-treated with
      lamivudine, daily cost saving for patients switching to entecavir was $1.38 per
      day of treatment compared to patients maintaining on lamivudine. CONCLUSIONS:
      Entecavir exhibits characteristics of a favourable CHB treatment, which directly
      translates into economic and therapeutic value as opposed to either no treatment
      or alternative strategies.

PMID- 23536777
TI  - A method of neighbor classes based SVM classification for optical printed Chinese
      character recognition.
AB  - In optical printed Chinese character recognition (OPCCR), many classifiers have
      been proposed for the recognition. Among the classifiers, support vector machine
      (SVM) might be the best classifier. However, SVM is a classifier for two classes.
      When it is used for multi-classes in OPCCR, its computation is time-consuming.
      Thus, we propose a neighbor classes based SVM (NC-SVM) to reduce the computation
      consumption of SVM. Experiments of NC-SVM classification for OPCCR have been
      done. The results of the experiments have shown that the NC-SVM we proposed can
      effectively reduce the computation time in OPCCR.

PMID- 23536776
TI  - Molecular profiling of multiple human cancers defines an inflammatory cancer
      associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic
      cancer marker.
AB  - BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer.
      Inflammatory responses to cancer can also contribute directly to oncogenesis.
      Since the immune system is hardwired to protect the host, there is a possibility
      that cancers, regardless of their histological origins, endow themselves with a
      common and shared inflammatory cancer-associated molecular pattern (iCAMP) to
      promote oncoinflammation. However, the definition of iCAMP has not been
      conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide
      cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7
      cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A
      total of 96 inflammatory genes with consistent dysregulation were identified,
      including 44 up-regulated and 52 down-regulated genes. Protein expression was
      confirmed by immunohistochemistry for some of these genes. The iCAMP contains
      proteins whose roles in cancer have been implicated and others which are yet to
      be appreciated. The clinical significance of many iCAMP genes was confirmed in
      multiple independent cohorts of colon and ovarian cancer patients. In both cases,
      better prognosis correlated strongly with high CXCL13 and low level of GREM1,
      LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was
      further developed from the combination of 18 iCAMP genes in ovarian cancer, which
      predicted overall survival. Noticeably, as a selective nuclear import protein
      whose immuno-regulatory function just begins to emerge, karyopherin alpha 2
      (KPNA2) is uniformly up-regulated across cancer types. For the first time, the
      cancer-specific up-regulation of KPNA2 and its clinical significance were
      verified by tissue microarray analysis in colon and head-neck cancers.
      CONCLUSION: This work defines an inflammatory signature shared by seven
      epithelial cancer types and KPNA2 as a consistently up-regulated protein in
      cancer. Identification of iCAMP may not only serve as a novel biomarker for
      prognostication and individualized treatment of cancer, but also have significant
      biological implications.

PMID- 23536778
TI  - Loss of the keratin cytoskeleton is not sufficient to induce epithelial
      mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
AB  - Epithelial-to-mesenchymal transition (EMT), the phenotypical change of cells from
      an epithelial to a mesenchymal type, is thought to be a key event in invasion and
      metastasis of adenocarcinomas. These changes involve loss of keratin expression
      as well as loss of cell polarity and adhesion. We here aimed to determine whether
      the loss of keratin expression itself drives increased invasion and metastasis in
      adenocarcinomas and whether keratin loss leads to the phenotypic changes
      associated with EMT. Therefore, we employed a recently described murine model in
      which conditional deletion of the Keratin cluster II by Cre-recombinase leads to
      the loss of the entire keratinmultiprotein family. These mice were crossed into a
      newly generated Cre-recombinase inducible KRAS-driven murine lung cancer model to
      examine the effect of keratin loss on morphology, invasion and metastasis as well
      as expression of EMT related genes in the resulting tumors. We here clearly show
      that loss of a functional keratin cytoskeleton did not significantly alter tumor
      morphology or biology in terms of invasion, metastasis, proliferation or tumor
      burden and did not lead to induction of EMT. Further, tumor cells did not induce
      synchronously expression of vimentin, which is often seen in EMT, to compensate
      for keratin loss. In summary, our data suggest that changes in cell shape and
      migration that underlie EMT are dependent on changes in signaling pathways that
      cause secondary changes in keratin expression and organization. Thus, we conclude
      that loss of the keratin cytoskeleton per se is not sufficient to causally drive
      EMT in this tumor model.

PMID- 23536779
TI  - Does large needle aspiration biopsy add pain to the thyroid nodule evaluation?
AB  - Thyroid large needle aspiration biopsy is disregarded because it is thought to be
      associated with pain. This is in contrast with our 32 years long experience. We
      surveyed reports of pain in patients examined with fine needle aspiration biopsy
      (78, 87.2% women, mean age 59 years) or FNAB+large needle aspiration biopsy (48,
      87.5% women, mean age 60 years). Each patient was questioned regarding a) no
      unpleasant sensation (score "0"); b) unpleasant sensation ("1"); c) mild pain (no
      analgesic used; "2"); or d) pain (analgesic used; "3"). The mean size of the
      needle used was for FNAB 22.3+/-0.7 or 20.8+/-1 gauge in the fine needle
      aspiration or fine needle aspiration plus large needle aspiration biopsy group,
      respectively (p<.0001). The number of percutaneous punctures was higher in the
      fine needle aspiration plus large needle aspiration biopsy group. However, the
      pain score in the fine needle aspiration biopsy or fine needle aspiration biopsy
      plus large needle aspiration biopsy group was not significantly different. Large
      needle aspiration biopsy after fine needle aspiration biopsy does not add any
      discomfort or pain and therefore in light of the demonstrable benefits, should be
      included in clinical algorithms for the evaluation of thyroid nodules.

PMID- 23536780
TI  - A novel and major quantitative trait locus for fusarium crown rot resistance in a
      genotype of Wild Barley (Hordeum spontaneum L.).
AB  - Fusarium crown rot (FCR), caused by various Fusarium species, is a destructive
      disease of cereal crops in semiarid regions worldwide. As part of our
      contribution to the development of Fusarium resistant cultivars, we identified
      several novel sources of resistance by systematically assessing barley genotypes
      representing different geographical origins and plant types. One of these sources
      of resistance was investigated in this study by generating and analysing two
      populations of recombinant inbred lines. A major locus conferring FCR resistance,
      designated as Qcrs.cpi-4H, was detected in one of the populations (mapping
      population) and the effects of the QTL was confirmed in the other population. The
      QTL was mapped to the distal end of chromosome arm 4HL and it is effective
      against both of the Fusarium isolates tested, one F. pseudograminearum and the
      other F. graminearum. The QTL explains up to 45.3% of the phenotypic variance. As
      distinct from an earlier report which demonstrated co-locations of loci
      conferring FCR resistance and plant height in barley, a correlation between these
      two traits was not detected in the mapping population. However, as observed in a
      screen of random genotypes, an association between FCR resistance and plant
      growth rate was detected and a QTL controlling the latter was detected near the
      Qcrs.cpi-4H locus in the mapping population. Existing data indicate that,
      although growth rate may affect FCR resistance, different genes at this locus are
      likely involved in controlling these two traits.

PMID- 23536781
TI  - MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29
      case-control and TDT studies.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme
      for folate metabolism in humans; it is encoded by the MTHFR gene. Several studies
      have assessed the association between MTHFR C677T polymorphism and the risk of
      congenital heart defects (CHDs), while the results were inconsistent. METHODS AND
      FINDINGS: Multiple electronic databases were searched to identify relevant
      studies published up to July 22, 2012. Data from case-control and TDT studies
      were integrated in an allelic model using the Catmap and Metafor software. Twenty
      nine publications were included in this meta-analysis. The overall meta-analysis
      showed significant association between MTHFR C677T polymorphism and CHDs risk in
      children with heterogeneity (P heterogeneity = 0.000) and publication bias (P
      egger = 0.039), but it turned into null after the trim-and-fill method was
      implemented (OR = 1.12, 95% CI = 0.95-1.31). Nevertheless, positive results were
      obtained after stratified by ethnicity and sample size in all subgroups except
      the mixed population. For mothers, there was significant association between the
      variant and CHDs without heterogeneity (P heterogeneity = 0.150, OR = 1.16, 95%
      CI = 1.05-1.29) and publication bias (P egger = 0.981). However, the results
      varied across each subgroup in the stratified analysis of ethnicity and sample
      size. CONCLUSIONS: Both infant and maternal MTHFR C677T polymorphisms may
      contribute to the risk of CHDs.

PMID- 23536782
TI  - Non-invasive detection of coronary endothelial response to sequential handgrip
      exercise in coronary artery disease patients and healthy adults.
AB  - OBJECTIVES: Our objective is to test the hypothesis that coronary endothelial
      function (CorEndoFx) does not change with repeated isometric handgrip (IHG)
      stress in CAD patients or healthy subjects. BACKGROUND: Coronary responses to
      endothelial-dependent stressors are important measures of vascular risk that can
      change in response to environmental stimuli or pharmacologic interventions. The
      evaluation of the effect of an acute intervention on endothelial response is only
      valid if the measurement does not change significantly in the short term under
      normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two
      coronary artery endothelial function measurements separated by a ten minute
      interval in healthy subjects and patients with coronary artery disease (CAD).
      METHODS: Twenty healthy adult subjects and 12 CAD patients were studied on a
      commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area
      (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were
      quantified before and during continuous IHG stress, an endothelial-dependent
      stressor. The IHG exercise with imaging was repeated after a 10 minute recovery
      period. RESULTS: In healthy adults, coronary artery CSA changes and blood-flow
      increases did not differ between the first and second stresses (mean % change +/
      SEM, first vs. second stress CSA: 14.8%+/-3.3% vs. 17.8%+/-3.6%, p = 0.24; PDFV:
      27.5%+/-4.9% vs. 24.2%+/-4.5%, p = 0.54; blood-flow: 44.3%+/-8.3 vs. 44.8%+/-8.1,
      p = 0.84). The coronary vasoreactive responses in the CAD patients also did not
      differ between the first and second stresses (mean % change +/-SEM, first stress
      vs. second stress: CSA: -6.4%+/-2.0% vs. -5.0%+/-2.4%, p = 0.22; PDFV: -4.0%+/
      4.6% vs. -4.2%+/-5.3%, p = 0.83; blood-flow: -9.7%+/-5.1% vs. -8.7%+/-6.3%, p =
      0.38). CONCLUSION: MRI measures of CorEndoFx are unchanged during repeated
      isometric handgrip exercise tests in CAD patients and healthy adults. These
      findings demonstrate the repeatability of noninvasive 3T MRI assessment of
      CorEndoFx and support its use in future studies designed to determine the effects
      of acute interventions on coronary vasoreactivity.

PMID- 23536783
TI  - Fluid-phase pinocytosis of native low density lipoprotein promotes murine M-CSF
      differentiated macrophage foam cell formation.
AB  - During atherosclerosis, low-density lipoprotein (LDL)-derived cholesterol
      accumulates in macrophages to form foam cells. Macrophage uptake of LDL promotes
      foam cell formation but the mechanism mediating this process is not clear. The
      present study investigates the mechanism of LDL uptake for macrophage colony
      stimulating factor (M-CSF)-differentiated murine bone marrow-derived macrophages.
      LDL receptor-null (LDLR-/-) macrophages incubated with LDL showed non-saturable
      accumulation of cholesterol that did not down-regulate for the 24 h examined.
      Incubation of LDLR-/- macrophages with increasing concentrations of (125)I-LDL
      showed non-saturable macrophage LDL uptake. A 20-fold excess of unlabeled LDL had
      no effect on (125)I-LDL uptake by wild-type macrophages and genetic deletion of
      the macrophage scavenger receptors CD36 and SRA did not affect (125)I-LDL uptake,
      showing that LDL uptake occurred by fluid-phase pinocytosis independently of
      receptors. Cholesterol accumulation was inhibited approximately 50% in wild-type
      and LDLR-/- mice treated with LY294002 or wortmannin, inhibitors of all classes
      of phosphoinositide 3-kinases (PI3K). Time-lapse, phase-contrast microscopy
      showed that macropinocytosis, an important fluid-phase uptake pathway in
      macrophages, was blocked almost completely by PI3K inhibition with wortmannin.
      Pharmacological inhibition of the class I PI3K isoforms alpha, beta, gamma or
      delta did not affect macrophage LDL-derived cholesterol accumulation or
      macropinocytosis. Furthermore, macrophages from mice expressing kinase-dead class
      I PI3K beta, gamma or delta isoforms showed no decrease in cholesterol
      accumulation or macropinocytosis when compared with wild-type macrophages. Thus,
      non-class I PI3K isoforms mediated macropinocytosis in these macrophages. Further
      characterization of the components necessary for LDL uptake, cholesterol
      accumulation, and macropinocytosis identified dynamin, microtubules, actin, and
      vacuolar type H(+)-ATPase as contributing to uptake. However, Pak1, Rac1, and Src
      family kinases, which mediate fluid-phase pinocytosis in certain other cell
      types, were unnecessary. In conclusion, our findings provide evidence that
      targeting those components mediating macrophage macropinocytosis with inhibitors
      may be an effective strategy to limit macrophage accumulation of LDL-derived
      cholesterol in arteries.

PMID- 23536784
TI  - A novel 3D fibril force assay implicates src in tumor cell force generation in
      collagen networks.
AB  - New insight into the biomechanics of cancer cell motility in 3D extracellular
      matrix (ECM) environments would significantly enhance our understanding of
      aggressive cancers and help identify new targets for intervention. While several
      methods for measuring the forces involved in cell-matrix interactions have been
      developed, previous to this study none have been able to measure forces in a
      fibrillar environment. We have developed a novel assay for simultaneously
      measuring cell mechanotransduction and motility in 3D fibrillar environments. The
      assay consists of a controlled-density fibrillar collagen gel atop a controlled
      stiffness polyacrylamide (PAA) surface. Forces generated by living cells and
      their migration in the 3D collagen gel were measured with the 3D motion of tracer
      beads within the PAA layer. Here, this 3D fibril force assay is used to study the
      role of the invasion-associated protein kinase Src in mechanotransduction and
      motility. Src expression and activation are linked with proliferation, invasion,
      and metastasis, and have been shown to be required in 2D for invadopodia
      membranes to direct and mediate invasion. Breast cancer cell line MDA-MD-231 was
      stably transfected with GFP-tagged constitutively active Src or wild-type Src. In
      3D fibrillar collagen matrices we found that, relative to wild-type Src,
      constitutively active Src: 1) increased the strength of cell-induced forces on
      the ECM, 2) did not significantly change migration speed, and 3) increased both
      the duration and the length, but not the number, of long membrane protrusions.
      Taken together, these results support the hypothesis that Src controls invasion
      by controlling the ability of the cell to form long lasting cellular protrusions
      to enable penetration through tissue barriers, in addition to its role in
      promoting invadopodia matrix-degrading activity.

PMID- 23536785
TI  - In search of the trauma memory: a meta-analysis of functional neuroimaging
      studies of symptom provocation in posttraumatic stress disorder (PTSD).
AB  - Notwithstanding some discrepancy between results from neuroimaging studies of
      symptom provocation in posttraumatic stress disorder (PTSD), there is broad
      agreement as to the neural circuit underlying this disorder. It is thought to be
      characterized by an exaggerated amygdalar and decreased medial prefrontal
      activation to which the elevated anxiety state and concomitant inadequate
      emotional regulation are attributed. However, the proposed circuit falls short of
      accounting for the main symptom, unique among anxiety disorders to PTSD, namely,
      reexperiencing the precipitating event in the form of recurrent, distressing
      images and recollections. Owing to the technical demands, neuroimaging studies
      are usually carried out with small sample sizes. A meta-analysis of their
      findings is more likely to cast light on the involved cortical areas. Coordinate
      based meta-analyses employing ES-SDM (Effect Size Signed Differential Mapping)
      were carried out on 19 studies with 274 PTSD patients. Thirteen of the studies
      included 145 trauma-exposed control participants. Comparisons between reactions
      to trauma-related stimuli and a control condition and group comparison of
      reactions to the trauma-related stimuli were submitted to meta-analysis. Compared
      to controls and the neutral condition, PTSD patients showed significant
      activation of the mid-line retrosplenial cortex and precuneus in response to
      trauma-related stimuli. These midline areas have been implicated in self
      referential processing and salient autobiographical memory. PTSD patients also
      evidenced hyperactivation of the pregenual/anterior cingulate gyrus and bilateral
      amygdala to trauma-relevant, compared to neutral, stimuli. Patients showed
      significantly less activation than controls in sensory association areas such as
      the bilateral temporal gyri and extrastriate area which may indicate that the
      patients' attention was diverted from the presented stimuli by being focused on
      the elicited trauma memory. Being involved in associative learning and priming,
      the retrosplenial cortex may have an important function in relation to trauma
      memory, in particular, the intrusive reexperiencing of the traumatic event.

PMID- 23536786
TI  - Characterization and quantification of intact 26S proteasome proteins by real
      time measurement of intrinsic fluorescence prior to top-down mass spectrometry.
AB  - Quantification of gas-phase intact protein ions by mass spectrometry (MS) is
      impeded by highly-variable ionization, ion transmission, and ion detection
      efficiencies. Therefore, quantification of proteins using MS-associated
      techniques is almost exclusively done after proteolysis where peptides serve as
      proxies for estimating protein abundance. Advances in instrumentation, protein
      separations, and informatics have made large-scale sequencing of intact proteins
      using top-down proteomics accessible to the proteomics community; yet
      quantification of proteins using a top-down workflow has largely been
      unaddressed. Here we describe a label-free approach to determine the abundance of
      intact proteins separated by nanoflow liquid chromatography prior to MS analysis
      by using solution-phase measurements of ultraviolet light-induced intrinsic
      fluorescence (UV-IF). UV-IF is measured directly at the electrospray interface
      just prior to the capillary exit where proteins containing at least one
      tryptophan residue are readily detected. UV-IF quantification was demonstrated
      using commercially available protein standards and provided more accurate and
      precise protein quantification than MS ion current. We evaluated the parallel use
      of UV-IF and top-down tandem MS for quantification and identification of protein
      subunits and associated proteins from an affinity-purified 26S proteasome sample
      from Arabidopsis thaliana. We identified 26 unique proteins and quantified 13
      tryptophan-containing species. Our analyses discovered previously unidentified N
      terminal processing of the beta6 (PBF1) and beta7 (PBG1) subunit - such
      processing of PBG1 may generate a heretofore unknown additional protease active
      site upon cleavage. In addition, our approach permitted the unambiguous
      identification and quantification both isoforms of the proteasome-associated
      protein DSS1.

PMID- 23536787
TI  - Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer
      cases.
AB  - Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18%
      of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to
      50%. A variable incidence of mutations has been reported for these genes in
      ovarian cancer cases from different populations. In Greece, six mutations in
      BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes.
      This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort
      of 106 familial ovarian cancer patients that had strong family history or
      metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698
      patients were screened for the six recurrent Greek mutations (including founder
      mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23
      24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for
      exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in
      43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases.
      The variant of unknown clinical significance p.V1833M was identified in 9/698
      patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade
      serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or
      ovarian cancer families is important, as it enables carriers to take preventive
      measures. All ovarian cancer patients with a serous phenotype should be
      considered for genetic testing. Further studies are warranted to determine the
      prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and
      other novel predisposing genes for breast and ovarian cancer.

PMID- 23536788
TI  - Effect of feeding selenium-fertilized alfalfa hay on performance of weaned beef
      calves.
AB  - Selenium (Se) is an essential micronutrient in cattle, and Se-deficiency can
      affect morbidity and mortality. Calves may have greater Se requirements during
      periods of stress, such as during the transitional period between weaning and
      movement to a feedlot. Previously, we showed that feeding Se-fertilized forage
      increases whole-blood (WB) Se concentrations in mature beef cows. Our current
      objective was to test whether feeding Se-fertilized forage increases WB-Se
      concentrations and performance in weaned beef calves. Recently weaned beef calves
      (n = 60) were blocked by body weight, randomly assigned to 4 groups, and fed an
      alfalfa hay based diet for 7 wk, which was harvested from fields fertilized with
      sodium-selenate at a rate of 0, 22.5, 45.0, or 89.9 g Se/ha. Blood samples were
      collected weekly and analyzed for WB-Se concentrations. Body weight and health
      status of calves were monitored during the 7-wk feeding trial. Increasing
      application rates of Se fertilizer resulted in increased alfalfa hay Se content
      for that cutting of alfalfa (0.07, 0.95, 1.55, 3.26 mg Se/kg dry matter for Se
      application rates of 0, 22.5, 45.0, or 89.9 g Se/ha, respectively). Feeding Se
      fertilized alfalfa hay during the 7-wk preconditioning period increased WB-Se
      concentrations (P Linear<0.001) and body weights (P Linear = 0.002) depending
      upon the Se-application rate. Based upon our results we suggest that soil-Se
      fertilization is a potential management tool to improve Se-status and performance
      in weaned calves in areas with low soil-Se concentrations.

PMID- 23536790
TI  - Cost-effectiveness of long-lasting insecticide-treated hammocks in preventing
      malaria in South-central Vietnam.
AB  - BACKGROUND: Despite much success in reducing the burden of malaria in Vietnam,
      pockets of malaria persist and eliminating them remains an important development
      goal. In central Vietnam, insecticide-treated hammocks have recently been
      introduced to help counter the disease in the highly forested, mountainous areas,
      where other measures have so far been unsuccessful. This study assesses the cost
      effectiveness of using long-lasting insecticide-treated hammocks in this area.
      METHODS AND FINDINGS: This cost-effectiveness study was run alongside a
      randomized control trial testing the efficacy of the long-lasting insecticide
      treated hammocks. Data were collected through an exit survey, a household survey,
      expenditure records and key informant interviews. The study estimates that under
      normal (non-trial) conditions the total net societal cost per malaria episode
      averted in using long-lasting insecticide-treated hammocks in this area was 126
      USD. Cost per hammock, including insecticidal netting, sewing, transport, and
      distribution was found to be approximately 11.76 USD per hammock. Average savings
      per episode averted were estimated to be $14.60 USD for the health system and
      14.37 USD for households (including both direct and indirect cost savings). The
      study estimates that the annual financial outlay required of government to
      implement this type of programme to be 3.40 USD per person covered per year.
      CONCLUSION: The study finds that the use of a hammock intervention could
      represent good value for money to help prevent malaria in more remote areas,
      where traditional control measures such as insecticide-treated bednets and indoor
      residual spraying are insufficient or inappropriate to control malaria. However,
      the life span of the hammock-the number of years over which it effectively deters
      mosquitoes-has a significant impact on the cost-effectiveness of the intervention
      and study results should be interpreted in light of the evidence on effectiveness
      gathered in the years to come.

PMID- 23536789
TI  - Prevalence and incidence of latent tuberculosis infection in georgian healthcare
      workers.
AB  - BACKGROUND: Tuberculosis is a major occupational hazard in low and middle-income
      countries. Limited data exist on serial testing of healthcare workers (HCWs) with
      interferon-gamma release assays (IGRAs) for latent tuberculosis infection (LTBI),
      especially in low and middle-income countries. We sought to evaluate the rates of
      and risk factors for LTBI prevalence and LTBI test conversion among HCWs using
      the tuberculin skin test (TST) and QuantiFERON-TB Gold In-tube assay (QFT-GIT).
      METHODS: A prospective longitudinal study was conducted among HCWs in the country
      of Georgia. Subjects completed a questionnaire, and TST and QFT-GIT tests were
      performed. LTBI testing was repeated 6-26 months after baseline testing. RESULTS:
      Among 319 HCWs enrolled, 89% reported prior BCG vaccination, and 60% worked in TB
      healthcare facilities (HCFs). HCWs from TB HCFs had higher prevalence of positive
      QFT-GIT and TST than those from non-TB HCFs: 107/194 (55%) vs. 30/125 (31%) QFT
      GIT positive (p<0.0001) and 128/189 (69%) vs. 64/119 (54%) TST positive (p =
      0.01). There was fair agreement between TST and QFT-GIT (kappa = 0.42, 95% CI
      0.31-0.52). In multivariate analysis, frequent contact with TB patients was
      associated with increased risk of positive QFT-GIT (aOR 3.04, 95% CI 1.79-5.14)
      but not positive TST. Increasing age was associated with increased risk of
      positive QFT-GIT (aOR 1.05, 95% CI 1.01-1.09) and TST (aOR 1.05, 95% CI 1.01
      1.10). High rates of HCW conversion were seen: the QFT-GIT conversion rate was
      22.8/100 person-years, and TST conversion rate was 17.1/100 person-years. In
      multivariate analysis, female HCWs had decreased risk of TST conversion (aOR
      0.05, 95% CI 0.01-0.43), and older HCWs had increased risk of QFT-GIT conversion
      (aOR 1.07 per year, 95% CI 1.01-1.13). CONCLUSION: LTBI prevalence and LTBI test
      conversion rates were high among Georgian HCWs, especially among those working at
      TB HCFs. These data highlight the need for increased implementation of TB
      infection control measures.

PMID- 23536791
TI  - Polypyrimidine tract-binding protein induces p19(Ink4d) expression and inhibits
      the proliferation of H1299 cells.
AB  - The expression of polypyrimidine tract-binding protein (PTB) is up-regulated in
      many types of cancer. Here, we studied the role of PTB in the growth of non small
      cell lung cancer cells. Data showed that PTB overexpression inhibited the growth
      of H1299 cells at least by inhibiting DNA synthesis. Quantitative real-time PCR
      and Western blot analyses showed that PTB overexpression in H1299 cells
      specifically induced the expression of p19(Ink4d), an inhibitor of cyclin
      dependent kinase 4. Repression of p19(Ink4d) expression partially rescued PTB
      caused proliferation inhibition. PTB overexpression also inhibited the growth and
      induced the expression of p19(Ink4d) mRNA in A549 cells. However, Western blot
      analyses failed to detect the presence of p19(Ink4d) protein in A549 cells. To
      address how PTB induced p19(Ink4d) in H1299 cells, we showed that PTB might up
      regulate the activity of p19(Ink4d) gene (CDKN2D) promoter. Besides, PTB lacking
      the RNA recognition motif 3 (RRM3) was less effective in growth inhibition and
      p19(Ink4d) induction, suggesting that RNA-binding activity of PTB plays an
      important role in p19(Ink4d) induction. However, immunoprecipitation of
      ribonuclearprotein complexes plus quantitative real-time PCR analyses showed that
      PTB might not bind p19(Ink4d) mRNA, suggesting that PTB overexpression might
      trigger the other RNA-binding protein(s) to bind p19(Ink4d) mRNA. Subsequently,
      RNA electrophoretic mobility-shift assays revealed a 300-base segment (designated
      as B2) within the 3'UTR of p19(Ink4d) mRNA, with which the cytoplasmic lysates of
      PTB-overexpressing cells formed more prominent complexes than did control cell
      lysates. Insertion of B2 into a reporter construct increased the expression of
      the chimeric luciferase transcripts in transfected PTB-overexpressing cells but
      not in control cells; conversely, overexpression of B2-containing reporter
      construct in PTB-overexpressing cells abolished the induction of p19(Ink4d) mRNA.
      In sum, we have shown that PTB plays as a negative regulator in H1299 cell
      proliferation at least by inducing p19(Ink4d) expression at transcriptional and
      post-transcriptional levels.

PMID- 23536792
TI  - Transcriptome analysis of spermatogenically regressed, recrudescent and active
      phase testis of seasonally breeding wall lizards Hemidactylus flaviviridis.
AB  - BACKGROUND: Reptiles are phylogenically important group of organisms as mammals
      have evolved from them. Wall lizard testis exhibits clearly distinct morphology
      during various phases of a reproductive cycle making them an interesting model to
      study regulation of spermatogenesis. Studies on reptile spermatogenesis are
      negligible hence this study will prove to be an important resource.
      METHODOLOGY/PRINCIPAL FINDINGS: Histological analyses show complete regression of
      seminiferous tubules during regressed phase with retracted Sertoli cells and
      spermatognia. In the recrudescent phase, regressed testis regain cellular
      activity showing presence of normal Sertoli cells and developing germ cells. In
      the active phase, testis reaches up to its maximum size with enlarged
      seminiferous tubules and presence of sperm in seminiferous lumen. Total RNA
      extracted from whole testis of regressed, recrudescent and active phase of wall
      lizard was hybridized on Mouse Whole Genome 8*60 K format gene chip. Microarray
      data from regressed phase was deemed as control group. Microarray data were
      validated by assessing the expression of some selected genes using Quantitative
      Real-Time PCR. The genes prominently expressed in recrudescent and active phase
      testis are cytoskeleton organization GO 0005856, cell growth GO 0045927, GTpase
      regulator activity GO: 0030695, transcription GO: 0006352, apoptosis GO: 0006915
      and many other biological processes. The genes showing higher expression in
      regressed phase belonged to functional categories such as negative regulation of
      macromolecule metabolic process GO: 0010605, negative regulation of gene
      expression GO: 0010629 and maintenance of stem cell niche GO: 0045165.
      CONCLUSION/SIGNIFICANCE: This is the first exploratory study profiling
      transcriptome of three drastically different conditions of any reptilian testis.
      The genes expressed in the testis during regressed, recrudescent and active phase
      of reproductive cycle are in concordance with the testis morphology during these
      phases. This study will pave the way for deeper insight into regulation and
      evolution of gene regulatory mechanisms in spermatogenesis.

PMID- 23536793
TI  - Transcriptomic response of porcine PBMCs to vaccination with tetanus toxoid as a
      model antigen.
AB  - The aim of the present study was to characterize in vivo genome-wide
      transcriptional responses to immune stimulation in order to get insight into the
      resulting changes of allocation of resources. Vaccination with tetanus toxoid was
      used as a model for a mixed Th1 and Th2 immune response in pig. Expression
      profiles of PBMCs (peripheral blood mononuclear cells) before and at 12 time
      points over a period of four weeks after initial and booster vaccination at day
      14 were studied by use of Affymetrix GeneChip microarrays and Ingenuity Pathway
      Analysis (IPA). The transcriptome data in total comprised more than 5000 genes
      with different transcript abundances (DE-genes). Within the single time stages
      the numbers of DE-genes were between several hundred and more than 1000.
      Ingenuity Pathway Analysis mainly revealed canonical pathways of cellular immune
      response and cytokine signaling as well as a broad range of processes in cellular
      and organismal growth, proliferation and development, cell signaling,
      biosynthesis and metabolism. Significant changes in the expression profiles of
      PBMCs already occurred very early after immune stimulation. At two hours after
      the first vaccination 679 DE-genes corresponding to 110 canonical pathways of
      cytokine signaling, cellular immune response and other multiple cellular
      functions were found. Immune competence and global disease resistance are
      heritable but difficult to measure and to address by breeding. Besides QTL
      mapping of immune traits gene expression profiling facilitates the detection of
      functional gene networks and thus functional candidate genes.

PMID- 23536794
TI  - Catalytic nanoceria are preferentially retained in the rat retina and are not
      cytotoxic after intravitreal injection.
AB  - Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical
      scavenging activities. The ability of nanoceria to maintain cellular redox
      balance makes them ideal candidates for treatment of retinal diseases whose
      development is tightly associated with oxidative damage. We have demonstrated
      that our stable water-dispersed nanoceria delay photoreceptor cell degeneration
      in rodent models and prevent pathological retinal neovascularization in vldlr
      mutant mice. The objectives of the current study were to determine the temporal
      and spatial distributions of nanoceria after a single intravitreal injection, and
      to determine if nanoceria had any toxic effects in healthy rat retinas. Using
      inductively-coupled plasma mass spectrometry (ICP-MS), we discovered that
      nanoceria were rapidly taken up by the retina and were preferentially retained in
      this tissue even after 120 days. We also did not observe any acute or long-term
      negative effects of nanoceria on retinal function or cytoarchitecture even after
      this long-term exposure. Because nanoceria are effective at low dosages, nontoxic
      and are retained in the retina for extended periods, we conclude that nanoceria
      are promising ophthalmic therapeutics for treating retinal diseases known to
      involve oxidative stress in their pathogeneses.

PMID- 23536795
TI  - X-ray phase-contrast CT of a pancreatic ductal adenocarcinoma mouse model.
AB  - To explore the potential of grating-based x-ray phase-contrast computed
      tomography (CT) for preclinical research, a genetically engineered mouse model of
      pancreatic ductal adenocarcinoma (PDAC) was investigated. One ex-vivo mouse
      specimen was scanned with different grating-based phase-contrast CT imaging
      setups covering two different settings: i) high-resolution synchrotron radiation
      (SR) imaging and ii) dose-reduced imaging using either synchrotron radiation or a
      conventional x-ray tube source. These experimental settings were chosen to assess
      the potential of phase-contrast imaging for two different types of application:
      i) high-performance imaging for virtual microscopy applications and ii)
      biomedical imaging with increased soft-tissue contrast for in-vivo applications.
      For validation and as a reference, histological slicing and magnetic resonance
      imaging (MRI) were performed on the same mouse specimen. For each x-ray imaging
      setup, attenuation and phase-contrast images were compared visually with regard
      to contrast in general, and specifically concerning the recognizability of
      lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to
      noise ratios (CNR) of selected regions of interest (ROI) in the attenuation
      images and the phase images were analyzed and compared. It was found that both
      for virtual microscopy and for in-vivo applications, there is great potential for
      phase-contrast imaging: in the SR-based benchmarking data, fine details about
      tissue composition are accessible in the phase images and the visibility of solid
      tumor tissue under dose-reduced conditions is markedly superior in the phase
      images. The present study hence demonstrates improved diagnostic value with phase
      contrast CT in a mouse model of a complex endogenous cancer, promoting the use
      and further development of grating-based phase-contrast CT for biomedical imaging
      applications.

PMID- 23536796
TI  - Brain changes in long-term zen meditators using proton magnetic resonance
      spectroscopy and diffusion tensor imaging: a controlled study.
AB  - INTRODUCTION: This work aimed to determine whether (1)H magnetic resonance
      imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging
      (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation
      and psychological variables in long-term Zen meditators compared to healthy non
      meditator controls. MATERIALS AND METHODS: Design. Controlled, cross-sectional
      study. Sample. Meditators were recruited from a Zen Buddhist monastery. The
      control group was recruited from hospital staff. Meditators were administered
      questionnaires on anxiety, depression, cognitive impairment and mindfulness. (1)H
      MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami,
      both hippocampi, the posterior superior parietal lobule (PSPL) and posterior
      cingulate gyrus. Predefined areas of the brain were measured for diffusivity
      (ADC) and fractional anisotropy (FA) by MR-DTI. RESULTS: Myo-inositol (mI) was
      increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl
      aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left
      thalamus in meditators. We found a significant positive correlation between mI in
      the posterior cingulate and years of meditation (r = 0.518; p = .019). We also
      found significant negative correlations between Glu (r = -0.452; p = .045), NAA
      (r = -0.617; p = .003) and NAA/Cr (r = -0.448; P = .047) in the left thalamus and
      years of meditation. Meditators showed a lower Apparent Diffusion Coefficient
      (ADC) in the left posterior parietal white matter than did controls, and the ADC
      was negatively correlated with years of meditation (r = -0.4850, p = .0066).
      CONCLUSIONS: The results are consistent with the view that mI, Glu and NAA are
      the most important altered metabolites. This study provides evidence of subtle
      abnormalities in neuronal function in regions of the white matter in meditators.

PMID- 23536797
TI  - Rational design of a fibroblast growth factor 21-based clinical candidate,
      LY2405319.
AB  - Fibroblast growth factor 21 is a novel hormonal regulator with the potential to
      treat a broad variety of metabolic abnormalities, such as type 2 diabetes,
      obesity, hepatic steatosis, and cardiovascular disease. Human recombinant wild
      type FGF21 (FGF21) has been shown to ameliorate metabolic disorders in rodents
      and non-human primates. However, development of FGF21 as a drug is challenging
      and requires re-engineering of its amino acid sequence to improve protein
      expression and formulation stability. Here we report the design and
      characterization of a novel FGF21 variant, LY2405319. To enable the development
      of a potential drug product with a once-daily dosing profile, in a preserved,
      multi-use formulation, an additional disulfide bond was introduced in FGF21
      through Leu118Cys and Ala134Cys mutations. FGF21 was further optimized by
      deleting the four N-terminal amino acids, His-Pro-Ile-Pro (HPIP), which was
      subject to proteolytic cleavage. In addition, to eliminate an O-linked
      glycosylation site in yeast a Ser167Ala mutation was introduced, thus allowing
      large-scale, homogenous protein production in Pichia pastoris. Altogether re
      engineering of FGF21 led to significant improvements in its biopharmaceutical
      properties. The impact of these changes was assessed in a panel of in vitro and
      in vivo assays, which confirmed that biological properties of LY2405319 were
      essentially identical to FGF21. Specifically, subcutaneous administration of
      LY2405319 in ob/ob and diet-induced obese (DIO) mice over 7-14 days resulted in a
      25-50% lowering of plasma glucose coupled with a 10-30% reduction in body weight.
      Thus, LY2405319 exhibited all the biopharmaceutical and biological properties
      required for initiation of a clinical program designed to test the hypothesis
      that administration of exogenous FGF21 would result in effects on disease-related
      metabolic parameters in humans.

PMID- 23536798
TI  - In situ coral reef oxygen metabolism: an eddy correlation study.
AB  - Quantitative studies of coral reefs are challenged by the three-dimensional hard
      structure of reefs and the high spatial variability and temporal dynamics of
      their metabolism. We used the non-invasive eddy correlation technique to examine
      respiration and photosynthesis rates, through O2 fluxes, from reef crests and
      reef slopes in the Florida Keys, USA. We assessed how the photosynthesis and
      respiration of different reef habitats is controlled by light and hydrodynamics.
      Numerous fluxes (over a 0.25 h period) were as high as 4500 mmol O2 m(-2) d(-1),
      which can only be explained by efficient light utilization by the phototrophic
      community and the complex canopy structure of the reef, having a many-fold larger
      surface area than its horizontal projection. Over diel cycles, the reef crest was
      net autotrophic, whereas on the reef slope oxygen production and respiration were
      balanced. The autotrophic nature of the shallow reef crests implies that the
      export of organics is an important source of primary production for the larger
      area. Net oxygen production on the reef crest was proportional to the light
      intensity, up to 1750 umol photons m(-2) s(-1) and decreased thereafter as
      respiration was stimulated by high current velocities coincident with peak light
      levels. Nighttime respiration rates were also stimulated by the current velocity,
      through enhanced ventilation of the porous framework of the reef. Respiration
      rates were the highest directly after sunset, and then decreased during the night
      suggesting that highly labile photosynthates produced during the day fueled early
      night respiration. The reef framework was also important to the acquisition of
      nutrients as the ambient nitrogen stock in the water had sufficient capacity to
      support these high production rates across the entire reef width. These direct
      measurements of complex reefs systems yielded high metabolic rates and dynamics
      that can only be determined through in situ, high temporal resolution
      measurements.

PMID- 23536799
TI  - Amino acid substitutions in cold-adapted proteins from Halorubrum lacusprofundi,
      an extremely halophilic microbe from antarctica.
AB  - The halophilic Archaeon Halorubrum lacusprofundi, isolated from the perennially
      cold and hypersaline Deep Lake in Antarctica, was recently sequenced and compared
      to 12 Haloarchaea from temperate climates by comparative genomics. Amino acid
      substitutions for 604 H. lacusprofundi proteins belonging to conserved
      haloarchaeal orthologous groups (cHOGs) were determined and found to occur at
      7.85% of positions invariant in proteins from mesophilic Haloarchaea. The
      following substitutions were observed most frequently: (a) glutamic acid with
      aspartic acid or alanine; (b) small polar residues with other small polar or non
      polar amino acids; (c) small non-polar residues with other small non-polar
      residues; (d) aromatic residues, especially tryptophan, with other aromatic
      residues; and (e) some larger polar residues with other similar residues. Amino
      acid substitutions for a cold-active H. lacusprofundi beta-galactosidase were
      then examined in the context of a homology modeled structure at residues
      invariant in homologous enzymes from mesophilic Haloarchaea. Similar
      substitutions were observed as in the genome-wide approach, with the surface
      accessible regions of beta-galactosidase displaying reduced acidity and increased
      hydrophobicity, and internal regions displaying mainly subtle changes among
      smaller non-polar and polar residues. These findings are consistent with H.
      lacusprofundi proteins displaying amino acid substitutions that increase
      structural flexibility and protein function at low temperature. We discuss the
      likely mechanisms of protein adaptation to a cold, hypersaline environment on
      Earth, with possible relevance to life elsewhere.

PMID- 23536800
TI  - BRAHMA ATPase of the SWI/SNF chromatin remodeling complex acts as a positive
      regulator of gibberellin-mediated responses in arabidopsis.
AB  - SWI/SNF chromatin remodeling complexes perform a pivotal function in the
      regulation of eukaryotic gene expression. Arabidopsis (Arabidopsis thaliana)
      mutants in major SWI/SNF subunits display embryo-lethal or dwarf phenotypes,
      indicating their critical role in molecular pathways controlling development and
      growth. As gibberellins (GA) are major positive regulators of plant growth, we
      wanted to establish whether there is a link between SWI/SNF and GA signaling in
      Arabidopsis. This study revealed that in brm-1 plants, depleted in SWI/SNF BRAHMA
      (BRM) ATPase, a number of GA-related phenotypic traits are GA-sensitive and that
      the loss of BRM results in markedly decreased level of endogenous bioactive GA.
      Transcriptional profiling of brm-1 and the GA biosynthesis mutant ga1-3, as well
      as the ga1-3/brm-1 double mutant demonstrated that BRM affects the expression of
      a large set of GA-responsive genes including genes responsible for GA
      biosynthesis and signaling. Furthermore, we found that BRM acts as an activator
      and directly associates with promoters of GA3ox1, a GA biosynthetic gene, and
      SCL3, implicated in positive regulation of the GA pathway. Many GA-responsive
      gene expression alterations in the brm-1 mutant are likely due to depleted levels
      of active GAs. However, the analysis of genetic interactions between BRM and the
      DELLA GA pathway repressors, revealed that BRM also acts on GA-responsive genes
      independently of its effect on GA level. Given the central position occupied by
      SWI/SNF complexes within regulatory networks controlling fundamental biological
      processes, the identification of diverse functional intersections of BRM with GA
      dependent processes in this study suggests a role for SWI/SNF in facilitating
      crosstalk between GA-mediated regulation and other cellular pathways.

PMID- 23536802
TI  - Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene
      knock down.
AB  - Laser based transfection methods have proven to be an efficient and gentle
      alternative to established molecule delivery methods like lipofection or
      electroporation. Among the laser based methods, gold nanoparticle mediated laser
      transfection bears the major advantage of high throughput and easy usability.
      This approach uses plasmon resonances on gold nanoparticles unspecifically
      attached to the cell membrane to evoke transient and spatially defined cell
      membrane permeabilization. In this study, we explore the parameter regime for
      gold nanoparticle mediated laser transfection for the delivery of molecules into
      cell lines and prove its suitability for siRNA mediated gene knock down. The
      developed setup allows easy usage and safe laser operation in a normal lab
      environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at
      a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the
      sample of up to 200 mm/s were tested without a decline in perforation efficiency.
      This velocity leads to a process speed of ~8 s per well of a 96 well plate. The
      optimal particle density was determined to be ~6 particles per cell using
      environmental scanning electron microscopy. Applying the optimized parameters
      transfection efficiencies of 88% were achieved in canine pleomorphic adenoma
      ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell
      viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by
      fluorescence repression and western blot analysis. On basis of our findings and
      established mathematical models we suppose a mixed transfection mechanism
      consisting of thermal and multiphoton near field effects. Our findings emphasize
      that gold nanoparticle mediated laser transfection provides an excellent tool for
      molecular delivery for both, high throughput purposes and the transfection of
      sensitive cells types.

PMID- 23536801
TI  - Neocortex and allocortex respond differentially to cellular stress in vitro and
      aging in vivo.
AB  - In Parkinson's and Alzheimer's diseases, the allocortex accumulates aggregated
      proteins such as synuclein and tau well before neocortex. We present a new high
      throughput model of this topographic difference by microdissecting neocortex and
      allocortex from the postnatal rat and treating them in parallel fashion with
      toxins. Allocortical cultures were more vulnerable to low concentrations of the
      proteasome inhibitors MG132 and PSI but not the oxidative poison H2O2. The
      proteasome appeared to be more impaired in allocortex because MG132 raised
      ubiquitin-conjugated proteins and lowered proteasome activity in allocortex more
      than neocortex. Allocortex cultures were more vulnerable to MG132 despite greater
      MG132-induced rises in heat shock protein 70, heme oxygenase 1, and catalase.
      Proteasome subunits PA700 and PA28 were also higher in allocortex cultures,
      suggesting compensatory adaptations to greater proteasome impairment. Glutathione
      and ceruloplasmin were not robustly MG132-responsive and were basally higher in
      neocortical cultures. Notably, neocortex cultures became as vulnerable to MG132
      as allocortex when glutathione synthesis or autophagic defenses were inhibited.
      Conversely, the glutathione precursor N-acetyl cysteine rendered allocortex
      resilient to MG132. Glutathione and ceruloplasmin levels were then examined in
      vivo as a function of age because aging is a natural model of proteasome
      inhibition and oxidative stress. Allocortical glutathione levels rose linearly
      with age but were similar to neocortex in whole tissue lysates. In contrast,
      ceruloplasmin levels were strikingly higher in neocortex at all ages and rose
      linearly until middle age. PA28 levels rose with age and were higher in
      allocortex in vivo, also paralleling in vitro data. These neo- and allocortical
      differences have implications for the many studies that treat the telencephalic
      mantle as a single unit. Our observations suggest that the topographic
      progression of protein aggregations through the cerebrum may reflect differential
      responses to low level protein-misfolding stress but also reveal impressive
      compensatory adaptations in allocortex.

PMID- 23536804
TI  - Overestimation of vitamin a supplementation coverage from district tally sheets
      demonstrates importance of population-based surveys for program improvement:
      lessons from Tanzania.
AB  - BACKGROUND: Tanzania has conducted a national twice-yearly Vitamin A
      supplementation (VAS) campaign since 2001. Administrative coverage rates based on
      tally sheets consistently report >90% coverage; however the accuracy of these
      rates are uncertain due to potential errors in tally sheets and their
      aggregation, incomplete or inaccurate reporting from distribution sites, and
      underestimating the target population. OBJECTIVES: The post event coverage survey
      in Mainland Tanzania sought to validate tally-sheet based national coverage
      estimates of VAS and deworming for the June 2010 mass distribution round, and to
      characterize children missed by the national campaign. METHODS: WHO/EPI
      randomized cross-sectional cluster sampling methodology was adapted for this
      study, using 30 clusters by 40 individuals (n = 1200), in addition to key
      informant interviews. Households with children 6-59 months of age were included
      in the study (12-59 months for deworming analysis). Chi-squared tests and
      logistic regression analysis were used to test differences between children
      reached and not reached by VAS. Data was collected within six weeks of the June
      2010 round. RESULTS: A total of 1203 children, 58 health workers, 30 village
      leaders and 45 community health workers were sampled. Preschool VAS coverage was
      65% (95% CI: 62.7-68.1), approximately 30% lower than tally-sheet coverage
      estimates. Factors associated with not receiving VAS were urban residence [OR =
      3.31; p = 0.01], caretakers who did not hear about the campaign [OR = 48.7;
      p<0.001], and Muslim households [OR<3.25; p<0.01]. There were no significant
      differences in VAS coverage by child sex or age, or maternal age or education.
      CONCLUSION: Coverage estimation for vitamin A supplementation programs is one of
      most powerful indicators of program success. National VAS coverage based on a
      tally-sheet system overestimated VAS coverage by ~30%. There is a need for
      representative population-based coverage surveys to complement and validate tally
      sheet estimates.

PMID- 23536803
TI  - Integration of multiple signaling regulates through apoptosis the differential
      osteogenic potential of neural crest-derived and mesoderm-derived Osteoblasts.
AB  - Neural crest-derived (FOb) and mesoderm-derived (POb) calvarial osteoblasts are
      characterized by distinct differences in their osteogenic potential. We have
      previously demonstrated that enhanced activation of endogenous FGF and Wnt
      signaling confers greater osteogenic potential to FOb. Apoptosis, a key player in
      bone formation, is the main focus of this study. In the current work, we have
      investigated the apoptotic activity of FOb and POb cells during differentiation.
      We found that lower apoptosis, as measured by caspase-3 activity is a major
      feature of neural crest-derived osteoblast which also have higher osteogenic
      capacity. Further investigation indicated TGF-beta signaling as main positive
      regulator of apoptosis in these two populations of calvarial osteoblasts, while
      BMP and canonical Wnt signaling negatively regulate the process. By either
      inducing or inhibiting these signaling pathways we could modulate apoptotic
      events and improve the osteogenic potential of POb. Taken together, our findings
      demonstrate that integration of multiple signaling pathways contribute to
      imparting greater osteogenic potential to FOb by decreasing apoptosis.

PMID- 23536805
TI  - Non-specific protein modifications by a phytochemical induce heat shock response
      for self-defense.
AB  - Accumulated evidence shows that some phytochemicals provide beneficial effects
      for human health. Recently, a number of mechanistic studies have revealed that
      direct interactions between phytochemicals and functional proteins play
      significant roles in exhibiting their bioactivities. However, their binding
      selectivities to biological molecules are considered to be lower due to their
      small and simple structures. In this study, we found that zerumbone, a bioactive
      sesquiterpene, binds to numerous proteins with little selectivity. Similar to
      heat-denatured proteins, zerumbone-modified proteins were recognized by heat
      shock protein 90, a constitutive molecular chaperone, leading to heat shock
      factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma
      cells. Furthermore, oral administration of this phytochemical up-regulated heat
      shock protein expressions in the livers of Sprague-Dawley rats. Interestingly,
      pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7
      cells as well as to the nematode Caenorhabditis elegans. It is also important to
      note that several phytochemicals with higher hydrophobicity or electrophilicity,
      including phenethyl isothiocyanate and curcumin, markedly induced heat shock
      proteins, whereas most of the tested nutrients did not. These results suggest
      that non-specific protein modifications by xenobiotic phytochemicals cause mild
      proteostress, thereby inducing heat shock response and leading to potentiation of
      protein quality control systems. We considered these bioactivities to be
      xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat
      shock response by phytochemicals may be a fundamental mechanism underlying their
      various bioactivities.

PMID- 23536806
TI  - Proteomic biomarkers for ageing the mosquito Aedes aegypti to determine risk of
      pathogen transmission.
AB  - Biomarkers of the age of mosquitoes are required to determine the risk of
      transmission of various pathogens as each pathogen undergoes a period of
      extrinsic incubation in the mosquito host. Using the 2-D Difference Gel
      Electrophoresis (2-D DIGE) procedure, we investigated the abundance of up to 898
      proteins from the Yellow Fever and dengue virus vector, Aedes aegypti, during
      ageing. By applying a mixed-effects model of protein expression, we identified
      five common patterns of abundance change during ageing and demonstrated an age
      related decrease in variance for four of these. This supported a search for
      specific proteins with abundance changes that remain tightly associated with
      ageing for use as ageing biomarkers. Using MALDI-TOF/TOF mass spectrometry we
      identified ten candidate proteins that satisfied strict biomarker discovery
      criteria (identified in two out of three multivariate analysis procedures and in
      two cohorts of mosquitoes). We validated the abundances of the four most suitable
      candidates (Actin depolymerising factor; ADF, Eukaryotic initiation factor 5A;
      eIF5A, insect cuticle protein Q17LN8, and Anterior fat body protein; AFP) using
      semi-quantitative Western analysis of individual mosquitoes of six ages. The
      redox-response protein Manganese superoxide dismutase (SOD2) and electron
      shuttling protein Electron transfer oxidoreductase (ETO) were subject to post
      translational modifications affecting their charge states with potential effects
      on function. For the four candidates we show remarkably consistent decreases in
      abundance during ageing, validating initial selections. In particular, the
      abundance of AFP is an ideal biomarker candidate for whether a female mosquito
      has lived long enough to be capable of dengue virus transmission. We have
      demonstrated proteins to be a suitable class of ageing biomarkers in mosquitoes
      and have identified candidates for epidemiological studies of dengue and the
      evaluation of new disease reduction projects targeting mosquito longevity.

PMID- 23536808
TI  - The symbiosis between Lophelia pertusa and Eunice norvegica stimulates coral
      calcification and worm assimilation.
AB  - We investigated the interactions between the cold-water coral Lophelia pertusa
      and its associated polychaete Eunice norvegica by quantifying carbon (C) and
      nitrogen (N) budgets of tissue assimilation, food partitioning, calcification and
      respiration using (13)C and (15)N enriched algae and zooplankton as food sources.
      During incubations both species were kept either together or in separate chambers
      to study the net outcome of their interaction on the above mentioned processes.
      The stable isotope approach also allowed us to follow metabolically derived
      tracer C further into the coral skeleton and therefore estimate the effect of the
      interaction on coral calcification. Results showed that food assimilation by the
      coral was not significantly elevated in presence of E. norvegica but food
      assimilation by the polychaete was up to 2 to 4 times higher in the presence of
      the coral. The corals kept assimilation constant by increasing the consumption of
      smaller algae particles less favored by the polychaete while the assimilation of
      Artemia was unaffected by the interaction. Total respiration of tracer C did not
      differ among incubations, although E. norvegica enhanced coral calcification up
      to 4 times. These results together with the reported high abundance of E.
      norvegica in cold-water coral reefs, indicate that the interactions between L.
      pertusa and E. norvegica can be of high importance for ecosystem functioning.

PMID- 23536807
TI  - A genome-wide association study for primary open angle glaucoma and macular
      degeneration reveals novel Loci.
AB  - Glaucoma and age-related macular degeneration (AMD) are the two leading causes of
      visual loss in the United States. We utilized a novel study design to perform a
      genome-wide association for both primary open angle glaucoma (POAG) and AMD. This
      study design utilized a two-stage process for hypothesis generation and
      validation, in which each disease cohort was utilized as a control for the other.
      A total of 400 POAG patients and 400 AMD patients were ascertained and genotyped
      at 500,000 loci. This study identified a novel association of complement
      component 7 (C7) to POAG. Additionally, an association of central corneal
      thickness, a known risk factor for POAG, was found to be associated with
      ribophorin II (RPN2). Linked monogenic loci for POAG and AMD were also evaluated
      for evidence of association, none of which were found to be significantly
      associated. However, several yielded putative associations requiring validation.
      Our data suggest that POAG is more genetically complex than AMD, with no common
      risk alleles of large effect.

PMID- 23536809
TI  - United states acculturation and cancer patients' end-of-life care.
AB  - BACKGROUND: Culture shapes how people understand illness and death, but few
      studies examine whether acculturation influences patients' end-of-life treatment
      preferences and medical care. METHODS AND FINDINGS: In this multi-site,
      prospective, longitudinal cohort study of terminally-ill cancer patients and
      their caregivers (n = 171 dyads), trained interviewers administered the United
      States Acculturation Scale (USAS). The USAS is a 19-item scale developed to
      assess the degree of "Americanization" in first generation or non-US born
      caregivers of terminally-ill cancer patients. We evaluated the internal
      consistency, concurrent, criterion, and content validity of the USAS. We also
      examined whether caregivers' USAS scores predicted patients' communication,
      treatment preferences, and end-of-life medical care in multivariable models that
      corrected for significant confounding influences (e.g. education, country of
      origin, English proficiency). The USAS measure was internally consistent
      (Cronbach alpha = 0.98); and significantly associated with US birthplace (r =
      0.66, P<0.0001). USAS scores were predictive of patients' preferences for
      prognostic information (AOR = 1.31, 95% CI:1.00-1.72), but not comfort asking
      physicians' questions about care (AOR 1.23, 95% CI:0.87-1.73). They predicted
      patients' preferences for feeding tubes (AOR = 0.68, 95% CI:0.49-0.99) and wish
      to avoid dying in an intensive care unit (AOR = 1.36, 95% CI:1.05-1.76). Scores
      indicating greater acculturation were also associated with increased odds of
      patient participation in clinical trials (AOR = 2.20, 95% CI:1.28-3.78), compared
      with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR
      = 1.59, 95% CI:1.20-2.12). CONCLUSION: The USAS is a reliable and valid measure
      of "Americanization" associated with advanced cancer patients' end-of-life
      preferences and care. USAS scores indicating greater caregiver acculturation were
      associated with increased odds of patient participation in cancer treatment
      (chemotherapy, clinical trials) compared with lower scores. Future studies should
      examine the effects of acculturation on end-of-life care to identify patient and
      provider factors that explain these effects and targets for future interventions
      to improve care (e.g., by designing more culturally-competent health education
      materials).

PMID- 23536810
TI  - Management of deep brain stimulator battery failure: battery estimators, charge
      density, and importance of clinical symptoms.
AB  - OBJECTIVE: We aimed in this investigation to study deep brain stimulation (DBS)
      battery drain with special attention directed toward patient symptoms prior to
      and following battery replacement. BACKGROUND: Previously our group developed web
      based calculators and smart phone applications to estimate DBS battery life
      (http://mdc.mbi.ufl.edu/surgery/dbs-battery-estimator). METHODS: A cohort of 320
      patients undergoing DBS battery replacement from 2002-2012 were included in an
      IRB approved study. Statistical analysis was performed using SPSS 20.0 (IBM,
      Armonk, NY). RESULTS: The mean charge density for treatment of Parkinson's
      disease was 7.2 uC/cm(2)/phase (SD = 3.82), for dystonia was 17.5 uC/cm(2)/phase
      (SD = 8.53), for essential tremor was 8.3 uC/cm(2)/phase (SD = 4.85), and for OCD
      was 18.0 uC/cm(2)/phase (SD = 4.35). There was a significant relationship between
      charge density and battery life (r = -.59, p<.001), as well as total power and
      battery life (r = -.64, p<.001). The UF estimator (r = .67, p<.001) and the
      Medtronic helpline (r = .74, p<.001) predictions of battery life were
      significantly positively associated with actual battery life. Battery status
      indicators on Soletra and Kinetra were poor predictors of battery life. In 38
      cases, the symptoms improved following a battery change, suggesting that the
      neurostimulator was likely responsible for symptom worsening. For these cases,
      both the UF estimator and the Medtronic helpline were significantly correlated
      with battery life (r = .65 and r = .70, respectively, both p<.001). CONCLUSIONS:
      Battery estimations, charge density, total power and clinical symptoms were
      important factors. The observation of clinical worsening that was rescued
      following neurostimulator replacement reinforces the notion that changes in
      clinical symptoms can be associated with battery drain.

PMID- 23536811
TI  - Characterization of functional TRPV1 channels in the sarcoplasmic reticulum of
      mouse skeletal muscle.
AB  - TRPV1 represents a non-selective cation channel activated by capsaicin, acidosis
      and high temperature. In the central nervous system where TRPV1 is highly
      expressed, its physiological role in nociception is clearly identified. In
      skeletal muscle, TRPV1 appears implicated in energy metabolism and exercise
      endurance. However, how as a Ca(2+) channel, it contributes to intracellular
      calcium concentration ([Ca(2+)]i) maintenance and muscle contraction remains
      unknown. Here, as in rats, we report that TRPV1 is functionally expressed in
      mouse skeletal muscle. In contrast to earlier reports, our analysis show TRPV1
      presence only at the sarcoplasmic reticulum (SR) membrane (preferably at the
      longitudinal part) in the proximity of SERCA1 pumps. Using intracellular Ca(2+)
      imaging, we directly accessed to the channel functionality in intact FDB mouse
      fibers. Capsaicin and resiniferatoxin, both agonists as well as high temperature
      (45 degrees C) elicited an increase in [Ca(2+)]i. TRPV1-inhibition by capsazepine
      resulted in a strong inhibition of TRPV1-mediated functional responses and
      abolished channel activation. Blocking the SR release (with ryanodine or
      dantrolene) led to a reduced capsaicin-induced Ca(2+) elevation suggesting that
      TRPV1 may participate to a secondary SR Ca(2+) liberation of greater amplitude.
      In conclusion, our experiments point out that TRPV1 is a functional SR Ca(2+)
      leak channel and may crosstalk with RyR1 in adult mouse muscle fibers.

PMID- 23536813
TI  - Mechanisms of population structuring in giant australian Cuttlefish Sepia apama.
AB  - While a suite of approaches have been developed to describe the scale, rate and
      spatial structure of exchange among populations, a lack of mechanistic
      understanding will invariably compromise predictions of population-level
      responses to ecosystem modification. In this study, we measured the energetics
      and sustained swimming capacity of giant Australian cuttlefish Sepia apama and
      combined these data with information on the life-history strategy, behaviour and
      circulation patterns experienced by the species to predict scales of connectivity
      throughout parts of their range. The swimming capacity of adult and juvenile S.
      apama was poor compared to most other cephalopods, with most individuals
      incapable of maintaining swimming above 15 cm s(-1). Our estimate of optimal
      swimming speed (6-7 cm s(-1)) and dispersal potential were consistent with the
      observed fine-scale population structure of the species. By comparing observed
      and predicted population connectivity, we identified several mechanisms that are
      likely to have driven fine-scale population structure in this species, which will
      assist in the interpretation of future population declines.

PMID- 23536812
TI  - Identification and analysis of the acetylated status of poplar proteins reveals
      analogous N-terminal protein processing mechanisms with other eukaryotes.
AB  - BACKGROUND: The N-terminal protein processing mechanism (NPM) including N
      terminal Met excision (NME) and N-terminal acetylation (N(alpha)-acetylation)
      represents a common protein co-translational process of some eukaryotes. However,
      this NPM occurred in woody plants yet remains unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: To reveal the NPM in poplar, we investigated the N(alpha)-acetylation
      status of poplar proteins during dormancy by combining tandem mass spectrometry
      with TiO2 enrichment of acetylated peptides. We identified 58 N-terminally
      acetylated (N(alpha)-acetylated) proteins. Most proteins (47, >81%) are subjected
      to N(alpha)-acetylation following the N-terminal removal of Met, indicating that
      N(alpha)-acetylation and NME represent a common NPM of poplar proteins.
      Furthermore, we confirm that poplar shares the analogous NME and N(alpha)
      acetylation (NPM) to other eukaryotes according to analysis of N-terminal
      features of these acetylated proteins combined with genome-wide identification of
      the involving methionine aminopeptidases (MAPs) and N-terminal acetyltransferase
      (Nat) enzymes in poplar. The N(alpha)-acetylated reactions and the involving
      enzymes of these poplar proteins are also identified based on those of yeast and
      human, as well as the subcellular location information of these poplar proteins.
      CONCLUSIONS/SIGNIFICANCE: This study represents the first extensive investigation
      of N(alpha)-acetylation events in woody plants, the results of which will provide
      useful resources for future unraveling the regulatory mechanisms of N(alpha)
      acetylation of proteins in poplar.

PMID- 23536814
TI  - Independent validation of an existing model enables prediction of hearing loss
      after childhood bacterial meningitis.
AB  - OBJECTIVE: This study aimed external validation of a formerly developed
      prediction model identifying children at risk for hearing loss after bacterial
      meningitis (BM). Independent risk factors included in the model are: duration of
      symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose
      level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether
      the model has potential in clinical practice. STUDY DESIGN: 116 Dutch school-age
      BM survivors were included in the validation cohort and screened for
      sensorineural hearing loss (>25 dB). Risk factors were obtained from medical
      records. The model was applied to the validation cohort and its performance was
      compared with the development cohort. Validation was performed by application of
      the model on the validation cohort and by assessment of discrimination and
      goodness of fit. Calibration was evaluated by testing deviations in intercept and
      slope. Multiple imputation techniques were used to deal with missing values.
      RESULTS: Risk factors were distributed equally between both cohorts.
      Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the
      development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness
      of fit was not significant in the validation cohort, implying good fit concerning
      the similarity of expected and observed cases. There were no significant
      differences in calibration slope and intercept. Sensitivity and negative
      predicted value were high, while specificity and positive predicted value were
      low which is comparable with findings in the development cohort. CONCLUSIONS:
      Performance of the model remained good in the validation cohort. This prediction
      model might be used as a screening tool and can help to identify those children
      that need special attention and a long follow-up period or more frequent auditory
      testing.

PMID- 23536815
TI  - The value of wetlands in protecting southeast louisiana from hurricane storm
      surges.
AB  - The Indian Ocean tsunami in 2004 and Hurricanes Katrina and Rita in 2005 have
      spurred global interest in the role of coastal wetlands and vegetation in
      reducing storm surge and flood damages. Evidence that coastal wetlands reduce
      storm surge and attenuate waves is often cited in support of restoring Gulf Coast
      wetlands to protect coastal communities and property from hurricane damage. Yet
      interdisciplinary studies combining hydrodynamic and economic analysis to explore
      this relationship for temperate marshes in the Gulf are lacking. By combining
      hydrodynamic analysis of simulated hurricane storm surges and economic valuation
      of expected property damages, we show that the presence of coastal marshes and
      their vegetation has a demonstrable effect on reducing storm surge levels, thus
      generating significant values in terms of protecting property in southeast
      Louisiana. Simulations for four storms along a sea to land transect show that
      surge levels decline with wetland continuity and vegetation roughness.
      Regressions confirm that wetland continuity and vegetation along the transect are
      effective in reducing storm surge levels. A 0.1 increase in wetland continuity
      per meter reduces property damages for the average affected area analyzed in
      southeast Louisiana, which includes New Orleans, by $99-$133, and a 0.001
      increase in vegetation roughness decreases damages by $24-$43. These reduced
      damages are equivalent to saving 3 to 5 and 1 to 2 properties per storm for the
      average area, respectively.

PMID- 23536816
TI  - Anisotropic alteration of scleral birefringence to uniaxial mechanical strain.
AB  - PURPOSE: To investigate the relationship between scleral mechanical properties,
      its birefringence, and the anisotropy of birefringence alteration in respect of
      the direction of the strain by using PS-OCT. METHODS: The scleral birefringence
      of thirty-nine porcine eyes was measured with a prototype PS-OCT. A rectangle
      strip of sclera with a width of 4 mm was dissected at the temporal region 5 mm
      apart from the optic nerve head. The strain and force were measured with a
      uniaxial tension tester as the sample was stretched with a speed of 1.8 mm/min
      after preconditioning. The birefringence of the sample was measured by PS-OCT at
      the center of the sample before applying, denoted as inherent birefringence, and
      after applying stretching of 6.5% strain. The birefringence alteration was
      obtained by these two measurements and correlations between birefringence and
      elastic parameters, tangent modulus, and structural stiffness were examined.
      Twenty and 19 porcine eyes were stretched in meridional or equatorial directions,
      respectively. RESULTS: A moderate positive correlation was found between the
      inherent birefringence and the structural stiffness. A moderate positive
      correlation was also found between the inherent birefringence and the tangent
      modulus. The birefringence increased by strains. Marginal significance was found
      in the birefringence alteration between meridional and equatorial strains, where
      the mean birefringence elevation by meridional strain was higher than that by
      equatorial strain. CONCLUSIONS: The birefringence was found to be altered by
      applying strain and also be related with inherent birefringence. This implies the
      birefringence of the sclera of the in vivo eye also could be affected by its
      mechanical property.

PMID- 23536817
TI  - Macrophage migration inhibitory factor inhibition is deleterious for high-fat
      diet-induced cardiac dysfunction.
AB  - AIMS: Development of metabolic syndrome is associated with impaired cardiac
      performance, mitochondrial dysfunction and pro-inflammatory cytokine increase,
      such as the macrophage migration inhibitory factor MIF. Depending on conditions,
      MIF may exert both beneficial and deleterious effects on the myocardium.
      Therefore, we tested whether pharmacological inhibition of MIF prevented or
      worsened metabolic syndrome-induced myocardial dysfunction. METHODS AND RESULTS:
      C57BL/6J mice were fed for ten weeks with 60% fat-enriched diet (HFD) or normal
      diet (ND). MIF inhibition was obtained by injecting mice twice a week with ISO-1,
      for three consecutive weeks. Then, triglycerides, cholesterol, fat mass, glucose
      intolerance, insulin resistance, ex vivo cardiac contractility, animal energetic
      substrate utilization assessed by indirect calorimetry and mitochondrial
      respiration and biogenesis were evaluated. HFD led to fat mass increase,
      dyslipidemia, glucose intolerance and insulin resistance. ISO-1 did not alter
      these parameters. However, MIF inhibition was responsible for HFD-induced cardiac
      dysfunction worsening. Mouse capacity to increase oxygen consumption in response
      to exercise was reduced in HFD compared to ND, and further diminished in ISO-1
      treated HFD group. Mitochondrial respiration was reduced in HFD mice, treated or
      not with ISO-1. Compared to ND, mitochondrial biogenesis signaling was
      upregulated in the HFD as demonstrated by mitochondrial DNA amount and PGC-1alpha
      expression. However, this increase in biogenesis was blocked by ISO-1 treatment.
      CONCLUSION: MIF inhibition achieved by ISO-1 was responsible for a reduction in
      HFD-induced mitochondrial biogenesis signaling that could explain majored cardiac
      dysfunction observed in HFD mice treated with MIF inhibitor.

PMID- 23536818
TI  - Single-Cell DNA barcoding using sequences from the small subunit rRNA and
      internal transcribed spacer region identifies new species of Trichonympha and
      Trichomitopsis from the hindgut of the termite Zootermopsis angusticollis.
AB  - To aid in their digestion of wood, lower termites are known to harbour a diverse
      community of prokaryotes as well as parabasalid and oxymonad protist symbionts.
      One of the best-studied lower termite gut communities is that of Zootermopsis
      angusticollis which has been known for almost 100 years to possess 3 species of
      Trichonympha (T. campanula, T. collaris, and T. sphaerica), 1 species of
      Trichomitopsis (T. termopsidis), as well as smaller flagellates. We have re
      assessed this community by sequencing the small subunit (SSU) rRNA gene and the
      internal transcribed spacer (ITS) region from a large number of single
      Trichonympha and Trichomitopsis cells for which morphology was also documented.
      Based on phylogenetic clustering and sequence divergence, we identify 3 new
      species: Trichonympha postcylindrica, Trichomitopsis minor, and Trichomitopsis
      parvus spp. nov. Once identified by sequencing, the morphology of the isolated
      cells for all 3 new species was re-examined and found to be distinct from the
      previously described species: Trichonympha postcylindrica can be morphologically
      distinguished from the other Trichonympha species by an extension on its
      posterior end, whereas Trichomitopsis minor and T. parvus are smaller than T.
      termopsidis but similar in size to each other and cannot be distinguished based
      on morphology using light microscopy. Given that Z. angusticollis has one of the
      best characterized hindgut communities, the near doubling of the number of the
      largest and most easily identifiable symbiont species suggests that the diversity
      of hindgut symbionts is substantially underestimated in other termites as well.
      Accurate descriptions of the diversity of these microbial communities are
      essential for understanding hindgut ecology and disentangling the interactions
      among the symbionts, and molecular barcoding should be a priority for these
      systems.

PMID- 23536819
TI  - The C. elegans Homolog of RBBP6 (RBPL-1) regulates fertility through controlling
      cell proliferation in the germline and nutrient synthesis in the intestine.
AB  - RBBP6 (retinoblastoma binding protein 6, also known as PACT or P2P-R in humans)
      is a multi-domain protein that functions in multiple processes, such as mitosis,
      cell differentiation, and cell apoptosis. RBBP6 is evolutionarily conserved and
      is present in unicellular organisms to mammals. Studies of RBBP6 have mostly
      focused on its RB- and p53-binding domains, which are found exclusively in
      mammals. Here, we investigated the C. elegans homolog of RBBP6 to explore the
      functional roles of its other domains. We found that RBPL-1, the homolog of RBBP6
      in C. elegans, is indispensable for worm development. RNAi silencing of rbpl-1
      led to embryonic lethality, as well as defects in oocyte production and intestine
      development. rbpl-1 RNAi worms showed defects in germ cell proliferation,
      suggesting that RBPL-1 regulates mitosis. Moreover, RNAi silencing of rbpl-1
      inhibited nutrient synthesis in the worm intestine. RBPL-1, as a nucleolus
      protein, was found to be expressed in diverse tissues and necessary for both
      germline and soma development. Using microarray analysis, we identified ~700
      genes whose expression levels were changed at least 10-fold in rbpl-1 worms. We
      propose that RBPL-1, like its yeast homolog, may regulate gene expression as an
      mRNA cleavage and polyadenylation factor. Taken together, the findings from this
      study reveal that RBPL-1 plays a pivotal role in C. elegans germline and soma
      development, suggesting that the functions of RBBP6 are conserved in diverse
      eukaryotic species.

PMID- 23536820
TI  - Comparative GO: a web application for comparative gene ontology and gene ontology
      based gene selection in bacteria.
AB  - The primary means of classifying new functions for genes and proteins relies on
      Gene Ontology (GO), which defines genes/proteins using a controlled vocabulary in
      terms of their Molecular Function, Biological Process and Cellular Component. The
      challenge is to present this information to researchers to compare and discover
      patterns in multiple datasets using visually comprehensible and user-friendly
      statistical reports. Importantly, while there are many GO resources available for
      eukaryotes, there are none suitable for simultaneous, graphical and statistical
      comparison between multiple datasets. In addition, none of them supports
      comprehensive resources for bacteria. By using Streptococcus pneumoniae as a
      model, we identified and collected GO resources including genes, proteins,
      taxonomy and GO relationships from NCBI, UniProt and GO organisations. Then, we
      designed database tables in PostgreSQL database server and developed a Java
      application to extract data from source files and loaded into database
      automatically. We developed a PHP web application based on Model-View-Control
      architecture, used a specific data structure as well as current and novel
      algorithms to estimate GO graphs parameters. We designed different navigation and
      visualization methods on the graphs and integrated these into graphical reports.
      This tool is particularly significant when comparing GO groups between multiple
      samples (including those of pathogenic bacteria) from different sources
      simultaneously. Comparing GO protein distribution among up- or down-regulated
      genes from different samples can improve understanding of biological pathways,
      and mechanism(s) of infection. It can also aid in the discovery of genes
      associated with specific function(s) for investigation as a novel vaccine or
      therapeutic targets. AVAILABILITY: http://turing.ersa.edu.au/BacteriaGO.

PMID- 23536821
TI  - Protein interactions in genome maintenance as novel antibacterial targets.
AB  - Antibacterial compounds typically act by directly inhibiting essential bacterial
      enzyme activities. Although this general mechanism of action has fueled
      traditional antibiotic discovery efforts for decades, new antibiotic development
      has not kept pace with the emergence of drug resistant bacterial strains. These
      limitations have severely restricted the therapeutic tools available for treating
      bacterial infections. Here we test an alternative antibacterial lead-compound
      identification strategy in which essential protein-protein interactions are
      targeted rather than enzymatic activities. Bacterial single-stranded DNA-binding
      proteins (SSBs) form conserved protein interaction "hubs" that are essential for
      recruiting many DNA replication, recombination, and repair proteins to SSB/DNA
      nucleoprotein substrates. Three small molecules that block SSB/protein
      interactions are shown to have antibacterial activity against diverse bacterial
      species. Consistent with a model in which the compounds target multiple
      SSB/protein interactions, treatment of Bacillus subtilis cultures with the
      compounds leads to rapid inhibition of DNA replication and recombination, and
      ultimately to cell death. The compounds also have unanticipated effects on
      protein synthesis that could be due to a previously unknown role for SSB/protein
      interactions in translation or to off-target effects. Our results highlight the
      potential of targeting protein-protein interactions, particularly those that
      mediate genome maintenance, as a powerful approach for identifying new
      antibacterial compounds.

PMID- 23536822
TI  - Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.
AB  - BACKGROUND: Age at natural menopause (ANM) is a complex trait with high
      heritability and is associated with several major hormonal-related diseases.
      Recently, several genome-wide association studies (GWAS), conducted exclusively
      among women of European ancestry, have discovered dozens of genetic loci
      influencing ANM. No study has been conducted to evaluate whether these findings
      can be generalized to Chinese women. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated
      the index single nucleotide polymorphisms (SNPs) in 19 GWAS-identified genetic
      susceptibility loci for ANM among 3,533 Chinese women who had natural menopause.
      We also investigated 3 additional SNPs which were in LD with the index SNP in
      European-ancestry but not in Asian-ancestry populations. Two genetic risk scores
      (GRS) were calculated to summarize SNPs across multiple loci one for all SNPs
      tested (GRSall), and one for SNPs which showed association in our study (GRSsel).
      All 22 SNPs showed the same association direction as previously reported. Eight
      SNPs were nominally statistically significant with P<=0.05: rs4246511 (RHBDL2),
      rs12461110 (NLRP11), rs2307449 (POLG), rs12611091 (BRSK1), rs1172822 (BRSK1),
      rs365132 (UIMC1), rs2720044 (ASH2L), and rs7246479 (TMEM150B). Especially, SNPs
      rs4246511, rs365132, rs1172822, and rs7246479 remained significant even after
      Bonferroni correction. Significant associations were observed for GRS. Women in
      the highest quartile began menopause 0.7 years (P = 3.24*10(-9)) and 0.9 years (P
      = 4.61*10(-11)) later than those in the lowest quartile for GRSsel and GRSall,
      respectively. CONCLUSIONS: Among the 22 investigated SNPs, eight showed
      associations with ANM (P<0.05) in our Chinese population. Results from this study
      extend some recent GWAS findings to the Asian-ancestry population and may guide
      future efforts to identify genetic determination of menopause.

PMID- 23536823
TI  - Expression and regulation of nampt in human islets.
AB  - Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the
      mammalian NAD+ biosynthesis of a salvage pathway and exists in 2 known forms,
      intracellular Nampt (iNampt) and a secreted form, extracellular Nampt (eNampt).
      eNampt can generate an intermediate product, nicotinamide mononucleotide (NMN),
      which has been reported to support insulin secretion in pancreatic islets. Nampt
      has been reported to be expressed in the pancreas but islet specific expression
      has not been adequately defined. The aim of this study was to characterize Nampt
      expression, secretion and regulation by glucose in human islets. Gene and protein
      expression of Nampt was assessed in human pancreatic tissue and isolated islets
      by qRT-PCR and immunofluorescence/confocal imaging respectively. Variable amounts
      of Nampt mRNA were detected in pancreatic tissue and isolated islets.
      Immunofluorescence staining for Nampt was found in the exocrine and endocrine
      tissue of fetal pancreas. However, in adulthood, Nampt expression was localized
      predominantly in beta cells. Isolated human islets secreted increasing amounts of
      eNampt in response to high glucose (20 mM) in a static glucose-stimulated insulin
      secretion assay (GSIS). In addition to an increase in eNampt secretion, exposure
      to 20 mM glucose also increased Nampt mRNA levels but not protein content. The
      secretion of eNampt was attenuated by the addition of membrane depolarization
      inhibitors, diazoxide and nifedipine. Islet-secreted eNampt showed enzymatic
      activity in a reaction with increasing production of NAD+/NADH over time. In
      summary, we show that Nampt is expressed in both exocrine and endocrine tissue
      early in life but in adulthood expression is localized to endocrine tissue.
      Enzymatically active eNampt is secreted by human islets, is regulated by glucose
      and requires membrane depolarization.

PMID- 23536824
TI  - Computational study of synthetic agonist ligands of ionotropic glutamate
      receptors.
AB  - Neurological glutamate receptors are among the most important and intensely
      studied protein ligand binding systems in humans. They are crucial for the
      functioning of the central nervous system and involved in a variety of
      pathologies. Apart from the neurotransmitter glutamate, several artificial,
      agonistic and antagonistic ligands are known. Of particular interest here are
      novel photoswitchable agonists that would open the field of optogenetics to
      glutamate receptors. The receptor proteins are complex, membrane-bound
      multidomain oligomers that undergo large scale functional conformational changes,
      making detailed studies of their atomic structure challenging. Therefore, a
      thorough understanding of the microscopic details of ligand binding and receptor
      activation remains elusive in many cases. This topic has been successfully
      addressed by theoretical studies in the past and in this paper, we present
      extensive molecular dynamics simulation and free energy calculation results on
      the binding of AMPA and an AMPA derivative, which is the basis for designing
      light-sensitive ligands. We provide a two-step model for ligand binding domain
      activation and predict binding free energies for novel compounds in good
      agreement to experimental observations.

PMID- 23536825
TI  - Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation
      and differentiation into neurons in an AD mouse model.
AB  - Neurogenesis is a life long process, but the rate of cell proliferation and
      differentiation decreases with age. In Alzheimer's patients, along with age, the
      presence of Abeta in the brain inhibits this process by reducing stem cell
      proliferation and cell differentiation. GLP-1 is a growth factor that has
      neuroprotective properties. GLP1 receptors are present on neuronal progenitor
      cells, and the GLP-1 analogue liraglutide has been shown to increase cell
      proliferation in an Alzheimer's disease (AD) mouse model. Here we investigated
      acute and chronic effects of liraglutide on progenitor cell proliferation,
      neuroblast differentiation and their subsequent differentiation into neurons in
      wild type and APP/PS-1 mice at different ages. APP/PS1 and their littermate
      controls, aged 3, 6, 12, 15 months were injected acutely or chronically with 25
      nmol/kg liraglutide. Acute treatment with liraglutide showed an increase in cell
      proliferation in APP/PS1 mice, but not in controls whereas chronic treatment
      increased cell proliferation at all ages (BrdU and Ki67 markers). Moreover,
      numbers of immature neurons (DCX) were increased in both acute and chronic
      treated animals at all ages. Most newly generated cells differentiated into
      mature neurons (NeuN marker). A significant increase was observed with
      chronically treated 6, 12, 15 month APP/PS1 and WT groups. These results
      demonstrate that liraglutide, which is currently on the market as a treatment for
      type 2 diabetes (Victoza(TM)), increases neurogenesis, which may have beneficial
      effects in neurodegenerative disorders like AD.

PMID- 23536826
TI  - The properties of genome conformation and spatial gene interaction and regulation
      networks of normal and malignant human cell types.
AB  - The spatial conformation of a genome plays an important role in the long-range
      regulation of genome-wide gene expression and methylation, but has not been
      extensively studied due to lack of genome conformation data. The recently
      developed chromosome conformation capturing techniques such as the Hi-C method
      empowered by next generation sequencing can generate unbiased, large-scale, high
      resolution chromosomal interaction (contact) data, providing an unprecedented
      opportunity to investigate the spatial structure of a genome and its applications
      in gene regulation, genomics, epigenetics, and cell biology. In this work, we
      conducted a comprehensive, large-scale computational analysis of this new stream
      of genome conformation data generated for three different human leukemia cells or
      cell lines by the Hi-C technique. We developed and applied a set of
      bioinformatics methods to reliably generate spatial chromosomal contacts from
      high-throughput sequencing data and to effectively use them to study the
      properties of the genome structures in one-dimension (1D) and two-dimension (2D).
      Our analysis demonstrates that Hi-C data can be effectively applied to study
      tissue-specific genome conformation, chromosome-chromosome interaction,
      chromosomal translocations, and spatial gene-gene interaction and regulation in a
      three-dimensional genome of primary tumor cells. Particularly, for the first
      time, we constructed genome-scale spatial gene-gene interaction network,
      transcription factor binding site (TFBS) - TFBS interaction network, and TFBS
      gene interaction network from chromosomal contact information. Remarkably, all
      these networks possess the properties of scale-free modular networks.

PMID- 23536827
TI  - Safety of pandemic (H1N1) 2009 monovalent vaccines in taiwan: a self-controlled
      case series study.
AB  - In Taiwan, new H1N1 monovalent vaccines without adjuvant and with MF59(r)
      adjuvant were used in the nationwide vaccination campaign beginning on November
      1, 2009. From November 2009 through February 2010, the authors identified
      recipients of H1N1 vaccines who were diagnosed with adverse events of special
      interest (AESIs) in a large-linked safety database, and used the self-controlled
      case series (SCCS) method to examine the risk of each AESI in the 0-42 days after
      H1N1 vaccination. Of the 3.5 million doses of H1N1 vaccines administered and
      captured in the linked database, the SCCS analysis of Guillain-Barre syndrome
      (GBS) found an incidence rate ratio of 3.81 (95% confidence interval 0.43-33.85)
      within 0-42 days after nonadjuvanted H1N1 vaccination and no cases after MF59(r)
      adjuvanted H1N1 vaccination. The risks of other AESIs were, in general, not
      increased in any of the predefined postvaccination risk periods and age groups.
      The databases and infrastructure created for H1N1 vaccine safety evaluation may
      serve as a model for safety, effectiveness and coverage studies of licensed
      vaccines in Taiwan.

PMID- 23536828
TI  - Novel frem1-related mouse phenotypes and evidence of genetic interactions with
      gata4 and slit3.
AB  - The FRAS1-related extracellular matrix 1 (FREM1) gene encodes an extracellular
      matrix protein that plays a critical role in the development of multiple organ
      systems. In humans, recessive mutations in FREM1 cause eye defects, congenital
      diaphragmatic hernia, renal anomalies and anorectal malformations including
      anteriorly placed anus. A similar constellation of findings-microphthalmia,
      cryptophthalmos, congenital diaphragmatic hernia, renal agenesis and rectal
      prolapse-have been described in FREM1-deficient mice. In this paper, we identify
      a homozygous Frem1 missense mutation (c.1687A>T, p.Ile563Phe) in an N-ethyl-N
      nitrosourea (ENU)-derived mouse strain, crf11, with microphthalmia,
      cryptophthalmos, renal agenesis and rectal prolapse. This mutation affects a
      highly conserved residue in FREM1's third CSPG domain. The p.Ile563Phe change is
      predicted to be deleterious and to cause decreased FREM1 protein stability. The
      crf11 allele also fails to complement the previously described eyes2 allele of
      Frem1 (p.Lys826*) providing further evidence that the crf11 phenotype is due to
      changes affecting Frem1 function. We then use mice bearing the crf11 and eyes2
      alleles to identify lung lobulation defects and decreased anogenital distance in
      males as novel phenotypes associated with FREM1 deficiency in mice. Due to
      phenotypic overlaps between FREM1-deficient mice and mice that are deficient for
      the retinoic acid-responsive transcription factor GATA4 and the extracellular
      matrix protein SLIT3, we also perform experiments to look for in vivo genetic
      interactions between the genes that encode these proteins. These experiments
      reveal that Frem1 interacts genetically with Gata4 in the development of lung
      lobulation defects and with Slit3 in the development of renal agenesis. These
      results demonstrate that FREM1-deficient mice faithfully recapitulate many of the
      phenotypes seen in individuals with FREM1 deficiency and that variations in GATA4
      and SLIT3 expression modulate some FREM1-related phenotypes in mice.

PMID- 23536829
TI  - Ventral tegmental area inactivation suppresses the expression of CA1 long term
      potentiation in anesthetized rat.
AB  - The hippocampus receives dopaminergic projections from the ventral tegmental area
      (VTA). Modulatory effect of dopamine on hippocampal long term potentiation (LTP)
      has been studied before, but there are conflicting results and some limitations
      in previous reports. Most of these studies show a significant effect of dopamine
      on the late phase of LTP in CA1 area of the hippocampus, while few reports show
      an effect on the early phase. Moreover, they generally manipulated dopamine
      receptors in the hippocampus and there are few studies investigating influence of
      the VTA neural activity on hippocampal LTP in the intact brain. Besides, VTA
      neurons contain other neurotransmitters such as glutamate and GABA that may
      modify the net effect of dopamine. In this study we examined the effect of VTA
      reversible inactivation on the induction and maintenance of early LTP in the CA1
      area of anesthetized rats, and also on different phases of learning of a passive
      avoidance (PA) task. We found that inactivation of the VTA by lidocaine had no
      effect on CA1 LTP induction and paired-pulse facilitation, but its inactivation
      immediately after tetanic stimulation transiently suppressed the expression of
      LTP. Blockade of the VTA 20 min after tetanic stimulation had no effect on the
      magnitude of LTP. Moreover, VTA inactivation immediately after training impaired
      memory in the passive avoidance task, while its blockade before or 20 min after
      training produced no memory deficit. It can be concluded that VTA activity has no
      effect on CA1 LTP induction and acquisition of PA task, but involves in the
      expression of LTP and PA memory consolidation.

PMID- 23536830
TI  - The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-kappaB
      p65 by preventing Ser(276) phosphorylation.
AB  - Orf virus-encoded protein 002 (ORFV002) inhibits NF-kappaB signaling pathway by
      decreasing the acetylation of NF-kappaB-p65 through interference of NF-kappaB
      p65's association with NF-kappaB p300. However, the precise mechanism of how
      ORFV002 interferes with the NF-kappaB p65/p300 association is still unknown. Due
      to similarities of the amino acid sequences of ORFV002 and the adenovirus type 12
      (Ad12) E1A protein (E1A-12), we hypothesized that the N-terminal 52 amino acids
      of ORFV002 might play an important role in this inhibition and constructed
      several in-frame fusions of ORFV002 to an enhanced green fluorescent protein
      (EGFP) reporter, including C-terminal and N-terminal deletion mutants of ORFV002.
      When the N-terminus of ORFV002 was absent, the localization of ORFV002 shifted
      mainly from the nucleus to the cytoplasm, and it's inhibition of NF-kappaB
      transactivation was lost. NF-kappaB p65 Lys(310) acetylation and Ser(276)
      phosphorylation were detected in co-transfection experiments with NF-kappaB p65
      and ORFV002 or its mutants with, or without, the N-terminal region. The results
      showed that the N-terminus of ORFV002 plays a crucial role in inhibiting both the
      acetylation and phosphorylation of NF-kappaB p65. Further investigation indicated
      that ORFV002 and its C-terminal deletion mutants interfered with NF-kappaB p65
      (Ser(276)) phosphorylation induced by mitogen- and stress-activated protein
      kinase-1 (MSK1) and the interaction between NF-kappaB p65 and MSK1. Since
      phosphorylated NF-kappaB p65 recruits transcriptional co-activators such as p300
      and CBP, we concluded that the N-terminus of ORFV002 inhibits acetylation of NF
      kappaB p65 by blocking phosphorylation of NF-kappaB p65 at Ser(276).

PMID- 23536831
TI  - Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through
      endoplasmic reticulum stress.
AB  - BACKGROUND: Casticin is one of the main active components obtained from Fructus
      Viticis and has been reported to exert anti-carcinogenic activity on a variety of
      cancer cells but the precise mechanism underlying this activity remains unclear.
      MATERIALS AND METHODS: Apoptotic activities of casticin (1.0 umol/l) and TRAIL
      (25, 50 ng/ml) alone or in combination in the gastric cancer cell lines BGC-823,
      SGC-7901 and MGC-803 were detected by the use of a cell apoptosis ELISA detection
      kit, flow cytometry (FCM) with propidium iodide (PI) staining and activities of
      caspase-3, -8 and -9 by ELISA and cleavage of polyADP-ribose polymerase (PARP)
      protein using western blot analysis. Death receptors (DR) expression levels were
      evaluated using FCM analysis and western blotting. 2', 7'-dichlorofluorescein
      diacetate (DCFH-DA) was used as a probe to measure the increase in reactive
      oxygen species (ROS) levels in cells. Multiple interventions, such as siRNA
      transfection and pharmacological inhibitors were used to explore the mechanisms
      of these actions. RESULTS: Subtoxic concentrations of casticin significantly
      potentiated TRAIL-induced cytotoxicity and apoptosis in BGC-823, SGC-7901 and MGC
      803 cells. Casticin dramatically upregulated DR5 receptor expression but had no
      effects on DR4 or decoy receptors. Deletion of DR5 by siRNA significantly reduced
      the apoptosis induced by the co-application of TRAIL and casticin. Gene silencing
      of the CCAAT/enhancer binding protein homologous protein (CHOP) and pretreatment
      with salubrinal, an endoplasmic reticulum (ER) stress inhibitor, attenuated
      casticin-induced DR5 receptor expression, and apoptosis and ROS production.
      Casticin downregulated the expression levels of the cell survival proteins cFLIP,
      Bcl-2, XIAP, and survivin. In addition, casticin also induced the expressions of
      DR5 protein in other gastric cancer cells (SGC-7901 and MGC-803).
      CONCLUSION/SIGNIFICANCE: Casticin enhances TRAIL-induced apoptosis through the
      downregulation of cell survival proteins and the upregulation of DR5 receptors
      through actions on the ROS-ER stress-CHOP pathway.

PMID- 23536832
TI  - Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel
      activity and promoting proteasome-mediated CFTR degradation.
AB  - Cyst enlargement in polycystic kidney disease (PKD) involves cAMP-activated
      proliferation of cyst-lining epithelial cells and transepithelial fluid secretion
      into the cyst lumen via cystic fibrosis transmembrane conductance regulator
      (CFTR) chloride channel. This study aimed to investigate an inhibitory effect and
      detailed mechanisms of steviol and its derivatives on cyst growth using a cyst
      model in Madin-Darby canine kidney (MDCK) cells. Among 4 steviol-related
      compounds tested, steviol was found to be the most potent at inhibiting MDCK cyst
      growth. Steviol inhibition of cyst growth was dose-dependent; steviol (100
      microM) reversibly inhibited cyst formation and cyst growth by 72.53.6% and
      38.2+/-8.5%, respectively. Steviol at doses up to 200 microM had no effect on
      MDCK cell viability, proliferation and apoptosis. However, steviol acutely
      inhibited forskolin-stimulated apical chloride current in MDCK epithelia,
      measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged
      treatment (24 h) with steviol (100 microM) also strongly inhibited forskolin
      stimulated apical chloride current, in part by reducing CFTR protein expression
      in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect
      of steviol on CFTR protein expression. Immunofluorescence studies demonstrated
      that prolonged treatment (24 h) with steviol (100 microM) markedly reduced CFTR
      expression at the plasma membrane. Taken together, the data suggest that steviol
      retards MDCK cyst progression in two ways: first by directly inhibiting CFTR
      chloride channel activity and second by reducing CFTR expression, in part, by
      promoting proteasomal degradation of CFTR. Steviol and related compounds
      therefore represent drug candidates for treatment of polycystic kidney disease.

PMID- 23536833
TI  - Effect of acute stressor and serotonin transporter genotype on amygdala first
      wave transcriptome in mice.
AB  - The most prominent brain region evaluating the significance of external stimuli
      immediately after their onset is the amygdala. Stimuli evaluated as being
      stressful actuate a number of physiological processes as an immediate stress
      response. Variation in the serotonin transporter gene has been associated with
      increased anxiety- and depression-like behavior, altered stress reactivity and
      adaptation, and pathophysiology of stress-related disorders. In this study the
      instant reactions to an acute stressor were measured in a serotonin transporter
      knockout mouse model. Mice lacking the serotonin transporter were verified to be
      more anxious than their wild-type conspecifics. Genome-wide gene expression
      changes in the amygdala were measured after the mice were subjected to control
      condition or to an acute stressor of one minute exposure to water. The dissection
      of amygdalae and stabilization of RNA was conducted within nine minutes after the
      onset of the stressor. This extremely short protocol allowed for analysis of
      first wave primary response genes, typically induced within five to ten minutes
      of stimulation, and was performed using Affymetrix GeneChip Mouse Gene 1.0 ST
      Arrays. RNA profiling revealed a largely new set of differentially expressed
      primary response genes between the conditions acute stress and control that
      differed distinctly between wild-type and knockout mice. Consequently, functional
      categorization and pathway analysis indicated genes related to neuroplasticity
      and adaptation in wild-types whereas knockouts were characterized by impaired
      plasticity and genes more related to chronic stress and pathophysiology. Our
      study therefore disclosed different coping styles dependent on serotonin
      transporter genotype even directly after the onset of stress and accentuates the
      role of the serotonergic system in processing stressors and threat in the
      amygdala. Moreover, several of the first wave primary response genes that we
      found might provide promising targets for future therapeutic interventions of
      stress-related disorders also in humans.

PMID- 23536834
TI  - Mechanomyogram for muscle function assessment: a review.
AB  - BACKGROUND: Mechanomyography (MMG) has been extensively applied in clinical and
      experimental practice to examine muscle characteristics including muscle function
      (MF), prosthesis and/or switch control, signal processing, physiological
      exercise, and medical rehabilitation. Despite several existing MMG studies of MF,
      there has not yet been a review of these. This study aimed to determine the
      current status on the use of MMG in measuring the conditions of MFs.
      METHODOLOGY/PRINCIPAL FINDINGS: Five electronic databases were extensively
      searched for potentially eligible studies published between 2003 and 2012. Two
      authors independently assessed selected articles using an MS-Word based form
      created for this review. Several domains (name of muscle, study type, sensor
      type, subject's types, muscle contraction, measured parameters, frequency range,
      hardware and software, signal processing and statistical analysis, results,
      applications, authors' conclusions and recommendations for future work) were
      extracted for further analysis. From a total of 2184 citations 119 were selected
      for full-text evaluation and 36 studies of MFs were identified. The systematic
      results find sufficient evidence that MMG may be used for assessing muscle
      fatigue, strength, and balance. This review also provides reason to believe that
      MMG may be used to examine muscle actions during movements and for monitoring
      muscle activities under various types of exercise paradigms.
      CONCLUSIONS/SIGNIFICANCE: Overall judging from the increasing number of articles
      in recent years, this review reports sufficient evidence that MMG is increasingly
      being used in different aspects of MF. Thus, MMG may be applied as a useful tool
      to examine diverse conditions of muscle activity. However, the existing studies
      which examined MMG for MFs were confined to a small sample size of healthy
      population. Therefore, future work is needed to investigate MMG, in examining MFs
      between a sufficient number of healthy subjects and neuromuscular patients.

PMID- 23536835
TI  - Single-subject grey matter graphs in Alzheimer's disease.
AB  - Coordinated patterns of cortical morphology have been described as structural
      graphs and previous research has demonstrated that properties of such graphs are
      altered in Alzheimer's disease (AD). However, it remains unknown how these
      alterations are related to cognitive deficits in individuals, as such graphs are
      restricted to group-level analysis. In the present study we investigated this
      question in single-subject grey matter networks. This new method extracts large
      scale structural graphs where nodes represent small cortical regions that are
      connected by edges when they show statistical similarity. Using this method,
      unweighted and undirected networks were extracted from T1 weighted structural
      magnetic resonance imaging scans of 38 AD patients (19 female, average age 72+/-4
      years) and 38 controls (19 females, average age 72+/-4 years). Group comparisons
      of standard graph properties were performed after correcting for grey matter
      volumetric measurements and were correlated to scores of general cognitive
      functioning. AD networks were characterised by a more random topology as
      indicated by a decreased small world coefficient (p = 3.53*10(-5)), decreased
      normalized clustering coefficient (p = 7.25*10(-6)) and decreased normalized path
      length (p = 1.91*10(-7)). Reduced normalized path length explained significantly
      (p = 0.004) more variance in measurements of general cognitive decline (32%) in
      comparison to volumetric measurements (9%). Altered path length of the
      parahippocampal gyrus, hippocampus, fusiform gyrus and precuneus showed the
      strongest relationship with cognitive decline. The present results suggest that
      single-subject grey matter graphs provide a concise quantification of cortical
      structure that has clinical value, which might be of particular importance for
      disease prognosis. These findings contribute to a better understanding of
      structural alterations and cognitive dysfunction in AD.

PMID- 23536836
TI  - Loss of pH control in Plasmodium falciparum parasites subjected to oxidative
      stress.
AB  - The intraerythrocytic malaria parasite is susceptible to oxidative stress and
      this may play a role in the mechanism of action of some antimalarial agents. Here
      we show that exposure of the intraerythrocytic malaria parasite to the oxidising
      agent hydrogen peroxide results in a fall in the intracellular ATP level and
      inhibition of the parasite's V-type H(+)-ATPase, causing a loss of pH control in
      both the parasite cytosol and the internal digestive vacuole. In contrast to the
      V-type H(+)-ATPase, the parasite's digestive vacuole H(+)-pyrophosphatase is
      insensitive to hydrogen peroxide-induced oxidative stress. This work provides
      insights into the effects of oxidative stress on the intraerythrocytic parasite,
      as well as providing an alternative possible explanation for a previous report
      that light-induced oxidative stress causes selective lysis of the parasite's
      digestive vacuole.

PMID- 23536837
TI  - Cellular catabolism of the iron-regulatory peptide hormone hepcidin.
AB  - Hepcidin, a 25-amino acid peptide hormone, is the principal regulator of plasma
      iron concentrations. Hepcidin binding to its receptor, the iron exporter
      ferroportin, induces ferroportin internalization and degradation, thus blocking
      iron efflux from cells into plasma. The aim of this study was to characterize the
      fate of hepcidin after binding to ferroportin. We show that hepcidin is taken up
      by ferroportin-expressing cells in a temperature- and pH-dependent manner, and
      degraded together with its receptor. When Texas red-labeled hepcidin (TR-Hep) was
      added to ferroportin-GFP (Fpn-GFP) expressing cells, confocal microscopy showed
      co-localization of TR-Hep with Fpn-GFP. Using flow cytometry, we showed that the
      peptide was almost completely degraded by 24 h after its addition, but that
      lysosomal inhibitors completely prevented degradation of both ferroportin and
      hepcidin. In addition, using radio-labeled hepcidin and HPLC analysis we show
      that hepcidin is not recycled, and that only degradation products are released
      from the cells. Together these results show that the hormone hepcidin and its
      receptor ferroportin are internalized together and trafficked to lysosomes where
      both are degraded.

PMID- 23536838
TI  - No evidence for prolonged visible persistence in patients with schizophrenia.
AB  - BACKGROUND: Temporal visual processing is strongly deteriorated in patients with
      schizophrenia. For example, the interval required between a visual stimulus and a
      subsequent mask has to be much longer in schizophrenic patients than in healthy
      controls. We investigated whether this deficit in temporal resolution is
      accompanied by prolonged visual persistence and/or deficient temporal precision
      (temporal asynchrony perception). METHODOLOGY/PRINCIPAL FINDINGS: We investigated
      visual persistence in three experiments. In the first, measuring temporal
      processing by so-called backward masking, prolonged visible persistence is
      supposed to decrease performance. In the second experiment, requiring temporal
      integration, prolonged persistence is supposed to improve performance. In the
      third experiment, we investigated asynchrony detection, as another measure of
      temporal resolution. Eighteen patients with schizophrenia and 15 healthy controls
      participated. Asynchrony detection was intact in the patients. However, patients'
      performance was inferior compared to healthy controls in the first two
      experiments. Hence, temporal processing in schizophrenic patients is indeed
      significantly impaired but this impairment is not caused by prolonged temporal
      integration. CONCLUSIONS/SIGNIFICANCE: Our results argue against a generally
      prolonged visual persistence in patients with schizophrenia. Together with the
      preserved ability of patients, to detect temporal asynchronies in permanently
      presented stimuli, the results indicate a more specific deficit in temporal
      processing of schizophrenic patients.

PMID- 23536839
TI  - Functional characterisation of three o-methyltransferases involved in the
      biosynthesis of phenolglycolipids in Mycobacterium tuberculosis.
AB  - Phenolic glycolipids are produced by a very limited number of slow-growing
      mycobacterial species, most of which are pathogen for humans. In Mycobacterium
      tuberculosis, the etiologic agent of tuberculosis, these molecules play a role in
      the pathogenicity by modulating the host immune response during infection. The
      major variant of phenolic glycolipids produced by M. tuberculosis, named PGL-tb,
      consists of a large lipid core terminated by a glycosylated aromatic nucleus. The
      carbohydrate part is composed of three sugar residues, two rhamnosyl units and a
      terminal fucosyl residue, which is per-O-methylated, and seems to be important
      for pathogenicity. While most of the genes responsible for the synthesis of the
      lipid core domain and the saccharide appendage of PGL-tb have been characterized,
      the enzymes involved in the O-methylation of the fucosyl residue of PGL-tb remain
      unknown. In this study we report the identification and characterization of the
      methyltransferases required for the O-methylation of the terminal fucosyl residue
      of PGL-tb. These enzymes are encoded by genes Rv2954c, Rv2955c and Rv2956.
      Mutants of M. tuberculosis harboring deletion within these genes were
      constructed. Purification and analysis of the phenolglycolipids produced by these
      strains, using a combination of mass spectrometry and NMR spectroscopy, revealed
      that Rv2954c, Rv2955c and Rv2956 encode the methyltransferases that respectively
      catalysed the O-methylation of the hydroxyl groups located at positions 3, 4 and
      2 of the terminal fucosyl residue of PGL-tb. Our data also suggest that
      methylation at these positions is a sequential process, starting with position 2,
      followed by positions 4 and 3.

PMID- 23536840
TI  - Low level of sequence diversity at merozoite surface protein-1 locus of
      Plasmodium ovale curtisi and P. ovale wallikeri from Thai isolates.
AB  - BACKGROUND: The merozoite surface protein-1 (MSP-1) is a candidate target for the
      development of blood stage vaccines against malaria. Polymorphism in MSP-1 can be
      useful as a genetic marker for strain differentiation in malarial parasites.
      Although sequence diversity in the MSP-1 locus has been extensively analyzed in
      field isolates of Plasmodium falciparum and P. vivax, the extent of variation in
      its homologues in P. ovale curtisi and P. ovale wallikeri, remains unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: Analysis of the mitochondrial cytochrome b
      sequences of 10 P. ovale isolates from symptomatic malaria patients from diverse
      endemic areas of Thailand revealed co-existence of P. ovale curtisi (n = 5) and
      P. ovale wallikeri (n = 5). Direct sequencing of the PCR-amplified products
      encompassing the entire coding region of MSP-1 of P. ovale curtisi (PocMSP-1) and
      P. ovale wallikeri (PowMSP-1) has identified 3 imperfect repeated segments in the
      former and one in the latter. Most amino acid differences between these proteins
      were located in the interspecies variable domains of malarial MSP-1. Synonymous
      nucleotide diversity (piS) exceeded nonsynonymous nucleotide diversity (piN) for
      both PocMSP-1 and PowMSP-1, albeit at a non-significant level. However, when MSP
      1 of both these species was considered together, piS was significantly greater
      than piN (p<0.0001), suggesting that purifying selection has shaped diversity at
      this locus prior to speciation. Phylogenetic analysis based on conserved domains
      has placed PocMSP-1 and PowMSP-1 in a distinct bifurcating branch that probably
      diverged from each other around 4.5 million years ago. CONCLUSION/SIGNIFICANCE:
      The MSP-1 sequences support that P. ovale curtisi and P. ovale wallikeri are
      distinct species. Both species are sympatric in Thailand. The low level of
      sequence diversity in PocMSP-1 and PowMSP-1 among Thai isolates could stem from
      persistent low prevalence of these species, limiting the chance of outcrossing at
      this locus.

PMID- 23536841
TI  - The malagarasi river does not form an absolute barrier to chimpanzee movement in
      Western Tanzania.
AB  - The Malagarasi River has long been thought to be a barrier to chimpanzee
      movements in western Tanzania. This potential geographic boundary could affect
      chimpanzee ranging behavior, population connectivity and pathogen transmission,
      and thus has implications for conservation strategies and government policy.
      Indeed, based on mitochondrial DNA sequence comparisons it was recently argued
      that chimpanzees from communities to the north and to the south of the Malagarasi
      are surprisingly distantly related, suggesting that the river prevents gene flow.
      To investigate this, we conducted a survey along the Malagarasi River. We found a
      ford comprised of rocks that researchers could cross on foot. On a trail leading
      to this ford, we collected 13 fresh fecal samples containing chimpanzee DNA, two
      of which tested positive for SIVcpz. We also found chimpanzee feces within the
      riverbed. Taken together, this evidence suggests that the Malagarasi River is not
      an absolute barrier to chimpanzee movements and communities from the areas to the
      north and south should be considered a single population. These results have
      important consequences for our understanding of gene flow, disease dynamics and
      conservation management.

PMID- 23536842
TI  - Differential distribution of genes encoding the virulence factor trans-sialidase
      along Trypanosoma cruzi Discrete typing units.
AB  - Trypanosoma cruzi the agent of Chagas disease is a monophyletic but heterogeneous
      group conformed by several Discrete Typing Units (DTUs) named TcI to TcVI
      characterized by genetic markers. The trans-sialidase (TS) is a virulence factor
      involved in cell invasion and pathogenesis that is differentially expressed in
      aggressive and less virulent parasite stocks. Genes encoding TS-related proteins
      are included in a large family divided in several groups but only one of them
      contains TS genes. Two closely related genes differing in a T/C transition encode
      the enzymatically active TS (aTS) and a lectin-like TS (iTS). We quantified the
      aTS/iTS genes from TcII and TcVI aggressive and TcI low virulent strains and
      found variable aTS number (1-32) per haploid genome. In spite of being low TS
      enzyme-expressers, TcI strains carry 28-32 aTS gene copies. The intriguing
      absence of iTS genes in TcI strains together with the presence of aTS/iTS in TcII
      and TcVI strains (virulent) were observed. Moreover, after sequencing aTS/iTS
      from 38 isolates collected along the Americas encompassing all DTUs, the
      persistent absence of the iTS gene in TcI, TcIII and TcIV was found. In addition,
      the sequence clustering together with T/C transition analysis correlated to DTUs
      of T. cruzi. The consistence of TS results with both evolutionary genome models
      proposed for T. cruzi, namely the "Two Hybridization" and the "Three Ancestor"
      was discussed and reviewed to fit present findings. Parasite stocks to attempt
      genetic KO or to assay the involvement of iTS in parasite biology and virulence
      are finally available.

PMID- 23536843
TI  - Live cell imaging of germination and outgrowth of individual bacillus subtilis
      spores; the effect of heat stress quantitatively analyzed with SporeTracker.
AB  - Spore-forming bacteria are a special problem for the food industry as some of
      them are able to survive preservation processes. Bacillus spp. spores can remain
      in a dormant, stress resistant state for a long period of time. Vegetative cells
      are formed by germination of spores followed by a more extended outgrowth phase.
      Spore germination and outgrowth progression are often very heterogeneous and
      therefore, predictions of microbial stability of food products are exceedingly
      difficult. Mechanistic details of the cause of this heterogeneity are necessary.
      In order to examine spore heterogeneity we made a novel closed air-containing
      chamber for live imaging. This chamber was used to analyze Bacillus subtilis
      spore germination, outgrowth, as well as subsequent vegetative growth. Typically,
      we examined around 90 starting spores/cells for >=4 hours per experiment. Image
      analysis with the purposely built program "SporeTracker" allows for automated
      data processing from germination to outgrowth and vegetative doubling. In order
      to check the efficiency of the chamber, growth and division of B. subtilis
      vegetative cells were monitored. The observed generation times of vegetative
      cells were comparable to those obtained in well-aerated shake flask cultures. The
      influence of a heat stress of 85 degrees C for 10 min on germination, outgrowth,
      and subsequent vegetative growth was investigated in detail. Compared to control
      samples fewer spores germinated (41.1% less) and fewer grew out (48.4% less)
      after the treatment. The heat treatment had a significant influence on the
      average time to the start of germination (increased) and the distribution and
      average of the duration of germination itself (increased). However, the
      distribution and the mean outgrowth time and the generation time of vegetative
      cells, emerging from untreated and thermally injured spores, were similar.

PMID- 23536845
TI  - Glossiness and perishable food quality: visual freshness judgment of fish eyes
      based on luminance distribution.
AB  - BACKGROUND: Previous studies have reported the effects of statistics of luminance
      distribution on visual freshness perception using pictures which included the
      degradation process of food samples. However, these studies did not examine the
      effect of individual differences between the same kinds of food. Here we
      elucidate whether luminance distribution would continue to have a significant
      effect on visual freshness perception even if visual stimuli included individual
      differences in addition to the degradation process of foods.
      METHODOLOGY/PRINCIPAL FINDINGS: We took pictures of the degradation of three
      fishes over 3.29 hours in a controlled environment, then cropped square patches
      of their eyes from the original images as visual stimuli. Eleven participants
      performed paired comparison tests judging the visual freshness of the fish eyes
      at three points of degradation. Perceived freshness scores (PFS) were calculated
      using the Bradley-Terry Model for each image. The ANOVA revealed that the PFS for
      each fish decreased as the degradation time increased; however, the differences
      in the PFS between individual fish was larger for the shorter degradation time,
      and smaller for the longer degradation time. A multiple linear regression
      analysis was conducted in order to determine the relative importance of the
      statistics of luminance distribution of the stimulus images in predicting PFS.
      The results show that standard deviation and skewness in luminance distribution
      have a significant influence on PFS. CONCLUSIONS/SIGNIFICANCE: These results show
      that even if foodstuffs contain individual differences, visual freshness
      perception and changes in luminance distribution correlate with degradation time.

PMID- 23536844
TI  - Molecular signatures in Arabidopsis thaliana in response to insect attack and
      bacterial infection.
AB  - BACKGROUND: Under the threat of global climatic change and food shortages, it is
      essential to take the initiative to obtain a comprehensive understanding of
      common and specific defence mechanisms existing in plant systems for protection
      against different types of biotic invaders. We have implemented an integrated
      approach to analyse the overall transcriptomic reprogramming and systems-level
      defence responses in the model plant species Arabidopsis thaliana (A. thaliana
      henceforth) during insect Brevicoryne brassicae (B. brassicae henceforth) and
      bacterial Pseudomonas syringae pv. tomato strain DC3000 (P. syringae henceforth)
      attacks. The main aim of this study was to identify the attacker-specific and
      general defence response signatures in A. thaliana when attacked by phloem
      feeding aphids or pathogenic bacteria. RESULTS: The obtained annotated networks
      of differentially expressed transcripts indicated that members of transcription
      factor families, such as WRKY, MYB, ERF, BHLH and bZIP, could be crucial for
      stress-specific defence regulation in Arabidopsis during aphid and P. syringae
      attack. The defence response pathways, signalling pathways and metabolic
      processes associated with aphid attack and P. syringae infection partially
      overlapped. Components of several important biosynthesis and signalling pathways,
      such as salicylic acid (SA), jasmonic acid (JA), ethylene (ET) and
      glucosinolates, were differentially affected during the two the treatments.
      Several stress-regulated transcription factors were known to be associated with
      stress-inducible microRNAs. The differentially regulated gene sets included many
      signature transcription factors, and our co-expression analysis showed that they
      were also strongly co-expressed during 69 other biotic stress experiments.
      CONCLUSIONS: Defence responses and functional networks that were unique and
      specific to aphid or P. syringae stresses were identified. Furthermore, our
      analysis revealed a probable link between biotic stress and microRNAs in
      Arabidopsis and, thus gives indicates a new direction for conducting large-scale
      targeted experiments to explore the detailed regulatory links between them. The
      presented results provide a comparative understanding of Arabidopsis - B.
      brassicae and Arabidopsis - P. syringae interactions at the transcriptomic level.

PMID- 23536846
TI  - Evolution of red algal plastid genomes: ancient architectures, introns,
      horizontal gene transfer, and taxonomic utility of plastid markers.
AB  - Red algae have the most gene-rich plastid genomes known, but despite their
      evolutionary importance these genomes remain poorly sampled. Here we characterize
      three complete and one partial plastid genome from a diverse range of
      florideophytes. By unifying annotations across all available red algal plastid
      genomes we show they all share a highly compact and slowly-evolving architecture
      and uniquely rich gene complements. Both chromosome structure and gene content
      have changed very little during red algal diversification, and suggest that
      plastid-to nucleus gene transfers have been rare. Despite their ancient
      character, however, the red algal plastids also contain several unprecedented
      features, including a group II intron in a tRNA-Met gene that encodes the first
      example of red algal plastid intron maturase - a feature uniquely shared among
      florideophytes. We also identify a rare case of a horizontally-acquired
      proteobacterial operon, and propose this operon may have been recruited for
      plastid function and potentially replaced a nucleus-encoded plastid-targeted
      paralogue. Plastid genome phylogenies yield a fully resolved tree and suggest
      that plastid DNA is a useful tool for resolving red algal relationships. Lastly,
      we estimate the evolutionary rates among more than 200 plastid genes, and assess
      their usefulness for species and subspecies taxonomy by comparison to well
      established barcoding markers such as cox1 and rbcL. Overall, these data
      demonstrates that red algal plastid genomes are easily obtainable using high
      throughput sequencing of total genomic DNA, interesting from evolutionary
      perspectives, and promising in resolving red algal relationships at
      evolutionarily-deep and species/subspecies levels.

PMID- 23536847
TI  - Cu(2+) affects amyloid-beta (1-42) aggregation by increasing peptide-peptide
      binding forces.
AB  - The link between metals, Alzheimer's disease (AD) and its implicated protein,
      amyloid-beta (Abeta), is complex and highly studied. AD is believed to occur as a
      result of the misfolding and aggregation of Abeta. The dyshomeostasis of metal
      ions and their propensity to interact with Abeta has also been implicated in AD.
      In this work, we use single molecule atomic force spectroscopy to measure the
      rupture force required to dissociate two Abeta (1-42) peptides in the presence of
      copper ions, Cu(2+). In addition, we use atomic force microscopy to resolve the
      aggregation of Abeta formed. Previous research has shown that metal ions decrease
      the lag time associated with Abeta aggregation. We show that with the addition of
      copper ions the unbinding force increases notably. This suggests that the
      reduction of lag time associated with Abeta aggregation occurs on a single
      molecule level as a result of an increase in binding forces during the very
      initial interactions between two Abeta peptides. We attribute these results to
      copper ions acting as a bridge between the two peptide molecules, increasing the
      stability of the peptide-peptide complex.

PMID- 23536848
TI  - Visual experience determines the use of external reference frames in joint action
      control.
AB  - Vision plays a crucial role in human interaction by facilitating the coordination
      of one's own actions with those of others in space and time. While previous
      findings have demonstrated that vision determines the default use of reference
      frames, little is known about the role of visual experience in coding action
      space during joint action. Here, we tested if and how visual experience
      influences the use of reference frames in joint action control. Dyads of
      congenitally-blind, blindfolded-sighted, and seeing individuals took part in an
      auditory version of the social Simon task, which required each participant to
      respond to one of two sounds presented to the left or right of both participants.
      To disentangle the contribution of external-agent-based and response-based
      reference frames during joint action, participants performed the task with their
      respective response (right) hands uncrossed or crossed over one another. Although
      the location of the auditory stimulus was completely task-irrelevant,
      participants responded overall faster when the stimulus location spatially
      corresponded to the required response side than when they were spatially non
      corresponding: a phenomenon known as the social Simon effect (SSE). In sighted
      participants, the SSE occurred irrespective of whether hands were crossed or
      uncrossed, suggesting the use of external, response-based reference frames.
      Congenitally-blind participants also showed an SSE, but only with uncrossed
      hands. We argue that congenitally-blind people use both agent-based and response
      based reference frames resulting in conflicting spatial information when hands
      are crossed and, thus, canceling out the SSE. These results imply that joint
      action control functions on the basis of external reference frames independent of
      the presence or (transient/permanent) absence of vision. However, the type of
      external reference frames used for organizing motor control in joint action seems
      to be determined by visual experience.

PMID- 23536849
TI  - A long-term low-frequency hospital outbreak of KPC-producing Klebsiella
      pneumoniae involving Intergenus plasmid diffusion and a persisting environmental
      reservoir.
AB  - BACKGROUND: To study the molecular characteristics of a long-term, low frequency
      outbreak of bla KPC-2 in a low prevalence setting involving the hospital
      environment. METHODOLOGY/PRINCIPAL FINDINGS: KPC-producing bacteria were screened
      by selective chromogenic agar and Real-Time PCR. The presence of antibiotic
      resistance genes was ascribed by PCRs and subsequent sequencing, and the KPC
      producing isolates were phylogenetically typed using PFGE and multi-locus
      sequence typing. Bla KPC-2-plasmids were identified and analysed by S1-nuclease
      PFGE hybridization and PCR based replicon typing. A ~97 kb IncFII plasmid was
      seen to carry bla KPC-2 in all of the clinical isolates, in one of the isolates
      recovered from screened patients (1/136), and in the Klebsiella pneumoniae and
      Enterobacter asburiae isolates recovered from the environment (sinks) in one
      intensive care unit. The K. pneumoniae strain ST258 was identified in 6 out of 7
      patients. An intergenus spread to E. asburiae and an interspecies spread to two
      different K. pneumoniae clones (ST27 and ST461) of the bla KPC-2 plasmid was
      discovered. K. pneumoniae ST258 and genetically related E. asburiae strains were
      found in isolates of both human and environmental origins.
      CONCLUSIONS/SIGNIFICANCE: We document a clonal transmission of the K. pneumoniae
      ST258 strain, and an intergenus plasmid diffusion of the IncFII plasmid carrying
      bla KPC-2 in this outbreak. A major reservoir in the patient population could not
      be unveiled. However, the identification of a persisting environmental reservoir
      of strains with molecular determinants linked to human isolates, suggests a
      possible role of the environment in the maintenance of this long-term outbreak.

PMID- 23536850
TI  - Some pneumococcal serotypes are more frequently associated with relapses of acute
      exacerbations in COPD patients.
AB  - OBJECTIVES: To analyze the role of the capsular type in pneumococci causing
      relapse and reinfection episodes of acute exacerbation in COPD patients. METHODS:
      A total of 79 patients with 116 recurrent episodes of acute exacerbations caused
      by S. pneumoniae were included into this study (1995-2010). A relapse episode was
      considered when two consecutive episodes were caused by the same strain
      (identical serotype and genotype); otherwise it was considered reinfection.
      Antimicrobial susceptibility testing (microdilution), serotyping (PCR, Quellung)
      and molecular typing (PFGE/MLST) were performed. RESULTS: Among 116 recurrent
      episodes, 81 (69.8%) were reinfections, caused by the acquisition of a new
      pneumococcus, and 35 (30.2%) were relapses, caused by a pre-existing strain. Four
      serotypes (9V, 19F, 15A and 11A) caused the majority (60.0%) of relapses. When
      serotypes causing relapses and reinfection were compared, only two serotypes were
      associated with relapses: 9V (OR 8.0; 95% CI, 1.34-85.59) and 19F (OR 16.1; 95%
      CI, 1.84-767.20). Pneumococci isolated from relapses were more resistant to
      antimicrobials than those isolated from the reinfection episodes: penicillin
      (74.3% vs. 34.6%, p<0.001), ciprofloxacin (25.7% vs. 9.9%, p<0.027), levofloxacin
      (22.9% vs. 7.4%, p = 0.029), and co-trimoxazole (54.3% vs. 25.9%, p<0.001).
      CONCLUSIONS: Although the acquisition of a new S. pneumoniae strain was the most
      frequent cause of recurrences, a third of the recurrent episodes were caused by a
      pre-existing strain. These relapse episodes were mainly caused by serotypes 9V
      and 19F, suggesting an important role for capsular type.

PMID- 23536851
TI  - Impact of preventive responses to epidemics in rural regions.
AB  - Various epidemics have arisen in rural locations through human-animal
      interaction, such as the H1N1 outbreak of 2009. Through collaboration with local
      government officials, we have surveyed a rural county and its communities and
      collected a dataset characterizing the rural population. From the respondents'
      answers, we build a social (face-to-face) contact network. With this network, we
      explore the potential spread of epidemics through a Susceptible-Latent-Infected
      Recovered (SLIR) disease model. We simulate an exact model of a stochastic SLIR
      Poisson process with disease parameters representing a typical influenza-like
      illness. We test vaccine distribution strategies under limited resources. We
      examine global and location-based distribution strategies, as a way to reach
      critical individuals in the rural setting. We demonstrate that locations can be
      identified through contact metrics for use in vaccination strategies to control
      contagious diseases.

PMID- 23536852
TI  - Temperate bacterial viruses as double-edged swords in bacterial warfare.
AB  - It has been argued that bacterial cells may use their temperate viruses as
      biological weapons. For instance, a few bacterial cells among a population of
      lysogenic cells could release the virus and kill susceptible non-lysogenic
      competitors, while their clone mates would be immune. Because viruses replicate
      inside their victims upon infection, this process would amplify their number in
      the arena. Sometimes, however, temperate viruses spare recipient cells from death
      by establishing themselves in a dormant state inside cells. This phenomenon is
      called lysogenization and, for some viruses such as the lambda virus, the
      probability of lysogenization increases with the multiplicity of infection.
      Therefore, the amplification of viruses leads to conflicting predictions about
      the efficacy of temperate viruses as biological weapons: amplification can
      increase the relative advantage of clone mates of lysogens but also the
      likelihood of saving susceptible cells from death, because the probability of
      lysogenization is higher. To test the usefulness of viruses as biological
      weapons, we performed competition experiments between lysogenic Escherichia coli
      cells carrying the lambda virus and susceptible lambda-free E. coli cells, either
      in a structured or unstructured habitat. In structured and sometimes in
      unstructured habitats, the lambda virus qualitatively behaved as a "replicating
      toxin". However, such toxic effect of lambda viruses ceased after a few days of
      competition. This was due to the fact that many of initially susceptible cells
      became lysogenic. Massive lysogenization of susceptible cells occurred precisely
      under the conditions where the amplification of the virus was substantial. From
      then on, these cells and their descendants became immune to the lambda virus. In
      conclusion, if at short term bacterial cells may use temperate viruses as
      biological weapons, after a few days only the classical view of temperate
      bacterial viruses as parasitic agents prevails.

PMID- 23536853
TI  - Association of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) polymorphisms in TCF7L2
      with type 2 diabetes in 9,619 Han Chinese population.
AB  - AIMS: We aimed to replicate the association of the rs290487 (IVS3C/T) and
      rs7903146 (IVS3C/T) polymorphisms of transcription factor 7-like 2 (TCF7L2) and
      type 2 diabetes mellitus (T2DM) in Han Chinese people in Henan province, China.
      METHODS: In all, 1,842 patients with T2DM and 7,777 normal glucose-tolerant
      controls underwent genotyping for the T2DM-associated variants rs7903146
      (IVS3C/T) and rs290487 (IVS3C/T). W performed a meta-analysis of the association
      of the risk alleles of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 and
      T2DM in Han Chinese by combining previous studies with the present study.
      RESULTS: We found that T2DM was associated with the CC genotype (1.364, 1.137
      1.636, p  = 0.001), the recessive model (1.457, 1.156-1.838, p  = 0.001) of
      rs290487 (IVS3C/T) and haplotype CC (1.116, 1.034-1.204, p  = 0.004) in Han
      Chinese. Moreover, our meta-analyses supported the association of the T allele
      (IVS3C/T) of rs7903146 (1.36, 1.24-1.48; p  = 6.404*10(-12)) and T2DM but not the
      C allele of rs290487 (IVS3C/T) (0.99, 0.85-1.15, p  = 0.890) in Han Chinese. We
      found no interactions between behavioral risk factors (smoking, alcohol drinking,
      and physical activity) and rs7903146 (IVS3C/T) and rs290487 (IVS3C/T)
      polymorphisms. CONCLUSIONS: The CC genotype and the recessive model of the
      variant rs290487 (IVS3C/T) and CC haplotype of rs7903146 (IVS3C/T) and rs290487
      (IVS3C/T) in TCF7L2 may be associated with T2DM in Han Chinese people in Henan
      province, China.

PMID- 23536854
TI  - Responses of soil CO2 fluxes to short-term experimental warming in alpine steppe
      ecosystem, Northern Tibet.
AB  - Soil carbon dioxide (CO2) emission is one of the largest fluxes in the global
      carbon cycle. Therefore small changes in the size of this flux can have a large
      effect on atmospheric CO2 concentrations and potentially constitute a powerful
      positive feedback to the climate system. Soil CO2 fluxes in the alpine steppe
      ecosystem of Northern Tibet and their responses to short-term experimental
      warming were investigated during the growing season in 2011. The results showed
      that the total soil CO2 emission fluxes during the entire growing season were
      55.82 and 104.31 g C m(-2) for the control and warming plots, respectively. Thus,
      the soil CO2 emission fluxes increased 86.86% with the air temperature increasing
      3.74 degrees C. Moreover, the temperature sensitivity coefficient (Q 10) of the
      control and warming plots were 2.10 and 1.41, respectively. The soil temperature
      and soil moisture could partially explain the temporal variations of soil CO2
      fluxes. The relationship between the temporal variation of soil CO2 fluxes and
      the soil temperature can be described by exponential equation. These results
      suggest that warming significantly promoted soil CO2 emission in the alpine
      steppe ecosystem of Northern Tibet and indicate that this alpine ecosystem is
      very vulnerable to climate change. In addition, soil temperature and soil
      moisture are the key factors that controls soil organic matter decomposition and
      soil CO2 emission, but temperature sensitivity significantly decreases due to the
      rise in temperature.

PMID- 23536855
TI  - Effects of hemodiafiltration and high flux hemodialysis on nerve excitability in
      end-stage kidney disease.
AB  - OBJECTIVES: Peripheral neuropathy is the most common neurological complication in
      end-stage kidney disease. While high flux hemodialysis (HFHD) and
      hemodiafiltration (HDF) have become the preferred options for extracorporeal
      dialysis therapy, the effects of these treatments on nerve excitability have not
      yet been examined. METHODS: An observational proof-of-concept study of nerve
      excitability and neuropathy was undertaken in an incident dialysis population (n
      = 17) receiving either HFHD or HDF. Nerve excitability techniques were utilised
      to assess nerve ion channel function and membrane potential, in conjunction with
      clinical assessment and standard nerve conduction studies. A mathematical model
      of axonal excitability was used to investigate the underlying basis of the
      observed changes. Nerve excitability was recorded from the median nerve, before,
      during and after a single dialysis session and correlated with corresponding
      biochemical markers. Differences in nerve excitability were compared to normal
      controls with longitudinal follow-up over an 18 month period. RESULTS: Nerve
      excitability was performed in patient cohorts treated with either HFHD (n = 9) or
      online HDF (n = 8), with similar neuropathy status. Nerve excitability measures
      in HDF-treated patients were significantly closer to normal values compared to
      HFHD patients obtained over the course of a dialysis session (p<0.05).
      Longitudinal studies revealed stability of nerve excitability findings, and thus
      maintenance of improved nerve function in the HDF group. CONCLUSIONS: This study
      has provided evidence that nerve excitability in HDF-treated patients is
      significantly closer to normal values prior to dialysis, across a single dialysis
      session and at longitudinal follow-up. These findings offer promise for the
      management of neuropathy in ESKD and should be confirmed in randomised trials.

PMID- 23536856
TI  - NR5A2 regulates Lhb and Fshb transcription in gonadotrope-like cells in vitro,
      but is dispensable for gonadotropin synthesis and fertility in vivo.
AB  - Successful mammalian reproduction depends on proper synthesis of the pituitary
      derived glycoprotein hormones, luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH). Several transcription factors cooperate to activate cell-specific
      and hormone-regulated expression of the gonadotropin beta subunits (Lhb and
      Fshb). Among these, NR5A1 (steroidogenic factor 1; SF1) has been shown to
      directly bind to the Lhb promoter, mediate basal and gonadotropin-releasing
      hormone (GnRH)-stimulated Lhb transcription, and possibly directly regulate Fshb
      expression. Recently, the closely-related NR5A2 was shown to activate the rat Lhb
      promoter in vitro. Here, we further characterized the role of NR5A2 in regulating
      gonadotropin synthesis. Ectopically expressed NR5A2 directly activated the murine
      Lhb promoter in a manner identical to that of NR5A1, whereas neither factor
      activated the murine Fshb promoter. In LbetaT2 gonadotrope-like cells, depletion
      of endogenous NR5A1 or NR5A2 impaired basal and GnRH-stimulated Lhb and Fshb
      transcription. To analyze the physiological role of NR5A2 in gonadotropes in
      vivo, we generated mice with a gonadotrope-specific deletion of Nr5a2. In
      contrast with our in vitro data, these mice had normal pituitary Lhb and Fshb
      expression and intact fertility. Together, our data establish that NR5A2 can act
      in a non-redundant manner to regulate Lhb and Fshb transcription in vitro, but is
      dispensable in vivo.

PMID- 23536857
TI  - Genetic variants of MICB and PLCE1 and associations with non-severe dengue.
AB  - BACKGROUND: A recent genome-wide association study (GWAS) identified
      susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1
      rs3740360. The aim of this study was to define the extent to which MICB
      (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical
      phenotypes of pediatric and adult dengue. METHODS: 3961 laboratory-confirmed
      dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1
      rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were
      calculated for each patient cohort. Pooled analyses were performed for adults and
      paediatrics respectively using a fixed effects model. RESULTS: Pooled analysis of
      the paediatric and adult cohorts indicated a significant association between MICB
      rs3132468 and dengue cases without shock (OR  =  1.15; 95%CI: 1.07 - 1.24; P  = 
      0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a
      significant association between dengue cases without shock and PLCE1 rs3740360
      (OR  =  0.92; 95%CI: 0.85 - 0.99; P  =  0.018). We also note significant
      association between both SNPs (OR  =  1.48; P  =  0.0075 for MICB rs3132468 and
      OR  =  0.75, P  =  0.041 for PLCE1 rs3740360) and dengue in infants. DISCUSSION:
      This study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes
      are not only associated with DSS, but are also associated with less severe
      clinical phenotypes of dengue, as well as with dengue in infants. These findings
      have implications for our understanding of dengue pathogenesis.

PMID- 23536858
TI  - Waist circumference, not body mass index, is associated with renal function
      decline in korean population: hallym aging study.
AB  - BACKGROUND: Prospective investigation of obesity and renal function decline in
      Asia is sparse. We examined the associations of body mass index (BMI) and waist
      circumference (WC) with renal function decline in a prospective study of Korean
      population. METHODS: A total of 454 participants who had baseline estimated
      glomerular filtration rate (eGFR) levels of more than 60 mL/min/1.73 m(2) in
      Hallym Aging Study (HAS) were included and followed for 6 years. Renal function
      decline was defined as follows: (1) an eGFR decline >=3 mL/min/1.73 m(2)/year (n
      = 82 cases); (2) an eGFR decrease of 20% or greater (n = 87 cases) at follow-up;
      (3) an eGFR decrease of 20% greater at follow-up or eGFR decline >=3 mL/min/1.73
      m(2)/year (n = 91 cases); and (4) an eGFR <60 mL/min/1.73 m(2) at follow-up (n =
      54 cases). eGFR was determined based on the Modification of Diet in Renal Disease
      (MDRD) Study equation. Multivariate logistic regression model was used to
      determine the association between obesity and renal function decline. RESULTS: We
      found that central obesity was associated with faster renal function decline.
      Comparing WC of >95 cm in men or >90 cm in women with <=90 cm in men or <=85 cm
      in women, ORs (95% CIs) ranged from 2.31 (1.14-4.69) to 2.78 (1.19-6.50) for the
      4 definitions of renal function decline (all p-values for trend <0.05). Waist-to
      hip ratio (WHR) and waist-to-height ratio (WHtR) also was associated with renal
      function decline. There was no significant association of BMI with renal function
      decline. CONCLUSIONS: Central obesity, but not BMI, is associated with faster
      renal function decline in Korean population. Our results provide important
      evidence that simple measurement of central fat deposition rather than BMI could
      predict decline in renal function in Korean population.

PMID- 23536859
TI  - The evolution and diversity of SALMFamide neuropeptides.
AB  - The SALMFamides are a family of neuropeptides that act as muscle relaxants in
      echinoderms. Two types of SALMFamides have been identified: L-type (e.g. the
      starfish neuropeptides S1 and S2) with the C-terminal motif LxFamide (x is
      variable) and F-type with the C-terminal motif FxFamide. In the sea urchin
      Strongylocentrotus purpuratus (class Echinoidea) there are two SALMFamide genes,
      one encoding L-type SALMFamides and a second encoding F-type SALMFamides, but
      hitherto it was not known if this applies to other echinoderms. Here we report
      the identification of SALMFamide genes in the sea cucumber Apostichopus japonicus
      (class Holothuroidea) and the starfish Patiria miniata (class Asteroidea). In
      both species there are two SALMFamide genes: one gene encoding L-type SALMFamides
      (e.g. S1 in P. miniata) and a second gene encoding F-type SALMFamides plus one or
      more L-type SALMFamides (e.g. S2-like peptide in P. miniata). Thus, the ancestry
      of the two SALMFamide gene types traces back to the common ancestor of echinoids,
      holothurians and asteroids, although it is not clear if the occurrence of L-type
      peptides in F-type SALMFamide precursors is an ancestral or derived character.
      The gene sequences also reveal a remarkable diversity of SALMFamide
      neuropeptides. Originally just two peptides (S1 and S2) were isolated from
      starfish but now we find that in P. miniata, for example, there are sixteen
      putative SALMFamide neuropeptides. Thus, the SALMFamides would be a good model
      system for experimental analysis of the physiological significance of
      neuropeptide "cocktails" derived from the same precursor protein.

PMID- 23536860
TI  - Mate-searching behaviour of common and rare wasps and the implications for pollen
      movement of the sexually deceptive orchids they pollinate.
AB  - Pollinator behaviour directly affects patterns of pollen movement and outcrossing
      rates in plants. In orchids pollinated by sexual deception of insects, patterns
      of pollen movement are primarily determined by the mate-searching behaviour of
      the deceived males. Here, using a capture-mark-recapture study (CMR) and dietary
      analysis, we compare mate-searching behaviour in relation to local abundance of
      two pollinator species and explore the implications for pollen movement in
      sexually deceptive Drakaea (Orchidaceae). Drakaea are pollinated solely by the
      sexual deception of male thynnine wasps. The rare Drakaea elastica and widespread
      D. livida occur sympatrically and are pollinated by the rare but locally common
      Zaspilothynnus gilesi, and the widespread and abundant Z. nigripes, respectively.
      Local abundance was significantly different with Z. nigripes twice as abundant as
      Z. gilesi. For the 653 marked wasps, there was no significant difference in
      median movement distance between Z. gilesi and Z. nigripes. However, the maximum
      movement distance was twice as high for Z. gilesi (556 m) compared with Z.
      nigripes (267 m). This is up to three times greater than previously reported for
      thynnines in CMR studies. Recapture rates were six times higher in Z. gilesi
      (57%) compared to Z. nigripes (9%). Pollen loads and wasp longevity were similar,
      suggesting that this difference in recapture rate arises due to differences in
      the number of males moving at a scale >500 m rather than through diet or
      mortality. Differences in the frequency of longer movements may arise due to
      variation in the spatial distribution of the wingless females. We predict that
      pollen movement will largely be restricted to within populations of Drakaea (<500
      m), with few movements between populations (>500 m).

PMID- 23536861
TI  - Function-related positioning of the type II secretion ATPase of Xanthomonas
      campestris pv. campestris.
AB  - Gram-negative bacteria use the type II secretion (T2S) system to secrete
      exoproteins for attacking animal or plant cells or to obtain nutrients from the
      environment. The system is unique in helping folded proteins traverse the outer
      membrane. The secretion machine comprises multiple proteins spanning the cell
      envelope and a cytoplasmic ATPase. Activity of the ATPase, when copurified with
      the cytoplasmic domain of an interactive ATPase partner, is stimulated by an
      acidic phospholipid, suggesting the membrane-associated ATPase is actively
      engaged in secretion. How the stimulated ATPase activity is terminated when
      secretion is complete is unclear. We fused the T2S ATPase of Xanthomonas
      campestris pv. campestris, the causal agent of black rot in the crucifers, with
      fluorescent protein and found that the ATPase in secretion-proficient cells was
      mainly diffused in cytoplasm. Focal spots at the cell periphery were detectable
      only in a few cells. The discrete foci were augmented in abundance and intensity
      when the secretion channel was depleted and the exoprotein overproduced. The foci
      abundance was inversely related to secretion efficiency of the secretion channel.
      Restored function of the secretion channel paralleled reduced ATPase foci
      abundance. The ATPase foci colocalized with the secretion channel. The ATPase may
      be transiently associated with the T2S machine by alternating between a
      cytoplasmic and a machine-associated state in a secretion-dependent manner. This
      provides a logical means for terminating the ATPase activity when secretion is
      completed. Function-related dynamic assembly may be the essence of the T2S
      machine.

PMID- 23536863
TI  - Atlantic origin of the arctic biota? Evidence from phylogenetic and
      biogeographical analysis of the cheilostome bryozoan genus pseudoflustra.
AB  - The intricate geological evolution of the Arctic Ocean is paralleled by
      complexities in the biogeographical and phylogenetical histories of the Arctic
      biota, including bryozoans. Here we present revised taxonomic descriptions for
      all known species of the bryozoan genus Pseudoflustra, and use the present-day
      distributions and phylogenetic relationships between these species to infer the
      historical biogeography of the genus. Nine species belonging to the genus
      Pseudoflustra are recognized in the Arctic and North Atlantic. One new species,
      previously identified as Ichthyaria aviculata, is described as Pseudoflustra
      radeki sp. nov. Another species, previously assigned to Smittoidea as S.
      perrieri, is transferred to Pseudoflustra. Biogeographical analysis of
      Pseudoflustra reveals that species distributions mostly match current patterns
      pertaining in the North Atlantic and Arctic Ocean. Distributions were probably
      shaped by recent geological history as present-day current directions in the
      Arctic Ocean are believed to have been similar for at least the last 120 000
      years. Phylogenetic analysis of Pseudoflustra places the five Arctic-North
      Atlantic species in a clade crownward of a paraphyletic grouping of North
      Atlantic species. Given that the Arctic Ocean was fully glaciated until 18 000
      years, the most likely explanation for this phylogeographical pattern is that
      species of Pseudoflustra colonized the Arctic relatively recently from North
      Atlantic sources. However, a fuller understanding of the origin of Pseudoflustra
      in the Arctic will require molecular and fossil data, neither of which are
      currently available.

PMID- 23536862
TI  - Proteasome-mediated proteolysis of SRSF5 splicing factor intriguingly co-occurs
      with SRSF5 mRNA upregulation during late erythroid differentiation.
AB  - SR proteins exhibit diverse functions ranging from their role in constitutive and
      alternative splicing, to virtually all aspects of mRNA metabolism. These findings
      have attracted growing interest in deciphering the regulatory mechanisms that
      control the tissue-specific expression of these SR proteins. In this study, we
      show that SRSF5 protein decreases drastically during erythroid cell
      differentiation, contrasting with a concomitant upregulation of SRSF5 mRNA level.
      Proteasome chemical inhibition provided strong evidence that endogenous SRSF5
      protein, as well as protein deriving from stably transfected SRSF5 cDNA, are both
      targeted to proteolysis as the cells undergo terminal differentiation.
      Consistently, functional experiments show that overexpression of SRSF5 enhances a
      specific endogenous pre-mRNA splicing event in proliferating cells, but not in
      differentiating cells, due to proteasome-mediated targeting of both endogenous
      and transfection-derived SRSF5. Further investigation of the relationship between
      SRSF5 structure and its post-translation regulation and function, suggested that
      the RNA recognition motifs of SRSF5 are sufficient to activate pre-mRNA splicing,
      whereas proteasome-mediated proteolysis of SRSF5 requires the presence of the C
      terminal RS domain of the protein. Phosphorylation of SR proteins is a key post
      translation regulation that promotes their activity and subcellular availability.
      We here show that inhibition of the CDC2-like kinase (CLK) family and mutation of
      the AKT phosphorylation site Ser86 on SRSF5, have no effect on SRSF5 stability.
      We reasoned that at least AKT and CLK signaling pathways are not involved in
      proteasome-induced turnover of SRSF5 during late erythroid development.

PMID- 23536864
TI  - Waist circumference independently associates with the risk of insulin resistance
      and type 2 diabetes in mexican american families.
AB  - OBJECTIVE: In spite of the growing recognition of the specific association of
      waist circumference (WC) with type 2 diabetes (T2D) and insulin resistance (IR),
      current guidelines still use body mass index (BMI) as a tool of choice. Our
      objective was to determine whether WC is a better T2D predictor than BMI in
      family-based settings. RESEARCH DESIGN AND METHODS: Using prospectively collected
      data on 808 individuals from 42 extended Mexican American families representing
      7617.92 person-years follow-up, we examined the performance of WC and BMI as
      predictors of cumulative and incident risk of T2D. We used robust statistical
      methods that accounted for the kinships and included polygenic models, discrete
      trait modeling, Akaike information criterion, odds ratio (OR), relative risk (RR)
      and Kullback-Leibler R(2). SOLAR software was used to conduct all the data
      analyses. RESULTS: We found that in multivariate polygenic models, WC was an
      independent predictor of cumulative (OR = 2.76, p = 0.0002) and future risk of
      T2D (RR = 2.15, p = 3.56*10(-9)) and outperformed BMI when compared in a head-to
      head fashion. High WC (>=94.65 cm after adjusting for age and sex) was also
      associated with high fasting glucose, insulin and triglyceride levels and low
      high-density lipoprotein levels indicating a potential association with IR.
      Moreover, WC was specifically and significantly associated with insulin resistant
      T2D (OR = 4.83, p = 1.01*10(-13)). CONCLUSIONS: Our results demonstrate the value
      of using WC as a screening tool of choice for future risk of T2D in Mexican
      American families. Also, WC is specifically associated with insulin resistant
      T2D.

PMID- 23536865
TI  - Reversal of succinylcholine induced apnea with an organophosphate scavenging
      recombinant butyrylcholinesterase.
AB  - BACKGROUND: Concerns about the safety of paralytics such as succinylcholine to
      facilitate endotracheal intubation limit their use in prehospital and emergency
      department settings. The ability to rapidly reverse paralysis and restore
      respiratory drive would increase the safety margin of an agent, thus permitting
      the pursuit of alternative intubation strategies. In particular, patients who
      carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme
      responsible for succinylcholine hydrolysis, are susceptible to succinylcholine
      induced apnea, which manifests as paralysis, lasting hours beyond the normally
      brief half-life of succinylcholine. We hypothesized that intravenous
      administration of plant-derived recombinant BChE, which also prevents mortality
      in nerve agent poisoning, would rapidly reverse the effects of succinylcholine.
      METHODS: Recombinant butyrylcholinesterase was produced in transgenic plants and
      purified. Further analysis involved murine and guinea pig models of
      succinylcholine toxicity. Animals were treated with lethal and sublethal doses of
      succinylcholine followed by administration of butyrylcholinesterase or vehicle.
      In both animal models vital signs and overall survival at specified intervals
      post succinylcholine administration were assessed. RESULTS: Purified plant
      derived recombinant human butyrylcholinesterase can hydrolyze succinylcholine in
      vitro. Challenge of mice with an LD100 of succinylcholine followed by BChE
      administration resulted in complete prevention of respiratory inhibition and
      concomitant mortality. Furthermore, experiments in symptomatic guinea pigs
      demonstrated extremely rapid succinylcholine detoxification with complete
      amelioration of symptoms and no apparent complications. CONCLUSIONS: Recombinant
      plant-derived butyrylcholinesterase was capable of counteracting and reversing
      apnea in two complementary models of lethal succinylcholine toxicity, completely
      preventing mortality. This study of a protein antidote validates the feasibility
      of protection and treatment of overdose from succinylcholine as well as other
      biologically active butyrylcholinesterase substrates.

PMID- 23536866
TI  - Norisoboldine suppresses osteoclast differentiation through preventing the
      accumulation of TRAF6-TAK1 complexes and activation of MAPKs/NF-kappaB/c
      Fos/NFATc1 Pathways.
AB  - Norisoboldine (NOR) is the main alkaloid constituent in the dry root of Lindera
      aggregata (Sims) Kosterm. (L. strychnifolia Vill.). As reported previously,
      orally administered NOR displayed a robust inhibition of joint bone destruction
      present in both mouse collagen-induced arthritis and rat adjuvant-induced
      arthritis with lower efficacious doses than that required for ameliorating
      systemic inflammation. This attracted us to assess the effects of NOR on
      differentiation and function of osteoclasts, primary effector cells for
      inflammatory bone destruction, to get insight into its anti-rheumatoid arthritis
      mechanisms. Both RAW264.7 cells and mouse bone marrow-derived macrophages (BMMs)
      were stimulated with RANKL (100 ng/mL) to establish osteoclast differentiation
      models. ELISA, RT-PCR, gelatin zymography, western blotting, immunoprecipitation
      and EMSA were used to reveal related signalling pathways. NOR (10 and 30 uM),
      without significant cytotoxicity, showed significant reduction of the number of
      osteoclasts and the resorption pit areas, and it targeted osteoclast
      differentiation at the early stage. In conjunction with the anti-resorption
      effect of NOR, mRNA levels of cathepsin K and MMP-9 were decreased, and the
      activity of MMP-9 was attenuated. Furthermore, our mechanistic studies indicated
      that NOR obviously suppressed the ubiquitination of TRAF6, the accumulation of
      TRAF6-TAK1 complexes and the activation of ERK and p38 MAPK, and reduced the
      nuclear translocation of NF-kappaB-p65 and DNA-binding activity of NF-kappaB.
      However, NOR had little effect on expressions of TRAF6 or the phosphorylation and
      degradation of IkappaBalpha. Moreover, NOR markedly inhibited expressions of
      transcription factor NFATc1, but not c-Fos. Intriguingly, the subsequent nuclear
      translocations of c-Fos and NFATc1 were substantially down-regulated. Hence, we
      demonstrated for the first time that preventing the differentiation and function
      of osteoclasts at the early stage was an important anti-bone destruction
      mechanism of NOR, which might be attributed to inhibition of ubiquitination of
      TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of MAPKs/NF
      kappaB/c-Fos/NFATc1 pathways.

PMID- 23536867
TI  - Immunomodulatory effects of Escherichia coli ATCC 25922 on allergic airway
      inflammation in a mouse model.
AB  - BACKGROUND: Hygiene hypothesis demonstrates that the lack of microbial exposure
      would promote the development of allergic airway disease (AAD). Therefore, the
      gut microbiota, including Escherichia coli (E. coli), would probably offer a
      potential strategy for AAD. OBJECTIVE: To investigate whether E. coli infection
      is able to suppress the induction of AAD and to elucidate the underlying
      mechanisms. METHODS: Nonpathogenic E. coli ATCC 25922 was infected by gavage
      before AAD phase in three patterns: 10(8) or 10(6) CFU in neonates or 10(8) CFU
      in adults. Then mice were sensitized and challenged with ovalbumin (OVA) to
      induce allergic inflammation in both the upper and lower airways. Hallmarks of
      AAD, in terms of eosinophil infiltration and goblet cell metaplasia in
      subepithelial mucosa, Th2 skewing of the immune response, and levels of T
      regulate cells (Tregs), were examined by histological analysis, ELISA, and flow
      cytometry, respectively. RESULTS: E. coli, especially neonatally infected with an
      optimal dose, attenuated allergic responses, including a decrease in nasal
      rubbing and sneezing, a reduction in eosinophil inflammation and goblet cell
      metaplasia in subepithelial mucosa, decreased serum levels of OVA-specific IgE,
      and reduced Th2 (IL-4) cytokines. In contrast, this effect came with an increase
      of Th1 (IFN-r and IL-2) cytokines, and an enhancement of IL-10-secreting Tregs in
      paratracheal lymph nodes (PTLN). CONCLUSION: E. coli suppresses allergic
      responses in mice, probably via a shift from Th1 to Th2 and/or induction of
      Tregs. Moreover, this infection is age- and dose-dependent, which may open up
      novel possibilities for new therapeutic interventions.

PMID- 23536868
TI  - Ascertaining an appropriate diagnostic algorithm using EGFR mutation-specific
      antibodies to detect EGFR status in non-small-cell lung cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation status is the most
      valuable indicator in the screening of non-small-cell lung cancer (NSCLC)
      patients for tyrosine kinase inhibitor (TKI) therapy. Accurate, rapid and
      economical methods of detecting EGFR mutations have become important. The use of
      two mutation-specific antibodies targeting the delE746-A750 mutation in exon 19
      and L858R mutation in exon 21 makes this task possible, but the lack of
      consensually acceptable criteria for positive results limits the application of
      this antibody based mutation detection. METHODS: We collected 399 specimens from
      NSCLC patients (145 resection specimens, 220 biopsy specimens, and 34 cytology
      specimens) whose EGFR mutation status had been detected by TaqMan PCR assay.
      Immunohistochemical (IHC) analyses using EGFR mutation-specific antibodies were
      employed for all samples. After staining and scoring, the sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      were calculated in accordance with different levels of positive grades in
      comparison with the results of PCR-based assay. RESULTS: In IHC-based analyses,
      144 cases were scored 0, 104 cases were scored 1+, 103 cases were scored 2+, and
      48 cases were scored 3+. With the molecular-based results were set as the "gold
      standard", the prevalence of mutation was 6.94% (10/144), 23.08% (24/104), 67.96%
      (70/103) and 100% (48/48), respectively, for samples with scores 0, 1+, 2+ and
      3+. When score 3+ was considered positive, the specificity and PPV were 100%; if
      only score 0 was considered negative, 93.06% NPV was obtained. CONCLUSION:
      Patients with score 3+ have a perfect PPV (100%), and may accept TKI treatment
      directly without any molecular-based assays. Patients with score 0 had high NPV
      (93.06%), which could reach 97.22% when the detection of total EGFR was applied.
      However, samples with score 1+ or 2+ are unreliable and need further verification
      of EGFR mutation status by molecular-based assays.

PMID- 23536869
TI  - Separate origins of ice-binding proteins in antarctic chlamydomonas species.
AB  - The green alga Chlamydomonas raudensis is an important primary producer in a
      number of ice-covered lakes and ponds in Antarctica. A C. raudensis isolate
      (UWO241) from Lake Bonney in the McMurdo Dry Valleys, like many other Antarctic
      algae, was found to secrete ice-binding proteins (IBPs), which appear to be
      essential for survival in icy environments. The IBPs of several Antarctic algae
      (diatoms, a prymesiophyte, and a prasinophyte) are similar to each other (here
      designated as type I IBPs) and have been proposed to have bacterial origins.
      Other IBPs (type II IBPs) that bear no resemblance to type I IBPs, have been
      found in the Antarctic Chlamydomonas sp. CCMP681, a putative snow alga, raising
      the possibility that chlamydomonad IBPs developed separately from the IBPs of
      other algae. To test this idea, we obtained the IBP sequences of C. raudensis
      UWO241 by sequencing the transcriptome. A large number of transcripts revealed no
      sequences resembling type II IBPs. Instead, many isoforms resembling type I IBPs
      were found, and these most closely matched a hypothetical protein from the
      bacterium Stigmatella aurantiaca. The sequences were confirmed to encode IBPs by
      the activity of a recombinant protein and by the matching of predicted and
      observed isoelectric points and molecular weights. Furthermore, a mesophilic
      sister species, C. raudensis SAG49.72, showed no ice-binding activity or PCR
      products from UWO241 IBP primers. These results confirm that algal IBPs are
      required for survival in icy habitats and demonstrate that they have diverse
      origins that are unrelated to the taxonomic positions of the algae. Last, we show
      that the C. raudensis UWO241 IBPs can change the structure of ice in a way that
      could increase the survivability of cells trapped in the ice.

PMID- 23536870
TI  - Expression and pharmacology of endogenous Cav channels in SH-SY5Y human
      neuroblastoma cells.
AB  - SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the
      mechanisms underlying neurotransmission and nociception. These cells are derived
      from human sympathetic neuronal tissue and thus, express a number of the Cav
      channel subtypes essential for regulation of important physiological functions,
      such as heart contraction and nociception, including the clinically validated
      pain target Cav2.2. We have detected mRNA transcripts for a range of endogenous
      expressed subtypes Cav1.3, Cav2.2 (including two Cav1.3, and three Cav2.2 splice
      variant isoforms) and Cav3.1 in SH-SY5Y cells; as well as Cav auxiliary subunits
      alpha2delta1-3, beta1, beta3, beta4, gamma1, gamma4-5, and gamma7. Both high- and
      low-voltage activated Cav channels generated calcium signals in SH-SY5Y cells.
      Pharmacological characterisation using omega-conotoxins CVID and MVIIA revealed
      significantly (~ 10-fold) higher affinity at human versus rat Cav2.2, while GVIA,
      which interacts with Cav2.2 through a distinct pharmacophore had similar affinity
      for both species. CVID, GVIA and MVIIA affinity was higher for SH-SY5Y membranes
      vs whole cells in the binding assays and functional assays, suggesting auxiliary
      subunits expressed endogenously in native systems can strongly influence Cav2.2
      channels pharmacology. These results may have implications for strategies used to
      identify therapeutic leads at Cav2.2 channels.

PMID- 23536871
TI  - Modeling and mapping of atmospheric mercury deposition in adirondack park, new
      york.
AB  - The Adirondacks of New York State, USA is a region that is sensitive to
      atmospheric mercury (Hg) deposition. In this study, we estimated atmospheric Hg
      deposition to the Adirondacks using a new scheme that combined numerical modeling
      and limited experimental data. The majority of the land cover in the Adirondacks
      is forested with 47% of the total area deciduous, 20% coniferous and 10% mixed.
      We used litterfall plus throughfall deposition as the total atmospheric Hg
      deposition to coniferous and deciduous forests during the leaf-on period, and wet
      Hg deposition plus modeled atmospheric dry Hg deposition as the total Hg
      deposition to the deciduous forest during the leaf-off period and for the non
      forested areas year-around. To estimate atmospheric dry Hg deposition we used the
      Big Leaf model. The average atmospheric Hg deposition to the Adirondacks was
      estimated as 17.4 [Formula: see text]g m[Formula: see text] yr[Formula: see text]
      with a range of -3.7-46.0 [Formula: see text]g m[Formula: see text] yr[Formula:
      see text]. Atmospheric Hg dry deposition (370 kg yr[Formula: see text]) was found
      to be more important than wet deposition (210 kg yr[Formula: see text]) to the
      entire Adirondacks (2.4 million ha). The spatial pattern showed a large variation
      in atmospheric Hg deposition with scattered areas in the eastern Adirondacks
      having total Hg deposition greater than 30 MUg m(-2) yr(-1), while the
      southwestern and the northern areas received Hg deposition ranging from 25-30 MUg
      m(-2) yr(-1).

PMID- 23536872
TI  - Maternal effects in relation to helper presence in the cooperatively breeding
      sociable weaver.
AB  - In egg laying species, breeding females may adjust the allocation of nutrients or
      other substances into eggs in order to maximise offspring or maternal fitness.
      Cooperatively breeding species offer a particularly interesting context in which
      to study maternal allocation because helpers create predictably improved
      conditions during offspring development. Some recent studies on cooperative
      species showed that females assisted by helpers produced smaller eggs, as the
      additional food brought by the helpers appeared to compensate for this reduction
      in egg size. However, it remains unclear how common this effect might be. Also
      currently unknown is whether females change egg composition when assisted by
      helpers. This effect is predicted by current maternal allocation theory, but has
      not been previously investigated. We studied egg mass and contents in sociable
      weavers (Philetairus socius). We found that egg mass decreased with group size,
      while fledgling mass did not vary, suggesting that helpers may compensate for the
      reduced investment in eggs. We found no differences in eggs' carotenoid contents,
      but females assisted by helpers produced eggs with lower hormonal content,
      specifically testosterone, androstenedione (A4) and corticosterone levels. Taken
      together, these results suggest that the environment created by helpers can
      influence maternal allocation and potentially offspring phenotypes.

PMID- 23536873
TI  - Up-regulation of hepatoma-derived growth factor facilitates tumor progression in
      malignant melanoma [corrected].
AB  - Cutaneous malignant melanoma is the fastest increasing malignancy in humans.
      Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from
      human hepatoma cell line. HDGF overexpression is correlated with poor prognosis
      in various types of cancer including melanoma. However, the underlying mechanism
      of HDGF overexpression in developing melanoma remains unclear. In this study,
      human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of
      HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less.
      Exogenous application of HDGF stimulated colony formation and invasion of human
      melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion
      and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted
      opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and
      metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were
      performed by manipulating the gene expression of HDGF in melanoma cells. It was
      found that mice injected with HDGF-overexpressing melanoma cells had greater
      tumour growth and higher metastatic capability. In contrast, mice implanted with
      HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis.
      Histological analysis of excised tumors revealed higher degree of cell
      proliferation and neovascularization in HDGF-overexpressing melanoma. The present
      study provides evidence that HDGF promotes tumor progression of melanoma and
      targeting HDGF may constitute a novel strategy for the treatment of melanoma.

PMID- 23536874
TI  - Can you catch a liar? How negative emotions affect brain responses when lying or
      telling the truth.
AB  - The capacity to deceive others is a complex mental skill that requires the
      ability to suppress truthful information. The polygraph is widely used in
      countries such as the USA to detect deception. However, little is known about the
      effects of emotional processes (such as the fear of being found guilty despite
      being innocent) on the physiological responses that are used to detect lies. The
      aim of this study was to investigate the time course and neural correlates of
      untruthful behavior by analyzing electrocortical indexes in response to visually
      presented neutral and affective questions. Affective questions included sexual,
      shameful or disgusting topics. A total of 296 questions that were inherently true
      or false were presented to 25 subjects while ERPs were recorded from 128 scalp
      sites. Subjects were asked to lie on half of the questions and to answer
      truthfully on the remaining half. Behavioral and ERP responses indicated an
      increased need for executive control functions, namely working memory, inhibition
      and task switching processes, during deceptive responses. Deceptive responses
      also elicited a more negative N400 over the prefrontal areas and a smaller late
      positivity (LP 550-750 ms) over the prefrontal and frontal areas. However, a
      reduction in LP amplitude was also elicited by truthful affective responses. The
      failure to observe a difference in LP responses across conditions likely results
      from emotional interference. A swLORETA inverse solution was computed on the N400
      amplitude (300-400 ms) for the dishonest - honest contrast. These results showed
      the activation of the superior, medial, middle and inferior frontal gyri (BA9,
      11, 47) and the anterior cingulate cortex during deceptive responses. Our results
      conclude that the N400 amplitude is a reliable neural marker of deception.

PMID- 23536875
TI  - Epidemiology and evolution of rotaviruses and noroviruses from an archival WHO
      Global Study in Children (1976-79) with implications for vaccine design.
AB  - Prompted by the discovery of new gastrointestinal viruses, the NIH, NIAID and WHO
      investigated the etiology of acute diarrhea that occurred from 1976-1979 in a
      global cohort of infants and young children. Rotaviruses were found to be major
      pathogens worldwide, whereas the Norwalk virus could not be detected using a
      radioimmunoassay. The aim of this study is to re-evaluate the role and diversity
      of rotaviruses and noroviruses in the original cohort using more sensitive
      current technologies. Stools collected from Asia, Africa, and South America (n =
      485) were evaluated for viral genotypes by RT-PCR and sequencing. Rotaviruses
      were detected in 28.9% and noroviruses in 9.7% of the specimens, with G1
      rotaviruses and GII noroviruses accounting for the majority of each respective
      virus. Various strains in this study predated the currently assigned dates of
      discovery for their particular genotype, and in addition, two noroviruses (KL45
      and T091) could not be assigned to current genotypes. Phylogenetic analyses
      demonstrated a relative constancy in circulating rotavirus genotypes over time,
      with several genotypes from this study becoming established in the current
      repertoire of viral species. Similarly, GII noroviruses have maintained
      dominance, with GII.4 noroviruses continuing as a predominant genotype over time.
      Taken together, the complex molecular epidemiology of rotaviruses and noroviruses
      circulating in the 1970's is consistent with current patterns, an important
      consideration in the design of multivalent vaccines to control these viruses.

PMID- 23536876
TI  - FoxM1 is associated with poor prognosis of non-small cell lung cancer patients
      through promoting tumor metastasis.
AB  - BACKGROUND: FoxM1 has been reported to be important in initiation and progression
      of various tumors. However, whether FoxM1 has any indication for prognosis in non
      small cell lung cancer patients remains unclear. METHODOLOGY/PRINCIPAL FINDINGS:
      In this study, FoxM1 expression in tumor cells was examined first by
      immunohistochemistry in 175 NSCLC specimens, the result of which showed that
      FoxM1 overexpression was significantly associated with positive smoking status (P
      = 0.001), poorer tissue differentiation (P = 0.0052), higher TNM stage
      (P<0.0001), lymph node metastasis (P<0.0001), advanced tumor stage (P<0.0001),
      and poorer prognosis (P<0.0001). Multivariable analysis showed that FoxM1
      expression increased the hazard of death (hazard ratio, 1.899; 95% CI, 1.016
      3.551). Furthermore, by various in vitro and in vivo experiments, we showed that
      targeted knockdown of FoxM1 expression could inhibit the migratory and invasive
      abilities of NSCLC cells, whereas enforced expression of FoxM1 could increased
      the invasion and migration of NSCLC cells. Finally, we found that one of the
      cellular mechanisms by which FoxM1 promotes tumor metastasis is through inducing
      epithelial-mesenchymal transition (EMT) program. CONCLUSIONS: These results
      suggested that FoxM1 overexpression in tumor tissues is significantly associated
      with the poor prognosis of NSCLC patients through promoting tumor metastasis.

PMID- 23536877
TI  - Macrophages as IL-25/IL-33-responsive cells play an important role in the
      induction of type 2 immunity.
AB  - Type 2 immunity is essential for host protection against nematode infection but
      is detrimental in allergic inflammation or asthma. There is a major research
      focus on the effector molecules and specific cell types involved in the
      initiation of type 2 immunity. Recent work has implicated an important role of
      epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that
      are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The
      identities of the cell types that mediate the effects of IL-25/IL-33, however,
      remain to be fully elucidated. In the present study, we demonstrate that
      macrophages as IL-25/IL-33-responsive cells play an important role in inducing
      type 2 immunity using both in vitro and in vivo approaches. Macrophages produced
      type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in
      vitro, or were the IL-13-producing cells in mice administrated with exogenous IL
      33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced
      alternative activation of macrophages primarily through autocrine IL-13
      activating the IL-4Ralpha-STAT6 pathway. Moreover, depletion of macrophages
      attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive
      transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides
      bakeri infection induced worm expulsion accompanied by a potent type 2 protective
      immune response. Thus, macrophages represent a unique population of the innate
      immune cells pivotal to type 2 immunity and a potential therapeutic target in
      controlling type 2 immunity-mediated inflammatory pathologies.

PMID- 23536878
TI  - Potentiation of scutellarin on human tongue carcinoma xenograft by low-intensity
      ultrasound.
AB  - Scutellarin 7-O-beta-d-glucuronide (scutellarin) has shown great potential as a
      chemotherapeutic agent for cancer treatment, but only at high dosage. Here we
      investigate the possibility of using low intensity ultrasound to reduce the
      scutellarin dosage. Ultrasound intensities of 1.0 W/cm(2) and 0.05 W/cm(2) were
      used for in vivo and in vitro experiments, respectively, and a very low dosage of
      scutellarin (15 nM) was used. Tumor-bearing Balb/c mice and SAS human-tongue
      squamous carcinoma cell suspensions were used for the in vivo and in vitro
      experiments, respectively. Each kind of subjects was divided into control,
      ultrasound-alone, scutellarin-alone, and combined ultrasound-scutellarin
      treatment groups. Only the combined treatment showed strong anticancer effects.
      In the in vivo case, the combined treatment significantly delayed tumor growth,
      initiated cellular chromatin changes (including a decrease in the number of
      cytoplasmic organelles and fragmentation of condensed nuclear chromatin),
      inhibited tumor angiogenesis and lymphangiogenesis, stopped cancer-cell
      proliferation, decreased MMP-2 and MMP-9 expression levels and caused cancer-cell
      apoptosis. In the in vitro case, the combined treatment produced cancer cell
      shape irregularity in a manner seriously fractured microvilli, inhibited cancer
      cell migratory and invasion activities, and induced cancer-cell apoptosis.
      Because the combined treatment did not increase intracellular ROS production,
      scutellarin is not a sonosensitizer so that the anticancer effect is not through
      sonodynamic therapy. Low-intensity ultrasound is merely increasing the
      permeability of scutellarin into cancer cells. Based on our results, one may
      perform localized chemotherapy using much reduced dosage of the drug with the
      help of low intensity ultrasound, which will greatly minimize side effects.

PMID- 23536879
TI  - Exploration of noncoding sequences in metagenomes.
AB  - Environment-dependent genomic features have been defined for different
      metagenomes, whose genes and their associated processes are related to specific
      environments. Identification of ORFs and their functional categories are the most
      common methods for association between functional and environmental features.
      However, this analysis based on finding ORFs misses noncoding sequences and,
      therefore, some metagenome regulatory or structural information could be
      discarded. In this work we analyzed 23 whole metagenomes, including coding and
      noncoding sequences using the following sequence patterns: (G+C) content, Codon
      Usage (Cd), Trinucleotide Usage (Tn), and functional assignments for ORF
      prediction. Herein, we present evidence of a high proportion of noncoding
      sequences discarded in common similarity-based methods in metagenomics, and the
      kind of relevant information present in those. We found a high density of
      trinucleotide repeat sequences (TRS) in noncoding sequences, with a regulatory
      and adaptive function for metagenome communities. We present associations between
      trinucleotide values and gene function, where metagenome clustering correlate
      with microorganism adaptations and kinds of metagenomes. We propose here that
      noncoding sequences have relevant information to describe metagenomes that could
      be considered in a whole metagenome analysis in order to improve their
      organization, classification protocols, and their relation with the environment.

PMID- 23536880
TI  - Identification and Characterisation CRN Effectors in Phytophthora capsici Shows
      Modularity and Functional Diversity.
AB  - Phytophthora species secrete a large array of effectors during infection of their
      host plants. The Crinkler (CRN) gene family encodes a ubiquitous but understudied
      class of effectors with possible but as of yet unknown roles in infection. To
      appreciate CRN effector function in Phytophthora, we devised a simple Crn gene
      identification and annotation pipeline to improve effector prediction rates. We
      predicted 84 full-length CRN coding genes and assessed CRN effector domain
      diversity in sequenced Oomycete genomes. These analyses revealed evidence of CRN
      domain innovation in Phytophthora and expansion in the Peronosporales. We
      performed gene expression analyses to validate and define two classes of CRN
      effectors, each possibly contributing to infection at different stages. CRN
      localisation studies revealed that P. capsici CRN effector domains target the
      nucleus and accumulate in specific sub-nuclear compartments. Phenotypic analyses
      showed that few CRN domains induce necrosis when expressed in planta and that one
      cell death inducing effector, enhances P. capsici virulence on Nicotiana
      benthamiana. These results suggest that the CRN protein family form an important
      class of intracellular effectors that target the host nucleus during infection.
      These results combined with domain expansion in hemi-biotrophic and necrotrophic
      pathogens, suggests specific contributions to pathogen lifestyles. This work will
      bolster CRN identification efforts in other sequenced oomycete species and set
      the stage for future functional studies towards understanding CRN effector
      functions.

PMID- 23536881
TI  - Side-to-end Lymphaticovenular anastomosis through temporary lymphatic expansion.
AB  - OBJECTIVE: The number of bypasses is the most important factor in
      lymphaticovenular anastomosis (LVA) for lymphedema treatment. Side-to-end (S-E)
      LVA, which can bypass bidirectional lymph flows via one anastomosis, is
      considered to be the most efficient bypass, but creation of lateral window to a
      small lymphatic vessel is technically demanding. To overcome the difficulty, we
      introduced S-E anastomosis through temporary lymphatic expansion (SEATTLE)
      procedure in S-E LVA. METHODS: This was a retrospective observational study set
      in a teaching hospital. Forty eight lower extremity lymphedema (LEL) patients
      underwent LVA. S-E LVAs were performed with (SEATTLE group) or without (non
      SEATTLE group) temporary lymphatic expansion. S-E LVAs were evaluated to compare
      anastomosis result in SEATTLE and non-SEATTLE groups. RESULTS: S-E LVAs resulted
      in 44 anastomoses in SEATTLE group (n = 25) and 37 anastomoses in non-SEATTLE
      group (n = 23). LEL index reduction in SEATTLE group was significantly greater
      than that in non-SEATTLE group (16.5+/-14.5 vs. 10.9+/-11.8, P = 0.041). Success
      rate of S-E LVA in SEATTLE group was significantly higher than that in non
      SEATTLE group (95.5% vs 81.1%, P = 0.040). Thirty seven of 44 (84.1%) lymph
      vessels in SEATTLE group were successfully dilated by temporary lymphatic
      expansion maneuver. All of 9 failed S-E LVAs used a lymphatic vessel with
      diameter of 0.35 mm or smaller. CONCLUSIONS: The SEATTLE procedure facilitates S
      E LVA by a simple and easy maneuver. When the diameter of the lymphatic vessel is
      0.35 mm or smaller even after the temporary lymphatic expansion maneuver, S-E LVA
      is not recommended due to relatively high failure rate.

PMID- 23536883
TI  - Dentists' dietary perception and practice patterns in a dental practice-based
      research network.
AB  - BACKGROUND: Dental caries are largely preventable, and epidemiological evidence
      for a relationship between diet and oral health is abundant. To date, however,
      dentists' perceptions about the role of diet and dentists' practice patterns
      regarding diet counseling have not been clarified. OBJECTIVE: THE PURPOSES OF
      THIS STUDY WERE TO: (1) examine discordance between dentists' perception of the
      importance of diet in caries treatment planning and their actual provision of
      diet counseling to patients, and (2) identify dentists' characteristics
      associated with their provision of diet counseling. DESIGN: The study used a
      cross-sectional study design consisting of a questionnaire survey in Japan.
      PARTICIPANTS: The study queried dentists working in outpatient dental practices
      who were affiliated with the Dental Practice-Based Research Network Japan
      (JDPBRN), which aims to allow dentists to investigate research questions and
      share experiences and expertise (n = 282). MEASUREMENT: Dentists were asked about
      their perceptions on the importance of diet and their practice patterns regarding
      diet counseling, as well as patient, practice, and dentist background data.
      RESULTS: The majority of participants (n = 116, 63%) recognized that diet is
      "more important" to oral health. However, among participants who think diet is
      "more important" (n = 116), only 48% (n = 56) provide diet counseling to more
      than 20% of their patients. Multiple logistic regression analysis suggested that
      several variables were associated with providing diet counseling; dentist gender,
      practice busyness, percentage of patients interested in caries prevention, caries
      risk assessment, and percentage of patients who receive blood pressure screening.
      CONCLUSIONS: Some discordance exists between dentists' perception of the
      importance of diet in caries treatment planning and their actual practice pattern
      regarding diet counseling to patients. Reducing this discordance may require
      additional dentist education, including nutritional and systemic disease
      concepts; patient education to increase perception of the importance of caries
      prevention; or removing barriers to practices' implementation of counseling.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01680848.

PMID- 23536882
TI  - Transcriptome sequencing of gene expression in the brain of the HIV-1 transgenic
      rat.
AB  - The noninfectious HIV-1 transgenic (HIV-1Tg) rat was developed as a model of AIDs
      related pathology and immune dysfunction by manipulation of a noninfectious HIV
      1(gag-pol) virus with a deleted 3-kb SphI-MscI fragment containing the 3' -region
      of gag and the 5' region of pol into F344 rats. Our previous studies revealed
      significant behavioral differences between HIV-1Tg and F344 control rats in their
      performance in the Morris water maze and responses to psychostimulants. However,
      the molecular mechanisms underlying these behavioral differences remain largely
      unknown. The primary goal of this study was to identify differentially expressed
      genes and enriched pathways affected by the gag-pol-deleted HIV-1 genome. Using
      RNA deep sequencing, we sequenced RNA transcripts in the prefrontal cortex,
      hippocampus, and striatum of HIV-1Tg and F344 rats. A total of 72 RNA samples
      were analyzed (i.e., 12 animals per group * 2 strains * 3 brain regions).
      Following deep-sequencing analysis of 50-bp paired-end reads of RNA-Seq, we used
      Bowtie/Tophat/Cufflinks suites to align these reads into transcripts based on the
      Rn4 rat reference genome and to measure the relative abundance of each
      transcript. Statistical analyses on each brain region in the two strains revealed
      that immune response- and neurotransmission-related pathways were altered in the
      HIV-1Tg rats, with brain region differences. Other neuronal survival-related
      pathways, including those encoding myelin proteins, growth factors, and
      translation regulators, were altered in the HIV-1Tg rats in a brain region
      dependent manner. This study is the first deep-sequencing analysis of RNA
      transcripts associated the HIV-1Tg rat. Considering the functions of the pathways
      and brain regions examined in this study, our findings of abnormal gene
      expression patterns in HIV-1Tg rats suggest mechanisms underlying the deficits in
      learning and memory and vulnerability to drug addiction and other psychiatric
      disorders observed in HIV-positive patients.

PMID- 23536884
TI  - Molecular regulation of Trypanosoma congolense-induced nitric oxide production in
      macrophages.
AB  - BALB/c mice are highly susceptible while C57BL/6 mice are relatively resistant to
      experimental Trypanosoma congolense infection. Several reports show that an early
      interferon-gamma (IFN-gamma) response in infected mice is critically important
      for resistance via the activation of macrophages and production of nitric oxide
      (NO). NO is a pivotal effector molecule and possesses both cytostatic and
      cytolytic properties for the parasite. However, the molecular mechanisms leading
      to T. congolense (TC)-induced NO release from macrophages are not known. In this
      study, we investigated the signaling pathways induced by trypanosomes in
      immortalized macrophage cell lines from the highly susceptible BALB/c (BALB.BM)
      and relatively resistant C57Bl/6 (ANA-1) mice. We found that T. congolense whole
      cell extract (TC-WCE) induces significantly higher levels of NO production in IFN
      gamma-primed ANA-1 than BALB.BM cells, which was further confirmed in primary
      bone marrow-derived macrophage (BMDM) cultures. NO production was dependent on
      mitogen-activated protein kinase (MAPK, including p38, Erk1/2, and JNK)
      phosphorylation and was significantly inhibited by specific MAPK inhibitors in
      BALB.BM, but not in ANA-1 cells. In addition, T. congolense- and IFN-gamma
      induced NO production in ANA-1 and BALB.BM cells was dependent on STAT1
      phosphorylation and was totally suppressed by the use of fludarabine (a specific
      STAT1 inhibitor). We further show that T. congolense induces differential iNOS
      transcriptional promoter activation in IFN-gamma-primed cells, which is dependent
      on the activation of both GAS1 and GAS2 transcription factors in BALB.BM but only
      on GAS1 in ANA-1 cells. Taken together, our findings show the existence of
      differential signalling events that lead to NO production in macrophages from the
      highly susceptible and relatively resistant mice following treatment with IFN
      gamma and T. congolense. Understanding these pathways may help identify
      immunomodulatory mechanisms that regulate the outcome of infection during
      Trypanosome infections.

PMID- 23536885
TI  - Expression of calcineurin activity after lung transplantation: a 2-year follow
      up.
AB  - The objective of this pharmacodynamic study was to longitudinally assess the
      activity of calcineurin during the first 2 years after lung transplantation. From
      March 2004 to October 2008, 107 patients were prospectively enrolled and their
      follow-up was performed until 2009. Calcineurin activity was measured in
      peripheral blood mononuclear cells. We report that calcineurin activity was
      linked to both acute and chronic rejection. An optimal activity for calcineurin
      with two thresholds was defined, and we found that the risk of rejection was
      higher when the enzyme activity was above the upper threshold of 102 pmol/mg/min
      or below the lower threshold of 12 pmol/mg/min. In addition, we report that the
      occurrence of malignancies and viral infections was significantly higher in
      patients displaying very low levels of calcineurin activity. Taken together,
      these findings suggest that the measurement of calcineurin activity may provide
      useful information for the management of the prevention therapy of patients
      receiving lung transplantation.

PMID- 23536886
TI  - Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.
AB  - Exonic deletions in NRXN1 have been associated with several neurodevelopmental
      disorders, including autism, schizophrenia and developmental delay. However, the
      molecular mechanism by which NRXN1 deletions impact neurodevelopment remains
      unclear. Here we used human induced pluripotent stem cells (hiPSCs) and human
      embryonic stem cells (hESCs) as models to investigate the functional impacts of
      NRXN1 knockdown. We first generated hiPSCs from skin fibroblasts and
      differentiated them into neural stem cells (NSCs). We reduced NRXN1 expression in
      NSCs via a controlled shRNAmir-based knockdown system during differentiation, and
      monitored the transcriptome alteration by RNA-Seq and quantitative PCR at several
      time points. Interestingly, half reduction of NRXN1 expression resulted in
      changes of expression levels for the cell adhesion pathway (20 genes, P = 2.8*10(
      6)) and neuron differentiation pathway (13 genes, P = 2.1*10(-4)), implicating
      that single-gene perturbation can impact biological networks important for
      neurodevelopment. Furthermore, astrocyte marker GFAP was significantly reduced in
      a time dependent manner that correlated with NRXN1 reduction. This observation
      was reproduced in both hiPSCs and hESCs. In summary, based on in vitro models,
      NRXN1 deletions impact several biological processes during neurodevelopment,
      including synaptic adhesion and neuron differentiation. Our study highlights the
      utility of stem cell models in understanding the functional roles of copy number
      variations (CNVs) in conferring susceptibility to neurodevelopmental diseases.

PMID- 23536887
TI  - Suppression of core 1 Gal-transferase is associated with reduction of TF and
      reciprocal increase of Tn, sialyl-Tn and Core 3 glycans in human colon cancer
      cells.
AB  - It has long been presumed, though with surprisingly little evidence, a
      competition between Core 1 Gal-transferase (C1GalT), Core 3 GlcNAc-transferase
      (C3GnT) and sialyl-transferase (ST6GalNAc-T) for elongation of O-linked mucin
      type glycans initiated with GalNAcalpha-Ser/Thr. This study tested this
      presumption by selective suppression of one of these glycosyltransferases and
      then analysed the expressions of the enzymatic products of the other three
      glycosyltransferases. It was found that siRNA suppression of C1GalT markedly
      reduced the expression of Galbeta1,3GalNAcalpha- (Core 1) and in the meantime
      increased the expressions of sialyl-GalNAcalpha- (sialyl-Tn), GalNAcalpha- (Tn)
      and GlcNAcbeta1,3GalNAcalpha- (Core 3)-associated glycans in human colon cancer
      HT29 and SW620 cells. This supports a competitive modification of the GalNAcalpha
      Ser/Thr between C1GalT, C3GnT and ST6GalNAc-T in O-glycan biosynthesis. As Tn, TF
      and sialyl-Tn are oncofetal antigens and are over-expressed in most human
      cancers, this information is useful for the development of glycosyltransferase
      targeted therapeutic strategies for cancer treatment.

PMID- 23536888
TI  - Association of dyslipidemia with renal cell carcinoma: a 1?2 matched case-control
      study.
AB  - Abnormal serum lipid profiles are associated with the risk of some cancers, but
      the direction and magnitude of the association with renal cell carcinoma is
      unclear. We explore the relationship between serum lipids and renal cell
      carcinoma via a matched case-control study. A 1?2-matched case-control study
      design was applied, where one renal cell carcinoma patient was matched to two non
      renal-cell-carcinoma residents with respect to age (+/-0 year) and gender. Cases
      (n = 248) were inpatients with a primary diagnosis of renal cell carcinoma,
      confirmed by pathology after operations. Controls were sampled from a community
      survey database matched on age and gender with cases, 2 controls for each case.
      Stratified Cox proportional hazard regression analysis was used to obtain hazard
      ratios and corresponding 95% confidence intervals of lipids level and
      dyslipidemia for the risk of renal cell carcinoma. Elevated serum cholesterol
      (p<0.001), LDL cholesterol (p<0.001), and HDL cholesterol (p = 0.003) are
      associated with decreased hazard of renal cell carcinoma, adjusting for obesity,
      smoke, hypertension and diabetes. However, risk caused by hTG showed no
      statistical significance (p = 0.263). This study indicates that abnormal lipid
      profile influences the risk of renal cell carcinoma.

PMID- 23536889
TI  - Ras-association domain of sorting Nexin 27 is critical for regulating expression
      of GIRK potassium channels.
AB  - G protein-gated inwardly rectifying potassium (GIRK) channels play an important
      role in regulating neuronal excitability. Sorting nexin 27b (SNX27b), which
      reduces surface expression of GIRK channels through a PDZ domain interaction,
      contains a putative Ras-association (RA) domain with unknown function. Deleting
      the RA domain in SNX27b (SNX27b-DeltaRA) prevents the down-regulation of
      GIRK2c/GIRK3 channels. Similarly, a point mutation (K305A) in the RA domain
      disrupts regulation of GIRK2c/GIRK3 channels and reduces H-Ras binding in vitro.
      Finally, the dominant-negative H-Ras (S17N) occludes the SNX27b-dependent
      decrease in surface expression of GIRK2c/GIRK3 channels. Thus, the presence of a
      functional RA domain and the interaction with Ras-like G proteins comprise a
      novel mechanism for modulating SNX27b control of GIRK channel surface expression
      and cellular excitability.

PMID- 23536890
TI  - Repeatable construction method for engineered zinc finger nuclease based on
      overlap extension PCR and TA-cloning.
AB  - Zinc finger nuclease (ZFN) is a useful tool for endogenous site-directed genome
      modification. The development of an easier, less expensive and repeatedly usable
      construction method for various sequences of ZFNs should contribute to the
      further widespread use of this technology. Here, we establish a novel
      construction method for ZFNs. Zinc finger (ZF) fragments were synthesized by PCR
      using short primers coding DNA recognition helices of the ZF domain. DNA-binding
      domains composed of 4 to 6 ZFs were synthesized by overlap extension PCR of these
      PCR products, and the DNA-binding domains were joined with a nuclease vector by
      TA cloning. The short primers coding unique DNA recognition helices can be used
      repeatedly for other ZFN constructions. By using this novel OLTA (OverLap
      extension PCR and TA-cloning) method, arbitrary ZFN vectors were synthesized
      within 3 days, from the designing to the sequencing of the vector. Four different
      ZFN sets synthesized by OLTA showed nuclease activities at endogenous target
      loci. Genetically modified mice were successfully generated using ZFN vectors
      constructed by OLTA. This method, which enables the construction of intended ZFNs
      repeatedly and inexpensively in a short period of time, should contribute to the
      advancement of ZFN technology.

PMID- 23536891
TI  - Ionizing radiation potentiates dihydroartemisinin-induced apoptosis of A549 cells
      via a caspase-8-dependent pathway.
AB  - This report is designed to explore the molecular mechanism by which
      dihydroartemisinin (DHA) and ionizing radiation (IR) induce apoptosis in human
      lung adenocarcinoma A549 cells. DHA treatment induced a concentration- and time
      dependent reactive oxygen species (ROS)-mediated cell death with typical
      apoptotic characteristics such as breakdown of mitochondrial membrane potential
      (Deltapsim), caspases activation, DNA fragmentation and phosphatidylserine (PS)
      externalization. Inhibition of caspase-8 or -9 significantly blocked DHA-induced
      decrease of cell viability and activation of caspase-3, suggesting the dominant
      roles of caspase-8 and -9 in DHA-induced apoptosis. Silencing of proapoptotic
      protein Bax but not Bak significantly inhibited DHA-induced apoptosis in which
      Bax but not Bak was activated. In contrast to DHA treatment, low-dose (2 or 4 Gy)
      IR induced a long-playing generation of ROS. Interestingly, IR treatment for 24 h
      induced G2/M cell cycle arrest that disappeared at 36 h after treatment. More
      importantly, IR synergistically potentiated DHA-induced generation of ROS,
      activation of caspase-8 and -3, irreparable G2/M arrest and apoptosis, but did
      not enhance DHA-induced loss of Deltapsim and activation of caspase-9. Taken
      together, our results strongly demonstrate the remarkable synergistic efficacy of
      combination treatment with DHA and low-dose IR for A549 cells in which IR
      potentiates DHA-induced apoptosis largely by enhancing the caspase-8-mediated
      extrinsic pathway.

PMID- 23536892
TI  - Surfactant protein-A modulates LPS-induced TLR4 localization and signaling via
      beta-arrestin 2.
AB  - The soluble C-type lectin surfactant protein (SP)-A mediates lung immune
      responses partially via its direct effects on alveolar macrophages (AM), the main
      resident leukocytes exposed to antigens. SP-A modulates the AM threshold of
      lipopolysaccharide (LPS) activity towards an anti-inflammatory phenotype both in
      vitro and in vivo through various mechanisms. LPS responses are tightly regulated
      via distinct pathways including subcellular TLR4 localization and thus ligand
      sensing. The cytosolic scaffold and signaling protein beta-arrestin 2 acts as
      negative regulator of LPS-induced TLR4 activation. Here we show that SP-A neither
      increases TLR4 abundancy nor co-localizes with TLR4 in primary AM. SP-A
      significantly reduces the LPS-induced co-localization of TLR4 with the early
      endosome antigen (EEA) 1 by promoting the co-localization of TLR4 with the post
      Golgi compartment marker Vti1b in freshly isolated AM from rats and wild-type
      (WT) mice, but not in beta-arrestin 2(-/-) AM. Compared to WT mice pulmonary LPS
      induced TNF-alpha release in beta-arrestin 2(-/-) mice is accelerated and
      enhanced and exogenous SP-A fails to inhibit both lung LPS-induced TNF-alpha
      release and TLR4/EEA1 positioning. SP-A, but not LPS, enhances beta-arrestin 2
      protein expression in a time-dependent manner in primary rat AM. The constitutive
      expression of beta-arrestin 2 in AM from SP-A(-/-) mice is significantly reduced
      compared to SP-A(+/+) mice and is rescued by SP-A. Prolonged endosome retention
      of LPS-induced TLR4 in AM from SP-A(-/-) mice is restored by exogenous SP-A, and
      is antagonized by beta-arrestin 2 blocking peptides. LPS induces beta-arrestin
      2/TLR4 association in primary AM which is further enhanced by SP-A. The data
      demonstrate that SP-A modulates LPS-induced TLR4 trafficking and signaling in
      vitro and in vivo engaging beta-arrestin 2.

PMID- 23536893
TI  - Interplay between DMD point mutations and splicing signals in Dystrophinopathy
      phenotypes.
AB  - DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy
      while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are
      found in 10% of cases and the production of alternatively spliced transcripts is
      considered a key modifier of disease severity. Several exonic mutations have been
      shown to induce exon-skipping, while splice site mutations result in exon
      skipping or activation of cryptic splice sites. However, factors determining the
      splicing pathway are still unclear. Point mutations provide valuable information
      regarding the regulation of pre-mRNA splicing and elements defining exon identity
      in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations
      related to clinical phenotype and their effect on muscle mRNA and dystrophin
      expression. Aberrant splicing was found in 27 mutations due to alteration of
      splice sites or splicing regulatory elements. Bioinformatics analysis was
      performed to test the ability of the available algorithms to predict consequences
      on mRNA and to investigate the major factors that determine the splicing pathway
      in mutations affecting splicing signals. Our findings suggest that the splicing
      pathway is highly dependent on the interplay between splice site strength and
      density of regulatory elements.

PMID- 23536894
TI  - A comprehensive molecular phylogeny of dalytyphloplanida (platyhelminthes:
      rhabdocoela) reveals multiple escapes from the marine environment and origins of
      symbiotic relationships.
AB  - In this study we elaborate the phylogeny of Dalytyphloplanida based on complete
      18S rDNA (156 sequences) and partial 28S rDNA (125 sequences), using a Maximum
      Likelihood and a Bayesian Inference approach, in order to investigate the origin
      of a limnic or limnoterrestrial and of a symbiotic lifestyle in this large group
      of rhabditophoran flatworms. The results of our phylogenetic analyses and
      ancestral state reconstructions indicate that dalytyphloplanids have their origin
      in the marine environment and that there was one highly successful invasion of
      the freshwater environment, leading to a large radiation of limnic and
      limnoterrestrial dalytyphloplanids. This monophyletic freshwater clade,
      Limnotyphloplanida, comprises the taxa Dalyelliidae, Temnocephalida, and most
      Typhloplanidae. Temnocephalida can be considered ectosymbiotic Dalyelliidae as
      they are embedded within this group. Secondary returns to brackish water and
      marine environments occurred relatively frequently in several dalyeliid and
      typhloplanid taxa. Our phylogenies also show that, apart from the
      Limnotyphloplanida, there have been only few independent invasions of the limnic
      environment, and apparently these were not followed by spectacular speciation
      events. The distinct phylogenetic positions of the symbiotic taxa also suggest
      multiple origins of commensal and parasitic life strategies within
      Dalytyphloplanida. The previously established higher-level dalytyphloplanid
      clades are confirmed in our topologies, but many of the traditional families are
      not monophyletic. Alternative hypothesis testing constraining the monophyly of
      these families in the topologies and using the approximately unbiased test, also
      statistically rejects their monophyly.

PMID- 23536895
TI  - TGF-Beta suppresses VEGFA-mediated angiogenesis in colon cancer metastasis.
AB  - The FET cell line, derived from an early stage colon carcinoma, is non
      tumorigenic in athymic nude mice. Engineered FET cells that express TGF-alpha
      (FETalpha) display constitutively active EGFR/ErbB signaling. These cells readily
      formed xenograft tumors in athymic nude mice. Importantly, FETalpha cells
      retained their response to TGF-beta-mediated growth inhibition, and, like the
      parental FET cells, expression of a dominant negative TGF-beta type II receptor
      (DNRII) in FETalpha cells (FETalpha/DNRII) abrogated responsiveness to TGF-beta
      induced growth inhibition and apoptosis under stress conditions in vitro and
      increased metastatic potential in an orthotopic model in vivo, which indicates
      metastasis suppressor activity of TGF-beta signaling in this model. Cancer
      angiogenesis is widely regarded as a key attribute for tumor formation and
      progression. Here we show that TGF-beta signaling inhibits expression of vascular
      endothelial growth factor A (VEGFA) and that loss of autocrine TGF-beta in
      FETalpha/DNRII cells resulted in increased expression of VEGFA. Regulation of
      VEGFA expression by TGF-beta is not at the transcriptional level but at the post
      transcriptional level. Our results indicate that TGF-beta decreases VEGFA protein
      stability through ubiquitination and degradation in a PKA- and Smad3-dependent
      and Smad2-independent pathway. Immunohistochemical (IHC) analyses of orthotopic
      tumors showed significantly reduced TGF-beta signaling, increased CD31 and VEGFA
      staining in tumors of FETalpha/DNRII cells as compared to those of vector control
      cells. These results indicate that inhibition of TGF-beta signaling increases
      VEGFA expression and angiogenesis, which could potentially contribute to enhanced
      metastasis of those cells in vivo. IHC studies performed on human colon
      adenocarcinoma specimens showed that TGF-beta signaling is inversely correlated
      with VEGFA expression, indicating that TGF-beta-mediated suppression of VEGFA
      expression exists in colon cancer patients.

PMID- 23536896
TI  - Trophic interactions and distribution of some Squaliforme sharks, including new
      diet descriptions for Deania calcea and Squalus acanthias.
AB  - Squaliforme sharks are a common but relatively vulnerable bycatch in many deep
      water fisheries. Eleven species of squaliforme shark are commonly caught at
      depths of 200-1200 m on Chatham Rise, New Zealand, and their diversity suggests
      they might occupy different niches. The diets of 133 Deania calcea and 295
      Squalus acanthias were determined from examination of stomach contents. The diet
      of D. calcea was characterised by mesopelagic fishes, and S. acanthias by benthic
      to pelagic fishes, but was more adaptive and included likely scavenging.
      Multivariate analyses found the most important predictors of diet variability in
      S. acanthias were year, bottom temperature, longitude, and fish weight. The diet
      of the nine other commonly caught squaliforme sharks was reviewed, and the
      spatial and depth distribution of all species on Chatham Rise described from
      research bottom trawl survey catches. The eleven species had a variety of
      different diets, and depth and location preferences, consistent with niche
      separation to reduce interspecific competition. Four trophic groups were
      identified, characterised by: mesopelagic fishes and invertebrates
      (Centroselachus crepidater, D. calcea, and Etmopterus lucifer); mesopelagic and
      benthopelagic fishes and invertebrates (Centroscymnus owstoni, Etmopterus
      baxteri); demersal and benthic fishes (Centrophorus squamosus, Dalatias licha,
      Proscymnodon plunketi); and a generalist diet of fishes and invertebrates (S.
      acanthias). The trophic levels of the species in each of the four groups were
      estimated as 4.18-4.24, 4.20-4.23, 4.24-4.48, and 3.84 respectively. The diet of
      Oxynotus bruniensis and Squalus griffini are unknown. The different niches
      occupied by different species are likely to influence their vulnerability to
      bottom trawl fisheries. Some species may benefit from fisheries through an
      increased availability of scavenged prey.

PMID- 23536897
TI  - A new microarray substrate for ultra-sensitive genotyping of KRAS and BRAF gene
      variants in colorectal cancer.
AB  - Molecular diagnostics of human cancers may increase accuracy in prognosis,
      facilitate the selection of the optimal therapeutic regimen, improve patient
      outcome, reduce costs of treatment and favour development of personalized
      approaches to patient care. Moreover sensitivity and specificity are fundamental
      characteristics of any diagnostic method. We developed a highly sensitive
      microarray for the detection of common KRAS and BRAF oncogenic mutations. In
      colorectal cancer, KRAS and BRAF mutations have been shown to identify a cluster
      of patients that does not respond to anti-EGFR therapies; the identification of
      these mutations is therefore clinically extremely important. To verify the
      technical characteristics of the microarray system for the correct identification
      of the KRAS mutational status at the two hotspot codons 12 and 13 and of the
      BRAF(V600E) mutation in colorectal tumor, we selected 75 samples previously
      characterized by conventional and CO-amplification at Lower Denaturation
      temperature-PCR (COLD-PCR) followed by High Resolution Melting analysis and
      direct sequencing. Among these samples, 60 were collected during surgery and
      immediately steeped in RNAlater while the 15 remainders were formalin-fixed and
      paraffin-embedded (FFPE) tissues. The detection limit of the proposed method was
      different for the 7 KRAS mutations tested and for the V600E BRAF mutation. In
      particular, the microarray system has been able to detect a minimum of about
      0.01% of mutated alleles in a background of wild-type DNA. A blind validation
      displayed complete concordance of results. The excellent agreement of the results
      showed that the new microarray substrate is highly specific in assigning the
      correct genotype without any enrichment strategy.

PMID- 23536898
TI  - Activation energy of extracellular enzymes in soils from different biomes.
AB  - Enzyme dynamics are being incorporated into soil carbon cycling models and
      accurate representation of enzyme kinetics is an important step in predicting
      belowground nutrient dynamics. A scarce number of studies have measured
      activation energy (Ea) in soils and fewer studies have measured Ea in arctic and
      tropical soils, or in subsurface soils. We determined the Ea for four typical
      lignocellulose degrading enzymes in the A and B horizons of seven soils covering
      six different soil orders. We also elucidated which soil properties predicted any
      measurable differences in Ea. beta-glucosidase, cellobiohydrolase, phenol oxidase
      and peroxidase activities were measured at five temperatures, 4, 21, 30, 40, and
      60 degrees C. Ea was calculated using the Arrhenius equation. beta-glucosidase
      and cellobiohydrolase Ea values for both A and B horizons in this study were
      similar to previously reported values, however we could not make a direct
      comparison for B horizon soils because of the lack of data. There was no
      consistent relationship between hydrolase enzyme Ea and the environmental
      variables we measured. Phenol oxidase was the only enzyme that had a consistent
      positive relationship between Ea and pH in both horizons. The Ea in the arctic
      and subarctic zones for peroxidase was lower than the hydrolases and phenol
      oxidase values, indicating peroxidase may be a rate limited enzyme in
      environments under warming conditions. By including these six soil types we have
      increased the number of soil oxidative enzyme Ea values reported in the
      literature by 50%. This study is a step towards better quantifying enzyme
      kinetics in different climate zones.

PMID- 23536899
TI  - The categorisation of non-categorical colours: a novel paradigm in colour
      perception.
AB  - In this paper, we investigate a new paradigm for studying the development of the
      colour 'signal' by having observers discriminate and categorize the same set of
      controlled and calibrated cardinal coloured stimuli. Notably, in both tasks, each
      observer was free to decide whether two pairs of colors were the same or belonged
      to the same category. The use of the same stimulus set for both tasks provides,
      we argue, an incremental behavioural measure of colour processing from detection
      through discrimination to categorisation. The measured data spaces are different
      for the two tasks, and furthermore the categorisation data is unique to each
      observer. In addition, we develop a model which assumes that the principal
      difference between the tasks is the degree of similarity between the stimuli
      which has different constraints for the categorisation task compared to the
      discrimination task. This approach not only makes sense of the current (and
      associated) data but links the processes of discrimination and categorisation in
      a novel way and, by implication, expands upon the previous research linking
      categorisation to other tasks not limited to colour perception.

PMID- 23536900
TI  - Excisional wound healing is delayed in a murine model of chronic kidney disease.
AB  - BACKGROUND: Approximately 15% of the United States population suffers from
      chronic kidney disease (CKD), often demonstrating an associated impairment in
      wound healing. This study outlines the development of a surgical murine model of
      CKD in order to investigate the mechanisms underlying this impairment. METHODS:
      CKD was induced in mice by partial cauterization of one kidney cortex and
      contralateral nephrectomy, modifying a previously published technique. After a
      minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit
      assessment of wound healing parameters. Wounds were harvested on postoperative
      days (POD) 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative
      PCR (qPCR). RESULTS: CKD mice exhibited deranged blood chemistry and hematology
      profiles, including profound uremia and anemia. Significant decreases in re
      epithelialization and granulation tissue deposition rates were found in uremic
      mice wounds relative to controls. On immunofluorescent analysis, uremic mice
      demonstrated significant reductions in cellular proliferation (BrdU) and
      angiogenesis (CD31), with a concurrent increase in inflammation (CD45) as
      compared to controls. CKD mice also displayed differential expression of wound
      healing-related genes (VEGF, IL-1beta, eNOS, iNOS) on qPCR. CONCLUSIONS: These
      findings represent the first reported investigation of cutaneous healing in a CKD
      animal model. Ongoing studies of this significantly delayed wound healing
      phenotype include the establishment of renal failure model in diabetic strains to
      study the combined effects of CKD and diabetes.

PMID- 23536901
TI  - Fragmented perception: slower space-based but faster object-based attention in
      recent-onset psychosis with and without Schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with impairments of the perception of
      objects, but how this affects higher cognitive functions, whether this impairment
      is already present after recent onset of psychosis, and whether it is specific
      for schizophrenia related psychosis, is not clear. We therefore tested the
      hypothesis that because schizophrenia is associated with impaired object
      perception, schizophrenia patients should differ in shifting attention between
      objects compared to healthy controls. To test this hypothesis, a task was used
      that allowed us to separately observe space-based and object-based covert
      orienting of attention. To examine whether impairment of object-based visual
      attention is related to higher order cognitive functions, standard
      neuropsychological tests were also administered. METHOD: Patients with recent
      onset psychosis and normal controls performed the attention task, in which space-
      and object-based attention shifts were induced by cue-target sequences that
      required reorienting of attention within an object, or reorienting attention
      between objects. RESULTS: Patients with and without schizophrenia showed slower
      than normal spatial attention shifts, but the object-based component of attention
      shifts in patients was smaller than normal. Schizophrenia was specifically
      associated with slowed right-to-left attention shifts. Reorienting speed was
      significantly correlated with verbal memory scores in controls, and with visual
      attention scores in patients, but not with speed-of-processing scores in either
      group. CONCLUSIONS: deficits of object-perception and spatial attention shifting
      are not only associated with schizophrenia, but are common to all psychosis
      patients. Schizophrenia patients only differed by having abnormally slow right-to
      left visual field reorienting. Deficits of object-perception and spatial
      attention shifting are already present after recent onset of psychosis. Studies
      investigating visual spatial attention should take into account the separable
      effects of space-based and object-based shifting of attention. Impaired
      reorienting in patients was related to impaired visual attention, but not to
      deficits of processing speed and verbal memory.

PMID- 23536902
TI  - Native macrophyte density and richness affect the invasiveness of a tropical
      poaceae species.
AB  - The role of the native species richness and density in ecosystem invasibility is
      a matter of concern for both ecologists and managers. We tested the hypothesis
      that the invasiveness of Urochloa arrecta (non-native in the Neotropics) is
      negatively affected by the species richness and abundance of native aquatic
      macrophytes in freshwater ecosystems. We first created four levels of macrophyte
      richness in a greenhouse (richness experiment), and we then manipulated the
      densities of the same native species in a second experiment (density experiment).
      When the native macrophytes were adults, fragments of U. arrecta were added, and
      their growth was assessed. Our results from the richness experiment corroborated
      the hypothesis of a negative relationship between the native species richness and
      the growth of U. arrecta, as measured by sprout length and root biomass. However,
      the resistance to invasion was not attributed to the presence of a particular
      native species with a greater competitive ability. In the density experiment, U.
      arrecta growth decreased significantly with an increased density of all five of
      the native species. Density strongly affected the performance of the Poaceae in a
      negative manner, suggesting that patches that are densely colonized by native
      macrophytes and less subject to disturbances will be more resistant to invasion
      than those that are poorly colonized and more commonly subjected to disturbances.
      Our density experiment also showed that some species exhibit a higher competitive
      ability than others (sampling effect). Although native richness and abundance
      clearly limit the colonization and establishment of U. arrecta, these factors
      cannot completely prevent the invasion of aquatic ecosystems by this Poaceae
      species.

PMID- 23536903
TI  - Identifying and classifying trait linked polymorphisms in non-reference species
      by walking coloured de bruijn graphs.
AB  - Single Nucleotide Polymorphisms are invaluable markers for tracing the genetic
      basis of inheritable traits and the ability to create marker libraries quickly is
      vital for timely identification of target genes. Next-generation sequencing makes
      it possible to sample a genome rapidly, but polymorphism detection relies on
      having a reference genome to which reads can be aligned and variants detected. We
      present Bubbleparse, a method for detecting variants directly from next
      generation reads without a reference sequence. Bubbleparse uses the de Bruijn
      graph implementation in the Cortex framework as a basis and allows the user to
      identify bubbles in these graphs that represent polymorphisms, quickly, easily
      and sensitively. We show that the Bubbleparse algorithm is sensitive and can
      detect many polymorphisms quickly and that it performs well when compared with
      polymorphism detection methods based on alignment to a reference in Arabidopsis
      thaliana. We show that the heuristic can be used to maximise the number of true
      polymorphisms returned, and with a proof-of-principle experiment show that
      Bubbleparse is very effective on data from unsequenced wild relatives of potato
      and enabled us to identify disease resistance linked genes quickly and easily.

PMID- 23536904
TI  - Increasing trends of diabetes mellitus and body weight: a ten year observation at
      gondar university teaching referral hospital, northwest ethiopia.
AB  - BACKGROUND: Diabetes mellitus is becoming one of the major causes of premature
      adult mortality in developing countries. However, there is a very little
      documentation of the morbidity trend in such countries. OBJECTIVE: To assess the
      ten-year trend of diabetes mellitus at Gondar University Teaching Referral
      Hospital, northwest Ethiopia. METHODS: A hospital-based retrospective record
      review was done at the main referral hospital in northwest Ethiopia. Data were
      obtained from medical records of all registered diabetic patients in the Diabetic
      Follow up Clinic between 2000 and 2009. An Extended Mantel-Haenzel chi-square
      test for the linear trend was used to examine the trend over time. RESULT: Out of
      the total 354,524 patients who visited the Outpatient Department of the hospital
      during the study period, 1553 (4.4/1000) were diabetes patients, of which 50.1%
      was type 1 and 49.9% type 2 diabetes mellitus. The average increase in the
      proportion of both Type 1 and Type 2 diabetes mellitus cases between 2000 and
      2009 was 125%. The mean (+/-SD) age for Type 1 diabetes mellitus was 29.1 (+/
      12), and 53.5 (+/-12) for Type 2 diabetes. Overall 42.5% of the diabetes mellitus
      patients were female and 31.7% were rural residents. The mean body mass index for
      both type of diabetes mellitus increased from 15.9 to 18.3 kg for type 1 and from
      23.8 to 24.6 for type 2 between 2000 and 2009, respectively. CONCLUSION: The
      number of diabetes mellitus cases seen at Gondar Referral Hospital is rising
      steadily. A comprehensive diabetes prevention, treatment, and care program is
      needed to improve the quality of life of the increasing diabetes mellitus cases
      in Ethiopia.

PMID- 23536905
TI  - Protein kinase G1 alpha overexpression increases stem cell survival and cardiac
      function after myocardial infarction.
AB  - BACKGROUND: We hypothesized that overexpression of cGMP-dependent protein kinase
      type 1alpha (PKG1alpha) could mimic the effect of tadalafil on the survival of
      bone marrow derived mesenchymal stem cells (MSCs) contributing to regeneration of
      the ischemic heart. METHODS AND RESULTS: MSCs from male rats were transduced with
      adenoviral vector encoding for PKG1alpha ((PKG1alpha)MSCs).Controls included
      native MSCs ((Nat)MSCs) and MSCs transduced with an empty vector ((Null)MSCs).
      PKG1alpha activity was increased approximately 20, 5 and 16 fold respectively in
      (PKG1alpha)MSCs. (PKG1alpha)MSCs showed improved survival under oxygen and
      glucose deprivation (OGD) which was evidenced by lower LDH release, caspase-3/7
      activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt,
      pGSK3beta, and Bcl-2 were significantly increased in (PKG1alpha)MSCs compared to
      (Nat)MSCs and (Null)MSCs. Higher release of multiple prosurvival and angiogenic
      factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in (PKG1alpha)MSCs before
      and after OGD. In a female rat model of acute myocardial infarction,
      (PKG1alpha)MSCs group showed higher survival compared with (Null)MSCs group at 3
      and 7 days after transplantation as determined by TUNEL staining and sry-gene
      quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine
      factors in vitro were also identified. Immunostaining for cardiac troponin I
      combined with GFP showed increased myogenic differentiation of (PKG1alpha)MSCs.
      At 4 weeks after transplantation, compared to DMEM group and (Null)MSCs group,
      (PKG1alpha)MSCs group showed increased blood vessel density in infarct and peri
      infarct areas (62.5+/-7.7; 68.8+/-7.3 per microscopic view, p<0.05) and
      attenuated infarct size (27.2+/-2.5%, p<0.01). Heart function indices including
      ejection fraction (52.1+/-2.2%, p<0.01) and fractional shortening (24.8%+/-1.3%,
      p<0.01) were improved significantly in (PKG1alpha)MSCs group. CONCLUSION:
      Overexpression of PKG1alpha transgene could be a powerful approach to improve
      MSCs survival and their angiomyogenic potential in the infarcted heart.

PMID- 23536906
TI  - Tissue-specific transcriptomic profiling of Sorghum propinquum using a rice
      genome array.
AB  - Sorghum (Sorghum bicolor) is one of the world's most important cereal crops. S.
      propinquum is a perennial wild relative of S. bicolor with well-developed
      rhizomes. Functional genomics analysis of S. propinquum, especially with respect
      to molecular mechanisms related to rhizome growth and development, can contribute
      to the development of more sustainable grain, forage, and bioenergy cropping
      systems. In this study, we used a whole rice genome oligonucleotide microarray to
      obtain tissue-specific gene expression profiles of S. propinquum with special
      emphasis on rhizome development. A total of 548 tissue-enriched genes were
      detected, including 31 and 114 unique genes that were expressed predominantly in
      the rhizome tips (RT) and internodes (RI), respectively. Further GO analysis
      indicated that the functions of these tissue-enriched genes corresponded to their
      characteristic biological processes. A few distinct cis-elements, including ABA
      responsive RY repeat CATGCA, sugar-repressive TTATCC, and GA-responsive TAACAA,
      were found to be prevalent in RT-enriched genes, implying an important role in
      rhizome growth and development. Comprehensive comparative analysis of these
      rhizome-enriched genes and rhizome-specific genes previously identified in Oryza
      longistaminata and S. propinquum indicated that phytohormones, including ABA, GA,
      and SA, are key regulators of gene expression during rhizome development. Co
      localization of rhizome-enriched genes with rhizome-related QTLs in rice and
      sorghum generated functional candidates for future cloning of genes associated
      with rhizome growth and development.

PMID- 23536907
TI  - Activation of nuclear factor-kappaB in the brain after experimental subarachnoid
      hemorrhage and its potential role in delayed brain injury.
AB  - It has been reported that inflammation is involved in brain injury after
      subarachnoid hemorrhage (SAH). Nuclear factor-kappaB (NF-kappaB) is a key
      transcriptional regulator of inflammatory genes. Here, we used pyrrolidine
      dithiocarbamate(PDTC), an inhibitor of NF-kappaB, through intracisternal
      injection to study the role of NF-kappaB in delayed brain injury after SAH. A
      total of 55 rabbits were randomly divided into five groups: the control group;
      the SAH groups including Day-3, 5, and 7 SAH groups (the rabbits in these groups
      were sacrificed at 3, 5, 7 days after SAH, respectively); and the PDTC group (n =
      11 for each group). Electrophoretic mobility shift assay (EMSA) was performed to
      detect NF-kappaB DNA-binding activity. The mRNA levels of tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, and intercellular adhesion molecule (ICAM)-1
      were evaluated by RT-PCR analysis. Deoxyribonucleic acid fragmentation was
      detected by TUNEL and p65 immunoactivity was assessed by immunohistochemistry.
      Our results showed the activation of NF-kappaB after SAH, especially at day 3 and
      5. The activated p65 was detected in neurons. NF-kappaB DNA-binding activity was
      suppressed by intracisternal administration of PDTC. Increased levels of the TNF
      alpha, IL-1beta, and ICAM-1 mRNA were found in the brain at day 5 after SAH, and
      which were suppressed in the PDTC group. The number of TUNEL-positive cells also
      decreased significantly in the PDTC group compared with that in the Day-5 SAH
      group. These results demonstrated that the activated NF-kappaB in neurons after
      SAH plays an important role in regulating the expressions of inflammatory genes
      in the brain, and ultimately contributes to delayed brain injury.

PMID- 23536908
TI  - Antibody repertoire in paraneoplastic cerebellar degeneration and small cell lung
      cancer.
AB  - The goal of this study is to determine whether patients with paraneoplastic
      cerebellar degeneration (PCD) and small-cell lung cancer (SCLC) have a specific
      repertoire of antibodies, if SOX1 antibodies (SOX1-ab) can predict the presence
      of SCLC, and if antibodies to cell surface antigens occur in this syndrome.
      Antibody analysis was done using immunohistochemistry on rat brain, immunoblot
      with recombinant antigens, screening of cDNA expression libraries, and
      immunolabeling of live neurons in 39 patients with PCD and SCLC. VGCC-ab were
      measured by RIA, and SOX1-ab, Hu-ab, and ZIC4-ab by immunoblot. Lambert-Eaton
      myastenic syndrome (LEMS) was present in 10 of 23 patients with
      electrophysiological studies. At least one antibody was detected in 72% of
      patients. The individual frequencies were: 49% SOX1-ab, 44% VGCC-ab, 31% Hu-ab,
      and 13% ZIC4-ab. SOX1-ab occurred in 76% of patients with VGCC-ab and 27% of
      those without VGCC-ab (p = 0.0036). SOX1-ab were not found in 39 patients with
      sporadic late-onset cerebellar ataxia, 23 with cerebellar ataxia and glutamic
      acid decarboxylase antibodies, and 73 with PCD and cancer types other than SCLC
      (31 without onconeural antibodies, 25 with Yo-ab , 17 with Tr-ab). Five patients
      (13%) had antibodies against unknown neuronal cell surface antigens but none of
      them improved with immunotherapy. One serum immunoreacted against the axon
      initial segment of neurons and another serum against ELKS1, a protein highly
      expressed in the cerebellum that interacts with the beta4-subunit of the VGCC. In
      conclusion, 72% of patients with PCD and SCLC had one or more antibodies that
      indicate the presence of this tumor. In these patients, VGCC-ab and SOX1-ab occur
      tightly associated. SOX1-ab are predictors of SCLC in ataxia patients with a
      specificity of 100% and sensitivity of 49%. Unlike limbic encephalitis with SCLC,
      antibodies to cell surface antigens other than VGCC-ab, are infrequent and do not
      predict response to treatment.

PMID- 23536909
TI  - Assessing the consequences of denoising marker-based metagenomic data.
AB  - Early marker-based metagenomic studies were performed without properly accounting
      for the effects of noise (sequencing errors, PCR single-base errors, and PCR
      chimeras). Denoising algorithms have been developed, but they were validated
      using data derived from mock communities, in which the true sequences were known.
      Since the algorithms were designed to be used in real community studies, it is
      important to evaluate the results in such cases. With this goal in mind, we
      processed a real 16S rRNA metagenomic dataset through five denoising pipelines.
      By reconstituting the sequence reads at each stage of the pipelines, we
      determined how the reads were being altered. In one denoising pipeline,
      AmpliconNoise, we found that the algorithm that was designed to remove
      pyrosequencing errors changed the reads in a manner inconsistent with the known
      spectrum of these errors, until one of the parameters was increased substantially
      from its default value. Additionally, because the longest read was picked as the
      representative for each cluster, sequences were added to the 3' ends of shorter
      reads that were often dissimilar from what had been removed by the truncations of
      the previous filtering step. In QIIME, the denoising algorithm caused a much
      larger number of changes to the reads unless the parameters were changed from
      their defaults. The denoising pipeline in mothur avoided some of these negative
      side-effects because of its strict default filtering criteria, but these criteria
      also greatly limited the sequence information produced at the end of the
      pipeline. We recommend that those using these denoising pipelines be cognizant of
      these issues and examine how their reads are being transformed by the denoising
      process as a component of their analysis.

PMID- 23536910
TI  - Incidence and predictors of hospitalization for bacterial infection in community
      based patients with type 2 diabetes: the fremantle diabetes study.
AB  - BACKGROUND: The few studies that have examined the relationship between diabetes
      and bacterial infections have utilized administrative databases and/or have had
      limited/incomplete data including recognized infection risk factors. The aim of
      this study was to determine the incidence and associates of bacterial infection
      severe enough to require hospitalization in well-characterized community-based
      patients with type 2 diabetes. METHODS AND FINDINGS: We studied a cohort of 1,294
      patients (mean+/-SD age 64.1+/-11.3 years) from the longitudinal observational
      Fremantle Diabetes Study Phase I (FDS1) and 5,156 age-, gender- and zip-code
      matched non-diabetic controls. The main outcome measure was incident
      hospitalization for bacterial infection as principal diagnosis between 1993 and
      2010. We also examined differences in statin use in 52 FDS1 pairs hospitalized
      with pneumonia (cases) or a contemporaneous non-infection-related cause
      (controls). During 12.0+/-5.4 years of follow-up, 251 (19.4%) patients were
      hospitalized on 368 occasions for infection (23.7/1,000 patient-years). This was
      more than double the rate in matched controls (incident rate ratio (IRR) (95%
      CI), 2.13 (1.88-2.42), P<0.001). IRRs for pneumonia, cellulitis, and
      septicemia/bacteremia were 1.86 (1.55-2.21), 2.45 (1.92-3.12), and 2.08 (1.41
      3.04), respectively (P<0.001). Among the diabetic patients, older age, male sex,
      prior recent infection-related hospitalization, obesity, albuminuria, retinopathy
      and Aboriginal ethnicity were baseline variables independently associated with
      risk of first hospitalization with any infection (P<=0.005). After adjustment for
      these variables, baseline statin treatment was not significant (hazard ratio (95%
      CI), 0.70 (0.39-1.25), P = 0.22). Statin use at hospitalization for pneumonia
      among the case-control pairs was similar (23.1% vs. 13.5%, P = 0.27).
      CONCLUSIONS: The risk of severe infection is increased among type 2 diabetic
      patients and is not reduced by statin therapy. There are a number of other easily
      accessible sociodemographic and clinical variables that could be used to optimize
      infection-related education, prevention and management in type 2 diabetes.

PMID- 23536911
TI  - Contribution of intracellular calcium and pH in ischemic uncoupling of cardiac
      gap junction channels formed of connexins 43, 40, and 45: a critical function of
      C-terminal domain.
AB  - Ischemia is known to inhibit gap junction (GJ) mediated intercellular
      communication. However the detail mechanisms of this inhibition are largely
      unknown. In the present study, we determined the vulnerability of different
      cardiac GJ channels formed of connexins (Cxs) 43, 40, and 45 to simulated
      ischemia, by creating oxygen glucose deprived (OGD) condition. 5 minutes of OGD
      decreased the junctional conductance (Gj) of Cx43, Cx40 and Cx45 by 53+/-3%, 64+/
      1% and 85+/-2% respectively. Reduction of Gj was prevented completely by
      restricting the change of both intracellular calcium ([Ca(2+)]i) and pH (pHi)
      with potassium phosphate buffer. Clamping of either [Ca(2+)]i or pHi, through
      BAPTA (2 mM) or HEPES (80 mM) respectively, offered partial resistance to
      ischemic uncoupling. Anti-calmodulin antibody attenuated the uncoupling of Cx43
      and Cx45 significantly but not of Cx40. Furthermore, OGD could reduce only 26+/
      2% of Gj in C-terminus (CT) truncated Cx43 (Cx43-Delta257). Tethering CT of Cx43
      to the CT-truncated Cx40 (Cx40-Delta249), and Cx45 (Cx45-Delta272) helped to
      resist OGD mediated uncoupling. Moreover, CT domain played a significant role in
      determining the junction current density and plaque diameter. Our results
      suggest; OGD mediated uncoupling of GJ channels is primarily due to elevated
      [Ca(2+)]i and acidic pHi, though the latter contributes more. Among Cx43, Cx40
      and Cx45, Cx43 is the most resistant to OGD while Cx45 is the most sensitive one.
      CT of Cx43 has major necessary elements for OGD induced uncoupling and it can
      complement CT of Cx40 and Cx45.

PMID- 23536913
TI  - Quantitative and sensitive detection of GNAS mutations causing mccune-albright
      syndrome with next generation sequencing.
AB  - Somatic activating GNAS mutations cause McCune-Albright syndrome (MAS). Owing to
      low mutation abundance, mutant-specific enrichment procedures, such as the
      peptide nucleic acid (PNA) method, are required to detect mutations in peripheral
      blood. Next generation sequencing (NGS) can analyze millions of PCR amplicons
      independently, thus it is expected to detect low-abundance GNAS mutations
      quantitatively. In the present study, we aimed to develop an NGS-based method to
      detect low-abundance somatic GNAS mutations. PCR amplicons encompassing exons 8
      and 9 of GNAS, in which most activating mutations occur, were sequenced on the
      MiSeq instrument. As expected, our NGS-based method could sequence the GNAS locus
      with very high read depth (approximately 100,000) and low error rate. A serial
      dilution study with use of cloned mutant and wildtype DNA samples showed a linear
      correlation between dilution and measured mutation abundance, indicating the
      reliability of quantification of the mutation. Using the serially diluted
      samples, the detection limits of three mutation detection methods (the PNA
      method, NGS, and combinatory use of PNA and NGS [PNA-NGS]) were determined. The
      lowest detectable mutation abundance was 1% for the PNA method, 0.03% for NGS and
      0.01% for PNA-NGS. Finally, we analyzed 16 MAS patient-derived leukocytic DNA
      samples with the three methods, and compared the mutation detection rate of them.
      Mutation detection rate of the PNA method, NGS and PNA-NGS in 16 patient-derived
      peripheral blood samples were 56%, 63% and 75%, respectively. In conclusion, NGS
      can detect somatic activating GNAS mutations quantitatively and sensitively from
      peripheral blood samples. At present, the PNA-NGS method is likely the most
      sensitive method to detect low-abundance GNAS mutation.

PMID- 23536912
TI  - Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.
AB  - OBJECTIVES: Naked DNA vaccines can be manufactured simply and are stable at
      ambient temperature, but require improved delivery technologies to boost
      immunogenicity. Here we explore in vivo electroporation for multivalent codon
      optimized human papillomavirus (HPV) L1 and L2 DNA vaccination. METHODS: Balb/c
      mice were vaccinated three times at two week intervals with a fusion protein
      comprising L2 residues ~11-88 of 8 different HPV types (11-88*8) or its DNA
      expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV
      type, or as a mixture of several high-risk HPV types and administered utilizing
      electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3
      months after the last vaccination. Sera from immunized mice were tested for in
      vitro neutralization titer, and protective efficacy upon passive transfer to
      naive mice and vaginal HPV challenge. Heterotypic interactions between L1
      proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation
      using type-specific monoclonal antibodies. RESULTS: Electroporation with L2
      multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1
      or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with
      titers approaching those induced by Gardasil. Co-expression of L2 neither
      augmented L1-specific responses nor induced L2-specific antibodies. Delivery of
      HPV L1 DNA via in vivo electroporation produces a stronger antibody response
      compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced
      neutralizing antibody titers were observed for certain types when vaccinating
      with a mixture of L1 (or L1+L2) vectors of multiple HPV types, likely resulting
      from heterotypic L1 interactions observed in co-immunoprecipitation studies. High
      titers were restored by vaccinating with individual constructs at different
      sites, or partially recovered by co-expression of L2, such that durable
      protective antibody titers were achieved for each type. DISCUSSION: Multivalent
      vaccination via in vivo electroporation requires spatial separation of individual
      type L1 DNA vaccines.

PMID- 23536914
TI  - Characterization and functional analysis of the potato pollen-specific
      microtubule-associated protein SBgLR in tobacco.
AB  - Microtubule-associated proteins play a crucial role in the regulation of
      microtubule dynamics, and are very important for plant cell and organ
      development. SBgLR is a potato pollen-specific protein, with five imperfect V-V-E
      K-K-N/E-E repetitive motifs that are responsible for microtubule binding
      activity. In present study, SBgLR showed typical microtubule-associated protein
      characteristics; it bound tubulin and microtubules, and colocalized with
      microtubules in vitro. We also found that SBgLR could form oligomers, and that
      both the SBgLR monomers and oligomers bundle microtubules in vitro. Constitutive
      expression of SBgLR in tobacco caused curving and right-handed twisting root
      growth, abnormal directional cell expansion and cell layer arrangement, and
      pollen abortion. Immunofluorescence staining assays revealed that microtubule
      organization is altered in root epidermal cells in SBgLR-overexpressing lines.
      These suggest that SBgLR functions as a microtubule-associated protein in pollen
      development. Our results indicate that normal organization of MTs may be crucial
      for pollen development.

PMID- 23536916
TI  - RISKS AND PRICES: THE ROLE OF USER SANCTIONS IN MARIJUANA MARKETS.

PMID- 23536917
TI  - Three-dimensional optical coherence tomography of the optic nerve head with
      myelinated nerve fibers.

PMID- 23536915
TI  - Subjective size perception depends on central visual cortical magnification in
      human v1.
AB  - In the Ebbinghaus illusion, the context surrounding an object modulates its
      subjectively perceived size. Previous work implicates human primary visual cortex
      (V1) as the neural substrate mediating this contextual effect. Here we studied in
      healthy adult humans how two different types of context (large or small inducers)
      in this illusion affected size perception by comparing each to a reference
      stimulus without any context. We found that individual differences in the
      magnitudes of the illusion produced by either type of context were correlated
      with V1 area defined through retinotopic mapping using functional MRI. However,
      participants' objective ability to discriminate the size of objects presented in
      isolation was unrelated to illusion strength and did not correlate with V1 area.
      Control analyses showed no correlations between behavioral measures and the
      overall V1 area estimated probabilistically on the basis of neuroanatomy alone.
      Therefore, subjective size perception correlated with variability in central
      cortical magnification rather than the anatomical extent of primary visual
      cortex. We propose that such changes in subjective perception of size are
      mediated by mechanisms that scale with the extent to which an individual's V1
      selectively represents the central visual field.

PMID- 23536918
TI  - The Seattle Longitudinal Study of Adult Cognitive Development.

PMID- 23536919
TI  - A note from the Editor-in-Chief.

PMID- 23536920
TI  - Redox-Responsive, Core Cross-Linked Polyester Micelles.
AB  - Monomethoxy poly(ethylene glycol)-b-poly(Tyr(alkynyl)-OCA), a biodegradable
      amphiphilic block copolymer, was synthesized by means of ring-opening
      polymerization of 5-(4-(prop-2-yn-1-yloxy)benzyl)-1,3-dioxolane-2,4-dione
      (Tyr(alkynyl)-OCA) and used to prepare core cross-linked polyester micelles via
      click chemistry. Core cross-linking not only improved the structural stability of
      the micelles but also allowed controlled release of cargo molecules in response
      to the reducing reagent. This new class of core cross-linked micelles can
      potentially be used in controlled release and drug delivery applications.

PMID- 23536921
TI  - ICU Outcome Predictions using Physiologic Trends in the First Two Days.
AB  - AIMS: This study aims to accurately predict patient mortality in the ICU. Given
      all physiologic measurements in the first 48 hours of the ICU stay, the Bayesian
      model of the study predicts outcome with a posterior probability. METHODS: This
      study modeled the outcome as a binary random variable dependent on trends of
      daily physiologic measures of the patient, where trends were conditionally
      independent given the outcome. A two-day trend is a sequence of two discrete
      values, one for each day. Each value (low, medium, high or unmeasured) is a
      function of the arithmetic mean of that measure on the corresponding day.
      RESULTS: The prediction performance of the model was measured as the minimum of
      sensitivity and positive predictive values. The model yielded a score of 0.39
      along with a Hosmer-Lemeshow H statistic of 36, which measures calibration. The
      perfect scores would be 1.0 and 0, respectively. CONCLUSION: The prediction
      performance of the study was an improvement over the established ICU scoring
      metric SAPS-I, whose score was 0.32. Calibration of the model outputs was
      comparable to that of SAPS-I.

PMID- 23536922
TI  - Systemic mastocytosis.

PMID- 23536923
TI  - An artsy artifact.

PMID- 23536924
TI  - [Are antihistamines really useless in allergic asthma?].

PMID- 23536925
TI  - [Exercise therapy - effects and deficits].

PMID- 23536926
TI  - [Borreliosis].

PMID- 23536927
TI  - [Psoriasis-arthritis].

PMID- 23536928
TI  - Management for patients with tubular adenoma.

PMID- 23536929
TI  - Surveillance colonoscopy in patients with a serrated polyp.

PMID- 23536930
TI  - Are clips useful in the prevention of delayed bleeding after endoscopic mucosal
      resection?

PMID- 23536931
TI  - Is there a difference in adenoma recurrence by race-ethnicity?

PMID- 23536932
TI  - Looking inwards.

PMID- 23536933
TI  - Samuel Ward Casscells III, MD.

PMID- 23536934
TI  - Human dissection and the science and art of Leonardo da Vinci.

PMID- 23536935
TI  - Reply: endobronchial ultrasound-guided transbronchial needle aspiration versus
      cervical mediastinoscopy: case selection is needed to maintain clinical as well
      as cost benefits.

PMID- 23536936
TI  - Reply: lung cancer diagnosis and staging centers.

PMID- 23536937
TI  - ASCs jump on the surgical checklist bandwagon.

PMID- 23536938
TI  - [Results of implementation of a hypertension control program in Russia in 2002
      2012].

PMID- 23536939
TI  - [The prehospital diagnosis of unstable angina pectoris in case of a mid-urbanized
      town of West Siberia: results of a population-based study].
AB  - AIM: To assess the prehospital diagnosis of unstable angina pectoris (UAP) in the
      population of a mid-urbanized town in West Siberia. SUBJECTS AND METHODS: The
      study was conducted using the WHO epidemiological program "The acute myocardial
      infarction registry" that had been implemented in Tomsk since 1984. All the
      registered patients aged 20 to 70 years who had been diagnosed as having unstable
      (progressive) angina pectoris before admission to hospital and after its
      discharge were examined. RESULTS: A total of 2760 cases of suspected UAP were
      registered over the 2-year study period. 2139 (77.5%) patients were examined,
      which allows the findings to be considered to be significant. UAP was verified in
      1477 (69.1%) patients. During the follow-up period, 1175 (79.5%) of the examined
      patients sought medical advice for acute UAP, most did at an emergency care
      station and regional polyclinics. The detection rate of the disease was 82.4%
      during the primary examination. In accordance with the diagnosis made, 65.48% of
      the patients were sent to hospital, including 81.42% who were to the therapy
      hospitals operating around the clock. 406 subjects were non-hospitalized; of them
      313 (77.09%) refused hospitalization; in this connection, they were referred for
      a cardiology dispensary to receive outpatient treatment. CONCLUSION: The
      prehospital diagnosis of UAP was found to have a rather high level while only
      every five patients with verified UAP were admitted to a specialized hospital.

PMID- 23536940
TI  - [Impact of angiotensionogen and angiotensin II receptor type 1 gene polymorphisms
      on the development and course of chronic heart failure].
AB  - AIM: To study the impact of angiotensinogen (AGT) and angiotensin II receptor
      type 1 (AGTR1) gene polymorphisms on the development and course of chronic heart
      failure (CHF) in patients with coronary heart disease (CHD). SUBJECTS AND
      METHODS: Two hundred and twenty-six patients (149 men and 77 women; mean age 55.9
      +/- 5.8 years) with CHF were examined. Genotypes were identified by the
      restriction fragment length polymorphism analysis of polymerase chain reaction
      products. A control group comprised 136 subjects (63 men and 73 women; mean age
      53.6 +/- 4.8 years) without signs of cardiovascular diseases, as evidenced by the
      examination. RESULTS: The T allele of the M235T polymorphism in the AGT gene was
      found to be associated with the development and unfavorable course of CHF in
      patients with CHD. At the same time, carriage of the M allele of the M235T
      polymorphism in the AGT gene reflected the favorable course of this disease. That
      of the C allele and A/C genotype of the A1166C polymorphism in the AGTR1 gene was
      associated with the development of CHF and the A allele and A/A genotype
      manifested themselves as protective factors. According to the severity of CHF and
      the nature of its course, the distribution of frequencies of the genotypes and
      alleles of the A1166C polymorphism in the AGTR1 gene showed no significant
      differences between the patient groups. CONCLUSION: There were associations of
      the polymorphisms of the AGT gene (the M235T polymorphic marker) and the AGTR1
      gene (the A1166C polymorphic marker) with the development of CHF in patients with
      CHD.

PMID- 23536941
TI  - [Relationship of subclinical atherosclerosis indicators to exercise tolerance in
      patients with coronary heart disease].
AB  - AIM: To study the spread of a number of indicators of subclinical atherosclerosis
      in patients with coronary heart disease (CHD) and the pattern of their
      relationship to their functional state and muscle mass. SUBJECTS AND METHODS:
      Twenty patients with chronic forms of CHD were examined. Vascular wall stiffness
      was judged from pulse wave velocity (PWV) along elastic-type vessels, by
      calculating the carotid-femoral index (CFI). Endothelial function was estimated
      by endothelium-dependent vasodilation (EDV) in a reactive hyperemia test.
      Ultrasound scanning of the common carotid artery was used to estimate intima
      media thickness. All the patients underwent bicycle ergometry; their exercise
      tolerance (ET) was determined by the amount of consumed oxygen when the metabolic
      equivalent (MET) was calculated; the percentages of active cell mass (ACM%) and
      lean mass (LM%) of total body weight were determined; the levels of total
      cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides
      were estimated. A control group comprised 20 matched persons without CHD.
      RESULTS: A prognostically unfavorable increase of >12 m/sec in CFI was revealed
      in 20% of the patients with CHD and in 10% of the controls; endothelial vasomotor
      dysfunction (EDV < 10%) in 65 and 50%; a more than 0.9-mm increase in 55 and 15%,
      respectively. A low ET was stated in the majority of patients with abnormal
      vascular stiffness and endothelial vasomotor dysfunction. The CHD patients with a
      low ET were found to have significant correlations of CFI with ACM% and LM%, EDV
      and ACM% and LM%, CFI and EDV. The control patients with a low ET also showed
      correlations of EDV and ACM% and LM%. There was a correlation of ACM% and LM%
      with MET in both groups. CONCLUSION: EDV and PWV reflect a more decrease in
      physical activity and dysadapted functional status than in the degree of
      subclinical atherosclerosis.

PMID- 23536942
TI  - [Effect of bosentan on the clinical status and cellular immunity of patients with
      idiopathic pulmonary hypertension].
AB  - AIM: To study the effect of bosentan on the clinical status and cellular immunity
      of patients with idiopathic pulmonary hypertension (IPH). SUBJECTS AND METHODS:
      The study enrolled 35 patients with Functional Class (FC) II and IV IPH who had
      received conventional therapy for 3 months. All the patients took bosentan 125
      mg/day for 4 weeks. Then they were randomized to have bosentan 125 or 250 mg/day
      (Groups 1 and 2). FC was assessed and 6-minute walk test (6MWT), transthoracic
      echocardiography (EchoCG), and right heart catheterization (RHC) were performed
      at baseline and after 12 weeks. Peripheral blood lymphocytes were
      immunophenotyped and the functional activity of neutrophils was determined by
      their ability to absorb latex particles at baseline and following 3 and 12 weeks.
      RESULTS: After 12 weeks of treatment, both groups showed a statistically
      significant increase in the distance covered during the 6MWT. The Borg index and
      FC also decreased statistically significantly. EchoCG demonstrated a
      statistically significant reduction in systolic pulmonary artery pressure (SPAP)
      in Group 1; and in Group 2, SPAP was lower at baseline and remained substantially
      unchanged (it statistically significantly decreased as evidenced by RHC).
      Bosentan statistically significantly diminished pulmonary vascular resistance in
      both groups. No adverse reactions were noted. At baseline, the patients showed a
      statistically significant elevation in NKT-like lymphocytes up to 10.79 +/- 6.2%.
      The other indicators of peripheral blood lymphocyte phenotyping did not exceed
      the normal range. The count of NKT-like lymphocytes remained significantly above
      the normal levels throughout the follow-up in both groups and slightly dropped in
      Group 1 patients only after 12 weeks of treatment. In Group 2, the level of
      CD3+CD25+ lymphocytes rose as compared to the normal levels at 3 and 12 weeks of
      treatment. At 3 weeks of treatment, there was a statistically significant
      difference between the groups in phagocytic number. CONCLUSION: Bosentan
      treatment statistically significantly improves the clinical status of patients
      with IPH and it is characterized by good tolerability. Bosentan does not exceed
      the normal count of peripheral blood NKT-like lymphocytes, but it has a direct or
      indirect positive effect on the B-lymphocytic component of the immune system in
      patients with IPH.

PMID- 23536943
TI  - [Sclerodegenerative aortic valve lesions and hereditary connective tissue
      disorders].
AB  - AIM: To estimate the role of different dysplastic syndromes and phenotypes in the
      development of sclerodegenerative lesions and calcific stenosis of the aortic
      valve (AV). SUBJECTS AND METHODS: One hundred and fifty patients (82 men and 68
      women) aged 42 to 83 years were examined. A study group consisted of 89 patients
      (mean age 60.7 +/- 8.9 years) with clinical and echocardiographic signs of
      sclerodegenerative AV lesions (SDAVL). A control group included 61 patients (mean
      age 61.3 +/- 7.6 years) who had no clinical, physical, or echocardiographic signs
      of SDAVL. Twenty-five patients with critical calcific aortic stenosis (CAS)
      underwent histological examination of removed aortic semilunar valves after
      prosthetic AV replacement. RESULTS: Persons with a Marfanoid habitus (18%) and
      mitral valve prolapse (10.7%) are most common in older age groups. An association
      has been found between the bone signs of dysmorphogenesis and the development of
      SDAVL and CAS. CONCLUSION: Three or more signs of bone dysmorphogenesis and the
      Marfanoid habitus should be viewed as a predictor of SDAVL.

PMID- 23536944
TI  - [Electrocardiographic predictors of in-hospital outcomes of acute coronary
      syndrome].
AB  - AIM: To estimate the time course of changes in basic electrocardiographic (ECG)
      parameters in patients with acute coronary syndrome (ACS) as possible predictors
      of in-hospital outcomes. MATERIALS AND METHODS: The data of 277 patients with
      acute coronary syndrome (ACS) were used; QT-interval duration was studied by
      means of an EC12C-01 cardioanalyzer; ST-segment deviation (sigmaST), elevation
      (sigmaST-E), and depression (sigmaST-D) sums, and corrected QT-interval
      dispersion (DQTc) were calculated. RESULTS: There were highly significant
      differences of sigmaST in all the patients groups at admission and differences of
      DQTc in ACS patients with and without ST-segment elevation. The survival rates
      were significantly different depending on the value of ECG parameters, such as
      sigmaST, sigmaST-D, and DQTc. CONCLUSION: The cardioanalyzer can automatically
      improve the estimation of in-hospital ECG changes and to determine predictors of
      an ACS outcome.

PMID- 23536945
TI  - [Specific features of rehabilitation in patients with gluten-sensitivity celiac
      disease].
AB  - AIM: To elaborate recommendations for rehabilitation of patients with gluten
      sensitivity celiac disease (GCD) on the basis of a long-term follow-up. SUBJECTS
      AND METHODS: Eighty-seven patients with GCD were followed up for as long as 31
      years. Of those, 72.4% of the patients kept strictly to their gluten-free diet
      (GFD) throughout the follow-up; 9.2% did not follow the diet periodically; and
      18.4% did not at all. The sera from 71 patients were tested for IgA and IgG anti
      gliadin antibodies (AGAb) and anti-tissue transglutaminase antibodies (ATTGAb) at
      as long as 19-year follow-up. AGAb and ATTGAb were estimated by enzyme
      immunoassay (IMMCO Diagnostics). All the patients underwent endoscopic and
      histological examinations of the small bowel mucosa (SBM). RESULTS: To support
      the validity of keeping to the GFD, the time course of clinical, laboratory, and
      morphological changes were analyzed in 63 and 24 GFD followers and non-followers,
      respectively. The GFD non-followers were more frequently found to have diarrheic
      syndrome, symptoms of malabsorption syndrome, lower serum concentrations of
      hemoglobin, total protein, iron, and calcium; no SBM structural recovery was seen
      in any patient. When the GFD was long adhered to, there was also a reduction in
      detection rates and AGAb and ATTGAb concentrations. CONCLUSION: The adherence to
      the GFD was ascertained to contribute to fuller rehabilitation in the patients.
      However, even the patients who had strictly kept to their GFD showed periods of
      an exacerbation and incomplete SBM structural recovery. Therefore, the
      rehabilitation system for patients with GCD must involve diagnostic, therapeutic,
      and organizational measures that promote not only rapid clinical recovery, but
      also better quality of life in these patients.

PMID- 23536946
TI  - [The porphyrin metabolism in liver cirrhosis].
AB  - AIM: To comparatively study porphyrin metabolic disturbances in liver cirrhosis
      (LC) of varying etiology and to estimate the diagnostic and prognostic value of
      the detected disorders. SUBJECTS AND METHODS: Seventy-one patients were examined;
      among them 34, 15, and 22 patients were diagnosed as having alcoholic, viral, and
      alcoholic-and-viral LC, respectively. Its predictors and porphyrin fractions were
      determined in their urine and feces. RESULTS: Porphyrin metabolic disturbances
      were recorded in 62 (87.3%) patients and found in the majority of patients with
      viral (86.7%), alcoholic (94.1%), and mixed (77.3%) LC. The detected
      abnormalities corresponded to 4 variants of porphyrin dysmetabolism: elevation of
      porphyrin predictors, biochemical syndromes of symptomatic elevation of fecal
      porphyrins, secondary coproporphyrinuria, and latent chronic hepatic porphyria
      (LCHP). Some patients were found to have comorbidities, suggesting the stepwise
      development of porphyrin dysmetabolism. The disturbances were identified in
      patients with LC irrespective of the Child-Pugh class. The prognostically less
      favorable biochemical syndrome LCHP was recorded only in the presence of
      progressive hepatocellular failure in Child's class C decompensated LC. This
      trend should be considered to be prognostically unfavorable, preceding or
      occurring in the presence of decompensated LC that is more often a cause of death
      in this contingent of patients. CONCLUSION: Porphyrin metabolism should be
      regarded as a highly sensitive indicator. The differential assessment of the
      porphyrin excretory profile may be referred to as additional diagnostic and
      prognostic criteria indicating the Child-Pugh class.

PMID- 23536947
TI  - [The clinical efficacy of a succinate-containing infusion drug during
      pharmacotherapy for hepatic lesions of varying genesis: results of meta
      analysis].
AB  - AIM: To pool the published results of trials of the new infusion hepatoprotector
      remaxol for the integral quantification of the magnitude of its clinical
      efficacy. SUBJECTS AND METHODS: The authors made a systematized review of the
      published results of randomized clinical trials of the succinate-containing
      infusion hepatoprotector remaxol in diseases associated with hepatic lesions
      (chronic hepatitis B and C, severe ethanol intoxication in the presence of
      alcohol dependence, drug-induced liver lesion during treatment of tuberculosis,
      and metabolic syndrome). The pooled database included information on 935
      patients. The combined control group (n = 447) received traditional
      pharmacotherapy drugs (active placebo), the treatment group (n = 628)
      additionally took remaxol. RESULTS: Meta-analysis of the frequency
      characteristics of positive outcomes (the rate of disappearance of major clinical
      symptoms and complications) and the activity range for the enzymes characterizing
      hepatocyte cytolysis (alanine aminotransferase and aspartate aminotransferase)
      and cholestasis (alkaline phosphatase and gamma-glutamate transpeptidase) in the
      compared groups could provide an integral evaluation of the clinical efficacy of
      remaxol, which was 1.57 for enzymatic activity and 1.78 for the frequency
      characteristics of outcomes. The odds ratio of positive outcomes was 2.9 (range
      1.9 to 3.9) and the number of patients who needed to be treated with remaxol
      during the follow-up to prevent a poor outcome in one patient was 6 (range 4 to
      8). CONCLUSION: The succinic acid-based infusion hepatoprotector remaxol provides
      a statistically and clinically significant therapeutic effect in the drug
      correction of hepatic lesions of varying genesis.

PMID- 23536948
TI  - [The prevalence and clinical aspects of Barrett's esophagus in the population of
      Eastern Siberia].
AB  - AIM: To study the prevalence and clinical aspects of Barrett's esophagus (BE) in
      natives and newcomers in East Siberia. SUBJECTS AND METHODS: Clinical
      examinations and esophagogastroduodenoscopy were performed in 12975 Caucasoids
      and 1489 Khakases in Abakan (Khakasia), 1861 Caucasoids and 5829 Tuvinians in
      Kyzyl (Republic of Tuva), and 1177 Caucasoids in Dudinka (Taimyr). The diagnosis
      of BE was verified by morphological study. RESULTS: Among the Caucasoids, the
      total prevalence of BE was 1.6% (2.4% in men and 0.8% in women; odds ratio (OR)
      was 3.21 with 95% CI 2.40-4.29; p < 0.001); among the Mongoloids, that was 3.1%
      (4.5% in men and 2% in women; OR, 2.3 with 95% CI 1.75-3.04; p < 0.001).
      Heartburn and other typical symptoms was more prevalent in patients with BE. The
      risk factors of BE in all the examined populations were male sex, age over 40
      years, smoking more than 20 cigarettes a day for 10 years or more in men, and
      obesity. CONCLUSION: There were ethnic differences in the prevalence of BE, which
      were prevalent in East Siberia in the Mongoloids as compared to the Caucasoids.

PMID- 23536949
TI  - [The diagnosis and treatment of common diseases detected during medical
      examination of male oil-extracting industry workers].
AB  - AIM: To study the health status of male shift workers engaged in oil-extracting
      industry in the Tyumen Region through prophylactic medical examination, to
      elaborate measures for the diagnosis and treatment of the most common diseases of
      the viscera and urogenital system (UGS). SUBJECTS AND METHODS: In 2009, the exit
      team of the Unit of Preventive Examinations, Tyumen Regional Clinical Hospital,
      examined 1120 male shift workers of the oil-field facilities of the Tyumen
      Region. RESULTS: The health of the examined shift workers was generally better
      than the national and regional indices. At the same time a number of observations
      demonstrated that shift work had a negative impact on the function of the viscera
      and UGS in the men, as evidenced by this clinical examination revealing arterial
      hypertension in 20 men and chronic bacterial prostatitis in 91. All patients with
      the newly identified diseases were registered to be followed up. In the
      extrashift period, they were successfully treated at the Diagnostic Center of the
      Tyumen Regional Hospital according to the national standards. CONCLUSION: The
      prophylactic medical examination of shift oil-field workers is substantiated by
      not only the compuIsory specialized examination for the early diagnosis of
      evolving diseases, but also by the fact that during their visits to specialists
      the men can really increase their awareness of their current health and the
      methods of its promotion.

PMID- 23536950
TI  - [Clinical and laboratory evaluation of the efficiency of chronic hemodialysis
      treatment using acidosuccinate in patients with terminal renal failure].
AB  - AIM: To evaluate the efficiency of using a succinate-containing dialysis solution
      (SCDS) in terminal renal failure patients treated with chronic hemodialysis
      (CHD). SUBJECTS AND METHODS: Ninety patients from two hemodialysis units took
      part in the crossover study and were allocated to 2 groups. For 6 months, study
      group patients received CHD using SCDS and control group patients had CHD with a
      standard bicarbonate dialysis solution after 3-month washout period followed by
      decussation. The time course of changes in blood biochemical parameters, 24-hour
      ECG monitoring data, and quality of life indicators were estimated in the
      patients. RESULTS: After using acidosuccinate during hemodialysis, there was a
      significant reduction in the predialysis serum level of inorganic phosphate, a
      calcium phosphate product, gamma-glutamyl transpeptidase, urea, and aldosterone
      as compared to the control group. The blood concentration of total protein was
      also increased. After 6-month administration of acidosuccinate, the patients
      showed reductions in systolic blood pressure, heart rate, and the frequency and
      duration of ST-segment depression episodes. There were positive changes in the
      quality of life of patients according to the KDQOL-SF questionnaire. CONCLUSION:
      The use of SCDS in patients with CHD causes positive changes in a number of
      laboratory parameters and improves the physical and general status, and quality
      of life of patients.

PMID- 23536951
TI  - [Plasminogen activator inhibitor type 1 gene polymorphism and thromboses in
      patients with antiphospholipid syndrome].
AB  - AIM: To estimate the prevalence of plasminogen activator inhibitor type 1 (PAI-1)
      gene polymorphism in patients with antiphospholipid syndrome (APS) and its
      implication in vascular disorders. SUBJECTS AND METHODS: The investigation
      enrolled 138 patients: 103 with APS, including 47 with systemic lupus
      erythematosus (SLE) + APS and 56 with primary APS (PAPS), 15 with SLE without
      APS, 20 with idiopathic thrombosis (IT), a control group (30 apparently healthy
      individuals). Thrombosis at various sites was recorded in 91 (88%) of the 103
      patients with APS. The authors analyzed both the presence of thrombotic events in
      all the groups and the number of cases of thrombosis in each patient.
      Antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin
      antibodies, and anti-beta2-glycoprotein type 1 antibodies, were studied in all
      the patients. To diagnose a genotype in patients by the code encoding for PAI-1,
      DNA isolated from peripheral blood by standard methods was used and further
      investigated by real-time polymerase chain reaction. RESULTS: Out of 91 patients
      with APS and thrombosis, 27 (30%) had the 4G/4G genotype, which corresponded to
      homozygous mutation in the PAI-1 gene, 50 (55%) had the 4G/5G genotype
      (heterozygous mutation), and 14 (15%) had the 5G/5G (a normal genotype). The PAI
      1 4G/5G genotype was present in 22 (70%) of 31 patients with SLE + APS and lower
      limb deep vein thrombosis versus 17 (470%) of 36 patients with PAPS (odds ratio
      (OR) 2.73; 95% confidence interval (CI), 0.89 to 8.59; p = 0.08) and in 9 (90%)
      of 10 patients with SLE + APS and pulmonary artery thromboembolism versus 8 (40%)
      of 20 patients with PAPS (OR 13,5; 95% CI, 1.23 to 344.98; p = 0.02). The
      incidence of thrombosis per 100 person-years was higher in the PAI-1 4G/4G and
      4G/5G groups: 35.4 and 28.1 cases per 100 person-years, respectively. Thromboses
      were least often in the group of patients with the PAI-1 5G/5G genotype (18.6).
      CONCLUSION: The prevalence of the PAI-1 5G/5G genotype in patients with APS and
      thrombosis was significantly lower than in those with SLE without APS or
      thrombosis. The 4G/5G polymorphism in APS in the presence of SLE was associated
      with venous thromboembolisms whereas in PAPS there was no relationship between
      the PAI-1 genotype, a history of thrombosis, and its localization.

PMID- 23536952
TI  - [Heart failure in cardiorenal syndromes].
AB  - This review considers the classification of cardiorenal syndromes (CRS), the
      pathogenesis of heart failure, and a search for therapeutic targets for its
      treatment, biomarkers for heart and kidney failure, difficulties in therapy and
      reversion of the pathogenetic continuum of CRS, and promises for the use of some
      new technologies to treat this condition.

PMID- 23536953
TI  - [Multislice spiral computed tomography of coronary arteries: procedure
      development stages and clinical application].
AB  - The paper analyzes the data available in the literature on the possibility of
      using multislice spiral computed tomography in patients with acute coronary
      syndrome. The authors give the results of their study of the diagnostic value of
      64-slice computed tomography in patients with presumptive coronary heart disease
      (CHD) and its high risk according to the Framingham risk scale (Group 1) versus
      those with its already established diagnosis (Group 2). The sensitivity of 64
      slice computed tomography was 97.8 and 90.2 in Groups 1 and 2, respectively; its
      specificity was 98.6 and 78.2% in these groups.

PMID- 23536954
TI  - [Nonglycemic effects of dipeptidyl peptidase-4 inhibitors].
AB  - The review considers the major nonglycemic effects of dipeptidyl peptidase-4
      inhibitors commonly used in diabetological practice, by using as an example
      sitagliptin, the first and most investigated representative of this class.

PMID- 23536955
TI  - [Antihistamine drugs, quinuclidine derivatives, in allergic diseases. What is
      their benefit?].
AB  - The extensive rise in the prevalence of allergic diseases (AD), which among the
      planet's population is now 15 to 30% or more, occupies the great attention of
      different specialists' to the mechanisms for the development and control of the
      symptoms of allergy. In view of the most important role of histamine in the
      pathogenesis of allergic diseases, antihistamines are first-line line drugs in
      the pharmacotherapy of AD. Quinuclidine derivatives that combine the most useful
      properties of the first and second generations occupy a special place among
      histamines. The paper gives the data of clinical trials of the efficacy of the
      antihistamines quinuclidine derivatives in the treatment of various allergic
      diseases.

PMID- 23536957
TI  - The role of MMP2 (-1306C>T) and TIMP2 (-418 G>C) promoter variants in age-related
      macular degeneration.
AB  - PURPOSE: To investigate the possible association between the matrix
      metalloproteinase 2 (-1306C>T) (rs 243865) and tissue inhibitors of matrix
      metalloproteinase 2 (-418 G>C) (rs 8179090) polymorphisms and the risk of age
      related macular degeneration. METHODS: This case-controlled prospective study
      included 144 age-related macular degeneration patients and 172 control subjects.
      All subjects were screened for age, gender, hypertension (HT), diabetes (DM), and
      body mass index (BMI). Serum levels of high-density lipoprotein cholesterol (HDL
      C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total
      cholesterol (TC), and smoking were also determined. Genomic DNA was extracted
      from peripheral leukocytes from ethylenediaminetetraacetic acid anticoagulated
      blood. Genotyping of the MMP2 (-1306C>T) and TIMP2 (-418 G>C) polymorphisms was
      performed using real-time polymerase chain reaction. RESULTS: Genotype
      distributions or allelic frequencies of MMP2 (-1306C>T) and TIMP2 (-418 G>C) did
      not significantly differ between patients with AMD and control subjects.
      Similarly, no significant differences in either genotype distributions or allelic
      frequencies of MMP2 (-1306C>T) and TIMP2 (-418 G>C) were found between dry and
      wet AMD. CONCLUSION: MMP2 (-1306C>T) and TIMP2 (-418 G>C) promoter variants are
      unlikely to have a major role in age-related macular degeneration risk
      susceptibility.

PMID- 23536956
TI  - Virological and clinical characterizations of respiratory infections in
      hospitalized children.
AB  - BACKGROUND: The purpose of this study was to determine the incidence and seasonal
      distribution of viral etiological agents and to compare their clinical
      manifestations and disease severity, including single and co infections. METHODS:
      Multiplex reverse-transcription PCR was performed for the detection of viruses in
      nasopharyngeal aspirat. Disease severity was grouped using a categorization index
      as very mild/mild, and moderate/severe. Clinical and laboratory characteristics
      of hospitalized children with viral respiratory tract infection were analyzed.
      RESULTS: Viral pathogens were detected in 103/155 (66.5%) of patients. In order
      of frequency, identified pathogens were respiratory syncytial virus (32.0%),
      adenovirus (26.2%), parainfluenza viruses type 1-4 (19.4%), rhinovirus (18.4%),
      influenza A and B (12.6%), human metapneumovirus (12.6%), coronavirus (2.9%), and
      bocavirus (0.9%). Coinfections were present in 21 samples. Most of the children
      had very mild (38.8%) and mild disease (37.9%). Severity of illness was not worse
      with coinfections. The most common discharge diagnoses were "URTI" with or
      without LRTI/asthma (n=58). Most viruses exhibited strong seasonal patterns.
      Leukocytosis (22.2%) and neutrophilia (36.6%) were most commonly detected in
      patients with adenovirus and rhinovirus (p<0.05). Monocytosis was the most
      remarkable finding in the patients (n=48, 53.3%), especially in patients with
      adenovirus (p<0.05). CONCLUSIONS: RSV and RhV were associated with higher
      severity of illness in hospitalized children. RSV found to account for half of
      LRTI hospitalizations. In AdV and FluA and B infections, fever lasted longer than
      in other viruses. Coinfections were detected in 21 of the patients. The presence
      of coinfections was not associated with increased disease severity.

PMID- 23536958
TI  - The role of ecological variation in driving divergence of sexual and non-sexual
      traits in the red-backed fairy-wren (Malurus melanocephalus).
AB  - BACKGROUND: Many species exhibit geographic variation in sexual signals, and
      divergence in these traits may lead to speciation. Sexual signals may diverge due
      to differences in ecology if the environment constrains signal production or
      transmission. Alternatively, sexual signals may diverge stochastically through
      sexual selection or genetic drift, with little environmental influence. To
      distinguish between these alternatives we quantified variation in two putative
      sexual signals--tail length and plumage color--and a suite of non-sexual
      morphometric traits across the geographic range of the red-backed fairy-wren
      (Malurus melanocephalus). We then tested for associations between these traits
      and a number of environmental variables using generalized dissimilarity models.
      RESULTS: Variation in morphometric traits was explained well by environmental
      variation, irrespective of geographic distance between sites. Among putative
      signals, variation in plumage color was best explained by geographic distance,
      whereas tail length was best explained by environmental variation. Divergence in
      male plumage color was not coincident with the boundary between genetic lineages,
      but was greatest across a contact zone located 300 km east of the genetic
      boundary. CONCLUSIONS: Morphometric traits describing size and shape have likely
      been subject to ecological selection and thus appear to track local environmental
      variation regardless of subspecies identity. Ecological selection appears to have
      also influenced the evolution of tail length as a signal, but has played a
      limited role in shaping geographic variation in plumage color, consistent with
      stochastic divergence in concert with Fisherian selection on this trait. The lack
      of coincidence between the genetic boundary and the contact zone between plumage
      types suggests that the sexual plumage signal of one subspecies has introgressed
      into the genetic background of the other. Thus, this study provides insight into
      the various ways in which signal evolution may occur within a species, and the
      geographic patterns of signal variation that can arise, especially following
      secondary contact.

PMID- 23536959
TI  - Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of
      metallothionein and nuclear factor (erythroid-derived 2)-like 2.
AB  - BACKGROUND: Cardiovascular diseases remain a leading cause of the mortality world
      wide, which is related to several risks, including the life style change and the
      increased diabetes prevalence. The present study was to explore the preventive
      effect of zinc on the pathogenic changes in the aorta. METHODS: A genetic type 1
      diabetic OVE26 mouse model was used with/without zinc supplementation for 3
      months. To determine gender difference either for pathogenic changes in the aorta
      of diabetic mice or for zinc protective effects on diabetes-induced pathogenic
      changes, both males and females were investigated in parallel by
      histopathological and immunohistochemical examinations, in combination of real
      time PCR assay. RESULTS: Diabetes induced significant increases in aortic
      oxidative damage, inflammation, and remodeling (increased fibrosis and wall
      thickness) without significant difference between genders. Zinc treatment of
      these diabetic mice for three months completely prevented the above pathogenic
      changes in the aorta, and also significantly up-regulated the expression and
      function of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a pivotal
      regulator of anti-oxidative mechanism, and the expression of metallothionein
      (MT), a potent antioxidant. There was gender difference for the protective effect
      of zinc against diabetes-induced pathogenic changes and the up-regulated levels
      of Nrf2 and MT in the aorta. CONCLUSIONS: These results suggest that zinc
      supplementation provides a significant protection against diabetes-induced
      pathogenic changes in the aorta without gender difference in the type 1 diabetic
      mouse model. The aortic protection by zinc against diabetes-induced pathogenic
      changes is associated with the up-regulation of both MT and Nrf2 expression.

PMID- 23536960
TI  - High-confidence de novo peptide sequencing using positive charge derivatization
      and tandem MS spectra merging.
AB  - De novo peptide sequencing holds great promise in discovering new protein
      sequences and modifications but has often been hindered by low success rate of
      mass spectra interpretation, mainly due to the diversity of fragment ion types
      and insufficient information for each ion series. Here, we describe a novel
      methodology that combines highly efficient on-tip charge derivatization and
      tandem MS spectra merging, which greatly boosts the performance of
      interpretation. TMPP-Ac-OSu (succinimidyloxycarbonylmethyl tris(2,4,6
      trimethoxyphenyl)phosphonium bromide) was used to derivatize peptides at N
      termini on tips to reduce mass spectra complexity. Then, a novel approach of
      spectra merging was adopted to combine the benefits of collision-induced
      dissociation (CID) and electron transfer dissociation (ETD) fragmentation. We
      applied this methodology to rat C6 glioma cells and the Cyprinus carpio and
      searched the resulting peptide sequences against the protein database. Then, we
      achieved thousands of high-confidence peptide sequences, a level that
      conventional de novo sequencing methods could not reach. Next, we identified
      dozens of novel peptide sequences by homology searching of sequences that were
      fully backbone covered but unmatched during the database search. Furthermore, we
      randomly chose 34 sequences discovered in rat C6 cells and verified them.
      Finally, we conclude that this novel methodology that combines on-tip positive
      charge derivatization and tandem MS spectra merging will greatly facilitate the
      discovery of novel proteins and the proteome analysis of nonmodel organisms. 

PMID- 23536961
TI  - Subphenotypes of mild-to-moderate COPD by factor and cluster analysis of
      pulmonary function, CT imaging and breathomics in a population-based survey.
AB  - INTRODUCTION: Classification of COPD is currently based on the presence and
      severity of airways obstruction. However, this may not fully reflect the
      phenotypic heterogeneity of COPD in the (ex-) smoking community. We hypothesized
      that factor analysis followed by cluster analysis of functional, clinical,
      radiological and exhaled breath metabolomic features identifies subphenotypes of
      COPD in a community-based population of heavy (ex-) smokers. METHODS: Adults
      between 50-75 years with a smoking history of at least 15 pack-years derived from
      a random population-based survey as part of the NELSON study underwent detailed
      assessment of pulmonary function, chest CT scanning, questionnaires and exhaled
      breath molecular profiling using an electronic nose. Factor and cluster analyses
      were performed on the subgroup of subjects fulfilling the GOLD criteria for COPD
      (post-BD FEV1/FVC < 0.70). RESULTS: Three hundred subjects were recruited, of
      which 157 fulfilled the criteria for COPD and were included in the factor and
      cluster analysis. Four clusters were identified: cluster 1 (n = 35; 22%): mild
      COPD, limited symptoms and good quality of life. Cluster 2 (n = 48; 31%): low
      lung function, combined emphysema and chronic bronchitis and a distinct breath
      molecular profile. Cluster 3 (n = 60; 38%): emphysema predominant COPD with
      preserved lung function. Cluster 4 (n = 14; 9%): highly symptomatic COPD with
      mildly impaired lung function. In a leave-one-out validation analysis an accuracy
      of 97.4% was reached. CONCLUSIONS: This unbiased taxonomy for mild to moderate
      COPD reinforces clusters found in previous studies and thereby allows better
      phenotyping of COPD in the general (ex-) smoking population.

PMID- 23536963
TI  - The effects of aromatherapy on nicotine craving on a U.S. campus: a small
      comparison study.
AB  - OBJECTIVES: To evaluate the effect of two inhaled essential oils (black pepper or
      angelica) on the nicotine habits of students, staff, and faculty on a U.S.
      college campus. DESIGN: Comparative study with pre-/post-test measures. SETTING:
      Community college in rural East Texas. PARTICIPANTS: Convenience sample of 20
      volunteers from the college community (students, faculty, and staff) who were
      regular (daily) users of nicotine (cigarettes, snuff, or chewing tobacco).
      INTERVENTIONS: Inhalation of one drop of essential oil on a tissue for 2 minutes
      when participant was craving nicotine. OUTCOME MEASURES: (1) Pre-inhalation
      journal recording of self-assessed level of craving for nicotine on a 0-10 scale,
      (2) post-inhalation journal recording of self-assessed level of craving for
      nicotine on a 0-10 scale, and (3) minutes that participant waited from start of
      inhalation until next use of tobacco. RESULTS: Both black pepper and angelica
      reduced the level of nicotine craving and allowed a longer delay before next use
      of tobacco. However, black pepper reduced the level of craving more than did
      angelica, and angelica allowed for a longer delay than did black pepper.
      CONCLUSIONS: Aromatherapy may be useful in nicotine withdrawal. Further studies
      are warranted.

PMID- 23536962
TI  - Expression of quiescin sulfhydryl oxidase 1 is associated with a highly invasive
      phenotype and correlates with a poor prognosis in Luminal B breast cancer.
AB  - INTRODUCTION: Quiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to
      form disulfide bonds in proteins. Tumor specific expression of QSOX1 has been
      reported for numerous tumor types. In this study, we investigate QSOX1 as a
      marker of breast tumor progression and evaluate the role of QSOX1 as it relates
      to breast tumor growth and metastasis. METHODS: Correlation of QSOX1 expression
      with breast tumor grade, subtype and estrogen receptor (ER) status was gathered
      through informatic analysis using the "Gene expression based Outcome for Breast
      cancer Online" (GOBO) web-based tool. Expression of QSOX1 protein in breast
      tumors tissue microarray (TMA) and in a panel of breast cancer cell lines was
      used to confirm our informatics analysis. To investigate malignant cell
      mechanisms for which QSOX1 might play a key role, we suppressed QSOX1 protein
      expression using short hairpin (sh) RNA in ER+ Luminal A-like MCF7, ER+ Luminal B
      like BT474 and ER- Basal-like BT549 breast cancer cell lines. RESULTS: GOBO
      analysis revealed high levels of QSOX1 RNA expression in ER+ subtypes of breast
      cancer. In addition, Kaplan Meyer analyses revealed QSOX1 RNA as a highly
      significant predictive marker for both relapse and poor overall survival in
      Luminal B tumors. We confirmed this finding by evaluation of QSOX1 protein
      expression in breast tumors and in a panel of breast cancer cell lines.
      Expression of QSOX1 in breast tumors correlates with increasing tumor grade and
      high Ki-67 expression. Suppression of QSOX1 protein slowed cell proliferation as
      well as dramatic inhibition of MCF7, BT474 and BT549 breast tumor cells from
      invading through MatrigelTM in a modified Boyden chamber assay. Inhibition of
      invasion could be rescued by the exogenous addition of recombinant QSOX1. Gelatin
      zymography indicated that QSOX1 plays an important role in the function of MMP-9,
      a key mediator of breast cancer invasive behavior. CONCLUSIONS: Taken together,
      our results suggest that QSOX1 is a novel biomarker for risk of relapse and poor
      survival in Luminal B breast cancer, and has a pro-proliferative and pro-invasive
      role in malignant progression partly mediated through a decrease in MMP-9
      functional activity.

PMID- 23536964
TI  - Regression of ductal carcinoma in situ after treatment with acupuncture.
AB  - This report describes a case of ductal carcinoma in situ (DCIS) that regressed
      after treatment with acupuncture, Chinese herbs, and other complementary and
      alternative medicine (CAM). The natural history of DCIS remains to be elucidated,
      and it is unclear whether all DCIS cases progress to invasive breast cancer.
      Surgery plus radiation therapy or mastectomy is recommended for women in whom
      this potentially nonprogressive cancer is detected. This case supports the
      developing trend toward active surveillance in lieu of breast-disfiguring surgery
      and offers evidence that CAM therapies may be of value in preventing progression
      of DCIS to invasive breast cancer.

PMID- 23536965
TI  - Ultra-rapid elimination of biofilms via the combustion of a nanoenergetic
      coating.
AB  - BACKGROUND: Biofilms occur on a wide variety of surfaces including metals,
      ceramics, glass etc. and often leads to accumulation of large number of various
      microorganisms on the surfaces. This biofilm growth is highly undesirable in most
      cases as biofilms can cause degradation of the instruments and its performance
      along with contamination of the samples being processed in those systems. The
      current "offline" biofilm removal methods are effective but labor intensive and
      generates waste streams that are toxic to be directly disposed. We present here a
      novel process that uses nano-energetic materials to eliminate biofilms in < 1
      second. The process involves spray-coating a thin layer of nano-energetic
      material on top of the biofilm, allowing it to dry, and igniting the dried
      coating to incinerate the biofilm. RESULTS: The nanoenergetic material is a
      mixture of aluminum (Al) nanoparticles dispersed in a THV-220A (fluoropolymer
      oxidizer) matrix. Upon ignition, the Al nanoparticles react with THV-220A
      exothermically, producing high temperatures (>2500 K) for an extremely brief
      period (~100 ms) that destroys the biofilm underneath. However, since the total
      amount of heat produced is low (~0.1 kJ/cm2), the underlying surface remains
      undamaged. Surfaces with biofilms of Pseudomonas aeruginosa initially harboring ~
      10(7) CFU of bacteria /cm2 displayed final counts of less than 5 CFU/cm2 after
      being subjected to our process. The byproducts of the process consist only of
      washable carbonaceous residue and gases, making this process potentially
      inexpensive due to low toxic-waste disposal costs. CONCLUSIONS: This novel method
      of biofilm removal is currently in the early stage of development. However, it
      has potential to be used in offline biofilm elimination as a rapid, easy and
      environmentally friendly method.

PMID- 23536966
TI  - Experimental and theoretical investigations of the dissociation energy (D0) and
      dynamics of the water trimer, (H2O)3.
AB  - We report a joint experimental-theoretical study of the predissociation dynamics
      of the water trimer following excitation of the hydrogen bonded OH-stretch
      fundamental. The bond dissociation energy (D0) for the (H2O)3 -> H2O + (H2O)2
      dissociation channel is determined from fitting the speed distributions of
      selected rovibrational states of the water monomer fragment using velocity map
      imaging. The experimental value, D0 = 2650 +/- 150 cm(-1), is in good agreement
      with the previously determined theoretical value, 2726 +/- 30 cm(-1), obtained
      using an ab initio full-dimensional potential energy surface (PES) together with
      Diffusion Monte Carlo calculations [ Wang ; Bowman . J. Chem. Phys. 2011 , 135 ,
      131101 ]. Comparing this value to D0 of the dimer places the contribution of
      nonpairwise additivity to the hydrogen bonding at 450-500 cm(-1). Quasiclassical
      trajectory (QCT) calculations using this PES help elucidate the reaction
      mechanism. The trajectories show that most often one hydrogen bond breaks first,
      followed by breaking and re-forming of hydrogen bonds (often with different
      hydrogen bonds breaking) until, after many picoseconds, a water monomer is
      finally released. The translational energy distributions calculated by QCT for
      selected rotational levels of the monomer fragment agree with the experimental
      observations. The product translational and rotational energy distributions
      calculated by QCT also agree with statistical predictions. The availability of
      low-lying intermolecular vibrational levels in the dimer fragment is likely to
      facilitate energy transfer before dissociation occurs, leading to statistical
      like product state distributions. 

PMID- 23536967
TI  - Nasal and perirectal colonization of vancomycin sensitive and resistant
      enterococci in patients of paediatrics ICU (PICU) of tertiary health care
      facilities.
AB  - BACKGROUND: Enterococci normally inhabit the intestinal tract of humans and are
      also a potential pathogen in causing nosocomial infections. The increase in
      antibiotic resistance and transfer of antibiotic resistance gene to
      Staphylococcus aureus (S. aureus) due to co-colonization has increased its
      importance in research. The aim of the study was to evaluate local epidemiology
      of nasal and rectal colonization with Enterococcus faecalis (E. faecalis) and
      Enterococcus faecium (E. faecium) in patients of Paediatrics Intensive Care Unit
      (PICU) and correlation with clinical and socioeconomic factors. METHODS: The
      nasal and perirectal swab samples were collected from 110 patients admitted in
      PICUs of three tertiary care hospitals of Rawalpindi Medical College, Pakistan.
      The identification of enterococci was done by biochemical tests and by PCR for
      ddl, vanA and vanB genes. Antibiotic susceptibility testing was performed by disc
      diffusion and MICs were determined for vancomycin, tetracycline, ciprofloxacin
      and oxacillin only. RESULTS: Out of 220 nasal and perirectal samples, 09
      vancomycin-resistant enterococci (VRE) and 76 vancomycin-susceptible enterococci
      (VSE), consisting of 40 E. faecalis and 45 E. faecium were isolated. PCR
      successfully identified both species with ddl primers and VRE with vanA primer.
      With disc diffusion method, all isolates were resistant to most of the
      antibiotics tested except linezolid, quinupristin/dalfopristin, teicoplanin and
      vancomycin. VRE showed resistance to teicoplanin and vancomycin both and none was
      resistant to linezolid and quinupristin/dalfopristin. Generally, E. faecium
      isolates were more resistant than E. faecalis. MICs of vancomycin for nasal and
      perirectal VRE were 512 mg/L and 64 to 512 mg/L respectively. VRE were more in
      patients with prolonged hospitalization, from urban localities and those having
      pneumonia. CONCLUSION: Present study reveals high colonization and antibiotic
      resistance in enterococcal isolates from nasal and perirectal area. Nasal
      colonization by enterococci in PICU is more alarming as VRE may cause infection
      and can transfer this resistance gene to other microorganisms like S. aureus.

PMID- 23536968
TI  - Novel approaches to minimize ventilator-induced lung injury.
AB  - Despite over 40 years of research, there is no specific lung-directed therapy for
      the acute respiratory distress syndrome (ARDS). Although much has evolved in our
      understanding of its pathogenesis and factors affecting patient outcome,
      supportive care with mechanical ventilation remains the cornerstone of treatment.
      Perhaps the most important advance in ARDS research has been the recognition that
      mechanical ventilation, although necessary to preserve life, can itself aggravate
      or cause lung damage through a variety of mechanisms collectively referred to as
      ventilator-induced lung injury (VILI). This improved understanding of ARDS and
      VILI has been important in designing lung-protective ventilatory strategies aimed
      at attenuating VILI and improving outcomes. Considerable effort has been made to
      enhance our mechanistic understanding of VILI and to develop new ventilatory
      strategies and therapeutic interventions to prevent and ameliorate VILI with the
      goal of improving outcomes in patients with ARDS. In this review, we will review
      the pathophysiology of VILI, discuss a number of novel physiological approaches
      for minimizing VILI, therapies to counteract biotrauma, and highlight a number of
      experimental studies to support these concepts.

PMID- 23536969
TI  - Randomized clinical trials to identify optimal antibiotic treatment duration.
AB  - BACKGROUND: Antibiotic resistance is a major barrier to the continued success of
      antibiotic treatment. Such resistance is often generated by overly long durations
      of antibiotic treatment. A barrier to identifying the shortest effective
      treatment duration is the cost of the sequence of clinical trials needed to
      determine shortest optimal duration. We propose a new method to identify the
      optimal treatment duration of an antibiotic treatment regimen. METHODS: Subjects
      are randomized to varying treatment durations and the cure proportions of these
      durations are linked using a logistic regression model, making effective use of
      information across all treatment duration groups. In this paper, Monte Carlo
      simulation is used to evaluate performance of such a model. RESULTS: Using a
      hypothetical dataset, the logistic regression model is seen to provide increased
      precision in defining the point estimate and confidence interval (CI) of the cure
      proportion at each treatment duration. When applied to the determination of non
      inferiority, the regression model allows identification of the shortest duration
      meeting the predefined non-inferiority margin. CONCLUSIONS: This analytic
      strategy represents a practical way to develop shortened regimens for
      tuberculosis and other infectious diseases. Application of this strategy to
      clinical trials of antibiotic therapy could facilitate decreased antibiotic
      usage, reduce cost, minimize toxicity, and decrease the emergence of antibiotic
      resistance.

PMID- 23536970
TI  - Use of enzymatic tools for biomonitoring inorganic pollution in aquatic
      sediments: a case study (Bor, Serbia).
AB  - BACKGROUND: Sediment bacterial communities are key players in biogeochemical
      cycling of elements in the aquatic environment. Copper mining, smelting, and
      processing operations located in Bor area (Serbia) are major environmental hot
      spots in the lower Danube Basin and Western Balkans. In the present study, we
      evaluate the influence of trace element (TE) concentration in sediments and
      physico-chemical properties of water on sediment microbial communities in water
      streams adjacent to the Copper Smelter Complex Bor (RTB Bor, Serbia). The degree
      to which metabolic activities of bacterial biota inhabiting differently polluted
      sites is inhibited by inorganic pollution were compared using selected enzymatic
      bioindicators. RESULTS: Cu, Zn, Pb, and As concentrations systematically exceeded
      the target values for metal loadings in aquatic sediments. Water electrical
      conductivity (WEC) followed the same pattern of spatial variation, irrespective
      of season. Interestingly, the most intense enzymatic activity occurred at the
      reference site although this site showed the greatest TE levels in aquatic
      sediments. Catalase activity (CA), potential dehydrogenase activity (PDA), actual
      dehydrogenase activity (ADA), urease activity (UA), and phosphatase activity (PA)
      in aquatic sediments displayed heterogeneous patterns of spatio-temporal
      variation. Inorganic pollution greatly affected CA, ADA, and PDA, but much less
      so UA and PA. Canonical correlation analysis showed that pH and WEC were the
      strongest determinants of enzymatic activity in bacterial biota, with the latter
      variable being reversely correlated with the enzymatic indicator of sediment
      quality (EISQ). The median values of EISQ increased with distance from the major
      sources of pollution. In addition, it was found that sites with different degrees
      of inorganic pollution can be appropriately classified by applying cluster
      analysis to EISQ, TE levels in sediments, and physico-chemical properties of
      water. CONCLUSIONS: Because EISQ can precisely identify changes in overall
      enzymatic activity of sediment bacterial communities, this enzymatic bioindicator
      has a great potential for biomonitoring the current status of inorganic pollution
      in aquatic ecosystems.

PMID- 23536972
TI  - Effect of food intake on the pharmacokinetics of sarpogrelate and its active
      metabolite following oral administration to beagle dogs.
AB  - 1. The objectives of this study were to develop a pharmacokinetic model for
      sarpogrelate and its metabolite M-1 and to identify the effect of food on
      sarpogrelate and M-1 pharmacokinetics in beagle dogs. 2. A single 100 mg oral
      dose of sarpogrelate was administered to fasted and fed beagle dogs and the
      plasma concentrations of sarpogrelate and M-1 were measured simultaneously by
      liquid chromatography tandem mass spectrometry. The resultant data were analyzed
      by modeling approaches using ADAPT5. 3. The plasma concentration time course of
      sarpogrelate and M-1 were described using a parent-metabolite compartment model
      with first-order absorption and elimination. The systemic exposure of
      sarpogrelate and its metabolite after the administration of a single 100 mg oral
      dose was significantly decreased under the fed condition compared to that under
      the fasting condition. Modeling approaches have sufficiently explained the food
      effect of sarpogrelate, i.e. an increased Vc and decreased Ka, in fed dogs. The
      food effect of sarpogrelate was due to its pH-dependent dissolution. 4. These
      findings suggest that food intake affects both the rate and extent of absorption
      of sarpogrelate, and that the pharmacological effect of sarpogrelate can differ
      significantly according to food intake.

PMID- 23536973
TI  - Injection of ropivacaine into the subarachnoid changes the ultrastructure and
      proteome of the rat spinal cord.
AB  - 1. In the present study, we investigated the impact of 1.0% ropivacaine on the
      ultrastructure and proteome of the rat spinal cord. 2. Rats received three
      injections (90-min intervals, 0.2 mL/kg) of 0.9% NaCl, 0.5% ropivacaine or 1.0%
      ropivacaine via an implanted intrathecal catheter. Transmission electron
      microscopy was performed to exam the ultrastructure of the spinal cord. Two
      dimensional electrophoresis followed by mass spectrometry identification were
      carried out to investigate the proteome. 3. In the rats administered 1.0%
      ropivacaine, deformed organelles, detached myelinated nerve fiber layer, and
      incomplete inner and outer shaft membranes were observed in the spinal cord and
      posterior root shrunken nuclei. Furthermore, in the rat spinal cord 1.0%
      ropivacaine induced the down-regulation of voltage-dependent anion channel 2
      (VDAC2) and mitochondrial pyruvate dehydrogenase subunit alpha (ODPA), the
      upregulation of myelin basic protein (MBP), the disappearance of myelin
      transcription factor 1 (MYT1) and the appearance of heat shock protein 25
      (HSP25). Little change was observed in the 0.5% ropivacaine or control groups. 4.
      Our results suggest that 1.0% ropivacaine treatment led to neurotoxicity, as
      shown by ultrastructural and proteomic changes in the rat spinal cord. Specific
      proteins were identified that are implicated in 1.0% ropivacaine-induced
      neurotoxicity.

PMID- 23536974
TI  - Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to
      ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising
      from anesthetics.
AB  - Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide
      antidote; therefore, the antidotal utility of this organic nitrite compared with
      sodium nitrite was investigated. To facilitate a quantitative comparison, doses
      of both sodium nitrite and isoamyl nitrite were given intraperitoneally in
      equimolar amounts to sublethally cyanide-challenged mice. Righting recovery from
      the knockdown state was clearly compromised in the isoamyl nitrite-treated
      animals, the effect being attributable to the toxicity of the isoamyl alchol
      produced during hydrolysis of the isoamyl nitrite to release nitrite anion.
      Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to
      ameliorate sublethal cyanide toxicity, when provided to mice after the toxic
      dose, by the more rapid recovery of righting ability compared to that of the
      control animals given only the toxicant. Aerosolized sodium nitrite has thus been
      shown by these experiments to have promise as a better alternative to organic
      nitrites for development as an inhaled cyanide antidote. The inhaled sodium
      nitrite led to the production of NO in the bloodstream as determined by the
      appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin.
      The aerosol delivery was performed in an unmetered inhalation chamber, and in
      this study, no attempt was made to optimize the procedure. It is argued that
      administration of an effective inhaled aqueous sodium nitrite dose in humans is
      possible, though just beyond the capability of current individual metered-dose
      inhaler designs, such as those used for asthma. Finally, working at slightly
      greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia
      leads to significantly prolonged survival compared to that of unanesthetized
      animals and that (ii) the antidotal activity of nitrite anion was completely
      abolished under anesthesia. Plausible explanations for these effects in mice and
      their practical consequences in relation to testing putative cyanide antidotes
      are discussed.

PMID- 23536975
TI  - The General Assessment of Personality Disorder (GAPD): factor structure,
      incremental validity of self-pathology, and relations to DSM-IV personality
      disorders.
AB  - Recent developments in the classification of personality disorder, especially
      moves toward more dimensional systems, create the need to assess general
      personality disorder apart from individual differences in personality pathology.
      The General Assessment of Personality Disorder (GAPD) is a self-report
      questionnaire designed to evaluate general personality disorder. The measure
      evaluates 2 major components of disordered personality: self or identity problems
      and interpersonal dysfunction. This study explores whether there is a single
      factor reflecting general personality pathology as proposed by the Diagnostic and
      Statistical Manual of Mental Disorders (5th ed.), whether self-pathology has
      incremental validity over interpersonal pathology as measured by GAPD, and
      whether GAPD scales relate significantly to Diagnostic and Statistical Manual of
      Mental Disorders (4th ed. [DSM-IV]) personality disorders. Based on responses
      from a German psychiatric sample of 149 participants, parallel analysis yielded a
      1-factor model. Self Pathology scales of the GAPD increased the predictive
      validity of the Interpersonal Pathology scales of the GAPD. The GAPD scales
      showed a moderate to high correlation for 9 of 12 DSM-IV personality disorders. 

PMID- 23536976
TI  - Virologic, immunologic and clinical response of infants to antiretroviral therapy
      in Kampala, Uganda.
AB  - BACKGROUND: Antiretroviral therapy (ART) is known to save lives. Among HIV
      infected infants living in resource constrained settings, the short and long term
      benefits of ART are only partially known. This study was designed to determine
      the virologic, immunologic and clinical outcomes of antiretroviral therapy in a
      cohort of HIV-infected infants receiving care from an outpatient clinic in
      Kampala, Uganda. METHODS: A prospective cohort of HIV-infected infants receiving
      treatment at the Baylor-Uganda clinic was analyzed. Patients were diagnosed,
      enrolled and followed up at the clinic. HIV viral load, CD4 cell counts and
      clinical progress were assessed during follow-up. Descriptive statistical
      analysis and logistic regression modeling to determine predictors of treatment
      success were conducted. RESULTS: Of 91 HIV-infected infants enrolled into the
      cohort, 53 (58.2%) infants were female; 43 (47.3%) were 6 months of age or
      younger, and 50 (55.6%) had advanced HIV/AIDS disease (Clinical stage 3 or 4).
      Eighty four infants started ART and 78 (92.9%) completed 6 months of treatments.
      Fifty six (71.8%) infants attained virologic suppression by month-6 of ART, and
      at month-12 of ART, the cumulative probability of attaining viral suppression was
      83.1%. None of the baseline infant factors (age, sex, WHO stage, CD4 cell
      percent, weight for age, or height for age z-score) predicted treatment success.
      There was an increase in CD4 cells from a baseline mean of 23% to 30% at month-6
      of treatment (p<0.001) and by month-24 of ART, the mean CD4 percent was 36%. A
      total of 7 patients died while on ART and another 7 experienced adverse events
      that were related to treatment. CONCLUSION: Our results show that, even among
      very young patients from resource constrained settings, ART dramatically
      suppresses HIV replication, allows immune recovery and clinical improvement, and
      is safe. However, baseline characteristics do not predict recovery in this age
      group.

PMID- 23536977
TI  - Deferoxamine preconditioning potentiates mesenchymal stem cell homing in vitro
      and in streptozotocin-diabetic rats.
AB  - OBJECTIVE: Today, cell therapy is considered a promising alternative in treatment
      of several diseases such as type 1 diabetes. Loss of transplanted stem cell and
      more importantly scarcity in the number of cells reaching to target tissue is a
      major obstacle in cell therapy. There is evidences showing that deferoxamine
      (DFO), an iron chelator, increases the mobilization and homing of progenitor
      cells through increasing the stability of hypoxia-inducible factor 1alpha (HIF
      1alpha) protein. In this study, the effect of DFO on some factors involved in
      homing of bone marrow-derived mesenchymal stem cell was investigated, and the
      other objectives of this research were to determine whether DFO is able to
      increase migration and subsequent homing of mesenchymal stem cell (MSCs) both in
      vitro and in vivo in streptozotocin-diabetic rats. RESEARCH DESIGN AND METHODS:
      MSCs were treated by DFO in minimal essential medium alpha (alphaMEM) for 24 h.
      The expression and localization of HIF-1alpha were evaluated by western blotting
      and immunocytochemistry. The expression of C-X-C chemokine receptor type 4 (CXCR
      4) and chemokine receptor 2 (CCR2) were assessed by western blotting and RT-PCR.
      The activity of matrix metalloproteinases (MMP) -2 and -9 were measured by
      gelatin zymography. Finally, in vitro migration of MSCs toward different
      concentrations of stromal cell-derived factor and monocyte chemotactic protein-1
      were also evaluated. To demonstrate the homing of MSCs in vivo, DFO-treated
      chloromethyl-benzamidodialkylcarbocyanine-labeled MSCs were injected into the
      tail vein of rats, and the number of stained MSCs reaching to the pancreas were
      determined after 24 h. RESULTS: In DFO-treated MSCs, expression of HIF-1alpha (p
      < 0.001), CXCR4 (p < 0.001), CCR2 (p < 0.001), and the activity of MMP-2 (p <
      0.01) and MMP-9 (p < 0.05) were significantly increased compared to control
      groups. Elevation of HIF-1alpha, upregulation of CXCR4/CCR2 and higher activity
      of MMP-2/MMP-9 in DFO-treated MSCs were reversed by 2-methoxyestradiol (2-ME; 5
      MUmol), a HIF-1alpha inhibitor. The in vitro migrations as well as in vivo homing
      of DFO-treated MSCs were also significantly higher than control groups (p <
      0.05). CONCLUSIONS: Preconditioning of MSCs by DFO prior to transplantation could
      increase homing of MSCs through affecting some chemokine receptors as well as
      proteases involved and eventually improving the efficacy of cell therapy.

PMID- 23536978
TI  - What are we measuring?

PMID- 23536980
TI  - Risk factors for respiratory syncytial virus illness among patients with chronic
      obstructive pulmonary disease.
AB  - Respiratory syncytial virus (RSV), although not typically considered an important
      pathogen in adults, may cause acute exacerbation of chronic obstructive pulmonary
      disease (COPD). It is unclear which COPD patients are at highest risk for
      developing serious RSV illness. Our objective was to identify risk factors for
      RSV illness among adult patients with COPD. We conducted a pooled analysis of
      data from COPD patients in 2 previously published longitudinal studies that
      examined RSV infection in high risk adults for <= 2 RSV seasons. Risk factors for
      RSV illness studied included age, sex, race, smoking status, exposure to
      children, home oxygen use, inhaled or oral steroid use, instrumental activities
      of daily living scores, and co-morbid conditions. Outcomes studied included
      symptomatic and medically attended RSV illness. Logistic regression was used to
      identify significant risk factors for RSV illness among older adults with COPD.
      Among 379 patients with COPD, the rate of symptomatic RSV illness was 11.1%
      (42/379); almost half (20/42) of whom required medical attention. In
      multivariable analyses, congestive heart failure (odds ratio [OR] = 4.18; 95% CI:
      1.38, 12.69) and exposure to children (OR = 2.38; 95% CI: 1.03, 5.51) were risk
      factors for symptomatic RSV illness. Congestive heart failure (OR = 4.16; 95% CI:
      1.02, 17.01) was the only significant risk factor for developing medically
      attended RSV illness. Exposure to children and congestive heart failure are risk
      factors for RSV illness among adult patients with COPD. Future prospective, well
      designed studies are needed to corroborate these findings and examine other risk
      factors, including history of exacerbations.

PMID- 23536981
TI  - Isolation of Arcobacter species in water buffaloes (Bubalus bubalis).
AB  - This is the first report of Arcobacter spp. in rectal fecal samples from healthy
      water buffaloes (Bubalus bubalis) reared on a dairy farm. Arcobacter species were
      isolated after enrichment, and isolates were identified at species level by
      multiplex-polymerase chain reaction assay. Thirty samples were examined and
      Arcobacter spp. were isolated from 96.7% of water buffaloes tested: 38 Arcobacter
      spp. isolates were obtained, with A. cryaerophilus as the dominant species
      followed by A. butzleri and A. skirrowii. Nine animals (31%) were colonized by
      more than one Arcobacter species. The present study indicates that water
      buffaloes can harbor a variety of Arcobacter spp. and that healthy buffaloes may
      act as hosts. Water buffalo fecal shedding of Arcobacter spp. may be of
      significance to human health, considering the potential fecal contamination
      during harvesting of raw milk and slaughtering.

PMID- 23536982
TI  - Pathogenic psychrotolerant sporeformers: an emerging challenge for low
      temperature storage of minimally processed foods.
AB  - Sporeforming bacteria are a significant problem in the food industry as they are
      ubiquitous in nature and capable of resisting inactivation by heat and chemical
      treatments designed to inactivate them. Beyond spoilage issues, psychrotolerant
      sporeformers are becoming increasingly recognized as a potential hazard given the
      ever-expanding demand for refrigerated processed foods with extended shelf-life.
      In these products, the sporeforming pathogens of concern are Bacillus cereus,
      Bacillus weihenstephanensis, and Clostridium botulinum type E. This review
      article examines the foods, conditions, and organisms responsible for the food
      safety issue caused by the germination and outgrowth of psychrotolerant
      sporeforming pathogens in minimally processed refrigerated foods.

PMID- 23536983
TI  - Use of bioluminescent Escherichia coli to determine retention during the life
      cycle of the housefly, Musca domestica (Diptera: Muscidae, L).
AB  - Researchers have documented that the housefly (Musca domestica) can serve as a
      vector for the spread of foodborne pathogens to livestock, food, and humans. Most
      studies have investigated Musca domestica as a vector only after the fly comes
      into contact or consumes the pathogen as an adult. The objective of this study
      was to determine whether the larvae of Musca domestica could ingest Escherichia
      coli from bovine manure and whether the E. coli could survive the metamorphosis
      process and be transmitted. Larvae (n=960) were incubated in sterilized bovine
      manure inoculated with 0, 3, 5, and 8 log10 colony-forming units (CFU)/mL of
      bioluminescent E. coli for 24 (larvae stage), 48 (larvae stage), 120 (pupae
      stage), and 192 h (adult stage). Larvae incubated for 24 h in bovine manure
      possessed 0.0, 2.7, 2.9, and 3.5 log(10) CFU/mL of E. coli, from inoculated with
      0, 3, 5, and 8 log(10) CFU/mL of E. coli, respectively. Concentrations of E. coli
      within the pupae were 0.0, 1.7, 1.9, and 2.2 log(10) CFU/mL for each inoculation
      concentration, respectively. Flies that emerged from the pupae stage contained
      0.0, 1.3, 2.2, and 1.7 log(10) CFU/mL of E. coli from larvae incubated in manure
      inoculated with concentrations of E. coli, respectively. These results suggest
      the housefly can emerge with quantities of E. coli. While this was an
      enteropathogenic E. coli (EPEC), these data may suggest that if the fly is
      capable of retaining similar concentrations of an enterohemorrhagic E. coli
      (EHEC), these concentrations may be capable of initiating illness in humans.
      Furthermore, the E. coli concentration within and on adult flies is related to
      environmental exposure. It must be noted that larvae were incubated in sterilized
      bovine manure, and there was no other bacterial competition for the E. coli.
      Thus, the rate of positive flies and concentrations present when flies emerged
      may vary under more realistic conditions.

PMID- 23536984
TI  - Anisakiasis in China: the first clinical case report.
AB  - Anisakiasis is a parasitic disease acquired by humans when ingesting raw or
      undercooked fish infected with L3 larvae of the nematode genus Anisakis or
      Pseudoterranova. Here we report the first case of human anisakiasis in China. The
      patient, male, 56 years old, Dalian citizen, was admitted into the hospital with
      vomiting, peripheral umbilicus and abdominal distension, and frequent mucous
      diarrhea. The patient was examined using an electronic gastroscope, which
      displayed a parasite residing in the stomach, and subsequently gastroscope
      assisted surgery was implemented. A white round worm was removed from the patient
      and stained. It was identified as L3 larvae of Anisakis. After the removal of the
      L3 larvae of Anisakis, the inflammation symptoms disappeared. As the first report
      of clinical case of Anisakis infection in China, the morphology of L3 Anisakis
      larvae from the patient is described and discussed. We conclude that anisakiasis
      should be considered in patients who have a habit of eating raw fish and who
      display associated symptoms.

PMID- 23536985
TI  - Role of capsular polysaccharides and lipooligosaccharides in Campylobacter
      surface properties, autoagglutination, and attachment to abiotic surfaces.
AB  - The role of capsular polysaccharides and lipooligosaccharides in cell surface
      hydrophobicity, surface charge, autoagglutination (AAG), and attachment to
      abiotic surfaces of three strains of Campylobacter jejuni and one strain of C.
      coli were investigated. This was achieved by removal of capsular polysaccharides
      and truncation of lipooligosaccharides core oligosaccharides by inactivation of
      the kpsE and waaF genes, respectively. The mutants and the wild-type strains were
      compared after growth under planktonic (broth) and sessile (agar) conditions.
      Cells grown as planktonic cultures showed a significantly (p<0.05) higher degree
      of hydrophobicity and AAG activity but differed from their sessile counterparts
      with respect to surface charge and attachment counts, depending on the strain.
      These results suggest that prior mode of growth affects the surface properties
      and attachment of Campylobacter in a strain-dependent manner. There were no
      significant (p>0.05) differences between the three C. jejuni strains and their
      DeltakpsE and DeltawaaF mutants with respect to all traits tested. Inactivation
      of the kpsE gene significantly (p<0.05) reduced the surface charge of the C. coli
      strain from ~-10 to ~-6 mV and increased its AAG activity, while disruption of
      the waaF gene significantly (p<0.05) increased its surface hydrophobicity by >8
      degrees  and decreased the numbers of cells attaching to stainless steel and
      glass by ~0.5 log/cm2. These results suggest that surface polysaccharides may
      influence the surface properties and attachment to abiotic surfaces of C. coli
      but not C. jejuni. This suggestion, however, requires further investigation using
      a larger number of strains of both species.

PMID- 23536986
TI  - Regional distribution of two dairy-associated Salmonella enterica serotypes.
AB  - Salmonella enterica is a zoonotic pathogen that is often associated with dairy
      farms. The organism can cause disease in cows but is also frequently shed in
      large numbers by dairy cows that are asymptomatic. Long-term asymptomatic
      infections with serotypes Cerro and Kentucky were previously identified in cows
      on a 100-head dairy farm in Pennsylvania, United States (focal dairy). Milk
      filters were collected from farms within 30 miles of the focal dairy to determine
      whether the infections by Cerro and Kentucky were limited to the focal dairy or
      whether the infection might be more regional in nature. Analysis of milk filters
      showed that Cerro and Kentucky were widespread in the surrounding region with 16
      of 39 farms (41%) positive for one or both serotypes. Pulsed-field gel
      electrophoresis showed that the milk filter Kentucky strains shared >90%
      similarity with strains from the focal dairy and from local streams. Although
      there was more variation between Cerro strains (>80% similarity), most milk
      filter Cerro isolates from most milk filters were highly similar (>90%) to
      strains isolated from the focal dairy and local streams. In this intensely dairy
      farmed region, Salmonella infection of dairy cows appears to be regional in
      nature, a fact that will impact efforts to control these pathogens.

PMID- 23536987
TI  - Anisakid nematodes of Greenland halibut Reinhardtius hippoglossoides from the
      Barents Sea.
AB  - Parasitic nematodes from the body cavity of 94 Greenland halibut (Reinhardtius
      hippoglossoides) caught in the Barents Sea were examined. Nematode species were
      identified using both morphological and molecular methods. Four morphospecies
      were found: Anisakis simplex s.l., Contracaecum osculatum s.l., Pseudoterranova
      decipiens s.l., and Hysterothylacium aduncum. The most prevalent were C.
      osculatum s.l. (89.4%) and A. simplex s.l. (86.2%). Mean intensities for these 2
      species were 7.8 and 45.2, respectively. The number of parasites was directly
      proportional to the fish length. The following 6 parasite species, including 3
      cryptic species of Contracaecum sp., were identified using molecular methods: A.
      simplex sensu stricto, C. osculatum A, C. osculatum B and C (the last 2 as host
      records for halibut), Pseudoterranova bulbosa, and H. aduncum. Mixed infections
      of C. osculatum A, B, and C were observed.

PMID- 23536988
TI  - Zebrafish model for the genetic basis of X-linked retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) affects 1/4000 individuals in most populations, and X
      linked RP (XLRP) is one of the most severe forms of human retinal degeneration.
      Mutations in both the retinitis pigmentosa GTPase regulator (RPGR) gene and
      retinitis pigmentosa 2 (RP2) gene account for almost all cases of XLRP. The
      functional roles of both RPGR and RP2 in the pathogenesis of XLRP are unclear.
      Due to the surprisingly high degree of functional conservation between human
      genes and their zebrafish orthologues, the zebrafish has become an important
      model for human retinal disorders. In this brief review, we summarize the
      functional characterization of XLRP-causing genes, RPGR and RP2, in zebrafish,
      and highlight recent studies that provide insight into the cellular functions of
      both genes. This will not only shed light on disease mechanisms in XLRP but will
      also provide a solid platform to test RP-causing mutants before proposing XLRP
      gene therapy trials.

PMID- 23536989
TI  - Bigh3 is upregulated in regenerating zebrafish fin.
AB  - Zebrafish is a good model for studying regeneration because of the rapidity with
      which it occurs. Better understanding of this process may lead in the future to
      improvement of the regenerating capacity of humans. Signaling factors are the
      second largest category of genes, regulated during regeneration after the
      regulators of wound healing. Major developmental signaling pathways play a role
      in this multistep process, such as Bmp, Fgf, Notch, retinoic acid, Shh, and Wnt.
      In the present study, we focus on TGF-beta-induced genes, bigh3 and bambia. Bigh3
      encodes keratoepithelin, a protein first identified as an extracellular matrix
      protein reported to play a role in cell adhesion, as well as in cornea formation
      and osteogenesis. The expression of bigh3 in zebrafish fins has previously been
      reported. Here we demonstrate that tgf-b1 and tgf-b3 mRNA reacted with delay,
      first showing no regulation at 3 dpa, followed by upregulation at 4 and 5 dpa.
      Tgf-b1, tgf-2, and tgf-brII mRNA were back to normal levels at 10 dpa. Only tgf
      b3 mRNA was still upregulated at that time. Bigh3 mRNA followed the upregulation
      of tgf-b1, while bambia mRNA behaved similarly to tgf-b2 mRNA. We show that
      upregulation of bigh3 and bambia mRNA correlated with the process of fin
      regeneration and regulation of TGF-b signaling, suggesting a new role for these
      proteins.

PMID- 23536990
TI  - The CRISPR system--keeping zebrafish gene targeting fresh.
AB  - We are entering a new era in our ability to modify and edit the genomes of model
      organisms. Zinc finger nucleases (ZFNs) opened the door to the first custom
      nuclease-targeted genome engineering in the late 1990s. However, ZFNs remained
      out of reach for most research labs because of the difficulty of production, high
      costs, and modest efficacy in many applications. Transcription activator-like
      effector nucleases (TALENs) were built upon a DNA binding system discovered in a
      group of plant bacterial pathogens and broadened custom nuclease technology,
      showing significant improvements in both targeting flexibility and efficiency.
      Perhaps most importantly, TALENs are open source and easy to produce, providing
      zebrafish laboratories around the world with affordable tools that can be made in
      house rapidly, at low cost, and with reliably high activity. Now a new system for
      targeted genome engineering derived from the CRISPR/Cas system in eubacteria and
      archaea promises to simplify this process further. Together, these tools will
      help overcome many of the bottlenecks that have constrained gene targeting in
      zebrafish, paving the way for advanced genome engineering applications in this
      model teleost.

PMID- 23536991
TI  - Construct validity of the Italian version of the Mayer-Salovey-Caruso Emotional
      Intelligence Test (MSCEIT) v2.0.
AB  - In 2 studies, we assessed the construct validity of the Italian version of the
      Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) version 2.0. In Study
      1, we administered the MSCEIT together with measures of crystallized and fluid
      intelligence, personality, and affect. In Study 2, we administered the MSCEIT
      together with indexes of dispositional coping, emotion regulation strategies,
      alexithymia, state-trait anxiety, depression, and depressive rumination. We
      evaluated the factorial structure of the MSCEIT with a confirmatory factor
      analysis model using data combined from Study 1 and 2. The results confirm that
      the MSCEIT Italian version satisfactorily discriminates emotional intelligence
      ability from crystallized and fluid intelligence, personality, and affect, and
      exhibits significant correlations with various psychological well-being criteria.
      Furthermore, data from both studies confirm that the factorial structure of
      MSCEIT is consistent with the theory on which it is based, although it was
      difficult to rule out alternative structures. 

PMID- 23536992
TI  - Social and emotional processing in Prader-Willi syndrome: genetic subtype
      differences.
AB  - BACKGROUND: People with Prader-Willi syndrome (PWS) demonstrate social
      dysfunction and increased risk of autism spectrum disorder, especially those with
      the maternal uniparental disomy (mUPD) versus paternal deletion genetic subtype.
      This study compared the neural processing of social (faces) and nonsocial
      stimuli, varying in emotional valence, across genetic subtypes in 24 adolescents
      and adults with PWS. METHODS: Upright and inverted faces, and nonsocial objects
      with positive and negative emotional valence were presented to participants with
      PWS in an oddball paradigm with smiling faces serving as targets. Behavioral and
      event-related potential (ERP) data were recorded. RESULTS: There were no genetic
      subtype group differences in accuracy, and all participants performed above
      chance level. ERP responses revealed genetic subtype differences in face versus
      object processing. In those with deletions, the face-specific posterior N170
      response varied in size for face stimuli versus inverted faces versus nonsocial
      objects. Persons with mUPD generated N170 of smaller amplitude and showed no
      stimulus differentiation. Brain responses to emotional content did not vary by
      subtype. All participants elicited larger posterior and anterior late positive
      potential responses to positive objects than to negative objects. Emotion-related
      differences in response to faces were limited to inverted faces only in the form
      of larger anterior late positive potential amplitudes to negative emotions over
      the right hemisphere. Detection of the target smiling faces was evident in the
      increased amplitude of the frontal and central P3 responses but only for inverted
      smiling faces. CONCLUSION: Persons with the mUPD subtype of PWS may show atypical
      face versus object processes, yet both subtypes demonstrated potentially altered
      processing, attention to and/or recognition of faces and their expressions.

PMID- 23536993
TI  - Estimation of optic nerve sheath diameter on an initial brain computed tomography
      scan can contribute prognostic information in traumatic brain injury patients.
AB  - INTRODUCTION: The aim of this study was to evaluate the prognostic value of optic
      nerve sheath diameter (ONSD) measured on the initial brain computed tomography
      (CT) scan for intensive care unit (ICU) mortality in severe traumatic brain
      injury (TBI) patients. METHODS: A prospective observational study of all severe
      TBI patients admitted to a neurosurgical ICU (over a 10-month period).
      Demographic and clinical data and brain CT scan results were recorded. ONSD for
      each eye was measured on the initial CT scan. The group of ICU survivors was
      compared to non-survivors. Glasgow Outcome Scale (GOS) was evaluated six months
      after ICU discharge. RESULTS: Seventy-seven patients were included (age: 43+/-18;
      81% males; mean Injury Severity Score: 35+/-15; ICU mortality: 28.5% (n=22)).
      Mean ONSD on the initial brain CT scan was 7.8+/-0.1 mm in non-survivors vs.
      6.8+/-0.1 mm in survivors (P<0.001). The operative value of ONSD was a good
      predictor of mortality (area under the curve: 0.805). An ONSD cutoff>=7.3 had a
      sensitivity of 86.4% and a specificity of 74.6% and was independently associated
      with mortality in this population (adjusted odds ratio 95% confidence interval:
      22.7 (3.2 to 159.6), P=0.002). There was a relationship between initial ONSD
      values and six-month GOS (P=0.03). CONCLUSIONS: ONSD measured on the initial
      brain CT scan is independently associated with ICU mortality rate (when >=7.3 mm)
      in severe TBI patients.See related commentary by Masquere et
      al.,http://ccforum.com/content/17/3/151.

PMID- 23536994
TI  - Quantitative neurosensory findings, symptoms and signs in young vibration exposed
      workers.
AB  - BACKGROUND: Long-term exposure to hand-held vibrating tools may cause the hand
      arm vibration syndrome (HAVS) including vibration induced white fingers and
      sensorineural symptoms. The aim was to study early neurosensory effects by
      quantitative vibrotactile and monofilament tests in young workers with hand-held
      vibration exposure. METHODS: This cross-sectional study consisted of 142 young,
      male machine shop and construction workers with hand-held exposure to vibrating
      tools. They were compared with 41 non-vibration exposed subjects of the same age
      group. All participants passed a structured interview, answered several
      questionnaires and had a physical examination including the determination of
      vibrotactile perception thresholds (VPTs) at two frequencies (31.5 and 125 Hz)
      and Semmes Weinstein's Monofilament test. RESULTS: In the vibration exposed group
      8% of the workers reported episodes of tingling sensations and 10% numbness in
      their fingers. Approximately 5-10% of the exposed population displayed abnormal
      results on monofilament tests. The vibrotactile testing showed significantly
      increased VPTs for 125 Hz in dig II bilaterally (right hand, p = 0.01; left hand,
      p = 0.024) in the vibration exposed group.A multiple regression analysis (VPT -
      dependent variable; age, height, examiner and five different vibration dose
      calculations - predictor variables) in dig II bilaterally showed rather low R2
      values. None of the explanatory variables including five separately calculated
      vibration doses were included in the models, neither for the total vibration
      exposed group, nor for the highest exposed quartile.A logistic multiple
      regression analysis (result of monofilament testing - dependent variable; age,
      height, examiner and five vibration dose calculations - predictor variables) of
      the results of monofilament testing in dig II bilaterally gave a similar outcome.
      None of the independent variables including five calculated vibration doses were
      included in the models neither for the total exposed group nor for the highest
      exposed quartile. CONCLUSION: In spite of the fairly short vibration exposure, a
      tendency to raised VPTs as well as pathologic monofilament test results was
      observed. Thus, early neurophysiologic symptoms and signs of vibration exposure
      may appear after short-term exposure also in young workers.

PMID- 23536995
TI  - Demonstration of protein-fragment complementation assay using purified firefly
      luciferase fragments.
AB  - BACKGROUND: Human interactome is predicted to contain 150,000 to 300,000 protein
      protein interactions, (PPIs). Protein-fragment complementation assay (PCA) is one
      of the most widely used methods to detect PPI, as well as Forster resonance
      energy transfer (FRET). To date, successful applications of firefly luciferase
      (Fluc)-based PCA have been reported in vivo, in cultured cells and in cell-free
      lysate, owing to its high sensitivity, high signal-to-background (S/B) ratio, and
      reversible response. Here we show the assay also works with purified proteins
      with unexpectedly rapid kinetics. RESULTS: Split Fluc fragments both fused with a
      rapamycin-dependently interacting protein pair were made and expressed in E. coli
      system, and purified to homogeneity. When the proteins were used for PCA to
      detect rapamycin-dependent PPI, they enabled a rapid detection (~1 s) of PPI with
      high S/B ratio. When Fn7-8 domains (7 nm in length) that was shown to abrogate
      GFP mutant-based FRET was inserted between split Fluc and FKBP12 as a rigid
      linker, it still showed some response, suggesting less limitation in interacting
      partner's size. Finally, the stability of the probe was investigated.
      Preincubation of the probes at 37 degree C up to 1 h showed marked decrease of
      the luminescent signal to 1.5%, showing the limited stability of this system.
      CONCLUSION: Fluc PCA using purified components will enable a rapid and handy
      detection of PPIs with high S/B ratio, avoiding the effects of concomitant
      components. Although the system might not be suitable for large-scale screening
      due to its limited stability, it can detect an interaction over larger distance
      than by FRET. This would be the first demonstration of Fluc PCA in vitro, which
      has a distinct advantage over other PPI assays. Our system enables detection of
      direct PPIs without risk of perturbation by PPI mediators in the complex cellular
      milieu.

PMID- 23536996
TI  - Cytokine-induced killer cells promote antitumor immunity.
AB  - The number of immune cells, especially dendritic cells and cytotoxic tumor
      infiltrating lymphocytes (TIL), particularly Th1 cells, CD8 T cells, and NK cells
      is associated with increased survival of cancer patients. Such antitumor cellular
      immune responses can be greatly enhanced by adoptive transfer of activated type 1
      lymphocytes. Recently, adoptive cell therapy based on infusion of ex vivo
      expanded TILs has achieved substantial clinical success. Cytokine-induced killer
      (CIK) cells are a heterogeneous population of effector CD8 T cells with diverse
      TCR specificities, possessing non-MHC-restricted cytolytic activities against
      tumor cells. Preclinical studies of CIK cells in murine tumor models demonstrate
      significant antitumor effects against a number of hematopoietic and solid tumors.
      Clinical studies have confirmed benefit and safety of CIK cell-based therapy for
      patients with comparable malignancies. Enhancing the potency and specificity of
      CIK therapy via immunological and genetic engineering approaches and identifying
      robust biomarkers of response will significantly improve this therapy.

PMID- 23536997
TI  - The Qure study: Q fever fatigue syndrome--response to treatment; a randomized
      placebo-controlled trial.
AB  - BACKGROUND: Q fever is a zoonosis that is present in many countries. Q fever
      fatigue syndrome (QFS) is one of the most frequent sequelae after an acute Q
      fever infection. QFS is characterized by persistent fatigue following an acute Q
      fever infection, leading to substantial morbidity and a high socio-economic
      burden. The occurrence of QFS is well-documented, and has been described in many
      countries over the past decades. However, a treatment with proven efficacy is not
      available. Only a few uncontrolled studies have tested the efficacy of treatment
      with antibiotics on QFS. These studies suggest a positive effect of long-term
      treatment with a tetracycline on performance state; however, no randomized
      controlled trials have been performed. Cognitive behavioral therapy (CBT) has
      been proven to be an effective treatment modality for chronic fatigue in other
      diseases, but has not yet been tested in QFS. Therefore, we designed a trial to
      assess the efficacy of long-term treatment with the tetracycline doxycycline and
      CBT in patients with QFS. METHODS/DESIGN: A randomized placebo-controlled trial
      will be conducted. One-hundred-eighty adult patients diagnosed with QFS will be
      recruited and randomized between one of three groups: CBT, long-term doxycycline
      or placebo. First, participants will be randomized between CBT and medication
      (ratio 1:2). A second double-blinded randomization between doxycycline and
      placebo (ratio 1:1) will be performed in the medication condition. Each group
      will be treated for six months. Outcome measures will be assessed at baseline and
      post intervention. The primary outcome measure is fatigue severity. Secondary
      outcome measures are functional impairment, level of psychological distress, and
      Coxiella burnetii PCR and serology. DISCUSSION: The Qure study is the first
      randomized placebo-controlled trial, which evaluates the efficacy of long-term
      doxycycline and of cognitive behavioral therapy in patients with QFS. The results
      of this study will provide knowledge about evidence-based treatment options for
      adult patients with QFS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01318356, and
      Netherlands Trial Register: NTR2797.

PMID- 23536998
TI  - Profile of children admitted with seizures in a tertiary care hospital of Western
      Nepal.
AB  - BACKGROUND: Seizure is one of the common causes of childhood hospitalization with
      significant mortality and morbidity. There is limited data regarding acute
      seizures episodes form the developing countries. Current study aims to find the
      common etiology of seizure and classify seizure types in various age groups
      presenting to tertiary center in Western Nepal. METHODS: This was a hospital
      based retrospective study carried out in the data retrieved from the records
      maintained in the Department of Pediatrics, Manipal Teaching Hospital, Pokhara
      from 1st July 2007 to 31st July 2011.Variables collected were demographics,
      clinical presentations, laboratory tests, brain imaging studies,
      electroencephalography, diagnosis and hospital course. RESULTS: A total of 551
      patients were admitted for seizures with 338 (61.3%) males and 213 (38.7%)
      females. Among these patients, 295 (53.5%) presented with fever and 317 (57.5%)
      of children were less than 5 years of age. Generalized tonic-clonic seizures were
      the most common seizure type (69.9%). Seizure disorder (33.4%), febrile seizures
      (30.7%), CNS infections and neurocysticercosis were common etiologies. Abnormal
      brain images were noted in 111 (45.9%) of 242 patients and most common
      abnormality was neurocysticercosis 66 (59.5%). CONCLUSION: CNS infections and
      febrile convulsions were common causes of seizures in febrile children.
      Neuroimaging should be advised in all afebrile children for the diagnosis of
      neurocysticercosis. Children diagnosed as seizure disorder require long term
      follow up studies including neurophysiologic studies.

PMID- 23536999
TI  - Sagittal abdominal diameter is a more independent measure compared with waist
      circumference to predict arterial stiffness in subjects with type 2 diabetes--a
      prospective observational cohort study.
AB  - BACKGROUND: Anthropometric measurements are useful in clinical practice since
      they are non-invasive and cheap. Previous studies suggest that sagittal abdominal
      diameter (SAD) may be a better measure of visceral fat depots. The aim of this
      study was to prospectively explore and compare how laboratory and anthropometric
      risk markers predicted subclinical organ damage in 255 patients, with type 2
      diabetes, after four years. METHODS: Baseline investigations were performed in
      2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT)
      was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was
      measured with applanation tonometry over the carotid and femoral arteries at
      baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55-65
      years old. RESULTS: There were significant correlations between apolipoprotein B
      (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009)
      at baseline and IMT measured at follow-up. After adjustment for sex, age,
      treatment with statins and Hba1c, the associations remained statistically
      significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT
      at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist
      circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD)
      (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP
      and HbA1c, the association between SAD, not WC nor BMI, and PWV remained
      statistically significant (p = 0.036). In a stepwise linear regression, entering
      both SAD and WC, the association between SAD and PWV was stronger than the
      association between WC and PWV. CONCLUSIONS: We conclude that apoB and CRP, but
      not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was
      more independent in predicting arterial stiffness over time, compared with WC, in
      middle-aged men and women with type 2 diabetes.

PMID- 23537000
TI  - Chemo-sensors development based on low-dimensional codoped Mn2O3-ZnO
      nanoparticles using flat-silver electrodes.
AB  - BACKGROUND: Semiconductor doped nanostructure materials have attained
      considerable attention owing to their electronic, opto-electronic, para-magnetic,
      photo-catalysis, electro-chemical, mechanical behaviors and their potential
      applications in different research areas. Doped nanomaterials might be a
      promising owing to their high-specific surface-area, low-resistances, high
      catalytic activity, attractive electro-chemical and optical properties.
      Nanomaterials are also scientifically significant transition metal-doped
      nanostructure materials owing to their extraordinary mechanical, optical,
      electrical, electronic, thermal, and magnetic characteristics. Recently, it has
      gained significant interest in manganese oxide doped-semiconductor materials in
      order to develop their physico-chemical behaviors and extend their efficient
      applications. It has not only investigated the basic of magnetism, but also has
      huge potential in scientific features such as magnetic materials, bio- & chemi
      sensors, photo-catalysts, and absorbent nanomaterials. RESULTS: The chemical
      sensor also displays the higher-sensitivity, reproducibility, long-term
      stability, and enhanced electrochemical responses. The calibration plot is linear
      (r2 = 0.977) over the 0.1 nM to 50.0 MUM 4-nitrophenol concentration ranges. The
      sensitivity and detection limit is ~4.6667 MUA cm-2 MUM-1 and ~0.83 +/- 0.2 nM
      (at a Signal-to-Noise-Ratio, SNR of 3) respectively. To best of our knowledge,
      this is the first report for detection of 4-nitrophenol chemical with doped Mn2O3
      ZnO NPs using easy and reliable I-V technique in short response time.
      CONCLUSIONS: As for the doped nanostructures, NPs are introduced a route to a new
      generation of toxic chemo-sensors, but a premeditate effort has to be applied for
      doped Mn2O3-ZnO NPs to be taken comprehensively for large-scale applications, and
      to achieve higher-potential density with accessible to individual chemo-sensors.
      In this report, it is also discussed the prospective utilization of Mn2O3-ZnO NPs
      on the basis of carcinogenic chemical sensing, which could also be applied for
      the detection of hazardous chemicals in ecological, environmental, and health
      care fields.

PMID- 23537003
TI  - Patient reported determinants of health: a qualitative analysis of veterans with
      chronic obstructive pulmonary disease.
AB  - Although COPD is a common disorder of veterans who receive care from the Veterans
      Healthcare Administration (VHA), the perceptions of veterans with COPD about
      their disease, its effects on their lives, and their interactions with the VHA
      have not been determined. Utilizing qualitative methodology, we conducted focus
      groups of veterans with COPD at the Cincinnati VA Medical Center. Participants
      were selected by systematic sampling from the top quintile of veterans stratified
      by the cost of healthcare utilization related to a primary diagnosis of COPD and
      grouped by age and use of supplemental oxygen. All 42 participants were male and
      had a mean age of 65 years. Analysis of the focus group transcripts demonstrated
      five major themes: 1) Physical and Functional Limitations: work and employment
      constraints, recreation restrictions, limits on activities of daily living,
      reduced sexuality, concerns about housing and finances, and physical symptoms; 2)
      Restricted Social Interactions/Altered Social Networks: altered relationships
      with friends and family and reliance upon family and care givers; 3) Emotional
      Effects: reduced self-worth, vulnerability, depression, perseverance and
      adaptation, hopelessness, fear, pride, and lack of control; 4) Limitations in the
      Understanding of COPD: unawareness of diagnosis, triggers and reaction to disease
      manifestations, COPD management; and 5) Complex Healthcare Interactions. COPD
      pervasively and extensively affects all aspects of veterans' lives and causes
      significant consequences for their care and management.

PMID- 23537002
TI  - Prediction of constitutive A-to-I editing sites from human transcriptomes in the
      absence of genomic sequences.
AB  - BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is recognized as a cellular
      mechanism for generating both RNA and protein diversity. Inosine base pairs with
      cytidine during reverse transcription and therefore appears as guanosine during
      sequencing of cDNA. Current approaches of RNA editing identification largely
      depend on the comparison between transcriptomes and genomic DNA (gDNA) sequencing
      datasets from the same individuals, and it has been challenging to identify
      editing candidates from transcriptomes in the absence of gDNA information.
      RESULTS: We have developed a new strategy to accurately predict constitutive RNA
      editing sites from publicly available human RNA-seq datasets in the absence of
      relevant genomic sequences. Our approach establishes new parameters to increase
      the ability to map mismatches and to minimize sequencing/mapping errors and
      unreported genome variations. We identified 695 novel constitutive A-to-I editing
      sites that appear in clusters (named "editing boxes") in multiple samples and
      which exhibit spatial and dynamic regulation across human tissues. Some of these
      editing boxes are enriched in non-repetitive regions lacking inverted repeat
      structures and contain an extremely high conversion frequency of As to Is. We
      validated a number of editing boxes in multiple human cell lines and confirmed
      that ADAR1 is responsible for the observed promiscuous editing events in non
      repetitive regions, further expanding our knowledge of the catalytic substrate of
      A-to-I RNA editing by ADAR enzymes. CONCLUSIONS: The approach we present here
      provides a novel way of identifying A-to-I RNA editing events by analyzing only
      RNA-seq datasets. This method has allowed us to gain new insights into RNA
      editing and should also aid in the identification of more constitutive A-to-I
      editing sites from additional transcriptomes.

PMID- 23537001
TI  - Calcium-deficiency assessment and biomarker identification by an integrated
      urinary metabonomics analysis.
AB  - BACKGROUND: Calcium deficiency is a global public-health problem. Although the
      initial stage of calcium deficiency can lead to metabolic alterations or
      potential pathological changes, calcium deficiency is difficult to diagnose
      accurately. Moreover, the details of the molecular mechanism of calcium
      deficiency remain somewhat elusive. To accurately assess and provide appropriate
      nutritional intervention, we carried out a global analysis of metabolic
      alterations in response to calcium deficiency. METHODS: The metabolic alterations
      associated with calcium deficiency were first investigated in a rat model, using
      urinary metabonomics based on ultra-performance liquid chromatography coupled
      with quadrupole time-of-flight tandem mass spectrometry and multivariate
      statistical analysis. Correlations between dietary calcium intake and the
      biomarkers identified from the rat model were further analyzed to confirm the
      potential application of these biomarkers in humans. RESULTS: Urinary metabolic
      profiling analysis could preliminarily distinguish between calcium-deficient and
      non-deficient rats after a 2-week low-calcium diet. We established an integrated
      metabonomics strategy for identifying reliable biomarkers of calcium deficiency
      using a time-course analysis of discriminating metabolites in a low-calcium diet
      experiment, repeating the low-calcium diet experiment and performing a calcium
      supplement experiment. In total, 27 biomarkers were identified, including
      glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine,
      indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary
      metabonomics analysis, which combined biomarkers with regular trends of change
      (types A, B, and C), could accurately assess calcium-deficient rats at different
      stages and clarify the dynamic pathophysiological changes and molecular mechanism
      of calcium deficiency in detail. Significant correlations between calcium intake
      and two biomarkers, pseudouridine (Pearson correlation, r = 0.53, P = 0.0001) and
      citrate (Pearson correlation, r = -0.43, P = 0.001), were further confirmed in 70
      women. CONCLUSIONS: To our knowledge, this is the first report of reliable
      biomarkers of calcium deficiency, which were identified using an integrated
      strategy. The identified biomarkers give new insights into the pathophysiological
      changes and molecular mechanisms of calcium deficiency. The correlations between
      calcium intake and two of the biomarkers provide a rationale or potential for
      further assessment and elucidation of the metabolic responses of calcium
      deficiency in humans.

PMID- 23537004
TI  - Electrospun nanofibers as substrates for surface-assisted laser
      desorption/ionization and matrix-enhanced surface-assisted laser
      desorption/ionization mass spectrometry.
AB  - Electrospun polymeric nanofibers (polyacrylonitrile, poly(vinyl alcohol), and SU
      8 photoresist) and carbon nanofibers pyrolyzed to final temperatures of 600, 800,
      and 900  degrees C were used as substrates for surface-assisted laser
      desorption/ionization (SALDI) and matrix-enhanced surface-assisted laser
      desorption/ionization (ME-SALDI) analyses. Sample preparation of polymeric
      analytes using the electrospun target plate for SALDI analysis is simple and
      fast. Signal enhancements for poly(ethylene glycol) were noted with nanofibrous
      carbon substrates compared to those obtained with commercially available
      stainless steel plates when no organic matrix is used. Minimal fragmentation was
      observed. Poly(ethylene glycol) with a molecular weight as high as 900 000 Da was
      successfully detected using the carbon nanofibrous substrate processed to 800 
      degrees C, which is the highest molecular weight that has been studied by SALDI.
      Small molecules were detected using nanofibrous carbon substrate processed to 800
      degrees C. For example, spectra of glucose, arginine, and crystal violet were
      obtained with no observed interferences in the low molecular weight range. The
      SALDI results show enhanced shot-to-shot reproducibility compared to matrix
      assisted laser desorption/ionization (MALDI). High-quality polystyrene spectra
      were obtained for the first time using SALDI nanofibrous polyacrylonitrile
      substrates. Significantly enhanced signal-to-noise ratios were obtained using ME
      SALDI compared to conventional MALDI or SALDI for the studied analytes. A
      detection limit of 400 amol was achieved for angiotensin I using the nanofibrous
      carbon ME-SALDI substrate. 

PMID- 23537005
TI  - Biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) by human liver
      microsomes: identification of cytochrome P450 2B6 as the major enzyme involved.
AB  - Polybrominated diphenyl ethers (PBDEs) were widely used flame retardants that
      have become persistent environmental pollutants. In the present study, we
      investigated the in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl
      ether (BDE-47), a major PBDE detected in human tissue and environmental samples.
      Biotransformation of BDE-47 by pooled and individual human liver microsomes and
      by human recombinant cytochrome P450 (P450) enzymes was assessed using a liquid
      chromatography/tandem mass spectrometry-based method. Of the nine hydroxylated
      metabolites of BDE-47 produced by human liver microsomes, seven metabolites were
      identified using authentic standards. A monohydroxy-tetrabrominated and a
      dihydroxy-tetrabrominated metabolite remain unidentified. Kinetic analysis of the
      rates of metabolite formation revealed that the major metabolites were 5-hydroxy
      2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE-47), 6-hydroxy-2,2',4,4'
      tetrabromodiphenyl ether (6-OH-BDE-47), and possibly the unidentified monohydroxy
      tetrabrominated metabolite. Among the human recombinant P450 enzymes tested, P450
      2B6 was the most active enzyme in the formation of the hydroxylated metabolites
      of BDE-47. Moreover, the formation of all metabolites of BDE-47 by pooled human
      liver microsomes was inhibited by a P450 2B6-specific antibody and was highly
      correlated with P450 2B6-mediated activity in single donor liver microsomes
      indicating that P450 2B6 was the major P450 responsible for the biotransformation
      of BDE-47. Additional experiments involving the incubation of liver microsomes
      with individual monohydroxy-tetrabrominated metabolites in place of BDE-47
      demonstrated that 2,4-dibromophenol was a product of BDE-47 and several primary
      metabolites, but the dihydroxy-tetrabrominated metabolite was not formed by
      sequential hydroxylation of any of the monohydroxy-tetrabrominated metabolites
      tested. The present study provides a comprehensive characterization of the
      oxidative metabolism of BDE-47 by human liver microsomes and P450 2B6.

PMID- 23537006
TI  - Molecular assessment of apicomplexan parasites in the snake Psammophis from North
      Africa: do multiple parasite lineages reflect the final vertebrate host diet?
AB  - The Apicomplexa are intracellular pathogens of animals, with the Coccidia being
      the largest group. Among these are the hemogregarines, which include some of the
      most common hemoparasites found in reptiles. Several studies have reported a
      possible pattern of prey-predator transmission for some of these parasites.
      Snakes from the Mediterranean region have been found to be parasitized with
      Hepatozoon spp. similar to those in lacertids and gekkonids, supporting the prey
      predator transmission hypothesis. Here we analyzed specimens of the saurophagous
      genus Psammophis from North Africa, an ecologically different region. Through
      molecular analysis of tissue samples we detected 3 different apicomplexan
      parasites: Caryospora, Sarcocystis, and Hepatozoon. Caryospora was detected in a
      Forskal's sand snake Psammophis schokari from Algeria, constituting the first
      time these parasites have been detected from a tissue sample through molecular
      screening. The obtained Sarcocystis phylogeny does not reflect the relationships
      of their final hosts, with the parasites identified from snakes forming at least
      3 unrelated groups, indicating that it is still premature to predict definitive
      host based on the phylogeny of these parasites. Three unrelated lineages of
      Hepatozoon parasites were identified in Psammophis, each closely related to
      lineages previously identified from different lizard groups, on which these
      snakes feed. This once again indicates that diet might be a key element in
      transmission, at least for Hepatozoon species of saurophagous snakes.

PMID- 23537007
TI  - On the symmetry and degeneracy of H3(+).
AB  - The fundamental molecular ion H3(+) has impacted astronomy, chemistry, and
      physics, particularly since the discovery of its rovibrational spectrum.
      Consisting of three identical fermions, its properties are profoundly influenced
      by the requirements of exchange symmetry, most notably the nonexistence of its
      ground rotational state. Spectroscopy of H3(+) is often used to infer the
      relative abundances of its two nuclear spin modifications, ortho- and para-H3(+),
      which are important in areas as diverse as electron dissociative recombination
      and deuterium fractionation in cold interstellar clouds. In this paper, we
      explore in detail the impact of exchange symmetry on the states of H3(+), with a
      particular focus on the state degeneracies necessary for converting spectral
      transition intensities to relative abundances. We address points of confusion in
      the literature surrounding these issues and discuss the implications for proton
      transfer reactions of H3(+) at low temperatures.

PMID- 23537008
TI  - The effect of high-intensity focused ultrasound treatment on immune function in
      patients with uterine fibroids.
AB  - PURPOSE: The aim of this study was to investigate the effect of high-intensity
      focused ultrasound (HIFU) on immune function in patients with uterine fibroids,
      in a randomised comparison to conventional myomectomy. METHODS: The patients were
      assigned (1:1) to the HIFU group or the myomectomy (MY) group. Venous blood
      samples were collected 24 h before and 24 h and 72 h after operation. The
      percentages of CD4(+) and CD8(+) T cells and natural killer (NK) cells were
      quantified by flow cytometry (FCM). Serum levels of interleukin-2 (IL-2), IL-6
      and IL-10 were determined using enzyme-linked immunosorbent assay. RESULTS: HIFU
      was associated with early ambulation, fewer post-operative complications, and
      shorter hospital stay (p < 0.001). The percentages of CD4(+) and CD8(+) T cells
      and NK cells in the HIFU group were not significantly altered after treatment
      compared with before treatment. In contrast, the numbers of these cells in the MY
      group decreased significantly 24 h after conventional myomectomy (p < 0.001). The
      CD4(+)/CD8(+) T cell ratios were also decreased significantly 24 h and 72 h after
      conventional myomectomy (p < 0.001). Serum levels of IL-6 and IL-10 increased
      after treatment in both groups. Peak IL-6 and IL-10 levels were significantly
      lower in the HIFU group than in the MY group (p < 0.001). In contrast, IL-2 level
      decreased significantly in the MY group compared to the HIFU group at 24 h post
      operation (p < 0.001). CONCLUSIONS: Short-term post-operative immune function is
      better preserved after HIFU treatment. Better preserved immune function may
      reflect a reduction in tissue trauma after HIFU treatment and contribute to
      reduced post-operative complications.

PMID- 23537009
TI  - Does self-complexity moderate the effects of exposure to political violence for
      adolescents?
AB  - This study examined the moderating role of self-complexity (SC) on well-being
      (WB) and psychopathology among Israeli adolescents exposed to the Second Lebanon
      War (2006). Adolescents (N=584, mean age 16.41) completed a SC measure, Political
      and Negative Life Events (NLE) scales, Brief Symptom Inventory and Satisfaction
      with Life Scale. The theoretical model analyzed the function of SC as a moderator
      of exposure effects to political life events (PLE), while controlling for general
      NLE. Results corroborated the model with SC moderating the effects of the war
      related PLE. Adolescents with low SC are at risk for damaged WB and psychiatric
      consequences from political violence exposure. This opens a diagnostic avenue for
      identification of at-risk adolescents in this socio-political context toward whom
      clinical programs should be directed. 

PMID- 23537010
TI  - Composite MOF foams: the example of UiO-66/polyurethane.
AB  - Composite MOF foams were prepared using a direct synthesis of UiO-66 over a
      polyurethane foam template. Under optimized conditions, the composite materials
      maintained the macrostructure and flexibility of the polyurethane foam, and
      exhibited the microporosity, high surface area, and adsorption properties of the
      UiO-66. The composite MOF foam has hierarchical porosity and high adsorption
      capacity for benzene and n-hexane, maintaining more than 70% of the adsorption
      capacity of the UiO-66.

PMID- 23537011
TI  - Lewis acid enhanced axial ligation of [Mo2]4+ complexes.
AB  - We report here the syntheses, X-ray crystal structures, electrochemistry, and
      density functional theory (DFT) single-point calculations of three new complexes:
      tetrakis(monothiosuccinimidato)dimolybdenum(II) [Mo2(SNO5)4, 1a], tetrakis(6
      thioxo-2-piperidinonato)dimolybdenum(II) [Mo2(SNO6)4, 1b], and
      chlorotetrakis(monothiosuccinimidato)pyridinelithiumdimolybdenum(II)
      [pyLiMo2(SNO5)4Cl, 2-py]. X-ray crystallography shows unusually short axial Mo2
      Cl bond lengths in 2-py, 2.6533(6) A, and dimeric 2-dim, 2.644(1) A, which we
      propose result from an increased Lewis acidity of the Mo2 unit in the presence of
      the proximal Li(+) ion. When 2-py is dissolved in MeCN, the lithium reversibly
      dissociates, forming an equilibrium mixture of (MeCNLiMo2(SNO5)4Cl) (2-MeCN) and
      [Li(MeCN)4](+)[Mo2(SNO5)4Cl](-) (3). Cyclic voltammetry was used to determine the
      equilibrium lithium binding constant (room temperature, K(eq) = 95 +/- 1). From
      analysis of the temperature dependence of the equilibrium constant, thermodynamic
      parameters for the formation of 2-MeCN from 3 (DeltaH degrees  = -6.96 +/- 0.93
      kJ mol(-1) and DeltaS degrees  = 13.9 +/- 3.5 J mol(-1) K(-1)) were extracted.
      DFT calculations indicate that Li(+) affects the Mo-Cl bond length through
      polarization of metal-metal bonding/antibonding molecular orbitals when lithium
      and chloride are added to the dimolybdenum core.

PMID- 23537012
TI  - Effects of ambient temperature on mechanomyography of resting quadriceps muscle.
AB  - It has been speculated that resting muscle mechanical activity, also known as
      minor tremor, microvibration, and thermoregulatory tonus, has evolved to maintain
      core temperature in homeotherms, and may play a role in nonshivering
      thermogenesis. This experiment was done to determine whether resting muscle
      mechanical activity increases with decreasing ambient temperature. We cooled 20
      healthy, human, resting, supine subjects from an ambient temperature of 40
      degrees  to 12  degrees C over 65 min. Core temperature, midquadriceps
      mechanomyography, surface electromyography, and oxygen consumption (VO2) were
      recorded. Resting muscle mechanical and electrical activity in the absence of
      shivering increased significantly at temperatures below 21.5  degrees C. Women
      defended core temperature more effectively than men, and showed increased resting
      muscle activity earlier than men. Metabolism measured by VO2 correlated with
      resting muscle mechanical activity (R = 0.65; p = 0.01). Resting muscle
      mechanical activity may have evolved, in part, to maintain core temperature in
      the face of mild cooling.

PMID- 23537013
TI  - Do Canadians meet Canada's Food Guide's recommendations for fruits and
      vegetables?
AB  - National dietary guidelines pertaining to the intake of fruits and vegetables
      (FV) were recently amended, in both Canada and the United States, to provide
      specific recommendations about dark green and orange vegetables and juice
      consumption. However, little is known about the extent to which Canadians meet
      the updated recommendations for FV. This study fills current gaps by applying the
      National Cancer Institute's methodology for assessing the distribution of usual
      intake of foods to examine reported FV intake using 24-h recalls from the 2004
      Canadian Community Health Survey, cycle 2.2, a nationally representative health
      survey. After identifying plausible respondents, usual intake distributions were
      estimated after adjustment for respondents' age, sex, body mass index, frequency
      of FV consumption, sequence effect, weekend-weekday effect, income, and
      ethnicity. The majority of Canadians did not meet Health Canada's 2007
      recommendations for FV intake. Only 26% of the population aged 2 years and older
      consumed the minimum number of daily servings recommended for their respective
      age-sex group. Approximately 1 in 5 Canadians consumed at least 1 daily serving
      of dark green vegetables, and 9% consumed 1 or more daily servings of orange
      vegetables or their substitutes. Juice was a substantial contributor to FV
      intake, particularly for children and teens who, on average, consumed 32%-41% of
      their daily FV servings as juice. These findings provide insight into the
      quantity and composition of FV intake and adherence to national dietary
      recommendations in Canada.

PMID- 23537014
TI  - Association between plasma omega-3 fatty acids and cardiovascular disease risk
      factors.
AB  - The consumption of omega-3 (n-3) fatty acids (FA), namely eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA), have been linked to reduced cardiovascular
      disease (CVD) risk. The objective of this study was to examine the relation
      between n-3 FA in plasma phospholipid (PL) levels and CVD risk factors. n-3 FA
      levels in plasma PL were determined using gas chromatography in 100 obese (body
      mass index (BMI), >=30 kg.m(-2)) and 100 nonobese selected individuals from the
      Quebec City metropolitan area. The CVD risk factors analysed were BMI, blood
      pressure, plasma lipids levels, and fasting plasma glucose. Significantly higher
      levels of alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) were
      observed in obese subjects, whereas significantly higher levels of DHA were
      observed in nonobese subjects. For CVD risk factors, ALA levels were positively
      correlated with plasma triglyceride concentrations and negatively associated with
      diastolic blood pressure. None of the CVD risk factors studied was linked to EPA
      levels. In addition, DPA was negatively related to high-density lipoprotein
      cholesterol (HDL-C) and positively correlated with the total cholesterol/HDL-C
      ratio. DHA levels were negatively correlated with BMI, waist circumference, and
      plasma triglyceride levels, whereas a positive association was observed with HDL
      C levels. Total n-3 FA percentages were negatively correlated with BMI. In
      conclusion, higher DHA percentages in plasma PL are associated with a more
      favourable CVD risk profile, whereas higher DPA percentages in plasma PL are
      associated with a more deteriorated CVD risk profile.

PMID- 23537015
TI  - Top 10 practical lessons learned from physical activity interventions in
      overweight and obese children and adolescents.
AB  - Physical activity (PA) interventions targeting overweight and obese children and
      adolescents have shown only modest success, and dropout is an area of concern.
      Proper design and implementation of a PA intervention is critical for maximizing
      adherence and thus increasing the overall health benefits from PA participation.
      We propose practical advice based on our collective clinical trial experience
      with support from the literature on best practices related to PA interventions in
      overweight and obese children and adolescents. The top 10 lessons learned are (i)
      PA setting-context is important; (ii) choice of fitness trainer matters; (iii)
      physical activities should be varied and fun; (iv) the role of the parent
      guardian should be considered; (v) individual physical and psychosocial
      characteristics should be accounted for; (vi) realistic goals should be set;
      (vii) regular reminders should be offered; (viii) a multidisciplinary approach
      should be taken; (ix) barriers should be identified early and a plan to overcome
      them developed; and (x) the right message should be communicated: specifically,
      what's in it for them? The recommendations in this paper can be used in other
      pediatric PA programs, physical education settings, and public health programs,
      with the hope of decreasing attrition and increasing the benefits of PA
      participation to promote health in children and adolescents.

PMID- 23537016
TI  - Grape seed and skin extract alleviates high-fat diet-induced renal lipotoxicity
      and prevents copper depletion in rat.
AB  - Obesity is a public health problem that contributes to morbidity and mortality
      from diabetes, heart disease, stroke, and cancers. The purpose of this
      investigation was to analyse the link between obesity-induced oxidative stress,
      renal steatosis, and kidney dysfunction, as well as the protective effect of
      grape seed and skin extract. Rats were fed a standard diet or a high-fat diet for
      6 weeks and were either treated or not treated with grape seed and skin extract.
      Fat-induced oxidative stress was evaluated in the kidney with a special emphasis
      on transition metals. High-fat diet induced triglyceride deposition and
      disturbances in kidney function parameters, which are linked to an oxidative
      stress status and depletion of copper from the kidney. Grape seed and skin
      extract abrogated almost all fat-induced kidney disturbances. Grape seed and skin
      extract exerted potential protection against fat-induced kidney lipotoxicity and
      should find potential application in other kidney-related diseases.

PMID- 23537017
TI  - Vitamin C prevents the acute decline of flow-mediated dilation after altered
      shear rate patterns.
AB  - Oscillatory and retrograde shear rate (SR) impairs endothelial function,
      potentially through shear-induced oxidative stress. We tested the hypothesis that
      acute vitamin C supplementation would prevent the attenuation of brachial artery
      flow-mediated dilation (FMD) after a period of augmented oscillatory and
      retrograde SR. Twelve healthy men (aged 26 +/- 3 years) participated in two 30
      min study visits in which one arm was subjected to increased oscillatory and
      retrograde SR, using 60 mm Hg of forearm cuff compression, and the contralateral
      arm served as the control. Subjects ingested capsules containing either placebo
      (sucrose) or vitamin C at 90 and 120 min (1000 mg total vitamin C) prior to cuff
      compression periods in a randomized placebo-controlled double-blind crossover
      study. Oscillatory and retrograde SR in the cuffed arms increased during the
      compression periods in the placebo and vitamin C study visits (p < 0.01 for
      both), with no difference between studies (p > 0.05). Antegrade SR remained
      unchanged throughout the compression periods (p > 0.05), and mean SR was lower in
      the cuffed arm than in the control arm for both study visits (p < 0.05). FMD
      decreased after cuff compression in the placebo cuffed arm (precompression vs.
      postcompression, 5.2% +/- 1.4% vs. 3.5% +/- 1.4%; p < 0.05), but remained
      unchanged after vitamin C therapy in the cuffed arm (precompression vs.
      postcompression, 5.3% +/- 2.4% vs. 5.7% +/- 2.6%; p > 0.05). No FMD changes were
      observed in the control arm for either study visit (p > 0.05). These data
      demonstrate that acute vitamin C supplementation prevents the attenuation of FMD
      due to altered SR patterns, suggesting that oxidative stress contributes to the
      oscillatory and retrograde SR-induced impairment of FMD.

PMID- 23537018
TI  - Protective effect of grape seed extracts on human lymphocytes: a preliminary
      study.
AB  - Grape seed extracts (GSEs) possess a broad spectrum of antioxidative properties
      that protects various cells from free radicals and oxidative stress. In this
      study, the genoprotective effect of GSE on human lymphocytic DNA was studied
      using standard and lysed cell comet assays. Lymphocytes from 5 healthy subjects
      were pretreated with GSE in different concentrations. The standard and lysed cell
      comet assays were performed on treated, untreated, challenged, and unchallenged
      cells in parallel. Cells were then subjected to an oxidant challenge induced with
      5-min exposures to hydrogen peroxide. In the standard comet assay, GSE
      significantly diminished hydrogen-peroxide-induced DNA damage in a dose-dependent
      manner. In the lysed cell assay, however, the antioxidant effect was diminished
      at a higher GSE concentration. Data indicate that the cell membrane might play a
      role in limiting cellular access to antioxidants, which directly affects the
      genoprotective or potential pro-oxidant effect of antioxidants on human DNA.
      Using both standard and lysed cell comet assays in parallel could be a useful way
      to elucidate the mechanism of protection or damage by antioxidants.

PMID- 23537019
TI  - Lower leptin levels are associated with higher risk of weight gain over 2 years
      in healthy young adults.
AB  - Complete leptin deficiency is associated with weight gain and extreme obesity,
      according to studies of animals and of monogenic obesity in humans. It is still a
      matter of debate whether relative leptin deficiency plays a physiologic role in
      adiposity regulation in free-living humans. We hypothesized that leptin levels
      would be associated with subsequent weight changes in healthy normal-weight young
      adults. Our prospective cohort involved 150 healthy young adults (114 women and
      36 men) followed over their years of study at the Universite de Sherbrooke.
      Anthropometric measurements, fasting blood samples, 3-day food diaries, and a
      physical activity questionnaire were collected at baseline. Leptin levels were
      measured with radioimmunoassay. Associations between baseline leptin levels and
      subsequent anthropometric changes were assessed with multivariable linear
      regression models to account for adiposity at baseline, food intake, and energy
      expenditure. Over the 2-year follow-up, changes in body mass index (BMI) ranged
      from -0.8 to +2.6 kg.m(-2) in men (mean BMI change, +0.6 kg.m(-2)) and from -2.5
      to +3.7 kg.m(-2) in women (mean BMI change, +0.1 kg.m(-2)). Lower leptin levels
      at baseline were associated with a higher risk of weight gain in women (r = 
      0.24; p = 0.01 for change in BMI) and in men (r = -0.27, p = 0.11), even after
      accounting for baseline BMI, total daily caloric intake, and energy expenditure
      (p = 0.02). In the subsample measured at 4 years (n = 63), baseline leptin levels
      were not associated with 4-year weight changes. Lower leptin levels are
      associated with a higher risk of weight gain over 2 years in healthy young
      adults.

PMID- 23537020
TI  - Influence of body mass loss and myoglobinuria on the development of muscle
      fatigue after a marathon in a warm environment.
AB  - The aim of this study was to determine the changes in body mass and myoglobinuria
      concentration in recreational runners during a marathon in a warm environment,
      and the relation of these changes to muscle fatigue. We recruited 138 amateur
      runners (114 men and 24 women) for the study. Before the race, leg muscle power
      output was measured during a countermovement jump on a force platform, body
      weight was measured, and a urine sample was obtained. Within 3 min of race
      completion (28  degrees C; 46% relative humidity), the runners repeated the
      countermovement jump, body weight was measured again, and a second urine sample
      was obtained. Myoglobin concentration was determined in the urine samples. After
      the race, mean body mass reduction was 2.2% +/- 1.2%. Fifty-five runners (40% of
      the total) reduced their body mass by less than 2%, and 10 runners (7.2%) reduced
      their body mass by more than 4%. Only 3 runners increased their body mass after
      the marathon. Mean leg muscle power reduction was 16% +/- 10%. Twenty-four
      runners reduced their muscle power by over 30%. No myoglobin was detected in the
      prerace urine specimens, whereas postrace urinary myoglobin concentration
      increased to 3.5 +/- 9.5 MUg.mL(-1) (p < 0.05). Muscle power change after the
      marathon significantly correlated with postrace urine myoglobin concentration (r
      = -0.55; p < 0.001), but not with body mass change (r = -0.08; p = 0.35). After a
      marathon in a warm environment, interindividual variability in body mass change
      was high, but only 7% of the runners reduced their body mass by more than 4%. The
      correlation between myoglobinuria and muscle power change suggests that muscle
      fatigue is associated with muscle breakdown.

PMID- 23537021
TI  - Firefighters muscular recovery after a heavy work bout in the heat.
AB  - Occasionally firefighters need to perform very heavy bouts of work, such as smoke
      diving or clearing an accident site, which induce significant muscle fatigue. The
      time span for muscular recovery from such heavy work is not known. The purpose of
      this study was to evaluate firefighters' force-, neural-, metabolic-, and
      structural-related recovery after task-specific heavy work in the heat. Fifteen
      healthy firefighters (14 males and 1 female) performed a 20-min heavy work bout
      that simulated smoke diving and the clearance of an accident site at 35  degrees
      C. After the work, muscular recovery was evaluated by wrist flexion maximal
      voluntary contraction (MVC), average electromyography during MVC and during
      10%MVC, rate of force production, motor response and stretch reflex responses,
      muscle oxygen consumption and oxygenation level, and wrist flexor muscle
      pennation angle. Recovery was followed for 4 h. Each of the 12 measured
      parameters changed significantly (p < 0.05) from those at baseline during the
      follow-up. Muscle oxygen consumption and the wrist flexor pennation angle
      remained elevated throughout the follow-up (oxygen consumption baseline, 12.9 +/-
      1.7 mL O2.min(-1).(100 g)(-1); 4-h value, 17.5 +/- 1.6 mL O2.min(-1).(100 g)(-1);
      p < 0.05 and pennation angle baseline, 15.7 +/- 0.8 degrees ; 4-h value, 17.8 +/-
      0.8 degrees ; p < 0.05). Muscle reoxygenation rate was elevated for up to 2 h
      (baseline, 2.3 +/- 0.4 MUmol.L(-1).min(-1); 2-h value, 3.4 +/- 0.4 MUmol.L(
      1).min(-1); p < 0.05). The other 9 parameters recovered (were no longer
      significantly different from baseline) after 20 to 60 min. We concluded that the
      recovery order in main components of muscle function from fastest to slowest was
      force, neural, metabolic, and structural.

PMID- 23537022
TI  - How is nutrition transition affecting dietary adequacy in Eeyouch (Cree) adults
      of Northern Quebec, Canada?
AB  - Rapid development, including the building of hydroelectric projects and roads in
      remote areas of Northern Quebec, Canada, has led to concerns about the
      contamination of traditional foods (TF) and a transition to a diet characterized
      by increased commercial food intake. A cross-sectional study of 850 Cree adults,
      aged >=19 years, from 7 of the 9 Eeyouch communities was conducted during the
      spring and summer seasons of 2005-2008. Anthropometric measures were collected.
      TF and dietary intake were assessed using food-frequency questionnaires (FFQs)
      and 24-h recalls. Obesity was high, with 77% of the women and 64% of the men
      classified as obese. Past-year TF consumption was 100%, and 41% of participants
      reported eating TF on the 24-h recall. TF intake as reported on both the FFQs and
      the 24-h recalls was higher in individuals aged >50 years of age and in men,
      relative to younger adults and women, respectively. TF consumption increased
      protein, vitamin D, iron, and magnesium in all individuals, and energy,
      cholesterol, magnesium, sodium, and zinc in men aged 19-50 years; it decreased
      vitamin C in men and women aged >=51 years. Participants reported drinking a mean
      daily 0.78 +/- 1.34 cans of soft drinks or other high-sugar beverages per day or
      5.28% +/- 8.92% of total energy. It is important to identify behaviours that are
      contributing to obesity and its health consequences in this population and to
      find culturally appropriate ways to promote the consumption of TF and to reduce
      the consumption of energy-dense and nutrient-poor beverages and food items.

PMID- 23537023
TI  - Validation of jump squats as a practical measure of post-activation potentiation.
AB  - To determine if post-activation potentiation (PAP) can augment sports
      performance, it is pertinent that researchers be confident that any enhancement
      in performance is attributable to the PAP phenomenon. However, obtaining
      mechanistic measures of PAP in the daily training environment of highly trained
      athletes is impractical. We sought to validate jump squats as a practical measure
      with ecological validity to sports performance against a mechanistic measure of
      PAP. We assessed the evoked muscle twitch properties of the knee extensors and
      jump squat kinetics of 8 physically trained males in response to a 5-repetition
      maximum back squat conditioning stimulus (CS). Evoked muscle twitch, followed by
      3 jump squats, was assessed before and at 4, 8, and 12 min post CS. Time
      intervals were assessed on separate occasions using a Latin square design. Linear
      regression was used to determine the relationship between post-pre changes in
      kinetic variables and muscle twitch peak force (Ft) and twitch rate of force
      development (RFDt). Large correlations were observed for both concentric relative
      and absolute mean power and Ft (r = 0.50 +/- 0.30) and RFDt (r = 0.56 +/- 0.27
      and r = 0.58 +/- 0.26). Concentric rate of force development (RFD) showed
      moderate correlations with Ft (r = 0.45 +/- 0.33) and RFDt (r = 0.49 +/- 0.32).
      Small-to-moderate correlations were observed for a number of kinetic variables (r
      = -0.42-0.43 +/- 0.32-0.38). Jump squat concentric mean power and RFD are valid
      ecological measures of muscle potentiation, capable of detecting changes in
      athletic performance in response to the PAP phenomenon.

PMID- 23537024
TI  - Effects of carbohydrate ingestion during exercise on substrate oxidation in
      physically active women with different body compositions.
AB  - We examined the effects of consuming a 6% carbohydrate (CHO) beverage during
      exercise on substrate oxidation in active, young Caucasian women with higher body
      fat (HF) (>25%) and lower body fat (LF) (<25%). The HF group (n = 9) had 32.4% +/
      5.6% fat and the LF group (n = 8) had 20.0% +/- 3.0% fat. Subjects completed 2
      sessions of 45 min of treadmill exercise at 55% of maximal oxygen consumption.
      Immediately prior to and at 15-min intervals during exercise, subjects consumed
      25% of a total volume of a CHO beverage (1 g CHO.kg(-1)) or a placebo (PLC).
      During exercise and for 2 h after exercise, expired gases were analyzed to
      determine oxidation rates for CHO (CHO-OX) and fat (FAT-OX). During exercise,
      significant differences (p < 0.05) in CHO-OX (mg.kg fat-free mass(-1).min(-1))
      were found between groups for the CHO trial (LF, 35.4 +/- 4.7 vs. HF, 29.8 +/-
      3.6) and the PLC trial (LF, 33.7 +/- 6.4 vs. HF, 26.3 +/- 4.3). CHO-OX was
      significantly higher during the first hour of recovery in both the LF group (CHO,
      9.3 +/- 2.1 vs. PLC, 5.3 +/- 2.4) and the HF group (CHO, 8.7 +/- 2.0 vs. PLC, 4.2
      +/- 1.0), but during the second hour of recovery, only the HF group had a higher
      CHO-OX (CHO, 5.3 +/- 1.8 vs. PLC, 3.9 +/- 1.1). FAT-OX was significantly lower
      during the first hour of recovery in both the LF group (CHO, 0.6 +/- 0.4 vs. PLC,
      1.0 +/- 0.4) and the HF group (CHO, 0.4 +/- 0.4 vs. PLC, 1.4 +/- 0.4), as well as
      during the second hour of recovery in both the LF group (CHO, 0.8 +/- 0.4 vs.
      PLC, 1.3 +/- 0.5) and the HF group (CHO, 0.9 +/- 0.6 vs. PLC, 1.6 +/- 0). CHO
      ingestion promotes CHO-OX and suppresses FAT-OX during and following exercise in
      physically active women with low and high levels of body fat.

PMID- 23537025
TI  - Anthropometric and dietary predictors of insulin sensitivity in 10- to 14-year
      old boys and girls.
AB  - The high prevalence of pediatric obesity has made preventing chronic diseases
      through healthy lifestyle behaviours a priority within pediatrics. Examining the
      association between diet and insulin sensitivity (IS) in youth may provide
      important insights for tailoring preventative dietary interventions. The
      objective of this study was to explore the associations among anthropometry,
      diet, and IS in 10- to 14-year-olds. In this cross-sectional study, the primary
      outcome measure was IS, measured noninvasively using a (13)C glucose breath test.
      Exposure variables included body mass index (BMI) z score and several dietary
      variables, including glycemic index (GI), glycemic load, and fiber, magnesium,
      vegetable and fruit, and fat intakes, all of which were derived from a validated,
      Web-based 24-h recall tool. Multiple regression analyses were performed for boys
      and girls separately. In total, 378 students (227 girls) aged 12.1 +/- 1.2 years
      were studied. In this sample ~24% of youth were considered overweight or obese
      (BMI z score = 0.41 +/- 0.93). Multiple regression analyses showed that BMI z
      score was negatively and independently associated with (13)C insulin sensitivity
      score ((13)CISS) in both boys and girls (boys: beta = -0.501; girls: beta = 
      0.446; both p < 0.001). GI was negatively and independently related to (13)CISS
      in boys (beta = -0.195, p < 0.05) but not in girls. Other dietary variables were
      not associated with IS. In addition to BMI z score, a low GI diet predicted
      (13)CISS in boys but not in girls. This finding suggests that interventions that
      reduce BMI (in both sexes) and include a low GI diet among boys may improve IS.

PMID- 23537026
TI  - High-intensity interval training increases intrinsic rates of mitochondrial fatty
      acid oxidation in rat red and white skeletal muscle.
AB  - High-intensity interval training (HIIT) can increase mitochondrial volume in
      skeletal muscle. However, it is unclear whether HIIT alters the intrinsic
      capacity of mitochondrial fatty acid oxidation, or whether such changes are
      associated with changes in mitochondrial FAT/CD36, a regulator of fatty acid
      oxidation, or with reciprocal changes in the nuclear receptor coactivator
      (peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC
      1alpha)) and the corepressor (receptor-interacting protein 140 (RIP140)). We
      examined whether HIIT alters fatty acid oxidation rates in the isolated
      subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria of red and white
      skeletal muscle and (or) induces changes in muscle PGC-1alpha and RIP140 proteins
      and mitochondrial FAT/CD36 protein content. Rats were divided into untrained or
      HIIT-trained groups. HIIT animals performed 10 bouts of 1-min high-intensity
      treadmill running (30-55 m.min(-1)), separated by 2 min of rest, for 5 days a
      week for 4 weeks. As expected, after the training period, HIIT increased
      mitochondrial enzymes (citrate synthase, COXIV, and beta-hydroxyacyl CoA
      dehydrogenase) in red and white muscle, indicating that muscle mitochondrial
      volume had increased. HIIT also increased the rates of palmitate oxidation in
      mitochondria of red (37% for SS and 19% for IMF) and white (36% for SS and 12%
      for IMF) muscle. No changes occurred in SS and IMF mitochondrial FAT/CD36
      proteins, despite increasing FAT/CD36 at the whole-muscle level (27% for red and
      22% for white). Concurrently, muscle PGC-1alpha protein was increased in red
      (22%) and white (16%) muscle, but RIP140 was not altered. These results indicate
      that increases in SS and IMF mitochondrial fatty acid oxidation induced by HIIT
      are accompanied by an increase in PGC-1alpha, but not RIP140 or FAT/CD36.

PMID- 23537027
TI  - Nonalcoholic fatty liver disease is associated with lower hepatic and erythrocyte
      ratios of phosphatidylcholine to phosphatidylethanolamine.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with altered hepatic lipid
      composition. Animal studies suggest that the hepatic ratio of phosphatidylcholine
      (PC) to phosphatidylethanolamine (PE) contributes to steatogenesis and
      inflammation. This ratio may be influenced by dysregulation of the PE N
      methyltransferase (PEMT) pathway or by a low-choline diet. Alterations in the
      liver may also influence lipid composition in circulation such as in
      erythrocytes, which therefore may have utility as a biomarker of hepatic disease.
      Currently, no study has assessed both liver and erythrocyte PC/PE ratios in
      NAFLD. The aim of this study was to compare the PC/PE ratio in the liver and
      erythrocytes of patients with simple steatosis (SS) or nonalcoholic
      steatohepatitis (NASH) with that of healthy controls. PC and PE were measured by
      mass spectrometry in 28 patients with biopsy-proven NAFLD (14 SS, 14 NASH) and 9
      healthy living liver donors as controls. The hepatic PC/PE ratio was lower in SS
      patients (median [range]) (1.23 [0.27-3.40]) and NASH patients (1.29 [0.77-3.22])
      compared with controls (3.14 [2.20-3.73]); both p < 0.001) but it was not
      different between SS and NASH. PC was lower and PE higher in the liver of SS
      patients compared with controls, whereas in NASH patients only PE was higher. The
      PC/PE ratio in erythrocytes was also lower in SS and NASH patients compared with
      controls because of lower PC in both patient groups. PE in erythrocytes was not
      different among the groups. In conclusion, NAFLD patients have a lower PC/PE
      ratio in the liver and erythrocytes than do healthy controls, which may play a
      role in the pathogenesis. The underlying mechanisms require further
      investigation.

PMID- 23537028
TI  - Effect of adding single-joint exercises to a multi-joint exercise resistance
      training program on strength and hypertrophy in untrained subjects.
AB  - The aim of this study was to examine the effect of adding single-joint (SJ)
      exercises to a multi-joint (MJ) exercise resistance-training program on upper
      body muscle size and strength. Twenty-nine untrained young men participated in a
      10-week training session. They were randomly divided in 2 groups: the MJ group
      performed only MJ exercises (lat pulldown and bench press); the MJ+SJ group
      performed the same MJ exercises plus SJ exercises (lat pulldown, bench press,
      elbow flexion, and elbow extension). Before and after the training period, the
      muscle thickness (MT) of the elbow flexors was measured with ultrasound, and peak
      torque (PT) was measured with an isokinetic dynamometer. There was a significant
      (p < 0.05) increase in MT (6.5% for MJ and 7.04% for MJ+SJ) and PT (10.40% for MJ
      and 12.85% for MJ+SJ) in both groups, but there were no between-group
      differences. Therefore, this study showed that the inclusion of SJ exercises in a
      MJ exercise training program resulted in no additional benefits in terms of
      muscle size or strength gains in untrained young men.

PMID- 23537029
TI  - Tri-axial high-resolution acceleration for oxygen uptake estimation: Validation
      of a multi-sensor device and a novel analysis method.
AB  - We validated a multi-sensor chest-strap against indirect calorimetry and further
      introduced the total-acceleration-variability (TAV) method for analyzing high
      resolution accelerometer data. Linear regression models were developed to predict
      oxygen uptake from the TAV-processed multi-sensor data. Individual correlations
      between observed and TAV-predicted oxygen uptake (VO2) were strong (mean r =
      0.94) and bias low (1.5 mL.min(-1).kg(-1), p < 0.01; 95% confidence interval: 8.7
      mL.min(-1).kg(-1); -5.8 mL.min(-1).kg(-1)); however, caution should be taken when
      a single-model value is used as a surrogate for VO2.

PMID- 23537030
TI  - Measuring slope to improve energy expenditure estimates during field-based
      activities.
AB  - This technical note describes methods to improve activity energy expenditure
      estimates by using a multi-sensor board (MSB) to measure slope. Ten adults walked
      over a 4-km (2.5-mile) course wearing an MSB and mobile calorimeter. Energy
      expenditure was estimated using accelerometry alone (base) and 4 methods to
      measure slope. The barometer and global positioning system methods improved
      accuracy by 11% from the base (p < 0.05) to 86% overall. Measuring slope using
      the MSB improves energy expenditure estimates during field-based activities.

PMID- 23537038
TI  - Primary pulmonary primitive neuroectodermal tumor metastasis to the pancreas: a
      rare case with seven-year follow-up.
AB  - There are only nine primitive neuroectodermal tumor (PNET) cases that have arisen
      in lung parenchyma without pleural or chest wall involvement in the literature.
      Here, we present a long-term survival case of pulmonary PNET. A pulmonary mass
      was detected in a 19-year-old man on a chest radiograph and computed tomography
      image. At the three-year follow-up, the mass had enlarged in diameter by two
      fold. The lesion was resected via lower left lobectomy. Histologically, the tumor
      was composed of uniform cells with round nuclei and scanty cytoplasm arranged in
      lobules with rosettes and pseudorosettes formation. Immunohistochemically, the
      tumor was positive for CD99, vimentin, neuron specific enolase and chromogranin
      A, and negative for cytokeratins, CD3, desmin, and leukocyte common antigen.
      Pancreatic metastasis occurred sixteen months after the first surgery, which was
      managed by pancreatectomy. The patient has survived seven years after the mass
      was initially detected, and four years after the first lobectomy. VIRTUAL SLIDES:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1500847644913244.

PMID- 23537039
TI  - Deficiency of ADAMTS-13 in pediatric patients with severe sepsis and impact on in
      hospital mortality.
AB  - BACKGROUND: The enzyme involved in regulating the size of vWF (von Willebrand
      factor) in plasma is ADAMTS-13 (A disintegrin and metalloprotease with
      thrombospondin type-1 motives). Deficient proteolysis of ULvWF (ultra large von
      Willebrand factor) due to reduced ADAMTS-13 activity results in disseminated
      platelet-rich thrombi in the microcirculation characteristic of thrombotic
      thrombocytopenic purpura. Reduced ADAMTS-13 has also been observed in severe
      sepsis and is associated with poor survival. We conducted this study to detect
      ADAMTS-13 deficiency and its impact on in-hospital mortality in pediatric
      patients with severe sepsis. METHODS: Pediatric patients diagnosed with severe
      sepsis were recruited for the study. Baseline clinical characteristics were
      noted. ADAMTS-13 antigen levels were assayed by ELISA. According to ADAMTS-13
      levels, patients were grouped as deficient and non-deficient. Comparison was done
      with regard to some clinical and biological characteristics and in-hospital
      mortality between the two groups. RESULTS: A total of 80 patients were enrolled
      in the study. The median age of the patients was 3.1 years (Range: 0.1-15 years).
      ADAMTS-13 deficiency with levels less than 350 ng/dl was found in 65% patients.
      In patients with ADAMTS-13 deficiency, 75.6% had low platelets of less than 150 *
      109/L. In-hospital mortality was 42.3% and 35.7% in ADAMTS-13 deficient and non
      deficient group, respectively. CONCLUSION: Majority of the pediatric patients
      admitted to hospital with severe sepsis exhibit ADAMTS-13 deficiency. ADAMTS-13
      deficiency might play a role in sepsis-induced thrombocytopenia. More studies are
      needed to evaluate the role of ADAMTS-13 deficiency on in-hospital mortality.

PMID- 23537040
TI  - cAMP-stimulated Cl- secretion is increased by glucocorticoids and inhibited by
      bumetanide in semicircular canal duct epithelium.
AB  - BACKGROUND: The vestibular system controls the ion composition of its luminal
      fluid through several epithelial cell transport mechanisms under hormonal
      regulation. The semicircular canal duct (SCCD) epithelium has been shown to
      secrete Cl- under beta2-adrenergic stimulation. In the current study, we sought
      to determine the ion transporters involved in Cl- secretion and whether secretion
      is regulated by PKA and glucocorticoids. RESULTS: Short circuit current (Isc)
      from rat SCCD epithelia demonstrated stimulation by forskolin (EC50: 0.8 MUM), 8
      Br-cAMP (EC50: 180 MUM), 8-pCPT-cAMP (100 MUM), IBMX (250 MUM), and RO-20-1724
      (100 MUM). The PKA activator N6-BNZ-cAMP (0.1, 0.3 & 1 mM) also stimulated Isc.
      Partial inhibition of stimulated Isc individually by bumetanide (10 & 50 MUM),
      and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 MUM) were additive and
      complete. Stimulated Isc was also partially inhibited by CFTRinh-172 (5 & 30
      MUM), flufenamic acid (5 MUM) and diphenylamine-2,2'-dicarboxylic acid (DPC; 1
      mM). Native canals of CFTR+/- mice showed a stimulation of Isc from isoproterenol
      and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while
      canals from CFTR-/- mice had no responses. Nonetheless, CFTR-/- mice showed no
      difference from CFTR+/- mice in their ability to balance (rota-rod). Stimulated
      Isc was greater after chronic incubation (24 hr) with the glucocorticoids
      dexamethasone (0.1 & 0.3 MUM), prednisolone (0.3, 1 & 3 MUM), hydrocortisone
      (0.01, 0.1 & 1 MUM), and corticosterone (0.1 & 1 MUM) and mineralocorticoid
      aldosterone (1 MUM). Steroid action was blocked by mifepristone but not by
      spironolactone, indicating all the steroids activated the glucocorticoid, but not
      mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a,
      KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very
      low WNK4 was determined. CONCLUSIONS: These results are consistent with a model
      of Cl- secretion whereby Cl- is taken up across the basolateral membrane by a Na+
      K+-2Cl- cotransporter (NKCC) and potentially another transporter, is secreted
      across the apical membrane via a Cl- channel, likely CFTR, and demonstrate the
      regulation of Cl- secretion by protein kinase A and glucocorticoids.

PMID- 23537041
TI  - Cardioprotective effects of lixisenatide in rat myocardial ischemia-reperfusion
      injury studies.
AB  - BACKGROUND: Lixisenatide is a glucagon-like peptide-1 analog which stimulates
      insulin secretion and inhibits glucagon secretion and gastric emptying. We
      investigated cardioprotective effects of lixisenatide in rodent models reflecting
      the clinical situation. METHODS: The acute cardiac effects of lixisenatide were
      investigated in isolated rat hearts subjected to brief ischemia and reperfusion.
      Effects of chronic treatment with lixisenatide on cardiac function were assessed
      in a modified rat heart failure model after only transient coronary occlusion
      followed by long-term reperfusion. Freshly isolated cardiomyocytes were used to
      investigate cell-type specific mechanisms of lixisenatide action. RESULTS: In the
      acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area
      at risk by 36% ratio without changes on coronary flow, left-ventricular pressure
      and heart rate. Treatment with lixisenatide for 10 weeks, starting after cardiac
      ischemia and reperfusion, improved left ventricular end-diastolic pressure and
      relaxation time and prevented lung congestion in comparison to placebo. No anti
      fibrotic effect was observed. Gene expression analysis revealed a change in
      remodeling genes comparable to the ACE inhibitor ramipril. In isolated
      cardiomyocytes lixisenatide reduced apoptosis and increased fractional
      shortening. Glucagon-like peptide-1 receptor (GLP1R) mRNA expression could not be
      detected in rat heart samples or isolated cardiomyocytes. Surprisingly,
      cardiomyocytes isolated from GLP-1 receptor knockout mice still responded to
      lixisenatide. CONCLUSIONS: In rodent models, lixisenatide reduced in an acute
      setting infarct-size and improved cardiac function when administered long-term
      after ischemia-reperfusion injury. GLP-1 receptor independent mechanisms
      contribute to the described cardioprotective effect of lixisenatide. Based in
      part on these preclinical findings patients with cardiac dysfunction are
      currently being recruited for a randomized, double-blind, placebo-controlled,
      multicenter study with lixisenatide. TRIAL REGISTRATION: (ELIXA,
      ClinicalTrials.gov Identifier: NCT01147250).

PMID- 23537042
TI  - Protective and therapeutic potency of N-acetyl-cysteine on propionic acid-induced
      biochemical autistic features in rats.
AB  - BACKGROUND: The investigation of the environmental contribution for developmental
      neurotoxicity is very critical. Many environmental chemical exposures are now
      thought to contribute to the development of neurological disorders, especially in
      children. Results from animal studies may guide investigations of human
      populations towards identifying either environmental toxicants that cause or
      drugs that protect from neurotoxicity and may help in treatment of
      neurodevelopmental disorders. OBJECTIVE: To study both the protective and
      therapeutic effects of N-acetyl cysteine on brain intoxication induced by
      propionic acid (PPA) in rats. METHODS: Twenty-eight young male Western Albino
      rats were enrolled in the present study. They were grouped into four equal
      groups, each of 7 animals. Group 1: control group, orally received only phosphate
      buffered saline; Group 2: PPA-treated group, received a neurotoxic dose of of PPA
      of 250 mg/kg body weight/day for 3 days; Group 3: protective group, received a
      dose of 50 mg/kg body weight/day N-acetyl-cysteine for one week followed by a
      similar dose of PPA for 3 days; and Group 4: therapeutic group, treated with the
      same dose of N-acetyl cysteine after being treated with the toxic dose of PPA.
      Serotonin, interferon gamma (IFN-gamma), and glutathione-s-transferase activity,
      together with Comet DNA were assayed in the brain tissue of rats in all different
      groups. RESULTS: The obtained data showed that PPA caused multiple signs of brain
      toxicity as measured by depletion of serotonin (5HT), increase in IFN-gamma and
      inhibition of glutathione-s-transferase activity as three biomarkers of brain
      dysfunction. Additionally Comet DNA assay showed remarkably higher tail length,
      tail DNA % damage and tail moment. N-acetyl-cysteine was effective in
      counteracting the neurotoxic effects of PPA. CONCLUSIONS: The low dose and the
      short duration of N-acetyl-cysteine treatment tested in the present study showed
      much more protective rather than therapeutic effects on PPA-induced neurotoxicity
      in rats, as there was a remarkable amelioration in the impaired biochemical
      parameters representing neurochemical, inflammatory, detoxification and DNA
      damage processes.

PMID- 23537043
TI  - The metabolic costs of improving ethanol yield by reducing glycerol formation
      capacity under anaerobic conditions in Saccharomyces cerevisiae.
AB  - BACKGROUND: Finely regulating the carbon flux through the glycerol pathway by
      regulating the expression of the rate controlling enzyme, glycerol-3-phosphate
      dehydrogenase (GPDH), has been a promising approach to redirect carbon from
      glycerol to ethanol and thereby increasing the ethanol yield in ethanol
      production. Here, strains engineered in the promoter of GPD1 and deleted in GPD2
      were used to investigate the possibility of reducing glycerol production of
      Saccharomyces cerevisiae without jeopardising its ability to cope with process
      stress during ethanol production. For this purpose, the mutant strains TEFmut7
      and TEFmut2 with different GPD1 residual expression were studied in Very High
      Ethanol Performance (VHEP) fed-batch process under anaerobic conditions. RESULTS:
      Both strains showed a drastic reduction of the glycerol yield by 44 and 61% while
      the ethanol yield improved by 2 and 7% respectively. TEFmut2 strain showing the
      highest ethanol yield was accompanied by a 28% reduction of the biomass yield.
      The modulation of the glycerol formation led to profound redox and energetic
      changes resulting in a reduction of the ATP yield (YATP) and a modulation of the
      production of organic acids (acetate, pyruvate and succinate). Those metabolic
      rearrangements resulted in a loss of ethanol and stress tolerance of the mutants,
      contrarily to what was previously observed under aerobiosis. CONCLUSIONS: This
      work demonstrates the potential of fine-tuned pathway engineering, particularly
      when a compromise has to be found between high product yield on one hand and
      acceptable growth, productivity and stress resistance on the other hand. Previous
      study showed that, contrarily to anaerobiosis, the resulting gain in ethanol
      yield was accompanied with no loss of ethanol tolerance under aerobiosis.
      Moreover those mutants were still able to produce up to 90 gl-1 ethanol in an
      anaerobic SSF process. Fine tuning metabolic strategy may then open encouraging
      possibilities for further developing robust strains with improved ethanol yield.

PMID- 23537044
TI  - Polycythemia vera revealed via a bladder tumor in a patient with erectile
      dysfunction: a case report.
AB  - INTRODUCTION: Polycythemia vera is a polyglobular myeloproliferative syndrome
      related to the mutation of multipotent hemopoietic stem cells. This case report
      describes a patient whose bladder tumor was associated with polycythemia vera and
      erectile dysfunction. The association of bladder neoplasia with polycythemia vera
      and erectile dysfunction has not previously been reported in the literature. CASE
      PRESENTATION: A 40-year-old Moroccan man was followed up for a bladder tumor
      which manifested with coagulant hematuria and a facial erythrosis with a
      hemoglobin level of 20.3g/L suggesting polycythemia vera. The patient also
      suffered from an erectile disorder. Considering the anesthesia difficulty due to
      polyglobulia, the patient was treated by bleeding. This treatment enabled the
      patient's sexual performance to be improved and adjustment of his hemoglobin to a
      level allowing anesthesia, and hence surgical resection of his bladder tumor.
      CONCLUSION: Erectile dysfunction associated with polycythemia vera is elucidated
      by rheological disorders. Bleeding contributed to satisfactory sexual performance
      and facilitated treatment of polycythemia vera because it enabled anesthesia to
      be performed and hence the surgical resection of the bladder tumor.

PMID- 23537045
TI  - From the Zeno's paradoxes to novel immunotherapeutic agents for kidney cancer:
      moving from an era of wrong premises and conclusions to a better comprehension of
      immunology.

PMID- 23537046
TI  - Transcriptome analysis of the parasite Encephalitozoon cuniculi: an in-depth
      examination of pre-mRNA splicing in a reduced eukaryote.
AB  - BACKGROUND: The microsporidian Encephalitozoon cuniculi possesses one of the most
      reduced and compacted eukaryotic genomes. Reduction in this intracellular
      parasite has affected major cellular machinery, including the loss of over fifty
      core spliceosomal components compared to S. cerevisiae. To identify expression
      changes throughout the parasite's life cycle and also to assess splicing in the
      context of this reduced system, we examined the transcriptome of E. cuniculi
      using Illumina RNA-seq. RESULTS: We observed that nearly all genes are expressed
      at three post-infection time-points examined. A large fraction of genes are
      differentially expressed between the first and second (37.7%) and first and third
      (43.8%) time-points, while only four genes are differentially expressed between
      the latter two. Levels of intron splicing are very low, with 81% of junctions
      spliced at levels below 50%. This is dramatically lower than splicing levels
      found in two other fungal species examined. We also describe the first case of
      alternative splicing in a microsporidian, an unexpected complexity given the
      reduction in spliceosomal components. CONCLUSIONS: Low levels of splicing
      observed are likely the result of an inefficient spliceosome; however, at least
      in one case, splicing appears to be playing a functional role. Although several
      RNA decay genes are encoded in E. cuniculi, the lack of a few key players could
      be reducing decay levels and therefore increasing the proportion of unspliced
      transcripts. Significant proportions of genes are differentially expressed in the
      first forty-eight hours but not after, indicative of genetic changes that precede
      the intracellular to infective stage transition.

PMID- 23537047
TI  - Cancer antibody enhanced real time imaging cell probes--a novel theranostic tool
      using polymer linked carbon nanotubes and quantum dots.
AB  - BACKGROUND: Cancer is a potentially fatal diagnosis, but due to modern medicine
      there is a potential cure in many of these cases. The rate of treatment success
      depends on early disease detection and timely, effective delivery of tumour
      specific treatment. There are many ongoing researches aimed to improve
      diagnostics or treatment, but the option to use both modalities concomitantly is
      deficient. In this project we are using the advances in nanotechnology to develop
      new theranostic tool using single walled carbon nanotubes (SWCNT) and Quantum
      dots (QDs) for early cancer cell detection, and option to deliver targeted
      treatment. METHOD: SWCNTs were refluxed in HNO3/H2SO4 (1:3) at 120oC for 120
      minutes. Functionalised SWCNT was then covalently attached to octa-ammonium
      polyhedral oligomeric silsesquioxane (POSS), QDs and conjugated with antibodies
      for targeted cell detection. Fourier transforms infrared spectroscopy (FTIR),
      Transmission electron microscopy (TEM), UV/NIR analysis, Raman and UV-VIS
      spectroscopy were used in order to prove the successful conjugation. Toxicology
      study using alamar blue analysis and DNA assay was conducted in order to choose
      the best concentration of SWCNT, octa-ammonium-POSS and QDs before commencing the
      conjugation process. Human colorectal cancer cell line HT29, pancreas cancer cell
      line PANC-1 and mouse fibroblasts 3T3 were then treated with or without antibody
      conjugated SWCNT-POSS-QDs (CPQ) compound solution. The cell response was observed
      under the microscope after 24, 48 and 72 hours. RESULTS: FTIR and Raman
      spectroscopies confirmed covalent binding of the SWCNTs to Octa-Ammonium-POSS.
      This was supported by TEM images and photos obtained, which showed well dispersed
      SWCNTs following its treatment with Octa-Ammonium-POSS compared to pristine SWCNT
      samples. UV-VIS graphs determined the presence of antibody within the compound.
      UV/NIR demonstrated QD fluorescence even after attachment of SWCNT-POSS. The
      cellular behaviour revealed high CPQ-antibody complex affinity towards cancer
      cells when compared to healthy cell line which internalised the complex only on
      day three. The pancreas cancer cell line had appearance of lysed pulp after 72
      hours of incubation. Colonic cancer cells seemed to regain ability to populate
      from day three signifying that higher treatment payload is necessary. CONCLUSION:
      We have successfully manufactured novel compound consisting of Octa-Ammonium-POSS
      linked SWCNTs, QDs, and tumour specific antibodies. The complex has proven its
      potential as cell probing tool, and the attachment of antibodies has shown high
      affinity to cancer cells rendering this an attractive model for further
      theranostic developments.

PMID- 23537048
TI  - From Na+/K+-ATPase and cardiac glycosides to cytotoxicity and cancer treatment.
AB  - The cardiac glycosides are a group of compounds isolated from plants and some
      animals. They have been used in therapy for heart failure for many years. The
      cytotoxic effect of many cardiac glycosides has been demonstrated, but the
      mechanism of action is very complicated and complex, and Na+/K+-ATPase surely
      plays a crucial role in it. On the other hand, Na+/K+-ATPase is regulated by many
      endogenous factors, such as hormones or FXYD proteins, whose role in regulating
      the cell cycle has been studied intensively. This review focuses on the role of
      Na+/K+-ATPase in regulating the cell growth, the cell cycle and the cell
      proliferation and on the involvement of cardiac glycosides in regulating Na+/K+
      ATPase. The cytotoxic effect of cardiac glycosides is discussed with respect to
      the apoptotic mechanisms possibly induced by these compounds. Novel strategies in
      cancer therapy based on cardiac glycosides are discussed as are possibilities for
      counteracting multidrug resistance by using cardiac glycosides. The aim of this
      review is to present cardiac glycosides not only as pharmaceuticals used in the
      management of heart failure, but also as potent cytotoxic agents with potential
      uses in cancer treatment. 

PMID- 23537050
TI  - Eyeing the eyes in social scenes: Evidence for top-down control of stimulus
      selection in simultanagnosia.
AB  - Simultanagnosia is a disorder of visual attention resulting from bilateral
      parieto-occipital lesions. Healthy individuals look at eyes to infer people's
      attentional states, but simultanagnosics allocate abnormally few fixations to
      eyes in scenes. It is unclear why simultanagnosics fail to fixate eyes, but it
      might reflect that they are (a) unable to locate and fixate them, or (b) do not
      prioritize attentional states. We compared eye movements of simultanagnosic G.B.
      to those of healthy subjects viewing scenes normally or through a restricted
      window of vision. They described scenes and explicitly inferred attentional
      states of people in scenes. G.B. and subjects viewing scenes through a restricted
      window made few fixations on eyes when describing scenes, yet increased fixations
      on eyes when inferring attention. Thus G.B. understands that eyes are important
      for inferring attentional states and can exert top-down control to seek out and
      process the gaze of others when attentional states are of interest.

PMID- 23537051
TI  - Airway dimensions in fatal asthma and fatal COPD: overlap in older patients.
AB  - In some patients with chronic asthma clinical and physiological similarities with
      COPD may exist, such as partial reversibility to bronchodilators and persistent
      expiratory airflow obstruction. However, pathological data comparing both
      diseases in patients of similar age and disease severity are scarce. We compared
      large and small airway dimensions in 12 younger (mean age 32 yrs) and 15 older
      (mean age 65 yrs) non-smoker adult fatal asthma patients with 14 chronic smokers
      with severe, fatal COPD (mean age 71 yrs). Using H&E, Movat pentachrome staining
      and image analysis, we quantified large airway basement membrane (BM) thickness
      (MUm), submucosal gland area and large and small airway inner wall, smooth muscle
      and outer wall areas. Areas were normalized by BM perimeter (MUm(2)/MUm). Younger
      adult fatal asthma patients had thicker BM, smooth muscle, and outer wall areas
      in both small and large airways when compared to COPD patients. In older
      asthmatics there was an overlap in BM thickness and airway structure in small
      airways. Inner wall layer in large and small airway level and submucosal gland
      areas were similar among groups. In conclusion, there are airway histological
      structural similarities between fatal asthma and fatal COPD. Older fatal
      asthmatics present overlapping airway structural features with younger adult
      fatal asthmatics and severe COPD patients. Our data contributes to a better
      understanding of asthma pathology in the elderly.

PMID- 23537049
TI  - Draft genome of the mountain pine beetle, Dendroctonus ponderosae Hopkins, a
      major forest pest.
AB  - BACKGROUND: The mountain pine beetle, Dendroctonus ponderosae Hopkins, is the
      most serious insect pest of western North American pine forests. A recent
      outbreak destroyed more than 15 million hectares of pine forests, with major
      environmental effects on forest health, and economic effects on the forest
      industry. The outbreak has in part been driven by climate change, and will
      contribute to increased carbon emissions through decaying forests. RESULTS: We
      developed a genome sequence resource for the mountain pine beetle to better
      understand the unique aspects of this insect's biology. A draft de novo genome
      sequence was assembled from paired-end, short-read sequences from an individual
      field-collected male pupa, and scaffolded using mate-paired, short-read genomic
      sequences from pooled field-collected pupae, paired-end short-insert whole
      transcriptome shotgun sequencing reads of mRNA from adult beetle tissues, and
      paired-end Sanger EST sequences from various life stages. We describe the
      cytochrome P450, glutathione S-transferase, and plant cell wall-degrading enzyme
      gene families important to the survival of the mountain pine beetle in its harsh
      and nutrient-poor host environment, and examine genome-wide single-nucleotide
      polymorphism variation. A horizontally transferred bacterial sucrose-6-phosphate
      hydrolase was evident in the genome, and its tissue-specific transcription
      suggests a functional role for this beetle. CONCLUSIONS: Despite Coleoptera being
      the largest insect order with over 400,000 described species, including many
      agricultural and forest pest species, this is only the second genome sequence
      reported in Coleoptera, and will provide an important resource for the
      Curculionoidea and other insects.

PMID- 23537053
TI  - Cooling down climate change, while heating up grocery bills: ES&T's top policy
      analysis article 2012.

PMID- 23537052
TI  - An assessment of the vulnerability of carotid plaques: a comparative study
      between intraplaque neovascularization and plaque echogenicity.
AB  - BACKGROUND: Carotid plaque echolucency as detected by Color Doppler
      ultrasonography (CDUS) has been used as a potential marker of plaque
      vulnerability. However, contrast-enhanced ultrasound (CEUS) has recently been
      shown to be a valuable method to evaluate the vulnerability and
      neovascularization within carotid atherosclerotic plaques. The aim of this study
      was to compare CEUS and CDUS in the assessment of plaque vulnerability using
      transcranial color Doppler (TCD) monitoring of microembolic signals (MES) as a
      reference technique. METHODS: A total of 46 subjects with arterial stenosis (>=
      50%) underwent a carotid duplex ultrasound, TCD monitoring of MES and CEUS
      (SonoVue doses of 2.0 mL) within a span of 3 days. The agreement between the
      CEUS, CDUS, and MES findings was assessed with a chi-square test. A p-value less
      than 0.05 was considered statistically significant. RESULTS: Neovascularization
      was observed in 30 lesions (44.4%). The vascular risk factors for stroke were
      similar and there were no age or gender differences between the 2 groups. Using
      CEUS, MES were identified in 2 patients (12.5%) within class 1 (non
      neovascularization) as opposed to 15 patients (50.0%) within class 2
      (neovascularization) (p = 0.023). CDUS revealed no significant differences in the
      appearance of the MES between the 2 groups (hyperechoic and hypoechoic) (p =
      0.237). CONCLUSION: This study provides preliminary evidence to suggest that
      intraplaque neovascularization detected by CEUS is associated with the presence
      of MESs, where as plaque echogenicity on traditional CDUS does not. These
      findings argue that CEUS may better identify high-risk plaques.

PMID- 23537054
TI  - The EPMA Journal introduces a new type of research article dedicated to
      predictive, preventive and personalised medicine.

PMID- 23537055
TI  - Correlation queries for mass spectrometry imaging.
AB  - Mass spectrometry imaging (MSI) generates large volumetric data sets consisting
      of mass to charge ratio (m/z), ion current, and x,y coordinate location. These
      data sets usually serve limited purposes centered on measuring the distribution
      of a small set of ions with known m/z. Such earmarked queries consider only a
      fraction of the full mass spectrum captured, and there are few tools to assist
      the exploration of the remaining volume of unknown data in terms of demonstrating
      similarity or discordance in tissue compartment distribution patterns. Here we
      present a novel, interactive approach to extract information from MSI data that
      relies on precalculated data structures to perform queries of large data sets
      with a typical laptop. We have devised methods to query the full volume to find
      new m/z values of potential interest based on similarity to biological structures
      or to the spatial distribution of known ions. We describe these query methods in
      detail and provide examples demonstrating the power of the methods to "discover"
      m/z values of ions that have such potentially interesting correlations. The
      "discovered" ions may be further correlated with either positional locations or
      the coincident distribution of other ions using successive queries. Finally, we
      show it is possible to gain insight to the fragmentation pattern of the parent
      molecule from such correlations. The ability to discover new ions of interest in
      the unknown bulk of an MSI data set offers the potential to further our
      understanding of biological and physiological processes related to health and
      disease. 

PMID- 23537056
TI  - Hepatocellular carcinoma as extracolonic manifestation of Lynch syndrome
      indicates SEC63 as potential target gene in hepatocarcinogenesis.
AB  - OBJECTIVE: Lynch syndrome is a cancer predisposition syndrome caused by germline
      mutations in DNA mismatch repair (MMR) genes with microsatellite instability
      (MSI) as its molecular hallmark. Hepatocellular carcinoma (HCC) has not been
      considered part of the tumor spectrum. The aim was to provide a detailed
      molecular characterization of an HCC associated with Lynch Syndrome (Muir-Torre
      variant). MATERIALS AND METHODS: HCC samples were analyzed for MSI, MMR protein
      expression and coding microsatellite instability (cMSI). Since cMSI also affected
      SEC63 coding for an endoplasmic reticulum membrane protein with implications for
      intracellular protein translocation, its impact on hepatocyte growth control was
      assessed in an established short-term model. Recombinant inbred mouse lines (BXD)
      showing different basal SEC63 expression levels were treated with the
      chemocarcinogen diethylnitrosamine (DEN) intraperitoneally. Proliferation and
      apoptosis of hepatocytes were determined after 48 h using Ki67 and TUNEL assays.
      RESULTS: The HCC was high-grade microsatellite unstable with loss of MSH2
      expression. cMSI was detected in four genes (ASTE1, SEC63, TAF1B, TGFBR2).
      However, only TGFBR2 is known to be involved in hepatocarcinogenesis. When
      investigating the impact of SEC63 expression on hepatocyte growth control in the
      murine model, low hepatic expression correlated significantly (p < 0.05) with a
      decrease in apoptosis and increased proliferative activity. CONCLUSIONS: For the
      first time, an HCC with characteristic molecular features of association with
      Lynch syndrome is described. The pro-carcinogenic growth behavior of hepatocytes
      with low SEC63 expression in the murine model indicates a potential role for
      SEC63 in hepatocarcinogenesis in general, but this needs further functional
      validation.

PMID- 23537057
TI  - Enhanced gas absorption in the ionic liquid 1-n-hexyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)amide ([hmim][Tf2N]) confined in silica slit pores: a
      molecular simulation study.
AB  - Two-dimensional NPxyT and isostress-osmotic (N2PxyTf1) Monte Carlo simulations
      were used to compute the density and gas absorption properties of the ionic
      liquid (IL) 1-n-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide
      ([hmim][Tf2N]) confined in silica slit pores (25-45 A). Self-diffusivity values
      for both gas and IL were calculated from NVE molecular dynamics simulations using
      both smooth and atomistic potential models for silica. The simulations showed
      that the molar volume of [hmim][Tf2N] confined in 25-45-A silica slit pores is 12
      31% larger than that of the bulk IL at 313-573 K and 1 bar. The amounts of CO2,
      H2, and N2 absorbed in the confined IL are 1.1-3 times larger than those in the
      bulk IL because of the larger molar volume of the confined IL compared to the
      bulk IL. The CO2, N2, and H2 molecules are generally absorbed close to the silica
      wall where the IL density is very low. This arrangement causes the self
      diffusivities of these gases in the confined IL to be 2-8 times larger than those
      in the bulk IL at 298-573 K. The solubilities of water in the confined and bulk
      ILs are similar, which is likely due to strong water interactions with
      [hmim][Tf2N] through hydrogen bonding, so that the molar volume of the confined
      IL plays a less important role in determining the H2O solubility. Water molecules
      are largely absorbed in the IL-rich region rather than close to the silica wall.
      The self-diffusivities of water correlate with those of the confined IL. The
      confined IL exhibits self-diffusivities larger than those of the bulk IL at lower
      temperatures, but smaller than those of the bulk IL at higher temperatures. The
      findings from our simulations are consistent with available experimental data for
      similar confined IL systems.

PMID- 23537058
TI  - GHz properties of magnetophoretically aligned iron-oxide nanoparticle doped
      polymers.
AB  - We show that assembled domains of magnetic iron-oxide nanoparticles (IONPs) are
      effective at increasing the dielectric permittivity of polydimethylsiloxane
      (PDMS) nanocomposites in the GHz frequency range. The assembly has been achieved
      by means of magnetophoretic transport and its efficacy, as well as the
      electromagnetic properties of the nanocomposite, has been found to depend on
      IONPs diameter. Remarkably, the dielectric permittivity increase has been
      obtained by keeping dielectric and magnetic losses very low, making us envision
      the suitability of nanocomposites based on aligned IONPs as substrates for
      radiofrequency applications.

PMID- 23537059
TI  - Subacute cutaneous lupus erythematosus in the course of rheumatoid arthritis: a
      relationship with TNF-alpha antagonists and rituximab therapy?
AB  - INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is
      caused by different medicines, first of all: calcium channel blockers,
      angiotensin converting enzyme inhibitors, thiazides, terbinafine, statins and
      antagonists of tumor necrosis factor-alpha (TNF-alpha). DI-SCLE does not
      distinguish from idiopathic form of the disease, clinically, histopathologically
      and immunologically. However, receding of symptoms is observed after recapture of
      the provoking drug. AIM: To present a patient with rheumatoid arthritis (RA), who
      developed SCLE after treatment with TNF-alpha antagonists and rituximab. CASE
      REPORT: In a 31-year-old woman with RA leucopenia due to treatment with
      etanercept and adalimumab was observed. Therefore, the treatment was changed to
      rituximab, but after starting the therapy, erythematous and oedematous skin
      lesions of an oval or annular shape appeared on the cheeks, auricles, lips and
      the decolette. Histopathological evaluation of the skin lesions revealed SCLE.
      Ro/SS-A and La/SS-B antibodies were detected in serum. Regression of skin lesions
      and hematologic disturbances was achieved after starting corticosteroid therapy.
      CONCLUSIONS: Co-existence of SCLE with RA should be considered in some patients.
      The role of TNF-alpha antagonists and rituximab therapy in induction of
      idiopathic form of SCLE requires further investigations.

PMID- 23537060
TI  - Retroperitoneal paraganglioma with metastasis to the abdominal vertebra: a case
      report.
AB  - BACKGROUND: Extra-adrenal paraganglioma of the retroperitoneum with metastasis to
      the vertebra is very rare. To our knowledge this is the first report of this kind
      of disease in the literature. CASE PRESENTATION: Here, we present an oroginal
      case of paraganglioma of the retroperitoneum with metastasis to the abdominal
      vertebra in a 42-year-old female patient who was successfully treated by complete
      removal of the tumor and its metastasis. The patient was followed up for four
      years and remained disease-free. CONCLUSION: Our case demonstrated the need to
      consider paraganglioma of the retroperitoneum in the differential diagnosis of
      retroperitoneal mass, metastatic tumors to the vertebra, and the importance of
      radical surgery for a successful management of the disease. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1956611954880197.

PMID- 23537061
TI  - Inter-observer agreement and diagnostic accuracy of myocardial perfusion reserve
      quantification by cardiovascular magnetic resonance at 3 Tesla in comparison to
      quantitative coronary angiography.
AB  - BACKGROUND: Quantification of cardiovascular magnetic resonance (CMR) myocardial
      perfusion reserve (MPR) at 1.5 Tesla has been shown to correlate to invasive
      evaluation of coronary artery disease (CAD) and to yield good inter-observer
      agreement. However, little is known about quantitative adenosine-perfusion CMR at
      3 Tesla and no data about inter-observer agreement is available. Aim of our study
      was to evaluate inter-observer agreement and to assess the diagnostic accuracy in
      comparison to quantitative coronary angiography (QCA). METHODS: Fifty-three
      patients referred for coronary x-ray angiography were previously examined in a 3
      Tesla whole-body scanner. Adenosine and rest perfusion CMR were acquired for the
      quantification of MPR in all segments. Two blinded and independent readers
      analyzed all images. QCA was performed in case of coronary stenosis. QCA data was
      used to assess diagnostic accuracy of the MPR measurements. RESULTS: Inter
      observer agreement was high for all myocardial perfusion territories (rho = 0.92
      for LAD, rho = 0.93 for CX and RCA perfused segments). Compared to QCA receiver
      operating characteristics yielded an area under the curve of 0.78 and 0.73 for
      RCA, 0.66 and 0.69 for LAD, and 0.52 and 0.53 for LCX perfused territories.
      CONCLUSIONS: Inter-observer agreement of MPR quantification at 3 Tesla CMR is
      very high for all myocardial segments. Diagnostic accuracy in comparison to QCA
      yields good values for the RCA and LAD perfused territories, but moderate values
      for the posterior LCX perfused myocardial segments.

PMID- 23537062
TI  - Xenotropic MLV envelope proteins induce tumor cells to secrete factors that
      promote the formation of immature blood vessels.
AB  - BACKGROUND: Xenotropic Murine leukemia virus-Related Virus (XMRV) is a gamma
      retrovirus initially reported to be present within familial human prostate tumors
      and the blood of patients with chronic fatigue syndrome. Subsequent studies
      however were unable to replicate these findings, and there is now compelling
      evidence that the virus evolved through rare retroviral recombination events in
      human tumor cell lines established through murine xenograft experiments. There is
      also no direct evidence that XMRV infection has any functional effects that
      contribute to tumor pathogenesis. RESULTS: Herein we describe an additional
      xenotropic MLV, "B4rv", found in a cell line derived from xenograft experiments
      with the human prostate cancer LNCaP cell line. When injected subcutaneously in
      nude mice, LNCaP cells infected with XMRV or B4rv formed larger tumors that were
      highly hemorrhagic and displayed poor pericyte/smooth muscle cell (SMC)
      investment, markers of increased metastatic potential. Conditioned media derived
      from XMRV- or B4rv-infected LNCaPs, but not an amphotropic MLV control virus
      infected LNCaPs, profoundly decreased expression of marker genes in cultured SMC,
      consistent with inhibition of SMC differentiation/maturation. Similar effects
      were seen with a chimeric virus of the amphotropic MLV control virus containing
      the XMRV env gene, but not with an XMRV chimeric virus containing the amphotropic
      MLV env gene. UV-inactivated XMRV and pseudovirions that were pseudotyped with
      XMRV envelope protein also produce conditioned media that down-regulated SMC
      marker gene expression in vitro. CONCLUSIONS: Together these results indicate
      that xenotropic MLV envelope proteins are sufficient to induce the production of
      factors by tumor cells that suppress vascular SMC differentiation, providing
      evidence for a novel mechanism by which xenotropic MLVs might alter tumor
      pathogenesis by disrupting tumor vascular maturation. Although it is highly
      unlikely that either XMRV or B4Rv themselves infect humans and are pathogenic,
      the results suggest that xenograft approaches commonly used in the study of human
      cancer promote the evolution of novel retroviruses with pathogenic properties.

PMID- 23537064
TI  - A supratentorial primitive neuroectodermal tumor presenting with intracranial
      hemorrhage in a 42-year-old man: a case report and review of the literature.
AB  - INTRODUCTION: We report on a very rare case of a supratentorial primitive
      neuroectodermal tumor in an adult, which presented with intracerebral hemorrhage,
      and review the relevant medical literature. CASE PRESENTATION: A 42-year-old
      Caucasian man complained of a sudden headache and nausea-vomiting. The patient
      rapidly deteriorated to coma. An emergency computed tomography scan showed an
      extensive intraparenchymal hemorrhage that caused significant mass effect and
      tonsilar herniation. During surgery, an increased intracranial pressure was
      recorded and extensive bilateral decompressive craniectomies were performed. A
      cherry-like intraparenchymal lesion was found in his right frontal lobe and
      resected. The patient died in the intensive care unit after approximately 48
      hours. The resected lesion was identified as a central nervous system primitive
      neuroectodermal tumor. CONCLUSION: Supratentorial primitive neuroectodermal
      tumors must be considered in the differential diagnosis of space-occupying
      lesions in adults. Spontaneous supratentorial hemorrhage due to primitive
      neuroectodermal tumors is an extremely rare but potentially lethal event.

PMID- 23537063
TI  - Eudesmanolides from Wedelia trilobata (L.) Hitchc. as potential inducers of plant
      systemic acquired resistance.
AB  - Ten eudesmanolides (1-10) including five new ones (1-4 and 6) were isolated from
      the whole plant of Wedelia trilobata (L.) Hitchc., a notoriously invasive weed in
      South China. As main constituents of W. trilobata, eight of these eudesmanolides
      were tested for their antitobacco mosaic virus (TMV) activities by the
      conventional half-leaf and leaf-disk method along with Western blot analysis. All
      of the tested compounds, at 10 MUg/mL, showed strong antiviral activities in the
      pretreated tobacco plants with inhibition rates ranging from 46.7% to 76.5%,
      significantly higher than that of the positive control, ningnanmycin (13.5%).
      Their potential of inducing systemic acquired resistance (SAR) was also
      evaluated, and compounds 1 and 8 showed excellent induction activities.
      Furthermore, it was found that different concentrations of compound 1 promoted
      phenylalanine ammonia-lyase (PAL) activity in tobacco plants. To our knowledge,
      this is the first report that eudesmanolides could induce resistance in tobacco
      plants against the viral pathogen TMV. 

PMID- 23537065
TI  - X-ray structural information of GPCRs in drug design: what are the limitations
      and where do we go?
AB  - INTRODUCTION: In 2007, the X-ray structural determination of non-rhodopsin G
      Protein coupled receptors (GPCRs), considered the most extensively targeted
      protein class for marketed drugs, commenced. With the relatively rapid
      availability of additional structures, an assessment of the progression made is
      needed in addition to the assessment of the understandings gleaned, deployment
      successes and forthcoming prospects. AREAS COVERED: The author reviews the
      approaches and tools that have made it possible to determine the three
      dimensional structures of GPCRs using X-ray crystallography. Furthermore, the
      author describes the methods suited for crystallization of membrane bound GPCR
      proteins including the lipidic cubic phase and various protein modification
      approaches. The author also provides highlights, from the literature, of the
      structures determined to date including targets solved, the nature of the content
      provided (such as selectivity, activating vs. inactivating determinants) and how
      these structural features relate to drug design strategies. EXPERT OPINION: The
      GPCR X-ray structures that have been so far determined have yielded significant
      information. This has presented dramatic evidence concerning their ability to
      impact the discovery of compounds through their action as traditional,
      orthosteric modulators. It is, however, noted that more challenging design
      strategies, such as identifying biased agonists and the use of sites remote from
      the orthosteric site for allosteric modulation, are still in their infancy.

PMID- 23537066
TI  - Differences in impact of long term caregiving for mentally ill older adults on
      the daily life of informal caregivers: a qualitative study.
AB  - BACKGROUND: Owing to the policy of extramuralization of care in most Western
      countries older people with severe mental illness have to rely more and more on
      informal caregivers for daily care. Caregivers themselves are often aged, and
      although caregiving implies an impact on daily life that exceeds the boundaries
      of usual informal care, the impact differs across caregivers. Some caregivers
      seem to suffer more than others, and the differences cannot be fully understood
      by factors currently known to exacerbate the burden of caregiving. In order to
      help caregivers reduce the impact of caregiving it is important to gain a deeper
      understanding of factors influencing the burden and its impact on the caregiver's
      life. With this in mind, the aim of the study is to explore and understand
      differences in the impact of long-term caregiving on the quality of life of
      caregivers who look after older adults with severe mental illness. METHODS: A
      qualitative, associative, inductive strategy and continuous simultaneous coding
      were used to interpret the data of 19 semi-structured interviews. RESULTS: We
      identified an underlying psychological factor "perceived freedom of choice" which
      explains the gross differences in impact, leading to a definition of two main
      types of caregivers. Depending on how people perceive freedom of choice to
      provide care, the consequences of caregiving can be characterized as a process of
      gain (type 1) or loss (type 2). Four influential factors deepen the impact of
      caregiving for the type 2 caregivers, and two subtypes are identified for this
      category. Consequences of caregiving are most readily seen in a deteriorating
      quality of the relationship with the care recipient and in the psychosocial well
      being of the caregiver. CONCLUSIONS: The concept of freedom of choice adds to our
      understanding of the differences and explains the variation in impact on the
      caregivers' life. The type 1 caregiver generally experiences gain whereas type 2
      generally experiences loss, which puts the latter group typically at risk of
      becoming overloaded. Whether people perceive that they have freedom of choice in
      caregiving is an important consideration in evaluating the type of intervention
      needed to support caregivers.

PMID- 23537067
TI  - Comparing potential early caries assessment methods for teledentistry.
AB  - BACKGROUND: Optical caries detection has the potential to be incorporated in
      telehealth medicine for preventive dental screening. The objective of this study
      was to evaluate and compare visible and near infrared detection methods for
      identifying early non-cavitated ex vivo occlusal demineralization. METHODS: Six
      blinded examiners were used to compare the accuracy of the following three
      examinations in detecting occlusal demineralization: Midwest Caries ID (MID),
      visual photographic examination (CAM) and Cross Polarization Optical Coherence
      Tomography (CP-OCT). For each diagnostic method, two examiners assessed the
      extracted tooth samples 1-2 weeks apart. Teeth were then sectioned and lesion
      depth was confirmed (n = 42) by a blinded histological examination using a glycol
      based caries indicator dye. The sensitivity (Sen), specificity (Sp), Intraclass
      Correlation Coefficient (ICC), and Area under the Receiver Operator Curve (AUC)
      were calculated. RESULTS: For detecting any demineralization versus sound pit and
      fissure enamel, the mean Sen/Sp found was 46.9/85.0 for MID, 80.5/52.5 for CAM,
      and 83.4/45.0 for CP-OCT. For detecting non-cavitated demineralization that
      progressed into the dentin, the mean Sen/Sp found was 17.3/88.0 for MID,
      48.0/57.8 for CAM, and 44.2/72.7 for CP-OCT. AUC values were statistically
      significant (P < 0.05) in three out of four examiner assessments when MID and CP
      OCT were used to detect any demineralization. AUC values were significant for a
      single CAM examination. When assessing deeper non-cavitated lesions, none of the
      assessment methods were able to yield AUC values that were significantly
      different than a random 'coin flip' test. When examining reliability, MID
      demonstrated the highest ICC score (0.83) and CP-OCT had the lowest (0.49).
      CONCLUSION: Although MID and CP-OCT were useful in detecting the presence of
      demineralization, examiners were not able to utilize these devices to adequately
      assess the depth of the demineralization. This study found that MID and CP-OCT
      did not have markedly superior diagnostic values from simple CAM assessment for
      use in teledentistry.

PMID- 23537069
TI  - New insights on the reorganization of gene transcription in Pseudomonas putida
      KT2440 at elevated pressure.
AB  - BACKGROUND: Elevated pressure, elevated oxygen tension (DOT) and elevated carbon
      dioxide tension (DCT) are readily encountered at the bottom of large industrial
      bioreactors and during bioprocesses where pressure is applied for enhancing the
      oxygen transfer. Yet information about their effect on bacteria and on the gene
      expression thereof is scarce. To shed light on the cellular functions affected by
      these specific environmental conditions, the transcriptome of Pseudomonas putida
      KT2440, a bacterium of great relevance for the production of medium-chain-length
      polyhydroxyalkanoates, was thoroughly investigated using DNA microarrays.
      RESULTS: Very well defined chemostat cultivations were carried out with P. putida
      to produce high quality RNA samples and ensure that differential gene expression
      was caused exclusively by changes of pressure, DOT and/or DCT. Cellular stress
      was detected at 7 bar and elevated DCT in the form of heat shock and oxidative
      stress-like responses, and indicators of cell envelope perturbations were
      identified as well.Globally, gene transcription was not considerably altered when
      DOT was increased from 40 +/- 5 to 235 +/- 20% at 7 bar and elevated DCT.
      Nevertheless, differential transcription was observed for a few genes linked to
      iron-sulfur cluster assembly, terminal oxidases, glutamate metabolism and
      arginine deiminase pathway, which shows their particular sensitivity to
      variations of DOT. CONCLUSIONS: This study provides a comprehensive overview on
      the changes occurring in the transcriptome of P. putida upon mild variations of
      pressure, DOT and DCT. Interestingly, whereas the changes of gene transcription
      were widespread, the cell physiology was hardly affected, which illustrates how
      efficient reorganization of the gene transcription is for dealing with
      environmental changes that may otherwise be harmful. Several particularly
      sensitive cellular functions were identified, which will certainly contribute to
      the understanding of the mechanisms involved in stress sensing/response and to
      finding ways of enhancing the stress tolerance of microorganisms.

PMID- 23537070
TI  - Construction of a plant-transformation-competent BIBAC library and genome
      sequence analysis of polyploid Upland cotton (Gossypium hirsutum L.).
AB  - BACKGROUND: Cotton, one of the world's leading crops, is important to the world's
      textile and energy industries, and is a model species for studies of plant
      polyploidization, cellulose biosynthesis and cell wall biogenesis. Here, we
      report the construction of a plant-transformation-competent binary bacterial
      artificial chromosome (BIBAC) library and comparative genome sequence analysis of
      polyploid Upland cotton (Gossypium hirsutum L.) with one of its diploid putative
      progenitor species, G. raimondii Ulbr. RESULTS: We constructed the cotton BIBAC
      library in a vector competent for high-molecular-weight DNA transformation in
      different plant species through either Agrobacterium or particle bombardment. The
      library contains 76,800 clones with an average insert size of 135 kb, providing
      an approximate 99% probability of obtaining at least one positive clone from the
      library using a single-copy probe. The quality and utility of the library were
      verified by identifying BIBACs containing genes important for fiber development,
      fiber cellulose biosynthesis, seed fatty acid metabolism, cotton-nematode
      interaction, and bacterial blight resistance. In order to gain an insight into
      the Upland cotton genome and its relationship with G. raimondii, we sequenced
      nearly 10,000 BIBAC ends (BESs) randomly selected from the library, generating
      approximately one BES for every 250 kb along the Upland cotton genome. The
      retroelement Gypsy/DIRS1 family predominates in the Upland cotton genome,
      accounting for over 77% of all transposable elements. From the BESs, we
      identified 1,269 simple sequence repeats (SSRs), of which 1,006 were new, thus
      providing additional markers for cotton genome research. Surprisingly,
      comparative sequence analysis showed that Upland cotton is much more diverged
      from G. raimondii at the genomic sequence level than expected. There seems to be
      no significant difference between the relationships of the Upland cotton D- and A
      subgenomes with the G. raimondii genome, even though G. raimondii contains a D
      genome (D5). CONCLUSIONS: The library represents the first BIBAC library in
      cotton and related species, thus providing tools useful for integrative physical
      mapping, large-scale genome sequencing and large-scale functional analysis of the
      Upland cotton genome. Comparative sequence analysis provides insights into the
      Upland cotton genome, and a possible mechanism underlying the divergence and
      evolution of polyploid Upland cotton from its diploid putative progenitor
      species, G. raimondii.

PMID- 23537068
TI  - The western painted turtle genome, a model for the evolution of extreme
      physiological adaptations in a slowly evolving lineage.
AB  - BACKGROUND: We describe the genome of the western painted turtle, Chrysemys picta
      bellii, one of the most widespread, abundant, and well-studied turtles. We place
      the genome into a comparative evolutionary context, and focus on genomic features
      associated with tooth loss, immune function, longevity, sex differentiation and
      determination, and the species' physiological capacities to withstand extreme
      anoxia and tissue freezing. RESULTS: Our phylogenetic analyses confirm that
      turtles are the sister group to living archosaurs, and demonstrate an
      extraordinarily slow rate of sequence evolution in the painted turtle. The
      ability of the painted turtle to withstand complete anoxia and partial freezing
      appears to be associated with common vertebrate gene networks, and we identify
      candidate genes for future functional analyses. Tooth loss shares a common
      pattern of pseudogenization and degradation of tooth-specific genes with birds,
      although the rate of accumulation of mutations is much slower in the painted
      turtle. Genes associated with sex differentiation generally reflect phylogeny
      rather than convergence in sex determination functionality. Among gene families
      that demonstrate exceptional expansions or show signatures of strong natural
      selection, immune function and musculoskeletal patterning genes are consistently
      over-represented. CONCLUSIONS: Our comparative genomic analyses indicate that
      common vertebrate regulatory networks, some of which have analogs in human
      diseases, are often involved in the western painted turtle's extraordinary
      physiological capacities. As these regulatory pathways are analyzed at the
      functional level, the painted turtle may offer important insights into the
      management of a number of human health disorders.

PMID- 23537071
TI  - Association between UCP2 A55V polymorphism and risk of cardiovascular events in
      patients with multi-vessel coronary arterial disease.
AB  - BACKGROUND: UCP2 (uncoupling protein 2) plays an important role in cardiovascular
      diseases and recent studies have suggested that the A55V polymorphism can cause
      UCP2 dysfunction. The main aim was to investigate the association of A55V
      polymorphism with cardiovascular events in a group of 611 patients enrolled in
      the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial
      comparing treatments for patients with coronary artery disease and preserved left
      ventricular function. METHODS: The participants of the MASS II were genotyped for
      the A55V polymorphism using allele-specific PCR assay. Survival curves were
      calculated with the Kaplan-Meier method and evaluated with the log-rank
      statistic. The relationship between baseline variables and the composite end
      point of cardiac death, acute myocardial infarction (AMI), refractory angina
      requiring revascularization and cerebrovascular accident were assessed using a
      Cox proportional hazards survival model. RESULTS: There were no significant
      differences for baseline variables according genotypes. After 2 years of follow
      up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI
      (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and
      combined events (p=0.037) as compared with patients carrying other genotypes.
      This association was not evident in normoglycemic patients. CONCLUSIONS: These
      findings support the hypothesis that A55V polymorphism is associated with UCP2
      functional alterations that increase the risk of cardiovascular events in
      patients with previous coronary artery disease and dysglycemia.

PMID- 23537072
TI  - Feasibility of 1H-high resolution-magic angle spinning NMR spectroscopy in the
      analysis of viscous cosmetic and pharmaceutical formulations.
AB  - The feasibility of (1)H-High Resolution-Magic Angle Spinning (HR-MAS) nuclear
      magnetic resonance (NMR) spectroscopy for the direct analysis of viscous cosmetic
      and pharmaceutical formulations such as creams, gels, and pastes is presented.
      Three examples are described: (i) the detection of chitosan in toothpaste, (ii)
      the analysis of dexamethasone acetate (DMA) in a cream, and (iii) the analysis of
      the local anesthetics, lidocaine and prilocaine, in a gel and a cream. All active
      components could be directly detected in their original commercial formulations
      without the need for laborious sample preparation steps. In addition, the
      possibility for HR-MAS-based quantifications and the analysis of dynamic
      properties of active components in different formulations applying HR-MAS
      diffusion-ordered NMR spectroscopy are shown.

PMID- 23537073
TI  - Mean platelet volume could be possible biomarker in early diagnosis and
      monitoring of gastric cancer.
AB  - Gastric cancer is the fourth most frequent cancer and the second cause of cancer
      related deaths worldwide. The early diagnosis of gastric cancer is fundamental in
      decreasing the mortality rates. It has been shown that MPV level is a sign of
      inflammation in hepatocellular carcinoma and pancreatic adenocarcinoma. The aim
      of this study is to examine whether MPV would be a useful inflammatory marker for
      differentiating gastric cancer patients from healthy controls. Thirty-one gastric
      cancer patients and 31 age-sexes matched healthy subjects included into the
      study. Patients with hypertension, hematological and renal disease, heart
      failure, chronic infection, hepatic disorder and other cancer were excluded from
      the study. MPV level was significantly higher in pre-operative gastric cancer
      patients compared to healthy subjects (8.31 fL vs. 7.85; p: 0.007). ROC analysis
      suggested 8.25 fL as the cut-off value for MPV (AUC: 0.717, sensitivity: 61%,
      specificity: 81%). Surgical tumor resection resulted in a significant decrease in
      MPV level (8.31 fL vs. 7.55 fL; p: 0.001). No significant difference was found in
      MPV level between the post-operative group and control subjects. We did not find
      statistically significant difference between MPV and TNM stages. In conclusion,
      changes in MPV values may be used as an easily available biomarker for monitoring
      the healthy patients for GC risk and may prompt physicians to make an early
      diagnosis of GC.

PMID- 23537074
TI  - Adverse events associated with botulinum toxin injection: a multidepartment,
      retrospective study of 5310 treatments administered to 1819 patients.
AB  - BACKGROUND: The injection of botulinum toxin is now commonly used for many
      therapeutic and cosmetic purposes but because of its increased use more adverse
      events are being reported. OBJECTIVE: To retrospectively evaluate and analyze the
      safety of botulinum toxin injections in terms of purpose and the type of toxin
      administered. MATERIALS AND METHODS: Data were collected on 1819 patients who
      underwent a total of 5310 treatments between 2005 and 2011 at a single tertiary
      medical center. Information on the dosage, treatment purpose, type of botulinum
      toxin, and any adverse events associated with these treatments were collected and
      analyzed. The generalized estimating equation (GEE) with the logistic link
      function was used to estimate the overall frequencies of adverse events. A
      multivariable GEE with the logistic link function was used to identify the
      factors associated with adverse events. RESULTS: Among the 5310 botulinum toxin
      treatments in our study cohort, 2258 of which (42.5%) were used to treat
      hemifacial spasm, 184 adverse events (3.73%) were recorded, 114 (2.26%) muscle
      related, and 71 (1.47%) muscle-unrelated. The highest number of adverse events
      (8.29%) was associated with the treatment of blepharospasm and the lowest (1.07%)
      with masseter hyperplasia. By multivariate analysis, the odds ratio for females
      was 1.577 (95% confidence interval [CI] = 1.052-2.364; p = 0.027) and for the
      dose was 1.006 (95% CI = 1.002-1.010; p = 0.005). When compared with upper face
      wrinkles, the odds ratio was 2.510 (95% CI = 1.400-4.499; p = 0.002) for
      blepharospasm, 0.375 (95% CI = 0.202-0.695; p = 0.002) for cervical dystonia, and
      0.114 (95% CI: 0.015-0.862; p = 0.035) for masseter hyperplasia. CONCLUSION: When
      injecting botulinum toxin for cosmetic purposes, practitioners should be
      cautious, especially when targeting the areas around the eyes, as these
      treatments are prone to cause adverse events.

PMID- 23537075
TI  - Oxygen attachment on alkanethiolate SAMs induced by low-energy electron
      irradiation.
AB  - Reactions of (18)O2 with self-assembled monolayer (SAM) films of 1-dodecanethiol,
      1-octadecanethiol, 1-butanethiol, and benzyl mercaptan chemisorbed on gold were
      studied by the electron stimulated desorption (ESD) of anionic fragments over the
      incident electron energy range 2-20 eV. Dosing the SAMs with (18)O2 at 50 K
      results in the ESD of (18)O(-) and (18)OH(-). Electron irradiation of samples
      prior to (18)O2 deposition demonstrates that intensity of subsequent (18)O(-) and
      (18)OH(-) desorption signals increase with electron fluence and that in the
      absence of electron preirradiation, no (18)O(-) and (18)OH(-) ESD signals are
      observed, since oxygen is unable to bind to the SAMs. A minimum incident electron
      energy of 6-7 eV is required to initiate the binding of (18)O2 to the SAMs. O2
      binding is proposed to proceed by the formation of CHx-1(*) radicals via resonant
      dissociative electron attachment and nonresonant C-H dissociation processes. The
      weaker signals of (18)O(-) and (18)OH(-) from short-chain SAMs are related to the
      latter's resistance to electron-induced damage, due to the charge-image dipole
      quenching and electron delocalization. Comparison between the present results and
      those for DNA oligonucleotides self-assembled on Au (Mirsaleh-Kohan, N. et al. J.
      Chem. Phys. 2012, 136, 235104) indicates that the oxygen binding mechanism is
      common to both systems.

PMID- 23537076
TI  - Red blood cell distribution and survival in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) contributes significantly to mortality
      in chronic obstructive pulmonary disease (COPD). Red blood cell distribution
      width (RDW), an automated measure of red blood cell size heterogeneity that is
      largely overlooked, is a newly recognized mortality marker in patients with
      established CVD. It is unknown whether RDW is associated with mortality in COPD
      patients. AIMS: To study the prognostic value of RDW in patients with COPD and to
      compare the value of this measurement with cardiac, respiratory, and
      hemotological status. METHOD: We performed retrospective analyses of 270 patients
      stable with COPD who were admitted to our hospital between January 2007 and
      December 2009. Demographic, clinical, echocardiographic, and laboratory
      characteristics were registered and recorded COPD deaths were registered as
      outcomes. RESULTS: In the overall patients, the RDW level had a mean value of
      15.1 +/- 2.4. RDW was positively correlated with C-reactive protein (CRP) (p =
      0.008, r = 0.21), right ventricular dysfunction (RVD) (p < 0.001, r = 0.25), and
      pulmonary arterial hypertension (PAH) (p = 0.03, r = 0.14). Variables (p < 0.1)
      included in the univariate survival analysis were forced expiratory volume in 1
      second (FEV1% predicted), RDW levels, age, PaCO2, albumine and CRP levels,
      presence of CVD, presence of anemia, presence of RVD, and presence of PAH.
      Subsequent multivariate analysis suggested that RDW levels (1.12; 95% CI, 1.01 to
      1.24; p = 0.01), and presence of RVD (2.6; 95% CI, 1.19 to 5.8; p = 0.01) were
      independently related to mortality. CONCLUSION: Elevated RDW levels were
      associated with increased mortality risk in stable COPD patients.

PMID- 23537077
TI  - Cellular actions of nesfatin-1 on hypothalamic and medullary neurons.
AB  - The present review summarizes the current understanding of the neuronal
      activation patterns induced by nesfatin-1 in both the hypothalamus and the
      brainstem, as well as the physiological outcomes caused by the activation of
      these neuronal populations. Studies using cFos measurements, Ca(2+) imaging
      techniques, electrophysiological recordings, and microinjections have led to the
      identification of the paraventricular nucleus, arcuate nucleus, lateral and
      ventromedial hypothalamic areas, as well as medullary centers such as the nucleus
      of the solitary tract and dorsal motor nucleus of the vagus as targets of central
      nesfatin-1 actions on food intake, cardiovascular function, stress responses, and
      glucose homeostasis. 

PMID- 23537078
TI  - Possible role of NUCB2/nesfatin-1 in adipogenesis.
AB  - NUCB2 and its proteolytically cleaved product nesfatin-1 were initially
      identified as hypothalamic neuroproteins that inhibit food intake, via a leptin
      independent pathway. Since then recent studies have found NUCB2/nesfatin-1 to be
      expressed both centrally, as well as in peripheral tissues. The recent
      implementation of novel experimental approaches has produced a large body of
      evidence implicating NUCB2/nesfatin-1 in a diverse range of biological functions
      and in the modulation of food intake, energy homeostasis and metabolism. In this
      review, we discuss the discovery of NUCB2 and its proteolytic product nesfatin-1,
      and its expression in both central and peripheral tissues. In addition we shed
      light on the most recent discoveries supporting the role for NUCB2/nesfatin-1 in
      peripheral tissues and its association with metabolic alterations. Moreover, we
      highlight the importance of NUCB2 and nesfatin-1 in adipose tissue, its
      regulation of adipogenesis and obesity-associated metabolic diseases. 

PMID- 23537079
TI  - Central and peripheral expression and distribution of NUCB2/nesfatin-1.
AB  - Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2). The antibody
      against nesfatin-1 recognizes both full length of NUCB2 and nesfatin-1, thus the
      immunolabeling represents NUCB2/nesfatin-1. It has been found that NUCB2/nesfatin
      1 is widely distributed in the rodent central nervous system. The
      immunoreactivity is more intensive in the brain autonomic centers that regulate
      feeding, neuroendocrine and cardiovascular functions, such as the hypothalamic
      paraventricular nucleus, supraoptic nucleus, lateral hypothalamic area, Edinger
      Westphal nucleus, locus coeruleus, dorsal vagal complex and medullary raphe
      nuclei. In neurons, NUCB2/nesfatin-1 is located in the soma and primary
      dendrites, not in nerve fibers. NUCB2/nesfatin-1 is co-localized with several
      neurotransmitters involved in regulation of food intake, autonomic and
      neuroendocrine functions, including oxytocin, vasopressin, neuropeptide Y,
      cocaine- and amphetamine-regulated transcript, proopiomelanocortin, alpha
      melanocyte-stimulating hormone, melanin-concentrating hormone, leptin, mammalian
      target of rapamycin, urocortin-1, corticotropin-releasing factor and serotonin.
      In the periphery, NUCB2/nesfatin-1 is located mainly in the pituitary, gastric
      mucosa where it coexists with ghrelin, and pancreatic endocrine cells containing
      insulin. Nesfatin-1 is detectable in the cerebrospinal fluid of rats.
      NUCB2/nesfatin-1 is measurable in the plasma, and altered under different
      conditions in rodents and humans, such as immune challenge, high fat diet and
      exercise, anorexia nervosa, anxiety and depression. Anatomical data suggest that
      nesfatin-1 is a unique neuroendocrine peptide that may be involved in regulation
      of homeostasis. 

PMID- 23537080
TI  - Emerging roles of NUCB2/nesfatin-1 in the metabolic control of reproduction.
AB  - Nesfatin-1, derived from the precursor NEFA/nucleobindin2 (NUCB2), was initially
      identified as a feeding-suppressing neuropeptide, acting at central (mainly,
      hypothalamic) levels in a leptin-independent manner. However, recent experimental
      evidence strongly suggests that, rather than being a simple anorectic
      hypothalamic signal, nesfatin-1 operates at different tissues as an integral
      regulator of energy homeostasis and closely related neuroendocrine functions. On
      the latter, growing, albeit as yet fragmentary, evidence has pointed out recently
      that NUCB2/ nesfatin-1 is involved in the regulation of different aspects of
      reproductive maturation and function, by acting probably at different levels of
      the hypothalamic-pituitary-gonadal (HPG) axis. As documented by rodent studies,
      the reproductive facet of nesfatin-1 likely includes (i) a permissive role in
      (female) pubertal maturation, (ii) stimulatory effects on the gonadotropic axis,
      whose magnitude, in terms of LH responses, varies depending on the maturational
      stage and probably the sex and species, and (iii) direct expression and actions
      in the gonads. These features, together with the proven expression of
      NUCB2/nesfatin-1 in tissues with essential roles in the metabolic control of
      reproduction, such as the hypothalamus, adipose and pancreas, support a putative
      role of nesfatin-1 as neurohormonal signal linking body metabolic status, puberty
      and fertility. Curiously enough, although its reproductive dimension seems to be
      conserved in non-mammalian vertebrates, recent studies in goldfish have surfaced
      predominant inhibitory actions of nesfatin-1 at different levels of the HPG axis
      in fish. These findings illustrate our as yet limited understanding of this
      aspect of nesfatin-1 physiology, whose relevance in the joint control of
      metabolism and reproduction in health and disease warrants further investigation.

PMID- 23537081
TI  - Discovery of nesfatin-1 and overview of biological actions and new developments.
AB  - Obesity arises from an impairment of energy homeostasis, which essentially
      involves the balance of food intake and energy dissipation. Some secreted
      molecules in the hypothalamus have become the focus of recent attention for their
      important roles in the regulation of food intake. One such molecule, nesfatin-1,
      is a novel molecule originally expressed in the hypothalamic nuclei of the brain,
      which exerts its satiety function in conjunction with other molecules, including
      oxytocin and pro-opiomelanocortin (POMC). Nesfatin-1 is processed from its
      precursor, DNA binding/EF-hand/acidic protein (NEFA)/nucleobindin 2 (NUCB2), and
      its mRNA is unexpectedly stabilized by troglitazone, a ligand for peroxisome
      proliferator-activated receptor gamma (PPARgamma). Subsequent analyses and
      observations have demonstrated that nesfatin-1 is also located in brain nuclei
      outside the hypothalamus and in peripheral tissues, and that nesfatin-1 neurons
      in the brain receive several signals. These findings imply that nesfatin-1 is an
      endogenous molecule important for the regulation of not only food intake but also
      other physiological functions. We discuss what is currently known about nesfatin
      1, including new developments in our understanding of its distribution,
      regulation, and biological function. 

PMID- 23537082
TI  - Role of NUCB2/nesfatin-1 as a possible biomarker.
AB  - Nesfatin-1, discovered by Oh-I and his coworkers in 2006, is a multi-functional
      peptide hormone with an approximate MW of 9.8 kDa and a half-life of 23.5
      minutes. This peptide is found in three different forms, nesfatin-1, nesfatin-2
      and nesfatin-3, all three of which are formed from the precursor NUCB2 by
      proteolytic processing. The 30-amino acid middle segment of nesfatin-1 (M30) is
      responsible for limiting food intake, while the exact physiological role of
      nesfatin-2 and nesfatin-3 is unknown. This review will focus on nesfatin-1 in
      relation with tissue and fluid distribution, considerations for its analysis in
      body fluids, and its potential as a biomarker for some diseases. 

PMID- 23537083
TI  - Phylogenetic aspects of nucleobindin-2/nesfatin-1.
AB  - Nesfatin-1 is an eighty two amino acid, naturally occurring multifunctional
      protein encoded in the precursor nucleobindin-2 (NUCB2). A comparison of
      sequences indicates that NUCB2 is present in a number of animals, from hydra to
      humans. The 30 amino acid mid-segment of nesfatin-1 is considered to be the
      bioactive core of the protein, and this region displays the highest identity
      among nesfatin-1 sequences reported thus far. Similar to the sequence
      relationships observed, the tissue-specific expression and biological actions of
      nesfatin-1 also appear to be highly conserved across species. For example, brain
      is a major tissue abundantly expressing nesfatin- 1 in several species. It has
      been shown that various key regions of the rat, mouse and goldfish brain, which
      are involved in the regulation of feeding and metabolism express nesfatin-1.
      Exogenous administration of nesfatin-1 results in a decrease in the food intake
      of rats, mice and goldfish. In addition, nesfatin-1 has been shown to regulate a
      number of other physiological processes including hormone secretion from the
      pancreatic islets and pituitary gland, stress and behavior. While nesfatin-1
      research still remains an emerging area in physiology, the literature available
      thus far clearly shows that nesfatin-1 is an important regulator of homeostasis
      in animals. 

PMID- 23537084
TI  - Nesfatin-1; implication in stress and stress-associated anxiety and depression.
AB  - Nesfatin-1, derived from an 82-amino-acid peptide precursor protein nucleobindin
      2 (NUCB2), is a highly conserved peptide across mammalian species. Initial
      functional and neuroanatomical studies on NUCB2/nesfatin-1 in the central nervous
      system have supported a role for NUCB2/nesfatin-1 as a novel satiety molecule. In
      recent years, however, it has become apparent that this neuropeptide is involved
      in various other processes, one of which is the stress response. Stress
      associated activation of NUCB2/nesfatin-1 neurons, together with nesfatin-1's
      central actions in the brain, is indicative of its significance in the stress
      adaptation response. Interestingly, increasing body of evidence implicates also
      NUCB2/nesfatin-1 in various forms of stress-associated psychopathologies, such as
      anxiety and depression. In this review, we will outline evidence that has
      significantly broadened our understanding of the biological significance of
      NUCB2/nesfatin-1 far beyond to be only a hypothalamic peptide with potent
      anorexigenic actions. NUCB2/nesfatin-1 neurons in the brain seem to emerge as
      novel, integral regulators of the stress adaptation response. 

PMID- 23537085
TI  - Role of NUCB2/nesfatin-1 in glucose control: diverse functions in islets,
      adipocytes and brain.
AB  - The novel satiety factor nesfatin-1 and its precursor NUCB2 are the neuropeptides
      widely expressed in the central nervous system. Nesfatin-1/NUCB2 is also
      localized in peripheral tissues and regulates the glucose and energy metabolism
      on multiple processes. Nesfatin-1 potentiates both insulin release from
      pancreatic beta-cells and insulin action in liver, contributing to energy
      storage. Furthermore, nesfatin-1/NUCB2 regulates adipocyte differentiation. The
      polymorphism of the NUCB2 gene is associated with obesity. Thus, nesfatin-
      1/NUCB2 plays a role in integrating feeding, glucose homeostasis, and energy
      storage/expenditure. Dysfunction of expression, secretion and/or action of
      nesfatin-1/NUCB2 might be involved in the type 2 diabetes, obesity and metabolic
      syndrome. Nesfatin-1/NUCB2 and its regulatory processes may provide novel targets
      for treating associated diseases of the metabolic syndrome. Here, we review the
      by now published studies on nesfatin-1/NUCB2 localization and action in islets
      and discuss the physiological and pathophysiological roles of the nesfatin
      1/NUCB2 in glucose and energy metabolism. 

PMID- 23537086
TI  - Regulation of gastric nesfatin-1/NUCB2.
AB  - Originally identified in the hypothalamus as a satiety factor, recent studies
      provide evidence that nefatin-1/NUCB2 is a gutbrain peptide with a broader array
      of actions. Detection of abundant nesfatin-1/NUCB2 in gastric X/A like endocrine
      cells, which also produce the orexigenic hormone ghrelin, indicates that gastric
      mucosa may be one of the predominant sources of nesfatin-1/NUCB2. Functional
      studies have revealed significant effects of nefatin-1 on inhibition of feeding
      behavior and on glucose homeostasis. These metabolic functions make nesfatin
      1/NUCB2 a novel candidate for treatment of obesity and diabetes. However,
      deficiencies in our understanding of nesfatin-1/NUCB2 receptor pose a significant
      hurdle for therapies that target its action. Defining novel pathways to alter the
      production of nesfatin-1/NUCB2 would shift therapeutic focus to gastric targets.
      A necessary precondition is improved understanding of the mechanisms by which
      nesfatin-1/NUCB2 is synthesized and secreted by gastric X/A like cells. Recent
      studies provide evidence that mTOR is a critical regulatory molecule in these
      endocrine cells and that its activity is linked to the production of ghrelin and
      nesfatin- 1/NUCB2. These findings suggest that gastric mTOR is involved in the
      regulation of food intake and overall energy metabolism through modulation of
      ghrelin and nesfatin-1/NUCB2. In this review, we first summarize current advances
      in the relationship between organism energy status and nesfatin-1/NUCB2 levels,
      and then discuss the novel finding on mTOR as the gastric fuel sensor and its
      role in the regulation of nesfatin-1/NUCB2 expression. 

PMID- 23537087
TI  - Cardiovascular and antidipsogenic effects of nesfatin-1.
AB  - Nesfatin-1, derived from the nucleobindin-2 gene product, is expressed in neurons
      located in brain centers known to be important in the central regulation of both
      cardiovascular function and fluid and electrolyte homeostasis. In fact the
      peptide colocalizes in those neurons with an impressive list of neuropeptides and
      neurotransmitters known to be important in the regulation of thirst, appetite and
      central autonomic control. We and others have demonstrated potent sympatho
      stimulatory actions of nesfatin-1 in brain and the potential physiologic
      relevance of those effects. In addition, although nesfatin-1 was originally
      described as a peptide with potent anorexigenic actions in brain, effects
      corroborated by several groups, it is possible that the anorexigenic actions of
      nesfatin-1 are secondary to a primary action to reduce thirst. Progress in
      unraveling the importance of endogenous nesfatin-1 in cardiovascular function, or
      fluid and electrolyte homeostasis, has been limited due to the to date
      unavailability of nesfatin-1 antagonists and the fact that the receptor for
      nesfatin-1 remains unidentified. 

PMID- 23537089
TI  - New Developments On NUBC2/Nesfatin-1.

PMID- 23537088
TI  - Role of brain NUCB2/nesfatin-1 in the regulation of food intake.
AB  - Nesfatin-1 was recently identified in the rat brain as a potential post
      translational processing product derived from nucleobindin2 (NUCB2). The first
      biological action identified for nesfatin-1 was the reduction of nocturnal food
      intake in rats. The anorexigenic effect of nesfatin-1 was corroborated by several
      independent laboratories and is now established as a physiological action of this
      peptide based on the regulation of brain NUCB2/nesfatin-1 under different
      metabolic conditions and the stimulation of food intake and body weight when
      endogenous brain NUCB2/nesfatin-1 is blocked. Nesfatin-1 shows extensive co
      localization with various other, predominantly food intake inhibitory,
      hypothalamic peptides including corticotropin-releasing factor (CRF), oxytocin,
      cholecystokinin, proopiomelanocortin, -alphamelanocyte stimulating hormone (alpha
      MSH), thyrotropin-releasing hormone (TRH), the orexigenic neuropeptide Y and
      brain biogenic amines, histamine, serotonin, and catecholamines. The food intake
      suppressing effect of centrally injected nesfatin-1 has been established so far
      to involve several downstream mechanisms including H1, CRF2, TRH, oxytocin as
      well as melanocortin-3/4 receptor signaling pathways. This intricate embedding of
      NUCB2/nesfatin-1 in central food intake regulatory pathways recruited during the
      dark phase corresponding to the eating period in rodents, unlike the orexigenic
      response to a fast, points towards a role for nesfatin-1 in modulating the
      nocturnal food intake. Although our knowledge on the regulation and effects of
      NUCB2/nesfatin-1 as a new anorexic peptide markedly increased during the past
      five years, several important gaps of knowledge remain to be filled in the near
      future such as the regulation of NUCB2 processing and nesfatin-1 release as well
      as the identification, localization and regulation of the nesfatin-1 receptor. 

PMID- 23537090
TI  - Interaction and release of catechin from anhydride maleic-grafted polypropylene
      films.
AB  - In this paper, investigations were carried out on catechin-loaded maleic
      anhydride (MAH)-modified polypropylenes (PP). Two maleic-modified polypropylenes
      (PPMAH) with different maleic concentrations have been blended with PP and
      catechin to obtain composites of improved catechin retention with the aim of
      studying the possible interactions between these grafted polymers with
      antioxidants, and a secondary interest in developing an active antioxidant
      packaging. Composite physicochemical properties were measured by thermal analysis
      (thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and
      oxidation induction time (OIT)) and infrared spectroscopy studies. Catechin
      release profiles into food simulants were obtained by HPLC-PDA-QqQ, following
      European legislation. Antiradical activity of composites was analyzed by the ABTS
      and DPPH method. The formation of intermolecular hydrogen bonds between catechin
      and functionalized PP has been confirmed by Fourier transform infrared (FTIR)
      studies. Besides, a small fraction of ester bonds, formed as a result of a
      chemical reaction between a fraction of the hydrolyzed anhydride and the catechin
      hydroxyl groups, is not discarded. OIT results also showed an increase in
      antioxidant effectiveness caused by the presence of catechin- and maleic-modified
      PPMAH in the blend formulations. Incorporation of MAH-grafted PP increased
      substantially the retention rate of catechin, being dependent on the MAH content
      of the grafted polypropylene. The described interactions between catechin and
      maleic groups, together with changes in PP morphology in comparison with
      reference PP explained lower antioxidant release. Besides formulation,
      antioxidant release was dependent on the type of food, the temperature, and the
      time.

PMID- 23537092
TI  - Palliative care need and management in the acute hospital setting: a census of
      one New Zealand Hospital.
AB  - BACKGROUND: Improving palliative care management in acute hospital settings has
      been identified as a priority internationally. The aim of this study was to
      establish the proportion of inpatients within one acute hospital in New Zealand
      who meet prognostic criteria for palliative care need and explore key aspects of
      their management. METHODS: A prospective survey of adult hospital inpatients (n =
      501) was undertaken. Case notes were examined for evidence that the patient might
      be in their last year of life according to Gold Standards Framework (GSF)
      prognostic indicator criteria. For patients who met GSF criteria, clinical and
      socio-demographic information were recorded. RESULTS: Ninety-nine inpatients met
      GSF criteria, representing 19.8% of the total census population. The patients'
      average age was 70 years; 47% had a primary diagnosis of cancer. Two thirds had
      died within 6 months of their admission. Seventy-eight of the 99 cases
      demonstrated evidence that a palliative approach to care had been adopted;
      however documentation of discussion about goals of care was very limited and only
      one patient had evidence of an advance care plan. CONCLUSION: One fifth of
      hospital inpatients met criteria for palliative care need, the majority of whom
      were aged >70 years. Whilst over three quarters were concluded to be receiving
      care in line with a palliative care approach, very little documented evidence of
      discussion with patients and families regarding end of life issues was evident.
      Future research needs to explore how best to support 'generalist' palliative care
      providers in initiating, and appropriately recording, such discussions.

PMID- 23537091
TI  - Impact of genetic variation and geographic distribution of porcine reproductive
      and respiratory syndrome virus on infectivity and pig growth.
AB  - BACKGROUND: The porcine reproductive and respiratory syndrome (PRRS) is a
      devastating disease for the pig industry. In this study, we analysed the genetic
      variability of PRRS virus (PRRSV) as well as the relationship between the genetic
      variability, the geographical and temporal distribution of the PRRSV strains.
      Moreover, we investigated the association between the glycosylation patterns in
      PRRSV sequences and pigs growth. RESULTS: The data highlight that PRRSV strains
      evolve rapidly on individual farms, and temporal evolution of PRRSV is an
      important factor of genetic variability. Analysis of glycosylation sites in the
      glycoprotein 5 (GP5) ectodomain revealed that PRRSV isolates had seven
      combinations of putative N-linked glycosylation sites of which the N37/46/53
      sites was found in 79% of the sequences. No significant relationship was found
      between the genetic variation of the PRRSV strains and the geographic distance. A
      significant relationship was found between the genetic variation and time of
      sampling when farm was considered as a factor in the analysis. Furthermore, the
      commercial semen from artificial insemination centres was not a source of PRRS
      transmission.The PRRSV having the glycosylation site at position N46 (N46+) were
      observed to have higher burden on pigs and accordingly the corresponding infected
      pigs had lower average daily gain (ADG) compared with those infected with PRRSV
      lacking the glycosylation at N46 (N46-) position site. This study showed that the
      number of piglets by litter infected by PRRSV was lower for the Landrace breed
      than for the other studied breeds (Large White, Duroc and Pietrain). CONCLUSIONS:
      The PRRSV genetic variability which is determined by a local and temporal
      evolution at the farm level could be considered in a perspective of prevention.
      Moreover, the association between the PRRSV glycosylation patterns and its
      virulence could be of interest for vaccine development. The differences of
      resistance to PRRSV infections among pig breeds might open new horizons for the
      genetic selection of robustness against PRRSV infection.

PMID- 23537093
TI  - Rapid ungated myocardial perfusion cardiovascular magnetic resonance: preliminary
      diagnostic accuracy.
AB  - BACKGROUND: Myocardial perfusion cardiovascular magnetic resonance (CMR) is a
      well-established method for detection of ischemic heart disease. However, ECG
      gating problems can result in image degradation and non-diagnostic scans,
      particularly in patients with arrhythmias. METHODS: A turboFLASH saturation
      recovery pulse sequence was used without any ECG triggering. One saturation pulse
      followed by 4-5 slices of undersampled radial k-space images was acquired
      rapidly, on the order of 40-50 msec per image. The acquisition of the set of 4-5
      slices was continuously repeated approximately 4 times per second. An iterative
      constrained reconstruction method was used to reconstruct the ungated images. The
      ungated perfusion images were post-processed into three different sets of images
      (ungated, self-gated to near systole, and self-gated to near diastole). To test
      the ungated approach and compare the different processing methods, 8 patients
      scheduled for coronary angiography underwent stress and rest perfusion imaging
      with the ungated acquisition. Six patients had a history of atrial fibrillation
      (AF). Three blinded readers assessed image quality and presence/absence of
      disease. RESULTS: All 8 subjects successfully completed the perfusion CMR
      protocol and 7/8 underwent coronary angiography. Three patients were in atrial
      fibrillation during CMR. Overall, the CMR images were of high quality as assessed
      by the three readers. There was little difference in image quality between
      patients in AF compared to those in sinus rhythm (3.6+/-0.7 vs. 3.3+/-0.5).
      Stress/rest perfusion imaging showed normal perfusion in 4 patients, fixed
      perfusion defects in 2 patients, and reversible perfusion defects in 2 patients,
      corresponding with angiographic results. Pooled results from the independent
      readers gave a sensitivity of 0.92 (CI 0.65-0.99) and specificity of 0.92 (CI
      0.65-0.99) for the detection of coronary artery disease using ungated perfusion
      imaging. The same sensitivity, and a specificity of 1 (CI 0.76-1), was achieved
      when the images were self-gated after acquisition into near systole or near
      diastole. CONCLUSIONS: Ungated radial dynamic perfusion CMR can give high quality
      imaging in patients in sinus rhythm and during atrial fibrillation. In this small
      cohort, high diagnostic accuracy was possible with this rapid perfusion imaging
      sequence. An ungated approach simplifies the acquisition and could expand the
      role of perfusion CMR to include patients with arrhythmia and those with gating
      problems.

PMID- 23537094
TI  - Flavonoids of Dikamali: A phytochemical reinvestigation.
AB  - Eleven known flavonoids (1-11) were isolated from Dikamali, the gum resin of
      Gardenia lucida. Three of them, desmethylnobiletin, pectolinarigenin and
      xanthomicrol, are a new report from this source. Nuclear magnetic resonance (NMR)
      data are being given for all the isolates. For two of them, viz., 3',4'
      dimethoxywogonin and 4'-hydroxywogonin, such data have not been reported in
      literature. Furthermore, correct NMR data are being provided for gardenin C as
      the data reported in literature were found to be incorrect. 

PMID- 23537095
TI  - Comparative psychometric analyses of the SCL-90-R and its short versions in
      patients with affective disorders.
AB  - BACKGROUND: Despite the widespread application of Symptom Checklist 90-R (SCL-90
      R), its psychometric weaknesses have repeatedly been noted. This study aimed to
      comparatively assess the psychometric properties of the SCL-90-R scales and the
      scales of its short versions Brief Symptom Inventory (BSI), Symptom Checklist-27
      (SCL-27), Brief Symptom Inventory-18 (BSI-18), Symptom Checklist-14 (SCL-14), and
      Symptom Checklist short version-9 (SCL-K-9) in patients with affective disorders.
      METHODS: The data of 2,727 patients within the main treatment group of affective
      disorders were assessed according to the DSM-IV. Patients completed the SCL-90-R
      and Beck Depression Inventory (BDI). RESULTS: There were no significant
      differences regarding the internal consistency of the SCL-90-R scales and the
      scales of the short versions. The dimensional structure was only supported for
      the short versions BSI-18, SCL-14 and SCL-K-9. The assessment of convergent
      validity revealed high correlations. With regard to the discriminant validity,
      there were medium correlations. With regard to the sensitivity of change, no
      significant differences between the scales were found. CONCLUSIONS: In summary,
      the scales of the short versions show mostly satisfactory psychometric properties
      in comparison to the scales of the SCL-90-R. The results support the application
      of the short versions as screening instruments, especially the BSI-18, and more
      economic variants of the SCL-90-R covering a wide range of psychopathological
      symptoms.

PMID- 23537096
TI  - Exploring drug delivery systems for treating osteoporosis.
AB  - INTRODUCTION: Osteoporosis (OP) is a major disease in elderly people; its
      complications and prevalence are rapidly increasing worldwide. It is associated
      with high fragility fracture mainly of hip, wrist and spine. With the rising
      lifespan worldwide, the number of hip fractures throughout globe will rise from
      1.66 million in 1990 to 6.26 million by 2050. So there is a major problem in our
      society related to the bone diseases which needs to be addressed. AREAS COVERED:
      This review gives knowledge about OP, its symptoms and problems associated with
      the existing therapies. It gives idea about various drug delivery systems for
      bone targeting. This review also gives a comprehensive compilation of the various
      in vitro and in vivo studies conducted till date and US FDA approved drugs for
      the treatment of OP. EXPERT OPINION: Various drug delivery systems reduce the
      adverse effects of drugs and increase the availability of drugs to the target
      site mainly bones. Active researches are going on to improve the OP treatment,
      whose high prevalence and considerable functional and socioeconomic impact will
      raise formidable challenges in the near future. We should work on different
      targets rather than conventional therapies which will improve the overall
      treatment strategies.

PMID- 23537097
TI  - Genome sequence of ground tit Pseudopodoces humilis and its adaptation to high
      altitude.
AB  - BACKGROUND: The mechanism of high-altitude adaptation has been studied in certain
      mammals. However, in avian species like the ground tit Pseudopodoces humilis, the
      adaptation mechanism remains unclear. The phylogeny of the ground tit is also
      controversial. RESULTS: Using next generation sequencing technology, we generated
      and assembled a draft genome sequence of the ground tit. The assembly contained
      1.04 Gb of sequence that covered 95.4% of the whole genome and had higher N50
      values, at the level of both scaffolds and contigs, than other sequenced avian
      genomes. About 1.7 million SNPs were detected, 16,998 protein-coding genes were
      predicted and 7% of the genome was identified as repeat sequences. Comparisons
      between the ground tit genome and other avian genomes revealed a conserved genome
      structure and confirmed the phylogeny of ground tit as not belonging to the
      Corvidae family. Gene family expansion and positively selected gene analysis
      revealed genes that were related to cardiac function. Our findings contribute to
      our understanding of the adaptation of this species to extreme environmental
      living conditions. CONCLUSIONS: Our data and analysis contribute to the study of
      avian evolutionary history and provide new insights into the adaptation
      mechanisms to extreme conditions in animals.

PMID- 23537099
TI  - Infratentorial benign cystic meningioma mimicking a hemangioblastoma
      radiologically and a pilocytic astrocytoma intraoperatively: a case report.
AB  - INTRODUCTION: Cystic meningiomas are rare variants of meningiomas; they can pose
      a radiological diagnostic dilemma. CASE PRESENTATION: We present a rare case of a
      30-year-old Chinese woman with a histopathological diagnosis of infratentorial
      cystic meningioma (World Health Organization Grade 1) in which the features in
      imaging modalities were suggestive of a hemangioblastoma. Intraoperatively,
      however, the gross macroscopic features were more in keeping with a pilocytic
      astrocytoma. CONCLUSION: In benign cystic meningiomas, particularly the
      infratentorial variety, radiological findings utilizing the various imaging
      modalities and intraoperative impressions may not be reflective of or in keeping
      with the final histopathological diagnosis.

PMID- 23537098
TI  - Identification of diverse full-length endogenous betaretroviruses in megabats and
      microbats.
AB  - BACKGROUND: Betaretroviruses infect a wide range of species including primates,
      rodents, ruminants, and marsupials. They exist in both endogenous and exogenous
      forms and are implicated in animal diseases such as lung cancer in sheep, and in
      human disease, with members of the human endogenous retrovirus-K (HERV-K) group
      of endogenous betaretroviruses (betaERVs) associated with human cancers and
      autoimmune diseases. To improve our understanding of betaretroviruses in an
      evolutionarily distinct host species, we characterized betaERVs present in the
      genomes and transcriptomes of mega- and microbats, which are an important
      reservoir of emerging viruses. RESULTS: A diverse range of full-length betaERVs
      were discovered in mega- and microbat genomes and transcriptomes including the
      first identified intact endogenous retrovirus in a bat. Our analysis revealed
      that the genus Betaretrovirus can be divided into eight distinct sub-groups with
      evidence of cross-species transmission. Betaretroviruses are revealed to be a
      complex retrovirus group, within which one sub-group has evolved from complex to
      simple genomic organization through the acquisition of an env gene from the genus
      Gammaretrovirus. Molecular dating suggests that bats have contended with
      betaretroviral infections for over 30 million years. CONCLUSIONS: Our study
      reveals that a diverse range of betaretroviruses have circulated in bats for most
      of their evolutionary history, and cluster with extant betaretroviruses of
      divergent mammalian lineages suggesting that their distribution may be largely
      unrestricted by host species barriers. The presence of betaERVs with the ability
      to transcribe active viral elements in a major animal reservoir for viral
      pathogens has potential implications for public health.

PMID- 23537100
TI  - The novel mTOR inhibitor CCI-779 (temsirolimus) induces antiproliferative effects
      through inhibition of mTOR in Bel-7402 liver cancer cells.
AB  - BACKGROUND: Liver cancer is one of the most frequent cancers in the world.
      Targeted therapy of cancer with specific inhibitors is developing and has shown
      promising antitumor efficacy. CCI-779 (temsirolimus), a specific inhibitor of
      mTOR (mammalian target of rapamycin), can block the mTOR signaling pathway. Here,
      we systematically examined the expression of mTOR and its downstream targets in
      liver cancer cells and normal liver cells, then investigated inhibitory effects
      of CCI-779 on mTOR signaling pathway and its role in regulating liver cancer cell
      growth. METHODS: The expression of mTOR and its downstream targets in Bel-7402
      liver cancer cells and HL-7702 normal liver cells were examined by western blot.
      The mTOR specific inhibitor (CCI-779) was used to treat Bel-7402 cells to
      identify its effects on Bel-7402 cell growth and activity of mTOR signaling
      pathway in vitro. Cell viability tests were performed after the treatment of CCI
      779. Western blot was applied to assess the changes of mTOR pathway and flow
      cytometry was used to analyze cell cycle of Bel-7402 cells after the treatment of
      CCI-779. RESULTS: mTOR, p70S6K, S6, and 4EBP1 were overexpressed in Bel-7402
      cells compared with HL-7702 cells. Bel-7402 cells were sensitive to CCI-779. The
      survival rate of the cells treated with CCI-779 over 0.312 MUM was significantly
      different compared with that of control (P < 0.05). CCI-779 inhibited the
      phosphorylation of mTOR (Ser2448), p70S6K (Thr389), S6 (Ser240/244), and 4EBP1
      (Thr37/46) in different grades and the expressions of p70S6K, S6, and 4EBP1. As a
      result, CCI-779 induced a dose-dependent decrease in cell proliferation, G1/S
      arrest and damage of cell shape. CONCLUSIONS: Taken together, these data showed
      that CCI-779 can inhibit mTOR signaling and proliferation in Bel-7402 liver
      cancer cells in vitro. It offers a therapeutic intervention through inhibition of
      mTOR as a potential strategy for liver cancer.

PMID- 23537101
TI  - How does the solvation unveil AtO+ reactivity?
AB  - The AtO(+) molecular ion, a potential precursor for the synthesis of
      radiotherapeutic agents in nuclear medicine, readily reacts in aqueous solution
      with organic and inorganic compounds, but at first glance, these reactions must
      be hindered by spin restriction quantum rules. Using relativistic quantum
      calculations, coupled to implicit solvation models, on the most stable
      AtO(+)(H2O)6 clusters, we demonstrate that specific interactions with water
      molecules of the first solvation shell induce a spin change for the AtO(+) ground
      state, from a spin state of triplet character in the gas phase to a Kramers
      restricted closed-shell configuration in solution. This peculiarity allows
      rationalization of the AtO(+) reactivity with closed-shell species in aqueous
      solution and may explain the differences in astatine reactivity observed in
      (211)At production protocols based on "wet" and "dry" processes.

PMID- 23537102
TI  - Development of a novel method for the determination of aqueous inorganic 129I
      speciation.
AB  - The objective of this research was to develop a method suitable for the
      determination of aqueous concentrations of radioactive iodine as I2, I(-), and
      IO3(-). As one of the primary risk-drivers and contaminants of concern at nuclear
      waste repositories, the accurate determination of (129)I in aqueous systems is of
      significant concern. The redox-active nature of iodine makes its mobility and
      fate in the environment difficult to predict, thus underscoring the importance of
      species-specific determination of iodine concentrations. The developed method
      couples solid phase extraction with liquid scintillation counting, and
      scintillating anion exchange with a flow-cell detection system for a sequential
      measurement of each iodine species. Solid phase extraction disks were impregnated
      with polyvinylpyrrolidone for the selective extraction and stabilization of I2
      with subsequent analysis by liquid scintillation counting. Aqueous I(-) was
      concentrated and measured by a previously developed flow-cell system utilizing
      scintillating anion-exchange resin. A subsequent chemical reduction of IO3(-) to
      I(-) in the effluent was used to quantify IO3(-) by the same flow-cell system.
      Nearly quantitative results were found for standardized single-species samples of
      I2 (95%), I(-) (101%), and IO3(-) (91%), respectively, while consistent
      measurements were obtained for multispecies samples using the developed method
      and algorithm. 

PMID- 23537103
TI  - BATF regulates the development and function of IL-17 producing iNKT cells.
AB  - BACKGROUND: BATF plays important roles in the function of the immune system. Batf
      null mice are deficient in both CD4+ Th17 cells and T follicular helper cells and
      possess an intrinsic B cell defect that leads to the complete absence of class
      switched Ig. In this study, Tg mice overexpressing BATF in T cells were used
      together with Batf null mice to investigate how altering levels of BATF
      expression in T cells impacts the development and function of a recently
      characterized population of iNKT cells expressing IL-17 (iNKT-17). RESULTS: BATF
      has a direct impact on IL-17 expression by iNKT cells. However, in contrast to
      the Th17 lineage where BATF activates IL-17 expression and leads to the expansion
      of the lineage, BATF overexpression restricts overall iNKT cell numbers while
      skewing the compartment in vivo and in vitro toward an iNKT-17 phenotype.
      CONCLUSIONS: This work is the first to demonstrate that BATF joins RORgammat as
      the molecular signature for all IL-17 producing cells in vivo and identifies BATF
      as a component of the nuclear protein network that could be targeted to regulate
      IL-17-mediated disease. Interestingly, these studies also reveal that while the
      Il17a gene is a common target for BATF regulation in Th17 and iNKT-17 cells, this
      regulation is accompanied by opposite effects on the growth and expansion of
      these two cell lineages.

PMID- 23537104
TI  - Coagulation activation, depletion of platelet granules and endothelial integrity
      in case of uraemia and haemodialysis treatment.
AB  - BACKGROUND: During haemodialysis (HD) treatment, increase of platelet (PLT)
      activation and induction of procoagulant activity is demonstrated. Although the
      role of the endothelium and its direct interaction with coagulation and
      homeostasis is known, it is not elucidated how PLT activation markers and
      activation of coagulation coincide with markers of endothelial integrity during
      HD treatment. In the present study uraemia and HD induced changes, with
      particular emphasis on PLT granules depletion, activation of coagulation and
      endothelial integrity were investigated. METHODS: To detect depletion of PLT
      granules, peripheral blood slide smears were screened by light microscopy for
      qualitative evaluation of PLT granule containing cytoplasm, as indicated by its
      granules staining density. Activation of coagulation was investigated by
      establishement of thrombin-antithrombin (TAT) and fibrinogen concentrations. To
      evaluate endothelial integrity proendothelin (proET-1) plasma concentrations were
      established. RESULTS: Results of our study demonstrate that proET-1 plasma
      concentrations were obviously increased in the subjects' group with end-stage
      chronic kidney disease (CKD) and renal failure if compared with a group of
      apparently healthy subjects. The amount of depleted PLT granules was obviously
      increased in the subjects' group with end-stage CKD if compared with the group
      with renal failure. Mean plasma concentrations of TAT and fibrinogen revealed
      results within the reference range. CONCLUSIONS: It is demonstrated that uraemia
      is associated with endothelial damage and aberrations in PLT granules morphology
      in subjects with HD treatment. We hypothesize that increased proET-1
      concentrations reflect ongoing stress on endothelial cells amongst others due to
      uraemia. Biomarkers like proET-1 and aberrations in PLT granules morphology
      assist in the early detection of procoagulant activity of the endothelium.

PMID- 23537105
TI  - Assessing the specificity of autobiographical memory in individuals at a trait
      based vulnerability to bipolar disorder using a sentence completion task.
AB  - Overgeneral autobiographical memory recall has been associated with the diagnosis
      of bipolar disorder, but the role of overgenerality in the vulnerability to
      bipolar disorder remains under-researched. While a previous study suggested that
      high-risk individuals for bipolar disorder recall emotionally negative memories
      in specific detail, this is in contrast to memory recall patterns noted in
      bipolar samples. The Autobiographical Memory Test (AMT) used in previous non
      clinical studies has also been criticised for not being sensitive to
      overgenerality due to its repetition of specificity instructions and practice
      trials. The traditional AMT format may allow some individuals to override their
      trait-based tendencies to be overgeneral. The current study used a sentence
      completion task to assess memory specificity in groups of students at a low and
      high trait-based vulnerability for bipolar disorder. In contrast to previous
      research, high-risk individuals recalled fewer specific positive memories and
      greater numbers of overgeneral negative memories than low-risk individuals. These
      results support the notion that the vulnerability for bipolar disorder might be
      associated with similar recall biases as demonstrated in bipolar samples, and
      that the AMT might not be sufficiently sensitive to detect overgenerality in non
      clinical groups. The implications of these findings and directions for future
      research are discussed. 

PMID- 23537106
TI  - Verification of icephobic/anti-icing properties of a superhydrophobic surface.
AB  - Four aluminum surfaces with wettability varied from superhydrophilic to
      superhydrophobic were prepared by combining an etching and a coating process. The
      surface wettability was checked in terms of water contact angle (CA) and sliding
      angle (SA) under different humidity at -10  degrees C. High-speed photography was
      applied to study water droplet impact dynamics on these surfaces. It was found
      that single and successive water droplets could rebound on the superhydrophobic
      surface and roll off at a tilt angle larger than 30 degrees  under an extremely
      condensing weather condition (-10  degrees C and relative humidity of 85-90%). In
      addition, the superhydrophobic surface showed a strong icephobic property, the
      ice adhesion on this surface was only 13% of that on the superhydrophilic
      surface, though they had a similar nano/microtopological structure. Moreover,
      this superhydrophobic surface displayed an excellent durability of the icephobic
      property. The ice adhesion only increased to 20% and 16% of that on the
      superhydrophobic surface after the surface was undergone 20 icing/ice-breaking
      cycles and 40 icing/ice-melting cycles, respectively. Surface profile and XPS
      studies on these surfaces indicated a minor damage of the surface
      nano/microstructure and the coating layer upon these multiple ice-breaking and
      ice-melting processes. Therefore, this superhydrophobic surface could be a good
      candidate for icephobic applications.

PMID- 23537107
TI  - Mechanics of capillary forming of aligned carbon nanotube assemblies.
AB  - Elastocapillary self-assembly is emerging as a versatile technique to manufacture
      three-dimensional (3D) microstructures and complex surface textures from
      arrangements of micro- and nanoscale filaments. Understanding the mechanics of
      capillary self-assembly is essential to engineering of properties such as shape
      directed actuation, anisotropic wetting and adhesion, and mechanical energy
      transfer and dissipation. We study elastocapillary self-assembly (herein called
      "capillary forming") of carbon nanotube (CNT) microstructures, combining in situ
      optical imaging, micromechanical testing, and finite element modeling. By
      imaging, we identify sequential stages of liquid infiltration, evaporation, and
      solid shrinkage, whose kinetics relate to the size and shape of the CNT
      microstructure. We couple these observations with measurements of the orthotropic
      elastic moduli of CNT forests to understand how the dynamic of shrinkage of the
      vapor-liquid interface is coupled to the compression of the forest. We compare
      the kinetics of shrinkage to the rate of evporation from liquid droplets having
      the same size and geometry. Moreover, we show that the amount of shrinkage during
      evaporation is governed by the ability of the CNTs to slip against one another,
      which can be manipulated by the deposition of thin conformal coatings on the CNTs
      by atomic layer deposition (ALD). This insight is confirmed by finite element
      modeling of pairs of CNTs as corrugated beams in contact and highlights the
      coupled role of elasticity and friction in shrinkage and stability of nanoporous
      solids. Overall, this study shows that nanoscale porosity can be tailored via the
      filament density and adhesion at contact points, which is important to the
      development of lightweight multifunctional materials.

PMID- 23537108
TI  - Quality assurance in transnational higher education: a case study of the tropEd
      network.
AB  - INTRODUCTION: Transnational or cross-border higher education has rapidly expanded
      since the 1980s. Together with that expansion issues on quality assurance came to
      the forefront. This article aims to identify key issues regarding quality
      assurance of transnational higher education and discusses the quality assurance
      of the tropEd Network for International Health in Higher Education in relation to
      these key issues. METHODS: Literature review and review of documents. RESULTS:
      From the literature the following key issues regarding transnational quality
      assurance were identified and explored: comparability of quality assurance
      frameworks, true collaboration versus erosion of national education sovereignty,
      accreditation agencies and transparency. The tropEd network developed a
      transnational quality assurance framework for the network. The network accredits
      modules through a rigorous process which has been accepted by major stakeholders.
      This process was a participatory learning process and at the same time the
      process worked positive for the relations between the institutions. DISCUSSION:
      The development of the quality assurance framework and the process provides a
      potential example for others.

PMID- 23537109
TI  - CRAC: an integrated approach to the analysis of RNA-seq reads.
AB  - A large number of RNA-sequencing studies set out to predict mutations, splice
      junctions or fusion RNAs. We propose a method, CRAC, that integrates genomic
      locations and local coverage to enable such predictions to be made directly from
      RNA-seq read analysis. A k-mer profiling approach detects candidate mutations,
      indels and splice or chimeric junctions in each single read. CRAC increases
      precision compared with existing tools, reaching 99:5% for splice junctions,
      without losing sensitivity. Importantly, CRAC predictions improve with read
      length. In cancer libraries, CRAC recovered 74% of validated fusion RNAs and
      predicted novel recurrent chimeric junctions. CRAC is available at
      http://crac.gforge.inria.fr. 

PMID- 23537110
TI  - Capture of terrestrial-sized moons by gas giant planets.
AB  - Terrestrial moons with masses >0.1 M (symbol in text) possibly exist around
      extrasolar giant planets, and here we consider the energetics of how they might
      form. Binary-exchange capture can occur if a binary-terrestrial object (BTO) is
      tidally disrupted during a close encounter with a giant planet and one of the
      binary members is ejected while the other remains as a moon. Tidal disruption
      occurs readily in the deep gravity wells of giant planets; however, the large
      encounter velocities in the wells make binary exchange more difficult than for
      planets of lesser mass. In addition, successful capture favors massive binaries
      with large rotational velocities and small component mass ratios. Also, since the
      interaction tends to leave the captured moons on highly elliptical orbits,
      permanent capture is only possible around planets with sizable Hill spheres that
      are well separated from their host stars.

PMID- 23537111
TI  - Variability and homogeneity of cardiovascular magnetic resonance myocardial T2
      mapping in volunteers compared to patients with edema.
AB  - BACKGROUND: The aim of the study was to test the reproducibility and variability
      of myocardial T2 mapping in relation to sequence type and spatial orientation in
      a large group of healthy volunteers. For control T2 mapping was also applied in
      patients with true edema. Cardiovascular magnetic resonance (CMR) T2-mapping has
      potential for the detection and quantification of myocardial edema. Clinical
      experience is limited so far. The variability and potential pitfalls in broad
      application are unknown. METHODS: Healthy volunteers (n = 73, 35 +/- 13 years)
      and patients with edema (n = 28, 55 +/- 17 years) underwent CMR at 1.5 T. Steady
      state free precession (SSFP) cine loops and T2-weighted spin echo images were
      obtained. In patients, additionally late gadolinium enhancement images were
      acquired. We obtained T2 maps in midventricular short axis (SAX) and four-chamber
      view (4CV) based on images with T2 preparation times of 0, 24, 55 ms and compared
      fast low angle shot (FLASH) and SSFP readout. 10 volunteers were scanned twice on
      separate days. Two observers analysed segmental and global T2 per slice. RESULTS:
      In volunteers global myocardial T2 systematically differed depending on image
      orientation and sequence (FLASH 52 +/- 5 vs. SSFP 55 +/- 5 ms in SAX and 57 +/- 6
      vs. 59 +/- 6 ms in 4CV; p < 0.0001 for both). Anteroseptal and apical segments
      had higher T2 than inferior and basal segments (SAX: 59 +/- 6 vs. 48 +/- 5 ms for
      FLASH and 59 +/- 7 vs. 52 +/- 4 ms for SSFP; p < 0.0001 for both). 14 volunteers
      had segments with T2 >= 70 ms. Mean intraobserver variability was 1.07 +/- 1.03
      ms (r = 0.94); interobserver variability was 1.6 +/- 1.5 ms (r = 0.87). The
      coefficient of variation for repeated scans was 7.6% for SAX and 6.6% for 4CV.
      Mapping revealed focally increased T2 (73 +/- 9 vs. 51 +/- 3 ms in remote
      myocardium; p < 0.0001) in all patients with edema. CONCLUSIONS: Myocardial T2
      mapping is technically feasible and highly reproducible. It can detect focal
      edema and differentiate it from normal myocardium. Increased T2 was found in some
      volunteers most likely due to partial volume and residual motion.

PMID- 23537112
TI  - Inhaled alpha 1-antitrypsin: gauging patient interest in a new treatment.
AB  - BACKGROUND: Given the high cost of plasma derived intravenous alpha 1-antitrypsin
      (AAT), a more efficient method of delivery to the lungs is desirable. Inhaled AAT
      has been shown feasible for the treatment of alpha 1-antitrypsin deficiency
      (AATD) and is currently in clinical trials. To better understand patient
      preferences about possible inhaled AAT therapy, a survey was conducted to explore
      patient attitudes. METHODS: We conducted an email based survey of patients in the
      Alpha-1 Foundation Research Registry with AATD on intravenous AAT replacement.
      Respondents were asked to rate their interest in hypothetical nebulized or dry
      powder inhaled AAT. RESULTS: Respondents reported high levels of interest in both
      dried powder inhaler and nebulizer delivered inhaled AAT. The interest in dried
      powder inhaled was higher than interest in nebulized AAT (71% vs 64%, p =
      0.0001). The interest in dried powder inhaled AAT was particularly high in
      respondents currently on bronchodilator therapy (p = 0.0053). Patients were just
      as likely to use or not use the product if it required 20% more out of pocket
      cost. CONCLUSIONS: There is a high level of patient interest in the development
      of a commercially available inhaled AAT replacement product.

PMID- 23537113
TI  - In stationary regime, electron transfer rates in RTIL media are diffusion
      controlled: experimental evidence from pulse radiolysis study.
AB  - We report electron transfer (ET) process from the long-lived radical anions of
      pyrene and benzophenone to molecular acceptors, e.g., benzophenone and
      fluorenone, respectively, in two RTIL media, namely, [BMIM][PF6] and [BMIM][BF4],
      as well as a few other conventional organic solvents using the nanosecond pulse
      radiolysis technique. Decay of the donor radical anion and concomitant formation
      of the acceptor radical anion ensure a bimolecular ET process. The rate constants
      for the bimolecular ET process in both normal organic solvents and RTILs have
      been found to be nearly equal to diffusion controlled rate calculated for the
      corresponding solvent. For long-lived anions, having lifetimes longer than a few
      hundred nanoseconds, quenching occurs mainly in the stationary regime. In this
      regime, the ET rate is fully controlled by the rate of diffusion of the reactive
      species in those solvents. To the best of our knowledge, this is the first
      experimental evidence of the diffusion controlled ET process occurring in the
      stationary regime in RTIL media.

PMID- 23537115
TI  - Evaluation of Greek psychiatric reforms: methodological issues.
AB  - Over the last three decades significant efforts have been made in many European
      countries to move away from a mental health system dominated by institutional
      care towards one whereby the main emphasis is on providing care and support
      within the community. Although the time of starting the reforms, their pace, the
      political context, and the exact objectives varies substantially across Europe,
      practically all countries have been undergoing such major reforms aimed at
      establishing services in the community to replace institutional based care. Each
      country makes its own decisions about the necessary mental health services taking
      into account a range of factors including population needs, level of resources,
      flexibility and coordination of organizational structures, as well as local
      culture. These factors become an integral element of a national mental health
      policy and action plan, closely linked with national public health
      strategies.Greece has been modernizing an outdated mental health system, which
      was based on institutional care, over the last 20 years, by developing community
      based mental health care. This article describes the methodology used for the
      evaluation of the Psychargos programme of the mental health reforms in Greece.
      Various forms of community-based mental health services have been developed
      including supported living facilities, community mental health centres and
      employment opportunities.

PMID- 23537116
TI  - HIV/AIDS knowledge and uptake of HIV counselling and testing among undergraduate
      private university students in Accra, Ghana.
AB  - BACKGROUND: HIV Counselling and Testing (VCT) and knowledge about HIV are some
      key strategies in the prevention and control of HIV/AIDS in Ghana. However, HIV
      knowledge and utilization of VCT services among university students is low. The
      main objective was to determine the level of HIV/AIDS knowledge and to explore
      factors associated with the use HIV counselling and testing among private
      university students in Accra, Ghana. MATERIALS AND METHODS: A cross-sectional
      study was conducted using structured questionnaires among 324 conveniently
      selected students enrolled at a privately owned tertiary institution in Accra,
      Ghana. RESULTS: The respondents consisted of 56.2% males and 43.8% females aged
      17 - 37 years. The mean HIV/AIDS knowledge score of was 7.70. There was a
      significant difference in knowledge of HIV/AIDS by gender where female students
      had more knowledge about HIV/AIDS than males [t (322) = 2.40, p = 0.017]. The
      ANOVA results showed that there was a significant difference in HIV/AIDS
      knowledge according to the age groups [F (3, 321) = 6.26, p = 0. 0001] and
      marital status [F (3, 321) = 4.86, p = 0. 008] of the sample. Over half of the
      participants had not tested for HIV, although over 95% of them knew where to
      access counseling and testing services. The study also revealed a significant
      association between demographic variables, testing for HIV and intention to test
      in the future. Participants who were never married (single), aged 17 - 20 years
      and had knowledge of two routes of HIV transmission were more likely to have
      taken an HIV test. Males were more likely to take an HIV test in the future than
      females. Majority of the students receive HIV/AIDS information from both print
      and electronic media, but few of them received such information from parents.
      CONCLUSION: The students HIV knowledge was very good, yet HIV testing were low.
      Health education and HIV intervention programmes must not only provide accurate
      information, but must be made to help to equip private university students,
      especially females to test for HIV consistently.

PMID- 23537114
TI  - Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and
      menopause.
AB  - Understanding the biology of sex differences is integral to personalized
      medicine. Cardiovascular disease and cognitive decline are two related
      conditions, with distinct sex differences in morbidity and clinical
      manifestations, response to treatments, and mortality. Although mortality from
      all-cause cardiovascular diseases has declined in women over the past five years,
      due in part to increased educational campaigns regarding the recognition of
      symptoms and application of treatment guidelines, the mortality in women still
      exceeds that of men. The physiological basis for these differences requires
      further research, with particular attention to two physiological conditions which
      are unique to women and associated with hormonal changes: pregnancy and
      menopause. Both conditions have the potential to impact life-long cardiovascular
      risk, including cerebrovascular function and cognition in women. This review
      draws on epidemiological, translational, clinical, and basic science studies to
      assess the impact of hypertensive pregnancy disorders on cardiovascular disease
      and cognitive function later in life, and examines the effects of post-menopausal
      hormone treatments on cardiovascular risk and cognition in midlife women. We
      suggest that hypertensive pregnancy disorders and menopause activate vascular
      components, i.e., vascular endothelium and blood elements, including platelets
      and leukocytes, to release cell-membrane derived microvesicles that are potential
      mediators of changes in cerebral blood flow, and may ultimately affect cognition
      in women as they age. Research into specific sex differences for these disease
      processes with attention to an individual's sex chromosomal complement and
      hormonal status is important and timely.

PMID- 23537117
TI  - Physical activity and beverage consumption in preschoolers: focus groups with
      parents and teachers.
AB  - BACKGROUND: Qualitative research is a method in which new ideas and strategies
      can be discovered. This qualitative study aimed to investigate parents' and
      teachers' opinions on physical activity and beverage consumption of preschool
      children. Through separate, independent focus groups, they expressed their
      perceptions on children's current physical activity and beverage consumption
      levels, factors that influence and enhance these behaviours, and anticipated
      barriers to making changes. METHODS: Multi-cultural and multi-geographical focus
      groups were carried out in six European countries (Belgium, Bulgaria, Germany,
      Greece, Poland and Spain). In total, twenty-four focus groups with 122 parents
      and eighteen focus groups with 87 teachers were conducted between October 2010
      and January 2011. Based on a semi-structured interview guide, questions on
      preschoolers' physical activity (opinions on preschoolers' physical activity, how
      to increase physical activity, facilitators and barriers of physical activity)
      and beverage consumption (rules and policies, factors influencing promotion of
      healthy drinking, recommendations for future intervention development) were
      asked. The information was analyzed using qualitative data analysis software
      (NVivo8). RESULTS: The focus group results indicated misperceptions of caregivers
      on preschoolers' physical activity and beverage consumption levels. Caregivers
      perceived preschoolers as sufficiently active; they argue that children need to
      learn to sit still in preparation for primary school. At most preschools,
      children can drink only water. In some preschools sugar-sweetened beverages like
      chocolate milk or fruit juices, are also allowed. It was mentioned that sugar
      sweetened beverages can be healthy due to mineral and vitamin content, although
      according to parents their daily intake is limited. These opinions resulted in
      low perceived needs to change behaviours. CONCLUSIONS: Although previous research
      shows need of change in obesity-related behaviours, the participants in the
      current study didn't perceive such. The awareness of parents and teachers needs
      to be raised concerning their shared responsibility about healthy behaviours in
      preschoolers. Providing preschool teachers with ready-to-use classroom material
      will encourage them to change physical activity and beverage consumption, and to
      implement related activities in the classroom. Involvement in activities that
      their children perform at preschool will motivate parents to extend these
      behaviours to the home environment.

PMID- 23537119
TI  - Bilateral central pain sensitization in rats following a unilateral thalamic
      lesion may be treated with high doses of ketamine.
AB  - BACKGROUND: Central post-stroke pain is a neuropathic pain condition caused by a
      vascular lesion, of either ischemic or hemorrhagic origin, in the central nervous
      system and more precisely involving the spinothalamocortical pathway responsible
      for the transmission of painful sensations. Few animal models have been developed
      to study this problem. The objectives of this study were to evaluate different
      modalities of pain in a central neuropathic pain rat model and to assess the
      effects of ketamine administered at different doses. Animals were evaluated on
      the rotarod, Hargreaves, Von Frey and acetone tests. A very small hemorrhage was
      created by injecting a collagenase solution in the right ventral posterolateral
      thalamic nucleus. Following the establishment of the neuropathy, ketamine was
      evaluated as a therapeutic drug for this condition. RESULTS: Histopathological
      observations showed a well localized lesion with neuronal necrosis and
      astrocytosis following the collagenase injection that was localized within the
      VPL. No significant change in motor coordination was observed following surgery
      in either the saline or collagensae groups. In the collagenase group, a
      significant decrease in mechanical allodynia threshold was observed. A sporadic
      and transient cold allodynia was also noted. No thermal hyperalgesia was seen
      following the collagenase injection. Ketamine was then tested as a potential
      therapeutic drug. A significant decrease in motor coordination was seen only
      following the administration of 25 mg/kg of ketamine in both groups. An
      alleviation of mechanical allodynia was achieved only with the high ketamine
      dose. The minimal effective ketamine serum concentration (150 ng/mL) was only
      achieved in animals that received 25 mg/kg. CONCLUSIONS: An intrathalamic
      hemorrhage induced a bilateral mechanical allodynia in rats. Cold hyperalgesia
      was observed in 60% of these animals. Mechanical allodynia was alleviated with
      high doses of ketamine which corresponded with therapeutic plasmatic
      concentrations.

PMID- 23537120
TI  - A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)
      associated glomerulonephritis and concurrent membranous nephropathy.
AB  - BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated
      glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are
      very rare combination. Their causal relationship has been suggested, but not
      determined. CASE PRESENTATION: A 73-years-old male with 5-year history of
      proteinuria underwent an operation for his sigmoid colon cancer. Seven months
      later, he was referred to a nephrology division due to an exacerbating renal
      function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA
      in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative
      glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas,
      immunofluorescent staining documented granular deposition of immumoglobulin (Ig)
      G and C3 along the capillary wall and electron microscopy showed subepithelial
      deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent
      staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak
      positive IgG4 suggested the possibility of malignancy-associated MN. CONCLUSION:
      Combination of MPO-ANCA-GN and MN are rare. Although the causal relationship has
      been suggested in some cases, we should consider all the possibilities including
      idiopathic MN and secondary MN associated with malignancy, drug use or infection.

PMID- 23537118
TI  - Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency
      detection with regard to the safe clinical deployment of 8-aminoquinoline
      treatment regimens: a workshop report.
AB  - The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency is a crucial aspect in the current phases of malaria control and
      elimination, which will require the wider use of 8-aminoquinolines for both
      reducing Plasmodium falciparum transmission and achieving the radical cure of
      Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe
      haemolysis in G6PD-deficient individuals, potentially creating significant
      morbidity and undermining confidence in 8-aminoquinoline prescription. On the
      other hand, erring on the side of safety and excluding large numbers of people
      with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will
      diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity
      is the most direct, accessible, and reliable assessment of the phenotype and
      remains the gold standard for the diagnosis of patients who could be harmed by
      the administration of primaquine. Genotyping seems an unambiguous technique, but
      its use is limited by cost and the large range of recognized G6PD genotypes. A
      number of enzyme activity assays diagnose G6PD deficiency, but they require a
      cold chain, specialized equipment, and laboratory skills. These assays are
      impractical for care delivery where most patients with malaria live. Improvements
      to the diagnosis of G6PD deficiency are required for the broader and safer use of
      8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be
      safely used to kill gametocytes without testing. The discussions and conclusions
      of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge
      gaps in G6PD deficiency are reported here.

PMID- 23537121
TI  - Periodontal treatment reduces matrix metalloproteinase levels in localized
      aggressive periodontitis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are a family of host-derived
      proteinases reported to mediate multiple functions associated with periodontal
      breakdown and inflammation. High MMP levels in African-American children with
      localized aggressive periodontitis (LAgP) have been reported previously by the
      present authors. However, little is known about MMP reductions in gingival
      crevicular fluid (GCF) after therapy. This study aims to evaluate MMP levels in
      the GCF after treatment of LAgP and to correlate these levels with clinical
      response. METHODS: GCF samples were collected from 29 African-American
      individuals diagnosed with LAgP. GCF was collected from one diseased site
      (probing depth [PD] >4 mm, bleeding on probing [BOP], and clinical attachment
      level >= 2 mm) and one healthy site (PD <= 3 mm, no BOP) from each individual at
      baseline and 3 and 6 months after periodontal treatment, which consisted of full
      mouth scaling and root planing (SRP) and systemic antibiotics. The volume of GCF
      was controlled using a calibrated gingival fluid meter, and levels of MMP-1, MMP
      2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 were assessed using fluorometric kits.
      RESULTS: MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13 levels were reduced
      significantly up to 6 months, comparable to healthy sites at the same point.
      Significant correlations were noted between MMP-2, MMP-3, MMP-8, MMP-9, MMP-12,
      and MMP-13 levels and percentage of sites with PD >4 mm. MMP-3, MMP-12, and MMP
      13 levels also correlated with mean PD of affected sites. CONCLUSION: Treatment
      of LAgP with SRP and systemic antibiotics was effective in reducing local levels
      of specific MMPs in African-American individuals, which correlated positively
      with some clinical parameters.

PMID- 23537122
TI  - Mathematical modeling suggests that periodontitis behaves as a non-linear chaotic
      dynamical process.
AB  - BACKGROUND: This study aims to expand on a previously presented cellular automata
      model and further explore the non-linear dynamics of periodontitis. Additionally
      the authors investigated whether their mathematical model could predict the two
      known types of periodontitis, aggressive (AgP) and chronic periodontitis (CP).
      METHODS: The time evolution of periodontitis was modeled by an iterative
      function, based on the hypothesis that the host immune response level determines
      the rate of periodontitis progression. The chaotic properties of this function
      were investigated by direct iteration, and the model was validated by immunologic
      and clinical parameters derived from two clinical study populations. RESULTS:
      Periodontitis can be described as chaos with the level of the host immune
      response determining its progression rate; the dynamics of the proposed model
      suggest that by increasing the host immune response level, periodontitis
      progression rate decreases. Renormalization transformations show the presence of
      two overlapping zones of disease activity corresponding to AgP and CP. By k-means
      cluster analysis, immunologic parameters corroborated the findings of the
      renormalization transformations. Periodontitis progression rates are modeled to
      scale with a power law of 1.3, and the mean exponential speed of the system is
      found to be 1.85 (metric entropy); clinical datasets confirmed the mathematical
      estimates. CONCLUSIONS: This study introduces a mathematical model that
      identifies periodontitis as a non-linear chaotic process. It offers a
      quantitative assessment of the disease progression rate and identifies two zones
      of disease activity that correspond to the existing classification of
      periodontitis in the AgP and CP types.

PMID- 23537123
TI  - Intrabony defects, open-flap debridement, and decortication: a randomized
      clinical trial.
AB  - BACKGROUND: Intramarrow penetration (IMP) is often incorporated in regenerative
      periodontal surgical procedures. However, the actual benefits of adding IMP to
      such a procedure remain undocumented. The purpose of this randomized controlled
      trial was to investigate the contribution of IMP to the outcomes of open-flap
      debridement (OFD) treatment of intrabony defects. METHODS: Forty-two chronic
      periodontitis patients, each contributing a 2-wall, 3-wall, or combined 2- to 3
      wall intrabony defect, were treated. Sites were randomly assigned into one of two
      groups: control (OFD alone) or test (OFD + IMP). Papilla preservation flaps were
      raised, and defects were thoroughly debrided. In the control group, complete
      primary closure of flaps was ensured after debridement. In the test group, IMP
      was performed before flap closure, using a round bur to penetrate the cortical
      defect wall. Clinical and radiographic parameters were assessed at baseline and
      12 months after treatment. RESULTS: At baseline, there were no statistically
      significant differences between groups. At 12 months, both groups experienced
      significant improvements, in terms of probing depth reduction, clinical
      attachment level (CAL) gain, and bone level (clinical and radiographic). The test
      group experienced significantly greater clinical bone gain (3.07 +/- 1.74 mm) and
      prevalence of CAL gain >=2 mm (93% of sites) compared with the control group
      (1.76 +/- 2.71 mm, P <0.03; 62%, P = 0.024). The test treatment benefits were
      particularly evident in mandibular sites, in which OFD + IMP doubled the
      radiographic bone gain obtained by OFD alone. CONCLUSION: Addition of IMP to an
      OFD procedure used to treat intrabony defects results in statistically and
      clinically significant enhancement of both clinical and radiographic outcomes.

PMID- 23537124
TI  - Stimulatory effects of glucose and Porphyromonas gingivalis lipopolysaccharide on
      the secretion of inflammatory mediators from human macrophages.
AB  - BACKGROUND: Hyperglycemia is widely considered to be the causal link between
      diabetes mellitus (DM) and diabetic complications. The purpose of this study is
      to determine the effects of high glucose in the presence of lipopolysaccharide
      (LPS) purified from the periodontal pathogen Porphyromonas gingivalis on human
      macrophages. METHODS: Macrophages (U937) were treated with various concentrations
      of P. gingivalis-LPS under normal (5.5 mM) or high (25 mM) glucose conditions.
      Mitochondrial dehydrogenase activity was determined using the 3-[4,5
      dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide assay. The levels of
      inflammatory mediators secreted were determined using the enzyme-linked
      immunosorbent assay and the competitive enzyme immunoassay. The intracellular
      calcium chelator was used to examine whether the intracellular calcium was
      involved. Statistical differences were assessed using a one-way analysis of
      variance and Tukey multiple-comparison intervals with alpha = 0.05. RESULTS: High
      glucose condition enhanced the mitochondrial dehydrogenase activity in
      macrophages. P. gingivalis-LPS induced the secretion of interleukin (IL)-6, tumor
      necrosis factor (TNF)-alpha, and prostaglandin E(2) (PGE(2)) in a dose-dependent
      manner both in normal and high glucose conditions. The stimulatory effects by P.
      gingivalis-LPS were more evident when cells were cultured under high glucose
      conditions. Changes of intracellular calcium concentration were involved not only
      in high glucose-induced mitochondrial dehydrogenase activity but also in P.
      gingivalis-LPS-induced production of IL-6, TNF-alpha, or PGE(2), especially under
      the high glucose conditions. CONCLUSIONS: High glucose appeared to enhance the
      inflammatory response induced by the periodontal pathogen. The information
      generated may help to delineate the possible mechanisms by which hyperglycemia
      compromises the periodontal health of patients with DM.

PMID- 23537125
TI  - Coculture with endothelial cells enhances osteogenic differentiation of
      periodontal ligament stem cells via cyclooxygenase-2/prostaglandin E2/vascular
      endothelial growth factor signaling under hypoxia.
AB  - BACKGROUND: During periodontitis and orthodontic tooth movement, periodontal
      vasculature is severely impaired, leading to a hypoxic microenvironment of
      periodontal cells. However, the impact of hypoxia on periodontal cells is poorly
      defined. The present study investigates responses of cocultured endothelial cells
      (ECs) and periodontal ligament stem cells (PDLSCs) to hypoxia. METHODS:
      Osteogenic differentiation, molecular characterization, and various behaviors of
      PDLSCs and human umbilical venous ECs under hypoxia were assessed by quantitative
      real-time reverse-transcription polymerase chain reaction, Western blot, and
      enzyme-linked immunosorbent assay. Moreover, the effect of ECs on PDLSC
      osteogenic differentiation was tested using NS398 (cyclooxygenase 2 blocker),
      SU5416 (vascular endothelial growth factor [VEGF] receptor inhibitor), AH6809, L
      798106, and L-161982 (EP1/2/3/4 antagonists). RESULTS: First, hypoxia promoted
      osteogenic differentiation in PDLSCs and enhanced EC migration, whereas PD98059
      (extracellular signal-regulated protein kinase [ERK] inhibitor) blocked, and
      cocultured ECs further enhanced, hypoxia-induced osteogenic differentiation.
      Second, NS398 impaired EC migration and prostaglandin E2 (PGE2)/VEGF release,
      whereas cocultured PDLSCs and exogenous PGE2 partially reversed it. Third, NS398
      (pretreated ECs) decreased PGE2/VEGF concentrations. NS398-treated ECs and
      AH6809/SU5416-treated PDLSCs impaired cocultured EC-induced enhancement of PDLSC
      osteogenic differentiation. CONCLUSIONS: Hypoxia enhances ERK-mediated osteogenic
      differentiation in PDLSCs. Coculture with EC further augments PDLSC osteogenic
      differentiation via cyclooxygenase-2/PGE2/VEGF signaling.

PMID- 23537126
TI  - Relations between the functions of autobiographical memory and psychological
      wellbeing.
AB  - Researchers have proposed that autobiographical memory serves three basic
      functions in everyday life: self-definition, social connection, and directing
      behaviour (e.g., Bluck, Alea, Habermas, & Rubin, 2005). However, no research has
      examined relations between the functions of autobiographical memory and healthy
      functioning (i.e., psychological wellbeing). The present research examined the
      relations between the self, social, and directive functions of autobiographical
      memory and three factors of psychological wellbeing in single and recurring
      autobiographical memories. A total of 103 undergraduate students were recruited
      and provided ratings of each function for four autobiographical memories (two
      single, two recurring events). Results found that individuals who use their
      autobiographical memories to serve self, social, and directive functions reported
      higher levels of Purpose and Communion and Positive Relationships, and that these
      relations differ slightly by event type. 

PMID- 23537127
TI  - Stable isotope-assisted lipidomics combined with nontargeted isotopomer
      filtering, a tool to unravel the complex dynamics of lipid metabolism.
AB  - Investigations of complex metabolic mechanisms and networks have become a focus
      of research in the postgenomic area, thereby creating an increasing demand for
      sophisticated analytical approaches. One such tool is lipidomics analysis that
      provides, a detailed picture of the lipid composition of a system at a given
      time. Introducing stable isotopes into the studied system can additionally
      provide information on the synthesis, transformation and degradation of
      individual lipid species. However, capturing the entire dynamics of lipid
      networks is still a challenge. We developed and evaluated a novel strategy for
      the in-depth analysis of the dynamics of lipid metabolism with the capacity for
      high molecular specificity and network coverage. The general workflow consists of
      stable isotope-labeling experiments, ultrahigh-performance liquid chromatography
      (UHPLC)/high-resolution Orbitrap-mass spectrometry (MS) lipid profiling and data
      processing by a software tool for global isotopomer filtering and matching. As a
      proof of concept, this approach was applied to the network-wide mapping of
      dynamic lipid metabolism in primary human skeletal muscle cells cultured for 4,
      12, and 24 h with [U-(13)C]-palmitate. In the myocellular lipid extracts, 692
      isotopomers were detected that could be assigned to 203 labeled lipid species
      spanning 12 lipid (sub)classes. Interestingly, some lipid classes showed high
      turnover rates but stable total amounts while the amount of others increased in
      the course of palmitate treatment. The novel strategy presented here has the
      potential to open new detailed insights into the dynamics of lipid metabolism
      that may lead to a better understanding of physiological mechanisms and metabolic
      perturbations. 

PMID- 23537128
TI  - Chemical constituents derived from Drimys brasiliensis Miers (Winteraceae).
AB  - Phytochemical investigation on Drimys brasiliensis afforded the isolation and
      characterisation of four drimane sesquiterpenes: polygodial (1), warburganal (2),
      1-beta-(p-coumaroyloxy)polygodial (3) and 1-beta-(p-methoxycinnamoyl)polygodial
      (4), as well as four flavonoids: quercitrin (5), astilbin (6), isoastilbin (7)
      and neoastilbin (8). The structures were elucidated on the basis of their
      spectral data and compared with those reported in the literature. Compounds 2, 5
      8 have been reported to occur for the first time in D. brasiliensis, while
      compounds 5, 7 and 8 have been reported to occur for the first time in the genus
      Drimys. The chemotaxonomic significance of these compounds, mainly flavonoids 5-8
      in D. brasiliensis, was summarised. 

PMID- 23537129
TI  - Emotional intelligence and academic performance in first and final year medical
      students: a cross-sectional study.
AB  - BACKGROUND: Research on emotional intelligence (EI) suggests that it is
      associated with more pro-social behavior, better academic performance and
      improved empathy towards patients. In medical education and clinical practice, EI
      has been related to higher academic achievement and improved doctor-patient
      relationships. This study examined the effect of EI on academic performance in
      first- and final-year medical students in Malaysia. METHODS: This was a cross
      sectional study using an objectively-scored measure of EI, the Mayer-Salovey
      Caruso Emotional Intelligence Test (MSCEIT). Academic performance of medical
      school students was measured using continuous assessment (CA) and final
      examination (FE) results. The first- and final-year students were invited to
      participate during their second semester. Students answered a paper-based
      demographic questionnaire and completed the online MSCEIT on their own.
      Relationships between the total MSCEIT score to academic performance were
      examined using multivariate analyses. RESULTS: A total of 163 (84 year one and 79
      year five) medical students participated (response rate of 66.0%). The gender and
      ethnic distribution were representative of the student population. The total EI
      score was a predictor of good overall CA (OR 1.01), a negative predictor of poor
      result in overall CA (OR 0.97), a predictor of the good overall FE result (OR
      1.07) and was significantly related to the final-year FE marks (adjusted R(2) =
      0.43). CONCLUSIONS: Medical students who were more emotionally intelligent
      performed better in both the continuous assessments and the final professional
      examination. Therefore, it is possible that emotional skill development may
      enhance medical students' academic performance.

PMID- 23537131
TI  - Stabilization of neutral polyfluorene in aqueous solution through their
      interaction with phospholipids and sol-gel encapsulation.
AB  - Interaction between poly[9,9-bis(6'-bromohexyl)-2,7-fluorene-co-alt-1,4
      phenylene] (PFPBr2), a neutral conjugated polyfluorene which is completely
      insoluble in water, and zwitterionic phospholipids has been investigated in order
      to generate new fluorescent structures which are stable in aqueous media as a
      means of extending the biological applications of these kinds of polymers. Two
      types of differently shaped and composed fluorescent structures were identified
      and then isolated and characterized separately using different biophysical
      techniques. The first structure type, corresponding to liposomal complexes,
      showed a fluorescence band centered around 405 nm and maximum absorption at 345
      nm, while the second, corresponding to polymer-phospholipid aggregates of
      variable sizes with lower lipid content, absorbed at longer wavelengths and
      displayed a well resolved fluorescence spectrum with a maximum centered at 424
      nm. Both structures were stable in a large range of pH, and their fluorescence
      intensity remained practically unaltered for 10 days; it then began to decrease,
      which was probably because of aggregation. Encapsulation of these structures
      within the pores of a sol-gel matrix did not affect their fluorescent properties
      but increased their stability, avoiding further aggregation and subsequent
      precipitation.

PMID- 23537130
TI  - Safety evaluation of the antimicrobial peptide bovicin HC5 orally administered to
      a murine model.
AB  - BACKGROUND: Bovicin HC5 is an antimicrobial peptide that shows a broad spectrum
      of activity and potential for biotechnological and therapeutic applications. To
      gain insight about the safety of bovicin HC5 application, the histological and
      immunostimulatory effects of orally administrated bovicin HC5 to BALB/c mice were
      evaluated. BALB/c mice were divided into three groups: negative control (NC
      group); mice given purified bovicin HC5 (Bov group); mice given ovalbumin
      (positive control, PC group; a murine model of enteropathy). The mice were
      initially pre-sensitized, and PBS, bovicin HC5 or ovalbumin were administered for
      30 days by daily gavages. Histological and morphometric analysis were performed
      and the relative expression of cytokines was analyzed by real-time RT-PCR.
      RESULTS: The oral administration of bovicin HC5 to BALB/c mice reduced weight
      gain and caused alterations in the small intestine, although absorptive changes
      have not been detected. The number of total goblet cells and the
      mucopolysaccharides production were not affected by bovicin HC5 administration. A
      hypertrophy of Paneth cells and an increase in the number of mitotic cells were
      observed in Bov group, while the number of mast cells remained unaltered.
      Increased expression of TNF-alpha, INF-gamma and IL-12 was observed in the small
      intestine upon bovicin HC5 administration. CONCLUSION: Bovicin HC5 has only minor
      effects on intestinal permeability and did not elicit an allergenic response upon
      oral administration to animal models. Considering the low in vivo toxicity of
      bovicin HC5, it might be a good candidate for enteral applications.

PMID- 23537132
TI  - In silico fragment-based drug discovery: setup and validation of a fragment-to
      lead computational protocol using S4MPLE.
AB  - This paper describes the use and validation of S4MPLE in Fragment-Based Drug
      Design (FBDD)--a strategy to build drug-like ligands starting from small
      compounds called fragments. S4MPLE is a conformational sampling tool based on a
      hybrid genetic algorithm that is able to simulate one (conformer enumeration) or
      more molecules (docking). The goal of the current paper is to show that due to
      the judicious design of genetic operators, S4MPLE may be used without any
      specific adaptation as an in silico FBDD tool. Such fragment-to-lead evolution
      involves either growing of one or linking of several fragment-like binder(s). The
      native ability to specifically "dock" a substructure that is covalently anchored
      to its target (here, some prepositioned fragment formally part of the binding
      site) enables it to act like dedicated de novo builders and differentiates it
      from most classical docking tools, which may only cope with non-covalent
      interactions. Besides, S4MPLE may address growing/linking scenarios involving
      protein site flexibility, and it might also suggest "growth" moves by bridging
      the ligand to the site via water-mediated interactions if H2O molecules are
      simply appended to the input files. Therefore, the only development overhead
      required to build a virtual fragment->ligand growing/linking strategy based on
      S4MPLE were two chemoinformatics programs meant to provide a minimalistic
      management of the linker library. The first creates a duplicate-free library by
      fragmenting a compound database, whereas the second builds new compounds,
      attaching chemically compatible linkers to the starting fragments. S4MPLE is
      subsequently used to probe the optimal placement of the linkers within the
      binding site, with initial restraints on atoms from initial fragments, followed
      by an optimization of all kept poses after restraint removal. Ranking is mainly
      based on two criteria: force-field potential energy and RMSD shifts of the
      original fragment moieties. This strategy was applied to several examples from
      the FBDD literature with good results over several monitored criteria: ability to
      generate the optimized ligand (or close analogs), good ranking of analogs among
      decoy compounds, and accurate predictions of expected binding modes of reference
      ligands. Simulations included "classical" covalent growing/linking, more
      challenging ones involving binding site conformational changes, and growth with
      optional recognition of putatively favorable water-mediated interactions.

PMID- 23537133
TI  - Efficient anodic allylation and benzylation of carbons using allyl and benzyl
      trimethylsilanes.
AB  - An easy process for allylation and benzylation of different carbon materials,
      primarily of glassy carbon, in acetonitrile solutions containing
      tetraalkyammonium salts is described. The method relies on the capability of
      C(sp(2)) zones of glassy carbon (graphite and fullerene-like inclusions) to be
      anodically charged at potentials >1.5 V versus Ag/AgCl to form electrophilic
      centers reacting with substituted trimethylsilanes RSiMe3. Great propensity of
      the trimethylsilyl group (TMS(+)) to act as a cationic leaving group facilitates
      electrophilic reactions of the charged anodic surface with R-carrying silylated
      precursors, permitting efficient grafting of a large variety of R groups. The
      present preliminary work focuses only on the efficient grafting of benzyl and
      allyl moieties.

PMID- 23537134
TI  - Challenges in immunodiagnostic tests for leprosy.
AB  - INTRODUCTION: Despite the effectiveness of multidrug therapy, leprosy still
      represents a significant global health problem: transmission of Mycobacterium
      leprae (M. leprae) is not sufficiently reduced as witnessed by unwavering new
      case rates in leprosy-endemic countries. Early detection of M. leprae infection
      (before clinical manifestations occur) is vital to reduction of transmission.
      Current diagnosis relies on detection of clinical signs since there are no tests
      available to detect asymptomatic M. leprae infection or predict progression to
      leprosy. AREAS COVERED: Identification of risk factors (immunological or genetic
      biomarkers) for disease development and/or onset of leprosy reactions is
      imperative for efficient diagnosis. Tests simultaneously detecting biomarkers
      specific for cellular and humoral immunity are well suited for diagnosis of
      different clinical outcomes of leprosy. This review describes the challenges of
      discovery of biomarkers for M. leprae infection and their implementation in field
      friendly tests. EXPERT OPINION: In view of the complicated nature of M. leprae
      infections, it is essential to invest in longitudinal studies allowing intra
      individual comparison of immune and genetic biomarkers in various leprosy-endemic
      areas. Furthermore, the effect of co-infections on biomarker profiles should also
      be taken into account. Diagnostic tests based on such biomarkers can contribute
      significantly to early detection of leprosy (reactions) thus helping reduce nerve
      damage.

PMID- 23537135
TI  - Tidal Venuses: triggering a climate catastrophe via tidal heating.
AB  - Traditionally, stellar radiation has been the only heat source considered capable
      of determining global climate on long timescales. Here, we show that terrestrial
      exoplanets orbiting low-mass stars may be tidally heated at high-enough levels to
      induce a runaway greenhouse for a long-enough duration for all the hydrogen to
      escape. Without hydrogen, the planet no longer has water and cannot support life.
      We call these planets "Tidal Venuses" and the phenomenon a "tidal greenhouse."
      Tidal effects also circularize the orbit, which decreases tidal heating. Hence,
      some planets may form with large eccentricity, with its accompanying large tidal
      heating, and lose their water, but eventually settle into nearly circular orbits
      (i.e., with negligible tidal heating) in the habitable zone (HZ). However, these
      planets are not habitable, as past tidal heating desiccated them, and hence
      should not be ranked highly for detailed follow-up observations aimed at
      detecting biosignatures. We simulated the evolution of hypothetical planetary
      systems in a quasi-continuous parameter distribution and found that we could
      constrain the history of the system by statistical arguments. Planets orbiting
      stars with masses<0.3 MSun may be in danger of desiccation via tidal heating. We
      have applied these concepts to Gl 667C c, a ~4.5 MEarth planet orbiting a 0.3
      MSun star at 0.12 AU. We found that it probably did not lose its water via tidal
      heating, as orbital stability is unlikely for the high eccentricities required
      for the tidal greenhouse. As the inner edge of the HZ is defined by the onset of
      a runaway or moist greenhouse powered by radiation, our results represent a
      fundamental revision to the HZ for noncircular orbits. In the appendices we
      review (a) the moist and runaway greenhouses, (b) hydrogen escape, (c) stellar
      mass-radius and mass-luminosity relations, (d) terrestrial planet mass-radius
      relations, and (e) linear tidal theories.

PMID- 23537136
TI  - Spectral fingerprints of Earth-like planets around FGK stars.
AB  - We present model atmospheres for an Earth-like planet orbiting the entire grid of
      main sequence FGK stars with effective temperatures ranging from Teff=4250 K to
      Teff=7000 K in 250 K intervals. We have modeled the remotely detectable spectra
      of Earth-like planets for clear and cloudy atmospheres at the 1 AU equivalent
      distance from the VIS to IR (0.4 to 20 MUm) to compare detectability of features
      in different wavelength ranges in accordance with the James Webb Space Telescope
      and future design concepts to characterize exo-Earths. We have also explored the
      effect of the stellar UV levels as well as spectral energy distribution on a
      terrestrial atmosphere, concentrating on detectable atmospheric features that
      indicate habitability on Earth, namely, H2O, O3, CH4, N2O, and CH3Cl. The
      increase in UV dominates changes of O3, OH, CH4, N2O, and CH3Cl, whereas the
      increase in stellar temperature dominates changes in H2O. The overall effect as
      stellar effective temperatures and corresponding UV increase is a lower surface
      temperature of the planet due to a bigger part of the stellar flux being
      reflected at short wavelengths, as well as increased photolysis. Earth-like
      atmosphere models show more O3 and OH but less stratospheric CH4, N2O, CH3Cl, and
      tropospheric H2O (but more stratospheric H2O) with increasing effective
      temperature of main sequence stars. The corresponding detectable spectral
      features, on the other hand, show different detectability depending on the
      wavelength observed. We concentrate on directly imaged planets here as a
      framework to interpret future light curves, direct imaging, and secondary eclipse
      measurements of atmospheres of terrestrial planets in the habitable zone at
      varying orbital positions.

PMID- 23537137
TI  - Habitable planets around white and brown dwarfs: the perils of a cooling primary.
AB  - White and brown dwarfs are astrophysical objects that are bright enough to
      support an insolation habitable zone (IHZ). Unlike hydrogen-burning stars, they
      cool and become less luminous with time; hence their IHZ moves in with time. The
      inner edge of the IHZ is defined as the orbital radius at which a planet may
      enter a moist or runaway greenhouse, phenomena that can remove a planet's surface
      water forever. Thus, as the IHZ moves in, planets that enter it may no longer
      have any water and are still uninhabitable. Additionally, the close proximity of
      the IHZ to the primary leads to concern that tidal heating may also be strong
      enough to trigger a runaway greenhouse, even for orbital eccentricities as small
      as 10(-6). Water loss occurs due to photolyzation by UV photons in the planetary
      stratosphere, followed by hydrogen escape. Young white dwarfs emit a large amount
      of these photons, as their surface temperatures are over 10(4) K. The situation
      is less clear for brown dwarfs, as observational data do not constrain their
      early activity and UV emission very well. Nonetheless, both types of planets are
      at risk of never achieving habitable conditions, but planets orbiting white
      dwarfs may be less likely to sustain life than those orbiting brown dwarfs. We
      consider the future habitability of the planet candidates KOI 55.01 and 55.02 in
      these terms and find they are unlikely to become habitable.

PMID- 23537138
TI  - Research focus group activity of the Sao Paulo Advanced School of Astrobiology:
      SPASA 2011.

PMID- 23537140
TI  - Parallel beta-sheet fibril and antiparallel beta-sheet oligomer: new insights
      into amyloid formation of hen egg white lysozyme under heat and acidic condition
      from FTIR spectroscopy.
AB  - Hen egg white lysozyme (HEWL) is widely used as a model protein for amyloid
      research. In this study, we aim to use Fourier transform infrared (FTIR)
      spectroscopy to gain new structural insights into amyloid formation of HEWL under
      heat and acidic condition. We reveal that the fibril-forming solution of HEWL has
      the capability to form fibril and oligomer with distinct beta-sheet
      configurations under different temperatures. Amyloid fibril with parallel beta
      sheet configuration is formed at elevated temperature, while oligomer with
      antiparallel beta-sheet configuration is formed at room temperature. The
      interplay between fibrillation and oligomerization suggests that the two beta
      sheet aggregates consume the same amyloidogenic materials such as peptide
      fragments and nicked HEWL due to lysozyme hydrolysis under heat and acidic
      condition. Temperature-dependent FTIR reveals that the oligomer is unstable at
      elevated temperature, demonstrating its off-pathway nature. The temperature
      dependent formation of parallel and antiparallel beta-sheet configurations
      discovered in lysozyme system is compared with that of amyloid-beta and alpha
      synuclein systems and the implication is discussed.

PMID- 23537139
TI  - Low concordance of multiple variant-calling pipelines: practical implications for
      exome and genome sequencing.
AB  - BACKGROUND: To facilitate the clinical implementation of genomic medicine by next
      generation sequencing, it will be critically important to obtain accurate and
      consistent variant calls on personal genomes. Multiple software tools for variant
      calling are available, but it is unclear how comparable these tools are or what
      their relative merits in real-world scenarios might be. METHODS: We sequenced 15
      exomes from four families using commercial kits (Illumina HiSeq 2000 platform and
      Agilent SureSelect version 2 capture kit), with approximately 120X mean coverage.
      We analyzed the raw data using near-default parameters with five different
      alignment and variant-calling pipelines (SOAP, BWA-GATK, BWA-SNVer, GNUMAP, and
      BWA-SAMtools). We additionally sequenced a single whole genome using the
      sequencing and analysis pipeline from Complete Genomics (CG), with 95% of the
      exome region being covered by 20 or more reads per base. Finally, we validated
      919 single-nucleotide variations (SNVs) and 841 insertions and deletions
      (indels), including similar fractions of GATK-only, SOAP-only, and shared calls,
      on the MiSeq platform by amplicon sequencing with approximately 5000X mean
      coverage. RESULTS: SNV concordance between five Illumina pipelines across all 15
      exomes was 57.4%, while 0.5 to 5.1% of variants were called as unique to each
      pipeline. Indel concordance was only 26.8% between three indel-calling pipelines,
      even after left-normalizing and intervalizing genomic coordinates by 20 base
      pairs. There were 11% of CG variants falling within targeted regions in exome
      sequencing that were not called by any of the Illumina-based exome analysis
      pipelines. Based on targeted amplicon sequencing on the MiSeq platform, 97.1%,
      60.2%, and 99.1% of the GATK-only, SOAP-only and shared SNVs could be validated,
      but only 54.0%, 44.6%, and 78.1% of the GATK-only, SOAP-only and shared indels
      could be validated. Additionally, our analysis of two families (one with four
      individuals and the other with seven), demonstrated additional accuracy gained in
      variant discovery by having access to genetic data from a multi-generational
      family. CONCLUSIONS: Our results suggest that more caution should be exercised in
      genomic medicine settings when analyzing individual genomes, including
      interpreting positive and negative findings with scrutiny, especially for indels.
      We advocate for renewed collection and sequencing of multi-generational families
      to increase the overall accuracy of whole genomes.

PMID- 23537141
TI  - Heparanase patents: dim past and bright future.
AB  - Heparanase is an enzyme expressed normally in platelets and in placenta at high
      levels, and is undetectable in other normal human tissues. Heparanase degrades
      the heparan sulfate saccharides of the extracellular matrix. The real problem
      starts when tumor cells express heparanase; this results in increased tumor
      angiogenesis, aggressiveness, and metastasis. Patents filed on heparanase
      detection, suppression, and function modulation were not translated yet into
      products (tested in Phase III trials). The mismatch between researchers,
      clinicians, and pharmaceutical companies, which identified the first 20 years of
      heparanase research, is changing and will hopefully foster the arrival of some of
      these patent inventions for clinical applicability.

PMID- 23537142
TI  - The influence of commercially-available carbohydrate and carbohydrate-protein
      supplements on endurance running performance in recreational athletes during a
      field trial.
AB  - BACKGROUND: It is recommended that endurance athletes consume carbohydrate (CHO)
      supplements, providing 6-8% CHO concentration, during exercise > 60 minutes to
      improve athletic performance. Recently research has compared carbohydrate-protein
      (CHO-P) supplementation to the traditionally used CHO supplementation during
      endurance exercise, following these supplementation recommendations, in
      controlled settings, but not under simulated applied conditions such as a field
      trial. Therefore, the purpose of the present investigation was to test CHO and
      CHO-P supplementation under applied conditions such that commercially-available
      isocaloric (CHO-P & double-carbohydrate [CHO-CHO]) and isocarbohydrate (CHO-P &
      CHO) supplements were compared to a placebo (PLA), within an outdoor running
      field trial > 60 minutes in order to asses their influence on endurance
      performance. METHODS: Twelve male recreational runners completed four, 19.2 km
      runs, where they were instructed to run at a pace similar to race pace including
      a final sprint to the finish, which in this case was the final two laps of the
      course (1.92 km). Supplementation was provided before the start and in 4 km
      increments. Performance was measured by time to complete the 19.2 km run and last
      1.92 km sprint. RESULTS: Analyses found no difference between supplements in time
      to complete the 19.2 km run (PLA = 88.6 +/- 11.6 min, CHO = 89.1 +/- 11.3 min,
      CHO-P = 89.1 +/- 11.8 min, CHO-CHO = 89.6 +/- 11.9 min) or last 1.92 km sprint to
      the finish (PLA = 8.3 +/- 1.2 min, CHO = 8.2 +/- 1.2 min, CHO-P = 8.2 +/- 1.2
      min, CHO-CHO = 8.4 +/- 1.5 min). CONCLUSIONS: When following recommendation for
      supplementation within a field trial, commercially available CHO and CHO-P
      supplements do not appear to enhance performance in male recreational runners.

PMID- 23537143
TI  - The reliability and validity of the Questionnaire - Children with Difficulties
      (QCD).
AB  - BACKGROUND: The aim of this study was to evaluate the reliability and validity of
      the Questionnaire-Children with Difficulties (QCD), which was developed for the
      evaluation of children's daily life behaviors during specified periods of the
      day. METHODS: The subjects were 1,514 Japanese public elementary and junior high
      school students. For the examination of reliability, Cronbach's alpha was
      calculated to assess the internal consistency of the questionnaire. With regard
      to validity, correlation coefficients were calculated to examine whether QCD
      scores correlated with those of the ADHD-Rating Scale (ADHD-RS) and the
      Oppositional Defiant Behavior Inventory (ODBI). RESULTS: Cronbach's alpha
      coefficient for the total score of the QCD was .876. The correlation coefficients
      of the QCD score with ADHD-RS and ODBI scores were -.514 and -.577, respectively.
      CONCLUSIONS: The internal consistency and validity of the QCD were demonstrated.
      The QCD is a reliable and valid instrument for evaluating daily life problems for
      children during different time periods of the day.

PMID- 23537144
TI  - Models of professional regulation: institutionalizing an agency relationship.
AB  - The regulation of medical practice can historically be understood as a second
      level agency relationship whereby the state delegated authority to professional
      bodies to police the primary agency relationship between the individual physician
      and the patient. Borow, Levi and Glekin show how different national systems vary
      in the degree to which they insist on institutionally insulating the agency
      function from the promotion of private professional interests, and relate these
      variations to different models of the health care state. In fact these
      differences have even deeper roots in different "liberal" or "coordinated"
      varieties of capitalist political economies. Neither model is inherently more
      efficient than the other: what matters is the internal coherence or logic of
      these systems that conditions the expectations of actors in responding to
      particular challenges. The territory that Borow, Levi and Glekin have usefully
      mapped invites further exploration in this regard.This is a commentary on
      http://www.ijhpr.org/content/2/1/8.

PMID- 23537145
TI  - Misclassification of Plasmodium infections by conventional microscopy and the
      impact of remedial training on the proficiency of laboratory technicians in
      species identification.
AB  - BACKGROUND: Malaria diagnosis is largely dependent on the demonstration of
      parasites in stained blood films by conventional microscopy. Accurate
      identification of the infecting Plasmodium species relies on detailed examination
      of parasite morphological characteristics, such as size, shape, pigment granules,
      besides the size and shape of the parasitized red blood cells and presence of
      cell inclusions. This work explores misclassifications of four Plasmodium species
      by conventional microscopy relative to the proficiency of microscopists and
      morphological characteristics of the parasites on Giemsa-stained blood films.
      CASE DESCRIPTION: Ten-day malaria microscopy remedial courses on parasite
      detection, species identification and parasite counting were conducted for public
      health and research laboratory personnel. Proficiency in species identification
      was assessed at the start (pre) and the end (post) of each course using known
      blood films of Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale and
      Plasmodium vivax infections with densities ranging from 1,000 to 30,000
      parasites/MUL. Outcomes were categorized as false negative, positive without
      speciation, P. falciparum, P. malariae, P. ovale, P. vivax and mixed infections.
      DISCUSSION AND EVALUATION: Reported findings are based on 1,878 P. falciparum,
      483 P. malariae, 581 P. ovale and 438 P. vivax cumulative results collated from
      2008 to 2010 remedial courses. Pre-training false negative and positive
      misclassifications without speciation were significantly lower on P. falciparum
      infections compared to non-falciparum infections (p < 0.0001). Post-training
      misclassifications decreased significantly compared to pre- training
      misclassifications which in turn led to significant improvements in the
      identification of the four species. However, P. falciparum infections were highly
      misclassified as mixed infections, P. ovale misclassified as P. vivax and P.
      vivax similarly misclassified as P. ovale (p < 0.05). CONCLUSION: These findings
      suggest that the misclassification of malaria species could be a common
      occurrence especially where non-falciparum infections are involved due to lack of
      requisite skills in microscopic diagnosis and variations in morphological
      characteristics within and between Plasmodium species. Remedial training might
      improve reliability of conventional light microscopy with respect to
      differentiation of Plasmodium infections.

PMID- 23537146
TI  - Genetic analysis of peste des petits ruminants virus from Pakistan.
AB  - BACKGROUND: Peste des petits ruminants (PPR) is an endemic and highly contagious
      disease in small ruminants of Pakistan. Despite the fact that an effective
      vaccine is available, outbreaks are regularly occurring in the country. Thus so
      far, the diagnosis has primarily been made based on clinical outcome or serology.
      This study was carried out to characterize PPRV from an emerging wave of
      outbreaks from Punjab, Pakistan. RESULTS: A total of 32 blood samples from five
      different flocks were tested with real-time PCR for the presence of PPRV genome.
      The samples detected positive in real-time PCR (n = 17) were subjected to
      conventional PCR for the amplification of the nucleoprotein (N) gene.
      Phylogenetic analysis of the sequenced N genes (n = 8) indicated the grouping of
      all the sequences in lineage IV along with PPRV strains from Asian and Middle
      East. However, interestingly sequences were divided into two groups. One group of
      viruses (n = 7) clustered with previously characterized Pakistani isolates
      whereas one strain of PPRV was distinct and clustered with Saudi Arabian and
      Iranian strains of PPRV. CONCLUSIONS: Results demonstrated in this study expanded
      the information on the genetic nature of different PPRV population circulating in
      small ruminants. Such information is essential to understand genetic nature of
      PPRV strains throughout the country. Proper understanding of these viruses will
      help to devise control strategies in PPRV endemic countries such as Pakistan.

PMID- 23537147
TI  - Increasing Hepatitis C treatment uptake among HIV-infected patients using an HIV
      primary care model.
AB  - BACKGROUND: Access to Hepatitis C (HCV) care is low among HIV-infected
      individuals, highlighting the need for new models to deliver care for this
      population. METHODS: Retrospective cohort analysis that compared the number of
      HIV patients who initiated HCV therapy: hepatology (2005-2008) vs. HIV primary
      care model (2008-2011). Logistic-regression modeling was used to ascertain
      factors associated with HCV therapy initiation and achievement of sustained viral
      response (SVR). RESULTS: Of 196 and 163 patients that were enrolled in the HIV
      primary care and hepatology models, 48 and 26 were treated for HCV, respectively
      (p = 0.043). The HIV/HCV-patient referral rate did not differ during the two
      study periods (0.10 vs. 0.12/patient-yr, p = 0.18). In unadjusted analysis,
      predictors (p < 0.05) of HCV treatment initiation included referral to the HIV
      primary care model (OR: 1.7), a CD4+ count >=400/mm3 (OR: 1.8) and alanine
      aminotranferase level >=63U/L (OR: 1.9). Prior psychiatric medication use
      correlated negatively with HCV treatment initiation (OR: 0.6, p = 0.045). In
      adjusted analysis the strongest predictor of HCV treatment initiation was CD4+
      count (>=400/mm3, OR: 2.1, p = 0.01). There was no significant difference in
      either clinic model (primary care vs. hepatology) in the rates of treatment
      discontinuation due to adverse events (29% vs. 16%), loss to follow-up (8 vs.
      8%), or HCV SVR (44 vs. 35%). CONCLUSIONS: Using a HIV primary care model
      increased the number of HIV patients who initiate HCV therapy with comparable
      outcomes to a hepatology model.

PMID- 23537148
TI  - Effects of diquafosol tetrasodium administration on visual function in short
      break-up time dry eye.
AB  - PURPOSE: To investigate the effect of diquafosol tetrasodium on tear and visual
      function in short break-up time (sBUT) dry eye (DE). METHODS: This interventional
      nonrandomized comparative study involved 11 eyes in 11 patients with sBUT DE
      (symptom-positive sBUT group) and 13 eyes in 13 volunteers with BUT values <=5 s
      without DE symptoms (symptom-negative sBUT group). Tear function was assessed by
      measuring BUT and Schirmer values. Serial measurements were made of visual
      acuities (using a functional visual acuity measurement system) and higher-order
      aberrations (using a wavefront sensor). The parameters were compared before and 1
      month after diquafosol tetrasodium instillation. Any changes in symptomatology
      after administration were also recorded. RESULTS: After diquafosol tetrasodium
      administration, BUT values tended to increase in the symptom-positive sBUT group
      (P=0.07) and significantly increased in the symptom-negative sBUT group (P<0.05).
      LogMAR functional, minimal, and maximal visual acuities and higher-order
      aberrations significantly decreased after diquafosol tetrasodium administration
      in the symptom-positive sBUT group (P<0.05), while there were no significant
      changes in these values in the symptom-negative sBUT group (P>0.05). Diquafosol
      tetrasodium administration provided relief of DE symptoms in 75% of patients in
      the symptom-positive sBUT group. CONCLUSIONS: Diquafosol tetrasodium appeared to
      improve tear film stability and visual function in sBUT DE.

PMID- 23537149
TI  - Baicalein protects against retinal ischemia by antioxidation, antiapoptosis,
      downregulation of HIF-1alpha, VEGF, and MMP-9 and upregulation of HO-1.
AB  - PURPOSE: Retinal ischemia-associated ocular disorders are vision threatening.
      This study examined whether the flavonoid baicalein is able to protect against
      retinal ischemia/reperfusion. METHODS: Using rats, the intraocular pressure was
      raised to 120 mmHg for 60 min to induce retinal ischemia. In vitro, an ischemic
      like insult, namely oxidative stress, was established by incubating dissociated
      retinal cells with 100 MUM ascorbate and 5 MUM FeSO4 (iron) for 1 h. The rats or
      the dissociated cells had been pretreated with baicalein (in vivo: 0.05 or 0.5
      nmol; in vitro: 100 MUM), vehicle (1% ethanol), or trolox (in vivo: 5 nmol; in
      vitro: 100 MUM or 1 mM). The effects of these treatments on the retina or the
      retinal cells were evaluated by electrophysiology, immunohistochemistry, terminal
      deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining,
      Western blotting, or in vitro dichlorofluorescein assay. In addition, real-time
      polymerase chain reaction was used to assess the retinal expression of hypoxia
      inducible factor-1alpha (HIF-1alpha), matrix metalloproteinase-9 (MMP-9),
      vascular endothelium growth factor (VEGF), and heme oxygenase-1 (HO-1). RESULTS:
      The retinal changes after ischemia included a decrease in the electroretinogram b
      wave amplitude, a loss of choline acetyltransferase immunolabeling amacrine cell
      bodies/neuronal processes, an increase in vimentin immunoreactivity, which is a
      marker for Muller cells, an increase in apoptotic cells in the retinal ganglion
      cell layer linked to a decrease in the Bcl-2 protein, and changes in the mRNA
      levels of HIF-1alpha, VEGF, MMP-9, and HO-1. Of clinical importance, the ischemic
      detrimental effects were concentration dependently and/or significantly (0.05
      nmol and/or 0.5 nmol) altered when baicalein was applied 15 min before retinal
      ischemia. Most of all, 0.5 nmol baicalein significantly reduced the upregulation
      of MMP-9; in contrast, 5 nmol trolox only had a weak attenuating effect. In
      dissociated retinal cells subjected to ascorbate/iron, there was an increase in
      the levels of reactive oxygen species, which had been significantly attenuated by
      100 MUM baicalein and trolox (100 MUM or 1 mM; a stronger antioxidative effect at
      1 mM). CONCLUSIONS: Baicalein would seem to protect against retinal ischemia via
      antioxidation, antiapoptosis, upregulation of HO-1, and downregulation of HIF
      1alpha, VEGF, and MMP-9. The antioxidative effect of baicalein would appear to
      play a minor role in downregulation of MMP-9.

PMID- 23537150
TI  - Meta-analysis of the effect of intravitreal bevacizumab in branch retinal vein
      occlusion.
AB  - BACKGROUND: To further evaluate the effect of intravitreal bevacizumab (IVB) for
      the treatment of branch retinal vein occlusion in a meta-analysis of previous
      studies. METHODS: Pertinent publications were identified through systemic
      searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register up to
      July 2012. Data on central macular thickness and best-corrected visual acuity
      obtained at 4 and 12 weeks after treatment were extracted. Groups of patients
      receiving IVB were compared with control groups. RESULTS: Four randomized
      controlled and 3 comparative studies were included. A publication bias was not
      detected by funnel plots, the Egger method, or the Begg method. Best corrected
      visual acuity measured at 4 and 12 weeks after baseline increased significantly
      in the IVB groups as compared with the control groups [4 weeks: weighted mean
      deviation (WMD)=-0.09; 95% confidence interval (CI): -0.12, -0.05; P<0.001; at 12
      weeks: WMD=-0.21; 95% CI: -0.30, -0.12; P<0.001]. Similarly, reduction in central
      macular thickness at 12 weeks after baseline was significantly higher in the IVB
      groups than in the control groups (WMD=-29.02; 95% CI: -50.56, -7.49; P=0.008).
      The change in central macular thickness at 4 weeks after baseline did not vary
      significantly between the IVB groups and control groups (WMD=-20.48; 95% CI: 
      67.30, 26.34; P=0.39). All included studies taken separately reported on a
      significant increase in visual acuity in the IVB groups. CONCLUSIONS: Patients
      with branch retinal vein occlusion experienced a significant benefit in terms of
      visual improvement and reduction in central macular thickness after the
      intravitreal injection of bevacizumab.

PMID- 23537151
TI  - Can Brazil play a more important role in global tuberculosis drug production? An
      assessment of current capacity and challenges.
AB  - BACKGROUND: Despite the existence of effective treatment, tuberculosis is still a
      global public health issue. The World Health Organization recommends a six-month
      four-drug regimen in fixed-dose combination formulation to treat drug sensitive
      tuberculosis, and long course regimens with several second-line drugs to treat
      multi-drug resistant tuberculosis. To achieve the projected tuberculosis
      elimination goal by 2050, it will be essential to ensure a non-interrupted supply
      of quality-assured tuberculosis drugs. However, quality and affordable
      tuberculosis drug supply is still a significant challenge for National
      Tuberculosis Programs. DISCUSSION: Quality drug production requires a combination
      of complex steps. The first challenge is to guarantee the quality of tuberculosis
      active pharmaceutical ingredients, then ensure an adequate manufacturing process,
      according to international standards, to guarantee final product's safety,
      efficacy and quality. Good practices for storage, transport, distribution and
      quality control procedures must follow. In contrast to other high-burden
      countries, Brazil produces tuberculosis drugs through a strong network of public
      sector drug manufacturers regulated by a World Health Organization-certified
      national sanitary authority. The installed capacity for production surpasses the
      71,000 needed treatments in the country. However, in order to be prepared to act
      as a global supplier, important bottlenecks are to be overcome. This article
      presents an in-depth analysis of the current status of production of tuberculosis
      drugs in Brazil and the bottlenecks and opportunities for the country to sustain
      national demand and play a role as a potential global supplier. Raw material and
      drug production, quality control, international certification and pre
      qualification, political commitment and regulatory aspects are discussed, as well
      recommendations for tackling these bottlenecks. This discussion becomes more
      important as new drugs and regimens to treat tuberculosis are expected in a close
      future. SUMMARY: International manufacturers of raw material for tuberculosis
      treatment should undergo certification and pre-qualify their active
      pharmaceutical ingredients as a first step to ensure quality of tuberculosis
      drugs. At the country level, Brazilian public manufacturers should apply for
      international certification and tuberculosis drugs should be pre-qualified by
      international organisms. Finally, only with political commitment and large-scale
      production will Brazilian public sector manufacturers be able to partially supply
      the global market.

PMID- 23537153
TI  - Implementation of a clinical pharmacy specialist-managed telephonic hospital
      discharge follow-up program in a patient-centered medical home.
AB  - The objectives of this retrospective study were to examine the feasibility and
      characteristics that define successful implementation of a Clinical Pharmacy
      Specialist (CPS) telephonic hospital discharge follow-up quality improvement
      initiative, as well as the impact of this initiative. Adult patients who were
      discharged from a safety-net hospital between July 1, 2010 and June 30, 2011 and
      who were part of a patient-centered medical home were included in this quality
      improvement initiative. CPSs attempted to contact 470 patients; of those, 207
      received the intervention and 263 did not. Patients in the contacted group were
      more likely to attend a hospital discharge follow-up appointment (66.2% vs.
      44.5%, P<0.01) and had lower rates of 30-day readmission (22 vs. 52, P<0.01)
      compared to those who were not contacted. Institutions should consider allocating
      resources for pharmacist-managed posthospital discharge follow-up services
      because of the potential for positive clinical and financial impact.

PMID- 23537152
TI  - Very advanced maternal age and morbidity in Victoria, Australia: a population
      based study.
AB  - BACKGROUND: In Australia, approximately 0.1% of births occur to women 45 years or
      older and this rate has been increasing in recent years. There are however, few
      population based studies examining perinatal outcomes among this age group. The
      aim of this study was to determine the maternal and perinatal outcomes of
      pregnancies in women aged 45 years or older compared to women aged 30-34 years.
      METHODS: Data on births at 20 or more weeks' gestation were obtained from the
      Victorian Perinatal Data Collection for the years 2005 and 2006. We examined
      selected maternal and perinatal outcomes for women of very advanced maternal age
      (VAMA) aged 45 years or older (n = 217) and compared them to women aged 30-34
      years (n = 48,909). Data were summarised using numbers and percentages.
      Categorical data were analysed by Chi-square tests and Fisher's exact test.
      Comparisons are presented using unadjusted odds ratios, 95 percent confidence
      intervals (CIs) and p-values. RESULTS: Women aged 45 years and older had higher
      odds of gestational diabetes (OR 2.05; 95% CI 1.3-3.3); antepartum haemorrhage
      (OR 1.89; 95% CI 1.01-3.5), and placenta praevia (OR 4.88; 95% CI 2.4-9.5). The
      older age-group also had higher odds of preterm birth between 32-36 weeks (OR
      2.61; 95% CI 1.8-3.8); low birth-weight (<2,500 gr) (OR 2.22; 95% CI 1.5-3.3) and
      small for gestational age (OR 1.53; 95% CI 1.0-2.3). Stratified analysis revealed
      that VAMA was most strongly associated with caesarean section in primiparous
      women (OR 8.24; 95% CI 4.5, 15.4) and those using ART (OR 5.75; 95% CI 2.5,
      13.3), but the relationship persisted regardless of parity, ART use and
      plurality. Low birthweight was associated with VAMA only in first births (OR
      3.90; 95% CI 2.3, 6.6), while preterm birth was more common in older women for
      both first (OR 3.13; 95% CI 1.8, 5.3) and subsequent (OR 2.08; 95% CI 1.2, 3.5)
      births, and for those having singleton births (OR 2.11; 95% CI 1.3, 3.4), and
      those who did not use ART (OR 2.10; 95% CI 1.3, 3.4). Preterm birth was very
      common in multiple births and following ART use, regardless of maternal age.
      CONCLUSIONS: This study demonstrates that women aged 45 years and older, in
      Victoria, Australia, have higher rates of pregnancy and perinatal complications,
      compared to women aged 30-34 years.

PMID- 23537155
TI  - Coalitions for impacting the health of a community: the Summit County, Ohio,
      experience.
AB  - Community coalitions have the potential to catalyze important changes in the
      health and well-being of populations. The authors demonstrate how communities can
      benefit from a multisector coalition to conduct a community-wide surveillance,
      coordinate activities, and monitor health and wellness interventions. Data from
      Summit County, Ohio are presented that illustrate how this approach can be framed
      and used to impact community health positively across communities nationwide. By
      jointly sharing the responsibility and accountability for population health
      through coalitions, communities can use the Health Impact Pyramid framework to
      assess local assets and challenges and to identify and implement programmatic and
      structural needs. Such a coalition is well poised to limit duplication and to
      increase the efficiency of existing efforts and, ultimately, to positively impact
      the health of a population.

PMID- 23537154
TI  - The influence of a postdischarge intervention on reducing hospital readmissions
      in a Medicare population.
AB  - Hospital readmissions in the Medicare population may be related to a number of
      factors, including reoccurrence of illness, failure to understand or follow
      physician direction, or lack of follow-up care, among others. These readmissions
      significantly increase cost and utilization in this population, and are expected
      to increase with the projected growth in Medicare enrollment. The authors
      examined whether a postdischarge telephonic intervention for patients reduced 30
      day hospital readmissions as compared to a matched control population.
      Postdischarge telephone calls were placed to patients after discharge from a
      hospital. Readmissions were monitored through health care claims data analysis.
      Of 48,538 Medicare members who received the intervention, 4504 (9.3%) were
      readmitted to the hospital within 30 days, as compared to 5598 controls (11.5%,
      P<0.0001). A direct correlation was observed between the timing of the
      intervention and the rate of readmission; the closer the intervention to the date
      of discharge the greater the reduction in number of readmissions. Furthermore,
      although emergency room visits were reduced in the intervention group as compared
      to controls (8.1% vs. 9.4%, P<0.0001), physician office visits increased (76.5%
      vs. 72.3%, P<0.0001), suggesting the intervention may have encouraged members to
      seek assistance leading to avoidance of readmission. As a group, overall cost
      savings were $499,458 for members who received the intervention, with $13,964,773
      in savings to the health care plan. Support for patients after hospital discharge
      clearly affected hospital readmission and associated costs and warrants further
      development.

PMID- 23537156
TI  - Disseminating evidence-based care into practice.
AB  - The Centers for Medicare and Medicaid Services (CMS) has launched the Partnership
      for Patients initiative, promising a 20% reduction in readmissions nationally
      across all payers by December 31, 2013. To address this ambitious goal, CMS has
      awarded grants to Hospital Engagement Networks, Pioneer Accountable Care
      Organizations, and the Community-based Care Transitions Program, as well as
      instituted new penalties for excessive readmission that began in October 2012.
      National efforts aimed at realizing this goal are predicated, in part, on our
      effectiveness in disseminating evidence-based care models into practice to
      improve outcomes and reduce costs. The Care Transitions Intervention (CTI) has
      been developed, tested, and disseminated to over 750 health care organizations in
      40 states nationwide. Four factors promote wide-scale CTI dissemination. The
      first factor focuses on model fidelity whereby adopters are given insight into
      which elements of the intervention can be adapted and customized. The second
      factor concerns the selection of Transitions Coaches and reinforcement of their
      role through training and participation in a national peer learning network. The
      third factor relates to model execution with attention to integrating the
      intervention into existing workflows and fostering relationships with community
      stakeholders. The fourth factor involves cultivating the support to sustain or
      expand the intervention through continually making the business case in a
      changing health care landscape. The lessons learned through the dissemination and
      implementation of the CTI may be generalizable to the spread of a variety of
      evidence-based care models.

PMID- 23537157
TI  - The influence of age on the management of patients with diabetes in the Israeli
      population.
AB  - The authors' aim was to study the association between age and the quality of
      community health care of diabetes mellitus (DM). This was a cross-sectional study
      of patients with DM in the setting of a large health maintenance organization
      (HMO) in Israel. The population included DM patients aged 40-84 years who were
      identified at emergency rooms or through the HMO's computerized database. A set
      of quality care indicators were determined. Logistic regressions were used to
      estimate the odds ratios (OR) for diabetes care indicators, controlling for age
      and other potential confounders. Older patients were more likely to be in the
      target range of glycemic control and to be vaccinated against influenza. Patients
      older than age 70 years received fewer recommendations for physical activity (OR
      0.41, P<0.01) and self-foot examination (OR 0.57, P=0.024). The authors found
      decreased performance of recommendations for physical activity and self-foot
      examination, and a higher performance of annual blood tests and immunizations
      among elderly patients with diabetes.

PMID- 23537158
TI  - Self-rated stress is noncontributory to coronary artery disease in higher
      socioeconomic strata.
AB  - Stress and its attendant psychosocial and lifestyle variables have been
      associated with coronary artery disease (CAD), yet the contribution of
      socioeconomic status (SES) has not been addressed. The aim of this study is to
      determine if stress assessment is associated with CAD independent of SES, and is
      incremental to the Framingham Score. The study group consisted of 325 executive
      patients undergoing comprehensive health assessment. Stress was assessed
      utilizing the validated "Self-Rated Stress" (SRS) instrument. Coronary artery
      calcification (CAC) served to assess the degree of atherosclerosis, a CAD
      equivalent and risk assessment tool. The relationship between SRS and CAC was
      assessed, with adjustment by potential confounders. CAC was modeled by a variety
      of cut points (>0, >=5, >=100, >=200) for the test of trend across stress levels
      per Mantel-Haenszel chi-square (1 df) with nonsignificant P values of 0.9960,
      0.5242, 0.1692, 0.3233, respectively. A logistic regression model with SRS as a
      categorically ranked and continuous variable to predict binary outcome of
      calcification yielded P values of 0.2366 and 0.9644; this relationship, further
      adjusted by age, fruit and vegetable consumption, exercise, and education,
      yielded no statistically significant association. No improvement of fit was
      observed for the established Framingham Score to CAC relation utilizing SRS. The
      study concluded that SRS did not play a role in early CAD when focusing on a
      population in higher socioeconomic strata, and SRS did not add predictive value
      beyond patient age or calculated Framingham risk. Future studies should focus on
      additional validated instruments of stress to differentiate between subtypes of
      stress for varying SES strata.

PMID- 23537159
TI  - Nurse practitioners and physician assistants are complements to family medicine
      physicians.
AB  - Controlling the overall cost of medical care requires controlling the number of
      physician visits. Nurse practitioners and physician assistants (NPs/PAs) may
      function as lower-cost substitutes for physicians or they may complement
      physician services. The association between NP/PA and physician visits when
      NPs/PAs are not working as primary care providers (PCPs) has not been thoroughly
      studied. A sample of 400 family medicine patients drawn from 1 large multisite
      practice was studied using multiple logistic regression analysis. NPs/PAs did not
      function as PCPs during the study period. Patients were defined as outliers if
      they visited physicians more than 5 times in a year. Patients who visited NPs/PAs
      in non-retail clinics were significantly more likely to be physician visit
      outliers. Visits to NPs/PAs in retail clinics were not related to physician
      visits. NP/PA visits in standard medical office settings complement physician
      visits when the NPs/PAs were not working as PCPs in this large multisite
      practice. Health care reform proposals relying on increased use of NPs/PAs may be
      more cost-efficient if NPs/PAs are located in retail settings or function as
      PCPs.

PMID- 23537160
TI  - New triterpene glycoside and other chemical constituents from the leaves of
      Swartzia apetala Raddi var. glabra.
AB  - A new triterpene saponin (1) was isolated from a methanol extract of Swartzia
      apetala Raddi var. glabra, together with the flavonoids mauritianin (2),
      kaempferol (3) and the triterpene saponin beta-D-glucopyranosyl 3beta-hydroxy
      olean-12-en-28-oate (4). These compounds were characterised on the basis of their
      spectral data, mainly one-dimension (1D; (1)H, (13)C, APT) and two-dimension (2D;
      (1)H-(1)H-COSY, HMQC and HMBC) nuclear magnetic resonance (NMR) and HR-ESI-MS,
      and comparison with values in the literature. The analysis by HR-ESI-MS showed a
      mass compatible with that of triterpene saponin 1. This proposal was supported by
      molecular modelling. LC-HR-ESI-MS experiment was also used to evaluate the purity
      of 1 and allowed to speculate about the possibility of the presence of 5 in very
      small quantity. The extract and four compounds were assayed for antifungal
      activity against nine strains of Candida spp. 

PMID- 23537161
TI  - Combined cell culture-biosensing platform using vertically aligned patterned
      peptide nanofibers for cellular studies.
AB  - This Article presents the development of a combined cell culture-biosensing
      platform using vertically aligned self-assembled peptide nanofibers. Peptide
      nanofibers were patterned on a microchip containing gold microelectrodes to
      provide the cells with a 3D environment enabling them to grow and proliferate.
      Gold microelectrodes were functionalized with conductive polymers for the
      electrochemical detection of dopamine released from PC12 cells. The combined cell
      culture-biosensing platform assured a close proximity of the release site, the
      cells and the active surface of the sensor, thereby rendering it possible to
      avoid a loss of sensitivity because of the diffusion of the sample. The obtained
      results showed that the peptide nanofibers were suitable as a cell culturing
      substrate for PC12 cells. The peptide nanofibers could be employed as an
      alternative biological material to increase the adherence properties of PC12
      cells. Dopamine was amperometrically detected at a value of 168 fmole.

PMID- 23537162
TI  - What are effects of a spaced activation of virtual patients in a pediatric
      course?
AB  - BACKGROUND: Virtual patients (VPs) have a long tradition in the curriculum of the
      medical faculty at the Ludwig-Maximilians-University (LMU) Munich. However, the
      pediatric VPs were not well integrated into the curriculum and hardly used by
      students. METHODS: Therefore we created and implemented a self-contained E
      learning module based on virtual patients (VPs), which was embedded into the
      pediatric curriculum.Students taking this course were divided into two groups.
      For Group A the virtual patients were activated in a timed order ("spaced
      activation"), whereas Group B could work on all VPs from the beginning.We
      investigated the performance of these two groups concerning usage pattern
      including number of sessions and session duration, score on questions integrated
      into the VP and results of the intermediate exam. RESULTS: The integration of the
      VPs into the pediatric course was successful for both groups. The usage pattern
      for the spaced activation turned out to be more balanced, however we did not find
      any significant differences in the results of the intermediate exam, the score on
      questions included in the VPs nor in the time students spent working on the VPs.
      CONCLUSIONS: Our study showed that the spaced activation led to a more balanced
      VP usage pattern with a lower peak of sessions at the end of the course. Further
      studies will have to investigate whether a spaced activation of VPs leads to
      favorable long-term learning outcomes.

PMID- 23537163
TI  - Frequency of multi-dimensional COPD indices and relation with disease activity
      markers.
AB  - Our aim was to describe the population-based distribution of several COPD multi
      dimensional indices and to evaluate their relationship with daily physical
      activity, co-morbidity, health status and systemic inflammatory biomarkers. From
      a population-based sample of 3,802 subjects aged 40-80 from the EPI-SCAN study,
      382 subjects (10.2%) with a post-bronchodilator FEV1/FVC<0.7 were identified as
      COPD. Smoking habits, respiratory symptoms, quality of life, co-morbidities, lung
      function and inflammatory biomarkers were recorded. Health status and daily
      physical activity were assessed using the EQ-5D and LCADL questionnaires,
      respectively. The new GOLD grading and the BODE, ADO, DOSE, modified DOSE, e
      BODE, BODEx, CPI, SAFE and HRS indices were determined. A notable dispersion in
      the total scores was observed, although 83-88% of the COPD patients were
      classified into the mildest level and 1-3% in the most severe. The SAFE index was
      the best independent determinant of daily physical activity; the SAFE and ADO
      indices were associated with presence of co-morbidity; and the SAFE and modified
      DOSE indices were independently related to health status. The systemic biomarkers
      showed a less consistent relation with several indices. In a population-based
      sample of COPD patients, the SAFE index reaches the highest relation with
      physical activity, co-morbidity and health status.

PMID- 23537164
TI  - Development of cardiac safety translational tools for QT prolongation and torsade
      de pointes.
AB  - OBJECTIVE: A regulatory science priority at the Food and Drug Administration
      (FDA) is to promote the development of new innovative tools such as reliable and
      validated computational (in silico) models. This FDA Critical Path Initiative
      project involved the development of predictive clinical computational models for
      decision-support in CDER evaluations of QT/QTc interval prolongation and
      proarrhythmic potential for non-antiarrhythmic drugs. METHODS: Several
      classification models were built using predictive technologies of quantitative
      structure-activity relationship analysis using clinical in-house and public data
      on induction of QT prolongation and torsade de pointes (TdP) in humans. Specific
      models were geared toward prediction of high-risk drugs with attention to
      outcomes from thorough QT studies and TdP risk based on clinical in-house data.
      Models used were independent of non-clinical data or known molecular mechanisms.
      The positive predictive performance of the in silico models was validated using
      cross-validation and independent external validation test sets. RESULTS: Optimal
      performance was observed with high sensitivity (87%) and high specificity (88%)
      for predicting QT interval prolongation using in-house data, and 77% sensitivity
      in predicting drugs withdrawn from the market. Furthermore, the article describes
      alerting substructural features based on drugs tested in the clinical trials.
      CONCLUSIONS: The in silico models provide evidence of a structure-based
      explanation for these cardiac safety endpoints. The models will be made
      publically available and are under continual prospective external validation
      testing and updating at CDER using TQT study outcomes.

PMID- 23537165
TI  - Efficient delivery of cell impermeable phosphopeptides by a cyclic peptide
      amphiphile containing tryptophan and arginine.
AB  - Phosphopeptides are valuable reagent probes for studying protein-protein and
      protein-ligand interactions. The cellular delivery of phosphopeptides is
      challenging because of the presence of the negatively charged phosphate group.
      The cellular uptake of a number of fluorescent-labeled phosphopeptides, including
      F'-GpYLPQTV, F'-NEpYTARQ, F'-AEEEIYGEFEAKKKK, F'-PEpYLGLD, F'-pYVNVQN-NH2, and F'
      GpYEEI (F' = fluorescein), was evaluated in the presence or absence of a [WR]4, a
      cyclic peptide containing alternative arginine (R) and tryptophan (W) residues,
      in human leukemia cells (CCRF-CEM) after 2 h incubation using flow cytometry.
      [WR]4 improved significantly the cellular uptake of all phosphopeptides. PEpYLGLD
      is a sequence that mimics the pTyr1246 of ErbB2 that is responsible for binding
      to the Chk SH2 domain. The cellular uptake of F'-PEpYLGLD was enhanced
      dramatically by 27-fold in the presence of [WR]4 and was found to be time
      dependent. Confocal microscopy of a mixture of F'-PEpYLGLD and [WR]4 in live
      cells exhibited intracellular localization and significantly higher cellular
      uptake compared to that of F'-PEpYLGLD alone. Transmission electron microscopy
      (TEM) and isothermal calorimetry (ITC) were used to study the interaction of
      PEpYLGLD and [WR]4. TEM results showed that the mixture of PEpYLGLD and [WR]4
      formed noncircular nanosized structures with width and height of 125 and 60 nm,
      respectively. ITC binding studies confirmed the interaction between [WR]4 and
      PEpYLGLD. The binding isotherm curves, derived from sequential binding models,
      showed an exothermic interaction driven by entropy. These studies suggest that
      amphiphilic peptide [WR]4 can be used as a cellular delivery tool of cell
      impermeable negatively charged phosphopeptides.

PMID- 23537166
TI  - Temperature dependence and energetics of single ions at the aqueous liquid-vapor
      interface.
AB  - We investigate temperature-dependence of free energetics with two single halide
      anions, I(-) and Cl(-), crossing the aqueous liquid-vapor interface through
      molecular dynamics simulations. The result shows that I(-) has a modest surface
      stability of 0.5 kcal/mol at 300 K and the stability decreases as the temperature
      increases, indicating the surface adsorption process for the anion is
      entropically disfavored. In contrast, Cl(-) shows no such surface state at all
      temperatures. Decomposition of free energetics reveals that water-water
      interactions provide a favorable enthalpic contribution, while the desolvation of
      ion induces an increase in free energy. Calculations of surface fluctuations
      demonstrate that I(-) generates significantly greater interfacial fluctuations
      compared to Cl(-). The fluctuation is attributed to the malleability of the
      solvation shells, which allows for more long-ranged perturbations and solvent
      density redistribution induced by I(-) as the anion approaches the liquid-vapor
      interface. The increase in temperature of the solvent enhances the inherent
      thermally excited fluctuations and consequently reduces the relative contribution
      from anion to surface fluctuations, which is consistent with the decrease in
      surface stability of I(-). Our results indicate a strong correlation with induced
      interfacial fluctuations and anion surface stability; moreover, resulting
      temperature dependent behavior of induced fluctuations suggests the possibility
      of a critical level of induced fluctuations associated with surface stability.

PMID- 23537167
TI  - Computational purification of individual tumor gene expression profiles leads to
      significant improvements in prognostic prediction.
AB  - Tumor heterogeneity is a limiting factor in cancer treatment and in the discovery
      of biomarkers to personalize it. We describe a computational purification tool,
      ISOpure, to directly address the effects of variable normal tissue contamination
      in clinical tumor specimens. ISOpure uses a set of tumor expression profiles and
      a panel of healthy tissue expression profiles to generate a purified cancer
      profile for each tumor sample and an estimate of the proportion of RNA
      originating from cancerous cells. Applying ISOpure before identifying gene
      signatures leads to significant improvements in the prediction of prognosis and
      other clinical variables in lung and prostate cancer. 

PMID- 23537168
TI  - Diversity of culturable bacteria including Pantoea in wild mosquito Aedes
      albopictus.
AB  - BACKGROUND: The microbiota has been shown to play an important role in the
      biology of insects. In recent decades, significant efforts have been made to
      better understand the diversity of symbiotic bacteria associated with mosquitoes
      and assess their influence on pathogen transmission. Here, we report the
      bacterial composition found in field-caught Aedes albopictus populations by using
      culture-dependent methods. RESULTS: A total of 104 mosquito imagos (56 males and
      48 females) were caught from four contrasting biotopes of Madagascar and their
      bacterial contents were screened by plating whole body homogenates on three
      different culture media. From 281 bacterial colony types obtained, amplified
      ribosomal DNA restriction analysis (ARDRA) showed they had 40 distinct ribotypes.
      Sequencing and BLAST analysis of the 16S rDNA genes responsible for each
      representative profile made it possible to identify 27 genera distributed in
      three major phyla. In female mosquitoes, bacterial isolates were mostly
      Proteobacteria (51.3%) followed by Firmicutes (30.3%) and Actinobacteria (18.4%).
      Conversely, Actinobacteria was the most abundant phylum in male mosquitoes (48%)
      followed by Proteobacteria (30.6%) and Firmicutes (20.4%). The relative abundance
      and composition of isolates also varied between sampling sites, ranging from 3
      distinct families in Ankazobe to 8 in Tsimbazaza Park, and Toamasina and
      Ambohidratrimo. Pantoea was the most common genus in both females and males from
      all sampling sites, except for Ambohidratrimo. No differences in genome size were
      found between Pantoea isolates from mosquitoes and reference strains in pulse
      field gel electrophoresis. However, according to the numbers and sizes of
      plasmids, mosquito isolates clustered into three different groups with other
      strains isolated from insects but distinct from isolates from the environment.
      CONCLUSIONS: The recent upsurge in research into the functional role of the
      insect microbiota prompts the interest to better explore the role some bacteria
      detected here may have in the mosquito biology. Future studies of culturable
      bacteria might decipher whether they have a biological role in the invasiveness
      of Ae. albopictus. As a possible candidate for paratransgenesis, the predominant
      genus Pantoea will be characterized to better understand its genetic contents and
      any possible influence it may have on vector competence of Ae. albopictus.

PMID- 23537169
TI  - Effects of sweet cassava polysaccharide extracts on endurance exercise in rats.
AB  - BACKGROUND: Sweet cassava tubers have abundant carbohydrates consisting of
      monosaccharides and polysaccharides. In addition, polysaccharides extracted from
      plants improve sports performance, according to recent studies. We therefore
      examined whether the administration of sweet cassava polysaccharides (SCPs)
      benefited endurance performance in rats METHODS: Male Sprague-Dawley rats (n =
      30, 7 weeks old) were divided into three groups: control (C), exercise (Ex), and
      exercise plus SCPs administration (ExSCP) (at a dose of 500 mg/kg body weight by
      gastric intubation for six days in addition to standard rat food and water). An
      exercise program was implemented in the Ex and ExSCP groups for five days (with
      no exercise on the sixth day), and then all rats were sacrificed to determine the
      glycogen content of the gastrocnemius and soleus muscles, and the blood
      metabolites after the ExSCP and Ex groups had completed exhaustive running.
      RESULTS: The running time to exhaustion of the ExSCP group was significantly
      longer than that of the Ex group by 49% (64 vs. 43 min). After running to
      exhaustion, it was seen that although the glycogen content in the soleus and
      gastrocnemius muscles of the Ex and ExSCP groups was lower compared to the C
      group, values in the ExSCP group were significantly higher than in the Ex group
      (p > 0.05). In addition, blood glucose and free fatty acid (FFA) levels were
      significantly higher in the ExSCP than in the Ex group (p > 0.05). However, no
      significant differences for blood glucose or FFA were found between the ExSCP and
      C groups. CONCLUSIONS: SCP supplementation can prolong exercise endurance in
      rats. Higher muscle glycogen levels and stable glucose and FFA concentrations in
      the circulation contributed to the prolonged time to exhaustion.

PMID- 23537171
TI  - Analysis of public responses to preparedness policies: the cases of H1N1
      influenza vaccination and gas mask distribution.
AB  - BACKGROUND: During several months in 2009-2010, the Israeli population was asked
      to take part in two preparedness programs: Acquisition of gas masks against a
      potential chemical-warfare attack, and vaccination against the A/H1N1 influenza
      pandemics. Compliance with the first request was moderate and did not attract
      much attention, whereas compliance with the second request was very low and was
      accompanied by significant controversy. The aims of this study are to compare the
      public's attitudes towards these two preparedness campaigns, and to explore the
      roles of trust, reasoned assessment, and reflexive reactions in the public's
      response to governmental preparedness policies. METHODS: The comparative analysis
      was based on a telephone survey of 2,018 respondents representing a cross-section
      of the adult Israeli population. Univariate analysis to describe associations of
      public response and attitude was performed by Chi-square tests. FINDINGS: A set
      of queries related to actual compliance, trust in credibility of authorities,
      personal opinions, reasons for non-compliance, and attitudes towards
      uncertainties was used to characterize the response to mask-acquisition and
      vaccination. In the case of mask-acquisition, the dominant response profile was
      of trusting compliance based on non-conditional belief in the need to adhere to
      the recommendation (35.6% of respondents). In the case of vaccination, the
      dominant response profile was of trusting non-compliance based on a reflective
      belief in the need for adherence (34.8% of respondents). Among the variables
      examined in the study, passivity was found to be the major reason for non
      compliance with mask-acquisition, whereas reasoned assessment of risk played a
      major role in non-compliance with vaccination. Realization of the complexity in
      dealing with uncertainty related to developing epidemics and to newly-developed
      vaccines was identified in the public's response to the H1N1 vaccination
      campaign. CONCLUSIONS: The newly identified profile of "trusting-reflective-non
      complier" individuals should be of concern to policy makers. The public is not
      accepting governmental recommendations in an unconditional manner. This is not
      driven by lack of trust in authorities, but rather by the perception of the
      responsibility of individuals in confronting forthcoming risks. Nevertheless,
      under certain conditions the public may respond in a non-reflective way and
      delegate this responsibly to authorities in an uncontested manner. This leaves
      the policy makers with the complex challenge of interacting with a passive non
      involved public or alternatively with an opinionated, reflexive public.

PMID- 23537170
TI  - Genetic diversity and signatures of selection of drug resistance in Plasmodium
      populations from both human and mosquito hosts in continental Equatorial Guinea.
AB  - BACKGROUND: In Plasmodium, the high level of genetic diversity and the
      interactions established by co-infecting parasite populations within the same
      host may be a source of selection on pathogen virulence and drug resistance. As
      different patterns have already been described in humans and mosquitoes, parasite
      diversity and population structure should be studied in both hosts to properly
      assess their effects on infection and transmission dynamics. This study aimed to
      characterize the circulating populations of Plasmodium spp and Plasmodium
      falciparum from a combined set of human blood and mosquito samples gathered in
      mainland Equatorial Guinea. Further, the origin and evolution of anti-malarial
      resistance in this area, where malaria remains a major public health problem were
      traced. METHODS: Plasmodium species infecting humans and mosquitoes were
      identified by nested-PCR of chelex-extracted DNA from dried blood spot samples
      and mosquitoes. Analysis of Pfmsp2 gene, anti-malarial-resistance associated
      genes, Pfdhps, Pfdhfr, Pfcrt and Pfmdr1, neutral microsatellites (STR) loci and
      Pfdhfr and Pfdhps flanking STR was undertaken to evaluate P. falciparum
      diversity. RESULTS: Prevalence of infection remains high in mainland Equatorial
      Guinea. No differences in parasite formula or significant genetic differentiation
      were seen in the parasite populations in both human and mosquito samples. Point
      mutations in all genes associated with anti-malarial resistance were highly
      prevalent. A high prevalence was observed for the Pfdhfr triple mutant in
      particular, associated with pyrimethamine resistance.Analysis of Pfdhps and
      Pfdhfr flanking STR revealed a decrease in the genetic diversity. This finding
      along with multiple independent introductions of Pfdhps mutant haplotypes suggest
      a soft selective sweep and an increased differentiation at Pfdhfr flanking
      microsatellites hints a model of positive directional selection for this gene.
      CONCLUSIONS: Chloroquine is no longer recommended for malaria treatment in
      Equatorial Guinea but sulphadoxine-pyrimethamine (SP) remains in use in
      combination with artesunate and is the only drug recommended in preventive
      chemotherapy in pregnancy. The high prevalence of point mutations in Pfdhfr and
      Pfdhps points to the danger of an eventual reduction in the efficacy of SP
      combined therapy in P. falciparum populations in Equatorial Guinea and to the
      essential continuous monitoring of these two genes.

PMID- 23537172
TI  - Factors affecting the use of prenatal care by non-western women in industrialized
      western countries: a systematic review.
AB  - BACKGROUND: Despite the potential of prenatal care for addressing many pregnancy
      complications and concurrent health problems, non-western women in industrialized
      western countries more often make inadequate use of prenatal care than women from
      the majority population do. This study aimed to give a systematic review of
      factors affecting non-western women's use of prenatal care (both medical care and
      prenatal classes) in industrialized western countries. METHODS: Eleven databases
      (PubMed, Embase, PsycINFO, Cochrane, Sociological Abstracts, Web of Science,
      Women's Studies International, MIDIRS, CINAHL, Scopus and the NIVEL catalogue)
      were searched for relevant peer-reviewed articles from between 1995 and July
      2012. Qualitative as well as quantitative studies were included. Quality was
      assessed using the Mixed Methods Appraisal Tool. Factors identified were
      classified as impeding or facilitating, and categorized according to a conceptual
      framework, an elaborated version of Andersen's healthcare utilization model.
      RESULTS: Sixteen articles provided relevant factors that were all categorized. A
      number of factors (migration, culture, position in host country, social network,
      expertise of the care provider and personal treatment and communication) were
      found to include both facilitating and impeding factors for non-western women's
      utilization of prenatal care. The category demographic, genetic and pregnancy
      characteristics and the category accessibility of care only included impeding
      factors.Lack of knowledge of the western healthcare system and poor language
      proficiency were the most frequently reported impeding factors. Provision of
      information and care in women's native languages was the most frequently reported
      facilitating factor. CONCLUSION: The factors found in this review provide
      specific indications for identifying non-western women who are at risk of not
      using prenatal care adequately and for developing interventions and appropriate
      policy aimed at improving their prenatal care utilization.

PMID- 23537173
TI  - Effects of photoaging information and UV photo on sun protection intentions and
      behaviours: a cross-regional comparison.
AB  - There is limited empirical evidence regarding differences in sun protection
      practices in different regions of the USA. This study examined whether there are
      regional differences in the efficacy of exposure to UV photographs and photoaging
      information (e.g. wrinkles and age spots) for increasing sun protection
      behaviours. Students attending a public university in either the Midwestern
      (Iowa) or Southwestern (Southern California) US reported baseline sun exposure
      and protection practices and were then randomly assigned to either receive
      information about photoaging, have a UV photo taken, both receive photoaging
      information and have a UV photo taken, or to receive neither intervention. Sun
      protection intentions were assessed immediately after the interventions, and both
      self-reported sun protection behaviours and an objective assessment (via
      spectrophotometry) of skin colour change were measured at the end of summer and
      one year following the interventions. The results showed a pervasive pattern of
      more risky UV exposure and less sun protection use at the Iowa site than at the
      Southern California site both prior to and following the interventions. Both
      interventions increased future sun protection intentions regardless of region.
      However, the intervention effects on skin colour and UV exposure differed across
      region, with generally more reliable effects at the Iowa site. 

PMID- 23537174
TI  - Metabolic and toxicological considerations of the opioid replacement therapy and
      analgesic drugs: methadone and buprenorphine.
AB  - INTRODUCTION: Methadone and buprenorphine are maintenance replacement therapies
      for opioid dependence; they are also used for pain management. Methadone and
      buprenorphine (to a lesser extent) have seen sharp increases in mortality
      associated with their use. They have distinct routes of metabolism (mostly
      cytochrome P450 dependent), and distinct pharmacologic activity of metabolites.
      As such, metabolism may play a role in differences in their toxicity. AREAS
      COVERED: This article reviews peer-reviewed literature obtained from PubMed
      searches and literature referenced within. The review considers first an overview
      of drug use and mortality over the past decade. It then provides extensive detail
      on the in vitro and in vivo human metabolism of methadone and buprenorphine.
      Using both human and experimental animal studies it then presents the
      pharmacodynamic activity of parent drug and metabolites at the mu-opioid
      receptor, as P-glycoprotein substrates and plasma/brain concentration ratios, and
      activity at the hERG K(+) channel. Lessons learned from drug interaction studies
      in humans are then examined in an attempt to bring together the combined
      information. EXPERT OPINION: The use and misuse of these drugs contributes to the
      epidemic in opioid-associated mortalities. A better understanding of metabolism-,
      transport- and co-medication-induced changes will contribute to their safer use.

PMID- 23537176
TI  - A demonstration of the antimicrobial effectiveness of various copper surfaces.
AB  - BACKGROUND: Bacterial contamination on touch surfaces results in increased risk
      of infection. In the last few decades, work has been done on the antimicrobial
      properties of copper and its alloys against a range of micro-organisms
      threatening public health in food processing, healthcare and air conditioning
      applications; however, an optimum copper method of surface deposition and mass
      structure has not been identified. RESULTS: A proof-of-concept study of the
      disinfection effectiveness of three copper surfaces was performed. The surfaces
      were produced by the deposition of copper using three methods of thermal spray,
      namely, plasma spray, wire arc spray and cold spray The surfaces were then
      inoculated with meticillin-resistant Staphylococcus aureus (MRSA). After a two
      hour exposure to the surfaces, the surviving MRSA were assayed and the results
      compared.The differences in the copper depositions produced by the three thermal
      spray methods were examined in order to explain the mechanism that causes the
      observed differences in MRSA killing efficiencies. The cold spray deposition
      method was significantly more effective than the other methods. It was determined
      that work hardening caused by the high velocity particle impacts created by the
      cold spray technique results in a copper microstructure that enhances ionic
      diffusion, and copper ions are principally responsible for antimicrobial
      activity. CONCLUSIONS: This test showed significant microbiologic differences
      between coatings produced by different spray techniques and demonstrates the
      importance of the copper application technique. The cold spray technique shows
      superior anti-microbial effectiveness caused by the high impact velocity imparted
      to the sprayed particles which results in high dislocation density and high ionic
      diffusivity.

PMID- 23537175
TI  - Kinetics of the porcine reproductive and respiratory syndrome virus (PRRSV)
      humoral immune response in swine serum and oral fluids collected from individual
      boars.
AB  - BACKGROUND: The object of this study was to describe and contrast the kinetics of
      the humoral response in serum and oral fluid specimens during acute porcine
      reproductive and respiratory syndrome virus (PRRSV) infection. The study involved
      three trials of 24 boars each. Boars were intramuscularly inoculated with a
      commercial modified live virus (MLV) vaccine (Trial 1), a Type 1 PRRSV field
      isolated (Trial 2), or a Type 2 PRRSV field isolate (Trial 3). Oral fluid samples
      were collected from individual boars on day post inoculation (DPI) -7 and 0 to
      21. Serum samples were collected from all boars on DPI -7, 0, 7, 14, 21 and from
      4 randomly selected boars on DPI 3, 5, 10, and 17. Thereafter, serum and oral
      fluid were assayed for PRRSV antibody using antibody isotype-specific ELISAs
      (IgM, IgA, IgG) adapted to serum or oral fluid. RESULTS: Statistically
      significant differences in viral replication and antibody responses were observed
      among the three trials in both serum and oral fluid specimens. PRRSV serum IgM,
      IgA, and IgG were first detected in samples collected on DPI 7, 10, and 10,
      respectively. Oral fluid IgM, IgA, and IgG were detected in samples collected
      between DPI 3 to 10, 7 to 10, and 8 to 14, respectively. CONCLUSIONS: This study
      enhanced our knowledge of the PRRSV humoral immune response and provided a
      broader foundation for the development and application of oral fluid antibody
      based diagnostics.

PMID- 23537177
TI  - American Academy of Periodontology statement on the use of moderate sedation by
      periodontists.

PMID- 23537178
TI  - Peri-implant mucositis and peri-implantitis: a current understanding of their
      diagnoses and clinical implications.

PMID- 23537179
TI  - Clarification/Erratum: The use of conscious sedation by periodontists.

PMID- 23537180
TI  - Clarification/Erratum: Guidelines: In-office use of conscious sedation in
      periodontics.

PMID- 23537182
TI  - Integrative taxonomy on the fast track - towards more sustainability in
      biodiversity research.
AB  - BACKGROUND: A so called "taxonomic impediment" has been recognized as a major
      obstacle to biodiversity research for the past two decades. Numerous remedies
      were then proposed. However, neither significant progress in terms of formal
      species descriptions, nor a minimum standard for descriptions have been achieved
      so far. Here, we analyze the problems of traditional taxonomy which often
      produces keys and descriptions of limited practical value. We suggest that
      phylogenetics and phenetics had a subtle and so far unnoticed effect on taxonomy
      leading to inflated species descriptions. DISCUSSION: The term "turbo-taxonomy"
      was recently coined for an approach combining cox1 sequences, concise
      morphological descriptions by an expert taxonomist, and high-resolution digital
      imaging to streamline the formal description of larger numbers of new species. We
      propose a further development of this approach which, together with open access
      web-publication and automated pushing of content from journal into a wiki, may
      create the most efficient and sustainable way to conduct taxonomy in the future.
      On demand, highly concise descriptions can be gradually updated or modified in
      the fully versioned wiki-framework we use. This means that the visibility of
      additional data is not compromised, while the original species description -the
      first version- remains preserved in the wiki, and of course in the journal
      version. A DNA sequence database with an identification engine replaces an
      identification key, helps to avoid synonyms and has the potential to detect
      grossly incorrect generic placements. We demonstrate the functionality of a
      species-description pipeline by naming 101 new species of hyperdiverse New Guinea
      Trigonopterus weevils in the open-access journal ZooKeys. SUMMARY: Fast track
      taxonomy will not only increase speed, but also sustainability of global species
      inventories. It will be of great practical value to all the other disciplines
      that depend on a usable taxonomy and will change our perception of global
      biodiversity. While this approach is certainly not suitable for all taxa alike,
      it is the tool that will help to tackle many hyperdiverse groups and pave the
      road for more sustainable comparative studies, e.g. in community ecology,
      phylogeography and large scale biogeographic studies.

PMID- 23537181
TI  - Diversity of endophytic fungi and screening of fungal paclitaxel producer from
      Anglojap yew, Taxus x media.
AB  - BACKGROUND: Endophytic fungi represent underexplored resource of novel lead
      compounds and have a capacity to produce diverse class of plant secondary
      metabolites. Here we investigated endophytic fungi diversity and screening of
      paclitaxel-producing fungi from Taxus x media. RESULTS: Eighty-one endophytic
      fungi isolated from T. media were grouped into 8 genera based on the
      morphological and molecular identification. Guignardia and Colletotrichum were
      the dominant genera, whereas the remaining genera were infrequent groups. The
      genera Glomerella and Gibberella were first reported in Taxus. Three
      representative species of the distinct genera gave positive hits by molecular
      marker screening and were capable of producing taxol which were validated by HPLC
      MS. Among these 3 taxol-producing fungi, the highest yield of taxol was 720 ng/l
      by Guignardia mangiferae HAA11 compared with those of Fusarium proliferatum HBA29
      (240 ng/l) and Colletotrichum gloeosporioides TA67 (120 ng/l). This is the first
      report of taxol producer from Guignardia. Moreover, the lower similarities of ts
      and bapt between microbial and plant origin suggested that fungal taxol
      biosynthetic cluster might be repeatedly invented during evolution, nor
      horizontal gene transfer from Taxus species. CONCLUSIONS: Taxol-producing
      endophytic fungi could be a fascinating reservoir to generate taxol-related drug
      lead and to elucidate the remained 5 unknown genes or the potential regulation
      mechanism in the taxol biosynthesis pathway.

PMID- 23537183
TI  - Molecular dynamics simulations of CO2 and brine interfacial tension at high
      temperatures and pressures.
AB  - Molecular dynamics simulations have been performed to study the interfacial
      tension of CO2 and brine for a range of temperatures between 303 and 393 K and
      pressures from 2 to 50 MPa. The ions involved in this study are Na(+), Ca(2+),
      and Cl(-). The results indicate that the interfacial tension decreases with
      increasing pressure under any temperature condition but increases linearly with
      the molality of the salt solution. The density profiles calculated from the MD
      simulation results also indicate a positive excess of CO2 and a negative excess
      of ions at the interface. The charge of the ions was found to have a larger
      influence than their size on the interfacial tension, a result that consistent
      with experimental findings.

PMID- 23537184
TI  - Using amino acid factor scores to predict avian-to-human transmission of avian
      influenza viruses: a machine learning study.
AB  - In this study, the problem of predicting interspecies transmission of avian
      influenza viruses (AIVs) was investigated with machine learning methods. We
      identified 87 signature positions in AIV protein sequences with information
      entropy method and encoded these positions with five amino acid factor scores
      (AAFactors) concentrated from 491 physicochemical and biochemical properties of
      amino acids. We constructed four prediction models by integrating these five
      features with commonly used machine learning technologies including Decision
      Tree, Naive Bayes, Random Forest and Support Vector Machine. The cross validation
      experiment results demonstrated the power of AAFactors in predicting avian-to
      human transmission of AIVs. Comparative analysis revealed the strengths and
      weaknesses of different machine learning methods, and the importance of different
      AAFactors to the prediction.

PMID- 23537185
TI  - Prediction of Brugia malayi antigenic peptides: candidates for synthetic vaccine
      design against lymphatic filariasis.
AB  - Brugia malayi is a threadlike nematode cause's swelling of lymphatic organs,
      condition well known as lymphatic filariasis; till date no invention made to
      effectively address lymphatic filariasis. In this analysis we a have predicted
      suitable antigenic peptides from Brugia malayi antigen protein for peptide
      vaccine design against lymphatic filariasis based on cross protection phenomenon
      as, an ample immune response can be generated with a single protein subunit. We
      found MHC class II binding peptides of Brugia malayi antigen protein are
      important determinant against the diseased condition. The analysis shows Brugia
      malayi antigen protein having 505 amino acids, which shows 497 nonamers. In this
      assay, we have predicted MHC-I binding peptides for 8mer_H2_Db (optimal score-
      15.966), 9mer_H2_Db (optimal score- 15.595), 10mer_H2_Db (optimal score- 19.405),
      11mer_H2_Dballeles (optimal score- 23.801). We also predicted the SVM based MHCII
      IAb nonamers, 51-FQQIDPLDA, 442-FAAIACLVH, 206-YLNPFGHQF, 167-WYVIMAACY, 367
      YAMIVIRLL, 434- LVITTAANF, 176-LDSYCLWKP, 435-VITTAANFA, 364-WPGYAMIVI (optimal
      score- 13.963); MHCII-IAd nonamers, 52-QQIDPLDAE, 171-MAACYLDSY, 239-QWRSVILCN,
      168-YVIMAACYL, 3-QYLSVHSLS, 322-EILLHAKVV, 417- LGIIASFVS, 396-KAIFLAHFG, 167
      WYVIMAACY, 269-LALHCINVI, 93-FINKAAPKQ, 259-NCIIVLKAF, 79- QGVLLIIPR, 22
      TILQRSQAI, 63-RGFVYGNVS, 109-NISSLAFET,(optimal score- 16.748); and MHCII-IAg7
      nonamers 171-MAACYLDSY, 73-KIVNGAQGV, 259-NCIIVLKAF, 209-PFGHQFSFE, 102
      SCDTLLKNI, 25-QRSQAIRIV, 444- AIACLVHLF, 88-SLVNGFINK, 252-FPRHQLLNC, 471
      RFVLANDNE, 52-QQIDPLDAE, 469-HRRFVLAND, 457- SNRHYFLAD, 362-KSWPGYAMI, 476
      NDNEGEDFE, 370-IVIRLLQAL (optimal score- 19.847) which represents potential
      binders from Brugia malayi antigen protein. The method integrates prediction of
      MHC class I binding proteasomal C-terminal cleavage peptides and Eighteen
      potential antigenic peptides at average propensity 1.063 having highest local
      hydrophilicity. Thus a small antigen fragment can induce immune response against
      whole antigen. This approach can be applied for designing subunit and synthetic
      peptide vaccines.

PMID- 23537186
TI  - Measuring the effectiveness of an intensive IPV training program offered to Greek
      general practitioners and residents of general practice.
AB  - BACKGROUND: The need for effective training of primary care physicians in the
      prevention, detection and handling of intimate partner violence (IPV) has been
      widely acknowledged, given its frequency in daily practice. The current
      intervention study aimed to measure changes in the actual IPV knowledge,
      perceived knowledge, perceived preparedness and detection ability of practicing
      general practitioners (GPs) and general practice residents, following an
      intensive IPV training program. METHODS: A pre/post-test design with a control
      group was employed to compare changes in baseline measures of IPV at the post
      intervention stage and at 12 months. A total of 40 participants provided full
      data; 25 GPs (11 in the intervention and 14 in the control) and 15 residents
      (intervention only). Three scales of the PREMIS survey were used to draw
      information on the study outcomes. RESULTS: The training program met high
      acceptance by both groups of participants and high practicality in clinical
      practice. The GPs in the intervention group performed better than the GPs in the
      control group on "Perceived preparedness" and "Perceived knowledge" in both the
      post-intervention (p= .012, r= .50 and p= .001, r= .68) and the 12-month follow
      up (p= .024, r= .45 and p= .007, r= .54) as well as better than the residents in
      "Perceived preparedness" at post-intervention level (p= .037, r= .41). Residents
      on the other hand, performed better than the GPs in the intervention group on
      "Actual knowledge" at the 12-month follow-up (p= .012, r= .49). No significant
      improvements or between group differences were found in terms of the self
      reported detection of IPV cases. CONCLUSION: Further studies are needed to decide
      whether residency training could serve as an early intervention stage for IPV
      training.

PMID- 23537187
TI  - Manual blood exchange transfusion does not significantly contribute to parasite
      clearance in artesunate-treated individuals with imported severe Plasmodium
      falciparum malaria.
AB  - BACKGROUND: Exchange transfusion (ET) has remained a controversial adjunct
      therapy for the treatment of severe malaria. In order to assess the relative
      contribution of ET to parasite clearance in severe malaria, all patients
      receiving ET as an adjunct treatment to parenteral quinine or to artesunate were
      compared with patients treated with parenteral treatment with quinine or
      artesunate but who did not receive ET. ET was executed using a standardized
      manual isovolumetric exchange protocol. METHODS: All patients in the Rotterdam
      Malaria Cohort treated for severe P. falciparum malaria at the Institute for
      Tropical Diseases of the Harbour Hospital between 1999 and 2011 were included in
      this retrospective follow-up study. Both a two-stage approach and a log-linear
      mixed model approach were used to estimate parasite clearance times (PCTs) in
      patients with imported malaria. Severe malaria was defined according to WHO
      criteria. RESULTS: A total of 87 patients with severe malaria was included; 61
      received intravenous quinine, whereas 26 patients received intravenous
      artesunate. Thirty-nine patients received ET as an adjunct treatment to either
      quinine (n = 23) or artesunate (n = 16). Data from 84 of 87 patients were
      suitable for estimation of parasite clearance rates. PCTs were significantly
      shorter after administration of artesunate as compared with quinine. In both
      models, ET did not contribute significantly to overall parasite clearance.
      CONCLUSION: Manual exchange transfusion does not significantly contribute to
      parasite clearance in artesunate-treated individuals. There may be a small effect
      of ET on parasite clearance under quinine treatment. Institution of ET to promote
      parasite clearance in settings where artesunate is available is not recommended,
      at least not with manually executed exchange procedures.

PMID- 23537188
TI  - Is a perceived supportive physical environment important for self-reported
      leisure time physical activity among socioeconomically disadvantaged women with
      poor psychosocial characteristics? An observational study.
AB  - BACKGROUND: Over the past decade, studies and public health interventions that
      target the physical environment as an avenue for promoting physical activity have
      increased in number. While it appears that a supportive physical environment has
      a role to play in promoting physical activity, social-ecological models emphasise
      the importance of considering other multiple levels of influence on behaviour,
      including individual (e.g. self-efficacy, intentions, enjoyment) and social (e.g.
      social support, access to childcare) factors (psychosocial factors). However, not
      everyone has these physical activity-promoting psychosocial characteristics; it
      remains unclear what contribution the environment makes to physical activity
      among these groups. This study aimed to examine the association between the
      perceived physical environment and self-reported leisure-time physical activity
      (LTPA) among women living in socioeconomically disadvantaged areas demonstrating
      different psychosocial characteristics. METHODS: In 2007-8, 3765 women (18-45
      years) randomly selected from low socioeconomic areas in Victoria, Australia,
      self-reported LTPA, and individual, social and physical environmental factors
      hypothesised within a social-ecological framework to influence LTPA. Psychosocial
      and environment scores were created. Associations between environment scores and
      categories of LTPA (overall and stratified by thirds of perceived environment
      scores) were examined using generalised ordered logistic regression. RESULTS:
      Women with medium and high perceived environment scores had 20-38% and 44-70%
      greater odds respectively of achieving higher levels of LTPA than women with low
      environment scores. When stratified by thirds of psychosocial factor scores,
      these associations were largely attenuated and mostly became non-significant.
      However, women with the lowest psychosocial scores but medium or high environment
      scores had 76% and 58% higher odds respectively of achieving >=120 minutes/week
      (vs. <120 minutes/week) LTPA. CONCLUSIONS: Acknowledging the cross-sectional
      study design, the findings suggest that a physical environment perceived to be
      supportive of physical activity might help women with less favourable
      psychosocial characteristics achieve moderate amounts of LTPA (i.e. >=120
      minutes/week). This study provides further support for research and public health
      interventions to target perceptions of the physical environment as a key
      component of strategies to promote physical activity.

PMID- 23537189
TI  - Antegrade percutaneous flexible endoscopic approach for the management of urinary
      diversion-associated complications.
AB  - PURPOSE: We present our experience in the minimally invasive management of
      postoperative complications associated with urinary diversions using an ureteral
      access sheath (UAS) in an antegrade approach. PATIENTS AND METHODS: From 2005 to
      2011, 21 antegrade flexible ureteroscopies (F-URS) were performed in 17 patients
      with a urinary diversion. Urinary diversions in this population consisted of
      ileal conduits, orthotopic neobladders, catheterizable pouches, and an
      ureterosigmoidostomy in 9, 5, 2, and 1 patients, respectively. The most important
      reason for treatment was recurrent upper urinary tract infection. The indication
      for intervention was stone disease in 15 procedures and strictures in 6 cases. In
      two patients, "staged-therapy" was performed. Using UAS in an antegrade approach
      was the main concept. RESULTS: A nephrostomy tube was already in place in 14
      (66.6%) procedures, which was the access route used. Successful puncture was
      performed in all other patients. Eighty percent of patients were rendered stone
      free after the first antegrade session. Moreover, all strictures were
      successfully managed by dilation. In two sequential procedures in a patient,
      there was an inability to perform stone treatment because of abnormal position of
      the ureter (kinked), which did not allow the ureterorenoscope to pass. All other
      procedures were uneventful. Postoperative complications were reported in four
      procedures. There was significant urinary tract infection in two patients as well
      as an obstructed nephrostomy tube in two patients. CONCLUSION: An antegrade
      endoscopic procedure using UAS in patients who present with stones or
      ureterointestinal stricture as late complications of urinary diversion is a
      feasible, well-tolerated technique, especially when using smaller access sheaths.

PMID- 23537190
TI  - Information giving and involvement in treatment decisions: is more really better?
      Psychological effects and relation with adherence.
AB  - OBJECTIVES: The aim of this study is to improve our understanding of the ways in
      which a medical consultation style relates to satisfaction and adherence. DESIGN:
      Participants completed questionnaires about preferred and perceived consultation
      styles; psychological variables such as satisfaction, anxiety and depression; and
      questions about taking medication. Questionnaires were completed prior to the
      consultation, immediately after, three months later and one year later. Doctors
      also completed a scale on completion of the consultation. The decisions in
      question related to women seeking advice about Hormone Replacement Therapy (HRT)
      and decisions about pain management. RESULTS: Patients expressed preferences for
      information about the treatment options and for active involvement in the
      decision process. The extent to which patients perceived themselves as having
      received information about the treatment options was a particularly consistent
      predictor of satisfaction. The extent to which patients perceived themselves as
      having been prepared for the side effects of HRT was a consistent predictor of
      anxiety. CONCLUSIONS: Perceptions of the amount of information received about
      medical options, including information preparing individuals for potential side
      effects of medication, appears to be more important to satisfaction and anxiety,
      than actual involvement in the decision.

PMID- 23537191
TI  - Inhaler devices for patients with COPD.
AB  - Chronic obstructive pulmonary disease (COPD) continues to be associated with
      increased morbidity and mortality risk in spite of updated guidelines and a
      better understanding of this condition. Progressive airflow limitation and
      resultant hyperinflation-the respiratory hallmarks of this complex and often
      under-diagnosed disease-can be treated with pharmacotherapies emitted via
      nebulizers, pressurized metered-dose inhalers, dry powder inhalers, or a Soft
      Mist inhaler. Pharmaceutical company proprietary issues, technological
      innovations, and societal pressure have expanded the list of available inhalers,
      with a limited range of medications available for any one device. Each device has
      different operating and maintenance instructions, and successful use of a given
      drug/device combination requires that patients understand, maintain, and use each
      of their devices properly in order to ensure consistent and optimal pulmonary
      drug delivery. Clinicians are faced with a range of physical and psychosocial
      issues unique to each patient with COPD that must be overcome in order to match a
      suitable inhaler to the individual. Improved drug delivery afforded by next
      generation inhalers, coupled with an awareness of device-specific and patient
      specific variables affecting inhaler use, may improve clinical outcomes in the
      treatment of COPD.

PMID- 23537193
TI  - Lu3+/Yb3+ and Lu3+/Er3+ co-doped antimony selenide nanomaterials: synthesis,
      characterization, and electrical, thermoelectrical, and optical properties.
AB  - Lu3+/Yb3+ and Lu3+/Er3+ co-doped Sb2Se3 nanomaterials were synthesized by co
      reduction method in hydrothermal condition. Powder X-ray diffraction patterns
      indicate that the LnxLn'xSb2-2xSe3 Ln: Lu3+/Yb3+ and Lu3+/Er3+ crystals (x = 0.00
      - 0.04) are isostructural with Sb2Se3. The cell parameters were increased for
      compounds upon increasing the dopant content (x). Scanning electron microscopy
      and transmission electron microscopy images show that co-doping of Lu3+/Yb3+ ions
      in the lattice of Sb2Se3 produces nanorods, while that in Lu3+/Er3+ produces
      nanoparticles, respectively. The electrical conductivity of co-doped Sb2Se3 is
      higher than that of the pure Sb2Se3 and increases with temperature. By increasing
      the concentration of Ln3+ions, the absorption spectrum of Sb2Se3 shows red shifts
      and some intensity changes. In addition to the characteristic red emission peaks
      of Sb2Se3, emission spectra of co-doped materials show other emission bands
      originating from f-f transitions of the Yb3+ ions.

PMID- 23537192
TI  - Designing a theory-informed, contextually appropriate intervention strategy to
      improve delivery of paediatric services in Kenyan hospitals.
AB  - BACKGROUND: District hospital services in Kenya and many low-income countries
      should deliver proven, effective interventions that could substantially reduce
      child and newborn mortality. However such services are often of poor quality.
      Researchers have therefore been challenged to identify intervention strategies
      that go beyond addressing knowledge, skill, or resource inadequacies to support
      health systems to deliver better services at scale. An effort to develop a system
      oriented intervention tailored to local needs and context and drawing on theory
      is described. METHODS: An intervention was designed to improve district hospital
      services for children based on four main strategies: a reflective process to
      distill root causes for the observed problems with service delivery; developing a
      set of possible intervention approaches to address these problems; a search of
      literature for theory that provided the most appropriate basis for intervention
      design; and repeatedly moving backwards and forwards between identified causes,
      proposed interventions, identified theory, and knowledge of the existing context
      to develop an overarching intervention that seemed feasible and likely to be
      acceptable and potentially sustainable. RESULTS AND DISCUSSION: In addition to
      human and resource constraints key problems included failures of relevant
      professionals to take responsibility for or ownership of the challenge of
      pediatric service delivery; inadequately prepared, poorly supported leaders of
      service units (mid-level managers) who are often professionally and
      geographically isolated and an almost complete lack of useful information for
      routinely monitoring or understanding service delivery practice or outcomes. A
      system-oriented intervention recognizing the pivotal role of leaders of service
      units but addressing the outer and inner setting of hospitals was designed to
      help shape and support an appropriate role for these professionals. It aims to
      foster a sense of ownership while providing the necessary understanding,
      knowledge, and skills for mid-level managers to work effectively with senior
      managers and frontline staff to improve services. The intervention will include
      development of an information system, feedback mechanisms, and discussion fora
      that promote positive change. The vehicle for such an intervention is a
      collaborative network partnering government and national professional
      associations. This case is presented to promote discussion on approaches to
      developing context appropriate interventions particularly in international
      health.

PMID- 23537194
TI  - The challenges and rewards of engaging a skeptical public.
AB  - Findings published in this issue suggest that a substantial subset of the Israeli
      public generally trusts government, yet is determined to make their own judgments
      about the need for precautionary action in certain types of public health
      emergencies. This reflective approach, which may be common in other countries as
      well, poses a substantial challenge to achieving desired levels of compliance,
      particularly when the threat requires swift and concerted action. The aim of this
      commentary is to discuss both the challenges and the rewards of engaging a public
      that wants to weigh evidence prior to taking action in an emergency, rather than
      defer to expert judgment. While engaging a skeptical public can be difficult, a
      reflective public acknowledges that preparedness is a shared responsibility of
      government and individuals and may be receptive to messages about the need for
      household and community self-sufficiency in a disaster. This is a commentary on
      the article "Analysis of Public Responses to Preparedness Policies" by Velan and
      colleagues.

PMID- 23537195
TI  - Filial piety in palliative care: faithfully following family feelings. Or is it?

PMID- 23537196
TI  - An integrative review of sexual health issues in advanced incurable disease.
AB  - The sexual health needs of people with advanced incurable diseases are
      underexplored and under assessed by health care practitioners and under studied
      by researchers. The loss of sexual health can impact a person's overall quality
      of life and well-being. This integrative review of the literature presents the
      current state of the science and was conducted to identify and summarize
      publications in the professional literature related to the sexual health needs of
      people with advanced illness. A systematic search of 18 databases for studies
      conducted between 1960 and April 2012 in the English language that focused on the
      sexual health needs of people with life-limiting illnesses was conducted.
      Findings document that studies regarding the sexual health of patients with life
      limiting illnesses are generally narrative reviews, expert opinions, or
      exploratory in nature. Of the 30 possibly relevant abstracts and titles
      identified, there was only one prospective or case control trial focusing on
      sexual health in this population thereby offering the practitioner little
      research evidence to inform clinical practice. Increasing our understanding of
      the sexual health needs of people facing the end of their lives is crucial if we
      are to conduct appropriate assessments and initiate relevant treatments. Further
      prospective research is required to assess and establish the sexual health
      concerns of people along the disease trajectory of incurable illness as well as
      those imminently facing the end of their lives.

PMID- 23537198
TI  - In situ investigation of cathode and local biofilm microenvironments reveals
      important roles of OH- and oxygen transport in microbial fuel cells.
AB  - Mass transport within a cathode, including OH(-) transport and oxygen diffusion,
      is important for the performance of air-cathode microbial fuel cells (MFCs).
      However, little is known regarding how mass transport profiles are associated
      with MFC performance and how they are affected by biofilm that inevitably forms
      on the cathode surface. In this study, the OH(-) and oxygen profiles of a cathode
      biofilm were probed in situ in an MFC using microelectrodes. The pH of the
      catalyst layer interface increased from 7.0 +/- 0.1 to 9.4 +/- 0.3 in a buffered
      MFC with a bare cathode, which demonstrates significant accumulation of OH(-) in
      the cathode region. Furthermore, the pH of the interface increased to 10.0 +/-
      0.3 in the presence of the local biofilm, which indicates that OH(-) transport
      was severely blocked. As a result of the significant OH(-) accumulation, the
      maximum power density of the MFC decreased from 1.8 +/- 0.1 W/m(2) to 1.5 +/-
      0.08 W/m(2). In contrast, oxygen crossover, which was significant under low
      current flow conditions, was limited by the cathode biofilm. As a result of the
      blocked oxygen crossover, higher MFC coulombic efficiency (CE) was achieved in
      the presence of the cathode biofilm. These results indicate that enhanced OH(-)
      transport and decreased oxygen crossover would be beneficial for high-performance
      MFC development.

PMID- 23537197
TI  - Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with
      melanoma susceptibility in a Spanish population.
AB  - BACKGROUND: Few high penetrance genes are known in Malignant Melanoma (MM),
      however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP,
      SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS)
      have been the ideal strategy to identify new common, low-penetrance
      susceptibility loci. In this case-control study, we try to validate in our
      population nine melanoma associated markers selected from published GWAS in
      melanoma predisposition. METHODS: We genotyped the 9 markers corresponding to 8
      genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and
      347 controls from a Spanish population using KASPar probes. Genotypes were
      analyzed by logistic regression and adjusted by phenotypic characteristics.
      RESULTS: We confirm the protective role in MM of the rs3219090 located on the
      PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye
      color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4
      gene was associated with protection to develop MM for the dominant model (p-value
      0.037). We have also observed an association of this SNP with both lentigines (p
      value 0.014) and light eye color (p-value 3.76 * 10(-4)). Furthermore, we
      detected a novel association with rs1485993, located on the CCND1 gene, and dark
      eye color (p-value 4.96 * 10(-4)). Finally, rs1801516, located on the ATM gene,
      showed a trend towards a protective role in MM similar to the one firstly
      described in a GWAS study. CONCLUSIONS: To our knowledge, this is the first time
      that these SNPs have been associated with MM in a Spanish population. We
      confirmed the proposed role of rs3219090, located on the PARP1 gene, and
      rs12203592, located on the IRF4 gene, as protective to MM along the same lines as
      have previous genome-wide associated works. Finally, we have seen associations
      between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming
      previous results for the IRF4 gene and presenting novel data for the last two,
      suggesting that pigmentation characteristics correlated with eye color are
      potential mediators between PARP1 and MM protection.

PMID- 23537199
TI  - Characterising the biology of novel lytic bacteriophages infecting multidrug
      resistant Klebsiella pneumoniae.
AB  - BACKGROUND: Members of the genus Klebsiella are among the leading microbial
      pathogens associated with nosocomial infection. The increased incidence of
      antimicrobial resistance in these species has propelled the need for
      alternate/combination therapeutic regimens to aid clinical treatment.
      Bacteriophage therapy forms one of these alternate strategies. METHODS: Electron
      microscopy, burst size, host range, sensitivity of phage particles to
      temperature, chloroform, pH, and restriction digestion of phage DNA were used to
      characterize Klebsiella phages. RESULTS AND CONCLUSIONS: Of the 32 isolated
      phages eight belonged to the family Myoviridae, eight to the Siphoviridae whilst
      the remaining 16 belonged to the Podoviridae. The host range of these phages was
      characterised against 254 clinical Enterobacteriaceae strains including multidrug
      resistant Klebsiella isolates producing extended-spectrum beta-lactamases
      (ESBLs). Based on their lytic potential, six of the phages were further
      characterised for burst size, physicochemical properties and sensitivity to
      restriction endonuclease digestion. In addition, five were fully sequenced.
      Multiple phage-encoded host resistance mechanisms were identified. The
      Siphoviridae phage genomes (KP16 and KP36) contained low numbers of host
      restriction sites similar to the strategy found in T7-like phages (KP32). In
      addition, phage KP36 encoded its own DNA adenine methyltransferase. The phiKMV
      like KP34 phage was sensitive to all endonucleases used in this study. Dam
      methylation of KP34 DNA was detected although this was in the absence of an
      identifiable phage encoded methyltransferase. The Myoviridae phages KP15 and KP27
      both carried Dam and Dcm methyltransferase genes and other anti-restriction
      mechanisms elucidated in previous studies. No other anti-restriction mechanisms
      were found, e.g. atypical nucleotides (hmC or glucosyl hmC), although Myoviridae
      phage KP27 encodes an unknown anti-restriction mechanism that needs further
      investigation.

PMID- 23537200
TI  - Geochip-based analysis of microbial communities in alpine meadow soils in the
      Qinghai-Tibetan plateau.
AB  - BACKGROUND: GeoChip 3.0, a microbial functional gene array, containing ~28,000
      oligonucleotide probes and targeting ~57,000 sequences from 292 functional gene
      families, provided a powerful tool for researching microbial community structure
      in natural environments. The alpine meadow is a dominant plant community in the
      Qinghai-Tibetan plateau, hence it is important to profile the unique geographical
      flora and assess the response of the microbial communities to environmental
      variables. In this study, Geochip 3.0 was employed to understand the microbial
      functional gene diversity and structure, and metabolic potential and the major
      environmental factors in shaping microbial communities structure of alpine meadow
      soil in Qinghai-Tibetan Plateau. RESULTS: A total of 6143 microbial functional
      genes involved in carbon degradation, carbon fixation, methane oxidation and
      production, nitrogen cycling, phosphorus utilization, sulphur cycling, organic
      remediation, metal resistance, energy process and other category were detected in
      six soil samples and high diversity was observed. Interestingly, most of the
      detected genes associated with carbon degradation were derived from cultivated
      organisms. To identify major environmental factors in shaping microbial
      communities, Mantel test and CCA Statistical analyses were performed. The results
      indicated that altitude, C/N, pH and soil organic carbon were significantly (P <
      0.05) correlated with the microbial functional structure and a total of 80.97% of
      the variation was significantly explained by altitude, C/N and pH. The C/N
      contributed 38.2% to microbial functional gene variation, which is in accordance
      with the hierarchical clustering of overall microbial functional genes.
      CONCLUSIONS: High overall functional genes and phylogenetic diversity of the
      alpine meadow soil microbial communities existed in the Qinghai-Tibetan Plateau.
      Most of the genes involved in carbon degradation were derived from characterized
      microbial groups. Microbial composition and structures variation were
      significantly impacted by local environmental conditions, and soil C/N is the
      most important factor to impact the microbial structure in alpine meadow in
      Qinghai-Tibetan plateau.

PMID- 23537202
TI  - Resveratrol up-regulates the erythrocyte plasma membrane redox system and
      mitigates oxidation-induced alterations in erythrocytes during aging in humans.
AB  - Reactive oxygen/nitrogen species (ROS/RNS)-mediated oxidative damage followed by
      disturbed cellular homeostasis is involved in aging and related consequences.
      Lipid peroxidation, post-translational modifications of proteins, and an impaired
      defense system due to increased oxidative stress jeopardize cell fate and
      functions, resulting in cell senescence. Resveratrol, a natural stilbene, has
      extensively been reported to elicit a plethora of health-promoting effects. The
      present study carried out on 97 healthy human subjects (62 males and 35 females)
      of both sexes provides experimental evidence that resveratrol confers ability to
      up-regulate the plasma membrane redox system (PMRS) along with ascorbate free
      radical reductase, a compensatory system operating in the cell to maintain
      cellular redox state. Furthermore, resveratrol provided significant protection
      against lipid peroxidation and protein carbonylation and restored the cellular
      redox homeostasis measured in terms of glutathione (GSH) and sulfhydryl (-SH)
      group levels during oxidation injury in erythrocytes of different age groups in
      humans. Findings suggest a possible role of resveratrol in retardation of age
      dependent oxidative stress.

PMID- 23537203
TI  - Molecular mechanism of the inhibition of EGCG on the Alzheimer Abeta(1-42) dimer.
AB  - Growing evidence supports that amyloid beta (Abeta) oligomers are the major
      causative agents leading to neural cell death in Alzheimer's disease. The
      polyphenol (-)-epigallocatechin gallate (EGCG) was recently reported to inhibit
      Abeta fibrillization and redirect Abeta aggregation into unstructured, off
      pathway oligomers. Given the experimental challenge to characterize the
      structures of Abeta/EGCG complexes, we performed extensive atomistic replica
      exchange molecular dynamics simulations of Abeta1-42 dimer in the present and
      absence of EGCG in explicit solvent. Our equilibrium Abeta dimeric structures
      free of EGCG are consistent with the collision cross section from ion-mobility
      mass spectrometry and the secondary structure composition from circular dichroism
      experiment. In the presence of EGCG, the Abeta structures are characterized by
      increased inter-center-of-mass distances, reduced interchain and intrachain
      contacts, reduced beta-sheet content, and increased coil and alpha-helix
      contents. Analysis of the free energy surfaces reveals that the Abeta dimer with
      EGCG adopts new conformations, affecting therefore its propensity to adopt fibril
      prone states. Overall, this study provides, for the first time, insights on the
      equilibrium structures of Abeta1-42 dimer in explicit aqueous solution and an
      atomic picture of the EGCG-mediated conformational change on Abeta dimer.

PMID- 23537204
TI  - Objective structured assessment of technical competence in transthoracic
      echocardiography: a validity study in a standardised setting.
AB  - BACKGROUND: Competence in transthoracic echocardiography (TTE) is unrelated to
      traditional measures of TTE competence, such as duration of training and number
      of examinations performed. This study aims to explore aspects of validity of an
      instrument for structured assessment of echocardiographic technical skills.
      METHODS: The study included 45 physicians with three different clinical levels of
      echocardiography competence who all scanned the same healthy male following
      national guidelines. An expert in echocardiography (OG) evaluated all the
      recorded, de-identified TTE images blindly using the developed instrument for
      assessment of TTE technical skills. The instrument consisted of both a global
      rating scale and a procedure specific checklist. Two scores were calculated for
      each examination: A global rating score and a total checklist score. OG rated ten
      examinations twice for intra-rater reliability, and another expert rated the same
      ten examinations for inter-rater reliability. A small pilot study was then
      performed with focus on content validity. This pilot study included nine
      physicians who scanned three patients with different pathologies as well as
      different technical difficulties. RESULTS: Validity of the TTE technical skills
      assessment instrument was supported by a significant correlation found between
      level of expertise and both the global score (Spearman 0.76, p<0.0001) and the
      checklist score (Spearman 0.74, p<0.001). Both scores were able to distinguish
      between the three levels of competence that were represented in the physician
      group. Reliability was supported by acceptable inter- and intra-rater values. The
      pilot study showed a tendency to improved scores with increasing expertise
      levels, suggesting that the instrument could also be used when pathologies were
      present. CONCLUSIONS: We designed and developed a structured assessment
      instrument of echocardiographic technical skills that showed evidence of validity
      in terms of high correlations between test scores on a normal person and the
      level of physician competence, as well as acceptable inter- and intra-rater
      reliability scores. Further studies should, however, be performed to determine
      the adequate number of assessments needed to ensure high content validity and
      reliability in a clinical setting.

PMID- 23537205
TI  - Renal deterioration index: preoperative prognostic model for renal functional
      outcome after treatment of bilateral obstructive urolithiasis in patients with
      chronic kidney disease.
AB  - BACKGROUND AND PURPOSE: Patients who present with varying severity of obstructive
      urolithiasis behave differently after the treatment. Some patients recover with
      improved renal function while others progress to renal failure. Our objective was
      to objectively quantify which patients would progress to renal failure after
      treatment for obstructive urolithiasis. PATIENTS AND METHODS: A prospective
      analysis of 167 patients with renal failure from bilateral obstructive
      urolithiasis who were treated and subsequently followed for at least 1 year was
      performed. Failure was defined as glomerular filtration rate (GFR) values less
      than 15 mL/min at 1 year follow-up. All patients had preoperative placement of a
      percutaneous nephrostomy tube for at least 5 days before treatment with either
      ureteroscopy or percutaneous nephrolithotomy. Multiple logistic regression
      analysis of affecting parameters was performed. A renal deterioration index (RDI)
      was constructed based on scores assigned to varying severity of multivariate
      significant factors and the receiver operating characteristic (ROC) curve was
      analyzed. RESULTS: There were 48(28.7%) patients who progressed to CKD stage V at
      1-year follow-up. Combined cortical width (<= 0.001), proteinuria (0.01),
      positive urine culture (0.004), and nadir preoperative GFR postbilateral
      percutaneous nephrostomy (0.016) were statistically significant factors affecting
      renal deterioration on multivariate analysis. RDI has a high ROC curve (AUC=0.90)
      for predicting renal functional outcome. Combining these parameters in a
      prediction table yielded a RDI score >= 12 being associated with high odds risk
      (odds ratio=11.2) of treatment failure. CONCLUSION: RDI >= 12 is associated with
      renal deterioration after appropriate treatment of bilateral obstructive
      urolithiasis.

PMID- 23537206
TI  - Optimized gold nanoshell ensembles for biomedical applications.
AB  - : We theoretically study the properties of the optimal size distribution in the
      ensemble of hollow gold nanoshells (HGNs) that exhibits the best performance at
      in vivo biomedical applications. For the first time, to the best of our
      knowledge, we analyze the dependence of the optimal geometric means of the
      nanoshells' thicknesses and core radii on the excitation wavelength and the type
      of human tissue, while assuming lognormal fit to the size distribution in a real
      HGN ensemble. Regardless of the tissue type, short-wavelength, near-infrared
      lasers are found to be the most effective in both absorption- and scattering
      based applications. We derive approximate analytical expressions enabling one to
      readily estimate the parameters of optimal distribution for which an HGN ensemble
      exhibits the maximum efficiency of absorption or scattering inside a human tissue
      irradiated by a near-infrared laser.

PMID- 23537207
TI  - Design of a cyclotide antagonist of neuropilin-1 and -2 that potently inhibits
      endothelial cell migration.
AB  - Neuropilin-1 and -2 are critical regulators of angiogenesis, lymphangiogenesis,
      and cell survival as receptors for multiple growth factors. Disulfide-rich
      peptides that antagonize the growth factor receptors neuropilin-1 and neuropilin
      2 were developed using bacterial display libraries. Peptide ligands specific for
      the VEGFA binding site on neuropilin-1 were identified by screening a library of
      disulfide-rich peptides derived from the thermostable, protease-resistant
      cyclotide kalata B1. First generation ligands were subjected to one cycle of
      affinity maturation to yield acyclic peptides with affinities of 40-60 nM and
      slow dissociation rate constants (~1 * 10(-3) s(-1)). Peptides exhibited
      equivalent affinities for human and mouse neuropilin-1 and cross-reacted with
      human neuropilin-2 with lower affinity. A C-to-N cyclized variant (cyclotide) of
      one neuropilin ligand retained high affinity, exhibited increased protease
      resistance, and conferred improved potency for inhibiting endothelial cell
      migration in vitro (EC50 ~ 100 nM). These results demonstrate that potent, target
      specific cyclotides can be created by evolutionary design and that backbone
      cyclization can confer improved pharmacological properties. 

PMID- 23537208
TI  - Discovery-2: an interactive resource for the rational selection and comparison of
      putative drug target proteins in malaria.
AB  - BACKGROUND: Drug resistance to anti-malarial compounds remains a serious problem,
      with resistance to newer pharmaceuticals developing at an alarming rate. The
      development of new anti-malarials remains a priority, and the rational selection
      of putative targets is a key element of this process. Discovery-2 is an update of
      the original Discovery in silico resource for the rational selection of putative
      drug target proteins, enabling researchers to obtain information for a protein
      which may be useful for the selection of putative drug targets, and to perform
      advanced filtering of proteins encoded by the malaria genome based on a series of
      molecular properties. METHODS: An updated in silico resource has been developed
      where researchers are able to mine information on malaria proteins and predicted
      ligands, as well as perform comparisons to the human and mosquito host
      characteristics. Protein properties used include: domains, motifs, EC numbers, GO
      terms, orthologs, protein-protein interactions, protein-ligand interactions.
      Newly added features include drugability measures from ChEMBL, automated
      literature relations and links to clinical trial information. Searching by
      chemical structure is also available. RESULTS: The updated functionality of the
      Discovery-2 resource is presented, together with a detailed case study of the
      Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (PfSAHH) protein. A
      short example of a chemical search with pyrimethamine is also illustrated.
      CONCLUSION: The updated Discovery-2 resource allows researchers to obtain
      detailed properties of proteins from the malaria genome, which may be of interest
      in the target selection process, and to perform advanced filtering and selection
      of proteins based on a relevant range of molecular characteristics.

PMID- 23537209
TI  - Are non-attenders a concern for primary care practice?
AB  - The article by Eshel et al. describes major differences, in terms of demography
      and health status, between elderly patients who did and those who did not visit
      primary care physicians for general health check-ups. The authors conclude that
      non-attenders are not at risk for developing health conditions.While this study
      by Eshel et al. provides a better understanding of the primary care population,
      the conclusion (no need for reaching out to the non-attenders) should be viewed
      with caution. In this study, non-attenders 'have a higher probability of being
      women, older, not married and from a lower socio-economic' segment of the
      population, a population that is known to be at higher risk for chronic disease.
      In addition, outreach programs in primary care would be key in providing
      essential preventive measures for this vulnerable population (e.g., osteoporosis
      prevention, vaccination, lifestyle, etc.).This is a commentary on
      http://www.ijhpr.org/content/2/1/7.

PMID- 23537210
TI  - Late presenters among persons with a new HIV diagnosis in Italy, 2010-2011.
AB  - BACKGROUND: In Western Europe, about 50% of newly diagnosed HIV-positive
      individuals are diagnosed at a late stage disease and enter in care late (i.e.
      with a CD4 count <=350 MUL/MUL). The aim of the present study is to analyze the
      characteristics and the factors associated with being diagnosed late or at an
      advanced stage of disease among persons with a new HIV diagnosis in Italy, in the
      period 2010-2011. METHODS: We used individual data on new HIV diagnoses reported
      by the HIV surveillance system in 2010 and in 2011. Persons with CD4 <=350
      cells/MUL or diagnosed with AIDS (regardless of the CD4 cell count) were defined
      as late presenters (LP); persons with CD4 <= 200 cells/MUL or AIDS (regardless of
      the CD4 cell count) were defined as presenting with advanced HIV disease (AHD).
      RESULTS: Of the 7,300 new diagnoses reported in 2010-2011 by the included
      regions, 55.2% were LP; among these, 37.9% was diagnosed with AIDS. Persons
      presenting with AHD were 37.8%. The median age of LP was 40 years (IQR 33-48),
      significantly higher (p < 0.001) than that of non-LP (35 years); 73.9% were
      males; 30.7% were non-nationals. The median age of AHD was 42 years (IQR 35-50),
      74.5% were males; 31.1% were non-nationals. The proportion of LP among IDUs was
      59.8%, among heterosexuals (HET) 61.1% and among MSM 44.3%. The proportion of AHD
      among IDUs was 43.6%, among HET 43.2% and among MSM 27.4%. Factors significantly
      associated with being LP were: age older than 50 years (OR = 4.6 [95% CI 3.8
      5.6]); having been diagnosed in Southern Italy (Southern vs Northern Italy OR =
      1.5 [95% CI 1.3-1.7]) having been diagnosed in Central Italy (Central vs Northern
      Italy OR = 1.3 [95% CI 1.1-1.6]); being HET (HET vs MSM, OR = 1.7 [95% CI 1.5
      2.0]), being non-national (Non-national vs Italian, OR 1.7 (95% CI 1.5-2.0);
      being IDU (IDU vs MSM, OR = 1.6 [95% CI 1.2-2.1]). The same factors were
      significantly associated with being AHD. CONCLUSIONS: Older people, people
      diagnosed in Central and Southern Italy, non nationals, and persons who acquired
      the infection through injecting drug use or heterosexual contact showed a higher
      risk of being diagnosed late. A more active offer of HIV testing and targeted
      interventions focussed on these populations are needed to optimize early access
      to care and treatment.

PMID- 23537211
TI  - "V-PLASTY": a novel technique to reconstruct pulmonary valvular and annular
      stenosis in patients with right ventricular outflow tract obstruction.
AB  - BACKGROUND: The goal of repair of right ventricular outflow tract obstruction
      with or without Tetralogy of Fallot (TOF) is to eliminate valvular and/or
      subvalvular obstruction. However, this operation has a high risk of late
      complication of pulmonary insufficiency. In this study, we aimed to present early
      period results of our new technique that we call "V-Plasty" developed to prevent
      pulmonary insufficiency after pulmonary valve reconstruction in selected
      patients. METHODS: Between January 2006 and January 2010, we performed V-plasty
      for pulmonary valve reconstruction in 10 patients. Eight patients (5 males, 3
      females) had TOF and 2 patients (1 male, 1 female) had atrial septal defect
      concomitant with pulmonary valve stenosis. Patient selection for V-plasty
      reconstruction was made due to the pulmonary valve anatomy and degree of
      stenosis. The mean follow-up time was 55.7 +/- 16.2 months (ranging from 32 to 80
      months). RESULTS: Functional capacity of the patients improved immediately after
      the surgery. There were no mortality and re-operation in follow-up period.
      Patients were followed up with echocardiography one week after the operation, at
      1st, 6th, 12th months and annually. There was no pulmonary insufficiency.
      CONCLUSIONS: Operative correction of the pulmonary outflow tract obstruction with
      or without TOF, frequently requires transannular enlargement because of the
      infundibular and/or annular-valvular obstruction. This conventional technique is
      usually a reason for late pulmonary insufficiency. In our study, we have not seen
      pulmonary insufficiency in early term follow-up period. Our early term results
      are encouraging, but long term follow-up results are needed with large case
      series.

PMID- 23537213
TI  - Is intermittent hypoxia a cause of aging?
AB  - Insufficient tissue oxygenation occurs in a wide range of physiological and
      pathological conditions. Reactive oxygen species (ROS) are physiological products
      of aerobic life and their accumulation affects aging. Chronic intermittent
      hypoxia can lead to oxidative stress that could predispose the organism to
      cumulative acceleration of the aging process.

PMID- 23537212
TI  - Genome-wide associations of signaling pathways in glioblastoma multiforme.
AB  - BACKGROUND: eQTL analysis is a powerful method that allows the identification of
      causal genomic alterations, providing an explanation of expression changes of
      single genes. However, genes mediate their biological roles in groups rather than
      in isolation, prompting us to extend the concept of eQTLs to whole gene pathways.
      METHODS: We combined matched genomic alteration and gene expression data of
      glioblastoma patients and determined associations between the expression of
      signaling pathways and genomic copy number alterations with a non-linear machine
      learning approach. RESULTS: Expectedly, over-expressed pathways were largely
      associated to tag-loci on chromosomes with signature alterations. Surprisingly,
      tag-loci that were associated to under-expressed pathways were largely placed on
      other chromosomes, an observation that held for composite effects between
      chromosomes as well. Indicating their biological relevance, identified genomic
      regions were highly enriched with genes having a reported driving role in
      gliomas. Furthermore, we found pathways that were significantly enriched with
      such driver genes. CONCLUSIONS: Driver genes and their associated pathways may
      represent a functional core that drive the tumor emergence and govern the
      signaling apparatus in GBMs. In addition, such associations may be indicative of
      drug combinations for the treatment of brain tumors that follow similar patterns
      of common and diverging alterations.

PMID- 23537214
TI  - Personal DNA testing in college classrooms: perspectives of students and
      professors.
AB  - Discourse on the integration of personal genetics and genomics into classrooms is
      increasing; however, limited data have been collected on the perspectives of
      students and professors. We conducted a cross-sectional survey of undergraduate
      and graduate students as well as professors at two major universities to assess
      attitudes regarding the use of personal DNA testing and other personalized
      activities in college classrooms. Students indicated that they were more likely
      to enroll (60.2%) in a genetics course if it offered personal DNA testing;
      undergraduate students were more likely than graduate students to enroll if
      personal DNA testing was offered (p=0.029). Students who majored in the physical
      sciences were less likely to enroll than students in the biological or social
      sciences (p=0.019). Students also indicated that when course material is
      personalized, the course is more interesting (94.6%) and the material is easier
      to learn (87.3%). Professors agreed that adding a personalized element increases
      student interest, participation, and learning (86.0%, 82.6%, and 72.6%,
      respectively). The results of this study indicate that, overall, students and
      professors had a favorable view of the integration of personalized information,
      including personal DNA testing, into classroom activities, and students welcomed
      more opportunities to participate in personalized activities.

PMID- 23537215
TI  - The association between heterozygosity for UGT1A1*6, UGT1A1*28, and variation in
      the serum total-bilirubin level in healthy young Japanese adults.
AB  - AIMS: Considerable variations in the serum total-bilirubin concentrations are
      observed in healthy subjects. Both sex and the UGT1A1 homozygous genotypes,*6/*6
      and *28/*28, are known to influence this variation. However, currently, there is
      no consensus on the relationship of the heterozygous genotypes *1/*6, *1/*28, or
      *6/*28 and interindividual variation in the serum total-bilirubin levels. In the
      present study, we sought to clarify the involvement of heterozygous alleles *6
      and *28 in the interindividual difference in the serum total-bilirubin levels
      among healthy young Japanese adults. METHODS: We enrolled 92 healthy Japanese
      aged 20-30 years (37 men and 55 women). The serum total-bilirubin levels were
      compared between men and women and with different UGT1A1 genotypes. Multiple
      regression analysis was used to investigate the relationships between individual
      differences in the serum total-bilirubin levels, UGT1A1 genetic variants, and
      sex. RESULTS: Serum total-bilirubin levels were significantly lower in women than
      in men. There were also significant differences in the serum total-bilirubin
      levels between the *1/*1 and *1/*28 genotype, the *1/*1 and *6/*28 genotype, the
      *1/*6 and *1/*28 genotype, and also the *1/*6 and *6/*28 genotype. Multiple
      regression analysis showed significant relationships between the serum total
      bilirubin level, the UGT1A1 genotypes *1/*28 and *6/*28, and sex. This model
      explained 42.3% of the interindividual variation in serum total-bilirubin levels.
      CONCLUSIONS: We found that the UGT1A1 genotypes *1/*28 and *6/*28 as well as sex
      contributed to interindividual variations in the serum total-bilirubin levels. In
      contrast, UGT1A1*1/*6 showed only minimal involvement in individual differences
      in serum total-bilirubin levels.

PMID- 23537216
TI  - Validation of standards for quantitative assessment of JAK2 c.1849G>T (p.V617F)
      allele burden analysis in clinical samples.
AB  - The substitution of valine with phenylalanine at amino acid 617 of the Janus
      kinase 2 (JAK2) gene (JAK2 p.V617F) occurs in a high proportion of patients with
      myeloproliferative neoplasms (MPNs). The ability to accurately measure JAK2
      p.V617F allele burden is of great interest given the diagnostic relevance of the
      mutation and the ongoing clinical evaluation of JAK inhibitors. A main hurdle in
      developing quantitative assays for allele burden measurement is the
      unavailability of accurate standards for both assay validation and use in a
      standard curve for quantification. We describe our approach to the validation of
      standards for quantitative assessment of JAK2 p.V617F allele burden in clinical
      MPN samples. These standards were used in two JAK2 p.V617F assays, which were
      used to support clinical studies of ruxolitinib (Jakafi((r))) in myelofibrosis, a
      real-time polymerase chain reaction assay for initial screening of all samples,
      and a novel single-nucleotide polymorphism typing (SNaPshot)-based assay for
      samples with less than 5% mutant allele burden. Comparisons of allele burden data
      from clinical samples generated with these assays show a high degree of
      concordance with each other and with a pyrosequencing-based assay used for
      clinical reporting from an independent laboratory, thus providing independent
      validation to the accuracy of these standards.

PMID- 23537217
TI  - A novel panel of biomarkers in distinction of small well-differentiated HCC from
      dysplastic nodules and outcome values.
AB  - BACKGROUND: Differential diagnosis of high-grade dysplastic nodules (HGDN) and
      well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to
      experienced hepatic clinicians, radiologists and hepatopathologists. METHODS: The
      expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and
      glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were
      assessed by immunohistochemistry. The differential diagnostic performances of
      these three markers alone and in combination for HGDN and WDHCC were investigated
      by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an
      independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival
      and time to recurrence were evaluated by univariate and multivariate analyses in
      an independent set of 500 patients. RESULTS: ACY1, SQSTM1 and GPC3 were
      differentially expressed in each group. For the differential diagnosis of WDHCC
      from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 +
      GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set,
      which were higher than any of the three two-marker combinations. The validities
      of the four diagnostic models were further confirmed in an independent test set,
      and corresponding good sensitivity and specificity were observed. Interestingly,
      GPC3 expression in HCC tissues combined with serum alpha-fetoprotein (AFP) was
      found to be an independent predictor for overall survival and time to recurrence.
      CONCLUSIONS: ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable
      biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry.
      Meanwhile, low GPC3 staining combined with positive serum AFP may play a
      practical role in predicting poor postoperative outcome and high tumor recurrence
      risk.

PMID- 23537218
TI  - Reproduction of hemangioma by infection with subgroup J avian leukosis virus: the
      vertical transmission is more hazardous than the horizontal way.
AB  - BACKGROUND: Clinical cases of hemangioma associated with subgroup J avian
      leukosis virus (ALV-J) have been reported in commercial chicken layer flocks
      since 2006. We attempted to reproduce hemangioma through experimental infection
      with ALV-J to evaluate viral pathogenicity in layer birds and their progenies.
      RESULTS: Body weight and indexes for immune organs of chickens infected with ALV
      J strain SCDY1 were lower than those in controls. Proliferation of lymphocytes
      was observed in many tissues, and viral integration was detected in the genome of
      lymphocytes at 14 days post-infection, along with virus shedding. ALV-J was also
      efficiently transmitted from eggs to progenies. Embryo hatchability and progeny
      mortality were lower than those for controls. The efficiencies of virus shedding
      and virus integration in the lymphocytes of progenies were higher than those in
      parents. CONCLUSIONS: ALV-J is able to inhibit the growth of infected chickens,
      and causes damage to immune organs. Vertical transmission of ALV-J appears to be
      more deleterious than horizontal transmission.

PMID- 23537220
TI  - Activation of dimanganese class Ib ribonucleotide reductase by hydrogen peroxide:
      mechanistic insights from density functional theory.
AB  - Activation of manganese-dependent class Ib ribonucleotide reductase by hydrogen
      peroxide was modeled using B3LYP* hybrid density functional theory. Class Ib
      ribonucleotide reductase R2 subunit (R2F) does not react with molecular oxygen.
      Instead R2F is proposed to react with H2O2 or HO2(-), provided by the unusual
      flavodoxin protein NrdI, to generate the observed manganese(III) manganese(III)
      tyrosyl-radical state. On the basis of the calculations, an energetically
      feasible reaction mechanism is suggested for activation by H2O2, which proceeds
      through two reductive half-reactions. In the first reductive half-reaction, H2O2
      is cleaved with a barrier of 13.1 kcal mol(-1) [Mn(II)Mn(II) -> Mn(III)Mn(III)],
      and in the second reductive half-reaction, H2O2 is cleaved with a barrier of 17.0
      kcal mol(-1) [Mn(III)Mn(III) -> Mn(IV)Mn(IV)]. Tyrosyl-radical formation from
      both the Mn(IV)Mn(IV) state and a Mn(III)Mn(IV) state, where an electron and
      proton have been taken up, is both kinetically and thermodynamically accessible.
      Hence, chemically, H2O2 is a possible oxidant for the manganese-dependent R2F.
      The selectivity between the second reductive half-reaction and a competing
      oxidative reaction, as in manganese catalase, may be the time scale for the
      availability of H2O2. The role of NrdI may be to provide H2O2 on the correct time
      scale.

PMID- 23537221
TI  - Flexible cystoscopy and Holmium:Yttrium aluminum garnet laser ablation for
      recurrent nonmuscle invasive bladder carcinoma under local anesthesia.
AB  - PURPOSE: The management of recurrent nonmuscle invasive bladder cancer (NMIBC)
      post-transurethral resection has been based around electrocautery techniques,
      either under local or general anesthetic. We determine the long-term outcome of
      the management of NMIBC recurrences treated with Holmium:Yttrium Aluminum Garnet
      (Ho:YAG) laser ablation under local anesthetic with a flexible cystoscope.
      PATIENTS AND METHODS: We performed a prospective analysis of 151 consecutive
      patients, undergoing treatment of 444 tumors, between 2006 and 2011 in a
      University Teaching Hospital. Median follow-up was 24 months (0-58 months). The
      primary outcome was local, on-site recurrence rates of NMIBC. The secondary
      outcome measure included off-site recurrence rates, complications, pain
      perception, and patient satisfaction. RESULTS: Local, on-site recurrence rates
      after first treatment for all NMIBC disease were 10%. In patients with low risk
      NMIBC (G1/2, Ta), this reduced to around 4% post laser treatment. Higher
      recurrence rates (14%) were seen in those with high-grade (G3, T1) disease.
      Treatment was more successful with disease around the trigone, posterior and
      lateral bladder walls, with a significantly higher risk of recurrence for tumor
      around the ureteric orifice. The median time to local recurrence was 12 months
      and off-site recurrence was 25 months. Complication rates were low: dysuria
      (4.2%), frequency (1.5%), and hematuria (1.9%), with no episodes of bladder
      perforation. Visual analog pain scores were low, mean score 1 (range 0-7). The
      overall patient satisfaction was 100%. CONCLUSIONS: Flexible cystoscopy and
      Ho:YAG laser therapy should be considered as a first line treatment option for
      the management of recurrence in low-grade NMIBC (G1/2, Ta/1) throughout the
      bladder, except around the ureteric orifices. For those with high-grade disease
      (G3), the recurrences rates are increased, but the procedure still offers an
      acceptable recurrence rate. It provides good local disease control, low
      complications, patient acceptability and tolerance.

PMID- 23537222
TI  - Relationship between the population incidence of pertussis in children in New
      South Wales, Australia and emergency department visits with cough: a time series
      analysis.
AB  - BACKGROUND: Little is known about the potential of syndromic surveillance to
      provide early warning of pertussis outbreaks. We conducted a time series analysis
      to assess whether an emergency department (ED) cough syndrome would respond to
      changes in the incidence of pertussis in children aged under 10 years in New
      South Wales (NSW), Australia, and to evaluate the timing of any association. A
      further aim was to assess the lag between the onset of pertussis symptoms and
      case notification in the infectious diseases surveillance system in NSW. METHODS:
      Using routinely collected data, we prepared a daily count time series of visits
      to NSW EDs assigned a provisional diagnosis of cough. Separate daily series were
      prepared for three independent variables: notifications of cases of pertussis and
      influenza and ED visits with bronchiolitis (a proxy measure of respiratory
      syncytial virus (RSV) infection). The study period was 1/1/2007-31/12/2010. A
      negative binomial multivariate model was used to assess associations between the
      outcome and independent variables. We also evaluated the median delay in days
      between the estimated onset of a case of pertussis and the date the local public
      health authority was notified of that case. RESULTS: When notified pertussis
      increased by 10 cases in one day, ED visits with cough increased by 5.2% (95%
      confidence interval (CI): 0.5%-10.0%) seven days later. Daily increases in the
      other independent variables had a smaller impact on cough visits. When notified
      influenza increased by 10 cases in one day, ED visits with cough increased by
      0.8% (95% CI: 0%-1.7%) seven days later. When ED visits with bronchiolitis
      increased by 10 visits in one day, ED visits with cough increased by 4.8% (95%
      CI: 1.2%-8.6%) one day earlier. The median interval between estimated onset of
      pertussis and case notification was seven days. CONCLUSIONS: Pertussis appears to
      be an important driver of ED visits with cough in children aged under 10 years.
      However, the median delay in notification of cases of pertussis was similar to
      the lag in the pertussis-associated short-term increases in ED visits with cough.
      Elevations in RSV and influenza activity may also explain increases in the ED
      cough syndrome. Real time monitoring of ED visits with cough in children is
      therefore unlikely to consistently detect a potential outbreak of pertussis
      before passive surveillance.

PMID- 23537223
TI  - A strongly absorbing class of non-natural labels for probing protein
      electrostatics and solvation with FTIR and 2D IR spectroscopies.
AB  - A series of non-natural infrared probes is reported that consist of a metal
      tricarbonyl modified with a -(CH2)n- linker and cysteine-specific leaving group.
      They can be site-specifically attached to proteins using mutagenesis and similar
      protocols for EPR spin labels, which have the same leaving group. We characterize
      the label's frequencies and lifetimes using 2D IR spectroscopy in solvents of
      varying dielectric. The frequency range spans 10 cm(-1), and the variation in
      lifetimes ranges from 6 to 19 ps, indicating that these probes are very sensitive
      to their environments. Also, we attached probes with -(CH2)-, -(CH2)3-, and 
      (CH2)4- linkers to ubiquitin at positions 6 and 63 and collected spectra in
      aqueous buffer. The frequencies and lifetimes were correlated for 3C and 4C
      linkers, as they were in the solvents, but did not correlate for the 1C linker.
      We conclude that lifetime measures solvation, whereas frequency reflects the
      electrostatics of the environment, which in the case of the 1C linker is a
      measure of the protein electrostatic field. We also labeled V71C alpha-synuclein
      in buffer and membrane-bound. Unlike most other infrared labels, this label has
      extremely strong cross sections and thus can be measured with 2D IR spectroscopy
      at sub-millimolar concentrations. We expect that these labels will find use in
      studying the structure and dynamics of membrane-bound, aggregated, and
      kinetically evolving proteins for which high signal-to-noise at low protein
      concentrations is imperative.

PMID- 23537224
TI  - Biopsy findings in giant cell arteritis: relationship to baseline factors and
      corticosteroid treatment.

PMID- 23537225
TI  - The effect of peanut and grain bar preloads on postmeal satiety, glycemia, and
      weight loss in healthy individuals: an acute and a chronic randomized
      intervention trial.
AB  - BACKGROUND: Peanut consumption favorably influences satiety. This study examined
      the acute effect of peanut versus grain bar preloads on postmeal satiety and
      glycemia in healthy adults and the long-term effect of these meal preloads on
      body mass in healthy overweight adults. METHODS: In the acute crossover trial (n
      = 15; 28.4 +/- 2.9 y; 23.1 +/- 0.9 kg/m2), the preload (isoenergetic peanut or
      grain bar with water, or water alone) was followed after 60 min with ingestion of
      a standardized glycemic test meal. Satiety and blood glucose were assessed
      immediately prior to the preload and to the test meal, and for two hours postmeal
      at 30-min intervals. In the parallel-arm, randomized trial (n = 44; 40.5 +/- 1.6
      y, 31.8 +/- 0.9 kg/m2), the peanut or grain bar preload was consumed one hour
      prior to the evening meal for eight weeks. Body mass was measured at 2-week
      intervals, and secondary endpoints included blood hemoglobin A1c and energy
      intake as assessed by 3-d diet records collected at pre-trial and trial weeks 1
      and 8. RESULTS: Satiety was elevated in the postprandial period following grain
      bar ingestion in comparison to peanut or water ingestion (p = 0.001, repeated
      measures ANOVA). Blood glucose was elevated one hour after ingestion of the grain
      bar as compared to the peanut or water treatments; yet, total glycemia did not
      vary between treatments in the two hour postprandial period. In the 8-week trial,
      body mass was reduced for the grain bar versus peanut groups after eight weeks (
      1.3 +/- 0.4 kg versus -0.2 +/- 0.3 kg, p = 0.033, analysis of covariance). Energy
      intake was reduced by 458 kcal/d in the first week of the trial for the grain bar
      group as compared to the peanut group (p = 0.118). Hemoglobin A1c changed
      significantly between groups during the trial (-0.25 +/- 0.07% and -0.18 +/-
      0.12% for the grain bar and peanut groups respectively, p = 0.001). CONCLUSIONS:
      Compared to an isoenergetic peanut preload, consumption of a grain bar preload
      one hour prior to a standardized meal significantly raised postmeal satiety.
      Moreover, consumption of the grain bar prior to the evening meal was associated
      with significant weight loss over time suggesting that glycemic carbohydrate
      ingestion prior to meals may be a weight management strategy.

PMID- 23537226
TI  - Design of a multi-walled carbon nanotube field emitter with micro vacuum gauge.
AB  - The variation of vacuum level inside a field emission device when electron is
      emitted from multi-walled carbon nanotubes (MWCNTs) by electric field was
      measured where MWCNT gauge packaged with a vacuum device was used to measure the
      degree of a vacuum until the end of the vacuum device life. It was found that the
      electrical properties of MWCNTs altered with the degree of a vacuum. We
      fabricated MWCNT gauge which were printed and pasted by the screen printer. In
      this paper, we report the successful detection of the ionization of gases in
      vacuum state.

PMID- 23537227
TI  - NMR crystallography of enzyme active sites: probing chemically detailed, three
      dimensional structure in tryptophan synthase.
AB  - NMR crystallography--the synergistic combination of X-ray diffraction, solid
      state NMR spectroscopy, and computational chemistry--offers unprecedented insight
      into three-dimensional, chemically detailed structure. Initially, researchers
      used NMR crystallography to refine diffraction data from organic and inorganic
      solids. Now we are applying this technique to explore active sites in
      biomolecules, where it reveals chemically rich detail concerning the interactions
      between enzyme site residues and the reacting substrate. Researchers cannot
      achieve this level of detail from X-ray, NMR,or computational methodologies in
      isolation. For example, typical X-ray crystal structures (1.5-2.5 A resolution)
      of enzyme-bound intermediates identify possible hydrogen-bonding interactions
      between site residues and substrate but do not directly identify the protonation
      states. Solid-state NMR can provide chemical shifts for selected atoms of enzyme
      substrate complexes, but without a larger structural framework in which to
      interpret them only empirical correlations with local chemical structure are
      possible. Ab initio calculations and molecular mechanics can build models for
      enzymatic processes, but they rely on researcher-specified chemical details.
      Together, however, X-ray diffraction, solid-state NMR spectroscopy, and
      computational chemistry can provide consistent and testable models for structure
      and function of enzyme active sites: X-ray crystallography provides a coarse
      framework upon which scientists can develop models of the active site using
      computational chemistry; they can then distinguish these models by comparing
      calculated NMR chemical shifts with the results of solid-state NMR spectroscopy
      experiments. Conceptually, each technique is a puzzle piece offering a generous
      view of the big picture. Only when correctly pieced together, however, can they
      reveal the big picture at the highest possible resolution. In this Account, we
      detail our first steps in the development of NMR crystallography applied to
      enzyme catalysis. We begin with a brief introduction to NMR crystallography and
      then define the process that we have employed to probe the active site in the
      beta-subunit of tryptophan synthase with unprecedented atomic-level resolution.
      This approach has resulted in a novel structural hypothesis for the protonation
      state of the quinonoid intermediate in tryptophan synthase and its surprising
      role in directing the next step in the catalysis of L-Trp formation.

PMID- 23537229
TI  - Solution-processed, antimony-doped tin oxide colloid films enable high
      performance TiO2 photoanodes for water splitting.
AB  - Photoelectrochemical (PEC) water splitting and solar fuels hold great promise for
      harvesting solar energy. TiO2-based photoelectrodes for water splitting have been
      intensively investigated since 1972. However, solar-to-fuel conversion
      efficiencies of TiO2 photoelectrodes are still far lower than theoretical values.
      This is partially due to the dilemma of a short minority carrier diffusion
      length, and long optical penetration depth, as well as inefficient electron
      collection. We report here the synthesis of TiO2 PEC electrodes by coating
      solution-processed antimony-doped tin oxide nanoparticle films (nanoATO) on FTO
      glass with TiO2 through atomic layer deposition. The conductive, porous nanoATO
      film-supported TiO2 electrodes, yielded a highest photocurrent density of 0.58
      mA/cm(2) under AM 1.5G simulated sunlight of 100 mW/cm(2). This is approximately
      3* the maximum photocurrent density of planar TiO2 PEC electrodes on FTO glass.
      The enhancement is ascribed to the conductive interconnected porous nanoATO film,
      which decouples the dimensions for light absorption and charge carrier diffusion
      while maintaining efficient electron collection. Transient photocurrent
      measurements showed that nanoATO films reduce charge recombination by
      accelerating transport of photoelectrons through the less defined conductive
      porous nanoATO network. Owing to the large band gap, scalable solution processed
      porous nanoATO films are promising as a framework to replace other conductive
      scaffolds for PEC electrodes.

PMID- 23537230
TI  - Use of spirometry in the diagnosis of COPD: a qualitative study in primary care.
AB  - Guidelines that recommend spirometry to confirm airflow obstruction among
      patients with suspected COPD are not routinely followed. We conducted a
      qualitative study to identify attitudes and barriers of primary care physicians
      to performing spirometry for patients with possible COPD. We conducted four focus
      groups, each with three primary care physicians (PCPs) who practice in an urban,
      academic medical center. In general, PCPs believed that spirometry was not
      necessary to confirm the diagnosis of COPD. Compared to other co-morbid
      conditions, in a patient with a diagnosis of COPD without self-reported symptoms,
      COPD was not a priority during a clinic visit. This was in part due to the belief
      that there was lack of evidence that medication used in COPD lead to improved
      outcomes and that there was no point of care measure for COPD compared to other
      co-morbid conditions such as diabetes mellitus or hypertension. Health system
      barriers specific to spirometry use was not identified. In conclusion, in our
      sample of PCPs, there was skepticism that spirometry is warranted to diagnose and
      manage COPD. Availability of spirometry was not a perceived barrier. Our results
      explain, in part, why previous interventions to improve access to spirometry and
      diagnosis of COPD in primary care settings have been difficult to conduct and/or
      have had marginal success. Our findings strongly suggest that a first step toward
      increasing the use of spirometry among primary care physicians is to have them
      believe in its utility in the diagnosis of COPD.

PMID- 23537232
TI  - Have we made progress in Somalia after 30 years of interventions? Attitudes
      toward female circumcision among people in the Hargeisa district.
AB  - BACKGROUND: Female circumcision is a major public health problem that largely
      contributes to the ill-health of women and their children globally. Accordingly,
      the international community is committed to take all possible measures to abolish
      the practice that is internationally considered to be absolutely intolerable.
      While the practice is a social tradition shared by people in 28 African
      countries, there is no country on earth where FC is more prevalent than in
      Somalia. Yet, since the early 1990s, there is no quantitative study that has
      investigated whether the perception towards the practice among Somali men and
      women in Somalia has improved or not. Thus, this cross-sectional quantitative
      study examines the attitudes toward the practice among people in Hargeisa,
      Somalia. METHODS: A cross-sectional study of 215 randomly selected persons,
      including both men and women, was conducted in Hargeisa, Somalia from July to
      September of 2011. Participants were interviewed using structured questionnaires,
      with questions including the circumcision status of the female participants, the
      type of circumcision, if one has the intention to circumcise his/her daughter,
      whether one supports the continuation or discontinuation of the practice and
      men's perceptions toward having an uncircumcised woman as a wife. RESULT: The
      findings show that 97% of the study's participants were circumcised with no age
      differences. Of this, 81% were subjected to Type 3, while 16% were subjected to
      either Type 1 or 2 and only 3% were left uncircumcised. Approximately 85% of the
      respondents had intention to circumcise their daughters, with 13% were planning
      the most radical form. Among men, 96% preferred to marry circumcised women,
      whereas overall, 90% of respondents supported the continuation of the practice.
      The vast majority of the study's respondents had a good knowledge of the negative
      health effects of female circumcision. In multivariate logistic regressions, with
      an adjustment for all other important variables, female circumcision (the Sunna
      form) is a religious requirement 16.5 (2.43-112.6) and the Sunna form is not
      harmful 25.1(2.35-281.1), are the two factors significantly associated with the
      continuation of female circumcision. Moreover, females were less likely to
      support the continuation of FC compared to their male counterparts (aOR 0.07; CI:
      0.05-0.88). CONCLUSION: The study shows that the support towards the persistence
      of the practice is profoundly high in Somalia. People are aware of the health and
      human rights effect of female circumcision, and yet they support the continuation
      of the practice. Therefore, over 30 years of campaigns with limited progress
      demand an alternative approach towards the eradication of female circumcision in
      Somalia.

PMID- 23537231
TI  - Randomized controlled trial to evaluate the effects of progressive resistance
      training compared to progressive muscle relaxation in breast cancer patients
      undergoing adjuvant radiotherapy: the BEST study.
AB  - BACKGROUND: Cancer-related fatigue (CRF) is one of the most common and
      distressing side effects of cancer and its treatment. During and after
      radiotherapy breast cancer patients often suffer from CRF which frequently
      impairs quality of life (QoL). Despite the high prevalence of CRF in breast
      cancer patients and the severe impact on the physical and emotional well-being,
      effective treatment methods are scarce.Physical activity for breast cancer
      patients has been reported to decrease fatigue, to improve emotional well-being
      and to increase physical strength. The pathophysiological and molecular
      mechanisms of CRF and the molecular-biologic changes induced by exercise,
      however, are poorly understood.In the BEST trial we aim to assess the effects of
      resistance training on fatigue, QoL and physical fitness as well as on molecular,
      immunological and inflammatory changes in breast cancer patients during adjuvant
      radiotherapy. METHODS/DESIGN: The BEST study is a prospective randomized,
      controlled intervention trial investigating the effects of a 12-week supervised
      progressive resistance training compared to a 12-week supervised muscle
      relaxation training in 160 patients with breast cancer undergoing adjuvant
      radiotherapy. To determine the effect of exercise itself beyond potential
      psychosocial group effects, patients in the control group perform a group-based
      progressive muscle relaxation training. Main inclusion criterion is
      histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy
      with indication for adjuvant radiotherapy. Main exclusion criteria are acute
      infectious diseases, severe neurological, musculosceletal or cardiorespiratory
      disorders. The primary endpoint is cancer-related fatigue; secondary endpoints
      include immunological and inflammatory parameters analyzed in peripheral blood,
      saliva and urine. In addition, QoL, depression, physical performance and
      cognitive capacity will be assessed. DISCUSSION: The BEST study is the first
      randomized controlled trial comparing progressive resistance training with muscle
      relaxation training in breast cancer patients during adjuvant radiotherapy. Based
      on the analysis of physiological, immunological and inflammatory parameters it
      will contribute to a better understanding of the physiological and psychosocial
      effects and the biological mechanisms of resistance training. The ultimate goal
      is the implementation of optimized intervention programs to reduce fatigue,
      improve quality of life and potentially the prognosis after breast cancer. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01468766.

PMID- 23537233
TI  - Recent advances in the understanding of teleost medaka ovulation: the roles of
      proteases and prostaglandins.
AB  - Ovulation is the process of liberating oocytes from the preovulatory follicles,
      and is observed in the ovaries of virtually all female vertebrate animals.
      Compared with mammalian species, there have been far fewer studies that address
      the ovulatory mechanisms of non-mammalian species. We have examined the molecular
      mechanism of follicle rupture during ovulation using the teleost model, medaka,
      or Oryzias latipes. Follicle rupture in medaka ovulation involves the cooperation
      of the tissue inhibitor of metalloproteinase-2b protein with at least three
      matrix metalloproteinases (MMP): membrane type-1 MMP (MT1-MMP), MT2-MMP, and
      gelatinase A. Our studies also indicate that the serine protease, i.e., plasmin,
      participates in the rupture for only a few hours prior to the activation of MMP
      mediated hydrolysis at ovulation. The involvement of prostaglandin E2 (PGE2) in
      medaka ovulation was also demonstrated. Cyclooxygenase-2 and PGE2 receptor
      subtype EP4b were respectively shown to be an enzyme responsible for PGE2
      synthesis and a receptor for the generated ligand in the preovulatory follicles.
      Based on the results obtained from our studies of fish, we discuss the
      similarities and differences in vertebrate ovulation compared with mammalian
      species.

PMID- 23537234
TI  - The role of scent-marking in patchy and highly fragmented populations of the
      Cabrera vole (Microtus cabrerae Thomas, 1906).
AB  - Rodent scent-marking is often used for territorial defence and self
      advertisement, and both functions often entail the continuous scent-marking of a
      large area with high costs. In species with highly-fragmented populations and low
      density, in which the likelihood of social encounters is low, the costs of
      continuous scent-marking might exceed the associated fitness benefits; therefore,
      less intensive scent-marking only to signal presence to the opposite sex may be
      used. This hypothesis was tested in captivity with the Cabrera vole, a species
      with highly fragmented and low-density populations. Firstly, to assess the
      unknown scent-marking behaviour of the Cabrera voles, we conducted an assay
      wherein voles could scent-mark a clean substrate. Both sexes marked with urine
      and faeces, but never with anogenital secretions, and the amount of scent-marks
      was not different between sexes. In the subsequent assay, voles of each sex were
      given the choice of scent-mark on clean substrates or on substrates previously
      scent-marked by males or females. Both sexes marked with urine a larger area on
      substrates pre-marked by the opposite sex than on substrates pre-marked by the
      same-sex and clean substrates; however, no differences were found in the
      frequency of fecal boli deposited on the three types of substrate, and no
      anogenital secretions were found. The clear preference of receivers to scent-mark
      with urine the substrate pre-marked by the opposite sex strongly suggests that
      Cabrera voles use urine scent-marking for inter-sexual communication, probably to
      increase mate-finding likelihood, rather than for territorial defense and/or self
      advertisement.

PMID- 23537235
TI  - The defensive function of trichocysts in Paramecium tetraurelia against metazoan
      predators compared with the chemical defense of two species of toxin-containing
      ciliates.
AB  - The time-honored assumption about the defensive function of trichocysts in
      Paramecium against predators was recently verified experimentally against
      different species of unicellular predators. In the present study, we examined the
      defensive function of trichocysts against three metazoan predators, Cephalodella
      sp. (Rotifera), Eucypris sp. (Arthropoda), and Stenostomum sphagnetorum
      (Platyhelminthes). The results confirmed the defensive function of trichocysts
      against two of these metazoan predators (Cephalodella sp. and Eucypris sp.),
      while they seem ineffective against S. sphagnetorum. We also compared the
      defensive efficiency of the trichocysts of P. tetraurelia with that of toxin
      containing extrusomes of two ciliates.

PMID- 23537236
TI  - Sexual differences in post-hatching Saunders's gulls: size, locomotor activity,
      and foraging skill.
AB  - Various selection pressures induce the degree and direction of sexual size
      dimorphism in animals. Selection favors either larger males for contests over
      mates or resources, or smaller males are favored for maneuverability; whereas
      larger females are favored for higher fecundity, or smaller females for earlier
      maturation for reproduction. In the genus of Larus (seagulls), adult males are
      generally known to be larger in size than adult females. However, the ontogeny of
      sexual size dimorphism is not well understood, compared to that in adults. The
      present study investigates the ontogeny of sexual size dimorphism in Saunders's
      gulls (Larus saundersi) in captivity. We artificially incubated fresh eggs
      collected in Incheon, South Korea, and measured body size, locomotor activity,
      and foraging skill in post-hatching chicks in captivity. Our results indicated
      that the sexual differences in size and locomotor activity occurred with the post
      hatching development. Also, larger males exhibited greater foraging skills for
      food acquisition than smaller females at 200 days of age. Future studies should
      assess how the adaptive significance of the sexual size dimorphism in juveniles
      is linked with sexual divergence in survival rates, intrasexual contests, or
      parental effort in sexes.

PMID- 23537237
TI  - Spatial and temporal aspects of occurrence of Mogera species in the Japanese
      islands inferred from mitochondrial and nuclear gene sequences.
AB  - We assessed dispersal and vicariant events in four species of Japanese moles in
      the genera Mogera and Euroscaptor to better understand the factors shaping intra-
      and interspecific differentiation in Japanese moles. We used the combined
      viewpoints of molecular phylogeny and historical geology using nucleotide
      sequences of mitochondrial (cytochrome b; Cytb) and nuclear (A2ab, Bmp4, Tcf25,
      vWf) genes. The divergence times estimated from the molecular data were verified
      with available geological data on the chronology of fluctuations in sea level in
      the Korea Strait, assuming sequential migration and speciation events. This
      produced possible migration times of 5.6, 3.5, 2.4, and 1.3 million years ago for
      four species of Japanese moles, Euroscaptor mizura, Mogera tokudae, M. imaizumii,
      and M. wogura, respectively. For the western Japanese mole M. wogura, Cytb
      sequences revealed four major phylogroups with strong geographic affinities in
      southwestern Central Honshu (I), western Honshu/Shikoku (II), Kyushu/westernmost
      Honshu (III), and Korea/Russian Primorye (IV). The nuclear gene sequences
      supported the distinctiveness of phylogroups I and IV, indicating long,
      independent evolutionary histories. In contrast, phylogroups II and III were
      merged into a single geographic group based on the nuclear gene data.
      Intraspecific divergences in M. imaizumii and M. tokudae were rather apparent in
      Cytb but not in nuclear gene sequences. The results suggest that repeated
      dispersal events have occurred between the Asian continent and the Japanese
      Islands, and intensive vicariant events associated with abiotic and biotic
      factors have created higher levels of species and genetic diversities in moles
      occurring on the Japanese Islands.

PMID- 23537238
TI  - Geographic distributions of sexual and parthenogenetic forms of the weevil
      Scepticus insularis (Coleoptera: Curculionidae) in Japan.
AB  - Geographic ranges of parthenogenetic animals often differ from those of their
      sexual conspecifics, providing valuable information about evolutionary histories.
      We studied the geographic distributions of sexual and parthenogenetic forms of
      the weevil Scepticus insularis (Roelofs) (Coleoptera, Curculionidae) on Honshu,
      Shikoku, and Kyushu Islands, Japan. We collected Scepticus insularis at 18 sites
      in the northern half of Honshu; sequenced 633 bp of the mitochondrial ND2 (NADH
      dehydrogenase subunit 2) gene for 102 Honshu beetles; and constructed a ML gene
      tree based on these sequences and sequences previously reported for 104
      conspecific beetles from Hokkaido of known reproductive mode. The ND2 haplotypes
      fell into two distinct clades (I and II) separated by 9.5% nucleotide sequence
      divergence. The haplotypes from all parthenogenetic females on Hokkaido and those
      from all-female populations on Honshu invariably belonged to clade I, whereas
      sexual females on Hokkaido and some of the females in male/female populations on
      Honshu belonged to clade II. Haplotypes of males were in clade II, except for two
      Hokkaido males having a clade-I haplotype. Excluding these two enigmatic males,
      we treated individuals with clade-I haplotypes as parthenogenetic, and those with
      clade-II haplotypes as sexual. Parthenogenetic beetles were widespread throughout
      Hokkaido and central and northern Honshu, whereas sexuals were found only in
      three separate areas on Hokkaido and one on Honshu, often sympatrically with
      parthenogens. The distribution of S. insularis is congruent with the pattern
      termed geographic parthenogenesis.

PMID- 23537239
TI  - Sexual shape and size dimorphism in carabid beetles of the genus Ceroglossus: is
      geometric body size similar between sexes due to sex ratio?
AB  - Insects in many species vary greatly in the expression of secondary sexual
      traits, resulting in sexual dimorphism, which has been proposed to be a
      consequence of differences in sexual selection. In this study, we analyze the
      occurrence of sexual shape dimorphism and the correlation between geometric body
      size in males and females and sex ratio in the genus Ceroglossus (Coleoptera:
      Carabidae) using geometric morphometrics and randomization analysis. Our results
      show a positive relationship between the centroid size of males and females and
      sex ratio. However, we also observed a trend to maintain a "similar" body shape
      between sexes and species due to characteristics associated with sexual selection
      of the group in which the scarcity of outstanding morphological characters does
      not restrict reproduction capacity. The trend in sexual proportions was found to
      be near 1:1 for the eight species. We propose that the observed differences
      between sexes associated with the sex ratio are due to an energy cost caused by
      sexual selection; nevertheless, since proportions are similar for all the
      species, it is really not relevant to generate more conspicuous structures for a
      stronger male-male competence.

PMID- 23537240
TI  - Effects of environmental factors on natural reproduction of the four major
      Chinese carps in the Yangtze River, China.
AB  - The four major Chinese carps are commercially important fish species with high
      production in China. However, their recruitment decreased sharply in the Yangtze
      River since the late 20(th) century. In the present study, to reveal the
      relationships between spawning activities of the four species and environmental
      factors, drifting eggs were collected at Yidu City, in the middle reaches of the
      Yangtze River, from May to July each year between 2005 and 2010. Classification
      and regression trees (CART) analysis was applied to identify the key factors
      associated with spawning activities of the four carp species. Twelve predictor
      variables (hydrological and meteorological variables) and one response variable
      (egg presence or number of egg) were included in the CART. Our CART analysis
      showed that water temperature and the diurnal increase of water level were the
      two most significant factors for the spawning activities. When water temperature
      was between 18 degrees C and 24 degrees C, especially in association with the
      diurnal increase of water level greater than 0.55 m.d(-1), spawning activities
      was always favored. Unlike the hydrological factors, meteorological factors
      seemed to have no influence on initiating the spawning activities. The density of
      drifting eggs of the four species was mainly influenced by the diurnal variation
      of water level, the diurnal variation of water discharge, water temperature,
      humidity, and air pressure. We then related our results to the ecological
      regulation of the Three Gorge Reservoir in the middle reaches of the Yangtze
      River. We suggested that, when water temperature was between 18-24 degrees C from
      May to July, to ensure the successful spawning of the four carp species, the
      ecological regulation should be managed to create flood peaks and make the
      diurnal increase of water level greater than 0.55 m.d(-1).

PMID- 23537241
TI  - Small geographic variation in photoperiodic entrainment of the circannual rhythm
      in the varied carpet beetle, Anthrenus verbasci.
AB  - The circannual pupation rhythm of Anthrenus verbasci is entrained to an
      environmental cycle by changes in photoperiod. Exposure of larvae reared under
      short-day conditions to long days induced a clear phase delay of the circannual
      rhythm. There was no notable difference in the initial phase or period of the
      circannual rhythm among four geographically distinct populations of A. verbasci
      in Japan: Takanabe (32.1 degrees N), Osaka (34.7 degrees N), Sendai (38.3 degrees
      N), and Sapporo (43.1 degrees N) populations. The range of photoperiodic changes
      effective for phase delay in the circannual pupation rhythm was compared among
      the four populations. Although larvae did not show a typical threshold response,
      but responded quantitatively to the photophase duration in intermediate
      conditions, the critical daylengths were calculated as those under which the
      pupation was delayed by 50%: 12.8 h in the Takanabe population, 13.2 h in the
      Osaka population, and 13.6 h in the Sendai and Sapporo populations. Thus, the
      critical daylength for entrainment of the circannual rhythm in A. verbasci was
      correlated to the habitat latitude, but the differences among the populations
      were much smaller than those reported in photoperiodism for induction of diapause
      in various insects. Consequently, the difference in the pupation time among the
      four geographic populations was very small under the natural photoperiod in Osaka
      at 20 degrees C, and absent under the natural photoperiod and temperature in
      Osaka. These results suggest that A. verbasci survives and successfully produces
      the next generation in different geographic regions without changing the
      parameters of the circannual rhythm.

PMID- 23537242
TI  - Two novel gonadotropin-releasing hormones (GnRHs) from the urochordate ascidian,
      Halocynthia roretzi: implications for the origin of vertebrate GnRH isoforms.
AB  - Three forms of gonadotropin-releasing hormone (GnRH) are found in vertebrates;
      these differ in amino acid sequence, localization, distribution, and
      embryological origin. We used northern blot analysis, and in situ hybridization
      to detect GnRH transcripts in various tissues in the large ascidian Halocynthia
      roretzi. We cloned a cDNA encoding two novel GnRHs, termed tGnRH-10 and tGnRH-11,
      from H. roretzi, with deduced amino acid sequences of QHWSYGFSPG and QHWSYGFLPG,
      respectively. Both GnRHs are highly similar to those of teleosts and tetrapods.
      For example, the tGnRH-10 sequence is 90% identical to seabream GnRH1, and tGnRH
      11 is 90% identical to salmon GnRH3. The primary structure of the deduced
      preprotein is similar to that of chordate GnRHs and consists of a signal peptide,
      two decapeptides, up- and downstream processing sequences (containing lysine and
      arginine), and a GnRH-associated peptide. The transcripts of the H. roretzi GnRH
      gene were expressed in all tissues examined. Comparison of the signal peptide of
      the lamprey GnRH-II precursor with those of three forms from representative
      vertebrates revealed homology to GnRH2 precursors. These novel ascidian GnRHs
      offer a new perspective on the origin of vertebrate GnRH subtypes. We hypothesize
      that gnathostome GnRH2 was derived only from lamprey GnRH-II and that ancestral
      gnathostome GnRH, which produces neurons that originate in peripheral organs,
      gave rise to vertebrate GnRH1 and GnRH3 through whole-genome duplication.

PMID- 23537243
TI  - General morphology and innervation of the midgut and hindgut of Megalobulimus
      abbreviatus (Gastropoda, Pulmonata).
AB  - We describe the morphology and innervation of the midgut and hindgut of the giant
      land snail Megalobulimus abbreviatus for the first time. The midgut (stomach and
      intestine) and hindgut (rectum and anus) are innervated by the subesophageal
      ganglia, through the gastrointestinal branch (originated from the visceral nerve)
      and the rectum-anal nerve, respectively. Backfilling through these nerves
      revealed neuronal bodies, mainly in the right parietal and visceral ganglia. The
      enteric plexuses of the midgut and hindgut are formed by extensive axonal
      networks and several neuronal somata arranged in clusters or as isolated cells.
      The gastrointestinal branch and the rectum-anal nerve directly innervate the
      enteric plexuses of the intestine and the hindgut, respectively. However, the
      outer wall of the stomach has a stomatogastric nervous system, which consists of
      four ganglia: stomatogastric, gastric, cardic, and pyloric. Fibers of the
      gastrointestinal branch project to these ganglia. Anterograde tracing from
      stomatogastric system ganglia revealed that the enteric plexus of the stomach is
      innervated only by these peripheral ganglia. Anterograde tracing of the
      gastrointestinal branch did not result in labeling in the enteric plexus of the
      stomach. Therefore, the midgut and hindgut of M. abbreviatus is controlled by an
      intrinsic innervation, constituted by the submucous and myenteric plexuses, which
      are innervated directly by neurons from the subesophageal ganglia or indirectly
      via the stomatogastric nervous system (for the stomach).

PMID- 23537244
TI  - Cryptic diversity and host specificity in giant Xenos strepsipterans parasitic in
      large Vespa hornets.
AB  - Xenos is a strepsipteran genus whose members are parasitic to eusocial wasps,
      including the hornet genus Vespa. We undertook an extensive sampling of
      strepsipterans in Xenos from hornets collected in East Asia and performed
      molecular phylogenetic analyses based on mitochondrial cytochrome c oxidase
      subunit I gene sequences (652 bp) to investigate the cryptic diversity among 21
      individuals of strepsipterans. The analyses, accompanied by morphological
      examination, revealed that these strepsipterans represent two distinct species,
      X. moutoni du Buysson, 1903 and X. oxyodontes sp. nov. The two species differed
      in their host-utilization pattern: the latter was almost specific to Vespa analis
      and V. simillima, whereas the former was associated with other species in Vespa.

PMID- 23537246
TI  - Mapping the thermal behavior of DNA origami nanostructures.
AB  - Understanding the thermodynamic properties of complex DNA nanostructures,
      including rationally designed two- and three-dimensional (2D and 3D,
      respectively) DNA origami, facilitates more accurate spatiotemporal control and
      effective functionalization of the structures by other elements. In this work
      fluorescein and tetramethylrhodamine (TAMRA), a Forster resonance energy transfer
      (FRET) dye pair, were incorporated into selected staples within various 2D and 3D
      DNA origami structures. We monitored the temperature-dependent changes in FRET
      efficiency that occurred as the dye-labeled structures were annealed and melted
      and subsequently extracted information about the associative and dissociative
      behavior of the origami. In particular, we examined the effects of local and long
      range structural defects (omitted staple strands) on the thermal stability of
      common DNA origami structures. The results revealed a significant decrease in
      thermal stability of the structures in the vicinity of the defects, in contrast
      to the negligible long-range effects that were observed. Furthermore, we probed
      the global assembly and disassembly processes by comparing the thermal behavior
      of the FRET pair at several different positions. We demonstrated that the staple
      strands located in different areas of the structure all exhibit highly
      cooperative hybridization but have distinguishable melting temperatures depending
      on their positions. This work underscores the importance of understanding
      fundamental aspects of the self-assembly of DNA nanostructures and can be used to
      guide the design of more complicated DNA nanostructures, to optimize annealing
      protocol and manipulate functionalized DNA nanostructures.

PMID- 23537247
TI  - A community pharmacy weight management programme: an evaluation of effectiveness.
AB  - BACKGROUND: Community pharmacies may offer an accessible way of delivering weight
      management programmes but there have been few trials that use clinically
      significant weight loss outcomes, objective measures of weight and follow-up to
      12 months. We aimed to evaluate weight change among patients who used the
      Counterweight weight management programme delivered by community pharmacies.
      METHODS: The Counterweight Programme was introduced into community pharmacies in
      Fife, Scotland in 2009 for patients with a BMI >= 30 kg/m(2) or a BMI >= 2830
      kg/m(2) with a co-morbidity in localities in which Counterweight was not
      available at GP practices. The aim was to achieve an energy deficit of 500-600
      kcal per day. Counterweight specialist dietitians delivered training, support and
      patient information materials to community pharmacies. Patient weight was
      measured by pharmacy staff at each weight management session. Weight data
      recorded at each weight management session were used to estimate weight change
      and attendance at 3, 6 and 12 months. RESULTS: Between March 2009 and July 2012,
      458 patients were enrolled by the community pharmacies. Three-quarters of
      patients were women, mean age was 54 (SD 7.4) years and mean BMI 36.1 (SD 5.9)
      kg/m(2). Of 314 patients enrolled for at least 12 months, 32 (10.2% on an
      intention to treat basis) had achieved the target weight loss of >=5%; this was
      41.6% of those who attended at 12 months representing a mean weight loss of 4.1
      kg. Using Last Observation Carried Forward, 15.9% achieved the target weight loss
      within 12 months of enrolling. There was no significant effect of sex, baseline
      BMI or age on weight loss. CONCLUSIONS: The Counterweight pharmacy programme has
      a similar effectiveness to other primary care based weight management programmes
      and should be considered as part of a range of services available to a community
      to manage overweight and obesity.

PMID- 23537248
TI  - A clinical student exchange program organized by cardiothoracic department:
      feedback of participants.
AB  - BACKGROUND: The development of a student exchange program was an essential part
      of the cooperation between the Medical Schools of the University of Goettingen
      (Germany) and the University of Thrace in Alexandroupolis (Greece). The student
      exchange program started in 2008 and was performed once a year. The experiences
      of this program and the feedback of participants are presented. METHODS: Although
      organized by the Dept. of Thoracic, Cardiac, and Vascular Surgery, the approach
      of the program was multidisciplinary. Participants also attended Continuous
      Medical Education activities primary addressed to physicians. At the end of the
      program, the participants evaluated the program anonymously. The educational
      units were rated via a 4-grade system. Additionally, it was possible to comment
      both positive and negative aspects of the program. RESULTS: Twenty-nine
      educational units were evaluated. The practical teaching units yielded a better
      result than the classical teaching units (93% of practical units were evaluated
      as "very good" vs. 74% of lectures/seminars). The Continuous Medical Education
      activities were evaluated less favorable (only 61% were evaluated as "very
      good"). CONCLUSIONS: The student exchange program enhanced effective teaching and
      learning. Courses supporting practical medical skills were extremely positive
      evaluated. Continuous Medical Education activities are not suitable for students
      and therefore, we do not include such an event anymore. Additionally, the program
      created an excellent forum for contact and communication between the students of
      the two universities.

PMID- 23537249
TI  - Spirocyclic beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)
      inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid beta in a
      higher species.
AB  - A hallmark of Alzheimer's disease is the brain deposition of amyloid beta
      (Abeta), a peptide of 36-43 amino acids that is likely a primary driver of
      neurodegeneration. Abeta is produced by the sequential cleavage of APP by BACE1
      and gamma-secretase; therefore, inhibition of BACE1 represents an attractive
      therapeutic target to slow or prevent Alzheimer's disease. Herein we describe
      BACE1 inhibitors with limited molecular flexibility and molecular weight that
      decrease CSF Abeta in vivo, despite efflux. Starting with spirocycle 1a, we
      explore structure-activity relationships of core changes, P3 moieties, and Asp
      binding functional groups in order to optimize BACE1 affinity, cathepsin D
      selectivity, and blood-brain barrier (BBB) penetration. Using wild type guinea
      pig and rat, we demonstrate a PK/PD relationship between free drug concentrations
      in the brain and CSF Abeta lowering. Optimization of brain exposure led to the
      discovery of (R)-50 which reduced CSF Abeta in rodents and in monkey.

PMID- 23537251
TI  - Rejuvenation time.

PMID- 23537250
TI  - Multi-parametric MRI as an indirect evaluation tool of the mechanical properties
      of in-vitro cardiac tissues.
AB  - BACKGROUND: Early detection of heart failure is essential to effectively reduce
      related mortality. The quantification of the mechanical properties of the
      myocardium, a primordial indicator of the viability of the cardiac tissue, is a
      key element in patient's care. Despite an incremental utilization of multi
      parametric magnetic resonance imaging (MRI) for cardiac tissue characteristics
      and function, the link between multi-parametric MRI and the mechanical properties
      of the heart has not been established. We sought to determine the parametric
      relationship between the myocardial mechanical properties and the MR parameters.
      The specific aim was to develop a reproducible evaluative quantitative tool of
      the mechanical properties of cardiac tissue using multi-parametric MRI associated
      to principal component analysis. METHODS: Samples from porcine hearts were
      submitted to a multi-parametric MRI acquisition followed by a uniaxial tensile
      test. Multi linear regressions were performed between dependent (Young's modulus
      E) and independent (relaxation times T1, T2 and T2*, magnetization transfer ratio
      MTR, apparent diffusion coefficient ADC and fractional anisotropy FA) variables.
      A principal component analysis was used to convert the set of possibly correlated
      variables into a set of linearly uncorrelated variables. RESULTS: Values of 46.1
      +/- 12.7 MPa for E, 729 +/- 21 ms for T1, 61 +/- 6 ms for T2, 26 +/- 7 for T2*,
      35 +/- 5% for MTR x 100, 33.8 +/- 4.7 for FA x 10-2, and 5.85 +/- 0.21 mm2/s for
      ADC x 10-4 were measured. Multi linear regressions showed that only 45% of E can
      be explained by the MRI parameters. The principal component analysis reduced our
      seven variables to two principal components with a cumulative variability of 63%,
      which increased to 80% when considering the third principal component.
      CONCLUSIONS: The proposed multi-parametric MRI protocol associated to principal
      component analysis is a promising tool for the evaluation of mechanical
      properties within the left ventricle in the in vitro porcine model. Our in vitro
      experiments will now allow us focused in vivo testing on healthy and infracted
      hearts in order to determine useful quantitative MR-based biomarkers.

PMID- 23537254
TI  - Frostbite: prevention and initial management.
AB  - Frostbite is a local freezing injury that can cause tissue loss. Historically, it
      has been a disease of wars, but it is a hazard for anyone who ventures outdoors
      in cold weather. Frozen tissue is damaged both during freezing and rewarming.
      Frozen tissue is numb. Rewarming causes hyperemia and is often painful. Blisters
      and edema develop after rewarming. Hard eschar may form with healthy tissue deep
      to the eschar. Frostbite can be classified as superficial, without permanent
      tissue loss, or deep, with varying degrees of permanent tissue loss, often less
      than appearances suggest. It can be difficult to predict the amount of tissue
      loss at the time of presentation and early in the subsequent course. Prevention
      is better than treatment. It may be advisable not to rewarm frozen extremities in
      the field, but spontaneous thawing is often unavoidable. Extremities that have
      thawed should be protected from refreezing at all costs. Once in a protected
      environment, extremities that are still frozen should be rapidly thawed in warm
      water. Therapy with aspirin or ibuprofen may be helpful, but evidence is limited.
      Thrombolytic treatment within the first 24 hours after rewarming seems to be
      beneficial in some cases of severe frostbite. Prostacyclin therapy is very
      promising.

PMID- 23537255
TI  - Efficacy of residence at moderate versus low altitude on reducing acute mountain
      sickness in men following rapid ascent to 4300 m.
AB  - To determine if residence at moderate (~2000 m) compared to low (<50 m) altitude
      reduces acute mountain sickness (AMS) in men during subsequent rapid ascent to a
      higher altitude. Nine moderate-altitude residents (MAR) and 18 sea-level
      residents (SLR) completed the Environmental Symptoms Questionnaire (ESQ) at their
      respective baseline residence and again at 12, 24, 48, and 72 h at 4300 m to
      assess the severity and prevalence of AMS. AMS cerebral factor score (AMS-C) was
      calculated from the ESQ at each time point. AMS was judged to be present if AMS-C
      was >=0.7. Resting end-tidal CO2 (PETco2) and arterial oxygen saturation (Sao2)
      were assessed prior to and at 24, 48, and 72 h at 4300 m. Resting venous blood
      samples were collected prior to and at 72 h at 4300 m to estimate plasma volume
      (PV) changes. MAR compared to SLR: 1) AMS severity at 4300 was lower (p<0.05) at
      12 h (0.50+/-0.69 vs. 1.48+/-1.28), 24 h (0.15+/-0.19 vs. 1.39+/-1.19), 48 h
      (0.10+/-0.18 vs. 1.37+/-1.49) and 72 h (0.08+/-0.12 vs. 0.69+/-0.70); 2) AMS
      prevalence at 4300 was lower (p<0.05) at 12 h (22% vs. 72%), 24 h (0% vs. 56%),
      48 h (0% vs. 56%), and 72 h (0% vs. 45%); 3) resting Sao2 (%) was lower (p<0.05)
      at baseline (95+/-1 vs. 99+/-1) but higher (p<0.05) at 4300 at 24 h (86+/-2 vs.
      81+/-5), 48 h (88+/-3 vs. 83+/-6), and 72 h (88+/-2 vs. 83+/-5); and 4) PV (%)
      did not differ at 72 h at 4300 m in the MAR (4.5+/-6.7) but was reduced for the
      SLR (-8.1+/-10.4). These results suggest that ventilatory and hematological
      acclimatization acquired while living at moderate altitude, as indicated by a
      higher resting Sao2 and no reduction in PV during exposure to a higher altitude,
      is associated with greatly reduced AMS after rapid ascent to high altitude.

PMID- 23537256
TI  - Pulmonary vascular reserve and exercise capacity at sea level and at high
      altitude.
AB  - It has been suggested that increased pulmonary vascular reserve, as defined by
      reduced pulmonary vascular resistance (PVR) and increased pulmonary transit of
      agitated contrast measured by echocardiography, might be associated with
      increased exercise capacity. Thus, at altitude, where PVR is increased because of
      hypoxic vasoconstriction, a reduced pulmonary vascular reserve could contribute
      to reduced exercise capacity. Furthermore, a lower PVR could be associated with
      higher capillary blood volume and an increased lung diffusing capacity. We
      reviewed echocardiographic estimates of PVR and measurements of lung diffusing
      capacity for nitric oxide (DL(NO)) and for carbon monoxide (DL(CO)) at rest, and
      incremental cardiopulmonary exercise tests in 64 healthy subjects at sea level
      and during 4 different medical expeditions at altitudes around 5000 m. Altitude
      exposure was associated with a decrease in maximum oxygen uptake (VO2max), from
      42+/-10 to 32+/-8 mL/min/kg and increases in PVR, ventilatory equivalents for CO2
      (V(E)/VCO2), DL(NO), and DL(CO). By univariate linear regression VO2max at sea
      level and at altitude was associated with V(E)/VCO2 (p<0.001), mean pulmonary
      artery pressure (mPpa, p<0.05), stroke volume index (SVI, p<0.05), DL(NO)
      (p<0.02), and DL(CO) (p=0.05). By multivariable analysis, VO2max at sea level and
      at altitude was associated with V(E)/VCO2, mPpa, SVI, and DL(NO). The
      multivariable analysis also showed that the altitude-related decrease in VO2max
      was associated with increased PVR and V(E)/VCO2. These results suggest that
      pulmonary vascular reserve, defined by a combination of decreased PVR and
      increased DL(NO), allows for superior aerobic exercise capacity at a lower
      ventilatory cost, at sea level and at high altitude.

PMID- 23537257
TI  - Improved glycemic control in moderate altitude type II diabetic residents.
AB  - Exposure to altitude hypoxia may elicit changes in glucose homeostasis. This work
      is designated to investigate the glycemic control in type II diabetic patients
      (DMII) permanently resident at moderately high altitude (2400 m), and to
      investigate whether the arterial oxygen-related parameters are different in DMII
      patients living at altitude compared to those living at low altitude. Blood
      glucose, HbA1c, hemoglobin concentration, and hematocrit (HCT) were measured in
      moderate altitude type II diabetics and compared with both altitude nondiabetics
      and diabetic patients living at normoxic and normobaric conditions. The data
      revealed that fasting blood glucose was lower in altitude diabetic patients
      compared to diabetics living at low altitude (157+/-33 mg/dL and 176.81+/-15.98
      mg/dL, respectively, p<0.01). Also, glycemic control was improved in altitude
      diabetic patients, where their HbA1c was lower than the corresponding low
      altitude diabetic patients (8.68+/-0.79% and 9.30+/-1.02% respectively, p<0.01).
      Low oxygen tension at altitude was compensated in both diabetics and nondiabetics
      by a significant increase in both hemoglobin and HCT (17.33+/-0.72 mg/dL and
      50.7+/-2.20%, respectively) compared to the corresponding groups living at low
      levels (15.53+/-0.55 mg/dL and 45.8+/-1.64%, respectively). The underlying
      disease neither affected the arterial oxygen tension (PaO2) nor oxygen saturation
      (SaO2), where insignificant correlations were observed between glucose, PaO2 (r=
      0.06) and SaO2 (r=-0.2). These results suggest that moderate altitude may improve
      the glycemic control in type II diabetic patients compared to diabetics living at
      sea level.

PMID- 23537258
TI  - Lung function among 9- to 10-year-old Tibetan and Han Chinese schoolchildren
      living at different altitudes in Tibet.
AB  - Tibetans have lived at high altitude longer than any other high-altitude
      population. Still little is known about their lung function and especially among
      children. This study compared lung function values of forced vital capacity
      (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow
      at 50% of FVC (FEF50) in children living at various altitudes in Tibet and with
      different ancestries. A cross-sectional study of lung function was performed
      among 9-10-year-old native Tibetan and Han Chinese children living at 3700 meters
      above sea level, and among native Tibetan children living at 4300 meters above
      sea level. The adjusted FVC and FEV1 were significantly higher in Tibetan
      children living at 4300 m above sea level as compared to Tibetans living at 3700
      m. Tibetans living at 3700 m had higher FVC and FEV1 than Han Chinese living at
      the same altitude. All Tibetan children had on average higher FEF50 than Han
      Chinese. Tibetan children living at an altitude of 4300 m had relatively higher
      lung function than those living at 3700 m, and there were differences in lung
      function between Tibetans and Han Chinese who live at the same altitude. It seems
      likely that genetic factors involved in long-term adaptation to high altitude and
      cultural attributes could have contributed to the study findings.

PMID- 23537259
TI  - Prevalence of metabolic syndrome and common metabolic components in high altitude
      farmers and herdsmen at 3700 m in Tibet.
AB  - OBJECTIVES: To estimate the prevalence of metabolic syndrome, its associated
      factors and components in 30-80-year-old Tibetans living at high altitude.
      METHOD: Multistage sampling of 692 participants. We used IDF criteria for
      estimation of the metabolic syndrome, and a questionnaire based on the WHO MONICA
      protocol. RESULTS: The prevalence of metabolic syndrome was 8.2% (Confidence
      interval (CI):6.1-10.2) while the common components were: fasting hyperglycemia
      57.5% (53.8-61.1); abdominal obesity 46% (42.2-49.7); and high blood pressure 37%
      (33.4-40.5). Metabolic syndrome was significantly lower for males, those with
      higher education and physical activity >2000 Kcal/week. Self awareness, treatment
      and control were low for both diabetes and lipid abnormality. CONCLUSION: The
      overall prevalence of metabolic syndrome in high altitude farmers and herdsmen in
      Tibet was lower compared to other high altitude natives, while its components
      (hyperglycemia, obesity, and high blood pressure) were higher than in other high
      altitude communities. Implications of the findings of high prevalence of smoking
      (among men), obesity, and hypertension and low rates of awareness, treatment, and
      control of the components of the metabolic syndrome among rural highlanders
      propels the need for health programs targeting risk factors.

PMID- 23537260
TI  - Changes in cardiovascular functions, lipid profile, and body composition at high
      altitude in two different ethnic groups.
AB  - High altitude (HA) presents inhospitable environmental conditions that adversely
      affects human physiology and metabolism. Changes in physiological functions are
      reported during high altitude exposure, but the changes vary with physical state,
      culture habits, geographical locations, and genetic variation of individual. The
      present study was carried out to explore the variation in acclimatization pattern
      of two different ethnic groups in relation to cardiovascular functions, lipid
      profile and body composition. The study was carried out on 30 human volunteers
      (20 Indian and 10 Kyrgyz) initially at Bishkek for basal recording and on day 3,
      7, 14, and 21 of high altitude (3200 m) induction and again on day 3 of de
      induction. On altitude exposure significant decrease in body weight was observed
      both in Indian (day 14, p<0.001) and Kyrgyz (day 3, p<0.01) subjects. Decreased
      levels of total body water, extra cellular and intra cellular body water were
      also observed in both the groups. Significant reduction in body mass index
      (p<0.01), fat free mass (p<0.01), body cell mass (p<0.01) and body volume
      (p<0.01) was also observed in Kyrgyz subjects, whereas in Indian subjects the
      changes were not significant in these variables on high altitude exposure.
      Diastolic blood pressure and heart rate increased significantly on day 3 (p<0.001
      and p<0.01, respectively) of induction in Indian subjects; whereas in Kyrgyz
      significant increase was observed on day 14 (p<0.05) in both the cases. High
      density lipoprotein (HDL) cholesterol levels increased significantly on day 7 of
      HA exposure in both the groups. Results indicate that the Indian and Kyrgyz
      groups report differently, in relation to changes in cardiovascular functions,
      lipid profiles, and body composition, when exposed to HA. The difference observed
      in acclimatization pattern in the two groups may be due to ethnic/genetic
      variation of two populations.

PMID- 23537262
TI  - Protective effect of ginkgolide B on high altitude cerebral edema of rats.
AB  - Ginkgolide B (GB) is one of the ginkgolides isolated from leaves of the Ginkgo
      biloba tree. The aim of this study was to investigate whether GB has a protective
      effect on high altitude cerebral edema (HACE) of rats. HACE was induced by
      hypobaric hypoxia exposure for 24 hours in an animal decompression chamber with
      the chamber pressure of 267 mmHg to simulate an altitude of 8000 m. Before the
      exposure, three doses (3, 6, and 12 mg.kg(-1)) of GB were given intraperitoneally
      (ip) daily for 3 days. Effects of GB on brain water content (BWC), activity of
      superoxide dismutase (SOD), concentration of glutathione (GSH) and
      malondialdehyde (MDA), expression of active caspase-3 and poly(ADP-ribose)
      polymerase (PARP) were measured. In GB pretreatment groups (6 and 12 mg.kg(-1),
      but not 3 mg.kg(-1)), BWC, the concentration of MDA, the expression of active
      caspase-3 and PARP were reduced significantly, while the activity of SOD and
      concentration of GSH were significantly increased. In conclusion, these results
      indicate that GB has a protective effect on cerebral edema caused by high
      altitude in rats. The protective effect of GB might be attributed to its
      antioxidant properties and suppression of the caspase-dependent apoptosis
      pathway.

PMID- 23537261
TI  - Sustained exposure to cytokines and hypoxia enhances excitability of oxygen
      sensitive type I cells in rat carotid body: correlation with the expression of
      HIF-1alpha protein and adrenomedullin.
AB  - Recent studies in our laboratory demonstrated that chronic hypoxia (CH) induces a
      localized inflammatory response in rat carotid body that is characterized by
      macrophage invasion and increased expression of inflammatory cytokines. Moreover,
      CH-induced increased hypoxic sensitivity is blocked by concurrent treatment with
      the common anti-inflammatory drugs, ibuprofen and dexamethasone. The present
      study examines the hypothesis that selected cytokines enhance the excitability of
      oxygen-sensitive type I cells in the carotid body, and that downstream effects of
      cytokines involve upregulation of the transcription factor, hypoxia inducible
      factor-1alpha (HIF-1alpha). Cultured type I cells were exposed for 24 h to
      hypoxia and/or a cocktail of cytokines consisting of interleukin-1beta,
      interleukin-6, and tumor necrosis factor-alpha. Subsequent evaluation of hypoxia
      evoked intracellular Ca(2+)-responses showed that previous exposure to cytokines
      plus hypoxia resulted in a 110% (p<0.001) increase in cell excitability, whereas
      exposure to cytokines or hypoxia alone elicited smaller increases of 22% (not
      significant) and 35% (p<0.01), respectively. These changes were correlated with
      increased immunostaining for HIF-1alpha in similarly treated type I cells, where
      exposure to cytokines plus hypoxia promoted the nuclear translocation of the
      transcription factor. Moreover, treatment with cytokines and/or hypoxia elevated
      the expression of the HIF-1-regulated gene, adrenomedullin. These in vitro
      results are supported by studies which show that elevated type I cell sensitivity
      following in vivo CH is blocked by concurrent treatment with ibuprofen. The data
      suggest that CH-induced adaptation in arterial chemoreceptors may in part be
      mediated by cytokine/hypoxia-induced upregulation of HIF-1alpha, and consequent
      enhanced expression of specific hypoxia-sensitive genes in type I cells.

PMID- 23537264
TI  - Angelo Mosso's experiments at very low barometric pressures.
AB  - In 1898, Angelo Mosso (1846-1910) used his low-pressure chambers to carry out
      some remarkable experiments that are not well known. Paul Bert (1833-1886) had
      previously demonstrated that the deleterious effects of high altitude were due to
      low PO2, but this conclusion was disputed by many of the eminent scientists of
      the day. Mosso believed that the physiological effects of high altitude were
      caused by a low PCO2 (acapnia) and he made a series of low-pressure chamber
      experiments to test this. In some studies he added oxygen to the air in the
      chambers so that he could study the effects of extreme hypobaria; in one
      experiment he survived a barometric pressure of only 192 mm Hg equivalent to an
      altitude of about 10,800 m. Some of his experiments were observed by his daughter
      Mimi who wrote a colorful account in her book dedicated to her father "Un
      cercatore d'ignoto" (A seeker of the unknown).

PMID- 23537263
TI  - Upregulation of cytoprotective defense mechanisms and hypoxia-responsive proteins
      imparts tolerance to acute hypobaric hypoxia.
AB  - Exposure to high altitude is a well-known environmental stress with physiological
      and metabolic consequences, with the major stressor being hypobaric hypoxia. The
      disruption in cellular homeostasis elicits several acute and chronic adaptations
      designed to diminish the stress imposed by the hypoxic insult. Highly conserved
      cellular machinery protects the myocardium from damage under reduced oxygen
      tension. In the present study, adult Sprague-Dawley rats were exposed to an
      altitude of 9754 m in a decompression chamber and screened on the basis of the
      time taken for onset of gasping. The animals were grouped as susceptible (<10
      min), normal (10-25 min), and tolerant (>25 min). Histologically, susceptible
      animals showed increased myocardial inflammation and infiltration and greater CK
      MB activity. These animals showed a three-fold increase in reactive oxygen
      species levels and subsequent oxidative damage to proteins and lipids as compared
      to control unexposed group. In tolerant animals, the damage was minimal. The
      resistance to damage in these animals was possibly due to enhanced myocardial
      antioxidant enzymes, catalase and superoxide dismutase. A significantly higher
      expression of HIF-1alpha and its responsive genes, including EPO, HO-1, and
      GLUT1, was seen in tolerant animals, although VEGF expression was enhanced in the
      susceptible group. Cytoprotective chaperones, HSP70 and HSP90, were elevated in
      the tolerant animals. The differential expression of these hypoxia-responsive
      molecules may thus act as potential biochemical markers for screening and
      identifying individuals susceptible to environmental stress.

PMID- 23537267
TI  - Acetazolamide for the prevention of acute mountain sickness: time to move on.

PMID- 23537268
TI  - Variations in pulse oximetry at high altitude.

PMID- 23537269
TI  - Characteristics of patients with severe heart failure exhibiting exercise
      oscillatory ventilation.
AB  - This study aims to elucidate the characteristics of patients with severe
      nonischemic heart failure exhibiting exercise oscillatory ventilation (EOV) and
      the association of these characteristics with the subjective dyspnea. Forty-six
      patients with nonischemic heart failure who were classified into the New York
      Heart Association (NYHA) functional class III underwent cardiopulmonary exercise
      testing (CPX) and were divided into two groups according to the presence or
      absence of EOV. We evaluated the patients by using the Specific Activity Scale
      (SAS), biochemical examination, echocardiographic evaluation, results of CPX and
      symptoms during CPX (Borg scale), and reasons for exercise termination. EOV was
      observed in 20 of 46 patients. The following characteristics were observed in
      patients with EOV as compared with those without EOV with statistically
      significant differences: more patients complaining dyspnea as the reason for
      exercise termination, lower SAS score, higher N-terminal pro-brain natriuretic
      peptide level, larger left atrial dimension and volume, left ventricular end
      diastolic volume, higher Borg scale score at rest and at the anerobic threshold,
      higher respiratory rate at rest and at peak exercise, and higher slope of the
      minute ventilation-to-CO2 output ratio, and lower end-tidal CO2 pressure at peak
      exercise. Among the subjects with NYHA III nonischemic heart failure, more
      patients with EOV had a stronger feeling of dyspnea during exercise as compared
      with those without EOV, and the subjective dyspnea was an exercise-limiting
      factor in many cases.

PMID- 23537270
TI  - Effect of high shock number on acute complication development after
      extracorporeal shockwave lithotripsy.
AB  - PURPOSE: We assessed whether high shock number is associated with higher rates of
      acute complication development after extracorporeal shockwave lithotripsy (SWL).
      PATIENTS AND METHODS: A retrospective chart review of 372 patients who underwent
      436 SWL procedures at 24 kV using a Medstone STS-T lithotripter (Medstone
      International Inc., Aliso Viejo, CA) was conducted. Complications occurred within
      4 weeks of SWL. Treatments were split into three cohorts based on shock number
      (<2400, 2401-4000, and >4000). Postoperative sequelae of patients who were stone
      free and those with residual stone were studied separately. Chi-square tests were
      used to evaluate the relationship between shock number cohort and postoperative
      complication development. RESULTS: SWL treatments recorded for each cohort were
      158 (37.4%), 145 (34.4%), and 119 (28.2%), respectively. The short-term
      complication rate when SWL was successful was 8.3% overall. Complication rate for
      each cohort was 9.5% (11), 7.8% (5), and 7.2% (7), respectively. When SWL was
      successful, statistical analysis revealed no significant difference between
      complication rates and shock number cohort (P=0.63). Complications in patients
      with a residual stone occurred after 41.4% of treatments and trended upward with
      shock number cohort, but did not reach statistical significance (P=0.84).
      CONCLUSIONS: At high voltage, high shock number was not shown to cause higher
      rates of short-term postoperative complications, as experienced by patients, when
      SWL was successful or resulted in a residual stone, yet complication rates
      associated with residual stone burden were approximately five times as common.
      Forgoing a higher shock number in the presence of a residual stone may therefore
      increase the risks of sequelae immediately after SWL.

PMID- 23537271
TI  - The effects of hepatitis C virus core protein on the expression of miR-122 in
      vitro.
AB  - BACKGROUND: Hepatitis C virus (HCV) is one of the major pathogens of liver
      diseases. Some studies have previously reported that miR-122 can stimulate
      replication or translation of HCV. However, the effects of HCV infection on miR
      122 expression are not clear. The aim of this study was to investigate the
      effects of HCV core protein on the expression of miR-122 in a cell culture model.
      RESULTS: The miR-122 levels in Huh7.5.1 cells infected with HCV for different
      days or different HCV abundance were measured by real-time PCR. Significant
      decrease of miR-122 expression was found at late stage of infection and in the
      high-abundance group. Huh7.5.1 cells transfected with plasmid pEGFP-core or pEGFP
      were used to detect the effects of HCV core protein on miR-122 expression, the
      results showed that core protein could down-regulate the miR-122 expression level
      in a time- and dose- dependent manner, and reduced the susceptibility of Huh7.5.1
      cell to HCV. CONCLUSIONS: Down-regulating miR-122 expression by HCV core protein
      may give a new insight into the interaction between HCV and miR-122 and chronic
      HCV infection.

PMID- 23537272
TI  - Effect of compressive force on unbinding specific protein-ligand complexes with
      force spectroscopy.
AB  - Atomic force microscopy (AFM) is used extensively for the investigation of
      noncovalent molecular association. Although the technique is used to derive
      various types of information, in almost all instances the frequency of complex
      formation, the magnitude of rupture forces, and the shape of the force-distance
      curve are used to determine the behavior of the system. We have used AFM to
      consider the effect of contact force on the unbinding profiles of lactose
      galectin-3, as well as the control pairs lactose-KDPG aldolase, and mannose
      galectin-3, where the interacting species show negligible solution-phase
      affinity. Increased contact forces (>250 pN) resulted in increased probabilitites
      of binding and decreased blocking efficiencies for the cognate ligand-receptor
      pair lactose-G3. Increased contact force applied to two control systems with no
      known affinity, mannose-G3 and lactose-KDPG aldolase, resulted in nonspecific
      ruptures that were indistinguishable from those of specific lactose-G3
      interactions. These results demonstrate that careful experimental design is vital
      to the production of interpretable data, and suggest that contact force
      minimization is an effective technique for probing the unbinding forces and
      rupture lengths of only specific ligand-receptor interactions.

PMID- 23537273
TI  - Building nurse education capacity in India: insights from a faculty development
      programme in Andhra Pradesh.
AB  - BACKGROUND: India faces an acute shortage of nurses. Strategies to tackle the
      human resource crisis depend upon scaling up nursing education provision in a
      context where the social status and working conditions of nurses are highly
      variable. Several national and regional situation assessments have revealed
      significant concerns about educational governance, institutional and educator
      capacity, quality and standards. Improving educational capacity through nursing
      faculty development has been proposed as one of several strategies to address a
      complex health human resource situation. This paper describes and critically
      reflects upon the experience of one such faculty development programme in the
      state of Andhra Pradesh. DISCUSSION: The faculty development programme involved a
      2 year partnership between a UK university and 7 universities in Andhra Pradesh.
      It adopted a participatory approach and covered training and support in 4 areas:
      teaching, research/scholarship, leadership/management and clinical education.
      Senior hospital nurses were also invited to participate. SUMMARY: The programme
      was evaluated positively and some changes to educational practice were reported.
      However, several obstacles to wider change were identified. At the programme
      level, there was a need for more intensive individual and institutional
      mentorship as well as involvement of Indian Centres of Excellence in Nursing to
      provide local (as well as international) expertise. At the organisational level,
      the participating Colleges reported heavy workloads, lack of control over working
      conditions, lack of control over the curriculum and poor infra
      structure/resources as ongoing challenges. In the absence of wider educational
      reform in nursing and government commitment to the profession, faculty
      development programmes alone will have limited impact.

PMID- 23537274
TI  - Electrical and optical properties of Al-doped ZnO and ZnAl2O4 films prepared by
      atomic layer deposition.
AB  - ZnO/Al2O3 multilayers were prepared by alternating atomic layer deposition (ALD)
      at 150 degrees C using diethylzinc, trimethylaluminum, and water. The growth
      process, crystallinity, and electrical and optical properties of the multilayers
      were studied with a variety of the cycle ratios of ZnO and Al2O3 sublayers.
      Transparent conductive Al-doped ZnO films were prepared with the minimum
      resistivity of 2.4 * 10-3 Omega.cm at a low Al doping concentration of 2.26%.
      Photoluminescence spectroscopy in conjunction with X-ray diffraction analysis
      revealed that the thickness of ZnO sublayers plays an important role on the
      priority for selective crystallization of ZnAl2O4 and ZnO phases during high
      temperature annealing ZnO/Al2O3 multilayers. It was found that pure ZnAl2O4 film
      was synthesized by annealing the specific composite film containing alternative
      monocycle of ZnO and Al2O3 sublayers, which could only be deposited precisely by
      utilizing ALD technology.

PMID- 23537275
TI  - A statistical procedure to create a neighborhood socioeconomic index for health
      inequalities analysis.
AB  - INTRODUCTION: In order to study social health inequalities, contextual (or
      ecologic) data may constitute an appropriate alternative to individual
      socioeconomic characteristics. Indices can be used to summarize the multiple
      dimensions of the neighborhood socioeconomic status. This work proposes a
      statistical procedure to create a neighborhood socioeconomic index. METHODS: The
      study setting is composed of three French urban areas. Socioeconomic data at the
      census block scale come from the 1999 census. Successive principal components
      analyses are used to select variables and create the index. Both metropolitan
      area-specific and global indices are tested and compared. Socioeconomic
      categories are drawn with hierarchical clustering as a reference to determine
      "optimal" thresholds able to create categories along a one-dimensional index.
      RESULTS: Among the twenty variables finally selected in the index, 15 are common
      to the three metropolitan areas. The index explains at least 57% of the variance
      of these variables in each metropolitan area, with a contribution of more than
      80% of the 15 common variables. CONCLUSIONS: The proposed procedure is
      statistically justified and robust. It can be applied to multiple geographical
      areas or socioeconomic variables and provides meaningful information to public
      health bodies. We highlight the importance of the classification method. We
      propose an R package in order to use this procedure.

PMID- 23537276
TI  - Expression of interleukin (IL)-10, IL-17A and IL-22 in serum and sputum of stable
      chronic obstructive pulmonary disease patients.
AB  - Interleukin (IL)-17A, IL-22 and IL-10 have been implicated in the development of
      chronic obstructive pulmonary disease (COPD), but their expression in COPD is
      uncertain. Here we investigate the expression of IL-17A, IL-22 and IL-10 in the
      serum and sputum of COPD patients. Blood samples and induced sputum samples were
      collected from 94 patients with COPD, 23 healthy smokers, and 22 healthy control
      non-smokers. IL-17A, IL-22 and IL-10 were measured by enzyme-linked immunosorbent
      assay (ELISA). We found that: 1) serum and sputum IL-17A were higher in COPD
      compared to healthy smokers and non-smokers; 2) serum IL-17A increased with COPD
      stages, it was inversely correlated with percentage of forced expiratory volume
      in the first second (FEV1%) reference and positively correlated with C-reactive
      protein (CRP), Sputum IL-17A levels in the severe COPD patients were positively
      correlated with sputum neutrophils, and reversely correlated with sputum
      macraphages (p < 0.01); 3) serum and sputum IL-22 were significantly higher in
      COPD and healthy smokers than those in the non-smoker group, sputum IL-22 was
      similar in severe COPD (stage III and IV), which were higher than those in the
      other groups (p < 0.05); and, 4) serum and sputum IL-10 were similiar in COPD and
      healthy smokers, which were decreased compared to non-smokers. These data suggest
      that the increased level of IL-17A in serum and sputum plays important roles in
      the pathogenesis of COPD. The increased sputum IL-22 might also play important
      roles in the pathogenesis of COPD, while IL-10 secretion might be not only
      affected by COPD but also by cigarette smoke.

PMID- 23537277
TI  - Photosystem II does not possess a simple excitation energy funnel: time-resolved
      fluorescence spectroscopy meets theory.
AB  - The experimentally obtained time-resolved fluorescence spectra of photosystem II
      (PS II) core complexes, purified from a thermophilic cyanobacterium
      Thermosynechococcus vulcanus, at 5-180 K are compared with simulations. Dynamic
      localization effects of excitons are treated implicitly by introducing exciton
      domains of strongly coupled pigments. Exciton relaxations within a domain and
      exciton transfers between domains are treated on the basis of Redfield theory and
      generalized Forster theory, respectively. The excitonic couplings between the
      pigments are calculated by a quantum chemical/electrostatic method (Poisson
      TrEsp). Starting with previously published values, a refined set of site energies
      of the pigments is obtained through optimization cycles of the fits of stationary
      optical spectra of PS II. Satisfactorily agreement between the experimental and
      simulated spectra is obtained for the absorption spectrum including its
      temperature dependence and the linear dichroism spectrum of PS II core complexes
      (PS II-CC). Furthermore, the refined site energies well reproduce the temperature
      dependence of the time-resolved fluorescence spectrum of PS II-CC, which is
      characterized by the emergence of a 695 nm fluorescence peak upon cooling down to
      77 K and the decrease of its relative intensity upon further cooling below 77 K.
      The blue shift of the fluorescence band upon cooling below 77 K is explained by
      the existence of two red-shifted chlorophyll pools emitting at around 685 and 695
      nm. The former pool is assigned to Chl45 or Chl43 in CP43 (Chl numbering
      according to the nomenclature of Loll et al. Nature2005, 438, 1040) while the
      latter is assigned to Chl29 in CP47. The 695 nm emitting chlorophyll is suggested
      to attract excitations from the peripheral light-harvesting complexes and might
      also be involved in photoprotection.

PMID- 23537278
TI  - Apoptotic induction by anti-CD20 antibodies in chronic lymphocytic leukemia:
      comparison of rituximab and obinutuzumab.

PMID- 23537280
TI  - Preventing food allergy: protocol for a rapid systematic review.
AB  - BACKGROUND: The European Academy of Allergy and Clinical Immunology is developing
      guidelines about how to prevent and manage food allergy. As part of the
      guidelines development process, a systematic review is planned to examine
      published research about the prevention of food allergy. This systematic review
      is one of seven inter-linked evidence syntheses that are being undertaken in
      order to provide a state-of-the-art synopsis of the current evidence base in
      relation to epidemiology, prevention, diagnosis and clinical management, and
      impact on quality of life, which will be used to inform clinical recommendations.
      The aim of this systematic review will be to assess the effectiveness of
      approaches for the primary prevention of food allergy. METHODS: Seven
      bibliographic databases will be searched from their inception to September 30,
      2012 for systematic reviews, randomized controlled trials, quasi-randomized
      controlled trials, controlled clinical trials, controlled before-and-after
      studies, interrupted time series and cohort studies. Cohort studies will be
      included due to an inability to randomize with interventions such as
      breastfeeding. Studies that focused on the development of either food
      sensitization (a proxy measure) or food allergy will also be eligible for
      inclusion. Studies will be critically appraised using the Critical Appraisal
      Skills Program and Cochrane Risk of Bias tools, as appropriate. DISCUSSION: There
      is a lack of rigorous evidence to support recommendations about how to prevent
      the development of food allergy. It would appear that it is important to see the
      prevention of food allergy in the context of individual, family and wider factors
      that may influence its development. There is much left to learn about preventing
      food allergy, and this is a priority given the high societal and healthcare costs
      involved. This systematic review will help to further this learning.

PMID- 23537281
TI  - Octanuclear {Ln(III)8}(Ln = Gd, Tb, Dy, Ho) macrocyclic complexes in a
      cyclooctadiene-like conformation: manifestation of slow relaxation of
      magnetization in the Dy(III) derivative.
AB  - The synthesis of a series of macrocyclic, isostructural octanuclear lanthanide
      complexes [Gd8 (LH2)4 (MU-Piv)4 (eta(2)-Piv)4 (MU-OMe)4].6CH3OH.2H2O (1), [Tb8
      (LH2)4 (MU-Piv)4 (eta(2)-Piv)4 (MU-OMe)4]4CH3OH.4H2O (2), [Dy8(LH2)4 (MU-Piv)4
      (eta(2)-Piv)4 (MU-OMe)4].8CH3OH (3), and [Ho8(LH2)4(MU-Piv)4 (eta(2)-Piv)4 (MU
      OMe)4].CH3OH.4H2O (4) have been achieved, using Ln(III) nitrate salts, pivalic
      acid, and a new multidentate chelating ligand (2E,N'E)-N'-(3-((bis(2-
      hydroxyethyl)amino)methyl)-2-hydroxy-5-methylbenzylidene)-2-(hydroxyimino)
      propane hydrazide (LH5), containing two unsymmetrically disposed arms; one side
      of the phenol unit is decorated with a diethanolamine group while the other side
      is a hydrazone that has been built by the condensation reaction involving 2
      hydroxyiminopropanehydrazide. All the compounds, 1-4, are neutral and are held by
      the four [LH2](3-) triply deprotonated chelating ligands. In these complexes all
      the lanthanide ions are doubly or triply bridged via phenolate, alkoxy, and
      pivalate oxygens. The metal centers are distributed over the 8 vertices of an
      octagon, resembling a cyclooctadiene ring core. The details of magnetochemical
      analysis for complexes 1-4 shows that they exhibit antiferromagnetic interactions
      between the Ln(3+) ions through the phenoxo, alkoxo, and pivalato bridging
      groups. None of the compounds exhibits slow relaxation of the magnetization at
      zero applied direct current (dc) magnetic field, which could be due to the
      existence of a fast quantum tunneling relaxation of the magnetization (QTM). In
      the case of 3, the application of a small dc field is enough as to fully or
      partly suppress the fast and efficient zero-field QTM allowing the observation of
      slow relaxation above 2 K.

PMID- 23537282
TI  - Intravitreal injection of triamcinolone acetonide into healthy rabbit eyes alters
      retinal function and morphology.
AB  - AIM: To study the effects of intravitreally injected triamcinolone acetonide (TA)
      and/or its preservative benzyl alcohol (BA) in healthy rabbit retina. METHODS:
      Forty-eight rabbits (aged 4 months, body weight ~3 kg) were randomized into four
      groups (n = 12). They were examined with electroretinography (ERG) prior to drug
      exposure, and then injected intravitreally with a combination of TA and BA, TA
      without BA, BA alone or a balanced saline solution (BSS). The electroretinograms
      were assessed 1 week and 7 weeks post-injection. The rabbits were euthanized and
      the sectioned retinas were studied. Immunohistochemical analysis was performed on
      rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Muller
      cells. RESULTS: Rabbits injected with BA showed a significantly lower rod
      mediated b-wave amplitude than the controls 1 week after injection. TA-injected
      rabbits demonstrated significantly higher a- and b-wave amplitudes in the total
      retinal response than the controls 1 week post-injection. The rabbits injected
      with TA + BA demonstrated a significantly higher b-wave amplitude in the total
      retinal response than the controls 1 week after injection. The significantly
      higher a-wave amplitude in the total retinal response remained in the TA-injected
      rabbits 7 weeks after injection. Immunohistochemistry revealed that protein
      kinase C alpha (PKC alpha) was down-regulated in both the perikarya and the axons
      of bipolar cells in histological sections from rabbit retina injected with TA +
      BA, BA and TA. CONCLUSIONS: Intravitreal injection of the preservative BA reduces
      the isolated rod-mediated retinal response in the rabbit, transiently and
      selectively. Intravitreal injection of TA increases the total retinal response in
      the rabbit up to seven weeks after injection. The effects observed are not only
      limited to retinal function, but also include changes in the expression of PKC
      alpha in rod bipolar cells, indicating drug-related interference with normal
      retinal physiology in the healthy rabbit eye.

PMID- 23537283
TI  - Prevalence of porcine enterovirus 9 in pigs in middle and eastern China.
AB  - Little information on the epidemiology and pathogenicity of porcine enterovirus 9
      (PEV-9) is available. The present study investigated the prevalence of PEV-9 in
      pig populations in middle and eastern China using reverse transcriptase (RT)-PCR.
      All 14 sampled farms were positive for PEV-9 and the overall prevalence of
      infection in the studied pigs was 8.3% (37/447). There was a higher frequency of
      infection in pigs aged 10-15 weeks (12/119, 10.1%) than in pigs aged >20 weeks
      (5/103, 4.9%). A 313 nucleotide sequence from the 5'-UTR region of 37 Chinese PEV
      9 positive samples had 96.1-100% sequence homology. On phylogenetic analysis,
      sequences clustered into two major groups, from which two representative strains
      were selected to determine the complete RNA-dependent RNA polymerase (RdRp) gene
      sequence. Phylogenetic analysis based on the RdRp gene suggested that PEV-9
      strains from China formed a new subgroup. Piglets were inoculated orally with the
      PEV-9 strain identified in this study. Although most experimental pigs showed no
      clinical signs, almost all carried PEV-9 in one or more tissues after 6 days post
      inoculation. The results of tissue histologic examination suggested that PEV9 can
      cause pathological changes in cerebrum and lung.

PMID- 23537284
TI  - Crystal structures of glycoside hydrolase family 3 beta-glucosidase 1 from
      Aspergillus aculeatus.
AB  - GH3 (glycoside hydrolase family 3) BGLs (beta-glucosidases) from filamentous
      fungi have been widely and commercially used for the supplementation of
      cellulases. AaBGL1 (Aspergillus aculeatus BGL1) belongs to the GH3 and shows high
      activity towards cellooligosaccharides up to high degree of polymerization. In
      the present study we determined the crystal structure of AaBGL1. In addition to
      the substrate-free structure, the structures of complexes with glucose and
      various inhibitors were determined. The structure of AaBGL1 is highly
      glycosylated with 88 monosaccharides (18 N-glycan chains) in the dimer. The
      largest N-glycan chain comprises ten monosaccharides and is one of the largest
      glycans ever observed in protein crystal structures. A prominent insertion region
      exists in a fibronectin type III domain, and this region extends to cover a wide
      surface area of the enzyme. The subsite +1 of AaBGL1 is highly hydrophobic. Three
      aromatic residues are present at subsite +1 and are located in short loop regions
      that are uniquely present in this enzyme. There is a long cleft extending from
      subsite +1, which appears to be suitable for binding long cellooligosaccharides.
      The crystal structures of AaBGL1 from the present study provide an important
      structural basis for the technical improvement of enzymatic cellulosic biomass
      conversion.

PMID- 23537285
TI  - Conformationally controlled oligocholate membrane transporters: learning through
      water play.
AB  - Controlled translocation of molecules and ions across lipid membranes is the
      basis of numerous biological functions. Because synthetic systems can help
      researchers understand the more complex biological ones, many chemists have
      developed synthetic mimics of biological transporters. Both systems need to deal
      with similar fundamental challenges. In addition to providing mechanistic
      insights into transport mechanisms, synthetic transporters are useful in a number
      of applications including separation, sensing, drug delivery, and catalysis. In
      this Account, we present several classes of membrane transporters constructed in
      our laboratory from a facially amphiphilic building block, cholic acid. Our
      "molecular baskets" can selectively shuttle glucose across lipid membranes
      without transporting smaller sodium ions. We have also built oligocholate
      foldamers that transiently fold into helices with internal hydrophilic binding
      pockets to transport polar guests. Lastly, we describe amphiphilic macrocycles,
      which form transmembrane nanopores in lipid bilayers through the strong
      associative interactions of encapsulated water molecules. In addition to
      presenting the different transport properties of these oligocholate transporters,
      we illustrate how fundamental studies of molecular behavior in solution
      facilitate the creation of new and useful membrane transporters, despite the
      large difference between the two environments. We highlight the strong
      conformational effect of transporters. Because the conformation of a molecule
      often alters its size and shape, and the distribution of functional groups,
      conformational control can be used rationally to tune the property of a
      transporter. Finally, we emphasize that, whenever water is the solvent, its
      unique properties--small size, strong solvation for ionic functionalities, and an
      extraordinary cohesive energy density (i.e., total intermolecular interactions
      per unit volume)--tend to become critical factors to be considered. Purposeful
      exploitation of these solvent properties may be essential to the success of the
      supramolecular process involved--this is also the reason for the "learning
      through water play" in the title of this Account.

PMID- 23537286
TI  - Agreement between pre-post measures of change and transition ratings as well as
      then-tests.
AB  - BACKGROUND: Different approaches have been developed for measuring change. Direct
      measurement of change (transition ratings) requires asking a patient directly
      about his judgment about the change he has experienced (reported change). With
      indirect measures of change, the patients' status is assessed at different time
      points and differences between them are calculated (measured change). When using
      the quasi-indirect approach ('then-test'), patients are asked after an
      intervention to rate their statuses both before the intervention as well as at
      the time of the enquiry. Associations previous studies have found between the
      different approaches might be biased because transition ratings are generally
      assessed using a single, general item, while indirect measures of change are
      generally based on multi-item scales. We aimed to quantify the agreement between
      indirect and direct as well as indirect and quasi-indirect measures of change
      while using multi-item scales exclusively. We explored possible reasons for non
      agreement (present-state bias, recall bias). METHODS: We re-analysed a data set
      originally collected to investigate the prognostic validity of different
      approaches of change measurements. Patients from a 3-week inpatient
      rehabilitation programme for either cardiac or musculoskeletal disorders filled
      in health-status questionnaires (which included scales for sleep function,
      physical function, and somatisation) both at admission and at discharge. The
      patients were then randomised to receive either an additional transition-rating
      or then-test questionnaire at discharge. RESULTS: Out of 426 patients, 395
      (92.7%) completed all questionnaires. Correlation coefficients between indirect
      and quasi-indirect measures of change ranged from r = .60 to r = .71, compared to
      r = .37 to r = .48 between indirect and direct measures of change. Correlation
      coefficients between pre-test and retrospective pre-test (then-test) results
      ranged from r = .69 to r = .82, indicating a low level of recall bias. Pre-test
      variation accounted for a substantial amount of variance in transition ratings in
      addition to the post-test scores, indicating a low level of present-state bias.
      CONCLUSIONS: Indirect and quasi-indirect measurements of change yielded
      comparable results indicating that recall bias does not necessarily affect quasi
      indirect measurement of change. Quasi-indirect measurement might serve as a
      substitute for pre-post measurement under conditions still to be specified.
      Transition ratings reflect different aspects of change than indirect and quasi
      indirect methods do, but are not necessarily biased by patients' present states.

PMID- 23537289
TI  - An outbreak of norovirus gastroenteritis associated with a secondary water supply
      system in a factory in south China.
AB  - BACKGROUND: Between September 17 and October 3, 2009, hundreds of workers
      employed in a manufacturing factory in Shenzhen, a city in south China developed
      a sudden onset of acute gastroenteritis. A retrospective cohort study is designed
      to identify the risk factors and control this outbreak. METHODS: Information on
      demographic characteristics, working place, the history of contact with a person
      having diarrhea and/or vomiting, drink water preference and frequency, eating in
      the company cafeteria or outside the company, hand-washing habits and eating
      habits is included. Furthermore, in order to find the contamination source, we
      investigated the environment around the underground reservoir and collected water
      samples from the junction between municipal supply water system and underground
      reservoir to test potential bacteria and virus, examine the seepage tracks on the
      wall of the underground reservoir from the side of septic tank, and check the
      integrity and attitude of this lid. Relative risk was presented and Chi-square
      test was performed. All the analyses were performed with OpenEpi software version
      2.3.1 online. RESULTS: The cohort study demonstrated that the workers who had
      direct drink water were 3.0 fold more likely to suffer from acute gastroenteritis
      than those who consumed commercial bottled water. The direct drinking water,
      water of the tank of buildings, and the underground reservoir were positive only
      for norovirus. Norovirus was also detected from stool and rectal swab samples
      from patients with acute gastroenteritis. The underground reservoir was found to
      be the primary contamination source. Further environmental investigation showed
      that the norovirus contaminated substance entered into the underground reservoir
      via access holes in lid covering this underground reservoir. CONCLUSION: This
      acute gastroenteritis outbreak was caused by the secondary supply system
      contaminated by norovirus in this factory. The outbreak of gastroenteritis cases
      caused by norovirus frequently occurred in China due to a lack of surveillance
      and supervision, and due to faults in the construction of such water systems.
      Therefore, more attentions should pay to the secondary supply water system in
      China.

PMID- 23537290
TI  - A +20% adjustment in the computed tomography measured ureteral length is an
      accurate predictor of true ureteral length before ureteral stent placement.
AB  - PURPOSE: The correct length of a ureteral stent is important in minimizing
      postplacement discomfort and stent migration. We describe and validate a method
      to accurately measure the ureteral length. MATERIALS AND METHODS: The ureteral
      length in 48 patients undergoing ureteral stent placement for urolithiasis was
      measured by computed tomography (CT) (total thickness of axial slices between the
      ureteropelvic junction and ureterovesical junction) and adjusted up by 20%. The
      adjusted CT measurement of ureteral length was compared with direct
      intraoperative measurement using scatter plot and Pearson correlation
      coefficient. Correlation coefficients were also calculated between intraoperative
      ureteral length and various body habitus measurements such as the height, weight,
      and waist circumference. RESULTS: Median patient age was 62 years. The median
      stone diameter was 7.5 mm (1-20). The ratio of left- to right-sided stones was
      2:1. The stone location was in the proximal ureter in 45.8%, distal ureter in
      37.5%, kidney in 10.4%, and midureter in 6.3%. Symptoms included adnominal/flank
      pain (93.8%) followed by nausea/vomiting (39.6%) and gross hematuria (16.7%).
      Median creatinine was 1.4 (0.8-3.6 mg/dl) and median WBC was 8.6 (2.8-17.6). The
      median ureteral length was 25.8 cm (19.2-29.4) on the CT scan and 25.5 cm (19.0
      29.0) on the intraoperative measurement (p=0.57). The Pearson correlation
      coefficient between the two measurements was 0.979. In contrast, the height,
      weight, and waist circumference correlated poorly with intraoperative ureteral
      length measurements (r=0.34, 0.19, and 0.40, respectively). CONCLUSION: CT
      measured ureteral length adjusted up by 20% is a reliable method to accurately
      measure the true ureteral length. This method is superior to traditional indirect
      methods that rely on body habitus measurements.

PMID- 23537287
TI  - Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II
      alpha gene status and protein expression in patients with breast cancer treated
      with anthracycline-containing adjuvant chemotherapy: pooled analysis of two
      Hellenic Cooperative Oncology Group (HeCOG) phase III trials.
AB  - BACKGROUND: The HER2 gene has been established as a valid biological marker for
      the treatment of breast cancer patients with trastuzumab and probably other
      agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated
      with response to anthracyclines. Limited information exists on the relationship
      of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with
      outcome of patients treated with anthracycline-containing adjuvant chemotherapy.
      METHODS: Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients
      with high-risk operable breast cancer, enrolled in two consecutive phase III
      trials, were assessed in a central laboratory by fluorescence in situ
      hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe).
      Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and
      >=2.0, respectively, or gene copy number higher than 6. Additionally, HER2,
      TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry
      (IHC) and patients were classified according to their IHC phenotype. Treatment
      consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy
      and radiation, as indicated. RESULTS: HER2 amplification was found in 23.7% of
      the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified
      tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and
      CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55),
      respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2
      amplification). Adjusting for treatment groups in the Cox model, HER2
      amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification
      were not associated with time to relapse or time to death. CONCLUSION: HER2
      amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification
      were not associated with outcome in high-risk breast cancer patients treated with
      anthracycline-based adjuvant chemotherapy. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and
      ACTRN12609001036202.

PMID- 23537291
TI  - Anthropometric differences among natives of Abuja living in urban and rural
      communities: correlations with other cardiovascular risk factors.
AB  - BACKGROUND: There is an increase of obesity and other cardiovascular risk factors
      worldwide, but especially in developing countries where multifaceted transitions
      are occurring. There is need for more evidence for the cardio-metabolic effect of
      changing lifestyles and urbanization in Nigeria. This study aimed at defining
      rural-urban differences in anthropometric parameters in two Nigerian communities
      of the same ancestral origin and to determine the cardiovascular risk correlates
      of these anthropometric measurements. This was a cross-sectional epidemiological
      study using stratified cluster sampling method. We studied 335 and 332 urban and
      rural dwellers respectively. A complete cardiovascular profile as well as
      anthropometric measurements was compared between the two populations. RESULTS:
      All anthropometric indices considered in this study (weight, BMI, waist
      circumference, waist circumference/height ratio, abdominal height; biceps,
      triceps, sub-scapular, abdominal, superior iliac skinfold thicknesses) were
      significantly higher in urban than in the rural population (p = <0.001).
      Overweight, obesity and hypertension were significantly prevalent among the urban
      population (p = <0.001) while there was no significant difference in the
      prevalence of dyslipidaemia (p = 0.096) and diabetes (p = 0.083) between the two
      cohorts. Females tend to have a higher chance of obesity than males although
      there was no gender difference in waist circumference and central skin fold
      thickness in the rural population. Age was the significant predictor of systolic
      blood pressure among the rural (R(2) = 0.157, beta = 0.258, p = 0.016) and urban
      female population (R(2) = 0.201, beta = 0.351, p = <0.001) while Abdominal height
      (R(2) = 0.16, beta = 0.281, p = 0.001) and waist circumference (R(2) = 0.064 beta
      = 0.064, p = .003) were predictors of systolic blood pressure in urban and rural
      men respectively. CONCLUSION: Anthropometric indices were significantly higher
      among the urban than the rural populations. Cardiovascular risks were equally
      more prevalent among the urban population. Appropriate health education and
      lifestyle modification strategies may reduce the increased burden of
      cardiovascular risk factors associated with rural-urban migration.

PMID- 23537292
TI  - Transient helical structure during PI3K and Fyn SH3 domain folding.
AB  - A growing list of proteins, including the beta-sheet-rich SH3 domain, is known to
      transiently populate a compact alpha-helical intermediate before settling into
      the native structure. Examples have been discovered in cryogenic solvent as well
      as by pressure jumps. Earlier studies of lambda repressor mutants showed that
      transient states with excess helix are robust in an all-alpha protein. Here we
      extend a previous study of src SH3 domain to two new SH3 sequences,
      phosphatidylinositol 3-kinase (PI3K) and a Fyn mutant, to see how robust such
      helix-rich transients are to sequence variations in this beta-sheet fold. We
      quantify helical structure by circular dichroism (CD), protein compactness by
      small-angle X-ray scattering (SAXS), and transient helical populations by cryo
      stopped-flow CD. Our results show that transient compact helix-rich intermediates
      are easily accessible on the folding landscape of different SH3 domains. In
      molecular dynamics simulations, force field errors are often blamed for transient
      non-native structure. We suggest that experimental examples of very fast alpha
      rich transient misfolding could become a more subtle test for further force field
      improvements than observation of the native state alone.

PMID- 23537293
TI  - Mandatory continuing professional development requirements: what does this mean
      for Australian nurses.
AB  - BACKGROUND: This paper presents a discussion related to the recent decision in
      Australia to introduce mandatory Continuing Professional Development (CPD) for
      nurses. Historically there has been international debate surrounding mandatory
      CPD requirements; this debate is ongoing as Australian nurses face a diverse
      range of CPD offerings from a variety of providers. DISCUSSION: The purpose of
      this paper is to examine how mandatory CPD requirements for national nursing
      registration in Australia have evolved and to present an analysis of what this
      will mean for Australian nurses. What is yet to be determined is how to measure
      professional development and the effectiveness of professional development
      education. This is important to the international community with consensus in the
      literature that professional development is linked to ongoing education.
      Contradicting arguments are presented about whether this professional development
      should be mandatory. SUMMARY: Presenting a contemporary discussion about the
      current and potential impact of mandatory CPD requirements for nurses, this
      discussion paper utilises the case of Australia's current national policy and CPD
      operation to examine the choices that nurses make in order to fulfil their
      legislative requirements. Additional arguments are presented about the barriers
      nurses face in undertaking CPD. The quest for effective CPD is complex and should
      incorporate different situations for nurses and individual learning styles.

PMID- 23537294
TI  - On the generalized Hartman effect presumption in semiconductors and photonic
      structures.
AB  - : We analyze different examples to show that the so-called generalized Hartman
      effect is an erroneous presumption. The results obtained for electron tunneling
      and transmission of electromagnetic waves through superlattices and Bragg
      gratings show clearly the resonant character of the phase time behavior so that a
      generalized Hartman effect is not expected to occur. A reinterpretation of the
      experimental results in double Bragg gratings is proposed.

PMID- 23537296
TI  - Time to steady state after changes in FIO(2) in patients with COPD.
AB  - BACKGROUND: International guidelines recommend that when changing FIO2 in
      patients with COPD receiving Long-Term Oxygen Therapy (LTOT), 30 minutes should
      be waited for steady state before measurement of arterial blood gasses. This
      study evaluates whether 30 minutes is really necessary, as a smaller duration
      might improve the logistics of care, potentially reducing the time spent by
      patients at the out-patient clinic. METHODS: 12 patients with severe to very
      severe COPD according to the GOLD guidelines were included. Patients had a median
      FEV1% of 23% of the predicted value (range 15-64%), median FEV1/FVC 0.43 (range
      0.26-0.63), and chronic respiratory failure necessitating LTOT, 1-4
      liters/minute, minimum 16 hours/day. Following a FIO2 reduction (wash out),
      arterial blood gases were measured at 0, 1, 2, 4, 8, 12, 17, 22, 32 and 34
      minutes. FIO2 was then increased to baseline levels (wash in) and blood gasses
      measured at 0, 1, 2, 4, 8, 12, 17, 22, 32, and 34 minutes. Data were analyzed to
      examine the dynamics of arterial PO2 and saturation (SO2) wash out and wash in by
      calculating the time constants, tau (o), and to evaluate the time required to
      reach values which might be considered clinically stable, defined as PO2 within
      0.5 kPa and SO2 within 1% of equilibrium values. RESULTS: For arterial PO2 values
      of time constants were about 3 minutes and similar for both wash out and wash in.
      A median of 5 minutes was required to reach clinically stable values of PO2 in
      both wash out and wash in, with 7-8 minutes sufficient in 75% of patients, and in
      the worst case 14 minutes. For SO2, values of the time constant were 4.5 and 1.4
      minutes for wash out and wash in, respectively. The time required to reach
      clinically stable values was different in the two phases. For wash out the median
      time was 7.4 minutes, and in the worst case 15.6 minutes. For wash in the median
      time was 2.6 minutes and in worst case 6.8 minutes. No significant changes in
      PCO2 or pH were seen during FIO2 changes. DISCUSSION/CONCLUSION: This study shows
      that oxygen equilibration relevant for clinical interpretation requires only 10
      minutes following an increase and 16 minutes following a decrease in FIO2. over
      the range studied.

PMID- 23537297
TI  - Is galectin-3 antibody a useful marker in the diagnosis of malignant pleural
      mesothelioma?
AB  - Malignant pleural mesothelioma (MPM) is a challenging diagnosis characterized by
      the absence of real specific diagnostic markers. Positivity with the galectin-3
      antibody was assessed by a cytoplasmic expression in 17 MPM. Fourteen cases
      expressed the galectin-3 antibody. The three negative cases consisted of
      epithelioid, biphasic, and sarcomatoid MPM. The 14 positive cases consisted of
      epithelioid MPM in 12 cases, sarcomatoid MPM in one case, and biphasic MPM in one
      case. In spite of our inability to prove the real diagnostic value of the
      galectin-3 antibody, our findings make us wonder about the implication of this
      antibody in the carcinogenesis of MPM.

PMID- 23537295
TI  - Short-term single treatment of chemotherapy results in the enrichment of ovarian
      cancer stem cell-like cells leading to an increased tumor burden.
AB  - Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of
      disease recurrence due to failure of chemotherapy treatment. In this study, using
      two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY)
      we demonstrate enrichment in a population of cells with high expression of CSC
      markers at the protein and mRNA levels in response to cisplatin, paclitaxel and
      the combination of both. We also demonstrate a significant enhancement in the
      sphere forming abilities of ovarian cancer cells in response to chemotherapy
      drugs. The results of these in vitro findings are supported by in vivo mouse
      xenograft models in which intraperitoneal transplantation of cisplatin or
      paclitaxel-treated residual HEY cells generated significantly higher tumor burden
      compared to control untreated cells. Both the treated and untreated cells
      infiltrated the organs of the abdominal cavity. In addition, immunohistochemical
      studies on mouse tumors injected with cisplatin or paclitaxel treated residual
      cells displayed higher staining for the proliferative antigen Ki67, oncogeneic
      CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and
      CD117, compared to mice injected with control untreated cells. These results
      suggest that a short-term single treatment of chemotherapy leaves residual cells
      that are enriched in CSC-like traits, resulting in an increased metastatic
      potential. The novel findings in this study are important in understanding the
      early molecular mechanisms by which chemoresistance and subsequent relapse may be
      triggered after the first line of chemotherapy treatment.

PMID- 23537298
TI  - Study of association between HLA-DR4 and DR53 and autoantibody detection in
      rheumatoid arthritis.
AB  - The present study explored the association between human leukocyte antigen (HLA)
      DR4, DR53, and auto antibodies in rheumatoid arthritis (RA) and its clinical
      significance. A total of 305 patients with RA and 50 healthy subjects who
      underwent medical examination were evaluated. HLA-DR4 and HLA-DR53 and auto
      antibodies were detected. The results showed that frequencies of HLA-DR4 and HLA
      DR53 alleles in RA patients were 42.95% and 54.75%, respectively, which were
      significantly different from those in control group (p < 0.01). Frequencies of
      anti-cyclic citrullinated peptide antibody (CCP), anti-RA33, anti-keratin
      antibody (AKA), and anti-nuclear antibody (ANA) in RA patients (n = 305) were
      72.13%, 36.39%, 44.92%, and 60.98%, respectively. Results of rheumatoid factor
      (RF) and C-reactive protein (CRP) were 148.29 +/- 391.01 IU/mL and 18.14 +/-
      26.87 mg/L, respectively, which were significantly different from those in
      control group (p < 0.01, t-test). The results indicated that the HLA- DR4 gene
      was clearly associated with susceptibility of RA. Combined detection of related
      auto antibodies might improve diagnosis rate of RA significantly, and the
      positive rate was higher than that for a single antibody.

PMID- 23537299
TI  - AlphaLISA for the determination of median levels of the free beta subunit of
      human chorionic gonadotropin in the serum of pregnant women.
AB  - Measurement of the free beta subunit of human chorionic gonadotropin (free beta
      hCG) in serum is useful for prenatal screening. Concentrations of free beta-hCG
      vary in different races. Conventional assays used for such measurements have
      limitations. We applied the AlphaLISA to measure levels of free beta-hCG in
      maternal serum during 8-20 weeks of gestation in women from southern China. Two
      anti-free beta-hCG antibodies were used: one was coated on AlphaLISA acceptor
      beads and the one was biotinylated. The assay also contained donor beads coated
      with streptavidin. The AlphaLISA assay detection limit was 0.11 ng/mL, and the
      analytical range was 0.11-200 ng/mL. The intra- and interassay coefficients of
      variation were 1.32%-2.50% and 3.44%-5.45%, respectively. The correlation with
      commercial Eu(3+)-labeled free beta-HCG-TRFIA assay was good (y = 1.045x + 1.580,
      r(2) = 0.978). Median levels of free beta-hCG in maternal serum at 8-20 weeks
      gestation were higher in women from southern China compared with those reported
      in women from other countries. The AlphaLISA for free beta-HCG could become the
      assay of choice for applications in clinical diagnostics. The established median
      value of free beta-HCG is helpful in clinical diagnosis specific for southern
      Chinese women.

PMID- 23537300
TI  - Detection of isoprothiolane in food, soil, and water samples by immunosorbent
      assay using avian antibodies.
AB  - A simple competitive immunoassay was developed for the measurement of
      isoprothiolane in rice, soil, and water samples. It employed the avian antibodies
      (IgY) that recognized isoprothiolane as a capture reagent and isoprothiolane
      alkaline phosphatase conjugate as an enzyme label. The assay depended on the
      competitive binding between the anti-isoprothiolane antibody and isoprothiolane
      derived from rice, soil, and water samples for binding sites with immobilized
      isoprothiolane-ovalbumin (OVA) conjugate. The concentration of isoprothiolane in
      the rice, soil, and water samples was quantified by the ability of the pesticide
      present in the samples to inhibit the binding of the enzyme conjugate to the
      antibody and subsequently the color formation in the assay. The assay was
      specific to isoprothiolane with a limit of detection of 2 ng/mL. Mean analytical
      recovery of isoprothiolane in different rice matrices was 87.20%-98.02%, for soil
      samples recovery was 74.24%-111.20%, and water samples recovery was 35.2%-95.73%.
      The precision of the assay was satisfactory. The assay compared favorably with
      gas chromatography (GC) in its ability to accurately measure isoprothiolane in
      the different rice, soil, and water samples.

PMID- 23537301
TI  - apoB-independent enzyme immunoassay for lipoprotein(a) by capture on immobilized
      lectin (jacalin).
AB  - Enzyme immunoassay for lipoprotein(a) [Lp(a)] using antibodies to both apoB and
      apo(a) subunits (a-B assay) is shown to be affected by differential masking of
      apoB by apo(a) and the presence of LDL-Lp(a) adducts. An apoB-independent
      immunoassay by capturing Lp(a) through its O-glycans on microplate-coated lectin
      jacalin and quantitation using peroxidase-labeled anti-apo(a) (J-a assay) is
      described. J-a assay response is linear, more than twice as sensitive as a-B
      assay, and is suppressed only 18 +/- 5% by non-Lp(a) O-glycan-containing proteins
      of serum. Wide variations in IgA did not significantly affect Lp(a) binding to
      jacalin (CV = 6.4%).

PMID- 23537302
TI  - Oligomeric adiponectin forms and their complexes in the blood of healthy donors
      and patients with type 2 diabetes mellitus.
AB  - Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric
      forms, namely low-, medium-, and high-molecular-weight forms. Adn may serve as a
      risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were (1)
      to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric
      forms, (2) to design immunoassays suitable for measuring the Adn forms present in
      human blood, and (3) to investigate the changes in Adn forms that occur in
      patients with T2DM. Gel filtration, fluoroimmunoassays, and Western blotting were
      utilized as major techniques in this study. MAbs recognizing various oligomeric
      forms of Adn were obtained. Complexes between Adn and complement component C1q
      and between the low molecular weight form of Adn and albumin were described in
      human blood. A decrease in the total Adn and Adn-albumin complex levels in the
      blood of patients with T2DM and no difference in the levels of the Adn-C1q
      complex in comparison with healthy volunteers were demonstrated. An Adn94-Adn63
      fluoroimmunoassay was selected as the technique that most accurately measured the
      mass ratio of Adn oligomers in blood samples, and an Adn214-Adn27 assay that
      measured the low-molecular-weight form of Adn only.

PMID- 23537303
TI  - A hypersensitive biotin-avidin-TRFIA for quantitative detection of ANA-Ig(GAM)
      and its clinical application.
AB  - We demonstrate herein a novel time-resolved fluoroimmunoassay (TRFIA) with high
      sensitivity and wide range for quantitative detection of ANA-Ig(GAM) antibodies
      using a biotin-avidin amplification system. The immunoassay was conducted by
      following procedures for a typical sandwich immunoreactions with cell nucleus
      form Hela and the Eu(3+)-labeled biotin combined with biotinylated mouse anti
      human Ig(GAM) served as the solid nuclear antigen for ANA and the tracer,
      respectively. The sensitivity, specificity, and stability of the kit were
      evaluated and comparison with the classical enzyme-linked immunosorbent assay
      (ELISA) kit was also made. The average intra-assay and interassay CVs detected by
      the established ANA-Ig(GAM) biotin-avidin-TRFIA were 4.21% and 6.34%,
      respectively. The lower detection limit was 2.24 U/mL, and the mean recovery rate
      was 100.74%. The good measurable range of the established biotin-avidin-TRFIA was
      within 1.95-64,000 U/mL, while it was only within 32.5-4000 U/mL using an ELISA
      kit. The values determined by the biotin-avidin-TRFIA and ELISA correlated well
      (R2 = 0.989). The positive rate of healthy volunteers and patients with systemic
      lupus erythematosus (SLE), rheumatoid arthritis (RA), primary biliary cirrhosis
      (PBC), Sjogren's syndrome (SS), scleroderma, and mixed connective tissue disease
      (MCTD) was 0, 100%, 18.5%, 100%, 37.9%, 90.9%, and 92%, respectively. We conclude
      that the biotin-avidin-TRFIA we developed gives promise for greater sensitivity
      and accurate detection for ANA-Ig(GAM) in diagnosing and monitoring autoimmune
      disorders.

PMID- 23537304
TI  - Determination of measles hemagglutination inhibiting antibody levels among school
      children in Ibadan, Nigeria.
AB  - Immune status of school children aged from 10-23 years against measles virus was
      determined by the hemagglutination-inhibition (HI) test with a view of assessing
      herd immunity. Blood samples from 500 schoolchildren were collected by finger
      pricking in Ropacco filter papers. Sera were extracted in 1 mL of cold phosphate
      buffered saline and treated with 25% (w/v) kaolin and 50.0% monkey red blood cell
      (RBC) to a final concentration of 1:10. The measles hemagglutinating antigen used
      for the test was prepared from measles vaccine. Results showed that 62 (12.4%)
      were positive for measles HI antibody at a titer of 1:640, and 78 (15.6%) had a
      titer <1:10. There was no significant relationship (P > 0.05) between antibody
      titer and the schools, while a significant relationship (P < 0.05) existed
      between antibody titer and age. Although the majority of the schoolchildren had
      the measles antibody in their sera, titers were, however, beneath the threshold
      of protection in 33.4% of them. The significant association between age of the
      schoolchildren and HI titers showed that those antibodies were waning according
      to age. The study has shown a considerable high level of protection against
      measles among schoolchildren. To prevent future outbreak of measles among these
      schoolchildren, it will be advocated that a second dose of measles vaccine be
      administered.

PMID- 23537305
TI  - Microarray-based component-resolved diagnosis of latex allergy: isolated IgE
      mediated sensitization to latexprofilin Hev b8 may act as confounder.
AB  - Immediate type allergy to latex is still a widespread problem. Latex-allergic
      patients undergoing diagnostic and operative medical procedures are at risk of
      potentially life-threatening reactions. Accurate diagnostic methods are therefore
      crucial. The aim of this retrospective study was to discriminate between
      sensitization and relevant allergy to latex based on an easy and suitable
      diagnostic approach. In 14 patients with clinical symptoms and 27 controls, latex
      skin prick tests (SPT), IgE against latex (CAP) and serological component
      resolved specific latex-allergen determination (Hev b1, b3, b5, b6, b7, b8, b9,
      b10, b11) based on ImmunoCAP ISAC were performed. SPT correlated very well with
      clinically manifest latex-allergy demonstrating a high specificity (95%) (and a
      low sensitivity). However, CAP levels to crude latex could not safely
      discriminate between purely sensitized and latex-allergic patients. The majority
      of patients mono-sensitized to the latex profilin Hev b8 did not suffer from any
      relevant symptoms upon contact with latex. However, in two patients with latex
      allergy diagnosed by elevated specific IgE only sensitized against Hev b8,
      additional sensitization to carbohydrate cross-reactive determinants (CCD) was
      found. In the case of positive serum IgE against latex and negative SPT,
      component-resolved diagnosis including IgE against specific latex-proteins,
      specially Hev b8, and carbohydrate cross-reactive determinants (CCD) is a useful
      tool to discriminate between latex-sensitization and latex-allergy.

PMID- 23537306
TI  - Transition from molecule to solid state: reactivity of supported metal clusters.
AB  - The evolution of the adsorption energy of carbon monoxide (CO) molecules on
      palladium (Pd) clusters as function of Pd particle size from the molecular regime
      (less than ~100 atoms per particle) to the bulk regime has been revealed. This
      adsorption energy is retrieved from the residence time of CO molecules on the Pd
      clusters, measured by a pulsed molecular beam technique, versus temperature.
      Unprecedented accuracy on the determination of the particle size has been
      achieved here by using a regular array of metal clusters exhibiting a size
      dispersion down to the ultimate limit of a Poisson distribution. This allows
      getting rid of the convolution effects that generally occur when considering
      particles grown through other techniques.

PMID- 23537307
TI  - Abstracts of the Thirty-third Annual Meeting of the Surgical Infection Society.
      Las Vegas, Nevada, USA. April 12-15, 2013.

PMID- 23537308
TI  - closo-Hydroborates from liquid ammonia: synthesis and crystal structures of
      [Li(NH3)4]2[B12H12].2NH3, Rb2[B12H12].8NH3, Cs2[B12H12].6NH3 and
      Rb2[B10H10].5NH3.
AB  - Ammonia complexes of hydroborates may be potentially promising materials for
      ammonia storage or indirect hydrogen storage. The title compounds contain 20.04
      52.23 wt % ammonia and 5.94-13.01 wt % hydrogen. They were synthesized in liquid
      ammonia, using (NBu4)2[B12H12] and Li2[B10H10] as starting materials.
      [Li(NH3)4]2[B12H12].2NH3 (1) crystallizes in the monoclinic crystal system (space
      group P2(1)/c, a = 9.183(2) A, b = 8.133(1) A, c = 16.375 A, beta = 110.54(1)
      degrees , V = 1143.97(40) A(3), Z = 2). The compound is a direct precursor of the
      hydrogen storage compound Li2[B12H12].7NH3. Hydroborates of the heavier alkali
      metals were found to crystallize in the orthorhombic crystal system:
      Rb2[B12H12].8NH3 (2) (space group Pnnm, a = 14.4166(6) A, b = 7.8221(3) A, c =
      9.5792(4) A, V = 1080.23(8) A(3), Z = 2), Cs2[B12H12].6NH3 (3) (space group Pbca,
      a = 7.7569(8) A, b = 14.087(2) A, c = 18.075(2) A, V = 1974.99(30) A(3), Z = 4),
      and Rb2[B10H10].5NH3 (4) (space group Pnma, a = 13.9510(7) A, b = 8.675(2) A, c =
      13.966(2) A, V = 1690.2(3) A(3), Z = 4), as determined by single crystal X-ray
      diffraction. The structures are discussed briefly.

PMID- 23537309
TI  - Strategies to sustain and scale up youth friendly health services in the Republic
      of Moldova.
AB  - As part of a multifaceted effort to respond to the needs of young people more
      effectively, the Ministry of Health of the Republic of Moldova established pilot
      Youth Friendly Health Centres (YFHC) in 2001. In 2005, after 12 YFHC were set up
      and implemented, the MOH identified that while they were serving a useful
      function, four problems remained needed to be addressed - the lack of an
      operational definition of the term youth friendly health services, the lack of
      objective data on the added value of the existing YFHC, the low coverage of the
      existing YFHC and the almost complete reliance on donor agencies for funding the
      effort. The MOH addressed each of these problems systematically. While challenges
      still exist, the MOH has taken important steps to ensure that all young people in
      the country can obtain the health services they need.

PMID- 23537310
TI  - Silica nanoparticles as a tool for fluorescence collection efficiency
      enhancement.
AB  - In this work we demonstrate enhancement of the fluorescence collection efficiency
      for chlorophyll-containing photosynthetic complexes deposited on SiO2 spherical
      nanoparticles. Microscopic images of fluorescence emission reveal ring-like
      emission patterns associated with chlorophyll-containing complexes coupled to
      electromagnetic modes within the silica nanoparticles. The interaction leaves no
      effect upon the emission spectra of the complexes, and the transient behavior of
      the fluorescence also remains unchanged, which indicates no influence of the
      silica nanoparticles on the radiative properties of the fluorophores. We
      interpret this enhancement as a result of efficient scattering of electromagnetic
      field by the dielectric nanoparticles that increases collection efficiency of
      fluorescence emission.

PMID- 23537311
TI  - The impact of retrograde intrarenal surgery for asymptomatic renal stones in
      patients undergoing ureteroscopy for a symptomatic ureteral stone.
AB  - BACKGROUND AND PURPOSE: In the era of rigid ureteroscopy (URS) for ureteral
      stones, asymptomatic renal stones were often left in place. With the advent of
      flexible URS, however, the treatment of such renal stones became an attractive
      option. Data are scarce regarding the impact of retrograde intrarenal surgery
      (RIRS) performed at the time of URS for a symptomatic ureteral stone in
      comparison with ureteral stone removal alone. The purpose of the study was to
      compare the outcomes of URS combined with RIRS with URS alone. PATIENTS AND
      METHODS: A comparison between patients who underwent URS and RIRS (group A, n=47)
      and a matched control group of patients undergoing URS alone (group B, n=47) was
      performed. Matching was based on ureteral stone size and location, and
      preprocedural Double-J stent placement. RESULTS: The median size of the largest
      ureteral stone in both groups was 8 mm with a mean total stone burden of 52.9
      mm(2) (28.9) and 47 mm(2) (21.1) in groups A and B, respectively. Median renal
      stone size was 9 mm with a mean total stone burden of 84.1 mm(2) (40.3). Mean
      surgery time in groups A and B was 68 minutes (19.61) and 39 minutes (15.96),
      respectively (P<0.001). Median hospital stay was 1 day for both groups. The
      success rate for ureteral stone removal was 98% and 100% in groups A and B,
      respectively. Success rate for RIRS was 85% (40/47 cases). Hospitalization length
      and complications, mainly postoperative fever, did not differ significantly
      between the groups. CONCLUSIONS: Managing asymptomatic renal stones at the time
      of URS for symptomatic ureteral stones significantly prolongs surgery duration
      but does not lengthen hospital stay, increase complications, or lower success
      rates. This combined approach reduces the need for future procedures and is
      probably more cost effective.

PMID- 23537312
TI  - Dutch postgraduate GP selection procedure; reliability of interview assessments.
AB  - BACKGROUND: Semi- structured interviews are the core of the Dutch selection
      procedure for postgraduate general practice (GP) training. A staff member,
      trainer and trainee independently assess personal qualities. Aiming to improve
      the selection procedure we were interested in the reliability aspects of these
      interviews. We investigated the inter-rater reliability of the interview for
      groups of two or three assessors and the degree to which candidates'
      characteristics and qualities assessed during interviews explained admission into
      GP training, controlled for differences between those who apply for the first
      versus the second or third application. METHODS: An observational study was
      conducted of all candidates who entered the Utrecht selection procedure between
      April 2008 and 2010. Candidates' characteristics and qualities were collected.
      Inter-rater reliability of different compositions of the interview group per
      quality was estimated. Factors associated with admission into GP training were
      assessed. RESULTS: The study population included 394 candidates. Twenty-six
      candidates were rejected based on their application letter (4.4%). Three
      candidates who applied more than 3 times were excluded. Ultimately, 206 of the
      365 candidates were admitted to the GP training (56,4%). The inter-rater
      reliability was satisfactory (ICC: 0.78 - 0 .84). Reduction from three to two
      assessors slightly reduces the ICC. The candidates' qualities independently
      explained admission to GP training, whereas individual characteristics did not.
      These results did not differ for candidates who applied for the first time versus
      candidates applying for the second or third time. CONCLUSION: Selection
      interviews with two assessors yielded a satisfactory level of reliability.
      Individual characteristics were not associated with admission, whereas scores
      related to candidate qualities did show such an association. The results of those
      applying for the second or third time were similar.

PMID- 23537314
TI  - Performance on Standard Indexes of Effort Among Patients With Dementia.
AB  - Assessment of response validity is an integral part of neuropsychological
      practice. Although many studies have demonstrated the efficacy of stand alone and
      embedded effort measures in a variety of medical and compensation-seeking
      contexts, much less is known about the robustness of these measures in elderly
      populations, particularly in patients with dementia. Although older adults may be
      viewed as less likely to intentionally feign symptoms for an external gain, there
      are a variety of other factors that could result in suboptimal effort, including
      fatigue, lack of interest or cooperation in the testing process, or failure to
      fully appreciate the implications of the assessment on treatment care and
      outcome. The current study examined the clinical utility of several stand alone
      and embedded effort measures including the Repeatable Battery for the Assessment
      of Neuropsychological Status Effort Index, Trail-Making Test Ratio, Rey 15-Item
      Test, and the Test of Memory Malingering in a sample of patients with dementia.
      Results found that the majority of effort indexes demonstrated unacceptably high
      false-positive error rates with specificity levels as high as 83%. These findings
      demonstrate the need for caution in interpreting effort measure performance in
      dementia samples due to the fact that despite their best effort, many patients
      with dementia fail effort measures and are at risk for being misclassified.

PMID- 23537313
TI  - Randomised phase 3 open-label trial of first-line treatment with gemcitabine in
      association with docetaxel or paclitaxel in women with metastatic breast cancer:
      a comparison of different schedules and treatments.
AB  - BACKGROUND: This open-label study compared docetaxel/gemcitabine vs.
      paclitaxel/gemcitabine and a weekly (W) vs. 3-weekly (3 W) schedule in metastatic
      breast cancer (MBC). METHODS: Patients relapsed after adjuvant/neoadjuvant
      anthracycline-containing chemotherapy were randomized to: A) gemcitabine 1000
      mg/m2 Day 1,8 + docetaxel 75 mg/m2 Day 1 q3W; B) gemcitabine 1250 mg/m2 Day 1,8 +
      paclitaxel 175 mg/m2 Day 1 q3W; C) gemcitabine 800 mg/m2 Day 1,8,15 + docetaxel
      30 mg/m2 Day 1,8,15 q4W; D) gemcitabine 800 mg/m2 Day 1,15 + paclitaxel 80 mg/m2
      Day 1,8,15 q4W. Primary endpoint was time-to-progression (TTP). Secondary
      endpoints were overall survival (OS) and overall response rate (ORR). RESULTS:
      Interim analysis led to accrual interruption (241 patients enrolled of 360
      planned). Median TTP (months) was 8.33 (95% CI: 6.19-10.16) with W and 7.51 (95%
      CI: 5.93-8.33) with 3 W (p=0.319). No differences were observed in median TTP
      between docetaxel and paclitaxel, with 85.6% and 87.0% of patients progressing,
      respectively. OS did not differ between regimens/schedules. ORR was comparable
      between regimens (HR: 0.882; 95% CI: 0.523-1.488; p=0.639), while it was
      significantly higher in W than in the 3 W (HR: 0.504; 95% CI: 0.299-0.850;
      p=0.010) schedule. Grade 3/4 toxicities occurred in 69.2% and 71.9% of patients
      on docetaxel and paclitaxel, and in 65.8% and 75.2% in W and 3 W. CONCLUSIONS:
      Both treatment regimens showed similar TTP. W might be associated with a better
      tumour response compared with 3 W. TRIAL REGISTRATION: Clinicaltrial.gov ID
      NCT00236899.

PMID- 23537315
TI  - Hydrocarbon-soluble nanocatalysts with no bulk phase: coplanar, two-coordinate
      arrays of the base metals.
AB  - A structurally unique class of hydrocarbon-soluble, ancillary-ligand-free,
      tetrametallic Co(I) and Ni(I) clusters is reported. The highly unsaturated
      complexes are supported by simple, sterically bulky phosphoranimide ligands, one
      per metal. The electron-rich nitrogen centers are strongly bridging but
      sterically limited to bimetallic interactions. The hydrocarbon-soluble clusters
      consist of four coplanar metal centers, mutually bridged by single nitrogen
      atoms. Each metal center is monovalent, rigorously linear, and two-coordinate.
      The clusters are in essence two-dimensional atomic-scale "molecular squares," a
      structural motif adapted from supramolecular chemistry. Both clusters exhibit
      high solution-phase magnetic susceptibility at room temperature, suggesting the
      potential for applications in molecular electronics. Designed to be catalyst
      precursors, both clusters exhibit high activity for catalytic hydrogenation of
      unsaturated hydrocarbons at low pressure and temperature.

PMID- 23537316
TI  - Is pycnogenol a double-edged sword? Cataractogenic in vitro, but reduces cataract
      risk in diabetic rats.
AB  - PURPOSE: Pycnogenol was used (a) to study its antioxidant activity, (b) to study
      its effects on lens integrity in organ culture and (c) in vivo to determine
      whether it could reduce the damage in model diabetic cataract. METHODS: For (a)
      our luminescent antioxidant assay was used, (b) lenses were incubated in medium
      199, with 55.6 mM glucose. Lenses were stained with 0.014 mM rhodamine 123 for 15
      min to stain mitochondria, immobilized in 1% agarose in M199, and the equatorial
      region examined by a Zeiss confocal microscope. For (c) cataract grades of
      streptozotocin diabetic rats fed 1% pycnogenol were followed for 12 weeks.
      RESULTS: (a) Pycnogenol in vitro was an antioxidant when challenged with
      peroxide. (b) In vitro, when [570 mg/L] pycnogenol in dimethyl sulfoxide (DMSO)
      was used, lenses turned opaque after 3 d of incubation, in both pycnogenol
      controls and glucose + pycnogenol. Normal controls (DMSO, n = 4) and controls (n
      = 4) remained clear after 8 d of incubation. After 3 d of incubation with
      pycnogenol, cumulative protein leakage was greater than 0.28 mg/mL versus 8 d
      controls (0.018 mg/mL). Similar damage occurred at pycnogenol concentrations as
      low as 20 mg/L. The 20 mg/L pycnogenol control showed mitochondrial death, and
      calcium concentration in the lens equatorial differentiating fiber cells
      increased. (c) In vivo feeding pycnogenol resulted in similar growth and body
      condition for diabetic rats, and lower cataract grades at 9 and 11 weeks: final
      serum glucose levels were not significantly different, but glycohemoglobin A1
      levels were significantly lower (83.9% of normal, p < 0.05) in pycnogenol-fed
      diabetic rats. CONCLUSIONS: Although it appears that pycnogenol has a potential
      toxic effect on incubated lenses, it appears in vivo to have a marginal
      protective effect, and also significantly reduces glycation of proteins.
      Supported by Cognis US (formerly Henkel Chemical Co.) and Horphag Research.

PMID- 23537317
TI  - Bacteria and tumours: causative agents or opportunistic inhabitants?
AB  - Associations between different bacteria and various tumours have been reported in
      patients for decades. Studies involving characterisation of bacteria within
      tumour tissues have traditionally been in the context of tumourigenesis as a
      result of bacterial presence within healthy tissues, and in general, dogma holds
      that such bacteria are causative agents of malignancy (directly or indirectly).
      While evidence suggests that this may be the case for certain tumour types and
      bacterial species, it is plausible that in many cases, clinical observations of
      bacteria within tumours arise from spontaneous infection of established tumours.
      Indeed, growth of bacteria specifically within tumours following deliberate
      systemic administration has been demonstrated for numerous bacterial species at
      preclinical and clinical levels. We present the available data on links between
      bacteria and tumours, and propose that besides the few instances in which
      pathogens are playing a pathogenic role in cancer, in many instances, the
      prevalent relationship between solid tumours and bacteria is opportunistic rather
      than causative, and discuss opportunities for exploiting tumour-specific
      bacterial growth for cancer treatment.

PMID- 23537318
TI  - Bronsted acid cocatalysts in photocatalytic radical addition of alpha-amino C-H
      bonds across Michael acceptors.
AB  - In marked contrast to the variety of strategies available for oxidation and
      nucleophilic functionalization of methylene groups adjacent to amines, relatively
      few approaches for modification of this position with electrophilic reaction
      partners have been reported. In the course of an investigation of the reactions
      of photogenerated alpha-amino radicals with electrophiles, we made the surprising
      observation that the efficiency of radical photoredox functionalization of N-aryl
      tetrahydroisoquinolines is dramatically increased in the presence of a Bronsted
      acid cocatalyst. Optimized conditions provide high yields and efficient
      conversion to radical addition products for a range of structurally modified
      tetrahydroisoquinolines and enones using convenient household light sources and
      commercially available Ru(bpy)3Cl2 as a photocatalyst. Our investigations into
      the origins of this unexpected additive effect have demonstrated that the carbon
      carbon bond-forming step is accelerated by TFA and is a rare example of Bronsted
      acid catalysis in radical addition reactions. Moreover, a significant conclusion
      arising from these studies is the finding that product formation is dominated by
      radical chain processes and not by photocatalyst turnover. Together, these
      findings have important implications for the future design and mechanistic
      evaluation of photocatalytic radical processses.

PMID- 23537319
TI  - Dietary patterns and metabolic syndrome in a Japanese working population.
AB  - BACKGROUND: Metabolic syndrome has become a major public health concern, but the
      role of diet in the etiology of this syndrome is not well understood. This study
      investigated the association between major dietary patterns and prevalence of
      metabolic syndrome in a Japanese working population. METHODS: This cross
      sectional study was conducted among 460 municipal employees (284 men and 176
      women), aged 21-67 years, who participated in a health survey at the time of
      periodic checkup. Dietary patterns were derived by using the principal component
      analysis of the consumption of 52 food and beverage items, which were assessed by
      a validated brief diet history questionnaire. Metabolic syndrome was defined
      according to the modified NCEP-ATP III criteria. Logistic regression was used to
      examine the association between dietary patterns and metabolic syndrome with
      adjustment of potential confounding variables. RESULTS: Three dietary patterns
      were identified. Westernized breakfast pattern characterized by high intakes of
      bread, confectionaries, and milk and yogurt but low intakes of rice and alcoholic
      beverages was inversely associated with prevalence of metabolic syndrome and high
      blood pressure (P for trend = 0.02 and 0.049, respectively). Animal food pattern
      characterized by high intakes of fish and shellfish, meat, processed meat,
      mayonnaise, and egg was not associated with prevalence of metabolic syndrome, but
      was positively associated with high blood glucose (P for trend = 0.03). Healthy
      Japanese dietary pattern characterized by vegetables and fruits, soy products,
      mushrooms, and green tea was not appreciably associated with prevalence of
      metabolic syndrome or its components. CONCLUSIONS: The results suggest that
      westernized breakfast pattern may confer some protection against metabolic
      syndrome in Japanese. The causality of these associations needs to be confirmed.

PMID- 23537320
TI  - Delayed ventricular septal rupture complicating acute inferior wall myocardial
      infarction.
AB  - BACKGROUND: Ventricular septal rupture is a potentially fatal complication of
      acute myocardial infarction. Its incidence has declined with modern reperfusion
      therapy. In the era of percutaneous coronary interventions, it occurs a median of
      18-24 hours after myocardial infarction and is most commonly associated with
      anterior myocardial infarction. We present a case of delayed ventricular septal
      rupture complicating acute inferior wall myocardial infarction. CASE
      PRESENTATION: A 53-year-old Caucasian male presented with epigastric pain for
      three days and electrocardiographic evidence for an acute inferior wall
      myocardial infarction. Coronary angiography revealed a total occlusion of the
      proximal right coronary artery. Reperfusion was achieved by balloon angioplasty
      followed by placement of a bare metal stent. On hospital day six, the patient
      developed acute respiratory distress, a new loud pansystolic murmur, and
      hemodynamic instability. Echocardiography revealed the presence of a large defect
      in the inferobasal interventricular septum with significant left-to-right shunt
      consistent with ventricular septal rupture. The patient underwent emergent
      surgical repair with a bovine pericardial patch. CONCLUSION: Ventricular septal
      rupture after myocardial infarction should be suspected in the presence of new
      physical findings and hemodynamic compromise regardless of revascularization
      therapy.

PMID- 23537321
TI  - Spray drying method for large-scale and high-performance silicon negative
      electrodes in Li-ion batteries.
AB  - Nanostructured silicon electrodes have shown great potential as lithium ion
      battery anodes because they can address capacity fading mechanisms originating
      from large volume changes of silicon alloys while delivering extraordinarily
      large gravimetric capacities. Nonetheless, synthesis of well-defined silicon
      nanostructures in an industrially adaptable scale still remains as a challenge.
      Herein, we adopt an industrially established spray drying process to enable
      scalable synthesis of silicon-carbon composite particles in which silicon
      nanoparticles are embedded in porous carbon particles. The void space existing in
      the porous carbon accommodates the volume expansion of silicon and thus addresses
      the chronic fading mechanisms of silicon anodes. The composite electrodes exhibit
      excellent electrochemical performance, such as 1956 mAh/g at 0.05C rate and 91%
      capacity retention after 150 cycles. Moreover, the spray drying method requires
      only 2 s for the formation of each particle and allows a production capability of
      ~10 g/h even with an ultrasonic-based lab-scale equipment. This investigation
      suggests that established industrial processes could be adaptable to the
      production of battery active materials that require sophisticated nanostructures
      as well as large quantity syntheses.

PMID- 23537322
TI  - Solid-state structure and calculated electronic structure, formation energy,
      chemical bonding, and optical properties of Zn4O(FMA)3 and its heavier congener
      Cd4O(FMA)3.
AB  - The equilibrium solid-state structure of the experimentally synthesized but
      incompletely characterized Zn4O(FMA)3 is revised with the help of density
      functional theory computational methods. The electronic structure, formation
      energy, chemical bonding, and optical properties of Zn4O(FMA)3 and its heavier
      congener Cd4O(FMA)3 have been systematically investigated. The calculated bulk
      moduli for Zn4O(FMA)3 and Cd4O(FMA)3 are similarly small (and slightly smaller
      than the previously reported values for MOF-5), indicative of relatively soft
      materials. Their estimated band-gap values are ca. 3.2 eV (somewhat lower than
      that of MOF-5, 3.4-3.5 eV), indicating semiconducting character. The optical
      properties including dielectric function epsilon(omega), refractive index
      n(omega), absorption coefficient alpha(omega), optical conductivity sigma(omega),
      reflectivity R(omega), and electron energy-loss spectrum L(omega) of M4O(FMA)3 (M
      = Zn, Cd) were systematically studied. Analysis of chemical bonding reveals that
      the M-O bonds are largely ionic, with an increase in ionicity from Zn to Cd. The
      total energy calculations establish that compounds M4O(FMA)3 have large negative
      formation energies, ca. -80 and -70 kJ.mol(-1) for Zn and Cd, respectively.
      Whereas Zn4O(FMA)3 has already been synthesized, the results suggest that the
      heavier congener Cd4O(FMA)3 might be experimentally accessible.

PMID- 23537324
TI  - Bacterial Obg proteins: GTPases at the nexus of protein and DNA synthesis.
AB  - Obg proteins (also known as ObgE, YhbZ and CgtA) are conserved P-loop GTPases,
      essential for growth in bacteria. Like other GTPases, Obg proteins cycle between
      a GTP-bound ON and a GDP-bound OFF state, thereby controlling cellular processes.
      Interestingly, the in vitro biochemical properties of Obg proteins suggest that
      they act as sensors for the cellular GDP/GTP pools and adjust their activity
      according to the cellular energy status. Obg proteins have been attributed a host
      of cellular functions, including roles in essential cellular processes (DNA
      replication, ribosome maturation) and roles in different stress adaptation
      pathways (stringent response, sporulation, general stress response). This review
      summarizes the current knowledge on Obg activity and function. Furthermore, we
      present a model that integrates the different functions of Obg by assigning it a
      fundamental role in cellular physiology, at the hub of protein and DNA synthesis.
      In particular, we believe that Obg proteins might provide a connection between
      different global pathways in order to fine-tune cellular processes in response to
      a given energy status.

PMID- 23537323
TI  - Neuroimaging studies of alexithymia: physical, affective, and social
      perspectives.
AB  - Alexithymia refers to difficulty in identifying and expressing one's emotions,
      and it is related to disturbed emotional regulation. It was originally proposed
      as a personality trait that plays a central role in psychosomatic diseases. This
      review of neuroimaging studies on alexithymia suggests that alexithymia is
      associated with reduced neural responses to emotional stimuli from the external
      environment, as well as with reduced activity during imagery, in the limbic and
      paralimbic areas (i.e., amygdala, insula, anterior/posterior cingulate cortex).
      In contrast, alexithymia is also known to be associated with enhanced neural
      activity in somatosensory and sensorimotor regions, including the insula.
      Moreover, neural activity in the medial, prefrontal, and insula cortex was
      lowered when people with alexithymia were involved in social tasks. Because most
      neuroimaging studies have been based on sampling by self-reported questionnaires,
      the contrasted features of neural activities in response to internal and external
      emotional stimuli need to be elucidated. The social and emotional responses of
      people with alexithymia are discussed and recommendations for future research are
      presented.

PMID- 23537325
TI  - The cellulolytic system of Thermobifida fusca.
AB  - The process of bioethanol production from biomass comprises pretreatments and
      enzyme-mediated hydrolysis to convert lignocellulose into fermentable sugars.
      Because of the recalcitrant character of cellulose, the enzymatic hydrolysis is
      considered the major challenge in this process to be economically competitive.
      These technical difficulties highlight the need for the discovery of new enzymes
      to optimize and lower the cost of current technologies. Microorganisms have
      developed efficient systems for cellulose degradation. Among cellulolytic
      microbes, Thermobifida fusca possesses great physiological and cellulolytic
      characteristics (thermostability, high activity and tolerance to a broad pH
      range) making it an interesting organism to be studied from an applied
      perspective. In this review we describe the main enzymes/proteins produced by
      T.fusca (cellulases, xylanases, mannanase, manosidase, CBM33 and CelR), the
      effect of substrate on T. fusca proteome, enzyme improvement approaches,
      synergism between enzymes/proteins and artificial cellulosomes.

PMID- 23537326
TI  - Airway distensibility by HRCT in asthmatics and COPD with comparable airway
      obstruction.
AB  - INTRODUCTION: Decreased airway distensibility (AD) in response to deep
      inspirations, as assessed by HRCT, has been associated with the severity of
      asthma and COPD. AIMS: The current study was designed to compare the magnitude of
      AD by HRCT in individuals with asthma and COPD with comparable degrees of
      bronchial obstruction, and to explore factors that may influence it. RESULTS: We
      enrolled a total of 12 asthmatics (M/F:7/5) and 8 COPD (7/1) with comparable
      degree of bronchial obstruction (FEV1% predicted mean +/- SEM: 69.1 +/- 5.2% and
      61.2 +/- 5.0%, respectively; p = 0.31). Each subject underwent chest HRCT at FRC
      and at TLC. A total of 701 airways (range 20 to 38 airway per subject; 2.0 to
      23.1 mm in diameter) were analyzed. AD did not differ between asthmatics and COPD
      (mean +/- SEM: 14 +/- 3.5% and 17 +/- 4.3%, respectively; p = 0.58). In
      asthmatics, AD was significantly associated with FEV1% predicted (r(2) = 0.45, p
      = 0.018). We found a significant correlation between the change in lung volume
      and the change in AD by HRCT (r(2) = 0.64, p = 0.002). In COPD, we found
      significant correlations between AD and the RV% predicted (r(2) = 0.51, p =
      0.046) and the RV/TLC (r(2) = 0.68, p = 0.01). CONCLUSIONS: AD was primarily
      affected by the dynamic ability to change lung volumes in asthmatics, and by
      static lung volumes in COPD.

PMID- 23537327
TI  - Minimal improvement of nurses' motivational interviewing skills in routine
      diabetes care one year after training: a cluster randomized trial.
AB  - BACKGROUND: The effectiveness of nurse-led motivational interviewing (MI) in
      routine diabetes care in general practice is inconclusive. Knowledge about the
      extent to which nurses apply MI skills and the factors that affect the usage can
      help to understand the black box of this intervention. The current study compared
      MI skills of trained versus non-trained general practice nurses in diabetes
      consultations. The nurses participated in a cluster randomized trial in which a
      comprehensive program (including MI training) was tested on improving clinical
      parameters, lifestyle, patients' readiness to change lifestyle, and quality of
      life. METHODS: Fifty-eight general practices were randomly assigned to usual care
      (35 nurses) or the intervention (30 nurses). The ratings of applying 24 MI skills
      (primary outcome) were based on five consultation recordings per nurse at
      baseline and 14 months later. Two judges evaluated independently the MI skills
      and the consultation characteristics time, amount of nurse communication, amount
      of lifestyle discussion and patients' readiness to change. The effect of the
      training on the MI skills was analysed with a multilevel linear regression by
      comparing baseline and the one-year follow-up between the interventions with
      usual care group. The overall effect of the consultation characteristics on the
      MI skills was studied in a multilevel regression analyses. RESULTS: At one year
      follow up, it was demonstrated that the nurses improved on 2 of the 24 MI skills,
      namely, "inviting the patient to talk about behaviour change" (mean
      difference=0.39, p=0.009), and "assessing patient's confidence in changing their
      lifestyle" (mean difference=0.28, p=0.037). Consultation time and the amount of
      lifestyle discussion as well as the patients' readiness to change health
      behaviour was associated positively with applying MI skills. CONCLUSIONS: The
      maintenance of the MI skills one year after the training program was minimal. The
      question is whether the success of MI to change unhealthy behaviour must be
      doubted, whether the technique is less suitable for patients with a complex
      chronic disease, such as diabetes mellitus, or that nurses have problems with the
      acquisition and maintenance of MI skills in daily practice. Overall, performing
      MI skills during consultation increases, if there is more time, more lifestyle
      discussion, and the patients show more readiness to change. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN68707773.

PMID- 23537328
TI  - GlgS, described previously as a glycogen synthesis control protein, negatively
      regulates motility and biofilm formation in Escherichia coli.
AB  - Escherichia coli glycogen metabolism involves the regulation of glgBXCAP operon
      expression and allosteric control of the GlgC [ADPG (ADP-glucose)
      pyrophosphorylase]-mediated catalysis of ATP and G1P (glucose-1-phosphate) to
      ADPG linked to glycogen biosynthesis. E. coli glycogen metabolism is also
      affected by glgS. Though the precise function of the protein it encodes is
      unknown, its deficiency causes both reduced glycogen content and enhanced levels
      of the GlgC-negative allosteric regulator AMP. The transcriptomic analyses
      carried out in the present study revealed that, compared with their isogenic
      BW25113 wild-type strain, glgS-null (DeltaglgS) mutants have increased expression
      of the operons involved in the synthesis of type 1 fimbriae adhesins, flagella
      and nucleotides. In agreement, DeltaglgS cells were hyperflagellated and
      hyperfimbriated, and displayed elevated swarming motility; these phenotypes all
      reverted to the wild-type by ectopic glgS expression. Also, DeltaglgS cells
      accumulated high colanic acid content and displayed increased ability to form
      biofilms on polystyrene surfaces. F-driven conjugation based on large-scale
      interaction studies of glgS with all the non-essential genes of E. coli showed
      that deletion of purine biosynthesis genes complement the glycogen-deficient,
      high motility and high biofilm content phenotypes of DeltaglgS cells. Overall the
      results of the present study indicate that glycogen deficiency in DeltaglgS cells
      can be ascribed to high flagellar propulsion and high exopolysaccharide and
      purine nucleotides biosynthetic activities competing with GlgC for the same ATP
      and G1P pools. Supporting this proposal, glycogen-less DeltaglgC cells displayed
      an elevated swarming motility, and accumulated high levels of colanic acid and
      biofilm. Furthermore, glgC overexpression reverted the glycogen-deficient, high
      swarming motility, high colanic acid and high biofilm content phenotypes of
      DeltaglgS cells to the wild-type. As on the basis of the present study GlgS has
      emerged as a major determinant of E. coli surface composition and because its
      effect on glycogen metabolism appears to be only indirect, we propose to rename
      it as ScoR (surface composition regulator).

PMID- 23537329
TI  - The impact of diurnal variation on induced sputum cell counts in healthy adults.
AB  - BACKGROUND: Induced sputum cell counts are a non-invasive, reliable method for
      evaluating the presence, type, and degree of inflammation in the airways of the
      lungs. Current reference values for induced sputum cell counts in healthy adults
      do not account for the effects of circadian rhythm, including diurnal variation.
      The objective of this study was to describe the diurnal variation in induced
      sputum cell counts, compared between early morning and late afternoon, in healthy
      adult individuals. METHODS: 100 healthy adult subjects with no history of lung
      disease and normal bronchial reactivity proceeded with induced sputum testing at
      7 am and 4 pm on different days. The order of testing was randomized. The
      cytotechnologist preparing and performing the cell counts was blinded to the
      sample collection time and subject characteristics. RESULTS: 65 subjects were
      included in the final analyses. There was no significant change in the total and
      differential sputum cell counts between the 7 am and 4 pm collections. There was
      good inter-observer agreement with respect to differential sputum cell count
      interpretation. CONCLUSIONS: This is the largest study to assess the variation in
      induced sputum cell counts in healthy adult subjects at different times of the
      day. We found no significant change in total and differential sputum cell counts
      between the 7 am and 4 pm collection time points. This is in contrast to studies
      in asthmatics that demonstrated a circadian variation in sputum cell counts and
      other markers of inflammation, suggesting that fluctuations in airway
      inflammatory cells during the day are a disease-specific effect.

PMID- 23537330
TI  - Patient self-appraisal of change and minimal clinically important difference on
      the European organization for the research and treatment of cancer quality of
      life questionnaire core 30 before and during cancer therapy.
AB  - BACKGROUND: Clinical interpretation of health related quality of life (HRQOL)
      scores is challenging. The purpose of this analysis was to interpret score
      changes and identify minimal clinically important differences (MCID) on the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire-Core 30 (QLQ-C30) before (T1) and during (T2) cancer treatment.
      METHODS: Patients (N = 627) in stem cell transplant (SCT) and medical (MED) or
      radiation (RAD) oncology at two comprehensive cancer centers, enrolled in the
      Electronic Self-Report Assessment-Cancer study and completed the QLQ-C30 at T1
      and T2. Perceived changes in five QOL domains, physical (PF), emotional (EF),
      social (SF), cognitive functioning (CF) and global quality of life (QOL), were
      reported using the Subject Significance Questionnaire (SSQ) at T2. Anchored on
      SSQ ratings indicating "improvement", "the same", or "deterioration", means and
      effect sizes were calculated for QLQ-C30 score changes. MCID was calculated as
      the mean difference in QLQ-C30 score changes reflecting one category change on
      SSQ rating, using a two-piece linear regression model. RESULTS: A majority of SCT
      patients (54%) perceived deteriorating global HRQOL versus improvement (17%),
      while approximately equal proportions of MED/RAD patients perceived improvement
      (25%) and deterioration (26%). Global QOL decreased 14.2 (SCT) and 2.0 (MED/RAD)
      units, respectively, among patients reporting "the same" in the SSQ. The MCID
      ranged 5.7-11.4 (SCT) and 7.2-11.8 (MED/RAD) units among patients reporting
      deteriorated HRQOL; ranged 2.7-3.4 units among MED/RAD patients reporting
      improvement. Excepting for the global QOL (MCID =6.9), no meaningful MCID was
      identified among SCT patients reporting improvement. CONCLUSIONS: Cancer
      treatment has greater impact on HRQOL among SCT patients than MED/RAD patients.
      The MCID for QLQ-C30 score change differed across domains, and differed for
      perceived improvement and deterioration, suggesting different standards for self
      evaluating changes in HRQOL during cancer treatment. Specifically, clinical
      attention can be focused on patients who report at least a 6 point decrease, and
      for patients who report at least a 3 point increase on QLQ-C30 domains. TRIAL
      REGISTRATION: The trial was registered with ClinicalTrials.gov: NCT00852852.

PMID- 23537331
TI  - Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change
      induced by 2,4,6-trinitrobenzene sulfonic acid.
AB  - BACKGROUND: Visceral pain is common symptom involved in many gastrointestinal
      disorders such as inflammatory bowel disease. The underlying molecular mechanisms
      remain elusive. We investigated the molecular mechanisms and the role for voltage
      gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6
      trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory
      hypersensitivity. RESULTS: Using Agilent cDNA arrays, we found 172 genes changed
      significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these
      changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR
      and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The
      whole cell patch clamp recording of acutely dissociated colonic specific DRG
      neurons showed that the peak IBa density was significantly increased in colonic
      neurons of TNBS treated rats compared with control rats (-127.82 +/- 20.82 pA/pF
      Vs -91.67 +/- 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type
      of calcium currents with the corresponding selective channel blockers, we found
      that L-type (-38.56 +/- 3.97 pA/pF Vs -25.75 +/- 3.35 pA/pF, n = 9, * P < 0.05)
      and R-type (-13.31 +/- 1.36 pA/pF Vs -8.60 +/- 1.25 pA/pF, n = 9, * P < 0.05)
      calcium current density were significantly increased in colonic DRG neurons of
      TNBS treated rats compared with control rats. In addition, pharmacological
      blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with
      intrathecal injection attenuates visceral pain in TNBS induced inflammatory
      visceral hypersensitivity. CONCLUSION: Cav1.2 and Cav2.3 in colonic primary
      sensory neurons play an important role in visceral inflammatory hyperalgesia,
      which maybe the potential therapeutic targets.

PMID- 23537333
TI  - High-reproducibility, flexible conductive patterns fabricated with silver
      nanowire by drop or fit-to-flow method.
AB  - An unusual strategy was designed to fabricate conductive patterns with high
      reproducibility for flexible electronics by drop or fit-to-flow method. Silver
      nanowire (SNW) ink with surface tension of 36.9 mN/m and viscosity of 13.8 mPa s
      at 20 degrees C was prepared and characterized using a field emission
      transmission electron microscope, X-ray diffractometer, thermogravimetric
      analyzer, scanning electron microscope, and four-point probe.
      Polydimethylsiloxane (PDMS) pattern as template was fabricated by spin coating
      (500 rpm), baking at 80 degrees C for 3 h, and laser cutting. The prepared SNW
      ink can flow along the trench of the PDMS pattern spontaneously, especially after
      plasma treatment with oxygen, and show a low resistivity of 12.9 MUOmega cm after
      sintering at 125 degrees C for 30 min. In addition, an antenna pattern was also
      prepared to prove the feasibility of the approach.

PMID- 23537332
TI  - Impact of telemonitoring home care patients with heart failure or chronic lung
      disease from primary care on healthcare resource use (the TELBIL study randomised
      controlled trial).
AB  - BACKGROUND: There is growing evidence that home telemonitoring can be
      advantageous in societies with increasing prevalence of chronic diseases.The main
      objective of this study is to evaluate the effect of a primary care-based
      telemonitoring intervention on the number and length of hospital admissions.
      METHODS: A randomised controlled trial was carried out across 20 health centres
      in Bilbao (Basque Country, Spain) to assess the impact of home telemonitoring on
      in-home chronic patients compared with standard care. The study lasted for one
      year. Fifty-eight in-home patients, diagnosed with heart failure (HF) and/or
      chronic lung disease (CLD), aged 14 or above and with two or more hospital
      admissions in the previous year were recruited. The intervention consisted of
      daily patient self-measurements of respiratory-rate, heart-rate, blood pressure,
      oxygen saturation, weight, body temperature and the completion of a health status
      questionnaire using PDAs. Alerts were generated when pre-established thresholds
      were crossed. The control group (CG) received usual care. The primary outcome
      measure was the number of hospital admissions that occurred at 12 months post
      randomisation. The impact of telemonitoring on the length of hospital stay, use
      of other healthcare resources and mortality was also explored. RESULTS: The
      intervention group (IG) included 28 patients and the CG 30. Patient baseline
      characteristics were similar in both groups. Of the 21 intervention patients
      followed-up for a year, 12 had some admissions (57.1%), compared to 19 of 22
      controls (86.4%), being the difference statistically significant (p = 0.033, RR
      0.66; 95%CI 0.44 to 0.99). The mean hospital stay was overall 9 days (SD 4.3) in
      the IG versus 10.7 (SD 11.2) among controls, and for cause-specific admissions 9
      (SD 4.5) vs. 11.2 (SD 11.8) days, both without statistical significance (p =
      0.891 and 0.927, respectively). Four patients need to be telemonitored for a year
      to prevent one admission (NNT). There were more telephone contacts in the IG than
      in the CG (22.6 -SD 16.1- vs. 8.6 -SD 7.2-, p = 0.001), but fewer home nursing
      visits (15.3 -SD 11.6- vs. 25.4 -SD 26.3-, respectively), though the difference
      was not statistically significant (p = 0.3603). CONCLUSIONS: This study shows
      that telemonitoring of in-home patients with HF and/or CLD notably increases the
      percentage of patients with no hospital admissions and indicates a trend to
      reduce total and cause-specific hospitalisations and hospital stay. Home
      telemonitoring can constitute a beneficial alternative mode of healthcare
      provision for medically unstable elderly patients. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN89041993.

PMID- 23537335
TI  - Soluble molybdenum(V) imido phthalocyanines and pyrazinoporphyrazines: crystal
      structure, UV-vis and electron paramagnetic resonance spectroscopic studies.
AB  - Soluble alkyl and aryl imido phthalocyanines [Pc(#)Mo(NR)Cl] (R = tBu, Mes) with
      molybdenum(V) as central metal were prepared and studied by UV-vis and electron
      paramagnetic resonance (EPR) spectroscopy. As structural analogue to the weakly
      aggregating, soluble alkyl substituted Pc(#) ligand, a new, more electron
      deficient octaazaphthalocyanine, the pyrazinoporphyrazine ligand Ppz(#), was
      designed. The respective alkyl and aryl imido complexes [Ppz(#)Mo(NR)Cl] are the
      first examples of molybdenum pyrazinoporphyrazines. UV-vis and EPR spectra
      revealed unexpected differences between the alkyl and the aryl imido complexes,
      indicating different electronic structures depending on the nature of the axial
      ligand. The octahedral coordination of the molybdenum atoms by the axial NR and
      Cl ligands and the equatorial macrocycles could be verified by EPR spectroscopy.
      This result was also confirmed by the crystal structure of [Pc(#)Mo(NMes)Cl],
      which crystallizes from CH2Cl2 in the cubic space group Im3.

PMID- 23537334
TI  - Cost effective interventions for the prevention of cardiovascular disease in low
      and middle income countries: a systematic review.
AB  - BACKGROUND: While there is good evidence to show that behavioural and lifestyle
      interventions can reduce cardiovascular disease risk factors in affluent
      settings, less evidence exists in lower income settings.This study systematically
      assesses the evidence on cost-effectiveness for preventive cardiovascular
      interventions in low and middle-income settings. METHODS:  DESIGN: Systematic
      review of economic evaluations on interventions for prevention of cardiovascular
      disease. DATA SOURCES: PubMed, Web of Knowledge, Scopus and Embase, Opensigle,
      the Cochrane database, Business Source Complete, the NHS Economic Evaluations
      Database, reference lists and email contact with experts. ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: we included economic evaluations conducted in adults,
      reporting the effect of interventions to prevent cardiovascular disease in low
      and middle income countries as defined by the World Bank. The primary outcome was
      a change in cardiovascular disease occurrence including coronary heart disease,
      heart failure and stroke. DATA EXTRACTION: After selection of the studies, data
      were extracted by two independent investigators using a previously constructed
      tool and quality was evaluated using Drummond's quality assessment score.
      RESULTS: From 9731 search results we found 16 studies, which presented economic
      outcomes for interventions to prevent cardiovascular disease in low and middle
      income settings, with most of these reporting positive cost effectiveness
      results.When the same interventions were evaluated across settings, within and
      between papers, the likelihood of an intervention being judged cost effective was
      generally lower in regions with lowest gross national income. While population
      based interventions were in most cases more cost effective, cost effectiveness
      estimates for individual pharmacological interventions were overall based upon a
      stronger evidence base. CONCLUSIONS: While more studies of cardiovascular
      preventive interventions are needed in low and mid income settings, the available
      high-level of evidence supports a wide range of interventions for the prevention
      of cardiovascular disease as being cost effective across all world regions.

PMID- 23537336
TI  - Multifractal geometry in analysis and processing of digital retinal photographs
      for early diagnosis of human diabetic macular edema.
AB  - OBJECTIVE: The purpose of this paper is to determine a quantitative assessment of
      the human retinal vascular network architecture for patients with diabetic
      macular edema (DME). Multifractal geometry and lacunarity parameters are used in
      this study. MATERIALS AND METHODS: A set of 10 segmented and skeletonized human
      retinal images, corresponding to both normal (five images) and DME states of the
      retina (five images), from the DRIVE database was analyzed using the Image J
      software. Statistical analyses were performed using Microsoft Office Excel 2003
      and GraphPad InStat software. RESULTS: The human retinal vascular network
      architecture has a multifractal geometry. The average of generalized dimensions
      (Dq) for q = 0, 1, 2 of the normal images (segmented versions), is similar to the
      DME cases (segmented versions). The average of generalized dimensions (Dq) for q
      = 0, 1 of the normal images (skeletonized versions), is slightly greater than the
      DME cases (skeletonized versions). However, the average of D2 for the normal
      images (skeletonized versions) is similar to the DME images. The average of
      lacunarity parameter, Lambda, for the normal images (segmented and skeletonized
      versions) is slightly lower than the corresponding values for DME images
      (segmented and skeletonized versions). CONCLUSION: The multifractal and
      lacunarity analysis provides a non-invasive predictive complementary tool for an
      early diagnosis of patients with DME.

PMID- 23537337
TI  - Plasma levels of apolipoprotein-E in residents of the European North of Russia.
AB  - BACKGROUND: Apolipoprotein-E (apoE) is one of the metabolically active
      apoproteins and plays an important role in lipid metabolism. However, there are
      no data on levels of apoE in residents of the North in spite of the fact that
      specific features of lipid metabolism in the northerners are described. The
      present work was designed to study plasma levels of apoE in residents of the
      European North of Russia. METHODS: A total of 937 native residents of the
      European North of Russia (463 men and 474 women) aged 13-60 years were included
      in the study. ApoE concentrations in the blood plasma were measured by
      immunoturbidimetric method. RESULTS: Plasma levels of apoE in residents of the
      European North of Russia were low. ApoE concentrations below the defined normal
      values were detected in 57.0% of the men and in 59.2% of the women. The mean
      plasma levels of apoE did not significantly differ in men and women (2.80 mg/dl
      vs 2.87 mg/dl). Plasma apoE concentrations in residents of the European North of
      Russia changed with age. Plasma levels of apoE decreased from 13 to 21 years in
      men and from 13 to 35 years in women and then increased in both sexes (p <
      0.001). CONCLUSION: The limits of variation of plasma apoE levels in residents of
      the European North of Russia shift towards lower values. Plasma levels of apoE
      below normal values were observed in approximately half of investigation
      subjects.

PMID- 23537338
TI  - Activated charcoal-mediated RNA extraction method for Azadirachta indica and
      plants highly rich in polyphenolics, polysaccharides and other complex secondary
      compounds.
AB  - BACKGROUND: High quality RNA is a primary requisite for numerous molecular
      biological applications but is difficult to isolate from several plants rich in
      polysaccharides, polyphenolics and other secondary metabolites. These compounds
      either bind with nucleic acids or often co-precipitate at the final step and many
      times cannot be removed by conventional methods and kits. Addition of vinyl
      pyrollidone polymers in extraction buffer efficiently removes polyphenolics to
      some extent, but, it failed in case of Azadirachta indica and several other
      medicinal and aromatic plants. FINDINGS: Here we report the use of adsorption
      property of activated charcoal (0.03%-0.1%) in RNA isolation procedures to remove
      complex secondary metabolites and polyphenolics to yield good quality RNA from
      Azadirachta indica. We tested and validated our modified RNA isolation method
      across 21 different plants including Andrographis paniculata, Aloe vera, Rosa
      damascena, Pelargonium graveolens, Phyllanthus amarus etc. from 13 other
      different families, many of which are considered as tough system for isolating
      RNA. The A260/280 ratio of the extracted RNA ranged between 1.8-2.0 and distinct
      28S and 18S ribosomal RNA bands were observed in denaturing agarose gel
      electrophoresis. Analysis using Agilent 2100 Bioanalyzer revealed intact total
      RNA yield with very good RNA Integrity Number. CONCLUSIONS: The RNA isolated by
      our modified method was found to be of high quality and amenable for sensitive
      downstream molecular applications like subtractive library construction and RT
      PCR. This modified RNA isolation procedure would aid and accelerate the
      biotechnological studies in complex medicinal and aromatic plants which are
      extremely rich in secondary metabolic compounds.

PMID- 23537339
TI  - Enantioselective iron-catalyzed azidation of beta-keto esters and oxindoles.
AB  - The first example of Fe-catalyzed enantioselective azidations of beta-keto esters
      and oxindoles using a readily available N3-transfer reagent is reported. A number
      of alpha-azido-beta-keto esters were obtained with up to 93% ee, and this
      methodology also generates 3-substitued 3-azidooxindoles with high
      enantioselectivities (up to 94%).

PMID- 23537340
TI  - Ziconotide: a clinical update and pharmacologic review.
AB  - INTRODUCTION: Ziconotide is an N-type calcium channel antagonist to treat chronic
      pain that is delivered intrathecally. It is the only intrathecal, FDA-approved,
      non-opioid analgesic and is recommended as first-line therapy. Despite these
      advantages, a small therapeutic window limits ziconotide's clinical utility, with
      adverse event (AE) challenges that include, but are not limited to, dizziness,
      nausea, and somulence. AREAS COVERED: Pharmacokinetics, pharmacodynamics,
      efficacy, safety, trialing, and chronic infusion after searching EMBASE, PubMed,
      and Cochrane Database of Systemic Reviews were used to search published
      literature from 1966 to January 1, 2013 to identify studies related to the
      intrathecal delivery of ziconotide. EXPERT OPINION: Ziconotide is a safe and
      effective strategy to treat chronic pain, although limitations remain, including
      a small therapeutic window. Low starting doses and slow incremental increases and
      long titration intervals may improve tolerability. AEs may be mitigated by also
      employing combination therapy, although further study is needed. Concomitant use
      of ziconotide and morphine is an option when considering use of FDA-labeled
      intrathecal drugs in those resistant to monotherapy.

PMID- 23537342
TI  - Cigarette smoking and tuberculosis in Cambodia: findings from a national sample.
AB  - BACKGROUND: Cambodia has very high rates of tuberculosis and smoked tobacco use
      among adults. Efforts to control both tobacco use and tuberculosis in Cambodia
      need to be informed by nationally representative data. Our objective is to
      examine the relation between daily cigarette smoking and lifetime tuberculosis
      (TB) history in a national sample of adults in Cambodia. METHODS: In 2011, a
      multi-stage, cluster sample of 15,615 adults (ages 15 years and older) from all
      regions of Cambodia were administered the Global Adult Tobacco Survey by
      interviewers from the National Institute of Statistics of Cambodia. RESULTS: Our
      findings include: 1) among daily smokers, a significant positive relation between
      TB and number of cigarettes smoked per day (OR = 1.70 [95% CI 1.01, 2.87]) and
      pack-years of smoking (OR = 1.53 [95% CI 1.05, 2.25]) 2) a non-significant 58%
      increase in odds of ever having being diagnosed with TB among men who smoked
      manufactured cigarettes (OR = 1.58 [95% CI 0.97, 2.58]). CONCLUSION: In Cambodia,
      manufactured cigarette smoking was associated with lifetime TB infection and the
      association was most evident among the heaviest smokers (> 1 pack per day, > 30
      pack years).

PMID- 23537341
TI  - Enhancement by interleukin-1beta of AMPA and NMDA receptor-mediated currents in
      adult rat spinal superficial dorsal horn neurons.
AB  - BACKGROUND: Proinflammatory cytokine interleukin-1beta (IL-1beta) released from
      spinal microglia plays an important role in the maintenance of acute and chronic
      pain states. However, the cellular basis of this action remains poorly
      understood. Using whole-cell patch-clamp recordings, we examined the action of IL
      1beta on AMPA- and NMDA-receptor-mediated currents recorded from substantia
      gelatinosa (SG) neurons of adult rat spinal cord slices which are key sites for
      regulating nociceptive transmission from the periphery. RESULTS: AMPA- and NMDA
      induced currents were increased in peak amplitude by IL-1beta in a manner
      different from each other in SG neurons. These facilitatory actions of IL-1beta
      were abolished by IL-1 receptor (IL-1R) antagonist (IL-1ra), which by itself had
      no detectable effects on AMPA- and NMDA-induced currents. The AMPA- but not NMDA
      induced current facilitated by IL-1beta was recovered to control level 30 min
      after IL-1beta washout and largely depressed in Na+-channel blocker tetrodotoxin
      containing or nominally Ca2+-free Krebs solution. Minocycline, a microglia
      inhibitor, blocked the facilitatory effect of IL-1beta on AMPA- but not NMDA
      induced currents, where minocycline itself depressed NMDA- but had not any
      effects on AMPA-induced currents. CONCLUSIONS: IL-1beta enhances AMPA and NMDA
      responses in SG neurons through IL-1R activation; the former but not latter
      action is reversible and due to an increase in neuronal activity in a manner
      dependent on extracellular Ca2+ and minocycline. It is suggested that AMPA and
      NMDA receptors are positively modulated by IL-1beta in a manner different from
      each other; the former but not latter is mediated by a neurotransmitter released
      as a result of an increase in neuronal activity. Since IL-1beta contributes to
      nociceptive behavior induced by peripheral nerve or tissue injury, the present
      findings also reveal an important cellular link between neuronal and glial cells
      in the spinal dorsal horn.

PMID- 23537343
TI  - CD133 expression is not an independent prognostic factor in stage II and III
      colorectal cancer but may predict the better outcome in patients with adjuvant
      therapy.
AB  - BACKGROUND: Cancer stem cells (CSCs) are notorious for their capacity of tumor
      progression, metastasis or resistance to chemo-radiotherapy. However, the
      undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not
      clear yet. METHODS: We assessed 271 surgically-resected stage II and III primary
      CRCs with (171) and without (100) adjuvant therapy after surgery. CD133
      expression was analyzed by immunohistochemical (IHC) staining and real-time RT
      PCR. CD133 promoter methylation was quantified by pyrosequencing. RESULTS: The
      CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257)
      and inversely correlated with the promoter methylation (p=0.0001). CD133 was
      expressed more frequently in rectal cancer (p=0.0035), and in moderately
      differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not
      significantly correlated with overall survival (OS) (p=0.9689) as well as disease
      free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly
      associated with better OS in patients with adjuvant therapy compared to those
      without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the
      patients with CD133- tumors did not show any significant difference of survival
      according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015).
      CONCLUSIONS: In stage II and III CRCs, CD133 IHC expression may signify the
      benefit for adjuvant therapy although it is not an independent prognostic factor.

PMID- 23537344
TI  - Impact of pulmonary rehabilitation on the major dimensions of dyspnea in COPD.
AB  - The evaluation of dyspnea and its responsiveness to therapy in COPD should
      consider the multidimensional nature of this symptom in each of its sensory
      perceptual (intensity, quality), affective and impact domains. To gain new
      insights into mechanisms of dyspnea relief following pulmonary rehabilitation
      (PR), we examined effects on the major domains of dyspnea and their interaction
      with physiological training effects. This randomized, controlled study was
      conducted in 48 subjects with COPD. Subjects received either 8-weeks of PR or
      usual care (CTRL). Pre- and post-intervention assessments included: sensory
      perceptual (i.e., exertional dyspnea intensity, dyspnea descriptors at end
      exercise), affective (i.e., intensity of breathing-related anxiety during
      exercise, COPD self-efficacy, walking self-efficacy) and impact (i.e., activity
      related dyspnea measured by the Baseline/Transition Dyspnea Index, Chronic
      Respiratory Questionnaire dyspnea component, St. George's Respiratory Disease
      Questionnaire activity component) domains of dyspnea; functional performance
      (i.e., 6-minute walk, endurance shuttle walk); pulmonary function; and
      physiological measurements during constant work rate cycle exercise at 75% of the
      peak incremental work rate. Forty-one subjects completed the study: PR (n = 17)
      and CTRL (n = 24) groups were well matched for age, sex, body size and pulmonary
      function. There were no significant between-group differences in pre- to post
      intervention changes in pulmonary function or physiological parameters during
      exercise. After PR versus CTRL, significant improvements were found in the
      affective and impact domains but not in the sensory-perceptual domain of dyspnea.
      In conclusion, clinically meaningful improvements in the affective and impact
      domains of dyspnea occurred in response to PR in the absence of consistent
      physiological training effects.

PMID- 23537345
TI  - The epidemiology of anaphylaxis in Europe: protocol for a systematic review.
AB  - BACKGROUND: The European Academy of Allergy and Clinical Immunology is in the
      process of developing its Guideline for Food Allergy and Anaphylaxis, and this
      systematic review is one of seven inter-linked evidence syntheses that are being
      undertaken in order to provide a state-of-the-art synopsis of the current
      evidence base in relation to epidemiology, prevention, diagnosis and clinical
      management and impact on quality of life, which will be used to inform clinical
      recommendations.The aims of this systematic review will be to understand and
      describe the epidemiology of anaphylaxis, i.e. frequency, risk factors and
      outcomes of anaphylaxis, and describe how these characteristics vary by person,
      place and time. METHODS: A highly sensitive search strategy has been designed to
      retrieve all articles combining the concepts of anaphylaxis and epidemiology from
      electronic bibliographic databases. DISCUSSION: This review will aim to provide
      some estimates of the incidence and prevalence of anaphylaxis in Europe. The
      occurrence of anaphylaxis can have a profound effect on the quality of life of
      the sufferer and their family. Estimates of disease frequency will help us to
      ascertain the burden of anaphylaxis and provide useful comparators for management
      strategies.

PMID- 23537346
TI  - Bovine HEXIM1 inhibits bovine immunodeficiency virus replication through
      regulating BTat-mediated transactivation.
AB  - The bovine immunodeficiency virus (BIV) transactivator (BTat) recruits the bovine
      cyclin T1 (B-cyclin T1) to the LTR to facilitate the transcription of BIV. Here,
      we demonstrate that bovine hexamethylene bisacetamide (HMBA)-induced protein 1
      (BHEXIM1) inhibits BTat-mediated BIV LTR transcription. The results of in vivo
      and in vitro assays show direct binding of BHEXIM1 to the B-cyclin T1. These
      results suggest that the repression arises from BHEXIM1-BTat competition for B
      cyclin T1, which allows BHEXIM1 to displace BTat from B-cyclin T1. Furthermore,
      we found that the C-terminal region and the centrally located region of BHEXIM1
      are required for BHEXIM1 to associate with B-cyclin T1. Knockdown of BHEXIM1
      enhances BIV replication. Taken together, our study provides the first clear
      evidence that BHEXIM1 is involved in BIV replication through regulating BTat
      mediated transactivation.

PMID- 23537348
TI  - Competing with the conventional wisdom: newspaper framing of medical
      overtreatment.
AB  - Overtreatment, defined as the use of medical tests, products, and services that
      are not medically necessary or beneficial to the patient, may account for as much
      as 30% of all U.S. health care expenditures. This article describes a study of
      the framing of this important health and economic issue in elite U.S. newspapers
      from January 1, 2007, through December 31, 2010. Within 98 articles providing
      some mention of overtreatment, analysis revealed three major frames: uncertainty,
      cost, and legal issues. Within the uncertainty frame, there was a remarkable
      emphasis on cancer testing and treatment as a driver of overutilization, which
      may suggest to readers that overtreatment does not occur or is not important in
      other types of medical care. Relatively few stories paid much attention to the
      financial costs of overtreatment. 

PMID- 23537347
TI  - An effective method for refining predicted protein complexes based on protein
      activity and the mechanism of protein complex formation.
AB  - BACKGROUND: Identifying protein complexes from protein-protein interaction
      network is fundamental for understanding the mechanism of cellular component and
      protein function. At present, many methods to identify protein complexes are
      mainly based on the topological characteristics or the functional similarity
      features, neglecting the fact that proteins must be in their active forms to
      interact with others and the formation of protein complex is following a just-in
      time mechanism. RESULTS: This paper firstly presents a protein complex formation
      model based on the just-in-time mechanism. By investigating known protein
      complexes combined with gene expression data, we find that most protein complexes
      can be formed in continuous time points, and the average overlapping rate of the
      known complexes during the formation is large. A method is proposed to refine the
      protein complexes predicted by clustering algorithms based on the protein complex
      formation model and the properties of known protein complexes. After refinement,
      the number of known complexes that are matched by predicted complexes,
      Sensitivity, Specificity, and f-measure are significantly improved, when compared
      with those of the original predicted complexes. CONCLUSION: The refining method
      can discard the spurious proteins by protein activity and generate new complexes
      by just-in-time assemble mechanism, which can enhance the ability to predict
      complex.

PMID- 23537349
TI  - Partial loss of CovS function in Streptococcus pyogenes causes severe invasive
      disease.
AB  - BACKGROUND: CovRS (or CsrRS) is a two-component regulatory system that regulates
      the production of multiple virulence factors in Streptococcus pyogenes. covS
      mutations are often found in isolates recovered from mice that have been
      experimentally infected with S. pyogenes and covS mutations enhance bacterial
      virulence in an invasive infection mouse model. In addition, covS mutations were
      detected more frequently in a panel of clinical isolates from severe invasive
      streptococcal infections than those from non-severe infections. Thus, covS
      mutations may be associated with the onset of severe invasive infections.
      RESULTS: Known covS mutations were divided into two groups: (i) frameshift
      mutations that caused a deletion of functional regions and (ii) point mutations
      that caused single (or double) amino acid(s) substitutions. Frameshift mutations
      are frequent in mouse-passaged isolates, whereas point mutations are frequent in
      clinical isolates. The functions of CovS proteins with a single amino acid
      substitution in clinical isolates were estimated based on the streptococcal
      pyrogenic exotoxin B (SpeB) production and NAD+-glycohydrolase (NADase) activity,
      which are known to be regulated by the CovRS system. Point mutations partially,
      but not completely, impaired the function of the covS alleles. We also
      investigated some of the benefits that a partial loss of function in covS alleles
      with point mutations might confer on clinical isolates. We found that covS
      knockout mutants (DeltacovS strains) had an impaired growth ability in a normal
      atmosphere in Todd Hewitt broth compared with parental isolates having wild-type
      or point-mutated covS. CONCLUSIONS: The loss of CovS proteins in S. pyogenes may
      confer greater virulence, but bacteria may also lose the ability to respond to
      certain external signals recognized by CovS. Therefore, point mutations that
      retain the function of CovS and confer hypervirulence may have natural selective
      advantages.

PMID- 23537350
TI  - A systematic review of the care coordination measurement landscape.
AB  - BACKGROUND: Care coordination has increasingly been recognized as an important
      aspect of high-quality health care delivery. Robust measures of coordination
      processes will be essential tools to evaluate, guide and support efforts to
      understand and improve coordination, yet little agreement exists among
      stakeholders about how to best measure care coordination. We aimed to review and
      characterize existing measures of care coordination processes and identify areas
      of high and low density to guide future measure development. METHODS: We
      conducted a systematic review of measures published in MEDLINE through April 2012
      and identified from additional key sources and informants. We characterized
      included measures with respect to the aspects of coordination measured (domain),
      measurement perspective (patient/family, health care professional, system
      representative), applicable settings and patient populations (by age and
      condition), and data used (survey, chart review, administrative claims). RESULTS:
      Among the 96 included measure instruments, most relied on survey methods (88%)
      and measured aspects of communication (93%), in particular the transfer of
      information (81%). Few measured changing coordination needs (11%). Nearly half
      (49%) of instruments mapped to the patient/family perspective; 29% to the system
      representative and 27% to the health care professionals perspective. Few
      instruments were applicable to settings other than primary care (58%), inpatient
      facilities (25%), and outpatient specialty care (22%). CONCLUSIONS: New measures
      are needed that evaluate changing coordination needs, coordination as perceived
      by health care professionals, coordination in the home health setting, and for
      patients at the end of life.

PMID- 23537351
TI  - Tuning the Dirac point in CVD-grown graphene through solution processed n-type
      doping with 2-(2-methoxyphenyl)-1,3-dimethyl-2,3-dihydro-1H-benzoimidazole.
AB  - Controlling the Dirac point of graphene is essential for complementary circuits.
      Here, we describe the use of 2-(2-methoxyphenyl)-1,3-dimethyl-2,3-dihydro-1H
      benzoimidazole (o-MeO-DMBI) as a strong n-type dopant for chemical-vapor
      deposition (CVD) grown graphene. The Dirac point of graphene can be tuned
      significantly by spin-coating o-MeO-DMBI solutions on the graphene sheets at
      different concentrations. The transport of graphene can be changed from p-type to
      ambipolar and finally n-type. The electron transfer between o-MeO-DMBI and
      graphene was additionally confirmed by Raman imaging and photoemission
      spectroscopy (PES) measurements. Finally, we fabricated a complementary inverter
      via inkjet printing patterning of o-MeO-DMBI solutions on graphene to demonstrate
      the potential of o-MeO-DMBI n-type doping on graphene for future applications in
      electrical devices.

PMID- 23537352
TI  - Growing bone tissue-engineered niches with graded osteogenicity: an in vitro
      method for biomimetic construct assembly.
AB  - The traditional bone tissue-engineering approach exploits mesenchymal stem cells
      (MSCs) to be seeded once only on three-dimensional (3D) scaffolds, hence,
      differentiated for a certain period of time and resulting in a homogeneous
      osteoblast population at the endpoint. However, after achieving terminal
      osteodifferentiation, cell viability is usually markedly compromised. On the
      other hand, naturally occurring osteogenesis results from the coexistence of MSC
      progenies at distinct differentiative stages in the same microenvironment. This
      diversification also enables long-term viability of the mature tissue. We report
      an easy and tunable in vitro method to engineer simple osteogenic cell niches in
      a biomimetic fashion. The niches were grown via periodic reseeding of
      undifferentiated MSCs on MSC/scaffold constructs, the latter undergoing
      osteogenic commitment. Time-fractioning of the seeded cell number during
      differentiation time of the constructs allowed graded osteogenic cell populations
      to be grown together on the same scaffolds (i.e., not only terminally
      differentiated osteoblasts). In such cell-dynamic systems, the overall
      differentiative stage of the constructs could also be tuned by varying the cell
      density seeded at each inoculation. In this way, we generated two different
      biomimetic niche models able to host good reservoirs of preosteoblasts and other
      osteoprogenitors after 21 culture days. At that time, the niche type resulting in
      40.8% of immature osteogenic progenies and only 59.2% of mature osteoblasts
      showed a calcium content comparable to the constructs obtained with the
      traditional culture method (i.e., 100.03 +/- 29.30 vs. 78.51 +/- 28.50 pg/cell,
      respectively; p=not significant), the latter colonized only by fully
      differentiated osteoblasts showing exhausted viability. This assembly method for
      tissue-engineered constructs enabled a set of important parameters, such as
      viability, colonization, and osteogenic yield of the MSCs to be balanced on 3D
      scaffolds, thus achieving biomimetic in vitro models with graded osteogenicity,
      which are more complex and reliable than those currently used by tissue
      engineers.

PMID- 23537353
TI  - The demarcation of intellectual disability.

PMID- 23537354
TI  - What's at stake in the lives of people with intellectual disability? Part I: The
      power of naming, defining, diagnosing, classifying, and planning supports.
AB  - This article focuses on the power of naming, defining, diagnosing, classifying,
      and planning supports for people with intellectual disability. The article
      summarizes current thinking regarding these five functions, states the essential
      question addressed by the respective function, and provides an overview of the
      high stakes involved for people with intellectual disability, their families, and
      the field of intellectual disability.

PMID- 23537355
TI  - What's at stake in the lives of people with intellectual disability? Part II:
      Recommendations for naming, defining, diagnosing, classifying, and planning
      supports.
AB  - This article focuses on recommendations for naming, defining, diagnosing,
      classifying, and planning supports for individuals with intellectual disability
      (ID). The article provides an overview of the essential questions addressed by
      the respective functions and provides a series of specific recommendations that
      address the high stakes involved for people with ID, their families, and the
      field of ID.

PMID- 23537356
TI  - The law's understanding of intellectual disability as a disability.
AB  - Intellectual disability (ID) is differently yet validly described by different
      professions. Legal professionals find it most useful to consider ID as a
      disability rather than a disorder. Because the law regulates the actions of
      individuals in a society and the actions of society on an individual, the law's
      concern in dealing with a person with ID is almost always with that person's
      functional abilities and limitations in society. This concern is reflected in
      various aspects of criminal and civil law, although the methods of assessing
      those functional abilities and limitations have changed considerably over time.
      The law has not always been wise or humane in its treatment of people with ID,
      but its focus on functional abilities and limitations allows us to assist people
      with ID to use their abilities and participate in society to their fullest
      potential.

PMID- 23537357
TI  - Beyond terminology: the policy impact of a grassroots movement.
AB  - This article discusses the history of the grassroots movement led by self
      advocates and their families to replace the stigmatizing term "mental
      retardation" with "intellectual disability" in federal statute. It also describes
      recent and pending changes in federal regulations and policy to adopt the new
      terminology for Social Security and Medicaid.

PMID- 23537358
TI  - What's in a name?
AB  - The World Health Organization (WHO) is in the process of developing the 11th
      edition of the International Classification of Diseases (ICD-11). Part of this
      process includes replacing mental retardation with a more acceptable term to
      identify the condition. The current international consensus appears to be
      replacing "mental retardation" with "intellectual disability". This article
      briefly presents some of the issues involved in changing terminology and the
      constraints and conventions that are specific to the ICD.

PMID- 23537359
TI  - Definition of intellectual disability in criminal court cases.
AB  - Definitions and associated descriptions of the condition now commonly known as
      intellectual disability serve many functions. The Atkins v. Virginia U.S. Supreme
      Court decision (2002) has called attention to the importance of clear, objective,
      and measureable wording of the definition. This article discusses the potential
      for misunderstanding and misinterpretation of such words as ability and
      cognitive, the importance of clarifying the role of measurement error and
      sociocultural factors, and the noncausal relationship between impairment in
      intelligence and adaptive behavior.

PMID- 23537360
TI  - Disability, disorder, and identity.
AB  - The World Health Organization's International Classification of Diseases (ICD) is
      the most important diagnostic tool, worldwide, to ensure that people with
      intellectual and developmental disabilities receive the supports they need to
      live richer, fuller lives. And yet, the ICD has naming conventions that create a
      conundrum for the field, requiring that all "conditions" in the ICD be named as a
      "disorder." This article discusses the effect of naming on how people with
      intellectual disability are perceived by others and how they perceive themselves.
      The importance of continuing to move the field toward the adoption of
      functional/person-environment fit models of disability is discussed.

PMID- 23537361
TI  - AAIDD proposed recommendations for ICD-11 and the condition previously known as
      mental retardation.
AB  - The World Health Organization (WHO) is in the process of seeking input from
      professional stakeholder groups and consumers regarding the draft proposals of
      the 11th edition of the International Classification of Diseases (ICD-11). The
      American Association on Intellectual and Developmental Disabilities (AAIDD)
      convened a small group of distinguished interdisciplinary expert professionals in
      intellectual disability to review the ICD-11 proposal regarding revisions of the
      condition previously known as "mental retardation." This article presents the
      recommendations made by the AAIDD to the WHO Secretariat regarding the name,
      definition, diagnostic guidelines, and classification of the condition known
      today as intellectual disability.

PMID- 23537362
TI  - Considering context: an integrative concept for promoting outcomes in the
      intellectual disability field.
AB  - Abstract In light of the rapid evolution of research, policy, and practice in the
      intellectual disability (ID) field resulting from shifts in our conceptualization
      of disability and in frameworks for the diagnosis and classification of ID,
      systematic consideration of the multiple, interrelated contextual factors that
      impact research, policy, and practice are necessary to achieve valued outcomes
      for individuals with disabilities, their families, and society. The purpose of
      this article is to introduce a recently developed consensus definition of context
      and elaborate on application of this definition to research, practice, and policy
      in the ID field, with a specific focus on how context may be able to serve as an
      integrative concept to support the attainment of valued outcomes in the
      disability field for individuals with disabilities, their families, and society.

PMID- 23537364
TI  - MDR1 polymorphisms are associated with inflammatory bowel disease in a cohort of
      Croatian IBD patients.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are chronic diseases of unknown
      etiology and pathogenesis in which genetic factors contribute to development of
      disease. MDR1/ABCB1 is an interesting candidate gene for IBD. The role of two
      single nucleotide polymorphisms, C3435T and G2677T remains unclear due to
      contradictory results of current studies. Thus, the aims of this research were to
      investigate the association of MDR1 polymorphisms, C3435T and G2677T, and IBD.
      METHODS: A total of 310 IBD patients, 199 Crohn's disease (CD) patients and 109
      ulcerative colitis (UC) patients, and 120 healthy controls were included in the
      study. All subjects were genotyped for G2677T/A and C3435T polymorphism using RT
      PCR. In IBD patients, review of medical records was performed and patients were
      phenotyped according to the Montreal classification. RESULTS: Significantly
      higher frequency of 2677T allele (p=0.05; OR 1.46, 95% CI (1.0-2.14)) and of the
      3435TT genotype was observed among UC patients compared to controls (p=0.02; OR
      2.12; 95% CI (1.11-4.03). Heterozygous carriers for C3435T were significantly
      less likely to have CD (p=0.02; OR 0.58, 95% CI (0.36-0.91)). Haplotype analysis
      revealed that carriers of 3435T/2677T haplotype had a significantly higher risk
      of having UC (p=0.02; OR 1.55; 95% CI (1.06-2.28)). CONCLUSION: MDR1
      polymorphisms are associated with both CD and UC with a stronger association with
      UC.

PMID- 23537366
TI  - Unprecedented tris-phosphido-bridged triangular clusters with 42 valence
      electrons. Chemical, electrochemical and computational studies of their formation
      and stability.
AB  - This paper presents the synthesis and structural characterization of the
      unprecedented tris-phosphido-bridged compounds Pt3(MU-PBu(t)2)3X3 (X = Cl, Br,
      I), having only 42 valence electrons, while up to now analogous clusters
      typically have 44e(-). The new species were obtained by an apparent bielectronic
      oxidation of the 44e(-) monohalides Pt3(MU-PBu(t)2)3(CO)2X with the corresponding
      dihalogen X2. Their X-ray structures are close to the D3h symmetry, similarly to
      the 44e(-) analogues with three terminal carbonyl ligands. The products were also
      obtained by electrochemical oxidation of the same monohalides in the presence of
      the corresponding halide. In a detailed study on the formation of Pt3(MU
      PBu(t)2)3I3, the redox potentials indicated that I2 can only perform the first
      monoelectronic oxidation but is unsuited for the second one. Accordingly, the
      43e(-) intermediate [Pt3(MU-PBu(t)2)3(CO)2I](+) was ascertained to play a key
      role. Another piece of information is that, together with the fully oxidized
      product Pt3(MU-PBu(t)2)3I3, the transient 44e(-) species [Pt3(MU
      PBu(t)2)3(CO)3](+) is formed in the early steps of the reaction. In order to
      extract detailed information on the formation pathway, involving both terminal
      ligand substitutions and electron transfer processes, a DFT investigation has
      been performed and all the possible intermediates have been defined together with
      their associated energy costs. The profile highlights many important aspects,
      such as the formation of an appropriate couple of 43e(-) intermediates having
      different sets of terminal coligands, and suitable redox potentials for the
      transfer of one electron. Optimizations of 45e(-) associative intermediates in
      the ligand substitution reactions indicate their possible involvement in the
      redox process with reduction of the overall energy cost. Finally, according to MO
      arguments, the unique stability of the 42e(-) phosphido-bridged Pt3 clusters can
      be attributed to the simultaneous presence of three terminal halides.

PMID- 23537365
TI  - Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early
      clinical drug development.
AB  - BACKGROUND: Inhalation of endotoxin (LPS) induces a predominantly neutrophilic
      airway inflammation and has been used as model to test the anti-inflammatory
      activity of novel drugs. In the past, a dose exceeding 15-50 MUg was generally
      needed to induce a sufficient inflammatory response. For human studies,
      regulatory authorities in some countries now request the use of GMP-grade LPS,
      which is of limited availability. It was therefore the aim of this study to test
      the effect and reproducibility of a low-dose LPS challenge (20,000 E.U.; 2 MUg)
      using a flow- and volume-controlled inhalation technique to increase LPS
      deposition. METHODS: Two to four weeks after a baseline sputum induction, 12 non
      smoking healthy volunteers inhaled LPS on three occasions, separated by at least
      4 weeks. To modulate the inflammatory effect of LPS, a 5-day PDE4 inhibitor
      (Roflumilast) treatment preceded the last challenge. Six hours after each LPS
      inhalation, sputum induction was performed. RESULTS: The low-dose LPS inhalation
      was well tolerated and increased the mean percentage of sputum neutrophils from
      25% to 72%. After the second LPS challenge, 62% neutrophils and an increased
      percentage of monocytes were observed. The LPS induced influx of neutrophils and
      the cumulative inflammatory response compared with baseline were reproducible.
      Treatment with Roflumilast for 5 days did not have a significant effect on sputum
      composition. CONCLUSION: The controlled inhalation of 2 MUg GMP-grade LPS is
      sufficient to induce a significant neutrophilic airway inflammation in healthy
      volunteers. Repeated low-dose LPS challenges potentially result in a small shift
      of the neutrophil/monocyte ratio; however, the cumulative response is
      reproducible, enabling the use of this model for "proof-of-concept" studies for
      anti-inflammatory compounds during early drug development.

PMID- 23537367
TI  - Fiber-free white flour with fructose offers a better model of metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome (MS) is a combination of metabolic
      abnormalities that lead to an increased risk of cardiovascular diseases. Due to
      its rising incidence and demanding life-long use of multiple drugs, there is a
      growing interest in testing and developing new allopathic, complementary and
      alternative therapies for controlling or curing disorders of MS. The discovery of
      new therapeutic modalities requires animal models of disease and currently
      available models have limitations. Developing an appropriate animal model for MS
      to achieve various therapeutic targets remains a challenge and this study aims to
      develop a rat model which closely depicts MS in humans. METHODOLOGY: Rat model of
      MS was developed by replacing 60% of diet with fructose. Four groups of Sprague
      Dawley rats were either given whole wheat or refined flour with and without
      fructose for 8 weeks. Data were analyzed on SPSS and Graphpad Prism using ANOVA
      with Tukey's and Bonferonni tests for multiple group comparison. A p-value of
      less than 0.05 was considered significant for differences between groups.
      RESULTS: Replacing whole wheat with refined wheat flour in rat chow in 60%
      fructose-fed Sprague-Dawley rats resulted in hypertension (p 0.01), hyper
      insulinemia (p < 0.001), hyperglycemia (p 0.03) and a reduction in HDL levels (p
      0.002) at 4 weeks while hyper-triglyceridemia (p 0.001) with endothelial
      dysfunction was observed at 8 weeks. CONCLUSION: It is concluded that the refined
      wheat flour with 60% fructose in diet hastens the development of metabolic
      syndrome in 4 weeks and replacing whole wheat flour with refined flour in diet
      induces a more effective abnormality including a low HDL. Further studies may be
      directed to assess the associated pathological changes, which can be used to
      study the effect of different therapeutic modalities on an animal model of MS
      with low HDL.

PMID- 23537368
TI  - A review of rescue regimens after clarithromycin-containing triple therapy
      failure (for Helicobacter pylori eradication).
AB  - INTRODUCTION: Helicobacter pylori infection is generally treated with therapies
      that include a proton pump inhibitor (PPI) and, at least, two antibiotics being
      clarithromycin one of the most used. Antibiotic resistance, mainly to
      clarithromycin, seems to be increasing in many geographical areas, and this
      factor is considered a main cause leading to a treatment failure when the later
      therapies contain this antibiotic again. As clarithromycin is a key antibiotic in
      the eradication of H. pylori, the election of the rescue treatment is a matter of
      debate. AREAS COVERED: The aim of this study is to systematically review the
      efficacy of the second-line rescue therapies after the failure of a first-line
      clarithromycin-containing regimen, and to link this information with the previous
      first-line treatment. Also, authors performed meta-analyses and inverse variance
      analyses with studies that met the inclusion criteria: first-line treatment must
      specify type and dosage; diagnosis and eradication confirmation must be performed
      by generally accepted tests; and second-line treatment must not be assigned
      depending on the antibiotic susceptibility or resistance. EXPERT OPINION: In a
      routine clinical practice setting, the most adequate second-line treatment
      consists in a 10-day regimen of levofloxacin- amoxicillin-PPI given twice daily,
      unless regional or new data show high quinolone resistance. Other good options
      are the bismuth quadruple regimen and a metronidazole-amoxicillin-PPI therapy.

PMID- 23537370
TI  - C-N bond cleavage of anilines by a (salen)ruthenium(VI) nitrido complex.
AB  - We report experimental and computational studies of the facile oxidative C-N bond
      cleavage of anilines by a (salen)ruthenium(VI) nitrido complex. We provide
      evidence that the initial step involves nucleophilic attack of aniline at the
      nitrido ligand of the ruthenium complex, which is followed by proton and electron
      transfer to afford a (salen)ruthenium(II) diazonium intermediate. This
      intermediate then undergoes unimolecular decomposition to generate benzene and
      N2.

PMID- 23537369
TI  - Preclinical studies of low back pain.
AB  - Chronic low back pain is a major cause of disability and health care costs.
      Current treatments are inadequate for many patients. A number of preclinical
      models have been developed that attempt to mimic aspects of clinical conditions
      that contribute to low back pain. These involve application of nucleus pulposus
      material near the lumbar dorsal root ganglia (DRG), chronic compression of the
      DRG, or localized inflammation of the DRG. These models, which are primarily
      implemented in rats, have many common features including behavioral
      hypersensitivity of the hindpaw, enhanced excitability and spontaneous activity
      of sensory neurons, and locally elevated levels of inflammatory mediators
      including cytokines. Clinically, epidural injection of steroids (glucocorticoids)
      is commonly used when more conservative treatments fail, but clinical trials
      evaluating these treatments have yielded mixed results. There are relatively few
      preclinical studies of steroid effects in low back pain models. One preclinical
      study suggests that the mineralocorticoid receptor, also present in the DRG, may
      have pro-inflammatory effects that oppose the activation of the glucocorticoid
      receptor. Although the glucocorticoid receptor is the target of anti-inflammatory
      steroids, many clinically used steroids activate both receptors. This could be
      one explanation for the limited effects of epidural steroids in some patients.
      Additional preclinical research is needed to address other possible reasons for
      limited efficacy of steroids, such as central sensitization or presence of an
      ongoing inflammatory stimulus in some forms of low back pain.

PMID- 23537371
TI  - Incidence of unplanned return to the operating room following vitreoretinal
      surgery at a public teaching hospital.
AB  - PURPOSE: To determine the incidence of unplanned return to the operating room
      within 30 or 90 d following vitreoretinal surgery. METHODS: Hospital records of
      431 patients undergoing vitreoretinal surgery at San Francisco General Hospital
      between 1 January 1998 and 31 December 2009 were reviewed to determine the
      incidence of unplanned reoperations. RESULTS: Unplanned reoperation occurred
      within 30 d in 22 cases (3.77%) and within 90 d in 56 cases (9.61%). CONCLUSIONS:
      This study establishes benchmarks for the rate of unplanned return to the
      operating room following vitreoretinal surgery at an urban teaching hospital.
      Measuring reoperation within 90 d may provide a useful quality improvement metric
      of short- and middle-term complications.

PMID- 23537373
TI  - Open questions: reflections on plant development and genetics.

PMID- 23537372
TI  - UCN-01 induces S and G2/M cell cycle arrest through the p53/p21(waf1) or
      CHK2/CDC25C pathways and can suppress invasion in human hepatoma cell lines.
AB  - BACKGROUND: UCN-01 (7-hydroxystaurosporine), a protein kinase inhibitor, has
      attracted a great deal of attention as a potent antitumour agent. Several
      clinical trials of UCN-01 alone or in combination with other agents for different
      tumour types are currently underway, and some of these trials have had positive
      results. Hepatocellular carcinoma has high incidence rates and is associated with
      poor prognosis and high mortality rates. METHODS: Three different hepatoma cell
      lines (Huh7, HepG2, and Hep3B) were treated with different concentrations of UCN
      01, and the anti-tumour effects of UCN-01 were evaluated. Following UCN-01
      treatment, cell growth was measured using an MTT assay, cell cycle arrest was
      assayed using flow cytometry, and the mechanisms of cell cycle arrest and
      invasion inhibition were investigated through western blotting and a Matrigel
      invasion assay. RESULTS: After a 72-h UCN-01 treatment, the growth of different
      hepatoma cell lines was significantly inhibited in a dose-dependent manner, with
      IC50 values ranging from 69.76 to 222.74 nM. Flow cytometry results suggested
      that UCN-01 inhibits proliferation in the hepatoma cells by inducing S and G2/M
      phase arrest, but not G1/S arrest, which differs from previous reports that used
      other tumour cell lines. Western blot results illustrated that UCN-01 induces a
      G2/M phase arrest, regardless of the status of the p53/P21(waf1) pathway, whereas
      the CHK2/CDC25C pathway and the p53/p21(waf1)pathway were involved in the UCN-01
      induced S phase arrest. UCN-01 remarkably inhibited Huh7 cell invasion in a time
      dependent manner. Suppression of Huh7 cell invasion may be due to the down
      regulation of phosphorylated beta-catenin by UCN-01. CONCLUSIONS: These findings
      suggest that UCN-01 induces hepatoma cell growth inhibition by regulating the
      p53/p21(waf1) and CHK2/CDC25 pathways. Suppression of Huh7 cell invasion by UCN
      01 may be due to the down-regulation of phosphorylated beta-catenin. These data
      lend support for further studies on UCN-01 as a promising anti-HCC candidate.

PMID- 23537374
TI  - Methotrexate toxicity presenting as cutaneous ulcerations on psoriatic plaques.
AB  - Methotrexate (MTX) is an effective but potentially toxic treatment for psoriasis.
      We describe a patient who administered 20 mg daily of MTX for 5 d and presented
      with ulcerated and necrotic lesions on the psoriatic plaques, mouth erosions and
      hair loss. However, his psoriatic plaques and ulcerations totally healed rapidly
      within two weeks and no recurrence has been observed for the 6 months of follow
      up.

PMID- 23537375
TI  - Development and use of a polarized equine upper respiratory tract mucosal explant
      system to study the early phase of pathogenesis of a European strain of equine
      arteritis virus.
AB  - The upper respiratory tract mucosa represents the first line of defense, which
      has to be overcome by pathogens before invading the host. Considering the
      economic and ethical aspects involved in using experimental animals for
      pathogenesis studies, respiratory mucosal explants, in which the tissue's three
      dimensional architecture is preserved, may be ideal alternatives. Different
      respiratory mucosal explant cultures have been developed. However, none of them
      could be inoculated with pathogens solely at the epithelium side. In the present
      study, equine nasal and nasopharyngeal explants were embedded in agarose (3%),
      leaving the epithelium side exposed to allow apical inoculation. Morphometric
      analysis did not show degenerative changes during 72 h of cultivation. The number
      of apoptotic cells in the mucosa slightly increased over time. After validation,
      the system was used for apical infection with a European strain (08P178) of
      equine arteritis virus (EAV) (107.6TCID50/mL per explant). Impermeability of
      agarose to virus particles was demonstrated by the absence of labeled
      microspheres (40 nm) and a lack of EAV-antigens in RK13 cells seeded underneath
      the agarose layer in which inoculated explants were embedded. At 72 hpi, 27% of
      the EAV-positive cells were CD172a+ and 19% were CD3+ in nasal explants and 45%
      of the EAV-positive cells were CD172a+ and 15% were CD3+ in nasopharyngeal
      explants. Only a small percentage of EAV-positive cells were IgM+. This study
      validates the usefulness of a polarized mucosal explant system and shows that
      CD172a+ myeloid cells and CD3+ T lymphocytes represent important EAV-target cells
      in the respiratory mucosa.

PMID- 23537376
TI  - Social brain dysfunctions in patients with Parkinson's disease: a review of
      theory of mind studies.
AB  - Human social interaction is essential in daily life and crucial for a promising
      life, especially in people who suffer from disease. Theory of Mind (ToM) is
      fundamental in social interaction and is described as the ability to impute the
      mental states of others in social situations. Studies have proposed that a
      complex neuroanatomical network that includes the frontal cortex mediates ToM.
      The primary neuropathology of Parkinson's disease (PD) involves the frontal
      striatal system; therefore, patients with PD are expected to exhibit deficits in
      ToM. In this review, we summarize the current research with a particular focus on
      the patterns of impaired ToM, potential mediators of ToM, and the impact of ToM
      deficits on clinical disability in PD. Further studies to investigate the
      progression of ToM and its relationship with dementia in subjects in PD are
      needed.

PMID- 23537377
TI  - Lipopolysaccharide interactions of C-terminal peptides from human thrombin.
AB  - Interactions with bacterial lipopolysaccharide (LPS), both in aqueous solution
      and in lipid membranes, were investigated for a series of amphiphilic peptides
      derived from the C-terminal region of human thrombin, using ellipsometry, dual
      polarization interferometry, fluorescence spectroscopy, circular dichroism (CD),
      dynamic light scattering, and z-potential measurements. The ability of these
      peptides to block endotoxic effects caused by LPS, monitored through NO
      production in macrophages, was compared to peptide binding to LPS and its
      endotoxic component lipid A, and to size, charge, and secondary structure of
      peptide/LPS complexes. While the antiendotoxic peptide GKY25
      (GKYGFYTHVFRLKKWIQKVIDQFGE) displayed significant binding to both LPS and lipid
      A, so did two control peptides with either selected D-amino acid substitutions or
      with maintained composition but scrambled sequence, both displaying strongly
      attenuated antiendotoxic effects. Hence, the extent of LPS or lipid A binding is
      not the sole discriminant for the antiendotoxic effect of these peptides. In
      contrast, helix formation in peptide/LPS complexes correlates to the
      antiendotoxic effect of these peptides and is potentially linked to this
      functionality. Preferential binding to LPS over lipid membrane was furthermore
      demonstrated for these peptides and preferential binding to the lipid A moiety
      within LPS inferred.

PMID- 23537378
TI  - Oral information about side effects of endocrine therapy for early breast cancer
      patients at initial consultation and first follow-up visit: an online survey.
AB  - This study was initiated to identify how physicians inform women about specific
      side effects of endocrine therapy for early breast cancer. It is recommended that
      women with early breast cancer receive endocrine treatment for at least 5 years.
      Although this medication is an important step in curing breast cancer, continued
      application by patients is far below 100%; 30-50% of all women prematurely end
      their prescribed therapy. In an online survey, physicians specializing in
      treating breast cancer (members of the Austrian Breast and Colorectal Cancer
      Study Group, ABCSG) were asked about their practice of informing patients about
      potential side effects of endocrine therapy for breast cancer. Two hundred and
      five members of the ABCSG completed the online questionnaire. The physicians
      indicated that patients were primarily informed regarding joint pain/muscle pain
      and flushes/sleep disturbances during the initial consultation as well as during
      the first follow-up visit. Patients were informed considerably less regarding
      side effects that influence quality-of-life areas, such as pain during
      intercourse, reduced orgasm capability, and hair loss. During the initial
      consultation, and during first follow-up visit, patients are not uniformly and
      are insufficiently informed about substantial side effects of endocrine therapy. 

PMID- 23537380
TI  - Family therapy sessions with refugee families; a qualitative study.
AB  - BACKGROUND: Due to the armed conflicts in the Balkans in the 1990s many families
      escaped to other countries. The main goal of this study was to explore in more
      detail the complexity of various family members' experiences and perceptions from
      their life before the war, during the war and the escape, and during their new
      life in Sweden. There is insufficient knowledge of refugee families' perceptions,
      experiences and needs, and especially of the complexity of family perspectives
      and family systems. This study focused on three families from Bosnia and
      Herzegovina who came to Sweden and were granted permanent residence permits. The
      families had at least one child between 5 and 12 years old. METHOD: Family
      therapy sessions were videotaped and verbatim transcriptions were made. Nine
      family therapy sessions were analysed using a qualitative method with directed
      content analysis. RESULTS: Three main categories and ten subcategories were found
      - 1. Everyday life at home, with two subcategories: The family, Work and
      School/preschool; 2. The influence of war on everyday life, with three
      subcategories: The war, The escape, Reflections; 3. The new life, with five
      subcategories: Employment, Health, Relatives and friends, Limited future,
      Transition to the new life. CONCLUSIONS: Health care and social welfare
      professionals need to find out what kind of lives refugee families have lived
      before coming to a new country, in order to determine individual needs of
      support. In this study the families had lived ordinary lives in their country of
      origin, and after experiencing a war situation they escaped to a new country and
      started a new life. They had thoughts of a limited future but also hopes of
      getting jobs and taking care of themselves and their families. When analysing
      each person's point of view one must seek an all-embracing picture of a family
      and its complexity to tie together the family narrative. To offer refugee
      families meetings with family-oriented professionals to provide the opportunity
      to create a family narrative is recommended for the health and social welfare
      sector. Using this knowledge by emphasizing the salutogenic perspectives
      facilitates support to refugee families and individuals. This kind of support can
      help refugee families to adapt to a new system of society and recapture a sense
      of coherence, including all three components that lead to coherence:
      comprehensibility, manageability and meaningfulness. More studies are needed to
      further investigate the thoughts, experiences and needs of various refugee
      families and how refugee receiving societies can give the most effective support.

PMID- 23537379
TI  - Age invariance in semantic and episodic metamemory: both younger and older adults
      provide accurate feeling-of-knowing for names of faces.
AB  - Age differences in feeling-of-knowing (FOK) accuracy were examined for both
      episodic memory and semantic memory. Younger and older adults either viewed
      pictures of famous faces (semantic memory) or associated non-famous faces and
      names (episodic memory) and were tested on their memory for the name of the
      presented face. Participants viewed the faces again and made a FOK prediction
      about future recognition of the name associated with the presented face. Finally,
      four-alternative forced-choice recognition memory for the name, cued by the face,
      was tested and confidence judgments (CJs) were collected for each recognition
      response. Age differences were not obtained in semantic memory or the resolution
      of semantic FOKs, defined by within-person correlations of FOKs with recognition
      memory performance. Although age differences were obtained in level of episodic
      memory, there were no age differences in the resolution of episodic FOKs. FOKs
      for correctly recognized items correlated reliably with CJs for both types of
      materials, and did not differ by age group. The results indicate age invariance
      in monitoring of retrieval processes for name-face associations.

PMID- 23537381
TI  - LiMn2O4 nanotube as cathode material of second-level charge capability for
      aqueous rechargeable batteries.
AB  - LiMn2O4 nanotube with a preferred orientation of (400) planes is prepared by
      using multiwall carbon nanotubes as a sacrificial template. Because of the
      nanostructure and preferred orientation, it shows a superfast second-level charge
      capability as a cathode for aqueous rechargeable lithium battery. At the charging
      rate of 600C (6 s), 53.9% capacity could be obtained. Its reversible capacity can
      be 110 mAh/g, and it also presents excellent cycling behavior due to the porous
      tube structure to buffer the strain and stress from Jahn-Teller effects.

PMID- 23537382
TI  - HONEY: a multimodality fall detection and telecare system.
AB  - BACKGROUND: The increasing cost in terms of money and healthcare resources is
      driving healthcare providers to provide home-based telecare instead of
      institutionalized healthcare. Falling is one of the most common and dangerous
      accidents for elderly individuals and a significant factor affecting the living
      quality of the elderly. Many efforts have been put toward providing a robust
      method to detect falls accurately and in a timely manner. This study facilitated
      a reliable, safe, and real-time home-based healthcare environment, which we have
      termed the Home Healthcare Sentinel System (HONEY), to detect falls for elderly
      people in the home telecare environment. The basic idea of HONEY is a three-step
      detection scheme that consists of multimodality signal sources, including an
      accelerometer sensor, audio, images, and video clips via speech recognition and
      on-demand video techniques. MATERIALS AND METHODS: The magnitude of acceleration,
      corresponding to a user's movements, triggers fall detection combining speech
      recognition and on-demand video. If a fall occurs, an alarm e-mail is delivered
      to medical staff or caregivers at once, containing the fall information, so that
      caregivers could make a primary diagnosis based on it. This article also
      describes the implementation of the prototype of HONEY. RESULTS: A comprehensive
      evaluation with 10 volunteers shows that HONEY has high accuracy of 94% for fall
      detection, 18% higher than the Advanced Magnitude Algorithm (AMA), which is a
      wearable sensor-based method, and the false-positive and false-negative rates are
      3% and 10%, respectively, 19% and 16% lower than AMA, respectively. The average
      response time for a detected fall is 46.2 s, which is also short enough for first
      aid. CONCLUSIONS: In summary, HONEY provides a highly reliable and convenient
      fall detection solution for the home-based environment.

PMID- 23537383
TI  - The U.S. Army Telemedicine and m-Health Program: making a difference at home and
      abroad.
AB  - This article highlights the deployment of telemedicine by the U.S. Army through
      the various echelons of care and in overseas locations, including range and scope
      of health services provided by telemedicine in a challenging environment. This is
      followed by a discussion of technological developments advances in mobile
      communications likely to change the practice of telemedicine in the military from
      limited fixed-point access to a highly mobile individual with handheld
      communication devices.

PMID- 23537384
TI  - How do hospital administrators perceive cardiac rehabilitation in a publicly
      funded health care system?
AB  - BACKGROUND: Patient and provider-related factors affecting access to cardiac
      rehabilitation (CR) have been extensively studied, but health-system
      administration factors have not. The objectives of this study were to investigate
      hospital administrators' (HA) awareness and knowledge of cardiac rehabilitation
      (CR), perceptions regarding resources for and benefit of CR, and attitudes toward
      and implementation of inpatient transition planning for outpatient CR. METHODS: A
      cross-sectional and observational design was used. A survey was administered to
      679 HAs through Canadian and Ontario databases. A descriptive examination was
      performed, and differences in HAs' perceptions by role, institution type and
      presence of within-institution CR were compared using t-tests. RESULTS: 195
      (28.7%) Canadian HAs completed the survey. Respondents reported good knowledge of
      what CR entails (mean=3.42+/-1.15/5). Awareness of the closest site was lower
      among HAs working in community versus academic institutions (3.88+/-1.24 vs.
      4.34+/-0.90/5 respectively; p=.01). HAs in non-executive roles (4.77+/-0.46/5)
      perceived greater CR importance for patients' care than executives (4.52+/-0.57;
      p=.001). HAs perceived CR programs should be situated in both hospitals and
      community settings (n=134, 71.7%). CONCLUSIONS: HAs value CR as part of patients'
      care, and are supportive of greater CR provision. Those working in community
      settings and executives may not be as aware of, or less-likely to value, CR
      services. CR leaders from academic institutions might consider liaising with
      community hospitals to raise awareness of CR benefits, and advocate for it with
      the executives in their home institutions.

PMID- 23537386
TI  - Teaching and learning about dementia in UK medical schools: a national survey.
AB  - BACKGROUND: Dementia is an increasingly common condition and all doctors, in both
      primary and secondary care environments, must be prepared to competently manage
      patients with this condition. It is unclear whether medical education about
      dementia is currently fit for purpose. This project surveys and evaluates the
      nature of teaching and learning about dementia for medical students in the UK.
      METHODS: Electronic questionnaire sent to UK medical schools. RESULTS: 23/31
      medical schools responded. All provided some dementia-specific teaching but this
      focussed more on knowledge and skills than behaviours and attitudes. Only 80% of
      schools described formal assessment of dementia-specific learning outcomes. There
      was a widespread failure to adequately engage the multidisciplinary team,
      patients and carers in teaching, presenting students with a narrow view of the
      condition. However, some innovative approaches were also highlighted.
      CONCLUSIONS: Although all schools taught about dementia, the deficiencies
      identified represent a failure to sufficiently equip medical students to care for
      patients with dementia which, given the prevalence of the condition, does not
      adequately prepare them for work as doctors. Recommendations for improving
      undergraduate medical education about dementia are outlined.

PMID- 23537387
TI  - Pathobiology and transmission of highly and low pathogenic avian influenza
      viruses in European quail (Coturnix c. coturnix).
AB  - European quail (Coturnix c. coturnix) may share with Japanese quail (Coturnix c.
      japonica) its potential as an intermediate host and reservoir of avian influenza
      viruses (AIV). To elucidate this question, European quail were experimentally
      challenged with two highly pathogenic AIV (HPAIV) (H7N1/HP and H5N1/HP) and one
      low pathogenic AIV (LPAIV) (H7N2/LP). Contact animals were also used to assess
      the viral transmission among birds. Severe neurological signs and mortality rates
      of 67% (H7N1/HP) and 92% (H5N1/HP) were observed. Although histopathological
      findings were present in both HPAIV-infected groups, H5N1/HP-quail displayed a
      broader viral antigen distribution and extent of microscopic lesions. Neither
      clinical nor pathological involvement was observed in LPAIV-infected quail.
      Consistent long-term viral shedding and effective transmission to naive quail was
      demonstrated for the three studied AIV. Drinking water arose as a possible
      transmission route and feathers as a potential origin of HPAIV dissemination. The
      present study demonstrates that European quail may play a major role in AI
      epidemiology, highlighting the need to further understand its putative role as an
      intermediate host for avian/mammalian reassortant viruses.

PMID- 23537388
TI  - Structural changes in cytochrome c oxidase induced by binding of sodium and
      calcium ions: an ATR-FTIR study.
AB  - Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy
      was used to investigate the binding of Na(+) and Ca(2+)cations to bovine
      cytochrome c oxidase in its fully oxidized and partially reduced, cyanide-ligated
      (a(2+)a3(3+)-CN) (mixed valence) forms. These ions induced distinctly different
      IR binding spectra, indicating that the induced structural changes are different.
      Despite this, their binding spectra were mutually exclusive, confirming their
      known competitive binding behavior. Dissociation constants for Na(+) and Ca(2+)
      with the oxidized enzyme were 1.2 mM and 11 MUM, respectively and Na(+) binding
      appeared to involve cooperative binding of two Na(+). Ca(2+) binding induced a
      large IR spectrum, with prominent amide I/II polypeptide changes, bandshifts
      assigned to carboxylate and an arginine, and a number of bandshifts of heme a.
      The Na(+)-induced binding spectrum showed much weaker amide I/II and heme a
      changes but had similar shifts assignable to carboxylate and arginine residues.
      Yeast CcO also displayed a calcium-induced IR and UV/visible binding spectra,
      though of lower intensities. This was attributed to the difficulty in fully
      depleting Ca(2+) from its binding site, as has been found with bacterial CcOs.
      The implications of Ca(2+)/Na(+) ion binding are discussed in terms of structure
      and possible modulation of core catalytic function.

PMID- 23537389
TI  - Investigating the relationship between predictability and imbalance in
      minimisation: a simulation study.
AB  - BACKGROUND: The use of restricted randomisation methods such as minimisation is
      increasing. This paper investigates under what conditions it is preferable to use
      restricted randomisation in order to achieve balance between treatment groups at
      baseline with regard to important prognostic factors and whether trialists should
      be concerned that minimisation may be considered deterministic. METHODS: Using
      minimisation as the randomisation algorithm, treatment allocation was simulated
      for hypothetical patients entering a theoretical study having values for
      prognostic factors randomly assigned with a stipulated probability. The number of
      times the allocation could have been determined with certainty and the imbalances
      which might occur following randomisation using minimisation were examined.
      RESULTS: Overall treatment balance is relatively unaffected by reducing the
      probability of allocation to optimal treatment group (P) but within-variable
      balance can be affected by any P <1. This effect is magnified by increased
      numbers of prognostic variables, the number of categories within them and the
      prevalence of these categories within the study population. CONCLUSIONS: In
      general, for smaller trials, probability of treatment allocation to the treatment
      group with fewer numbers requires a larger value P to keep treatment and variable
      groups balanced. For larger trials probability of allocation values from P = 0.5
      to P = 0.8 can be used while still maintaining balance. For one prognostic
      variable there is no significant benefit in terms of predictability in reducing
      the value of P. However, for more than one prognostic variable, significant
      reduction in levels of predictability can be achieved with the appropriate choice
      of P for the given trial design.

PMID- 23537390
TI  - The buccohypophyseal canal is an ancestral vertebrate trait maintained by
      modulation in sonic hedgehog signaling.
AB  - BACKGROUND: The pituitary gland is formed by the juxtaposition of two tissues:
      neuroectoderm arising from the basal diencephalon, and oral epithelium, which
      invaginates towards the central nervous system from the roof of the mouth. The
      oral invagination that reaches the brain from the mouth is referred to as
      Rathke's pouch, with the tip forming the adenohypophysis and the stalk
      disappearing after the earliest stages of development. In tetrapods, formation of
      the cranial base establishes a definitive barrier between the pituitary and oral
      cavity; however, numerous extinct and extant vertebrate species retain an open
      buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke's pouch.
      Little is currently known about the formation and function of this structure.
      Here we have investigated molecular mechanisms driving the formation of the
      buccohypophyseal canal and their evolutionary significance. RESULTS: We show that
      Rathke's pouch is located at a boundary region delineated by endoderm, neural
      crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1,
      R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray
      microtomography after iodine staining in mouse embryos, the pouch has a lobulated
      three-dimensional structure that embraces the descending diencephalon during
      pituitary formation. Polaris(fl/fl); Wnt1-Cre, Ofd1(-/-) and Kif3a(-/-) primary
      cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present
      with malformations of the anterior pituitary gland and midline structures of the
      anterior cranial base. Changes in the expressions of Shh downstream genes are
      confirmed in Gas1(-/-) mice. From an evolutionary perspective, persistence of the
      buccohypophyseal canal is a basal character for all vertebrates and its
      maintenance in several groups is related to a specific morphology of the midline
      that can be related to modulation in Shh signaling. CONCLUSION: These results
      provide insight into a poorly understood ancestral vertebrate structure. It
      appears that the opening of the buccohypophyseal canal depends upon Shh signaling
      and that modulation in this pathway most probably accounts for its persistence in
      phylogeny.

PMID- 23537392
TI  - Melanotan II overdose associated with priapism.

PMID- 23537391
TI  - A randomized, double-blind, placebo-controlled trial of oral montelukast in acute
      asthma exacerbation.
AB  - BACKGROUND: Leukotriene receptor antagonists (LTRAs) are well established in the
      management of outpatient asthma. However, there is very little information as to
      their role in acute asthma exacerbations. We hypothesized that LTRAs may
      accelerate lung function recovery when given in an acute exacerbation. METHODS: A
      randomized, double blind, placebo-controlled trial was conducted at the Aga Khan
      University Hospital to assess the efficacy of oral montelukast on patients of 16
      years of age and above who were hospitalized with acute asthma exacerbation. The
      patients were given either montelukast or placebo along with standard therapy
      throughout the hospital stay for acute asthma. Improvements in lung function and
      duration of hospital stay were monitored. RESULTS: 100 patients were randomized;
      their mean age was 52 years (SD +/- 18.50). The majority were females (79%) and
      non-smokers (89%). The mean hospital stay was 3.70 +/- 1.93 days with 80% of
      patients discharged in 3 days. There was no significant difference in clinical
      symptoms, PEF over the course of hospital stay (p = 0.20 at day 2 and p = 0.47 at
      day 3) and discharge (p = 0.15), FEV1 at discharge (p = 0.29) or length of
      hospital stay (p = 0.90) between the two groups. No serious adverse effects were
      noted during the course of the study. CONCLUSION: Our study suggests that there
      is no benefit of addition of oral montelukast over conventional treatment in the
      management of acute asthma attack. TRIAL REGISTRATION:  TRIAL REGISTRATION
      NUMBER: 375-Med/ERC-04.

PMID- 23537393
TI  - Mixed ligand Cu2+ complexes of a model therapeutic with Alzheimer's amyloid-beta
      peptide and monoamine neurotransmitters.
AB  - 8-Hydroxyquinolines (8HQ) have found widespread application in chemistry and
      biology due to their ability to complex a range of transition metal ions. The
      family of 2-substituted 8HQs has been proposed for use in the treatment of
      Alzheimer's disease (AD). Most notably, the therapeutic PBT2 (Prana Biotechnology
      Ltd.) has been shown to act as an efficient metal chaperone, disaggregate metal
      enriched amyloid plaques comprised of the Abeta peptide, inhibit Cu/Abeta redox
      chemistry, and reverse the AD phenotype in transgenic animal models. Yet
      surprisingly little is known about the molecular interactions at play. In this
      study, we show that the homologous ligand 2-[(dimethylamino)methyl]-8
      hydroxyquinoline (HL) forms a CuL complex with a conditional (apparent)
      dissociation constant of 0.33 nM at pH 6.9 and is capable of forming ternary
      Cu(2+) complexes with neurotransmitters including histamine (HA), glutamic acid
      (Glu), and glycine (Gly), with glutathione disulfide (GSSG), and with histidine
      (His) side chains of proteins and peptides including the Abeta peptide. Our
      findings suggest a molecular basis for the strong metal chaperone activity of
      PBT2, its ability to attenuate Cu(2+)/Abeta interactions, and its potential to
      promote neuroprotective and neuroregenerative effects.

PMID- 23537394
TI  - Importance of the ammonia assimilation by Penicillium purpurogenum in amino
      derivative Monascus pigment, PP-V, production.
AB  - A fungal strain, Penicillium purpurogenum IAM 15392, produced the azaphilone
      Monascus pigment homolog when cultured in a medium composed of soluble starch,
      ammonium nitrate, yeast extract, and citrate buffer, pH 5.0. One of the typical
      features of violet pigment PP-V [(10Z)-12- carboxyl-monascorubramine] is that
      pyranoid oxygen is replaced with nitrogen. In this study, we found that glutamine
      synthetase (glnB) and glutamate dehydrogenase (gdh1) genes were expressed in the
      culture conditions conducive to PP-V production. Gln and Glu both support PP-V
      biosynthesis, but PP-V biosynthesis was much more efficient with Gln. We
      determined that synthesis of Gln by glutamine synthetase from ammonium is
      important for PP-V production.

PMID- 23537395
TI  - Prevalence and pattern of vitreo-retinal diseases in Nepal: the Bhaktapur
      glaucoma study.
AB  - BACKGROUND: Vitreo-retinal diseases are among the leading causes of visual
      impairment and blindness worldwide. This study reports the prevalence and pattern
      of vitreo-retinal diseases in the Bhaktapur Glaucoma Study (BGS), a population
      based study conducted in Nepal. METHODS: BGS was a population based cross
      sectional study involving 4800 subjects aged 40 years and over from Bhaktapur
      district. Subjects were selected using a cluster sampling methodology and a door
      to-door enumeration. All subjects underwent a detailed ocular examination at the
      base hospital which included log MAR visual acuity, refraction, applanation
      tonometry and a dilated fundus examination. Fundus photography, optical coherence
      tomography and fundus fluorescein angiography were performed where indicated.
      RESULTS: Complete data was available for 3966 (82.62%) out of the total of 4800
      enumerated subjects. The mean age was 55.08 years (SD 11.51). The overall
      prevalence of vitreo-retinal disorders was 5.35% (95% CI, 4.67 - 6.09).
      Increasing age was associated with a higher prevalence of vitreo-retinal
      disorders (P < 0.001). The prevalence of diabetes mellitus was 7.69% (95% CI,
      6.88 - 8.56). Age-related macular degeneration (AMD) was the most common vitreo
      retinal disorder with a prevalence of 1.50% (95% CI, 1.15 - 1.94), increasing
      significantly with age. The prevalence of diabetic retinopathy among the study
      population was 0.78% (95% CI, 0.53 - 1.11) and among the diabetic population
      10.16% (95% CI, 7.01 - 14.12). The population prevalence of other retinal
      disorders were hypertensive retinopathy 0.88%, macular scar 0.37%, retinal vein
      occlusion 0.50%, macular hole 0.20%, retinitis pigmentosa 0.12%. and retinal
      detachment 0.10%.The prevalence of low vision and blindness due to vitreo-retinal
      disorders was 1.53% (95% CI, 1.18 - 1.97) and 0.65% (95% CI, 0.43 - 0.96),
      respectively. The prevalence of low vision and blindness was 28.77% (95% CI,
      22.78-35.37) and 12.26% (95% CI, 8.17-17.45), respectively among cases with
      vitreo-retinal disorders. Blindness was observed to be unilateral in 19 cases
      (73%), and bilateral in 7 cases (27%). CONCLUSIONS: The prevalence of vitreo
      retinal disorders in this Nepalese population was 5.35%, which increased
      significantly with age. AMD was the predominant retinal condition followed by
      diabetic retinopathy. One fourth of the subjects with vitreo-retinal disorder had
      low vision. Taking into consideration the aging population and emerging systemic
      diseases such as diabetes mellitus and hypertension, vitreo-retinal disorders
      could be of future public health importance.

PMID- 23537396
TI  - Synthesis and characterization of some novel fatty acid analogues: a preliminary
      investigation on their activity against human lung carcinoma cell line.
AB  - BACKGROUND: Preparation of some novel heterocyclic compounds with long alkyl and
      alkenyl chain of cytotoxic activity. METHODS: Gamma linolenic acid, a poly
      unsaturated fatty acid and stearic acid, a saturated fatty acid were isolated
      from the microalga Spirulina platensis. Some novel gamma linolenic acid and
      stearic acid analogues having 1,3,4-oxadiazole and 1,2,4-triazole were
      synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis.
      Cytotoxicity of these compounds was evaluated by the growth inhibition of A-549
      cells in-vitro. RESULTS: Compound 1 and 3 showed comparable cytotoxicity against
      the human lung carcinoma A-549 cell lines.

PMID- 23537397
TI  - Vaccination against herpes zoster and postherpetic neuralgia in France: a cost
      effectiveness analysis.
AB  - This study assesses the cost-effectiveness of vaccination against herpes zoster
      (HZ) and postherpetic neuralgia in France, using a published Markov model. The
      cost-effectiveness of vaccinating individuals aged from 65 years or between 70
      and 79 years was evaluated over their lifetime, from a third-party payer
      perspective. French-specific data were combined with results from clinical
      studies and international quality-of-life-based (EuroQol five-dimension
      questionnaire) utilities from the literature. HZ vaccination was highly cost
      effective in both populations. Incremental cost-effective ratios were estimated
      between ?9513 and 12,304 per quality-adjusted life year gained, corresponding to
      ?2240-2651 per HZ case avoided and ?3539-4395 per postherpetic neuralgia case
      avoided. In addition to epidemiological and clinical evidence, economic evidence
      also supports the implementation of HZ vaccination in France.

PMID- 23537398
TI  - Minor influence of sub-bowman keratomileusis on the posterior corneal surface at
      early stage.
AB  - PURPOSE: To evaluate the changes in posterior corneal surface (Q value and
      elevation) measured with Pentacam after femtosecond laser assisted Sub-Bowman
      Keratomileusis (SBK). METHODS: The Q values and elevation of posterior corneal
      surface were determined in 166 myopic/myopic astigmatism eyes of 88 patients
      using Scheimpflug imaging (Pentacam; Oculus, Wetzlar, Germany), which estimates
      asphericity and elevation for several areas of cornea analysed (Q value: 6, 7, 8
      and 9 mm; elevation: 2, 4, 6 and 8 mm) before 1 and 3 months after SBK. The
      correlations between the changes of Q value or elevation and the mean
      preoperative spherical equivalent (SE), central corneal thickness (CCT), central
      ablation depth (AD), estimated residual bed thickness (RBT) and RBT/CCT ratio
      were investigated. RESULTS: Meridian and area differences in Q of posterior
      surface have been showed. Two major meridians (horizontal/vertical) present the
      change of significant negative direction before surgery (all p < 0.001), but the
      alteration of significant positive direction for all post-SBK follow-up visits
      (all p < 0.05). There was no statistically significant difference in posterior
      elevation at 2 mm zone (horizontal meridian: p = 0.439; vertical meridian: p =
      0.233). Compared with preoperation, minor but significant forward displacements
      were found in posterior elevation at 4 and 6 mm areas of cornea analyzed
      (horizontal meridian: all p < 0.001; vertical meridian: p < 0.001, p = 0.024,
      respectively). However, posterior elevation in two meridians
      (horizontal/vertical) at 8 mm region was displayed significant backward shift (p
      = 0.001, p < 0.001, respectively). The Pearson correlation test showed no
      significant correlation between the changes in the Q values and elevation data in
      vast majority of areas of cornea analyzed and the SE, CCT, AD, RBT, and RBT/CCT
      ratio at 1 and 3 months after surgery (all p > 0.05). CONCLUSIONS: The posterior
      corneal surface showed central flattening and peripheral steepening at early
      stage post-SBK. To combine the asphericity with the elevation of the posterior
      corneal surface can overall and accurately understand the posterior corneal shape
      and its variations after refractive surgery.

PMID- 23537399
TI  - Cell death proteomics database: consolidating proteomics data on cell death.
AB  - Programmed cell death is a ubiquitous process of utmost importance for the
      development and maintenance of multicellular organisms. More than 10 different
      types of programmed cell death forms have been discovered. Several proteomics
      analyses have been performed to gain insight in proteins involved in the
      different forms of programmed cell death. To consolidate these studies, we have
      developed the cell death proteomics (CDP) database, which comprehends data from
      apoptosis, autophagy, cytotoxic granule-mediated cell death, excitotoxicity,
      mitotic catastrophe, paraptosis, pyroptosis, and Wallerian degeneration. The CDP
      database is available as a web-based database to compare protein identifications
      and quantitative information across different experimental setups. The proteomics
      data of 73 publications were integrated and unified with protein annotations from
      UniProt-KB and gene ontology (GO). Currently, more than 6,500 records of more
      than 3,700 proteins are included in the CDP. Comparing apoptosis and autophagy
      using overrepresentation analysis of GO terms, the majority of enriched processes
      were found in both, but also some clear differences were perceived. Furthermore,
      the analysis revealed differences and similarities of the proteome between
      autophagosomal and overall autophagy. The CDP database represents a useful tool
      to consolidate data from proteome analyses of programmed cell death and is
      available at http://celldeathproteomics.uio.no.

PMID- 23537401
TI  - Working hard: women's self-care practices in Ghana.
AB  - Women's health care providers have noted an increased infant mortality rate among
      Ghanaian immigrants. We conducted focus groups with 17 women in Ghana. We asked
      them how they maintained their health both before and during pregnancy. When
      discussing their health, women repeatedly described the conditions or context of
      their daily lives and the traditional practices that they used to stay healthy.
      Knowledge of women's lives, the health care system that they previously used, and
      their cultural practices can be utilized by health care providers to more fully
      assess their patients and design more culturally appropriate care for this group
      of women. 

PMID- 23537402
TI  - Doctors' emotion regulation and patient satisfaction: a social-functional
      perspective.
AB  - Emotion regulation has been identified as an important component of medical
      consultation but there is limited research on the topic. Two studies tested
      expected relationships between doctors' emotion regulation (ER) skills and
      patient satisfaction and quality of doctor-patient interaction, focusing in
      particular on the role patient perceptions' of doctors' emotion regulation skills
      play in these associations. Study 1 comprised 100 patients reporting on their
      perceptions of doctors' overall emotion regulation skills, communication quality
      and nonverbal immediacy, and their satisfaction with the care provided. Patients'
      perceptions of doctors' emotion regulation skills were associated with patient
      satisfaction and communication quality; patient perceptions of doctors' nonverbal
      immediacy partially mediated these relationships. Study 2 collected data from 30
      doctors who reported on their typical emotion regulation strategies of
      reappraisal and suppression and 139 of their patients who reported on
      satisfaction with the medical treatment and positive affect. As expected,
      doctors' self-reported reappraisal was positively associated with their patients'
      satisfaction and positive affect. Doctors' suppression was also positively
      associated with patient satisfaction, while patients' gender moderated these
      effects. The two studies empirically document proposed links between doctors'
      emotion regulation and patient satisfaction. Notably, the results underline the
      role of patients' perceptions of doctors' emotion regulation skills and emotion
      expressions for patient outcomes and are in line with functional models of
      emotion in social interaction. 

PMID- 23537403
TI  - Randomized trial of Legflow((r)) paclitaxel eluting balloon and stenting versus
      standard percutaneous transluminal angioplasty and stenting for the treatment of
      intermediate and long lesions of the superficial femoral artery (RAPID trial):
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Restenosis after percutaneous transluminal angioplasty (PTA) of the
      superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow
      up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia,
      and thus reduce restenosis. Recently, the Legflow((r)) paclitaxel-coated balloon
      (Cardionovum Sp.z.o.o., Warsaw, Poland) (LPEB) has been introduced. This balloon
      is covered with shellac, a Food and Drug Administration (FDA) approved natural
      resin, to obtain an equally distributed tissue concentration of paclitaxel. The
      RAPID trial is designed to assess restenosis after PTA using the Legflow balloon
      combined with nitinol stenting versus uncoated balloons with nitinol stenting in
      SFA lesions >5 cm. METHODS/DESIGN: A total of 176 adult patients with Rutherford
      class 2 to class 6 symptoms due to intermediate (5-15 cm) or long (>15 cm)
      atherosclerotic lesions in the SFA will be randomly allocated for treatment with
      LPEB with nitinol stenting or uncoated balloon angioplasty with stenting.
      Stenting will be performed using the Supera((r)) stent in both groups (IDEV
      Technologies Inc., Webster, TX). The primary endpoint is the absence of binary
      restenosis of the treated SFA segment. Secondary outcomes are target lesion
      revascularization (TLR), clinical and hemodynamic outcome, amputation rate,
      mortality rate, adverse events, and device-specific adverse events. Follow up
      consists of four visits in which ankle-brachial indices (ABI), toe pressure
      measurements, and duplex ultrasound (DUS) will be performed. Furthermore, a
      peripheral artery questionnaire (PAQ) will be completed by the patients at each
      follow-up. In the event that DUS reveals a symptomatic >50% restenosis, or a >75%
      asymptomatic restenosis, additional digital subtraction angiography will be
      performed with any necessary re-intervention. DISCUSSION: The RAPID trial is a
      multicenter randomized controlled patient blind trial that will provide evidence
      concerning whether the use of the Legflow paclitaxel/shellac coated balloons with
      nitinol stenting significantly reduces the frequency of restenosis in
      intermediate and long SFA lesions compared to standard PTA and stenting. TRIAL
      REGISTRATION: ISRCTN47846578.

PMID- 23537404
TI  - Colonization of Anopheles cracens: a malaria vector of emerging importance.
AB  - BACKGROUND: Anopheles cracens has been incriminated as a vector for the simian
      malaria parasite, Plasmodium knowlesi, that is the fifth Plasmodium species
      infecting humans. Little experimental data exists on this mosquito species due to
      the lack of its availability in laboratories. FINDINGS: The population of An.
      cracens, collected from Kuala Lipis, Pahang was maintained at the insectary of
      the Department of Parasitology, Faculty of Medicine, University Malaya at 24-26
      degrees C and 60-80% relative humidity. The mosquitoes were maintained with
      artificial mating and blood-fed on humans and hamsters. The colony has been
      established since November 2011 and to date has reached its sixth generation.
      CONCLUSION: This is the first description of maintaining the Malaysian strain An.
      cracens colony by artificial mating. Colonization of An. cracens will provide
      fundamental information for genetic studies and will be useful in assessing
      comparative susceptibility to Plasmodium parasites.

PMID- 23537405
TI  - Ultrafast infrared spectroscopy on channelrhodopsin-2 reveals efficient energy
      transfer from the retinal chromophore to the protein.
AB  - The primary reaction dynamics of channelrhodopsin-2 was investigated using
      femtosecond vis-pump/mid-IR probe spectroscopy. Due to the fast deactivation of
      the excited state in channelrhodopsin-2, it is possible to observe the direct
      impact of retinal isomerization on the protein surrounding. We show that the
      dominant negative band at 1665 cm(-1) tentatively assigned to an amide I
      vibration is developed with a time constant of 0.5 ps. Also a variety of side
      chain vibrations are formed or intensified on this time scale. The comparison of
      the light-induced FT-IR spectra of channelrhodopsin-2 in H2O and D2O at 80 K
      enabled us to tentatively identify the contribution of Arg side chain(s). The
      subsequently observed decay of nearly the whole difference pattern has a
      particularly high impact on the C?C and C?N stretching vibrations of the retinal.
      This suggests that the underlying mechanism describes a cooling process in which
      the excess energy is redirected toward the retinal surrounding, e.g., the protein
      and functional water molecules. The pronounced protein contributions in
      comparison to other rhodopsins point to a very efficient energy redistribution in
      channelrhodopsin-2.

PMID- 23537406
TI  - Rhodium(III)-catalyzed direct selective C(5)-H oxidative annulations of 2
      substituted imidazoles and alkynes by double C-H activation.
AB  - Double C-H activations of C(5)-H and Csp(2)-H of 2-substituted N-vinyl- or
      arylimidazoles were realized without heteroatom-directing assistance by
      rhodium(III) catalyst. A subsequent oxidative annulation reaction with alkynes
      efficiently produced aza-fused heterocycles with high molecular complexity in low
      to excellent yields.

PMID- 23537408
TI  - [The PICC line, a new approach for venous access].
AB  - Peripheral Inserted Central Catheter (PICC) line is a peripherally inserted
      central catheter. This implantable medical device is placed into a peripheral
      vein of the arm in order to obtain an intravenous central access. This device can
      find its use in various applications like intravenous delivery of parenteral
      nutrition, anticancer agents and antibiotics, as well as for blood sampling. PICC
      line is not widely used in medical practice because it remains largely unknown.
      The aim of this review is thus to introduce PICC line to the medical and
      scientific community. First, we will approach its insertion and maintenance of
      the dressing. We will then detail the benefits and drawbacks associated with its
      use, and finally discuss its position with regards to the other central venous
      access available.

PMID- 23537407
TI  - Changes in transcriptome of native nasal epithelium expressing F508del-CFTR and
      intersecting data from comparable studies.
AB  - BACKGROUND: Microarray studies related to cystic fibrosis (CF) airway gene
      expression have gone some way in clarifying the complex molecular background of
      CF lung diseases, but have made little progress in defining a robust "molecular
      signature" associated with mutant CFTR expression. Disparate methodological and
      statistical analyses complicate comparisons between independent studies of the CF
      transcriptome, and although each study may be valid in isolation, the conclusions
      reached differ widely. METHODS: We carried out a small-scale whole genome
      microarray study of gene expression in human native nasal epithelial cells from
      F508del-CFTR homozygotes in comparison to non-CF controls. We performed
      superficial comparisons with other microarray datasets in an attempt to identify
      a subset of regulated genes that could act as a signature of F508del-CFTR
      expression in native airway tissue samples. RESULTS: Among the alterations
      detected in CF, up-regulation of genes involved in cell proliferation, and down
      regulation of cilia genes were the most notable. Other changes involved gene
      expression changes in calcium and membrane pathways, inflammation, defence
      response, wound healing and the involvement of estrogen signalling. Comparison of
      our data set with previously published studies allowed us to assess the
      consistency of independent microarray data sets, and shed light on the
      limitations of such snapshot studies in measuring a system as subtle and dynamic
      as the transcriptome. Comparison of in-vivo studies nevertheless yielded a small
      molecular CF signature worthy of future investigation. CONCLUSIONS: Despite the
      variability among the independent studies, the current CF transcriptome meta
      analysis identified subsets of differentially expressed genes in native airway
      tissues which provide both interesting clues to CF pathogenesis and a possible CF
      biomarker.

PMID- 23537409
TI  - [Which future in cardiovascular therapy for nitric oxide and its derivatives?].
AB  - Nitric oxide (NO) is involved in the regulation of several physiological
      processes such as vascular homeostasis. Exogenous NO supply offers major
      therapeutic interest, especially in the treatment of coronary artery disease,
      ischemic syndromes and other cardiovascular pathologies. Nevertheless, the
      administration of NO itself is limited by its short half-life. NO prodrugs have
      been marketed for decades, e.g. organic nitrates for angina pectoris. These
      prodrugs display undeniable advantages such as angina crisis relief and
      preconditioning effect. Nevertheless, they suffer from several drawbacks:
      toxicity, tolerance, endothelial dysfunction exacerbation. These negative effects
      are related to massive production of reactive species derived from oxygen or
      nitrogen, which trigger oxidative and nitrosative stress. New NO donors are under
      development to overcome those disadvantages, among which the S-nitrosothiols
      family seems especially promising.

PMID- 23537410
TI  - [Four new drugs on the market: abiraterone, belatacept, vandetanib and
      fidaxomycine].
AB  - Among the 35 new molecular entities approved by the FDA in 2011, 17 were
      particularly notable for their significant contributions to the health of
      patients, including abiraterone acetate, vandetanib, belatacept and fidaxomicin.
      Thus, abiraterone acetate, namely Zytiga(r), was included as the first in a new
      class of drugs to treat late-stage prostate cancer. The ability of Zytiga(r) to
      prolong survival in these patients was considered as significant because they
      have few other treatments options and the benefits of Zytiga(r) outweighed the
      risks of reported side-effects. Vandetanib, namely Caprelsa(r), was also
      considered as a relevant drug since it represents the first drug approved to
      treat particularly aggressive medullary thyroid cancer, an orphan disease.
      Despite huge progress in transplantation, renal transplantation remains a serious
      problem since patients treated with the calcineurin inhibitors cyclosporine and
      tacrolimus are at high risk of developing renal injury. With longer follow-up,
      the novel immunosuppressant belatacept continued to show better renal function
      compared with a cyclosporine-based regimen, as well as a consistent safety
      profile and comparable efficacy. It was approved by the Food and Drug
      Administration in June 2011 for the prophylaxis of organ rejection in adult
      recipients of a kidney transplant acting by a selective T-cell costimulation
      blocker given as an infusion. Clostridium difficile is currently the most
      important cause of infectious diarrhea in the United States. Fidaxomicin, a
      macrolide antibiotic, was recently approved for treatment of these infections
      (CDIs). It could be an alternative treatment for infection with C. difficile,
      with similar efficacy and safety to vancomycin. Fidaxomicin has minimal activity
      against Bacteroides species, which may be advantageous in maintaining
      colonization resistance and protecting the gastrointestinal tract from
      colonization by C. difficile.

PMID- 23537411
TI  - [Introduction to novel vaccine adjuvants and their role in influenza
      vaccination].
AB  - New vaccine approaches based on subunit vaccines and on highly purified
      recombinant proteins use adjuvants to compensate for the loss of
      immunostimulatory components that are naturally present in whole cell vaccines.
      The development of adjuvanted influenza vaccines comprising squalene emulsion
      adjuvants effective against pandemic influenza strains highlights the
      contribution of novel adjuvants in increasing vaccine coverage by augmenting
      protection rates and by affording cross-strain protection and antigen dose
      sparing. Nevertheless, the development of new adjuvants remains challenging in
      terms of quality and safety assurance and in terms of clinical and industrial
      development costs.

PMID- 23537412
TI  - [Mucopenetrating nanoparticles: vehicles for the oral administration of
      paclitaxel].
AB  - Paclitaxel is an anticancer drug used as solution for perfusion for the treatment
      of certain types of cancers. In the last years, a number of strategies have been
      proposed for the development of an oral formulation of this drug. However, this
      task is quite complicated due to the poor aqueous solubility of paclitaxel as
      well as the fact that this compound is substrate of the intestinal P-glycoprotein
      and the cytochrome P450 enzymatic complex. In this work, we have developed
      pegylated nanoparticles with mucopenetrating properties in order to conduct
      paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a
      size of about 180 nm and a drug loading close to 15% by weight. The
      pharmacokinetic study in mice has shown that these nanoparticles were capable to
      offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the
      oral relative bioavailability of paclitaxel when loaded in nanoparticles
      pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a
      subcutaneous model of tumour in mice, these pegylated nanoparticles administered
      orally every 3 days have demonstrated a similar efficacy than Taxol(r)
      administered intravenously every day during 9 days. All of these results
      suggested that these pegylated nanoparticles were capable to cross the mucus
      layer of the gut and, then, reach the surface of the enterocytes. The PEG
      molecules would facilitate the adhesion of nanoparticles to this epithelial
      surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote
      its absorption.

PMID- 23537413
TI  - [Meloxicam-induced colitis revealed by acute abdominal pain].
AB  - Whether intestinal toxicity of preferential or selective COX-2 inhibitors is
      reduced compared with that of standard NSAIDs is controversial. A 26-year-old
      woman presented with acute abdominal pain and bloody diarrhoea a few days after
      beginning meloxicam treatment. Endoscopic examination of the colon showed
      erythematous and ulcerative lesions involving 15 cm of the left colon. No
      aetiology has been found for colitis. Diarrhea disappeared 1 week after meloxicam
      was stopped. Total colonoscopy 3 months and 2 years later was normal. The role of
      meloxicam in the etiology of colitis was considered plausible. This report and a
      few other cases in the literature suggest that cyclooxygenase-2 selective non
      steroidal anti-inflammatory drug inhibitor toxicity should be investigated in
      case of unexplained acute colitis.

PMID- 23537414
TI  - [Assessment of pharmaceutical databases available in France].
AB  - OBJECTIVE: To assess the relevance of several pharmaceutical databases (PDBs) to
      be integrated in a computerized prescription system for hospitals. MATERIALS AND
      METHODS: Fifty medical prescriptions were designed as tests. They were supposed
      to answer to a security or a relevance assessment item. They were analyzed using
      four French PDBs (Claude-Bernard, Theriaque, Thesorimed, Vidal), available
      online. The outcome was the rate of conformity with the expected answers.
      RESULTS: The rate of conformity was: 31% for Claude-Bernard, 30% for Theriaque,
      26% for Vidal, and 20% for Thesorimed (no statistical significance). DISCUSSION:
      The PDBs easily detect interactions between different pharmacological class drugs
      but redundancies and illogical situations are poorly intercepted. They seem to
      manage medicines only by the active ingredient, irrespective of the dose or the
      indication. The knowledge of the patient profile and the context are not really
      enriched by the content of the prescription. CONCLUSION: The efficacy of these
      PDB has to be improved.

PMID- 23537415
TI  - [How can we evaluate medication adherence? What are the methods?].
AB  - INTRODUCTION: Identifying the difficulties of the patient towards following his
      medication regimen remains complex for the healthcare provider. This can be
      explained by the multidimensional character of medication adherence and,
      actually, the evaluation of this phenomenon. The objective of this work was to
      review the various methods to measure medication adherence. METHODS: We performed
      a search on PubMed completed by a manual one. RESULTS: Two types of measure are
      described. The "direct" methods are based on the measurement of the level of
      medicine or metabolite in blood or urine, measurement of biologic markers in
      blood or measurement of physiologic or clinical markers. The "indirect" methods
      are represented by the analysis of the administrative databases (prescription,
      rate of prescription refills); pill counts; electronic medication monitors; the
      self-reported measures by the patient or his close relations (questionnaires,
      diaries, interviews); the opinion of the healthcare provider. DISCUSSION: None of
      these tools supplants the others, each having limits either of feasibility, or
      reliability. In the end, it is the crossing of the information stemming from
      these various equipments that allows an idea on the adherence behavior of the
      patient and especially, dimensions on which he is most in trouble. CONCLUSION:
      The identification of these difficulties can allow the healthcare provider to
      develop behavioral and organizational skills tailored to the patient follow-up.

PMID- 23537416
TI  - Factors associated with suboptimal adherence to antiretroviral therapy in Viet
      Nam: a cross-sectional study using audio computer-assisted self-interview
      (ACASI).
AB  - BACKGROUND: Optimal adherence to antiretroviral therapy (ART) is necessary for
      people living with HIV/AIDS (PLHIV). There have been relatively few systematic
      analyses of factors that promote or inhibit adherence to antiretroviral therapy
      among PLHIV in Asia. This study assessed ART adherence and examined factors
      associated with suboptimal adherence in northern Viet Nam. METHODS: Data from 615
      PLHIV on ART in two urban and three rural outpatient clinics were collected by
      medical record extraction and from patient interviews using audio computer
      assisted self-interview (ACASI). RESULTS: The prevalence of suboptimal adherence
      was estimated to be 24.9% via a visual analogue scale (VAS) of past-month dose
      missing and 29.1% using a modified Adult AIDS Clinical Trial Group scale for on
      time dose-taking in the past 4 days. Factors significantly associated with the
      more conservative VAS score were: depression (p < 0.001), side-effect experiences
      (p < 0.001), heavy alcohol use (p = 0.001), chance health locus of control (p =
      0.003), low perceived quality of information from care providers (p = 0.04) and
      low social connectedness (p = 0.03). Illicit drug use alone was not significantly
      associated with suboptimal adherence, but interacted with heavy alcohol use to
      reduce adherence (p < 0.001). CONCLUSIONS: This is the largest survey of ART
      adherence yet reported from Asia and the first in a developing country to use the
      ACASI method in this context. The evidence strongly indicates that ART services
      in Viet Nam should include screening and treatment for depression, linkage with
      alcohol and/or drug dependence treatment, and counselling to address the belief
      that chance or luck determines health outcomes.

PMID- 23537417
TI  - Experiences of continuous subcutaneous insulin infusion in pregnant women with
      type 1 diabetes during delivery from four Italian centers: a retrospective
      observational study.
AB  - OBJECTIVES: An optimized metabolic control during delivery is mandatory to
      prevent maternal-neonatal complications. The primary aim of this study was to
      evaluate the efficacy and safety of continuous subcutaneous insulin infusion
      (CSII) during delivery in pregnant women with type 1 diabetes. The secondary aim
      was to assess the impact of real-time continuous glucose monitoring (RT-CGM)
      added to CSII versus CSII alone. RESEARCH DESIGN AND METHODS: This was a
      multicenter observational retrospective study. A standardized protocol, to use
      CSII throughout pregnancy and delivery, foresaw three different insulin basal
      rates according to blood glucose level: profile A, the last basal rate in use;
      profile B, preventive 50% reduction of the last basal rate in use; and profile C,
      0.1-0.2 U/h for blood glucose level <70 mg/dL, activated just before anesthesia
      or at the beginning of active labor. An alternative intravenous protocol (IVP)
      was given in case of complications and relevant metabolic deterioration. Blood
      glucose in the target range (70-140 mg/dL) throughout delivery and percentage of
      activation of the IVP were primary outcomes. RESULTS: Sixty-five pregnant women
      with diabetes included in the study (56-86% cesarean section; 9-14%
      spontaneous/stimulated vaginal delivery). Mean blood glucose level was 102 +/- 31
      mg/dL at 0 min, 109 +/- 42 mg/dL at 30 min, 120 +/- 48 mg/dL at 60 min, and 99 +/
      34 mg/dL at 24 h. Mean basal rate during delivery was 0.6 +/- 0.4 U/h (profile
      B). Mean capillary blood glucose (CBG) level was lower in the RT-CGM group
      relative to the CSII-alone group: 80 +/- 14 mg/dL versus 111 +/- 32 mg/dL at 0
      min (P<0.01), 79 +/- 11 mg/dL versus 109 +/- 42 mg/dL at 30 min (P<0.02), and 98
      +/- 20 mg/dL versus 125 +/- 51 mg/dL at 60 min (difference not significant).
      Eleven newborns experienced transient neonatal hypoglycemia. None of the women
      switched to IVP. No major differences were observed according to delivery
      procedure. CONCLUSIONS: CSII is possible and safe in different types of delivery
      in selected and educated women. RT-CGM helps to obtain better outcomes in terms
      of maternal peripartum CBG level.

PMID- 23537418
TI  - Insulin pump-long-term effects on glycemic control: an observational study at 10
      diabetes clinics in Sweden.
AB  - AIM: This study examined long-term effects of continuous subcutaneous insulin
      infusion (CSII) in clinical practice on glycemic control in patients with type 1
      diabetes. SUBJECTS AND METHODS: We evaluated all type 1 diabetes patients at 10
      diabetes outpatient clinics in Sweden who had been treated with CSII for at least
      5.5 years and had valid glycated hemoglobin (HbA1c) data before starting pump use
      and at 5 years +/- 6 months. Controls treated with multiple daily insulin
      injections (MDI) over a time-matched period were also evaluated. RESULTS: There
      were 331 patients treated with CSII at least 5.5 years at the 10 clinics. Of
      these, 272 (82%) fulfilled the inclusion criteria. Patients treated with CSII
      were younger than those treated with MDI (mean age, 38.6 vs. 45.6 years;
      P<0.001), more were women (56% vs. 43%; P<0.001), and diabetes duration was
      shorter (mean, 15.1 years vs. 20.1 years; P<0.001). After adjusting for variables
      differing at baseline and influencing the change in HbA1c over the study period,
      the reduction in HbA1c remained statistically significant at 5 years and was
      estimated to be 0.20% (95% confidence interval [CI] 0.07-0.32) (2.17 mmol/mol
      [95% CI 0.81-3.53]) (P=0.002). The corresponding adjusted reduction at years 1
      and 2 was 0.42% (95% CI 0.31-0.53) (4.59 mmol/mol [95% CI 3.41-5.77]) (P<0.001)
      and 0.43% (95% CI 0.31-0.55) (4.71 mmol/mol [95% CI 3.38-6.04]) (P<0.001),
      respectively. The effect of insulin pump use versus controls on HbA1c decreased
      significantly with time (P<0.001). CONCLUSIONS: Use of CSII in clinical practice
      in Sweden is associated with an approximately 0.2% (2 mmol/mol) reduction in
      HbA1c after 5 years.

PMID- 23537419
TI  - Impact of remote management of diabetes via computer: the 360 study--a proof-of
      concept randomized trial.
AB  - BACKGROUND: Previous studies have provided limited guidance regarding the
      clinical efficacy and cost-effectiveness of interventions using "telemedicine"
      models in the management of diabetes mellitus. We conducted a study to determine
      if routine clinical assessments of diabetes patients could be effectively
      conducted via computer and telephone interaction with patients and still provide
      clinical results similar to traditional office care. SUBJECTS AND METHODS: We
      enrolled 100 subjects with diabetes in this 12-month, randomized, controlled, non
      inferiority study. Subjects were randomized (1:1 ratio) to a control group (CG)
      or study group (SG). Baseline characteristics were similar. CG subjects
      participated in quarterly office visits; SG subjects participated in two office
      visits (months 6 and 12) and two telemedicine interactions (months 3 and 9).
      Changes in clinical measurements (hemoglobin A1c [HbA1c], blood pressure, lipids,
      body mass index [BMI], and body weight) and clinician time requirements were
      assessed. RESULTS: Seventy subjects completed the study (CG, n=37; SG, n=33). No
      significant between-group differences in HbA1c, blood pressure, lipids, or BMI
      were seen at 12 months. SG subjects showed significantly greater reductions in
      mean (SD) body weight compared with CG subjects: -5.2 (1.6) pounds versus -0.7
      (1.5) pounds, respectively (P=0.04). Clinician time requirements for SG subjects
      were reduced by >40%. CONCLUSIONS: Our study demonstrated that use of a
      telemedicine-based treatment protocol in diabetes patients is feasible and
      efficient and yields similar clinical outcomes compared with traditional, clinic
      based protocols. Telemedicine applications of computer software can potentially
      expand access to care for patients and may reduce costs for patients, providers,
      and payers.

PMID- 23537420
TI  - Nocturnal continuous glucose monitoring: accuracy and reliability of hypoglycemia
      detection in patients with type 1 diabetes at high risk of severe hypoglycemia.
AB  - BACKGROUND: A reliable method to detect biochemical nocturnal hypoglycemia is
      highly needed, especially in patients with recurrent severe hypoglycemia. We
      evaluated reliability of nocturnal continuous glucose monitoring (CGM) in
      patients with type 1 diabetes at high risk of severe hypoglycemia. PATIENTS AND
      METHODS: Seventy-two type 1 diabetes patients with recurrent severe hypoglycemia
      (two or more events within the last year) participated for 4 nights in blinded
      CGM recordings (Guardian((r)) REAL-Time CGMS and Sof-Sensor((r)); Medtronic
      MiniMed, Northridge, CA). Blood was drawn hourly from 23:00 to 07:00 h for plasma
      glucose (PG) measurements (gold standard). RESULTS: Valid data were obtained in
      217 nights. The sensitivity of CGM was 65% (95% confidence interval, 53-77%)
      below 4 mmol/L, 40% (24-56%) below 3 mmol/L, and 17% (0-47%) below 2.2 mmol/L. PG
      and CGM readings correlated in the total measurement range (Spearman's rho=0.82;
      P<0.001). In the normo- and hyperglycemic ranges CGM underestimated PG by 1.1
      mmol/L (0.9-1.2 mmol/L) (P<0.001); in contrast, in the hypoglycemic range (PG<4
      mmol/L) CGM overestimated PG levels by 1.0 mmol/L (P<0.001). The mean absolute
      relative differences in the hypo- (<=3.9 mmol/L), normo- (4-9.9 mmol/L), and
      hyperglycemic (>=10 mmol/L) ranges were 45% (37-53%), 23% (22-25%), and 20% (19
      21%), respectively. Continuous glucose error grid analysis indicated a clinical
      accuracy of 56%, 99%, and 93% in the hypo-, normo-, and hyperglycemic ranges,
      respectively. CONCLUSIONS: The accuracy in the hypoglycemic range of nocturnal
      CGM data using Sof-Sensor is suboptimal in type 1 diabetes patients at high risk
      of severe hypoglycemia. To ensure clinical useful sensitivity in detection of
      nocturnal hypoglycemic episodes, an alarm threshold should not be lower than 4
      mmol/L.

PMID- 23537421
TI  - Confounding and missing data in cost-effectiveness analysis: comparing different
      methods.
AB  - INTRODUCTION: Common approaches in cost-effectiveness analyses do not adjust for
      confounders. In nonrandomized studies this can result in biased results.
      Parametric models such as regression models are commonly applied to adjust for
      confounding, but there are several issues which need to be accounted for. The
      distribution of costs is often skewed and there can be a considerable proportion
      of observations of zero costs, which cannot be well handled using simple linear
      models. Associations between costs and effectiveness cannot usually be explained
      using observed background information alone, which also requires special
      attention in parametric modeling. Furthermore, in longitudinal panel data,
      missing observations are a growing problem also with nonparametric methods when
      cumulative outcome measures are used. METHODS: We compare two methods, which can
      handle the aforementioned issues, in addition to the standard unadjusted
      bootstrap techniques for assessing cost-effectiveness in the Helsinki
      Psychotherapy Study based on five repeated measurements of the Global Severity
      Index (SCL-90-GSI) and direct costs during one year of follow-up in two groups
      defined by the Defence Style Questionnaire (DSQ) at baseline. The first method
      models cumulative costs and effectiveness using generalized linear models,
      multiple imputation and bootstrap techniques. The second method deals with
      repeated measurement data directly using a hierarchical two-part logistic and
      gamma regression model for costs, a hierarchical linear model for effectiveness,
      and Bayesian inference. RESULTS: The adjustment for confounders mitigated the
      differences of the DSQ groups. Our method, based on Bayesian inference, revealed
      the unexplained association of costs and effectiveness. Furthermore, the method
      also demonstrated strong heteroscedasticity in positive costs. CONCLUSIONS:
      Confounders should be accounted for in cost-effectiveness analyses, if the
      comparison groups are not randomized. JEL CLASSIFICATION: C1; C3; I1.

PMID- 23537422
TI  - Hand function in children with radial longitudinal deficiency.
AB  - BACKGROUND: In children with hypoplasia or aplasia of the radius (radial
      longitudinal deficiency) manual activity limitations may be caused by several
      factors; a short and bowed forearm, radial deviation of the wrist, a non
      functional or absent thumb, limited range of motion in the fingers and impaired
      grip strength. The present study investigates the relation between these
      variables and activity and participation in children with radial dysplasia.
      METHODS: Twenty children, age 4-17 years, with radial longitudinal dysplasia
      Bayne type II-IV were examined with focus on the International Classification of
      Functioning and Health, version for Children and Youth (ICF-CY) context. Body
      function/structure was evaluated by measures of range of motion, grip strength,
      sensibility and radiographic parameters. Activity was examined by Box and Block
      Test and Assisting Hand Assessment (AHA). Participation was assessed by
      Children's Hand-use Experience Questionnaire (CHEQ). Statistical correlations
      between assessments of body function/structure and activity as well as
      participation were examined. RESULTS: The mean total active motion of wrist (49.6
      degrees ) and digits (447 degrees ) were less than norms. The mean hand forearm
      angle was 34 degrees  radially. Ulnar length ranged from 40 to 80% of age-related
      norms. Grip strength (mean 2.7 kg) and Box and Block Test (mean 33.8
      blocks/minute) were considerably lower than for age-related norms. The mean score
      for the AHA was 55.9 and for CHEQ Grasp efficiency 69.3. The AHA had significant
      relationship with the total range of motion of digits (p = 0.042). Self
      experienced time of performance (CHEQ Time) had significant relationship with
      total active motion of wrist (p = 0.043). Hand forearm angle did not show any
      significant relationship with Box and Block Test, AHA or CHEQ. CONCLUSION: In
      radial longitudinal deficiency total range of motion of digits and wrist may be
      of more cardinal importance to the child's activity and participation than the
      angulation of the wrist.

PMID- 23537423
TI  - Quality of life among parents of children with phenylketonuria (PKU).
AB  - BACKGROUND: Parents of children with chronic conditions are known to be at risk
      of impairment in their quality of life (QoL). Studies considering other chronic
      conditions proposed diverse factors to have an impact on the parent's QoL. So
      far, there has been little research on parents who have a child with
      phenylketonuria (PKU). This study was designed to evaluate the parental quality
      of life (PQoL) of parents of children and adolescents who have PKU and identify
      possible predictors of PQoL. METHODS: In this cross-sectional study 89 parents
      completed self-report measures of PQoL, family stress, social support, and
      parental coping. To determine the impact of these potential predictors on PQoL,
      regression and mediation analyses were performed. RESULTS: Most parents coped
      well with their children's metabolic disorder. Family stress (beta = -0.42; p <
      0.001) and perceived social support (beta = 0.33; p = 0.001) were proven to be
      the most powerful predictors, accounting together for 45% of the variance of
      PQoL. Social support mediated the association between family stress and PQoL.
      CONCLUSIONS: The current study indicates that parents of younger children are an
      especially vulnerable group. Members of health-care teams should be able to
      identify and empower vulnerable parents to seek and maintain social support.

PMID- 23537424
TI  - Pressure-dependent reversible increase in T(c) for the ferrimagnetic 2-D
      Mn(II)(TCNE)I(OH2) and 3-D Mn(II)(TCNE)(3/2)(I3)(1/2).zTHF organic-based magnets.
AB  - The pressure dependence of the magnetic properties of ferrimagnetic
      Mn(II)(TCNE)I(OH2) up to 14.05 kbar and Mn(II)(TCNE)(3/2)(I3)(1/2).zTHF up to
      14.32 kbar were studied. For Mn(II)(TCNE)I(OH2), two distinct pressure regions
      separated at ~1 kbar were evident in both the temperature and the field-dependent
      magnetic measurements. No increase of the magnetic properties was observed in the
      low-pressure region, while significant increases to the magnetic ordering
      temperature, T(c), bifurcation temperature, T(b), coercive field, H(cr), and
      remnant magnetization, M(r), were evident in the high-pressure region. The T(c),
      T(b), H(cr), M(r), and M(5 T) reversibly increased from ambient pressure values
      of 169 K, 169 K, 690 Oe, 620 emuOe/mol, and 13,800 emuOe/mol to 257 K, 261 K,
      1460 Oe, 2300 emuOe/mol, and 17,100 emuOe/mol at 14.05 kbar, respectively. For
      Mn(II)(TCNE)(3/2)(I3)(1/2).zTHF, the T(c) and T(b) were nearly coincident and
      increased linearly from 173 and 173 K, respectively, at ambient pressure to 273
      and 272 K, respectively, at 14.32 kbar. Thus, the T(c) increased at an average
      rate of 6.25 and 7.18 K/kbar for Mn(II)(TCNE)I(OH2) and
      Mn(II)(TCNE)(3/2)(I3)(1/2).zTHF, respectively. For Mn(TCNE)(1/2)(I3)(1/2).zTHF
      remnant magnetization and saturation magnetization did not significantly change
      with applied pressure. The H(cr) exhibited a linear increase from ambient
      pressure to 5.00 kbar, reaching 860 Oe, but only achieving 880 Oe at 14.32 kbar.

PMID- 23537426
TI  - Integrating economic parameters into genetic selection for Large White pigs.
AB  - The objective of the study was to integrate economic parameters into genetic
      selection for sow productivity, growth performance and carcass characteristics in
      South African Large White pigs. Simulation models for sow productivity and
      terminal production systems were performed based on a hypothetical 100-sow herd,
      to derive economic values for the economically relevant traits. The traits
      included in the study were number born alive (NBA), 21-day litter size (D21LS),
      21-day litter weight (D21LWT), average daily gain (ADG), feed conversion ratio
      (FCR), age at slaughter (AGES), dressing percentage (DRESS), lean content (LEAN)
      and backfat thickness (BFAT). Growth of a pig was described by the Gompertz
      growth function, while feed intake was derived from the nutrient requirements of
      pigs at the respective ages. Partial budgeting and partial differentiation of the
      profit function were used to derive economic values, which were defined as the
      change in profit per unit genetic change in a given trait. The respective
      economic values (ZAR) were: 61.26, 38.02, 210.15, 33.34, -21.81, -68.18, 5.78,
      4.69 and -1.48. These economic values indicated the direction and emphases of
      selection, and were sensitive to changes in feed prices and marketing prices for
      carcasses and maiden gilts. Economic values for NBA, D21LS, DRESS and LEAN
      decreased with increasing feed prices, suggesting a point where genetic
      improvement would be a loss, if feed prices continued to increase. The economic
      values for DRESS and LEAN increased as the marketing prices for carcasses
      increased, while the economic value for BFAT was not sensitive to changes in all
      prices. Reductions in economic values can be counterbalanced by simultaneous
      increases in marketing prices of carcasses and maiden gilts. Economic values
      facilitate genetic improvement by translating it to proportionate profitability.
      Breeders should, however, continually recalculate economic values to place the
      most appropriate emphases on the respective traits during genetic selection. 

PMID- 23537427
TI  - Measurements of rate constants for the OH reactions with bromoform (CHBr3),
      CHBr2Cl, CHBrCl2, and epichlorohydrin (C3H5ClO).
AB  - Measurements of the rate constants for the gas phase reactions of OH radicals
      with bromoform (CHBr3) and epichlorohydrin (C3H5ClO) were performed using a flash
      photolysis resonance-fluorescence technique over the temperature range 230-370 K.
      The temperature dependences of the rate constants can be represented by the
      following expressions: kBF(230-370 K) = (9.94 +/- 0.76) * 10(-13) exp[-(387 +/-
      22)/T] cm(3) molecule(-1) s(-1) and kECH(230-370 K) = 1.05 * 10(-14)(T/298)(5.16)
      exp(+1082/T) cm(3) molecule(-1) s(-1). Rate constants for the reactions of OH
      with CHCl2Br and CHClBr2 were measured between 230 and 330 K. They can be
      represented by the following expressions: kDCBM(230-330 K) = (9.4 +/- 1.3) * 10(
      13) exp[-(513 +/- 37)/T] cm(3) molecule(-1) s(-1) and kCDBM(230-330 K) = (9.0 +/-
      1.9) * 10(-13) exp[-(423 +/- 61)/T] cm(3) molecule(-1) s(-1). The atmospheric
      lifetimes due to reactions with tropospheric OH were estimated to be 57, 39, 72,
      and 96 days, respectively. The total atmospheric lifetimes of the Br-containing
      methanes due to both reaction with OH and photolysis were calculated to be 22,
      50, and 67 days for CHBr3, CHClBr2, and CHCl2Br, respectively. 

PMID- 23537428
TI  - Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of
      its metabolites against cancer cell lines.
AB  - BACKGROUND: Microbial transformation of steroids has been extensively used for
      the synthesis of steroidal drugs, that often yield novel analogues, not easy to
      obtain by chemical synthesis. We report here fungal transformation of a synthetic
      steroidal drug, exemestane, used for the treatment of breast cancer and function
      through inhibition of aromatase enzyme. RESULTS: Microbial transformation of anti
      cancer steroid, exemestane (1), was investigated by using two filamentous fungi.
      Incubation of 1 with fungi Macrophomina phaseolina, and Fusarium lini afforded
      three new, 11alpha-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2),
      16beta, 17beta-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), and 17beta
      hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and one known
      metabolites, 17beta-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5). Their
      structures were deduced spectroscopically. Compared to 1 (steroidal aromatase
      inactivator), the transformed metabolites were also evaluated for cytotoxic
      activity by using a cell viability assay against cancer cell lines (HeLa and
      PC3). Metabolite 2 was found to be moderately active against both the cell lines.
      CONCLUSIONS: Biotransformation of exemestane (1) provides an efficient method for
      the synthesis of new analogues of 1. The metabolites were obtained as a result of
      reduction of double bond and hydroxylation. The transformed product 2 exhibited a
      moderate activity against cancer cell lines (HeLa and PC3). These transformed
      products can be studied for their potential as drug candidates.

PMID- 23537430
TI  - Sitagliptin pretreatment in diabetes patients presenting with acute coronary
      syndrome: results from the Acute Coronary Syndrome Israeli Survey (ACSIS).
AB  - BACKGROUND: Chronic treatment with currently available oral hypoglyemic
      medications may result in a differential effect on the clinical presentation of
      diabetic patients with acute coronary syndrome (ACS). METHODS: We evaluated
      presentation characteristics and the risk for in-hospital complications and 30
      day major adverse cardiovascular events (MACE) among 445 patients with diabetes
      mellitus enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) 2010.
      Patients were categorized into 3 groups according to glucose lowering medications
      at time of admission for ACS: 1) DPP 4 inhibitors (as monotherapy or in
      combination; DPP4i), 2) Metformin (monotherapy or in combination, excluding
      DPP4i) and 3) other oral hypoglycemics. RESULTS: Patients in the DPP4i group
      displayed similar baseline clinical characteristics to the other 2 groups, with
      the exception of a younger age and a lower frequency of prior coronary heart
      disease and chronic renal failure. Medical therapy with DPP4i was associated with
      a significantly lower in-hospital complication rate (post MI angina, re
      infarction, pulmonary edema, infections, acute renal failure and better KILLIP
      class) (9.7%), lower rates of 30-day MACE (12.9%) and a shorter hospital stay
      (5.4 +/- 3.8 days) as compared with patients treated with metformin (24.4%, 31.6%
      and 5.6 +/- 5.0 days respectively) or other oral hypoglycemic drugs (45.5%, 48.5%
      and 7.5 +/- 6.5 days respectively). Consistently, multivariate logistic
      regression modeling revealed that treatment with DPP4i was associated with a
      lower risk for in-hospital complications (OR = 0.129, p = 0.002) and 30-day MACE
      (OR = 0.157, p = 0.002) compared with other oral hypoglycaemic therapy.
      CONCLUSIONS: Our data suggests that chronic treatment with DPP4i may have
      cardioprotective effects in diabetes patients presenting with acute coronary
      syndrome.

PMID- 23537431
TI  - Cytokine patterns associated with a serotype 8 fowl adenovirus infection.
AB  - This study examined cytokine gene expression patterns associated with fowl
      adenovirus (FAdV) infection. The selected cytokine mRNA was quantified by
      quantitative real-time reverse transcription-PCR in spleen, liver, and cecal
      tonsil during the course of infection of chickens with a serotype 8 FAdV (FAdV
      8). Compared to uninfected chickens, infected birds had higher mRNA expression of
      interleukin (IL)-18 and IL-10 in spleen and liver, respectively. Interferon gamma
      (IFN-gamma) mRNA expressed in spleen and liver of infected chickens was
      significantly upregulated, while the expression of IL-8 mRNA in spleen and liver
      of infected chickens was significantly downregulated. There was no significant
      difference between infected and uninfected groups in terms of cytokine gene
      expression in cecal tonsil. These results indicate that these four cytokines
      might play an important role in driving the immune responses following FAdV-8
      infection.

PMID- 23537432
TI  - Why fruits are rich in antioxidants? An opinion review.
AB  - We rarely consider whether and how plants benefit from making antioxidant-rich
      fruits, despite our dependence on fruits as routine sources of these compounds.
      The hypothesis presented here is that storage of the antioxidant materials is
      advantageous to the survival of the plant species. This hypothesis is based on
      the premise that at different stages from flower bud opening to seedling
      formation, the concentrations of the reactive oxygen species (ROS) needed vary
      tremendously. Exposing seeds of several plant species to ROS aids germination.
      However, ROS can cause considerable damage by mutagenesis during plant
      embryogenesis. It is suggested that the antioxidant-rich environment in fruits
      protects the developing plant embryos from this damage. It also allows for an
      antioxidant environment for packaging the embryos into seeds with tight seed
      coats. After fruit maturation and seed dispersal, a prolonged exposure to oxygen
      and moisture enables the seeds to produce the ROS needed for seed germination.
      There is a simultaneous increase in the ROS scavenging systems to allow for
      protection of the dividing cells afterwards. These observations are unified into
      the hypothesis that the antioxidant rich fruits aid in the survival of plant
      species, and discussed in the context of vascular plant evolution.

PMID- 23537433
TI  - Oxidative stress and cardiovascular health: therapeutic potential of polyphenols.
AB  - Reactive oxygen species (ROS) are important in normal cellular function and
      physiology. However, oxidative stress resulting from an accumulation of ROS has a
      detrimental impact on cellular function, and ROS has been implicated in the
      pathogenesis of a number of diseases, including cardiovascular diseases. This
      review provides a summary of the impact of ROS on cardiovascular health and
      diseases, highlighting the therapeutic use of antioxidants. In addition, this
      review summarizes the health benefits of polyphenols, and the recent progress on
      understanding the cellular and physiological actions by which polyphenols may
      impart their beneficial properties on cardiovascular health.

PMID- 23537434
TI  - Oxidative-stress-induced epigenetic changes in chronic diabetic complications.
AB  - Oxidative stress plays an important role in the development and progression of
      chronic diabetic complications. Diabetes causes mitochondrial superoxide
      overproduction in the endothelial cells of both large and small vessels. This
      increased superoxide production causes the activation of several signal pathways
      involved in the pathogenesis of chronic complications. In particular, endothelial
      cells are major targets of glucose-induced oxidative damage in the target organs.
      Oxidative stress activates cellular signaling pathways and transcription factors
      in endothelial cells including protein kinase C (PKC), c-Jun-N-terminal kinase
      (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and
      nuclear factor kappa-B (NF-kappaB). Oxidative stress also causes DNA damage and
      activates DNA nucleotide excision repair enzymes including the excision repair
      cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP).
      Augmented production of histone acetyltransferase p300, and alterations of
      histone deacetylases, including class III deacetylases sirtuins, are also
      involved in this process. Recent research has found that small noncoding RNAs,
      like microRNA, are a new kind of regulator associated with chronic diabetic
      complications. There are extensive and complicated interactions and among these
      molecules. The purpose of this review is to demonstrate the role of oxidative
      stress in the development of diabetic complications in relation to epigenetic
      changes such as acetylation and microRNA alterations.

PMID- 23537435
TI  - Role of epidermal growth factor receptor transactivation in endothelin-1-induced
      enhanced expression of Gi protein and proliferation in A10 vascular smooth muscle
      cells.
AB  - We have recently shown that vasoactive peptides such as angiotensin II (Ang II)
      and endothelin-1 (ET-1) increase the expression of Gi proteins and the
      proliferation of A10 vascular smooth muscle cells (VSMC) through mitogen
      activated protein (MAP) kinase-phosphoinositide (PI) 3-kinase pathways. This
      study was intended to examine the implication of epidermal growth factor receptor
      (EGFR) activation in ET-1-induced enhanced expression of Gi proteins and
      proliferation of A10 VSMC, and to further investigate the underlying mechanisms
      responsible for these increases. Cell proliferation was determined by
      [(3)H]thymidine incorporation and the expression of Gi proteins; extracellular
      signal-regulated kinases 1 and 2 (ERK1/2) and EGFR phosphorylation was determined
      by Western blotting. Treatment of A10 VSMC with ET-1 enhanced the expression of
      Gi proteins, which was attenuated by BQ123 and BQ788, antagonists of ET(A) and
      ET(B) receptor respectively. In addition, ET-1 enhanced the phosphorylation of
      EGFR in A10 VSMC, which was restored to the control levels by EGFR inhibitor and
      ETA and ETB receptor antagonists. Furthermore, ET-1 also augmented the
      proliferation and ERK1/2 phosphorylation of A10 VSMC, which were restored to the
      control levels by inhibition of EGFR. These data suggest that ET-1 transactivates
      EGFR, which, through MAP kinase signaling, may contribute to the enhanced
      expression of Gi proteins and thus increased proliferation of A10 VSMC.

PMID- 23537436
TI  - The interaction of diamines and polyamines with the peroxidase-catalyzed
      metabolism of aromatic amines: a potential mechanism for the modulation of
      aniline toxicity.
AB  - Synthetic and biological amines such as ethylenediamine (EDA), spermine, and
      spermidine have not been previously investigated in free-radical biochemical
      systems involving aniline-based drugs or xenobiotics. We aimed to study the
      influence of polyamines in the modulation of aromatic amine radical metabolites
      in peroxidase-mediated free radical reactions. The aniline compounds tested
      caused a relatively low oxidation rate of glutathione in the presence of
      horseradish peroxidase (HRP), and H2O2; however, they demonstrated marked oxygen
      consumption when a polyamine molecule was present. Next, we characterized the
      free-radical products generated by these reactions using spin-trapping and
      electron paramagnetic resonance (EPR) spectrometry. Primary and secondary but not
      tertiary polyamines dose-dependently enhanced the N-centered radicals of
      different aniline compounds catalyzed by either HRP or myeloperoxidase, which we
      believe occurred via charge transfer intermediates and subsequent stabilization
      of aniline-derived radical species as suggested by isotopically labeled aniline.
      Aniline/peroxidase reaction product(s) were monitored at 435 nm by kinetic
      spectrophotometry in the presence and absence of a polyamine additive. Using gas
      chromatography-mass spectrometry, the dimerziation product of aniline,
      azobenzene, was significantly amplified when EDA was present. In conclusion, di-
      and poly-amines are capable of enhancing the formation of aromatic-amine-derived
      free radicals, a fact that is expected to have toxicological consequences.

PMID- 23537437
TI  - Modeling xenobiotic susceptibility to hepatotoxicity using an in vitro oxidative
      stress inflammation model.
AB  - Evidence suggests xenobiotic exposure during periods of inflammation can increase
      an individual's susceptibility to toxicity. The present study aimed to validate
      an in-vitro inflammatory model to identify compounds that increase hepatotoxicity
      during inflammation. Using freshly isolated hepatocytes exposed to a low nontoxic
      flow of H2O2 using glucose (G) and glucose oxidase (GO) and supplementing it with
      either peroxidase or Fe(II), the effects of inflammation on 2 classes of drugs
      known to cause hepatotoxicity were examined: nitroaromatics (nimesulide,
      nilutamide, flutamide) and aromatic amines (clozapine, thioridazine). Co
      incubation with G/GO and the nitroaromatics increased toxicity that was further
      increased when peroxidase was present. While the aromatic amines did not increase
      cytotoxicity with G/GO alone, they demonstrated significant increases in
      cytotoxicity when incubated with peroxidase+G/GO. Liver injury is commonly
      observed with alcohol abusers; therefore, the effects of inflammation on ethanol,
      and its metabolite acetaldehyde, were observed. Both ethanol and acetaldehyde
      increased cytotoxicity, which was further increased when Fe(II) was present.
      These results implicate H2O2, a cellular mediator of inflammation, as a potential
      risk factor for hepatotoxicity. A H2O2-enhanced hepatocyte-system in the presence
      of peroxidase or Fe(II) may prove useful for a more robust screening of
      xenobiotics for assessing potential toxicity associated with inflammation.

PMID- 23537438
TI  - Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is
      inhibited by curcumin in A-10 vascular smooth muscle cells.
AB  - Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the
      signaling pathways responsible for inducing hypertrophic and proliferative
      responses in vascular smooth muscle cells (VSMC). We have previously demonstrated
      that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and
      proliferative responses of angiotensin II (Ang-II) and endothelin-1 (ET-1).
      Curcumin, a polyphenolic compound derived from the spice turmeric is known to
      possess antiproliferative properties and exerts vasculoprotective effects.
      However, the ability of curcumin to modulate IGF-1-induced signaling responses in
      VSMC remains to be investigated. In this study, we determined the effect of
      curcumin on IGF-1-induced phosphorylation of protein kinase B (PKB), glycogen
      synthase kinase-3beta (GSK-3beta), and IGF-1R in VSMC. Curcumin inhibited IGF-1
      induced phosphorylation of PKB and GSK-3beta as well as the IGF-1R beta subunit
      in a dose-dependent fashion. In addition, IGF-1-induced expression of early
      growth response protein 1 (Egr-1) which plays a pathogenic role in vascular
      dysfunctions, was also attenuated by curcumin. In conclusion, these results
      indicate that curcumin is a potent inhibitor of key components of the IGF-1
      induced mitogenic and proliferative signaling system in VSMC, and suggest that
      curcumin-induced attenuation of these signaling components may constitute a
      potential mechanism for its vasculoprotective effects.

PMID- 23537439
TI  - The antioxidant resveratrol down-regulates inflammation in an in-vitro model of
      Pseudomonas aeruginosa infection of lung epithelial cells.
AB  - Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that can cause
      severe pulmonary infection in immunocompromized individuals. During the
      infectious process, P. aeruginosa provokes a potent inflammatory response and
      induces the release of reactive oxygen species (ROS). Cells undergo oxidative
      stress when cellular antioxidants are unable to effectively scavenge and detoxify
      ROS, resulting in lung damage. Resveratrol (3,5,4'-trihydroxystilbene) is a
      natural polyphenolic compound with recognized antioxidant effects. We
      hypothesized that owing to its antioxidant activities, resveratrol can attenuate
      an inflammatory response in P. aeruginosa-infected cells. Lung epithelial A549
      cells were pre-treated with 100 MUmol/L of resveratrol for 5 h, followed by
      infection with P. aeruginosa. Intracellular ROS generation was used as an
      indicator of P. aeruginosa-induced oxidative stress, and cell surface expression
      of Fas receptor and activation of caspases-3 and -7 as indicators of apoptosis.
      We also measured the surface expression of intercellular adhesion molecule (ICAM)
      1 and enzymes related to inflammation and redox signaling. Resveratrol
      significantly reduced ROS generation, ICAM-1, and human beta-defensin-2
      expression, as well as the markers of apoptosis in A549 cells infected with P.
      aeruginosa, and up-regulated glutathione peroxidase, suggesting its potential
      therapeutic role in protecting the lungs against the deleterious effects of P.
      aeruginosa infection.

PMID- 23537442
TI  - Benchmarking changes in symptom intensity and magnitude of disability.

PMID- 23537443
TI  - The carpal insertions of the transverse carpal ligament.
AB  - PURPOSE: To quantitatively define the anatomic insertions of the transverse
      carpal ligament (TCL) to the carpals. METHODS: We dissected 5 fresh-frozen
      cadaver limbs, isolating the TCL. The ligament insertion sites into bone were
      clearly marked and photographed. We then used computer software to measure the
      area of insertion into the individual carpals. RESULTS: The TCL had consistent
      insertion sites into the scaphoid, trapezium, pisiform, and hamate. The average
      insertion of the TCL on the scaphoid was 6 * 6 mm (proximal to distal * radial to
      ulnar maximum distance), trapezium 13 * 6 mm, pisiform 9 * 6 mm, and hamate 11 *
      5 mm. The area of ligament insertion on the scaphoid was 29 mm(2), trapezium was
      42 mm(2), pisiform was 38 mm(2), and hamate was 40 mm(2). The perimeter of the
      ligament insertion on the scaphoid was 21 mm, trapezium was 28 mm, pisiform was
      25 mm, and hamate was 29 mm. CONCLUSIONS: The TCL has a broad but definable
      footprint on the trapezium and scaphoid on the radial side and the hamate and the
      pisiform on the ulnar side of the carpal tunnel. The distal carpal insertion
      sites are longer and oblong, whereas the proximal insertion sites are more
      circular. CLINICAL RELEVANCE: Precise knowledge of TCL attachment sites may allow
      the surgeon greater confidence and safety during procedures that involve its
      release, such as carpal tunnel release, trapeziectomy, hook of hamate excision,
      or Guyon canal release.

PMID- 23537444
TI  - Radioscapholunate arthrodesis with compression screws and local autograft.
AB  - Radioscapholunate arthrodesis is performed for patients who experience pain and
      disability from radiocarpal arthritis. Initial reports from the 1980s
      demonstrated high nonunion rates and marginal clinical outcomes. Improvements in
      surgical technique and clearly defined indications have reduced nonunion rates
      and improved patient satisfaction. We present a technique using headless
      compression screws inserted through a dorsal approach, which optimizes hardware
      placement and incorporates local bone graft harvested from the insertion site to
      supplement the arthrodesis.

PMID- 23537445
TI  - In reply.

PMID- 23537446
TI  - Letter regarding "The Krukenberg procedure".

PMID- 23537447
TI  - A Serbian version of modified and revised Experiences in Close Relationships
      scale (SM-ECR-R).
AB  - We present details about the validation of the Serbian version of the Experiences
      in Close Relationships-Revised questionnaire modified to measure attachment in
      close relationships in general (SM-ECR-R). Its psychometric features were
      examined with 2 samples of students (N = 719 and N = 91) and 1 group of employed
      adults (N = 259). The results obtained in the student sample were equivalent to
      those obtained in validation studies worldwide, whereas in the more heterogeneous
      sample of employed adults, internal consistency of both avoidance and anxiety was
      lower and their intercorrelation was higher. Test-retest reliability was
      satisfactory, and relations with measures of attachment, empathy, and personality
      structure were meaningful. The results support the SM-ECR-R as a reliable and
      valid research instrument, but its internal structure and consistency might vary
      in different samples, depending on age, education, gender, and culture. 

PMID- 23537448
TI  - Preface disc degeneration for The Spine Journal.

PMID- 23537449
TI  - Commentary: Thoracolumbar spine fractures: is more knowledge better?
AB  - COMMENTARY ON: Verlaan J-J, Dhert WJA, Oner FC. Intervertebral disc viability
      after burst fractures of the thoracic and lumbar spine treated with pedicle screw
      fixation and direct end-plate restoration. Spine J 2013;13:217-21 (in this
      issue).

PMID- 23537450
TI  - Ionizing radiation exposure and the development of intervertebral disc
      degeneration--no case to answer.
AB  - In the following perspective article, Mellor and Breen provide a counterpoint to
      a previous perspective on the potential link between ionizing radiation exposure
      and intervertebral disc degeneration in humans [1]. The previous perspective
      asked, is this link a myth or reality? It suggested the potential for such a
      link. Mellor and Breen offer a drastically alternate view, in essence, that the
      question itself is flawed. To support their perspective, they explain the
      different units of radiation measurement and their conversion to risk in humans
      and how this impacts the previous perspective. They explain the variable
      sensitivity of different body tissues to radiation and highlight that neither
      human research nor any of the multiple international regulatory agencies have
      ever suggested that the intervertebral disc is sensitive to radiation. Finally,
      they claim that it is impossible to predict with any certainty the effects of low
      level radiation on the intervertebral discs.

PMID- 23537451
TI  - Samartzis et al. respond.

PMID- 23537452
TI  - The effects of simulated microgravity on intervertebral disc degeneration.
AB  - BACKGROUND CONTEXT: Astronauts experience back pain, particularly low back pain,
      during and after spaceflight. Recent studies have described histologic and
      biochemical changes in rat intervertebral discs after space travel, but there is
      still no in vitro model to investigate the effects of microgravity on disc
      metabolism. PURPOSE: To study the effects of microgravity on disc degeneration
      and establish an in vitro simulated microgravity study model. STUDY DESIGN: Discs
      were cultured in static and rotating conditions in bioreactor, and the
      characteristics of disc degeneration were evaluated. METHODS: The mice discs were
      cultured in a rotating wall vessel bioreactor where the microgravity condition
      was simulated. Intervertebral discs were cultured in static and microgravity
      condition. Histology, biochemistry, and immunohistochemical assays were performed
      to evaluate the characteristics of the discs in microgravity condition. RESULTS:
      Intervertebral discs cultured in rotating bioreactors were found to develop
      changes of disc degeneration manifested by reduced red Safranin-O staining within
      the annulus fibrosus, downregulated glycosaminoglycan (GAG) content and
      GAG/hydroxyproline ratio, increased matrix metalloproteinase 3 expression, and
      upregulated apoptosis. CONCLUSIONS: We conclude that simulated microgravity
      induces the molecular changes of disc degeneration. The rotating bioreactor model
      will provide a foundation to investigate the effects of microgravity on disc
      metabolism.

PMID- 23537454
TI  - The molecular basis of intervertebral disc degeneration.
AB  - BACKGROUND: Intervertebral disc (IVD) degeneration remains a clinically important
      condition for which treatment is costly and relatively ineffective. The molecular
      basis of degenerative disc disease has been an intense focus of research
      recently, which has greatly increased our understanding of the biology underlying
      this process. PURPOSE: To review the current understanding of the molecular basis
      of disc degeneration. STUDY DESIGN: Review article. METHODS: A literature review
      was performed to identify recent investigations and current knowledge regarding
      the molecular basis of IVD degeneration. RESULTS: The unique structural
      requirements and biochemical properties of the disc contribute to its propensity
      toward degeneration. Mounting evidence suggests that genetic factors account for
      up to 75% of individual susceptibility to IVD degeneration, far more than the
      environmental factors such as occupational exposure or smoking that were
      previously suspected to figure prominently in this process. Decreased
      extracellular matrix production, increased production of degradative enzymes, and
      increased expression of inflammatory cytokines contribute to the loss of
      structural integrity and accelerate IVD degeneration. Neurovascular ingrowth
      occurs, in part, because of the changing degenerative phenotype. CONCLUSIONS: A
      detailed understanding of the biology of IVD degeneration is essential to the
      design of therapeutic solutions to treat degenerative discs. Although significant
      advances have been made in explaining the biologic mediators of disc
      degeneration, the inhospitable biochemical environment of the IVD remains a
      challenging environment for biological therapies.

PMID- 23537455
TI  - The role of cross sectional imaging in the management of acute pyogenic inguinal
      abscess - extrapelvic versus intrapelvic origin.
AB  - BACKGROUND: Abscesses involving the inguinal region as manifestations of complex
      soft-tissue infections are rare, and the infectious route is usually unclear. The
      purpose of this study was to ascertain the importance of imaging study and
      whether the clinical presentations differ between the extrapelvic and intrapelvic
      origin. METHODS: Patients who presented with inguinal abscess between January
      2003 and December 2010 were evaluated retrospectively. All patients received
      broad-spectrum antibiotic therapy and debridement. Imaging studies, including
      computed tomography or magnetic resonance imaging, were performed in all patients
      to elucidate the origin and extent of infectious disease, and the results were
      reviewed. Clinical data, laboratory examination findings, and culture results
      were analyzed. RESULTS: Twenty-eight patients were enrolled in the study: 13
      patients whose infections were of extrapelvic origin (Group 1) and 15 patients of
      intrapelvic origin (Group 2). Imaging studies yielded information that helped
      guiding the treatment. Gram-positive coccus infection was more frequent in Group
      1 (p < 0.001), while mixed pathogen and anaerobic bacterial infection were more
      frequent in Group 2 (p = 0.002 and p = 0.006, respectively). Group 2 had a higher
      incidence of history of malignancy and chronic renal failure (p = 0.044 and p =
      0.038, respectively). CONCLUSIONS: Computed tomography and magnetic resonance
      imaging are helpful in diagnosing cases of inguinal abscess and determining the
      extent of infection. In patients presenting with acute pyogenic inguinal abscess,
      a higher prevalence of chronic renal failure and history of malignancy were found
      in those with an intrapelvic, as compared with an extrapelvic, origin of
      infection.

PMID- 23537453
TI  - Genetic polymorphisms associated with intervertebral disc degeneration.
AB  - BACKGROUND CONTEXT: Disc degeneration (DD) is a multifaceted chronic process that
      alters the structure and function of the intervertebral discs and can lead to
      painful conditions. The pathophysiology of degeneration is not well understood,
      but previous studies suggest that certain genetic polymorphisms may be important
      contributing factors leading to an increased risk of DD. PURPOSE: To review the
      genetic factors in DD with a focus on polymorphisms and their putative role in
      the pathophysiology of degeneration. Elucidating the genetic components that are
      associated with degeneration could provide insights into the mechanism of the
      process. Furthermore, defining these relationships and eventually using them in a
      clinical setting may allow an identification and early intervention for those who
      are at a high risk for painful DD. STUDY DESIGN: Literature review. METHODS: This
      literature review focused on the studies concerning genetic polymorphisms and
      their associations with DD. RESULTS: Genetic polymorphisms in 20 genes have been
      analyzed in association with DD, including vitamin D receptor, growth
      differentiation factor 5 (GDF5), aggrecan, collagen Types I, IX, and XI,
      fibronectin, hyaluronan and proteoglycan link protein 1 (HAPLN1), thrombospondin,
      cartilage intermediate layer protein (CILP), asporin, MMP1, 2, and 3, parkinson
      protein 2, E3 ubiquitin protein ligase (PARK2), proteosome subunit beta type 9
      (PSMB9), tissue inhibitor of metalloproteinase (TIMP), cyclooxygenase-2 (COX2),
      and IL1alpha, IL1beta, and IL6. Each genetic polymorphism codes for a protein
      that has a functional role in the pathogenesis of DD. CONCLUSIONS: There are
      known associations between several genetic polymorphisms and DD. Of the 20 genes
      analyzed, polymorphisms in vitamin D receptor, aggrecan, Type IX collagen,
      asporin, MMP3, IL1, and IL6 show the most promise as functional variants. Genetic
      studies are crucial for understanding the mechanism of the degeneration. This
      genetic information could eventually be used as a predictive model for
      determining a patient's risk for symptomatic DD.

PMID- 23537456
TI  - Assessment of the effectiveness of pharmacotherapy follow-up in patients treated
      for depression.
AB  - BACKGROUND: Several studies have established the effectiveness of pharmaceutical
      care (PC) in patients with heart failure, diabetes, hypertension, and
      dyslipidemia. However, there are few studies using standardized methods, e.g.,
      randomized controlled trials, to assess the effectiveness of pharmacotherapy
      follow-up (PF) in patients with depression. OBJECTIVE: To assess the
      effectiveness of PC via PF according to the Dader Method in female patients
      diagnosed with depression. METHODS: Sixty-eight patients were selected and
      randomly allocated to groups, stratified by age, type of medication, severity of
      depression, and presence of recurrence and/or relapse. Patients in the
      intervention group (IG) received clinical pharmacy intervention at monthly visits
      over a 3-month follow-up period. The control group (CG) also received monthly
      visits from the pharmacist, but PF intervention was not performed. RESULTS: A
      comparison of the effects of usual treatment (CG) and PC (IG) on depressive
      symptoms showed a statistically significant difference between groups, with a
      median reduction in Beck Depression Inventory score (Delta) of 2.5 points in the
      CG and 13.5 points in the IG. Similarly, statistically significant results were
      observed for anxiety symptoms, with a median reduction in Beck Anxiety Inventory
      score (Delta) of 3.5 points in the CG and 13.0 points in the IG. The patients who
      underwent PF showed a high level of satisfaction with the service. CONCLUSION:
      The PF is well accepted and effective in treating depressed patients, as
      indicated by the reduction of the depressive and anxious symptoms.

PMID- 23537457
TI  - Impact of a patient-centered pharmacy program and intervention in a high-risk
      group.
AB  - BACKGROUND: The medication therapy management (MTM) program identified high-risk
      members in a large employer group and invited them to participate in an MTM
      program. The intervention consisted of at least 3 consultations with a clinical
      pharmacist to review and discuss drug therapy. The goal was to improve drug
      therapy adherence and clinical outcomes. OBJECTIVE: To assess the impact of MTM
      on plan-paid health care costs, utilization of medical services, overall days
      supply of targeted medications, and medication possession ratios (MPRs). METHODS:
      The MTM and control group comprised eligible members of a large employer
      prescription benefit plan who were identified between October 1, 2007, and
      November 12, 2008, and invited to participate. Control group members were
      selected from targeted members who declined. After propensity score matching to
      ensure similarity of groups at baseline, each group had 2,250 members. Baseline
      comparisons and post-period impact analyses between groups were conducted using
      bivariate analysis. Post-period analyses used tests for paired comparisons. The
      MTM and control group members were studied for the year before and after their
      individual program invitations. We measured pre-post differences between the MTM
      members and controls in total heath care costs, inpatient visits, emergency room
      (ER) visits, total days supply, and MPRs for 5 conditions: diabetes,
      hypertension, dyslipidemia, depression, and asthma. RESULTS: MTM members
      significantly reduced their plan-paid health care costs by 10.3% or $977,
      compared with an increase of 0.7% or $62 in the control group (P = 0.048).
      Inpatient visits in the MTM group decreased by 18.6%, while the control group
      experienced an increase of 24.2% (P  less than  0.001). While both groups had
      decreases in ER visits, the groups were not significantly different (P = 0.399).
      Average days supply for the MTM group increased by 72.7 days over baseline; for
      the control group, it decreased by 111.1 days (P  less than  0.001). MTM members
      with hypertension and dyslipidemia had pre-post increases in MPR of 2.29% and
      2.10%, respectively, while the control group had decreases of 2.31% and 2.61%
      (both P  less than  0.001). The mean MPRs for members with diabetes, depression,
      and asthma did not change in either group. Program costs per patient in 2009 were
      estimated to be $478. The program had a return on investment (ROI) of 2.0 in
      2009. CONCLUSIONS: This study found that the pharmacist-managed MTM program to
      reconcile the medication therapies of high-risk patients and improve adherence,
      as measured by MPR, was effective in reducing total health care costs. The
      results show that those patients in the intervention group with hypertension and
      dyslipidemia had significant improvements in medication adherence, as compared
      with the control group. In fact, the intervention group used significantly more
      days of therapy in the intervention period, and the control group used
      significantly fewer days than either group used during the baseline period. MTM
      interventions were associated with a significant decrease in the MTM members'
      overall plan-paid health care costs, driven largely by decreases in inpatient
      utilization and mediated by increases in average days supply and in MPR increases
      for hypertension and dyslipidemia. Overall, the MTM program was cost-effective.
      The ROI estimated for this program of 2.0 is only slightly lower than the average
      disease management ROIs reported in the literature.

PMID- 23537458
TI  - Evaluating the short-term cost-effectiveness of liraglutide versus sitagliptin in
      patients with type 2 diabetes failing metformin monotherapy in the United States.
AB  - BACKGROUND: Effective glycemic control can reduce the risk of serious micro- and
      macrovascular complications in type 2 diabetes. However, many patients fail to
      reach glycemic targets due partly to low efficacy and adverse effects of
      treatment such as hypoglycemia or weight gain. OBJECTIVE: To evaluate the short
      term cost-effectiveness of liraglutide versus sitagliptin, in terms of cost per
      patient reaching a glycated hemoglobin (HbA1c) target with no hypoglycemia and no
      weight gain after 52 weeks, based on a recently published trial.  METHODS: Data
      were taken from a 52-week randomized, controlled trial (NCT00700817) in which
      adults with type 2 diabetes (mean age = 55 years, HbA1c = 8.4%, body mass index =
      33 kg/m2) failing metformin monotherapy were randomly allocated to receive either
      liraglutide 1.2 mg, liraglutide 1.8 mg, or sitagliptin 100 mg daily, in addition
      to metformin. For the cost-effectiveness analysis, the proportion of patients
      achieving a clinically relevant composite endpoint, defined as HbA1c  less than 
      7.0%, with no reported hypoglycemia ?and no gain in body weight, was estimated
      using logistic regression. Trial data showed that 38.9% of patients on
      liraglutide 1.2 mg and 49.9% on liraglutide 1.8 mg achieved the composite
      endpoint, compared with 18.6% on sitagliptin at 52 weeks. Costs of
      antihyperglycemia medications were accounted for based on published wholesale
      acquisition costs in 2012 U.S. dollars.  RESULTS: Overall pharmacy costs (needle
      costs included) were higher for patients on liraglutide than sitagliptin. The
      cost per patient achieving an HbA1c less than 7% was lowest for patients
      receiving liraglutide 1.2 mg ($7,993) and highest for patients receiving
      sitagliptin ($11,570). When expressed as the mean cost per patient reaching
      target HbA1c with no hypoglycemia or weight gain (cost of control), costs were
      notably lower on liraglutide than on sitagliptin. Annual mean costs of control
      were $10,335 on liraglutide 1.2 mg and $11,755 on liraglutide 1.8 mg versus
      $16,858 on sitagliptin. CONCLUSION: The mean cost per patient achieving control,
      defined as reaching HbA1c target with no hypoglycemia or weight gain, was lower
      with liraglutide than with sitagliptin based on data from a recently published 52
      week clinical trial. 

PMID- 23537459
TI  - Adherence to evidence-based therapies after acute coronary syndrome: a
      retrospective population-based cohort study linking hospital, outpatient, and
      pharmacy health information systems in Valencia, Spain.
AB  - BACKGROUND: Pharmacological secondary prevention in patients after an acute
      coronary syndrome (ACS) has contributed substantially to reductions in
      cardiovascular morbidity and mortality and, overall, has undergone important
      improvements in recent years. Nevertheless, there is still a considerable
      adherence gap and opportunity for improvement. OBJECTIVE: To assess, in a cohort
      of patients who survived an ACS, adherence to commonly prescribed secondary
      prevention drugs, factors associated to adherence, and variations among health
      care delivery areas. METHODS: We combined the medical and pharmacy databases from
      a regional public health service in Valencia, Spain, to construct a population
      based cohort of patients discharged alive after an emergency admission for an ACS
      to any hospital of the Valencia Health Agency in 2008. We evaluated medication
      adherence by determining the proportion of days covered (PDC) for each
      therapeutic group (antiplatelet agents, beta-blockers, angiotensin antagonists,
      and statins) in the 9 months following hospital discharge. Fully adherent
      patients were defined as those having enough treatment to cover 75% (PDC75) of
      the follow-up period. RESULTS: The study cohort consisted of 7,462 patients.
      PDC75 was reached by 69.9% of patients taking antiplatelet agents, 43.3% taking
      beta-blockers, 45.4% taking angiotensin antagonists, and 58.8% taking statins.
      Approximately 18% of patients did not reach PDC75 with any treatment, while 47.6%
      did so for 3 or more therapeutic groups. Lower adherence was found in diagnoses
      other than myocardial infarction. Other factors associated with nonadherence were
      older age, women, having copayment, foreign born, and most comorbidities (except
      for hypertension and hyperlipidemia, which were inversely associated, and
      diabetes and peripheral disease, which were not significantly associated). Health
      care delivery areas showed certain variability in their performance on these
      adherence measures that remained after the adjustment for covariates, although
      confidence intervals overlapped except between areas at the extremes.
      CONCLUSIONS: The proportion of fully adherent patients remains suboptimal, and
      important improvements are still possible in secondary prevention of ischemic
      heart disease. The combination of electronic health information systems may be
      very useful for monitoring adherence and evaluating the effectiveness of
      adherence and other quality improvement interventions.

PMID- 23537460
TI  - Impact of monthly prescription cap on medication persistence among patients with
      hypertension, hyperlipidemia, or diabetes.
AB  - BACKGROUND: Hypertension, hyperlipidemia, and diabetes are among the most
      prevalent and costly chronic health conditions affecting the U.S. population.
      Prescription treatments for these conditions are of critical importance to the
      health of patients, yet suboptimal adherence to prescription treatments for these
      conditions is not uncommon. While monthly prescription restriction has become a
      commonly used mechanism to reduce medication utilization, little is known about
      the effect of this policy on patients with hypertension, hyperlipidemia, or
      diabetes.   OBJECTIVES: To evaluate the effect of a reimbursement limit
      implemented in the Louisiana Medicaid program that restricted patients receiving
      8 prescriptions per month without prior authorization on continuation
      (persistence) of medications for hypertension, hyperlipidemia, or diabetes. 
      METHODS: A pre-post design was applied using Medicaid claims data from 2001-2003
      to compare medication persistence among patients in Louisiana (LA) to patients in
      Indiana (IN), a nonequivalent comparator state. Medication persistence was
      defined as time from treatment initiation to a treatment gap of 30 days or
      longer. To capture pre-intervention trends in medication persistence, we compared
      historical "pre-policy" cohorts in LA and IN followed for 10 months prior to
      policy adoption (March 3, 2002, to December 31, 2002) to "post-policy" cohorts
      followed for 10 months after policy adoption (March 3, 2003, to December 31,
      2003). All incident cohorts were identified using a 6-month washout period. We
      used Cox-proportional hazard models to compare discontinuation rates in LA and IN
      across the pre-policy and policy period cohorts.  RESULTS: The adjusted results
      showed no differences in persistence during the pre-policy period between LA and
      IN for any of the 3 chronic conditions. In the post-policy period, patients with
      hyperlipidemia in LA were 1.13 (95% CI = 1.02-1.25; P  less than  0.05) times
      more likely to discontinue their treatment as their IN counterparts, while no
      significant differences were observed in the hypertension or diabetes cohorts.  
      CONCLUSION: Our study suggests there is inconclusive evidence that the monthly
      prescription restriction disrupts the continuation of medications for common
      chronic health conditions in patients. More research is needed to identify which
      patients are most vulnerable to the effect of monthly prescription limits and how
      this policy could potentially affect additional treatment outcomes such as
      medication adherence, health outcomes, and Medicaid expenditures. 

PMID- 23537461
TI  - Using cited references to improve the retrieval of related biomedical documents.
AB  - BACKGROUND: A popular query from scientists reading a biomedical abstract is to
      search for topic-related documents in bibliographic databases. Such a query is
      challenging because the amount of information attached to a single abstract is
      little, whereas classification-based retrieval algorithms are optimally trained
      with large sets of relevant documents. As a solution to this problem, we propose
      a query expansion method that extends the information related to a manuscript
      using its cited references. RESULTS: Data on cited references and text sections
      in 249,108 full-text biomedical articles was extracted from the Open Access
      subset of the PubMed Central(r) database (PMC-OA). Of the five standard sections
      of a scientific article, the Introduction and Discussion sections contained most
      of the citations (mean = 10.2 and 9.9 citations, respectively). A large
      proportion of articles (98.4%) and their cited references (79.5%) were indexed in
      the PubMed(r) database. Using the MedlineRanker abstract classification tool,
      cited references allowed accurate retrieval of the citing document in a test set
      of 10,000 documents and also of documents related to six biomedical topics
      defined by particular MeSH(r) terms from the entire PMC-OA (p-value<0.01).
      Classification performance was sensitive to the topic and also to the text
      sections from which the references were selected. Classifiers trained on the
      baseline (i.e., only text from the query document and not from the references)
      were outperformed in almost all the cases. Best performance was often obtained
      when using all cited references, though using the references from Introduction
      and Discussion sections led to similarly good results. This query expansion
      method performed significantly better than pseudo relevance feedback in 4 out of
      6 topics. CONCLUSIONS: The retrieval of documents related to a single document
      can be significantly improved by using the references cited by this document (p
      value<0.01). Using references from Introduction and Discussion performs almost as
      well as using all references, which might be useful for methods that require
      reduced datasets due to computational limitations. Cited references from
      particular sections might not be appropriate for all topics. Our method could be
      a better alternative to pseudo relevance feedback though it is limited by full
      text availability.

PMID- 23537462
TI  - Electrical stimulation for chronic non-specific low back pain in a working-age
      population: a 12-week double blinded randomized controlled trial.
AB  - BACKGROUND: Non-invasive electrotherapy is commonly used for treatment of chronic
      low back pain. Evidence for efficacy of most electrotherapy modalities is weak or
      lacking. This study aims to execute a high-quality, double-blinded randomized
      controlled clinical trial comparing 1) H-Wave((r)) Device stimulation plus usual
      care with 2) transcutaneous electrical nerve stimulation (TENS) plus usual care,
      and 3) Sham electrotherapy plus usual care to determine comparative efficacy for
      treatment of chronic non-specific low back pain patients. METHODS/DESIGN: 
      PATIENTS: Chronic non-specific low back pain patients between ages of 18-65
      years, with pain of at least 3 months duration and minimal current 5/10 VAS pain.
      Patients will have no significant signs or symptoms of lumbosacral nerve
      impingement, malignancy, spinal stenosis, or mood disorders. STUDY DESIGN: Double
      blind RCT with 3 arms and 38 subjects per arm. Randomization by permuted blocks
      of random length, stratified by Workers Compensation claim (yes vs. no), and use
      of opioids. The null hypothesis of this study is that there are no statistically
      significant differences in functional improvement between treatment types during
      and at the end of a 12-week week treatment period. DATA COLLECTION: Subjective
      data will be collected using Filemaker ProTM database management collection
      tools. Objective data will be obtained through functional assessments. Data will
      be collected at enrollment and at 1, 4, 8, and 12 weeks for each participant by a
      blinded assessor. INTERVENTIONS: H-Wave((r)) device stimulation (Intervention A)
      plus usual care, transcutaneous electrical nerve stimulation (TENS) (Intervention
      B) plus usual care, and sham electrotherapy plus usual care (control). Each
      treatment arm will have identical numbers of visits (4) and researcher contact
      time (approximately 15 hours). OUTCOMES:  PRIMARY OUTCOME MEASURE: Oswestry
      Disability Index. Secondary measures include: Rowland Morris Instrument, VAS pain
      score, functional evaluation including strength when pushing and pulling, pain
      free range of motion in flexion and extension. Outcome measures assessed at
      baseline, 1, 4, 8, and 12 weeks. Treatment failure will be defined if patient
      terminates assigned treatment arm for non-efficacy or undergoes invasive
      procedure or other excluded cointerventions. Data will be analyzed using
      intention-to-treat analysis and adjusted for covariates related to LBP (e.g. age)
      as needed. DISCUSSION: Study strengths include complex randomization, treatment
      group allocation concealment, double blinding, controlling for co-interventions,
      rigorous inclusion criteria, assessment of compliance, plans for limiting
      dropout, identical assessment methods and timing for each treatment arm, and
      planned intention-to-treat analyses.

PMID- 23537463
TI  - Challenges for malaria elimination in Zanzibar: pyrethroid resistance in malaria
      vectors and poor performance of long-lasting insecticide nets.
AB  - BACKGROUND: Long-lasting insecticide treated nets (LLINs) and indoor residual
      house spraying (IRS) are the main interventions for the control of malaria
      vectors in Zanzibar. The aim of the present study was to assess the
      susceptibility status of malaria vectors against the insecticides used for LLINs
      and IRS and to determine the durability and efficacy of LLINs on the island.
      METHODS: Mosquitoes were sampled from Pemba and Unguja islands in 2010-2011 for
      use in WHO susceptibility tests. One hundred and fifty LLINs were collected from
      households on Unguja, their physical state was recorded and then tested for
      efficacy as well as total insecticide content. RESULTS: Species identification
      revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a
      small number of An. gambiae s.s. and An. merus being present. Susceptibility
      tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used
      for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible
      to all pyrethroids tested. A physical examination of 150 LLINs showed that two
      thirds were damaged after only three years in use. All used nets had a
      significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2
      compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly
      against both susceptible An. gambiae s.s. colony mosquitoes and wild-type
      mosquitoes from Pemba after just six washes (p < 0.001). CONCLUSION: The
      sustainability of the gains achieved in malaria control in Zanzibar is seriously
      threatened by the resistance of malaria vectors to pyrethroids and the short
      lived efficacy of LLINs. This study has revealed that even in relatively well
      resourced and logistically manageable places like Zanzibar, malaria elimination
      is going to be difficult to achieve with the current control measures.

PMID- 23537464
TI  - Lipoplexes versus nanoparticles: pDNA/siRNA delivery.
AB  - Small interfering RNA (siRNA) has been widely used as potential therapeutic for
      treatment of various genetic disorders. However, rapid degradation, poor cellular
      uptake and limited stability in blood limit the effectiveness of the systemic
      delivery of siRNA. Therefore, an efficient delivery system is required to enhance
      its transfection and duration of therapeutics. In the present study, plasmid DNA
      (pEGFPN3) expressing green fluorescent protein (GFP) was used as a reporter gene.
      Chitosan nanoparticles/polyplexes and cationic liposomes/lipoplexes were
      developed and compared for their transfectivity and therapeutic activity in
      mammalian cell line (HEK 293). The nanoparticulates were first characterized by
      assessing the surface charge (zeta potential), size (dynamic light scattering)
      and morphology (transmission electron microscope) followed by evaluation for
      their DNA retardation ability, transfection efficiency and cytotoxicity on HEK
      293 cell line. The chitosan nanoparticles/plasmid DNA (pDNA) complex and
      liposomes/pDNA complex were co-transfected with GFP-specific siRNA into HEK 293
      cells and it was found that both are efficient delivery vehicles for siRNA
      transfection, resulting in ~57% and ~70% suppression of the targeted gene (GFP),
      respectively, as compared with the mock control (cells transfected with
      nanocarrier/pDNA complexes alone). This strong inhibition of GFP expression
      indicated that cationic liposomes are better than chitosan nanoparticles and can
      be used as an effective carrier of siRNA in mammalian cells.

PMID- 23537465
TI  - Eudragit-coated aceclofenac-loaded pectin microspheres in chronopharmacological
      treatment of rheumatoid arthritis.
AB  - The aim of this study was to develop a pectin-based colon-specific
      multiparticulate delivery system. Aceclofenac was used as a model drug owing to
      its potential therapeutic efficacy in rheumatoid arthritis. Pectin microspheres
      were prepared using emulsion dehydration technique. These microspheres were
      coated with Eudragit S-100 using solvent evaporation method. The effect of
      different variables (polymer, emulsifier, stirring speed and stirring time) was
      investigated in terms of size, surface morphology, entrapment efficiency, in
      vitro release and in vivo studies. The size of uncoated microspheres ranged from
      30 to 55 um and exhibited 5-40% of drug release in the upper gastrointestinal
      tract; however, continuous high release of drug was observed at colonic pH. In
      addition, the release of drug from the microspheres was found to be higher in the
      presence of rat cecal contents with maximum release at the 8th hour. This is one
      of the prerequisites for the effective treatment of rheumatoid arthritis,
      indicating the effect of colonic enzymes on the pectin microspheres. In vivo
      studies suggest the maintenance of therapeutic concentration of drug for 24 h
      with significant anti-inflammatory effect. Therefore, these findings clearly
      suggest that the Eudragit-coated pectin microspheres offer an exciting mode of
      aceclofenac delivery to colon in the chronopharmacological treatment of
      rheumatoid arthritis.

PMID- 23537466
TI  - A fenestrated stent graft for surgical resection of lung cancer invading the
      aortic arch.

PMID- 23537467
TI  - Alternative access options for transcatheter aortic valve replacement in patients
      with no conventional access and chest pathology.
AB  - OBJECTIVE: Aortic stenosis is the most common valvular pathology in the elderly.
      Transcatheter aortic valve replacement has emerged as a safe and feasible
      alternative for high-risk patients. However, a significant number of patients are
      still not transcatheter aortic valve replacement candidates because of poor
      peripheral access and chest pathology. We report the use of alternative access
      options for such patients. METHODS: Seven patients who had poor peripheral access
      and chest pathology had transcatheter aortic valve replacement using alternative
      access techniques. Five patients had the valve delivered by direct cannulation of
      the aorta via a mini-sternotomy, and 1 patient had the valve delivered via a mini
      right thoracotomy. In 1 patient, the right subclavian artery was cannulated.
      Intraprocedural and 30-day outcome data were analyzed. RESULTS: The mean age of
      patients was 85.00 +/- 9.59 years, with a Society of Thoracic Surgeons score of
      16.81% +/- 6.87% and logistic European System for Cardiac Operative Risk
      Evaluation of 21.59% +/- 8.46%. Procedural success was 100%. Procedural and 30
      day mortality were zero. There were no access-related complications or neurologic
      events. Two patients had worsening renal function that did not require dialysis.
      All patients were discharged with a median hospital stay of 7 days. In our
      experience of 138 transapical or alternative access patients, 7 died (5%) and for
      257 transfemoral patients, 1 died (0.4%). CONCLUSIONS: Despite the high surgical
      risk of the study population, these techniques had excellent outcome with no
      mortality and acceptable morbidity. With the use of currently available
      technologies, these approaches are promising and offer alternative options in
      patients with no access and prohibitive chest pathology or pulmonary function.

PMID- 23537468
TI  - Efficiency, effectiveness, equity (E3). Evaluating hospital performance in three
      dimensions.
AB  - There are well-established frameworks for comparing the performance of health
      systems cross-nationally on multiple dimensions. A sub-set of such comprehensive
      schema is taken up by criteria specifically applied to health service delivery,
      including hospital performance. We focus on evaluating hospital performance,
      using the New Zealand public hospital sector over the period 2001-2009 as a
      pragmatic and illustrative case study for cross-national application. We apply a
      broad three-dimensional matrix--efficiency, effectiveness, equity--each based on
      two measures, and we undertake ranking comparisons of 35 hospitals. On the
      efficiency dimension--relative stay, day surgery--we find coefficients of
      variation of 10.8% and 8.5% respectively in the pooled data, and a slight trend
      towards a narrowing of inter-hospital variation over time. The correlation
      between these indicators is low (.20). For effectiveness--post-admission
      mortality, unplanned readmission--the coefficient of variation is generally
      higher (24.1% and 12.2%), and the trend is flat. The correlation is again low
      (.21). The equity dimension is assessed by quantifying the degree of ethnic and
      socio-economic variation for each hospital. The coefficient of variation is much
      higher--40.7-66.5% for ethnicity, 55.8-84.4% for socio-economic position--the
      trend over time is mixed, and the correlation is moderate (.41). On averaging the
      rank of hospitals across all measures it is evident that there is limited
      consistency across the three constituent dimensions. While it is possible to
      assess hospital performance across three dimensions using an illustrative set of
      standard measures derived from routine data, there appears to be little
      consistency in hospital rankings on these New Zealand data for the period 2001
      2009. However, the methodology of using rankings derived from readily available
      data--possibly allied with multiple or composite indicator models--has potential
      for the cross-national comparison of hospital profiles, and assessments in three
      dimensions provide a more holistic and rounded account of performance.

PMID- 23537470
TI  - A serious threat to patient safety: the unintended misuse of FentaNYL patches.

PMID- 23537471
TI  - Facilitating a safe transition from the pediatric emergency department to home
      with a post-discharge phone call: a quality-improvement initiative to improve
      patient safety.

PMID- 23537473
TI  - Systematic study of structural and thermodynamic properties of HCl(H2O)n clusters
      from semiempirical replica exchange simulations.
AB  - The structural and thermodynamic properties of HCl(H2O)n clusters with n = 4-10
      are studied using Born-Oppenheimer replica exchange molecular dynamics
      simulations with the PM3-MAIS semiempirical Hamiltonian. Independently of the
      cluster size, the simulations predict that HCl exists in the dissociated form in
      all low-energy isomers. Different local structures are identified within the
      clusters due to the presence of the dissociated proton, including Zundel, Eigen,
      Eigen-like, H7O3(+), and intermediate Zundel-Eigen configurations. As the cluster
      size increases, several groups of isomers are identified, whose relative
      stabilities vary as a function of temperature. A detailed analysis of the heat
      capacity indicates that the melting behavior of HCl(H2O)n clusters is strongly
      size-dependent. In particular, melting is observed in clusters with n = 7-10 in
      the temperature range T = 100-150 K. By contrast, melting is not observed in
      clusters with n = 4-6. Minimum energy structures for HCl(H2O)n clusters with n =
      11-15 and n = 21 are also characterized. 

PMID- 23537472
TI  - The effect of cyclodextrin-solubilized curcuminoids on amyloid plaques in
      Alzheimer transgenic mice: brain uptake and metabolism after intravenous and
      subcutaneous injection.
AB  - INTRODUCTION: Curcuminoids may improve pathological conditions associated with
      Alzheimer's disease. However, their therapeutic potential is limited by their
      exceedingly low bioavailability after oral administration. A method to deliver
      solubilized curcuminoids by injection was evaluated in Alzheimer transgenic mice.
      METHODS: Amyloid protein precursor (APP)SWE, PS1dE9 mice were intravenously or
      subcutaneously injected at weekly intervals between the ages of 4 and 12 months
      with serum- or cyclodextrin-solubilized curcuminoids to assess their potential
      for plaque prevention. Alternatively, mice between the ages of 11 and 12 months
      were intravenously injected with cyclodextrin-solubilized curcuminoids at
      biweekly intervals to evaluate their ability to eliminate existing plaques.
      Plasma and brain levels of curcuminoids and their metabolites were also
      determined after subcutaneous and intravenous injection. RESULTS: Weekly long
      term injections did not result in a significant plaque load reduction. However,
      intravenous injection of cyclodextrin-solubilized curcuminoids at higher
      curcuminoid concentrations and at a biweekly frequency between the ages of 11 and
      12 months reduced the plaque load to approximately 70% of the control value.
      After intravenous injection, plasma levels of 100 MUM curcuminoids and brain
      levels of 47 nmol/g could initially be achieved that declined to essentially
      undetectable levels within 20 minutes. The primary curcuminoid metabolites in
      plasma were the conjugates of glucuronide or sulfate and hexahydrocurcuminoids as
      reduction products. In the brain, both hexahydrocurcuminoids and
      octahydrocurcuminoids were detected as major metabolites. After subcutaneous
      injection, maximal curcuminoid plasma levels of 23 MUM and brain levels of 8
      nmol/g were observed at 30 minutes after injection and curcuminoids remained
      detectable for 2 to 3 h. CONCLUSION: Curcuminoids are rapidly metabolized after
      injection and their effect on reducing plaque load associated with Alzheimer's
      disease may be dependent on the frequency of administration.

PMID- 23537474
TI  - Can molecular cages be effective at small molecule activation? A computational
      investigation.
AB  - Several approaches have been investigated in recent years in the area of small
      molecule activation. The current work introduces a new concept in this field:
      that of molecular cages, containing only main group elements, serving to activate
      small molecules. Full quantum mechanical calculations employing DFT/SCS-MP2
      methods indicate that recently synthesized Ga-N cage compounds would be excellent
      candidates for mediating in important reactions such as the catalysis of ammonia
      borane dehydrogenation. The current work therefore opens up exciting new
      possibilities in small molecule activation research.

PMID- 23537475
TI  - The convergence between self-reports and observer ratings of financial skills and
      direct assessment of financial capabilities in patients with schizophrenia: more
      detail is not always better.
AB  - Despite multiple lines of evidence suggesting that people with schizophrenia tend
      to overestimate their ability to perform everyday tasks such as money management,
      self-report methods are still widely used to assess functioning. In today's
      technology driven financial world patients are faced with increasingly complex
      financial management tasks. To meet these challenges adequate financial skills
      are required. Thus, accurate assessments of these abilities are critical to
      decisions regarding a patient's need for support such as a financial trustee. As
      part of the larger VALERO study, 195 patients with schizophrenia were asked to
      self-report their everyday financial skills (five common financial tasks) with
      the Independent Living Skills Survey (ILSS). They were also assessed with
      performance-based measures of neuro-cognition and functional capacity with a
      focus on financial skills. In addition, a friend, relative, or clinician
      informant was interviewed with the ILSS and a best estimate rating of functioning
      was generated. Scores on the performance-based measures of financial skills and
      neuropsychological tests were uncorrelated with self-reported financial
      activities. Interviewer and all informant judgments of financial abilities were
      also minimally correlated with performance on functional skill tests. Discrete
      financial skills appear to be challenging for clinicians to rate with accuracy
      without the use of direct assessments. Direct assessment of financial skills
      seems prudent when making determinations about the need for guardianship or other
      financial supervision.

PMID- 23537476
TI  - Predicting compliance with command hallucinations: anger, impulsivity and
      appraisals of voices' power and intent.
AB  - Command hallucinations are experienced by 33-74% of people who experience voices,
      with varying levels of compliance reported. Compliance with command
      hallucinations can result in acts of aggression, violence, suicide and self-harm;
      the typical response however is non-compliance or appeasement. Two factors
      associated with such dangerous behaviours are anger and impulsivity, however few
      studies have examined their relationship with compliance to command
      hallucinations. The current study aimed to examine the roles of anger and
      impulsivity on compliance with command hallucinations in people diagnosed with a
      psychotic disorder. The study was a cross-sectional design and included
      individuals who reported auditory hallucinations in the past month. Subjects
      completed a variety of self-report questionnaire measures. Thirty-two people
      experiencing command hallucinations, from both in-patient and community settings,
      were included. The tendency to appraise the voice as powerful, to be impulsive,
      to experience anger and to regulate anger were significantly associated with
      compliance with command hallucinations to do harm. Two factors emerged as
      significant independent predictors of compliance with command hallucinations;
      omnipotence and impulsivity. An interaction between omnipotence and compliance
      with commands, via a link with impulsivity, is considered and important clinical
      factors in the assessment of risk when working with clients experiencing command
      hallucinations are recommended. The data is highly suggestive and warrants
      further investigation with a larger sample.

PMID- 23537478
TI  - One-pot synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives under mild
      conditions using iminium cation from cyanuric chloride/dimethylformamide as a
      cyclizing agent.
AB  - BACKGROUND: The derivatives of 2-substituted 4H-3,1-benzoxazin-4-one belong to a
      significant category of heterocyclic compounds, which have shown a wide spectrum
      of medical and industrial applications. RESULTS: A new and effective one-pot
      method for the synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives is
      described in this paper. By using the iminium cation from a mixture of cyanuric
      chloride and dimethylformamide as a cyclizing agent, a series of 2-substituted 4H
      3,1-benzoxazin-4-one derivatives was synthesized in high yield under mild
      conditions and simple workup. CONCLUSIONS: The iminium cation from a mixture of
      cyanuric chloride and N,N-dimethylformamide is an effective cyclizing agent for
      the room temperature one-pot synthesis of 2-substituted 4H-3,1-benzoxazin-4-one
      derivatives in high yields through a cyclodehydration reaction. Furthermore, the
      method was performed under mild conditions characterized by simplified pathways
      and workup, minimized energy, and fewer reaction steps, compared with the
      previous methods. The proposed method, which is a simpler alternative than the
      published methods, is applicable for the synthesis of other 2-substituted 4H-3,1
      benzoxazin-4-one derivatives.

PMID- 23537477
TI  - Comorbid substance abuse in first-episode schizophrenia: effects on cognition and
      psychopathology in the EUFEST study.
AB  - Studies and meta-analyses investigating the influence of substance use disorder
      (SUD) (substance abuse or dependence) on psychopathology and neurocognitive
      function in schizophrenia patients have revealed controversial results. Most
      studies did only have small samples and did not focus exclusively on first
      episode schizophrenia patients. METHOD: In a post-hoc analysis of the European
      First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive
      performances of patients with (FE-SUD, N=119, consisting of N=88 patients with
      persisting SUD at baseline and N=31 patients with previous SUD) and without SUD
      (FE-non-SUD, N=204) were compared at baseline and 6 months follow-up.
      Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT);
      Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding.
      RESULTS: In total 31.1% of patients reported SUD, and 22.2% of patients used
      cannabis. There were no significant differences between patients with and without
      SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive
      measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's
      d=0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients
      with ongoing substance use at follow-up showed elevated positive symptoms (PANSS
      positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS
      scores at baseline were increased in patients with an onset of SUD before the age
      of 16 years. In addition we found a correlation between longer duration of
      cannabis use and higher cognitive performance as well as reduced symptom
      improvement and more extrapyramidal motor symptoms in patients with higher
      frequency of cannabis consumption. CONCLUSIONS: FE-SUD and FE-non-SUD show
      similar psychopathology and neuropsychological performances at baseline and
      during the first 6 months of antipsychotic treatment.

PMID- 23537479
TI  - The effect of glycosaminoglycan enzymes and proteases on the viscosity of alpaca
      seminal plasma and sperm function.
AB  - In order to advance the development of cryopreservation and other assisted
      reproductive technologies in camelids it is necessary to eliminate the viscous
      component of the seminal plasma without impairing sperm function. It has been
      postulated that glycosaminoglycans (GAGs) or proteoglycans are responsible for
      this viscosity. This study investigated the effect of the GAG enzymes
      hyaluronidase, chondroitinase ABC and keratanase and the proteases papain and
      proteinase K on seminal plasma viscosity and sperm function in order to aid
      identification of the cause of seminal plasma viscosity and propose methods for
      the reduction of viscosity. Sperm motility, DNA integrity, acrosome integrity and
      viability were assessed during 2h incubation. All enzymes reduced seminal plasma
      viscosity compared to control (P<0.001) although papain was most effective,
      completely eliminating viscosity within 30 min of treatment. Sperm motility and
      DNA integrity was not affected by enzyme treatment. The proportion of viable,
      acrosome intact sperm was reduced in all enzyme treated samples except those
      treated with papain (P<0.001). These findings suggest that proteins, not GAGs are
      the main cause of alpaca seminal plasma viscosity. Papain treatment of alpaca
      semen may be a suitable technique for reduction of seminal plasma viscosity prior
      to sperm cryopreservation.

PMID- 23537480
TI  - Reproductive outcome with GnRH inclusion at 24 or 36h following a prostaglandin
      F2alpha-based protocol for timed AI in ewes.
AB  - The objective of this experiment was to study the reproductive performance
      obtained after a short-interval prostaglandin (PG) F2alpha-based protocol for
      timed artificial insemination (TAI) in sheep (Synchrovine(r): two injections of
      PG 7 d apart), including a GnRH analogue at 24 or 36h after the second PG
      injection. The experiment involved 296 Corriedale ewes (206 multiparous and 90
      nulliparous) grazing natural pastures during the breeding season (March-April;
      UTU "La Carolina", Flores Uruguay, 33 degrees  S-57 degrees  W). Ewes were
      assigned to three treatment groups: a) Synchrovine(r) (Control, n=101): two
      injections of D-Cloprostenol 75MUg, 7 d apart, b) Synchrovine(r)+GnRH24 (n=98):
      Synchrovine(r) plus GnRH (busereline acetate 8.4MUg) 24h after the second PG
      injection, and c) Synchrovine(r)+GnRH36 (n=97): Synchrovine(r) plus GnRH 36h
      after the second PG injection. All ewes were subjected to cervical TAI (Day 0),
      44 to 47h after second PG injection, with fresh extended semen pool from six
      rams. Reproductive performance of ewes having ovulations and ovulation rate on
      Day 10, estrous cycle length in ewes that returned to estrus and non-return rate
      to estrus up to Day 22, fertility, prolificacy and fecundity on Day 70 were
      analyzed. Ewes having ovulations, ovulation rate, estrous cycle length and
      prolificacy did not differ between groups (P>0.05). However, non-return to
      estrus, fertility and fecundity was decreased in Synchrovine(r)+GnRH24 (P<0.05)
      and similar between Synchrovine(r) and Synchrovine(r)+GnRH36 (P>0.05). It was
      concluded that the reproductive performance obtained by Synchovine(r) TAI
      protocol was impaired by GnRH at 24h and not improved by GnRH administered at 36h
      after the second PG injection.

PMID- 23537481
TI  - Perturbation in protein expression of the sterile salmonid hybrids between female
      brook trout Salvelinus fontinalis and male masu salmon Oncorhynchus masou during
      early spermatogenesis.
AB  - Most males and females of intergeneric hybrid (BM) between female brook trout
      (Bt) Salvelinus fontinalis and male masu salmon (Ms) Oncorhynchus masou had
      undeveloped gonads, with abnormal germ cell development shown by histological
      examination. To understand the cause of this hybrid sterility, expression
      profiles of testicular proteins in the BM and parental species were examined with
      2-DE coupled with MALDI-TOF/TOF MS. Compared with the parental species, more than
      60% of differentially expressed protein spots were down-regulated in BM. A total
      of 16 up-regulated and 48 down-regulated proteins were identified in BM. Up
      regulated were transferrin and other somatic cell-predominant proteins, whereas
      down-regulated were some germ cell-specific proteins such as DEAD box RNA
      helicase Vasa. Other pronouncedly down-regulated proteins included tubulins and
      heat shock proteins that are supposed to have roles in spermatogenesis. The
      present findings suggest direct association of the observed perturbation in
      protein expression with the failure of spermatogenesis and the sterility in the
      examined salmonid hybrids.

PMID- 23537482
TI  - The effectiveness of recombinant OL fusion protein (ovalbumin-LHRH-7) in
      suppressing reproductive functions when injected in single-dose vaccination
      protocols with different adjuvants.
AB  - The objective of this study was to evaluate the effectiveness of recombinant LHRH
      fusion protein, Ovalbumin-LHRH-7 (OL), using a single-dose vaccination protocol
      in combination with different adjuvants in suppressing reproductive functions in
      buck kids. For this purpose, either a mixture of free OL antigen and encapsulated
      OL antigen, or encapsulated OL antigen was used. Thirty-nine native buck kids at
      12 weeks of age were divided into control (n=7) and treatment groups (n=8
      bucks/group). The four treatment groups were formed according to the different
      vaccine formulations: Group CpG received 0.5mg free OL protein together with
      1.0mg of encapsulated protein with CpG adjuvant. Group mFCA received 0.5mg free
      OL protein together with 1.0mg of encapsulated protein with modified Freund's
      complete adjuvant. Group IS received 1.5mg encapsulated OL protein with a mix of
      inulin and saponin adjuvants. Group ISmFCA received 1.5mg encapsulated OL protein
      with a mix of inulin, saponin and modified Freund's complete adjuvants. Scrotal
      circumference in CpG and mFCA groups were significantly smaller than that of
      Control, IS and ISmFCA groups (P<0.05). Numbers and percentage of bucks having
      spermatozoa in their ejaculate were significantly lower in CpG and mFCA groups
      (P<0.05). OL immunization completely suppressed sperm production, except one
      buck, in CpG and mFCA groups (P<0.05). These results imply that it is possible to
      use OL protein in a single injection protocol for the purpose of
      immunocastration. Further investigation with a larger number of animals should be
      carried out to determine the longevity of response to a single injection.

PMID- 23537483
TI  - Network analysis: an integrative approach to the structure of psychopathology.
AB  - In network approaches to psychopathology, disorders result from the causal
      interplay between symptoms (e.g., worry -> insomnia -> fatigue), possibly
      involving feedback loops (e.g., a person may engage in substance abuse to forget
      the problems that arose due to substance abuse). The present review examines
      methodologies suited to identify such symptom networks and discusses network
      analysis techniques that may be used to extract clinically and scientifically
      useful information from such networks (e.g., which symptom is most central in a
      person's network). The authors also show how network analysis techniques may be
      used to construct simulation models that mimic symptom dynamics. Network
      approaches naturally explain the limited success of traditional research
      strategies, which are typically based on the idea that symptoms are
      manifestations of some common underlying factor, while offering promising
      methodological alternatives. In addition, these techniques may offer
      possibilities to guide and evaluate therapeutic interventions.

PMID- 23537484
TI  - Fear extinction and relapse: state of the art.
AB  - Exposure-based treatments for clinical anxiety generally are very effective, but
      relapse is not uncommon. Likewise, laboratory studies have shown that conditioned
      fears are easy to extinguish, but they recover easily. This analogy is striking,
      and numerous fear extinction studies have been published that highlight the
      processes responsible for the extinction and return of acquired fears. This
      review examines and integrates the most important results from animal and human
      work. Overall, the results suggest that fear extinction is relatively easy to
      "learn" but difficult to "remember." It follows that treatments will benefit from
      an enhanced focus on the long-term retrieval of fear extinction. We review the
      available studies on the prevention of return of fear and the prospects of
      weakening fear memories forever. We show that the behavioral principles outlined
      in learning theory provide a continuous inspiration for preclinical
      (neurobiological) and clinical research on the extinction and return of fear.

PMID- 23537485
TI  - Social anxiety and social anxiety disorder.
AB  - Research on social anxiety and social anxiety disorder has proliferated over the
      years since the explication of the disorder through cognitive-behavioral models.
      This review highlights a recently updated model from our group and details recent
      research stemming from the (a) information processing perspective, including
      attention bias, interpretation bias, implicit associations, imagery and visual
      memories, and (b) emotion regulation perspective, including positive emotionality
      and anger. In addition, we review recent studies exploring the roles of self
      focused attention, safety behaviors, and post-event processing in the maintenance
      of social anxiety. Within each area, we detail the ways in which these topics
      have implications for the treatment of social anxiety and for future research.
      Finally, we conclude with a discussion of how several of the areas reviewed
      contribute to our model of social anxiety disorder.

PMID- 23537487
TI  - Depression and cardiovascular disorders.
AB  - During the past two decades, research in the field of depression and
      cardiovascular disorders has exploded. Multiple studies have demonstrated that
      depression is more prevalent in populations with cardiovascular disease, is a
      robust risk factor for the development of cardiovascular disease in healthy
      populations, and is predictive of adverse outcomes (such as myocardial infarction
      and death) among populations with preexisting cardiovascular disease. Mechanistic
      studies have shown that poor health behaviors, such as physical inactivity,
      medication nonadherence, and smoking, strongly contribute to this association.
      Small randomized trials have found that antidepressant therapies may improve
      cardiac outcomes. Based on this accumulating evidence, the American Heart
      Association has recommended routine screening for depression in all patients with
      coronary heart disease. This review examines the key epidemiological literature
      on depression and cardiovascular disorders and discusses our current
      understanding of the mechanisms responsible for this association. We also examine
      current recommendations for screening, diagnosis, and management of depression.
      We conclude by highlighting new research areas and discussing therapeutic
      management of depression in patients with cardiovascular disorders.

PMID- 23537486
TI  - Worry and generalized anxiety disorder: a review and theoretical synthesis of
      evidence on nature, etiology, mechanisms, and treatment.
AB  - Generalized anxiety disorder (GAD) is associated with substantial personal and
      societal cost yet is the least successfully treated of the anxiety disorders. In
      this review, research on clinical features, boundary issues, and naturalistic
      course, as well as risk factors and maintaining mechanisms (cognitive,
      biological, neural, interpersonal, and developmental), are presented. A synthesis
      of these data points to a central role of emotional hyperreactivity, sensitivity
      to contrasting emotions, and dysfunctional attempts to cope with strong emotional
      shifts via worry. Consistent with the Contrast Avoidance model, evidence shows
      that worry evokes and sustains negative affect, thereby precluding sharp
      increases in negative emotion. We also review current treatment paradigms and
      suggest how the Contrast Avoidance model may help to target key fears and
      avoidance tendencies that serve to maintain pathology in GAD.

PMID- 23537488
TI  - Revisiting the relationship between autism and schizophrenia: toward an
      integrated neurobiology.
AB  - Schizophrenia and autism have been linked since their earliest descriptions. Both
      are disorders of cerebral specialization originating in the embryonic period.
      Genetic, molecular, and cytologic research highlights a variety of shared
      contributory mechanisms that may lead to patterns of abnormal connectivity
      arising from altered development and topology. Overt behavioral pathology likely
      emerges during or after neurosensitive periods in which resource demands
      overwhelm system resources and the individual's ability to compensate using
      interregional activation fails. We are at the threshold of being able to chart
      autism and schizophrenia from the inside out. In so doing, the door is opened to
      the consideration of new therapeutics that are developed based upon molecular,
      synaptic, and systems targets common to both disorders.

PMID- 23537489
TI  - The genetics of eating disorders.
AB  - Over the past decade, considerable advances have been made in understanding
      genetic influences on eating pathology. Eating disorders aggregate in families,
      and twin studies reveal that additive genetic factors account for approximately
      40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge
      eating disorder (BED). Molecular genetics studies have been undertaken to
      identify alterations in deoxyribonucleic acid sequence and/or gene expression
      that may be involved in the pathogenesis of disordered eating behaviors,
      symptoms, and related disorders and to uncover potential genetic variants that
      may contribute to variability of treatment response. This article provides an in
      depth review of the scientific literature on the genetics of AN, BN, and BED
      including extant studies, emerging hypotheses, future directions, and clinical
      implications.

PMID- 23537490
TI  - Rebirth and renewal through research--new evidence and strategies for improving
      the quality of pediatric nursing care.

PMID- 23537491
TI  - Divorce and children with chronic disorders: diabetes as an exemplar.

PMID- 23537492
TI  - Effectiveness of a motivational interviewing intervention on weight loss,
      physical activity and cardiovascular disease risk factors: a randomised
      controlled trial with a 12-month post-intervention follow-up.
AB  - BACKGROUND: Intensive diet and physical activity interventions have been found to
      reduce cardiovascular disease (CVD) risk, but are resource intensive. The
      American Heart Association recently recommended motivational interviewing (MI) as
      an effective approach for low-intensity interventions to promote health-related
      outcomes such as weight loss. However, there is limited research evaluating the
      long-term effectiveness of MI-based interventions on health-related outcomes
      associated with CVD risk. The current research evaluated the effectiveness of a
      six-month low-intensity MI intervention in a UK primary-care setting in
      maintaining reductions in CVD risk factors at12 months post-intervention.
      METHODS: Primary-care patients were randomised to an intervention group that
      received standard exercise and nutrition information plus up to five face-to-face
      MI sessions, delivered by a physical activity specialist and registered dietician
      over a 6-month period, or to a minimal intervention comparison group that
      received the standard information only. Follow-up measures of behavioural
      (vigorous and moderate physical activity, walking, physical activity stage-of
      change, fruit and vegetable intake, and dietary fat intake) and biomedical
      (weight, body mass index [BMI], blood pressure, cholesterol) outcomes were taken
      immediately post-intervention and at a 12-month follow-up occasion. RESULTS:
      Intent-to-treat analyses revealed significant differences between groups for
      walking and cholesterol. Obese and hypercholesterolemic patients at baseline
      exhibited significant improvements in BMI and cholesterol respectively among
      those allocated to the intervention group compared to the comparison group. Post
      intervention improvements in other health-related outcomes including blood
      pressure, weight, and BMI were not maintained. CONCLUSIONS: The present study
      suggests that a low-intensity MI counselling intervention is effective in
      bringing about long-term changes in some, but not all, health-related outcomes
      (walking, cholesterol levels) associated with CVD risk. The intervention was
      particularly effective for patients with elevated levels of CVD risk factors at
      baseline. Based on these findings future interventions should be conducted in a
      primary care setting and target patients with high risk of CVD. Future research
      should investigate how the long-term gains in health-related outcomes brought
      about by the MI-counselling intervention in the current study could be extended
      to a wider range of health outcomes.

PMID- 23537493
TI  - Physical health in a Canadian Old Order Mennonite community.
AB  - INTRODUCTION: This article explores physical health and its determinants in two
      rural populations in Waterloo, Canada: Old Order Mennonites (OOMs) and non-OOM
      farmers. OOMs were selected because their distinct lifestyle might offer health
      benefits, and cultural homogeneity and isolation might more clearly expose the
      determinants shaping their health. Comparing the two Waterloo groups reduces the
      effect of contextual features impacting both, such as local economic conditions.
      The study considers a comprehensive list of determinants in order to evaluate
      their relative importance in shaping physical health. This information enables
      policy action to focus on the determinants having the greatest impact. METHODS: A
      survey was used to obtain information from both groups on health status and
      health determinants. The survey was distributed in spring-summer 2010. All
      members of both groups were invited to complete the survey anonymously. The
      physical component summary (PCS) score of the SF-12 survey was used to measure
      physical health status. Age-gender breakdowns of PCS scores for both groups were
      compared, and differences evaluated using statistical significance and the
      interpretation cut-off recommended by SF-12 developers. Multiple (ordinary least
      squares) regression was used to identify key determinants shaping health. In the
      regressions, PCS scores represented the (continuous) dependent variable and the
      determinants of health were the independent variables. RESULTS: Non-OOMs were
      found to experience better physical health than OOMs, with mean PCS scores of
      49.24 for non-OOMs versus 47.39 for OOMs. The difference in PCS scores (1.85) was
      statistically significant (p=.002) and above the interpretation cut-off. While
      PCS score differences were significant for both genders, differences among the
      women were larger. OOM men and women may face health risks due to low incomes,
      offspring out-migrations and health service usage. OOM women may face additional
      risks related to reproductive health and gender role. Physical health in both
      groups is significantly shaped by coping, body mass index, childhood disease
      history and age. These determinants were more influential than factors such as
      social capital, sense-of-place and spirituality, which is particularly unexpected
      in OOMs given the strength of the social factors. CONCLUSIONS: The determinants
      shaping physical health in both groups (coping, body mass index, childhood
      disease history, age) are consistent with other studies on urban populations and
      people whose life circumstances vary widely. Therefore, these determinants
      represent targets for policy action because of their potential for widespread
      population health impacts. Ultimately, the fundamental health risk factors faced
      by small, isolated populations like OOMs appear to be common to other rural and
      general populations. The absence of social factors in shaping physical health in
      both groups differs from a number of social capital studies, and suggests there
      may be unique characteristics of rural or farming populations (eg high levels of
      self-reliance and independence). However, this could also reflect fundamental
      differences between physical and mental health, since other analyses show that
      social factors influence mental health. Understanding the absence of social
      factors in shaping physical health would benefit from better reconciliation of
      this study with others, but this is hampered by differences in health outcomes,
      models and measures employed across studies.

PMID- 23537494
TI  - Which criteria should be used to define type 2 diabetes remission after bariatric
      surgery?
AB  - BACKGROUND: Comparison of diabetes remission rates after bariatric surgery using
      two different models of criteria. METHODS: Retrospective analysis of data from
      110 patients with type 2 diabetes and morbid obesity who underwent bariatric
      surgery, preoperatively and at 18-month follow-up. Comparison of two models of
      remission: 1) 2009 consensus statement criteria; 2) simple criteria using ADA's
      HbA1c diabetes diagnostic cut-off values. RESULTS: Patients' mean +/- SD
      preoperative characteristics were: age 53.3 +/- 9.5 years, BMI 43.6 +/- 5.5
      kg/m(2), HbA1c 7.9 +/- 1.8%, duration of diabetes 7.6 +/- 7.5 years. 44.5% of
      patients with previous insulin therapy. With 2009 consensus statement criteria:
      complete, partial and no remission in 50%, 12.7% and 37.3%, respectively; with
      HbA1c criteria: 50%, 15% and 34.5% in the analogous categories (p=0.673).
      CONCLUSIONS: We suggest a simpler approach to evaluate diabetes remission after
      bariatric surgery, following the rationale of the definition of diabetes itself.

PMID- 23537496
TI  - 3D imaging of flow patterns in an internally-pumped microfluidic device: redox
      magnetohydrodynamics and electrochemically-generated density gradients.
AB  - Redox magnetohydrodynamics (MHD) is a promising technique for developing new
      electrochemical-based microfluidic flow devices with unique capabilities, such as
      easily switching flow direction and adjusting flow speeds and flow patterns as
      well as avoiding bubble formation. However, a detailed description of all the
      forces involved and predicting flow patterns in confined geometries is lacking.
      In addition to redox-MHD, density gradients caused by the redox reactions also
      play important roles. Flow in these devices with small fluid volumes has mainly
      been characterized by following microbead motion by optical microscopy either by
      particle tracking velocimetry (PTV) or by processing the microbead images by
      particle image velocimetry (PIV) software. This approach has limitations in
      spatial resolution and dimensionality. Here we use fluorescence correlation
      spectroscopy (FCS) to quantitatively and accurately measure flow speeds and
      patterns in the ~5-50 MUm/s range in redox-MHD-based microfluidic devices, from
      which 3D flow maps are obtained with a spatial resolution down to 2 MUm. The 2
      MUm spatial resolution flow speeds map revealed detailed flow profiles during
      redox-MHD in which the velocity increases linearly from above the electrode and
      reaches a plateau across the center of the cell. By combining FCS and video
      microscopy (with PTV and PIV processing approaches), we are able to quantify a
      vertical flow of ~10 MUm/s above the electrodes as a result of density gradients
      caused by the redox reactions and follow convection flow patterns. Overall,
      combining FCS, PIV, and PTV analysis of redox-MHD is a powerful combination to
      more thoroughly characterize the underlying forces in these promising
      microfluidic devices.

PMID- 23537497
TI  - Hot temperatures can force delayed mosquito outbreaks via sequential changes in
      Aedes aegypti demographic parameters in autocorrelated environments.
AB  - Aedes aegypti L. (Diptera: Culicidae) is a common pantropical urban mosquito,
      vector of dengue, Yellow Fever and chikungunya viruses. Studies have shown Ae.
      aegypti abundance to be associated with environmental fluctuations, revealing
      patterns such as the occurrence of delayed mosquito outbreaks, i.e., sudden
      extraordinary increases in mosquito abundance following transient extreme high
      temperatures. Here, we use a two-stage (larvae and adults) matrix model to
      propose a mechanism for environmental signal canalization into demographic
      parameters of Ae. aegypti that could explain delayed high temperature induced
      mosquito outbreaks. We performed model simulations using parameters estimated
      from a weekly time series from Thailand, assuming either independent or
      autocorrelated environments. For autocorrelated environments, we found that long
      delays in the association between the onset of "hot" environments and mosquito
      outbreaks (10 weeks, as observed in Thailand) can be generated when "hot"
      environments sequentially trigger a larval survival decrease and over
      compensatory fecundity increase, which lasts for the whole "hot" period, in
      conjunction with a larval survival increase followed by a fecundity decrease when
      the environment returns to "normal". This result was not observed for independent
      environments. Finally, we discuss our results implications for prospective
      entomological research and vector management under changing environments. 

PMID- 23537498
TI  - Computing minimal nutrient sets from metabolic networks via linear constraint
      solving.
AB  - BACKGROUND: As more complete genome sequences become available, bioinformatics
      challenges arise in how to exploit genome sequences to make phenotypic
      predictions. One type of phenotypic prediction is to determine sets of compounds
      that will support the growth of a bacterium from the metabolic network inferred
      from the genome sequence of that organism. RESULTS: We present a method for
      computationally determining alternative growth media for an organism based on its
      metabolic network and transporter complement. Our method predicted 787
      alternative anaerobic minimal nutrient sets for Escherichia coli K-12 MG1655 from
      the EcoCyc database. The program automatically partitioned the nutrients within
      these sets into 21 equivalence classes, most of which correspond to compounds
      serving as sources of carbon, nitrogen, phosphorous, and sulfur, or combinations
      of these essential elements. The nutrient sets were predicted with 72.5% accuracy
      as evaluated by comparison with 91 growth experiments. Novel aspects of our
      approach include (a) exhaustive consideration of all combinations of nutrients
      rather than assuming that all element sources can substitute for one another(an
      assumption that can be invalid in general) (b) leveraging the notion of a
      machinery-duplicating constraint, namely, that all intermediate metabolites used
      in active reactions must be produced in increasing concentrations to prevent
      successive dilution from cell division, (c) the use of Satisfiability Modulo
      Theory solvers rather than Linear Programming solvers, because our approach
      cannot be formulated as linear programming, (d) the use of Binary Decision
      Diagrams to produce an efficient implementation. CONCLUSIONS: Our method for
      generating minimal nutrient sets from the metabolic network and transporters of
      an organism combines linear constraint solving with binary decision diagrams to
      efficiently produce solution sets to provided growth problems.

PMID- 23537499
TI  - Real-time evaluation of milk quality as reflected by clotting parameters of
      individual cow's milk during the milking session, between day-to-day and during
      lactation.
AB  - Real-time analysis of milk coagulation properties as performed by the AfiLabTM
      milk spectrometer introduces new opportunities for the dairy industry. The study
      evaluated the performance of the AfiLabTM in a milking parlor of a commercial
      farm to provide real-time analysis of milk-clotting parameters -Afi-CF for cheese
      manufacture and determine its repeatability in time for individual cows. The
      AfiLabTM in a parlor, equipped with two parallel milk lines, enables to divert
      the milk on-line into two bulk milk tanks (A and B). Three commercial dairy herds
      of 220 to 320 Israeli Holstein cows producing ~11 500 l during 305 days were
      selected for the study. The Afi-CF repeatability during time was found
      significant (P < 0.001) for cows. The statistic model succeeded in explaining
      83.5% of the variance between Afi-CF and cows, and no significant variance was
      found between the mean weekly repeated recordings. Days in milk and log somatic
      cell count (SCC) had no significant effect. Fat, protein and lactose
      significantly affected Afi-CF and the empirical van Slyke equation. Real-time
      simulations were performed for different cutoff levels of coagulation properties
      where the milk of high Afi-CF cutoff value was channeled to tank A and the lower
      into tank B. The simulations showed that milk coagulation properties of an
      individual cow are not uniform, as most cows contributed milk to both tanks.
      Proportions of the individual cow's milk in each tank depended on the selected
      Afi-CF cutoff. The assessment of the major causative factors of a cow producing
      low-quality milk for cheese production was evaluated for the group that produced
      the low 10% quality milk. The largest number of cows in those groups at the three
      farms was found to be cows with post-intramammary infection with Escherichia coli
      and subclinical infections with streptococci or coagulase-negative staphylococci
      (~30%), although the SCC of these cows was not significantly different. Early
      time in lactation together with high milk yield >50 l/day, and late in lactation
      together with low milk yield<15 l/day and estrous (0 to 5 days) were also
      important influencing factors for low-quality milk. However, ~50% of the tested
      variables did not explain any of the factors responsible for the cow producing
      milk in the low - 10% Afi-CF.

PMID- 23537500
TI  - NMDA receptor-dependent function and plasticity in inhibitory circuits.
AB  - NMDA receptors have been known to play a central role in long-term potentiation
      at glutamatergic synapses in principal cells for thirty years. In contrast, their
      roles in the development and activity-dependent plasticity of synapses in
      inhibitory circuits have only recently begun to be understood. Progress has, to a
      great extent, been hampered by the extensive diversity of GABAergic cell types in
      the CNS. However, anatomical, immunohistochemical and electrophysiological
      methods have allowed distinct types to be identified, with the result that
      consistent patterns of synaptic plasticity have begun to emerge. This review
      summarizes recent evidence on the role of NMDA receptors in the development and
      plasticity of GABAergic synapses on principal cells and of glutamatergic synapses
      on identified interneurons. A major challenge is to understand how NMDA receptors
      affect the routing of information in healthy inhibitory circuits, and how changes
      in NMDA receptor function may contribute to altered circuit function in disorders
      such as schizophrenia. This article is part of the Special Issue entitled
      'Glutamate Receptor-Dependent Synaptic Plasticity'. 

PMID- 23537501
TI  - High-resolution rovibrational spectroscopy of jet-cooled phenyl radical: the nu19
      out-of-phase symmetric CH stretch.
AB  - Phenyl radical has been studied via sub-Doppler infrared spectroscopy in a slit
      supersonic discharge expansion source, with assignments for the highest frequency
      b2 out-of-phase C-H symmetric stretch vibration (nu19) unambiguously confirmed by
      <=6 MHz (0.0002 cm(-1)) agreement with microwave ground state combination
      differences of McMahon et al. [Astrophys. J. 2003, 590, L61-64]. Least squares
      analysis of over 100 resolved rovibrational peaks in the sub-Doppler spectrum to
      a Watson Hamiltonian yields precision excited-state rotational constants and a
      vibrational band origin (nu0 = 3071.8915(4) cm(-1)) consistent with a
      surprisingly small red-shift (0.9 cm(-1)) with respect to Ar matrix isolation
      studies of Ellison and co-workers [J. Am. Chem. Soc. 2001, 123, 1977]. Nuclear
      spin weights and inertial defects confirm the vibrationally averaged planarity
      and (2)A1 rovibronic symmetry of phenyl radical, with analysis of the rotational
      constants consistent with a modest C2v distortion of the carbon backbone frame
      due to partial sp rehybridization of the sigma C radical-center. Most
      importantly, despite the number of atoms (N = 11) and vibrational modes (3N - 6 =
      27), phenyl radical exhibits a remarkably clean jet cooled high-resolution IR
      spectrum that shows no evidence of intramolecular vibrational relaxation (IVR)
      phenomena such as local or nonlocal perturbations due to strongly coupled nearby
      dark states. This provides strong support for the feasibility of high-resolution
      infrared spectroscopy in other aromatic hydrocarbon radical systems. 

PMID- 23537502
TI  - Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance,
      response and remission in mood disorder patients.
AB  - Treatment resistant depression (TRD) is a significant clinical and public health
      problem. Among others, neuroplasticity and inflammatory pathways seem to play a
      crucial role in the pathomechanisms of antidepressant efficacy. The primary aim
      of this study was to investigate whether a set of single nucleotide polymorphisms
      (SNPs) within two genes implicated in neuroplasticity and inflammatory processes
      (the mitogen activated protein kinase 1, MAPK1 (rs3810608, rs6928, rs13515 and
      rs8136867), and the cyclic AMP responsive element binding protein 1, CREB1
      (rs889895, rs6740584, rs2551922 and rs2254137)) was associated with
      antidepressant treatment resistance (according to two different definitions), in
      285 Major Depressive Disorder (MDD) patients. As secondary aims, we investigated
      the genetic modulation of the same SNPs on response, remission and other clinical
      features both in MDD patients and in a larger sample including 82 Bipolar
      Disorder (BD) patients as well. All patients were screened in the context of a
      European multicenter project. No association between both the investigated genes
      and treatment resistance and response was found in MDD patients. However,
      considering remission, higher rates of CREB1 rs889895 GG genotype were reported
      in MDD patients. Moreover, MAPK1 rs8136867 AG genotype was found to be associated
      with remission in the whole sample (MDD and BD). Present results suggest that
      some genetic polymorphisms in both CREB1 and MAPK1 could be associated with
      treatment remission. Although further research is needed to draw more definitive
      conclusions, such results are intriguing since suggest a potential role of two
      genes implicated in neuroplasticity and inflammatory processes in symptom
      remission after antidepressant treatment.

PMID- 23537503
TI  - Nanocarrier systems for oral drug delivery: do we really need them?
AB  - In particular since the last two decades there is constantly increasing interest
      in nanocarrier systems. They are utilized in order to overcome the major
      challenges being associated with this route of administration - namely poor
      solubility (I), poor permeability (II) and poor GI-stability (III). In order to
      improve drug solubility nanonization of the API, the use of solid lipid
      nanoparticles and porous adsorbent particles have shown great potential.
      Nanocrystals and selfnanoemulsifying drug delivery systems (SNEDDS) resulted
      already in numerous marketed drug products. Moreover, proof-of-principle studies
      for nanocarrier systems providing enhanced oral drug uptake are available. By
      providing a comparatively more intimate contact with the absorption membrane, a
      prolonged GI-residence time and/or exhibiting permeation enhancing properties,
      oral absorption can be strongly improved. Likely because of safety considerations
      and because of insufficiently high bioavailability improvements (<5-fold),
      however, a commercial interest in these systems is limited. Poor GI-stability can
      be overcome by incorporating the drug in nanocarrier systems providing a
      protective effect towards an enzymatic attack in the GI-tract. Furthermore, as
      nanocarrier systems can at least to some extent diffuse into the mucus gel layer
      releasing their payload there, a presystemic metabolism of the drug on the way
      between the delivery system and the absorption membrane can be excluded. Future
      trends are mainly focusing on carrier systems capable of not just improving
      solubility but providing also controlled drug release as well as on nanocarrier
      systems capable of efficiently permeating the mucus gel layer without destroying
      it.

PMID- 23537504
TI  - Chronic obstructive pulmonary disease and vascular disease delay timeliness of
      early stage lung cancer resectional surgery.
AB  - INTRODUCTION: Lung cancer remains the leading cause of cancer death in the United
      States and worldwide. Timeliness to diagnosis and referral for resectional
      surgery is key to successful management for early stage disease. METHODS: We
      investigated the contribution of medical co-morbidities in the timeliness to
      resectional surgery for non-small cell lung cancer (NSCLC). A retrospective
      record review of NSCLC surgery cases at Naval Medical Center San Diego (NMCSD)
      from 2004 to 2009 from the tumor registry was conducted. RESULTS: More than 75%
      of NSCLC patients exhibited at least one co-morbidity. Of the 84 patients, 26% of
      patients had diabetes, patients with different vascular co-morbidities accounted
      for 39%, whereas 33% of subjects had COPD. Patients with sleep apnea or liver
      disease each accounted for 6%. Vascular disease co-morbidity and COPD in NSCLC
      patients significantly delayed time from initial cardiothoracic surgery
      evaluation to thoracotomy (p = 0.01-0.02 and p < 0.05 respectively). CONCLUSION:
      Although significances of different co-morbities in the development NSCLC cannot
      be extrapolated, theses data show that COPD and vascular diseases are significant
      risk factors that delay surgical treatment of early stage lung cancer.

PMID- 23537505
TI  - Novel future therapeutic options in myasthenia gravis.
AB  - BACKGROUND: Myasthenia Gravis (MG) is an autoimmune disease caused by complement
      fixing antibodies against the acetylcholine receptors (AChR). Antigen-specific
      CD4+ T cells, Tregs and Th17+ are also necessary. Consequently, antibodies, B
      cells, molecules associated with signalling pathways on T helper cells, cytokines
      and complement are targets for more specific treatment options. OBJECTIVES:
      Because available immunosuppressive therapies cause unacceptable side effects
      after long-term use or are not always effective in inducing remission, novel
      biological agents directed against the following targets might be options for
      future therapies in MG: 1) T cell Intracellular Signaling Pathways associated
      with T cell activation, such as monoclonal antibodies against CD52, Interleukin 2
      receptor (IL-2 R), co-stimulatory molecules or compounds inhibiting Janus
      tyrosine kinases JAK1, JAK3; 2) B cells, against key B cell-surface molecules or
      trophic factors B cell activation factor (BAFF) and a proliferating inducing
      ligand (APRIL); 3) Complement, against C3 or C5 that intercept membranolytic
      attack complex formation; 4) Cytokines and cytokine receptors, including IL-6, IL
      17, the p40 subunit of IL12/1L-23, and GM-CSF; and 5) Lymphocyte migration
      molecules. Construction of recombinant AChR antibodies that block the binding of
      the pathogenic antibodies, can be a future molecular tool. CONCLUSION: New
      biological agents are in the offing for future therapies in MG. Their efficacy
      needs to be secured with vigorously controlled clinical trials and weighted
      against excessive cost and rare complications.

PMID- 23537506
TI  - Mechanisms associated with the pathogenicity of antibodies against muscle
      specific kinase in myasthenia gravis.
AB  - The presence of autoantibodies against muscle-specific kinase (MuSK) at the
      neuromuscular junction (NMJ) results in myasthenia gravis (MG). MuSK antibody
      associated MG (MuSK MG) patients often have severe symptoms, including bulbar
      dysfunction, respiratory insufficiency and atrophy of the facial and tongue
      muscles. MuSK antibodies in MG patients predominantly belong to the IgG4
      subclass, and the unique properties of IgG4 antibodies are directly associated
      with the pathogenic mechanisms of MuSK MG. Histopathological studies in animal
      models of MuSK MG have revealed that anti-MuSK antibodies cause contraction of
      motor terminals, significant loss of acetylcholine receptor (AChR) expression,
      and a reduction in synaptic folds at the postsynaptic membrane in the absence of
      complement involvement. Failure of neuromuscular transmission at pre- and
      postsynaptic membranes of the NMJs has been observed in both patients and animal
      models of MuSK MG. A murine model of MuSK-MG revealed the mechanisms underlying
      cholinergic hypersensitivity after administration of acetylcholinesterase
      inhibitors, which has also been observed in MuSK-MG patients. Further studies of
      this model have provided evidence suggesting that 3,4-diaminopyridine may be
      effective as a symptomatic therapy for MuSK MG.

PMID- 23537507
TI  - Serological diagnostics in myasthenia gravis based on novel assays and recently
      identified antigens.
AB  - Myasthenia gravis (MG) is the most common immune-mediated disorder of the
      neuromuscular junction with a prevalence of 200-300/million population and its
      study has established paradigms for exploring other antibody-mediated diseases.
      Most MG patients (~85%) have autoantibodies against the muscle acetylcholine
      receptor (AChR-MG), whereas about 6% of MG patients have autoantibodies against
      the muscle specific kinase (MuSK-MG). Until recently no autoantibodies could be
      detected in the remaining patients (seronegative MG). Probably, the most
      sensitive assays for the detection of the autoantibodies in MG sera have been the
      radioimmunoprecipitation assays (RIPA) for both types of MG. However, with recent
      novel methods, not yet used routinely, it has been shown that the "seronegative"
      MG group includes patients with low levels of autoantibodies or of low affinity,
      against the known autoantigens, or even with antibodies to recently identified
      autoantigens. Since MG is heterogeneous in terms of pathophysiology, depending on
      the autoantigen targeted and on other factors (e.g. presence of thymoma), the
      serological tests are crucial in verifying the initial clinical diagnosis,
      whereas frequent measurement of autoantibody levels is important in monitoring
      the course of the disease and the efficacy of treatment. In addition, in AChR-MG,
      autoantibodies against the muscle proteins titin and ryanodin receptor have been
      identified; these antibodies are useful for the classification of MG, indicating
      the concomitant presence of thymoma, and as prognostic markers.

PMID- 23537508
TI  - Effect of stress on brain inflammation and multiple sclerosis.
AB  - Substantial evidence indicates that stress can precipitate or worsen symptoms of
      inflammation in general and more specifically in multiple sclerosis (MS), a
      demyelinating, autoimmune disease characterized by inflammation of the central
      nervous system (CNS). However, the mechanism of how stress affects MS is not well
      understood. We reviewed publications in PubMed since 1995 and propose that
      neuropeptides secreted under stress, such as corticotropin releasing hormone
      (CRH) and neurotensin (NT), activate microglia and mast cells to release
      inflammatory molecules. These lead to maturation and activation of T17 autoimmune
      cells, disruption of the blood-brain barrier (BBB) and T cell entry into the CNS,
      thus promoting brain inflammation and contributing to MS pathology. Reduction of
      stress and inhibition of these processes by select flavonoids could provide novel
      therapeutic approaches. 

PMID- 23537509
TI  - Ectopic germinal centers, BAFF and anti-B-cell therapy in myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disease mediated by antibodies directed
      to molecules of the endplate of the neuromuscular junction. B cells play a major
      role in MG disease since they produce the pathogenic antibodies and therapies
      targeting B cells are effective. The aim of this article was to review the role
      of B cells in myasthenia gravis. We will first describe what we know about B
      cells in this disease and examine the involvement of the B cells in the thymus of
      MG patients. We will detail the role of factors associated with B-cell function
      such as BAFF. Finally, we will discuss the effects of therapy targeting B cells.

PMID- 23537510
TI  - Complement associated pathogenic mechanisms in myasthenia gravis.
AB  - The complement system is profoundly involved in the pathogenesis of acetylcholine
      receptor (AChR) antibody (Ab) related myasthenia gravis (MG) and its animal model
      experimental autoimmune myasthenia gravis (EAMG). The most characteristic finding
      of muscle pathology in both MG and EAMG is the abundance of IgG and complement
      deposits at the nerve-muscle junction (NMJ), suggesting that AChR-Ab induces
      muscle weakness by complement pathway activation and consequent membrane attack
      complex (MAC) formation. This assumption has been supported with EAMG resistance
      of complement factor C3 knockout (KO), C4 KO and C5 deficient mice and
      amelioration of EAMG symptoms following treatment with complement inhibitors such
      as cobra venom factor, soluble complement receptor 1, anti-C1q, anti-C5 and anti
      C6 Abs. Moreover, the complement inhibitor decay accelerating factor (DAF) KO
      mice exhibit increased susceptibility to EAMG. These findings have brought
      forward improvisation of novel therapy methods based on inhibition of classical
      and common complement pathways in MG treatment.

PMID- 23537511
TI  - Effects of scalp dermatitis on chemical property of hair keratin.
AB  - The effects of scalp dermatitis (seborrheic dermatitis (SD), psoriasis, and
      atopic dermatitis (AD)) on chemical properties of hair keratin were investigated
      by Fourier transform infrared (FT-IR) spectroscopy. Hairs were collected from
      lesional regions affected by SD, psoriasis, and AD and non-lesional regions
      separately. The hairs with SD were taken from patients with ages of 16-80 years.
      The ages of patients with psoriasis ranged from 8 to 67 years, and all patients
      exhibited moderate disease. Hairs with AD were taken from the patients with ages
      of 24-45 years and the average SCORing atopic dermatitis (SCORAD) was 48.75.
      Hairs from 20 normal adults were collected as a control. The FT-IR absorbance
      bands were analyzed by the Gaussian model to obtain the center frequency, half
      width, height, and area of each band. The height and area of all bands in the
      spectra were normalized to the amide I centered at 1652 cm(-1) to quantitatively
      analyze the chemical composition of keratin. The spectra of hair with scalp
      dermatitis were different with that of control, the amide A components centered
      at 3278 cm(-1) were smaller than those of the control. The psoriasis hair showed
      a large difference in the IR absorbance band between lesional and non-lesional
      hairs indicating good agreement with the morphological changes. The hairs with
      diseases did not show differences in the content of cystine, which was centered
      at 1054 cm(-1), from the control. The chemical properties of keratin were not
      significantly different between the hairs affected by SD, psoriasis, and AD.
      However, the changes induced by scalp dermatitis were different with weathering.
      Therefore, FT-IR analysis could be used to screen differences between the
      physiological and pathological conditions of scalp hair.

PMID- 23537512
TI  - PlanktoVision--an automated analysis system for the identification of
      phytoplankton.
AB  - BACKGROUND: Phytoplankton communities are often used as a marker for the
      determination of fresh water quality. The routine analysis, however, is very time
      consuming and expensive as it is carried out manually by trained personnel. The
      goal of this work is to develop a system for an automated analysis. RESULTS: A
      novel open source system for the automated recognition of phytoplankton by the
      use of microscopy and image analysis was developed. It integrates the
      segmentation of the organisms from the background, the calculation of a large
      range of features, and a neural network for the classification of imaged
      organisms into different groups of plankton taxa. The analysis of samples
      containing 10 different taxa showed an average recognition rate of 94.7% and an
      average error rate of 5.5%. The presented system has a flexible framework which
      easily allows expanding it to include additional taxa in the future. CONCLUSIONS:
      The implemented automated microscopy and the new open source image analysis
      system--PlanktoVision--showed classification results that were comparable or
      better than existing systems and the exclusion of non-plankton particles could be
      greatly improved. The software package is published as free software and is
      available to anyone to help make the analysis of water quality more reproducible
      and cost effective.

PMID- 23537513
TI  - Quantum mechanical characterization of the He4ICl weakly bound complex.
AB  - Vibrational calculations are performed for the 12-dimensional He4ICl van der
      Waals complex using the multiconfiguration time-dependent Hartree (MCTDH) method.
      The potential energy surface of the cluster is represented as a sum of the
      triatomic He-ICl ab initio parametrized terms plus the He-He interactions. The
      topology of the potential presents higher anisotropy compared to the one with a
      homonuclear dopant, and this is clearly reflected in the structure and energetics
      of the low-lying conformers of the system. In order to take advantage of the
      MCTDH method, natural potential fits are employed for the potential energy
      operator, and also, a mode combination scheme is introduced in order to speed up
      the computations. Zero-point energy, binding energies, and vibrationally averaged
      structures of different isomers of the He4ICl cluster are obtained. The present
      results predict that the (3,1,0) structure, involving three He atoms in the near
      T-shaped and one He atom in the linear configurations, to be the most stable one
      in accord with recent experimental findings. Comparisons with previous
      theoretical and experimental data are presented, and the stability of the high
      order conformers is discussed in connection with the multiple minima (global and
      local) of the underlying potential surface. 

PMID- 23537514
TI  - Rice protein ameliorates the progression of diabetic nephropathy in Goto-Kakizaki
      rats with high-sucrose feeding.
AB  - The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous
      type 2 diabetic Goto-Kakizaki (GK) rats was investigated.GK rats at 7 weeks of
      age were fed 20% RP or casein (C) in standard or high-sucrose diets for 10 weeks.
      Plasma total cholesterol,TAG, alkaline phosphatase (ALP), adiponectin, creatinine
      and urinary albumin excretion (UAE) were measured and renal histology was
      evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin
      levels in GK rats fed the standard diet (P<0.05), and also lowered total
      cholesterol and ALP in high-sucrose-fed GK rats (P<0.05). RP markedly suppressed
      the sharp increase in UAE when GK rats were fed high-sucrose diets (P<0.05), and
      prevented glomerular mesangial matrix expansion in the deep renal cortex near the
      corticomedullary junction (P<0.05). These results strongly indicate that dietary
      RP can ameliorate the progression of diabetic nephropathy at an early stage
      compared with C.

PMID- 23537515
TI  - The evolution of host associations in the parasitic wasp genus Ichneumon
      (Hymenoptera: Ichneumonidae): convergent adaptations to host pupation sites.
AB  - BACKGROUND: The diversification of organisms with a parasitic lifestyle is often
      tightly linked to the evolution of their host associations. If a tight host
      association exists, closely related species tend to attack closely related hosts;
      host associations are less stable if associations are determined by more plastic
      traits like parasitoid searching and oviposition behaviour. The pupal-parasitoids
      of the genus Ichneumon attack a variety of macrolepidopteran hosts. They are
      either monophagous or polyphagous, and therefore offer a promissing system to
      investigate the evolution of host associations. Ichneumon was previously divided
      into two groups based on general body shape; however, a stout shape has been
      suggested as an adaptation to buried host pupation sites, and might thus not
      represent a reliable phylogenetic character. RESULTS: We here reconstruct the
      first molecular phylogeny of the genus Ichneumon using two mitochondrial (CO1 and
      NADH1) and one nuclear marker (28S). The resulting phylogeny only supports
      monophyly of Ichneumon when Ichneumon lugens Gravenhorst, 1829 (formerly in
      Chasmias, stat. rev.) and Ichneumon deliratorius Linnaeus, 1758 (formerly
      Coelichneumon) are included. Neither parasitoid species that attack hosts
      belonging to one family nor those attacking butterflies (Rhopalocera) form
      monophyletic clades. Ancestral state reconstructions suggest multiple transitions
      between searching for hosts above versus below ground and between a stout versus
      elongated body shape. A model assuming correlated evolution between the two
      characters was preferred over independent evolution of host-searching niche and
      body shape. CONCLUSIONS: Host relations, both in terms of phylogeny and ecology,
      evolved at a high pace in the genus Ichneumon. Numerous switches between hosts of
      different lepidopteran families have occurred, a pattern that seems to be the
      rule among idiobiont parasitoids. A stout body and antennal shape in the
      parasitoid female is confirmed as an ecological adaptation to host pupation sites
      below ground and has evolved convergently several times. Morphological characters
      that might be involved in adaptation to hosts should be avoided as diagnostic
      characters for phylogeny and classification, as they can be expected to show high
      levels of homoplasy.

PMID- 23537516
TI  - Differences in youth and adult physical activity in park settings by sex and
      race/ethnicity.
AB  - We examined differences by sex and race/ethnicity in the observed moderate- to
      vigorous-intensity physical activity (MVPA) of youth and adults in diverse areas
      of 4 parks in Kansas City, Missouri, in 2009. Male youth were more active on
      playgrounds and pools or splashpads than female youth. White youth were less
      active than nonwhite youth in open spaces and on paved trails. Male adults were
      more active in open spaces than female adults, and white adults were more active
      on paved trails than nonwhite adults. Understanding variations in MVPA between
      user groups can inform park design efforts to foster increased activity among all
      visitors.

PMID- 23537517
TI  - High prevalence of diabetes among Indo-Guyanese adults, Schenectady, New York.
AB  - INTRODUCTION: The Indo-Guyanese population is the largest immigrant minority
      population in Schenectady, New York. A clinic-based study in Schenectady and
      surveillance reports from Guyana found high diabetes prevalence and mortality
      among Guyanese of Indian descent. No community-based study has focused on
      diabetes among Indo-Guyanese immigrants in the United States. We sought
      information on the prevalence of diabetes and its complications in Indo-Guyanese
      adults in Schenectady and compared it with the prevalence among non-Hispanic
      white adults in Schenectady. METHODS: We administered a cross-sectional health
      survey at community venues in Schenectady in 2011. We identified diagnosed
      diabetes and its complications through self-reports by using a reliability-tested
      questionnaire. The final data set included 313 Indo-Guyanese and 327 non-Hispanic
      white adults aged 18 years or older. We compared the prevalence of diagnosed
      diabetes and diabetes complications between Indo-Guyanese and non-Hispanic
      whites. RESULTS: Most Indo-Guyanese participants were born in Guyana, whereas
      most non-Hispanic whites were born in the United States. The crude prevalence of
      diagnosed diabetes among Indo-Guyanese participants and non-Hispanic whites was
      30.3% and 16.1%, respectively. The age-standardized prevalence was 28.7% among
      Indo-Guyanese participants, significantly higher than that among non-Hispanic
      whites (14.5%, P < .001). Indo-Guyanese participants who had diabetes had a lower
      body mass index and were more likely to report poor or fair general health and
      eye or vision complications than non-Hispanic whites who had diabetes.
      CONCLUSION: Our study confirms the higher prevalence of diabetes in Indo-Guyanese
      adults in Schenectady. The higher prevalence of complications suggests poor
      control of diabetes. Excess burden of diabetes in this population calls for
      further research and public health action.

PMID- 23537518
TI  - HPV Knowledge Among a Marginalized Population [Letter].

PMID- 23537519
TI  - Sociodemographic and health-related risk factors associated with tooth loss among
      adults in Rhode Island.
AB  - INTRODUCTION: Oral health is an integral component of overall health and well
      being. Very little Rhode Island state-level information exists on the
      determinants of tooth loss. The objective of this study was to systematically
      identify sociodemographic characteristics, health behaviors, health conditions
      and disabilities, and dental insurance coverage associated with tooth loss among
      noninstitutionalized adults in Rhode Island. METHODS: We analyzed Rhode Island's
      2008 and 2010 Behavioral Risk Factor Surveillance System survey data in 2011. The
      survey had 4 response categories for tooth loss: none, 1 to 5, 6 or more but not
      all, and all. We used multinomial logistic regression models to assess the
      relationship between 4 risk factor domains and tooth loss. RESULTS: An estimated
      57.6% of Rhode Island adults had all their teeth, 28.9% had 1 to 5 missing teeth,
      8.9% had 6 to 31 missing teeth, and 4.6% were edentulous. Respondents who had low
      income, low education, unhealthy behaviors (ie, were former or current smokers
      and did not engage in physical activity), chronic conditions (ie, diabetes and
      obesity) or disabilities, and no dental insurance coverage were more likely to
      have fewer teeth compared with their referent groups. However, the association of
      these variables with tooth loss was not uniform by age group. CONCLUSION: Adults
      who report risky health behaviors or impaired health may be considered target
      subpopulations for prevention of tooth loss and promotion of good oral health.

PMID- 23537520
TI  - Association KRAS G13D tumor mutated outcome in patients with chemotherapy
      refractory metastatic colorectal cancer treated with cetuximab.
AB  - BACKGROUND/AIMS: Cetuximab is currently approved for the treatment of metastatic
      colorectal cancer (mCR) with KRAS wild-type. Prior few studies demonstrated that
      G13D mutated tumors could benefit from cetuximab. This study aims to investigate
      whether KRAS G13D mutated tumors benefit from cetuximab in the chemotherapy
      refractory patients. METHODOLOGY: We retrospectively compared progression-free
      survival (PFS), overall survival (OS) and response rate (RR) according to KRAS
      mutation status in 105 patients with mRC treated at the Cerrahpasa Medical School
      Hospital, between October 2008 and October 2011, with cetuximab alone or in
      combination with chemotherapy. RESULTS: PFS was significantly longer in patients
      G13D mutated tumors (6.81 months) than in patients with other KRAS mutated tumors
      (5 months) (p=0.027). No significant difference in PFS between patients G13D
      mutated and KRAS wild-type tumors was detected. No significant difference in OS
      was detected in patients between G13D mutated tumors and other KRAS mutated
      tumors. However, patients with KRAS wild-type tumors had significantly longer OS
      (16.1 months) than patients with mutated tumors (8.9 months) (p=0.025). RR in
      patients with other KRAS mutated tumors, was significantly worse than those with
      G13D mutated tumors (p=0.002). CONCLUSION: Our study demonstrated an association
      between the presence KRAS G13D mutanted and survival chemotherapy in refractory
      metastatic colorectal cancer treated with cetuximab.

PMID- 23537521
TI  - Severe back pain and lower extremities weakness in a young male.

PMID- 23537522
TI  - Effects of resveratrol on changes induced by high-fat feeding on clock genes in
      rats.
AB  - In mammals, the main component of the circadian system is the suprachiasmatic
      nucleus in the hypothalamus. However, circadian clocks are also present in most
      peripheral tissues, such as adipose tissue. The aim of the present study was to
      analyse the potential effects of resveratrol on changes induced by high-fat
      feeding in the expression of clock genes and clock-controlled genes in the white
      adipose tissue from rats. For this purpose, rats were divided into three groups:
      a control group, fed a standard diet, and two other groups, either fed a high-fat
      diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression
      of clock genes and clock-controlled genes was analysed by RT-PCR. Protein
      expression and fatty acid synthase (FAS) activity were also analysed. When
      comparing the controls, the RSV group showed similar patterns of response to the
      HF group, except for reverse erythroblastosis virus alpha (Rev-Erbalpha), which
      was down-regulated. The expression of this gene reached the same levels as in
      control rats. The response pattern of protein expression for Rev-Erbalpha was
      similar to that found for gene expression. High-fat feeding up-regulated all
      adipogenic genes and resveratrol did not modify them. In the HF group, the
      activity of FAS tended to increase, while resveratrol decreased. In conclusion,
      resveratrol reverses the change induced by high-fat feeding in the expression of
      Rev-Erbalpha in adipose tissue, which means that clock machinery is a target for
      this polyphenol. This change seems to be related to reduced lipogenesis, which
      might be involved in the body fat-lowering effect of this molecule. 

PMID- 23537523
TI  - Availability of haematopoietic niches for transplanted stem cells.
AB  - Following transplantation, donor haematopoietic stem cells (HSCs) must reach
      specific parts of haematopoietic stroma tissue known as stem cell niches to
      become engrafted and to start blood cell production. Regularly, they have to
      compete with the host's HSCs for a limited number of niches. The exact mechanisms
      of HSC engraftment as well as of niche "opening" to incoming HSCs by conditioning
      treatments are not well-known yet. Significant and stable engraftment of
      syngeneic donor HSCs can be achieved in untreated mice only after transplantation
      of very large numbers of marrow cells. Engraftment can be largely facilitated by
      the stem cell mutations reducing numbers of the host HSCs. Pre-transplantation
      manipulations of the host haematopoietic tissue enhance engraftment depending on
      how much they damage HSCs. Ionizing radiation appears to be the most effective in
      this respect despite proliferative quiescence of a majority of HSCs. The review
      summarizes major achievements in deciphering biological principles of the HSCs
      and their engraftment after transplantation obtained in experimental research
      studying murine haematopoiesis.

PMID- 23537524
TI  - Proteinuria and hypertension in patients treated with inhibitors of the VEGF
      signalling pathway--incidence, mechanisms and management.
AB  - Anti-VEGF therapy dramatically improved the outcome of patients with renal cancer
      and other advanced malignancies, but may be complicated by proteinuria and
      hypertension. VEGF is indispensable for the normal development of glomerulus and
      preservation of glomerular filtration barrier. Interference with its action may
      result in damage to glomerular endothelial cells and (in severe cases) in renal
      thrombotic microangiopathy. Blood pressure and proteinuria (using dipstick)
      should be assessed in all patients before starting anti-VEGF therapy and
      regularly monitored during the treatment. Patients with severe proteinuria and/or
      impaired renal function should be referred to the nephrologist for further work
      up. Hypertension caused by anti-VEGF therapy can be effectively treated;
      progression of proteinuria and/or renal dysfunction may require tapering, or even
      withdrawal of anti-VEGF treatment.

PMID- 23537525
TI  - In vivo growth of mantle cell lymphoma xenografts in immunodeficient mice is
      positively regulated by VEGF and associated with significant up-regulation of
      CD31/PECAM1.
AB  - Mantle cell lymphoma (MCL) is an aggressive lymphoma subtype with dismal
      prognosis. New treatments are needed to improve outcome of relapsed/ refractory
      disease. Recently, several drugs targeting at least partially the process of
      angiogenesis have been successfully tested in the therapy of MCL. Molecular
      mechanisms that regulate MCL-induced angiogenesis and that might represent
      potential new druggable targets remain, however, incompletely understood. We
      established two mouse models of human MCL by subcutaneous xenotransplantation of
      JEKO-1 and HBL-2 cell lines into immunodeficient mice. Histological analyses of
      xenografts confirmed their neovascularization. The growth of xenografts was
      significantly suppressed by single-agent therapy with bevacizumab, monoclonal
      antibody targeting vascular endothelial growth factor (VEGF). Subsequently, we
      analysed expression of 94 angiogenesis related genes in ex vivo isolated JEKO-1
      and HBL-2 cells compared to in vitro growing cells using TaqMan low-density
      arrays. The most up-regulated genes in both JEKO-1 and HBL-2 xenografts were
      genes encoding platelet/endothelial cell-adhesion molecule (CD31/PECAM1), VEGF
      receptor 1 (FLT1), hepatocyte growth factor (HGF), angiogenin (ANG) and
      transcription factor PROX1. The most downregulated genes in both JEKO-1 and HBL-2
      xenografts were midkine (MDK) and ephrine B2 (EPHB2). In summary, our results
      demonstrate an important role of angiogenesis in the biology of MCL and provide
      preclinical evidence of potent anti-MCL activity of bevacizumab. In addition,
      gene expression profiling of 94 angiogenesis-related targets revealed several in
      vivo up-regulated and down-regulated transcripts. The most differentially
      expressed target in both MCL tumours was CD31/PECAM1. Whether any of these
      molecules might represent a potential druggable target in MCL patients remains to
      be elucidated.

PMID- 23537526
TI  - Galantamine as a preventive of diisopropylphosphorofluoridate toxicity effects in
      rat brain.
AB  - Diisopropylfluorophosphate exerts its toxic effect by irreversibly inhibiting
      acetylcholinesterase. This results in over-stimulation of central and peripheral
      cholinergic activity. The aim of the present study was to evaluate the possible
      preventive effects of acute treatment with reversible acetylcholinesterase
      inhibitor galantamine against the signs of cholinergic toxic syndrome provoked by
      diisopropylfluorophosphate, such as hypothermia, muscular fasciculations, oral
      dyskinesia and decreased locomotor performance in a rat model of intoxication.
      The effects of these two anticholinesterases on acetylcholinesterase activity and
      on the expression of mRNA of the immediate early response gene c-fos in the brain
      were assessed by histochemical acetylcholinesterase staining and by in situ
      hybridization, respectively. Diisopropylfluorophosphate induced rapidly
      progressing hypothermia, muscular fasciculations, oral dyskinesia and decreased
      locomotor performance. The increased cholinergic cortical and hippocampal
      activity due to irreversible acetylcholinerase inhibition were indicated by the
      increased c-fos mRNA autoradiographic signal and by the inhibition of
      acetylcholinesterase staining, respectively. Galantamine by itself provoked
      transient and relatively weak inhibition of the acetylcholinesterase staining,
      while it did not induce increased c-fos mRNA expression or significant
      behavioural signs of cholinergic toxicity. Galantamine significantly reduced the
      rate of the onset, but not the maximal hypothermia induced by
      diisopropylfluorophosphate. Importantly, all the above-mentioned behavioural and
      neurochemical effects of diisopropylfluorophosphate were significantly reduced by
      galantamine. These results indicate that the acute pre-treatment with galantamine
      may have prophylactic effects against the intoxication by
      diisopropylfluorophosphate.

PMID- 23537527
TI  - Rapid isolation of lysosomal membranes from cultured cells.
AB  - We present a simple method for enrichment of lysosomal membranes from HEK293 and
      HeLa cell lines taking advantage of selective disruption of lysosomes by
      methionine methyl ester. Organelle concentrate from postnuclear supernatant was
      treated with 20 mmol/l methionine methyl ester for 45 min to lyse the lysosomes.
      Subsequently, lysosomal membranes were resolved on a step sucrose gradient. An
      enriched lysosomal membrane fraction was collected from the 20%/35% sucrose
      interface. The washed lysosomal membrane fraction was enriched 30 times relative
      to the homogenate and gave the yield of more than 8%. These results are
      comparable to lysosomal membranes isolated by magnetic chromatography from
      cultured cells (Diettrich et al., 1998). The procedure effectively eliminated
      mitochondrial contamination and minimized contamination from other cell
      compartments. The enriched fractions retained the ability to acidify membrane
      vesicles through the activity of lysosomal vacuolar ATPase. The method avoids non
      physiological overloading of cells with superparamagnetic particles and appears
      to be quite robust among the tested cell lines. We expect it may be of more
      general use, adaptable to other cell lines and tissues.

PMID- 23537528
TI  - Validation of RNA extraction procedures focused on micro RNA expression analysis.
AB  - The sampling procedure is a crucial step in every kind of experiment. This is
      also true in gene expression profiling experiments, where high quality and
      sufficient quantity of extracted RNA plays a significant role in the experimental
      outcome. We have compared five different RNA extraction protocols from peripheral
      blood/PBMCs with the aim to define the most suitable method for the miRNA
      expression profiling experiments. Convincing results in terms of highest quantity
      and quality were obtained by the TRIzol-chloroform extraction method. The total
      RNA obtained using this method contained the highest portion of good-quality
      miRNA molecules, which was also confirmed by gene-specific real-time PCR
      experiments.

PMID- 23537529
TI  - Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in
      senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells.
AB  - Recently, the ability of polyphenols to reduce the risk of dementia and
      Alzheimer's disease (AD) has attracted a great deal of interest. In the present
      study, we investigated the attenuating effects of oligomerised lychee fruit
      derived polyphenol (OLFP, also called Oligonol) on early cognitive impairment.
      Male senescence-accelerated mouse prone 8 (SAMP8) mice (4 months old) were given
      OLFP (100 mg/kg per d) for 2 months, and then conditioned fear memory testing was
      conducted. Contextual fear memory, which is considered hippocampus-dependent
      memory, was significantly impaired in SAMP8 mice compared with non-senescence
      accelerated mice. OLFP attenuated cognitive impairment in SAMP8 mice. Moreover,
      the results of real-time PCR analysis that followed DNA array analysis in the
      hippocampus revealed that, compared with SAMP8 mice, the mRNA expression of
      Wolfram syndrome 1 (Wfs1) was significantly higher in SAMP8 mice administered
      with OLFP. Wfs1 reportedly helps to protect against endoplasmic reticulum (ER)
      stress, which is thought to be one of the causes for AD. The expression of Wfs1
      was significantly up-regulated in NG108-15 neuronal cells by the treatment with
      OLFP, and the up-regulation was inhibited by the treatment of the cells with a c
      Jun N-terminal kinase-specific inhibitor rather than with an extracellular signal
      regulated kinase inhibitor. Moreover, OLFP significantly attenuated the
      tunicamycin-induced expression of the ER stress marker BiP (immunoglobulin heavy
      chain-binding protein) in the cells. These results suggest that OLFP has an
      attenuating effect on early cognitive impairment in SAMP8 mice, and diminishes ER
      stress in neuronal cells.

PMID- 23537530
TI  - Is verbal episodic memory in elderly with amyloid deposits preserved through
      altered neuronal function?
AB  - A potential mechanism that enables intellectual preservation in cognitively
      normal elderly that harbor beta-amyloid (Abeta) pathology is heightened cerebral
      glucose metabolism. To investigate cross-sectional inter-relationships between
      Abeta, glucose metabolism, and cognition, 81 subjects (mean age: 75 +/- 7 years)
      underwent [(11)C]Pittsburgh Compound-B and [(18)F]fluorodeoxyglucose positron
      emission tomography scans and neuropsychological testing. They were divided into
      low-Abeta (n = 53), intermediate-Abeta (n = 13) and high-Abeta (n = 15) groups as
      defined by their global cortical [(11)C]PIB retention. Glucose metabolism was
      assessed using a MetaROI mask that covers metabolically critical regions in
      Alzheimer's disease (AD) (i.e., posterior cingulate and bilateral angular and
      inferior temporal gyri). Previously validated factor scores for verbal and visual
      episodic memory, semantic memory, working memory, and executive functioning were
      used to evaluate cognitive performances. Greater Abeta deposition in the
      precuneus was associated with higher metabolic activity (at trend level) and
      lower visual episodic memory scores. Glucose metabolism did not correlate with
      cognition across all subjects. However, heightened metabolic activity was
      associated with better verbal episodic memory performance in subjects with
      elevated amyloid levels. This preliminary study suggests that neural
      compensation, as a manifestation of brain reserve, enables elderly supposedly on
      the path to AD, at least temporarily, to preserve cognitive function.

PMID- 23537532
TI  - [Application progress of endobronchial ultrasound].

PMID- 23537533
TI  - [Electromagnetic navigation bronchoscopy: new progress of clinical application].

PMID- 23537531
TI  - DOC2B and Munc13-1 differentially regulate neuronal network activity.
AB  - Alterations in the levels of synaptic proteins affect synaptic transmission and
      synaptic plasticity. However, the precise effects on neuronal network activity
      are still enigmatic. Here, we utilized microelectrode array (MEA) to elucidate
      how manipulation of the presynaptic release process affects the activity of
      neuronal networks. By combining pharmacological tools and genetic manipulation of
      synaptic proteins, we show that overexpression of DOC2B and Munc13-1, proteins
      known to promote vesicular maturation and release, elicits opposite effects on
      the activity of the neuronal network. Although both cause an increase in the
      overall number of spikes, the distribution of spikes is different. While DOC2B
      enhances, Munc13-1 reduces the firing rate within bursts of spikes throughout the
      network; however, Munc13-1 increases the rate of network bursts. DOC2B's effects
      were mimicked by Strontium that elevates asynchronous release but not by a DOC2B
      mutant that enhances spontaneous release rate. This suggests for the first time
      that increased asynchronous release on the single-neuron level promotes bursting
      activity in the network level. This innovative study demonstrates the
      complementary role of the network level in explaining the physiological relevance
      of the cellular activity of presynaptic proteins and the transformation of
      synaptic release manipulation from the neuron to the network level. 

PMID- 23537534
TI  - [Does transbronchial needle aspiration need endobronchial ultrasound-guide?].

PMID- 23537535
TI  - [Endobronchial ultrasonography for the diagnosis of peripheral pulmonary
      lesions].

PMID- 23537536
TI  - [Non-real-time endobronchial bronchoscopy ultrasound assisted transbronchial lung
      biopsy in diagnosing peripheral pulmonary lesions].
AB  - OBJECTIVE: To evaluate the role of non-real-time endobronchial bronchoscopy
      ultrasound(EBUS) assisted transbronchial lung biopsy (TBLB) in diagnosing
      peripheral pulmonary lesions (PPL). METHODS: One hundred and five patients [68
      males and 37 females, mean age (59 +/- 12) years, ranged from 39 - 81 years] with
      PPL confirmed by computered tomography (CT) were recruited in this study between
      June 1st 2011 and March 1st 2012. All cases received bronchoscopy examinations
      and presented with roughly normal results. Fifty-four cases received EBUS
      examinations. For peripheral lesions with accessible EBUS images, blind biopsy
      was performed with biopsy forceps through pathways of the ultrasonic probe after
      the retreat of the probe. In those cases without accessible EBUS images, blind
      biopsy was performed based on the localization by image data. The other 51 cases
      without EBUS testing underwent blind biopsy on the localization by image data.
      Positive rates of pathological diagnosis of the 2 groups were compared. Analysis
      was by chi(2)-test. RESULTS: In 54 patients who received EBUS examinations, 76%
      (41/54) of PPLs were detected performed by EBUS. The positive rate of the EBUS
      assisted TBLB group was 67% (36/54), compared with 45% (23/51) in the general
      TBLB group. There was a better diagnostic rate (P < 0.05) in the EBUS assisted
      TBLB group than the general TBLB group. Thirteen patients without accessible EBUS
      images obtained negative pathological results. The diagnosis rate of EBUS
      assisted TBLB on lesions with <= 30 mm minimum diameter was 44% (8/18), lower
      than 78% (28/36) on lesions with > 30 mm minimum diameter (P < 0.05). In terms of
      diagnosis rate on lesions with <= 30 mm minimum diameter, EBUS assisted TBLB was
      44% (8/18), higher than 12% (2/17) of TBLB alone (P < 0.05). As for lesions with
      > 30 mm minimum diameter, diagnosis rate of EBUS assisted TBLB was 52% (28/54)
      and TBLB alone was 41% (21/51), representing insignificant difference (P > 0.05).
      In the EBUS assisted TBLB group, we performed 269 blind biopsies, with an average
      of 4.8 times per case, whereas the general TBLB group required 398 times, with an
      average of 7.8 times per case. EBUS assisted TBLB decreased the operation times
      of blind biopsy (P < 0.05) to acquire adequate and appropriate specimen.
      Complications of biopsy occurred in this study included slight haemoptysis
      (61/105, 58.1%), chest pain (25/105, 23.8%) and pneumothorax (2/105, 1.9%).
      Patients with these complications recovered spontaneously without special
      managements. CONCLUSIONS: Non-real-time EBUS assisted TBLB could improve
      diagnostic positive rate without increasing operational risk. In most cases, the
      blind biopsy did not succeed if EBUS failed to detect the lesions. The success
      rate of non-real-time EBUS assisted TBLB was related to the minimum diameter of
      PPL. In terms of diagnosis rate on lesions with <= 30 mm minimum diameter, EBUS
      assisted TBLB was higher than TBLB alone. As for lesions with >30mm minimum
      diameter, there was no significant difference in the diagnosis rate between these
      2 groups. EBUS assisted TBLB decreased the times of blind biopsy process (P <
      0.05) to obtain adequate and appropriate specimen.

PMID- 23537537
TI  - [Endobronchial ultrasound-guided transbronchial needle aspiration in the
      diagnosis of intrapulmonary lesions].
AB  - OBJECTIVE: To evaluate real-time endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) in the diagnosis of intrapulmonary lesions.
      METHODS: From October 2009 to November 2011, EBUS-TBNA was performed in 78
      patients with parabrachial or parabronchial intrapulmonary lesions proved by CT
      scan. On-site cytological evaluation was not performed. Immunohistochemistry was
      applied to distinguish the type of malignant tumor when necessary. RESULTS: Sixty
      five malignancies and 13 benign diseases were finally diagnosed in 78
      intrapulmonary lesions, of which 62 malignancies and 13 benign diseases were
      distinguished by EBUS-TBNA, including 61 primary lung cancer (adenocarcinoma 36,
      squamous carcinoma 8, poorly-differentiated carcinoma 5, unknown type carcinoma
      3, small cell carcinoma 9), one metastatic lung cancer, 7 pulmonary inflammation,
      5 pulmonary tuberculosis and one fibrosis. There were 3 false negative cases
      which were diagnosed as pulmonary poorly-differentiated carcinoma, pulmonary
      sarcomatoid carcinoma and pulmonary lymphoma, respectively. Sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      EBUS-TBNA in distinguishing malignant from benign thoracic lesions was 95%, 100%,
      81%, 100%, 96%, respectively. Immunohistochemistry was performed in 8 malignant
      tumors without definite type or origin, 5 primary lung cancer and one metastatic
      lung adenocarcinoma were further confirmed. Moderate bleeding from the puncture
      site during needle aspiration forming blood clot and obstructing the central
      airway was noted in 1 hypercoagulable subject. CONCLUSIONS: EBUS-TBNA is a
      minimally invasive, safe procedure with high sensitivity for distinguishing
      malignant from benign lesions. Immunohistochemistry can provide evidence for the
      definitive diagnosis of malignant lesions.

PMID- 23537538
TI  - [Evaluation of endobronchial ultrasound-guided transbronchial needle aspiration
      in the diagnosis of hilar and mediastinal tumors].
AB  - OBJECTIVE: To explore the diagnostic values of endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) in patients with hilar and
      mediastinal tumors. METHODS: A total of 837 patients with chest CT or PET/CT
      confirmed mediastinal/hilar lymphadenopathy and or tumors in (or around) the
      trachea or bronchi, were evaluated by EBUS-TBNA examination. Pathological study
      or follow-up visit was carried out in the same period to make a final diagnosis,
      and therefore to verify the accuracy of EBUS-TBNA. RESULT: The study punctured
      1631 lymph nodes totally, with an average of 1.95 times per case. The 4R group
      and the 7th group of lymph nodes accounted for 43% and 34%, respectively. The
      success rate of TBNA was 100%. The diagnosis rates of lung cancer was 94.11%, of
      which squamous cell carcinoma accounted for 19.22% (89 cases), adenocarcinoma
      32.40% (150 cases), small cell carcinoma 23.54% (109 cases), non-small cell
      carcinoma of unknown histological type 9.50% (44 cases), adenosquamous carcinoma
      7.56% (35 cases), and other types 7.78% (36 cases). The diagnosis rate of
      tuberculosis was 85.50%, and that of sarcoidosis was 55.88%. The overall
      sensitivity of EBUS-TBNA was 94.02%, specificity 100%, positive predictive value
      100%, negative predictive value 61.91%, and the accuracy was 94.56%. Besides mild
      bleeding in the puncture site, no other complications occurred, and there were no
      severe complications such as pneumothorax, pneumomediastinum, or major vascular
      injury. CONCLUSION: EBUS-TBNA is of high value as a minimally invasive,
      convenient, and low-risk procedure for the diagnosis of mediastinal and hilar
      lymphadenopathy and tumors.

PMID- 23537539
TI  - [The role of endotracheal aspirate culture in the diagnosis of ventilator
      associated pneumonia: a meta analysis].
AB  - OBJECTIVE: To investigate the role of endotracheal aspirate (EA) culture in the
      diagnosis and antibiotic management in ventilator-associated pneumonia (VAP).
      METHODS: We searched CNKI, Wanfang, PUBMED and EMBASE databases published from
      January 1990 to December 2011, to find relevant literatures on VAP
      microbiological diagnostic techniques including EA and bronchoalveolar lavage
      (BALF). The following key words were used: ventilator associated pneumonia,
      diagnosis and adult. Meta-analysis was performed and the sensitivity and
      specificity of EA on VAP diagnosis were calculated. RESULTS: Our literature
      search identified 1665 potential articles, 8 of which fulfilled our selection
      criteria including 561 patients with paired cultures. Using BALF quantitative
      culture as reference standard, the sensitivity and specificity of EA were 72% and
      71%. When considering quantitative culture of EA only, the sensitivity and
      specificity improved to 90% and 65%, while the positive and the negative
      predictive values were 68% and 89% respectively. However, the sensitivity and
      specificity of semi-quantitative culture of EA were only 50% and 80%, with a
      positive predictive value of 77% and a negative predictive value of 58%
      respectively. CONCLUSIONS: EA culture had relatively poor sensitivity and
      specificity, although quantitative culture of EA only could improve the
      sensitivity. Initiating therapy on the basis of EA quantitative culture may still
      result in excessive antibiotic usage. Our data suggested that EA could provide
      some information for clinical decision but could not replace the role of BALF
      quantitative culture in VAP diagnosis.

PMID- 23537540
TI  - [Tumor necrosis factor alpha-238G/A polymorphism and tuberculosis susceptibility:
      a meta-analysis].
AB  - OBJECTIVE: A comprehensive meta-analysis was performed to investigate the
      relationship between TNF -238G/A polymorphism and tuberculosis susceptibility.
      METHODS: Tuberculosis, TB, mycobacteria, polymorphism, variant, mutation,
      susceptibility, tumor necrosis factor or, TNF, cytokine, and gene were used as
      key words both in Chinese and English to search all the published related
      articles in Pubmed, Embase, Web of science, Science Direct, Springer Link, EBSCO,
      Wanfang and Chinese Journal Full-text Database until October 2011. HWE test was
      performed in all the comparisons. Heterogeneity across studies was determined,
      and sensitivity analyses were conducted. RESULTS: Nine case-control studies were
      included. The meta-analysis indicated that there was no significant association
      between TNF -238G/A polymorphism and tuberculosis susceptibility (GA + AA vs GG
      model: OR = 1.00, 95%CI: 0.77 - 1.32; A vs G model: OR = 1.00, 95%CI: 0.77 -
      1.30). No significant heterogeneity (Q was 5.04 and 5.82 respectively, P > 0.05)
      and publication bias (GA + AA vs GG model: Begg test Z = 0.73, Egger test t =
      1.94, P > 0.05; A vs G model: Begg test Z = 0.52, Egger test t = 1.72, P > 0.05)
      were demonstrated. Sensitivity analyses further indicated the reliability of the
      study (OR were 0.94 - 1.10 respectively, all P > 0.05). CONCLUSION: Our study did
      not detect any association between TNF -238G/A polymorphism and tuberculosis
      susceptibility.

PMID- 23537541
TI  - [Association of genetic polymorphisms of angiotensin converting enzyme and matrix
      metallo proteinase-1 with idiopathic pulmonary fibrosis].
AB  - OBJECTIVE: To investigate the correlation between angiotensin converting enzyme
      (ACE) and matrix metallo proteinase (MMP)-1 gene polymorphisms and the risk of
      idiopathic pulmonary fibrosis (IPF) in a Han Chinese population from Hebei
      Province. METHODS: Eighty-four IPF patients and 100 controls were enrolled from
      the Second Hospital of Hebei Medical University. Polymerase chain reaction (PCR)
      and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      were used to detect ACE gene insertion/deletion (I/D) polymorphism and MMP-1
      polymorphism respectively. The MMP-1 polymorphism was genotyped by DNA sequence
      analysis. Radioimmunoassay and ELISA were used to analyzed AngII, MMP-1 and TIMP
      1 levels in IPF patients and healthy controls. RESULTS: There was a significant
      difference between the 2 groups in allele and genotype frequency distribution of
      ACE Insertion/Deletion polymorphism; frequency distribution of DD genotype and D
      allele of IPF patients were higher than those of the healthy control group
      (chi(2) = 11.227, 4.318, P < 0.05). There was no difference from different
      genders and ages on allele and genotype frequency distribution of ACE
      Insertion/Deletion polymorphism. (chi(2) = 0.03 - 1.069, P > 0.05). There was no
      significant difference between the 2 groups in genotype and allele frequency
      distribution of MMP-1 1G/2G polymorphism (chi(2) = 0.94 and 0.001, P > 0.05). The
      AngII levels from DD genotype of both IPF patients and healthy controls were the
      highest, followed by the DI genotype and the II genotype. The AngII level of any
      genotype for ACE Insertion/Deletion polymorphism in the IPF group was higher than
      that in the healthy control group (all P < 0.05). The serum level of AngII, MMP-1
      and TIMP-1, as well as MMP-1/TIMP-1 ratio in the IPF group were higher than those
      in the healthy control group (all P < 0.05). CONCLUSIONS: The ACE polymorphism
      might be associated with IPF, and the serum level of AngII was affected not only
      by the genetic background of ACE insertion/deletion polymorphism but also the
      environmental factors. The MMP-1 1G/2G polymorphism might be weakly associated
      with IPF.

PMID- 23537542
TI  - [Advances in the application of interferon gamma release assay in controlling
      tuberculosis group infection].

PMID- 23537543
TI  - [Advances in immunologic mechanisms of lung inflammation induced by airborne
      particulate matter].

PMID- 23537544
TI  - [Progress in pathogenic mechanism of PM2.5 and its prevention].

PMID- 23537545
TI  - [The research progress of epidermal growth factor receptor tyrosine kinase
      inhibitor in pulmonary fibrosis].

PMID- 23537546
TI  - Galectin-3, new potential therapeutic target for cardiac remodelling.

PMID- 23537548
TI  - Mitochondrial cox sequences of Nilaparvata lugens and Sogatella furcifera
      (Hemiptera, Delphacidae): low specificity among Asian planthopper populations.
AB  - The brown planthoppers (BPH) Nilaparvata lugens (Stal) and the white-backed
      planthoppers (WBPH) Sogatella furcifera (Horvath) annually migrate from tropical
      and subtropical regions to temperate regions in Asia, including Japan, Korea and
      northern China. To elucidate the genetic divergence based on geography of
      planthoppers and to estimate their migration route on the basis of molecular
      data, we analysed a part of their mitochondrial genome sequences. Sequences of
      cytochrome oxidase subunit I (cox1) - transfer RNA for Leu (trnL2) - cox2 were
      determined for 579 BPH (1,928 bp) and 464 WBPH (1,927 bp) individuals collected
      from 31 and 25 locations, respectively, in East and Southeast Asia. Thirty and 20
      mitochondrial haplotypes were detected for BPH and WBPH, respectively. Single
      populations of both planthoppers included multiple haplotypes, and many
      haplotypes were shared in some populations and areas. The most frequently
      detected haplotypes accounted for approximately 50% of all BPH and WBPH
      individuals. To evaluate gene flow among planthoppers in different regions in
      Asia, pairwise fixation index (Fst) values were calculated. For BPH, high Fst
      values (0.580-0.926) were shown between planthoppers in Papua New Guinea (PNG)
      and the other areas and moderate Fst values (0.176-0.362) were observed between
      those in southern Philippines and other areas. For WBPH, the Fst value was the
      highest between Taiwan and southern Vietnam (0.236), and low among the other
      areas. AMOVA indicated no genetic structure among eight areas, excluding southern
      Philippines and PNG, for BPH, and among ten areas for WBPH. These data indicate
      that both planthoppers do not show much differentiation of local populations
      and/or have genetically intermixed Asian populations. These data also indicate
      that it may be difficult to distinguish regional planthopper populations on the
      basis of differences in mitochondrial sequences. 

PMID- 23537549
TI  - Trends in suicidal ideation in England: the national psychiatric morbidity
      surveys of 2000 and 2007.
AB  - BACKGROUND: Recent falls in suicide rates should be accompanied by a decline in
      the prevalence of suicidal ideation. METHOD: We used a pseudo-cohort analytic
      strategy to examine trends in suicidal ideation measured identically in 2000 and
      2007, in nationally representative English probability samples of adults aged >=
      16 years. Suicidal ideation included tiredness of life, death wishes and thoughts
      of suicide. Logistic regression models were fitted to estimate trends in age
      specific prevalence of suicidal ideation in the past year and past week between
      2000 and 2007. RESULTS: There were 6799 participants aged 16-71 years in 2000,
      and 6815 participants aged 16-78 years in 2007. There was little evidence of
      trends in prevalence of suicidal ideation, with the exception of women aged 44-50
      years in 2007, whose prevalence was unusually high. Prevalence of suicidal
      ideation in the past year followed a W-shaped profile with age, with peaks at the
      transition to adulthood, in the forties, and in the oldest participants.
      CONCLUSIONS: Despite falling suicide rates, suicidal ideation did not decline
      overall between 2000 and 2007. This may indicate the success of the National
      Suicide Prevention Strategy. Women aged 44-50 years in 2007 were, however,
      particularly prone to suicidal ideation. As they also have the highest age
      adjusted prevalence of common mental disorders and the highest female suicide
      rate, there are clear implications for treatment access, availability and
      delivery in primary care.

PMID- 23537550
TI  - [Clinical characteristic analysis of 96 cases of hypersensitivity pneumonitis].
AB  - OBJECTIVE: To improve understanding of the clinical characteristics and diagnosis
      of hypersensitivity pneumonitis (HP). METHODS: We retrospectively analyzed the
      clinical data, including clinical symptoms, laboratory tests, exposure, pulmonary
      function tests, chest CT imaging and cytological classification of
      bronchoalveolar lavage (BAL) of 96 patients with HP from Jan 2001 to Jun 2011 in
      Peking Union Medical College Hospital. We divided the patients into 2 groups: a
      pathologically-confirmed group and a clinically-suspected group. RESULTS: There
      were 58 females and 41 males. The median age at the diagnosis was 53 years. The
      most common exposures were low-molecular-weight chemicals (42.7%) and animal
      proteins (37.5%). Common clinical symptoms included dyspnea on exertion (90.6%)
      and cough (76.0%). Pulmonary function test showed diffusion abnormality (73.5%)
      and restrictive ventilatory impairment (59.7%). Chest CT scan revealed patchy or
      diffuse bilateral ground-glass opacities (64.6%), centrilobular nodules (21.9%),
      and air trapping (15.6%). Reticulation (45.8%), traction bronchiectasis (21.9%)
      and honeycombing(9.4%) were present in chronic HP. BAL lymphocyte counts > 0.2
      and CD4/CD8 < 0.9 were more commonly seen in patients with a disease course of
      less than 1 year. The pathologically-confirmed group and the clinically-suspected
      group shared many similar characteristics including age at diagnosis, gender,
      clinical manifestation, pulmonary function impairments and imaging findings, but
      significant differences existed in certain parameters. In the pathologically-
      confirmed group, the duration of disease was longer (24 months vs 6 months, Z = 
      2.492, P = 0.013) and clubbed fingers were more common (23.4% vs 8.2%, chi(2) =
      4.227, P = 0.040). Diffusion abnormality was present in more patients of this
      group (90.7% vs 44.0%, chi(2) = 35.219, P < 0.01). By CT scan, reticulation,
      traction bronchiectasis and honeycombing (57.5% vs 26.5%, chi(2) = 9.434, P <
      0.01) were more evident as compared to the clinically-suspected group. The value
      of transbronchial lung biopsy for diagnosing HP was limited, with a positive
      result of only 8.2%. Surgical lung biopsy was needed in uncertain cases.
      CONCLUSION: The diagnosis of HP was difficult. In some cases a clinical diagnosis
      can be made by combination of history of exposure, CT manifestations and cell
      classification of BAL. For atypical cases a multi-disciplinary approach including
      pathologists, radiologists and pulmonologists is needed.

PMID- 23537551
TI  - [Retrospective analysis of 11 cases of respiratory amyloidosis].
AB  - OBJECTIVE: To investigate the clinical manifestation, diagnosis and treatment of
      respiratory amyloidosis. METHODS: Data of 11 patients with respiratory
      amyloidosis diagnosed by biopsy in Peking University First Hospital from January
      2002 to January 2012 were analyzed, and the related literatures were reviewed.
      RESULTS: In the last decade, 250 of 389 402 hospitalized patients were
      pathologically diagnosed as having amyloidosis, and 11 cases were pathologically
      confirmed to be respiratory amyloidosis. In these 11 patients, 4 cases were with
      serum amyloid A (AA) amyloidosis and 7 with light-chain (AL) amyloidosis. The
      main clinical manifestations included hoarseness, cough and dyspnea. In 4 cases
      with AA type unilateral larynx was involved and there was no recurrence after
      surgical resection. Of 7 cases with AL type, 2 cases had involvement of bilateral
      larynxes and both relapsed after surgery. Diffuse involvement of trachea and
      bronchi was found in 4 cases, and the chest CT scans showed diffuse thickening
      and local calcification of the airway wall, bronchial stenosis and nodules
      protruding into the lumen. Bronchoscopy showed airway mucosal hypertrophy,
      hyperemia, edema and bronchial stenosis. Lung involvement was found in 3 cases, 2
      of which presented with diffuse pulmonary interstitial infiltrates, and another
      case presented with solitary pulmonary mass and extrapulmonary lesions. Of the 7
      cases with AL type, 3 cases were treated by chemotherapy and/or radiotherapy, 3
      received surgery, 2 underwent autologous hematopoietic stem cell transplantation,
      and 2 underwent bronchoscopic interventional therapy. Within 3 years of follow
      up, 4 patients were alive, 2 dead and 1 lost to follow up. CONCLUSIONS:
      Respiratory amyloidosis, which can be divided into AA and AL types, is clinically
      rare. Patients with AA type usually present with local lesions, which can be
      cured by surgery, while patients with AL type often present with diffuse lesions
      and require integrated therapies including surgery, interventional treatment,
      chemotherapy, radiotherapy, and autologous hematopoietic stem cell
      transplantation.

PMID- 23537552
TI  - [The morphological alteration of the diaphragm in patients with chronic
      obstructive pulmonary disease with three-dimensional reconstruction of 64-slice
      spiral CT].
AB  - OBJECTIVE: To study the morphological alteration of the diaphragm with three
      dimensional reconstruction in patients with chronic obstructive pulmonary disease
      (COPD), and to evaluate the relationship between morphological parameters and
      pulmonary function. METHODS: Subjects were consecutively recruited in Shanghai
      East Hospital of Tongji University from July 2010 to April 2011. They were
      divided into a COPD (30 males) group, including mild (n = 10), moderate (n = 10),
      and severe/very severe (n = 10), and a control group (20 males); with the age of
      the subjects ranging from 45 to 80 years old. The subjects were asked to take
      pulmonary function test. Each subject underwent CT scanning in residual volume
      (RV) and total lung capacity (TLC) phases. The imaging of CT scanning was used to
      reconstruct three-dimensional diaphragm with the special computer software. The
      length of total diaphragm (Ldi), including the part of the zone apposition (Lap)
      and part of the dome (Ldo) under coronal (C) and sagittal (S) were observed. The
      surface area of the diaphragm (Adi), surface area (Aap) of the zone of apposition
      and surface area (Ado) of the dome were measured as well. In addition, the
      relationship between morphological indexs and pulmonary function were evaluated.
      RESULTS: In RV phase, compared with the control, Ldi and Lap were significantly
      lower in COPD, S-Ldi: (23.3 +/- 2.9) cm vs (31.1 +/- 4.3) cm (t = 4.12, P <
      0.05); S-Lap: (5.4 +/- 1.9) cm vs (12.7 +/- 2.0) cm, (t = 6.96, P < 0.05); the
      difference was more obvious in sagittal slices as compared to the coronal slices.
      The reduction of S-Ldi was more pronounced in the part of S-Lap. In RV phase, Adi
      and Aap were also significant lower in COPD, Adi: (571 +/- 119) cm(2) vs (811 +/-
      95) cm(2) (t = 4.06, P < 0.05). Aap: (270 +/- 99) cm(2) vs (471 +/- 61) cm(2) (t
      = 4.33, P < 0.05). Aap decreased more significantly, and accounted for the most
      part of reduction of Adi. There was a significant positive correlation between
      Aap and S-Lap with pulmonary function (r = 0.577 - 0.787, all P < 0.05),
      especially for Aap (r = 0.787). In TLC phase, only C-Ldi and C-Lap decreased
      significantly (t = 3.08, t = 2.80 respectively, all P < 0.05). CONCLUSIONS: The
      diaphragmatic length and surface area decreased in patients with COPD, which were
      more pronounced in the part of the zone of apposition and occurred during RV
      phase. The dimension of the zone of apposition could be a parameter to reflect
      the severity of the disease.

PMID- 23537553
TI  - [Methodology research and preliminary assessment of Mycobacterium tuberculosis
      detection by immunomagnetic beads combined with functionalized fluorescent
      quantum dots].
AB  - OBJECTIVE: To establish a detection method for Mycobacterium tuberculosis (MTB)
      by immunomagnetic beads combined with functionalized fluorescent quantum dots
      technology, and to investigate the optimal test condition and the diagnostic
      value of this method. METHODS: MTB standard strain H37Rv was used as detection
      object. Nanobeads and quantum dots were prepared by using wet chemical method,
      and conjugated separately with MTB binding peptide H8 to obtain immunomagnetic
      beads and functionalized fluorescent quantum dots, which could react with H37Rv
      simultaneously and form a ternary complex structure. Based on measurement of the
      fluorescence value and observation under fluorescence microscopy to determine if
      MTB existed in the sample, a new detection method of MTB using nanotechnology was
      established. The optimal detection concentration and reaction time of
      immunomagnetic beads and quantum dots were investigated, and the detection limit
      and specificity of this detection method were evaluated by using bacterial
      suspension and simulation sputum samples. RESULTS: By fluorescence microscopy
      examination, it was found that conjugated immunomagnetic beads and functionalized
      fluorescent quantum dots both bound with H37Rv and formed the ternary complex
      structure. The fluorescent value ratio of the experimental group and the control
      group could be 4:1. The best detection concentration of immunomagnetic beads and
      functionalized fluorescent quantum dots was 100 mg/L and the optimal incubation
      time was 2 h. The detection limit of H37Rv bacterial suspension and simulation
      sputum sample were both 10(3) CFU/ml. The detection results for 3 non
      mycobacteria were all negative, while for the 12 types of NTM, only Mycobacterium
      parafortuitum, Mycobacterium aurum, Mycobacterium smegmatis and Mycobacterium
      fortuitum were positive, and others were all negative. CONCLUSION: The detection
      method of immunomagnetic beads combined with fluorescence quantum dots can be a
      new detection method for MTB, but the clinical value needs to be evaluated
      further.

PMID- 23537547
TI  - EURObservational Research Programme: regional differences and 1-year follow-up
      results of the Heart Failure Pilot Survey (ESC-HF Pilot).
AB  - AIMS: The ESC-HF Pilot survey was aimed to describe clinical epidemiology and 1
      year outcomes of outpatients and inpatients with heart failure (HF). The pilot
      phase was also specifically aimed at validating structure, performance, and
      quality of the data set for continuing the survey into a permanent Registry.
      METHODS: The ESC-HF Pilot study is a prospective, multicentre, observational
      survey conducted in 136 Cardiology Centres in 12 European countries selected to
      represent the different health systems across Europe. All outpatients with HF and
      patients admitted for acute HF on 1 day per week for eight consecutive months
      were included. From October 2009 to May 2010, 5118 patients were included: 1892
      (37%) admitted for acute HF and 3226 (63%) patients with chronic HF. The all
      cause mortality rate at 1 year was 17.4% in acute HF and 7.2% in chronic stable
      HF. One-year hospitalization rates were 43.9% and 31.9%, respectively, in
      hospitalized acute and chronic HF patients. Major regional differences in 1-year
      mortality were observed that could be explained by differences in characteristics
      and treatment of the patients. CONCLUSION: The ESC-HF Pilot survey confirmed that
      acute HF is still associated with a very poor medium-term prognosis, while the
      widespread adoption of evidence-based treatments in patients with chronic HF
      seems to have improved their outcome profile. Differences across countries may be
      due to different local medical practice as well to differences in healthcare
      systems. This pilot study also offered the opportunity to refine the
      organizational structure for a long-term extended European network.

PMID- 23537555
TI  - [B-type natriuretic peptide and weaning from mechanical ventilation].

PMID- 23537554
TI  - [Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae
      isolated from multi-centers across China, 2010 - 2011].
AB  - OBJECTIVE: To investigate the trends of resistance of S. pneumoniae and to
      evaluate the potential coverage of pneumococcal conjugate vaccine. METHODS: The
      antibiotic susceptibility and serotype distribution of 471 pneumococcal strains
      isolated from pneumococcal diseases in 13 hospitals across China during 2010 to
      2011 were studied. In vitro susceptibility to 15 antimicrobial agents was
      determined by agar dilution method. Serotyping of S. pneumoniae was performed by
      using latex and quelling reaction. Vaccine coverage by 7-, 10-, 13- and 23-
      valent conjugate vaccines was estimated by calculating the percentage of isolates
      that belonged to the serotypes included in the vaccines. RESULTS: Among all
      strains tested, 50.1% (236/471) was resistant to penicillin (Oral breakpoint, MIC
      >= 2 mg/L). Overall, 27.4% (129/471), 60.3% (284/471), 58.8% (277/471) and 18.5%
      (87/471) of S. pneumoniae were resistant to amoxicillin/clavulanate, cefaclor,
      cefuroxime and ceftriaxone, respectively.1.5% (7/471) of all stains were
      resistant to levofloxacin and 0.6% (3/471) of all strains were resistant to
      moxifloxacin. The resistance rates to other antibiotic agents, such as
      erythromycin, clindamycin, tetracycline, trimethoprim/sulfamethoxazole, and
      chloramphenicol, were 93.2% (439/471), 88.7% (417/471), 89.6% (422/471), 62.8%
      (296/471) and 22.1% (104/471), respectively. The most prevalent serotype was 19F
      (112, 23.8%), followed by 19A (63, 13.4%), 3 (48, 10.2%), 14 (43, 9.1%), 23F (29,
      6.2%), 15 (25, 5.3%) and 6A (23, 4.9%). The potential coverage by 7- and 13
      valent pneumococcal conjugate vaccines was 45.3% (213/471) and 76% (358/471),
      respectively. The potential coverage of PCV7 and PCV13 in children were 59.0%
      (72/122) and 86.9% (106/122), and the potential coverage of PCV7 and PCV13 in
      adult were 42.3% (94/222) and 73.4% (163/222). CONCLUSIONS: The antibiotic
      resistance of S. pneumoniae was serious in China, especially to tetracycline,
      erythromycin and clindamycin. The majority of serotypes 19A and 19F was
      penicillin-resistant. The potential coverage of PCV7 and PCV13 in children was
      higher than those in adult. PCV13 could cover most of the isolates, especially
      for penicillin-resistant S. pneumoniae.

PMID- 23537556
TI  - [Research progresses of predictors of chronic thromboembolic pulmonary
      hypertension].

PMID- 23537558
TI  - Positron emission tomography/computerised tomography imaging in detecting and
      managing recurrent cervical cancer: systematic review of evidence, elicitation of
      subjective probabilities and economic modelling.
AB  - BACKGROUND: Cancer of the uterine cervix is a common cause of mortality in women.
      After initial treatment women may be symptom free, but the cancer may recur
      within a few years. It is uncertain whether it is more clinically effective to
      survey asymptomatic women for signs of recurrence or to await symptoms or signs
      before using imaging. OBJECTIVES: This project compared the diagnostic accuracy
      of imaging using positron emission tomography/computerised tomography (PET-CT)
      with that of imaging using CT or magnetic resonance imaging (MRI) alone and
      evaluated the cost-effectiveness of adding PET-CT as an adjunct to standard
      practice. DATA SOURCES: Standard systematic review methods were used to obtain
      and evaluate relevant test accuracy and effectiveness studies. Databases searched
      included MEDLINE, EMBASE, Science Citation Index and The Cochrane Library. All
      databases were searched from inception to May 2010. REVIEW METHODS: Study quality
      was assessed using appropriately modified Quality Assessment of Diagnostic
      Accuracy Studies (QUADAS) criteria. Included were any studies of PET-CT, MRI or
      CT compared with the reference standard of histopathological findings or clinical
      follow-up in symptomatic women suspected of having recurrent or persistent
      cervical cancer and in asymptomatic women a minimum of 3 months after completion
      of primary treatment. Subjective elicitation of expert opinion was used to
      supplement diagnostic information needed for the economic evaluation. The
      effectiveness of treatment with chemotherapy, radiotherapy, chemoradiotherapy,
      radical hysterectomy and pelvic exenteration was systematically reviewed. Meta
      analysis was carried out in RevMan 5.1 (The Cochrane Collaboration, The Nordic
      Cochrane Centre, Copenhagen, Denmark) and Stata version 11 (StataCorp LP, College
      Station, Texas, USA). A Markov model was developed to compare the relative cost
      effectiveness using TreeAge Pro software version 2011 (TreeAge Software Inc.,
      Evanston, IL, USA). RESULTS: For the diagnostic review, a total of 7524 citations
      were identified, of which 12 test accuracy studies were included in the review:
      six studies evaluated PET-CT, two evaluated MRI, three evaluated CT and one
      evaluated both MRI and CT. All studies were small and the majority evaluated
      imaging in women in whom recurrence was suspected on the basis of symptoms. The
      PET-CT studies evaluated local and distant recurrence and most used methods
      similar to current practice, whereas five of the six CT and MRI studies evaluated
      local recurrence only and not all employed currently used methods. Meta-analysis
      of PET-CT studies gave a sensitivity of 92.2% [95% confidence interval (CI) 85.1%
      to 96.0%] and a specificity of 88.1% (95% CI 77.9% to 93.9%). MRI sensitivities
      and specificities varied between 82% and 100% and between 78% and 100%,
      respectively, and CT sensitivities and specificities varied between 78% and 93%
      and between 0% and 95%, respectively. One small study directly compared PET-CT
      with older imaging methods and showed more true-positives and fewer false
      negatives with PET-CT. The subjective elicitation from 21 clinical experts gave
      test accuracy results for asymptomatic and symptomatic women and the results for
      symptomatic women were similar to those from the published literature. Their
      combined opinions also suggested that the mean elicited increase in accuracy from
      the addition of PET-CT to MRI and/or CT was less than the elicited minimum
      important difference in accuracy required to justify the routine addition of PET
      CT for the investigation of women after completion of primary treatment. For the
      effectiveness review, a total of 24,943 citations were identified, of which 62
      studies were included (chemotherapy, 19 randomised controlled trials;
      radiotherapy or chemoradiotherapy, 16 case series; radical hysterectomy and
      pelvic exenteration, 27 case series). None provided the effectiveness of
      cisplatin monotherapy, the most commonly used chemotherapeutic agent in the NHS,
      compared with supportive care in a background of other treatment such as
      radiotherapy in recurrent and persistent cervical cancer. The model results
      showed that adding PET-CT to the current treatment strategy of clinical
      examination, MRI and/or CT scan was significantly more costly with only a minimal
      increase in effectiveness, with incremental cost-effectiveness ratios for all
      models being > L1M per quality-adjusted life-year (QALY) and the additional cost
      per additional case of recurrence being in the region of L600,000. LIMITATIONS:
      There was considerable uncertainty in many of the parameters used because of a
      lack of good-quality evidence in recurrent or persistent cervical cancer. The
      evidence on diagnostic and therapeutic impact incorporated in the economic model
      was poor and there was little information on surveillance of asymptomatic women.
      CONCLUSIONS: Given the current evidence available, the addition of PET-CT to
      standard practice was not found to be cost-effective in the diagnosis of
      recurrent or persistent cervical cancer. However, although probabilistic
      sensitivity analysis showed that the main conclusion about cost-ineffectiveness
      of PET-CT was firm given the range of assumptions made, should more reliable
      information become available on accuracy, therapeutic impact and effectiveness,
      and the cost of PET-CT reduce, this conclusion may need revision. Current
      guidelines recommending imaging for diagnosis using expensive methods such as PET
      CT need to be reconsidered in the light of the above. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 23537559
TI  - The influence of semantic processing on odor identification ability in
      schizophrenia.
AB  - Despite the well-documented observation of odor identification deficits in
      schizophrenia, less is known about where the disruption in the process of
      correctly identifying an odor occurs. This study aimed to determine the potential
      moderating effects of semantic processing on the observed olfactory dysfunction
      in schizophrenia. Schizophrenia patients and healthy comparison subjects
      completed two versions of the University of Pennsylvania Smell Identification
      Test (UPSIT): an uncued free-response version and the standard multiple-choice
      paradigm, as well as three semantic measures: The Boston Naming Test, Animal
      Naming, and Pyramids and Palm Tree Test. Schizophrenia patients yielded
      significantly lower scores than the comparison group on the standard UPSIT and on
      semantic measures. No relationship was observed between olfactory and semantic
      task performance in patients. These data suggest that odor identification
      deficits may not be primarily due to semantic processing deficits in
      schizophrenia.

PMID- 23537560
TI  - Illness and injury in athletes during the competition period at the London 2012
      Paralympic Games: development and implementation of a web-based surveillance
      system (WEB-IISS) for team medical staff.
AB  - BACKGROUND: In this study we describe (1) the implementation of a novel web-based
      injury and illness surveillance system (WEB-IISS) for use by a team of physicians
      at multisport events and (2) the incidence and characteristics of injuries and
      illness in athletes during the London 2012 Paralympic Games. METHODS: Overall,
      3565 athletes from 160 of the 164 participating countries were followed daily
      over a 14-day period, consisting of a precompetition period (3 days), and a
      competition period (11 days) (49 910 athlete-days). Daily injury and illness data
      were obtained from teams with their own medical support (78 teams, 3329 athletes)
      via the WEB-IISS, and without their own medical support through the London
      Organising Committee of the Olympic Games and Paralympic Games database (82 teams
      and 236 athletes). RESULTS: There were no differences between incidence rates
      (IR) of injury and illness, or between the precompetition and competition
      periods. The IR of injury during the competition period was 12.1/1000 athlete
      days, with an incidence proportion (IP) of 11.6% (95% CI 11.0% to 13.3%). Upper
      limb injuries (35%), particularly of the shoulder (17%) were most common. The IR
      of illness during the competition period was 12.8/1000 athlete-days (95% CI 12.18
      to 1421), with an IP of 10.2%. The IP was highest in the respiratory system
      (27.4%), skin (18.3%) and the gastrointestinal (14.5%) systems. CONCLUSIONS:
      During the competition period, the IR and IP of illness and injury at the Games
      were similar and comparable to the observed rates in other elite competitions. In
      Paralympic athletes, the IP of upper limb injuries is higher than that of lower
      limb injuries and non-respiratory illnesses are more common.

PMID- 23537561
TI  - Effects of early intraoral acesulfame-K stimulation to mice on the adult's sweet
      preference and the expression of alpha-gustducin in fungiform papilla.
AB  - Exposure to artificial sweetener acesulfame-K (AK) at early development stages
      may influence the adult sweet preference and the periphery gustatory system. We
      observed that the intraoral AK stimulation to mice from postnatal day 4 (P4) to
      weaning decreased the preference thresholds for AK and sucrose solutions in
      adulthood, with the preference pattern unchanged. The preference scores were
      increased in the exposure group significantly when compared with the control
      group at a range of concentrations for AK or sucrose solution. Meanwhile, more
      alpha-Gustducin-labeled fungiform taste buds and cells in a single taste bud were
      induced from week 7 by the early intraoral AK stimulation. However, the growth in
      the number of alpha-Gustducin-positive taste bud or positive cell number per
      taste bud occurred only in the anterior region, the rostral 1-mm part, but not in
      the intermediate region, the caudal 4-mm part, of the anterior two-third of the
      tongue containing fungiform papillae. This work extends our previous observations
      and provides new information about the developmental and regional expression
      pattern of alpha-Gustducin in mouse fungiform taste bud under early AK-stimulated
      conditions.

PMID- 23537562
TI  - Transmission of Mycobacterium tuberculosis from an Asian elephant (Elephas
      maximus) to a chimpanzee (Pan troglodytes) and humans in an Australian zoo.
AB  - Mycobacterium tuberculosis is primarily a pathogen of humans. Infections have
      been reported in animal species and it is emerging as a significant disease of
      elephants in the care of humans. With the close association between humans and
      animals, transmission can occur. In November 2010, a clinically healthy Asian
      elephant in an Australian zoo was found to be shedding M. tuberculosis; in
      September 2011, a sick chimpanzee at the same zoo was diagnosed with tuberculosis
      caused by an indistinguishable strain of M. tuberculosis. Investigations included
      staff and animal screening. Four staff had tuberculin skin test conversions
      associated with spending at least 10 hours within the elephant enclosure; none
      had disease. Six chimpanzees had suspected infection. A pathway of transmission
      between the animals could not be confirmed. Tuberculosis in an elephant can be
      transmissible to people in close contact and to other animals more remotely. The
      mechanism for transmission from elephants requires further investigation.

PMID- 23537563
TI  - Is global health really global?

PMID- 23537564
TI  - Molecularly imprinted solid-phase extraction in the analysis of agrochemicals.
AB  - The molecular imprinting technique is a highly predeterminative recognition
      technology. Molecularly imprinted polymers (MIPs) can be applied to the cleanup
      and preconcentration of analytes as the selective adsorbent of solid-phase
      extraction (SPE). In recent years, a new type of SPE has formed, molecularly
      imprinted polymer solid-phase extraction (MISPE), and has been widely applied to
      the extraction of agrochemicals. In this review, the mechanism of the molecular
      imprinting technique and the methodology of MIP preparations are explained. The
      extraction modes of MISPE, including offline and online, are discussed, and the
      applications of MISPE in the analysis of agrochemicals such as herbicides,
      fungicides and insecticides are summarized. It is concluded that MISPE is a
      powerful tool to selectively isolate agrochemicals from real samples with higher
      extraction and cleanup efficiency than commercial SPE and that it has great
      potential for broad applications. 

PMID- 23537565
TI  - Normal mode analysis based on an elastic network model for biomolecules in the
      Protein Data Bank, which uses dihedral angles as independent variables.
AB  - We have developed a computer program, named PDBETA, that performs normal mode
      analysis (NMA) based on an elastic network model that uses dihedral angles as
      independent variables. Taking advantage of the relatively small number of degrees
      of freedom required to describe a molecular structure in dihedral angle space and
      a simple potential-energy function independent of atom types, we aimed to develop
      a program applicable to a full-atom system of any molecule in the Protein Data
      Bank (PDB). The algorithm for NMA used in PDBETA is the same as the computer
      program FEDER/2, developed previously. Therefore, the main challenge in
      developing PDBETA was to find a method that can automatically convert PDB data
      into molecular structure information in dihedral angle space. Here, we illustrate
      the performance of PDBETA with a protein-DNA complex, a protein-tRNA complex, and
      some non-protein small molecules, and show that the atomic fluctuations
      calculated by PDBETA reproduce the temperature factor data of these molecules in
      the PDB. A comparison was also made with elastic-network-model based NMA in a
      Cartesian-coordinate system.

PMID- 23537566
TI  - Extending the applicability of the O-ring theory to protein-DNA complexes.
AB  - Many biological processes depend on protein-based interactions, which are
      governed by central regions with higher binding affinities, the hot-spots. The O
      ring theory or the "Water Exclusion" hypothesis states that the more deeply
      buried central regions are surrounded by areas, the null-spots, whose role would
      be to shelter the hot-spots from the bulk solvent. Although this theory is well
      established for protein-protein interfaces, its applicability to other protein
      interfaces remains unclear. Our goal was to verify its applicability to protein
      DNA interfaces. We performed Molecular Dynamics simulations in explicit solvent
      of several protein-DNA complexes and measured a variety of solvent accessible
      surface area (SASA) features, as well as, radial distribution functions of hot
      spots and null-spots. Our aim was to test the influence of water in their
      coordination sphere. Our results show that hot-spots tend to have fewer water
      molecules in their neighborhood when compared to null-spots, and higher values of
      DeltaSASA, which confirms their occlusion from solvent. This study provides
      evidence in support of the O-ring theory with its applicability to a new type of
      protein-based interface: protein-DNA.

PMID- 23537568
TI  - Phase transformation and subsurface damage in 3Y-TZP after sandblasting.
AB  - OBJECTIVE: The goal of this work is to investigate t-m phase transformation, and
      subsurface damage in 3Y-TZP after sandblasting. METHODS: Commercial grade 3Y-TZP
      powder was conventionally sintered and fully dense specimens were obtained.
      Specimens were sandblasted using different particle sizes (110 and 250MUm) and
      pressures (2 and 4bar) for 10s. Phase transformation was measured on the surface
      and in the cross-section using X-ray diffraction and micro Raman spectroscopy,
      respectively. Subsurface damage was investigated on cross-sections using SEM and
      in shallow cross-sections machined by focused ion beam. RESULTS: Sandblasting
      induced monoclinic volume fraction is in the range of 12-15% on the surface. In
      the cross-section, a non-homogeneous phase transformation gradient is found up to
      the depth of 12+/-1MUm. The subsurface damage observed was plastic deformation in
      grains with the presence of martensite plates, and this effect is found to be
      larger in specimens sandblasted with large particles. SIGNIFICANCE: The extent of
      subsurface tetragonal-monoclinic transformation and damage induced by
      sandblasting are reported for different sandblasting conditions. This knowledge
      is critical in order to understand the effect of sandblasting on mechanical
      properties of zirconia used to fabricate dental crowns and frameworks.

PMID- 23537567
TI  - Insurance status and outcome after intracerebral hemorrhage: findings from Get
      With The Guidelines-stroke.
AB  - BACKGROUND: [corrected] Few studies have examined associations among insurance
      status, treatment, and outcomes in patients hospitalized for intracerebral
      hemorrhage (ICH). METHODS: Through retrospective analyses of the Get With The
      Guidelines (GWTG)-Stroke database, a national prospective stroke registry, from
      April 2003 to April 2011, we identified 95,986 nontransferred subjects
      hospitalized with ICH. Insurance status was categorized as Private/Other,
      Medicaid, Medicare, or None/Not Documented (ND). Associations between insurance
      status and in-hospital outcomes and quality of care measures were analyzed using
      patient- and hospital-specific variables as covariates. RESULTS: There were
      significant differences in age and frequency of comorbid conditions by insurance
      group. Compliance with evidence-based quality of care indicators varied across
      all insurance status groups (P < .0001) but was generally high. In adjusted
      analysis with the Private insurance group as reference, the None/ND group most
      consistently demonstrated higher odds ratios (ORs) for quality of care measures
      (Dysphagia Screen: OR 1.10, 95% confidence interval [CI] 1.02-1.17, P = .0096;
      Stroke Education: OR 1.16, 95% CI 1.05-1.29, P = .0042; and Rehabilitation: OR
      1.25, 95% CI 1.08-1.44, P = .0027). In-hospital mortality rates were higher for
      None/ND, Medicaid, and Medicare patients; after risk adjustment, the None/ND
      group had the highest mortality risk (OR 1.29, 95% CI 1.21-1.38, P < .0001).
      Medicare and Medicaid patients had lower adjusted odds for both independent
      ambulation at discharge and discharge to home when compared with the
      Private/Other group. CONCLUSIONS: GWTG-Stroke ICH patients demonstrated
      differences in mortality, functional status, discharge destination, and quality
      of care measures associated with insurance status.

PMID- 23537569
TI  - Investigation of the hydration and bioactivity of radiopacified tricalcium
      silicate cement, Biodentine and MTA Angelus.
AB  - OBJECTIVE: Novel root-end filling materials are composed of tricalcium silicate
      (TCS) and radiopacifier as opposed to the traditional mineral trioxide aggregate
      (MTA) which is made up of clinker derived from Portland cement and bismuth oxide.
      The aim of this research was to characterize and investigate the hydration of a
      tricalcium silicate-based proprietary brand cement (BiodentineTM) and a
      laboratory manufactured cement made with a mixture of tricalcium silicate and
      zirconium oxide (TCS-20-Z) and compare their properties to MTA AngelusTM.
      METHODS: The materials investigated included a cement containing 80% of TCS and
      20% zirconium oxide (TCS-20-Z), BiodentineTM and MTA AngelusTM. The specific
      surface area and the particle size distribution of the un-hydrated cements and
      zirconium oxide were investigated using a gas adsorption method and scanning
      electron microscopy. Un-hydrated cements and set materials were tested for
      mineralogy and microstructure, assessment of bioactivity and hydration. Scanning
      electron microscopy, X-ray energy dispersive analysis, X-ray fluorescence
      spectroscopy, X-ray diffraction, Rietveld refined X-ray diffraction and
      calorimetry were employed. The radiopacity of the materials was investigated
      using ISO 6876 methods. RESULTS: The un-hydrated cements were composed of
      tricalcium silicate and a radiopacifier phase; zirconium oxide for both
      BiodentineTM and TCS-20-Z whereas bismuth oxide for MTA AngelusTM. In addition
      BiodentineTM contained calcium carbonate particles and MTA AngelusTM exhibited
      the presence of dicalcium silicate, tricalcium aluminate, calcium, aluminum and
      silicon oxides. TCS and MTA AngelusTM exhibited similar specific surface area
      while BiodentineTM had a greater specific surface area. The cements hydrated and
      produced some hydrates located either as reaction rim around the tricalcium
      silicate grain or in between the grains at the expense of volume containing the
      water initially present in the mixture. The rate of reaction of tricalcium
      calcium silicate was higher for BiodentineTM than for TCS-20-Z owing to its
      optimized particle size distribution, the presence of CaCO3 and the use of CaCl2.
      Tricalcium calcium silicate in MTA hydrated even more slowly than TCS-20-Z as
      evident from the size of reaction rim representative of calcium silicate hydrate
      (C-S-H) around tricalcium silicate grains and the calorimetry measurements. On
      the other hand, calcium oxide contained in MTA AngelusTM hydrated very fast
      inducing an intense exothermic reaction. Calcium hydroxide was produced as a by
      product of reaction in all hydrated cements but in greater quantities in MTA due
      to the hydration of calcium oxide. This lead to less dense microstructure than
      the one observed for both BiodentineTM and TCS-20-Z. All the materials were
      bioactive and allowed the deposition of hydroxyapatite on the cement surface in
      the presence of simulated body fluid and the radiopacity was greater than 3mm
      aluminum thickness. SIGNIFICANCE: All the cement pastes tested were composed
      mainly of tricalcium silicate and a radiopacifier. The laboratory manufactured
      cement contained no other additives. BiodentineTM included calcium carbonate
      which together with the additives in the mixing liquid resulted in a material
      with enhanced chemical properties relative to TCS-20-Z prototype cement. On the
      other hand MTA AngelusTM displayed the presence of calcium, aluminum and silicon
      oxides in the un-hydrated powder. These phases are normally associated with the
      raw materials indicating that the clinker of MTA AngelusTM is incompletely
      sintered leading to a potential important variability in its mineralogy depending
      on the sintering conditions. As a consequence, the amount of tricalcium silicate
      is less than in the two other cements leading to a slower reaction rate and more
      porous microstructure.

PMID- 23537570
TI  - A new modified laser pretreatment for porcelain zirconia bonding.
AB  - OBJECTIVES: The aim of this study was to compare the effects of three different
      surface treatments in enhancing porcelain zirconia bonding. METHODS: Totally, 160
      densely sintered zirconia specimens were prepared and randomly divided into four
      study groups: control (no treatment, Group C), sandblasting (Group S),
      sandblasting followed by regeneration firing (Group SH), and laser irradiation
      (pulse mode) on a CO2 laser system (Group L). After surface treatment, porcelain
      powders were veneered on zirconia surface. Half of the specimens in each group
      were evaluated without aging (initial shear bond strength - initial SBS), and the
      other half was tested after being stored in water for one month (aging SBS). X
      ray diffractometry (XRD) was used to observe any crystallographic transformation
      at zirconia surface. Results were statistically analyzed using analysis of
      variance (ANOVA) and Turkey test (=0.05). RESULTS: The initial average SBS values
      of Group S, Group SH, and Group L were 31.3 +/- 5.7 MPa, 29.2 +/- 7.0 MPa and
      32.1 +/- 7.5 MPa, respectively. The differences among these three groups were not
      significant. The control group had significantly lower value, 24.8 +/- 6.7 MPa,
      than those of Group S and Group L. Furthermore, there was no significant
      difference between initial and aging values in each group. XRD analysis showed
      that sandblasting caused tetragonal to monoclinic phase transformation.
      Regeneration firing reversed such a transformation. However, crystallographic
      transformation could not be detected in laser treated specimens. SIGNIFICANCE:
      Both sandblasting and laser irradiation increased porcelain zirconia bond
      strength. The presented new modified laser pre-treatment might be an alternative
      way to sandblasting for improving zirconia/porcelain integration.

PMID- 23537571
TI  - Shrinkage stress compensation in composite-restored teeth: relaxation or
      hygroscopic expansion?
AB  - OBJECTIVES: Polymerization of composite restorations causes shrinkage, which
      deforms and thus stresses restored teeth. This shrinkage deformation, however,
      has been shown to decrease over time. The objective was to investigate whether
      this reduction was caused by hygroscopic expansion or stress relaxation of the
      composite/tooth complex. METHODS: Extracted molars were mounted in rigid
      stainless steel rings with four spherical reference areas. Twelve molars were
      prepared with large mesioocclusodistal slots, etched, bonded, and restored with a
      composite material (Filtek Supreme, 3M ESPE) in two horizontal layers. Ten intact
      molars were the controls. The teeth were stored either in deionized water or
      silicone oil. They were scanned after preparation (baseline), restoration (0
      week), and after 1, 2, and 4 weeks storage. Scanned tooth surfaces were aligned
      with the baseline using the unchanged reference areas. Cuspal flexure was
      calculated from lingual and buccal surface deformation. To verify that the
      restorations had remained bonded, dye penetration at the interfaces was assessed
      using basic fuchsin dye. Statistical assessment was done by ANOVA followed by
      Student-Newman-Keuls post hoc test (p=0.05). RESULTS: Substantial cuspal
      contraction was found for restored teeth after the composite was cured (13-14 MUm
      cuspal flexure). After 4 weeks cuspal contraction decreased significantly for
      restored teeth stored in water (7.3 +/- 3.2) but not for those stored in silicone
      oil (11.4 +/- 5.0). Dye penetration of the occlusal interface was minimal in both
      groups (106 +/- 87 and 21 +/- 28 MUm in water and silicone oil, respectively).
      SIGNIFICANCE: The results suggest that hygroscopic expansion was the main
      mechanism for shrinkage stress compensation.

PMID- 23537572
TI  - Benzodiazepine and dementia: a time for reflection.

PMID- 23537573
TI  - Long-term temporal trends and estimated transmission rates for Mycobacterium
      bovis infection in an undisturbed high-density badger (Meles meles) population.
AB  - We describe epidemiological trends in Mycobacterium bovis infection in an
      undisturbed wild badger (Meles meles) population. Data were derived from the
      capture, clinical sampling and serological testing of 1803 badgers over 9945
      capture events spanning 24 years. Incidence and prevalence increased over time,
      exhibiting no simple relationship with host density. Potential explanations are
      presented for a marked increase in the frequency of positive serological test
      results. Transmission rates (R0) estimated from empirical data were consistent
      with modelled estimates and robust to changes in test sensitivity and the spatial
      extent of the population at risk. The risk of a positive culture or serological
      test result increased with badger age, and varied seasonally. Evidence consistent
      with progressive disease was found in cubs. This study demonstrates the value of
      long-term data and the repeated application of imperfect diagnostic tests as
      indices of infection to reveal epidemiological trends in M. bovis infection in
      badgers.

PMID- 23537574
TI  - Amino acids as co-amorphous stabilizers for poorly water soluble drugs--Part 1:
      preparation, stability and dissolution enhancement.
AB  - Poor aqueous solubility of an active pharmaceutical ingredient (API) is one of
      the most pressing problems in pharmaceutical research and development because up
      to 90% of new API candidates under development are poorly water soluble. These
      drugs usually have a low and variable oral bioavailability, and therefore an
      unsatisfactory therapeutic effect. One of the most promising approaches to
      increase dissolution rate and solubility of these drugs is the conversion of a
      crystalline form of the drug into its respective amorphous form, usually by
      incorporation into hydrophilic polymers, forming glass solutions. However, this
      strategy only led to a small number of marketed products usually because of
      inadequate physical stability of the drug (crystallization). In this study, we
      investigated a fundamentally different approach to stabilize the amorphous form
      of drugs, namely the use of amino acids as small molecular weight excipients that
      form specific molecular interactions with the drug resulting in co-amorphous
      forms. The two poorly water soluble drugs carbamazepine and indomethacin were
      combined with amino acids from the binding sites of the biological receptors of
      these drugs. Mixtures of drug and the amino acids arginine, phenylalanine,
      tryptophan and tyrosine were prepared by vibrational ball milling. Solid-state
      characterization with X-ray powder diffraction (XRPD) and differential scanning
      calorimetry (DSC) revealed that the various blends could be prepared as
      homogeneous, single phase co-amorphous formulations indicated by the appearance
      of an amorphous halo in the XRPD diffractograms and a single glass transition
      temperature (Tg) in the DSC measurements. In addition, the Tgs of the co
      amorphous mixtures were significantly increased over those of the individual
      drugs. The drugs remained chemically stable during the milling process and the co
      amorphous formulations were generally physically stable over at least 6 months at
      40  degrees C under dry conditions. The dissolution rate of all co-amorphous drug
      amino acid mixtures was significantly increased over that of the respective
      crystalline and amorphous pure drugs. Amino acids thus appear as promising
      excipients to solve challenges connected with the stability and dissolution of
      amorphous drugs.

PMID- 23537575
TI  - Design of pH responsive clickable prodrugs applied to histone deacetylase
      inhibitors: a new strategy for anticancer therapy.
AB  - The aim of this study was to develop clickable prodrugs bearing a tunable pH
      responsive linker designed for acidic pH-mediated release of histone deacetylase
      inhibitors. HDACi are an important class of molecules belonging to the epigenetic
      modulators used for innovative cancer strategies. The behavior of these prodrugs
      was determined by a bioluminescence resonance energy transfer assay in living
      tumor cells. This work demonstrated that this innovative type of clickable
      prodrugs entered cancer cells and showed restored anti proliferative properties
      attributed to the effective release of the HDAC inhibitors. A correlation between
      kinetic studies, dose responses, and biological activities was obtained, making
      such clickable prodrugs good candidates for new strategies in epigenetic-oriented
      anticancer therapies. 

PMID- 23537576
TI  - Congenital portosystemic shunts associated with liver tumours.
AB  - AIM: To evaluate the diagnosis and presentation of liver tumours in patients with
      congenital portosystemic shunts (CPS). MATERIALS AND METHODS: Eight patients were
      diagnosed in Hopital Beaujon as having CPS. All patients underwent Doppler
      ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and
      histological examination of liver tumours. CPS were classified according to
      anatomy and the amount of portal flow deviated to the systemic circulation as:
      total, subtotal, or partial. Liver tumours were diagnosed by needle core biopsy
      (n = 5) or surgery (n = 3). Clinical follow-up was available in all patients but
      one (mean follow-up 36 months; range 1-5 years). RESULTS: Six patients had total
      CPS, one patient had a subtotal CPS, and the last had a partial CPS. All patients
      presented with multiple liver nodules (range four to >15). The tumours were
      characterized as focal nodular hyperplasia (FNH; n = 4), FNH with hepatocellular
      adenoma (n = 2), and regenerative nodular hyperplasia (n = 2). In four of seven
      patients (57%) that had follow-up, tumours showed enlargement or new lesions
      appeared. CONCLUSION: In this series of CPS patients, tumours were all benign,
      multiple, and of hepatocellular origin, and different tumours were present
      simultaneously in two patients. Tumour enlargement or new nodules were common
      during follow-up.

PMID- 23537577
TI  - Evaluation of a dedicated MDCT protocol using iterative image reconstruction
      after cervical spine trauma.
AB  - AIM: To evaluate radiation exposure for 64-row computed tomography (CT) of the
      cervical spine comparing two optimized protocols using filtered back projection
      (FBP) and adaptive statistical iterative reconstruction (ASIR), respectively.
      MATERIALS AND METHODS: Sixty-seven studies using FBP (scanner 1) were
      retrospectively compared with 80 studies using ASIR (scanner 2). The key scanning
      parameters were identical (120 kV dose modulation, 64 * 0.625 mm collimation,
      pitch 0.531:1). In protocol 2, the noise index (NI) was increased from 5 to 25,
      and ASIR and the high-definition (HD) mode were used. The scan length, CT dose
      index (CTDI), and dose-length product (DLP) were recorded. The image quality was
      analysed subjectively by using a three-point scale (0; 1; 2), and objectively by
      using a region of interest (ROI) analysis. Mann-Whitney U and Wilcoxon's test
      were used. RESULTS: In the FBP group, the mean CTDI was 21.43 mGy, mean scan
      length 186.3 mm, and mean DLP 441.15 mGy cm. In the ASIR group, the mean CTDI was
      9.57 mGy, mean scan length 195.21 mm, and mean DLP 204.23 mGy cm. The differences
      were significant for CTDI and DLP (p < 0.001) and scan length (p = 0.01). There
      was no significant difference in the subjective image quality (p > 0.05). The
      estimated mean effective dose decreased from 2.38 mSv (FBP) to 1.10 mSv (ASIR).
      CONCLUSION: The radiation dose of 64-row MDCT can be reduced to a level
      comparable to plain radiography without loss of subjective image quality by
      implementation of ASIR in a dedicated cervical spine trauma protocol. These
      results might contribute to an improved relative risk-to-benefit ratio and
      support the justification of CT as a first-line imaging tool to evaluate cervical
      spine trauma.

PMID- 23537578
TI  - T2 mapping of the articular cartilage in the ankle: correlation to the status of
      anterior talofibular ligament.
AB  - AIM: To evaluate differences in T2 relaxation time of ankle cartilage using
      magnetic resonance imaging (MRI) according to the status of the anterior
      talofibular ligament (ATFL). MATERIALS AND METHODS: The talar trochlear cartilage
      (TTC) was evaluated in 52 patients with ankle pain that were categorized
      according to the status of ATFL; normal (NL; n = 23, mean age 40 years); partial
      tear (PT; n = 21, mean age 39 years); or complete tear (CT; n = 8, mean age 33
      years). The TTC was divided into six compartments (medial anterior, medial
      centre, medial posterior, lateral anterior, lateral centre, and lateral
      posterior). The mean T2 value of each compartment was obtained using the multi
      echo sequence. Data were analysed with parametric and non-parametric statistical
      tests. RESULTS: The mean T2 values of the TTC showed significant differences
      between the three groups; NL, PT, and CT (p < 0.001). The T2 value between the
      three ligamentous groups were significantly different in the medial anterior,
      lateral anterior, and lateral centre compartments (p = 0.003, 0.002, 0.002,
      respectively). T2 values of the PT and CT groups were significantly higher than
      those of the NL group in the medial anterior compartment (p = 0.015, 0.002) and
      lateral anterior compartment (p = 0.026, <0.001). The T2 value of the CT group
      was significantly higher than that of NL and PT groups in the lateral centre
      compartment (p < 0.001, 0.031). CONCLUSION: The T2 value of the TTC in patients
      with ATFL injury increased at the medial anterior, lateral anterior, and lateral
      centre compartments.

PMID- 23537579
TI  - The role of colour Doppler sonography in the diagnosis of lower limb Klippel
      Trenaunay syndrome.
AB  - AIM: To investigate the accuracy of colour Doppler sonography as compared to
      phlebography in patients with Klippel-Trenaunay syndrome (KTS). MATERIALS AND
      METHODS: From September 2004 to May 2012, 59 consecutive patients seen in
      Shandong medical imaging research institute with a clinical suggestion of KTS
      were included. Thirty-four were female and 25 were male, with a mean age of 28.4
      years. Colour Doppler sonography was used to assess the lower limb veins. The
      main sonographic criteria for a positive diagnosis were visualization of the
      lateral vein or sciatic vein, capillary haemangioma, and abnormality of the deep
      veins. These data were compared with phlebography findings. The kappa statistic
      was used to determine the level of agreement. The sensitivity, specificity,
      positive and negative predictive values, and accuracy of colour Doppler
      sonography as a diagnostic test were assessed. RESULTS: Colour Doppler sonography
      findings were positive in 21 of 59 patients with a clinical suggestion of KTS.
      The diagnosis was confirmed using phlebography in 22 patients. There were two
      false-positive results and one false-negative result by colour Doppler
      sonography. The kappa-value was 0.892. Sensitivity, specificity, positive and
      negative predictive values, and accuracy for colour Doppler sonography were 95.4,
      94.6, 91.3, 97.2, and 94.9%, respectively. CONCLUSION: Colour Doppler sonography
      is an accurate, reliable, and non-invasive investigation in the assessment of
      patients with suspected KTS.

PMID- 23537580
TI  - Linezolid versus vancomycin for meticillin-resistant Staphylococcus aureus
      infection: a meta-analysis of randomised controlled trials.
AB  - Linezolid is the first available oxazolidinone, possessing broad-spectrum
      activity against Gram-positive bacteria and a favourable pharmacokinetic profile.
      The aim of this study was to compare the efficacy and safety of linezolid with
      vancomycin, the gold-standard treatment, for meticillin-resistant Staphylococcus
      aureus (MRSA)-related infections. A meta-analysis of randomised controlled trials
      (RCTs) identified in PubMed, the Cochrane Library and Embase was performed. Nine
      RCTs, involving 5249 patients, were included in the meta-analysis. The results
      indicated that linezolid was associated with superior efficacy compared with
      vancomycin for MRSA-related infection in terms of clinical treatment success [8
      RCTs, 2174 patients, odds ratio (OR) = 1.77, 95% confidence interval (CI) 1.22
      2.56] and microbiological treatment success (9 RCTs, 1555 patients, OR = 1.78,
      95% CI 1.22-2.58). Although no difference was found regarding the overall
      incidence of drug-related adverse events (AEs) and serious AEs (SAEs) between the
      linezolid and vancomycin therapy groups (drug-related AEs, 8 RCTs, 5034 patients,
      OR = 1.20, 95% CI 0.98-1.48; SAEs, 5 RCTs, 2072 patients, OR = 1.00, 95% CI 0.74
      1.36), the linezolid therapy group was associated with significantly fewer
      patients experiencing abnormal renal function (reduced by ca. 60% compared with
      the vancomycin therapy group; 4 RCTs, 2531 patients, OR = 0.39, 95% CI 0.28
      0.55), which is a well-recognised limitation of vancomycin. This meta-analysis
      provides evidence that linezolid possesses significant advantages compared with
      vancomycin and may be a superior alternative for MRSA-related infection.

PMID- 23537581
TI  - All-cause mortality imbalance in the tigecycline phase 3 and 4 clinical trials.
AB  - In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was
      higher in the tigecycline group versus the comparator group. Study-level
      mortality risk differences were pooled using a random-effects meta-analysis.
      Statistical models evaluated the association between patient-level all-cause
      mortality and baseline factors using logistic regression, recursive partitioning
      [classification and regression tree (CART) analysis] and survival techniques. The
      estimated risk difference (tigecycline minus comparator) in all-cause mortality
      from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical
      modelling identified baseline bacteraemia associated with mortality only in the
      tigecycline group. In patients with ventilator-associated pneumonia (VAP) and
      baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7%
      (1/13) for the comparator group. Study-level and patient-level analyses have
      identified that patients in the hospital-acquired pneumonia trial, particularly
      those with VAP with baseline bacteraemia, were at a higher risk of clinical
      failure and mortality.

PMID- 23537582
TI  - Integrated chemical and biological analysis to explain estrogenic potency in bile
      extracts of red mullet (Mullus barbatus).
AB  - A biological screening was performed to establish the total exposure to
      estrogenic compounds of red mullet (Mullus barbatus) collected at several sites
      along the Spanish Mediterranean coast by testing male fish bile extracts using
      the in vitro ER-LUC reporter gene assay. In addition, major metabolites were
      identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1
      pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4
      tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas
      chromatography-mass spectrometry in electron ionization mode (GC-EI-MS). Relative
      in vitro estrogenic potencies of the chemically quantified compounds were also
      tested. The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP
      were found in fish from Barcelona and from the Mar Menor coastal lagoon. However,
      these concentrations can be considered relatively low compared to values reported
      in red mullet from other polluted waters in the Mediterranean Sea. The
      contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency
      measured in male fish bile was found to be negligible, indicating the presence of
      other estrogenic compounds in red mullet bile. Estrogenic potency in bile from
      male fish was markedly elevated in Mar Menor lagoon (234.8+/-5.7 pg E2EQ/MUl),
      and further research will be necessary to explain whether the presence of natural
      and synthetic-hormones in the lagoon contributed to this finding. Values of
      approximately 15-16E2EQ pg/mg bile can be regarded as preliminary baseline levels
      of bile estrogenicity in male red mullet from the western Mediterranean Sea.

PMID- 23537583
TI  - Dysfunctions of the translational machinery in digestive glands of mussels
      exposed to mercury ions.
AB  - Mercury is an element naturally occurring in the biosphere, but is also released
      into the environment by human activities, such as mining, smelting, and
      industrial discharge. Mercury is a biologically harmful element and any exposure
      of living organisms mainly due to contamination, can cause severe or even lethal
      side effects. In every form detected, elemental, inorganic, or organic, mercury
      exhibits toxicity associated with induced oxidative stress. Although the
      genotoxicity of mercury has been well demonstrated in mussels, little is known
      about its toxic effects on the translational machinery at the molecular level. To
      investigate possible effects, we exposed the common mussel Mytilus
      galloprovincialis in seawater supplemented by 30 MUg/L Hg2+ for 15 days. We
      observed that Hg2+ was significantly accumulated in the digestive glands of
      mussels, reaching a level around 80 MUg/g tissue (dry weight) at the 15th day of
      exposure. Exposure of mussels to Hg2+ resulted in failure of redox homeostasis,
      as reflected on lipid peroxidation levels and superoxide dismutase activity in
      glands, and micronucleus frequency in gills. Extracts from digestive glands after
      15-day exposure to Hg2+ exhibited decreased tRNA aminoacylation ability and,
      moreover, a 70% reduction in the ability of 40S ribosomal subunits to form the
      48S initiation ribosomal complex. A similar reduction was detected in the ability
      of ribosomes to translocate peptidyl-tRNA from the A-site to the P-site, an
      observation coinciding with the notion that regulation of protein synthesis by
      Hg2+ mainly occurs at the initiation and elongation stages of translation. A-site
      binding, peptidyl transferase activity, and termination of peptide chain
      synthesis underwent less pronounced but measurable reductions, a finding which
      explains why poly(Phe)-synthesis in ribosomes isolated from exposed mussels is
      reduced by 70%. In conclusion, Hg2+ apart from being a genotoxic ion acts as a
      modulator of protein synthesis in mussels, an observation probably related with
      its ability to induce oxidative stress.

PMID- 23537584
TI  - Is real time 3D transesophageal echocardiography a feasible approach to detect
      coronary ostium during transapical aortic valve implantation?
AB  - OBJECTIVE: Transapical aortic valve implantation (TAVI) may lead to obstruction
      of coronary arteries during deployment. To prevent this, it is essential to
      determine the distance of the coronary ostium to the aortic annulus prior to
      valve placement. Multidetector computed tomography (MDCT) commonly is used to
      determine these measurements, but even marginal exposure to contrast agents can
      result in acute kidney injury in this high-risk group of multi-morbid patients.
      The aim of the study was to determine the feasibility of real-time 3D
      transesophageal echocardiography (RT 3D TEE) as the first-choice technique for
      noninvasive evaluation of the coronary ostium during TAVI. DESIGN: Retrospective
      study. SETTING: University hospital. INTERVENTIONS: Fifty patients underwent MDCT
      the evening before surgery. RT 3D TEE was performed intraoperatively before valve
      deployment. The dataset from both of these examinations was digitally stored and
      evaluated. MDCT was performed in nonanesthetized patients; however, in the RT 3D
      TEE group, general anesthesia was established. MEASUREMENTS AND MAIN RESULTS: The
      distances from the right coronary artery and the left coronary artery ostium were
      measured retrospectively. Bland-Altman Plots and linear regression analysis
      showed excellent correlation between the 2 methodologies; intraobserver and
      interobserver variance were calculated using analysis of variance. Krippendorff's
      alpha indicated excellent agreement between the 2 observers (0.96 and 0.98) as
      well as between RT 3D TEE and MDCT (0.97 and 0.98). CONCLUSIONS: The observations
      showed that RT 3D TEE reliably can measure the coronary ostium distance from the
      aortic annulus. It is feasible and an alternative method for evaluating these
      measurements and thereby preventing contrast exposure during MDCT, which may
      jeopardize the safety of patients with pre-existing renal disease.

PMID- 23537586
TI  - Effect of nitric oxide inhalation on gas exchange in acute severe pneumonia.
AB  - Inhaled nitric oxide (NO) causes selective pulmonary vasodilatation and may
      improve gas exchange. The study was aimed to evaluate the acute effects of
      inhaled NO on pulmonary gas exchange in severe unilateral pneumonia, where
      hypoxemia results from increased intrapulmonary shunt. We studied 8 patients
      without preexisting lung disease (59+/-18 yr; 4M/4F) with early unilateral severe
      pneumonia and respiratory failure. Pulmonary and systemic hemodynamics and gas
      exchange, including ventilation-perfusion (V;A/Q;) distributions, were measured
      at baseline and while breathing 5 and 40 parts per million (ppm) of NO. Inhaled
      NO caused a dose-dependent fall in pulmonary vascular resistance (by 12% and 21%,
      with 5 and 40ppm, respectively; p<0.01, each) and improvement of PaO2 (by 25% and
      23%; p<0.05, each), owing to the reduction of intrapulmonary shunt (by 23% and
      27%; p<0.05, each), without changes in the amount of perfusion to low V;A/Q;
      ratio alveolar units. Patients with greater baseline intrapulmonary shunt
      exhibited greater improvement in arterial oxygenation (r(2)=0.55, p<0.05). We
      conclude that low doses of inhaled NO improve pulmonary gas exchange in acute
      severe pneumonia.

PMID- 23537585
TI  - WEE1 tyrosine kinase, a novel epigenetic modifier.
AB  - The cell cycle requires cells to duplicate their chromatin, DNA, and histones,
      while retaining a subset of epigenetic marks, in a highly coordinated manner. The
      WEE1 kinase was identified as an important regulator during S phase, preventing
      entry into mitosis until DNA replication has been completed. Interestingly, WEE1
      has also emerged as a key player in regulating histone synthesis. It
      phosphorylates histone H2B at tyrosine 37 in the nucleosomes found upstream of
      the histone gene cluster, and this suppresses histone transcription in late S
      phase. These observations highlight a dual role for WEE1 as both a mitotic
      gatekeeper and a surveyor of chromatin synthesis, providing a direct link between
      epigenetics and cell-cycle progression. Importantly, this link has implications
      for the design of novel epigenetic inhibitors targeting cancers that display
      elevated expression of this kinase. 

PMID- 23537587
TI  - Changes in levels of biomarkers of exposure observed in a controlled study of
      smokers switched from conventional to reduced toxicant prototype cigarettes.
AB  - Reduced toxicant prototype (RTP) cigarettes with substantially reduced levels of
      tobacco smoke toxicants have been developed. Evaluation of these prototype
      cigarettes included measurement of biomarkers of exposure (BoE) to toxicants in
      smokers switched from conventional cigarettes to the RTPs. A 6-week single
      blinded randomised controlled study with occasional clinical confinement was
      conducted ( TRIAL REGISTRATION: ISRCTN7215735). All smoking subjects smoked a
      conventional cigarette for 2-weeks. Control groups continued to smoke the
      conventional cigarette while test groups switched to one of three RTP designs.
      Clinical confinement and additional assessments were performed for all smoking
      groups after 2 and 4-weeks. A non-smoker group provided background levels of BoE.
      On average, smokers switched to RTPs with reduced machine yields of toxicants had
      reduced levels of corresponding BoEs. For vapour phase toxicants such as acrolein
      and 1,3-butadiene reductions of ?70% were observed both in smoke chemistry and
      BoEs. Reductions in particulate phase toxicants such as tobacco-specific
      nitrosamines, aromatic amines and polyaromatic hydrocarbons depended upon the
      technologies used, but were in some cases ?80% although some increases in other
      particulate phase toxicants were observed. However, reductions in BoEs
      demonstrate that it is possible to produce prototype cigarettes that reduce
      exposure to toxicants in short-term use.

PMID- 23537588
TI  - Strategies to reduce the risk of iatrogenic illness in complex older adults.
AB  - Older patients are particularly vulnerable to adverse drug reactions (ADRs)
      because age is associated with changes in pharmacokinetics and pharmacodynamics
      that may alter drug metabolism. In addition, other conditions, commonly observed
      in older adults, may increase the risk of ADRs in the older population (including
      polypharmacy, comorbidity, cognitive and functional limitations). ADRs in older
      adults are frequently preventable, suggesting that screening and prevention
      programmes aimed at reducing the rate of iatrogenic illness are necessary in this
      population. The present study reviews available approaches that may be used to
      screen and prevent the occurrence of ADRs in older adults, including medication
      review, avoiding the use of potentially inappropriate medications, computer-based
      prescribing systems and comprehensive geriatric assessment. Available evidence on
      these approaches is mixed and controversial, and none of them showed a clear
      beneficial effect on patients' health outcomes. Limitation of these interventions
      is the lack of standardisation, and these differences may give reason for the
      variability of the results documented in randomised clinical studies.
      Interestingly, most of the available research is focused on a single intervention
      targeting either clinical or pharmacological factors causing ADRs. When these
      approaches are combined, positive effects on patients health outcomes can be
      shown, suggesting that integration of skills from different health care
      professionals is needed to address medical complexity of the older adults. The
      challenge for future research is to integrate valuable information obtained by
      existing instruments and methodologies in a complete and global approach
      targeting all potential factors involved in the onset of ADRs.

PMID- 23537589
TI  - Predictors of patterns of change in health-related quality of life in older women
      over 7 years: evidence from a prospective cohort study.
AB  - BACKGROUND: the evaluation of the determinants of change over time in health
      related quality of life (HR-QoL) in older people is limited. This study aims to
      identify patterns of change in HR-QoL over 7 years and their determinants using
      data from the British Women's Heart and Health Study, a representative sample of
      older women (n = 4286). METHODS: longitudinal latent class analysis was used to
      identify subpopulations of women with similar HR-QoL trajectories from 1999-2000
      to 2007. HR-QoL was measured using the EQ-5D. Multivariate multinomial logistic
      regression was used to model the association of identified trajectories with
      baseline predictors after multiple imputation of missing data. RESULTS: four
      distinct EQ-5D trajectories were suggested: high (19% of women), high decline
      (22%), intermediate (42%) and low decline (16%). Prevalent arthritis (OR = 13.4;
      95% CI: 8.8, 20.5), diabetes (OR = 4.6; 95% CI: 1.5, 14.2) and obesity (OR = 3.9;
      95% CI: 2.5, 6.0) were the strongest predicting health conditions of adverse
      changes in HR-QoL and physical activity the strongest predicting lifestyle factor
      (OR = 2.8; 95% CI: 2.0, 3.9). CONCLUSIONS: findings suggest that older women
      without obesity or pre-existing health conditions who undertake more physical
      activity are more likely to experience high HR-QoL, reinforcing the importance of
      these factors for healthy ageing.

PMID- 23537590
TI  - Regulation of phenylalanine hydroxylase: conformational changes upon
      phosphorylation detected by H/D exchange and mass spectrometry.
AB  - The enzyme phenylalanine hydroxylase catalyzes the hydroxylation of excess
      phenylalanine in the liver to tyrosine. The enzyme is regulated allosterically by
      phenylalanine and by phosphorylation of Ser16. Hydrogen/deuterium exchange
      monitored by mass spectrometry has been used to gain insight into any structural
      change upon phosphorylation. Peptides in both the catalytic and regulatory
      domains show increased deuterium incorporation into the phosphorylated protein.
      Deuterium is incorporated into fewer peptides than when the enzyme is activated
      by phenylalanine, and the incorporation is slower. This establishes that the
      conformational change upon phosphorylation of phenylalanine hydroxylase is
      different from and less extensive than that upon phenylalanine activation.

PMID- 23537591
TI  - Anaphylactic reaction to bell pepper (Capsicum annuum) in a patient with a latex
      fruit syndrome.

PMID- 23537592
TI  - Drug allergy in haematopoietic stem cell transplantation.

PMID- 23537593
TI  - FEF25-75 should be carefully considered in allergic rhinitis.

PMID- 23537595
TI  - [The scientific societies and the lack of skills: a training programme in
      bariatric surgery].

PMID- 23537594
TI  - A case of a non-immunocompromised adult with fever, mononucleosis and a
      serological puzzle.

PMID- 23537596
TI  - Dissolution behavior of high strength bioresorbable glass fibers manufactured by
      continuous fiber drawing.
AB  - This article describes the dissolution behavior of three silica-based resorbable
      glasses manufactured by an industrial-type continuous fiber drawing process
      yielding fibers with tensile strength of 1800-2300MPa. The results of a long-term
      in vitro degradation testing of the manufactured high strength bioresorbable
      glass fibers are presented. The degradation was performed by exposing the glass
      fibers to SBF and TRIS for 26 weeks at physiological conditions at 37 degrees C.
      All fibers showed continuous resorption throughout the study and two of the
      fibers revealed bioactivity by forming a calcium phosphate (CaP) layer in SBF.

PMID- 23537597
TI  - Antioxidant and micronutrient-rich milk formula reduces lead poisoning and
      related oxidative damage in lead-exposed mice.
AB  - Lead poisoning is a global environmental disease that induces lifelong adverse
      health effects. The effect of a milk formula consisting of antioxidant of bamboo
      leaves (AOB), vitamin C (Vc), calcium lactate (CaLac), ferrous sulfate (FeSO4)
      and zinc sulfate (ZnSO4) on the reduction of lead and lead-induced oxidative
      damage in lead-exposed mice was studied. The lead-reducing effect of milk formula
      was investigated via a 7-week toxicokinetics study and a tissue distribution
      level examination. The ameliorating effect of milk formula on lead-induced
      oxidative damage was investigated. Results demonstrated current milk formula
      could effectively reduce blood lead levels (BLLs) and lead distribution levels of
      liver, kidneys, thighbones and brain in mice based on metal ion-mediated
      antagonism and chelation mechanisms. This milk formula could not only protect
      lead-susceptible tissues against lead poisoning, but also maintain normal
      absorption and distribution of essential elements in vivo. Meanwhile, current
      milk formula could prevent the reduction of delta-aminolevulinic acid dehydratase
      (delta-ALAD) activity and enhancement of free erythrocyte protoporphyrins (FEP)
      levels in blood erythrocytes of mice. Also, this formula could indirectly protect
      blood cell membranes against lead-induced lipid peroxidation. We conclude that
      current optimized milk formula effectively reduces lead poisoning and lead
      induced in vivo oxidative damage in lead-exposed mice.

PMID- 23537598
TI  - Antioxidant and anticancer activities of Chenopodium quinoa leaves extracts - in
      vitro study.
AB  - The nutraceutical potential of Chenopodium quinoa Leaves (ChL) was assessed
      through analyses of their phenolic content, elucidation of the effect of ChL
      phenolic compounds on cancer cell properties and estimation of their
      antioxidative activity, bioaccessibility and bioavailability in vitro.
      Considerable amounts of ferulic, sinapinic and gallic acids, kaempferol,
      isorhamnetin and rutin were observed in the chemical ChL extract and were linked
      with its inhibitory effect on prostate cancer cell proliferation, motility and
      cellular competence for gap junctional communication. Both extracts, chemical and
      obtained after simulated digestion, exerted an inhibitory effect on lipoxygenase
      activity, paralleled by their considerable chelating, antioxidative, antiradical
      and reducing power. These observations indicate that phenolic ChL compounds may
      exert a chemopreventive and anticarcinogenic effect on oxidative stress and ROS
      dependent intracellular signaling via synergic effects. The relatively high
      potential bioaccessibility and bioavailability of the compounds probably
      responsible for these effects demonstrates the suitability of ChL for dietary
      supplementation.

PMID- 23537599
TI  - Oxidative stress and myocardial dysfunction in young rabbits after short term
      anabolic steroids administration.
AB  - The present study focuses on the short term effects of repeated low level
      administration of turinabol and methanabol on cardiac function in young rabbits
      (4 months-old). The experimental scheme consisted of two oral administration
      periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial
      echocardiographic evaluation at the end of all three experimental periods was
      performed in all animals. Oxidative stress markers have also been monitored at
      the end of each administration period. Treated animals originally showed
      significantly increased myocardial mass and systolic cardiac output, which
      normalized at the end of the wash out period. Re-administration led to increased
      cardiac output, at the cost though of a progressive myocardial mass reduction. A
      dose-dependent trend towards impaired longitudinal systolic, diastolic and global
      myocardial function was also observed. The adverse effects were more pronounced
      in the methanabol group. For both anabolic steroids studied, the low dose had no
      significant effects on oxidative stress markers monitored, while the high dose
      created a hostile oxidative environment. In conclusion, anabolic administration
      has been found to create a possible deleterious long term effect on the growth of
      the immature heart and should be strongly discouraged especially in young human
      subjects.

PMID- 23537600
TI  - Analysis of MC-LR and MC-RR in tissue from freshwater fish (Tinca tinca) and
      crayfish (Procambarus clarkii) in tench ponds (Caceres, Spain) by liquid
      chromatography-mass spectrometry (LC-MS).
AB  - In the present study a new method has been developed and validated for detecting
      free microcystins (MCs) (MC-RR, MC-LR and MC-YR) by liquid chromatography-mass
      spectrometry (LC-MS) in the cyprinid Tinca tinca and in the crayfish Procambarus
      clarkii collected from three ponds in Extremadura (Spain) where the presence of
      the cyanobacteria species Microcystis aeruginosa and Anabaena spiroides has been
      confirmed. Once the method had been validated, free MCs were determined in fish
      (tench, T. tinca) and crayfish from different ponds in order to understand how
      they are bioaccumulated through the food web. MCs were not detected in any of the
      fish samples analyzed. It was confirmed that P. clarkii accumulated MCs in their
      tissues without losing their organoleptic characteristics, with MC-LR (2.3-18.1
      MUg MC-LR/g body weight) being the predominant MC variant detected in all the
      crayfish samples. MC-RR was measured in 50% of the samples analyzed, ranging
      between 1.4 and 7.8 MUg MC-RR/g body weight and no MC-YR was detected. The
      results indicated that crayfish can accumulate free MCs in higher quantities than
      tench that live in ponds contaminated by toxic cyanobacteria species, and
      emphasized the need for regular monitoring if the health risks associated with
      their consumption are to be avoided.

PMID- 23537601
TI  - Lead, mercury, and cadmium in blood and their relation to diet among Swedish
      adults.
AB  - The aim of the present study was to examine the body burden of lead (Pb), mercury
      (Hg), and cadmium (Cd) in blood among Swedish adults and the association between
      blood levels, diet and other lifestyle factors. The study was based on a subgroup
      (n=273) of the national survey Riksmaten 2010-2011 (4-day food records and
      questionnaire). Lead, Hg, and Cd were measured in whole blood, and Cd
      additionally in urine, by mass or fluorescence spectrometry methods. The median
      values (5-95th percentiles) of the metals in blood were as follows; Pb: 13.4 (5.8
      28.6) MUg/L, Hg: 1.13 (0.31-3.45) MUg/L, and Cd: 0.19 (0.09-1.08) MUg/L. All
      three metals increased with increasing age. Lead levels in blood were positively
      associated with intakes of game and alcohol, Hg was related to fish intake, and
      blood Cd related to smoking and low iron stores and to a low meat intake. Body
      burdens of the studied metals were generally below health based reference values,
      but several individuals had blood Pb levels above the reference point for
      possible nephrotoxic and developmental neurotoxic effects. As health effects
      cannot be excluded, individuals with high Pb exposure should aim at decreasing
      their body burden, both from food and from other exposure routes.

PMID- 23537602
TI  - Apraxia of tool use: more evidence for the technical reasoning hypothesis.
AB  - Various distinct cognitive processes such as semantic memory, executive planning
      or technical reasoning have been shown to support tool use. The aim of this study
      is to investigate the relationship between these processes. To do so, a large
      apraxia battery was submitted to 16 patients with left brain-damage (LBD) and
      aphasia and 19 healthy controls. The battery included: classical apraxia tests
      (Pantomime of Tool Use and Single Tool Use), familiar and novel tool use tests
      (Tool-Object Pairs and Sequential Mechanical Problem-Solving), semantic memory
      tests (Recognition of tool utilization gestures and Functional and Categorical
      Associations) as well as the Tower Of London. The Sequential Mechanical Problem
      Solving task is a new task which permits the evaluation of pre-planning in
      unusual tool use situations. In this task as well as in the Tool-Object Pairs
      task, participants solved a tool use problem in a Choice and a No-Choice
      condition to examine the effect of tool selection. Globally, left brain damaged
      patients were impaired as compared to controls. We found high correlations in
      left brain damaged patients between performances on classical apraxia tests,
      familiar and novel tool use tests and Functional and Categorical Associations but
      no significant association between these performances and Tower Of London or
      Recognition of tool utilization gestures. Furthermore, the two conditions (Choice
      and No-Choice) of Tool-Object Pairs and Sequential Mechanical Problem-Solving
      were associated. In sum, all tasks involving tool use are strongly associated in
      LBD patients. Moreover, the ability to solve sequential mechanical problems does
      not depend on executive planning. Also, tool use appears to be associated with
      knowledge about object function but not with knowledge about tool manipulation.
      Taken together, these findings indicate that technical reasoning and, to a lesser
      extent, semantic memory may both play an important role in tool use. 

PMID- 23537603
TI  - Cardiovascular risk factors and complications associated with albuminuria and
      impaired renal function in insulin-treated diabetes.
AB  - AIMS: To establish the association between albuminuria and cardiovascular risk
      factors as well as micro- and macrovascular complications in type 1 and insulin
      treated type 2 diabetes, both in the presence and in the absence of reduced
      estimated glomerular filtration rate (eGFR). METHODS: Cross-sectional study
      including 7640 insulin-treated diabetic patients (33% type 1) treated in
      specialist diabetes centers. Albuminuria was defined as >=30 mg/g, 20 mg/L, 20
      MUg/min or 30 mg/24 h. Reduced eGFR was defined as <60 mL/min/1.73 m(2) (CKD-EPI
      equations). RESULTS: Albuminuria, reduced eGFR or a combination was more
      prevalent in type 2 (21.5%, 15.9% and 16.5%) than in type 1 diabetes (16.1%, 4.7%
      and 4.0%, all P < 0.001 vs. type 2). Albuminuria was associated with poorer
      control of blood pressure, blood lipids and glycemia as well as higher prevalence
      of retinopathy and macrovascular disease, regardless of preserved/reduced eGFR or
      diabetes type. Reduced eGFR was associated with higher prevalence of micro- and
      macrovascular complications especially in type 2 diabetes. Combined presence of
      albuminuria and reduced eGFR was associated with the worst cardiovascular
      outcomes. CONCLUSIONS: Albuminuria and impaired renal function are prevalent in
      type 1 and insulin-treated type 2 diabetes. Albuminuria, but also
      normoalbuminuric renal impairment, is associated with micro- and macrovascular
      complications.

PMID- 23537604
TI  - Can we reverse the rising tide of compulsory admissions?

PMID- 23537605
TI  - Community treatment orders for patients with psychosis (OCTET): a randomised
      controlled trial.
AB  - BACKGROUND: Compulsory supervision outside hospital has been developed
      internationally for the treatment of mentally ill people following widespread
      deinstitutionalisation but its efficacy has not yet been proven. Community
      treatment orders (CTOs) for psychiatric patients became available in England and
      Wales in 2008. We tested whether CTOs reduce admissions compared with use of
      Section 17 leave when patients in both groups receive equivalent levels of
      clinical contact but different lengths of compulsory supervision. METHODS: OCTET
      is a non-blinded, parallel-arm randomised controlled trial. We postulated that
      patients with a diagnosis of psychosis discharged from hospital on CTOs would
      have a lower rate of readmission over 12 months than those discharged on the pre
      existing Section 17 leave of absence. Eligible patients were those involuntarily
      admitted to hospital with a diagnosis of psychosis, aged 18-65 years, who were
      deemed suitable for supervised outpatient care by their clinicians. Consenting
      patients were randomly assigned (1:1 ratio) to be discharged from hospital either
      on CTO or Section 17 leave. Randomisation used random permuted blocks with
      lengths of two, four, and six, and stratified for sex, schizophrenic diagnosis,
      and duration of illness. Research assistants, treating clinicians, and patients
      were aware of assignment to randomisation group. The primary outcome measure was
      whether or not the patient was admitted to hospital during the 12-month follow-up
      period, analysed with a log-binomial regression model adjusted for stratification
      factors. We did all analyses by intention to treat. This trial is registered,
      number ISRCTN73110773. FINDINGS: Of 442 patients assessed, 336 patients were
      randomly assigned to be discharged from hospital either on CTO (167 patients) or
      Section 17 leave (169 patients). One patient withdrew directly after
      randomisation and two were ineligible, giving a total sample of 333 patients (166
      in the CTO group and 167 in the Section 17 group). At 12 months, despite the fact
      that the length of initial compulsory outpatient treatment differed significantly
      between the two groups (median 183 days CTO group vs 8 days Section 17 group,
      p<0.001) the number of patients readmitted did not differ between groups (59
      [36%] of 166 patients in the CTO group vs 60 [36%] of 167 patients in the Section
      17 group; adjusted relative risk 1.0 [95% CI 0.75-1.33]). INTERPRETATION: In well
      coordinated mental health services the imposition of compulsory supervision does
      not reduce the rate of readmission of psychotic patients. We found no support in
      terms of any reduction in overall hospital admission to justify the significant
      curtailment of patients' personal liberty. FUNDING: National Institute of Health
      Research.

PMID- 23537606
TI  - Clinical outcomes of Joint Crisis Plans to reduce compulsory treatment for people
      with psychosis: a randomised controlled trial.
AB  - BACKGROUND: The CRIMSON (CRisis plan IMpact: Subjective and Objective coercion
      and eNgagement) study is an individual level, randomised controlled trial that
      compared the effectiveness of Joint Crisis Plans (JCPs) with treatment as usual
      for people with severe mental illness. The JCP is a negotiated statement by a
      patient of treatment preferences for any future psychiatric emergency, when he or
      she might be unable to express clear views. We assessed whether the additional
      use of JCPs improved patient outcomes compared with treatment as usual. METHODS:
      Patients were eligible if they had at least one psychiatric admission in the
      previous 2 years and were on the Enhanced Care Programme Approach register. The
      study was done with 64 generic and specialist community mental health teams in
      four English mental health care provider organisations (trusts). Hypotheses
      tested were that, compared with the control group, the intervention group would
      experience: fewer compulsory admissions (primary outcome); fewer psychiatric
      admissions; shorter psychiatric stays; lower perceived coercion; improved
      therapeutic relationships; and improved engagement. We stratified participants by
      centre. The research team but not participants nor clinical staff were masked to
      allocation. This study is registered with ClinicalTrials.gov, number
      ISRCTN11501328. FINDINGS: 569 participants were randomly assigned (285 to the
      intervention group and 284 to the control group). No significant treatment effect
      was seen for the primary outcome (56 [20%] sectioned in the control group and 49
      [18%] in the JCP group; odds ratio 0.90 [95% CI 0.58-1.39, p=0.63]) or any
      secondary outcomes, with the exception of an improved secondary outcome of
      therapeutic relationships (17.3 [7.6] vs 16.0 [7.1]; adjusted difference -1.28
      [95% CI -2.56 to -0.01, p=0.049]). Qualitative data supported this finding.
      INTERPRETATION: Our findings are inconsistent with two earlier JCP studies, and
      show that the JCP is not significantly more effective than treatment as usual.
      There is evidence to suggest the JCPs were not fully implemented in all study
      sites, and were combined with routine clinical review meetings which did not
      actively incorporate patients' preferences. The study therefore raises important
      questions about implementing new interventions in routine clinical practice.
      FUNDING: Medical Research Council UK and the National Institute for Health
      Research.

PMID- 23537607
TI  - Chemotherapy-related neuropathic symptoms and functional impairment in adult
      survivors of extracranial solid tumors of childhood: results from the St. Jude
      Lifetime Cohort Study.
AB  - OBJECTIVES: To ascertain prevalence of peripheral sensory and motor neuropathy,
      and to evaluate impairments in relation to function. DESIGN: St. Jude Lifetime
      Cohort Study, a clinical follow-up study designed to evaluate adverse late
      effects in adult survivors of childhood cancer. SETTING: A children's research
      hospital. PARTICIPANTS: Eligibility required treatment for an extracranial solid
      malignancy between 1962 and 2002, age >= 18 years, >= 10 years postdiagnosis, and
      no history of cranial radiation. Survivors (N=531) were included in the
      evaluation with a median age of 32 years and a median time from diagnosis of 25
      years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary exposure
      measures were cumulative doses of vinca-alkaloid and platinum-based
      chemotherapies. Survivors with scores >= 1 on the sensory subscale of the
      Modified Total Neuropathy Score were classified with prevalent sensory
      impairment. Those with sex-specific z scores of <=-1.3 for dorsiflexion strength
      were classified with prevalent motor impairment. Participants completed the 6
      minute walk test (endurance), the Timed Up & Go test (mobility), and the Sensory
      Organization Test (balance). RESULTS: The prevalence of sensory and motor
      impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was
      associated with an increased risk of motor impairment (adjusted odds ratio
      [OR]=1.66; 95% confidence interval [CI], 1.04-2.64) without evidence for a dose
      response. Platinum exposure was associated with increased risk of sensory
      impairment (adjusted OR=1.62; 95% CI, .97-2.72) without evidence of a dose
      response. Sensory impairment was associated with poor endurance (OR=1.99; 95% CI,
      .99-4.0) and mobility (OR=1.65; 95% CI, .96-2.83). CONCLUSIONS: Vincristine and
      cisplatin exposure may increase risk for long-term motor and sensory impairment,
      respectively. Survivors with sensory impairment are at increased risk for
      functional performance limitations.

PMID- 23537608
TI  - Impact of the clinical practice guideline for preservation of upper limb function
      on transfer skills of persons with acute spinal cord injury.
AB  - OBJECTIVES: To describe the development of a strict education protocol to
      implement the clinical practice guideline "Preservation of Upper Limb Function
      Following Spinal Cord Injury" into a clinical setting, and evaluate the effect of
      the protocol on transfer quality. DESIGN: Randomized controlled trial. SETTING:
      Acute Model Spinal Cord Injury Systems rehabilitation facility and community.
      PARTICIPANTS: Volunteer sample of full-time wheelchair users (N=70) with new
      spinal cord injuries randomized (1:1) to an intervention and standard-of-care
      group. INTERVENTION: The intervention group was educated on transfer skills with
      a structured protocol implemented by a physical and occupational therapist who
      were extensively educated on the clinical practice guidelines and current
      transfer research. The standard-of-care group received standard therapy services.
      MAIN OUTCOME MEASURES: Comparison of transfer quality evaluated by the Transfer
      Assessment Instrument at 4 time points during first year after injury. RESULTS:
      No significant differences were found between study groups. Secondary analysis
      based on type of transfer performed found that participants in the intervention
      group who performed assisted sitting pivot transfers performed higher-quality
      transfers (mean +/- SE: 9.43+/-.55) compared with the standard-of-care group
      (mean +/- SE: 7.81+/-.46) (P=.026) at 1 year after discharge. Also, participants
      who performed a dependent transfer had a higher average score across all 4 time
      points (mean +/- SE: 9.14+/-.34) compared with the standard-of-care group (mean
      +/- SE: 8.09+/-.29) (P=.019). CONCLUSIONS: For participants who perform assisted
      or dependent transfers, use of an evidenced-based, structured education program
      during acute inpatient rehabilitation has the potential to significantly improve
      the quality of transfers. Further follow-up testing is necessary with a larger
      sample size to determine the long-term effects.

PMID- 23537609
TI  - Liver receptor homologue-1 expression in ovarian epithelial and granulosa cell
      tumours.
AB  - Granulosa cell tumours of the ovary (GCT) express aromatase and produce
      oestrogens. The ovarian-specific aromatase promoter (pII) is regulated by members
      of the group 5A nuclear receptor family, SF-1 and LRH-1. Since both SF-1 and LRH
      1 are implicated in proliferation and cancer, we hypothesised that alteration in
      the expression of either or both receptors may be associated with GCT. We
      therefore determined the expression of LRH-1, SF-1 and aromatase in a cohort of
      GCT, mucinous and serous cystadenocarcinomas, and normal ovaries. LRH-1 mRNA was
      present at low level in normal ovary and serous cystadenocarcinoma, but was
      elevated approximately 30-fold in GCT, and 8-fold in mucinous cystadenocarcinoma,
      compared to normal ovary. LRH-1 protein expression was confirmed in GCT by
      immunohistochemistry. SF-1 mRNA was significantly lower that of LRH-1 in all
      samples and not significantly altered in GCT, compared to normal ovary. Aromatase
      mRNA was present at low level in normal ovary and serous and mucinous
      cystadenocarcinoma, and significantly elevated (18-fold) in GCT compared to
      normal ovary. Despite the coordinate over-expression of both LRH-1 and aromatase
      in GCT versus normal ovary, their levels did not correlate in individual
      patients; rather, aromatase expression correlated with that of SF-1. Finally,
      although both LRH-1 and SF-1 activated aromatase promoter activity in transient
      transfection studies, gel-shift and chromatin immunoprecipitation data indicated
      that SF-1, but not LRH-1, bound to the aromatase promoter. We conclude that SF-1
      regulates aromatase expression in GCT; over-expression of LRH-1 suggests that
      this receptor may be involved in the pathogenesis of GCT by mechanisms other than
      the regulation of aromatase. Its role in this disease therefore warrants further
      investigation.

PMID- 23537610
TI  - Detection of heartbeat and respiration from optical interferometric signal by
      using wavelet transform.
AB  - A novel approach for the heartbeat and respiration detection based on optical
      interferometer and wavelet transform is proposed in this paper. Optical
      interferometer is a sensitive device that detects physical elongation of optical
      fibre due to external perturbations. Mechanical activity of cardiac muscle and
      respiration reflects in interferometric signal when the interferometer is in
      contact with human body and, thus, enables unobtrusive detection of human vital
      signs. The efficiency and accuracy of the proposed approach was estimated in two
      experimental protocols. The first one collected interferometric signals from 20
      subjects during rest. In the second experiment, 10 participants cycled an
      ergometer until reaching their submaximal heart rate, and were measured
      immediately after that. Heartbeat detection results show high efficiency (99.46+/
      1.11% sensitivity, 99.60+/-1.05% precision) and accuracy (mean relative error
      (MRE) of beat-to-beat intervals 3.16+/-2.32%) for the first experiment, and
      slightly lower efficiency (96.22+/-2.96% sensitivity, 95.35+/-3.03% precision)
      and accuracy (MRE of 9.56+/-3.67%) for the second experiment. Considering
      respiration detection, high efficiency (97.64+/-7.28% sensitivity, 99.38+/-2.80%
      precision) and accuracy (MRE of intervals between respiration events 7.37+/
      7.20%) for the first experiment, and acceptable efficiency (92.05+/-6.10%
      sensitivity, 93.45+/-3.08% precision) and accuracy (MRE of 16.28+/-6.25%) for the
      second experiment confirm a practical value of proposed approaches.

PMID- 23537611
TI  - A data mining approach for diagnosis of coronary artery disease.
AB  - Cardiovascular diseases are very common and are one of the main reasons of death.
      Being among the major types of these diseases, correct and in-time diagnosis of
      coronary artery disease (CAD) is very important. Angiography is the most accurate
      CAD diagnosis method; however, it has many side effects and is costly. Existing
      studies have used several features in collecting data from patients, while
      applying different data mining algorithms to achieve methods with high accuracy
      and less side effects and costs. In this paper, a dataset called Z-Alizadeh Sani
      with 303 patients and 54 features, is introduced which utilizes several effective
      features. Also, a feature creation method is proposed to enrich the dataset. Then
      Information Gain and confidence were used to determine the effectiveness of
      features on CAD. Typical Chest Pain, Region RWMA2, and age were the most
      effective ones besides the created features by means of Information Gain.
      Moreover Q Wave and ST Elevation had the highest confidence. Using data mining
      methods and the feature creation algorithm, 94.08% accuracy is achieved, which is
      higher than the known approaches in the literature.

PMID- 23537613
TI  - Improving the detection of ventricular tachycardia: a smarter implantable loop
      recorder.

PMID- 23537612
TI  - Antimicrobial resistance in Libya: 1970-2011.
AB  - Resistance to antimicrobial agents is a major health problem that affects the
      whole world. Providing information on the past state of antimicrobial resistance
      in Libya may assist the health authorities in addressing the problem more
      effectively in the future. Information was obtained mainly from Highwire Press
      (including PubMed) search for the period 1970-2011 using the terms 'antibiotic
      resistance in Libya', 'antimicrobial resistance in Libya', 'tuberculosis in
      Libya', and 'primary and acquired resistance in Libya' in title and abstract.
      From 1970 to 2011 little data was available on antimicrobial resistance in Libya
      due to lack of surveillance and few published studies. Available data shows high
      resistance rates for Salmonella species in the late 1970s and has remained high
      to the present day. High prevalence rates (54-68%) of methicillin-resistant
      Staphylococcus aureus (MRSA) were reported in the last decade among S. aureus
      from patients with burns and surgical wound infections. No reports were found of
      vancomycin-resistant S. aureus (VRSA) or vancomycin-intermediate-resistant S.
      aureus (VISA) using standard methods from Libya up to the end of 2011. Reported
      rates of primary (i.e. new cases) and acquired (i.e. retreatment cases) multidrug
      resistant tuberculosis (MDR-TB) from the eastern region of Libya in 1971 were
      16.6 and 33.3% and in 1976 were 8.6 and 14.7%, in western regions in 1984-1986
      were 11 and 21.5% and in the whole country in 2011 were estimated at 3.4 and 29%,
      respectively. The problem of antibiotic resistance is very serious in Libya. The
      health authorities in particular and society in general should address this
      problem urgently. Establishing monitoring systems based on the routine testing of
      antimicrobial sensitivity and education of healthcare workers, pharmacists, and
      the community on the health risks associated with the problem and benefits of
      prudent use of antimicrobials are some steps that can be taken to tackle the
      problem in the future.

PMID- 23537614
TI  - Refractory ventricular fibrillation during bi-ventricular implantable
      cardioverter defibrillator implantation: a case report of successful
      cardioversion only with a left ventricular defibrillator lead.

PMID- 23537615
TI  - Bleeding risk during oral anticoagulation therapy for atrial fibrillation.

PMID- 23537616
TI  - The influence of endometriosis-related symptoms on work life and work ability: a
      study of Danish endometriosis patients in employment.
AB  - OBJECTIVE: Little is known about the implications of endometriosis on women's
      work life. This study aimed at examining the relation between endometriosis
      related symptoms and work ability in employed women with endometriosis. STUDY
      DESIGN: In a cohort study, 610 patients with diagnosed endometriosis and 751
      reference women completed an electronic survey based on the Endometriosis Health
      Profile 30-questionnaire and the Work Ability Index (short form). Percentages
      were reported for all data. Binary and multivariate logistic regression analyses
      were used to assess risk factors for low work ability. The level of statistical
      significance was set at p<0.025 in all analyses. RESULTS: In binary analyses a
      diagnosis of endometriosis was associated with more sick days, work disturbances
      due to symptoms, lower work ability and a wide number of other implications on
      work life in employed women. Moreover, a higher pain level and degree of symptoms
      were associated with low work ability. Full regression analysis indicated that
      tiredness, frequent pain, a higher daily pain level, a higher number of sick days
      and feeling depressed at work were associated with low work ability. A long delay
      from symptom onset to diagnosis was associated with low work ability.
      CONCLUSIONS: These data indicate a severe impact of endometriosis on the work
      ability of employed women with endometriosis and add to the evidence that this
      disease represents a significant socio-economic burden.

PMID- 23537617
TI  - Does medical debulking with gonadotrophin-releasing hormone agonist facilitate
      vaginal hysterectomy with a moderate enlarged uterus? A randomized control study.
AB  - BACKGROUND: Vaginal hysterectomy is considered the method of choice for removal
      of the uterus but most gynecologists still prefer the abdominal route for removal
      of benign uteri >14 weeks in size. Conversion of an abdominal to a potential
      vaginal hysterectomy by uterine size reduction would be advantageous.
      Gonadotrophin-releasing hormone (GnRH) agonists can reduce uterine bulk by up to
      50%. OBJECTIVE: To evaluate the efficacy of the preoperative administration of a
      GnRH agonist for women with enlarged non-prolapsing uteri in order to facilitate
      vaginal hysterectomy, in comparison with patients with enlarged uteri who
      underwent direct total abdominal hysterectomy (TAH) for the same indication
      (menorrhagia). STUDY DESIGN: Randomized controlled study. Women scheduled for
      hysterectomy for menorrhagia with a non-prolapsing uterus of >=14 weeks size (by
      clinical and sonographic assessments) were offered a trial of vaginal
      hysterectomy after pre-treatment with a GnRH agonist (goserelin) for 3 months
      (study group=Group 1=40). A group of women with uteri of comparable size who
      underwent abdominal hysterectomy for similar indications served as controls
      (Group 2=40). Pre- and post-operative data such as hemoglobin, myoma size,
      uterine weight, duration of procedure and complications, pain score and length of
      hospital stay were collected prospectively. RESULTS: The weight of the uterine
      specimen was significantly lower in Group 1 (511.7+/-217g) compared to Group 2
      (736.8+/-212g); P<0.001. The mean objective decrease in clinical uterine bulk
      preoperatively in Group 1 was 20.1%. The duration of surgery was nearly 1.5 times
      as long in vaginal (119.6+/-41.7min) compared to abdominal hysterectomy (81.1+/
      34.1min), P<0.001, but analgesia use and the length of inpatient stay were
      significantly lower in Group 1 (2.6+/-1.3 days) compared to Group 2 (4.12+/-1.7
      days), P<0.001. There was no significant difference between the two groups as
      regards the rate of occurrence of surgical complications. CONCLUSIONS: In women
      with >=14 week size uteri, treatment with a GnRH agonist reduces uterine size
      sufficiently to allow safe vaginal hysterectomy. Although duration of surgery was
      longer, women who underwent vaginal hysterectomy required less analgesia and had
      a shorter inpatient stay.

PMID- 23537618
TI  - Association between knowledge and attitudes of school nurses towards epilepsy and
      the risk of accidents in Greek schools.
AB  - School nurses have the ability to enhance the knowledge and tolerance of an
      entire community and to form more positive and sensitized attitudes to future
      adults. The aim of this study was to investigate the relationship between the
      knowledge and attitudes of nurses and the frequency of accidents caused by
      epilepsy in Greek schools. Our sample consisted of 306 school nurses from all
      over the country. It was observed that the knowledge of school nurses on epilepsy
      was quite high, although there were specific aspects that raise concerns on their
      preparedness to respond to seizure-related emergencies, while their attitudes,
      although positive, still need improvement. Accidents caused by epilepsy were
      reported by half of the nurses, and prevention was considered of major
      importance. Therefore, organized continuous education programs and clear
      guidelines by the responsible authorities would help school nurses provide better
      services to students with epilepsy.

PMID- 23537620
TI  - Effects of antipsychotic drugs on the duration of interictal psychotic episodes
      in patients with epilepsy.
AB  - Treatment protocols for interictal psychosis (IIP) of patients with epilepsy have
      not yet been established. We aimed to clarify the effects of antipsychotic drugs
      (APDs) on duration of IIP episodes. We studied 393 IIP episodes in 200 patients
      with epilepsy in accordance with our empirical treatment protocol. The duration
      of all the episodes and APD treatments were reviewed. Antipsychotic drugs were
      used in 338 episodes and not used in 55 episodes (non-APD group). The APDs used
      in the treatment of IIP episodes were divided into the following three groups:
      first-generation APDs (FAPD, n=252), second-generation APDs (SAPD, n=44), and the
      combination of first- and second-generation APDs (CAPD, n=42). The non-APD group
      showed a significantly shorter episode duration than did the APD group (F=6.05,
      p=0.014). Among the 3 APD groups (FAPD, SAPD, and CAPD), there was a significant
      difference in duration of IIP episode (F=8.65, p=0.000). Whereas the duration of
      episodes was significantly longer in the CAPD group than in the other two groups,
      it was not significantly different between the FAPD and SAPD groups. Our findings
      further to clarify the nature of IIP and add further perspectives on treatment
      protocols for IIP.

PMID- 23537619
TI  - Attention impairment in childhood absence epilepsy: an impulsivity problem?
AB  - Although attention problems have often been described in children with childhood
      absence epilepsy (CAE), the use of different methodological approaches,
      neuropsychological tests, and heterogeneous experimental groups has prevented
      identification of the selective areas of attention deficit in this population. In
      this study, we investigated several components of attention in children with CAE
      using a unique computerized test battery for attention performance. Participants
      included 24 patients with CAE and 24 controls matched for age and sex. They were
      tested with a computerized test battery, which included the following tasks:
      selective attention, impulsivity, focused attention, divided attention,
      alertness, and vigilance. Compared with healthy controls, patients with CAE made
      more commission errors in the Go/No-Go task and more omission errors in the
      divided attention task. Childhood absence epilepsy patients also showed decreased
      reaction times in measures of selective attention and a great variability of
      reaction times in alertness and Go/No-Go tasks. Our findings suggest that
      patients with CAE were impaired in tonic and phasic alertness, divided attention,
      selective attention, and impulsivity.

PMID- 23537621
TI  - Episodes of status epilepticus in young adults: etiologic factors, subtypes, and
      outcomes.
AB  - The aim of this study was to evaluate the type, duration, etiology, treatment,
      and outcome of status epilepticus (SE) episodes, among patients aged 16-50 years.
      A total of 101 SE episodes in 88 young adult patients fulfilled our criteria. The
      mean age was 32 years. Status epilepticus episodes were most frequently observed
      in patients 21-30 years of age. A total of 53% of the patients were male, and 57%
      had pre-existing epilepsy. Seventy of the 101 episodes were convulsive SE. The
      most common etiology was withdrawal of or change in antiepileptic drugs (AEDs),
      seen in 31% of the SE episodes. This study included treatment of SE with
      traditional AEDs. Sixty-six episodes were treated successfully with intravenous
      infusion of 18-mg/kg phenytoin, and six episodes were treated with 10-mg/kg
      phenytoin. A total of 28% of the SE episodes remained refractory to first-line
      treatment, which was related to the duration of SE and mortality. The outcome was
      death in 14% of the patients due to underlying etiologies in the hospital.

PMID- 23537622
TI  - Glucocorticoid metabolism in the developing lung: adrenal-like synthesis pathway.
AB  - Glucocorticoids (GCs) are essential to normal lung development. They participate
      in the regulation of important developmental events including morphological
      changes, and lung maturation leading to the surge of surfactant synthesis by type
      II epithelial cells. Antenatal GC is administered to mothers at risk of premature
      delivery to reduce the risk of respiratory distress syndrome (RDS). Sex
      differences were reported in RDS, in the efficiency of antenatal GC treatment
      independently of surfactant levels, and in surfactant lipid synthesis. Type II
      epithelial cell maturation is regulated by epithelial-fibroblast cell-cell
      communication and involves paracrine factors secreted by fibroblasts under the
      stimulatory effect of GC. This positive action of GC can be inhibited by
      androgens through the androgen receptor (AR) present in fibroblasts. In fact,
      lung development is regulated not only by GC and androgens but also by GC and
      androgen metabolisms within the developing lung. We recently reviewed the
      metabolism of androgens in the fetal lung [45]. Here, we review multiple aspects
      of GC metabolism in the developing lung including inactivation and re-activation
      by 11beta-HSDs, synthesis from the adrenal-like synthesis pathway expressed
      within the lung and the putative role of CRH and ACTH originating from lung in
      the regulation of this pathway. This article is part of a Special Issue entitled
      'Pregnancy and Steroids'. 

PMID- 23537623
TI  - Spatial panel analyses of alcohol outlets and motor vehicle crashes in
      California: 1999-2008.
AB  - Although past research has linked alcohol outlet density to higher rates of
      drinking and many related social problems, there is conflicting evidence of
      density's association with traffic crashes. An abundance of local alcohol outlets
      simultaneously encourages drinking and reduces driving distances required to
      obtain alcohol, leading to an indeterminate expected impact on alcohol-involved
      crash risk. This study separately investigates the effects of outlet density on
      (1) the risk of injury crashes relative to population and (2) the likelihood that
      any given crash is alcohol-involved, as indicated by police reports and single
      vehicle nighttime status of crashes. Alcohol outlet density effects are estimated
      using Bayesian misalignment Poisson analyses of all California ZIP codes over the
      years 1999-2008. These misalignment models allow panel analysis of ZIP-code data
      despite frequent redefinition of postal-code boundaries, while also controlling
      for overdispersion and the effects of spatial autocorrelation. Because models
      control for overall retail density, estimated alcohol-outlet associations
      represent the extra effect of retail establishments selling alcohol. The results
      indicate a number of statistically well-supported associations between retail
      density and crash behavior, but the implied effects on crash risks are relatively
      small. Alcohol-serving restaurants have a greater impact on overall crash risks
      than on the likelihood that those crashes involve alcohol, whereas bars primarily
      affect the odds that crashes are alcohol-involved. Off-premise outlet density is
      negatively associated with risks of both crashes and alcohol involvement, while
      the presence of a tribal casino in a ZIP code is linked to higher odds of police
      reported drinking involvement. Alcohol outlets in a given area are found to
      influence crash risks both locally and in adjacent ZIP codes, and significant
      spatial autocorrelation also suggests important relationships across geographical
      units. These results suggest that each type of alcohol outlet can have differing
      impacts on risks of crashing as well as the alcohol involvement of those crashes.

PMID- 23537624
TI  - Serving limited English proficient callers: a survey of 9-1-1 police
      telecommunicators.
AB  - INTRODUCTION: The emergency telephone number 9-1-1 serves as a lifeline to the
      public during emergencies, and first responders rely on information gathered by 9
      1-1 telecommunicators who speak with callers. Timely, accurate information from
      the telecommunicators is essential for providing appropriate care on scene.
      Language barriers can hamper these efforts and result in less efficient
      information exchange. Although 9-1-1 telecommunicators may access over-the-phone
      interpreter (OPI) services to facilitate communication, managing three-way
      communication during an emergency is challenging. Problem There is little
      published on the relationship between limited English proficient (LEP) callers
      and 9-1-1 police telecommunicators, and the role of OPI services during these
      calls. Further, little is known about effective strategies to manage such calls.
      METHODS: In King County, Washington, 9-1-1 police telecommunicators were surveyed
      about their experiences handling LEP calls and managing three-way communication
      with OPI services. The survey contained 13 multiple-choice and three open
      response questions addressing communication strategies, challenges with LEP
      callers, and three-way communication with OPI services. Goodman-Kruskal Gamma and
      chi-square tests were conducted with OPI use as the dependent variable.
      Additional analyses were conducted using stress levels as the dependent variable.
      RESULTS: Of 123 respondents, 69 (56.5%) 9-1-1 telecommunicators reported
      utilizing OPI services at least 75% of the time when receiving a call from an LEP
      caller. Further, 35 (28.7%) of these telecommunicators reported calls with LEP
      individuals as more stressful than calls with fluent English speakers. Dispatcher
      stress level during LEP calls compared with stress during calls with fluent
      English speakers was positively associated with use of OPI services (P < .01).
      Further, stress level was also positively associated with telecommunicator
      difficulties in assessing the situation with respect to officer safety (P < .01).
      Sixty-three (58.3%) of the telecommunicators described difficulties assessing the
      situation to determine the appropriate response as the biggest challenge with LEP
      callers. Additionally, 62 (53%) identified knowing their location in English as
      information LEP callers need to know prior to calling 9-1-1. CONCLUSION: These
      results highlight intervention opportunities for both 9-1-1 telecommunicators and
      LEP communities. Together, interventions such as working with LEP communities to
      educate them on best communication practices during 9-1-1 calls, and with 9-1-1
      telecommunicators to help them manage three-way communication and reduce stress
      associated with concern for officer safety may improve emergency communication
      during 9-1-1 calls.

PMID- 23537625
TI  - Effect of bacterial peptidoglycan on erythrocyte death and adhesion to
      endothelial cells.
AB  - Peptidoglycans, bacterial wall components, have previously been shown to trigger
      eryptosis, the suicidal erythrocyte death, characterized by cell shrinkage and
      cell membrane scrambling with phosphatidylserine exposure at the cell surface.
      Phosphatidylserine exposing erythrocytes adhere to the vascular wall at least
      partially by interaction of erythrocytic phosphatidylserine with endothelial CXC
      chemokine ligand 16 (CXCL16). The present study explored whether peptidoglycan
      exposure fosters the adhesion of erythrocytes to human umbilical vein endothelial
      cells (HUVEC). To this end, HUVEC were treated for 48 h with peptidoglycan (10
      MUg/ml) and CXCL16 abundance determined by confocal microscopy and FACS analysis.
      Moreover, human erythrocytes were exposed for 48 h to peptidoglycan (10 MUg/ml)
      and phosphatidylserine exposure estimated from binding of fluorescent annexin-V,
      cell volume from forward scatter in FACS analysis and erythrocyte adhesion to
      human umbilical vein endothelial cells (HUVEC) from trapping of labeled
      erythrocytes in a flow chamber. As a result, bacterial peptidoglycan exposure was
      followed by increased CXCL16 expression in HUVEC as well as erythrocyte
      shrinkage, phosphatidylserine exposure and adhesion to HUVEC under flow
      conditions at arterial shear rates. The adhesion was significantly attenuated but
      not abrogated in the presence of either, erythrocyte phosphatidylserine-coating
      annexin-V (5 MUl/ml) or CXCL16 neutralizing antibody directed against endothelial
      CXCL16 (4 MUg/ml). In conclusion, exposure to peptidoglycan increases endothelial
      CXCL16 expression and leads to eryptosis followed by phosphatidylserine- and
      CXCL16-mediated adhesion of eryptotic erythrocytes to vascular endothelial cells.

PMID- 23537626
TI  - Bidirectional myoblast-pericyte plasticity.
AB  - Microvascular pericytes are able to generate multiple mesenchymal cell types,
      including skeletal muscle myoblasts. Cappellari et al. (2013) report in this
      issue of Developmental Cell that myoblasts can return the favor by generating
      pericytes via the action of Dll4 Notch ligand and PDGF-BB.

PMID- 23537627
TI  - RNA in the loop.
AB  - Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological
      roles, particularly as cis or trans gene expression regulators. Reporting
      recently in Nature, Lai et al. (2013) show that a class of gene-activating
      lncRNAs combines two gene regulation paradigms: enhancer-directed chromosomal
      looping and RNA-mediated protein effector recruitment.

PMID- 23537628
TI  - Holding on and letting go: cadherin turnover in cell intercalation.
AB  - In zebrafish early development, blastoderm cells undergo extensive radial
      intercalations, triggering the spreading of the blastoderm over the yolk cell and
      thereby initiating embryonic body axis formation. Now reporting in Developmental
      Cell, Song et al. (2013) demonstrate a critical function for EGF-dependent E
      cadherin endocytosis in promoting blastoderm cell intercalations.

PMID- 23537629
TI  - CLASPing microtubules and auxin transport.
AB  - The role, if any, of microtubules in auxin transport is poorly understood in
      plant biology. In this issue of Developmental Cell, Ambrose et al. (2013) show
      that the microtubule binding protein CLASP regulates PIN2 auxin transporter
      trafficking and stability via Sorting Nexin1, a component of the retromer
      complex.

PMID- 23537630
TI  - Dynamin 2 potentiates invasive migration of pancreatic tumor cells through
      stabilization of the Rac1 GEF Vav1.
AB  - The large GTPase Dynamin 2 (Dyn2) is markedly upregulated in pancreatic cancer,
      is a potent activator of metastatic migration, and is required for Rac1-mediated
      formation of lamellipodia. Here we demonstrate an unexpected mechanism of Dyn2
      action in these contexts via direct binding to the Rac1 guanine nucleotide
      exchange factor (GEF) Vav1. Surprisingly, disruption of the Dyn2-Vav1 interaction
      targets Vav1 to the lysosome for degradation via an interaction with the
      cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein
      stability. Importantly, a specific mutation in Vav1 near its Dyn2-binding C
      terminal Src homology 3 (SH3) domain prevents Hsc70 binding, resulting in a
      stabilization of Vav1 levels. Dyn2 binding regulates the interaction of Vav1 with
      Hsc70 to control the stability and subsequent activity of this oncogenic GEF.
      These findings elucidate how Dyn2 activates Rac1, lamellipod protrusion, and
      invasive cellular migration and provide insight into how this specific Vav is
      ectopically expressed in pancreatic tumors.

PMID- 23537631
TI  - Endothelio-mesenchymal interaction controls runx1 expression and modulates the
      notch pathway to initiate aortic hematopoiesis.
AB  - Hematopoietic stem cells (HSCs) are produced by a small cohort of hemogenic
      endothelial cells (ECs) during development through the formation of intra-aortic
      hematopoietic cell (HC) clusters. The Runx1 transcription factor plays a key role
      in the EC-to-HC and -HSC transition. We show that Runx1 expression in hemogenic
      ECs and the subsequent initiation of HC formation are tightly controlled by the
      subaortic mesenchyme, although the mesenchyme is not a source of HCs. Runx1 and
      Notch signaling are involved in this process, with Notch signaling decreasing
      with time in HCs. Inhibiting Notch signaling readily increases HC production in
      mouse and chicken embryos. In the mouse, however, this increase is transient.
      Collectively, we show complementary roles of hemogenic ECs and mesenchymal
      compartments in triggering aortic hematopoiesis. The subaortic mesenchyme induces
      Runx1 expression in hemogenic-primed ECs and collaborates with Notch dynamics to
      control aortic hematopoiesis.

PMID- 23537632
TI  - A conserved genetic pathway determines inflorescence architecture in Arabidopsis
      and rice.
AB  - The spatiotemporal architecture of inflorescences that bear flowers determines
      plant reproductive success by affecting fruit set and plant interaction with
      pollinators. The inflorescence architecture that displays great diversity across
      flowering plants depends on developmental decisions at inflorescence meristems.
      Here we report a key conserved genetic pathway determining inflorescence
      architecture in Arabidopsis thaliana and Oryza sativa (rice). In Arabidopsis,
      four MADS-box genes, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1, SHORT VEGETATIVE
      PHASE, AGAMOUS-LIKE 24, and SEPALLATA 4 act redundantly and directly to suppress
      TERMINAL FLOWER1 (TFL1) in emerging floral meristems. This is indispensable for
      the well-known function of APETALA1 in specifying floral meristems and is coupled
      with a conformational change in chromosome looping at the TFL1 locus. Similarly,
      we demonstrate that the orthologs of these MADS-box genes in rice determine
      panicle branching by regulating TFL1-like genes. Our findings reveal a conserved
      regulatory pathway that determines inflorescence architecture in flowering
      plants.

PMID- 23537633
TI  - A sequence in the Drosophila H3-H4 Promoter triggers histone locus body assembly
      and biosynthesis of replication-coupled histone mRNAs.
AB  - Compartmentalization of RNA biosynthetic factors into nuclear bodies (NBs) is a
      ubiquitous feature of eukaryotic cells. How NBs initially assemble and ultimately
      affect gene expression remains unresolved. The histone locus body (HLB) contains
      factors necessary for replication-coupled histone messenger RNA transcription and
      processing and associates with histone gene clusters. Using a transgenic assay
      for ectopic Drosophila HLB assembly, we show that a sequence located between, and
      transcription from, the divergently transcribed H3-H4 genes nucleates HLB
      formation and activates other histone genes in the histone gene cluster. In the
      absence of transcription from the H3-H4 promoter, "proto-HLBs" (containing only a
      subset of HLB components) form, and the adjacent histone H2a-H2b genes are not
      expressed. Proto-HLBs also transiently form in mutant embryos with the histone
      locus deleted. We conclude that HLB assembly occurs through a stepwise process
      involving stochastic interactions of individual components that localize to a
      specific sequence in the H3-H4 promoter.

PMID- 23537634
TI  - Assessing the quality of epilepsy care with an electronic patient record.
AB  - PURPOSE: The American Academy of Neurology (AAN) quality indicators for epilepsy
      are designed to monitor quality, identify gaps, and ultimately drive improvements
      in clinical care. Appreciation of electronic patient records (EPR) to support
      such performance management is growing. This study aimed to demonstrate the use
      of an epilepsy-specific EPR in applying the AAN measures to objectively monitor
      clinical performance. METHOD: A sample of out-patient clinics at Beaumont
      Hospital, Dublin was benchmarked against 4 of the AAN quality indicators.
      RESULTS: 88% (142/160) of clinical encounters met the requirement to explicitly
      document seizure type and seizure frequency at each visit; aetiology or epilepsy
      syndrome was documented/updated for 58% (93/160); evidence of counselling about
      antiepileptic drug side effects was present in 34% (54/160) of records;
      counselling for women of childbearing potential was documented in 33% (18/57) of
      relevant records. CONCLUSION: The EPR makes performance monitoring efficient and
      objective. Results suggest either failure to carryout recommended clinical tasks
      or poor documentation. Whichever is the case, a baseline is provided against
      which improvement goals can be set.

PMID- 23537635
TI  - [Psychometric properties of the French version of the How I Think Questionnaire].
AB  - Certain research has pointed out the relative importance of cognitive distortions
      in the development of antisocial behavior. Distortions of social cognitions that
      facilitate aggression and other types of antisocial behavior have been described
      as self-serving cognitive distortions (Barriga et al., 2001 [2]). Considering the
      importance of the assessment of delinquent cognitive distortions, an instrument
      has been validated to measure self-serving cognitive distortions: the How I Think
      Questionnaire (HIT-Q, Barriga et al., 2001 [2]). Thus, the aim of the present
      study was to evaluate the convergent, discriminant and concurrent validity of a
      French version of the HIT-Q and its four dimensions (self-centered, blaming
      other, minimizing/mislabeling and assuming the worst). METHOD: A sample of 972
      French high-school students completed the Youth Psychopathic traits Inventory
      (YPI ; Andershed et al., 2002 ; Andershed et al., 2007 [26,27]) used to evaluate
      the convergent validity of the HIT-Q. To investigate discriminant validity,
      participants also completed the Sociomoral Reflection Measure-Short Form (SMR-SF
      ; Gibbs et al., 1992 [28]) and the Interpersonal Reactivity Index (IRI ; Davis,
      1983 [29]) used to assess cognitive and affective empathy. To measure antisocial
      behavior, the French versions of the Self-Reported Delinquency Questionnaire
      (SRDQ ; Le Blanc and Frechette, 1989 [22]), the Antisocial Behavior Scale (ABS ;
      Schawb-Stone et al., 1996 [23]), the Self-Reported Delinquency Behavior (SRDB ;
      Elliott and Menard, 1996 [24]) and three items of the Sexual Experiences Survey
      (SES ; Koss et al., 2007 [25]) were used. Two samples were composed based on the
      same socio-demographic (age and gender) and socio-economic characteristics and
      ethnic background. French males scoring in the upper quartile on the antisocial
      behavior total score were classified in the antisocial group (n=135) and the rest
      of the sample in the non-antisocial group (n=306). Convergent and discriminant
      validity was determined using Pearson coefficients of correlation. One-way
      analyses of variance were used for mean scores comparisons. Regression analysis
      was used to evaluate the relative contribution of self-serving cognitive
      distortions to the prediction of antisocial behavior. RESULTS: The French version
      of the HIT-Q showed acceptable reliability and validity and also a satisfying
      convergent and discriminant validity. The HIT-Q and its dimensions were
      positively and highly correlated to psychopathic traits (r=0.50 to r=0.61,
      p<0.05) ; these findings suggested a good convergent validity. The correlation
      between self-serving cognitive distortions and social moral reasoning (r=-0.23 to
      r=-0.28, p<0.05) and empathy (r=-0.13 to r=-0.20, p<0.05) appeared to be negative
      and low ; this relationship was conclusive and showed a satisfying discriminant
      validity. Mean comparison showed that participants in the antisocial group
      reported higher scores of self-serving cognitive distortions and its dimensions
      than the non-antisocial group. Self-serving cognitive distortions significantly
      predicted antisocial behavior (beta=0.58, SE=0.02, p<0.001) and explained 34% of
      the variance. DISCUSSION: The study of the convergent validity of the HIT-Q with
      the YPI as external criteria showed they were closely linked, which suggests self
      serving cognitive distortion may be the cognitive expression of psychopathic
      traits. The discriminant validity of the HIT-Q with moral reasoning and empathy
      was satisfying and similar to previous results (Larden et al., 2006 [20]). In
      concordance with previous studies, delinquent cognitive distortions appeared to
      be a significant predictor of antisocial behavior and moreover, participants in
      the antisocial group reported higher scores of self-serving cognitive distortions
      (Capuano, 2007 ; Barriga and Gibbs, 1996 ; Nas et al., 2008 [10-12]). CONCLUSION:
      The present study showed that the French version of the HIT-Q presents good
      psychometric properties.

PMID- 23537636
TI  - [Advanced directives in psychiatry: A review of the qualitative literature, a
      state-of-the-art and viewpoints].
AB  - BACKGROUND: Advance Directives are written documents, which are used for people
      to notify their preference for a future situation when they are unable to give
      their consent. In psychiatry, psychiatric advance directives (PADs) can be used
      for patients with chronic psychotic disorders such as schizophrenia, or a bipolar
      disorder. PADs give the patient an opportunity to state wishes in advance about
      his/her treatment when he/she is in an acute state of illness. PADs were
      initially developed as a way for patients to defend themselves against the power
      of the psychiatrists, but are likely to become a useful tool in psychiatric care.
      PADs may contain information about medication, non pharmaceutical devices, and
      the name of a proxy decision maker. The main objective is to reduce the number of
      compulsory hospitalisations. OBJECTIVE: This article is a qualitative review
      which carries out a state-of-the-art on the use of PADs for people with chronic
      psychotic disorders and defines suggestions to include this intervention in the
      French psychiatric context. METHOD: We used the keywords psychiatric advance
      directives, crisis card, Ulysse directives, joint crisis plan (JCP) in the
      MEDLINE database to propose a qualitative review. We selected original clinical
      studies about the use of PADs for people with psychotic disorders. RESULTS: We
      included 36 articles. The qualitative analysis identified seven main themes:
      different types of PADs, effectiveness of PADs, practical use of PADs, patient's
      views, clinician's views, economical aspects, and legal aspects. The content of
      the PADs is consistent with psychiatric standard care in nearly all cases,
      regarding medical instructions, pre-emergency interventions, non-hospital
      alternatives and non-medical personal care. Patients use their PADs to describe
      prodromal symptoms of relapse and to suggest a treatment and a hospitalisation in
      advance. PADs are not used to refuse all treatments. Patients show a strong
      interest in creating a directive and a high level of satisfaction when using it.
      They feel they have more control over their mental health problem and are more
      respected and valued as a person. Thirty-six to fifty-three percent of clinicians
      had positive opinions regarding PADs. They valued the increase of the patient's
      autonomy and the prevention of relapse, but were concerned about difficulties for
      accessing the documents, and about the lack of training of the medical teams.
      Clinicians also feared the pressure of relatives or partners on treatment
      decisions. The qualitative analysis revealed the specific benefit of the JCP, a
      particular type of PADs negotiated with the medical team, on the reduction of the
      general number of admissions. We can identify practical problems such as the lack
      of accessibility to PADs in emergency situations, and the clinician's reluctance
      to use PADs. The only economical evaluation showed a non-significant decrease in
      total costs. DISCUSSION: PADs are used in a few countries, although their
      benefits in terms of patient's perceptions and compulsory admissions are
      promising. The JCP proposes a specific clinical approach based on therapeutic
      alliance. Its creation also involves the clinician, family members and a neutral
      mediator in a negotiated process. The JCP is likely to be the most efficient PAD
      model in reducing compulsory admissions. The use of the JCP appears to be
      relevant in the context of the new French legislation, establishing outpatient
      commitment orders and could be an effective way to improve the relationships with
      patients.

PMID- 23537637
TI  - [Female intimate partner homicide: clinical and criminological issues].
AB  - BACKGROUND: Female intimate partner homicide (FIPH) is a fatal complication of
      domestic violence. The aim of this study was to describe the socio-demographic,
      clinical and criminological characteristics of male perpetrators of FIPH and to
      compare them to the perpetrators of extrafamilial homicide and the perpetrators
      of intrafamilial homicide other than FIPH. METHODS: Between 1975 and 2005, 32
      FIPH were perpetrated in the region of Angers (France), and these were compared
      to 26 intrafamilial homicides other than FIPH and to 97 extrafamilial homicides
      perpetrated in the same period, in the same region. The socio-demographic,
      clinical and criminological data were collected from psychiatric expert reports
      and medical files. RESULTS: The mean age of the FIPH perpetrators was 37.8years.
      They were professionally active, in majority as manual workers. They had a
      psychiatric record (69%), a previous criminal record (31%), and a history of
      violence against others (47%). Half of these perpetrators also had experienced a
      traumatic event before the age of 18. Compared to extrafamilial homicide
      perpetrators, FIPH perpetrators occupied more frequently a manual job and had
      prior criminal records less frequently. In the majority of cases of FIPH and
      intrafamilial homicide, the murder occurred in the evening, at the victim's home,
      and while the perpetrator was intoxicated. FIPH was mostly premeditated and was
      accompanied four times less frequently by another criminal behaviour compared to
      extrafamilial homicide. The FIPH perpetrators had more depressive symptoms and
      suicidal ideations when committing the crime and remained on the crime scene more
      often than extrafamilial homicide perpetrators who mostly attempted to flee the
      crime scene. FIPH perpetrators and extra- and intrafamilial homicide perpetrators
      were found criminally responsible in half of the cases. The socio-demographic,
      clinical and criminological characteristics of FIPH perpetrators were not
      statistically different from those of perpetrators of another intrafamilial
      homicide except that conflict preceded FIPH more frequently. CONCLUSION:
      Identification of specific features of FIPH could contribute to the early
      identification of domestic violence at risk of becoming lethal and to the
      elaboration of preventive strategies.

PMID- 23537638
TI  - [Determine the patient's position towards psychiatric care: a simple tool to
      estimate the alliance and the motivation].
AB  - OBJECTIVES: For the brief systemic therapy (BST), the evaluation of the patient's
      position towards the care is a prerequisite to psychotherapy. Three positions of
      the patient are described. The "tourist's" position: the patient claims to have
      no problem and doesn't suffer. Someone asks him to make an appointment, sometimes
      with threats. The "complaint's" position: the patient claims to suffer, but
      attributes the responsibility of this suffering to others. These two positions
      are not good for beginning a therapy. The "customer's" position differs from both
      previous positions. The "customer" considers that he has a psychological problem
      which depends on him and he is motivated in the resolution of it. In theory, the
      "customer" is more motivated and the therapeutic alliance is better. It is for
      this reason that the BST estimates the position of the patient at first, to bring
      the patient to the "customer's" position. The objective of this study is to
      assess an interview which identifies the patient's position towards the care, and
      to validate the theoretical elaborations of the brief systemic therapy. METHOD:
      The study concerns the follow-up of outpatients who consult a psychiatrist for
      the first time. The evaluation of the patients checks their position towards care
      using the Tourist-Complaint-Customer (TCC) inventory, how they suffer, the
      therapeutic alliance (scale Haq-2) and the compliance during care. The evaluation
      by the psychiatrists checks the suffering perceived, the motivation perceived and
      the diagnoses according to the DSM. RESULTS: The typology of these patients is
      made up of one half "complaint", a quarter of "tourist" and a quarter of
      "customer". The "customer's" position is correlated with the therapeutic alliance
      and the motivation perceived by the psychiatrist. The motivation perceived by the
      psychiatrist is correlated with the therapeutic alliance. These results
      correspond to the theoretical elaborations of the BST. CONCLUSION: the TCC
      inventory provides information on the motivation and the therapeutic alliance. If
      the patient is in "tourist" or "complaint" position, we recommend that the
      psychiatrist "work" to bring the patient to "customer" position. The evaluation
      of the position of the patient is simple and rich in information. We recommend
      that it be given a place in the daily practice of psychiatry.

PMID- 23537640
TI  - Role of the midpalatal suture in FEA simulations of maxillary expansion treatment
      for adolescents: a review.
AB  - The overall goal of this review was to observe how the material properties of the
      unfused midpalatal suture have been considered by researchers in finite element
      analyses of maxillary expansion. Literature from Scopus, PubMed, and Biosis were
      all considered. Upon completion of the review, it was found that researchers
      assumed the suture to be vacant, have the same elastic properties as bone, or
      have elastic properties indicative of soft tissues. By performing a simplified
      analysis of the maxilla complex during expansion, it is shown that the suture may
      have a significant influence on treatment outcome. As a result, despite valuable
      contributions from previous studies, it would be ideal to incorporate a more
      representative model of the midpalatal suture into finite element simulations.

PMID- 23537642
TI  - How to recognize the eight signs of periodontitis?
AB  - Orthodontics contributes to improving self-esteem and function. However, a common
      refrain in ortho-perio relationships states that orthodontics has no deleterious
      effects on the healthy or reduced and treated periodontium. Though supported for
      decades, this idea has now been heavily challenged by a recent systematic review
      of the literature. The conclusion of this article is unfortunately very clear.
      There is a lack of reliable evidence showing the beneficial effects of
      orthodontic treatment on periodontal health with, at best, mild adverse effects.
      How can we reduce the periodontal cost of orthodontic treatment to a minimum? How
      can we ensure that this "at best" does not turn into "at worst"? To minimize the
      adverse effects of orthodontic treatment on periodontal tissues, the orthodontist
      must be able to determine to which patients he/she can consider providing
      orthodontic treatment and those for whom prior periodontal treatment is
      mandatory. In addition to the items collected for an orthodontic diagnosis, the
      orthodontist must be able to recognize the eight signs of attachment loss.

PMID- 23537643
TI  - Identification of UHRF1/2 as new N-methylpurine DNA glycosylase-interacting
      proteins.
AB  - N-methylpurine DNA glycosylase (MPG), a DNA repair enzyme, functions in the DNA
      base excision repair (BER) pathway. Aberrant over-expression of MPG in various
      cancers suggests an important role of MPG in carcinogenesis. Identification of
      MPG-interacting proteins will help to dissect the molecular link between MPG and
      cancer development. In the present study, using immunoprecipitation coupled with
      mass spectrometry (IP/MS), we screened ubiquitin-like, containing PHD and RING
      finger domains 1 (UHRF1), an essential protein required for the maintenance of
      DNA methylation, as a MPG-interacting protein. Endogenous co-immunoprecipitation
      assay in cancer cells confirmed that UHRF1 interacted with MPG in a p53 status
      independent manner. Confocal microscopy showed that endogenous MPG and UHRF1 were
      co-localized in the nucleoplasm. Furthermore, co-immunoprecipitation assay
      indicated that UHRF2, the homolog of UHRF1, could also interact with MPG. These
      results show that MPG and the UHRF family of proteins interact, thus providing a
      functional linkage between MPG and UHRF1/2.

PMID- 23537644
TI  - Alarin but not its alternative-splicing form, GALP (Galanin-like peptide) has
      antimicrobial activity.
AB  - Alarin is an alternative-splicing form of GALP (galanin-like peptide). It shares
      only 5 conserved amino acids at the N-terminal region with GALP which is involved
      in a diverse range of normal brain functions. This study seeks to investigate
      whether alarin has additional functions due to its differences from GALP. Here,
      we have shown using a radial diffusion assay that alarin but not GALP inhibited
      the growth of Escherichia coli (strain ML-35). The conserved N-terminal region,
      however, remained essential for the antimicrobial activity of alarin as truncated
      peptides showed reduced killing effect. Moreover, alarin inhibited the growth of
      E. coli in a similar potency as human cathelicidin LL-37, a well-studied
      antimicrobial peptide. Electron microscopy further showed that alarin induced
      bacterial membrane blebbing but unlike LL-37, it did not cause hemolysis of
      erythrocytes. In addition, alarin is only active against the gram-negative
      bacteria, E. coli but not the gram-positive bacteria, Staphylococcus aureus.
      Thus, these data suggest that alarin has potentials as an antimicrobial and
      should be considered for the development in human therapeutics.

PMID- 23537645
TI  - Immunization with FSHbeta fusion protein antigen prevents bone loss in a rat
      ovariectomy-induced osteoporosis model.
AB  - Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally.
      Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT),
      is used widely in the clinic because it has been generally accepted that
      postmenopausal osteoporosis is caused by estrogen deficiency. However,
      hypogonadal alpha and beta estrogen receptor null mice were only mildly
      osteopenic, and mice with either receptor deleted had normal bone mass,
      indicating that estrogen may not be the only mediator that induces osteoporosis.
      Recently, follicle-stimulating hormone (FSH), the serum concentration of which
      increases from the very beginning of menopause, has been found to play a key role
      in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article,
      we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro
      and that this effect can be neutralized by either an anti-FSH monoclonal antibody
      or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST
      FSHbeta fusion protein antigen. Moreover, immunizing ovariectomized rats with the
      GST-FSHbeta antigen does significantly prevent trabecular bone loss and thereby
      enhance the bone strength, indicating that a FSH-based vaccine may be a promising
      therapeutic strategy to slow down bone loss in postmenopausal women.

PMID- 23537646
TI  - Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to
      oxidative stress-related endothelial dysfunction induced by angiotensin II in
      mice.
AB  - N-type voltage-dependent Ca(2+)channels (VDCCs), expressed predominantly in the
      nervous system, play pivotal roles in sympathetic regulation of the circulatory
      system. Although N-type VDCCs are also reportedly expressed in the vasculature,
      their pathophysiological role is obscure. We demonstrated that oxidative stress
      related endothelial dysfunction induced by angiotensin (Ang) II is suppressed in
      mice lacking the N-type VDCC alpha1B subunit (Cav 2.2). Impairment of endothelium
      dependent relaxation of the thoracic aorta observed following Ang II treatment in
      wild-type (WT) mice was significantly attenuated in the Ang II-treated Cav 2.2
      deficient mice, despite the comparable increase of the blood pressure in the two
      groups of mice. The thoracic aorta of the Cav 2.2-deficient mice showed a smaller
      positive area of oxidative stress markers as compared to the WT mice. The Ang II
      induced endothelial dysfunction was also suppressed by cilnidipine, an L/N-type
      VDCC blocker, but not by amlodipine, an L-type VDCC blocker; however, this unique
      effect of cilnidipine was completely abolished in the Cav 2.2-deficient mice.
      Furthermore, selective inhibition of N-type VDCCs by omega-conotoxin GVIA
      dramatically suppressed the production of reactive oxygen species (ROS) as well
      as agonist-induced Ca(2+) influx in the vascular endothelial cells. These results
      suggest that N-type VDCCs expressed in the vascular endothelial cells contribute
      to ROS production and endothelial dysfunction observed in Ang II-treated
      hypertensive mice.

PMID- 23537647
TI  - The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1
      to promote the proliferation of breast cancer cells.
AB  - We have reported that the oncoprotein hepatitis B virus X-interacting protein
      (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and
      migration of breast cancer cells. Previously, we showed that HBXIP was able to
      activate nuclear factor-kappaB (NF-kappaB) in breast cancer cells. As an
      oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays
      crucial roles in carcinogenesis. In the present study, we found that both HBXIP
      and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP
      was able to increase transcriptional activity of NF-kappaB through PDGFB,
      suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was
      able to upregulate PDGFB at the levels of mRNA, protein and promoter in the
      cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through
      activating transcription factor Sp1. In function, HBXIP enhanced the
      proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude
      that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote
      proliferation of breast cancer cells.

PMID- 23537648
TI  - Interaction of the S100A6 mutant (C3S) with the V domain of the receptor for
      advanced glycation end products (RAGE).
AB  - S100A6 is involved in several vital biological functions, such as calcium sensing
      and cell proliferation. It is a homodimeric protein that belongs to the S100
      protein family. The receptor for advanced glycation end products (RAGE) has been
      shown to play a role in the progression of various disease conditions, such as
      diabetes and immune/inflammatory disorders. Information regarding the association
      of RAGE with S100 proteins at a molecular level is useful to understand the
      diversity of the RAGE signaling pathways. In this report, biomolecular NMR
      techniques were utilized for the resonance assignment of the C3S mutation in
      human S100A6 and characterizing its interaction with the RAGE V domain. Further
      binding affinity between S100A6m and the RAGE V domain was determined by
      isothermal titration calorimetric studies. HADDOCK was used to generate a
      heterotetramer model of the S100A6m-RAGE V domain complex. This model provides an
      important insights into the S100-RAGE cellular signaling pathway.

PMID- 23537649
TI  - Estrogen-induced cell signaling in the sexually dimorphic nucleus of the rat
      preoptic area: potential involvement of cofilin in actin dynamics for cell
      migration.
AB  - Estrogen is a key factor to induce the sexually dimorphic nucleus (SDN) in the
      preoptic area (POA) of the rat brain. Identification of estrogen-dependent
      signaling pathways at SDN in POA during the critical period is a prerequisite for
      elucidating the mechanism. In the present study, we treated female rats
      with/without 17beta-estradiol (E2) at birth, designated as postnatal day 1 (P1),
      and prepared total RNA from brain slices containing SDN for DNA microarray
      analysis. Among the estrogen-responsive genes identified, protein kinase C-delta
      (PKC-delta) was significantly up-regulated by E2 at P5. We examined the
      downstream effectors of PKC-delta protein by Western blotting and found an E2
      induced PKC-delta/Rac1/PAK1/LIMK1/cofilin pathway. In the pathway, E2 suppressed
      the phosphorylation (inactive form) of cofilin. This result was supported by
      immunohistochemistry, where the phosphorylation/dephosphorylation of cofilin
      occurred at SDN, which suggests that cell migration is a cue to create sexual
      dimorphism in POA.

PMID- 23537650
TI  - Electron microscopic visualization of autophagosomes induced by infection of
      human papillomavirus pseudovirions.
AB  - Autophagy is a bulk degradation process for subcellular proteins and organelles
      to manage cell starvation. Autophagy is associated with the formation of
      autophagosomes and further functions as a defense mechanism against infection by
      various pathogens. Human papillomavirus (HPV) infection induces an autophagy
      response, such as up-regulation of marker proteins for autophagy, in host
      keratinocytes. However, direct microscopic evidence for autophagy induction by
      HPV infection is still lacking. Here, I report an electron microscopic analysis
      of autophagosomes elicited by the entry of HPV pseudovirions (PsVs). HeLa cells
      showed enhanced infectivity for PsVs of HPV type 16 (16PsVs) when treated with an
      autophagy inhibitor, suggesting the involvement of autophagy in HPV infection. In
      HeLa cells inoculated with 16PsVs, transmission electron microscopy showed the
      presence of cup-shaped, double-membrane vesicles (phagophores) and double
      membrane-bound vesicles, which are typical structures of autophagosomes. These
      double-membrane vesicles displayed a large lumen volume and incorporated 10-50
      16PsVs particles in the lumen. These results demonstrate that autophagy is indeed
      induced during the HPV16 entry process and imply that autophagosomes are
      generated from the plasma membrane by HPV infection.

PMID- 23537651
TI  - Association between MIF gene polymorphisms and carotid artery atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disorder. Macrophage migration
      inhibitory factor (MIF) is a potent cytokine that plays an important role in the
      regulation of immune responses. Polymorphisms including five- to eight-repeat
      CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are
      associated with altered levels of MIF gene transcription. The purpose of the
      study is to investigate the relationship between promoter polymorphisms of the
      MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity
      of CAA was assessed in 593 individuals with a history of ischemic stroke by using
      sonographic examination, and the MIF promoter polymorphisms of these individuals
      were genotyped. The carriage of (CATT)7 (compared to genotypes composed of
      (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage
      of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6
      G, or both) were significantly associated with an increase in the severity of
      CAA. We conclude that polymorphisms in the MIF gene promoter are associated with
      CAA severity in ischemic stroke patients. These genetic variants may serve as
      markers for individual susceptibility to CAA.

PMID- 23537652
TI  - Naphthazarin protects against glutamate-induced neuronal death via activation of
      the Nrf2/ARE pathway.
AB  - Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE)
      pathway is an important cellular stress response pathway involved in
      neuroprotection. We previously screened several natural phytochemicals and
      identified plumbagin as a novel activator of the Nrf2/ARE pathway that can
      protect neurons against ischemic injury. Here we extended our studies to natural
      and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4
      naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up
      regulates the expression of Nrf2-driven genes in primary neuronal and glial
      cultures, and protects neurons against glutamate-induced excitotoxicity.

PMID- 23537653
TI  - Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty
      liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic
      liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this
      study was to determine whether autophagy plays a role in the pathogenesis of
      NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon
      exposure to free fatty acids, as confirmed by the increase in the number of
      autophagosomes. However, exposure of hepatoma cells to H2O2 and TNF-alpha, two
      typical "second hit" factors, increased the initiation of autophagy but inhibited
      the autophagic flux. The inhibition of autophagy sensitized cells to pro
      apoptotic stimuli. Taken together, our results suggest that autophagy acts as a
      protective mechanism in the pathogenesis of NAFLD and that impairment of
      autophagy might induce more severe lesions of the liver. These findings will be a
      benefit to the understanding of the pathogenesis of NAFLD and might suggest a
      strategy for the prevention and cure of NAFLD.

PMID- 23537655
TI  - Quantum dot coating of baculoviral vectors enables visualization of transduced
      cells and tissues.
AB  - Imaging of transduced cells and tissues is valuable in developing gene transfer
      vectors and evaluating gene therapy efficacy. We report here a simple method to
      use bright and photostable quantum dots to label baculovirus, an emerging gene
      therapy vector. The labeling was achieved through the non-covalent interaction of
      glutathione-capped CdTe quantum dots with the virus envelope, without the use of
      chemical conjugation. The quantum dot labeling was nondestructive to viral
      transduction function and enabled the identification of baculoviral vector
      transduced, living cells based on red fluorescence. When the labeled baculoviral
      vectors were injected intravenously or intraventricularly for in vivo delivery of
      a transgene into mice, quantum dot fluorescence signals allow us monitor whether
      or not the injected tissues were transduced. More importantly, using a dual-color
      whole-body imaging technology, we demonstrated that in vivo viral transduction
      could be evaluated in a real-time manner in living mice. Thus, our method of
      labeling a read-to-use gene delivery vector with quantum dots could be useful
      towards the improvement of vector design and will have the potential to assess
      baculovirus-based gene therapy protocols in future.

PMID- 23537654
TI  - Nampt expression increases during osteogenic differentiation of multi- and
      omnipotent progenitors.
AB  - Despite emerging data showing that metabolic changes occur with stem cell
      differentiation, the cross-talk between factors governing energy metabolism and
      epigenetic modification is not understood. Nicotinamide adenine dinucleotide
      (NAD) participates in both energy metabolism and protein modification processes.
      Changes of the intracellular NAD concentration have been shown to correlate with
      differentiation of adult and embryonic stem cells. In the present study, we
      investigated the expression pattern of Nampt, the rate-limiting enzyme in NAD
      salvaging pathway, during osteogenic differentiation of the multipotent mouse
      fibroblast C3H10T1/2 and the omnipotent preosteoblast MC3T3-E1 cells. We found
      that Nampt was increasingly expressed during differentiation in both cell models.
      The increase of Nampt was associated with higher NAD concentration and Sirt1
      activity. Knockdown of Nampt or addition of its specific inhibitor FK866 leads to
      lower intracellular NAD concentration and decline in osteogenesis. These findings
      indicate that osteogenic differentiation correlates with intracellular NAD
      metabolism in which Nampt plays a regulatory role.

PMID- 23537656
TI  - HDL inhibits endoplasmic reticulum stress by stimulating apoE and CETP secretion
      from lipid-loaded macrophages.
AB  - The role of HDL in the modulation of endoplasmic reticulum (ER) stress in
      macrophage-derived foam cells is not completely understood. Therefore, we aimed
      to investigate whether HDL may inhibit ER stress in correlation with the
      secretion of apoE and CETP from lipid-loaded macrophages. To this purpose, THP-1
      macrophages were loaded with lipids by incubation with human oxidized LDL (oxLDL)
      and then exposed to human HDL3. ER stress signaling markers, protein kinase/Jun
      amino-terminal kinase (SAPK/JNK p54/p46) and eukaryotic initiation factor-2alpha
      (eIF2alpha), as well as the secreted apoE and CETP, were evaluated by immunoblot
      analysis. Out of the many different bioactive lipids of oxLDL, we tested the
      effect of 9-hydroxy-octadecadienoic acid (9-HODE) and 4-hydroxynonenal (4-HNE) on
      ER stress. Tunicamycin was used as positive control for ER stress induction.
      Results showed that oxLDL, 9-HODE and 4-HNE induce ER stress in human macrophages
      by activation of eIF-2alpha and SAPK/JNK (p54/p46) signaling pathways. OxLDL
      stimulated apoE and CETP secretion, while tunicamycin determined a reduction of
      the secreted apoE and CETP, both in control and lipid-loaded macrophages. The
      addition of HDL3 to the culture medium of tunicamycin-treated cells induced: (i)
      the reduction of ER stress, expressed as decreased levels of eIF-2alpha and
      SAPK/JNK, and (ii) a partial recovery of the secreted apoE and CETP levels in
      lipid-loaded macrophages. These data suggest a new mechanism by which HDL3
      diminish ER stress and stimulate cholesterol efflux from lipid-loaded
      macrophages.

PMID- 23537657
TI  - Oxidative stress suppresses the cellular bioenergetic effect of the 3
      mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway.
AB  - Recent data show that lower concentrations of hydrogen sulfide (H2S), as well as
      endogenous, intramitochondrial production of H2S by the 3-mercaptopyruvate (3
      MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron
      donor and inorganic source of energy to support mitochondrial electron transport
      and ATP generation in mammalian cells by donating electrons to Complex II. The
      aim of our study was to investigate the role of oxidative stress on the activity
      of the 3-MP/3-MST/H2S pathway in vitro. Hydrogen peroxide (H2O2, 100-500 MUM)
      caused a concentration-dependent decrease in the activity of recombinant mouse 3
      MST enzyme. In mitochondria isolated from murine hepatoma cells, H2O2 (50-500
      MUM) caused a concentration-dependent decrease in production of H2S from 3-MP. In
      cultured murine hepatoma cells H2O2, (3-100 MUM), did not result in overall
      cytotoxicity, but caused a partial decrease in basal oxygen consumption and
      respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100-300
      nM) was completely abolished by pre-treatment of the cells with H2O2 (50 MUM).
      The current findings demonstrate that oxidative stress inhibits 3-MST activity
      and interferes with the positive bioenergetic role of the 3-MP/3-MST/H2S pathway.
      These findings may have implications for the pathophysiology of various
      conditions associated with increased oxidative stress, such as various forms of
      critical illness, cardiovascular diseases, diabetes or physiological aging.

PMID- 23537658
TI  - Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by
      hybrid-compound histone deacetylase inhibitor.
AB  - OBJECTIVES: Histone deacetylase (HDAC) inhibitors are new therapeutic agents,
      used to treat various types of malignant cancers. In the present study, we
      investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth
      of mouse myeloma cells. MATERIALS AND METHODS: Myeloma cells, HS-72, P3U1, and
      mouse normal cells were used in this study. Effect of HDAC inhibitors on cell
      viability was determined by WST-assay and trypan blue assay. Cell cycle was
      analyzed using flow cytometer. The expression of cell cycle regulatory and the
      apoptosis associated proteins were examined by Western blot analysis. Hoechst's
      staining was used to detect apoptotic cells. RESULTS: Our findings showed that Ky
      2 decreased the levels of HDACs, while it enhanced acetylation of histone H3.
      Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2
      had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase
      cell cycle arrest and accumulation of a sub-G1 phase population, while Western
      blotting analysis revealed that expressions of the cell cycle-associated proteins
      were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in
      myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to
      induce apoptosis in bcl-2 overexpressing myeloma cells. CONCLUSION: These
      findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and
      Bcl-2-inhibitable mechanism in myeloma cells.

PMID- 23537659
TI  - Thymoquinone protects cultured rat primary neurons against amyloid beta-induced
      neurotoxicity.
AB  - Thymoquinone (TQ) is the main constituent of the oil extracted from Nigella
      sativa seeds, which is known to be the active constituent responsible for many of
      the seed antioxidant and anti-inflammatory effects. The present study was
      designed to investigate whether TQ can protect against Alzheimer's amyloid-beta
      peptide (Abeta) induced neurotoxicity in rat primary neurons. Cultured
      hippocampal and cortical neurons were treated with Abeta1-42 and TQ
      simultaneously for 72 h. Treatment with TQ efficiently attenuated Abeta1-42
      induced neurotoxicity, as evidenced by improved cell viability. TQ also inhibited
      the mitochondrial membrane potential depolarization and reactive oxygen species
      generation caused by Abeta1-42. In addition, TQ restored synaptic vesicle
      recycling inhibition, partially reversed the loss of spontaneous firing activity,
      and inhibited Abeta1-42 aggregation in vitro. These beneficial effects may
      contribute to the protection against Abeta-induced neurotoxicity. In conclusion,
      our results suggested that TQ has neuroprotection potential against Abeta1-42 in
      rat hippocampal and cortical neurons and thus may be a promising candidate for
      Alzheimer disease treatment.

PMID- 23537660
TI  - Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic
      nerve.
AB  - Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively)
      at high concentrations inhibit action potential conduction, it remains to be
      unknown whether TRPA1 agonists have a similar action. The present study examined
      the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate
      (AITC), which differ in chemical structure from each other, on compound action
      potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap
      method. CA and AITC concentration-dependently reduced the peak amplitude of the
      CAP with the IC50 values of 1.2 and 1.5mM, respectively; these activities were
      resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1
      antagonist HC-030031. The CA and AITC actions were distinct in property; the
      latter but not former action was delayed in onset and partially reversible, and
      CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by
      hydroxy-alpha-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1
      channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and
      tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC50=0.38
      mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have
      an ability to inhibit nerve conduction without TRP activation, although their
      agonists are quite different in chemical structure from each other.

PMID- 23537661
TI  - Effects of lactational and/or in utero exposure to environmental contaminants on
      the glucocorticoid stress-response and DNA methylation of the glucocorticoid
      receptor promoter in male rats.
AB  - Perinatal events can reprogram the hypothalamo-pituitary-adrenal axis for the
      entire lifespan leading to abnormal glucocorticoid stress-response (GSR) in
      adulthood: a phenomenon reported to be mediated by changes in DNA methylation of
      the glucocorticoid receptor (GR) gene promoter. We examined whether in utero
      and/or lactational exposure to mixtures of environmental contaminants can also
      induce abnormal GSR during adulthood. The experiment included nine treatment
      groups. From gestation day (GD) 0 until postnatal day (PND) 20, dams were fed
      daily with a cookie laced with corn oil (control) or a chemical mixture (M)
      [polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury]
      at 0.5 or 1.0mg/kg/day (0.5M, and M). At birth, some control (C) and M litters
      were cross-fostered to create four groups with the following in utero/postnatal
      exposure: C/C, M/C, C/M, M/M. Other dams received 1.8ng/kg/day of a mixture of
      aryl hydrocarbon receptor (AhR) agonists (non-ortho PCBs, PC-dibenzodioxins and
      PC-dibenzofurans) without or with 0.5M (0.5MAhR). In adult male offspring the
      abundance of GR in treated groups was not different from the control, but the AhR
      and M groups were significantly different from each other with opposite effects
      in the hippocampus and liver. There was no change in DNA methylation of the GR
      promoter (exon-17 and -110). Abnormal GSRs were detected in the AhR, 0.5MAhR, CM,
      and MM groups. The literature associates abnormal GSR with metabolic and mental
      health impairments, thus these results support further investigation of the
      influence of developmental exposure to environmental contaminants and
      predisposition to stress-induced diseases.

PMID- 23537662
TI  - Comment on "potential carcinogenic hazards of non-regulated disinfection by
      products: Haloquinones, halo-cyclopentene and cyclohexene derivatives, N
      halamines, halonitriles, and heterocyclic amines (Bull et al., 2011. Toxicology
      286, 1-19)".

PMID- 23537663
TI  - An approach for integrating toxicogenomic data in risk assessment: the dibutyl
      phthalate case study.
AB  - An approach for evaluating and integrating genomic data in chemical risk
      assessment was developed based on the lessons learned from performing a case
      study for the chemical dibutyl phthalate. A case study prototype approach was
      first developed in accordance with EPA guidance and recommendations of the
      scientific community. Dibutyl phthalate (DBP) was selected for the case study
      exercise. The scoping phase of the dibutyl phthalate case study was conducted by
      considering the available DBP genomic data, taken together with the entire data
      set, for whether they could inform various risk assessment aspects, such as
      toxicodynamics, toxicokinetics, and dose-response. A description of weighing the
      available dibutyl phthalate data set for utility in risk assessment provides an
      example for considering genomic data for future chemical assessments. As a result
      of conducting the scoping process, two questions--Do the DBP toxicogenomic data
      inform 1) the mechanisms or modes of action?, and 2) the interspecies differences
      in toxicodynamics?--were selected to focus the case study exercise. Principles of
      the general approach include considering the genomics data in conjunction with
      all other data to determine their ability to inform the various qualitative
      and/or quantitative aspects of risk assessment, and evaluating the relationship
      between the available genomic and toxicity outcome data with respect to study
      comparability and phenotypic anchoring. Based on experience from the DBP case
      study, recommendations and a general approach for integrating genomic data in
      chemical assessment were developed to advance the broader effort to utilize 21st
      century data in risk assessment.

PMID- 23537664
TI  - Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high
      affinity and act as potent agonists at cannabinoid type-2 receptors.
AB  - K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids,
      including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated
      metabolites of JWH-018 and JWH-073 retain high affinity and activity at
      cannabinoid type-1 receptors (CB1Rs), potentially contributing to the enhanced
      toxicity of K2 compared to marijuana. Since the parent compounds also bind to
      cannabinoid type-2 receptors (CB2Rs), this study investigated the affinity and
      intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites
      at human CB2Rs (hCB2Rs). The affinity of cannabinoids for hCB2Rs was determined
      by competition binding studies employing CHO-hCB2 membranes. Intrinsic activity
      of compounds was assessed by G-protein activation and adenylyl cyclase (AC)
      inhibition in CHO-hCB2 cells. JWH-073, JWH-018 and several of their human
      metabolites exhibit nanomolar affinity and act as potent agonists at hCB2Rs.
      Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to
      CB2Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is
      equipotent in regulating AC-activity when compared to the parent molecule.
      Finally, when compared to CP-55,940 and Delta(9)-tetrahydrocannabinol (Delta(9)
      THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB2R
      occupancy to produce similar levels of AC-inhibition, indicating that these
      compounds may more efficiently couple CB2Rs to AC than the well characterized
      cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and
      several major human metabolites of these compounds exhibit high affinity and
      demonstrate distinctive signaling properties at CB2Rs. Therefore, future studies
      examining pharmacological and toxicological properties of synthetic cannabinoids
      present in K2 products should consider potential actions of these drugs at both
      CB1 and CB2Rs.

PMID- 23537665
TI  - Synergistic gene and drug tumor therapy using a chimeric peptide.
AB  - Co-delivery of gene and drug for synergistic therapy has provided a promising
      strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide
      (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and
      fabricated. As a drug carrier, the micelles self-assembled from the peptide
      exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH
      7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily
      mediate transfection of pGL-3 reporter plasmid with or without the existence of
      serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability
      of peptide/DNA complexes was investigated by confocal laser scanning microscopy
      (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor
      effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the
      peptide micelles to form micelleplexes during the self-assembly of the peptide.
      Cellular uptake and intracellular delivery of gene and drug were studied by CLSM
      and flow cytometry respectively. And p53 protein expression was determined via
      Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition
      effect were also studied. Results suggest that the co-delivery of gene and drug
      from peptide micelles resulted in effective cell growth inhibition in vitro and
      significant tumor growth restraining in vivo. The chimeric peptide-based gene and
      drug co-delivery system will find great potential for tumor therapy.

PMID- 23537667
TI  - Doxorubicin delivery to 3D multicellular spheroids and tumors based on boronic
      acid-rich chitosan nanoparticles.
AB  - Boronic acid-rich chitosan-poly(N-3-acrylamidophenylboronic acid) nanoparticles
      (CS-PAPBA NPs) with the tunable size were successfully prepared by polymerizing N
      3-acrylamidophenylboronic acid in the presence of chitosan in an aqueous
      solution. The CS-PAPBA NPs were then functionalized by a tumor-penetrating
      peptide iRGD and loading doxorubicin (DOX). The interaction between boronic acid
      groups of hydrophobic PAPBA and the amino groups of hydrophilic chitosan inside
      the nanoparticles was examined by solid-state NMR measurement. The size and
      morphology of nanoparticles were characterized by dynamic light scattering and
      electron microscopy. The cellular uptake, tumor penetration, biodistribution and
      antitumor activity of the nanoparticles were evaluated by using three-dimensional
      (3-D) multicellular spheroids (MCs) as the in vitro model and H22 tumor-bearing
      mice as the in vivo model. It was found that the iRGD-conjugated nanoparticles
      significantly improved the efficiency of DOX penetration in MCs, compared with
      free DOX and non-conjugated nanoparticles, resulting in the efficient cell
      killing in the MCs. In vivo antitumor activity examination indicated that iRGD
      conjugated CS-PAPBA nanoparticles promoted the accumulation of nanoparticles in
      tumor tissue and enhanced their penetration in tumor areas, both of which
      improved the efficiency of DOX-loaded nanoparticles in restraining tumor growth
      and prolonging the life time of H22 tumor-bearing mice.

PMID- 23537668
TI  - Quality: performance improvement, teamwork, information technology and protocols.
AB  - Using the Institute of Medicine framework that outlines the domains of quality,
      this article considers four key aspects of health care delivery which have the
      potential to significantly affect the quality of health care within the pediatric
      intensive care unit. The discussion covers: performance improvement and how
      existing methods for reporting, review, and analysis of medical error relate to
      patient care; team composition and workflow; and the impact of information
      technologies on clinical practice. Also considered is how protocol-driven and
      standardized practice affects both patients and the fiscal interests of the
      health care system.

PMID- 23537666
TI  - Mapping calcium phosphate activated gene networks as a strategy for targeted
      osteoinduction of human progenitors.
AB  - Although calcium phosphate-containing biomaterials are promising scaffolds for
      bone regenerative strategies, the osteoinductive capacity of such materials is
      poorly understood. In this study, we investigated whether endogenous mechanisms
      of in vivo calcium phosphate-driven, ectopic bone formation could be identified
      and used to induce enhanced differentiation in vitro of the same progenitor
      population. To accomplish this, human periosteum derived cells (hPDCs) were
      seeded on hydroxyapatite/collagen scaffolds (calcium phosphate rich matrix or
      CPRM), or on decalcified scaffolds (calcium phosphate depleted matrix or CPDM),
      followed by subcutaneous implantation in nude mice to trigger ectopic bone
      formation. In this system, osteoblast differentiation occurred in CPRM scaffolds,
      but not in CPDM scaffolds. Gene expression was assessed by human full-genome
      microarray at 20 h after seeding, and 2, 8 and 18 days after implantation. In
      both matrices, implantation of the cell constructs triggered a similar gene
      expression cascade, however, gene expression dynamics progressed faster in CPRM
      scaffolds than in CPDM scaffolds. The difference in gene expression dynamics was
      associated with differential activation of hub genes and molecular signaling
      pathways related to calcium signaling (CREB), inflammation (TNFalpha, NFkB, and
      IL6) and bone development (TGFbeta, beta-catenin, BMP, EGF, and ERK signaling).
      Starting from this set of pathways, a growth factor cocktail was developed that
      robustly enhanced osteogenesis in vitro and in vivo. Taken together, our data
      demonstrate that through the identification and subsequent stimulation of genes,
      proteins and signaling pathways associated with calcium phosphate mediated
      osteoinduction, a focused approach to develop targeted differentiation protocols
      in adult progenitor cells can be achieved.

PMID- 23537669
TI  - Pediatric status asthmaticus.
AB  - Status asthmaticus is a frequent cause of admission to a pediatric intensive care
      unit. Prompt assessment and aggressive treatment are critical. First-line or
      conventional treatment includes supplemental oxygen, aerosolized albuterol, and
      corticosteroids. There are several second-line treatments available; however, few
      comparative studies have been performed and in the absence of good evidence-based
      treatments, the use of these therapies is highly variable and dependent on local
      practice and provider preference. In this article the pathophysiology and
      treatment of status asthmaticus is discussed, and the literature regarding second
      line treatments is critically assessed to apply an evidence basis to the
      treatment of this severe disease.

PMID- 23537670
TI  - Acute respiratory failure.
AB  - Acute respiratory failure is common in critically ill children, who are at
      increased risk of respiratory embarrassment because of the developmental
      variations in the respiratory system. Although multiple etiologies exist,
      pneumonia and bronchiolitis are most common. Respiratory system monitoring has
      evolved, with the clinical examination remaining paramount. Invasive tests are
      commonly replaced with noninvasive monitors. Children with ALI/ARDS have better
      overall outcomes than adults, although data regarding specific therapies are
      still lacking. Most children will have some degree of long-term physiologic
      respiratory compromise after recovery from ALI/ARDS. The physiologic basis for
      respiratory failure and its therapeutic options are reviewed here.

PMID- 23537671
TI  - Pediatric postoperative cardiac care.
AB  - Postoperative care of cardiac patients requires a comprehensive and
      multidisciplinary approach to critically ill patients with cardiac disease whose
      care requires a clear understanding of cardiovascular physiology. When a patient
      fails to progress along the projected course or decompensates acutely, prompt
      evaluation with bedside assessment, laboratory evaluation, and echocardiography
      is essential. When things do not add up, cardiac catheterization must be
      seriously considered. With continued advancements in the field of neonatal and
      pediatric postoperative cardiac care, continued improvements in overall outcomes
      for this specialized population are anticipated.

PMID- 23537672
TI  - Pediatric sepsis: challenges and adjunctive therapies.
AB  - Sepsis remains an important challenge in pediatric critical care medicine. This
      review provides an appraisal of adjunctive therapies for sepsis and highlights
      opportunities for meeting selected challenges in the field. Future clinical
      studies should address long-term and functional outcomes as well as acute
      outcomes. Potential adjunctive therapies such as corticosteroids, hemofiltration,
      hemoadsorption, and plasmapheresis may have important roles, but still require
      formal and more rigorous testing by way of clinical trials. Finally, the design
      of future clinical trials should consider novel approaches for stratifying
      outcome risks as a means of improving the risk-to-benefit ratio of experimental
      therapies.

PMID- 23537673
TI  - Pediatric traumatic brain injury in 2012: the year with new guidelines and common
      data elements.
AB  - Traumatic brain injury (TBI) remains the leading cause of death of children in
      the developing world. In 2012, several international efforts were completed to
      aid clinicians and researchers in advancing the field of pediatric TBI. The
      second edition of the Guidelines for the Medical Management of Traumatic Brain
      Injury in Infants, Children and Adolescents updated those published in 2003. This
      article highlights the processes involved in developing the Guidelines, contrasts
      the new guidelines with the previous edition, and delineates new research efforts
      needed to advance knowledge. The impact of common data elements within these
      potential new research fields is reviewed.

PMID- 23537674
TI  - Pediatric intensive care treatment of uncontrolled status epilepticus.
AB  - The critically ill mechanically ventilated child with ongoing seizures that are
      refractory to any treatment presents a distinct challenge in pediatric
      neurocritical care. The evidence base from randomized controlled trials on which
      anti-epileptic drug (AED) strategy should be used is inadequate. This review of
      refractory and super-refractory status epilepticus summarizes recent pediatric
      case series regarding definitions, the second-tier AED therapies once initial
      anticonvulsants have failed, and the experience of high-dose midazolam,
      barbiturate anesthesia, and volatile anesthetics for uncontrolled status
      epilepticus.

PMID- 23537675
TI  - Acute encephalitis.
AB  - Acute encephalitis remains one of the contemporary challenges of critical care
      medicine. The diagnosis is difficult and sometimes unconfirmed, and encephalitis
      remains without clear evidence-based therapies or even therapeutic goals for the
      prevention of high neurologic sequelae. This article provides a framework for
      pediatric intensivists to guide the diagnosis and management of patients with
      suspected encephalitis. It provides an in-depth review of the most common causes
      of encephalitis in children. The article promotes early recognition, appropriate
      testing and empiric treatment, and management of the expected complications of
      acute encephalitis.

PMID- 23537676
TI  - Renal complications and therapy in the PICU: hypertension, CKD, AKI, and RRT.
AB  - This article provides the bedside clinician an overview of the unique renal
      complications that are seen commonly in the pediatric intensive care unit. These
      sections are purposely succinct to give a quick guide to the clinician for the
      care of these children. We have identified four major areas that should result in
      discussion and cooperative care between intensive care physicians and
      nephrologists for the care of these children: (1) hypertension, (2) chronic
      kidney failure, (3) acute kidney injury, and (4) renal replacement therapy.

PMID- 23537677
TI  - Anemia and transfusion in critically ill pediatric patients: a review of
      etiology, management, and outcomes.
AB  - This article describes the incidence and etiology of anemia in critically ill
      children. In addition, the article details the pathophysiology and clinical
      ramifications of anemia in this population. The use of transfused packed red
      blood cells as a therapy for anemia in critically ill patients is also discussed,
      including the indications for and complications associated with this practice as
      well as potential reasons for these complications. Finally, the article lists
      some therapeutic practices that may lessen the risks associated with transfusion,
      and briefly discusses the use of blood substitutes.

PMID- 23537678
TI  - Coagulopathies in the PICU: DIC and liver disease.
AB  - Bleeding in patients in pediatric intensive care units is associated with an
      increased risk of mortality. Fortunately, most patients with an abnormal
      coagulation profile do not bleed because this is generally secondary to liver
      disease or dietary-induced vitamin K deficiency. When the laboratory markers of
      coagulopathy are the result of disseminated intravascular coagulation, bleeding
      is common and the risk of mortality extreme. Although interventions directed
      toward correcting the abnormal coagulation test results are generally initiated,
      they are also generally either not warranted or not fully successful.

PMID- 23537679
TI  - Common endocrine issues in the pediatric intensive care unit.
AB  - Thyroid hormone is central to normal development and metabolism. Abnormalities in
      thyroid function in North America often arise from autoimmune diseases, but they
      rarely present as critical illness. Severe deficiency or excess of thyroid
      hormone both represent life-threatening disease, which must be treated
      expeditiously and thoroughly. Such deficiencies must be considered, because
      presentation may be nonspecific.

PMID- 23537680
TI  - Medical ethics in pediatric critical care.
AB  - Ethically charged situations are common in pediatric critical care. Most
      situations can be managed with minimal controversy within the medical team or
      between the team and patients/families. Familiarity with institutional resources,
      such as hospital ethics committees, and national guidelines, such as publications
      from the American Academy of Pediatrics, American Medical Association, or Society
      of Critical Care Medicine, are an essential part of the toolkit of any
      intensivist. Open discussion with colleagues and within the multidisciplinary
      team can also ensure that when difficult situations arise, they are addressed in
      a proactive, evidence-based, and collegial manner.

PMID- 23537681
TI  - Preface. 10 Common medical and surgical problems.

PMID- 23537682
TI  - Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO
      ANCA-associated glomerulonephritis.
AB  - Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)- associated
      glomerulonephritis (GN) is characterized by pauci-immune necrotizing
      glomerulonephritis(NGN). Although it has been thought that MPO-ANCA is involved
      in the pathogenesis of capillary injuries in NGN via activation of neutrophils,
      recent studies suggest a possible role of other factors such as immunoglobulins
      precipitated on the glomeruli. Here we performed a pathological study
      investigating a relationship of deposition of MPO, IgG, complements with regard
      to MPO-positive cells and glomerular capillaries in human MPO-ANCA-associated GN.
      Renal specimen including 317 glomeruli obtained from 20 patients with MPOANCA-
      associated GN were analyzed. All of the specimens showed significant focal
      segmental deposition of IgG. There was a significant glomerular infiltration of
      MPO-positive cells along with deposition of extracellular MPO in the active
      lesions of segmental and global NCG, with CD34 staining being decreased in the
      adjacent areas. IgG deposits were almost colocalized with C3 and partly with MPO,
      which are also associated with a decrease in CD34 staining, suggesting that
      immune complex formation and the resultant capillary injuries. Actually occurred,
      the colocalization of MPO, IgG and C3 was seen only in the glomerular lesions
      with low severity and activity. These results suggest that not only MPO itself
      released from the neutrophils but also immune complexes composed of MPO and anti
      MPO antibody may play some pathogenetic roles for the glomerular injuries
      especially in the early phase of human MPO-ANCA-associated GN.

PMID- 23537683
TI  - Pseudo-blood leak? A hemodialysis mystery.
AB  - Hydroxocobalamin is a treatment for cyanide toxicity with few side effects. We
      report a case of a hemodialysis patient whose treatment was compromised by
      hydroxocobalamin interference with the blood leak detector.

PMID- 23537684
TI  - Minimal change disease caused by exposure to mercury-containing skin lightening
      cream: a report of 4 cases.
AB  - Mercury is a known cause of nephrotic syndrome and the underlying renal pathology
      in most of the reported cases was membranous nephropathy. We describe here 4
      cases of minimal change disease following exposure to mercury-containing skin
      lightening cream for 2 - 6 months. The mercury content of the facial creams was
      very high (7,420 - 30,000 parts per million). All patients were female and
      presented with nephrotic syndrome and heavy proteinuria (8.35 - 20.69 g/d). The
      blood and urine mercury levels were 26 - 129 nmol/l and 316 - 2,521 nmol/d,
      respectively. Renal biopsy revealed minimal change disease (MCD) in all patients.
      The use of cosmetic cream was stopped and chelation therapy with D-penicillamine
      was given. Two patients were also given steroids. The time for blood mercury
      level to normalize was 1 - 7 months, whereas it took longer for urine mercury
      level to normalize (9 - 16 months). All patients had complete remission of
      proteinuria and the time to normalization of proteinuria was 1 - 9 months.
      Mercury-containing skin lightening cream is hazardous because skin absorption of
      mercury can cause minimal change disease. The public should be warned of the
      danger of using such products. In patients presenting with nephrotic syndrome, a
      detailed history should be taken, including the use of skin lightening cream.
      With regard to renal pathology, apart from membranous nephropathy, minimal change
      disease should be included as another pathological entity caused by mercury
      exposure or intoxication.

PMID- 23537685
TI  - What lies beneath: Fabry nephropathy in a female patient with severe
      cerebrovascular disease.
AB  - Fabry disease is an X-linked inborn error of metabolism, which is caused by the
      deficiency of &#945;-galactosidase A, leading to progressive accumulation of
      neutral glycosphingolipids and a-galactosyl breakdown products in most body
      fluids and several tissues, resulting in the clinical manifestations. The onset
      of Fabry disease symptoms in females is not observed as early as in males. We
      report a novel presentation of Fabry disease in a female patient with medical
      history of relapsing strokes and brain magnetic resonance angiography showing
      signs of microangiopathy and multiple lacunar strokes that were first diagnosed
      as Moyamoya disease (a chronic progressive cerebrovascular disease). The patient
      subsequently displayed increased levels of serum creatinine and proteinuria.
      Diagnosis of Fabry disease was made by a renal biopsy and was confirmed by
      molecular studies showing a missense mutation: c1066C > T (het) [R356W]. The
      diagnosis was delayed by 21 years with respect to her first symptom (stroke),
      probably because her initial clinical presentation was neurological and diagnosed
      as Moyamoya disease. Other factors that contributed to the delay of the diagnosis
      were the lack of acute or chronic pain (neuropathic pain) and angiokeratomas.
      Some similarities in the pathogenic aspects of the patient's vascular lesions
      lead us to speculate that this patient has Fabry disease, with a phenotype that
      had not yet been described. It is necessary to be aware of this possibility to
      avoid misdiagnosis of Fabry disease as Moyamoya disease.

PMID- 23537686
TI  - Standards of reporting for MRI-targeted biopsy studies (START) of the prostate:
      recommendations from an International Working Group.
AB  - BACKGROUND: A systematic literature review of magnetic resonance imaging (MRI)
      targeted prostate biopsy demonstrates poor adherence to the Standards for the
      Reporting of Diagnostic Accuracy (STARD) recommendations for the full and
      transparent reporting of diagnostic studies. OBJECTIVE: To define and recommend
      Standards of Reporting for MRI-targeted Biopsy Studies (START). DESIGN, SETTING,
      AND PARTICIPANTS: Each member of a panel of 23 experts in urology, radiology,
      histopathology, and methodology used the RAND/UCLA appropriateness methodology to
      score a 258-statement premeeting questionnaire. The collated responses were
      presented at a face-to-face meeting, and each statement was rescored after group
      discussion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Measures of agreement
      and consensus were calculated for each statement. The most important statements,
      based on group median score, the degree of group consensus, and the content of
      the group discussion, were used to create a checklist of reporting criteria (the
      START checklist). RESULTS AND LIMITATIONS: The strongest recommendations were to
      report histologic results of standard and targeted cores separately using Gleason
      score and maximum cancer core length. A table comparing detection rates of
      clinically significant and clinically insignificant disease by targeted and
      standard approaches should also be used. It was recommended to report the
      recruitment criteria for MRI-targeted biopsy, prior biopsy status of the
      population, a brief description of the MRI sequences, MRI reporting method,
      radiologist experience, and image registration technique. There was uncertainty
      about which histologic criteria constitute clinically significant cancer when the
      prostate is sampled using MRI-targeted biopsy, and it was agreed that a new
      definition of clinical significance in this setting needed to be derived in
      future studies. CONCLUSIONS: Use of the START checklist would improve the quality
      of reporting in MRI-targeted biopsy studies and facilitate a comparison between
      standard and MRI-targeted approaches.

PMID- 23537687
TI  - Efficacy and safety of solifenacin plus tamsulosin OCAS in men with voiding and
      storage lower urinary tract symptoms: results from a phase 2, dose-finding study
      (SATURN).
AB  - BACKGROUND: Storage symptoms are often undertreated in men with lower urinary
      tract symptoms (LUTS). OBJECTIVE: To evaluate the combination of an
      antimuscarinic (solifenacin) with an alpha-blocker (tamsulosin) versus tamsulosin
      alone in the treatment of men with LUTS. DESIGN, SETTING, AND PARTICIPANTS: A
      double-blind, 12-wk, phase 2 study in 937 men with LUTS (>= 3 mo, total
      International Prostate Symptom Score [IPSS] >= 13, and maximum urinary flow rate
      4.0-15.0 ml/s). INTERVENTION: Eight treatment groups: tamsulosin oral controlled
      absorption system (OCAS) 0.4 mg; solifenacin 3, 6, or 9 mg; solifenacin 3, 6 or 9
      mg plus tamsulosin OCAS 0.4 mg; or placebo. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The primary efficacy end point was change from baseline in total IPSS.
      Secondary end points included micturition diary and quality-of-life (QoL)
      parameters. Post hoc subgroup analyses were performed by severity of baseline
      storage symptoms, with statistical comparisons presented only for tamsulosin OCAS
      alone versus combination therapy, due to the small sample size of the solifenacin
      monotherapy and placebo subgroups. RESULTS AND LIMITATIONS: Combination therapy
      was associated with significant improvements in micturition frequency and voided
      volume versus tamsulosin OCAS alone in the total study population; improvements
      in total IPSS were not significant. Statistically significant improvements in
      urgency episodes, micturition frequency, total urgency score, voided volume, IPSS
      storage subscore, IPSS-QoL index, and Patient Perception of Bladder Condition
      were observed in a subpopulation of men with two or more urgency episodes per 24h
      (Patient Perception of Intensity of Urgency Scale grade 3 or 4) and eight or more
      micturitions per 24h at baseline (storage symptoms subgroup) with combination
      therapy versus tamsulosin OCAS alone (p <= 0.05 for the dose-response slope, all
      variables). Combination therapy was well tolerated, and adverse events were
      consistent with the safety profiles of both compounds. CONCLUSIONS: Solifenacin
      plus tamsulosin OCAS did not significantly improve IPSS in the total study
      population but offered significant efficacy and QoL benefits over tamsulosin OCAS
      monotherapy in men with both voiding and storage symptoms at baseline.
      Combination therapy was well tolerated. TRIAL REGISTRATION: Clinical Trials.gov
      Identifier: NCT00510406.

PMID- 23537688
TI  - Animal biometrics: quantifying and detecting phenotypic appearance.
AB  - Animal biometrics is an emerging field that develops quantified approaches for
      representing and detecting the phenotypic appearance of species, individuals,
      behaviors, and morphological traits. It operates at the intersection between
      pattern recognition, ecology, and information sciences, producing computerized
      systems for phenotypic measurement and interpretation. Animal biometrics can
      benefit a wide range of disciplines, including biogeography, population ecology,
      and behavioral research. Currently, real-world applications are gaining momentum,
      augmenting the quantity and quality of ecological data collection and processing.
      However, to advance animal biometrics will require integration of methodologies
      among the scientific disciplines involved. Such efforts will be worthwhile
      because the great potential of this approach rests with the formal abstraction of
      phenomics, to create tractable interfaces between different organizational levels
      of life. 

PMID- 23537689
TI  - Can positive frequency dependence facilitate plant coexistence?

PMID- 23537690
TI  - Ecological character displacement: glass half full or half empty?
AB  - Ecological character displacement (ECD), the evolutionary divergence of competing
      species, has oscillated wildly in scientific opinion. Initially thought to play a
      central role in community assembly and adaptive radiation, ECD recovered from a
      1980s nadir to present-day prominence on the strength of many case studies
      compiled in several influential reviews. However, we reviewed recent studies and
      found that only nine of 144 cases are strong examples that have ruled out
      alternative explanations for an ECD-like pattern. We suggest that the rise in
      esteem of ECD has outpaced available data and that more complete, rather than
      simply more, case studies are needed. Recent years have revealed that
      evolutionary change can be observed as it occurs, opening the door to
      experimental field studies as a new approach to studying ECD. 

PMID- 23537691
TI  - Spatial variation and subcellular binding of metals in oysters from a large
      estuary in China.
AB  - Pearl River Estuary (PRE) is the largest estuary in Southern China and there has
      been an increasing concern of metal pollution due to regional industrialization.
      In this study, we investigated the spatial variation of metal pollution (Ag, As,
      Cd, Cu, Pb, and Zn) as well as their subcellular handling in the oyster
      Crassostrea hongkongensis. Hot spots of metal contamination in the oysters were
      found in different sites, suggesting that there were different sources of metals
      in the estuary associated with industrial activity. Metals differed in their
      subcellular bindings in the oysters from different locations. Metal distribution
      in the biologically detoxified fraction decreased for Cu but increased for Zn
      with increasing contamination in the oysters. For Zn, there was a significant
      difference in its two detoxification pools (metal-rich granules and
      metallothionein-like proteins) in response to Zn contamination. The high Cd
      concentrations in oysters may carry a high Cd hazard to the consumers.

PMID- 23537692
TI  - Subcellular localization of the fatty acyl reductase involved in pheromone
      biosynthesis in the tobacco budworm, Heliothis virescens (Noctuidae:
      Lepidoptera).
AB  - Sex pheromone components are produced in specialized glands of female moths via
      well-characterized biosynthetic pathways, where a Fatty Acyl Reductase (FAR) is
      often essential for producing the specific ratio of the different pheromone
      components. The subcellular localization and membrane topology of FARs is
      important for understanding how pheromones are synthesized and exported to the
      exterior for release. We investigated the subcellular localization of HvFAR from
      the noctuid moth Heliothis virescens by producing recombinant fusion proteins
      with green fluorescent protein (GFP) in yeast. A C-terminally tagged construct
      was localized to the endoplasmic reticulum (ER) and retained full reductive
      activity on a broad range of saturated and unsaturated fatty acyl precursors. In
      contrast, an N-terminally-tagged construct was poorly expressed in the cytoplasm
      and was not enzymatically active, indicating that HvFAR requires a free N
      terminal for both proper targeting and catalytic activity. A series of
      truncations of the N-and C-termini of HvFAR was conducted based on in silico
      predicted hydrophobic domains and transmembrane regions. The N-terminally
      truncated protein was found in the cytoplasm and did not retain activity,
      emphasizing the importance of the N-terminal for FAR function. In addition, the
      orientation in the membrane of the C-terminus-tagged HvFAR-GFP construct was
      analyzed using a fluorescence protease protection (FPP) assay, implying that the
      C-terminal of HvFAR is orientated towards the cytoplasm. These results, together
      with previous data on the localization of desaturases, confirm the importance of
      the ER as a subcellular site of pheromone production.

PMID- 23537693
TI  - A consensus process on the use of exercises and after action reports to assess
      and improve public health emergency preparedness and response.
AB  - INTRODUCTION: The objective of disaster preparedness is to ensure that
      appropriate systems, procedures, and resources are in place to provide prompt,
      effective assistance to disaster victims, thus facilitating relief measures and
      rehabilitation of services. Disaster preparedness efforts include the
      identification of possible health scenarios based on the probability of hazards
      and vulnerability of the population as a basis for creating a disaster plan.
      Exercises that simulate emergency response, involving the health and other
      sectors, have been suggested as useful tools to test the plans on a regular basis
      and measure preparedness efforts; the absence of actual testing is likely to
      negate even the best of abstract plans. Problem Exercises and after action
      reports (AARs) are used to document preparedness activities. However, to date,
      limited analysis has been performed on what makes an exercise an effective tool
      to assess public health emergency preparedness (PHEP), and how AARs can be
      developed and used to support PHEP improvement efforts. The scope of this project
      was to achieve consensus on: (1) what makes an exercise an effective tool to
      assess PHEP; and (2) what makes an AAR an effective tool to guide PHEP
      improvement efforts. METHODS: Sixty-one PHEP experts were convened by the use of
      Nominal Group Techniques to achieve consensus on a series of characteristics that
      exercises should have when designed to assess PHEP and on the recommendations for
      developing high-quality AARs. RESULTS: The panelists achieved consensus on a list
      of recommendations to improve the use of exercises and AARs in PHEP improvement
      efforts. Such recommendations ranged from the characteristics of the exercise
      audience to the evaluation methodology being used and the characteristics of the
      produced AAR such as its structure and content. CONCLUSIONS: The characteristics
      of the exercise audience, scenario and scope are among the most important
      attributes to the effectiveness of an exercise conducted for PHEP evaluation
      purposes. The evaluation instruments used to gather observations need an
      appropriate matching between exercise objectives and the response capabilities
      tested during the exercise, to build the base for the production of a good AAR.
      Improvements in the design and creation of exercises and AARs could facilitate
      better reporting and measurement of preparedness outcomes.

PMID- 23537694
TI  - Liquid chromatography-tandem mass spectrometric assay for the mutated BRAF
      inhibitor dabrafenib in mouse plasma.
AB  - A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC
      MS/MS) assay for the mutated BRAF inhibitor dabrafenib was developed and
      validated. Plasma samples were pre-treated using protein precipitation with
      acetonitrile containing PLX4720 as internal standard. The extract was directly
      injected into the reversed-phase chromatographic system after dilution with
      water. The eluate was transferred into the electrospray interface with positive
      ionization and the analyte was detected in the selected reaction monitoring mode
      of a triple quadrupole mass spectrometer. The assay was validated in a 2-2000
      ng/ml calibration range with r(2)=0.993+/-0.002 for linear regression with
      quadratic weighting (n=5). Within day precisions (n=6) were 3.3-5.2%, between day
      (3 days; n=18) precisions 4.7-8.2%. Accuracies were between 95-104% for the whole
      calibration range. The drug was sufficiently stable under all relevant analytical
      conditions. Finally, the assay was successfully used to determine drug
      pharmacokinetics in mice.

PMID- 23537695
TI  - Fibular taping does not influence ankle dorsiflexion range of motion or balance
      measures in individuals with chronic ankle instability.
AB  - OBJECTIVES: To determine the effects of fibular taping on ankle dorsiflexion
      range of motion (ROM) and dynamic balance in individuals with chronic ankle
      instability (CAI). DESIGN: Single-blind, randomized crossover. METHODS: Twenty
      three individuals (age=23.4 +/- 2.5 years, height=171.6 +/- 12.4 cm, mass=71.5+/
      13.1 kg) with CAI were allocated to either a fibular taping intervention or sham
      taping intervention (tape applied without tension) over the course of two visits.
      Weight-bearing ankle dorsiflexion ROM and components of the Star Excursion
      Balance Test (SEBT) were measured before and after intervention. RESULTS: There
      was not a significant change in ankle dorsiflexion ROM when comparing the taping
      interventions (F1,43=1.03, P=.32), but both interventions resulted in a small
      increase (F1,43=8.07, P=.007) in dorsiflexion ROM (pre=36.7 degrees  +/- 6.9
      degrees , post=37.7 degrees  +/- 6.2 degrees ). This increase in ROM did not
      exceed the established minimal detectable change for dorsiflexion ROM. Fibular
      taping with tension produced an increase (F1,41=5.84, P=.02) (pre=69.0 +/- 9.1%,
      post=70.6+/-8.6%) in posterolateral reach distance when compared to taping
      without tension (pre=72.7 +/- 11.0%, post=71.4 +/- 9.6%), but this increase did
      not exceed the established minimal detectable change. There was not a significant
      change in dynamic balance between groups for the anterior (F1,41=2.33, P=.14) and
      posteromedial (F1,41=.41, P=.53) reach directions. CONCLUSIONS: Although small
      changes in ankle dorsiflexion ROM and posterolateral reach distances were
      observed, these changes did not exceed established minimal detectable change
      values for these measures. These results suggest that the benefits of fibular
      taping are not related to an increase in ankle dorsiflexion ROM or dynamic
      balance.

PMID- 23537696
TI  - Clinical practice guidelines for the perioperative nutritional, metabolic, and
      nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by
      American Association of Clinical Endocrinologists, the Obesity Society, and
      American Society for Metabolic & Bariatric Surgery.
AB  - The development of these updated guidelines was commissioned by the AACE, TOS,
      and ASMBS Board of Directors and adheres to the AACE 2010 protocol for
      standardized production of clinical practice guidelines (CPG). Each
      recommendation was re-evaluated and updated based on the evidence and subjective
      factors per protocol. Examples of expanded topics in this update include: the
      roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes,
      bariatric surgery for patients with mild obesity, copper deficiency, informed
      consent, and behavioral issues. There are 74 recommendations (of which 56 are
      revised and 2 are new) in this 2013 update, compared with 164 original
      recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1,
      131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a
      relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with
      only 16.5% in the 2008 AACE-TOS-ASMBS CPG. These updated guidelines reflect
      recent additions to the evidence base. Bariatric surgery remains a safe and
      effective intervention for select patients with obesity. A team approach to
      perioperative care is mandatory with special attention to nutritional and
      metabolic issues.

PMID- 23537698
TI  - Rapid induction of mild therapeutic hypothermia by extracorporeal veno-venous
      blood cooling in humans.
AB  - AIM: Mild therapeutic hypothermia is beneficial in patients successfully
      resuscitated from non-traumatic out-of-hospital cardiac arrest. The effect of
      fast induction of hypothermia in these patients remains to be investigated. The
      aim of this study was to evaluate the efficacy and safety of extracorporeal veno
      venous blood cooling in humans successfully resuscitated from cardiac arrest.
      METHODS: We performed an interventional study in patients after successful
      resuscitation from cardiac arrest admitted to the emergency department of a
      tertiary care centre. The extracorporeal veno-venous circulation was established
      via a percutaneously introduced double lumen dialysis catheter in the femoral
      vein, and a tubing circuit and heat exchanger. A paediatric cardiopulmonary
      bypass roller pump and a heater-cooler system were used to circulate the blood.
      Main outcome measures were feasibility, efficacy, and safety. RESULTS: We
      included eight consecutive cardiac arrest patients with a median oesophageal
      temperature of 35.9 degrees C (interquartile range 34.9-37.0). A median time of 8
      min elapsed (interquartile range 5-15 min) to reach oesophageal temperatures
      below 34 degrees C, which reflects a cooling rate of 12.2 degrees C/h
      (interquartile range 10.8 degrees C/h to 14.1 degrees C/h). The predefined target
      temperature of 33.0 degrees C was reached after 14 min (interquartile range 8-21
      min). No device or method related adverse events were reported. CONCLUSION:
      Extracorporeal veno-venous blood cooling is a feasible, safe, and very fast
      approach for induction of mild therapeutic hypothermia in patients successfully
      resuscitated from cardiac arrest.

PMID- 23537699
TI  - SBAR improves nurse-physician communication and reduces unexpected death: a pre
      and post intervention study.
AB  - BACKGROUND: The Joint Commission International Patient Safety Goal 2 states that
      effective communication between health care workers needs to improve. The aim of
      this study was to determine the effect of SBAR (situation, background,
      assessment, recommendation) on the incidence of serious adverse events (SAE's) in
      hospital wards. METHOD: In 16 hospital wards nurses were trained to use SBAR to
      communicate with physicians in cases of deteriorating patients. A pre (July 2010
      and April 2011) and post (June 2011 and March 2012) intervention study was
      performed. Patient records were checked for SBAR items up to 48 h before a SAE. A
      questionnaire was used to measure nurse-physician communication and
      collaboration. RESULTS: During 37,239 admissions 207 SAE's occurred and were
      checked for SBAR items, 425 nurses were questioned. Post intervention all four
      SBAR elements were notated more frequently in patient records in case of a SAE
      (from 4% to 35%; p<0.001), total score on the questionnaire increased in nurses
      (from 58 (range 31-97) to 64 (range 25-97); p<0.001), the number of unplanned
      intensive care unit (ICU) admissions increased (from 13.1/1000 to 14.8/1000
      admissions; relative risk ratio (RRR)=50%; 95% CI 30-64; p=0.001) and unexpected
      deaths decreased (from 0.99/1000 to 0.34/1000 admissions; RRR=-227%; 95% CI -793
      to -20; NNT 1656; p<0.001). There was no difference in the number of cardiac
      arrest team calls. CONCLUSION: After introducing SBAR we found increased
      perception of effective communication and collaboration in nurses, an increase in
      unplanned ICU admissions and a decrease in unexpected deaths.

PMID- 23537700
TI  - Similar pyruvate kinase modifications in glioblastoma cells by 7beta
      hydroxycholesterol and glutamine withdrawal.
AB  - Oxysterols possess anti-proliferative properties that may be used with much
      effect in the treatment of cancer. We have demonstrated previously that 7 beta
      hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK
      activation, and changes in lipid raft composition in C6 glioblastoma cells. These
      observations suggested that glycolysis might have been changed. Here we will show
      that 7b-HC increases cell cycle time and that it changes the affinity of pyruvate
      kinase to its substrate, phosphoenol pyruvate. The latter effect is mimicked by
      glutamine withdrawal.

PMID- 23537702
TI  - Systematic evaluation of 640 FDA drugs for their effect on CD4+Foxp3+ regulatory
      T cells using a novel cell-based high throughput screening assay.
AB  - Regulatory T cells (Treg), which play a pivotal role in maintaining immune
      homeostasis by suppressing the proliferation of effector T cells, have great
      therapeutic potential for autoimmune diseases and transplantation. However,
      progress on their clinical application has been hampered by the lack of high
      throughput screening (HTS) strategies for the systematic and rapid evaluation of
      existing drugs and the identification of novel drug candidates. In this report,
      we present an innovative in vitro HTS assay using CD4+ T cells from Foxp3-GFP
      transgenic mice that specifically express the GFP signal in Foxp3+ Treg cells
      detectable by FACS analysis in a high throughput manner. Systematic evaluation of
      640 FDA-approved drugs revealed that 70 drugs increased the number of Treg cells
      with suppression function only in the presence of TGFbeta, 75 drugs increased
      Treg numbers even in the absence of TGFbeta, and 32 drugs increased Treg numbers
      synergistically with TGFbeta. The identified Treg-promoting drugs include those
      previously known to induce Treg (rapamycin and retinoic acid), statins,
      glucocorticoids and drugs in many other categories. Furthermore, Treg cells
      cultured with the identified drugs possess surface and intracellular markers
      characteristic of natural Treg cells and possess suppressive function. These
      results suggest that this Treg HTS assay can be used to screen compound libraries
      to identify novel chemical entities for Treg-based immune therapies.

PMID- 23537701
TI  - An ultra-low dose of tetrahydrocannabinol provides cardioprotection.
AB  - Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, is a
      cannabinoid agonist that exerts its effects by activating at least two specific
      receptors (CB1 and CB2) that belong to the seven transmembrane G-protein coupled
      receptor (GPCR) family. Both CB1 and CB2 mRNA and proteins are present in the
      heart. THC treatment was beneficial against hypoxia in neonatal cardiomyocytes in
      vitro. We also observed a neuroprotective effect of an ultra low dose of THC when
      applied to mice before brain insults. The present study was aimed to test and
      characterize the cardioprotective effects of a very low dose (0.002mg/kg) of THC
      which is 3-4 orders of magnitude lower than the conventional doses, administered
      before myocardial infarction in mice in vivo. Three regimens of THC
      administration were tested: single THC application 2h or 48h before the induction
      of infarct, or 3 weeks continuous treatment before MI. All protocols of THC
      administration were found to be beneficial. In the case of THC treatment 2h
      before MI, fractional shortening was elevated (37+/-4% vs. 42+/-1%, p<0.04),
      troponin T leakage to the blood was reduced (14+/-3ng/ml vs. 10+/-4ng/ml,
      p<0.008), infarct size decreased (29+/-4% vs. 23+/-4%, p<0.02), and the
      accumulation of neutrophils to the infarct area declined (36+/-10cells/field vs.
      19+/-4cells/field, p<0.007) in THC- compared to vehicle-pretreated mice, 24h
      after MI. ERK1/2 phosphorylation following infarct was also inhibited by pre
      treatment with THC (p<0.01). CONCLUSION: A single ultra low dose of THC before
      ischemia is a safe and effective treatment that reduces myocardial ischemic
      damage.

PMID- 23537703
TI  - [Quarterly Medical Review, two years after...].

PMID- 23537704
TI  - Optimizing desalinated sea water blending with other sources to meet magnesium
      requirements for potable and irrigation waters.
AB  - Sea water desalination provides fresh water that typically lacks minerals
      essential to human health and to agricultural productivity. Thus the rising
      proportion of desalinated sea water consumed by both the domestic and
      agricultural sectors constitutes a public health risk. Research on low-magnesium
      water irrigation showed that crops developed magnesium deficiency symptoms that
      could lead to plant death, and tomato yields were reduced by 10-15%. The World
      Health Organization (WHO) reported on a relationship between sudden cardiac death
      rates and magnesium intake deficits. An optimization model, developed and tested
      to provide recommendations for Water Distribution System (WDS) quality control in
      terms of meeting optimal water quality requirements, was run in computational
      experiments based on an actual regional WDS. The expected magnesium deficit due
      to the operation of a large Sea Water Desalination Plant (SWDP) was simulated,
      and an optimal operation policy, in which remineralization at the SWDP was
      combined with blending desalinated and natural water to achieve the required
      quality, was generated. The effects of remineralization costs and WDS physical
      layout on the optimal policy were examined by sensitivity analysis. As part of
      the sensitivity blending natural and desalinated water near the treatment plants
      will be feasible up to 16.2 US cents/m(3), considering all expenses. Additional
      chemical injection was used to meet quality criteria when blending was not
      feasible.

PMID- 23537705
TI  - Two aquaporins of Jatropha are regulated differentially during drought stress and
      subsequent recovery.
AB  - Jatropha has potential to be an important bio-fuel crop due to such advantages as
      high seed oil content and the ability to grow well on marginal lands less suited
      for food crops. Despite its ability to grow on marginal land, Jatropha is still
      susceptible to high salt and drought stresses, which can significantly reduce
      plant growth, stomatal conductance, sap-flow rate, and plant sap volume. This
      study was undertaken to collect basic knowledge of the physiological and
      molecular aspects of Jatropha response to salt and drought stresses, and to
      elucidate how Jatropha recovers from stress. From these studies we identified
      candidate genes that may be useful for the development of Jatropha cultivars that
      will grow efficiently in arid and barren lands. Of particular interest, two
      plasma membrane intrinsic proteins were identified: Jatropha plasma membrane
      intrinsic protein 1 (JcPIP1) and Jatropha plasma membrane intrinsic protein 2
      (JcPIP2). The expression levels of JcPIP1 were dramatically increased in roots,
      stems, and leaves during the recovery from stress, whereas the JcPIP2 gene
      transcripts levels were induced in roots and stems during the water deficit
      stress. The protein levels of JcPIP1 and JcPIP2 were consistent with the gene
      expression patterns. Based on these results, we hypothesized that JcPIP1 plays a
      role in the recovery events from water stresses, while JcPIP2 is important in
      early responses to water stress. Virus induced gene silencing technology revealed
      that both JcPIP1 and JcPIP2 have positive roles in response to water deficit
      stresses, but have antagonistic functions at the recovery stage. We suggest that
      both JcPIP1 and JcPIP2 may play important roles in responses to water deficit
      conditions and both have potential as targets for genetic engineering.

PMID- 23537706
TI  - Rye oxidative stress under long term Al exposure.
AB  - Aluminium (Al) toxicity decreases plant growth. Secale cereale L. is among the
      most Al-tolerant crop species. In order to study the response to Al-long term
      exposure, two rye genotypes with different Al sensitivity ('D. Zlote' and
      'Riodeva') were exposed to 1.11 and 1.85mM Al and the antioxidant responses were
      followed for 2 and 3 weeks in roots and leaves. Al toxicity signals, such as a
      severe decrease in root growth, occurred sooner in 'Riodeva.' The antioxidant
      response was dependent on the genotype, the organ, Al concentration and the
      exposure period. Al-exposed roots of 'D. Zlote' showed earlier enhancements of
      APX, SOD and G-POX activities than those of 'Riodeva.' 'D. Zlote' roots showed
      stimulation of the AsA-GSH cycle after the second week (when root growth
      inhibition was less severe), while later (when severe root growth inhibition was
      observed), oxidation of AsA and GSH pools was observed. In leaves of both
      genotypes, CAT, SOD and G-POX activities increased with Al exposure. In these
      leaves, the effect of AsA-GSH was time dependent, with maximum oxidation at the
      second week, followed by recovery. We confirmed that the oxidation state of AsA
      and GSH pools is involved in the detoxification of Al-induced oxidative stress.
      Moreover, our data demonstrate that the production of ROS does not correlate with
      the Al-induced root growth decrease. Finally, the differences observed over time
      indicate that long term exposure may provide additional information on rye
      sensitivity to Al, and contribute to a better understanding of this species'
      mechanisms of Al tolerance.

PMID- 23537707
TI  - Scavenger receptor class A member 3 (SCARA3) in disease progression and therapy
      resistance in multiple myeloma.
AB  - This study evaluates the role of scavenger receptor class A member 3 (SCARA3) in
      multiple myeloma (MM). SCARA3 expression was induced upon treatment with
      oxidative stressors (ionizing radiation and chemotherapeutic drugs). An
      epigenetic inactivation of SCARA3 was noted in MM.1S myeloma cells. Myeloma cell
      killing by dexamethasone and bortezomib was inhibited by up-regulation of SCARA3
      while SCARA3 knockdown sensitized myeloma cells to the drugs. Clinical samples
      showed an inverse correlation between SCARA3 gene expression, myeloma
      progression, and favorable clinical prognosis. In MM, SCARA3 protects against
      oxidative stress-induced cell killing and can serve as predictor of MM
      progression and therapeutic response. 

PMID- 23537708
TI  - Etoposide in combination with low-dose CAG (cytarabine, aclarubicin, G-CSF) for
      the treatment of relapsed or refractory acute myeloid leukemia: a multicenter,
      randomized control trial in southwest China.
AB  - In a well-controlled multi-center randomized trial in southwestern China, 228
      patients with refractory or relapsed AML were received a low-dose CAG regimen
      either with etoposide (E-CAG) or without etoposide (CAG). The complete remission
      (CR) rate, overall survival (OS) and toxicity were evaluated. Patients with E-CAG
      had a higher CR rate (71.1% vs. CAG 50.9%, P=0.0002). The tolerability appeared
      to be equivalent. Patients with CR who underwent allogenic hematopoietic stem
      cell transplantation (allo-HSCT) had a higher five-year OS over those without
      allo-HSCT (73.8% vs. 10.8%, P=0.000). The E-CAG regimen is expected to become a
      bridge between relapsed or refractory AML and allo-HSCT.

PMID- 23537709
TI  - Left ventricular mass in HIV-infected patients.
AB  - BACKGROUND: The HIV infection has been associated with an increased incidence of
      vascular events. Left ventricular mass (LVM) is independently associated with
      greater overall mortality. Various studies have shown that patients with HIV
      infection have higher LVM than the uninfected population. We aim to describe the
      distribution of LVM in an extensive series of patients with HIV infection, and
      the factors associated with its increase. PATIENTS AND METHODS: A cross-sectional
      study was performed in HIV-infected patients followed in our center from 1
      December 2009 to 28 February 2011. A transthoracic echocardiography (TTE) was
      performed in all patients who gave their consent. Demographic variables,
      viroimmunological status, cardiovascular risk factors, vascular risk at 10 years
      (VR10) and history of exposure to antiretroviral drugs were collected. LVM was
      considered to be the quantitative dependent variable. A univariate analysis was
      performed, including in the multivariate analysis those variables with P<,05.
      RESULTS: A TTE was performed in 400 patients, and the LVM was calculated in 388.
      Mean age was 45 years, 75.5 males. Mean LVM was 39.54g/m(2.7)(95% CI: 38.35
      40.73). Age, height, body mass index, VR10, hypertension, dyslipidemia, different
      medications within the cardiovascular area and having taken nevirapine have been
      used in the history of the patient were associated to greater LVM. In the
      multivariate analysis, use of nevirapine in the history of the patient and VR10
      remained in the model. CONCLUSIONS: VR10 may be associated with greater LVM. The
      relationship with nevirapine may respond to an indication bias.

PMID- 23537710
TI  - Treatment decisions under ambiguity.
AB  - Many health risks are ambiguous in the sense that reliable and credible
      information about these risks is unavailable. In health economics, ambiguity is
      usually handled through sensitivity analysis, which implicitly assumes that
      people are neutral towards ambiguity. However, empirical evidence suggests that
      people are averse to ambiguity and react strongly to it. This paper studies the
      effects of ambiguity aversion on two classical medical decision problems. If
      there is ambiguity regarding the diagnosis of a patient, ambiguity aversion
      increases the decision maker's propensity to opt for treatment. On the other
      hand, in the case of ambiguity regarding the effects of treatment, ambiguity
      aversion leads to a reduction in the propensity to choose treatment.

PMID- 23537711
TI  - Toxicokinetics of Naja sputatrix (Javan spitting cobra) venom following
      intramuscular and intravenous administrations of the venom into rabbits.
AB  - Existing protocols for antivenom treatment of snake envenomations are generally
      not well optimized due partly to inadequate knowledge of the toxicokinetics of
      venoms. The toxicokinetics of Naja sputatrix (Javan spitting cobra) venom was
      investigated following intravenous and intramuscular injections of the venom into
      rabbits using double-sandwich ELISA. The toxicokinetics of the venom injected
      intravenously fitted a two-compartment model. When the venom was injected
      intramuscularly, the serum concentration-time profile exhibited a more complex
      absorption and/or distribution pattern. Nevertheless, the terminal half-life,
      volume of distribution by area and systemic clearance of the venom injected
      intramuscularly were not significantly different (p > 0.05) from that of the
      venom injected intravenously. The systemic bioavailability of the venom antigens
      injected by intramuscular route was 41.7%. Our toxicokinetic finding is
      consistent with other reports, and may indicate that some cobra venom toxins have
      high affinity for the tissues at the site of injection. Our results suggest that
      the intramuscular route of administration doesn't significantly alter the
      toxicokinetics of N. sputatrix venom although it significantly reduces the
      systemic bioavailability of the venom.

PMID- 23537712
TI  - Didecyldimethylammonium chloride induces pulmonary fibrosis in association with
      TGF-beta signaling in mice.
AB  - Didecyldimethylammonium chloride (DDAC) is a representative dialkyl-quaternary
      ammonium compound that is used as a disinfectant against several pathogens and is
      also used in commercial, industrial, and residential settings. We previously
      investigated toxicity on air way system following single instillation of DDAC to
      the lungs in mice, and found that DDAC causes pulmonary injury, which is
      associated with altered antioxidant antimicrobial responses; the inflammatory
      phase is accompanied or followed by fibrotic response. The present study was
      conducted to monitor transforming growth factor-beta (TGF-beta) signaling in
      pulmonary fibrosis induced by DDAC. Mice were intratracheally instilled with DDAC
      and sacrificed 1, 3, or 7 days after treatment to measure TGF-beta signaling. In
      order to further evaluate TGF-beta signaling, we treated isolated mouse lung
      fibroblasts with DDAC. Fibrotic foci were observed in the lungs on day 3, and
      were widely extended on day 7, with evidence of increased alpha-smooth muscle
      actin-positive mesenchymal cells and upregulation of Type I procollagen mRNA.
      Developing fibrotic foci were likely associated with increased expression of Tgf
      beta1 mRNA, in addition to decreased expression of Bone morphogenetic protein-7
      mRNA. In fibrotic lung samples, the expression of phosphorylated SMAD2/3 was
      considerably higher than that of phosphorylated SMAD1/5. In isolated lung
      fibroblasts, the mRNA levels of Tgf-beta1 were specifically increased by DDAC
      treatment, which prolonged phosphorylation of SMAD2/3. These effects were
      abolished by treatment with SD208 - a TGF-betaRI kinase inhibitor. The results
      suggest that DDAC induces pulmonary fibrosis in association with TGF-beta
      signaling. 

PMID- 23537714
TI  - A DNA microarray for the detection of point mutations and copy number variation
      causing familial hypercholesterolemia in Europe.
AB  - To facilitate genetic cascade screening for familial hypercholesterolemia (FH) in
      Europe, two versions (7 and 9) of a DNA microarray were developed to detect the
      most frequent point mutations in the low-density lipoprotein receptor (LDLR),
      apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9)
      genes. The design of these microarrays is based on LIPOchip, version 4, which
      detects 191 LDLR and APOB mutations identified in Spanish patients with FH. A
      major improvement of LIPOchip, versions 7 and 9, is the ability to detect copy
      number variation (deletions or duplications of entire exons) in LDLR, thus
      abolishing the need to perform multiplex ligase-dependent probe amplification in
      patients with FH. The aim of this study was to validate a tool capable of
      detecting point mutations and copy number variations simultaneously and to
      evaluate its use and the newly developed software for analysis in clinical
      practice by reanalysis of several patients with known mutations causing FH. With
      the help of these validations, several aspects were analyzed, improved, and
      implemented in a newer version, which was evaluated through an internal
      validation.

PMID- 23537715
TI  - Mitral valve repair with Mitrofix device: The real 3D transthoracic
      echocardiogram after three months.

PMID- 23537713
TI  - Melatonin inhibits the caspase-1/cytochrome c/caspase-3 cell death pathway,
      inhibits MT1 receptor loss and delays disease progression in a mouse model of
      amyotrophic lateral sclerosis.
AB  - Caspase-mediated cell death contributes to the pathogenesis of motor neuron
      degeneration in the mutant SOD1(G93A) transgenic mouse model of amyotrophic
      lateral sclerosis (ALS), along with other factors such as inflammation and
      oxidative damage. By screening a drug library, we found that melatonin, a pineal
      hormone, inhibited cytochrome c release in purified mitochondria and prevented
      cell death in cultured neurons. In this study, we evaluated whether melatonin
      would slow disease progression in SOD1(G93A) mice. We demonstrate that melatonin
      significantly delayed disease onset, neurological deterioration and mortality in
      ALS mice. ALS-associated ventral horn atrophy and motor neuron death were also
      inhibited by melatonin treatment. Melatonin inhibited Rip2/caspase-1 pathway
      activation, blocked the release of mitochondrial cytochrome c, and reduced the
      overexpression and activation of caspase-3. Moreover, for the first time, we
      determined that disease progression was associated with the loss of both
      melatonin and the melatonin receptor 1A (MT1) in the spinal cord of ALS mice.
      These results demonstrate that melatonin is neuroprotective in transgenic ALS
      mice, and this protective effect is mediated through its effects on the caspase
      mediated cell death pathway. Furthermore, our data suggest that melatonin and MT1
      receptor loss may play a role in the pathological phenotype observed in ALS. The
      above observations indicate that melatonin and modulation of Rip2/caspase
      1/cytochrome c or MT1 pathways may be promising therapeutic approaches for ALS.

PMID- 23537716
TI  - Estimation of sex from cranial measurements in a Western Australian population.
AB  - It is widely accepted that the most accurate statistical estimations of
      biological attributes in the human skeleton (e.g., sex, age and stature) are
      produced using population-specific standards. As we previously demonstrated that
      the application of foreign standards to Western Australian individuals results in
      an unacceptably large sex bias (females frequently misclassified), the need for
      population-specific standards is duly required and greatly overdue. We report
      here on the first morphometric cranial sexing standards formulated specifically
      for application in, and based on the statistical analysis of, contemporary
      Western Australian individuals. The primary aim is to investigate the nature of
      cranial sexual dimorphism in this population and outline a series of
      statistically robust standards suitable for estimating sex in the complete bone
      and/or associated diagnostic fragments. The sample analysed comprised multi
      detector computed tomography cranial scans of 400 individuals equally distributed
      by sex. Following 3D volume rendering, 31 landmarks were acquired using OsiriX,
      from which a total of 18 linear inter-landmark measurements were calculated.
      Measurements were analysed using basic descriptive statistics and discriminant
      function analyses employing jackknife validations of classification results. All
      measurements (except frontal breadth and orbital height - Bonferroni corrected)
      are sexually dimorphic with sex differences explaining 3.5-48.9% of sample
      variance. Bizygomatic breadth and maximum length of the cranium and the cranial
      base contribute most significantly to sex discrimination; the maximum
      classification accuracy was 90%, with a -2.1% sex-bias. We conclude that the
      cranium is both highly dimorphic and a reliable bone for estimating sex in
      Western Australian individuals.

PMID- 23537717
TI  - Asphyxial death related to postextraction hematoma in an elderly man.
AB  - We here report an autopsy case of a man in his seventies who died from asphyxia
      due to compression of the trachea caused by postextraction bleeding after
      extraction of his left mandibular third molar by a dentist in private practice.
      On the morning after the tooth extraction, he had complained of dyspnea and
      became unconscious at home. Although he was brought to the emergency room by
      ambulance, he died 7 days later without regaining consciousness. Autopsy
      examination revealed that the lingual side of the alveolar bone was fractured at
      the extraction socket. Moreover, subcutaneous bleeding that extended from the
      extraction socket to the thyrohyoid ligament in the cervical region and deviation
      of the epiglottis due to the bleeding were observed. Histological findings
      revealed liver cirrhosis; there were no significant findings in other organs. On
      the basis of these findings, we concluded that alveolar bone fracture occurred
      during the extraction and that the bleeding spread to the cervical region. Thus,
      the patient had died from asphyxia resulting from airway obstruction caused by
      cervical subcutaneous bleeding derived from postextraction bleeding. We emphasize
      that tooth extraction may cause fatal complications in patients with bleeding
      tendencies, particularly in the elderly.

PMID- 23537719
TI  - Pressure wire assessment of hemodynamic alterations after chemoembolization of
      hepatocellular carcinoma.
AB  - RATIONALE AND OBJECTIVES: The end point of chemoembolization for hepatocellular
      carcinoma is qualitative. We intended to determine the feasibility of measuring
      intra-arterial pressure changes after chemoembolization and hypothesized that
      pressures would increase in the distal hepatic artery after the procedure.
      MATERIALS AND METHODS: Before and after chemoembolization, systemic (S) systolic
      and mean pressures were measured along with celiac (C), lobar (L), and distal (D)
      hepatic artery pressures with a pressure wire. Corrected pressures were defined
      as a ratio with S as the denominator to account for intraprocedural S changes.
      Changes in the systolic and mean corrected pressures at each location (C/S, L/S,
      and D/S) were evaluated using paired t tests. Pressure changes in patients with
      and without tumor response using the Modified Response Evaluation Criteria in
      Solid Tumors were also compared. RESULTS: Sixteen tumors were treated in 15
      patients. One patient had bilobar tumors with separate supplying arteries. The
      only significant pressure change was systolic D/S (P = .02), while mean D/S
      approached significance (P = .08). C/S and L/S did not change significantly after
      chemoembolization. Eleven of 16 patients had a complete response, whereas the
      other five had a partial response after chemoembolization. When comparing
      complete to partial responders, no changes in systolic or mean C/S, L/S, or D/S
      reached statistical significance (all P > .05). CONCLUSIONS: Measuring change in
      hepatic artery pressures is feasible. Distal intra-arterial corrected pressures
      increase significantly after chemoembolization. Further study to determine the
      ability to predict tumor necrosis at follow-up imaging is warranted.

PMID- 23537720
TI  - Innovations in coagulation: improved options for treatment of hemophilia A and B.

PMID- 23537721
TI  - Phase I/II, open-label, multicenter, safety, efficacy and PK study of a
      recombinant coagulation factor IX albumin fusion protein (rIX-FP) in subjects
      with hemophilia B.
AB  - Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) is
      a novel recombinant albumin fusion protein designed to extend the half-life of
      recombinant factor IX (rFIX), which is used in the management of hemophilia B.
      Clinical evaluation of rIX-FP in humans is underway, including a recently
      completed phase I/II, open-label, multicenter, study that assessed the safety,
      pharmacokinetics, and efficacy of rIX-FP in patients with severe hemophilia B. A
      total of 17 patients received rIX-FP (25 IU/kg) as either on-demand therapy (n =
      4) for 20 weeks or weekly prophylaxis (n = 13) for up to 44 weeks. Preliminary
      results confirm that rIX-FP has an excellent safety profile and a pharmacokinetic
      profile highlighted by a marked extended half-life, suggesting that weekly
      prophylaxis with rIX-FP at a dose of 25 IU/kg may be appropriate in patients with
      severe hemophilia B, and that extended dosing intervals (10-14 days) may be
      feasible in some patients. A phase II/III study evaluating the safety and
      efficacy of rIX-FP in patients with hemophilia B is underway.

PMID- 23537722
TI  - Bringing new therapy options to the hemophilia community.
AB  - In patients with hemophilia A, outcomes have improved dramatically over the last
      few decades due to several advances in care, including the availability of factor
      VIII (FVIII) concentrates. Current research has focused on enhancing the
      properties of FVIII concentrates and other coagulation factor products using
      recombinant DNA technology. However, there are several challenges to the
      development of new products for hemophilia patients, including the relative
      rarity of the disease, rapidly evolving standards of care, and the varying
      requirements of regulatory authorities around the world. In the development of
      two innovative coagulation factor products (recombinant single-chain factor VIII
      [rVIII-SingleChain] and a recombinant fusion protein linking coagulation factor
      VIIa with albumin [rVIIa-FP]), these issues have been addressed through novel
      clinical trial designs, including an ongoing three-part study evaluating the
      safety, efficacy, and pharmacokinetics of rVIII-SingleChain in patients with
      severe hemophilia A, and a randomized, placebo-controlled, dose-escalation study
      of rVIIa-FP in healthy volunteers. The design of these trials is intended to
      answer as many important clinical questions as possible while limiting the burden
      on hemophilia patients.

PMID- 23537723
TI  - Innovative coagulation factors: albumin fusion technology and recombinant single
      chain factor VIII.
AB  - Albumin fusion technology has been used to enhance the pharmacokinetic properties
      of recombinant coagulation factors. The goal of linking albumin to coagulation
      factors is to extend the half-life of the coagulation factor, thereby allowing
      for less frequent dosing for patients with bleeding disorders, such as
      hemophilia. The novel recombinant fusion proteins linking coagulation factors
      VIIa and IX with albumin (rVIIa-FP and rIX-FP, respectively) have a longer half
      life and similar hemostatic efficacy compared with available recombinant
      coagulation factor products. Clinical evaluation of these fusion proteins is
      underway, and preliminary results with rIX-FP in patients with hemophilia B are
      encouraging. Other advances in coagulation factor therapy include a unique
      recombinant single-chain factor VIII (FVIII) protein, which has improved
      intrinsic stability and a higher affinity for von Willebrand factor (VWF),
      relative to other recombinant FVIIIs, and a recombinant VWF-albumin fusion
      protein (rVWF-FP), which has a significant longer half-life compared to available
      VWF products. Evaluation of these novel recombinant proteins continues and will
      help determine their potential to enhance the management of patients with
      bleeding disorders.

PMID- 23537724
TI  - PROLONG-9FP clinical development program--phase I results of recombinant fusion
      protein linking coagulation factor IX with recombinant albumin (rIX-FP).
AB  - Hemophilia B is a severe bleeding disorder that is characterized by a deficiency
      or dysfunction of coagulation factor IX (FIX). Replacement therapy using
      recombinant or plasma-derived FIX is available, but the relatively short half
      life of FIX (approximately 18 hours) necessitates administration every 2-3 days
      to prevent bleeding episodes. A recombinant fusion protein linking coagulation
      factor IX with albumin, known as rIX-FP, was developed to extend the half-life of
      recombinant FIX and allow for less frequent dosing. In a phase I, multicenter,
      dose-escalation trial (PROLONG-9FP), the safety and pharmacokinetics of rIX-FP
      were assessed in patients with hemophilia B. At a dose of 25-75 IU/kg, rIX-FP was
      well tolerated: no serious adverse events were reported and there was no evidence
      of hypersensitivity or immunogenic reactions. Pharmacokinetic analysis indicated
      enhanced properties, including a 5-fold increase in half-life, 44% higher
      recovery, 7-fold greater area under the curve, and 7-fold slower clearance,
      compared with recombinant FIX. Trough levels were maintained above 5% after 7
      days when rIX-FP was administered at 25 IU/kg and after 14 days when given at 50
      IU/kg, suggesting that schedules involving weekly dosing or dosing every 2 weeks
      are feasible. These results represent the first reported experience with rIX-FP
      in humans, and suggest that rIX-FP therapy is feasible and well tolerated in
      patients with hemophilia B. Phase II/III studies evaluating rIX-FP are underway.

PMID- 23537725
TI  - Novel single-cell functional analysis of red blood cells using laser tweezers
      Raman spectroscopy: application for sickle cell disease.
AB  - Laser tweezers Raman spectroscopy was used to characterize the oxygenation
      response of single normal adult, sickle, and cord blood red blood cells (RBCs) to
      an applied mechanical force. Individual cells were subjected to different forces
      by varying the laser power of a single-beam optical trap, and the intensities of
      several oxygenation-specific Raman spectral peaks were monitored to determine the
      oxygenation state of the cells. For all three cell types, an increase in laser
      power (or mechanical force) induced a greater deoxygenation of the cell. However,
      sickle RBCs deoxygenated more readily than normal RBCs when subjected to the same
      optical forces. Conversely, cord blood RBCs were able to maintain their
      oxygenation better than normal RBCs. These results suggest that differences in
      the chemical or mechanical properties of fetal, normal, and sickle cells affect
      the degree to which applied mechanical forces can deoxygenate the cell.
      Populations of normal, sickle, and cord RBCs were identified and discriminated
      based on this mechanochemical phenomenon. This study demonstrates the potential
      application of laser tweezers Raman spectroscopy as a single-cell, label-free
      analytical tool to characterize the functional (e.g., mechanical deformability,
      oxygen binding) properties of normal and diseased RBCs. 

PMID- 23537726
TI  - Organohalogen contaminants and Blood plasma clinical-chemical parameters in three
      colonies of North Atlantic Great skua (Stercorarius skua).
AB  - The present study compares blood plasma clinical-chemical parameters (BCCPs) in
      birds from three geographically distinct North Atlantic Great skua (Stercorarius
      skua) colonies. Birds from these sites bioaccumulate different POP (persistent
      organic pollutant) concentrations and that enabled us to compare Great skua BCCPs
      in different exposure scenarios. Persistent organic pollutants (organochlorines:
      PCB, DDT, chlordanes, HCB, HCH, mirex and brominated flame retardants: PBDEs) and
      nineteen BCCPs were analysed in 114 adult Great skuas sampled during summer 2009
      in North Atlantic colonies at Bjornoya (n=42), Iceland (n=57) and Shetland
      (n=15). Specimens from Bjornoya had the highest blood plasma concentrations of
      all contaminant groups followed by Iceland and Shetland birds, respectively
      (ANOVA: p<0.05). Most of the 19 BCCP parameters followed the pattern of colony
      differences found for contaminants, with Bjornoya having the highest
      concentrations. However seven BCCPs, the three liver enzymes ALKP, ALAT and GGT
      as well as bile acids, cholesterol, sodium and potassium, did not differ between
      colonies (ANOVA: p>0.05). Therefore correlation analyses of these seven BCCPs vs.
      POPs were done on the combined colony data while the analyses of the remaining 12
      BCCPs were carried out for each colony separately. The analyses of combined
      colony data showed that the blood plasma concentration of liver enzymes ALAT and
      GGT increased with increasing concentrations of SigmaPBDE and SigmaHCH, HCB and
      SigmaCHL, respectively (all Pearson's p<0.05). In Great skuas from Shetland, the
      important osmotic transport protein albumin increased with increasing
      concentrations of SigmaPCB and SigmaDDT, while total blood plasma protein
      increased with SigmaPCB, SigmaDDT, SigmaHCH and HCB concentrations (all Pearson's
      p<0.05). In both Bjornoya and Iceland skuas, blood plasma pancreatic enzyme
      amylase decreased with increasing SigmaHCH concentrations while the erythrocyte
      waste product total bilirubin in blood plasma increased with increasing SigmaHCH
      and SigmaPBDE concentrations in Iceland Great skuas (all Pearson's p<0.05). In
      Bjornoya birds, blood plasma urea from protein metabolism (reflects kidney
      function) increased with increasing SigmaPBDE concentrations (Pearson's p<0.05).
      Furthermore, a redundancy analysis showed that 10.6% of the variations in BCCPs
      could be explained by the variations in POP concentrations. Based on these
      results we suggest that liver and renal functions could be negatively affected by
      different POP compounds. It is, however, uncertain if the colony BCCP differences
      and their relationship to POP concentrations reflect health effects that could
      have an overall impact on the populations via reduced survival and reproduction
      parameters.

PMID- 23537727
TI  - Chronic arsenicosis in cattle: possible mitigation with Zn and Se.
AB  - Supply of arsenic free water in the arsenic endemic zone of West Bengal since a
      long time could not prevent arsenicosis in human completely. So exploration of
      arsenic contamination at all levels of food chain may be important. The report on
      arsenicosis in cattle of arsenic affected zone is scarcely available. In the
      present study, cattle from villages of two arsenic endemic blocks (Chakdah and
      Haringhata) in Nadia district of West Bengal were selected. The cattle affected
      with arsenicosis were identified and isolated. They were divided into two groups:
      untreated control group and treated group-was treated with mixture of zinc oxide
      (10mg/kg) and sodium selenite (0.1mg/kg) orally once daily for 180 days. Milk,
      faeces and hair samples were collected at different time intervals from those
      cattle for analysis of arsenic. Drinking water and straw of those areas were also
      collected for analysis of arsenic. Serum ALT and AST were estimated in collected
      blood samples of the cattle. The untreated control group had shown gradual
      accumulation of total arsenic in hair while the treated group showed a non
      significant but declined accumulation of arsenic in hair from 90th day onwards
      and a significant increase (p<0.05) in total arsenic in faeces from 90th day
      onwards. The arsenic load considerably but non-significantly decreased in milk
      from 60th day onwards in the treated group. Serum AST and ALT activities were
      also decreased in treated cattle. It is concluded that straw is also a major
      source of arsenic contamination in cattle apart from drinking water and arsenic
      may enter into human through consumption of contaminated milk. But zinc and
      selenium mixture may be used to reduce arsenic load in cattle.

PMID- 23537728
TI  - School snacks decrease morbidity in Kenyan schoolchildren: a cluster randomized,
      controlled feeding intervention trial.
AB  - OBJECTIVE: To examine the effects of three different school snacks on morbidity
      outcomes. DESIGN: Twelve schools were randomized to either one of three feeding
      groups or a Control group. There were three schools per group in this cluster
      randomized trial. Children in feeding group schools received school snacks of a
      local plant-based dish, githeri, with meat, milk or extra oil added. The oil used
      was later found to be fortified with retinol. Physical status, food intake and
      morbidity outcomes were assessed longitudinally over two years. SETTING: Rural
      Embu District, Kenya, an area with high prevalence of vitamin A deficiency.
      SUBJECTS: Standard 1 schoolchildren (n 902; analytic sample) enrolled in two
      cohorts from the same schools one year apart. RESULTS: The Meat and Plain Githeri
      (i.e. githeri+oil) groups showed the greatest declines in the probability of a
      morbidity outcome (PMO) for total and severe illnesses, malaria, poor appetite,
      reduced activity, fever and chills. The Meat group showed significantly greater
      declines in PMO for gastroenteritis (mainly diarrhoea) and typhoid compared with
      the Control group, for jaundice compared with the Plain Githeri group, and for
      skin infection compared with the Milk group. The Milk group showed the greatest
      decline in PMO for upper respiratory infection. For nearly all morbidity outcomes
      the Control group had the highest PMO and the least decline over time.
      CONCLUSIONS: The intervention study showed beneficial effects of both animal
      source foods and of vitamin A-fortified oil on morbidity status.

PMID- 23537729
TI  - Protective effects of bilobalide on Abeta(25-35) induced learning and memory
      impairments in male rats.
AB  - Alzheimer's disease (AD) is one of the major neurological diseases of the
      elderly. The deposition of Abeta peptide, which can induce neuronal oxidative
      stress, inflammation and apoptosis, plays important roles in neuronal
      degeneration in AD. Currently, there are no effective drug treatment options for
      preventing or even slowing Alzheimer's disease. Bilobalide (BB) is one of the
      major active compounds extracted from Ginkgo biloba leaves. This study explored
      the neuroprotective effects of BB on Abeta25-35 intrahippocampal injection
      induced AD model in rats. Our results showed that BB (4, 8 mg/kg) significantly
      protected against learning and memory impairments induced by Abeta25-35 in Morris
      water maze. Besides, BB (4, 8 mg/kg) was able to attenuate the neuronal damage
      and apoptosis in frontal cortex and hippocampus CA1 in rats. In addition, the
      inhibition of TNF-alpha and Abeta1-40 expression is also involved in the action
      mechanisms of BB in this experimental model. This study provided an experimental
      basis for the clinical application of BB in AD therapy.

PMID- 23537730
TI  - Activity of nicorandil, a nicotinamide derivative with a nitrate group, in the
      experimental model of pain induced by formaldehyde in mice.
AB  - Nicorandil (2-nicotinamide ethyl nitrate), an antianginal drug characterized by
      the coupling of nicotinamide with a nitric oxide (NO) donor, activates guanylyl
      cyclase and opens ATP-dependent K(+) channels. In the present study, we
      investigated the effects induced by per os (p.o.) administration of nicorandil
      (12.5, 25 or 50 mg/kg) or equimolar doses (corresponding to the highest dose of
      nicorandil) of N-(2-hydroxyethyl) nicotinamide (NHN), its main metabolite, or
      nicotinamide in the model of nociceptive response induced by formaldehyde in
      mice. Nicorandil, but not NHN or nicotinamide, inhibited the second phase of the
      nociceptive response. This activity was observed when nicorandil was administered
      between 30 and 120 min before the injection of formaldehyde. Ipsilateral
      intraplantar injection of nicorandil (125, 250 or 500 MUg/paw) did not inhibit
      the nociceptive response. After p.o. administration of nicorandil (50 mg/kg),
      peak plasma concentrations of this compound and NHN were observed 0.63 and 4 h
      later, respectively. Nicotinamide concentrations were not increased after
      administration of nicorandil. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1
      or 2 mg/kg), a guanylyl cyclase inhibitor, partially attenuated the
      antinociceptive activity of nicorandil. However, this activity was not changed by
      glibenclamide (30 or 60 mg/kg), an inhibitor of ATP-dependent K(+) channels. In
      conclusion, we demonstrated the antinociceptive activity of nicorandil in a model
      of pain that exhibits both a nociceptive and an inflammatory profile. This
      activity is not mediated by nicotinamide or NHN. The coupling of an NO-donor to
      nicotinamide results in a compound with an increased potency. The NO-cGMP
      pathway, but not ATP-dependent K(+) channels, partially mediates the
      antinociceptive activity of nicorandil.

PMID- 23537731
TI  - Vulnerability to dietary n-3 polyunsaturated fatty acid deficiency after exposure
      to early stress in rats.
AB  - The exposure to adverse events early in life may affect brain development. Omega
      3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the
      development of mood and anxiety disorders. The aim of this study was to examine
      the interaction between variations in the early environment (handling or maternal
      separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on
      locomotor activity, sucrose preference, forced swimming test and on serum and
      hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized
      into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups.
      Pups were removed from their dams (incubator at 32 degrees C on postnatal days
      (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were
      subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS
      gained weight differently, and animals receiving the n-3 PUFA deficient diet
      gained less weight. MS displayed a higher food consumption and higher consumption
      of sucrose solution during the second hour of exposure to the sucrose preference
      test. No differences were observed in the swimming test. H group had increased
      locomotion and showed a higher response to amfepramone. No significant effect was
      observed on serum BDNF levels. BDNF protein levels were decreased in animals
      receiving the n-3 PUFA deficient diet. We observed that early life environment
      and a mild n-3 PUFA deficiency are able to affect several behavioral aspects
      (food and sucrose consumption and locomotor response), and lead to a differential
      hippocampal BDNF metabolism in adult life.

PMID- 23537732
TI  - Mildronate enhances learning/memory and changes hippocampal protein expression in
      trained rats.
AB  - Previously we demonstrated that mildronate [3-(2,2,2-trimethylhydrazinium)
      propionate dihydrate], a representative of the aza-butyrobetaine class of
      compounds, protects mitochondrial metabolism under conditions such as ischemia.
      Mildronate also acted as a neuroprotective agent in an azidothymidine-induced
      mouse model of neurotoxicity, as well as in a rat model of Parkinson's disease.
      These observations suggest that mildronate may stimulate processes involved in
      cell survival and change expression of proteins involved in neurogenic processes.
      The present study investigated the influence of mildronate on learning and memory
      in the passive avoidance response (PAR) test and the active conditioned avoidance
      response (CAR) test in rats. The CAR test employed also bromodeoxyuridine (BrdU)
      treated animals. Hippocampal cell BrdU incorporation was then
      immunohistochemically assessed in BrdU-treated, CAR-trained rats to identify
      proliferating cells. In addition, the expression of hippocampal proteins which
      could serve as memory enhancement biomarkers was evaluated and compared to non
      trained animals' data. These biomarkers included glutamic acid decarboxylase
      65/67 (GAD65/67), acetylcholine esterase (AChE), growth-associated protein-43
      (GAP-43) and the transcription factor c-jun/activator protein-1 (AP-1). The
      results showed that mildronate enhanced learning/memory formation that coincided
      with the proliferation of neural progenitor cells, changing/regulating of the
      expression of biomarker proteins which are involved in the activation of
      glutamatergic and cholinergic pathways, transcription factors and adhesion
      molecule. The data from our study suggest that mildronate may be useful as a
      possible cognitive enhancer for the treatment of patients with neurodegenerative
      diseases with dementia.

PMID- 23537734
TI  - Standardization of automated interpretation of immunofluorescence tests.

PMID- 23537733
TI  - Proteomic analysis of postsynaptic density in Alzheimer's disease.
AB  - BACKGROUND: The loss of synaptic function is a pivotal mechanism in the
      development of Alzheimer's Disease (AD). Structural changes and loss of
      plasticity in the postsynaptic density (PSD) may contribute to the pathogenesis.
      However, the underlying molecular events triggering synaptic dysfunction remain
      elusive. We report a quantitative proteomic analysis of the PSD from human
      postmortem brain tissues of possible and definite AD cases. METHODS: The analysis
      used both discovery and targeted mass spectrometry approaches and was repeated
      with biological replicates. During the discovery study, we compared several
      hundred proteins in the PSD-enriched fractions and found that 25 proteins were
      differentially regulated in AD. RESULTS: Interestingly, the majority of these
      protein changes were larger in definite AD cases than in possible AD cases. In
      the targeted analysis, we measured the level of 9 core PSD proteins and found
      that only IRSp53 was highly down-regulated in AD. The alteration of selected
      proteins (i.e. internexin and IRSp53) was further validated by immunoblotting
      against 7 control and 8 AD cases. CONCLUSIONS: These results expand our
      understanding of how AD impacts PSD composition, and hints at new hypotheses for
      AD pathogenesis.

PMID- 23537735
TI  - Clinical evaluation of the FreeStyle Precision Pro system.
AB  - BACKGROUND: A new version of international standard (ISO 15197) and CLSI
      Guideline (POCT12) with more stringent accuracy criteria are near publication. We
      evaluated the glucose test performance of the FreeStyle Precision Pro system, a
      new blood glucose monitoring system (BGMS) designed to enhance accuracy for point
      of-care testing (POCT). METHODS: Precision, interference and system accuracy with
      503 blood samples from capillary, venous and arterial sources were evaluated in a
      multicenter study. Study results were analyzed and presented in accordance with
      the specifications and recommendations of the final draft ISO 15197 and the new
      POCT12. RESULTS: The FreeStyle Precision Pro system demonstrated acceptable
      precision (CV <5%), no interference across a hematocrit range of 15-65%, and,
      except for xylose, no interference from 24 of 25 potentially interfering
      substances. It also met all accuracy criteria specified in the final draft ISO
      15197 and POCT12, with 97.3-98.9% of the individual results of various blood
      sample types agreeing within +/-12 mg/dl of the laboratory analyzer values at
      glucose concentrations <100mg/dl and within +/-12.5% of the laboratory analyzer
      values at glucose concentrations >=100 mg/dl. CONCLUSIONS: The FreeStyle
      Precision Pro system met the tighter accuracy requirements, providing a means for
      enhancing accuracy for point-of-care blood glucose monitoring.

PMID- 23537736
TI  - A fresh look at analytical performance specifications from biological variation.

PMID- 23537737
TI  - [Fuller's earth, "banished" from herbicide poisoning].

PMID- 23537738
TI  - [Healthcare resources restrictions and human immunodeficiency virus infection].

PMID- 23537739
TI  - [Optimising tissue donation process in a university hospital: 10 years of
      experience].
AB  - BACKGROUND AND OBJECTIVE: The demand of tissue for transplants requires a
      continuous effort in detecting potential donors and assessing the causes of
      death. We aimed to assess the capacity to optimise tissue donation rates with the
      implementation of an active detection system of hospital deaths alongside a
      comprehensive assessment of the causes of death according to current
      international and local tissue banks' standards. MATERIAL AND METHOD: An early
      and pro-active detection programme of hospital deaths was implemented in 2002.
      The potential increase in donation was analysed according to modified criteria:
      age (80 to 85 years), acceptance of corneal phacoemulsification, autoimmune
      diseases, and sepsis reassessment. During the 2002-2011 decade, the criteria for
      absolute exclusion remained the same. The conversion rate from potential donors
      to actual donors of one or more tissue types was analysed. RESULTS: A total of
      16.531 cases of cardiac arrest were analysed, and 11.191 of the cases fulfilled
      criteria of absolute exclusion. The modification of criteria led to an increase
      of potential donors: 10.4% age factor, 4.5% autoimmune
      diseases/phacoemulsification factor, 11.8% sepsis factor (P<.00). The study
      indicated a total increase of 16% (P<.00). A total of 2.371 successful donations
      were generated. The efficiency to generate donors increased from 11 to 21% during
      the aforementioned decade (P<.00). CONCLUSION: A pro-active detection system of
      hospital deaths combined with a continuous re-assessment of the acceptance
      criteria for each tissue type in the hospital setting leads to an increase in the
      potential donors' rate.

PMID- 23537740
TI  - [Disseminated zygomycosis in a patient with chronic lymphocytic leukemia].

PMID- 23537741
TI  - [Flagellate erythema induced by Shiitake mushroom].

PMID- 23537742
TI  - Large scale purification of the SERCA inhibitor thapsigargin from Thapsia
      garganica L. roots using centrifugal partition chromatography.
AB  - Thapsigargin (Tg) is a selective and irreversible inhibitor of the
      sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)-dependent pump at
      subnanomolecular concentrations. As such, it has become a powerful tool in the
      study of Ca(2+) signaling pathway. Purification of Tg from Thapsia species
      requires repeated chromatographic steps with normal-phase alumina or silica and
      reverse phase chromatography. We thus developed an innovative procedure coupling
      high pressure automatized extraction with centrifugal partition chromatography
      allowing a fast and safe large-scale isolation of highly pure Tg, in two steps
      from Thapsia garganica L. roots. Comparison of influence of extraction
      procedures, storage conditions and harvesting areas on Tg content in different
      Algerian specimens of Thapsia garganica L. roots has been precised by mean of
      HPLC quantification procedure. Highest Tg content were found in the fresh
      material of the sample from Setif area.

PMID- 23537743
TI  - Reversed phase High Performance Liquid Chromatography used for the
      physicochemical and thermodynamic characterization of piceatannol/beta
      cyclodextrin complex.
AB  - Piceatannol is one of resveratrol derivatives having health promoting potential.
      However, its low water-solubility and bioavailability could limit its use in both
      food and pharmaceutical fields. The aim of this work is the study of piceatannol
      complexation by beta-cyclodextrin (beta-CD) in aqueous media. The complex formed
      could improve the bioavailability, the solubility and the stability of
      piceatannol. The method used was based on RP-HPLC in which, beta-CD was added to
      methanol/water mixtures mobile phases. The apparent formation constant of
      piceatannol/beta-cyclodextrin complex was determined. Within the concentration
      interval studied (0-4 mM), whenever the concentration of beta-CD increased,
      retention time of piceatannol decreased; indicating an enhancement of solubility
      due to the formation of the piceatannol/beta-CD complex. The formation constants
      (KF) of the piceatannol/beta-CD complex varied significantly with both the
      methanol concentration in the water-methanol mixture and the temperature.
      Moreover, in all the physicochemical conditions tested, the stoichiometry of
      piceatannol/beta-CD complex was 1:1. Finally, the thermodynamic parameters were
      determined: DeltaG degrees =-13.123 kJ mol(-1), DeltaH degrees =-33. 265 kJ mol(
      1) and DeltaS degrees =-67.559 J mol(-1) K(-1).

PMID- 23537744
TI  - Macrophage activation syndrome associated with co-trimoxazole.

PMID- 23537745
TI  - [SPILF comments on procedures to be proposed in order to preserve antibiotics as
      priceless goods, and fight bacterial resistance spreading].

PMID- 23537746
TI  - The effect of a Cimicifuga racemosa extracts Ze 450 in the treatment of
      climacteric complaints--an observational study.
AB  - BACKGROUND: Root extracts of Cimicifuga racemosa (L.) Nutt. have been
      successfully used in the treatment of climacteric complaints. METHOD: In this
      observational study, Cimicifuga racemosa (CR) extract Ze 450 was studied in 442
      unselected ambulatory female outpatients with menopausal complaints under daily
      practice conditions. Physicians were suggested to treat patients for the first 3
      months with 13 mg/d CR (high dose, HD) and to continue over additional 6 months
      either with this treatment or to switch to 6.5mg/d CR (low dose, LD). The choice
      of treatment and its dose, however, was fully at the discretion of the physician.
      RESULTS: After 3-months treatment with HD, symptom severity (Kupperman Menopause
      Index, KMI) decreased significantly (p<0.001) from baseline values. Continuation
      of treatment with HD or LD decreased total KMI and its sub-item scores further
      (HD, LD: p<0.001). However, more patients (84.9%) responded to HD than to LD
      (78.4%) and showed an improvement of symptoms (p=0.011). CONCLUSION: This
      observational study demonstrated that treatment with CR in unselected patients
      with climacteric complaints under the conditions of daily practice resulted in a
      significant improvement of menopausal symptoms assessed by the total KMI score
      and its sub-item scores with an effect size similar to that in a previous
      randomized, controlled clinical trial.

PMID- 23537747
TI  - Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated
      liver cancer HepG2 cells.
AB  - Hepatocyte growth factor (HGF), and its receptor, c-Met activation has recently
      been shown to play important roles in cancer invasion and metastasis in a wide
      variety of tumor cells. We use HGF as an invasive inducer of human HepG2 cells to
      investigate the effect of four flavones including apigenin, tricetin, tangeretin,
      and nobiletin on HGF/c-Met-mediated tumor invasion and metastasis. Among them,
      nobiletin markedly inhibited HGF-induced the abilities of the adhesion, invasion,
      and migration by cell-matrix adhesion assay and transwell-chamber
      invasion/migration assay under non-cytotoxic concentrations. Data also showed
      nobiletin inhibited HGF-induced cell scattering and cytoskeleton changed such as
      filopodia and lamellipodia. Furthermore, nobiletin could inhibit HGF-induced the
      membrane localization of phosphorylated c-Met, ERK2, and Akt, but not
      phosphorylated JNK1/2 and p38. Next, nobiletin significantly decreased the levels
      of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells
      concomitantly with a marked reduction on cell invasion and migration. In
      conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving
      both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic
      agents for the treatment of hepatoma.

PMID- 23537748
TI  - Synergistic antibacterial effect of curcumin against methicillin-resistant
      Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) are spread among infected
      patients, with infection rates increasing at an alarming rate. Furthermore,
      increased resistance to antibiotics has resulted in serious challenges in the
      treatment of infectious diseases worldwide. Under the selection pressure of
      exposure to antibiotics, microorganisms evolve to survive against the new
      conditions imposed by therapy. Therefore, there exists a need to develop
      alternative natural or combination drug therapies. Curcumin (CCM), a natural
      polyphenolic flavonoid isolated from the rhizome of a plant, Curcuma longa
      Linne., has been found to possess many beneficial biological activities. The aim
      of this study was to investigate the synergistic effect of curcumin and
      antibiotics as well as to determine the antibacterial activity of CCM against
      specific MRSA strains. The antibacterial activity of CCM was assessed by the
      broth microdilution method (by calculating the minimal inhibitory concentration
      [MIC]), checkerboard dilution test, and time-kill assay. Antimicrobial activity
      of CCM was observed against all tested strains. The MICs of CCM against 10
      strains of S. aureus ranged from 125 to 250 MUg/ml. In the checkerboard test, CCM
      markedly reduced the MICs of the antibiotics oxacillin (OXI), ampicillin (AMP),
      ciprofloxacin (CIP), and norfloxacin (NOR) used against MRSA. The time-kill
      curves showed that a combined CCM and OXI treatment reduced the bacterial counts
      below the lowest detectable limit after 24h. This study suggested that CCM
      reduced the MICs of several antibiotics tested, notably of OXI, AMP, CIP, and
      NOR, and that CCM in combination with antibiotics could lead to the development
      of new combination of antibiotics against MRSA infection.

PMID- 23537749
TI  - Combination of essential oils and antibiotics reduce antibiotic resistance in
      plasmid-conferred multidrug resistant bacteria.
AB  - In this study we investigated the relationship between several selected
      commercially available essential oils and beta-lactam antibiotics on their
      antibacterial effect against multidrug resistant bacteria. The antibacterial
      activity of essential oils and antibiotics was assessed using broth
      microdilution. The combined effects between essential oils of cinnamon bark,
      lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin,
      cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the
      checkerboard method against beta-lactamase-producing Escherichia coli. In the
      latter assays, fractional inhibitory concentration (FIC) values were calculated
      to characterize interaction between the combinations. Substantial susceptibility
      of the bacteria toward natural antibiotics and a considerable reduction in the
      minimum inhibitory concentrations (MIC) of the antibiotics were noted in some
      paired combinations of antibiotics and essential oils. Out of 35 antibiotic
      essential oil pairs tested, four of them showed synergistic effect (FIC<=0.5) and
      31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained
      highlighted the occurrence of a pronounced synergistic relationship between
      piperacillin/cinnamon bark oil, piperacillin/lavender oil,
      piperacillin/peppermint oil as well as meropenem/peppermint oil against two of
      the three bacteria under study with a FIC index in the range 0.26-0.5. The
      finding highlighted the potential of peppermint, cinnamon bark and lavender
      essential oils being as antibiotic resistance modifying agent. Reduced usage of
      antibiotics could be employed as a treatment strategy to decrease the adverse
      effects and possibly to reverse the beta-lactam antibiotic resistance.

PMID- 23537750
TI  - [Split-dose sodium picosulphate/magnesium citrate for morning colonoscopies
      performed 2 to 6 hours after fluid intake].
AB  - BACKGROUND: Split dosage of bowel preparations has been shown to substantially
      improve bowel cleansing. AIM: To compare the split dose (SD) sodium
      picosulphate/magnesium oxide/anhydrous citric acid (Citrafleet((r))) regimen for
      morning colonoscopies with standard cleansing the day before. METHODS:
      Consecutive outpatients were randomized to receive Citrafleet((r)) the day before
      colonoscopy or SD, in whom the second half was administered on an individual
      basis from 2 to 6 hours before the procedure. No bisacodyl was administered. All
      procedures were performed with non-anesthesiologist administered propofol
      sedation. The Boston scale was used to assess the quality of bowel preparation
      (adequate cleansing if score >= 6, with no score of 0/1 in any segment). RESULTS:
      A total of 193 patients were included. Overall bowel cleansing was significantly
      better in the SD group (7 vs. 5.2, p<0.001), as well as in the cecum (2.4 vs.
      1.4, p < 0.001), ascending colon (2.5 vs. 1.6, p<0.001) and transverse colon (2.4
      vs. 2, p=0.004). A significant proportion of SD patients had adequate bowel
      cleansing (71% vs. 30%, p<0.001). Patients in the SD group drank a greater amount
      of liquid (4.9 vs. 4 liters, p=0.006) and more frequently perceived the cleansing
      process to be easy or very easy to complete (89 vs. 68%, p=0.04), although they
      slept significantly fewer hours (6.5 vs. 7.9, p<0.001). No bronchoaspiration
      pneumonia was reported. CONCLUSIONS: SD Citrafleet((r)) 2 to 6 hours before
      colonoscopy increased the rate of procedures with adequate bowel cleansing by
      40%, especially in the proximal colon, allowed more liquids to be drunk and
      increased the perception of ease in completing the preparation, with no sedation
      related complications.

PMID- 23537751
TI  - [Liver steatosis, insulin resistance and hypobetalipoproteinemia].

PMID- 23537752
TI  - microRNAs as pharmacological targets in cancer.
AB  - The survival rate of cancer patients has increased considerably in the last 20
      years owing to significant efforts made in prevention, early detection protocols,
      combined chemotherapy regimens, targeted therapies, refined radiotherapy and
      cancer vaccines. However, metastasis and acquired resistance to current therapies
      represent two major challenges for achieving long-term cure. Therefore, new
      treatment strategies must be developed. One promising alternative is epigenetic
      based therapies, of which miRNAs are at the forefront. MicroRNAs are endogenous
      small non-coding RNAs, often deregulated in cancer, which regulate gene
      expression by specific binding to the 3'-UTR of target genes. They are excellent
      candidates for therapy since miRNAs can regulate multiple targets of the same or
      different pathways, thereby minimizing the risk of resistance development or
      compensatory mechanisms. In this review, the mechanisms that lead to miRNA
      deregulation in cancer, their feasibility as therapeutic tools and the different
      strategies for the pharmacological manipulation of miRNAs in preclinical animal
      models are discussed. 

PMID- 23537753
TI  - Advances in stem cell therapy against gliomas.
AB  - Malignant gliomas are one of the most lethal cancers, and despite extensive
      research very little progress has been made in improving prognosis. Multimodality
      treatment combining surgery, radiation, and chemotherapy is the current gold
      standard, but effective treatment remains difficult due to the invasive nature
      and high recurrence of gliomas. Stem cell-based therapy using neural,
      mesenchymal, or hematopoietic stem cells may be an alternative approach because
      it is tumor selective and allows targeted therapy that spares healthy brain
      tissue. Stem cells can be used to establish a long-term antitumor response by
      stimulating the immune system and delivering prodrug, metabolizing genes, or
      oncolytic viruses. In this review, we discuss current trends and the latest
      developments in stem cell therapy against malignant gliomas from both the
      experimental laboratory and the clinic.

PMID- 23537754
TI  - Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.
AB  - Economic evaluations of health interventions pose a particular challenge for
      reporting. There is also a need to consolidate and update existing guidelines and
      promote their use in a user friendly manner. The Consolidated Health Economic
      Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate
      and update previous health economic evaluation guidelines efforts into one
      current, useful reporting guidance. The primary audiences for the CHEERS
      statement are researchers reporting economic evaluations and the editors and peer
      reviewers assessing them for publication. The need for new reporting guidance was
      identified by a survey of medical editors. A list of possible items based on a
      systematic review was created. A two round, modified Delphi panel consisting of
      representatives from academia, clinical practice, industry, government, and the
      editorial community was conducted. Out of 44 candidate items, 24 items and
      accompanying recommendations were developed. The recommendations are contained in
      a user friendly, 24 item checklist. A copy of the statement, accompanying
      checklist, and this report can be found on the ISPOR Health Economic Evaluations
      Publication Guidelines Task Force website:
      (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to
      better reporting, and ultimately, better health decisions. To facilitate
      dissemination and uptake, the CHEERS statement is being co-published across 10
      health economics and medical journals. We encourage other journals and groups, to
      endorse CHEERS. The author team plans to review the checklist for an update in
      five years.

PMID- 23537755
TI  - Relatedness calculations for linked loci incorporating subpopulation effects.
AB  - Often the loci in forensic multiplexes are selected to avoid linked loci. However
      linked loci have occurred in some recent commercially available multiplexes.
      Previously formulae have been given for both joint and conditional match
      probabilities for some relationships that did not account for subpopulation
      effects. In this paper we extend these works to include a subpopulation
      correction of the form first suggested by Balding and Nichols. We extend the work
      to grandparent/grandchild, first cousin, uncle/nephew and half uncle/nephew
      relationships and apply these to two different populations and STR multiplexes.
      Our model assumes that the two people have no relationship other that the one
      specified. That is, we assume their parents are neither related nor themselves
      inbred. The multiplications inherent in these formulae also assume that there is
      no linkage disequilibrium at the subpopulation level for these loci. We found
      that when taking into account linkage the match statistic decreases for all
      relationships, with siblings having the greatest effect. However, the effect was
      less than a factor of two decrease in match statistic.

PMID- 23537756
TI  - Eurasiaplex: a forensic SNP assay for differentiating European and South Asian
      ancestries.
AB  - We have selected a set of single nucleotide polymorphisms (SNPs) with the
      specific aim of differentiating European and South Asian ancestries. The SNPs
      were combined into a 23-plex SNaPshot primer extension assay: Eurasiaplex,
      designed to complement an existing 34-plex forensic ancestry test with both
      marker sets occupying well-spaced genomic positions, enabling their combination
      as single profile submissions to the Bayesian Snipper forensic ancestry inference
      system. We analyzed the ability of Eurasiaplex plus 34plex SNPs to assign
      ancestry to a total 1648 profiles from 16 European, 7 Middle East, 13 Central
      South Asian and 21 East Asian populations. Ancestry assignment likelihoods were
      estimated from Snipper using training sets of five-group data (three Eurasian
      groups, East Asian and African genotypes) and four-group data (Middle East
      genotypes removed). Five-group differentiations gave assignment success of 91%
      for NW European populations, 72% for Middle East populations and 39% for Central
      South Asian populations, indicating Middle East individuals are not reliably
      differentiated from either Europeans or Central-South Asians. Four-group
      differentiations provided markedly improved assignment success rates of 97% for
      most continental Europeans tested (excluding Turkish and Adygei at the far
      eastern edge of Europe) and 95% for Central-South Asians, despite applying a
      probability threshold for the highest likelihood ratio above '100 times more
      likely'. As part of the assessment of the sensitivity of Eurasiaplex to analyze
      challenging forensic material we detail Eurasiaplex and 34-plex SNP typing to
      infer ancestry of a cranium recovered from the sea, achieving 82% SNP genotype
      completeness. Therefore, Eurasiaplex provides an informative and forensically
      robust approach to the differentiation of European and South Asian ancestries
      amongst Eurasian populations.

PMID- 23537757
TI  - Clinical outcomes of sacral neuromodulation in patients with neurologic
      conditions.
AB  - OBJECTIVE: To examine the outcomes in patients with and without a comorbid
      neurologic diagnosis (ND) or neurogenic bladder dysfunction after a staged
      neuromodulation procedure for refractory bladder symptoms. MATERIALS AND METHODS:
      Patients enrolled in our prospective neuromodulation database study were grouped
      according to the presence of a coexisting ND. The implantable pulse generator
      implant rates were evaluated. Those who had received an implantable pulse
      generator were further evaluated over time for complications, revisions,
      explantations, and reprogramming sessions collected from the medical records. The
      symptom changes from baseline over 2 years were measured using patient-completed
      voiding diaries, the Interstitial Cystitis Symptom-Problem Index, Overactive
      Bladder Questionnaire, the Medical Outcomes Study short form, 12-item health
      survey, version 2, physical and mental component subscales, and a scaled global
      response assessment. The data were examined using Pearson's chi-square test or
      Fisher's exact test, Wilcoxon rank tests, and repeated measures analyses.
      RESULTS: Of 340 patients, 63 of 71 (88.7%) with an ND and 241 of 269 (89.6%)
      without an ND had an implantable pulse generator implanted (P = .82). The NDs
      consisted of stroke (n = 17), multiple sclerosis (n = 13), Parkinson's disease (n
      = 10), incomplete spinal cord injury (n = 4), cerebral palsy (n = 1), and others.
      The complications, revisions/explants, and reprogramming sessions were similar
      between the 2 groups. Statistically significant improvements were seen in both
      groups over time on the voiding diary variables (except for incontinence episodes
      and severity in the ND group), Interstitial Cystitis Symptom-Problem Index, and
      Overactive Bladder Questionnaire. The short form, 12-item, physical and mental
      component subscale scores only improved significantly in those without an ND.
      Most patients (>50%) in both groups reported moderate or marked improvement in
      overall bladder symptoms at each point using the global response assessments.
      CONCLUSION: Patients with neurogenic bladder dysfunction experience benefits
      after neuromodulation similar to the benefits experienced by those without
      coexisting neurologic conditions.

PMID- 23537758
TI  - Editorial comment.

PMID- 23537761
TI  - Editorial comment.

PMID- 23537760
TI  - Hook wire localization for testis sparing surgery.
AB  - OBJECTIVE: To describe a novel technique for localizing small testicular mass
      during testicular-sparing surgery (TSS). METHODS AND RESULTS: A 20-year-old man
      presented with bilateral testicular masses. Both alpha-fetoprotein (AFP) and beta
      human chorionic gonadotropin (BHCG) levels were raised. Clinical and imaging
      studies revealed a 2.7 cm and 0.7 cm mass in the right and left testis,
      respectively. No metastatic disease was detected on staging scans. Right inguinal
      total orchiectomy was performed. For the left testis, the inguinal approach was
      used to deliver the testis to the surgical wound. Vascular clamping and cooling
      of the testis were performed. A hook wire (Ghiatas Beaded Breast Localization
      Wire, 20G) was then inserted through the small testicular tumor with the aid of
      on-table ultrasound imaging. Testicular-sparing surgery (TSS) was easily
      performed with the aid of the hook wire. Postoperative recovery was uneventful.
      The histology report revealed a mixed germ cell tumor with clear margin. Tumor
      markers returned to normal after surgery. Serum testosterone level was also
      within normal range. Follow-up ultrasound scan showed a viable left testis with
      normal vascularity. CONCLUSION: Hook wire localization of a small testicular mass
      under ultrasound guidance is an easy-to-perform technique that facilitates TSS in
      selected patients. This technique allows TSS to be performed in a more controlled
      and confident manner.

PMID- 23537763
TI  - Cystinuria crystals: an image from a 14-year-old girl with cystinuria.
AB  - The image we present demonstrates the classic hexagonal crystals that are
      diagnostic of cysteine crystals in a 14-year-old girl with cystinuria. These
      crystals developed on her stent within a 2-week period after treatment of her
      stone. The image illustrates the importance of urine microscopy and basic
      urologic knowledge.

PMID- 23537764
TI  - The different breeding strategies of penguins: a review.
AB  - The 18 penguin species are exclusively and widely distributed in the Southern
      hemisphere, from the Equator to the Antarctic continent, and are thus submitted
      to various ecological constraints in their reproductive strategy. This results in
      a high variability in all aspects of the breeding biology of the different
      species. Although penguins appear primarily adapted for a marine existence, they
      remain dependent on land for breeding, rearing young, and moulting. Here we
      describe and compare the breeding cycle of all the penguin species, highlighting
      the characteristics of each species in terms of breeding range, population
      status, threats induced by environmental changes, duration of the different
      phases of the breeding cycle, mate fidelity, body mass, body height, egg mass and
      duration of egg formation. We also focus on the breeding cycle of the genus
      Aptenodytes, since it largely differs from the breeding cycle of most of the
      other penguin species.

PMID- 23537765
TI  - Does a quorum sensing mechanism direct the behavior of immune cells?
AB  - Quorum sensing is a decision-making process used by decentralized groups such as
      colonies of bacteria to trigger a coordinated behavior. The existence of
      decentralized coordinated behavior has also been suggested in the immune system.
      In this paper, we explore the possibility for quorum sensing mechanisms in the
      immune response. Cytokines are good candidates as inducer of quorum sensing
      effects on migration, proliferation and differentiation of immune cells. The
      existence of a quorum sensing mechanism should be explored experimentally. It may
      provide new perspectives into immune responses and could lead to new therapeutic
      strategies.

PMID- 23537766
TI  - Efficient micropropagation and chlorocholine chloride induced stevioside
      production of Stevia rebaudiana Bertoni.
AB  - A promising method of micropropagation of Stevia rebaudiana Bertoni has been
      developed with an aim to increase the biomass, survivability of the plantlets and
      stevioside production, using chlorocholine chloride (CCC). Microshoots
      transferred to the MS medium containing different combinations CCC and IBA were
      found to be most effective in terms of growth pattern, hardening ability of the
      plantlets and stevioside content, compared to MS medium containing either IBA or
      CCC. Among other combinations tested, MS medium supplemented with 3 mg/l CCC and
      3 mg/l IBA was found most effective in inducing significant changes like reduced
      shoot length, increased number of roots, higher leaf size, increased biomass and
      chlorophyll retaining capacity, higher survival percentage and most importantly
      the elevated stevioside content. Collectively, the major observations of this
      research indicate that application of CCC in micropropagation of S. rebaudiana
      Bertoni is a promising approach and has commercial prospects.

PMID- 23537767
TI  - Differentiation of Fanconi anemia and aplastic anemia using mitomycin C test in
      Tunisia.
AB  - Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is
      clinically characterized by multiple symptoms. Chromosome breakage
      hypersensitivity to alkylating agents is the gold standard test for FA diagnosis.
      In this study, we provide a detailed laboratory protocol for accurate assessment
      of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage
      study was successful in 171 out of 205 aplastic anemia (AA) patients. According
      to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as
      affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected
      in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients
      were also evaluated and five of them (19.23%) were diagnosed as FA. From this
      study, a standard protocol for diagnosis of FA was developed. It is routinely
      used as a diagnostic test of FA in Tunisia.

PMID- 23537768
TI  - Combined harvesting of a stage structured prey-predator model incorporating
      cannibalism in competitive environment.
AB  - In this paper, we propose a prey-predator system with stage structure for
      predator. The proposed system incorporates cannibalism for predator populations
      in a competitive environment. The combined fishing effort is considered as
      control used to harvest the populations. The steady states of the system are
      determined and the dynamical behavior of the system is discussed. Local stability
      of the system is analyzed and sufficient conditions are derived for the global
      stability of the system at the positive equilibrium point. The existence of the
      Hopf bifurcation phenomenon is examined at the positive equilibrium point of the
      proposed system. We consider harvesting effort as a control parameter and
      subsequently, characterize the optimal control parameter in order to formulate
      the optimal control problem under the dynamic framework towards optimal
      utilization of the resource. Moreover, the optimal system is solved numerically
      to investigate the sustainability of the ecosystem using an iterative method with
      a Runge-Kutta fourth-order scheme. Simulation results show that the optimal
      control scheme can achieve sustainable ecosystem. Results are analyzed with the
      help of graphical illustrations.

PMID- 23537769
TI  - Analysis of spermiogenesis like a tool in the study of the triatomines of the
      Brasiliensis subcomplex.
AB  - The specific identification and systematic of triatomines have been based
      fundamentally on morphological observations. These organisms are classified into
      complexes and specific subcomplexes, principally for morphological parameters and
      geographical disposition. The use of cytogenetic analyzes has been represented as
      a tool in systematic and taxonomy of triatomines. Thus, the present work, through
      the analysis of spermiogenesis, aims to characterize this stage of
      spermatogenesis in triatomines little studied, and especially to compare it among
      the species Triatoma lenti and T. sherlocki, to assist in the diagnosis of
      differentiation of these insects. The presence of the heteropyknotic corpuscle is
      shown as a diagnostic tool to differentiate T. sherlocki and T. lenti, since it
      is absent in T. lenti. The analysis of the spermiogenesis in T. sherlocki also
      allowed us to address morphological differences between elongating cells, which
      were relatively smaller and more filamentous when compared to T lenti.
      Furthermore, the flagellum was observed in all stages of cell differentiation and
      elongation. This structure, which helps in the locomotion of the sperm, is hardly
      observed in cytogenetic analysis, especially throughout spermiogenesis. Thus,
      although other comparative approaches should be taken, this paper allowed
      emphasizing the analysis of spermiogenesis as an important cytotaxonomic tool
      that assists in the differentiation of morphologically related species, such as
      T. lenti and T. sherlocki.

PMID- 23537770
TI  - A new subgenus and species of Alloscorpiops Vachon, 1980 from Laos (Scorpiones,
      Euscorpiidae, Scorpiopinae); implications for the taxonomy of the group.
AB  - Alloscorpiops (Laoscorpiops) calmonti subgen. n., sp. n., belonging to the family
      Euscorpiidae Laurie, is described on the basis of single female specimen
      collected in the Pathoumphone District of southern Laos. This new scorpion taxon
      may represent yet another endemic element for the fauna of Laos. The new subgenus
      is characterized by a previously unknown and possible unique trichobothrial
      pattern.

PMID- 23537772
TI  - Putting the comparison of 2008 and 2011 appropriate use criteria for stress
      echocardiography in perspective: can screening in solid organ transplant be
      appropriate?

PMID- 23537775
TI  - Should echocardiographers embrace the FOCUS examination?

PMID- 23537771
TI  - American Society of Echocardiography Cardiovascular Technology and Research
      Summit: a roadmap for 2020.

PMID- 23537776
TI  - Predicting percentage body fat through waist-to-height ratio (WtHR) in Spanish
      schoolchildren.
AB  - OBJECTIVE: To analyse the association between waist-to-height ratio (WtHR) and
      body fat and to develop predictive adiposity equations that will simplify the
      diagnosis of obesity in the paediatric age group. DESIGN: Cross-sectional study
      conducted in Spain during 2007 and 2008. Anthropometric dimensions were taken
      according to the International Biology Program. The children were classified as
      underweight, normal weight, overweight or obese according to national standards
      of percentage body fat (%BF). WtHR differences among nutritional status
      categories were evaluated using ANOVA. Correlation analysis and regression
      analysis were carried out using WtHR as a predictor variable for %BF. A t test
      was applied to the results obtained by the regression model and by the Siri
      equation. The degree of agreement between both methods was evaluated by
      estimating the intra-class correlation coefficient. SETTING: Elementary and
      secondary schools in Madrid (Spain). SUBJECTS: Girls (n 1158) and boys (n 1161)
      from 6 to 14 years old. RESULTS: WtHR differed significantly (P < 0.001)
      depending on nutritional status category. This index was correlated (P < 0.001)
      with all adiposity indicators. The mean %BF values estimated by the regression
      model (boys: %BF = 106.50 * WtHR - 28.36; girls: %BF = 89.73 * WtHR - 15.40) did
      not differ from those obtained by the Siri equation. The intra-class correlation
      coefficient (0.85 in boys, 0.79 in girls) showed a high degree of concordance
      between both methods. CONCLUSIONS: WtHR proved to be an effective method for
      predicting relative adiposity in 6-14-year-olds. The developed equations can help
      to simplify the diagnosis of obesity in schoolchildren.

PMID- 23537777
TI  - Calretinin is expressed in the intermediate cells during olfactory receptor
      neuron development.
AB  - The field of neurogenesis has greatly benefited from stage-specific marker
      discoveries. However, such markers are not well defined in the olfactory
      epithelium (OE), where olfactory receptor neurons (ORNs) are constantly generated
      throughout lifetime. During OE neurogenesis, there is a lack of markers that
      label cells that are at the intermediate stage before they are fully mature. In
      this study, we show that during embryonic development calretinin is expressed
      transiently in the intermediate cells right before ORNs become mature. Calretinin
      is expressed between the end of beta-III tubulin (an immature neuronal marker)
      expression and the beginning of olfactory marker protein (OMP, a mature neuronal
      marker) expression in ORNs. Therefore, calretinin can serve as a marker of the
      intermediate ORNs. With this discovery, future studies can use calretinin as a
      tool to define these intermediate ORNs during olfactory neurogenesis.

PMID- 23537778
TI  - Hydrolysis of konjac glucomannan by Trichoderma reesei mannanase and
      endoglucanases Cel7B and Cel5A for the production of glucomannooligosaccharides.
AB  - In this paper we describe the enzymatic hydrolysis of konjac glucomannan for the
      production of glucomannooligosaccharides using purified Trichoderma reesei
      mannanase, endoglucanases EGI (Tr Cel7b) and EGII (Tr Cel5a). Hydrolysis with
      each of the three enzymes produced a different pattern of oligosaccharides.
      Mannanase was the most selective of the three enzymes in the hydrolysis of konjac
      mannan and over 99% of the formed oligosaccharides had mannose as their reducing
      end pyranosyl unit. Tr Cel5A hydrolysate shared similarities with mannanase and
      Tr Cel7B hydrolysates and the enzyme had the lowest substrate specificity of the
      studied enzymes. The hydrolysate of Tr Cel7B contained a series of
      oligosaccharides with non-reducing end mannose (M) and reducing end glucose (G)
      (MG, MMG, MMMG, and MMMMG). These oligosaccharides were isolated from the
      hydrolysate by size exclusion chromatography in relatively high purity (86-95%)
      and total yield (23% of substrate). The isolated oligosaccharides were
      characterized using acid hydrolysis and HPAEC-PAD (carbohydrate composition),
      HPLC-RI and HPAEC-MS (to determine the DP of purified oligosaccharides),
      enzymatic hydrolysis (determination of non-reducing end carbohydrate) and NMR
      (both 1D and 2D, to verify structure and purity of purified compounds).
      Hydrolysis of konjac mannan with a specific enzyme, such as T. reesei Cel7B or
      mannanase, followed by fractionation with SEC offers the possibility to produce
      glucomannooligosaccharides with defined structure. The isolated oligosaccharides
      can be utilised as analytical standards, for determination of bioactivity of
      oligosaccharides with defined structure or as substrates for defining substrate
      specificity of novel carbohydrate hydrolyzing enzymes.

PMID- 23537779
TI  - Berberine improves insulin resistance in cardiomyocytes via activation of 5'
      adenosine monophosphate-activated protein kinase.
AB  - OBJECTIVE: Insulin resistance plays an important role in the pathogenesis of
      diabetic cardiomyopathy. Berberine (BBR) is a plant alkaloid which promotes
      hypoglycemia via increasing insulin sensitivity in peripheral tissues. Little is
      known of BBR's role in regulating glucose metabolism in heart. MATERIALS/METHODS:
      We examined the effect and mechanism of BBR on glucose consumption and glucose
      uptake in insulin sensitive or insulin resistant rat H9c2 cardiomyocyte cells.
      H9c2 myoblast cells were differentiated into cardiomyocytes and incubated with
      insulin for 24h to induce insulin resistance. RESULTS: BBR-treatment of H9c2
      cells increased glucose consumption and glucose uptake compared to controls. In
      addition, BBR-treatment attenuated the reduction in glucose consumption and
      glucose uptake in insulin resistant H9c2 cells. Compound C, an inhibitor of AMP
      activated protein kinase (AMPK), abolished the enhancement of glucose consumption
      and glucose uptake mediated by BBR in both insulin sensitive and insulin
      resistant H9c2 cells compared to controls. CONCLUSION: BBR significantly
      increased AMPK activity, but had little effect on the activity of protein kinase
      B (AKT) in insulin resistant H9c2 cells, suggesting that berberine improves
      insulin resistance in H9c2 cardiomyocytes at least in part via stimulation of
      AMPK activity.

PMID- 23537780
TI  - Upregulation of blood proBDNF and its receptors in major depression.
AB  - BACKGROUND: In recent decades, the role of brain-derived neurotrophic factor
      (BDNF) in depression has received intensive attention. However, the relationship
      between proBDNF and depression has not been clearly elucidated. METHODS: Forty
      drug-free women patients diagnosed with major depression and 50 healthy female
      controls were enrolled in our study. Peripheral blood was sampled from all the
      subjects. With the blood samples, we assessed the relationship between BDNF and
      major depression from following aspects: the levels of BDNF, proBDNF and their
      receptors in the sera and lymphocytes. The mRNA levels of these factors in
      lymphocytes were also examined. Furthermore, the correlations between each factor
      and the severity of major depression were tested. RESULTS: It was found that: (a)
      the protein and serum levels of proBDNF, sortilin and p75NTR were higher in major
      depressive patients than in healthy controls while mature BDNF and TrkB levels
      were lower; (b) the BDNF, TrkB, sortilin and p75NTR mRNA levels changed in line
      with their protein levels; (c) The levels of mature BDNF and TrkB had negative
      correlations with the major depression severity, and the levels of proBDNF,
      p75NTR and sortilin were positively correlated with the scores of HRSD-21; (d)
      the ratio of proBDNF and mBDNF was imbalanced in major depressive patients.
      CONCLUSION: The balance between the proBDNF/p75NTR/sortilin and mBDNF/TrkB
      signaling pathways appears dysregulated in major depression and both pathways
      should be considered as biomarkers for the major depression LIMITATIONS: More
      cases on both genders should be enrolled in our study. And further works on the
      mechanisms of how BDNF and its receptors are regulated in depression should also
      be carried out.

PMID- 23537781
TI  - Variation in the HTR1A and HTR2A genes and social adjustment in depressed
      patients.
AB  - BACKGROUND: Social adjustment is impaired in depressed patients. The difficulty
      to adjust to social circumstances has been hypothesized to be one of the causes
      of depression, as well as a consequence of the disorder. Genetic variation in the
      serotonin transporter gene has been previously associated with social adjustment
      levels in patients with mood disorders. METHODS: We investigated whether
      variations on the HTR1A (rs6295) and HTR2A (rs7997012) genes were associated with
      levels of social adjustment using the Social Adjustment Scale in two samples of
      depressed patients (total n=156). RESULTS: Patients carrying the GG genotype of
      the HTR2A-rs7997012 showed better social adjustment in areas of work and family
      unit bonding. LIMITATIONS: These findings did not survive correction for multiple
      testing and should be interpreted with caution. CONCLUSION: Our finding is in
      line with previous observations that have associated the G allele of the HTR2A
      rs7997012 with higher rate of antidepressant response. The HTR2A-rs7997012 is
      worthy of further investigation in studies examining factors that are related to
      depression course and outcome.

PMID- 23537782
TI  - Candida nivariensis as an etiologic agent of vulvovaginal candidiasis in a
      tertiary care hospital of New Delhi, India.
AB  - Candida nivariensis is a cryptic species, phenotypically indistinguishable from
      Candida glabrata and identified by molecular methods. Aside its isolation from
      broncho-alveolar lavage, we report for the first time the etiologic role of C.
      nivariensis in 4 patients with vulvovaginal candidiasis. Of 100 phenotypically
      identified C. glabrata isolates originating from vaginal swabs, 4 were identified
      as C. nivariensis by polymerase chain reaction and confirmed by sequencing. All
      of the C. nivariensis isolates exhibited white colonies on CHROMagar.
      Phylogenetic analysis revealed genotypic diversity in the C. nivariensis isolates
      originating from within or outside of India. Barring a solitary C. nivariensis
      isolate with MIC, 16 MUg/mL of fluconazole, the rest were susceptible to
      voriconazole, itraconazole, posaconazole, isavuconazole, amphotericin B, and
      echinocandins. The patient with high fluconazole MIC did not respond to
      fluconazole therapy. It is suggested that the prevalence of this species is
      likely to be much higher than apparent from the sporadic published reports.

PMID- 23537783
TI  - Microbiology of skin and soft tissue infections in the age of community-acquired
      methicillin-resistant Staphylococcus aureus.
AB  - The objectives of this study were to determine the etiology of skin and soft
      tissue infections (SSTIs) in a general population, and to describe patient
      characteristics, SSTI types, frequency of microbiologic testing, and the role of
      methicillin-resistant Staphylococcus aureus (MRSA) over time. Using electronic
      databases, we identified SSTI episodes and microbiologic testing among members of
      a large US health plan. Between 2006 and 2009, 648699 SSTI episodes were
      identified, of which 23% had a specimen, of which 15% were blood. A pathogen was
      identified in 58% of SSTI cultures. S. aureus was the most common pathogen (80%
      of positive cultures). Half of S. aureus isolates were MRSA. Among cellulitis and
      abscess episodes with a positive blood culture, 21% were methicillin-sensitive S.
      aureus, 16% were MRSA, 21% were beta-hemolytic streptococci and 28% were Gram
      negative bacteria. Between 1998 and 2009, the percentage of SSTIs for which a
      culture was obtained increased from 11% to 24%. In SSTI episodes with a culture
      confirmed pathogen, MRSA increased from 5% in 1998 to 9% in 2001 to 42% in 2005,
      decreasing to 37% in 2009. These data can inform the choice of antibiotics for
      treatment of SSTIs.

PMID- 23537784
TI  - Use of an enzyme-linked immunosorbent assay that utilizes the Tc13Tul antigen of
      Trypanosoma cruzi to monitor patients after treatment with benznidazole.
AB  - Tc13Tul antigen is expressed in the mammalian stages of Trypanosoma cruzi, the
      etiological agent of Chagas' disease. Here, we designed and validated an enzyme
      linked immunosorbent assay using the recombinant Tc13Tul (Tc13Tul-ELISA) and
      found that it had 82.5% sensitivity and 97.05% of specificity. To evaluate
      whether the decrease in antibodies against Tc13Tul may be used as an early marker
      of the effect of chemotherapy with benznidazole, sera from 30 T. cruzi-infected
      children were evaluated by Tc13Tul-ELISA before and after benznidazole treatment.
      While in Group A (6 months-4 years old, n = 16) the decrease of more than 30% of
      Tc13Tul-ELISA values showed a sensitivity similar to that of conventional
      serology (CS); in Group B, (5-12 years old, n = 14) the decrease of Tc13Tul-ELISA
      values was a better parameter than negativization of CS to monitor the impact of
      treatment. Therefore, the dosage of anti-Tc13Tul antibodies may be useful as a
      methodology complementary to CS to evaluate chagasic patients undergoing
      chemotherapy with benznidazole.

PMID- 23537785
TI  - Pneumococcal diagnosis and serotypes in childhood community-acquired pneumonia.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in
      the UK from September 2006 and replaced by PCV13 in 2010. In a prospective study
      from 2009 to 2011 of 160 children aged <=16 years with radiologically confirmed
      pneumonia, likely pneumococcal infections were identified in 26%. Detection of
      pneumococci was improved with polymerase chain reaction compared to culture
      (21.6% versus 6% of children tested, P = 0.0004). Where serotyping was possible,
      all (n = 23) were non-PCV7 but PCV13 serotypes; 1 (43.5%), 3 (21.7%), 7A/F, and
      19A (17.4% each).

PMID- 23537786
TI  - Performance comparison of immunodiffusion, enzyme-linked immunosorbent assay,
      immunochromatography and hemagglutination for serodiagnosis of human pythiosis.
AB  - Pythiosis is a life-threatening infectious disease caused by the fungus-like
      organism Pythium insidiosum. Morbidity and mortality rates of pythiosis are high.
      The treatment of choice for pythiosis is surgical debridement of infected tissue.
      Early and accurate diagnosis is critical for effective treatment. In-house
      serodiagnostic tests, including immunodiffusion (ID), enzyme-linked immunosorbent
      assay (ELISA), immunochromatography (ICT) and hemagglutination (HA) have been
      developed to detect antibodies against P. insidiosum in sera. This study compares
      the diagnostic performance of ID, ELISA, ICT, and HA, using sera from 37
      pythiosis patients and 248 control subjects. ICT and ELISA showed optimal
      diagnostic performance (100% sensitivity, specificity, positive predictive value
      and negative predictive value). ICT was both rapid and user-friendly. ELISA
      results were readily quantitated. ID is relatively insensitive. HA was rapid, but
      diagnostic performance was poor. Understanding the advantages offered by each
      assay facilitates selection of an assay that is circumstance-appropriate. This
      will promote earlier diagnoses and improved outcomes for patients with pythiosis.

PMID- 23537787
TI  - A case of catheter-related bloodstream infection caused by Mycobacterium
      phocaicum.
AB  - We present a patient with double hit Burkitt's like lymphoma who developed a
      catheter-related bloodstream infection due to Mycobacterium phocaicum that was
      identified by rpoB gene sequencing. His infection resolved with 7 weeks of
      antibiotics and port-a-cath removal.

PMID- 23537788
TI  - Impact of identification of Streptococcus dysgalactiae subspecies equisimilis
      from throat cultures in an adult population.
AB  - Streptococcus dysgalactiae subspecies equisimilis (SDSE) are isolated from the
      throat of patients with pharyngitis, although the clinical significance remains
      debated. We sought to determine the incidence and association with pharyngitis of
      SDSE in an adult veteran population. Organisms were phenotypically identified to
      subspecies and Lancefield group, with selective 16S rRNA gene sequencing. From
      833 throat cultures, the overall frequency of SDSE was 3.4% (64% group C and 36%
      group G) as compared to 8.6% for S. pyogenes (GAS). SDSE was described as a large
      colony in only 29% of the original culture evaluations by bench technologists,
      and clinical symptoms were similar for GAS and SDSE. Laboratory algorithms that
      are limited to identification of only GAS or are based on Lancefield group or
      visual identification of "large-colony type" beta hemolytic Lancefield group C
      and G streptococci may be missing or misidentifying SDSE along with Anginosus
      group streptococci.

PMID- 23537789
TI  - Evaluation of 10 serological assays for diagnosing Mycoplasma pneumoniae
      infection.
AB  - In this study, the performance of 10 serological assays for the diagnosis of
      Mycoplasma pneumoniae infection was evaluated. A total of 145 sera from 120
      patients were tested. They were obtained from patients who were serologically
      positive for M. pneumoniae infection as well as from patients who were infected
      with micro-organisms that may cause interstitial pneumonia. The following assays
      were utilized: SeroMP IgM and IgG, SeroMP recombinant IgM, IgA and IgG, Liaison
      M. pneumoniae IgM and IgG and M. pneumoniae IgM, IgA and IgG ELISA Medac. The
      SeroMP Recombinant and Liaison assays both showed low IgM specificity, and
      crossreactivity was mainly observed in groups of patients with acute
      cytomegalovirus and Epstein-Barr virus infections. For IgA, the Medac assay was
      less specific than the SeroMP Recombinant assay. Discrepancies between the four
      tests were observed in IgG analyses, and due to the lack of a gold standard, 22
      results were removed prior to determining the sensitivity and specificity.
      Therefore, the overall performance of IgG assays may be overstated; nevertheless,
      the SeroMP assay demonstrated a lack of sensitivity. The seroprevalence of IgG
      appears to be very low, raising concerns regarding whether the serological
      techniques can detect IgG levels over time. Serology remains a biological tool of
      choice for diagnosing M. pneumoniae infection, but improvement and
      standardization of the assays are needed, particularly for the determination of
      IgG.

PMID- 23537790
TI  - Haemophilus influenzae acute endometritis with bacteremia: case report and
      literature review.
AB  - Haemophilus influenzae rarely causes acute endometritis and the few published
      cases have always been associated with intrauterine devices (IUD). A 48-year-old
      female presented to the emergency department with a 3-day history of lower
      abdominal pain and fever. On physical examination she was tachycardic,
      hypotensive and had fundic tenderness to palpation. Imaging showed uterine
      leiomyomas and no IUD. Blood cultures grew a non-typable H. influenzae.
      Endometrial biopsy demonstrated acute endometritis. Tissue Gram stains and
      cervico-vaginal cultures were negative; however, polymerase chain reaction (PCR)
      determined presence of H. influenzae on the formalin-fixed, paraffin-embedded
      tissue biopsy. Evidence of H. influenzae in the endometrium demonstrates that the
      uterus can be the nidus for sepsis when invasive H. influenzae is found with no
      distinct usual primary focus. This case underscores the importance pathologic
      diagnosis and molecular testing.

PMID- 23537791
TI  - Overproduction of a C5a receptor antagonist (C5aRA) in Escherichia coli.
AB  - The C5aR antagonist (C5aRA)(1), which blocks the interaction of C5a anaphylatoxin
      and its receptor C5aR, is one of the most potent therapeutic agents for the
      treatment of various autoimmune diseases and acute inflammatory conditions. Here
      we developed an efficient C5aRA production system using Escherichia coli. To
      produce functional C5aRA, which contains three disulfide bonds, we used E. coli
      Origami (DE3), which possessed an oxidative cytoplasm, as the production host. To
      improve solubility and ease in purification, we examined the effectiveness of
      three different fusion partners, including N utilization substrate A (NusA),
      maltose-binding protein (MBP), and thioredoxin A (TrxA), as well as three
      different culture temperatures (i.e., 25, 30, and 37 degrees C). Among the three
      fusion partners, MBP exhibited the highest solubility in the fusion protein at
      all tested temperatures. However, the highest biological activity against C5aR
      was observed with the NusA fusion. For large-scale production, batch fermentation
      was also performed using a NusA-fused C5aRA production system by using a lab
      scale bioreactor. After a 12-h cultivation, approximately 496mg/L of NusA-fused
      C5aRA could be produced.

PMID- 23537792
TI  - Chromatographically-purified capsid proteins of red-spotted grouper nervous
      necrosis virus expressed in Saccharomyces cerevisiae form virus-like particles.
AB  - Nervous necrosis viruses (NNVs) cause mass mortality of marine fish, leading to
      large economic losses for aquaculturists. A promising vaccine candidate for
      preventing NNV infection is the NNV virus-like particle (VLP), which is a
      structure resulting from assembly of recombinant NNV capsid protein. NNV capsid
      proteins have been expressed in insect cells and the Escherichia coli expression
      system, and purified by non-scalable protocols such as ultracentrifugation on
      sucrose and cesium chloride density gradients. In this study, we expressed red
      spotted grouper NNV (RGNNV) capsid proteins in Saccharomyces cerevisiae (S.
      cerevisiae) and developed a chromatography-based method with potential for large
      scale vaccine production. The RGNNV capsid protein was successfully purified by a
      single-step of heparin chromatography. Transmission electron microscopy (TEM)
      confirmed the high quality of the purified RGNNV capsid protein: it was in the
      form of VLPs with mean diameters of 25nm, in homogeneous suspension without any
      aggregation. Moreover, the RGNNV capsid protein elicited anti-RGNNV capsid
      protein antibodies in mice. We suggest that RGNNV capsid protein expressed in S.
      cerevisiae and purified by heparin chromatography, is of sufficient quality for
      use as a vaccine.

PMID- 23537793
TI  - "Salt tolerant" anion exchange chromatography for direct capture of an acidic
      protein from CHO cell culture.
AB  - The present study describes the use of the new HyperCel STAR AX "salt tolerant"
      anion exchange sorbent for the capture from Chinese Hamster Ovary (CHO) cell
      culture supernatant (CCS) of an acidic model protein (alpha-amylase). HyperCel
      STAR AX sorbent and other conventional anion exchangers were evaluated to purify
      biologically-active enzyme. Salt tolerance of the sorbent allowed reaching 5-fold
      higher dynamic binding capacity than conventional anion exchange during capture
      of the enzyme from neat (undiluted) CCS. After optimization of operating
      conditions, HyperCel STAR AX turned out to be the only sorbent allowing efficient
      protein capture directly from both neat and diluted CCS with consistent and
      satisfying purity, yield and productivity. Therefore implementation of the salt
      tolerant sorbent in industrial purification processes should allow avoiding time
      and cost consuming steps such as dilution or UF/DF that exclusively aim at
      establishing suitable conditions for ion exchange step without bringing any added
      value to the purification process performance. Altogether this study highlights
      the flexibility and cost-reduction potential brought in process design by the
      HyperCel STAR AX salt tolerant sorbent.

PMID- 23537794
TI  - Coupling predicted model of arsenic in groundwater with endemic arsenism
      occurrence in Shanxi Province, Northern China.
AB  - Statistical modeling has been used to predict high risk area of arsenic (As)
      hazard, but information about its application on endemic arsenism is limited. In
      this study, we aim to link the prediction model with population census data and
      endemic arsenicosis in Shanxi Province, Northern China. 23 explanatory variables
      from different sources were compiled in the format of grid at 1km resolution in a
      GIS environment. Logistic regression was applied to describe the relationship
      between binary-coded As concentrations data and the auxiliary predictors. 61
      endemic arsenism villages were geo-located and combined with output maps of the
      prediction model. Linear regression was used to identify the relationship between
      arsenicosis occurrence rate and predictive As probability at village level. Our
      results show that 6 explanatory environmental variables were significantly
      contributed to the final model. Area of 3000 km(2) was found to have high risk of
      As concentrations above 50 MUg L(-1). The linear regression indicates that 13% of
      the variation in arsenicosis occurrence rate can be predicted using predictive
      probability of As concentration above 50 MUg L(-1) in Shanxi Province. These
      results suggest that As prediction model may be helpful for identifying As
      contaminated area and endemic arsenism village.

PMID- 23537795
TI  - [Delirium in nursing homes. Prevalence and risk factors].
AB  - OBJECTIVES: To study the prevalence of delirium in the residential environment
      and to analyse the associated clinical, functional and mental factors. MATERIAL
      AND METHODS: A cross-sectional epidemic study was conducted on a population of
      elderly persons institutionalised in 2011 in 6 nursing homes in Asturias. Socio
      demographic, clinical, functional (Barthel Index [BI]) and mental (Mini-Mental
      State Examination [MMSE]) variables were collected. Delirium was defined by the
      Confusion Assessment Method. RESULTS: A total of 505 elderly were included in the
      study (age 83.30 +/- 7.33 years, with 67.70% women), and scores on the MMSE of
      17.19 +/- 10.35 and a BI score of 55.11 +/- 35.82. The prevalence of delirium was
      11.70%. On examining the risk of delirium among the studied variables, there was
      statistical significance when considering: BI, MMSE, dementia, pressure ulcers,
      or urinary catheter, and the prescribing of clomethiazole, ACTH-I or trazodone.
      In the analysis of the variables in the logistic regression with BI, diagnosis of
      dementia, the prescribing of clomethiazole or trazodone, in the equation, there
      was a statistical significance associated with delirium. CONCLUSIONS: The
      prevalence of delirium in a residential environment in our study population was
      11.7%. The results show that BI, diagnosis of dementia, and prescribing of
      clomethiazole or trazodone were associated with risk of delirium in
      institutionalised patients.

PMID- 23537796
TI  - False decrease of HBsAg S/CO values in serum with high-concentration rheumatoid
      factors.
AB  - OBJECTIVES: To investigate whether high-concentration RFs cause false decrease of
      S/CO values of serum HBsAg. DESIGN AND METHODS: Serum HBsAg was determined in 100
      RF-positive sera using one-step ELISA. Twenty-three HBsAg-negative sera with high
      concentration RFs were selected randomly to perform dilution with mixed normal
      sera. Serum models consisting of HBsAg and high-concentration RFs were made by
      blending high-concentration RFs and HBsAg-positive sera at the ratio of 9:1.
      RESULTS: In the 23 samples, one-step ELISA showed that HBsAg-positive rate was
      69.57% at dilution of 1:2, 60.87% at dilution of 1:4 and 40.00% at dilution of
      1:8, whereas two-step ELISA showed that it was 100% without any dilution. Thirty
      serum models were made and divided into six groups. Median S/CO value of HBsAg
      was 3.00 in control, whereas it ranged from 0.13 to 1.78 in the six groups.
      CONCLUSIONS: High-concentration RFs cause false decrease of S/CO values of HBsAg
      using one-step ELISA.

PMID- 23537797
TI  - Structural analysis and antioxidant activities of polysaccharides from cultured
      Cordyceps militaris.
AB  - The polysaccharides extracted by hot water and precipitated by 50% ethanol from
      the fruiting bodies of cultured Cordyceps militaris (W-CBP50) were introduced.
      Antioxidant activities of W-CBP50, W-CBP50 I (obtained from W-CBP50 purified by
      Sephadex G-100 chromatography) and W-CBP50 II (obtained from W-CBP50I purified by
      Sephadex G-200 chromatography) were evaluated and structural features of W-CBP50
      II were analyzed. The polysaccharide W-CBP50 II was able to scavenge the stable
      free radical 1,1-diphenyl-2-picrylhyrazyl (DPPH), while W-CBP50 and W-CBP50I
      could scavenge DPPH, hydroxyl and superoxide radical. Structural characteristics
      of W-CBP50 II were investigated using GPC, GC-MS, (1)H NMR and IR. The results
      showed that it was mainly composed of alpha-glucose, alpha-mannose, alpha
      galactose and alpha-arabinose with alpha-type glycosidic linkage and the
      molecular weight of its main component was 8.97 kD.

PMID- 23537798
TI  - Trivalent ion cross-linked pH sensitive alginate-methyl cellulose blend hydrogel
      beads from aqueous template.
AB  - pH sensitive alginate-methyl cellulose blend hydrogel beads were prepared by
      single water-in-water (w/w) emulsion gelation method in a complete aqueous
      environment. The influence of different variables like total polymer
      concentration, gelation time and crosslinker content on in vitro physico-chemical
      characteristics and drug release rate in different medium were investigated. Drug
      loaded beads were evaluated through Fourier Transform Infra-red (FTIR), X-ray
      diffraction (XRD) and Differential Scanning Calorimetry (DSC) analysis. Scanning
      electron microscopy (SEM) picture of the dried beads suggested the formation of
      hemispherical particles. FTIR analysis indicated the stable nature of the drug in
      the blend hydrogel beads. DSC and XRD analysis revealed amorphous state of drug
      after encapsulation. The drug release profile in acidic medium was considerably
      less in compared in alkaline media. Formulations showed non-Fickian type
      transport mechanism. This trivalent ion crosslinked beads not only improves drug
      encapsulation efficiency but also enhances drug release in alkaline media.

PMID- 23537799
TI  - Cytotoxic effect of Agaricus bisporus and Lactarius rufus beta-D-glucans on HepG2
      cells.
AB  - The cytotoxic activity of beta-D-glucans isolated from Agaricus bisporus and
      Lactarius rufus fruiting bodies was evaluated on human hepatocellular carcinoma
      cells (HepG2). NMR and methylation analysis suggest that these beta-d-glucans
      were composed of a linear (1->6)-linked and a branched (1->3), (1->6)-linked
      backbone, respectively. They both decreased cell viability at concentrations of
      up to 100 MUg mL(-1), as shown by MTT assay. The amount of LDH released and the
      analysis of cell morphology corroborated these values and also showed that the
      beta-D-glucan of L. rufus was more cytotoxic to HepG2 cells than that of A.
      bisporus. The treatment of HepG2 cells with L. rufus and A. bisporus beta-D
      glucans at a dose of 200 MUg mL(-1) for 24h promoted an increase of cytochrome c
      release and a decrease of ATP content, suggesting that these polysaccharides
      could promote cell death by apoptosis. Both beta-D-glucans were tested against
      murine primary hepatocytes at a dose of 200 MUg mL(-1). The results suggest that
      the L. rufus beta-d-glucan was as cytotoxic for hepatocytes as for HepG2 cells,
      whereas the A. bisporus beta-D-glucan, under the same conditions, was cytotoxic
      only for HepG2 cells, suggesting cell selectivity. These results open new
      possibilities for use of mushroom beta-D-glucans in cancer therapy.

PMID- 23537800
TI  - Structural characterization of coagulant Moringa oleifera Lectin and its effect
      on hemostatic parameters.
AB  - Lectins are carbohydrate recognition proteins. cMoL, a coagulant Moringa oleifera
      Lectin, was isolated from seeds of the plant. Structural studies revealed a heat
      stable and pH resistant protein with 101 amino acids, 11.67 theoretical pI and
      81% similarity with a M. oleifera flocculent protein. Secondary structure content
      was estimated as 46% alpha-helix, 12% beta-sheets, 17% beta-turns and 25%
      unordered structures belonging to the alpha/beta tertiary structure class. cMoL
      significantly prolonged the time required for blood coagulation, activated
      partial thromboplastin (aPTT) and prothrombin times (PT), but was not so
      effective in prolonging aPTT in asialofetuin presence. cMoL acted as an
      anticoagulant protein on in vitro blood coagulation parameters and at least on
      aPTT, the lectin interacted through the carbohydrate recognition domain.

PMID- 23537801
TI  - Community viral load as a measure for assessment of HIV treatment as prevention.
AB  - Community viral load, defined as an aggregation of individual viral loads of
      people infected with HIV in a specific community, has been proposed as a useful
      measure to monitor HIV treatment uptake and quantify its effect on transmission.
      The first reports of community viral load were published in 2009, and the measure
      was subsequently incorporated into the US National HIV/AIDS Strategy. Although
      intuitively an appealing strategy, measurement of community viral load has
      several theoretical limitations and biases that need further assessment, which
      can be grouped into four categories: issues of selection and measurement, the
      importance of HIV prevalence in determining the potential for ongoing HIV
      transmission, interpretation of community viral load and its effect on ongoing
      HIV transmission in a community, and the ecological fallacy (ie, ecological
      bias). These issues need careful assessment as community viral load is being
      considered as a public health measurement to assess the effect of HIV care on
      prevention.

PMID- 23537802
TI  - Elevated PCSK9 levels in untreated patients with heterozygous or homozygous
      familial hypercholesterolemia and the response to high-dose statin therapy.
AB  - BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) is an enzyme
      that impairs low-density lipoprotein cholesterol (LDL-C) clearance from the
      plasma by promoting LDL receptor degradation. Patients with familial
      hypercholesterolemia (FH) have reduced or absent LDL receptors and should
      therefore have elevated PCSK9 levels. METHODS AND RESULTS: Fasting lipograms and
      PCSK9 levels were measured 51 homozygous FH (HoFH), 20 heterozygous FH (HeFH),
      and 20 normocholesterolemic control subjects. Levels were repeated following high
      dose statin therapy. LDL-C levels were significantly higher in untreated HoFH
      (13.4+/-0.7 mmol/L) and HeFH patients (7.0+/-0.2 mmol/L) compared with controls
      (2.6+/-0.1 mmol/L) (P<0.01). Statin therapy decreased LDL-C levels from 13.4+/
      0.7 to 11.1+/-0.7 mmol/L in HoFH and from 7.0+/-0.2 to 3.6+/-0.2 mmol/L in HeFH
      patients (P<0.01). PCSK9 levels were higher in untreated HoFH (279+/-27 ng/mL)
      and HeFH (202+/-14 ng/mL) than in controls (132+/-10 ng/mL) (both P<0.01). High
      dose statin therapy increased PCSK9 levels from 279+/-27 to 338+/-50 ng/mL in
      HoFH, and significantly so in the HeFH patients from 202+/-14 to 278+/-20 ng/mL
      (P<0.01). Linear regression analysis showed a correlation between PCSK9 and LDL-C
      (r=0.6769; P<0.0001); however, this was eliminated following statin therapy
      (r=0.2972; P=0.0625). CONCLUSIONS: PCSK9 levels are elevated in untreated FH
      patients, particularly in those with HoFH. High-dose statin therapy further
      increases PCSK9 levels. PCSK9 inhibitors might be a beneficial therapy for FH
      patients, even in those with HoFH.

PMID- 23537803
TI  - Mortality From myocardial infarction after the death of a sibling: a nationwide
      follow-up study from Sweden.
AB  - BACKGROUND: Death of a sibling represents a stressful life event and could be a
      potential trigger of myocardial infarction (MI). We studied the association
      between loss of an adult sibling and mortality from MI up to 18 years after
      bereavement. METHODS AND RESULTS: We conducted a follow-up study for Swedes aged
      40 to 69 years between 1981 and 2002, based on register data covering the total
      population (N=1 617 010). Sibling deaths could be observed from 1981 and on. An
      increased mortality rate from MI was found among women (1.25 CI 1.02 to 1.54) and
      men (1.15 CI 1.03 to 1.28) who had experienced death of an adult sibling. An
      elevated rate some years after bereavement was found among both women (during the
      fourth to sixth half-years after the death) and men (during the second to sixth
      half-years after the death), whereas limited support for a short-term elevation
      in the rate was found (during the first few months since bereavement). External
      causes of sibling death were associated with increased MI mortality among women
      (1.54 CI 1.07 to 2.22), whereas nonexternal causes showed associations in men
      (1.23 CI 1.09 to 1.38). However, further analyses showed that if the sibling also
      died from MI, associations were primarily found among both women (1.62 CI 1.00 to
      2.61) and men (1.98 CI 1.59 to 2.48). CONCLUSIONS: Our study provided the first
      large-scale evidence for mortality from MI associated with the death of a sibling
      at an adult age. The fact that findings suggested associations primarily between
      concordant causes of death (both died of MI) could indicate genetic resemblance
      or shared risk factors during childhood. Future studies on bereavement should
      carefully deal with the possibility of residual confounding.

PMID- 23537804
TI  - CD14 directs adventitial macrophage precursor recruitment: role in early
      abdominal aortic aneurysm formation.
AB  - BACKGROUND: Recruitment of macrophage precursors to the adventitia plays a key
      role in the pathogenesis of abdominal aortic aneurysms (AAAs), but molecular
      mechanisms remain undefined. The innate immune signaling molecule CD14 was
      reported to be upregulated in adventitial macrophages in a murine model of AAA
      and in monocytes cocultured with aortic adventitial fibroblasts (AoAf) in vitro,
      concurrent with increased interleukin-6 (IL-6) expression. We hypothesized that
      CD14 plays a crucial role in adventitial macrophage precursor recruitment early
      during AAA formation. METHODS AND RESULTS: CD14(-/-) mice were resistant to AAA
      formation induced by 2 different AAA induction models: aortic elastase infusion
      and systemic angiotensin II (AngII) infusion. CD14 gene deletion led to reduced
      aortic macrophage infiltration and diminished elastin degradation. Adventitial
      monocyte binding to AngII-infused aorta in vitro was dependent on CD14, and
      incubation of human acute monocytic leukemia cell line-1 (THP-1) monocytes with
      IL-6 or conditioned medium from perivascular adipose tissue (PVAT) upregulated
      CD14 expression. Conditioned medium from AoAf and PVAT induced CD14-dependent
      monocyte chemotaxis, which was potentiated by IL-6. CD14 expression in aorta and
      plasma CD14 levels were increased in AAA patients compared with controls.
      CONCLUSIONS: These findings link CD14 innate immune signaling via a novel IL-6
      amplification loop to adventitial macrophage precursor recruitment in the
      pathogenesis of AAA.

PMID- 23537805
TI  - Association of anxiety and depression with all-cause mortality in individuals
      with coronary heart disease.
AB  - BACKGROUND: Depression has been related to mortality in coronary heart disease
      (CHD) patients, but few studies have evaluated the role of anxiety or the role of
      the co-occurrence of depression and anxiety. We examined whether anxiety is
      associated with increased risk of mortality after accounting for depression in
      individuals with established CHD. METHODS AND RESULTS: The cohort was composed of
      934 men and women with confirmed CHD (mean age, 62+/-11 years) who completed the
      Hospital Anxiety and Depression scale (HADS) during hospitalization for coronary
      angiography. Over the 3-year follow-up period, there were 133 deaths. Elevated
      scores on the HADS anxiety subscale (HADS-A>=8) were associated with increased
      risk of mortality after accounting for established risk factors including age,
      congestive heart failure, left ventricular ejection fraction, 3-vessel disease,
      and renal disease (hazard ratio [HR], 2.27; 95% CI, 1.55 to 3.33; P<0.001).
      Elevated scores on the HADS depression subscale (HADS-D>=8) were also associated
      with increased risk of mortality (HR, 2.18; 95% CI, 1.47 to 3.22; P<0.001). When
      both psychosocial factors were included in the model, each maintained an
      association with mortality (anxiety, HR, 1.83; 95% CI, 1.18 to 2.83; P=0.006;
      depression, HR, 1.66; 95% CI, 1.06 to 2.58; P=0.025). Estimation of the HR for
      patients with both anxiety and depression versus those with neither revealed a
      larger HR than for patients with either factor alone (HR, 3.10; 95% CI, 1.95 to
      4.94; P<0.001). CONCLUSIONS: Anxiety is associated with increased risk of
      mortality in CHD patients, particularly when comorbid with depression. Future
      studies should focus on the co-occurrence of these psychosocial factors as
      markers of increased mortality risk.

PMID- 23537806
TI  - Joint commission primary stroke centers utilize more rt-PA in the nationwide
      inpatient sample.
AB  - BACKGROUND: The Joint Commission began certifying primary stroke centers (PSCs)
      in December 2003 and provides a standardized definition of stroke center care. It
      is unknown if PSCs outperform noncertified hospitals. We hypothesized that PSCs
      would use more recombinant tissue plasminogen activator (rt-PA) for ischemic
      stroke than would non-PSCs. METHODS AND RESULTS: Data were obtained from the
      Nationwide Inpatient Sample from 2004 to 2009. The analysis was limited to states
      that publicly reported hospital identity. All patients >=18 years with a primary
      diagnosis of acute ischemic stroke were included. Subjects were excluded if the
      treating hospital was not identified, if it was not possible to determine the
      temporal relationship between certification and admission, and/or if admitted as
      a transfer. Rt-PA was defined by ICD9 procedure code 99.10. All eligibility
      criteria were met by 323 228 discharges from 26 states. There were 63 145 (19.5%)
      at certified PSCs. Intravenous rt-PA was administered to 3.1% overall: 2.2% at
      non-PSCs and 6.7% at PSCs. Between 2004 and 2009, rt-PA administration increased
      from 1.4% to 3.3% at non-PSCs and from 6.0% to 7.6% at PSCs. In a multivariable
      model incorporating year, age, sex, race, insurance, income, comorbidities, DRG
      based disease severity, and hospital characteristics, evaluation at a PSC was
      significantly associated with rt-PA utilization (OR, 1.87; 95% CI, 1.61 to 2.16).
      CONCLUSIONS: Subjects evaluated at PSCs were more likely to receive rt-PA than
      those evaluated at non-PSCs. This association was significant after adjustment
      for patient and hospital-level variables. Systems of care are necessary to ensure
      stroke patients have rapid access to PSCs throughout the United States.

PMID- 23537807
TI  - Hemoglobin a1c is associated with increased risk of incident coronary heart
      disease among apparently healthy, nondiabetic men and women.
AB  - BACKGROUND: Hemoglobin A1c (HbA1c), a time-integrated marker of glycemic control,
      predicts risk of coronary heart disease (CHD) among diabetics. Few studies have
      examined HbA1c and risk of CHD among women and men without clinically elevated
      levels or previously diagnosed diabetes. METHODS AND RESULTS: We conducted
      parallel nested case-control studies among women (Nurses' Health Study) and men
      (Health Professionals Follow-up Study). During 14 and 10 years of follow-up, 468
      women and 454 men developed incident nonfatal myocardial infarction (MI) and
      fatal CHD. Controls were matched 2:1 based on age, smoking, and date of blood
      draw. For these analyses, participants with a history of diabetes or HbA1c levels
      >=6.5% at baseline were excluded. Compared with HbA1c of 5.0% to <5.5%, those
      with an HbA1c of 6.0% to <6.5% had a multivariable-adjusted relative risk (RR) of
      CHD of 1.90 (95% CI 1.11 to 3.25) in women and 1.81 (95% CI 1.09 to 3.03) in men.
      The pooled RR of CHD was 1.29 (95% CI 1.11 to 1.50) for every 0.5%-increment
      increase in HbA1c levels and 1.67 (95% CI 1.23 to 2.25) for every 1%-increment
      increase, with the risk plateauing around 5.0%. Furthermore, participants with
      HbA1c levels between 6.0% and <6.5% and C-reactive protein levels >3.0 mg/L had a
      2.5-fold higher risk of CHD compared with participants in the lowest categories
      of both biomarkers. CONCLUSIONS: Our findings suggest that HbA1c is associated
      with CHD risk among apparently healthy, nondiabetic women and men and may be an
      important early clinical marker of disease risk.

PMID- 23537809
TI  - Aspirin--another type of headache it prevents.

PMID- 23537808
TI  - Simple risk model predicts incidence of atrial fibrillation in a racially and
      geographically diverse population: the CHARGE-AF consortium.
AB  - BACKGROUND: Tools for the prediction of atrial fibrillation (AF) may identify
      high-risk individuals more likely to benefit from preventive interventions and
      serve as a benchmark to test novel putative risk factors. METHODS AND RESULTS:
      Individual-level data from 3 large cohorts in the United States (Atherosclerosis
      Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the
      Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years
      (19% African Americans, 81% whites) were pooled to derive predictive models for
      AF using clinical variables. Validation of the derived models was performed in
      7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and
      the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the
      derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive
      model including the variables age, race, height, weight, systolic and diastolic
      blood pressure, current smoking, use of antihypertensive medication, diabetes,
      and history of myocardial infarction and heart failure had good discrimination (C
      statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the
      electrocardiogram did not improve the overall model discrimination (C-statistic,
      0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, 
      0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was
      acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic,
      0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. CONCLUSION: A risk
      model including variables readily available in primary care settings adequately
      predicted AF in diverse populations from the United States and Europe.

PMID- 23537810
TI  - Dietary and plasma magnesium and risk of coronary heart disease among women.
AB  - BACKGROUND: Magnesium is associated with lower risk of sudden cardiac death,
      possibly through antiarrhythmic mechanisms. Magnesium influences endothelial
      function, inflammation, blood pressure, and diabetes, but a direct relation with
      coronary heart disease (CHD) risk has not been established. METHODS AND RESULTS:
      We prospectively examined the association between dietary and plasma magnesium
      and risk of CHD among women in the Nurses' Health Study. The association for
      magnesium intake was examined among 86 323 women free of disease in 1980.
      Information on magnesium intake and lifestyle factors was ascertained every 2 to
      4 years through questionnaires. Through 2008, 3614 cases of CHD (2511
      nonfatal/1103 fatal) were documented. For plasma magnesium, we conducted a nested
      case-control analysis, with 458 cases of incident CHD (400 nonfatal/58 fatal)
      matched to controls (1:1) on age, smoking, fasting status, and date of blood
      sampling. Higher magnesium intake was not associated with lower risk of total CHD
      (P-linear trend=0.12) or nonfatal CHD (P-linear trend=0.88) in multivariable
      models. However, magnesium intake was inversely associated with risk of fatal
      CHD. The RR comparing quintile 5 to quintile 1 of magnesium intake was 0.61 (95%
      CI, 0.45 to 0.84; P-linear trend=0.003). The association between magnesium intake
      and risk of fatal CHD appeared to be mediated partially by hypertension. Plasma
      magnesium levels above 2.0 mg/dL were associated with lower risk of CHD, although
      not independent of other cardiovascular biomarkers (RR, 0.67; 95% CI, 0.44 to
      1.04). CONCLUSIONS: Dietary and plasma magnesium were not associated with total
      CHD incidence in this population of women. Dietary magnesium intake was inversely
      associated with fatal CHD, which may be mediated in part by hypertension.

PMID- 23537811
TI  - Tailored Thienopyridine therapy: no urgency for CYP2C19 genotyping.
AB  - Between 20% and 50% of cardiovascular patients treated with clopidogrel, an anti
      P2Y12 drug, display high on-treatment platelet reactivity (HTPR) and are not
      adequately protected from major adverse cardiovascular events (MACE). Despite a
      minor influence of the CYP2C19*2 genetic variant on the pharmacodynamic response
      to clopidogrel (5% to 12%) and a limited or absent value for predicting stent
      thrombosis and MACE, this latter polymorphism is currently considered an
      important candidate to tailor anti-P2Y12 therapy during percutaneous coronary
      intervention. Seven studies have examined the value of CYP2C19*2 for predicting
      HTPR in comparison to a specific pharmacodynamic assay (VASP assay). Overall, the
      summarized sensitivity of the CYP2C19*2 genotype for predicting HTPR was 37.6%
      (95% CI: 32.2 to 43.3%), yielding a negative likelihood ratio of only 0.77 (95%
      CI: 0.68 to 0.86) which confirms its limited value as a routine clinical aid. A
      tailored anti-P2Y12 treatment strategy restricted to CYP2C19*2 carriers may be of
      some help, but this restrictive approach leaves out noncarriers with HTPR. As for
      platelet function testing, there is currently no convincing data to support that
      using CYP2C19*2 genotyping as a tailored anti-P2Y12 treatment would be an
      effective strategy and there is no urgency for CYP2C19 genotyping in clinical
      practice. Strategies incorporating genotyping, phenotyping, and clinical data in
      a stratified and sequential approach may be more promising.

PMID- 23537812
TI  - Long-term outcomes of catheter ablation of atrial fibrillation: a systematic
      review and meta-analysis.
AB  - BACKGROUND: In the past decade, catheter ablation has become an established
      therapy for symptomatic atrial fibrillation (AF). Until very recently, few data
      have been available to guide the clinical community on the outcomes of AF
      ablation at >=3 years of follow-up. We aimed to systematically review the medical
      literature to evaluate the long-term outcomes of AF ablation. METHODS AND
      RESULTS: A structured electronic database search (PubMed, Embase, Web of Science,
      Cochrane) of the scientific literature was performed for studies describing
      outcomes at >=3 years after AF ablation, with a mean follow-up of >=24 months
      after the index procedure. The following data were extracted: (1) single
      procedure success, (2) multiple-procedure success, and (3) requirement for repeat
      procedures. Data were extracted from 19 studies, including 6167 patients
      undergoing AF ablation. Single-procedure freedom from atrial arrhythmia at long
      term follow-up was 53.1% (95% CI 46.2% to 60.0%) overall, 54.1% (95% CI 44.4% to
      63.4%) in paroxysmal AF, and 41.8% (95% CI 25.2% to 60.5%) in nonparoxysmal AF.
      Substantial heterogeneity (I(2)>50%) was noted for single-procedure outcomes.
      With multiple procedures, the long-term success rate was 79.8% (95% CI 75.0% to
      83.8%) overall, with significant heterogeneity (I(2)>50%).The average number of
      procedures per patient was 1.51 (95% CI 1.36 to 1.67). CONCLUSIONS: Catheter
      ablation is an effective and durable long-term therapeutic strategy for some AF
      patients. Although significant heterogeneity is seen with single procedures, long
      term freedom from atrial arrhythmia can be achieved in some patients, but
      multiple procedures may be required.

PMID- 23537813
TI  - Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases
      in cardiac amyloidosis.
AB  - BACKGROUND: Cardiac amyloidosis due to amyloid fibril deposition in the heart
      results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction
      disturbances. Immunoglobulin light chain-related CMP (AL-CMP) features rapidly
      progressive HF with an extremely poor prognosis compared with a CMP due to the
      deposition of mutant (ATTR) amyloidosis or wild-type (senile systemic
      amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition
      disrupts the myocardial extracellular matrix (ECM) homeostasis, which is partly
      regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors
      (TIMPs). We therefore tested the hypothesis that circulating levels of MMPs and
      TIMPs in patients with AL-CMP and TTR-related CMP (TTR-CMP) are dissimilar and
      indicative of cardiac amyloid disease type. METHODS AND RESULTS: Fifty AL-CMP
      patients were compared with 50 TTR-CMP patients (composed of 38 SSA and 12 ATTR
      patients). Clinical and laboratory evaluations including echocardiography were
      performed at the initial visit to our center and analyzed. Serum MMP-2, MMP-9,
      TIMP-1, and TIMP-2 levels were determined by ELISA. Compared with TTR-CMP
      patients, AL-CMP patients had higher levels of brain natriuretic peptide (BNP),
      troponin I (TnI), MMP-2, TIMP-1, and MMP-2/TIMP-2 ratio, despite less left
      ventricular (LV) hypertrophy and better preserved LV ejection fraction. Mortality
      was worse in AL-CMP patients than in TTR-CMP patients (log-rank P<0.01). MMP
      2/TIMP-2 plus BNP and TnI showed the highest discriminative ability for
      distinguishing AL-CMP from TTR-CMP. Female sex (HR, 2.343; P=0.049) and BNP (HR,
      1.041; P<0.01) were predictors for mortality for all patients with cardiac
      amyloidoses. Only BNP was a predictor of death in AL-CMP patients (HR, 1.090;
      P<0.01). There were no prognostic factors for all-cause death in TTR-CMP
      patients. CONCLUSIONS: Circulating concentrations of MMPs and TIMPs may be useful
      in differentiating patients with AL-CMP from those with TTR-CMP, resulting in
      earlier diagnostic vigilance, and may add prognostic information. In addition to
      an elevated BNP level, female sex increased the risk of death in patients with
      cardiac amyloidoses.

PMID- 23537814
TI  - Expanded genetic code for the engineering of ribosomally synthetized and post
      translationally modified peptide natural products (RiPPs).
AB  - The number of constituent amino acids in ribosomally synthetized and post
      translationally modified peptide natural products (RiPPs) is restricted to the 20
      canonical amino acids. Microorganisms with an engineered genetic code are capable
      of delivering the biological, chemical, or physical properties of many unnatural
      or synthetic noncanonical amino acids, ncAAs (in different combinations of their
      numbers and chemistry) precisely defined by the chemist at the bench. In this
      way, post-translational modifications (PTMs) which make RiPPs chemically
      extremely rich can be augmented by the co-translational insertion of ncAAs. This
      will dramatically expand the chemical and functional space of these molecules and
      enable the design of novel and unique sequence combinations with improved
      specificity, stability, membrane permeability and even better oral availability. 

PMID- 23537815
TI  - From the first drop to the first truckload: commercialization of microbial
      processes for renewable chemicals.
AB  - Fermentation of carbohydrate substrates by microorganisms represents an
      attractive route for the manufacture of industrial chemicals from renewable
      resources. The technology to manipulate metabolism of bacteria and yeast,
      including the introduction of heterologous chemical pathways, has accelerated
      research in this field. However, the public literature contains very few examples
      of strains achieving the production metrics required for commercialization. This
      article presents the challenges in reaching commercial titer, yield, and
      productivity targets, along with other necessary strain and process
      characteristics. It then reviews various methods in systems biology, synthetic
      biology, enzyme engineering, and fermentation engineering which can be applied to
      strain improvement, and presents a strategy for using these tools to overcome the
      major hurdles on the path to commercialization. 

PMID- 23537816
TI  - Self-efficacy in adolescents with inflammatory bowel disease: a pilot study of
      the "IBD-yourself", a disease-specific questionnaire.
AB  - BACKGROUND AND AIMS: Successful transfer of adolescent IBD patients to an adult
      gastroenterologist requires anticipation of a changing role for patients and
      their parents. Self-efficacy has been demonstrated to be important for transfer
      readiness. We therefore developed an IBD-specific questionnaire (the "IBD
      yourself") to assess self-efficacy in adolescent IBD patients visiting a
      transition clinic. Our aim was to evaluate the reliability of this questionnaire,
      and to describe the self-efficacy level of adolescent IBD patients, and the
      perceived self-efficacy level according to their parents. METHODS: In a cross
      sectional design, 50 IBD patients (aged 14-18 years) and 40 parents completed the
      "IBD-yourself" questionnaire. Internal reliability was assessed by standardised
      Cronbach's alpha. Median self-efficacy scores per domain were calculated.
      RESULTS: The domains of the questionnaire for adolescents showed good to
      excellent internal consistency, with Cronbach's alpha ranging from 0.64 to 0.93.
      The domains of the parental questionnaire had Cronbach's alpha ranging from 0.47
      to 0.93. Median self-efficacy scores of adolescents varied from 70 to 100%. In
      comparison with patient's self-assessment, parents thought that their child was
      more self-efficacious in knowledge of IBD and diagnostic tests, self-management
      of medication use, and transfer readiness. Length of time since first visit to
      the transition clinic was positively correlated with several domains of the
      questionnaire, such as independent behaviour at the outpatient clinic, and
      transfer readiness. CONCLUSION: The "IBD-yourself" questionnaire is a first step
      toward evaluating quality and efficacy of IBD transition programmes. Paediatric
      gastroenterologists should be aware that parents do not always accurately assess
      the self-efficacy of their child.

PMID- 23537817
TI  - Predictors and safety of venous thromboembolism prophylaxis among hospitalized
      inflammatory bowel disease patients.
AB  - INTRODUCTION: Inflammatory bowel disease (IBD) patients are at increased risk of
      venous thromboembolism (VTE) especially during hospitalization. We assessed the
      safety and predictors of VTE prophylaxis in this population. METHODS: We
      conducted a retrospective study of 974 IBD admissions between February 2010 and
      May 2012. We abstracted data on clinical characteristics, VTE prophylaxis and
      bleeding events, and conducted multivariate analysis to determine predictors of
      prophylaxis. RESULTS: Pharmacological VTE prophylaxis was administered to 80% of
      admissions; 63% were within 24h of admission. Patients on the surgical service
      (adjusted OR [aOR], 3.82; 95% CI: 2.00-7.29) and general medicine (aOR, 2.40; 95%
      CI: 1.39-4.12) were more likely to receive VTE prophylaxis compared to those on
      the gastroenterology service. Rectal bleeding on admission was associated with
      lower prophylaxis (aOR, 0.58; 95% CI: 0.35-0.97). The VTE prophylaxis rate
      increased from 47% to 73% (P<0.001) on non-surgical services with the
      introduction of a pharmacist advocate. The rates of major and minor bleeding were
      similar between patients who did and did not receive VTE prophylaxis (0.26 vs. 0
      per 1000 person-days, P=0.7; 4.18 vs. 2.53 per 1000 person-days, P=0.4
      respectively), and the major bleeding events (n=2) were post-operative. VTE
      prophylaxis was not associated with major postoperative bleeding (0.4% vs. 0%,
      P=0.96). CONCLUSIONS: VTE prophylaxis was more frequent on the surgical service,
      where standardized protocols exist. The introduction of a pharmacist advocate
      greatly increased VTE prophylaxis on the non-surgical services. Prophylactic
      anticoagulation is safe in IBD despite the presence of rectal bleeding on
      admission.

PMID- 23537818
TI  - Public health nursing education in Saudi Arabia.
AB  - Public health nurses are key personnel in promoting and protecting the health of
      populations using knowledge from the nursing, social, and public health sciences.
      In Saudi Arabia, the nursing profession requires the integration of public health
      education and associated competencies in the nursing curriculum. In this paper,
      we aim to highlight the importance of public health nursing in overcoming the
      challenges associated with epidemiological transitions and responding to the
      health needs of rising populations, describe the development of the nursing
      profession in Saudi Arabia, and recommend public health teaching and training
      objectives for nursing education. The future Saudi public health nurse should be
      competent in addressing the determinants of health and illness that are salient
      to a culturally distinct group. This newly outlined role for public health nurses
      will maximize the use of the educated Saudi nursing workforce and will fill the
      gap in population public health needs in an efficient and effective way.

PMID- 23537819
TI  - Evidence for avian H9N2 influenza virus infections among rural villagers in
      Cambodia.
AB  - BACKGROUND: Southeast Asia remains a critical region for the emergence of novel
      and/or zoonotic influenza, underscoring the importance of extensive sampling in
      rural areas where early transmission is most likely to occur. METHODS: In 2008,
      800 adult participants from eight sites were enrolled in a prospective population
      based study of avian influenza (AI) virus transmission where highly pathogenic
      avian influenza (HPAI) H5N1 virus had been reported in humans and poultry from
      2006 to 2008. From their enrollment sera and questionnaires, we report risk
      factor findings for serologic evidence of previous infection with 18 AI virus
      strains. RESULTS: Serologic assays revealed no evidence of previous infection
      with 13 different low-pathogenic AI viruses or with HPAI avian-like
      A/Cambodia/R0404050/2007(H5N1). However, 21 participants had elevated antibodies
      against avian-like A/Hong Kong/1073/1999(H9N2), validated with a monoclonal
      antibody blocking ELISA assay specific for avian H9. CONCLUSIONS: Although cross
      reaction from antibodies against human influenza viruses cannot be completely
      excluded, the study data suggest that a number of participants were previously
      infected with the avian-like A/Hong Kong/1073/1999(H9N2) virus, likely due to as
      yet unidentified environmental exposures. Prospective data from this cohort will
      help us better understand the serology of zoonotic influenza infection in a rural
      cohort in SE Asia.

PMID- 23537820
TI  - Factors associated with influenza vaccination among US children in 2008.
AB  - BACKGROUND: Relative to adults, children have a higher risk of influenza-related
      illnesses, and they play a major role in the spread of infections through a
      household. Because the primary caregiver is responsible for the overall health of
      the child, it is important to analyze the relationship between caregiver
      characteristics and childhood immunizations. This study examined the
      characteristics of the caregiver, household, and child to identify factors
      associated with childhood influenza immunizations. METHODS: Data for children
      aged 19-35 months (n=25,256) were collected from the 2008 National Immunization
      Survey (NIS). The studied caregiver characteristics included age, education
      level, and marital status. Demographic variables included the child's age, sex,
      race/ethnicity, firstborn status, and insurance status in addition to household
      size, region, and poverty status. All analyses were weighted to reflect the
      complex sampling frame of the NIS. RESULTS: Overall, 56.39% of children aged 19
      35 months had received a flu vaccination. Factors associated with an increased
      likelihood of vaccination included the primary caregiver being older, married,
      and more educated and living in the Northeast. A child with private insurance was
      more likely to be immunized than a child with any other type of insurance
      (public: OR 0.6483, 0.5589, 0.7521; no insurance: OR 0.6759, 0.4694, 0.9732).
      Hispanic children (OR 1.1554, 1.0312, 1.2945) were more likely to be vaccinated
      than their counterparts. CONCLUSIONS: Understanding the characteristics related
      to the rates of childhood influenza immunization can help policy makers develop
      and tailor programs to improve immunization education and delivery, especially to
      the groups that are least likely to participate.

PMID- 23537821
TI  - Screening for surgical nosocomial infections by crossing databases.
AB  - Surgical site infection (SSI) is a major cause of morbidity and mortality, and
      they are the third cause of nosocomial infections. It has been shown that
      surveillance can reduce the rate of these infections because the publication of
      the results that introduce a interrogation on her surgical pratices. However,
      surveillance requires considerable medical resources. Our objective is to
      validate a computer algorithm that uses microbiological results and the results
      of a C-reactive protein (CRP) assay and granulocyte count to detect SSIs.
      MATERIALS AND METHODS: All patients who underwent colorectal surgery between the
      1st of January and the 30th of June 2009 were included. Administrative, surgical
      and microbiological data and the appearance of neutrophilia and CRP after surgery
      and during hospitalization were collected. The algorithm uses four biological
      variables: CRP, neutrophils, and the bacterium found on the positive sample. The
      CRP and neutrophil variables were coded in 0 or 1. CRP was coded as 1 if the
      sample was below 5mg/l at the time of the operation and increased to more than
      60mg/l in the 30 days immediately after post-operation. Neutrophils were coded as
      1 if the sample was normal at the time of the operation and increased to more
      than 12,000cells/mm(3) in the 30 days immediately after post-operation. The "type
      of sample" and "bacterium" variables were coded in categories. For the type of
      sample, we coded 3 if the sampling site was related to the surgical site, 2 if
      the sampling site was potentially linked to the surgical site, 1 if the sampling
      site was not directly or indirectly related to the surgical site and 0 if there
      was no sample. Regarding the bacteria, we coded 3 for bacteria found in over 5%
      of SSIs, 2 for bacteria found in 2-5% of SSIs, 1 for bacteria found in less than
      2% of SSIs and 0 if there were no bacteria. The algorithm calculates a score from
      1 to 5. RESULTS: Our study included 195 operations, out of which it was possible
      to study 168. Following the operations, we found neutrophilia above
      12,000cells/mm(3) in 41.5% of cases and CRP above 60mg/l in 64.6% of cases.
      Thirty-seven operations (22%) were complicated by an SSI. The positive predictive
      values and the negative predictive values in our algorithm were 74.07% and
      87.94%, respectively, and the number of records that remain to be investigated is
      27 out of 168. CONCLUSIONS: Linking databases from bacteriology and biology with
      those containing the hospital records of surgical procedures is a simple method
      for identifying surgical nosocomial infections.

PMID- 23537822
TI  - Effectiveness of a multidimensional approach for the prevention of ventilator
      associated pneumonia in an adult intensive care unit in Cuba: findings of the
      International Nosocomial Infection Control Consortium (INICC).
AB  - OBJECTIVE: This study sought to assess the effect of the multidimensional
      approach developed by the International Nosocomial Infection Control Consortium
      (INICC) on the reduction of ventilator-associated pneumonia (VAP) rates in
      patients hospitalized in an adult intensive care unit (AICU) in an INICC member
      hospital in Havana, Cuba. METHODS: We conducted a prospective surveillance pre
      post study in AICU patients. The study was divided into two periods:baseline and
      intervention. During the baseline period, we conducted active prospective
      surveillance of VAP using the Centers for Disease Control and Prevention (CDC)
      National Health Safety Network (NHSN) definition and INICC methods. During the
      intervention period, we implemented the INICC multidimensional approach for VAP,
      in addition to performing active surveillance. This multidimensional approach
      included the following measures: a bundle of infection control interventions,
      education, outcome surveillance, process surveillance, feedback of VAP rates and
      performance feedback of infection control practices. The baseline rates of VAP
      were compared to the rates obtained after intervention, and we analyzed the
      impact of our interventions by Poisson regression. RESULTS: During the baseline
      period, we recorded 114 mechanical ventilator (MV) days, whereas we recorded
      2350MV days during the intervention period. The baseline rate of VAP was 52.63
      per 1000MV days and 15.32 per 1000MV days during the intervention. At the end of
      the study period, we achieved a 70% reduction in the rate of VAP (RR, 0.3; 95%
      CI, 0.12-0.7; P value, 0.003.). CONCLUSIONS: The implementation the INICC
      multidimensional approach for VAP was associated with a significant reduction in
      the VAP rate in the participating AICU of Cuba.

PMID- 23537823
TI  - The detection of ESBL-producing Escherichia coli in patients with symptomatic
      urinary tract infections using different diffusion methods in a rural setting.
AB  - OBJECTIVES: This study aimed to determine the prevalence of extended spectrum of
      beta lactamases (ESBLs), to compare different phenotypic methods for ESBL
      confirmation and to evaluate the antibiotic resistance patterns among ESBL
      producing urinary Escherichia coli. METHODS: Urinary E. coli isolates that were
      resistant to at least one of the three indicator cephalosporins (cefotaxime,
      cefpodoxime and ceftazidime) were tested for ESBL production using the double
      disc synergy test (DDST), the inhibitory potentiated disc diffusion (IPDD) test
      and the quantitative E-strip method. RESULT: Of the 163 E. coli strains isolated,
      80 (49%) were resistant to at least one of the three cephalosporins, and 38
      (47.5%) tested positive for ESBLs by the IPDD test and the E-strip test. However,
      only15 (18.7%) strains tested positive by the DDST. Among the third-generation
      cephalosporins, cefpodoxime (46.1%) was the best screening indicator, followed by
      ceftazidime (43%) and cefotaxime (39.9%). Most of the ESBL producers (97.3%) were
      resistant to three or more drugs, compared with 51.2% of non-ESBL producers.
      CONCLUSION: Compared with the DDST, the IPDD and E-strip tests appear to be
      preferable methods for detecting ESBLs, with better sensitivity (100%) and
      specificilty (97.6%) and positive predictive values (97.3%). ESBL producers
      showed significantly (p<0.05) higher resistance to tobramycin, co-amoxyclav and
      amikacin than did non-ESBL producers.

PMID- 23537824
TI  - Seroprevalence of varicella-zoster virus in the prevaccine era: a population
      based study in Izmir, Turkey.
AB  - PURPOSE: To determine the population-based seroprevalence of varicella zoster
      virus (VZV) and related risk factors in Izmir. MATERIALS AND METHODS: A
      population-based household survey was conducted. A representative sample of the
      population older than 15 years of age was selected using multistage random
      sampling. A total of 2136 healthy persons participated in this cross-sectional
      study. The participants completed a questionnaire designed to collect data
      related to socio-demographic characteristics and risk factors. Blood samples were
      collected, and VZV-specific IgG was measured using an ELISA. RESULTS: In total,
      94.3% of individuals were seropositive for VZV. The difference between VZV
      seroprevalence in urban and rural populations was significant (OR: 2.6 (95% CI,
      1.7-3.8)). No statistically significant differences in seropositivity were
      observed with respect to other sociodemographic characteristics. CONCLUSION: A
      large proportion of the participants were found to be immune to VZV.

PMID- 23537825
TI  - Efficacy of glucantime for treatment of cutaneous leishmaniasis in Central Iran.
AB  - Glucantime remains the first-line treatment for cutaneous leishmaniasis. In a
      prospective study, we evaluated its efficacy and side effects in patients treated
      in Yazd from 2010 to 2011. METHODS: Patients with lesions compatible with
      cutaneous leishmaniasis were considered eligible for inclusion in this study if
      the disease was confirmed parasitologically. The exclusion criteria were as
      follows: the patient preferred a treatment modality other than Glucantime; there
      was no indication for treatment; the patient had underlying kidney, liver, or
      cardiac disease; or was pregnant and lactating. Patients with <=3 lesions and/or
      lesions <3cm in diameter were treated with Glucantime intralesionally if the
      lesions were not located on the face, neck or joints; sporotrichoid; or
      superinfected with bacteria. All other patients were prescribed intramuscular
      Glucantime at 10-20mg/kg/day for 20 days. RESULTS: The failure rate for patients
      treated with one course of Glucantime was 22.6% overall. There were no
      associations between age, sex, weight, the route of administration, the number
      and size of lesions, the adequacy of the dose of the drug injected
      intramuscularly, the number of intralesional injections (<6 or >=6) and the
      duration of therapy. The only factor associated with failure was reported
      previous exposure to antimony (p value 0.047). Adverse effects occurred in 14.2%
      of patients (22/155). CONCLUSION: Glucantime is an effective drug for the
      treatment of cutaneous leishmaniasis in central Iran. However, because cutaneous
      leishmaniasis heals spontaneously and to prevent the acquisition of resistance,
      the indications for treatment in each region should be defined carefully.

PMID- 23537826
TI  - Association between intestinal helminth infections and underweight among school
      children in Tikur Wuha Elementary School, Northwestern Ethiopia.
AB  - BACKGROUND: The association of intestinal helminths with undernutrition varies by
      locality. The objective of this study was to investigate the nature of the
      association of helminth infection with the nutritional status of school children
      in Tikur Wuha Elementary School, northwestern Ethiopia. METHODS: A total of 403
      school children were examined for intestinal helminth infection (stool samples)
      and nutritional status, thick Kato-Katz and anthropometric techniques,
      respectively during a baseline survey. Among these children, 235 were treated for
      helminth infection and re-examined for weight changes four weeks after treatment.
      RESULTS: Among the 403 study participants, 29.3%, 28.3% and 58.3% were stunted,
      underweight and infected with intestinal helminths, respectively. In the
      multivariate regression model, the probability of being underweight was
      significantly higher in children who were infected with intestinal helminths,
      aged 5-10 years and male compared with children who were without helminth
      infection, aged 11-15 years and female, respectively. The association of
      helminths with low body mass was strong in the case of hookworm infection, and
      the probability of being underweight significantly decreased with every one-year
      increase in the age of the children. The means for weight, weight-for-age z
      scores and body mass index-for-age z-scores of the children significantly
      increased four weeks after treatment for helminth infection, with a single dose
      of albendazole and/or praziquantel. CONCLUSIONS: Helminth-infected male children
      in the 5- to 10-year-old age group were more vulnerable to undernutrition, which
      decreased four weeks after treatment. Thus, deworming of children living in the
      area might be important for improving their nutritional status.

PMID- 23537827
TI  - Application of three uniplex polymerase chain reaction assays for the detection
      of atypical bacteria in asthmatic patients in Kuwait.
AB  - BACKGROUND: Respiratory infections are known to exacerbate wheezing in many
      asthmatic patients. We aimed to use molecular methods for the fast detection of
      Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila in
      respiratory specimens from asthmatic patients in Kuwait. METHODS: We used uniplex
      PCR assays to detect the three atypical bacteria in clinical specimens from 235
      asthmatic and non-asthmatic patients in Kuwait. A regression analysis was used to
      identify the risk factors related to the bacterial type. Group comparisons for
      similarity were conducted and correlation coefficients were calculated using SPSS
      statistical software. RESULTS: The detection limits using uniplex PCR for C.
      pneumoniae, L. pneumophila and M. pneumoniae were approximately 1pg, 2.4fg and
      12pg of DNA, respectively. M. pneumoniae PCR positivity was more common in
      asthmatic patients (15%) than in non-asthmatic subjects (9%) (P<0.05). A marked
      difference was observed between patients with acute asthma exacerbation (11%) and
      patients with chronic (stable) asthma (7%) among Kuwaiti patients; these
      percentages were 16% for non-Kuwaiti acute asthma patients and 14% for non
      Kuwaiti chronic asthma patients (P<0.201). There was a weak positive correlation
      between asthma severity and PCR positivity for M. pneumoniae. The PCR results for
      C. pneumoniae and L. pneumoniae were found to be statistically insignificant.
      CONCLUSIONS: The results of this study suggest that infection with M. pneumoniae
      may be related to the exacerbation of asthma symptoms and could possibly be a
      factor that induces wheezing.

PMID- 23537828
TI  - The prevalence of intestinal parasitic infections in the urban slums of a city in
      Western India.
AB  - BACKGROUND: There is scant information available on the prevalence of parasitic
      infections in Gujarat, a state in Western India. The present community-based
      study was undertaken in the urban slums of a city in Gujarat to determine the
      following parameters: (a) the prevalence and type of pathogenic intestinal
      parasites and (b) the availability of sanitary facilities in the study
      population. MATERIALS AND METHODS: This cross-sectional study was conducted in
      2008, and the study participants were urban slum dwellers. Considering an
      expected infection prevalence of 30% among slum dwellers, an allowable error of
      10% and an anticipated design effect of two, the sample size for the cluster
      design was set to 1800 participants from 30 clusters and 360 households (HHs).
      Stool samples were examined using both direct wet mount and the formalin-ether
      sedimentation concentration technique, followed by trichrome staining for
      protozoan cysts. RESULTS: Toilet facilities were utilized by 56% of the HHs,
      while 44% of the HHs resorted to open air defecation. The overall prevalence rate
      of intestinal parasitic infections was 15.19%. Parasitic infections due to
      protozoa were observed in 70.71% of the study participants. Helminth infections
      were detected in 25.71% of the participants, and multiple parasitic infections
      were detected in 3.57%. Diarrhea was the most common complaint (9.56%) in the
      study population. CONCLUSIONS: This study demonstrates that poor sanitation and
      inadequate environmental conditions are the main determining factors that
      predispose the population to intestinal parasites. Mass deworming programs are
      recommended for school children, as this population is easily accessible.

PMID- 23537829
TI  - Origanum vulgare mediated biosynthesis of silver nanoparticles for its
      antibacterial and anticancer activity.
AB  - In the present study, we achieved silver nanoparticles using the aqueous extract
      of Origanum vulgare (Oregano) by reducing 1mM silver nitrate (AgNO3) solution.
      The green synthesized silver nanoparticles were characterized by high throughput
      techniques like UV-vis spectroscopy, Fourier infrared spectroscopy (FT-IR), field
      emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD) and
      dynamic light scattering measurements. Morphologically, the nanoparticles were
      found to be spherical with an average particle size distribution of 136+/
      10.09nm. FT-IR spectral analysis illustrates the occurrence of possible
      biomolecules required for the reduction of silver ions. The obtained
      nanoparticles were stable (-26+/-0.77mV) at ambient temperature. The
      biosynthesized nanoparticles were found to be impressive in inhibiting human
      pathogens. The green synthesized silver nanoparticles showed dose dependent
      response against human lung cancer A549 cell line (LD50 - 100MUg/ml).

PMID- 23537830
TI  - Preparation of Eudragit L 100-55 enteric nanoparticles by a novel emulsion
      diffusion method.
AB  - In this study, a novel emulsion diffusion method was used to prepare enteric
      Eudragit L100-55 nanoparticles by ultrasonic dispersion and diffusion
      solidification. Omeprazole was selected as the model drug. The prepared
      nanoparticles were in spherical shape and exhibited negative zeta potential. The
      Fourier transform infrared spectroscopy results indicated that no molecular
      interaction occurred between the drug molecule and polymer chain. In addition,
      the nanoparticles showed a strong pH-sensitive release in vitro. A mild
      cytotoxicity of nanoparticle was observed in the subsequent studies, and the
      particle cellular uptake study showed that the nanoparticles could be taken up by
      Caco-2 cells after 0.5h incubation. Our results indicated that the enteric
      Eudragit L 100-55 nanoparticle could be synthesized successfully via this
      ultrasonic solidification method, which also could be applied to prepare other pH
      sensitive polymer nanoparticles.

PMID- 23537831
TI  - Orientational behaviors of liquid crystals coupled to chitosan-disrupted
      phospholipid membranes at the aqueous-liquid crystal interface.
AB  - In this study, we investigated the orientational behavior of liquid crystals
      (LCs) which is associated with the chitosan-disrupted phospholipid membrane at
      the aqueous/LC interface. The optical response of LCs changed from dark to bright
      after the transfer of an aqueous solution of chitosan onto the LC interface
      decorated with self-assembled monolayers of a negatively charged phospholipid,
      dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG). The chitosan
      lipid interactions induced a rearrangement of the membrane, and thus, resulted in
      an orientational transition of LCs from a homeotropic to a planar state, thereby
      triggering a dark-to-bright shift in the optical response. We observed that LCs
      exhibited a bright-to-dark shift after an aqueous solution of lysozyme was
      transferred onto the chitosan-disrupted membrane, which implied that an enzymatic
      reaction between lysozyme and chitosan took place. We found that the addition of
      bovine serum album (BSA) induced a bright-to-dark change in the optical response;
      while LCs remained to appear bright after the transfer of chymotrypsin onto the
      aqueous/LC interface. We then further examined the interactions between other
      polyelectrolytes and phospholipid membranes.

PMID- 23537832
TI  - Casein hydrolytic peptides mediated green synthesis of antibacterial silver
      nanoparticles.
AB  - A green route based on the casein hydrolytic peptides (CHPs) has been established
      for the synthesis of highly stable and smaller sized (10+/-5nm) silver
      nanoparticles (AgNPs), without producing any type of toxic byproducts. The
      formation of AgNPs was triggered by the addition of an aqueous NaOH solution due
      to the catalytic properties of OH(-) and/or hydration of the functional groups of
      CHPs. The 99% transformation of Ag ions (9mM) in 20mL reaction mixture into
      identical AgNPs using substantially low concentration of CHPs (0.3%, wt/v),
      indicates that the present system is suitable for the "low volume high
      concentration" nanosynthesis. The AgNPs obtained by CHPs showed the minimum
      inhibitory concentration at 24.5ppm against both gram positive and gram negative
      bacterial cultures with a 96-well titer plate assay. The AgNPs possibly interact
      with the cell wall structures of pathogenic bacteria, Escherichia coli, causing
      changes in the cell morphology and the formation of porous structures, as
      observed by scanning electron microscopy. This eco-friendly process for the bio
      mimetic production of AgNPs is a nontoxic and a competitive alternative to
      existing physical and chemical methods for the production of nano-scale inorganic
      materials.

PMID- 23537833
TI  - A photochemical method for improvement of color stability at polymer-wood
      biointerfaces.
AB  - The possibility of photochemical improvement of color stability by UV-irradiation
      treatment at coating-wood biointerfaces was investigated. The surface of beech
      wood was partially delignified by exposure to UV-irradiation by passing of
      samples under UV lamps: a mercury (Hg) lamp with a peak wavelength of 366nm, a
      gallium (Ga) lamp with peak wavelengths at 410 and 420nm and a combination of a
      mercury and a gallium (Hg+Ga) lamp. After UV-irradiation, the samples were coated
      with a UV-curable acrylic coating. The number of passes under the lamps was
      varied to determine the optimum combination of the number of passes and the lamp
      type that produces the smallest change in color of the coated wood in an indoor
      environment. The coated samples that had been UV-irradiated by passing 15 times
      under both an Hg lamp and a Ga lamp showed the smallest change in color (decrease
      in the DeltaE by 23.23% compared to the untreated coated samples) after 72h of
      accelerated artificial sunlight exposure. Microscope images of the same samples
      showed deformation of the cells in wood surface layer and a roughening of the
      "wood-coating line", which could be related to a partial removal of lignin. These
      findings suggest that delignification of wood leads to more photo-stable polymer
      wood interfaces in terms of color.

PMID- 23537834
TI  - Synthesis of oleic acid functionalized Fe3O4 magnetic nanoparticles and studying
      their interaction with tumor cells for potential hyperthermia applications.
AB  - In the present study, oleic acid (OA) functionalized Fe3O4 magnetic nanoparticles
      (MN) were synthesized following modified wet method of MN synthesis. The optimum
      amount of OA required for capping of MN and the amount of bound and unbound/free
      OA was determined by thermogravimetric analysis (TGA). Further, we have studied
      the effect of water molecules, associated with MN, on the variation in their
      induction heating ability under alternating current (AC) magnetic field
      conditions. We have employed a new approach to achieve dispersion of OA
      functionalized MN (MN-OA) in aqueous medium using sodium carbonate, which
      improves their biological applicability. Interactions amongst MN, OA and sodium
      carbonate were studied by Fourier transform infrared spectroscopy (FT-IR).
      Intracellular localization of MN-OA was studied in mouse fibrosarcoma cells (WEHI
      164) by prussian blue staining and confocal laser scanning microscopy (CLSM)
      using nile blue A as a fluorescent probe. Results showed MN-OA to be interacting
      mainly with the cell membrane. Their hyperthermic killing ability was evaluated
      in WEHI-164 cells by trypan blue method. Cells treated with MN-OA in combination
      with induction heating showed decreased viability as compared to respective
      induction heating controls. These results were supported by altered cellular
      morphology after treatment of MN-OA in combination with induction heating.
      Further, the magnitude of apoptosis was found to be ~5 folds higher in cells
      treated with MN-OA in combination with induction heating as compared to untreated
      control. These results suggest the efficacy of MN-OA in killing of tumor cells by
      cellular hyperthermia.

PMID- 23537835
TI  - Tunable hydrogel-nanoparticles release system for sustained combination therapies
      in the spinal cord.
AB  - Poly(methyl methacrylate) (PMMA) nanoparticles (NPs) were prepared by emulsion
      free radical polymerization. NPs with controlled dimension, as monitored by
      dynamic light scattering (DLS) and transmission electron microscopy (TEM), were
      produced by changing experimental parameters, such as the amount of emulsifier
      and the monomer feeding mode (batch or semi-batch). Then, different sized NPs
      (60, 80 and 130nm) were loaded in polysaccharide-polyacrylic acid based
      hydrogels, cross-linked by covalent ester bonds between polyacrylic acid (PAA)
      and agarose chains, with different pore sizes (30, 60, 90nm). The characteristics
      of the resulting composite hydrogel-NPs system were firstly studied in terms of
      rheological properties and ability to release Rhodamine B that presents steric
      hindrance similar to many neuroprotective agents used in spinal cord injury (SCI)
      repair. Then, diffusion-controlled release of different sized NPs from different
      entangled hydrogels was investigated in vitro and correlated with NPs diameter
      and hydrogel mean mesh size, showing different hindrances to the diffusion
      pathways. Release experiments and diffusion studies, rationalized by mathematical
      modeling and verified in vivo, allowed to build a material library able to
      satisfy different medical drug delivery needs.

PMID- 23537836
TI  - In vivo antitumor activity of biosynthesized silver nanoparticles using Ficus
      religiosa as a nanofactory in DAL induced mice model.
AB  - Ficus religiosa leaf extract was chosen as a reducing agent to fabricate silver
      nanoparticles (AgNPs) by a simple, cost-effective and eco-friendly process with
      the aim of treating Dalton's ascites lymphoma (DAL) in mice model. The formation
      of synthesized nanoparticles were characterized by UV-visible analysis (UV-vis),
      Fourier transform infra-red (FT-IR), transmission electron microscopy (TEM), X
      ray diffraction (XRD) and zeta potential analyses. A peak at 431nm indicated the
      surface plasmon resonance of AgNPs. FTIR studies indicated polyphenols and
      proteins as possible encapsulates. TEM analysis showed particles size in the
      range of 5-35nm. Healthy Swiss Albino mice (30-35g) were intraperitoneally
      induced with DAL cells and treated with F. religiosa derived AgNPs at a dose of
      50MUg/ml. Blood and liver tissues were collected subsequent to dissection and
      subjected to hematological, biochemical and anticancer assays. Hematological and
      biochemical analyses revealed revival after treating with F. religiosa derived
      AgNPs. Antioxidant activity results further proved supportive evidence. The
      apoptosis inducing effect of AgNPs was observed through acridine orange staining
      (AO and EB) and DNA fragmentation assay. Anti- angiogenic activity was confirmed
      by observing vessel development. All these observations indicate that the AgNPs
      were effective in treatment of DAL.

PMID- 23537837
TI  - Effects of ceftriaxone on the acquisition and maintenance of ethanol drinking in
      peri-adolescent and adult female alcohol-preferring (P) rats.
AB  - Increased glutamatergic neurotransmission appears to mediate the reinforcing
      properties of drugs of abuse, including ethanol (EtOH). We recently reported that
      the administration of ceftriaxone (CEF), a beta-lactam antibiotic known to
      upregulate glutamate transporter 1 (GLT1) levels/activity, decreased the
      maintenance of EtOH intake in adult male alcohol-preferring (P) rats. In the
      present study, we tested whether CEF administration would reduce the acquisition
      and maintenance of EtOH drinking in adolescent and adult female P rats. The rats
      were treated with saline or 200mg/kg ceftriaxone for 7 days (starting at 35 or 75
      days old, respectively) followed by the EtOH acquisition test. Five weeks later
      the effects of CEF were examined regarding the maintenance of EtOH intake. For
      the maintenance test, half of the animals that received CEF during acquisition
      received CEF for 7 days and the other half received saline for 7 days. Saline
      treated acquisition animals were treated similarly. The results indicated that
      pretreatment with ceftriaxone reduced the maintenance of EtOH intake in both
      animals that started as adolescents and those that started as adults. However,
      the beneficial effect of CEF was more pronounced in rats pretreated with CEF as
      adults compared with rats pretreated as adolescents. Reductions in EtOH intake by
      ceftriaxone were paralleled by an upregulation of GLT1 protein levels in both the
      nucleus accumbens (~25% in rats starting at both ages) and prefrontal cortex
      (~50% in rats starting as peri-adolescents and ~65% in those starting as adults).
      These findings provide further support for GLT1-associated mechanisms in high
      alcohol-consuming behavior, and hold promise for the development of effective
      treatments targeting alcohol abuse and dependence.

PMID- 23537839
TI  - GABA increases stimulus selectivity of neurons in primary visual cortices of cats
      chronically treated with morphine.
AB  - Chronic exposure to opiates leads to maladaptive changes in various functions of
      the mammalian brain, including properties of neuronal response in the visual
      pathway. In the present study, we used multibarreled microelectrodes to study the
      effects of electrophoretic application of GABA or the GABAA receptor antagonist
      bicuculline on the properties of individual V1 neurons in cats which were
      chronically treated with morphine (MTCs) or saline (STCs). The results showed
      that the application of either GABA or bicuculline significantly altered
      spontaneous activity as well as orientation selectivity and signal-to-noise
      ratios of visually evoked responses in both MTCs and STCs. While administration
      of bicuculline exerted a much stronger effect on neuronal responses of V1 neurons
      of the STCs, administration of GABA resulted in improved visual function mainly
      in MTCs. Most importantly, GABA-treated cells in area V1 of the MTCs displayed
      similar responses to those in STCs. These results are consistent with the idea
      that: (1) there is a decrease in GABA-mediated inhibition in area V1 of cats
      exposed chronically to morphine, and (2) this decrease contributes strongly to
      the apparent degradation of neuronal function observed in animals exposed
      chronically to morphine.

PMID- 23537838
TI  - Neuroanatomical distribution of MU-opioid receptor mRNA and binding in monogamous
      prairie voles (Microtus ochrogaster) and non-monogamous meadow voles (Microtus
      pennsylvanicus).
AB  - The opiate system has long been implicated in the rewarding properties of social
      interactions. In particular, the MU-opioid receptor (MOR) mediates multiple forms
      of social attachment, including the attachment of offspring to the mother and
      social bonding between mates. We have previously shown that MOR in the caudate
      putamen is involved in partner preference formation in monogamous prairie voles.
      Here, using in situ hybridization and receptor autoradiography, we mapped in
      detail the distribution of MOR mRNA and ligand binding in monogamous prairie vole
      brains and compared MOR binding density with that of promiscuous meadow vole
      brains. Comparison of MOR binding in these closely related species with
      distinctly different social behavior revealed that while the distribution of MOR
      is similar, prairie voles have significantly higher densities of MOR than meadow
      voles in a majority of regions in the forebrain, including the caudate-putamen,
      nucleus accumbens shell, lateral septum and several thalamic nuclei, including
      the anteroventral and anteromedial thalamic nuclei. These differences in MOR
      expression between prairie and meadow voles could potentially contribute to
      species differences in behavior, including social attachment.

PMID- 23537840
TI  - First isolation and genetic characterization of a Toxoplasma gondii strain from a
      symptomatic human case of congenital toxoplasmosis in Romania.
AB  - Very limited data exists on the genetic diversity of Toxoplasma gondii from
      Eastern Europe. We present the first Romanian case of symptomatic congenital
      toxoplasmosis in which the T. gondii strain was isolated after inoculation in
      mice of a cerebrospinal fluid sample from a living neonate. The T. gondii strain
      was genotyped with 15 microsatellite markers distributed on 10 of the 14
      chromosomes of T. gondii. The strain had a type II genotype.

PMID- 23537842
TI  - Maternal hyperphenylalaninemia: rapid achievement of metabolic control predicts
      overall control throughout pregnancy.
AB  - Women with hyperphenylalaninemia are at risk of having offspring affected with
      the maternal phenylketonuria syndrome. Here we analyze the effect of the
      intervention of a nutritionist on plasma phenylalanine control in Maternal
      Hyperphenylalaninemia. We analyzed a retrospective cohort of 35 completed
      pregnancies in 20 women with Maternal Hyperphenylalaninemia who visited the
      metabolic nutritionist during the pregnancy to achieve metabolic control. Women
      who promptly achieved metabolic control had lower plasma phenylalanine
      concentrations for the remainder of the pregnancy when compared to women who did
      not achieve prompt control, and this difference reached statistical significance.
      The achievement of plasma phenylalanine concentrations within the desired target
      range by the time of the second visit to the nutritionist is a strong predictor
      of the ability to maintain the desired target range of plasma phenylalanine for
      the remainder of the pregnancy. Furthermore, we demonstrate that phenylalanine
      tolerance increases significantly by trimester in women with classical and
      variant hyperphenylalaninemia.

PMID- 23537843
TI  - Associations of self-esteem, dysfunctional beliefs and coping style with
      depression in patients with schizophrenia: a preliminary survey.
AB  - Psychological models of depression in schizophrenia have proposed that cognitive
      structures (e.g., self-esteem, dysfunctional beliefs) may have a role in the
      development and maintenance of depression. However, it has not been clear what
      the characteristics of these cognitive structures were in people with
      schizophrenia and whether they have an independent association with depression,
      especially in those from a Chinese cultural background. The present investigation
      examined 133 people with schizophrenia and 50 healthy controls and indicated that
      compared to the controls people with schizophrenia showed lower self-esteem,
      higher levels of dysfunctional beliefs and negative coping styles. Multiple
      linear regression analysis revealed that only low frustration tolerance, problem
      solving and self-blame were found to be the independent correlates of depression
      in schizophrenia. Results are discussed with the view of clinical implications of
      cognitive formulation and therapy for schizophrenia in China. 

PMID- 23537841
TI  - The effect of idursulfase on growth in patients with Hunter syndrome: data from
      the Hunter Outcome Survey (HOS).
AB  - Hunter syndrome (mucopolysaccharidosis type II) is a rare and life-limiting
      multisystemic disorder with an X-linked recessive pattern of inheritance. Short
      stature is a prominent feature of this condition. This analysis aimed to
      investigate the effects of enzyme replacement therapy with idursulfase on growth
      in patients enrolled in HOS - the Hunter Outcome Survey which is a multinational
      observational database. As of Jan 2012, height data before treatment were
      available for 567 of 740 males followed prospectively after HOS entry. Cross
      sectional analysis showed that short stature became apparent after approximately
      8 years of age; before this, height remained within the normal range. Age
      corrected standardized height scores (z-scores) before and after treatment were
      assessed using piecewise regression model analysis in 133 patients (8-15 years of
      age at treatment start; data available on >= 1 occasion within +/-24 months of
      treatment start; growth hormone-treated patients excluded). Results showed that
      the slope after treatment (slope=-0.005) was significantly improved compared with
      before treatment (slope=-0.043) (difference=0.038, p=0.004). Analysis of
      covariates (age at treatment start, cognitive involvement, presence of puberty at
      the start of ERT, mutation type, functional classification), showed a significant
      influence on growth of mutation type (height deficit in terms of z-scores most
      pronounced in patients with deletions/large rearrangements/nonsense mutations,
      p<0.0001) and age (most pronounced in the 12-15-year group, p<0.0001). Cognitive
      involvement, pubertal status at the start of ERT and functional classification
      were not related to the growth deficit or response to treatment. In conclusion,
      the data showed an improvement in growth rate in patients with Hunter syndrome
      following idursulfase treatment.

PMID- 23537845
TI  - Situation awareness in obsessive-compulsive disorder.
AB  - Past studies have suggested that OCD patients suffer memory impairment on tasks
      using complex stimuli that require memory for combined elements to be maintained,
      but not for more simplistic memory tests. We tested this with 42 OCD patients and
      42 healthy controls performed a computerized situation awareness task. In
      addition, participants completed the Yale-Brown Obsessive Compulsive Scale (Y
      BOCS) and Maudsley Obsessive-Compulsive Inventory (MOCI). The OCD patients had
      poorer accuracy in integration/comprehension and perception levels than controls.
      There were significant correlations between situational awareness scores (i.e.,
      visuo-spatial monitoring and processing) and Y-BOCS obsession-compulsion and
      slowness and doubt scores of MOCI in OCD patients. In addition, there were also
      significant correlations between situational awareness and controlling, cleaning,
      slowness, rumination and total scores of MOCI in control group. Results indicated
      that (I) OCD patients have problems of perception, integration, and comprehension
      of complex visual perceptions; (II) situation awareness deficits associated with
      severity and prevalence of obsessions and compulsions. 

PMID- 23537844
TI  - Self-assessment of functional ability in schizophrenia: milestone achievement and
      its relationship to accuracy of self-evaluation.
AB  - Between 50% and 80% of patients with schizophrenia do not believe they have any
      illness, and their self-assessment of cognitive impairments and functional
      abilities is also impaired compared to other information, including informant
      reports and scores on performance-based ability measures. The present article
      explores self-assessment accuracy in reference to real world functioning as
      measured by milestone achievement such as employment and independent living. Our
      sample included 195 people with schizophrenia examined with a performance-based
      assessment of neurocognitive abilities and functional capacity. We compared
      patient self-assessments across achievement of milestones, using patient
      performance on cognitive and functional capacity measures as a reference point.
      Performance on measures of functional capacity and cognition was better in people
      who had achieved employment and residential milestones. Patients with current
      employment and independence in residence rated themselves as more capable than
      those who were currently unemployed or not independent. However, individuals who
      had never had a job rated themselves at least as capable as those who had been
      previously employed. These data suggest that lifetime failure to achieve
      functional milestones is associated with overestimation of abilities. As many
      patients with schizophrenia never achieve milestones, their self-assessment may
      be overly optimistic as a result.

PMID- 23537846
TI  - The Spanish validation of an Eating Disorders Symptom Impact Scale (EDSIS) among
      caregivers.
AB  - The aim of this study was to examine the psychometric properties of the Spanish
      version of the Eating Disorders Symptom Impact Scale (EDSIS-S), which is designed
      to evaluate an eating disorders-specific caregiving experience. A cross-sectional
      study was conducted among 187 Spanish caregivers of relatives with an eating
      disorder. Measures included the Experience of Caregiving Inventory (ECI) and
      General Health Questionnaire (GHQ-12). Socio-demographic variables of the carers
      and clinical variables of the patients were collected. Results supported the
      factorial structure, reliability and convergent validity of the instrument and
      the instrument was acceptable for assessing the eating disorders-specific
      experience of caregiving in Spain. Almost all of the factor loadings were >0.40.
      Cronbach's alpha coefficients were mostly superior to 0.70. The EDSIS-S
      instrument has good psychometric properties and is similar to the original in
      terms of validity and reliability. Further examination of the factor structure of
      this instrument among adult samples is indicated. From a clinical perspective,
      the EDSIS allows for tailoring caregiver interventions to address the specific
      impact of symptoms on individual carers. 

PMID- 23537847
TI  - Affinity maturation of a computationally designed binding protein affords a
      functional but disordered polypeptide.
AB  - Computational methods have been recently applied to the design of protein-protein
      interfaces. Using this approach, a 61 amino acid long protein called Spider Roll
      was engineered to recognize the kinase domain of the human p21-activated kinase 1
      (PAK1) with good specificity but modest affinity (KD=100MUM). Here we show that
      this artificial protein can be optimized by yeast surface display and
      fluorescence-activated cell sorting. After three rounds of mutagenesis and
      screening, a diverse set of tighter binding variants was obtained. A
      representative binder, MSR7, has a >10(2)-fold higher affinity for PAK1 when
      displayed on yeast and a 6 to 11-fold advantage when produced free in solution.
      In contrast to the starting Spider Roll protein, however, MSR7 unexpectedly
      exhibits characteristics typical of partially disordered proteins, including
      lower alpha-helical content, non-cooperative thermal denaturation, and NMR data
      showing peak broadening and poor signal dispersion. Although conformational
      disorder is increasingly recognized as an important property of proteins involved
      in cellular signaling and regulation, it is poorly modeled by current
      computational methods. Explicit consideration of structural flexibility may
      improve future protein designs and provide deeper insight into molecular events
      at protein-protein interfaces. 

PMID- 23537848
TI  - Deformed grids for single-particle cryo-electron microscopy of specimens
      exhibiting a preferred orientation.
AB  - For biological samples showing a preferred orientation on the carbon support film
      of an electron microscope (EM) grid, accurate three-dimensional (3D)
      reconstructions by single-particle cryo-EM require data collection in which the
      specimen grids are tilted in the microscope, to obtain adequate numbers of
      particles that cover the high-degree angular distribution. However, image drift
      caused by the electron beam interacting with the cryo specimen becomes severe
      when grids are tilted to high angles (>30 degrees ). We produced deformed grids
      by applying a deliberate mechanical deformation to EM grids containing a thin
      carbon film supported by a thick holey carbon film. We applied cryo-EM using
      deformed grids to the isolated cardiac ryanodine receptor, an ion channel complex
      known to assume a preferred orientation on the carbon support film. These grids
      contained more particles having high Euler angle orientations without the need to
      tilt the specimen grids. Meanwhile, the drifting that was apparent in the images
      was reduced from that typical of images from tilted regular EM grids. This was
      achieved by imaging particles in holes close to the deformed areas, where carbon
      films were locally bent, offering planes of inclination with various angles. The
      deformed grids improve the efficiency and quality of data collection for single
      particle cryo-EM of samples showing a limited range of orientations.

PMID- 23537849
TI  - Self-expandable transcatheter aortic valve implantation for aortic stenosis after
      mitral valve surgery.
AB  - OBJECTIVES: Transcatheter aortic valve implantation has emerged as a valuable
      option to treat patients with symptomatic severe aortic stenosis, who are not
      being considered for surgery because of significant comorbidities. Concerns exist
      over treating patients who have previously undergone mitral valve surgery for
      possible interference between the percutaneous aortic valve and the mitral
      prosthesis or ring. METHODS: At our centre, from May 2008 to December 2012, 172
      patients (76 male) with severe symptomatic aortic stenosis were eligible for
      transcatheter aortic valve implant. Nine patients, affected by severe aortic
      stenosis, had previously undergone mitral valve surgery (4 mono-leaflet, 3
      bileaflet, 1 bioprosthesis, 1 mitral ring); they were considered high-risk
      surgical candidates following joint evaluation by cardiac surgeons and
      cardiologist and had undergone TAVI. RESULTS: Seven patients underwent standard
      femoral retrograde CoreValve((r)) (Medtronic Inc., Minneapolis, USA)
      implantation, two patients underwent a direct aortic implantation through a mini
      thoracotomy. All patients experienced immediate improvement of their haemodynamic
      status. No deformation of the nitinol tubing of the CoreValve, nor distortion or
      malfunction of the mechanical valve or mitral ring, occurred as assessed by
      echographical and fluoroscopic evaluation. No major postoperative complications
      occurred. In all patients , echocardiography indicated normal valve function
      during follow-up. CONCLUSIONS: Our experience confirms the feasibility of
      CoreValve implantation in patients with mechanical mitral valves or mitral
      annuloplasty ring.

PMID- 23537850
TI  - Balancing the benefits and risks of blood transfusions in patients undergoing
      cardiac surgery: a propensity-matched analysis.
AB  - OBJECTIVES: Prior studies have found that cardiac surgery patients receiving
      blood transfusions are at risk for increased mortality and morbidity following
      surgery. It is not clear whether this increased risk occurs across all
      haematocrit (HCT) levels. The goal of this study was to compare operative
      mortality in propensity-matched cardiac surgery patients based on stratification
      of the preoperative HCT levels. METHODS: Between 1 August 2004 and 30 June 2011,
      3516 patients had cardiac surgery. One thousand nine hundred and twenty-two
      (54.5%) required blood transfusion during or after surgery. A propensity score
      for transfusion was developed based on 22 baseline variables. One thousand seven
      hundred and fourteen patients were matched: 857 in the transfusion group (TG) and
      857 in the non-transfused control group (CG). Univariate analyses demonstrated
      that, after propensity matching, the groups did not differ on any baseline
      factors included in the propensity model. Operative mortality was defined as
      death within 30 days of surgery. Preoperative HCT was stratified into four
      groups: <36, 36-39, 40-42 and >= 43. RESULTS: For HCT <36%, 30-day mortality was
      higher in the TG than that in the CG (3.0 vs 0.0%). For HCT 36-39, operative
      mortality was similar between TG (1.1%, N = 180) and CG (0.8%, N = 361; P =
      0.748). For HCT 40-42, operative mortality was significantly higher in the TG
      compared with that in the CG (1.9 vs 0%, N = 108 and 218, respectively; P =
      0.044). For HCT of >= 43, there was a trend towards higher operative mortality in
      the TG vs the CG (2.0 vs 0%, N = 102 and 152, respectively; P = 0.083). Other
      surgical complications followed the same pattern with higher rates found in the
      transfused group at higher presurgery HCT levels. HCT at discharge for the eight
      groups were similar, with an average of 29.1 +/- 1.1% (P = 0.117). CONCLUSIONS:
      Our study indicates that a broad application of blood products shows no
      discernible benefits. Furthermore, patients who receive blood at all HCT levels
      may be placed at an increased risk of operative mortality and/or other surgical
      complications. Paradoxically, even though patients with low HCTs theoretically
      should benefit the most, transfusion was still associated with a higher
      complication and mortality rate in these patients. Our results indicate that
      blood transfusion should be used judiciously in cardiac surgery patients.

PMID- 23537851
TI  - Physician eye contact and elder patient perceptions of understanding and
      adherence.
AB  - OBJECTIVE: To Examine physician eye contact (EC), patient understanding and
      adherence. METHODS: Secondary analysis of National Institute of Aging videotapes
      (N=52) of physician-elder patients in two visit types: (1) routine (n=20); (2)
      anxiety-provoking (n=32) was conducted. Self-reports of understanding and
      adherence were used. History-taking segments were qualitatively and
      quantitatively analyzed for relationships between EC, understanding and
      adherence. RESULTS: Qualitative analysis showed: (1) two salient EC elements-
      frequency, type (brief or sustained)--and verbal synchronicity were commonly
      invoked; (2) conjoint unfolding of three communication elements--"looking,
      listening and talking"--may be salient for patient outcomes; (3) despite
      differing EC patterns in routine and anxiety provoking visits, statistical
      analyses showed patient understanding and adherence ratings were similar in the
      sample population comprising two visit types; no significant correlations between
      EC elements and understanding and adherence were found. CONCLUSIONS: Salience of
      EC for patient-centered communication is shown in prior research. Present
      findings broaden the significance of EC by including verbal synchronicity.
      Methodological limitations may account for no significant correlations between EC
      and patient outcomes. PRACTICE IMPLICATIONS: Using suggested framework for
      operationalizing EC elements, including verbally synchronous communication, may
      facilitate patient-centeredness and have positive implications for patient
      understanding and adherence.

PMID- 23537852
TI  - [Can the advertising and food industries help prevent childhood obesity and
      promote healthy lifestyles?].

PMID- 23537853
TI  - Application of the Putting Women First protocol in a study on violence against
      immigrant women in Spain.
AB  - In this paper, we describe our experience of using the Putting Women First
      protocol in the design and implementation of a cross-sectional study on violence
      against women (VAW) among 1607 immigrant women from Morocco, Ecuador and Romania
      living in Spain in 2011. The Putting Women First protocol is an ethical guideline
      for VAW research, which includes recommendations to ensure the safety of the
      women involved in studies on this subject. The response rate in this study was
      59.3%. The prevalence of VAW cases last year was 11.7%, of which 15.6%
      corresponded to Ecuadorian women, 10.9% to Moroccan women and 8.6% to Romanian
      women. We consider that the most important goal for future research is the use of
      VAW scales validated in different languages, which would help to overcome the
      language barriers encountered in this study. 

PMID- 23537854
TI  - [Evolution of knowledge and oral hygiene habits in primary schoolchildren].
AB  - OBJECTIVE: To analyze the evolution of knowledge and habits to oral hygiene
      children and adolescents in Palencia (Spain). METHODS: A descriptive study of
      trend. The population of students from grade 5 of primary education between
      2001/11 of the Palencia. Questionnaire data are collected knowledge and habits of
      the Oral Health Program, which are analyzed descriptively. RESULTS: The trend has
      been improving knowledge until 2006/07, after stagnating (p <0.05). In habits,
      increase students declare brushing teeth three times a day (p <0.05). There is a
      decrease in the consumption of candies between hours from 2004/2005, from 50,3%
      to 38,2% in 2010/11. DISCUSSION: The results of the program seem to be positive.
      Increasing knowledge and improving habits related to oral health health they
      stimulate to continuing being employed at this line.

PMID- 23537855
TI  - [Chlorine concentrations in the air of indoor swimming pools and their effects on
      swimming pool workers].
AB  - OBJECTIVE: To describe chlorine levels in the air of indoor swimming pools in
      Castilla-La Mancha (Spain) and relate them to other chemical parameters in the
      installation and to the health problems perceived by swimming pool workers.
      METHODS: We analyzed 21 pools with chlorine as chemical treatment in Castilla-La
      Mancha. The iodometry method was applied to measure chlorine concentrations in
      the air. The concentrations of free and combined chlorine in water, pH and
      temperature were also evaluated. Health problems were surveyed in 230 swimming
      pool workers in these facilities. RESULTS: The mean chlorine level in the air of
      swimming pools was 4.3 +/- 2.3mg/m(3). The pH values were within the legal
      limits. The temperature parameters did not comply with regulations in 17 of the
      21 pools analyzed. In the pools where chlorine values in the air were above the
      legal regulations, a significantly higher percentage of swimming pool workers
      perceived eye irritation, dryness and irritation of skin, and ear problems.
      CONCLUSIONS: Chlorine values in the air of indoor swimming pools were higher than
      those reported in similar studies. Most of the facilities (85%) exceeded the
      concentration of 1.5mg/m(3) established as the limit for the risk of irritating
      effects. The concentration of chlorine in indoor swimming pool air has a direct
      effect on the self-perceived health problems of swimming pool workers.

PMID- 23537856
TI  - [Profile of the patient who requests a voluntary interruption of pregnancy].

PMID- 23537857
TI  - [Analysis of inequalities in mortality in small areas: obstacles to overcome].
AB  - No analyses have been performed in the Balearic Islands (Spain) to assess health
      inequalities in mortality in small areas. The objective of this study was to
      construct a mortality atlas using geocoding of mortality records. During this
      process, several problems were encountered, which are summarized in this article.
      These problems were based on the lack of stable small geographical areas,
      difficulties in obtaining the population for small areas divided by age and sex
      for the study period, problems with the quality of the cartography, and the poor
      quality of the mortality records. The methodological problems identified in this
      process should be considered in future studies. 

PMID- 23537858
TI  - Recent developments in the genetics of autism spectrum disorders.
AB  - The last several years have marked a turning point in the genetics of autism
      spectrum disorder (ASD) due to rapidly advancing genomic technologies. As the
      pool of bona fide risk genes and regions accumulates, several key themes have
      emerged: these include the important role of rare and de novo mutation, the
      biological overlap among so-called syndromic and 'idiopathic' ASD, the elusive
      nature of the common variant contribution to risk, and the observation that the
      tremendous locus heterogeneity underlying ASD appears to converge on a relatively
      small number of key biological processes. Perhaps most striking has been the
      revelation that ASD mutations show tremendous phenotypic variability ranging from
      social disability to schizophrenia, intellectual disability, language impairment,
      epilepsy and typical development. 

PMID- 23537859
TI  - Association between HIV infection and amniotic fluid index at advanced gestation.

PMID- 23537860
TI  - Mucosal immunity in the gut: the non-vertebrate perspective.
AB  - Much is now known about the vertebrate mechanisms involved in mucosal immunity,
      and the requirement of commensal microbiota at mucosal surfaces for the proper
      functioning of the immune system. In comparison, very little is known about the
      mechanisms of immunity at the barrier epithelia of non-vertebrate organisms. The
      purpose of this review is to summarize key experimental evidence illustrating how
      non-vertebrate immune mechanisms at barrier epithelia compare to those of higher
      vertebrates, using the gut as a model organ. Not only effector mechanisms of gut
      immunity are similar between vertebrates and non-vertebrates, but it also seems
      that the proper functioning of non-vertebrate gut defense mechanisms requires the
      presence of a resident microbiota. As more information becomes available, it will
      be possible to obtain a more accurate picture of how mucosal immunity has
      evolved, and how it adapts to the organisms' life styles.

PMID- 23537862
TI  - The role of angiopoietin-2 in progressive renal fibrosis.

PMID- 23537861
TI  - Targeting the trimolecular complex.
AB  - Class II major histocompatibility molecules (MHC) confer disease risk for
      multiple autoimmune disorders including type 1 diabetes. The interaction between
      the components of the trimolecular complex (CD4(+) T cell receptors, self
      peptide, and MHC class II molecules) plays a pivotal role in autoimmune disease
      pathogenesis. The development of therapies targeting various components of the
      trimolecular complex for the prevention of type 1 diabetes is actively being
      pursued. This review focuses on the components of the anti-insulin trimolecular
      complex, registers of insulin peptide binding to 'diabetogenic' MHC class II
      molecules, and therapies targeting each component of the trimolecular complex. 

PMID- 23537864
TI  - Pharmacokinetics of desflurane elimination from respiratory gas and blood during
      the 20 minutes after cardiac surgery.
AB  - BACKGROUND/PURPOSE: Desflurane, with a low blood-gas partition coefficient, is an
      ideal anesthetic to achieve rapid offset and recovery from general anesthesia.
      Investigation of desflurane elimination from blood and respiratory gas should
      provide useful information with respect to a patient's recovery from anesthesia.
      Therefore, this study is designed to characterize the pharmacokinetics of
      desflurane elimination after cardiac surgery. METHODS: Sixteen patients
      undergoing coronary artery bypass graft surgery were enrolled. At the end of
      surgery, multiple gas and blood samples were taken in the 20 minutes before and
      after stopping desflurane administration, with prior maintenance of a fixed 7%
      inspired desflurane in 6 L/minute oxygen flow for 60 minutes before the
      cessation. The blood desflurane concentrations, including internal jugular-bulb
      blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) were
      analyzed using gas chromatography. The inspiratory desflurane concentration
      (CIdes) and end-tidal desflurane (CEdes) were measured with an infrared analyzer,
      and cardiac output was measured using an Opti-Q pulmonary artery catheter.
      RESULTS: Before cessation of desflurane administration, the inspiratory
      desflurane concentration (CIdes) was relatively higher than end-tidal (CEdes),
      arterial (Ades), internal jugular-bulb blood (Jdes), and pulmonary (PAdes)
      concentrations in sequence (CIdes > CEdes > Ades~ Jdes > PAdes). During the
      elimination phase, rapid decay occurred in CEdes, followed by Jdes, Ades and
      PAdes. Twenty minutes after stopping desflurane administration, the desflurane
      concentrations were: PAdes > Ades~ Jdes > CEdes. The decay curves of desflurane
      concentrations demonstrated two distinct elimination components: an initial, fast
      5-minute component followed by a slow 15-minute component. CONCLUSION: Desflurane
      is eliminated fastest from the lungs, as indicated by CEdes, compared to
      elimination from circulating blood. The initial, rapid 5-minute desflurane
      washout reflected the diluting effect of functional residual capacity of the
      lungs.

PMID- 23537863
TI  - Persistent pulmonary hypertension of the newborn.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is a severe pulmonary
      disorder which occurs at a rate of one in every 500 live births. About 10-50% of
      the victims will die of the problem and 7-20% of the survivors develop long-term
      impairments such as hearing deficit, chronic lung disease, and intracranial
      bleed. Most adult survivors show evidence of augmented pulmonary vasoreactivity,
      suggesting a phenotypical change. Several animal models have been used to study
      the pathophysiology and help to develop new therapeutic modality for PPHN. The
      etiology of PPHN can be classified into three groups: (1) abnormally constricted
      pulmonary vasculature as a result of parenchymal diseases; (2) hypoplastic
      pulmonary vasculature; and (3) normal parenchyma with remodeled pulmonary
      vasculature. Impaired vasorelaxation of pulmonary artery and reduced blood vessel
      density in lungs are two characteristic findings in PPHN. Medical treatment
      includes sedation, oxygen, mechanical ventilation, vasorelaxants (inhaled nitric
      oxide, inhaled or intravenous prostacyclin, intravenous prostaglandin E1,
      magnesium sulfate), and inotropic agents. Phosphodiesterase inhibitors have
      recently been studied as another therapeutic agent for PPHN. Endothelin-1 (ET-1)
      inhibitors have been studied in animals and a case of premature infant with PPHN
      successfully treated with an ET-I inhibitor has been reported in the literature.
      Surfactants have been reported as an adjunct treatment for PPHN as a complication
      of meconium aspiration syndrome. Even with the introduction of several new
      therapeutic modalities there has been no significant change in survival rate.
      Extracorporeal membrane oxygenator is used when medical treatment fails and the
      patient is considered to have a recoverable cause of PPHN.

PMID- 23537865
TI  - Assessment of an automatic robotic arm for dispensing of chemotherapy in a 2500
      bed medical center.
AB  - BACKGROUND/PURPOSE: Automation has long been awaited in parenteral drug
      dispensing. Pharmacists can benefit much in theory from a good automated device
      to handle the hazardous drugs used in chemotherapy. This paper describes the
      performance of the first chemotherapy-dispensing robot in the oncology pharmacy
      of a 2500-bed medical center. The objective of this paper is two-fold: (1) to
      assess the robot's performance in terms of its success rate and to summarize the
      causes of failure, and (2) to find out if the robot can decrease the full-time
      equivalents (FTEs) of the oncology pharmacy. METHODS: We used the computer
      generated log from the first week of May 2010 to that of July 2010, supplemented
      with the pharmacists' notes on the causes of failure, to determine the success
      rate and to analyze the incidences of failure. We also assessed the FTEs before
      and after implementing the robot. RESULTS: Data showed that the success rate rose
      slowly from 76.8% to 95.3% over the 2-month recording period. The major
      mechanical problems encountered were air, clamping, and waste bin problems.
      Manual errors, such as loading wrong drugs or syringes, also caused failures. In
      terms of manpower saving, CytoCare failed to decrease the number of FTE
      pharmacists/technicians in our oncology pharmacy practice. CONCLUSION: We
      conclude that even though CytoCare could ease the risk of chemotherapy exposure
      and increase the precision of dosing, it was not able to improve the FTE
      pharmacists/technicians in our hospital.

PMID- 23537866
TI  - Milder clinical manifestation of scrub typhus in Kinmen, Taiwan.
AB  - BACKGROUND/PURPOSE: Kinmen, an offshore island of Taiwan, is a popular location
      for sightseeing and an important entry port between Taiwan and China. Kinmen is
      also highly endemic for scrub typhus. The authors aimed to investigate the
      disease characteristics there, which remained largely unknown. METHODS: The
      authors conducted a retrospective study on patients with scrub typhus in Kinmen
      during 2005-2008. The clinical information was reviewed from medical records for
      statistical analysis. RESULTS: There were 261 patients with scrub typhus included
      with a bimodal summer-autumn type of distribution, with most patients (40%) age
      20-29 years and a large proportion of patients (26%) older than 60 years. The
      disease manifestation, laboratory examinations, and treatment outcomes were
      comparable in summer and autumn. Fever (97%), eschar (93%), and relative
      bradycardia (67%) were the most common presentations, whereas lymphadenopathy
      (18%) and skin rash (8%) were infrequent. Elevated liver function, C-reactive
      protein levels, and low to normal platelet counts were frequent findings. A
      correct diagnosis was made made in an average 3.7 days after fever or 1.6 visits
      of medical consultation, and minocycline was prescribed in a timely manner. Most
      patients had good recovery and only 12 patients (5%) had severe infection with
      acute renal failure, shock, gastrointestinal bleeding, or respiratory failure; no
      mortality was found. Older age, longer fever duration, thrombocytopenia, abnormal
      liver and renal function, hyponatremia, and elevated C-reactive protein levels
      were significantly associated with severe complications and prolonged treatment
      duration. CONCLUSION: A unique summer-autumn type of scrub typhus with milder
      disease manifestations is identified in Kinmen. The younger patient population,
      rapid diagnosis, and prompt treatment may be associated with a shortened disease
      course and lead to a better outcome.

PMID- 23537867
TI  - Psychopathology, rehospitalization and quality of life among patients with
      schizophrenia under home care case management in Taiwan.
AB  - BACKGROUND/PURPOSE: To study the outcome of a group of patients with
      schizophrenia receiving community home care case management programs by
      delineating the relationship among their psychopathology, rehospitalization rates
      and health-related quality of life (HRQoL). METHODS: This is a cross-sectional
      study on HRQoL, functioning and associating factors and a retrospectivehistorical
      control study by comparing the frequency and duration of rehospitalization in a
      sample of 60 patients with schizophrenia under nonintensive case management (non
      ICM) in Taiwan. All participants were assessed on the Positive and Negative
      Syndrome Scale for Schizophrenia (PANSS) for psychopathology, on EuroQoL-5D (EQ
      5D) and EQ visual analogue (EQ-VAS) for HRQoL, andGlobal Assessment of
      Functioning (GAF) for socio-occupational dysfunction. Other clinical
      characteristics are also gathered. RESULTS: Patients with schizophrenia treated
      with non-ICM had a significant reduction in admission frequency (-0.10 +/- 0.36
      times per year, p = 0.042) and length of inpatient stay (-27.8 +/- 78.0 days per
      year, p = 0.008). Better EQ-5D and EQ-VAS are significantly associated with lower
      general psychopathology score, while better EQ-VAS is significantly associated
      with older age and higher negative symptoms subscale score. GAF is negatively
      associated with higher positive symptoms and negative symptoms subscale scores,
      while positively correlated with a greater reduction in number and frequency of
      admission. CONCLUSION: Non-ICM can help to decrease rehospitalization of home
      care patients. HRQoL and functioning can be assessed by the three perspectives we
      used, and each measure was correlated to different dimensions of patient
      psychopathology. It will be better if we include baseline and post-intervention
      PANSS scores, HRQoL and functioning as outcome indicators.

PMID- 23537868
TI  - Prompt healing of erosive oral lichen planus lesion after combined corticosteroid
      treatment with locally injected triamcinolone acetonide plus oral prednisolone.
AB  - BACKGROUND/PURPOSE: Erosive oral lichen planus (EOLP) is a T-cell-mediated
      inflammatory disease that is refractory to treat. This study tested whether local
      injection of triamcinolone acetonide plus oral administration of low- or medium
      dose prednisolone could hasten the healing of EOLP lesions. METHODS: In this
      study, 50 EOLP patients were treated with local injection of Kenacort A (40 mg
      triamcinolone acetonide once weekly for 3 and 2 weeks for 30 major and 20 minor
      EOLP patients, respectively) plus oral administration of prednisolone (25-30 mg
      and 15-20mg of prednisolone once daily for 2 weeks for 30 major and 20 minor EOLP
      patients, respectively). The oral administration of prednisolone was tapered to
      5mg per day and stopped in 7 days. Then, the patients were treated with topical
      Dexaltin (0.1% dexamethasone, once or twice per daily) and oral administration of
      vitamin Bc (one capsule twice daily) thereafter. RESULTS: After 3-week
      treatments, the 30 major EOLP patients showed complete response (lack of
      detectable erosive or ulcerative lesion with absence or regression of reticular
      or papular OLP) in 27 cases (90%) and partial response (reduction of erosive or
      ulcerative lesion by at least 30% in diameter with regression of reticular or
      papular OLP) in cases (10%); and 20 minor EOLP patients demonstrated complete
      response in 18 cases (90%) and partial response in two cases (10%). However, all
      the 45 complete response major or minor EOLP patients showed recurrence of
      erosive or ulcerative lesion after 3-24 (mean 12) months of follow-up.
      CONCLUSION: Prompt and complete healing of the EOLP lesions could be achieved in
      a relative short period of time after treatment with our protocol. Although
      complete response EOLP lesions recurred after a follow-up period of 3-24 months,
      patients did have an average remission period of 12 months after treatment with
      our protocol.

PMID- 23537869
TI  - A pharmaco-economic evaluation of deferasirox for treating patients with iron
      overload caused by transfusion-dependent thalassemia in Taiwan.
AB  - BACKGROUND/PURPOSE: The newly available iron chelator deferasirox (Exjade,
      Novartis) is expected to provide better long-term clinical outcomes and improved
      quality of life for patients with thalassemia than its predecessor, deferoxamine
      (Desferal, Novartis), because of its oral tablet form. METHODS: We used the
      Markov model to estimate total additional lifetime costs and quality-adjusted
      life years (QALYs) gained with deferasirox versus deferoxamine in patients with
      transfusion-dependent thalassemia. Patients were assumed to be 2 years of age at
      initiation of chelation therapy. Clinical outcomes in terms of morbidity and
      mortality from associated complications and life expectancy for the study
      population were estimated using the databases of the Bureau of National Health
      Insurance and the Health and Vital Statistics of Taiwan. Treatment costs were
      based on analyses of health insurance claims for patients with transfusion
      dependent thalassemia. Utilities in terms of quality of life were also included
      in the model. The incremental cost-utility ratio of deferasirox versus
      deferoxamine was defined by the ratio of the difference in expected lifetime
      costs to the difference in QALYs. One-way sensitivity analyses were performed to
      examine the robustness of the results to key assumptions. RESULTS: Patients
      treated with deferasirox are expected to experience a lower incidence of
      associated complications and obtain 2.3 QALYs (discounted) at an additional
      lifetime cost of US$36,291 per patient (US$15,596 per QALY). Sensitivity analyses
      showed that the unit drug cost of deferasirox had the greatest impact on the
      incremental cost-utility ratio. In addition, the incremental cost-utility ratio
      will increase by delaying the starting age (2 years of age in our study) of
      chelation therapy. CONCLUSION: Compared with infusional deferoxamine, oral
      deferasirox improved clinical outcomes and quality of life in terms of iron
      chelation in transfusion-dependent patients with thalassemia at a reasonable cost
      from a healthcare perspective.

PMID- 23537870
TI  - Breakthrough Streptococcus pneumoniae type 6B infection after adrenocorticotropic
      hormone therapy in a child vaccinated with pneumococcal conjugate vaccine.
AB  - Despite proven good efficacy of pneumococcal conjugated vaccine in preventing
      invasive pneumococcal disease, breakthrough infections remain a noticeable
      problem with significant morbidity and mortality, especially in selected high
      risk groups. We present a 2-year-old girl with infantile spasm, who was treated
      with antiepileptic drugs and adrenocorticotropic hormone (ACTH). Vaccination with
      three doses 7-valent pneumococcal conjugate vaccine had been completed one month
      before ACTH therapy. Two months after ACTH therapy, she suffered from fever,
      cough, and decreased activity. Streptococcus pneumoniae, serotype 6B, was
      detected in blood culture. Vaccine failure could be possibly due to ACTH therapy.

PMID- 23537871
TI  - Clinical significance of Mycobacterium avium complex isolates at a medical center
      in northern Taiwan.

PMID- 23537872
TI  - Effect of buffer systems and disaccharides concentration on Podoviridae coliphage
      stability during freeze drying and storage.
AB  - The aims of this study were to determine the stability of Podoviridae coliphage
      CA933P during lyophilization and storage in different media, and to establish
      similarities between the results obtained and those expected through mechanisms
      described for proteins stabilization during freeze-drying. PBS and SM buffer were
      assayed as lyophilization media. The effect of inorganic salts concentration as
      well as the addition of disaccharides on phage stability during freeze-drying and
      storage was also studied. The addition of low sucrose concentration (0.1 mol l-1)
      to SM buffer stabilized phage during freezing and drying steps of the
      lyophilization process, but higher sugar concentrations were detrimental to phage
      stability during freeze-drying. Sucrose stabilized phage during storage for at
      least 120 days. The lyoprotective effect of low concentrations of disaccharides
      during the drying step of the lyophilization of proteins as well as the
      stabilization of the freeze-dried product in time correlated with the results
      obtained for phage CA933P.

PMID- 23537873
TI  - A family of small tyrosine rich proteins is essential for oogonial and oospore
      cell wall development of the mycoparasitic oomycete Pythium oligandrum.
AB  - The mycoparasitic oomycete Pythium oligandrum is homothallic, producing an
      abundance of thick-walled spiny oospores in culture. After mining a cDNA sequence
      dataset, we identified a family of genes that code for small tyrosine rich
      (Pythium oligandrumsmall tyrosine rich (PoStr)) proteins. Sequence analysis
      identified similarity between the PoStr proteins and putative glycine-rich cell
      wall proteins from the related plant pathogenic oomycete Pythium ultimum, and
      mating-induced genes from the oomycete Phytophthora infestans. Expression
      analysis showed that PoStr transcripts accumulate during oospore production in
      culture and immunolocalisation indicates the presence of these proteins in
      oogonial and oospore cell walls. PoStr protein abundance correlated positively
      with production of oogonia as determined by antibiotic-mediated oogonia
      suppression. To further characterise the role of PoStr proteins in P. oligandrum
      oospore production, we silenced this gene family using homology-dependent gene
      silencing. This represents the first characterisation of genes using gene
      silencing in a Pythium species. Oospores from silenced strains displayed major
      ultrastructural changes and were sensitive to degradative enzyme treatment.
      Oogonia of silenced strains either appeared to be arrested at the mature oosphere
      stage of development or in around 40 % of the structures, showed a complete
      suppression of oospore formation. Suppressed oogonia were highly vacuolated and
      the oogonium wall was thickened by a new inner wall layer. Our data suggest PoStr
      proteins are probably integral structural components of the normal oospore cell
      wall and play a key role in oospore formation.

PMID- 23537874
TI  - A novel serine protease with caspase- and legumain-like activities from edible
      basidiomycete Flammulina velutipes.
AB  - A serine protease with caspase- and legumain-like activities from basidiocarps of
      the edible basidiomycete Flammulina velutipes was characterized. The protease was
      purified to near homogeneity by three steps of chromatography using acetyl-Tyr
      Val-Ala-Asp-4-methylcoumaryl-7-amide (Ac-YVAD-MCA) as a substrate. The enzyme was
      termed FvSerP (F. velutipes serine protease). This enzyme activity was completely
      inhibited by the caspase-specific inhibitor, Ac-YVAD-CHO, as well as moderately
      inhibited by serine protease inhibitors. Based on the N-terminal sequence, the
      cDNA of FvSerP was identified. The deduced protease sequence was a peptide
      composed of 325 amino acids with a molecular mass of 34.5 kDa. The amino acid
      sequence of FvSerP showed similarity to neither caspases nor to the plant
      subtilisin-like serine protease with caspase-like activity called saspase. FvSerP
      shared identity to the functionally unknown genes from class of Agaricomycetes,
      with similarity to the peptidase S41 domain of a serine protease. It was thus
      concluded that this enzyme is likely a novel serine protease with caspase- and
      legumain-like activities belonging to the peptidase S41 family and distributed in
      the class Agaricomycetes. This enzyme possibly functions in autolysis, a type of
      programmed cell death that occurs in the later stages of development of
      basidiocarps with reference to their enzymatic functions.

PMID- 23537875
TI  - Endophyte communities vary in the needles of Norway spruce clones.
AB  - Endophytic fungi show no symptoms of their presence but can influence the
      performance and vitality of host trees. The potential use of endophytes to
      indicate vitality has been previously realized, but a standard protocol has yet
      to be developed due to an incomplete understanding of the factors that regulate
      endophyte communities. Using a culture-free molecular approach, we examined the
      extent to which host genotype influences the abundance, species richness, and
      community composition of endophytic fungi in Norway spruce needles. Briefly,
      total DNA was extracted from the surface-sterilized needles of 30 clones grown in
      a nursery field and the copy number of the fungal internal transcribed spacer
      (ITS) region of ribosomal DNA was estimated by quantitative PCR. Fungal species
      richness and community composition were determined by denaturing gradient gel
      electrophoresis and DNA sequencing. We found that community structure and ITS
      copy number varied among spruce clones, whereas species richness did not. Host
      traits interacting with endophyte communities included needle surface area and
      the location of cuttings in the experimental area. Although Lophodermium piceae
      is considered the dominant needle endophyte of Norway spruce, we detected this
      species in only 33% of samples. The most frequently observed fungus (66%) was the
      potentially pathogenic Phoma herbarum. Interestingly, ITS copy number of
      endophytic fungi correlated negatively with the richness of ectomycorrhizal fungi
      and thus potential interactions between fungal communities and their influence on
      the host tree are discussed. Our results suggest that in addition to
      environmental factors, endophyte communities of spruce needles are determined by
      host tree identity and needle surface area.

PMID- 23537876
TI  - A comparison of fungal endophytic community diversity in tree leaves of rural and
      urban temperate forests of Kanto district, eastern Japan.
AB  - To clarify the effects of forest fragmentation and a change in tree species
      composition following urbanization on endophytic fungal communities, we isolated
      fungal endophytes from the foliage of nine tree species in suburban (Kashiwa
      City, Chiba) and rural (Mt. Wagakuni, Ibaraki; Mt. Takao, Tokyo) forests and
      compared the fungal communities between sites and host tree species. Host
      specificity was evaluated using the index of host specificity (Si), and the
      number of isolated species, total isolation frequency, and the diversity index
      were calculated. From just one to several host-specific species were recognized
      in all host tree species at all sites. The total isolation frequency of all
      fungal species on Quercus myrsinaefolia, Quercus serrata, and Chamaecyparis
      obtusa and the total isolation frequency of host-specific species on Q.
      myrsinaefolia, Q. serrata, and Eurya japonica were significantly lower in Kashiwa
      than in the rural forests. The similarity indices (nonmetric multidimensional
      scaling (NMS) and CMH) of endophytic communities among different tree species
      were higher in Kashiwa, as many tree species shared the same fungal species in
      the suburban forest. Endophytic fungi with a broad host range were grouped into
      four clusters suggesting their preference for conifer/broadleaves and
      evergreen/deciduous trees. Forest fragmentation and isolation by urbanization
      have been shown to cause the decline of host-specific fungal species and a
      decrease in beta diversity of endophytic communities, i.e., endophytic
      communities associated with tree leaves in suburban forests were found to be
      depauperate.

PMID- 23537877
TI  - Comparative bioluminescence dynamics among multiple Armillaria gallica, A.
      mellea, and A. tabescens genets.
AB  - Bioluminescence is well known among white-spored species of Basidiomycota
      including several species of the white-rot wood decay genus Armillaria. Previous
      work demonstrated consistent differences among A. gallica, A. mellea, and A.
      tabescens in luminescence magnitude and in luminescence expression relative to
      environmental stimuli. In the present studies, temporal fluctuations in mycelial
      luminescence were quantitatively characterized using genets matched for
      geographical location. All genets derived from rhizomorphs or basdiomata were
      constitutively luminescent while six of 13 genets originating from mycelial fans
      were inconsistently luminescent. Using time series of 1000 consecutive
      measurements over 800 ms intervals, fluctuation patterns had significantly
      quantifiable structure and were not simply 'white noise'. Fluctuation patterns
      were qualitatively similar with alternating periods of rapid fluctuation and
      relative stability, regardless of luminescence magnitude. Anomalous spikes or
      shifts in luminescence were recorded for several genets suggesting further work
      to identify the transient stimuli which elicited these altered luminescence
      patterns.

PMID- 23537878
TI  - Culture condition-dependent metabolite profiling of Aspergillus fumigatus with
      antifungal activity.
AB  - Three sections of Aspergillus (five species, 21 strains) were classified
      according to culture medium-dependent and time-dependent secondary metabolite
      profile-based chemotaxonomy. Secondary metabolites were analysed by liquid
      chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS-MS)
      and multivariate statistical methods. From the Aspergillus sections that were
      cultured on malt extract agar (MEA) and Czapek yeast extract agar (CYA) for 7,
      12, and 16 d, Aspergillus sections Fumigati (A. fumigatus), Nigri (A. niger), and
      Flavi (A. flavus, A. oryzae, and A. sojae) clustered separately on the basis of
      the results of the secondary metabolite analyses at 16 d regardless of culture
      medium. Based on orthogonal projection to latent structures discriminant analysis
      by partial least squares discriminant analysis (PLS-DA), we identified the
      secondary metabolites that helped differentiate sections between A. fumigatus and
      Aspergillus section Flavi to be gliotoxin G, fumigatin oxide, fumigatin,
      pseurotin A or D, fumiquinazoline D, fumagillin, helvolic acid, 1,2
      dihydrohelvolic acid, and 5,8-dihydroxy-9,12-octadecadienoic acid (5,8-diHODE).
      Among these compounds, fumagillin, helvolic acid, and 1,2-dihydrohelvolic acid of
      A. fumigatus showed antifungal activities against Malassezia furfur, which is
      lipophilic yeast that causes epidermal skin disorders.

PMID- 23537879
TI  - Ethanol production from high cellulose concentration by the basidiomycete fungus
      Flammulina velutipes.
AB  - Ethanol production by Flammulina velutipes from high substrate concentrations was
      evaluated. F. velutipes produces approximately 40-60 g l(-1) ethanol from 15%
      (w/v) D-glucose, D-fructose, D-mannose, sucrose, maltose, and cellobiose, with
      the highest conversion rate of 83% observed using cellobiose as a carbon source.
      We also attempted to assess direct ethanol fermentation from sugarcane bagasse
      cellulose (SCBC) by F. velutipes. The hydrolysis rate of 15% (w/v) SCBC with
      commercial cellulase was approximately 20%. In contrast, F. velutipes was able to
      produce a significant amount of ethanol from 15% SCBC with the production of beta
      glucosidase, cellobohydrolase, and cellulase, although the addition of a small
      amount of commercial cellulase to the culture was required for the conversion.
      When 9 mg g(-1) biomass of commercial cellulase was added to cultures, 0.36 g of
      ethanol was produced from 1 g of cellulose, corresponding to an ethanol
      conversion rate of 69.6%. These results indicate that F. velutipes would be
      useful for consolidated bioprocessing of lignocellulosic biomass to bioethanol.

PMID- 23537880
TI  - Rapid detection of exon 2-deleted AIMP2 mutation as a potential biomarker for
      lung cancer by molecular beacons.
AB  - Exon 2 deletion in aminoacyl tRNA synthetase complex-interacting multifunctional
      protein 2 (AIMP2) has been suggested to be associated with the progression of
      various cancers such as lung and ovarian cancers. However, few studies have been
      conducted regarding detection and relevance of exon 2-deleted AIMP2 (AIMP2-DX2)
      mutation to a specific cancer. Here, we demonstrate the rapid and simple
      detection of the AIMP2-DX2 mutation by molecular beacons and its relation to lung
      cancer. Real-time PCR with molecular beacons allowed a sensitive detection of the
      AIMP2-DX2 mutation as low as 0.3 pg initial template. Dual-conjugated liposomes
      with folate and molecular beacon enabled fluorescence imaging of cancer cells
      harboring the AIMP2-DX2 mutation with high resolution. Association of the AIMP2
      DX2 mutation with lung cancer was shown by analyzing tissue samples from lung
      cancer patients using real-time PCR. Approximately, 60% of lung cancer patients
      harbored the AIMP2-DX2 mutation, which implies a potential of the AIMP2-DX2
      mutation as a prognostic biomarker for lung cancer. Molecular beacon-based
      approaches will find applications in the simple and rapid detection of mutations
      on nucleotides for diagnosing and monitoring the progression of relevant cancer.

PMID- 23537881
TI  - Direct access and patient/client self-referral to physiotherapy: a review of
      contemporary practice within the European Union.
AB  - BACKGROUND: Direct access refers to service users being able to refer themselves
      to physiotherapy without a third-party referral. It represents a model of
      practice supported globally by the profession, growing research evidence and
      health policy in some health systems. To the authors' knowledge, no research has
      been reported to ascertain the extent to which direct access is available within
      the physiotherapy profession within the European Union (EU). OBJECTIVES: To
      survey member organisations of the World Confederation for Physical Therapy
      (WCPT); establish the number of member states within the EU where it is possible
      for individuals seeking physiotherapy services to self-refer; describe the
      legislative/regulatory and reimbursement contexts in which physiotherapy services
      are delivered; examine if physiotherapy practice is different in member states
      where direct access is permitted compared with member states where direct access
      is not permitted; and to describe the barriers and facilitators to direct access
      perceived by member organisations of the WCPT. DESIGN: Cross-sectional, online
      survey using a purposive sample. PARTICIPANTS: Member organisations of the WCPT
      in the EU. RESULTS: Direct access is not available in all member states of the
      EU, despite the majority having legislation to regulate the profession, and entry
      level education programmes that produce graduates with the requisite
      competencies. Key barriers perceived are those that can influence policy
      development, including the views of the medical profession and politicians.
      Support of service users and politicians, as well as professional autonomy, are
      seen as key facilitators. CONCLUSION: These results represent the first report of
      a comprehensive mapping of direct access to physiotherapy and contexts within the
      EU. In over half of member states, service users can self-refer to
      physiotherapists. These results provide insights to further individuals'
      understanding about the similarities and differences in working practices and
      service delivery factors, such as reimbursement across and within EU member
      states. The synergies between barriers and facilitators indicate the importance
      of targeted advocacy strategies in the introduction of direct access/self
      referral to physiotherapy.

PMID- 23537882
TI  - Recruitment to clinical trials of exercise: challenges in the peripheral arterial
      disease population.
AB  - OBJECTIVES: To describe recruitment to a randomised controlled trial of a 12-week
      (twice-weekly) supervised exercise programme for patients with peripheral
      arterial disease (PAD). PAD is a chronic, progressive disease with a significant
      cardiovascular and cerebrovascular risk burden, and exercise is an effective
      primary management approach. METHOD: Potential patients were identified from the
      Non-Invasive Vascular Laboratory records and invited to participate in the study.
      On successful completion of an incremental treadmill exercise test, patients were
      allocated at random to a control (usual care) or an exercise group. RESULTS:
      Between November 2006 and June 2009, 548 patients were identified. Of the 156
      patients who met the inclusion criteria, 40 (26%) declined to participate. Of the
      71 patients who underwent exercise testing, 23 (32%) did not complete the test.
      The final enrolment number was 44 (44/156; 28%). Eleven patients (11/28; 39%)
      subsequently withdrew from the exercise programme. CONCLUSION: Recruitment to
      clinical trials of exercise presents significant challenges in the PAD population
      due to the presence of co-existing cardiovascular and cerebrovascular disease, a
      reluctance to exercise due to leg pain, and an acceptance of reduced mobility as
      part of ageing. Early identification in primary care before the onset of
      significant comorbidity may ameliorate some of these issues.

PMID- 23537883
TI  - 'Isn't it all Whites?' Ethnic diversity and the physiotherapy profession.
AB  - AIM: To explore physiotherapists' perceptions, views and experiences of ethnic
      diversity in relation to the physiotherapy profession. DESIGN: Qualitative
      research study, drawing on ethnographic traditions and including ethnographic
      interviews. The interviews were transcribed verbatim and the data were analysed
      using thematic analysis. Several verification procedures were incorporated into
      the design to ensure quality. SETTING: Venues chosen by the participants in North
      West England. PARTICIPANTS: A purposive sample of 22 physiotherapists (five
      students, seven clinicians and 10 academics) with a range of ethnicities.
      FINDINGS: Most participants' experiences and perceptions were of a lack of ethnic
      diversity within the profession. Further findings related to the impact of this
      included: the perception that physiotherapy is a White profession; some Black and
      Minority Ethnic (BME) physiotherapists felt 'out of place' on occasions; and
      failure to meet patients' needs. The potential benefits of increased ethnic
      diversity and the possible risks of valuing BME staff solely in terms of their
      ethnicity were also illuminated by the findings. CONCLUSIONS: This study of the
      perceptions and experiences of physiotherapists identified a lack of ethnic
      diversity within the profession. It is argued that a lack of ethnic diversity may
      result in a failure to meet patients' needs. A workforce that is reflective of
      the population it serves can have greater cultural knowledge, and is more likely
      to understand and respond to patients' needs.

PMID- 23537884
TI  - Underestimation of dose delivery in preclinical irradiation due to scattering
      conditions.
AB  - The aim of this study was to evaluate, by comparing simulation results with
      measurement results, the impact of the lack of scattering volume in experimental
      conditions of preclinical irradiation. First, a Monte Carlo model of a small
      animal irradiator, the Faxitron CP-160, was developed with GATE (Geant4
      Application for Tomography Emission). To validate the model, simulated data were
      compared to depth dose and off-axis ratio profiles measured with a plane-parallel
      ionization chamber and Gafchromic((r)) EBT films, respectively, in a solid water
      phantom. The AAPM TG-61 protocol was applied to measure the dose rate at the
      surface of a semi-infinite reference phantom. Then, the model was used to
      determine the dose distributions in three different phantom settings: a semi
      infinite water phantom, a 2.8-cm-thick water phantom and a 2.8-cm-diameter
      cylindrical water phantom. The dose distributions measured and simulated with
      Monte Carlo methods in a semi-infinite water phantom were similar (<2%), thus
      validating our Monte Carlo model. The highest dose underestimation was observed
      between the reference and the cylindrical phantom (more than 15% difference for
      the entrance dose) and was due to the lack of lateral scatter and backscatter.
      The use of standard backscatter factors and AAPM TG-61 protocol may result in a
      significant underestimation of the dose absorbed by small irradiated phantoms,
      such as mice or cells, in preclinical studies. BACKGROUND: For preclinical
      radiotherapy studies, radiobiologists were used to determine the irradiation time
      depending only on the source surface distance. This work aimed to demonstrate
      that scatter conditions have a large impact on dose rate. Measurements and Monte
      Carlo simulations were used.

PMID- 23537885
TI  - Mapping energetics of atom probe evaporation events through first principles
      calculations.
AB  - The purpose of this work is to use atomistic modeling to determine accurate
      inputs into the atom probe tomography (APT) reconstruction process. One of these
      inputs is evaporation field; however, a challenge occurs because single ions and
      dimers have different evaporation fields. We have calculated the evaporation
      field of Al and Sc ions and Al-Al and Al-Sc dimers from an L12-Al3Sc surface
      using ab initio calculations and with a high electric field applied to the
      surface. The evaporation field is defined as the electric field at which the
      energy barrier size is calculated as zero, corresponding to the minimum field
      that atoms from the surface can break their bonds and evaporate from the surface.
      The evaporation field of the surface atoms are ranked from least to greatest as:
      Al-Al dimer, Al ion, Sc ion, and Al-Sc dimer. The first principles results were
      compared with experimental data in the form of an ion evaporation map, which maps
      multi-ion evaporations. From the ion evaporation map of L12-Al3Sc, we extract
      relative evaporation fields and identify that an Al-Al dimer has a lower
      evaporation field than an Al-Sc dimer. Additionally, comparatively an Al-Al
      surface dimer is more likely to evaporate as a dimer, while an Al-Sc surface
      dimer is more likely to evaporate as single ions. These conclusions from the
      experiment agree with the ab initio calculations, validating the use of this
      approach for modeling APT energetics.

PMID- 23537886
TI  - Combined nano-SIMS/AFM/EBSD analysis and atom probe tomography, of carbon
      distribution in austenite/epsilon-martensite high-Mn steels.
AB  - We introduce a new experimental approach for the identification of the atomistic
      position of interstitial carbon in a high-Mn binary alloy consisting of austenite
      and epsilon-martensite. Using combined nano-beam secondary ion mass spectroscopy,
      atomic force microscopy and electron backscatter diffraction analyses, we clearly
      observe carbon partitioning to austenite. Nano-beam secondary ion mass
      spectroscopy and atom probe tomography studies also reveal carbon trapping at
      crystal imperfections as identified by transmission electron microscopy. Three
      main trapping sites can be distinguished: phase boundaries between austenite and
      epsilon-martensite, stacking faults in austenite, and prior austenite grain
      boundaries. Our findings suggest that segregation and/or partitioning of carbon
      can contribute to the austenite-to-martensite transformation of the investigated
      alloy. 

PMID- 23537887
TI  - The maternal autoimmune environment affects the social behavior of offspring.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders with unknown
      etiology. BTBR-T(+)tf/J (BTBR) mice, a mouse strain with behaviors that resemble
      autism and with elevated levels of anti-brain antibodies (Abs), have enhanced
      activation of peripheral B cells and CD4(+) T cells and an expanded percentage of
      CD4(+) T cells expressing Vbeta6 chains. The CD4(+)CD25(+)Vbeta6(+) and Vbeta6
      splenic cells of BTBR mice have elevated levels of IL-4, IFN-gamma and IL-17, but
      there appears to be no preferential CD4(+) T subset skewing/polarization. The
      high level of IgG production by BTBR B cells was dependent on T cells from BTBR
      mice. The CD4(+) T cells of BTBR mice, especially those expressing Vbeta6 become
      spontaneously activated and expanded in an autoimmune-like manner, which occurred
      in both BTBR and B6 hosts that received an equal number of BTBR and B6 bone
      marrow cells. BTBR mice also have an elevated percentage of peripheral blood
      neutrophils, which may represent their elevated inflammatory state. B6 offspring
      derived from B6 dams that were gestationally injected with purified IgG from sera
      of BTBR mice, but not IgG of B6 mice, developed significantly impaired social
      behavior. Additionally, B6 offspring that developed in BTBR dams had impaired
      social behavior, while BTBR offspring that developed in B6 dams had improved
      social behavior. All of the immunological and behavioral parameters of BTBR mice
      were compared with those of B6 mice, which have relatively normal behaviors. The
      results indicate maternal Abs and possibly other maternal influences affect the
      social behavior of offspring.

PMID- 23537888
TI  - Invariant Natural Killer T-cell anergy to endogenous myelin acetyl-glycolipids in
      multiple sclerosis.
AB  - To extend our studies on glycolipid-reactive invariant Natural Killer T-cell
      (iNKT-cell) function in multiple sclerosis (MS), we investigated the stimulatory
      activities of two myelin-derived glycolipids that are poly-acetylated derivatives
      of beta-galactosylceramide designated as fast-migrating cerebrosides (FMC) by
      thin-layer chromatography. In healthy subjects, FMC stimulation of peripheral
      blood cells significantly expanded iNKT-cells similar to alpha-GalCer and induced
      significant increases in Th1, Th2 and Th17 cytokines. In marked contrast, MS
      patients failed to respond to FMCs or to alpha-GalCer stimulation indicating an
      anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT
      cell responses in vivo and this is blocked in MS.

PMID- 23537890
TI  - The involvement of heme oxygenase 1 but not nitric oxide synthase 2 in a
      hepatoprotective action of quercetin in lipopolysaccharide-induced hepatotoxicity
      of D-galactosamine sensitized rats.
AB  - The objective of this study was to evaluate potential hepatoprotective
      capabilities of quercetin in relation to its modulation of the HO-1 and NOS-2
      activities in an experimental model of fulminant liver failure. Liver insult was
      induced by in vivo administration of D-galactosamine (d-GalN, 400 mg/kg, i.p.)
      and lipopolysaccharide (LPS, 10 MUg/kg, i.p.). The effects of quercetin (50
      mg/kg, i.p) on D-GalN toxicity was evaluated by standard biochemical, RT-PCR and
      Western blot methods. Administration of d-GalN/LPS combination resulted in
      significantly higher plasma levels of aminotransferases, as well as increased
      mRNA and protein expressions of both HO-1 and NOS-2 enzymes. Quercetin exhibited
      cytoprotective effects on the liver, as evidenced by decreased aminotransferase
      plasma levels. Additionally, quercetin treatment in D-GalN/LPS treated rats
      significantly increased HO-1 mRNA and its protein expressions. On the contrary,
      quercetin did not exhibit any significant effects on the levels of nitrites, and
      NOS-2 mRNA and protein expressions in D-GalN/LPS treated rats. Quercetin when
      given alone did not have any significant changes on liver enzymes nor HO-1 and
      NOS-2 mRNA and protein expressions. It can be concluded that the quercetin's
      induction of HO-1 and its byproducts, without concomitant NOS-2 activity
      reduction, is among mechanisms contributing to the hepatoprotective effect in D
      GalN/LPS hepatotoxicity.

PMID- 23537889
TI  - Two new tryptophan derivatives from the seed kernels of Entada rheedei: effects
      on cell viability and HIV infectivity.
AB  - Two new tryptophan derivatives, N-sulfonyl-L-tryptophan (tryptorheedei A) (1) and
      3-(N-sulfonylindolyl)-D-lactic acid (tryptorheedei B) (2) together with the known
      5-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid (3), 1-O
      methylglucopyranoside, entadamide A, homogentisic acid and 3-O-beta-D
      glucopyranosyl-beta-sitosterol, were isolated from the seed kernels of Entada
      rheedei (Mimosaceae). Their structures were established using 1D and 2D NMR
      spectroscopy, mass spectrometry and by comparison with spectroscopic data
      reported in the literature. Compounds 1 and 2 showed no toxicity to TZM and Human
      PBMC cells. Both compounds 1 and 2 were found to promote early infection events
      in HIV, likely by inhibiting the enzyme indolamine 2,3-dioxygenase (IDO) and
      preventing tryptophan depletion. Inhibition of IDO acutely in HIV infection
      inhibits viral replication, but chronic activation of IDO leads to immune
      impairment in AIDS. IDO is also the gatekeeper enzyme for kynurenine metabolism,
      a pathway involved in serotonin and melatonin biosynthesis and the regulation of
      glutamate and dopamine levels in the brain. Therefore inhibition of IDO might
      explain both the reported medicinal and neuropsychiatric effects of E. rheedei.

PMID- 23537891
TI  - Associations of aortic distensibility and arterial elasticity with long-term
      visit-to-visit blood pressure variability: the Multi-Ethnic Study of
      Atherosclerosis (MESA).
AB  - BACKGROUND: Although higher visit-to-visit variability (VVV) of blood pressure
      (BP) is associated with increased cardiovascular disease risk, the physiological
      basis for VVV of BP is incompletely understood. METHODS: We examined the
      associations of aortic distensibility (assessed by magnetic resonance imaging)
      and artery elasticity indices (determined by radial artery pulse contour
      analysis) with VVV of BP in 2,640 and 4,560 participants, respectively, from the
      Multi-Ethnic Study of Atherosclerosis. Arterial measures were obtained at exam 1.
      BP readings were taken at exam 1 and at 3 follow-up visits at 18-month intervals
      (exams 2, 3, and 4). VVV was defined as the SD about each participant's mean
      systolic BP (SBP) across visits. RESULTS: The mean SDs of SBP were inversely
      associated with aortic distensibility: 7.7, 9.9, 10.9, and 13.2mm Hg for
      quartiles 4, 3, 2, and 1 of aortic distensibility, respectively (P trend <
      0.001). This association remained significant after adjustment for demographics,
      cardiovascular risk factors, mean SBP, and antihypertensive medication use (P
      trend < 0.01). In a fully adjusted model, lower quartiles of large artery and
      small artery elasticity (LAE and SAE) indices were also associated with higher
      mean SD of SBP (P trend = 0.02 for LAE; P trend < 0.001 for SAE). CONCLUSIONS: In
      this multiethnic cohort, functional alterations of central and peripheral
      arteries were associated with greater long-term VVV of SBP.

PMID- 23537892
TI  - Left ventricular responses to acute changes in late systolic pressure
      augmentation in older adults.
AB  - BACKGROUND: Changes in the cardiovascular system with age may predispose older
      persons to development of heart failure with preserved ejection fraction.
      Vascular stiffening, aortic pressure augmentation, and ventricular-vascular
      coupling have been implicated. We explored the potential for acute reductions in
      late systolic pressure augmentation to impact left ventricular relaxation in
      older persons without heart failure. METHODS: Sixteen older persons free of known
      cardiovascular disease with the exception of hypertension had noninvasive
      tonometry and cardiac ultrasound to evaluate central augmentation index (AI) and
      diastolic function at baseline and after randomized, blinded administration of
      intravenous B-type natriuretic peptide (BNP) and hydralazine in a crossover
      design. RESULTS: AI was significantly reduced after BNP (11.4+/-8.9 to -0.2+/
      14.7%; P = 0.02) and nonsignificantly reduced after hydralazine (14.7+/-8.4% to
      11.5+/-8.8%; P = 0.39). With decreased AI during BNP, a trend toward worsened
      myocardial relaxation by tissue Doppler imaging occurred (E' velocity pre- and
      post-BNP: 10.0+/-2.5 and 8.8+/-2.0cm/s, respectively; P = 0.06). There was a
      significant fall in stroke volume with BNP (68.5+/-18.3 to 60.9+/-18.1ml; P =
      0.02), suggesting that changes in preload overwhelmed effects of afterload
      reduction on ventricular performance. With hydralazine, neither relaxation nor
      stroke volume changed. CONCLUSIONS: Acute changes in late systolic aortic
      pressure augmentation do not necessarily lead to improved systolic or diastolic
      function in older people. Preload may be a more important determinant of cardiac
      performance than afterload in older people with compensated ventricular function.
      The potential for changes in preload to impair rather than enhance left
      ventricular systolic and diastolic function in older people warrants further
      study. CLINICAL TRIALS REGISTRATION: This study is registered at
      clinicaltrials.gov as NCT00204984.

PMID- 23537893
TI  - Patients with type 2 diabetes show a greater decline in muscle mass, muscle
      strength, and functional capacity with aging.
AB  - BACKGROUND: The loss of muscle mass with aging reduces muscle strength, impairs
      functional capacity, and increases the risk of developing chronic metabolic
      disease. It has been suggested that the development of type 2 diabetes results in
      a more rapid decline in muscle mass, strength, and functional capacity.
      OBJECTIVE: To investigate the impact of type 2 diabetes on muscle mass, strength,
      and functional capacity in an older population. METHODS: Muscle mass (DXA and
      muscle biopsies), strength (1-repetition maximum), functional capacity (sit-to
      stand test and handgrip strength), and reaction time performance (computer task)
      were compared between 60 older men with type 2 diabetes (71 +/- 1 years) and 32
      age-matched normoglycemic controls (70 +/- 1 years). Data were analyzed using
      ANCOVA to adjust for several potential confounders. RESULTS: Leg lean mass and
      appendicular skeletal muscle mass were significantly lower in older men with type
      2 diabetes (19.1 +/- 0.3 and 25.9 +/- 0.4 kg, respectively) compared with
      normoglycemic controls (19.7 +/- 0.3 and 26.7 +/- 0.5 kg, respectively).
      Additionally, leg extension strength was significantly lower in the group with
      type 2 diabetes (84 +/- 2 vs 91 +/- 2 kg, respectively). In agreement, functional
      performance was impaired in the men with type 2 diabetes, with longer sit-to
      stand time (9.1 +/- 0.4 vs 7.8 +/- 0.3 seconds) and lower handgrip strength (39.5
      +/- 5.8 vs 44.6 +/- 6.1 kg) when compared with normoglycemic controls. However,
      muscle fiber size and reaction time performance did not differ between groups.
      CONCLUSION: Older patients with type 2 diabetes show an accelerated decline in
      leg lean mass, muscle strength, and functional capacity when compared with
      normoglycemic controls. Exercise intervention programs should be individualized
      to specifically target muscle mass, strength, and functional capacity in the
      older population with type 2 diabetes.

PMID- 23537894
TI  - Antibiogram of urinary isolates.

PMID- 23537895
TI  - Effects of prone and supine positioning on gastric residuals in preterm infants:
      a time series with cross-over study.
AB  - BACKGROUND: Few studies have examined the effect of body position on gastric
      residuals at different time points in feeding preterm infants. Further, the
      results of previous studies are inconsistent. OBJECTIVES: To describe the
      changing pattern of gastric residuals over time in the prone and supine position
      and to examine the effects of position on gastric residuals at different feeding
      volumes in preterm infants. DESIGN: A randomized, time series with cross-over
      study. SETTING: A neonatal intensive care unit affiliated with a medical center
      in central Taiwan. PARTICIPANTS: 35 preterm infants who were asymptomatic for
      gastroesophageal reflux, other gastrointestinal diseases or other significant
      morbidities of any kind other than prematurity. METHODS: Infants were randomly
      assigned to the following treatments: 3h in a supine position followed by 3h in a
      prone position, or vice versa. Measurements of gastric residual volume were taken
      by syringe at 30, 60, 90, 120 and 150 min following feeding when the enteral
      intake was set at 50 or 100ml/kg/day. RESULTS: The rate of decrease of gastric
      residuals in the prone and supine positions was fastest during the first half an
      hour post-feeding according to measurements taken at 30, 60, 90, 120 and 150 min
      at feeding volumes of 50 and 100ml/kg/day (p<001). Gastric residuals were
      significantly lower in the prone than in the supine position at the five
      measurement points. CONCLUSIONS: Placing preterm infants in the prone position
      for the first half an hour post-feeding and then changing the position according
      to the behavior cues of the infants is suggested. This result contributes to a
      better understanding of the relationships between time, position, and gastric
      residuals; it could also help health care professionals to provide efficient
      feeding as well as perform the appropriate positioning of preterm infants.

PMID- 23537896
TI  - [Glucocorticoid therapy: what is the information sought by patients? Traffic
      analysis of the website cortisone-info.fr].
AB  - INTRODUCTION: About 1% of the general population are receiving systemic
      glucocorticoids. The information about this treatment sought by patients is
      unknown. MATERIALS AND METHODS: The website www.cortisone-info.fr aims to provide
      therapeutic information about glucocorticoids and glucocorticoid therapy. It was
      posted on January 16, 2012. The information available on the website is
      documented and based on the recent medical literature. The website is made of 43
      pages divided into five main sections (generalities about glucocorticoids,
      adverse events, measures associated with glucocorticoid therapy, discontinuation
      of glucocorticoids and, situations requiring attention). The website traffic
      between February 1st, 2012 and January 4, 2013 was analyzed using Google
      Analytics. RESULTS: During the study period, the website was visited by 67,496
      people (average number of visitors per day: 33 in February 2012, 326 in December
      2012). The number of page views was 230,496 or an average of 3.5 pages per
      visitor. Of these 230,496 page views, 145,431 (63.1%) were related to adverse
      events and 37,722 (16.4%) were related to generalities about glucocorticoids
      (e.g., what is cortisone? For which disease? How does it work?). Information
      particularly sought by visitors was related to the diet to follow during
      glucocorticoid therapy (page accessed 11,946 times), data about what cortisone is
      (page accessed 11,829 times) and the effects of glucocorticoids on weight (page
      accessed 10,442 times). CONCLUSION: Knowledge of glucocorticoid-treated patients'
      expectations may help physicians to optimize information they give, thereby
      helping to reduce patients' concerns about glucocorticoids and to improve
      adherence to the treatment.

PMID- 23537897
TI  - The birth and early years of INA, the International Neurotoxicology Association.
AB  - The International Neurotoxicology Association (INA) is a scientific society whose
      members have interest and expertise in the discipline of neurotoxicology. The
      idea of forming INA was born in 1984, as a follow-up to a NATO-sponsored meeting
      on Toxicology of the Nervous System. INA held its first meeting in the
      Netherlands in 1987 and has had continuous meetings every other year since then.
      INA is registered as a scientific society in the Netherlands, and is an
      affiliated society of IUTOX. This paper presents a personal account of the events
      that led to the birth of INA, and of the first fifteen years of this association.

PMID- 23537898
TI  - Cellular changes in the enteric nervous system during ageing.
AB  - The intrinsic neurons of the gut, enteric neurons, have an essential role in
      gastrointestinal functions. The enteric nervous system is plastic and continues
      to undergo changes throughout life, as the gut grows and responds to dietary and
      other environmental changes. Detailed analysis of changes in the ENS during
      ageing suggests that enteric neurons are more vulnerable to age-related
      degeneration and cell death than neurons in other parts of the nervous system,
      although there is considerable variation in the extent and time course of age
      related enteric neuronal loss reported in different studies. Specific neuronal
      subpopulations, particularly cholinergic myenteric neurons, may be more
      vulnerable than others to age-associated loss or damage. Enteric degeneration and
      other age-related neuronal changes may contribute to gastrointestinal dysfunction
      that is common in the elderly population. Evidence suggests that caloric
      restriction protects against age-associated loss of enteric neurons, but recent
      advances in the understanding of the effects of the microbiota and the complex
      interactions between enteric ganglion cells, mucosal immune system and intestinal
      epithelium indicate that other factors may well influence ageing of enteric
      neurons. Much remains to be understood about the mechanisms of neuronal loss and
      damage in the gut, although there is evidence that reactive oxygen species,
      neurotrophic factor dysregulation and/or activation of a senescence associated
      phenotype may be involved. To date, there is no evidence for ongoing neurogenesis
      that might replace dying neurons in the ageing gut, although small local sites of
      neurogenesis would be difficult to detect. Finally, despite the considerable
      evidence for enteric neurodegeneration during ageing, and evidence for some
      physiological changes in animal models, the ageing gut appears to maintain its
      function remarkably well in animals that exhibit major neuronal loss, indicating
      that the ENS has considerable functional reserve.

PMID- 23537899
TI  - The loss of Trps1 suppresses ureteric bud branching because of the activation of
      TGF-beta signaling.
AB  - In a previous study, we demonstrated that Trps1-deficient (KO) mice show an
      expanded renal interstitium compared to wild-type (WT) mice because the loss of
      Trps1 affects the mesenchymal-epithelial transition (MET) in the cap mesenchyme
      and ureteric bud (UB) branching. Although we previously elucidated the mechanism
      underlying the impact of Trps1 on the MET, how Trps1 is involved in UB branching
      remains unknown. In the present study, we unveil the molecular mechanisms by
      which the loss of Trps1 suppresses UB branching. When we compared gene expression
      patterns via DNA microarray analysis using cultured ureteric buds isolated from
      E11.5 kidneys of WT and KO embryos, we found aberrant expression of genes
      associated with the transforming growth factor (TGF)-beta/Smad3 signaling pathway
      in the KO UBs. Western blot and immunohistochemistry analyses showed increased
      levels of Rb1cc1, Arkadia1, and phosphorylated Smad3 and decreased levels of
      Smurf2, Smad7, and c-Ski in the KO embryonic kidneys. In addition, TUNEL staining
      and immunohistochemical detection of PCNA revealed that the apoptosis of UB cells
      was upregulated and, conversely, that cell proliferation was suppressed. Finally,
      we demonstrated that the suppression of UB branching in the KO UBs was restored
      via the exogenous addition of the Smad3 inhibitor SIS3, whereas the addition of
      TGF-beta1 accelerated the suppression of UB branching in organ cultures of both
      isolated UBs and whole embryonic kidneys. Considering these results, we conclude
      that UB branching is suppressed through increased activation of the TGF
      beta/Smad3 signaling pathway when Trps1 is lost.

PMID- 23537900
TI  - Central control of peripheral circadian oscillators.
AB  - The suprachiasmatic nucleus of the hypothalamus and at least two other
      unidentified central pacemakers regulate the temporal structure of a circadian
      network that involves almost every organ in the body. Phase control is central to
      the efficient function of this system. Individual circadian oscillators in
      tissues and organs in the periphery bear adaptive phase relationships to the
      external light cycle, the central pacemakers and to each other. The known signals
      that regulate and maintain these phase relationships come from the autonomic
      nervous system, the pineal and adrenal glands, behavioral cycles of feeding and
      activity and the rhythm of body temperature. It is likely that there are many
      unknown signals as well. Disrupting the network can produce severe pathology. 

PMID- 23537901
TI  - Mechanisms of experience dependent control of aggression in crickets.
AB  - Aggression is a highly plastic behaviour, shaped by numerous experiences, and
      potential costs and benefits of competing, to optimize fitness and survival.
      Recent studies on crickets provide insights into how nervous systems achieve
      this. Their fighting behaviour is promoted by physical exertion, winning disputes
      and possession of resources. These effects are each mediated by octopamine, the
      invertebrate analogue of noradrenaline. Submissive behaviour, in less well
      understood. It is induced when the accumulated sum of the opponent's agonistic
      signals surpass some critical level, and probably mediated by nitric oxide,
      serotonin and other neuromodulators. We propose that animals can make the
      decision to fight or flee by modulating the respective behavioural thresholds in
      response to potentially rewarding and aversive attributes of experiences.

PMID- 23537902
TI  - Deep brain stimulation for addiction: why the subthalamic nucleus should be
      favored.
AB  - Surgical treatment for psychiatric disorders has been revitalized for the past
      ten years after deep brain stimulation (DBS) had shown its efficacy for the
      treatment of neurological disorders such as Parkinson's disease. In the field of
      psychiatric disorders, DBS has been first used for obsessive compulsive disorder
      and treatment-resistant depression. Only recently it has been proposed for the
      treatment of addiction. Whatever the disease, the selected target is a constant
      question. In this review, we present theoretical, empirical and technical
      arguments in favor of targeting the subthalamic nucleus as the best candidate
      over other areas for DBS in the treatment of drug addiction. 

PMID- 23537903
TI  - Ascending orexinergic pathways and alcohol-seeking.
AB  - Orexin (hypocretin) containing neurons reside in discrete regions of the lateral
      hypothalamus from where they innervate the entire neuroaxis. Via actions upon
      orexin receptors (OX1 and OX2), the orexin peptides (orexin A and orexin B) are
      thought to play a role in ethanol consumption and seeking. While a role for OX1
      receptors in these behaviours is established, the case for OX2 receptors is less
      clear at present, although recent data certainly support an involvement of OX2
      receptors in ethanol consumption. In terms of circuitry, orexin receptors the
      ventral tegmental area appear to contribute to ethanol consumption. Other loci
      remain to be characterised, and we suggest prefrontal cortical orexin receptors
      deserve attention in this respect. 

PMID- 23537904
TI  - Cement spacers in periprosthetic joint infection.

PMID- 23537905
TI  - Treatment of methicillin-susceptible Staphylococcus aureus osteoarticular and
      prosthetic joint infections: using the oxacillin minimum inhibitory concentration
      to guide appropriate ceftriaxone use.

PMID- 23537906
TI  - Infectious Diseases Society of America guidelines for the diagnosis and
      management of prosthetic joint infection: what is the correct duration of
      antibiotic treatment?

PMID- 23537907
TI  - Recommendations for rifampicin therapy of staphylococcal infection in Infectious
      Diseases Society of America prosthetic Joint Infection Guidelines are not
      supported by available literature.

PMID- 23537908
TI  - Dosing rifampin.

PMID- 23537909
TI  - Reply to Eisen and Denholm, Dauchy et al, Fierer, and Nguyen and Jones.

PMID- 23537910
TI  - Stop routine CD4 monitoring in HIV-infected patients with fully suppressed virus
      and CD4 >=350 cells/ml.

PMID- 23537911
TI  - Chagas disease in Latin American immigrants with dilated cardiomyopathy in New
      York City.
AB  - Chagas disease-associated cardiomyopathy is clinically similar to other causes of
      cardiomyopathy and, therefore, the diagnosis can be easily overlooked. We found a
      13% point prevalence of Chagas disease in a sample of New York City immigrants
      with dilated cardiomyopathy.

PMID- 23537912
TI  - Immunodeficiency-associated lymphoid proliferations (ALPS, HIV, and KSHV/HHV8).
AB  - The World Health Organization recognizes four categories of immunodeficiency
      associated lymphoproliferative disorders (ID-LPDs): (1) lymphoproliferative
      diseases associated with primary immune disorders, (2) lymphomas associated with
      HIV infection, (3) post-transplant LPDs, and (4) other iatrogenic
      immunodeficiency-associated LPDs. Although these lesions are heterogeneous, due
      to their various underlying causes, they share several features, including
      frequent involvement of extranodal sites, diffuse aggressive histology, B-cell
      lineage, associated herpesvirus infection, and rapid clinical progression. The
      accurate diagnosis and treatment of the patients who develop immunodeficiency
      associated LPDs often require careful evaluation of the morphology,
      immunophenotype, genotype, viral status, and clinical history. In this article,
      two of these four categories of ID-LPD are examined: lymphomas associated with
      HIV infections and lymphoproliferative diseases associated with primary immune
      disorders (PIDs), focusing on autoimmune lymphoproliferative syndrome (ALPS), as
      a representative disorder from this latter category.

PMID- 23537913
TI  - Reactive lymphadenopathies that mimic lymphoma: entities of unknown etiology.
AB  - Kikuchi-Fujimoto disease, Kimura disease, Rosai-Dorfman disease and IgG4 related
      lymphadenopathy may present with enlarging masses clinically mimicking lymphoma.
      A combination of clinical and histologic findings is necessary to diagnose these
      important rare entities, which may occasionally have aggressive clinical
      behavior. The recognition of these disorders is important in order to avoid
      misdiagnosis of malignancy, other systemic diseases such as systemic lupus, and
      to institute correct management and therapy, such as steroid treatment for IgG4
      related lymphadenopathy. The underlying etiologies of these diseases are not
      completely clear at present, however, their recognition has become more common as
      diagnostic techniques improve. Their diagnosis and recognition may help to
      elucidate their underlying pathobiology.

PMID- 23537914
TI  - Viral-associated lymphoid proliferations.
AB  - The histological spectrum of viral-associated lymphoid proliferations is quite
      broad, ranging from reactive lymphadenitis to atypical proliferations mimicking
      classical Hodgkin lymphoma or non-Hodgkin lymphoma. Virally associated reactive
      lesions can appear quite alarming on histological examination, because of direct
      (cytopathic) and indirect viral-induced changes eliciting a polymorphic cellular
      host response. In addition, the atypical lymphoid proliferation may show aberrant
      phenotypic features as well as restricted/clonal gene immunoglobulin or T-cell
      receptor rearrangements, further complicating the interpretation. In order to
      achieve an accurate diagnosis, it is important to be aware of the clinical
      history, including family history and ethnic background, clinical presentation,
      symptoms, and extent of the disease. Among the clinical data, particular emphasis
      should be placed on serology and viral load studies, and the use of
      immunosuppressive drugs. The clinical course and outcome vary greatly, from an
      indolent, self-limited to aggressive clinical course, blurring at times the
      distinction between neoplastic and reactive proliferations. It is now recognized
      that immunosenescence also plays a significant role in the development of these
      viral-associated lymphoid proliferations, and new entities have been described in
      recent years. In this review we discuss mostly Epstein-Barr virus-associated
      viral proliferations that may be confused with lymphomas, which the practicing
      pathologist may encounter.

PMID- 23537915
TI  - Is surgical intervention avoidable in cases of emphysematous gastritis? A case
      presentation and literature review.
AB  - INTRODUCTION: Gas located within the gastric wall is a rare finding that is
      associated with a mortality rate of 50%. It confers two main diagnoses: gastric
      emphysema and emphysematous gastritis. Due to its high mortality rate,
      emphysematous gastritis must be differentiated from gastric emphysema early to
      avoid adverse outcomes and plan the management of these patients. PRESENTATION OF
      CASE: We introduce a 55 year-old male who presents with diffuse abdominal pain
      associated with fever, nausea, vomiting, and diarrhea. Patient has positive
      peritoneal signs with fever and leukocytosis. Air in the gastric wall and portal
      venous system was visualized on Computed Tomography (CT). The patient underwent
      emergent laparotomy which showed normal bowel with few adhesions. DISCUSSION:
      Various etiologies can cause gas within the gastric wall but concomitant air in
      the hepatic venous system is highly suspicious for emphysematous gastritis. CT
      imaging is the most sensitive and specific way to differentiate emphysematous
      gastritis versus gastric emphysema. Although rare, there are many cases of
      emphysematous gastritis that undergo prompt surgical exploration. Recently,
      however, medical treatment has become more common and surgical management
      reserved for complications. CONCLUSION: We conclude by stating that this case of
      emphysematous gastritis, due to gastric ulcers, would have no difference in
      outcome if treated medically instead of surgically. Historically, patients with
      emphysematous gastritis warranted surgical intervention. More recently, case
      reports of emphysematous gastritis are favoring conservative management. The
      consensus still remains that there is no standard approach for these patients and
      most patients in extremis are undergoing surgical intervention.

PMID- 23537916
TI  - Ventilator-associated pneumonia prevention by education and two combined bedside
      strategies.
AB  - OBJECTIVE: The objective of the study was to reduce the ventilator-associated
      pneumonia (VAP) incidence rates through a rational prevention program. DESIGN:
      The study was a non-controlled clinical trial with a set of interventions in
      mechanically ventilated patients from April 2006 until June 2008. Pneumonia rates
      were analyzed as time series and their mean risks of development were compared
      before and after the interventions with a non-concurrent cohort using the same
      time frame (January 2004-March 2006). SETTING: The study was conducted in a 14
      bed medical intensive care unit of private general hospital in Rio de Janeiro,
      Brazil. PARTICIPANTS: The study included invasively ventilated patients (n = 224;
      intervention group) compared with 294 controls (historical cohort).
      INTERVENTIONS: An educational module about VAP prevention was introduced at the
      start of the trial (April 2006). A bundle checklist was used daily concomitantly
      with a standardized oral care in all patients afterwards. Main outcome measure
      The main outcome measure was reduction in VAP incidence rates. RESULTS: The
      observed mean rate before the intervention was 18.6 +/- 7.8/1000 ventilator-days
      (95% CI 8.7-14.9), decreasing to 11.8 +/- 7.8/1000 ventilator-days (95% CI 15.5
      21.7) (P = 0.002) after the interventions. Under the adoption of non-informative
      prior distributions for the parameters of the proposed statistical model, there
      was a 70% posterior probability in favor of the hypothesis of risk reduction
      associated with the interventions, regardless their seasonality or secular
      trends. There was a 38% relative risk reduction. CONCLUSIONS: A reduction in VAP
      rates and on their risk after a set of preventive tools was observed. However,
      some other co-interventions not related to the primary interventions may have
      contributed to these results.

PMID- 23537917
TI  - Patient safety incident-reporting items in Korean hospitals.
AB  - OBJECTIVE: To examine incident-reporting items in tertiary hospitals using the
      framework of the World Health Organization's International Classification for
      Patient Safety (ICPS). DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS:
      Forty acute-care tertiary hospitals in Korea (response rate = 90.9%). METHODS:
      Data were collected using a semistructured questionnaire during on-site
      interviews or via e-mail. Items were extracted from incident-reporting forms that
      required a reporter's input, and were analyzed using the ICPS framework. After
      removing redundant items, unique reporting items were mapped onto ICPS elements.
      The data are summarized using descriptive statistics. RESULTS: On average,
      hospitals used 2.4 incident-reporting forms (range = 1-9) and 136.7 reporting
      items (range = 31-310). All of the hospitals had incident-reporting items that
      described 'incident type' and 'incident characteristics'; however, only 7
      hospitals (17.5%) had reporting items on incident 'detection', and 18 hospitals
      (45.0%) collected information on the 'organizational outcomes'. Of the 1145
      unique reporting items, 297 (25.9%) were completely mapped onto ICPS elements at
      different levels of granularity, and 12.7% (n = 145) were mapped onto ICPS
      elements that had more granular subcategories. CONCLUSIONS: The ICPS framework is
      a useful reference model for the classification of incident-reporting items.
      However, further refinements to both the ICPS framework and incident-reporting
      items are needed in order to better represent data on patient safety.
      Furthermore, the use of a common reporting form at the national level is
      recommended for reducing variations in reporting items and facilitating the
      efficient collection and analysis of patient safety data.

PMID- 23537918
TI  - Longitudinal wave propagation in multi cylindrical viscoelastic matching layers
      of airborne ultrasonic transducer: new method to consider the matching layer's
      diameter (frequency <100 kHz).
AB  - Wave propagation in viscoelastic disk layers is encountered in many applications
      including studies of airborne ultrasonic transducers. For viscoelastic materials,
      both material and geometric dispersion are possible when the diameter of the
      matching layer is of the same order as the wavelength. Lateral motions of the
      matching layer(s) that result from the Poisson effect are accounted by using a
      new concept called the "effective-density". A new wave equation is derived for
      both metallic and non-metallic (polymeric) materials, usually employed for the
      matching layers of airborne ultrasonic transducer. The material properties are
      modeled by using the Kelvin model for metals and Linear Solid Standard model for
      non-metallic (polymeric) matching layers. The utilized model of the material of
      the matching layers has influence on amount and trend of variation in speed
      ratio. In this regard, 60% reduction in speed ratio is observed for Kelvin model
      for aluminum with diameter of 80 mm at 100 kHz while for a similar diameter but
      Standard Linear Model, the speed ratio increase to twice value at 15 kHz, and
      then reduced until 70% at 67 kHz for Polypropylene. The new wave theory
      simplifies to the one-dimensional solution for waves in metallic or polymeric
      matching layers if the Poisson ratio is set to zero. The predictions simplify to
      Love's equation for stress waves in elastic disks when loss term is removed from
      equations for both models. Afterwards, the new wave theory is employed to
      determine the airborne ultrasonic matching layers to maximize the energy
      transmission to the air. The optimal matching layers are determined by using
      genetic algorithm theory for 1, 2 and 3 airborne matching layers. It has been
      shown that 1-D equation is useless at frequencies less than 100 kHz and the
      effect of diameter of the matching layers must be considered to determine the
      acoustic impedances (matching layers) to design airborne ultrasonic transducers.

PMID- 23537919
TI  - Reducing crosstalk in array structures by controlling the excitation voltage of
      individual elements: a feasibility study.
AB  - This paper describes a procedure to minimize crosstalk between the individual
      elements of a piezoelectric transducer array. A two-dimensional finite elements
      model was developed and the excitation voltages predicted by the model were
      applied to the array prototypes made of PZT 27 ceramic. Symmetric and asymmetric
      linear phased arrays operating at approximately 450 kHz were tested in the
      feasibility study. The studies were carried out at low frequency to facilitate
      the fabrication of the transducer arrays and to check the feasibility in this
      case. The novelty of our approach is to offer active cancellation of crosstalk in
      transducer arrays generating continuous waves, even in the presence of
      fabrication defects. The experimental results showed the validity of the approach
      and demonstrated that crosstalk can be reduced by about 6-10 dB. In ultrasonic
      imaging systems, this method could be introduced by using a multichannel
      generator providing electrical signals containing both phased signals required to
      focalize and deflect the acoustic beam associated with the correction signals.

PMID- 23537920
TI  - Association of treatment for bacterial meningitis with the development of
      sequelae.
AB  - BACKGROUND: Bacterial meningitis continues to be a serious, often disabling
      infectious disease. The aim of this study was to assess the possibility that
      treatment influences the development of sequelae in childhood bacterial
      meningitis. METHODS: Two thousand four hundred and seventy-seven patients aged 1
      month to 14 years with acute bacterial meningitis over a 32-year period were
      enrolled in the study. Data were collected prospectively from the Meningitis
      Registry of a tertiary university teaching hospital in Athens, Greece. Treatment
      was evaluated through univariate and multivariate analysis with regard to
      sequelae: seizure disorder, severe hearing loss, ventriculitis, and
      hydrocephalus. RESULTS: According to the multinomial logistic regression
      analysis, there was evidence that penicillin, an all-time classic antibiotic, had
      a protective effect on the occurrence of ventriculitis (odds ratio (OR) 0.17, 95%
      confidence interval (CI) 0.05-0.60), while patients treated with chloramphenicol
      had an elevated risk of ventriculitis (OR 17.77 95% CI 4.36-72.41) and seizure
      disorder (OR 4.72, 95% CI 1.12-19.96). Cephalosporins were related to an
      increased risk of hydrocephalus (OR 5.24, 95% CI 1.05-26.29) and ventriculitis
      (OR 5.72, 95% CI 1.27-25.76). The use of trimethoprim/sulfamethoxazole increased
      the probability of seizure disorder (OR 3.26, 95% CI 1.08-9.84) and ventriculitis
      (OR 8.60, 95% CI 2.97-24.91). Hydrocortisone was associated with a rise in
      hydrocephalus (OR 5.44, 95% CI 1.23-23.45), while a protective effect of
      dexamethasone (OR 0.82, 95% CI 0.18-3.79) was not statistically significant.
      CONCLUSIONS: Current study findings suggest that the type of antimicrobial
      treatment for childhood bacterial meningitis may influence in either a positive
      or a negative way the development of neurological sequelae.

PMID- 23537921
TI  - Respiratory emergencies in children.

PMID- 23537922
TI  - A concurrent-choice analysis of amount-dependent temporal discounting.
AB  - Amount-dependent temporal discounting refers to the differential rates at which
      the values of large and small rewards are discounted over time. A lower rate of
      discounting of larger rewards is known as the magnitude effect. The present study
      aimed to establish a magnitude effect in humans using a concurrent-choice
      procedure. Participants indicated their strength of preference between
      hypothetical outcomes that differed in monetary value, and in the delay at which
      they were available. Most studies of temporal discounting measure preference
      using indifference points estimated from a titration procedure. The present study
      measured preference using a concurrent choice procedure. The main analysis
      demonstrated temporal discounting and a magnitude effect. Further analysis showed
      that the result was consistent with the matching law. 

PMID- 23537923
TI  - Meta-analysis of the effects of MI training on clinicians' behavior.
AB  - MI-based interventions are widely used with a number of different clinical
      populations and their efficacy has been well established. However, the
      clinicians' training has not traditionally been the focus of empirical
      investigations. We conducted a meta-analytic review of clinicians' MI-training
      and MI-skills findings. Fifteen studies were included, involving 715 clinicians.
      Pre-post training effect sizes were calculated (13 studies) as well as group
      contrast effect sizes (7 studies). Pre-post training comparisons showed medium to
      large ES of MI training, which are maintained over a short period of time. When
      compared to a control group, our results also suggested higher MI proficiency in
      the professionals trained in MI than in nontrained ones (medium ES). However,
      this estimate of ES may be affected by a publication bias and therefore, should
      be considered with caution. Methodological limitations and potential sources of
      heterogeneity of the studies included in this meta-analysis are discussed. 

PMID- 23537924
TI  - Changes in tobacco use patterns among adolescents in substance abuse treatment.
AB  - The purpose of this study was to determine tobacco use and dependence patterns
      over the course of 12 months among an adolescent population entering substance
      abuse treatment. The sample consisted of intake and 3-, 6-, and 12-month post
      intake tobacco use data from 1062 adolescents within 34 substance abuse treatment
      facilities across the United States. Data were pooled across sites and analyzed
      utilizing descriptive statistics; repeated measures analyses; multiple regression
      models; three-level hierarchical linear models; and hierarchical generalized
      linear modeling. The majority of the sample reported at least weekly tobacco use
      at intake. Over time, participants increased their total tobacco consumption and
      days of use while reporting less desire for help with cessation. Race/ethnicity
      was a factor in differing tobacco use patterns. Tobacco dependence rates remained
      stable from intake to 3 months post-intake, decreased at 6 months post-intake,
      and rose to its highest levels at 12 months post-intake. Participants attended
      one smoking cessation class on average in each 90 day time period. Results
      suggest that adolescents entering substance use treatment may benefit from
      integrated tobacco cessation interventions that are intensive and occur early in
      treatment.

PMID- 23537926
TI  - Antibiotic treatment for acute otitis media.
AB  - 93% of patients at a GP practice in Surrey were given antibiotics for acute
      otitis media over a year. Only 52% of these antibiotics were given according to
      the NICE guideline criteria, offering massive scope for a more rationalised
      approach to antibiotic prescribing. Given the huge importance of controlling
      antibiotic resistance and the large incidence of acute otitis media, any reforms
      could potentially massively reduce unnecessary antibiotic prescriptions in the
      community.

PMID- 23537925
TI  - Complement activation in pediatric patients with recurrent acute otitis media.
AB  - OBJECTIVE: Otitis media (OM) is one of the most common childhood diseases. The
      relative contribution of complement activation in protection and pathogenesis
      during OM remains largely unknown. The purpose of this study was to investigate
      the beneficial and pathogenic contributions of complement activation in the
      middle ear of pediatric patients with recurrent acute otitis media (rAOM), and
      therefore to provide a rational approach to prevent sequelae of OM such as
      hearing loss. METHODS: Twenty children undergoing pressure equalization tube
      placement with or without adenoidectomy for rAOM were enrolled in the study.
      Bacterial cultures, enzyme-linked immunosorbent assay (ELISA) for complement
      components and cytokines and western blot for complement activation were
      performed on middle ear effusion (MEE) and serum samples. The levels of
      complement C3a, C5a and sC5-b9 in MEEs and serum samples were compared. The
      levels of these factors were also examined in regards to length of episode.
      Pearson's correlation coefficients were calculated on variables between C5a and
      IL-6 or IL-8. Complement gene expression in human middle ear epithelial (HMEE)
      cells induced by otopathogens was evaluated. Data were analyzed with Student's t
      test or the Mann-Whitney rank sum test. In all cases, a P value of <0.05 was set
      as the measure of significance. RESULTS: Our data demonstrated that the
      complement classical/lectin, alternative and terminal pathways were activated in
      the middle ear of children with rAOM. Increased complement components of C3a, C5a
      and sC5-b9 in MEEs were detected in patients with the episode lasting more than
      six weeks. There was a strong correlation between C5a and IL-6 or IL-8 in the
      MEEs. Additionally, otopathogens induced enhanced gene expression of factor B and
      C3 in HMEE cells, which is beneficial for host defense against invading
      pathogens. CONCLUSION: Our studies provided important new insights on how
      complement activation contributes to inflammatory process during rAOM. Knowledge
      of the activity of the complement pathway in patients with rAOM may stimulate the
      development of new strategies to prevent middle ear inflammatory tissue
      destruction by directing treatment to specific pathways within the complement
      cascade.

PMID- 23537927
TI  - Pediatric tracheotomy: are the indications changing?
AB  - OBJECTIVE: The most common indications for tracheotomy in pediatric patients
      include upper airway obstruction, prolonged ventilator dependence, and hypotonia
      secondary to neurologic impairment. In this study we review the indications for
      tracheotomy within our patient population over the last 11 years. METHODS: We
      conducted a retrospective chart review of consecutive patients undergoing
      tracheotomy at a tertiary care pediatric hospital from January 2000 to April
      2011. We evaluated patient age, sex, pre-operative and post-operative diagnosis,
      and direct laryngoscopic and bronchoscopic findings. Patients were divided into
      six groups based on their indication for tracheotomy. In order to assess changing
      indications for tracheotomy over time, we compared an early (2000-2005) and a
      late (2006-2011) patient group. RESULTS: We had complete data available on
      158/165 patients (95.8%) who underwent tracheotomy from 2000 to 2011. There was
      no significant difference in mean age between the early and late groups (4.73 +/-
      6.0 years vs. 3.6 +/- 5.5 years, p=0.26). There was a change in the most common
      indication for tracheotomy between the early and late groups, with upper airway
      obstruction becoming more common in the late group and significantly fewer
      patients undergoing tracheotomy for prolonged ventilation in the late group
      (33/76 (43%) vs. 23/82 (28%), p=0.05). More patients underwent bronchoscopy at
      the time of tracheotomy in the late group (52/82 (63%) vs. 28/76 (37%), p=<0.01).
      CONCLUSION: A review of our pediatric tracheotomy experience demonstrated a
      change in the most common indication for tracheotomy between 2000 and 2011. In
      our patient population, there was a significant decline in the number of
      tracheotomies performed for prolonged intubation and an increasing number of
      patients who required tracheotomy for upper airway obstruction.

PMID- 23537928
TI  - The effect of tongue-tie division on breastfeeding and speech articulation: a
      systematic review.
AB  - OBJECTIVE: To systematically review the outcomes of tongue-tie division
      procedures in patients with ankyloglossia with the goal of (1) deriving
      clinically oriented insights into the effect of tongue-tie division procedures
      and (2) identifying needs in knowledge to stimulate further research. DATA
      SOURCES: Medline, EMBASE, and Cochrane databases were searched without any
      limitations, for studies published between 1966 and June 2012. REVIEW METHODS:
      Studies were included (level 4 evidence or above) if subjects of any age had
      ankyloglossia and underwent tongue-tie release. Outcome measures of interest were
      any subjective or objective measures of breastfeeding and speech outcomes, or
      reports of adverse events. RESULTS: In all, 378 abstracts were generated from the
      literature searches; 20 studies met the criteria for data extraction and
      analysis. Of those, 15 studies were observational and 5 were randomized
      controlled trials. Tongue-tie division provided objective improvements in the
      following: LATCH scores (3 studies); SF-MPQ index (2 studies); IBFAT (1 study);
      milk production and feeding characteristics (3 studies); and infant weight gain
      (1 study). Subjective improvements were also noted in maternal perception of
      breastfeeding (14 studies) and maternal pain scores (4 studies). No definitive
      improvements in speech function were reported. The only significant adverse
      events were recurrent tongue-ties that required repeat procedures. CONCLUSION:
      Ankyloglossia is a well-tolerated procedure that provides objective and
      subjective benefits in breastfeeding; however, there was a limited number of
      studies available with quality evidence. There are no significant data to suggest
      a causative association between ankyloglossia and speech articulation problems.
      Aspects of ankyloglossia that would benefit from further research are described,
      and recommendations for tongue-tie release candidacy criteria are provided.

PMID- 23537929
TI  - Relation of vascular stiffness with epicardial and pericardial adipose tissues,
      and coronary atherosclerosis.
AB  - OBJECTIVES: Increased measured vascular stiffness is an early marker of
      atherosclerosis and is associated with cardiovascular risk factors. Coronary
      artery calcium (CAC) and adipose tissues are accurate markers of overall burden
      of coronary atherosclerosis and metabolic status, respectively. We evaluated the
      relation of vascular stiffness with epicardial (EAT) and pericardial (PAT)
      adipose tissues, as well as the presence and severity of CAC. METHODS: One
      hundred and eleven consecutive subjects, mean age 59 +/- 11 years, 78% male,
      underwent 64-multidetector row cardiac computed tomography (MDCT) and their
      carotid-radial pulse wave velocity (PWV) was measured using SphygmoCor tonometry.
      EAT and total thoracic adipose tissue (TAT) volumes were measured using MDCT. PAT
      was calculated as TAT-EAT. The highest tertile of EAT (>=111 ml) and PAT (>=103
      ml) were defined as significant adipose tissue depots. RESULTS: PWV was
      moderately associated with EAT (r = 0.46, p < 0.001), and PAT (r = 0.41, p <
      0.001). PWV increased proportionally with the severity of CAC from 0 to 400+. The
      relative risk of highest vs. lowest tertile of PWV was 3.03 (95% CI 1.22-7.51, p
      = 0.01) for significant EAT, 2.34 (95% CI 1.10-4.90, p = 0.02) for significant
      PAT and 2.46 (95% CI 1.13-3.14, p = 0.01) for significant CAC (CAC 100+) after
      adjustment for conventional cardiovascular risk factors. This relative risk was
      increased after combination of CAC 100+ with each significant adipose tissue.
      CONCLUSIONS: Increased vascular stiffness is associated with increase in EAT, PAT
      and coronary atherosclerosis. EAT was associated with higher relative risk of
      PWV, compared with CAC, suggesting a role of adipose tissue in vascular
      stiffness.

PMID- 23537930
TI  - Molecular Immunology. Preface.

PMID- 23537931
TI  - Ultrasound-guided cerebrospinal fluid collection from rats.

PMID- 23537932
TI  - Comparative performance evaluation of data-driven causality measures applied to
      brain networks.
AB  - In this article, several well-known data-driven causality methods are revisited
      and comparatively evaluated. These are the Granger-Geweke Causality (GGC), the
      Partial Directed Coherence (PDC), the Directed Transfer Function (DTF) and the
      Direct Directed Transfer Function (dDTF). The robustness of the four causality
      measures against two degradation factors is quantitatively evaluated. These are:
      the presence of realistic biological/electronic noise at various SNR levels, as
      recorded on a MagnetoEncephalography (MEG) machine, and the presence of a weak
      node in the brain network where the causality analysis is applied. The causality
      measures are evaluated in terms of the relative estimation error and the
      compromise between true and fictitious causal density in the brain network. Both
      parametric and non-parametric causality analysis is performed. It is illustrated
      that the non-parametric method is a promising alternative to the more commonly
      applied MVAR-model based causality analysis. It is also demonstrated that, in the
      presence of both tested degradation factors, the DTF method is the most robust in
      terms of low estimation error, while the PDC in terms of low fictitious causal
      density. The dDTF provides lower fictitious causal density and higher spectral
      selectivity as compared to DTF, at high enough SNR. The GGC exhibits the worst
      compromise of performance. An application of the causality measures to a set of
      MEG resting-state experimental data is accordingly presented. It is demonstrated
      that significant contrast between the Eyes-Closed and Eyes-Open rest condition in
      the alpha frequency band allows to detect significant causality between the
      occipital cortex and the thalamus.

PMID- 23537933
TI  - Pre-analytical factors influencing the stability of cerebrospinal fluid proteins.
AB  - Cerebrospinal fluid (CSF) is a potential source for new biomarkers due to its
      proximity to the brain. This study aimed to clarify the stability of the CSF
      proteome when undergoing pre-analytical factors. We investigated the effects of
      repeated freeze/thaw cycles, protease inhibitors and delayed storage for 4h, 24h
      or 14 days at -20 degrees C, 4 degrees C and room temperature (RT) after
      centrifugation compared with our standard practice of two hours at RT before
      placing the samples in an -80 degrees C environment. The results were obtained
      using immunoassays for amyloid-beta 1-42 (Abeta42), tau, phosphorylated tau (P
      tau) and cystatin C and using surface-enhanced laser desorption/ionisation time
      of-flight (SELDI-TOF) mass spectrometry for proteomic profiling. Tau and P-tau
      were susceptible to repeated freeze/thaw cycles while SELDI-TOF analysis produced
      eight significant peaks and additional artefact peaks from samples with added
      protease inhibitors. Delayed storage for different durations and in different
      temperatures produced six significant SELDI-TOF peaks. Abeta42 and tau were
      susceptible to increased temperatures and the duration before storage, whereas P
      tau and cystatin C were not. Transthyretin and several of its isoforms were found
      using SELDI-TOF and were susceptible to freeze/thaw cycles and to increased
      temperature and length of time prior to storage. We recommend that CSF should be
      collected and centrifuged immediately after sampling and prior to storage at -80
      degrees C without the addition of protease inhibitors. Freeze/thawing should be
      avoided because of the instability of tau, P-tau and transthyretin. Standardised
      CSF sampling, handling and storage for biomarker research are essential for
      accurately comparing the results obtained by different studies and institutions.

PMID- 23537934
TI  - Development of an enzyme-linked immunosorbent assay (ELISA) to measure the level
      of tyrosine hydroxylase protein in brain tissue from Parkinson's disease models.
AB  - Tyrosine hydroxylase (TH) catalyses the rate-limiting step in the biosynthesis of
      catecholamines. TH expression is regulated in a tissue-specific manner during
      neuronal development and differentiation. Because of its key regulatory role in
      central and peripheral catecholamine synthesis, TH is associated with the
      pathogenesis of several neurological and psychiatric diseases, including
      Parkinson's disease, dystonia, schizophrenia, affective disorders, and
      cardiovascular diseases. Therefore, developing a quantitative method to monitor
      the changes in TH expression in disease models could facilitate the
      identification and characterisation of neuromodulatory and neuroprotective
      therapeutic agents. The present report describes the generation and
      characterisation of a new set of monoclonal TH antibodies and the development of
      a novel sandwich ELISA for the quantitative detection of the TH protein in rodent
      brain tissue. This ELISA exhibits excellent reproducibility and good linearity in
      the analysis of complex brain tissue lysates. The cross-validation of the TH
      ELISA using semi-quantitative TH Western blot methods and HPLC measurement of
      dopamine levels suggests that the new TH ELISA is sufficiently sensitive to
      detect small-to-moderate region-specific differences, developmental changes, and
      Parkinson's disease-related changes in TH expression in rodent brains. This new
      TH ELISA also offers greater flexibility than conventional HPLC-based dopamine
      assays because the optimal tissue lysis buffer used for the detection of TH in
      brain tissue is also compatible with the analysis of other proteins associated
      with Parkinson's disease, such as alpha-synuclein, suggesting that this TH ELISA
      could be used in a multiplexed format.

PMID- 23537935
TI  - Paraffin sections of 70-100 MUm: a novel technique and its benefits for studying
      the nervous system.
AB  - This technical communication provides a protocol for processing paraffin-embedded
      tissue blocks from the nervous system sectioned at 70-100 MUm. Staining is
      performed on free-floating sections. Unlike 4-15 MUm thick paraffin sections,
      this technique permits (1) the accurate recognition of specific cell types and
      cytoarchitectonic units (subcortical nuclei and cortical layers) and, owing to
      the superimposition of large numbers of biological structures, (2) the accurate
      assessment of pathological changes, e.g., those associated with
      synucleinopathies, tauopathies, and TDP-43 proteinopathies.

PMID- 23537937
TI  - Do EEG paradigms work in fMRI? Varying task demands in the visual oddball
      paradigm: Implications for task design and results interpretation.
AB  - We investigate the effects of variations in response requirements on BOLD
      activation in a visual oddball task and consider implications for fMRI task
      designs. Sixteen healthy subjects completed 3 runs of a visual oddball task:
      passive, count and respond. Besides expected activation patterns during passive
      viewing, we identified joint activations, but more importantly crucial
      differences between the count and respond versions of the task. Middle frontal
      gyrus activation was seen in the respond but not the count condition suggesting
      that this region is associated with action execution rather than the decision
      making aspect of the task. In addition, activation observed in the central
      opercular cortex and parietal operculum in the respond (but not count) condition
      is likely to reflect integration of the sensory, decision and response processes.
      We also observed activation in the supplementary motor area (SMA) during count as
      well as respond. Since the count condition requires no motor planning or response
      our data provide evidence for an SMA involvement in decision-making. Our study
      clearly shows that the count and respond versions of the visual oddball task
      result in different patterns of BOLD activation that could both be attributed to
      'target detection' if information on the respective other condition was not
      available. We also show that considering the elements of a complex task is
      crucial when transferring it from one imaging modality to another and that a
      motor response is not always necessary in fMRI studies when the task has been set
      up appropriately.

PMID- 23537936
TI  - 5-HT1A sex based differences in Bmax, in vivo KD, and BPND in the nonhuman
      primate.
AB  - Serotonin (5-HT) dysfunction has been implicated in neuropsychiatric illnesses
      and may play a pivotal role in the differential prevalence of depression between
      the sexes. Previous PET studies have revealed sex-based differences in 5-HT1A
      binding potential (BPND). The binding potential is a function of the radioligand
      receptor affinity (1/KDapp), and receptor density (Bmax). In this work, we use a
      multiple-injection (MI) PET protocol and the 5-HT1A receptor antagonist,
      [(18)F]mefway, to compare sex-based differences of in vivo affinity, Bmax, and
      BPND in rhesus monkeys. METHODS: PET [(18)F]mefway studies were performed on 17
      (6m, 11f) rhesus monkeys using a 3-injection protocol that included partial
      saturation injections of mefway. Compartmental modeling was performed using a
      model to account for non-tracer doses of mefway for the estimation of KDapp and
      Bmax. BPND estimates were also acquired from the first injection (high specific
      activity [(18)F]mefway, 90-minute duration) for comparison using the cerebellum
      (CB) as a reference region. Regions of interest were selected in 5-HT1A binding
      regions of the hippocampus (Hp), dorsal anterior cingulate cortex (dACC),
      amygdala (Am), and raphe nuclei (RN). RESULTS: Female subjects displayed
      significantly (*p<0.05) lower KDapp in the Hp (-32%), Am (-38%), and RN (-37%).
      Only the Hp displayed significant differences in Bmax with females having a Bmax
      of -29% compared to males. Male subjects demonstrated significantly lower BPND
      measurements in the Am (14%) and RN (29%). CONCLUSION: These results suggest that
      the higher BPND values found in females are the result of lower [(18)F]mefway
      KDapp. Although a more experimentally complex measurement, separate assay of
      KDapp and Bmax provides a more sensitive measure than BPND to identify the
      underlying differences between females and males in 5-HT1A function.

PMID- 23537938
TI  - A multi-atlas based method for automated anatomical Macaca fascicularis brain MRI
      segmentation and PET kinetic extraction.
AB  - MRI templates and digital atlases are needed for automated and reproducible
      quantitative analysis of non-human primate PET studies. Segmenting brain images
      via multiple atlases outperforms single-atlas labelling in humans. We present a
      set of atlases manually delineated on brain MRI scans of the monkey Macaca
      fascicularis. We use this multi-atlas dataset to evaluate two automated methods
      in terms of accuracy, robustness and reliability in segmenting brain structures
      on MRI and extracting regional PET measures. METHODS: Twelve individual Macaca
      fascicularis high-resolution 3DT1 MR images were acquired. Four individual
      atlases were created by manually drawing 42 anatomical structures, including
      cortical and sub-cortical structures, white matter regions, and ventricles. To
      create the MRI template, we first chose one MRI to define a reference space, and
      then performed a two-step iterative procedure: affine registration of individual
      MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs.
      Automated segmentation in native space was obtained in two ways: 1) Maximum
      probability atlases were created by decision fusion of two to four individual
      atlases in the reference space, and transformation back into the individual
      native space (MAXPROB)(.) 2) One to four individual atlases were registered
      directly to the individual native space, and combined by decision fusion
      (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the
      volume difference. The robustness and reproducibility of PET regional
      measurements obtained via automated segmentation was evaluated on four co
      registered MRI/PET datasets, which included test-retest data. RESULTS: Dice
      indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with
      all four individual atlases. There was no significant mean volume bias. The
      standard deviation of the bias decreased significantly when increasing the number
      of individual atlases. MAXPROB performed better when increasing the number of
      atlases used. When all four atlases were used for the MAXPROB creation, the
      accuracy of morphometric segmentation approached that of the PROPAG method. PET
      measures extracted either via automatic methods or via the manually defined
      regions were strongly correlated, with no significant regional differences
      between methods. Intra-class correlation coefficients for test-retest data were
      over 0.87. CONCLUSIONS: Compared to single atlas extractions, multi-atlas methods
      improve the accuracy of region definition. They also perform comparably to
      manually defined regions for PET quantification. Multiple atlases of Macaca
      fascicularis brains are now available and allow reproducible and simplified
      analyses.

PMID- 23537939
TI  - Nursing educators' perspectives of students with disabilities: a grounded theory
      study.
AB  - The purpose of this grounded theory study was to increase understanding of
      nursing educators' perspectives of students with disabilities. Seventeen
      educators from four nursing education programs in western Canada participated.
      The theory emerging from this data was "producing competent graduates". The
      central category was supporting students to become competent graduates. This
      paper focuses on the nursing educators' perspectives of students with
      disabilities, which influenced their efforts to support students with
      disabilities on that path. 

PMID- 23537940
TI  - Are health science students' beliefs about infant nutrition evidence-based?
AB  - BACKGROUND: Globally, breastfeeding is a fundamental health promotion strategy,
      improving the health of mothers and infants, well beyond childhood. Healthcare
      professionals have the responsibility of providing breastfeeding education to
      families. Worldwide, most healthcare professionals do not receive sufficient
      evidence-based education to adequately support breastfeeding families.
      OBJECTIVES: (1) What experiences have university health science students had with
      breastfeeding? (2) What are university health science students' beliefs and
      attitudes toward breast and formula feeding of infants? (3) What are the
      perceptions of university health science students about how other important
      people in their lives regard breastfeeding? (4) What are the relationships
      between students' personal experiences with breastfeeding and their beliefs and
      attitudes about infant feeding choices? DESIGN: A descriptive cross-sectional
      survey conceptualized using the Theory of Planned Behavior. SETTING: The health
      science college within a major metropolitan research university in the United
      States. PARTICIPANTS: Health science undergraduate and graduate students (N=514),
      who were over the age of 18 and who were enrolled during the spring of 2011.
      METHODS: Validated survey instruments were used to collect the data on the Theory
      of Planned Behavior variables. The request for participants was done by emailing
      all health science students. If students chose to participate, they filled out an
      anonymous on-line survey. RESULTS: Most participants were not parents; however,
      the majority of the 95 (21.05%) students who were parents reported their child
      was breastfed. Significantly more positive attitudes and beliefs were found in
      graduate students (n=101; 20.10%) when compared to undergraduates (n=403; 89.9%).
      CONCLUSIONS: Health science students' beliefs and attitudes toward infant
      nutrition often were not evidence-based. However, all students were remarkably
      consistent in their responses concerning formula feeding. Incorporating adequate
      education about human lactation is an unmet responsibility of university health
      science programs.

PMID- 23537941
TI  - The presentation of depression in the British Army.
AB  - BACKGROUND: The British Army is predominately composed of young men, often from
      disadvantaged backgrounds, in which Depression is a common mental health
      disorder. OBJECTIVES: To construct a predictive model detailing the presentation
      of depression in the army that could be utilised as an educational and clinical
      guideline for Army clinical personnel. METHOD AND PARTICIPANTS: Utilising a
      Constructivist Grounded Theory, phase 1 consisted of 19 interviews with
      experienced Army mental health clinicians. Phase 2 was a validation exercise
      conducted with 3 general practitioners. RESULTS: Depression in the Army
      correlates poorly with civilian definitions, and has a unique interpretation.
      CONCLUSION: Young soldiers presented with symptoms not in the International
      Classification of Disorders and older soldiers who feared being medically
      downgraded, sought help outside the Army Medical Services. Women found it easier
      to seek support, but many were inappropriately labelled as depressed.
      Implications include a need to address the poor understanding of military
      stressors; their relationships to depressive symptoms and raise higher awareness
      of gender imbalances with regard to access and treatment. The results have
      international implications for other Armed forces, and those employed in Young
      Men's Mental Health. The results are presented as a simple predictive model and
      aide memoire that can be utilised as an educational and clinical guideline. There
      is scope to adapt this model to international civilian healthcare practice.

PMID- 23537942
TI  - Anticancer activity of novel hybrid molecules containing 5-benzylidene
      thiazolidine-2,4-dione.
AB  - Hybridization of two different bioactive molecules with different mechanism of
      action is one of the methods that are being adopted to treat cancer. Molecules
      bearing a thiazolidine-2,4-dione scaffold have been recognized as antineoplastic
      agents with a broad spectrum of activity against many cancer cell lines. In this
      manuscript we have described the synthesis and biological evaluation of two
      series of N-3-substituted-5-arylidene thiazolidine-2,4-diones, bearing the alpha
      bromoacryloylamido moiety at the para- or meta-position on the phenyl of the
      arylidene portion. We have observed that selected compounds 5a, 5c and 5g
      suppress proliferation of human myeloid leukaemia HL-60 and U937 cells by
      triggering morphological changes and internucleosomal DNA fragmentation, which
      are well-known features of apoptosis. Finally, our results indicated that the
      investigated compounds induced apoptotic cell death through a mechanism that
      involved activation of multiple caspases and was also associated with the release
      of cytochrome c from the mitochondria.

PMID- 23537943
TI  - Novel pyrimidoazepine analogs as serotonin 5-HT(2A) and 5-HT(2C) receptor ligands
      for the treatment of obesity.
AB  - Obesity is one of the most serious public health problems worldwide in the 21st
      century. Current therapeutic treatment for obesity is mostly focused on
      preventive measures involving dietary control and physical exercises in
      combination with anti-obesity medications. However, most of these anti-obesity
      medications have little or no effect on weight loss, and some cases have
      demonstrated fatal side effects. Due to the urgent need for highly potent and
      selective anti-obesity agents, the serotonin receptors (5-HTR) have been the
      focus of much interest as a novel therapeutic target. In this report, we have
      developed pyrimidoazepine analogs targeting the 5-HT2A and 5-HT2C receptors and
      evaluated their biological activity in vitro and in vivo as novel anti-obesity
      agents. We were able to identify 6p as the most potent 5-HT2A and 5-HT2C ligand
      in vitro (IC50 = 3 nM and 2.3 nM, respectively), and this compound also
      demonstrated the greatest potency in vivo. In an acute obesity model, mice
      treated with 6p showed significant decrease in body weight gain and food intake
      over approximately 77-94% compared to a control group. In a chronic obesity
      model, mice treated with 6p also showed a marked decrease in food intake and body
      weight gain.

PMID- 23537944
TI  - Isolation and characterization of new genetic types of Toxoplasma gondii and
      prevalence of Trichinella murrelli from black bear (Ursus americanus).
AB  - Black bears (Ursus americanus) are hosts for two important zoonotic parasites,
      Toxoplasma gondii and Trichinella spp. and bears are hunted for human consumption
      in the USA. Little is known of the genetic diversity of T. gondii circulating in
      wildlife. In the present study, antibodies to T. gondii were found in juice from
      tongues of 17 (25.7%) of 66 wild black bear from Maryland during the hunting
      season of 2010 and 2011. Antibodies to T. gondii were assessed by the modified
      agglutination test. Tongues of 17 seropositive bears were bioassayed in mice and
      viable T. gondii was isolated from three samples. These three T. gondii isolates
      (TgBbMd1-3) were further propagated in cell culture and DNA isolated from culture
      derived tachyzoites was characterized using 11 PCR-RFLP markers (SAG1, 5'- and 3'
      SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico). Results
      revealed three genotypes. TgBbMd1 is a Type 12 strain (ToxoDB PCR-RFLP genotype
      #4) and TgBbMd2 is ToxoDB PCR-RFLP genotype #216, and TgBbMd3 is a Type II clonal
      strain (ToxoDB PCR-RFLP genotype #1). The isolate TgBbMd2 was highly virulent for
      outbred Swiss Webster mice; all infected mice died of acute toxoplasmosis.
      Results indicate that mouse virulent strains of T. gondii are circulating in
      wildlife in the USA. These 66 tongues in addition to tongues collected during
      hunts in previous years were further investigated for the presence of muscle
      larvae of Trichinella spp. Tongues from 40 bears in 2005, 41 in 2006, 51 in 2007,
      56 in 2008, 68 in 2009, 67 in 2010, and 66 in 2011 were subjected to digestion
      with pepsin/HCl and microscopic examination. Two bears were infected with
      Trichinella spp.; one in 2008 and one in 2009. Genotyping of collected muscle
      larvae revealed that the infecting species in both cases was Trichinella
      murrelli.

PMID- 23537945
TI  - Antibody kinetics in goats and conceptuses naturally infected with Neospora
      caninum.
AB  - Neospora caninum is a protozoan which can cause abortions in caprines. However,
      information regarding the humoral immune response and the occurrence of
      reproductive disorders is scarce. This is the first study in which the kinetics
      of antibodies is studied in pregnant goats naturally infected by N. caninum, as
      well as their respective conceptuses. The subclasses of IgG (IgG1 and IgG2) were
      also evaluated in pregnant goats. Reproductive problems related to neosporosis
      (abortion and stillbirth) occurred in 15.38% of the goats. There was a
      statistically significant association between the increased titres of maternal
      IgG in the second half of the gestational period with the occurrence of
      endogenous transplacental transmission. The rate of congenital transmission was
      77%. During the gestational period of the seropositive goats, there was mainly a
      predominance of the subclass IgG2, although mixed patterns of IgG2-IgG1 and the
      IgG1 pattern were also observed. These results indicate that N. caninum is
      responsible for the occurrence of important alterations in the humoral immune
      response of naturally infected goats, and is also a potential causative agent for
      reproductive disorders in goats. The high proportion of infected conceptuses
      reinforces the suggestion that congenital infection is one of the main routes of
      parasite transmission in goats.

PMID- 23537946
TI  - Supplemental feeding drives endoparasite infection in wild boar in Western Spain.
AB  - Wildlife population management is thought to destabilize existing host-parasite
      equilibriums in opposing directions, that is, it may increase parasite success or
      host resilience once infection takes place. This process is of special importance
      for species such as the wild boar (Sus scrofa) that are managed for game purposes
      throughout much of Europe. However, little is known about how this practices
      influcences either gastrointestinal or pulmonary parasitism in the wild boar.
      Twelve hunting estates were chosen in order to study the relationship of
      management measures (feeder density, wild boar abundance, the ratio of wild boar
      per feeder and the percentage of sclerophyllous vegetation) and host factors (age
      and sex) with gastrointestinal and pulmonary parasite aggregation, richness,
      infection probability and intensity of infection. Parasitological analyses from
      300 wild boar gastrointestinal and 269 respiratory tracts were performed for this
      purpose. A set of general linear models with combinations of the explanatory
      variables was built and the model with the smallest Akaike Information Criterion
      was selected as the best. The feeder density increased gastrointestinal parasite
      traits (richness, infection probability and intensity of infection), probably due
      to the contamination of feeding sites with infective parasite forms. Pulmonary
      parasite traits, on the other hand, were only influenced by host sex and age
      class, and parasite aggregation was as expected for a wild population. Managers
      should be aware of the consequences on parasitism when implementing supplemental
      feeding in hunting estates. 

PMID- 23537947
TI  - Comparative analysis of Trichuris muris surface using conventional, low vacuum,
      environmental and field emission scanning electron microscopy.
AB  - The whipworm of the genus Trichuris Roederer, 1791, is a nematode of worldwide
      distribution and comprises species that parasitize humans and other mammals.
      Infections caused by Trichuris spp. in mammals can lead to various intestinal
      diseases of human and veterinary interest. The morphology of Trichuris spp. and
      other helminths has been mostly studied using conventional scanning electron
      microscopy of chemically fixed, dried and metal-coated specimens, although this
      kind of preparation has been shown to introduce a variety of artifacts such as
      sample shrinking, loss of secreted products and/or hiding of small structures due
      to sample coating. Low vacuum (LVSEM) and environmental scanning electron
      microscopy (ESEM) have been applied to a variety of insulator samples, also used
      in the visualization of hydrated and/or live specimens in their native state. In
      the present work, we used LVSEM and ESEM to analyze the surface of T. muris and
      analyze its interaction with the host tissue using freshly fixed or unfixed
      hydrated samples. Analysis of hydrated samples showed a set of new features on
      the surface of the parasite and the host tissue, including the presence of the
      secretory products of the bacillary glands on the surface of the parasite, and
      the presence of mucous material and eggs on the intestinal surface. Field
      emission scanning electron microscopy (FESEM) was also applied to reveal the
      detailed structure of the glandular chambers in fixed, dried and metal coated
      samples. Taken together, the results show that analysis of hydrated samples may
      provide new insights in the structural organization of the surface of helminth
      parasites and its interaction with the infected tissue, suggesting that the
      application of alternative SEM techniques may open new perspectives for analysis
      in taxonomy, morphology and host-parasite interaction fields.

PMID- 23537948
TI  - Improving the detection of anthelmintic resistance: evaluation of faecal egg
      count reduction test procedures suitable for farm routines.
AB  - The faecal egg count reduction test (FECRT) is the main method of detection of
      anthelmintic resistance (AR) in nematodes of veterinary importance. However,
      although the FECRT is standardised, the diagnostic performance of this method has
      not been fully characterised. In this survey Monte Carlo routines were used to
      simulate the estimation of faecal egg count reduction (FECR) with several FECRT
      protocols that were performed under different field and laboratory conditions.
      The goal was to determine, from a practical viewpoint, the most suitable
      protocols for farm routines and to evaluate the diagnostic performance of FECRTs
      across different parasitological scenarios with several levels of AR. The
      simulated field procedures included variations in the sample size and the
      sampling (or not) of a control group, whereas the simulated laboratory procedures
      comprised group mean individual-based vs. composite-based FECR estimations and
      variations in the egg detection threshold of the McMaster technique. For
      composite procedures, the random weight variations among individual samples and
      an increased number of McMaster chamber counts were also simulated. The results
      showed that FECRTs were moderately affected by inaccuracy but crucially affected
      by imprecision, and both parameters were clearly dependent on the parasitological
      conditions and the laboratory and field procedures used. An individual-based
      FECRT method performed without a control group was the most appropriate to
      quantify the AR, whereas a composite-based method with a control group was the
      easiest method for discriminating susceptible and resistant parasite populations.
      More interestingly, the diagnostic performance of the simulated FECRT methods was
      low for the procedures that are currently recommended by the World Association
      for the Advancement of Veterinary Parasitology (W.A.A.V.P.) and for many of the
      typical field and laboratory procedures that are currently implemented.
      Therefore, the results suggest that the diagnostic performance of the FECRT
      should be re-evaluated, and the recommendations of the W.A.A.V.P. should be
      redefined. Finally, theoretic critical conditions for FECRT procedures have been
      defined to improve future AR surveys and to allow the interpretation of FECRT
      results with the necessary caution according to the diagnostic performance
      expected for every FECRT procedure and parasitological scenario. 

PMID- 23537949
TI  - Transstadial transmission of Hepatozoon canis from larvae to nymphs of
      Rhipicephalus sanguineus.
AB  - Hepatozoon canis is an apicomplexan parasite of dogs, which is known to become
      infected by ingesting Rhipicephalus sanguineus adult ticks. To investigate the
      possibility of H. canis transovarial and transstadial transmission from larvae to
      nymphs, engorged adult female ticks were collected from a private animal shelter
      in southern Italy, where H. canis infection is highly prevalent. Female ticks
      (n=35) and egg batches were tested by PCR for H. canis. All eggs examined were
      PCR-negative whereas 88.6% of females from the environment tested positive.
      Additionally, fed larvae (n=120) from a dog naturally infected by H. canis were
      dissected at different time points post collection (i.e. 0, 10, 20 and 30 days).
      Molted nymphs dissected at 20 days post collection revealed immature oocysts
      displaying an amorphous central structure in 50% of the specimens, and oocysts
      containing sporocysts with sporozoites were found in 53.3% of the nymphs
      dissected at 30 days post collection. This study demonstrates that H. canis is
      not transmitted transovarially, but it is transmitted transstadially from larvae
      to nymphs of R. sanguineus and develops sporozoites in oocysts that may infect
      dogs. 

PMID- 23537950
TI  - Survey on the presence of Anisakis and Hysterothylacium larvae in fishes and
      squids caught in Ligurian Sea.
AB  - This study aims to investigate the occurrence of Anisakidae larvae (genera
      Anisakis and Hysterothylacium) in fishes and squids used for human nutrition and
      increase the knowledge of the distribution of Anisakidae larvae in this area of
      Mediterranean Sea. Distribution and correct identification of Anisakidae larvae
      in fish species is important for the assessment of their relative epidemiological
      role; especially when the fishes are of high commercial value and largely used in
      human nutrition. The study investigated the occurrence of Anisakidae larvae
      (genera Anisakis and Hysterothylacium) in 195 fishes owing to 22 different
      species and 60 squids (Illex coindetii) sampled in northern Ligurian Sea. A
      combination of morphological and PCR-RFLP methods have been used. A total of 177
      anisakid larvae were isolated in 42/195 (21.5%) fish of 11 species and only one
      larva in one squid. These larvae were identified morphologically as belonging to
      the genera Anisakis (36/177) or Hysterothylacium (142/177). All Anisakis larvae
      were isolated from Trachurus trachurus and were identified at species level by
      PCR-RFLP as belonging to Anisakis pegreffii. Hysterothylacium sp. in short,
      larvae presence occurred in most of examined fish species with a higher density
      in Mullus barbatus (mean intensity 5.6 larvae) and Serranus scriba (MI 5.3). 

PMID- 23537951
TI  - Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic
      transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia
      in rats.
AB  - Hyperglycemia dramatically aggravates brain infarct and hemorrhagic
      transformation (HT) after ischemic stroke. Oxidative stress and matrix
      metalloproteinases (MMPs) play an important role in the pathophysiology of HT.
      Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative
      stress and has been demonstrated to be neuroprotective in experimental stroke
      models. The present study determined whether HBO-PC would ameliorate HT by a pre
      ischemic increase of reactive oxygen species (ROS) generation, and a suppression
      of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats.
      Rats were pretreated with HBO (100% O2, 2.5 atmosphere absolutes) 1 h daily for 5
      days before MCAO. Acute hyperglycemia was induced by an injection of 50%
      dextrose. Neurological deficits, infarction volume and hemorrhagic volume were
      assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC),
      hypoxia-inducible factor-1alpha (HIF-1alpha), inhibitor 2-methoxyestradiol (2ME2)
      and activator cobalt chloride (CoCl2), and MMP inhibitor SB-3CT were
      administrated for mechanism study. The activity of MMP-2 and MMP-9, and the
      expression HIF-1alpha were measured. HBO-PC improved neurological deficits, and
      reduced hemorrhagic volume; the expression of HIF-1alpha was significantly
      decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared
      with vehicle group. Our results suggested that HBO-PC attenuated HT via
      decreasing HIF-1alpha and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO
      rats.

PMID- 23537952
TI  - Acute nigro-striatal blockade alters cortico-striatal encoding: an in vivo
      electrophysiological study.
AB  - Spreading of slow cortical rhythms into the basal ganglia (BG) is a relatively
      well-demonstrated phenomenon in the Parkinsonian state, both in humans and
      animals. Accordingly, striatal dopamine (DA) depletion, either acute or chronic,
      drives cortical-globus pallidus (GP) and cortical-substantia nigra pars
      reticulata (SNr) slow wave coherences in urethane-anesthetized rats. This paper
      investigates the striatal dynamics following acute DA depletion by tetrodotoxin
      (TTX) injection in the medial forebrain bundle (MFB) with respect to the
      transmission of slow cortical rhythms throughout the BG in more detail. The acute
      DA depletion offers the advantage of detecting electrophysiological changes
      irrespectively of chronically developing compensatory mechanisms. We observed
      that the acute blockade of the dopaminergic nigro-striatal pathway reshapes the
      firing rate and pattern of the different striatal neuron subtypes according to
      cortical activity, possibly reflecting a remodeled intrastriatal network. The
      observed alterations differ amongst striatal neuronal subtypes with the striatal
      medium spiny neurons and fast-spiking neurons being the most affected, while the
      tonically active neurons seem to be less affected. These acute changes might
      contribute to the diffusion of cortical activity to BG and the pathophysiology of
      Parkinson's disease (PD). 

PMID- 23537953
TI  - Fluorescence tomography of rapamycin-induced autophagy and cardioprotection in
      vivo.
AB  - BACKGROUND: Autophagy is a biological process during which cells digest
      organelles in their cytoplasm and recycle the constituents. The impact of
      autophagy in the heart, however, remains unclear in part because of the inability
      to noninvasively image this process in living animals. METHODS AND RESULTS: Here,
      we report the use of fluorescence molecular tomography and a cathepsin
      activatable fluorochrome to image autophagy in the heart in vivo after
      ischemia/reperfusion and rapamycin (RAP) therapy. We show that cathepsin-B
      activity in the lysosome is upregulated by RAP and that this allows the expanded
      lysosomal compartment in autophagy to be imaged in vivo with fluorescence
      molecular tomography. We further demonstrate that the delivery of diagnostic
      nanoparticles to the lysosome by endocytosis is enhanced during autophagy. The
      upregulation of autophagy by RAP was associated with a 23% reduction (P<0.05) of
      apoptosis in the area at risk and a 45% reduction in final infarct size (19.6+/
      5.6% of area at risk with RAP versus 35.9+/-9.1% of area at risk without RAP;
      P<0.05). CONCLUSIONS: The ability to perform noninvasive tomographic imaging of
      autophagy in the heart has the potential to provide valuable insights into the
      pathophysiology of autophagy, particularly its role in cardiomyocyte salvage.
      Although additional data are needed, our study supports the investigation of RAP
      therapy in patients with acute coronary syndromes.

PMID- 23537954
TI  - The CABG SYNTAX Score - an angiographic tool to grade the complexity of coronary
      disease following coronary artery bypass graft surgery: from the SYNTAX Left Main
      Angiographic (SYNTAX-LE MANS) substudy.
AB  - AIMS: The SYNTAX Score (SXscore) has established itself as an important
      prognostic tool in patients undergoing percutaneous coronary intervention (PCI).
      A limitation of the SXscore is the inability to differentiate outcomes in
      patients who have undergone prior coronary artery bypass graft (CABG) surgery.
      The CABG SXscore was devised to address this limitation. METHODS AND RESULTS: In
      the SYNTAX-LE MANS substudy 115 patients with unprotected left main coronary
      artery disease (isolated or associated with one, two or three-vessel disease)
      treated with CABG were prospectively assigned to undergo a 15-month coronary
      angiogram. An independent core laboratory analysed the baseline SXscore prior to
      CABG. The 15-month CABG SXscore was calculated by a panel of three interventional
      cardiologists. The CABG SXscore was calculated by determining the standard
      SXscore in the "native" coronary vessels ("native SXscore") and deducting points
      based on the importance of the diseased coronary artery segment (Leaman score)
      that have a functioning bypass graft anastomosed distally. Points relating to
      intrinsic coronary disease, such as bifurcation disease or calcification, remain
      unaltered. The mean 15-month CABG SXscore was significantly lower compared to the
      mean baseline SXscore (baseline SXscore 31.6, SD 13.1; 15-month CABG SXscore
      21.2, SD 11.1; p<0.001). Reproducibility analyses (kappa [k] statistics)
      indicated a substantial agreement between CABG SXscore measurements (k=0.70; 95%
      CI [0.50-0.90], p<0.001), with the points deducted to calculate the CABG SXscore
      the most reproducible measurement (k=0.74; 95% CI [0.53-0.95], p<0.001). Despite
      the limited power of the study, four-year outcome data (Kaplan-Meier curves)
      demonstrated a trend towards reduced all-cause death (9.1% vs. 1.8%, p=0.084) and
      death/CVA/MI (16.4% vs. 7.0%, p=0.126) in the low compared to the high CABG
      SXscore group. CONCLUSIONS: In this pilot study the calculation of the CABG
      SXscore appeared feasible, reproducible and may have a long-term prognostic role
      in patients with complex coronary disease undergoing surgical revascularisation.
      Validation of this new scoring methodology is required.

PMID- 23537955
TI  - Proteomic changes in different growth periods of ginseng roots.
AB  - For the first time, proteomics and biochemical variables have been employed to
      unravel the growth strategies for the different root growth periods of ginseng
      (Panax ginseng CA May., Araliaceae). Enzymatic activities and cellular contents,
      except for starch, related to defence and metabolism were significantly increased
      in the slow-growth period but decreased in the fast-growth period. Proteomic
      characterisation by two-dimensional gel electrophoresis (2DE) showed 83
      differentially expressed spots; 62 spots were up-regulated and 21 spots were down
      regulated in the slow-growth period when compared to the fast-growth period. The
      identification of these spots indicated that the major groups of differential
      proteins were associated with energy metabolism (37%) and defence (17%), which
      was consistent with the changes observed in the biochemical measurements. These
      results clearly demonstrate that ginseng stores energy during its fast-growth
      period to promote root elongation, whereas it expends energy to improve the
      synthesis of secondary metabolites and stress resistance during its slow-growth
      period. The levels of many proteins were changed during the conversion period
      from fast to slow growth, providing new insights into ginseng proteome evolution.
      The proposed hypothetical model explains the interaction of metabolic proteins
      associated with the growth strategies of ginseng. 

PMID- 23537956
TI  - [Which place for physicians in blood supply?].
AB  - Historically, blood transfusion has been divised, enhanced and organized by
      physicians. The special status of blood led to ensure that collection of blood
      and its components were placed under the supervision of a physician. Throughout
      its history, blood transfusion organization in France has established an
      exclusive exercise of the collection of blood and its components entrusted to
      doctors, thus creating the concept of "medicine of donation". This view is
      changing, and programmed exercise of this activity by nurses led to question
      about this profession perimeter, its necessary evolution, and finally about the
      place of physicians in blood supply.

PMID- 23537957
TI  - Genomic sequence analysis of the United States infectious laryngotracheitis
      vaccine strains chicken embryo origin (CEO) and tissue culture origin (TCO).
AB  - The genomic sequences of low and high passages of the United States infectious
      laryngotracheitis (ILT) vaccine strains CEO and TCO were determined using hybrid
      next generation sequencing in order to define genomic changes associated with
      attenuation and reversion to virulence. Phylogenetic analysis of available full
      genomes grouped strains into three major clades: TCO, CEO, and Australian.
      Comparative genomics revealed that TCO attenuation is likely the result of an ORF
      C truncation. Genes involved in attenuation are generally clade-specific, however
      four genes ORF C, UL27, UL28 and UL39 commonly contained various mutations across
      the CEO and TCO lineages. The Thr644 mutation in the UL27 gene encoding
      glycoprotein B was identified in all virulent US strains. The US10 gene was
      identified as a potential virulence factor for the TCO revertant 81658. The UL41
      gene was responsible for the robust gain in virulence of CEO-Fowl
      Laryngotracheitis((r)) after 20 passages in chickens.

PMID- 23537958
TI  - A single amino acid V4I substitution in VP1 attenuates virulence of very virulent
      infectious bursal disease virus (vvIBDV) in SPF chickens and increases
      replication in CEF cells.
AB  - Infectious bursal disease virus (IBDV) is a birnavirus that causes
      immunosuppressive disease in chickens. The emergence of very virulent IBDV
      (vvIBDV) has brought new challenges for this disease. The molecular determinants
      for the high pathogenicity of vvIBDV are not fully understood. Previous studies
      focused mostly on the VP2 protein on segment A, but recent evidence suggests that
      segment B also plays an important role. Previously we identified eight amino acid
      changes in the VP1 protein of vvIBDV. In this study, we investigated effect of
      amino acids substitutions in VP1 on viral replication and pathogenicity. We
      identified a Valine to Isoleucine substitution at amino acid position 4 (V4I) of
      VP1 that attenuates viral pathogenicity and reduces viral replication in SPF
      chickens but increases viral replication in CEF cells. This study confirms that
      VP1 of segment B play an important role in viral replication and pathogenicity of
      vvIBDV.

PMID- 23537959
TI  - HIV 2-long terminal repeat circular DNA is stable in primary CD4+T Cells.
AB  - Treatment resistant latent reservoirs remain a barrier to cure HIV, but the
      maintenance and properties of these reservoirs are not completely understood. 2
      LTR circular HIV DNA has been used to assess ongoing viral replication in HAART
      treated patients. However, the half-life of this DNA form is still debated with
      conflicting in vivo and in vitro data. Prior in vitro studies have focused on
      cell lines or short lived activated cells in cultures of brief duration, while in
      vivo studies have the added complications of cell migration, division, and death.
      Therefore, we monitored the stability of 2-LTR circles in primary CD4+T cells in
      a month long culture and compared it to the stability of integrated HIV DNA and T
      cell receptor excision circles (TRECs), another circular DNA form that is thought
      to be stable. We found that 2-LTRs, along with TRECs, were stable, suggesting 2
      LTRs do not necessarily indicate ongoing replication.

PMID- 23537960
TI  - Risk scores in acute coronary syndrome and percutaneous coronary intervention: a
      review.
AB  - Patients with acute coronary syndrome (ACS) need to be risk stratified to deliver
      the most appropriate therapy. The GRACE and TIMI risk scores have penetrated
      contemporary guidelines with the former most commonly used in clinical practice.
      However, ACS prediction models need to be re-evaluated in contemporary practice
      with evolving diagnostic and treatment options. Moreover, the increased
      availability of percutaneous coronary intervention (PCI) as a treatment option
      for ACS combined with an expanding case mix and emphasis on quality control have
      triggered the creation of PCI specific prognostic models. These allow clinicians
      and patients to have an understanding of expected outcomes following PCI by
      predicting outcomes in-hospital to 5 years following intervention. The aim of
      this review is to evaluate the most recognized and studied ACS/PCI risk models,
      focusing on their strengths and limitations, and to assess the need for more
      robust tools to predict outcomes in a period of constantly advancing technologies
      and changing patient demographics.

PMID- 23537961
TI  - Association of time to reperfusion with left ventricular function and heart
      failure in patients with acute myocardial infarction treated with primary
      percutaneous coronary intervention: a systematic review.
AB  - BACKGROUND: Shorter time to reperfusion is associated with a significant
      reduction in mortality; however, its association with heart failure (HF) is not
      clearly documented. We conducted a systematic review to examine the association
      between time to reperfusion and incident HF and/or left ventricular dysfunction.
      METHODS: MEDLINE/OVID, EMBASE, Cochrane Library, and Web of Science databases
      were searched from January 1974 to May 2012 for studies that reported the
      association between time to reperfusion and incident HF or left ventricular
      ejection fraction (LVEF) in patients undergoing primary percutaneous coronary
      intervention. RESULTS: Of 362 nonduplicate abstracts, 71 studies were selected
      for full-text review. Thirty-three studies were included in the final review, of
      which 16 were single-center studies, 7 were population-based studies, 7 were
      subanalyses from randomized controlled trials, and 3 were based on national
      samples. The pooled data demonstrate that every 1-hour delay in time to
      reperfusion is associated with a 4% to 12% increased risk of new-onset HF and a
      4% relative increase in the risk of incident HF during follow-up. Early
      reperfusion was associated with a 2% to 8% greater LVEF before discharge and a 3%
      to 12% larger improvement in absolute LVEF at follow-up compared with the index
      admission. CONCLUSIONS: This systematic review presents evidence that longer time
      to reperfusion is not only associated with worsened left ventricular systolic
      function and new-onset HF at the time of index admission, but also with increased
      risk of HF and reduced improvement in left ventricular systolic function during
      follow-up.

PMID- 23537963
TI  - Assessment of drug-induced increases in blood pressure during drug development:
      report from the Cardiac Safety Research Consortium.
AB  - This White Paper, prepared by members of the Cardiac Safety Research Consortium,
      discusses several important issues regarding the evaluation of blood pressure
      (BP) responses to drugs being developed for indications not of a direct
      cardiovascular (CV) nature. A wide range of drugs are associated with off-target
      BP increases, and both scientific attention and regulatory attention to this
      topic are increasing. The article provides a detailed summary of scientific
      discussions at a Cardiac Safety Research Consortium-sponsored Think Tank held on
      July 18, 2012, with the intention of moving toward consensus on how to most
      informatively collect and analyze BP data throughout clinical drug development to
      prospectively identify unacceptable CV risk and evaluate the benefit-risk
      relationship. The overall focus in on non-CV drugs, although many of the points
      also pertain to CV drugs. Brief consideration of how clinical assessment can be
      informed by nonclinical investigation is also outlined. These discussions present
      current thinking and suggestions for furthering our knowledge and understanding
      of off-target drug-induced BP increases and do not represent regulatory guidance.

PMID- 23537962
TI  - Obstructive sleep apnea and cardiovascular disease in blacks: a call to action
      from the Association of Black Cardiologists.
AB  - Obstructive sleep apnea (OSA) has emerged as a new and important risk factor for
      cardiovascular disease (CVD). Over the last decade, epidemiologic and clinical
      research has consistently supported the association of OSA with increased
      cardiovascular (CV) morbidity and mortality. Such evidence prompted the American
      Heart Association to issue a scientific statement describing the need to
      recognize OSA as an important target for therapy in reducing CV risk. Emerging
      facts suggest that marked racial differences exist in the association of OSA with
      CVD. Although both conditions are more prevalent in blacks, almost all National
      Institutes of Health-funded research projects evaluating the relationship between
      OSA and CV risk have been conducted in predominantly white populations. There is
      an urgent need for research studies investigating the CV impact of OSA among high
      risk minorities, especially blacks. This article first examines the evidence
      supporting the association between OSA and CVD and reviews the influence of
      ethnic/racial differences on this association. Public health implications of OSA
      and future directions, especially regarding minority populations, are discussed.

PMID- 23537964
TI  - The evaluation and management of drug effects on cardiac conduction (PR and QRS
      intervals) in clinical development.
AB  - Recent advances in electrocardiographic monitoring and waveform analysis have
      significantly improved the ability to detect drug-induced changes in cardiac
      repolarization manifested as changes in the QT/corrected QT interval. These
      advances have also improved the ability to detect drug-induced changes in cardiac
      conduction. This White Paper summarizes current opinion, reached by consensus
      among experts at the Cardiac Safety Research Consortium, on the assessment of
      electrocardiogram-based safety measurements of the PR and QRS intervals,
      representing atrioventricular and ventricular conduction, respectively, during
      drug development.

PMID- 23537965
TI  - Telemedicine cardiovascular risk reduction in veterans.
AB  - BACKGROUND: Patients with co-occurrence of hypertension, hyperlipidemia, and
      diabetes have an increased risk of cardiovascular disease (CVD) events.
      Comprehensive programs addressing both tailored patient self-management and
      pharmacotherapy are needed to address barriers to optimal cardiovascular risk
      reduction. We are examining a Clinical pharmacy specialist-, telephone
      administered intervention, relying on home monitoring, with a goal of providing
      tailored medication and behavioral intervention to Veterans with CVD risk.
      METHODS: Randomized controlled trial including patients with hypertension (blood
      pressure >150/100 mm Hg) or elevated low density liporotein (>130 mg/dL).
      Longitudinal changes in CVD risk profile and improvement in health behaviors over
      time will be examined. CONCLUSION: Given the national prevalence of CVD and the
      dismal rates of risk factor control, intensive but easily disseminated
      interventions are required to treat this epidemic. This study will be an
      important step in testing the effectiveness of a behavioral and medication
      intervention to improve CVD control among Veterans.

PMID- 23537966
TI  - Rationale and design of the EMBRACE STEMI study: a phase 2a, randomized, double
      blind, placebo-controlled trial to evaluate the safety, tolerability and efficacy
      of intravenous Bendavia on reperfusion injury in patients treated with standard
      therapy including primary percutaneous coronary intervention and stenting for ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Although significant efforts have been made to improve ST-segment
      elevation myocardial infarction (STEMI) outcomes by reducing symptom-onset-to
      reperfusion times, strategies to decrease the clinical impact of ischemic
      reperfusion injury have demonstrated limited success. Bendavia, an intravenously
      administered mitochondrial targeting peptide, has been shown to reduce myocardial
      infarct size and attenuate coronary no-reflow in experimental modelswhen given
      before reperfusion. DESIGN: The EMBRACE STEMI study is a phase 2a, randomized,
      double-blind, placebo-controlled trial enrolling 300 patients with a first-time
      anterior STEMI and an occluded proximal or mid-left anterior descending artery
      undergoing primary percutaneous coronary intervention (PCI) within 4 hours of
      symptom onset. Patients will be randomized to receive either Bendavia at 0.05
      mg/kg per hour or an identically appearing placebo administered as an intravenous
      infusion at 60 mL/h. The primary end point is infarct size measured by the area
      under the creatine kinase-MB enzyme curve calculated from measurements from the
      central clinical chemistry laboratory obtained over the initial 72 hours after
      the primary PCI procedure, and the major secondary end point is infarct size
      calculated by the volume of infarcted myocardium (late contrast gadolinium
      enhancement) on the day 4+/-1 cardiac magnetic resonance imaging. SUMMARY:
      EMBRACE-STEMI is testing the hypothesis that Bendavia, in conjunction with
      standard-of-care therapy, is superior to placebo for the reduction of myocardial
      infarction size among patients with first time, acute, anterior wall STEMI who
      undergo successful reperfusion with primary PCI and stenting.

PMID- 23537967
TI  - Ambulance or in-catheterization laboratory administration of ticagrelor for
      primary percutaneous coronary intervention for ST-segment elevation myocardial
      infarction: rationale and design of the randomized, double-blind Administration
      of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial
      Infarction to open the Coronary artery (ATLANTIC) study.
AB  - Primary percutaneous coronary intervention (PCI) is the treatment of choice for
      patients presenting with acute ST-segment elevation myocardial infarction
      (STEMI). However, if catheterization facilities are not immediately available,
      the effectiveness of PCI can be affected by delays in transfer. Evidence suggests
      that antiplatelet therapy administered early, preferably in the ambulance during
      transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet
      P2Y12 receptor inhibitor, is indicated for the management of patients with acute
      coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a
      30-day international, randomized, parallel-group, placebo-controlled study in
      male and female patients (aged >=18 years) who are diagnosed as having STEMI,
      with intended primary PCI. In total, 1770 patients will be randomized immediately
      after diagnosis to prehospital administration of ticagrelor 180 mg followed by
      matching placebo administered in hospital, or prehospital administration of
      placebo followed by ticagrelor 180 mg administered in hospital. All patients will
      then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is
      the percentage of patients reaching thrombolysis in myocardial infarction flow
      grade 3 in the infarct-related artery at initial angiography or achieving >=70%
      ST-segment elevation resolution pre-PCI. The primary safety end point is major,
      life-threatening, or minor bleeding after ticagrelor administration. The results
      of this study may have an impact on future recommendations for treatment for
      patients with STEMI.

PMID- 23537969
TI  - The PARACHUTE IV trial design and rationale: percutaneous ventricular restoration
      using the parachute device in patients with ischemic heart failure and dilated
      left ventricles.
AB  - BACKGROUND: Left ventricle (LV) remodeling after anterior wall myocardial
      infarction leads to increased LV volumes, myocardial stress, and, ultimately,
      heart failure (HF). Patients have high morbidity and mortality risk, and
      treatment remains limited. Percutaneous ventricular restoration (PVR) therapy
      using the Parachute device, a fluoropolymer membrane stretched over a nitinol
      conical frame, is a novel approach to partition off the damaged myocardium. In
      the European and United States PARACHUTE feasibility trials, the observed rates
      of death or rehospitalization for HF were <17% at 12 months. These data compare
      favorably with historical data and support the need of a randomized trial to
      determine the clinical efficacy of PVR on outcomes for patients with ischemic HF.
      OBJECTIVE: To determine the safety and efficacy of PVR utilizing a LV
      partitioning device, Parachute, in a randomized clinical trial compared with
      optimal medical therapy. METHODS: This US pivotal trial is approved by the Food
      and Drug Administration (ClinicalTrials.gov Identifier: NCT01286116) and will
      randomly assign (1:1) 478 patients with New York Heart Association class III-IV
      ischemic HF, akinetic or dyskinetic LV wall abnormality, and ejection fraction
      between 15% and 35% to optimal medical therapy (control) versus Parachute device
      implantation in approximately 65 hospitals. The primary endpoint is death or
      rehospitalization for worsening HF. Sample size calculation assumes constant
      hazards and follow-up >=12 months using an event-driven trial design.
      CONCLUSIONS: We reported the rational and design of the first multicenter
      randomized trial to test the efficacy of PVR using the Parachute device to treat
      patients with ischemic HF and dilated LV.

PMID- 23537968
TI  - Rationale and design of the ATTRACT Study: a multicenter randomized trial to
      evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of
      postthrombotic syndrome in patients with proximal deep vein thrombosis.
AB  - BACKGROUND: Current standard therapy for patients with acute proximal deep vein
      thrombosis (DVT) consists of anticoagulant therapy and graduated elastic
      compression stockings. Despite use of this strategy, the postthrombotic syndrome
      (PTS) develops frequently, causes substantial patient disability, and impairs
      quality of life. Pharmacomechanical catheter-directed thrombolysis (PCDT), which
      rapidly removes acute venous thrombus, may reduce the frequency of PTS. However,
      this hypothesis has not been tested in a large multicenter randomized trial.
      STUDY DESIGN: The ATTRACT Study is an ongoing National Institutes of Health
      sponsored, Phase III, multicenter, randomized, open-label, assessor-blinded,
      parallel two-arm, controlled clinical trial. Approximately 692 patients with
      acute proximal DVT involving the femoral, common femoral, and/or iliac vein are
      being randomized to receive PCDT + standard therapy versus standard therapy
      alone. The primary study hypothesis is that PCDT will reduce the proportion of
      patients who develop PTS within 2 years by one-third, assessed using the Villalta
      Scale. Secondary outcomes include safety, general and venous disease-specific
      quality of life, relief of early pain and swelling, and cost-effectiveness.
      CONCLUSION: ATTRACT will determine if PCDT should be routinely used to prevent
      PTS in patients with symptomatic proximal DVT above the popliteal vein.

PMID- 23537970
TI  - Sex-related effectiveness of bivalirudin versus abciximab and heparin in non-ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Female sex independently predicts bleeding risk after percutaneous
      coronary intervention (PCI). Bivalirudin is safer than abciximab plus heparin in
      patients with non-ST-segment elevation myocardial infarction (NSTEMI). Thus, a
      greater benefit of bivalirudin in women would be expected. METHODS: We performed
      a sex-based analysis of the patients with NSTEMI (n = 1,721, 399 women) enrolled
      in the ISAR-REACT 4 trial and randomized to receive bivalirudin or abciximab plus
      heparin. Main outcome was a 30-day composite of death, large recurrent myocardial
      infarction, urgent target vessel revascularization, or major bleeding. Secondary
      outcome was 1-year composite of death, myocardial infarction, or target vessel
      revascularization. RESULTS: No difference in the main outcome was observed in
      groups with bivalirudin or abciximab plus heparin: 12.6% versus 15.5% (hazard
      ratio [HR] 0.81, 95% CI 0.48-1.37) among women and 10.6% versus 9.5% (HR 1.12,
      95% CI 0.77-1.64) among men. Major bleeding occurred in 4.5% in the bivalirudin
      group versus 7.5% in the abciximab plus heparin group (HR 0.60, 95% CI 0.26-1.39)
      among women and 2.0% versus 3.8% (HR 0.52, 0.27-1.02) among men. At 1 year, the
      secondary outcome was observed in 24.1% in the bivalirudin group versus 28.7% in
      the abciximab plus heparin group among women, HR of 0.80 (95% CI 0.55-1.17), and
      in 20.6% and 19.0%, respectively, HR of 1.10 (95% CI 0.86-1.40) among men.
      CONCLUSION: Despite a higher peri-PCI bleeding risk in women, bivalirudin is as
      effective as and safer than abciximab plus heparin in women and men with NSTEMI
      undergoing PCI.

PMID- 23537971
TI  - The association of fetal cerebrovascular resistance with early neurodevelopment
      in single ventricle congenital heart disease.
AB  - BACKGROUND: Children with congenital heart disease are at risk for impaired
      neurodevelopment (ND). We investigated the association of fetal cerebrovascular
      resistance with ND in patients with single ventricle lesions. METHODS: In the
      Single Ventricle Reconstruction (SVR) and Infant Single Ventricle trials, 14
      month ND was assessed using the Bayley Scales of Infant Development II. We
      investigated associations between ND scores and fetal middle cerebral artery
      pulsatility index (MCA-PI) z-scores, a Doppler-derived estimate of
      cerebrovascular resistance in a subset of those infants. RESULTS:
      Neurodevelopment assessments were performed at age 14.3 +/- 1 months in 170 (74%)
      of 230 Infant Single Ventricle and 321 (58%) of 555 SVR subjects. Fetal
      echocardiographic data were available in 119 subjects, 72 (61%) of which had ND
      testing. Mean Psychomotor Development Index (PDI) (76 +/- 20) and Mental
      Development Index (MDI) (89 +/- 17) scores were lower than normative means (100
      +/- 15, P < .001). Mean MCA-PI z-score was -0.95 +/- 1.52. Middle cerebral artery
      pulsatility index z-score correlated negatively with PDI (r = -0.27, P = .02) but
      was not associated with MDI. When MCA-PI z-score was added to a multivariable
      model controlling for factors identified in the SVR trial to predict PDI, the
      percentage of explained variation increased from 23% to 30%, and MCA-PI z-score
      remained an independent predictor (r = -3.864, P = .03). Middle cerebral artery
      pulsatility index z-score was not an independent predictor in a model adjusting
      for site. CONCLUSIONS: Among fetuses with single ventricle anomalies, lower
      cerebrovascular resistance was associated with higher ND scores. This
      relationship is opposite to that observed with advanced intrauterine growth
      retardation and may represent a unique ability of these congenital heart disease
      fetuses to compensate for diminished cerebral oxygen delivery.

PMID- 23537972
TI  - Relation of right ventricular mechanics to exercise tolerance in children after
      tetralogy of Fallot repair.
AB  - BACKGROUND: Progressive right ventricular (RV) dysfunction and exercise
      intolerance are common problems after tetralogy of Fallot (TOF) repair. We
      investigated RV myocardial deformation and dyssynchrony in children after TOF
      repair and their association with exercise capacity. METHODS: Asymptomatic
      children after TOF repair were investigated by 2-dimensional speckle tracking
      echocardiography, magnetic resonance, and metabolic exercise study. Patients with
      RV outflow obstruction were excluded. Peak RV longitudinal strain and strain rate
      (SR) and dyssynchrony (RV intraventricular delay) were compared with healthy
      controls. Associations between RV strain, dyssynchrony, and exercise capacity
      were analyzed. RESULTS: Thirty-nine (81%) of 48 TOF patients and 40 healthy
      controls had adequate RV strain imaging. The TOF patients had moderately dilated
      RVs and normal RV ejection fraction. Right ventricular peak systolic strain (
      23.2% +/- 5.1% vs -28.5% +/- 8.5%, P < .001) and SR (-1.46 +/- 0.68 vs -2.1 +/-
      0.8, P < .001) were reduced in TOF patients compared with controls. Right
      ventricular intraventricular delay was higher in TOF patients (146.0 +/- 159 vs
      71.0 +/- 92 milliseconds, P = .008). Decreased RV strain and SR were associated
      with increased RV dyssynchrony (strain parameter estimate [PE] 6.31 [2.30], P =
      .007; SR [PE] 11.32 [3.84], P = .004). Increased RV-left ventricular delay was
      associated with prolonged QRS duration (PE 0.13 [0.058], P = .03) and reduced RV
      ejection fraction (PE -2.95 [1.275], P = .02). Reduced RV peak SR was associated
      with decreased exercise peak oxygen uptake (PE 0.14 [0.07], P = .04).
      CONCLUSIONS: After repair of TOF, asymptomatic children have reduced RV
      deformation in association with RV dyssynchrony and reduced exercise tolerance.

PMID- 23537973
TI  - Matrix metalloproteinases 2 and 9 as diagnostic markers in the progression to
      Chagas cardiomyopathy.
AB  - BACKGROUND: Infection with the Trypanosoma cruzi parasite is endemic in parts of
      Central and South America. Approximately 30% of those infected develop Chagas
      cardiomyopathy, the most common cause of heart failure in this region. No
      suitable biomarker is available that reflects the evolution of the disease.
      Although there is substantial evidence of a strong inflammatory reaction
      following infection that could activate matrix metalloproteinases (MMPs), their
      role in the development of Chagas cardiomyopathy is unknown. METHODS: A cross
      sectional study was conducted in Bucaramanga, Colombia, from 2002 to 2006,
      including 144 patients at different stages of Chagas disease and 44 control
      patients. The potential enzyme activities of MMP-2 and MMP-9 in plasma samples
      were determined by gelatin zymography. Clinical data including T cruzi serology,
      electrocardiograms, and echocardiograms were recorded for all patients. RESULTS:
      Densitometric analysis of potential enzyme activities in plasma samples showed a
      significant increase of 72-kd MMP-2 (P < .001) and 92-kd MMP-9 (P < .001) in T
      cruzi seropositive patients compared with control subjects. Matrix
      metalloproteinase 9 showed significantly increased activity in patients with
      abnormal electrocardiogram (P < .004) and with dilated cardiomyopathy compared (P
      < .001) with controls. Analysis of the MMP-2 and MMP-9 results in relation to
      clinical data revealed that abnormal heart relaxation correlated positively with
      high MMP-2 levels in patients with dilated cardiomyopathy (r = 0.75, P < .01).
      CONCLUSIONS: Plasma MMP-2 and MMP-9 both appear to be useful biomarkers for
      detecting the advent and progression of cardiomyopathy in T cruzi-infected
      individuals.

PMID- 23537974
TI  - Admission heart rate and in-hospital outcomes in patients hospitalized for heart
      failure in sinus rhythm and in atrial fibrillation.
AB  - BACKGROUND: Prior studies have suggested an association between higher heart rate
      and higher mortality, particularly in chronic heart failure (HF). Whether this
      relationship holds true in patients hospitalized with HF and differs between
      patients in sinus rhythm (SR) and atrial fibrillation (AF) has not been well
      studied. METHODS: We examined 145,221 admissions for HF from 295 hospitals
      enrolled in Get With The Guidelines-Heart Failure from January 2005 through
      September 2011. The associations of admission heart rate with in-hospital
      outcomes were evaluated overall and by heart rhythm. RESULTS: Patients presenting
      at higher heart rate tended to be younger and have less comorbidities. In
      hospital mortality had a J-shaped relationship with heart rate, with the lowest
      mortality rate associated with heart rates between 70 and 75. However, the
      relationship differed between patients presenting in SR and AF: at heart rates
      above 100, the mortality curve for AF plateaued, whereas that for SR continued to
      rise. Higher heart rate was independently associated with higher mortality (SR
      adjusted OR 1.21, 95% CI 1.15-1.28 per 10 beat per minute increase in heart rate
      between 70-105; AF adjusted OR 1.20, 95% CI 1.14-1.27). Findings were similar
      when stratifying patients by ischemic etiology, diabetes, ejection fraction,
      blood pressure, and beta-blocker use. CONCLUSIONS: Higher admission heart rate is
      independently associated with worse outcomes in patients admitted for HF,
      including those in SR and AF. Whether early heart rate reduction improves
      outcomes in patients hospitalized with HF is worthy of investigation.

PMID- 23537975
TI  - Iron deficiency in chronic heart failure: an international pooled analysis.
AB  - BACKGROUND: Iron deficiency (ID) is an emerging problem in patients with chronic
      heart failure (HF) and can be a potential therapeutic target. However, not much
      is known about the prevalence, predictors, and prognosis of ID in patients with
      chronic HF. METHODS: In an international pooled cohort comprising 1,506 patients
      with chronic HF, we studied the clinical associates of ID and its prognostic
      consequences. RESULTS: Iron deficiency (defined as a ferritin level <100 MUg/L or
      ferritin 100-299 MUg/L with a transferrin saturation <20%) was present in 753
      patients (50%). Anemic patients were more often iron deficient than nonanemic
      patients (61.2% vs 45.6%, P < .001). Other independent predictors of ID were
      higher New York Heart Association class, higher N-terminal pro-brain-type
      natriuretic peptide levels, lower mean corpuscular volume levels, and female sex
      (all P < .05). During follow-up (median 1.92 years, interquartile range 1.18-3.26
      years), 440 patients died (29.2%). Kaplan-Meier survival analysis revealed ID as
      a strong predictor for mortality (log rank chi(2) 10.2, P = .001). In
      multivariable hazard models, ID (but not anemia) remained a strong and
      independent predictor of mortality (hazard ratio 1.42, 95% confidence interval
      1.14-1.77, P = .002). Finally, the presence of ID significantly enhanced risk
      classification and integrated discrimination improvement when added to a
      prediction model with established risk factors. CONCLUSIONS: Iron deficiency is
      common in patients with chronic HF, relates to disease severity, and is a strong
      and independent predictor of outcome. In this study, ID appears to have greater
      predictive power than anemia.

PMID- 23537976
TI  - Radial versus femoral access, bleeding and ischemic events in patients with non
      ST-segment elevation acute coronary syndrome managed with an invasive strategy.
AB  - BACKGROUND: Bleeding is a major limitation of antithrombotic therapy among
      invasively managed non-ST-segment elevation acute coronary syndromes (NSTE-ACS)
      patients; therefore, we examined the use of radial access and its association
      with outcomes among NSTE-ACS patients. METHODS: Clinical characteristics and
      geographic variation in radial access were examined, as well as its association
      with bleeding, red blood cell transfusion and ischemic outcomes (96-hour
      death/myocardial infarction/recurrent ischemic/thrombotic bailout; 30-day
      death/myocardial infarction; 1-year death) in the EARLY versus delayed,
      provisional eptifibatide in acute coronary syndromes trial. RESULTS: Of 9126
      patients, 13.5% underwent radial-access catheterization. Female sex, age, weight,
      and prior revascularization were inversely associated with radial access, and its
      use varied widely by country (2%-97%). There were fewer GUSTO severe/moderate
      bleeds and red blood cell transfusions in the radial access group; however, it
      was attenuated after adjustment (odds ratio 0.73, 95% confidence intervals [CI]
      [0.50-1.06], P = .094 and 1.00 [0.71-1.40] P = .991). Ischemic outcomes did not
      differ by access site. CONCLUSIONS: In this post hoc analysis of a large clinical
      trial, there was significant international variation in use of radial access for
      NSTE-ACS patients undergoing invasive management, and it was preferentially used
      in those at lower risk for bleeding. Radial approach was not associated with a
      significant reduction in either bleeding or ischemic outcomes. Further study is
      needed to determine whether wider application of radial approach to acute
      coronary syndrome patients at high risk for bleeding improves overall outcomes.

PMID- 23537977
TI  - Bare-metal stenting of large coronary arteries in ST-elevation myocardial
      infarction is associated with low rates of target vessel revascularization.
AB  - BACKGROUND: During percutaneous coronary intervention (PCI) performed in the
      emergent setting of ST-segment elevation myocardial infarction (STEMI),
      uncertainty about patients' ability to comply with 12 months dual antiplatelet
      therapy after drug-eluting stenting is common, and thus, selective bare-metal
      stent (BMS) deployment could be an attractive strategy if this achieved low
      target vessel revascularization (TVR) rates in large infarct-related arteries
      (IRAs) (>=3.5 mm). METHODS AND RESULTS: To evaluate this hypothesis, among 1,282
      patients with STEMI who underwent PCI during their initial hospitalization, we
      studied 1,059 patients (83%) who received BMS, of whom 512 (48%) had large IRAs
      >=3.5 mm in diameter, 333 (31%) had IRAs 3 to 3.49 mm, and 214 (20%) had IRAs <3
      mm. At 1 year, TVR rate in patients with BMS was 5.8% (2.2% with large BMS [>=3.5
      mm], 9.2% with BMS 3-3.49 mm [intermediate], and 9.0% with BMS <3.0 mm [small], P
      < .001). The rates of death/reinfarction among patients with large BMS compared
      with intermediate BMS or small BMS were lower (6.6% vs 11.7% vs 9.0%, P = .042).
      Among patients who received BMS, the independent predictors of TVR at 1 year were
      the following: vessel diameter <3.5 mm (odds ratio [OR] 4.39 [95% CI 2.24-8.60],
      P < .001), proximal left anterior descending coronary artery lesions (OR 1.89
      [95% CI 1.08-3.31], P = .027), hypertension (OR 2.01 [95% CI 1.17-3.438], P =
      .011), and prior PCI (OR 3.46 [95% CI 1.21-9.85], P = .02). The predictors of
      death/myocardial infarction at 1 year were pre-PCI cardiogenic shock (OR 8.16
      [95% CI 4.16-16.01], P < .001), age >=65 years (OR 2.63 [95% CI 1.58-4.39], P <
      .001), left anterior descending coronary artery culprit lesions (OR 1.95 [95% CI
      1.19-3.21], P = .008), female gender (OR 1.93 [95% CI 1.12-3.32], P = .019), and
      American College of Cardiology/American Heart Association lesion classes B2 and C
      (OR 2.17 [95% CI 1.10-4.27], P = .026). CONCLUSION: Bare-metal stent deployment
      in STEMI patients with IRAs >=3.5 mm was associated with low rates of TVR. Their
      use in this setting warrants comparison with second-generation drug-eluting
      stenting deployment in future randomized clinical trials.

PMID- 23537978
TI  - Use of the contrast volume or grams of iodine-to-creatinine clearance ratio to
      predict mortality after percutaneous coronary intervention.
AB  - BACKGROUND: Few studies have assessed the predictive value of the ratio of the
      contrast media volume or grams of iodine to the creatinine clearance (V/CrCl or g
      I/CrCl, respectively) for the risk of contrast-induced nephropathy (CIN) and
      mortality after percutaneous coronary intervention (PCI). METHODS: The
      association between V/CrCl and mortality was prospectively evaluated in 1,135
      consecutive patients undergoing PCI. Cox regression models were used to adjust
      for the V/CrCl ratio and other confounding factors for risk of death within 1
      year. RESULTS: Fifty-five patients (4.84%) developed CIN. The 1-year mortality
      was higher in patients with a V/CrCl ratio >2.62 (g-I/CrCl >0.97) than in others
      (4.44% vs 0.40%; P < .001). After adjusting for other risk factors, the 1-year
      mortality risk remained associated with increased V/CrCl ratio. The risk of death
      was significant for V/CrCl >2.62 (adjusted risk ratio [RR] for death 2.605, 95%
      CI 1.040-6.529, P = .041), V/CrCl >3.0 (g-I/CrCl >1.11) (adjusted RR 4.338, 95%
      CI 1.689-11.142, P = .002), and V/CrCl >3.7 (g-I/CrCl >1.37) (adjusted RR 2.557,
      95% CI 1.162-5.627, P = .002). CONCLUSION: The data further support the
      prognostic significance of calculating the V/CrCl ratio to predict the relative
      maximum contrast volume during PCI. Use of a contrast dose determined based on
      the estimated renal function with a planned V/CrCl ratio <3.7 (g-I/CrCl <1.37)
      and preferably <2.62 (g-I/CrCl <0.97) might be valuable in reducing the risks of
      CIN and even death after PCI.

PMID- 23537979
TI  - Discordant effects of rosiglitazone on novel inflammatory biomarkers.
AB  - BACKGROUND: Although rosiglitazone favorably affects myriad intermediate markers
      of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We
      analyzed the effects of rosiglitazone on a panel of 8 novel circulating
      biomarkers, 4 of which are independently associated with atherosclerosis:
      lymphotoxin beta receptor, peptidoglycan recognition protein 1, chemokine ligand
      23, and soluble receptor for advanced glycation end products (sRAGE) as well as
      on high-sensitivity C-reactive protein (hs-CRP). METHODS: Blood samples were
      analyzed at baseline and after 6 months of study treatment from subjects with
      type 2 diabetes with or at high risk for coronary artery disease in a randomized
      trial comparing rosiglitazone versus placebo. RESULTS: Data from 111 subjects
      (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were
      women, and 66% were nonwhite. Compared with baseline values, rosiglitazone
      adversely affected levels of lymphotoxin beta receptor (1.7 vs 2.4 ng/mL, P =
      .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and
      chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels
      of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003)
      and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with
      rosiglitazone in the other biomarkers. In the placebo group, change was observed
      only for sRAGE (1.0 vs 1.1 ng/mL, P = .046). CONCLUSION: Rosiglitazone adversely
      affected 3 novel biomarkers and favorably affected a fourth previously associated
      with atherosclerosis while improving hs-CRP, as has previously been shown.
      Whether these complex effects on circulating inflammatory biomarkers contribute
      to the signal of increased MI risk with rosiglitazone and whether pioglitazone
      has similar effects warrant further investigation.

PMID- 23537980
TI  - Managing hypertension in urban underserved subjects using telemedicine--a
      clinical trial.
AB  - BACKGROUND: We evaluated an Internet- and telephone-based telemedicine system for
      reducing blood pressure (BP) in underserved subjects with hypertension. METHODS:
      A total of 241 patients with systolic BP >=140 mm Hg were randomized to usual
      care (C; n = 121) or telemedicine (T; n = 120). The T group reported BP, heart
      rate, weight, steps/day, and tobacco use twice weekly. The primary outcome was BP
      control at 6 months. RESULTS: Average age was 59.6 years, average body mass index
      was 33.7 kg/m(2), 79% were female, 81% were African American, 15% were white, 53%
      were at or below the federal poverty level, 18% were smokers, and 32% had
      diabetes. Six-month follow-up was achieved in 206 subjects (C: 107, T: 99). Goal
      BP was achieved in 52.3% in C and 54.5% in T (P = .43). Systolic BP change (C: 
      13.9 mm Hg, T: -18.2; P = .118) was similar in both groups. Subjects in the T
      group reported BP 7.7 +/- 6.9 d/mo. Results were not affected by age, sex,
      ethnicity, education, or income. In nondiabetic T subjects, goal BP was achieved
      in 58.2% compared with 45.2% of diabetic T subjects (P = .024). Nondiabetic T
      subjects demonstrated a greater reduction in systolic BP (T: -19 +/- 20 mm Hg, C:
      -12 +/- 19 mm Hg; P = .037). No difference in BP response between C and T was
      noted in patients with diabetes. CONCLUSION: In hypertensive subjects, engagement
      in a system of care with or without telemedicine resulted in significant BP
      reduction. Telemedicine for nondiabetic patients resulted in a greater reduction
      in systolic BP compared with usual care. Telemedicine may be a useful tool for
      managing hypertension particularly among nondiabetic subjects.

PMID- 23537981
TI  - Rate versus rhythm control for management of atrial fibrillation in clinical
      practice: results from the Outcomes Registry for Better Informed Treatment of
      Atrial Fibrillation (ORBIT-AF) registry.
AB  - BACKGROUND: All patients with atrial fibrillation (AF) require optimization of
      their ventricular rate. Factors leading to use of additional rhythm control in
      clinical practice have not been thoroughly defined. METHODS: The ORBIT-AF
      registry enrolled patients with AF from a broad range of practice settings and
      collected data on rate versus rhythm control, as indicated by the treating
      physician. Multivariable logistic regression analysis was performed to identify
      factors associated with each strategy. RESULTS: Of 10,061 patients enrolled,
      6,859 (68%) were managed with rate only control versus 3,202 (32%) with rhythm
      control. Patients managed with rate control were significantly older and more
      likely to have hypertension, heart failure, prior stroke, and gastrointestinal
      bleeds. They also had fewer AF-related symptoms (41% with no symptoms vs 31% for
      rhythm control). Systemic anticoagulation was prescribed for 5,448 (79%) rate
      control patients versus 2,219 (69%) rhythm-control patients (P < .0001). After
      multivariable adjustment, patients with higher symptom scores (severe symptoms
      vs. none, OR 1.62, 95% CI 1.41-1.87) and those referred to electrophysiologists
      (OR 1.64, 95% CI 1.45-1.85) were more likely to be managed with a rhythm control
      strategy. CONCLUSIONS: In this outpatient registry of US clinical practice, the
      majority of patients with AF were managed with rate control alone. Patients with
      more symptoms and who were treated by an electrophysiologist were more likely to
      receive rhythm-control therapies. A significant proportion of AF patients,
      regardless of treatment strategy, were not treated with anticoagulation for
      thromboembolism prophylaxis.

PMID- 23537982
TI  - Clinical outcomes and cost implications of routine early PCI after fibrinolysis:
      one-year follow-up of the Trial of Routine Angioplasty and Stenting after
      Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)
      study.
AB  - BACKGROUND: In patients with ST-elevation myocardial infarction treated with
      fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves
      clinical outcomes at 30 days compared with a more standard approach of performing
      early PCI only for failed fibrinolysis (s-PCI). METHODS: We report prespecified
      secondary clinical outcomes and cost implications of r-PCI compared with s-PCI
      from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was
      calculated based on a microcosting approach. Bootstrap method (5,000 samples) was
      used to calculate standard errors and 95% CI. RESULTS: At 1 year, rates of death
      or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%,
      P = .64) and subsequent revascularization after index hospitalization (6.9% vs
      8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in
      cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to
      $2,211). Since a greater proportion of patients were transported by air (vs land)
      in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was
      higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional
      post hoc cost scenario analyses. In a scenario where patients are transported by
      land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the
      difference in cost per patient between r-PCI and s-PCI was estimated to be CAD
      $108 (95% CI, -$1,114 to $1,344). CONCLUSIONS: At 1 year, there is no difference
      in the clinical composite outcome of death or reinfarction between r-PCI and s
      PCI strategies. Greater cost with r-PCI, although statistically insignificant, is
      economically important.

PMID- 23537983
TI  - Global cardiovascular clinical trials and geographic altitude.

PMID- 23537984
TI  - Response to "Global cardiovascular clinical trials and geographic altitude".

PMID- 23537985
TI  - The prognostic implication of high-sensitivity C-reactive protein in patients
      with established cardiomyopathy.

PMID- 23537986
TI  - Response to "The prognostic implication of high-sensitivity C-reactive protein in
      patients with established cardiomyopathy".

PMID- 23537987
TI  - Apolipoprotein E gene polymorphisms in Lebanese with hypercholesterolemia.
AB  - Apolipoprotein E (ApoE) has an important role in the metabolism of lipids through
      its major isoforms (epsilon2, epsilon3, epsilon4). In particular, ApoE epsilon4,
      has been considered as a major genetic risk factor for cardiovascular diseases
      (CVD). The aim of our study is to investigate the frequency of ApoE gene
      polymorphisms (rs 429358C>T, rs 7412C>T) and their relationship to lipid
      parameters in a group of Lebanese hypercholesterolemic subjects (22 males and 24
      females, aged 25-80 years). Lipid profile, apolipoproteins A-I and B were
      determined using fasting serum samples; and molecular analysis of ApoE
      polymorphisms using blood in EDTA tubes. The distribution of the four ApoE
      genotypes detected in this study was: epsilon3/epsilon3 (73.9%),
      epsilon3/epsilon4 (17.4%), epsilon2/epsilon3 (6.5%), and epsilon2/epsilon4 (2.2%)
      resulting in allelic frequencies for epsilon2, epsilon3 and epsilon4 of 4.3%,
      85.9% and 9.8%, respectively. No association was determined among any of the
      lipid parameters, gender and ApoE genotypes. Lipid parameters were not
      statistically different among various ApoE genotypes (p>0.05). ApoE epsilon2
      frequency was found to be lower than that previously reported for healthy
      Lebanese (7.2%). CVD is one of the major leading causes of mortality in Lebanon
      with a reported prevalence of 12.2% in males and 7.7% in females, which
      incidentally agrees with our finding regarding epsilon4 allelic frequency of
      13.6% in males and 6.3% in females. Consequently, larger prospective studies are
      recommended to highlight the correlation of ApoE polymorphisms to other
      biochemical and environmental factors involved in CVD.

PMID- 23537988
TI  - Study of FMR1 gene association with ovarian dysfunction in a sample from the
      Basque Country.
AB  - Premature ovarian failure (POF) is defined as cessation of menses before the age
      of 40. The most significant single gene associated with POF is the Fragile X
      Mental Retardation 1 gene (FMR1). In the present work we screened women with
      fertility problems from the Basque Country in order to determine, whether in
      these women, FMR1 CGG repeat size in the intermediate and premutation range was
      associated with their pathology, and whether intermediate and premutation
      carriers had endocrine signs of diminished ovarian function, using the most
      established measure of ovarian reserve, the gonadotropin FSH. A patient sample of
      41 women with ovarian insufficiency and a control sample of 32 women with no
      fertility problems from the Basque Country were examined. The patient sample was
      classified into three categories according to the results of the retrospective
      assessment of their ovarian function. In group 2 of patients, women with
      irregular cycles, reduced fecundity and FSH levels >= 10IU/l, there is a
      significant increase in the number of intermediate and premutation FMR1 alleles
      (35-54 CGG repeats). In group 3 of patients, women with amenorrhea for at least
      four consecutive months and FSH levels >= 10IU/l, a significant increase in the
      number of intermediate FMR1 alleles (35-54 CGG repeats) was found in patients
      compared with controls. In this group all the patients had a serum concentration
      > 40 IU/l. The results suggest that in the analysed Basque sample the FMR1 gene
      has a role in the aetiology of POF. However, elevated FSH levels are more related
      to the menstrual cycle pattern than to the CGG repeat size.

PMID- 23537989
TI  - Case scenario and inquiry in response to: diagnostic utility of HFE variants in
      Spanish patients. Gene 2013; 514 (1): 31-35.

PMID- 23537990
TI  - Comparing methods for metabolic network analysis and an application to metabolic
      engineering.
AB  - Bioinformatics tools have facilitated the reconstruction and analysis of cellular
      metabolism of various organisms based on information encoded in their genomes.
      Characterization of cellular metabolism is useful to understand the phenotypic
      capabilities of these organisms. It has been done quantitatively through the
      analysis of pathway operations. There are several in silico approaches for
      analyzing metabolic networks, including structural and stoichiometric analysis,
      metabolic flux analysis, metabolic control analysis, and several kinetic modeling
      based analyses. They can serve as a virtual laboratory to give insights into
      basic principles of cellular functions. This article summarizes the progress and
      advances in software and algorithm development for metabolic network analysis,
      along with their applications relevant to cellular physiology, and metabolic
      engineering with an emphasis on microbial strain optimization. Moreover, it
      provides a detailed comparative analysis of existing approaches under different
      categories.

PMID- 23537991
TI  - Association between the polymorphisms of glutathione S-transferase genes and
      rheumatoid arthritis: a meta-analysis.
AB  - The glutathione S-transferases (GSTs) are a family of phase II xenobiotic
      metabolizing enzymes known to be involved in the detoxification and elimination
      of reactive oxygen species (ROS), thus defending tissues against oxidative
      stress. Recently, several studies have examined the potential contributions of
      GSTM1 and GSTT1 gene polymorphisms toward susceptibility to rheumatoid arthritis
      (RA), but these studies have produced diverse results. To verify the association
      between GSTM1 and GSTT1 gene polymorphisms and susceptibility to RA, we conducted
      a meta-analysis of all relevant reports cited in MEDLINE/PubMed before April
      2012. A meta-analysis on the association between the GSTM1 polymorphism and RA
      was performed for 4636 patients with RA and 3916 controls from 8 published
      studies. In addition, a total of 5 studies involving 3174 RA patients and 2958
      controls were considered in the meta-analysis of the association between the
      GSTT1 polymorphism and RA. No significant association was found between the GSTM1
      null genotype and RA susceptibility in all subjects; however, a significant
      increased risk was found in East Asians. The GSTT1 null genotype was not
      associated with susceptibility to RA in any study subject. No apparent effect of
      smoking was found in stratified analysis. The results of our meta-analysis
      indicated that the GSTM1 null genotype is significantly associated with RA in
      East Asians alone, indicating that GSTM1 is another non-human leukocyte antigen
      (non-HLA) susceptibility gene for RA in East Asian populations.

PMID- 23537992
TI  - Complement component C6 deficiency in a Spanish family: implications for clinical
      and molecular diagnosis.
AB  - Complement component C6 deficiency is a genetic disease presenting as increased
      susceptibility to invasive Neisseria meningitidis infections. This disorder has
      rarely been diagnosed in the Spanish population. In this work we report the
      immunochemical and molecular characterization of complement C6 deficiency in a
      Spanish patient showing no detectable functional activity of either the classical
      or alternative complement pathways and reporting a history of several episodes of
      meningococcal meningitis. The levels of individual complement components C3, C4,
      C5, C7, C8 and C9 were within the normal range. However, C6 level was low in the
      patient's serum as measured by radial immunodiffusion. Exon-specific polymerase
      chain reaction and sequencing of the C6 gene revealed a previously described
      homozygous single base deletion in exon 6 (c.821delA), leading to a shift in the
      reading frame that caused the generation of a downstream stop codon, which, in
      turn, provoked the truncation of the C6 protein (p.Gln274fs). To our knowledge,
      this is the first report on the c.821delA mutation in the Spanish population,
      which has previously only been identified in individuals of African ancestry.
      Characterization of this mutation was thought interesting in order to elucidate
      its source and help understand the molecular basis of this uncommon deficiency in
      our population. Moreover, this report highlights the importance of complement
      screening in cases of repeated meningococcal infections in order to establish its
      involvement and to consider adequate clinical recommendations such as
      prophylactic antibiotics or meningococcal vaccines and, subsequently, for genetic
      counselling.

PMID- 23537993
TI  - Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk.
AB  - ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway,
      which is involved in the removal of a wide variety of DNA lesions. To determine
      whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric
      cancer, we conducted a hospital-based case-control study of 350 cases and 468
      cancer-free controls. In the logistic regression (LR) analysis, we found a
      significantly decreased risk of gastric cancer associated with the rs744154 GC/CC
      genotypes [adjusted odds ratio (OR)=0.56, 95% confidence interval (CI)=0.42-0.75,
      false discovery rate (FDR) P=0.003] compared with the wild-type GG genotype.
      Haplotype-based association study revealed that the CGC haplotype that containing
      the rs744154 C allele can decrease the risk of gastric cancer compared with the
      most common haplotype GGT (adjusted OR=0.61, 95% CI=0.46-0.81). Using the
      multifactor dimensionality reduction (MDR) analysis, we identified that the SNP
      rs744154 and smoking status were the best two predictive factors for gastric
      cancer with a testing accuracy of 55.76% and a perfect cross-validation
      consistency (CVC) of 10 (P=0.001). Furthermore, the smokers with the rs744154
      GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR=0.55, 95%
      CI=0.35-0.85) compared with the smokers with the GG genotype using multivariate
      LR analysis. The above findings consistently suggested that genetic variants in
      the ERCC4 gene may play a protective role in the etiology of gastric cancer, even
      in the smokers.

PMID- 23537994
TI  - Subtractive phage display technology identifies zebrafish marcksb that is
      required for gastrulation.
AB  - In the present study, we used a phage display technique to screen differentially
      expressed proteins from zebrafish post-gastrula embryos. With a subtractive
      screening approach, 6 types of single-chain Fv fragments (scFvs) were screened
      out from an scFv antibody phage display library by biopanning against zebrafish
      embryonic homogenate. Four scFv fragments (scFv1, scFv3, scFv4 and scFv6) showed
      significantly stronger binding to the tailbud embryos than to the 30%-epiboly
      embryos. A T7 phage display cDNA library was constructed from zebrafish tailbud
      embryos and used to identify the antigens potentially recognized by scFv1, which
      showed the highest frequency and strongest binding against the tailbud embryos.
      We acquired 4 candidate epitopes using scFv1 and the corresponding genes showed
      significantly higher expression levels at tailbud stage than at 30%-epiboly. The
      most potent epitope of scFv1 was the clone scFv1-2, which showed strong homology
      to zebrafish myristoylated alanine-rich C-kinase substrate b (Marcksb). Western
      blot analysis confirmed the high expression of marcksb in the post-gastrula
      embryos, and the endogenous expression of Marcksb was interfered by injection of
      scFv1. Zebrafish marcksb showed dynamic expression patterns during embryonic
      development. Knockdown of marcksb strongly affected gastrulation movements.
      Moreover, we revealed that zebrafish marcksb is required for cell membrane
      protrusion and F-actin alignment. Thus, our study uncovered 4 types of scFvs
      binding to zebrafish post-gastrula embryos, and the epitope of scFv1 was found to
      be required for normal gastrulation of zebrafish. To our knowledge, this was the
      first attempt to combine phage display technique with the embryonic and
      developmental study of vertebrates, and we were able to identify zebrafish
      marcksb that was required for gastrulation.

PMID- 23537995
TI  - Evidence of colorectal cancer risk associated variant Lys25Ser in the proximity
      of human bone morphogenetic protein 2.
AB  - Colorectal cancer (CRC) is the third most prevalent cancer and fourth leading
      cause of cancer-related deaths globally. It has been shown that the nsSNP
      variants play an important role in diseases, however it remained unclear how
      these variants are associated with the disease. Recently, several CRC risk
      associated SNPs have been discovered, however rs961253 (Lys25Arg at 20p12.3)
      located in the proximity of bone morphogenetic protein 2 (Bmp2) and fermitin
      family homolog 1 Fermt1 genes have been reported to be highly associated with the
      CRC risk. Here we provide evidence for the first time in silico biological
      functional and structural implications of non-synonymous (nsSNPs) CRC disease
      associated variant Lys25Arg via molecular dynamic (MD) simulation. Protein
      structural analysis was performed with a particular variant allele (A/C,
      Lys25Arg) and compared with the predicted native protein structure. Our results
      showed that this nsSNP will cause changes in the protein structure and as a
      result is associated with the disease. In addition to the native and mutant 3D
      structures of CRC associated risk allele protein domain (CRAPD), they were also
      analyzed using solvent accessibility models for further protein stability
      confirmation. Taken together, this study confirmed that this variant has
      functional effect and structural impact on the CRAPD and may play an important
      role in CRC disease progression; hence it could be a reasonable approach for
      studying the effect of other deleterious variants in future studies.

PMID- 23537996
TI  - MiR-27a suppresses triglyceride accumulation and affects gene mRNA expression
      associated with fat metabolism in dairy goat mammary gland epithelial cells.
AB  - MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22
      nucleotides, participate in various biological metabolic processes. miR-27a is a
      miRNA that is known to regulate fat synthesis and differentiation in preadipocyte
      cells. However, little is known regarding the role that miR-27a plays in
      regulating goat milk fat synthesis. In this study, we determined the miR-27a
      expression profile in goat mammary gland and found that miR-27a expression was
      correlated with the lactation cycle. Additionally, prolactin promoted miR-27a
      expression in goat mammary gland epithelial cells. Further functional analysis
      showed that over-expression of miR-27a down-regulated triglyceride accumulation
      and decreased the ratio of unsaturated/saturated fatty acid in mammary gland
      epithelial cells. miR-27a also significantly affected mRNA expression related to
      milk fat metabolism. Specifically, over-expression of miR-27a reduced gene mRNA
      expression associated with triglyceride synthesis by suppressing PPARgamma
      protein levels. This study provides the first experimental evidence that miR-27a
      regulates triglyceride synthesis in goat mammary gland epithelial cells and
      improves our understanding about the importance of miRNAs in milk fat synthesis.

PMID- 23537997
TI  - SNV and haplotype analysis reveals new CSRP1 variants associated with growth and
      carcass traits.
AB  - The cysteine and glycine-rich protein 1 and 2 genes (CSRP1 and CSRP2) are an
      effective growth factor in promoting skeletal muscle growth in vitro and vivo.
      However, in cattle, the information on the CSRP1 and CSRP2 genes is very limited.
      The aim of this study was to examine the association of the CSRP1 and CSRP2
      variants with growth and carcass traits in cattle breeds. Three single nucleotide
      variants (SNVs) were identified within the bovine CSRP1 gene, whereas CSRP2 gene
      has not detected any SNVs, using DNA pooled sequencing, PCR-RFLP, and forced PCR
      RFLP methods. These SNVs include g. 801T>C (Intron 2), g. 46T>C (Exon 3) and g.
      99C>G (Intron 3). Besides, we also investigated haplotype frequencies and linkage
      disequilibrium (LD) coefficients for three SNVs in all study populations. LD and
      haplotype structure of CSRP1 were different between breeds. The result of
      haplotype analysis demonstrated eight haplotype present in QC (Qinchuan) and one
      haplotype in CH (Chinese Holstein). Only haplotype 1 (TTC), shared by all two
      populations, comprised 10.74% and 100.00%, of all haplotypes observed in QC and
      CH, respectively. Haplotype 5 (CTC) had the highest haplotype frequencies in QC
      (30.98%) and haplotype 1 had the highest haplotype frequencies in CH (100.00%).
      The statistical analyses indicated that one single SNV and 19 combined haplotypes
      were significantly or highly significantly associated with growth and carcass
      traits in the QC cattle population (P<0.05 or P<0.01). Quantitative real-time PCR
      (qRT-PCR) analyses showed that the bovine CSRP1 and CSRP2 genes were widely
      expressed in many tissues. The results of this study suggest that the CSRP1 gene
      possibly is a strong candidate gene that affects growth and carcass traits in the
      Chinese beef cattle breeding.

PMID- 23537998
TI  - Osteoid osteoma of the acetabular fossa: five cases treated with percutaneous
      resection.
AB  - BACKGROUND: Osteoid osteoma is a painful benign osteogenic tumour for which the
      treatment objective is surgical resection of the nidus. The acetabular fossa is
      an uncommon site of involvement where surgical access can prove challenging.
      MATERIALS AND METHODS: We report a case-series composed of five patients with
      osteoid osteoma of the acetabular fossa treated with percutaneous bone resection
      and drilling under computed tomography guidance. RESULTS: All five patients had
      an uneventful postoperative course with immediate pain relief that was sustained
      over time. DISCUSSION: The outcomes achieved using our percutaneous technique
      compare favourably with those of other percutaneous methods, most notably
      regarding pain relief and patient tolerance of the procedure. CONCLUSION:
      Percutaneous bone resection and drilling under computed tomography guidance
      proved effective for the treatment of osteoid osteoma involving the acetabular
      fossa. LEVEL OF EVIDENCE: Level IV.

PMID- 23537999
TI  - A novel application of direct force control to perform in-vitro biomechanical
      tests using robotic technology.
AB  - This paper presents a novel application of direct force control to test
      biological specimens using a serial manipulator with 6 degrees of freedom Direct
      force control compares actual force/moment values with desired values of load.
      The error is compensated by a proportional/integral controller (PI), a damping
      factor implemented with the velocity of the robot and acting in the direction of
      the force and a feedforward compensation. The controller works with a frequency
      of 0.5 kHz which enhances its performance due to the direct force feedback loop.
      A fresh porcine cervical spine C2-C4 was used. All muscle tissues were removed
      while leaving intact all ligaments and bony tissue. The specimen was loaded
      separately with +/-3 Nm in every spatial axis. The mean errors in the
      unconstrained axes in the present study were less than 1.70 N and 0.32 Nm. Direct
      force control of 6 axes with a high controller frequency of 0.5 kHz developed in
      this methodology shows a successful procedure to perform biomechanical in-vitro
      tests. The controller demonstrated the ability to maintain zero load targets in
      the unconstrained axes. This control approach allows the application of pure
      moments in order to perform in vitro biomechanical experiments with spine
      segments.

PMID- 23538000
TI  - Impact differences in ground reaction force and center of mass between the first
      and second landing phases of a drop vertical jump and their implications for
      injury risk assessment.
AB  - The drop vertical jump (DVJ) task is commonly used to assess biomechanical
      performance measures that are associated with ACL injury risk in athletes.
      Previous investigations have solely assessed the first landing phase. We examined
      the first and second landings of a DVJ for differences in the magnitude of
      vertical ground reaction force (vGRF) and position of center of mass (CoM). A
      cohort of 239 adolescent female basketball athletes completed a series of DVJ
      tasks from an initial box height of 31 cm. Dual force platforms and a three
      dimensional motion capture system recorded force and positional data for each
      trial. There was no difference in peak vGRF between landings (p=0.445), but side
      to-side differences increased from the first to second landing (p=0.007).
      Participants demonstrated a lower minimum CoM during stance in the first landing
      than the second landing (p<0.001). The results have important implications for
      the future assessment of ACL injury risk behaviors in adolescent female athletes.
      Greater side-to-side asymmetry in vGRF and higher CoM during impact indicate the
      second landing of a DVJ may exhibit greater perturbation and better represent in
      game mechanics associated with ACL injury risk.

PMID- 23538002
TI  - Prediction of compressive stiffness of articular cartilage using Fourier
      transform infrared spectroscopy.
AB  - Unique biomechanical behavior of articular cartilage is a result of its structure
      and composition. Interrelationships of tissue constituents (collagen,
      proteoglycans (PGs) and water) and tissue biomechanical parameters have been
      studied, but it is evident that no constituent alone explains the tissue
      mechanics. Fourier transform infrared (FT-IR) spectra can provide detailed
      information about the biochemical composition of articular cartilage. In this
      study, a chemometric approach to predict the biomechanical behavior of articular
      cartilage directly from the FT-IR spectra, i.e., without converting the data into
      collagen and PG information, was investigated. Partial least squares regression
      (PLSR) was used to predict equilibrium modulus (n=32) and dynamic modulus (n=24)
      of bovine cartilage samples from their average FT-IR spectra. The linear
      correlation coefficients between the reference and predicted values of Young's
      modulus and dynamic modulus were r=0.866 (p<0.001) and r=0.898 (p<0.001),
      respectively. When the compressive biomechanical behavior of AC is predicted, the
      present study indicates that similar or improved results can be obtained with FT
      IR spectroscopy as compared to those of traditional biochemical methods.

PMID- 23538001
TI  - Does ankle joint power reflect type of muscle action of soleus and gastrocnemius
      during walking in cats and humans?
AB  - The main objective of this paper is to highlight the difficulties of identifying
      shortening and lengthening contractions based on analysis of power produced by
      resultant joint moments. For that purpose, we present net ankle joint powers and
      muscle fascicle/muscle-tendon unit (MTU) velocities for medial gastrocnemius (MG)
      and soleus (SO) muscles during walking in species of different size (humans and
      cats). For the cat, patterns of ankle joint power and MTU velocity of MG and SO
      during stance were similar: negative power (ankle moment*angular velocity<0),
      indicating absorption of mechanical energy, was associated with MTU lengthening,
      and positive power (generation of mechanical energy) was found during MTU
      shortening. This was also found for the general fascicle velocity pattern in SO.
      In contrast, substantial differences between ankle joint power and fascicle
      velocity patterns were observed for MG muscle. In humans, like cats, the patterns
      of ankle joint power and MTU velocity of SO and MG were similar. Unlike the cat,
      there were substantial differences between patterns of fascicle velocity and
      ankle joint power during stance in both muscles. These results indicate that
      during walking, only a small fraction of mechanical work of the ankle moment is
      either generated or absorbed by the muscle fascicles, thus confirming the
      contribution of in-series elastic structures and/or energy transfer via two-joint
      muscles. We conclude that ankle joint negative power does not necessarily
      indicate eccentric action of muscle fibers and that positive power cannot be
      exclusively attributed to muscle concentric action, especially in humans.

PMID- 23538003
TI  - Heterogeneity of bone mineral density and fatigue failure of human vertebrae.
AB  - There is increasing interest in using the heterogeneity of tissue properties in a
      bone for predicting its fracture risk. Heterogeneity of volumetric bone mineral
      density (BMD) as measured from quantitative computed tomography (QCT) is of
      particular interest as these measurements are clinically feasible. Previous
      examinations of the relationship between the BMD heterogeneity and the mechanical
      behavior of human vertebrae only considered quasistatic strength and were with
      limited number of samples. McCubbrey et al. (1995) studied the value of regional
      BMDs for predicting vertebral fatigue life, determined from short-cycle tests at
      force levels scaled with the estimated strength of the vertebra, but the focus of
      that work was in best predictor subsets without a specific focus on the
      heterogeneity of BMD or the positive vs negative direction of the relationships.
      The previous analysis also did not take into account the censored nature of the
      fatigue life data. As such, whether BMD heterogeneity is positively or negatively
      associated with fatigue life and whether this is independent of the average or
      minimum BMD are not clear. In the present work, we revisited the McCubbrey data
      for a preliminary examination of the relationship between BMD heterogeneity and
      fatigue life using survival analysis. The analysis suggests that BMD
      heterogeneity measured as the intra-vertebral standard deviation of BMDs in a
      vertebra is negatively associated with short cycle (high-amplitude) fatigue life
      independent of the average BMD. The results motivate further studies on the role
      of BMD heterogeneity in fatigue failure and clinical fracture risk of human
      vertebrae.

PMID- 23538004
TI  - Faecal levels of Bifidobacterium and Clostridium coccoides but not plasma
      lipopolysaccharide are inversely related to insulin and HOMA index in women.
AB  - BACKGROUND & AIMS: The abundance of specific microbes might be associated with
      plasma lipopolysaccharide and insulin levels. The aims were to quantify the
      abundance of specific microbes and plasma LPS in females and assess their
      association with anthropometric, body composition and biochemical measurements.
      METHODS: Seventeen lean (BMI 19-24.99 kg/m(2)) and fifteen obese females (BMI >
      30 kg/m(2)) participated. Anthropometry, body composition, food intake and
      biochemical analyses were assessed. Bacterial groups in faeces were analysed by
      qPCR method. RESULTS: Lactobacillus plantarum prevalence was higher (p = 0.005)
      and its counts tended to be higher in lean vs. obese group (p = 0.06).
      Bifidobacterium genus, Bifidobacterium longum, Clostridium coccoides and
      Clostridium leptum counts were higher in lean women (p < 0.05); prevalence and
      counts of Akkermansia muciniphila tended to be higher in lean group (p = 0.09, p
      = 0.06, respectively). Plasma LPS levels were similar between the study groups (p
      > 0.05). No association was found between LPS and bacterial levels or insulin.
      Bifidobacteria and C. coccoides counts were inversely associated with insulin and
      HOMA index. CONCLUSIONS: Abundance of specific microbes is distinct between obese
      and lean women, but is not associated with LPS level. Bifidobacterial and C.
      coccoides levels are associated with insulin sensitivity. These bacterial groups
      may be capable of modulating insulin action.

PMID- 23538005
TI  - Psychometric properties of the Brazilian version of the Tilburg frailty indicator
      (TFI).
AB  - This study aims to assess the psychometric properties of the Brazilian version of
      the TFI, an instrument that identifies frailty in elderly individuals. We
      interviewed 219 individuals aged 60 or older, living in the community.
      Individuals were predominantly female (52.5%) and mean age was 70.5 (+/-7.9)
      years. In order to assess test-retest reliability, 101 individuals were re
      interviewed by the same observer within seven to ten days after the first
      interview. The internal consistency of the instrument was assessed using
      Cronbach's alpha. To assess construct validity, we used established alternative
      measures for the items that constitute the TFI, such as: body mass index (BMI),
      timed up and go (TUG) test, whisper test, Snellen test, upper extremity strength
      clinical test and mini-mental state examination (MMSE). The test-retest
      reliability showed high percent agreement for all the items of the instrument,
      with values ranging from 63% to 100%. Test-retest reliabilities were good (total
      TFI score r=0.88; physical domain r=0.88; psychological domain r=0.88; and social
      domain r=0.67). Internal consistency reliability of the Brazilian version was
      satisfactory (Cronbach's alpha=0.78). The correlations between TFI items and
      their corresponding measures were consistent except for one item (related to
      "ability to deal with problems"), demonstrating both convergent and divergent
      construct validity of the TFI and its items. After the completion of all stages
      of transcultural adaptation, the Brazilian version of the TFI proved to be well
      suited for assessing frailty in the elderly population of Brazil.

PMID- 23538006
TI  - Transglutaminase type 2 in human abdominal aortic aneurysm is a potential factor
      in the stabilization of extracellular matrix.
AB  - OBJECTIVE: The aim of this study was to evaluate transglutaminase type 2 (TG2)
      expression in human abdominal aortic aneurysm (AAA) tissue and to elucidate a
      potential role of TG2 in AAA formation. TG2, which is a Ca(2+)-dependent cross
      linking enzyme, has been proven important for stabilizing the extracellular
      matrix. However, there is no evidence of the effect of TG2 on AAA formation in a
      human model. METHODS: Aortic wall tissues were obtained during surgery in AAA
      patients (n = 38) and in patients with aortoiliac occlusive disease (Control; n =
      4) in the Asan Medical Center from March 2011 to February 2012. In each AAA
      patient, the aortic neck (Neck) and maximally dilated portion (Max) of the
      aneurysm were sampled for analysis. TG2 expression was evaluated using
      immunohistochemistry and Western blotting. In addition, ex vivo experiments of
      isolated AAA tissue culture with the TG2 inhibitor cystamine and recombinant
      human TG2 were performed. RESULTS: Among 38 AAA patients, 11 had ruptured
      (contained or free) AAAs. The mean maximal diameter of AAAs was 6.09 +/- 1.46 cm.
      TG2 expressions of Max were significantly increased compared with those of
      Control (1.7-fold increase of Control; P = .00). Compared with Control, the
      intensities of tissue necrosis factor-alpha, matrix metalloproteinase (MMP)-2,
      MMP-9, and tissue inhibitors of metalloproteinase-2 were significantly
      upregulated in Max (1.7-fold, 1.5-fold, 1.3-fold, and 1.6-fold increases of
      Control; P = .00, P = .004, P = .046, and P = .007, respectively). Furthermore,
      double immunofluorescent staining showed that colocalization of TG2/transforming
      growth factor-beta or TG2/fibronectin was prominent in Max compared with those of
      Neck or Control. In addition, MMP-2 intensity was upregulated in ruptured AAAs
      compared with unruptured AAAs, with marginal significance (P = .078). Ex vivo
      experiments showed that protein expressions of tissue necrosis factor-alpha, MMP
      2, and MMP-9 in cultured AAA tissue were decreased by recombinant human TG2 but
      were increased by exogenous cystamine. CONCLUSIONS: The TG2 expression in the
      maximally dilated portion of AAAs was enhanced compared with that of nondilated
      aorta. It is suggested that TG2 has a potential effect in stabilization of
      extracellular matrix by inhibition of proinflammatory cytokines and MMPs or by
      interaction with fibronectin and transforming growth factor-beta.

PMID- 23538007
TI  - Epigallocatechin-3-gallate is a potent phytochemical inhibitor of intimal
      hyperplasia in the wire-injured carotid artery.
AB  - OBJECTIVE: Epigallocatechin-3-gallate (EGCG), a catechin gallate ester, is the
      major component of green tea and has been demonstrated to inhibit tumor growth as
      well as inhibit smooth muscle cell migration. We evaluated the effect of the
      phytochemicals resveratrol, allicin, sulforaphane (SFN), and EGCG on intimal
      hyperplasia in the carotid artery injury model. METHODS: Intimal hyperplasia was
      induced in carotid arteries of adult Sprague-Dawley rats with a wire injury.
      Experimental animals received intraperitoneal injections of one of the four
      phytochemicals daily beginning 1 day prior to surgery and continued for up to 4
      weeks. Control animals were administered saline. Carotid specimens were harvested
      at 2 weeks and subjected to quantitative image analysis. In addition, EGCG
      specimens were analyzed for cell proliferation, immunohistochemistry, and Western
      blot analysis. RESULTS: Quantitative image analysis showed significant
      phytochemical suppression of intimal hyperplasia at 2 and 4 weeks postoperatively
      with EGCG (62% decrease in intimal area). Significant decreases were also noted
      at 2 weeks for SFN (56%) and resveratrol (44%), whereas the decrease with allicin
      (24%) was not significant. Quantification of intimal hyperplasia by intima:media
      ratio showed similar results. Cell proliferation assay of specimens demonstrated
      suppression by EGCG. Immunohistochemical staining of EGCG-treated specimens
      showed extracellular signal-regulated kinase (ERK) suppression but not of the c
      jun N-terminal kinase or p38 pathways. Western blot analysis confirmed reduced
      ERK activation in arteries treated with EGCG. CONCLUSIONS: Intraperitoneal
      injection of the phytochemicals EGCG, SFN, resveratrol, and allicin have
      suppressive effects on the development of intimal hyperplasia in the carotid
      artery injury model, with maximal effect due to EGCG. The mechanism of EGCG
      action may be due to inhibition of ERK activation. EGCG may affect a common
      pathway underlying either neoplastic cellular growth or vascular smooth muscle
      cellular proliferation.

PMID- 23538008
TI  - Vasodilator and endovascular therapy for isolated superior mesenteric artery
      dissection.
AB  - OBJECTIVE: We report our experience in the treatment of isolated superior
      mesenteric artery dissection and review the clinical and imaging features
      reported in the literature. METHODS: A retrospective study was conducted of 18
      consecutive patients with isolated superior mesenteric artery dissection who
      presented at the Peking University Third Hospital between September 2008 and May
      2012. Their clinical characteristics, including age, sex, medical history, risk
      factors, symptoms, diagnostic imaging modality, and treatment, were analyzed.
      Also reviewed were 278 patients with isolated superior mesenteric artery
      dissection reported in the English language literature. The epidemiology,
      mechanism, clinical presentation, imaging features, and treatment were discussed.
      RESULTS: There were 14 men and four women with a mean age of 55.6 years (range,
      41-84 years). Four patients were asymptomatic, and 14 presented with acute-onset
      abdominal pain. The diagnosis was established by contrast-enhanced computed
      tomography in 17 patients and ultrasound imaging in one patient. All dissections
      were located at the anterior wall and around the convex curvature of the superior
      mesenteric artery. The decision to intervene was based on symptoms. Three
      asymptomatic patients underwent successful conservative management, and one
      asymptomatic patient with an aneurysmal dilated false lumen underwent
      endovascular stent placement. For the 14 symptomatic patients, definitive
      treatment included catheter-directed infusion of a vasodilator in four and stent
      placement combined with catheter-directed infusion of a vasodilator in 10, of
      whom one patient underwent hybrid stent placement. No complications or deaths
      occurred. During the mean 14.9-month (range, 1-40 month) follow-up period, all
      patients were asymptomatic, and patency of the superior mesenteric artery was
      demonstrated by contrast-enhanced computed tomography scan. CONCLUSIONS:
      Conservative management can be applied to asymptomatic patients with isolated
      superior mesenteric artery dissection. For symptomatic patients, stent placement
      is the definitive treatment if there is no arterial rupture or intestinal
      necrosis. Self-expanding bare stents that completely cover the curvature of the
      superior mesenteric artery are recommended. Catheter-directed infusion of a
      vasodilator can be an effective accessional process after stent placement.

PMID- 23538009
TI  - Successfully treated HIV-infected patients have differential expression of NK
      cell receptors (NKp46 and NKp30) according to AIDS status at presentation.
AB  - Differences in innate immune responses may be associated with different
      capabilities of controlling HIV infection, not necessarily reflected by CD4(+) T
      cell counts alone. We investigated by cytofluorometry the expression of NK cell
      receptors and ligands in 19 treated HIV-infected patients with CD4(+)<220 ml(-1)
      at presentation (11 AIDS, 8 non-AIDS) and 10 healthy donors. Expression of NKp46
      and NKp30 was significantly higher in non-AIDS vs. AIDS patients. Overall, the
      level of NKp46 expression directly correlated with the degree of NK cell
      cytotoxicity. As compared to healthy donors, in both groups, there was a similar
      increase of CD69 and HLA-DR expression in NK cells that directly correlated with
      the presence of activation markers (HLA-DR) on CD4(+) and CD8(+) T cells. As
      compared to AIDS, in non-AIDS patients in vitro activated CD4(+) showed higher
      expression of MIC-A (NKG2D ligand), with significantly higher Nectin-2/DNAM-1 and
      MIC-A/NKG2D ratios. Thus, NK cell responses in AIDS and non-AIDS patients with
      similar CD4(+) counts significantly differ despite similar treatment. This
      suggests an involvement of innate mechanisms, in preventing AIDS-defining
      opportunistic infections in HIV infection and further suggests, that CD4(+)
      absolute counts alone, may be inadequate to explain differences in the clinical
      outcome.

PMID- 23538010
TI  - The state of the evidence base for psychodynamic psychotherapy for children and
      adolescents.
AB  - This article reviews outcomes of psychodynamic psychotherapy (PP) for children
      and adolescents reported in articles identified by a comprehensive review of the
      literature on treatment evaluations of psychological and medical interventions
      for mental disorders in pediatric populations. The review identified 48 reports
      based on 33 studies. While there is evidence of substantial clinical gains
      associated with PP, in almost all the studies, when contrasted with family-based
      interventions, PP fares no better and appears to produce outcomes with some delay
      relative to family-based therapies. Further rigorous evaluations are needed, but
      evidence to date suggests that the context in which PP is delivered should be
      extended from the traditional context of individual therapy and parents should be
      included in the treatment of children.

PMID- 23538011
TI  - Dyadic psychotherapy with infants and young children: child-parent psychotherapy.
AB  - This article briefly reviews the historical and empiric foundations of dyadic
      psychotherapy, highlighting the evolution of the central tenet that very young
      children exist in a relational context. The target of therapeutic intervention
      must therefore be the caregiver-child relationship. General features of dyadic
      psychotherapy are discussed, as well as aspects that are unique to the treatment
      of very young children. An overview of the goals and intervention modalities of
      Child-Parent Psychotherapy is provided as an example of an evidence-based dyadic
      intervention that incorporates theoretical principles and techniques of
      psychodynamic psychotherapy.

PMID- 23538012
TI  - Family intervention as a developmental psychodynamic therapy.
AB  - Families are the context for development. One key way families influence
      developing children is through family experience, which becomes part of the
      child's inner world. It is through this cognitive template that the child
      interprets the world and negotiates developmental challenges. This article
      reviews a continuum of family interventions targeting interactions that shape the
      child's mind, and offers guidance to the clinician about when to use individual
      and family approaches.

PMID- 23538013
TI  - Play technique in psychodynamic psychotherapy.
AB  - Imaginary play is often a child's best way of communicating affects, fantasies,
      and internal states. In play children are freer to express their forbidden and
      conflicted thoughts. Consequently, one of the best ways for the therapist to
      enter the child's world is to do so from within the displacement of the play
      process. For children who cannot play, the therapist's goal is to teach the child
      to use play as a means of communication and to create meaning. This article
      present clinical examples to illustrate how the author uses play in the clinical
      situation.

PMID- 23538014
TI  - Games children play: board games in psychodynamic psychotherapy.
AB  - Children of latency age have typically outgrown dramatic play but have not yet
      developed the ability to talk about their thoughts and feelings in therapy; at
      this stage they often play structured board games, during their own playtime and
      during therapy sessions. This article discusses ways to use board-game play
      therapeutically, by watching the way children stretch and bend the rules to
      display their psychological self-states, and by interpreting their experiences
      within the play.

PMID- 23538015
TI  - Mentalizing-based treatment with adolescents and families.
AB  - In this article, the process of mentalizing, its components, and role in self
      regulation and attachment are reviewed. An examination is presented of the
      neurodevelopmental changes affecting the adolescent's capacity to mentalize and
      the role of such compromised mentalizing in the adolescent's vulnerability to
      adaptive breakdown and psychopathology, in general, and to emerging personality
      disorders, in particular. The principles, objectives, and core features of
      mentalizing-based treatment and its application to adolescents and families are
      discussed.

PMID- 23538016
TI  - A new model of techniques for concurrent psychodynamic work with parents of child
      and adolescent psychotherapy patients.
AB  - To address the neglect of the importance of parent work in the psychodynamic
      psychotherapy of children and adolescents, the authors present a model of
      concurrent dynamic parent work that has demonstrated success with patients of all
      ages. The model includes dual goals for all therapies, addresses the challenge of
      confidentiality by differentiating privacy and secrecy, and emphasizes the
      importance of parent work throughout treatment.

PMID- 23538017
TI  - Psychodynamic perspectives on psychotropic medications for children and
      adolescents.
AB  - Recent trends in pediatric psychopharmacology have resulted in advances in
      treatment but also an overly optimistic and, at times, simplistic extension of
      pediatric psychopharmacology practice. Concerns about these changes in the field
      are discussed. The authors outline how understanding the meaning of medications
      to all those involved in the prescribing process can help integrate our thinking
      about this complex interaction with patients and their families.

PMID- 23538018
TI  - Child and Adolescent Psychiatric Clinics of North America. Psychodynamic
      treatment approaches to psychopathology, vol 2. Preface.

PMID- 23538019
TI  - Staged palliation of hypoplastic left heart syndrome: trends in mortality, cost,
      and length of stay using a national database from 2000 through 2009.
AB  - Staged surgical palliation has revolutionized the care of patients with
      hypoplastic left heart syndrome (HLHS), although the outcomes of survival and
      cost at a national level remain unclear. This study sought to evaluate (1) trends
      in HLHS surgical outcomes including in-hospital mortality, length of stay (LOS),
      and cost, and (2) patient and hospital risk factors associated with these
      outcomes. Hospitalizations for patients with HLHS, including stage I, II, and III
      palliations, were analyzed using the Kids' Inpatient Database from 2000 through
      2009. Trends in mortality, LOS, and cost were analyzed and chi-squared tests were
      used to test association between categorical variables. Patient and hospital
      characteristics associated with death were analyzed using logistic regression and
      associations with LOS were analyzed using ordinary least squared regression.
      There were 16,923 hospital admissions in patients with HLHS of which 5,672 (34%)
      included surgical intervention. Total (3,201-5,102) and surgery-specific
      admissions (1,165-1,618) increased from 2000 to 2009. Mortality decreased 14% per
      year in stage III palliations (odds ratio [OR] 0.86; 95% confidence interval
      [CI]: 0.79-0.94) and 6% per year for stage I palliations (OR 0.94; 95% CI 0.90
      0.99) but not for stage II palliations (OR 1.01; 95% CI; 0.89-1.14). Length of
      stay increased for stage I and II palliations; however, per-patient hospital cost
      decreased in 2009. In conclusion, recent decrease in per patient cost for staged
      surgical palliation for HLHS has correlated temporally with improved mortality.

PMID- 23538020
TI  - Impact of adding ezetimibe to statin to achieve low-density lipoprotein
      cholesterol goal (from the Clinical Outcomes Utilizing Revascularization and
      Aggressive Drug Evaluation [COURAGE] trial).
AB  - In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug
      Evaluation (COURAGE) study, a revascularization strategy trial with optimal
      medical therapy in both arms, the low-density lipoprotein (LDL) cholesterol goal
      was 60 to 85 mg/dl; this was revised to <70 mg/dl in 2004. COURAGE patients (n =
      2,287) were titrated with increasing statin doses to achieve the initial LDL
      cholesterol goal using a prespecified protocol. Ezetimibe was not available when
      study enrollment began in 1999 but became available after approval in 2003. After
      maximizing statin dose, ezetimibe was added to reach the LDL cholesterol goal in
      34% of patients (n = 734). Median baseline LDL cholesterol was higher in patients
      who received ezetimibe than in those who did not (109 vs 96 mg/dl). At baseline,
      18% of patients who would later receive ezetimibe had LDL cholesterol <85 mg/dl,
      and 8% had LDL cholesterol <70 mg/dl. On maximum tolerated statin (with or
      without other lipid-lowering drugs), 40% had LDL cholesterol <85 mg/dl and 23%
      had LDL cholesterol <70 mg/dl before starting ezetimibe. At the final study
      visit, 68% of ezetimibe patients achieved LDL cholesterol <85 mg/dl, and 46%
      achieved LDL cholesterol <70 mg/dl. Using Cox regression analysis, the most
      significant factors associated with achieving LDL cholesterol goals were lower
      baseline LDL cholesterol, average statin dose, and ezetimibe use. In conclusion,
      after maximizing statin dose, the addition of ezetimibe results in a substantial
      increase in the percentage of patients who reach LDL cholesterol goal, a key
      component of optimal medical therapy.

PMID- 23538021
TI  - Evaluation of circulation disorder in coronary slow flow by fundus fluorescein
      angiography.
AB  - Coronary slow flow (CSF) may be a reflection of a systemic slow-flow phenomenon
      in the coronary arterial tree. In this study, the CSF group consisted of 24 men
      (77.4%) and 7 women (22.5%). An age- and gender-matched normal coronary artery
      (control) group was composed of 21 men (72.4%) and 8 women (27.5%). Retinal
      arteriovenous circulation time was measured using fundus fluorescein angiography
      as a part of the microcirculation and the circulation time between the
      antecubital vein and the retina as a part of the systemic circulation in patients
      with CSF and controls with normal coronary arteries. The mean arm-retina
      circulation time was 19.0 +/- 5.7 seconds in the CSF group and 14.1 +/- 3.1
      seconds in the control group (p <0.001). The mean retinal arteriovenous passage
      time was 2.6 +/- 0.9 seconds in the CSF group and 2.1 +/- 0.7 seconds in the
      control group (p = 0.001). Strikingly, retinal findings of chronic central serous
      retinopathy were observed in 3 patients in the CSF group. In conclusion, CSF may
      indeed be a part of a systemic slow-flow phenomenon. The association of central
      serous retinopathy with this condition suggests that corticosteroids and the
      sympathetic system may play important roles in the pathogenesis of the disease by
      causing or contributing to increases in microvascular resistance and tonus.

PMID- 23538022
TI  - Correlation of platelet reactivity and C-reactive protein levels to occurrence of
      peri-procedural myocardial infarction in patients undergoing percutaneous
      coronary intervention (from the ARMYDA-CRP study).
AB  - The incremental predictive value of high inflammatory status and high on
      treatment platelet reactivity (HPR) on the occurrence of periprocedural
      myocardial infarction (PMI) after percutaneous coronary intervention (PCI) has
      not been characterized. The aim of this study was to evaluate the correlation of
      elevated C-reactive protein (CRP) level and/or HPR with the incidence of PMI in
      patients who undergo PCI. Five hundred consecutive patients treated with
      clopidogrel who underwent PCI had preprocedural measurement of CRP levels and
      platelet reactivity using the point-of-care VerifyNow P2Y12 assay. Elevated
      inflammatory status was defined as CRP >3 mg/L and HPR as P2Y12 reactivity units
      >=240. The primary end point was the incidence of PMI in relation to platelet
      reactivity and/or inflammatory status. Rates of PMI were increased in patients
      with CRP levels >3 mg/L (10.9% vs 4.6% in those with normal levels, odds ratio
      2.4, 95% confidence interval 1.2 to 4.5, p = 0.015) and in patients with HPR (11%
      vs 5.5% in those without HPR, odds ratio 2.2, 95% confidence interval 1.2-4.4, p
      = 0.018). The occurrence of PMI was highest in the subgroup with HPR and high
      inflammatory status (16.6% vs 3.6% in patients with CRP <=3 mg/L and P2Y12
      reactivity units <240, odds ratio 4.3, 95% confidence interval 1.5 to 12.6, p =
      0.008). HPR in association with elevated CRP levels resulted in a significant
      increase in the discriminatory power of a model including clinical and procedural
      variables in predicting PMI (area under the curve 0.811, p = 0.041). In
      conclusion, in patients who undergo PCI, baseline stratification according to
      platelet reactivity and inflammatory status may identify those at higher risk for
      PMI.

PMID- 23538023
TI  - Uranium and other natural radionuclides in the sediments of a Mediterranean fjord
      like embayment, Amvrakikos Gulf (Ionian Sea), Greece.
AB  - The distribution of the natural radionuclides ((238)U, (232)Th, (226)Ra, (40)K)
      and the artificial (137)Cs was studied in sediment cores collected from
      Amvrakikos Gulf, a seasonal anoxic marine basin, using gamma-ray spectrometry.
      The activity of radionuclides, along with the concentrations of Fe and Mn, were
      also studied in relation to the total organic carbon and the granulometric
      fractions of the sediments. The results obtained revealed higher (238)U activity
      concentrations in all the examined sediment samples compared to the world and
      Greek average values for soil. The high activity values of (238)U are attributed,
      besides the lattice-held fraction, to phosphate fertilizer inputs in the Gulf via
      major rivers and/or to alteration processes of phosphate ores located mainly in
      the drainage basin of the river Louros. The elevated activity values of (40)K
      could be attributed to the mineralogical composition of the sediments and to
      phosphate fertilizers containing potassium. Organic matter seems to be a more
      efficient sorbent for U than clay minerals and amorphous Fe and Mn-oxyhydroxides.
      Scanning electron microscopy, together with qualitative analysis of some
      smectites, reveals the occurrence of U, suggesting a limited absorption of U onto
      clay minerals. The applied BCR sequential extraction procedure revealed that U
      was found mainly in the refractory phase or associated with organic matter and to
      a lesser extent as surface-coating oxides, with the exception of one sediment
      core which is characterized by high content of fresh marine organic matter and
      presents high percentage of U in the exchangeable fraction.

PMID- 23538024
TI  - A history of the role of the hERG channel in cardiac risk assessment.
AB  - The human ether-a-go-go-related gene (hERG, Kv11.1) K(+) channel plays an
      important role in cardiac repolarization. Following its cloning and expression it
      was established that inhibition of this channel was the molecular mechanism for
      many non-antiarrhythmic drugs that produce torsades de pointes associated with QT
      prolongation. Therefore the study of in vitro drug-hERG interactions has become
      an important part of modern safety pharmacology. Manual and automated patch clamp
      electrophysiology, in silico modeling, and hERG trafficking assays have been
      developed to aid in this study. The correlation between in vitro hERG IC50, drug
      exposure, QT prolongation in the thorough QT clinical trial and risk of TdP has
      greatly reduced drug withdrawals due to TdP. However a significant association
      with Type 1 errors in particular remains and may have a negative impact on drug
      development. Combining hERG data with other non-clinical and clinical markers of
      proarrhythmia will increase the specificity and sensitivity of cardiac risk
      assessment. hERG will continue to play an important role in drug development and
      safety pharmacology in the future. 

PMID- 23538025
TI  - Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis
      by regulating antioxidant and inflammatory mediators.
AB  - Inflammatory bowel diseases (IBD), including Crohn's disease and Ulcerative
      colitis (UC), are life-long and recurrent disorders of the gastrointestinal tract
      with unknown etiology. The present study is designed to evaluate the ameliorative
      effect of Bauhinia tomentosa during ulcerative colitis (UC). Three groups of
      animals (n=6) were treated with B. tomentosa (5, 10, 20 mg/kg B.wt respectively)
      for 5 consecutive days before induction of UC. UC was induced by intracolonic
      injection of 3% acetic acid. The colonic mucosal injury was assessed by
      macroscopic scoring and histological examination. Furthermore, the mucosal
      content of lipid peroxidation (LPO), reduced glutathione (GSH), nitric oxide
      (NO), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity
      confirms that B. tomentosa could significantly inhibit colitis in a dose
      dependent manner. The myeloperoxidase (MPO), tumor necrosis factor (TNF-alpha),
      inducible nitric oxide synthase (iNOS) expression studies and lactate
      dehydrogenase (LDH) assay also supported that B. tomentosa could significantly
      inhibit experimental colitis. The effect was comparable to the standard drug
      sulfasalazine. Colonic mucosal injury parallels with the result of histological
      and biochemical evaluations. The extracts obtained from B. tomentosa possess
      active substances, which exert marked protective effects in acute experimental
      colitis, possibly by regulating the antioxidant and inflammatory mediators.

PMID- 23538026
TI  - Susceptibility to T cell-mediated liver injury is enhanced in asialoglycoprotein
      receptor-deficient mice.
AB  - T cell activation and associated pro-inflammatory cytokine production is a
      pathological feature of inflammatory liver disease. It is also known that liver
      injury is associated with marked impairments in the function of many hepatic
      proteins including a hepatocyte-specific binding protein, the asialoglycoprotein
      receptor (ASGPR). Recently, it has been suggested that hepatic ASGPRs may play an
      important role in the physiological regulation of T lymphocytes, leading to our
      hypothesis that ASGPR defects correlate with inflammatory-mediated events in
      liver diseases. Therefore, in this study we investigated whether changes in
      hepatocellular ASGPR expression were related to the dysregulation of intrahepatic
      T lymphocytes and correlate with the development of T-cell mediated hepatitis.
      Mice lacking functional ASGPRs (receptor-deficient, RD), and wild-type (WT)
      controls were intravenously injected with T-cell mitogens, Concanavalin A (Con A)
      or anti-CD3 antibody. As a result of T cell mitogen treatment, RD mice lacking
      hepatic ASGPRs displayed enhancements in liver pathology, transaminase
      activities, proinflammatory cytokine expression, and caspase activation compared
      to that observed in normal WT mice. Furthermore, FACS analysis demonstrated that
      T-cell mitogen administration resulted in a significant rise in the percentage of
      CD8+ lymphocytes present in the livers of RD animals versus WT mice. Since these
      two mouse strains differ only in whether they express the hepatic ASGPR, it can
      be concluded that proper ASGPR function exerts a protective effect against T cell
      mediated hepatitis and that impairments to this hepatic receptor could be related
      to the accumulation of cytotoxic T cells that are observed in inflammatory liver
      diseases.

PMID- 23538027
TI  - Ruscogenin attenuates monocrotaline-induced pulmonary hypertension in rats.
AB  - Inflammation, endothelial dysfunction, and thrombosis contribute to the
      pathogenesis and development of human pulmonary arterial hypertension (PAH). The
      aim of this study was to investigate the effects of ruscogenin, a natural anti
      inflammatory and anti-thrombotic agent, on the development of monocrotaline (MCT)
      induced PAH in rats. Our results revealed that ruscogenin had favorable effects
      on hemodynamics and pulmonary vascular remodeling, preventing the development of
      PAH 3 weeks after MCT. In addition, ruscogenin resulted in markedly reduced
      expression of inflammatory cytokine and leukocyte infiltration via the inhibition
      of nuclear factor (NF)-kappaB activity in rat lungs. Ruscogenin also attenuated
      MCT-induced endothelial cell apoptosis in the remodeled pulmonary arterioles and
      rescued destruction of endothelial cell membrane proteins such as eNOS, caveolin
      1, and CD31. Our findings suggest that ruscogenin might have therapeutic benefits
      for PAH patients.

PMID- 23538028
TI  - A gene encoding a peptide with similarity to the plant IDA signaling peptide
      (AtIDA) is expressed most abundantly in the root-knot nematode (Meloidogyne
      incognita) soon after root infection.
AB  - Small peptides play important roles in intercellular signaling. Inflorescence
      deficient in abscission (ida) is an Arabidopsis mutant that does not abscise
      (shed) its flower petals. The IDA gene encodes a small, secreted peptide that
      putatively binds to two redundant receptor-like kinases (HAESA and HAESA-like2)
      that initiate a signal transduction pathway. We identified IDA-like (IDL) genes
      in the genomic sequence for Meloidogyne incognita and Meloidogyne hapla. No
      orthologous sequences were found in any other genus of nematodes. Transcript for
      both M. incognita and M. hapla IDLs were found in total RNA isolated from
      infected root systems of tomato, Solanum lycopersicum. Five and three prime RACE
      of RNA from M. incognita infected tomato roots revealed a sequence of 392 nt that
      includes a poly (A) tail of 39 nt. The open reading frame encodes a 47 aa protein
      with a putative 25 aa N-terminal signal peptide. Expression of MiIDL1 is very low
      in eggs and pre-parasitic J2 and rapidly increases in the first four days post
      inoculation (dpi) and then declines at approximately 14 dpi. A proposed role for
      the root-knot nematode IDL is discussed.

PMID- 23538029
TI  - Cell density-dependent ectopic expression in bloodstream form Trypanosoma brucei.
AB  - Ectopic expression of either wild type or mutant proteins is a standard method in
      cell biology, and a vital part of the tool kit of molecular parasitology. During
      study of protein expression levels mediating intracellular trafficking, we became
      aware of highly variable expression between experiments. When investigated
      systematically it became apparent that ectopic expression of proteins from a
      ribosomal promoter diminished at high cell culture density in bloodstream form
      Trypanosoma brucei. This phenomenon was not restricted to expression of a
      specific protein or cell line or the vector backbone. While procyclic form cells
      did not exhibit detectable density-related expression changes, bloodstream form
      cells manifest significant reduction in expression at high density, confirmed by
      qRT PCR, Western blotting and fluorescence microscopy. Culturing in conditioned
      media unveiled a similar reduction in expression at lower cell densities. Taken
      together we concluded that this effect is likely related to the influence of a
      diffusible factor present in conditioned media and has implications for accurate
      quantification of ectopic expression using transgenic expression systems.

PMID- 23538030
TI  - Toxoplasma gondii invasion and replication within neonate mouse astrocytes and
      changes in apoptosis related molecules.
AB  - Toxoplasma gondii invades any nucleated cell, but different replication speed and
      effects on survival/apoptosis processes have been found depending on cell type.
      There are scarce and controversial results regarding the effect of this parasite
      on host cell apoptosis within the brain. The invasion and replication of T.
      gondii RH strain within newborn mouse astrocytes were evaluated in the present
      work. At 4 hpi>90% cells were infected and harbored one to three parasitophorous
      vacuoles with one tazchyzoite/vacuole. Cell culture massive destruction started
      after 24 h of exposure, when the parasite already replicated, with a duplication
      time of around 5 h. The effect of T. gondii infection on apoptosis was also
      evaluated by changes in some anti- and pro-apoptotic markers. At early infection
      times decreased Bcl-2, Survivin and PUMA and increased Noxa expression was found,
      although Survivin and Noxa mRNA levels reverted towards an anti-apoptotic
      phenotype after 6 h. Caspases 3/7 activity decreased three hours after infection,
      although it returned to normal levels thereafter. This enzymatic activity was
      strongly stimulated by Cisplatin (anti-neoplasic drug) but it was inhibited by
      previous T. gondii infection. Likewise, parasite invasion prevented PARP-1
      fragmentation and cell apoptosis induced by the same drug. In conclusion,
      astrocytes seem to activate some apoptosis signals shortly after infection, but
      the parasite takes control of the cell and inhibits programmed death for up to 24
      h, until it replicates, egresses and generates cellular destruction.

PMID- 23538031
TI  - Toxoplasma gondii tachyzoite-infected peripheral blood mononuclear cells are
      enriched in mouse lungs and liver.
AB  - The intracellular parasite Toxoplasma gondii is thought to disseminate throughout
      the host by circulation of tachyzoite-infected leukocytes in the blood, and
      adherence and migration of such leukocytes into solid tissues. However, it is
      unclear whether T. gondii-infected leukocytes can migrate to solid organs via the
      general circulation. In this study, we developed a real-time quantitative PCR
      (qRT-PCR) method to determine the rate of infection of peripheral blood
      mononuclear cells (PBMCs) flowing into and remaining within solid organs in mice.
      A transgenic T. gondii parasite line derived from the PLK strain that expresses
      DsRed Express, and transgenic green fluorescent protein-positive PBMCs, were used
      for these experiments. Tachyzoite-infected PBMCs were injected into mouse tail
      veins and qRT-PCR was used to measure the infection rates of the PBMCs remaining
      in the lungs, liver, spleen and brain. We found that the PBMCs in the lungs and
      liver had statistically higher infection rates than that of the original
      inoculum; this difference was statistically significant. However, the PBMC
      infection rate in the spleen showed no such enhancement. These results show that
      tachyzoite-infected PBMCs in the general circulation remain in the lungs and
      liver more effectively than non-infected PBMCs.

PMID- 23538033
TI  - Autonomic control and bariatric procedures.
AB  - The sudden improvement of metabolic profile and the remission of type 2 diabetes
      after bariatric surgery, well before weight loss, raise important new questions
      regarding glycemic control. Currently, various types of bariatric procedures
      target type 2 diabetes in obese and non-obese patients. Nevertheless, the origin
      of the dramatic metabolic improvements, including glucose homeostasis, is poorly
      understood, and the role of the gastrointestinal (GI) tract remains relatively
      speculative, as well as why these procedures are variably effective. One
      neglected explanation is that such interventions disrupt neural networks
      mediating GI-brain communication and could alter the autonomic output to the
      visceral organs, including the liver. Incretins, e.g., glucagon-like peptide 1
      (GLP-1), have major influence on the central nervous system. Moreover, the level
      of GLP-1 is observed to significantly increase after bariatric surgery and could
      be a key factor in the weight-independent, anti-diabetic effect. Therefore, this
      review will evaluate the effect of GLP-1 on the central nervous system, with
      emphasis on the cellular effects of GLP-1, and will provide an overview of the
      autonomic control of the liver. 

PMID- 23538032
TI  - Estimation of sleep disturbances using wrist actigraphy in patients with postural
      tachycardia syndrome.
AB  - STUDY OBJECTIVES: Patients with postural tachycardia syndrome (POTS) commonly
      complain of fatigue, unrefreshing sleep, daytime sleepiness and diminished
      quality of life. The study objective was to assess sleep quality in POTS patients
      using wrist actigraphy. DESIGN: Prospective study with control group. METHODS:
      Patients with POTS (n = 36) and healthy subjects (n = 36) completed a detailed
      sleep log and actigraphy for 7 days. RESULTS: Compared with healthy subjects,
      POTS patients have more self-reported problems including days with restless sleep
      (53 +/- 30% vs. 21 +/- 20%; P<0.001) and tiredness (75 +/- 23% vs. 39 +/- 27%;
      P<0.001). Using actigraphy, POTS patients have lower sleep efficiency (73 +/- 13%
      vs. 79 +/- 6%; P = 0.01). Actigraphy determined sleep onset latency (SOL) did not
      vary significantly in the two groups, but subjective SOL was higher in POTS
      patient (56 +/- 66 min vs. 1 3 +/- 9 min; P = 0.001). In POTS patients, there was
      a significant correlation between subjective complaints of tiredness and
      actigraphic sleep efficiency (Rs = -0.36; R(2) = 0.15; P = 0.01), significant
      correlations between actigraphic SOL and upright norepinephrine levels (P =
      0.040), and between wake after sleep onset and standing heart rate (P = 0.02).
      CONCLUSIONS: POTS patients have more sleep-related symptoms and poor sleep
      efficiency. The pattern of subjective vs. objective SOL mismatch is suggestive of
      sleep-state misperception. High norepinephrine correlated with actigraphic SOL,
      and this activation of the stress system may contribute significantly to a
      hyperarousal state with consequent insomnia, poor mental and physical health in
      POTS patients.

PMID- 23538034
TI  - Zeranol upregulates corticotropin releasing hormone expression in the placental
      cell line JEG-3.
AB  - Corticotrophin-releasing hormone (CRH) plays a pivotal role in the control of
      parturition in human. Increased amount of plasma CRH is associated with pre
      mature delivery. Zeranol or alpha-zearalanol is a mycotoxin produced by fungi in
      the Fusarium family. Unlike other mycotoxins, exposure to zeranol appears to have
      minimal health risk. In North America, it is used as a growth-promoting agent in
      livestock. Because of the health concern of zeranol residue in meat, this
      practice has not been adopted in Europe. In our study zeranol could induce CRH
      protein expression in JEG-3 cells as low as 0.1nM. As electrophoretic mobility
      shift assay indicated an increase in the CRE binding activity in CRH promoter,
      the induction was likely triggered by transcriptional regulation. We further
      looked into the signal transduction pathway and PKCdelta and ERK-1/2 were found
      to be activated. This study showed that zeranol could increase CRH expression in
      placental cells, and the findings might be a concern for pregnant women.

PMID- 23538035
TI  - The conjugation of microcystin-RR by human recombinant GSTs and hepatic cytosol.
AB  - Many cyanobacterial species can produce cyanotoxins, among which mycrocistins
      (MC) are a group of ~100 congeners of hepatotoxic cyclic heptapeptides. MC-RR
      differs from MC-LR, the most studied congener only for one residue (arginine vs
      leucine), resulting in a ten-fold difference in the acute toxicity in mice.
      Although humans may be exposed to MC through several routes and kinetics appeared
      to be the major factor affecting congener-specific toxicity, little is known on
      MC metabolism. The accepted pathway for MC detoxication is GSH conjugation: here
      the MC-RR conjugation with GSH catalyzed by 5 recombinant human GSTs and human
      liver cytosol (HLC) has been characterized and appeared to be more efficient than
      MC-LR conjugation. The catalytic efficiency score is T1-1>A1-1~P1-1>M1-1>A3-3
      (0.161-0.056pmol GSMC-RR (MUgproteinminMUM)(-1)). In HLC the spontaneous reaction
      is favored vs the enzymatic one (ratio 3:1) at physiological GSH content.
      However, at low MC-RR concentrations, representative of repeated oral exposure,
      and low GSH content (down to 0.05mM), possibly associated to exposure to drugs or
      in patients affected by several pathologies, the relevance of the enzymatic
      reaction progressively increases, providing the predominant contribution to MC-RR
      detoxication.

PMID- 23538036
TI  - Apoptotic and proinflammatory effect of combustion-generated organic
      nanoparticles in endothelial cells.
AB  - Air pollution exposure in industrialized cities is associated with an increased
      risk of morbidity and mortality attributed to cardiovascular diseases. Combustion
      exhausts emitted from motor vehicles and industries represent a major source of
      nanoparticles in the atmosphere. Flame-generated organic carbon nanoparticles (OC
      NPs) provide interesting model nanoparticles that simulate fresh combustion
      emissions near roadways or combustion sources. These model nanoparticles can be
      produced by controlling flame operating conditions and used to test possible
      toxicological mechanisms responsible for the observed health effects. OC NPs were
      used to investigate their possible effect on endothelial cells (EC) growth and
      production of proinflammatory lipid mediators. Results indicated a dose and time
      dependent reduction in cell viability following incubation of EC with OC NPs for
      24 and 48h. Fluorescence-activated cell sorting revealed that EC treated with OC
      NPs showed a cell proliferation index significantly lower than that of control
      cells and an increased apoptotic cell death. The annexin assay confirmed the
      increased apoptotic cell death. Moreover, OC NPs also induced a time-dependent
      increase of proinflammatory lysophospholipid production. These results,
      establishing that OC NPs induce EC proinflammatory lysophosholipid production and
      apoptotic cell death, provide the first evidence of the detrimental effect of OC
      NPs on EC.

PMID- 23538037
TI  - Development of a strand specific SYBRGreen RT-PCR for a GIII.2 bovine norovirus.
AB  - A strand specific SYBRGreen RT-PCR was developed for a bovine norovirus (GIII.2).
      HEK293 cells were transfected with a plasmid containing the complete virus genome
      and copy DNA was produced with viral RNA strand-specific primers that introduced
      nucleotide changes. Amplicons from the negative and positive viral RNA strands,
      and from potential transcripts made by sequence independent transcription, were
      separated by melting curve analysis. The RT-PCR showed high strand specificity
      and could be a useful tool to study virus replication in replicon and reverse
      genetic systems and in screening for low levels of virus replication in norovirus
      permissive cell lines.

PMID- 23538038
TI  - Comparative evaluation of conventional polymerase chain reaction (PCR), with loop
      mediated isothermal amplification and SYBR green I-based real-time PCR for the
      quantitation of porcine circovirus-1 DNA in contaminated samples destined for
      vaccine production.
AB  - Porcine circovirus type1 (PCV1), described initially as a contaminant of a
      porcine kidney cell line, is ubiquitous within the swine population The presence
      of PCV1 in porcine cell lines can lead to contamination during both human and
      porcine vaccine production. Therefore, a rapid, specific, sensitive and practical
      method is needed for the detection of PCV1 in bio-products. The aim of this study
      was to compare three assays in their ability to accurately quantify PCV1 virus in
      biological samples, namely loop-mediated isothermal amplification (LAMP), SYBR
      green I-based real-time polymerase chain reaction (PCR) and conventional PCR. All
      assays yielded successful quantitation of PCV1 DNA and differentiated between
      PCV1-free and-contaminated cells. In addition, the results were specific for
      PCV1, since amplification of samples containing closely-related PCV2 or other
      pathogenic swine viruses yielded negative results. The lowest detection threshold
      of 10(2) copies was displayed by the SYBR green I-based real-time PCR assay. In
      addition, this assay was the most effective in detecting PCV1 contamination in a
      set of commercially available porcine vaccines. Therefore we conclude that SYBR
      green I-based real-time PCR is specific and sensitive for detecting PCV1 in
      biological samples and maybe used for quality control of vaccine and biomaterial
      production.

PMID- 23538039
TI  - Rapid field assessment of RO desalination of brackish agricultural drainage
      water.
AB  - Rapid field evaluation of RO feed filtration requirements, selection of effective
      antiscalant type and dose, and estimation of suitable scale-free RO recovery
      level were demonstrated using a novel approach based on direct observation of
      mineral scaling and flux decline measurements, utilizing an automated Membrane
      Monitor (MeMo). The MeMo, operated in a stand-alone single-pass desalting mode,
      enabled rapid assessment of the adequacy of feed filtration by enabling direct
      observation of particulate deposition on the membrane surface. The diagnostic
      field study with RO feed water of high mineral scaling propensity revealed (via
      direct MeMo observation) that suspended particulates (even for feed water of
      turbidity <1 NTU) could serve as seeds for promoting surface crystal nucleation.
      With feed filtration optimized, a suitable maximum RO water recovery, with
      complete mineral scale suppression facilitated by an effective antiscalant dose,
      can be systematically and directly identified (via MeMo) in the field for a given
      feed water quality. Scale-free operating conditions, determined via standalone
      MeMo rapid diagnostic tests, were shown to be applicable to spiral-would RO
      system as validated via both flux decline measurements and ex-situ RO plant
      membrane scale monitoring. It was shown that the present approach is suitable for
      rapid field assessment of RO operability and it is particularly advantageous when
      evaluating water sources of composition that may vary both temporally and across
      the regions of interest.

PMID- 23538040
TI  - [Brachytherapy for cutaneous and lip carcinomas].
AB  - Cutaneous basal or squamous cell carcinomas are frequent lesions, their prognosis
      being associated to local control. Surgery remains the standard of treatment, if
      a complete resection can be realized without impairment of cosmesis or function.
      Brachytherapy can be used in the other cases, and is especially well adapted to
      periorificial lesions of the face. It is mostly realized with low dose rate
      iridium wires, but can be done with high dose rate if outpatient treatment is
      preferred. It allows high local control rates with very few late complications.
      The indication has to be discussed as first line treatment, according to the
      patient's age and general condition, the characteristics of the lesion, and the
      risk of late cosmetic or functional side-effects of the different therapeutic
      options.

PMID- 23538041
TI  - Local recurrence after ductal carcinoma in situ breast conserving treatment.
      Analysis of 195 cases.
AB  - PURPOSE: Ductal carcinoma in situ overall prognosis is excellent, but after
      breast conserving surgery, with or without radiotherapy, local recurrences can
      lead to locoregional or distant evolution and death. However, there are few data
      on optimal local recurrences treatment and long-term impact on survival. PATIENTS
      AND METHODS: This study included 195 women treated from 1985 to 1996 by
      conservative surgery (CS) or conservative surgery followed by radiotherapy
      (CS+RT), presenting local recurrences, with a 156-month median follow-up.
      RESULTS: Eighty-two out of 195 (42%) local recurrences were non-invasive (in
      situ) and 113 (58%) invasive. In situ local recurrence was discovered by
      mammography in 80.5% of the cases versus 47.5% for invasive local recurrence
      (P=0.0001). Salvage mastectomy was used in 53% of the cases after conservative
      surgery and 75% after conservative surgery followed by radiotherapy. The axillary
      nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in
      situ and invasive local recurrences. Among 113 patients with invasive local
      recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%)
      developed metastases, respectively. Among invasive local recurrences,
      comedocarcinoma subtype was highly predictive of subsequent metastases (32%
      versus 4.4%, P<0.0007). CONCLUSION: Invasive local recurrence after ductal
      carcinoma in situ treatment could be a dramatic event, fully changing long-term
      prognosis. Early mammographic local recurrence diagnosis (if possible still at
      non-invasive stage) seems essential to avoid or minimize metastatic risk.
      Mastectomy remains the safest option but, in some cases, a new conservative
      approach could be discussed.

PMID- 23538042
TI  - Fluoroscopic radiation exposure during hip arthroscopy.
AB  - PURPOSE: The purpose of this study was to assess the maximal dose area product
      (DAP) of radiation received by women during hip arthroscopy; we used computer
      modeling to determine the theoretical risk to a fetus. METHODS: We studied 116
      female patients of childbearing age who underwent hip arthroscopy. We
      retrospectively collected data from the procedure, hip pathologic process, and
      dose of irradiation in milligray. We calculated the theoretical dose of radiation
      to the fetus and the risk of childhood hereditary disease and cancer. RESULTS:
      Labral tear (52%) was the most common indication for hip arthroscopy, with labral
      resection the most common procedure undertaken. The maximal DAP to the patient
      was 9.52 mGy, and the maximal DAP was estimated to be 2.99 mGy to the fetus. The
      risk of hereditary disease and childhood cancer for the fetus was calculated to
      be 1 in 14,000 and 1 in 11,000, respectively. CONCLUSIONS: Fluoroscopy used in
      hip arthroscopy generates a maximal theoretical dose of 2.99 mGy to the fetus,
      which places the procedure in the low-risk category. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 23538043
TI  - Technical difficulties and their prediction in 2-portal endoscopic carpal tunnel
      release for idiopathic carpal tunnel syndrome.
AB  - PURPOSE: This study aimed to identify technical difficulties encountered during 2
      portal endoscopic carpal tunnel release (ECTR) and to determine their incidence.
      Furthermore, we assessed the possibility of preoperatively predicting such
      technical difficulties. METHODS: We retrospectively reviewed the records of 311
      hands of 311 patients with idiopathic carpal tunnel syndrome who underwent ECTR
      with our modified Chow 2-portal technique. Any technical difficulties during the
      procedure were reviewed and correlated with preoperative physical findings, nerve
      conduction studies, and magnetic resonance imaging findings, by use of the t
      test, chi(2) test, and binary regression analysis. RESULTS: One or more
      difficulties were encountered in 139 of 311 hands (44.7%), whereas surgery in the
      remaining 172 hands (55.3%) was performed without any difficulties. Technical
      difficulties encountered were as follows: tight access in 61 hands, difficulty in
      identifying the distal part of the transverse carpal ligament through the exit
      portal in 35 hands, synovial tissue being caught at the cannula tip when pulling
      it out of the carpal tunnel in 39 hands, steep angle of the cannula assembly with
      difficulty in emerging from the exit portal in 29 hands, and other difficulties.
      Postoperative worsening of symptoms was observed in 8 hands (2.6%), in all of
      which technical difficulties were encountered. Tight access was noted in younger
      patients and those with a small cross-sectional area at the hook-of-hamate level.
      The entire ECTR procedure for older female patients was more likely to be easily
      performed. CONCLUSIONS: The surgeon may face a variety of technical difficulties
      during ECTR. Technical difficulties were most often encountered during
      introduction of the cannula assembly into the carpal tunnel and pulling it out of
      the exit portal. Older female patients may be the best candidates for 2-portal
      ECTR. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 23538044
TI  - Femoral tunnel position on conventional magnetic resonance imaging after anterior
      cruciate ligament reconstruction in young men: transtibial technique versus
      anteromedial portal technique.
AB  - PURPOSE: The purpose of this study was to compare clinical outcomes after single
      bundle anterior cruciate ligament (ACL) reconstruction with a free Achilles
      tendon allograft using either a transtibial or an anteromedial portal technique
      and then to quantify the difference in femoral tunnel position between these 2
      approaches. This assessment was to be performed with a new method using
      conventional magnetic resonance imaging (MRI) with a digital imaging system.
      METHODS: In this prospective randomized comparative study, 53 young male patients
      with ACL rupture underwent ACL reconstruction with the transtibial technique
      (group 1) or the anteromedial portal technique (group 2). We assessed clinical
      outcomes with the Lachman test, pivot shift test, International Knee
      Documentation Committee (IKDC) classification, Lysholm score, Tegner activity
      scale, and single leg hop (SLH) test. Radiologic assessments included the
      position of the femoral tunnel aperture and the posterior cruciate ligament (PCL)
      index on conventional MRI and the side-to-side difference (SSD) on stress
      radiographs. RESULTS: Sixty-one participants had follow-up. The mean follow-up
      period was 30.2 months. At the last follow-up, there were no significant
      differences between the 2 groups in results from the Lachman test, pivot shift
      test, IKDC classification, Tegner activity scale, and SLH test. The Lysholm score
      and SSD results in group 2 were superior to those in group 1 (P < .001). The
      femoral tunnel aperture was positioned more posteriorly in group 2 than in group
      1 (P < .001). Changes in the PCL index were greater in group 1 than in group 2 (P
      < .001). CONCLUSIONS: The position of the femoral tunnel aperture created with
      the anteromedial portal technique was more posterior than that made with the
      transtibial technique. Knees reconstructed with the anteromedial portal technique
      were more stable in Telos testing, and were 3 points higher on the Lysholm score.
      However, there were no statistically significant differences in the Tegner
      activity scale or IKDC classification between the 2 groups. LEVEL OF EVIDENCE:
      Therapeutic level I, randomized controlled clinical trial.

PMID- 23538045
TI  - Introduction: Taste perception.

PMID- 23538046
TI  - Reduced expression of SM22 is correlated with low autophagy activity in human
      colorectal cancer.
AB  - Colorectal cancer (CRC) is a common malignancy with a high incidence and
      mortality rate. Recent studies have pointed to deregulation of autophagy as a
      novel pathogenesis of human malignancy. SM22 is considered as a tumor suppressor.
      The aim of the present study was to evaluate the correlation of the SM22
      expression level with the autophagy activity and the clinical characteristics in
      human CRC tissues. The expressions of SM22 and p62, a biomarker of autophagy
      activity, in paired tumor and adjacent non-tumor tissues from 43 patients with
      colorectal cancer were detected by western blot and immunohistochemical staining,
      respectively. The results showed that the SM22 level decreased significantly in
      81.4% CRC tissues, while the expression of p62 increased in 79.1% cases. There
      was a negative correlation between p62 and SM22 expressions in colorectal cancer
      tissues (p=0.004). Similarly, the negative correlation between SM22 and p62 was
      verified in human CRC cell lines. The data suggest that the autophagy activity
      decreased in human CRC, which was associated with reduction in SM22 expression.
      However, the expression of SM22 was not associated with the gender, tumor site
      and Duke's stage of the patients. In conclusion, our findings suggest that the
      disruption of SM22 may be involved in tumorigenesis in CRC. The autophagic
      activity may be suppressed in human CRC, and SM22 may act as a positive regulator
      in the processes of autophagy.

PMID- 23538047
TI  - Mutation analysis of KRAS in primary colorectal cancer and matched metastases by
      means of highly sensitivity molecular assay.
AB  - Mutation analysis of KRAS is needed before starting treatment with anti-EGFR
      monoclonal antibodies in patients with metastatic colorectal cancer (CRC). In
      most of the cases, testing is performed on primary tumors, assuming that KRAS
      mutation status does not change in metastasis although correlation studies gave
      conflicting results. We evaluated the KRAS status concordance rate between
      primary tumors and related metastasis using a highly sensitive molecular assay.
      Forty-five primary tumors and related metastases from patients with CRC (28/45
      male-62.2% and 17/45 female-37.8%; mean age 66.4 years) were analyzed by using
      TheraScreen: KRAS mutational kit. Metastatic samples were collected from lymph
      nodes (8/45-17.8%) and visceral sites (37/45-82.2%); 23 were synchronous (49%)
      and 22 were metachronous (51%), obtained after a mean of 30.8 months after the
      first diagnosis of CRC. Twenty-eight patients had KRAS mutations in both primary
      CRC and related metastases (62.2%). No differences in type and frequency of
      mutations were identified, despite different metastatic sites and time of onset
      of metastatic disease. Our results indicate that the mutation status of KRAS is
      the same in primary CRC and metastasis, suggesting that in clinical practice,
      KRAS testing can be performed on both tumor tissues when using a highly sensitive
      molecular assay.

PMID- 23538048
TI  - Speaking French: will it be a shared opportunity for scientific communication in
      PMR?

PMID- 23538049
TI  - 18FDG-PET/CT for the detection of regional nodal metastasis in patients with
      primary head and neck cancer before treatment: a meta-analysis.
AB  - BACKGROUND: We performed a meta-analysis to evaluate the role of (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG
      PET/CT) in the detection of regional nodal metastasis in patients with primary
      head and neck cancer before treatment. MATERIALS AND METHODS: Studies about
      (18)FDG-PET/CT for the detection of regional nodal metastasis in patients with
      primary HNC were systematically searched in the MEDLINE, EMBASE, and EBM Review
      databases from January 1, 2000 to July 25, 2012. A software called "Stata 12.0"
      was used to obtain pooled estimates of sensitivity, specificity, positive
      likelihood ratio, and negative likelihood ratio for PET/CT. We also calculated
      hierarchic summary receiver operating characteristic (HSROC) curves and area
      under the curves. RESULTS: 14 articles (742 patients) fulfilled all inclusion
      criteria. The pooled sensitivity, and specificity with 95% confidence interval
      for PET/CT on a per-neck-side analysis were 0.84 (0.77-0.89) and 0.84 (0.78
      0.89). The corresponding values for PET/CT on a per-nodal-level analysis 0.84
      (0.78-0.88) and 0.96 (0.94-0.98). CONCLUSIONS: (18)FDG-PET/CT had good diagnostic
      performance for the detection of regional nodal metastasis in patients with
      primary head and neck cancer before treatment.

PMID- 23538050
TI  - Adsorption kinetics of silicic acid on akaganeite.
AB  - As part of a series of studies on the interaction between ferric ions and silicic
      acid in the hydrosphere, the adsorption of silicic acid on akaganeite was
      investigated kinetically at various pH values. The adsorption of silicic acid
      increased with increasing pH over an initial pH range of 4-11.5. In the kinetic
      experiment, the Cl(-) was released from akaganeite much faster than silicic acid
      was adsorbed. From this result, we concluded that chloride ions bound on the
      surface of akaganeite are released and Fe-OH or Fe-O(-) sites are formed, which
      then acts as an adsorption site for silicic acid. The uptake mechanism of silicic
      acid by akaganeite is significantly different from that by schwertmannite,
      despite the presence of the same tunnel structure.

PMID- 23538051
TI  - UV-Vis and NMR study of the formation of gold nanoparticles by citrate reduction:
      observation of gold-citrate aggregates.
AB  - The citrate reduction of gold(III) in water is one of the most commonly used
      synthetic pathways for the preparation of gold colloids. In order to gain insight
      into the formation of gold nanoparticles (GNPs) using this method, the synthesis
      of GNPs was undertaken under different experimental conditions and monitored in
      operando by UV-Vis spectroscopy. These experiments highlight that citrate should
      be polydeprotonated and that Au(III) should not be polyhydroxylated in order to
      obtain GNPs with a narrow size distribution. Samples taken during the reaction
      were also characterized by Nuclear Magnetic Resonance Spectroscopy (NMR) to
      monitor the various reaction products as a function of time. Diffusion Ordered
      SpectroscopY (DOSY) experiments allowed us to identify slow diffusing citrate -
      Au(I) or Au(0) complexes which could play a role in the formation of GNPs.

PMID- 23538052
TI  - Women with atrial fibrillation in Qatar with special reference to gender
      difference: caution on the representativeness of non-Caucasian countries.

PMID- 23538054
TI  - Assessment of diagnostic accuracy of a commercial ELISA for the detection of
      Toxoplasma gondii infection in pigs compared with IFAT, TgSAG1-ELISA and Western
      blot, using a Bayesian latent class approach.
AB  - Serological methods are the most commonly used diagnostic tools to detect
      Toxoplasma gondii infections in pigs. In the absence of a readily available 'gold
      standard', an estimation of diagnostic accuracy is difficult to assess. A
      commercial ELISA (PrioCHECK(r) Toxoplasma Ab porcine ELISA, Prionics, Schlieren,
      Switzerland) for the diagnosis of T. gondii infection in pigs was evaluated in
      naturally infected animals from two distinct populations; indoor and outdoor
      living animals. An assessment of diagnostic accuracy, using a Bayesian latent
      class approach with adjustment for within indoor and outdoor farm clustering
      using random effects, was performed. Tests used for comparison were: IFAT; ELISA
      using native affinity-purified P30 (SAG1) T. gondii tachyzoite surface antigen
      (TgSAG1-ELISA); and Western blot with T. gondii tachyzoites lysate. The data set
      comprised 297 pig serum samples across outdoor (n=149) and indoor (n=148) farms
      in Argentina. The estimated sensitivity and specificity for the commercial ELISA
      were 98.9% (95% credible interval: 96.2; 100) and 92.7% (95% credible interval:
      87.7; 96.6), respectively. The analysis of sera and plasma from pigs (n=6)
      experimentally inoculated with 5,000 T. gondii oocysts revealed a pronounced
      antibody response beginning 2 weeks p.i. until the end of the observation period
      (11 weeks p.i.) in all animals. Meat juice obtained from inoculated animals after
      euthanasia also tested positive. These results suggest that the PrioCHECK(r)
      Toxoplasma Ab porcine ELISA may be a useful tool to perform serological diagnosis
      of T. gondii infections in pigs to control Toxoplasma infection in pigs and
      humans.

PMID- 23538053
TI  - Incremental value of biomarkers to clinical variables for mortality prediction in
      acutely decompensated heart failure: the Multinational Observational Cohort on
      Acute Heart Failure (MOCA) study.
AB  - AIM: This study aims to evaluate the incremental value of plasma biomarkers to
      traditional clinical variables for risk stratification of 30-day and one-year
      mortality in acutely decompensated heart failure (ADHF). METHODS AND RESULTS:
      Through an international collaborative network, individual patient data on 5306
      patients hospitalized for ADHF were collected. The all-cause mortality rate was
      11.7% at 30 days and 32.9% at one year. The clinical prediction model (age,
      gender, blood pressure on admission, estimated glomerular filtration rate <60
      mL/min/1.73 m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic
      of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers
      measured at presentation improved risk stratification when added to the clinical
      model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid
      regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2
      (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal
      pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial
      natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%)
      and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05
      for all). CRP also markedly improved risk stratification of patients with ADHF as
      a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30
      days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). CONCLUSION: In
      this study, biomarkers provided incremental value for risk stratification of ADHF
      patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP,
      reflecting different pathophysiologic pathways, add prognostic value to clinical
      risk factors for predicting both short-term and one-year mortality in ADHF.

PMID- 23538055
TI  - [Athlete's heart in the young: electrocardiographic and echocardiographic
      patterns in 107 French athletes].
AB  - PURPOSE: Since 2009 in France, every people practicing sport in competition must
      have a cardiovascular exam with electrocardiogram, to prevent sudden cardiac
      death. Sometimes, an echocardiography will be necessary. Little is known about
      athlete's heart in the young, particularly in the French people. PATIENTS AND
      METHODS: One hundred and seven French elite adolescent athletes had an
      electrocardiogram with echocardiography to establish reference values in this
      population. RESULTS: QTcorrected (QTc) interval calculated by the Hodges formula,
      is always in the normal values. Interventricular septal thickness is always <= 11
      mm and left ventricular end diastolic diameter <= 55 mm in about 90 % of the
      athletes. Females have QTc interval longer than males and interventricular septal
      thickness finer. Diastolic function (18.9 +/- 2.6 cm/s for e', E/e' ratio at 5.3
      +/- 0.8) is "supernormal" and correlate with age and cardiac frequency. Right
      ventricular systolic function is always good. CONCLUSION: Adolescent athlete's
      heart is normal. If QTc interval is not normal, be afraid of a QT long syndrome.
      Furthermore, when interventricular septal thickness is > 11 mm or left
      ventricular end diastolic diameter > 55 mm, myocardiopathy will have to be ruled
      out.

PMID- 23538056
TI  - Microbial community analysis of swine wastewater anaerobic lagoons by next
      generation DNA sequencing.
AB  - Anaerobic lagoons are a standard practice for the treatment of swine wastewater.
      This practice relies heavily on microbiological processes to reduce concentrated
      organic material and nutrients. Despite this reliance on microbiological
      processes, research has only recently begun to identify and enumerate the myriad
      and complex interactions that occur in this microbial ecosystem. To further this
      line of study, we utilized a next-generation sequencing (NGS) technology to gain
      a deeper insight into the microbial communities along the water column of four
      anaerobic swine wastewater lagoons. Analysis of roughly one million 16S rDNA
      sequences revealed a predominance of operational taxonomic units (OTUs)
      classified as belonging to the phyla Firmicutes (54.1%) and Proteobacteria
      (15.8%). At the family level, 33 bacterial families were found in all 12 lagoon
      sites and accounted for between 30% and 50% of each lagoon's OTUs. Analysis by
      nonmetric multidimensional scaling (NMS) revealed that TKN, COD, ORP, TSS, and DO
      were the major environmental variables in affecting microbial community
      structure. Overall, 839 individual genera were classified, with 223 found in all
      four lagoons. An additional 321 genera were identified in sole lagoons. The top
      25 genera accounted for approximately 20% of the OTUs identified in the study,
      and the low abundances of most of the genera suggests that most OTUs are present
      at low levels. Overall, these results demonstrate that anaerobic lagoons have
      distinct microbial communities which are strongly controlled by the environmental
      conditions present in each individual lagoon.

PMID- 23538057
TI  - Enterotoxigenic Bacteroides fragilis causes lethal colitis in Mongolian gerbils.
AB  - Enterotoxigenic Bacteroides fragilis (ETBF) causes inflammatory diarrhea in
      humans and livestock and is implicated in colorectal cancer. In this report, we
      show for the first time that ETBF can induce profuse diarrhea and an acute,
      lethal colitis in Mongolian gerbils.

PMID- 23538058
TI  - Repeatability and reproducibility of choroidal vessel layer measurements in
      diabetic retinopathy using enhanced depth optical coherence tomography.
AB  - PURPOSE: To describe novel segmentation protocols for choroidal layers, Sattler's
      medium and Haller's large vessel layers, using enhanced depth imaging optical
      coherence tomography (EDI-OCT), and to examine the repeatability and
      reproducibility of these measurements in eyes with diabetic retinopathy. METHODS:
      Fifty-one patients with Type 2 diabetes mellitus were imaged using custom EDI
      scanning protocols. Detailed segmentation was performed to quantify the retina,
      choroid, Haller's large, and Sattler's medium vessel layers in the total macular
      circle (TMC) and foveal central subfield (FCS). The coefficient of repeatability
      (CR) and intraclass correlation coefficient (ICC) were used as a measure of
      repeatability and relative reliability within graders. Reproducibility or
      interobserver variability was assessed using Bland-Altman plots and 95% limits of
      agreement (LoA). RESULTS: Intragrader CR of the retina, choroid, Sattler's, and
      Haller's layers for thickness measurements were 19.2, 26.9, 35.2, and 29.2 MUm,
      respectively. Intergrader 95% LoA were 27.9, 41.5, 38.6, 31.1 MUm (thickness),
      respectively. Choroidal sublayer measurements showed good intraobserver
      reliability (ICC 0.78-0.98). Interobserver variability for retinal and choroidal
      measurements was not significantly different (P > 0.45). Measurements from the
      TMC showed slightly better repeatability and agreement compared with the FCS
      alone. Mean intergrader differences were reduced after training, and were most
      apparent in choroidal sublayers. CONCLUSIONS: The choroidal vascular sublayers
      can be quantified with good reliability, repeatability, and reproducibility.
      Accurate quantitative assessment of these sublayers may provide new insights into
      the role of the choroid in visual loss in patients with diabetic retinopathy, and
      prove useful for future clinical trials.

PMID- 23538059
TI  - Associations of iris structural measurements in a Chinese population: the
      Singapore Chinese Eye Study.
AB  - PURPOSE: We determined the ocular biometric and demographic factors associated
      with iris parameters in Singaporean Chinese persons from a population-based
      sample. METHODS: Subjects were participants in the Singapore Chinese Eye Study, a
      population-based cross-sectional study of eye disease. Anterior segment optical
      coherence tomography images were analyzed using customized software to measure
      iris thickness at 750 MUm from the scleral spur (IT750), iris area (I-Area), and
      iris curvature (I-Curv). Regression analyses were performed to assess the
      association between iris measurements with a range of demographic and ocular
      variables. The contribution of each independent variable to the iris parameter of
      interest was determined sequentially using a stepwise selection algorithm.
      RESULTS: We included 1473 participants with a mean age of 57.7 + 8.68 years, and
      50.6% were men. The mean IT750, I-Area, and I-Curv were 0.46 +/- 0.10 mm, 1.49 +/
      0.24 mm(2), and 0.25 +/- 0.13 mm, respectively. Statistical regression models,
      including a range of demographic and ocular parameters, explained 59.3%, 41.9%,
      and 34.3% of the variability in I-Curv, IT750, and I-Area, respectively. Angle
      opening distance at 750 MUm from the scleral spur (AOD750) was the single factor
      associated most strongly with I-Curv, and explained 46.6% of its variation.
      CONCLUSIONS: A significant proportion of the variation in iris area, curvature,
      and thickness was not explained by other ocular and demographic parameters. Iris
      curvature was associated strongly with angle width, and of all parameters
      investigated, AOD750 was most highly correlated with iris curvature.

PMID- 23538060
TI  - Comparative analysis of repeatability of manual and automated choroidal thickness
      measurements in nonneovascular age-related macular degeneration.
AB  - PURPOSE: We compared the reproducibility and mutual agreement of the subfoveal
      choroidal thickness measurements by expert raters and an automated algorithm in
      enhanced depth imaging optical coherence tomography (EDI-OCT) images of eyes with
      nonneovascular age-related macular degeneration (AMD). METHODS: We recruited 44
      patients with nonneovascular AMD and EDI-OCT images were acquired. Subfoveal
      choroidal thickness was measured manually by two expert raters and automatically
      by a graph-cut-based algorithm. Drusen area was measured using the automated
      software (version 6) of Cirrus SD-OCT. The manual and automated choroidal
      thickness measurements were compared in reproducibility, mutual agreement, and
      correlation with drusen area. RESULTS: The mean subfoveal choroidal thickness was
      246 +/- 63 MUm for the first rater, 214 +/- 68 for the second rater, and 209 +/-
      53 for the automated algorithm. Intraclass correlation coefficients (ICC) and 95%
      confidence intervals (CI) were 0.96 (CI 0.94-0.98) between the raters, 0.85 (CI
      0.77-0.90) between the first rater and the automated algorithm, and 0.84 (CI 0.75
      0.89) between the second rater and the automated algorithm. Repeat scan
      measurement ICCs were 0.91 (CI 0.86-0.94) for the first rater, 0.96 (CI 0.94
      0.97) for the second rater, and 0.87 (CI 0.80-0.92) for the automated algorithm.
      Manual and automated measurements were correlated with drusen area. CONCLUSIONS:
      The automated algorithm generally yielded smaller choroidal thickness than the
      raters with a moderate level of agreement. However, its repeat scan measurement
      repeatability was comparable to that of the manual measurements. The mean
      difference between the raters indicated possible biases in different raters and
      rating sessions. The correlation of the automated measurements with the drusen
      area was comparable to that of the manual measurements. Automated subfoveal
      choroidal thickness measurement has potential use in clinical practice and
      clinical trials, with possibility for reduced time and labor cost.

PMID- 23538061
TI  - Automated analysis of binocular alignment using an infrared camera and selective
      wavelength filter.
AB  - PURPOSE: We present a computerized method of measuring binocular alignment using
      a selective wavelength filter and an infrared camera, and validate the efficacy
      of automated image analysis compared to the gold standard prism and alternate
      cover test (PCT). METHODS: A prospective observational pilot study was performed
      on 30 subjects with intermittent exotropia, 30 subjects with esotropia, and 30
      orthotropic subjects who were able to cooperate with the PCT. Two independent
      ophthalmologists examined the angle of deviation using the PCT. Full-face images
      were obtained with an infrared camera while a selective wavelength filter was
      placed in front of either eye. Images were analyzed using the 3D Strabismus Photo
      Analyzer. Interobserver variability, test-retest reliability and correlation
      between the angles of deviation were determined for both methods. RESULTS: The
      95% limit of agreement of interobserver variability was +/- 4.8 prism diopters
      (PD) for the PCT and +/- 4.3 PD for the selective wavelength filter analysis. The
      95% limit of agreement of test-retest reliability between the PCT and selective
      wavelength filter analysis was +/- 8.5 PD. Results of the PCT and selective
      wavelength filter analysis showed a strong positive correlation (R = 0.900, P <
      0.001). CONCLUSIONS: Infrared images acquired with a selective wavelength filter
      can detect the latent components of strabismus, and automated image analysis
      showed excellent agreement with the standard PCT. This automated method is an
      accurate and reliable tool for measuring ocular deviation with minimal observer
      dependency.

PMID- 23538062
TI  - Wavelength optimization in femtosecond laser corneal surgery.
AB  - PURPOSE: To evaluate the influence of wavelength on penetration depth and quality
      of femtosecond laser corneal incisions in view of optimizing procedures in
      corneal surgery assisted by ultrashort pulse lasers. METHODS: We performed
      penetrating and lamellar incisions on eye bank corneas using several ultrashort
      pulse laser sources. Several wavelengths within the near-infrared and shortwave
      infrared wavelength range were used and the pulse energy was varied. The corneas
      were subsequently analyzed using light microscopy as well as transmission and
      scanning electron microscopy. RESULTS: We found higher penetration depths and
      improved incision quality when using wavelengths close to lambda = 1650 nm rather
      than the wavelength of lambda = 1030 nm typical in current clinical systems.
      Optical micrographs show an improvement of the penetration depth by a factor of 2
      to 3 while maintaining a good incision quality when using the longer wavelength.
      These results were confirmed with micrographs obtained with transmission and
      scanning electron microscopy. CONCLUSIONS: A wavelength change from the standard
      1030 nm to 1650 nm in corneal surgery assisted by ultrashort pulse laser
      considerably reduces light scattering within the tissue. This results in a better
      preservation of the laser beam quality in the volume of the tissue, particularly
      when working at depths required for deep lamellar or penetrating keratoplasty.
      Using this wavelength yields improved penetration depths into the tissue; it
      permits use of lower energies for any given depth and thus reduces unwanted side
      effects as thermal effects.

PMID- 23538063
TI  - [Gly14]-Humanin offers neuroprotection through glycogen synthase kinase-3beta
      inhibition in a mouse model of intracerebral hemorrhage.
AB  - Perihematomal brain edema formation and consequent cell death contribute to
      second brain injury resulting in severe neurological deficits and sometimes
      delayed fatality after intracerebral hemorrhage (ICH). [Gly14]-Humanin (HNG), a
      variant of Humanin (HN) in which the 14th amino acid serine is replaced with
      glycine, reduced Alzheimer's disease-relevant insults and improved neurological
      deficits in an ischemia stroke model. In the study, we aimed to evaluate whether
      HNG posttreatment attenuated early brain injury after ICH and whether the
      protective effect was associated with regulation of apoptosis via
      phosphatidylinositol 3-kinase (PI3K)-Akt/GSK-3beta signaling. Male ICR mice were
      subjected to infusion of Type IV collagenase (to induce ICH) of saline (for
      shams) into the left striatum. ICH animals received vehicle, HNG (1 or 2.5 MUg in
      100 MUl saline) administration intraperitoneally 1h post injury. Compared with
      vehicle, HNG-2.5 MUg treatment improved neurological outcome and reduced brain
      edema at 24 and 72 h after surgery (P<0.05), but wortmannin (15 MUg/kg, 90 min
      before HNG-2.5 MUg, intravenously) obliterated the effect. HNG-2.5 MUg also
      reduced cell insults and injury volume at 24 and 72 h after surgery (P<0.05, vs.
      vehicle). Furthermore, HNG-2.5 MUg treatment increased p-Akt and Bcl-2 and
      decreased p-GSK-3beta, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase
      expressions in the ipsilateral hemisphere (P<0.05, vs. vehicle), however, the
      effect was reversed by wortmannin. In conclusion, HNG treatment improved
      functional and morphological outcomes after experimental ICH in mice and the
      protective effect was associated with suppressing apoptosis through PI3K-Akt/GSK
      3beta signaling pathway.

PMID- 23538064
TI  - Dopamine D1 receptors are not critical for opiate reward but can mediate opiate
      memory retrieval in a state-dependent manner.
AB  - Although D1 receptor knockout mice demonstrate normal morphine place preferences,
      antagonism of basolateral amygdala (BLA) D1 receptors only during drug-naive rat
      conditioning has been reported to inhibit the expression of a morphine place
      preference. One possible explanation for this result is state-dependent learning.
      That is, the omission of the intra-BLA infusion cue during testing - which acts
      as a potent discriminative stimulus - may have prevented the recall of a morphine
      environment association and therefore, the consequent expression of a morphine
      place preference. To examine this possibility, we tested whether intra-BLA
      infusion of the D1-receptor antagonist SCH23390 during both training and testing
      might reveal a morphine place preference. Our results suggest that in previously
      drug-naive animals, D1 receptor antagonism during testing restores the opiate
      conditioned place preference that is normally absent when D1 receptors are
      blocked only during training, suggesting that BLA D1 receptors can mediate state
      dependent memory retrieval.

PMID- 23538065
TI  - Electrolytic lesion of the nucleus incertus retards extinction of auditory
      conditioned fear.
AB  - Fear memory circuits in the brain function to allow animals and humans to
      recognize putative sources of danger and adopt an appropriate behavioral
      response; and research on animal models of fear have helped reveal the anatomical
      and neurochemical nature of these circuits. The nucleus (n.) incertus in the
      dorsal pontine tegmentum provides a strong GABAergic projection to forebrain
      'fear centers' and is strongly activated by neurogenic stressors. In this study
      in adult male rats, we examined the effect of electrolytic lesions of n. incertus
      on different stages of the fear conditioning-extinction process and correlated
      the outcomes with anatomical data on the distribution of n. incertus-derived
      nerve fibers in areas implicated in fear circuits. In a contextual auditory fear
      conditioning paradigm, we compared freezing behavior in control (naive) rats
      (n=23) and rats with sham- or electrolytic lesions of n. incertus (n=13/group).
      The effectiveness and extent of the lesions was assessed post-mortem using
      immunohistochemical markers for n. incertus neurons-calretinin and relaxin-3.
      There were no differences between the three experimental groups in the
      habituation, acquisition, or context conditioning phases; but n. incertus
      lesioned rats displayed a markedly slower, 'delayed' extinction of conditioned
      freezing responses compared to sham-lesion and control rats, but no differences
      in retrieval of extinguished fear. These and earlier findings suggest that n.
      incertus-related circuits normally promote extinction through inhibitory
      projections to the amygdala, which is involved in acquisition of extinction
      memories.

PMID- 23538066
TI  - Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object
      recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.
AB  - Blonanserin is an atypical antipsychotic drug (APD) which, compared to other
      atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2
      antagonist. Comparing blonanserin with more broadly acting atypical APDs could be
      useful to test the contributions of actions at other monoamine receptors, e.g. 5
      HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR)
      deficit. In this study, we tested the effect of blonanserin alone, and in
      combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment
      with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2
      mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the
      PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished.
      Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5
      HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR
      deficit without diminishing activity during the acquisition or retention periods.
      The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1
      mg/kg), also diminished object exploration which prevented assessment of the
      effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating
      effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5
      HT1A receptors, but did not impair exploration. These results suggest that
      blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A
      receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP
      induced NOR deficit and provide a support for clinical trial of blonanserin in
      combination with tandospirone to ameliorate cognitive impairment in schizophrenia
      and to have fewer side effects.

PMID- 23538067
TI  - How bad was it? Differences in the time course of sensitivity to the magnitude of
      loss in problem gamblers and controls.
AB  - Previous research has shown that pathological gamblers show various cognitive
      distortions, especially in interpreting near losses. Using a modified blackjack
      task, we investigated the electrophysiological responses to near and full losses
      in problem gamblers and controls. We assessed the event-related brain potentials
      (ERPs) of 20 problem gamblers and 21 controls at two time points following
      negative game outcomes. We also studied the behavioral changes after near and
      full loss experiences. Between 270 and 320 ms following a loss, controls but not
      gamblers showed a differential ERP response to near and full losses suggesting
      that a near loss is evaluated more negatively than a full loss. However, between
      430 and 480 ms after a loss, the ERPs of both, gamblers and controls, showed a
      differential response as a function of the type of loss. Both groups became more
      cautious in their subsequent gambling behavior following near loss. The present
      study revealed differences in the time course of processing negative feedback in
      problem gamblers and normal controls, which might be due to gamblers
      preoccupation with gains rather than with losses.

PMID- 23538068
TI  - Transcranial direct current stimulation (tDCS) of Broca's area in chronic
      aphasia: a controlled outcome study.
AB  - BACKGROUND: In the last decade transcranial direct current stimulation (tDCS) has
      been introduced in aphasia post-stroke recovery as a tool for modulating
      neuroplasticity. However, it is still unclear whether tDCS should be applied at
      rest (off-line) or combined with behavioral treatment strategies (on-line),
      therefore, this study investigates the effect of repeated sessions of off-line
      tDCS on language recovery in post-stroke chronic aphasic patients. METHODOLOGY:
      Eight post-stroke patients with different type and degree of chronic aphasia
      underwent two weeks of off-line anodal tDCS (2 mA intensity for 20 min a day) on
      Broca's area and two weeks of sham stimulation as a control condition. Language
      recovery was measured assessing object and action naming abilities with a
      computerized picture naming task. RESULTS: No significant difference between
      anodal tDCS and sham stimulation, both for object and action naming tasks, was
      found. Descriptive analysis of single cases showed that after tDCS only one
      patient improved substantially on action naming task. CONCLUSION: With the
      exception of one patient, the overall results suggest that in chronic aphasic
      patients the off-line tDCS protocol applied in this study is not effective in
      improving noun and verb naming abilities.

PMID- 23538069
TI  - Repeated restraint stress enhances cue-elicited conditioned freezing and impairs
      acquisition of extinction in an age-dependent manner.
AB  - Affective disorders are believed to involve dysfunction within the amygdala, a
      key structure for processing emotional information. Chronic stress may contribute
      to affective disorders such as depression and anxiety via its effects on the
      amygdala. Previous research has shown that chronic stress increases amygdala
      neuronal activity in an age-dependent manner. However, whether these distinct
      changes in amgydala neuronal activity are accompanied by age-dependent changes in
      amygdala-dependent affective behavior is unclear. In this study, we investigated
      how chronic stress impacts amgydala-dependent auditory fear conditioning in
      adolescent and adult rats in a repeated restraint model. We found that repeated
      restraint enhanced conditioned freezing in both adolescent and adult rats. But
      repeated restraint led to impaired acquisition of fear extinction only in
      adolescent rats. Along with previous findings, these results suggest that chronic
      stress may precipitate affective disorders via differential mechanisms, with
      different outcomes at different ages.

PMID- 23538071
TI  - The unbearable lightheadedness of seizing: wilful submission to dissociative (non
      epileptic) seizures.

PMID- 23538070
TI  - Serum IgG levels in IV immunoglobulin treated chronic inflammatory demyelinating
      polyneuropathy.
AB  - OBJECTIVE: To determine the variability of serum IgG in patients with chronic
      inflammatory demyelinating polyneuropathy (CIDP). METHODS: All 25 CIDP patients
      had active but stable disease and were treated with individually optimised fixed
      dose IVIg regimens. IgG was measured by turbidimetry and variability was defined
      as coefficient of variation (CV). RESULTS: The intra-patient variability of the
      pre-treatment IgG levels, post-treatment levels and increase in serum IgG shortly
      after IVIg (DeltaIgG) was low (mean CV=3%, 4%, 10%). The inter-patient
      variability between patients treated with the same dose and interval was low in
      pre-treatment, post-treatment and DeltaIgG level (mean CV=13%, 11%, 20%). The
      DeltaIgG levels were associated with IVIg dosage (rs=0.78, p<0.001). CONCLUSIONS:
      Clinically stable CIDP patients show a steady-state in serum IgG after serial
      IVIg infusions. The low intra- and inter-patient variability in IgG may indicate
      that constant levels are required to reach this stability.

PMID- 23538072
TI  - Folate, vitamin B12, and S-adenosylmethionine.
AB  - Folate (vitamin B9) and cobalamin (vitamin B12) are essential for the normal
      development and function of the central nervous system. The metabolism of these
      vitamins is intimately linked and supports the synthesis of S-adenosylmethionine
      (SAMe), the major methyl group donor in methylation reactions. This article
      reviews the metabolic and clinical importance of folate, vitamin B12, and SAMe,
      as well as clinical trials in relation to depression and dementia.

PMID- 23538073
TI  - Omega-3 fatty acids in psychiatry.
AB  - Over the past 2 decades, omega-3 fatty acids (n-3FAs) have been increasingly used
      and studied in the United States and worldwide for various medical and
      psychiatric indications. Numerous published clinical trials have examined
      applications of different n-3FA preparations, primarily in mood disorders but
      also in psychotic disorders, attention-deficit disorder, obsessive-compulsive
      disorder, and personality disorders. Focusing on clinical issues, this article
      reviews the impact of n-3FAs on these conditions and covers the relevant
      research, side effects, dosage guidelines, and drug interactions; clinicians
      should thus be able to better advise patients who are already taking n-3FAs or
      are interested in trying them.

PMID- 23538074
TI  - Nutrients for prevention and treatment of mental health disorders.
AB  - The choice of nutrients for review is based on clinical evidence of efficacy in
      neuropsychiatric disorders and biochemical effects that are neuroprotective or
      reparative. Vitamins, minerals, amino acids, and metabolites have been shown to
      augment antidepressants, improve symptoms in anxiety disorders, depression,
      neurodegenerative diseases, brain injury, ADHD, and schizophrenia, and to reduce
      medication side effects. Detection and correction of vitamin and mineral
      deficiencies can be essential for recovery. Generally low in adverse effects when
      taken in therapeutic doses, nutrients can be combined for greater benefits.
      Further studies are warranted to validate these promising treatments.

PMID- 23538075
TI  - Phytomedicines for prevention and treatment of mental health disorders.
AB  - Herbal medicines supported by evidence of safety and efficacy in the treatment of
      anxiety, insomnia, fatigue, cognitive enhancement, mental focus, and sexual
      function are useful as monotherapies, multiherb combinations, and as adjuncts to
      prescription psychotropics. Relevant mechanisms of action and clinical guidelines
      for herbs in common use can assist clinicians who want to enhance treatment
      outcomes by integrating phytomedicinals into their treatment regimens. Research
      is needed to strengthen the evidence base and to expand the range of disorders
      that can be treated with herbal extracts. Studies of herbal genomic effects may
      lead to more targeted and effective treatments.

PMID- 23538076
TI  - Adaptogens in mental and behavioral disorders.
AB  - This article focuses on the most extensively studied adaptogens: Rhodiola rosea,
      Eleutherococcus senticosus, and Schisandra chinensis. Clinical studies, evidence
      for stress-protective and simulative effects, and molecular mechanisms of action
      on metabolic and other processes regulated by the neuroendocrine system are
      discussed.

PMID- 23538077
TI  - St. John's wort for the treatment of psychiatric disorders.
AB  - St. John's wort (Hypericum perforatum) has been extensively studied and reviewed
      for its use in depression; however, there is less salient discussion on its
      clinical application for a range of other psychiatric disorders. This article
      outlines the current evidence of the efficacy of St John's wort in common
      psychiatric disorders, including major depression, bipolar depression, attention
      deficit hyperactivity disorder, obsessive-compulsive disorder, social phobia, and
      somatization disorder. Mechanisms of action, including emerging pharmacogenetic
      data, safety, and clinical considerations are also detailed.

PMID- 23538078
TI  - Ginkgo biloba: indications, mechanisms, and safety.
AB  - Ginkgo biloba special extract (EGb761) is used in most randomized control trials.
      Indications include cognition and memory in Alzheimer disease, age-associated
      dementia, cerebral insufficiency, intermittent claudication, schizophrenia, and
      multi-infarct dementia. Dosages range from 80 to 720 mg/d for durations of 2
      weeks to 2 years. Mechanisms of action include increasing cerebral blood flow,
      antioxidant and antiinflammatory effects, with antiplatelet effects attributed to
      flavone and terpene lactones. Possible interactions with monoamine oxidase
      inhibitors, alprazolam, haloperidol, warfarin, and nifedipine have been reported.
      Optimal dosage/duration, dose-response characteristics, drug interactions,
      bioavailability, long-term effects, and optimal intervention timing should be the
      focus of future work.

PMID- 23538079
TI  - Saffron, passionflower, valerian and sage for mental health.
AB  - Many cultures have developed folk herbal remedies to treat symptoms of mental
      illness. An evidence-based view is now being developed for some of these so
      called alternative herbal treatments. This article discusses clinically relevant
      scientific information on medicinal extracts of 4 herbs: saffron, passionflower,
      valerian, and sage.

PMID- 23538080
TI  - Science of the mind: ancient yoga texts and modern studies.
AB  - The practice of yoga is gaining in popularity with a wide range of practices.
      Recent research and descriptions from the ancient texts are often concurrent with
      regard to the effects of the practice, taking into account expected differences
      between modern scientific terms and those used in the original texts. Voluntarily
      regulated yoga breathing practices form a bridge between physical and mental
      changes. The voluntarily regulated yoga breathing has distinct effects on
      metabolism, the autonomic nervous system, higher brain functions, and mental
      state. The effects of meditation on the nervous system and mental state are even
      clearer.

PMID- 23538082
TI  - Breathing practices for treatment of psychiatric and stress-related medical
      conditions.
AB  - Neurophysiological studies may explain how breathing techniques normalize stress
      response, emotion regulation, and autonomic and neuroendocrine system function.
      Breath practices have been shown to reduce symptoms of stress, anxiety, insomnia,
      post-traumatic stress disorder, mass disasters, depression, and attention deficit
      disorder. Technology-assisted breathing interventions facilitate therapeutic
      breathing by using either static cues such as a breath pacer or real-time
      feedback based on physiological parameters such as heart rate variability. The
      empirical literature indicates that technology-assisted breathing can be
      beneficial in mental health treatment, though it may not be appropriate for all
      individuals. Initial in-person training and evaluation can improve results.

PMID- 23538081
TI  - Tai Chi and Qigong for the treatment and prevention of mental disorders.
AB  - Tai Chi and Qigong are traditional Chinese exercises that are widely practiced
      for their health benefits and as martial arts. Evidence suggests that these
      practices may be effective at treating a range of physical health conditions, and
      at improving health-related quality of life. There is growing interest in the use
      of Tai Chi and Qigong to treat mental disorders, because they are noninvasive,
      exercise-based therapies, and because patients with mental disorders frequently
      use complementary and alternative medicine. Evidence is promising that these
      treatments may be effective in reducing depressive symptoms, stress, anxiety, and
      mood disturbances.

PMID- 23538083
TI  - Mindfulness meditation practices as adjunctive treatments for psychiatric
      disorders.
AB  - Mindfulness meditation-based therapies are being increasingly used as
      interventions for psychiatric disorders. Mindfulness-based stress reduction
      (MBSR) and mindfulness-based cognitive therapy (MBCT) have been studied
      extensively. MBSR is beneficial for general psychological health and pain
      management. MBCT is recommended as an adjunctive treatment for unipolar
      depression. Both MBSR and MBCT have efficacy for anxiety symptoms. Informed
      clinicians can do much to support their patients who are receiving mindfulness
      training. This review provides information needed by clinicians to help patients
      maximize the benefits of mindfulness training and develop an enduring meditation
      practice.

PMID- 23538084
TI  - Open focus attention training.
AB  - This article describes the role of attention training and brainwave synchrony
      training in the resolution of stress- and pain-related symptoms. It describes the
      origin of Open Focus attention training as it was distilled from observations of
      space-generated brain wave activity. It provides a map of the various attentional
      styles and associated EEG activity.

PMID- 23538085
TI  - Neurofeedback: an emerging technology for treating central nervous system
      dysregulation.
AB  - Neurofeedback is a machine-mediated noninvasive treatment modality based on the
      analysis and "feeding back" of electroencephalogram brainwaves, which has shown
      efficacy with a variety of central nervous system-based problems. It has special
      application where patients have adverse reaction to psychopharmacologic
      treatments and psychotherapy, cognitive behavioral therapy, and dialectical
      behavior therapy have proved ineffective. Treatment modalities include active
      forms based on operant conditioning, involving a subject's response to stimuli.
      Neurofeedback is strong in clinical confirmations of efficacy (case studies) and
      has thus far limited controlled studies in the peer-reviewed journals.

PMID- 23538086
TI  - Cranial electrotherapy stimulation for treatment of anxiety, depression, and
      insomnia.
AB  - Cranial electrotherapy stimulation is a prescriptive medical device that delivers
      a mild form of electrical stimulation to the brain for the treatment of anxiety,
      depression, and insomnia. It is supported by more than 40 years of research
      demonstrating its effectiveness in several mechanistic studies and greater than
      100 clinical studies. Adverse effects are rare (<1%), mild, and self-limiting,
      consisting mainly of skin irritation under the electrodes and headaches. Often
      used as a stand-alone therapy, because results are usually seen from the first
      treatment, cranial electrotherapy stimulation may also be used as an adjunctive
      therapy.

PMID- 23538087
TI  - Testosterone and mood in aging men.
AB  - Age-associated hypothalamic-pituitary-gonadal (HPG) axis hypofunction, or partial
      androgen deficiency of the aging male, is thought to be responsible for various
      age-associated conditions such as reduced muscle and bone mass, mobility
      limitations, frailty, obesity, sleep apnea, cognitive impairment, sexual
      dysfunction, and depression. It has been difficult to establish consistent
      correlations between these symptoms and plasma testosterone levels in middle-aged
      men, but testosterone replacement does lead to improved muscle strength, bone
      density, and sexual function. This article focuses on the relationship between
      testosterone and mood in older men, and the treatment of age-related depression
      with exogenous testosterone.

PMID- 23538088
TI  - Perinatal depression and anxiety: beyond psychopharmacology.
AB  - A discussion of pharmacologic and nonpharmacologic management of mental disorders
      in the pregnant woman is presented, with the focus on alternative health
      approaches and nutrition awareness. The article explores some considerations of
      modifiable risk factors thought to play a role in epigenetic manifestations of
      infant and child illness. Several case examples show the potential for
      integrative medicine in patients of reproductive age.

PMID- 23538089
TI  - Along roads less traveled: complementary, alternative, and integrative
      treatments.

PMID- 23538090
TI  - Reductive degradation of oxygenated polycyclic aromatic hydrocarbons using an
      activated magnesium/co-solvent system.
AB  - This study evaluates the capability of zero-valent magnesium and a protic co
      solvent to promote the degradation of oxygenated polycyclic aromatic hydrocarbons
      compounds, specifically 9-fluorenone, 9,10-anthraquinone, 7,12
      benz(a)anthraquionone, and 7H-benz(de)anthracene-7-one. At room temperature
      conditions, greater than 86% degradation efficiency is observed after 24h of
      reaction time for a mixture containing 0.05 g of magnesium and four selected
      oxygenated aromatic hydrocarbons with 250 mg L(-1) concentrations. It is noted
      that glacial acetic acid is needed as an activator for the degradation reaction
      to proceed. It is also presumed that the acid removes oxide and hydroxide species
      from the magnesium surface. With the GC-MS analysis of the reaction products,
      possible reductive pathways are suggested. Furthermore, this study is the first
      report on the degradation of these emerging contaminants and it is proposed that
      the magnesium-powder/protic-solvent system is a promising low-cost reagent and
      may allow for the future development of an economic and environmentally-friendly
      remediation application.

PMID- 23538091
TI  - Impact of dissolved silica on arsenite removal by nano-particulate FeS and FeS
      coated sand.
AB  - This work evaluated the inhibitory effect of dissolved silica on arsenite
      adsorption to nanoparticulate FeS (NP-FeS) or mackinawite and FeS-coated sand (CS
      FeS) sorbents. Arsenite retention by the NP-FeS solid was not affected by
      dissolved silicate over a wide range in pH, in contrast to the known inhibitory
      effect of dissolved silica on As(III) uptake by Fe-(hydr)oxide systems. However,
      some inhibition was observed in CS-FeS system at pH 9. This latter result is
      attributed to the co-existence of both FeS and small amounts of Fe-(hydr)oxide
      phases on the sand surface. Given the ubiquitous presence of dissolved Si in
      groundwater, FeS-based sorbents may have an advantage for As retention compared
      to those based on Fe-(hydr)oxides in reducing subsurface environments.

PMID- 23538092
TI  - Evaluation of lead concentration by one-box type multimedia model in Lake Biwa
      Yodo River basin of Japan.
AB  - A one box type multimedia model was developed and applied for Lake Biwa-Yodo
      River basin in Japan to assess the distribution of lead in the environment. This
      model is based on mass balance and includes four environmental media; the
      atmosphere, the soil, the water body, and the sediment. The mass balance of lead
      is represented by the summation of mass transfer flux at equilibrium, emission
      flux, advection flux, and deposition flux or sedimentation flux. In the case of
      metallic compounds, dissolution rate and exchange equilibrium have also been
      taken into consideration. Pollutant Release and Transfer Registry (PRTR) in Japan
      was used as one of the major data source for this study. The emission of lead in
      Lake Biwa-Yodo River basin is calculated based on five sources of registered
      emission in PRTR, unregistered emission in PRTR, incinerators, leaded gasoline,
      and landfills. In this study, we estimated lead emission from 1957 to 2007 to
      observe the temporal accumulation of lead. Calculated lead concentrations were
      compared with the measured/observed concentrations. It was found out that the
      model could closely predict lead concentration in the soil and the water body.
      The concentration in the atmosphere was underestimated by the calculated
      concentrations. The reason was attributed to the underestimation of the amount of
      lead emission from incinerators.

PMID- 23538093
TI  - Prognostic value of cerebral injury following transfemoral aortic valve
      implantation.
AB  - AIMS: To evaluate the impact of serological, imaging and clinical measures of
      cerebral injury on patient self-sufficiency and survival after transcatheter
      aortic valve implantation (TAVI). METHODS AND RESULTS: Before and three days
      after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic
      resonance imaging (DW-MRI) and neurological performance utilising National
      Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was
      determined with established score systems (instrumental activities of daily
      living score, Barthel Index). Parameters of cerebral injury were investigated for
      their impact on self-sufficiency and all-cause mortality after 30 days and one
      year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4+/-18.1, STS
      score: 7.9+/-5.7), of whom 39 completed the imaging protocol. The incidences of
      NSE increase, new embolic events in DW-MRI, and neurological deficit early after
      TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant
      comorbidities, reflected by higher risk scores, had significant impact on
      outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to
      self-sufficiency nor to survival one year after TAVI. CONCLUSIONS: In this
      observational pilot study, "silent" cerebral injury is neither related to
      dependent lifestyle nor to mortality during the first year after TAVI. However,
      long-term follow-up is needed to elucidate fully the impact of silent stroke.
      Clinical trials number: NCT00883285.

PMID- 23538094
TI  - Free radicals generated by tantalum implants antagonize the cytotoxic effect of
      doxorubicin.
AB  - Little is known about the interaction between antineoplastic drugs and implants
      in bone cancer patients. We investigated the interaction between commercially
      available porous tantalum (Ta) implants and the chemotherapeutic drug,
      Doxorubicin (DOX). DOX solutions were prepared in the presence of Ta implant. The
      changes in fluorescence intensity of the DOX chromophore were measured by
      spectrofluorometry and the efficacy of DOX was evaluated by viability of rabbit
      rectal tumor cells (VX2). After 5 min interaction of the DOX solution (5 MUg/ml)
      with the Ta implant, the fluorescent intensity of the DOX solution was 85%
      degraded, and only 20% the drug efficacy to kill VX2 cells was retained. However,
      after adding a reducing agent, Dithiothreitol (DTT, 10 MUg/ml), 80% of the
      original fluorescence and 50% of the drug efficacy were restored while UV
      irradiation enhanced drug degradation in the presence of Ta implant. The action
      of DTT and UV irradiation indicated that reactive oxygen species (ROS) were
      involved in the drug degradation mechanism. We detected that Ta implants in
      aqueous medium produced hydroxyl radicals. Cells showed higher intracellular ROS
      activity when culture medium was incubated with the Ta implant prior to cell
      culture. It is concluded that the porous Ta implant antagonizes the cytotoxicity
      of DOX via ROS generation of the porous Ta implant.

PMID- 23538095
TI  - Enhanced uptake and cytotoxity of folate-conjugated mitoxantrone-loaded micelles
      via receptor up-regulation by dexamethasone.
AB  - Folate conjugated amphiphilic polymeric micelles have attracted much attention
      for active targeted delivery of drugs in folate receptor alpha (FR-alpha)
      positive tumors. However, the efficacy improvement of targeted delivery folate
      based nanovehicles was limited by the abundance of FR-alpha on the surface of
      tumor cells. Recently, it was found that FR-alpha expression of Hela cells could
      be up-regulated by modulators such as dexamethasone, which open a new avenue to
      enhance the efficiency of targeted delivery from the biological view. In this
      study, folate-conjugated or plain lipid-core micelles loaded with fluorescent
      coumarin 6 or mitoxantrone (MTN) were prepared by self-assembly. In addition,
      FOLR1 mRNA and cell surface FR-alpha levels were evaluated in Hela cells with
      dexamethasone treatment. The endocytosis of folate-conjugated or plain micelles
      loaded with coumarin 6 was examined with confocal microscopy and flow cytometry,
      which displayed that folate-conjugated micelles can be internalized more
      efficiently in dexamethasone-treated Hela cells than in normal Hela cells.
      Moreover, the antitumor activity of folate-conjugated micellar MTN was also
      improved through up-regulation of FR-alpha. Therefore, FR-alpha up-regulation
      using modulators has great potential to improve the therapeutic efficacy of
      folate-conjugated nanovehicles in some FR-alpha positive tumors via receptor
      mediated endocytosis.

PMID- 23538096
TI  - Development of an ex vivo retention model simulating bioadhesion in the oral
      cavity using human saliva and physiologically relevant irrigation media.
AB  - In recent years, there has been a particular interest in bioadhesive formulations
      for oromucosal drug delivery as this may promote prolonged local therapy and
      enhanced systemic effect. Saliva plays a vital role in oromucosal drug absorption
      by dissolving the drug and presenting it to the mucosal surface. However, the
      rheological, chemical, and interfacial properties of this complex biological
      fluid may strongly affect the adhesion of bioadhesive formulations. There is a
      need for well characterized in vitro models to assess the bioadhesive properties
      of oral dosage forms for administration in the oral cavity. Thus we aimed at
      developing an advanced ex vivo buccal retention model, with focus on choosing a
      physiologically relevant irrigation media closely resembling human saliva. Spray
      dried chitosan microparticles containing metformin hydrochloride as an example of
      a small hydrophilic drug, were employed as bioadhesive formulations. Chewing
      stimulated human whole saliva was collected and characterized for use in
      retention studies in comparison with four artificial irrigation media; phosphate
      buffer, Saliva Orthana((r)), porcine gastric mucin base media (PGM3), and xanthan
      gum based media (XG2). Retention of metformin, applied as spray dried
      microparticles on porcine buccal mucosa, greatly depended on the characteristics
      of the irrigation media. When rheology of the irrigation media was examined,
      changes in retention profiles could be interpreted, as irrigation media
      containing mucin and xanthan gum possessed a higher viscosity than phosphate
      buffer, which led to longer retention of the drug due to better hydration of the
      mucosa and the spray dried microparticles. Metformin retention profiles were
      comparable when human saliva, Saliva Orthana((r)), or PGM3 were used as
      irrigation media. Moreover, PGM3 displayed physico-chemical properties closest to
      those of human saliva with regard to pH, protein content and surface tension.
      Saliva Orthana((r)) and PGM3 are therefore considered as suitable irrigation
      media for further retention studies.

PMID- 23538097
TI  - On the nanotoxicity of PAMAM dendrimers: Superfect(r) stimulates the EGFR-ERK1/2
      signal transduction pathway via an oxidative stress-dependent mechanism in HEK
      293 cells.
AB  - Polyamidoamine (PAMAM) dendrimers are cationic branch-like macromolecules that
      may serve as drug delivery systems for gene-based therapies such as RNA
      interference. For their safe use in the clinic, they should ideally only enhance
      drug delivery to target tissues and exhibit no adverse effects. However, little
      is known about their toxicological profiles in terms of their interactions with
      cellular signal transduction pathways such as the epidermal growth factor
      receptor (EGFR). The EGFR is an important signaling cascade that regulates cell
      growth, differentiation, migration, survival and apoptosis. Here, we investigated
      the impact of naked, unmodified Superfect (SF), a commercially available
      generation 6 PAMAM dendrimer, on the epidermal growth factor receptor (EGFR)
      tyrosine kinase-extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway in
      human embryonic kidney (HEK 293) cells. At concentrations routinely used for
      transfection, SF exhibited time and dose-dependent stimulation of EGFR and ERK1/2
      phosphorylation whereas AG1478, a selective EGFR tyrosine kinase antagonist,
      inhibited EGFR-ERK1/2 signaling. SF-induced phosphorylation of EGFR for 1h was
      partly reversible upon removal of the dendrimer and examination of cells 24
      later. Co-treatment of SF with epidermal growth factor (EGF) ligand resulted in
      greater EGFR stimulation than either agent alone implying that the stimulatory
      effects of SF and the ligand are synergistic. Dendrimer-induced stimulation of
      EGFR-ERK1/2 signaling could be attenuated by the antioxidants apocynin, catalase
      and tempol implying that an oxidative stress dependent mechanism was involved.
      These results show for the first time that PAMAM dendrimers, aside from their
      ability to improve drug delivery, can modulate the important EGFR-ERK1/2 cellular
      signal transduction pathway - a novel finding that may have a bearing on their
      safe application as drug delivery systems.

PMID- 23538099
TI  - [Giant schwannoma of musculocutaneous nerve (a case report)].
AB  - Schwannoma is a tumor that develops from nerve sheath. The authors report an
      original observation of a giant schwannoma developed in the arm depending on the
      musculocutaneous nerve. The diagnosis was based on MRI appearance. Confirmation
      of the diagnosis was made by histological examination. Surgical treatment was
      resection, taking care preserving adjacent nerve fibers. This allowed recovery
      without any sequela. Recurrence rate and potential for malignant transformation
      of this type of tumor is low. 

PMID- 23538098
TI  - Oligoarginine-modified biodegradable nanoparticles improve the intestinal
      absorption of insulin.
AB  - The strategy of oral administration of bioactive macromolecules using cell
      penetrating peptides (CPPs) is restricted to covalent linkage or electrostatic
      interaction between the cargo and CPPs. In the present study, we devised an
      approach utilizing CPP-functionalized poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles as a carrier for oral delivery of insulin. Pegylated PLGA
      nanoparticles were modified with poly(arginine)8 enantiomers (l-R8 and d-R8) via
      a maleimide-mediated covalent conjugating procedure. The physical and chemical
      features of the nanoparticles were characterized, which confirmed the successful
      immobilization of R8 to the nanoparticles. Using a Caco-2 cell monolayer model,
      R8-modified nanoparticles were found to exhibit significantly increased cellular
      uptake and transportation. Pharmacokinetics and pharmacodynamics of the insulin
      loaded nanoparticles were evaluated with rats by intestinal administration.
      Compared to the unmodified nanoparticles, l-R8 and d-R8 modified-nanoparticles
      increased the relative bioavailabilities of insulin by 3.2- and 4.4-times,
      meanwhile, improved the hypoglycemic effects by 2.5- and 3.7-times, respectively.
      Neither of the R8-modified nanoparticles caused perceptible histological
      toxicities. The results implied that surface modification of biodegradable
      nanoparticles with poly(arginine)8, especially with the d-form enantiomer, showed
      remarkable advancement in promoting the intestinal absorption of insulin. This
      delivery system is also promising for the delivery of a wide variety of bioactive
      macromolecules by oral administration.

PMID- 23538100
TI  - [Adamantinoma of the clavicle: rare tumor for rare location].
AB  - Adamantinoma is a rare primary low-grade malignant tumor composed of cells with
      epithelial and fibrous characteristics. It represents 0.4% of all primitive
      malignant bone tumours. It is predominantly located in the mid-shaft of tibia. We
      report an adamantinoma of the clavicle, occurring in a 19-year-old female
      patient. The lateral half of the clavicle was excised. After a period of 3 years,
      she is still remaining free of local recurrence and metastatic disease. 

PMID- 23538101
TI  - [Interest and feasibility of local anesthesia in the management of massive
      extravasation of contrast medium].
AB  - Radiographic contrast medium extravasation in the upper extremity is not rare. It
      can be responsible for functional (compartment syndrome) and cosmetic sequelae.
      It is very difficult to predict the degree of final tissue injury in emergency.
      Currently, there is no consensus of emergency treatment. However, liposuction and
      saline washout as described by Gault is the usual treatment. We report the case
      of 42 year-old woman with radiographic contrast medium extravasation in the arm
      (120 cm(3)) with neurologic complications involving median nerve and medial
      cutaneous nerves of arm and forearm. Emergency conservative surgical washout with
      saline solution was performed under local anaesthesia. Drainage was realised by
      lipoaspiration cannula and arm massages. Clinical and radiological results were
      estimated. Ultimately, the patient has retained no sequela. Contrast medium
      extravasation in the arm with tissue complications is exceptional. We think that
      saline washout and lipoaspiration cannula drainage are an emergency useful
      treatment for radiographic contrast medium extravasation with tissue
      complications. Tolerance of the management was quite good. Postoperative X-rays
      are useful to assess treatment efficacy.

PMID- 23538102
TI  - [Management of infection risk in asplenic patients].
AB  - Each year in France 6000 to 9000 patients are splenectomised or spleen embolized.
      As spleen has immunological functions, it contributes to protect against
      infections. Thus, hypo or asplenia increase the risk of infection, especially the
      risk of Overwhelming Post-Splenectomy Infection (OPSI). OPSI is a medical
      emergency, characterized by aspecific symptoms, which may rapidly progress to
      fulminant infection and death in 50% of cases within 48 h. Encapsulated bacteria
      as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis
      are most of the time responsible of these infections in asplenic patients. To
      prevent OPSI, several measures are essential and must begin before a scheduled
      surgery or just after an urgent splenectomy. Patients must carry a card. The
      first proposed prevention measure is to enhance partial surgery when it's
      possible. Then, the two other measures, antibiotic prophylaxis and vaccination,
      shall be implemented whatever is the indication of surgery. Postoperative
      antibiotic prophylaxis by phenoxymethyl-penicillin is prescribed for two years
      minimum and lifelong prophylaxis should be offered to high risk of pneumococcal
      infection patients. Pneumococcal, H. influenzae type b and meningococcal
      vaccination should be administered 2 to 6 weeks before scheduled splenectomy and
      2 weeks after urgent surgery. Yearly, patients must receive Influenza
      vaccination. As an interindividual variation exists in vaccinal response,
      measurement of serotype-specific antibodies can be used, if available, to
      individualized risk patients and to organize revaccination. Finally, to prevent
      OPSI, patient and next-of-kin must be educated about prevention measures and
      infectious risk to optimize patient's compliance.

PMID- 23538103
TI  - [Guidelines for regional anesthetic and analgesic techniques in the treatment of
      chronic pain syndromes].

PMID- 23538104
TI  - Barriers and solutions for timely initiation of antenatal care in Kigali, Rwanda:
      health facility professionals' perspective.
AB  - OBJECTIVE: timely initiation of antenatal care (i.e. within the first trimester)
      is associated with attendance of the full recommended regimen of antenatal
      visits. This study assessed social and behavioural factors that affect timely
      initiation of antenatal care in Kigali, Rwanda from the perspective of health
      facility professionals. DESIGN: health facility professionals involved in
      antenatal care provision were interviewed on their perceptions about untimely
      initiation of antenatal care based on open-ended questions. These one-on-one
      interviews were tape recorded and transcribed for analysis. SETTING: interviews
      were performed in June and July 2011 at Muhima Health Center in Kigali, Rwanda.
      PARTICIPANTS: 17 health facility professionals with a wide range of skills and
      experience levels were selected from the 36 total staff members of Muhima Health
      Center based on their participation in and knowledge of antenatal care.
      MEASUREMENTS AND FINDINGS: inductive content analysis was used to group responses
      from these qualitative interviews with the goal of creating a conceptual map
      around barriers and solutions for untimely antenatal care. Qualitative responses
      were coded to identify the most common themes and sub-themes following a
      consensus methodology. The health-care professional interviews identified five
      themes as barriers to timely initiation of antenatal care: (1) lack of knowledge;
      (2) experience with previous births; (3) issues with male partners not
      willing/able to attend the clinic; (4) poverty or problems with health insurance;
      and (5) antenatal care culture. As potential solutions to these hurdles, the
      following themes were identified: (1) maternal/community education and
      sensitisation; (2) incentives to attend antenatal care visits; and (3) tracking
      the content and recommended number of antenatal visits. KEY CONCLUSIONS:
      qualitative results indicate that behavioural contextual interventions may help
      overcome antenatal care barriers. The Rwandan Government and health facilities
      should work together with target communities to improve antenatal care
      compliance, taking into account the solutions suggested by the health facility
      professional interviews. IMPLICATIONS FOR PRACTICE: study findings suggest that
      there are specific solutions to increase adherence with timely initiation of
      antenatal care in Rwanda, including education and sensitisation, modifying
      couples' HIV testing policies, addressing costs of antenatal care, and tracking
      the number of recommended antenatal visits.

PMID- 23538105
TI  - [Pregnancies among underage girls in Guadeloupe: a new inventory].
AB  - OBJECTIVES: In Guadeloupe (French West Indies), fecondity rate of teenagers is
      higher than in mainland France. The aim of our study was to analyze
      sociodemographic characteristics and perinatal indicators among underage girls
      and to compare them to those of a previous study also conducted in our maternity
      unit in 1993 and 1994. MATERIALS AND METHODS: The sociodemographic, medical,
      obstetrical and neonatal data of 163 underage pregnant girls delivered from 2009
      to 2010 at the University hospital of Pointe-a-Pitre/Abymes were collected
      retrospectively and compared with the previous study. RESULTS: In 16 years, in
      contrast to perinatal indicators, which did not significantly evolve, the
      sociodemographic characteristics of this population have changed. In addition,
      the increase of neonatal morbidity seems to be related to late initiation of
      obstetrical care, which also still remains insufficient. CONCLUSION: Our results
      are close to those described in the other French regions and have hardly evolved
      since our previous study. The differences found for the obstetric and perinatal
      risks seem to be related to sociodemographic factors surrounding these underage
      pregnancies. Those factors should be taken into consideration in any approach
      aiming to reduce incidence and prevent complications of pregnancies among
      teenagers.

PMID- 23538106
TI  - [Analysis of fetal heart rate abnormalities occurring within one hour after
      laying of epidural analgesia].
AB  - OBJECTIVES: The objective of this study is to classify abnormalities of fetal
      heart rate (FHR) occurring in the first hour after performing the epidural
      analgesia, and to assess the impact of these abnormalities on delivery and on
      after-birth neonatal state. PATIENTS AND METHODS: Retrospective study of 6676
      patients continuously from 1 January 2007 to 31 December 2010 who benefited,
      during the labor, of epidural analgesia. Seven hundred and sixty (14,1%)
      presented anomalies of FHR in the hour following the laying of epidural (group
      1), and 5916 showed no abnormalities of the RCF (group 2). RESULTS: Among the 760
      anomalies of the FHR in the hour following the laying of epidural, 319 (42%)
      showed prolonged decelerations, 169 (22.2%) variable decelerations, 122 (16.1%)
      early decelerations, 110 (14.5%) late decelerations and 40 bradycardia (5.3%). In
      the group 1, incidence of caesarean delivery was 21.4% (163 patients); in group
      2, it was 9.63% (P<0.002). In group 1, the umbilical artery pH was less than 7.20
      in 13,6% of patients, whereas in group 2, the prevalence was only 6,5% (P<0.002).
      There is no statistically significant differences on Apgar score between the two
      groups. CONCLUSION: This study helped to characterize anomalies in the FHR
      following epidural. There is an increase of obstetric interventions. There is no
      impact on neonatal clinical state. The administration of systematic ephedrine
      shall be investigated to reduce these interventions.

PMID- 23538107
TI  - Occurrence and fate of eleven classes of antibiotics in two typical wastewater
      treatment plants in South China.
AB  - Wastewater treatment plants (WWTPs) are regarded as one of the most important
      sources of antibiotics in the environment. Two sampling campaigns over a period
      of one year in two wastewater treatment plants (plant A: activated sludge with
      chlorination, and plant B: oxidation ditch with UV) of Guangdong Province, China
      were carried out to assess the occurrence and fate of 11 classes of 50
      antibiotics. The wastewater samples were extracted by Oasis HLB cartridges (6mL,
      500 mg), while the solid samples (sludge and suspended solid matter) were
      extracted by ultrasonic-assisted extraction with solvents (acetonitrile and
      citric acid buffer), followed by an enrichment and clean-up step with solid-phase
      extraction using SAX-HLB cartridges in tandem. The results showed the presence of
      20 and 17 target compounds in the influents and effluents, respectively, at the
      concentrations ranging from low ng/L to a few MUg/L. Sulfamethoxazole,
      norfloxacin, ofloxacin, anhydro erythromycin and trimethoprim were most
      frequently detected in the WWTPs wastewaters. Twenty-one antibiotics were found
      in the sewage sludge from the two WWTPs at the concentrations up to 5800ng/g,
      with tetracycline, oxytetracycline, norfloxacin and ofloxacin being the
      predominant antibiotics. The total mass loads of antibiotics per capita in the
      two plants ranged from 494 to 901 MUg/d/inhabitant (672+/-182 MUg/d/inhabitant)
      in the influents, from 130 to 238 MUg/d/inhabitant (175+/-45 MUg/d/inhabitant) in
      the effluents and from 107 to 307 MUg/d/inhabitant (191+/-87.9 MUg/d/inhabitant)
      in the dewatered sludge, respectively. The aqueous removals for sulfonamides,
      macrolides, trimethoprim, lincomycin and chloramphenicol in the WWTPs were mainly
      attributed to the degradation processes, while those for tetracyclines and
      fluoroquinolones were mainly due to the adsorption onto sludge.

PMID- 23538108
TI  - Analysis of the effect of meteorological factors on dewfall.
AB  - To get an insight into when dewfall will occur and how much to expect we carried
      out extensive calculations with the energy balance equation for a crop surface to
      1) identify the meteorological factors which determine dewfall, 2) establish the
      relationship between dewfall and each of them, and 3) analyse how these
      relationships are influenced by changes in these factors. The meteorological
      factors which determine dewfall were found to be air temperature (T(a)), cloud
      cover (N), wind speed (u), soil heat flux (G), and relative humidity (h(r)). Net
      radiation is also a relevant factor. We did not consider it explicitly, but
      indirectly through the effect of temperature on the night-time radiation balance.
      The temperature of the surface (T(s)) where dew forms on is also important.
      However, it is not a meteorological factor, but determined by the aforementioned
      parameters. All other conditions being equal our study revealed that dewfall
      increases linearly with decreasing N or G, and with increasing h(r). The effect
      of T(a) and u on dewfall is non-linear: dewfall initially increases with
      increasing T(a) or u, and then decreases. All five meteorological factors can
      lead to variations in dewfall between 0 and 25 W m(-2) over the range of their
      values we studied. The magnitude of the variation due to one factor depends on
      the value of the others. Dewfall is highest at N=0, G=0, and h(r)=1. Ta at which
      dewfall is highest depends on u and vice versa. The change in dewfall for a unit
      change in N, G or h(r) is not affected by the value of N, G or h(r), but
      increases as T(a) or u increase. The change in dewfall for a unit change in Ta or
      u depends on the value of the other four meteorological factors.

PMID- 23538109
TI  - Impact of dry weather discharges on annual pollution from a separate storm sewer
      in Toulouse, France.
AB  - The city of Toulouse with its separate sewer system is ideal for studying
      stormwater. However, during dry weather, the storm sewer also discharges water
      into the environment, and it is the impact of these discharges on annual
      pollution from storm sewer that is the object of this study. Samples have been
      taken from the outlets of two storm drains located in heavily and moderately
      urbanized areas. Sampling has been undertaken during wet weather and during dry
      weather between January 2010 and February 2011. Three dry weather and two wet
      weather samples have been taken every three months and from each outlet. The
      overall pollution parameters have been analyzed (chemical oxygen demand,
      biological oxygen demand, total nitrogen, ammonium, nitrate, total phosphorus,
      suspended solid matter, volatile suspended matter, pH, conductivity, turbidity).
      Characterization has been completed by analysis of trace organic compounds:
      polycyclic aromatic hydrocarbons, total hydrocarbons, methyl tert-butyl ether,
      diethylhexylphthalate, nonylphenols, hormones (estradiol, ethinylestradiol). For
      certain parameters, the results obtained did not conform to legislative
      requirements concerning discharge into the natural environment. Correlations
      between these parameters have been studied, and identified between several of
      them using principal component analysis. The most important correlation observed
      was between conductivity and concentration in total phosphorus for one of the
      outlet. Results showed that dry weather had an impact on annual pollution load
      from separate storm sewer and that level of urbanization was also a factor. The
      effect of season has been studied but no significant impact was found.

PMID- 23538110
TI  - Knowledge and prevention of tick-borne diseases vary across an urban-to-rural
      human land-use gradient.
AB  - We sought to determine the behavioral risk of exposure to tick-borne diseases
      across a human land-use gradient in a region endemic for diseases transmitted by
      the lone star tick. We measured the knowledge, attitudes, and preventive
      behaviors of visitors to 14 suburban, exurban, and rural recreational parks. A
      structured interview was conducted to determine respondents' (n=238) knowledge of
      tick-borne disease risk, perceived susceptibility to tick-borne disease, and tick
      bite prevention behaviors. We found significant differences across park types for
      most personal protective behaviors. Individuals in exurban parks were more likely
      to perform frequent tick checks and use chemical insect repellents compared to
      other park types (p<0.001), while suburban park visitors were more likely to
      avoid tick habitats (p<0.05). Disparities exist in the level of knowledge,
      perceived personal risk, and use of preventive measures across the human land-use
      gradient, suggesting that targeted public health intervention programs could
      reduce behavioral exposure risk by addressing specific gaps in knowledge and
      prevention.

PMID- 23538111
TI  - Molecular survey of hard ticks in endemic areas of tick-borne diseases in China.
AB  - Over the past several years, there was a substantial increase in the number of
      cases of known and novel tick-borne infections in humans in China. To better
      understand the ticks associated with these infections, we collected hard ticks
      from animals or around livestock shelters in 29 localities in 5 provinces
      (Beijing, Henan, Hubei, Inner Mongolia, and Zhejiang) where cases of tick-borne
      illness were reported. We collected 2950 hard ticks representing 7 species of 4
      genera (Dermacentor sinicus, Haemaphysalis flava, Haemaphysalis longicornis,
      Ixodes granulatus, Ixodes persulcatus, Rhipicephalus microplus, and Rhipicephalus
      sanguineus). These ticks were identified to species using morphological
      characters initially. We then sequenced the mitochondrial small subunit rRNA (12S
      rRNA) gene, cytochrome oxidase subunit 1 (COI) gene, and the second internal
      transcribed spacer (ITS2) gene of these ticks, and conducted phylogenetic
      analyses. Our analyses showed that the molecular and morphological data are
      consistent in the identification of the 7 tick species. Furthermore, all these 7
      tick species from China were genetically closely related to the same species or
      related species found outside China. Rapid and accurate identification and long
      term monitoring of these ticks will be of significance to the prevention and
      control of tick-borne diseases in China.

PMID- 23538112
TI  - Detection and quantification of acute myocardial ischemia by morphologic
      evaluation of QRS changes by an angle-based method.
AB  - OBJECTIVE: In acute myocardial ischemia changes within the QRS complex can add
      valuable information to that from the repolarization phase. This study evaluates
      three angles obtained from the main slopes of the R-wave within the QRS complex
      to assess acute myocardial ischemia. METHODS: The QRS angles, denoted by OR (R
      wave angle), OU (up-stroke angle) and OD (down-stroke angle), were evaluated in
      12-lead electrocardiogram (ECG) recordings of 79 patients before and during
      coronary occlusion by elective percutaneous coronary intervention (PCI). In a
      subset of 38 patients, ischemia was quantified by myocardial scintigraphy.
      RESULTS: At baseline the QRS angles presented low variations. During occlusion,
      OU and OD developed a fast and abrupt change, whereas OR showed a smaller and
      gradual change. There were significant correlations between both maximal and sum
      of positive change in OR and ischemia: r=0.67; p<0.001 and r=0.78; p<0.001, for
      extent, and r=0.60; p<0.001 and r=0.73; p<0.001, for severity, respectively.
      Prediction of extent and severity of ischemia increased by 50% by adding OR
      changes to ST-segment changes, for LCX occlusions, whereas increased by 12.1% and
      24.6% for LAD and RCA occlusions, respectively. No significant correlation was
      seen between OU and OD angles and ischemia. CONCLUSIONS: Evaluation of QRS angles
      from the standard 12-lead ECG represents a sensitive marker for detection of
      acute myocardial ischemia, whereas, OR changes can be used for prediction of its
      extent and severity.

PMID- 23538113
TI  - Allogeneic hematopoietic cell transplantation from unrelated donors in multiple
      myeloma: study from the Italian Bone Marrow Donor Registry.
AB  - To evaluate trends in allografting from unrelated donors, we conducted a study on
      196 consecutive myeloma patients transplanted between 2000 and 2009 in Italy.
      Twenty-eight percent, 37%, and 35%, respectively, received myeloablative, reduced
      intensity, and nonmyeloablative conditioning. In these 3 cohorts, 1-year and 5
      year transplantation-related mortalities were 28.8% and 37.0%, 20.3% and 31.3%,
      and 25.0% and 30.3%, respectively (P = .745). Median overall survival (OS) and
      event-free survival from transplantation for the 3 cohorts were 29 and 10 months,
      11 and 6 months, and 32 and 13 months, respectively (P = .039 and P = .049).
      Overall cumulative incidences of acute and chronic graft-versus-host-disease
      (GVHD) were 46.1% and 51.1%. By Cox multivariate analyses, chronic GVHD was
      significantly associated with longer OS (hazard ratio [HR], .51; P = .009),
      whereas the use of peripheral blood stem cells was borderline significant (HR,
      .55; P = .051). Better response posttransplantation was associated with longer
      event-free survival (HR, 2.13 to 4.25; P < .001). Acute GVHD was associated with
      poorer OS (HR, 2.53; P = .001). This analysis showed a strong association of
      acute and chronic GVHD and depth of response posttransplantation with clinical
      outcomes. Long-term disease control remains challenging regardless of the
      conditioning. In the light of these results, prospective trials may be designed
      to better define the role of allografting from unrelated donors in myeloma.

PMID- 23538114
TI  - Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs
      implicated by a viral entry blocking mechanism.
AB  - A series of chiral gossypol derivatives and its analogs were synthesized and
      tested in vitro for their anti-H5N1 activity. Interestingly, (+)-gossypol
      derivatives and its analogs were more active against H5N1 than the corresponding
      (-)-gossypol derivatives and its analogs. Through a simple chemical modification
      with amino acids, less active chiral gossypol could be converted into more active
      derivatives, and most of chiral gossypol derivatives were more potent against
      H5N1 than 1-adamantylamine. With regard to the mechanism of action, chiral
      gossypol derivatives and its analogs might impair the virus entry step of cell
      infection, likely targeting to HA2 protein.

PMID- 23538117
TI  - National Healthcare Safety Network report, data summary for 2011, device
      associated module.

PMID- 23538115
TI  - Discovery of adamantane based highly potent HDAC inhibitors.
AB  - Herein, we report the development of highly potent HDAC inhibitors for the
      treatment of cancer. A series of adamantane and nor-adamantane based HDAC
      inhibitors were designed, synthesized and screened for the inhibitory activity of
      HDAC. A number of compounds exhibited GI50 of 10-100 nM in human HCT116, NCI-H460
      and U251 cancer cells, in vitro. Compound 32 displays efficacy in human tumour
      animal xenograft model.

PMID- 23538118
TI  - Ultrasound-assisted oxidative desulfurization of bunker-C oil using tert-butyl
      hydroperoxide.
AB  - This work investigated the ultrasonic assisted oxidative desulfurization of
      bunker-C oil with TBHP/MoO3 system. The operational parameters for the
      desulfurization procedure such as ultrasonic irradiation time, ultrasonic wave
      amplitude, catalyst initial concentration and oxidation agent initial
      concentration were studied. The experimental results show that the present
      oxidation system was very efficient for the desulfurization of bunker-C oil and
      ~35% sulfur was removed which was dependent on operational parameters. The
      application of ultrasonic irradiation allowed sulfur removal in a shorter time.
      The stronger the solvent polarity is, the higher the sulfur removal rate, but the
      recovery rate of oil is lower. The sulfur compounds in bunker-C oil reacted with
      TBHP to produce corresponding sulfoxide, and further oxidation produced the
      corresponding sulfone.

PMID- 23538119
TI  - Effects of thermal treatment and sonication on quality attributes of Chokanan
      mango (Mangifera indica L.) juice.
AB  - Ultrasonic treatment is an emerging food processing technology that has growing
      interest among health-conscious consumers. Freshly squeezed Chokanan mango juice
      was thermally treated (at 90  degrees C for 30 and 60s) and sonicated (for 15, 30
      and 60 min at 25  degrees C, 40 kHz frequency, 130 W) to compare the effect on
      microbial inactivation, physicochemical properties, antioxidant activities and
      other quality parameters. After sonication and thermal treatment, no significant
      changes occurred in pH, total soluble solids and titratable acidity. Sonication
      for 15 and 30 min showed significant improvement in selected quality parameters
      except color and ascorbic acid content, when compared to freshly squeezed juice
      (control). A significant increase in extractability of carotenoids (4-9%) and
      polyphenols (30-35%) was observed for juice subjected to ultrasonic treatment for
      15 and 30 min, when compared to the control. In addition, enhancement of radical
      scavenging activity and reducing power was observed in all sonicated juice
      samples regardless of treatment time. Thermal and ultrasonic treatment exhibited
      significant reduction in microbial count of the juice. The results obtained
      support the use of sonication to improve the quality of Chokanan mango juice
      along with safety standard as an alternative to thermal treatment.

PMID- 23538120
TI  - Working towards the development of innovative ultrasound equipment for the
      extraction of virgin olive oil.
AB  - Malaxation has been recognized as one of the most critical points in the
      mechanical extraction process for virgin olive oil (VOO). It is a low and
      continuous kneading of olive paste at a carefully monitored temperature. Through
      this essential technological operation the small droplets of the oil formed
      during the milling merge into large drops that can be easily separated with a
      decanter centrifuge. During this technological phase, a complex and necessary
      bioprocess takes place in order to determine the quality and composition of the
      final product. The malaxer is a heat exchanger characterized by a low overall
      heat transfer coefficient because the ratio of surface area to volume is
      disadvantageous, so it is important to find an innovative technology to improve
      heat-exchange. As matter of fact, the malaxing step is the only discontinuous
      phase in a continuous extraction process. In the next future, the essential
      challenge of VOO industrial plant manufacturing sector is to design and build
      advanced machines in order to transform the discontinuous malaxing step in a
      continuous phase and improve the working capacity of the industrial plants. In
      order to reduce the malaxing time enhancing the quality of the product, two
      ultrasound-assisted virgin olive oil extraction processes were tested against the
      traditional method. The sonication treatment was applied on olives submerged in a
      water bath (before the crushing) and on olive paste (after the crushing). The
      ultrasound technology provides a reduction of the malaxing duration improving VOO
      yields and its minor compounds content. Better extractibility and higher minor
      compounds contents were obtained by sonicating the olives submerged in a water
      bath than olive paste. After experimental trials the results were employed to
      suggest innovative scaling up solutions of the process and new applications of
      ultrasounds in the VOO industry.

PMID- 23538121
TI  - Degradation of 2,4-dinitrophenol using a combination of hydrodynamic cavitation,
      chemical and advanced oxidation processes.
AB  - In the present work, degradation of 2,4-dinitrophenol (DNP), a persistent organic
      contaminant with high toxicity and very low biodegradability has been
      investigated using combination of hydrodynamic cavitation (HC) and
      chemical/advanced oxidation. The cavitating conditions have been generated using
      orifice plate as a cavitating device. Initially, the optimization of basic
      operating parameters have been done by performing experiments over varying inlet
      pressure (over the range of 3-6 bar), temperature (30  degrees C, 35  degrees C
      and 40  degrees C) and solution pH (over the range of 3-11). Subsequently,
      combined treatment strategies have been investigated for process intensification
      of the degradation process. The effect of HC combined with chemical oxidation
      processes such as hydrogen peroxide (HC/H2O2), ferrous activated persulfate
      (HC/Na2S2O8/FeSO4) and HC coupled with advanced oxidation processes such as
      conventional Fenton (HC/FeSO4/H2O2), advanced Fenton (HC/Fe/H2O2) and Fenton-like
      process (HC/CuO/H2O2) on the extent of degradation of DNP have also been
      investigated at optimized conditions of pH 4, temperature of 35  degrees C and
      inlet pressure of 4 bar. Kinetic study revealed that degradation of DNP fitted
      first order kinetics for all the approaches under investigation. Complete
      degradation with maximum rate of DNP degradation has been observed for the
      combined HC/Fenton process. The energy consumption analysis for hydrodynamic
      cavitation based process has been done on the basis of cavitational yield.
      Degradation intermediates have also been identified and quantified in the current
      work. The synergistic index calculated for all the combined processes indicates
      HC/Fenton process is more feasible than the combination of HC with other Fenton
      like processes.

PMID- 23538122
TI  - Poor short term outcome with a metal-on-metal total hip arthroplasty.
AB  - Metal-on-metal (MoM) bearings for total hip arthroplasty (THA) have come under
      scrutiny with reports of high failure rates. Clinical outcome studies with
      several commercially available MoM THA bearings remain unreported. We evaluated
      78 consecutive MoM THAs from a single manufacturer in 68 patients. Sixty-six
      received cobalt-chrome (CoCr) monoblock and 12 received modular titanium
      acetabular cups with internal CoCr liners. Femoral components were titanium with
      modular necks. At average 2.1 years postoperatively, 12 THAs (15.4%) demonstrated
      aseptic failure (10 revisions, 2 revision recommended). All revised hips
      demonstrated capsular necrosis with positive histology reaction for aseptic
      lymphocytic vasculitis-associated lesions/adverse local tissue reactions.
      Prosthetic instability following revision surgery was relatively common. Female
      gender was a strong risk factor for failure, though smaller cups were not. Both
      monoblock and modular components fared poorly. Corrosion was frequently observed
      around the proximal and distal end of the modular femoral necks.

PMID- 23538123
TI  - Outcomes of primary total hip arthroplasty in systemic lupus erythematosus with a
      proximally-coated cementless stem.
AB  - The purpose of this study was to compare the outcomes of total hip arthroplasty
      (THA) in systemic lupus erythematosus (SLE) compared to a cohort of osteonecrosis
      patients who did not have this disease. Between 2001 and 2008, 60 THAs in 44 SLE
      patients who had a mean age of 42 years (range, 18 to 87 years) and a mean follow
      up of 7 years (range, 4 to 11 years) were evaluated. These SLE patients were
      compared to a cohort of 82 THAs in 70 osteonecrosis patients who did not have
      this disease. Outcomes evaluated included implant survivorship, Harris hip
      scores, complications, as well as radiographic results. There was no significant
      difference in implant survivorship (98% vs. 97.5%), Harris hip score (87 vs. 88
      points) and complications (1.7% versus 2.4%) between the SLE and the comparison
      cohort. The authors believe that SLE does not negatively affect the outcomes of
      primary total hip arthroplasty at mid-term follow-up.

PMID- 23538124
TI  - Bone loss during revision of unicompartmental to total knee arthroplasty: an
      analysis of implanted polyethylene thickness from the National Joint Registry
      data.
AB  - Using the National Joint Registry (UK) database, we compared the thickness of
      polyethylene (PE) and the level of constraint used during primary total knee
      arthroplasty (TKA) versus the revision of unicondylar knee arthroplasty (UKA) to
      TKA. A total of 251,803 TKA procedures and 374 revision UKA-TKA procedures
      between 2003 and 2009 were reviewed. The commonest PE size used in TKA was 10mm,
      compared to 12.79 mm in the revision group. The use of constrained knee implant
      was required in 2.15% of primary TKA and 4.19% of UKA to TKA revisions. The
      revision of UKA to TKA is a more complex procedure compared to primary TKA, with
      a higher incidence of using constrained implants and thicker PE inserts. These
      findings may be useful for surgeons in their decision making.

PMID- 23538125
TI  - Forest wildfire, fuel reduction treatments, and landscape carbon stocks: a
      sensitivity analysis.
AB  - Fuel reduction treatments prescribed in fire-suppressed forests of western North
      America pose an apparent paradox with respect to terrestrial carbon management.
      Such treatments have the immediate effect of reducing forest carbon stocks but
      likely reduce future carbon losses through the combustion and mortality caused by
      high-severity wildfires. Assessing the long-term impact of fuel treatment on the
      carbon balance of fire-prone forests has been difficult because of uncertainties
      regarding treatment and wildfire impacts on any given landscape. In this study we
      attempt to remove some of the confusion surrounding this subject by performing a
      sensitivity analysis wherein long-term, landscape-wide carbon stocks are
      simulated under a wide range of treatment efficacy, treatment lifespan, fire
      impacts, forest recovery rates, forest decay rates, and the longevity of wood
      products. Our results indicate a surprising insensitivity of long-term carbon
      stocks to both management and biological variables. After 80 years, a 1600%
      change in either forest growth or decomposition resulted in only a 40% change in
      total system carbon, and a 1600% change in either treatment application rate or
      efficacy in arresting fire spread resulted in only a 10% change in total system
      carbon. This insensitivity of long-term carbon stocks is due in part by the
      infrequency of treatment-wildfire interaction and in part by the controls imposed
      by maximum forest biomass. None of the fuel treatment simulation scenarios
      resulted in increased system carbon.

PMID- 23538126
TI  - Fourier transform infrared spectral evaluation for the differentiation of
      clinically relevant Trichophyton species.
AB  - Routine mold identification methods have been established to provide actual data
      to facilitate reliable diagnoses in clinical laboratories, as well as the
      management of infection and health practice planning, particularly for
      dermatophytes. Some species of the Trichophyton genera, particularly T. rubrum
      and T. mentagrophytes complexes, exhibit more complexity in species recognition.
      In this study, the intriguing technique of Fourier-transform infrared (FT-IR)
      spectroscopy is evaluated for species recognition of Trichophyton spp. A total of
      32 reference isolates, belonging to T. mentagrophytes (n=7), T. rubrum (n=21)
      complexes and Arthroderma spp. (n=4), were included in the study. Numerous
      spectral window FTIR spectroscopy data were analyzed by principal component
      analysis and hierarchical clustering was performed. There were not any spectral
      ranges presenting clusters at the main Trichophyton species (e.g. T. rubrum, T.
      mentagrophytes and Arthroderma spp.). Notably, only T. violaceum (including T.
      yaoundei and T. soudanense) was clustered in several ranges. In intra-species
      evaluation, T. erinacei, belonging to the T. mentagrophytes complex, was
      distinguishable by FT-IR spectroscopy with different spectral range calculations.
      We suggested that further research with several reference and clinical isolates
      of Trichophyton species will be crucial to accurately identify intra-species of
      T. rubrum and T. mentagrophytes complexes.

PMID- 23538127
TI  - Assessment of upper limb function in young Friedreich ataxia patients compared to
      control subjects using a new three-dimensional kinematic protocol.
AB  - BACKGROUND: The assessment of Friedreich ataxia effects on upper limb function in
      clinical follow-up remains a challenging issue. To complete the usual clinical
      scales, an upper limb kinematic protocol adapted to Friedreich ataxia children
      and young adults has been developed and applied to both patients and control
      subjects. METHODS: Nineteen Friedreich ataxia patients (7-24 years old) and
      fifteen healthy controls (9-24) were examined twice during three tasks (drawing,
      pointing, pro-supination) inspired from the "International Cooperative Ataxia
      Rating Scale". A custom-made and adjustable device allowed standardized
      positioning of the subject (in a seated position) and task execution. A three
      dimensional kinematic analysis of the whole upper limb was performed using an
      electromagnetic device. The between session reliability and measurement errors of
      spatiotemporal and angular kinematic parameters were quantified before the
      analysis of their discriminative ability between healthy subjects and patients.
      FINDINGS: Most of the parameters were significantly different between ataxia
      patients and controls, showing the discriminative ability between these two
      populations. In particular, the task duration, the drawing and pointing errors
      were higher for ataxia patients. In most of the cases, the between session
      reliability was found good to excellent for the spatiotemporal parameters and
      moderate to excellent for the kinematic parameters. INTERPRETATION: Kinematic
      differences have been pointed out between Friedreich ataxia patients and
      controls, leading to a better understanding of the effect of this pathology on
      upper limb function. Discriminative ability and reliability of the developed
      protocol were demonstrated for many parameters, making it a relevant tool for
      clinical follow-up.

PMID- 23538128
TI  - Variability in inter-joint coordination during walking of elderly adults and its
      association with clinical balance measures.
AB  - BACKGROUND: Walking requires coordination among multiple joints. Little is known
      about the association between the coordination ability and fall risks in elderly
      adults. This study investigated variability of inter-joint coordination in
      elderly adults and determined its correlation to clinical balance measures.
      METHODS: Gait analyses of 15 non-fallers and 15 fallers were performed during
      walking. Continuous relative phase, derived from phase angles of two adjacent
      joints, was used to assess the inter-joint coordination. Variability of inter
      joint coordination was calculated as the average standard deviation of all points
      on the ensemble continuous relative phase curve over a gait cycle, namely the
      deviation phase. Outcomes from three clinical balance tests, including Berg
      Balance Test, Dynamic Gait Index and Timed Up-and-Go, were examined. FINDINGS: No
      significant group differences were detected in hip-knee deviation phase values
      after accounting for differences in walking speeds. For the knee-ankle deviation
      phase, fallers demonstrated significantly greater values in the stance phase but
      smaller values in the swing phase. The hip-knee deviation phase values
      demonstrated a negative correlation with Dynamic Gait Index, and the knee-ankle
      deviation phase values had a negative correlation with Dynamic Gait Index and a
      positive correlation with Timed Up-and-Go time. INTERPRETATION: Excessive
      variability of the supporting limb and reduced variability of the swing limb in
      knee-ankle inter-joint coordination of fallers may contribute to their risk of
      imbalance or tripping during walking. Compared to Berg Balance Test and Timed Up
      and-Go, Dynamic Gait Index scores might be more sensitive to reflect declines in
      inter-joint coordination during walking.

PMID- 23538129
TI  - Making the case for inclusive design.
AB  - This paper describes the University of Cambridge, Engineering Design Centre's
      (EDC) case for inclusive design, based on 10 years of research, promotion and
      knowledge transfer. In summary, inclusive design applies an understanding of
      customer diversity to inform decisions throughout the development process, in
      order to better satisfy the needs of more people. Products that are more
      inclusive can reach a wider market, improve customer satisfaction and drive
      business success. The rapidly ageing population increases the importance of this
      approach. The case presented here has helped to convince BT, Nestle and others to
      adopt an inclusive approach. 

PMID- 23538130
TI  - Identification of the lateral position of a virtual object based on echoes by
      humans.
AB  - Echolocation offers a promising approach to improve the quality of life of people
      with blindness although little is known about the factors influencing object
      localisation using a 'searching' strategy. In this paper, we describe a series of
      experiments using sighted and blind human listeners and a 'virtual auditory
      space' technique to investigate the effects of the distance and orientation of a
      reflective object and the effect of stimulus bandwidth on ability to identify the
      right-versus-left position of the object, with bands of noise and durations from
      10-400 ms. We found that performance reduced with increasing object distance.
      This was more rapid for object orientations where mirror-like reflection paths do
      not exist to both ears (i.e., most possible orientations); performance with these
      orientations was indistinguishable from chance at 1.8 m for even the best
      performing listeners in other conditions. Above-chance performance extended to
      larger distances when the echo was artificially presented in isolation, as might
      be achieved in practice by an assistive device. We also found that performance
      was primarily based on information above 2 kHz. Further research should extend
      these investigations to include other factors that are relevant to real-life
      echolocation.

PMID- 23538131
TI  - Clinical aspects of an autosomal dominantly inherited hearing impairment linked
      to the DFNA60 locus on chromosome 2q23.1-2q23.3.
AB  - A total of 64 loci for autosomal dominant non-syndromic hearing impairment have
      been described, and the causative genes have been identified for 24 of these. The
      present study reports on the clinical characteristics of an autosomal dominantly
      inherited hearing impairment that is linked to a region within the DFNA60 locus
      located on chromosome 2 in q22.1-24.1. A pedigree spanning four generations was
      established with 13 affected individuals. Linkage analysis demonstrated that the
      locus extended over a 2.96 Mb region flanked by markers D2S2335 and D2S2275. The
      audiograms mainly showed a distinctive U-shaped configuration. Deterioration of
      hearing started at a wide age range, from 12 to 40 years. Cross-sectional
      analysis showed rapid progression of hearing impairment from mild to severe,
      between the ages of 40 and 60 years, a phenomenon that is also observed in DFNA9
      patients. The results of the individual longitudinal analyses were generally in
      line with those obtained by the cross-sectional analysis. Speech recognition
      scores related to the level of hearing impairment (PTA1,2,4 kHz) appeared to be
      fairly similar to those of presbyacusis patients. It is speculated that hearing
      impairment starting in mid-life, as shown by DFNA60 patients, could play a role
      in the development of presbyacusis. Furthermore, speech recognition did not
      deteriorate appreciably before the sixth decade of life. We conclude that DFNA60
      should be considered in hearing impaired patients who undergo a rapid progression
      in middle age and are negative for DFNA9. Furthermore, cochlear implantation
      resulted in good rehabilitation in two DFNA60 patients.

PMID- 23538133
TI  - [Gastric cancer risk estimate in patients with chronic gastritis associated with
      Helicobacter pylori infection in a clinical setting].
AB  - BACKGROUND/AIM: Severity of chronic gastritis associated with Helicobacter pylori
      infection (CGAHpI) could play a role in evaluating the potential risk to develop
      gastric cancer. Our aim was to estimate the risk for gastric cancer in a clinical
      setting, according to histopathologic criteria, by applying the gastric cancer
      risk index (GCRI) METHODS: Histopathologic study of the gastric biopsies (corpus
      antrum) from consecutive adult patients that underwent gastroesophageal
      duodenoscopy was carried out, and the GCRI was applied in patients presenting
      with CGAHpI. RESULTS: One hundred eleven patients (77% female) with a mean age of
      38.6+/-13.1 years were included. Active Helicobacter pylori infection (aHpi) was
      diagnosed in 77 cases (69.40%). In 45% of the cases with aHpi, pangastritis (23%)
      or corpus-predominant gastritis (22%) was diagnosed. Nine cases were diagnosed
      with intestinal metaplasia (8%), 7 of which (77.70%) were in the aHpi group.
      Twenty one percent of the patients with aHpi had a GCRI of 2 (18.10%) or 3
      (2.50%) points (high risk index), while 79.10% accumulated a GCRI of 0 or 1
      points (low risk index). Of the patients with no aHpi, none of them had 3 points
      (p=0.001). Of the 18 patients that accumulated 2 or 3 points, 6 (33.30%)
      presented with intestinal metaplasia (all with pangastritis and corpus
      predominant gastritis), of which 4 cases (66.60%) had aHpi. CONCLUSIONS: The
      estimated gastric cancer risk in patients with CGAHpI in the clinical setting
      studied was relatively low and 5% of the patients had a histopathologic phenotype
      associated with an elevated risk for developing gastric cancer.

PMID- 23538132
TI  - NCLX: the mitochondrial sodium calcium exchanger.
AB  - The free Ca(2+) concentration within the mitochondrial matrix ([Ca(2+)]m)
      regulates the rate of ATP production and other [Ca(2+)]m sensitive processes. It
      is set by the balance between total Ca(2+) influx (through the mitochondrial
      Ca(2+) uniporter (MCU) and any other influx pathways) and the total Ca(2+) efflux
      (by the mitochondrial Na(+)/Ca(2+) exchanger and any other efflux pathways). Here
      we review and analyze the experimental evidence reported over the past 40years
      which suggest that in the heart and many other mammalian tissues a putative
      Na(+)/Ca(2+) exchanger is the major pathway for Ca(2+) efflux from the
      mitochondrial matrix. We discuss those reports with respect to a recent discovery
      that the protein product of the human FLJ22233 gene mediates such Na(+)/Ca(2+)
      exchange across the mitochondrial inner membrane. Among its many functional
      similarities to other Na(+)/Ca(2+) exchanger proteins is a unique feature: it
      efficiently mediates Li(+)/Ca(2+) exchange (as well as Na(+)/Ca(2+) exchange) and
      was therefore named NCLX. The discovery of NCLX provides both the identity of a
      novel protein and new molecular means of studying various unresolved quantitative
      aspects of mitochondrial Ca(2+) movement out of the matrix. Quantitative and
      qualitative features of NCLX are discussed as is the controversy regarding the
      stoichiometry of the NCLX Na(+)/Ca(2+) exchange, the electrogenicity of NCLX, the
      [Na(+)]i dependency of NCLX and the magnitude of NCLX Ca(2+) efflux. Metabolic
      features attributable to NCLX and the physiological implication of the Ca(2+)
      efflux rate via NCLX during systole and diastole are also briefly discussed.

PMID- 23538134
TI  - Metabolic regulation of circadian clocks.
AB  - Circadian clocks are 24-h timekeeping mechanisms, which have evolved in plants,
      animals, fungi and bacteria to anticipate changes in light and temperature
      associated with the rotation of the Earth. The current paradigm to explain how
      biological clocks provide timing information is based on multiple interlocking
      transcription-translation negative feedback loops (TTFL), which drive rhythmic
      gene expression and circadian behaviour of growth and physiology. Metabolism is
      an important circadian output, which in plants includes photosynthesis, starch
      metabolism, nutrient assimilation and redox homeostasis. There is increasing
      evidence in a range of organisms that these metabolic outputs can also contribute
      to circadian timing and might also comprise independent circadian oscillators. In
      this review, we summarise the mechanisms of circadian regulation of metabolism by
      TTFL and consider increasing evidence that rhythmic metabolism contributes to the
      circadian network. We highlight how this might be relevant to plant circadian
      clock function. 

PMID- 23538135
TI  - Bioaccessibility of mercury in selected Ayurvedic medicines.
AB  - Five Ayurvedic medicines with mercury concentrations of 85mg/kg and higher were
      characterized with respect to their speciation and their bioaccessibility. X-ray
      absorption spectroscopy revealed that the mercury in the Ayurvedic medicines was
      inorganic and best matched to cinnabar, even in samples that had been
      hypothesized to contain mercury through plant sources only. The bioaccessibility
      (bioaccessible concentrations and percent bioaccessibility) was measured using
      two methods: a two-phase physiologically based extraction test (PBET gastric, G
      and gastric+intestinal phase, GI); and the fed organic estimation human
      simulation test (FOREhST). The percent bioaccessibility of mercury in all
      Ayurvedic samples was very low (<5%), corresponding to the low solubility of
      cinnabar, but it increased with increasing dissolved organic carbon content of
      the bioaccessibility solutions (PBET-G<PBET-GI<FOREhST). Filtration of FOREhST
      solutions reduced the bioaccessible mercury concentrations to undetectable values
      for most of the Ayurvedic samples. Incorporation of percent relative
      bioaccessibility of mercury into risk calculations decreased daily intake
      estimates by 29-900 times, and reduced them to acceptable levels for three of the
      five medicines.

PMID- 23538136
TI  - The effects of triclosan on spore germination and hyphal growth of the arbuscular
      mycorrhizal fungus Glomus intraradices.
AB  - The effect of triclosan (5-chloro-2-[2,4-dichlorophenoxy]phenol; TCS), on spore
      germination, hyphal growth, and hyphal branching of the arbuscular mycorrhizal
      (AM) fungus, Glomus intraradices spores was evaluated at exposure concentrations
      of 0.4 and 4.0 MUg/L in a static renewal exposure system. To determine if
      potential effects were mycotoxic or a consequence of impaired signaling between a
      host plant and the fungal symbiont, spores were incubated with and without the
      addition of a root exudate. Exposed spores were harvested at days 7, 14, and 21.
      AM spore germination, hyphal growth, and hyphal branching were significantly
      lower in both TCS concentrations compared to controls in non-root exudate
      treatments suggesting direct mycotoxic effects of TCS on AM development. Greater
      hyphal growth and hyphal branching in controls and 0.4MUg/L TCS treatments with
      root exudate compared to non-root exudate treatments demonstrated growth
      stimulation by signaling chemicals present in the root exudate. This stimulatory
      effect was absent in the 4.0 MUg/L TCS treatments indicating a direct effect on
      plant signaling compounds or plant signal response.

PMID- 23538137
TI  - A computational fluid dynamic modelling approach to assess the representativeness
      of urban monitoring stations.
AB  - Air quality measurements of urban monitoring stations have a limited spatial
      representativeness due to the complexity of urban meteorology and emissions
      distribution. In this work, a methodology based on a set of computational fluid
      dynamics simulations based on Reynolds-Averaged Navier-Stokes equations (RANS
      CFD) for different meteorological conditions covering several months is developed
      in order to analyse the spatial representativeness of urban monitoring stations
      and to complement their measured concentrations. The methodology has been applied
      to two urban areas nearby air quality traffic-oriented stations in Pamplona and
      Madrid (Spain) to analyse nitrogen oxides concentrations. The computed maps of
      pollutant concentrations around each station show strong spatial variability
      being very difficult to comply with the European legislation concerning the
      spatial representativeness of traffic-oriented air quality stations.

PMID- 23538139
TI  - Reply to the letter to the editor from Foray and Colin, entitled 'Relationship
      between radiosensitivity, initial DNA damage, apoptosis and gene expression:
      between reproducible works and technical artefacts': genetics are essential in
      the response of normal tissues to radiation.

PMID- 23538138
TI  - Relationship of estimated dietary intake of n-3 polyunsaturated fatty acids from
      fish with peripheral nerve function after adjusting for mercury exposure.
AB  - BACKGROUND: Some clinical studies have suggested that ingestion of n-3
      polyunsaturated fatty acids (PUFA) has neuroprotective effects on peripheral
      nerve function. However, few epidemiological studies have examined the effect of
      dietary n-3 PUFA intake from fish consumption on peripheral nerve function, and
      none have controlled for co-occurrence of methylmercury exposure from fish
      consumption. OBJECTIVES: We evaluated the effect of estimated dietary n-3 PUFA
      intake on peripheral nerve function after adjusting for biomarkers of
      methylmercury and elemental mercury in a convenience sample of 515 dental
      professionals. METHODS: We measured sensory nerve conduction (peak latency and
      amplitude) of the median, ulnar and sural nerves and total mercury concentrations
      in hair and urine samples. We estimated daily intake (mg/day) of the total n-3
      PUFA, n-3 docosahexaenoic acid (DHA), and n-3 eicosapentaenoic acid (EPA) based
      on a self-administrated fish consumption frequency questionnaire. We also
      collected information on mercury exposure, demographics and other covariates.
      RESULTS: The estimated median intakes of total n-3 PUFA, n-3 EPA, and n-3 DHA
      were 447, 105, and 179 mg/day, respectively. The mean mercury concentrations in
      urine (1.05 MUg/L) and hair (0.49 MUg/g) were not significantly different from
      the US general population. We found no consistent association between n-3 PUFA
      intake and sensory nerve conduction after adjusting for mercury concentrations in
      hair and urine although some positive associations were observed with the sural
      nerve. CONCLUSIONS: In a convenience sample of dental professionals, we found
      little evidence suggesting that dietary intake of n-3 PUFAs from fish has any
      impact on peripheral nerve function after adjustment for methylmercury exposure
      from fish and elemental mercury exposure from dental amalgam.

PMID- 23538140
TI  - Early predictors of alterations in left atrial structure and function related to
      left ventricular dysfunction in asymptomatic patients with hypertension.
AB  - Our aim was to investigate the relationships between left atrial (LA) structural
      and functional changes and left ventricular (LV) dysfunction related to LV
      pressure overload in asymptomatic patients with hypertension. One hundred and
      twenty-six asymptomatic patients with hypertension and LV ejection fraction (EF)
      >= 60% were studied. Conventional, pulsed and tissue Doppler, and two-dimensional
      speckle-tracking echocardiography (2DSTE) were performed to seek the independent
      determinants for alterations in LA structure and function. LA volume index (LAVI)
      correlated with age, body mass index (BMI), end-diastolic ventricular septal
      thickness (VSth), end-diastolic LV posterior wall thickness, relative LV wall
      thickness (RWT), LV mass index, peak A velocity of transmitral flow, E/e', and
      peak systolic and early diastolic LA strains and strain rates. Peak LA strain
      during ventricular systole (S-LAs) correlated with age, BMI, heart rate (HR), end
      systolic LV diameter, LAVI, VSth, RWT, LVEF, e', E/e', peak systolic LV radial
      strain, and peak early diastolic LV longitudinal strain rate. Multivariate
      regression analyses indicated that LV mass index, peak A velocity, E/e', and S
      LAs are defined as strong predictors related to LAVI, and that BMI, HR, LAVI, and
      peak systolic LV radial strain are defined as strong predictors related to S-LAs.
      In conclusion, 2DSTE demonstrated that alterations in LA structure and function
      are mainly associated with LV diastolic and systolic dysfunction, respectively,
      in preclinical patients with hypertension.

PMID- 23538141
TI  - Intracellular angiotensin II increases the total potassium current and the
      resting potential of arterial myocytes from vascular resistance vessels of the
      rat. Physiological and pathological implications.
AB  - The influence of intracellular and extracellular administration of angiotensin II
      (Ang II; 10(-9) M) on total potassium current of arterial myocytes isolated from
      mesenteric arteries of Sprague Dawley rats was investigated. Measurements of
      total potassium current were performed using the voltage clamp whole cell
      configuration while the effect of intracellular Ang II on the resting potential
      of arterial myocytes was measured using the current clamp configuration of
      pCLAMP. The results indicated that: 1) intracellular Ang II (10(-9) M) increased
      the total potassium current by 73% +/- 2.6% (n = 22; P < .05) within 5 minutes;
      2) concurrently with the increment of potassium current, the resting potential
      was increased by 7 +/- 1.5 mV (n = 23; P < .05); 3) extracellular administration
      of Ang II (10(-9) M) reduced the total potassium current by 20% +/- 1.6% (n = 21;
      P < .05) within 5 minutes and depolarized the smooth muscle cells by 9 +/- 2.3 mV
      (n = 26; P < .05); 4) the effects of intracellular Ang II on potassium current
      and membrane potential were inhibited by dialyzing a PKA inhibitor (10(-9) M)
      inside the cell together with Ang II (10(-9) M; P > .05); 5) valsartan (10(-9) M)
      dialyzed into the cell together with Ang II (10(-9) M) abolished the effect of
      the peptide on potassium current and membrane potential. The presence of
      endogenous or internalized intracellular Ang II in vascular resistance vessels
      and its effect on potassium current and resting potential indicates that the
      peptide present inside the arterial myocytes plays an important role on the
      regulation of vascular tone and consequently on peripheral resistance, which is a
      determining factor in the regulation of arterial blood pressure.

PMID- 23538142
TI  - The potential roles of saturating and supersaturating contrast-response functions
      in conjunction detection: reply to Peirce.

PMID- 23538143
TI  - Nonlinear response functions can still be used to build conjunction detectors:
      reply to May and Zhaoping.

PMID- 23538146
TI  - Gentle touch activates the anterior prefrontal cortex: an NIRS study.
AB  - Gentle touching of the hand activates emotion- and reward-related regions of the
      brain. The present study investigated activation of the prefrontal cortex by
      gentle sweeps of the palm or forearm with three materials (wood, velvet,
      paintbrush) using near-infrared spectroscopy (NIRS). Sweeps of the left palm with
      a sensuous velvet fabric increased the oxy-hemoglobin (oxy-Hb) concentration in
      the frontal-polar cortex (FPC) and a part of the orbitofrontal cortex (OFC),
      compared to a neutral touch produced by rounded wood. Pleasantness ratings were
      higher for the velvet than wood. In conclusion, the present study revealed the
      involvement of the FPC/OFC in pleasant emotion produced by gentle touch to the
      hand.

PMID- 23538147
TI  - Hemodialysis duration, human platelet antigen HPA-3 and IgA isotype of anti
      beta2glycoprotein I antibodies are associated with native arteriovenous fistula
      failure in Tunisian hemodialysis patients.
AB  - INTRODUCTION: Arteriovenous fistula (AVF) failure is a major cause of morbidity
      and mortality in hemodialysis patients. We assessed the role of a large panel of
      acquired and inherited thrombophilic markers in cases of AVF thrombosis among 101
      Tunisians on chronic hemodialysis, all with native AVF. MATERIALS AND METHODS: In
      this case-control study, we considered the levels of fibrinogen, factor II,
      factor VII, factor VIII, factor IX, factor X, factor XI, factor XII, von
      Willebrand factor, natural coagulation inhibitors, D-Dimer, homocysteine, IgG,
      IgM and IgA anticardiolipin and anti-beta2glycoprotein I (anti-beta2GPI), and
      anti-H/PF4 antibodies; the presence of Lupus Anticoagulant; and genetic markers
      (Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C). RESULTS:
      Multivariate analysis indicated that dialysis for >69 months (OR=10.12; 95% CI,
      2.53 to 40.52; p=0.001), HPA-3aa genotype (OR=3.58; 95% CI, 1.36 to 9.4; p=0.01)
      and anti-beta2GPI IgA isotype (OR=3.4; 95% CI, 1.21 to 9.55; p=0.02) were
      independent risk factors for AVF thrombosis in Tunisian hemodialysis patients.
      Kaplan-Meier analysis showed that AVF survival was significantly lower for
      patients with anti-beta2GPI IgA than for patients without this isotype (log-rank
      test, p=0.014). CONCLUSIONS: IgA anti-beta2GPI may be of clinical relevance among
      Tunisians. Further studies on the polymorphism of beta2GPI and HPA systems would
      be helpful for identifying patient groups at high risk of AVF failure.

PMID- 23538148
TI  - Predicting adoption of exposure therapy in a randomized controlled dissemination
      trial.
AB  - The present study examined organizational, client, and therapist characteristics
      as predictors of use of and proficiency in exposure therapy (ET) after training.
      Therapists naive to ET (N=181) were randomized to: (1) online training (OLT), (2)
      OLT plus motivational enhancement (ME), or (3) OLT+ME plus a learning community.
      Twelve weeks after training, self-reported use of ET in clinical practice was
      high (87.5%) and therapists demonstrated moderate clinical proficiency. Use of ET
      was predicted by therapist degree, self-efficacy, and knowledge. Clinical
      proficiency was predicted by therapist anxiety sensitivity, attitudes, and
      knowledge, as well as organizational and client barriers. Several of these
      effects were moderated by training condition, indicating that therapists who
      received more comprehensive training were less impacted by barriers and showed
      enhanced adoption in the presence of facilitating factors. Overall, these results
      suggest that the primary barriers to the adoption of ET are therapist, not
      organizational or client, factors. 

PMID- 23538150
TI  - On EEPs and e-blasts, cluster publishing, consensus and interventional
      cardiology.

PMID- 23538149
TI  - Consensus on recording of gas permeable contact lens fit.
AB  - PURPOSE: To develop a new schematic scheme for efficiently recording the key
      parameters of gas permeable contact lens (GP) fits based on current consensus.
      METHODS: Over 100 established GP fitters and educators met to discuss the
      parameters proposed in educational material for evaluating GP fit and concluded
      on the key parameters that should be recorded. The accuracy and variability of
      evaluating the fluorescein pattern of GP fit was determined by having 35
      experienced contact lens practitioners from across the world, grading 5 images of
      a range of fits and the topographer simulation of the same fits, in random, order
      using the proposed scheme. The accuracy of the grading was compared to objective
      image analysis of the fluorescein intensity of the same images. RESULTS: The key
      information to record to adequately describe the fit of an GP was agreed as: the
      manufacturer, brand and lens parameters; settling time; comfort on a 5 point
      scale; centration; movement on blink on a +/-2 scale; and the Primary Fluorescein
      Pattern in the central, mid-peripheral and edge regions of the lens averaged
      along the horizontal and vertical lens axes, on a +/-2 scale. On average 50-60%
      of practitioners selected the median grade when subjectively rating fluorescein
      intensity and this was correlated to objective quantification (r=0.602, p<0.001).
      Objective grading suggesting horizontal median fluorescein intensity was
      generally symmetrical, as was the vertical meridian, but this was not the case
      for subjective grading. Simulated fluorescein patterns were subjectively and
      objectively graded as being less intense than real photographs (p<0.01).
      CONCLUSION: GP fit recording can be standardised and simplified to enhance GP
      practice.

PMID- 23538151
TI  - Does a hybrid approach to multivessel revascularisation really make sense?

PMID- 23538152
TI  - Rethinking overdilation of drug-eluting stents: an effective "loose end".

PMID- 23538153
TI  - EAPCI: sharing experience together, the radial approach consensus.

PMID- 23538154
TI  - Influence of transradial versus transfemoral diagnostic heart catheterisation on
      peripheral vascular endothelial function.
AB  - AIMS: Endothelium dysfunction has been reported in patients (pts) undergoing
      transradial catheterisation. Alterations of the hand microcirculation possibly
      associated with systemic inflammation have never previously been reported. We
      aimed at investigating possible alteration of hand endothelial microcirculation
      secondary to transradial heart catheterisation. METHODS AND RESULTS: We
      randomised 40 pts with stable angina undergoing coronary angiography to either
      transradial (TR, n=20) or transfemoral (TF, n=20) approach. At baseline (BL), 24
      hours (24 hrs) and 30 days (FU: follow-up) after catheterisation we assessed: a)
      peripheral endothelial function (EndoScore [ES]) by peripheral arterial tonometry
      (EndoPAT); b) biomarkers of endothelial turnover (sE-Selectin) and inflammation
      (hs-CRP). No clinical or angiographic differences were observed between the two
      groups. At 24 hours, ES (BL: 0.42+/-0.27 vs. 24 hours: 0.27+/-0.19, p<0.05)
      significantly decreased in the TR group, but not in the TF group (BL: 0.44+/-0.34
      vs. 24 hours: 0.45+/-0.39, n.s.). Both sE-Selectin and hs-CRP increased
      significantly at 24 hours in all pts. At 30 days, we observed in the TR group a
      restoration of ES (FU: 0.44+/-0.34, n.s. vs. BL; p<0.05 vs. 24 hours), while no
      difference was observed in the TF group. A reduction towards baseline was
      observed in both groups of sE-Selectin and hs-CRP. CONCLUSIONS: A transient
      impairment of the digital microcirculatory endothelial function is observed in
      patients undergoing transradial diagnostic catheterisation, beyond local
      mechanical injury at the arterial access and on top of the systemic inflammatory
      response associated with heart catheterisation.

PMID- 23538155
TI  - Acute procedural and six-month clinical outcome in patients treated with a
      dedicated bifurcation stent for left main stem disease: the TRYTON LM multicentre
      registry.
AB  - AIMS: Tryton side branch (SB) reverse culotte stenting has been employed for the
      treatment of left main (LM) stem bifurcations in patients at high risk for bypass
      surgery. The aim of this study was to assess acute angiographic results and six
      month clinical outcome after implantation of the Tryton stent in the LM. METHODS
      AND RESULTS: We studied 52 consecutive patients with LM disease treated in nine
      European centres. Angiographic and clinical data analysis was performed
      centrally. Fifty-one of 52 patients (age 68+/-11 yrs, 75% male, 42% unstable
      angina, SYNTAX score 20+/-8) were successfully treated with the Tryton stent.
      Medina class was 1,1,1 in 33 (63%), 1,0,1 in 7 (13%), 1,1,0 in 3 (6%), 0,1,1 in 8
      (4%) and 0,0,1 in 1 (2%). The Tryton stent on a stepped balloon (diameter 3.5-2.5
      mm) was used in 41/51 (80%) of cases. The mean main vessel stent diameter was
      3.4+/-0.4 mm with an everolimus-eluting stent employed in 30/51 (59%) of cases.
      Final kissing balloon dilatation was performed in 48/51 (94%). Acute gain was
      1.52+/-0.86 mm in the LM and 0.92+/-0.47 mm in the SB. The angiographic success
      rate was 100%; the procedural success rate reached 94%. Periprocedural MI
      occurred in three patients. At six-month follow-up, the TLR rate was 12%, MI 10%
      and cardiac death 2%. The hierarchical MACE rate at six months was 22%. No cases
      of definite stent thrombosis occurred. CONCLUSIONS: The use of the Tryton stent
      for treatment of LM bifurcation disease in combination with a conventional drug
      eluting stent is feasible and achieves an optimal angiographic result. Safety of
      the procedure and six-month outcome are acceptable in this high-risk lesion PCI.
      Further safety and efficacy studies with long-term outcome assessment of this
      strategy are warranted.

PMID- 23538156
TI  - Long-term efficacy of transcatheter closure of ventricular septal defect in
      combination with percutaneous coronary intervention in patients with ventricular
      septal defect complicating acute myocardial infarction: a multicentre study.
AB  - AIMS: To assess the immediate and long-term outcomes of transcatheter closure of
      ventricular septal defect (VSD) in combination with percutaneous coronary
      intervention (PCI) in patients with VSD complicating acute myocardial infarction
      (AMI). METHODS AND RESULTS: Data were prospectively collected from 35 AMI
      patients who underwent attempted transcatheter VSD closure and PCI therapy in
      five high-volume heart centres. All the patients who survived the procedures were
      followed up by chest x-ray, electrocardiogram and echocardiography. Thirteen
      patients underwent urgent VSD closure in the acute phase (within two weeks from
      VSD) while the others underwent elective closure at a median of 23 days from VSD
      occurrence. The percentage of VSD closure device success was 92.3% (36/39) and
      procedure success was 91.4% (32/35). The incidence of in-hospital mortality was
      14.3% (5/35). At a median of 53 months follow-up, only two patients died at 38
      and 41 months, respectively, and other patients' cardiac function tested by
      echocardiography improved significantly compared to that evaluated before
      discharge. CONCLUSION: The combination of transcatheter VSD closure and PCI for
      treating VSD complicating AMI is safe and feasible and is a promising alternative
      to surgery in patients with anatomically suitable VSD and coronary lesion.

PMID- 23538157
TI  - Residual SYNTAX score after PCI for triple vessel coronary artery disease:
      quantifying the adverse effect of incomplete revascularisation.
AB  - AIMS: There is some evidence to suggest that incompleteness of coronary artery
      revascularisation after PCI is associated with inferior outcomes. The SYNTAX
      score was developed as a tool to quantify the extent of coronary artery disease
      in the SYNTAX study. We aimed to use this score to quantify the completeness of
      revascularisation after PCI (the "residual SYNTAX score") and to determine its
      impact upon mortality. METHODS AND RESULTS: We studied 240 consecutive patients
      with native three-vessel disease who underwent PCI between 2003 and 2008. SYNTAX
      scores prior to, and after, PCI were calculated, the difference (DeltaSYNTAX)
      being a measure of the relative completeness of revascularisation. Median follow
      up was 2.6 (1.2-3.2) years; 21% of patients were surgical turndowns, and 38% were
      non-elective. A residual (rSYNTAX) score of zero (full revascularisation) was
      achieved in 40% and median rSYNTAX was 3.5 (0-10.9). At final follow-up reduced
      mortality was found in patients with rSYNTAX 0 vs. others (2.5 vs. 12%,
      respectively, p=0.003) and for those with rSYNTAX<median vs.>median (3 vs. 11%,
      p=0.003). rSYNTAX was an independent predictor of mortality in a multivariate
      analysis, whereas baseline SYNTAX score was not. CONCLUSIONS: The residual SYNTAX
      score is a useful method to quantify incomplete revascularisation in patients
      undergoing PCI for 3VD. Complete revascularisation (rSYNTAX=0) is achieved in
      only a minority and, for them, the mortality rate is low.

PMID- 23538158
TI  - Impact of infarct-related artery patency before primary PCI on outcome in
      patients with ST-segment elevation myocardial infarction: the HORIZONS-AMI trial.
AB  - AIMS: We assessed the impact of early infarct-related artery (IRA) recanalisation
      on the outcomes of patients in the recently conducted, large-scale, multicentre
      HORIZONS-AMI trial. METHODS AND RESULTS: Of the 3,602 patients enrolled in the
      HORIZONS-AMI trial, 3,093 patients (85.9%) were treated with percutaneous
      coronary intervention (PCI) to a single artery. We analysed one-year outcomes in
      these patients according to the presence or absence of early IRA patency, defined
      as Thrombolysis in Myocardial Infarction (TIMI) 2 or 3 flow in the IRA. Baseline
      coronary angiography showed early IRA patency in 1,121 patients (36.2%), while
      1,972 patients (63.8%) had TIMI 0 or 1 flow. The presence compared with the
      absence of early IRA patency was associated with better angiographic results
      after primary PCI with more TIMI 3 flow after PCI (93.2% vs. 82.9%, p<0.0001) and
      myocardial blush grade 2 or 3 (84.4% vs. 71.1%, p<0.0001). Early IRA patency was
      associated with lower rates of one-year mortality (2.5% vs. 3.9%, p=0.04) and
      definite or probable stent thrombosis (2.0% vs. 4.0%, p=0.002). In multivariable
      analysis, early IRA patency at baseline angiography was an independent predictor
      of reduced mortality at one year (HR 0.58, 95% CI: 0.36-0.98, p=0.02).
      CONCLUSIONS: Early IRA patency in patients with STEMI undergoing primary PCI is
      associated with better TIMI flow and myocardial blush post PCI and is an
      independent predictor of lower one-year mortality. ClinicalTrials.gov identifier
      NCT00433966.

PMID- 23538159
TI  - Incidence, predictors and management of left main coronary artery stent
      restenosis: a comprehensive review in the era of drug-eluting stents.
AB  - International guidelines recommend surgical revascularisation for unprotected
      left main (ULM) coronary artery disease. The introduction of drug-eluting stents
      (DES) as an emergency therapy has resulted in increasing numbers of patients
      having stents placed in ULM. As a consequence, important data on the safety and
      long-term outcome of PCI for ULM have progressively accumulated over recent
      years, derived mainly from registries rather than prospective randomised trials.
      These studies indicate that restenosis of the ULM still represents the main
      predictor of clinical events following stenting. However, the observed incidence
      is highly variable amongst the published studies and there is little data about
      the clinical management of restenosis of stents placed in the ULM. In the present
      paper we review the available literature regarding ULM restenosis, identify its
      predictors and suggest an algorithm for optimal management.

PMID- 23538160
TI  - Hybrid revascularisation in multivessel coronary artery disease: could a
      combination of CABG and PCI be the best option in selected patients?

PMID- 23538161
TI  - How should I treat a restenosis after superficial femoral artery stenting?

PMID- 23538162
TI  - Activating glucocorticoid receptor-ERK signaling pathway contributes to
      ginsenoside Rg1 protection against beta-amyloid peptide-induced human endothelial
      cells apoptosis.
AB  - The deposition of beta-amyloid (Abeta) in neurons and vascular cells of the brain
      has been characterized in Alzheimer's disease. Ginsenoside Rg1 (Rg1) is an active
      components in Panax ginseng, a famous traditional Chinese medicines recorded in
      Compendium of Materia Medica. Present study attempted to evaluate the potential
      mechanisms of Abeta-mediated insult and the protective effects of Rg1 on human
      endothelial cells. Rg1 attenuated the Abeta25-35-associated mitochondrial
      apoptotic events, accompanied by inhibiting HIF-1alpha expression followed by
      intracellular reactive nitrogen species generation, and protein
      nitrotyrosination. These protective effects were abolished by glucocorticoid
      receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than estrogen
      receptor alpha antagonist ICI 82,780. Taken together, our results suggested that
      Rg1 protected against Abeta25-35-induced apoptosis at least in part by two
      complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating HIF
      1alpha initiated protein nitrotyrosination, and (2) inhibiting mitochondrial
      apoptotic cascades. These data provided a novel insight to the mechanisms of
      Rg1protective effects on Abeta25-35-induced endothelial cells apoptosis,
      suggesting that GR-ERK signaling pathway might play an important role in it.

PMID- 23538163
TI  - Inhibitory effects of the root extract of Litsea cubeba (lour.) pers. on adjuvant
      arthritis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Litsea cubeba (Lour.) Pers.
      (Family Lauraceae) has long been used as a folk remedy in Traditional Chinese
      Medicine (TCM) and Dai Ethnopharmacy for the treatment of rheumatic diseases in
      southwestern China. AIM OF THE STUDY: This study investigated the preventive
      efficacy of Litsea cubeba root in treating rheumatoid arthritis using Freund's
      complete adjuvant (CFA) induced arthritis (AA) in rat model. MATERIALS AND
      METHODS: Arthritis was induced in male Wistar rats by immunization with CFA.
      Ethanol extract (EELC) and water extract (WELC) of Litsea cubeba root both at
      50mg/kg and 200mg/kg were orally administered from a day after the induction of
      arthritis. Paw swelling, arthritic score, body weight growth rate, index of
      thymus and spleen were observed, and the production of TNF-alpha, IL-1beta, IL-6
      and IL-10 in serum were measured by enzyme-linked immunosorbent assay. The
      expression levels of inflammatory enzymes like cyclooxygenase and lipoxygenase
      were also measured by enzyme-linked immunosorbent assay. Moreover, histological
      changes in the ankle joint were analyzed in AA rats. RESULTS: Both EELC and WELC
      significantly suppressed paw swelling and arthritic score, increased the loss in
      body weight and decreased the index of thymus. Histopathological improvement in
      joint architecture was also observed in EELC, WELC-treated AA rats. The
      expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) were
      decreased on treatment with EELC and WELC. Furthermore, the overproduction of TNF
      alpha, IL-1beta and IL-6 were remarkably attenuated in serum of all Litsea cubeba
      treated rats, however, IL-10 was markedly increased at doses of 50mg/kg of EELC
      and WELC. CONCLUSIONS: These results indicate that extract of Litsea cubeba root
      significantly attenuates adjuvant arthritis in rats by decreasing the levels of
      TNF-alpha, IL-1beta and IL-6 and increasing of IL-10 in serum as well as down
      regulate the levels of inflammatory enzymes such as COX-2 and 5-LOX. This
      suggests that Litsea cubeba root might be used as a therapeutic agent for the
      treatment of human arthritis.

PMID- 23538164
TI  - Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted
      their integration into the cultural heritage of native rural Spain as inferred by
      vernacular names diversity, traditions, and mitochondrial DNA.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Beetles of the family Meloidae (blister beetles)
      are often reported in pharmacological literature because of their content of
      cantharidin. Cantharidin has a long history in human medicine and was commonly
      applied in the 19th and the early 20th centuries, although its use has been
      progressively abandoned since then. Contrary to most, even common, large species
      of Coleoptera, blister beetles of the genera Berberomeloe, Physomeloe and to a
      lesser extent Meloe, are usually recognized and often incorporated into local
      folk taxonomy by inhabitants of rural areas in Spain. AIM OF THE STUDY: To
      demonstrate the role that pharmacological properties of blister beetles must have
      played in their integration in the culture of early Iberian human societies, but
      also in the preservation of their identity until today, a rare case for Spanish
      insects. To achieve this purpose we document the diversity of vernacular names
      applied in rural areas of Spain, and we determine, using molecular data, the
      antiquity of the presence of two species of the better-known blister beetle in
      rural Spain, Berberomeloe majalis and Berberomeloe insignis. MATERIALS AND
      METHODS: We try to document the extent of traditional knowledge of meloid beetles
      in rural areas by interviewing about 120 people from villages in central and
      southern Spain. We also use mitochondrial DNA sequences (Cytochrome Oxidase I and
      16SrRNA) obtained from several populations of two species of the better known
      blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis, to
      determine whether these beetles were already present in the Iberian Peninsula
      when earlier ancient cultures were developing. RESULTS: Our results show that,
      based on mitochondrial DNA, blister beetles of the genus Berberomeloe were
      present in the Iberian Peninsula long before humans arrived, so ancient Iberian
      cultures were in contact with the same beetle species occurring now in rural
      areas. On the other hand, people interviewed in rural communities provided us
      with more than 28 different vernacular names, a few short songs incorporated to
      local folklore, and some therapeutic uses. CONCLUSIONS: Current knowledge of
      blister beetles of the family Meloidae in rural Spain was likely developed as a
      consequence of their pharmacological properties; we hypothesize this knowledge
      was inherited from ancient pre-Christian Iberian native cultures as part of their
      traditional therapeutic traditions. It is possible then, that current vernacular
      names and traditional songs are the only remnants of an ancient knowledge of
      pharmacological uses of meloid beetles, verbally transmitted from the ancestral
      cultures to modern day rural Spain. Our work suggests that this legacy, part of
      the European Cultural Heritage, is disappearing fast, in parallel to the loss of
      traditional agricultural techniques.

PMID- 23538165
TI  - Anti-inflammatory activity of ethyl acetate fraction of the seeds of Brucea
      Javanica.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Brucea javanica (L.) Merr. (Yadanzi
      in Chinese) have been used for the treatment of inflammation, dysentery, malaria,
      and cancer in Chinese traditional medicine. However, the anti-inflammatory
      mechanism of Brucea javanica has not been fully elucidated. This study examined
      the anti-inflammatory activity of ethyl acetate fraction of the seeds of Brucea
      javanica (EA-BJ) in vitro and in vivo. MATERIALS AND METHODS: The anti
      inflammatory activity of EA-BJ and its ability to modulate the production of NO,
      PGE2, TNF-alpha, IL-1beta, IL-6 and IL-10 inflammatory mediators in
      lipopolysaccharide-activated RAW 264.7 macrophage were evaluated. Moreover, the
      anti-inflammatory activity of EA-BJ was also in vivo assayed by carrageenan
      induced paw edema in mice. RESULTS: In vitro assays showed remarkable anti
      inflammatory activity of EA-BJ, through the inhibition of production of NO, PGE2,
      TNF-alpha, IL-1beta and IL-6 inflammatory mediators and induction of production
      of IL-10 anti-inflammatory cytokine. In vivo assays showed anti-inflammatory
      activity for decrement of the paw edema in carrageenan induced paw edema test.
      CONCLUSION: The results obtained in vitro and in vivo showed that possible anti
      inflammatory effects of EA-BJ may be attributed to inhibition pro-inflammatory
      mediators production, NO, PGE2, TNF-alpha, IL-1beta and IL-6 and to increase
      production of IL-10 anti-inflammatory cytokine. The seeds of Brucea javanica may
      thus prove beneficial in the treatment of inflammatory diseases.

PMID- 23538166
TI  - Modification of forsythia detaching factor by gingival crevicular fluid in
      periodontitis.
AB  - OBJECTIVES: Forsythia detaching factor (FDF) is a virulence factor of Tannerella
      forsythia detected as a mixture of the 60-kDa form of FDF and the 28-kDa C
      terminal fragment (FDFc). The objective of the present study was to clarify the
      proteolytic activity of gingival crevicular fluid (GCF) from patients with
      periodontitis and healthy subjects using recombinant FDF (rFDF) as substrate.
      DESIGN: Eleven patients with periodontitis and 6 healthy subjects were recruited.
      Modification of rFDF and subsequent production of rFDFc by proteolytic activity
      of GCF was determined by Western blotting. Proteolytic activity of GCF was
      evaluated using an Ac-Arg-Ala-Lys-p-nitroaniline substrate. Correlation analysis
      between two different sets of variables was performed. Variables used in this
      analysis were proteolytic activity, clinical parameters, relative band density of
      rFDFc and those of rFDF. RESULTS: Proteolytic activity in GCF was significantly
      higher in patients with periodontitis than in healthy subjects. Production of
      rFDFc was determined by treatment of rFDF with GCF from patients with
      periodontitis and with GCF from healthy subjects. Correlations between clinical
      parameters and proteolytic activity in GCF were significantly positive. On the
      other hand, correlations between relative band density of rFDFc or rFDF on
      Western blot and cleaving activity or clinical parameters were significantly
      negative. CONCLUSION: The detected extend of GCF-activity generating rFDFc from
      rFDF and/or even further degrading rFDF correlates with severity of
      periodontitis.

PMID- 23538167
TI  - Coronary CT angiography versus standard of care for assessment of chest pain in
      the emergency department.
AB  - Use of coronary CT angiography (CTA) in the early evaluation of low-intermediate
      risk chest pain in the emergency department represents a common, appropriate
      application of CTA in the community. Three large randomized trials (CT-STAT,
      ACRIN-PA, and ROMICAT II) have compared a coronary CTA strategy with current
      standard of care evaluations in >3000 patients. These trials consistently show
      the safety of a negative coronary CT angiogram to identify patients for discharge
      from the emergency department with low rates of major adverse cardiovascular
      events, at significantly lower cost, and greater efficiency in terms of time to
      discharge. Together, these trials provide definitive evidence for the use of
      coronary CTA in the emergency department in patients with a low-to-intermediate
      pretest probability of coronary artery disease. Clinical practice guidelines that
      recommend the use of coronary CTA in the emergency department are warranted.

PMID- 23538168
TI  - Prulifloxacin versus levofloxacin in the treatment of severe COPD patients with
      acute exacerbations of chronic bronchitis.
AB  - RATIONALE: Antimicrobial therapy of chronic bronchitis exacerbations in patients
      with severe chronic obstructive pulmonary disease (COPD) is based on empiric
      antibiotic treatment. OBJECTIVES: To evaluate the efficacy of prulifloxacin
      versus levofloxacin therapy in severe COPD patients with exacerbations of chronic
      bronchitis. METHODS: This study involved a multicenter, parallel, double-blind,
      randomized clinical trial. Patients aged 40 years or older, smokers, or ex
      smokers (>10 pack-years) with spirometrically confirmed severe COPD (FEV1 <= 50%
      predicted and FEV1/FVC ratio < 0.7) and diagnosed with an acute exacerbation of
      chronic bronchitis were enrolled in the study. Patients were randomized to
      receive prulifloxacin 600 mg once a day or levofloxacin 500 mg once a day for 7
      days. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was clinical
      assessment at the TOC visit (7-10 days after the end of treatment) of signs and
      symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough
      and body temperature assessed through semi-quantitative scales. The ITT
      population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated
      subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with
      levofloxacin (96.5%) were considered cured at TOC (the difference in the
      percentage of cured patients was -3.98 with 95%CI of -8.76; 0.79). At the 6-month
      follow-up, the rates of patients with no relapse of AECB were higher than 95% in
      both the prulifloxacin and levofloxacin groups. CONCLUSIONS: Both prulifloxacin
      and levofloxacin showed efficacy rates higher than 90% in the treatment of severe
      COPD patients with exacerbations of chronic bronchitis, with no statistically
      significant differences between the two antibiotics. The long-term follow-up
      confirmed a very low incidence of relapse, endorsing the appropriateness of this
      therapeutic approach. EUDRACT no. 2006-004167-56.

PMID- 23538169
TI  - Down-regulated expression of AQP5 on lung in rat DIC model induced by LPS and its
      effect on the development of pulmonary edema.
AB  - Disseminated intravascular coagulation (DIC) is an acquired syndrome
      characterized by the widespread activation of coagulation, which leads to failure
      of multiple organs in the body. DIC of rat with lipopolysaccharide (LPS) is
      associated with subsequent pulmonary edema. Lung tissue is highly water permeable
      and expresses several aquaporins (AQPs). We therefore explored whether AQP5
      involved in the pathogenesis of LPS-induced lung edema. The rats were
      intravenously infused with LPS (30 mg/kg) for 4 h, 6 h, 8 h, 10 h, and 12 h to
      induce DIC. Platelets count (PLT), D-Dimer (DD), fibrinogen (FIB), prothrombin
      time (PT), and activated partial thromboplastin time (APTT) were determined. Real
      time quantitative PCR and Western blot were used to analyze the mRNA and protein
      expression of AQP5. Lung samples were stained with hematoxylin-eosin and lung
      wet/dry weight (W/D) ratios were measured. Here, we demonstrated that PLT and FIB
      values were significant decreased, the values for DD, PT, and APTT were marked
      increased, microthrombus was observed in lung specimens, and simultaneously with
      the AQP5 showed down-regulated expression following LPS infused from 4 h to 12 h.
      However, histopathological changes such as pulmonary edema and the increased lung
      W/D weight ratio were observed after LPS infused from 6 h to 12 h. These results
      indicated that the decreased expression of AQP5 maybe induce liquid transport
      obstacles between alveolar and capillary, and provides the report of AQP5 gene
      regulation, revealing the pathogenesis of pulmonary edema in DIC model of rat.

PMID- 23538170
TI  - Pharmacodynamics of GSK961081, a bi-functional molecule, in patients with COPD.
AB  - GSK961081 is an inhaled bi-functional molecule with both muscarinic antagonism
      and beta2-agonism (MABA) properties. This randomised, double-blind, double-dummy,
      crossover study evaluated 14 days treatment with the MABA GSK961081 400 MUg and
      1200 MUg once daily and tiotropium 18 MUg once daily plus salmeterol 50 MUg twice
      daily (TIO + SAL), versus placebo in 50 patients with moderate COPD. The primary
      endpoint was forced expiratory volume in 1 s (FEV1) at 24 h on Days 1 and 14.
      MABA 400 (n = 29), MABA 1200 (n = 32) and TIO + SAL (n = 41) resulted in
      significant increases in FEV1 over 24 h. Mean (95% CI) 24 h trough FEV1 (L)
      values relative to placebo (n = 43) were, for Day 1, MABA 400: 0.141 (0.060,
      0.222); MABA 1200: 0.184 (0.105, 0.263); TIO + SAL: 0.162 (0.092, 0.231); for Day
      14, MABA 400: 0.115 (0.024, 0.205); MABA 1200: 0.168 (0.080, 0.255); TIO + SAL:
      0.103 (0.026, 0.180). Onset of bronchodilation was faster for both MABA doses
      versus TIO + SAL. No clinically relevant systemic pharmacodynamic effects were
      observed. Adverse events were similar across groups; however tremor (n = 2, MABA
      1200), dysgeusia (n = 2, MABA 1200; n = 2, MABA 400) and dry mouth (n = 1, MABA
      1200) were reported after GSK961081 only. GSK961081 demonstrated sustained
      bronchodilation similar to TIO + SAL, but with a more rapid onset, and was well
      tolerated at the tested doses.

PMID- 23538171
TI  - Goodbye ISAAC, farewell Joseph.

PMID- 23538173
TI  - An interview with Jane Richardson.

PMID- 23538172
TI  - Intersection of identities: food, role, and the African-American pastor.
AB  - African-American pastors can foster health-related innovations as gatekeepers and
      advocates within their churches. Personal experiences with food and health likely
      influence their support of such programs. Identities or meanings attached to
      societal roles have been shown to motivate individuals' attitudes and behaviors.
      Understanding role and eating identities of African-American pastors may have
      important implications for participation in faith-based health promotion
      programs. This study aimed to describe the eating and pastoral identities of
      African-American pastors, explore intersections between these identities, and
      highlight implications for nutrition programs. In-depth interviews with 30
      African-American pastors were audio-recorded and transcribed verbatim. Data were
      analyzed using theory-guided and grounded-theory approaches. Pastors described
      affinity across one or more dimensions including healthy, picky, meat, and over
      eater identities. In describing themselves as pastors, the dimensions pastor's
      heart, teacher, motivator, and role model emerged. Pastors who described
      themselves as healthy eaters were more likely to see themselves as role models.
      Pastors with healthier eating identities and more complex pastoral identities
      described greater support for health programming while unhealthy, picky, and over
      eaters did not. These findings provide guidance for understanding eating and role
      identities among pastors and should be considered when designing and implementing
      faith-based programs.

PMID- 23538174
TI  - Improving the quality of papers published in pharmacoeconomics and outcomes
      research.

PMID- 23538175
TI  - Consolidated Health Economic Evaluation Reporting Standards (CHEERS)--explanation
      and elaboration: a report of the ISPOR Health Economic Evaluation Publication
      Guidelines Good Reporting Practices Task Force.
AB  - BACKGROUND: Economic evaluations of health interventions pose a particular
      challenge for reporting because substantial information must be conveyed to allow
      scrutiny of study findings. Despite a growth in published reports, existing
      reporting guidelines are not widely adopted. There is also a need to consolidate
      and update existing guidelines and promote their use in a user-friendly manner. A
      checklist is one way to help authors, editors, and peer reviewers use guidelines
      to improve reporting. OBJECTIVE: The task force's overall goal was to provide
      recommendations to optimize the reporting of health economic evaluations. The
      Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is
      an attempt to consolidate and update previous health economic evaluation
      guidelines into one current, useful reporting guidance. The CHEERS Elaboration
      and Explanation Report of the ISPOR Health Economic Evaluation Publication
      Guidelines Good Reporting Practices Task Force facilitates the use of the CHEERS
      statement by providing examples and explanations for each recommendation. The
      primary audiences for the CHEERS statement are researchers reporting economic
      evaluations and the editors and peer reviewers assessing them for publication.
      METHODS: The need for new reporting guidance was identified by a survey of
      medical editors. Previously published checklists or guidance documents related to
      reporting economic evaluations were identified from a systematic review and
      subsequent survey of task force members. A list of possible items from these
      efforts was created. A two-round, modified Delphi Panel with representatives from
      academia, clinical practice, industry, and government, as well as the editorial
      community, was used to identify a minimum set of items important for reporting
      from the larger list. RESULTS: Out of 44 candidate items, 24 items and
      accompanying recommendations were developed, with some specific recommendations
      for single study-based and model-based economic evaluations. The final
      recommendations are subdivided into six main categories: 1) title and abstract,
      2) introduction, 3) methods, 4) results, 5) discussion, and 6) other. The
      recommendations are contained in the CHEERS statement, a user-friendly 24-item
      checklist. The task force report provides explanation and elaboration, as well as
      an example for each recommendation. The ISPOR CHEERS statement is available
      online via Value in Health or the ISPOR Health Economic Evaluation Publication
      Guidelines Good Reporting Practices - CHEERS Task Force webpage
      (http://www.ispor.org/TaskForces/EconomicPubGuidelines.asp). CONCLUSIONS: We hope
      that the ISPOR CHEERS statement and the accompanying task force report guidance
      will lead to more consistent and transparent reporting, and ultimately, better
      health decisions. To facilitate wider dissemination and uptake of this guidance,
      we are copublishing the CHEERS statement across 10 health economics and medical
      journals. We encourage other journals and groups to consider endorsing the CHEERS
      statement. The author team plans to review the checklist for an update in 5
      years.

PMID- 23538176
TI  - The comparison of trial data-based and registry data-based cost-effectiveness of
      infliximab treatment for rheumatoid arthritis in Sweden using a modeling
      approach.
AB  - OBJECTIVE: To evaluate the precision of the predictive cost-effectiveness
      assessment based on a phase 3 clinical trial with infliximab for the treatment of
      rheumatoid arthritis in Swedish clinical practice. METHODS: Three patient cohorts
      were identified: the patients included in the infliximab trial (ATTRACT),
      patients initially treated with infliximab from a Swedish registry (STURE), a
      subset of these registry patients meeting inclusion criteria for the ATTRACT
      trial was the third patient cohort; two sets of assumptions in relation to the
      efficacy data were evaluated: "ATTRACT" (efficacy data over the duration of the
      trial) and "STURE" (effectiveness data over 10 years). In addition, the impact of
      including the placebo effect for the comparator was evaluated as a basis for the
      calculation of cost-effectiveness by using a modeling approach. A health economic
      model was utilized to estimate the cost per quality-adjusted life-year (QALY)
      gained. RESULTS: The results for the three patient cohorts ranged from cost
      saving to a cost per QALY gained of ?2,400 and ?24,900 to ?26,000 when the
      ATTRACT and STURE assumptions were used, respectively. Sensitivity analyses
      indicated that the inclusion of placebo effect had the largest effect on the
      results, increasing the cost per QALY gained to approximately ?50,000 for all
      patient cohorts. CONCLUSIONS: The treatment effect of infliximab measured in
      clinical trials and clinical practice results in comparable cost-effectiveness
      ratios, as calculated by using a modeling approach, whereas the assumptions made
      in relation to the effectiveness data and the chosen comparator have a large
      impact on the results. This reinforces the value of early modeling studies based
      on randomized clinical trial data, but assumptions made need to be carefully
      assessed.

PMID- 23538177
TI  - Evaluating the impact of unmeasured confounding with internal validation data: an
      example cost evaluation in type 2 diabetes.
AB  - The quantitative assessment of the potential influence of unmeasured confounders
      in the analysis of observational data is rare, despite reliance on the "no
      unmeasured confounders" assumption. In a recent comparison of costs of care
      between two treatments for type 2 diabetes using a health care claims database,
      propensity score matching was implemented to adjust for selection bias though it
      was noted that information on baseline glycemic control was not available for the
      propensity model. Using data from a linked laboratory file, data on this
      potential "unmeasured confounder" were obtained for a small subset of the
      original sample. By using this information, we demonstrate how Bayesian modeling,
      propensity score calibration, and multiple imputation can utilize this additional
      information to perform sensitivity analyses to quantitatively assess the
      potential impact of unmeasured confounding. Bayesian regression models were
      developed to utilize the internal validation data as informative prior
      distributions for all parameters, retaining information on the correlation
      between the confounder and other covariates. While assumptions supporting the use
      of propensity score calibration were not met in this sample, the use of Bayesian
      modeling and multiple imputation provided consistent results, suggesting that the
      lack of data on the unmeasured confounder did not have a strong impact on the
      original analysis, due to the lack of strong correlation between the confounder
      and the cost outcome variable. Bayesian modeling with informative priors and
      multiple imputation may be useful tools for unmeasured confounding sensitivity
      analysis in these situations. Further research to understand the operating
      characteristics of these methods in a variety of situations, however, remains.

PMID- 23538178
TI  - Cost-effectiveness analysis of early versus late total hip replacement in Italy.
AB  - OBJECTIVE: To assess the cost-effectiveness of early primary total hip
      replacement (THR) for functionally independent older adult patients with
      osteoarthritis (OA) versus 1) nonsurgical therapy followed by THR once the
      patient has progressed to a functionally dependent state ("delayed THR") and 2)
      nonsurgical therapy alone ('medical therapy'), from the Italian National Health
      Service perspective. METHODS: Individual patient data and evidence from published
      literature on disease progression, economic costs and THR outcomes in OA,
      including utilities, perioperative mortality rates, prosthesis survival, and
      costs of prostheses, THR, rehabilitation, follow-up, revision, and nonsurgical
      management, combined with population life tables, were synthesized in a Markov
      model of OA. The model represents the lifetime experience of a patient cohort
      following their treatment choice, discounting costs and benefits (quality
      adjusted life-years) at 3% annually. RESULTS: At age 65 years, the incremental
      cost per quality-adjusted life-year of THR over delayed THR was ?987 in men and
      ?466 in women; the figures for delayed THR versus medical therapy were ?463 and
      ?82, respectively. Among 80-year-olds, early THR is (extended) dominant. With
      gradual utility loss after primary THR, delaying surgery may be more appealing in
      women than in men in their 50s, because longer female life expectancy implies
      longer latter periods of low health-related quality of life (HRQOL) with early
      THR. CONCLUSIONS: THR is cost-effective. Patients' HRQOL benefits forgone with
      delayed THR are worth more than the costs it saves to the Italian National Health
      Service. This analysis might help to explain women's consistently lower HRQOL by
      the time of primary operation.

PMID- 23538179
TI  - Hospitalization resource use and costs before and after TIA and stroke: results
      from a population-based cohort study (OXVASC).
AB  - OBJECTIVES: High hospitalization rates, prolonged length of stay, and increased
      risks of subsequent events mean a steep increase in health care usage after
      stroke. No study, however, has examined to what extent increased costs after
      transient ischemic attack (TIA) or stroke are due to hospitalizations for the
      initial event, recurrent events, and/or nonvascular hospitalizations, and how
      costs compare with the year prior to the event. METHODS: We studied patients in a
      population-based cohort study (Oxford Vascular Study) in the United Kingdom from
      2003 to 2007. Hospitalization and cost details were obtained from patients'
      individualized Hospital Episode Statistics records. RESULTS: A total of 295
      incident TIA and 439 incident stroke patients were included. For patients with
      stroke, average costs increased from L1437 in the year pre-event to L6629 in the
      year post-event (P<0.0001). Sixty-four percent (L4224) of poststroke costs were
      due to hospitalizations linked to the index stroke, more than 30% of which were
      given nonvascular primary diagnoses on Hospital Episode Statistics, and L653
      (10%) were due to hospitalizations linked to subsequent vascular events. For
      patients with TIA, costs increased from L876 1 year before the event to L2410 in
      the year post-event (P<0.0001). Patients with TIA incurred nonsignificantly
      higher costs due to hospitalizations linked to subsequent vascular events (L774)
      than for hospitalizations linked to the index TIA (L720). CONCLUSIONS: Hospital
      costs increased after TIA or stroke, primarily because of increased initial
      cerebrovascular hospitalizations. The finding that costs due to nonvascular
      diagnoses also increased after TIA or stroke appears, in part, to be explained by
      the miscoding of TIA/stroke-related hospitalizations in electronic information
      systems.

PMID- 23538180
TI  - Cost-effectiveness of cetuximab, cetuximab plus irinotecan, and panitumumab for
      third and further lines of treatment for KRAS wild-type patients with metastatic
      colorectal cancer.
AB  - OBJECTIVES: To estimate the cost-effectiveness of cetuximab monotherapy,
      cetuximab plus irinotecan, and panitumumab monotherapy compared with best
      supportive care (BSC) for the third and subsequent lines of treatment of patients
      with Kirsten rat sarcoma wild-type metastatic colorectal cancer from the
      perspective of the UK National Health Service. METHODS: An "an area under the
      curve" cost-effectiveness model was developed. The clinical effectiveness
      evidence for both cetuximab and panitumumab was taken from a single randomized
      controlled trial (RCT) in each case and for cetuximab plus irinotecan from
      several sources. RESULTS: Patients are predicted to survive for approximately 6
      months on BSC, 8.5 months on panitumumab, 10 months on cetuximab, and 16.5 months
      on cetuximab plus irinotecan. Panitumumab is dominated, and cetuximab is extended
      dominated. An incremental cost-effectiveness ratio (ICER) of L95,000 per quality
      adjusted life-year (QALY) was estimated for cetuximab versus BSC and is likely to
      be relatively accurate, because the relevant clinical evidence is taken from a
      high-quality RCT. The estimated ICER for panitumumab versus BSC, at L187,000 per
      QALY, is less certain due to assumptions in the adjustment for the substantial
      crossing-over of patients in the RCT. The ICER for cetuximab plus irinotecan
      versus BSC, at L88,000 per QALY, is least certain due to substantial uncertainty
      about progression-free survival, treatment duration, and overall survival.
      Nonetheless, when key parameters are varied within plausible ranges, all three
      treatments always remain poor value for money. CONCLUSIONS: All three treatments
      are highly unlikely to be considered cost-effective in this patient population in
      the United Kingdom. We explain how the reader can adapt the model for other
      countries.

PMID- 23538181
TI  - Cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the
      treatment of Clostridium difficile infection in the United States.
AB  - OBJECTIVES: Fidaxomicin is a novel treatment for Clostridium difficile infections
      (CDIs). This new treatment, however, is associated with a higher acquisition cost
      compared with alternatives. The objective of this study was to evaluate the cost
      effectiveness of fidaxomicin or oral vancomycin for the treatment of CDIs.
      METHODS: We performed a cost-utility analysis comparing fidaxomicin with oral
      vancomycin for the treatment of CDIs in the United States by creating a decision
      analytic model from the third-party payer perspective. RESULTS: The incremental
      cost-effectiveness ratio with fidaxomicin compared with oral vancomycin was
      $67,576/quality-adjusted life-year. A probabilistic Monte Carlo sensitivity
      analysis showed that fidaxomicin had an 80.2% chance of being cost-effective at a
      willingness-to-pay threshold of $100,000/quality-adjusted life-year. Fidaxomicin
      remained cost-effective under all fluctuations of both fidaxomicin and oral
      vancomycin costs. The decision analytic model was sensitive to variations in
      clinical cure and recurrence rates. Secondary analyses revealed that fidaxomicin
      was cost-effective in patients receiving concominant antimicrobials, in patients
      with mild to moderate CDIs, and when compared with oral metronidazole in patients
      with mild to moderate disease. Fidaxomicin was dominated by oral vancomycin if
      CDI was caused by the NAP1/Bl/027 Clostridium difficile strain and was dominant
      in institutions that did not compound oral vancomycin. CONCLUSION: Results of our
      model showed that fidaxomicin may be a more cost-effective option for the
      treatment of CDIs when compared with oral vancomycin under most scenarios tested.

PMID- 23538182
TI  - Economic measurement of medical errors using a hospital claims database.
AB  - OBJECTIVE: The primary objective of this study was to estimate the occurrence and
      costs of medical errors from the hospital perspective. METHODS: Methods from a
      recent actuarial study of medical errors were used to identify medical injuries.
      A visit qualified as an injury visit if at least 1 of 97 injury groupings
      occurred at that visit, and the percentage of injuries caused by medical error
      was estimated. Visits with more than four injuries were removed from the
      population to avoid overestimation of cost. Population estimates were
      extrapolated from the Premier hospital database to all US acute care hospitals.
      RESULTS: There were an estimated 161,655 medical errors in 2008 and 170,201
      medical errors in 2009. Extrapolated to the entire US population, there were more
      than 4 million unique injury visits containing more than 1 million unique medical
      errors each year. This analysis estimated that the total annual cost of
      measurable medical errors in the United States was $985 million in 2008 and just
      over $1 billion in 2009. The median cost per error to hospitals was $892 for 2008
      and rose to $939 in 2009. Nearly one third of all medical injuries were due to
      error in each year. CONCLUSIONS: Medical errors directly impact patient outcomes
      and hospitals' profitability, especially since 2008 when Medicare stopped
      reimbursing hospitals for care related to certain preventable medical errors.
      Hospitals must rigorously analyze causes of medical errors and implement
      comprehensive preventative programs to reduce their occurrence as the financial
      burden of medical errors shifts to hospitals.

PMID- 23538183
TI  - Cost-effectiveness of a program to eliminate disparities in pneumococcal
      vaccination rates in elderly minority populations: an exploratory analysis.
AB  - OBJECTIVE: Invasive pneumococcal disease is a major cause of preventable
      morbidity and mortality in the United States, particularly among the elderly (>65
      years). There are large racial disparities in pneumococcal vaccination rates in
      this population. Here, we estimate the cost-effectiveness of a hypothetical
      national vaccination intervention program designed to eliminate racial
      disparities in pneumococcal vaccination in the elderly. METHODS: In an
      exploratory analysis, a Markov decision-analysis model was developed, taking a
      societal perspective and assuming a 1-year cycle length, 10-year vaccination
      program duration, and lifetime time horizon. In the base-case analysis, it was
      conservatively assumed that vaccination program promotion costs were $10 per
      targeted minority elder per year, regardless of prior vaccination status and
      resulted in the elderly African American and Hispanic pneumococcal vaccination
      rate matching the elderly Caucasian vaccination rate (65%) in year 10 of the
      program. RESULTS: The incremental cost-effectiveness of the vaccination program
      relative to no program was $45,161 per quality-adjusted life-year gained in the
      base-case analysis. In probabilistic sensitivity analyses, the likelihood of the
      vaccination program being cost-effective at willingness-to-pay thresholds of
      $50,000 and $100,000 per quality-adjusted life-year gained was 64% and 100%,
      respectively. CONCLUSIONS: In a conservative analysis biased against the
      vaccination program, a national vaccination intervention program to ameliorate
      racial disparities in pneumococcal vaccination would be cost-effective.

PMID- 23538184
TI  - Cost-effectiveness of enhancing adherence to therapy with blood pressure-lowering
      drugs in the setting of primary cardiovascular prevention.
AB  - OBJECTIVE: To estimate the cost-effectiveness of enhancing adherence to blood
      pressure (BP)-lowering drug therapy in a large population without signs of
      preexisting cardiovascular (CV) disease. METHODS: A cohort of 209,650 patients
      aged 40 to 79 years resident in the Italian Region of Lombardia and newly treated
      with BP-lowering drugs during 2000 to 2001 was followed from index prescription
      to 2007. During the follow-up, the 10,688 patients who experienced a
      hospitalization for a coronary or cerebrovascular event were identified
      (outcome). Adherence was measured by the proportion of days covered by the
      therapy with BP-lowering drugs. The cost-effectiveness of enhancing adherence was
      measured through the incremental cost-effectiveness ratio. RESULTS: Enhancing
      adherence from 52% (baseline) to 60% and 80% led to a reduced rate for CV
      outcomes (from 85 to 83 and 77 events every 10,000 person-year, respectively) and
      increased the cost for drug therapy (from ?1,325k to ?1,507k and ?1,934k every
      10,000 person-year, respectively). The resulting incremental cost-effectiveness
      ratio decreased from ?76k (95% confidence interval ?74k-?77k) to ?74k (95%
      confidence interval ?72k-?75k) for each CV event avoided by enhancing adherence
      from baseline to 60% and 80%, respectively. CONCLUSIONS: Enhancing adherence to
      BP-lowering medications in the setting of primary CV prevention might offer
      important benefits in reducing the risk of CV outcome, but at a substantial cost.

PMID- 23538185
TI  - The cost-effectiveness of the levonorgestrel-releasing intrauterine system for
      the treatment of idiopathic heavy menstrual bleeding in the United States.
AB  - OBJECTIVES: Heavy menstrual bleeding negatively impacts the health and quality of
      life of about 18 million women in the United States. Although some studies have
      established the clinical effectiveness of heavy menstrual bleeding treatments,
      few have evaluated their cost-effectiveness. Our objective was to evaluate the
      cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS)
      compared with other therapies for idiopathic heavy menstrual bleeding. METHODS:
      We developed a model comparing the clinical and economic outcomes (from a US
      payer perspective) of three broad initial treatment strategies over 5 years: LNG
      IUS, oral agents, or surgery. Up to three nonsurgical treatment lines, followed
      by up to two surgical lines, were allowed; unintended pregnancy was possible, and
      women could discontinue any time during nonsurgical treatments. Menstrual blood
      loss of 80 ml or more per cycle determined treatment failure. RESULTS: Initiating
      treatment with LNG-IUS resulted in the fewest hysterectomies (6 per 1000 women),
      the most quality-adjusted life-years (3.78), and the lowest costs ($1137) among
      all the nonsurgical strategies. Initiating treatment with LNG-IUS was also less
      costly than surgery, resulted in fewer hysterectomies (vs. 9 per 1000 for
      ablation) but was associated with fewer quality-adjusted life-years gained per
      patient (vs. 3.80 and 3.88 for ablation and hysterectomy, respectively).
      Sensitivity analyses confirmed these results. CONCLUSIONS: LNG-IUS resulted in
      the lowest treatment costs and the fewest number of hysterectomies performed over
      5 years compared with all other initial strategies and resulted in the most
      quality-adjusted life-years gained among nonsurgical options. Initial treatment
      with LNG-IUS is the least costly and most effective option for women desiring to
      preserve their fertility.

PMID- 23538186
TI  - The cost-effectiveness of duloxetine in chronic low back pain: a US private payer
      perspective.
AB  - OBJECTIVE: To assess the cost-effectiveness of duloxetine in the treatment of
      chronic low back pain (CLBP) from a US private payer perspective. METHODS: A cost
      utility analysis was undertaken for duloxetine and seven oral post-first-line
      comparators, including nonsteroidal anti-inflammatory drugs (NSAIDs), weak and
      strong opioids, and an anticonvulsant. We created a Markov model on the basis of
      the National Institute for Health and Clinical Excellence model documented in its
      2008 osteoarthritis clinical guidelines. Health states included treatment, death,
      and 12 states associated with serious adverse events (AEs). We estimated
      treatment-specific utilities by carrying out a meta-analysis of pain scores from
      CLBP clinical trials and developing a transfer-to-utility equation using
      duloxetine CLBP patient-level data. Probabilities of AEs were taken from the
      National Institute for Health and Clinical Excellence model or estimated from
      osteoarthritis clinical trials by using a novel maximum-likelihood simulation
      technique. Costs were gathered from Red Book, Agency for Healthcare Research and
      Quality's Healthcare Cost and Utilization Project database, the literature, and,
      for a limited number of inputs, expert opinion. The model performed one-way and
      probabilistic sensitivity analyses and generated incremental cost-effectiveness
      ratios (ICERs) and cost acceptability curves. RESULTS: The model estimated an
      ICER of $59,473 for duloxetine over naproxen. ICERs under $30,000 were estimated
      for duloxetine over non-NSAIDs, with duloxetine dominating all strong opioids. In
      subpopulations at a higher risk of NSAID-related AEs, the ICER over naproxen was
      $33,105 or lower. CONCLUSIONS: Duloxetine appears to be a cost-effective post
      first-line treatment for CLBP compared with all but generic NSAIDs. In
      subpopulations at risk of NSAID-related AEs, it is particularly cost-effective.

PMID- 23538187
TI  - Understanding the costs of care for cystic fibrosis: an analysis by age and
      health state.
AB  - OBJECTIVES: Cystic fibrosis (CF) is an inherited disease that requires more
      intensive treatments as the disease progresses. Recent medical advancements have
      improved survival but have also increased costs. Our lack of understanding on the
      relationship between disease severity and lifetime health care costs is a major
      impediment to the timely economic assessment of new treatments. METHODS: Using
      data from three waves of the Australian Cystic Fibrosis Australia Data Registry,
      we estimate the annual costs of CF care by age and health state. We define health
      states on the basis of annual lung-function scores and patient's organ transplant
      status. We exploit the longitudinal nature of the data to model disease
      progression, and we use this to estimate lifetime health care costs. RESULTS: The
      mean annual health care cost for treating CF is US $15,571. Costs for patients
      with mild, moderate, and severe disease are US $10,151, US $25,647, and US
      $33,691, respectively. Lifetime health care costs are approximately US $306,332
      (3.5% discount rate). The majority of costs are accounted for by hospital
      inpatients (58%), followed by pharmaceuticals (29%), medical services (10%),
      complications (2%), and diagnostic tests (1%). CONCLUSIONS: Our study is the
      first of its kind using the Australian Cystic Fibrosis Data Registry, and
      demonstrates the utility of longitudinal registry data for the purpose of
      economic analysis. Our results can be used as an input to future economic
      evaluations by providing analysts with a better understanding of the long-term
      cost impact when new treatments are developed.

PMID- 23538188
TI  - The cost-effectiveness of a novel SIAscopic diagnostic aid for the management of
      pigmented skin lesions in primary care: a decision-analytic model.
AB  - OBJECTIVES: Pigmented skin lesions are commonly presented in primary care.
      Appropriate diagnosis and management is challenging because the vast majority are
      benign. The MoleMate system is a handheld SIAscopy scanner integrated with a
      primary care diagnostic algorithm aimed at improving the management of pigmented
      skin lesions in primary care. METHODS: This decision-model-based economic
      evaluation draws on the results of a randomized controlled trial of the MoleMate
      system versus best practice (ISRCTN79932379) to estimate the expected long-term
      cost and health gain of diagnosis with the MoleMate system versus best practice
      in an English primary care setting. The model combines trial results with data
      from the wider literature to inform long-term prognosis, health state utilities,
      and cost. RESULTS: Results are reported as mean and incremental cost and quality
      adjusted life-years (QALYs) gained, incremental cost-effectiveness ratio with
      probabilistic sensitivity analysis, and value of information analysis. Over a
      lifetime horizon, the MoleMate system is expected to cost an extra L18 over best
      practice alone, and yield an extra 0.01 QALYs per patient examined. The
      incremental cost-effectiveness ratio is L1,896 per QALY gained, with a 66.1%
      probability of being below L30,000 per QALY gained. The expected value of perfect
      information is L43.1 million. CONCLUSIONS: Given typical thresholds in the United
      Kingdom (L20,000-L30,000 per QALY), the MoleMate system may be cost-effective
      compared with best practice diagnosis alone in a primary care setting. However,
      there is considerable decision uncertainty, driven particularly by the
      sensitivity and specificity of MoleMate versus best practice, and the risk of
      disease progression in undiagnosed melanoma; future research should focus on
      reducing uncertainty in these parameters.

PMID- 23538189
TI  - Quality of life in the first 6 weeks following laparoscopic and open colorectal
      surgery.
AB  - OBJECTIVES: Evidence of how health-related quality of life (HRQOL) changes
      following laparoscopic and open colorectal surgery in the first 6 weeks of
      postoperative recovery is needed to inform cost-effectiveness evaluations.
      METHODS: Pragmatic prospective cohort study design. Consecutive patients
      requiring elective colorectal surgery were allocated to either laparoscopic or
      open surgery by administrative staff in a district general hospital in England,
      2006-2007. Patients completed two validated, generic measures of HRQOL at
      baseline (preoperatively) and on multiple occasions in the first 6 weeks
      postsurgery using diaries (EuroQol five-dimensional [EQ-5D] questionnaire: 16
      times; short-form 36 health survey [SF-36]: 4 times; HRQOL was compared between
      groups at each time point, and overall using repeated-measures analysis. RESULTS:
      Of 201 consecutive patients recruited, 32 (15.1%) were unable to complete
      diaries. Of the remaining 169 patients, 120 (71%) returned completed diaries at
      28 days and 105 (62.1%) at 42 days. There was no difference in preoperative HRQOL
      scores between surgical groups, but the postoperative EQ-5D questionnaire and SF
      36 scores were significantly higher in the laparoscopic group (EQ-5D
      questionnaire P = 0.005, SF-36 P = 0.007). Subgroup analysis showed that patients
      with a stoma have worse HRQOL than those without. HRQOL did not differ between
      the laparoscopic and open stoma patients. CONCLUSIONS: This study presents unique
      prospective data demonstrating that laparoscopic surgery confers HRQOL benefits
      for patients in the early recovery period following colorectal surgery, compared
      with open surgery. Consideration of these data in the context of a cost
      effectiveness analysis will be reported separately.

PMID- 23538190
TI  - Predicting SF-6D from the European Organization for Treatment and Research of
      Cancer Quality of Life Questionnaire scores in patients with colorectal cancer.
AB  - OBJECTIVES: To develop a mapping model for estimating six-dimensional health
      state short form (SF-6D) utility scores from the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaires (QLQ-C30 and QLQ
      CR29) scores in patients with colorectal cancer (CRC), with and without
      adjustment for clinical and demographic characteristics. METHODS: Ordinary least
      squares regression models were applied to a cross-sectional data set of 216
      patients with CRC collected from a regional hospital in Hong Kong. Item responses
      or scale scores of cancer-specific (QLQ-C30) and colorectal-specific health
      related quality-of-life (QLQ-CR38/CR29) data and selected demographic and
      clinical characteristics of patients were used to predict the SF-6D scores. Model
      goodness of fit was examined by using exploratory power (R(2) and adjusted R(2)),
      Akaike information criterion, and Bayesian information criterion, and predictive
      performance was evaluated by using root mean square error, mean absolute error,
      and Spearman's correlation coefficients between predicted and observed SF-6D
      scores. Models were validated by using an independent data set of 56 patients
      with CRC. RESULTS: Both scale and item response models explained more than 67% of
      the variation in SF-6D scores. The best-performing model based on goodness of fit
      (R(2) = 75.02%), predictive ability in the estimation (root mean square error =
      0.080, mean absolute error = 0.065), and validation data set prediction (root
      mean square error = 0.103, mean absolute error = 0.081) included variables of
      main and interaction effects of the QLQ-C30 supplemented by QLQ-CR29 subset scale
      responses and a demographic (sex) variable. CONCLUSIONS: SF-6D scores can be
      predicted from QLQ-C30 and QLQ-CR38/CR29 scores with satisfactory precision in
      patients with CRC. The mapping model can be applied to QLQ-C30 and QLQ-CR38/CR29
      data sets to produce utility scores for the appraisal of clinical interventions
      targeting patients with CRC using economic evaluation.

PMID- 23538191
TI  - Patient preferences for biologic agents in rheumatoid arthritis: a discrete
      choice experiment.
AB  - OBJECTIVES: To assess patients' preferences for rheumatoid-arthritis treatments
      with biologic agents using a discrete-choice experiment. METHODS: A discrete
      choice experiment was conducted with adult rheumatoid-arthritis patients who had
      never been treated with biological agents from two university hospitals-public
      and private-in Buenos Aires, Argentina. We evaluated preferences for seven
      treatment attributes (with two to three levels each): effectiveness, mode of
      administration, frequency of administration, local and systemic adverse events,
      severe infections, and out-of-pocket costs.A probit regression model was used to
      analyze the relative importance of rheumatoid-arthritis treatment attributes. We
      estimated attributes' relative importance and their 95% confidence intervals.
      RESULTS: Survey responses from 240 patients with rheumatoid arthritis receiving
      conventional disease-modifying antirheumatic drugs were included in the study.
      All tested biological agents' attributes significantly affected the choice of
      treatment. Attributes' relative importance in decreasing order was the following
      (mean, confidence interval 95%): cost, 0.81 (0.69-0.92); systemic adverse events,
      0.66 (0.57-0.76); frequency of administration, 0.61 (0.52-0.71); efficacy, 0.42
      (0.32-0.51); route of administration, 0.41 (0.30-0.52); local adverse events,
      0.40 (0.31-0.49); and serious infections, 0.29 (0.22-0.37). CONCLUSIONS:
      Different treatment attributes had a significant and different influence in
      rheumatoid-arthritis patients' choice of biological agents. This type of study
      can not only inform about patients' preferences but also about the trade-offs
      among different possible treatments or process-related attributes.

PMID- 23538192
TI  - Mapping EQ-5D utility scores from the Incontinence Quality of Life Questionnaire
      among patients with neurogenic and idiopathic overactive bladder.
AB  - OBJECTIVES: To provide a mapping algorithm for estimating EuroQol five
      dimensional (EQ-5D) questionnaire index scores from the Incontinence-specific
      Quality of Life questionnaire (I-QOL) based on nationally representative samples
      of patients with idiopathic or neurogenic overactive bladder (OAB) using EQ-5D
      questionnaire preference valuations based on both the UK and US general
      populations. METHODS: Analyses were conducted for 2505 patients from the Adelphi
      Overactive Bladder Disease Specific Programme, a cross-sectional study of
      patients with idiopathic or neurogenic OAB, undertaken in the United States and
      Europe in 2010. A range of statistical modeling techniques was used. Tenfold
      cross-validation techniques were used to calculate mean absolute error (MAE) and
      root mean squared error (RMSE) goodness-of-fit statistics. Various predictor
      lists, together with a method combining stepwise selection with multivariable
      fractional polynomial techniques to allow nonlinear relationships to feature,
      were pursued. RESULTS: Choice of predictors was consistent for both the UK and US
      EQ-5D questionnaire tariffs. For idiopathic, the best model included the I-QOL
      total score and age (both modeled nonlinearly.) For neurogenic, the best model
      was the I-QOL social embarrassment domain score modeled linearly only. Best-fit
      results were better in the idiopathic (n = 2351; MAE = 0.10; RMSE = 0.14) than in
      the neurogenic sample (n = 254; MAE = 0.17; RMSE = 0.22). CONCLUSIONS: This
      research provides algorithms for mapping EQ-5D questionnaire index scores from
      the I-QOL, allowing calculation of appropriate preference-based health-related
      quality-of-life scores for use in cost-effectiveness analyses when only I-QOL
      data are available. The strongest results were for idiopathic patients, but those
      for neurogenic are consistent with those of other published mapping studies.

PMID- 23538193
TI  - Progression-free survival with fulvestrant 500 mg and alternative endocrine
      therapies as second-line treatment for advanced breast cancer: a network meta
      analysis with parametric survival models.
AB  - BACKGROUND: Ouwens et al. and Jansen have presented methods for (network) meta
      analysis of survival data by using a multidimensional treatment effect as an
      alternative to the synthesis of constant hazards ratios, which allow for a better
      fit to the data and the expected survival of competing interventions for cost
      effectiveness analysis. However, results may be sensitive to the assumed
      underlying survival function. OBJECTIVE: To estimate the expected progression
      free survival (PFS) for fulvestrant 500 mg versus alternative hormonal therapies
      for postmenopausal women with advanced breast cancer who relapsed previously by
      means of a network meta-analysis of currently available randomized controlled
      trials using alternative underlying survival functions. METHODS: Eleven
      randomized controlled trials were included that evaluated fulvestrant 500 mg (n =
      3), fulvestrant 250 mg (n = 5), fulvestrant 250 mg loading dose (n = 3),
      anastrozole 1 mg (n = 3), megestrol acetate (n = 4), letrozole 2.5 mg (n = 3),
      letrozole 0.5 mg (n = 3), and exemestane (n = 2). PFS percentages and numbers at
      risk were derived from Kaplan-Meier curves and combined by means of Bayesian
      network meta-analysis on the basis of the difference in the shape and scale
      parameters of the Weibull, log-normal, and log-logistic parametric survival
      functions. RESULTS: The log-normal distribution provided the best fit, suggesting
      that the proportional hazard assumption was not valid. Based on the difference in
      expected PFS, it was found that fulvestrant 500 mg is more efficacious than
      fulvestrant 250 mg, megestrol acetate, and anastrozole (-5.73 months; 95%
      credible interval [CrI]-10.67,-1.67). Expected PFS for fulvestrant 500 mg ranged
      from 10.87 (95% CrI 9.21, 13.07) to 17.02 (95% CrI 13.33, 22.02) months for the
      Weibull versus log-logistic distribution. CONCLUSIONS: Fulvestrant 500 mg is
      expected to be more efficacious than fulvestrant 250 mg, megestrol acetate, and
      anastrozole 1 mg and at least as efficacious as exemestane and letrozole 2.5 mg
      in terms of PFS among postmenopausal women with advanced breast cancer after
      failure on endocrine therapy. The findings were not sensitive to the
      distribution, although the expected PFS varied substantially, emphasizing the
      importance of performing sensitivity analyses.

PMID- 23538194
TI  - Comparative incidence and health care costs of medically attended adverse effects
      among U.S. Medicaid HIV patients on atazanavir- or darunavir-based antiretroviral
      therapy.
AB  - OBJECTIVES: This is the first study to compare the incidence and health care
      costs of medically attended adverse effects in atazanavir- and darunavir-based
      antiretroviral therapy (ART) among U.S. Medicaid patients receiving routine HIV
      care. METHODS: This was a retrospective study using Medicaid administrative
      health care claims from 15 states. Subjects were HIV patients aged 18 to 64 years
      initiating atazanavir- or darunavir-based ART from January 1, 2003, to July 1,
      2010, with continuous enrollment for 6 months before (baseline) and 6 months
      after (evaluation period) ART initiation and 1 or more evaluation period medical
      claim. Outcomes were incidence and health care costs of the following medically
      attended (International Classification of Diseases, Ninth Revision, Clinical
      Modification-coded or treated) adverse effects during the evaluation period:
      gastrointestinal, lipid abnormalities, diabetes/hyperglycemia, rash, and
      jaundice. All-cause health care costs were also determined. Patients treated with
      atazanavir and darunavir were propensity score matched (ratio = 3:1) by using
      demographic and clinical covariates. Multivariable models adjusted for covariates
      lacking postmatch statistical balance. RESULTS: Propensity-matched study sample
      included 1848 atazanavir- and 616 darunavir-treated patients (mean age 41 years,
      50% women, 69% black). Multivariable-adjusted hazard ratios (HRs) (for darunavir,
      reference = atazanavir) and per-patient-per-month health care cost differences
      (darunavir minus atazanavir) were as follows: gastrointestinal, HR = 1.25 (P =
      0.04), $43 (P = 0.13); lipid abnormalities, HR = 1.38 (P = 0.07), $3 (P = 0.88);
      diabetes/hyperglycemia, HR = 0.84 (P = 0.55), $13 (P = 0.69); and rash, HR = 1.11
      (P = 0.23), $0 (P = 0.76); all-cause health care costs were $1086 (P<0.001). Too
      few instances of jaundice (11 in atazanavir and 1 in darunavir) occurred to
      support multivariable modeling. CONCLUSIONS: Medication tolerability can be
      critical to the success or failure of ART. Compared with darunavir-treated
      patients, atazanavir-treated patients had significantly fewer instances of
      medically attended gastrointestinal issues and more instances of jaundice and
      incurred significantly lower health care costs.

PMID- 23538195
TI  - Assessing the determinants of the potential for cost-effectiveness over time: the
      empirical case of COPD.
AB  - OBJECTIVES: The objective of this study was to assess the potential for cost
      effectiveness of new technologies for chronic obstructive pulmonary disease
      (COPD) over the period from 2001 to 2010. METHODS: Lung function outcomes and
      drug prices were observed for a UK COPD population over the period from 2001 to
      2010. Cost-effectiveness was assessed at regular intervals on the basis of an
      established cost-effectiveness model, and the maximum price a technology
      providing cure could achieve under the current cost-effectiveness rules was
      estimated. RESULTS: The results of this study show that although the scope for
      clinical improvement in COPD was still considerable, during the 10 years studied,
      the potential for cost-effectiveness at each point in time was dependent on
      momentary market characteristics, such as the changing price of comparators and
      improvements in clinical effectiveness. As a result, the analysis demonstrates
      that the future cost-effectiveness of a technology in development depends on the
      manner pricing and clinical effectiveness evolve throughout time. CONCLUSIONS:
      Because any predictions will be short-lived and dependent on a number of
      uncertain factors, we conclude that producing accurate forecasts on the potential
      for cost-effectiveness of new therapies earlier during the development process is
      especially difficult under the current static cost-effectiveness framework.

PMID- 23538196
TI  - An expert on every street corner? Methods for eliciting distributions in
      geographically dispersed opinion pools.
AB  - Recent publications outline developments in eliciting probabilistic opinions from
      clinical experts with which to inform structural assumptions and parameter
      estimates in health economic models. We outline approaches taken to date to
      elicit probabilistic distributions from experts within the health economic
      literature and outline the appropriate considerations and the resulting process
      in developing a new elicitation program with the aim of allowing low-cost
      elicitation of expert opinion from a heterogeneous and geographically dispersed
      opinion pool while preserving the essential features of good practice elicitation
      methods.

PMID- 23538197
TI  - Need for speed: an efficient algorithm for calculation of single-parameter
      expected value of partial perfect information.
AB  - BACKGROUND: The expected value of partial perfect information (EVPPI) is a
      theoretically justifiable and informative measure of uncertainty in decision
      analytic cost-effectiveness models, but its calculation is computationally
      intensive because it generally requires two-level Monte Carlo simulation. We
      introduce an efficient, one-level simulation method for the calculation of single
      parameter EVPPI. OBJECTIVE: We show that under mild regularity assumptions, the
      expectation-maximization-expectation sequence in EVPPI calculation can be
      transformed into an expectation-maximization-maximization sequence. By doing so,
      calculations can be performed in a single-step expectation by using data
      generated for probabilistic sensitivity analysis. We prove that the proposed
      estimator of EVPPI converges in probability to the true EVPPI. METHODS AND
      RESULTS: The performance of the new method was empirically demonstrated by using
      three exemplary decision models. Our proposed method seems to achieve remarkably
      higher accuracy than the two-level method with a fraction of its computation
      costs, though the achievement in accuracy was not uniform and varied across the
      parameters of the models. Software is provided to calculate single-parameter
      EVPPI based on the probabilistic sensitivity analysis data. CONCLUSIONS: The new
      method, though applicable only to single-parameter EVPPI, is fast, accurate, and
      easy to implement. Further research is needed to evaluate the performance of this
      method in more complex scenarios and to extend such a concept to similar measures
      of decision uncertainty.

PMID- 23538198
TI  - Evidence synthesis assumes additivity on the scale of measurement: response to
      "Rank reversal in indirect comparisons" by Norton et al.

PMID- 23538199
TI  - Response about rank reversal.

PMID- 23538200
TI  - Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.
AB  - Economic evaluations of health interventions pose a particular challenge for
      reporting. There is also a need to consolidate and update existing guidelines and
      promote their use in a user friendly manner. The Consolidated Health Economic
      Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate
      and update previous health economic evaluation guidelines efforts into one
      current, useful reporting guidance. The primary audiences for the CHEERS
      statement are researchers reporting economic evaluations and the editors and peer
      reviewers assessing them for publication. The need for new reporting guidance was
      identified by a survey of medical editors. A list of possible items based on a
      systematic review was created. A two round, modified Delphi panel consisting of
      representatives from academia, clinical practice, industry, government, and the
      editorial community was conducted. Out of 44 candidate items, 24 items and
      accompanying recommendations were developed. The recommendations are contained in
      a user friendly, 24 item checklist. A copy of the statement, accompanying
      checklist, and this report can be found on the ISPOR Health Economic Evaluations
      Publication Guidelines Task Force website:
      (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to
      better reporting, and ultimately, better health decisions. To facilitate
      dissemination and uptake, the CHEERS statement is being co-published across 10
      health economics and medical journals. We encourage other journals and groups, to
      endorse CHEERS. The author team plans to review the checklist for an update in
      five years.

PMID- 23538201
TI  - Ezetimibe increases hepatic iron levels in mice fed a high-fat diet.
AB  - Accumulating evidence suggests that ezetimibe may be a promising agent for
      treatment of nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH).
      Phlebotomy and dietary iron restriction reduce serum transaminase in NAFLD/NASH
      patients. Recent studies have shown that a mutual effect exists between lipid
      metabolism and iron metabolism. Accordingly, we examined the effect of ezetimibe
      on iron metabolism in mice fed a high-fat diet with or without iron. We fed
      C57BL/6 mice the following diets for 12 weeks. Experiment 1 comprised [1] a
      control diet (C), [2] C plus ezetimibe (0.3 mg/day; 4 weeks) (CE), [3] a high-fat
      diet (H), and [4] H plus ezetimibe (HE). Experiment 2 comprised [1] C containing
      carbonyl iron (average; 22.4 mg/day; 6 weeks) (CI), [2] CI plus ezetimibe (CIE),
      [3] H containing carbonyl iron (HI), and [4] HI plus ezetimibe (HIE). Blood,
      livers, and duodenum were removed after 12 weeks. In experiment 1, the hepatic
      iron levels were higher in HE than H, whereas there was no difference between C
      and CE. Hepatic mRNA expression of transferrin receptor 1 and 2, ferritins, and
      hepcidin were increased more in CE than C, and more in HE than H. In the
      duodenum, divalent metal transporter 1, ferritin H, and hephaestin mRNA levels
      were increased in CE compared with C. In experiment 2, hepatic iron
      concentrations were higher in HIE than HI. Hepatic mRNA expression of ferritin L
      and hepcidin were increased in HIE compared with HI. In duodenum, ferritin L mRNA
      was increased in HIE compared with CIE. Ezetimibe induced hepatic iron uptake
      transporter expression in mice fed a high-fat diet, causing increased hepatic
      iron concentrations.

PMID- 23538202
TI  - Metabolic and cellular organization in evolutionarily diverse microalgae as
      related to biofuels production.
AB  - Microalgae are among the most diverse organisms on the planet, and as a result of
      symbioses and evolutionary selection, the configuration of core metabolic
      networks is highly varied across distinct algal classes. The differences in
      photosynthesis, carbon fixation and processing, carbon storage, and the
      compartmentation of cellular and metabolic processes are substantial and likely
      to transcend into the efficiency of various steps involved in biofuel molecule
      production. By highlighting these differences, we hope to provide a framework for
      comparative analyses to determine the efficiency of the different arrangements or
      processes. This sets the stage for optimization on the based on information
      derived from evolutionary selection to diverse algal classes and to synthetic
      systems.

PMID- 23538203
TI  - Immunization of mice with a newly identified thyroid-stimulating hormone receptor
      splice variant induces Graves'-like disease.
AB  - We have cloned a thyroid-stimulating hormone receptor (TSHR) cDNA from mouse
      thyroid glands. The sequence of this cDNA indicated that it encoded a 739 amino
      acid TSHR splice variant that lacked exon 5 (TSHR739). In thyroid gland samples
      from adult mice, the amount of TSHR739 mRNA was about 10% of the amount of full
      length TSHR (TSHR764) mRNA. A eCFP-tagged TSHR739 integrated into plasma
      membrane, but lacked TSH binding activity and it did not produce cAMP in response
      to TSH. However, thyroid-stimulating antibodies from patients with Graves'
      disease stimulated cAMP production in HEK293 cells that expressed TSHR739.
      Quantitative PCR revealed that TSHR739 transcript levels were low in the fetal
      mouse thyroid samples, but TSHR739 transcript levels increased after birth and as
      the mice grew. We used plasmid injection combined with electroporation into
      skeletal muscles to immunize BALB/c mice with TSHR739, TSHR764,, or control
      plasmid; TSHR739 caused goiters, high (125)I uptake activity, thyrotoxicosis, and
      production of thyroid-stimulating antibodies, but TSHR764, or control did not.
      These results indicated that immunization with an autologous TSHR antigen,
      TSHR739, induced Graves'-like disease in mice, and that TSHR739 is a candidate
      autoantigen in autoimmune thyroid disease.

PMID- 23538204
TI  - Bioethics and religious bodies: refusal of blood transfusions in Germany.
AB  - The refusal of medical treatment is a recurrent topic in bioethical debates and
      Jehovah's Witnesses often constitute an exemplary case in this regard. The
      refusal of a potentially life-saving blood transfusion is a controversial choice
      that challenges the basic medical principle of acting in patients' best interests
      and often leads physicians to adopt paternalistic attitudes toward patients who
      refuse transfusion. However, neither existing bioethical nor historical and
      social sciences scholarship sufficiently addresses experiences of rank-and-file
      Witnesses in their dealings with the health care system. This article draws on
      results of a nine-month (2010, 2011-2012) ethnographic research on the
      relationship between religious, legal, ethical, and emotional issues emerging
      from the refusal of blood transfusions by Jehovah's Witnesses in Germany (mainly
      in Berlin). It shows how bioethical challenges are solved in practice by some
      German physicians and what they perceive to be the main goal of biomedicine:
      promoting the health or broadly understood well-being of patients. I argue that
      two different understandings of the concept of autonomy are at work here:
      autonomy based on reason and autonomy based on choice. The first is privileged by
      German physicians in line with a Kantian philosophical tradition and
      constitutional law; the second, paradoxically, is utilized by Jehovah's Witnesses
      in their version of the Anglo-Saxon Millian approach.

PMID- 23538205
TI  - In vitro assessment of functional properties of lactic acid bacteria isolated
      from faecal microbiota of healthy dogs for potential use as probiotics.
AB  - Lactic acid bacteria were isolated and identified in the faeces of Chinese
      Crested and Yorkshire terrier pups and their probiotic features were investigated
      in vitro. Thirty seven isolates were identified as Lactobacillus or Enterococcus.
      Out of these isolates, 31 were lactic acid bacteria (LAB) and belonged to the
      species Lactobacillus reuteri (16/37; 43.3%), Lactobacillus animalis (7/37;
      18.9%), Lactobacillus acidophilus (3/37; 8.1%), Lactobacillus sanfranciscensis
      (2/37; 5.4%), Lactobacillus murinus (2/37; 5.4%), and Lactobacillus paraplantarum
      (1/37; 2.7%), while six other LAB isolates were Enterococcus spp. (6/37; 16.2%).
      Strains were tested for resistance to gastric acidity (pH 2.5 for 3 h) and bile
      salts (0.3% ox gall), cell surface hydrophobicity by microbial adhesion to
      solvents, antagonism against pathogenic bacteria (Staphylococcus aureus,
      Enterococcus faecalis, Bacillus cereus, Pseudomonas aeruginosa, Escherichia coli,
      Salmonella enterica serovar Typhimurium and Listeria monocytogenes), production
      of hydrogen peroxide, and antibiotic susceptibility. Thirty four strains were
      highly resistant to acidic conditions with slight (18 strains) to moderate (16
      strains) growth inhibition by bile salts. Seven isolates had highly hydrophobic
      cellular surfaces and 28 strains exhibited strong antagonism against the
      bacterial pathogens tested, although 8 isolates tested against Leptospira
      interrogans had no effect on pathogen growth. All isolates produced low rates of
      hydrogen peroxide. Based on these results, two Lactobacillus strains showed
      promising probiotic-related features and merit investigation as probiotics for
      dogs. 

PMID- 23538207
TI  - A non-equilibrium neutral model for analysing cultural change.
AB  - Neutral evolution is a frequently used model to analyse changes in frequencies of
      cultural variants over time. Variants are chosen to be copied according to their
      relative frequency and new variants are introduced by a process of random
      mutation. Here we present a non-equilibrium neutral model which accounts for
      temporally varying population sizes and mutation rates and makes it possible to
      analyse the cultural system under consideration at any point in time. This
      framework gives an indication whether observed changes in the frequency
      distributions of a set of cultural variants between two time points are
      consistent with the random copying hypothesis. We find that the likelihood of the
      existence of the observed assemblage at the end of the considered time period
      (expressed by the probability of the observed number of cultural variants present
      in the population during the whole period under neutral evolution) is a powerful
      indicator of departures from neutrality. Further, we study the effects of
      frequency-dependent selection on the evolutionary trajectories and present a case
      study of change in the decoration of pottery in early Neolithic Central Europe.
      Based on the framework developed we show that neutral evolution is not an
      adequate description of the observed changes in frequency.

PMID- 23538206
TI  - Physical dependence on gamma-hydroxybutrate (GHB) prodrug 1,4-butanediol (1,4
      BD): time course and severity of withdrawal in baboons.
AB  - BACKGROUND: 1,4-Butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) pro-drug,
      with multiple commercial uses, and a drug of abuse. Although there are case
      reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated
      the physical dependence potential of 1,4-BD and characterized the time course of
      withdrawal. METHODS: Vehicle and then 1,4-BD were administered continuously 24
      h/day via intragastric catheters in male baboons (Papio anubis, n=3). Dosing was
      initiated at 100 mg/kg and increased by 100mg/kg/day to 400mg/kg. After a
      stabilization period, doses of 500 and then 600 mg/kg/day were each maintained
      for 3-4 weeks. Plasma levels of 1,4-BD and GHB were determined for each dose
      condition. Physical dependence was assessed via administration of a GABA-B
      antagonist (precipitated withdrawal test) during administration of the 600 mg/kg
      dose and via abrupt termination of chronic 1,4-BD administration (spontaneous
      withdrawal test). Outcome measures included the number of food pellets earned,
      performance on a fine-motor task, observed behaviors, and plasma levels of GHB
      and 1,4-BD. RESULTS: Following maintenance of 1,4-BD 600 mg/kg for 3 weeks, the
      number of food pellets earned was significantly decreased. At the end of chronic
      1,4-BD dosing, the levels of GHB in plasma ranged from 1290 to 2300 MUmol/L and
      levels of 1,4-BD in plasma ranged from 13.1 to 37.9 MUmol/L. Signs of physical
      dependence were observed following precipitated and spontaneous withdrawal tests.
      Seizures were not observed. CONCLUSIONS: These data indicate chronic 1,4-BD
      produced physical dependence in baboons and the withdrawal syndrome can be
      characterized as mild to intermediate.

PMID- 23538208
TI  - Long-term measurement of impedance in chronically implanted depth and subdural
      electrodes during responsive neurostimulation in humans.
AB  - Long-term stability of the electrode-tissue interface may be required to maintain
      optimal neural recording with subdural and deep brain implants and to permit
      appropriate delivery of neuromodulation therapy. Although short-term changes in
      impedance at the electrode-tissue interface are known to occur, long-term changes
      in impedance have not previously been examined in detail in humans. To provide
      further information about short- and long-term impedance changes in chronically
      implanted electrodes, a dataset from 191 persons with medically intractable
      epilepsy participating in a trial of an investigational responsive
      neurostimulation device (the RNS((r)) System, NeuroPace, Inc.) was reviewed.
      Monopolar impedance measurements were available for 391 depth and subdural leads
      containing a total of 1564 electrodes; measurements were available for median 802
      days post-implant (range 28-1634). Although there were statistically significant
      short-term impedance changes, long-term impedance was stable after one year.
      Impedances for depth electrodes transiently increased during the third week after
      lead implantation and impedances for subdural electrodes increased over 12 weeks
      post-implant, then were stable over the subsequent long-term follow-up. Both
      depth and subdural electrode impedances demonstrated long-term stability,
      suggesting that the quality of long-term electrographic recordings (the data used
      to control responsive brain stimulation) can be maintained over time. 

PMID- 23538209
TI  - The effect of ghrelin on MK-801 induced memory impairment in rats.
AB  - Accumulating evidence indicates that the brain-gut peptide ghrelin which is
      expressed in hippocampus improves memory and learning processes. The MK-801, a
      noncompetitive NMDA receptor antagonist, has also shown amnesic properties in
      animal model. The current study was to find out whether intracerebroventricular
      administration of ghrelin can prevent amnesia induced by MK-801 in rats. A week
      after the surgery, during which cannuals were implanted in the lateral
      ventricular, the animals were trained and tested in a step-through type passive
      avoidance task. Memory retrieval was measured by step-through latency (STL) and
      total time in dark compartments (TDC). In the first series of experiments, we
      established a dose-response relationship for ghrelin on the passive avoidance
      paradigm. In the second set of experiments, animals were divided to two groups.
      In the first group, MK-801 (0.075, 0.15 and 0.3mg/kg) was injected
      intraperitoneally (i.p.) immediately after the acquisition session and in the
      second group MK-801 (same doses) was injected (i.p.) 30 min before the retention
      session. Analysis of data showed that in both groups, MK-801 impaired learning
      and memory. In the third set of experiments, administration of ghrelin (200
      ng/rat) right after the acquisition session (i.e. before MK-801 injection)
      improved the MK-801 induced memory impairment, but administration of ghrelin
      before retrieval session did not affect the MK-801 induced memory impairment.
      These results show an interaction between ghrelin and glutamatergic system. A
      novel finding in this study is that ghrelin can prevent amnesia produced by NMDA
      antagonist in rats when injected in post-training phase.

PMID- 23538210
TI  - CRHR1 mediates p53 transcription induced by high altitude hypoxia through ERK 1/2
      signaling in rat hepatic cells.
AB  - We have previously reported that hypoxia activates corticotrophin-releasing
      hormone (CRH) and the expression of its type-1 receptor (CRHR1) and induces
      disorders of the brain-endocrine-immune network. p53 is activated by hypoxia and
      involved in tumorigenesis and apoptosis. Whether CRHR1 regulates p53
      transactivation to further influence apoptotic genes remains unclear. Here, we
      showed that hypoxia at a simulated altitude of 5km or 7km for 8 and 24h increased
      p53 protein and mRNA, and reduced apoptotic bax and IGFBP3 gene expression while
      upregulating the cell-arrest gene p21 for 8h in rat liver cells. The upregulation
      of p53 mRNA and downregulation of bax mRNA induced by hypoxia were blocked by
      pretreatment with the specific CRHR1 antagonist CP-154,526, but the
      downregulation of IGFBP3 and upregulation of p21 mRNA were not. Furthermore, CRH
      stimulated p53 mRNA via the ERK 1/2 pathway in the BRL-3A cell line and this was
      blocked by the ERK 1/2 antagonist U0126. These data provide novel evidence that
      the CRHR1-triggered ERK 1/2 pathway is involved in the activation of p53 and
      suppression of the apoptotic bax gene by hypoxia in rat liver.

PMID- 23538211
TI  - Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression
      in the dorsal medulla of adult sheep.
AB  - Glucocorticoids including betamethasone (BM) are routinely administered to women
      entering into early preterm labor to facilitate fetal lung development and
      decrease infant mortality; however, fetal steroid exposure may lead to
      deleterious long term consequences. In a sheep model of fetal programming, BM
      exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and
      decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of
      age associated with changes in the circulating and renal renin-angiotensin
      systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions
      through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas
      receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen
      (Aogen), and receptor expression in this brain region of exposed and control
      offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly
      lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1
      receptor expression was not changed. BMX offspring exhibited a higher ratio of
      Ang II to Ang-(1-7) (2.30+/-0.36 versus 0.99+/-0.28; p<0.01) and Ang II to Ang I
      at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in
      0.5-year BMX animals (0.78+/-0.06 vs. 1.94+/-0.41; p<0.05) suggesting a greater
      degree of enzymatic processing of the precursor protein in exposed animals. We
      conclude that in utero BM exposure promotes an imbalance in the central RAS
      pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and
      lower BRS in this model.

PMID- 23538212
TI  - Orexigenic effects of omentin-1 related to decreased CART and CRH gene expression
      and increased norepinephrine synthesis and release in the hypothalamus.
AB  - Omentin-1, a visceral fat depot-specific secretory protein, is inversely
      correlated with obesity and insulin resistance. We investigated, in rats, the
      effects of chronic omentin-1 administration (8 MUg/kg, intraperitoneally, once
      daily for 14-days) on feeding behavior and related hypothalamic peptides and
      neurotransmitters. Food intake and body weight were recorded daily throughout the
      study. We found a significantly increased food intake compared to controls, but
      only in days 10-14, while body weight significantly increased since day 12
      (P<0.05). Compared with vehicle, omentin-1 treatment led to a significant
      reduction in both cocaine and amphetamine-regulated transcript (CART) (P<0.05)
      and corticotrophin releasing hormone (CRH) (P<0.05) gene expression, while pro
      opiomelanocortin (POMC), agouti-related peptide (AgRP), neuropeptide Y (NPY) and
      orexin-A gene expression were not modified with respect to vehicle-treated rats.
      We also found an increase in hypothalamic levodopa (l-dopa) (P<0.05) and
      norepinephrine (NE) (P<0.01) synthesis, without any effect on dopamine (DA) and
      serotonin (5-hydroxytryptamine, 5-HT) metabolism. Furthermore, in hypothalamic
      synaptosomes, omentin-1 (10-100 ng/ml) stimulated basal NE release (ANOVA,
      P<0.0001; post hoc, P<0.001 vs. vehicle), in a dose-dependent manner, leaving
      unaffected both basal and depolarization-induced DA and 5-HT release. Finally,
      when synaptosomes were co-perfused with leptin and omentin-1, we observed that
      leptin was able to reverse omentin-1-induced stimulation of NE. In conclusion,
      the orexigenic effects of omentin-1 could be related, at least in part, to
      decreased CART and CRH gene expression and increased NE synthesis and release in
      the hypothalamus.

PMID- 23538213
TI  - Neuromedin U causes biphasic cardiovascular effects and impairs baroreflex
      function in rostral ventrolateral medulla of spontaneously hypertensive rat.
AB  - Neuromedin U (NMU) causes biphasic cardiovascular and sympathetic responses and
      attenuates adaptive reflexes in the rostral ventrolateral medulla (RVLM) and
      spinal cord in normotensive animal. However, the role of NMU in the pathogenesis
      of hypertension is unknown. The effect of NMU on baseline cardiorespiratory
      variables in the RVLM and spinal cord were investigated in urethane
      anaesthetized, vagotomized and artificially ventilated male spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Experiments were also
      conducted to determine the effects of NMU on somatosympathetic and baroreceptor
      reflexes in the RVLM of SHR and WKY. NMU injected into the RVLM and spinal cord
      elicited biphasic response, a brief pressor and sympathoexcitatory response
      followed by a prolonged depressor and sympathoinhibitory response in both
      hypertensive and normotensive rat models. The pressor, sympathoexcitatory and
      sympathoinhibitory responses evoked by NMU were exaggerated in SHR. Phrenic nerve
      amplitude was also increased following intrathecal or microinjection of NMU into
      the RVLM of both strains. NMU injection into the RVLM attenuated the
      somatosympathetic reflex in both SHR and WKY. Baroreflex sensitivity was impaired
      in SHR at baseline and further impaired following NMU injection into the RVLM.
      NMU did not affect baroreflex activity in WKY. The present study provides
      functional evidence that NMU can have an important effect on the cardiovascular
      and reflex responses that are integrated in the RVLM and spinal cord. A role for
      NMU in the development and maintenance of essential hypertension remains to be
      determined.

PMID- 23538214
TI  - Transverse stability of the proximal segment after bilateral sagittal split ramus
      osteotomy for mandibular setback surgery.
AB  - This study aimed to evaluate the correlation between the transverse displacement
      of the proximal segment after bilateral sagittal osteotomy for mandibular setback
      and the amount and design of the mandibular setback. Patients who underwent
      either bilateral sagittal split ramus osteotomy (BSSRO) alone or two-jaw surgery
      were selected, and cephalographic postero-anterior (PA) measurements were taken
      pre-operatively (T1), immediately post-operatively (T2), and at follow-up (T3).
      The inter-gonal (IG) and inter-ramal (IR) width increased immediately after
      surgery, but decreased to the initial value during follow-up (P=0.002; IR,
      P=0.046). Only the immediate IG changes after surgery correlated with the amount
      of mandibular setback (P=0.009). The IG changes were significant in the symmetric
      group, but not in the asymmetric group. There was no difference in the IG and IR
      changes between the symmetric group and the asymmetric group. The immediate IG
      change in two-jaw patients with symmetric setback showed correlation with the
      setback amount. The gonial width of the deviated group showed more significant
      changes than that of the non-deviated group. There was no difference in the
      unilateral gonial width between the deviated and the non-deviated group, but the
      difference was significant for the unilateral ramal angle between the two groups.
      These correlations will be helpful in predicting post-surgical results for
      patients.

PMID- 23538215
TI  - Botulinum toxin injection for management of temporomandibular joint clicking.
AB  - The aim of the present study was to investigate the effect of botulinum toxin
      type A (BTX-A) injection in the lateral pterygoid (LP) muscle on
      temporomandibular joint (TMJ) clicking. The study enrolled seven patients with a
      total of 11 joints; all patients were stage I or II of Wilke's staging for
      internal derangement. BTX-A was injected in the ipsilateral LP muscle with
      electromyogram (EMG) guidance and the subjects were assessed for 4 months.
      Maximum inter-incisal opening, range of lateral movement, and the presence of a
      click were recorded throughout the follow-up period, and magnetic resonance
      imaging (MRI) was ordered at the end of the 4 months. The results showed that the
      decrease in inter-incisal opening and side to side movement immediately
      postoperative was statistically significant, while the difference by the end of
      the follow-up period was insignificant. MRI showed a marked improvement in disc
      position postoperatively. It may be concluded that BTX injection in the LP muscle
      leads to the disappearance of joint clicking clinically and a significant
      improvement in disc position as shown on MRI.

PMID- 23538217
TI  - Two birds with one stone.

PMID- 23538216
TI  - Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with
      metastatic breast cancer.
AB  - BACKGROUND: Enumeration of circulating tumor cells (CTC) from whole blood permits
      monitoring of patients with breast carcinoma. Analysis of apoptosis & Bcl-2
      expression in CTC might add additional prognostic and predictive information. We
      estimated the degree of these markers in CTC from patients being treated for
      metastatic breast cancer. METHODS: Eighty-three evaluable patients initiating a
      new therapy for metastatic breast cancer were enrolled. Whole blood was collected
      at baseline, at one of three short term time windows (24, 48, or 72 h) after
      initiating treatment, and at first follow-up (3-5 weeks). CTC were isolated,
      enumerated, and expression of M30 and Bcl2 was determined using the
      CellSearch((r)) System. RESULTS: At baseline, window, and 3-5 weeks post
      treatment, 41/80 (51%), 40/80 (50%) and 21/75 (28%) patients had >=5 CTC,
      respectively. At baseline, the proportion of CTC-apoptosis (M30) was inversely
      correlated with CTC number, and modestly inversely correlated with CTC-Bcl-2. As
      expected, higher CTC levels at baseline or first follow-up were associated with
      worse prognosis. Surprisingly, in patients with elevated CTC, higher levels of
      CTC-apoptosis were associated with worse prognosis, while higher CTC-Bcl-2 levels
      correlated with better outcomes. CONCLUSIONS: CTC apoptosis and expression of Bcl
      2 can be analytically determined in patients with metastatic breast cancer and
      may have biological and clinical implications. Characterization of CTC for these
      and other markers could further increase the utility of CTC monitoring patients
      in clinical investigations of new anti-neoplastic agents.

PMID- 23538218
TI  - Chasing Koch's chimera.

PMID- 23538219
TI  - Weighing for results: assessing the effect of IPTp - authors' reply.

PMID- 23538220
TI  - Weighing for results: assessing the effect of IPTp.

PMID- 23538221
TI  - US Department of Defense contributions to malaria surveillance.

PMID- 23538222
TI  - Ultrasonography in diagnosis of pulmonary hydatid cysts.

PMID- 23538223
TI  - Surviving sepsis in an intermediate care unit.

PMID- 23538224
TI  - Development of sympathetic cardiovascular control in embryonic, hatchling, and
      yearling female American alligator (Alligator mississippiensis).
AB  - We used arterial tyramine injections to study development of sympathetic actions
      on in vivo heart rate and blood pressure in embryonic, hatching and yearling
      female American alligators. Tyramine is a pharmacological tool for understanding
      comparative and developmental sympathetic regulation of cardiovascular function,
      and this indirect sympathomimetic agent causes endogenous neuronal catecholamine
      release, increasing blood pressure and heart rate. Arterial tyramine injection in
      hatchling and yearling alligators caused the typical vertebrate response - rise
      in heart rate and blood pressure. However, in embryonic alligators, tyramine
      caused a substantial and immediate bradycardia at both 70% and 90% of embryonic
      development. This embryonic bradycardia was accompanied by hypotension, followed
      by a sustained hypertension similar to the hatchling and juvenile responses.
      Pretreatment with atropine injection (cholinergic receptor blocker) eliminated
      the embryonic hypotensive bradycardia, and phentolamine pretreatment (alpha
      adrenergic receptor blocker) eliminated the embryonic hypotensive and
      hypertensive responses but not the bradycardia. In addition, hexamethonium
      pretreatment (nicotinic receptor blocker) significantly blunted embryos'
      bradycardic tyramine response. However, pretreatment with 6-hydroxydopamine, a
      neurotoxin that destroys catecholaminergic terminals, did not eliminate the
      embryonic bradycardia. Tyramine likely stimulated a unique embryonic response -
      neurotransmitter release from preganglionic nerve terminals (blocked with
      hexamethonium) and an acetylcholine mediated bradycardia with a secondary
      norepinephrine-dependent sustained hypertension. In addition, tyramine appears to
      stimulate sympathetic nerve terminals directly, which contributed to the overall
      hypertension in the embryonic, hatchling and yearling animals. Data demonstrated
      that humoral catecholamine control of cardiovascular function was dominant over
      the immature parasympathetic nervous system in developing alligator embryos, and
      suggested that sympathetic and parasympathetic nerve terminals were present and
      developing in ovo but were not tonically active.

PMID- 23538225
TI  - Role of brain nitric oxide in the cardiovascular control of bullfrogs.
AB  - The goal of the present study was to determine if nitric oxide (NO) acting on the
      brain of bullfrog (Lithobates catesbeianus) is involved in arterial pressure and
      heart rate (HR) control by influencing sympathetic activity. We investigated the
      effect of intracerebroventricular injections of L-NMMA (a nonselective NO
      synthase inhibitor) on mean arterial blood pressure (MAP), HR and cutaneous
      vascular conductance (CVC) of pelvic skin after intravenous injection of alpha or
      beta adrenergic blockers, prazosin or sotalol, respectively. Arterial pressure
      was directly measured by a telemetry sensor inserted in the aortic arch of
      animals. L-NMMA increased MAP, but did not change HR. This hypertensive response
      was inhibited by the pre-treatment with prazosin, but accentuated by sotalol. The
      effect of L-NMMA on MAP was also inhibited by i.v. injections of the ganglionic
      blocker, hexamethonium. Thus, NO acting on the brain of bullfrog seems to present
      a hypotensive effect influencing the sympathetic activity dependent on alpha and
      beta adrenergic receptors in the periphery.

PMID- 23538226
TI  - The effect of proteasome inhibition on the generation of the human leukocyte
      antigen (HLA) peptidome.
AB  - The Major histocompatibility complex (MHC) class I peptidome is thought to be
      generated mostly through proteasomal degradation of cellular proteins, a notion
      that is based on the alterations in presentation of selected peptides following
      proteasome inhibition. We evaluated the effects of proteasome inhibitors,
      epoxomicin and bortezomib, on human cultured cancer cells. Because the inhibitors
      did not reduce the level of presentation of the cell surface human leukocyte
      antigen (HLA) molecules, we followed their effects on the rates of synthesis of
      both HLA peptidome and proteome of the cells, using dynamic stable isotope
      labeling in tissue culture (dynamic-SILAC). The inhibitors reduced the rates of
      synthesis of most cellular proteins and HLA peptides, yet the synthesis rates of
      some of the proteins and HLA peptides was not decreased by the inhibitors and of
      some even increased. Therefore, we concluded that the inhibitors affected the
      production of the HLA peptidome in a complex manner, including modulation of the
      synthesis rates of the source proteins of the HLA peptides, in addition to their
      effect on their degradation. The collected data may suggest that the current
      reliance on proteasome inhibition may overestimate the centrality of the
      proteasome in the generation of the MHC peptidome. It is therefore suggested that
      the relative contribution of the proteasomal and nonproteasomal pathways to the
      production of the MHC peptidome should be revaluated in accordance with the
      inhibitors effects on the synthesis rates of the source proteins of the MHC
      peptides. 

PMID- 23538227
TI  - The MYDas touch of next-gen sequencing.

PMID- 23538228
TI  - Safety in numbers: hyperdiploidy and prognosis.

PMID- 23538229
TI  - Ikaros, Notch, and GATA1 cross paths during megakaryopoiesis.

PMID- 23538230
TI  - CARD9: at the intersection of mucosal and systemic antifungal immunity.

PMID- 23538231
TI  - Megakaryocytes put a foot through the door.

PMID- 23538232
TI  - Wnts heal by restraining angiogenesis.

PMID- 23538233
TI  - Design, synthesis and biological activities of Nilotinib derivates as antitumor
      agents.
AB  - A novel class of Nilotinib derivatives, B1-B20, were synthesized in high yields
      using various substituted anilines. All the title compounds were evaluated for
      their inhibitory activities against Bcr-Abl and antiproliferative effects on
      human leukemia cell (K562). The pharmacological results indicated that some
      compounds exhibited promising anticancer activity. In particular, compound B14
      containing tertiary amine side chain exhibited Bcr-Abl inhibitory activity
      similar to that of Nilotinib. It was suggested that the introduction of the
      tertiary amine moiety could improve Bcr-Abl inhibitory activity and antitumor
      effects.

PMID- 23538234
TI  - Novel hybrids of natural isochroman-4-one bearing N-substituted isopropanolamine
      as potential antihypertensive candidates.
AB  - A series of novel hybrids of natural isochroman-4-one bearing isopropanolamine
      moiety were designed, synthesized and evaluated for their antihypertensive
      activity. It was found that compound IIId, prepared by hybridizing N-isopropyl
      substituted isopropanolamine functionality to a phenolic oxygen of isochroman-4
      one, exhibited potent beta(1)-adrenoceptor blocking effect comparable to the well
      known antihypertensive drug propranolol. Additionally, IIId significantly reduced
      the systolic and diastolic blood pressure in SHRs by over 40%, which was
      obviously stronger than the lead compounds 7,8-dihydroxy-3-methyl-isochroman-4
      one (XJP) and its analogue XJP-B. Overall, IIId may be a promising
      antihypertensive candidate for further investigation.

PMID- 23538235
TI  - Reply: To PMID 23083673.

PMID- 23538236
TI  - Effect of probiotic supplementation during pregnancy and breast-feeding on the
      allergic sensitization in the infantile eczema.

PMID- 23538237
TI  - Orthotopic detaenial sigmoid neobladder after radical cystectomy: technical
      considerations, complications and functional outcomes.
AB  - PURPOSE: In recent years the orthotopic neobladder has gained increasing
      popularity in patients who undergo radical cystectomy. However, there are only a
      few reports of orthotopic neobladders reconstructed from the sigmoid without
      detubularization. We investigated the complications and functional outcomes of
      the orthotopic sigmoid neobladder reconstructed using our detaenial technique.
      MATERIALS AND METHODS: We performed a retrospective study of the detaenial
      sigmoid neobladder in 210 consecutive patients who underwent radical cystectomy
      at our institution from January 2003 to March 2010. ANOVA was used to investigate
      urodynamic finding differentials with time. Univariable and multivariable
      analyses were done to determine factors influencing continence. RESULTS: Median
      followup was 48 months. Early complications (90 days or less) were observed in 65
      patients (31%). Late complications (greater than 90 days) were observed in 45
      patients (21.5%). Five-year daytime and nighttime complete continence rates were
      74.6% and 57.1%, respectively. Younger age was the only independent factor
      associated with complete continence during the day (OR 2.342, 95% CI 1.803-3.041,
      p <0.001) and night (OR 1.193, 95% CI 1.087-1.310, p <0.001). Mean maximal
      capacity and post-void residual urine were 328.8 and 22.2 ml, respectively. The
      mean maximal flow rate was 18.5 ml per second. The mean end filling pressure,
      pressure at maximal capacity and maximal intravesical pressure were 35.8, 55 and
      60.6 cm H2O, respectively. These parameters remained stable with time (each p
      >0.05). CONCLUSIONS: This study confirms that detaenial sigmoid neobladder is a
      safe, feasible alternative for urinary diversion.

PMID- 23538238
TI  - Effect of prior radiotherapy and ablative therapy on surgical outcomes for the
      treatment of rectourethral fistulas.
AB  - PURPOSE: We evaluate the impact of pelvic radiation and ablative therapy on the
      surgical repair of rectourethral fistula. MATERIALS AND METHODS: A total of 45
      patients with rectourethral fistulas were identified from a prospective database.
      From 1998 to 2010 a total of 49 surgical reconstructive procedures were
      performed. Fistula formation was secondary to radiation (brachytherapy, external
      beam radiation) and ablative therapy (cryotherapy or high intensity focused
      ultrasound) in 29 patients. The approach for surgical repair and clinical
      outcomes were analyzed to identify the impact of radiation and ablative therapy
      on successful fistula repair. RESULTS: Median patient age was 68 years and mean
      followup was 42 months (IQR 7, 71). A primary repair was more frequently
      attempted (15 of 16 [94%] vs 6 of 29 [21%], p <0.0001) and successful in
      nonradiation/ablation cases (13 of 15 [87%] vs 1 of 6 [17%], p = 0.003). Patients
      with prior radiation/ablation were significantly more likely to require permanent
      colostomy (25 of 29 [86%] vs 0%, p <0.0001) and permanent urinary diversion as
      part of fistula management (27 of 29 [93%] vs 1 of 16 [6%], p <0.0001). Of the 6
      patients with radiation/ablation induced fistula who underwent primary repair, 4
      subsequently required urinary diversion for fistula recurrence, 1 is symptomatic
      with recurrence and 1 (who presented with a 0.5 cm fistula) has had no evidence
      of fistula recurrence. CONCLUSIONS: Unlike the repair of a rectourethral fistula
      after surgical intervention, which is typically amenable to primary repair, most
      patients with severe radiation and ablation induced fistula will require urinary
      diversion with or without permanent colostomy. Thus, permanent urinary diversion
      should be considered early in the surgical management of these cases.

PMID- 23538239
TI  - Familiarity and self-reported compliance with American Urological Association
      best practice recommendations for use of thromboembolic prophylaxis among
      American Urological Association members.
AB  - PURPOSE: Thromboprophylaxis with subcutaneous heparin or low molecular weight
      heparin is now an integral part of national surgical quality and safety
      assessment efforts, and has been incorporated into the current AUA Best Practice
      Statement. We evaluated familiarity and compliance with the AUA Best Practice
      Statement, assessed practice patterns in terms of perioperative
      thromboprophylaxis and specifically examined self-reported compliance in high
      risk patients undergoing radical cystectomy. MATERIALS AND METHODS: An electronic
      survey was sent to AUA members with valid e-mail addresses (10,966). Associations
      between AUA Best Practice Statement adherence and factors such as urological
      specialty, graduation year and guideline familiarity were assessed using chi
      square analyses and generalized estimating equations. RESULTS: With 1,210 survey
      responses the largest group of respondents was urological oncologists and/or
      laparoscopic/robotic specialists (26.0%). This group was more likely to use
      thromboprophylaxis than nonurological oncologists and/or laparoscopic/robotic
      specialists in high risk patients (OR 1.3, CI 1.1-1.5). Respondents aware of the
      AUA Best Practice Statement guidelines (50.7%) were more likely to use
      thromboprophylaxis (OR 1.4, CI 1.2-1.6). Although 18.1% of urological oncologists
      and/or laparoscopic/robotic specialists and 34.2% of nonurological oncologists
      and/or laparoscopic/robotic specialists avoided routine thromboprophylaxis in
      patients undergoing radical cystectomy, the former were more likely to use
      thromboprophylaxis (p <0.0001) than other respondents. Urologists graduating
      after the year 2000 used thromboprophylaxis in high risk patients undergoing
      radical cystectomy more often than did earlier graduates (79.2% vs 63.4%, p
      <0.0001). CONCLUSIONS: Although younger age and self-reported urological
      oncologist and/or laparoscopic/robotic specialist status correlated strongly with
      thromboprophylaxis use, self-reported adherence to AUA Best Practice Statement
      was low, even in high risk cases with clear AUA Best Practice Statement
      recommendations such as radical cystectomy. These data identify opportunities for
      quality improvement in patients undergoing major urological surgery.

PMID- 23538240
TI  - Optimal frequency of shock wave lithotripsy in urolithiasis treatment: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - PURPOSE: The optimal frequency of shock wave lithotripsy in urolithiasis has not
      been well determined. MATERIALS AND METHODS: A search of MEDLINE, Web of Science
      and the Cochrane Library was performed. All randomized controlled trials
      including articles and meeting abstracts that compared the effects of different
      frequencies (120, 90 and 60 shock waves per minute) of shock wave lithotripsy
      were included in analysis. The review process followed the guidelines of the
      Cochrane Collaboration. RESULTS: Nine randomized controlled trials including
      1,572 cases were identified. Overall success rates and success rates for large
      stones (greater than 10 mm) were significantly lower in the 120 vs 60 (p <0.001
      and p = 0.002, respectively) and in the 120 vs 90 (p <0.001 and p = 0.02,
      respectively) shock waves per minute groups, but similar between the 90 and 60
      shock waves per minute groups. Treatment duration was significantly shorter in
      the 120 vs 60, 120 vs 90 and 90 vs 60 shock waves per minute groups (all p
      <0.001). Success rates for small stones (less than 10 mm), complication rates and
      total shock waves had no significant differences among the 3 groups. CONCLUSIONS:
      Decreasing the frequency from 120 to 60 shock waves per minute increased overall
      success rates. While the treatment duration of 60 shock waves per minute was much
      greater, 90 shock waves per minute seemed to be optimal, especially for large
      stones. A frequency of 120 shock waves per minute might still be recommended for
      small stones.

PMID- 23538241
TI  - Prospective study using a new bulking agent for the treatment of vesicoureteral
      reflux: polyacrylamide hydrogel.
AB  - PURPOSE: Vesicoureteral reflux is frequently diagnosed in the pediatric
      population. Endoscopic treatment has become a popular form of first-line therapy.
      Available products offer good short-term success rates. However, the cost of
      these injected implants is an issue. We evaluated the success of endoscopic
      treatment for vesicoureteral reflux using polyacrylamide hydrogel. MATERIALS AND
      METHODS: We performed a single center, single surgeon, prospective, off-label
      study using polyacrylamide hydrogel to treat vesicoureteral reflux. All patients
      underwent endoscopic subureteral double hydrodistention implantation technique
      injection followed by renal ultrasound and voiding cystourethrogram at 3 months
      postoperatively to confirm the absence of de novo hydronephrosis and correction
      of vesicoureteral reflux (grade 0). RESULTS: A total of 40 patients (69 refluxing
      ureters) underwent polyacrylamide hydrogel injection. Median age at surgery was
      50 months. Bilateral reflux was identified in 29 patients (73%). Nine patients
      had duplex systems, 2 with reflux into both moieties. Reflux was graded using the
      International Reflux Study in Children grading system, with grade I seen in 9
      ureters, II in 17, III in 20, IV in 18 and V in 5. Mean volume injected was 1.1
      ml. Success rate for grade I to III vesicoureteral reflux at 3 months after a
      single treatment was 87%, and the overall success for all grades was 81.2%.
      CONCLUSIONS: Off-label use of polyacrylamide hydrogel injection therapy for
      primarily low grade vesicoureteral reflux demonstrates that the technique and
      short-term success rates are comparable to the most popular bulking agent,
      dextranomer/hyaluronic acid. These results suggest that further trials comparing
      polyacrylamide hydrogel and dextranomer/hyaluronic acid would be worthwhile.

PMID- 23538242
TI  - Risk factors for delayed hematuria following photoselective vaporization of the
      prostate.
AB  - PURPOSE: Photoselective vaporization of the prostate has become an increasingly
      popular option for the treatment of benign prostatic hyperplasia. However,
      delayed bleeding has been raised as a potential issue as more cases are
      performed. We characterize delayed bleeding after photoselective vaporization of
      the prostate and identify associated risk factors. MATERIALS AND METHODS: We
      defined delayed gross hematuria as any complaint of hematuria following hospital
      discharge, and further stratified it as delayed gross hematuria requiring
      emergency department evaluation, hospital admission, continuous bladder
      irrigation, transfusions or reoperation. We performed an explicit chart review of
      290 patients who underwent photoselective vaporization of the prostate at a
      single center from 2002 through 2009. Exposures of interest included age,
      prostate volume, followup duration, operative factors (watts/joules), and use of
      oral anticoagulation therapy or 5alpha-reductase inhibitors. RESULTS: Delayed
      gross hematuria occurred in 33.8% of patients during an average followup of 33
      months. For 8.5% of patients the bleeding was severe enough to prompt
      presentation to the emergency department. For 4.8% of patients hospitalization
      was required and for 4.5% reoperation was required. Multivariate analysis
      revealed that the odds of bleeding increased with prostate size (OR 1.08, 1.03
      1.14), longer followup (OR 1.35, 1.12-1.62) and anticoagulant use (OR 3.35, 1.43
      7.83), and decreased with increasing age (OR 0.71, 0.51-0.98) and use of a 5alpha
      reductase inhibitor (OR 0.41, 0.24-0.73). CONCLUSIONS: Delayed hematuria occurs
      commonly after photoselective vaporization of the prostate but severe hematuria
      is rare. Larger prostate size, longer followup and use of anticoagulation were
      associated with a higher risk of delayed gross hematuria while preoperative
      5alpha-reductase inhibitor use and older age were protective.

PMID- 23538243
TI  - Uroflowmetry nomograms for healthy children 5 to 15 years old.
AB  - PURPOSE: We determined flow rates and generated flow rate-voided volume nomograms
      based on healthy children 5 to 15 years old voiding spontaneously in their
      natural environment. MATERIALS AND METHODS: A total of 824 healthy school
      children of both genders were enrolled. A single uroflow record from each child
      was evaluated. A total of 103 children with a voided volume of less than 50 ml
      and/or a staccato/interrupted uroflow pattern were excluded, and 721 records were
      analyzed. Data were evaluated using several mathematical formulas and goodness of
      fit was determined. Linear regression analysis was used to generate nomograms.
      RESULTS: Flow rates and voided volumes increased with increasing age, with the
      effect being more pronounced in girls. No significant difference was noted in
      uroflow rates from 5 to 10 years, but significant differences (p <0.001) started
      appearing at 11 to 15 years. Also no significant difference was noted in uroflow
      rates among children 11 to 15 years. Therefore, 2 age groups were designated,
      with group 1 consisting of patients 5 to 10 years old and group 2 consisting of
      patients 11 to 15 years old. There were 222 boys and 122 girls in group 1 and 240
      boys and 137 girls in group 2. In group 1 the maximum and average +/- SD flow
      rates were 15.26 +/- 4.54 ml per second and 7.68 +/- 3.26 ml per second,
      respectively, for boys and 17.98 +/- 6.06 ml per second and 9.19 +/- 4.23 ml per
      second, respectively, for girls. In group 2 these rates were 22.50 +/- 7.24 ml
      per second and 10.78 +/- 4.03 ml per second, respectively, for boys and 27.16 +/-
      9.37 ml per second and 13.48 +/- 5.21 ml per second, respectively, for girls.
      CONCLUSIONS: This large study, which expands the scant existing literature on
      uroflow parameters in healthy children, will hopefully promote wider application
      of uroflowmetry testing in the pediatric population.

PMID- 23538244
TI  - Quality cancer care.

PMID- 23538245
TI  - The Lymphedema Diagnosis and Treatment Cost Saving Act and steps must be double
      checked.

PMID- 23538246
TI  - Improving quality of life through pain control.
AB  - The pancreas is an externally excreting gland located in the abdominal cavity
      behind other organs. Difficulty palpating and viewing the pancreas often
      contributes to late diagnoses of tumors. In advanced disease, episodes of
      unmanaged pain have a negative impact on patients and family members and may
      affect many areas of well-being. Palliative care assists oncologists as well as
      patients and families with legitimate options for treating advanced disease,
      relieving symptom burdens and improving quality of life.

PMID- 23538247
TI  - Achieving quality oncology practice initiative certification through quality
      improvement.
AB  - The public and healthcare payers are increasingly looking to specialty
      designations and certifications to determine the quality of cancer centers. The
      Quality Oncology Practice Initiative (QOPI(r)) Certification Program is one way
      for cancer centers to demonstrate commitment to high-quality patient care.
      Achieving QOPI certification for the author's cancer center was driven by a nurse
      led quality improvement initiative. The result was an official designation that
      reflects the mission, vision, and philosophy of the organization.

PMID- 23538248
TI  - Ordering the correct genetic test: implications for oncology and primary care
      healthcare professionals.
AB  - Genetic testing for hereditary cancer syndromes is becoming increasingly more
      common. Once a mutation is detected in a family, other family members can undergo
      single-site mutation testing to determine if they have inherited the increased
      risk for developing cancer, with the intent of providing tailored and appropriate
      cancer prevention and early detection measures. Ordering the correct single-site
      test is critical to providing appropriate recommendations for cancer prevention
      and early detection.

PMID- 23538250
TI  - Oncology nurse communication barriers to patient-centered care.
AB  - Although quality communication has been identified as a necessary component to
      cancer care, communication skills training programs have yet to focus on the
      unique role of nurses. This study explored communication barriers as reported by
      seven nurse managers to better identify communication skills needed for oncology
      nurses to practice patient-centered care. Thematic analysis of transcripts was
      used to identify barriers to patient and family communication and desirable
      patient-centered nursing communication skills. Overall, the nurse managers
      reported that nurses experience patient and family communication difficulties as
      a result of inconsistent messages to patients and family from other healthcare
      staff. Physician assumptions about nursing left nurses feeling uncomfortable
      asking for clarification, creating a barrier to team communication processes.
      Patient-centered communication and care cannot be actualized for nurses unless
      team roles are clarified and nurses receive training in how to communicate with
      physicians, patients, and family. Therefore, the authors of this article created
      the COMFORT communication training protocol, and key concepts and resources for
      nurse communication training through COMFORT are detailed in this article.

PMID- 23538249
TI  - Chemotherapy-induced peripheral neuropathy: an algorithm to guide nursing
      management.
AB  - Oncology nurses play a critical role in the assessment and management of
      chemotherapy-induced peripheral neuropathy (CIPN). Baseline and ongoing
      evaluation of physical function is a critical but often overlooked aspect of
      assessment of CIPN. The diversity of symptoms and the complexity associated with
      neuromuscular assessment lead to challenges in evaluation and management of CIPN.
      To meet this challenge, the authors devised a feasible algorithm to guide
      oncology nurses in the assessment and management of CIPN using techniques that
      can easily be implemented in a variety of clinical settings. Managing pain,
      maintaining safety, and maximizing physical function are the primary goals for
      nursing management of CIPN.

PMID- 23538251
TI  - Palliative care communication in oncology nursing.
AB  - Oncology nurses consistently exhibit distress when communicating about end-of
      life topics with patients and families. Poor communication experiences and
      processes correlate with emotional distress, moral distress, and work-related
      stress. The National Consensus Project (NCP) for Quality Palliative Care
      developed clinical practice guidelines to establish quality standards for the
      practice of palliative care. NCP's guidelines are expressly intended as an
      interdisciplinary document and are representative of the inherent
      interdisciplinary nature of palliative care. Communication's value to palliative
      and oncology nursing is unique because those two specialties include a high
      frequency of challenging interactions for patients, families, and healthcare
      professionals. The COMFORT communication curriculum, a holistic model for
      narrative clinical communication in practice developed for use in early
      palliative care, is posed as a resource for oncology nurses with a series of
      practice case examples presented against the backdrop of NCP's eight domains of
      quality palliative care.

PMID- 23538252
TI  - A support group for fathers whose partners died from cancer.
AB  - Men who are raising dependent children after their spouses or partners have died
      from cancer face unique challenges adjusting to single parenthood while managing
      their grief and the grief of their children. Unfortunately, the needs of those
      widowers have been overlooked in the clinical literature and no published
      interventions are designed specifically for that population. The current article
      details the creation and implementation of a peer support group for fathers
      recently widowed because of their wives' deaths from cancer. Initial observations
      and emergent themes from the group are described. Group members suggested that
      they benefited from participation in the support group and that this form of
      psychosocial support is a promising intervention for fathers in similar
      circumstances.

PMID- 23538253
TI  - Tamoxifen benefits and CYP2D6 testing in women with hormone receptor-positive
      breast cancer.
AB  - Cancer intervention strategies have been increasingly focused on developing
      therapies that are personalized and tailored to each individual's unique genetic
      profile. Evolving understanding of the metabolism and pharmacogenomics of
      tamoxifen, an early example of targeted therapy for women with hormone receptor
      positive breast cancer, has created decision-making challenges for healthcare
      providers and their patients. This article reviews the pharmacology of tamoxifen,
      the genetics and physiology of the CYP2D6 enzyme system that has important
      effects on tamoxifen metabolism, and subset data analyses from large controlled,
      clinical trials that cast new light on previously held beliefs about the utility
      of CYP2D6 genotyping for predicting tamoxifen effectiveness and improved breast
      cancer outcomes in women with early-stage, hormone receptor-positive breast
      cancer.

PMID- 23538254
TI  - African American health disparities in lung cancer.
AB  - Lung cancer is a leading cause of cancer-related deaths in the United States and
      globally. African Americans experience significant differences in lung cancer
      incidence and mortality. Smoking is the single greatest risk for lung cancer,
      making smoking cessation programs a potentially fruitful approach for reducing
      the risk of lung cancer. Despite clinical practice guidelines that prompt nurses
      to advise patients to quit smoking, only a small percentage of nurses do so.
      Minority patients are less likely than Whites to receive smoking cessation
      advice. This article discusses recent findings on the pathophysiology and risks
      for lung cancer. The literature on smoking cessation research is examined to
      determine the features of successful cessation interventions. Recommendations are
      offered for enhancing tobacco cessation efforts in nursing practice, education,
      and research.

PMID- 23538255
TI  - The psychosocial impact of cancer-related infertility on women: a review and
      comparison.
AB  - The objective of the current article was to assess the psychosocial impact of
      treatment-related infertility or the possibility of infertility on young women
      with cancer in contrast to the general population. Literature on the subject of
      female infertility among the general population and treatment-related female
      infertility among young women with cancer was identified and examined in the
      context of what is known about the psychosocial impact of infertility among the
      general population. Women whose fertility was affected by cancer treatment were
      likely to experience negative emotional reactions, which can strain their
      relationships. Additional concerns included receiving inadequate information
      about infertility, enduring distress, and feeling uncertainty regarding fertility
      status.

PMID- 23538256
TI  - Impact of tobacco-control legislation.
AB  - Oncology nurses should be aware of smoking-related public health legislation and
      tobacco use prevention resources as well as increase their knowledge of psycho
      education materials, medications, and products available to aid smoking
      cessation. Smoking is the leading cause of preventable death; one out of five
      deaths in the United States is attributed to smoking. Each day, almost 4,000
      Americans younger than age 18 try their first cigarette, and 1,000 of those
      youths will become regular smokers. In 2009, House Resolution 1256: The Family
      Smoking Prevention and Tobacco Control Act gave the U.S. Food and Drug
      Administration the authority to regulate tobacco products with emphasis placed on
      prevention of the use by youth through graphic health warnings. Most states and
      many countries have enacted bans on smoking in all enclosed public places;
      however, some still allow smoking in adult-specific venues, such as bars, and
      some have not enacted any general statewide ban on smoking in any nongovernment
      owned spaces. Oncology nurses can be instrumental in advocating for tobacco
      control legislation as well as providing and supporting services focused on
      smoking cessation and the prevention of tobacco use.

PMID- 23538257
TI  - HIV- and AIDS-associated cancers.
AB  - One of the most significant world epidemics in history, HIV/AIDS, has been a
      research priority since its discovery in 1981. This review article provides an
      update on HIV/AIDS, with a specific focus on the diagnosis and care of patients
      with HIV- and AIDS-associated cancers.

PMID- 23538258
TI  - Discovering multiple myeloma early in ambulatory patients with chest pain.
AB  - Multiple myeloma (MM) is a systemic malignancy of plasma cells often
      characterized by sternal, rib, or back pain. This article describes how a patient
      who had chest pain for more than one month was mistakenly diagnosed with reflux
      esophagitis. Healthcare providers should be mindful of MM when determining the
      source of unidentified chest pain in patients.

PMID- 23538259
TI  - Implementing a dedicated education unit: a practice partnership with oncology
      nurses.
AB  - An urgent need exists to identify innovative and evidence-based educational
      methods to help oncology nurses provide safe and high-quality patient care. One
      promising solution is the dedicated education unit (DEU) educational model, which
      partners nursing faculty and skilled nursing clinicians to facilitate the
      clinical experience of undergraduate baccalaureate nursing students. This article
      describes the collaborative DEU initiative developed between a university school
      of nursing and a tertiary cancer center to provide senior nursing students with
      an innovative method to develop their competencies in oncology nursing practice
      and care.

PMID- 23538260
TI  - Histamine type 2 receptor antagonists as adjuvant treatment for resected
      colorectal cancer.

PMID- 23538261
TI  - Understanding the difficulty.

PMID- 23538262
TI  - Chemobrain in underserved African American breast cancer survivors: a qualitative
      study.
AB  - Although research has been conducted to address specific medical and psychosocial
      needs of breast cancer survivors, little has been done to address needs along the
      entire trajectory of care. One such need is chemobrain, a phenomenon recognized
      as an identifiable psychosocial cognitive change in breast cancer survivors. The
      purpose of this article is to present the findings of a qualitative study
      conducted with two focus groups of underserved African American breast cancer
      survivors. Four themes emerged from the transcribed interviews: the concept of
      chemobrain, variability among individuals, the stigma of chemobrain, and methods
      of coping. In addition, findings revealed that health professionals were not used
      by the participants as a resource to address the issues of chemobrain, which
      holds significant implications for practice. That fact highlights the
      implications for oncology nursing with respect to providing education and support
      for patients experiencing chemobrain. Nursing professionals are in a position to
      be a frontline resource for breast cancer survivors, providing information,
      education, and coping methods to help improve their quality of life.

PMID- 23538263
TI  - Carfilzomib: a next-generation proteasome inhibitor for multiple myeloma
      treatment.
AB  - Although the incidence of multiple myeloma (MM) is increasing, the median overall
      survival and the number of agents in the pipeline for treating MM also are
      increasing. Response rates higher than 80% are not uncommon in the frontline
      setting when the novel agents thalidomide, lenalidomide, and bortezomib are used
      in combination. Response rates and survival also have improved in disease that
      has relapsed after treatment with conventional therapies. The focus of research
      has now shifted to improving survival and disease response in patients refractory
      to current treatment paradigms. New agents are targeting new pathways, as well as
      existing mechanisms known to be effective, but with different safety profiles.
      Carfilzomib is a potent, selective, irreversible inhibitor of the ubiquitin
      proteasome pathway. The drug is a next-generation proteasome inhibitor found to
      be safe and effective for patients with relapsed and refractory MM, where
      treatment options are limited. As with any newly approved agent, one should
      recognize that drugs within the same class will be administered differently and
      often cause dissimilar treatment-related toxicities. Oncology nurses are crucial
      to the successful administration of chemotherapeutic agents such as carfilzomib,
      and an understanding of management techniques is paramount to quality patient
      care.

PMID- 23538264
TI  - Chronic morphine exposure and its abstinence alters dendritic spine morphology
      and upregulates Shank1.
AB  - Exposure to chronic drugs of abuse has been reported to produce significant
      changes in postsynaptic protein profile, dendritic spine morphology and synaptic
      transmission. In the present study we demonstrate alterations in dendritic spine
      morphology in the frontal cortex and nucleus accumbens of mice following chronic
      morphine treatment as well as during abstinence for two months. Such alterations
      were accompanied with significant upregulation of the postsynaptic protein Shank1
      in synaptosomal enriched fractions. mRNA levels of Shank1 was also markedly
      increased during morphine treatment and during withdrawal. Studies of the
      different postsynaptic proteins at the protein and mRNA levels showed significant
      alterations in the morphine treated groups compared to that of saline treated
      controls. Taken together, these observations suggest that Shank1 may have an
      important role in the regulation of spine morphology induced by chronic morphine
      leading to addiction.

PMID- 23538265
TI  - Spatio-temporal spread of neuronal death after focal photolysis of caged
      glutamate in neuron/astrocyte co-cultures.
AB  - Glutamate-mediated excitotoxicity is now accepted as a major mechanism of
      ischemic neuronal damage. In the infarct core region, massive neuronal death is
      observed, but neurons in the surroundings of the core (ischemic penumbra) seem
      viable at the time of stroke. Several hours or days after a stroke, however, many
      neurons in the penumbra will undergo delayed neuronal death (DND). The mechanisms
      responsible for such DND are not fully understood. In this study, we investigated
      whether and how glutamate-mediated localized excitotoxic neuronal death affects
      surrounding neurons and astrocytes. To induce spatially-restricted excitotoxic
      neuronal death, a caged glutamate was focally photolyzed by a UV flash in
      neuron/astrocyte co-cultures. Uncaging of the glutamate resulted in acute
      neuronal death in the flashed area. After that, DND was observed in the
      surroundings of the flashed area late after the uncaging. In contrast, DND was
      not observed in neuron-enriched cultures, suggesting that functional changes in
      astrocytes, not neurons, after focal acute neuronal death were involved in the
      induction of DND. The present in vitro study showed that the spatially-restricted
      excitotoxic neuronal death resulted in DND in the surroundings of the flashed
      area, and suggested that the nitric oxide (NO)-induced reduction in the
      expression of astrocytic GLT-1 was responsible for the occurrence of the DND.

PMID- 23538266
TI  - Presynaptic kainate receptor-mediated bidirectional modulatory actions:
      mechanisms.
AB  - Kainate receptors (KARs) are members of the glutamate receptor family, which also
      includes two other ionotropic subtypes, i.e. NMDA- and AMPA-type receptors, and
      types I, II and III metabotropic glutamate receptors. KARs mediate synaptic
      transmission postynaptically through their ionotropic capacity, while
      presynaptically, they modulate the release of both GABA and glutamate through
      operationally diverse modus operandi. At hippocampal mossy fiber (MF)-CA3
      synapses, KARs have a biphasic effect on glutamate release, such that, depending
      on the extent of their activation, a facilitation or depression of glutamate
      release can be observed. This modulation is posited to contribute to important
      roles of KARs in short- and long-term plasticity. Elucidation of the modes of
      action of KARs in their depression and facilitation of glutamate release is
      beginning to gather impetus. Here we will focus on the cellular mechanisms
      involved in the modulation of glutamate release by presynaptic KAR activation at
      MF-CA3 synapses, a field that has seen significant progress in recent years.

PMID- 23538267
TI  - Vildagliptin more effectively achieves a composite endpoint of HbA1c < 7.0%
      without hypoglycaemia and weight gain compared with glimepiride after 2 years of
      treatment.
AB  - This post hoc analysis reports that overall proportion of patients achieving a
      composite endpoint of HbA1c<7.0% (<53.0 mmol/mol) without hypoglycaemia and
      weight gain was higher with vildagliptin than glimepiride after 2 years in type 2
      diabetes patients inadequately controlled on metformin monotherapy, regardless of
      age and duration of diabetes.

PMID- 23538268
TI  - Gestational diabetes in a multiethnic population of Spain: clinical
      characteristics and perinatal outcomes.
AB  - AIMS: To compare clinical characteristics and perinatal outcomes between
      immigrant and Spanish women with gestational diabetes mellitus (GDM) in a
      multiethnic population of Barcelona and to identify factors independently
      associated with the development of large-for-gestational-age (LGA) infants.
      METHODS: Prospective study of women with GDM from five ethnic groups (Caucasian,
      South-Central Asian, Latin American, East Asian and Moroccan) at a single
      institution in Barcelona between 2004 and 2011. Maternal, gestational and newborn
      characteristics were recorded. RESULTS: The cohort included 456 patients. In
      univariate analyses, Moroccan women had more frequently a pre-gestational body
      mass index (BMI)>25 kg/m(2) (76.4%, P=0.012), while East Asian women had lower
      BMI (23.41 +/- 2.79 kg/m(2), P<0.001), less need for insulin therapy (14.3%,
      P=0.013) and the highest rate of spontaneous labor (69.8%, P=0.014) and eutocic
      delivery (63.8%, P=0.032). Also, Latin American women had a higher rate of
      Cesarean section (52.9%, P<0.001) and LGA infants (28.6%, P=0.004), and their
      newborns had lower umbilical cord pH (7.23 +/- 0.06, P=0.005) and Apgar scores (9
      [4-10], P<0.01) and a higher incidence of neonatal hypoglycemia (51.4%, P=0.045).
      Logistic regression analysis identified pre-gestational BMI (OR: 1.18; 95% CI:
      1.09-1.27), pregnancy weight gain (OR: 1.19; 95% CI: 1.1-1.28) and insulin use
      during gestation (OR: 2.29; 95% CI: 1.09-4.82) as predictors of LGA infants.
      CONCLUSIONS: Significant ethnic differences were found in clinical
      characteristics and perinatal outcomes of women with GDM. Latin American women
      had a higher frequency of adverse perinatal outcomes. Pregestational BMI,
      pregnancy weight gain and insulin use during pregnancy were independent
      predictors of LGA.

PMID- 23538269
TI  - The value of repeat neuroimaging for epilepsy at a tertiary referral centre: 16
      years of experience.
AB  - PURPOSE: Magnetic resonance imaging (MRI) is the investigation of choice for
      detecting structural lesions that underlie and may accompany epilepsy. Despite
      advances in imaging technology, 20-30% of patients with refractory focal epilepsy
      have normal MRI scans. We evaluated the role of repeated imaging with improved
      MRI technology - an increase in field strength from 1.5T to 3T and superior head
      coils - in detecting pathology not previously seen. METHODS: Retrospective review
      of a large cohort of patients attending a tertiary epilepsy referral centre who
      underwent MRI at 1.5T (1995-2004) and subsequently 3T (2004-2011) with improved
      head coils. Scan reports were reviewed for the diagnoses and medical notes for
      the epilepsy classification. RESULTS: 804 patients underwent imaging on both
      scanners, the majority with focal epilepsy (87%). On repeat scanning at 3T, 37%
      of scans were normal and 20% showed incidental findings. Positive findings
      included hippocampal sclerosis (13%), malformations of cortical development (8%),
      other abnormalities (4%) and previous surgery (18%). A total of 37 (5%) relevant
      new diagnoses were made on the 3T scans not previously seen at 1.5T. The most
      common new findings were hippocampal sclerosis, focal cortical dysplasia and
      dysembryoplastic neuroepithelial tumour. These findings affected patient
      management with several patients undergoing neurosurgery. CONCLUSIONS: The higher
      field strength and improved head coils were associated with a clinically relevant
      increased diagnostic yield from MRI. This highlights the importance of
      technological advances and suggests that rescanning patients with focal epilepsy
      and previously negative scans is clinically beneficial.

PMID- 23538270
TI  - Newly-diagnosed pediatric epilepsy is associated with elevated autoantibodies to
      glutamic acid decarboxylase but not cardiolipin.
AB  - Glutamic acid decarboxylase autoantibodies (GADA) and anti-cardiolipin
      autoantibodies (ACA) have been detected in adult subjects with epilepsy, though
      the functional implications of these findings are a matter of debate. This study
      aimed to determine the prevalence of GADA and ACA and to investigate their
      clinical significance in pediatric subjects with newly-diagnosed epilepsy. For
      this purpose GADA and ACA were assessed by enzyme-linked immunosorbent assays in
      208 pediatric patients with newly-diagnosed epilepsy and 128 controls. The
      clinical data (results of electroencephalography, magnetic resonance imaging, 6
      month outcome etc.) was compared to antibody test results. Our study revealed
      GADA in 14 (6.7%) patients with epilepsy and in 1 (0.8%) control, which was a
      statistically significant difference (P=0.010; Chi-square test). The GADA
      positive and -negative patients had similar clinical characteristics. The
      prevalence of ACA in patients with epilepsy (6.3%) was not significantly
      different than controls (2.6%). These results suggest that GADA is associated
      with epilepsy in a subgroup of newly-diagnosed pediatric patients. Further
      studies are required to determine the prognostic significance and pathogenic role
      of GADA among pediatric subjects with epilepsy.

PMID- 23538271
TI  - Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation.
AB  - Cardiac arrhythmias are associated with abnormal channel function due to
      mutations in ion channel genes. Epilepsy is a disorder of neuronal function also
      involving abnormal channel function. It is increasingly demonstrated that the
      etiologies of long QT syndrome and epilepsy may partly overlap. However, only a
      few genetic studies have addressed a possible link between cardiac and neural
      channelopathies. We describe a family showing the association between Brugada
      syndrome and epilepsy in which a known mutation in the SCN5A gene (p.W1095X,
      c.3284G>A) was identified. We suggest that this mutation can be responsible for
      cardiac and brain involvement, probably at different developmental age in the
      same individual. This observation confirms the possibility that SCN5A mutations
      may confer susceptibility for recurrent seizure activity, supporting the emerging
      concept of a genetically determined cardiocerebral channelopathy.

PMID- 23538272
TI  - OutFOXing myeloid cells in atherosclerosis with FoxOs.

PMID- 23538273
TI  - The many faces of Orai.

PMID- 23538274
TI  - To activate or not to activate: the existential dilemma of an enhancer.

PMID- 23538275
TI  - Role of the ubiquitin proteasome system in the heart.
AB  - Proper protein turnover is required for cardiac homeostasis and, accordingly,
      impaired proteasomal function appears to contribute to heart disease. Specific
      proteasomal degradation mechanisms underlying cardiovascular biology and disease
      have been identified, and such cellular pathways have been proposed to be targets
      of clinical relevance. This review summarizes the latest literature regarding the
      specific E3 ligases involved in heart biology, and the general ways that the
      proteasome regulates protein quality control in heart disease. The potential for
      therapeutic intervention in Ubiquitin Proteasome System function in heart disease
      is discussed.

PMID- 23538278
TI  - Hypercalcemia: from a rainy city to a sunny desert.

PMID- 23538279
TI  - Metabolic consequences of craniopharyingioma and their management.
AB  - Most patients diagnosed with craniopharyngioma survive long-term, but suffer many
      consequences of the disease and its treatment. Among the metabolic consequences,
      there is a high prevalence of panhypopituitarism and diabetes insipidus, mainly
      due to the surgical treatment. Obesity is also more prevalent in these patients
      than in the general population, and gets worse with time. It is a consequence of
      a diminished basal metabolic rate and a lower physical activity compared to that
      of matched controls, with a similar or lower caloric intake. Many different
      hormonal alterations that could be responsible for those changes in the energy
      balance have been found. Patients whose tumor involved the hypothalamus are more
      prone to develop obesity and its consequences. Cardiovascular risk factors are
      also more prevalent in these patients, leading to a high cardiovascular morbidity
      and mortality. Sleep disturbances, dysfunction in thermoregulation and thirst and
      a lower bone mineral density can also be found. Although randomized clinical
      trials comparing different treatments are lacking, it looks like therapeutic
      strategies have a minor influence on the risk of long-term sequelae. 

PMID- 23538277
TI  - MicroRNA in cardiovascular calcification: focus on targets and extracellular
      vesicle delivery mechanisms.
AB  - Cardiovascular calcification is a prominent feature of chronic inflammatory
      disorders-such as chronic kidney disease, type 2 diabetes mellitus, and
      atherosclerosis-that associate with significant morbidity and mortality. The
      concept that similar pathways control both bone remodeling and vascular
      calcification is widely accepted, but the precise mechanisms of calcification
      remain largely unknown. The central role of microRNAs (miRNA) as fine-tune
      regulators in the cardiovascular system and bone biology has gained acceptance
      and has raised the possibility for novel therapeutic targets. Additionally,
      circulating miRNAs have been proposed as biomarkers for a wide range of
      cardiovascular diseases, but knowledge of miRNA biology in cardiovascular
      calcification is very limited. This review focuses on the role of miRNAs in
      cardiovascular disease, with emphasis on osteogenic processes. Herein, we discuss
      the current understanding of miRNAs in cardiovascular calcification. Furthermore,
      we identify a set of miRNAs common to diseases associated with cardiovascular
      calcification (chronic kidney disease, type 2 diabetes mellitus, and
      atherosclerosis), and we hypothesize that these miRNAs may provide a molecular
      signature for calcification. Finally, we discuss this novel hypothesis with
      emphasis on known biological and pathological osteogenic processes (eg,
      osteogenic differentiation, release of calcifying matrix vesicles). The aim of
      this review is to provide an organized discussion of the known links between
      miRNA and calcification that provide emerging concepts for future studies on
      miRNA biology in cardiovascular calcification, which will be critical for
      developing new therapeutic strategies.

PMID- 23538276
TI  - KATP channels and cardiovascular disease: suddenly a syndrome.
AB  - ATP-sensitive potassium (KATP) channels were first discovered in the heart 30
      years ago. Reconstitution of KATP channel activity by coexpression of members of
      the pore-forming inward rectifier gene family (Kir6.1, KCNJ8, and Kir6.2 KCNJ11)
      with sulfonylurea receptors (SUR1, ABCC8, and SUR2, ABCC9) of the ABCC protein
      subfamily has led to the elucidation of many details of channel gating and pore
      properties. In addition, the essential roles of Kir6.x and SURx subunits in
      generating cardiac and vascular KATP(2) and the detrimental consequences of
      genetic deletions or mutations in mice have been recognized. However, despite
      this extensive body of knowledge, there has been a paucity of defined roles of
      KATP subunits in human cardiovascular diseases, although there are reports of
      association of a single Kir6.1 variant with the J-wave syndrome in the ECG, and 2
      isolated studies have reported association of loss of function mutations in SUR2
      with atrial fibrillation and heart failure. Two new studies convincingly
      demonstrate that mutations in the SUR2 gene are associated with Cantu syndrome, a
      complex multi-organ disorder characterized by hypertrichosis, craniofacial
      dysmorphology, osteochondrodysplasia, patent ductus arteriosus, cardiomegaly,
      pericardial effusion, and lymphoedema. This realization of previously
      unconsidered consequences provides significant insight into the roles of the KATP
      channel in the cardiovascular system and suggests novel therapeutic
      possibilities.

PMID- 23538280
TI  - Reference values of waist circumference and waist/hip ratio in children and
      adolescents of Merida, Venezuela: comparison with international references.
AB  - OBJECTIVE: To collect regional reference values of waist circumference (WC), and
      waist/hip ratio (WHR) in children and adolescents from Merida, Venezuela, and to
      compare them to international references. SUBJECTS AND METHODS: A total of 919
      students aged 9-17 years from public and private educational establishments were
      assessed. Weight, height, WC, and WHR were measured. Outliers (+/- 3 SD Z-Score)
      were excluded from the data collected. Percentile distribution of the tested
      variables was done by age and sex. RESULTS: Fifty-one percent of subjects were
      female, and 52.7% were from public institutions. WC (p=0.001) and WHR (p=0.0001)
      were statistically higher in boys. With advancing age, WC increased in both
      sexes, while WHR showed the opposite behavior (p=0.0001 for both). The 90th
      percentile (pc) for WC ranged from 69.7 and 83.6 cm in girls and from 69.2 and
      86.7 cm in boys. The 90th pc values of WHR ranged from 0.79 and 0.91 in girls and
      from 0.86 and 0.93 in boys. Overall, our WC and WHR values were lower than North
      American values and similar to those of some Latin American references.
      CONCLUSION: Percentile reference charts for WC and WHR specific for age and sex,
      obtained from a representative sample of children and adolescents from Merida,
      Venezuela, are provided. They may be used regionally, both for individual
      assessment and to implement prevention policies.

PMID- 23538281
TI  - Targeting thyroid diseases with TSH receptor analogs.
AB  - The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of
      thyroid function and growth, and is the key antigen in several pathological
      conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various
      effective treatment strategies are currently available for many of these clinical
      conditions such as antithyroid drugs or radioiodine therapy, but they are not
      devoid of side effects. In addition, treatment of complications of Graves'
      disease such as Graves' ophthalmopathy is often difficult and unsatisfactory
      using current methods. Recent advances in basic research on both in vitro and in
      vivo models have suggested that TSH analogs could be used for diagnosis and
      treatment of some of the thyroid diseases. The advent of high-throughput
      screening methods has resulted in a group of TSH analogs called small molecules,
      which have the potential to be developed as promising drugs. Small molecules are
      low molecular weight compounds with agonist, antagonist and, in some cases,
      inverse agonist activity on TSHR. This short review will focus on current
      advances in development of TSH analogs and their potential clinical applications.
      Rapid advances in this field may lead to the conduct of clinical trials of small
      molecules related to TSHR for the management of Graves' disease, thyroid cancer,
      and thyroid-related osteoporosis in the coming years. 

PMID- 23538282
TI  - Multilevel obstruction in the left heart during pregnancy.

PMID- 23538283
TI  - Extensive xanthomas and severe subclinical atherosclerosis in homozygous familial
      hypercholesterolemia.

PMID- 23538284
TI  - We are sorry to announce that Henry Spilberg, who was the journal executive
      publisher with Elsevier, has moved to another publisher. Introduction.

PMID- 23538285
TI  - Differences in the antigen structures of Corynebacterium pseudotuberculosis and
      the induced humoral immune response in sheep and goats.
AB  - Caseous lymphadenitis (CLA), a disease affecting sheep and goats, is caused by
      Corynebacterium pseudotuberculosis (Cp). Eradication programs are based on the
      serological identification of Cp infected animals. However, available diagnostic
      ELISAs are not similarly suitable for sheep and goats. In the present study the
      comparison of antigens revealed major species specific differences between sheep
      and goat derived Cp field isolates as well as between field isolates and the Cp
      ATCC reference strains. Furthermore, we found species-specific differences in the
      anti-Cp humoral immune response between sheep and goats. The analysis of band
      frequency was able to distinguish between immunodominant and non-immunodominant
      protein bands. The 150 kDa, 74 kDa, 48 kDa, and 30 kDa antigens were
      immunodominant in both, sheep and goats. Interestingly, the most commonly used
      diagnostic antigen, i.e. the 30 kDa phospholipase D (PLD), was recognized by 100%
      of the Cp positive goats but only by 70% of the Cp positive sheep. Furthermore,
      analysis of field sera revealed that there were a particular percentage of Cp
      positive sera which reacted negative with the PLD. In conclusion our results
      clearly showed that (1) the application of a combination of further defined
      immunodominant Cp antigens - in addition to the PLD antigen - and (2)
      consideration of species-specific differences in the anti-Cp immune response will
      substantially contribute to the improvement of Cp serological diagnostics and to
      effective eradication programs in both sheep and goats.

PMID- 23538286
TI  - Gene-environment interaction on cognition: a twin study of childhood maltreatment
      and COMT variability.
AB  - The functional variant Val(158)Met in the coding sequence of COMT gene is
      involved in the modulation of dopamine availability in the prefrontal cortex in
      both clinical and general population samples. It has been suggested that the
      interplay between this genotype and early environmental factors could be used to
      predict the observed variation in cognitive flexibility. However, other genetic
      variants and environmental factors may confound the association and produce the
      inconsistent results commonly found in the literature. In the present study we
      aimed at testing putative interaction mechanisms between childhood maltreatment
      and COMT genotypic variability that might explain a proportion of the observed
      variability of cognitive flexibility in the population. Our design was based on a
      sample of adult monozygotic twins, which allowed us to test these effects free
      from potential genetic and shared-environmental confounding factors. Results
      showed that unique environmental effects of childhood maltreatment significantly
      impacted cognitive performance among Met/Met subjects. Interestingly, the
      direction of the association indicated that exposure to early stressful
      experiences was associated with enhanced cognitive flexibility in this genotype
      group. These results suggest that COMT may operate as a plasticity gene that
      provides differential cognitive capacity to respond to environmental stressors.

PMID- 23538287
TI  - The putative influence of the agr operon upon survival mechanisms used by
      Clostridium acetobutylicum.
AB  - The bacterium Clostridium acetobutylicum produces acids as an energy-yielding
      process during exponential growth. An acidic environment, however, is toxic to
      the cells and two survival mechanisms are in place to prevent them from dying.
      Firstly, during a solventogenesis phase, the cells take up these acids and
      convert them to solvents, thus raising the environmental pH. Secondly, the cells
      undergo sporulation to form highly resistant spores capable of surviving extreme
      conditions. One possible regulatory mechanism for these processes is the
      accessory gene regulatory (agr) quorum-sensing system, which is thought to
      coordinate cell population density with cell phenotype. We model this system to
      monitor its putative effect upon solventogenesis and the sporulation-initiation
      network responsible for triggering spore formation. We demonstrate that a high
      population density should be able to induce both solventogenesis and sporulation,
      with variations to the parameter set allowing sporulation alone to be triggered;
      additional distinct signals are capable of restoring the solventogenic response.
      We compare the agr system of C. acetobutylicum with that of Staphylococcus aureus
      in order to investigate why the differences in feedback between the two systems
      may have evolved. Our findings indicate that, depending upon the mechanism of
      interaction between the agr system and the sporulation-initiation network, the
      clostridial agr circuitry may be in place either to moderate the number of spores
      that are formed (in order for this number to reflect the urgency of the
      situation), or simply as an energy-saving strategy.

PMID- 23538289
TI  - Schizophrenia and other psychotic disorders in DSM-5.
AB  - Whereas improving validity and reliability of psychiatric diagnoses were key
      objectives in the development of DSM-5, enhancing clinical utility was the
      primary goal. With reference to psychotic disorders, changes addressed
      limitations in DSM-IV while incorporating new information about the nature of
      these disorders generated over the past twenty years. With regard to
      schizophrenia, variation in distinct psychopathological dimensions has been found
      to better account for the heterogeneity of schizophrenia than traditional
      subtypes. Resulting changes in DSM-5 will likely include elimination of the
      classic subtypes of schizophrenia and addition of unique psychopathological
      dimensions, along with elimination of the special treatment of Schneiderian
      "first-rank symptoms." In view of the poor reliability and limited validity of
      DSM-IV schizoaffective disorder, a clearer definition is provided in DSM-5.
      Considering the discrepant treatment of catatonia in DSM-IV, it is treated
      consistently across the DSM-5 manual. Minor changes are made in the definition of
      delusional disorder to reduce spurious comorbidity and unnecessary complexity. A
      new category of "attenuated psychosis syndrome" is included in the appendix as a
      condition for further study. In this article, major likely revisions in the DSM-5
      (due to be published in May 2013) criteria for schizophrenia spectrum and other
      psychotic disorders are summarized and their implications for clinical practice
      are discussed.

PMID- 23538290
TI  - Safety and efficacy review of inhaled loxapine for treatment of agitation.
AB  - Agitation is common in patients with acute schizophrenia and bipolar disorder,
      and rapid and effective treatment of acute agitation is an important clinical
      goal. Loxapine is a first-generation antipsychotic medication available in the
      United States in oral form for more than three decades. In December 2012, an
      inhaled version of vaporized loxapine was approved by the U.S. FDA for the
      treatment of agitated adults in the context of schizophrenia or bipolar disorder.
      In this review, we examine available literature to describe efficacy and safety
      of inhaled loxapine in healthy patients and in those with pulmonary compromise.
      Limitations of the current evidence base to predict efficacy in "real world"
      patients are described, and safeguards necessary for appropriate use in
      psychiatric acute care settings are discussed.

PMID- 23538291
TI  - Differential diagnosis of psychosis in a deaf inpatient with language dysfluency:
      a case study.
AB  - This case report demonstrates challenges diagnosing psychosis in language
      dysfluent deaf patients. Treatment of a 34-year-old deaf man on an inpatient
      psychiatric unit is described. He had a history of physical aggression and
      possible symptoms of paranoia and thought disorganization, in addition to
      learning difficulties and minimal language skills. The patient was placed on a
      combined hearing/deaf inpatient unit, received specialized programming for deaf
      patients and was prescribed risperidone and divalproex sodium to treat his
      aggressive behavior and possible psychosis. Uncertainty if the patient were
      having psychotic symptoms remained throughout his hospitalization, although he
      improved behaviorally and was discharged after 13 months of treatment. The
      patient's pre-existing language deficits made accurate diagnosis and appropriate
      treatment challenging. It is important for clinicians to be aware of the
      frequency of language dysfluency in the deaf inpatient population and have a
      strategy for evaluating and treating this complex subgroup of deaf people.

PMID- 23538292
TI  - Increased CD38 expression in T cells and circulating anti-CD38 IgG autoantibodies
      differentially correlate with distinct cytokine profiles and disease activity in
      systemic lupus erythematosus patients.
AB  - CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity
      responsible for both the synthesis and the degradation of several Ca(2+)
      mobilizing second messengers. In mammals, CD38 also functions as a receptor. In
      this study CD38 expression in CD4(+), CD8(+), or CD25(+) T cells was
      significantly higher in systemic lupus erythematosus (SLE) patients than in
      Normal controls. Increased CD38 expression in SLE T cells correlated with plasma
      levels of Th2 (IL-4, IL-10, IL-13) and Th1 (IL-1beta, IL-12, IFN-gamma, TNF
      alpha) cytokines, and was more prevalent in clinically active SLE patients than
      in Normal controls. In contrast, elevated anti-CD38 IgG autoantibodies were more
      frequent in clinically quiescent SLE patients (SLEDAI=0) than in Normal controls,
      and correlated with moderate increased plasma levels of IL-10 and IFN-gamma.
      However, clinically active SLE patients were mainly discriminated from quiescent
      SLE patients by increased levels of IL-10 and anti-dsDNA antibodies, with odds
      ratios (ORs) of 3.7 and 4.8, respectively. Increased frequency of anti-CD38
      autoantibodies showed an inverse relationship with clinical activity (OR=0.43),
      and in particular with the frequency of anti-dsDNA autoantibodies (OR=0.21).
      Increased cell death occurred in CD38(+) Jurkat T cells treated with anti-CD38(+)
      SLE plasmas, and not in these cells treated with anti-CD38(-) SLE plasmas, or
      Normal plasmas. This effect did not occur in CD38-negative Jurkat T cells,
      suggesting that it could be attributed to anti-CD38 autoantibodies. These results
      support the hypothesis that anti-CD38 IgG autoantibodies or their associated
      plasma factors may dampen immune activation by affecting the viability of CD38(+)
      effector T cells and may provide protection from certain clinical SLE features.

PMID- 23538293
TI  - Effects of different uphill interval-training programs on running economy and
      performance.
AB  - PURPOSE: Runners use uphill running as a movement-specific form of resistance
      training to enhance performance. However, the optimal parameters for prescribing
      intervals are unknown. The authors adopted a dose-response design to investigate
      the effects of various uphill interval-training programs on physiological and
      performance measures. METHODS: Twenty well-trained runners performed an
      incremental treadmill test to determine aerobic and biomechanical measures, a
      series of jumps on a force plate to determine neuromuscular measures, and a 5-km
      time trial. Runners were then randomly assigned to 1 of 5 uphill interval
      training programs. After 6 wk all tests were repeated. To identify the optimal
      training program for each measure, each runner's percentage change was modeled as
      a quadratic function of the rank order of the intensity of training. Uncertainty
      in the optimal training and in the corresponding effect on the given measure was
      estimated as 90% confidence limits using bootstrapping. RESULTS: There was no
      clear optimum for time-trial performance, and the mean improvement over all
      intensities was 2.0% (confidence limits +/-0.6%). The highest intensity was
      clearly optimal for running economy (improvement of 2.4% +/- 1.4%) and for all
      neuromuscular measures, whereas other aerobic measures were optimal near the
      middle intensity. There were no consistent optima for biomechanical measures.
      CONCLUSIONS: These findings support anecdotal reports for incorporating uphill
      interval training in the training programs of distance runners to improve
      physiological parameters relevant to running performance. Until more data are
      obtained, runners can assume that any form of high-intensity uphill interval
      training will benefit 5-km time-trial performance.

PMID- 23538294
TI  - Hierarchically porous metastable beta-Ag2WO4 hollow nanospheres: controlled
      synthesis and high photocatalytic activity.
AB  - Metastable materials have received extensive attention due to their unique
      physical and chemical properties which are different from those of the
      thermodynamically stable phase. However, the variety of reported metastable
      materials is still very limited owing to difficulties in the effective synthesis
      of pure metastable materials because they can easily transform into the
      corresponding stable phases. Therefore, it is crucial and a great challenge to
      explore new metastable materials with novel and fascinating functions. In this
      study, hierarchically porous metastable beta-Ag2WO4 hollow nanospheres with a
      diameter of 50-500 nm were prepared for the first time by a facile precipitation
      reaction between AgNO3 and Na2WO4 in the presence of poly(methacrylic acid)
      (PMAA). It was found that the PMAA not only provided a spherical soft template to
      induce the formation of hollow nanospheres but also worked as an inhibitor to
      prevent the phase transformation from thermodynamically unstable beta-Ag2WO4 to
      stable alpha-Ag2WO4 phase. The resultant metastable beta-Ag2WO4 hollow
      nanospheres show a larger specific surface area (165.5 m(2) g(-1)) owing to the
      hierarchically porous structure (micropores, mesopores, and macropores),
      resulting in a high photocatalytic performance for the decomposition of methyl
      orange and phenol aqueous solutions. The present work can provide some new
      insight into the smart design and preparation of other new metastable hollow
      materials, and the prepared metastable beta-Ag2WO4 hollow nanospheres have
      various potential applications in chemical reactors, drug-delivery carriers,
      solar cells, catalysis, and separation and purification fields.

PMID- 23538295
TI  - An improved method for collecting breath from 3- to 7-year-old children.
AB  - Breath sampling and analysis provide healthcare professionals with a practical,
      noninvasive diagnostic measurement for children with a variety of
      gastrointestinal (GI) disorders. New biomarkers found in human breath have been
      investigated and provide the opportunity to diagnose bacterial overgrowth and
      other underlying causes of GI dysfunction. Although several protocols have been
      described previously regarding breath sampling, few have demonstrated the
      feasibility of collection in young children. This communication introduces a
      simple game that allows for 3- to 7-year-old children to practice breath
      exhalation to give a proper breath sample in a relaxed and comfortable
      environment. The technique described offers clinicians a creative approach for
      obtaining breath samples from a child by reducing the apprehension and anxiety
      associated with the research and clinical environment. 

PMID- 23538296
TI  - Nonalcoholic fatty liver disease: for better or worse, blame the gut microbiota?
AB  - Nonalcoholic fatty liver disease (NAFLD) is a major clinical consequence for
      people with obesity and metabolic syndrome and is also associated with enteral
      and parenteral nutrition. Early studies suggested that altered gut microbiota
      might contribute to obesity by affecting energy harvest from the diet and energy
      storage in the host. Recent evidence in humans as well as in animal models has
      linked gut microbiota to the development of NAFLD through the gut-liver axis.
      With bacterial overgrowth and increased intestinal permeability observed in
      patients with NAFLD and in animal models, gut-derived bacterial products such as
      endotoxin (lipopolysaccharide) and bacterial DNA are being delivered to the liver
      through the portal vein and then activate Toll-like receptors (TLRs), mainly TLR4
      and TLR9, and their downstream cytokines and chemokines, leading to the
      development and progression of NAFLD. Given the limited data in humans, the role
      of gut microbiota in the pathogenesis of NAFLD is still open to discussion.
      Prebiotics and probiotics have been attempted to modify the microbiota as
      preventive or therapeutic strategies on this pathological condition. Their
      beneficial effects on NALFD have been demonstrated in animal models and limited
      human studies. However, prospective, appropriately powered, randomized,
      controlled clinical trials are needed to determine whether prebiotics and
      probiotics and other integrated strategies to modify intestinal microbiota are
      efficacious therapeutic modalities to treat NALFD. 

PMID- 23538297
TI  - Crossing the wall: the opening of endothelial cell junctions during infectious
      diseases.
AB  - Vascular endothelial cells (ECs) form a barrier that plays a crucial role in the
      health and integrity of tissues by regulating the passage of molecules, liquids
      and immune cells. Dysfunctions or disruption of this barrier leads to edema,
      inflammation, and associated pathologies. During infection, ECs control
      transmigration of cells by a complex system of molecules. However pathogens can
      hijack this pathway to invade ECs and/or tissues. They can also trigger the
      opening of intercellular junction, apoptosis of ECs or activation of the immune
      system, which in turn lead to the destruction of the endothelial wall and
      subsequent edema. Activation of immune cells by pathogens can also enhance the
      destruction of EC and edema. The review summarizes the state-of-the-art knowledge
      on the key steps of the complex interactions between the endothelial wall,
      pathogens, and the immune system that lead to the opening of junctions and/or
      destruction of the wall, enhancing pathology. A better understanding of these
      points will allow the development of adjunctive treatments to be used in
      combination with therapies targeting pathogens, with the aim of protecting the
      wall and improving the recovery of patients with severe infectious diseases.

PMID- 23538298
TI  - The equilibrium between long and very long chain ceramides is important for the
      fate of the cell and can be influenced by co-expression of CerS.
AB  - Ceramides are synthesized by six different ceramide synthases (CerS1-6), which
      differ in their specificity to produce ceramides of distinct chain length. We
      investigated the impact of CerS-co-transfection on ceramide production and
      apoptosis and proliferation in HCT-116 cells. Over-expression of CerS4 and CerS6
      enhanced the level of C(16:0)-Cer twofold, that of C(18:0)- and C(20:0)-Cer up to
      sevenfold, in comparison to vector control transfected cells, whereas over
      expression of CerS2 had no effect on the level of very long chain ceramide
      C(24:0)- and C(24:1)-Cer. Instead over-expression of CerS2 together with CerS4 or
      CerS6 increased the activity of CerS2 against very-long-chain ceramides about
      twofold. In contrast, co-expression of CerS4 with CerS6 inhibited slightly the
      production of C20:0-ceramide in comparison to cells over-expressing CerS4 alone,
      whereas the activity of CerS6 seemed not to be affected by other CerS.
      Interestingly, down-regulation of ELOVL1 had a comprehensive effect on the
      synthesis of very long chain ceramides which possibly point to a requirement for
      ELOVL1 expression for full CerS2-activity. Co-expression of CerS2 with
      CerS4/CerS6 reversed the inhibitory effect of long chain ceramides on cell
      proliferation and the induction of apoptosis. Even though we observed a twofold
      increase in total ceramide levels after co-expression of CerS2 with CerS4/CerS6,
      we detected no effect on cell proliferation. These data indicate that an increase
      in ceramide production per se is not critical for cell survival, but the
      equilibrium between long and very long chain ceramides and possibly
      protein/protein interactions determine the fate of the cell.

PMID- 23538299
TI  - Glucose plays a main role in human fibroblasts adaptation to hypoxia.
AB  - Hypoxia induces severe changes in cell biology, particularly affecting energy
      production pathways. Although the theme has been widely investigated,
      particularly in transformed cells, studies of the mitochondrial bioenergetics of
      normal cells exposed to both prolonged hypoxic periods and low or null glucose
      concentration have been scarcely addressed. To evaluate the mitochondrial changes
      of cells exposed to the latter conditions, we set experiments in which the
      contribution of the mitochondrial energy production was maximized at the expenses
      of low glycolysis. Human fibroblasts were exposed to 1% oxygen tension, a hypoxic
      condition experimentally established for these cells, and grown in glucose
      deficient media. At variance with fibroblasts grown in 5-25 mM glucose,
      fibroblasts grown in glucose deficiency adapted to hypoxia by reducing only
      slightly the mitochondrial mass and preserving a well structured network as it
      occurs in normoxia. Moreover, the oxidative phosphorylation (OXPHOS) rate of the
      mitochondria was enhanced, due to increased OXPHOS complexes level. The master
      transcriptional modulator induced by hypoxia HIF-1alpha and BNIP3, a factor
      activating mitochondrial autophagy, were expressed both in the presence and in
      the absence of glucose, but to a lower level in the latter condition. Similarly,
      the microtubule-associated protein light chain 3 active fragment (LC3-II), a
      typical marker of autophagy, was found less expressed in glucose-free medium than
      in the presence of glucose. Therefore, our data show for the first time that
      glucose availability significantly affects the hypoxia-induced HIF-1/BNIP3
      response, and in particular glucose absence results in enhancing the OXPHOS rate.

PMID- 23538300
TI  - Comparison of bumetanide- and metolazone-based diuretic regimens to furosemide in
      acute heart failure.
AB  - INTRODUCTION: Limited data exist comparing the efficacy and safety of bumetanide-
      or metolazone-based diuretic regimens to furosemide in acute heart failure (HF).
      Our purpose was to evaluate the comparative effect on urine output (UO) and renal
      function between these regimens. METHODS: A retrospective study of hospitalized
      HF patients treated with continuous infusion furosemide (CIF), combination
      furosemide plus metolazone (F + M), or continuous infusion bumetanide (CIB).
      Primary end points were between regimen comparisons for change in mean hourly UO
      versus baseline and incidence of worsening renal function. RESULTS: Data on 242
      patients with acute HF (age 58 +/- 12 years, 63% male, left ventricular ejection
      fraction 38% +/- 17%) were analyzed (160 CIF, 42 F + M, 40 CIB). The mean
      duration of diuretic regimens was 41 +/- 32 hours. Compared to baseline, all
      regimens increased mean hourly UO (P < .0001 for all), with greater increases
      with F + M (109 +/- 171 mL) and CIB (90 +/- 90 mL) compared to CIF (48 +/- 103
      mL; P = .009). Incidence of worsening renal function was not different between
      regimens; however, blood urea nitrogen (BUN) tended to increase more with F + M
      (4.4 +/- 9.8 mg/dL) and CIB (4.3 +/- 9.7 mg/dL) than CIF (1.8 +/- 10.8 mg/dL), P
      = .09. The incidence of hyponatremia was higher with F + M and CIB. Differences
      in UO, BUN, and hyponatremia were retained in the subgroup analysis limited to
      patients with baseline serum creatinine <1.5 mg/dL, where renal function between
      the groups was not different. CONCLUSION: Compared to CIF, F + M or CIB was
      associated with greater increases in UO. No difference in the incidence of
      worsening renal function was found; however, electrolyte abnormalities may be
      more prevalent when furosemide is combined with metolazone or when bumetanide is
      used. These therapeutic differences warrant prospective study.

PMID- 23538301
TI  - Cardioprotective effect of calcitriol on myocardial injury induced by
      isoproterenol in rats.
AB  - BACKGROUND: Calcitriol (CAL), an active form of vitamin D, plays a vital role in
      controlling cardiac hypertrophy and heart failure. The aim of the present study
      is to explore the effects of CAL and to elucidate its underlying mechanisms on
      myocardial injury induced by isoproterenol (ISO). METHODS: Myocardial impairment
      was induced by the subcutaneous injection of ISO in adult male Sprague-Dawley
      rats, and the therapeutic effect of CAL was assessed. Biometric and
      echocardiographic parameters, interstitial fibrosis, oxidant-antioxidant status,
      and protein expression relevant to the mitochondrial apoptosis pathway were then
      measured. RESULTS: Calcitriol treatment improved the cardiac injury resulting
      from excessive ISO stimulation, as supported by the suppression of the
      development of myocardial hypertrophy, interstitial fibrosis, and H2O2 level in
      heart tissue. The decreased superoxide dismutase and catalase activities induced
      by ISO were also improved by CAL. Finally, the administration of CAL
      downregulated the protein expression of Bax and caspase-9. CONCLUSIONS: This
      study provides evidence that CAL ameliorated cardiac hypertrophy, interstitial
      fibrosis, and oxidative stress in ISO-induced cardiac injury and might play a
      vital cardioprotective role in such injuries.

PMID- 23538303
TI  - Neural mechanisms underlying heterogeneity in the presentation of anxious
      temperament.
AB  - Children with an anxious temperament (AT) are at risk for developing psychiatric
      disorders along the internalizing spectrum, including anxiety and depression.
      Like these disorders, AT is a multidimensional phenotype and children with
      extreme anxiety show varying mixtures of physiological, behavioral, and other
      symptoms. Using a well-validated juvenile monkey model of AT, we addressed the
      degree to which this phenotypic heterogeneity reflects fundamental differences or
      similarities in the underlying neurobiology. The rhesus macaque is optimal for
      studying AT because children and young monkeys express the anxious phenotype in
      similar ways and have similar neurobiology. Fluorodeoxyglucose (FDG)-positron
      emission tomography (FDG-PET) in 238 freely behaving monkeys identified brain
      regions where metabolism predicted variation in three dimensions of the AT
      phenotype: hypothalamic-pituitary-adrenal (HPA) activity, freezing behavior, and
      expressive vocalizations. We distinguished brain regions that predicted all three
      dimensions of the phenotype from those that selectively predicted a single
      dimension. Elevated activity in the central nucleus of the amygdala and the
      anterior hippocampus was consistently found across individuals with different
      presentations of AT. In contrast, elevated activity in the lateral anterior
      hippocampus was selective to individuals with high levels of HPA activity, and
      decreased activity in the motor cortex (M1) was selective to those with high
      levels of freezing behavior. Furthermore, activity in these phenotype-selective
      regions mediated relations between amygdala metabolism and different expressions
      of anxiety. These findings provide a framework for understanding the mechanisms
      that lead to heterogeneity in the clinical presentation of internalizing
      disorders and set the stage for developing improved interventions.

PMID- 23538304
TI  - Rapid electron exchange between surface-exposed bacterial cytochromes and Fe(III)
      minerals.
AB  - The mineral-respiring bacterium Shewanella oneidensis uses a protein complex,
      MtrCAB, composed of two decaheme cytochromes, MtrC and MtrA, brought together
      inside a transmembrane porin, MtrB, to transport electrons across the outer
      membrane to a variety of mineral-based electron acceptors. A proteoliposome
      system containing a pool of internalized electron carriers was used to
      investigate how the topology of the MtrCAB complex relates to its ability to
      transport electrons across a lipid bilayer to externally located Fe(III) oxides.
      With MtrA facing the interior and MtrC exposed on the outer surface of the
      phospholipid bilayer, the established in vivo orientation, electron transfer from
      the interior electron carrier pool through MtrCAB to solid-phase Fe(III) oxides
      was demonstrated. The rates were 10(3) times higher than those reported for
      reduction of goethite, hematite, and lepidocrocite by S. oneidensis, and the
      order of the reaction rates was consistent with those observed in S. oneidensis
      cultures. In contrast, established rates for single turnover reactions between
      purified MtrC and Fe(III) oxides were 10(3) times lower. By providing a
      continuous flow of electrons, the proteoliposome experiments demonstrate that
      conduction through MtrCAB directly to Fe(III) oxides is sufficient to support in
      vivo, anaerobic, solid-phase iron respiration.

PMID- 23538305
TI  - Profile of John Gurdon and Shinya Yamanaka, 2012 Nobel laureates in medicine or
      physiology.

PMID- 23538306
TI  - Acute kidney injury: global health alert.

PMID- 23538307
TI  - Prevention of recurrent urinary tract infections.
AB  - Urinary tract infections (UTI) are among the most frequent bacterial infections
      in the community and health care setting. Mostly young and, to some extent,
      postmenopausal women are affected by recurrent UTI (rUTI) defined as >=3 UTI/year
      or >=2 UTI/half year. In contrast, rUTI is rare in healthy men. On the other
      hand, rUTI are frequently found in female and male patients with complicating
      urological factors, e.g. urinary catheters, infection stones. Remediable
      predisposing factors in uncomplicated rUTI in women are rare. In complicated rUTI
      the success depends mainly on the possibility to eliminate or at leastimprove the
      complicating risk factors. Continuous antibiotic prophylaxis or postcoital
      prophylaxis, if there is close correlation with sexual intercourse, are most
      effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and
      fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and
      quinolones should be restricted to specific indications. Antibiotic prophylaxis
      reduces the number of uropathogens in the gut and/or vaginal flora and reduces
      bacterial "fitness". Given the correct indication, the recurrence rate of rUTI
      can be reduced by about 90%. Due to possible adverse events and the concern of
      selecting resistant pathogens, according to the guidelines of the European
      Association of Urology antimicrobial prophylaxis should be considered only after
      counselling, behavioural modification and non-antimicrobial measures have been
      attempted. In postmenopausal patients vaginal substitution of oestriol should be
      started first. Oral or parenteral immunoprophylaxis is another option in patients
      with rUTI. Other possibilities with varying scientific evidence are prophylaxis
      with cranberry products, specific plant combinations or probiotics. The
      prophylaxis of catheter-associated UTI should employ strategies which result in a
      reduction of frequency and duration of catheter drainage of the urinary tract.
      The currently available catheter materials have only little influence on reducing
      catheter-associated rUTI.

PMID- 23538308
TI  - Actual treatment of overactive bladder and urge urinary incontinence.
AB  - Overactive bladder (OAB) is defined by its hallmark symptom, urgency. It can be
      associated with urge urinary incontinence (UUI), and dramatically impact the
      patients' quality of life. Etiologies of OAB are numerous, and under this common
      wording, virtually all the population is covered (men as well as women, patients
      with or without neurogenic disease, and all age categories). OAB and UUI
      management have been historically based on non-interventional therapies,
      antimuscarinics, and surgery. In the last decade, innovations in the treatment of
      this highly prevalent condition have been multiple, and further insights came
      from various horizons (drug invention, innovative use of existing drugs, new
      medical devices, tissue engineering, gene and cell therapy). Notably, the use of
      BoNT and neuromodulation techniques have deeply modified the algorithm of
      specialized OAB management, delaying surgery indications and offering mini
      invasive alternatives to patient refractory to behavioral and medical treatment.
      Whilst some of these techniques are about to reach maturity, numerous questions
      remain unsolved about their indications, long term effects, rank in the
      armamentarium, cost-effectiveness, hypothetical combination or sequential use.
      The present review depicts the actual wide range of options available for OAB
      management in adults, focusing on the latest evolutions. When relevant, a
      distinction was made between genders and OAB subtypes (idiopathic vs neurogenic)
      regarding treatment outcomes.

PMID- 23538310
TI  - Renal support in acute kidney injury.
AB  - Acute kidney injury requiring renal replacement therapy (RRT) is associated with
      an unacceptably high mortality rate. Despite the identification of the modality,
      timing and intensity of dialysis, membrane biocompatibility, hollow fiber and
      catheter properties as potential modifying factors, there is little convincing
      evidence for the superiority of one over the other. However, the available data
      suggest that the early initiation of RRT may be beneficial. A focused review of
      clinical trials and meta-analysis of clinical trials of RRT is provided.

PMID- 23538309
TI  - Hypertension and chronic kidney disease: controversies in pathogenesis and
      treatment.
AB  - The relationship between hypertension and chronic kidney disease (CKD) has long
      been the subject of controversy. The pathogenetic mechanisms of nephropathy in
      non-diabetic individuals with hypertension, as well as optimal hypertension
      treatment targets in populations with nephropathy remain important clinical
      concerns. This manuscript reviews breakthroughs in molecular genetics that have
      clarified the complex relationship between hypertension and kidney disease,
      answering the question of which factor comes first. An overview of the potential
      roles that hyperuricemia plays in the pathogenesis of hypertension and CKD and
      current blood pressure treatment guidelines in populations with CKD are
      discussed. The ongoing National Institutes of Health-sponsored Systolic Blood
      Pressure Intervention Trial (SPRINT) is underway to help answer these important
      questions. Enrollment of 9250 hypertensive SPRINT participants will be completed
      in 2013; important results on ideal blood pressure control targets for reducing
      nephropathy progression, cardiovascular disease end-points, and preserving
      cognitive function are expected. As such, many of the controversial aspects of
      hypertension management will likely be clarified in the near future.

PMID- 23538311
TI  - Polycystic kidney disease: new horizons and therapeutic frontiers.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) represents the most
      prevalent inherited kidney disease, and an important contributor to renal and
      systemic morbidity. Almost 20 years after the discovery of the Pkd-1 and Pkd-2
      genes, the exact molecular mechanisms of polycystic kidney disease pathogenesis
      still remain elusive. In the absence of a specific therapy for polycystic kidney
      disease, patients are treated for chronic kidney disease symptoms, like
      hypertension, anemia, hyperparathyroidism and pain. Intensive research on ADPKD
      and a variety of related complex cystic kidney disease syndromes revealed a
      network of intracellular signaling pathways that depend on ciliary function and
      include calcium- and cAMP-dependent mechanisms. Furthermore, proliferative and
      tissue patterning responses to mTOR, STAT, CDK and wnt signaling play an
      important role in various aspects of cystogenesis and represent further targets
      for therapy. Only a limited amount of clinical evidence from randomized
      controlled trials is currently available to evaluate treatment options. This
      includes ongoing trials of the vasopressin receptor-2 antagonist tolvaptan, as
      well as a set of studies that fail to show a clear therapeutic benefit of
      everolimus or sirolimus in PKD progression. Future research will involve the
      evaluation of small molecule inhibitors of growth factor receptor-, CDK- and STAT
      pathways, as well as the characterization of novel biomarkers of disease
      progression and therapeutic response.

PMID- 23538312
TI  - Leukocyte activation markers and oxidative status in chronic kidney disease.
AB  - AIM: In chronic kidney disease (CKD) cardiovascular risk is increased. Oxidative
      stress is strictly involved in the pathophysiology of this enhanced risk as well
      as leukocytes' activation. To better elucidate these phaenomena we evaluated some
      parameters of leukocyte activation and oxidative state on fasting blood samples
      obtained from CKD patients on conservative or hemodialysis (HD) treatment,
      compared to those obtained from control subjects. METHODS: We enrolled 41
      patients (25 men and 16 women, mean age 64.7 +/- 11.1 years) with CKD and 42
      patients (21 men and 21 women, mean age 66.83 +/- 14.8 years) with CKD on
      hemodialysis (HD) treatment. Hemodialyzed patients were evaluated before and
      after a standard HD session. Leukocyte activation was evaluated by determining
      plasma elastase and myeloperoxidase level employing ELISA methods. Lipid
      peroxidation was evaluated as thiobarbituric acid-reactive substances (TBARS),
      total antioxidant status using spectrophotometry. RESULTS: Elastase was higher in
      CKD on conservative and on HD treatment and its value increased after the HD
      session. Myeloperoxidase did not show any variation in CKD on conservative and HD
      treatment while after HD its value was increased. Lipid peroxidation was
      increased in CKD on conservative and on HD therapy and its value after dialysis
      showed no significant variation. Total antioxidant status was increased in CKD on
      HD treatment and significantly decreased after the HD session; no variation
      between normal controls and CKD subjects on conservative therapy was observed.
      CONCLUSION: Several aspects derive from these data considering the role of
      oxidative stress in the cardiovascular events that accompany CKD.

PMID- 23538313
TI  - A prospective randomized trial comparing three different analgesic techniques for
      pain control during transrectal ultrasound guided prostate biopsy: a single
      center experience.
AB  - AIM: The aim of this paper was to optimize pain control during transrectal
      ultrasound (TRUS) guided prostate biopsy, the efficacy and safety of three
      different analgesic techniques were compared. METHODS: Two hundred and forty
      patients were prospectively randomized into 3 groups before TRUS guided prostate
      biopsy. Group A received combined periprostatic nerve block (PPNB) and perianal
      intrarectal lidocaine-prilocaine (PILP) cream; group B: PILP cream; group C:
      PPNB. Pain was evaluated using 10-point Visual Analog Scale (VAS). RESULTS: VAS
      during TRUS was lower in groups A and B vs. C (mean 1.3,1.4 vs. 5.1, P<0.001);
      VAS for PPNB was lower in group A and group B vs. C (mean 1.1,1.3 vs. 3.5,
      P<0.001). VAS for sampling wase lower in group A as compared to B and C (mean
      0.6, 3.5 and 1.4, P<0.001). VAS on stratified analysis was significantly lower in
      groupA vs. B and C in patients <60 years, prostate >50 cc and those with lower
      anorectal compliance (P<0.001). The overall complication rate was similar in all
      three groups. CONCLUSION: The combination of PILP and PPNB provides better
      analgesia, especially in patients <60 years, prostate volume >50 cc and lower
      anorectal compliance as compared to two modalities used alone during the sampling
      part of TRUS guided prostate biopsy with no increase in the complication rate.

PMID- 23538314
TI  - Acute hepatitis C in patients undergoing hemodialysis: experience with high-dose
      interferon therapy.

PMID- 23538315
TI  - Effect of local blood flow in thermal regulation in diabetic patient.
AB  - The presence of dysautonomia in diabetic neuropathy is correlated with impairment
      of vasomotor activity that drives blood microcirculation. Microcirculation, in
      turn, plays an important role in thermoregulation. In this work, we investigate
      the changes between two different physiological conditions of diabetic patients,
      induced by FREMS application, in the control of skin temperature, using a
      minimally invasive experiment. Skin is warmed up to a fixed temperature (44 
      degrees C) for a few minutes, then the heat source is turned off, letting the
      skin recover its physiological temperature. Both temperature and local blood
      flow, the latter measured with laser Doppler, are monitored during the
      experiment. A simple model of the cooling phase is used to evaluate the time
      constants involved in the process. Results indicate that significant differences
      exist in the model parameters between the two conditions.

PMID- 23538316
TI  - Rosuvastatin in experimental brain trauma: improved capillary patency but no
      effect on edema or cerebral blood flow.
AB  - BACKGROUND: Microvascular dysfunction, characterized by edema formation secondary
      to increased blood-brain barrier (BBB) permeability and decreased blood flow,
      contributes to poor outcome following brain trauma. Recent studies have indicated
      that statins may counteract edema formation following brain trauma but little is
      known about other circulatory effects of statins in this setting. The objective
      of this study was to investigate whether statin treatment improves brain
      microcirculation early after traumatic brain injury, and whether microvascular
      effects are associated with altered production of nitric oxide and prostacyclin.
      METHODS: After fluid percussion injury, rats were randomized to intravenous
      treatment with 20mg/kg of rosuvastatin or vehicle. Brain edema (wet/dry weight),
      BBB integrity ((51)Cr-EDTA blood to brain transfer), cerebral blood flow ((14)C
      iodoantipyrine autoradiography), and number of perfused cortical capillaries
      (FITC-albumin fluorescence microscopy), were measured at 4 and 24h. NO and
      prostacyclin production was estimated from plasma concentration of the
      degradation products NO2- and NO3- (NOx) and 6-keto-PGF1-alpha, respectively.
      Sham injured animals were treated with vehicle and analyzed at 4h. RESULTS:
      Trauma resulted in brain edema, BBB dysfunction, and reduced cortical blood flow,
      with no effect of statin treatment. Trauma also induced a reduction in the number
      of perfused capillaries, which was improved by statin treatment. Statin treatment
      led to increased NOx levels and reduced mean arterial blood pressure. 6-Keto-PGF1
      alpha levels tended to increase after trauma, and were significantly reduced by
      rosuvastatin. CONCLUSIONS: Rosuvastatin treatment may improve microcirculation
      after traumatic brain injury by preserved patency of cerebral capillaries. This
      effect is associated with increased NO and reduced prostacyclin production. No
      effect on brain edema or BBB integrity was found.

PMID- 23538317
TI  - Southern Brazilian autumnal propolis shows anti-angiogenic activity: an in vitro
      and in vivo study.
AB  - The present study focuses on the effects of a hydro-alcoholic propolis extract
      collected in autumn (2010) in Santa Catarina State (Southern Brazil), on the
      angiogenesis, using in vitro and in vivo models. Cultures of human umbilical vein
      endothelial cells were used to assess the effects of propolis on viability,
      proliferation, and cell migration, as well as capillary tube formation. The
      propolis autumnal extracts significantly decreased the cell viability, based on
      CC50 values, which decreased (56%) from 297 to 130 MUg/ml in 24 h and 72 h of
      treatment, respectively (cytotoxicity assay). The process of cell proliferation
      was decreased by 81.7 to 48.4% due to exposure (72 h) to 130-180 MUg/ml of
      propolis extract, as compared with control (vehicle). In these same
      concentrations, the cell migration was also reduced by 39.6 to 12.6%,
      respectively (versus control). Furthermore, autumnal propolis extract (100-200
      MUg/ml) inhibited the tube-like structure formation (tubulogenesis) of
      endothelial cells on MatrigelTM (16.2-69.9% inhibition). The treatments performed
      in vivo with administration of 450 mg propolis.kg(-1) inhibited both angiogenesis
      and vasculogenesis by 82.3 and 66.5% in the chorioallantoic and yolk-sac
      membranes of chick embryos. Furthermore, by means of UV-vis-spectrophotometry,
      reverse phase-high performance liquid chromatography analysis and 1D and 2D
      nuclear magnetic resonance experiments reveal higher contents of flavonoids and
      total phenolic compounds with predominance of the flavonol quercetin and the
      phenolic acids, e.g., gallic acid, protocatechuic acid and chlorogenic acid in
      the propolis hydro-alcoholic extract. Our findings related to the anti
      proliferative, anti-migration, and anti-tubulogenic actions on human umbilical
      vein endothelial cell line agree with the inhibitory effects in the in vivo
      vessel formation exerted by propolis extract under study. The results also
      suggest that autumnal propolis extract might be potentially instrumental in
      providing alternative tools for angiogenic disease therapeutics.

PMID- 23538318
TI  - Clinical outcome of pediatric collagenous gastritis: case series and review of
      literature.
AB  - Collagenous gastritis (CG) is characterized by patchy subepithelial collagen
      bands. Effective treatment and the clinical and histological outcome of CG in
      children are poorly defined. The aim of this study is to summarize the published
      literature on the clinical outcome and response to therapy of pediatric CG
      including two new cases. We performed a search in Pubmed, OVID for related terms;
      articles including management and clinical and/or endo-histologic follow up
      information were included and abstracted. Reported findings were pooled in a
      dedicated database including the corresponding data extracted from chart review
      in our patients with CG. Twenty-four patients were included (17 females) with a
      mean age of 11.7 years. The clinical presentation included iron deficiency anemia
      and dyspepsia. The reported duration of follow up (in 18 patients) ranged between
      0.2-14 years. Despite most subjects presenting with anemia including one
      requiring blood transfusion, oral iron therapy was only documented in 12
      patients. Other treatment modalities were antisecretory measures in 13 patients;
      proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5),
      prednisolone (6), oral budesonide in 3 patients where one received it in fish oil
      and triple therapy (3). Three (13%) patients showed no clinical improvement
      despite therapy; conversely 19 out of 22 were reported with improved symptoms
      including 8 with complete symptom resolution. Spontaneous clinical resolution
      without antisecretory, anti-inflammatory or gastroprotective agents was noted in
      5 patients (4 received only supplemental iron). Follow up endo-histopathologic
      data (17 patients) included persistent collagen band and stable Mononuclear cell
      infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither
      collagen band thickness nor mononuclear cell infiltrate correlated with clinical
      course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1)
      raising the concern of long term malignant transformation. In summary, CG in
      children is a chronic disease, typically with a variable clinical response and an
      indolent course that is distinct from the adult phenotype. Long term therapy
      usually included iron supplementation but cannot be standardized, given the
      chronicity of the disease, variability of response and potential for adverse
      events.

PMID- 23538319
TI  - Exposure to 2,4-dichlorophenoxyacetic acid alters glucose metabolism in immature
      rat Sertoli cells.
AB  - The purpose of this study was to determine the effects of 2,4-D, an herbicide
      used worldwide also known as endocrine disruptor, in Sertoli cell (SC)
      metabolism. Immature rat SCs were maintained 50h under basal conditions or
      exposed to 2,4-D (100nM, 10MUM and 1mM). SCs exposed to 10MUM and 1mM of 2,4-D
      presented lower intracellular glucose and lactate content. Exposure to 10MUM of
      2,4-D induced a significant decrease in glucose transporter-3 mRNA levels and
      phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10MUM
      of 2,4-D. Exposure to 100nM and 10MUM also induced a decrease in lactate
      dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased
      in cells exposed to 1mM of 2,4-D. Exposure to 2,4-D altered glucose uptake and
      metabolization in SCs, as well as lactate metabolism and export that may result
      in impaired spermatogenesis.

PMID- 23538320
TI  - Tissue plasminogen activator induced delayed edema in experimental porcine
      intracranial hemorrhage: reduction with plasminogen activator inhibitor-1
      administration.
AB  - Hematoma puncture and subsequent clot lysis with recombinant tissue plasminogen
      activator (rtPA) emerged as an alternative therapy for spontaneous intracerebral
      hemorrhage (ICH) and is associated with delayed edema possibly counteracting the
      beneficial effects of hematoma volume reduction. We hypothesized that immediate
      reversal of rtPA activity after clot lysis and hematoma drainage diminishes edema
      formation. To test this hypothesis, we administered plasminogen activator
      inhibitor (PAI)-1 after rtPA lysis of experimentally induced ICH. A right frontal
      ICH was placed through a twist drill burr hole and autologous blood injection.
      Following creation of the frontal ICH, pigs received no further treatment (n =
      5), lysis with rtPA (n = 7), or lysis with rtPA followed by administration of PAI
      1 (n = 6). Hematoma and edema volumes were assessed with magnetic resonance
      imaging on days 0, 4, and 10. The rtPA significantly reduced hematoma volume and
      contributed to edema on day 10 after experimentally induced ICH. Administration
      of PAI-1 attenuated the rtPA-induced edema volume on day 10, but the hematoma
      volume reduction was less pronounced. In conclusion, PAI-1 attenuated delayed
      cerebral edema after rtPA lysis of experimental ICH but also reduced the lytic
      activity of rtPA. The combination of rtPA clot lysis with PAI-1 might have the
      potential to further improve the effect of the lytic therapy of ICH, but
      additional studies to define the optimum time point for PAI-1 administration are
      required. 

PMID- 23538321
TI  - Nuclear GAPDH: changing the fate of Muller cells in diabetes.
AB  - Muller cells, the primary glial cells are a crucial component of the retinal
      tissue performing a wide range of functions including maintaining the blood
      retinal barrier. Several studies suggest that diabetes leads to Muller cell
      dysfunction and loss. The pathophysiology of hyperglycemia-induced cellular
      injury of Muller cells remains only poorly understood. Recently, the concept that
      translocation of the predominantly cytosolic glycolytic enzyme glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) to the nucleus and its accumulation in this
      cellular compartment alters transcriptional events associated with cell death
      induction has gained major interest. High glucose conditions induce nuclear
      translocation and accumulation of GAPDH in the nucleus of Muller cells in vivo
      and in vitro. With regards to Muller cell dysfunction, the effects of nuclear
      accumulation of GAPDH are multifaceted. Considering the functional versatility of
      GAPDH including gene regulation, DNA repair, telomere protection, etc., it is of
      immense importance to explore possible GAPDH actions to unravel the mysteries
      around the role of GAPDH in hyperglycemia-induced cellular changes in order to
      develop novel therapeutic strategies. Therefore, this review focuses on the
      molecular events associated with the nuclear translocation of GAPDH and how it
      affects the fate of Muller cells in diabetes.

PMID- 23538322
TI  - Hematological and biochemical alterations in the fish Prochilodus lineatus caused
      by the herbicide clomazone.
AB  - The indiscriminate use of herbicides has led to the contamination of water
      bodies, possibly affecting the health of aquatic biota. Therefore, to evaluate
      the possible effects of the clomazone-based herbicide (Gamit((r)) 500) on the
      fish Prochilodus lineatus, juveniles were exposed for 96h to three concentrations
      (1, 5 and 10mgL(-1)) of clomazone, and an analysis was made of their
      hematological parameters: hemoglobin (Hb); hematocrit (Hct); red blood cell (RBC)
      count; mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean
      corpuscular hemoglobin concentration (MCHC) and biochemical parameters:
      glutathione S-transferase (GST); catalase (CAT); glutathione peroxidase (GPx) and
      acetylcholinesterase (AChE). Hct presented a significant decrease at the
      concentration of 10mgL(-1), while the parameters Hb, HCM and MCHC presented a
      significant decrease at the two higher concentrations, indicating an anemic
      condition. The RBC increased significantly at the lowest concentration, possibly
      due to the release of new red blood cells into the bloodstream in response to
      splenic contraction, which may occur as an adaptive response to the stressor
      agent. P. lineatus presented activation of the biotransformation pathway,
      indicated by augmented hepatic activity of the enzyme GST and hepatic activation
      of the antioxidant enzyme CAT at the higher concentrations. Liver GPx was
      significantly inhibited at the higher concentrations, which may indicate the
      efficient action of CAT in the elimination of H2O2 or its competition with GST
      for the same substrate (GSH). AChE activity in brain and muscle was inhibited at
      the higher concentrations, indicating the neurotoxic effects of the herbicide in
      the fish. The hematological and biochemical alterations led to the conclusion
      that the herbicide clomazone has toxic effects on the species P. lineatus, and
      that its presence in the environment may jeopardize the health of these animals.

PMID- 23538323
TI  - Protective effect of tannic acid on the brain of adult rats exposed to cadmium
      and lead.
AB  - Chronic exposure to Cd and Pb causes brain damage. Tannic acid (TA) is a very
      efficient chelator for metals. The effect of exposure to Cd and/or Pb and TA on
      the rats' brain were studied. Two experiments were carried. In experiment no. 1
      metals were administered with feed (7mg Cd and 50mgPb/kg) and TA with drink (0,
      0.5, 1, 1.5, 2 or 2.5% solutions). In experiment no. 2, rats received an aqueous
      solutions of [Cd (7 or 14mg/L) or Pb (50 or 100mg/L)] or 2% TA, alternatively
      every 7 days. In both experiments, TA had a positive effect only on reducing the
      accumulation of Cd. Exposure to metals resulted in an decrease of superoxide
      dismutase and catalase activity, whereas TA administration increased those. The
      results suggests that TA are more effective if taken parallel to food
      contaminated by Cd, and their effectiveness is higher if their intake is long
      term.

PMID- 23538324
TI  - A pilot study of seafood consumption and exposure to mercury, lead, cadmium and
      arsenic among infertile couples undergoing in vitro fertilization (IVF).
AB  - This cross-sectional pilot study was conducted to assess environmental exposures
      to toxic elements through seafood consumption, among infertile couples undergoing
      in vitro fertilization (IVF). Twenty-five women and 15 men completed a
      questionnaire, and provided biologic specimens for quantification of Hg, Pb, Cd,
      and As using ICP-MS. Consumption of 'mollusks' and 'shellfish' are associated
      with increased blood Hg. Other seafood consumption predicts blood Pb, and urine
      Cd and As. Though limited by small numbers and the cross-sectional design, these
      results suggest that consumption of specific seafood items increases exposure to
      toxic elements in couples undergoing IVF.

PMID- 23538325
TI  - Challenges in diagnosing mesenteric ischemia.
AB  - Early identification of acute mesenteric ischemia (AMI) is challenging. The wide
      variability in clinical presentation challenges providers to make an early
      accurate diagnosis. Despite major diagnostic and treatment advances over the past
      decades, mortality remains high. Arterial embolus and superior mesenteric artery
      thrombosis are common causes of AMI. Non-occlusive causes are less common, but
      vasculitis may be important, especially in younger people. Because of the unclear
      clinical presentation and non-specific laboratory findings, low clinical
      suspicion may lead to loss of valuable time. During this diagnostic delay,
      progression of ischemia to transmural bowel infarction with peritonitis and
      septicemia may further worsen patient outcomes. Several diagnostic modalities are
      used to assess possible AMI. Multi-detector row computed tomographic angiography
      is the current gold standard. Although computed tomographic angiography leads to
      an accurate diagnosis in many cases, early detection is a persistent problem.
      Because early diagnosis is vital to commence treatment, new diagnostic strategies
      are needed. A non-invasive simple biochemical test would be ideal to increase
      clinical suspicion of AMI and would improve patient selection for radiographic
      evaluation. Thus, AMI could be diagnosed earlier with follow-up computed
      tomographic angiography or high spatial magnetic resonance imaging. Experimental
      in vitro and in vivo studies show promise for alpha glutathione S transferase and
      intestinal fatty acid binding protein as markers for AMI. Future research must
      confirm the clinical utility of these biochemical markers in the diagnosis of
      mesenteric ischemia.

PMID- 23538326
TI  - Demography of Reintroduced Eastern Bluebirds and Brown-Headed Nuthatches.
AB  - Species reintroductions are used commonly as a tool for conservation, but
      rigorous, quantitative assessments of their outcome rarely occur. Such
      assessments are critical for determining success of the reintroduction and for
      identifying management actions needed to ensure persistence of reintroduced
      populations. We collected 9 years of demographic data on populations of brown
      headed nuthatches (Sitta pusilla) and Eastern bluebirds (Sialia sialis)
      reintroduced via translocation into Long Pine Key, Everglades National Park,
      Florida, USA. Realized population growth of brown-headed nuthatches was positive
      in the first 3 years after cessation of translocations (lambda2002 = 1.15, SE =
      0.13; lambda2003 = 1.28, SE = 0.12; lambda2005 = 1.32, SE = 0.20) but became
      negative thereafter (lambda2006 = 0.67, SE = 0.10; lambda2007 = 0.77, SE = 0.13).
      Realized growth rate for the Eastern bluebird population did not vary among years
      and indicated either a stable or a slowly declining population (lambda = 0.92, SE
      = 0.04). Reintroductions were a qualified success; they resulted in the re
      establishment of populations of both species, but neither population grew to the
      extent expected and both remained at risk of extinction.

PMID- 23538327
TI  - Evaluation of H3 histone methylation and colony formation in erythroid
      progenitors treated with thalidomide and sodium butyrate.
AB  - OBJECTIVES: beta-thalassemia and sickle cell disease are hemoglobinopathies with
      reduced/absent beta chains in the former and dysfunctional beta chains in the
      latter. In both conditions, up-regulation of hemoglobin F through demethylation
      can alleviate the symptoms. This can be attained with drugs such as thalidomide
      and sodium butyrate. MATERIALS AND METHODS: This study was performed on erythroid
      progenitors derived from CD133+ cord blood stem cells. Erythroid progenitors were
      treated with thalidomide and sodium butyrate in single and combined groups.
      Colony-formation potential in each group was evaluated by the colony assay. Real
      time polymerase chain reaction (RT-PCR) was used to evaluate the effect of these
      drugs on histone H3 lysine 27 (H3K27) methylation patterns. FINDINGS: Compared to
      other treatment groups, CD133+ cells treated with thalidomide alone produced more
      hematopoietic colonies. Thalidomide alone was also more effective in decreasing
      H3K27 methylation. CONCLUSIONS: Thalidomide shows superiority to sodium butyrate
      as a hypomethylating agent in this cell culture study, and it has the potential
      to become conventional treatment for sickle cell disease and beta-thalassemia.

PMID- 23538328
TI  - MDCT angiography to evaluate the therapeutic effect of PTVE for esophageal
      varices.
AB  - AIM: To evaluate the role of multi-detector row computed tomography (MDCT)
      angiography for assessing the therapeutic effects of percutaneous transhepatic
      variceal embolization (PTVE) for esophageal varices (EVs). METHODS: The subjects
      of this prospective study were 156 patients who underwent PTVE with cyanoacrylate
      for EVs. Patients were divided into three groups according to the filling range
      of cyanoacrylate in EVs and their feeding vessels: (1) group A, complete
      obliteration, with at least 3 cm of the lower EVs and peri-/EVs, as well as the
      adventitial plexus of the gastric cardia and fundus filled with cyanoacrylate;
      (2) group B, partial obliteration of varices surrounding the gastric cardia and
      fundus, with their feeding vessels being obliterated with cyanoacrylate, but
      without reaching lower EVs; and (3) group C, trunk obliteration, with the main
      branch of the left gastric vein being filled with cyanoacrylate, but without
      reaching varices surrounding the gastric cardia or fundus. We performed chart
      reviews and a prospective follow-up using MDCT images, angiography, and
      gastrointestinal endoscopy. RESULTS: The median follow-up period was 34 mo. The
      rate of eradication of varices for all patients was 56.4% (88/156) and the rate
      of relapse was 31.3% (41/131). The rates of variceal eradication at 1, 3, and 5
      years after PTVE were 90.2%, 84.1% and 81.7%, respectively, for the complete
      group; 61.2%, 49% and 42.9%, respectively, for the partial group; with no varices
      disappearing in the trunk group. The relapse-free rates at 1, 3 and 5 years after
      PTVE were 91.5%, 86.6% and 81.7%, respectively, for the complete group; 71.1%,
      55.6% and 51.1%, respectively, for the partial group; and all EVs recurred in the
      trunk group. Kaplan-Meier analysis showed P values of 0.000 and 0.000, and odds
      ratios of 3.824 and 3.603 for the rates of variceal eradication and relapse free
      rates, respectively. Cyanoacrylate in EVs disappeared with time, but those in the
      EVs and other feeding vessels remained permanently in the vessels without a
      decrease with time, which is important for the continued obliteration of the
      feeding vessels and prevention of EV relapse. CONCLUSION: MDCT provides excellent
      visualization of cyanoacrylate obliteration in EV and their feeding veins after
      PTVE. It confirms that PTVE is effective for treating EVs.

PMID- 23538329
TI  - Altruism in organ donation: an unnecessary requirement?
AB  - Altruism has long been taken to be the guiding principle of ethical organ
      donation in the UK, and has been used as justification for rejecting or allowing
      certain types of donation. We argue that, despite this prominent role, altruism
      has been poorly defined in policy and position documents, and used confusingly
      and inconsistently. Looking at how the term has been used over recent years
      allows us to define 'organ donation altruism', and comparing this with accounts
      in the philosophical literature highlights its theoretical shortcomings. The
      recent report from the Nuffield Council on Bioethics reaffirmed the importance of
      altruism in organ donation, and offered a clearer definition. This definition is,
      however, more permissive than that of altruism previously seen in UK policy, and
      as a result allows some donations that previously have been considered
      unacceptable. We argue that while altruistic motivation may be desirable, it is
      not necessary. 

PMID- 23538330
TI  - FY1 doctors' ethicolegal challenges in their first year of clinical practice: an
      interview study.
AB  - BACKGROUND: There is little evidence of junior trainee perspectives in the design
      and implementation of medical ethics and law (MEL) curriculum in UK medical
      schools. AIM: To determine the ethical issues the foundation year 1 (FY1) doctors
      (first year after graduation)  encountered during clinical practice and the
      skills and knowledge of MEL, which were useful in informing MEL curriculum
      development. METHOD: The National Research Ethics Service gave ethical approval.
      Eighteen one-to-one interviews were conducted in each school with FY1 doctors.
      ANALYSIS: Interviews were recorded and transcribed verbatim; a thematic analysis
      was undertaken with the transcriptions and saturation of themes was achieved. KEY
      FINDINGS: Themes closely overlapped between the two study sites. (1) Knowing my
      place as an FY1 (this theme consisted of four subthemes: challenging the
      hierarchy, being honest when the team is titrating the truth, taking consent for
      unfamiliar procedures and personal safety vs competing considerations); (2) Do
      not attempt resuscitation)/end-of-life pathway and its implications; (3) 'You
      have to be there' (contextualising ethics and law teaching through cases or role
      plays to allow students to explore future work situations); and (4) advanced
      interpersonal skills competency for ethical clinical practice. CONCLUSIONS: The
      data provide a snapshot of the real challenges faced by MEL FY1 doctors in early
      clinical practice: they may feel ill-prepared and sometimes unsupported by senior
      members of the team. The key themes suggest areas for development of
      undergraduate and postgraduate MEL curricula. We will work to develop our own
      curriculum accordingly. We intend to further investigate the applicability of our
      findings to UK medical ethics and law curriculum.

PMID- 23538331
TI  - Ultrathin polymeric coatings based on hydrogen-bonded polyphenol for protection
      of pancreatic islet cells.
AB  - Though transplantation of pancreatic islet cells has emerged as a promising
      treatment for Type 1 diabetes its clinical application remains limited due to a
      number of limitations including both pathogenic innate and adaptive immune
      responses. We report here on a novel type of multifunctional cytoprotective
      material applied to coat living pancreatic islets. The coating utilizes hydrogen
      bonded interactions of a natural polyphenol (tannic acid) with poly(N
      vinylpyrrolidone) deposited on the islet surface via non-ionic layer-by-layer
      assembly. We demonstrate that the coating is conformal over the surface of
      mammalian islets including those derived from rat, non-human primate (NHP), and
      human. In contrast to unmodified controls, the coated islets maintain their
      viability and beta-cell functionality for at least 96 hours in vitro. We also
      determine that the coating demonstrates immunomodulatory cytoprotective
      properties suppressing pro-inflammatory cytokine synthesis in stimulated bone
      marrow-derived macrophages and diabetogenic BDC-2.5 T cells. The coating material
      combines high chemical stability under physiologically relevant conditions with
      capability of suppressing cytokine synthesis, crucial parameters for prolonged
      islet integrity, viability, and function in vivo. Our study offers new
      opportunities in the area of advanced multifunctional materials to be used for a
      cell-based transplantation therapy.

PMID- 23538332
TI  - Population deviation of piggery-associated methicillin-resistant Staphylococcus
      aureus based on mec-associated direct repeat unit analysis.
AB  - Piggery-associated methicillin-resistant Staphylococcus aureus (MRSA) is a
      potential zoonotic pathogen. We constructed the population structure and dynamics
      of staphylococcal chromosome cassette mec (SCCmec) in MRSA ST9 isolates from
      different geographical areas of Taiwan. A total of 140 MRSA (135 piggery and 5
      human clinical) isolates from three populations located in western Taiwan (n=96
      including the 5 clinical isolates), central eastern Taiwan (n=22), and Penghu
      Island (n=22) were collected and characterized by analysis of the mec-associated
      direct repeat unit (dru). Twenty-eight dru types (with 24 novel) and 15 dru
      Clonal Complexes (CCs) were identified. The predominant novel dt12w type (48.6%)
      was widespread in all populations and may have a superior ability to transmit
      among populations. The minimum spanning network showed that at least two
      ancestral dru types (dt11a and dt12w) were identified, and the genetics between
      different populations could be differentiated. Temporal distributions of clone
      population dynamics estimated through the Bayesian skyline plot indicated a
      stable population with a long evolutionary history for MRSA ST9 in Taiwan.
      Findings indicating that some dru types are shared between piggery-associated and
      human-clinical MRSA ST9 suggest the occurrence of cross-species horizontal
      transmission of SCCmec.

PMID- 23538333
TI  - Polymorphisms in the SUFU gene are associated with organ injury protection and
      sepsis severity in patients with Enterobacteriacea bacteremia.
AB  - BACKGROUND: Organ injury including acute kidney injury (AKI) and acute lung
      Injury (ALI) are major contributors to mortality and morbidity in the setting of
      sepsis. Hedgehog pathway has been recognized as an important mediator in repair
      of organ injury. There are some clinical predictors associated with the
      development of organ injury in sepsis; however few host genetic risk factors have
      been identified and candidate genes for organ injury susceptibility and severity
      are largely unknown. METHODS: A prospective cohort study in a tertiary care
      hospital included 250 adult hospitalized patients with Enterobacteriacea
      bacteremia. We selected a panel of 69 tagging SNPs for genes in the Hedgehog
      signaling pathway using the TagSNP functionality of the SNPInfo web server and
      designed a panel on the GoldenGate Veracode genotyping assay (Illumina). We
      confirmed Illumina data using Taqman allelic discrimination assays. We assessed
      SNPs in combination with clinical variables for associations with outcomes and
      organ injury. RESULTS: Significant associations were identified using logistic
      regression models, controlling for age, race and gender. From the 69 tagging
      SNPs, 5 SNPs were associated with renal function and 2 with APACHEII score after
      false discovery rate correction. After multivariate analysis SNPs rs10786691
      (p=0.03), rs12414407 (p=0.026), rs10748825 (p=0.01), and rs7078511 (p=0.006), all
      in the suppressor of fused homolog (SUFU) gene, correlated with renal function.
      Likewise, SUFU SNPs rs7907760 (p=0.009) and rs10748825 (p=0.029) were associated
      with APACHEII score. SNPs rs12414407 and rs1078825 are in linkage disequilibrium
      (LD) with rs2296590, a SNP in the 5'-UTR region that is within a predicted
      transcription factor bind site for CCAAT-enhancer-binding proteins. In
      multivariate analyses functional SNP rs2296590 was correlated with renal function
      (p=0.004) and APACHEII score (p=0.049). CONCLUSIONS: Host susceptibility factors
      play an important role in sepsis development and sepsis related organ injury.
      Polymorphisms in the SUFU gene (encoding for a negative regulator of the hedgehog
      signaling pathway) are associated with protection from Enterobacteriacea
      bacteremia related organ injury and sepsis severity.

PMID- 23538334
TI  - Genetic and functional evidence for a role for SLC11A1 in susceptibility to
      otitis media in early childhood in a Western Australian population.
AB  - Otitis media (OM) is a common disease in early childhood characterised by
      inflammation of the middle ear. Susceptibility to recurrent acute OM (rAOM; >=3
      episodes AOM in 6 months) and chronic OM with effusion (COME; middle ear effusion
      >=3 months) is 40-70% heritable. Three bacterial pathogens commonly associated
      with OM, Streptococcus pneumoniae (Sp), non-typeable Haemophilus influenzae
      (NTHi) and Moraxella catarrhalis (Mc), have been observed within adenoids and as
      facultative intracellular pathogens that invade and survive in mononuclear cells.
      Case/pseudo-control conditional logistic regression analysis of variants in the
      SLC11A1 gene, initially identified for its role in resistance to intra-macrophage
      pathogens in mice, revealed association with OM at four polymorphisms
      (Pbest=0.025) in 531 families (660 affected children) from the Western Australian
      Family Study of Otitis Media. This included association at the functional
      promoter GTn polymorphism (rs34448891) with alleles that regulate high (allele 3;
      odds ratio=1.2, 95% CI 1.00-1.44, P=0.04) versus low (allele 2; odds ratio=0.83,
      95% CI 0.69-0.99, P=0.04) SLC11A1 expression. Haplotype and stepwise conditional
      logistic regression analyses support a single genetic effect in the proximal
      region of SLC11A1, with the haplotype 3_C_C_G across
      rs34448891_rs2276631_rs3731865_rs2695343 significantly (P=0.008) over-transmitted
      to affected offspring. Stratified analysis showed no association with OM in
      children who had undergone adenoidectomy (296 children), whereas children with
      adenoids intact (364 children) showed improved significance at the GTn
      polymorphism (allele 3: odds ratio=1.38, 95% CI=1.10-1.75, P=0.006). Quantitative
      RT/PCR demonstrated high expression of SLC11A1 in mononuclear cells isolated from
      adenoid tissue, with a trend for decreased expression with increasing copies of
      GTn allele 2. Expression of SLC11A1 was enhanced at 12 (P=1.2*10(-3)) and 24h
      (P<1.0*10(-4)) after infection of Mono-Mac-6 cells with NTHi. This study
      identifies SLC11A1 as a novel candidate for OM susceptibility, particularly in
      children with adenoids intact. Further analysis in other cohorts is required to
      validate these observations.

PMID- 23538335
TI  - Phylogenetic analysis of G1P[6] group A rotavirus strains detected in Northeast
      Brazilian children fully vaccinated with RotarixTM.
AB  - In 2009 the World Health Organization recommended the use of group A rotavirus
      (RVA) vaccines in all national immunization programs (NIPs) in order to control
      severe RVA gastroenteritis disease. In Brazil, RotarixTM was introduced in the
      NIP in March 2006, and a significant reduction in mortality rates among children
      <= 5 years old was observed, especially in the Northern and Northeastern Brazil.
      In the current study the 11 gene segments of six Brazilian G1P[6] RVA strains,
      isolated in 2009 and 2010 from vaccinated children, were analyzed in order to
      investigate if the genetic composition of these strains might help to elucidate
      why they were able to cause acute gastroenteritis in vaccinated children. All six
      Brazilian RVA strains revealed a complete Wa-like genotype constellation: G1-P[6]
      I1-R1-C1-M1-A1-N1-T1-E1-H1. Phylogenetic analysis showed that all six strains
      were nearly identical and showed a close genetic relationship with contemporary
      typical human Wa-like RVA strains. These results suggests that the fact that
      these strains were able to cause acute gastroenteritis in vaccinated children is
      likely not due to the genetic background of the strains, but rather to other
      factors such as host relating factors, co-infecting pathogens or vaccine
      efficacy. P[6] RVA strains are detected rather occasionally in humans in most
      regions of the world, except for South Asia and Sub-Saharan Africa. However,
      recently two studies conducted in Brazil showed the circulation of G12P[6] and
      G2P[6]. This is the first report on the detection and complete genome analyses of
      G1P[6] RVA strains in Brazil. Surveillance studies will be crucial to further
      investigate the prevalence of this genotype in the Brazilian population, and the
      efficacy of current licensed vaccines, which do not contain the P[6] genotype.

PMID- 23538336
TI  - Hepatitis B virus subgenotyping: history, effects of recombination,
      misclassifications, and corrections.
AB  - Hepatitis B virus (HBV) has evolved into phylogenetically separable genotypes and
      subgenotypes. Accurately assigning the subgenotype for an HBV strain is of
      clinical and epidemiological significance. In this paper, we review the
      recommendations currently employed for HBV subgenotyping, the history of HBV
      subgenotyping, the effects of recombination on HBV subgenotyping,
      misclassifications in HBV subgenotyping, and suggestions are made to correct the
      misclassifications. Finally, proposals are made to guide future HBV
      subgenotyping.

PMID- 23538337
TI  - Development of an upwind sailing ergometer.
AB  - PURPOSE: To develop a sailing ergometer that accurately simulates upwind sailing
      exercise. METHODS: A sailing ergometer that measures roll moment accompanied by a
      biofeedback system that allows imposing a certain quasi-isometric upwind sailing
      protocol (ie, 18 bouts of 90-s hiking at constantly varying hiking intensity
      interspersed with 10 s to tack) was developed. Ten male high-level Laser sailors
      performed an incremental cycling test (ICT; ie, step protocol at 80 W + 40 W/3
      min) and an upwind sailing test (UST). During both, heart rate (HR), oxygen
      uptake (VO(2)), ventilation (V(E)), respiratory-exchange ratio, and rating of
      perceived exertion were measured. During UST, also the difference between the
      required and produced hiking moment (HM) was calculated as error score (ES). HR,
      VO(2), and V(E) were calculated relative to their peak values determined during
      ICT. After UST, the subjects were questioned about their opinion on the
      resemblance between this UST and real-time upwind sailing. RESULTS: An average HM
      of 89.0% +/- 2.2% HM(max) and an average ES of 4.1% +/- 1.8% HM(max) were found.
      Mean HR, VO(2), and V(E) were, respectively, 80% +/- 4% HR(peak), 39.5% +/- 4.5%
      VO(2peak), and 30.3% +/- 3.7% VE(peak). Both HM and cardiorespiratory values
      appear to be largely comparable to literature reports during on-water upwind
      sailing. Moreover, the subjects gave the upwind sailing ergometer a positive
      resemblance score. CONCLUSIONS: Results suggest that this ergometer accurately
      simulates on-water upwind sailing exercise. As such, this ergometer could be a
      great help in performance diagnostics and training follow-up.

PMID- 23538338
TI  - Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model
      identifies polymorphisms associated with outcome in AML patients.
AB  - A whole-genome approach was used to investigate the genetic determinants of
      cytarabine-induced cytotoxicity. We performed a meta-analysis of genome-wide
      association studies involving 523 lymphoblastoid cell lines (LCLs) from
      individuals of European, African, Asian, and African American ancestry. Several
      of the highest-ranked single-nucleotide polymorphisms (SNPs) were within the
      mutated in colorectal cancers (MCC) gene. MCC expression was induced by
      cytarabine treatment from 1.7- to 26.6-fold in LCLs. A total of 33 SNPs ranked at
      the top of the meta-analysis (P < 10(-5)) were successfully tested in a clinical
      trial of patients randomized to receive low-dose or high-dose cytarabine plus
      daunorubicin and etoposide; of these, 18 showed association (P < .05) with either
      cytarabine 50% inhibitory concentration in leukemia cells or clinical response
      parameters (minimal residual disease, overall survival (OS), and treatment
      related mortality). This count (n = 18) was significantly greater than expected
      by chance (P = .016). For rs1203633, LCLs with AA genotype were more sensitive to
      cytarabine-induced cytotoxicity (P = 1.31 * 10(-6)) and AA (vs GA or GG) genotype
      was associated with poorer OS (P = .015), likely as a result of greater treatment
      related mortality (P = .0037) in patients with acute myeloid leukemia (AML). This
      multicenter AML02 study trial was registered at www.clinicaltrials.gov as
      #NCT00136084.

PMID- 23538339
TI  - Novel homozygous VHL mutation in exon 2 is associated with congenital
      polycythemia but not with cancer.
AB  - Germline von Hippel-Lindau (VHL) gene mutations underlie dominantly inherited
      familial VHL tumor syndrome comprising a predisposition for renal cell carcinoma,
      pheochromocytoma/paraganglioma, cerebral hemangioblastoma, and endolymphatic sac
      tumors. However, recessively inherited congenital polycythemia, exemplified by
      Chuvash polycythemia, has been associated with 2 separate 3' VHL gene mutations
      in exon 3. It was proposed that different positions of loss-of-function VHL
      mutations are associated with VHL syndrome cancer predisposition and only C
      terminal domain-encoding VHL mutations would cause polycythemia. However, now we
      describe a new homozygous VHL exon 2 mutation of the VHL gene:(c.413C>T):P138L,
      which is associated in the affected homozygote with congenital polycythemia but
      not in her, or her-heterozygous relatives, with cancer or other VHL syndrome
      tumors. We show that VHL(P138L) has perturbed interaction with hypoxia-inducible
      transcription factor (HIF)1alpha. Further, VHL(P138L) protein has decreased
      stability in vitro. Similarly to what was reported in Chuvash polycythemia and
      some other instances of HIFs upregulation, VHL(P138L) erythroid progenitors are
      hypersensitive to erythropoietin. Interestingly, the level of RUNX1/AML1 and NF
      E2 transcripts that are specifically upregulated in acquired polycythemia vera
      were also upregulated in VHL(P138L) granulocytes.

PMID- 23538340
TI  - A homozygous telomerase T-motif variant resulting in markedly reduced repeat
      addition processivity in siblings with Hoyeraal Hreidarsson syndrome.
AB  - Hoyeraal Hreidarsson syndrome (HHS) is a form of dyskeratosis congenita (DC)
      characterized by bone marrow failure, intrauterine growth retardation,
      developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency, and
      extremely short telomeres. As with DC, mutations in genes encoding factors
      required for telomere maintenance, such as telomerase reverse transcriptase
      (TERT), have been found in patients with HHS. We describe 2 sibling HHS cases
      caused by a homozygous mutation (p.T567M) within the TERT T motif. This mutation
      resulted in a marked reduction in the capacity of telomerase to processively
      synthesize telomeric repeats, indicating a role for the T motif in this unique
      aspect of telomerase function. We support this finding by demonstrating defective
      processivity in the previously reported p.K570N T-motif mutation. The
      consanguineous, heterozygous p.T567M parents exhibited telomere lengths around
      the first percentile and no evidence of a DC phenotype. Although heterozygous
      processivity defects have been associated with familial, adult-onset pulmonary
      fibrosis, these cases demonstrate the severe clinical and functional impact of
      biallelic processivity mutations. Thus, despite retaining the capacity to add
      short stretches of telomeric repeats onto the shortest telomeres, sole expression
      of telomerase processivity mutants can lead to a profound failure of telomere
      maintenance and early-onset multisystem disease.

PMID- 23538341
TI  - Preapoptotic protease calpain-2 is frequently suppressed in adult T-cell
      leukemia.
AB  - Adult T-cell leukemia (ATL) is one of the most aggressive hematologic
      malignancies caused by human T-lymphotropic virus type 1 (HTLV-1) infection. The
      prognosis of ATL is extremely poor; however, effective strategies for diagnosis
      and treatment have not been established. To identify novel therapeutic targets
      and diagnostic markers for ATL, we employed focused proteomic profiling of the
      CD4(+)CD25(+)CCR4(+) T-cell subpopulation in which HTLV-1-infected cells were
      enriched. Comprehensive quantification of 14 064 peptides and subsequent 2-step
      statistical analysis using 29 cases (6 uninfected controls, 5 asymptomatic
      carriers, 9 HTLV-1-associated myelopathy/tropical spastic paraparesis patients, 9
      ATL patients) identified 91 peptide determinants that statistically classified 4
      clinical groups with an accuracy rate of 92.2% by cross-validation test. Among
      the identified 17 classifier proteins, alpha-II spectrin was drastically
      accumulated in infected T cells derived from ATL patients, whereas its digestive
      protease calpain-2 (CAN2) was significantly downregulated. Further cell cycle
      analysis and cell growth assay revealed that rescue of CAN2 activity by
      overexpressing constitutively active CAN2 (Delta(19)CAN2) could induce remarkable
      cell death on ATL cells accompanied by reduction of alpha-II spectrin. These
      results support that proteomic profiling of HTLV-1-infected T cells could provide
      potential diagnostic biomarkers and an attractive resource of therapeutic targets
      for ATL.

PMID- 23538342
TI  - Encapsulating peritoneal sclerosis: common or rare in peritoneal dialysis?
AB  - Encapsulating peritoneal sclerosis (EPS) is a serious and often fatal
      complication of long-term peritoneal dialysis (PD) with severe malnutrition and
      poor prognosis. It causes progressive obstruction and encapsulation of the bowel
      loops. As EPS becomes more prevalent with longer duration of PD, large
      multicenter prospective studies are needed to establish its incidence and
      identify risk factors, therapeutic approach, and prognosis.

PMID- 23538343
TI  - Autosomal dominant polycystic kidney disease: new insights into treatment.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the world's most common
      inherited kidney disease. An increasing number of animal and human studies have
      enhanced our understanding of the molecular and cellular pathology of ADPKD. New
      treatment options are being tested in clinical trials in spite of the failure of
      mammalian target of rapamycin inhibitor therapy. The main and most effective
      therapy remains control of hypertension by renin-angiotensin-aldosterone system
      (RAAS) blockade. This review focuses only on promising therapies, including dual
      inhibition of RAAS, vasopressin receptor antagonists, increased fluid intake, and
      blockade of certain receptors of cyclic adenosine monophosphate. Also, the paper
      reviews what these advances mean to patients and clinicians and elaborates on how
      these changes can be immediately applied to clinical practice. There is an urgent
      need for discovery of new therapies targeted toward ADPKD in comparison with
      therapeutic progress of all other renal diseases.

PMID- 23538344
TI  - Post-transplantation lymphoproliferative disorders (PTLD) localized in the
      central nervous system: report from an international survey on PTLD.
AB  - Post-transplantation lymphoproliferative disorders (PTLD) localized to the
      central nervous system (CNS) is a rare but potentially fatal side-effect of
      immunosuppression for organ transplantation. Till now, to the best of our
      knowledge, the total number of such cases reported worldwide is less than 100. In
      this survey, we collected the data of PTLD localized to the CNS (CNS-PTLD) and
      compared this data with other PTLD patients with localizations to other areas
      serving as the control group. A comprehensive search was performed for studies
      reporting CNS-PTLD data in the Pubmed and Google scholar search engines. Finally,
      international data from 21 different studies were included in the analysis.
      Overall, 367 patients were entered into analysis. Organ recipients with CNS-PTLD
      had comparable gender make up, lymphoma cell types, Epstein-Barr virus infection
      rate, remission and mortality rates, with PTLD patients having other
      localizations. Multiorgan involvement as well as disseminated lymphoma were
      significantly more prevalent in the control group (P <0.05). At the last follow
      up, 192 (60%) patients were dead (47 missing data). Irrespective of whether the
      overall death or only death due to PTLD was used as the final outcome, we found
      that the survival rates were similar for patients of the two groups (P = 0.895).
      Renal transplant recipients are at greater risk for developing CNS involvement by
      PTLD, while heart and liver recipients represent significant lower risks for the
      same. This study showed that PTLD patients who had CNS presentation have quite a
      comparable outcome compared with those with other areas of localization. However,
      further prospective studies are needed for reaffirming our findings.

PMID- 23538345
TI  - Risk factors and consequences of delayed graft function.
AB  - The impact of delayed graft function (DGF) on the outcome of renal
      transplantation remains controversial. We analyzed the risk factors for DGF and
      its impact on graft and patient survival. A total of 354 renal transplants
      performed between June 1986 and April 2000 were analyzed. Variables analyzed
      included donor and recipient age, method and duration of renal replacement
      therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute
      rejection, length of stay in the hospital, serum creatinine at the end of first
      hospitalization as well as graft and patient survival at one, three, five and ten
      years. The study patients were divided into two groups: patients with DGF (G1)
      and those without DGF (G2). DGF occurred in 50 patients (14.1%), and it was seen
      more frequently in patients transplanted from deceased donors (60% vs. 40%, P
      <0.0001). The cause of DGF was acute tubular necrosis, seen in 98% of the cases.
      Univariate analysis showed a statistically significant difference between the two
      groups G1 and G2 in the following parameters: average duration on dialysis (52.3
      vs. 36.4 months, P = 0.006), HLA mismatch (44.9% vs. 32.11% P = 0.015), donor age
      (35.9 vs. 40.2 years, P = 0.026), cold ischemia time (23 vs. 18.2 h, P = 0.0016),
      warm ischemia time (41.9 vs. 38.6 mn, P = 0.046), length of stay in the hospital
      during first hospitalization (54.7 vs. 33.2 days, P <0.0001), serum creatinine at
      the end of first hospitalization (140 vs. 112 MUmol/L, P <0.0001) and at three
      months following transplantation (159 vs. 119 MUmol/L, P = 0.0002). Multivariate
      analysis revealed the following independent risk factors for DGF: deceased donor
      (RR = 13.2, P <0.0001) and cold ischemia time (RR = 1.17, P = 0.008). The graft
      survival at one, three, five and ten years was 100%, 93%, 88.3% and 78.3% in G1
      versus 100%, 95.9% 92.8% and 82.3% in G2; there was no statistically significant
      difference. The patient survival at one, three, five and ten years was 100%,
      91.3%, 83.6% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 with a
      statistically significant difference (P = 0.04). Prolonged cold ischemia time and
      transplantation of kidneys from deceased donors were the main risk factors for
      DGF in our study. Also, DGF significantly affected patient survival but had no
      influence on graft survival.

PMID- 23538346
TI  - The new technique of using the epigastric arteries in renal transplantation with
      multiple renal arteries.
AB  - The most common anatomic variant seen in the donor kidneys for renal
      transplantation is multiple renal arteries (MRA), which can cause an increased
      risk of complications. We describe the long-term outcomes of 16 years of
      experience in 76 kidney transplantations with MRAs. In a new reconstruction
      technique, we remove arterial clamps after anastomosing the donor to the
      recipient's main renal vessels, which cause backflow from accessory arteries to
      prevent thrombosis. By this technique, we reduce the ischemic times as well as
      the operating times. Both in live or cadaver donor kidneys, lower polar arteries
      were anastomosed to the inferior epigastric artery and upper polar arteries were
      anastomosed to the superior epigastric arteries. Injection of Papaverine and
      ablation of sympathic nerves of these arteries dilate and prevent them from post
      operative spasm. Follow-up DTPA renal scan in all patients showed good perfusion
      and function of the transplanted kidney, except two cases of polar arterial
      thrombosis. Mean creatinine levels during at least two years of follow-up
      remained acceptable. Patient and graft survival were excellent. No cases of ATN,
      hypertension, rejection and urologic complications were found. In conclusion,
      this technique can be safely and successfully utilized for renal transplantation
      with kidneys having MRAs, and may be associated with a lower complication rate
      and better graft function compared with the existing techniques.

PMID- 23538347
TI  - Predictors of quality of life in hemodialysis patients.
AB  - Quality of Life (QoL) is a consistent and powerful predictor that affects the out
      come in end-stage renal disease (ESRD) patients on dialysis. This study was
      undertaken to identify the factors that might predict QoL scores among ESRD
      patients on hemodialysis (HD). The study was conducted at three HD units in Saudi
      Arabia from January 2007 to January 2008. We studied 100 HD patients (53 males
      and 47 females) and used the SF-36 and KDQoL-SF forms covering six domains of
      QoL, namely physical, emotional, social, illness impact, medical and financial
      satisfaction, and overall general health. The mean age of the study patients was
      47.5 +/- 13.8 years and the mean duration of dialysis was 77.2 +/- 75.5 months.
      The QoL scores were 45.8 +/- 17.1 for general health, 53.1 +/- 32.0 for physical
      QoL, 50.5 +/- 14.8 for emotional QoL, 54.9 +/- 18.1 for social QoL, 46.5 +/- 13.7
      for illness impact, and 45.9 +/- 12.2 for the medical and financial domain. The
      total QoL score was 49.5 +/- 13.7. The male patients had statistically
      significantly reduced QoL and younger patients had better QoL scores. The QoL
      scores revealed a decreasing trend with decreasing level of education; they were
      elevated among employed patients. Multiple linear regression analysis
      demonstrated that age, dialysis duration, and male sex were negative predictors
      of QoL score. We conclude from our study that QoL is reduced in all the health
      domains of HD patients. Older age, male gender, unemployment, and duration of
      dialysis adversely affected the QoL scores. Adequate management of some of these
      factors could influence patient outcomes.

PMID- 23538348
TI  - Glycated albumin versus glycated hemoglobin as glycemic indicator in hemodialysis
      patients with diabetes mellitus: variables that influence.
AB  - The significance of glycated albumin (GA) compared with casual plasma glucose
      (PG) and glycated hemoglobin (HbA1c) was evaluated as an indicator of the
      glycemic control state in hemodialysis (HD) patients with diabetes. In HD
      patients with diabetes (n = 25), the mean PG, GA and HbA1c levels were 192.9 + 23
      mg/dL, 278.8 + 43 MUmol/L and 5.9 + 0.5%, respectively, which were higher by
      43.9%, 67.04% and 18%, respectively, compared with HD patients without diabetes
      (n = 25). HbA1c levels were significantly lower than simultaneous PG and GA
      values in those patients in comparison with the three parameters in patients who
      had diabetes without renal dysfunction (n = 25). A significant negative
      correlation was found between GA and serum albumin (r = 0.21, P <0.05) in HD
      patients with diabetes, whereas HbA1c correlated positively and negatively with
      hemoglobin (r = 0.11, P <0.01) and weekly dose of erythropoietin injection (r = 
      0.19, P < 0.01), respectively. Although PG and GA did not differ significantly
      between HD patients with diabetes and with and without erythropoietin injection,
      HbA1c levels were significantly higher in patients without erythropoietin.
      Categorization of glycemic control into arbitrary quartiles by GA level led to
      better glycemic control in a significantly higher proportion of HD patients with
      diabetes than those assessed by HA1c. Multiple regression analysis demonstrated
      that hemoglobin in addition to PG emerged as an independent factor associated
      with HbA1c in HD patients with diabetes, while PG, body mass index and albumin
      were an independent factor associated with GA. CONCLUSION: it is suggested that
      GA provides a significantly better measure to estimate glycemic control in HD
      patients with diabetes and that the assessment of glycemic control by HbA1c in
      these patients might lead to likely underestimation as a result of the increasing
      proportion of young erythrocyte by the use of erythropoietin.

PMID- 23538349
TI  - The clinical factors' prediction of increased intradialytic QT dispersion on the
      electrocardiograms of chronic hemodialysis patients.
AB  - Ventricular arrhythmias and sudden death are common in patients on maintenance
      hemodialysis (HD). The increase in QT dispersion (QTd) on the electrocardiogram
      (ECG) reflects increased tendency for ventricular repolarization that predisposes
      to arrhythmias. The purpose of the study was to identify the clinical factors
      that may predict the increased intradialytic QTd and to assess differences in QTd
      before and after HD. Each of 61 chronic HD patients underwent 12-lead ECG and
      blood pressure (BP) measurement before and every 1 h during a single HD session.
      The QT intervals were corrected for heart rate using Bazett's formula.
      Intradialytic QTd increased in 30 (49%) patients. There was no correlation
      between the increased QTd and the clinical factors including hypertension, pulse
      pressure, intradialytic hypotension, left ventricular hypertrophy, old myocardial
      infarct, diabetes mellitus, and nutritional status. The means of QT interval and
      QTd increased after HD session (from 382 +/- 29 to 444 +/- 26 ms, P <0.05; and
      from 74 +/- 21 to 114 +/- 53 ms, respectively, P <0.05). We conclude that the
      increased intradialytic QTd could not be predicted by any of the clinical factors
      evaluated in this study. There was significant difference in the means of QTd
      before and after HD session.

PMID- 23538350
TI  - Prevalence of hyponatremia among patients who used indapamide and
      hydrochlorothiazide: a single center retrospective study.
AB  - Hyponatremia is the most frequently encountered electrolyte abnormality among
      hospitalized patients and thiazide users. In this large single-center
      retrospective study, we aim to determine the prevalence and risk factors of
      hyponatremia among patients at the King Abdulaziz Medical City (KAMC), Riyadh,
      Saudi Arabia.To the best of our knowledge, this is the first such study in Saudi
      Arabia. A chart review was done for the years 2011-2012 of all admitted Saudi
      patients at KAMC who were treated with indapamide and hydrochlorothiazide. A
      total of 2000 patients were included [1237 females (629 indapamide and 608
      hydrochlorothiazide) and 762 males (371 indapamide and 391 hydrochlorothiazide)].
      Majority of the patients had type-2 diabetes mellitus (T2DM) with an overall
      prevalence of 72.2%. The overall prevalence of hyponatremia, regardless of
      severity, in the indapamide group was 37.3% versus 38.7% in the
      hydrochlorothiazide group. Stratification for age revealed that older patients
      had relatively higher levels of sodium (Na) as compared with younger patients,
      and this inverse association was significant (R = - 0.123; P <0.001). Increasing
      age, female gender and presence of T2DM were the significant risk factors for
      hyponatremia, explaining the 4.7% of the variance perceived (P <0.001). Our study
      suggests that the prevalence of hyponatremia among Saudi thiazide users is
      relatively high, and more so for the elderly and for those with T2DM. Early
      identification of this condition is important and caution should be exercised
      while prescribing thiazide drugs, particularly to those who are most at risk of
      developing hyponatremia to prevent related complications.

PMID- 23538351
TI  - Glomerular filtration barrier in pediatric idiopathic nephrotic syndrome.
AB  - Nephrotic syndrome (NS) is a common proteinuric disorder with defect in the perm
      selectivity of the glomerular filtration barrier (GFB). Ultrastructural
      morphometric evaluation of the GFB in pediatric NS has been attempted in only a
      few studies. This study was aimed at qualitative and quantitative evaluation of
      the alterations involving the GFB in pediatric idiopathic NS with an attempt to
      correlate these alterations with the clinico-laboratory data. For this study,
      renal biopsies from nine patients with NS and two children with interstitial
      nephritis were included. Relevant clinical and laboratory data, including degree
      of 24-h proteinuria and renal function tests, were recorded. Renal biopsies were
      reviewed for morphologic and electron microscopic diagnosis. Ultrastructural
      morphometry of the GFB was performed using image analysis software. The age at
      onset of NS, duration of illness, presence of hypertension, and renal function
      tests were comparable between the group of patients with minimal change disease
      (MCD) and those with mesangioproliferative glomerulonephritis (mesPGN)/focal
      segmental glomerulosclerosis (FSGS). However, the latter group showed higher 24-h
      proteinuria compared with the group with MCD. Among the detected ultra-structural
      changes, glomerular basement membrane thickness and foot process width were
      significantly different between the MCD and the mesPGN/FSGS groups. The slit pore
      diameter in the glomeruli showed a positive correlation with the degree of
      proteinuria. We conclude that our study demonstrated remarkable differences in
      certain parameters and the glomerular ultrastructural alterations in the various
      categories of NS. These differences might underlie the observed variation in
      response of these entities to various therapies.

PMID- 23538352
TI  - Pseudo-bartter syndrome, pattern and correlation with other cystic fibrosis
      features.
AB  - Pseudo-Bartter Syndrome (PBS), although quite common in patients with cystic
      fibrosis (CF), is often missed as simple dehydration or Bartter syndrome. This
      study was performed in patients with PBS to compare the pattern and course of the
      disease with those with CF not manifesting with this syndrome. All patients with
      CF who attended the respiratory clinic at Queen Rania Al-Abdallah Hospital from
      January 2000 to April 2010 were included in this retrospective case-control
      study. A specially formulated data sheet was used and those with PBS and those
      not having the syndrome were identified. A total of 110 patients (51% female)
      with CF with a median age of seven years were followed-up. Eighteen (16.3%) of
      them had one or more episodes of PBS. The median follow-up period was 6.2 years.
      All the episodes occurred during summer and in infancy. Median age of the initial
      episode of PBS was three months. One-third of them were initially followed at the
      nephrology clinic. Three patterns of PBS were identified: single episode in three
      (16.6%) patients, recurrent in 12 (66.6%) patients and chronic in three (16.6%)
      patients. Early colonization of Pseudomonas spp before 1 st birthday was seen in
      44% patients with PBS compared with 12% in other CF patients (P-value = 0.0075).
      The total number of colonized patients and other CF features at the time of the
      study did not differ significantly among patients, although the mean Shwachman
      Kulczycki score is significantly lower in those with recurrent PBS (69 compared
      with 85 in other CF patients). Gene mutation was identified in only 30% of the
      entire cohort. PBS is common in patients with CF, and it should be kept in mind
      in any patient with hypotonic dehydration and metabolic alkalosis. Recurrent
      pattern is associated with earlier Pseudomonas colonization.

PMID- 23538353
TI  - Value of sonography in the diagnosis of mild, moderate and severe vesicoureteral
      reflux in children.
AB  - This study was conducted to determine the positive predictive value (PPV) of gray
      scale sonography in the diagnosis of mild, moderate and severe vesicoureteral
      reflux (VUR). This cross-sectional descriptive analytic study was conducted in
      the University Clinic of Isfahan University of Medical Sciences in 2008. The
      study was performed on children aged two to 12 years; female children with
      febrile urinary tract infection (UTI) and clinical suspicion of VUR and males
      with history of UTI and VUR who attended follow-up during the six months study
      period were selected. Non-cooperative patients were excluded from the study. A
      total of 90 patients were studied. The data gathering method was sequential. The
      following sonographic parameters were assessed in all the study patients: antero
      posterior pelvic diameter, distal ureteric diameter and stasis of urinary system,
      which were measured at rest and during and after the Valsalva maneuver. Also, the
      vesicoureteral junction distance and distance of vesicoureteral junction to the
      midline were measured on both sides at rest. We then referred them for
      radionuclide cystography (RNC) and the results of the two methods were compared.
      Data were analyzed with SPSS program and t-test and chi square formulas were
      used. The sensitivity of ultrasound in the diagnosis of VUR was 70.9% and the
      specificity was 51.4%. Thus, the PPV was 69.64% and the negative predictive value
      was 52.94%. Although the most definite diagnosis of VUR is made with micrurating
      cystoureterography or RNC, sonography may be used as the first step in evaluation
      for VUR, especially in high-grade VUR.

PMID- 23538354
TI  - Acute renal failure associated with malaria in children.
AB  - Acute renal failure is one of the serious complications of malaria with untoward
      consequences including increased risk of mortality. This study was conducted to
      evaluate the incidence, clinical features, course, outcome, and predictors of
      mortality of acute renal failure (ARF) in children with malaria in the pediatric
      general wards and intensive care unit of our medical center from 1 January 2009
      to 31 December 2009. Data of all children from 1 month to 12 years of age with
      confirmed malaria either on peripheral smear and/or OptiMal test were reviewed.
      Those suffering from ARF were selected for further study. Twelve (eight
      Plasmodium falciparum; three Plasmodium vivax, and one mixed infection) out of
      227 (5%) cases of confirmed malaria had ARF. In addition to ARF, most of the
      patients had at least one other manifestation of severe malaria. Nine (75%)
      patients recovered completely, while 3 (25%) died. Presence of associated
      cerebral malaria, hyperbilirubinemia, and disseminated intravascular coagulopathy
      (DIC) was a poor prognostic factor and predictor of mortality. In conclusion, ARF
      can complicate both P. falciparum and P. vivax malaria. Malarial ARF as an
      isolated complication has a good prognosis. The presence of multiorgan
      involvement and delayed diagnosis increases morbidity and mortality.

PMID- 23538355
TI  - Cytomegalovirus ischemic colitis and transverse myelitis in a renal transplant
      recipient.
AB  - We report a rare case of cytomegalovirus (CMV)-associated ischemic colitis and
      transverse myelitis (TM) occurring precociously after renal transplantation. A 57
      year-old male was transplanted with a cadaveric kidney on 5 June 2009. The
      patient was CMV seropositive and the donor was seronegative. Transplantation was
      followed shortly by TM, which resulted in paraplegia. The results of magnetic
      resonance imaging of the spinal cord showed abnormalities. Twenty days after
      transplantation, he developed abdominal pain with melena and was diagnosed as
      having CMV-associated ischemic colitis confirmed by colonoscopy and biopsy.
      Serological data and identification of the viral genome by polymerase chain
      reaction were confirmatory for CMV. Treatment consisted of intravenous
      ganciclovir, followed by polyvalent immunoglobulin. The outcome was favorable.
      Symptomatic CMV infection is relatively common among the renal transplant
      population. Early colonoscopy is beneficial for making a quick diagnosis and
      therefore helps to institute a prompt management of CMV colitis. Myelitis is less
      common in transplant recipients and diagnosis, therefore, was more difficult.

PMID- 23538356
TI  - Candida lung abscesses in a renal transplant recipient.
AB  - We herein report a renal allograft recipient five years post transplant who had
      bilateral lung abscesses. The abscess grew Candida tropicalis on bronchoalveolar
      lavage. The patient was administered amphotericin B, but succumbed to massive
      hemoptysis. The case highlights a fungal complication in renal transplant and
      need for early suspicion and prompt therapy.

PMID- 23538357
TI  - Renal transplant in a tuberous sclerosis patient with bilateral giant renal
      angiomyolipomas and concurrent renal carcinoma.
AB  - Co-existence of angiomyolipoma (AML) and renal cell carcinoma (RCC) in the same
      tumor mass is very rare and only eight cases have been reported. We present a
      case of a young female with tuberous sclerosis complex (TSC) with bilateral huge
      renal AMLs. Both tumors were removed, one of which revealed co-incidental RCC.
      She was subsequently successfully transplanted a kidney from her brother and is
      maintaining normal graft function eight months post-transplant. No recurrence or
      metastases of RCC has been detected till the last follow-up.

PMID- 23538358
TI  - Hemodialysis treatment on an adult patient with Down syndrome associated with
      ectopic right kidney chronic obstructive nephropathy and secondary amyloidosis.
AB  - In the present report, we describe an unusual case of an adult patient with Down
      syndrome and ectopic right kidney, who developed end-stage renal disease due to
      chronic obstructive nephropathy and secondary amyloidosis and was successfully
      treated with hemodialysis.

PMID- 23538359
TI  - Delayed compartment syndrome following brachiocephalic arteriovenous fistula
      formation in a hemodialysis patient.
AB  - Delayed compartment syndrome following the surgical creation of an arteriovenous
      fistula (AVF) for vascular access is rare. A 71-year-old male patient experienced
      left anterior forearm compartment syndrome caused by a brachiocephalic AVF. The
      fistula failed after five days. Immediate radiological de-clotting failed and the
      thrombosed fistula was de-clotted with the help of a Fogarty balloon. On Day 11,
      the patient developed symptoms and signs of acute anterior forearm compartment
      syndrome and underwent immediate surgical decompression of the superficial and
      deep flexor compartments, which resulted in an excellent outcome. Iatrogenic
      forearm compartment syndrome is a rare but potential complication after creation
      of AVF. The critical errors regarding compartment syndrome are failure to
      recognize or failure to act. This case report illustrates that swift diagnosis
      and immediate surgical intervention results in an excellent outcome and avoids
      the morbidity associated with this potentially devastating and debilitating
      process.

PMID- 23538360
TI  - Rhabdomyolysis and acute renal failure following prolonged surgery in the
      lithotomy position.
AB  - Operative positions commonly used in urogenital surgeries when perineal exposure
      is required include the lithotomy and the exaggerated lithotomy positions (LPs),
      which expose patients to the risk of rhabdomyolysis. We report a patient with
      bladder outflow obstruction, benign prostatic hypertrophy and a very large
      bladder stone, which was removed with cystoscopy and cystolitholapaxy in the LP.
      The procedure was complicated by posterior bladder perforation and abdominal
      distention leading to prolonged surgery duration (5.5 h). The patient developed
      rhabdomyolysis and acute renal failure (ARF) without compartmental syndrome. On
      the other hand, there was a potential role of glycine solution, used for bladder
      irrigation, in the appearance of ARF. Overall, our case shows that rhabdomyolysis
      and ARF can develop in operative positions, and duration of surgery is the most
      important risk factor for such complications.

PMID- 23538361
TI  - Crescentic glomerulonephritis developing in the course of idiopathic
      membranoproliferative glomerulonephritis.
AB  - Membranoproliferative glomerulonephritis (MPGN) is a rare cause of the nephrotic
      syndrome in adults and children. Though small focal crescents may be seen in up
      to 10% of cases of MPGN, the presence of more than 50% crescents (crescentic
      MPGN) is rare. Very few cases of crescentic transformation of MPGN, documented by
      subsequent renal biopsies, have been described in the literature. A young female
      patient underwent kidney biopsy for the nephrotic-nephritic syndrome and was
      diagnosed as idiopathic MPGN. She was administered immunosuppressive therapy
      (steroids and cyclophosphamide), with which her renal functions stabilized. Six
      months later, she presented with features suggestive of rapidly progressive renal
      failure and underwent a second renal biopsy. The second biopsy showed crescentic
      glomerulonephritis with immune complex deposition, suggestive of MPGN. A final
      diagnosis of crescentic transformation of MPGN was made. Crescentic
      transformation of MPGN is a rare occurrence, but needs to be considered in a
      patient diagnosed as MPGN and presenting with rapidly progressive renal failure.
      The cause of such transformation remains to be elucidated.

PMID- 23538362
TI  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC): report
      of three cases with a novel mutation in CLDN19 gene.
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a
      rare autosomal recessive disorder that is caused by mutation in the genes coding
      for tight junction proteins Claudin-16 and Claudin-19. Affected individuals
      usually develop nephrocalcinosis and progressive renal failure; some of them may
      have ophthalmologic involvement as well. Phenotypic description of three affected
      individuals from the same Middle Eastern kindred (two sisters and their cousin)
      is presented. This includes both clinical and laboratory findings upon initial
      presentation and subsequent follow-up. Molecular analysis of the CLDN19 gene was
      performed on the three cases and one set of parents. A novel homozygous missense
      mutation in CLDN19 (c.241C>T, p.Arg81Cys) was detected in all three affected
      children. The parents were heterozygous. Clinical and laboratory data in the
      three children with renal and ocular manifestations of FHHNC are described.
      Genetic analysis revealed a novel mutation in the CLDN19 gene. FHHNC is a rare
      cause of nephrocalcinosis, and we believe that it should be considered in the
      presence of nephrocalcinosis with hypercalcuria and hypermagnesuria.

PMID- 23538363
TI  - Acute kidney injury: global health alert.
AB  - Acute kidney injury (AKI) is increasingly prevalent in developing and developed
      countries and is associated with severe morbidity and mortality. Most etiologies
      of AKI can be prevented by interventions at the individual, community, regional
      and in-hospital levels. Effective measures must include community-wide efforts to
      increase an awareness of the devastating effects of AKI and provide guidance on
      preventive strategies, as well as early recognition and management. Efforts
      should be focused on minimizing causes of AKI, increasing awareness of the
      importance of serial measurements of serum creatinine in high risk patients, and
      documenting urine volume in acutely ill people to achieve early diagnosis; there
      is as yet no definitive role for alternative biomarkers. Protocols need to be
      developed to systematically manage prerenal conditions and specific infections.
      More accurate data about the true incidence and clinical impact of AKI will help
      to raise the importance of the disease in the community, increase awareness of
      AKI by governments, the public, general and family physicians and other health
      care professionals to help prevent the disease. Prevention is the key to avoid
      the heavy burden of mortality and morbidity associated with AKI.

PMID- 23538364
TI  - Knowledge translation through clinical pathways: principles for practical
      development and successful use.
AB  - Proper implementation of guidelines is clearly associated with better medical
      outcomes. Success of guidelines' implementation depends on the tools used to
      accomplish it. Clinical pathways, also known as Integrated Care Pathways,
      represent one such tool that clearly promotes the implementation of guidelines
      and research evidence into clinical practice. They also encourage
      multidisciplinary teamwork, help in staff education, and aid in clinical research
      and audit. Additionally, they help in cutting hospital care costs. Important
      steps for a successful pathway development and implementation include getting
      leadership support, involving relevant people, selecting the right area of
      practice, using multiple implementation strategies and regularly assessing and
      monitoring pathway implementation.

PMID- 23538365
TI  - Effect on early graft function of high-dose desmopressin in transplant recipients
      with bleeding disorders.

PMID- 23538366
TI  - The risk factors of anemia after kidney transplantation.

PMID- 23538367
TI  - Impact of hemodialysis session on endothelial function and oxidative stress -
      evaluation in maintenance hemodialysis.

PMID- 23538369
TI  - Deciphering Alport syndrome.

PMID- 23538368
TI  - Accidental placement of the continuous ambulatory peritoneal dialysis catheter
      into the urinary bladder.

PMID- 23538370
TI  - Renal school: Dubai experience.

PMID- 23538371
TI  - Inappropriate use of urinary catheter and its common complications in different
      hospital wards.

PMID- 23538372
TI  - Takayasu's arteritis presenting as renovascular hypertension.

PMID- 23538373
TI  - Pattern of glomerular diseases in Oman: a study based on light microscopy and
      immunofluorescence.
AB  - Light microscopy and immunofluorescence play an important part in the final
      diagnosis of renal biopsy. The aim of this study was to analyze the pattern of
      various glomerular diseases in Oman. A total of 424 renal biopsies were
      retrospectively analyzed at the Sultan Qaboos University Hospital between 1999
      and 2010. Focal and segmental glomerulosclerosis (FSGS), minimal change disease
      (MCD), membranous glomerulopathy (MGN) and IgA nephropathy were the most common
      primary glomerular diseases encountered, accounting for 21.2%, 17%, 12.3% and
      8.3%, respectively, of all cases. Lupus nephritis was the most common secondary
      glomerular disease and was the most prevalent among all biopsies, accounting for
      30.4% of all biopsies. Amyloidosis was seen in only two cases. The presence of
      fluorescein isothiocyanatefibrin in all renal cases was low when compared with
      IgG, IgA, IgM, C3 and C1q markers. In conclusion, based on the findings of this
      study, lupus nephritis was the most common of all glomerular diseases and FSGS
      was the most common primary glomerular disease. The importance of fluorescein
      isothiocyanate-fibrin in the diagnosis of renal biopsy needs to be further
      investigated.

PMID- 23538374
TI  - Progression of diabetic nephropathy, risk of end-stage renal disease and
      mortality in patients with type-1 diabetes.
AB  - Numerous studies have shown that diabetic nephropathy (DNP) is associated with an
      elevated risk of progression toward end-stage renal disease (ESRD) as well as
      increased cardiovascular mortality. The majority of these studies are from the
      developed countries. The factors leading to the progression of DNP may not be
      quite the same in the developing countries. The aim of this study was to evaluate
      the risk factors of progression toward ESRD and mortality among type-1 diabetes
      (T1D) patients with DNP in a developing country. This prospective study was
      conducted enrolling 72 patients with T1D in September 2006, including T1D
      patients with DNP defined as microalbuminuria, proteinuria, and/or renal failure,
      and following them up for five years. The mean age was 29.5+/-7.5 years with a
      mean duration of diabetes of 17 (11-20) years. At the time of enrollment, 43.1%
      had arterial hypertension, 69.4% had proliferative retinopathy, 44.4 had clinical
      neuropathy, 25% lived in rural areas, and 51.4% had macroalbuminuria. Progression
      toward ESRD was observed in 34.7% of cases. In multivariate analysis, diastolic
      blood pressure (P = 0.006) and blood hemoglobin (P = 0.003) were identified as
      the risk factors associated with ESRD. Death occurred in 18.3% of cases,
      including 92.3% on hemodialysis with a median hemodialysis duration of six (1-60)
      months. In multivariate analysis, the ESRD was identified as risk factor for
      death (P <0.001). DNP due to T1D remains a disease involving a heavy burden of
      morbi-mortality and is difficult to manage in a developing country because of the
      low socioeconomic level of patients and the lack of reliable epidemiological
      data.

PMID- 23538375
TI  - Outcome of deceased donor renal transplantation - a single-center experience from
      developing country.
AB  - Renal transplantation (RTx) is considered as the best therapeutic modality for
      patient suffering from end-stage renal disease (ESRD). Dearth of donor kidneys is
      a major problem everywhere, and deceased donor renal transplantation (DDRTx) is
      seen as at least a partial solution. Even so, DDRTx accounts for only less than
      4% of RTx in India. We report our 6-year single-center experience on DDRTx vis-a
      vis patient/graft survival, graft function in terms of serum creatinine (SCr),
      rejection episodes, and delayed graft function (DGF). Between January 2005 and
      March 2011, 236 DDRTx were performed. Majority of the donors were those with
      brain death due to road traffic/cerebrovascular accidents. The commonest
      recipient diseases leading to ESRD were chronic glomerulonephritis (42.8%),
      diabetes (12.7%), and hypertension (10.6%). Mean recipient age was 36.2 +/- 14.2
      years; 162 were males and 74 were females. Mean donor age was 45.3 +/- 17.13
      years; 144 were males and 92 were females. Mean dialysis duration pre
      transplantation was 18.5 +/- 2.5 months. All recipients received single-dose
      rabbit-anti-thymocyte globulin induction and steroids, calcinueurin inhibitor,
      and mycophenolate mofetil/azathioprine for maintenance immunosuppression. Delayed
      graft function was observed in 29.6% patients and 22% had biopsy-proven acute
      rejection. Over the mean follow-up of 2.18 +/- 1.75 years, patient and graft
      survival rates were 74.57% and 86.8%, respectively, with mean SCr of 1.42 +/-
      0.66 mg%. DDRTx achieves acceptable graft function with patient/graft survival,
      encouraging the use of this approach in view of organ shortage.

PMID- 23538376
TI  - Prevalence of hypertension in healthy school children in Pakistan and its
      relationship with body mass index, proteinuria and hematuria.
AB  - To determine the prevalence of high blood pressure (BP) in healthy school
      Pakistani children and its association with high body mass index (BMI),
      asymptomatic hematuria and proteinuria, we studied 661 public school children and
      measured their body weight, height and BP and urine dipstick for hematuria
      performed on a single occasion. Hypertension (BP >95 th centile) and pre
      hypertension (BP >90 th centile) were defined based on the US normative BP
      tables. Over-weight and obesity were defined according to the World Health
      Organization (WHO) classification of BMI. The mean age of the children was 14 +/-
      1.3 years. The mean BMI was 18.5 +/- 4.3 kg/m 2 . The majority (81.8%) of the
      children were found to be normotensive (BP <90 th centile). Pre-hypertension was
      observed in 15% and hypertension in 3% of the children. Overweight was observed
      in 7.7% and obesity in 1% of the children. The independent risk factors for
      hypertension and pre-hypertension were age of the child (RR 1.2 95% CI 1-1.4),
      gender (RR 2.0 for being female 95% CI 1-4.4), BMI >25 (RR for BMI b/w 25-30 =
      2.6, RR for BMI >30 = 4.3), positive urine dipstick for proteinuria (RR = 2.3 95%
      CI 0.7-7.7) and positive urine dipstick for hematuria (RR 1.0 95% CI 0.2-8.3).
      Hypertension in children is strongly correlated with obesity, asymptomatic
      proteinuria and hematuria. Community based screening programs for children should
      include BP recording, BMI assessment and urine dipsticks analysis and approach
      high-risk groups for early detection and lifestyle modifications.

PMID- 23538377
TI  - Acute renal failure in children in a tertiary care center.
AB  - In this retrospective study, records of all patients aged one month to 12 years
      who presented with acute renal failure (ARF) between May 2005 and August 2010
      were retrieved. Clinical details, biochemistry, need for renal replacement
      therapy (RRT), cause of ARF and outcome at discharge were recorded. During this
      period, 230 children presented with ARF; their median age at presentation was 30
      months (range: five-144 months); 120 (52.2%) were males. The causes of ARF were
      acute tubular necrosis (ATN) in 121 (52.6%), glomerular disorders in 5.7%,
      structural anomalies of the urinary tract in 9.6% and hemolytic uremic syndrome
      in 27 (11.7%). The mean duration of hospital stay was 17.8 +/- 7.6 days. RRT was
      required for 54 patients (23.6%); peritoneal dialysis in 49 and hemodialysis in
      five patients. Complete recovery was noted in 99 study patients (43.2%) and
      sequelae remained in 84 patients (36.7%). Forty-six patients (20.1%) with ARF
      died. ATN secondary to septicemia was the most common cause of ARF in our study.

PMID- 23538378
TI  - Bacteriological study and structural composition of staghorn stones removed by
      the anatrophic nephrolithotomic procedure.
AB  - This study was conducted to determine the composition of staghorn stones and to
      assess the proportion of infected stones as well as the correlation between
      infection in the stones and bacteria grown in urine. Samples of 45 consecutive
      stones removed through anatrophic nephrolithotomic procedures were taken from the
      operation site and samples of urine were obtained by simultaneous bladder
      catheterization. The frequency of infection in the stones and correlation between
      infection of stone and urine samples were determined with respect to the
      composition of the stones. Twenty-two males and 23 females, with respective mean
      ages of 48.3 +/- 15.6 years and 51 +/- 7.4 years, were studied. The stone and
      urine cultures yielded positive results in ten and 16 patients, respectively, of
      a total of 45 patients (22.2% and 35.5%, respectively). Calcium oxalate was the
      main constituent of staghorn stones, seen in 31 patients (68.8%), uric acid in 12
      patients (26.6%) and struvite and/or calcium phosphate in 11 patients (24.4%). In
      seven of ten stones with bacterial growth, bacteria were isolated from urine
      cultures as well, which accounted for a concordance rate of 70%. The bacteria
      grown in the stone were the cause of urinary tract infection (UTI) in 43.5% of
      the cases. Stone infection was significantly associated with UTI (OR = 6.47; 95%
      CI 1.43-31.7, P = 0.021) and presence of phosphate in the stones (OR = 18, 95% CI
      3.28-99.6, P = 0.0006). E. coli was the most common bacteria grown from the
      stones, and was isolated in 50% of the cases; Ureaplasma urealyticum was the most
      common organism causing UTI, grown in 62.5% of the urine samples. There was a
      high concordance rate between bacteria in the stones and urine. These findings
      indicate that the urine culture can provide information for selection of an
      appropriate anti-microbial agent for stone sterilization. In addition, preventing
      re-growth or recurrence of stones and treatment of post-surgical infections would
      be facilitated based on the results of the urine culture.

PMID- 23538379
TI  - Long-term safety and effectiveness of mechanical versus biologic aortic valve
      prostheses in older patients: results from the Society of Thoracic Surgeons Adult
      Cardiac Surgery National Database.
AB  - BACKGROUND: There is a paucity of long-term data comparing biological versus
      mechanical aortic valve prostheses in older individuals. METHODS AND RESULTS: We
      performed follow-up of patients aged 65 to 80 years undergoing aortic valve
      replacement with a biological (n=24 410) or mechanical (n=14 789) prosthesis from
      1991 to 1999 at 605 centers within the Society of Thoracic Surgeons Adult Cardiac
      Surgery Database using Medicare inpatient claims (mean, 12.6 years; maximum, 17
      years; minimum, 8 years), and outcomes were compared by propensity methods. Among
      Medicare-linked patients undergoing aortic valve replacement (mean age, 73
      years), both reoperation (4.0%) and endocarditis (1.9%) were uncommon to 12
      years; however, the risk for other adverse outcomes was high, including death
      (66.5%), stroke (14.1%), and bleeding (17.9%). Compared with those receiving a
      mechanical valve, patients given a bioprosthesis had a similar adjusted risk for
      death (hazard ratio, 1.04; 95% confidence interval, 1.01-1.07), higher risks for
      reoperation (hazard ratio, 2.55; 95% confidence interval, 2.14-3.03) and
      endocarditis (hazard ratio, 1.60; 95% confidence interval, 1.31-1.94), and lower
      risks for stroke (hazard ratio, 0.87; 95% confidence interval, 0.82-0.93) and
      bleeding (hazard ratio, 0.66; 95% confidence interval, 0.62-0.70). Although these
      results were generally consistent among patient subgroups, bioprosthesis patients
      aged 65 to 69 years had a substantially elevated 12-year absolute risk of
      reoperation (10.5%). CONCLUSIONS: Among patients undergoing aortic valve
      replacement, long-term mortality rates were similar for those who received
      bioprosthetic versus mechanical valves. Bioprostheses were associated with a
      higher long-term risk of reoperation and endocarditis but a lower risk of stroke
      and hemorrhage. These risks varied as a function of a patient's age and
      comorbidities.

PMID- 23538380
TI  - Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart
      transplantation in US children.
AB  - BACKGROUND: Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular
      assist device is superior to extracorporeal membrane oxygenation for bridge to
      heart transplantation. Published data are limited to 1 in 4 children who received
      the device as part of the US clinical trial. We analyzed outcomes for all US
      children who received the EXCOR to characterize device outcomes in an unselected
      cohort and to identify risk factors for mortality to facilitate patient
      selection. METHODS AND RESULTS: This multicenter, prospective cohort study
      involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular
      assist device at 47 centers from May 2007 through December 2010. Multiphase
      nonproportional hazards modeling was used to identify risk factors for early (<2
      months) and late mortality. Of 204 children supported with the EXCOR, the median
      duration of support was 40 days (range, 1-435 days). Survival at 12 months was
      75%, including 64% who reached transplantation, 6% who recovered, and 5% who were
      alive on the device. Multivariable analysis identified lower weight,
      biventricular assist device support, and elevated bilirubin as risk factors for
      early mortality and bilirubin extremes and renal dysfunction as risk factors for
      late mortality. Neurological dysfunction occurred in 29% and was the leading
      cause of death. CONCLUSIONS: Use of the Berlin Heart EXCOR has risen dramatically
      over the past decade. The EXCOR has emerged as a new treatment standard in the
      United States for pediatric bridge to transplantation. Three-quarters of children
      survived to transplantation or recovery; an important fraction experienced
      neurological dysfunction. Smaller patient size, renal dysfunction, hepatic
      dysfunction, and biventricular assist device use were associated with mortality,
      whereas extracorporeal membrane oxygenation before implantation and congenital
      heart disease were not.

PMID- 23538381
TI  - Physiological right ventricular adaptation in elite athletes of African and Afro
      Caribbean origin.
AB  - BACKGROUND: Regular, intensive exercise results in physiological biventricular
      cardiac adaptation. Ethnicity is an established determinant of left ventricular
      remodeling; black athletes (BAs) exhibit more profound LV hypertrophy than white
      athletes (WAs). Right ventricular (RV) remodeling has not been characterized in
      BAs, although the issue is pertinent because BAs commonly exhibit ECG anomalies
      that resemble arrhythmogenic RV cardiomyopathy. METHODS AND RESULTS: Between 2006
      and 2012, 300 consecutive BAs (n=243 males) from 25 sporting disciplines were
      evaluated by use of ECG and echocardiography. Results were compared with 375 WAs
      and 153 sedentary control subjects (n=69 blacks). There were no ethnic
      differences between RV parameters in control subjects. Both BAs and WAs exhibited
      greater RV dimensions than control subjects. RV dimensions were marginally
      smaller in BAs than in WAs (proximal outflow tract, 30.9+/-5.5 versus 32.8+/-5.3
      mm, P<0.001; longitudinal dimension, 86.6+/-9.5 versus 89.8+/-9.6 mm, P<0.001),
      although only 2.3% of variation was attributable to ethnicity. RV enlargement
      compatible with diagnostic criteria for arrhythmogenic RV cardiomyopathy was
      frequently observed (proximal outflow tract >=32 mm; 45.0% of BAs, 58.5% of WAs).
      Anterior T-wave inversion was present in 14.3% of BAs versus 3.7% of WAs
      (P<0.001). Marked RV enlargement with concomitant anterior T-wave inversion was
      observed in 3.0% of BAs versus 0.3% of WAs (P=0.005). Further investigation did
      not diagnose arrhythmogenic RV cardiomyopathy in any athlete. CONCLUSIONS:
      Physiological RV enlargement is commonly observed in both black and white
      athletes. The impact of ethnicity is minimal, which obviates the need for race
      specific RV reference values. However, in the context of frequent ECG
      repolarization anomalies in BAs, the potential for erroneous diagnosis of
      arrhythmogenic RV cardiomyopathy is considerably greater in this ethnic group.

PMID- 23538382
TI  - The heart of an athlete: black, white, and shades of grey with no gold standard.

PMID- 23538383
TI  - Teaching Object-Picture Matching to Improve Concordance between Object and
      Picture Preferences for Individuals with Developmental Disabilities: Pilot Study.
AB  - We evaluated teaching object-picture matching to improve concordance between
      preference assessments using objects and pictures of the same objects. Three
      participants with developmental disabilities who showed high and low preferences
      during assessments with objects but not with pictures were taught object-picture
      matching tasks unrelated to the items used during preference assessments.
      Training was evaluated in a modified multiple-baseline design and preference
      assessments with objects and pictures were repeated after training each object
      picture matching task. Two participants showed improved concordance after
      mastering two and three training tasks, respectively. The third participant did
      not show concordance between object and picture preference assessments after
      mastering two tasks and after additional training. Our findings suggested that
      object-picture matching might be a prerequisite for picture preference
      assessments.

PMID- 23538384
TI  - Sugar promotes vegetative phase change in Arabidopsis thaliana by repressing the
      expression of MIR156A and MIR156C.
AB  - Nutrients shape the growth, maturation, and aging of plants and animals. In
      plants, the juvenile to adult transition (vegetative phase change) is initiated
      by a decrease in miR156. In Arabidopsis, we found that exogenous sugar decreased
      the abundance of miR156, whereas reduced photosynthesis increased the level of
      this miRNA. This effect was correlated with a change in the timing of vegetative
      phase change, and was primarily attributable to a change in the expression of two
      genes, MIR156A and MIR156C, which were found to play dominant roles in this
      transition. The glucose-induced repression of miR156 was dependent on the
      signaling activity of HEXOKINASE1. We also show that the defoliation-induced
      increase in miR156 levels can be suppressed by exogenous glucose. These results
      provide a molecular link between nutrient availability and developmental timing
      in plants, and suggest that sugar is a component of the leaf signal that mediates
      vegetative phase change. DOI:http://dx.doi.org/10.7554/eLife.00260.001.

PMID- 23538385
TI  - Distribution of methionine-enkephalin in the minipig brainstem.
AB  - We have studied the distribution of immunoreactive cell bodies and axons are
      containing methionine-enkephalin in the minipig brainstem. Immunoreactive axons
      were widely distributed, whereas the distribution of perikarya was less
      widespread. A high or moderate density of axons containing methionine-enkephalin
      were found from rostral to caudal levels in the substantia nigra, nucleus
      interpeduncularis, nucleus reticularis tegmenti pontis, nucleus dorsalis raphae,
      nucleus centralis raphae, nuclei dorsalis and ventralis tegmenti of Gudden, locus
      ceruleus, nucleus sensorius principalis nervi trigemini, nucleus cuneatus
      externalis, nucleus tractus solitarius, nuclei vestibularis inferior and
      medialis, nucleus ambiguus, nucleus olivaris inferior and in the nucleus tractus
      spinalis nervi trigemini. Immunoreactive perikarya were observed in the nuclei
      centralis and dorsalis raphae, nucleus motorius nervi trigemini, nucleus
      centralis superior, nucleus nervi facialis, nuclei parabrachialis medialis and
      lateralis, nucleus ventralis raphae, nucleus reticularis lateralis and in the
      formatio reticularis. We have also described the presence of perikarya containing
      methionine-enkephalin in the nuclei nervi abducens, ruber, nervi oculomotorius
      and nervi trochlearis. These results suggest that in the minipig the pentapeptide
      may be involved in many physiological functions (for example, proprioceptive and
      nociceptive information; motor, respiratory and cardiovascular mechanisms).

PMID- 23538386
TI  - Isolated tumour cells and micrometastases in intraductal breast cancer: a simple
      mechanical question in some cases.

PMID- 23538387
TI  - A short-term colorectal cancer sphere culture as a relevant tool for human cancer
      biology investigation.
AB  - BACKGROUND: Ex vivo colospheres have been previously characterised as a
      colorectal cancer (CRC) well-rounded multicellular model, exclusively formed by
      carcinoma cells, and derived from fresh CRC tissue after mechanical dissociation.
      The ability to form colospheres was correlated with tumour aggressiveness. Their
      three-dimensional conformation prompted us to further investigate their potential
      interest as a preclinical cancer tool. METHODS: Patient-derived CRC xenografts
      were used to produce numerous colospheres. Mechanism of formation was elucidated
      by confocal microscopy. Expression analysis of a panel of 64 selected cancer
      related genes by real-time qRT-PCR and hierarchical clustering allowed comparison
      of colospheres with parent xenografts. In vitro and in vivo assays were performed
      for migration and chemosensitivity studies. RESULTS: Colospheres, formed by
      tissue remodelling and compaction, remained viable several weeks in floating
      conditions, escaping anoikis through their strong cell-cell interactions.
      Colospheres matched the gene expression profile of the parent xenograft tissue.
      Colosphere-forming cells migrated in collagen I matrix and metastasised when
      subrenally implanted in nude mice. Besides, the colosphere responses to 5
      fluorouracil and irinotecan, two standard drugs in CRC, reproduced those of the
      in vivo original xenografts. CONCLUSION: Colospheres closely mimic biological
      characteristics of in vivo CRC tumours. Consequently, they would be relevant ex
      vivo CRC models.

PMID- 23538388
TI  - Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070.
AB  - BACKGROUND: Despite intensive research and novel adjuvant therapies, there is
      currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls
      metastasis to sites such as the liver; however, the therapeutic blockade with the
      existing agents has proven difficult. METHODS: AMD11070, a novel orally
      bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the
      migration of melanoma cells compared with the commonly described antagonist
      AMD3100. RESULTS: AMD11070 abrogated melanoma cell migration and was
      significantly more effective than AMD3100. Importantly for the clinical context,
      the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070.
      CONCLUSION: Liver-resident myofibroblasts excrete CXCL12, which is able to
      promote the migration of CXCR4-expressing tumour cells from the blood into the
      liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic
      strategy for both B-RAF wild-type and mutated melanomas.

PMID- 23538389
TI  - Reply: Isolated tumour cells and micrometastases in intraductal breast cancer: a
      simple mechanical question in some cases.

PMID- 23538391
TI  - Air pollution and heart failure: Relationship with the ejection fraction.
AB  - AIM: To study whether the concentrations of particulate matter in ambient air are
      associated with hospital admission due to heart failure in patients with heart
      failure with preserved ejection fraction and reduced ejection fraction. METHODS:
      We studied 353 consecutive patients admitted into a tertiary care hospital with a
      diagnosis of heart failure. Patients with ejection fraction of >= 45% were
      classified as having heart failure with preserved ejection fraction and those
      with an ejection fraction of < 45% were classified as having heart failure with
      reduced ejection fraction. We determined the average concentrations of different
      sizes of particulate matter (< 10, < 2.5, and < 1 MUm) and the concentrations of
      gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone)
      from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved
      ejection fraction population was exposed to higher nitrogen dioxide
      concentrations compared to the heart failure with reduced ejection fraction
      population (12.95 +/- 8.22 MUg/m(3) vs 4.50 +/- 2.34 MUg/m(3), P < 0.0001).
      Multivariate analysis showed that nitrogen dioxide was a significant predictor of
      heart failure with preserved ejection fraction (odds ratio ranging from (1.403,
      95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03).
      CONCLUSION: This study demonstrates that short-term nitrogen dioxide exposure is
      independently associated with admission in the heart failure with preserved
      ejection fraction population.

PMID- 23538390
TI  - microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer.
AB  - BACKGROUND: The purpose of this study was to identify prostate cancer (PC)
      oncogenic microRNAs (miRs) based on miR microarray and to investigate whether
      these oncogenic miRs may be useful as PC biomarkers. METHODS: Initially, we
      carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP
      cells. To investigate the function of miR-183, we used a miR-183 knockdown
      inhibitor in cell growth and wound-healing assays. We used several algorithms and
      confirmed that they are directly regulated by miR-183. RESULTS: We identified
      three potential oncogenic miRs (miR-146a, miR-183 and miR-767-5P). The expression
      of miR-183 in PC cells (PC-3, DU-145 and LNCaP) was upregulated compared with
      RWPE-1 cells. MiR-183 expression was also significantly higher in PC tissues
      compared with that in matched normal prostate tissues. Additionally, miR-183
      expression was correlated with higher prostate-specific antigen, higher pT and
      shorter overall survival. MiR-183 knockdown decreased cell growth and motility in
      PC cells and significantly decreased prostate tumour growth in in vivo nude mice
      experiments. We identified Dkk-3 and SMAD4 as potential target genes of miR-183.
      CONCLUSION: Our data suggest that oncogenic miR-183 may be useful as a new PC
      biomarker and that inhibition of miR-183 expression may be therapeutically
      beneficial as a PC treatment.

PMID- 23538392
TI  - A smartphone-based intervention with diaries and therapist feedback to reduce
      catastrophizing and increase functioning in women with chronic widespread pain.
      part 2: 11-month follow-up results of a randomized trial.
AB  - BACKGROUND: Internet-based interventions are increasingly used to support self
      management of individuals with chronic illnesses. Web-based interventions may
      also be effective in enhancing self-management for individuals with chronic pain,
      but little is known about long-term effects. Research on Web-based interventions
      to support self-management following participation in pain management programs is
      limited. OBJECTIVE: The aim is to examine the long-term effects of a 4-week
      smartphone-intervention with diaries and therapist-written feedback following an
      inpatient chronic pain rehabilitation program, previously found to be effective
      at short-term and 5-month follow-ups. METHODS: 140 women with chronic widespread
      pain, participating in a 4-week inpatient rehabilitation program, were randomized
      into two groups: with or without a smartphone intervention after the
      rehabilitation. The smartphone intervention consisted of one face-to-face
      individual session and 4 weeks of written communication via a smartphone,
      consisting of three diaries daily to elicit pain-related thoughts, feelings, and
      activities, as well as daily personalized written feedback based on cognitive
      behavioral principles from a therapist. Both groups were given access to an
      informational website to promote constructive self-management. Outcomes were
      measured with self-reported paper-and-pencil format questionnaires with
      catastrophizing as the primary outcome measure. Secondary outcomes included daily
      functioning and symptom levels, acceptance of pain, and emotional distress.
      RESULTS: By the 11-month follow-up, the favorable between-group differences
      previously reported post-intervention and at 5-month follow-up on
      catastrophizing, acceptance, functioning, and symptom level were no longer
      evident (P>.10). However, there was more improvement in catastrophizing scores
      during the follow-up period in the intervention group (M=-2.36, SD 8.41) compared
      to the control group (M=.40, SD 7.20), P=.045. Also, per protocol within-group
      analysis showed a small positive effect (Cohen's d=.33) on catastrophizing in the
      intervention group (P=.04) and no change in the control group from the smartphone
      intervention baseline to 11-month follow-up. A positive effect (Cohen's d=.73) on
      acceptance was found within the intervention group (P<.001) but not in the
      control group. Small to large negative effects were found within the control
      group on functioning and symptom levels, emotional distress, and fatigue (P=.05)
      from the intervention baseline to the 11-month follow-up. CONCLUSION: The long
      term results of this randomized trial are ambiguous. No significant between-group
      effect was found on the study variables at 11-month follow-up. However, the
      within-group analyses, comparing the baseline for the smartphone intervention to
      the 11-month data, indicated changes in the desired direction in catastrophizing
      and acceptance in the intervention group but not within the control group. This
      study provides modest evidence supporting the long-term effect of the
      intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT01236209;
      http://www.clinicaltrials.gov/ct2/show/NCT01236209 (Archived by WebCite at
      http://www.webcitation.org/6FF7KUXo0).

PMID- 23538393
TI  - Increasing efforts on vaccine preventable diseases in the EU.

PMID- 23538394
TI  - Dermatological manifestations and relationship to outcomes of patients admitted
      to a medical intensive care unit: a study from a tertiary care hospital in India.
AB  - AIM: To determine the prevalence of dermatological manifestations in intensive
      care unit (ICU) patients and assess its impact on outcomes. METHODS: This was a
      prospective cohort study of 1013 ICU patients admitted between December 2009 and
      April 2011. Patients were categorised following an initial screening (within 48
      h) and subsequent daily review as those with dermatological manifestations in
      association with multisystem disorder (category 1), occurring due to treatment or
      critical illness (category 2), coincidental lesions (category 3) or primary
      dermatological conditions needing intensive care (category 4). Outcomes included
      mortality, duration of ventilation and hospitalisation. Factors associated with
      mortality were explored using univariate and multivariate analyses. RESULTS:
      Dermatological manifestations were observed in 427 (42.2%) patients,
      predominantly of categories 1 (n=159) and 2 (n=160). Common aetiologies were
      infections (39.3%) and mechanical, thermal or physical injuries (32.8%). Primary
      dermatological conditions (n=33) included 21 patients with cutaneous infections,
      3 with angioedema, 2 each with pemphigus, toxic epidermal necrolysis and
      psoriasis, and 1 each with Stevens-Johnson syndrome, drug hypersensitivity
      syndrome and crusted scabies. The presence of cutaneous lesions increased
      mortality risk (OR 1.56, 95% CI 1.20 to 2.03) and significantly (p<0.001)
      prolonged ventilation and hospitalisation. Mortality was higher (p<0.001) in
      patients in categories 4 (65.6%) and 2 (57.5%) compared to those without
      manifestations (35.5%). After adjusting for age, Acute Physiology And Chronic
      Health Evaluation II (APACHE-II) score, ventilation and dialysis, the association
      between dermatological manifestations and mortality was insignificant (OR 1.37,
      95% CI 0.97 to 1.95). CONCLUSIONS: Dermatological manifestations are common in
      ICU patients. Their presence may impact mortality and duration of ventilation and
      hospitalisation.

PMID- 23538395
TI  - Aggravation of pulmonary diffusing capacity in highly trained athletes by 6 weeks
      of low-volume, low-intensity training.
AB  - PURPOSE: Postexercise alveolar-capillary membrane-diffusing capacity (DLco) often
      decreases in highly trained endurance athletes and seems linked to their training
      status. To test the hypothesis that training status influences postexercise DLco,
      13 male and 2 female triathletes (20.2 +/- 4.4 y old, 175.2 +/- 6.7 cm tall;
      weight in a range of 66.6 +/- 7.4 kg to 67.4 +/- 7.8 kg during the 1-y study)
      were randomized into experimental (n = 7) and control (n = 8) groups and
      performed VO(2max) cycle tests and simulated cycle-run successions (CR) of 30 min
      + 20 min after 3 periods in the competitive season. METHODS: Both groups were
      tested before (pre- HTP) and after a 30-wk high-training period (HTP) with high
      training volume, intensity, and frequency. The experimental group was then also
      tested after a 6-wk low-training period (LTP) with low training volume,
      intensity, and frequency, while the control group continued training according to
      the HTP schedule for these 6 wk. Ventilatory data were collected continuously.
      DLco testing was performed before and 30, 60, and 120 min after the CR trials.
      RESULTS: Whatever the period or group, DLco was significantly decreased 30 min
      after CR, with a significantly greater decrease in the experimental group than
      the control group in LTP (-15.7% and -9.3% of DLco, respectively). CONCLUSIONS:
      Six weeks of low training volume and intensity were sufficient to reverse the
      effects of high training volume and intensity on the alveolar-capillary membrane
      after a CR succession in competitive triathletes.

PMID- 23538396
TI  - Formation and characterization of HUF and DUF in solid argon.
AB  - Reactions of laser-ablated U atoms with HF and DF in condensing and solid rare
      gas produce HUF and DUF as the major new products based on close agreement
      between observed and calculated vibrational frequencies and deuterium shifts for
      U-H and U-F stretching modes at 1383 and 544 cm(-1), respectively.

PMID- 23538397
TI  - Synthesis of some novel thieno[3,2-d]pyrimidines as potential cytotoxic small
      molecules against breast cancer.
AB  - A variety of novel thieno[3,2-d]pyrimidines with different decorating functional
      groups were synthesized as a part of a study aiming to enrich the arsenal of
      chemotherapeutic agents for the treatment of cancer. The design of synthetic
      molecules based on DNA-interchelating properties by hydrogen bond formation. The
      reported compounds herein are: 4-aminothienopyrimidine derivatives 4a, b and
      their 4-substituted phenylamino analogues 8a, b; 4-thienopyrimidin-4-ones 5a, b;
      N-alkyl thienopyrimidin-4-ones 6a-g; 4-chlorothienopyrimidines 7a, b and
      thienopyrimidoquinazolinones 9a, b which are the structural mimics of 8a, b. The
      synthesized molecules were evaluated for their in vitro cytotoxic activity
      against human breast cancer cell line (MCF-7). Biological screening revealed
      varying cytotoxic potencies of the tested molecules compared with Doxorubicin as
      a reference drug. The cytotoxicity results from the study suggested that the
      synthesized molecules are potential antitumor agents and compound 4a was the most
      potent with an IC 50 2.04 nm.

PMID- 23538398
TI  - Patients rebuilt: Dr Auguste Rollier's heliotherapeutic portraits, c.1903-1944.
AB  - This article explores and critically contextualises the photographic production
      of heliotherapist Auguste Rollier (1874-1954), specifically the 'patient
      portraits' photographed at his Leysin sanatoria over a substantial period of four
      decades, c.1903-1944. It argues that these photographs, ignored in secondary
      literature, were particularly persuasive in communicating the natural healing
      powers of sunlight and through their international dissemination brought
      Rollier's work professional acclaim and prestige. Always presenting anonymous
      patients, and most often children, the images produced for Rollier's work
      interweave aesthetic and medical interests. Whether through the aesthetics of the
      photograph, of the positioning and appearance of the patient's body, or of the
      language used to describe these, issues of beauty and harmony were significant
      preoccupations for Rollier and the dissemination of his heliotherapeutic
      practice. The article argues that these aesthetic preoccupations drove his work,
      that the patient's progress and final cure, and thus the therapy's efficacy, were
      determined by aesthetic criteria-read through the body itself and its
      photographic representation. This legibility, of the body and its photography,
      was crucial to articulating the sun's perceived natural ability to improve, heal
      and even 'rebuild' individual patients into socially and physically productive
      citizens. As such, the article contends, Rollier privileged image over word,
      conceiving the former as possessing an unequalled 'eloquence' to communicate the
      efficacy and social potential of heliotherapy.

PMID- 23538399
TI  - New public health system is marred by confusion and lack of accountability, say
      MPs.

PMID- 23538400
TI  - Magnetic particle imaging: advancements and perspectives for real-time in vivo
      monitoring and image-guided therapy.
AB  - Magnetic particle imaging (MPI) is an emerging biomedical imaging technology that
      allows the direct quantitative mapping of the spatial distribution of
      superparamagnetic iron oxide nanoparticles. MPI's increased sensitivity and short
      image acquisition times foster the creation of tomographic images with high
      temporal and spatial resolution. The contrast and sensitivity of MPI is
      envisioned to transcend those of other medical imaging modalities presently used,
      such as magnetic resonance imaging (MRI), X-ray scans, ultrasound, computed
      tomography (CT), positron emission tomography (PET) and single photon emission
      computed tomography (SPECT). In this review, we present an overview of the recent
      advances in the rapidly developing field of MPI. We begin with a basic
      introduction of the fundamentals of MPI, followed by some highlights over the
      past decade of the evolution of strategies and approaches used to improve this
      new imaging technique. We also examine the optimization of iron oxide
      nanoparticle tracers used for imaging, underscoring the importance of size
      homogeneity and surface engineering. Finally, we present some future research
      directions for MPI, emphasizing the novel and exciting opportunities that it
      offers as an important tool for real-time in vivo monitoring. All these
      opportunities and capabilities that MPI presents are now seen as potential
      breakthrough innovations in timely disease diagnosis, implant monitoring, and
      image-guided therapeutics.

PMID- 23538401
TI  - Superselective shunt occlusion for the treatment of cavernous sinus dural
      arteriovenous fistulae.
AB  - BACKGROUND: In treating cavernous sinus dural arteriovenous fistulae (CSdAVFs),
      transvenous embolization of the whole affected sinus is usually performed, which
      may result in the disturbance of normal venous drainage or permanent cranial
      nerve palsy. OBJECTIVE: To describe superselective shunt occlusion of CSdAVFs.
      METHODS: Between July 2005 and August 2011, we had 20 consecutive cases of
      CSdAVFs. In 14 cases (70%), we could detect the restricted locus of arteriovenous
      shunts by 3-dimensional rotational angiography and/or superselective
      arteriography. After navigating the microcatheter to the shunt segment,
      consecutive superselective arteriovenography was performed to confirm the
      location of the microcatheter at the proper position. RESULTS: In 12 of 14 cases
      (85.7%) in which the shunt was restricted, coiling only in the small venous pouch
      or compartment, which was just downstream of the shunt point, led to complete
      disappearance of the shunt without obliterating the entire sinus. No recurrence
      or permanent cranial nerve palsy was observed during the follow-up period with a
      mean of 46 months (range, 3-69 months) in 12 cases treated by superselective
      shunt occlusion. CONCLUSION: This technique, which enables complete extirpation
      of shunts by small amounts of coils, is a feasible way to treat CSdAVFs with
      excellent mid- to long-term results. Understanding of the angioarchitecture by 3
      dimensional rotational angiography and consecutive superselective
      arteriovenography was useful. This method should be considered before sinus
      packing or mere obliteration of dangerous venous outlets.

PMID- 23538402
TI  - High phospho-Stathmin(Serine38) expression identifies aggressive endometrial
      cancer and suggests an association with PI3K inhibition.
AB  - PURPOSE: High Stathmin expression has recently been associated with clinical
      progress in endometrial cancers. Stathmin protein activity is modulated by
      phosphorylation, and the Serine38 site is one of four Stathmin phospho-sites. The
      presence and significance of pStathmin(S38) is largely unknown in human cancers,
      and we here examined the associations between this marker and tumor cell
      proliferation, clinicopathologic phenotype, and survival impact in endometrial
      cancer. A relationship with possible treatment targets was explored by integrated
      analysis of transcriptional alterations. EXPERIMENTAL DESIGN: Primary endometrial
      cancers from two independent patient series (n = 518/n = 286) were analyzed.
      Biomarkers were assessed by immunohistochemistry, FISH, flow cytometry, DNA
      oligonucleotide microarray, single-nucleotide polymorphism array, and Sanger
      sequencing, and related to clinicopathologic annotations and follow-up
      information. RESULTS: High pStathmin(S38) level was associated with poor
      prognosis, independent of other features, and correlated to increased tumor cell
      proliferation as well as high Stathmin levels. On the basis of transcriptional
      differences between high/low pStathmin(S38) tumors, phosphoinositide 3-kinase
      (PI3K)/mTOR/HSP90 were suggested as possible targets in pStathmin(S38)-high
      cases. High pStathmin(S38) was associated with several PI3K pathway alterations:
      amplification of the 3q26 region, increased PIK3CA copy number (FISH) and a PI3K
      activation score (all P < 0.05). CONCLUSIONS: High pStathmin(S38) is a novel
      biomarker of increased tumor cell proliferation and impaired prognosis as
      reported here for independent cohorts of endometrial cancer and not previously
      shown in human cancer. Our data support a rationale for further studies exploring
      effects of drugs inhibiting the PI3K signaling pathway in pStathmin(S38)-high
      endometrial cancer, including a potential value of pStathmin(S38) in predicting
      response to PI3K/mTOR/HSP90 inhibitors.

PMID- 23538403
TI  - Concluding remarks on the special issue dedicated to bacterial secretion systems:
      function and structural biology.

PMID- 23538404
TI  - The Sec-dependent pathway.
AB  - The Sec pathway for export of proteins across the cytoplasmic membrane to the
      bacterial periplasm and outer membrane was the first secretion pathway to be
      discovered in bacteria. A combination of bacterial genetics, development of an in
      vitro membrane vesicle system and the concurrent elaboration of the signal
      hypothesis from studies on eukaryotes led to the identification and
      characterization of two pathways leading to protein export through the SecYEG
      cytoplasmic membrane translocon. The Sec pathway is also required for assembly of
      proteins into the cytoplasmic membrane. Since the membrane translocon for Sec
      pathways is conserved across the three domains of life, the history of research
      progress in eukaryotes and bacteria was facilitated by the close interaction
      between those studying both classes of organisms.

PMID- 23538405
TI  - Type II secretion: the substrates that won't go away.
AB  - Type II secretion systems (T2SSs) generally release their substrates into the
      culture medium. A few T2SS substrates remain anchored to or bound at the surface
      of the bacteria after secretion. Since they handle already folded proteins, T2SSs
      are the best way for bacteria to target, at their surface, proteins containing a
      cofactor, proteins that have to be folded in the cytoplasm or in the periplasm,
      or multimeric proteins. However, how a T2SS deals with membrane-anchored proteins
      is not yet understood. While this type of protein has until now been overlooked,
      new proteomic approaches will facilitate its identification.

PMID- 23538406
TI  - Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.
AB  - BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human
      prion cases and are a frequent cause of early onset dementia. The purpose of this
      study was to define the distribution of changes in cerebral volumetric and
      microstructural parenchymal tissues in a specific inherited human prion disease
      mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS:
      VBM and VBA of cerebral MTR and MD were performed in 16 healthy control
      participants and 9 patients with the 6-OPRI mutation. An analysis of covariance
      consisting of diagnostic grouping with age and total intracranial volume as
      covariates was performed. RESULTS: On VBM, there was a significant reduction in
      gray matter volume in patients compared with control participants in the basal
      ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR
      reduction and MD increases were more anatomically extensive than volume
      differences on VBM in the same cortical areas, but MTR and MD changes were not
      seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in
      brain areas associated with motor and cognitive functions known to be impaired in
      patients with the 6-OPRI mutation. There were some differences in the anatomic
      distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect
      regional variations in the type and degree of the respective pathophysiologic
      substrates. Combined analysis of complementary multiparameter MR imaging data
      furthers our understanding of prion disease pathophysiology.

PMID- 23538408
TI  - New applications of nanotechnology for neuroimaging.
AB  - SUMMARY: Advances in nanotechnology have the potential to dramatically enhance
      the detection of neurologic diseases with targeted contrast agents and to
      facilitate the delivery of focused therapies to the central nervous system. We
      present the physicochemical rationale for their use, applications in animal
      models, and ongoing clinical trials using these approaches. We highlight advances
      in the use of nanoparticles applied to brain tumor imaging, tumor angiogenesis,
      neurodegeneration, grafted stem cells, and neuroprogenitor cells.

PMID- 23538407
TI  - Histopathologic evaluation of arterial wall response to 5 neurovascular
      mechanical thrombectomy devices in a swine model.
AB  - BACKGROUND AND PURPOSE: Five commercial devices are available for mechanical
      thrombectomy in acute ischemic stroke. This study evaluated and compared the
      resultant arterial damage from these devices. MATERIALS AND METHODS: Wall damage
      after 4 wall-contact devices (the Merci retriever, Catch thromboembolectomy
      system, and Solitaire FR revascularization devices of 4 and 6 mm) and 1
      aspiration device (the Penumbra System) was evaluated in the superficial femoral
      arteries of 20 male swine. Each device was tested with and without intraluminal
      clot. Twenty control vessels were not subjected to any intervention. Acute
      histopathologic changes were evaluated. RESULTS: In the device samples,
      endothelial denudation (72.8 +/- 29.4% versus 0.9 +/- 1.9%, P < .0001), medial
      layer edema (52 +/- 35.9% versus 18.1 +/- 27.8%, P = .004), and mural thrombus
      (5.3 +/- 14.2% versus 0%, P = .05) were found to a greater extent compared with
      the control samples. The aspiration device provoked more intimal layer (100 +/-
      79.1% versus 58.8 +/- 48.9%, P = .27) and medial layer (75 +/- 35.4% versus 46.3
      +/- 34.8%, P = .13) edema than the wall-contact devices. CONCLUSIONS: All devices
      caused vascular injuries extending into the medial layer. The aspiration device
      was associated with more intimal and medial layer edema, compared with the wall
      contact devices except for the Catch thromboembolectomy system.

PMID- 23538409
TI  - Double stent-assisted coil embolization treatment for bifurcation aneurysms:
      immediate treatment results and long-term angiographic outcome.
AB  - BACKGROUND AND PURPOSE: The goal of endovascular treatment of cerebral
      bifurcation aneurysms is to achieve safe coiling of the sac along with preserving
      patency of the diverging branches. Our purpose was evaluate procedural safety and
      efficacy as well as the long-term durability of endovascular treatment of
      bifurcation aneurysms with double stent-assisted coiling. MATERIALS AND METHODS:
      One hundred ninety-one consecutive patients with bifurcation aneurysms were
      included in this series. Technical failure occurred in 3 aneurysms (1.5%); 188
      patients with 193 aneurysms treated with double stent-assisted coiling were
      retrospectively evaluated; 113 aneurysms were located at middle cerebral artery
      bifurcation, 42 at the anterior communicating artery, 22 at the basilar artery
      bifurcation, and the remaining 16 at the internal carotid artery bifurcation; 132
      were small (<10 mm), 56 were large (10-25 mm), and 5 were giant (>25 mm).
      RESULTS: The technical success rate of double-stent application was 98.5% (193
      aneurysms). In total, there were 5 procedural complications with an associated
      rate of 2.7%, one of which led to death (0.5%). Delayed ischemic stroke occurred
      in 2 patients (1.1%). Overall, permanent morbidity occurred in 2 patients, with
      associated rate of 1.1%. Follow-up was obtained in 186 aneurysms (96.4%), and
      recanalization occurred in 4 aneurysms (2.2%). In subgroup analysis, the
      recanalization rate was 3.8% for large aneurysms and 40% for giant aneurysms. No
      recanalization occurred in small aneurysms. CONCLUSIONS: Dual stent-assisted
      coiling of cerebral aneurysms is a feasible and safe procedure. It may offer a
      curative solution with long-term durability for treatment of wide-neck small and
      large aneurysms.

PMID- 23538410
TI  - Comparison of 10 TTP and Tmax estimation techniques for MR perfusion-diffusion
      mismatch quantification in acute stroke.
AB  - BACKGROUND AND PURPOSE: The mismatch between lesions identified in perfusion- and
      diffusion-weighted MR imaging is typically used to identify tissue at risk of
      infarction in acute stroke. The purpose of this study was to analyze the
      variability of mismatch volumes resulting from different time-to-peak or time-to
      maximum estimation techniques used for hypoperfused tissue definition. MATERIALS
      AND METHODS: Data of 50 patients with middle cerebral artery stroke and
      intracranial vessel occlusion imaged within 6 hours of symptom onset were
      analyzed. Therefore, 10 different TTP/Tmax techniques and delay thresholds
      between +2 and +12 seconds were used for calculation of perfusion lesions.
      Diffusion lesions were semiautomatically segmented and used for mismatch
      quantification after registration. RESULTS: Mean volumetric differences up to 40
      and 100 mL in individual patients were found between the mismatch volumes
      calculated by the 10 TTP/Tmax estimation techniques for typically used delay
      thresholds. The application of typical criteria for the identification of
      patients with a clinically relevant mismatch volume resulted in different
      mismatch classifications in <=24% of all cases, depending on the TTP/Tmax
      estimation method used. CONCLUSIONS: High variations of tissue-at-risk volumes
      have to be expected when using different TTP/Tmax estimation techniques. An
      adaption of different techniques by using correction formulas may enable more
      comparable study results until a standard has been established by agreement.

PMID- 23538411
TI  - Brain mapping project: clinical aspects and role of neuroradiology.
AB  - As experts in the realm of applying brain imaging technology for meaningful
      information on an individual patient's medical care, neuroradiologists can
      provide a physiologic, pathophysiologic, and clinical context for the advances
      achieved from brain-mapping. Precise identification of the abnormalities involved
      in brain conditions resulting from a multidisciplinary effort including
      neuroradiology will help to further define the nature of the pathology, evaluate
      the results of therapy, and improve health care.

PMID- 23538412
TI  - Genetics of Alzheimer disease.
AB  - Alzheimer disease prevails as a major cause of disability in the elderly
      population and ranks as the most common form of dementia that affects 1 of 8
      individuals older than 65 years of age. Most AD cases are late in onset and are
      probably influenced by both genetic and environmental factors. Apart from age,
      the risk factors include family history; brain injury, both traumatic and
      vascular; and metabolic diseases, such as diabetes, hypercholesterolemia, and
      obesity. Based on twin studies, inheritance plays a role in approximately 80% of
      cases (familial and sporadic).

PMID- 23538413
TI  - Imaging of the 6-OPRI mutation prion disease: an entity distinct from typical
      Creutzfeldt-Jakob disease?

PMID- 23538414
TI  - Traumatic brain stem injury: evaluation by MRI.

PMID- 23538415
TI  - Dynamic contrast-enhanced MR: importance of reaching the washout phase.

PMID- 23538416
TI  - High-pass-filtered phase image: left- versus right-handed MR imaging systems.

PMID- 23538417
TI  - ProNGF?NGF imbalance triggers learning and memory deficits, neurodegeneration and
      spontaneous epileptic-like discharges in transgenic mice.
AB  - ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant
      form of NGF in the brain. ProNGF and mature NGF differ significantly in their
      receptor interaction properties and in their bioactivity. ProNGF increases
      markedly in the cortex of Alzheimer's disease (AD) brains and proNGF?NGF
      imbalance has been postulated to play a role in neurodegeneration. However, a
      direct proof for a causal link between increased proNGF and AD neurodegeneration
      is lacking. In order to evaluate the consequences of increased levels of proNGF
      in the postnatal brain, transgenic mice expressing a furin cleavage-resistant
      form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter,
      were derived and characterized. Different transgenic lines displayed a phenotypic
      gradient of neurodegenerative severity features. We focused the analysis on the
      two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory
      impairments in behavioral tests, cholinergic deficit and increased Abeta-peptide
      immunoreactivity. In addition, TgproNGF#3 mice developed Abeta oligomer
      immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also
      display electrophysiological alterations related to spontaneous epileptic-like
      events. The results provide direct evidence that alterations in the proNGF/NGF
      balance in the adult brain can be an upstream driver of neurodegeneration,
      contributing to a circular loop linking alterations of proNGF/NGF equilibrium to
      excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP)
      dysmetabolism. 

PMID- 23538418
TI  - Two hot spot mutant p53 mouse models display differential gain of function in
      tumorigenesis.
AB  - Mutant p53 proteins not only lose their tumor-suppressor function but some
      acquire oncogenic gain of function (GOF). The published mutp53 knock-in (KI)
      alleles (R172H, R270H, R248W) manifest GOF by broader tumor spectrum and more
      metastasis compared with the p53-null allele, but do not shorten survival.
      However, whether GOF also occurs with other mutations and whether they are all
      biologically equal is unknown. To answer this, we created novel humanized mutp53
      KI mice harboring the hot spot alleles R248Q and G245S. Intriguingly, their
      impact was very different. Compared with p53-null mice, R248Q/- mice had
      accelerated onset of all tumor types and shorter survival, thus unprecedented
      strong GOF. In contrast, G245S/- mice were similar to null mice in tumor latency
      and survival. This was associated with a twofold higher T-lymphoma proliferation
      in R248Q/- mice compared with G245S/- and null mice. Moreover, R248Q/-
      hematopoietic and mesenchymal stem cells were expanded relative to G245S/- and
      null mice, the first indication that GOF also acts by perturbing pretumorous
      progenitor pools. Importantly, these models closely mirror Li-Fraumeni patients
      who show higher tumor numbers, accelerated onset and shorter tumor-free survival
      by 10.5 years when harboring codon R248Q mutations as compared with Li-Fraumeni
      patients with codon G245S mutations or p53 deletions/loss. Conversely, both KI
      alleles caused a modest broadening of tumor spectrum with enhanced Akt signaling
      compared with null mice. These models are the first in vivo proof for
      differential oncogenic strength among p53 GOF alleles, with genotype-phenotype
      correlations borne out in humans.

PMID- 23538421
TI  - Ethical publication providing social benefit: challenges of editors and the ABEC
      Brasil.

PMID- 23538419
TI  - Analysis of the oligomeric state and transactivation potential of TAp73alpha.
AB  - The proteins p73 and p63 are members of the p53 protein family and are involved
      in important developmental processes. Their high sequence identity with the tumor
      suppressor p53 has suggested that they act as tumor suppressors as well. While
      p63 has a crucial role in the maintenance of epithelial stem cells and in the
      quality control of oocytes without a clear role as a tumor suppressor, p73's
      tumor suppressor activity is well documented. In a recent study we have shown
      that the transcriptional activity of TAp63alpha, the isoform responsible for the
      quality control in oocytes, is regulated by its oligomeric state. The protein
      forms an inactive, dimeric and compact conformation in resting oocytes, while the
      detection of DNA damage leads to the formation of an active, tetrameric and open
      conformation. p73 shows a high sequence identity to p63, including those domains
      that are crucial in stabilizing its inactive state, thus suggesting that p73's
      activity might be regulated by its oligomeric state as well. Here, we have
      investigated the oligomeric state of TAp73alpha by size exclusion chromatography
      and detailed domain interaction mapping, and show that in contrast to p63,
      TAp73alpha is a constitutive open tetramer. However, its transactivation
      potential depends on the cellular background and the promoter context. These
      results imply that the regulation of p73's transcriptional activity might be more
      closely related to p53 than to p63. 

PMID- 23538422
TI  - Caries experience in young children with congenital heart disease in a developing
      country.
AB  - Oral care is frequently suboptimal in children from developing countries,
      especially those suffering from severe systemic diseases. The aim of the present
      study was to analyze the oral epidemiological profile of 3-to-5-year-old children
      with congenital heart disease. Dental and medical records of children evaluated
      at the Dental Service of the National Institute of Cardiology, Rio de Janeiro,
      Brazil, were reviewed. Caries experience was reported using the dmft index.
      Negative behavior towards dental management was recorded. The sample consisted of
      144 children aged 4.41 +/- 0.95 years. The mean dmft value was 5.4 +/- 4.9, and
      80.5% had at least one caries lesion. Dmft index was greater in the presence of
      cyanotic cardiac disease and in children with negative behavior. An increase in
      the "missing" component of the dmft index was also found in children using
      medicine on a daily basis. A higher caries experience was associated with
      children whose fathers had only an elementary education. In conclusion, children
      with congenital heart disease had high levels of caries experience at a young
      age. Cyanosis, negative behavior, daily use of medicine, one-parent family and
      the educational level of fathers seem to influence caries experience in children
      with congenital cardiac disease.

PMID- 23538423
TI  - New trends in dentistry: plant extracts against Enterococcus faecalis. The
      efficacy compared to chlorhexidine.
AB  - Enterococcus faecalis is an important pathogen associated with endodontic
      diseases, and its elimination and control are of paramount importance, as it
      represents one of the major causes of failure in the treatment of endodontic
      disease. Twenty-five plant extracts obtained from Brazilian forests were found to
      be effective against planktonic E. faecalis and were subjected to two traditional
      antibacterial assays, the microdilution broth assay (MDBA) and the disk diffusion
      assay (DDA), using chlorhexidine (CHX) as a control. Seven out of 25 extracts
      showed significant antibacterial activity and were tested in a biofilm assay, and
      three of these extracts were subjected to chemical fractionation. Residues were
      tested for their antibacterial activity, and the first chemical findings were
      described based on thin layer chromatography (TLC). Extracts obtained from
      Ipomoea alba, Symphonia globulifera and Moronobea coccinea showed significant
      bactericidal activity in the MDBA. The same I. alba and S. globulifera extracts,
      as well as the extract obtained from Connarus ruber var. ruber, showed
      significant activity in the DDA. RH2O obtained from Psidium densicomum and
      Stryphnodendron pulcherrimum showed better antibacterial activity compared to the
      respective crude extracts and CHX. TLC analysis showed that phenolic compounds
      and triterpenes represent the first findings of chemical groups that may occur in
      all species. The results of the present study include the discovery of six active
      extracts against planktonic E. faecalis and support further testing via assays
      involving biofilm formation, as well as the determination of the compounds'
      chemical profiles, as their activity was significantly better than that observed
      for CHX.

PMID- 23538424
TI  - Concordance between cytopathology and incisional biopsy in the diagnosis of oral
      squamous cell carcinoma.
AB  - Oral cytopathology is a simple, non-invasive technique that could be used for
      early detection of oral premalignant and malignant lesions, but the effectiveness
      of this diagnostic approach remains controversial. The aim of this study was to
      evaluate the sensitivity, specificity, positive and negative predictive values,
      and accuracy of cytopathology for diagnosing oral squamous cell carcinoma (OSCC)
      and the diagnostic concordance between cytopathological and histopathological
      diagnoses. The study enrolled 172 patients at outpatient clinics who presented
      with oral lesions suspicious of malignancy. All patients underwent oral
      cytological scrapes followed by an incisional biopsy. Of 148 cases that were
      histopathologically diagnosed with OSCC, the cytopathological method diagnosed
      123 positive cases and resulted in a suspicion of OSCC in 16 patients. Based on
      these data, the sensitivity was 83.1%, the specificity was 100.0%, the positive
      predictive value was 100.0%, the negative predictive value was 49.0%, and the
      accuracy was 85.5%. The diagnostic concordance between histopathological and
      cytopathological examinations was 83.1% for OSCC and 85.7% for non-neoplastic
      lesions. The results indicate that cytopathological diagnosis had good
      concordance with histopathological diagnosis and showed high sensitivity,
      specificity, positive predictive value, and accuracy. We conclude that the
      sensitivity of oral cytopathology is sufficient to justify its use as a
      diagnostic screening test and to confirm the malignant nature of epithelial
      cells, mainly for the classification of OSCC. Therefore, cytopathology may be a
      reliable method for referring patients who require diagnosis of suspected oral
      cancer for starting treatment.

PMID- 23538425
TI  - Influence of microhybrid resin and etching times on bleached enamel for the
      bonding of ceramic brackets.
AB  - The aim of this study was to evaluate the shear bond strength (SBS) of
      polycrystalline ceramic brackets (PCB) bonded after bleaching treatment using
      different composite resins and enamel etching times. A total of 144 bovine
      incisors were randomly divided into two study groups (n = 72, each) as follows:
      G1, enamel bleached with 35% hydrogen peroxide, and G2 (control group), enamel
      unbleached. After the bleaching treatment, the samples were stored in artificial
      saliva for 14 days. These groups were further divided into two subgroups (n = 36,
      each) as follows: GA, brackets bonded with Transbond XT (3M) and GB, brackets
      bonded with Filtek Z250 (3M). For each resin used, three different etching times
      with 37% phosphoric acid (15, 30 and 60 seconds) were tested. SBS tests were
      performed using a universal testing machine (EMIC), and the adhesive remnant
      index (ARI) score was verified. Significant differences among the three
      experimental conditions and interactions between the groups were observed. The
      type of composite resin accounted for 24% of the influence on the bond strength,
      whereas the etching time and bleaching treatment accounted for 14.5% and 10% of
      the influence on bond strength, respectively. The ARI revealed that the most
      common area of adhesion failure was at the composite resin-bracket interface. The
      type of composite resin, etching time and external bleaching significantly
      influenced the SBS of PCB on enamel, even after 14 days of saliva storage.

PMID- 23538426
TI  - An investigation of the presence of specific anaerobic species in necrotic
      primary teeth.
AB  - Different microbial identification methods have shown that the microbial
      community profiles in endodontic infections are diverse and assorted. The aim of
      this study was to evaluate the frequency of selected endodontic pathogens in the
      pulp chambers (PCs) and root canals (RCs) of infected primary teeth using PCR
      methods. Paired PC and RC samples were collected from 15 subjects and analyzed by
      PCR for the presence of Filifactor alocis, Fusobacterium nucleatum, Parvimonas
      micra, Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella
      intermedia, Prevotella nigrescens, Prevotella tannerae, Tanerella forsythia,
      Treponema denticola, and Treponema socranskii. The frequency of each species was
      determined in the PC and RC of each case. The species most frequently detected in
      PCs were P. nigrescens (86.7%), P. gingivalis (73.3%), and F. alocis (73.3%). Of
      the PC samples, 13.3% contained P. micra and T. denticola, and 6.7% contained T.
      forsythia. The species most frequently detected in RCs were P. gingivalis (100%)
      and P. nigrescens (93.3%). P. tannerae, P. micra, and T. denticola were found in
      40% of the RC samples; T. forsythia was found in 26.7% of the RC samples. The
      "red complex", which comprises P. gingivalis, T. denticola, and T. forsythia, was
      not found in the PC of any tooth but was found in 30% of the RC samples. The
      detection of P. nigrescens in the PC was statistically associated with the
      presence of P. nigrescens in the RC (p = 0.04). The results suggest high
      heterogeneity among the samples, even among those from the same subject.

PMID- 23538427
TI  - Anxiety/depression and orofacial myofacial disorders as factors associated with
      TMD in children.
AB  - The purpose of this study was to evaluate factors associated with
      temporomandibular disorder (TMD) in children. TMD clinical signs were evaluated
      using the Research Diagnostic Criteria for TMD (RDC/TMD; axis I), and subjective
      symptoms were evaluated using a structured questionnaire. Eighty-two children
      were selected, 40 with TMD (19 boys and 21 girls, mean age 9.84 +/- 1.53 and 9.71
      +/- 1.30 years, respectively) and 42 without TMD (21 boys and 21 girls, mean age
      10.27 +/- 1.63 and 9.9 +/- 1.37 years, respectively). Intra- and extra-oral
      examinations were carried out to determine the myofunctional characteristics of
      the masticatory system. The Hospital Anxiety and Depression Scale (HADS) was used
      to assess anxiety and depression. Data were analyzed using descriptive statistics
      and bivariate analysis followed by multiple logistic regression (alpha = 0.05).
      In bivariate analysis, the variables of open lips, anxiety, and depression had a
      p value < 0.15 and were entered into the multivariate logistic regression model.
      The most significant predictor factors were the presence of open lips (odds ratio
      = 5.42, p = 0.034) and anxiety (odds ratio = 18.59, p < 0.001). Thus, anxiety
      levels and open lips were associated with TMD in children. Owing to the cross
      sectional design of the present study, the associations observed may have a
      bidirectional relationship.

PMID- 23538428
TI  - Child abuse: validation of a questionnaire translated into Brazilian Portuguese.
AB  - This study sought to validate the Portuguese translation of a questionnaire on
      maltreatment of children and adolescents, developed by Russell et al. and to test
      its psychometric properties for use in Brazil. The original questionnaire was
      translated into Portuguese using a standardized forward-backward linguistic
      translation method. Both face and content validity were tested in a small pilot
      study (n = 8). In the main study, a convenience sample of 80 graduate dentistry
      students with different specialties, from Curitiba, PR, Brazil, were invited to
      complete the final Brazilian version of the questionnaire. Discriminant validity
      was assessed by comparing the results obtained from the questionnaire for
      different specialties (pediatric dentistry, for example). The respondents
      completed the questionnaire again after 4 weeks to evaluate test-retest
      reliability. The comparison of test versus retest questionnaire answers showed
      good agreement (kappa > 0.53, intraclass correlation > 0.84) for most questions.
      In regard to discriminant validity, a statistically significant difference was
      observed only in the experience and interest domains, in which pediatric dentists
      showed more experience with and interest in child abuse compared with dentists of
      other specialties (Mann-Whitney test, p < 0.05). The Brazilian version of the
      questionnaire was valid and reliable for assessing knowledge regarding child
      abuse by Portuguese-speaking dentists.

PMID- 23538429
TI  - Evaluation of roughness and micromorphology of epoxy paint on cobalt-chromium
      alloy before and after thermal cycling.
AB  - It has been suggested that the epoxy paint used to coat metal substrates in
      industrial electrostatic painting applications could also be used to mask metal
      clasps in removable dental prostheses (RDP). The purpose of this study was to
      evaluate both the influence of thermal cycling and the in vitro roughness of a
      surface after application of epoxy paint, as well as to assess the
      micromorphology of a cobalt-chromium (CoCr) based metal structure. Sixty test
      specimens were fabricated from a CoCr alloy. The specimens were separated into
      three groups (n = 20) according to surface treatment: Group 1 (Pol) - polished
      with abrasive stone and rubbers; Group 2 (Pol+Epo) - polished and coated with
      epoxy paint; Group 3 (Epo) - air-abraded with aluminum oxide particles and coated
      with epoxy paint. The surface roughness was evaluated before and after 1000
      thermal cycles (5 degrees C and 50 degrees C). The surface micromorphology was
      verified by scanning electron microscopy (SEM). The two-way repeated measures
      ANOVA showed significant differences among surface treatments (p < 0.0001), but
      no difference was found before and after thermal cycling (p = 0.6638). The CoCr
      based metal alloy surfaces treated with epoxy paint (Groups 2 and 3) were rougher
      than the surfaces that were only polished (Group 1). Thermal cycling did not
      influence surface roughness, or lead to chipping or detachment of the epoxy
      paint.

PMID- 23538430
TI  - Is there justification for prophylactic extraction of third molars? A systematic
      review.
AB  - The present systematic review was performed to investigate if there is evidence
      justifying the prophylactic extraction of third molars, one of the most frequent
      procedures in oral surgery. A series of searches was carried out for randomized,
      clinical trials and systematic reviews in seven databases (MEDLINE, BBO, LILACS,
      Web of Science, EMBASE, BIREME and Cochrane Library), with no restrictions
      regarding year or language. A supplemental manual search of the references of
      retrieved articles was also performed. The search strategy resulted in 260
      papers. Both the data extracted and the quality of each paper were evaluated
      independently by two reviewers. After selection based on the preestablished
      eligibility criteria, four papers qualified for the final analysis. A medium
      degree of quality and methodological consistency was found in three studies, and
      low quality was found in one study. No studies showed a high degree of
      consistency. The most significant flaw was an inadequate sample size. The results
      of the present review indicate a lack of scientific evidence to justify the
      indication of the prophylactic extraction of third molars.

PMID- 23538431
TI  - Increased lean mass with reduced fat mass in an elite female cyclist returning to
      competition: case study.
AB  - Body composition in a female road cyclist was measured using dual-energy X-ray
      absorptiometry (5 occasions) and anthropometry (10 occasions) at the start of the
      season (Dec to Mar), during a period of chronic fatigue associated with poor
      weight management (Jun to Aug), and in the following months of recovery and
      retraining (Aug to Nov). Dietary manipulation involved a modest reduction in
      energy availability to 30-40 kcal . kg fat-free mass(-1) . d(-1) and an increased
      intake of high-quality protein, particularly after training (20 g). Through the
      retraining period, total body mass decreased (-2.82 kg), lean mass increased
      (+0.88 kg), and fat mass decreased (-3.47 kg). Hemoglobin mass increased by 58.7
      g (8.4%). Maximal aerobic- and anaerobic-power outputs were returned to within 2%
      of preseason values. The presented case shows that through a subtle energy
      restriction associated with increased protein intake and sufficient energy intake
      during training, fat mass can be reduced with simultaneous increases in lean
      mass, performance gains, and improved health.

PMID- 23538432
TI  - Generation of single-domain antibody multimers with three different self
      associating peptides.
AB  - Conventional Y-shaped antibodies have been widely used in research, diagnostics
      and therapeutics. Their large size result in disadvantages in certain
      applications, which makes production difficult. Different parts of an antibody
      have been used to replace the whole antibody to make it smaller. Single-domain
      antibodies (sdAbs) derived from the camelid heavy chain antibodies are among the
      smallest antibody fragments engineered for various applications. To improve the
      affinity of these single- sdAbs for correspondent antigens and provide suitable
      size of reagents for various applications, we fused an anti-epidermal growth
      factor receptor sdAb EG2 to self-associating peptides, RHCC derived from a right
      handed coiled-coil peptide of an archaebacterium, COMPcc from human cartilage
      oligomeric matrix protein and C4bpalpha derived from human plasma C4-binding
      protein alpha-chain, respectively, to make multimeric antibodies. The multimeric
      antibodies were expressed as soluble cytoplasmic proteins to spontaneously form
      tetramers, pentamers or heptamers and were purified by affinity chromatography.
      The avidity of multimeric forms of sdAbs compared with that of the monomeric form
      of sdAbs was increased without altering binding specificity.

PMID- 23538433
TI  - C-reactive protein and complement components in patients with pathological
      myopia.
AB  - PURPOSE: To investigate the association between pathological myopia (PM) and
      immunological/inflammatory markers and to identify the possible risk factors for
      the formation of myopic choroidal neovascularization (mCNV). METHODS: One hundred
      fourteen unrelated subjects were recruited: 63 PM patients (PM group) with
      spherical equivalent of at least -8.00 diopters (range, -8.00 to -25.00) and
      axial length exceeding 26.5 mm, accompanied by characteristic pathologic changes,
      and 51 emmetropic age- and sex-matched individuals (control group) with spherical
      equivalent within +/-1.0 diopter in both eyes. In the PM group, patients were
      assigned to two subgroups, mCNV group and no CNV group, according to the results
      of fluorescein angiography. Serum high-sensitivity C-reactive protein (hs-CRP)
      and complement profile (C3, C4, and CH50) were assayed. Statistical analysis was
      performed between the two groups. Binary logistic regression analysis was used to
      analyze the relative risk factors that were associated with the development of
      mCNV in the PM group patients. RESULTS: The range of axial length was 26.50 to
      37.08 mm in the PM group and 22.32 to 24.56 mm in the control group. There were
      24 patients in the mCNV group and 39 patients in the no CNV group. The PM group
      patients had significantly higher serum hs-CRP (p = 0.033), C3 (p = 0.004), and
      CH50 (p < 0.001) compared with the control group patients. There were no
      significant differences between the two groups for C4 level (p = 0.071). Binary
      logistic regression analysis, which included hs-CRP, C3, C4, CH50, age, and sex
      as covariates, showed that C3 (p = 0.03) and age (p = 0.01) were risk factors for
      mCNV, whereas serum hs-CRP, C4, CH50, and sex were not statistically significant
      predictors of mCNV in the PM group patients (p > 0.05). CONCLUSIONS: Our data
      support the hypothesis that immunological/inflammatory markers, namely hs-CRP,
      C3, and CH50 may play an important role in the development of PM, and that C3
      level may be a predictive risk factor for mCNV formation.

PMID- 23538434
TI  - Nearwork-induced transient myopia and parental refractive error.
AB  - PURPOSE: To investigate the relationship between parental refractive error and
      the nearwork-induced transient myopia (NITM) characteristics of their children.
      METHODS: Three hundred sixty children (173 boys and 187 girls) aged 6 to 17 years
      were tested. Initial NITM and its decay time (DT) were assessed objectively (WAM
      5500, Grand-Seiko) immediately after binocularly viewing and performing a
      sustained near task (5 diopters [D]) for 5 minutes, incorporating a cognitive
      demand with full distance refractive correction in place. The NITM was classified
      into three categories: low (< 0.15 D), moderate (0.15 to 0.30 D), or high (>=0.30
      D), whereas its decay was classified into two categories, namely, complete or
      incomplete. In addition, the children were divided into three groups based on the
      number of myopic parents (none, one, or two) and into four groups based on the
      level of parental myopia (no, low, moderate, or high). RESULTS: Neither paternal
      nor maternal refractive error was associated with either their children's initial
      NITM magnitude or its DT in the myopic, emmetropic, or hyperopic groups or the
      combined group. No significant differences (p > 0.05) in the NITM magnitude, DT,
      or decay time constant were found as related to the number of myopic parents or
      level of parental myopia. Multiple odds ratio for incomplete decay of NITM did
      not change significantly (p > 0.05) with either an increase in number of myopic
      parents or level of parental myopia. CONCLUSIONS: There was no association
      between parental refractive error and their children's NITM characteristics. This
      suggests a primary environmental basis for the NITM characteristics in the
      children.

PMID- 23538435
TI  - Effect of lens and solution choice on the comfort of contact lens wearers.
AB  - PURPOSE: To determine if the ocular comfort of symptomatic contact lens (CL)
      wearers can be substantially influenced by choosing a better or worse performing
      CL-lens care product (LCP) combination. METHODS: Twenty-four symptomatic and 13
      nonsymptomatic CL wearers were enrolled into a prospective, crossover, randomized
      clinical trial. Two CL-LCP combinations were chosen from studies previously
      conducted at the Brien Holden Vision Institute that were found to provide the
      best (galyfilcon A/polyhexanide, combination 1) and worst performance (balafilcon
      A/polyquaternium-1 and myristamidopropyl dimethylamine + TearGlyde, combination
      2) in terms of end-of-day comfort. Subjects were not informed whether they were
      categorized as symptomatic or nonsymptomatic nor were they aware of the rankings
      of each CL-LCP combination. Subjects were randomly allocated to one of the CL-LCP
      combinations for 8 days on a daily wear basis. Contact lens fitting was assessed
      after insertion from the packaging solution. Take-home questionnaires assessing
      ocular comfort and dryness (1 to 10 numeric rating scale) were completed on
      insertion and after 2 and 8 hours of wear on days 2, 4, and 6. Ocular symptoms
      were assessed on days 2, 4, and 6 after 8 hours of wear. A 48-hour washout period
      during which CLs were not worn was applied, with the procedure repeated using the
      second combination. RESULTS: In symptomatic subjects, combination 1 was rated
      significantly better than combination 2 after 8 hours of wear for ocular comfort
      (7.7 +/- 1.3 vs. 7.1 +/- 1.5, p = 0.01) and ocular dryness (7.5 +/- 1.6 vs. 7.0
      +/- 1.6, p = 0.045), with less frequent symptoms of ocular dryness (p < 0.01) and
      lens awareness (p < 0.01) reported. No significant differences were found in
      nonsymptomatic subjects. CONCLUSIONS: Ocular comfort and symptoms in symptomatic
      CL wearers can be perceptibly improved by switching to an alternative CL-LCP
      combination. This finding provides justification for the efforts of both eye care
      practitioners and researchers to improve the comfort of CL wearers.

PMID- 23538436
TI  - Corneal versus ocular aberrations after overnight orthokeratology.
AB  - PURPOSE: To investigate relationships between changes to corneal and ocular
      aberrations induced by orthokeratology (OK) and their influence on visual
      function. METHODS: Eighteen subjects (aged 20 to 23 years) were fitted with OK
      lenses (BE Enterprises Pty Ltd, Australia), manufactured in Boston XO material
      (Bausch & Lomb Boston, Wilmington, MA), and worn overnight for seven nights.
      Corneal and ocular aberrations were simultaneously captured (Discovery,
      Innovative Visual Systems, Elmhurst, IL), and contrast sensitivity function was
      measured on days 1 and 7, within 2 and 8 hours after lens removal on waking. Data
      from the eye achieving the higher myopic correction were analyzed for changes
      over time. RESULTS: There was a significant refractive effect at all visits.
      Orthokeratology induced an increase in corneal and ocular root mean square higher
      order aberrations (HOAs) and a positive shift in spherical aberration (SA) on day
      1, with further increases by day 7. Increases in root mean square coma became
      significant by day 7. Changes to corneal and ocular SA were similar on day 1;
      however, by day 7, there was a greater increase in corneal than ocular SA,
      indicating a change in internal SA. Orthokeratology led to an overall decrease in
      contrast sensitivity function, which was isolated to spatial frequency changes on
      day 1 at 1 cycle per degree and on day 7 at 1 and 8 cycles per degree.
      CONCLUSIONS: A greater positive shift in corneal compared with ocular SA on day 7
      suggests a negative shift in internal SA, which would be consistent with an
      increased accommodative response. Lack of any difference on day 1 indicates that
      this may be an ocular adaptation response toward neutralizing induced positive
      SA, rather than a direct effect of SA changes on the accommodation mechanism.

PMID- 23538437
TI  - Blink rate, incomplete blinks and computer vision syndrome.
AB  - PURPOSE: Computer vision syndrome (CVS), a highly prevalent condition, is
      frequently associated with dry eye disorders. Furthermore, a reduced blink rate
      has been observed during computer use. The present study examined whether post
      task ocular and visual symptoms are associated with either a decreased blink rate
      or a higher prevalence of incomplete blinks. An additional trial tested whether
      increasing the blink rate would reduce CVS symptoms. METHODS: Subjects (N = 21)
      were required to perform a continuous 15-minute reading task on a desktop
      computer at a viewing distance of 50 cm. Subjects were videotaped during the task
      to determine their blink rate and amplitude. Immediately after the task, subjects
      completed a questionnaire regarding ocular symptoms experienced during the trial.
      In a second session, the blink rate was increased by means of an audible tone
      that sounded every 4 seconds, with subjects being instructed to blink on hearing
      the tone. RESULTS: The mean blink rate during the task without the audible tone
      was 11.6 blinks per minute (SD, 7.84). The percentage of blinks deemed incomplete
      for each subject ranged from 0.9 to 56.5%, with a mean of 16.1% (SD, 15.7). A
      significant positive correlation was observed between the total symptom score and
      the percentage of incomplete blinks during the task (p = 0.002). Furthermore, a
      significant negative correlation was noted between the blink score and symptoms
      (p = 0.035). Increasing the mean blink rate to 23.5 blinks per minute by means of
      the audible tone did not produce a significant change in the symptom score.
      CONCLUSIONS: Whereas CVS symptoms are associated with a reduced blink rate, the
      completeness of the blink may be equally significant. Because instructing a
      patient to increase his or her blink rate may be ineffective or impractical,
      actions to achieve complete corneal coverage during blinking may be more helpful
      in alleviating symptoms during computer operation.

PMID- 23538438
TI  - Strategies and opportunities for drug development in heart failure.

PMID- 23538439
TI  - Cardamonin suppresses the proliferation of colon cancer cells by promoting beta
      catenin degradation.
AB  - Aberrant accumulation of intracellular beta-catenin and subsequent activation of
      beta-catenin response transcription (CRT) in intestinal epithelial cells is a
      frequent early event during the development of colon cancer. Here we show that
      cardamonin, a chalcone isolated from Aplinia katsumadai Hayata, inhibited CRT in
      SW480 colon cancer cells that carry inactivating mutation in the adenomatous
      polyposis coli (APC) gene. Cardamonin also down-regulated intracellular beta
      catenin levels in SW480 cells without affecting its mRNA levels. Interestingly,
      pharmacological inhibition of the proteasome prevented the cardamonin-induced
      down-regulation of beta-catenin. In addition, cardamonin suppressed the
      expression of cyclin D1 and c-myc, which are known beta-catenin/T cell factor
      (TCF)-dependent genes. Moreover, cardamonin inhibited the growth of various colon
      cancer cells and induced G2/M cell cycle arrest in SW480 colon cancer cells.
      These findings indicate that cardamonin is a potential chemotherapeutic agent
      against colon cancer.

PMID- 23538441
TI  - NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and
      extrasynaptic receptors.
AB  - N-methyl-D-aspartate receptors (NMDAR) overactivation is linked to
      neurodegeneration. The current prevailing theory suggests that synaptic and
      extrasynaptic NMDAR (syn- and ex-NMDAR) impose counteracting effects on cell
      fate, and neuronal cell death is mainly mediated by the activation of ex-NMDAR.
      However, several lines of evidence implicate the limitation of this theory. Here,
      we demonstrate that activation of NMDAR bi-directionally regulated cell fate
      through stimulating pro-survival or pro-death signaling. While low-dose NMDA
      preferentially activated syn-NMDAR and stimulated the extracellular signal
      regulated kinase 1/2-cAMP responsive element-binding protein-brain-derived
      neurotrophic factor pro-survival signaling, higher doses progressively activated
      increasing amount of ex-NMDAR along with syn-NMDAR and triggered cell death
      program. Interestingly, the activation of syn- or ex-NMDAR alone did not cause
      measurable cell death. Consistently, activation of syn- or ex-NMDAR alone
      stimulated pro-survival but not pro-death signaling. Next, we found that
      memantine, which was previously identified as an ex-NMDAR blocker, inhibited
      intracellular signaling mediated by syn- or ex-NMDAR. Simultaneous blockade of
      syn- and ex-NMDAR by memantine dose-dependently attenuated NMDAR-mediated death.
      Moreover, long- but not short-term treatment with high-dose NMDA or oxygen
      glucose deprivation triggered cell death and suppressed pro-survival signaling.
      These data implicate that activation of syn- or ex-NMDAR alone is not neurotoxic.
      The degree of excitotoxicity depends on the magnitude and duration of syn- and ex
      NMDAR coactivation. Finally, genome-wide examination demonstrated that the
      activation of syn- and ex-NMDAR lead to significant overlapping rather than
      counteracting transcriptional responses.

PMID- 23538442
TI  - Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by
      decreasing BKCa channel activity.
AB  - Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain
      tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and
      chemotherapy-induced apoptosis accounts for the generally dismal treatment
      outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from
      Bipolaris species, for its promising anticancer activity against human GBM cells
      exhibiting varying degrees of resistance to proapoptotic stimuli. We found that
      OP-A induced marked changes in the dynamic organization of the F-actin
      cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely
      by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel
      activity. Moreover, our results indicated that OP-A induced paraptosis-like cell
      death in GBM cells, which correlated with the vacuolization, possibly brought
      about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum
      (ER). In addition, the OP-A-induced cell death did not involve the activation of
      caspases. We also showed that the expression of BKCa channels colocalized with
      these two organelles (mitochondria and ER) was affected in this programmed cell
      death pathway. Thus, this study reveals a novel mechanism of action associated
      with the anticancer effects of OP-A, which involves the induction of paraptosis
      through the disruption of internal potassium ion homeostasis. Our findings offer
      a promising therapeutic strategy to overcome the intrinsic resistance of GBM
      cells to proapoptotic stimuli.

PMID- 23538443
TI  - Influenza A virus nucleoprotein induces apoptosis in human airway epithelial
      cells: implications of a novel interaction between nucleoprotein and host protein
      Clusterin.
AB  - Apoptosis induction is an antiviral host response, however, influenza A virus
      (IAV) infection promotes host cell death. The nucleoprotein (NP) of IAV is known
      to contribute to viral pathogenesis, but its role in virus-induced host cell
      death was hitherto unknown. We observed that NP contributes to IAV infection
      induced cell death and heterologous expression of NP alone can induce apoptosis
      in human airway epithelial cells. The apoptotic effect of IAV NP was significant
      when compared with other known proapoptotic proteins of IAV. The cell death
      induced by IAV NP was executed through the intrinsic apoptosis pathway. We
      screened host cellular factors for those that may be targeted by NP for inducing
      apoptosis and identified human antiapoptotic protein Clusterin (CLU) as a novel
      interacting partner. The interaction between IAV NP and CLU was highly conserved
      and mediated through beta-chain of the CLU protein. Also CLU was found to
      interact specifically with IAV NP and not with any other known apoptosis
      modulatory protein of IAV. CLU prevents induction of the intrinsic apoptosis
      pathway by binding to Bax and inhibiting its movement into the mitochondria. We
      found that the expression of IAV NP reduced the association between CLU and Bax
      in mammalian cells. Further, we observed that CLU overexpression attenuated NP
      induced cell death and had a negative effect on IAV replication. Collectively,
      these findings indicate a new function for IAV NP in inducing host cell death and
      suggest a role for the host antiapoptotic protein CLU in this process.

PMID- 23538444
TI  - Netrin-1 protects hypoxia-induced mitochondrial apoptosis through HSP27
      expression via DCC- and integrin alpha6beta4-dependent Akt, GSK-3beta, and HSF-1
      in mesenchymal stem cells.
AB  - Netrin (Ntn) has the potential to be successfully applied as an anti-apoptotic
      agent with a high affinity for tissue, for therapeutic strategies of umbilical
      cord blood-derived mesenchymal stem cells (UCB-MSC), although the mechanism by
      which Ntn-1 protects hypoxic injury has yet to be identified. Therefore, the
      present study examined the effect of Ntn-1 on hypoxia-induced UCB-MSC apoptosis,
      as well as the potential underlying mechanisms of its protective effect. Hypoxia
      (72 h) reduced cell viability (MTT reduction, and [(3)H]-thymidine incorporation)
      and cell number, and induced apoptosis (annexin and/or PI positive), which were
      reversed by Ntn-1 (10 ng/ml). Moreover, Ntn-1 decreased the increase of hypoxia
      induced Bax, cleaved caspase-9, and -3, but blocked the decrease of hypoxia
      reduced Bcl-2. Next, in order to examine the Ntn-1-related signaling cascade in
      the protection of hypoxic injury, we analyzed six Ntn receptors in UCB-MSC. We
      identified deleted in colorectal cancer (DCC) and integrin (IN) alpha6beta4,
      except uncoordinated family member (UNC) 5A-C, and neogenin. Among them, IN
      alpha6beta4 only was detected in lipid raft fractions. In addition, Ntn-1 induced
      the dissociation of DCC and APPL-1 complex, thereby stimulating the formation of
      APPL-1 and Akt2 complex. Ntn-1 also reversed the hypoxia-induced decrease of Akt
      and glycogen synthase kinase 3beta (GSK-3beta) phosphorylation, which is involved
      in heat shock factor-1 (HSF-1) expression. Ntn-1-induced phospho-Akt and -GSK
      3beta were inhibited by DCC function-blocking antibody, IN a6b4 function-blocking
      antibody, and the Akt inhibitor. Hypoxia and/or Ntn-1 stimulated heat shock
      protein (HSP)27 expression, which was blocked by HSF-1-specific small interfering
      RNA (siRNA). Furthermore, HSP27-specific siRNA reversed the Ntn-1-induced
      increase of phospho-Akt. Additionally, HSP27-specific siRNA attenuated the Ntn-1
      reduced loss of mitochondrial membrane injury via the inhibition of cytochrome c
      (cyt c) release and formation of cyt c and HSP27 complex. Moreover, the
      inhibition of each signaling protein attenuated Ntn-1-induced blockage of
      apoptosis. In conclusion, Ntn-1-induced HSP27 protected hypoxic injury-related
      UCB-MSC apoptosis through DCC- and IN alpha6beta4-dependent Akt, GSK-3beta, and
      HSF-1 signaling pathways.

PMID- 23538445
TI  - Identification of non-canonical NF-kappaB signaling as a critical mediator of
      Smac mimetic-stimulated migration and invasion of glioblastoma cells.
AB  - As inhibitor of apoptosis (IAP) proteins can regulate additional signaling
      pathways beyond apoptosis, we investigated the effect of the second mitochondrial
      activator of caspases (Smac) mimetic BV6, which antagonizes IAP proteins, on non
      apoptotic functions in glioblastoma (GBM). Here, we identify non-canonical
      nuclear factor-kappaB (NF-kappaB) signaling and a tumor necrosis factor-alpha
      (TNFalpha)/TNF receptor 1 (TNFR1) autocrine/paracrine loop as critical mediators
      of BV6-stimulated migration and invasion of GBM cells. In addition to GBM cell
      lines, BV6 triggers cell elongation, migration and invasion in primary, patient
      derived GBM cells at non-toxic concentrations, which do not affect cell viability
      or proliferation, and also increases infiltrative tumor growth in vivo
      underscoring the relevance of these findings. Molecular studies reveal that BV6
      causes rapid degradation of cellular IAP proteins, accumulation of NIK,
      processing of p100 to p52, translocation of p52 into the nucleus, increased NF
      kappaB DNA binding and enhanced NF-kappaB transcriptional activity.
      Electrophoretic mobility shift assay supershift shows that the NF-kappaB DNA
      binding subunits consist of p50, p52 and RelB further confirming the activation
      of the non-canonical NF-kappaB pathway. BV6-stimulated NF-kappaB activation leads
      to elevated mRNA levels of TNFalpha and additional NF-kappaB target genes
      involved in migration (i.e., interleukin 8, monocyte chemoattractant protein 1,
      CXC chemokine receptor 4) and invasion (i.e., matrix metalloproteinase-9).
      Importantly, inhibition of NF-kappaB by overexpression of dominant-negative
      IkappaBalpha superrepressor prevents the BV6-stimulated cell elongation,
      migration and invasion. Similarly, specific inhibition of non-canonical NF-kappaB
      signaling by RNA interference-mediated silencing of NIK suppresses the BV6
      induced cell elongation, migration and invasion as well as upregulation of NF
      kappaB target genes. Intriguingly, pharmacological or genetic inhibition of the
      BV6-stimulated TNFalpha autocrine/paracrine loop by the TNFalpha-blocking
      antibody Enbrel or by knockdown of TNFR1 abrogates BV6-induced cell elongation,
      migration and invasion. By demonstrating that the Smac mimetic BV6 at non-toxic
      concentrations promotes migration and invasion of GBM cells via non-canonical NF
      kappaB signaling, our findings have important implications for the use of Smac
      mimetics as cancer therapeutics.

PMID- 23538446
TI  - The E3 ubiquitin ligase Itch regulates tumor suppressor protein RASSF5/NORE1
      stability in an acetylation-dependent manner.
AB  - Ras association (RalGDS/AF-6) domain family member RASSF5 is a non-enzymatic RAS
      effector super family protein, known to be involved in cell growth regulation.
      Expression of RASSF5 is found to be extinguished by promoter hypermethylation in
      different human cancers, and its ectopic expression suppresses cell proliferation
      and tumorigenicity. Interestingly, this role in tumorigenesis has been confounded
      by the fact that regulation at molecular level remains unclear and many
      transformed cells actually display elevated RASSF5 expression. Here, we
      demonstrate that E3 ubiquitin ligase Itch is a unique binding partner of RASSF5.
      Itch can interact with PPxY motif in RASSF5 both in vivo and in vitro through its
      WW domains. Importantly, the overexpression of Itch induces RASSF5 degradation by
      poly-ubiquitination via 26S proteasome pathway. In addition, our results indicate
      that the elevated levels of RASSF5 found in tumor cells due to acetylation, which
      restricts its binding to Itch and results in a more stable inert protein.
      Inhibition of RASSF5 acetylation permits its interaction with Itch and provokes
      proteasomal degradation. These data suggest that apart from promoter methylation,
      hyperacetylation could also be downregulating RASSF5 function in different human
      cancer. Finally, results from functional assays suggest that the overexpression
      of wild type, not the ligase activity defective Itch negatively regulate RASSF5
      mediated G1 phase transition of cell cycle as well as apoptosis, suggesting that
      Itch alone is sufficient to alter RASSF5 function. Collectively, the present
      investigation identifies a HECT class E3 ubiquitin ligase Itch as a unique
      negative regulator of RASSF5, and suggests the possibility that acetylation as a
      potential therapeutic target for human cancer.

PMID- 23538448
TI  - Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)
      1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin
      A.
AB  - Eight N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes were
      efficiently prepared as sulfur analogues of Tubastatin A and thus evaluated as
      new HDAC6 inhibitors. All compounds exhibited potency against HDAC6, and four of
      them were active in the nanomolar range (IC(50) = 1.9-22 nM). Further analysis
      revealed that the sulfone derivatives (designated as Tubathians) are superior to
      their non-oxidized sulfide analogues, and the two most active sulfones showed
      good to excellent HDAC6 selectivity compared to all other HDAC isoform classes.

PMID- 23538447
TI  - Apoptosis of osteosarcoma cultures by the combination of the cyclin-dependent
      kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor.
AB  - Osteosarcoma (OS) is an aggressive bone cancer typically observed in adolescents
      and young adults. Metastatic relapse accounts primarily for treatment failure,
      and obstacles to improving cure rates include a lack of efficacious agents. Our
      studies show apoptosis of OS cells prepared from localized and metastatic tumors
      by a novel drug combination: SCH727965 (SCH), a cyclin-dependent kinase
      inhibitor, and NVP-AUY922 (AUY) or other heat shock protein 90 inhibitor. SCH and
      AUY induced apoptosis when added simultaneously to cells and when AUY was added
      to and removed from cells before SCH addition. Sequential treatment was most
      effective when cells received AUY for ~12 h and when SCH was presented to cells
      immediately after AUY removal. The apoptotic protein Bax accumulated in
      mitochondria of cotreated cells but was primarily cytosolic in cells receiving
      either agent alone. Additional data show that SCH and AUY cooperatively induce
      the apoptosis of other sarcoma cell types but not of normal osteoblasts or
      fibroblasts, and that SCH and AUY individually inhibit cell cycle progression
      throughout the cell cycle. We suggest that the combination of SCH and AUY may be
      an effective new strategy for treatment of OS.

PMID- 23538450
TI  - Validity and reliability of a 1500-m lap-time collection method using public
      videos.
AB  - The collection of retrospective lap times from video footage is a potentially
      useful research tool to analyze the pacing strategies in any number of
      competitive events. The aim of this study was to validate a novel method of
      obtaining running split-time data from publically available video footage. Videos
      of the 1500-m men's final from the 2004 and 2008 Olympics, 2005 and 2009 World
      Championships, and 2010 European Championships were obtained from the YouTube Web
      site, and split times were collected from all competitors using frame-by-frame
      playback. The typical error of video split times ranged between 0.02 s and 0.11 s
      for the 4 laps when compared with official split times. Video finishing times
      were also similar to official finishing times (typical error of 0.04 s). The
      method was shown to be highly reliable with a typical error of 0.02 s when the
      same video was analyzed on 2 occasions separated by 8 mo. Video data of track
      races are widely available; however, camera angles are not always perpendicular
      to the start/finish line, and some slower athletes may cross the line after the
      camera has panned away. Nevertheless, the typical errors reported here show that
      when appropriate camera angles are available this method is both valid and
      reliable. 

PMID- 23538449
TI  - Alcohol screening scores and 90-day outcomes in patients with acute lung injury.
AB  - OBJECTIVES: The effects of excess alcohol consumption (alcohol misuse) on
      outcomes in patients with acute lung injury have been inconsistent, and there are
      no studies examining this association in the era of low tidal volume ventilation
      and a fluid conservative strategy. We sought to determine whether validated
      scores on the Alcohol Use Disorders Identification Test that correspond to past
      year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol
      misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor
      outcomes in patients with acute lung injury. DESIGN: Secondary analysis. SETTING:
      The Acute Respiratory Distress Syndrome Network, a consortium of 12 university
      centers (44 hospitals) dedicated to the conduct of multicenter clinical trials in
      patients with acute lung injury. SUBJECTS: Patients meeting consensus criteria
      for acute lung injury enrolled in one of three recent Acute Respiratory Distress
      Syndrome Network clinical trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Of 1,133 patients enrolled in one of three Acute Respiratory Distress
      Syndrome Network studies, 1,037 patients had an Alcohol Use Disorders
      Identification Test score available for analysis. Alcohol misuse was common with
      70 (7%) of patients having Alcohol Use Disorders Identification Test scores in
      zone 3 and 129 (12%) patients in zone 4. There was a U-shaped association between
      validated Alcohol Use Disorders Identification Test zones and death or persistent
      hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in
      zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a
      multiple logistic regression model, there was a significantly higher odds of
      death or persistent hospitalization in patients having Alcohol Use Disorders
      Identification Test zone 4 compared with those in zone 2 (adjusted odds ratio
      1.70; 95% confidence interval 1.00, 2.87; p = 0.048). CONCLUSIONS: Severe but not
      mild to moderate alcohol misuse is independently associated with an increased
      risk of death or persistent hospitalization at 90 days in acute lung injury
      patients.

PMID- 23538452
TI  - A change for the better.

PMID- 23538453
TI  - Thoracic cirtometry in children with Duchenne muscular dystrophy--expansion of
      the method.
AB  - BACKGROUND: Thoracic cirtometry is a simple and accessible technique to evaluate
      chest mobility during forced breathing. However, it does not allow for the
      assessment of compensatory movements commonly used by people with chronic
      diseases, such Duchenne muscular dystrophy (DMD). DMD is a condition
      characterized by progressive and irreversible degeneration of the musculoskeletal
      system. OBJECTIVES: To expand the method of thoracic cirtometry to allow for the
      assessment of compensatory movements; to analyze the reliability of the tool; and
      to describe thoracic mobility of children with DMD during deep breathing. METHOD:
      Sixty boys, 30 with DMD (10.1+/-0.5 years) and 30 healthy controls (9.5+/-0.6
      years) participated in the study. The expanded thoracic cirtometry was organized
      in two phases: 1. the body could move freely, allowing the assessment of
      compensatory movements (free thoracic cirtometry) and 2. the body without
      compensatory movements, allowing for the direct study of the movements of the
      chest (guided thoracic cirtometry). This method includes videotaping and
      systematic observation of body movements using descriptive and numeric data. We
      investigated reliability of these measures in both groups. RESULTS: Measures of
      axial and the xiphoid thoracic cirtometry (both free and guided) showed excellent
      reliability. All measures were significantly different between groups. In DMD
      boys, free thoracic cirtometry presented a greater value of chest expansion when
      compared with the guided measures, which probably occurred due to compensatory
      movements. The most commons were movements of the head, shoulder and torso.
      CONCLUSIONS: The expanded thoracic cirtometry method showed excellent reliability
      and achieved the objectives of determining measures of chest mobility and
      compensatory movements during deep breath. We suggested its use in the
      respiratory evaluation of children with DMD.

PMID- 23538454
TI  - Relationship between frailty and respiratory function in the community-dwelling
      elderly.
AB  - OBJECTIVE: To evaluate the impact of frailty on respiratory function in a
      community- dwelling elderly. METHOD: 51 community-dwelling elderly were evaluated
      (mean age of 73+/-6 years), being 29 men (56.7%) and 22 women (43.3%). We collect
      the following variables: sociodemographic characteristics, frailty phenotype,
      pulmonary function test and assessment of the respiratory muscles using an analog
      manometer. The statistical analysis was performed using the Kolmogorov and
      Smirnov tests, one-way ANOVA, Paired Student's t-test and Pearson correlation
      coefficient (p<0.05). RESULTS: There were no statistically significant between
      group differences among the frail group (FG=9.8%), pre-frail group (PG=47.1%) and
      non-frail group (NG=43.1%), in relation to anthropometric, demographic and
      spirometric data. Regarding to the maximum inspiratory and expiratory pressures
      (MIP and MEP), statistically significant between-group differences were observed
      among the three groups, being these pressures significantly lower in the FG and
      PG compared to the NG. With regards to the obtained and predicted values, the FG
      and PG showed statistically significant difference (p=0.004). The PG showed
      positive correlations between the MIP and MEP with the values of hand grip
      strength (r=0.7). The NG showed positive correlation between the MEP and the
      values of physical activity level (r=0.7). CONCLUSIONS: The study demonstrated
      that maximal respiratory pressures may decrease according to the frailty
      condition among the non-frail, pre-frail and frail elderly. Furthermore, it also
      indicated a positive correlation between inspiratory muscle strength, expiratory
      muscle strength and hand grip strength in pre-frail elderly. Further
      investigation with regards to prevention or intervention programs that
      incorporate actions to minimize the loss of respiratory function are necessary in
      order to reverse or prevent the progression of the frailty condition.

PMID- 23538455
TI  - Effect of treadmill gait training on static and functional balance in children
      with cerebral palsy: a randomized controlled trial.
AB  - BACKGROUND: Treadmill gait training as a therapeutic resource in the
      rehabilitation of children with cerebral palsy has recently been the focus of
      many studies; however, little is still known regarding its effect on static and
      functional balance in children. OBJECTIVE: The aim of the present study was to
      compare the effects of treadmill training and over ground gait training in
      children with cerebral palsy. METHOD: A randomized controlled trial with blinded
      evaluator was conducted with children with cerebral palsy between three and 12
      years of age categorized in Levels I to III of the Gross Motor Function
      Classification System. Assessments were performed before and after the
      intervention and involved the Berg balance scale as well as the determination of
      oscillations from the center of pressure in the anteroposterior and mediolateral
      directions with eyes open and closed. The experimental group was submitted to
      treadmill training and the control group performed gait training over the ground.
      The intervention consisted of two 30-minute sessions per week for seven weeks.
      RESULTS: Both groups exhibited better functional balance after the protocol. The
      experimental group had higher Berg balance scale scores and exhibited lesser
      mediolateral oscillation with eyes open in comparison to the control group.
      CONCLUSIONS: Treadmill training had a greater effect on functional balance and
      mediolateral oscillation in comparison to over ground gait training in children
      with cerebral palsy. TRIAL REGISTRATION: RBR-5v3kg9.(Brazilian Registry of
      Clinical Trials).

PMID- 23538456
TI  - Wrist electrogoniometry: are current mathematical correction procedures effective
      in reducing crosstalk in functional assessment?
AB  - BACKGROUND: The recording of human movement is an essential requirement for
      biomechanical, clinical, and occupational analysis, allowing assessment of
      postural variation, occupational risks, and preventive programs in physical
      therapy and rehabilitation. The flexible electrogoniometer (EGM), considered a
      reliable and accurate device, is used for dynamic recordings of different joints.
      Despite these advantages, the EGM is susceptible to measurement errors, known as
      crosstalk. There are two known types of crosstalk: crosstalk due to sensor
      rotation and inherent crosstalk. Correction procedures have been proposed to
      correct these errors; however no study has used both procedures in clinical
      measures for wrist movements with the aim to optimize the correction. OBJECTIVE:
      To evaluate the effects of mathematical correction procedures on: 1) crosstalk
      due to forearm rotation, 2) inherent sensor crosstalk; and 3) the combination of
      these two procedures. METHOD: 43 healthy subjects had their maximum range of
      motion of wrist flexion/extension and ulnar/radials deviation recorded by EGM.
      The results were analyzed descriptively, and procedures were compared by
      differences. RESULTS: There was no significant difference in measurements before
      and after the application of correction procedures (P<0.05). Furthermore, the
      differences between the correction procedures were less than 5 degrees  in most
      cases, having little impact on the measurements. CONCLUSIONS: Considering the
      time-consuming data analysis, the specific technical knowledge involved, and the
      inefficient results, the correction procedures are not recommended for wrist
      recordings by EGM.

PMID- 23538457
TI  - Profile and scientific output analysis of physical therapy researchers with
      research productivity fellowship from the Brazilian National Council for
      Scientific and Technological Development.
AB  - OBJECTIVE: To describe the profile and the scientific output of physical
      therapists researchers holding a research productivity fellowship (PQ) from the
      Brazilian National Council of Scientific and Technological Development (Conselho
      Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq). METHOD: This is a
      cross-sectional study, which has evaluated the Lattes Curriculum of all PQ
      physiotherapy researchers registered at CNPq holding a research productivity
      fellowship in the period of 2010. The variables analyzed were: gender, geographic
      and institutional distribution, duration since doctorate defense, research
      productivity fellowship level, scientific output until 2010 and the H index in
      Scopus((r)) and ISI databases. RESULTS: A total of 55 PQ from the CNPq were
      identified in the area of knowledge of Physical Therapy and Occupational Therapy,
      being 81.8% from the Southeast region of Brazil. They were predominantly female
      (61.8%), with research productivity fellowship level PQ2 (74.5%), and with
      average time since doctorate defense of 10.1 (+/-4.1) years. A total of 2.381
      articles were published, with average of 42.5 (+/-18.9) articles/researcher. The
      average of articles published after doctorate defense was 39.40 (+/-18.9)
      articles/researchers with a mean output of 4.2 (+/-2.0) articles/year. We found
      304 articles indexed in the Scopus((r)) database with 2.463 citations, and 222
      articles indexed in the Web of Science with 1.805 citations. The articles were
      published in 481 journals, being 244 (50.7%) of them listed on JCR-web. The
      researchers presented a median 5 of the H index in the Scopus((r)) database, and
      a median 3 in ISI. CONCLUSION: The scientific output of the researchers with
      research productivity fellowship in the field of physical therapy stands out in
      their indicators, since the figures are very promising for a relatively young
      area and as it can be observed by the amount of published articles and citations
      obtained by the national and international research community.

PMID- 23538458
TI  - Recruitment rate, feasibility and safety of power training in individuals with
      Parkinson's disease: a proof-of-concept study.
AB  - BACKGROUND: It has been suggested that power training should be implemented in
      interventions in Parkinson's disease (PD). However, it is necessary to determine
      the feasibility and safety of training rapid movements in such individuals.
      OBJECTIVES: To determine the rate of recruitment of potential participants, the
      rate of attendance at training sessions, the levels of adherence to the
      intervention, and the rate of adverse events. METHOD: Patients with PD, users of
      the national public health system underwent power training of the lower limb
      muscles three times a week for 10 weeks. The number of people who were screened
      and recruited was recorded, as well as the rate of attendance at the training
      sessions and adherence to the intervention protocol. Safety was assessed by the
      presence of adverse events, pain, number of falls, and risk of injury associated
      with the intervention. RESULTS: Over the course of eight months, 62 individuals
      were screened and only 13 completed the program. The rates of attendance and
      adherence were 88% and 97%, respectively. There were no adverse events during
      training. Two participants reported joint pain and one reported falls during the
      training period. CONCLUSIONS: The recruitment rate was low due to the subjects'
      difficulties with transportation and lack of interest. The high rates of
      adherence and attendance and the absence of adverse events suggest that power
      training is feasible and safe in PD.

PMID- 23538459
TI  - Strength deficit of knee flexors is dependent on hip position in adults with
      chronic hemiparesis.
AB  - BACKGROUND: The extent to which muscle length affects force production in paretic
      lower limb muscles after stroke in comparison to controls has not been
      established. OBJECTIVES: To investigate knee flexor strength deficits dependent
      on hip joint position in adults with hemiparesis and compare with healthy
      controls. METHOD: a cross-sectional study with ten subjects with chronic (63+/-40
      months) hemiparesis with mild to moderate lower limb paresis (Fugl-Meyer score
      26+/-3) and 10 neurologically healthy controls. Isometric knee flexion strength
      with the hip positioned at 90 degrees  and 0 degrees  of flexion was assessed
      randomly on the paretic and non-paretic side of hemiparetic subjects and healthy
      controls. Subjects were asked to perform a maximal isometric contraction
      sustained for four seconds and measured by a dynamometer. The ratio of knee
      flexor strength between these two hip positions was calculated: Hip 0 degrees
      /Hip 90 degrees . Also, locomotor capacity was evaluated by the timed up and go
      test and by walking velocity over 10 meters. RESULTS: In subjects with
      hemiparesis, absolute knee flexion torque decreased (p<0.001) with the hip in
      extension (at 0 degrees ). The ratio of knee flexor torque Hip 0 degrees /Hip 90
      degrees  on the paretic side in hemiparetics was lower than in controls (p=0.02).
      CONCLUSIONS: Weakness dependent on joint position is more significant in the
      paretic lower limb of adults with hemiparesis when compared to controls. More
      attention should be given to lower limb muscle strengthening exercises in
      individuals with stroke, with emphasis on the strengthening exercises in
      positions in which the muscle is shortened.

PMID- 23538460
TI  - Choroidal and cutaneous metastasis from gastric adenocarcinoma.
AB  - Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal
      cancer was found in only 4% in patients with uveal metastasis. Choroidal
      metastasis from gastric cancer was reported in two cases in earlier literature.
      The frequency of gastric cancer as a primary lesion was 6% in cutaneous
      metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric
      cancers. We report a patient with gastric adenocarcinoma who presented with
      visual disorder in his left eye and skin pain on his head as his initial
      symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous
      metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of
      oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective
      to reduce the primary gastric lesion and almost all the metastatic lesions.

PMID- 23538461
TI  - Estimation of left ventricular stroke volume by impedance cardiography: its
      relation to the aortic reservoir.
AB  - Impedance cardiography is a non-invasive technique used to estimate left
      ventricular (LV) stroke volume (SV) using the change in thoracic impedance
      (DeltaZ). It remains controversial, partly because impedance cardiographic
      parameters have not been successfully related to haemodynamic events. We
      hypothesized that the change in DeltaZ may be proportional to the variation in
      thoracic (primarily aortic) blood volumes. Nine anaesthetized and ventilated dogs
      were divided into the following two groups: the 'aortic volume group' (n = 5), in
      which aortic and IVC (inferior vena caval) dimensions were measured
      ultrasonically; and the 'reservoir volume group', in which aortic and IVC
      reservoir volumes were calculated using the reservoir-wave model. Measurements
      were made in control conditions, in the presence of nitroprusside and methoxamine
      and after volume loading. In both the aortic volume group and the reservoir
      volume group, the maximal rate of increase in DeltaZ [(dZ/dt)max] strongly
      correlated with the maximal rate of change in aortic/reservoir blood volume (R(2)
      = 0.85 and 0.95, respectively), which in turn was proportional to the LV SV. The
      LV and IVC contributions to DeltaZ were small in control conditions (~5 and 1%,
      respectively), but the LV contribution increased slightly (to 7%) with
      administration of methoxamine and after volume loading (to 10%). It is concluded
      that the change in thoracic impedance (DeltaZ) during the cardiac cycle is
      proportional to the change in aortic reservoir (i.e. Windkessel) volume, which
      provides a mechanistic explanation for previously demonstrated good correlations
      with standard measures of cardiac output. 

PMID- 23538462
TI  - Cyclo-oxygenase-1 or -2-mediated metabolism of arachidonic acid in endothelium
      dependent contraction of mouse arteries.
AB  - This study aimed to determine whether the cyclo-oxygenase (COX) substrate
      arachidonic acid (AA) evokes endothelium-dependent contraction and, if so, the
      specific COX isoform(s) involved and whether prostacyclin (prostaglandin I2;
      PGI2), a mediator of endothelium-derived vasoconstrictor activity, can be
      generated in medial smooth muscle from the intermediate COX product prostaglandin
      H2 (PGH2) that might diffuse from the endothelium. Aortae and/or carotid arteries
      were isolated from C57BL/6 mice or those lacking one of the two COX isoforms (COX
      1(-/-) or COX-2(-/-)) for functional and/or biochemical analyses. Results showed
      that in vessels from C57BL/6 mice, exogenous AA evoked not only endothelium
      dependent production of the PGI2 metabolite 6-keto-PGF1alpha, but also
      contractions reduced by thromboxane-prostanoid receptor antagonism or endothelial
      denudation. The minimal concentration for AA to evoke contraction was 0.3 MUm, a
      level thought to activate only COX-2. However, neither the contraction nor 6-keto
      PGF1alpha production was altered in vessels from COX-2(-/-) mice, while both were
      reduced in COX-1(-/-) counterparts. In vessels from COX-1(-/-) mice, AA also
      caused minor contractions that were sensitive to non-selective COX inhibition.
      Real-time PCR showed that like COX-1, COX-2 mainly existed in the endothelium,
      but it was unaltered in COX-1(-/-) mice. Also, we noted that in endothelium
      denuded aortae, PGH2 generated PGI2 as in intact vessels. These results
      demonstrate a predominant role for COX-1 and suggest that in the given mouse
      arteries, metabolites from either COX isoform cause contraction. Moreover, our
      results imply that some of the PGI2 involved in vasoconstrictor activity of
      endothelial COX-mediated metabolism could possibly be generated from PGH2 in
      medial smooth muscle. 

PMID- 23538463
TI  - Constrained optimization of metabolic cost in human hopping.
AB  - Constrained optimization of metabolic cost/distance travelled largely predicts
      the gait parameters selected by humans during walking and running. This study
      evaluates whether this is also the case for human hopping. Hop frequency (f),
      height (h) and metabolic energy expenditure were measured in partly constrained
      (f, h or hop speed, s = fh, specified), fully constrained (both f and h
      specified) and unconstrained conditions (neither f nor h specified) for 4 min
      trials. Hop frequency and height were also measured in frequency-constrained (f
      specified), fully constrained (maximal height and f specified) and unconstrained
      conditions for 15 s trials. Metabolic cost surfaces were constructed from
      experimental data from the 4 min trials, and the least costly behaviour for each
      constraint was calculated. Subjects selected the same height-frequency pattern
      for all three partly constrained conditions because the metabolic cost/height
      surface for hopping was a slope with no observed minimum. The heights selected
      for the 15 s frequency-constrained trials were only slightly lower than maximal,
      the optimal behaviour predicted by constrained optimization of metabolic
      cost/height. This supports the hypothesis that constrained optimization of
      metabolic cost largely predicts movement selection during hopping. However,
      subjects often chose noticeably lower than optimal heights and higher than
      optimal frequencies during partly constrained and unconstrained conditions for
      the 4 min trials. It appears that they selected heights and frequencies that
      incurred a slightly greater metabolic cost/height in order to reduce metabolic
      cost/time to a level they could comfortably sustain for 4 min. 

PMID- 23538464
TI  - Serum visfatin levels do not increase in post-menopausal women with metabolic
      syndrome.
AB  - BACKGROUND: The aim of this study was to determine the serum visfatin levels in
      post-menopausal (PM) women with and without metabolic syndrome (MS) and to
      understand the correlation between serum visfatin levels and various other
      hormonal and metabolic parameters. MATERIALS-METHODS: We conducted a prospective
      cross-sectional study including 17 PM women with MS and a control group of 51 PM
      women without MS. MS was defined according to the National Cholesterol Education
      Program Adult Treatment Panel III. RESULTS: Women with MS had statistically
      significantly higher fasting blood glucose, HDL, triglycerides, insulin,
      homeostasis model assessment of insulin resistance, and SHBG levels when compared
      to women without MS. Estradiol, high sensitivity C-reactive protein, and free
      testosterone levels were higher in the MS group, but there was no statistically
      significant difference between the two groups. Visfatin levels did not differ
      between the two groups. There was no correlation between serum visfatin levels
      and other parameters. CONCLUSIONS: There was no association between serum
      visfatin levels and MS in PM women.

PMID- 23538465
TI  - Endocrinology and art. The hospitality of Abraham--Francesco Solimena called
      Abate Ciccio (1657-1747).

PMID- 23538466
TI  - [Climacteric and sexuality].

PMID- 23538467
TI  - Comparison of nuclear grade and immunohistochemical features in situ and invasive
      components of ductal carcinoma of breast.
AB  - PURPOSE: To compare the prognostic and predictive features between in situ and
      invasive components of ductal breast carcinomas. METHODS: We selected 146
      consecutive breast samples with ductal carcinoma in situ (DCIS) associated with
      adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and
      immunohistochemical expression of estrogen receptor (ER), progesterone receptor
      (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6),
      and epidermal growth factor receptor (EGFR) in both components, in situ and
      invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and
      IBC were classified in molecular surrogate types determined by the
      immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple
      positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and
      triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and
      luminal B was not performed due to statistical purposes. Correlations between the
      categories in the two groups were made using the Spearman correlation method.
      RESULTS: There was a significant correlation between nuclear grade (p<0.0001),
      expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of
      EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and
      IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a
      significant association with the triple-negative phenotype in IBC, but a negative
      association among DCIS. CONCLUSIONS: Our results suggest that classical
      prognostic and predictive features of IBC are already determined in the
      preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma
      may be different from the precursor lesions.

PMID- 23538468
TI  - Quality of life and menopausal symptoms in women with liver transplants.
AB  - PURPOSE: To assess quality of life and climacteric symptoms in women with and
      without liver transplants. METHODS: This was a cross-sectional study of 52 women
      undergoing follow-up at a university hospital in southeastern Brazil from
      February 4th, 2009 to January 5th, 2011. Twenty-four of these women were 35 years
      old or older and had undergone liver transplantation at least one year before
      study entry. The remaining 28 women had no liver disease and were matched by age
      and menstrual patterns to the patients with transplants. The abbreviated version
      of the World Health Organization (WHOQOL-BREF) questionnaire was used to assess
      quality of life. Menopausal symptoms were assessed using the Menopause Rating
      Scale (MRS). Statistical analysis was carried out by Student's t-test, Mann
      Whitney test and analysis of variance. Correlations between MRS and the WHOQOL
      BREF were established by correlation coefficients. RESULTS: The mean age of the
      women included in the study was 52.2 (+/- 10.4) years and the mean time since
      transplantation was 6.1 (+/- 3.3) years. Women with liver transplants had better
      quality of life scores in the environment domain (p=0.01). No difference was
      noted between the two groups in any domain of the MRS. For women in the
      comparison group, there was a strongly negative correlation between somatic
      symptoms in the MRS and the physical domain of the WHOQOL-BREF (p<0.01; r=-0.8).
      In contrast, there was only a moderate association for women with liver
      transplants (p<0.01; r=-0.5). CONCLUSIONS: Women with liver transplants had
      better quality of life scores in the domain related to environment and did not
      exhibit more intense climacteric symptoms than did those with no liver disease.
      Climacteric symptoms negatively influenced quality of life in liver transplant
      recipients, although less intensely than in women without a history of liver
      disease.

PMID- 23538469
TI  - Frequency of fear of needles and impact of a multidisciplinary educational
      approach towards pregnant women with diabetes.
AB  - PURPOSE: To evaluate the frequency of fear of needles and the impact of a
      multidisciplinary educational program in women with pre-gestational and
      gestational diabetes taking insulin during pregnancy. METHODS: The short Diabetes
      Fear of Injecting and Self-testing Questionnaire (D-FISQ), composed by two
      subscales that access fear of self injection (FSI) and fear of self testing
      (FST), was administered twice during pregnancy to 65 pregnant women with pre
      gestational and gestational diabetes: at the first endocrine consult and within
      the last two weeks of pregnancy or postpartum. An organized multidisciplinary
      program provided diabetes education during pregnancy. Statistical analysis was
      carried out by Wilcoxon and McNemar tests and Spearman correlation. A p<0.05 was
      considered to be significant. RESULTS: Data from the short D-FISQ questionnaire
      shows that 43.1% of pregnant women were afraid of needles in the first
      evaluation. There was a significant reduction in scores for FSI and FST subscales
      between the first and second assessments (first FSI 38.5% compared with second
      12.7%, p=0.001; first FST 27.7% compared with second FST 14.3%, p=0.012).
      CONCLUSIONS: The fear of needles is common in pregnant women on insulin therapy
      and an organized multidisciplinary educational diabetes program applied during
      pregnancy reduces scores of such fear.

PMID- 23538470
TI  - Assessment of pelvic floor by three-dimensional-ultrasound in primiparous women
      according to delivery mode: initial experience from a single reference service in
      Brazil.
AB  - PURPOSE: To evaluate changes to the pelvic floor of primiparous women with
      different delivery modes, using three-dimensional ultrasound. METHODS: A
      prospective cross-sectional study on 35 primiparae divided into groups according
      to the delivery mode: elective cesarean delivery (n=10), vaginal delivery (n=16),
      and forceps delivery (n=9). Three-dimensional ultrasound on the pelvic floor was
      performed on the second postpartum day with the patient in a resting position. A
      convex volumetric transducer (RAB4-8L) was used, in contact with the large labia,
      with the patient in the gynecological position. Biometric measurements of the
      urogenital hiatus were taken in the axial plane on images in the rendering mode,
      in order to assess the area, anteroposterior and transverse diameters, average
      thickness, and avulsion of the levator ani muscle. Differences between groups
      were evaluated by determining the mean differences and their respective 95%
      confidence intervals. The proportions of levator ani muscle avulsion were
      compared between elective cesarean section and vaginal birth using Fisher's exact
      test. RESULTS: The mean areas of the urogenital hiatus in the cases of vaginal
      and forceps deliveries were 17.0 and 20.1 cm(2), respectively, versus 12.4 cm(2)
      in the Control Group (elective cesarean). Avulsion of the levator ani muscle was
      observed in women who underwent vaginal delivery (3/25), however there was no
      statistically significant difference between cesarean section and vaginal
      delivery groups (p=0.5). CONCLUSION: Transperineal three-dimensional ultrasound
      was useful for assessing the pelvic floor of primiparous women, by allowing
      pelvic morphological changes to be differentiated according to the delivery mode.

PMID- 23538471
TI  - Anatomical and functional characteristics of the pelvic floor in nulliparous
      women submitted to three-dimensional endovaginal ultrasonography: case control
      study and evaluation of interobserver agreement.
AB  - PURPOSE: To determine anatomical and functional pelvic floor measurements
      performed with three-dimensional (3-D) endovaginal ultrasonography in
      asymptomatic nulliparous women without dysfunctions detected in previous dynamic
      3-D anorectal ultrasonography (echo defecography) and to demonstrate the
      interobserver reliability of these measurements. METHODS: Asymptomatic
      nulliparous volunteers were submitted to echo defecography to identify dynamic
      dysfunctions, including anatomical (rectocele, intussusceptions,
      entero/sigmoidocele and perineal descent) and functional changes (non-relaxation
      or paradoxical contraction of the puborectalis muscle) in the posterior
      compartment and assessed with regard to the biometric index of levator hiatus,
      pubovisceral muscle thickness, urethral length, anorectal angle, anorectal
      junction position and bladder neck position with the 3-D endovaginal
      ultrasonography. All measurements were compared at rest and during the Valsalva
      maneuver, and perineal and bladder neck descent was determined. The level of
      interobserver agreement was evaluated for all measurements. RESULTS: A total of
      34 volunteers were assessed by echo defecography and by 3-D endovaginal
      ultrasonography. Out of these, 20 subjects met the inclusion criteria. The 14
      excluded subjects were found to have posterior dynamic dysfunctions. During the
      Valsalva maneuver, the hiatal area was significantly larger, the urethra was
      significantly shorter and the anorectal angle was greater. Measurements at rest
      and during the Valsalva maneuver differed significantly with regard to anorectal
      junction and bladder neck position. The mean values for normal perineal descent
      and bladder neck descent were 0.6 cm and 0.5 cm above the symphysis pubis,
      respectively. The intraclass correlation coefficient ranged from 0.62-0.93.
      CONCLUSIONS: Functional biometric indexes, normal perineal descent and bladder
      neck descent values were determined for young asymptomatic nulliparous women with
      the 3-D endovaginal ultrasonography. The method was found to be reliable to
      measure pelvic floor structures at rest and during Valsalva, and might therefore
      be suitable for identifying dysfunctions in symptomatic patients.

PMID- 23538472
TI  - Depression with postpartum onset: a prospective cohort study in women undergoing
      elective cesarean section in Brasilia, Brazil.
AB  - PURPOSE: It was to determine the prevalence of depressive symptoms in a sample of
      puerperal women from Brasilia, Brazil, distinguishing cases with onset after
      delivery from those already present during pregnancy. METHODS: A prospective
      cohort study with convenience sampling of patients submitted to elective cesarean
      section at two private hospitals. As an instrument for assessing depressive
      symptoms, the Edinburgh Postnatal Depression Scale with cutoff >13 was applied
      shortly before delivery and four to eight weeks after childbirth. RESULTS: Among
      the 107 women who completed the study, 11 (10.3%) had significant depressive
      symptoms during pregnancy and 12 (11.2%) during the postpartum period. Among the
      12 patients with postpartum symptoms, 6 had symptoms during pregnancy, so that
      5.6% of the sample had postpartum onset of depression. The higher overall
      frequency of depression was significantly among single women than among married
      women (p=0.04), a fact mainly due to a higher frequency of single women
      experiencing persistent depressive symptoms both before and after delivery
      (p=0.002). The risk of depression was not influenced by age, parity or
      educational level. CONCLUSION: Women with depression identified during the
      postpartum period comprise a heterogeneous group, in which symptoms may have
      started before pregnancy, during pregnancy or after childbirth. In this sample,
      half of the postpartum depression cases already presented symptoms during late
      pregnancy. Since depression can arise before and after childbirth, it may have
      different etiologies and, therefore, a different response to treatment, a
      possibility that should be considered by clinicians and researchers.

PMID- 23538473
TI  - [Clinical use for anti-mullerian hormone in gynecology].
AB  - Anti-mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of
      primary, pre-antral and small antral ovarian follicles and its clinical
      applicability has been recently demonstrated by several studies. Prediction of
      the response to ovarian stimulation for in vitro fertilization corresponds to the
      most frequent utilization of AMH in clinical practice, being routinely assessed
      in many services to identify subgroups of women susceptible to a poor response or
      to Ovarian Hyperstimulation Syndrome. There are great perspectives that AMH may
      be applicable to the individual determination of risk for iatrogenic gonadal
      injury in women with neoplasms who will be submitted to chemotherapy. It is also
      probable that AMH assessment will be included in protocols for the investigation
      of amenorrhea and oligomenorrhea, since AMH levels are increased in Polycystic
      Ovary Syndrome, reduced in premature ovarian failure and normal in other
      conditions such as hyperprolactinemia and hypogonadotropic hypogonadism. It is
      possible that AMH will be utilized in the future for the prediction of age at
      menopause and of reproductive prognosis, providing solid bases for pre-conceptive
      and contraceptive counseling.

PMID- 23538474
TI  - Myocardial perfusion imaging in patients with a recent, normal exercise test.
AB  - AIM: To investigate the added value of myocardial perfusion scintigraphy imaging
      (MPI) in consecutive patients with suspected coronary artery disease (CAD) and a
      recent, normal exercise electrocardiography (ECG). METHODS: This study was a
      retrospective analysis of consecutive patients referred for MPI during a 2-year
      period from 2006-2007 at one clinic. All eligible patients were suspected of
      suffering from CAD, and had performed a satisfactory bicycle exercise test (i.e.,
      peak heart rate > 85% of the expected, age-predicted maximum) within 6 mo of
      referral, their exercise ECG was had no signs of ischemia, there was no exercise
      limiting angina, and no cardiac events occurred between the exercise test and
      referral. The patients subsequently underwent a standard 2-d, stress-rest
      exercise MPI. Ischemia was defined based on visual scoring supported by
      quantitative segmental analysis (i.e., sum of stress score > 3). The results of
      cardiac catheterization were analyzed, and clinical follow up was performed by
      review of electronic medical files. RESULTS: A total of 56 patients fulfilled the
      eligibility criteria. Most patients had a low or intermediate ATPIII pre-test
      risk of CAD (6 patients had a high pre-test risk). The referral exercise test
      showed a mean Duke score of 5 (range: 2 to 11), which translated to a low post
      exercise risk in 66% and intermediate risk in 34%. A total of seven patients were
      reported with ischemia by MPI. Three of these patients had high ATPIII pre-test
      risk scores. Six of these seven patients underwent cardiac catheterization, which
      showed significant stenosis in one patient with a high pre-test risk of CAD, and
      indeterminate lesions in three patients (two of whom had high pre-test risk
      scores). With MPI as a gate keeper for catheterization, no significant,
      epicardial stenosis was observed in any of the 50 patients (0%, 95% confidence
      interval 0.0 to 7.1) with low to intermediate pre-test risk of CAD and a negative
      exercise test. No cardiac events occurred in any patients within a median follow
      up period of > 1200 d. CONCLUSION: The added diagnostic value of MPI in patients
      with low or intermediate risk of CAD and a recent, normal exercise test is
      marginal.

PMID- 23538475
TI  - Computational method for calculating fluorescence intensities within three
      dimensional structures in cells.
AB  - The use of fluorescence microscopy is central to cell biology in general, and
      essential to many fields (e.g., membrane traffic) that rely upon it to identify
      cellular locations of molecules under study and the extent to which they co
      localize with others. Rigorous localization or co-localization data require
      quantitative image analyses that can vary widely between fields and laboratories.
      While most published data use two-dimensional images, there is an increasing
      appreciation for the advantages of collecting three-dimensional data sets. These
      include the ability to evaluate the entire cell and avoidance of focal plane
      bias. This is particularly important when imaging and quantifying changes in
      organelles with irregular borders and which vary in appearance between cells in a
      population, e.g., the Golgi. We describe a method developed for quantifying
      changes in signal intensity of one protein within any three-dimensional
      structure, defined by the presence of a different marker. We use as examples of
      this method the quantification of adaptor recruitment to transmembrane protein
      cargos at the Golgi though it can be directly applied to any site in the cell.
      Together, these advantages facilitate rigorous statistical testing of differences
      between conditions, despite variations in organelle structure, and we believe
      that this method of quantification of fluorescence data can be productively
      applied to a wide array of experimental questions.

PMID- 23538476
TI  - Sedimentary Records of Non-Aroclor and Aroclor PCB mixtures in the Great Lakes.
AB  - Three sediment cores from Lake Ontario, Lake Erie and Indiana Harbor Ship Canal
      were collected, segmented and analyzed for Aroclor and non-Aroclor
      polychlorinated biphenyl congeners (PCBs). PCBs associated with the commercially
      produced Aroclor mixtures 1248 and 1254 dominate the sediment signal and the sum
      of all congeners (SigmaPCB) peaks in concentration and accumulation around 1970
      in the Great Lakes. This trend is very similar to Aroclor production history. In
      the Indiana Harbor Ship Canal, PCBs appear around 1935 and remain at very high
      levels between 1940 and 1980, probably reflecting the history of use at the
      nearby steel mill. In contrast, the non-Aroclor PCBs in the Lake Ontario and IHSC
      sediment cores, including PCB11 and heavily chlorinated congeners PCB206, 207,
      208 and 209 reach a peak in the 1950s, decline and peak again in the 1970s or in
      the early 1980s. All five congeners have been previously measured in commercial
      paint pigment. PCB11 was found to peak about 5 years later than SigmaPCBs, and is
      probably associated with the production or use history of diarylide yellow
      pigments. The temporal distribution profiles of these non-Aroclor PCBs are well
      correlated with the production history of paint pigments and dyes. Although it is
      well known that the production of Aroclor PCBs is preserved in Great Lakes
      sediments, this study is the first to show that production of non-Aroclors are
      also preserved in the sediments as a record of long term trends in environmental
      exposure.

PMID- 23538477
TI  - Line Transect and Triangulation Surveys Provide Reliable Estimates of the Density
      of Kloss' Gibbons (Hylobates klossii) on Siberut Island, Indonesia.
AB  - Estimating population densities of key species is crucial for many conservation
      programs. Density estimates provide baseline data and enable monitoring of
      population size. Several different survey methods are available, and the choice
      of method depends on the species and study aims. Few studies have compared the
      accuracy and efficiency of different survey methods for large mammals,
      particularly for primates. Here we compare estimates of density and abundance of
      Kloss' gibbons (Hylobates klossii) using two of the most common survey methods:
      line transect distance sampling and triangulation. Line transect surveys (survey
      effort: 155.5 km) produced a total of 101 auditory and visual encounters and a
      density estimate of 5.5 gibbon clusters (groups or subgroups of primate social
      units)/km2. Triangulation conducted from 12 listening posts during the same
      period revealed a similar density estimate of 5.0 clusters/km2. Coefficients of
      variation of cluster density estimates were slightly higher from triangulation
      (0.24) than from line transects (0.17), resulting in a lack of precision in
      detecting changes in cluster densities of <66 % for triangulation and <47 % for
      line transect surveys at the 5 % significance level with a statistical power of
      50 %. This case study shows that both methods may provide estimates with similar
      accuracy but that line transects can result in more precise estimates and allow
      assessment of other primate species. For a rapid assessment of gibbon density
      under time and financial constraints, the triangulation method also may be
      appropriate.

PMID- 23538479
TI  - Anterior chamber bleeding after laser peripheral iridotomy.
AB  - IMPORTANCE: To our knowledge, this is the first study to describe the correlation
      of anterior chamber bleeding after laser peripheral iridotomy (LPI) and
      antiplatelet therapy. OBJECTIVE: To determine the incidence and amount of
      anterior chamber bleeding after laser peripheral iridotomy in patients whose
      condition is suggestive of primary angle-closure glaucoma (PACS) who continued
      their antiplatelet or anticoagulant treatment before undergoing LPI compared with
      when they discontinued treatment. DESIGN AND SETTING: A prospective controlled
      trial. PATIENTS: Patients with suspected bilateral primary angle-closure and no
      other ocular disease who take antiplatelet or anticoagulant medications regularly
      (from January 2010-October 2011) were enrolled. MAIN OUTCOME AND MEASURE: The
      incidence of anterior chamber bleeding with and without antiplatelet and
      anticoagulant therapy. RESULTS: A total of 104 patients (208 eyes) participated
      in the study. Thirty-six eyes (34.6%) in the treated and untreated arms bled. The
      amount of bleeding did not differ significantly when the patient was on or off
      antiplatelet or anticoagulant treatment, nor did the immediate postprocedure mean
      intraocular pressure (P = .13). The type of antiplatelet or anticoagulant, total
      laser energy, age, sex, or color of irides were not risk factors for increased
      bleeding (P = .156 for all parameters). CONCLUSIONS: No indication was noted for
      discontinuing these medications before a high-powered pulsed laser peripheral
      iridotomy.

PMID- 23538481
TI  - Two-month angioscopic evaluation of superficial femoral artery treated with
      paclitaxel-coated nitinol drug-eluting stent.

PMID- 23538480
TI  - Hepatitis B and inflammatory bowel disease: role of antiviral prophylaxis.
AB  - Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in
      patients receiving immunosuppression has been widely described as being
      associated with significant morbidity and mortality unless anti-viral prophylaxis
      is administered. Treatment in inflammatory bowel disease (IBD) patients has
      changed in recent years and immunosuppression and biological therapies are now
      used more frequently than before. Although current studies have reported an
      incidence of hepatitis B in inflammatory bowel disease patients similar to that
      in the general population, associated liver damage remains an important concern
      in this setting. Liver dysfunction may manifest in several ways, from a subtle
      change in serum aminotransferase levels to fulminant liver failure and death.
      Patients undergoing double immunosuppression are at a higher risk, and
      reactivation usually occurs after more than one year of treatment. As preventive
      measures, all IBD patients should be screened for HBV markers at diagnosis and
      those who are positive for the hepatitis B surface antigen should receive
      antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV
      reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide
      analogues due to their better resistance profile. In patients with occult or
      resolved HBV, viral reactivation does not appear to be a relevant issue and
      regular DNA determination is recommended during immunosuppression therapy.
      Consensus guidelines on this topic have been published in recent years. The
      prevention and management of HBV infection in IBD patients is addressed in this
      review in order to address practical recommendations.

PMID- 23538482
TI  - Physiologic functions of cyclophilin D and the mitochondrial permeability
      transition pore.
AB  - This review focuses on the role of cyclophilin D (CypD) as a prominent mediator
      of the mitochondrial permeability transition pore (MPTP) and subsequent effects
      on cardiovascular physiology and pathology. Although a great number of reviews
      have been written on the MPTP and its effects on cell death, we focus on the
      biology surrounding CypD itself and the non-cell death physiologic functions of
      the MPTP. A greater understanding of the physiologic functions of the MPTP and
      its regulation by CypD will likely suggest novel therapeutic approaches for
      cardiovascular disease, both dependent and independent of programmed necrotic
      cell death mechanisms.  

PMID- 23538483
TI  - Global cardiovascular device innovation: Japan-USA synergies: Harmonization by
      Doing (HBD) program, a consortium of regulatory agencies, medical device
      industry, and academic institutions.
AB  - BACKGROUND: Global medical devices have become more popular, but investment money
      for medical device development is not easily available in the market. Worldwide
      health-care budget constraints mean that efficient medical device development has
      become essential. To achieve efficient development, globalization is a key to
      success. Spending large amounts of money in different regions for medical device
      development is no longer feasible. METHODS AND RESULTS: In order to streamline
      processes of global medical device development, an academic, governmental, and
      industrial consortium, called the Harmonization by Doing program, has been set
      up. The program has been operating between Japan and the USA since 2003. The
      program has 4 working groups: (1) Global Cardiovascular Device Trials; (2) Study
      on Post-Market Registry; (3) Clinical Trials; and (4) Infrastructure and
      Methodology Regulatory Convergence and Communication. Each working group has as
      its goals the achievement of speedy and efficient medical device development in
      Japan and the USA. The program has held multiple international meetings to deal
      with obstacles against efficient medical device development. CONCLUSIONS: This
      kind of program is very important to deliver novel medical devices. Involvement
      of physicians in this type of activity is also very helpful to achieve these
      goals.

PMID- 23538484
TI  - Scottish country dance: benefits to functional ability in older women.
AB  - The effects of long-term participation in Scottish country dance on body
      composition, functional ability, and balance in healthy older females were
      examined. Participants were grouped into dancers and physically active nondancers
      (ages 60-70 and 70-80 for both groups). Physical activity, body composition (body
      mass index, skinfold thickness, waist-to-hip ratio), functional ability (6-min
      walk distance, 6-m walk time, 8-ft up-and-go time, lower body flexibility,
      shoulder flexibility), and static balance were measured. Younger dancers and
      physically active nondancers had similar 6-min walk distance, 6-m walk time, and
      8-ft up-and-go time results; however, while older dancers performed similarly to
      younger dancers, older physically active nondancers performed poorer than their
      younger counterparts (p < .05). Body composition and static balance were the same
      for all groups. Regular physical activity can maintain body composition and
      postural stability with advancing age; however, Scottish country dance can delay
      the effects of aging on locomotion-related functional abilities. 

PMID- 23538486
TI  - Transfection of Kasumi-1 cells with a new type of polymer carriers loaded with
      miR-155 and antago-miR-155.
AB  - Previous studies have demonstrated functional roles for microRNAs (miRNAs) in
      various aspects of normal and malignant hematopoiesis, including lineage
      commitment, differentiation, apoptosis and maturation. In vivo delivery of naked
      DNA, oligonucleotides and miRNAs is complicated by their low stability, rapid
      degradation and inefficient delivery into target cells. In our experiments, we
      used a new type of polymer carriers to monitor the effects of miR-155 and antago
      miR-155 on the morphology and genetics of Kasumi-1 cells. We obtained platelet
      like cells from leukemic cells, and detected the expression of platelet marker
      genes after transfection with antago-miR-155. Our findings suggest that
      administration of miR mimics or antago-miRs as therapeutic agents is a desirable
      goal for future treatment of hematologic malignancies and that polymer-based
      carriers for the delivery of miR mimics or antago-miRs may provide a solution to
      the challenges of standard miR delivery approaches.

PMID- 23538485
TI  - Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of
      rats.
AB  - AIM: To investigate the effects of mitofusin-2 (MFN2) on insulin sensitivity and
      its potential targets in the liver of rats fed with a high-fat diet (HFD).
      METHODS: Rats were fed with a control or HFD for 4 or 8 wk, and were then
      infected with a control or an MFN2 expressing adenovirus once a week for 3 wk
      starting from the 9(th) wk. Blood glucose (BG), plasma insulin and insulin
      sensitivity of rats were determined at end of the 4(th) and 8(th) wk, and after
      treatment with different amounts of MFN2 expressing adenovirus (10(8), 10(9) or
      10(10) vp/kg body weight). BG levels were measured by Accu-chek Active Meter.
      Plasma insulin levels were analyzed by using a Rat insulin enzyme-linked
      immunosorbent assay kit. Insulin resistance was evaluated by measuring the
      glucose infusion rate (GIR) using a hyperinsulinemic euglycemic clamp technique.
      The expression or phosphorylation levels of MFN2 and essential molecules in the
      insulin signaling pathway, such as insulin receptor (INSR), insulin receptor
      substrate 2 (IRS2), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT2)
      and glucose transporter type 2 (GLUT2) was assayed by quantitative real-time
      polymerase chain reaction and Western-blotting. RESULTS: After the end of 8 wk,
      the body weight of rats receiving the normal control diet (ND) and the HFD was
      not significantly different (P > 0.05). Compared with the ND group, GIR in the
      HFD group was significantly decreased (P < 0.01), while the levels of BG,
      triglycerides (TG), total cholesterol (TC) and insulin in the HFD group were
      significantly higher than those in the ND group (P < 0.05). Expression of MFN2
      mRNA and protein in liver of rats was significantly down-regulated in the HFD
      group (P < 0.01) after 8 wk of HFD feeding. The expression of INSR, IRS2 and
      GLUT2 were down-regulated markedly (P < 0.01). Although there were no changes in
      PI3K-P85 and AKT2 expression, their phosphorylation levels were decreased
      significantly (P < 0.01). After intervention with MFN2 expressing adenovirus for
      3 wk, the expression of MFN2 mRNA and protein levels were up-regulated (P <
      0.01). There was no difference in body weight of rats between the groups. The
      levels of BG, TG, TC and insulin in rats were lower than those in the Ad group (P
      < 0.05), but GIR in rats infected with Ad-MFN2 was significantly increased (P <
      0.01), compared with the Ad group. The expression of INSR, IRS2 and GLUT2 was
      increased, while phosphorylation levels of PI3K-P85 and AKT2 were increased (P <
      0.01), compared with the Ad group. CONCLUSION: HFDs induce insulin resistance,
      and this can be reversed by MFN2 over-expression targeting the insulin signaling
      pathway.

PMID- 23538487
TI  - Two-way model with random cell sizes.
AB  - We consider inference for row effects in the presence of possible interactions in
      a two-way fixed effects model when the numbers of observations are themselves
      random variables. Let Nij be the number of observations in the (i, j) cell, piij
      be the probability that a particular observation is in that cell and MUij be the
      expected value of an observation in that cell. We assume that the {Nij } have a
      joint multinomial distribution with parameters n and {piij }. Then MUi . = Sigma
      jpiijMUij /Sigma jpiij is the expected value of a randomly chosen observation in
      the ith row. Hence, we consider testing that the MUi . are equal. With the {piij
      } unknown, there is no obvious sum of squares and F-ratio computed by the widely
      available statistical packages for testing this hypothesis. Let Yi .. be the
      sample mean of the observations in the ith row. We show that Yi .. is an MLE of
      MUi ., is consistent and is conditionally unbiased. We then find the asymptotic
      joint distribution of the Yi .. and use it to construct a sensible asymptotic
      size alpha test of the equality of the MUi . and asymptotic simultaneous (1 -
      alpha) confidence intervals for contrasts in the MUi ..

PMID- 23538489
TI  - Boron and nucleic acid chemistries: merging the best of both worlds.
AB  - At the intersection of nucleic acid and boron chemistries lies a thriving world
      of possibilities. During the past decades, the merging of these research domains
      has led to fascinating discoveries in different fields ranging from material to
      medical sciences. In recent years the interplay of these two worlds has gained a
      lot of attention, as can be judged by the increasing number of articles in which
      boron and nucleic acids stand out for their potential medicinal, biotechnological
      or analytical applications. In this review, we present an outline of this
      crossroads by focusing on both the interaction of boronated compounds with
      nucleic acids and the modification of nucleic acids by boron containing moieties.

PMID- 23538490
TI  - Crown Ether Host-Rotaxanes as Cytotoxic Agents.
AB  - Highly toxic bacterial ionophores are commonly used in veterinary medicine, but
      their therapeutic index is too narrow for human usage. With the goal of
      developing ionophores with a broader therapeutic index, we constructed highly
      derivatized synthetic ionophores. The toxicities of crown ether host-rotaxanes
      (CEHR's) against the SKOV-3 cell line were measured. The effect of Mg2+ or Ca2+
      on toxicity was explored because changes in the intracellular concentration of
      these cations can cause cell death through apoptosis. We found Boc-CEHR is highly
      toxic and Arg-CEHR is slightly less toxic with IC50 values of 0.5 MUM and 6 MUM,
      respectively, in standard growth medium. Increasing the concentration of Ca2+
      resulted in greater toxicity of the CEHRs, whereas increasing the concentration
      of Mg2+ was less effective on reducing IC50. Cell death occurs mainly through
      apoptosis. Although preliminary, these results suggest that the CEHRs deliver
      Ca2+ and perhaps Mg2+ into cells inducing apoptosis.

PMID- 23538488
TI  - Epigenetic regulation of retinal development and disease.
AB  - Epigenetic regulation, including DNA methylation, histone modifications, and
      chromosomal organization, is emerging as a new layer of transcriptional
      regulation in retinal development and maintenance. Guided by intrinsic
      transcription factors and extrinsic signaling molecules, epigenetic regulation
      can activate and/or repress the expression of specific sets of genes, therefore
      playing an important role in retinal cell fate specification and terminal
      differentiation during development as well as maintaining cell function and
      survival in adults. Here, we review the major findings that have linked these
      mechanisms to the development and maintenance of retinal structure and function,
      with a focus on ganglion cells and photoreceptors. The mechanisms of epigenetic
      regulation are highly complex and vary among different cell types. Understanding
      the basic principles of these mechanisms and their regulatory pathways may
      provide new insight into the pathogenesis of retinal diseases associated with
      transcription dysregulation, and new therapeutic strategies for treatment.

PMID- 23538491
TI  - Healthcare commissioners need clearer expectations and longer funding rounds,
      says NHS regulator.

PMID- 23538493
TI  - Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF
      alpha on tight junction proteins and signaling pathways in intestinal epithelial
      cells.
AB  - Intestinal barrier dysfunction is pivotal in the etiology of inflammatory bowel
      diseases. Combined clinical and endoscopic remission ("mucosal healing") in
      patients who received anti-TNF-alpha therapies suggests restitution of the
      intestinal barrier, but the mechanisms involved are largely unknown. We therefore
      investigated the impact of the anti-TNF-alpha antibody adalimumab on barrier
      function in two in vitro models. Combined stimulation of Caco-2 and T-84 cells
      with interferon-gamma and TNF-alpha resulted in a significant decrease of
      transepithelial electrical resistance (TEER) within 6 h that was prevented by
      adalimumab in concentrations down to 100 ng/ml. Adalimumab furthermore
      antagonized the appearance of irregular membrane undulations and prevented
      internalization of tight junction proteins upon cytokine exposure. In addition,
      TNF-alpha induced a downregulation of claudin-1, claudin-2, claudin-4, and
      occludin as well as activation of phosphatidylinositol 3-kinase signaling in T-84
      but not Caco-2 cells, which was reversed by adalimumab. At the signaling level,
      adalimumab prevented increased phosphorylation of myosin light chain as well as
      activation of p38 MAPK and NF-kappaB accompanying the decline in TEER in both
      model systems. Pharmacological inhibition of NF-kappaB signaling partially
      prevented the TNF-alpha-induced TEER loss, whereas inhibition of p38 worsened
      barrier dysfunction in Caco-2 but not T-84 cells. Taken together, these data
      demonstrate that adalimumab prevents barrier dysfunction induced by TNF-alpha
      both functionally and structurally as well as at the level of signal
      transduction. Barrier protection might therefore constitute a novel mechanism how
      anti-TNF-alpha therapy contributes to epithelial restitution and tissue repair in
      inflammatory bowel diseases.

PMID- 23538492
TI  - Emerging neuropeptide targets in inflammation: NPY and VIP.
AB  - The enteric nervous system (ENS), referred to as the "second brain," comprises a
      vast number of neurons that form an elegant network throughout the
      gastrointestinal tract. Neuropeptides produced by the ENS play a crucial role in
      the regulation of inflammatory processes via cross talk with the enteric immune
      system. In addition, neuropeptides have paracrine effects on epithelial
      secretion, thus regulating epithelial barrier functions and thereby
      susceptibility to inflammation. Ultimately the inflammatory response damages the
      enteric neurons themselves, resulting in deregulations in circuitry and gut
      motility. In this review, we have emphasized the concept of neurogenic
      inflammation and the interaction between the enteric immune system and enteric
      nervous system, focusing on neuropeptide Y (NPY) and vasoactive intestinal
      peptide (VIP). The alterations in the expression of NPY and VIP in inflammation
      and their significant roles in immunomodulation are discussed. We highlight the
      mechanism of action of these neuropeptides on immune cells, focusing on the key
      receptors as well as the intracellular signaling pathways that are activated to
      regulate the release of cytokines. In addition, we also examine the direct and
      indirect mechanisms of neuropeptide regulation of epithelial tight junctions and
      permeability, which are a crucial determinant of susceptibility to inflammation.
      Finally, we also discuss the potential of emerging neuropeptide-based therapies
      that utilize peptide agonists, antagonists, siRNA, oligonucleotides, and
      lentiviral vectors.

PMID- 23538495
TI  - Mechanisms of pyrethroid resistance in Haematobia irritans (Muscidae) from Mato
      Grosso do Sul state, Brazil.
AB  - Horn fly resistance to pyrethroid insecticides occurs throughout Brazil, but
      knowledge about the involved mechanisms is still in an incipient stage. This
      survey was aimed to identify the mechanisms of horn fly resistance to
      cypermethrin in Mato Grosso do Sul state, Brazil. Impregnated filter paper
      bioassays using cypermethrin, synergized or not with piperonyl butoxide (PBO) and
      triphenyl phosphate (TPP), were conducted from March 2004 to June 2005 in horn
      fly populations (n = 33) from all over the state. All populations were highly
      resistant to cypermethrin, with resistance factors (RF) ranging from 89.4 to
      1,020.6. Polymerase chain reaction (PCR) assays to detect the knockdown
      resistance (kdr) mutation also were performed in 16 samples. The kdr mutation was
      found in 75% of the tested populations, mostly with relatively low frequencies
      (<20%), and was absent in some highly resistant populations. Addition of TPP did
      not significantly reduce the LC50 in any population. However, PBO reduced LC50s
      above 40-fold in all tested populations, resulting in RFs <= 10 in most cases.
      Horn fly resistance to cypermethrin is widespread in the state, being primarily
      caused by an enhanced activity of P450 mono-oxygenases and secondarily by reduced
      target site sensitivity. 

PMID- 23538494
TI  - Anti-melanin-concentrating hormone treatment attenuates chronic experimental
      colitis and fibrosis.
AB  - Fibrosis represents a major complication of several chronic diseases, including
      inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge
      despite several recent therapeutic advances. Melanin-concentrating hormone (MCH)
      is a hypothalamic neuropeptide shown to regulate appetite and energy balance.
      However, accumulating evidence suggests that MCH has additional biological
      effects, including modulation of inflammation. In the present study, we examined
      the efficacy of an MCH-blocking antibody in treating established, dextran sodium
      sulfate-induced experimental colitis. Histological and molecular analysis of
      mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal
      restitution and lower colonic expression of several proinflammatory cytokines, as
      well as fibrogenic genes, including COL1A1. In parallel, they spared collagen
      deposits seen in the untreated mice, suggesting attenuated fibrosis. These
      findings raised the possibility of perhaps direct effects of MCH on
      myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate
      expression of the MCH receptor MCHR1 in alpha-smooth muscle actin(+)
      subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell
      line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic
      modulator by potentiating the effects of IGF-1 and TGF-beta on proliferation and
      collagen production. Thus, by virtue of combined anti-inflammatory and anti
      fibrotic effects, blocking MCH might represent a compelling approach for treating
      IBD.

PMID- 23538496
TI  - Molecular detection of Ehrlichia canis in dogs from the Pantanal of Mato Grosso
      State, Brazil.
AB  - The present study evaluated the presence of Ehrlichia DNA in the blood samples of
      320 dogs from the urban and rural areas of the municipality of Pocone, Pantanal
      region, Mato Grosso state, by Polymerase Chain Reaction (PCR), targeting the
      ehrlichial dsb gene. Risk factors for infection in dogs were also evaluated.
      Forty-eight (15%, 95% CI: 11.4-19.5%) dogs were positive: 25 (15.6%, 95% CI: 10.4
      22.2%) from the urban area and 23 (14.4%, 95% CI: 9.3-20.8%) from the rural area
      (P > 0.05). Partial DNA sequence obtained from PCR products of 18 samples from
      the urban area and 16 samples from the rural area were 100% identical to E. canis
      from Brazil and the USA. This study reports the first E. canis molecular
      detection in dogs from the northern Pantanal region.

PMID- 23538497
TI  - Leishmania (Leishmania) hertigi in a porcupine (Coendou sp.) found in Brasilia,
      Federal District, Brazil.
AB  - Studies report the occurrence of Leishmania (Leishmania) hertigi in northern
      states of Brazil. In the present investigation, we describe the isolation of L.
      (L.) hertigi from a porcupine (Coendou sp.) found in Brasilia, Federal District,
      center-west region of Brazil. During a study on canine visceral leishmaniasis
      conducted in the city of Brasilia, Federal District, a porcupine was found dead
      on a public road. The animal was identified and fragments of intact skin and
      spleen were collected for isolation of parasite in the culture. This report of
      the occurrence of L. hertigi in another part of Brazil may help establish the
      distribution of this parasite in the country. Further studies are needed to
      better understand the role of L. hertigi in the pathology and pathogenesis of
      leishmaniasis and its survival in mammals and possible vectors.

PMID- 23538498
TI  - Diagnosis and isolation of Toxoplasma gondii in horses from Brazilian
      slaughterhouses.
AB  - This study aimed to investigate anti-Toxoplasma gondii antibodies and to isolate
      the parasite from the brains of horses processed at slaughterhouses in Brazil. We
      collected brain and blood samples from 398 horses of various ages, from six
      Brazilian states. Serum samples were evaluated by indirect fluorescent antibody
      test (IFAT cut-off titre >= 1:64), and brains were submitted to mouse bioassay.
      Among the 398 horses, positivity for T. gondii was identified in 46 (11.6%) by
      IFAT and in 14 (3.5%) by mouse bioassay. In 12 of those 14 bioassays, mice were
      positive only by IFAT (cut-off titre >= 1:16), T. gondii being isolated in the
      remaining two. Using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis of 18S rDNA to differentiate among T. gondii,
      Neospora caninum, and Sarcocystis neurona, we found that two of the 14 brains
      were positive for T. gondii only. For genotyping of the two isolates and the PCR
      positive brain, we performed PCR-RFLP based on 13 markers, and SAG2 all samples
      were Toxoplasma gondii type I. Collectively, IFAT of horse sera and mouse
      bioassay identified positivity in 60 (15%) of the samples. Our results show that
      some horses sent to slaughter in Brazil have been exposed to T. gondii. 

PMID- 23538499
TI  - Control of infective larvae of gastrointestinal nematodes in heifers using
      different isolates of nematophagous fungi.
AB  - The effect of different nematophagous fungi [Duddingtonia flagrans (AC001 and
      CG722) and Monacrosporium thaumasium (NF34)] with regard to controlling infective
      larvae (L3) of nematodes after gastrointestinal transit in female cattle (3/4
      Holstein * Zebu) was evaluated. A total of 24 pubescent female cattle were used,
      weighing approximately 320 kg each one. There were three treatment groups, each
      contained six animals that received 150 g of pellets (0.2 g of mycelium), orally
      in a single dose, in a sodium alginate matrix containing mycelial mass of the
      fungus D. flagrans (AC001 or CG722) or M. thaumasium (NF34); and one control
      group (without fungi). Fecal samples were collected from the animals at intervals
      of 12, 15, 18, 21, 24, 48, and 72 hours. At the end of 17 days, the L3 not
      subjected to predation were recovered by means of the Baermann method. The fungal
      isolates tested were capable of destroying the L3 after gastrointestinal transit.
      It was observed that within 72 hours, the isolates AC001, CG722, and NF34 showed
      a higher predatory activity (81.2%, 97.3%, and 98.3%, respectively). The results
      justify the need for studies in the field, and over longer intervals, in order to
      observe the efficiency of the fungus D. flagrans, or even M. thaumasium, for
      environmental control over nematodes in naturally infected cattle.

PMID- 23538500
TI  - Identification of Cryptosporidium species and genotypes in dairy cattle in
      Brazil.
AB  - In this study, we identified Cryptosporidium species and genotypes present in
      dairy cattle in the central region of Sao Paulo state, Brazil. Fecal specimens
      were collected from 200 animals (100 calves and 100 cows) in ten dairy farms.
      Fecal samples were examined using microscopic examination (ME), enzyme
      immunoassay (EIA) and polymerase chain reaction (PCR). Cryptosporidium species
      and genotypes were determined by restriction fragment length polymorphism (RFLP)
      or DNA sequencing analysis of the SSU-rRNA and GP60 genes. The occurrence of
      Cryptosporidium spp. infection was 14% (28/200). The occurrence in calves (26%)
      was significantly higher than in cows (2%). Of the 27 Cryptosporidium-positive
      specimens submitted to genotyping, C. andersoni was identified in 23 (85.1%), C.
      bovis in three (11.1%), and the zoonotic C. parvum subtype IIaA15G2R1 in one
      (3.7%). The study demonstrates that Cryptosporidium spp. infection was common and
      widespread in dairy cattle in this region and that calves have a high prevalence
      of C. andersoni. Furthermore, the presence of C. parvum subtype IIaA15G2R1
      indicates that dairy calves from this region should be considered a potential
      source of zoonotic Cryptosporidium oocysts.

PMID- 23538501
TI  - Health assessment of the oyster Crassostrea rhizophorae on the southern coast of
      Bahia, northeastern Brazil.
AB  - This study investigated the health of natural stocks of the oyster Crassostrea
      rhizophorae on the southern coast of Bahia in northeastern Brazil, during summer
      and winter 2010, at three localities (sampling points) in the estuaries of the
      Marau (Camamu Bay) and Graciosa rivers. A total of 180 oysters (30/sampling
      point/season) were examined macroscopically for the presence of pathogens and
      anatomical changes. The specimens were subsequently fixed in Davidson solution,
      processed for paraffin embedding, sectioned and stained with Harris' hematoxylin
      and eosin. Histological analysis revealed the presence of Rickettsia-like
      organisms (RLOs), Ancistrocoma, Trichodina, Sphenophrya, Nematopsis, Urastoma,
      Bucephalus in the sporocyst phase, a nonspecific metacercaria, and a metacestode
      of genus Tylocephalum. The prevalence of infection was low except for parasitism
      by Nematopsis sp. which also caused histopathological changes. The presence of
      Bucephalus sp. caused parasitic castration. These two pathogens significantly
      affect the health of C. rhizophorae.

PMID- 23538502
TI  - Endoparasitic infections in dogs from rural areas in the Lobos District, Buenos
      Aires province, Argentina.
AB  - Dogs are definite hosts for several zoonotic helminthes and protozoan. Rural
      areas from the Lobos District in the northeast of Buenos Aires province,
      Argentina, are mainly used for livestock activity, increasing in this way the
      number of dogs on farms as well as the human risk of parasitic infections. The
      aims of this research were to evaluate the endoparasitic infections in dogs from
      farms in the Lobos District and analyze their zoonotic importance as well as
      several risk practices and habits of the rural population. Forty-two dog fecal
      samples obtained in 21 farms were analyzed through coproparasitological methods
      and coproantigen tests, which resulted in an overall parasite prevalence of
      69.05% and 80.95% of the parasitized farms. The most frequent parasites were
      Trichuris vulpis and Eucoleus aerophila (26.19%), Echinococcus granulosus
      (19.05%), Uncinaria stenocephala and coccids (14.29%). The analysis of
      epidemiological files showed several habits of the rural population considered as
      risk factors associated with the presence of fecal samples parasitized and the
      presence of E. granulosus on the farms. It is clear that people involved with the
      farms studied were exposed to several helminthes that could cause serious
      diseases like cystic echinococcosis, which can become an important public health
      issue and affect the economy worldwide.

PMID- 23538503
TI  - Acaricides efficiency on Rhipicephalus (Boophilus) microplus from Bahia state
      North-Central region.
AB  - The cattle tick Rhipicephalus (Boophilus) microplus is responsible for major
      losses in the Brazilian livestock, mainly due to reduction in cattle productive
      performance. Resistance development to major classes of acaricide widely used
      nowadays has been extensively reported, as well as the occurrence of residues
      from these compounds in animal products and the environment. This study aimed to
      evaluate the efficiency of acaricides on R. (B.) microplus collected from rural
      properties in the North-Central region of Bahia State. Ticks were collected in
      several cattle farms in the cited region, and an in vitro acaricide efficiency
      assay was performed based on the immersion of ticks in acaricide solutions made
      according to manufacturers' recommendations. The results obtained in the
      experiments indicated varying degrees of efficiency of the several bases studied,
      with the products benzofenilurea, macrocyclic lactone and fipronil showing the
      highest levels of efficiency, 100%, 100% and 97.34%, respectively. It was
      possible to conclude that, for the region studied, there are different degrees of
      commercial acaricides efficiency, and many present less than 95% effectiveness,
      value determined as acceptable by the Brazilian legislation. 

PMID- 23538504
TI  - Parasites of four ornamental fish from the Chumucui River (Braganca, Para,
      Brazil).
AB  - The objective of the present study was to evaluate the parasite fauna of four
      species of ornamental fish collected in the Chumucui River, municipality of
      Braganca, Para, Brazil. From June 2006 to December 2007. Fishes (n=307) belonging
      to four species were collected, including 23 specimens of Moenkhausia
      sanctaefilomenae (redeye tetra), 37 Carnegiella strigata (marbled hatchetfish), 7
      Chilodus punctatus (spotted headstander), and 240 Astyanax bimaculatus (twospot
      astyanax). The parasites found belonged to three taxa: monogeneans in the gills,
      nematodes (larvae of Capillaria sp. and Contracaecum sp.) in the digestive tract
      and liver and acanthocephalans (Quadrigyrus torquatus, Q. brasiliensis and Q.
      nickoli) in the stomach and intestine. Astyanax bimaculatus presented higher
      prevalence of acanthocephalans in the wet season, and lower prevalence of
      nematodes in the dry season. The possible importance of these parasites in the
      exportation of ornamental fish is discussed.

PMID- 23538505
TI  - Prevalence of Oestrus ovis (Diptera: Oestridae) in sheep from the Sao Paulo
      Central region, Brazil.
AB  - The heads of 139 slaughtered sheep were examined with the aim of determining
      Oestrus ovis prevalence and infestation intensity in the central region of the
      State of Sao Paulo, Brazil. Heads from slaughtered sheep were examined and the
      first (L1), second (L2) and third (L3) O. ovis larval instars were recovered from
      the nasal and sinus cavities. O. ovis larvae were detected in 13.7% of the sheep
      analyzed. The monthly mean intensity of infestation ranged from 1 to 10.2 larvae
      per infested head, with general mean intensity of 4.5 larvae/infested head. Of
      the total of 85 larvae, 21.2% were L1, 37.6% L2 and 41.2% L3. In conclusion, all
      different O. ovis larvae instars were recovered from slaughtered animals, which
      demonstrates the existence of favorable climatic conditions for the fly activity
      and larval development of O. ovis in sheep raised in the Central region of the
      State of Sao Paulo.

PMID- 23538506
TI  - Multicolor patterning using holographic woodpile photonic crystals at visible
      wavelengths.
AB  - High-quality woodpile structures with photonic band gaps in the visible
      wavelength range were fabricated using a single prism holographic lithography
      technique. Woodpile structures were prepared to have a rod diameter of 160 nm, a
      lateral periodicity of 240 nm, and an axial periodicity of 300 nm, which is the
      smallest feature size for three-dimensional nanopatterned structures. A
      multicolor patterning method was used to vary the degree of crosslinking in the
      negative photoresist. These woodpile structures showed enhanced fluorescence due
      to a large surface area and the presence of bicontinuous interconnected pores.

PMID- 23538508
TI  - Effects of ritobegron (KUC-7483), a novel beta3-adrenoceptor agonist, on both rat
      bladder function following partial bladder outlet obstruction and on rat salivary
      secretion: a comparison with the effects of tolterodine.
AB  - The objective of this study was to investigate the effects of the beta3
      adrenoceptor (AR) agonist ritobegron on rat bladder function following partial
      bladder outlet obstruction and on rat salivary secretion. In addition, the
      effects of ritobegron were compared with those of the anti-muscarinic agent
      tolterodine. After a 6-week partial bladder outlet obstruction (BOO), drug
      effects on bladder functions were evaluated using cystometrography. Effects on
      carbachol (CCh)-induced salivary secretion were evaluated in urethane
      anesthetized rats. Ritobegron significantly decreased the frequency of non
      voiding contractions (NVC), while both ritobegron and tolterodine each
      significantly decreased the amplitude of NVC. Ritobegron had no effect on either
      the micturition pressure (MP) or the residual volume (RV). In contrast,
      tolterodine dose-dependently decreased MP and increased RV. Ritobegron had no
      effect on CCh-induced salivary secretion, whereas tolterodine dose-dependently
      decreased it. Ritobegron decreased both the frequency and amplitude of NVC, which
      is similar to its effect on the contractions associated with detrusor
      overactivity (DO) in patients with an overactive bladder (OAB), without affecting
      MP, RV, or CCh-induced salivary secretion. Although tolterodine reduced the
      amplitude of NVC, it also markedly increased RV and significantly inhibited CCh
      induced salivary secretion. These results suggest that use of ritobegron, a beta3
      AR agonist, is unlikely to lead to the residual urine and dry mouth symptoms that
      are associated with anti-muscarinic drugs, and that ritobegron may hold promise
      as a safe and effective agent for OAB treatment.

PMID- 23538509
TI  - Combined pH-impedance monitoring and high-resolution manometry of Japanese
      patients treated with proton-pump inhibitors for persistent symptoms of non
      erosive reflux disease.
AB  - BACKGROUND: Data on acid and non-acid reflux patterns and esophageal function in
      Japanese patients with non-erosive reflux disease (NERD) are limited. The aim of
      this study was to use combined multichannel intraluminal impedance pH monitoring
      (MII-pH) and high-resolution manometry (HRM) to investigate the characteristics
      of Japanese patients who were treated with a "double-dose" (20 mg) of rabeprazol
      (a proton-pump inhibitor; PPI) for persistent symptoms of NERD. METHODS: Twenty
      five patients who complained of typical gastroesophageal reflux disease symptoms,
      which had occurred more than twice a week despite treatment with rabeprazol, were
      enrolled in the study. All patients underwent upper endoscopy, esophageal HRM,
      and 24-h MII-pH monitoring while double-dose PPI therapy was continued. RESULTS:
      Twelve (48.0%) of the patients had a positive symptom index (SI) with 234
      recorded symptoms, 127 (54.3%) of which were related to reflux episodes. Of those
      with reflux episodes, 29 (22.8%) were related to acid reflux, while 98 (77.2%)
      were the result of a weaker acidic reflux. In acid reflux and in mixed (liquid
      gas) reflux, the proximal esophageal region was involved to a significantly
      greater degree (P<0.002 and P=0.005, respectively) than the distal region. In
      liquid reflux, there was no difference between the distal and proximal regions.
      HRM showed that proximal motility parameters were significantly more defective
      than in those of healthy volunteers. CONCLUSIONS: MII-pH monitoring indicated
      that weakly acidic reflux and mixed refluxate in the proximal esophagus is the
      major cause of persistent symptoms in patients with NERD who are being treated
      with PPI. HRM showed that proximal esophageal dysfunction might be a key
      condition that facilitates reflux.

PMID- 23538510
TI  - Surface CD3 expression proceeds through both myosin regulatory light chain 9
      (MYL9)-dependent and MYL9-independent pathways in Jurkat cells.
AB  - CD3 is a complex of polypeptides which form part of the T cell receptor. Normal
      human peripheral pan T cells, express not only CD3, but the mRNA for myosin
      regulatory light chains MYL9, MYL12A, and MYL12B are also significantly
      expressed. In the Jurkat wild strain, an acute T cell leukemia cell line, CD3 on
      the surface and MYL9 mRNA are not expressed, while both MYL12A mRNA and MYL12B
      mRNA are expressed. Jurkat-I, a new clone was established by the transfection of
      the MYL9 gene into the Jurkat wild strain. As a result, the level of CD3
      expressed on the surface of Jurkat-I cells was significantly higher than those in
      the Jurkat wild strain. Phorbol 12-myristate 13-acetate increased the surface CD3
      levels in Jurkat wild strain cells without resulting in MYL9 gene expression,
      indicating that protein kinase C is partially involved in the expression of CD3
      on the surface. These results suggest that surface CD3 expression proceeds
      through both MYL9-dependent and MYL9-independent pathways (i.e. the protein
      kinase C- dependent pathway) in Jurkat cells.

PMID- 23538511
TI  - Enhancing retention and efficacy of cardiosphere-derived cells administered after
      myocardial infarction using a hyaluronan-gelatin hydrogel.
AB  - Cardiosphere-derived cells (CDCs) are under clinical development and are
      currently being tested in a clinical trial enrolling patients who have undergone
      a myocardial infarction. CDCs are presently administered via infusion into the
      infarct-related artery and have been shown in early clinical trials to be
      effective agents of myocardial regeneration. This review describes the
      administration of CDCs in a hyaluronan-gelatin hydrogel via myocardial injection
      and the subsequent improvements in therapeutic benefit seen in animal models.
      Development of a next generation therapy involving the combination of CDCs and
      hydrogel is discussed. 

PMID- 23538513
TI  - Normative functional fitness standards and trends of Portuguese older adults:
      cross-cultural comparisons.
AB  - This cross-sectional study was designed to develop normative functional fitness
      standards for the Portuguese older adults, to analyze age and gender patterns of
      decline, to compare the fitness level of Portuguese older adults with that of
      older adults in other countries, and to evaluate the fitness level of Portuguese
      older adults relative to recently published criterion fitness standards
      associated with maintaining physical independence. A sample of 4,712 independent
      living older adults, age 65-103 yr, was evaluated using the Senior Fitness Test
      battery. Age-group normative fitness scores are reported for the 10th, 25th,
      50th, 75th, and 90th percentiles. Results indicate that both women and men
      experience age-related losses in all components of functional fitness, with their
      rate of decline being greater than that observed in other populations, a trend
      which may cause Portuguese older adults to be at greater risk for loss of
      independence in later years. These newly established normative standards make it
      possible to assess individual fitness level and provide a basis for implementing
      population-wide health strategies to counteract early loss of independence. 

PMID- 23538512
TI  - Prevalence of glaucoma in an urban West African population: the Tema Eye Survey.
AB  - IMPORTANCE: Multiple studies have found an increased prevalence, younger age at
      onset, and more severe course of glaucoma in people of African descent, but these
      findings are based on studies conducted outside Africa. OBJECTIVE: To determine
      the prevalence of glaucoma in an urban West African population of adults. DESIGN
      AND SETTING: A population-based, cross-sectional study of adults 40 years and
      older conducted from September 1, 2006, through December 31, 2008, from 5
      communities in Tema, Ghana. PARTICIPANTS: Participants from randomly selected
      clusters underwent a screening examination that consisted of visual acuity,
      frequency doubling perimetry, applanation tonometry, and optic disc photography.
      Participants who failed any of these tests were referred for complete
      examination, including gonioscopy, standard automated perimetry, and stereoscopic
      optic disc photography. RESULTS: A total of 6806 eligible participants were
      identified, and 5603 (82.3%) were enrolled in the study. The field examination
      referred 1869 participants (33.3%) to the clinic examination, and 1538 (82.2%)
      came for complete examination. A total of 362 participants were identified as
      having glaucoma of any type and category. Primary open-angle glaucoma was the
      underlying diagnosis in 342 participants (94.5%). The prevalence of primary open
      angle glaucoma was 6.8% overall, increasing from 3.7% among those 40 to 49 years
      old to 14.6% among those 80 years and older, and was higher in men than in women
      in all age groups, with an overall male-female prevalence ratio of 1.5. Of the
      participants with glaucoma, 9 (2.5%) were blind using World Health Organization
      criteria, and only 12 (3.3%) were aware that they had glaucoma. CONCLUSIONS AND
      RELEVANCE: The prevalence of glaucoma is higher in this urban West African
      population than in previous studies of people of East or South African and of non
      African descent. Strategies to identify affected persons and effectively manage
      the burden of glaucoma are needed in West Africa.

PMID- 23538514
TI  - Even in pneumococcal sepsis CD62L shedding on granulocytes proves to be a
      reliable functional test for the diagnosis of interleukin-1 receptor-associated
      kinase-4 deficiency.
AB  - A 9-month-old infant presented with fatal pneumococcal sepsis and attenuated
      inflammation indices. Even in septic conditions, flow cytometry-based CD62L
      shedding test on granulocytes proved to be a fast and reliable diagnostic tool
      for the detection of a defect in the innate immunity. Confirmatory immunologic
      and genetic assays identified an autosomal-recessive interleukin-1 receptor
      associated kinase-4 deficiency due to compound heterozygous mutations. 

PMID- 23538515
TI  - Analysis of human metapneumovirus and human bocavirus viral load.
AB  - Viral load (VL) of human metapneumovirus and human bocavirus in infants <12
      months admitted for bronchiolitis was analyzed. VL correlated with length of
      hospital stay in both viruses, human metapneumovirus VL with the duration oxygen
      therapy and human bocavirus VL inversely with days of respiratory effort before
      admission. Infants coinfected by other viruses were younger, but no differences
      were seen regarding VL. 

PMID- 23538516
TI  - Decrease in varicella incidence after implementation of the 2-dose recommendation
      for varicella vaccine in New Hampshire.
AB  - Varicella is a common infectious disease, for which 2-dose vaccination was
      recommended in 2006. Varicella case and vaccination data in New Hampshire were
      analyzed to assess impact of this recommendation on disease incidence and
      clinical characteristics. Varicella incidence decreased after the 2-dose
      recommendation, with greatest reductions in ages 5-19 years. Continued
      vaccination efforts should further reduce disease. 

PMID- 23538517
TI  - Predictors for successful treatment of pediatric deep neck infections using
      antimicrobials alone.
AB  - Among hospitalized children with parapharyngeal or retropharyngeal infection,
      multivariate analysis was performed for the outcomes: successful treatment with
      antibiotics alone, absence of complications and length of stay less than 3 days.
      Those with apparent abscess on computed tomography scan had a lower probability
      of treatment with antimicrobials alone while older age was associated with
      increased probability of treatment with antibiotics alone. 

PMID- 23538518
TI  - Clinical features and genetic analysis of Taiwanese patients with the hyper IgM
      syndrome phenotype.
AB  - OBJECTIVES: Hyper IgM syndrome (HIGM), characterized by recurrent infections, low
      serum IgG and IgA, normal or elevated IgM, defective class switch recombination
      and somatic hypermutation, are heterogeneous disorders with at least 6 distinct
      molecular defects, including the CD40 ligand (CD40L) and the nuclear factor
      kappaB essential modulator (NEMO, also known as IKKgamma) genes (both X-linked),
      the CD40, activation-induced cytidine deaminase (AICDA or AID), uracil-DNA
      glycosylase genes (autosomal recessive) and IkappaBalpha (IKBA) (autosomal
      dominant). Our objective was to determine the molecular basis and clinical
      features of Taiwanese patients with the HIGM phenotype. METHODS: Clinical
      manifestations and candidate genes were analyzed in a nationwide population-based
      study. RESULTS: Among 14 patients (12 unrelated families) since 2003, 10 patents
      were identified (8 families) with CD40L mutations, including 2 novel deletions of
      "A" nucleotide (Del 347A and Del 366A), both frameshift and stop at the 127th
      location; 1 novel AID deletion mutation lack of the 37thAsp and 38th Ser; 1
      ataxia-telangiectasia mutation; and 1 deletion of chromosome 1q42. An adult-onset
      patient with mutant (Thr254Met)CD40L had approximately 30% detectable affinity
      and therefore less severity. Memory B cells decreased in patients with CD40L and
      activation-induced cytidine deaminase mutations. Three mortalities encompassed
      renal cell carcinoma in 1 patient with (Tyr169Asn)CD40L, pneumothorax in 1 with
      (Tyr140Stop)CD40L and pneumonia after chemotherapy in an ataxia-telangiectasia
      patient. One patient without detectable genetic defects but normal lymphocyte
      proliferation resembled the mild form of common variable immune deficiency
      phenotype. CONCLUSIONS: In contrast to those with AICDA mutation, small
      chromosome 1 q42 deletion and unknown genetic defect, the majority (10/14; 71.4%)
      with CD40L mutations except (Thr254Met) and an ataxia-telangiectasia patient had
      the severe form of HIGM phenotype.

PMID- 23538519
TI  - A toddler with acute flaccid paralysis due to West Nile virus infection.
AB  - We report on a 2-year-old boy with acute flaccid paralysis due to West Nile
      neuroinvasive disease. Serum and cerebrospinal fluid serology as well as nerve
      conduction studies were consistent with the diagnosis. He received intravenous
      immunoglobulin and showed gradual improvement and complete recovery of his muscle
      strength, gait and deep tendon reflexes. 

PMID- 23538520
TI  - Respiratory disease and Trichomonas vaginalis in premature newborn twins.
AB  - In premature newborn twins with respiratory disease, Trichomonas vaginalis
      infection was diagnosed by chance findings in respiratory samples and was
      confirmed by polymerase chain reaction of urine and vaginal samples from the boy
      and girl, respectively. Trichomonas vaginalis should be considered as a possible
      cause of respiratory disease in newborns and modern molecular detection
      techniques can help in the diagnosis. 

PMID- 23538521
TI  - Seroprevalence and placental transmission of maternal antibodies specific for
      Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal
      antibodies on the immune response to a primary course of MenACWY-CRM vaccine in
      the United Kingdom.
AB  - BACKGROUND: Maternal antibodies give neonates some protection against bacterial
      infection. We measured antibodies against Neisseria meningitidis serogroups A, C,
      Y and W135 in mothers and their 2-month-old infants at study enrollment. We also
      assessed the impact of maternal antibody present at 2 months of age on the immune
      response to a primary course of quadrivalent meningococcal conjugate vaccine
      (MenACWY-CRM197) given at 2 and 4 months of age. METHODS: This was a single
      center, open-label, randomized study undertaken in Oxford, United Kingdom. Two
      hundred sixteen healthy infants were enrolled in the study and vaccinated with
      MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in
      a subset of infants at 2 months and all infants at 5 months. Antibody and memory
      B-cell responses at 5 months were correlated with maternal antibodies. RESULTS:
      Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides,
      but high serogroup A antibody, whereas 61-78% had protective human complement
      serum bactericidal activity (hSBA) (>=1:4) for serogroups C, W135 and Y but only
      31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA
      >=1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little
      association on responses to MenACWY-CRM197, except a moderate negative
      association between MenC-specific bactericidal antibody at 2 and 5 months (r = 
      0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and
      MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32
      and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after
      vaccination at 2 and 4 months of age. CONCLUSIONS: The levels of serogroup
      specific meningococcal antibodies were low in mothers and 2-month-old infants.
      Immunizing mothers before or during pregnancy with meningococcal conjugate
      vaccines might increase antibody levels in early infancy and provide protection
      against infection due to N. meningitidis.

PMID- 23538522
TI  - Intravenous pentamidine is safe and effective as primary pneumocystis pneumonia
      prophylaxis in children and adolescents undergoing hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a potentially life
      threatening but preventable infection that may occur after hematopoietic stem
      cell transplantation (HSCT). Intravenous pentamidine has been used in the
      prevention of PCP in the post-transplant period, although there are few trials
      published in the literature evaluating its safety and efficacy. METHODS: We
      retrospectively reviewed the medical records of children who underwent HSCT from
      January 1, 2005, to October 1, 2011, who received intravenous pentamidine as
      first-line PCP prophylaxis initiated at admission. Demographic, clinical,
      microbiologic, management and outcome data were collected. RESULTS: One hundred
      sixty-seven consecutive HSCTs in 137 pediatric patients were given intravenous
      pentamidine before myeloablation and then every 28 days until the subject was at
      least a minimum 30 days post-HSCT, had stable neutrophil engraftment (absolute
      neutrophil count >1000/mm for 3 days without growth factor support) and for
      allogeneic patients, no evidence of active graft versus host disease and weaning
      on their immunosuppressive therapy. No cases of PCP were seen in this cohort. Ten
      (7%) had a grade I side effect of nausea/vomiting requiring slower infusion time
      and 2 (2%) had a grade IV reaction with anaphylaxis (rash) and hypotension with 1
      child requiring transfer to the intensive care unit. CONCLUSIONS: Intravenous
      pentamidine was safe and effective for the prevention of PCP in pediatric HSCT
      patients. Given the potential neutropenic effects of trimethoprim
      sulfamethoxazole, compliance with drug administration and inferior efficacy of
      other PCP prophylactic medications, intravenous pentamidine should be considered
      as first-line therapy for the prevention of PCP in children undergoing HSCT.

PMID- 23538523
TI  - Antibody persistence and booster vaccination of a fully liquid hexavalent vaccine
      coadministered with measles/mumps/rubella and varicella vaccines at 15-18 months
      of age in healthy South African infants.
AB  - OBJECTIVE: To assess antibody persistence and booster immunogenicity and safety
      of a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine. METHODS: Phase
      III, open-label, 2-center trial. Infants previously primed at 6, 10, 14 weeks of
      age with DTaP-IPV-Hep B-PRP-T either without (group 1: N = 218) or with hepatitis
      B at birth (group 3: N = 130) or control DTwP-Hib, hepatitis B and oral
      poliovirus vaccine vaccines (group 2: N = 219) received the same vaccine(s) as
      booster (except hepatitis B for group 2) at 15-18 months of age, coadministered
      with measles/mumps/rubella and varicella vaccines (MMR+V). All participants had
      received measles vaccine at 9 months of age. Antibodies were measured prebooster
      and 1 month postbooster vaccination. Safety was evaluated from parental reports.
      Analyses were descriptive. RESULTS: Antibody persistence (seroprotection and
      concentration) at 15-18 months of age was high for each valence and similar in
      each group, except for Hep B (highest in group 3 [extra dose of hepatitis B]) and
      PRP (highest in group 2). Postbooster seroprotection (D, T, IPV, Hep B, PRP) and
      seroconversion (pertussis toxin and filamentous hemagglutinin) rates were high
      and similar in each group (excluding Hep B in group 2 [no booster]); geometric
      mean antibody levels increased markedly in all groups. The response to MMR+V was
      similar in each group. All vaccines were well tolerated. CONCLUSIONS: A booster
      dose of the new DTaP-IPV-Hep B-PRP-T vaccine at 15-18 months of age is highly
      immunogenic and safe compared with licensed comparators, following primary series
      administration in the Expanded Program on Immunization schedule, with or without
      a hepatitis B vaccine at birth and coadministered with MMR+V.

PMID- 23538525
TI  - Changes in infectious disease mortality in children during the past three
      decades.
AB  - BACKGROUND: Our aim was to evaluate changes in infectious disease mortality in
      children in Finland from 1969 to 2004. We especially wanted to find out whether
      infection mortality could be further reduced by means of existing vaccines not
      included in national vaccination program. METHODS: We analyzed infectious disease
      mortality in Finland using data obtained from the official Cause of Death
      statistics for 1969 to 2004. Annual mortality rates were calculated in proportion
      to those at risk of dying. Infection mortality rates were calculated separately
      for neonates and children who were 1 month to 15 years. RESULTS: Childhood
      mortality due to infectious diseases decreased by 89%, from 0.12% in 1969 to
      0.013% in 2004, and neonatal mortality by 69%, from 0.50% to 0.16%. Pneumonia,
      central nervous system infections and septicemia were the most common fatal
      infections in childhood. There were slightly more deaths due to all infections
      and respiratory tract infections in years marked by epidemics of respiratory
      syncytial virus. We estimated that pneumococcal conjugate vaccines would have
      prevented 2 deaths annually in our population, rotavirus vaccines 1 to 2 deaths,
      influenza vaccine 1 death and varicella vaccine 0.7 death. CONCLUSIONS: We found
      that even though mortality from infectious diseases in childhood decreased
      markedly during the period concerned, it could have been further reduced by means
      of existing vaccines. Even though the number of deaths prevented would have been
      small, the number of years of life saved would have been great because the life
      expectancy of children is long.

PMID- 23538524
TI  - Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in
      healthy infants in Japan.
AB  - BACKGROUND: A 13-valent pneumococcal conjugate vaccine (PCV13) containing 6
      additional serotypes not included in the 7-valent PCV has been developed to
      broaden protection against Streptococcus pneumoniae, which is responsible for
      over 500,000 deaths annually worldwide in children <5 years of age. This study in
      Japanese infants evaluated the immunogenicity and safety of PCV13 given
      subcutaneously, the standard route for infant vaccination in Japan. METHODS: This
      phase 3, single-arm, open-label study was conducted at 25 sites. Subjects
      received PCV13 as a 3-dose infant series and a toddler dose. Parents/legal
      guardians recorded local reactions and systemic events after each vaccination.
      The proportion of subjects with serotype-specific antipneumococcal polysaccharide
      immunoglobulin (Ig)G antibody concentrations >=0.35 ug/mL was calculated before
      and 1 month after the infant series and toddler dose. RESULTS: A total of 193
      subjects enrolled. The proportion of subjects achieving pneumococcal IgG antibody
      concentrations >=0.35 ug/mL was >=97.2% for all 13 pneumococcal serotypes 1 month
      after the infant series and 98.9-100% after the toddler dose. IgG geometric mean
      concentrations were 2.57-14.69 ug/mL after the infant series and 2.06-16.33 ug/mL
      after the toddler dose. IgG geometric mean concentrations increased from pre- to
      posttoddler dose by >=2.8-fold, demonstrating a booster effect. Local reactions
      and fever were generally mild or moderate in severity. CONCLUSIONS: PCV13 was
      immunogenic for all serotypes and had a favorable safety profile when
      administered subcutaneously to Japanese infants. PCV13 should offer broader
      serotype protection than 7-valent PCV in preventing pneumococcal disease in
      Japanese children.

PMID- 23538527
TI  - Adolescents with tuberculosis: a review of 145 cases.
AB  - BACKGROUND: Adolescents comprise one-third of pediatric tuberculosis (TB) cases
      in the United States, but there are few specific data on the epidemiology and
      clinical course in this population. METHODS: This was a retrospective review of
      adolescents (12-18 years old) seen at a Children's Tuberculosis Clinic in
      Houston, TX, from 1987 to 2012. RESULTS: One hundred forty-five adolescents were
      identified; median age was 15.4 years: 50% female, 55% were Hispanic, 26% black,
      13% Asian and 1% white; 54 were born abroad. Diagnoses were made after
      symptomatic presentation in 79%, during contact investigations in 14% and after
      screening tuberculin skin testing in the remainder. The most common symptoms were
      fever (63%), cough (60%) and weight loss (30%), but 21% were asymptomatic at
      diagnosis. Only 8% of adolescents with intrathoracic TB had hemoptysis. One
      hundred fourteen (78.6%) had isolated intrathoracic TB, 4 (2.8%) had intra- and
      extrathoracic TB and 27 (18.6%) had extrathoracic TB. The most common sites of
      extrathoracic TB were peripheral lymphadenopathy (10) and meningitis (6). The
      most common radiographic findings were infiltrates (34%), lymphadenopathy (27%),
      cavitary lesions (26%), pleural effusions (19%) and miliary disease (10%). Acid
      fast bacillus smears and mycobacterial cultures were attempted for 97 of 118
      adolescents with intrathoracic and 22 of 27 with extrathoracic disease,
      respectively, resulting in smear/culture positivity in 25% and 54% and 18% and
      45%, respectively. Two patients died, 2 had relapse, 7 had significant sequelae
      and 92% recovered without complication. Seventy three percent of cases
      potentially were preventable. CONCLUSIONS: The clinical, radiologic and
      microbiologic findings in adolescents with TB have features seen in both younger
      children and adults; most cases were preventable.

PMID- 23538526
TI  - Detection of secretory immunoglobulin A in human colostrum as mucosal immune
      response against proteins of the type III secretion system of Salmonella,
      Shigella and enteropathogenic Escherichia coli.
AB  - BACKGROUND: Some enteropathogens use the type III secretion system to secrete
      proteins that allows them to interact with enterocytes and promote bacterial
      attachment or intracellular survival. These proteins are Salmonella invasion
      proteins (Sip), invasion plasmid antigens (Ipa) of Shigella and Escherichia coli
      secreted proteins (Esp) of enteropathogenic E. coli. There are no previous
      studies defining the presence of colostral sIgA against all these 3 major enteric
      pathogens. OBJECTIVE: To evaluate the presence of sIgA in colostrum against
      proteins of the type III secretion system of Salmonella, Shigella and
      enteropathogenic E. coli. METHODS: We collected 76 colostrum samples from
      puerperal women in Lima, Peru. These samples were reacted with type III secretion
      system proteins extracted from bacterial culture supernatants and evaluated by
      Western Blot. RESULTS: Antibodies were detected against Salmonella antigens SipA
      in 75 samples (99%), SipC in 62 (82%) and SipB in 31 (41%); against Shigella
      antigens IpaC in 70 (92%), IpaB in 68 (89%), IpaA in 66 (87%) and IpaD in 41
      (54%); and against enteropathogenic E. coli EspC in 70 (92%), EspB-D in 65 (86%)
      and EspA in 41 (54%). Ten percent of samples had antibodies against all proteins
      evaluated and 42% against all except 1 protein. There was no sample negative to
      all these proteins. CONCLUSIONS: The extraordinarily high frequency of antibodies
      in colostrum of puerperal women detected in this study against these multiple
      enteric pathogens shows evidence of immunological memory and prior exposure to
      these pathogens, in addition to its possible protective role against infection.

PMID- 23538528
TI  - Anion and ion-pair binding by a G-2 poly(ethylene imine) dendrimer.
AB  - The second-generation poly(ethylene imine) dendrimer (L), based on ammonia as the
      initiating core molecule, forms anion and ion-pair complexes in aqueous solution.
      Speciation of the complex species formed and determination of the relevant
      stability constants were performed by means of potentiometric titration in a 0.10
      M NMe4Cl solution at 298.1 K. Protonated forms of L interact with NO3(-), SO4(2
      ), SeO4(2-), HPO4(2-) and H2PO4(-) forming stable 1 : 1 anion complexes. The
      dendritic structure endows the molecule with a greater anion binding ability
      relative to analogous linear polyamines. It was previously reported that L forms
      stable metal complexes. We show here that protonated forms of the mononuclear
      complexes with Cu(2+), Zn(2+) and Cd(2+) bind these anions, and Pb(2+) complexes
      bind NO3(-). The resulting ion-pair complexes show considerable stability thanks
      to the cooperative effect of the oppositely charged partners. Molecular modelling
      calculations show that both anion-ligand and anion-metal ion interactions can
      participate in stabilizing such ion-pair complexes. 

PMID- 23538531
TI  - [The dreams time not over].

PMID- 23538529
TI  - Phosphatidylinositol 4-phosphate 5-kinase alpha negatively regulates nerve growth
      factor-induced neurite outgrowth in PC12 cells.
AB  - Neurite outgrowth, a cell differentiation process involving membrane
      morphological changes, is critical for neuronal network and development. The
      membrane lipid, phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), is a key
      regulator of many important cell surface events of membrane signaling,
      trafficking and dynamics. This lipid is produced mainly by the type I PI 4
      phosphate 5-kinase (PIP5K) family members. In this study, we addressed whether
      PIP5Kalpha, an isoform of PIP5K, could have a role in neurite outgrowth induced
      by nerve growth factor (NGF). For this purpose, we knocked down PIP5Kalpha in
      PC12 rat pheochromocytoma cells by stable expression of PIP5Kalpha microRNA that
      significantly reduced PIP5Kalpha expression and PIP2 level. Interestingly, NGF
      induced neurite outgrowth was more prominent in PIP5Kalpha-knockdown (KD) cells
      than in control cells. Conversely, add-back of PIP5Kalpha into PIP5Kalpha KD
      cells abrogated the effect of NGF on neurite outgrowth. NGF treatment activated
      PI 3-kinase (PI3K)/Akt pathway, which seemed to be associated with reactive
      oxygen species generation. Similar to the changes in neurite outgrowth, the
      PI3K/Akt activation by NGF was potentiated by PIP5Kalpha KD, but was attenuated
      by the reintroduction of PIP5Kalpha. Moreover, exogenously applied PIP2 to
      PIP5Kalpha KD cells also suppressed Akt activation by NGF. Together, our results
      suggest that PIP5Kalpha acts as a negative regulator of NGF-induced neurite
      outgrowth by inhibiting PI3K/Akt signaling pathway in PC12 cells.

PMID- 23538532
TI  - Quality of life of esophagectomized patients: adenocarcinoma versus squamous cell
      carcinoma.
AB  - OBJECTIVE: To evaluate and compare the quality of life (QOL) of patients
      undergoing esophagectomy for treatment of adenocarcinoma of the esophagogastric
      junction and squamous cell carcinoma. METHODS: We conducted a cross-sectional
      study in postoperative patients submitted to esophagectomy for adenocarcinoma of
      the esophagogastric junction (ACA) and squamous cell carcinoma (SCC), using the
      SF-36 questionnaire applied in 24 patients (10 ACAs and 14 SCCs), from the 5th
      months postoperatively, including clinical symptoms and weight change. RESULTS:
      The assessment of QOL showed the best functional capacity (p = 0.018) in the ACA
      group. There was a correlation between the fields "mental health" and "Role of
      Emotions" (p = 0.003) and between "pain" and "physical aspects limitation" (p =
      0.003) in both histological types. Weight loss was greater in ACA (45.9 kg), with
      no significant difference between current BMI (p> 0.66). Dysphagia was reported
      by 83.3% of patients, anorexia by 58.3%, chewing difficulty by 42%, nausea and
      vomiting by 41.7% and diarrhea by 29.2%, with no correlation with QOL reported
      (p> 0.05). CONCLUSION: The highest score for functional capacity indicates that
      ACA patients were able to perform all types of physical activity, including the
      more demanding, at a higher level than patients with SCC. Some symptoms persisted
      postoperatively, but did not affect the quality of life of patients.

PMID- 23538533
TI  - Short-term effect of gastric bypass in obese diabetic patients.
AB  - OBJECTIVE: To study the effect of gastric bypass on blood glucose levels and the
      use of antidiabetic medication in obese patients with diabetes. METHODS: We
      carried out a retrospective cohort study with 44 obese patients with DM2, from
      469 patients undergoing gastric bypass from December 2001 to March 2009. The
      primary endpoints evaluated were fasting glucose and the need for antidiabetic
      medication. RESULTS: The study population consisted of ten (22.7%) men and 34
      (77.3%) women, with a mean age of 45.3 (+/-8.23) years and a body mass index of
      40.9 (+/-5.03) kg/m2. The average time to progression of DM2 was 63.6 (+/-60.9)
      months. Of the 40 patients who used medication to control type 2 diabetes, 20
      (50%) had their medication discontinued at discharge and 13 (32.5%), until nine
      months later. In one patient it was not possible to evaluate the use of
      medication, this being the only exception. Insulin was suspended in ten (100%)
      patients who used it, six (60%) at discharge. Fasting plasma glucose levels
      decreased throughout the study period (p <0.05) when compared with preoperative
      values, and values below 100mg/dl were achieved within seven to nine months.
      CONCLUSION: Obese patients with DM2 undergoing gastric bypass showed improved
      glycemic control and reduced use of hypoglycemic agents in the short-term.

PMID- 23538534
TI  - Impact of the aspirated volume of fat tissue in the insulin resistance after
      liposuction.
AB  - OBJECTIVE: To investigate insulin resistance imposed by liposuction, correlating
      its intensity with the extent of the operation. METHODS: The sample consisted of
      20 female patients without comorbidities, aged between 21 and 43 years, body mass
      index between 19 and 27 kg/m2, undergoing liposuction alone or associated with
      breasts' prosthesis. We assessed insulin resistance at the beginning and end of
      the procedure by calculating the Homeostasis Model Assessment (HOMA-IR). The
      operative variables were length of liposuction, breast prosthesis time, body
      areas submitted to liposuction and total fat aspirated. RESULTS: The liposuction
      time was 94-278 min (mean = 174 min), duration of breast prosthesis 20-140 min
      (mean = 65 min) and total fat aspirated 680-4280 g (mean = 1778 g). Statistical
      analysis was performed by considering a division line of 1500 g of aspirated fat
      and there was a significantly increased insulin resistance by HOMA index greater
      in the group > 1500 g (123% increase) than in the group d" 1500 g (an increase of
      53 %) from the baseline data (p = 0.02). Other operative variables showed no
      significant correlation. CONCLUSION: Insulin resistance shows significant
      increase in liposuction, and it is correlated to the volume of aspirated fat.

PMID- 23538535
TI  - [Laser-assisted lipolysis for gynecomastia: safe and effective skin retraction].
AB  - OBJECTIVES: To evaluate efficacy of laser lipolysis in the treatment of
      gynecomastia to correct breast volume, flaccidity and excess skin without its
      excision. METHODS: Prospectively, 32 patients with gynecomastia under tumescent
      anaesthesia and sedation underwent laser lipolysis with 980 nm diode laser, 15W
      continuous emission and 8 to 12 kJ energy per breast. Externally cold air was
      used to protect the skin. No drainages were used but a compressive bandage.
      Patients evaluated results on a VAS scale. Two doctors evaluated results
      comparing before and 6 month after photographs and also measured the areola and
      chest diameter. RESULTS: Twenty three patients considered results as Very Good, 7
      Good and 2 Fair Cutaneous retraction of the areola was noticeable one month after
      the surgery and was maximum 6 months after. Evaluation by doctors was 26 Very
      Good, 5 Good and 1 Fair. There were no burns, ischemia or lesions in areolas or
      nipples. CONCLUSION: Laser assisted liposuction is a simple and efficacious
      technique, barely traumatic and permits a rapid reincorporation to normal
      activities.

PMID- 23538536
TI  - Laparoscopic totally extraperitoneal inguinal hernia repair: twenty-seven serious
      complications after 4565 consecutive operations.
AB  - OBJECTIVE: To identify and assess the complications of laparoscopic inguinal
      hernia treatment with totally extraperitoneal mesh placement (TEP). METHODS: We
      included patients who had undergone the TEP procedure in a consecutive series of
      4565 laparoscopic hernia repairs between January 2001 and January 2011. Inclusion
      criteria were diagnosis with symptomatic inguinal hernia, including recurrence
      after inguinal hernia repair and previous surgery in the lower abdomen and
      pelvis. All patients were 18 years of age or above. Patients with incarcerated
      hernia in emergency were excluded from the study. RESULTS: A total of 4565
      hernias were included in the study. In the group, there were 27 severe
      complications (0.6%): 12 bleedings (0.25%), two bladder lesions (0.04%), five
      intestinal obstructions (0.11%), four intestinal perforations (0.09%) one injury
      to the iliac vein (0.02%), one femoral nerve injury (0.02%), two lesions of vas
      deferens (0.04%) and two deaths (0.02%) (pulmonary embolism, peritonitis).
      CONCLUSION: The rate of complications with the TEP procedure is low. Laparoscopic
      hernia repair technique is reproducible and reliable. In our experience, there
      are contraindications to the TEP procedure. TEP technique must be meticulous to
      avoid intraoperative complications (bipolar diathermy). Complications can occur
      even after the surgeon has gained substantial experience.

PMID- 23538537
TI  - Local complications after industrial liquid silicone injection: case series.
AB  - OBJECTIVE: To analyze a case series of patients who underwent injection of
      industrial liquid silicone in a clandestine manner and by unauthorized persons.
      METHODS: We conducted a retrospective analysis of medical records of patients
      treated between September 2003 and December 2010. Data regarding gender, age,
      location and volume of silicone injected, time between application and clinical
      manifestations, complications, treatment and outcome were collected. Early
      manifestations were defined as occurring within 30 days of injection and late
      manifestations, the ones arising after this period. RESULTS: We treated 12
      patients, eight were male, seven transsexuals. The volume injected ranged from 5
      ml to 2000 ml, being unknown in three cases. The most often used injected sites
      were the thighs and buttocks. Eight patients had early manifestations, with
      inflammation and/or infection. Surgical debridement was necessary in five cases.
      Three patients with a history of injection in the breast region underwent
      adenomastectomy. There was one death due to refractory septic shock. CONCLUSION:
      The use of industrial liquid silicone should be completely contraindicated as a
      filling material and modification of body contouring, and may have serious
      complications, even death.

PMID- 23538538
TI  - Macro and microscopic analysis of island skin grafts after low-level laser
      therapy.
AB  - OBJECTIVE: To observe the effects of low intensity laser therapy in inflammation,
      wound healing and epithelialization of island skin grafts. METHODS: Twenty rats
      were subjected to this grafting technique and divided subsequently into two equal
      groups, one treated with laser and the other control. RESULTS: there was less
      inflammation, faster healing, epithelialization and keratinization in the laser
      treated animals when compared to the untreated. CONCLUSION: Low intensity laser
      therapy is helpful to island skin grafting.

PMID- 23538539
TI  - L-arginine action in cutaneous flap evolution under nicotine exposure in rats.
AB  - OBJECTIVE: To evaluate whether treatment with L-arginine influences the healing
      of skin flaps in rats exposed to nicotine. METHODS: 40 male Wistar rats weighing
      142.4 +/- 10.1 g were separated into four groups: GC: treatment with 7.4 pH
      phosphate buffer, submitted to skin flap and observation for ten days; GN:
      exposure to nicotine for four weeks, submitted to skin flap and observation for
      ten days; GA: treatment with 7.4 pH phosphate buffer for four weeks, submitted to
      skin flap and arginine treatment for ten days; GAN: exposure to nicotine for four
      weeks, submitted to skin flap and treatment with arginine for ten days. We
      evaluated: areas of necrosis, re-epithelialization, inflammatory reaction and
      formation of granulation tissue by HE stain; the total area of deposition and
      differentiation of collagens I and III by histometry with picrosirius staining;
      and the scar vascular density by immunohistochemical staining with monoclonal
      anti-CD34 antibodies. RESULTS: The percentages of necrotic areas in GN and GNA
      were higher (p <0.001) than in GC and GA. In histological scores, collagen
      deposition, and the percentage of type I collagen, GA and GC were similar to each
      other (p> 0.05), but higher (p <0.001) than GA and GNA; as for vascular
      densities, they were lower in GN and GAN (p <0.001) than in GC and GA.
      CONCLUSION: Exposure to nicotine inhibited the effects of arginine and in
      unexposed mice there was induction of angiogenesis and improvement in the total
      collagen deposition in the skin flaps.

PMID- 23538540
TI  - Ischemic preconditioning in different times and its effect on bacterial
      translocation induced by intestinal ischemia and reperfusion in rats.
AB  - OBJECTIVE: To evaluate the effects of different times of ischemic preconditioning
      (IPC) on intestinal bacterial translocation (BT). METHODS: Thirty Wistar rats
      weighing 280 +/- 27 g were divided into five groups. In the IR group (n = 6),
      laparotomy was performed and the superior mesenteric artery was occluded by an
      atraumatic microclamp for 30 minutes. In the four preconditioning groups (n = 6
      each) before the 30 minutes of ischemia-reperfusion (I/R) rats underwent IPC for
      two, five, ten and 15 minutes, followed by the same time of reperfusion. In order
      to assess whether the time of preconditioning influenced the onset of bacterial
      translocation, samples of mesenteric lymph nodes, liver and spleen were collected
      in sterile conditions twenty-four hours after the procedures for quantification
      of bacterial colony forming units per gram of tissue (CFU/g). Blood was collected
      for measurement of cytokines. RESULTS: In the I/R group, the total CFU/g in
      mesenteric lymph nodes, spleen, liver, as well as the serum TNF-a, IL-1a and IL-6
      were significantly higher than in the other groups (p <0.05). Preconditioning for
      15 minutes significantly attenuated BT and serum cytokines when compared to other
      periods of preconditioning (p <0.05). CONCLUSION: Our data suggest
      preconditioning as a key factor to reduce bacterial translocation in intestinal
      I/R. On a scale of two to 15 minutes, the best time of ischemic preconditioning
      for the attenuation of bacterial translocation was 15 minutes.

PMID- 23538541
TI  - Verification of the feasibility of autogenous testis implant in omentum and
      abdominal wall in mice.
AB  - OBJECTIVE: To verify the feasibility of autologous transplantation of testes to
      the abdominal wall and omentum of rats without vascular anastomosis, analyzing
      the histological structure of the testicular cells after implantation. METHODS:
      We used 60 male Wistar rats, 10-12 weeks of age, which were divided into three
      groups: control group: 20 rats without orchiectomy with sham operation; group 2:
      20 rats undergoing bilateral orchiectomy, with one of the testicles being
      implanted into the greater omentum; and group 3: 20 rats submitted to bilateral
      orchiectomy, with one testicle implanted in the abdominal wall. After two months
      they were euthanized and the testes evaluated by histopathology. RESULTS: the
      weight of the implants had a loss of 0.62 g in group 2, 0.73 g in group 3, whilst
      in the control group testes increased by 0.1 g. In pathological studies, the
      testicular structure was preserved in the control group; in group 2 there was 80%
      of inflammation and necrosis, Sertoli and Leydig cells were not visualized, and
      seminiferous tubules were found in two animals; in group 3 we found 75% of
      inflammation and a 60% necrosis, Sertoli cells could be visualized in only one
      specimen, while Leydig cells were seen in three. CONCLUSION: autologous
      transplantation of testis to the greater omentum and abdominal wall without
      vascular anastomosis is not viable in rats.

PMID- 23538542
TI  - [Topical haemostatic agents and tissue adhesives].
AB  - In the last ten years the hemostatic agents and tissue adhesives have been
      frequently used and they are positive alternatives to prevent excessive blood
      loss. The objective of this review is to discuss the characteristics of each of
      these agents to facilitate the surgeon's decision when choosing the most suitable
      product for every type of bleeding and nature of hemorrhage. A survey of the
      literature on the subject, in English and in Portuguese, was conducted using
      PubMed (www.pubmed.com) and Google (www.google.com.br) to find recent articles on
      the topic. Based on these studies, the authors conducted a didactic review on the
      hemostatic agents and tissue adhesives and concluded that there is a hemostatic
      agent to be used in each specific scenario.

PMID- 23538543
TI  - [Diverticulopexy for the treatment of Zenker's diverticulum].
AB  - Zenker's diverticulum is a pseudodiverticulum through a muscular defect in the
      posterior pharyngeal wall at the area between the inferior pharyngeal constrictor
      muscles of the pharynx and the cricopharyngeus muscle. Although endoscopic
      techniques have made significant progress, the surgical treatment remains the
      gold standard. There are two main techniques: diverticulectomy (resection of the
      diverticulum) and diverticulopexy. The main advantages of diverticulopexy are
      mostly linked to the absence of an esophageal anatomosis and its possible
      complications: cervical fistulae, mediastinitis, esophageal stenosis and wound
      infection, which allows a rapid recover with satisfactory oral intake. The
      purpose of this article is to describe in details the technique for
      diverticulopexy to the prevertebral ligament in association with a miotomy of the
      cricopharyngeus muscle.

PMID- 23538544
TI  - [Analysis of anatomical pieces preservation with polyester resin for human
      anatomy study].
AB  - OBJECTIVE: To evaluate the use of polyester resin in preserving anatomical
      specimens for the study of human anatomy. METHODS: We used 150 anatomical
      specimens, comprised of unfixed (fresh), fixed in 10% formalin and vascular casts
      of organs injected with vinyl acetate and polyester resin. The solution used
      consisted of polyester resin with the diluent styrene monomer and catalyst
      (peroxol). After embedding in this solution, models in transparent resin were
      obtained, allowing full observation of structures and conservation of the
      specimens used. RESULTS: upon evaluation of the specimens, we observed a high
      degree of transparency, which promoted a complete visualization of structures
      with perfect preservation of the anatomy. The average time for the completion of
      the embedding was 48 hours. Only 14 specimens (9.3%) were lost during the
      preparation. CONCLUSION: Polyester resin can be used for preserving anatomical
      specimens for teaching human anatomy in a practical, aesthetic and durable way.

PMID- 23538545
TI  - [Plummer-Vinson syndrome: a case report].
AB  - We present a case of Plummer-Vinson syndrome, which is a rare condition nowadays.
      The diagnosis was made after years of the disease, many doctors having attended
      the patient. The treatment consisted of oral supplementation of iron and
      endoscopic dilatations. The patient is asymptomatic.

PMID- 23538546
TI  - [Boerhaave's syndrome: case report].
AB  - Spontaneous esophageal rupture carries high morbidity and mortality. The main
      prognostic factor is early diagnosis, before 12 hours, and appropriate treatment.
      This is a case report of a 41-years-old man with late esophageal rupture
      diagnosis treated successfully with transmediatinal esophagectomy and esophageal
      gastric tube cervical anastomosis.

PMID- 23538547
TI  - Sequential closure of the abdominal wall with continuous fascia traction (using
      mesh or suture) and negative pressure therapy.
AB  - The last decade was marked by a multiplication in the number of publications on
      (and usage of) the concept of damage control laparotomy, resulting in a growing
      number of patients left with an open abdomen (or peritoneostomy). Gigantic
      hernias are among the dreaded consequences of damage control and the
      impossibility of closing the abdomen during the initial hospital admission. To
      minimize this sequela, the literature has proposed many different strategies. In
      order to explore this topic, the "Evidence-based Telemedicine - Trauma & Acute
      Care Surgery" (EBT -TACS) conducted a literature review and critically appraised
      the most relevant articles on the topic. No commercially available systems for
      the closure of peritoneostomies were analyzed, except for negative pressure
      therapy. Three relevant and recently published studies on the sequential closure
      of the abdominal wall (with mesh or sutures) plus negative pressure therapy were
      appraised. For this appraisal 2 retrospective and one prospective study were
      included. The EBT-TACS meeting was attended by representatives of 6 Universities
      and following recommendations were generated: (1) the association of negative
      pressure therapy and continuous fascia traction with mesh or suture and adjusted
      periodically appears to be a viable surgical strategy to treat peritoneostomies.
      (2) the primary dynamic abdominal closure with sutures or mesh appears to be more
      efficient and economically sound than leaving the patient with a gigantic hernia
      to undergo complex repair at a later date. New studies including larger number of
      patients classified according to their different presentations and diseases are
      needed to better define the best surgical treatment for patients with
      peritoneostomies.

PMID- 23538549
TI  - Electrocardiographic features of patients with earthquake related posttraumatic
      stress disorder.
AB  - AIM: To analyze electrocardiographic features of patients diagnosed with
      posttraumatic stress disorder (PTSD) after the Van-Ercis earthquake, with a shock
      measuring 7.2 on the Richter scale that took place in Turkey in October 2011.
      METHODS: Surface electrocardiograms of 12 patients with PTSD admitted to Van
      Ercis State Hospital (Van, Turkey) from February 2012 to May 2012 were examined.
      Psychiatric interviews of the sex and age matched control subjects, who had
      experienced the earthquake, confirmed the absence of any known diagnosable
      psychiatric conditions in the control group. RESULTS: A wide range of
      electrocardiogram (ECG) parameters, such as P-wave dispersion, QT dispersion, QT
      interval, Tpeak to Tend interval, intrinsicoid deflection durations and other
      traditional parameters were similar in both groups. There was no one with an
      abnormal P wave axis, short or long PR interval, long or short QT interval,
      negative T wave in lateral leads, abnormal T wave axis, abnormal left or right
      intrinsicoid deflection duration, low voltage, left bundle branch block, right
      bundle branch block, left posterior hemiblock, left or right axis deviation, left
      ventricular hypertrophy, right or left atrial enlargement and pathological q(Q)
      wave in either group. CONCLUSION: The study showed no direct effect of earthquake
      related PTSD on surface ECG in young patients. So, we propose that PTSD has no
      direct effect on surface ECG but may cause electrocardiographic changes
      indirectly by triggering atherosclerosis and/or contributing to the ongoing
      atherosclerotic process.

PMID- 23538550
TI  - Changes in nucleosome position at transcriptional start sites of specific genes
      in Zea mays mediator of paramutation1 mutants.
AB  - Nucleosomes facilitate compaction of DNA within the confines of the eukaryotic
      nucleus. This packaging of DNA and histone proteins must accommodate cellular
      processes, such as transcription and DNA replication. The repositioning of
      nucleosomes to facilitate cellular processes is likely regulated by several
      factors. In Zea mays, Mediator of paramutation1 (MOP1) has been demonstrated to
      be an epigenetic regulator of gene expression. Based on sequence orthology and
      mutant phenotypes, MOP1 is likely to function in an RNA-dependent pathway to
      mediate changes to chromatin. High-resolution microarrays were used to assay the
      distribution of nucleosomes across the transcription start sites (TSSs) of ~400
      maize genes in wild type and mutant mop1-1 tissues. Analysis of nucleosome
      distribution in leaf, immature tassel and ear shoot tissues resulted in the
      identification of three genes showing consistent differences in nucleosome
      positioning and occupancy between wild type and mutant mop1-1. These specific
      changes in nucleosome distribution were located upstream as well as downstream of
      the TSS. No direct relationship between the specific changes in nucleosome
      distribution and transcription were observed through quantitative expression
      analysis in these tissues. In silico prediction suggests that nucleosome
      positioning is not dictated by intrinsic DNA sequence signals in the TSSs of two
      of the identified genes, suggesting a role for chromatin remodeling proteins in
      MOP1-mediated pathways. These results also indicate that MOP1 contributions to
      nucleosome position may be either separate from changes in gene expression, or
      cooperative with development and other levels of regulation in coordinating gene
      expression. 

PMID- 23538551
TI  - Eyes on DNA methylation: current evidence for DNA methylation in ocular
      development and disease.
AB  - Epigenetic modulation of chromatin states constitutes a vital component of the
      cellular repertoire of transcriptional regulatory mechanisms. The development of
      new technologies capable of generating genome-wide maps of chromatin
      modifications has re-energized the field. We are now poised to determine how
      species- and tissue-specific patterns of DNA methylation, in concert with other
      chromatin modifications, function to establish and maintain cell- and tissue
      specific patterns of gene expression during normal development, cellular
      differentiation, and disease. This review addresses our current understanding of
      the major mechanisms and function of DNA methylation in vertebrates with a
      historical perspective and an emphasis on what is known about DNA methylation in
      eye development and disease.

PMID- 23538552
TI  - Single port laparoscopic right hemicolectomy for ileocolic intussusception.
AB  - A 36-year-old male was admitted with right lower abdominal pain and diarrhea for
      more than 3 mo. Colonoscopy and a barium enema study revealed a submucosal tumor
      over the cecum, but computed tomography showed an ileal lipoma. There was no
      definitive diagnosis preoperatively, but ileocolic intussusception was noted
      during surgery. Single port laparoscopic radical right hemicolectomy was
      performed because intra-operative reduction failed. The histological diagnosis of
      the resected tumor was lipoma. Single port laparoscopic surgery has recently been
      proven to be safe and feasible. There are advantages compared with conventional
      laparoscopic surgery, such as smaller incision wounds, fewer port site
      complications, and easier conversion. However, there are some drawbacks which
      need to be overcome, such as difficulties in triangulation and instrument
      clashing. If there are no contraindications to laparoscopy, single port
      laparoscopic surgery can be performed safely and should be considered for
      diagnosis and treatment of intussusception in adults. Here, we report the first
      case of ileocolic intussusception successfully treated by single port
      laparoscopic surgery.

PMID- 23538554
TI  - Failure of systemic propranolol therapy for choroidal hemangioma of Sturge-Weber
      syndrome: a report of 2 cases.

PMID- 23538553
TI  - Efficacy of the vaccination in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is associated with conditions that may
      predispose to infections, such as the lack of an appropriate innate immune
      response to infectious agents, malnutrition, surgery, and immunosuppressive and
      biological drugs. Some of these infections may be preventable by vaccination.
      Therefore, for this particular patient population, the benefits of implementing a
      well-established immunization protocol in daily clinical practice are potentially
      even greater than for the general population. In recent years international
      consensus guidelines have been published, but in spite of theses recommendations,
      studies have shown that a significant number of patients with IBD remain
      inadequately immunized. Another important issue regarding immunization in this
      population is that vaccine efficacy among patients receiving immunosuppressive
      therapies has been variable. In a healthy population, a humoral immune response
      to hepatitis B vaccination (HBV) is expected in > 90%, whereas a much lower rate
      is achieved in the IBD patients. Immunosuppressive, anti-tumor necrosis factor
      therapy and disease activity have been implicated in the impaired efficacy of the
      vaccination. The serological response to HBV should be confirmed and patients
      with an inadequate response should receive a second full series of vaccine.
      Modified dosing regimens, including doubling the standard antigen dose, might
      increase the effectiveness. Response to influenza, pneumococcal and tetanus
      immunization is still not clear, as there are studies that show a normal response
      to the vaccination while others demonstrate a lack of efficacy. We pose a series
      of questions on the efficacy of the different vaccinations recommended for IBD
      patients and attempt to answer them using scientific evidence.

PMID- 23538555
TI  - Personality factors predict spicy food liking and intake.
AB  - A number of factors likely affect the liking of capsaicin-containing foods such
      as social influences, repeated exposure to capsaicin, physiological differences
      in chemosensation, and personality. For example, it is well known that repeated
      exposure to capsaicin and chilies can result in chronic desensitization. Here, we
      explore the relationship between multiple personality variables - body
      awareness/consciousness, sensation seeking, and sensitivity to punishment, and
      sensitivity to reward - and the liking and consumption of capsaicin-containing
      foods. As expected, a strong relationship was found between liking of spicy foods
      and frequency of chili consumption. However, no association was observed between
      frequency of chili consumption and the perceived burn/sting of sampled capsaicin.
      Nor was there any association between perceived burn/sting of capsaicin and any
      of the personality measures. Private Body Consciousness did not relate to any of
      the measures used in the current study. Sensation Seeking showed positive
      correlations with the liking of spicy foods, but not non-spicy control foods.
      Sensitivity to Punishment showed no relation with frequency of chili consumption,
      and nonsignificant negative trends with liking of spicy foods. Conversely,
      Sensitivity to Reward was weakly though significantly correlated with the liking
      of a spicy meal, and similar nonsignificant trends were seen for other spicy
      foods. Frequency of chili consumption was positively associated with Sensation
      Seeking and Sensitivity to Reward. Present data indicate individuals who enjoy
      spicy foods exhibit higher Sensation Seeking and Sensitivity to Reward traits.
      Rather than merely showing reduced response to the irritating qualities of
      capsaicin as might be expected under the chronic desensitization hypothesis,
      these findings support the hypothesis that personality differences may drive
      differences in spicy food liking and intake.

PMID- 23538556
TI  - Breast Arterial Calcification: a New Marker of Cardiovascular Risk?
AB  - Mammographically-detected breast arterial calcifications (BAC) are considered to
      be an incidental finding without clinical importance since they are not
      associated with increased risk of breast cancer. The goal of this article is to
      review existing evidence that the presence of BAC on mammography correlates with
      several (but not all) traditional cardiovascular disease (CVD) risk factors and
      with prevalent and incident CVD. Thus, BAC detected during routine mammography is
      a noteworthy finding that could be valuable in identifying asymptomatic women at
      increased future CVD risk that may be candidates for more aggressive management.
      In addition, there are notable differences in measures of subclinical
      atherosclerosis burden in women (ie, coronary artery calcification) by
      race/ethnic background, and the same appears to be true for BAC, although data
      are very limited. Another noteworthy limitation of prior research on BAC is the
      reliance on absence vs presence of BAC; no study to date has determined gradation
      of BAC. Further research is thus required to elucidate the role of BAC gradation
      in the prediction of CVD outcomes and to determine whether adding BAC gradation
      to prediction models based on traditional risk factors improves classification of
      CVD risk.

PMID- 23538557
TI  - Passive and Active Approach Responses in Preference Assessment for Children With
      Profound Multiple Disabilities and Minimal Movement.
AB  - We assessed the activity preferences of three children with profound multiple
      disabilities and minimal movement using a single stimulus presentation procedure.
      We recorded active approach, passive approach, and rejection responses on each
      trial during the assessments. Active approach included reaching for, touching, or
      manipulating the stimulus. Passive approach included looking at or orienting
      toward the stimulus and happiness indicators such as smiling. Active approaches
      and rejection responses were infrequent, but preference hierarchies based on
      passive approaches emerged for all three children. Two children were available
      for reinforcer testing after the preference assessments. The identified high
      preference activities based on passive approach responses maintained higher rates
      of switch pressing than the low preference activities for one child and
      maintained approximately the same rates of switch pressing for the second child.

PMID- 23538558
TI  - Search for inhibitors of endocytosis: Intended specificity and unintended
      consequences.
AB  - We discuss here the variety of approaches that have been taken to inhibit
      different forms of endocytosis. Typically, both non-specific and specific
      chemical inhibitors of endocytosis are tried in order to "classify" entry of a
      new plasma membrane protein into one of the various types of endocytosis. This
      classification can be confirmed through genetic approaches of protein depletion
      or overexpression of mutants of known endocytosis machinery components. Although
      some new compounds have been designed to be selective in biochemical assays, we
      caution investigators to be alert to the unintended consequences that sometimes
      arise when these compounds are applied to intact cells.

PMID- 23538559
TI  - Sense of coherence: effect on adherence and response to resistance training in
      older people with hip fracture history.
AB  - Our aim was to study the effects of sense of coherence (SOC) on training
      adherence and interindividual changes in muscle strength, mobility, and balance
      after resistance training in older people with hip fracture history. These are
      secondary analyses of a 12-week randomized controlled trial of progressive
      resistance training in 60- to 85-year-old community-dwelling people 0.5-7 years
      after hip fracture (n = 45; ISRCTN34271567). Pre- and posttrial assessments
      included SOC, knee extension strength, walking speed, timed up-and-go (TUG), and
      Berg Balance Scale (BBS). Group-by-SOC interaction effects (repeated-measures
      ANOVA) were statistically significant for TUG (p = .005) and BBS (p = .040), but
      not for knee extension strength or walking speed. Weaker SOC was associated with
      poorer training adherence (mixed model; p = .009). Thus, more complicated
      physical tasks did not improve in those with weaker SOC, independently of
      training adherence. Older people with weaker SOC may need additional psychosocial
      support in physical rehabilitation programs to optimize training response. 

PMID- 23538560
TI  - Contribution of the production of quormones to some phenotypic characteristics of
      Pseudomonas aeruginosa clinical strains.
AB  - The contribution of quorum sensing in some phenotypic and pathogenic
      characteristics of Pseudomonas aeruginosa was studied. The production of
      acylhomoserine lactones (AHL) by planktonic cultures of eight clinical and
      reference strains of P. aeruginosa was evaluated using two biosensors. The
      adhesion of the bacteria on a surface (Biofilm Ring Test (r), BFRT), their
      capacity to develop a biofilm (crystal violet staining method, CVSM), their
      sensitivity to tobramycin and their secretion of proteases or of rhamnolipids
      were also measured. The production and the release of AHL widely varied among the
      eight strains. An analysis of the extracts by TLC showed that 3-oxo-C8-HSL, 3-oxo
      C10-HSL and 3-oxo-C12-HSL were released by the five strains producing the highest
      amount of Cn>=6-HSL. The genes lasI and lasR involved in the synthesis and
      response to 3-oxo-C12-HSL were detected in the genomes of all strains. Two
      clinical strains had deletions in the lasR gene leading to truncation of the
      protein. One subpopulation of the PAO1 strain had a major deletion (98 bp) of the
      lasR gene. Strains with significant mutations of lasR secreted the lowest amount
      of AHL, probably due to deficiencies in the self-induction and amplification of
      the synthesis of the lactone. These strains formed a biofilm with low biomass. C4
      HSL production also differed among the strains and was correlated with
      rhamnolipid production and biofilm formation. Whereas the production of AHL
      varied among P. aeruginosa strains, few correlations were observed with their
      phenotypic properties except with their ability to form a biofilm.

PMID- 23538561
TI  - Activity of antimalarial drugs in vitro and in a murine model of cutaneous
      leishmaniasis.
AB  - The currently used treatments for leishmaniasis, a neglected parasitic disease,
      are associated with several side effects, high cost and resistance of the
      Leishmania parasites. Here we evaluated in vitro and in vivo the antileishmanial
      activity of five antimalarial drugs against Leishmania amazonensis. Mefloquine
      was effective against promastigotes in axenic cultures and showed an IC50
      (concentration giving half-maximal inhibition) value of 8.4+/-0.7 uM. In
      addition, mefloquine, chloroquine and hydroxychloroquine were active against
      intracellular amastigotes in macrophage-infected cultures, presenting IC50 values
      of 1.56+/-0.19 uM, 0.78+/-0.08 uM and 0.67+/-0.12 uM, respectively. The
      ultrastructural analysis of chloroquine- or mefloquine-treated amastigotes showed
      an accumulation of multivesicular bodies in the cytoplasm of the parasite,
      suggesting endocytic pathway impairment, in addition to the formation of myelin
      like figures and enlargement of the Golgi cisternae. CBA mice were infected with
      L. amazonensis in the ear dermis, and treated by oral and/or topical routes with
      chloroquine and mefloquine. Treatment of L. amazonensis-infected mice with
      chloroquine by the oral route reduced lesion size, which was associated with a
      decrease in the number of parasites in the ear, as well as the parasite burden in
      the draining lymph nodes. In contrast, mefloquine administration by both routes
      decreased the lesion size in infected mice without causing a reduction in
      parasite burden. Our results revealed a promising antileishmanial effect of
      chloroquine and suggest its use in cutaneous leishmaniasis treatment.

PMID- 23538562
TI  - A case of pulmonary aspergilloma without actinomycosis.

PMID- 23538563
TI  - Comparison of four laboratory methods in the detection of carbapenemase-producing
      Enterobacteriaceae.

PMID- 23538564
TI  - alpha-Cyclodextrin decreases cholera toxin binding to GM1-gangliosides.
AB  - Cholera toxin (CT), the principal virulence factor secreted by Vibrio cholerae,
      is an A-B5 type exotoxin that binds to host cell GM1-gangliosides and is
      responsible for cholera diarrhoea. We tested the hypothesis that the cyclic
      hexasaccharide alpha-cyclodextrin (alpha-CD), but not the cyclic heptasaccharides
      methyl-beta-cyclodextrin (MD-beta-CD) and hydroxypropyl-beta-cyclodextrin (HP
      beta-CD) inhibit binding of CT to GM1-gangliosides. We report that alpha-CD
      decreases CT binding to GM1-ganglioside-coated microtitre plate wells and on the
      surface of fixed HeLa cells in a concentration-dependent manner, suggesting that
      this may be a promising lead for the development of compounds with therapeutic
      properties.

PMID- 23538565
TI  - Community spread of extended-spectrum beta-lactamase-producing Escherichia coli,
      Klebsiella pneumoniae and Proteus mirabilis: a long-term study in Japan.
AB  - Community-acquired infections caused by extended-spectrum beta-lactamase (ESBL)
      producing bacteria, particularly CTX-M-producing Escherichia coli, are a rising
      concern worldwide. There are few data from Japan on the acquisition of ESBLs in
      the community or the influx of these bacteria into hospitals. Therefore, we
      examined the prevalence of ESBL carriage in outpatients, in order to estimate the
      spread of ESBLs in community settings. We analysed bacterial isolates from
      outpatient samples at our institution over a 9-year period from 2003 to 2011,
      with respect to epidemiological data on ESBL-producing bacteria and their
      genotypic features. Out of 5137 isolates, 321 (6.3 %) were ESBL producers,
      including E. coli, Klebsiella pneumoniae and Proteus mirabilis. The detection
      rates of the ESBL-producing isolates gradually increased and reached 14.3, 8.7
      and 19.6 % for E. coli, K. pneumoniae and P. mirabilis strains, respectively, in
      2011. Genotyping analysis showed that many of the strains produced multiple beta
      lactamases, including TEM, SHV and CTX-M, rather than just CTX-M. The CTX-M-9
      group was dominant among the CTX-M genotypes; further, the CTX-M-1 and M-2 groups
      were also detected (~30 %). This is believed to be the first report from Japan
      showing a definite increase in ESBL detection in outpatients. In addition, our
      findings suggest the simultaneous community spread of diverse ESBL genotypes, not
      an expansion of particular ESBL genes.

PMID- 23538566
TI  - Cognitive performance on the mini-mental state examination and the montreal
      cognitive assessment across the healthy adult lifespan.
AB  - OBJECTIVE: We sought to compare age-related performance on the Mini-Mental State
      Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) across the adult
      lifespan in an asymptomatic, presumably normal, sample. BACKGROUND: The MMSE is
      the most commonly used brief cognitive screening test; however, the MoCA may be
      better at detecting early cognitive dysfunction. METHODS: We gave the MMSE and
      MoCA to 254 community-dwelling participants ranging in age from 20 to 89,
      stratified by decade, and we compared their scores using the Wilcoxon signed rank
      test. RESULTS: For the total sample, the MMSE and MoCA differed significantly in
      total scores as well as in visuospatial, language, and memory domains (for all of
      these scores, P<0.001). Mean MMSE scores declined only modestly across the
      decades; mean MoCA scores declined more dramatically. There were no consistent
      domain differences between the MMSE and MoCA during the third and fourth decades;
      however, significant differences in memory (P<0.05) and language (P<0.001)
      emerged in the fifth through ninth decades. CONCLUSIONS: We conclude that the
      MoCA may be a better detector of age-related decrements in cognitive performance
      than the MMSE, as shown in this community-dwelling adult population.

PMID- 23538567
TI  - Influence of educational status on executive function and functional balance in
      individuals with Parkinson disease.
AB  - OBJECTIVE: This study investigated whether educational status influenced how
      people with Parkinson disease (PD) performed on Parts A, B, and DELTA of the
      Trail Making Test (TMT) and on the Berg Balance Scale (BBS). BACKGROUND: Recent
      studies have shown that educational status may influence cognitive and motor test
      performance. METHODS: We gave the TMT and the BBS to assess executive function
      and functional balance in 28 people with PD (Hoehn and Yahr score between 2 and
      3) and 30 healthy elderly people. Participants reported their number of years of
      formal education. We divided each group of participants by educational status:
      low (4 to 10 years of education) or high (>=11 years). RESULTS: In both the PD
      (P=0.018) and control (P=0.003) groups, participants with low educational status
      performed worse on the TMT Part B than did those with high educational status.
      Within the PD group, the less-educated participants scored worse on the BBS than
      did the more educated (P<0.001); this difference was not significant between the
      more- and less-educated controls (P=0.976). CONCLUSIONS: Whether or not they had
      PD, less-educated people performed worse than more-educated people on the TMT
      Part B. Educational status affected executive function, but PD status did not.
      Among individuals with PD, educational status influenced functional balance.

PMID- 23538568
TI  - Executive function in nephropathic cystinosis.
AB  - OBJECTIVE: We studied executive function (EF) in children and adolescents with
      cystinosis. BACKGROUND: Cystinosis is a genetic metabolic disorder in which the
      amino acid cystine accumulates in all organs of the body, including the brain.
      Previous research has shown that individuals with cystinosis have visuospatial
      deficits, but normal intelligence and intact verbal abilities. Better
      understanding of the behavioral phenotype associated with cystinosis could have
      important implications for treatment. METHODS: Twenty-eight children with
      cystinosis and 24 control participants (age range 8 to 17 years) underwent
      selected Delis-Kaplan executive function system tests for neuropsychological
      assessment of EF, and the participants' parents completed the behavior rating
      inventory of executive function. RESULTS: Participants with cystinosis performed
      significantly more poorly than controls on all Delis-Kaplan Executive Function
      System indices examined and on the behavior rating inventory of executive
      function metacognition index and global executive composite. CONCLUSIONS: EF is
      an area of potential risk in cystinosis. Our data have implications not only for
      the function of affected children and adolescents in school and daily life, but
      also for disease management and treatment adherence. Our findings can aid in the
      design and implementation of interventions and lead to a greater understanding of
      brain-behavior relationships in cystinosis.

PMID- 23538570
TI  - Isolated and persistent cognitive dysfunction in a patient with acute
      disseminated encephalomyelitis.
AB  - We report a case of pathology-proven acute disseminated encephalomyelitis (ADEM)
      in which the patient's symptoms were solely cognitive. Although cognitive
      dysfunction is a well-recognized symptom in adults with multiple sclerosis,
      cognitive assessment of adults with ADEM has rarely been reported. A 35-year-old
      woman was referred to our center for evaluation of cognitive disturbance and
      demyelinating lesions seen on brain magnetic resonance imaging (MRI). We
      performed a neurologic examination, full neuropsychological assessment, brain
      MRI, blood and cerebrospinal fluid analyses, visual evoked potentials, and brain
      biopsy. The patient's Mini-Mental State Examination score was 26/30. Cognitive
      assessment revealed multiple severe dysfunctions, mainly in executive and
      attention tasks. She scored below the normal range on the Digit Span Forward and
      Backward Test and the Trail Making Test Part B. The Frontal Assessment Battery
      showed deficits in mental flexibility, motor programming, and inhibitory control.
      She also scored in the impaired range on tests of verbal fluency and memory. The
      brain MRI and biopsy confirmed a diagnosis of ADEM. This case report points to
      the limitations of relying on clinical presentation, neuroimaging, and current
      controversial diagnostic criteria in diagnosing ADEM in adults, and highlights
      the essential role of pathologic evaluation.

PMID- 23538569
TI  - Challenging behavior in Smith-Lemli-Opitz syndrome: initial test of biobehavioral
      influences.
AB  - OBJECTIVE: To study challenging behavior (destruction, aggression, self-injury,
      stereotypy) in children with Smith-Lemli-Opitz syndrome (SLOS) using a
      biobehavioral model that helps distinguish biological from socially mediated
      variables influencing the behavior. BACKGROUND: SLOS is an autosomal-recessive
      syndrome of multiple malformations and intellectual disability resulting from a
      genetic error in cholesterol synthesis in all cells and tissues, including brain.
      The exact cause of the challenging behavior in SLOS is unclear, but defective
      brain cholesterol synthesis may contribute. Because the precise genetic and
      biochemical etiology of SLOS is known, this disorder is a good model for studying
      biological causes of challenging behavior. METHOD: In a preliminary application
      of a biobehavioral model, we studied the association between cholesterol levels
      (as a biochemical indicator of disease severity) and behavior subtype
      ("biological" vs "learned") in 13 children with SLOS. Parents completed a
      questionnaire that categorized challenging behavior as influenced primarily by
      social or nonsocial (thus, presumably biological) factors. RESULTS: The severity
      of the cholesterol synthesis defect correlated significantly with behavior
      subtype classification for 1 of 2 challenging behaviors. Greater severity of the
      cholesterol synthesis defect was associated with behavior being classified as
      primarily influenced by biological factors. CONCLUSION: The interplay between
      challenging behavior and defective cholesterol synthesis in SLOS may help explain
      biological influences on the behavior. Our findings have implications for
      research on the effectiveness of behavioral and medical treatments for behavioral
      difficulties in SLOS and other neurodevelopmental disorders.

PMID- 23538571
TI  - Neuropsychiatric autoimmune encephalitis without VGKC-complex, NMDAR, and GAD
      autoantibodies: case report and literature review.
AB  - We report a patient with a seronegative autoimmune panencephalitis, adding a
      subtype to the emerging spectrum of seronegative autoimmune encephalitis, and we
      review the sparse literature on isolated psychiatric presentations of autoimmune
      encephalitis. (A PubMed search for "seronegative autoimmune encephalitis,"
      "nonvasculitic autoimmune inflammatory meningoencephalitis," and related terms
      revealed <25 cases.) A 15-year-old girl developed an acute-onset isolated
      psychosis with prominent negative symptoms and intermittent encephalopathy.
      Despite clinical worsening, her brain magnetic resonance imaging (MRI) scans
      remained normal for 7 years. Serology was negative for voltage-gated potassium
      channel (VGKC)-complex, N-methyl-D-aspartate receptor (NMDAR), and glutamic acid
      decarboxylase (GAD) autoantibodies. We excluded genetic, metabolic,
      paraneoplastic, degenerative, and infectious etiologies. The patient's symptoms
      remitted fully with immune therapy, but recurred in association with widespread
      bihemispheric brain lesions. Brain biopsy revealed mild nonvasculitic
      inflammation and prominent vascular hyalinization. Immune therapy with plasma
      exchanges cleared the MRI abnormalities but, 10 years after onset, the patient
      still suffers neuropsychiatric sequelae. We conclude that autoimmune
      panencephalitis seronegative for VGKC-complex, NMDAR, and GAD autoantibodies is a
      subtype of autoimmune encephalitis that can present with pure neuropsychiatric
      features and a normal brain MRI. Immunologic mechanisms may account for
      psychiatric symptoms in a subset of patients now diagnosed with classical
      psychotic disorders. Delay in starting immune therapy can lead to permanent
      neuropsychiatric sequelae. We propose a standardized classification system for
      the autoimmune encephalitides, integrating earlier pathology-oriented terms with
      more recently defined serologic and clinical phenotypes.

PMID- 23538572
TI  - Association of paraoxonase 1 L55M and Q192R single-nucleotide polymorphisms with
      age-related macular degeneration.
AB  - PURPOSE: To determine if paraoxonase 1 (PON1) gene polymorphisms have an effect
      on the risk of having age-related macular degeneration (AMD). METHODS: The study
      population consisted of 142 patients who were diagnosed with either exudative or
      atrophic AMD and 138 sex- and age-matched controls without AMD. Genotyping of the
      PON1 L55M and Q192R single-nucleotide polymorphisms was performed using real-time
      polymerase chain reaction and commercially produced kits. A full ophthalmic
      evaluation was performed in each subject, and all subjects were screened for
      hypertension, diabetes, hypercholesterolemia, and smoking history. RESULTS: The
      PON1 MM and QQ genotypes were less frequent in patients with AMD than in control
      subjects (MM: 4 vs. 13%, P = 0.015; QQ: 15 vs. 27%, P = 0.020). A multivariate
      logistic regression analysis was also conducted. After adjusting for age, gender,
      and the prevalence of smoking, hypertension, diabetes, and hypercholesterolemia,
      the MM and QQ genotypes (MM/QQ vs. LL + LM/QR + RR) were found to be associated
      with a decreased risk of AMD (MM: odds ratio = 0.24, P = 0.007, 95% confidence
      interval: 0.09-0.68; QQ: odds ratio = 0.46, P = 0.013, 95% confidence interval:
      0.25-0.85). CONCLUSION: The authors found that subjects with the PON1 MM and QQ
      genotypes had a lower risk of AMD.

PMID- 23538573
TI  - Spectral domain optical coherence tomography-determined morphologic predictors of
      age-related macular degeneration-associated geographic atrophy progression.
AB  - PURPOSE: To correlate spectral domain optical coherence tomography (SD OCT)
      determined morphologic alterations in eyes with geographic atrophy because of age
      related macular degeneration with lesion size, enlargement rate, and the presence
      of multifocal patches of atrophy. METHODS: Forty-three eyes of 43 patients with
      age-related macular degeneration-associated geographic atrophy were visualized by
      SD OCT and fundus autofluorescence imaging. The baseline area of geographic
      atrophy and enlargement rates over at least 24 weeks were calculated from the
      fundus autofluorescence images. The mean and median follow-up times were 47.4 and
      48 weeks, respectively. Morphologic alterations were evaluated in the baseline SD
      OCT images. Ninety-seven SD OCT scans per eye were graded and included in the
      analysis. Correlations between morphologic alterations and the rate of lesion
      enlargement, size, and focality, and the diffuse trickling fundus
      autofluorescence pattern were determined. RESULTS: The mean and median
      enlargement rates were 2.07 mm(2)/year (n = 43; SD, 1.30) and 2.02 mm(2)/year,
      respectively. Outer retinal tubulations (P = 0.003) and irregular elevations of
      the retinal pigment epithelium/Bruch membrane complex (P < 0.001) in the atrophic
      region, and splitting of the retinal pigment epithelium/Bruch membrane complex at
      2 junctional zone borders (P = 0.02) correlated with faster enlargement. Outer
      retinal tubulations (P = 0.096), irregular elevations of the retinal pigment
      epithelium/Bruch membrane complex (P = 0.010), and crown-like elevations with
      debris beneath in the atrophic region (P = 0.063) correlated with larger lesion
      size. Hyperreflective plaques in the outer retina appeared more frequently in
      eyes with multifocal patches of atrophy (P = 0.005). CONCLUSION: Distinct
      morphologic alterations visible on SD OCT imaging in eyes with geographic atrophy
      because of age-related macular degeneration are associated with faster
      enlargement rates, larger lesion size, and multifocal patches of atrophy.

PMID- 23538574
TI  - Interocular symmetry of parafoveal photoreceptor cone density distribution.
AB  - PURPOSE: To investigate the variation and symmetry of cone density distribution
      along the nasal and temporal retina of fellow eyes. METHODS: An adaptive optics
      retinal camera (rtx1; Imagine Eyes) was used to obtain images of the parafoveal
      cone mosaic in 20 healthy subjects. Cone density was estimated at 250, 420, 760,
      and 1,300 MUm eccentricity from the fovea along the nasal and temporal retina of
      both eyes in each subject. The coefficient of variation and the intraclass
      correlation coefficient were used to calculate the variation and absolute
      agreement of cone density between the same retinal eccentricity locations of
      fellow eyes, respectively. RESULTS: A considerable variation of cone density
      between subjects was found at all eccentricities along the nasal and temporal
      retina (intersubject coefficient of variation >= 11%, P < 0.001). The
      intrasubject variation of cone density was, however, moderate (coefficient of
      variation <= 13% in 95% of the subjects); a high agreement was, on average, found
      between the cone density estimates at the same eccentricity along the nasal and
      temporal retina of fellow eyes (intraclass correlation coefficient >= 0.86, P <
      0.001). CONCLUSION: Cone density follows a symmetrical distribution between
      fellow eyes. A systematic distribution of parafoveal cones between fellow eyes
      may provide an anatomical basis for the involvement of the photoreceptor layer in
      the first step of binocular spatial sampling.

PMID- 23538575
TI  - Reproducibility and repeatability of Cirrus and Spectralis Fourier-domain optical
      coherence tomography of healthy and epiretinal membrane eyes.
AB  - PURPOSE: To evaluate the accuracy and reproducibility of retinal thickness
      measurements in healthy and epiretinal membranes (ERM) eyes by Cirrus and
      Spectralis Fourier-domain optical coherence tomography devices. METHODS: Eighty
      seven ERM and 122 healthy subjects underwent 3 macular scans using both optical
      coherence tomography instruments. Mean thickness measurements in the nine Early
      Treatment Diabetic Retinopathy Study areas were compared, evaluating the
      repeatability and the relationship between devices. RESULTS: Macular thickness
      increase was detected in ERM eyes for all optical coherence tomography parameters
      (P < 0.001). Mean foveal thickness was 423.5 +/- 81.4 and 438.0 +/- 54.2 MUm for
      ERM eyes and 267.1 +/- 20.2 and 277.5 +/- 18.9 MUm for healthy eyes using Cirrus
      and Spectralis, respectively. Macular average thickness in ERM eyes as determined
      by both optical coherence tomography was correlated (r = 0.812; P < 0.001) but
      significantly different (P = 0.044). In ERM eyes, measurements showed a mean of
      the coefficients of variation of 2.95%, 2.2%, and 1.01% using Cirrus, Spectralis,
      and Spectralis progression feature, respectively. Intraclass correlation
      coefficients were higher than 0.919 in all cases. CONCLUSION: Reproducibility of
      both Cirrus and Spectralis optical coherence tomography was high in healthy and
      ERM eyes. However, considerable differences were found between macular thickness
      measurements obtained by both devices despite the high correlation between them.

PMID- 23538576
TI  - "Multimodality imaging of hydrogel scleral buckles".

PMID- 23538577
TI  - Outer retinal tubulation in inherited retinal degenerative disease.
AB  - PURPOSE: To investigate the prevalence and characteristics of outer retinal
      tubulation (ORT) seen in inherited retinal degenerative diseases. METHODS: A
      total of 354 eyes of 177 patients were examined with spectral domain optical
      coherence tomography. One hundred and twelve patients had retinitis pigmentosa,
      58 patients had cone dystrophy, and 7 patients had the Bietti crystalline
      dystrophy. The images obtained by horizontal and vertical scans were analyzed to
      explore the possible presence of ORT, estimate their prevalence, morphologic
      character, and their location in the retinal layers. RESULTS: With spectral
      domain optical coherence tomography, ORT was identified in 0 of 112 patients with
      retinitis pigmentosa, unilaterally in 3 of 58 patients with cone dystrophy, and
      bilaterally in 5 of 7 patients with the Bietti crystalline dystrophy. Outer
      retinal tubulation was detected under the fovea, and in the outer nuclear layer,
      ORT was detected in the Bietti crystalline dystrophy with a significantly higher
      frequency than in cone dystrophy (P < 0.001). CONCLUSION: There was a higher rate
      of ORT in the Bietti crystalline dystrophy among inherited retinal degenerative
      diseases.

PMID- 23538578
TI  - A 12-month prospective trial of inject and extend regimen for ranibizumab
      treatment of age-related macular degeneration.
AB  - PURPOSE: To evaluate the safety and efficacy of a strictly applied inject and
      extend protocol for ranibizumab treatment of age-related macular degeneration.
      METHODS: This is a prospective, multicenter, nonrandomized trial. Patients
      underwent standard induction with 3 intravitreal doses of 0.5 mg ranibizumab,
      each 1 month apart. Following this induction, patients were evaluated and
      received an injection at each visit. If they did not meet set criteria for signs
      of exudative disease the interval to the next visit was extended by 2 weeks and
      if exudative disease was present the interval was shortened by 2 weeks. RESULTS:
      Vision improved by 1.3 lines (P = 0.008); 26% gained >=3 lines of vision, 74%
      lost no lines of vision, and 95% avoided loss of >=3 lines of vision. CONCLUSION:
      This study shows that the Inject and Extend protocol is safe and efficacious for
      the treatment of age-related macular degeneration. Head-to-head studies are
      needed to compare directly with other regimens currently in use, as well as
      economic analysis to investigate the financial implications.

PMID- 23538580
TI  - Inverted hypopyon in the posterior pole.

PMID- 23538579
TI  - Preclinical evaluation and intraoperative human retinal imaging with a high
      resolution microscope-integrated spectral domain optical coherence tomography
      device.
AB  - PURPOSE: The authors have recently developed a high-resolution microscope
      integrated spectral domain optical coherence tomography (MIOCT) device designed
      to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of
      this report is to describe translation of this device from preclinical testing
      into human intraoperative imaging. METHODS: Before human imaging, surgical
      conditions were fully simulated for extensive preclinical MIOCT evaluation in a
      custom model eye system. Microscope-integrated spectral domain OCT images were
      then acquired in normal human volunteers and during vitreoretinal surgery in
      patients who consented to participate in a prospective institutional review board
      approved study. Microscope-integrated spectral domain OCT images were obtained
      before and at pauses in surgical maneuvers and were compared based on
      predetermined diagnostic criteria to images obtained with a high-resolution
      spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same
      time point. Cohorts of five consecutive patients were imaged. Successful end
      points were predefined, including >=80% correlation in identification of
      pathology between MIOCT and HHOCT in >=80% of the patients. RESULTS: Microscope
      integrated spectral domain OCT was favorably evaluated by study surgeons and
      scrub nurses, all of whom responded that they would consider participating in
      human intraoperative imaging trials. The preclinical evaluation identified
      significant improvements that were made before MIOCT use during human surgery.
      The MIOCT transition into clinical human research was smooth. Microscope
      integrated spectral domain OCT imaging in normal human volunteers demonstrated
      high resolution comparable to tabletop scanners. In the operating room, after an
      initial learning curve, surgeons successfully acquired human macular MIOCT images
      before and after surgical maneuvers. Microscope-integrated spectral domain OCT
      imaging confirmed preoperative diagnoses, such as full-thickness macular hole and
      vitreomacular traction, and demonstrated postsurgical changes in retinal
      morphology. Two cohorts of five patients were imaged. In the second cohort, the
      predefined end points were exceeded with >=80% correlation between microscope
      mounted OCT and HHOCT imaging in 100% of the patients. CONCLUSION: This report
      describes high-resolution MIOCT imaging using the prototype device in human eyes
      during vitreoretinal surgery, with successful achievement of predefined end
      points for imaging. Further refinements and investigations will be directed
      toward fully integrating MIOCT with vitreoretinal and other ocular surgery to
      image surgical maneuvers in real time.

PMID- 23538581
TI  - Spectral domain optical coherence tomography analysis of macular changes in
      tilted disk syndrome.
AB  - PURPOSE: To evaluate the prevalence of macular complications in tilted disk
      syndrome by spectral domain optical coherence tomography (OCT). METHODS: A
      monocentric retrospective study of consecutive patients with tilted disk
      syndrome, whose eyes were examined by spectral domain OCT (Cirrus; Zeiss) and
      fundus photography. RESULTS: Fifty consecutive patients (39 women and 11 men; age
      range, 41-96 years) with uni- or bilateral tilted disk syndrome were enrolled.
      All affected eyes (n = 92) were imaged by spectral domain OCT and fundus
      photography. Fluorescein and/or indocyanine green angiography were performed in
      33 patients (66%). Macular anomalies or complications were observed in 71 eyes
      (77.1%). Specifically, retinal pigment epithelial changes were described in 34
      eyes (36.9%), choroidal neovascularization in 24 eyes (26%), and macular serous
      retinal detachment in 16 eyes (17.3%). Epiretinal membrane in 9 eyes (9.7%),
      myopic foveoschisis in 5 eyes (5.4%), and lamellar macular hole in 3 eyes (3.2%)
      were also detected relatively frequently by spectral domain OCT. Surprisingly,
      fovea plana was observed in 5 eyes (5.4%). Eleven eyes, complicated by choroidal
      neovascularization, were treated with ranibizumab, with a mean visual gain of 7.9
      letters on Early Treatment Diabetic Retinopathy Study chart. CONCLUSION: Tilted
      disk syndrome can be associated with potentially severe macular complications.
      Spectral domain OCT allowed the recognition of additional macular changes
      associated with tilted disk syndrome, such as epiretinal membranes, myopic
      foveoschisis, and fovea plana.

PMID- 23538582
TI  - Plus disease diagnosis in retinopathy of prematurity: vascular tortuosity as a
      function of distance from optic disk.
AB  - PURPOSE: To examine vascular tortuosity as a function of distance from the optic
      disk in infants with retinopathy of prematurity. METHODS: Thirty-four wide-angle
      retinal images from infants with retinopathy of prematurity were reviewed by 22
      experts. A reference standard for each image was defined as the diagnosis (plus
      vs. not plus) given by the majority of experts. Tortuosity, defined as vessel
      length divided by straight line distance between vessel end points, was
      calculated as a function of distance from the disk margin for arteries and veins
      using computer-based methods developed by the authors. RESULTS: Mean cumulative
      tortuosity increased with distance from the disk margin, both in 13 images with
      plus disease (P = 0.007 for arterial tortuosity [n = 62 arteries], P < 0.001 for
      venous tortuosity [n = 58 veins] based on slope of best fit line by regression),
      and in 21 images without plus disease (P < 0.001 for arterial tortuosity [n = 94
      arteries], P <0 .001 for venous tortuosity [n = 85 veins]). Images with plus
      disease had significantly higher vascular tortuosity than images without plus
      disease (P < 0.05), up to 7.0 disk diameters from the optic disk margin.
      CONCLUSION: Vascular tortuosity was higher peripherally than centrally, both in
      images with and without plus disease, suggesting that peripheral retinal features
      may be relevant for retinopathy of prematurity diagnosis.

PMID- 23538583
TI  - Risk factors, anatomical, and visual outcomes of injured eyes with proliferative
      vitreoretinopathy: eye injury vitrectomy study.
AB  - PURPOSE: To investigate potential risk factors for development of proliferative
      vitreoretinopathy (PVR) post trauma and evaluate the effect of PVR on anatomical
      and visual outcomes in injured eyes. METHODS: Overall, 179 eyes with PVR and 221
      eyes without PVR after injury were selected from the database of the Eye Injury
      Vitrectomy Study, a multicenter cohort study launched in 1997. Multivariate
      logistic regression was used to ascertain the independent risk factors for
      development of PVR and to evaluate the influence of PVR on anatomical and visual
      outcomes. RESULTS: An interval of injury and vitrectomy of more than 28 days
      (odds ratio, 139.25; confidence interval, 50.09-387.10), severe vitreous
      hemorrhage (odds ratio, 2.72; confidence interval, 1.13-6.52), and total retinal
      detachment (odds ratio, 12.67; confidence interval, 3.96-40.52) were important
      independent risk factors for PVR. One hundred and fifteen eyes (52.0%) and 49
      eyes (27.4%) without and with PVR, respectively, were anatomically restored with
      ambulant visual acuity (>=4/200). Proliferative vitreoretinopathy, poor initial
      visual acuity, relative afferent pupillary defect, total retinal detachment, and
      retinal tear or retinal defect were unfavorable prognostic indicators.
      CONCLUSION: Proliferative vitreoretinopathy occurs frequently in injured eyes and
      is associated with poor outcomes. Its onset depends on interval of injury and
      vitrectomy, wound location, vitreous hemorrhage, and retinal detachment. Early
      vitrectomy (before 2 weeks) and aggressive therapy should be considered for
      specific high-risk cases.

PMID- 23538584
TI  - Repeated intravitreal bevacizumab injection with and without macular grid
      photocoagulation for treatment of diffuse diabetic macular edema.
AB  - PURPOSE: To study whether the use of macular grid photocoagulation 3 weeks
      subsequent to the initial intravitreal bevacizumab (IVB) injection for the
      treatment of diffuse diabetic macular edema can provide a longer disease-free
      intervals and reduce the burden of more frequent injections. METHODS: A
      prospective pilot study that included 22 patients with bilateral diffuse diabetic
      macular edema. In each patient, one eye was treated with repeated IVB injections
      alone (IVB group), while the other eye was treated with repeated IVB injections
      in addition to macular grid photocoagulation once only 3 weeks after the initial
      IVB injection (combined group). Before each IVB injection and during the follow
      up visits, all patients received a complete ophthalmic examination. The central
      macular thickness was measured by optical coherence tomography at baseline and
      during the follow-up examinations. Fundus fluorescein angiography was performed
      at baseline and before each IVB injection, to detect and assess macular leakage.
      All patients were followed-up monthly for at least 12 months after the initial
      IVB injection and for 3 months after the last IVB injection. RESULTS: By the end
      of the follow-up duration (14.2 +/- 1.91 months), the mean number of injections
      was significantly lower (P < 0.05) in the combined group (2.36 per eye) than in
      the IVB group (3.27 per eye). The mean duration between the injections was
      significantly longer in the combined group than in the IVB group (P < 0.05).
      Within each group, the difference between the mean central macular thickness at
      the baseline and at the end of the follow-up duration was statistically
      significant (P < 0.05). The change in the mean best-corrected visual acuity
      between the baseline and the end of the follow-up period was not statistically
      significant in both the groups (P > 0.05). There was no statistically significant
      difference between the 2 groups of the study as regards the number of patients
      who gained, maintained, or lost vision (P > 0.05). CONCLUSION: Repeated IVB
      injection could provide a long-term benefit for the treatment of diffuse diabetic
      macular edema. Performing macular grid photocoagulation once only 3 weeks
      subsequent to the initial IVB injection might provide a longer disease-free
      intervals and reduces the burden of more frequent injections.

PMID- 23538585
TI  - Adaptive optics for retinal imaging: current status.

PMID- 23538586
TI  - Reliability of isometric lower-extremity muscle strength measurements in children
      with cerebral palsy: implications for measurement design.
AB  - BACKGROUND: Children with cerebral palsy (CP) typically show muscle weakness of
      the lower extremities, which can be measured with the use of handheld dynamometry
      (HHD). OBJECTIVE: The purposes of this study were: (1) to determine test-retest
      reliability and measurement error of isometric lower-extremity strength
      measurements in children with CP with the use of HHD and (2) to assess
      implications for measurement design. DESIGN: A test-retest design was used.
      METHODS: Fourteen children with hemiplegic (n=6) or diplegic (n=8) spastic CP
      (Gross Motor Function Classification System levels I-III), ages 7 to 13 years,
      were assessed for isometric strength on 2 separate days (occasions) with the use
      of HHD, with 3 trials per muscle group. The intraclass correlation coefficient,
      standard error of measurement, and smallest detectable difference (SDD) were
      calculated for different measurement designs. RESULTS: Intraclass correlation
      coefficient values of single measurements for all muscle groups ranged from .70
      to .90, and the SDD was large (>30%). Regarding measurement error, the largest
      source of variability was found for occasion. A 2-occasion mean decreased the SDD
      by 9% to 14%. For trials, a greater improvement in SDD was found when 2 trials
      were averaged instead of 3. A measurement design of 2 trials-2 occasions was
      superior to the often-used approach of 3 trials-1 occasion. LIMITATIONS: The
      small sample size was the major study limitation. CONCLUSIONS: Handheld
      dynamometry is reliable and can be used to detect changes in isometric muscle
      strength in children with CP when using the mean of at least 2 trials. To further
      improve reliability, taking the average of 2 occasions on separate days is
      recommended, depending on group size and muscle group.

PMID- 23538587
TI  - Toward understanding normal craniocervical rotation occurring during the rotation
      stress test for the alar ligaments.
AB  - BACKGROUND: The rotation stress test is recommended for assessing alar ligament
      integrity. Although some authors, in the literature regarding the rotation stress
      test, accept that rotation will occur during testing, estimates of range
      occurring with a normal test response vary between 20 and 40 degrees. None of
      these estimates are based on formal examination of the test. OBJECTIVE: The
      purposes of this study were: (1) to examine the range of craniocervical rotation
      occurring during rotation stress testing for the alar ligaments in individuals
      who are healthy and (2) to investigate a measurement protocol for quantifying
      rotation. DESIGN: A within-subject experimental study was conducted. METHODS:
      Sixteen participants underwent magnetic resonance imaging in neutral and end
      range rotation stress test positions. Measurements followed a standardized
      protocol relative to the position of the axis. A line connecting the transverse
      foramena of the axis created a reference plane. The position of the occiput in
      the head-neutral position was calculated as the angle formed between a line
      joining the foramena lacerum and the reference plane. Measurements were repeated
      at the end-range test position. Total rotation of the occiput was calculated as
      the difference in angles measured in neutral and test positions. Measurement was
      performed on 4 occasions, and reliability of measurements was assessed using the
      standard error of measurement (SEM) and the intraclass correlation coefficient
      (ICC). RESULTS: Measurement of rotation of the occiput relative to a stabilized
      axis ranged between 1.7 and 21.5 degrees (X=10.6, SD=5.1, SEM=1.14, ICC=.96, 95%
      confidence interval=.90-.98). LIMITATIONS: Sustaining the test position for
      imaging increased the potential for loss of end-range position and image quality.
      Testing could be performed only in the neutral position, not in 3 planes as
      commonly described. CONCLUSIONS: The range of craniocervical rotation during
      rotation stress testing of intact alar ligaments should typically be 21 degrees
      or less. Rotation may be quantified using the method protocol outlined.

PMID- 23538588
TI  - Internationalization of universities: the need to navigate in foreign waters.

PMID- 23538589
TI  - Flexible intramedullary nails with traction versus plaster cast for treating
      femoral shaft fractures in children: comparative retrospective study.
AB  - CONTEXT AND OBJECTIVE Femoral fractures are common in children between 2 and 12
      years of age, and 75% of the lesions affect the femoral shaft. Traction followed
      by a plaster cast is universally accepted as conservative treatment. However, in
      some situations, a surgical approach is recommended. The objective here was to
      compare treatments for femoral shaft fractures using intramedullary nails
      (titanium elastic nails, TEN) versus traction and plaster casts in children. The
      hypothesis was that TEN might provide better treatment, with good clinical
      results in comparison with plaster casts. DESIGN AND SETTING This retrospective
      comparative study was conducted in a public university hospital. METHODS Sixty
      children with femoral fractures were evaluated; 30 of them underwent surgical
      treatment with TEN and 30 were treated conservatively using plaster casts. The
      patients' ages ranged from 5 to 13 years (mean of 9 years). RESULTS The mean
      duration of hospitalization was nine days for the surgical group and 20 days for
      the conservative group. The incidence of overgrowth in the patients treated with
      TEN was 60.0% and, for those treated conservatively, 13.3%. Partial weight
      bearing was allowed after 3.5 weeks in the surgical group and after 9.6 weeks in
      the conservative group. New hospitalization was required for 90.0% in the
      surgical group and 16.7% in the conservative group. Patients treated with plaster
      casts presented higher incidence of complications, such as loss of reduction.
      CONCLUSIONS The surgical method presented better results for children.

PMID- 23538590
TI  - Elderly outpatient profile and predictors of falls.
AB  - CONTEXT AND OBJECTIVES Falls are a serious public health problem and are one of
      the biggest reasons for hospitalization, morbidity and mortality among elderly
      people. Moreover, few studies on predictors of falls have been conducted in low
      and middle income countries. The aim here was to identify elderly outpatient
      profiles according to sociodemographic, clinical, physical and functional
      variables and correlate them with occurrences of falls among these subjects.
      DESIGN AND SETTING Cross-sectional descriptive study forming part of the project
      "Quality of Life of Frail Elderly People", carried out in Campinas, Brazil.
      METHODS The subjects were 145 elderly individuals (76.3 +/- 7.8 years old), of
      whom 65% were women, who were living in the city of Campinas or nearby and were
      attended at the geriatric outpatient clinic of a University Hospital.
      Sociodemographic, clinical, physical and functional data, as well as fall
      occurrence data, were gathered. Cluster analyses and comparisons between groups
      were carried out. RESULTS Cluster analysis identified two distinct groups related
      to the study variables, and the determinants for this distinction were: gender,
      marital status, physical performance, handgrip strength and functional
      independence. These groups were compared according to occurrences of falls over
      the last year, and significant differences between them were found. CONCLUSIONS
      The results showed that greater occurrences of falls were associated with a
      profile of elderly people comprising female gender, single status, lower muscle
      strength and physical performance regarding balance and gait, and lower
      independence in motor tasks for activities of daily living.

PMID- 23538591
TI  - Potentially inappropriate medications among elderly Brazilian outpatients.
AB  - CONTEXT AND OBJECTIVES In Brazil, few studies have investigated the prevalence of
      potentially inappropriate medications (PIMs) among elderly outpatients. This
      study aimed to determine the prevalence of PIMs prescribed for elderly
      outpatients, identify the PIMs most commonly involved, and investigate whether
      age, sex and number of medications are related to prescription of such
      medications. DESIGN AND SETTING Observational descriptive study developed in the
      Geriatrics Service of the Central Institute of Hospital das Clinicas (HC),
      Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil.
      METHODS Prescriptions issued to 1,270 elderly patients (>= 60 years) were
      gathered from a database. These prescriptions had been written by geriatricians
      at a tertiary-level university hospital in Sao Paulo, Brazil, between February
      and May 2008. The prescriptions were divided according to sex and age group (60
      69, 70-79 and >= 80). The Beers criteria were used to evaluate PIMs. RESULTS Most
      of the sample comprised women (77%) and the mean age was 80.1 years. The mean
      prevalence of PIM prescriptions was 26.9%. Female sex and number of medications
      prescribed were associated with prescription of PIMs. The chance of having a PIM
      prescription was lower among patients >= 70 years. CONCLUSION The greater
      prevalence of PIMs was correlated with female sex. The chance of having a PIM
      prescription was lower among patients >= 70 years and became greater with
      increasing numbers of medications prescribed (>= 7).

PMID- 23538592
TI  - Risk factors for esophageal cancer in a low-incidence area of Brazil.
AB  - CONTEXT AND OBJECTIVES Esophageal cancer is the eighth commonest type of cancer
      worldwide, occupying sixth place in terms of mortality. Smoking and alcohol use
      are known risk factors for this type of cancer. The aim here was to evaluate the
      risk factors for esophageal cancer in a low-incidence area. DESIGN AND SETTING
      Case-control study in Goiania, with 99 cases of esophageal cancer and 223
      controls. METHODS The variables were sociodemographic, dietary, occupational and
      lifestyle data. The sample was analyzed using the chi-square test, Mann-Whitney
      test and Mantel-Haenszel approach for multivariate analysis. Odds ratios (OR)
      were calculated with 5% significance and 95% confidence intervals. RESULTS The
      risk of esophageal cancer was higher in patients >= 55 years (OR = 1.95; P <
      0.001). Patients from rural areas were at greater risk of esophageal cancer (OR =
      4.9; P < 0.001). Smoking was a risk factor among the cases (OR = 3.8; P < 0.001),
      as was exposure to woodstoves (OR = 4.42; P < 0.001). The practice of oral sex
      was not a risk factor (OR = 0.45; P = 0.04). Consumption of apples, pears,
      vegetables, cruciferous vegetables and fruit juices were protective against
      esophageal cancer. CONCLUSION In a region in which the incidence of esophageal
      cancer is low, the most significant risk factors were exposure to woodstoves,
      smoking and living in rural areas.

PMID- 23538593
TI  - Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot
      randomized clinical trial.
AB  - CONTEXT AND OBJECTIVE Oxaliplatin is one of the chemotherapy regimens most used
      for treating colorectal cancer. One of the main limitations to its use is
      induction of peripheral neuropathy. Previous studies have shown that vitamin E
      can reduce the incidence of peripheral neuropathy by 50%. This study aimed to
      assess the effectiveness of vitamin E for prevention of oxaliplatin-induced
      peripheral neuropathy. DESIGN AND SETTING Prospective, phase II, randomized pilot
      study developed at a university hospital in the Greater ABC region. METHODS
      Patients were randomized five days before starting oxaliplatin treatment, to
      receive either vitamin E or placebo until the end of the chemotherapy regimen.
      The outcome was evaluated using the Common Terminology Criteria for Adverse
      Events (CTCAE), version 3, and specific gradation scales for oxaliplatin-induced
      peripheral neuropathy. Patients with colorectal and gastric cancer who had been
      scheduled to receive oxaliplatin-based chemotherapy were included. Both groups
      received calcium and magnesium supplementation before and after oxaliplatin
      infusions. RESULTS Eighteen patients were randomized to the vitamin E group and
      16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy
      grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group
      (P = 0.45). A trend towards more diarrhea was observed among patients who
      received vitamin E (55.6% vs. 18.8%; P = 0.06). There were no other significant
      differences in toxicity between the groups. CONCLUSIONS No significant decrease
      in the incidence of acute oxaliplatin-induced peripheral neuropathy was
      demonstrated through vitamin E use.

PMID- 23538594
TI  - Mapping of the evidence from systematic reviews of the Cochrane Collaboration for
      decision-making within physiotherapy.
AB  - CONTEXT AND OBJECTIVE Evidence-based clinical practice emerged with the aim of
      guiding clinical issues in order to reduce the degree of uncertainty in decision
      making. The Cochrane Collaboration has been developing systematic reviews on
      randomized controlled trials as high-quality intervention study subjects. Today,
      physiotherapy methods are widely required in treatments within many fields of
      healthcare. Therefore, it is extremely important to map out the situation
      regarding scientific evidence within physiotherapy. The aim of this study was to
      identify systematic reviews on physiotherapeutic interventions and investigate
      the scientific evidence and recommendations regarding whether further studies
      would be needed. TYPE OF STUDY AND SETTING Cross-sectional study conducted within
      the postgraduate program on Internal Medicine and Therapeutics and at the
      Brazilian Cochrane Center. METHODS Systematic reviews presenting
      physiotherapeutic interventions as the main investigation, in the Cochrane
      Reviews Group, edition 2/2009, were identified and classified. RESULTS Out of the
      3,826 reviews, 207 (5.41%) that fulfilled the inclusion criteria were selected.
      Only 0.5% of the reviews concluded that the intervention presented a positive
      effect and that further studies were not recommended; 45.9% found that there
      seemed to be a positive effect but recommended further research; and 46.9% found
      that the evidence was insufficient for clinical practice and suggested that
      further research should be conducted. CONCLUSION Only one systematic review
      ("Pulmonary rehabilitation for chronic obstructive pulmonary disease") indicated
      that the intervention tested could be used with certainty that it would be
      effective. Most of the systematic reviews recommended further studies with
      greater rigor of methodological quality.

PMID- 23538595
TI  - Calcium renal lithiasis: metabolic diagnosis and medical treatment.
AB  - Calcium renal lithiasis is a frequent condition that affects the worldwide
      population and has a high recurrence rate. Different metabolic changes may
      trigger the onset of calcium stone disorders, such as hypercalciuria,
      hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other
      very prevalent disorders that are associated with calcium calculi, such as
      arterial hypertension, obesity and loss of bone mineral density. A correct
      diagnosis needs to be obtained through examining the serum and urinary parameters
      of mineral metabolism in order to carry out adequate prevention and treatment of
      this condition. Once the metabolic diagnosis is known, it is possible to
      establish dietary and pharmacological treatment that may enable monitoring of the
      disease and prevent recurrence of stone formation. Some advances in treating this
      pathological condition have been made, and these include use of sodium
      alendronate in patients with calcium renal lithiasis and osteopenia/osteoporosis,
      or use of a combination of a thiazide with a bisphosphonate. In summary, calcium
      renal lithiasis often requires multidrug treatment with strict control and follow
      up of patients.

PMID- 23538596
TI  - Penile enlargement with methacrylate injection: is it safe?
AB  - CONTEXT Penis size is a great concern for men in many cultures. Despite the great
      variety of methods for penile augmentation, none has gained unanimous acceptance
      among experts in the field. However, in this era of minimally invasive procedure,
      injection therapy for penile augmentation has become more popular. Here we report
      a case of methacrylate injection in the penis that evolved with penile deformity
      and sexual dysfunction. This work also reviews the investigation and management
      of this pathological condition. CASE REPORT A 36-year-old male sought medical
      care with a complaint of penile deformity and sexual dysfunction after
      methacrylate injection. The treatment administered was surgical removal.
      Satisfactory cosmetic and functional results were reached after two months.
      CONCLUSIONS There is a need for better structured scientific research to evaluate
      the outcomes and complication rates from all penile augmentation procedures.

PMID- 23538597
TI  - Bacteremia due to Staphylococcus cohnii ssp. urealyticus caused by infected
      pressure ulcer: case report and review of the literature.
AB  - CONTEXT Coagulase-negative staphylococci are common colonizers of the human skin
      and have become increasingly recognized as agents of clinically significant
      nosocomial infections. CASE REPORT The case of a 79-year-old male patient with
      multi-infarct dementia who presented systemic inflammatory response syndrome is
      reported. This was attributed to bacteremia due to Staphylococcus cohnii ssp.
      urealyticus, which was grown on blood cultures originating from an infected
      pressure ulcer. The few cases of Staphylococcus cohnii infection reported in the
      literature consist of bacteremia relating to catheters, surgical prostheses,
      acute cholecystitis, brain abscess, endocarditis, pneumonia, urinary tract
      infection and septic arthritis, generally presenting a multiresistant profile,
      with nearly 90% resistance to methicillin. CONCLUSIONS The reported case is, to
      our knowledge, the first case of true bacteremia due to Staphylococcus cohnii
      subsp. urealyticus caused by an infected pressure ulcer. It shows that this
      species may be underdiagnosed and should be considered in the differential
      diagnosis for community-acquired skin infections.

PMID- 23538598
TI  - The use of telemedicine with patients in clinical practice: the view of medical
      psychology.

PMID- 23538599
TI  - Indicators of mitochondrial disease.

PMID- 23538600
TI  - Interventions for primary (intrinsic) tracheomalacia in children.
AB  - BACKGROUND Tracheomalacia, a disorder of the large airways where the trachea is
      deformed or malformed during respiration, is commonly seen in tertiary paediatric
      practice. It is associated with a wide spectrum of respiratory symptoms from life
      threatening recurrent apnoea to common respiratory symptoms such as chronic cough
      and wheeze. Current practice following diagnosis of tracheomalacia includes
      medical approaches aimed at reducing associated symptoms of tracheomalacia,
      ventilation modalities of continuous positive airway pressure (CPAP) and bi-level
      positive airway pressure (BiPAP), and surgical approaches aimed at improving the
      calibre of the airway (airway stenting, aortopexy, tracheopexy). OBJECTIVES To
      evaluate the efficacy of medical and surgical therapies for children with
      intrinsic (primary) tracheomalacia. METHODS Search The Cochrane Airways Group
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), the
      Cochrane Airways Group's Specialized Register, Medline and Embase databases. The
      Cochrane Airways Group performed the latest searches in March 2012. Selection
      criteria All randomized controlled trials (RCTs) of therapies related to symptoms
      associated with primary or intrinsic tracheomalacia. Data collection and analysis
      Two reviewers extracted data from the included study independently and resolved
      disagreements by consensus. MAIN RESULTS We included one RCT that compared
      nebulized recombinant human deoxyribonuclease (rhDNase) with placebo in 40
      children with airway malacia and a respiratory tract infection. We assessed it to
      be a RCT with overall low risk of bias. Data analyzed in this review showed that
      there was no significant difference between groups for the primary outcome of
      proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval
      (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores
      significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17
      to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline
      was also better in the placebo group compared to those on nebulized rhDNase, but
      the difference between groups was not statistically significant (MD 0.70; 95% CI 
      0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum
      scores, and lung function tests at two weeks also favoured placebo over nebulized
      rhDNase but did not reach levels of significance. AUTHORS' CONCLUSIONS There is
      currently an absence of evidence to support any of the therapies currently
      utilised for management of intrinsic tracheomalacia. It remains inconclusive
      whether the use of nebulized rhDNase in children with airway malacia and a
      respiratory tract infection worsens recovery. It is unlikely that any RCT on
      surgically based management will ever be available for children with severe life
      threatening illness associated with tracheomalacia. For those with less severe
      disease, RCTs on interventions such as antibiotics and chest physiotherapy are
      clearly needed. Outcomes of these RCTs should include measurements of the trachea
      and physiological outcomes in addition to clinical outcomes.

PMID- 23538601
TI  - Surgery or embolization for varicoceles in subfertile men.
AB  - BACKGROUND A varicocele is a meshwork of distended blood vessels in the scrotum,
      usually left-sided, due to dilatation of the spermatic vein. Although the concept
      that a varicocele causes male subfertility has been around for more than 50 years
      now, the mechanisms by which a varicocele would affect fertility have not yet
      been satisfactorily explained. Neither is there sufficient evidence to explain
      the mechanisms by which varicocelectomy would restore fertility. Furthermore, it
      has been questioned whether a causal relation exists at all between the
      distension of the pampiniform plexus (a network of many small veins found in the
      human male spermatic cord) and impairment of fertility. OBJECTIVES To evaluate
      the effect of varicocele treatment on live birth and pregnancy rate in subfertile
      couples where the male has a varicocele. METHODS Search We searched the Cochrane
      Menstrual Disorders and Subfertility Group Trials Register (12 September 2003 to
      January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in
      The Cochrane Library Issue 1, 2012), Medline (January 1966 to January 2012),
      Embase (January 1985 to January 2012), PsycINFO (to Week 1 2012) and reference
      lists of articles. In addition, we handsearched specialist journals in the field
      from their first issue until 2012. We also checked cross-references, references
      from review articles and contacted researchers in the field. Selection criteria
      Randomized controlled trials (RCTs) were included if they were relevant to the
      clinical question posed. If they reported pregnancy rates or live birth rates as
      an outcome measure, and if they reported data in treated (surgical ligation or
      radiological embolization of the internal spermatic vein) compared to untreated
      or placebo groups. Two authors independently screened potentially relevant
      trials. Any differences of opinion were resolved by consensus (none occurred for
      this review). Data collection and analysis Ten studies met the inclusion criteria
      for the review. For one study we had only data from a published abstract. All ten
      studies only included men from couples with subfertility problems; one excluded
      men with sperm counts less than 5 million per mL and one excluded men with sperm
      counts less than 2 million per mL, with or without progressive motility of less
      than 10%. Two trials involving clinical varicoceles included some men with normal
      semen analysis. Three studies specifically addressed only men with subclinical
      varicoceles. Studies were excluded from meta-analysis if they made comparisons
      other than those specified above. MAIN RESULTS The meta-analysis included 894
      men. No studies reported live birth. The combined fixed-effect odds ratio (OR) of
      the 10 studies for the outcome of pregnancy was 1.47 (95% confidence interval
      (CI) 1.05 to 2.05, very low quality evidence), favouring the intervention. The
      number needed to treat for an additional beneficial outcome was 17, suggesting
      benefit of varicocele treatment over expectant management for pregnancy rate in
      subfertile couples in whom varicocele in the man was the only abnormal finding.
      Omission of the studies including men with normal semen analysis and subclinical
      varicocele, some of which had semen analysis improvement as the primary outcome
      rather than live birth or pregnancy rate, was the subject of a planned subgroup
      analysis. The outcome of the subgroup analysis (five studies) also favoured
      treatment, with a combined OR 2.39 (95% CI 1.56 to 3.66). The number needed to
      treat for an additional beneficial outcome was 7. The evidence was suggestive
      rather than conclusive, as the main analysis was subject to fairly high
      statistical heterogeneity (I2 = 67%) and findings were no longer significant when
      a random-effects model was used or when analysis was restricted to higher quality
      studies. AUTHOR' CONCLUSIONS There is evidence suggesting that treatment of a
      varicocele in men from couples with otherwise unexplained subfertility may
      improve a couple's chance of pregnancy. However, findings are inconclusive as the
      quality of the available evidence is very low and more research is needed with
      live birth or pregnancy rate as the primary outcome.

PMID- 23538602
TI  - Hereditary ataxias: overview.
AB  - The hereditary ataxias are a highly heterogeneous group of disorders
      phenotypically characterized by gait ataxia, incoordination of eye movements,
      speech, and hand movements, and usually associated with atrophy of the
      cerebellum. There are more than 35 autosomal dominant types frequently termed
      spinocerebellar ataxia and typically having adult onset. The most common subtypes
      are spinocerebellar ataxia 1, 2, 3, 6, and 7, all of which are nucleotide repeat
      expansion disorders. Autosomal recessive ataxias usually have onset in childhood;
      the most common subtypes are -Friedreich, ataxia-telangiectasia, ataxia with
      oculomotor apraxia type 1, and ataxia with oculomotor apraxia type 2. Four
      autosomal recessive types have dietary or biochemical treatment modalities
      (ataxia with vitamin E deficiency, cerebrotendinous xanthomatosis, Refsum, and
      coenzyme Q10 deficiency), whereas there are no specific treatments for other
      ataxias. Diagnostic genetic testing is complicated because of the large number of
      relatively uncommon subtypes with extensive phenotypic overlap. However, the best
      testing strategy is based on assessing relative frequencies, ethnic
      predilections, and recognition of associated phenotypic features such as
      seizures, visual loss, or associated movement abnormalities.

PMID- 23538603
TI  - Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells.
AB  - AIM: To investigate the effects of ginsenoside Rh2 on the human pancreatic cancer
      cell line Bxpc-3. METHODS: The human pancreatic cancer cell line Bxpc-3 was
      cultured in vitro and treated with or without ginsenoside Rh2. Growth rates for
      Bxpc-3 cells were assessed by methyl thiazolyl tetrazolium (MTT) and colony
      formation assays. Cell cycle changes were analyzed by flow cytometry. Apoptosis
      was measured by flow cytometry and Hoechst 33258 fluorescence staining. A scratch
      assay and a Matrigel invasion assay were used to detect cell migration and
      invasion. Expression of Bax, Bcl-2, survivin, cyclin D1, matrix metalloproteinase
      (MMP)-2, MMP-9, cleaved caspase-3, caspase-8, and caspase-9 mRNA were determined
      by reverse transcriptase-polymerase chain reaction (RT-PCR). Bax, Bcl-2,
      survivin, cyclin D1, cleaved caspase-3, caspase-8 and caspase-9 protein levels
      were examined by western blotting. Expression of MMP-2 and MMP-9 proteins in
      culture supernatants were determined by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Rh2 significantly inhibited Bxpc-3 cell proliferation in a dose
      and time-dependent manner, as evaluated by the MTT (P < 0.05) and colony
      formation assays (P < 0.05). Compared to the control group, Rh2 significantly
      increased the percentage of Bxpc-3 cells in the G0/G1 phase from 43.32% +/- 2.17%
      to 71.32% +/- 1.16%, which was accompanied by a decrease in S phase (from 50.86%
      +/- 1.29% to 28.48% +/- 1.18%) and G2/M phase (from 5.81% +/- 1.19% to 0.20% +/-
      0.05%) in a dose-dependent manner (P < 0.05), suggesting that Rh2 arrested cell
      cycle progression at the G0/G1 phase, as measured by flow cytometry. Compared to
      the control group, cells treated with Rh2 showed significantly higher apoptosis
      ratios in a dose-dependent manner (percentage of early apoptotic cells: from
      5.29% +/- 2.28% to 38.90% +/- 3.42% (F = 56.20, P < 0.05); percentage of late
      apoptotic cells: from 4.58% +/- 1.42% to 36.32% +/- 2.73% (F = 86.70, P < 0.05).
      Rh2 inhibited Bxpc-3 cell migration and invasion, as detected by scratch wound
      healing assay and Matrigel invasion assay [percentages of scratch wound healing
      for 12 h, 24 h and 48 h (control vs experimental group): 37.3% +/- 4.8% vs 18.30%
      +/- 1.65%, 58.7% +/- 3.5% vs 38.00% +/- 4.09% and 93.83% +/- 4.65% vs 65.50% +/-
      4.09%, respectively; t = 6.489, t = 6.656 and t = 7.926, respectively, P < 0.05;
      the number of cells invading at various concentrations (0 MUmol/L, 35 MUmol/L, 45
      MUmol/L and 55 MUmol/L): 81.10 +/- 9.55, 46.40 +/- 6.95, 24.70 +/- 6.88 and 8.70
      +/- 3.34, respectively (F = 502.713, P < 0.05)]. RT-PCR, western blotting or
      ELISA showed that mRNA and protein expression of Bax, cleaved caspase-3 and
      caspase-9 were upregulated (P < 0.05), while mRNA and protein expression of Bcl
      2, survivin, cyclin D1, MMP-2 and MMP-9 were downregulated (P < 0.05).
      CONCLUSION: Ginsenoside Rh2 inhibits proliferation, migration and invasion and
      induces apoptosis of the human pancreatic cancer cell line Bxpc-3.

PMID- 23538604
TI  - Imaging mRNA expression levels in living cells with PNA.DNA binary FRET probes
      delivered by cationic shell-crosslinked nanoparticles.
AB  - Optical imaging of gene expression through the use of fluorescent antisense
      probes targeted to the mRNA has been an area of great interest. The main
      obstacles to developing highly sensitive antisense fluorescent imaging agents
      have been the inefficient intracellular delivery of the probes and high
      background signal from unbound probes. Binary antisense probes have shown great
      promise as mRNA imaging agents because a signal can only occur if both probes are
      bound simultaneously to the mRNA target site. Selecting an accessible binding
      site is made difficult by RNA folding and protein binding in vivo and the need to
      bind two probes. Even more problematic, has been a lack of methods for efficient
      cytoplasmic delivery of the probes that would be suitable for eventual
      applications in vivo in animals. Herein we report the imaging of iNOS mRNA
      expression in live mouse macrophage cells with PNA.DNA binary FRET probes
      delivered by a cationic shell crosslinked knedel-like nanoparticle (cSCK). We
      first demonstrate that FRET can be observed on in vitro transcribed mRNA with
      both the PNA probes and the PNA.DNA hybrid probes. We then demonstrate that the
      FRET signal can be observed in live cells when the hybrid probes are transfected
      with the cSCK, and that the strength of the FRET signal is sequence specific and
      depends on the mRNA expression level.

PMID- 23538605
TI  - Alcohol Use, Problems, and the Course of Posttraumatic Stress Disorder: A
      Prospective Study of Female Crime Victims.
AB  - OBJECTIVE: This study examines whether alcohol use disorder status and
      consequences of drinking moderate the course of PTSD over the first 6 months
      following trauma exposure in a sample of female victims of interpersonal
      violence. METHODS: Female sexual and physical assault victims (n = 64) were
      recruited through police, hospital, and victim service agencies. Women completed
      structured clinical interviews and self-report measures within the first five
      weeks, three months, and six months post-trauma with 73% retention across all
      three time points (n = 47). Analyses were conducted using Hierarchical Linear
      Modeling using alcohol abuse/dependence, peak alcohol use, and consequences
      during the 30 days prior to assault as moderators of the course of PTSD over
      time. RESULTS: Women with alcohol use disorder at baseline had lower initial PTSD
      symptoms but also less symptom recovery over time than women without alcohol use
      disorder. This pattern of results was also found for those with high negative
      drinking consequences during the month prior to the assault. Baseline alcohol use
      was not found to significantly moderate PTSD course over the 6 months.
      CONCLUSIONS: Findings suggest that negative consequences associated with alcohol
      use may be a risk factor for PTSD. Incorporating assessment of drinking problems
      for women presenting early post-trauma may be useful for identifying PTSD risk.

PMID- 23538606
TI  - Plasma 8-isoprostane concentrations and adipogenic and adipokine gene expression
      patterns in subcutaneous and mesenteric adipose tissues of fattening Wagyu
      cattle.
AB  - We hypothesized that fattening Wagyu cattle fed conventional low-vitamin
      fattening diets are exposed to oxidative stress. In this experiment, we studied
      the plasma concentrations of 8-isoprostane and the fat depot-specific effects of
      the diet-induced adipogenic (C/EBPbeta, C/EBPdelta, C/EBPalpha and PPARgamma2)
      and adipokine (VEGF, FGF-2, leptin and adiponectin) gene expressions in fattening
      Wagyu steers. Animals were fed a high-vitamin (alpha-tocopherol and beta
      carotene) diet (HV) or a control diet (CT) during the fattening period (from 10
      to 30 months of age). The plasma concentrations of 8-isoprostane, a marker of
      oxidative stress, were significantly lower in the HV group than in the CT group.
      In mesenteric adipose tissue, the expressions of the adipogenic and adipokine
      genes in the HV group were significantly lower than those in the CT group. In
      contrast, there were no differences in the expression of the adipogenic and
      adipokine genes in subcutaneous adipose tissue between groups. These results
      suggest that higher intake of dietary alpha-tocopherol and beta-carotene affects
      the expression patterns of adipogenic and adipokine genes in a fat depot-specific
      manner with the reduction of plasma 8-isoprostane concentrations. 

PMID- 23538607
TI  - Detection and genotype of Encephalitozoon cuniculi DNA from urine and feces of
      pet rabbits in Japan.
AB  - A newly developed nested polymerase chain reaction (PCR) assay targeting the
      internal transcribed spacer (ITS) region of the ribosomal DNA was applied to
      detect and characterize Encephalitozoon cuniculi DNA from pet rabbits in Japan.
      The analysis was carried out using 257 urinary samples and 314 fecal samples
      collected from 307 pet rabbits in the age group of 1 month to 12 years from 30
      different prefectures of Japan and 107 fecal samples and 3 urinary samples
      collected from 1-month-old rabbits from 3 breeding facilities in Japan. We
      detected 840-bp amplicons in 20 urinary samples (7.78%) from the pet rabbits of
      the 13 prefectures and in 1 urinary (33.3%) and 6 fecal (5.6%) samples from the
      rabbits of the 2 breeding facilities. The sequences (803 bp) of the 27 amplicons
      had no variations and completely coincided with the sequence of E. cuniculi
      genotype I. To the best of our knowledge, this is the first report on the
      detection and genotype characterization of E. cuniculi DNA from pet rabbits in
      Japan. 

PMID- 23538608
TI  - An unusual temperature induced isostructural phase transition in a scheelite,
      Li(0.5)Ce(0.5)MoO4.
AB  - High resolution synchrotron X-ray diffraction, dielectric and Raman scattering
      study of a scheelite compound Li0.5Ce0.5MoO4 (LCM) revealed that it transforms to
      a self similar structure above 400  degrees C. The thermally induced
      isostructural phase transition (IPT), a phenomenon which has rarely been reported
      in the literature, is preceded by partial softening of the zone centre phonons
      followed by their hardening above the IPT transition temperature. The high
      temperature isostructural phase, which exhibits expanded lattice parameters and
      cell volume, nucleates and grows in the low temperature matrix over a very wide
      temperature range. Both the phases show nearly identical thermal expansion
      suggesting similarities in symmetry, unaltered coordination environments around
      the atoms across the transition.

PMID- 23538609
TI  - Serbian and Austrian alcohol-dependent patients: a comparison of two samples
      regarding therapeutically relevant clinical features.
AB  - AIMS: To support the Serbian Expert Board in setting up reimbursement for modern
      pharmacotherapeutic support, we compared a Serbian sample of alcohol-dependent
      patients with an Austrian sample, in order to detect differences that might
      inhibit the introduction of anti-craving medications in Serbia. METHODS: One
      hundred and twenty-seven (116 males) alcohol-dependent patients in Serbia and 136
      in Austria (78 males) were enrolled consecutively from January 2011 to March 2012
      and were assessed using the Lesch alcoholism typology instrument (LAT). RESULTS:
      Age of onset was slightly higher in the Austrian sample (28.5 vs. 30.0; P =
      0.10). The Serbian sample showed a higher rate of anxiety disorders than the
      Austrian sample (89.8 vs. 26.5%, P <= 0.0001). Suicidal tendencies, independent
      of alcohol intake or withdrawal syndrome, were higher in the Austrian sample (1.6
      vs. 13.2% P <= 0.0001). There was no difference between the two samples in Lesch
      Type IV (26 vs 28); there was a slight excess in the Serbian sample of Type I (15
      vs. 10). In Austria, significantly more Type II patients (32 vs. 52) had been
      included, while the Serbian sample comprised significantly more Type III
      patients. CONCLUSIONS: Austrian and Serbian patients are quite similar, without
      any showing any factor that would detract from the potential value of modern anti
      craving medications in Serbia. The differences in anxiety disorders might be due
      to the 1990s war and should be investigated further.

PMID- 23538610
TI  - Abstinence after first acute alcohol-associated pancreatitis protects against
      recurrent pancreatitis and minimizes the risk of pancreatic dysfunction.
AB  - AIMS: To determine the recurrence of pancreatitis and subsequent pancreatic
      function in patients who stop drinking after the first episode of alcohol
      associated pancreatitis. METHODS: Of a total of 118 patients suffering from their
      first alcohol-associated pancreatitis, 18 (all men, age median 47 (27-71) years)
      met the inclusion criterion for abstinence during follow-up. The criterion for
      abstinence was alcohol consumption <24 g per 2 months (self-estimated), which is
      in line with questionnaires eliciting alcohol consumption and dependency (Alcohol
      Use Disorders Identification Test < 8 and Short Alcohol Dependence Data < 9).
      Recurrent attacks of acute pancreatitis were studied. Smoking, body mass index
      and laboratory tests detecting heavy consumption of alcohol were recorded. Blood
      and faecal tests were studied to assess endocrine and exocrine pancreatic
      function. RESULTS: During a mean follow-up time of 5.15 (1.83-9.13) years and a
      total of 92.7 patient-years, there were no recurrent attacks of acute
      pancreatitis among the 18 abstainers. Two patients had diabetes prior to and one
      was diagnosed immediately after the first episode of acute pancreatitis. One
      patient had impaired glucose metabolism at 2 years. Two patients had low insulin
      secretion in glucagon-C-peptide test, one at 4 years and the other at 5 years.
      Only one patient (6%) maintained low elastase-1 activity during the abstinence
      follow-up. Of the 100 non-abstainers, 34% had at least one recurrence during the
      follow-up. CONCLUSION: Regardless of the mediator mechanisms of acute alcoholic
      pancreatitis, abstinence after the first episode protects against recurrent
      attacks. Pancreatic dysfunction is also rare among abstinent patients.

PMID- 23538611
TI  - Temperature affects methylation of the myogenin putative promoter, its expression
      and muscle cellularity in Senegalese sole larvae.
AB  - Myogenin (myog) encodes a highly conserved myogenic regulatory factor that is
      involved in terminal muscle differentiation. It has been shown in mammals that
      methylation of cytosines within the myog promoter plays a major role in
      regulating its transcription. In the present study, the Senegalese sole (Solea
      senegalensis) myog putative proximal promoter was identified and found to be
      highly conserved among teleosts. Therefore, it is plausible that it plays a
      similar role in controlling myog expression. Cytosine methylation of the myog
      promoter in skeletal muscle of Senegalese sole larvae undergoing metamorphosis
      was influenced by rearing temperature. A lower temperature (15  degrees C)
      significantly increased myog promoter methylation in skeletal muscle,
      particularly at specific CpG sites, relatively to higher rearing temperatures (18
      and 21  degrees C). Myog transcription was downregulated at 15  degrees C,
      whereas expression of dnmt1 and dnmt3b was upregulated, consistently with the
      higher myog methylation observed at this temperature. Rearing temperature also
      affected growth and fast muscle cellularity, producing larger fibers at 21
      degrees C. Taken together, our data provide the first evidence of an epigenetic
      mechanism that may be underlying the temperature-induced phenotypic plasticity of
      muscle growth in teleosts.

PMID- 23538612
TI  - Management of fingolimod-associated macular edema.

PMID- 23538613
TI  - Reply: To PMID 22262221.

PMID- 23538614
TI  - Analysis of the correlations of mucins, inflammatory markers, and clinical tests
      in dry eye.
AB  - PURPOSE: To investigate the expression of mucin and inflammatory factors in the
      conjunctival epithelium of subjects with dry eye and determine a correlation
      between clinical laboratory tests and subjective symptoms. METHODS: The ocular
      surface disease index questionnaire, corneal fluorescein staining, tear film
      breakup time, and Schirmer I tests were administered in 66 subjects. According to
      questionnaire scores, the subjects were divided into mild, moderate, and severe
      symptom groups. Then, the subjects were divided based on the clinical tests into
      negative and positive groups. Impression cytology specimens from all patients
      were immunolabeled with antibodies directed against human mucin 5AC (MUC5AC) and
      interleukin-6 (IL-6) and the staining density was measured. RESULTS: MUC5AC was
      lower in the severe symptom group compared with the mild and moderate symptom
      groups (P < 0.001, respectively). IL-6 was higher in the severe symptom group
      compared with the mild and moderate symptom groups (P < 0.001, respectively), and
      also in the moderate symptom group compared with the mild symptom group (P <
      0.001). A decrease of MUC5AC was found in the positive group compared with the
      negative group (P < 0.001). IL-6 was higher in the positive group compared with
      the negative group (P = 0.029). MUC5AC was negatively correlated with the ocular
      surface disease index scores (r = -0.697, P < 0.001), whereas IL-6 positively
      correlated the scores (r = 0.895, P < 0.001). There were weak correlations for
      MUC5AC and IL-6 with tear film breakup time (r = 0.158 and r = -0.195,
      respectively; P = 0.038 and P = 0.041, respectively), and no correlations with
      other clinical tests. CONCLUSIONS: Dry eye disease is associated with decreased
      levels of mucin and an overexpression of IL-6, which correlate to the symptomatic
      severity of disease.

PMID- 23538615
TI  - Gauging interest of the general public in laser-assisted in situ keratomileusis
      eye surgery.
AB  - PURPOSE: To assess interest among members of the general public in laser-assisted
      in situ keratomileusis (LASIK) surgery and how levels of interest in this
      procedure have changed over time in the United States and other countries.
      METHODS: Using the Google Trends Web site, we determined the weekly frequency of
      queries involving the term "LASIK" from January 1, 2007, through January 1, 2011,
      in the United States, United Kingdom, Canada, and India. We fit separate
      regression models for each of the countries to assess whether residents of these
      countries differed in their querying rates on specific dates and over time.
      Similar analyses were performed to compare 4 US states. Additional regression
      models compared general public interest in LASIK surgery before and after the
      release of a 2008 Food and Drug Administration report describing complaints
      associated with this procedure. RESULTS: During 2007 to 2011, the Google query
      rate for "LASIK" was highest among persons residing in India, followed by the
      United Kingdom, Canada, and the United States. During this time period, the query
      rate declined by 40% in the United States, 24% in India, and 22% in the United
      Kingdom, and it increased by 8% in Canada. In all 4 of the US states examined,
      the query rate declined-by 52% in Florida, 56% in New York, 54% in Texas, and 42%
      in California. Interest in LASIK declined further among US citizens after the
      Food and Drug Administration report release. CONCLUSIONS: Interest among the
      general public in LASIK surgery has been waning in recent years.

PMID- 23538616
TI  - Effect of postmortem interval on the graft endothelium during preservation and
      after transplantation for keratoconus.
AB  - PURPOSE: To investigate the effect of postmortem intervals and prognostic factors
      on endothelial cell density (ECD) of human donor corneas during preservation and
      at 1 and 3 years after transplantation in patients transplanted for keratoconus.
      METHODS: Two different studies were performed: (1) with 733 donor corneas
      selected for the preservation study and (2) 64 patients with keratoconus selected
      retrospectively from 2 hospital clinics. The corneas were evaluated on the basis
      of the ECD during preservation, study A, and at 1 and 3 years after
      transplantation, study B. The effect of >= 10 hours of postmortem interval on the
      percentage of corneal endothelial cell loss (ECL) was determined. RESULTS: The
      multiple regression showed no statistical significance (P = 0.827) of postmortem
      interval on ECL during preservation. However, for patients with keratoconus, the
      postmortem interval was statistically significant at both 1 year (P < 0.0001) and
      3 years after transplantation (P < 0.0001). CONCLUSIONS: The postmortem interval
      has no influence on the ECD during preservation. However, it has a statistically
      significant effect on the ECL after transplantation for patients transplanted for
      keratoconus, and therefore, it becomes eligible to be one of the potential
      factors affecting the ECD apart from surgical trauma.

PMID- 23538617
TI  - Cytomegalovirus-positive corneal stromal edema with keratic precipitates after
      penetrating keratoplasty: a case-control study.
AB  - PURPOSE: To identify differences between cytomegalovirus (CMV)-positive and CMV
      negative eyes presenting as suspected endothelial graft rejection after
      penetrating keratoplasty (PK). METHODS: A retrospective consecutive case-control
      series. Aqueous humor samples of all eyes with corneal stromal edema and keratic
      precipitates (KPs) after PK, seen at the Singapore National Eye Centre from 2007
      to 2010, were analyzed for CMV DNA by polymerase chain reaction. Their charts
      were reviewed for demographic data, medical and ocular history, best-corrected
      visual acuity, intraocular pressure, anterior segment clinical findings, and
      therapy. RESULTS: Of 11 eligible eyes (11 patients), 7 were CMV positive. All
      eyes were negative for herpes simplex virus and varicella zoster virus. The 2
      groups were similar in age, gender, and previous ocular surgery. The main
      differences were the presence of extensive heavily pigmented KPs, Descemet
      membrane folds, and the absence of vascularization of the donor in CMV-positive
      eyes (100% vs. 0%, P = 0.003, Fisher exact test). All the CMV-positive eyes were
      treated with ganciclovir (5 systemic, 2 topical), and the control eyes received
      immunosuppression. However, all the grafts failed. Best-corrected visual acuity
      at the last visit was worse than 20/400 in all except 1 control eye, which had a
      follow-up of 30 months. CONCLUSIONS: There is a high prevalence of CMV infection
      in eyes that develop corneal stromal edema with KPs after PK. Heavy endothelial
      pigmentation, Descemet membrane folds, and the absence of donor vascularization
      may aid in the diagnosis of CMV in the event that aqueous analysis is not
      possible.

PMID- 23538618
TI  - Morphological modification of the cornea after standard and transepithelial
      corneal cross-linking as imaged by anterior segment optical coherence tomography
      and laser scanning in vivo confocal microscopy.
AB  - PURPOSE: In vivo analysis of corneal modifications after traditional and
      transepithelial corneal cross-linking (CXL). METHODS: Forty eyes of 35 patients
      underwent traditional or transepithelial CXL; there was randomization of 20 eyes
      to each group. By means of in vivo confocal microscopy and anterior segment
      ocular coherence tomography, we evaluated corneal alterations at 1 week, 1 month,
      and 3, 6, and 12 months after the treatment. RESULTS: During follow-up, in vivo
      confocal microscopy showed a significant decrease in anterior keratocyte density
      (P = 0.001) and more evident stromal edema and keratocyte activation (P = 0.001)
      in the traditional group, whereas in the transepithelial group, no significant
      changes were observed (P > 0.05). Anterior segment ocular coherence tomography
      indicated the presence of hyperreflective stromal line significantly deeper and
      more persistent in the traditional group (P < 0.001). CONCLUSIONS: The
      preliminary results suggest that traditional CXL induced marked corneal
      modifications, which were poorly evident in the transepithelial group.

PMID- 23538619
TI  - Pterygium removal using a polyethylene glycol hydrogel adherent ocular bandage.
AB  - PURPOSE: To describe the result of using a polyethylene glycol hydrogel contact
      lens (ReSure; Ocular Therapeutix, Inc, Bedford, MA) as a protective bandage over
      denuded areas of Tenons after pterygium removal. METHODS: Five sequential
      patients underwent pterygium removal with a conjunctival autograft and painting
      of bare Tenons in the area of the graft retrieval with a biodegradable polymer,
      and these patients were followed for 1 year for immediate postoperative pain,
      epithelial healing, and long-term conjunctival scarring. RESULTS: All patients
      showed prolonged persistence of the polymer for up to 8 to 10 weeks with
      resultant increased conjunctival inflammation and scarring with no evidence of
      decreased postoperative pain. CONCLUSIONS: This hydrogel polymer seems to cause
      prolonged inflammation and resultant scarring when used over extended areas of
      Tenons, and it has no role in reducing pain after pterygium surgery.

PMID- 23538620
TI  - Donor tissue selection for anterior lamellar keratoplasty.
AB  - PURPOSE: To assess the influence of donor characteristics on the outcome of
      anterior lamellar keratoplasty (ALK) and to evaluate whether corneal donor tissue
      considered unsuitable for penetrating or posterior lamellar keratoplasty due to
      poor endothelial condition may be safely used for ALK. METHODS: Institutional
      setting. One hundred sixty-six consecutive ALK (166 patients) performed for
      optical indication in eyes with corneal diseases not involving the corneal
      endothelium. The main outcome measures were graft survival, early (0-12 months
      postoperatively) and late (after 12 months) annual endothelial cell loss, and
      postoperative logarithm of the minimum angle of resolution visual acuity.
      RESULTS: The average and extreme values of donor tissue characteristics were:
      donor age, 70.6 years (range, 28-88 years); organ culture time, 20.9 days (range,
      12-35 days); graft endothelial cell density before transplantation, 2047 cells
      per millimeters (range, 100-3300 cells/mm2); and deswelling time, 2.0 days
      (range, 1-4 days). The average follow-up time of patients was 48.1 +/- 24.8
      months (mean +/- SD). None of the donor characteristics significantly influenced
      graft survival or postoperative endothelial cell loss (early and late phase).
      Donor age >80 years was associated with lower postoperative visual acuity at all
      postoperative points in time (P < 0.05). At 3 years, the mean logarithm of the
      minimum angle of resolution visual acuity was 0.44 (20/55) for grafts from donors
      older than 80 years and 0.25 (20/35) for younger donors. This result was shown to
      be significant both in univariate and in multivariate analysis. CONCLUSIONS:
      Grafts from elderly donors should be discarded before ALK. Conversely, donor
      tissue with poor endothelial cell density (<2000 cells/mm2) is suitable for ALK.

PMID- 23538621
TI  - Effects of oral mucolytics on tear film and ocular surface.
AB  - PURPOSE: To evaluate the effects of oral ambroxol on tear film and ocular
      surface. METHODS: Twenty healthy male subjects with no ocular disease were
      recruited. Subjects were divided into 2 groups: a control group and an ambroxol
      group. Ambroxol hydrochloride was administered orally to the ambroxol group. The
      tear film and ocular surface were evaluated at baseline (10 AM), 12 PM, 6 PM, and
      10 AM the next day. Visual analog pain scale, tear film break-up time,
      fluorescein corneal staining, Schirmer test, tear osmolality, and fluorescein
      clearance test were measured. RESULTS: The mean visual analog pain scale score
      increased at 6 PM and 10 AM the next day in the ambroxol group (P = 0.007 and P =
      0.018, respectively). The tear film break-up time did not show any significant
      change in the control group and shortened at 6 PM in the ambroxol group (P =
      0.011). The fluorescein corneal staining scores increased at 6 PM in both groups
      (P = 0.007 and P = 0.004, respectively), and they were higher in the ambroxol
      group compared with control group at 10 AM the next day (P = 0.035). The mean
      tear secretion did not show a significant change in the control group and
      increased at 10 AM the next day in the ambroxol group (P = 0.022). In both
      groups, the tear osmolality increased at 6 PM (P = 0.009 and P = 0.005,
      respectively), but the tear osmolality in the ambroxol group was higher compared
      with control group at 6 PM (P = 0.043). CONCLUSIONS: Oral ambroxol may disturb
      tear film and ocular surfaces by attenuating the mucin layer of the tear film.

PMID- 23538622
TI  - Dry eye in patients with fibromyalgia and its relevance to functional and
      emotional status.
AB  - PURPOSE: To evaluate dry eye in patients with fibromyalgia (FM). METHODS: Fifty
      three FM patients and 53 age and sex well-matched controls were included in this
      study. Visual analog scale (VAS), number of tender points, FM impact
      questionnaire (FIQ), Beck depression scale (BDS), Ocular Surface Disease Index
      (OSDI), the tear break-up time (TBUT), Schirmer test, and tear osmolarity (TO)
      were assessed. RESULTS: The OSDI, TBUT, Schirmer test, and TO scores of the FM
      and control groups were significantly different (P < 0.05). The OSDI, TBUT,
      Schirmer test, and TO were higher in FM with high FIQ, and TBUT and TO were
      higher in FM with high BDS. In FM patients, Schirmer test was correlated with the
      VAS (r = -0.429, P = 0.001), BDS (r = -0.277, P = 0.044), and FIQ (r = -0.382, P
      = 0.005), and the TBUT was correlated with the VAS (r = -0.537, P < 0.001), BDS
      (r = -0.350, P = 0.010), and FIQ (r = -0.456, P = 0.001). In addition, TO was
      significantly correlated with the VAS (r = 0.681, P < 0.001), BDS (r = 0.661, P <
      0.001), and FIQ (r = 0.842, P < 0.001). However, no significant correlation
      existed between the OSDI and the VAS, BDS, or FIQ. CONCLUSIONS: We have revealed
      an association between FM disease activity and dry eye severity. The
      consideration of this relation will be useful in the treatment of FM with
      deteriorated clinical status.

PMID- 23538623
TI  - Anterior segment OCT and confocal microscopy findings in atypical corneal
      intraepithelial neoplasia.
AB  - PURPOSE: To report a case of biopsy-proven corneal intraepithelial neoplasia
      (CIN) diagnosed and followed clinically using high-resolution anterior segment
      optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM).
      METHODS: Observational case report. RESULTS: A 57-year-old man presented with
      decreased vision in the right eye for 2 months before presentation. His best
      corrected visual acuity was 20/70 in the affected eye, and the slit-lamp
      examination revealed superficial opacification of the anterior cornea originating
      from the temporal limbus with a "leopard-spot" pattern more centrally. The lesion
      was excised at his 2-month follow-up, and the histological examination revealed
      squamous dysplasia consistent with CIN. Visual acuity improved, and the slit-lamp
      examination revealed barely visible residual disease at the temporal limbus.
      However, AS-OCT showed a thicker and highly reflective epithelial layer near the
      temporal limbus, similar to initial presentation, highlighting this residual
      disease. IVCM demonstrated dysplastic cells consistent with residual disease.
      Therefore, we treated the patient with topical interferon alpha-2b (1 million
      IU/mL) 4 times daily in the affected eye. At 3-month follow-up, the patient's
      best-corrected visual acuity was 20/20 in the affected eye with persistent but
      improved residual disease adjacent to the temporal limbus. In the mid-periphery
      of the inferonasal cornea, focal areas of iatrogenic linear scarring were
      confirmed to be limited to the anterior stroma by AS-OCT and IVCM at 6-month
      follow-up. CONCLUSIONS: AS-OCT and IVCM are noninvasive techniques that can be
      used to diagnose and aid in the management of CIN, which may present as
      subclinical disease through slit-lamp biomicroscopy alone.

PMID- 23538624
TI  - Oxidative stress in experimental rodent corneas infected with aflatoxigenic and
      nonaflatoxigenic Aspergillus flavus.
AB  - PURPOSE: To seek a possible association between aflatoxigenicity and oxidative
      stress in keratitis caused by Aspergillus flavus in an experimental rodent model.
      METHODS: Wistar rats were divided into 3 groups of 6 each. Group 1 served as mock
      inoculated controls. Experimental fungal keratitis was induced in group 2 and
      group 3 rats using aflatoxigenic and nonaflatoxigenic A. flavus conidial
      suspensions, respectively, and clinical features were scored for 5 days after
      inoculation. At this time, animals were killed, and test corneas were excised and
      examined histologically. Expression of IL-1beta and TNF-alpha genes was sought in
      excised corneas. Levels of malondialdehyde (MDA) and reduced glutathione (GSH)
      and activities of key antioxidant enzymes were measured in excised corneas and
      fungal mycelial homogenates. Antioxidant enzyme isoforms were sought in mycelial
      homogenates by native polyacrylamide gel electrophoresis. RESULTS: Mean levels of
      MDA and GSH and mean activities of catalase, superoxide dismutase, and
      glutathione peroxidase were significantly (P < 0.05) higher in a mycelial
      homogenate of aflatoxigenic A. flavus than in the nonaflatoxigenic mycelial
      homogenate. Increased numbers of well-stained isoforms were detected in
      aflatoxigenic mycelial homogenates. Significantly (P < 0.05) higher expression
      profiles of IL-1beta and TNF-alpha genes, MDA and GSH levels, and antioxidant
      enzyme activities were noted in group 2 rat corneas than in group 3 rat corneas.
      Clinical and histological scores suggested a more severe keratitis in group 2 rat
      corneas than in group 1 and group 3 rat corneas. CONCLUSIONS: Aflatoxigenicity is
      associated with more intense oxidative stress in experimental A. flavus
      keratitis.

PMID- 23538625
TI  - The Boston keratoprosthesis type I in mucous membrane pemphigoid.
AB  - PURPOSE: To evaluate the use of the Boston keratoprosthesis type I implantation
      in patients with mucous membrane pemphigoid (MMP). METHODS: Retrospective review
      of 8 eyes of 8 patients with severe ocular surface disease and corneal blindness
      as a result of MMP who underwent Boston keratoprosthesis type I implantation at
      the Massachusetts Eye and Ear Infirmary from January 1, 2000, through December
      31, 2009. The main outcome measures were best-corrected visual acuity,
      keratoprosthesis retention, and postoperative complications. RESULTS: The mean
      age of patients was 71.3 years (range, 55-94 years), and the mean duration of
      their disease preoperatively was 6.1 years (range, 1.7-11.4 years). Visual acuity
      after the surgery improved to 20/200 or better in 6 eyes (75%) and to 20/40 or
      better in 3 eyes (37.5%). Only 1 of 6 eyes (16.7%) was able to maintain visual
      acuity of 20/200 or better over a mean follow-up period of 3.2 years. Five of the
      8 Boston keratoprosthesis type I devices (62.5%) extruded or had to be replaced
      during a mean follow-up time of 1.7 +/- 1.7 years. Loss of vision to worse than
      20/200 during the follow-up period occurred because of keratoprosthesis type I
      extrusion, end-stage glaucoma, and retinal or choroidal detachment. CONCLUSIONS:
      The clinical outcomes of Boston keratoprosthesis type I implantation in MMP are
      guarded and, as judged from the literature, less favorable than those with the
      Boston keratoprosthesis type II for the same disease.

PMID- 23538626
TI  - Evaluation of the corneal collagen cross-linking demarcation line profile using
      anterior segment optical coherence tomography.
AB  - PURPOSE: To evaluate the depth of the stromal demarcation line after corneal
      collagen cross-linking (CXL) using anterior segment optical coherence tomography.
      METHODS: In this prospective, interventional case series, 23 patients (27 eyes)
      with progressive keratoconus were enrolled. All patients underwent uneventful CXL
      treatment. Corneal stromal demarcation line depth was measured centrally, 3 mm
      temporally, and 3 mm nasally by 2 independent observers using anterior segment
      optical coherence tomography at 1 month postoperatively in all patients. RESULTS:
      Mean depth of the corneal stromal demarcation line measured by the first observer
      was 310.67 +/- 31.04 MUm (range, 258-364 MUm) centrally, 212.07 +/- 24.5 MUm
      (range, 178-279 MUm) nasally, and 218.04 +/- 21.91 MUm (range, 191-261 MUm)
      temporally. Mean depth of the corneal stromal demarcation line measured by the
      second observer was 308.78 +/- 29 MUm (range, 262-381 MUm) centrally, 211.04 +/-
      23.93 MUm (range, 180-277 MUm) nasally, and 217.22 +/- 25.51 MUm (range, 179-271
      MUm) temporally. There was a statistically significant difference (P < 0.001)
      between central and both nasal and temporal depths of the corneal stromal
      demarcation line (paired samples t test) for both observers. There was no
      statistically significant difference between nasal and temporal corneal stromal
      demarcation line depths (paired samples t test, P > 0.05) for each observer.
      CONCLUSIONS: Mean depth of the corneal stromal demarcation line after CXL
      treatment is greater centrally in comparison with nasal and temporal depths.

PMID- 23538627
TI  - Standard terminology and labeling of ocular tissue for transplantation.
AB  - PURPOSE: To develop an internationally agreed terminology for describing ocular
      tissue grafts to improve the accuracy and reliability of information transfer, to
      enhance tissue traceability, and to facilitate the gathering of comparative
      global activity data, including denominator data for use in biovigilance
      analyses. METHODS: ICCBBA, the international standards organization for
      terminology, coding, and labeling of blood, cells, and tissues, approached the
      major Eye Bank Associations to form an expert advisory group. The group met by
      regular conference calls to develop a standard terminology, which was released
      for public consultation and amended accordingly. RESULTS: The terminology uses
      broad definitions (Classes) with modifying characteristics (Attributes) to define
      each ocular tissue product. The terminology may be used within the ISBT 128
      system to label tissue products with standardized bar codes enabling the
      electronic capture of critical data in the collection, processing, and
      distribution of tissues. Guidance on coding and labeling has also been developed.
      CONCLUSIONS: The development of a standard terminology for ocular tissue marks an
      important step for improving traceability and reducing the risk of mistakes due
      to transcription errors. ISBT 128 computer codes have been assigned and may now
      be used to label ocular tissues. Eye banks are encouraged to adopt this standard
      terminology and move toward full implementation of ISBT 128 nomenclature, coding,
      and labeling.

PMID- 23538628
TI  - Intraocular pressure measured with Goldmann, noncontact, Schiotz, and dynamic
      contour tonometry after DSEK.
AB  - PURPOSE: To compare intraocular pressure (IOP) measurements with various
      tonometers after Descemet stripping with endothelial keratoplasty (DSEK) and to
      measure the change in IOP during the follow-up period. METHODS: A total of 28
      eyes of 28 patients having undergone DSEK for bullous keratopathy by a single
      surgeon from June 2008 to November 2011 were enrolled in this study. IOP values,
      which were measured with Goldmann applanation tonometry (GAT), noncontact
      tonometry (NCT), Schiotz indentation tonometry (SIT), and dynamic contour
      tonometry, and central corneal thickness values were reviewed and analyzed up to
      3 years after DSEK (range, 1 months-3 years). RESULTS: Different tonometers
      measured the IOP after DSEK differently. NCT showed the lowest IOP values,
      although GAT and NCT showed the smallest intertonometry difference. SIT showed
      extreme variation in IOP measurements. The dynamic contour tonometry values were
      higher than those of NCT or GAT. Central corneal thickness did not correlate with
      any of the IOP measurements. Only 2 episodes of IOP elevation greater than 30 mm
      Hg were detected. CONCLUSIONS: IOP measured with NCT or GAT may be lower than the
      real IOP after DSEK. SIT is not a reliable tonometry measurement after DSEK.
      Additional IOP measurements using different methods and consideration of other
      clinical signs may be the best method for ocular evaluation after DSEK.

PMID- 23538629
TI  - Outcomes of treatment of fungal keratitis at the University of Iowa Hospitals and
      Clinics: a 10-year retrospective analysis.
AB  - PURPOSE: To evaluate the outcomes of medical and surgical management of fungal
      keratitis at a tertiary care eye center. METHODS: A retrospective review was
      performed of the medical records of all patients with a diagnosis of
      microbiologically or histopathologically confirmed fungal keratitis at the
      University of Iowa Hospitals and Clinics from July 1, 2001, through June 30,
      2011. The main outcome measure was a microbiological cure with either medical
      therapy alone or medical therapy combined with therapeutic keratoplasty (TKP).
      The secondary outcome measures were graft survival of the TKPs and subsequent
      optical keratoplasties (OKPs) and visual outcome. RESULTS: Seventy-three eyes met
      the inclusion criteria. A microbiological cure was achieved in 72 eyes (98.6%).
      Forty-one eyes (56.2%) were treated with medical therapy alone, and 32 (43.8%)
      eyes required 1 TKP (29 eyes) or 2 TKPs (3 eyes). Among the 32 eyes treated with
      TKP, 17 (53.1%) maintained a clear graft. Among 15 eyes with failed grafts, 12
      eyes ultimately achieved clear grafts after a total of 19 OKP procedures. Among
      41 eyes treated with medical therapy alone, all 3 eyes treated with OKP remained
      clear. The final median best-corrected visual acuity was 20/30 in the medical
      therapy group and 20/40 in the TKP group. CONCLUSIONS: A high microbiological
      cure rate can be achieved in eyes with fungal keratitis; however, TKP is often
      needed to achieve this objective. A good final visual outcome can be achieved in
      most cases, but multiple keratoplasty procedures may be required.

PMID- 23538630
TI  - Long-term corneal clarity after spontaneous repair of an iatrogenic
      descemetorhexis in a patient with Fuchs dystrophy.
AB  - PURPOSE: To report a case of long-term corneal clarity after spontaneous
      resolution of corneal edema associated with iatrogenic endothelial trauma in a
      patient with Fuchs dystrophy. METHODS: Retrospective case report. RESULTS: An 84
      year-old woman with Fuchs dystrophy experienced an iatrogenic descemetorhexis
      during complicated phacoemulsification. Despite marked early postoperative
      corneal edema, she experienced spontaneous clearing of her cornea within 4 months
      with eventual reendothelialization of the central defect. She maintained
      excellent visual acuity for 16 years with no evidence of recurrent corneal edema.
      CONCLUSIONS: Self-repair of a descemetorhexis and long-term corneal clarity may
      occur in eyes with underlying endothelial dystrophy.

PMID- 23538631
TI  - Long-term results of keratoplasty in patients with herpes zoster ophthalmicus.
AB  - PURPOSE: To report the long-term results of keratoplasty in patients with herpes
      zoster ophthalmicus (HZO). METHODS: All 14 patients underwent keratoplasty for a
      corneal scar or a perforated corneal ulcer due to HZO at the Wills Eye Institute
      from January 1999 to August 2011. RESULTS: We performed 9 penetrating
      keratoplasties and 1 deep anterior lamellar keratoplasty for corneal scarring,
      and 4 tectonic penetrating keratoplasties for perforated corneal ulceration due
      to HZO. Eight of the 14 eyes had a temporary tarsorrhaphy concurrent with graft.
      Postoperative follow-up time ranged from 12 to 132 months (mean 64 +/- 38).
      Postoperatively, the most common complications were dense superficial punctate
      keratopathy and severe dry eye because of neuropathic keratopathy in 8 eyes,
      graft rejection in 5 eyes, and secondary glaucoma in 4 eyes. All grafts were
      clear, and best spectacle-corrected visual acuity was 20/40 or better in 6 eyes
      (42.8%) and 20/100 or better in 9 eyes at their final evaluation (64.2%).
      CONCLUSIONS: Although the sample size is small, we demonstrate that very good
      visual results in long-term follow-up can be achieved when keratoplasty is
      performed in patients with herpes zoster virus keratopathy. We believe that
      longer quiescent waiting period between active herpes zoster ocular involvement
      and keratoplasty may promote better visual results.

PMID- 23538632
TI  - Remote manipulation of posterior lamellar corneal grafts using a magnetic field.
AB  - PURPOSE: In posterior lamellar keratoplasty procedures such as Descemet stripping
      endothelial keratoplasty and Descemet membrane endothelial keratoplasty, the
      lamellar graft is manipulated directly or by injecting an air bubble. This
      preliminary study sought to evaluate the feasibility of guiding lamellar corneal
      grafts by generating a magnetic field. METHODS: Rabbit and porcine Descemet
      stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty
      grafts were manually produced and immersed in a ferromagnetic solution containing
      nanomagnetic particles conjugated to streptavidin or in gadoteric acid. For the
      feasibility study, grafts were transferred to an artificial anterior chamber or
      plastic test tube and a magnetic field was generated with a handheld NdFeB disc
      magnet. The presence and the sustainability of graft motion were documented under
      various conditions. For the semiquantitative study, whole or partial grafts were
      transferred to a plastic test tube after immersion, and the amount of tissue
      retraction induced by the remote magnet was graded. RESULTS: The grafts were
      successfully manipulated in all directions by the magnet, from a distance of up
      to 7 mm. They remained ferromagnetic more than 24 hours after immersion in the
      ferromagnetic solutions. The degree of retraction was affected by graft size,
      immersion time, time from immersion, and immersion solution. CONCLUSIONS:
      Posterior lamellar corneal grafts may be made ferromagnetic and remotely
      manipulated by creation of a magnetic field. The ferromagnetic properties are
      adjustable. This technique holds promise in attaching and repositioning grafts
      during keratoplasty. Further research is needed to assess the possible effects of
      ferromagnetic solutions on corneal endothelial cells and on lamellar graft
      clarity.

PMID- 23538633
TI  - Retrocorneal membrane formation after Baerveldt shunt implantation for
      iridocorneal endothelial syndrome.
AB  - PURPOSE: Retrocorneal membranes can occur after trauma or surgery and remain as a
      therapeutic problem in graft failure after penetrating keratoplasty. We report
      for the first time the finding of a retrocorneal membrane in Descemet stripping
      automated endothelial keratoplasty (DSAEK) in a young woman who underwent
      Baerveldt shunt implantation for iridocorneal endothelial (ICE) syndrome.
      METHODS: Clinical examination, preoperative and postoperative slit lamp-adapted
      optical coherence tomography of the anterior segment, and immunohistochemical
      staining and electron microscopic analysis of the stripped Descemet membrane were
      performed. RESULTS: A 25-year-old woman presented with decline of visual acuity
      because of the formation of a retrocorneal membrane after Baerveldt shunt
      implantation for ICE syndrome. Visual acuity improved after DSAEK from 20/200 to
      20/63, whereas intraocular pressure did not change in the 6-month postoperative
      follow-up. Histological and ultrastructural analysis showed a massive
      retrocorneal membrane. Immunohistopositivity for alpha-smooth muscle actin,
      cytokeratin 7, and pan-cytokeratin suggests a metaplastic endothelial origin of
      this membrane. CONCLUSIONS: The exact origin of the retrocorneal membrane found
      in this case in ICE syndrome after Baerveldt shunt implantation cannot be
      clarified, but DSAEK is an effective treatment to improve visual acuity in this
      situation.

PMID- 23538634
TI  - Subconjunctival bevacizumab injection for ocular surface squamous neoplasia.
AB  - PURPOSE: To determine the efficacy and safety of perilesional/subconjunctival
      bevacizumab injections in the management of ocular surface squamous neoplasia
      (OSSN). METHODS: Ten eyes of 10 patients with an OSSN diagnosis confirmed by
      impression cytology received 2 perilesional/subconjunctival injections of
      bevacizumab at a 2-week interval. Patients were evaluated for 3 months, during
      which time, changes in the lesions were documented using digital photography.
      After this period, excisional biopsy of the remaining tumor and cryotherapy of
      the conjunctival borders were performed if deemed necessary. RESULTS: The mean
      age of the patients was 65 +/- 12 years (+/- SD). All of the tumors were nasal in
      origin and had varying degrees of vascularization. The mean lesion area before
      treatment was 16 +/- 6.9 mm2. Two weeks after the first injection, the mean
      reduction observed in the tumor area was 25% +/- 5.65% and ranged from 17% to 33%
      (P = 0.001). Two weeks after the second injection, the mean tumor area was
      further decreased (42% +/- 33%, ranging from 15% to 100%, P = 0.049). Corneal
      extension of the tumor was not affected significantly in 8 of the eyes with
      concomitant conjunctival and corneal involvement. Complete disappearance of the
      tumor was demonstrated by impression cytology and occurred in 2 cases involving
      lesions clinically confined to the conjunctiva. No systemic or ocular side
      effects occurred during the study period. CONCLUSIONS:
      Perilesional/subconjunctival injections of bevacizumab decrease the size and
      vascularity of OSSN and may be curative in lesions limited to the conjunctiva.
      However, this treatment has no significant effect on the corneal extension of
      OSSN.

PMID- 23538635
TI  - Genotype-phenotype analysis of Bietti crystalline dystrophy in a family with the
      CYP4V2 Ile111Thr mutation.
AB  - PURPOSE: The purposes of this study were to evaluate the genotypic and phenotypic
      correlations of Bietti crystalline dystrophy and to investigate the utility of in
      vivo corneal confocal microscopy in diagnosing this disorder. METHODS: A Spanish
      woman (proband) with a clinical diagnosis of Bietti crystalline dystrophy and 7
      members of her family were recruited prospectively for complete clinical
      ophthalmic examination and genetic study. The medical records of an additional
      family member were reviewed retrospectively. Genomic DNA was obtained from blood
      samples, and 11 exons of the CYP4V2 gene were screened for mutations by
      polymerase chain reaction DNA sequencing. RESULTS: Clinical examination revealed
      an atypical pattern of corneal dystrophy with central and paracentral
      distribution not only in the proband but also in 2 elderly heterozygous carriers.
      Corneal deposits were observed by slit-lamp examination and in vivo corneal
      confocal microscopy. Genetic analysis revealed the homozygous CYP4V2 Ile111Thr
      mutation in the proband and identified 5 heterozygous carriers. CONCLUSIONS: The
      authors identified a case of Bietti crystalline dystrophy with central and
      paracentral keratopathy and the molecular analysis of the causative gene in a
      Spanish family. Data suggest a dose-dependent phenotype ranging from subclinical
      corneal changes in subjects carrying 1 mutant Ile111Thr CYP4V2 allele to the
      complete manifestation of the disease in homozygous subjects. In vivo corneal
      confocal microscopy is a useful technique in the diagnosis of this disorder.

PMID- 23538636
TI  - Evaluating DSAEK graft deturgescence in preservation medium after microkeratome
      cut with optical coherence tomography.
AB  - PURPOSE: To evaluate the Descemet stripping automated endothelial keratoplasty
      (DSAEK) graft deturgescence in preservation medium after microkeratome cut using
      Fourier domain optical coherence tomography. METHODS: The central and peripheral
      thickness of DSAEK grafts was measured by Fourier domain optical coherence
      tomography immediately after microkeratome cuts and 1, 2, 3, and 4 hours
      afterward. All measurements were taken when the grafts were stored in 4 degrees C
      preservation medium. The hourly change in central graft thickness and graft shape
      (peripheral graft thicknes - central graft thickness) was calculated and tracked
      over time. RESULTS: Five DSAEK grafts were measured. The average central graft
      thickness was 188.7 +/- 44.4 MUm (range, 146-255 um) immediately after
      microkeratome cuts. The average central graft thickness was 147.5 +/- 33.0 MUm
      (range, 116-190 um) after 4 hours in preservation medium (P < 0.001). The average
      hourly change in central graft thickness was -30.5 MUm (P = 0.0051), -8.6 MUm (P
      = 0.055), -2.0 MUm (P = 0.42), and 0.0 MUm (P = 0.93) at 1, 2, 3, and 4 hours,
      respectively, after microkeratome cuts. The average hourly change in graft shape
      was insignificant. CONCLUSIONS: DSAEK grafts become thinner after microkeratome
      cut and stabilize at approximately 2 hours. Therefore, DSAEK graft thickness
      should be measured at 1.5 to 3 hours after microkeratome cut.

PMID- 23538637
TI  - Relationships between the built environment and walking and weight status among
      older women in three U.S. States.
AB  - There are few studies of built environment associations with physical activity
      and weight status among older women in large geographic areas that use individual
      residential buffers to define environmental exposures. Among 23,434 women (70.0
      +/- 6.9 yr; range = 57-85) in 3 states, relationships between objective built
      environment variables and meeting physical activity recommendations via walking
      and weight status were examined. Differences in associations by population
      density and state were explored in stratified models. Population density (odds
      ratio [OR] =1.04 [1.02, 1.07]), intersection density (ORs = 1.18-1.28), and
      facility density (ORs = 1.01-1.53) were positively associated with walking.
      Density of physical activity facilities was inversely associated with
      overweight/obesity (OR = 0.69 [0.49, 0.96]). The strongest associations between
      facility density variables and both outcomes were found among women from higher
      population density areas. There was no clear pattern of differences in
      associations across states. Among older women, relationships between accessible
      facilities and walking may be most important in more densely populated settings. 

PMID- 23538639
TI  - Antimicrobial activity of calcium hydroxide and chlorhexidine on intratubular
      Candida albicans.
AB  - This study investigated the efficacy of calcium hydroxide and chlorhexidine gel
      for the elimination of intratubular Candida albicans (C. albicans). Human single
      rooted teeth contaminated with C. albicans were treated with calcium hydroxide,
      2% chlorhexidine gel, calcium hydroxide plus 2% chlorhexidine gel, or saline
      (0.9% sodium chloride) as a positive control. The samples obtained at depths of 0
      100 and 100-200 um from the root canal system were analyzed for C. albicans load
      by counting the number of colony forming units and for the percentage of viable
      C. albicans using fluorescence microscopy. First, the antimicrobial activity of
      calcium hydroxide and the 2% chlorhexidine gel was evaluated by counting the
      number of colony forming units. After 14 days of intracanal medication, there was
      a significant decrease in the number of C. albicans colony forming units at a
      depth of 0-100 um with chlorhexidine treatment either with or without calcium
      hydroxide compared with the calcium hydroxide only treatment. However, there were
      no differences in the number of colony forming units at the 100-200 um depth for
      any of the medications investigated. C. albicans viability was also evaluated by
      vital staining techniques and fluorescence microscopy analysis. Antifungal
      activity against C. albicans significantly increased at both depths in the
      chlorhexidine groups with and without calcium hydroxide compared with the groups
      treated with calcium hydroxide only. Treatments with only chlorhexidine or
      chlorhexidine in combination with calcium hydroxide were effective for
      elimination of C. albicans.

PMID- 23538640
TI  - The similarity between human embryonic stem cell-derived epithelial cells and
      ameloblast-lineage cells.
AB  - This study aimed to compare epithelial cells derived from human embryonic stem
      cells (hESCs) to human ameloblast-lineage cells (ALCs), as a way to determine
      their potential use as a cell source for ameloblast regeneration. Induced by
      various concentrations of bone morphogenetic protein 4 (BMP4), retinoic acid (RA)
      and lithium chloride (LiCl) for 7 days, hESCs adopted cobble-stone epithelial
      phenotype (hESC-derived epithelial cells (ES-ECs)) and expressed cytokeratin 14.
      Compared with ALCs and oral epithelial cells (OE), ES-ECs expressed amelogenesis
      associated genes similar to ALCs. ES-ECs were compared with human fetal skin
      epithelium, human fetal oral buccal mucosal epithelial cells and human ALCs for
      their expression pattern of cytokeratins as well. ALCs had relatively high
      expression levels of cytokeratin 76, which was also found to be upregulated in ES
      ECs. Based on the present study, with the similarity of gene expression with
      ALCs, ES-ECs are a promising potential cell source for regeneration, which are
      not available in erupted human teeth for regeneration of enamel.

PMID- 23538641
TI  - Characterization of oral bacterial diversity of irradiated patients by high
      throughput sequencing.
AB  - The objective of this study was to investigate the compositional profiles and
      microbial shifts of oral microbiota during head-and-neck radiotherapy.
      Bioinformatic analysis based on 16S rRNA gene pyrosequencing was performed to
      assess the diversity and variation of oral microbiota of irradiated patients.
      Eight patients with head and neck cancers were involved in this study. For each
      patient, supragingival plaque samples were collected at seven time points before
      and during radiotherapy. A total of 147,232 qualified sequences were obtained
      through pyrosequencing and bioinformatic analysis, representing 3,460 species
      level operational taxonomic units (OTUs) and 140 genus level taxa. Temporal
      variations were observed across different time points and supported by cluster
      analysis based on weighted UniFrac metrics. Moreover, the low evenness of oral
      microbial communities in relative abundance was revealed by Lorenz curves. This
      study contributed to a better understanding of the detailed characterization of
      oral bacterial diversity of irradiated patients.

PMID- 23538642
TI  - Conjunctival papilloma: features and outcomes based on age at initial
      examination.
AB  - IMPORTANCE: Conjunctival papilloma is a benign epithelial tumor occurring in both
      children and adults with varying clinical features and outcomes. In this article,
      we describe our experience regarding the difference in the clinical features and
      outcomes of conjunctival papilloma based on age at initial examination.
      OBJECTIVE: To evaluate the clinical features, treatment, and outcomes in patients
      with conjunctival papilloma based on age at initial examination. DESIGN:
      Retrospective study. SETTING: Ocular Oncology Service, Wills Eye Hospital,
      Philadelphia, Pennsylvania. PARTICIPANTS: Ten children and adolescents (aged <=20
      years) and 63 adults (aged >20 years) with conjunctival papilloma. INTERVENTIONS:
      Excisional biopsy, cryotherapy, oral cimetidine, topical or injection interferon
      alfa-2b, and photodynamic therapy. MAIN OUTCOME MEASURE: Tumor response. RESULTS:
      A comparison of conjunctival papillomas between age groups revealed significant
      differences in the mean number of tumors per eye (children and adolescents vs
      adults, 2 vs 1; P = .05), tumor basal dimension (8 vs 6 mm; P = .05), and
      associated feeder vessels (20% vs 47%; P = .05). Primary treatment included sole
      treatment with oral cimetidine (15% vs 5%), topical interferon alfa-2b (0% vs
      1%), cryotherapy (0% vs 3%), photodynamic therapy (0% vs 1%), excisional biopsy
      and cryotherapy (38% vs 65%), excisional biopsy and cryotherapy with adjuvant
      oral cimetidine (8% vs 9%), and excisional biopsy and cryotherapy with adjuvant
      topical or injection interferon alfa-2b (38% vs 15%). Significant differences in
      age groups in treatment outcome during the follow-up period (mean, 24 vs 38
      months) included complete regression with single treatment (38% vs 95%; P < .01)
      and tumor recurrence (15% vs 1%; P = .05). CONCLUSIONS AND RELEVANCE:
      Conjunctival papillomas are larger and more likely to be multiple in children and
      adolescents than in adults. Excisional biopsy and cryotherapy with or without
      adjuvant oral cimetidine and/or topical interferon alfa-2b provide satisfactory
      tumor control. Papilloma recurrence is more common in children and adolescents
      than in adults.

PMID- 23538643
TI  - Treatment outcome in adults with chronic fatigue syndrome: a prospective study in
      England based on the CFS/ME National Outcomes Database.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is relatively common and disabling.
      Over 8000 patients attend adult services each year, yet little is known about the
      outcome of patients attending NHS services. AIM: Investigate the outcome of
      patients with CFS and what factors predict outcome. DESIGN: Longitudinal patient
      cohort. METHODS: We used data from six CFS/ME (myalgic encephalomyelitis)
      specialist services to measure changes in fatigue (Chalder Fatigue Scale),
      physical function (SF-36), anxiety and depression (Hospital Anxiety and
      Depression Scale) and pain (visual analogue pain rating scale) between clinical
      assessment and 8-20 months of follow-up. We used multivariable linear regression
      to investigate baseline factors associated with outcomes at follow-up. RESULTS:
      Baseline data obtained at clinical assessment were available for 1643 patients,
      of whom 834 (51%) had complete follow-up data. There were improvements in fatigue
      [mean difference from assessment to outcome: -6.8; 95% confidence interval (CI) 
      7.4 to -6.2; P < 0.001]; physical function (4.4; 95% CI 3.0-5.8; P < 0.001),
      anxiety (-0.6; 95% CI -0.9 to -0.3; P < 0.001), depression (-1.6; 95% CI -1.9 to 
      1.4; P < 0.001) and pain (-5.3; 95% CI -7.0 to -3.6; P < 0.001). Worse fatigue,
      physical function and pain at clinical assessment predicted a worse outcome for
      fatigue at follow-up. Older age, increased pain and physical function at
      assessment were associated with poorer physical function at follow-up.
      CONCLUSION: Patients who attend NHS specialist CFS/ME services can expect similar
      improvements in fatigue, anxiety and depression to participants receiving
      cognitive behavioural therapy and graded exercise therapy in a recent trial, but
      are likely to experience less improvement in physical function. Outcomes were
      predicted by fatigue, disability and pain at assessment.

PMID- 23538644
TI  - Refeeding syndrome in very-low-birth-weight intrauterine growth-restricted
      neonates.
AB  - OBJECTIVE: Determine the incidence of refeeding syndrome, defined by the presence
      of hypophosphatemia in very-low-birth-weight (VLBW) infants with intrauterine
      growth restriction (IUGR) compared with those without IUGR. STUDY DESIGN: In this
      retrospective cohort study, VLBW infants admitted over a 10-year period (271 IUGR
      and 1982 non-IUGR) were evaluated for specific electrolyte abnormalities in the
      first postnatal week. RESULT: IUGR infants were significantly more likely to have
      hypophosphatemia (41% vs 8.9%, relative risk (95% confidence interval: 7.25
      (5.45, 9.65)) and severe hypophosphatemia (11.4% vs 1%, 12.06 (6.82, 21.33)) in
      the first postnatal week. The incidence of hypophosphatemia was significantly
      associated with the presence of maternal preeclampsia in all VLBW infants (odds
      ratio (OR): 2.58 (1.96, 3.40)) when controlling for birth weight and gestational
      age. CONCLUSION: Refeeding syndrome occurs in VLBW infants with IUGR and born to
      mothers with preeclampsia. Close monitoring of electrolytes, especially
      phosphorus, is warranted in this population.

PMID- 23538645
TI  - Cronobacter: an emerging opportunistic pathogen associated with neonatal
      meningitis, sepsis and necrotizing enterocolitis.
AB  - Members of the genus Cronobacter are an emerging group of opportunist Gram
      negative pathogens. This genus was previously thought to be a single species,
      called Enterobacter sakazakii. Cronobacter spp. typically affect low-birth-weight
      neonates, causing life-threatening meningitis, sepsis and necrotizing
      enterocolitis. Outbreaks of disease have been associated with contaminated infant
      formula, although the primary environmental source remains elusive. Advanced
      understanding of these bacteria and better classification has been obtained by
      improved detection techniques and genomic analysis. Research has begun to
      characterize the virulence factors and pathogenic potential of Cronobacter.
      Investigations into sterilization techniques and protocols for minimizing the
      risk of contamination have been reviewed at national and international forums. In
      this review, we explore the clinical impact of Cronobacter neonatal and pediatric
      infections, discuss virulence and pathogenesis, and review prevention and
      treatment strategies. 

PMID- 23538646
TI  - The MNA in 2013 - still going stronger after almost twenty years.

PMID- 23538647
TI  - Malnutrition: a highly predictive risk factor of short-term mortality in elderly
      presenting to the emergency department.
AB  - OBJECTIVES: To identify independent risk factors of mortality among elderly
      patients in the 3 months after their visit (T3) to an emergency department (ED).
      DESIGN: Prospective cohort study. SETTING: University hospital ED in an urban
      setting in France. PARTICIPANTS: One hundred seventy-three patients aged 75 and
      older were admitted to the ED over two weeks (18.7% of the 924 ED visits). Of
      these, 164 patients (94.8%) were included in our study, and 157 (95.7%) of them
      were followed three months after their ED visit. MEASUREMENTS: During the
      inclusion period (T0), a standardized questionnaire was used to collect data on
      socio-demographic and environmental characteristics, ED visit circumstances,
      medical conditions and geriatric assessment including functional and nutritional
      status. Three months after the ED visits (T3), patients or their caregivers were
      interviewed to collect data on vital status, and ED return or hospitalization.
      RESULTS: Among the 157 patients followed at T3, 14.6% had died, 19.9% had
      repeated ED visits, and 63.1% had been hospitalized. The two independent
      predictive factors for mortality within the 3 months after ED visit were:
      malnutrition screened by the Mini Nutritional Assessment short-form (MNA-SF)
      (OR=20.2; 95% CI: 5.74-71.35; p<.001) and the Cumulative Illness Rating Scale for
      Geriatrics (CIRS-G) score (OR=1.1; 95% CI: 1.01-1.22; p=.024). CONCLUSION:
      Malnutrition is the strongest independent risk factor predicting short-term
      mortality in elderly patients visiting the ED, and it was easily detected by MNA
      SF and supported from the ED visit.

PMID- 23538648
TI  - Malnutrition in community-dwelling adults with dementia (NutriAlz Trial).
AB  - OBJECTIVES: The objective of this study is to assess the nutritional status,
      measured by the MNA, in community-dwelling elderly individuals with dementia and
      to identify clinical risk factors for nutritional risk or malnutrition. DESIGN:
      Cross-sectional analysis of a cluster randomized clinical trial (Nutrialz).
      SETTING: Community-dwelling individuals attending dementia clinics. PARTICIPANTS:
      940 individuals. MEASUREMENTS: The clinical scales assessed were Mini Nutritional
      Assessment (MNA), Eating Behaviour Scale (EBS), Charlson comorbidity index,
      Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Basic
      Activities of Daily Living (BADL) score, Instrumental Activities of Daily Living
      (IADL) score, Neuropsychiatric Inventory Questionnaire (NPI-Q), Cornell
      depression scale and Zarit Caregiver Burden Interview. RESULTS: 5.2% of
      participants were classified as being malnourished, 42.6% as being at risk of
      malnutrition and 52.2% as well nourished. Malnutrition by type of dementia was
      more frequent in Lewy bodies dementia (18.2%) than in the other types. Worse
      nutritional status is significantly related to more advanced age and worse
      cognitive, functional and behavioural profile, as well as increased burden for
      caregivers. Presence of behavioural symptoms is significantly related to worse
      nutritional level for all NPI-Q symptoms but depression, exaltation, lack of
      inhibition and irritability. The items more strongly related to malnutrition are
      appetite/feeding and hallucinations. Dependence in any basic or instrumental ADL
      is significantly related to higher risk of malnutrition. Dependence on feeding is
      a strongly related risk factor, while food preparation is only a moderate one. A
      logistic regression model to predict at risk/malnutrition kept as significant
      risk factors EBS (Odds Ratio (OR) 0.84, 95%CI 0.78 to 0.91), Cornell (OR 1.12,
      95%CI 1.09 to 1.16), the number of dependent BADL (OR 1.29, 95%CI 1.17 to 1.42),
      age (OR 1.04, 95%CI 1.02-1.06), MMSE (OR 0.95, 95%CI 0.92 to 0.98) and Charlson
      (OR 1.18, 95%CI 1.05 to 1.34). A similar model built for prediction of
      malnutrition retained as significant covariables only EBS, Cornell and the number
      of dependent BADL. CONCLUSION: These results will allow a better understanding of
      the clinical stage previous to malnutrition. An adequate diagnosis and treatment
      of identified modifiable factors like functional impairment, eating behaviours
      and depression could delay or avoid malnutrition.

PMID- 23538649
TI  - Nutritional status of geriatric outpatients with systolic heart failure and its
      prognostic value regarding death or hospitalization, biomarkers and quality of
      life.
AB  - INTRODUCTION: The prevalence of malnutrition in ambulatory patients with heart
      failure is difficult to determine, depending on the timing and methodology.
      OBJECTIVE: To determine the nutritional status of outpatients with systolic heart
      failure with the Mini Nutritional Assessment (MNA) full and short-form versions,
      and evaluate its relationship with the short-term prognosis, biomarkers and
      quality of life. METHODS: Fifty consecutive (70% male), geriatric (74.3+ 6.2years
      old) stable outpatient with heart failure (NYHA class II 68%, III 32%) and left
      ventricular ejection fraction of 26.7 +11.5% were included and followed during 12
      months. At a routine visit to the heart failure clinic, the MNA, the Minnesota
      Living with Heart Failure questionnaire (MLHFQ) were applied. According to the
      MNA screening score the nutritional status was classified using the MNA full (MNA
      F) and the short-form (MNA-F) versions of the questionnaire. The recorded events
      were death and hospitalization. STATISTICS: The survival and hospitalizations
      curves were evaluated with the Log-Rank test and Cox Regression analysis. The
      association between parameters was analyzed with the Pearson and Spearmann
      correlation coefficient. RESULTS: (1) The mortality and hospitalization rates
      were 12% and 42%, respectively. (2) With the MNA-SF 7.6% of the patients had
      malnutrition and 20% were at risk of malnutrition. There was a good agreement
      (90%) between the MNA-SF and the MNA-F classifications. (3) There was a
      significant relationship between the MNA screening score and the MLHFQ (rs= 
      0.592 p<0.001), Nt-ProBNP (rs= -0.49 p<0.001) and total plasma protein (r= 0.672
      p=0.006); (3) The MNA-SF nutritional classification was associated with the 12
      months survival (Log-Rank p=0.044) and hospitalization (Log-Rank p=0.005) curves.
      (4) Those patients with malnutrition by the MNA-SF were at greater risk of death
      (HR= 8.0 p=0.059) and hospitalization (HR 8.1 p=0.008). CONCLUSION: The MNA is
      useful for the evaluation of the nutritional status of elderly outpatients with
      systolic heart failure. It is a good predictor of the short-term outcome and is
      also associated with the quality of life and Nt-ProBNP.

PMID- 23538650
TI  - Malnutrition in Turkish nursing homes: a correlate of short term mortality.
AB  - OBJECTIVE: Elderly nursing home residents are under high risk of malnutrition.
      Early interventions to prevent malnutrition may play a critical role in
      malnutrition-mortality correlation. This study aimed to obtain insight into the
      prevalence of malnutrition in nursing homes in the capital city of Turkey and the
      role of malnutrition in predicting the risk for short-term mortality. DESIGN:
      This study was conducted in seven different residential care facilities in
      Ankara. MEASUREMENTS: Nutritional status was evaluated by Mini Nutritional
      Assessment-Short Form. RESULTS: The mean age of the 534 participants was 79.46+/
      7.22 years. Nutritional assessment revealed that 15.9% of all older adults
      suffered from malnutrition and another 53.6% were at risk of malnutrition. The
      mortality rate for all subjects was 118 (22.1%) over 18 months, which was
      significantly higher in participants with malnutrition. CONCLUSIONS: We noted a
      high prevalence of malnutrition and a strong correlation of increased mortality
      with malnutrition in nursing home residents. Given the negative impact of
      malnutrition on mortality and morbidity, an emphasis should be placed on an
      effective nutritional policy in nursing homes.

PMID- 23538651
TI  - Nutritional screening strategy in nonagenarians: the value of the MNA-SF (mini
      nutritional assessment short form) in NutriAction.
AB  - OBJECTIVES: To identify older subjects at risk of malnutrition using the most
      appropriate tool available for the specific setting and to evaluate the Mini
      Nutritional Assessment short form (MNA-SF) in a sample of nonagenarians. DESIGN:
      Questionnaire based national screening week for the risk and prevalence of
      malnutrition in older people (NutriAction). SETTING: Older people in the
      community (CD) and in nursing homes (NH). PARTICIPANTS: General practices (n=70)
      and Nursing Homes (n=70). MEASUREMENTS: Questionnaire based on items from
      validated screening instruments: the MNA-SF, the Short Nutritional Assessment
      Questionnaire (SNAQ) and additional clinically relevant parameters (mobility,
      independence, social isolation and co-morbidities). RESULTS: In total 5,334
      people were screened of which 16% were aged over 90 years. In this age group, 66%
      of the screened individuals were at risk of malnutrition (MNA <= 11), and women
      were affected significantly more than men (p<0.001). Actual malnutrition was
      present in 22% (BMI <20), 20% (SNAQ) and 25% (clinical evaluation). The MNA
      appeared to be very sensitive but had a low specificity as well in the
      nonagenarians (98% and 44%) as in the younger old (97% and 52%). The SNAQ was not
      a sensitive tool for detecting malnutrition in this study population (25%).
      Although clinical impression had a low sensitivity (60-61%) it has a good
      specificity (86% in 90+ and 91% below 90yr). CONCLUSION: The overall risk of and
      the prevalence of malnutrition is common in older people. The prevalence is
      higher in women, in nursing homes and in older age groups. The MNA-SF followed by
      a clinical subjective evaluation seems to be the preferred strategy for detecting
      malnutrition in nonagenarians.

PMID- 23538652
TI  - The relationship between nutritional status, functional capacity, and health
      related quality of life in older adults with type 2 diabetes: a pilot explanatory
      study.
AB  - OBJECTIVE: To explore the relationship between nutritional status, functional
      capacity and health-related quality of life (HRQoL) in older adults with type 2
      diabetes (T2DM). DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Forty
      two non-insulin dependent older adults from a primary care center in Seville,
      Spain. MEASUREMENTS: Function was assessed with a battery of standardized
      physical fitness tests. Nutritional status was assessed using the Mini
      Nutritional Assessment (MNA) and the European Quality of Life Questionnaire (EQ
      5D-3L) was used to assess HRQoL. RESULTS: There was an association between MNA
      nutritional status and lower body strength as assessed by the chair sit-stand
      test (rho= .451; p= .037) and between MNA-nutritional status and EQ-5D-3L-HRQoL
      (EQ-5D-3Lutility, rho= .553; p<.001 and EQ-5D-3LVAS rho= .402; p<.001). An MNA
      item by item correlation analysis with HRQoL and lower limb strength demonstrated
      that HRQoL appears to be related to functional capacity (principally lower body
      strength, motor agility and cardiorespiratory fitness) among participants. These
      results were maintained when correlations were adjusted for co-morbidity.
      CONCLUSION: Our results demonstrated that nutritional status is moderately
      associated with HRQoL and lower limb strength in patients with T2DM. Our data
      suggest that more emphasis should be placed on interventions to encourage a
      correct diet and stress the needed to improve lower body strength to reinforce
      better mobility in T2DM population.

PMID- 23538653
TI  - Nutrition screening of older people in a community general practice, using the
      MNA-SF.
AB  - BACKGROUND:  OBJECTIVE: The study aimed to determine the prevalence of
      malnutrition risk in a population of older people (aged 75 years and over)
      attending a community general practice and identify characteristics of those
      classified as malnourished or at risk of malnutrition. DESIGN: Cross-sectional
      study of nutritional risk screen conducted over a six month period. PARTICIPANTS
      AND SETTING: Patients attending a general practice clinic in Victoria, Australia,
      who attended for the "75 plus" health assessment check. MEASUREMENTS: The Mini
      Nutritional Assessment Short Form (MNA(r)-SF) was included as part of the health
      assessment. Information was collected on living situation, co-morbidities,
      independence with meal preparation and eating, number of medications. Height and
      weight was measured and MNA(r)-SF score recorded. RESULTS: Two hundred and twenty
      five patients attending a general practice for a health assessment with a mean
      age of 81.3(4.3)(SD) years, 52% female and 34% living alone. Only one patient was
      categorised by the MNA(r)-SF as malnourished, with an additional 16% classified
      as at risk of malnutrition. The mean Body Mass Index (BMI) of the at-risk group
      was significantly lower than the well-nourished group (23.6 +/- 0.8 (SEM) vs 27.4
      +/- 0.3; p=0.0001). However, 34% of the at-risk group had a BMI of 25 or more
      with only 13% in the underweight category. CONCLUSION: In this population of
      older adults attending their general practitioner for an annual health
      assessment, one in six were identified as being at nutritional risk which is an
      additional risk factor for a severe health issue. Importantly, one third of the
      at-risk group had a BMI in the overweight or obese category, highlighting that
      older people can be at nutritional risk although they may be overweight or obese.

PMID- 23538654
TI  - Screening for malnutrition among nursing home residents - a comparative analysis
      of the mini nutritional assessment, the nutritional risk screening, and the
      malnutrition universal screening tool.
AB  - BACKGROUND: The European Society for Clinical Nutrition and Metabolism (ESPEN)
      has recommended the Mini Nutritional Assessment (MNA(r)), the Nutritional Risk
      Screening 2002 (NRS), and the Malnutrition Universal Screening Tool (MUST) for
      nutritional screening in various settings and age groups. While in recent years
      all three tools have been applied to nursing home residents, there is still no
      consensus on the most appropriate screening tool in this specific setting. AIM:
      The present study aims at comparing the MNA, the NRS, and the MUST with regard to
      applicability, categorization of nutritional status, and predictive value in the
      nursing home setting. METHOD: MNA, NRS, and MUST were performed on 200 residents
      from two municipal nursing homes in Nuremberg, Germany. Follow-up data on
      infection, hospitalization, and mortality were collected after six and again
      after twelve months. RESULTS: Among 200 residents (mean age 85.5 +/- 7.8 years)
      the MNA could be completed in 188 (94.0%) and the NRS and MUST in 198 (99.0%)
      residents. The prevalence of 'malnutrition' according to the MNA was 15.4%. The
      prevalence of 'risk of malnutrition' (NRS) and 'high risk of malnutrition'
      (MUST), respectively, was 8.6% for both tools. The individual categorization of
      nutritional status showed poor agreement between NRS and MUST on the one hand and
      MNA on the other. For all tools a significant association between nutritional
      status and mortality was demonstrated during follow-up as classification in
      'malnourished', respectively 'high risk of malnutrition' or 'nutritional risk',
      was significantly associated with increased hazard ratios. However, the MNA
      showed the best predictive value for survival among well-nourished residents.
      CONCLUSION: The evaluation of nutritional status in nursing home residents by
      MNA, NRS, and MUST shows significant differences. This observation may be of
      clinical relevance as nutritional intervention is usually based on screening
      results. As the items of the MNA reflect particularities of the nursing home
      population, this tool currently appears to be the most suitable one in this
      setting.

PMID- 23538655
TI  - Agreement between different versions of MNA.
AB  - Malnutrition occurs frequently in the elderly with important clinical and
      functional consequences. Moreover, the treatment of malnutrition in the elderly
      may be effective if clinical and nutritional interventions are performed in the
      early stages. Therefore the early identification of the risk of malnutrition
      using validated and handy tools plays a pivotal role in terms of clinical
      outcome. Mini Nutritional Assessment (MNA) was validated for this purpose since
      many years but it is still ongoing the debate over whether the use of different
      items in certain clinical conditions can be effective without affecting the
      validity of the nutritional status evaluation. The aim of this study was to
      assess the agreement between different versions of MNA in the evaluation of
      nutritional risk in elderly subjects. METHODS: 522 subjects, 345 women and 177
      men, were recruited from nursing homes or were free living in three different
      regions in Italy. All subjects underwent a multidimensional geriatric evaluation,
      addressed especially to nutritional status. We compared three different versions
      of MNA: the "original" version; a "proportional" MNA (MNA- P) in which the total
      MNA score was replaced by the ratio between the maximum score that each subject
      could obtain without including the body mass index (BMI) and the total original
      MNA score; and a third version in which calf circumference (CC) and mid- upper
      arm circumference (MAC) were used instead of BMI. RESULTS: According to the
      original MNA, a high prevalence of malnutrition was found out in both genders
      (26% of women and 16.3% of men); both the versions of MNA, in which BMI was not
      considered, showed a good predictive value compared to original MNA. In
      particular, the MNA- P. showed an overall efficiency equal to 89,1% with
      specificity and positive predictive value respectively equal to 97.5% and 95.2%.
      MNA- CC- MAC showed even better results in terms of overall efficiency (91.4%),
      sensitivity (81.1%), specificity (97.1%), positive and negative predictive values
      (94.2% and 94.4%, respectively). CONCLUSION: The different versions of MNA gave
      similar results in the classifications of subjects and in comparison with
      nutritional and biochemical parameters. Moreover MNA versions that did not
      considered BMI seem to be more effective in singling out subjects with risk
      factors related to malnutrition (disability, reduced strength and calf
      circumference, anaemia).

PMID- 23538656
TI  - A self-completed nutrition screening tool for community-dwelling older adults
      with high reliability: a comparison study.
AB  - OBJECTIVES: Malnutrition is common in community-dwelling older adults and is
      associated with poor outcomes including hospitalization and mortality. Recently,
      a 6-question short form mini nutritional assessment (SF-MNA) was validated for
      rapid nutrition screening. Ideally, nutrition screening could be performed by
      individuals or their caregivers prior to or during an outpatient clinical visit,
      thus allowing for the ongoing monitoring of nutritional status among older
      adults. DESIGN: We compared the SF-MNA administered by a healthcare professional
      (HCP) to a 6-item self-administered screening tool (Self-MNA) in 463 community
      dwelling older adults who gave informed consent. The population was 60% women
      with a mean age of 76.8+/-6.8 years. The HCP was blinded to the results of the
      Self-MNA questionnaire. RESULTS: Using the SF-MNA, 27% of subjects were
      malnourished, 38% were at risk, and 35% had normal nutrition status. The
      agreement between the Self-MNA and the SF-MNA was 99% (Self-MNA sensitivity 99%,
      specificity 98%, false negative rate 1%, false positive rate 2%) for identifying
      Malnourished subjects and 83% (sensitivity 89%, specificity 77%, false negative
      rate 11%, false positive rate 23%) for identifying At Risk of Malnutrition
      compared to the MNA-SF administered by a HCP. CONCLUSION: We found that the Self
      MNA demonstrates sufficient inter-rater reliability for use in nutrition
      screening among community-dwelling older adults. Further validation studies and
      the possible impact of language translation should be pursued.

PMID- 23538657
TI  - Malnutrition is related to functional impairment in older adults receiving home
      care.
AB  - OBJECTIVES: The aims of this work were (a) to provide a detailed description of
      the association between nutritional (Mini Nutritional Assessment; MNA(r)) and
      functional status in a sample of older adults receiving home care, using both
      questionnaire- and performance-based functional methods, and (b) to investigate
      the impact of different MNA subscales on this association. DESIGN: Multi-centre,
      cross-sectional. SETTING: Home care. PARTICIPANTS: 296 persons >=65 years in need
      of care (80.7+/-7.7 y). MEASUREMENTS: Nutritional status was determined by the
      MNA and functional status by two questionnaires (Instrumental and Basic
      Activities of Daily Living; IADL, ADL) and three performance tests (handgrip
      strength, HGS; Short Physical Performance Battery, SPPB; Timed 'Up and Go' Test,
      TUG). A categorical and a covariance analytical approach were used to test for
      differences in functional status between MNA groups (well nourished, risk of
      malnutrition, malnourished). In addition, functional parameters were correlated
      with total MNA, a modified MNA version (modMNA), where functional items were
      excluded, and MNA subscales ('functionality', 'general assessment',
      'anthropometry', 'dietary assessment', and 'subjective assessment'). RESULTS: 57%
      of the participants were at risk of malnutrition and 12% malnourished. 35%
      reported severe limitations in IADL, 18% in ADL. 40%, 39% and 35% had severe
      limitations in HGS, SPPB and TUG; 9%, 28% and 34% were not able to perform the
      tests. Functional status deteriorated significantly from the well nourished to
      the malnourished group in all functional measures. The modMNA was weak but still
      significantly related to all functional parameters except TUG. The subscale
      'functionality' revealed strongest correlations with functional measures. All
      other MNA subscales showed only weak or no associations. CONCLUSION: More than
      one half of the seniors receiving home care were at nutritional risk and poor
      functional level, respectively. Malnutrition according to MNA was significantly
      associated to both questionnaire- and performance-based functional measures even
      after exclusion of functional MNA items.

PMID- 23538658
TI  - Nutritional status according to the mini nutritional assessment (MNA(r)) and
      frailty in community dwelling older persons: a close relationship.
AB  - OBJECTIVE: This study investigates the association between MNA results and
      frailty status in community-dwelling older adults. In addition the relevance of
      singular MNA items and subscores in this regard was tested. DESIGN: Cross
      sectional study. SETTING: Community-dwelling older adults were recruited in the
      region of Nurnberg, Germany. PARTICIPANTS: 206 volunteers aged 75 years or older
      without cognitive impairment (Mini Mental State Examination >24 points), 66.0%
      female. MEASUREMENTS: Frailty was defined according to Fried et al. as presence
      of three, pre-frailty as presence of one or two of the following criteria: weight
      loss, exhaustion, low physical activity, low handgrip strength and slow walking
      speed. Malnutrition (<17 points) and the risk of malnutrition (17-23.5 points)
      were determined by MNA(r). RESULTS: 15.1% of the participants were at risk of
      malnutrition, no participant was malnourished. 15.5 % were frail, 39.8% pre-frail
      and 44.7% non-frail. 46.9% of the frail, 12.2% of the pre-frail and 2.2% of the
      non-frail participants were at risk of malnutrition (p<0.001). Hence, 90% of
      those at risk of malnutrition were either pre-frail or frail. For the
      anthropometric, dietary, subjective and functional, but not for the general MNA
      subscore, frail participants scored significantly lower than pre-frail (p<0.01),
      and non-frail participants (p<0.01). Twelve of the 18 MNA items were also
      significantly associated with frailty (p<0.05). CONCLUSIONS: These results
      underline the close association between frailty syndrome and nutritional status
      in older persons. A profound understanding of the interdependency of these two
      geriatric concepts will represent the basis for successful treatment strategies.

PMID- 23538660
TI  - "It could probably help someone else but not me": a feasibility study of a snack
      programme offered to meals on wheels clients.
AB  - OBJECTIVES: Community-based services, such as Meals on Wheels (MOW), allow older
      adults to remain in their homes for as long as possible. Many MOW recipients
      experience decreased appetite that limits intake at mealtimes. This pilot study
      aimed to determine the feasibility of providing high protein high energy snacks
      to improve nutrient intakes of MOW clients in a regional centre of New South
      Wales, Australia. PARTICIPANTS: A convenience sample of 12 MOW clients.
      INTERVENTION: Participants received snacks five times a week, in addition to
      their usual MOW order, for four weeks. MEASUREMENTS: Nutritional status was
      assessed using the Mini Nutritional Assessment tool. Pre-post changes in dietary
      intake were assessed using a diet history and food frequency questionnaire.
      Qualitative interviews conducted in clients' homes were digitally recorded,
      transcribed verbatim, and themes identified. RESULTS: Post-intervention, there
      was a trend for an increased energy (mean = +415kJ (SD=1477) /day) and protein
      (+7.2 (+/-14.06) g/day) intake. MNA scores significantly increased (P= 0.036) and
      proportion of respondents categorised as 'malnourished' or 'at risk of
      malnutrition' decreased from 17% to 8%, and 67% to 25%, respectively (P <0.05).
      Mean body weight increased from 67.1 (+/-14.3) to 67.8 (+/-14.8) (P= 0.008),
      while Body Mass Index (BMI) increased by a mean of 0.78 (+/-1.16) kg/m2 (P =
      0.039). Only half of participants indicated interest in continuing with the
      program. Reasons included the role of snacks serving as a reminder to eat, as
      well as their perceived nutritional value. Identified barriers included perceived
      lack of need for additional food, ability to self-provide such items, and a
      perceived adequate health status. CONCLUSION: Provision of an additional daily
      mid-meal snack may be a useful addition to existing MOW services, for improved
      energy and protein intakes. However, not all MOW clients at risk of malnutrition
      perceived the snacks to be beneficial to them.

PMID- 23538659
TI  - Screening for malnutrition in nursing home residents: comparison of different
      risk markers and their association to functional impairment.
AB  - OBJECTIVES: To identify nursing home residents with malnutrition or at risk of
      malnutrition by using different markers, determine if the Mini Nutritional
      Assessment (MNA(r)) is able to identify all residents at risk according to single
      risk markers and explore the relation between risk markers and functional
      impairment. DESIGN: Cross-sectional study. SETTING: Six German nursing homes.
      PARTICIPANTS: 286 residents (86+/-7y, 89% female). MEASUREMENTS: Screening for
      malnutrition or its risk included low BMI (<=22 kg/m2), recent weight loss (WL),
      low food intake (LI) as single risk markers and MNA (<24 points, p.) as composite
      marker. Prevalence of single nutritional risk markers in different MNA categories
      was compared by cross-tables. Mental (cognition, mood) and physical function
      (mobility) were assessed by interviewing nursing staff and association of
      impaired status to nutritional risk markers determined by Chi2 test. RESULTS:
      32.9% of residents had a low BMI, 11.9% WL and 21.3% LI. 60.2% were categorized
      malnourished (18.2%) or at risk of malnutrition (42.0%) by MNA. 64% presented at
      least one of these nutritional risk markers. Of those classified malnourished by
      MNA, 96.2% also showed low BMI, WL or LI. In contrast, eleven residents (9.6%)
      considered well-nourished by MNA presented single risk markers (9 low BMI, 2 WL).
      Cognitive impairment, depressive symptoms and immobility was present in 59.0%,
      20.8% and 25.5%, respectively. Functional impairment, and in particular severe
      impairment, was to a higher proportion present in residents at nutritional risk
      independent of the chosen marker (MNA<24 p., low BMI, WL, LI). CONCLUSION: The
      high prevalence of nutritional risk highlights the importance of regular
      screening of nursing home residents. The MNA identified nearly all residents with
      low BMI, WL and LI. The close association between nutritional risk and functional
      impairment requires increased awareness for nutritional problems especially in
      functionally impaired residents, to early initiate nutritional measures and thus,
      prevent further nutritional and functional deterioration.

PMID- 23538661
TI  - Ankle-brachial pressure index and mini nutritional assessment in community
      dwelling elderly people.
AB  - BACKGROUND: A low ankle-brachial pressure index (an ABPI value <0.90) is
      considered predictive of cardiovascular disease, and is widely thought to
      increase morbidity and mortality in the elderly. However, good nutrition is
      beneficial both for the health and the ability to resist and recover from the
      disease. OBJECTIVE: The aim of the present study was to evaluate the relationship
      between the ankle-brachial pressure index and the nutritional status of the
      elderly in a city of Kochi prefecture, Japan. METHODS: This was a cross-sectional
      study in which a total of 100 elderly people, both males and females, were
      screened for ankle-brachial pressure index (ABPI), nutritional status (through
      the use of the short form of the mini nutritional assessment), activities of
      daily living, lifestyle, gait speed (10MWT), postural stability (OLST), and
      functional mobility (TUG). RESULTS: About 67% of the participants were found to
      have a normal nutritional status, 27% were at risk of malnutrition, and six
      percent were classified as malnourished. The mean ABPI of the participants was
      1.08+/-0.10, and three participants had an ABPI lower than 0.90. The ABPI was
      statistically higher in well nourished participants compared with those at risk
      of malnutrition or the malnourished. The mean ABPI was significantly higher in
      non-smokers compared with former smokers. The ABPI was found to correlate
      negatively with gait speed and with TUG score. CONCLUSION: Well-nourished elderly
      had a higher normal ankle-brachial pressure index as compared with the
      malnourished elderly. This study provides supportive evidence for the necessity
      of adequate nutrition for elderly people.

PMID- 23538663
TI  - Capacity to consent to biomedical research's evaluation among older cognitively
      impaired patients. A study to validate the University of California Brief
      Assessment of Capacity to Consent questionnaire in French among older cognitively
      impaired patients.
AB  - CONTEXT: Some studies have highlighted the difficulty for physicians to evaluate
      patient's ability to consent to bio-medical research in the elderly population.
      The University of California Brief Assessment of Capacity to Consent (UBACC) is a
      rapid questionnaire to assess the ability to consent, previously validated among
      schizophrenic patients. OBJECTIVE: To evaluate the accuracy of the UBACC scale,
      French version, to determine the capacity to consent to biomedical studies of
      older people with normal cognition, mild cognitive impairment (MCI) or Alzheimer
      Disease (AD). DESIGN: A prospective validation study between September 2008 to
      November 2011. SETTING: A Memory clinic. PATIENTS: We included 61 subjects in a
      memory clinic who had already consented to participate to a biomedical research
      and had signed a consent form. Those subjects, who had memory impairment, had a
      comprehensive neuro-psychological (including Mini Mental State Examination
      (MMSE)/30), clinical, biological assessment and brain imagery during day-care
      hospital. They were classified as MCI or AD patients. Control group included
      patients' caregivers without memory complaints and a normal comprehensive neuro
      psychological assessment. INTERVENTION AND MEASUREMENTS: The consent form was
      once again explained to the subjects by a physician who subjectively evaluated if
      subjects had understood the study. Then, the 10 questions of the French version
      of the UBACC scale (max score 20) were asked to the participants. This scale
      evaluates the understanding of the study's aim, risks and benefits. A comparison
      was made between subjective assessment and the UBACC score. RESULTS: The
      physician considered that 18/61 patients (2 MCI and 16 AD) had not understood.
      These ones had a lower UBACC score (Score/20 (SD) [range]: 7.56 (3.03) [0-12]
      versus 17.72 (2.68) [13-28], p<0.001), a lower MMSE (Score/ 30 (SD): 21.1 (5.9)
      versus 27.3 (2.9); p<0.001) and were older (age (years old) 80.8 versus 76.6.
      p<0.0001) compared to those who had understood. Moreover, all the patients who
      had not understood had an UBACC score <= 12. The administration time was accurate
      in this population (<10 minutes). CONCLUSION: The UBACC scale, in its French
      version, was accurate to assess capacity to consent in an older, cognitively
      impaired population.

PMID- 23538662
TI  - Body mass index, lifestyles, physical performance and cognitive decline: the
      "Treviso Longeva (TRELONG)" study.
AB  - OBJECTIVES: The relative contributions of risk factors, as body mass index (BMI),
      depression, chronic diseases, smoking, and lifestyles (as physical and
      performance activity, social contacts and reading habit) to cognitive decline in
      the elderly are unclear. We explored these variables in relation to 7-year
      cognitive decline in long-lived Italian elderly. DESIGN: Secondary data analysis
      of a longitudinal study of a representative, age-stratified, population sample.
      SETTING: The TREVISO LONGEVA (TRELONG) Study, in Treviso, Italy. PARTICIPANTS:
      120 men and 189 women, age 77 years and older (mean age 80.2 +/- 6.9 years)
      survivors after seven years of follow up. MEASUREMENTS: Cognitive decline
      measured as difference between Mini-Mental State Examination (MMSE) score in 2003
      and in 2010; Body mass index (BMI), handgrip, Short Physical Performance Battery
      (SPPB) score, social contacts, reading habit, sight, hearing, schooling,
      mediterranean diet and multiple clinical and survey data recorded at baseline in
      2003. RESULTS: In separate univariate analyses, age, SPPB score < 5, depressive
      symptoms (GDS) and more comorbidities (CCI) were associated with greater
      cognitive decline. Otherwise higher BMI, higher handgrip, reading habit, non
      deteriorated sight and hearing, and schooling were protective. In a final
      multivariate model, age and higher BMI were associated with greater cognitive
      decline while reading habits was protective. SPPB score < 5 tends, though weakly,
      to be associated with greater cognitive decline. These associations remained with
      multivariate adjustment for gender, schooling, Charlson co-morbidity index (CCI)
      and baseline MMSE. CONCLUSION: Age and higher baseline BMI, independent of
      gender, and other confounding factors, are risk factors for cognitive decline.
      Reading habit plays a protective role seven years later among northern Italian
      adults aged 70 years or older. Low physical performance tends, though weakly, to
      be associated with greater cognitive decline.

PMID- 23538664
TI  - Effect of flavor enhancers on the nutritional status of older persons.
AB  - OBJECTIVES: This study on flavor enhancers aims to: 1) compare food intake of
      older persons, 2) determine changes in body weight, blood pressure and serum
      sodium and 3) determine tolerance/intolerance to the flavor enhancers. DESIGN:
      The project is a cross-over, double blind study design. SETTING: A nursing home
      for the aged, Golden Acres Institution located in Quezon City, Philippines.
      PARTICIPANTS: Sixty eligible subjects (31 males and 29 females), aged 60 years
      and over. INTERVENTION: Subjects were initially given: pouch A (0.5gram
      monosodium glutamate) or pouch B (0.5gram iodized salt) for lunch and supper for
      2 months. The intervention was switched after one week wash period. MEASUREMENTS:
      Before the start and during intervention, 24 hour food intake of subjects was
      recorded and anthropometric and clinical data were measured.
      Tolerance/intolerance to the flavor enhancer and data on the quality of life were
      evaluated using a pre-tested structured questionnaire. Paired t-test was used to
      determine significant changes among each period of dietary intervention between
      different groups. RESULTS: Energy intake and almost all nutrients increased for
      males and females for both interventions. Body weight and body mass index
      increased significantly for both gender with MSG usage but not with iodized salt.
      The diastolic blood pressure of all subjects was normal while the systolic blood
      pressure remained at pre-hypertension level before and after both interventions.
      The sodium serum was within normal levels for both groups for both interventions.
      It was also observed that systolic blood pressure increased in both groups while
      sodium levels did not. It was further observed that both MSG and iodized salt
      interventions were well tolerated by majority of the participants. CONCLUSION:
      The use of flavor enhancers have increased food intake and were well- tolerated
      among older persons. No difference in blood pressure and sodium serum was noted
      in both MSG and iodized salt intake. RECOMMENDATION: People with less appetite,
      especially among older persons can use flavor enhancers to improve their food
      intake and body weight. Sodium containing flavor enhancers can be part of a
      healthy diet for older persons when used in moderation.

PMID- 23538665
TI  - Snacking may improve physical function among older Americans.
AB  - BACKGROUND/OBJECTIVES: Snacking was reported to provide nutritional benefits
      among older adults, but the association between such dietary behavior and health
      outcomes has not been clearly established. The purpose of this study is to
      examine the associations between snacking and gait speed, a performance-based
      measure of physical function. DESIGN: Cross-sectional population-based survey.
      SETTING: The 1999-2002 National Health and Nutrition Examination Survey (NHANES).
      PARTICIPANTS: A nationally representative sample of Americans aged 60 and older(n
      = 2,333). MEASUREMENTS: Participants were classified by snacking frequency (0, 1,
      2, 3, >=4 snacks/d) and by the contribution of snacking to their daily energy
      intake (0 to <10%, 10% to <20%, 20% to <30%, >=30%). Physical function was
      assessed by measurement of gait speed over 20 feet. RESULTS: After adjusting for
      age, gender, education, race/ethnicity, smoking status, and marital status, older
      adults who snacked four times or more daily had a faster gait speed (P = 0.033)
      than non-snackers. Snacking that contributed 20% to <30% (P = 0.017) of energy
      was associated with a faster gait speed than snacking that contributed 0 to <10%
      of energy. Similar associations were observed after further adjustment for
      potential confounders. CONCLUSION: Both snacking frequency and percentage of
      energy from snacking are positively associated with gait speed among older
      adults. The benefits of snacking on older adults' physical function may warrant
      their inclusion in this population's diet.

PMID- 23538666
TI  - The nursing home population: an opportunity to make advances on research on
      multimorbidity and polypharmacy.

PMID- 23538667
TI  - Vitamin D supplementation in older adults: searching for specific guidelines in
      nursing homes.
AB  - BACKGROUND: The prevalence of vitamin D insufficiency is very high in the nursing
      home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated
      despite of strong clinical evidence and recommendations for supplementation. This
      review aims at reporting the current knowledge of vitamin D supplementation in NH
      and proposing recommendations adapted to the specificities of this institutional
      setting. DESIGN: Current literature on vitamin D supplementation for NH residents
      was narratively presented and discussed by the French Group of Geriatrics and
      Nutrition. RESULT: Vitamin D supplementation is a safe and well-tolerated
      treatment. Most residents in NH have vitamin D insufficiency, and would benefit
      from vitamin D supplement. However, only few residents are actually treated.
      Current specific and personalized protocols for vitamin D supplementation may not
      be practical for use in NH settings (e.g., assessment of serum vitamin D
      concentrations before and after supplementation). Therefore, our group proposes a
      model of intervention based on the systematic supplementation of vitamin D (1,000
      IU/day) since the patient's admission to the NH and throughout his/her stay
      without the need of a preliminary evaluation of the baseline levels. Calcium
      should be prescribed only in case of poor dietary calcium intake. CONCLUSION: A
      population-based rather than individual-based approach may probably improve the
      management of vitamin D insufficiency in the older population living in NH,
      without increasing the risks of adverse health problems. The clinical relevance
      and cost effectiveness of this proposal should be assessed under NH real-world
      conditions to establish its feasibility.

PMID- 23538668
TI  - The effectiveness of IDF and ATP-III in identifying metabolic syndrome and the
      usefulness of these tools for health-promotion in older Taiwanese.
AB  - OBJECTIVES: The aim of this study was to compare the effectiveness of IDF
      (International Diabetes Federation) and ATP-III (National Cholesterol Education
      Program-Adult Treatment Panel III) for predicting metabolic syndrome, and to
      evaluate the usefulness of these definitions for health promotion. DESIGN: A
      cross-sectional study. SETTING: A national random sample. PARTICIPANTS: A
      population representative sample of 1021 54-91 year-old Taiwanese. MEASUREMENTS:
      Subjects were measured for anthropometric and biochemical indicators and rated
      for the presence of metabolic syndrome using the two definitions. We evaluated
      the effectiveness of the two definitions in predicting MetS among those who had
      specific metabolic disorders. Results were analyzed with Student t-test and
      McNemar's test. RESULTS: Among the 918 subjects who had one or more MetS-item
      disorders, ATP-III rated greater proportions of subjects as having MetS than IDF,
      but both definitions predicted less than 50% (37.7% and 45.4%, respectively) as
      having MetS. CONCLUSION: Compared to IDF, ATP-III rated a greater proportion of
      subjects as having MetS, but both definitions missed more than 50% of subjects
      who had metabolic disorder(s). Since those who are missed have as much need for
      lifestyle intervention, the definitions appear not appropriate for health
      promotion.

PMID- 23538669
TI  - Two pairs of 1 : 2 nickel(II) and copper(II) metal-complex dyes showing the same
      trans configuration and azo-hydrazone transformation but different thermal
      properties.
AB  - Two pairs of 1: 2 neutral trans mononuclear transition-metal (M = Ni(II) and
      Cu(II)) complexes of pyridine-2,4-dione and quinoline-2,4-dione based
      heterocyclic dyes have been structurally and spectrally characterized and
      compared herein. X-ray single-crystal diffraction analyses of four complexes,
      namely trans-[Ni(La)2(DMF)2] (1), trans-[Cu(La)2(DMF)2] (2), trans
      [Ni(Lb)2(DMF)2] (3) and trans-[Cu(Lb)2(DMF)2] (4), reveal that they have the same
      trans configuration between the bidentate chelating dianionic ligands and two
      axially coordinated DMF molecules. Furthermore, a transformation from the
      hydrazone to azo configuration has been observed for both bidentate chelating
      ligands La(-) and Lb(-) after metal-ion complexation. More importantly, the
      simultaneous DSC/TG-MS-FTIR method has been used to explore the thermal stability
      of four neutral metal-complex dyes 1-4, where the two axially coordinated DMF
      molecules in Ni(II) and Cu(II) complexes exhibit distinguishable decomposition
      behavior because of their different M-O bond lengths originating from the Jahn
      Teller distortions.

PMID- 23538670
TI  - Cirrhosis is less cirrhosis without virus C.

PMID- 23538671
TI  - Building a super elongation complex for HIV.
AB  - A better understanding of the host cell protein complex that helps HIV replicate
      inside cells offers the possibility of new therapeutic targets.

PMID- 23538672
TI  - Highly stereoselective directed reactions and an efficient synthesis of
      azafuranoses from a chiral aziridine.
AB  - Polyhydroxylated pyrrolidines, such as biologically important azafuranoses
      represented by the natural product (+)-2,5-imino-2,5,6-trideoxy-gulo-heptitol and
      its C(3)-epimer, were elaborated from a commercially available enantiomerically
      pure (2R)-hydroxymethylaziridine by highly stereoselective directed reactions in
      more than 61% overall yield. At first, the nucleophile 2-trimethylsilyloxyfuran
      was directed to (2R)-aziridine-2-carboxaldehyde by ZnBr2 to yield the unusual
      anti-addition product as a single isomer via the chelation-controlled transition.
      The ring opening of aziridine was followed by conjugate addition to give a cis
      fused bicycle, which was converted to the target molecule after the required
      reductive operations.

PMID- 23538673
TI  - Prescribing in palliative care: a quest for appropriateness.

PMID- 23538674
TI  - Sequential observation of implanted endometriosis by laparoscopy in rats:
      correlation between the prevalence rate and the estrous cycle.
AB  - This study aimed to clarify the correlation between the estrous cycle and
      prevalence rate of endometriosis by sequential laparoscopy in Wistar-Imamichi
      female rats. The peritoneal implantation of endometrial tissue was performed in
      four estrous cycle rats (proestrus, estrus, metestrus, and diestrus). One week
      after implantation, the volume of the ectopic endometriosis was measured, and
      sequential laparoscopy was performed for 4 weeks to observe the prevalence rate.
      Five weeks after implantation, the volume of the ectopic endometriosis was
      measured again after laparoscopy. One week after implantation, the volume of
      endometriosis was significantly larger in proestrus and estrus rats than
      metestrus and diestrus rats. Prevalence rate was decreased with time. Five weeks
      after implantation, the prevalence rate and volume were higher and larger in the
      metestrus, diestrus, and estrus rats than in the proestrus rats. These results
      show that the estrous cycle affects the change of ectopic endometriosis. The
      decrease of prevalence rate was slow in metestrus, diestrus, and estrus rats as
      compared to that in proestrus rats. The volume of ectopic endometriosis showed
      little decrease with time when the endometrial tissue was implanted during the
      metestrus and diestrus portion of the cycle. Moreover, sequential laparoscopy
      made it possible to observe the prevalence rate of endometriosis.

PMID- 23538675
TI  - Prostaglandin D2 inhibits collagen secretion from lung fibroblasts by activating
      the DP receptor.
AB  - Lung fibroblasts are responsible for collagen secretion during normal tissue
      repair and the development of fibrosis. Many other prostaglandins have been
      reported to regulate collagen synthesis in lung fibroblasts, but the role of
      prostaglandin D2 (PGD2) is unknown. In this study, we investigated the effect of
      PGD2 on type I collagen secretion in human lung fibroblasts. Pretreatment with
      PGD2 (0.1 - 10 MUM, 1 h) significantly attenuated type I collagen secretion to
      the cell supernatant induced by transforming growth factor-beta (TGF-beta).
      Although an agonist on chemoattractant receptorhomologous molecule expressed on
      Th2 cells (CRTH2) did not have any effect, the prostanoid DP-receptor agonist
      BW245C (0.01 - 1 MUM) suppressed TGF-beta-induced collagen secretion. PGD2 and
      BW245C significantly increased intracellular cAMP level. One-hour pretreatment
      with forskolin (0.1 - 10 MUM), dibutyryl-cAMP (0.01 - 1 mM), and the protein
      kinase A (PKA)-activator N(6)-phenyl-cyclic AMP (100 MUM) significantly reduced
      TGF-beta-induced collagen secretion, while exchange protein activated by cAMP
      (Epac) activator 8-bromo-2'-O-methyladenosine-3',5'-cyclic AMP (10 MUM) did not
      affect collagen deposition. These results suggest that PGD2 inhibits TGF-beta
      induced collagen secretion via intracellular cAMP accumulation through activating
      DP receptor.

PMID- 23538676
TI  - Effect of overexpression of the brain-specific Na(+)/Ca(2+) exchanger splice
      variant NCX1.5 on NO cytotoxicity in HEK293 cells.
AB  - Nitric oxide (NO) induces cytotoxicity in neuronal and glial cells via activation
      of the Na(+)/Ca(2+) exchanger (NCX). This study examined the role of the
      predominant brain-specific NCX splice variant NCX1.5 in NO-induced cytotoxicity
      in the HEK293 cell expression system. Cells were transfected with the plasmid
      construct pcDNA3.1/V5-His containing full-length rat NCX1.5 cDNA. There was no
      difference in the cytotoxic effects of the NO donors sodium nitroprusside and S
      nitroso-N-acetylpenicillamine between control and transfected cells. These
      results suggest that NO cytotoxicity is not dependent on NCX1.5.

PMID- 23538677
TI  - Fisetin inhibits osteoclastogenesis through prevention of RANKL-induced ROS
      production by Nrf2-mediated up-regulation of phase II antioxidant enzymes.
AB  - Osteoclasts (OCLs) are multinucleated bone-resorbing cells that are
      differentiated by stimulation with receptor activator of nuclear factor kappa-B
      ligand (RANKL) and macrophage colony-stimulating factor. We recently demonstrated
      that regulation of heme-oxygenase 1 (HO-1), a stress-induced cytoprotective
      enzyme, also functions in OCL differentiation. In this study, we investigated
      effects of fisetin, a natural bioactive flavonoid that has been reported to
      induce HO-1 expression, on the differentiation of macrophages into OCLs. Fisetin
      inhibited the formation of OCLs in a dose-dependent manner and suppressed the
      bone-resorbing activity of OCLs. Moreover, fisetin-treated OCLs showed markedly
      decreased phosphorylation of extracellular signal-regulated kinase, Akt, and Jun
      N-terminal kinase, but fisetin did not inhibit p38 phosphorylation. Fisetin up
      regulated mRNA expression of phase II antioxidant enzymes including HO-1 and
      interfered with RANKL-mediated reactive oxygen species (ROS) production. Studies
      with RNA interference showed that suppression of NF-E2-related factor 2 (Nrf2), a
      key transcription factor for phase II antioxidant enzymes, rescued fisetin
      mediated inhibition of OCL differentiation. Furthermore, fisetin significantly
      decreased RANKL-induced nuclear translocation of cFos and nuclear factor of
      activated T cells cytoplasmic-1 (NFATc1), which is a transcription factor
      critical for osteoclastogenic gene regulation. Therefore, fisetin inhibits OCL
      differentiation through blocking RANKL-mediated ROS production by Nrf2-mediated
      up-regulation of phase II antioxidant enzymes.

PMID- 23538678
TI  - Pacemaker implantation in a patient with brugada and sick sinus syndrome.
AB  - Brugada syndrome (BrS) is a rare and inherited primary arrhythmic syndrome
      characterized by ST-segment elevations in the right precordial leads (V1-V3) with
      an increased risk of sudden cardiac death (SCD). Arrhythmias in BrS are often
      nocturne, and brady-arrhythmias are often seen in patients with loss-of-function
      mutations in SCN5A. In this case-report we present a 75-year old woman referred
      to our outpatient clinic for inherited cardiac diseases for a familial clinical
      work-up. Since childhood she had suffered from dizziness, absence seizures, and
      countless Syncope's. In 2004 sick sinus syndrome was suspected and she was
      treated with implantation of a pacemaker (PM) at another institution. An
      inherited cardiac disease was one day suddenly suspected, as the patient had a 61
      year old brother who was diagnosed with symptomatic BrS, and treated with an
      implantable cardioverter defibrillator (ICD) after aborted SCD. A mutation
      screening revealed a SCN5A [S231CfsX251 (c.692-693delCA)] loss-of-function
      mutation not previously reported, and as a part of the cascade screening in
      relatives she was therefore referred to our clinic. In the 7 year period after PM
      implantation she had experienced no cardiac symptoms, although her
      electrocardiogram changes now were consistent with a BrS type 1 pattern. A
      genetic test confirmed that she had the same mutation in SCN5A as her brother. In
      this case-report we present a loss-of function mutation in SCN5A not previously
      associated with BrS nor presented in healthy controls. Sinus node dysfunction has
      previously been documented in patients with symptomatic BrS, which suggests it is
      not a rare concomitant. The only accepted treatment of BrS is today implantation
      of an ICD. In the future studies should evaluate if PM in some cases of
      symptomatic BrS can be used instead of ICDs in patients with a loss-of-function
      SCN5A mutations.

PMID- 23538679
TI  - Diffuse hemolymphangioma of the rectum: a report of a rare case.
AB  - Intestinal hemolymphangioma is a rare vascular and lymphatic malformation and is
      manifested as anaemia and recurrent alimentary tract hemorrhage. Few cases of
      hemolymphangioma occurring in small intestine, spleen, esophagus and other organs
      have been reported. We herein report a case of a 37-year-old man with severe
      rectal bleeding. Digital examination revealed nodular mucosa. No rectal mass was
      palpated, but bleeding in the ampulla was detected. Colonoscopy revealed an
      extensive hypervascular submucosal lesion arising from the rectosigmoid junction
      colon to the distal edge of the anus. Endoscopic ultrasonography demonstrated an
      extensive anechoic mass with clear edge. Magnetic resonance imaging (MRI) showed
      a significant thickness of the rectal wall, extending to the distal edge of the
      anus, with a narrowing lumen. A sphincter-saving rectal surgery was performed.
      Due to a lack of knowledge of the clinical, endoscopic and radiological features,
      preoperative recognition of hemolymphangioma is not easy. Computed tomography and
      MRI are helpful in confirming the diagnosis, and defining the extent and invasion
      of the lesion. For the low malignant potential tumors, a sphincter-saving rectal
      surgery is recommended after a full evaluation of the tumor.

PMID- 23538680
TI  - Vaccines and recommendations for their use in inflammatory bowel disease.
AB  - The patient with inflammatory bowel disease will be predisposed to numerous
      infections due their immune status. It is therefore important to understand the
      immune and serologic status at diagnosis and to put the patient into an adapted
      vaccination program. This program would be applied differently according to two
      patient groups: the immunocompromised and the non-immunocompromised. In general,
      the first group would avoid the use of live-virus vaccines, and in all cases,
      inflammatory bowel disease treatment would take precedence over vaccine risk. It
      is important to individualize vaccination schedules according to the type of
      patient, the treatment used and the disease pattern.In addition, patient with
      inflammatory bowel disease should be considered for the following vaccines:
      varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide
      vaccine and hepatitis B vaccine.

PMID- 23538681
TI  - DNMT gene expression and methylome in Marek's disease resistant and susceptible
      chickens prior to and following infection by MDV.
AB  - Marek's disease (MD) is characterized as a T cell lymphoma induced by a cell
      associated alpha-herpesvirus, Marek's disease virus type 1 (MDV1). As with many
      viral infectious diseases, DNA methylation variations were observed in the
      progression of MD; these variations are thought to play an important role in host
      virus interactions. We observed that DNA methyltransferase 3a (DNMT3a) and 3b
      (DNMT3b) were differentially expressed in chicken MD-resistant line 6 3 and MD
      susceptible line 7 2 at 21 d after MDV infection. To better understand the role
      of methylation variation induced by MDV infection in both chicken lines, we
      mapped the genome-wide DNA methylation profiles in each line using Methyl-MAPS
      (methylation mapping analysis by paired-end sequencing). Collectively, the data
      sets collected in this study provide a more comprehensive picture of the chicken
      methylome. Overall, methylation levels were reduced in chickens from the
      resistant line 6 3 after MDV infection. We identified 11,512 infection-induced
      differential methylation regions (iDMRs). The number of iDMRs was larger in line
      7 2 than in line 6 3, and most of iDMRs found in line 6 3 were overlapped with
      the iDMRs found in line 7 2. We further showed that in vitro methylation levels
      were associated with MDV replication, and found that MDV propagation in the
      infected cells was restricted by pharmacological inhibition of DNA methylation.
      Our results suggest that DNA methylation in the host may be associated with
      disease resistance or susceptibility. The methylation variations induced by viral
      infection may consequentially change the host transcriptome and result in diverse
      disease outcomes. 

PMID- 23538682
TI  - Observing temperature fluctuations in humans using infrared imaging.
AB  - In this work we demonstrate that functional infrared imaging is capable of
      detecting low frequency temperature fluctuations in intact human skin and
      revealing spatial, temporal, spectral, and time-frequency based differences among
      three tissue classes: microvasculature, large sub-cutaneous veins, and the
      remaining surrounding tissue of the forearm. We found that large veins have
      stronger contractility in the range of 0.005-0.06 Hz compared to the other two
      tissue classes. Wavelet phase coherence and power spectrum correlation analysis
      show that microvasculature and skin areas without vessels visible by IR have high
      phase coherence in the lowest three frequency ranges (0.005-0.0095 Hz, 0.0095
      0.02 Hz, and 0.02-0.06 Hz), whereas large veins oscillate independently.

PMID- 23538683
TI  - Dietary fiber and the glycemic index: a background paper for the Nordic Nutrition
      Recommendations 2012.
AB  - The aim of this study is to review recent data on dietary fiber (DF) and the
      glycemic index (GI), with special focus on studies from the Nordic countries
      regarding cardiometabolic risk factors, type 2 diabetes, cardiovascular disease,
      cancer, and total mortality. In this study, recent guidelines and scientific
      background papers or updates on older reports on DF and GI published between 2000
      and 2011 from the US, EU, WHO, and the World Cancer Research Fund were reviewed,
      as well as prospective cohort and intervention studies carried out in the Nordic
      countries. All of the reports support the role for fiber-rich foods and DF as an
      important part of a healthy diet. All of the five identified Nordic papers found
      protective associations between high intake of DF and health outcomes; lower risk
      of cardiovascular disease, type 2 diabetes, colorectal and breast cancer. None of
      the reports and few of the Nordic papers found clear evidence for the GI in
      prevention of risk factors or diseases in healthy populations, although
      association was found in sub-groups, e.g. overweight and obese individuals and
      suggestive for prevention of type 2 diabetes. It was concluded that DF is
      associated with decreased risk of different chronic diseases and metabolic
      conditions. There is not enough evidence that choosing foods with low GI will
      decrease the risk of chronic diseases in the population overall. However, there
      is suggestive evidence that ranking food based on their GI might be of use for
      overweight and obese individuals. Issues regarding methodology, validity and
      practicality of the GI remain to be clarified.

PMID- 23538685
TI  - This month in archives of general psychiatry.

PMID- 23538684
TI  - Heme status affects human hepatic messenger RNA and microRNA expression.
AB  - AIM: To assess effects of heme on messenger RNA (mRNA) and microRNA (miRNA)
      profiles of liver cells derived from humans. METHODS: We exposed human hepatoma
      cell line Huh-7 cells to excess iron protoporphyrin (heme) (10 MUmol/L) or
      induced heme deficiency by addition of 4, 6-dioxoheptanoic acid (500 MUmol/L), a
      potent inhibitor of aminolevulinic acid dehydratase, for 6 h or 24 h. We
      harvested total RNA from the cells and performed both mRNA and miRNA array
      analyses, with use of Affymetrix chips, reagents, and instruments (human genome
      U133 plus 2.0 and miRNA 2.0 arrays). We assessed changes and their significance
      and interrelationships with Target Scan, Pathway Studios, and Ingenuity software.
      RESULTS: Changes in mRNA levels were most numerous and striking at 6 h after heme
      treatment but were similar and still numerous at 24 h. After 6 h of heme
      exposure, the increase in heme oxygenase 1 gene expression was 60-fold by mRNA
      and 88-fold by quantitative reverse transcription-polymerase chain reaction. We
      found striking changes, especially up-regulation by heme of nuclear erythroid-2
      related factor-mediated oxidative stress responses, protein ubiquitination,
      glucocorticoid signaling, P53 signaling, and changes in RNAs that regulate
      intermediary metabolism. Fewer mRNAs were down-regulated by heme, and the fold
      decreases were less exuberant than were the increases. Notable decreases after 24
      h of heme exposure were patatin-like phospholipase domain-containing protein 3 (
      6.5-fold), neuronal PAS domain protein 2 (-1.93-fold), and protoporphyrinogen
      oxidase (-1.7-fold). CONCLUSION: Heme excess exhibits several toxic effects on
      liver and kidney, which deserve study in humans and in animal models of the human
      porphyrias or other disorders.

PMID- 23538686
TI  - Jacob Cohen, PhD, 1923-1998.

PMID- 23538687
TI  - Impact of Family History in Persons With Dual Diagnosis.
AB  - OBJECTIVE: This study examined relationships among family history of alcohol,
      drug, and psychiatric problems and substance use severity, interpersonal
      relationships, and service use in individuals with dual diagnosis. METHODS: Data
      were collected with the family history section of the Addiction Severity Index
      administered as part of three studies of individuals with dual disorders (N=413).
      Participants were categorized into family history risk groups for each problem
      domain based on the number of first and second degree relatives with alcohol,
      drug, or psychiatric problems. RESULTS: Rates of alcohol, drug, and psychiatric
      problems were high across family member categories and highest overall for
      siblings. Over two-thirds of the sample was categorized in the high-risk group in
      the alcohol problem domain, almost half of the sample was categorized as high
      risk in the drug problem domain, and over a third of the sample was categorized
      as high-risk in the psychiatric problem domain. Across problem domains,
      individuals in the high-risk group reported more relationship problems with
      parents and siblings and higher rates of lifetime emotional, physical, and sexual
      abuse than did those in the low or moderate-risk groups. CONCLUSIONS: Family
      history of alcohol, drug, and psychiatric problems is associated with greater
      rates of poor family relationships and history of abuse. Assessment of these
      different forms of family history in multiple family members can aid treatment
      providers in identifying individuals with dual disorders who may benefit from
      trauma-informed care as part of their overall mental health and substance abuse
      treatment services.

PMID- 23538688
TI  - Habitat correlates of the Eurasian otter Lutra lutra recolonizing Central Poland.
AB  - The increase in Eurasian otter Lutra lutra populations in their natural range and
      recolonization processes are recently observed in several European countries. We
      address the process of otter recolonization and habitat utilization in Central
      Poland over 14 years. Field surveys in 1998 and 2007 documented increase in
      occurrence of the species. The frequency of positive sites denoted 15 % in 1993,
      38 % in 1998, and 89 % in 2007. Otter occurrence at study sites was positively
      affected by river width while negatively affected by presence of buildings at the
      site and river regulation. During the most intensive colonization process in the
      1990s, the habitat preferences of the otter did not change. However, the sites
      inhabited by otters after 1998 were characterized by lower river width and tree
      cover and were more often located on regulated river sections, suggesting change
      in habitat tolerance during expansion. The otter abundance in transformed
      habitats is a result of increasing population numbers and the necessity to
      inhabit suboptimal sections of watercourses. Thus, it seems that presence-absence
      data for otter populations cannot be considered a reliable indicator of habitat
      quality, being depended of the population density.

PMID- 23538689
TI  - Slow magnetic relaxation in a cyano-bridged ferromagnetic {Fe(III)Ni(II)}
      alternating chain.
AB  - A cyano-bridged ferromagnetic {Fe(III)Ni(II)} alternating chain
      {[Fe(pzTp)(CN)3][Ni(chxn)2]}.ClO4.H2O (1) (pzTp = tetrakis(pyrazolyl)borate, chxn
      = (1R,2R)-1,2-diaminocyclohexane) was synthesized via rational design. Crystal
      structure analysis and magnetic studies demonstrated that compound had a one
      dimensional zigzagging chain-like structure and slow magnetic relaxation.

PMID- 23538692
TI  - Nox4 as a potential therapeutic target for treatment of uremic toxicity
      associated to chronic kidney disease.
AB  - Watanabe et al. report that Nox4 NADPH oxidase catalytic moiety and the subunit
      p22(phox) mediate the increase in oxidative stress and human tubular epithelial
      cell injury induced by p-cresyl sulfate, a protein-bound uremic toxin. These
      findings could be instrumental for the design of novel therapeutic intervention
      utilizing small-molecule inhibitors specifically targeting Nox oxidases to
      prevent or slow down the progression of chronic kidney disease and the associated
      disorders due to uremic toxicity.

PMID- 23538693
TI  - Toward a bioartificial kidney: will embryonic stem cells be the answer?
AB  - Directing the development of human embryonic stem cells into functional renal
      tubular cells has been limited by the lack of defined, reproducible
      differentiation and culture protocols. If these cells are to be used for in vitro
      testing or therapeutics, viability under bioreactor conditions is required.
      Narayanan et al. describe in detail such methodology. Such knowledge will
      hopefully accelerate the development of the Holy Grail of nephrology, the
      bioartificial kidney.

PMID- 23538694
TI  - Adiponectin: an enlarging role in acute kidney injury.
AB  - Adiponectin (APN) is known as an anti-inflammatory adipokine in obesity and
      atherosclerosis. Jin et al. examine the effects of APN deficiency in renal
      ischemia/reperfusion injury (IRI) using APN knockout mice and demonstrate that
      APN deficiency protects mice from IRI. This newly described role for APN in acute
      kidney injury opens up the possibility of novel mechanistic and therapeutic
      strategies from the cross-fertilization of the fields of obesity and kidney
      diseases.

PMID- 23538695
TI  - The antibacterial shield of the human urinary tract.
AB  - Antibacterial peptides and proteins maintain the sterility of the human urinary
      tract. A broad-spectrum antimicrobial protein, ribonuclease 7 (RNase 7),
      previously discovered to play a role in controlling the growth of bacteria on
      human skin, has now been shown to have an important antibacterial function in the
      human urinary tract.

PMID- 23538696
TI  - Rise or fall of glomerular filtration rate: does it matter?
AB  - A new observational study in Canadian patients shows a U-shaped association
      between longitudinal change in estimated glomerular filtration rate over a 4-year
      period and all-cause mortality. This study confirms the findings of previous
      studies done in middle-aged Taiwanese patients, community-dwelling Medicare
      beneficiaries, and chronic kidney disease patients. Future studies are needed to
      confirm whether such simple objective risk assessment tools can identify
      subgroups of people at maximum risk for adverse events.

PMID- 23538697
TI  - Proton pump inhibitors and hypomagnesemia: a rare but serious complication.
AB  - Proton pump inhibitors (PPIs) promote hypomagnesemia through loss of active
      Mg(2+) absorption via transient receptor potential melastatin-6 and -7 (TRPM6/7).
      Danziger et al. confirm the association of PPIs with hypomagnesemia in patients
      hospitalized at a tertiary medical center. They found that patients taking PPIs,
      compared with those receiving histamine-2 antagonists or no acid-suppressive
      medications, had a decline in serum Mg(2+) after adjusting for several clinical
      and laboratory factors. The effect was seen only in those concomitantly receiving
      diuretics.

PMID- 23538698
TI  - Risk factors that can affect the progression of chronic kidney disease in
      patients with poststreptecoccal glomerulonephritis history.

PMID- 23538699
TI  - The author replies.

PMID- 23538700
TI  - Tadpole cells in an unstained urine sediment.

PMID- 23538701
TI  - The case | Post-tranplant allograft dysfunction.

PMID- 23538702
TI  - Using the DOSE index to predict changes in health status of patients with COPD: a
      prospective cohort study.
AB  - BACKGROUND: The severity of chronic obstructive pulmonary disease (COPD) should
      not be based on the level of airflow limitation alone. A multicomponent index
      such as the DOSE index (dyspnoea score (D), level of airflow obstruction (O),
      current smoking status (S), and exacerbations (E)) has the potential to predict
      important future outcomes in patients with COPD more effectively than the forced
      expiratory volume in one second. Health status deterioration should be prevented
      in COPD patients. AIMS: To investigate whether the DOSE index can predict which
      patients are at risk of a clinically relevant change in health status. METHODS: A
      prospective cohort study was performed using data from primary and secondary
      care. The DOSE score was determined at baseline and the 2-year change in the
      Clinical COPD Questionnaire (CCQ) score was calculated. Linear regression
      analysis was performed for the effect of a high DOSE score (>= 4) on the change
      in CCQ score. RESULTS: The study population consisted of 209 patients (112
      patients from primary care). Overall, a high DOSE score was a significant
      predictor of a change in CCQ score after 2 years (0.41, 95% CI 0.13 to 0.70),
      particularly in primary care patients. CONCLUSIONS: A DOSE score of >= 4 has the
      ability to identify COPD patients with a greater risk of future worsening in
      health status.

PMID- 23538703
TI  - Is spirometry properly used to diagnose COPD? Results from the BOLD study in
      Salzburg, Austria: a population-based analytical study.
AB  - BACKGROUND: Current guidelines recommend spirometry to confirm a diagnosis of
      chronic obstructive pulmonary disease (COPD). AIMS: To investigate whether a self
      reported diagnosis of COPD is associated with prior spirometry and whether a
      correct diagnosis of COPD is more likely when spirometry was performed. METHODS:
      We used data from the population-based Austrian Burden of Obstructive Lung
      Disease (BOLD) study. Participants were aged >40 years and completed post
      bronchodilator spirometry. Reported COPD diagnosis and reported prior lung
      function test were based on questionnaire. Persistent airflow limitation was
      defined as post-bronchodilator forced expiratory volume in one second/forced
      vital capacity ratio <0.7, corresponding with COPD Global initiative for chronic
      Obstructive Lung Disease (GOLD) grade I+, and GOLD grade II+ was also
      investigated. A correct diagnosis of COPD was defined as a reported physician's
      diagnosis of COPD and the presence of persistent airflow limitation. RESULTS: 68
      (5.4%) of 1,258 participants reported a prior physician's diagnosis of COPD. Of
      these, only 17 (25.0%) reported a lung function test within the past 12 months
      and 46 (67.6%) at any time in the past. The likelihood for a correct COPD GOLD
      grade I+ diagnosis was similar among subjects reporting a lung function test
      during the last 12 months (likelihood ratio 2.07, 95% CI 0.89 to 5.50) and those
      not reporting a lung function during the last 12 months (likelihood ratio 2.78,
      95% CI 1.58 to 4.87). Similar likelihood ratios were seen when GOLD grade II+ was
      investigated and when lung function was reported at any time in the past.
      CONCLUSIONS: One-third of subjects with a reported diagnosis of COPD never had a
      lung function test. When spirometry was reported, this did not increase the
      likelihood of a correct COPD diagnosis.

PMID- 23538704
TI  - An orexinergic projection from perifornical hypothalamus to raphe pallidus
      increases rat brown adipose tissue thermogenesis.
AB  - Non-shivering thermogenesis in brown adipose tissue (BAT) plays an important role
      in thermoregulatory cold-defense and, through its metabolic consumption of energy
      reserves to produce heat, can affect the long-term regulation of adiposity. An
      orexinergic pathway from the perifornical lateral hypothalamus (PeF/LH) to the
      rostral raphe pallidus (rRPa) has been demonstrated to increase the gain of the
      excitatory drives to medullary sympathetic premotor neurons controlling BAT
      sympathetic outflow and BAT thermogenesis. With this background, we consider
      neural mechanisms that could underlie orexin's modulation of the excitability of
      BAT sympathetic premotor neurons in rRPa and the potential role of altered BAT
      thermogenesis in pathological conditions associated with the absence of the
      central orexin system. Overall, these new data enhance our understanding of the
      role of central orexin in regulating body temperature and energy homeostasis and
      provide further insight into the neurochemical regulation of BAT thermogenesis
      and metabolism.

PMID- 23538707
TI  - The great east Japan earthquake and tsunami viewed from western Europe: how has
      Fukushima influenced the peaceful use of atomic energy in Europe?

PMID- 23538708
TI  - Caged retinoids as photoinducible activators: implications for cell
      differentiation and neurite outgrowth.
AB  - Aiming to control neurite formation and navigate the axonal growth by an
      extrinsic guidance, we report on the design, synthesis and biological evaluation
      of caged retinoids. Agonists of RARbeta have been temporarily blocked either by
      the [(alpha-methyl-2-nitropiperonyl)oxy]carbonyl (MeNPOC) group or by
      immobilization using nitrocatechol linkers on TiO2 particles. Release on demand
      has been achieved by release under UV irradiation, leading to the biologically
      active compounds, which have been shown to induce neuronal differentiation and
      neurite outgrowth.

PMID- 23538709
TI  - TSH restores a summer phenotype in photoinhibited mammals via the RF-amides RFRP3
      and kisspeptin.
AB  - In mammals, melatonin is the pivotal messenger synchronizing biological
      functions, notably reproductive activity, with annual daylength changes.
      Recently, two major findings clarified melatonin's mode of action. First,
      melatonin controls the production of thyroid stimulating hormone (TSH) by the
      pars tuberalis of the adenohypophysis. This TSH regulates local thyroid hormone
      availability in the mediobasal hypothalamus. Second, the RF-amides kisspeptin and
      RFRP-3, recently discovered regulators of the gonadotropic axis, are involved in
      the melatonin control of reproduction. This study aims to establish a mechanistic
      link between the melatonin-driven TSH and the RF-amide control of reproduction.
      We treated short-day-adapted male Djungarian and Syrian hamsters with a chronic
      central infusion of TSH. In both hamster species, the central administration of 5
      mIU/d TSH for 4 to 6 wk restored the summer phenotype of both testicular activity
      and kisspeptin and RFRP expression. Vehicle treated hamsters remain sexually
      inactive. Furthermore, the TSH treatment increased the body weight of lean short
      day-adapted Djungarian hamsters and reduced hypothalamic somatostatin expression
      to the summer phenotype. In summary, our study demonstrates the pivotal role of
      melatonin-driven TSH for the seasonal regulation of reproduction and body weight,
      and uncovers the neuropeptides relaying this signal within the hypothalamus.

PMID- 23538710
TI  - Paternal lifestyle as a potential source of germline mutations transmitted to
      offspring.
AB  - Paternal exposure to high levels of radioactivity causes heritable germline
      minisatellite mutations. However, the effect of more general paternal exposures,
      such as cigarette smoking, on germline mutations remains unexplored. We analyzed
      two of the most commonly used minisatellite loci (CEB1 and B6.7) to identify
      germline mutations in blood samples of complete mother-father-child triads from
      the Norwegian Mother and Child Cohort Study (MoBa). The presence of mutations was
      subsequently related to general lifestyle factors, including paternal smoking
      before the partner became pregnant. Paternally derived mutations at the B6.7
      locus (mutation frequency 0.07) were not affected by lifestyle. In contrast, high
      gross yearly income as a general measure of a healthy lifestyle coincided with
      low-mutation frequencies at the CEB1 locus (P=0.047). Income was inversely
      related to smoking behavior, and paternally derived CEB1 mutations were dose
      dependently increased when the father smoked in the 6 mo before pregnancy, 0.21
      vs. 0.05 in smoking and nonsmoking fathers, respectively (P=0.061). These results
      suggest that paternal lifestyle can affect the chance of heritable mutations in
      unstable repetitive DNA sequences. To our knowledge, this is the first study
      reporting an effect of lifestyle on germline minisatellite mutation frequencies
      in a human population with moderate paternal exposures.

PMID- 23538711
TI  - Simultaneously defining cell phenotypes, cell cycle, and chromatin modifications
      at single-cell resolution.
AB  - Heterogeneity of cellular phenotypes in asynchronous cell populations placed in
      the same biochemical and biophysical environment may depend on cell cycle and
      chromatin modifications; however, no current method can measure these properties
      at single-cell resolution simultaneously and in situ. Here, we develop, test, and
      validate a new microscopy assay that rapidly quantifies global acetylation on
      histone H3 and measures a wide range of cell and nuclear properties, including
      cell and nuclear morphology descriptors, cell-cycle phase, and F-actin content of
      thousands of cells simultaneously, without cell detachment from their substrate,
      at single-cell resolution. These measurements show that isogenic, isotypic cells
      of identical DNA content and the same cell-cycle phase can still display large
      variations in H3 acetylation and that these variations predict specific
      phenotypic variations, in particular, nuclear size and actin cytoskeleton
      content, but not cell shape. The dependence of cell and nuclear properties on
      cell-cycle phase is assessed without artifact-prone cell synchronization. To
      further demonstrate its versatility, this assay is used to quantify the complex
      interplay among cell cycle, epigenetic modifications, and phenotypic variations
      following pharmacological treatments affecting DNA integrity, cell cycle, and
      inhibiting chromatin-modifying enzymes.

PMID- 23538713
TI  - A population-based study of fall risk factors among people with multiple
      sclerosis in Stockholm county.
AB  - OBJECTIVE: To identify factors associated with increased likelihood of reporting
      a recent fall among people with multiple sclerosis. This study was exploratory in
      its intent to examine sense of coherence as a contextual influence on fall risk.
      The study also sought to confirm that variables previously identified as fall
      risk factors for people with multiple sclerosis persist when tested in a
      population-based sample. DESIGN: The study was cross-sectional and data was
      obtained in the context of a population-based study of people with multiple
      sclerosis living in Stockholm. SUBJECTS: A total of 164 people with multiple
      sclerosis, age range 19-79 years. METHODS: Data were gathered through established
      instruments. Key instruments utilized included the sense of coherence scale, the
      Lindmark Motor Capacity Assessment's subscale for balance, and the 10-metre
      walking test. A logistic regression model examined factors associated with
      reporting a fall in the past 3 months. RESULTS: Of the participants, 62 (38%)
      reported experiencing at least one fall in the past 3 months. Reduced walking
      speed, impaired balance, and weak sense of coherence were associated with falls
      in the past 3 months. CONCLUSION: These findings underscore the importance of
      examining diverse and modifiable influences on fall risk, including walking
      speed, balance and sense of coherence, in future studies involving people with
      multiple sclerosis.

PMID- 23538715
TI  - RK2 plasmid dynamics in Caulobacter crescentus cells--two modes of DNA
      replication initiation.
AB  - Undisturbed plasmid dynamics is required for the stable maintenance of plasmid
      DNA in bacterial cells. In this work, we analysed subcellular localization, DNA
      synthesis and nucleoprotein complex formation of plasmid RK2 during the cell
      cycle of Caulobacter crescentus. Our microscopic observations showed asymmetrical
      distribution of plasmid RK2 foci between the two compartments of Caulobacter
      predivisional cells, resulting in asymmetrical allocation of plasmids to progeny
      cells. Moreover, using a quantitative PCR (qPCR) method, we estimated that
      multiple plasmid particles form a single fluorescent focus and that the number of
      plasmids per focus is approximately equal in both swarmer and predivisional
      Caulobacter cells. Analysis of the dynamics of TrfA-oriV complex formation during
      the Caulobacter cell cycle revealed that TrfA binds oriV primarily during the G1
      phase, however, plasmid DNA synthesis occurs during the S and G2 phases of the
      Caulobacter cell cycle. Both in vitro and in vivo analysis of RK2 replication
      initiation in C. crescentus cells demonstrated that it is independent of the
      Caulobacter DnaA protein in the presence of the longer version of TrfA protein,
      TrfA-44. However, in vivo stability tests of plasmid RK2 derivatives suggested
      that a DnaA-dependent mode of plasmid replication initiation is also possible.

PMID- 23538714
TI  - Buccals are likely to be a more informative surrogate tissue than blood for
      epigenome-wide association studies.
AB  - There is increasing evidence that interindividual epigenetic variation is an
      etiological factor in common human diseases. Such epigenetic variation could be
      genetic or non-genetic in origin, and epigenome-wide association studies (EWASs)
      are underway for a wide variety of diseases/phenotypes. However, performing an
      EWAS is associated with a range of issues not typically encountered in genome
      wide association studies (GWASs), such as the tissue to be analyzed. In many
      EWASs, it is not possible to analyze the target tissue in large numbers of live
      humans, and consequently surrogate tissues are employed, most commonly blood. But
      there is as yet no evidence demonstrating that blood is more informative than
      buccal cells, the other easily accessible tissue. To assess the potential of
      buccal cells for use in EWASs, we performed a comprehensive analysis of a buccal
      cell methylome using whole-genome bisulfite sequencing. Strikingly, a buccal vs.
      blood comparison reveals>6X as many hypomethylated regions in buccal. These
      tissue-specific differentially methylated regions (tDMRs) are strongly enriched
      for DNaseI hotspots. Almost 75% of these tDMRs are not captured by commonly used
      DNA methylome profiling platforms such as Reduced Representational Bisulfite
      Sequencing and the Illumina Infinium HumanMethylation450 BeadChip, and they also
      display distinct genomic properties. Buccal hypo-tDMRs show a statistically
      significant enrichment near SNPs associated to disease identified through GWASs.
      Finally, we find that, compared with blood, buccal hypo-tDMRs show significantly
      greater overlap with hypomethylated regions in other tissues. We propose that for
      non-blood based diseases/phenotypes, buccal will be a more informative tissue for
      EWASs. 

PMID- 23538716
TI  - The RpfCG two-component system negatively regulates the colonization of sugar
      cane stalks by Xanthomonas albilineans.
AB  - The genome of Xanthomonas albilineans, the causal agent of sugar cane leaf scald,
      carries a gene cluster encoding a predicted quorum sensing system that is highly
      related to the diffusible signalling factor (DSF) systems of the plant pathogens
      Xylella fastidiosa and Xanthomonas campestris. In these latter pathogens, a
      cluster of regulation of pathogenicity factors (rpf) genes encodes the DSF system
      and is involved in control of various cellular processes. Mutation of Xanthomonas
      albilineans rpfF, encoding a predicted DSF synthase, in Florida strain XaFL07-1
      resulted in a small reduction of disease severity (DS). Single-knockout mutations
      of rpfC and rpfG (encoding a predicted DSF sensor and regulator, respectively)
      had no effect on DS or swimming motility of the pathogen. However, capacity of
      the pathogen to cause disease was slightly reduced and swimming motility was
      severely affected when rpfG and rpfC were both deleted. Similar results were
      obtained when the entire rpfGCF region was deleted. Surprisingly, when the
      pathogen was mutated in rpfG or rpfC (single or double mutations) it was able to
      colonize sugar cane spatially more efficiently than the wild-type. Mutation in
      rpfF alone did not affect the degree of spatial invasion. We conclude that the
      DSF signal contributes to symptom expression but not to invasion of sugar cane
      stalks by Xanthomonas albilineans strain XaFL07-1, which is mainly controlled by
      the RpfCG two-component system.

PMID- 23538717
TI  - Strong composite films with layered structures prepared by casting silk fibroin
      graphene oxide hydrogels.
AB  - Composite films of graphene oxide (GO) sheets and silk fibroin (SF) with layered
      structures have been prepared by facile solution casting of SF-GO hydrogels. The
      as-prepared composite film containing 15% (by weight, wt%) of SF shows a high
      tensile strength of 221 +/- 16 MPa and a failure strain of 1.8 +/- 0.4%, which
      partially surpass those of natural nacre. Particularly, this composite film also
      has a high modulus of 17.2 +/- 1.9 GPa. The high mechanical properties of this
      composite film can be attributed to its high content of GO (85 wt%), compact
      layered structure and the strong hydrogen bonding interaction between SF chains
      and GO sheets.

PMID- 23538718
TI  - Phase modulation of thermotropic liquid crystals of tetra-n-alkylammonium
      polyoxometalate ionic complexes.
AB  - A series of composition analogous polyoxometalate-based ionic complexes are
      synthesized and studied, with a focus on the correlation between their
      mesomorphic behavior and their chemical structure. Generally, these polarizable
      rigid polyoxoanion clusters decorated with hydrophobic flexible alkyl chains have
      demonstrated a propensity to form thermotropic liquid-crystalline (LC) phases.
      Characterized by differential scanning calorimetry (DSC), polarized optical
      microscopy (PM), and X-ray diffraction (XRD), two of the four investigated
      complexes tend to form thermodynamically stable mesophases. Longer alkyl chains
      have been found to form mesophases, and the alkyl chain length of the quaternary
      ammonium cations influences both the occurrence and type of mesophase exhibited.

PMID- 23538719
TI  - Methotrexate vs azathioprine in second-line therapy of sarcoidosis.
AB  - BACKGROUND: Steroids remain the first-choice therapeutic in sarcoidosis; however,
      long-term use is associated with toxicity. Evidence defining the best second-line
      therapeutic is currently lacking. The aim of this study was to compare the effect
      of methotrexate and azathioprine on prednisone tapering, pulmonary function, and
      side effects in the second-line treatment of sarcoidosis. METHODS: An
      international retrospective cohort study was performed, reviewing all patients
      with sarcoidosis who started methotrexate or azathioprine until 2 years after
      initiation or discontinuation. A linear mixed model with FEV1, vital capacity
      (VC), diffusing capacity of lung for carbon monoxide (DLCO), and prednisone dose
      changes over time as end points was used. Side effects were compared with chi2
      tests. RESULTS: Two hundred patients were included, of whom 145 received
      methotrexate and 55 azathioprine. Prednisone daily dose decreased a mean of 6.32
      mg/y (P < .0001) while on therapy, with a similar steroid-sparing capacity for
      methotrexate and azathioprine. Of all patients completing 1 year of therapy, 70%
      had a reduction in daily prednisone dose of at least 10 mg. FEV1 showed a mean
      increase of 52 mL/y (P = .006) and VC of 95 mL/y (P = .001) in both treatment
      groups. DLCO % predicted increased, with a mean of 1.23%/y (P = .018). There were
      more patients with infections in the azathioprine group (34.6% vs 18.1%, P =
      .01), but no differences regarding other side effects. CONCLUSIONS: This
      retrospective study comparing the effect of second-line therapy in sarcoidosis
      shows that both methotrexate and azathioprine have significant steroid-sparing
      potency, a similar positive effect on lung function, and comparable side effects,
      except for a higher infection rate in the azathioprine group.

PMID- 23538720
TI  - Total synthesis and biological evaluation of (-)-exiguolide analogues: importance
      of the macrocyclic backbone.
AB  - (-)-Exiguolide (1), isolated from the marine sponge Geodia exigua, has been shown
      to inhibit the growth of the A549 human lung adenocarcinoma and NCI-H460 human
      lung large cell carcinoma cells in vitro. In this study, we synthesized
      structural analogues of 1 to explore its skeletal structure-activity
      relationships and found that the C18 methyl group and the configuration of the
      C16-C17 double bond of 1 are important for the potent antiproliferative activity.
      Furthermore, we prepared a series of side-chain analogues of 1 by diversification
      of a late-stage intermediate of our total synthesis, and found that the triene
      side chain of 1 could be modified to some extent without significant loss of
      activity, provided a Lewis basic heteroatom is placed at the terminus.

PMID- 23538721
TI  - Use of electronic medical records differs by specialty and office settings.
AB  - OBJECTIVE: To assess differences in the use of electronic medical records (EMRs)
      among medical specialties and practice settings. METHODS: A cross-sectional
      retrospective study using nationally representative data from the National
      Ambulatory Medical Care Survey for the period 2003-2010 was performed. Bivariate
      and multivariate analyzes compared EMR use among physicians of 14 specialties and
      assessed variation by practice setting. Differences in EMR use by geographic
      region, patient characteristics, and physician office settings were also
      assessed. RESULTS: Bivariate and multivariate analysis demonstrated increased EMR
      use from 2003 to 2010, with 16% reporting at least partial use in 2003, rising to
      52% in 2010 (p<0.001). Cardiologists, orthopedic surgeons, urologists, and
      family/general practitioners had higher frequencies of EMR use whereas
      psychiatrists, ophthalmologists, and dermatologists had the lowest EMR use.
      Employed physicians had higher EMR uptake than physicians who owned their
      practice (48% vs 31%, p<0.001). EMR uptake was lower among solo practitioners
      (23%) than non-solo practitioners (42%, p<0.001). Practices owned by Health
      Maintenance Organizations had higher frequencies of EMR use (83%) than practices
      owned by physicians, community health centers, or academic centers (all <45%,
      p<0.001). Patient demographics did not affect EMR use (p>0.05). CONCLUSIONS:
      Uptake of EMR is increasing, although it is significantly slower in dermatology,
      ophthalmology, and psychiatry. Solo practitioners and owners of a practice have
      low frequencies of EMR use compared with non-solo practitioners and those who do
      not own their practice. Despite incentives for EMR adoption, physicians should
      carefully weigh which, if any, EMR to adopt in their practices.

PMID- 23538722
TI  - Development of a 5 year life expectancy index in older adults using predictive
      mining of electronic health record data.
AB  - OBJECTIVE: Incorporating accurate life expectancy predictions into clinical
      decision making could improve quality and decrease costs, but few providers do
      this. We sought to use predictive data mining and high dimensional analytics of
      electronic health record (EHR) data to develop a highly accurate and clinically
      actionable 5 year life expectancy index. MATERIALS AND METHODS: We developed the
      index using EHR data for 7463 patients >=50 years old with >=1 visit(s) in 2003
      to a large, academic, multispecialty group practice. We extracted 980 attributes
      from the EHRs of the practices and affiliated hospitals. Correlation feature
      selection with greedy stepwise search was used to find the attribute subset with
      best average merit. Rotation forest ensembling with alternating decision tree as
      underlying classifier was used to predict 5 year mortality. Model performance was
      compared with the modified Charlson Comorbidity Index and the Walter life
      expectancy method. RESULTS: Within 5 years of the last visit in 2003, 838 (11%)
      patients had died. The final model included 24 attributes: two demographic (age,
      sex), 10 comorbidity (eg, cardiovascular disease), one vital sign (mean diastolic
      blood pressure), two medications (loop diuretic use, digoxin use), six laboratory
      (eg, mean albumin), and three healthcare utilization (eg, the number of
      hospitalizations 1 year prior to the last visit in 2003). The index showed very
      good discrimination (c-statistic 0.86) and outperformed comparators. CONCLUSIONS:
      The EHR based index successfully distinguished adults >=50 years old with life
      expectancy >5 years from those with life expectancy <=5 years. This information
      could be used clinically to optimize preventive service use (eg, cancer screening
      in the elderly).

PMID- 23538723
TI  - The wave has finally broken: now what?
AB  - In 2005, the authors published a paper, 'Will the wave finally break? A brief
      view of the adoption of electronic medical records in the United States', which
      predicted that rapid adoption of electronic health records (EHR) would occur in
      the next 5 years given appropriate incentives. The wave has finally broken with
      the stimulus of the health information technology for economic and clinical
      health legislation in 2009, and there have been both positive and negative
      developments in the ensuing years. The positive developments, among others
      described, are increased adoption of EHR, the emergence of a national network
      infrastructure and the recognition of clinical informatics as a medical
      specialty. Problems that still exist include, among others described, continued
      user interface problems, distrust of EHR-generated notes and an increased
      potential for fraud and abuse. It is anticipated that in the next 5 years there
      will be near universal EHR adoption, greater emphasis on standards and
      interoperability, greater involvement of Congress in health information
      technology (IT), breakthroughs in user interfaces, compelling online medical and
      IT education, both increased use of data analytics for personalized healthcare
      and a realization of the difficulties of this approach, a blurring of the
      distinction between EHR and telemedicine, a resurgence of computer-assisted
      diagnosis and the emergence of a 'continuously learning' healthcare system.

PMID- 23538724
TI  - Patient-centered care requires a patient-oriented workflow model.
AB  - Effective design of health information technology (HIT) for patient-centered care
      requires consideration of workflow from the patient's perspective, termed
      'patient-oriented workflow.' This approach organizes the building blocks of work
      around the patients who are moving through the care system. Patient-oriented
      workflow complements the more familiar clinician-oriented workflow approaches,
      and offers several advantages, including the ability to capture simultaneous,
      cooperative work, which is essential in care delivery. Patient-oriented workflow
      models can also provide an understanding of healthcare work taking place in
      various formal and informal health settings in an integrated manner. We present
      two cases demonstrating the potential value of patient-oriented workflow models.
      Significant theoretical, methodological, and practical challenges must be met to
      ensure adoption of patient-oriented workflow models. Patient-oriented workflow
      models define meaningful system boundaries and can lead to HIT implementations
      that are more consistent with cooperative work and its emergent features.

PMID- 23538725
TI  - Automatic glaucoma diagnosis through medical imaging informatics.
AB  - BACKGROUND: Computer-aided diagnosis for screening utilizes computer-based
      analytical methodologies to process patient information. Glaucoma is the leading
      irreversible cause of blindness. Due to the lack of an effective and standard
      screening practice, more than 50% of the cases are undiagnosed, which prevents
      the early treatment of the disease. OBJECTIVE: To design an automatic glaucoma
      diagnosis architecture automatic glaucoma diagnosis through medical imaging
      informatics (AGLAIA-MII) that combines patient personal data, medical retinal
      fundus image, and patient's genome information for screening. MATERIALS AND
      METHODS: 2258 cases from a population study were used to evaluate the screening
      software. These cases were attributed with patient personal data, retinal images
      and quality controlled genome data. Utilizing the multiple kernel learning-based
      classifier, AGLAIA-MII, combined patient personal data, major image features, and
      important genome single nucleotide polymorphism (SNP) features. RESULTS AND
      DISCUSSION: Receiver operating characteristic curves were plotted to compare
      AGLAIA-MII's performance with classifiers using patient personal data, images,
      and genome SNP separately. AGLAIA-MII was able to achieve an area under curve
      value of 0.866, better than 0.551, 0.722 and 0.810 by the individual personal
      data, image and genome information components, respectively. AGLAIA-MII also
      demonstrated a substantial improvement over the current glaucoma screening
      approach based on intraocular pressure. CONCLUSIONS: AGLAIA-MII demonstrates for
      the first time the capability of integrating patients' personal data, medical
      retinal image and genome information for automatic glaucoma diagnosis and
      screening in a large dataset from a population study. It paves the way for a
      holistic approach for automatic objective glaucoma diagnosis and screening.

PMID- 23538726
TI  - The increases in mRNA expressions of inflammatory cytokines by adding cleaning
      solvent or tetrachloroethylene in the murine macrophage cell line J774.1
      evaluated by real-time PCR.
AB  - The use of a petroleum-derived cleaning solvent for dry cleaning, instead of
      tetrachloroethylene (perchloroethylene, PCE), has increased. The cleaning solvent
      may induce immunological alteration. In this study, murine macrophage-lineage
      J774.1 cells were exposed to the cleaning solvent at 0, 25, 50, and 75 ug/ml or
      PCE at 0, 400, 600, 800, and 1,000 ug/ml by vigorous vortexing. Cell viability
      was determined. The mRNA expressions of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1beta), IL-6, IL-10, IL-12p40 (a dimer of IL-12), and IL
      27p28 (a dimer of IL-27) were evaluated by real-time PCR. The mean viabilities in
      the 50 and 75 ug/ml groups of the cleaning solvent were significantly lower than
      that of the control. The mean mRNA expressions of TNF-alpha and IL-1beta in the
      50 ug/ml group were significantly higher than those in the control. For PCE, the
      mean viabilities at 600 ug/ml and over were significantly lower than that of the
      control. The mean expressions of IL-6 and IL-10 in the 800 ug/ml group were
      significantly higher than that in the control. The productions of IL-1beta and
      TNF-alpha may be altered in human during intoxication of the cleaning solvent as
      well as those of IL-6 and IL-10 in human during that of PCE, and these may affect
      on immune cells.

PMID- 23538727
TI  - Ion exchange chromatography and mass spectrometric methods for analysis of
      cadmium-phytochelatin (II) complexes.
AB  - In this study, in vitro formed Cd-phytochelatin (PC2) complexes were
      characterized using ion exchange chromatography (IEC) and matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The ratio of
      both studied compounds as well as experimental conditions were optimized. The
      highest yield of the complex was observed under an applied concentration of 100
      ug.mL(-1) PC2 and 100 ug.mL(-1) of CdCl2. The data obtained show that IEC in
      combination with MALDI-TOF is a reliable and fast method for the determination of
      these complexes.

PMID- 23538728
TI  - Food fortification and decline in the prevalence of neural tube defects: does
      public intervention reduce the socioeconomic gap in prevalence?
AB  - OBJECTIVE: A significant decline in the prevalence of neural tube defects (NTD)
      through food fortification has been reported. Questions remain, however, about
      the effectiveness of this intervention in reducing the gap in prevalence across
      socioeconomic status (SES). STUDY DESIGN: Using health number and through record
      linkage, children born in Ontario hospitals between 1994 and 2009 were followed
      for the diagnosis of congenital anomalies. SES quintiles were assigned to each
      child using census information at the time of birth. Adjusted rates and
      multivariate models were used to compare trends among children born in different
      SES groups. RESULTS: Children born in low SES areas had significantly higher
      rates of NTDs (RR = 1.25, CI: 1.14-1.37). Prevalence of NTDs among children born
      in low and high SES areas declined since food fortification began in 1999
      although has started rising again since 2006. While the crude decline was greater
      in low SES areas, after adjustment for maternal age, the slope of decline and SES
      gap in prevalence rates remained unchanged overtime. CONCLUSIONS: While food
      fortification is successful in reducing the prevalence of NTDs, it was not
      associated with removing the gap between high and low SES groups.

PMID- 23538729
TI  - Welfare state regimes, gender, and depression: a multilevel analysis of middle
      and high income countries.
AB  - Using the 2002 World Health Survey, we examine the association between welfare
      state regimes, gender and mental health among 26 countries classified into seven
      distinct regimes: Conservative, Southeast Asian, Eastern European, Latin
      American, Liberal, Southern/Ex-dictatorship, and Social Democratic. A two-level
      hierarchical model found that the odds of experiencing a brief depressive episode
      in the last 12 months was significantly higher for Southern/Ex- dictatorship
      countries than for Southeast Asian (odds ratio (OR) = 0.12, 95% confidence
      interval (CI) 0.05-0.27) and Eastern European (OR = 0.36, 95% CI 0.22-0.58)
      regimes after controlling for gender, age, education, marital status, and
      economic development. In adjusted interaction models, compared to Southern/Ex
      dictatorship males (reference category), the odds ratios of depression were
      significantly lower among Southeast Asian males (OR = 0.16, 95% CI 0.08-0.34) and
      females (OR = 0.23, 95% CI 0.10-0.53) and Eastern European males (OR = 0.41, 95%
      CI 0.26-0.63) and significantly higher among females in Liberal (OR = 2.00, 95%
      CI 1.14-3.49) and Southern (OR = 2.42, 95% CI 1.86-3.15) regimes. Our results
      highlight the importance of incorporating middle-income countries into
      comparative welfare regime research and testing for interactions between welfare
      regimes and gender on mental health.

PMID- 23538730
TI  - A comparison of willingness to pay to prevent child maltreatment deaths in
      Ecuador and the United States.
AB  - Estimating the benefits of preventing child maltreatment (CM) is essential for
      policy makers to determine whether there are significant returns on investment
      from interventions to prevent CM. The aim of this study was to estimate the
      benefits of preventing CM deaths in an Ecuadorian population, and to compare the
      results to a similar study in a US population. The study used the contingent
      valuation method to elicit respondents' willingness to pay (WTP) for a 1 in
      100,000 reduction in the risk of CM mortality. After adjusting for differences in
      purchasing power, the WTP to prevent the CM mortality risk reduction in the
      Ecuador population was $237 and the WTP for the same risk reduction in the US
      population was $175. In the pooled analysis, WTP for a reduction in CM mortality
      was significantly impacted by country (p = 0.03), history of CM (p = 0.007),
      payment mechanism (p < 0.001), confidence in response (p = 0.014), and
      appropriateness of the payment mechanism (p < 0.001). These findings suggest that
      estimating benefits from one culture may not be transferable to another, and that
      low- and middle-income countries, such as Ecuador, may be better served by
      developing their own benefits estimates for use in future benefit-cost analyses
      of interventions designed to prevent CM.

PMID- 23538731
TI  - Quadruple primary malignancy patient with survival time more than 20 years.
AB  - Multiple primary carcinoma (MPC) is defined as two or more carcinomas without
      subordinate relationship detected in the same or other organs of an individual
      patient. The diagnosis of MPC must comply with the following standards: each of
      the tumors must present a definite picture of malignancy, each tumor must be
      histologically distinct, and the probability of one being a metastasis of the
      other must be excluded. MPC often occurs in the digestive system, but its
      pathogenesis remains unclear involving genetic susceptibility, tumor immunity and
      iatrogenic factors, including radiotherapy and chemotherapy. Most MPC patients
      are double primary malignancy; the occurrence of quadruple primary malignancy is
      below 0.1%. Here we present a rare case of quadruple primary malignancy involving
      the small intestine, descending colon, renal pelvis and pancreas. Due to its
      rarity, the relevant literature is also reviewed. In general, the incidence of
      MPC is rising, so prevention, early diagnosis and treatment will become necessary
      and important. Therefore, further research should focus on the etiology and
      mechanism of MPC.

PMID- 23538732
TI  - Bilateral interstitial keratitis and granulomatous uveitis of tubercular origin.
AB  - BACKGROUND: Tuberculosis (TB) is an important cause of ocular morbidity.
      Establishing a diagnosis may be difficult in some situations especially with
      unusual presentation. We report case of bilateral interstitial keratitis (IK)
      associated with anterior uveitis as a presenting feature of ocular TB from India.
      METHODS: A 17-year-old woman presented with diminution of vision in both eyes.
      Slit lamp biomicroscopy showed central bilateral IK and active granulomatous
      uveitis. Laboratory investigations revealed raised erythrocyte sedimentation rate
      (50 mm/hr) and positive tuberculin test (22 mm induration) and QuantiFERON-TB
      Gold test (3.34 IU/mL), with no foci of systemic infection. RESULTS: Presumptive
      diagnosis of ocular TB was made. The patient was started on antitubercular
      therapy and topical steroids, after which symptoms and signs resolved. There was
      no recurrence of the disease for 1 year after completion of antitubercular
      therapy. CONCLUSIONS: Bilateral central IK with granulomatous uveitis is probably
      related to the presence of tubercular antigen in aqueous humor. Positive
      QuantiFERON-TB Gold test is useful for initiating the antitubercular treatment
      where unusual presentation is encountered.

PMID- 23538734
TI  - Improving interobserver variation in corneal sublayer pachymetry using ConfoScan4
      with z ring.
AB  - OBJECTIVES: To observe and improve the interobserver variation of corneal
      sublayer pachymetry using ConfoScan4 (CS4) z ring. METHODS: Right corneas of 34
      normal subjects were scanned using CS4 (z ring) (Nidek Technologies, Padova,
      Italy). Corneal sublayer pachymetry was performed by two masked observers based
      on the written frame selection criteria from literature. The full stromal
      thickness (FST), epithelial and Bowman layer thickness (Epi+BT), endothelial
      thickness (EndoT), and total corneal thickness (CT) were obtained. Upon
      completion of the measurements (measurement 1), the frame selection criteria were
      reviewed between the observers by going through some corneal frames together.
      Eight subjects were excluded and corneal sublayer pachymetry was re-evaluated by
      the two observers using the revised criteria (measurement 2). RESULTS: Corneal
      thickness showed significant interobserver difference in measurement 1 (n=34),
      but no significant difference in measurement 2 (n=26). Endothelial thickness
      remained significant difference between observers throughout the study.
      Interobserver difference significantly reduced using the revised criteria in CT
      (1.93 +/- 3.23 MUm to 0.28 +/- 1.75 MUm) and EndoT (4.01 +/- 4.82 MUm to 0.86 +/-
      1.81MUm). There was no significant difference between observers in Epi+BT and FST
      for the two measurements. Interobserver variation and the 95% confidence limits
      between observers for CT and corneal sublayers were reduced at least by half in
      measurement 2. CONCLUSIONS: The interobserver variation in corneal sublayer
      pachymetry could be improved by having the observers going through some corneal
      frames together rather than just following the written criteria. The use of CS4
      (z ring) to measure CT, FST, and Epi+BT is suitable for monitoring corneal
      changes clinically.

PMID- 23538733
TI  - Resolution of slit-lamp microscopy photography using various cameras.
AB  - PURPOSE: To evaluate the resolutions of slit-lamp microscopy photography using
      various cameras. DESIGN: Evaluation of diagnostic test or technology.
      PARTICIPANTS: Healthy subjects were imaged with these adapted cameras through
      slit-lamp microscopy. METHODS: A total of 8 cameras, including 6 custom-mounted
      slit-lamp cameras and 2 commercial slit-lamp cameras, were tested with standard
      slit-lamp microscopy devices for imaging of the eye. Various magnifications were
      used during imaging. A standard resolution test plate was used to test the
      resolutions at different magnifications. These outcomes were compared with
      commercial slit-lamp cameras. MAIN OUTCOME MEASURES: The main measurements
      included the display spatial resolutions, image spatial resolutions, and ocular
      resolutions. The outcome also includes the relationships between resolution and
      the pixel density of the displays and images. RESULTS: All cameras were
      successfully adapted to the slit-lamp microscopy, and high-quality ocular images
      were obtained. Differences in the display spatial resolutions were found among
      cameras [analysis of variance (ANOVA), P<0.05]. Higher display resolutions were
      found with cameras using the high-definition multimedia interface (HDMI) compared
      with others, including cameras in smart phones. The display resolutions of smart
      phone displays were greater than cameras with video graphics array displays. The
      display spatial resolutions were found as a function of display pixel density
      (r>0.95, P<0.05) and magnification (r>0.85, P<0.05). Different image spatial
      resolutions were found among cameras (ANOVA, P<0.05) as a function of image pixel
      density (r>0.98, P<0.05) and magnification (r>0.85, P<0.05). The commercial
      slitlamp with a single lens reflex camera yielded the highest image spatial
      resolution. However, the ocular resolution through binocular viewing of the slit
      lamp microscopy was found to have the highest resolution compared with the
      display and image spatial resolutions of all of the cameras. CONCLUSIONS: Several
      cameras can be adapted with slit-lamp microscopy for ophthalmic imaging, yielding
      various display and image spatial resolutions. However, the resolution seemed to
      not be as good as ocular viewing through the slit-lamp biomicroscope.

PMID- 23538735
TI  - Science writing competition: Hip, hip, hooray!
AB  - X-rays are best known for showing where bones have fractured, but researchers can
      also use X-rays to investigate why bones break, which could lead to treatments
      that reduce the number of elderly people who suffer broken hips.

PMID- 23538736
TI  - Accelerated evolution of innate immunity proteins in social insects: adaptive
      evolution or relaxed constraint?
AB  - The genomes of eusocial insects have a reduced complement of immune genes-an
      unusual finding considering that sociality provides ideal conditions for disease
      transmission. The following three hypotheses have been invoked to explain this
      finding: 1) social insects are attacked by fewer pathogens, 2) social insects
      have effective behavioral or 3) novel molecular mechanisms for combating
      pathogens. At the molecular level, these hypotheses predict that canonical innate
      immune pathways experience a relaxation of selective constraint. A recent study
      of several innate immune genes in ants and bees showed a pattern of accelerated
      amino acid evolution, which is consistent with either positive selection or a
      relaxation of constraint. We studied the population genetics of innate immune
      genes in the honey bee Apis mellifera by partially sequencing 13 genes from the
      bee's Toll pathway (~10.5 kb) and 20 randomly chosen genes (~16.5 kb) sequenced
      in 43 diploid workers. Relative to the random gene set, Toll pathway genes had
      significantly higher levels of amino acid replacement mutations segregating
      within A. mellifera and fixed between A. mellifera and A. cerana. However, levels
      of diversity and divergence at synonymous sites did not differ between the two
      gene sets. Although we detect strong signs of balancing selection on the pathogen
      recognition gene pgrp-sa, many of the genes in the Toll pathway show signatures
      of relaxed selective constraint. These results are consistent with the reduced
      complement of innate immune genes found in social insects and support the
      hypothesis that some aspect of eusociality renders canonical innate immunity
      superfluous.

PMID- 23538737
TI  - Mapping patient goals to the International Classification of Functioning,
      Disability and Health (ICF): examining the content validity of the low back pain
      core sets.
AB  - OBJECTIVE: To determine whether the International Classification of Functioning,
      Disability and Health (ICF) Low Back Pain Core Sets are sufficient to cover the
      activity and participation goals that patients prioritize when commencing
      multidisciplinary rehabilitation. DESIGN: Prospective multi-site cross-sectional
      questionnaire study. SUBJECTS: Patients with chronic low back pain attending
      multidisciplinary outpatient clinics at two metropolitan hospitals in Australia.
      METHODS: Participants used the Patient Specific Functional Scale to record goals
      when commencing rehabilitation. Two raters employed a standardized procedure to
      extract and link goal concepts to the ICF. A description exploration was
      undertaken with reference to the low back pain Core Sets. Sample size was
      determined via saturation. RESULTS: Saturation was achieved with 33 participants.
      Ninety five goals were identified, from which 109 concepts were extracted. All of
      the concepts could be linked to the ICF, spanning 23 2nd-level categories. The
      comprehensive and brief core sets encompassed 95% and 65% of the concepts
      respectively. Maintaining body position (d415), doing housework (d640), changing
      basic body position (d410) and walking (d450) accounted for the majority (50.5%)
      of goals. CONCLUSION: This study confirms the content validity of the low back
      pain Core Sets from the patients' perspective. The Core Sets are likely to have
      good clinical utility, however, additional research is required to substantiate
      whether ratings of ICF based goals can be used to measure goal achievement.

PMID- 23538738
TI  - Recommendations and the state of the evidence for physical activity interventions
      for adults with rheumatoid arthritis: 2007 to present.
AB  - Patients with rheumatoid arthritis (RA) are twice as likely as their healthy
      peers to suffer from cardiovascular disease. RA is also a major cause of
      disability and reduced quality of life. Clinical trials of exercise and physical
      activity interventions demonstrate positive effects on muscle strength, function,
      aerobic capacity, mood and disability. While RA management guidelines emphasize
      the role of exercise and physical activity in the management of RA, the
      description of physical activity and exercise is vague and patients with RA
      remain less physically active than their healthy counterparts. This review
      discusses the benefits of physical activity and current physical activity
      recommendations in RA, describes measurement techniques to assess physical
      activity, and synthesizes the data from interventions to promote physical
      activity and improve health outcomes in adults with RA.

PMID- 23538739
TI  - Suspected acute exacerbation of idiopathic pulmonary fibrosis associated with
      interferon alpha therapy for hepatitis C: case report.
AB  - Interferon alpha (IFNalpha) has immune stimulatory actions implicated in its
      pulmonary toxicities. We describe deterioration of idiopathic pulmonary fibrosis
      (IPF) associated with IFNalpha treatment for chronic hepatitis C in a 58 year old
      woman culminating in a fatal suspected acute exacerbation of IPF (AE-IPF).
      Caution should be exercised in the use of IFNalpha in subjects with concomitant
      IPF given its known immunostimulatory effects and possible role in this suspected
      AE-IPF. 

PMID- 23538740
TI  - Applications of metabolomics for kidney disease research: from biomarkers to
      therapeutic targets.
AB  - Metabolomics is one of the relative newcomers of the omics techniques and is
      likely the one most closely related to actual real-time disease pathophysiology.
      Hence, it has the power to yield not only specific biomarkers but also insight
      into the pathophysiology of disease. Despite this power, metabolomics as applied
      to kidney disease is still in its early adolescence and has not yet reached the
      mature stage of clinical application, i.e., specific biomarker and therapeutic
      target discovery. On the other hand, the insight gained from hints into what
      makes these diseases tick, as is evident from the metabolomics pathways which
      have been found to be altered in kidney cancer, are now beginning to bear fruit
      in leading to potential therapeutic targets. It is quite likely that, with
      greater numbers of clinical materials and with more investigators jumping into
      the field, metabolomics may well change the course of kidney disease research. 

PMID- 23538741
TI  - Individualized hepatocellular carcinoma risk: the challenges for designing
      successful chemoprevention strategies.
AB  - Hepatocellular carcinoma (HCC) develops in the context of environmental risk
      factors like chronic viral hepatitis, diabetes and alcohol exposure, often
      associated to an increased risk of cirrhosis. Antiviral treatments that are
      effective to counteract hepatitis B and C may also attenuate the risk of tumor
      development. However, since hepatitis B-related carcinogenesis is promoted
      independently of the onset of cirrhosis, such antiviral treatments as
      nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical
      decompensation and variceal bleeding but not HCC. This means that in successfully
      treated patients with cirrhosis, HCC is often the consequence of their extended
      survival. In hepatitis C patients, a sustained virological response to interferon
      based therapies can reduce the rate of HCC development, even in patients with
      cirrhosis who experience histological regression of their liver disease. Future
      therapies aimed at this endpoint in at risk populations should take into
      consideration pretreatment patient stratification for host, viral and
      environmental risk factors. In this context the recent discovery of single
      nucleotide polymorphisms involved in the immune system function and
      tumorigenesis, might permit enrollment of populations of patients enriched with
      HCC risk factors for targeted chemopreventive therapies. This could finally pave
      the way to personalized algorithms, as already seen in the diagnosis and
      treatment schemes for chemoprevention.

PMID- 23538743
TI  - Relationship between interleukin-6 and cardiac involvement in systemic sclerosis.
AB  - OBJECTIVES: To explore the relationship between IL-6 levels and echocardiographic
      abnormalities, and N-terminal probrain natriuretic peptide (NT-proBNP) levels in
      SSc patients and to correlate tested parameters with European Scleroderma
      Activity (EUSTAR) score. METHODS: This case-control study included 31 SSc
      patients with preserved left ventricular ejection fraction (LVEF) and 32 matched
      healthy controls. Serum IL-6 and NT-proBNP levels were measured and subjects were
      evaluated by conventional and pulsed-wave tissue Doppler echocardiography.
      RESULTS: The level of IL-6 was significantly increased in patients with SSc (3.2
      vs 2.2 pg/ml, P < 0.001). SSc patients had significantly lower values of LV
      systolic (7.7 vs 9.25 cm/s, P < 0.001) and early diastolic (8.7 vs 10.3 cm/s, P =
      0.014) myocardial velocities and higher E/e' (9.04 vs 7.37, P = 0.001) ratio,
      although there was no between-group difference according to LVEF (68% vs 65%, P =
      0.248). On evaluating the right ventricle there was no significant between-group
      difference in systolic tricuspid annular velocity (13 vs 13.9 cm/s, P = 0.105),
      but the peak early diastolic velocity was significantly lower (11.7 vs 13.6, P =
      0.044) and E/e' was significantly higher (4.3 vs 3.38, P = 0.008) in SSc
      patients. IL-6 level showed correlation with LV mean e' (r = -0.57, P = 0.001),
      E/e' (r = 0.55, P = 0.001) and NT-proBNP (r = 0.52, P = 0.003). EUSTAR score
      correlated with LV E/e' (r = 0.48, P = 0.006), mean e' (r = -0.67, P < 0.001),
      mean s' (r = -0.51, P = 0.004), NT-proBNP (r = 0.60, P < 0.001) and IL-6 (r =
      0.79, P < 0.001). CONCLUSION: IL-6 level is increased in patients with SSc and
      significantly correlates with LV diastolic dysfunction, NT-proBNP and EUSTAR
      score. These results support the role of IL-6 in the development of cardiac
      disease in SSc patients.

PMID- 23538742
TI  - Inflammation and Gliomagenesis: Bi-Directional Communication at Early and Late
      Stages of Tumor Progression.
AB  - Inflammation has been closely linked to various forms of cancer. Less is known
      about the role of inflammation in glioma, especially at the initiation stage. In
      this review, we first describe the unique features of the immune system in the
      brain. We then discuss the current understanding of the mechanisms by which
      glioma cells modulate the immune system, especially how bi-directional
      communications between immune cells and glioma cells create an immunosuppressed
      microenvironment that promotes tumor survival and growth. We also address the
      potential tumor-initiating roles of inflammation in glioma. Finally, we describe
      several immunotherapy approaches currently being developed to reverse these
      interactions and stimulate the immune system to eliminate glioma cells.

PMID- 23538744
TI  - Shell shock: Psychogenic gait and other movement disorders-A film review.
AB  - BACKGROUND: The psychological pressure on soldiers during World War I (WWI) and
      other military conflicts has resulted in many reported cases of psychogenic gait
      as well as other movement disorders. In this paper, psychogenic movement
      disorders captured in the WWI film footage "War Neuroses" is reanalyzed. METHODS:
      Two movement disorders specialists re-examined film images of 21 WWI patients
      with various and presumed psychogenic manifestations, pre- and post treatment.
      The film was recorded by Arthur Hurst, a general physician with an interest in
      neurology. RESULTS: All 21 subjects were males, and all presented with symptoms
      relating to war trauma or a psychological stressor (e.g., being buried, shrapnel
      wounds, concussion, or trench fever). The most common presenting feature was a
      gait disorder, either pure or mixed with another movement disorder (15), followed
      by retrograde amnesia (2), abnormal postures (pure dystonia) (1), facial spasm
      (1), head tremor (1), "hyperthyroidism-hyperadrenalism" (1). Nineteen patients
      received treatment, and the treatment was identified in nine cases. In most
      cases, treatment was short and patients improved almost immediately. Occupational
      therapy was the most common treatment. Other effective methods were hypnosis (1),
      relaxation (1), passive movements (2), and probable "persuasion and re-education"
      (6). DISCUSSION: The high success rate in treating psychogenic disorders in
      Hurst's film would be considered impressive by modern standards, and has raised
      doubt in recent years as to whether parts of the film were staged and/or acted.

PMID- 23538745
TI  - Sleep-disordered breathing and postoperative outcomes after elective surgery:
      analysis of the nationwide inpatient sample.
AB  - BACKGROUND: Systematic screening and treatment of sleep-disordered breathing
      (SDB) or obstructive sleep apnea (OSA) in presurgical patients would impose a
      significant cost burden; therefore, it is important to understand whether SDB is
      associated with worse postoperative outcomes. We sought to determine the impact
      of SDB on postoperative outcomes in patients undergoing four specific categories
      of elective surgery (orthopedic, prostate, abdominal, and cardiovascular). The
      primary outcomes were in-hospital death, total charges, and length of stay (LOS).
      Two secondary outcomes of interest were respiratory and cardiac complications.
      METHODS: Data were obtained from the Nationwide Inpatient Sample database.
      Regression models were fitted to assess the independent association between SDB
      and the outcomes of interest. RESULTS: The cohort included 1,058,710 hospitalized
      adult patients undergoing elective surgeries between 2004 and 2008. SDB was
      independently associated with decreased mortality in the orthopedic (OR, 0.65;
      95% CI, 0.45-0.95; P = .03), abdominal (OR, 0.38; 95% CI, 0.22-0.65; P = .001),
      and cardiovascular surgery groups (OR, 0.54; 95% CI, 0.40-0.73; P < .001) but had
      no impact on mortality in the prostate surgery group. SDB was independently
      associated with a small, but statistically significant increase in estimated mean
      LOS by 0.14 days (P < .001) and estimated mean total charges by $860 (P < .001)
      in the orthopedic surgery group but was not associated with increased LOS or
      total charges in the prostate surgery group. In the abdominal and cardiovascular
      surgery groups, SDB was associated with a significant decrease in adjusted mean
      LOS of 1.1 days and 0.35 days, respectively (P < .001 for both groups), and
      adjusted mean total charges of $3,814 and $4,592, respectively (P < .001 for both
      groups). SDB was independently associated with a significantly increased OR for
      emergent intubation and mechanical ventilation, noninvasive ventilation, and
      atrial fibrillation in all four surgical categories. Emergent intubation occurred
      significantly earlier in the postoperative course in patients with SDB. In the
      subgroup of patients requiring emergent intubation, LOS, total charges,
      pneumonias, and in-hospital death were significantly higher in those without SDB.
      CONCLUSIONS: In this large national study, despite the increased independent
      association of SDB with postoperative cardiopulmonary complications, the
      diagnosis of SDB was not independently associated with an increased rate of in
      hospital death. SDB had a mixed impact on LOS and total charges by surgical
      category.

PMID- 23538746
TI  - Antivirally active ribavirin analogues--4,5-disubstituted 1,2,3-triazole
      nucleosides: biological evaluation against certain respiratory viruses and
      computational modelling.
AB  - BACKGROUND: Ribavirin is a broad-spectrum antiviral agent that derives some of
      its activity from inhibition of cellular inosine monophosphate dehydrogenase
      (IMPDH), resulting in lower guanosine triphosphate (GTP) levels. Here we report
      the biological activities of three ribavirin analogues. METHODS: Antiviral
      activities of test compounds were performed by in vitro cytopathic effect
      inhibition assays against influenza A (H1N1, H3N2 and H5N1), influenza B,
      measles, parainfluenza type 3 (PIV-3) and respiratory syncytial viruses.
      Compounds were modelled into the ribavirin 5'-monophosphate binding site of the
      crystallographic structure of the human type II IMPDH (hIMPDH2) ternary complex.
      Effects of compounds on intracellular GTP levels were performed by strong anion
      exchange HPLC analysis. RESULTS: Of the three compounds evaluated, the 5-ethynyl
      nucleoside (ETCAR) exhibited virus-inhibitory activities (at 1.2-20 MUM,
      depending upon the virus) against most of the viruses, except for weak activity
      against PIV-3 (62 MUM). Antiviral activity of ETCAR was similar to ribavirin;
      however, cytotoxicity of ETCAR was greater than ribavirin. Replacing the 5
      ethynyl group with a 5-propynyl or bromo substituent (BrCAR) considerably reduced
      antiviral activity. Computational studies of ternary complexes of hIMPDH2 enzyme
      with 5'-monophosphates of the compounds helped rationalize the observed
      differences in biological activity. All compounds suppressed GTP levels in cells;
      additionally, BrCAR suppressed adenosine triphosphate and elevated uridine
      triphosphate levels. CONCLUSIONS: Three compounds related to ribavirin inhibited
      IMPDH and had weak to moderate antiviral activity. Cytotoxicity adversely
      affected the antiviral selectivity of ETCAR. As with ribavirin, reduction in
      intracellular GTP may play a role in virus inhibition.

PMID- 23538747
TI  - Correlation of the rates of solvolysis of tert-butyl chlorothioformate and
      observations concerning the reaction mechanism.
AB  - The "parent" tertiary alkyl chloroformate, tert-butyl chloroformate, is unstable,
      but the tert-butyl chlorothioformate (1) is of increased stability and a kinetic
      investigation of the solvolyses is presented. Analyses in terms of the simple and
      extended Grunwald-Winstein equations are carried out. The original one-term
      equation satisfactorily correlates the data with a sensitivity towards changes in
      solvent ionizing power of 0.73 +/-0.03. When the two-term equation is applied,
      the sensitivity towards changes in solvent nucleophilicity of 0.13 +/- 0.09 is
      associated with a high (0.17) probability that the term that it governs is not
      statistically significant.

PMID- 23538748
TI  - Development of an in situ culture-free screening test for the rapid detection of
      Staphylococcus aureus within healthcare environments.
AB  - This article reports the development of a novel fluorometric indicator which
      shows a rapid response when exposed to coagulase positive Staphylococcus aureus
      (SA) bacteria (including methicillin sensitive Staphylococcus aureus (MSSA) and
      methicillin resistant Staphylococcus aureus (MRSA) bacteria). The test is robust
      and will detect a wide variety of SA strains and there is no significant
      fluorescence response observed for other species of bacteria commonly found in
      clinical specimens, including other Staphylococcus bacteria. This research forms
      the basis of a prototype SA testing kit for the rapid detection of SA within
      hospital and healthcare environments as an economical prescreen or alternative to
      the current PCR based testing methodology. Rapid identification of SA carriers
      will allow hospital infection control teams to be pre-emptive and could
      significantly reduce the incidence of hospital acquired infections involving this
      organism.

PMID- 23538749
TI  - Impact of IKZF1 deletions and PAX5 amplifications in pediatric B-cell precursor
      ALL treated according to NOPHO protocols.

PMID- 23538750
TI  - Disruption of the MYC-miRNA-EZH2 loop to suppress aggressive B-cell lymphoma
      survival and clonogenicity.
AB  - c-MYC (hereafter MYC) overexpression has been recognized in aggressive B-cell
      lymphomas and linked to adverse prognosis. MYC activation results in widespread
      repression of micro-RNA (miRNA) expression and associated with lymphoma
      aggressive progression. Our recent study identified a MYC-miRNA-EZH2 feed-forward
      loop linking overexpression of MYC, EZH2 and miRNA repression. Here, using a
      novel small-molecule BET bromodomain inhibitor, JQ1, and the EZH2 inhibitor,
      DZNep, we demonstrated that combined treatment of JQ1 and DZNep cooperatively
      disrupted MYC activation, resulting in a greater restoration of miR-26a
      expression and synergistically suppressed lymphoma growth and clonogenicity in
      aggressive lymphoma cells. Furthermore, CHIP assay demonstrated that MYC
      recruited EZH2 to miR-26a promoter and cooperatively repressed miR-26a expression
      in aggressive lymphoma cell lines, as well as primary lymphoma cells. Loss- or
      gain-of-function approaches revealed that miR-26a functioned as a tumor
      suppressor miRNA and mediated the combinatorial effects of JQ1 and DZNep. These
      findings represent a novel promising approach for silencing MYC-miRNA-EZH2
      amplification loop for combinatorial therapy of aggressive B-cell lymphomas. 

PMID- 23538751
TI  - Global H3K4me3 genome mapping reveals alterations of innate immunity signaling
      and overexpression of JMJD3 in human myelodysplastic syndrome CD34+ cells.
AB  - The molecular bases of myelodysplastic syndromes (MDS) are not fully understood.
      Trimethylated histone 3 lysine 4 (H3K4me3) is present in promoters of actively
      transcribed genes and has been shown to be involved in hematopoietic
      differentiation. We performed a genome-wide H3K4me3 CHIP-Seq (chromatin
      immunoprecipitation coupled with whole genome sequencing) analysis of primary MDS
      bone marrow (BM) CD34+ cells. This resulted in the identification of 36 genes
      marked by distinct higher levels of promoter H3K4me3 in MDS. A majority of these
      genes are involved in nuclear factor (NF)-kappaB activation and innate immunity
      signaling. We then analyzed expression of histone demethylases and observed
      significant overexpression of the JmjC-domain histone demethylase JMJD3 (KDM6b)
      in MDS CD34+ cells. Furthermore, we demonstrate that JMJD3 has a positive effect
      on transcription of multiple CHIP-Seq identified genes involved in NF-kappaB
      activation. Inhibition of JMJD3 using shRNA in primary BM MDS CD34+ cells
      resulted in an increased number of erythroid colonies in samples isolated from
      patients with lower-risk MDS. Taken together, these data indicate the
      deregulation of H3K4me3 and associated abnormal activation of innate immunity
      signals have a role in the pathogenesis of MDS and that targeting these signals
      may have potential therapeutic value in MDS.

PMID- 23538752
TI  - mTOR regulates DNA damage response through NF-kappaB-mediated FANCD2 pathway in
      hematopoietic cells.
AB  - Hematopoietic stem/progenitor cells (HSPCs) function to give rise to mature blood
      cells. Effective DNA damage response (DDR) and maintenance of genomic stability
      are crucial for normal functioning of HSPCs. Mammalian target of rapamycin (mTOR)
      integrates signals from nutrients and growth factors to control protein
      synthesis, cell growth, survival and metabolism, and has been shown to regulate
      DDR in yeast and human cancer cells through the p53/p21 signaling cascade. Here,
      we show that gene targeting of mTOR in HSPCs causes a defective DDR due to a
      variety of DNA damage agents, mimicking that caused by deficient FANCD2, a key
      component of the Fanconi anemia (FA) DDR machinery. Mechanistically, mTOR(-/-)
      HSPCs express drastically reduced FANCD2. Consistent with these genetic findings,
      inactivation of mTOR in human lymphoblast cells by pp242 or Torin 1, mTOR kinase
      inhibitors, suppresses FANCD2 expression and causes a defective DDR that can be
      rescued by reconstitution of exogenous FANCD2. Further mechanistic studies show
      that mTOR deficiency or inactivation increases phosphorylation and nuclear
      translocation of nuclear factor (NF)-kappaB, which results in an enhanced NF
      kappaB binding to FANCD2 promoter to suppress FANCD2 expression. Thus, mTOR
      regulates DDR and genomic stability in hematopoietic cells through a noncanonical
      pathway involving NF-kappaB-mediated FANCD2 expression. 

PMID- 23538754
TI  - Bonding performance of a newly developed step-less all-in-one system on dentin.
AB  - The purpose of this study was to evaluate the short-term uTBS (Micro-tensile bond
      strength) and microscopic (SEM and TEM) observation of four recent adhesives. One
      adhesive was an experimental step-less 1-step system (LLB-2, Tokuyama Dental),
      which is an all-in-one system without the light-curing step in the application
      process. The other two were self-adhering light-cured flowable composite resin
      systems FLD (Fusio Liquid Dentin, Pentron Clinical Technologies) and VF (Vertise
      Flow Dental Restorative Materials, Kerr Corporation), which combine all the
      bonding steps together. A 2-step self-etching system MG (Clearfil MegaBond,
      Kuarary Medical) was employed as the control group in this study. The uTBS of MG
      was the highest (79.0 MPa) followed by that of LLB-2 (63.1 MPa), FLD (23.6 MPa),
      and VF (13.1 MPa). The microscopic observations showed that MG and LLB-2 had an
      approximately 20 um and 5 um adhesive layer respectively, without bubble or gap
      formation at the resin-dentin interface, which were found in FLD and VF.

PMID- 23538753
TI  - Adipose-derived stromal/stem cells: a primer.
AB  - Until recently, the complexity of adipose tissue and its physiological role was
      not well appreciated. This changed with the discovery of adipokines such as
      leptin. The cellular composition of adipose tissue is heterogeneous and changes
      as a function of diabetes and disease states such as diabetes. Tissue engineers
      view adipose tissue as a rich source of adult stromal/stem cells isolated by
      collagenase digestion. In vitro and in vivo studies have documented that adipose
      stromal/stem cells are multipotent, with the ability to differentiate along the
      adipocyte, chondrocyte, osteoblast and other lineage pathways. The adipose
      stromal/stem cells secrete a wide range of cytokines and growth factors with
      potential paracrine actions. Furthermore, adipose stromal/stem cells exert
      immunomodulatory functions when added to mixed lymphocyte reactions, suggesting
      that they can be transplanted allogeneically. This review article focuses on
      these mechanisms of adipose stromal/stem cell action and their potential utility
      as cellular therapeutics. 

PMID- 23538755
TI  - Development and evaluation of a low-erosive apple juice drink with Phosphoryl
      Oligosaccharides of Calcium.
AB  - This study aimed to evaluate effectiveness of Phosphoryl-Oligosaccharides of
      Calcium (POs-Ca) added to apple juice on enamel erosion. Five juices were
      prepared by adding 0%, 0.5%, 1%, 1.5% or 2% POs-Ca to commercial apple juice, and
      subjected to Visual Analogue Scale (VAS) taste evaluation and pH and
      calcium/inorganic-phosphates analyses. To evaluate erosion, polished bovine
      enamel blocks were immersed in each juice for 5 or 60 min (n=20). Enamel surface
      loss (SL) and roughness (Ra) were also analyzed. VAS indicated acceptable taste
      for juices containing up to 1% POs-Ca. POs-Ca addition resulted in increased pH
      (3.61-3.88), calcium (0.95-25.10 mM), and inorganic-phosphate (1.77-20.44 mM).
      After 5 min, 0% juice resulted in significant erosion (p<0.05). However even
      after 60 min, no significant increase was found in Ra and SL compared to water
      (control) for 1.5-2% juices (p>0.05). Addition of 1-1.5% POs-Ca could
      significantly reduce enamel erosion by apple juice maintaining an acceptable
      taste.

PMID- 23538756
TI  - Effects of sandblasting, H2SO4/HCl etching, and phosphate primer application on
      bond strength of veneering resin composite to commercially pure titanium grade 4.
AB  - This study investigated the effects of surface treatments on the bond strength of
      a resin composite to a commercially pure titanium. The bonding surfaces of all
      titanium specimens were ground with 1,000-grit silicon carbide paper and then
      subjected to one or more of these surface treatments: sandblasting with alumina
      (sand), etching with 45wt% H2SO4 and 15wt% HCl (SH-etchant) at 70 degrees C for
      10 min, and/or phosphate primer (MDP-primer) application. Specimens not subjected
      to any surface treatment were used as controls. After resin composite veneer
      placement and 24-h water immersion, the shear bond strengths of the specimens in
      descending order were: sand/SH-etchant/MDP-primer, sand/SH-etchant/no primer, no
      sand/SH-etchant/MDP-primer, sand/no etch/MDP-primer, no sand/SH-etchant/no
      primer, sand/no etch/no primer, no sand/no etch/MDP-primer, no sand/no etch/no
      primer. Scanning electron microscope observations revealed that sandblasting and
      SH-etchant created many micro- and nanoscale cavities on the titanium surface.
      Results showed that a combined use of sandblasting, SH-etchant, and MDP-primer
      application had a cooperative effect on titanium bonding.

PMID- 23538757
TI  - Flexural properties of resin composites: influence of specimen dimensions and
      storage conditions.
AB  - This study evaluated the influence of specimen dimensions and storage medium and
      temperature on the flexural properties of one dental resin composite. The
      material utilized throughout the study was Clearfil AP-X. Eighty specimens were
      built with dimensions of either 10*2*2 mm or 25*2*2 mm, stored dry or in
      distilled water, at 25 or 37oC, for 24 h. Flexural strength and modulus were
      tested in three-point bending. Results were evaluated with three-way ANOVA and
      Tukey's test (alpha=0.05). Statistical significance was observed for all three
      factors: temperature (37oC=190.8 MPa, 25oC=165.3 MPa; p<0.01), storage medium
      (water=167.7 MPa, Dry=188.4 MPa; p<0.01) and specimen dimensions (10*2*2 mm=197.9
      MPa, 25*2*2 mm=158.2 MPa; p<0.01). None of the interactions were significant.
      Within the limitations of this study, it can be concluded that factors such as
      specimen dimensions, storage medium and temperature significantly affect flexural
      strength results, which invalidates comparisons of results from studies that use
      different methodologies.

PMID- 23538758
TI  - Early gene and protein expression associated with osteoblast differentiation in
      response to fish collagen peptides powder.
AB  - This study was designed to investigate the biological effects of fish collagen
      peptide (FCP) on human osteoblasts. Human osteoblasts were treated with 0.1% FCP,
      which was the optimal concentration confirmed by the increase in alkaline
      phosphatase activity. After one, three, five and seven days of culture, the
      number of FCP-treated cells increased significantly compared with untreated
      cells. In a real-time PCR analysis, the expression of osteocalcin, osteopontin,
      BMP-2 and integrin beta3 mRNAs in FCP-treated cells showed increases compared
      with untreated cells after three days of culture. After seven days of culture,
      the expression levels of osteopontin and integrin beta3 were still higher in the
      FCP-treated cells than in untreated cells. The production of osteocalcin,
      osteopontin and integrin beta3 proteins in FCP-treated cells also showed
      increases after seven days of culture. Furthermore, FCP accelerated matrix
      mineralization in the cultures. The present study indicates the potential utility
      of FCP as a biomaterial.

PMID- 23538759
TI  - Cariotester, a new device for assessment of dentin lesion remineralization in
      vitro.
AB  - This study aimed to evaluate the potential of a new device (Cariotester) for
      monitoring of incipient carious lesion remineralization in root dentin by topical
      fluoride in vitro. Demineralized bovine dentin specimens were treated by fluoride
      solutions (APF or neutral NaF) and remineralized for 4 weeks. Cariotester was
      used to measure penetration depth (CTR depth) of the indenter into the de- and
      remineralized specimen surface. The specimens were assessed by transverse
      microradiography (TMR) to determine lesion parameters (depth: LD, mineral loss:
      DeltaZ). Pearson's correlation analysis showed an overall significant
      relationship between CTR depth and both TMR parameters. CTR depth appeared to
      distinguish the positive effect that topical fluoride application had on the
      remineralization of the outer zone of dentin lesions. Cariotester had the
      potential to serve as a quantitative tool for monitoring of incipient carious
      lesion remineralization in root dentin.

PMID- 23538760
TI  - Pre-treatment of radicular dentin by self-etch primer containing chlorhexidine
      can improve fiber post bond durability.
AB  - We evaluated whether the pre-treatment of radicular dentin by ED Primer
      containing different concentrations of chlorhexidine can improve the bond
      durability of fiber post to radicular dentin. Experimental ED primers containing
      different concentrations of chlorhexidine (0%, 0.5% and 1.0%) were prepared.
      Thirty extracted maxillary anterior teeth were divided into 3 groups, each group
      corresponding to different chlorhexidine concentrations. Fiber posts were
      cemented in endodontically treated teeth with experimental ED primers and Panavia
      F. The bonded teeth were transversally sectioned into six slices and then were
      processed for thin slice push-out test 24 h later or after 18-months water
      storage. Eighteen-month storage resulted in significant bond strength reduction
      of all groups (p<0.05). The bond strength reduction of 1.0% group was
      significantly lower than that of control group and 0.5% group (p<0.05). In
      conclusion, the incorporation of 1.0% chlorhexidine into ED primer can extend the
      bond longevity of fiber post to radicular dentin.

PMID- 23538761
TI  - Periodontal regeneration following application of basic fibroblast growth factor
      2 in combination with beta tricalcium phosphate in class III furcation defects in
      dogs.
AB  - The aim of this study was to investigate the effect of tunnel structured beta
      tricalcium phosphate (beta-TCP) on the regenerative potential of basic fibroblast
      growth factor-2 (bFGF-2) in class III furcation defects in dogs. The furcations
      of 30 mandibular premolar teeth received: 1) 0.3% bFGF-2 solution in conjunction
      with beta-TCP; 2) 0.3% bFGF-2 solution; and 3) no implant material (Control
      group). The dogs were sacrificed 8 weeks post-surgery, and healing was evaluated
      histologically. New bone formation was significantly greater in the bFGF-2/beta
      TCP group compared to the bFGF-2 solution and Control groups (p<0.01). New
      cementum formation in the bFGF-2/beta-TCP and bFGF-2 solution groups was
      significantly greater than that in the Control group (p<0.01). These findings
      suggested that bFGF-2 alone enhances connective tissue attachment in a manner
      similar to the combination of bFGF-2 and beta-TCP. Furthermore, this combination
      enhances bone formation up to the fornix in class III furcation defects.

PMID- 23538762
TI  - Compatibility between silorane adhesive and simplified methacrylate-based
      adhesive systems.
AB  - The purpose of this study was to evaluate the impact of replacing P90 primer with
      simplified adhesive systems (with a conventional, two-step adhesive or a self
      etching, one-step adhesive) on bond strength to dentin in Class I restorations.
      The interfaces were also analyzed using confocal microscopy by adding a
      fluorophore to the adhesive components and SEM using silver nitrate for
      nanoleakage investigation. X-ray diffraction (XRD) characterized the chemical
      interaction of the adhesives. Failure mode and nanoleakage varied among groups.
      Characteristic micromorphology and higher nanoleakage were noted for silorane
      combinations. On the other hand, no signs of phase crystallization in the
      silorane adhesive combinations were noted. Replacing the silorane primer with
      simplified adhesives proved successful as the modified systems provided bonding
      to dentin comparable to that of the unmodified silorane systems. However, the
      dedicated adhesive exhibited signs of degradation immediately after application,
      which may impact the longevity of restorations in short periods.

PMID- 23538763
TI  - Influence of surface treatment of yttria-stabilized tetragonal zirconia
      polycrystal with hot isostatic pressing on cyclic fatigue strength.
AB  - Hot isostatic pressing processed yttria-stabilized tetragonal zirconia
      polycrystal (HIP Y-TZP) has the potential for application to implants due to its
      high mechanical performance. The aim of this study was to investigate the
      influence of surface treatment of HIP Y-TZP on cyclic fatigue strength. HIP Y-TZP
      specimens were subjected to different surface treatments. Biaxial flexural
      strength was determined by both static and cyclic fatigue testing. In the cyclic
      fatigue test, the load was applied at a frequency of 10 Hz for 10(6) cycles in
      distilled water at 37 degrees C. The surface morphology, roughness, and crystal
      phase of the surfaces were also evaluated. The cyclic fatigue strength (888 MPa)
      of HIP Y-TZP with sandblasting and acid-etching was more than twice that of Y-TZP
      as specified in ISO 13356 for surgical implants (320 MPa), indicating the
      clinical potential of this material.

PMID- 23538764
TI  - Calcium phosphates deposited on titanium electrode surface--part 1: Effect of the
      electrode polarity and oxide film on the deposited materials.
AB  - We report experimental results about the effect of polarity of electrode and
      anodized titanium oxide film on the deposited materials by electrolysis of an
      acidic calcium phosphate solution. Mirror-polished titanium and anodized titanium
      were used as anode or cathode, and a Pt plate was used as a counter electrode.
      The load voltage was held constant at 20 VDC. No deposited materials were found
      on the anode surface. On the other hand, dicalcium phosphate dihydrate (DCPD) was
      deposited on the cathode surface at the beginning of the electrolysis. After the
      electrolysis time 600 s, the non-stoichiometric hydroxyapatite (HAp) with several
      hundred nanometers was formed on the specimen surface. Based on X-ray
      photoelectron spectroscopy data, the anodized oxide film contained both P(5+) and
      P(3+) ions. This characteristic of the oxide film and the electrolysis conditions
      were related to the behavior of the deposition of ultra fine HAp with high
      crystallinity.

PMID- 23538765
TI  - Effect of framework design on the surface strain of zirconia fixed partial
      dentures.
AB  - The purpose of this study was to evaluate the design of resin-bonded fixed
      partial dentures (RBFPDs) with zirconia frameworks. The abutment teeth were the
      upper central incisor and the canine. Three types of frameworks were fabricated
      as follows: 0.5-mm- and 0.8-mm-thick zirconia frameworks with grooves and holes
      (0.5ZrG, 0.8ZrG) and 0.5-mm-thick zirconia frameworks without grooves and holes
      (0.5Zr). The control group was designed as a 0.8-mm-thick metal framework with
      grooves and holes (0.8MG). Static loading was applied and the surface strain of
      the retainers was measured with strain gages. The magnitude of the principal
      strain of the 0.5ZrG framework was significantly lower than that of the 0.8MG and
      the 0.5Zr frameworks. This result suggests that the zirconia and retention form
      had a significant effect on decreasing the framework deformation, indicating that
      the RBFPDs that use a 0.5-mm thick zirconia framework are effective for replacing
      a single anterior missing tooth.

PMID- 23538766
TI  - Fluoride release and recharge abilities of contemporary fluoride-containing
      restorative materials and dental adhesives.
AB  - The aim of this study was to evaluate the fluoride release of five fluoride
      releasing restorative materials and three dental adhesives, before and after NaF
      solution treatment. Five restorative materials (Fuji IX GP, GC Corp.; Ketac N100,
      3M ESPE; Dyract Extra, Dentsply; Beautifil II, Shofu Inc.; Wave, SDI) and three
      dental adhesives (Stae, SDI; Fluorobond II - Shofu Inc.; Prime & Bond NT,
      Dentsply) were investigated before and after NaF solution treatment. A fluoride
      ion-selective electrode was to measure fluoride concentrations. During the 86-day
      period before NaF solution treatment, Fuji IX GP released the highest amount of
      fluoride among the restorative materials while Prime & Bond NT was the highest
      among the dental adhesives. After NaF solution treatment, Fuji IX GP again ranked
      the highest in fluoride release among the restorative materials while Fluorobond
      II ranked the highest among dental adhesives. It was concluded that the
      compositions and setting mechanisms of fluoride-containing dental materials
      influenced their fluoride release and recharge abilities.

PMID- 23538767
TI  - Influence of electrolytic treatment time on the corrosion resistance of Ni-Ti
      orthodontic wire.
AB  - The purpose of this study was to examine the use of electrolytic treatment, which
      can improve the corrosion resistance of Ni-Ti orthodontic wires, to minimize
      adverse effects. Electrolytic treatment of Ni-Ti wires was performed in a
      solution composed of glycerol and lactic acid for 5, 15, or 30 min. The anodic
      polarization test, three-point bending test, and X-ray photoelectron
      spectroscopic analysis of the wire surface were performed to explore an optimal
      treatment condition. Breakdown potentials of treated wires increased with
      increasing treatment time and higher corrosion resistance was obtained by
      performing the electrolytic treatment for more than 5 min. The relative
      concentration of nickel in the layer was decreased in inverse proportion to the
      treatment time. The results suggest that the commercial Ni-Ti wire with low
      corrosion resistance can be improved by the electrolytic treatment for more than
      5 min.

PMID- 23538768
TI  - Preparation of an orthodontic bracket coated with an nitrogen-doped TiO(2-x)N(y)
      thin film and examination of its antimicrobial performance.
AB  - A bracket coated with a nitrogen-doped (N-doped) TiO(2-x)N(y) thin film was
      prepared using the RF magnetron sputtering method. The physicochemical properties
      of the thin film were measured using X-ray diffraction and energy-dispersive X
      ray spectrometry, while the antimicrobial activity of the bracket against common
      oral pathogenic microbes was assessed on the basis of colony counts. The rate of
      antimicrobial activity of the bracket coated with nano-TiO(2-x)N(y) thin film
      against Streptococcus mutans, Lactobacillus acidophilus, Actinomyces viscous, and
      Candida albicans was 95.19%, 91.00%, 69.44%, and 98.86%, respectively. Scanning
      electron microscopy showed that fewer microbes adhered to the surface of this
      newly designed bracket than to the surface of the normal edgewise bracket. The
      brackets coated with the N-doped TiO(2-x)N(y) thin film showed high antimicrobial
      and bacterial adhesive properties against normal oral pathogenic bacterial
      through visible light, which is effective in prevention of enamel
      demineralization and gingivitis in orthodontic patients.

PMID- 23538769
TI  - New development of carbonate apatite-chitosan scaffold based on lyophilization
      technique for bone tissue engineering.
AB  - Carbonate apatite-chitosan scaffolds (CA-ChSs) were fabricated using the
      lyophilization technique. It was found that ChSs prepared with 200 mg chitosan
      powder (ChSs200) had well-structured three-dimensional architecture with high
      porosity and good retentive form without brittleness. In addition, it was shown
      that the number of osteoblast-like cells MC3T3-E1 proliferated on desalinated
      ChSs200 was larger than that on the non-desalinated ChSs200. CA-ChSs were
      fabricated by adding 100 mg carbonate apatite (CA) to 200 mg chitosan gels
      followed by freeze-drying (CA100ChSs200). SEM observation revealed that
      CA100ChSs200 had favorable three- dimensional porous structures. The number of
      living cells increased more rapidly on CA100ChSs200 prepared with different
      amounts of CA than on ChSs. ALP activity significantly increased after day 14 and
      reached a plateau after day 21 in ChSs200 and CA100ChSs200. It was concluded that
      newly developed CA100ChSs200 may be a possible scaffold material for tissue
      engineering.

PMID- 23538770
TI  - Effect of different beverages on the color stability and degree of conversion of
      nano and microhybrid composites.
AB  - This study sought to evaluate the effects of different staining solutions on the
      colour stability of nanocomposites compared with microhybrid resin and to
      evaluate the degree of conversion of these two materials. Two different shades of
      two different composites were cured in polytetraflouroethylene disk rings.
      Coffee, tea and cola drinks were used as staining solutions, and distilled water
      was used as a control. Data were statistically analysed using a paired T-test
      with a significance level of 5%. Nano composite showed the highest degree of
      conversion (DC) values based on calculation of the bonded and free carbonyl peak
      intensities in the spectrum. The colour analysis showed that nanohybrid had the
      highest DeltaE values when exposed to coffee solutions; they showed less color
      stability despite having a higher degree of conversion. Nano resin composite
      showed significantly higher discoloration than microhybrid composite.

PMID- 23538771
TI  - Comparison of denture base resin reinforced with polyaromatic polyamide fibers of
      different orientations.
AB  - The aim of this study was to evaluate the effect of reinforcing polyaromatic
      polyamide (aramid) fibers with various orientations on the flexural properties of
      denture base resin. Aramid fibers with four orientations of unidirectional,
      woven, non-woven and paper-type were pre-impregnated and placed at the bottom of
      a specimen mold. Heat-polymerized denture base resin was packed over the fibers
      and polymerized. A three-point bending test was performed using a universal
      testing machine at a crosshead speed of 5 mm/min. The flexural strengths and
      flexural moduli of the unidirectional and woven groups were significantly higher
      than those of the control and other experimental groups.For the flexural moduli,
      all experimental groups showed significantly higher reinforcing effects than the
      control group. In conclusion, the unidirectional group located perpendicular to
      the direction of the load was most effective in reinforcing the denture base
      resin, followed by the woven group.

PMID- 23538772
TI  - Effect of adherend temperature on bond strengths of resin bonding systems to
      denture base resin and a semi-precious alloy.
AB  - This study investigated the effect of adherend temperature on shear bond
      strengths of auto-polymerizing resin to denture base resin and 4-META/MMA-TBBO
      resin to silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy. Bonding procedure was
      carried out when adherend temperature was 10, 23, 37, or 55 degrees C, and shear
      bond strengths (SBSs) were measured before and after thermocycling. Before
      thermocycling, there were no significant differences in bond strength among the
      four adherend temperatures for each adhesive resin: 31.59+/-6.11-32.89+/-2.12 MPa
      for auto-polymerizing resin; 35.43+/-2.2-38.38+/-0.61 MPa for 4-META/MMA-TBBO
      resin. After thermocycling, optimal adherend temperature to achieve the highest
      bond strength was 37 degrees C for auto-polymerizing resin to denture base resin
      (30.02+/-2.29 MPa) and 10oC for 4-META/MMA-TBBO resin to Ag-Pd-Cu-Au alloy
      (37.14+/-2.17 MPa).

PMID- 23538774
TI  - Congenital partial absence of the pericardium in a young man with atypical chest
      pain.
AB  - Pericardial defects are infrequent congenital anomalies due to agenesis caused by
      premature atrophy of the common cardinal vein or Cuvier duct during the 5(th) or
      6(th) week of embryonic life. These congenital defects are rare, typically
      observed as an incidental finding and usually remain asymptomatic. Nevertheless,
      the more widespread use of modern imaging techniques has contributed to an
      increase of its incidence in recent years. There is currently no consensus
      regarding therapeutic options, all of which are based on small retrospective
      studies that evaluate the risk of developing a life-threatening complication such
      as herniation and incarceration of the myocardium. We report on a 22-year-old
      male who presented with sudden onset of sharp chest pain and dyspnea. Computed
      tomography and cardiac magnetic resonance scan revealed a pericardial defect
      adjacent to the lateral free wall of the left atrium with associated herniation
      of the left atrial appendage. The patient was managed conservatively and had an
      uneventful clinical progress.

PMID- 23538773
TI  - Rates and impact of hepatitis on human immunodeficiency virus infection in a
      large African cohort.
AB  - AIM: To determine the rates and impact of hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infections on response to long-term highly active antiretroviral
      therapy (HAART) in a large human immunodeficiency virus (HIV) population in
      Nigeria. METHODS: HBV and HCV as well as HIV infections are endemic in sub
      Saharan Africa. This was a retrospective cohort study of 19,408 adults who were
      recruited between June 2004 and December 2010 in the AIDS Prevention Initiative
      in Nigeria in Nigeria programme at Jos University Teaching Hospital. Serological
      assays, including HBV surface antigen (HBsAg) and hepatitis C antibody were used
      to categorise hepatitis status of the patients. HBsAg was determined using enzyme
      immunoassay (EIA) (Monolisa HBsAg Ultra3; Bio-Rad). HCV antibody was tested using
      third generation EIA (DIA.PRO Diagnostic, Bioprobes srl, Milan, Italy). HIV RNA
      levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5
      (Roche Diagnostics, GmbH, Mannheim, Germany) with a detection limit of 400
      copies/mL. Flow cytometry was used to determine CD4+ cell count (Partec, GmbH
      Munster, Germany). Comparison of categorical and continuous variables were
      achieved using Pearson's chi(2) and Kruskal Wallis tests respectively, on MedCalc
      for Windows, version 9.5.0.0 (MedCalc Software, Mariakerke, Belgium). RESULTS:
      With an overall hepatitis screening rate of over 90% for each virus; HBV, HCV and
      HBV/HCV were detected in 3162 (17.8%), 1983 (11.3%) and 453 (2.5%) HIV infected
      adults respectively. The rate of liver disease was low, but highest among HIV
      mono-infected patients (29, 0.11%), followed by HBV co-infected patients (15,
      0.08%). Patients with HBV co-infection and triple infection had higher log10 HIV
      RNA loads (HBV: 4.6 copies/mL vs HIV only: 4.5 copies/mL, P < 0.0001) and more
      severe immune suppression (HBV: 645, 55.4%; HBV/HCV: 97, 56.7%) prior to
      initiation of HAART compared to HIV mono-infected patients (1852, 48.6%) (P <
      0.0001). Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts
      results at baseline and end of follow up were available for analyses, CD4
      increase was significantly lower in those with HBV co-infection (HBV: 144
      cells/mm(3); HBV/HCV: 105 cells/mm(3)) than in those with HCV co-infection (165
      cells/mm(3)) and HIV mono-infection (150 cells/mm(3)) (P = 0.0008). CONCLUSION:
      High rates of HBV and HCV infections were found in this HIV cohort. CD4 recovery
      was significantly diminished in patients with HBV co-infection.

PMID- 23538775
TI  - Bone metabolism compensates for the delayed growth in small for gestational age
      neonates.
AB  - The goal of the present study is to investigate the relationship between
      anthropometric and bone metabolism markers in a sample of neonates and their
      mothers. A sample of 20 SGA (small for the gestational age), AGA (appropriate for
      the gestational age) and LGA (large for the gestational age) term neonates and
      their 20 mothers was analyzed at birth and at exit. Elisa method was used to
      measure the OPG (Osteoprotegerin), RANK (Receptor activator of nuclear factor
      kappaB), RANKL (Receptor activator of nuclear factor-kappaB Ligand), IGF-1
      (Insulin-like growth factor 1), IGFBP3 (Insulin-like Growth Factor Binding
      Protein 3) and Leptin levels. Birth weight and length were positively correlated
      with RANKL, IGF-1 and IGFBP3 and negatively with the ratio OPG/RANKL. SGA
      neonates presented lower RANKL values and higher OPG/RANKL ratio while LGA
      neonates had higher RANK levels than AGA neonates. Positive association was shown
      between neonatal IGFBP3 and maternal IGF-1 values and between neonatal and
      maternal RANK values at birth and at exit. These results reveal a remarkable
      upregulation of OPG/RANKL ratio in SGA neonates, pointing out the role of bone
      turnover in compensating for the delayed neonatal growth.

PMID- 23538776
TI  - The optimization of a scaffold for cartilage regeneration.
AB  - Natural polymers offer various advantages in cartilage tissue engineering
      applications, thanks to their intrinsic bioactivity and adaptability, which can
      be exploited for the optimization of scaffold properties. In particular, silk
      fibroin has multifunctional features driven by the self-assembly of molecular
      subunits in appropriate environmental conditions. For these reasons, it was used
      in combination with hyaluronic acid to produce porous sponges for cartilage
      regeneration. The added amount of hyaluronic acid and the cross-linking with
      genipin modulated scaffold properties in a synergistic way, showing a strong
      inter-correlation among macroscopic and microscopic characteristics.
      Interestingly, hyaluronic acid affected silk fibroin conformation and induced a
      physical separation between the two material components in absence of genipin.
      Instead, this was prevented by the cross-linking reaction, resulting in a more
      interspersed network of protein and polysaccharide molecules partially resembling
      the structure of cartilage extracellular matrix. In addition, the systematic
      evaluation of sponge properties and how they can be modulated will represent a
      significant starting point for the interpretation of the complex outcomes driven
      by the scaffold in vitro and in vivo. 

PMID- 23538777
TI  - Non-viral gene-activated matrices: next generation constructs for bone repair.
AB  - In the context of producing enhanced therapeutics for regenerative medicine, our
      laboratory develops gene-activated matrices (GAMs) using non-viral gene therapy
      (GT) in combination with collagen-based scaffolds engineered specifically for
      tissue repair. Non-viral vectors have been referred to as a minority pursuit in
      GT but considering the concerns associated with viral vectors and as transient
      gene expression is such a key consideration, further research is clearly
      warranted for tissue engineering (TE) applications. Mesenchymal stem cells (MSCs)
      are well regarded for their capability in bone regeneration but as primary cells,
      they are difficult to transfect. We have recently optimised the non-viral vector,
      polyethyleneimine (PEI), to achieve high transfection efficiencies in MSCs.
      Subsequently, a series of PEI-based GAMs were developed using collagen, collagen
      glycosaminoglycan and collagen-nanohydroxyapatite (collagen-nHa) scaffolds
      whereby transgene expression was detected up to 21 d with the collagen-nHa
      scaffold providing the most prolonged expression. Moreover, all PEI-based GAMs
      contained a low plasmid DNA dose of 2 ug which is far below doses often required
      in previous GAMs. Having successfully developed these GAMs, the ephrinB2 gene has
      recently been incorporated to produce a novel therapeutic GAM for bone repair.
      Herein, we discuss our recent investigations in the development and application
      of non-viral GAMs.

PMID- 23538778
TI  - Bone marrow endothelial progenitors in atherosclerotic plaque resolution.
AB  - Atherosclerosis is a major cause of morbidity and mortality in the United States.
      Persistently elevated circulating low-density lipoprotein, or
      hypercholesterolemia, and deposition of low-density lipoprotein in the vascular
      wall are the main inducers of atherosclerosis, which manifests itself as arterial
      lesions or plaques. Some plaques become thrombosis-prone and rupture, causing
      acute myocardial infarction or stroke. Lowering plasma cholesterol through the
      use of statins is the primary intervention against atherosclerosis. Treatment
      with statins slows progression of atherosclerosis but can only support limited
      plaque regression. Partially regressed plaques continue to pose a serious threat
      due to their remaining potential to rupture. Thus, new interventions inducing
      complete reversal of atherosclerosis are being sought. Implementation of new
      therapies will require clear understanding of the mechanisms driving plaque
      resolution. In this Views and Commentary, we highlight the role of bone marrow
      endothelial progenitors in atherosclerotic plaque regression and discuss how
      regenerative cell-based interventions could be used in combination with plasma
      lipid-lowering to induce plaque reversal in order to prevent and/or reduce
      adverse cardiovascular events.

PMID- 23538779
TI  - Accuracy of clinical skin tumour diagnosis in a dermatological setting.
AB  - The aim of this study was to evaluate the accuracy of preoperative diagnosis of
      skin tumours in a dermatological setting. Patients undergoing skin surgery at the
      Department of Dermatology without preoperative biopsy were prospectively
      enrolled. Preoperatively, a single clinical diagnosis was registered. The
      histopathological diagnosis, performed after excision, was registered as the
      correct diagnosis. The sensitivity and positive predictive value of the clinical
      diagnosis were calculated. A total of 2,953 tumours were included. Altogether,
      55.1% of the excised lesions were malignant. Excision margins for malignant
      tumours were free from tumour cells in 96.0% of cases. The sensitivity for
      diagnosis of malignant tumour was 98.0% and the positive predictive value was
      85.3%. In line with previous studies, the sensitivity and positive predictive
      value were highest for basal cell carcinoma, 95.4% and 85.9%, respectively. For
      squamous cell carcinoma, the corresponding values were 68.0% and 67.3%, and for
      melanoma, 70.6% and 51.3%.

PMID- 23538780
TI  - BF3.OEt2-Promoted Concise Synthesis of Difluoroboron-Derivatized Curcumins from
      Aldehydes and 2,4-Pentanedione.
AB  - A concise and one-pot cascade method has been developed to achieve the synthesis
      of difluoroboron-derivatized curcumins (BF2C). Treatment of 2,4-pentanedione with
      BF3.OEt2, followed by condensation with aldehydes in the presence of tributyl
      borate and butylamine at 65  degrees C in toluene furnished the corresponding
      symmetric (s-BF2C) and unsymmetric difluoroboron-derivatized curcumins (us-BF2C)
      in good (60 - 99%) and moderate yields (23 - 42%) within 6 - 12 h, respectively.

PMID- 23538781
TI  - Cytochrome b gene (cytb) sequence diversity in a Microtus oeconomus population
      from Bialowieza Primeval Forest.
AB  - Based on published information about the glacial, postglacial, and recent
      distribution of the root vole, Microtus oeconomus, we hypothesized that a
      population inhabiting the pristine wetland in eastern Poland (Bialowieza Primeval
      Forest) might comprise a high diversity of haplotypes. The support for this
      hypothesis was provided by an analysis of partial cytb gene sequences from 149
      voles sampled within a two-hectare plot during a nine-year study. In this
      population, we identified eight haplotypes (PLB1-PLB8), four of which were new to
      the root vole. These haplotypes were characterized by low nucleotide diversity
      (pi = 0.0054, SE = 0.0019), the absence of transversional differences between
      sequences, and no changes in the encoded amino acid sequence: features suggesting
      a lack of immigration from the distant populations. The haplotype number and
      their frequency distribution in males and females did not differ significantly.
      An assessment of the persistence of matrilines in the local population throughout
      the study period revealed that the haplotype composition was relatively stable
      for only about 3 years. A more complete haplotype network for root voles in
      Europe was constructed by combining the newly identified haplotypes with the 45
      previously described haplotypes. Two of the haplotypes detected in this study
      occupy key positions in this network: PLB5, as the closest link to the North
      European group, and PLB8, as an ancestor to many other Central European
      haplotypes.

PMID- 23538782
TI  - Subcapsular hepatic haematoma after endoscopic retrograde
      cholangiopancreatography: an unusual case.
AB  - Subcapsular hepatic haematoma is a rare complication of endoscopic retrograde
      cholangiopancreatography (ERCP), and there are few reports about this unusual
      complication worldwide. The primary symptom of most cases reported in the
      literature is abdominal pain. We report an unusual case with the primary symptom
      of fever. A 56-year-old man who had a six-month history of recurrent episodes of
      upper abdominal pain was diagnosed with a common bile duct stone by magnetic
      resonance cholangiopancreatography. Endoscopic biliary sphincterotomy was
      performed, and stones from the common bile duct were successfully extracted with
      a basket. The patient had a persistent fever after ERCP, and treatment with
      intravenous antibiotics was unsuccessful. Computed tomography showed a 13 cm * 6
      cm subcapsular hepatic haematoma filled with air and liquid on the surface of the
      right hepatic lobe. The patient was successfully treated with peritoneal drainage
      under B-ultra guidance. Subcapsular liver haematoma should be considered when
      hard-to- explain symptoms persist in the early period after ERCP. Percutaneous
      drainage is an effective treatment.

PMID- 23538783
TI  - Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the
      lower airways in COPD.
AB  - BACKGROUND: Cigarette smoke and smoking-induced inflammation decrease cystic
      fibrosis transmembrane conductance regulator (CFTR) activity and mucociliary
      transport in the nasal airway and cultured bronchial epithelial cells. This
      raises the possibility that lower airway CFTR dysfunction may contribute to the
      pathophysiology of COPD. We compared lower airway CFTR activity in current and
      former smokers with COPD, current smokers without COPD, and lifelong nonsmokers
      to examine the relationships between clinical characteristics and CFTR expression
      and function. METHODS: Demographic, spirometry, and symptom questionnaire data
      were collected. CFTR activity was determined by nasal potential difference (NPD)
      and lower airway potential difference (LAPD) assays. The primary measure of CFTR
      function was the total change in chloride transport (Deltachloride-free
      isoproterenol). CFTR protein expression in endobronchial biopsy specimens was
      measured by Western blot. RESULTS: Compared with healthy nonsmokers (n = 11),
      current smokers (n = 17) showed a significant reduction in LAPD CFTR activity
      (Deltachloride-free isoproterenol, -8.70 mV vs -15.9 mV; P = .003). Similar
      reductions were observed in smokers with and without COPD. Former smokers with
      COPD (n = 7) showed a nonsignificant reduction in chloride conductance (-12.7
      mV). A similar pattern was observed for CFTR protein expression. Univariate
      analysis demonstrated correlations between LAPD CFTR activity and current
      smoking, the presence of chronic bronchitis, and dyspnea scores. CONCLUSIONS:
      Smokers with and without COPD have reduced lower airway CFTR activity compared
      with healthy nonsmokers, and this finding correlates with disease phenotype.
      Acquired CFTR dysfunction may contribute to COPD pathogenesis.

PMID- 23538784
TI  - Endoscopic ultrasonography guided biliary drainage: summary of consortium
      meeting, May 7th, 2011, Chicago.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has become the preferred
      procedure for biliary or pancreatic drainage in various pancreatico-biliary
      disorders. With a success rate of more than 90%, ERCP may not achieve biliary or
      pancreatic drainage in cases with altered anatomy or with tumors obstructing
      access to the duodenum. In the past those failures were typically managed
      exclusively by percutaneous approaches by interventional radiologists or surgical
      intervention. The morbidity associated was significant especially in those
      patients with advanced malignancy, seeking minimally invasive interventions and
      improved quality of life. With the advent of biliary drainage via endoscopic
      ultrasound (EUS) guidance, EUS guided biliary drainage has been used more
      frequently within the last decade in different countries. As with any novel
      advanced endoscopic procedure that encompasses various approaches, advanced
      endoscopists all over the world have innovated and adopted diverse EUS guided
      biliary and pancreatic drainage techniques. This diversity has resulted in
      variations and improvements in EUS Guided biliary and pancreatic drainage; and
      over the years has led to an extensive nomenclature. The diversity of techniques,
      nomenclature and recent progress in our intrumentation has led to a dedicated
      meeting on May 7(th), 2011 during Digestive Disease Week 2011. More than 40
      advanced endoscopists from United States, Brazil, Mexico, Venezuela, Colombia,
      Italy, France, Austria, Germany, Spain, Japan, China, South Korea and India
      attended this pivotal meeting. The meeting covered improved EUS guided biliary
      access and drainage procedures, terminology, nomenclature, training and
      credentialing; as well as emerging devices for EUS guided biliary drainage. This
      paper summarizes the meeting's agenda and the conclusions generated by the
      creation of this consortium group.

PMID- 23538786
TI  - Activation of E-Cl bonds (E = C, Si, Ge and Sn) by a C,N-chelated stannylene.
AB  - The reactivity of (L(CN))(2)Sn (1) (where L(CN) is 2-(N,N
      dimethylaminomethyl)phenyl-) towards various substrates containing E-Cl bond(s)
      has been studied (E = C, Si, Ge and Sn). Alkyl chlorides like chloroform or
      dichloromethane reacts with 1 to form (L(CN))(2)SnCl(2) and unidentified by
      products in poor yields. The reaction of benzoyl chloride with 1 at low
      temperature yielded a thermally unstable product (L(CN))(2)Sn(Cl)C(O)Ph (2) which
      was isolated and characterized by both multinuclear NMR spectroscopy and X-ray
      diffraction techniques. The vicinity of the central tin atom in 2 reveals
      trigonal bipyramidal geometry. Attempts to oxidize 2 by dioxygen to give the
      corresponding organotin(IV) benzoate failed. On the other hand, the reaction of
      the in situ prepared (L(CN))(2)Sn=O (synthesized by the reaction of 1 with
      dioxygen) with PhCOCl resulted in the formation of the desired organotin(IV)
      benzoate (L(CN))(2)Sn(Cl)C(=O)OPh (3). The reaction of 1 with Ph3GeCl yielded
      triphenylgermyl-substituted diorganotin(IV) chloride (L(CN))(2)Sn(Cl)GePh(3) (4)
      which subsequently gave mixed diorganotin(IV) chloride-oxide [(L(CN))(2)SnCl](2)O
      (5) upon loss of the GePh(3) moiety in the air. When the same reaction was
      carried out in benzene instead of chloroform a unique [Ph(3)Ge](4)[Sn(6)O(8)]
      cluster (6) was obtained. Similarly, the reaction of 1 with Ph3SiCl provided
      triphenylsilyl-substituted diorganotin(IV) chloride (L(CN))(2)Sn(Cl)SiPh(3) (7)
      which was then oxidized to (L(CN))(2)Sn(Cl)OSiPh(3) (8). The unprecedented
      reaction of 1 with (n-Bu)(3)SnCl provided the distannane (L(CN))(2)Sn(Cl)SnBu(3)
      (9) which could be oxidized by dioxygen to a distannoxane
      (L(CN))(2)Sn(Cl)OSnBu(3) (10). In addition, the solid-state structures of 3, 5, 6
      and 8 were determined by the X-ray diffraction techniques.

PMID- 23538785
TI  - Exploiting Acyl and Enol Azolium Intermediates via NHeterocyclic Carbene
      Catalyzed Reactions of Alpha-Reducible Aldehydes.
AB  - N-heterocyclic carbenes are well known for their role in catalyzing benzoin and
      Stetter reactions: the generation of acyl anion equivalents from simple aldehydes
      to react with a variety of electrophiles. However, when an aldehyde bearing a
      leaving group or unsaturation adjacent to the acyl anion equivalent is subjected
      to an NHC, a new avenue of reactivity is unlocked, leading to a number of novel
      transformations which can generate highly complex products from simple starting
      materials, many of which are assembled through unconventional bond
      disconnections. The field of these new reactions - those utilizing alpha
      reducible aldehydes to access previously unexplored catalytic intermediates - has
      expanded rapidly in the past eight years. This review aims to provide the reader
      with a historical perspective on the underlying discoveries that led to the
      current state of the art, a mechanistic description of these reactions, and a
      summary of the recent advances in this area.

PMID- 23538787
TI  - Synthesis of the IGF-II-like hormone vesiculin using regioselective formation of
      disulfide bonds.
AB  - Diabetes mellitus, characterised by hyperglycemia and altered beta-cell function,
      is an increasingly common disorder affecting millions of individuals world-wide.
      While therapeutic regimens exist to manage the condition, diabetic individuals
      remain prone to complications that are detrimental to both their length and
      quality of life. An improved understanding of the disease which may then enable
      development of new treatments is therefore a desirable goal. Vesiculin, a novel
      IGF-II-like protein was recently isolated from the secretory granules of murine
      beta-cells, and preliminary studies indicate it is capable of signalling via the
      insulin receptor (IR)/insulin-like growth factor receptor 1(IGF1R) family giving
      it the potential to elicit both metabolic and mitogenic responses in the beta
      cell. In order to facilitate further studies on this new member of the insulin
      family of hormones, we undertook a chemical synthesis of the protein using
      regioselective disulfide bond formation.

PMID- 23538789
TI  - H5N1 viral-engineering dangers will not go away.

PMID- 23538788
TI  - Cognitive functioning and depressive symptoms in adolescents with inflammatory
      bowel disease.
AB  - AIM: To investigate cognitive functioning and depressive symptoms in adolescents
      with inflammatory bowel disease (IBD). METHODS: A neuropsychological test
      battery, including subtests of the Wechsler Adult Intelligence Scale-Revised and
      III, Wechsler Memory Scale-Revised, California Verbal Learning Test (CVLT),
      Stroop Color-Word Test, and Trail Making Test, which assessed verbal and visual
      short- and long-term memory, processing speed, logical reasoning, verbal
      intelligence, attention, and executive functioning, was administered to 13- to 19
      year-old patients with IBD (n = 34; active disease n = 20). Depressive symptoms
      were measured with the Beck Depression Inventory. The findings were compared with
      peers with non-acute juvenile idiopathic arthritis (JIA; n = 23). Patients with
      coexisting psychiatric disorders were excluded. RESULTS: The IBD group,
      especially patients in the acute phase, made more perseverative errors in the
      CVLT test that assessed verbal memory than the JIA group (6.0 +/- 4.3 vs 3.3 +/-
      2.9, P < 0.01), but no other differences between the IBD and JIA groups were
      observed in the neuropsychological tests. The difference was close to statistical
      significance, even when glucocorticoid medication was controlled for (P < 0.052).
      The IBD group had more depressive symptoms than the JIA group (7.9 +/- 7.6 vs 4.0
      +/- 4.0, P < 0.05). Approximately one third of the IBD group had at least mild
      depressive symptoms, and those with acute illness had the highest scores.
      However, depressive symptoms were not related to the difference in the verbal
      memory test (perseverative errors in the CVLT) between the IBD and JIA groups.
      CONCLUSION: Adolescents with acute IBD may have mild verbal memory problems but
      no major cognitive deficits compared to peers with JIA.

PMID- 23538800
TI  - Planck snaps infant Universe.

PMID- 23538801
TI  - Stem-cell ruling riles researchers.

PMID- 23538802
TI  - Drug-company data vaults to be opened.

PMID- 23538803
TI  - Private research ship makes waves.

PMID- 23538804
TI  - Sham journals scam authors.

PMID- 23538805
TI  - Higgs physics on the cheap.

PMID- 23538807
TI  - The future of publishing: A new page.

PMID- 23538808
TI  - Open access: The true cost of science publishing.

PMID- 23538809
TI  - Publishing frontiers: The library reboot.

PMID- 23538810
TI  - Investigating journals: The dark side of publishing.

PMID- 23538811
TI  - Scholarship: Beyond the paper.

PMID- 23538812
TI  - Licence restrictions: A fool's errand.

PMID- 23538813
TI  - Advocacy: How to hasten open access.

PMID- 23538817
TI  - Q&A: Knowledge liberator. Interview by Jascha Hoffman.

PMID- 23538818
TI  - Research conduct: Online integrity training falls short.

PMID- 23538820
TI  - Radioactive dumping: Nuclear-waste site geology is paramount.

PMID- 23538819
TI  - Health metrics: Standardize records of place of death.

PMID- 23538823
TI  - Robert Richardson (1937-2013).

PMID- 23538821
TI  - Research ethics: Too much reliance on anonymous tip-offs.

PMID- 23538824
TI  - Global health: Persuasive evidence on HIV policy.

PMID- 23538825
TI  - Materials science: Nanoparticle structures served up on a tray.

PMID- 23538826
TI  - Earth science: How the ocean exhales.

PMID- 23538827
TI  - X-ray crystallography: One size fits most.

PMID- 23538828
TI  - X-ray analysis on the nanogram to microgram scale using porous complexes.
AB  - X-ray single-crystal diffraction (SCD) analysis has the intrinsic limitation that
      the target molecules must be obtained as single crystals. Here we report a
      protocol for SCD analysis that does not require the crystallization of the
      sample. In our method, tiny crystals of porous complexes are soaked in a solution
      of the target, such that the complexes can absorb the target molecules.
      Crystallographic analysis clearly determines the absorbed guest structures along
      with the host frameworks. Because the SCD analysis is carried out on only one
      tiny crystal of the complex, the required sample mass is of the nanogram
      microgram order. We demonstrate that as little as about 80 nanograms of a sample
      is enough for the SCD analysis. In combination with high-performance liquid
      chromatography, our protocol allows the direct characterization of multiple
      fractions, establishing a prototypical means of liquid chromatography SCD
      analysis. Furthermore, we unambiguously determined the structure of a scarce
      marine natural product using only 5 micrograms of the compound.

PMID- 23538829
TI  - Carbon monoxide in clouds at low metallicity in the dwarf irregular galaxy WLM.
AB  - Carbon monoxide (CO) is the primary tracer for interstellar clouds where stars
      form, but it has never been detected in galaxies in which the oxygen abundance
      relative to hydrogen is less than 20 per cent of that of the Sun, even though
      such 'low-metallicity' galaxies often form stars. This raises the question of
      whether stars can form in dense gas without molecules, cooling to the required
      near-zero temperatures by atomic transitions and dust radiation rather than by
      molecular line emission; and it highlights uncertainties about star formation in
      the early Universe, when the metallicity was generally low. Here we report the
      detection of CO in two regions of a local dwarf irregular galaxy, WLM, where the
      metallicity is 13 per cent of the solar value. We use new submillimetre
      observations and archival far-infrared observations to estimate the cloud masses,
      which are both slightly greater than 100,000 solar masses. The clouds have
      produced stars at a rate per molecule equal to 10 per cent of that in the local
      Orion nebula cloud. The CO fraction of the molecular gas is also low, about 3 per
      cent of the Milky Way value. These results suggest that in small galaxies both
      star-forming cores and CO molecules become increasingly rare in molecular
      hydrogen clouds as the metallicity decreases.

PMID- 23538830
TI  - Evidence for sympathetic vibrational cooling of translationally cold molecules.
AB  - Compared with atoms, molecules have a rich internal structure that offers many
      opportunities for technological and scientific advancement. The study of this
      structure could yield critical insights into quantum chemistry, new methods for
      manipulating quantum information, and improved tests of discrete symmetry
      violation and fundamental constant variation. Harnessing this potential typically
      requires the preparation of cold molecules in their quantum rovibrational ground
      state. However, the molecular internal structure severely complicates efforts to
      produce such samples. Removal of energy stored in long-lived vibrational levels
      is particularly problematic because optical transitions between vibrational
      levels are not governed by strict selection rules, which makes laser cooling
      difficult. Additionally, traditional collisional, or sympathetic, cooling methods
      are inefficient at quenching molecular vibrational motion. Here we experimentally
      demonstrate that the vibrational motion of trapped BaCl(+) molecules is quenched
      by collisions with ultracold calcium atoms at a rate comparable to the classical
      scattering, or Langevin, rate. This is over four orders of magnitude more
      efficient than traditional sympathetic cooling schemes. The high cooling rate, a
      consequence of a strong interaction potential (due to the high polarizability of
      calcium), along with the low collision energies involved, leads to molecular
      samples with a vibrational ground-state occupancy of at least 90 per cent. Our
      demonstration uses a novel thermometry technique that relies on relative
      photodissociation yields. Although the decrease in vibrational temperature is
      modest, with straightforward improvements it should be possible to produce
      molecular samples with a vibrational ground-state occupancy greater than 99 per
      cent in less than 100 milliseconds. Because sympathetic cooling of molecular
      rotational motion is much more efficient than vibrational cooling in traditional
      systems, we expect that the method also allows efficient cooling of the
      rotational motion of the molecules. Moreover, the technique should work for many
      different combinations of ultracold atoms and molecules.

PMID- 23538831
TI  - Deglacial pulses of deep-ocean silicate into the subtropical North Atlantic
      Ocean.
AB  - Growing evidence suggests that the low atmospheric CO2 concentration of the ice
      ages resulted from enhanced storage of CO2 in the ocean interior, largely as a
      result of changes in the Southern Ocean. Early in the most recent deglaciation, a
      reduction in North Atlantic overturning circulation seems to have driven CO2
      release from the Southern Ocean, but the mechanism connecting the North Atlantic
      and the Southern Ocean remains unclear. Biogenic opal export in the low-latitude
      ocean relies on silicate from the underlying thermocline, the concentration of
      which is affected by the circulation of the ocean interior. Here we report a
      record of biogenic opal export from a coastal upwelling system off the coast of
      northwest Africa that shows pronounced opal maxima during each glacial
      termination over the past 550,000 years. These opal peaks are consistent with a
      strong deglacial reduction in the formation of silicate-poor glacial North
      Atlantic intermediate water (GNAIW). The loss of GNAIW allowed mixing with
      underlying silicate-rich deep water to increase the silicate supply to the
      surface ocean. An increase in westerly-wind-driven upwelling in the Southern
      Ocean in response to the North Atlantic change has been proposed to drive the
      deglacial rise in atmospheric CO2 (refs 3, 4). However, such a circulation change
      would have accelerated the formation of Antarctic intermediate water and sub
      Antarctic mode water, which today have as little silicate as North Atlantic Deep
      Water and would have thus maintained low silicate concentrations in the Atlantic
      thermocline. The deglacial opal maxima reported here suggest an alternative
      mechanism for the deglacial CO2 release. Just as the reduction in GNAIW led to
      upward silicate transport, it should also have allowed the downward mixing of
      warm, low-density surface water to reach into the deep ocean. The resulting
      decrease in the density of the deep Atlantic relative to the Southern Ocean
      surface promoted Antarctic overturning, which released CO2 to the atmosphere.

PMID- 23538832
TI  - Electrical image of passive mantle upwelling beneath the northern East Pacific
      Rise.
AB  - Melt generated by mantle upwelling is fundamental to the production of new
      oceanic crust at mid-ocean ridges, yet the forces controlling this process are
      debated. Passive-flow models predict symmetric upwelling due to viscous drag from
      the diverging tectonic plates, but have been challenged by geophysical
      observations of asymmetric upwelling that suggest anomalous mantle pressure and
      temperature gradients, and by observations of concentrated upwelling centres
      consistent with active models where buoyancy forces give rise to focused
      convective flow. Here we use sea-floor magnetotelluric soundings at the fast
      spreading northern East Pacific Rise to image mantle electrical structure to a
      depth of about 160 kilometres. Our data reveal a symmetric, high-conductivity
      region at depths of 20-90 kilometres that is consistent with partial melting of
      passively upwelling mantle. The triangular region of conductive partial melt
      matches passive-flow predictions, suggesting that melt focusing to the ridge
      occurs in the porous melting region rather than along the shallower base of the
      thermal lithosphere. A deeper conductor observed east of the ridge at a depth of
      more than 100 kilometres is explained by asymmetric upwelling due to viscous
      coupling across two nearby transform faults. Significant electrical anisotropy
      occurs only in the shallowest mantle east of the ridge axis, where high vertical
      conductivity at depths of 10-20 kilometres indicates localized porous conduits.
      This suggests that a coincident seismic-velocity anomaly is evidence of shallow
      magma transport channels rather than deeper off-axis upwelling. We interpret the
      mantle electrical structure as evidence that plate-driven passive upwelling
      dominates this ridge segment, with dynamic forces being negligible.

PMID- 23538833
TI  - Accelerated gene evolution through replication-transcription conflicts.
AB  - Several mechanisms that increase the rate of mutagenesis across the entire genome
      have been identified; however, how the rate of evolution might be promoted in
      individual genes is unclear. Most genes in bacteria are encoded on the leading
      strand of replication. This presumably avoids the potentially detrimental head-on
      collisions that occur between the replication and transcription machineries when
      genes are encoded on the lagging strand. Here we identify the ubiquitous (core)
      genes in Bacillus subtilis and determine that 17% of them are on the lagging
      strand. We find a higher rate of point mutations in the core genes on the lagging
      strand compared with those on the leading strand, with this difference being
      primarily in the amino-acid-changing (nonsynonymous) mutations. We determine
      that, overall, the genes under strong negative selection against amino-acid
      changing mutations tend to be on the leading strand, co-oriented with
      replication. In contrast, on the basis of the rate of convergent mutations, genes
      under positive selection for amino-acid-changing mutations are more commonly
      found on the lagging strand, indicating faster adaptive evolution in many genes
      in the head-on orientation. Increased gene length and gene expression amounts are
      positively correlated with the rate of accumulation of nonsynonymous mutations in
      the head-on genes, suggesting that the conflict between replication and
      transcription could be a driving force behind these mutations. Indeed, using
      reversion assays, we show that the difference in the rate of mutagenesis of genes
      in the two orientations is transcription dependent. Altogether, our findings
      indicate that head-on replication-transcription conflicts are more mutagenic than
      co-directional conflicts and that these encounters can significantly increase
      adaptive structural variation in the coded proteins. We propose that bacteria,
      and potentially other organisms, promote faster evolution of specific genes
      through orientation-dependent encounters between DNA replication and
      transcription.

PMID- 23538835
TI  - Is the ocean food provision index biased?

PMID- 23538837
TI  - Nondestructive Monitoring of the Repair of Natural Occlusal Lesions using Cross -
      Polarization Optical Coherence Tomography.
AB  - Previous remineralization studies employing cross polarization sensitive optical
      coherence tomography (CP-OCT), have been limited to the repair of artificial
      enamel-like lesions. In this study we attempted to remineralize existing occlusal
      lesions on extracted teeth. Lesions were imaged before and after exposure to an
      acidic remineralization regimen and the integrated reflectivity and lesion depth
      was calculated. Automated integration routines worked well for assessing the
      integrated reflectivity for the lesion areas after remineralization. Polarized
      light microscopy was also used to examine the lesions areas after sectioning the
      teeth. An acidic remineralization solution was used to remineralize the lesions.
      The integrated reflectivity significantly increased after exposure to the
      remineralization solution which suggests that the acidic solution caused
      additional demineralization as opposed to the desired remineralization.

PMID- 23538838
TI  - Selective pumping in a network: insect-style microscale flow transport.
AB  - A new paradigm for selective pumping of fluids in a complex network of channels
      in the microscale flow regime is presented. The model is inspired by internal
      flow distributions produced by the rhythmic wall contractions observed in many
      insect tracheal networks. The approach presented here is a natural extension of
      previous two-dimensional modeling of insect-inspired microscale flow transport in
      a single channel, and aims to manipulate fluids efficiently in microscale
      networks without the use of any mechanical valves. This selective pumping
      approach enables fluids to be transported, controlled and precisely directed into
      a specific branch in a network while avoiding other possible routes. In order to
      present a quantitative analysis of the selective pumping approach presented here,
      the velocity and pressure fields and the time-averaged net flow that are induced
      by prescribed wall contractions are calculated numerically using the method of
      fundamental solutions. More specifically, the Stokeslets-meshfree method is used
      in this study to solve the Stokes equations that govern the flow motions in a
      network with moving wall contractions. The results presented here might help in
      understanding some features of the insect respiratory system function and guide
      efforts to fabricate novel microfluidic devices for flow transport and mixing,
      and targeted drug delivery applications.

PMID- 23538839
TI  - Genetic diversity revealed by single nucleotide polymorphism markers in a
      worldwide germplasm collection of durum wheat.
AB  - Evaluation of genetic diversity and genetic structure in crops has important
      implications for plant breeding programs and the conservation of genetic
      resources. Newly developed single nucleotide polymorphism (SNP) markers are
      effective in detecting genetic diversity. In the present study, a worldwide durum
      wheat collection consisting of 150 accessions was used. Genetic diversity and
      genetic structure were investigated using 946 polymorphic SNP markers covering
      the whole genome of tetraploid wheat. Genetic structure was greatly impacted by
      multiple factors, such as environmental conditions, breeding methods reflected by
      release periods of varieties, and gene flows via human activities. A loss of
      genetic diversity was observed from landraces and old cultivars to the modern
      cultivars released during periods of the Early Green Revolution, but an increase
      in cultivars released during the Post Green Revolution. Furthermore, a
      comparative analysis of genetic diversity among the 10 mega ecogeographical
      regions indicated that South America, North America, and Europe possessed the
      richest genetic variability, while the Middle East showed moderate levels of
      genetic diversity.

PMID- 23538840
TI  - Roles of rho GTPases in intracellular transport and cellular transformation.
AB  - Rho family GTPases belong to the Ras GTPase superfamily and transduce
      intracellular signals known to regulate a variety of cellular processes,
      including cell polarity, morphogenesis, migration, apoptosis, vesicle
      trafficking, viral transport and cellular transformation. The three best
      characterized Rho family members are Cdc42, RhoA and Rac1. Cdc42 regulates
      endocytosis, the transport between the endoplasmic reticulum and Golgi apparatus,
      post-Golgi transport and exocytosis. Cdc42 influences trafficking through
      interaction with Wiskott-Aldrich syndrome protein (N-WASP) and the Arp2/3
      complex, leading to changes in actin dynamics. Rac1 mediates endocytic and
      exocytic vesicle trafficking by interaction with its effectors, PI3kinase,
      synaptojanin 2, IQGAP1 and phospholipase D1. RhoA participates in the regulation
      of endocytosis through controlling its downstream target, Rho kinase.
      Interestingly, these GTPases play important roles at different stages of viral
      protein and genome transport in infected host cells. Importantly, dysregulation
      of Cdc42, Rac1 and RhoA leads to numerous disorders, including malignant
      transformation. In some cases, hyperactivation of Rho GTPases is required for
      cellular transformation. In this article, we review a number of findings related
      to Rho GTPase function in intracellular transport and cellular transformation.

PMID- 23538842
TI  - Effect of Opuntia humifusa supplementation and acute exercise on insulin
      sensitivity and associations with PPAR-gamma and PGC-1alpha protein expression in
      skeletal muscle of rats.
AB  - This study examined whether Opuntia humifusa (O. humifusa), which is a member of
      the Cactaceae family, supplementation and acute swimming exercise affect insulin
      sensitivity and associations with PPAR-gamma and PGC-1alpha protein expression in
      rats. Thirty-two rats were randomly divided into four groups (HS: high fat diet
      sedentary group, n = 8; HE: high fat diet acute exercise group, n = 8; OS: 5% O.
      humifusa supplemented high fat diet sedentary group, n = 8; OE: 5% O. humifusa
      supplemented high fat diet acute exercise group, n = 8). Rats in the HE and OE
      swam for 120 min. before being sacrificed. Our results indicated that serum
      glucose level, fasting insulin level and homeostasis model assessment of insulin
      resistance (HOMA-IR) in OS were significantly lower compared to those of the HS
      (p < 0.01, p < 0.05, p < 0.05). In addition, PPAR-gamma protein expression in the
      OS and OE was significantly higher than that of the HS and HE, respectively (p <
      0.05, p < 0.01). PGC-1alpha and GLUT-4 protein expressions in the OS were
      significantly higher compared to those of the HS (p < 0.05, p < 0.05). From these
      results, O. humifusa supplementation might play an important role for improving
      insulin sensitivity through elevation of PPAR-gamma, PGC-1alpha, and GLUT-4
      protein expression in rat skeletal muscle.

PMID- 23538841
TI  - Skeletal muscle function during exercise-fine-tuning of diverse subsystems by
      nitric oxide.
AB  - Skeletal muscle is responsible for altered acute and chronic workload as induced
      by exercise. Skeletal muscle adaptations range from immediate change of
      contractility to structural adaptation to adjust the demanded performance
      capacities. These processes are regulated by mechanically and metabolically
      induced signaling pathways, which are more or less involved in all of these
      regulations. Nitric oxide is one of the central signaling molecules involved in
      functional and structural adaption in different cell types. It is mainly produced
      by nitric oxide synthases (NOS) and by non-enzymatic pathways also in skeletal
      muscle. The relevance of a NOS-dependent NO signaling in skeletal muscle is
      underlined by the differential subcellular expression of NOS1, NOS2, and NOS3,
      and the alteration of NO production provoked by changes of workload. In skeletal
      muscle, a variety of highly relevant tasks to maintain skeletal muscle integrity
      and proper signaling mechanisms during adaptation processes towards mechanical
      and metabolic stimulations are taken over by NO signaling. The NO signaling can
      be mediated by cGMP-dependent and -independent signaling, such as S-nitrosylation
      dependent modulation of effector molecules involved in contractile and metabolic
      adaptation to exercise. In this review, we describe the most recent findings of
      NO signaling in skeletal muscle with a special emphasis on exercise conditions.
      However, to gain a more detailed understanding of the complex role of NO
      signaling for functional adaptation of skeletal muscle (during exercise),
      additional sophisticated studies are needed to provide deeper insights into NO
      mediated signaling and the role of non-enzymatic-derived NO in skeletal muscle
      physiology.

PMID- 23538843
TI  - Transcriptional analysis of drought-induced genes in the roots of a tolerant
      genotype of the common bean (Phaseolus vulgaris L.).
AB  - In Brazil, common bean (Phaseolus vulgaris L.) productivity is severely affected
      by drought stress due to low technology cultivation systems. Our purpose was to
      identify differentially expressed genes in roots of a genotype tolerant to water
      deficit (BAT 477) when submitted to an interruption of irrigation during its
      development. A SSH library was constructed taking as "driver" the genotype
      Carioca 80SH (susceptible to drought). After clustering and data mining, 1572
      valid reads were obtained, resulting in 1120 ESTs (expressed sequence tags). We
      found sequences for transcription factors, carbohydrates metabolism, proline-rich
      proteins, aquaporins, chaperones and ubiquitins, all of them organized according
      to their biological processes. Our suppressive subtractive hybridization (SSH)
      library was validated through RT-qPCR experiment by assessing the expression
      patterns of 10 selected genes in both genotypes under stressed and control
      conditions. Finally, the expression patterns of 31 ESTs, putatively related to
      drought responses, were analyzed in a time-course experiment. Our results
      confirmed that such genes are more expressed in the tolerant genotype during
      stress; however, they are not exclusive, since different levels of these
      transcripts were also detected in the susceptible genotype. In addition, we
      observed a fluctuation in gene regulation over time for both the genotypes, which
      seem to adopt and adapt different strategies in order to develop tolerance
      against this stress.

PMID- 23538844
TI  - Cadmium tolerance and removal from Cunninghamella elegans related to the
      polyphosphate metabolism.
AB  - The aim of the present work was to study the cadmium effects on growth,
      ultrastructure and polyphosphate metabolism, as well as to evaluate the metal
      removal and accumulation by Cunninghamella elegans (IFM 46109) growing in culture
      medium. The presence of cadmium reduced growth, and a longer lag phase was
      observed. However, the phosphate uptake from the culture medium increased 15%
      when compared to the control. Moreover, C. elegans removed 70%-81% of the cadmium
      added to the culture medium during its growth. The C. elegans mycelia showed a
      removal efficiency of 280 mg/g at a cadmium concentration of 22.10 mg/L, and the
      removal velocity of cadmium was 0.107 mg/h. Additionally, it was observed that
      cadmium induced vacuolization, the presence of electron dense deposits in
      vacuoles, cytoplasm and cell membranes, as well as the distinct behavior of
      polyphosphate fractions. The results obtained with C. elegans suggest that
      precipitation, vacuolization and polyphosphate fractions were associated to
      cadmium tolerance, and this species demonstrated a higher potential for
      bioremediation of heavy metals.

PMID- 23538845
TI  - Manifold benefits of choosing a minimally fluoroscopic catheter ablation
      approach.
AB  - We report the case of a 14-year-old boy with ventricular preexcitation. A
      standard, fluoroscopy guided, ablation procedure was successfully performed in a
      postero-midseptal region with a total fluoroscopy time of about 45 min (2430
      cGy.cm(2)). A few hours after the procedure, preexcitation reappeared. A second
      ablation procedure was scheduled using the EnSite NavXTM mapping system. During
      mapping along the tricuspid groove, preexcitation suddenly disappeared due to
      mechanical "bumping" of the accessory pathway and it did not recover over the
      next 30 min. As per our routine practice, the phase of geometry reconstruction
      has been continuously recorded by the system; thus, an off-line analysis allowed
      to pinpoint the site of earliest activation and the site of mechanical bumping,
      where radiofrequency obtained the accessory pathway ablation. The second
      procedure was performed without using fluoroscopy at all. Thanks to the geometry
      reconstruction, the procedure was completely successful thus avoiding a further
      rehospitalization.

PMID- 23538846
TI  - Evaluation of an improved bioluminescence assay for the detection of bacteria in
      soy milk.
AB  - Because soy milk is nutrient rich and nearly neutral in pH, it favors the growth
      of microbial contaminants. To ensure that soy milk meets food-safety standards,
      it must be pasteurized and have its sterility confirmed. ATP bioluminescence
      assay has become a widely accepted means of detecting food microorganisms.
      However, the high background bioluminescence intensity of soy milk has rendered
      it unsuitable for ATP analysis. Here, we tested the efficacy of an improved pre
      treated bioluminescence assay on soy milk. By comparing background
      bioluminescence intensities obtained by the conventional and improved methods, we
      demonstrated that our method significantly reduces soy milk background
      bioluminescence. The dose-response curve of the assay was tested with serial
      dilutions of Bacillus sp. culture. An extremely strong log-linear relation
      between the bioluminescence intensity relative light units and colony formation
      units CFU/ml emerged for the tested strain. The detection limit of the assay was
      estimated as 5.2*10(3) CFU/ml from the dose-response curve and an imposed signal
      limit was three times the background level. The results showed that contaminated
      samples could be easily detected within 24 h using our improved bioluminescence
      assay.

PMID- 23538847
TI  - Confirmation of the sterilization effect using a high concentration of ozone gas
      for the bio-clean room.
AB  - A high-level aseptic environment must be maintained in bio-cleanrooms used for
      the manufacture of sterile products. In the past, formaldehyde gas was most
      commonly used to sterilize bio-cleanrooms, but due to strict residual limitations
      there has been a need to develop a less toxic alternative choice. The authors
      have developed a revolutionary new sterilization system using a high
      concentration of ozone gas and used this system to sterilize an actual bio
      cleanroom. This system integrates the ozone gas generator with the air
      conditioning system by proper control. The design specifications for the system
      included an ozone gas concentration of 200 ppm or more, relative humidity of 80%
      or more, and a sterilizing time of 120 min. Blow vents and suction ports were
      placed to ensure a uniform airflow which would extend through the entire room
      during ozone gas sterilization. Tests regarding long-term material exposure to
      ozone gas were conducted when the system was introduced to distinguish usable and
      unusable materials. In an actually constructed cleanroom, simulations were used
      to predict the evenness of the diffusion of ozone gas concentration and relative
      humidity during ozone gas sterilization, and measurements of the actual indoor
      ozone gas concentration, temperature and relative humidity during sterilization
      revealed that the ozone concentration and relative humidity needed for
      sterilization had been achieved generally throughout the entire environment. In
      addition, the CT value (mg/m(3) (=ppm) * min) , derived by multiplying the ozone
      gas concentration during ozone gas sterilization by the sterilization time, was
      equal to or greater than the target value of 24 * 10(3) (ppm.min) . When the
      results of sterilization in a cleanroom were confirmed using a biological
      indicator (BI) , negative results were obtained at all measurement points,
      demonstrating that sterilization was being performed effectively in the actual
      factory at which the ozone gas sterilization system had been introduced.

PMID- 23538848
TI  - Stabilization of astaxanthin by a novel biosurfactant produced by Rhodotorula
      mucilaginosa KUGPP-1.
AB  - We found that a novel biosurfactant from the cultured broth of red yeast,
      Rhodotorula mucilaginosa KUGPP-1, originating in the Antarctic, has dispersive
      power against astaxanthin. The novel biosurfactant was purified from extracts to
      the ultrafiltration state by acetone precipitation and chromatography on a DEAE
      Toyopearl 650 M, and gel filtration on a Sephacryl S-400 HR. The molecular mass
      of the novel biosurfactant was estimated to be about 730,000 by gel filtration
      chromatography. The novel biosurfactant was comprised of sugar and protein in an
      approximate molar ratio of 9 : 1. The sugars were comprised of mannose, galactose
      and glucose. The particle size of the astaxanthin (0.13 u g/ml) micelle was about
      410 nm. Astaxanthin was stable to oxidation in the novel biosurfactant micelles.
      To our knowledge, this is the first report on a glycoprotein type of
      biosurfactant with astaxanthin-stabilizing ability.

PMID- 23538849
TI  - Characterization of the bacterial community in the sediment of a brackish lake
      with oyster aquaculture.
AB  - The physicochemical properties and bacterial community in sediments of Lake
      Shiraishi, a lake with brackish water, were characterized to elucidate the
      influence of oyster farming and seawater and freshwater inflow. Physicochemical
      analyses suggested the marine origin of the sediment at the mouth of the lake,
      while higher organic matter load and the resultant anaerobic, reductive condition
      of the sediments of the inner part were observed. The bacterial community in the
      sediments reflects these sediment environments: the bacterial community in the
      vicinities of oyster farms included sulfate-reducing bacteria (SRB) , although
      sulfur-oxidizing bacteria (SOB) were found at all the sampling sites. In
      addition, similarity of the band profiles obtained with 16S ribosomal RNA gene
      (16S rDNA) -denaturing gradient gel electrophoresis (DGGE) decreased in
      proportion to the distance from the mouth of the lake to the oyster farms in the
      inner part. This study was able to characterize the microbial community shift in
      brackish lake sediments with an oyster aquaculture system through the molecular
      fingerprinting technique, DGGE, in relation to their physicochemical
      characteristics.

PMID- 23538850
TI  - Effect of magnesium peroxide biostimulation of fish feed-loaded marine sediments
      on changes in the bacterial community.
AB  - The effect of an oxygen-releasing compound (ORC) magnesium peroxide (MgO(2)) on
      the changes in the bacterial community in organically polluted sediment of
      aquaculture farms was tested in a microcosm experiment. The sediment, to which
      fish feed was added, was treated with 1% or 5% MgO(2). The addition of fish feed
      induced a highly reduced environment with low redox potential, high total
      sulfides, and abundance of sulfate-reducing bacteria (SRB) . Although the
      sediment remained highly reduced at 1% MgO(2), there was a significant reduction
      of total sulfides, increase of redox potential, and resultant reduction of SRB.
      The bacterial community clearly changed with the treatments according to
      denaturing gradient gel electrophoresis (DGGE) analysis of 16S ribosomal RNA gene
      (16S rDNA) . Aerobes disappeared in the fish feed-added sediment, and some SRB
      emerged in place of these aerobes. On the other hand, the SRB disappeared in the
      ORC-amended sediment due to its highly oxic condition. This study revealed the
      bacterial community in the sediments was affected mainly by the redox potential
      and resultant sulfides produced by SRB, but total organic carbon and nitrogen
      were not determinants of the microbial population.

PMID- 23538851
TI  - Ecological study of pathogenic vibrios in aquatic environments.
AB  - An ecological study of pathogenic vibrios in aquatic environments of Okayama was
      carried out. The number of Vibrio parahaemolyticus detected in the sea area was
      comparatively smaler than that found in the survey of about two decades ago.
      Various reasons for the decrease in the case of food poisoning by V.
      parahaemolyticus have been suggested but the lower number of the vibrio in
      aquatic environments may be one explanation. Although the number of V. vulnificus
      was also not as large, most of the isolates possessed the pathogenic genes, vvp
      and vvh, suggesting the potential for fatal pathogenicity to patients having
      underlying diseases. As for V. cholerae, some non-O1/non-O139 serovar isolates
      were detected in a fresh water area, and many of them had hlyA, the gene for
      hemolysin which acts as a pathogenic factor in sporadic cases of diarrhea. Thus,
      the total number of pathogenic vibrios detected was not of concern. However, the
      marine products of these areas are shipped in wide area and are for general
      consumption. Therefore, it is necessary to continue to survey pathogenic vibrios
      in aquatic environments in order to ensure food hygiene.

PMID- 23538852
TI  - How to draw the line in biomedical research.
AB  - The use of the least squares method to calculate the best-fitting line through a
      two-dimensional scatter plot typically requires the user to assume that one of
      the variables depends on the other. However, in many cases the relationship
      between the two variables is more complex, and it is not valid to say that one
      variable is independent and the other is dependent. When analysing such data
      researchers should consider plotting the three regression lines that can be
      calculated for any two-dimensional scatter plot.

PMID- 23538853
TI  - Response to Roblin and Del Tedesco.

PMID- 23538854
TI  - [The development of TORS in Europe].
AB  - Transoral robotic surgery (TORS) using the da Vinci(r) System is being performed
      increasingly on an international level. Particularly in the US, TORS is a common
      and popular technique. It has several advantages over the alternative minimally
      invasive surgical technique of laser surgery: the 3D-HD lens generates a
      magnified, three dimensional deep-field view of the surgical site; the instrument
      has an exceptionally high degree of freedom and, in contrast to laser surgery,
      non-tangential incisions are possible. TORS is also being performed more
      frequently in Germany. At present, 10 TORS proctor surgeons with approval from
      Intuitive Surgical, Inc. are working in France, Belgium, Great Britain, Italy and
      Germany and helping to establish new TORS teams. This review article presents a
      summary of the literature that has been published by these European TORS experts
      to date.

PMID- 23538855
TI  - Cumulative total effective whole-body radiation dose in critically ill patients.
AB  - BACKGROUND: Uncertainty exists about a safe dose limit to minimize radiation
      induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years
      with no more than 50 mSv in any single year. Radiation exposure to the general
      population is less, but the average dose in the United States has doubled in the
      past 30 years, largely from medical radiation exposure. We hypothesized that
      patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and
      that trauma patients were more likely to exceed 50 mSv because of frequent
      diagnostic imaging. METHODS: Patients admitted into 15 predesignated SICU beds in
      a level I trauma center during a 30-day consecutive period were prospectively
      observed. Effective dose was determined using Huda's method for all radiography,
      CT imaging, and fluoroscopic examinations. Univariate and multivariable linear
      regressions were used to analyze the relationships between observed values and
      outcomes. RESULTS: Five of 74 patients (6.8%) exceeded exposures of 50 mSv.
      Univariate analysis showed trauma designation, length of stay, number of CT
      scans, fluoroscopy minutes, and number of general radiographs were all associated
      with increased doses, leading to exceeding occupational exposure limits. In a
      multivariable analysis, only the number of CT scans and fluoroscopy minutes
      remained significantly associated with increased whole-body radiation dose.
      CONCLUSIONS: Radiation levels frequently exceeded occupational exposure
      standards. CT imaging contributed the most exposure. Health-care providers must
      practice efficient stewardship of radiologic imaging in all critically ill and
      injured patients. Diagnostic benefit must always be weighed against the risk of
      cumulative radiation dose.

PMID- 23538856
TI  - Nonlinear estimation-based dipole source localization for artificial lateral line
      systems.
AB  - As a flow-sensing organ, the lateral line system plays an important role in
      various behaviors of fish. An engineering equivalent of a biological lateral line
      is of great interest to the navigation and control of underwater robots and
      vehicles. A vibrating sphere, also known as a dipole source, can emulate the
      rhythmic movement of fins and body appendages, and has been widely used as a
      stimulus in the study of biological lateral lines. Dipole source localization has
      also become a benchmark problem in the development of artificial lateral lines.
      In this paper we present two novel iterative schemes, referred to as Gauss-Newton
      (GN) and Newton-Raphson (NR) algorithms, for simultaneously localizing a dipole
      source and estimating its vibration amplitude and orientation, based on the
      analytical model for a dipole-generated flow field. The performance of the GN and
      NR methods is first confirmed with simulation results and the Cramer-Rao bound
      (CRB) analysis. Experiments are further conducted on an artificial lateral line
      prototype, consisting of six millimeter-scale ionic polymer-metal composite
      sensors with intra-sensor spacing optimized with CRB analysis. Consistent with
      simulation results, the experimental results show that both GN and NR schemes are
      able to simultaneously estimate the source location, vibration amplitude and
      orientation with comparable precision. Specifically, the maximum localization
      error is less than 5% of the body length (BL) when the source is within the
      distance of one BL. Experimental results have also shown that the proposed
      schemes are superior to the beamforming method, one of the most competitive
      approaches reported in literature, in terms of accuracy and computational
      efficiency.

PMID- 23538857
TI  - Oncogenic MUC1-C promotes tamoxifen resistance in human breast cancer.
AB  - Tamoxifen resistance of estrogen receptor-positive (ER+) breast cancer cells has
      been linked in part to activation of receptor tyrosine kinases, such as HER2, and
      the PI3K-AKT pathway. Mucin 1 (MUC1) is aberrantly overexpressed in about 90% of
      human breast cancers, and the oncogenic MUC1-C subunit is associated with
      ERalpha. The present studies using HER2 overexpressing BT-474 breast cancer
      cells, which are constitutively resistant to tamoxifen, demonstrate that
      silencing MUC1-C is associated with (i) downregulation of p-HER2 and (ii)
      sensitivity to tamoxifen-induced growth inhibition and loss of clonogenic
      survival. In contrast, overexpression of MUC1-C in tamoxifen-sensitive MCF-7
      breast cancer cells resulted in upregulation of p-AKT and tamoxifen resistance.
      We show that MUC1-C forms complexes with ERalpha on the estrogen-responsive
      promoter of Rab31 and that MUC1-C blocks tamoxifen-induced decreases in ERalpha
      occupancy. MUC1-C also attenuated tamoxifen-induced decreases in (i) recruitment
      of the coactivator CREB binding protein, (ii) Rab31 promoter activation, and
      (iii) Rab31 mRNA and protein levels. The importance of MUC1-C is further
      supported by the demonstration that targeting MUC1-C with the cell-penetrating
      peptide inhibitor, GO-203, sensitized tamoxifen-resistant cells to tamoxifen
      treatment. Moreover, we show that targeting MUC1-C in combination with tamoxifen
      is highly synergistic in the treatment of tamoxifen-resistant breast cancer
      cells. Combined, these findings indicate that MUC1-C contributes to tamoxifen
      resistance.

PMID- 23538859
TI  - Two novel 2D lanthanide-cadmium heterometal-organic frameworks based on nanosized
      heart-like Ln6Cd6O12 wheel-clusters exhibiting luminescence sensing to the
      polarization and concentration of cations.
AB  - Two novel 2D Ln-Cd HMOFs [Ln2Cd3(EDTA)3(H2O)11](H2O)14 (Ln = Sm 1; Eu 2; H4EDTA =
      ethylene diamine tetraacetic acid) based on nanosized heart-like Ln6Cd6O12 wheel
      clusters were hydrothermally synthesized and characterized. The luminescence
      sensing of 2 to the polarization and concentration of cations was discussed.

PMID- 23538858
TI  - ERK and AKT signaling drive MED1 overexpression in prostate cancer in association
      with elevated proliferation and tumorigenicity.
AB  - MED1 is a key coactivator of the androgen receptor (AR) and other signal
      activated transcription factors. Whereas MED1 is overexpressed in prostate cancer
      cell lines and is thought to coactivate distinct target genes involved in cell
      cycle progression and castration-resistant growth, the underlying mechanisms by
      which MED1 becomes overexpressed and its oncogenic role in clinical prostate
      cancer have remained unclear. Here, we report that MED1 is overexpressed in the
      epithelium of clinically localized human prostate cancer patients, which
      correlated with elevated cellular proliferation. In a Nkx3.1:Pten mutant mouse
      model of prostate cancer that recapitulates the human disease, MED1 protein
      levels were markedly elevated in the epithelium of both invasive and castration
      resistant adenocarcinoma prostate tissues. Mechanistic evidence showed that
      hyperactivated ERK and/or AKT signaling pathways promoted MED1 overexpression in
      prostate cancer cells. Notably, ectopic MED1 overexpression in prostate cancer
      xenografts significantly promoted tumor growth in nude mice. Furthermore, MED1
      expression in prostate cancer cells promoted the expression of a number of novel
      genes involved in inflammation, cell proliferation, and survival. Together, these
      findings suggest that elevated MED1 is a critical molecular event associated with
      prostate oncogenesis.

PMID- 23538860
TI  - Synthesis of disulfides and diselenides by copper-catalyzed coupling reactions in
      water.
AB  - A simple and efficient protocol for copper-catalyzed coupling reactions between
      aryl halides and elemental sulfur or selenium has been developed. A variety of
      disulfides and diselenides can be obtained in moderate to excellent yields up to
      96%.

PMID- 23538862
TI  - Protein instability following transport or storage on dry ice.

PMID- 23538861
TI  - FISH-quant: automatic counting of transcripts in 3D FISH images.

PMID- 23538863
TI  - Drilling into big cancer-genome data.

PMID- 23538864
TI  - Reproducibility restored--on toward the human interactome.

PMID- 23538865
TI  - A revolution coming to a classic model organism.

PMID- 23538866
TI  - KRAS mutation as the biomarker of response to chemotherapy and EGFR-TKIs in
      patients with advanced non-small cell lung cancer: clues for its potential use in
      second-line therapy decision making.
AB  - OBJETIVE: In patients with non-small cell lung cancer (NSCLC), knowledge of the
      epidermal growth factor receptor (EGFR) mutation status is fundamental for
      selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs).
      Little information is available regarding the response and progression-free
      survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the
      presence or absence of KRAS mutation, particularly in patients without EGFR
      mutation. METHODS: From 2007 to 2010, 353 patients with NSCLC were treated with
      first-line CT, EGFR-TKIs were used in the second or third line of treatment.
      Tests were performed for EGFR and KRAS mutation and the results of the mutations
      were obtained 3 to 4 months after the start of the treatment. We analyzed
      clinical characteristics, mutation profile, response and PFS to CT and EGFR-TKIs,
      and overall survival. The protocol is registered with ClinicalTrials.gov, number
      NCT01023828. RESULTS: Presence of the wild-type (WT) KRAS was independently
      associated with increased response rate to first-line CT when compared with KRAS
      mutation (41.4% vs. 14.7%; P=0.001). The EGFR mutation (57.8% vs. 11.7%; P<0.001)
      and WT-KRAS (39.6% vs. 3.3%; P=0.001) were associated with the EGFR-TKIs
      response. PFS of patients with WT-EGFR and KRAS mutation treated with EGFR-TKIs
      was shorter when compared with patients with WT-EGFR and WT-KRAS (P<0.001).
      CONCLUSIONS: KRAS mutation status is a good biomarker for response to EGFR-TKIs
      in patients with NSCLC. KRAS mutational status could impact the decision to give
      CT or EGFR-TKIs as a second line of treatment to patients with NSCLC,
      particularly in patients with WT-EGFR.

PMID- 23538867
TI  - Astaxanthin suppresses MPP(+)-induced oxidative damage in PC12 cells through a
      Sp1/NR1 signaling pathway.
AB  - OBJECTIVE: To investigate astaxanthin (ATX) neuroprotection, and its mechanism,
      on a 1-methyl-4-phenyl-pyridine ion (MPP+)-induced cell model of Parkinson's
      disease. METHODS: Mature, differentiated PC12 cells treated with MPP+ were used
      as an in vitro cell model. The MTT assay was used to investigate cell viability
      after ATX treatment, and western blot analysis was used to observe Sp1 (activated
      transcription factor 1) and NR1 (NMDA receptor subunit 1) protein expression,
      real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence
      was used to determine the location of Sp1 and NR1 protein and the nuclear
      translocation of Sp1. RESULTS: PC12 cell viability was significantly reduced by
      MPP+ treatment. The expression of Sp1 and NR1 mRNA and protein were increased
      compared with the control (p < 0.01). Following co-treatment with ATX and MPP+,
      cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were
      decreased, compared with the MPP+ groups (p < 0.01). In addition, mithracycin A
      protected PC12 cells from oxidative stress caused by MPP+ by specifically
      inhibiting the expression of Sp1. Moreover, cell immunofluorescence revealed that
      ATX could suppress Sp1 nuclear transfer. CONCLUSION: ATX inhibited oxidative
      stress induced by MPP+ in PC12 cells, via the SP1/NR1 signaling pathway.

PMID- 23538868
TI  - Diketopiperazine derivatives from the marine-derived actinomycete Streptomyces
      sp. FXJ7.328.
AB  - Five new diketopiperazine derivatives, (3Z,6E)-1-N-methyl-3-benzylidene-6-(2S
      methyl-3-hydroxypropylidene)piperazine-2,5-dione (1), (3Z,6E)-1-N-methyl-3
      benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione (2), (3Z,6Z)-3
      (4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione (3), (3Z,6Z)-3-((1H
      imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione (4), and (3Z,6S)-3
      benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione (5), were isolated from the
      marine-derived actinomycete Streptomyces sp. FXJ7.328. The structures of 1-5 were
      determined by spectroscopic analysis, CD exciton chirality, the modified
      Mosher's, Marfey's and the C3 Marfey's methods. Compound 3 showed modest
      antivirus activity against influenza A (H1N1) virus with an IC50 value of 41.5 +/
      4.5 MUM. In addition, compound 6 and 7 displayed potent anti-H1N1 activity with
      IC50 value of 28.9 +/- 2.2 and 6.8 +/- 1.5 MUM, respectively. Due to the lack of
      corresponding data in the literature, the 13C NMR data of (3Z,6S)-3-benzylidene-6
      isobutylpiperazine-2,5-dione (6) were also reported here for the first time.

PMID- 23538869
TI  - (+/-)-Pestalachloride D, an antibacterial racemate of chlorinated benzophenone
      derivative from a soft coral-derived fungus Pestalotiopsis sp.
AB  - A new antibacterial chlorinated benzophenone derivative, (+/-)-pestalachloride D
      (1), along with a related analog, (+/-)-pestalachloride C (2), was recently
      isolated from the marine-derived fungus Pestalotiopsis sp. isolated from a soft
      coral Sarcophyton sp. collected from Yongxing Island in the South China Sea. Both
      chiral HPLC analysis and single-crystal X-ray data indicated that 1 is a racemic
      mixture. Interestingly, 1 did not exhibit any effect in the zebrafish embryo
      teratogenicity assay, while 2 led to abnormal growth. The potential impact on
      zebrafish embryo growth is discussed based on their crystal structures. The main
      difference of crystal structures between 1 and 2 is that the six-member non
      aromatic ring (O4, C10, C9, C8, C2', and C3') in 1 exhibits a distorted chair
      conformation, while 2 shows a distorted boat conformation. Moreover, compounds 1
      and 2 both exhibited moderate antibacterial activity.

PMID- 23538870
TI  - Bioactive compounds from the Red Sea marine sponge Hyrtios species.
AB  - In continuation of our search for drug leads from Red Sea sponges we have
      investigated the ethyl acetate fraction of the organic extract of the Red Sea
      sponge Hyrtios species. Bioassay-directed fractionation of the active fraction
      resulted into the identification of three new alkaloids, hyrtioerectines D-F (1
      3). Hyrtioerectines D-F belong to the rare marine alkaloids in which the indole
      and beta-carboline fragments of the molecule are linked through C-3/C-3 of both
      moieties. The structures of the isolated compounds were established based on
      different spectroscopic data including UV, IR, 1D and 2D NMR (COSY, HSQC, and
      HMBC) and high-resolution mass spectral studies. The antimicrobial activity
      against several pathogens and the free radical scavenging activity of the
      compounds using DPPH reagent were evaluated. In addition, the growth inhibitory
      activity of the compounds against three cancer cell lines was also evaluated.
      Hyrtioerectines D-F (1-3) displayed variable antimicrobial, free radical
      scavenging and cancer growth inhibition activities. Generally, compounds 1 and 3
      were more active than compound 2.

PMID- 23538871
TI  - Sponge-derived Kocuria and Micrococcus spp. as sources of the new thiazolyl
      peptide antibiotic kocurin.
AB  - Forty four marine actinomycetes of the family Microccocaceae isolated from
      sponges collected primarily in Florida Keys (USA) were selected from our strain
      collection to be studied as new sources for the production of bioactive natural
      products. A 16S rRNA gene based phylogenetic analysis showed that the strains are
      members of the genera Kocuria and Micrococcus. To assess their biosynthetic
      potential, the strains were PCR screened for the presence of secondary metabolite
      genes encoding nonribosomal synthetase (NRPS) and polyketide synthases (PKS). A
      small extract collection of 528 crude extracts generated from nutritional
      microfermentation arrays was tested for the production of bioactive secondary
      metabolites against clinically relevant strains (Bacillus subtilis, methicillin
      resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii and Candida
      albicans). Three independent isolates were shown to produce a new anti-MRSA
      bioactive compound that was identified as kocurin, a new member of the thiazolyl
      peptide family of antibiotics emphasizing the role of this family as a prolific
      resource for novel drugs.

PMID- 23538872
TI  - Mass spectrometric detection of multiple extended series of neutral highly
      fucosylated N-acetyllactosamine oligosaccharides in human milk.
AB  - Complex mixtures of high molecular weight fractions of pooled neutral human milk
      oligosaccharides (obtained via gel permeation chromatography) have been
      investigated. The subfractions were each permethylated and analyzed by high
      resolution mass spectrometry, using matrix-assisted laser desorption/ionization
      (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry, in
      order to investigate their oligosaccharide compositions. The obtained spectra
      reveal that human milk contains more complex neutral oligosaccharides than have
      been described previously; the data show that these oligosaccharides can be
      highly fucosylated, and that their poly-N-acetyllactosamine cores are substituted
      with up to 10 fucose residues on a an oligosaccharide that has 7-N
      acetyllactosamine units. This is the first report of the existence in human milk
      of this large range of highly fucosylated oligosaccharides which possess novel,
      potentially immunologically active structures.

PMID- 23538873
TI  - Hormonal interactions and gene regulation can link monoecy and environmental
      plasticity to the evolution of dioecy in plants.
AB  - Most models for dioecy in flowering plants assume that dioecy arises directly
      from hermaphroditism through a series of independent feminizing and masculinizing
      mutations that become chromosomally linked. However, dioecy appears to evolve
      most frequently through monoecious grades. The major genetic models do not
      explain the evolution of unisexual flowers in monoecious and submonoecious
      populations, nor do they account for environmentally induced sexual plasticity.
      In this review, we explore the roles of environmental stress and hormones on sex
      determination, and propose a model that can explain the evolution of dioecy
      through monoecy, and the mechanisms of environmental sex determination.
      Environmental stresses elicit hormones that allow plants to mediate the negative
      effects of the stresses. Many of these same hormones are involved in the
      regulation of floral developmental genes. Recent studies have elucidated the
      mechanisms whereby these hormones interact and can act as switchpoints in
      regulatory pathways. Consequently, differential concentrations of plant hormones
      can regulate whole developmental pathways, providing a mechanism for differential
      development within isogenic individuals such as seen in monoecious plants. Sex
      determining genes in such systems will evolve to generate clusters of coexpressed
      suites. Coexpression rather than coinheritance of gender-specific genes will
      define the sexual developmental fate. Therefore, selection for gender type will
      drive evolution of the regulatory sequences of such genes rather than their
      synteny. Subsequent mutations to hyper- or hyposensitive alleles within the
      hormone response pathway can result in segregating dioecious populations.
      Simultaneously, such developmental systems will remain sensitive to external
      stimuli that modify hormone responses.

PMID- 23538874
TI  - Phylogeography of North American herbaceous Smilax (Smilacaceae): Combined AFLP
      and cpDNA data support a northern refugium in the Driftless Area.
AB  - PREMISE OF THE STUDY: The genetic structure of North American herbaceous Smilax,
      a clade of closely related understory herbs that has a wide and disjunct
      distribution, was investigated to test the hypothesis of whether a northern
      refugium in the upper Midwest may have existed for these plants during the last
      glaciation. METHODS: We analyzed 33 populations sampled from California and
      throughout the eastern United States using AFLP and chloroplast DNA sequence
      data. KEY RESULTS: Individuals of S. jamesii from northern California formed a
      clade sister to the eastern North American species, and they likely diverged from
      each other during the Pleistocene. Among the eastern species, two lineages were
      found on opposite sides of the Appalachian Mountains. The populations near the
      "Driftless Area" contained most of the chlorotypes found in the Midwest,
      including a unique one endemic to this area, and the AFLP data indicated that one
      population from this area has the highest frequency-down-weighted-marker value.
      CONCLUSIONS: This study, and others that have focused on mammals, amphibians, and
      woody plants, provides further evidence for the debate over whether the upper
      Midwest's "Driftless Area" may have hosted a biologically diverse northern
      glacial refugium. Herbaceous species of Smilax from eastern North American
      exhibit an Appalachian discontinuity. They appear to have persisted in multiple
      refugia both east and west of the Appalachians, with several populations
      persisting in situ through the Last Glacial Maximum (LGM). We suggest that they
      experienced localized expansion after the LGM, possibly followed by subsequent
      contact between the Midwest and the East Coastal lineages.

PMID- 23538875
TI  - Symptoms and risk factors for stroke in a community-based observational sample in
      Viet Nam.
AB  - BACKGROUND: Viet Nam is experiencing a health transition from infectious to
      chronic disease. Data on cardiovascular diseases, including strokes, are limited.
      METHODS: Data were randomly collected from six communities in Da Nang, Viet Nam,
      on participant demographics, medical history, blood pressure, anthropometrics and
      health behavior using World Health Organization (WHO) guidelines. Stroke symptoms
      were collected by self-report with the standardized Questionnaire for Verifying
      Stroke Free Status. Multivariate logistic regression was used to identify factors
      associated with the presence of stroke symptoms. RESULTS: One thousand six
      hundred and twenty one adults were examined with a mean age of 52.0 years (+/-
      12.5 years), of which 56.1% were women. 27.3% of the participants were found to
      have hypertension, 26.2% used tobacco, and 16.1% were overweight. More than two
      thirds of the participants with hypertension were unaware of their condition.
      Almost one fourth of the participants were identified by the questionnaire as
      previously experiencing at least one stroke symptom. Age, rural residence, and
      education were associated with the presence of stroke symptoms. Models adjusted
      for demographics found hypertension, high cholesterol, reported severe chest
      pain, former smoking, and being overweight to be associated with a higher
      prevalence of stroke symptoms. CONCLUSIONS: The high frequency of stroke symptoms
      in Da Nang calls for further evaluation and interventions to reduce hypertension
      and other risk factors for chronic disease in Viet Nam and other health
      transition countries.

PMID- 23538876
TI  - Influence of percutaneous local therapy for hepatocellular carcinoma on gastric
      function.
AB  - AIM: To investigate the influence of percutaneous local therapy on gastric
      myoelectrical activity in patients with hepatocellular carcinomas. METHODS: Forty
      four patients with hepatocellular carcinoma (HCC) [27 males and 17 females,
      ranging in age from 49 to 81 years old (69.7 +/- 8.01 years)] who were admitted
      for percutaneous local therapy were enrolled in this study. We examined clinical
      abdominal symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) before
      and 3 d after percutaneous local therapy. We also measured cutaneous fasting and
      postprandial electrogastrography (EGG) recordings before and 3 d after
      percutaneous local therapy. RESULTS: We found that the percentage of normogastria
      in the fasting period was lower in the Child B group than in the Child A group
      (66.8% +/- 8.6% vs 84.0% +/- 3.8%). After percutaneous local therapy for HCC, the
      percentages of normogastria in the fasting period were significantly decreased
      (81.6% +/- 3.5% vs 75.2% +/- 4.5%). None of the postprandial EGG parameters
      changed significantly after percutaneous local therapy for HCC. Percutaneous
      local therapy for HCC reduced the power ratio (PR). In particular, the PR of
      tachygastria was significantly decreased after therapy (P < 0.01). However, no
      significant differences were found in the postprandial EGG parameters. Likewise,
      no significant differences were found in the calculated GSRS scores obtained from
      the questionnaire before and after therapy. CONCLUSION: Gastric slow-wave
      dysrhythmias were induced by percutaneous local therapy in HCC patients, even
      though the GSRS scores obtained from the questionnaire did not change
      significantly.

PMID- 23538877
TI  - Approaches to the Management of Acute Kidney Injury in Children.
AB  - Acute kidney injury (AKI) causes increased morbidity in critically ill children
      and damage to the kidney, a central mediator of homeostasis in the body, affects
      survival. The incidence of AKI in pediatrics is significant and despite alarming
      data, therapeutic interventions have failed to effect a meaningful difference in
      outcomes. In this review, we will discuss the epidemiology of AKI in pediatrics,
      treatment strategies attempted to date, experimental therapies targeting
      molecular patterns associated with AKI, and highlight the needed direction of AKI
      research and management. Prospective trials in pediatrics are needed to test the
      validity of diagnostic tools, to identify the point of most efficacious
      intervention, and to underscore the therapies that can be effective in the
      different downstream effects of AKI.

PMID- 23538878
TI  - What's new is older.
AB  - Distinct populations of active cells in the dentate gyrus of the hippocampus may
      facilitate the unique encoding of changes in the environment.

PMID- 23538879
TI  - Chiral recognition of amino acid esters by a novel oxalic amide-linked
      bisporphyrin.
AB  - A novel oxalic amide-linked bisporphyrinate 1has been designed and synthesized,
      which shows chiral recognition ability for amino acid ethyl esters. The structure
      of complex 1.(D-Phe-OEt)(L-Phe-OEt) has been solved by X-ray crystallography. It
      reveals the following information: bisporphyrin unit adopts anti-configuration;
      compound 1forms 1: 2 complex with amino acid ethyl esters; one important hydrogen
      bond is formed between the coordinated nitrogen of amino acid ester and carbonyl
      oxygen in the amide group. The chiral recognition mechanism has been further
      investigated by UV-Vis spectra, (1)H NMR and DFT/TDDFT calculations.

PMID- 23538880
TI  - The Evolution of Fruit Tree Productivity: A Review.
AB  - The Evolution of Fruit Tree Productivity: A Review. Domestication of fruit trees
      has received far less attention than that of annual crop plants. In particular,
      very little is known about the evolution of fruit tree productivity. In the wild,
      most tree species reach reproductive maturity after a long period of juvenility
      and even then, sexual reproduction appears sporadically, often in a mode of
      masting. Environmental constraints limit trees' reproductive activity in their
      natural, wild habitats, resulting in poor, irregular productivity. Early
      fructification and regular, high rates of productivity have been selected by
      people, unconsciously and consciously. The reviewed evidence indicates an
      evolutionary continuum of productivity patterns among trees of wild habitats,
      intermediary domesticates, and the most advanced domesticates. Alternate bearing
      appears to represent an intermediate step in the fruit tree evolutionary pathway.
      The existence of a molecular, genetic mechanism that controls trees' sexual
      reproduction and fruiting pattern is suggested.

PMID- 23538881
TI  - Cathepsin D: Autoantibody profiling as a diagnostic marker for cancers.
AB  - Current diagnostic assays for many cancers are antigen-based and rely on the
      detection of circulating proteins that are associated with a particular cancer.
      These assays depend on the expression, synthesis, and release of specific
      proteins by cells (e.g., tumor cells) through either active secretion or
      shedding, or as a consequence of cell death (either necrosis or apoptosis). As
      such, these antigenic proteins must "escape" the primary site of disease,
      saturate the antigen-processing capacity of the individual's immune components,
      gain access to the circulation, and reach a sufficient steady-state concentration
      to be detected by enzyme- or radiolabel-based immunoassays. These events usually
      occur after the initial establishment of disease. Thus, and despite the fact that
      certain specific antigenic epitopes exhibit common recognition among patients
      with the same tumor types, the use of these antigen-based cancer assays has not
      been widely accepted in clinical practice, and many individual countries differ
      in the use of these potential diagnostic factors. Lately, an increasing number of
      studies demonstrated that procathepsin D secreted from cancer cells, acts as a
      mitogen on cancer cells and stimulates their pro-invasive and pro-metastatic
      properties. In this report, we focused on the possibility to use anti
      procathepsin D autoantibodies as a diagnostic and/or predictive marker for
      cancers.

PMID- 23538882
TI  - Qualitative and quantitative metabolomic investigation of single neurons by
      capillary electrophoresis electrospray ionization mass spectrometry.
AB  - Single-cell mass spectrometry (MS) empowers metabolomic investigations by
      decreasing analytical dimensions to the size of individual cells and subcellular
      structures. We describe a protocol for investigating and quantifying metabolites
      in individual isolated neurons using single-cell capillary electrophoresis (CE)
      coupled to electrospray ionization (ESI) time-of-flight (TOF) MS. The protocol
      requires ~2 h for sample preparation, neuron isolation and metabolite extraction,
      and 1 h for metabolic measurement. We used the approach to detect more than 300
      distinct compounds in the mass range of typical metabolites in various individual
      neurons (25-500 MUm in diameter) isolated from the sea slug (Aplysia californica)
      central and rat (Rattus norvegicus) peripheral nervous systems. We found that a
      subset of identified compounds was sufficient to reveal metabolic differences
      among freshly isolated neurons of different types and changes in the metabolite
      profiles of cultured neurons. The protocol can be applied to the characterization
      of the metabolome in a variety of smaller cells and/or subcellular domains.

PMID- 23538883
TI  - Isolation and in vitro culture of primary cardiomyocytes from adult zebrafish
      hearts.
AB  - This protocol describes how to isolate primary cardiomyocytes from adult
      zebrafish hearts and culture them for up to 4 weeks, thereby using them as an
      alternative to in vivo experiments. After collagenase digestion of the ventricle,
      cells are exposed to increasing calcium concentrations in order to obtain high
      purity cardiomyocytes. The whole isolation process can be accomplished in 4-5 h.
      The culture conditions we established allow the cells to preserve their mature
      sarcomeric integrity and contractile properties. Furthermore, adult zebrafish
      cardiomyocytes in culture, similarly to zebrafish in vivo heart regeneration,
      undergo partial dedifferentiation and, in contrast to their mammalian
      counterparts, are able to proliferate. Our protocol enables the study of
      structural and functional properties in close-to-native cardiomyocytes and allows
      the application of in vitro techniques and assays that are not feasible to
      perform in living animals.

PMID- 23538885
TI  - Impact of clinical and lesion characteristics on the results of MR-guided wire
      localizations of the breast using an open 1.0-T MRI system.
AB  - PURPOSE: Preoperative magnetic resonance (MR)-guided wire localizations are
      warranted in patients with suspicious focal breast lesions on MR mammographic
      findings without equivalent in x-ray mammography and ultrasonography. The study
      was performed to assess the impact of clinical parameters, tumor size, and target
      localization on the procedural characteristics in magnetic resonance imaging
      (MRI)-guided wire localizations of breast lesions using an open 1.0-T open MR
      system. MATERIAL AND METHODS: The clinical, radiological, and histological
      characteristics of all 347 patients and all 394 interventional procedures
      performed in a 6-year interval were extracted from the clinical files. Two board
      certified senior radiologists evaluated the impact of target localization and the
      size on the interventional results in the available 302 image data sets. Patient
      characteristics, lesion characteristics, and interventional results were
      statistically correlated in subgroup analyses. RESULTS: A total of 387 of the 394
      MR-guided wire localizations (98.2%) were technically successful. In 7 cases
      (2.3%), the intervention was aborted because the suspicious finding of the
      diagnostic MR mammography could not be visualized during the intervention. Minor
      complications occurred in 13 interventions (3.3%). The histological workup of the
      operative specimen showed benign results in 226 of the 394 interventions (57.4%)
      and malignant findings in 154 wire localizations (39.1%). The mean (SD) length of
      the interventional procedure time defined as the time interval between the start
      of the first and of the last MRI sequence as documented in the electronic MRI
      data sets was 24.6 (8.4) minutes. Patient age, medical history, and the
      anticipated risk for developing breast cancer and a simultaneous known carcinoma
      did not affect the technical success and complication rates and the
      interventional procedure time. A total of 60 targets (19.5%) were located in the
      retromamillary zone, 89 targets (28.9%) in the peripheral zone, and 1 target
      (0.3%) near the chest wall. The maximum diameter was 1 to 5 mm in 64 lesions
      (21.2%), 6 to 10 mm in 136 lesions (45.0%), 11 to 15 mm in 56 lesions (18.6%),
      and 16 mm or greater in 46 lesions (15.2%). A total of 23 of the 100
      histologically proven invasive carcinomas had a maximum MRI diameter of 1 to 5 mm
      (23.0%) and 38 (38.0%) of 6 to 10 mm. CONCLUSIONS: Magnetic resonance-guided wire
      localizations of suspicious breast lesions using an open high-field MR system are
      a clinically safe and feasible method even in small target lesions and anatomical
      regions that are usually considered difficult to access.

PMID- 23538886
TI  - CAIPIRINHA-Dixon-TWIST (CDT)-volume-interpolated breath-hold examination (VIBE):
      a new technique for fast time-resolved dynamic 3-dimensional imaging of the
      abdomen with high spatial resolution.
AB  - PURPOSE: The purpose of this study was to assess the feasibility and image
      quality of a novel, highly accelerated T1-weighted sequence for time-resolved
      imaging of the abdomen during the first pass of contrast media transit using
      controlled aliasing in parallel imaging results in higher acceleration
      (CAIPIRINHA) under sampling, view-sharing techniques, and Dixon water-fat
      separation (CAIPRINHA-Dixon-time-resolved imaging with interleaved stochastic
      trajectories-volumetric interpolated breath-hold examination [CDT-VIBE]).
      MATERIALS AND METHODS: In this retrospective, institutional review board-approved
      study, 47 patients (median age, 62 years; 25 men, 22 women) scanned on a 3.0-T
      magnetic resonance system (Skyra; Siemens) were included. The CDT-VIBE
      (repetition time/echo time1/echo time2, 4.1/1.33/2.56 milliseconds; acquisition
      time, 29 seconds) was used in place of the standard arterial phase acquisition
      and started 15 seconds after the injection of 0.1 mmol/kg Gd-DOTA (Dotarem,
      Guerbet). Within 29 seconds, 14 high spatial resolution (1.2 * 1.2 * 3 mm) 3
      dimensional data sets were acquired and reconstructed using view sharing
      (temporal resolution, 2.1 seconds). The CDT-VIBE images were evaluated
      independently by 2 blinded, experienced radiologists with regard to image quality
      and the number of hepatic arterial-dominant phases present on an ordinal 5-point
      scale (5, excellent; 1, nondiagnostic). Added diagnostic information with CDT
      VIBE relative to portal venous phase VIBE was assessed. RESULTS: In all patients,
      CDT-VIBE measurements were successfully acquired. The image quality was
      diagnostic in 46 of the 47 patients. Both readers assessed the highest image
      quality present in the data sets with a median score of 4 (range, 3-5 for both
      readers; kappa, 0.789) and the worst image quality with a median score of 3
      (range, 1-4 for both readers; kappa, 0.689). With a range between 1 and 8
      (median, 5), hepatic arterial-dominant data sets (of the 14 acquired) were
      obtained in each case. There was an added diagnostic value with CDT-VIBE in 10 of
      the 47 patients (21%). CONCLUSIONS: The CDT-VIBE is a robust approach allowing,
      for the first time, dynamic imaging of the upper abdomen with high temporal
      resolution and preservation of high spatial resolution.

PMID- 23538887
TI  - Prediction of postoperative lung function in patients undergoing lung resection:
      dual-energy perfusion computed tomography versus perfusion scintigraphy.
AB  - OBJECTIVES: The purpose of this study was to assess the usefulness of dual-energy
      perfusion computed tomography (CT) for predicting postoperative lung function in
      patients undergoing lung resection. METHODS: Fifty-one patients (38 men, 13
      women; mean age, 63.8 years) were prospectively enrolled and subsequently
      underwent dual-energy CT, perfusion scintigraphy, a pulmonary function test
      before surgery, and a pulmonary function test 6 months after surgery. Computed
      tomography was performed using dual-source CT with the dual-energy technique.
      Using weighted average images, each lobe was segmented and using perfusion
      images, the iodine value was quantitatively measured. Lobar perfusion was
      calculated by multiplying the volume of the lobe by the iodine value. The ratio
      of lobar perfusion per whole-lung perfusion was then calculated. The predicted
      postoperative forced expiratory volume during 1 second (post-FEV1) was calculated
      by multiplying the preoperative FEV1 by the fractional contribution of perfusion
      of the remaining lung. The agreement between the predicted post-FEV1 and the
      actual post-FEV1 was then evaluated. The percentage of error of the predicted
      post-FEV1 to that of the actual post-FEV1 was then calculated. RESULTS: Using the
      Bland-Altman method, the limits of agreement between the actual post-FEV1 and the
      predicted post-FEV1 were -29.3% and 26.9% for scintigraphy and -28.9% and 17.3%
      for CT. The percentage of error of CT (15.4%) was comparable with that of
      scintigraphy (17.8%). CONCLUSIONS: Dual-energy perfusion CT was more accurate
      than perfusion scintigraphy was for predicting postoperative lung function.

PMID- 23538888
TI  - In vitro high-resolution flat-panel computed tomographic arthrography for
      artificial cartilage defect detection: comparison with multidetector computed
      tomography.
AB  - OBJECTIVES: The objectives of this study were to analyze the spatial resolution
      of different reconstruction kernels and acquisition protocols, including a
      prototypic high-resolution protocol in flat-panel (FP) and multidetector (MD)
      computed tomography (CT), and to evaluate contrast and artificial cartilage
      depiction quality of in vitro FPCT and MDCT arthrography. MATERIALS AND METHODS:
      An image-quality cone beam phantom was used to compare resolution and different
      reconstruction kernels of the standard MDCT (120 and 80 kV) and the standard
      binned (2 * 2) and prototypic high-resolution unbinned (1 * 1) FPCT protocols (5-
      and 20-second runs each). With the resulting FPCT kernel best matching the
      standard MDCT kernel (U90u), artificial joint phantoms with differently sized
      groups of cartilage defects (2, 1, 0.5, and 0.3 mm in width) were then scanned
      using intra-articular iodinated contrast at 50 mgI/mL. In these joint phantoms,
      CT numbers and noise in the iodinated contrast and artificial cartilage tissue
      were measured and contrast-to-noise ratios (CNR) were calculated. Depiction
      quality of artificial cartilage defects was qualitatively rated by 2 independent
      radiologists. RESULTS: A sharp reconstruction kernel for all FPCT protocols
      suited best for matched resolution to the standard MDCT kernel. High-resolution
      20-second 1 * 1 binning FPCT showed comparable resolution with MDCT in the range
      of 0.4 to 1.6 line pairs (lp) per millimeter with superior resolution in higher
      frequencies than 1.6 lp per millimeter (P < 0.001). Flat-panel computed
      tomographic 5-second runs were associated with higher image noise than the 20
      second runs were. The CNR differed significantly among the protocols (P < 0.01)
      and was the highest in the 20-second FPCT, followed by the 5-second FPCT 2 * 2
      and MDCT protocols. Interreader agreement for the depiction quality of artificial
      cartilage defects was substantial and high in the joint phantoms (0.74 and 0.81,
      respectively; P < 0.001). The best ratings of the artificial cartilage defect
      depiction quality were seen in the FPCT 20-second, followed by the FPCT 5-second
      and MDCT acquisitions. The depiction quality of smaller cartilage defects (1.0
      and 1.67 lp per millimeter) was rated worst in the MDCT acquisitions.
      CONCLUSIONS: In vitro FPCT arthrography offers superior CNR and artificial
      cartilage defect depiction quality to MDCT, and spatial resolution for small
      structures is higher when applying high-resolution acquisition protocols. Flat
      panel computed tomography, thus, has the potential to improve workflow, and
      tailored high-resolution protocols may allow for advanced cartilage evaluation in
      CT arthrography.

PMID- 23538889
TI  - Comparison of magnetic resonance elastography and gadoxetate disodium-enhanced
      magnetic resonance imaging for the evaluation of hepatic fibrosis.
AB  - OBJECTIVES: The objective of this study was to compare the diagnostic performance
      of magnetic resonance elastography (MRE) and gadoxetate disodium-enhanced
      magnetic resonance imaging (MRI) in the staging of hepatic fibrosis (HF) in
      patients with liver diseases. MATERIALS AND METHODS: This retrospective study was
      approved by our institutional review board, and the informed consent was waived.
      One hundred and sixty-eight patients with chronic liver disease or suspected
      focal hepatic lesions underwent MRE and gadoxetate disodium-enhanced MRI at 1.5
      T. Liver stiffness values were measured on quantitative shear-stiffness maps. The
      contrast enhancement index (CEI) was calculated as SIpost / SIpre, where SIpost
      and SIpre are, respectively, the liver-to-muscle signal intensity (SI) ratio on
      hepatobiliary phase images and on unenhanced images. The diagnostic performance
      of MRE and CEI for staging HF was compared using the receiver operating
      characteristic curve analysis on the basis of the histopathologic analysis of HF.
      RESULTS: The liver stiffness values measured on MRE (r = 0.802; P < 0.0001) were
      more strongly correlated with the HF stage than with the CEI (r = -0.378; P <
      0.0001). The areas under the receiver operating characteristic curve values of
      the liver stiffness values were significantly larger than those of CEI were for
      discriminating all stages of HF (P < 0.001 for >= F1, >= F2, >= F3, and >= F4).
      Magnetic resonance elastography showed higher sensitivity and specificity for
      predicting HF >= F1 (91% and 87%), >= F2 (87% and 91%), >= F3 (80% and 89%), and
      F4 (81% and 85%) compared with CEI (46% and 85%, 46% and 82%, 63% and 68%, and
      76% and 65%, respectively). CONCLUSIONS: Magnetic resonance elastography was
      superior to the gadoxetate disodium-enhancement MRI for HF staging.

PMID- 23538890
TI  - Clinical image quality assessment of accelerated magnetic resonance neuroimaging
      using compressed sensing.
AB  - PURPOSE: The aim of this study was to determine to what degree current compressed
      sensing methods are capable of accelerating clinical magnetic resonance
      neuroimaging sequences. METHODS: Two 2-dimensional clinical sequences were chosen
      for this study because of their long scan times. A pilot study was used to
      establish the sampling scheme and regularization parameter needed in compressed
      sensing reconstruction. These findings were used in a subsequent blinded study in
      which images reconstructed using compressed sensing were evaluated by 2 board
      certified neuroradiologists. Image quality was evaluated at up to 10 anatomical
      features. RESULTS: The findings indicate that compressed sensing may provide 2
      fold acceleration of certain clinical magnetic resonance neuroimaging sequences.
      A global ringing artifact and image blurring were identified as the 2 primary
      artifacts that would hinder the ability to confidently discern abnormality.
      CONCLUSION: Compressed sensing is able to moderately accelerate certain
      neuroimaging sequences without severe loss of clinically relevant information.
      For those sequences with coarser spatial resolution and/or at a higher
      acceleration factor, artifacts degrade the quality of the reconstructed image to
      a point where they are of little to no clinical value.

PMID- 23538891
TI  - Terrestrial gamma radiation and its statistical relation with geological
      formation in the Mersing district, Johor, Malaysia.
AB  - An extensive survey was carried out for gamma dose rates (GDRs) in the Mersing
      district, Johor, Malaysia. The average value of GDR measured in the district was
      found to be 140 nGy h(-1), in the range of 40-355 nGy h(-1). The mean weighted
      dose rate to the population, annual effective dose equivalent, collective
      effective dose equivalent, lifetime cancer risk were 0.836 mSv y(-1), 0.171 mSv,
      1.18 * 10(1) man Sv y(-1) and 6.98 * 10(-4) Sv y, respectively. An isodose map
      was produced for the district. One way analysis of variance was used to test for
      differences due to different geological formations present in the Mersing
      District.

PMID- 23538892
TI  - Photoneutron contamination from an 18 MV Saturne medical linear accelerator in
      the treatment room.
AB  - Dose escalation with high-energy X rays of medical linear accelerators (linacs)
      in radiotherapy offers several distinct advantages over the lower energy photons.
      However, owing to photoneutron reactions, interaction of high-energy photons (>8
      MV) with various high-Z nuclei of the materials in the linac head components
      produces unavoidable neutrons. The aim of this study was to evaluate the
      photoneutron dose equivalent per unit therapeutic X-ray dose of 18 MV, GE Saturne
      20 linac in the treatment room using Monte Carlo (MC) MCNP linac head full
      simulation as well as thermoluminescence dosemeter measurements. This machine is
      one of the old linac models manufactured by General Electric Company; however, it
      is widely used in the developing countries because of low cost and simple
      maintenance for radiotherapy applications. The results showed a significant
      photoneutron dose from Saturne 20 linac head components especially at distances
      near the linac head (<150 cm). Results of this work could be used in several
      applications, especially designing bunker and entrance door shielding against
      neutrons produced by photoneutron reactions in GE Saturne 20. However, a detailed
      cost optimisation for a specific room would require a dedicated calculation. 

PMID- 23538894
TI  - The solvent effect and identification of a weakly emissive state in nonradiative
      dynamics of guanine nucleosides and nucleotides--a combined femtosecond broadband
      time-resolved fluorescence and transient absorption study.
AB  - A combined method of femtosecond broadband time-resolved fluorescence (fs-TRF)
      and transient absorption (fs-TA) was employed to investigate the excited state
      dynamics of 2'-deoxyguanosine (dG) and 2'-deoxyguanosine 5'-monophosphate (dGMP).
      Comparative fs-TRF and fs-TA measurements were conducted on dG and dGMP in
      neutral water, deuterated water, and methanol with excitation wavelengths of 245,
      267 and 285 nm. Very similar results were observed with dG and dGMP. The data
      provide compelling evidence for the co-existence of two nonradiative pathways.
      One is the generally recognized Lapipi* mediated channel, the other involves an
      unprecedented weakly emissive state which plays a significant role in the overall
      deactivation processes. The Lapipi* channel features biphasic dynamics with time
      constants (tau1/tau2) of ~0.2/0.8 ps in water and ~0.25/1.0 ps in methanol. The
      biphasic decay arises due to a partial transfer with tau1 of the Lapipi*
      population to the newly identified state followed by conversion in tau2 of the
      remaining Lapipi* molecules into the electronic ground state. The channel
      mediated by the weakly emissive species shows solvent-dependent dynamics with
      time constants (tau3) of ~2.0 ps in water, ~2.3 ps in deuterated water, and ~4.1
      ps in methanol. The species features absorption at UV wavelengths (~300-400 nm)
      and exhibits deeply red-shifted fluorescence (lambdamax ~ 520 nm) with
      polarization direction varied markedly from that of the Lapipi* but close to the
      Lbpipi*. This species acts as an effective quenching state to the radiative decay
      of the brightly emissive Lapipi* and Lbpipi*. It sets in promptly (<~50 fs) after
      the photoexcitation and is further populated through nonadiabatic coupling with
      the Lapipi*. The overall involvement of this state is facilitated with excitation
      at high energy and is favoured in methanol over water. According to the spectral
      character and the solvent effect in particular the kinetic isotope effect, the
      species is tentatively associated to the pisigma* state with charge transfer (CT)
      character which is considered to be preferentially stabilized by hydrogen-bonding
      between the guanine amino and surrounding solvent molecules. The result of this
      study leads to a dramatically different picture of guanine deactivation. It
      demonstrates a crucial role of the solvent in shaping the nonradiative dynamics
      of guanine nucleosides and nucleotides. The data presented are important for
      understanding the detailed photophysics of not only the monomeric guanine but
      also DNA assemblies that contain guanine in base pairs or have a guanine tetrad
      as the structural motif.

PMID- 23538893
TI  - Hepatic regeneration and the epithelial to mesenchymal transition.
AB  - Liver injuries are repaired by fibrosis and regeneration. The core stage is the
      repair response and fibrosis formation as a scar. The cause of overly-responsive
      scar formation and diminished regeneration, especially in liver fibrosis and
      cirrhosis, is still unknown. The epithelial to mesenchymal transition (EMT), a
      previously discovered mechanism, plays an important role in liver fibrosis and
      tumor metastasis. Recently, EMT has been found to be associated with liver and
      bile duct cell fibrosis. Analyzing the established models and chronic disease
      processes, we propose that EMT liver cells may also lose their regenerative
      capability due to phenotype changes and that the remaining liver cells may
      quickly lose their regenerative capability in liver fibrosis or cirrhosis.
      Recognizing these phenotype changes or transition cells may play an important
      role in targeting therapy to reverse fibrosis not only by disrupting the
      transition that is necessary to produce the extracellular matrix but also by
      restoring the regenerative capacity of EMT-like cells.

PMID- 23538895
TI  - Histiocytosis X revealed by diabetes insipidus and skin lesions.
AB  - Langerhans cell histiocytosis is part of a larger group of syndromes described as
      histiocytoses. The disease may involve single or multiple systems including skin
      and nervous system. Here we report an adult case where Langerhans cell
      histiocytosis presented with diabetes insipidus and cutaneous ulcers.

PMID- 23538896
TI  - Paraproteinemia-associated papular neutrophilic xanthoma of the oral commissure
      in a patient with myelodysplastic syndrome.

PMID- 23538897
TI  - Signet ring cell angiosarcoma: a hitherto unreported pitfall in the diagnosis of
      epithelioid cutaneous malignancies.
AB  - We report 2 cases of cutaneous epithelioid angiosarcoma featuring predominantly
      signet ring cells. The patients-a woman, 68 years of age, and a man, 85 years of
      age, respectively-were referred for slowly growing indurated plaques on their
      parietal and retroauricular skin. Microscopic examination showed diffuse dermal
      proliferations comprising polygonal cells and relatively abundant cytoplasm.
      Because the tumor cells often were distended by variably sized vacuoles pushing
      the nuclei to the periphery, the nuclear profile tended toward a crescent-like
      morphology. Abortive luminal formations were recognized. The tumor cells were
      positive for CD31, CD34, and D2-40/podoplanin, with no expression of epithelial
      or melanocytic markers. In 1 case, upon ultrastructural examination of paraffin
      embedded tissue-cut from wax tissue and reprocessed-the optically empty spaces
      were surrounded by a membrane with ultrastructural features identical to those of
      the outer cell membrane, suggesting that these spaces corresponded to the
      formation of primitive intracytoplasmic lumina within the tumor cells. A few
      Weibel-Palade bodies also were noted. Our report offers further evidence that
      epithelioid angiosarcoma of the skin has a broad microscopic spectrum and that
      tumors displaying a preponderant population of signet ring cells pose further
      diagnostic challenges. A brief overview of cutaneous malignant tumors in the
      differential diagnosis of signet ring cell angiosarcoma is provided.

PMID- 23538898
TI  - Sweet syndrome-like neutrophilic infiltrate as initial presentation of acute
      myelogenous leukemia.
AB  - Sweet syndrome (SS) is a neutrophilic dermatosis that may be associated with
      malignancies, especially hematological. We describe the case of a 53-year-old
      woman with a clinical presentation suggestive of SS, accompanied by pancytopenia
      and a hypercellular marrow with signs of myelodysplasia. The histopathological
      findings were characterized as an SS-like cutaneous neutrophilic infiltrate with
      atypical myeloid cells, myeloperoxidase, and BCR-ABL+, which were absent in
      peripheral blood and bone marrow aspirate. The patient was treated with systemic
      corticosteroids with resolution of symptoms and relapse 3 months later when we
      tried drug withdrawal. Eight months later, the patient was admitted to hematology
      for a mature acute myelogenous leukemia with an FLT3 mutation. The patient
      successfully underwent medullar allotransplant and is now asymptomatic (5-month
      follow-up). This case describes a patient with an acute myelogenous leukemia
      presenting initially with heralding SS-like cutaneous neutrophilic infiltrate
      with atypical BCR-ABL+ myeloid cells, as a form of aleukemia cutis. Early
      recognition of this so-called aleukemic leukemia cutis may allow clinicians to
      intervene earlier, initiating effective treatment.

PMID- 23538899
TI  - Osseous metaplasia and mature bone formation with extramedullary hematopoiesis in
      trichilemmal cyst.

PMID- 23538900
TI  - HPLC-DAD-ESI/MS identification and quantification of phenolic compounds in Ilex
      paraguariensis beverages and on-line evaluation of individual antioxidant
      activity.
AB  - "Chimarrao" and "terere" are mate (dried, toasted and milled Ilex paraguariensis
      leaves and stemlets) beverages widely consumed in South America. This paper
      describes the application of HPLC-DAD-ESI/MS method for the identification and
      quantification of caffeoylquinic acids (CQA), flavonol glycosides and purine
      alkaloids in these beverages. The beverage samples were prepared from commercial
      lots of mate from Southern Brazil. The caffeoylquinic acids, 4,5-diCQA, 3-CQA, 5
      CQA, and 4-CQA were the major compounds, having 238-289, 153-242, 183-263, and
      123-188 MUg/mL, respectively, for chimarrao and 206-265, 122-218, 164-209, 103
      169 MUg/mL, respectively, for terere. Caffeine also had high amounts while
      glycosides of quercetin and kaempferol were found at much lower levels. The
      individual antioxidant activity was also determined by an on-line system that
      measured their ABTS*+ radical scavenging activity, showing that the antioxidant
      capacity was not proportional to the concentrations of the phenolic compounds. 3
      CQA, quercetina-3-O-ramnosylglucoside, and quercetina-3-O-glucoside were the
      major contributors to the antioxidant capacity, although the quercetin glycosides
      had concentrations less than 10 times that of 3-CQA.

PMID- 23538901
TI  - Synthesis, in vitro antimycobacterial and antibacterial evaluation of IMB-070593
      derivatives containing a substituted benzyloxime moiety.
AB  - A series of novel IMB-070593 derivatives containing a substituted benzyloxime
      moiety and displaying a remarkable improvement in lipophilicity were synthesized
      and evaluated for their in vitro antimycobacterial and antibacterial activity.
      Our results reveal that the target compounds 19a-m have considerable Gram
      positive activity (MIC: <0.008-32 ug/mL), although they are generally less active
      than the reference drugs against the Gram-negative strains. In particular,
      compounds 19h, 19j, 19k and 19m show good activity (MICs: <0.008-4 ug/mL) against
      all of the tested Gram-positive strains, including ciprofloxacin (CPFX)- and/or
      levofloxacin (LVFX)-resistant MSSA, MRSA and MSSE. Moreover, compound 19l (MIC:
      0.125 ug/mL) is found to be 2-4 fold more active than the parent IMB070593, CPFX
      and LVFX against M. tuberculosis H37Rv ATCC 27294.

PMID- 23538903
TI  - Small-sized circular genomes similar to genome of porcine circovirus 2.
AB  - Circular genomes smaller than and similar to the genome of porcine circovirus 2
      were obtained from pig tissues along with the full-length genome of porcine
      circovirus 2. The 922-, 839-, and 617-nucleotide-long genomes exhibit high
      homology to the rep gene plus the origin of replication sequence of porcine
      circovirus 2.

PMID- 23538904
TI  - Draft Whole-Genome Sequence of Bacillus sonorensis Strain L12, a Source of
      Nonribosomal Lipopeptides.
AB  - The Bacillus sonorensis L12 draft genome sequence is approximately 4,647,754 bp
      in size with a G+C content of 45.2%. Over 86% of the genome contains protein
      encoding genes, including several gene clusters for de novo biosynthesis of the
      nonribosomal lipopeptides iturin, bacitracin, and fengycin, which could mean that
      the strain exhibits antifungal effects.

PMID- 23538902
TI  - Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor
      XL888 in an in vivo model of NRAS-mutant melanoma.
AB  - The HSP90 inhibitor XL888 is effective at reversing BRAF inhibitor resistance in
      melanoma, including that mediated through acquired NRAS mutations. The present
      study has investigated the mechanism of action of XL888 in NRAS-mutant melanoma.
      Treatment of NRAS-mutant melanoma cell lines with XL888 led to an inhibition of
      growth, G2-M phase cell-cycle arrest, and the inhibition of cell survival in
      three-dimensional spheroid and colony formation assays. In vitro, HSP90
      inhibition led to the degradation of ARAF, CRAF, Wee1, Chk1, and cdc2 and was
      associated with decreased mitogen-activated protein kinase (MAPK), AKT, mTOR, and
      c-jun NH2 kinase (JNK) signaling. Apoptosis induction was associated with
      increased BIM expression and a decrease in the expression of the prosurvival
      protein Mcl-1. The critical role of increased BIM and decreased Mcl-1 expression
      in the survival of NRAS-mutant melanoma cell lines was shown through siRNA
      knockdown and overexpression studies. In an animal xenograft model of NRAS-mutant
      melanoma, XL888 treatment led to reduced tumor growth and apoptosis induction.
      Important differences in the pattern of client degradation were noted between the
      in vivo and in vitro studies. In vivo, XL888 treatment led to degradation of CDK4
      and Wee1 and the inhibition of AKT/S6 signaling with little or no effect observed
      upon ARAF, CRAF, or MAPK. Blockade of Wee1, using either siRNA knockdown or the
      inhibitor MK1775, was associated with significant levels of growth inhibition and
      apoptosis induction. Together, these studies have identified Wee1 as a key target
      of XL888, suggesting novel therapeutic strategies for NRAS-mutant melanoma.

PMID- 23538905
TI  - Draft Genome Sequence of Clostridium ultunense Strain Esp, a Syntrophic Acetate
      Oxidizing Bacterium.
AB  - Clostridium ultunense strain Esp belongs to the functional group of syntrophic
      acetate-oxidizing bacteria (SAOB), which have been identified as key organisms
      for efficient biogas production from protein-rich materials. Genome analysis and
      comparative genomics might aid us to define physiological features that are
      essential for maintaining this particular syntrophic lifestyle.

PMID- 23538906
TI  - Draft Genome Sequence of Rhodococcus qingshengii Strain BKS 20-40.
AB  - We report the 5.8-Mb genome sequence of Rhodococcus qingshengii strain BKS 20-40,
      isolated from a palm tree rhizosphere soil sample from Bhitarkanika National
      Park, Odisha, India. The strain is capable of degrading cholesterol moiety. The
      draft genome of strain BKS 20-40 consists of 6,601,618 bp, with 62.4% G+C
      content.

PMID- 23538907
TI  - Draft Genome Sequence of Rhodococcus triatomae Strain BKS 15-14.
AB  - We report the 5.8-Mb genome sequence of Rhodococcus triatomae BKS 15-14, isolated
      from an ant hill soil sample, collected from Bhitarkanika Mangrove Reserve
      Forest, Odisha, India. The draft genome of strain BKS 15-14 consists of 5,824,349
      bp, with a G+C content of 69%, 5,387 protein-coding genes, and 57 RNAs.

PMID- 23538908
TI  - Co-assembled thin films of Ag nanowires and functional nanoparticles at the
      liquid-liquid interface by shaking.
AB  - In this paper, we report the fabrication of co-assembled thin films composed of
      silver nanowires (NWs) and Au nanoparticles (NPs) at the liquid-liquid interface
      (water-chloroform) by vigorous shaking. The composition of co-assembled thin
      films can be controlled by adjusting the concentration of the nanosized building
      blocks. As a versatile interfacial assembly method, other nanoparticles such as
      Ag2S and Fe3O4 NPs can also be co-assembled with Ag NWs using the same procedure.
      Meanwhile, the co-assembly state of the obtained Au NPs and Ag NWs makes a
      significant contribution to the high sensitivity of surface-enhanced Raman
      scattering (SERS) to model the molecule 3,3'-diethylthiatricarbocyanine iodide
      (DTTCI). The SERS intensities show high dependence on the molar ratio of Au NPs
      and Ag NWs and the layer number of the co-assembled thin films. This shaking
      assisted liquid-liquid assembly system has been proved to be a facile way for co
      assembling nanowires and nanoparticles, and will pave a way for further
      applications of the macroscopic co-assemblies with novel functionalities.

PMID- 23538909
TI  - Friends shrink foes: the presence of comrades decreases the envisioned physical
      formidability of an opponent.
AB  - In situations of potential violent conflict, deciding whether to fight, flee, or
      try to negotiate entails assessing many attributes contributing to the relative
      formidability of oneself and one's opponent. Summary representations can usefully
      facilitate such assessments of multiple factors. Because physical size and
      strength are both phylogenetically ancient and ontogenetically recurrent
      contributors to the outcome of violent conflicts, these attributes provide
      plausible conceptual dimensions that may be used by the mind to summarize the
      relative formidability of opposing parties. Because the presence of allies is a
      vital factor in determining victory, we hypothesized that men accompanied by male
      companions would therefore envision a solitary foe as physically smaller and less
      muscular than would men who were alone. We document the predicted effect in two
      studies, one using naturally occurring variation in the presence of male
      companions and one employing experimental manipulation of this factor.

PMID- 23538910
TI  - Lip movements affect infants' audiovisual speech perception.
AB  - Speech is robustly audiovisual from early in infancy. Here we show that
      audiovisual speech perception in 4.5-month-old infants is influenced by
      sensorimotor information related to the lip movements they make while chewing or
      sucking. Experiment 1 consisted of a classic audiovisual matching procedure, in
      which two simultaneously displayed talking faces (visual [i] and [u]) were
      presented with a synchronous vowel sound (audio /i/ or /u/). Infants' looking
      patterns were selectively biased away from the audiovisual matching face when the
      infants were producing lip movements similar to those needed to produce the heard
      vowel. Infants' looking patterns returned to those of a baseline condition (no
      lip movements, looking longer at the audiovisual matching face) when they were
      producing lip movements that did not match the heard vowel. Experiment 2
      confirmed that these sensorimotor effects interacted with the heard vowel, as
      looking patterns differed when infants produced these same lip movements while
      seeing and hearing a talking face producing an unrelated vowel (audio /a/). These
      findings suggest that the development of speech perception and speech production
      may be mutually informative.

PMID- 23538911
TI  - Mindfulness training improves working memory capacity and GRE performance while
      reducing mind wandering.
AB  - Given that the ability to attend to a task without distraction underlies
      performance in a wide variety of contexts, training one's ability to stay on task
      should result in a similarly broad enhancement of performance. In a randomized
      controlled investigation, we examined whether a 2-week mindfulness-training
      course would decrease mind wandering and improve cognitive performance.
      Mindfulness training improved both GRE reading-comprehension scores and working
      memory capacity while simultaneously reducing the occurrence of distracting
      thoughts during completion of the GRE and the measure of working memory.
      Improvements in performance following mindfulness training were mediated by
      reduced mind wandering among participants who were prone to distraction at
      pretesting. Our results suggest that cultivating mindfulness is an effective and
      efficient technique for improving cognitive function, with wide-reaching
      consequences.

PMID- 23538912
TI  - What sleeping babies hear: a functional MRI study of interparental conflict and
      infants' emotion processing.
AB  - Experiences of adversity in the early years of life alter the developing brain.
      However, evidence documenting this relationship often focuses on severe stressors
      and relies on peripheral measures of neurobiological functioning during infancy.
      In the present study, we employed functional MRI during natural sleep to examine
      associations between a more moderate environmental stressor (nonphysical
      interparental conflict) and 6- to 12-month-old infants' neural processing of
      emotional tone of voice. The primary question was whether interparental conflict
      experienced by infants is associated with neural responses to emotional tone of
      voice, particularly very angry speech. Results indicated that maternal report of
      higher interparental conflict was associated with infants' greater neural
      responses to very angry relative to neutral speech across several brain regions
      implicated in emotion and stress reactivity and regulation (including rostral
      anterior cingulate cortex, caudate, thalamus, and hypothalamus). These findings
      suggest that even moderate environmental stress may be associated with brain
      functioning during infancy.

PMID- 23538913
TI  - Stuck in the past: neural events that predict intrusions from prior trials.
AB  - Neurologically intact adults perseverate in immediate serial recall, intruding
      items from a previous trial into the current response. We applied the
      electroencephalogram/event-related-potential subsequent-memory paradigm to
      immediate serial recall to investigate the causes of these errors. In line with
      previous studies using this paradigm, results revealed that words that were
      correctly recalled elicited a greater frontal positivity during encoding when
      compared with words that were either perseverated over or not produced for some
      other reason. More surprisingly, differences were also found at encoding between
      the words perseverated into the subsequent response and words that were not
      perseverated. These findings support a theory stating that abnormalities in both
      how the current target and the previous trial are processed can contribute to
      perseveration errors. These results inform existing theories of immediate serial
      recall and theories of the control of irrelevant information.

PMID- 23538914
TI  - The thickness of musical pitch: psychophysical evidence for linguistic
      relativity.
AB  - Do people who speak different languages think differently, even when they are not
      using language? To find out, we used nonlinguistic psychophysical tasks to
      compare mental representations of musical pitch in native speakers of Dutch and
      Farsi. Dutch speakers describe pitches as high (hoog) or low (laag), whereas
      Farsi speakers describe pitches as thin (nazok) or thick (koloft). Differences in
      language were reflected in differences in performance on two pitch-reproduction
      tasks, even though the tasks used simple, nonlinguistic stimuli and responses. To
      test whether experience using language influences mental representations of
      pitch, we trained native Dutch speakers to describe pitch in terms of thickness,
      as Farsi speakers do. After the training, Dutch speakers' performance on a
      nonlinguistic psychophysical task resembled the performance of native Farsi
      speakers. People who use different linguistic space-pitch metaphors also think
      about pitch differently. Language can play a causal role in shaping nonlinguistic
      representations of musical pitch.

PMID- 23538915
TI  - Children's responses to the rubber-hand illusion reveal dissociable pathways in
      body representation.
AB  - The bodily self is constructed from multisensory information. However, little is
      known of the relation between multisensory development and the emerging sense of
      self. We investigated this question by measuring the strength of the rubber-hand
      illusion in young children (4 to 9 years old) and adults. Intermanual pointing
      showed that children were as sensitive as adults to visual-tactile synchrony cues
      for hand position, which indicates that a visual-tactile pathway to the bodily
      self matures by at least 4 years of age. However, regardless of synchrony cues,
      children's perceived hand position was closer to the rubber hand than adults'
      perceived hand position was. This indicates a second, later-maturing process
      based on visual-proprioceptive information. Furthermore, explicit feelings of
      embodiment were related only to the visual-tactile process. These findings
      demonstrate two dissociable processes underlying body representation in early
      life, and they call into question current models of body representation and
      ownership in adulthood.

PMID- 23538916
TI  - Non-ohmic behavior of carrier transport in highly disordered graphene.
AB  - We report measurements of disordered graphene probed by both a high electric
      field and a high magnetic field. By applying a high source-drain voltage, Vsd, we
      are able to study the current-voltage relation I-Vsd of our device. With
      increasing Vsd, a crossover from the linear I-Vsd regime to the non-linear one,
      and eventually to activationless-hopping transport occurs. In the activationless
      hopping regime, the importance of Coulomb interactions between charged carriers
      is demonstrated. Moreover, we show that delocalization of carriers which are
      strongly localized at low T and at small Vsd occurs in the presence of high
      electric field and perpendicular magnetic field.

PMID- 23538917
TI  - What should follow the millennium development goals?

PMID- 23538918
TI  - Effect of routine controlled cord traction as part of the active management of
      the third stage of labour on postpartum haemorrhage: multicentre randomised
      controlled trial (TRACOR).
AB  - OBJECTIVE: To assess the impact of controlled cord traction on the incidence of
      postpartum haemorrhage and other characteristics of the third stage of labour in
      a high resource setting. DESIGN: Randomised controlled trial. SETTING: Five
      university hospital maternity units in France. PARTICIPANTS: Women aged 18 or
      more with a singleton fetus at 35 or more weeks' gestation and planned vaginal
      delivery. INTERVENTIONS: Women were randomly assigned to management of the third
      stage of labour by controlled cord traction or standard placenta expulsion
      (awaiting spontaneous placental separation before facilitating expulsion). Women
      in both arms received prophylactic oxytocin just after birth. MAIN OUTCOME
      MEASURE: Incidence of postpartum haemorrhage >= 500 mL as measured in a collector
      bag. RESULTS: The incidence of postpartum haemorrhage did not differ between the
      controlled cord traction arm (9.8%, 196/2005) and standard placenta expulsion arm
      (10.3%, 206/2008): relative risk 0.95 (95% confidence interval 0.79 to 1.15). The
      need for manual removal of the placenta was significantly less frequent in the
      controlled cord traction arm (4.2%, 85/2033) compared with the standard placenta
      expulsion arm (6.1%, 123/2024): relative risk 0.69, 0.53 to 0.90); as was third
      stage of labour of more than 15 minutes (4.5%, 91/2030 and 14.3%, 289/2020,
      respectively): relative risk 0.31, 0.25 to 0.39. Women in the controlled cord
      traction arm reported a significantly lower intensity of pain and discomfort
      during the third stage than those in the standard placenta expulsion arm. No
      uterine inversion occurred in either arm. CONCLUSIONS: In a high resource
      setting, the use of controlled cord traction for the management of placenta
      expulsion had no significant effect on the incidence of postpartum haemorrhage
      and other markers of postpartum blood loss. Evidence to recommend routine
      controlled cord traction for the management of placenta expulsion to prevent
      postpartum haemorrhage is therefore lacking. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01044082.

PMID- 23538919
TI  - Association between physicians' experience after training and maternal
      obstetrical outcomes: cohort study.
AB  - OBJECTIVE: To assess the association between obstetricians' years of experience
      after training and the maternal complications of their patients during their
      first 40 years of post-residency practice. DESIGN: Retrospective cohort analysis.
      SETTING: Obstetrical discharges from acute care hospitals in Florida and New York
      between academic years 1992 and 2009. POPULATION: 6,704,311 deliveries performed
      by 5175 obstetricians. MAIN OUTCOME MEASURE: Three composite measures of maternal
      complication rates per physician year from vaginal and cesarean births separately
      and combined, adjusted for secular trends. RESULTS: Obstetricians' maternal
      complication rates declined during the first three decades after completion of
      residency. The improvement was largest in the first decade and diminished
      thereafter. For all deliveries, the change was -0.21 (95% confidence interval 
      0.23 to -0.19) percentage points per year in the first decade, -0.11 (-0.13 to 
      0.09) percentage points per year in the second decade, and -0.05 (-0.08 to -0.01)
      percentage points in the third decade (P<0.001 for second to first decade
      comparison; P=0.001 for third to second decade comparison). The patterns were
      comparable for cesarean deliveries and vaginal deliveries and across several
      sensitivity checks. CONCLUSIONS: Among obstetricians practicing in Florida and
      New York, those with more years of experience had fewer maternal complications.
      This association persisted over the first three decades of practice but
      diminished in magnitude.

PMID- 23538920
TI  - Leukaemia update. Part 1: diagnosis and management.

PMID- 23538921
TI  - Inaccuracy of forehead thermometers.

PMID- 23538922
TI  - Understanding variation in utilisation: start with health needs.

PMID- 23538923
TI  - Liverpool care pathway is a nice idea--pity about the practice.

PMID- 23538924
TI  - Funding is insufficient for the NHS to work at weekend as it does in the week.

PMID- 23538925
TI  - Whether the NHS works at weekends as it does in the week is a question of cost
      effectiveness.

PMID- 23538926
TI  - A proper 24/7 emergency care service is needed in the NHS.

PMID- 23538927
TI  - Commentary: New development goals must focus on social determinants of health.

PMID- 23538928
TI  - Medicine should be a "gift relationship" not a commercial transaction.

PMID- 23538929
TI  - Big brand pharma on the hook for generic problems.

PMID- 23538930
TI  - Conversion of methacrylate into 2-hydroxy-2-methylpropionate ligands in the
      coordination sphere of a Ag-Zr oxo cluster.
AB  - Reaction of Zr(O(n)Bu)4 and silver acetate with methacrylic acid afforded a mixed
      metal cluster with a Ag2Zr8O6 core and both methacrylate and 2-hydroxy-2
      methylpropionate ligands.

PMID- 23538931
TI  - Inflammasomes: microtubules pull mitochondria to NLRP3.

PMID- 23538932
TI  - The impact of children with disabilities on parent health-related quality of life
      and family functioning in Kelantan and its associated factors.
AB  - OBJECTIVES: Caring for children with disabilities brings about a significant
      impact on the parents and families. The purposes of this study were to determine
      the impact of having children with disabilities on parents' health-related
      quality of life (HRQOL), family functioning, and total family impact and to
      identify the associated factors. METHOD: A total of 425 parents/caregivers of
      children with disabilities who were registered to community-based rehabilitation
      centers in 5 districts in Kelantan, Malaysia, participated in this study. The
      Malay version of PedsQL Family Impact Module was used as research instrument.
      General linear regression was applied to analyze the association between family
      impact scores (Total Impact, Parent HRQOL Summary, and Family Functioning
      Summary) and study factors using Stata/SE 11 software. RESULTS: The mean (SD)
      Total Impact Score and Parent HRQOL Summary Score of the parents/caregivers was
      75.1 (16.85) and 75.0 (18.74) respectively, and the median (IQR) of Family
      Functioning Summary Score was 84.4 (28.13). Mothers, non-Malays, and widowed
      parents/caregivers, parents/caregivers having male children with disabilities,
      and children with more complex disability had significantly lower parent HRQOL
      and family functioning. CONCLUSIONS: Both parents/caregivers' characteristics and
      children's characteristics contributed to family impact in local setting. Results
      of this study emphasize the importance of the whole family involvement as the
      focus of services and supports by health care providers.

PMID- 23538933
TI  - UV-irradiated 7-dehydrocholesterol coating on polystyrene surfaces is converted
      to active vitamin D by osteoblastic MC3T3-E1 cells.
AB  - The aim of the present study was to determine the effects of UV irradiation on
      the conversion of 7-dehydrocholesterol (7-DHC), which has been coated onto a
      polystyrene surface, to cholecalciferol (D3), and the resulting effect on the
      formation of vitamin D (1,25-D3) by MC3T3-E1 cells. The changes in gene
      expression of the enzymes regulating its hydroxylation, Cyp27b1 and Cyp27a1, were
      monitored as well as the net effect of the UV-treated 7-DHC coating on cell
      viability and osteoblast differentiation. MC3T3-E1 cells were found to express
      the enzymes required for synthesizing active 1,25-D3, and we found a dose
      dependent increase in the production of both 25-D3 and 1,25-D3 levels for UV
      activated 7-DHC samples unlike UV-untreated ones. Cell viability revealed no
      cytotoxic effect for any of the treatments, but only for the highest dose of 7
      DHC (20 nmol per well) that was UV-irradiated. Furthermore, osteoblast
      differentiation was increased in cells treated with some of the higher doses of 7
      DHC when UV-irradiated, as shown by collagen-I, osterix and osteocalcin relative
      mRNA levels. The conversion of 7-DHC to preD3 exogenously by UV irradiation and
      later to 25-D3 by MC3T3-E1 cells was determined for the optimum 7-DHC dose (0.2
      nmol per well), i.e. 8.6 +/- 0.7% of UV-activated 7-DHC was converted to preD3
      and 6.7 +/- 2.8% of preD3 was finally converted to 25-D3 under the conditions
      studied. In conclusion, we demonstrate that an exogenous coating of 7-DHC, when
      UV-irradiated, can be used to endogenously produce active vitamin D. We hereby
      provide the scientific basis for UV-activated 7-DHC coating as a feasible
      approach for implant therapeutics focused on bone regeneration.

PMID- 23538934
TI  - Vanishing lung syndrome (idiopathic giant bullous emphysema).

PMID- 23538935
TI  - Bone mineral density patterns in vitamin D deficient African American men with
      sickle cell disease.
AB  - OBJECTIVE: To describe bone mineral density (BMD) patterns by densitometry in
      adult African American (AA) men with sickle cell disease (SCD) who are vitamin D
      deficient (Vit DD). INCLUSION/EXCLUSION CRITERIA: All SCD phenotypes were
      eligible. Those with chronic renal failure or hyperparathyroidism were excluded.
      DATA COLLECTION: Demographics, body mass index and SCD genotype. LABORATORY:
      Albumin, ferritin, calcium, phosphorus, 25-hydroxy vitamin D and intact
      parathyroid hormone were obtained. BMD, T and Z scores: T scores at the lumbar
      spine were used to categorize normal, osteopenia and osteoporosis based on World
      Health Organization criteria. STATISTICAL ANALYSES: Mean +/- standard deviation
      was used to describe continuous data, whereas categorical data were described by
      counts and percentages. The chi test was used to analyze categorical variables;
      Student's t test or one-way analysis of variance, when appropriate, was used to
      compare continuous variables. Rates of osteopenia-osteoporosis were determined,
      and the parameter with 95% confidence interval (CI) of a proportion was
      constructed. All tests were 2-sided, and a P <= 0.05 was considered statistically
      significant. We used StatView Version 5.01 (SAS institute Inc, Cary, NC) for the
      statistical analysis. RESULTS: Seventy-eight AA men with SCD disease and Vit DD
      were enrolled in this study. We found that 42% of the men studied had low-BMD
      (osteopenia or osteoporosis) using T scores at the lumbar spine to establish
      densitometry strata. The prevalence of osteoporosis was 14%. CONCLUSIONS: A large
      proportion of adult AA men with SCD and Vit DD showed low BMD.

PMID- 23538936
TI  - First use of a drug-eluting balloon in the treatment of acute renal artery
      occlusion and in-stent restenosis.
AB  - In-stent restenosis in a renal artery (RA) of a solitary functioning kidney is a
      serious complication of RA stenting. Drug-eluting balloons (DEB) have emerged as
      a novel way to manage restenosis. In this paper, the authors reported the first
      use of a DEB in the treatment of severe in-stent restenosis and thrombosis of a
      drug-eluting stent deployed in a RA. The patient presented with oligo-anuria and
      a serum creatinine (Scr) of 9 mg/dL that improved back to baseline of 2 mg/dL
      after the successful procedure. The optimal use of DEB in similar cases will have
      to be determined by larger clinical trials.

PMID- 23538937
TI  - Selenium toxicity from a misformulated dietary supplement, adverse health
      effects, and the temporal response in the nail biologic monitor.
AB  - Use of dietary supplements in the U.S. has increased steadily over the last 25
      years. While misformulation is uncommon, the consequences can be serious. A March
      2008 voluntary market recall removed supplement products responsible for the most
      serious selenium toxicity outbreak that has occurred in the U.S. We quantified
      selenium concentrations in the misformulated supplement products, measured the
      temporal response in the nail biologic monitor, and associated exposure to self
      reported selenosis symptoms. Subjects recruited through state health departments
      and referrals provided samples of the misformulated supplement products, exposure
      information, monthly toenail and or fingernail clippings or onycholysitic nail
      fragments, and listed their newly onset adverse health effects attributed to
      selenium toxicity. Ninety-seven subjects enrolled and submitted at least one test
      sample. Peak selenium concentrations (up to 18.3 and 44.1 MUg/g for toenails and
      fingernails, respectively) were measured. Multiple samples (52 total) of all six
      recalled supplement lots were analyzed ranging from 22,300 to 32,200 MUg selenium
      per daily dose. Average consumption was 30.9 +/- 13.9 doses; 73 subjects provided
      follow-up data on selenosis symptoms at 2.50 +/- 0.14 years. Nail samples
      accurately reflect exposure in this selenium toxicity outbreak, which resulted in
      long-term/permanent adverse health effects.

PMID- 23538938
TI  - Standardised parenteral nutrition.
AB  - Parenteral nutrition (PN) has become an integral part of clinical management of
      very low birth weight premature neonates. Traditionally different components of
      PN are prescribed individually considering requirements of an individual neonate
      (IPN). More recently, standardised PN formulations (SPN) for preterm neonates
      have been assessed and may have advantages including better provision of
      nutrients, less prescription and administration errors, decreased risk of
      infection, and cost savings. The recent introduction of triple-chamber bag that
      provides total nutrient admixture for neonates may have additional advantage of
      decreased risk of contamination and ease of administration.

PMID- 23538939
TI  - Effect of diets differing in glycemic index and glycemic load on cardiovascular
      risk factors: review of randomized controlled-feeding trials.
AB  - Despite a considerable amount of data available on the relationship between
      dietary glycemic index (GI) or load (GL) and cardiovascular disease (CVD) risk
      factors, in aggregate, the area remains unsettled. The aim of the present review
      was to summarize the effect of diets differing in GI/GL on CVD risk factors, by
      examining randomized controlled-feeding trials that provided all food and
      beverages to adult participants. The studies included a low and high GI/GL diet
      phase for a minimum of four weeks duration, and reported at least one outcome
      related to CVD risk; glucose homeostasis, lipid profile or inflammatory status.
      Ten publications representing five trials were identified. The low GI/GL compared
      to the high GI/GL diet unexpectedly resulted in significantly higher fasting
      glucose concentrations in two of the trials, and a lower area under the curve for
      glucose and insulin in one of the two studies during an oral glucose tolerance
      test. Response of plasma total, low density lipoprotein and high density
      lipoprotein cholesterol concentrations was conflicting in two of the studies for
      which data were available. There was either weak or no effect on inflammatory
      markers. The results of the five randomized controlled trials satisfying the
      inclusion criteria suggest inconsistent effects of the GI/GL value of the diet on
      CVD risk factors.

PMID- 23538940
TI  - Issues of fish consumption for cardiovascular disease risk reduction.
AB  - Increasing fish consumption is recommended for intake of omega-3 (n-3) fatty
      acids and to confer benefits for the risk reduction of cardiovascular disease
      (CVD). Most Americans are not achieving intake levels that comply with current
      recommendations. It is the goal of this review to provide an overview of the
      issues affecting this shortfall of intake. Herein we describe the relationship
      between fish intake and CVD risk reduction as well as the other nutritional
      contributions of fish to the diet. Currently recommended intake levels are
      described and estimates of fish consumption at a food disappearance and
      individual level are reported. Risk and benefit factors influencing the choice to
      consume fish are outlined. The multiple factors influencing fish availability
      from global capture and aquaculture are described as are other pertinent issues
      of fish nutrition, production, sustainability, and consumption patterns. This
      review highlights some of the work that needs to be carried out to meet the
      demand for fish and to positively affect intake levels to meet fish intake
      recommendations for CVD risk reduction.

PMID- 23538941
TI  - The association of ambient air pollution and traffic exposures with selected
      congenital anomalies in the San Joaquin Valley of California.
AB  - Congenital anomalies are a leading cause of infant mortality and are important
      contributors to subsequent morbidity. Studies suggest associations between
      environmental contaminants and some anomalies, although evidence is limited. We
      aimed to investigate whether ambient air pollutant and traffic exposures in early
      gestation contribute to the risk of selected congenital anomalies in the San
      Joaquin Valley of California, 1997-2006. Seven exposures and 5 outcomes were
      included for a total of 35 investigated associations. We observed increased odds
      of neural tube defects when comparing the highest with the lowest quartile of
      exposure for several pollutants after adjusting for maternal race/ethnicity,
      education, and multivitamin use. The adjusted odds ratio for neural tube defects
      among those with the highest carbon monoxide exposure was 1.9 (95% confidence
      interval: 1.1, 3.2) compared with those with the lowest exposure, and there was a
      monotonic exposure-response across quartiles. The highest quartile of nitrogen
      oxide exposure was associated with neural tube defects (adjusted odds ratio =
      1.8, 95% confidence interval: 1.1, 2.8). The adjusted odds ratio for the highest
      quartile of nitrogen dioxide exposure was 1.7 (95% confidence interval: 1.1,
      2.7). Ozone was associated with decreased odds of neural tube defects. Our
      results extend the limited body of evidence regarding air pollution exposure and
      adverse birth outcomes.

PMID- 23538942
TI  - Latent transition models to study women's changing of dietary patterns from
      pregnancy to 1 year postpartum.
AB  - Latent class models are useful for classifying subjects by dietary patterns. Our
      goals were to use latent transition models to identify dietary patterns during
      pregnancy and postpartum, to estimate the prevalence of these dietary patterns,
      and to model transition probabilities between dietary patterns as a function of
      covariates. Women who were enrolled in the Pregnancy, Infection, and Nutrition
      Study (University of North Carolina, 2000-2005) were followed for 1 year
      postpartum, and their diets were assessed in the second trimester and at 3 and 12
      months postpartum (n = 519, 484, and 374, respectively) by using a food frequency
      questionnaire. After adjusting for energy intake, parity, smoking status, race,
      and education, we identified 3 dietary patterns and named them "prudent," "health
      conscious Western," and "Western." Nulliparas were 2.9 and 2.1 times more likely
      to be in the "prudent" class than the "health conscious Western" or the "Western"
      class, respectively. The 3 dietary patterns were very stable, with the "health
      conscious Western" class being the least stable; the probability for staying in
      the same class was 0.74 and 0.87 at 3 and 12 months postpartum, respectively.
      Breastfeeding mothers were more likely than nonbreastfeeding mothers to switch
      dietary pattern class (P = 0.0286). Except for breastfeeding mothers, most women
      did not switch dietary patterns from pregnancy to postpartum.

PMID- 23538943
TI  - Re: "Comparisons of the strength of associations with future type 2 diabetes risk
      among anthropometric obesity indicators, including waist-to-height ratio: a meta
      analysis".

PMID- 23538944
TI  - [Psychiatry with open doors. Part 1: Rational for an open door for acute
      psychiatry].
AB  - Despite the reform efforts of the last decades modern acute psychiatry still
      stands between conflicting priorities in everyday practice. The protection of
      patient autonomy might conflict with a regulatory mandate of psychiatry in
      societal contexts and the necessity of coercive measures and involuntary
      treatment might become problematic with respect to presumed but contentious
      interests of the patient. The conflicts particularly concern questions of
      involuntary commitment, door closing, coercive and isolation measures. Research
      on the topic of therapeutic effectiveness of these practices is rare.
      Accordingly, the practice depends on the federal state, hospital and ward and is
      very heterogeneous. Epidemiological prognosis predicts an increase of psychiatric
      disorders; however, simultaneously in terms of medical ethics the warranty of
      patient autonomy, shared decision-making and informed consent in psychiatry
      become increasingly more important. This challenges structural and practical
      changes in psychiatry, particularly in situations of self and third party
      endangerment which are outlined and a rationale for an opening of the doors in
      acute psychiatric wards is provided.

PMID- 23538946
TI  - Chemistry and applications of metal complexes.

PMID- 23538945
TI  - Exact confidence interval estimation for the difference in diagnostic accuracy
      with three ordinal diagnostic groups.
AB  - In the cases with three ordinal diagnostic groups, the important measures of
      diagnostic accuracy are the volume under surface (VUS) and the partial volume
      under surface (PVUS) which are the extended forms of the area under curve (AUC)
      and the partial area under curve (PAUC). This article addresses confidence
      interval estimation of the difference in paired VUS s and the difference in
      paired PVUS s. To focus especially on studies with small to moderate sample
      sizes, we propose an approach based on the concepts of generalized inference. A
      Monte Carlo study demonstrates that the proposed approach generally can provide
      confidence intervals with reasonable coverage probabilities even at small sample
      sizes. The proposed approach is compared to a parametric bootstrap approach and a
      large sample approach through simulation. Finally, the proposed approach is
      illustrated via an application to a data set of blood test results of anemia
      patients.

PMID- 23538947
TI  - Cytokine IL-6 secretion by trophoblasts regulated via sphingosine-1-phosphate
      receptor 2 involving Rho/Rho-kinase and Rac1 signaling pathways.
AB  - Various cytokines derived from placental cells are essential for normal placenta
      development and successful pregnancy. Interleukin-6 (IL-6) is a multifunctional
      cytokine produced by extravillous and cytotrophoblasts regulating the functions
      of these cells, e.g. migration, invasion, trophoblast differentiation and
      proliferation. In macrophages, newly synthesized IL-6 accumulates in the Golgi
      complex and exits in tubulovesicular carriers fused with recycling endosomes and
      secreted as a soluble protein. Sphingosine-1-phosphate (S1P) induces various
      cytokine secretions including IL-6 in different cell types. The signaling
      mechanisms regulating the IL-6 secretion are unknown. In this study, we found
      that S1PR2 was the major S1P receptor being expressed in BeWo cells. S1P
      regulated IL-6 protein secretion in early phase (6 h) and gene expression in
      later phase (24 h). IL-6 secretion was completely inhibited via inhibitor of
      transcription (Actinomycin D) or protein synthesis (Cycloheximide) confirming
      that IL-6 releases constitutively from BeWo cells. By using specific S1PR2
      inhibitor JTE-013 and S1PR2 gene silencing, we found that S1PR2 was the main
      receptor that regulates IL-6 secretion. Furthermore, S1P induced RhoGTPases
      dependent pathways that are required for IL-6 secretion. Pretreatment of cells
      with specific Rho-kinase inhibitor (Y27632) and Rac1 inhibitor (NSC23766)
      drastically inhibited S1P-induced IL-6 secretion. By using a specific
      Phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), we found that basal
      activity of PI3K was required for secretion but was independent of S1P/S1PR2 axis
      activation. In summary, we report first time that binding of S1P to S1PR2
      activates multiple RhoGTPases-dependent pathways that coordinate with PI3K
      pathway for secretion of IL-6 in BeWo cells. 

PMID- 23538950
TI  - Stonemeal of Amazon soils with sediments from reservoirs: a case study of
      remineralization of the Tucurui degraded land for agroforest reclamation.
AB  - This study suggests the employment of accumulated sediments in the reservoir of
      Tucurui (Para /Brazil) to remineralize the surrounding degraded soils. The
      approach was based on the principles of stonemeal technology. It suggests that
      the soil can be rejuvenated by crushed rocks rich in macro and micronutrients.
      Removal of the sediments for agricultural use will bring benefits to family
      farmers and increase the life cycle of the reservoir and, therefore, energy
      generation. Geochemical data on retained sediments, soils and rocks in the area
      of influence of the reservoir were evaluated regarding nutrient transport
      mechanisms and soil-fertility potential. Results show that sediments from the
      reservoir contain nutrients levels at least one order of magnitude greater than
      average Amazon region soils. Our data on soil use and occupation in the region
      show the degradation areas which could be recovered by stonemeal techniques.
      Thence, an Agroforestry System was installed, with 12 plots where different
      mixtures of sediments removed from the reservoir were used, along with crushed
      rock with or without the addition of NPK and manure. The experiments showed that
      maximum crop yield and plant growth were attained in the plots where a mixture of
      sediments, crushed rocks and manure were added.

PMID- 23538951
TI  - Late Quaternary landscape evolution of northeastern Amazonia from pollen and
      diatom records.
AB  - The main goal of this study was to reconstruct the Late Pleistocene-Holocene
      floristic composition in an area of the northern Brazilian Amazonia, comparing
      the results with other Amazonian localities in order to discuss the factors that
      have influenced phytophysiognomic changes over this time period. The work in
      eastern Marajo Island at the mouth of the Amazonas River was approached based on
      analysis of 98 pollen and diatom samples from core data distributed along a
      proximal to distal transect of a paleoestuarine system. The results indicated
      high concentration of Rhizophora, associated with arboreal pollen grains typical
      of the modern Amazonian rainforest during the last 40,000 cal yrs BP. Pollen
      composition also included wetland herbs. Diatoms were dominated by marine and
      fresh water taxa. Wetland forest, mangrove and, subordinately herbs remained
      constant during most of the latest Pleistocene-early/middle Holocene. At 5,000
      cal yrs BP, there was a distinguished change from forest and mangrove to wet
      grassland savanna due to sea level fluctuation. As marine influence decreased,
      the estuary gave rise to fresh water lacustrine and swamp environments, with
      establishment of herbaceous campos. A main conclusion from this study is that
      solely the occurrence of herbaceous savanna can not be used as a definitive
      indicator of past dry climates in Amazonian areas.

PMID- 23538954
TI  - Pedology and plant physiognomies in the Cerrado, Brazil.
AB  - This study was carried out in Paraopeba National Reserve. It aims to classify and
      evaluate the soil of the studied area and to verify the influence of soil
      attributes on vegetation by testing the following hypotheses: 1) under woodland
      physiognomies (Cerradao) the soil fertility is higher and the Al content lower;
      2) open savanna occurs only in areas with high Al contents. For this purpose,
      representative soils in the Paraopeba National Reserve were mapped, identified,
      and samples from five profiles were analyzed. The environmental gradient was
      easily observed by principal components analyses, where the differences between
      the sites were highlighted. The Spearman correlation was used to verify the
      hypothesis. The correlation between vegetation (basal area, density, and
      richness) and soil (K, Ca2+, and Al3+) was statistically significant. The
      hypotheses were accepted, but hypothesis 1 only partially. Soil features seem to
      have an influence on the Cerrado phytophysiognomies and structure. Available
      phosphorous was an important factor for the maintenance of woodland Cerrado.
      Also, exchangeable Al3+ plays a major role in the establishment of different
      Cerrado physiognomies in Paraopeba National Reserve.

PMID- 23538955
TI  - New turtle egg fossil from the Upper Cretaceous of the Laiyang Basin, Shandong
      Province, China.
AB  - A new type of turtle egg fossil was established: Emydoolithus laiyangensis oogen.
      et oosp. nov.. Based on its elliptical morphological shape, rigid eggshells, and
      eggshell characteristics, it is different from other types of round chelonian egg
      fossils. It is the second chelonian egg fossil found in Cretaceous in China. This
      discovery shows the Laiyang ecosystem in Late Cretaceous is more diversified than
      previously thought.

PMID- 23538956
TI  - The largest flying reptile from Gondwana: a new specimen of Tropeognathus cf. T.
      mesembrinus Wellnhofer, 1987 (Pterodactyloidea, Anhangueridae) and other large
      pterosaurs from the Romualdo Formation, Lower Cretaceous, Brazil.
AB  - A very large pterosaur (MN 6594-V) from the Romualdo Formation (Aptian/Albian),
      Santana Group, Araripe Basin, is described. The specimen is referred to
      Tropeognathus cf. T. mesembrinus mainly due to the presence of a low and blunt
      frontoparietal crest, the comparatively low number of teeth and the inclined
      dorsal part of the occipital region. Two distinct wingspan measurements for
      pterosaurs are introduced: the maximized wingspan (maxws), which essentially
      consists of doubling the addition of all wing elements and the length of the
      scapula or the coracoid (the smaller of the two), and the normal wingspan (nws),
      which applies a reducing factor (rfc) to the maximized wingspan to account for
      the natural flexures of the wing. The rfc suggested for pteranodontoids is 5%. In
      the case of MN 6594-V, the maxws and nws are 8.70 m and 8.26 m, respectively,
      making it the largest pterosaur recovered from Gondwana so far. The distal end of
      a larger humerus (MCT 1838-R) and a partial wing (MPSC R 1395) are also described
      showing that large to giant flying reptiles formed a significant part of the
      pterosaur fauna from the Romualdo Formation. Lastly, some comments on the
      nomenclatural stability of the Santana deposits are presented.

PMID- 23538957
TI  - Developmental pathway from leaves to galls induced by a sap-feeding insect on
      Schinus polygamus (Cav.) Cabrera (Anacardiaceae).
AB  - Galling sap-feeding insects are presumed to cause only minor changes in host
      plant tissues, because they usually do not require development of nutritive
      tissues for their own use. This premise was examined through comparison of the
      histometry, cytometry and anatomical development of non-galled leaves and galls
      of Calophya duvauae (Scott) (Hemiptera: Calophyidae) on Schinus polygamus (Cav.)
      Cabrera (Anacardiaceae). Cell fates changed from non-galled leaves to galls
      during the course of tissue differentiation. C. duvauae caused changes in dermal,
      ground, and vascular systems of the leaves of S. polygamus. Its feeding activity
      induced the homogenization of the parenchyma, and the neoformation of vascular
      bundles and trichomes. The histometric and cytometric data revealed compensatory
      effects of hyperplasia and cell hypertrophy in the epidermis, with hyperplasia
      predominating in the adaxial epidermis. There was a balance between these
      processes in the other tissues. Thus, we found major differences between the
      developmental pathways of non-galled leaves and galls. These changes were
      associated with phenotypic alterations related to shelter and appropriate
      microenvironmental conditions for the gall inducer. The nondifferentiation of a
      typical nutritive tissue in this case was compared to other non-phylogenetically
      related arthropod gall systems, and is suggested to result from convergence
      associated with the piercing feeding apparatus of the corresponding gall-inducer.

PMID- 23538958
TI  - Wild birds as pets in Campina Grande, Paraiba State, Brazil: an ethnozoological
      approach.
AB  - Birds are one of the animals most widely used by humans and are highly valued as
      pets. The present work reports the use of wild birds as pets in the city of
      Campina Grande, Paraiba State (PB), Brazil. The owners' choice and perceptions of
      the species ecology was assessed as well. The methodology employed included
      unstructured and semi-structured interviews, guided tours and direct
      observations. A total of 26 bird species distributed among ten families and four
      orders were identified. The most frequently encountered order was Passeriformes
      (76.9%), with a predominance of the family Emberizidae (34.6%). The specimens
      kept as pets were principally obtained in public markets or between the breeders
      themselves. The popularity of birds as pets, compounded by the inefficiency of
      official controls over the commerce of wild animals has stimulated the illegal
      capture and breeding of wild birds in Campina Grande.

PMID- 23538959
TI  - Brachyuran and anomuran crabs associated with Schizoporella unicornis
      (Ectoprocta, Cheilostomata) from southeastern Brazil.
AB  - The main goals of this investigation were to describe the community structure of
      anomuran and brachyuran crabs inhabiting reefs constituted by colonies of
      Schizoporella unicornis, and to provide a species importance ranking for this
      community. Collections were carried out on S. unicornis reefs at two-month
      intervals from May 2003 to May 2004, in the rocky sublittoral of the southeastern
      Brazilian coast. Relative abundance and occurrence were used to rank these
      species in the hierarchy importance. A total of 2,018 individuals were obtained,
      in 11 families, 22 genera and 31 species. Porcellanidae and Pilumnidae were the
      most abundant families, comprising respectively almost 60% and 15% of individuals
      sampled. The species ranking indicated four main groups A, B, C and D, with group
      A subdivided. Subgroup A1 contained 9 species, including the species of greatest
      ecological importance for community regarding abundance and occurrence. The great
      abundance of crabs associated with S. unicornis seems to be the result of its
      recognized importance during the crab developmental cycle, and as shelter and
      food for some Decapod species. These observations reveal the importance of
      conserving the areas occupied by these reef colonies, which appear to be an
      important environment for maintaining local biodiversity.

PMID- 23538960
TI  - Immature stages of Spodoptera albula (Walker) (Lepidoptera: Noctuidae):
      developmental parameters and host plants.
AB  - This study aimed to detail the temporal and morphological parameters of the
      immature stages of Spodoptera albula (Walker 1857) under controlled conditions
      (25 +/- 1 degrees C, 70 +/- 10% RH and 14 hour photophase) and to gather
      information about their larval host plants. For this purpose, a new rearing
      method and artificial diet was employed and validated. The viability of the egg,
      larval, pupal and pre-pupal stages was 94.54, 97.33, 93.84 and 92.34%,
      respectively. The average duration of the egg, larval, pupal and pre-pupal stages
      was 4.14, 16.37, 1.69, and 9.34 days, respectively. During the larval stage,
      80.85% of females and 93.99% of males passed through six and remaining through
      seven instars, with significant larval protandry. The larvae that developed
      through six and seven instars exhibited a mean growth rate of 1.58 and 1.48,
      respectively. Fifty five host plant species belonging to 29 families are listed.
      The female pupae were significantly larger, exhibiting protogyny. Both the
      rearing methods as well as the larval diet proved adequate, providing more
      detailled observations of the biological cycle, especially the larval stage, and
      resulting in an overall survival of almost 80%.

PMID- 23538961
TI  - Growth and hematology of juvenile pacu Piaractus mesopotamicus (Holmberg 1887)
      fed with increasing levels of vitamin E (DL-alpha-tocopheryl acetate).
AB  - Intensive fish production systems are characterized by 100% artificial feeding,
      so any dietary imbalances or deficiencies may lead to diseases outbreaks and
      economic losses. This study was set out to determine the effects of increasing
      levels of dietary vitamin E on growth and hematology of juvenile pacu. Fishes
      were fed for 90 days, twice a day until apparent satiation with semi-purified
      diets containing 0.0; 25; 50; 150; 300 or 600 mg.kg-1 diet DL-alpha-tocopheryl
      acetate in a completely randomized design trial (n=4); biometrical and
      hematological data were collected and analyzed. Fishes fed with vit E diet (150
      mg.kg-1) showed higher (p<0.05) weight gain and specific growth. Hematocrit,
      erythroblast number and total plasma protein were increased (p<0.05) in fishes
      fed diet with no vit E diet. Vitamin E supplementation in artificial diets for
      pacu is essential for growth and maintenance of normal erythropoiesis.

PMID- 23538962
TI  - Retained laser fibre: insights and management.
AB  - OBJECTIVES: To describe a case of retained endovenous laser fibre. To review the
      literature and Food and Drug Administration device failure reports. To suggest
      protocols for avoiding this complication and a method of removal. METHODS: A case
      of retained fibre removal is described. Fibre removal techniques in vivo and ex
      vivo in a bovine model on the laboratory bench are presented. RESULTS: Successful
      in vivo and ex vivo fibre removal was performed using duplex ultrasound scan
      guided phlebectomy techniques. Unexplained measured fibre-length discrepancies
      due to misleading manufacturer's packaging was discovered. CONCLUSIONS: Simple
      ultrasound-guided micro-phlebectomy techniques can be used to remove retained
      laser fibres in the office environment. Laser fibre length measurements before
      and after treatment are recommended. Some preventive guidelines are described to
      avoid, or at least diagnose immediately, this complication, such as the 'Laser
      Eclipse Sign'.

PMID- 23538963
TI  - Venous leg ulcer in the context of chronic venous disease.
AB  - OBJECTIVES: Chronic venous disease (CVD) is a frequent disorder with a high
      socioeconomic impact. Little is known about the possible differences between
      healed ulcer (C5 group) and active ulcer (C6 group) in terms of disease severity
      and quality of life (QoL). Our aim was to determine the possible differences in
      severity disease and QoL between the C5-C6 and C1 (control) group. METHODS: Data
      from a national, multicentre, observational and cross-sectional study (n = 1598)
      were used to compare three groups of CVD: C1 (n = 243), C5 (n = 136) and C6 (n =
      70). CVD severity was assessed with the Venous Clinical Severity Score (VCSS) and
      QoL with the Short Form 12 Health Survey (SF-12) and Chronic Lower Limb Venous
      Insufficiency Questionnaire (CIVIQ-20). RESULTS: Patients with active ulcers had
      a higher mean total VCSS than patients with healed ulcers (P < 0.05). Both SF-12
      and CIVIQ-20 QoL questionnaires indicated a poorer QoL in patients with ulcers
      than in those with C1 (P < 0.05). Compared with the C5 group, patients with
      active ulcers (C6) had lower QoL scores, but the differences were not
      statistically significant. CONCLUSIONS: Patients with venous leg ulcers (C5-C6)
      are associated with high severity and poor QoL. However, the healing of a leg
      ulcer did not contribute to improvement of QoL.

PMID- 23538964
TI  - Empirical null distribution based modeling of multi-class differential gene
      expression detection.
AB  - In this paper, we study the multi-class differential gene expression detection
      for microarray data. We propose a likelihood based approach to estimating an
      empirical null distribution to incorporate gene interactions and provide more
      accurate false positive control than the commonly used permutation or theoretical
      null distribution based approach. We propose to rank important genes by p-values
      or local false discovery rate based on the estimated empirical null distribution.
      Through simulations and application to a lung transplant microarray data, we
      illustrate the competitive performance of the proposed method.

PMID- 23538965
TI  - Private healthcare must improve its transparency, quality, and cost, just like
      the NHS, says Bupa leader.

PMID- 23538966
TI  - Monolithic integration of nanoscale tensile specimens and MEMS structures.
AB  - Nanoscale materials often have stochastic material properties due to a random
      distribution of material defects and an insufficient number of defects to ensure
      a consistent average mechanical response. Current methods to measure the
      mechanical properties employ MEMS-based actuators. The nanoscale specimens are
      typically mounted manually onto the load platform, so the boundary conditions
      have random variations, complicating the experimental measurement of the
      intrinsic stochasticity of the material properties. Here we show methods for
      monolithic integration of a nanoscale specimen co-fabricated with the loading
      platform. The nanoscale specimen is gold with dimensions of ~40 nm thickness, 350
      +/- 50 nm width, and 7 MUm length and the loading platform is an interdigitated
      electrode electrostatic actuator. The experiment is performed in a scanning
      electron microscope and digital image correlation is employed to measure
      displacements to determine stress and strain. The ultimate tensile strength of
      the nanocrystalline nanoscale specimen approaches 1 GPa, consistent with
      measurements made by other nanometer scale sample characterization methods on
      other material samples at the nanometer scale, as well as gold samples at the
      nanometer scale. The batch-compatible microfabrication method can be used to
      create nominally identical nanoscale specimens and boundary conditions for a
      broad range of materials.

PMID- 23538967
TI  - Selection of distinct populations of dentate granule cells in response to inputs
      as a mechanism for pattern separation in mice.
AB  - The hippocampus is critical for episodic memory and computational studies have
      predicted specific functions for each hippocampal subregion. Particularly, the
      dentate gyrus (DG) is hypothesized to perform pattern separation by forming
      distinct representations of similar inputs. How pattern separation is achieved by
      the DG remains largely unclear. By examining neuronal activities at a population
      level, we revealed that, unlike CA1 neuron populations, dentate granule cell
      (DGC) ensembles activated by learning were not preferentially reactivated by
      memory recall. Moreover, when mice encountered an environment to which they had
      not been previously exposed, a novel DGC population-rather than the previously
      activated DGC ensembles that responded to past events-was selected to represent
      the new environmental inputs. This selection of a novel responsive DGC population
      could be triggered by small changes in environmental inputs. Therefore, selecting
      distinct DGC populations to represent similar but not identical inputs is a
      mechanism for pattern separation. DOI:http://dx.doi.org/10.7554/eLife.00312.001.

PMID- 23538969
TI  - Unethical battlefield conduct reported by soldiers serving in the Iraq war.
AB  - Research involving military service members has shown a strong relationship
      between combat experiences and increased risk for posttraumatic stress disorder
      (PTSD) and other mental health problems. Comparatively little research has
      examined the relationship between combat experiences, PTSD, aggression, and
      unethical conduct on the battlefield, although news stories sometimes suggest
      links between unethical conduct and disorders such as PTSD. This study
      systematically examined whether unethical conduct is a proxy for aggression and
      whether specific combat experiences and PTSD are independently associated with
      unethical behavior. The results of this study indicate that aggression (beta =
      0.30) and specific combat experiences (particularly, witnessing war atrocities
      [beta = 0.14] and fighting [beta = 0.13]) are much more strongly associated with
      unethical conduct than is PTSD (beta = 0.04).

PMID- 23538968
TI  - Ovarian cancer and DNA repair: DNA ligase IV as a potential key.
AB  - Ovarian cancer (OC) is the sixth most common cancer and the seventh cause of
      death from cancer in women. The etiology and the ovarian carcinogenesis still
      need clarification although ovulation may be determinant due to its carcinogenic
      role in ovarian surface epithelium. The link between ovarian carcinogenesis and
      DNA repair is well established and it became clear that alterations in DNA damage
      response may affect the risk to develop OC. Polymorphisms are variations in the
      DNA sequence that exist in normal individuals of a population and are capable to
      change, among other mechanisms, the balance between DNA damage and cellular
      response. Consequently, genetic variability of the host has a great role in the
      development, progression and consequent prognosis of the oncologic patient as
      well as in treatment response. Standard treatment for OC patients is based on
      cytoreductive surgery, followed by chemotherapy with a platinum agent and a
      taxane. Although 80% of the patients respond to the first-line therapy, the
      development of resistance is common although the mechanisms underlying therapy
      failure remain mostly unknown. Because of their role in oncology, enzymes
      involved in the DNA repair pathways, like DNA Ligase IV (LIG4), became attractive
      study targets. It has been reported that variations in LIG4 activity can lead to
      a hyper-sensitivity to DNA damage, deregulation of repair and apoptosis
      mechanisms, affecting the susceptibility to cancer development and therapy
      response. To overcome resistance mechanisms, several investigations have been
      made and the strategy to target crucial molecular pathways, such as DNA repair,
      became one of the important areas in clinical oncology. This review aims to
      elucidate the link between DNA repair and OC, namely which concerns the role of
      LIG4 enzyme, and how genetic polymorphisms in LIG4 gene can modulate the activity
      of the enzyme and affect the ovarian carcinogenesis and treatment response.
      Moreover, we try to understand how LIG4 inhibition can be a potential contributor
      for the development of new cancer treatment strategies.

PMID- 23538970
TI  - Sexual functioning in patients with recurrent major depressive disorder enrolled
      in the PREVENT study.
AB  - The incidence of treatment-emergent sexual dysfunction in the acute and
      continuation phases of the prevention of recurrent episodes of depression with
      venlafaxine ER for two years (PREVENT) study was assessed. Adult outpatients with
      recurrent major depressive disorder were randomly assigned to receive venlafaxine
      extended release (ER; 75-300 mg/day) or fluoxetine (20-60 mg/day). Sexual
      dysfunction was assessed using items from the 17-item Hamilton Rating Scale for
      Depression (HAM-D(17)) and the Inventory of Depressive Symptomatology-Self-Report
      (IDS-SR). The baseline rates of sexual dysfunction based on the HAM-D(17) and IDS
      SR items were 57.9% and 48.8%, respectively. The rates of new-onset sexual
      dysfunction for the venlafaxine ER-treated (44.8%, HAM-D(17); 38.4%, IDS-SR) and
      fluoxetine-treated patients (52.9%, HAM-D(17); 50.0%, IDS-SR) were similar;
      approximately 80% of the cases resolved during treatment. Treatment response was
      associated with lower rates of new-onset sexual dysfunction compared with
      nonresponse. The patients who remitted were the least likely to experience sexual
      dysfunction during antidepressant treatment.

PMID- 23538971
TI  - Clarifying the relation between spirituality and well-being.
AB  - Koenig (J Nerv Ment Dis 196:349-355, 2008) and others have asserted that measures
      of spirituality used to investigate its association with health seem to present a
      misleading picture of the relationship because of evidence suggesting that
      spirituality has become conceptually confounded with well-being. To evaluate this
      claim, the present study used a sample of 247 university students to explore the
      relation of a multidimensional model of spirituality with several different forms
      of well-being and the association of both with a two-factor model of social
      desirability. Correlational and regression analyses revealed that, although there
      is some evidence of an association, it is generally of low effect size and seems
      to differ as a function of how spirituality is defined. More importantly,
      however, there was the finding that existential well-being, a concept often
      incorporated into definitions of spirituality and a part of the measurement model
      used in this study, is virtually uncorrelated with explicitly spiritual and
      religious variables but shows a pattern of association with measures of well
      being and social desirability, which suggests that it would be better
      conceptualized as a form of well-being and not spirituality. The article
      concludes with a discussion of the meaning of the findings for understanding the
      spirituality-health literature and suggestions for future research.

PMID- 23538972
TI  - Stigmatizing attitudes differ across mental health disorders: a comparison of
      stigma across eating disorders, obesity, and major depressive disorder.
AB  - The aim of the current article was to compare stigmatizing attitudes toward
      eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN),
      and binge eating disorder (BED), with stigma toward another weight-related
      condition (obesity) and a non-weight-related mental disorder (major depressive
      disorder [MDD]). Participants (N = 447) read five vignettes describing a woman
      with AN, BN, BED, obesity, or MDD and responded to questionnaires examining
      stigmatizing attitudes. The targets with EDs were blamed more for their condition
      than the targets with MDD, whereas persons with obesity were held more
      responsible for their condition than any other target. On the other hand, the
      target with MDD was perceived as more impaired than any other target. Lack of
      self-discipline was attributed more to the development of BED and obesity than to
      any other condition. Stigmatizing attitudes vary across mental health disorders,
      and future research should aim to specifically target stigmatizing beliefs to
      reduce and prevent discrimination toward mental health disorders and obesity.

PMID- 23538973
TI  - Permissive attitude toward suicide and future intent in individuals with and
      without depression: results from a nationwide survey in Korea.
AB  - Many previous studies have revealed that individuals with depression have higher
      thought of suicide, although not always exhibiting intent. We investigated the
      associated factors with respect to intent for suicide in the future. A total of
      1584 adults were selected through a nationwide multistage probability sampling,
      randomly one person per household, and through face-to-face interviews (response
      rate was 63.4%) using the suicidality module of the Mini-International
      Neuropsychiatric Interview and the Patient Health Questionnaire-9. The group with
      depression (n = 152) revealed a significantly higher level of future suicide
      intent (t = 4.65, p <0.0001) and permissive attitude (t = 4.32, p <0.0001) than
      did the group without depression, which regarded suicide as free from life
      suffering, a personal right, and a solution to a difficult situation. After
      adjusting for all variables in the multiple logistic regression models,
      permissive attitude (adjusted odds ratio, 3.69; 95% confidence interval, 1.97
      6.89) was the only factor significantly associated with future suicide intent,
      whereas age; sex; education years; monthly income; financial, job, and family
      stress; physical illness; lifetime suicide attempt; and depression showed no
      statistical significance. The group with depression showed significantly higher
      levels of future suicide intent than did the group without depression in those
      who had a higher permissive attitude (t = 4.18, p <0.0001) but not in those who
      had lower permissive attitudes (t = 1.98, p = 0.067). Permissive attitude toward
      suicide was associated with intent for suicide in the future in individuals with
      depression. Permissive attitude could be evaluated and corrected to prevent
      suicide.

PMID- 23538974
TI  - Distress, coping, and drug law enforcement in a series of patients using medical
      cannabis.
AB  - Patients using medical cannabis in the United States inhabit a conflicting
      medicolegal space. This study presents data from a dispensary-based survey of
      patients using medical cannabis in the state of Washington regarding cannabis
      specific health behaviors, levels of psychological distress, stress regarding
      marijuana criminality, past experiences with drug law enforcement, and coping
      behaviors. Thirty-seven subjects were enrolled in this study, and all but three
      completed survey materials. The median index of psychological distress, as
      measured by the Behavioral Symptom Inventory, was nearly 2.5 times higher than
      that found in a general population sample but one third less than that found in
      an outpatient sample. The subjects reported a moderate amount of stress related
      to the criminality of marijuana, with 76% reporting previous exposure to 119
      separate drug law enforcement tactics in total. The subjects reported a wide
      range of coping methods, and their responses to a modified standardized survey
      showed the confounding influence of legality in assessing substance-related
      disorders.

PMID- 23538975
TI  - Emotion regulation and mental representation of attachment in patients with
      systemic lupus erythematosus: a study using the Adult Attachment Interview.
AB  - Mental representations of attachment and emotion regulation influence individual
      patterns of stress response and vulnerability to illness. The present study
      investigates the adult attachment states of mind of 40 women with systemic lupus
      erythematosus (SLE) using the Adult Attachment Interview. We also assessed
      alexithymia using the Toronto Alexithymia Scale and dissociation using the
      Dissociative Experiences Scale. The results showed a high prevalence of the
      unresolved state of mind (13 patients, 32.5%) and the entangled state of mind (10
      patients, 25%). The alexithymia score also varied significantly as a function of
      the mental representation of attachment and was modulated by amnestic
      dissociation. These findings suggest that adult attachment in patients with SLE
      influences the presence of alexithymic features. Moreover, these also indicate
      that dissociative states mediate the perception of painful memories and feelings,
      thus contributing to the partial avoidance of emotions and the failure to fully
      experience and recognize them. The clinical implications of these findings are
      also discussed.

PMID- 23538976
TI  - Beliefs and attitudes among Italian high school students toward people with
      severe mental disorders.
AB  - The negative attitudes surrounding mental disorders and their treatment are a
      major obstacle to the correct identification and treatment of emerging
      psychopathologies. The purpose of this study was to investigate mental health
      literacy in a large and representative sample of high school students in Italy,
      via a booklet containing several questionnaires delivered to 1032 teenagers. The
      items in the questionnaires probed knowledge about mental health and illness,
      stigmatization, stereotypes, behaviors, opinions, and attitudes. In general, the
      students had a reasonable knowledge of mental disorders and were able to
      distinguish these from somatic disorders. However, a large portion of the
      students nourished some misconceptions about mental disorders and was also rather
      skeptical about the effectiveness of treatment or the chance of recovery for
      people with severe mental disorders. Nevertheless, roughly half of the students
      reported being willing to provide help to someone with a mental disorder when in
      need. Poor mental health literacy is a major barrier to seeking help and
      receiving effective treatment. Young people are the ideal target of raising
      awareness and antistigma campaigns because they are at a higher risk for
      developing a psychopathology.

PMID- 23538977
TI  - Illusory correlations and control across the psychosis continuum: the
      contribution of hypersalient evidence-hypothesis matches.
AB  - It has recently been proposed that individuals with delusions may be hypersalient
      to evidence-hypothesis matches, which may contribute to the formation and the
      maintenance of delusions. However, empirical support for the construct is
      limited. Using cognitive tasks designed to elicit the illusory correlation bias
      (i.e., perception of a correlation in which none actually exists) and the
      illusion of control bias (i.e., overestimation of one's personal influence over
      an outcome), the current article investigates the possibility that individuals
      with delusions are hypersalient to evidence-hypothesis matches. It was
      hypothesized that this hypersalience may increase a person's propensity to rely
      on such illusory correlations and estimates of control. A total of 75
      participants (25 participants diagnosed with schizophrenia with a history of
      delusions, 25 nonclinical participants with delusion proneness, and 25 controls
      without delusion proneness) completed computerized versions of the "fertilizer"
      illusory correlation task developed by Kao and Wasserman (J Exp Psychol Learn Mem
      Cogn 19:1363-1386; 1993) and the "light-onset" illusion of control task created
      by Alloy and Abramson (J Exp Psychol Gen 108:441-485; 1979). The results across
      both tasks showed that the participants with schizophrenia were more susceptible
      than the nonclinical groups to illusory correlations (i.e., higher estimates of
      covariation between unrelated events) and illusions of control (i.e., higher
      estimates of control and perceived connection between the responses and the
      outcome). These results suggest that delusional ideation is linked to a
      hypersalience of evidence-hypothesis matches. The theoretical implications of
      this cognitive mechanism on the formation and the maintenance of delusions are
      discussed.

PMID- 23538978
TI  - Persistence of symptoms in primary somatoform vertigo and dizziness: a disorder
      "lost" in health care?
AB  - The aim of this study was to perform a 3-year follow-up of primary somatoform
      vertigo and dizziness (SVD) regarding health care use and treatment. Ninety-two
      patients with dizziness underwent detailed vestibular neurophysiological testing
      and a Structured Clinical Interview for Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition. Psychometric assessments comprised the Vertigo
      Symptom Scale, the Vertigo Handicap Questionnaire, the SCL-90-R, and the Short
      Form-36 Health Survey. At the 3-year follow-up, 65 patients with primary SVD
      (anxiety, n = 29; depression, n = 14; somatoform disorders, n = 22) were
      reassessed (70.7% response). The patients improved in symptom severity (p <
      0.05), handicap (p < 0.01), and physical quality of life (QoL; p < 0.05) but
      showed no change in emotional distress. A total of 63.1% (of n = 65) had ongoing
      SVD. A total of 69.2% (of n = 65) received different forms of treatments. A total
      of 46.1% (of n = 65) searched redundant medical diagnostic procedures. The
      patients with decreased coping capacity over time obtained the best prognosis.
      Primary SVD is an ineffectively treated disorder. Recommendations for specific
      complaint-oriented psychotherapy programs were given.

PMID- 23538979
TI  - Quality of life and marital adjustment in remitted psychiatric illness: an
      exploratory study in a rural setting.
AB  - People with mental disorders experience impaired quality of life (QOL). In India,
      spouses form the most important caregiver for the patient and therefore impact
      the patients' QOL. However, relatively little is known about marital adjustment,
      which can definitely influence QOL of patients with mental illness. This study
      intended to explore marital adjustment and QOL among remitted patients with
      schizophrenia (SC), depression, and bipolar disorders (BPADs) and to study
      differences, if any, between the groups. Using a cross-sectional design,
      consecutive patients (N = 150) with an ICD-10-Diagnostic Criteria for Research
      diagnosis of SC, depression (recurrent depressive disorder [RDD]), or BPAD, who
      were currently in remission, were taken up for the study and administered the
      WHOQOL-BREF for assessing QOL and the Marital Adjustment Inventory for assessing
      marital adjustment, separately for the husband and the wife. The patients with SC
      reported poor QOL, whereas a better QOL was seen in those with BPAD and RDD, with
      significant differences noted between all three groups (p < 0.001). Marital
      adjustment was perceived to be poor by the patients but not so by the spouses.
      The greatest marital dissatisfaction was reported by the patients with SC (96%).
      A positive correlation was observed between the patients' perception of marital
      adjustment and QOL (p < 0.05). Provision of mental health care should take into
      consideration patients' possible perception of marital maladjustment and factor
      these into treatment strategies.

PMID- 23538980
TI  - Levels of patient activation among adults with schizophrenia: associations with
      hope, symptoms, medication adherence, and recovery attitudes.
AB  - Patient activation, defined as one's attitudes and confidence toward managing
      illness, has been not been thoroughly studied in consumers with schizophrenia.
      The current study sought to understand the relationship between patient
      activation and symptoms, medication adherence, recovery attitudes, and hope in a
      sample of 119 adults with schizophrenia. The participants were enrolled in an 18
      month randomized controlled study of the Illness Management and Recovery program.
      Data were collected at baseline; correlations and stepwise multiple regressions
      were used to examine the relationships and determine the unique contribution of
      variables. Higher patient activation was most strongly associated with positive
      recovery attitudes, higher levels of hope, and fewer emotional discomfort
      symptoms. Patient activation was significantly related to a broad measure of
      illness self-management, providing evidence for the construct validity of the
      patient activation measure. Our findings emphasize the importance of recovery
      based mental health services that recognize level of patient activation as a
      potential factor in consumer outcomes.

PMID- 23538981
TI  - Consenting not to be informed: a survey on the acceptability of placebo use in
      the treatment of depression.
AB  - The aim of this study was to investigate the opinions of healthy students
      regarding the acceptability of placebo treatment if they were to experience
      depression. A survey was conducted among 344 students in five academic centers in
      Israel. After a thorough explanation of the placebo effect, its efficacy and
      limitations in the treatment of depression, the study participants completed a 32
      item self-report questionnaire. Seventy percent (n = 243) of the participants
      answered that they would agree to treatment with a placebo as a first-line
      treatment if they were to experience depression in the future. Eighty-eight
      percent (n = 297) of the subjects did not think that a physician who administered
      placebos was deceitful. Once aware of the possible benefits and limitations of
      placebo treatment, most of our study population was willing to accept placebo as
      a legitimate treatment of depression. Additional studies on the possible use of
      placebo as an effective, safe, and acceptable form of therapy are warranted.

PMID- 23538983
TI  - Growing not dwindling: international research on the worldwide phenomenon of
      dissociative disorders.

PMID- 23538982
TI  - Prevalence of childhood physical and sexual abuse in veterans with psychiatric
      diagnoses.
AB  - We examined the prevalence of childhood (<= 18 years) physical and sexual abuse
      reported among patients admitted to the psychiatric inpatient service and the
      differential rates of this abuse associated with psychiatric diagnoses. This
      study consisted of a retrospective chart review of 603 patients admitted to a
      psychiatric ward during a period of 1 year at Atlanta Veterans Affairs Medical
      Center who had data on childhood physical and sexual abuse. The prevalence of
      reported childhood physical or sexual abuse in this inpatient clinical population
      was 19.4% (117/603). The prevalence of reported physical abuse was 22.6% (19/84)
      in the women and 12.0% (62/519) in the men (p = 0.008); the prevalence of sexual
      abuse was 33.3% (28/84) in the women and 7.7% (40/519) in the men (p < 0.0001).
      More patients with depressive disorders reported sexual abuse than did those
      without these disorders. More patients with posttraumatic stress disorder (PTSD)
      reported physical and sexual abuse than did those without these disorders.
      Stratifying by race, sex, and diagnoses, multivariate analyses showed that the
      women with PTSD had a greater likelihood to report physical abuse (p = 0.03) and
      sexual abuse histories (p = 0.008) than did the women without PTSD. The men with
      substance-induced mood disorder (p = 0.01) were more likely to report physical
      abuse compared with the men without substance-induced mood disorder. Screening
      for abuse in patients with depressive disorders and PTSD is warranted to tailor
      individualized treatments for these patients. More research is needed to better
      understand the potential implications of childhood abuse on psychiatric
      diagnoses.

PMID- 23538984
TI  - Disinformation about dissociation: Dr Joel Paris's notions about dissociative
      identity disorder.

PMID- 23538985
TI  - Response to dissociative identity disorder letters from Martinez-Taboas et al.
      and Brand et al.

PMID- 23538986
TI  - Do fads ever die?

PMID- 23538987
TI  - Cardiorespiratory fitness in breast cancer survivors.
AB  - Maximal oxygen uptake (VO2max) has been used to assess risk for all-cause
      mortality and cardiovascular disease (CVD), and low VO2max has recently been
      associated with increased mortality from breast cancer. The purpose of this study
      was to determine the proportion of breast cancer survivors with 2 or more risk
      factors for CVD exhibiting a low VO2max and to determine whether sub-maximal
      endpoints which could be applied more readily to intervention research would
      correlate with the maximal treadmill test. We performed a single VO2max test on a
      treadmill with 30 breast cancer survivors age 30-60 (mean age 50.5 +/- 5.6 years)
      who had 2 or more cardiac risk factors for CVD not related to treatment and who
      had received systemic therapy and or left chest radiation. Submaximal VO2
      endpoints were assessed during the VO2max treadmill test and on an Arc trainer.
      Resting left ventricular ejection fraction (LVEF) was also assessed by
      echocardiogram (ECHO) or multi-gated acquisition scan (MUGA). A majority (23/30)
      of women had a VO2max below the 20th percentile based on their predicted normal
      values. The group mean resting LVEF was 60.5 +/- 5.0%. Submaximal VO2 measures
      were strongly correlated with the maximal test including; 1) 85% age predicted
      maximum heart rate VO2 on treadmill, (r = .89; p < 0.001), 2) treadmill VO2 at
      anaerobic threshold (AT), (r = .83; p < 0.001), and 3) Arc VO2 at AT, (r = .80; p
      < 0.001). Breast cancer survivors with 2 or more CVD risk factors but normal LVEF
      had a low cardiorespiratory fitness level compared to normative values in the
      healthy population placing them at increased risk for breast cancer and
      cardiovascular mortality. Submaximal VO2 exercise testing endpoints showed a
      strong correlation with the VO2max test in breast cancer survivors and is a good
      candidate for testing interventions to improve cardiorespiratory fitness. 

PMID- 23538988
TI  - Effect of autotransfusion system on tumor recurrence and survival in
      hepatocellular carcinoma patients.
AB  - AIM: To investigate the therapeutic efficacy and safety of continuous
      autotransfusion system (CATS) during liver transplantation of hepatocellular
      carcinoma patients. METHODS: Eighty-three hepatocellular carcinoma (HCC) patients
      who underwent liver transplantation with intraoperative CATS (n = 24, CATS group)
      and without (n = 59, non-CATS group) between April 2006 and November 2011 at the
      Liver Transplant Institute of Inonu University were analyzed retrospectively.
      Postoperative HCC recurrence was monitored by measuring alpha-fetoprotein (AFP)
      levels at 3-mo intervals and performing imaging analysis by thoracoabdominal
      multidetector computed tomography at 6-month intervals. Inter-group differences
      in recurrence and correlations between demographic, clinical, and pathological
      data were assessed by ANOVA and chi(2) tests. Overall and disease-free survivals
      were calculated by the univariate Kaplan-Meier method. RESULTS: Of the 83 liver
      transplanted HCC patients, 89.2% were male and the overall mean age was 51.3 +/-
      8.9 years (range: 18-69 years). The CATS and non-CATS groups showed no
      statistically significant differences in age, sex ratio, body mass index,
      underlying disease, donor type, graft-to-recipient weight ratio, Child-Pugh and
      Model for End-Stage Liver Disease scores, number of tumors, tumor size, AFP
      level, Milan and University of California San Francisco selection criteria, tumor
      differentiation, macrovascular invasion, median hospital stay, recurrence rate,
      recurrence site, or mortality rate. The mean follow-up time of the non-CATS group
      was 17.9 +/- 12.8 mo, during which systemic metastasis and/or locoregional
      recurrence developed in 25.4% of the patients. The mean follow-up time for the
      CATS group was 25.8 +/- 15.1 mo, during which systemic metastasis and/or
      locoregional recurrence was detected in 29.2% of the patients. There was no
      significant difference between the CATS and non-CATS groups in recurrence rate or
      site. Additionally, no significant differences existed between the groups in
      overall or disease-free survival. CONCLUSION: CATS is a safe procedure and may
      decrease the risk of tumor recurrence in HCC patients.

PMID- 23538989
TI  - Enhancing the Cellular Delivery of Nanoparticles using Lipo-Oligoarginine
      Peptides.
AB  - Nanoparticles have great potential as nanotherapeutics, delivery vectors, and
      molecular imaging agents due to their flexible properties. Although intracellular
      and nuclear delivery of nanoparticles is desirable for therapeutic applications,
      it remains a challenge. Cell penetrating peptides (CPPs) are a powerful tool for
      the intracellular delivery of various cargoes. Here we report that
      functionalization of nanoparticles with a myristoylated oligoarginine CPP
      promoted cellular uptake without increased toxicity. It was evidenced that the
      myristoylated CPP is much more effective in transporting nanoparticles than the
      unmodified CPPs.

PMID- 23538990
TI  - Rapid facial mimicry in geladas.
AB  - Rapid facial mimicry (RFM) is an automatic response, in which individuals mimic
      others' expressions. RFM, only demonstrated in humans and apes, is grounded in
      the automatic perception-action coupling of sensorimotor information occurring in
      the mirror neuron system. In humans, RFM seems to reflect the capacity of
      individuals to empathize with others. Here, we demonstrated that, during play,
      RFM is also present in a cercopithecoid species (Theropithecus gelada). Mother
      infant play sessions were not only characterized by the highest levels of RFM,
      but also by the fastest responses. Our findings suggest that RFM in humans have
      homologous not only in apes, but also in cercopitecoids. Moreover, data point to
      similarities in the modality in which mother-infant synchronous behaviours are
      expressed among primates, suggesting a common evolutionary root in the basic
      elements of mother-infant affective exchanges.

PMID- 23538991
TI  - The complete chloroplast genome sequence of Cephalotaxus oliveri
      (Cephalotaxaceae): evolutionary comparison of cephalotaxus chloroplast DNAs and
      insights into the loss of inverted repeat copies in gymnosperms.
AB  - We have determined the complete chloroplast (cp) genome sequence of Cephalotaxus
      oliveri. The genome is 134,337 bp in length, encodes 113 genes, and lacks
      inverted repeat (IR) regions. Genome-wide mutational dynamics have been
      investigated through comparative analysis of the cp genomes of C. oliveri and C.
      wilsoniana. Gene order transformation analyses indicate that when distinct
      isomers are considered as alternative structures for the ancestral cp genome of
      cupressophyte and Pinaceae lineages, it is not possible to distinguish between
      hypotheses favoring retention of the same IR region in cupressophyte and Pinaceae
      cp genomes from a hypothesis proposing independent loss of IRA and IRB.
      Furthermore, in cupressophyte cp genomes, the highly reduced IRs are replaced by
      short repeats that have the potential to mediate homologous recombination,
      analogous to the situation in Pinaceae. The importance of repeats in the
      mutational dynamics of cupressophyte cp genomes is also illustrated by the accD
      reading frame, which has undergone extreme length expansion in cupressophytes.
      This has been caused by a large insertion comprising multiple repeat sequences.
      Overall, we find that the distribution of repeats, indels, and substitutions is
      significantly correlated in Cephalotaxus cp genomes, consistent with a hypothesis
      that repeats play a role in inducing substitutions and indels in conifer cp
      genomes.

PMID- 23538993
TI  - Endovascular management of pulmonary artery stenosis due to tumor compression.
AB  - A 75-year-old man with invasive thymoma encasing the aortic arch and pulmonary
      arteries was referred to our institution with a 1-year history of dyspnea and
      worsening right heart failure. Pulmonary angiogram demonstrated greater than 90%
      stenosis of the right pulmonary artery. Balloon angioplasty and stent placement
      were performed with immediate improvement in his shortness of breath and
      peripheral edema. Improved lung opacification was noted on completion
      arteriography, and the stents remained patent until the patient expired from
      complications related to his cancer 2 years later. Pulmonary artery stenting in
      noncongenital causes of stenosis is a safe and effective therapy.

PMID- 23538992
TI  - Comparative genomic analysis of rapid evolution of an extreme-drug-resistant
      Acinetobacter baumannii clone.
AB  - The emergence of extreme-drug-resistant (EDR) bacterial strains in hospital and
      nonhospital clinical settings is a big and growing public health threat.
      Understanding the antibiotic resistance mechanisms at the genomic levels can
      facilitate the development of next-generation agents. Here, comparative genomics
      has been employed to analyze the rapid evolution of an EDR Acinetobacter
      baumannii clone from the intensive care unit (ICU) of Rigshospitalet at
      Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were
      sequentially isolated from two individuals who had been admitted to ICU within a
      1-month interval. Multilocus sequence typing indicates that these two isolates
      belonged to ST208. The A. baumannii 53264 strain gained colistin resistance
      compared with the 48055 strain and became an EDR strain. Genome sequencing
      indicates that A. baumannii 53264 and 48055 have almost identical genomes-61
      single-nucleotide polymorphisms (SNPs) were found between them. The A. baumannii
      53264 strain was assembled into 130 contigs, with a total length of 3,976,592 bp
      with 38.93% GC content. The A. baumannii 48055 strain was assembled into 135
      contigs, with a total length of 4,049,562 bp with 39.00% GC content. Genome
      comparisons showed that this A. baumannii clone is classified as an International
      clone II strain and has 94% synteny with the A. baumannii ACICU strain. The
      ResFinder server identified a total of 14 antibiotic resistance genes in the A.
      baumannii clone. Proteomic analyses revealed that a putative porin protein was
      down-regulated when A. baumannii 53264 was exposed to antimicrobials, which may
      reduce the entry of antibiotics into the bacterial cell.

PMID- 23538994
TI  - Endovascular treatment of an iatrogenic vertebrojugular fistula with a balloon
      expandable covered stent: case report and review of the literature.
AB  - We report a case of a fistula between the vertebral artery and the internal
      jugular vein that occurred after the erroneous placement of a central venous
      catheter. The patient was presented with tinnitus. Endovascular treatment with a
      balloon expandable covered stent placed into the vertebral artery was performed.
      One year follow-up showed satisfactory exclusion of the fistula, patency of the
      stented vertebral artery, and resolution of the symptoms. Only few other similar
      cases are reported in the literature with the use of different types of stents.

PMID- 23538995
TI  - Laparoscopic sacropexy and obstructed defecation syndrome: an anatomoclinical
      study.
AB  - INTRODUCTION AND HYPOTHESIS: Laparoscopic sacropexy (LSP) is associated with
      obstructed defecation syndrome (ODS) in 10-50% of cases. An anatomoclinical study
      was carried out to investigate whether there is any correlation between
      iatrogenic denervation during LSP and ODS. METHODS: Five female cadavers were
      dissected to identify possible sites of nerve injury during LSP. Subsequently,
      the videos of 18 LSP were blindly reviewed to assess the location of sacral
      dissection and tacks, the position and depth of the peritoneal tunnel, and
      another 4 variables. An anatomical triangle was defined on the right lumbosacral
      spine so as to clearly describe the sites of the surgical variables, which were
      then statistically correlated with the patients' postoperative outcome. RESULTS:
      The only variable associated with postsurgical ODS was dissection in the 90
      degrees  angle of the anatomical triangle, where the superior hypogastric plexus
      was observed in all cadavers. CONCLUSIONS: Medial and midline dissection over the
      sacral promontory might be associated with postoperative ODS.

PMID- 23538997
TI  - [Tumor boards: why they are necessary and which structure is needed].
AB  - This review article gives a detailed overview regarding the growing importance of
      tumor boards in the daily clinical life. Improved diagnostic and therapeutic
      options for oncologic diseases lead to an increased complexity in patient
      management, which can only be handled optimally by a team of specialists. Within
      this process radiology as a specialty is of growing importance and constitutes
      the core in the diagnostic algorithm. Radiology is necessary for optimal tumor
      staging. In summary, there is a growing importance of tumor boards in the
      management of oncologic diseases and radiologists are a key factor in this
      process.

PMID- 23538996
TI  - Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for
      predicting anemia in Egyptian hepatitis C virus patients.
AB  - AIM: To investigate and clarify, for the first time, the role of inosine
      triphosphate pyrophosphatase (ITPA) polymorphism in Egyptian chronic hepatitis C
      virus (HCV) patients. METHODS: The human genomic DNA of all patients was
      extracted from peripheral blood cells in order to determine the single nucleotide
      polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time
      polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102
      treatment-naive Egyptian patients with chronic HCV. All patients had no evidence
      of cardiovascular or renal diseases. They received a combination treatment of
      pegylated interferon alpha (PEG-IFNalpha) as a weekly subcutaneous dose plus an
      oral weight-adjusted dose of ribavirin (RBV). The majority received PEG
      IFNalpha2a (70.6%) while 29.4% received PEG-IFNalpha2b. The planned duration of
      treatment was 24-48 wk according to the viral kinetics throughout the course of
      treatment. Pre-treatment liver biopsy was done for each patient for evaluation of
      fibrosis stage and liver disease activity. The basal viral load level was
      detected quantitatively by real time PCR while viral load throughout the
      treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS:
      Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC
      genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC
      patients than for non-CC patients, particularly at weeks 4 and 8 (P = 0.047 and
      0.034, respectively). During the first 12 wk of treatment, CC patients had
      significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at
      weeks 8 and 12, respectively, (P = 0.024 and 0.038). Reduction of the amount of
      the planned RBV dose was significantly higher for CC patients than non-CC
      patients during the first 12 wk (18% +/- 12.1% vs 8.5% +/- 10.2%, P = 0.021). The
      percentage of CC patients with RBV dose reduction was significantly greater than
      that of non-CC patients (77.4% vs 44.4%, P = 0.044). Multivariate analysis
      identified only the percentage of RBV dose as a predictor for Hb decline.
      Platelet decline was significantly higher in non-CC patients than CC patients at
      weeks 12, 24 and 48 (P = 0.018, 0.009 and 0.026, respectively). CONCLUSION:
      Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment
      induced anemia and the need for RBV dose reduction in Egyptian HCV patients.

PMID- 23538998
TI  - A simple and versatile microfluidic cell density gradient generator for quantum
      dot cytotoxicity assay.
AB  - In this work, a simple and versatile microfluidic cell density gradient generator
      was successfully developed for cytotoxicity of quantum dots (QDs) assay. The
      microfluidic cell density gradient generator is composed of eight parallel
      channels which are respectively surrounded by 1-8 microwells with optimized
      length and width. The cells fall into microwells by gravity and the cell
      densities are obviously dependent of microwell number. In a case study, HepG2 and
      MCF-7 cells were successfully utilized for generating cell density gradients on
      the microfluidic chip. The microfluidic cell density gradient generator was
      proved to be easily handled, cell-friendly and could be used to conduct the
      subsequent cell-based assay. As a proof-of-concept, QD cytotoxicity was evaluated
      and the results exhibited obvious cell density-dependence. For comparison, QD
      cytotoxicity was also investigated with a series of cell densities infused by
      pipette tips. Higher reproducibility was observed on the microfluidic cell
      density gradient generator and cell density was demonstrated to be a vital factor
      in cytotoxic study. With higher efficiency, controllability and reproducibility,
      the microfluidic cell density gradient generator could be integrated into
      microfluidic analysis systems to promote chip-based biological assay.

PMID- 23538999
TI  - Paraneoplastic cutaneous manifestations: concepts and updates.
AB  - The skin often signals systemic changes. Some neoplastic diseases that affect
      internal organs may trigger several cutaneous manifestations. Although these
      dermatoses are relatively unusual, the recognition of some typical paraneoplastic
      dermatoses may lead to the early diagnosis of a neoplasm and determine a better
      prognosis. In this review article, we discuss the paraneoplastic cutaneous
      manifestations strongly associated with neoplasms, which include acanthosis
      nigricans maligna, tripe palms, erythema gyratum repens, Bazex syndrome, acquired
      hypertrichosis lanuginosa, necrolytic migratory erythema, Leser-Trelat sign and
      paraneoplastic pemphigus. We also review the clinical manifestations of each
      condition and include updated knowledge on disease pathogenesis.

PMID- 23539000
TI  - Analysis of interobserver reproducibility in grading histological patterns of
      dysplastic nevi.
AB  - BACKGROUND: Dysplastic nevi are among the most important cutaneous melanoma
      simulators. They are important risk markers for this neoplasia and can be its
      potential precursors. Some authors found a statistically significant relationship
      between the degree of dysplasia and the risk for developing melanoma. However,
      reproducibility of grading criteria ranged from poor to fair in the researched
      articles. OBJECTIVE: To test the reproducibility of the grading criteria proposed
      by Sagebiel et al. regarding dysplastic nevi. METHODS: Histological specimens of
      75 dysplastic nevi were graded, independently and in a blinded fashion, according
      to preestablished criteria, by a panel of 10 pathologists with different levels
      of experience. Diagnostic agreement was calculated using weighted kappa and
      intraclass correlation coefficients. RESULTS: The average of weighted kappa
      values was 0.13 for all observers, 0.12 for dermatopathologists, 0.18 for general
      pathologists and 0.05 for residents. Intraclass correlation coefficient values
      were 0.2 for all observers, 0.18 for dermatopathologists, 0.33 for general
      pathologists and 0.15 for residents. CONCLUSIONS: Histopathological grading for
      dysplastic nevi was not reproducible in this Brazilian series, so the criteria
      used are not a helpful histopathological parameter for clinicopathological
      correlation.

PMID- 23539001
TI  - Histopathological and immunohistochemical aspects of American cutaneous
      leishmaniasis before and after different treatments.
AB  - BACKGROUND: The histopathology and immune responses of the healing process of
      leishmaniasis are still poorly studied. OBJECTIVES: This study aimed to examine
      the histopathological and immunological aspects of lesions of patients with
      cutaneous leishmaniasis before and after different therapeutic methods. METHODS:
      We studied 23 individuals grouped according to the treatments: Glucantime,
      Glucantime + Leishvacin and Glucantime + Leishvacin associated with Bacillus
      Calmette-Guerin. For analysis of the histopathological changes present in the
      dermis and epidermis, histological sections were stained with hematoxylin and
      eosin. The samples were immunostained before and after treatment to analyze the
      expression of interferon (IFN)-gamma, interleukin (IL) 12, IL-10 and IL-4.
      RESULTS: Before treatment the presence of intense infiltrates of mononuclear
      cells was noticed and after treatment, even with a diagnosis of clinical cure,
      the subjects still showed a moderate inflammatory process. In the
      immunohistochemical analyses, we noticed a difference between the cytokines, with
      increased expression of cytokines IFN-gamma and IL-12 compared to IL 10 and IL-4,
      both before and after treatment and, comparatively, the difference in this
      expression was more intense before treatment. However, the cytokine expression
      analyzed by treatment group showed no statistically significant difference.
      CONCLUSION: We conclude that a clinical cure does not always coincide with the
      histopathological one, and that before treatment there is a predominance of Th1
      cytokines. In terms of treatment type, there was no difference in the progression
      of healing for all the three types of treatment, indicating their clinical
      equivalence.

PMID- 23539002
TI  - Evaluating the effectiveness of the customized Unna boot when treating patients
      with venous ulcers.
AB  - BACKGROUND: Lower limb ulcers are a serious medical and socioeconomic problem
      throughout the world. One type of chronic wound of the lower extremities is the
      venous ulcer. Therapeutic methods for treating venous ulcer include the use of
      the Unna boot. OBJECTIVES: To evaluate the effectiveness of the customized Unna
      boot in the treatment of venous ulcers and to monitor the subsequent development
      and healing of the lesions. METHODS: Prospective exploratory and quantitative
      longitudinal study, conducted at the "Outpatients Department (Wound Care) of the
      Grupo da Fraternidade Espirita Irmao Alexandre" in the city of Pouso Alegre (MG),
      Brazil, in 2008. The sample consisted of 32 patients with venous ulcers who
      underwent treatment with the Unna boot and 11 patients (control group), who used
      a simple bandage application. The patients'lesions were monitored over a three
      month period. RESULTS: The average age of the predominently female (65.1%)
      patients was 61.88. From observing the differences in healing times at the three
      evaluation stages, it was clear that after the initial evaluation the wound area
      decreased in Groups 1 and 2 (p>0.05). CONCLUSION: The use of the customized Unna
      boot contributes to quicker healing. However, over a period of three months the
      simple bandage applications were seen to be just as effective as the Unna boot
      method.

PMID- 23539003
TI  - Low level laser therapy (AlGaInP) applied at 5J/cm2 reduces the proliferation of
      Staphylococcus aureus MRSA in infected wounds and intact skin of rats.
AB  - BACKGROUND: Laser therapy is a low cost, non-invasive procedure with good healing
      results. Doubts exist as to whether laser therapy action on microorganisms can
      justify research aimed at investigating its possible effects on bacteria-infected
      wounds. OBJECTIVE: To assess the effect of low intensity laser on the rate of
      bacterial contamination in infected wounds in the skin of rats. METHODS: An
      experimental study using 56 male Wistar rats. The animals were randomly divided
      into eight groups of seven each. Those in the "infected" groups were infected by
      Staphylococcus aureus MRSA in the dorsal region. Red laser diode (AlGaInP) 658nm,
      5J/cm2 was used to treat the animals in the "treated" groups in scan for 3
      consecutive days. Samples were drawn before inoculating bacteria and following
      laser treatment. For statistical analysis we used the nonparametric Wilcoxon
      (paired data) method with a significance level of p <0.05. RESULTS: The
      statistical analysis of median values showed that the groups submitted to laser
      treatment had low bacterial proliferation. CONCLUSION: The laser (AlGaInP), with
      a dose of 5J/cm2 in both intact skin and in wounds of rats infected with
      Staphylococcus aureus MRSA, is shown to reduce bacterial proliferation.

PMID- 23539004
TI  - Prevalence of lip and perioral Ephelides in beach workers.
AB  - BACKGROUND: Ephelides are small hyperpigmented macules common in the skin,
      presenting as areas with increased melanin production. Ephelides are observed in
      genetically predisposed individuals, particularly fair-skinned people highly
      susceptible to sunburn. OBJECTIVES: This study aimed to determine the prevalence
      of lip and perioral ephelides in 362 beach workers in the city of Natal (Rio
      Grande do Norte) and to investigate potential associations with sociodemographic,
      occupational and general health. METHODS: For this purpose clinical tests were
      performed by calibrated examiners in the epidemiological area around the lips and
      the area bounded laterally by the nasolabial groove and at the bottom by the
      chin. A questionnaire was completed and assessed. The possible associations
      between sociodemographic variables, occupational and general health with the
      presence of lip and perioral ephelides were evaluated by chi-square test for a
      significance level of 5%. RESULTS: Approximately one third of the workers were
      affected by perioral ephelides (33.7%) and around a quarter of them by lip
      ephelides (24.0%). Gender was the only variable significantly associated with the
      presence of perioral ephelides (p = 0.002), unlike lip ephelides which proved to
      be significantly associated with habits (p = 0.036) and alcoholism (0.030).
      CONCLUSIONS: The prevalence of ephelides in lip and perioral region was high in
      the study population, with gender and certain habits associated with its
      occurrence.

PMID- 23539005
TI  - Prevalence of weathering nodules of the ear in patients treated at the state
      civil servant's hospital of Sao Paulo, Brazil.
AB  - BACKGROUND: Weathering nodules of the ear are pale yellow, asymptomatic lesions
      which predominate on the helices of the ears. Although their pathogenesis remains
      unknown, there is an association with chronic exposure to ultraviolet radiation,
      age and thermal injuries. Few studies have been conducted to date, and these
      involved a very small number of patients. OBJECTIVE: Study the prevalence of
      weathering nodules of the ear in patients treated in the Dermatology Service of
      the State Civil Servant's Hospital of Sao Paulo, and evaluate their probable
      relationship with sun exposure, age and phototypes I and II. METHODS: Four
      hundred patients older than 20 years of age were examined between July 2008 and
      December 2008. A questionnaire evaluating age, sex, place of birth, origin,
      occupation and history of sun exposure was applied. All patients were examined
      and evaluated for the presence of lesions by only one person. RESULTS: The data
      showed that 155 (38.8%) patients had a lesion in at least one of the ears. The
      Chi-Square Test was used for the comparative analysis between the groups of
      patients with and without lesions. In the group of patients with lesions, 29%
      were 70 to 79 years old, 78.1% had a history of sun exposure and 45.1% belonged
      to FITZPATRICK skin phototypes I and II (p<0.05%). CONCLUSION: The findings
      suggest relevant prevalence, probable association with chronic sun exposure,
      advanced age and phototypes I and II.

PMID- 23539006
TI  - How to design and write a clinical research protocol in Cosmetic Dermatology.
AB  - Cosmetic Dermatology is a growing subspecialty. High-quality basic science
      studies have been published; however, few double-blind, randomized controlled
      clinical trials, which are the major instrument for evidence-based medicine, have
      been conducted in this area. Clinical research is essential for the discovery of
      new knowledge, improvement of scientific basis, resolution of challenges, and
      good clinical practice. Some basic principles for a successful researcher include
      interest, availability, persistence, and honesty. It is essential to learn how to
      write a protocol research and to know the international and national regulatory
      rules. A complete clinical trial protocol should include question, background,
      objectives, methodology (design, variable description, sample size,
      randomization, inclusion and exclusion criteria, intervention, efficacy and
      safety measures, and statistical analysis), consent form, clinical research form,
      and references. Institutional ethical review board approval and financial support
      disclosure are necessary. Publication of positive or negative results should be
      an authors' commitment.

PMID- 23539007
TI  - Mechanisms regulating melanogenesis.
AB  - Skin pigmentation is an important human phenotypic trait whose regulation, in
      spite of recent advances, has not yet been fully understood. The pigment melanin
      is produced in melanosomes by melanocytes in a complex process called
      melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and
      central nervous systems, and its activity is also regulated by extrinsic factors
      such as ultraviolet radiation and drugs. We have carried out a review of the
      current understanding of intrinsic and extrinsic factors regulating skin
      pigmentation, the melanogenesis stages and related gene defects. We focused on
      melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor
      (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic
      hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of
      ultraviolet-induced skin pigmentation. The identification and comprehension of
      the melanogenesis mechanism facilitate the understanding of the pathogenesis of
      pigmentation disorders and the development of potential therapeutic options.

PMID- 23539008
TI  - Clear cell acanthoma of the areola and nipple: clinical, histopathological, and
      immunohistochemical features of two Brazilian cases.
AB  - Clear cell acanthoma or Degos' acanthoma is a distinct disease concerning its
      clinical, histopathological, and immunohistochemical features. Its pathologic
      nature - whether neoplastic or reactive - is still under dispute among
      researchers. The disease shows a chronic course and often presents with a single
      papulonodular lesion on the lower limbs of adults. However, cases with multiple
      lesions, sometimes occurring in an eruptive fashion, and with clear variation in
      the size and shape of the cutaneous lesions have been reported. So far, five
      cases in which the lesions were exclusively located in the nipple area have been
      reported, all in Korean women. Four of these cases mimicked eczema and one, a
      polypoid nodule. The aim of this article is to present clinical,
      histopathological, and immunohistochemical features of two additional cases in
      Brazilian women with similar nipple topography.

PMID- 23539009
TI  - Scanning electron microscopy of molluscum contagiosum.
AB  - Molluscum contagiosum is a disease caused by a poxvirus. It is more prevalent in
      children up to 5 years of age. There is a second peak of incidence in young
      adults. In order to examine its ultrastructure, three lesions were curetted
      without disruption, cut transversely with a scalpel, and routinely processed for
      scanning electron microscopy (SEM). The oval structure of molluscum contagiosum
      could be easily identified. In its core, there was a central umbilication and
      just below this depression, there was a keratinized tunnel. Under higher
      magnification, a proliferation similar to the epidermis was seen. Moreover, there
      were areas of cells disposed like a mosaic. Under higher magnification, rounded
      structures measuring 0.4 micron could be observed at the end of the keratinized
      tunnel and on the surface of the lesion.

PMID- 23539010
TI  - Allopurinol in the treatment of acquired reactive perforating collagenosis.
AB  - Acquired reactive perforating collagenosis is a perforating dermatosis usually
      associated with different systemic diseases, mainly diabetes mellitus and/or
      chronic renal insufficiency. Different therapies have been tried but treatment is
      not standardized yet and remains a challenge. In the last few years, allopurinol
      has been reported as a good therapeutic option for acquired reactive perforating
      collagenosis. We describe the case of a 73-year-old man affected by acquired
      reactive perforating collagenosis associated with diabetes type 1 and chronic
      renal failure with secondary hyperparathyroidism. The patient was successfully
      treated with allopurinol 100mg once/day p.o..

PMID- 23539011
TI  - Cutaneous tuberculous gummas in a patient with polymyositis.
AB  - Metastatic tuberculous abscesses or cutaneous tuberculous gummas occur mostly by
      reactivation of ancient cutaneous foci and is triggered mainly by pharmacological
      immunosuppression, diabetes mellitus, alcoholism or acquired immunodeficiency
      syndrome. The present case report refers to a 33-year-old male patient with
      polymyositis and a previous diagnosis of treated pulmonary tuberculosis. He
      presented cutaneous abscesses and fever months after the tuberculosis regimen.
      The patient was diagnosed as metastatic tuberculous abscesses associated with
      immunosuppression as result of polymyositis treatment.

PMID- 23539012
TI  - Disseminated folliculitis by Mycobacterium fortuitum in an immunocompetent woman.
AB  - Mycobacterium fortuitum is a non-tuberculous fast-growing mycobacterium which is
      frequently acquired from environmental sources such as soil and water. Since it
      is an opportunist pathogen, it is associated with trauma, surgery or
      immunodeficiency. The current report describes a case of Mycobacterium fortuitum
      caused disseminated lesions on the skin of an immunocompetent patient.

PMID- 23539013
TI  - Generalized eruptive histiocytoma: a rare disease in an elderly patient.
AB  - Generalized eruptive histiocytoma is considered an extremely rare subtype of non
      Langerhans cells histiocytosis. In the literature, there are few reports of this
      disease that mainly affects adults. In this report, we present a case of
      generalized eruptive histiocytoma in an elderly patient who had presented
      symptoms for over two months. Multiple erythematous papules, asymptomatic and
      symmetrically distributed were observed on the trunk and limbs. Histological
      examination showed a dense mononuclear cell dermal infiltrate. In the
      immunohistochemical analysis, the cells were CD68 positive, but CD1a, S100 and
      CD34 negative. A diagnosis of generalized eruptive histiocytoma was established.
      The aim of our paper is to report a case of a very rare disease, whose subtype
      and affected age group are even more unusual.

PMID- 23539014
TI  - Progressive symmetrical erythrokeratodermia -- case report.
AB  - Progressive symmetrical erythrokeratodermia is a rare autosomal dominant
      genodermatosis with variable penetrance described by Darier in 1911. It is
      characterized by erythematous and keratotic plaques, sharply defined and
      symmetrically distributed along the extremities, buttocks and, more rarely, on
      the face. We report a case of a 55-year-old patient with lesions on the dorsum of
      the hands, interphalangeal pads, wrists, groin and back feet. This case
      demonstrates a rare and late diagnosis, clinical profusion and presence of
      familiar involvement.

PMID- 23539015
TI  - Sarcoid-like lesions in paracoccidioidomycosis: immunological factors.
AB  - The clinical presentation of paracoccidioidomycosis is spectral. Spontaneous
      cure, state of latency or active disease with different levels of severity can
      occur after the hematogenous dissemination. The morphology and number of skin
      lesions will depend on the interaction of host immunity, which is specific and
      individual, and fungus virulence. Some individuals have natural good immunity,
      which added to the low virulence of the fungus maintain the presence of well
      marked granulomas with no microorganism and negative serology for a long time,
      making the diagnosis a challenge. Factors inherent to the fungus, however, may
      modulate the immune response and modify the clinical picture over the time. We
      present a sarcoidosis-like clinical presentation and discuss the immunological
      factors involved.

PMID- 23539016
TI  - Toxic epidermal necrolysis induced by lansoprazole.
AB  - Toxic epidermal necrolysis is a rare, severe cutaneous reaction, mostly caused by
      drugs. It affects the skin and mucous membranes, with involvement of more than
      30% of body surface. We describe the case of a young woman, previously healthy,
      who developed skin detachment of more than 90% of the body surface 15 days after
      being administered lansoprazole for peptic disease. The treatment consisted in
      discontinuation of the drug involved and early administration of intravenous
      human immunoglobulin, which led to a satisfactory outcome of the case,
      substantiating the impact of early diagnosis and treatment on the morbidity and
      mortality of these patients.

PMID- 23539018
TI  - Biopsy guided by dermoscopy in cutaneous pigmented lesion -- case report.
AB  - It may be clinically difficult to differentiate early-stage melanoma from benign
      tumors, specially pigmented seborrheic keratosis. Dermoscopy can help; however,
      the findings are not always conclusive. Therefore, histopathology may be
      necessary for a correct diagnosis. We describe a melanocytic lesion with dubious
      clinic and dermoscopic findings. An incisional biopsy of a suspicious area,
      guided by dermoscopy, was performed to clarify the findings.

PMID- 23539017
TI  - Umbilical endometriosis: report of a case and its dermoscopic features.
AB  - Cutaneous endometriosis is a rare manifestation of endometriosis, representing
      0.5% to 1% of all endometriosis cases. It can be divided into primary and
      secondary, when appearing spontaneously or after a surgical procedure, when it is
      mostly found on surgical scar tissue. Some etiologies were proposed, but none of
      them could entirely explain the appearance of the tumor. Differential diagnosis
      includes melanoma, metastatic nodule, keloid and pyogenic granuloma. Dermoscopic
      features are not yet well established, but there are some characteristics that
      suggest the diagnosis. Treatment is surgical in larger sized lesions.
      Malignization can occur. The screening for endometriosis is mandatory by means of
      gynecologic, imaging and marked-tumor evaluation. We report a case of primary
      umbilical endometriosis and discuss its dermoscopic aspects.

PMID- 23539019
TI  - Dermoscopy revealing a case of Tinea Nigra.
AB  - Dermoscopy has being used over the past twenty years as a noninvasive aid in the
      diagnosis of innumerable skin conditions, including infectious diseases and
      infestations (Entodermoscopy).Tinea nigra is a superficial phaeohyfomycosis that
      affects mainly the glabrous skin of palms and soles. We describe a 14 year-old
      girl with a three-month history of an enlarging brown patch of her hand diagnosed
      as Tinea Nigra following clinical and dermoscopy examination.These images
      emphasize the importance of dermoscopy as a diagnostic tool in the daily routine
      of dermatologists.

PMID- 23539020
TI  - Case for diagnosis.
AB  - Blastic plasmacytoid dendritic cell tumor is a rare, highly aggressive systemic
      neoplasm for which effective therapies have not yet been established. We describe
      a 73-year-old man with multiple nodules and patches emerging on the trunk and
      limbs. Lesional skin biopsy revealed a plasmacytoid dendritic cell tumor with
      dense dermal infiltrate of tumor cells with blastoid features. No apparent
      systemic involvement was identified in the initial stage. The patient was treated
      with prednisone daily, with notorious improvement of the skin lesions, although
      no complete remission was obtained. During the six-month follow-up period, no
      disease progression was documented, but fatal systemic progression occurred after
      that period of time.

PMID- 23539021
TI  - Do you know this syndrome?
AB  - Congenital hypotrichosis and Stargardt macular dystrophy are rare autosomal
      recessive disorder of unknown etiology respectively characterized by hair loss,
      macular degeneration and severe progressive vision reduction. There are few
      reports in the literature with this association. Studies show that the defective
      gene is on the chromosome I6q22.1 and involve cadherin molecule in the
      pathogenesis. Early recognition of these disorders often starts with hair changes
      and should alert the dermatologist for an eye examination thereby avoiding more
      severe ocular defect.

PMID- 23539022
TI  - Combined treatment with botulinum toxin and hyaluronic acid to correct unsightly
      lateral-chin depression.
AB  - With aging, anatomical changes are observed in the face. In the lower third,
      these changes are expressed as ptosis of the angle of the mouth, lip enhancement
      groove mentalis; decrease in concavity between the jaw and neck and very
      noticeable platysmal banding. The repeated contraction of muscles of the lateral
      chin together with the band platysmal side form what are called a marionette
      groove. Treating the whole lateral-chin area can result in a more harmonious
      aspect of the face when compared with treatment of a marionette groove in
      isolation. In this paper we describe combined treatment of the lateral chin area
      using botulinum toxin and fillers.

PMID- 23539023
TI  - The use of nested Polymerase Chain Reaction (nested PCR) for the early diagnosis
      of Histoplasma capsulatum infection in serum and whole blood of HIV-positive
      patients.
AB  - The aim of the study was to detect the rDNA sequences and their regions in
      Histoplasma capsulatum, which could be considered species-specific and used as a
      molecular method for this diagnosis by the technique of nested polymerase chain
      reaction (nested PCR), employing specific sequences (primers) for H. capsulatum:
      18S rDNA region (HC18), 100 kDa (HC100) and the sequence 5.8 S-ITS rDNA (HC5.8).
      The PCR sequences HC18, HC100 and HC5.8 resulted in a specificity of 100%. The
      molecular assays may increase the specificity, sensitivity and speed in the
      diagnosis of Histoplasmosis.

PMID- 23539025
TI  - Development of an optical gas leak sensor for detecting ethylene, dimethyl ether
      and methane.
AB  - In this paper, we present an approach to develop an optical gas leak sensor that
      can be used to measure ethylene, dimethyl ether, and methane. The sensor is
      designed based on the principles of IR absorption spectrum detection, and
      comprises two crossed elliptical surfaces with a folded reflection-type optical
      path. We first analyze the optical path and the use of this structure to design a
      miniature gas sensor. The proposed sensor includes two detectors (one to acquire
      the reference signal and the other for the response signal), the light source,
      and the filter, all of which are integrated in a miniature gold-plated chamber.
      We also designed a signal detection device to extract the sensor signal and a
      microprocessor to calculate and control the entire process. The produced sensor
      prototype had an accuracy of +/-0.05%. Experiments which simulate the
      transportation of hazardous chemicals demonstrated that the developed sensor
      exhibited a good dynamic response and adequately met technical requirements.

PMID- 23539027
TI  - Photonic crystal structures with tunable structure color as colorimetric sensors.
AB  - Colorimetric sensing, which transduces environmental changes into visible color
      changes, provides a simple yet powerful detection mechanism that is well-suited
      to the development of low-cost and low-power sensors. A new approach in
      colorimetric sensing exploits the structural color of photonic crystals (PCs) to
      create environmentally-influenced color-changeable materials. PCs are composed of
      periodic dielectrics or metallo-dielectric nanostructures that affect the
      propagation of electromagnetic waves (EM) by defining the allowed and forbidden
      photonic bands. Simultaneously, an amazing variety of naturally occurring
      biological systems exhibit iridescent color due to the presence of PC structures
      throughout multi-dimensional space. In particular, some kinds of the structural
      colors in living organisms can be reversibly changed in reaction to external
      stimuli. Based on the lessons learned from natural photonic structures, some
      specific examples of PCs-based colorimetric sensors are presented in detail to
      demonstrate their unprecedented potential in practical applications, such as the
      detections of temperature, pH, ionic species, solvents, vapor, humidity, pressure
      and biomolecules. The combination of the nanofabrication technique, useful design
      methodologies inspired by biological systems and colorimetric sensing will lead
      to substantial developments in low-cost, miniaturized and widely deployable
      optical sensors.

PMID- 23539028
TI  - Rapid and highly sensitive detection of lead ions in drinking water based on a
      strip immunosensor.
AB  - In this study, we have first developed a rapid and sensitive strip immunosensor
      based on two heterogeneously-sized gold nanoparticles (Au NPs) probes for the
      detection of trace lead ions in drinking water. The sensitivity was 4-fold higher
      than that of the conventional LFA under the optimized conditions. The visual
      limit of detection (LOD) of the amplified method for qualitative detection lead
      ions was 2 ng/mL and the LOD for semi-quantitative detection could go down to
      0.19 ng/mL using a scanning reader. The method suffered from no interference from
      other metal ions and could be used to detect trace lead ions in drinking water
      without sample enrichment. The recovery of the test samples ranged from 96% to
      103%. As the detection method could be accomplished within 15 min, this method
      could be used as a potential tool for preliminary monitoring of lead
      contamination in drinking water.

PMID- 23539029
TI  - Optical flow and driver's kinematics analysis for state of alert sensing.
AB  - Road accident statistics from different countries show that a significant number
      of accidents occur due to driver's fatigue and lack of awareness to traffic
      conditions. In particular, about 60% of the accidents in which long haul truck
      and bus drivers are involved are attributed to drowsiness and fatigue. It is thus
      fundamental to improve non-invasive systems for sensing a driver's state of
      alert. One of the main challenges to correctly resolve the state of alert is
      measuring the percentage of eyelid closure over time (PERCLOS), despite the
      driver's head and body movements. In this paper, we propose a technique that
      involves optical flow and driver's kinematics analysis to improve the robustness
      of the driver's alert state measurement under pose changes using a single camera
      with near-infrared illumination. The proposed approach infers and keeps track of
      the driver's pose in 3D space in order to ensure that eyes can be located
      correctly, even after periods of partial occlusion, for example, when the driver
      stares away from the camera. Our experiments show the effectiveness of the
      approach with a correct eyes detection rate of 99.41%, on average. The results
      obtained with the proposed approach in an experiment involving fifteen persons
      under different levels of sleep deprivation also confirm the discriminability of
      the fatigue levels. In addition to the measurement of fatigue and drowsiness, the
      pose tracking capability of the proposed approach has potential applications in
      distraction assessment and alerting of machine operators.

PMID- 23539026
TI  - Quantitative phase imaging techniques for the study of cell pathophysiology: from
      principles to applications.
AB  - A cellular-level study of the pathophysiology is crucial for understanding the
      mechanisms behind human diseases. Recent advances in quantitative phase imaging
      (QPI) techniques show promises for the cellular-level understanding of the
      pathophysiology of diseases. To provide important insight on how the QPI
      techniques potentially improve the study of cell pathophysiology, here we present
      the principles of QPI and highlight some of the recent applications of QPI
      ranging from cell homeostasis to infectious diseases and cancer.

PMID- 23539030
TI  - Fourier transform infrared spectroscopy (FTIR) and multivariate analysis for
      identification of different vegetable oils used in biodiesel production.
AB  - The main objective of this study was to use infrared spectroscopy to identify
      vegetable oils used as raw material for biodiesel production and apply
      multivariate analysis to the data. Six different vegetable oil sources--canola,
      cotton, corn, palm, sunflower and soybeans--were used to produce biodiesel
      batches. The spectra were acquired by Fourier transform infrared spectroscopy
      using a universal attenuated total reflectance sensor (FTIR-UATR). For the
      multivariate analysis principal component analysis (PCA), hierarchical cluster
      analysis (HCA), interval principal component analysis (iPCA) and soft independent
      modeling of class analogy (SIMCA) were used. The results indicate that is
      possible to develop a methodology to identify vegetable oils used as raw material
      in the production of biodiesel by FTIR-UATR applying multivariate analysis. It
      was also observed that the iPCA found the best spectral range for separation of
      biodiesel batches using FTIR-UATR data, and with this result, the SIMCA method
      classified 100% of the soybean biodiesel samples.

PMID- 23539031
TI  - 2-D unitary ESPRIT-like direction-of-arrival (DOA) estimation for coherent
      signals with a uniform rectangular array.
AB  - A unitary transformation-based algorithm is proposed for two-dimensional (2-D)
      direction-of-arrival (DOA) estimation of coherent signals. The problem is solved
      by reorganizing the covariance matrix into a block Hankel one for decorrelation
      first and then reconstructing a new matrix to facilitate the unitary
      transformation. By multiplying unitary matrices, eigenvalue decomposition and
      singular value decomposition are both transformed into real-valued, so that the
      computational complexity can be reduced significantly. In addition, a fast and
      computationally attractive realization of the 2-D unitary transformation is given
      by making a Kronecker product of the 1-D matrices. Compared with the existing 2-D
      algorithms, our scheme is more efficient in computation and less restrictive on
      the array geometry. The processing of the received data matrix before unitary
      transformation combines the estimation of signal parameters via rotational
      invariance techniques (ESPRIT)-Like method and the forward-backward averaging,
      which can decorrelate the impinging signalsmore thoroughly. Simulation results
      and computational order analysis are presented to verify the validity and
      effectiveness of the proposed algorithm.

PMID- 23539032
TI  - An optofluidic temperature probe.
AB  - We report the application of a microfluidic device for semi-contact temperature
      measurement in picoliter volumes of aqueous media. Our device, a freely
      positionable multifunctional pipette, operates by a hydrodynamic confinement
      principle, i.e., by creating a virtual flow cell of micrometer dimensions within
      a greater aqueous volume. We utilized two fluorescent rhodamines, which exhibit
      different fluorescent responses with temperature, and made ratiometric intensity
      measurements. The temperature dependence of the intensity ratio was calibrated
      and used in a model study of the thermal activation of TRPV1 ion channels
      expressed in Chinese hamster ovary cells. Our approach represents a practical and
      robust solution to the specific problem of measuring temperature in biological
      experiments in vitro, involving highly localized heat generation, for example
      with an IR-B laser.

PMID- 23539033
TI  - Use of high sensitivity GNSS receiver Doppler measurements for indoor pedestrian
      dead reckoning.
AB  - Dead-reckoning (DR) algorithms, which use self-contained inertial sensors
      combined with gait analysis, have proven to be effective for pedestrian
      navigation purposes. In such DR systems, the primary error is often due to
      accumulated heading drifts. By tightly integrating global navigation satellite
      system (GNSS) Doppler measurements with DR, such accumulated heading errors can
      usually be accurately compensated. Under weak signal conditions, high sensitivity
      GNSS (HSGNSS) receivers with block processing techniques are often used, however,
      the Doppler quality of such receivers is relatively poor due to multipath, fading
      and signal attenuation. This often limits the benefits of integrating HSGNSS
      Doppler with DR. This paper investigates the benefits of using Doppler
      measurements from a novel direct vector HSGNSS receiver with pedestrian dead
      reckoning (PDR) for indoor navigation. An indoor signal and multipath model is
      introduced which explains how conventional HSGNSS Doppler measurements are
      affected by indoor multipath. Velocity and Doppler estimated by using direct
      vector receivers are introduced and discussed. Real experimental data is
      processed and analyzed to assess the veracity of proposed method. It is shown
      when integrating HSGNSS Doppler with PDR algorithm, the proposed direct vector
      method are more helpful than conventional block processing method for the indoor
      environments considered herein.

PMID- 23539034
TI  - Nonlinear detection for a high rate extended binary phase shift keying system.
AB  - The algorithm and the results of a nonlinear detector using a machine learning
      technique called support vector machine (SVM) on an efficient modulation system
      with high data rate and low energy consumption is presented in this paper.
      Simulation results showed that the performance achieved by the SVM detector is
      comparable to that of a conventional threshold decision (TD) detector. The two
      detectors detect the received signals together with the special impacting filter
      (SIF) that can improve the energy utilization efficiency. However, unlike the TD
      detector, the SVM detector concentrates not only on reducing the BER of the
      detector, but also on providing accurate posterior probability estimates (PPEs),
      which can be used as soft-inputs of the LDPC decoder. The complexity of this
      detector is considered in this paper by using four features and simplifying the
      decision function. In addition, a bandwidth efficient transmission is analyzed
      with both SVM and TD detector. The SVM detector is more robust to sampling rate
      than TD detector. We find that the SVM is suitable for extended binary phase
      shift keying (EBPSK) signal detection and can provide accurate posterior
      probability for LDPC decoding.

PMID- 23539035
TI  - Violent behavior and hallucination in a 32-year-old patient.

PMID- 23539036
TI  - Commentary.

PMID- 23539037
TI  - Commentary.

PMID- 23539038
TI  - Metabolic acidosis with discrepant lactate results.

PMID- 23539041
TI  - Epidemics and fear.

PMID- 23539042
TI  - Activities of acyl-CoA:diacylglycerol acyltransferase (DGAT) and
      phospholipid:diacylglycerol acyltransferase (PDAT) in microsomal preparations of
      developing sunflower and safflower seeds.
AB  - The last step in triacylglycerols (TAG) biosynthesis in oil seeds, the acylation
      of diacylglycerols (DAG), is catalysed by two types of enzymes: the acyl
      CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol
      acyltransferase (PDAT). The relative contribution of these enzymes in the
      synthesis of TAG has not yet been defined in any plant tissue. In the presented
      work, microsomal preparations were obtained from sunflower and safflower seeds at
      different stages of development and used in DGAT and PDAT enzyme assays. The
      ratio between PDAT and DGAT activity differed dramatically between the two
      different species. DGAT activities were measured with two different acyl
      acceptors and assay methods using two different acyl-CoAs, and in all cases the
      ratio of PDAT to DGAT activity was significantly higher in safflower than
      sunflower. The sunflower DGAT, measured by both methods, showed significant
      higher activity with 18:2-CoA than with 18:1-CoA, whereas the opposite
      specificity was seen with the safflower enzyme. The specificities of PDAT on the
      other hand, were similar in both species with 18:2-phosphatidylcholine being a
      better acyl donor than 18:1-PC and with acyl groups at the sn-2 position utilised
      about fourfold the rate of the sn-1 position. No DAG:DAG transacylase activity
      could be detected in the microsomal preparations.

PMID- 23539043
TI  - Complications of medial patellofemoral ligament reconstruction in young patients.
AB  - BACKGROUND: The medial patellofemoral ligament (MPFL) has been recognized as the
      primary restraint to lateral subluxation of the patella. Reconstruction of the
      MPFL for patellar instability has demonstrated early clinical success, but
      postoperative complications have rarely been reported, especially in young
      patients. PURPOSE: To assess early complications (<3 years) of MPFL
      reconstruction in young patients. STUDY DESIGN: Case series; Level of evidence,
      4. METHODS: The charts and radiographs of all patients who underwent MPFL
      reconstruction between 2005 and 2011 were retrospectively reviewed to identify
      postoperative complications. A complication was considered major if the patient
      required hospitalization or further surgery. Each complication was analyzed to
      identify the technical factors related to it. RESULTS: A total of 179 knees
      underwent MPFL reconstruction during the study period. There were 38
      complications in 29 knees (16.2%), with 34 major and 4 minor. Major complications
      included recurrent lateral patellar instability (8 patients), knee motion
      stiffness with flexion deficits (8 patients), patellar fractures (6 patients),
      and patellofemoral arthrosis/pain (5 patients). Eighteen of 38 (47%)
      complications were secondary to technical factors and were considered
      preventable. Female sex and bilateral MPFL reconstructions were risk factors
      associated with postoperative complications. CONCLUSION: Complications occurred
      in 16.2% of MPFL reconstruction surgeries for patellar instability in young
      patients, with almost half resulting from technical problems. Patients should be
      counseled preoperatively on the risk of potential complications.

PMID- 23539045
TI  - Recent advances in the molecular and genetic understanding of congenital
      gastrointestinal malformations.
AB  - Major developmental paradigms are highly conserved among vertebrates. The
      contribution of developmental biology to the understanding of human disease and
      regeneration has soared recently. We review advances in the molecular and genetic
      understanding of gastrointestinal development using evidence from both mammalian
      and nonmammalian models. When appropriate, we highlight relevance and
      applicability to human disease.

PMID- 23539044
TI  - Mesenchymal stem cells from a hypoxic culture improve and engraft Achilles tendon
      repair.
AB  - BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) from humans
      cultured under hypoxic conditions increase bone healing capacity. HYPOTHESIS: Rat
      MSCs cultured under hypoxic conditions increase the tendon healing potential
      after transplantation into injured Achilles tendons. STUDY DESIGN: Controlled
      laboratory study. METHODS: Biomechanical testing, histological analysis, and
      bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to
      demonstrate that augmentation of an Achilles tendon rupture site with hypoxic
      MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty
      Sprague-Dawley rats were used for the experiments, with 2 rats as the source of
      bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into
      3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut
      tendons served as normal uncut controls. Outcome measures included mechanical
      testing in 24 rats, histological analysis, and BrdU labeling/collagen
      immunohistochemistry in another 24 rats. RESULTS: The ultimate failure load in
      the hypoxic MSC group was significantly greater than that in the nontreated or
      normoxic MSC group at 2 weeks after incision (2.1 N/mm(2) vs 1.1 N/mm(2) or 1.9
      N/mm(2), respectively) and at 4 weeks after incision (5.5 N/mm(2) vs 1.7 N/mm(2)
      or 2.7 N/mm(2), respectively). The ultimate failure load in the hypoxic MSC group
      at 4 weeks after incision (5.5 N/mm(2)) was close to but still significantly less
      than that of the uncut tendon (7.2 N/mm(2)). Histological analysis as determined
      by the semiquantitative Bonar histopathological grading scale revealed that the
      hypoxic MSC group underwent a significant improvement in Achilles tendon healing
      both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via
      statistical analysis. Immunohistochemistry further demonstrated that the hypoxic
      and normoxic MSC groups had stronger immunostaining for type I and type III
      collagen than did the nontreated group both at 2 and 4 weeks after incision.
      Moreover, BrdU labeling of MSCs before injection further determined the
      incorporation and retention of transplanted cells at the rupture site.
      CONCLUSION: Transplantation of hypoxic MSCs may be a better and more readily
      available treatment than normoxic MSCs for Achilles tendon ruptures. CLINICAL
      RELEVANCE: The present study provides evidence that transplantation of hypoxic
      MSCs may be a promising therapy for the treatment of Achilles tendon ruptures.

PMID- 23539046
TI  - Sirolimus as rescue therapy in pediatric autoimmune hepatitis.

PMID- 23539047
TI  - Incidence and prevalence of eosinophilic esophagitis in children.
AB  - OBJECTIVES: The aim of the present study was to conduct a systematic review with
      meta-analysis on the epidemiology of eosinophilic esophagitis (EoE) in children.
      METHODS: Studies investigating incidence and prevalence of EoE in children (<= 18
      years) were identified in a systematic review of MEDLINE (1950-2011) and Embase
      (1980-2011). Meta-analyses were performed for incidence and subgroups with >= 5
      studies: esophagogastroduodenoscopy (EGD) for any indication, histologic
      esophageal disease, and celiac disease, and EGD for abdominal pain. We used a
      random effects model, Q statistic to assess heterogeneity, and joinpoint analysis
      to assess time trends. RESULTS: We included 25 studies. The incidence of EoE
      varied from 0.7 to 10/100,000 per person-year and the prevalence ranged from 0.2
      to 43/100,000. The incidence and prevalence increased over time. Prevalence was
      highest in children with food impaction or dysphagia (63%-88%). The pooled
      prevalence was 3.7% (95% confidence interval [CI] 2.4-5.1) in EGD for any
      indication, 24% (95% CI 19-28) in histologic esophageal disease, 2.3% (95% CI 1.0
      3.6) in celiac disease, and 2.6% (95% CI 1.2-4.1) in EGD for abdominal pain.
      CONCLUSIONS: During the last 2 decades, the incidence and prevalence of EoE in
      children have increased significantly; however, the population-based incidence
      and prevalence of EoE vary widely across geographic variations, potentially
      because of variations in case of ascertainment between centers. Because EoE is
      common among children with food impaction and dysphagia, children with this
      presenting complaint should be rapidly identified at triage for timely endoscopic
      assessment.

PMID- 23539048
TI  - Application and limitations of transient liver elastography in children.
AB  - OBJECTIVES: Transient elastography (TE) using the FibroScan has gained popularity
      recently for the noninvasive diagnosis of hepatic fibrosis. Data on its use in
      children younger than 6 years are still scarce, and the influence of technical
      aspects such as probe choice and site of measurement on FibroScan results is not
      clear. Our study aims to clarify some technical issues concerning the use of the
      FibroScan in children and to deliver normal FibroScan values for reference.
      METHODS: TE was performed in 527 children (229 girls, ages 0.1-17.8 [median 6.0]
      years, including 400 healthy controls). Feasibility of different sites of
      measurements, paired comparison of probe settings, and pre- and postprandial
      measurements were systematically performed. Sedated versus unsedated measurements
      were compared in age- and sex-matched cohorts. RESULTS: Success rate of TE in our
      population was 90%, but decreased to 83% in children younger than 24 months even
      in ideal conditions. General anesthesia significantly increased liver stiffness
      in healthy children (5.4 [3-9.5] vs 4.2 [2.8-8.15] kPa; P < 0.01). Probe choice
      equally influenced results in paired comparisons (S1 5.5 [3.5-17.9] vs S2 4.8
      [2.1-15.4] kPa; P < 0.01), as did food intake (5.9 [3.6-75] vs 5.4 [3.6-63.9]
      kPa; P = 0.015). Inter- and intraobserver agreements were good. Normal liver
      stiffness was 4.5 (2.5-8.9) kPa and did not vary significantly with age or sex.
      CONCLUSIONS: TE is feasible even in extremely young children, but confounding
      influences on test results such as probe choice, sedation, or food intake need to
      be taken into account when interpreting results.

PMID- 23539049
TI  - Transient benign hyperphophatasemia.
AB  - BACKGROUND AND AIM: Sometimes, a temporary increase in alkaline phosphatase level
      is found in healthy infants and toddlers without evidence of liver or bone
      disease. The condition is customarily termed transient benign hyperphosphatasemia
      of infancy and early childhood. Most textbooks do not refer to the condition. The
      aim of the study was to promote broader awareness of transient benign
      hyperphosphatasemia. METHODS: We completed a systematic review of the literature
      using the principles underlying the UK Economic and Social Research Council
      guidance on the conduct of narrative synthesis and the Preferred Reporting Items
      for Systematic Reviews and Meta-analyses statement. RESULTS: The 142 reports
      retained for analysis included 813 cases (male:female ratio 1.1:1.0): 80 in
      subjects older than 18 years and 733 in subjects 18 years or younger. The
      alkaline phosphatase ratio, calculated by dividing the measured level by the
      upper limit of normal, was >=5.0 in ~70% and the duration of the elevation was
      <=4 months in 80% of the cases. Transient benign hyperphosphatasemia often
      followed a benign infection, but available data fail to demonstrate a causal
      link. The prevalence of transient benign hyperphosphatasemia ranged from 1.1% to
      3.5% in infants 2 to 24 months of age. CONCLUSIONS: Transient benign
      hyperphosphatasemia is likely the most common cause of hyperphosphatasemia among
      healthy infants and toddlers. Sometimes it also occurs in older children and
      adults, indicating that the traditional term transient benign hyperphosphatasemia
      of infancy and early childhood may not be correct. The elevation in alkaline
      phosphatase persists for >4 months in ~20% of the cases. Recognition of this
      benign condition is crucial to avoid unnecessary investigations.

PMID- 23539050
TI  - Is a legacy effect possible in IgA nephropathy?
AB  - The term 'legacy effect'--a memory of a treatment which produces benefits long
      after the cessation of the intervention--was adopted for the first time to
      describe the benefits of early and strict control of diabetes on cardiovascular
      complications. The search for a similar effect for early treatment of immune
      mediated renal diseases, interrupting some self-amplification loops of the
      pathogenetical immunological mechanisms and leaving a permanent memory, is
      fascinating. Some recent reports suggest a long-term beneficial or legacy effect
      of early treatment of IgA nephropathy after a randomized controlled trial (RCT)
      using mycophenolate mofetil, methylprednisolone pulses or
      steroid/immunosuppressive multiple therapy, or prolonged steroid doses associated
      with tonsillectomy. Long-lasting effects of treatments are more likely to be
      achieved in early stages of IgA nephropathy, when mesangial proliferative or
      endocapillary hypercellular lesions are pre-eminent over sclerosis, and when
      proteinuria is not massive, above all in young patients. The long-term results
      considered are relevant, but have the counterpart of the risk of drug toxicity or
      side effects, which are particularly undesired in patients with a mild disease.
      Hence, there is interest for drugs targeting the intestinal mucosal immunity with
      a little systemic effect, aimed at interrupting the initial pathogenetical
      mechanism. The possibility of modulating anti-inflammatory regulatory T cells by
      modifying inducible enzymes is another fascinating field of future research.

PMID- 23539051
TI  - [Revista de Gastroenterologia del Peru: a new era].

PMID- 23539052
TI  - [Validation of a modified version of SODA questionnaire (severity of dyspepsia
      assessment) adapted to Peru for evaluating evolution of symptoms severity in
      patients with dyspepsia].
AB  - OBJECTIVES: To validate SODA (severity of dyspepsia assessment) questionnaire in
      our population for evaluating symptoms severity in patients with dyspepsia.
      MATERIALS AND METHODS: Content and appearance validity were measured, and then a
      modified questionnaire was developed. A pilot test was made and reliability,
      construct validity and responsiveness were measured. RESULTS: An adequate content
      and appearance validity were obtained. On the pilot test, reliability of the
      complete questionnaire and by components had Cronbach alpha values over 0,7.
      Construct validity of SODA was evaluated by correlating modified SODA results
      with SF-36 scores using Pearson test: -0.72 (p<0.001). When we compared results
      of modified SODA questionnaire and the score of a question about subjective
      perception of the disease using Spearman test we obtained similar results: 0.72
      (p<0.001). Two means of SODA questionnaire scores, before and after treatment,
      were compared using Student's T test, and a significant difference was found,
      (p<0.001) with a drop mean of 5.70 +/-5.33. CONCLUSION: Modified SODA
      questionnaire meets all criteria of validity and it could be used to measure
      dyspepsia severity and its evolution in a Peruvian population.

PMID- 23539053
TI  - [Dyspepsia: clinical characteristics, endoscopic and histological findings in
      patients of the Hospital Nacional Hipolito Unanue, Lima, Peru, during 2010].
AB  - OBJECTIVE: To identify clinical, endoscopic and histological characteristics and
      their relationship with Helicobacter pylori (Hp) in patients treated with the
      diagnosis of dyspepsia in our hospital during 2010. MATERIALS AND METHODS: We
      conducted a cross sectional and retrospective study in the population attending
      our hospital during 2010, a sample of 300 patients was studied. We evaluated
      clinical, histological and endoscopic findings. An instrument of data collection
      was made. We used the statistical package SPSS 15.0. RESULTS: It was found that
      the majority were female (63%), while the mean age at diagnosis was 42 years,
      mostly from SJL district (30%) of these Andean origin (50 %) was the highest
      percentage. Only 19% showed signs of alarm, low weight characterize this group
      (14%), the endoscopic findings most commonly found were antral erythema (74.7%),
      followed by erosions (32.9%) and nodules (22%). Hp infection was found in 93%,
      mild dysplasia was present in 2.7% and atrophy in only 14.7%. The 98.5% of
      patients with nodularity on endoscopy had Hp infection. CONCLUSIONS: The most
      frequent dyspeptic symptoms were epigastric pain followed by abdominal
      distension, the female gender was present more often, the warning signs were
      rare, antral erythema was the feature most found in endoscopies. Hp infection was
      significantly associated with some features such as endoscopic antral nodularity
      and erythema as well as had relation to the activity of gastritis.

PMID- 23539054
TI  - [Adjuvant chemo radiotherapy after gastrectomy and D2 lymphadenectomy in patients
      with gastric cancer in the National Institute of Cancer, Lima, Peru].
AB  - INTRODUCTION: Adjuvant chemo radiotherapy is the standard treatment in Western
      countries in gastric cancer patients submitted to curative resection. INT0116
      pivotal trial established adjuvant chemo radiation as the standard care for
      resected high risk adenocarcinoma of the stomach in US however was hampered by
      suboptimal surgery. There is controversial data about efficacy of this adjuvant
      therapy in patients who have undergone D2 lymphadenectomy predominantly. In our
      hospital D2 lymphadenectomy is standard surgery for gastric cancer. OBJECTIVE: To
      prove that chemo and radio therapy post gastrectomy and D2 linphadenectomy in
      patients' with gastric cancer is effective. MATERIAL AND METHODS: Retrospective
      study with gastric adenocarcinoma patients stage II to IV M0 who underwent
      curative resection at INEN (Instituto Nacional de Enfermedades Neoplasicas) Lima
      Peru between 2001 and 2006. Standard treatment at institution is D2
      lymphadenectomy. Chemo radiotherapy according to INT0116 was given like adjuvant
      therapy. Survivalcurves were calculated according to Kaplan-Meier method and
      compared with log-rank test. RESULTS: 84 patients were included 60.7% male and
      39.3% female. Mean age was 49.5 years old. The pathologic stages were T1-T2
      (15.5%), T3- T4 (84.5%), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was
      performed in all patients. The 3-year DFS was 17% and 3-year overall survival was
      23.9%. However when we analyzed by subgroups the overall survival, was in group
      N1 (66.7%) and in group N2 (58.9%) and N3 (18.3%) and 3 years DFS by subgroups
      were N1 (100%), N2 (51.9%) and N3 (16.3%). CONCLUSIONS: Adjuvant chemo
      radiotherapy decreased risk of death and relapse to three years mainly in
      patients with node positive N1-N2, who underwent curative resection with D2
      lymphadenectomy, but recurrence was most frequent in N3 node positive, maybe is
      necessary improve the chemotherapy in this group of patients for decrease the
      rate of relapse.

PMID- 23539055
TI  - [Eosinophilic and lymphocytic colitis: different histological manifestations of a
      same process in patients with chronic diarrhea].
AB  - OBJECTIVES: 1) To determine the prevalence of increased number of eosinophils in
      colonic mucosa of patients with lymphocytic colitis (LC). 2) To determine the
      coexistence of eosinophilic colitis (EC) in patients with lymphocytic colitis.
      MATERIALS AND METHODS: slides of adult patients with cronic diarrhea with
      diagnosis of LC were reviewed between October 2009 and March 2012. The number of
      eosinophils was quantified. RESULTS: Sixty eight patients with LC were included.
      Elevated eosinophils were found in 76.5 and in 51.4% a diagnosis of EC was
      established. CONCLUSION: 3 out of 4 patients with LC had elevated eosinophils and
      1 of 2 patients with LC had criteria for EC.

PMID- 23539056
TI  - [Stents in the digestive tract: state of the art].
AB  - Stents are devices currently used for palliative and definitive treatment in
      cases of malignant obstructions of the digestive tract and nowadays can be used
      in benign cases like stenosis, fistulas or perforations. The progress made in the
      design and delivery systems of these prostheses have been of extraordinary
      benefit, which consequently are now considered as a minimally invasive treatment.
      The evolution of these prostheses allows patients not only a palliative treatment
      but also a possibility of curative option, due to antimitotic drug release
      (Idionine 125). In addition, the use of biodegradable materials in them, enable
      the reduction of the rate of complication, related with the number of procedures.

PMID- 23539057
TI  - Improving early detection of gastric cancer: a novel systematic alphanumeric
      coded endoscopic approach.
AB  - Despite extensive worldwide use of standard esophagogastroduodenoscopy (EGD)
      examinations, gastric cancer (GC) is one of the most common forms of cancer and
      ranks as the most common malignant tumor in East Asia, Eastern Europe and parts
      of Latin America. Current limitations of using non systematic examination during
      standard EGD could be at least partially responsible for the low incidence of
      early GC diagnosis in countries with a high prevalence of the disease. Originally
      proposed by Emura et al., systematic alphanumeric-coded endoscopy (SACE) is a
      novel method that facilitates complete examination of the upper GI tract based on
      sequential systematic overlapping photo-documentation using an endoluminal
      alphanumeric-coded nomenclature comprised of eight regions and 28 areas covering
      the entire surface upper GI surface. For precise localization or normal or
      abnormal areas, SACE incorporates a simple coordinate system based on the
      identification of certain natural axes, walls, curvatures and anatomical
      endoluminal landmarks. Efectiveness of SACE was recently demonstrated in a
      screening study that diagnosed early GC at a frequency of 0.30% (2/650) in
      healthy, average-risk volunteer subjects. Such a novel approach, if uniformly
      implemented worldwide, could significantly change the way we practice upper
      endoscopy in our lifetimes.

PMID- 23539058
TI  - Adult education. Gastroenterology training today.
AB  - Gastroenterology education has changed in recent years and the quality criteria
      are now the aim of it. Adult education is not intuited, it is to be learned. In
      our days post graduated education needs longer periods of training, because of
      the everyday development of new techniques and also because the e-learning /e
      teaching has appeared in the arena.

PMID- 23539059
TI  - [Intraductal papillary mucinous neoplasm and recurrent pancreatitis].
AB  - Ohashi described for the first time the IPMN on 1982 as a pancreatic neoplasia
      with mucine cells forming papillae and producing dilatation of the main
      pancreatic duct or its branches. The IPMN represent the 1% of the pancreatic
      tumors and 5% of the cystic neoplasias. It is potentially malignant in a period
      of five years being more frequent in males between 60-70 and clinically these
      patients' presents as acute, recurrent or chronic pancreatitis, with an incidence
      of malignancy from 25% to 70%. CT scan and cholangio MRI allows the diagnosis,
      the variety, localization and possibility of determine malignancy. The treatment
      is the Whipple resection. We are reporting the case of an obese middle age male,
      being observed along the last 10 years because of recurrent pancreatitis with a
      cystic lesion of the head of the pancreas. The CT scan, endoscopic-ultrasound and
      the analysis of the liquid content suggested a mucinous lesion, reason why the
      patient underwent a pancreatic-duodenal resection. The histology study confirms
      the diagnosis of IPMN.

PMID- 23539060
TI  - [Endoscopic removal by ERCP of Fasciola hepatica alive: two case reports and
      review of the literature].
AB  - We report two cases of biliary fascioliasis in patients from the highlands of
      Peru; with several months of symptoms characterized for biliary-type pain, dark
      urine and jaundice in one case. Both of them referred to the department of
      Gastroenterology of the Hospital Nacional Guillermo Almenara Irigoyen for
      suspicious of choledocolithiasis. Laboratory tests were performed which showed
      variable high levels of functional liver tests (cholestasis) and marked
      eosinophilia in one case. Magnetic resonance cholangiography (CRMN) was performed
      and then informed as an apparent image of biliary stone in choledocus in both
      cases. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and
      after sphincterotomy, one flattened, lanceolate parasite, with active mobility
      morphologically compatible with Fasciola hepatica was extracted. After the ERCP
      antiparasitic treatment was given with triclabendazole. Clinical outcome was
      favourable.

PMID- 23539061
TI  - [Chronic diarrhea post cholecystectomy].
AB  - In the present article presents the high frequency of previous cholecystectomy as
      determinant factor of chronic diarrhea and its control with cholestyramine.

PMID- 23539062
TI  - Relationship of periodontal clinical parameters with bacterial composition in
      human dental plaque.
AB  - More than 600 bacterial species have been identified in the oral cavity, but only
      a limited number of species show a strong association with periodontitis. The
      purpose of the present study was to provide a comprehensive outline of the
      microbiota in dental plaque related to periodontal status. Dental plaque from 90
      subjects was sampled, and the subjects were clustered based on bacterial
      composition using the terminal restriction fragment length polymorphism of 16S
      rRNA genes. Here, we evaluated (1) periodontal clinical parameters between
      clusters; (2) the correlation of subgingival bacterial composition with
      supragingival bacterial composition; and (3) the association between bacterial
      interspecies in dental plaque using a graphical Gaussian model. Cluster 1 (C1)
      having high prevalence of pathogenic bacteria in subgingival plaque showed
      increasing values of the parameters. The values of the parameters in Cluster 2a
      (C2a) having high prevalence of non-pathogenic bacteria were markedly lower than
      those in C1. A cluster having low prevalence of non-pathogenic bacteria in
      supragingival plaque showed increasing values of the parameters. The bacterial
      patterns between subgingival plaque and supragingival plaque were significantly
      correlated. Chief pathogens, such as Porphyromonas gingivalis, formed a network
      with other pathogenic species in C1, whereas a network of non-pathogenic species,
      such as Rothia sp. and Lautropia sp., tended to compete with a network of
      pathogenic species in C2a. Periodontal status relates to non-pathogenic species
      as well as to pathogenic species, suggesting that the bacterial interspecies
      connection affects dental plaque virulence.

PMID- 23539063
TI  - Diversity of the major capsid genes (g23) of T4-like bacteriophages in the
      eutrophic Lake Kotokel in East Siberia, Russia.
AB  - Numerous studies revealed high diversity of T4-like bacteriophages in various
      environments, but so far, little is known about T4-like virus diversity in
      freshwater bodies, particularly in eutrophic lakes. The present study was aimed
      at elucidating molecular diversity of T4-like bacteriophages in eutrophic Lake
      Kotokel located near Lake Baikal by partial sequencing of the major capsid genes
      (g23) of T4-like bacteriophages. The majority of g23 fragments from Lake Kotokel
      were most similar to those from freshwater lakes and paddy fields. Despite the
      proximity and direct water connection between Lake Kotokel and Lake Baikal, g23
      sequence assemblages from two lakes were different. UniFrac analysis showed that
      uncultured T4-like viruses from Lake Kotokel tended to cluster with those from
      the distant lake of the same trophic status. This fact suggested that the trophic
      conditions affected the formation of viral populations, particularly of T4-like
      viruses, in freshwater environments.

PMID- 23539064
TI  - Antiestrogen Resistance and the Application of Systems Biology.
AB  - Understanding the molecular changes that drive an acquired antiestrogen
      resistance phenotype is of major clinical relevance. Previous methodologies for
      addressing this question have taken a single gene/pathway approach and the
      resulting gains have been limited in terms of their clinical impact. Recent
      systems biology approaches allow for the integration of data from high throughput
      "-omics" technologies. We highlight recent advances in the field of antiestrogen
      resistance with a focus on transcriptomics, proteomics and methylomics.

PMID- 23539065
TI  - An observational and descriptive study of the epidemiology of and therapeutic
      approach to onychomycosis in dermatology offices in Brazil.
AB  - BACKGROUND: Onychomycosis is a type of fungal infection that accounts for over
      50% of all onycopathies. Some authors consider superficial mycosis the most
      difficult to be treated. Very few studies have been carried out in order to
      assess the epidemiology of onychomycosis in Brazil. OBJECTIVE: To describe the
      epidemiological profile of onychomycosis in Brazilian dermatology offices and to
      assess the etiology of the disease, how often mycosis exams are requested, and
      the treatment adopted. METHODS: A descriptive, observational study was carried
      out between May and July, 2010. Thirty-eight dermatologists from different
      Brazilian regions participated in the study, and 7,852 patients with any skin
      diseases who had all of their nails examined were included in the study. RESULTS:
      Of the 7,852 patients, 28.3% were clinically diagnosed as having onychomycosis.
      Women over 45 years old who practiced exercises or with a personal history of the
      disease showed greater likelihood of having onychomycosis. The disease was most
      seen in the feet, and the majority of cases involved the hallux. On the hands,
      the index finger was the most affected. Mycosis exams were not requested for all
      clinically suspected cases. When exams were done, results showed that the most
      common fungus was Trichophyton rubrum. The most common clinical lesion was distal
      lateral. The most prescribed topical treatments were amorolfine and ciclopirox
      olamine, while systemic treatments included fluconazole and terbinafine.
      CONCLUSION: This study was important to describe the epidemiological behavior of
      onychomycosis in Brazilian dermatology offices and to determine important risk
      factors, such as gender, age, practice of exercises, personal history of the
      disease, and comorbidities.

PMID- 23539066
TI  - Assessing findings from the fast track study.
AB  - OBJECTIVES: The aim of this paper is to respond to the Commentary, "Reassessing
      Findings from the Fast Track Study: Problems of Methods and Analysis" provided by
      E. Michael Foster (Foster, this issue) to our article "Fast Track Intervention
      Effects on Youth Arrests and Delinquency" (Conduct Problems Prevention Research
      Group 2010, Journal of Experimental Criminology, 6, 131-157). Our response begins
      with a description of the mission and goals of the Fast Track project, and how
      they guided the original design of the study and continue to inform outcome
      analyses. Then, we respond to the Commentary's five points in the order they were
      raised. CONCLUSIONS: We agree with the Commentary that efforts to prevent crime
      and delinquency are of high public health significance because the costs of crime
      and delinquency to society are indeed enormous. We believe that rigorous, careful
      intervention research is needed to accumulate evidence that informs prevention
      programs and activities. We have appreciated the opportunity to respond to the
      Commentary and to clarify the procedures and results that we presented in our
      paper on Fast Track effects on youth arrests and delinquency. Our response has
      clarified the framework for the number of statistical tests made, has reiterated
      the randomization process, has supported our tests for site-by-intervention
      effects, has provided our rationale for assuming missing at random, and has
      clarified that the incarceration variable was not included as a covariate in the
      hazard analyses. We stand by our conclusion that random assignment to Fast Track
      had a positive impact in preventing juvenile arrests, and we echo our additional
      caveat that it will be essential to determine whether intervention produces any
      longer-term effects on adult arrests as the sample transitions into young
      adulthood. We also appreciate the opportunity for open scientific debate on the
      values and risks associated with multiple analyses in long-term prevention
      program designs such as Fast Track. We believe that, once collected, completed
      longitudinal intervention datasets should be fully used to understand the impact,
      process, strengths, and weaknesses of the intervention approach. We agree with
      the Commentary that efforts to prevent crime and delinquency are of high public
      health significance because the costs of crime and delinquency to society are
      indeed enormous. As a result, we argue that it is important to balance the need
      to maintain awareness and caution regarding potential risks in the design or
      approach that may confound interpretation of findings, in the manner raised by
      the Commentator, with the need for extended analyses of the available data so we
      can better understand over time how antisocial behavior and violence can be
      effectively reduced.

PMID- 23539067
TI  - Endovascular repair with chimney technique of abdominal aortic aneurysm with
      hostile aortic neck.
AB  - Abdominal aortic aneurysm (AAA) with hostile aortic neck is not a good candidate
      for conventional endovascular aneurysm repair (EVAR), and a recent paper showed
      that EVAR with chimney technique (Ch-EVAR) yielded reasonable outcome. We report
      here a case of successful Ch-EVAR treatment of AAA with hostile neck. An 81-year
      old man presented with a 71-mm AAA during evaluation of a gastric ulcer. Aortic
      neck was 30 mm in diameter, 10-15 mm in length and angulated by 100 degrees .
      EVAR was performed with chimney stenting to both renal arteries, and the patient
      recovered after transient hematuria. At one-year follow-up, AAA had increased by
      7 mm with delayed type I endoleak control without renal insufficiency. The
      patient needed close follow-up. 

PMID- 23539068
TI  - Internal carotid artery redundancy and dissection  in a young cocaine abuser.
AB  - Carotid artery redundancies are common findings on routine imaging studies and
      are usually considered to be benign variants. We present a case of a 40-year-old
      man, with a history of cocaine abuse, who was diagnosed with dissection of the
      right internal carotid artery and looping of the bilateral internal carotid
      arteries. This report attempts to highlight the possible association between
      carotid artery redundancy and dissection, especially in the context of vascular
      injury such as cocaine abuse, as in our case.

PMID- 23539069
TI  - Successful endovascular extraction of newer generation Angio-Seal collagen plug
      and anchor after acute embolization.
AB  - A 75-year-old woman with past medical history of coronary bypass, atrial
      fibrillation, mitral valve repair undergoes percutaneous coronary intervention of
      left circumflex artery with a drug eluting stent. An Anglo-Seal vascular closure
      device was used post procedure to obtain hemostasis. Shortly after deployment,
      frank bleeding was observed necessitating manual compression at the arteriotomy
      site. After hemostasis was achieved, the right lower extremity was found to be
      pale, bluish with feeble pulses. Doppler ultrasound was emergently performed
      revealing decreased blood flow after mid superficial femoral artery (SFA) and an
      echo lucent object lodged luminally in the SFA. Patient was urgently taken to the
      vascular laboratory where an Angio-Seal device, including the collagen plug and
      anchor, was successfully removed endovascularly patient made full recovery and
      was discharged home the following day.

PMID- 23539070
TI  - Long-term outcome in patients with obscure gastrointestinal bleeding after
      negative capsule endoscopy.
AB  - AIM: To investigate long-term outcome in obscure gastrointestinal bleeding (OGIB)
      after negative capsule endoscopy (CE) and identify risk factors for rebleeding.
      METHODS: A total of 113 consecutive patients underwent CE for OGIB from May 2003
      to June 2010 at Seoul National University Hospital. Ninety-five patients (84.1%)
      with a subsequent follow-up after CE of at least 6 mo were enrolled in this
      study. Follow-up data were obtained from the patients' medical records. The CE
      images were reviewed by two board-certified gastroenterologists and consensus
      diagnosis was used in all cases. The primary outcome measure was the detection of
      rebleeding after CE, and factors associated with rebleeding were evaluated using
      multivariate analysis. RESULTS: Of the 95 enrolled patients (median age 61 years,
      range 17-85 years), 62 patients (65.3%) were male. The median duration of follow
      up was 23.7 mo (range 6.0-89.4 mo). Seventy-three patients (76.8%) underwent CE
      for obscure-overt bleeding. Complete examination of the small bowel was achieved
      in 77 cases (81.1%). Significant lesions were found in 38 patients (40.0%). The
      overall rebleeding rate was 28.4%. The rebleeding rate was higher in patients
      with positive CE (36.8%) than in those with negative CE (22.8%). However, there
      was no significant difference in cumulative rebleeding rates between the two
      groups (log rank test; P = 0.205). Anticoagulation after CE examination was an
      independent risk factor for rebleeding (hazard ratio, 5.019; 95%CI, 1.560-16.145;
      P = 0.007), regardless of CE results. CONCLUSION: Patients with OGIB and negative
      CE have a potential risk of rebleeding. Therefore, close observation is required
      and alternative modalities should be considered in suspicious cases.

PMID- 23539071
TI  - Uterine intravenous leiomyomatosis with cardiac extension: Imaging
      characteristics and literature review.
AB  - Intravenous leiomyomatosis (IVL), showing unusual growth patterns of uterine
      leiomyoma, is a rare neoplasm characterized by intravascular proliferation of a
      histologically benign-looking smooth muscle cell tumor mass, but not invading the
      tissue. To date, less than 300 cases have been reported and fewer than 100 cases
      with cardiac involvement. Imaging characteristics of IVL are still not clear so
      it is usually misdiagnosed before surgery. A 36-year-old woman, who had undergone
      hysterectomy due to hysteromyoma, presented with shortness of breath after
      activities. Imaging showed IVL with mass involvement of the left ovarian vein,
      left renal vein, left external and common iliac vein, as well as within the
      inferior vena cava (IVC), extending into the right atrium. The operation
      demonstrated that the mass had no stalk and had well-demarcated borders with the
      wall of the right atrium and IVC. The patient underwent a one-stage combined
      multidisciplinary thoraco-abdominal operation under general anesthetic.
      Subsequently, the pathology report confirmed IVL. IVL should be considered in a
      female patient presenting with an extensive mass in the right side of the heart.
      Imaging technology, such as echocardiogram, contrast-enhanced computed tomography
      and magnetic resonance imaging, can provide important information to reveal the
      mass, the range and path of the lesion, and relates to the surgical plan
      decision. Consequently, perfect and exact image examination is very necessary pre
      operation.

PMID- 23539072
TI  - Conjugation to Biocompatible Dendrimers Increases Lanthanide T2 Relaxivity of
      Hydroxypyridinone (HOPO) Complexes for Magnetic Resonance Imaging (MRI).
AB  - Magnetic resonance imaging (MRI) contrast agents represent a worldwide billion
      dollar market annually. While T1 relaxivity enhancement contrast agents receive
      greater attention and a significantly larger market share, the commercial
      potential for T2 relaxivity enhancing contrast agents remains a viable diagnostic
      option due to their increased relaxivity at high field strengths. Improving the
      contrast and biocompatibility of T2 MRI probes may enable new diagnostic
      prospects for MRI. Paramagnetic lanthanides have the potential to decrease T1 and
      T2 proton relaxation times, but are not commercially used in MRI diagnostics as
      T2 agents. In this article, oxygen donor chelates (hydroxypyridinone, HOPO, and
      terephthalamide, TAM) of various lanthanides are demonstrated as biocompatible
      macromolecular dendrimer conjugates for the development of T2 MRI probes. These
      conjugates have relaxivities up to 374 mm-1s-1 per dendrimer, high
      bioavailability, and low in vitro toxicity.

PMID- 23539074
TI  - CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian
      cancer - CA19-9 level in teratoma.
AB  - BACKGROUND: We aimed to identify clinical characteristics of ovarian mature
      cystic teratoma (MCT) in association with CA19-9 elevation, and to determine if
      CA19-9 is a useful marker in discrimination of MCT from ovarian cancer (OC).
      MATERIAL AND METHODS: Medical records of 322 women with pathologically-confirmed
      MCT or OC (stage 1 or 2) were reviewed retrospectively. The relationships between
      the characteristics of MCT (mean diameter, bilaterality, and pathologic
      components) and elevated CA19-9 were evaluated. Tumor markers in MCT were
      compared to those in OC. RESULTS: MCTs with CA19-9 elevation were correlated with
      a larger diameter (8.53+/-3.84 cm vs. 6.95+/-3.97 cm, p=0.002) and presence of
      fat component (67.1% vs. 32.9%, p<0.001), compared to those with normal CA 19-9.
      Although the incidence of CA19-9 elevation was not different between patients
      with MCT and OC (p=0.700), the mean value of CA19-9 was higher in those with OC
      (114.66+/-20.66 U/mL vs. 508.58+/-261.63 U/mL, p=0.013). In addition,
      simultaneous elevation of CA125 and CA19-9 was associated with a higher
      probability of malignant neoplasm (p<0.001; odds ratio: 23.7; 95% confidence
      interval: 8.863-63.576) than single elevation of CA 19-9. CONCLUSIONS: CA19-9
      could be an important tool in the diagnosis of ovarian mature cystic teratoma.
      CA19-9, in combination with CA125, might be a useful marker in discrimination of
      MCT from cancer.

PMID- 23539073
TI  - Influence of Kupffer cells and platelets on ischemia-reperfusion injury in mild
      steatotic liver.
AB  - AIM: To investigate the effect of mild steatotic liver on ischemia-reperfusion
      injury by focusing on Kupffer cells (KCs) and platelets. METHODS: Wistar rats
      were divided into a normal liver group (N group) and a mild steatotic liver group
      (S group) induced by feeding a choline-deficient diet for 2 wk. Both groups were
      subjected to 20 min of warm ischemia followed by 120 min of reperfusion. The
      number of labeled KCs and platelets in sinusoids and the blood perfusion in
      sinusoids were observed by intravital microscopy (IVM), which was performed at
      30, 60 and 120 min after reperfusion. To evaluate serum alanine aminotransferase
      as a marker of liver deterioration, blood samples were taken at the same time as
      IVM. RESULTS: In the S group, the number of platelets adhering to KCs decreased
      significantly compared with the N group (120 after reperfusion; 2.9 +/- 1.1
      cells/acinus vs 4.8 +/- 1.2 cells/acinus, P < 0.01). The number of KCs in
      sinusoids was significantly less in the S group than in the N group throughout
      the observation periods (before ischemia, 19.6 +/- 3.3 cells/acinus vs 28.2 +/-
      4.1 cells/acinus, P < 0.01 and 120 min after reperfusion, 29.0 +/- 4.3
      cells/acinus vs 40.2 +/- 3.3 cells/acinus, P < 0.01). The blood perfusion of
      sinusoids 120 min after reperfusion was maintained in the S group more than in
      the N group. Furthermore, elevation of serum alanine aminotransferase was lower
      in the S group than in the N group 120 min after reperfusion (99.7 +/- 19.8 IU/L
      vs 166.3 +/- 61.1 IU/L, P = 0.041), and histological impairment of hepatocyte
      structure was prevented in the S group. CONCLUSION: Ischemia-reperfusion injury
      in mild steatotic liver was attenuated compared with normal liver due to the
      decreased number of KCs and the reduction of the KC-platelet interaction.

PMID- 23539075
TI  - Effect of ACTN3 gene on strength and endurance in soccer players.
AB  - Sports efficiency in activities in which strength and speed are the determining
      factors has been associated to the ACTN3 gene, which is responsible for the
      expression of alpha-actinin-3. Soccer is a mainly aerobic sport because of its
      long duration, but the acute actions that define the game demand a lot of
      strength and speed. The purpose of the present study was to compare the
      performance capacity of soccer players with different genotype groups of ACTN3
      (XX, RX, and RR) in strength, speed, and endurance tests. Two hundred
      professional players of Brazilian soccer first division teams participated in
      this study. Speed, jump, and endurance test results were compared with the
      polymorphisms of the ACTN3 gene. It was noticed that RR individuals spent less
      time to run a 10-m path, compared with XX individuals (p < 0.05). The RR
      individuals also presented lower time rates at the 20- and 30-m path, compared
      with RX and XX individuals (p < 0.05). In jump tests, RR individuals presented
      higher rates, compared with RX and XX individuals (p < 0.05). As for aerobic
      tests, the XX individuals presented higher rates of V[Combining Dot Above]O2 max,
      compared with the RR group (p < 0.05), and did not differ from the RX group. The
      main conclusion of this study is that soccer players of genotype ACTN3/RR are the
      fastest in short distances and present higher jump potential. ACTN3/XX
      individuals presented the highest aerobic capacity. These findings can be used in
      training load adjustment and can influence the development of tactical schemes in
      soccer matches.

PMID- 23539076
TI  - Effect of cold conditions on double poling sprint performance of well-trained
      male cross-country skiers.
AB  - This study compared the effects of cold (-14 degrees  C) and moderate
      environments (6 degrees  C) on double poling (DP) sprint performance. Wearing
      modern cross-country ski racing suits, 14 highly trained male cross-country
      skiers performed a test protocol on a DP ergometer, consisting of a standardized
      warm-up followed by a 30-second maximal sprint (DP30s) and a 2-minute maximal
      sprint (DP2min), and after an 8-minute recovery period, another DP30s and DP2min
      were performed. Finally, the participants performed an incremental DP test to
      exhaustion. We observed no difference between rectal temperature in cold and
      moderate conditions. Mean skin temperature (Tskin) was lower in the cold
      condition; the lowest values being 20.3 degrees  C at -14 degrees  C and 27.0
      degrees  C at 6 degrees  C. Power output decreased between the first and the
      second DP30s under both conditions, but the reduction was 4.9% (p < 0.05) greater
      in the cold condition. Power output decreased by 4.8% (p < 0.05) between the
      first and second DP2min at -14 degrees  C, but we found no difference at 6
      degrees  C. In the incremental test to exhaustion, there was a 7.2% (p < 0.05)
      reduction in peak power output and a 7.8% (p < 0.05) lower peak oxygen
      consumption at -14 degrees  C. In conclusion, this study demonstrated that DP
      sprint performance was lower at -14 degrees  C than at 6 degrees  C. Tskin and
      body temperature were lower at -14 degrees  C. This may indicate cooling of
      superficial musculature and may explain the reduced DP sprint performance
      observed in our study.

PMID- 23539077
TI  - Anthropometric profile and body composition of Irish adolescent rugby union
      players aged 16-18.
AB  - The literature suggests that one of the key determinants of success at rugby
      union international competitions is the anthropometric profile of players. The
      Irish Rugby Football Union (IRFU) long-term player development (LTPD) model is a
      framework designed to guide the development of the tactical, physical, and
      psychological domains of sporting participation. In Ireland, the Train-to-Train
      stage of the IRFU model is a critical stage, whereby the next developmental
      progression would include the transition of players into professional academies.
      To date, no previously published studies have examined the anthropometric profile
      of Irish Schools' rugby union players at the Train-to-Train stage of the IRFU
      model. The anthropometric profile of 136 male adolescent rugby union players at
      the Train-to-Train stage of the IRFU model was assessed using total-body dual
      energy x-ray absorptiometry. Significant differences in height, body mass, body
      fat percentage, fat mass, lean mass, and fat-free mass were observed between
      players assigned to the forward and back units, and for specific position
      categorizations within each unit. Direct logistic regression revealed that body
      mass was a statistically significant (p < 0.01) predictor of unit position
      classification, with an odds ratio of 2.35, indicating that the players with a
      higher body mass were twice as likely to be classified as forwards. The results
      of this study indicate that at the Train-to-Train stage of the IRFU model,
      forward and back units have distinctly different anthropometric profiles.
      Furthermore, anthropometric differentiation also exists within specific position
      categorizations within each of these playing units. Thus, anthropometric
      profiling should be carried out on a systematic and periodic basis, because this
      will allow for the evaluation of the effectiveness of the implementation
      strategies of the IRFU model on a national basis.

PMID- 23539078
TI  - Neuromuscular responses during aquatic resistance exercise with different devices
      and depths.
AB  - Little research has been reported regarding the effects of using different
      devices and immersion depths during the performance of resistance exercises in a
      water environment. The purpose of this study was to compare muscular activation
      of upper extremity and core muscles during shoulder extensions performed at
      maximum velocity with different devices and at different depths. Volunteers (N =
      24) young fit male university students performed 3 repetitions of shoulder
      extensions at maximum velocity using 4 different devices and at 2 different
      depths. The maximum amplitude of the electromyographic root mean square of the
      latissimus dorsi (LD), rectus abdominis, and erector lumbar spinae was recorded.
      Electromyographic signals were normalized to the maximum voluntary isometric
      contraction. No significant (p > 0.05) differences were found in the
      neuromuscular responses between the different devices used during the performance
      of shoulder extension at xiphoid process depth. Regarding the comparisons of
      muscle activity between the 2 depths analyzed in this study, only the LD showed a
      significantly (p <= 0.05) higher activity at the xiphoid process depth compared
      with that at the clavicle depth. Therefore, if maximum muscle activation of the
      extremities is required, the xiphoid depth is a better choice than clavicle
      depth, and the kind of device is not relevant. Regarding core muscles, neither
      the kind of device nor the immersion depth modifies muscle activation.

PMID- 23539079
TI  - Effects of weighted sled towing with heavy versus light load on sprint
      acceleration ability.
AB  - Weighted sled towing is used by athletes to improve sprint acceleration ability.
      The typical coaching recommendation is to use relatively light loads, as
      excessively heavy loads are hypothesized to disrupt running mechanics and be
      detrimental to sprint performance. However, this coaching recommendation has not
      been empirically tested. This study compared the effects of weighted sled towing
      with 2 different external loads on sprint acceleration ability. Twenty-one
      physically active men were randomly allocated to heavy- (n = 10) or light-load
      weighted sled towing (n = 11) groups. All subjects participated in 2 training
      sessions per week for 8 weeks. The subjects in the heavy and light groups
      performed weighted sled towing using external loads that reduced sprint velocity
      by approximately 30 and 10%, respectively. Before and after the training, the
      subjects performed a 10-m sprint test, in which split time was measured at 5 and
      10 m from the start. The heavy group significantly improved both the 5- and 10-m
      sprint time by 5.7 +/- 5.7 and 5.0 +/- 3.5%, respectively (P < 0.05), whereas
      only 10-m sprint time was improved significantly by 3.0 +/- 3.5% (P < 0.05) in
      the light group. No significant differences were found between the groups in the
      changes in 5-m and 10-m sprint time from pre- to posttraining. These results
      question the notion that training loads that induce greater than 10% reduction in
      sprint velocity would negatively affect sprint performance and point out the
      potential benefit of using a heavier load for weighted sled towing.

PMID- 23539080
TI  - Effects of a 10-week resistance exercise program on soccer kick biomechanics and
      muscle strength.
AB  - The purpose of the study was to examine the effects of a resistance exercise
      program on soccer kick biomechanics. Twenty male amateur soccer players were
      divided in the experimental group (EG) and the control group (CG), each
      consisting of 10 players. The EG followed a 10-week resistance exercise program
      mainly for the lower limb muscles. Maximal instep kick kinematics,
      electromyography, and ground reaction forces (GRFs) as well as maximum isometric
      leg strength were recorded before and after training. A 2-way analysis of
      variance showed significantly higher ball speed values only for the EG (26.14 +/-
      1.17 m.s vs. 27.59 +/- 1.49 m.s before and after training, respectively), whereas
      no significant differences were observed for the CG. The EG showed a decline in
      joint angular velocities and an increase in biceps femoris electromyography of
      the swinging leg during the backswing phase followed by a significant increase in
      segmental and joint velocities and muscle activation of the same leg during the
      forward swing phase (p < 0.05). The EG also showed significantly higher vertical
      GRFs and rectus femoris and gastrocnemius activation of the support leg (p <
      0.05). Similarly, maximum and explosive isometric force significantly increased
      after training only for the EG (p < 0.05). These results suggest that increases
      in soccer kicking performance after a 10-week resistance training program were
      accompanied by increases in maximum strength and an altered soccer kick movement
      pattern, characterized by a more explosive backward-forward swinging movement and
      higher muscle activation during the final kicking phase.

PMID- 23539081
TI  - Skating crossovers on a motorized flywheel: a preliminary experimental design to
      test effect on speed and on crossovers.
AB  - Ice hockey requires frequent skater crossovers to execute turns. Our
      investigation aimed to determine the effectiveness of training crossovers on a
      motorized, polyethylene high-resistance flywheel. We hypothesized that high
      school hockey players training on the flywheel would perform as well as their
      peers training on ice. Participants were 23 male high-school hockey players (age
      15-19 years). The study used an experimental prospective design to compare
      players who trained for 9 sessions on the 22-foot flywheel with players who
      trained for 9 sessions on a similarly sized on-ice circle. Both groups were
      compared with control subjects who were randomly selected from the same
      participant pool as those training on ice. All players were tested before and
      after their 3-week training regimens, and control subjects were asked to not
      practice crossovers between testing. Group 1 trained in a hockey training
      facility housing the flywheel, and group 2 trained in the ice hockey arena where
      testing occurred. Primary outcome measures tested in both directions were: (a)
      speed (time in seconds) required to skate crossovers for 3 laps of a marked face
      off circle, (b) cadence of skating crossovers on the similarly sized circles, and
      (c) a repeat interval speed test, which measures anaerobic power. No significant
      changes were found between groups in on-ice testing before and after training.
      Among the group 1 players, 7 of 8 believed they benefited from flywheel training.
      Group 2 players, who trained on ice, did not improve performance significantly
      over group 1 players. Despite the fact that no significant on-ice changes in
      performance were observed in objective measures, players who trained on the
      flywheel subjectively reported that the flywheel is an effective cost-effective
      alternative to training on ice. This is a relevant finding when placed in context
      with limited availability of on-ice training.

PMID- 23539082
TI  - Quantification of the relative age effect in three indices of physical
      performance.
AB  - The relative age effect (RAE) describes the relationship between an individual's
      birth month and their level of attainment in sports. There is a clustering of
      birth dates just after the cutoff used for selection in age-grouped sports, and
      it is hypothesized that such relatively older sportspeople may enjoy maturational
      and physical advantages over their younger peers. There is, however, little
      empirical evidence of any such advantage. This study investigated whether
      schoolchildren's physical performance differed according to which quarter of the
      school year they were born in. Mass, stature, body mass index, cardiorespiratory
      fitness, strength, and power were measured in 10 to 16 year olds (n = 8,550, 53%
      male). We expressed test performance as age- and sex-specific z-scores based on
      reference data with age rounded down to the nearest whole year and also as units
      normalized for body mass. We then compared these values between yearly birth
      quarters. There were no significant main effects for differences in
      anthropometric measures in either sex. Girls born in the first quarter of the
      school year were significantly stronger than those born at other times when
      handgrip was expressed as a z-score. As z-scores, all measures were significantly
      higher in boys born in either the first or second yearly quarters. Relative to
      body mass, cardiorespiratory fitness was higher in boys born in the first quarter
      and power was higher in those born in the second quarter. The RAE does not appear
      to significantly affect girls' performance test scores when they are expressed as
      z-score or relative to body mass. Boys born in the first and second quarters of
      the year had a significant physical advantage over their relatively younger
      peers. These findings have practical bearing if coaches use fitness tests for
      talent identification and team selection. Categorizing test performance based on
      rounded down values of whole-year age may disadvantage children born later in the
      selection year. These relatively younger children may be less to gain selection
      for teams or training programmes.

PMID- 23539083
TI  - Effect of an aerodynamic helmet on head temperature, core temperature, and
      cycling power compared with a traditional helmet.
AB  - Nonvented "aerodynamic helmets" reduce wind resistance but may increase head (Th)
      and gastrointestinal (Tgi) temperature and reduce performance when worn in hot
      conditions. This study tested the hypothesis that Th and Tgi would be greater
      during low-intensity cycling (LIC) in the heat while wearing an aero helmet
      (AERO) vs. a traditional vented racing helmet (REG). This study also tested the
      hypothesis that Th, Tgi, and finish time would be greater, and power output would
      be reduced during a self-paced time trial in the heat with AERO vs. REG. Ten
      highly trained heat-acclimated endurance athletes conducted LIC (50% V[Combining
      Dot Above]O2max, LIC) and a high-intensity 12-km self-paced time trial (12-km TT)
      on a cycle ergometer in 39 degrees  C on 2 different days (AERO and REG),
      separated by >48 hours. During LIC, Th was higher at minute 7.5 and all time
      points thereafter in AERO vs. REG (p < 0.05). Similarly, during the 12-km TT, Th
      was higher at minutes 12.5, 15, and 17.5 in AERO vs. REG (p < 0.05). Heart rate
      (HR) and Tgi increased during LIC and during 12-km TT (both p < 0.001); however,
      no significant interaction (helmet * time) existed for HR or Tgi at either
      intensity (all p > 0.05). No group differences existed for finish time or power
      output during the 12-km TT (both p > 0.05). In conclusion, Th becomes elevated
      during cycling in the heat with an aero helmet compared with a traditional vented
      racing helmet during LIC and high-intensity cycling, yet Tgi and HR responses are
      similar irrespective of helmet type and Th. Furthermore, the higher Th that
      develops when an aero helmet is worn during cycling in the heat does not affect
      power output or cycling performance during short-duration high-intensity events.

PMID- 23539084
TI  - Physical performance profile of handball players is related to playing position
      and playing class.
AB  - The purpose of the study was to compare anthropometric data and physical
      performance characteristics between different playing positions in professional
      team handball. Furthermore, a comparison between performance profiles of first
      and second division players was made. Thirty-four male professional handball
      players were recruited. Measurement of heart rates (HRs) during official games
      anthropometric data, sprint ability, jumping performance, throwing velocity, and
      endurance performance were determined and analyzed with respect to playing
      position. In a further step, additional 31 players from German second division
      were recruited to compare their profile on each position with profile of the
      first division players. Players of wings and backs positions had highest average
      HRs during game, best times in 30-m sprint tests, best jumping performance, and
      best anaerobic endurance performance. Similarly, backs and wings reached highest
      throwing velocities. Regarding anthropometric characteristics, wings were players
      with lowest body height and weight, whereas pivots were heaviest players and
      players with highest body mass index (BMI). We further found that wings from
      first division had a better sprint performance compared with wings from second
      division. Furthermore, pivots from first division had higher BMI and drop jump
      performance. Our data demonstrated a close relationship of anthropometric data,
      physical performance characteristic, and the playing position of handball. These
      information might be helpful for the assessment and evaluation of talents and may
      help to develop and optimize position-specific training regimes and
      identification of talents.

PMID- 23539085
TI  - Neuromuscular function, hormonal, and mood responses to a professional rugby
      union match.
AB  - We examined the recovery time-course of neuromuscular function (NMF), the
      testosterone and cortisol hormonal milieu, and mood for 60 hours after a
      competitive match in professional rugby union players (n = 14). Thirty-six hours
      prematch (19:30 hours kick-off), baseline saliva samples (testosterone, cortisol,
      and testosterone to cortisol [T/C] ratio), countermovement jump performances
      (peak power output [PPO]), and mood disruption (Brief Assessment of Mood
      Questionnaire) were collected and was repeated at 12, 36, and 60 hours postmatch.
      Peak power output decreased below baseline at 12 hours (baseline 6,100 +/- 565 W
      vs. 12 h 5,680 +/- 589 W; p = 0.004) and 36 hours (5,761 +/- 639 W; p < 0.001)
      but had recovered at 60 hours (5,950 +/- 505 W; p = 0.151). Cortisol
      concentrations increased from baseline at 12 hours (baseline 0.40 +/- 0.09 ug.dl
      1 vs. 12 h 0.60 +/- 0.20 ug.dl-1; p = 0.004) and 36 hours (0.60 +/- 0.20 ug.dl-1;
      p = 0.027) but were similar at 60 hours postmatch. Testosterone concentrations
      decreased from baseline at 12 hours (baseline 214 +/- 84 pg.ml-1 vs. 12 h 151 +/-
      56 pg.ml-1; p = 0.023) and 36 hours (173 +/- 71 pg.ml-1; p = 0.016) but were
      similar at 60 hours postmatch. The T/C ratio decreased from baseline at 12 hours
      (baseline 551 +/- 219 vs. 12 h 266 +/- 123; p = 0.001) and 36 hours (310 +/- 148;
      p = 0.027) before returning to baseline at 60 hours postmatch. Mood disturbance
      increased at 12 hours (p = 0.031) before returning to baseline at 36 and 60 hours
      postmatch. There were no relationships between changes in PPO, testosterone,
      cortisol, T/C ratio, and mood. In conclusion, postmatch changes in NMF, salivary
      hormones, and mood disturbance were identified in professional rugby union
      players. Players and coaches can expect reduced NMF and hormonal disruption for
      36 hours before recovering at 60 hours postmatch, with mood recovered by 36 hours
      postmatch. Knowledge of these recovery time-courses may prove useful for player
      training program design and postmatch recovery strategies.

PMID- 23539086
TI  - Fine mapping of qhir1 influencing in vivo haploid induction in maize.
AB  - Production of haploids by the in vivo haploid induction method has now become
      routine for generating new inbred lines in maize. In previous studies, a major
      quantitative trait locus (QTL) (qhir1) located in bin 1.04 was detected,
      explaining up to 66 % of the genotypic variance for haploid induction rate (HIR).
      Our objectives were to (1) fine-map qhir1 and (2) identify closely linked markers
      useful for marker-assisted breeding of new inducers. For this purpose, we
      screened a mapping population of 14,375 F2 plants produced from a cross between
      haploid inducer UH400 and non-inducer line 1680 to identify recombinants. Based
      on sequence information from the B73 reference genome, markers polymorphic
      between the two parents were developed to conduct fine mapping with these
      recombinants. A progeny test mapping strategy was applied to accurately determine
      the HIR of the 14 recombinants identified. Furthermore, F3 progeny of recombinant
      F2 plants were genotyped and in parallel evaluated for HIR. We corroborated
      earlier studies in that qhir1 has both a significantly positive effect on HIR but
      also a strong selective disadvantage, as indicated by significant segregation
      distortion. Altogether, we were able to narrow down the qhir1 locus to a 243 kb
      region flanked by markers X291 and X263. 

PMID- 23539087
TI  - Complete mitochondrial genome sequence and identification of a candidate gene
      responsible for cytoplasmic male sterility in radish (Raphanus sativus L.)
      containing DCGMS cytoplasm.
AB  - A novel cytoplasmic male sterility (CMS) conferred by Dongbu cytoplasmic and
      genic male-sterility (DCGMS) cytoplasm and its restorer-of-fertility gene (Rfd1)
      was previously reported in radish (Raphanus sativus L.). Its inheritance of
      fertility restoration and profiles of mitochondrial DNA (mtDNA)-based molecular
      markers were reported to be different from those of Ogura CMS, the first reported
      CMS in radish. The complete mitochondrial genome sequence (239,186 bp; GenBank
      accession No. KC193578) of DCGMS mitotype is reported in this study. Thirty-four
      protein-coding genes and three ribosomal RNA genes were identified. Comparative
      analysis of a mitochondrial genome sequence of DCGMS and previously reported
      complete sequences of normal and Ogura CMS mitotypes revealed various recombined
      structures of seventeen syntenic sequence blocks. Short-repeat sequences were
      identified in almost all junctions between syntenic sequence blocks. Phylogenetic
      analysis of three radish mitotypes showed that DCGMS was more closely related to
      the normal mitotype than to the Ogura mitotype. A single 1,551-bp unique region
      was identified in DCGMS mtDNA sequences and a novel chimeric gene, designated
      orf463, consisting of 128-bp partial sequences of cox1 gene and 1,261-bp
      unidentified sequences were found in the unique region. No other genes with a
      chimeric structure, a major feature of most characterized CMS-associated genes in
      other plant species, were found in rearranged junctions of syntenic sequence
      blocks. Like other known CMS-associated mitochondrial genes, the predicted gene
      product of orf463 contained 12 transmembrane domains. Thus, this gene product
      might be integrated into the mitochondrial membrane. In total, the results
      indicate that orf463 is likely to be a casual factor for CMS induction in radish
      containing the DCGMS cytoplasm. 

PMID- 23539089
TI  - Chemical Stability of the Lipid Phase in Concentrated Beverage Emulsions Colored
      with Natural beta-Carotene.
AB  - The aim of this study was to examine the oxidation of selected plant oils in
      concentrated beverage emulsions colored with natural beta-carotene. Carotenoid
      preparations obtained from carrots were dissolved in cold-pressed linseed oil,
      refined canola oil, and refined palm olein. Oxidative stability of the lipids was
      examined with and without addition of the pigment to the oil/water (O/W)
      emulsion. Carotenoid/lipid hydro peroxide (LOOH) concentration was evaluated
      using two different methods: LOOH + Fe2+ reaction connected with a colored
      complex of ammonium thiocyanate determined with the help of a spectrophotometer,
      and LOOH determined with the help of a chemiluminometer. It was shown that
      oxidation rate of lipids in the O/W emulsions strongly depended on chemical
      composition of the lipid fraction (type of oil used). Presence of the carotenoid
      pigment increased the rate. Therefore, if a carotenoid-containing emulsion is to
      be stable, it should be based on oils of a high oxidative stability.

PMID- 23539088
TI  - A working memory model for serial order that stores information in the intrinsic
      excitability properties of neurons.
AB  - Models for temporary information storage in neuronal populations are dominated by
      mechanisms directly dependent on synaptic plasticity. There are nevertheless
      other mechanisms available that are well suited for creating short-term memories.
      Here we present a model for working memory which relies on the modulation of the
      intrinsic excitability properties of neurons, instead of synaptic plasticity, to
      retain novel information for periods of seconds to minutes. We show that it is
      possible to effectively use this mechanism to store the serial order in a
      sequence of patterns of activity. For this we introduce a functional class of
      neurons, named gate interneurons, which can store information in their membrane
      dynamics and can literally act as gates routing the flow of activations in the
      principal neurons population. The presented model exhibits properties which are
      in close agreement with experimental results in working memory. Namely, the
      recall process plays an important role in stabilizing and prolonging the memory
      trace. This means that the stored information is correctly maintained as long as
      it is being used. Moreover, the working memory model is adequate for storing
      completely new information, in time windows compatible with the notion of "one
      shot" learning (hundreds of milliseconds).

PMID- 23539090
TI  - Tonic spasms are a common clinical manifestation in patients with neuromyelitis
      optica.
AB  - Tonic spasms have been most commonly associated with multiple sclerosis. To date,
      few reports of series of patients with neuromyelitis optica and tonic spasms have
      been published. METHODS: We analyzed the characteristics and frequency of tonic
      spasms in 19 subjects with neuromyelitis optica. Data was collected using a semi
      structured questionnaire for tonic spasms, by both retrospectively reviewing
      medical records and performing clinical assessment. RESULTS: All patients except
      one developed this symptom. The main triggering factors were sudden movements and
      emotional factors. Spasms were commonly associated to sensory disturbances and
      worsened during the acute phases of the disease. Carbamazepine was most commonly
      used to treat the symptom and patients showed good response to the drug.
      CONCLUSIONS: Tonic spasms are a common clinical manifestation in patients with
      neuromyelitis optica.

PMID- 23539091
TI  - Trigger factors mainly from the environmental type are reported by adolescents
      with migraine.
AB  - Migraine can be triggered by many factors such as stress, sleep, fasting and
      environmental causes. There are few studies that evaluated migraine trigger
      factors in the adolescent population. METHODS: A total of 100 participants from
      10 to 19 years were subjected to a detailed headache questionnaire, with
      demographic and clinical data, and a headache diary including trigger factors
      during a two-month period was asked. RESULTS: Fifty of the participants exhibited
      chronic migraine and the other 50 participants demonstrated episodic migraine.
      The most common group of trigger factors reported was the environmental one,
      mainly sun/clarity, followed by hot weather and the smell of perfume.
      CONCLUSIONS: Ninety-one percent of children and adolescents with migraine
      reported a trigger factor precipitating the migraine attack.

PMID- 23539092
TI  - In their own voices: Latinas' experiences with a randomized controlled trial.
AB  - We conducted exit interviews with a random sample of 39 predominantly Central
      American immigrant mothers who had completed a longitudinal randomized controlled
      trial to prevent perinatal depression. We found that rates and levels of
      perinatal depression in the intervention and control groups were lower than
      expected and did not differ between groups at 1 year postpartum. Therefore, we
      conducted extensive semistructured interviews to (a) understand why these high
      risk women had such low rates of major depressive episodes and depressive
      symptoms, and (b) determine if the mechanisms responsible for reductions in
      depression differed between the intervention and usual care groups. We discovered
      that the intervention group learned specific mood-management skills from their
      participation in the intervention, and that the control group experienced their
      participation in the study as a "low-dose" intervention. Our experience
      highlights the importance of conducting qualitative studies to understand
      quantitative outcomes of intervention studies.

PMID- 23539093
TI  - "Trouble won't last always": religious coping and meaning in the stress process.
AB  - Meaning-based coping, particularly religious coping, might lead to positive
      emotions in stressful situations. Religious coping is common among older adults.
      We explored the experience of religious coping, organizational religious
      affiliation, and one's relationship with God among older adults with advanced
      chronic illness and their caregivers. Research questions included: How is
      religious coping experienced in this context? How is a relationship with God
      experienced in coping? How is meaning experienced in this context? Brief
      qualitative interviews uncovered descriptions of experiences using the
      qualitative descriptive method. Three themes were identified: God is a provider,
      one's religion and relationship with God when coping are essential, and the God
      person relationship is intimate. Care recipients coped through their personal
      relationship with God, whereas caregivers coped through religious beliefs and
      support. Meaning was defined as purpose, responsibility, and duty.

PMID- 23539094
TI  - The experience of HIV diagnosis among Aboriginal people living with HIV/AIDS and
      depression.
AB  - In this article, we consider how the broad context of Aboriginal people's lives
      can shape their experience and understanding of their HIV diagnosis. We conducted
      interviews across Canada with 72 Aboriginal people living with HIV who also
      reported feelings of depression. Consistent with what has been found in previous
      studies, participants responded to their HIV diagnosis with shock, disbelief, and
      often anger. Prior depression, drug and alcohol use, multiple losses, stigma, and
      social isolation also shaped how participants experienced their diagnosis. We
      consider how the history of colonization of Aboriginal communities in Canada
      relates to the experience of HIV diagnosis, and end with a discussion of the
      service implications of our findings.

PMID- 23539095
TI  - REMUS100 AUV with an integrated microfluidic system for explosives detection.
AB  - Quantitating explosive materials at trace concentrations in real-time on-site
      within the marine environment may prove critical to protecting civilians,
      waterways, and military personnel during this era of increased threat of
      widespread terroristic activity. Presented herein are results from recent field
      trials that demonstrate detection and quantitation of small nitroaromatic
      molecules using novel high-throughput microfluidic immunosensors (HTMI) to
      perform displacement-based immunoassays onboard a HYDROID REMUS100 autonomous
      underwater vehicle. Missions were conducted 2-3 m above the sea floor, and no
      HTMI failures were observed due to clogging from biomass infiltration.
      Additionally, no device leaks were observed during the trials. HTMIs maintained
      immunoassay functionality during 2 h deployments, while continuously sampling
      seawater absent without any pretreatment at a flow rate of 2 mL/min. This 20-fold
      increase in the nominal flow rate of the assay resulted in an order of magnitude
      reduction in both lag and assay times. Contaminated seawater that contained 20
      175 ppb trinitrotoluene was analyzed.

PMID- 23539096
TI  - Analysis of triacylglycerol hydroperoxides in human lipoproteins by Orbitrap mass
      spectrometer.
AB  - Herein, we represent a simple method for the detection and characterization of
      molecular species of triacylglycerol monohydroperoxides (TGOOH) in biological
      samples by use of reversed-phase liquid chromatography with a LTQ Orbitrap XL
      mass spectrometer (LC/LTQ Orbitrap) via an electrospray ionization source. Data
      were acquired using high-resolution, high-mass accuracy in Fourier-transform
      mode. Platform performance, related to the identification of TGOOH in human
      lipoproteins and plasma, was estimated using extracted ion chromatograms with
      mass tolerance windows of 5 ppm. Native low-density lipoproteins (nLDL) and
      native high-density lipoproteins (nHDL) from a healthy donor were oxidized by
      CuSO4 to generate oxidized LDL (oxLDL) and oxidized HDL (oxHDL). No TGOOH
      molecular species were detected in the nLDL and nHDL, whereas 11 species of TGOOH
      molecules were detected in the oxLDL and oxHDL. In positive-ion mode, TGOOH was
      found as [M + NH4](+). In negative-ion mode, TGOOH was observed as [M + CH3COO](
      ). TGOOH was more easily ionized in positive-ion mode than in negative-ion mode.
      The LC/LTQ Orbitrap method was applied to human plasma and three molecular
      species of TGOOH were detected. The limit of detection is 0.1 pmol (S/N = 10:1)
      for each synthesized TGOOH.

PMID- 23539097
TI  - Recent advances in on-line concentration and separation of amino acids using
      capillary electrophoresis.
AB  - This article highlights recent methodological developments in the on-line
      concentration and separation of amino acids and their enantiomers using capillary
      electrophoresis. Sections are dedicated to recent contributions to on-line
      concentration strategies such as field-amplified sample stacking, large-volume
      sample stacking, dynamic pH junction, transient isotachophoresis, sweeping, and
      the combination of two methods. The main applications, advantages, and
      limitations of these procedures in the biological, food, and pharmaceutical
      fields are addressed. Comprehensive tables listing on-line techniques for the
      concentration and separation of amino acids and their enantiomers, categorized by
      the stacking strategies used, background electrolytes, sample matrix, limit of
      detection, and enhancement factor, are provided. 

PMID- 23539098
TI  - Enantioselective separation of amino acids as biomarkers indicating life in
      extraterrestrial environments.
AB  - Traces of prebiotic amino acids, i.e., the building blocks of proteins, are
      excellent biomarkers that could provide evidence of extinct or extant life in
      extra-terrestrial environments. In particular, characterization of the
      enantiomeric excess of amino acids gives relevant information about the biotic or
      abiotic origin of molecules, because it is generally assumed that life elsewhere
      could be based on either L or D amino acids, but not both. The analytical
      procedures used in in-situ space missions for chiral discrimination of amino
      acids must meet severe requirements imposed by flight conditions: short analysis
      time, low energy consumption, robustness, storage for long periods under extreme
      conditions, high efficiency and sensitivity, automation, and remote-control
      operation. Such methods are based on gas chromatography, high-pressure liquid
      chromatography, and capillary electrophoresis, usually coupled with mass
      spectrometry; of these, gas chromatography-mass spectrometry (GC-MS) is the only
      such combination yet used in space missions. Preliminary in-situ sample
      derivatization is required before GC-MS analysis to convert amino acids into
      volatile and thermally stable compounds. The silylation reagent most commonly
      used, N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide, is unsuitable for
      detection of homochirality, and alternative derivatization techniques have been
      developed that preserve the stereochemical configuration of the original
      compounds and are compatible with spaceflight conditions. These include the
      reagent N,N-dimethylformamide dimethylacetal, which has already been used in the
      Rosetta mission, a mixture of alkyl chloroformate, ethanol, and pyridine, a
      mixture of perfluorinated anhydrides and perfluoro alcohols, and
      hexafluoroacetone, the first gaseous derivatizing agent. In all the space
      instruments, solvent extraction of organic matter and chemical derivatization
      have been combined in a single automatic and remote-controlled procedure in a
      chemical reactor. Liquid-based separation systems have been used in space
      missions. In particular, microchip capillary electrophoresis, based on
      microfluidic lab-on-a-chip systems, enables high-performance chemical analysis of
      amino acids with low mass and volume equipment and low power and reagent
      consumption. Coupling with laser-induced fluorescence detectors results in ultra
      low limits of detection. This critical review describes applications of the on
      board instruments used in the Rosetta mission to comets and in the more recent
      Mars exploration program, i.e., the Mars Science Laboratory and ExoMars missions.

PMID- 23539099
TI  - Mass spectrometry imaging for biomedical applications.
AB  - The development of technologies for mass spectrometry imaging is of substantial
      research interest. Mass spectrometry is potentially capable of providing highly
      specific information about the distribution of compounds in tissues, with high
      sensitivity. The in-situ analysis needed for tissue imaging requires MS to be
      performed under conditions different from the traditional ones, typically with
      intensive sample preparation and optimized for pharmaceutical applications. In
      this paper we critically review the current status of MS imaging with different
      methods of sample ionization and discuss the 3D and quantitative imaging
      capabilities which need further development, the importance of the multi-modal
      imaging, and the balance between the pursuit of high-resolution imaging and the
      practical application of MS imaging in biomedicine. 

PMID- 23539100
TI  - Comparison of two different spectral domain optical coherence tomography devices
      in the detection of localized retinal nerve fiber layer defects.
AB  - PURPOSE: To compare the detection of localized retinal nerve fiber layer (RNFL)
      defects by two different spectral domain optical coherence tomography (SD-OCT)
      devices. METHODS: Eyes of 42 normal control subjects and 48 patients with a
      localized RNFL defect on red-free fundus photographs were imaged by the Cirrus
      (Carl Zeiss Meditec, Dublin, CA, USA) and 3D OCT (Topcon, Tokyo, Japan) devices.
      We compared sensitivities, specificities, and area under the receiver operating
      characteristic curves (AUCs) of circumpapillary RNFL (cpRNFL) thickness and
      ganglion cell complex (GCC) parameters between the two devices. RESULTS: The
      devices provided different cpRNFL thickness measurements. The highest
      sensitivities at fixed specificities of 80 % (Cirrus: 83.3 %; 3D OCT: 77.1 %) and
      95 % (Cirrus: 69.8 %; 3D OCT: 68.8 %) and the largest AUCs (Cirrus: 0.90; 3D OCT:
      0.88) obtained by the cpRNFL parameters of the two devices were similar. Based on
      the internal normative database, the deviation-from-normal map of the Cirrus OCT
      device and the 36-segment map of the 3D OCT device had the highest sensitivity
      (89.6 and 91.7 %, respectively). Among the macular GCC parameters of the 3D OCT
      device, inferior macular RNFL thickness had the highest sensitivity (81.2 % at a
      specificity of 80 %) and the largest AUC (0.89). CONCLUSIONS: Although the two SD
      OCT devices have different measurement protocols, they showed similar abilities
      for the detection of a localized RNFL defect.

PMID- 23539101
TI  - Death by insecticide.

PMID- 23539102
TI  - Judge tells committee it must reconsider its decision on Leeds paediatric heart
      unit.

PMID- 23539104
TI  - Australia exports an academic-powered news website to the UK.

PMID- 23539105
TI  - BMA calls for national launch of 111 urgent care hotline to be halted.

PMID- 23539106
TI  - [Guidelines for the diagnosis, prevention and treatment of osteoporosis. Italian
      Osteoporosis, Mineral Metabolism, and Skeletal Diseases Society].

PMID- 23539107
TI  - Biomarkers coding for ovPAG-1 mRNA expression and pregnancy status in Dohne
      Merino ewes at an abattoir.
AB  - The objective of the present study was to determine the pregnancy status of Dohne
      Merino ewes at slaughter. This was done by collecting blood samples from the ewes
      (n = 60) during exsanguination to assay for pregnancy biomarkers using radio
      immunological and TaqMan reverse transcription polymerase chain reaction
      techniques. The expressions of ovine pregnancy-associated glycoprotein within a
      range of 1.068(-09) to 8.977(-07) indicated 43.33 % ewes with pregnancy
      (DeltamRNA) signals at the point of slaughter. The assay validation showed that
      half of these ewes were truly pregnant, and most of the ewes that exhibited 'true
      positives' were within 56-60 kg live weight and were about 30 months old. The
      biomarkers used in this study, therefore, showed that approximately 22 % Dohne
      Merino ewes were truly pregnant at the point of slaughter.

PMID- 23539108
TI  - The use and reporting of patient-reported outcomes in phase III breast cancer
      trials.
AB  - BACKGROUND: Public and government attention to patient-centered research outcomes
      has been increasing, evidenced by the recent formation of the Patient Centered
      Outcomes Research Institute. Drug development clinical trials can be made more
      patient-centered by collecting patient-reported outcome measures that can inform
      decision making by patients and their health-care providers. Patient-reported
      outcomes are important to collect in trials of breast cancer therapeutics, which
      encompass a wide range of treatment regimens and side effects. PURPOSE: We sought
      to determine recent trends in the use of patient-reported outcomes in drug trials
      for the treatment of breast cancer and evaluate the reporting of these data in
      study publications. METHODS: We searched ClinicalTrials.gov for phase III breast
      cancer drug trials, recording information on start date, primary completion date,
      primary outcome measure, primary sponsor, stage of cancer, and patient-reported
      outcome use. To assess the reporting of patient-reported outcome data, Google.com
      and PubMed.gov were searched for all publications resulting from included trials.
      RESULTS: We found 236 eligible trials, starting between May 1989 and December
      2011. Of these trials, 83 (35%) stipulated patient-reported outcome use. The rate
      of patient-reported outcome use in recent years has shown no increase over
      earlier time periods: 37% (1989-2000) versus 36% (2004-2007) versus 30% (2008
      2011) (p = 0.8). Trials with sponsorship led by the pharmaceutical industry and
      trials including patients with locally advanced or metastatic disease had the
      highest rates of patient-reported outcome use (40/87 (46%) and 44/102 (43%),
      respectively). Among the 83 trials that collected patient-reported outcome
      measures, 36 were completed a minimum of 2 years before our analysis; of these 36
      studies, 19 (53%) had published patient-reported outcome data. LIMITATIONS: Data
      were limited to self-reported descriptions of trials listed on the
      ClinicalTrial.gov database, which is the best compendium of trial information
      available, but it is neither a complete nor a fully accurate record of all
      trials. CONCLUSIONS: Patient-reported outcome use and reporting in breast cancer
      drug trials has remained relatively low despite calls for more patient-centered
      research. Increasing the collection and availability of patient-reported outcome
      data to guide clinical decisions will require aligned support from trial
      sponsors, researchers, journal editors, regulators and patient advocacy groups,
      who can all play important roles in implementing change.

PMID- 23539109
TI  - Challenges in the research ethics review of cluster randomized trials:
      international survey of investigators.
AB  - BACKGROUND: Cluster randomized trials (CRTs) complicate the interpretation of
      standard research ethics guidelines for several reasons. For one, the units of
      allocation, intervention, and observation often may differ within a single trial.
      In the absence of tailored and internationally accepted ethics guidelines for
      CRTs, researchers and research ethics committees have no common standard by which
      to judge ethically appropriate practices in CRTs. Moreover, lack of familiarity
      with and consideration of the unique features of the CRT design by research
      ethics committees may cause difficulties in the research ethics review process,
      and amplify problems such as variability in the requirements and decisions
      reached by different research ethics committees. PURPOSE: We aimed to
      characterize research ethics review of CRTs, examine investigator experiences
      with the ethics review process, and assess the need for ethics guidelines for
      CRTs. METHODS: An electronic search strategy implemented in MEDLINE was used to
      identify and randomly sample 300 CRTs published in English language journals from
      2000 to 2008. A web-based survey with closed- and open-ended questions was
      administered to corresponding authors in a series of six contacts. RESULTS: The
      survey response rate was 64%. Among 182 of 285 eligible respondents, 91%
      indicated that they had sought research ethics approval for the identified CRT,
      although only 70% respondents reported research ethics approval in the published
      article. Nearly one-third (31%) indicated that they have had to meet with ethics
      committees to explain aspects of their trials, nearly half (46%) experienced
      variability in the ethics review process in multijurisdictional trials, and 38%
      experienced negative impacts of the ethics review process on their trials,
      including delays in trial initiation (28%), increased costs (10%), compromised
      ability to recruit participants (16%), and compromised methodological quality
      (9%). Most respondents (74%; 95% confidence interval (CI): 67%-80%) agreed or
      strongly agreed that there is a need to develop ethics guidelines for CRTs, and
      (70%; 95% CI: 63%-77%) that ethics committees could be better informed about
      distinct ethical issues surrounding CRTs. LIMITATIONS: Thirty-six percent of
      authors did not respond to the survey. Due to the absence of comparable results
      from a representative sample of authors of individually randomized trials, it is
      unclear to what extent the reported challenges result from the CRT design.
      CONCLUSIONS: CRT investigators are experiencing challenges in the research ethics
      review of their trials, including excessive delays, variability in process and
      outcome, and imposed requirements that can have negative consequences for study
      conduct. Investigators identified a clear need for ethics guidelines for CRTs and
      education of research ethics committees about distinct ethical issues in CRTs.

PMID- 23539111
TI  - Reflections on Professor Jerome Cornfield's contributions to the US Food and Drug
      Administration.

PMID- 23539112
TI  - Reminiscences of Jerry Cornfield.

PMID- 23539110
TI  - IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for
      sickle cell painful episodes: rationale, design challenges, initial experience,
      and recommendations for future studies.
AB  - BACKGROUND: The hallmark of sickle cell disease (SCD) is pain from a vaso
      occlusive crisis. Although ambulatory pain accounts for most days in pain, pain
      is also the most common cause of hospitalization and is typically treated with
      parenteral opioids. The evidence base is lacking for most analgesic practice in
      SCD, particularly for the optimal opioid dosing for patient-controlled analgesia
      (PCA), in part because of the challenges of the trial design and conduct for this
      rare disease. PURPOSE: The purpose of this report is to describe our Network's
      experiences with protocol development, implementation, and analysis, including
      overall study design, the value of pain assessments rather than 'crisis'
      resolution as trial endpoints, and alternative statistical analysis strategies.
      METHODS: The Improving Pain Management and Outcomes with Various Strategies
      (IMPROVE) PCA trial was a multisite inpatient randomized controlled trial
      comparing two PCA-dosing strategies in adults and children with SCD and acute
      pain conducted by the SCD Clinical Research Network. The specified primary
      endpoint was a 25-mm change in a daily average pain intensity using a Visual
      Analogue Scale, and a number of related pain intensity and pain interference
      measures were selected as secondary efficacy outcomes. A time-to-event analysis
      strategy was planned for the primary endpoint. RESULTS: Of 1116 individuals
      admitted for pain at 31 participating sites over a 6-month period, 38 were
      randomized and 4 withdrawn. The trial was closed early due to poor accrual,
      reflecting a substantial number of challenges encountered during trial
      implementation. LIMITATIONS: While some of the design issues were unique to SCD
      or analgesic studies, many of the trial implementation challenges reflected the
      increasing complexity of conducting clinical trials in the inpatient setting with
      multiple care providers and evolving electronic medical record systems,
      particularly in the context of large urban academic medical centers. LESSONS
      LEARNED: Complicated clinical organization of many sites likely slowed study
      initiation. More extensive involvement of research staff and site principal
      investigator in the clinical care operations improved site performance. During
      the subsequent data analysis, alternative statistical approaches were considered,
      the results of which should inform future efficacy assessments and increase
      future trial recruitment success by allowing substantial reductions in target
      sample size. CONCLUSIONS: A complex randomized analgesic trial was initiated
      within a multisite disease network seeking to provide an evidence base for
      clinical care. A number of design considerations were shown to be feasible in
      this setting, and several pain intensity and pain interference measures were
      shown to be sensitive to time- and treatment-related improvements. While the
      premature closure and small sample size precluded definitive conclusions
      regarding treatment efficacy, this trial furnishes a template for design and
      implementation considerations that should improve future SCD analgesic trials.

PMID- 23539113
TI  - Clinician-trialist rounds: 15. Ways to advance your career by saying 'no'--part
      3: how to say 'no', nicely.

PMID- 23539114
TI  - From ClinicalTrials.gov trial registry to an analysis-ready database of clinical
      trial results.
AB  - BACKGROUND: The ClinicalTrials.gov web site provides a convenient interface to
      look up study results, but it does not allow downloading data in a format that
      can be readily used for quantitative analyses. PURPOSE: To develop a system that
      automatically downloads study results from ClinicalTrials.gov and provides an
      interface to retrieve study results in a spreadsheet format ready for analysis.
      METHODS: Sherlock((r)) identifies studies by intervention, population, or outcome
      of interest and in seconds creates an analytic database of study results ready
      for analyses. The outcome classification algorithms used in Sherlock were
      validated against a classification by an expert. CONCLUSIONS: Having a database
      ready for analysis that can be updated automatically, dramatically extends the
      utility of the ClinicalTrials.gov trial registry. It increases the speed of
      comparative research, reduces the need for manual extraction of data, and permits
      answering a vast array of questions.

PMID- 23539115
TI  - Atherosclerosis in the Renaissance elite: Ferdinand I King of Naples (1431-1494).

PMID- 23539116
TI  - Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet
      autoantibody-positive children.
AB  - AIMS/HYPOTHESIS: Islet autoantibody-positive children progress to type 1 diabetes
      at variable rates. In our study, we asked whether characteristic autoantibody
      and/or gene profiles could be defined for phenotypes showing extreme progression.
      METHODS: Autoantibodies to insulin (IAA), GAD (GADA), insulinoma-associated
      antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) were measured in follow-up sera,
      and genotyping for type 1 diabetes susceptibility genes (HLA-DR/HLA-DQ, INS
      variable number of tandem repeats [VNTR] and single nucleotide polymorphisms at
      PTPN22, PTPN2, ERBB3, IL2, SH2B3, CTLA4, IFIH1, KIAA0350 [also known as CLEC16A],
      CD25, IL18RAP, IL10, COBL) was performed on the DNA samples of children born to a
      parent with type 1 diabetes and prospectively followed from birth for up to 22
      years. RESULTS: Of the 1,650 children followed, 23 developed multiple
      autoantibodies and progressed to diabetes within 3 years (rapid progressors),
      while 24 children developed multiple autoantibodies and remained non-diabetic for
      more than 10 years from seroconversion (slow progressors). Rapid and slow
      progressors were similar with respect to HLA-DR/HLA-DQ genotypes, development of
      IAA, GADA and ZnT8A, and progression to multiple autoantibodies. In contrast, IA
      2A development was considerably delayed in the slow progressors. Furthermore,
      both groups were effectively distinguished by the combined presence or absence of
      type 1 diabetes susceptibility alleles of non-HLA genes, most notably IL2, CD25,
      INS VNTR, IL18RAP, IL10, IFIH1 and PTPN22, and discrimination was improved among
      children carrying high-risk HLA-DR/HLA-DQ genotypes. CONCLUSIONS/INTERPRETATION:
      Our data suggest that genotypes of non-HLA type 1 diabetes susceptibility genes
      influence the likelihood or rate of diabetes progression among children with
      multiple islet autoantibodies.

PMID- 23539117
TI  - Multitasking on the run.
AB  - Researchers combine genetics and imaging to reveal that individual granule cells
      in the cerebellum integrate sensory and motor information.

PMID- 23539119
TI  - Repair of lipopolysaccharide-induced acute lung injury in mice by endothelial
      progenitor cells, alone and in combination with simvastatin.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are involved in endothelium
      repair of acute lung injury (ALI). Numerous studies have demonstrated that
      statins can promote EPC function in vitro and in vivo; therefore, the purpose of
      this study was to determine whether simvastatin enhances the function of EPCs
      participating in the repair of ALI. METHODS: BALB/C mice were initially
      pretreated with simvastatin by intraperitoneal administration 24 h before, and
      again at the time of, intratracheal instillation of lipopolysaccharide (LPS) and
      subsequently treated with EPCs by i.v. transplantation 2 h later. The effects of
      capillary permeability, endothelium repair, and inflammatory cytokines were
      measured. RESULTS: This study revealed that both simvastatin administration and
      EPC transplantation can reduce the severity of LPS-induced ALI in mice, and the
      effect can be further improved by combining the two therapies. CONCLUSIONS: The
      administration of simvastatin and EPC transplantation can reduce the severity of
      LPS-induced ALI in mice, and improvement is moderately enhanced in some respects
      when EPC transplantation is combined with simvastatin administration. The
      beneficial role of simvastatin on EPCs may be a component of its pleiotropic
      effects. Although the exact mechanism remains unknown, the combined
      administration of simvastatin and EPC transplantation may be a potentially
      important, cell-based, inflammation-mediated therapy for patients with ALI/ARDS.

PMID- 23539118
TI  - Combination of 15N reverse labeling and afterglow spectroscopy for assigning
      membrane protein spectra by magic-angle-spinning solid-state NMR: application to
      the multidrug resistance protein EmrE.
AB  - Magic-angle-spinning (MAS) solid-state NMR spectroscopy has emerged as a viable
      method to characterize membrane protein structure and dynamics. Nevertheless, the
      spectral resolution for uniformly labeled samples is often compromised by
      redundancy of the primary sequence and the presence of helical secondary
      structure that results in substantial resonance overlap. The ability to simplify
      the spectrum in order to obtain unambiguous site-specific assignments is a major
      bottleneck for structure determination. To address this problem, we used a
      combination of (15)N reverse labeling, afterglow spectroscopic techniques, and
      frequency-selective dephasing experiments that dramatically improved the ability
      to resolve peaks in crowded spectra. This was demonstrated using the polytopic
      membrane protein EmrE, an efflux pump involved in multidrug resistance. Residues
      preceding the (15)N reverse labeled amino acid were imaged using a 3D NCOCX
      afterglow experiment and those following were recorded using a frequency
      selective dephasing experiment. Our approach reduced the spectral congestion and
      provided a sensitive way to obtain chemical shift assignments for a membrane
      protein where no high-resolution structure is available. This MAS methodology is
      widely applicable to the study of other polytopic membrane proteins in functional
      lipid bilayer environments.

PMID- 23539120
TI  - Linking hematological, biochemical, genotoxic, and behavioral responses to crude
      oil in the Amazon fish Colossoma macropomum (Cuvier, 1816).
AB  - Despite safety protocols, crude oil extraction and transportation in the Amazon
      basin has a potential for inadvertent oil spills, which can impact aquatic
      organisms in local rivers. The objective of this study was to assess the effects
      of crude oil on juvenile Amazonian fish tambaqui, Colossoma macropomum, at
      various biological levels. Furthermore, the effect of crude oil on response to
      alarm substance, an important communication system in fish, was reported for the
      first time. Fish exposed to crude oil showed a 90 % decrease in their response to
      alarm substance and a 60 % decrease in swimming activity relative to control
      fish. Basic hematology was not affected, although an increase of 200 % of DNA
      damage and an increase of GST activity were observed in animals exposed to crude
      oil. Inverse correlations were found between genotoxicity end points and
      behavioral parameters, suggesting that genotoxic end points can also reflect
      behavioral changes.

PMID- 23539122
TI  - Submuscular bridge plating for complex pediatric femur fractures is reliable.
AB  - BACKGROUND: Complex, high-energy pediatric femur diaphyseal fractures cannot be
      treated reliably by conventional methods: casting is not suitable for polytrauma
      and large children, external fixation is associated with a high rate of
      malalignment and refractures, elastic nails are unsuitable for unstable fractures
      and metaphyseal areas, and lateral trochanteric entry rigid nails cannot address
      proximal and distal fragments and need relatively large medullary canals. A few
      centers have reported that submuscular bridge plating (SBP) is associated with
      minimal complications, but these findings require confirmation.
      QUESTIONS/PURPOSES: We asked whether SBP (1) reproducibly leads to union in
      unstable fractures with a low complication rate, (2) leads to reasonable
      alignment and leg length equality (3), is unaffected by age, weight, or location
      of fracture, and (4) is associated with no or minimal refracture after hardware
      removal. METHODS: We retrospectively reviewed 60 fractures in 58 patients with
      pediatric diaphyseal femoral fractures treated with SBP from 1999 to 2011. The
      average age was 9 years. Forty (67%) of the fractures were unstable. Minimum
      followup was 2.4 months (average, 15.5 months; range, 2.4-50.6 months). RESULTS:
      All fractures healed well and all patients returned to full activity. Two of the
      58 patients (3%) had major complications leading to unplanned surgeries: one
      implant failure and one deep infection in an old open fracture. None of the
      patients developed clinically important malalignment or leg length discrepancy.
      Implant removal was performed in 49 patients without complications. CONCLUSIONS:
      SBP provided reliable fixation and healing for complex pediatric femur fractures
      and can have a broader application in the orthopaedic community. SBP is our
      preferred method for unstable fractures or fractures of the proximal and distal
      shaft.

PMID- 23539121
TI  - Expression of CD163 prevents apoptosis through the production of granulocyte
      colony-stimulating factor in meningioma.
AB  - BACKGROUND: CD163 is a 130-kDa transmembrane protein expressed in human monocytes
      and macrophages, and the aberrant expression of CD163 in breast and colorectal
      cancer associated with patients' poor prognosis was reported. Here, we analyzed
      the expression of CD163 in meningioma, a common intracranial tumor, and its
      molecular mechanism in association with meningioma progression. METHODS: First,
      we performed immunohistochemical analysis using 50 human meningioma specimens.
      Next, we established CD163-overexpressing human meningioma cell lines and
      investigated its roles in tumor progression in vitro and in vivo. RESULTS:
      Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive
      for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%)
      cases. Furthermore, CD163 expression was correlated with histological atypical
      parameters that directly predict the prognosis of meningioma. CD163
      overexpressing meningioma cells showed significant suppression of apoptosis and
      accelerated tumor growth in nude mice. In addition, unexpected splenomegaly
      affiliated with the xenograft predicted tumor-derived granulocyte colony
      stimulating factor (G-CSF) production, which was confirmed by reverse
      transcription polymerase chain reaction and enzyme-linked immunosorbent assay.
      CONCLUSIONS: To our knowledge, this is the first report that demonstrates CD163
      expression in meningioma not only by immunohistochemistry but also by reverse
      transcription polymerase chain reaction, using primary culture cells, and
      provides the novel molecular function of CD163 to prevent apoptosis through the
      production of G-CSF in meningioma.

PMID- 23539123
TI  - Negative pressure wound therapy is associated with resolution of incisional
      drainage in most wounds after hip arthroplasty.
AB  - BACKGROUND: Persistent wound drainage after hip arthroplasty is a risk factor for
      periprosthetic infection. Negative pressure wound therapy (NPWT) has been used in
      other fields for wound management although it is unclear whether the technique is
      appropriate for total hip arthroplasty. QUESTIONS/PURPOSES: We determined (1) the
      rate of wound complications related to use of NPWT for persistent incisional
      drainage after hip arthroplasty; (2) the rate of resolution of incisional
      drainage using this modality; and (3) risk factors for failure of NPWT for this
      indication. METHODS: In a pilot study we identified 109 patients in whom NPWT was
      used after hip arthroplasty for treating postoperative incisional drainage
      between April 2006 and April 2010. On average, the NPWT was placed on
      postoperative Day 3 to 4 (range, 2-9 days) and applied for 2 days (range, 1-10
      days). We then determined predictors of subsequent surgery. Patients were
      followed until failure or a minimum of 1 year (average, 29 months; range, 1-62
      months). RESULTS: Eighty-three patients (76%) had no further surgery and 26
      patients (24%) had subsequent surgery: 11 had superficial irrigation and
      debridement (I&D), 12 had deep I&D with none requiring further surgery, and three
      ultimately had component removal. Predictors of subsequent surgery included
      international normalized ratio level greater than 2, greater than one prior hip
      surgery, and device application greater than 48 hours. There were no wound
      related complications associated with NPWT. CONCLUSIONS: The majority of our
      patients had cessation of wound drainage with NPWT. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 23539124
TI  - A review of current fixation use and registry outcomes in total hip arthroplasty:
      the uncemented paradox.
AB  - BACKGROUND: The majority (86%) of THAs performed in the United States are
      uncemented. This may increase the revision burden if uncemented fixation is
      associated with a higher risk of revision than other approaches.
      QUESTION/PURPOSES: We sought to investigate trends for use of uncemented fixation
      and to analyze age-stratified risk of revision comparing cemented, hybrid, and
      uncemented fixation as reported by national hip arthroplasty registries. METHODS:
      Data were extracted from the annual reports of seven national hip arthroplasty
      registries; we included all national registries for which annual reports were
      available in English or a Scandinavian language, if the registry had a history of
      more than 5 years of data collection. RESULTS: Current use of uncemented fixation
      in primary THAs varies between 15% in Sweden and 82% in Canada. From 2006 to 2010
      the registries of all countries reported overall increases in the use of
      uncemented fixation; Sweden reported the smallest absolute increase (from 10% to
      15%), and Denmark reported the greatest absolute increase (from 47% to 68%).
      Looking only at the oldest age groups, use of uncemented fixation also was
      increasing during the period. In the oldest age group of each of the registries
      we surveyed (age older than 65 years for England-Wales; age older than 75 years
      in three registries), cemented fixation was associated with a lower risk of
      revision than was uncemented fixation. CONCLUSIONS: Increasing use of uncemented
      fixation in THA is a worldwide phenomenon. This trend is paradoxic, given that
      registry data, which represent nationwide THA outcomes, suggest that cemented
      fixation in patients older than 75 years results in the lowest risk of revision.
      LEVEL OF EVIDENCE: Level II, systematic review. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 23539125
TI  - Is the bone-bonding ability of a cementless total hip prosthesis enhanced by
      alkaline and heat treatments?
AB  - BACKGROUND: Cementless total hip arthroplasty (THA) implants using alkaline and
      heat treatments were developed to enhance bone bonding. Although bone-bonding
      ability of the alkali- and heat-treated titanium surface has been demonstrated in
      animal studies, it remains unknown whether it enhances or provides durable bone
      bonding in humans. QUESTIONS/PURPOSES: We therefore (1) determined long-term
      survivorship, function, and radiographic signs of failure of fixation of alkali-
      and heat-treated THA implants; and (2) histologically examined their bone-bonding
      ability in two human retrievals. METHODS: We retrospectively reviewed 58 patients
      who underwent 70 primary THAs, of whom 67 were available for minimum followup of
      8 years (average, 10 years; range, 8-12 years). Survival rate was calculated. Hip
      function was evaluated using the Japan Orthopaedic Association (JOA) hip scores,
      and radiographic signs of implant failure were determined from anteroposterior
      radiographs. Two retrieved implants were investigated histologically. RESULTS:
      Using revision for any reason as the end point, the overall survival rate was 98%
      (95% confidence interval, 96%-100%) at 10 years. The patients' average JOA hip
      scores improved from 47 points preoperatively to 91 points at the time of the
      last followup. No implant had radiographic signs of loosening. Histologically we
      observed bone in the pores 2 weeks after implantation in one specimen and
      apparently direct bonding between bone and the titanium surface in its deep pores
      8 years after implantation. CONCLUSIONS: Cementless THA implants with alkaline
      and heat treatments showed a high survival rate. Further study is required to
      determine whether the treatment enhances direct bone bonding.

PMID- 23539126
TI  - Doctors' leaders urge government to amend commissioning regulations.

PMID- 23539127
TI  - Cachexia as a major public health problem: frequent, costly, and deadly.
AB  - Perception of healthy body size and composition differs considerably across the
      globe, ethnic groups, cultures, and even inside medical community. Although the
      concept of ideal body weight has evolved over the past decades, the observation
      that weight loss can have more deleterious effects within a short-term period
      than weight gain has remained rather consistent. Weight loss, as a prelude to
      cachexia, occurs frequently in a variety of disease states and meets the
      requirements of a global public health problem. Consequently, interventions to
      prevent and control chronic diseases require a comprehensive approach that
      targets a population as a whole and includes both prevention and treatment
      strategies. Around the globe, cachexia awareness campaigns and expanding the
      current public health priorities to highlight the cachexia magnitude and areas of
      interventions is necessary. Simultaneously, scientific efforts should provide us
      with more reliable estimates of body wasting and cachexia as well as
      pathophysiology of cachexia-associated death. As certain proportion of patients
      will, irrespective of preventive measures, eventually develop cachexia, a quest
      for effective remedy remains vital. 

PMID- 23539128
TI  - Temporal distribution and weather correlates of Norway rat (Rattus norvegicus)
      infestations in the city of Madrid, Spain.
AB  - Urban Norway rats are challenging pests, posing significant health and economic
      threats. Implementing ecologically based integrated rodent management (EBIRM)
      programmes relies primarily on the understanding of ecological relationships
      between rodents and their environments, with emphasis on the processes
      influencing rodent populations in the target ecosystem. We investigated the
      temporal distribution of urban Norway rat infestations in Madrid, Spain, and
      tested for the association of such infestations with temperature, relative
      humidity and precipitation by fitting a multivariate Poisson generalized linear
      model to a 3-year (2006-2008) daily time series of 4,689 Norway rat sightings.
      Norway rat infestations showed a marked seasonality, peaking in the summer. Most
      Norway rat sightings were reported on Mondays. Minimum temperature and relative
      humidity were positively associated with Norway rat infestation, whereas the
      association with precipitation was negative. The time series was adequately
      explained by the model. We identified previously unrecognized time periods that
      are more prone to Norway rat infestation than others and generated hypotheses
      about the association between weather, human outdoor activity, resource
      availability, rodent activity and population size. This provided local
      authorities engaged in preserving urban ecosystem health with basic research
      information to predict future rodent outbreaks and support the implementation of
      EBIRM programmes in urban areas.

PMID- 23539129
TI  - Experimental evidence for American bullfrog (Lithobates catesbeianus)
      susceptibility to chytrid fungus (Batrachochytrium dendrobatidis).
AB  - The emerging fungal pathogen, Batrachochytrium dendrobatidis (Bd), has been
      associated with global amphibian population declines and extinctions. American
      bullfrogs (Lithobates catesbeianus) are widely reported to be a tolerant host and
      a carrier of Bd that spreads the pathogen to less tolerant hosts. Here, we
      examined whether bullfrogs raised from eggs to metamorphosis in outdoor mesocosms
      were susceptible to Bd. We experimentally exposed metamorphic juveniles to Bd in
      the laboratory and compared mortality rates of pathogen-exposed animals to
      controls (non-exposed) in two separate experiments; one using a Bd strain
      isolated from a Western toad and another using a strain isolated from an American
      bullfrog. We wanted to examine whether metamorphic bullfrogs were susceptible to
      either of these strains. We show that bullfrogs were susceptible to one strain of
      Bd and not the other. In both experiments, infection load detected in the skin
      decreased over time, suggesting that metamorphic bullfrogs from some populations
      may be inefficient long-term carriers of Bd.

PMID- 23539130
TI  - Prognostic significance and therapeutic option of heart rate variability in
      chronic kidney disease.
AB  - Cardiovascular disease (CVD) begins early in the course of chronic kidney disease
      (CKD) and is the leading cause of death in patients with CKD. Preventing the
      development of CVD and establishing new clinical tools for identifying high-risk
      individuals, particularly those with an increased risk for cardiac death, is of
      clinical importance. Abnormality of heart rate variability (HRV) has been shown
      to be associated with CVD and CKD. Assessment of HRV is based on analysis of
      consecutive normal R-R intervals and may provide quantitative information on the
      modulation of cardiac vagal and sympathetic nerve input. In this brief
      manuscript, increased CVD risk among CKD patients, mechanisms due to autonomic
      nerves dysfunction, changes of HRV and potential measures to ameliorate clinical
      prognostic of CKD patients will be discussed. 

PMID- 23539131
TI  - The influence of ethnicity and gender on the association between measured obesity
      and cardiorespiratory fitness with self-rated overweight, physical activity and
      health.
AB  - BACKGROUND: Little is known about how ethnicity may influence how self-rated
      physical activity (PA) and obesity relates to measured obesity, cardiorespiratory
      fitness and self-rated health. AIMS: To examine the influence of ethnicity on the
      association between: (1) self-rated and measured obesity; (2) self-reported PA
      and cardiorespiratory fitness; and (3) obesity and PA with self-rated health.
      METHODS: Data from NHANES 1999-2004 (2,981 adults) was used. RESULTS: Compared to
      white and overweight black men, Hispanic men were less likely to consider
      themselves overweight (OR = 0.36-0.56). Compared to white men, black active men
      were more likely to report being more active than their peers (OR = 1.44) but
      were less likely to be fit (OR = 0.74). Black active women and non-white
      overweight women were less likely to self-rate as having very good or excellent
      health as compared to white women with similar self-reported and measured health
      factors. CONCLUSIONS: Ethnicity and gender influence how self-rated and measured
      health factors interrelate.

PMID- 23539132
TI  - An evaluation of the condom distribution scheme (C-Card) with young people in
      Northeast England.
AB  - AIMS: To evaluate a local C-Card scheme from the perspectives of young people in
      order to determine how well it had worked in improving access to condoms and in
      providing young people with appropriate information to make healthier choices
      around safer sex. METHODS: Secondary analysis of a year's worth of existing
      registration and monitoring data routinely collected by the C-Card scheme, two
      focus group discussions with 14 young people (eight males and six females) and a
      short questionnaire-based survey of 55 young people. RESULTS: The evidence
      suggested that the C-Card scheme is an effective tool for ensuring that young
      people know how to use a condom correctly. Ease of access and increased knowledge
      were key issues of effectiveness to emerge from the findings. The scheme also
      served as a mechanism for young people to be referred on to other sexual health
      services and the data appear to indicate that this was something that was taken
      up by young people. CONCLUSIONS: The young people who used C-Card generally
      viewed the scheme as an effective mechanism in terms of accessing condoms and the
      number of outlets available for acquiring condoms. In order for C-Card to become
      successful with young people, advertising needs to be improved to increase their
      awareness of the scheme.

PMID- 23539133
TI  - Cellular distribution of the NMDA-receptor activated synapto-nuclear messenger
      Jacob in the rat brain.
AB  - In previous work, we found that the protein messenger Jacob is involved in N
      methyl-D-aspartate receptor (NMDAR) signaling to the nucleus and cAMP response
      element-binding protein (CREB) mediated gene expression in hippocampal primary
      neurons. Particularly, extrasynaptic NMDAR activation drives Jacob efficiently
      into the nucleus where it then induces gene expression that promotes
      neurodegeneration. However, the protein also translocates to the nucleus in CA1
      neurons after Schaffer collateral long-term potentiation (LTP) but not long-term
      depression (LTD), suggesting that Jacob might be involved in hippocampal and LTP
      dependent learning and memory processes. Not much is known about the cellular and
      subcellular distribution of the protein in brain. In this paper, we provide an
      overview of the expression of Jacob in rat brain with special emphasis on the
      hippocampus. We show that Jacob is abundant in hippocampal pyramidal neurons and
      interneurons but absent from astrocytes and microglia. Interestingly, we found
      that Jacob is also present in mossy fiber axons. Double immunofluorescence
      confocal laser scans with presynaptic markers demonstrate that Jacob is indeed
      found at excitatory but not inhibitory presynaptic sites. Accordingly, we found
      no substantial co-localization of Jacob with a postsynaptic marker of inhibitory
      synapses, gephyrin. In contrast, almost all postsynaptic density protein 95 (PSD
      95) positive excitatory postsynaptic sites also exhibited strong Jacob
      immunofluorescence. Taken together, these data support a synaptic and nuclear
      role of Jacob that implicates long-distance NMDAR signaling to the nucleus in
      excitatory neurons. 

PMID- 23539134
TI  - Artemisinin-based combination therapy: knowledge and perceptions of patent
      medicine dealers in Owerri Metropolis, Imo State, Nigeria and implications for
      compliance with current malaria treatment protocol.
AB  - This study was done to access the knowledge and perceptions of Patent Medicine
      Dealers (PMDs) in Owerri Metropolis of Nigeria about Artemisinin Based
      Combination Therapy as first line treatment for malaria using structured pre
      tested questionnaires administered to 80 randomly selected and consenting
      respondents. About 67.5 and 32.5 % of males and females respectively participated
      in the study. Most of them (56.3 %) had secondary school education with about 50
      % having 5-10 years experience in the business. The level of knowledge was shown
      to be high (82.5 %), with 81.3 % having proper understanding of the term
      "artemisinin-based combination therapies (ACTs)" and 80 % knowing the correct
      dosage for ACTs. But despite the level of awareness, only 32.5 % knew the correct
      timing for administration of the drugs. The result of this study showed no
      significant relationship between the level of knowledge and either educational
      attainment (chi(2) = 4.889, df = 4, p value = 0.558) or the years of experience
      (chi(2) = 29.095, df = 4, p value = 0.000) although knowledge improved a bit as
      experience increased. 93.8 % in the study reported that ACTs are more effective
      than other anti-malarial drugs. The quantity of ACT available on counters are low
      and there is no significant relationship (chi(2) = 18.833, df = 6, p value =
      0.004) between the availability of ACT and the quantity of ACT available in stock
      at the time of this study. This study shows that awareness on ACTs has improved
      among PMDs, even though other anti-malarial drugs are still in use and are
      marketed by them. It becomes necessary that efforts towards awareness be scaled
      up with emphasis on recommended time of administration and correct prescriptions
      to enhance and sustain intermittent presumptive treatment as an effective method
      of malaria control since this group of people still provide the major access to
      drugs in Nigeria and other tropical endemic areas. 

PMID- 23539135
TI  - Black women's awareness of breast cancer disparity and perceptions of the causes
      of disparity.
AB  - Black women face the greatest breast cancer mortality burden of any racial or
      ethnic group in the United States. Breast cancer disparity is particularly
      pronounced in Chicago, where Black women were 62 percent more likely to die of
      breast cancer than their White counterparts in 2007. No work to date has examined
      views of disparity among a population living in the context of a large, well
      documented, and grave health disparity. We examined (1) awareness of breast
      cancer disparities among Black women in Chicago; and (2) Black women's
      perceptions of the causes of breast cancer disparity. Four focus groups with
      Black women were held in Chicago. Participants completed a brief survey about
      their views of breast cancer prior to the group discussion. In response to the
      survey question, "In your opinion, who is more likely to die from breast cancer?"
      51 % of participants believed all women have the same chance of dying from breast
      cancer. In focus group discussions, participants placed responsibility for
      disparity on individual behaviors and community culture. Participants believed
      that disparity resulted from Black women's lack of awareness of cancer screening
      and their failure to be screened or treated for breast cancer. The majority of
      participants were unaware of breast cancer mortality disparities. Moreover, while
      health researchers and professionals believe disparity in Chicago results from
      healthcare system inequalities, Black women largely viewed breast cancer
      disparity as a consequence of individual behaviors, knowledge and attitudes. 

PMID- 23539136
TI  - Medication-taking beliefs and diabetes in American Samoa: a qualitative inquiry.
AB  - In American Samoa (AS), nearly 22% of adults have type 2 diabetes. Diabetes is
      best managed by diet and lifestyle modifications and strict medication adherence.
      Cultural aspects might affect medication-taking beliefs, and thereby influence
      medication adherence. This study aims to explore diabetes medication-taking
      experiences and knowledge and related cultural beliefs in AS adults with diabetes
      and healthcare providers. Six focus groups were conducted with 39 AS adults with
      diabetes and individual interviews were performed with 13 diabetes healthcare
      providers. Data were transcribed and analyzed using NVivo 8 software. Themes
      pertaining to medication taking and adherence were identified. Patients and
      providers reported that barriers such as confusion about medications and concern
      about medication costs negatively influence medication taking, while cultural
      values and obligations both positively and negatively impact medication
      adherence. These findings help elucidate the relationship between medication
      taking beliefs and culture in AS adults with diabetes and highlight the
      importance of continued research within this population.

PMID- 23539137
TI  - Complex expression dynamics and robustness in C. elegans insulin networks.
AB  - Gene families expand by gene duplication, and resulting paralogs diverge through
      mutation. Functional diversification can include neofunctionalization as well as
      subfunctionalization of ancestral functions. In addition, redundancy in which
      multiple genes fulfill overlapping functions is often maintained. Here, we use
      the family of 40 Caenorhabditis elegans insulins to gain insight into the balance
      between specificity and redundancy. The insulin/insulin-like growth factor (IIS)
      pathway comprises a single receptor, DAF-2. To date, no single insulin-like
      peptide recapitulates all DAF-2-associated phenotypes, likely due to redundancy
      between insulin-like genes. To provide a first-level annotation of potential
      patterns of redundancy, we comprehensively delineate the spatiotemporal and
      conditional expression of all 40 insulins in living animals. We observe extensive
      dynamics in expression that can explain the lack of simple patterns of pairwise
      redundancy. We propose a model in which gene families evolve to attain
      differential alliances in different tissues and in response to a range of
      environmental stresses.

PMID- 23539138
TI  - Gene expression drives local adaptation in humans.
AB  - The molecular basis of adaptation--and, in particular, the relative roles of
      protein-coding versus gene expression changes--has long been the subject of
      speculation and debate. Recently, the genotyping of diverse human populations has
      led to the identification of many putative "local adaptations" that differ
      between populations. Here I show that these local adaptations are over 10-fold
      more likely to affect gene expression than amino acid sequence. In addition, a
      novel framework for identifying polygenic local adaptations detects recent
      positive selection on the expression levels of genes involved in UV radiation
      response, immune cell proliferation, and diabetes-related pathways. These results
      provide the first examples of polygenic gene expression adaptation in humans, as
      well as the first genome-scale support for the hypothesis that changes in gene
      expression have driven human adaptation.

PMID- 23539139
TI  - HCFC1 is a common component of active human CpG-island promoters and coincides
      with ZNF143, THAP11, YY1, and GABP transcription factor occupancy.
AB  - In human transcriptional regulation, DNA-sequence-specific factors can associate
      with intermediaries that orchestrate interactions with a diverse set of chromatin
      modifying enzymes. One such intermediary is HCFC1 (also known as HCF-1). HCFC1,
      first identified in herpes simplex virus transcription, has a poorly defined role
      in cellular transcriptional regulation. We show here that, in HeLa cells, HCFC1
      is observed bound to 5400 generally active CpG-island promoters. Examination of
      the DNA sequences underlying the HCFC1-binding sites revealed three sequence
      motifs associated with the binding of (1) ZNF143 and THAP11 (also known as
      Ronin), (2) GABP, and (3) YY1 sequence-specific transcription factors. Subsequent
      analysis revealed colocalization of HCFC1 with these four transcription factors
      at ~90% of the 5400 HCFC1-bound promoters. These studies suggest that a
      relatively small number of transcription factors play a major role in HeLa-cell
      transcriptional regulation in association with HCFC1.

PMID- 23539140
TI  - Measurement Issues: Screening and diagnostic instruments for autism spectrum
      disorders - lessons from research and practice.
AB  - BACKGROUND AND SCOPE: Significant progress has been made over the past two
      decades in the development of screening and diagnostic instruments for autism
      spectrum disorders (ASD). This article reviews this progress, including recent
      innovations, focussing on those instruments for which the strongest research data
      on validity exists, and then turns to addressing issues arising from their use in
      clinical settings. FINDINGS: Research studies have evaluated the ability of
      screens to prospectively identify cases of ASD in population-based and clinically
      referred samples, as well as the accuracy of diagnostic instruments to map onto
      'gold standard' clinical best estimate diagnosis. However, extension of the
      findings to clinical services must be done with caution, with a full
      understanding that instrument properties are sample-specific. Furthermore, we are
      limited by the lack of a true test for ASD, which remains a behaviourally-defined
      disorder. In addition screening and diagnostic instruments help clinicians least
      in the cases where they are most in want of direction, since their accuracy will
      always be lower for marginal cases. CONCLUSION: Instruments help clinicians to
      collect detailed, structured information and increase accuracy and reliability of
      referral for in-depth assessment and recommendations for support, but further
      research is needed to refine their effective use in clinical settings.

PMID- 23539142
TI  - A microfluidic platform for electrical detection of DNA hybridization.
AB  - Current methods used for detection of DNA hybridization involve the use of DNA
      microarrays which require overnight incubation times along with bulky and
      expensive fluorescent scanners. Here, we demonstrate electrical detection of DNA
      hybridization in an oligonucleotide functionalized microfluidic channel. We use
      microchannels functionalized with DNA probes integrated with electrodes for
      measuring conductance across the channel. As beads conjugated with the target DNA
      passing through the channel are captured on the surface, we are able to
      electrically detect changes in resistance due to bead capture. Our assay can be
      completed in less than an hour using less than a microliter of reagent, and has
      the potential for extensive multiplexing. Such a device can be useful as a
      handheld platform in a clinical setting where one would need to rapidly genotype
      a small number of genes rapidly.

PMID- 23539141
TI  - Development of animal models underlining mechanistic connections between prostate
      inflammation and cancer.
AB  - The characterization of animal models has indicated that the genetic, dietary and
      environmental factors and hormonal imbalance may influence the risk to develop
      prostate inflammatory lesions and prostate cancer (PC) confirming human
      epidemiologic data. It is now established that the prostate inflammatory response
      typically results in major changes in the local microenvironment of epithelial
      cells of the prostate gland, including an intense stromal remodeling, activation
      of fibroblasts, infiltration of immune cells such as mast cells, macrophages and
      B and T lymphocytes and collagen deposition. The immune cells recruited at
      prostate inflammatory lesions and myofibroblasts may contribute to the release of
      numerous pro-inflammatory cytokines and chemokines that in turn can promote the
      oxidative stress, genomic instability and proliferation of epithelial cells. The
      accumulation of additional genetic and/or epigenetic alterations in prostatic
      stem/progenitor cells may subsequently culminate to their malignant
      transformation and PC initiation and progression and more particularly with
      advancing age. The potential mechanistic relationships between the molecular
      events associated with the persistent inflammatory response and prostate
      carcinogenesis have important implications for optimizing the current therapies
      against different prostatic disorders and PCs.

PMID- 23539144
TI  - Size and anatomic location of ruptured intracranial aneurysms in patients with
      single and multiple aneurysms: a retrospective study from a single center.
AB  - BACKGROUND AND PURPOSE: The difference in the relationship between the size of
      intracranial aneurysms (IAs) and their risk of rupture in patients with singe IAs
      versus those with multiple IAs is unclear. We sought to retrospectively analyze
      the size of ruptured IAs (RIAs) in patients with single and multiple IAs in order
      to study this relationship further. METHODS: We retrospectively measured the size
      and location of RIAs in all patients who presented to our institute with an acute
      subarachnoid hemorrhage between 1 January 2005 and 31 December 2010. The IAs were
      classified by size into very small IAs or VSAs (<=3 mm), small IAs or SAs (>3 mm
      but <=7 mm) and others (>7 mm). RESULTS: 379 patients (281 with a single IA,
      Group 1 and 98 with multiple IAs, Group 2) with 419 treated RIAs were included in
      the study. VSAs and SAs constituted the majority of RIAs in both groups (33.5%
      and 45.2% in Group 1 and 24.6% and 50.7% in Group 2) and the mean size of the
      RIAs was not different between the two groups. VSAs constituted almost two-thirds
      of all RIAs in certain locations whereas IAs > 7 mm in size did not constitute
      more than a third of the RIAs at any of the arterial locations. CONCLUSIONS: The
      high incidence of VSAs, particularly in certain locations in both patient
      subgroups, suggests that current diagnostic, prognostic and therapeutic options
      in the management of IAs should be more tailored towards the management of these
      difficult-to-treat lesions.

PMID- 23539143
TI  - Delay in the administration of appropriate antimicrobial therapy in
      Staphylococcus aureus bloodstream infection: a prospective multicenter hospital
      based cohort study.
AB  - OBJECTIVES: Early broad-spectrum antimicrobial treatment reduces mortality in
      patients with septic shock. In a multicenter, prospective observational study, we
      explored whether delayed appropriate antimicrobial therapy (AAT) influences
      outcome in Staphylococcus aureus bloodstream infection (SAB). METHODS: Two
      hundred and fifty-six patients with SAB from ten German study centers were
      enrolled and followed for 3 months. Predisposing factors, clinical features,
      diagnostic procedures, antimicrobial therapy, and outcome were recorded. The
      appropriateness of antimicrobial therapy was judged by a trained physician based
      on in vitro activity, dosage, and duration of therapy. Therapy was considered to
      be delayed when more than 24 h elapsed between the first positive blood culture
      and the start of appropriate therapy. The association of delayed therapy with
      overall mortality and SAB-related events (i.e., attributable mortality or late
      SAB-related complications) was assessed by crosstabulation and propensity score
      based logistic regression. RESULTS: One hundred and sixty-eight patients received
      AAT during their hospital stay, of whom 42 (25%) received delayed AAT. The
      overall mortality and the occurrence of severe sepsis or septic shock were lower
      in patients with delayed AAT, pointing towards confounding by indication.
      Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval
      [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95% CI [0.47
      4.51], p 0.52) also failed to show a significant impact of delayed AAT on
      outcome. CONCLUSION: In patients with SAB, early AAT may not improve survival.
      However, confounding by indication is a major challenge when analyzing and
      interpreting observational studies on the impact of delayed AAT.

PMID- 23539146
TI  - Applying electrical impedance tomography to dynamically monitor retroperitoneal
      bleeding in a renal trauma patient.

PMID- 23539145
TI  - A new instrument to assess physician skill at thoracic ultrasound, including
      pleural effusion markup.
AB  - BACKGROUND: To reduce complications and increase success, thoracic ultrasound is
      recommended to guide all chest drainage procedures. Despite this, no tools
      currently exist to assess proceduralist training or competence. This study aims
      to validate an instrument to assess physician skill at performing thoracic
      ultrasound, including effusion markup, and examine its validity. METHODS: We
      developed an 11-domain, 100-point assessment sheet in line with British Thoracic
      Society guidelines: the Ultrasound-Guided Thoracentesis Skills and Tasks
      Assessment Test (UGSTAT). The test was used to assess 22 participants (eight
      novices, seven intermediates, seven advanced) on two occasions while performing
      thoracic ultrasound on a pleural effusion phantom. Each test was scored by two
      blinded expert examiners. Validity was examined by assessing the ability of the
      test to stratify participants according to expected skill level (analysis of
      variance) and demonstrating test-retest and intertester reproducibility by
      comparison of repeated scores (mean difference [95% CI] and paired t test) and
      the intraclass correlation coefficient. RESULTS: Mean scores for the novice,
      intermediate, and advanced groups were 49.3, 73.0, and 91.5 respectively, which
      were all significantly different (P < .0001). There were no significant
      differences between repeated scores. CONCLUSIONS: Procedural training on
      mannequins prior to unsupervised performance on patients is rapidly becoming the
      standard in medical education. This study has validated the UGSTAT, which can now
      be used to determine the adequacy of thoracic ultrasound training prior to
      clinical practice. It is likely that its role could be extended to live patients,
      providing a way to document ongoing procedural competence.

PMID- 23539147
TI  - The relationship between serum calcium level, blood lipids, and blood pressure in
      hypertensive and normotensive subjects who come from a normal university in east
      of China.
AB  - Previous studies revealed that low calcium intake is related to high prevalence
      of cardiovascular diseases such as hypertension. However, the relationship
      between serum calcium and blood pressure was unclear. The prevalence of
      hypertension is high in China. Thus, the aim of this study was to evaluate the
      serum calcium level between hypertensive and normotensive groups and to
      investigate the correlation between serum calcium, blood pressure, and blood
      lipid parameters. A total of 1,135 adult subjects participated in this study and
      were divide into two study groups: a hypertensive group (n = 316) who had 140
      mmHg or higher in systolic blood pressure (SBP) or 90 mmHg or higher in diastolic
      blood pressure (DBP) and an age- and sex-matched normotensive group (n = 819, 120
      mmHg or less SBP and 80 mmHg or less DBP). Our results indicate a significant
      trend for men (60 years old or older) in the direction of decreasing blood
      pressure with increasing serum calcium level, but no trend for women was
      indicated. In the normotensive group, a significant positive correlation was
      found between DBP and total cholesterol (P < 0.01) and triglyceride (P < 0.01),
      Likewise, triglyceride was positively correlated with SBP (P < 0.01). Overall,
      these data suggest that serum calcium may have an influence in the blood pressure
      of older male subjects with hypertension and in blood lipid profiles of
      normotensive subjects.

PMID- 23539148
TI  - Paraphyseal changes on bone-age studies predict risk of delayed radiation
      associated skeletal complications following total body irradiation.
AB  - BACKGROUND: Children undergoing total body irradiation (TBI) often develop
      delayed skeletal complications. Bone-age studies in these children often reveal
      subtle paraphyseal changes including physeal widening, metaphyseal irregularity
      and paraphyseal exostoses. OBJECTIVE: To investigate whether paraphyseal changes
      on a bone-age study following TBI indicate a predisposition toward developing
      other radiation-associated skeletal complications. MATERIALS AND METHODS: We
      retrospectively reviewed medical records and bone-age studies of 77 children
      receiving TBI at our institution between 1995 and 2008 who had at least 2 years
      of clinical follow-up and one bone-age study after TBI. We graded bone-age
      studies according to the severity of paraphyseal changes. All documented skeletal
      complications following TBI were tabulated. Kendall's tau-b was used to examine
      associations between degree of paraphyseal change and development of a skeletal
      complication. RESULTS: Kendall's tau analyses showed that physeal widening and
      metaphyseal irregularity/sclerosis (tau = 0.87, P < 0.001) and paraphyseal
      exostoses (tau = 0.68, P < 0.001) seen on bone-age studies were significantly
      positively associated with the development of delayed skeletal complications
      following TBI. Thirty percent of children with no or mild paraphyseal changes
      developed a delayed skeletal complication, compared with 58% of children with
      moderate paraphyseal changes and 90% of children with severe paraphyseal changes.
      CONCLUSION: Paraphyseal changes identified on a bone-age study correlate
      positively with the development of delayed skeletal complications elsewhere in
      the skeleton following TBI.

PMID- 23539150
TI  - Bacillus subtilis SC02 supplementation causes alterations of the microbial
      diversity in grass carp water.
AB  - This study was conducted to evaluate the effects of Bacillus subtilis SC02
      supplement on water quality, microbial community diversity and structure in a
      grass carp (Ctenopharyngodon idellus) culture. Our selected strain, B. subtilis
      SC02, significantly reduced ammonia, nitrite and total nitrogen levels in water
      over an extended period compared with the control group. Pyrosequencing showed
      that the Shannon diversity index (Shannon) and species richness estimators (Chao)
      of the treatment group were higher, indicating that bacterial richness was
      significantly increased in the treatment group. The phyla Proteobacteria,
      Bacteroidetes and Actinobacteria were dominant in the treatment groups,
      accounting for 45, 21.9 and 21.9 % of the sequence reads, respectively. However,
      in sharp contrast, the control fishes were predominantly occupied by
      Proteobacteria (82.1 %) and Firmicutes (8.4 %). At the genus level, the microbial
      communities were different between the control and treatment groups, although the
      two groups shared similar genera. Additionally, some genera (such as Tepidimonas,
      Variovorax, Roseomonas, Rubritepida, Nitrobacter, etc.) only appeared in the
      treatment group, and many other genera only existed in the control group.
      Therefore, we conclude that the addition of the SC02 strain in water improves
      water quality, which may ultimately be a result of changes in microbial community
      diversity in grass carp cultures. 

PMID- 23539151
TI  - Anti-biofouling property of vanillin on Aeromonas hydrophila initial biofilm on
      various membrane surfaces.
AB  - Biofouling is a serious problem on filter membranes of water purification systems
      due to formation of bacterial biofilms, which can be detrimental to the membrane
      performance. Biofouling occurs on membrane surface and therefore greatly
      influences the physical and chemical aspects of the surface. Several membranes
      including microfiltration, ultrafiltration, and reverse osmosis (RO) membranes
      were used to learn about the anti-biofouling properties of vanillin affecting the
      membrane performances. Vanillin has been recognized as a potential quorum
      quenching compound for Aeromonas hydrophila biofilms. The initial attachment and
      dynamics of biofilm growth were monitored using scanning electron microscopy and
      confocal laser scanning microscopy. Biofilm quantities were measured using a
      plate count method and total protein determinations. Vanillin addition was
      effective in the prevention of biofilm formation on the tested membrane surfaces.
      Among the membranes, RO membranes made with cellulose acetate showed the most
      substantial reduction of biofilm formation by addition of vanillin. The biofilm
      reduction was confirmed by the results of surface coverage, biomass and protein
      accumulation. The HPLC spectrum of the spent culture with vanillin addition
      showed that vanillin may interfere with quorum sensing molecules and thus prevent
      the formation of the biofilms. 

PMID- 23539152
TI  - Accelerated removal of Sudan dye by Shewanella oneidensis MR-1 in the presence of
      quinones and humic acids.
AB  - Although there have been many studies on bacterial removal of soluble azo dyes,
      much less information is available for biological treatment of water-insoluble
      azo dyes. The few bacterial species capable of removing Sudan dye generally
      require a long time to remove low concentrations of insoluble dye particles. The
      present work examined the efficient removal of Sudan I by Shewanella oneidensis
      MR-1 in the presence of redox mediator. It was found that the microbially reduced
      anthraquinone-2,6-disulfonate (AQDS) could abiotically reduce Sudan I, indicating
      the feasibility of microbially-mediated reduction. The addition of 100 MUM AQDS
      and other different quinone compounds led to 4.3-54.7 % increase in removal
      efficiencies in 22 h. However, adding 5-hydroxy-1,4-naphthoquinone into the
      system inhibited Sudan I removal. The presence of 10, 50 and 100 MUM AQDS
      stimulated the removal efficiency in 10 h from 26.4 to 42.8, 54.9 and 64.0 %,
      respectively. The presence of 300 MUM AQDS resulted in an eightfold increase in
      initial removal rate from 0.19 to 1.52 mg h-1 g-1 cell biomass. A linear
      relationship was observed between the initial removal rates and AQDS
      concentrations (0-100 MUM). Comparison of Michaelis-Menten kinetic constants
      revealed the advantage of AQDS-mediated removal over direct reduction. Different
      species of humic acid could also stimulate the removal of Sudan I. Scanning
      electronic microscopy analysis confirmed the accelerated removal performance in
      the presence of AQDS. These results provide a potential method for the efficient
      removal of insoluble Sudan dye.

PMID- 23539153
TI  - Transcriptome-wide identification of R2R3-MYB transcription factors in barley
      with their boron responsive expression analysis.
AB  - MYB family of transcription factors (TF) comprises one of the largest
      transcription factors in plants and is represented in all eukaryotes. They
      include highly conserved MYB repeats (1R, R2R3, 3R, and 4R) in the N-terminus. In
      addition to this, they have diverse C-terminal sequences which help the protein
      gain wide distinct functions, such as controlling development, secondary
      metabolism, hormonal regulation and response to biotic and abiotic stress. Stress
      responsive roles of the MYB TFs were reported for drought, salt, wounding, cold,
      freezing, dehydration and osmotic stresses. This study describes the
      identification of barley R2R3-MYB TFs including their expression analysis in
      tissues under control and Boron (B) toxic conditions. Conserved motifs for MYB
      proteins were searched into barley full-transcriptome RNA-seq data and a total of
      320 protein sequences were filtered as MYB TFs in which 51 of them corresponded
      to R2R3 MYB TFs. Using various bioinformatics tools, their conserved domain
      structures, chromosomal distributions, gene duplications, comparative functional
      analysis, as well as phylogenetic relations with Arabidopsis thaliana, were
      conducted. Beside the RNA-seq data-based expression pattern analysis of 51 R2R3
      MYB TFs, quantitative analysis of selected R2R3 MYB TF genes was assessed in
      control and B-stressed root and leaf tissues. Critical B-induced R2R3 MYB TFs
      were identified. It was concluded that the results would be useful for functional
      characterizations of R2R3-type MYB transcription factors that are possibly
      involved in both B stress and divergent regulation mechanisms in plants.

PMID- 23539155
TI  - Cross specialty training would improve outlook for academic psychiatry, says
      report.

PMID- 23539156
TI  - Fibrotic focus in breast carcinomas: relationship with prognostic parameters and
      biomarkers.
AB  - BACKGROUND: Fibrotic focus (FF) has been observed in breast cancers and is
      suggested to be an important prognostic marker. However, most of these
      observations were reported by the same group of investigators with similar sample
      cohort. The relationship of FF and molecular subtypes as well as its associated
      prognosis has not been elucidated. METHODS: In this study, 450 cases of breast
      carcinomas were evaluated for the presence of FF and its association with
      clinicopathologic parameters and biomarkers. RESULTS: FF was found in 18.7% of
      all consecutive cases. FF was associated positively with infiltrative margins
      (p=0.03) but negatively with extensive in situ component (p<0.001) and
      lymphocytic infiltration (p<0.001). It was positively associated with estrogen
      receptor (p=0.007) but negatively with human epidermal growth factor receptor 2
      (HER2; p=0.001), epidermal growth factor receptor (p=0.021), Ki-67 (p=0.001), and
      c-kit (p=0.009). Concomitantly, FF was seen more commonly in luminal A cancers
      (p<0.001) but less so in luminal B (p=0.045) and HER2-overexpressing cancers
      (p=0.011). Analysis on patient outcome (median 41 months, range 1-69 months)
      indicated that FF was an independent poor prognostic factor for disease-free
      survival (hazard ratio=2.57; 95% confidence interval=1.267-5.214, p=0.009),
      particularly in the luminal B subtype. CONCLUSIONS: The findings suggested that
      FF is associated with specific tumor morphology of an infiltrative, stellate
      pattern (typical invasive ductal carcinoma-not otherwise specified) rather than
      round, cellular mass with intense lymphocytic infiltrate (basal-like breast
      cancers). The poor prognostic implication of FF is additional and independent of
      other adverse prognostic indicators.

PMID- 23539158
TI  - The burden of poofs: criminal pathology, clinical scrutiny, and homosexual
      etiology in queer cinema.
AB  - Given the resurgence of scientific studies on the etiology of homosexuality in
      the wake of the AIDS epidemic, this article considers the effects these studies
      had on contemporaneous queer filmmakers. By using the subject of criminality as a
      way to talk about homosexual causality, queer films of the 1990s illustrate that
      contemporary scientific studies on homosexuality were historically and
      politically situated in relation to cultural anxieties about other forms of
      deviance. This article focuses on films that dissect the hetero-normative
      tendency to amalgamate forms of deviance in order to distinguish between the
      diseased and the healthy. Such products of New Queer Cinema highlight this
      amalgamation of criminality and homosexuality in order to challenge demands by
      the LGBT community of the 1980s and 1990s for "more positive images" in film.
      This article argues that queer filmmakers have manipulated the image of the queer
      criminal to usurp the medical tendency to biologize and pathologize the notion of
      queer transgression. In such a way, queer films that enthusiastically dramatize
      the queer outlaw perpetuate myths about homosexuality in order to dissect and
      discredit them.

PMID- 23539154
TI  - The wobbler mouse, an ALS animal model.
AB  - This review article is focused on the research progress made utilizing the
      wobbler mouse as animal model for human motor neuron diseases, especially the
      amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive
      degeneration of upper and lower motor neurons and shows striking similarities to
      ALS. The cellular effects of the wobbler mutation, cellular transport defects,
      neurofilament aggregation, neuronal hyperexcitability and neuroinflammation
      closely resemble human ALS. Now, 57 years after the first report on the wobbler
      mouse we summarize the progress made in understanding the disease mechanism and
      testing various therapeutic approaches and discuss the relevance of these
      advances for human ALS. The identification of the causative mutation linking the
      wobbler mutation to a vesicle transport factor and the research focussed on the
      cellular basis and the therapeutic treatment of the wobbler motor neuron
      degeneration has shed new light on the molecular pathology of the disease and
      might contribute to the understanding the complexity of ALS.

PMID- 23539159
TI  - Beta-blocker management of refractory hemoptysis in cystic fibrosis: a novel
      treatment approach.
AB  - BACKGROUND: /objective: Recurrent hemoptysis is a debilitating complication of
      cystic fibrosis (CF) and likely results from mucosal erosions into abnormal
      bronchial blood vessels due to chronic respiratory infection. We hypothesize that
      the use of beta-blockade will decrease mean arterial pressure resulting in lower
      bronchial artery blood flow and, subsequently, decrease the frequency and
      severity of hemoptysis, rate of hospitalizations, and usage of intravenous
      antibiotics. METHODS: Retrospective chart review was performed on 12 CF patients
      with recurrent hemoptysis, aged 13-40 years old, along with a follow-up telephone
      survey to assess the effectiveness of beta-blockade for hemoptysis, tolerance of
      inhaled respiratory medications, activity tolerance, and potential adverse
      effects. A beta-blocker, specifically atenolol, was initiated in all subjects
      within 24 hours after experiencing recurrent hemoptysis episodes. RESULTS: A
      majority of patients (72.7%) had complete cessation of hemoptysis. There were
      significant decreases in the frequency of hemoptysis (p = 0.02) and the amount of
      hemoptysis (p = 0.004). The rate of hospitalizations significantly decreased from
      1.33 to 0.67 (p = 0.05) after initiation of atenolol. There was a trend toward
      statistical significance in the reduction of intravenous antibiotics use (p =
      0.08). No statistical difference was found when comparing the pre- and post
      treatment means of forced expiratory volume in 1-second (p = 0.59). Very minimal
      adverse effects were observed with only one patient reporting intermittent facial
      flushing. CONCLUSION: Beta-blockade, particularly with atenolol, appears to
      successfully treat, if not resolve, recurrent hemoptysis refractory to
      conservative therapy in CF. Beta-blocker therapy appears to maintain an effective
      safety profile in CF.

PMID- 23539160
TI  - Investigating ophthalmology with translational science: the Weisenfeld Lecture.

PMID- 23539161
TI  - Some principles of retinal design: the Proctor lecture.

PMID- 23539162
TI  - The pathogenesis of glaucoma in the interplay with the immune system.
AB  - Glaucoma was previously thought to be caused only through an elevated intraocular
      pressure as a sole trigger. Emerging evidence indicates that the pathogenesis of
      glaucoma depends on several interacting pathogenetic mechanisms, which include
      mechanical effects by an increased IOP, decreased neutrophine-supply, hypoxia,
      excitotoxicity, oxidative stress and the involvement of autoimmune processes.
      These autoimmune processes within the central nervous system are a highly
      organized response of the innate immunity. Through the recognition of neuronal
      epitopes, the long-term induction of the innate immune response and its
      transition to an adaptive form might be central to the pathophysiology of the
      glaucoma disease. Regardless of the pathogenic mechanism, the consequences are
      always the establishment of extensive degenerative processes in the optic nerve
      head, the retinal ganglion cells and the axons of the optic nerve, which will
      lead in the irreversible destruction of these neurons. This review article
      summarizes the current knowledge concerning the pathogenesis of glaucoma, with
      special focus on its interplay with the immune system.

PMID- 23539163
TI  - Retinal neurovascular and neuronal dysfunction in type 1 diabetes.

PMID- 23539164
TI  - Introducing John V. Forrester, the 2012 recipient of the Weisenfeld award.

PMID- 23539165
TI  - Introducing Peter Sterling, the 2012 recipient of the Proctor Medal.

PMID- 23539166
TI  - A role for systemic inflammation in diabetic retinopathy.

PMID- 23539167
TI  - Endoscopy-assisted percutaneous repair of acute Achilles tendon tears.
AB  - BACKGROUND: We developed a technique for endoscopy-assisted percutaneous repair
      of acute Achilles tendon tears. METHODS: Nineteen patients with acute Achilles
      tendon tears were prospectively recruited into the study. All patients (18 male,
      1 female) had sports-related injuries. Preoperative diagnosis was made from
      patient history, physical examination, and sonography. The average patient age
      was 38.7 years, and follow-up averaged 24 months. All patients received endoscopy
      assisted percutaneous Achilles tendon repair with modified Bunnell sutures passed
      by bird beak and No. 5 Ethibond under direct visualization using 4.0-mm
      arthroscopy. Results were evaluated by physical examination, sonography, and
      magnetic resonance imaging (MRI). RESULTS: All 19 patients achieved tendon
      healing. All patients were evaluated by sonography, and the tendons of 16
      patients were imaged using MRI to evaluate the extent of healing. Final
      dorsiflexion was 16 degrees and plantar flexion 26 degrees, and 95% of the
      patients (18/19) returned to their previous level of sporting activity. One
      patient developed a superficial infection, and 2 patients had postoperative sural
      nerve injury with numbness for 1 month. There were no other major complications.
      CONCLUSION: Endoscopy-assisted percutaneous repair of the Achilles tendon allowed
      good tendon healing and return to sports at 6 months. Sural nerve injury during
      surgery was a potential complication of this procedure. LEVEL OF EVIDENCE: Level
      IV, retrospective case series.

PMID- 23539168
TI  - A biomechanical analysis of two anterior ankle arthrodesis systems.
AB  - BACKGROUND: An increasingly popular ankle fusion method uses plates and screws
      positioned on the anterior aspect of the tibiotalar joint. This study compared
      the mechanical properties of 2 contemporary plate systems for ankle arthrodesis,
      one based on a single anterior plate and the other comprising paired anteromedial
      and anterolateral plates. METHODS: Ten matched pairs of fresh-frozen cadaver
      ankle joints underwent arthrodesis with a single anatomically contoured anterior
      plate or 2 anatomic plates applied anteromedially and anterolaterally. Each
      arthrodesed specimen was subjected to controlled sagittal and coronal plane
      bending and internal and external rotation. Tibiotalar joint bending stiffness,
      bending angulation, torsional stiffness, and joint rotation were documented.
      RESULTS: Bending stiffness of the 2-plate system was 1.5 to 5 times greater than
      that of the single-plate system in plantarflexion, dorsiflexion, eversion, and
      inversion (P = .005-.050). Angulation in each bending direction was several-fold
      greater than for the single plate (P = .005-.014) at the peak applied moment.
      Torsional stiffness of the 2-plate system nearly doubled that of the single plate
      in both rotation directions (P = .014, P = .005). Approximately half as much
      arthrodesis site rotation occurred with 2-plate fixation at the peak applied
      torque (P = .005, P = .007). CONCLUSION: The tested 2-plate arthrodesis system
      has the potential to optimize arthrodesis site stiffness compared with fixation
      with a contemporary single plate. CLINICAL RELEVANCE: Use of the stiffer 2-plate
      system could improve the clinical fusion rate, especially in patients with
      suboptimal bone quality.

PMID- 23539169
TI  - Electrodiagnostically confirmed posttraumatic neuropathy and associated clinical
      exam findings with lisfranc injury.
AB  - BACKGROUND: Patients with a Lisfranc injury often complain of persistent pain
      radiating from the Lisfranc joint up or down the first dorsal web space,
      accompanied by decreased sensation. We hypothesized that these symptoms were
      related to a posttraumatic neuropathy of the terminal medial branch of deep
      fibular (peroneal) nerve (MBDFN) and that by recognizing this symptom an earlier
      diagnosis of Lisfranc injury may be possible. METHODS: Twelve patients with
      diagnosis of subtle unilateral Lisfranc injury, confirmed by standing X-ray, CT,
      or bone scan, were enrolled. Standardized antidromic sensory nerve conduction
      studies of MBDFN were performed bilaterally within 2 months postinjury and prior
      to surgical intervention. The contralateral, normal side was used as a control.
      All patients were tested for decreased 2-point discrimination in the first dorsal
      web space on both lower extremities. RESULTS: Sensory nerve action potential of
      the MBDFN was absent, with decreased 2-point discrimination on the injured side
      in all patients. CONCLUSION: Lisfranc injuries were associated with a
      posttraumatic neuropathy of the MBDFN and decreased 2-point discrimination in the
      first dorsal web space. The finding of altered sensation in the first dorsal web
      space may help the practitioner to earlier diagnosis of a Lisfranc injury. LEVEL
      OF EVIDENCE: Level III, case control study.

PMID- 23539170
TI  - Pharmacogenetics in cardiovascular disorders: an update on the principal drugs.
AB  - In the coming years, genomics will impact clinical practice in multiple ways.
      However, one of the most important applications will be in the determination of
      the best treatments in personalized medicine. This is, in fact, one of the fields
      in which genetic variants have already been most successful and useful to
      clinicians. Here, we briefly review the current state of the art on
      pharmacogenomics and its applications to modern cardiovascular medicine.

PMID- 23539171
TI  - Lymphangioleiomyomatosis screening in women with tuberous sclerosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) occurs in at least 40% of women with
      tuberous sclerosis complex (TSC), as diagnosed based on chest CT scan findings.
      Early identification may inform lifestyle choices and treatment decisions. Here
      we report LAM prevalence in a large TSC clinic and propose an approach to CT scan
      screening for LAM in women with TSC. METHODS: We retrospectively reviewed initial
      chest CT scans of all female patients with TSC aged >= 15 years seen at our
      center over a 12-year period. Each CT image slice was manually scored for the
      presence or absence of characteristic thin-walled cysts, and the diagnosis of LAM
      was made if the sum of the cysts on all slices exceeded three cysts. RESULTS: Of
      133 female patients with TSC, 101 had chest CT scans available for review. Forty
      eight (47.5%) met criteria for TSC-LAM on the initial CT scan. The risk of LAM
      was age dependent, rising by about 8% per year. The prevalence of LAM was 27% in
      subjects < 21 years of age and 81% in subjects > 40 years of age. Among
      asymptomatic subjects with LAM, 84% had cysts present in the single image at the
      level of the carina. Most subjects with LAM eventually developed pulmonary
      symptoms (63%), and 12.5% died from LAM. CONCLUSIONS: These results suggest that
      most women with TSC ultimately develop cystic changes consistent with LAM and
      that most cases can be identified from a single CT imaging slice at the level of
      the carina. TSC-LAM was associated with appreciable morbidity and mortality in
      this referral population. An age-based approach using limited CT scanning methods
      may facilitate screening and subsequent treatment decisions with decreased
      radiation exposure in this at-risk population.

PMID- 23539172
TI  - Feasibility of lactadherin-bearing clinically available microbubbles as
      ultrasound contrast agent for angiogenesis.
AB  - OBJECTIVES: Phagocytosis of apoptotic cells is carried out through bridging of
      phosphatidylserine (PS)-expressing apoptotic cells and integrin alphavbeta3
      expressing phagocytes with lactadherin. The objective of this study was to
      examine whether microbubbles targeted to integrin alphavbeta3 could be produced
      by conjugating a PS-containing clinically available ultrasound contrast agent
      with lactadherin. MATERIALS AND METHODS: PS-containing perfluorobutane-filled
      microbubbles were incubated with R-phycoerythrin (PE)-labeled lactadherin, and
      the presence of PE-positive bubbles was examined by FACS analysis. Secondly, the
      attachment of lactadherin to integrin alphavbeta3-expressing cells (human
      umbilical vein endothelial cells (HUVEC)) was also examined by FACS analysis.
      Finally, the adhesion of PS-containing bubbles to HUVEC was examined using a
      parallel plate flow chamber. The number of adherent bubbles with or without the
      intermediation of lactadherin was compared. RESULTS: The more lactadherin was
      added to the bubble suspension, the more PE-positive bubbles were detected. The
      size of bubbles was not increased even after conjugation with lactadherin (2.90
      +/- 0.04 vs. 2.81 +/- 0.02 MUm). Binding between lactadherin and HUVEC was also
      confirmed by FACS analysis. The parallel plate flow chamber study revealed that
      the number of PS-containing bubbles adherent to HUVEC was increased about five
      times by the intermediation of lactadherin (12.1 +/- 6.0 to 58.7 +/- 33.1
      bubbles). CONCLUSION: Because integrin alphavbeta3 is well-known to play a key
      role in angiogenesis, the complex of PS-containing bubbles and lactadherin has
      feasibility as a clinically translatable targeted ultrasound contrast agent for
      angiogenesis.

PMID- 23539173
TI  - Effect of suturing the femoral portion of a four-strand graft during an ACL
      reconstruction.
AB  - PURPOSE: A suture passed along the part of the graft that will be inserted into
      the femoral tunnel is widely used by surgeons, because it could prevent the graft
      sliding on the femoral fixation device during pulling from the tibial side. The
      aim of this study was to evaluate the biomechanical effects of suturing the
      intratunnel femoral part of the graft during an anterior cruciate ligament (ACL)
      reconstruction. METHODS: Bovine digital extensor tendons and tibias were
      harvested from 20 fresh-frozen mature bovine knees ranging in age from 18 to 24
      months. Quadruple-strand bovine tendons were passed through the tibial tunnel and
      secured distally with a bioabsorbable interference screw. In one half of all
      grafts (N = 10), the looped-over part of the graft was sutured in a whipstitch
      technique over a distance of 30 mm (Group 1). In one half of all grafts (N = 10),
      the looped-over part was left free from any suture (Group 2). The grafts were
      preconditioned at 50 N for 10 min, followed by cyclic loading at 1 Hz between 50
      N and 250 N for 1,000 cycles. Load-to-failure test was then carried out at a rate
      of 1 mm/s. RESULTS: There was no statistically significant difference between
      mean stiffness at pullout and yield load between the two groups. In all specimens
      on Group 1, failure occurred following to partial breaking and then slipping of
      the tendons between the screw and the tunnel. Concerning Group 2, in six cases
      failure occurred as described for Group 1 specimens. In the remaining four cases,
      failure occurred entirely through the ligament mid-substance. CONCLUSIONS:
      Suturing in a whipstitch fashion the femoral portion of the graft doesn't affect
      the mechanical proprieties of the ACL graft. When suspension fixation device is
      used, suturing the looped-over part of the graft could be helpful in order to
      provide equal tension in all of the strands of the graft at time of tibial
      fixation.

PMID- 23539174
TI  - Meta-analysis of the association between secondhand smoke exposure and physician
      diagnosed childhood asthma.
AB  - INTRODUCTION: Studies suggest an association between secondhand smoke exposure
      and the development of childhood asthma. Several countries are considering
      legislation to protect children from exposure. METHODS: A systematic review was
      conducted using MEDLINE, Embase, PubMed, and Web of Knowledge databases and a
      random effects meta-analysis was undertaken. Heterogeneity was assessed using the
      I (2) test. Publication and small study biases were examined visually using a
      funnel plot and tested formally using Egger test. Univariate and multivariate
      meta-regression analyses were undertaken, including a subgroup analysis of cohort
      studies to examine the effect of duration of follow-up. RESULTS: Twenty relevant
      studies were identified (14 cross-sectional, 4 cohort, and 2 case-control) and
      provided 31 estimates of effect size. The pooled odds ratio was 1.32 (95% CI:
      1.23, 1.42, p < .001). There was moderate heterogeneity (I (2) = 74.2%, p <
      .001). On multivariate meta-regression analysis, effect size estimates were
      significantly higher for case-control studies (p = .042) and those using self
      reported exposure to secondhand smoke (p = .050). There was no evidence of
      significant publication or small study bias (Egger test, p = .121). CONCLUSIONS:
      There is now consistent evidence of a modest association between secondhand smoke
      and physician-diagnosed childhood asthma. These results lend support to continued
      efforts to reduce childhood exposure to secondhand smoke.

PMID- 23539175
TI  - Influence of selected b values on ADC quantification in diffusion-weighted MRI.
      Comment on Punwani et al.: Diffusion-weighted MRI of lymphoma: prognostic utility
      and implications for PET/MRI?

PMID- 23539176
TI  - Accuracy of ADC estimates: response to letter by Priola et al. re Diffusion
      weighted MRI of lymphoma: prognostic utility and implications for PET/MRI?

PMID- 23539177
TI  - Discrepant uptake of the radiolabeled norepinephrine analogues hydroxyephedrine
      (HED) and metaiodobenzylguanidine (MIBG) in rat hearts.
AB  - PURPOSE: (11)C-Hydroxyephedrine (HED) and radioiodinated metaiodobenzylguanidine
      ((123)I/(131)I-MIBG) are catecholamine analogue tracers for sympathetic nerve
      positron emission tomography/single photon emission computed tomography
      (PET/SPECT) imaging. In contrast to humans, rat hearts demonstrate high nonneural
      catecholamine uptake-2 in addition to neural uptake-1, the contributions of which
      to tracer accumulation are not fully elucidated. METHODS: Wistar rats were
      studied using the following pretreatments: uptake-1 blockade with desipramine 2
      mg/kg IV, both uptake-1 and -2 blockade with phenoxybenzamine 50 mg/kg IV, or
      control with saline IV. HED or (123)I-MIBG was injected 10 min after
      pretreatment, and rats were sacrificed 10 min later. Heart to blood tissue count
      ratio (H/B ratio) was obtained using a gamma counter. To determine regional
      tracer uptake, dual-tracer autoradiography was performed with HED and (131)I-MIBG
      in Wistar rats with chronic infarction by transient coronary occlusion and
      reperfusion and in healthy control rats. Local tracer distributions were
      analyzed, and the infarcted rats' local tracer distributions were compared with
      histology. RESULTS: The H/B ratios in control hearts were 34.4 +/- 1.7 and 25.5
      +/- 2.1 for HED and (123)I-MIBG, respectively. Desipramine led to a significant
      decrease in HED (3.2 +/- 0.5, p < 0.0001), while there was no change in (123)I
      MIBG (25.5 +/- 6.4, p = n.s.). Phenoxybenzamine led to a significant decrease in
      both HED and (123)I-MIBG (3.5 +/- 0.02, 4.3 +/- 0.7, p < 0.0001). Only HED showed
      a subepicardium-subendocardium gradient in healthy control hearts which is
      consistent with physiological innervation, while (131)I-MIBG was evenly
      distributed throughout the myocardium. (131)I-MIBG uptake defect closely matched
      the scar area determined by histology [3.8 +/- 2.3% ((131)I-MIBG defect) vs 4.0
      +/- 2.4% (scar)]. However, the scar area was clearly exceeded by the HED uptake
      defect (9.1 +/- 2.2%, p < 0.001). CONCLUSION: HED uptake showed high specificity
      to neural uptake-1 in rat hearts. On the other hand, (123)I/(131)I-MIBG
      demonstrated distinct characters of regional tracer distribution and uptake
      mechanism that are compatible with significant contribution of nonneural uptake
      2.

PMID- 23539178
TI  - Amplifying genetic logic gates.
AB  - Organisms must process information encoded via developmental and environmental
      signals to survive and reproduce. Researchers have also engineered synthetic
      genetic logic to realize simpler, independent control of biological processes. We
      developed a three-terminal device architecture, termed the transcriptor, that
      uses bacteriophage serine integrases to control the flow of RNA polymerase along
      DNA. Integrase-mediated inversion or deletion of DNA encoding transcription
      terminators or a promoter modulates transcription rates. We realized permanent
      amplifying AND, NAND, OR, XOR, NOR, and XNOR gates actuated across common control
      signal ranges and sequential logic supporting autonomous cell-cell communication
      of DNA encoding distinct logic-gate states. The single-layer digital logic
      architecture developed here enables engineering of amplifying logic gates to
      control transcription rates within and across diverse organisms.

PMID- 23539179
TI  - Global leaf trait relationships: mass, area, and the leaf economics spectrum.
AB  - The leaf economics spectrum (LES) describes multivariate correlations that
      constrain leaf traits of plant species primarily to a single axis of variation if
      data are normalized by leaf mass. We show that these traits are approximately
      distributed proportional to leaf area instead of mass, as expected for a light-
      and carbon dioxide-collecting organ. Much of the structure in the mass-normalized
      LES results from normalizing area-proportional traits by mass. Mass normalization
      induces strong correlations among area-proportional traits because of large
      variation among species in leaf mass per area (LMA). The high LMA variance likely
      reflects its functional relationship with leaf life span. A LES that is
      independent of mass- or area-normalization and LMA reveals physiological
      relationships that are inconsistent with those in global vegetation models
      designed to address climate change.

PMID- 23539180
TI  - Photochemical route for accessing amorphous metal oxide materials for water
      oxidation catalysis.
AB  - Large-scale electrolysis of water for hydrogen generation requires better
      catalysts to lower the kinetic barriers associated with the oxygen evolution
      reaction (OER). Although most OER catalysts are based on crystalline mixed-metal
      oxides, high activities can also be achieved with amorphous phases. Methods for
      producing amorphous materials, however, are not typically amenable to mixed-metal
      compositions. We demonstrate that a low-temperature process, photochemical metal
      organic deposition, can produce amorphous (mixed) metal oxide films for OER
      catalysis. The films contain a homogeneous distribution of metals with
      compositions that can be accurately controlled. The catalytic properties of
      amorphous iron oxide prepared with this technique are superior to those of
      hematite, whereas the catalytic properties of a-Fe(100-y-z)Co(y)Ni(z)O(x) are
      comparable to those of noble metal oxide catalysts currently used in commercial
      electrolyzers.

PMID- 23539181
TI  - Rational HIV immunogen design to target specific germline B cell receptors.
AB  - Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV
      1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding
      site of HIV gp120 have been isolated from HIV-1-infected individuals; however,
      such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack
      detectable affinity for predicted germline precursors of VRC01-class bNAbs,
      making them poor immunogens to prime a VRC01-class response. We employed
      computation-guided, in vitro screening to engineer a germline-targeting gp120
      outer domain immunogen that binds to multiple VRC01-class bNAbs and germline
      precursors, and elucidated germline binding crystallographically. When
      multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and
      mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine
      prime. In principle, germline-targeting strategies could be applied to other
      epitopes and pathogens.

PMID- 23539182
TI  - Atmosphere. Irreversible does not mean unavoidable.

PMID- 23539183
TI  - Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric
      glioblastoma.
AB  - Sequencing of pediatric gliomas has identified missense mutations Lys27Met (K27M)
      and Gly34Arg/Val (G34R/V) in genes encoding histone H3.3 (H3F3A) and H3.1
      (HIST3H1B). We report that human diffuse intrinsic pontine gliomas (DIPGs)
      containing the K27M mutation display significantly lower overall amounts of H3
      with trimethylated lysine 27 (H3K27me3) and that histone H3K27M transgenes are
      sufficient to reduce the amounts of H3K27me3 in vitro and in vivo. We find that
      H3K27M inhibits the enzymatic activity of the Polycomb repressive complex 2
      through interaction with the EZH2 subunit. In addition, transgenes containing
      lysine-to-methionine substitutions at other known methylated lysines (H3K9 and
      H3K36) are sufficient to cause specific reduction in methylation through
      inhibition of SET-domain enzymes. We propose that K-to-M substitutions may
      represent a mechanism to alter epigenetic states in a variety of pathologies.

PMID- 23539184
TI  - Obesity-related genetic variants, human pigmentation, and risk of melanoma.
AB  - Previous biological studies showed evidence of a genetic link between obesity and
      pigmentation in both animal models and humans. Our study investigated the
      individual and joint associations between obesity-related single nucleotide
      polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight
      obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3
      genes were nominally significantly associated with hair color among 5,876
      individuals of European ancestry. The genetic score combining 35 independent
      obesity-risk loci was significantly associated with darker hair color (beta
      coefficient per ten alleles = 0.12, P value = 4 * 10(-5)). However, single SNPs
      or genetic scores showed non-significant association with tanning ability. We
      further examined the SNPs at the FTO locus for their associations with
      pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with
      imputation R (2) quality metric >0.8 using the 1,000 genome data set, ten and
      three independent SNPs were significantly associated with hair color and tanning
      ability respectively. Moreover, five independent FTO SNPs showed nominally
      significant association with risk of melanoma in 1,804 cases and 1,026 controls.
      But none of them was associated with obesity or in linkage disequilibrium with
      obesity-related variants. FTO locus may confer variation in human pigmentation
      and risk of melanoma, which may be independent of its effect on obesity.

PMID- 23539185
TI  - Community empowerment among female sex workers is an effective HIV prevention
      intervention: a systematic review of the peer-reviewed evidence from low- and
      middle-income countries.
AB  - We conducted a systematic review and meta-analysis of community empowerment
      interventions for HIV prevention among sex workers in low- and middle-income
      countries from 1990-2010. Two coders abstracted data using standardized forms. Of
      6,664 citations screened, ten studies met inclusion criteria. For HIV infection,
      two observational studies showed a significantly protective combined effect [odds
      ratio (OR): 0.84, 95% confidence interval (CI): 0.709-0.988]. For STI infection,
      one longitudinal study showed reduced gonorrhoea/chlamydia (OR: 0.51, 95% CI:
      0.26-0.99). Observational studies showed reduced gonorrhoea (OR: 0.65, 95% CI:
      0.47-0.90), but non-significant effects on chlamydia and syphilis. For condom
      use, one randomized controlled trial showed improvements with clients (beta:
      0.3447, p = 0.002). One longitudinal study showed improvements with regular
      clients (OR: 1.9, 95% CI: 1.1-3.3), but no change with new clients. Observational
      studies showed improvements with new clients (OR: 3.04, 95% CI: 1.29-7.17),
      regular clients (OR: 2.20, 95% CI: 1.41-3.42), and all clients (OR: 5.87, 95% CI:
      2.88-11.94), but not regular non-paying partners. Overall, community empowerment
      based HIV prevention was associated with significant improvements across HIV
      outcomes and settings.

PMID- 23539186
TI  - Determinants of HIV infection among female sex workers in two cities in the
      Republic of Moldova: the role of injection drug use and sexual risk.
AB  - In 2009-2010, females who reported having vaginal, anal or oral sex in exchange
      for money in the previous year, >=16 years, and living in either Chisinau (n =
      299) or Balti (n = 359), Moldova, were recruited into a respondent driven
      sampling survey. One fifth reported ever injecting drugs and over 30 % ever had
      sexual intercourse with men who inject drugs. In both cities, condom use with
      permanent and casual partners was much lower than condom use with commercial
      partners. In Chisinau, 6.9 % and in Balti, 24.7 % tested positive for HIV; 18 and
      23.7 % had antibodies to hepatitis C; 9.1 and 8.9 % had antibodies to HBV; and,
      8.4 and 6.1 % tested positive for syphilis. HIV seropositive FSW in either city
      were more likely to have ever injected drugs and to be infected with HCV. Limited
      government initiative and drastic reductions in international funding will likely
      impact urgently needed HIV prevention and harm reduction services targeting FSW
      in Moldova.

PMID- 23539187
TI  - Posttraumatic stress symptoms among adults caring for orphaned children in HIV
      endemic South Africa.
AB  - There is growing evidence that mental health is a significant issue among
      families affected by AIDS-related parental deaths. The current study examined
      posttraumatic stress symptoms and identified risk factors among adults caring for
      AIDS-orphaned and other-orphaned children in an HIV-endemic South African
      community. A representative community sample of adults caring for children (N =
      1,599) was recruited from Umlazi Township. Of the 116 participants who reported
      that a traumatic event was still bothering them, 19 % reported clinically
      significant posttraumatic stress symptoms. Of the 116 participants, caregivers of
      AIDS-orphaned and other-orphaned children were significantly more likely to meet
      threshold criteria for PTSD (28 %) compared to caregivers of non-orphaned
      children (10 %). Household receipt of an old age pension was identified as a
      possible protective factor for PTSD symptoms among caregivers of orphaned
      children. Services are needed to address PTSD symptoms among caregivers of
      orphaned children.

PMID- 23539188
TI  - The impact of P-gp functionality on non-steady state relationships between CSF
      and brain extracellular fluid.
AB  - In the development of central nervous system (CNS)-targeted drugs, the prediction
      of human CNS target exposure is a big challenge. Cerebrospinal fluid (CSF)
      concentrations have often been suggested as a 'good enough' surrogate for brain
      extracellular fluid (brainECF, brain target site) concentrations in humans.
      However, brain anatomy and physiology indicates prudence. We have applied a
      multiple microdialysis probe approach in rats, for continuous measurement and
      direct comparison of quinidine kinetics in brainECF, CSF, and plasma. The data
      obtained indicated important differences between brainECF and CSF kinetics, with
      brainECF kinetics being most sensitive to P-gp inhibition. To describe the data
      we developed a systems-based pharmacokinetic model. Our findings indicated that:
      (1) brainECF- and CSF-to-unbound plasma AUC0-360 ratios were all over 100 %; (2)
      P-gp also restricts brain intracellular exposure; (3) a direct transport route of
      quinidine from plasma to brain cells exists; (4) P-gp-mediated efflux of
      quinidine at the blood-brain barrier seems to result of combined efflux
      enhancement and influx hindrance; (5) P-gp at the blood-CSF barrier either
      functions as an efflux transporter or is not functioning at all. It is concluded
      that in parallel obtained data on unbound brainECF, CSF and plasma
      concentrations, under dynamic conditions, is a complex but most valid approach to
      reveal the mechanisms underlying the relationship between brainECF and CSF
      concentrations. This relationship is significantly influenced by activity of P
      gp. Therefore, information on functionality of P-gp is required for the
      prediction of human brain target site concentrations of P-gp substrates on the
      basis of human CSF concentrations.

PMID- 23539190
TI  - Cost effectiveness of guanfacine extended-release versus atomoxetine for the
      treatment of attention-deficit/hyperactivity disorder: application of a matching
      adjusted indirect comparison.

PMID- 23539189
TI  - Magnetic resonance imaging evidence for presymptomatic change in thalamus and
      caudate in familial Alzheimer's disease.
AB  - Amyloid imaging studies of presymptomatic familial Alzheimer's disease have
      revealed the striatum and thalamus to be the earliest sites of amyloid
      deposition. This study aimed to investigate whether there are associated volume
      and diffusivity changes in these subcortical structures during the presymptomatic
      and symptomatic stages of familial Alzheimer's disease. As the thalamus and
      striatum are involved in neural networks subserving complex cognitive and
      behavioural functions, we also examined the diffusion characteristics in
      connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers
      underwent volumetric and diffusion tensor magnetic resonance imaging,
      neuropsychological and clinical assessments; 10 were symptomatic, 10 were
      presymptomatic and on average 5.6 years younger than their expected age at onset;
      20 healthy control subjects were also studied. We conducted region of interest
      analyses of volume and diffusivity changes in the thalamus, caudate, putamen and
      hippocampus and examined diffusion behaviour in the white matter tracts of
      interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and
      tract-based spatial statistics were also used to provide unbiased whole-brain
      analyses of group differences in volume and diffusion indices, respectively. We
      found that reduced volumes of the left thalamus and bilateral caudate were
      evident at a presymptomatic stage, together with increased fractional anisotropy
      of bilateral thalamus and left caudate. Although no significant hippocampal
      volume loss was evident presymptomatically, reduced mean diffusivity was observed
      in the right hippocampus and reduced mean and axial diffusivity in the right
      cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial
      and in particular radial diffusivity, with reduced fractional anisotropy, in all
      of the white matter tracts of interest. The symptomatic group also showed atrophy
      and increased mean diffusivity in all of the subcortical grey matter regions of
      interest, with increased fractional anisotropy in bilateral putamen. We propose
      that axonal injury may be an early event in presymptomatic Alzheimer's disease,
      causing an initial fall in axial and mean diffusivity, which then increases with
      loss of axonal density. The selective degeneration of long-coursing white matter
      tracts, with relative preservation of short interneurons, may account for the
      increase in fractional anisotropy that is seen in the thalamus and caudate
      presymptomatically. It may be owing to their dense connectivity that imaging
      changes are seen first in the thalamus and striatum, which then progress to
      involve other regions in a vulnerable neuronal network.

PMID- 23539191
TI  - The Effects of Childhood Health on Adult Health and SES in China.
AB  - In this paper, we model the associations of childhood health on adult health and
      socio-economic status outcomes in China using a new sample of middle aged and
      older Chinese respondents. Modeled after the American Health and Retirement
      Survey (HRS), the CHARLS Pilot survey respondents are 45 years and older in two
      quite distinct provinces-Zhejiang, a high growth industrialized province on the
      East Coast and Gansu, a largely agricultural and poor province in the West.
      Childhood health in CHARLS relies on two measures that proxy for different
      dimensions of health during the childhood years. The first is a retrospective
      self-evaluation using a standard five-point scale (excellent, very good, good,
      fair, or poor) of general state of one's health when one was less than 16 years
      old. The second is adult height believed to be a good measure of levels of
      nutrition during early childhood and the prenatal period. We relate both these
      childhood health measures to adult health and SES outcomes during the adult
      years. We find strong associations of childhood health on adult health outcomes
      particularly among Chinese women and strong associations with adult BMI
      particularly for Chinese men.

PMID- 23539192
TI  - Retrospective study using the propensity score to clarify the oncologic
      feasibility of thoracoscopic esophagectomy in patients with esophageal cancer.
AB  - BACKGROUND: The present study aimed to clarify the long-term prognostic impact
      and oncologic feasibility of thoracoscopic esophagectomy (TSE) in patients with
      esophageal cancer in comparison with open thoracic esophagectomy (OTE). METHODS:
      Patients with esophageal cancer underwent surgically curative esophagectomy
      without neoadjuvant therapy from January 1991 to December 2008 and were analyzed
      retrospectively. Of 257 patients, 91 underwent TSE and 166 had OTE. Relations
      between the long-term prognosis after surgery, the surgical procedure, and
      clinicopathologic parameters were analyzed statistically. The propensity scores
      were calculated for all patients through a multiple logistic regression model
      that was optimized with Akaike's Information Criterion. Using Cox's proportional
      hazard model with prognostic variables and the propensity scores, we implemented
      a multivariate analysis for comparing the performance of two surgical methods.
      RESULTS: Patient characteristics and the incidence of perioperative morbidity or
      hospital death were similar for the TSE and OTE groups. Significantly more lymph
      nodes were dissected in the TSE group than in the OTE group (total p = 0.013;
      thoracic p = 0.0094; recurrent laryngeal p < 0.0001). The TSE group exhibited a
      more favorable prognosis after surgery than the OTE group in terms of overall
      survival (p = 0.011) and disease-specific survival (DSS) (p = 0.0040).
      Particularly in subgroup analysis of DSS, the TSE group had a favorable prognosis
      in upper thoracic esophageal cancer (p = 0.0053), invasive cancer (p = 0.046),
      node-positive cancer (p = 0.020), progressive cancer (p = 0.0052), cancer with
      lymphatic vessel invasion (p = 0.0019), and cancer without blood vessel invasion
      (p = 0.0081). In terms of DSS, the TSE group exhibited a more favorable prognosis
      than the OTE group regardless of the presence or absence of metastasis to lymph
      nodes around the thoracic (p < 0.0001) or recurrent laryngeal (p < 0.0001)
      nerves. TSE (p = 0.0430), lymph node metastasis (p = 0.0382), lymphatic invasion
      (p = 0.0418), and p stage (p = 0.0047) were independent prognostic parameters in
      the Cox's proportional hazard model with the propensity scores. CONCLUSIONS: TSE
      can contribute to prolonged survival after surgery in patients with esophageal
      cancer by enabling precise thoracic lymph node dissection based on a magnified
      surgical field. TSE might have maximum oncologic benefit and minimum invasiveness
      for patients with esophageal cancer.

PMID- 23539193
TI  - Lipocalin-2 is associated with a good prognosis and reversing epithelial-to
      mesenchymal transition in pancreatic cancer.
AB  - BACKGROUND: Lipocalin-2 is a multifaceted modulator in cancer progression. Its
      clinical significance is not clear in pancreatic cancer. The purpose of this
      study was to investigate whether lipocalin-2 is associated with good prognosis by
      reversing epithelial-to-mesenchymal transition (EMT) in pancreatic cancer.
      METHODS: Lipocalin-2, E-cadherin, or vimentin expression was detected in 60
      pancreatic adenocarcinoma specimens. Correlations between lipocalin-2 expression
      and EMT, the clinicopathologic characteristics, and prognosis were investigated.
      Whether pancreatic cancer cells' migration and invasion (some characteristics of
      EMT) were affected by lipocalin-2 was also explored. RESULTS: High lipocalin-2
      expression was significantly associated with a good prognosis in pancreatic
      cancer (p < 0.05). Overexpression of lipocalin-2 correlated with a lower extent
      of EMT (p < 0.05), increased E-cadherin expression (p < 0.05), decreased vimentin
      expression (p < 0.05), and reduced cancer cell migration and invasion in
      pancreatic cancer. CONCLUSIONS: Lipocalin-2 may be considered an epithelial
      inducer, which may reverse EMT and predict a good prognosis in pancreatic cancer.

PMID- 23539194
TI  - Early structured surgical management plan for neonates with short bowel syndrome
      may improve outcomes.
AB  - BACKGROUND: In children with short bowel syndrome, maximal adaptation of the
      bowel after extensive resection is thought to occur during the first 2 years of
      life. The aim of the present study was to review children with short bowel
      syndrome from two intestinal rehabilitation centers, comparing those undergoing
      lengthening procedures <365 days of age (early) versus those whose lengthening
      procedure was carried out >365 days of age (late). METHODS: Retrospective data
      collection was performed from January 2004 to December 2010 in Manchester, UK,
      and from December 2006 to December 2010 in Brussels, Belgium. Both medical
      centers follow a similar intestinal rehabilitation program (IRP). Data collected
      included population demographics, bowel length preoperatively and
      postoperatively, age at operation, parenteral nutrition (PN), central access, and
      complications. RESULTS: Complete data were available for eight children who
      underwent lengthening surgery at <365 days of age, and six who underwent the
      procedure at >365 days of age. Diagnoses were similar. Groups were matched for
      gestation and birthweight, with no statistical difference in preoperative and
      postoperative bowel lengths. The mean duration of PN postoperatively was 378 days
      in the early cohort and 589 days in the late cohort. This trended toward
      statistical significance (p = 0.071). Full enteral autonomy was achieved at 17
      months (early) and 59 months (late) (p = 0.01). Patients in the early group
      required fewer central lines than those operated on later (p = 0.035).
      CONCLUSIONS: Enrolling children into an IRP involving early (<365 days of age)
      lengthening surgery allows a shorter postoperative time to allow weaning to full
      enteral nutrition, as well as fewer central lines. Both outcomes provide benefits
      for the child and family, allowing an earlier return to normal life.

PMID- 23539195
TI  - Single-incision versus conventional laparoscopic cyst excision and Roux-Y
      hepaticojejunostomy for children with choledochal cysts: a case-control study.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of single-incision
      laparoscopic hepaticojejunostomy (SILH) with that of conventional laparoscopic
      hepaticojejunostomy (CLH) for children with choledochal cysts (CDCs). METHODS:
      Patients undergoing SILH between April 2011 and April 2012 were matched with
      those undergoing CLH between January 2009 and April 2011 for age, sex, CDC types,
      size, and operative surgeon. The operating time, postoperative hospital stay,
      time to full feed, postoperative complications, and perioperative laboratory
      tests were compared. RESULTS: A total of 150 patients (SILH 75, CLH 75) were
      evaluated. Median follow-up periods of SILH and CLH groups were 12 and 34 months,
      respectively. The postoperative hospital stay and time required for resumption of
      full diet were similar for the two groups (p = 0.93 and 0.16, respectively).
      Early in the series, one (1.3 %) SILH patient developed bile leak. It was
      successfully managed with 10 days of drainage. No mortality or morbidities
      anastomotic stenosis, cholangitis, pancreatic leak, intestinal obstruction,
      intrahepatic reflux-were encountered. Overall complication rates were identical
      in the two groups (p = 0.32). CONCLUSIONS: SILH is safe in the hands of
      experienced laparoscopic hepaticobiliary surgeons. It achieves comparable
      outcomes with less surgical scar.

PMID- 23539196
TI  - Inherent difficulties of measuring the burden of surgical disease in resource
      poor settings.

PMID- 23539197
TI  - Thromboprophylaxis and VTE rates in soldiers wounded in Operation Enduring
      Freedom and Operation Iraqi Freedom.
AB  - OBJECTIVES: US soldiers suffer catastrophic injuries during combat. We sought to
      define risk factors and rates for VTE in this population. METHODS: We gathered
      data each hospital day on all patients injured in Afghanistan or Iraq who were
      admitted to the Walter Reed Army Medical Center (WRAMC). We analyzed prophylaxis
      rates and efficacy and identified risk factors for VTE. RESULTS: We recorded data
      on 506 combat casualties directly admitted to WRAMC after medical air evacuation.
      The average injury severity score for the group was 18.4 +/- 11.7, and the most
      common reason for air evacuation was injury by improvised explosive device (65%).
      As part of the initial resuscitation, patients received 4.7 +/- 9.0 and 4.00 +/-
      7.8 units of packed RBCs and fresh frozen plasma, respectively, and 42 patients
      received factor VIIa. Forty-six patients (9.1%) were given a diagnosis of VTE
      prior to discharge, 18 (3.6%) during air evacuation, and 28 (5.5%) during the
      hospital stay. In Cox regression analysis, administration of 1 unit of packed
      RBCs was associated with a hazard ratio (HR) of 1.04 (95% CI, 1.02-1.07; P =
      .002), and enoxaparin, 30 mg bid, administered subcutaneously for the majority of
      hospital days was associated with a HR of 0.31 (95% CI, 0.11-0.86; P = .02) for
      VTE during the hospitalization. CONCLUSIONS: Patients who suffer traumatic
      injuries in combat overseas are at high risk for VTE during evacuation and
      recovery. Those with large resuscitations are at particularly high risk, and low
      molecular-weight heparin is associated with a decrease in VTE.

PMID- 23539198
TI  - Transcriptional profiling of Saccharomyces cerevisiae T2 cells upon exposure to
      hardwood spent sulphite liquor: comparison to acetic acid, furfural and
      hydroxymethylfurfural.
AB  - Global gene expression was analyzed in Saccharomyces cerevisiae T2 cells grown in
      the presence of hardwood spent sulphite liquor (HW SSL) and each of the three
      main inhibitors in HW SSL, acetic acid, hydroxymethyfurfural (HMF) and furfural,
      using a S. cerevisiae DNA oligonucleotide microarray. The objective was to
      compare the gene expression profiles of T2 cells in response to the individual
      inhibitors against that elicited in response to HW SSL. Acetic acid mainly
      affected the expression of genes related to the uptake systems of the yeast as
      well as energy generation and metabolism. Furfural and HMF mainly affected the
      transcription of genes involved in the redox balance of the cell. On the other
      hand, the effect of HW SSL on S. cerevisiae T2 cells was distinct and
      considerably more diverse as compared to the effect of individual inhibitors
      found in lignocellulosic hydrolysates. This is not surprising as HW SSL contains
      a complex mixture of inhibitors which may act synergistically. HW SSL elicited
      significant changes in expression of genes involved in diverse and multiple
      effects on several aspects of the cellular structure and function. A notable
      response to HW SSL was decreased expression of the ribosomal protein genes in T2
      cells. In addition, HW SSL decreased the expression of genes functioning in the
      synthesis and transport of proteins as well as metabolism of carbohydrates,
      lipids, vitamins and vacuolar proteins. Furthermore, the expression of genes
      involved in multidrug resistance, iron transport and pheromone response was
      increased, suggesting that T2 cells grown in the presence of HW SSL may have
      activated pheromone response and/or activated pleiotropic drug response. Some of
      the largest changes in gene expression were observed in the presence of HW SSL
      and the affected genes are involved in mating, iron transport, stress response
      and phospholipid metabolism. A total of 59 out of the 400 genes differentially
      expressed in the presence of HW SSL, acetic acid, HMF and furfural, belonged to
      the category of poorly characterized genes. The results indicate that
      transcriptional responses to individual lignocellulosic inhibitors gave a
      different picture and may not be representative of how the cells would respond to
      the presence of all the inhibitors in lignocellulosic hydrolysates such as HW
      SSL.

PMID- 23539199
TI  - Bacterioplankton community structure in the Arctic waters as revealed by
      pyrosequencing of 16S rRNA genes.
AB  - Fjords and open oceans are two typical marine ecosystems in the Arctic region,
      where glacial meltwater and sea ice meltwater have great effects on the
      bacterioplankton community structure during the summer season. This study aimed
      to determine the differences in bacterioplankton communities between these two
      ecosystems in the Arctic region. We conducted a detailed census of microbial
      communities in Kongsfjorden (Spitsbergen) and the Chukchi Borderland using high
      throughput pyrosequencing of the 16S rRNA gene. Gammaproteobacteria and
      Bacteroidetes were the dominant members of the bacterioplankton community in
      Kongsfjorden. By contrast, the most abundant bacterial groups in the surface
      seawater samples from the Chukchi Borderland were Alphaproteobacteria and
      Actinobacteria. Differences in bacterial communities were found between the
      surface and subsurface waters in the investigation area of the Chukchi
      Borderland, and significant differences in bacterial community structure were
      also observed in the subsurface water between the shelf and deep basin areas.
      These results suggest the effect of hydrogeographic conditions on bacterial
      communities. Ubiquitous phylotypes found in all the investigated samples belonged
      to a few bacterial groups that dominate marine bacterioplankton communities. The
      sequence data suggested that changes in environmental conditions result in
      abundant rare phylotypes and reduced amounts of other phylotypes.

PMID- 23539201
TI  - CHILDHOOD TEMPERAMENT-BASED ANTICIPATORY GUIDANCE IN AN HMO SETTING: A
      LONGITUDINAL STUDY.
AB  - This study investigates whether individualized, anticipatory temperament guidance
      could benefit the parent-child relationship and improve children's mental health
      over time. Parents of preschoolers in a health management organization completed
      a temperament questionnaire, received written parenting information tailored to
      their child's temperament, and were asked to complete a program evaluation
      questionnaire. The numbers of subsequent visits to the pediatric and psychiatry
      departments with anxiety, depression, attention deficit hyperactivity disorder,
      and other externalizing behavior diagnoses were compared over 15 years to a
      control sample that received only standard care. Parents positively reviewed the
      program and boys who received the intervention had fewer visits with psychiatric
      diagnoses. Analyses revealed an interaction effect, where boys with harder-to
      manage temperaments saw a greater reduction in visits from the intervention. By
      sensitizing parents to their child's temperament and helping parents understand
      and manage temperament-related behaviors, anticipatory guidance can encourage a
      positive parent-child relationship and reduce future occurrences of psychiatric
      diagnoses.

PMID- 23539200
TI  - Changes in peripheral blood immune cells: their prognostic significance in
      metastatic renal cell carcinoma patients treated with molecular targeted therapy.
AB  - Recently, novel molecular targeted agents markedly changed the treatment of renal
      cell carcinoma (RCC), with promising results. However, there is little
      understanding of how these agents affect immune cell populations in RCC, an
      immunogenic tumor. Therefore, we investigated the changes in the peripheral blood
      immune cells in 58 RCC patients during the first 4 weeks of treatment with
      sorafenib, sunitinib, everolimus, or temsirolimus and evaluated whether these
      changes were associated with clinical outcomes. The immunological parameters were
      the proportion of type-1 (Th1) and type-2 (Th2) T cells, regulatory T cells
      (Treg), mature dendritic cells, and the neutrophil-to-lymphocyte ratio (NLR). The
      changes in these immune cells varied with the agents and the clinical response,
      dichotomized by the median progression-free survival (PFS) time (PFS-short or PFS
      long). A significant decrease in the Th1/Th2 ratio was seen after sunitinib
      treatment only in the PFS-short group, suggesting a shift toward Th2 that down
      regulates host immunity. The NLRs indicative of the balance between host immunity
      and cancer-related inflammation were consistently lower in the PFS-long group
      than in the PFS-short group, suggesting that lower NLR is associated with better
      clinical response. Only sunitinib decreased NLR remarkably regardless of PFS
      status, which may favor anti-tumor immunity. When patients were dichotomized by
      the cutoff values, Th1/Th2 ratio was not associated with PFS in any targeted
      therapy, while lower pre-treatment NLR was associated with longer PFS in each
      targeted therapy. In addition, in RCC patients given sequential targeted therapy,
      those with a lower baseline NLR survived significantly longer compared with the
      counterparts. Moreover, those whose baseline NLR was sustained low during the
      initial therapy survived the longest. Our results suggest the diverse changes in
      host immune cells in RCC patients during targeted therapy. The changes in NLR
      during the early phase of targeted therapy may be a powerful discriminator of who
      will benefit from the subsequent treatment.

PMID- 23539202
TI  - Teratogenic risk perception and confidence in use of medicines in pairs of
      pregnant women and general practitioners based on patient information leaflets.
AB  - OBJECTIVE: The aim of this study was to examine teratogenic risk perceptions and
      confidence in the use of medicines in pairs of pregnant women and general
      practitioners (GPs) through assessments of medicines information texts from
      patient information leaflets (PILs). METHODS: A questionnaire was handed out to
      women attending regular ultrasound examination in week 17-19 of pregnancy. The
      women stated name and address of their GP and questionnaires were sent to the
      GPs' clinic. The questionnaires contained texts regarding pregnancy from PILs for
      pivmecillinam, metoclopramide, paracetamol, escitalopram, Valeriana officinalis
      and dexchlorpheniramine. For each PIL, teratogenic risk (scale from 0: never
      teratogenic to 10: always teratogenic), confidence in use of medicines (yes or
      no) and clarity of the text (scale from 0: exceptionally clear to 3:
      exceptionally unclear) were assessed. RESULTS: In total, 171 pregnant women and
      74 GPs participated, of which 98 pairs were identified. Pregnant women had
      significantly higher perceptions of teratogenic risks and lower confidence in use
      of medicines compared to GPs. Differences in teratogenic risk perceptions and
      confidence in use were highest for escitalopram and lowest for
      dexchlorpheniramine, representing texts with different phrasing and length.
      Neither pregnant women nor GPs were confident in using Valeriana officinalis.
      CONCLUSIONS: Perceptions of teratogenic risks and confidence in use of medicines
      during pregnancy differ within pairs of pregnant women and their GP when they
      assess PILs. Phrasing of medicines information texts can influence teratogenic
      risk perceptions and thereby prescribing of medicines and adherence.

PMID- 23539203
TI  - High cell density fed-batch fermentations for lipase production: feeding
      strategies and oxygen transfer.
AB  - This review is focused on the production of microbial lipases by high cell
      density fermentation. Lipases are among the most widely used of the enzyme
      catalysts. Although lipases are produced by animals and plants, industrial
      lipases are sourced almost exclusively from microorganisms. Many of the
      commercial lipases are produced using recombinant species. Microbial lipases are
      mostly produced by batch and fed-batch fermentation. Lipases are generally
      secreted by the cell into the extracellular environment. Thus, a crude
      preparation of lipases can be obtained by removing the microbial cells from the
      fermentation broth. This crude cell-free broth may be further concentrated and
      used as is, or lipases may be purified from it to various levels. For many large
      volume applications, lipases must be produced at extremely low cost. High cell
      density fermentation is a promising method for low-cost production: it allows a
      high concentration of the biomass and the enzyme to be attained rapidly and this
      eases the downstream recovery of the enzyme. High density fermentation enhances
      enzyme productivity compared with the traditional submerged culture batch
      fermentation. In production of enzymes, a high cell density is generally achieved
      through fed-batch operation, not through perfusion culture which is cumbersome.
      The feeding strategies used in fed-batch fermentations for producing lipases and
      the implications of these strategies are discussed. Most lipase-producing
      microbial fermentations require oxygen. Oxygen transfer in such fermentations is
      discussed. 

PMID- 23539204
TI  - The source ambiguity problem: Distinguishing the effects of grammar and
      processing on acceptability judgments.
AB  - Judgments of linguistic unacceptability may theoretically arise from either
      grammatical deviance or significant processing difficulty. Acceptability data are
      thus naturally ambiguous in theories that explicitly distinguish formal and
      functional constraints. Here, we consider this source ambiguity problem in the
      context of Superiority effects: the dispreference for ordering a wh-phrase in
      front of a syntactically "superior" wh-phrase in multiple wh-questions, e.g. What
      did who buy? More specifically, we consider the acceptability contrast between
      such examples and so-called D-linked examples, e.g. Which toys did which parents
      buy? Evidence from acceptability and self-paced reading experiments demonstrates
      that (i) judgments and processing times for Superiority violations vary in
      parallel, as determined by the kind of wh-phrases they contain, (ii) judgments
      increase with exposure while processing times decrease, (iii) reading times are
      highly predictive of acceptability judgments for the same items, and (iv) the
      effects of the complexity of the wh-phrases combine in both acceptability
      judgments and reading times. This evidence supports the conclusion that D-linking
      effects are likely reducible to independently motivated cognitive mechanisms
      whose effects emerge in a wide range of sentence contexts. This in turn suggests
      that Superiority effects, in general, may owe their character to differential
      processing difficulty.

PMID- 23539205
TI  - Long-term outcomes and prognostic factors for patients with esophageal cancer
      following radiotherapy.
AB  - AIM: To evaluate long-term outcomes and prognostic factors for esophageal
      squamous cell carcinoma (SCC) treated with three dimensional conformal
      radiotherapy (3D-CRT). METHODS: Between January 2005 and December 2006, 153
      patients (120 males, 33 females) with pathologically confirmed esophageal SCC and
      treated with 3D-CRT in Cancer Hospital of Shantou University were included in
      this retrospective analysis. Median age was 60 years (range: 37-84 years). The
      proportion of tumor location was as follows: upper thorax (including the cervical
      region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively.
      The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%)
      received cisplatin-based concurrent chemotherapy. Univariate and multivariate
      analysis were performed to determine the association between the correlative
      factors and prognosis. RESULTS: The five-year overall survival rate was 26.3%,
      with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still
      alive. On univariate analysis, lesion location, lesion length by barium
      esophagogram, computed tomography imaging characteristics including Y diameter
      (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion
      (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume
      (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate
      analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P =
      0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent
      prognostic factors for survival. CONCLUSION: The overall survival of esophageal
      carcinoma patients undergoing 3D-CRT was promising. The best predictors for
      survival were GTV-T and Y diameter.

PMID- 23539206
TI  - Organozinc Chemistry Enabled by Micellar Catalysis. Palladium-Catalyzed Cross
      Couplings between Alkyl and Aryl Bromides in Water at Room Temperature.
AB  - Negishi-like cross-couplings between (functionalized) alkyl and aryl bromides are
      described. Despite the fact that organozinc reagents are intolerant of water,
      their formation as well as their use in an aqueous micellar environment is
      discussed herein. Each component of this complex series of events leading up to C
      C bond formation has an important role which has been determined insofar as the
      type of zinc, amine ligand, surfactant, and palladium catalyst are concerned. In
      particular, the nature of the surfactant has been found to be crucial in order to
      obtain synthetically useful results involving highly reactive, moisture-sensitive
      organometallics. Neither organic solvent nor heat is required for these cross
      couplings to occur; just add water.

PMID- 23539207
TI  - Effects of perfluoroalkyl acids on the function of the thyroid hormone and the
      aryl hydrocarbon receptor.
AB  - Perfluoroalkyl acids (PFAAs) are perfluorinated compounds that widely exist in
      the environment and can elicit adverse effects including endocrine disruption in
      humans and animals. This study investigated the effect of seven PFAAs on the
      thyroid hormone (TH) system assessing the proliferation of the 3,3',5-triiodo-L
      thryonine (T3)-dependent rat pituitary GH3 cells using the T-screen assay and the
      effect on the aryl hydrocarbon receptor (AhR) transactivation in the AhR
      luciferase reporter gene bioassay. A dose-dependent impact on GH3 cells was
      observed in the range 1*10(-9)-1*10(-4) M: seven PFAAs (perfluorooctane sulfonate
      (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid,
      perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic
      acid (PFUnA), and perfluorododecanoic acid (PFDoA)) inhibited the GH3 cell
      growth, and four PFAAs (PFOS, PFHxS, PFNA, and PFUnA) antagonized the T3-induced
      GH3 cell proliferation. At the highest test concentration, PFHxS showed a further
      increase of the T3-induced GH3 growth. Among the seven tested PFAAs, only PFDoA
      and PFDA elicited an activating effect on the AhR. In conclusion, PFAAs possess
      in vitro endocrine-disrupting potential by interfering with TH and AhR functions,
      which need to be taken into consideration when assessing the impact on human
      health.

PMID- 23539208
TI  - Determination of pharmaceuticals, personal care products, and pesticides in
      surface and treated waters: method development and survey.
AB  - Water is fundamental to the existence of life since it is essential to a series
      of activities, such as agriculture, power generation, and public and industrial
      supplies. The residual water generated by these activities is released into the
      environment, reaches the water systems, and becomes a potential risk to nontarget
      organisms. This paper reports the development and validation of a quantitative
      method, based on solid-phase extraction and liquid chromatography tandem mass
      spectrometry, for the simultaneous analysis of 18 pharmaceuticals and personal
      care products (PPCPs) and 33 pesticides in surface and drinking waters. The
      accuracy of the method was determined by calculating the recoveries, which ranged
      from 70 to 120 % for most pesticides and PPCPs, whereas limits of quantification
      ranged from 0.8 to 40 ng/L. After the validation step, the method was applied to
      drinking and surface waters. Pesticides and PPCPs were found in concentrations
      lower than 135.5 ng/L. The evaluation of different water sources with regard to
      contamination by pesticides and PPCPs has been quite poor in southern Brazil.

PMID- 23539209
TI  - Concomitant reduction and immobilization of chromium in relation to its
      bioavailability in soils.
AB  - In this study, two carbon materials [chicken manure biochar (CMB) and black
      carbon (BC)] were investigated for their effects on the reduction of hexavalent
      chromium [Cr(VI)] in two spiked [600 mg Cr(VI) kg(-1)] and one tannery waste
      contaminated [454 mg Cr(VI) kg(-1)] soils. In spiked soils, both the rate and the
      maximum extent of reduction of Cr(VI) to trivalent Cr [Cr(III)] were higher in
      the sandy loam than clay soil, which is attributed to the difference in the
      extent of Cr(VI) adsorption between the soils. The highest rate of Cr(VI)
      reduction was observed in BC-amended sandy loam soil, where it reduced 452 mg kg(
      1) of Cr(VI), followed by clay soil (427 mg kg(-1)) and tannery soil (345 mg kg(
      1)). X-ray photoelectron microscopy confirmed the presence of both Cr(VI) and
      Cr(III) species in BC within 24 h of addition of Cr(VI), which proved its high
      reduction capacity. The resultant Cr(III) species either adsorbs or precipitates
      in BC and CMB. The addition of carbon materials to the tannery soil was also
      effective in decreasing the phytotoxicity of Cr(VI) in mustard (Brassica juncea
      L.) plants. Therefore, it is concluded that the addition of carbon materials
      enhanced the reduction of Cr(VI) and the subsequent immobilization of Cr(III) in
      soils.

PMID- 23539210
TI  - RNAi-mediated abrogation of trehalase expression does not affect trehalase
      activity in sugarcane.
AB  - To engineer trehalose metabolism in sugarcane (Saccharum spp. hybrids) two
      transgenes were introduced to the genome: trehalose-6-phosphate synthase-
      phosphatase (TPSP), to increase trehalose biosynthesis and an RNAi transgene
      specific for trehalase, to abrogate trehalose catabolism. In RNAi-expressing
      lines trehalase expression was abrogated in many plants however no decrease in
      trehalase activity was observed. In TPSP lines trehalase activity was
      significantly higher. No events of co-integration of TPSP and RNAi transgenes
      were observed. We suggest trehalase activity is essential to mitigate embryonic
      lethal effects of trehalose metabolism and discuss the implications for
      engineering trehalose metabolism. 

PMID- 23539211
TI  - The nasal keystone region: an anatomical study.

PMID- 23539212
TI  - Assessment of bone channels other than the nasopalatine canal in the anterior
      maxilla using limited cone beam computed tomography.
AB  - PURPOSE: The anterior maxilla, sometimes also called premaxilla, is an area
      frequently requiring surgical interventions. The objective of this observational
      study was to identify and assess accessory bone channels other than the
      nasopalatine canal in the anterior maxilla using limited cone beam computed
      tomography (CBCT). METHODS: A total of 176 cases fulfilled the inclusion criteria
      comprising region of interest, quality of CBCT image, and absence of pathologic
      lesions or retained teeth. Any bone canal with a minimum diameter of 1.00 mm
      other than the nasopalatine canal was analyzed regarding size, location, and
      course, as well as patient gender and age. RESULTS: A total of 67 accessory
      canals >=1.00 mm were found in 49 patients (27.8%). A higher frequency of
      accessory canals was observed in males (33.0%) than in females (22.7%) (p =
      0.130). Accessory canals occurred more frequently in older rather than younger
      patients (p = 0.115). The mean diameter of accessory canals was 1.31 +/- 0.26 mm
      (range 1.01-2.13 mm). Gender and age did not significantly influence the
      diameter. Accessory canals were found palatal to all anterior teeth, but most
      frequently palatal to the central incisors. In 56.7%, the accessory canals curved
      superolaterally and communicated with the ipsilateral alveolar extension of the
      canalis sinuosus. CONCLUSIONS: The study confirms the presence of bone channels
      within the anterior maxilla other than the nasopalatine canal. More than half of
      these accessory bone canals communicated with the canalis sinuosus. From a
      clinical perspective, studies are needed to determine the content of these
      accessory canals.

PMID- 23539213
TI  - A systems biology framework identifies molecular underpinnings of coronary heart
      disease.
AB  - OBJECTIVE: Genetic approaches have identified numerous loci associated with
      coronary heart disease (CHD). The molecular mechanisms underlying CHD gene
      disease associations, however, remain unclear. We hypothesized that genetic
      variants with both strong and subtle effects drive gene subnetworks that in turn
      affect CHD. APPROACH AND RESULTS: We surveyed CHD-associated molecular
      interactions by constructing coexpression networks using whole blood gene
      expression profiles from 188 CHD cases and 188 age- and sex-matched controls.
      Twenty-four coexpression modules were identified, including 1 case-specific and 1
      control-specific differential module (DM). The DMs were enriched for genes
      involved in B-cell activation, immune response, and ion transport. By integrating
      the DMs with gene expression-associated single-nucleotide polymorphisms and with
      results of genome-wide association studies of CHD and its risk factors, the
      control-specific DM was implicated as CHD causal based on its significant
      enrichment for both CHD and lipid expression-associated single-nucleotide
      polymorphisms. This causal DM was further integrated with tissue-specific
      Bayesian networks and protein-protein interaction networks to identify regulatory
      key driver genes. Multitissue key drivers (SPIB and TNFRSF13C) and tissue
      specific key drivers (eg, EBF1) were identified. CONCLUSIONS: Our network-driven
      integrative analysis not only identified CHD-related genes, but also defined
      network structure that sheds light on the molecular interactions of genes
      associated with CHD risk.

PMID- 23539214
TI  - Application of infrared laser to the zebrafish vascular system: gene induction,
      tracing, and ablation of single endothelial cells.
AB  - OBJECTIVE: Infrared laser-evoked gene operator is a new microscopic method
      optimized to heat cells in living organisms without causing photochemical damage.
      By combining the promoter system for the heat shock response, infrared laser
      evoked gene operator enables laser-mediated gene induction in targeted cells. We
      applied this method to the vascular system in zebrafish embryos and demonstrated
      its usability to investigate mechanisms of vascular morphogenesis in vivo.
      APPROACH AND RESULTS: We used double-transgenic zebrafish with fli1:nEGFP to
      identify the endothelial cells, and with hsp:mCherry to carry out single-cell
      labeling. Optimizing the irradiation conditions, we finally succeeded in inducing
      the expression of the mCherry gene in single targeted endothelial cells, at a
      maximum efficiency rate of 60%. In addition, we indicated that this system could
      be used for laser ablation under certain conditions. To evaluate infrared laser
      evoked gene operator, we applied this system to the endothelial cells of the
      first intersegmental arteries, and captured images of the connection between the
      vascular systems of the brain and spinal cord. CONCLUSIONS: Our results suggest
      that the infrared laser-evoked gene operator system will contribute to the
      elucidation of the mechanisms underlying vascular morphogenesis by controlling
      spatiotemporal gene activation in single endothelial cells, by labeling or
      deleting individual vessels in living embryos.

PMID- 23539215
TI  - Essential role of SH3-domain GRB2-like 3 for vascular lumen maintenance in
      zebrafish.
AB  - OBJECTIVE: Studying the underlying molecular mechanisms for maintaining
      stereotyped vascular lumen diameters should help toward a comprehensive
      understanding of vascular homeostasis and function. We aimed to determine the
      role of SH3-domain GRB2-like 3 (Sh3gl3) and its interacting pathways in dorsal
      aorta (DA) maintenance in zebrafish. APPROACH AND RESULTS: Sh3gl3 and its binding
      partner, Cbl-interacting protein of 85K (Cin85), together regulate endocytosis
      and were expressed in the developing vasculature. Morpholino knockdown of either
      gene resulted in shrinkage of the DA lumen, although artery/vein specification
      and the initial formation of vascular lumens were unaffected. In addition, sh3gl3
      and cin85 morpholinos exerted a synergistic effect in causing the vascular
      phenotypes. To identify the signaling pathways in which Sh3gl3/Cin85 may
      participate, we screened several candidate inhibitors for their ability to induce
      similar circulatory defects. Chemical inhibition of the epidermal growth factor
      receptor and the phosphatidylinositol 3-kinase/Akt cascade led to a loss of
      circulation and shrunken DA in zebrafish embryos. Furthermore, inhibition of the
      epidermal growth factor receptor/phosphatidylinositol 3-kinase pathway showed a
      functional cooperation with Sh3gl3 deficiency in impairing DA lumens.
      CONCLUSIONS: These results identify 2 new factors, Sh3gl3 and Cin85, which are
      essential for DA lumen maintenance, and suggest that endocytosis, possibly
      involving epidermal growth factor receptor and phosphatidylinositol 3-kinase, is
      implicated in Sh3gl3/Cin85 function.

PMID- 23539216
TI  - Tissue characterization after drug-eluting stent implantation using optical
      coherence tomography.
AB  - OBJECTIVE: To validate optical coherence tomography (OCT) imaging for assessment
      of vascular healing in a preclinical animal model and human autopsy cases and to
      translate the findings to the assessment of vascular healing after drug-eluting
      stent implantation in clinical practice. APPROACH AND RESULTS: Drug-eluting and
      bare metal stents were imaged 28 and 42 days after implantation in
      atherosclerotic rabbits using OCT and simultaneously evaluated by histology.
      After coregistration with histology, gray-scale signal intensity (GSI) was
      measured for identified mature or immature neointimal tissue. Autopsy specimens
      were imaged with OCT and GSI values correlated with histology. Finally,
      prospective OCT imaging and GSI measurements were acquired in 10 patients
      undergoing follow-up 6 months after stenting with drug-eluting stents.
      Histopathologic and OCT morphometric analysis of implanted stents showed
      excellent correlation. Neointimal growth and vessel healing at 28 days in the
      animal model best correlated with human stented arteries at 6 months. In animal
      and human autopsy specimens, mature neointimal tissue consistently showed higher
      GSI values. Receiver operating characteristic curve analysis displayed high
      sensitivity and specificity for detection of mature neointima in animal (96% and
      79%, respectively) and human autopsy (89% and 71%, respectively) data. In
      patients undergoing OCT follow-up 6 months after drug-eluting stent implantation,
      prospective GSI analysis revealed that a minimum of 27.7% of areas above stent
      struts represented mature neointima. CONCLUSIONS: Novel GSI analysis of OCT
      imaging data allows distinction between mature and immature neointimal tissue in
      animal models, autopsy specimens, and patients undergoing invasive surveillance
      in simple atherosclerotic lesions.

PMID- 23539217
TI  - Liver kinase B1 is required for thromboxane receptor-dependent nuclear factor
      kappaB activation and inflammatory responses.
AB  - OBJECTIVE: Thromboxane A2 receptor (TPr) has been reported to trigger vascular
      inflammation. Nuclear factor kappa B (NF-kappaB) is a known transcription factor.
      The aims of the present study were to determine the contributions of NF-kappaB
      activation to TPr-triggered vascular inflammation and elucidate the mechanism(s)
      underlying TPr activation of NF-kappaB. APPROACH AND RESULTS: The effects of TPr
      activators, [1S-[1 alpha,2 alpha(Z),3beta(1E,3S*), 4 alpha]]-7-[3-[3-hydroxy-4-(4
      iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP)
      and U46619, on NF-kappaB activation, phosphorylation of rhoA/rho-associated
      kinases and liver kinase B1, cell adhesion and migration, proliferation, and
      endothelium-dependent vasorelaxation were assayed in cultured human umbilical
      vein endothelial cells, human monocytes, or isolated mouse aortas. Exposure of
      human umbilical vein endothelial cells to TPr agonists I-BOP and U46619 induced
      dose-dependent and time-dependent phosphorylation of inhibitor of kappaB alpha in
      parallel with aberrant expression of inflammatory markers cyclooxygenase-2,
      inducible nitric oxide synthase, intercellular adhesion molecule-1, and vascular
      cell adhesion molecule-1. Inhibition of NF-kappaB by pharmacological or genetic
      means abolished TPr-triggered expression of inflammatory markers. Consistently,
      exposure of human umbilical vein endothelial cells to either I-BOP or U46619
      significantly increased phosphorylation of inhibitor of kappaB alpha, I kappaB
      kinase, rhoA, rho-associated kinases, and liver kinase B1. Pretreatment of human
      umbilical vein endothelial cells with the TPr antagonist SQ29548 or rho
      associated kinases inhibitor Y27632 or silencing of the LKB1 blocked TPr-enhanced
      phosphorylation of inhibitor of kappaB alpha and its upstream kinase, I kappaB
      kinase. Finally, exposure of isolated mouse aortas to either U46619 or I-BOP
      enhanced NF-kappaB activation and vascular inflammation in parallel with reduced
      endothelium-dependent relaxation in intact vessels. CONCLUSIONS: TPr stimulation
      instigates aberrant inflammation and endothelial dysfunction via rho-associated
      kinases/liver kinase B1/I kappaB kinase-dependent NF-kappaB activation in
      vascular endothelial cells.

PMID- 23539218
TI  - Gene expression signatures of coronary heart disease.
AB  - OBJECTIVE: To identify transcriptomic biomarkers of coronary heart disease (CHD)
      in 188 cases with CHD and 188 age- and sex-matched controls who were participants
      in the Framingham Heart Study. APPROACH AND RESULTS: A total of 35 genes were
      differentially expressed in cases with CHD versus controls at false discovery
      rate<0.5, including GZMB, TMEM56, and GUK1. Cluster analysis revealed 3 gene
      clusters associated with CHD, 2 linked to increased erythrocyte production and a
      third to reduced natural killer and T cell activity in cases with CHD. Exon-level
      results corroborated and extended the gene-level results. Alternative splicing
      analysis suggested that GUK1 and 38 other genes were differentially spliced in
      cases with CHD versus controls. Gene Ontology analysis linked ubiquitination and
      T-cell-related pathways with CHD. CONCLUSIONS: Two bioinformatically defined
      groups of genes show consistent associations with CHD. Our findings are
      consistent with the hypotheses that hematopoesis is upregulated in CHD, possibly
      reflecting a compensatory mechanism, and that innate immune activity is disrupted
      in CHD or altered by its treatment. Transcriptomic signatures may be useful in
      identifying pathways associated with CHD and point toward novel therapeutic
      targets for its treatment and prevention.

PMID- 23539219
TI  - Nectin-like molecule-5 regulates intimal thickening after carotid artery ligation
      in mice.
AB  - OBJECTIVE: Intimal thickening is considered to result from the dedifferentiation
      of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype,
      and their subsequent migration and proliferation. It is unknown whether nectin
      like molecule (Necl)-5, which is overexpressed in cancer cells, is involved in
      intimal thickening. APPROACH AND RESULTS: Necl-5 was upregulated in mouse carotid
      artery after ligation. Compared with wild-type mice, intimal thickening after
      carotid artery ligation was milder in Necl-5 knockout mice. In vitro, the
      expression levels of SMC differentiation markers were higher, whereas the
      expression level of an SMC dedifferentiation marker was lower, in Necl-5 knockout
      mouse aortic SMCs (MASMCs) compared with wild-type MASMCs. The migration,
      proliferation, and extracellular signal-regulated kinase activity in response to
      serum were decreased in Necl-5 knockout MASMCs compared with wild-type MASMCs. In
      wild-type MASMCs, inhibition of extracellular signal-regulated kinase activity
      increased the expression levels of SMC differentiation markers and decreased
      their migration and proliferation in response to serum. CONCLUSIONS: The present
      findings indicate that Necl-5 plays a role in the formation of intimal thickening
      after carotid artery ligation by regulating dedifferentiation, migration, and
      proliferation of SMCs in an extracellular signal-regulated kinase-dependent
      manner. Our results suggest that Necl-5 may represent a potential therapeutic
      target to limit intimal thickening after vascular injury.

PMID- 23539220
TI  - Photodynamic therapy using a protease-mediated theranostic agent reduces
      cathepsin-B activity in mouse atheromata in vivo.
AB  - OBJECTIVE: To investigate whether an intravenously injected cathepsin-B
      activatable theranostic agent (L-SR15) would be cleaved in and release a
      fluorescent agent (chlorin-e6) in mouse atheromata, allowing both the diagnostic
      visualization and therapeutic application of these fluorophores as
      photosensitizers during photodynamic therapy to attenuate plaque-destabilizing
      cathepsin-B activity by selectively eliminating macrophages. APPROACH AND
      RESULTS: Thirty-week-old apolipoprotein E knock-out mice (n=15) received
      intravenous injection of L-SR15 theranostic agent, control agent D-SR16, or
      saline 3* (D0, D7, D14). Twenty-four hours after each injection, the bilateral
      carotid arteries were exposed, and Cy5.5 near-infrared fluorescent imaging was
      performed. Fluorescent signal progressively accumulated in the atheromata of the
      L-SR15 group animals only, indicating that photosensitizers had been released
      from the theranostic agent and were accumulating in the plaque. After each
      imaging session, photodynamic therapy was applied with a continuous-wave diode
      laser. Additional near-infrared fluorescent imaging at a longer wavelength (Cy7)
      with a cathepsin-B-sensing activatable molecular imaging agent showed attenuation
      of cathepsin-B-related signal in the L-SR15 group. Histological studies
      demonstrated that L-SR15-based photodynamic therapy decreased macrophage
      infiltration by inducing apoptosis without significantly affecting plaque size or
      smooth muscle cell numbers. Toxicity studies (n=24) showed that marked
      erythematous skin lesion was generated in C57/BL6 mice at 24 hours after
      intravenous injection of free chlorin-e6 and ultraviolet light irradiation;
      however, L-SR15 or saline did not cause cutaneous phototoxicity beyond that
      expected of ultraviolet irradiation alone, neither did we observe systemic
      toxicity or neurobehavioral changes. CONCLUSIONS: This is the first study showing
      that macrophage-secreted cathepsin-B activity in atheromata could be attenuated
      by photodynamic therapy using a protease-mediated theranostic agent.

PMID- 23539223
TI  - Latino parental help seeking for childhood ADHD.
AB  - To better understand the help seeking process that occurs within Latino families
      when a child is exhibiting behaviors consistent with attention
      deficit/hyperactivity disorder (ADHD), qualitative and quantitative data from 73
      Latino parents were examined. Findings suggest that most Latino parents in the
      current sample recognized ADHD symptoms as concerning and in need of professional
      help and reported being motivated to seek help. Unfortunately, they also appeared
      to lack knowledge about the etiology of and effective treatment for ADHD, and
      many identified barriers to seeking help. Future research must involve community
      collaborations aimed at increasing awareness and knowledge of ADHD and decreasing
      barriers to seeking help in targeted Latino communities.

PMID- 23539221
TI  - Cocaine and specific cocaine metabolites induce von Willebrand factor release
      from endothelial cells in a tissue-specific manner.
AB  - OBJECTIVE: Cocaine use is associated with arterial thrombosis, including
      myocardial infarction and stroke. Cocaine use results in increased plasma von
      Willebrand factor (VWF), accelerated atherosclerosis, and platelet-rich arterial
      thrombi, suggesting that cocaine activates the endothelium, promoting platelet
      VWF interactions. APPROACH AND RESULTS: Human umbilical vein endothelial cells,
      brain microvasculature endothelial cells, or coronary artery endothelial cells
      were treated with cocaine or metabolites benzoylecgonine, cocaethylene,
      norcocaine, or ecgonine methylester. Supernatant VWF concentration and multimer
      structure were measured, and platelet-VWF strings formed on the endothelial
      surface under flow were quantified. Cocaine, benzoylecgonine, and cocaethylene
      induced endothelial VWF release, with the 2 metabolites being more potent than
      the parent molecule. Brain microvasculature endothelial cells were more sensitive
      to cocaine and metabolites than were human umbilical vein endothelial cells or
      coronary artery endothelial cells. Coronary artery endothelial cells released VWF
      into the supernatant but did not form VWF-platelet strings. Intracellular cAMP
      concentration was not increased after treatment with cocaine or its metabolites.
      CONCLUSIONS: Both cocaine and metabolites benzoylecgonine and cocaethylene
      induced endothelial VWF secretion, possibly explaining thrombotic risk after
      cocaine ingestion. VWF secretion is likely to vary between vascular beds, with
      brain endothelial cells being particularly sensitive. These results suggest that
      clinical management of cocaine-induced ischemia may benefit from therapies aimed
      at disrupting the VWF-platelet interaction.

PMID- 23539224
TI  - Nutrition as medical therapy in pediatric critical illness.

PMID- 23539225
TI  - Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes.
AB  - BACKGROUND AND OBJECTIVES: Congenital anomalies of the kidney and urinary tract
      (CAKUT) are a frequent cause of renal failure in children, and their detection in
      utero is now common with fetal screening ultrasonography. The clinical course of
      CAKUT detected before birth is very heterogeneous and depends on the level of
      nephron reduction. The most severe forms cause life-threatening renal failure,
      leading to perinatal death or the need for very early renal replacement therapy.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study reports the screening
      of two genes (HNF1B and PAX2) involved in monogenic syndromic CAKUT in a cohort
      of 103 fetuses from 91 families with very severe CAKUT that appeared isolated by
      fetal ultrasound examination and led to termination of pregnancy. RESULTS: This
      study identified a disease-causing mutation in HNF1B in 12 cases from 11 families
      and a mutation in PAX2 in 4 unrelated cases. Various renal phenotypes were
      observed, but no case of bilateral agenesis was associated with HNF1B or PAX2
      mutations. Autopsy identified extrarenal abnormalities not detected by
      ultrasonography in eight cases but confirmed the absence of extrarenal defects in
      eight other cases. A positive family history of renal disease was not
      significantly more frequent in cases with an identified mutation. Moreover, in
      cases with an inherited mutation, there was a great phenotypic variability
      regarding the severity of the renal disease within a single family. CONCLUSIONS:
      Our results suggest that mutations in genes involved in syndromic CAKUT with
      Mendelian inheritance are not rare in fetal cases with severe CAKUT appearing
      isolated at prenatal ultrasound, a finding of clinical importance because of
      genetic counseling.

PMID- 23539226
TI  - American Society of Nephrology Quiz and Questionnaire 2012: glomerulonephritis.
AB  - Presentation of the Nephrology Quiz and Questionnaire (NQQ) has become an annual
      tradition at the meetings of the American Society of Nephrology. It is a very
      popular session, judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time, using
      audience response devices, to those of program directors of nephrology training
      programs in the United States, acquired through an Internet-based questionnaire.
      The topic presented here is GN. Cases representing this category, along with
      single best answer questions, were prepared by a panel of experts (Drs. Fervenza,
      Glassock, and Bleyer). The correct and incorrect answers were then briefly
      discussed after the audience responses and the results of the questionnaire were
      displayed. This article recapitulates the session and reproduces its educational
      value for a larger audience--that of the readers of the Clinical Journal of the
      American Society of Nephrology. Have fun.

PMID- 23539227
TI  - The relationship of age, race, and ethnicity with survival in dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Reports on the racial and ethnic differences in
      dialysis patient survival rates have been inconsistent. The literature suggests
      that these survival differences may be modified by age as well as categorizing
      white race as inclusive of Hispanic ethnicity. The goal of this study was to
      better understand these associations by examining survival among US dialysis
      patients by age, ethnicity, and race. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Between 1995 and 2009, 1,282,201 incident dialysis patients ages 18
      years or older were identified in the United States Renal Data System. Dialysis
      survival was compared among non-Hispanic blacks, non-Hispanic whites, and
      Hispanics overall and stratified by seven age groups. RESULTS: The median
      duration of follow-up was 22.3 months. Compared with non-Hispanic whites, a lower
      mortality risk was seen in Hispanics in all age groups. Consequently, when
      Hispanic patients were excluded from the white race, the mortality rates in white
      race all increased. Using non-Hispanic whites as the reference, a significantly
      lower mortality risk for non-Hispanic blacks was consistently observed in all age
      groups above 30 years (unadjusted hazard ratios ranged from 0.70 to 0.87; all
      P<0.001). In the 18- to 30-years age group, there remained an increased mortality
      risk in blacks versus non-Hispanic whites after adjustment for case mix (adjusted
      hazard ratio=1.19, 95% confidence interval=1.13-1.25). CONCLUSIONS: The mortality
      risk was lowest in Hispanics, intermediate in non-Hispanic blacks, and highest in
      non-Hispanic whites. This pattern generally holds in all age groups except for
      the 18- to 30-years group, where the adjusted mortality rate for non-Hispanic
      blacks exceeds the adjusted mortality rate of non-Hispanic whites.

PMID- 23539229
TI  - Toward population management in an integrated care model.
AB  - Under the Patient Protection and Affordable Care Act of 2010, accountable care
      organizations (ACOs) will be the primary mechanism for achieving the dual goals
      of high-quality patient care at managed per capita costs. To achieve these goals
      in the newly emerging health care environment, the nephrology community must plan
      for and direct integrated delivery and coordination of renal care, focusing on
      population management. Even though the ESRD patient population is a complex group
      with comorbid conditions that may confound integration of care, the nephrology
      community has unique experience providing integrated care through ACO-like
      programs. Specifically, the recent ESRD Management Demonstration Project
      sponsored by the Centers for Medicare & Medicaid Services and the current ESRD
      Prospective Payment System with it Quality Incentive Program have demonstrated
      that integrated delivery of renal care can be accomplished in a manner that
      provides improved clinical outcomes with some financial margin of savings. Moving
      forward, integrated renal care will probably be linked to provider performance
      and quality outcomes measures, and clinical integration initiatives will share
      several common elements, namely performance-based payment models, coordination of
      communication via health care information technology, and development of best
      practices for care coordination and resource utilization. Integration initiatives
      must be designed to be measured and evaluated, and, consistent with principles of
      continuous quality improvement, each initiative will provide for iterative
      improvements of the initiative.

PMID- 23539228
TI  - Adverse drug events during AKI and its recovery.
AB  - BACKGROUND AND OBJECTIVES: The impact of AKI on adverse drug events and
      therapeutic failures and the medication errors leading to these events have not
      been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A single
      center observational study of 396 hospitalized patients with a minimum 0.5 mg/dl
      change in serum creatinine who were prescribed a nephrotoxic or renally
      eliminated medication was conducted. The population was stratified into two
      groups by the direction of their initial serum creatinine change: AKI and AKI
      recovery. Adverse drug events, potential adverse drug events, therapeutic
      failures, and potential therapeutic failures for 148 drugs and 46 outcomes were
      retrospectively measured. Events were classified for preventability and severity
      by expert adjudication. Multivariable analysis identified medication classes
      predisposing AKI patients to adverse drug events. RESULTS: Forty-three percent of
      patients experienced a potential adverse drug event, adverse drug event,
      therapeutic failure, or potential therapeutic failure; 66% of study events were
      preventable. Failure to adjust for kidney function (63%) and use of nephrotoxic
      medications during AKI (28%) were the most common potential adverse drug events.
      Worsening AKI and hypotension were the most common preventable adverse drug
      events. Most adverse drug events were considered serious (63%) or life
      threatening (31%), with one fatal adverse drug event. Among AKI patients,
      administration of angiotensin-converting enzyme inhibitors/angiotensin receptor
      blockers, antibiotics, and antithrombotics was most strongly associated with the
      development of an adverse drug event or potential adverse drug event.
      CONCLUSIONS: Adverse drug events and potential therapeutic failures are common
      and frequently severe in patients with AKI exposed to nephrotoxic or renally
      eliminated medications.

PMID- 23539230
TI  - American Society of Nephrology Quiz and Questionnaire 2012: Transplantation.
AB  - Presentation of the Nephrology Quiz and Questionnaire has become an annual
      tradition at the meetings of the American Society of Nephrology. It is a very
      popular session, as judged by consistently large attendance. Members of the
      audience test their knowledge and judgment on a series of case-oriented questions
      prepared and discussed by experts. They can also compare their answers in real
      time, using audience response devices, to those of program directors of
      nephrology training programs in the United States, acquired through an Internet
      based questionnaire. Topics presented here include fluid and electrolyte
      disorders, transplantation, and ESRD and dialysis. Cases representing each of
      these categories, along with single-best-answer questions, were prepared by a
      panel of experts (Drs. Palmer, Fervenza, Brennan, and Mehrotra, respectively).
      The correct and incorrect answers were briefly discussed after the audience
      responses, and the results of the questionnaire were displayed. This article
      recapitulates the session and reproduces its educational value for a larger
      audience--that of the readers of the Clinical Journal of the American Society of
      Nephrology. Have fun.

PMID- 23539231
TI  - 24-hour urine phosphorus excretion and mortality and cardiovascular events.
AB  - BACKGROUND AND OBJECTIVES: Higher morning serum phosphorus has been associated
      with cardiovascular disease (CVD) in patients with or without CKD. In patients
      with CKD and a phosphorous level >4.6 mg/dl, the Kidney Disease Improving Global
      Outcomes guidelines recommend dietary phosphorus restriction. However, whether
      phosphorus restriction influences serum phosphorus concentrations and whether
      dietary phosphorus is itself associated with CVD or death are uncertain. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Among 880 patients with stable CVD and
      normal kidney function to moderate CKD, 24-hour urine phosphorus excretion (UPE)
      and serum phosphorus were measured at baseline. Participants were followed for a
      median of 7.4 years for CVD events and all-cause mortality. RESULTS: Mean +/- SD
      age was 67+/-11 years, estimated GFR (eGFR) was 71+/-22 ml/min per 1.73 m(2), and
      serum phosphorus was 3.7+/-0.6 mg/dl. Median UPE was 632 (interquartile range,
      439, 853) mg/d. In models adjusted for demographic characteristics and eGFR, UPE
      was weakly and nonsignificantly associated with serum phosphorus (0.03 mg/dl
      higher phosphorus per 300 mg higher UPE; P=0.07). When adjusted for demographics,
      eGFR, and CVD risk factors, each 300-mg higher UPE was associated with 17% lower
      risk of CVD events. The association of UPE with all-cause mortality was not
      statistically significant (hazard ratio, 0.93; 95% confidence interval, 0.82 to
      1.05). Results were similar irrespective of CKD status (P interactions > 0.87).
      CONCLUSIONS: Among outpatients with stable CVD, the magnitude of the association
      of UPE with morning serum phosphorus is modest. Greater UPE is associated with
      lower risk for CVD events. The association was similar for all-cause mortality
      but was not statistically significant.

PMID- 23539232
TI  - Glomerular and tubular damage markers in individuals with progressive
      albuminuria.
AB  - BACKGROUND AND OBJECTIVES: Albuminuria is associated with risk for renal and
      cardiovascular disease. It is difficult to predict which persons will progress in
      albuminuria. This study investigated whether assessment of urinary markers
      associated with damage to different parts of the nephron may help identify
      individuals that will progress in albuminuria. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Individuals were selected from a prospective community-based cohort
      study with serial follow-up and defined as "progressors" if they belonged to the
      quintile of participants with the most rapid annual increase in albuminuria, and
      reached an albuminuria >=150 mg/d during follow-up. Patients with known renal
      disease or macroalbuminuria at baseline were excluded. Each progressor was
      matched to two control participants, based on baseline albuminuria, age, and sex.
      Furthermore, damage markers were measured in a separate set of healthy
      individuals. RESULTS: After a median follow-up of 8.6 years, 183 of 8394
      participants met the criteria for progressive albuminuria. Baseline clinical
      characteristics were comparable between progressors and matched controls (n=366).
      Both had higher baseline albuminuria than the overall population. Urinary
      excretion of the glomerular damage marker IgG was significantly higher in
      progressors, whereas urinary excretion of proximal tubular damage markers and
      inflammatory markers was lower in these individuals compared with controls.
      Healthy individuals (n=109) had the lowest values for all urinary damage markers
      measured. CONCLUSIONS: These data suggest that albuminuria associated with
      markers of glomerular damage is more likely to progress, whereas albuminuria
      associated with markers of tubulointerstitial damage is more likely to remain
      stable.

PMID- 23539233
TI  - Efficacy and safety of insulin glargine compared to other interventions in
      younger and older adults: a pooled analysis of nine open-label, randomized
      controlled trials in patients with type 2 diabetes.
AB  - OBJECTIVE: Elderly patients with type 2 diabetes mellitus (T2DM) present
      therapeutic challenges related to co-morbidities, treatment adherence, and
      safety. This study examines the efficacy and safety of insulin glargine compared
      to other glucose-lowering interventions in younger and older adults. METHODS: In
      this pooled analysis of 24-week data from nine prospective open-label,
      multicenter, phase 3/4, two-arm, parallel-group, randomized controlled trials,
      patients with T2DM aged 18-80 years received insulin glargine (used as a basal
      insulin regimen) or comparators (including rosiglitazone, pioglitazone, insulin
      lispro, insulin lispro 75/25, NPH insulin, NPH insulin 30/70, and
      lifestyle/dietary measures). Endpoints included change from baseline to week 24
      in: glycated hemoglobin; fasting plasma glucose; body weight; body mass index;
      insulin dose; incidence of nocturnal, daytime, or any hypoglycemia. Results were
      stratified by age (<65, >=65, 65-74, and >=75 years) and treatment (insulin
      glargine or comparator). RESULTS: A total of 2,938 patients were included (2,263
      aged <65 years, 675 aged >=65 years). Similar levels of glycemic control were
      achieved in both younger (<65 years) and older (>=65 years) patients with T2DM.
      Insulin glargine was associated with better glycemic control and a reduced
      incidence of daytime and any hypoglycemia versus comparator interventions in both
      younger and older T2DM patients. CONCLUSION: This analysis suggests that insulin
      glargine may represent a safe option to improve glycemic control in older
      patients with T2DM.

PMID- 23539235
TI  - Monitoring depth of anaesthesia in a randomized trial decreases the rate of
      postoperative delirium but not postoperative cognitive dysfunction.
AB  - BACKGROUND: Postoperative delirium in elderly patients is a frequent complication
      and associated with poor outcome. The aim of this parallel group study was to
      determine whether monitoring depth of anaesthesia influences the incidence of
      postoperative delirium. METHODS: Patients who were planned for surgery in general
      anaesthesia expected to last at least 60 min and who were older than 60 yr were
      included between March 2009 and May 2010. A total of 1277 patients of a
      consecutive sample were randomized (n=638 open, n=639 blinded) and the data of
      1155 patients were analysed (n=575 open, n=580 blinded). In one group, the
      anaesthesiologists were allowed to use the bispectral index (BIS) data to guide
      anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive
      function was evaluated at baseline, 1 week, and 3 months after operation.
      RESULTS: Delirium incidence was lower in patients guided with BIS. Postoperative
      delirium was detected in 95 patients (16.7%) in the intervention group compared
      with 124 patients (21.4%) in the control group (P=0.036). In a multivariate
      analysis, the percentage of episodes of deep anaesthesia (BIS values <20) were
      independently predictive for postoperative delirium (P=0.006; odds ratio 1.027).
      BIS monitoring did not alter the incidence of postoperative cognitive dysfunction
      (7th day P=0.062; 90th day P=0.372). CONCLUSIONS: Intraoperative neuromonitoring
      is associated with a lower incidence of delirium, possibly by reducing extreme
      low BIS values. Therefore, in high-risk surgical patients, this may give the
      anaesthesiologist a possibility to influence one precipitating factor in the
      complex genesis of delirium. Clinical trial registration ISRCTN Register:
      36437985. http://www.controlled-trials.com/ISRCTN36437985/.

PMID- 23539234
TI  - Ranibizumab: a review of its use in the treatment of neovascular age-related
      macular degeneration.
AB  - Ranibizumab (Lucentis((r))), an inhibitor of all vascular endothelial growth
      factor (VEGF) A isoforms, is approved for the intravitreal treatment of
      neovascular age-related macular degeneration (AMD). In pivotal trials, monthly
      injections of ranibizumab were superior to verteporfin photodynamic therapy in
      the treatment of predominantly classic choroidal neovascularization (CNV) due to
      neovascular AMD (ANCHOR) and sham in the treatment of minimally classic or occult
      CNV due to neovascular AMD (MARINA). Monthly or less frequent injections of
      ranibizumab are generally well tolerated and associated with low rates of ocular
      and systemic serious adverse events (SAEs). Less frequent dosing has been
      evaluated with the aim of reducing the burden, risk and cost of monthly
      injections. In the landmark CATT trial, monthly monitoring and retreatment as
      needed with ranibizumab was equivalent to monthly treatment in terms of the
      vision gain at 1 year, but reduced the number of injections (and the related
      cost) by approximately one-half. In head-to-head comparisons, aflibercept
      administered bimonthly was noninferior to ranibizumab administered monthly (VIEW
      1 and 2), bevacizumab administered monthly was equivalent to ranibizumab
      administered monthly (CATT), and bevacizumab administered as-needed was
      equivalent to ranibizumab administered as-needed (CATT). Bevacizumab is widely
      used (off-label) for economic reasons; while it was less costly than ranibizumab,
      it was associated with more systemic SAEs. Notwithstanding the availability of
      other similarly effective anti-VEGF therapies that are approved (aflibercept) or
      unapproved (bevacizumab), ranibizumab continues to set the standard as regards
      the totality of evidence from randomized clinical trials demonstrating its
      efficacy and tolerability (particularly that of the monthly regimen) in the
      treatment of neovascular AMD.

PMID- 23539237
TI  - SENSITIVITY OF PASSIVE APPROACH DURING PREFERENCE AND REINFORCER ASSESSMENTS FOR
      CHILDREN WITH SEVERE AND PROFOUND INTELLECTUAL DISABILITIES AND MINIMAL MOVEMENT.
AB  - We evaluated the use of passive approach to assess preferences of two children,
      with severe and profound intellectual disabilities. Both children had physical
      challenges and exhibited minimal physical movement. We also compared the relative
      reinforcing effects of the identified high and low preference stimuli for a
      switch pressing response, and for a more passive looking response. High and low
      preference stimuli were identified for both children. Moreover, the high
      preference stimulus maintained higher rates of responding than the low preference
      stimulus for both children for the passive looking response, but not for switch
      pressing. The study extended the use of passive approach to assess preferences
      and identified the choice of target response as a potential limiting factor
      during reinforcer tests for these children.

PMID- 23539236
TI  - Dexamethasone, light anaesthesia, and tight glucose control (DeLiT) randomized
      controlled trial.
AB  - BACKGROUND: The inflammatory response to surgical tissue injury is associated
      with perioperative morbidity and mortality. We tested the primary hypotheses that
      major perioperative morbidity is reduced by three potential anti-inflammatory
      interventions: (i) low-dose dexamethasone, (ii) intensive intraoperative glucose
      control, and (iii) lighter anaesthesia. METHODS: We enrolled patients having
      major non-cardiac surgery who were >=40 yr old and had an ASA physical status
      <=IV. In a three-way factorial design, patients were randomized to perioperative
      i.v. dexamethasone (a total of 14 mg tapered over 3 days) vs placebo, intensive
      vs conventional glucose control 80-110 vs 180-200 mg dl(-1), and lighter vs
      deeper anaesthesia (bispectral index target of 55 vs 35). The primary outcome was
      a collapsed composite of 15 major complications and 30 day mortality. Plasma high
      sensitivity (hs) C-reactive protein (CRP) concentration was measured before
      operation and on the first and second postoperative days. RESULTS: The overall
      incidence of the primary outcome was about 20%. The trial was stopped after the
      second interim analysis with 381 patients, at which all three interventions
      crossed the futility boundary for the primary outcome. No three-way (P=0.70) or
      two-way (all P>0.52) interactions among the interventions were found. There was a
      significantly smaller increase in hsCRP in patients given dexamethasone than
      placebo [maximum 108 (64) vs 155 (69) mg litre(-1), P<0.001], but none of the
      other two interventions differentially influenced the hsCRP response to surgery.
      CONCLUSIONS: Among our three interventions, dexamethasone alone reduced
      inflammation. However, no intervention reduced the risk of major morbidity or 1
      yr mortality. TRIAL REGISTRATION IDENTIFIER: NCT00433251 at
      www.clinicaltrials.gov.

PMID- 23539238
TI  - Bidirectional influences between dimensions of coparenting and adolescent
      adjustment.
AB  - Research on coparenting documents that mothers' and fathers' coordination and
      mutual support in their parenting roles is linked to their offspring's adjustment
      in childhood, but we know much less about the coparenting of adolescents. Taking
      a family systems perspective, this study assessed two dimensions of coparenting,
      parents' shared decision-making and joint involvement in activities with their
      adolescents, and examined bidirectional associations between these coparenting
      dimensions and boys' and girls' risky behaviors and depressive symptoms across
      four time points (6 years) in adolescence. Participants were 201 mothers,
      fathers, and adolescents (M = 11.83, SD = .55 years of age at Time 1; 51%
      female). Parents of sons shared more decisions, on average, than parents of
      daughters. On average, shared decision-making followed an inverted U shaped
      pattern of change, and parents' joint involvement in their adolescents'
      activities declined. Cross-lagged findings revealed that risky behavior predicted
      less shared decision-making, and shared decision-making protected against
      increased risky behavior for boys. For girls and boys, parents' joint involvement
      predicted fewer risky behaviors, and lower levels of risky behavior predicted
      higher levels of joint involvement. In contrast, boys' and girls' depressive
      symptoms predicted less joint involvement. The discussion centers on the nature
      and correlates of coparenting during adolescence, including the role of child
      effects, and directions for future research on coparenting during this
      developmental period.

PMID- 23539240
TI  - Intraocular penetration of penciclovir after oral administration of famciclovir:
      a population pharmacokinetic model.
AB  - OBJECTIVES: We developed a population model that describes the ocular penetration
      and pharmacokinetics of penciclovir in human aqueous humour and plasma after oral
      administration of famciclovir. METHODS: Fifty-three patients undergoing cataract
      surgery received a single oral dose of 500 mg of famciclovir prior to surgery.
      Concentrations of penciclovir in both plasma and aqueous humour were measured by
      HPLC with fluorescence detection. Concentrations in plasma and aqueous humour
      were fitted using a two-compartment model (NONMEM software). Inter-individual and
      intra-individual variabilities were quantified and the influence of demographics
      and physiopathological and environmental variables on penciclovir
      pharmacokinetics was explored. RESULTS: Drug concentrations were fitted using a
      two-compartment, open model with first-order transfer rates between plasma and
      aqueous humour compartments. Among tested covariates, creatinine clearance, co
      intake of angiotensin-converting enzyme inhibitors and body weight significantly
      influenced penciclovir pharmacokinetics. Plasma clearance was 22.8+/-9.1 L/h and
      clearance from the aqueous humour was 8.2*10(-5) L/h. AUCs were 25.4+/-10.2 and
      6.6+/-1.8 MUg.h/mL in plasma and aqueous humour, respectively, yielding a
      penetration ratio of 0.28+/-0.06. Simulated concentrations in the aqueous humour
      after administration of 500 mg of famciclovir three times daily were in the range
      of values required for 50% growth inhibition of non-resistant strains of the
      herpes zoster virus family. CONCLUSIONS: Plasma and aqueous penciclovir
      concentrations showed significant variability that could only be partially
      explained by renal function, body weight and comedication. Concentrations in the
      aqueous humour were much lower than in plasma, suggesting that factors in the
      blood-aqueous humour barrier might prevent its ocular penetration or that
      redistribution occurs in other ocular compartments.

PMID- 23539239
TI  - Co-occurrence of amikacin-resistant and -susceptible Mycobacterium tuberculosis
      isolates in clinical samples from Beijing, China.
AB  - OBJECTIVES: This study examined the phenomenon of heteroresistance in
      Mycobacterium tuberculosis clinical isolates obtained from retreated patients in
      Beijing, China between 2006 and 2011. METHODS: The iPLEX Gold assay platform was
      used to determine the prevalence of heteroresistance to injectable second-line
      drugs (amikacin, kanamycin and capreomycin) in resistant isolates. RESULTS:
      Heteroresistance was identified in 10.9% of 220 phenotypic amikacin-resistant
      isolates. CONCLUSIONS: Heteroresistance was related mainly to the short duration
      and repeated use of amikacin and capreomycin during retreatment. These findings
      further our understanding of the evolution of resistance to injectable drugs used
      for tuberculosis treatment and help guide the rational use of injectable drugs
      during therapy.

PMID- 23539241
TI  - High-level resistance to isoniazid and ethionamide in multidrug-resistant
      Mycobacterium tuberculosis of the Lisboa family is associated with inhA double
      mutations.
AB  - OBJECTIVES: The purpose of this study was to determine the levels of isoniazid
      and ethionamide resistance and to identify associated mutations in endemic
      multidrug-resistant (MDR) strains of Mycobacterium tuberculosis from the Lisbon
      metropolitan area, Portugal. METHODS: Seventeen clinical MDR tuberculosis (TB)
      strains were characterized by standard and semi-quantitative drug susceptibility
      testing to assess the level of isoniazid and ethionamide resistance. The genes
      katG, inhA, ethA and ndh were screened for mutations. All strains were genotyped
      by 24 loci mycobacterial interspersed repetitive unit-variable number of tandem
      repeats (MIRU-VNTR) analysis. RESULTS: All strains showed high-level resistance
      to both isoniazid (>1 mg/L) and ethionamide (>25 mg/L). MIRU-VNTR typing revealed
      the presence of two main clusters, Lisboa3 and Q1, in 16/17 strains, all of which
      showed the C-15T mutation in the promoter region of the inhA gene. The 16 strains
      belong to the Latino-American-Mediterranean (LAM) genotype and the other strain
      belongs to the Beijing genotype. Sequencing of the inhA open reading frame
      revealed that the 16 strains also had mutations in the structural region of the
      gene, leading to the S94A substitution in 9 strains and the I194T substitution in
      7 strains. CONCLUSIONS: The results reveal that the presence of a mutation in the
      inhA regulatory region together with a mutation in the inhA coding region can
      lead to the development of high-level isoniazid resistance and cross-resistance
      to ethionamide among the MDR-TB strains circulating in Lisbon. This mutational
      pattern also hints to a possible involvement of strain-specific factors that
      could be a feature of the Portuguese MDR-TB strains where the LAM family is the
      major circulating genotype.

PMID- 23539242
TI  - Tangibles, Pictures, and Verbal Descriptions: Which Should Be Used in Choice
      Presentations?
AB  - Little research has examined how stimulus modalities influence choice responding.
      Should choice alternatives be presented using tangibles, pictures, or verbal
      descriptions? How should caregivers decide which modality to use? We have
      completed several studies to examine how discrimination skills, as measured by
      the Assessment of Basic Learning Abilities test, interact with choice stimulus
      modalities to influence responding. Our results suggest that for persons with
      developmental disabilities with limited or no communication skills, the ability
      to make simple visual, visual matching to sample, and auditory-visual
      discriminations should be the prime determinant of stimulus modalities in choice
      presentation and preference assessment.

PMID- 23539243
TI  - betaIII-Gal is involved in galactan reduction during phloem element
      differentiation in chickpea stems.
AB  - betaIII-Gal, a member of the chickpea beta-galactosidase family, is the enzyme
      responsible for the cell wall autolytic process. This enzyme, whose activity
      increases during epicotyl growth, displays significant hydrolytic activity
      against cell wall pectins, and its natural substrate has been determined as an
      arabinogalactan from the pectic fraction of the cell wall. In the present work,
      the localization of betaIII-Gal in different seedling and plant organs was
      analyzed by using specific anti-betaIII-Gal antibodies. Our results revealed that
      besides its possible role in cell wall loosening and in early events during
      primary xylem and phloem fiber differentiation betaIII-Gal acts on the
      development of sieve elements. Localization of the enzyme in this tissue, both in
      epicotyls and radicles from seedlings and in the different stem internodes, is
      consistent with the reduction in galactan during the maturation of phloem
      elements, as can be observed with LM5 antibodies. Thus, betaIII-Gal could act on
      its natural substrate, the neutral side chains of rhamnogalacturonan I,
      contributing to cell wall reinforcement allowing phloem elements to
      differentiate, and conferring the necessary strengthening of the cell wall to
      fulfill its function. This work completes the immunolocation studies of all known
      chickpea beta-galactosidases. Taken together, our results reflect the broad range
      of developmental processes covered by different members of this protein family,
      and confirm their crucial role in cell wall remodeling during tissue
      differentiation.

PMID- 23539244
TI  - Cytokinin response factor 6 negatively regulates leaf senescence and is induced
      in response to cytokinin and numerous abiotic stresses.
AB  - Cytokinin response factor 6 (CRF6) is an Arabidopsis AP2/ERF transcription factor
      which is transcriptionally induced by cytokinin. Cytokinin is known to delay leaf
      senescence in wild-type (WT) plants, for example in dark-incubated detached
      leaves. This response is mediated by the cytokinin receptor Arabidopsis histidine
      kinase receptor 3 (AHK3). Similar to ahk3 mutants, crf6 leaves show decreased
      sensitivity to this cytokinin effect. Leaves overexpressing CRF6 retain more Chl
      than those of the WT under these conditions without exogenous cytokinin. It
      therefore appears that an increase in expression of CRF6 downstream of the
      perception of cytokinin by AHK3 is involved in the delay of leaf senescence.
      Intact crf6 plants also begin to undergo monocarpic senescence sooner than WT
      plants. Interestingly, plants overexpressing CRF6 display a more extreme
      acceleration of development than crf6 mutants, suggesting that a specific
      expression level or localization of CRF6 is necessary to prevent premature
      senescence. Expression analyses indicate that CRF6 is highly expressed in the
      veins of mature leaves and that this expression decreases with age. CRF6
      expression is shown to be induced by abiotic stress, in addition to increased
      cytokinin. Together, these findings suggest that CRF6 functions to regulate
      developmental senescence negatively and may have a similar role in response to
      stress. CRF6 may therefore be involved in fine-tuning the timing of developmental
      and stress-induced senescence. CRF6 functioning in negative regulation of
      senescence is significant in that it is the first process known to be regulated
      by cytokinin, in which a CRF can be placed specifically downstream of the
      cytokinin signaling pathway.

PMID- 23539245
TI  - Transgenic rice seeds accumulating recombinant hypoallergenic birch pollen
      allergen Bet v 1 generate giant protein bodies.
AB  - A versatile hypoallergenic allergen derivative against multiple allergens is an
      ideal tolerogen for allergen-specific immunotherapy. Such a tolerogen should
      exhibit high efficacy, without side effects, when administered at high doses and
      should be applicable to several allergens. Tree pollen chimera 7 (TPC7), a
      hypoallergenic Bet v 1 tolerogen against birch pollen allergy, was previously
      selected by DNA shuffling of 14 types of Fagales tree pollen allergens. In this
      study, transgenic rice seed accumulating TPC7 was generated as an oral vaccine
      against birch pollen allergy by expressing this protein as a secretory protein
      using the N-terminal signal peptide and the C-terminal KDEL tag under the control
      of an endosperm-specific glutelin promoter. The highest level of TPC7
      accumulation was approximately 207 ug grain(-1). Recombinant TPC7 is a
      glycoprotein with high mannose-type N-glycan, but without beta1,2-xylose or
      alpha1,3-fucose, suggesting that TPC7 is retained in the endoplasmic reticulum
      (ER). TPC7 is deposited as a novel, giant spherical ER-derived protein body, >20
      um in diameter, which is referred to as the TPC7 body. Removal of the KDEL
      retention signal or mutation of a cysteine residue resulted in an alteration of
      TPC7 body morphology, and deletion of the signal peptide prevented the
      accumulation of TPC7 in rice seeds. Therefore, the novel TPC7 bodies may have
      formed aggregates within the ER lumen, primarily due to the intrinsic
      physicochemical properties of the protein.

PMID- 23539246
TI  - Complications associated with injectable soft-tissue fillers: a 5-year
      retrospective review.
AB  - IMPORTANCE: Even when administered by experienced hands, injectable soft-tissue
      fillers can cause various unintended reactions, ranging from minor and self
      limited responses to severe complications requiring prompt treatment and close
      follow-up. OBJECTIVES: To review the complications associated with injectable
      soft-tissue filler treatments administered in the Williams Rejuva Center during a
      5-year period and to discuss their management. DESIGN AND SETTING: Retrospective
      medical record review in a private practice setting. PARTICIPANTS: Patients
      receiving injectable soft-tissue fillers and having a treatment-related
      complication. INTERVENTIONS: Injectable soft-tissue filler treatments. MAIN
      OUTCOME MEASURES: A retrospective medical record review was conducted of patients
      undergoing treatment with injectable soft-tissue fillers between January 1, 2007,
      and December 31, 2011, and identified as having a treatment-related complication.
      RESULTS: A total of 2089 injectable soft-tissue filler treatments were performed
      during the study period, including 1047 with hyaluronic acid, 811 with poly-L
      lactic acid, and 231 with calcium hydroxylapatite. Fourteen complications were
      identified. The most common complication was nodule or granuloma formation.
      Treatment with calcium hydroxylapatite had the highest complication rate.
      CONCLUSIONS AND RELEVANCE: Complications are rare following treatment with
      injectable soft-tissue fillers. Nevertheless, it is important to be aware of the
      spectrum of potential adverse sequelae and to be comfortable with their proper
      management. LEVEL OF EVIDENCE: 4.

PMID- 23539248
TI  - Use of continuous hemodiafiltration for the treatment of a neonate with
      hyperammonemia secondary to argininosuccinate lyase (ASAL) deficiency.

PMID- 23539249
TI  - The association between vitamin D status and recurrent wheezing.
AB  - OBJECTIVE: To investigate association between vitamin D status and recurrent
      wheezing in infants. METHODS: Thirty infants with recurrent wheezing and 45
      healthy, similar aged infants without any history of acute or chronic illness
      were included in the study. The clinical features of infants were recorded and
      serum 25-hydroxyvitamin D [25(OH)D] levels were measured. Data analysis was
      performed using SPSS 13 package program. RESULTS: The mean value of 25 (OH) D
      vitamin levels were 22.1 +/- 8.9 IU/L and 18.8 +/- 11 IU/L for the control and
      recurrent attack group respectively. Seventy-three percent of subjects with
      recurrent wheezing had vitamin D levels in the deficient range (<20 ng/ml) and
      48.9 % had vitamin D levels under < 20 ng/ml in the control group. The percentage
      of insufficient vitamin D levels (<30 ng/ml) were 90 and 77.8 for the patient and
      control group respectively. Eight patients had extremely deficient vitamin D (<10
      ng/ml) levels. There was no statistical significance between the groups in terms
      of the distribution of 25 (OH)D level. CONCLUSIONS: The present study did not
      demonstrate significant association between vitamin D status and recurrent
      wheezing in the infants.

PMID- 23539250
TI  - Acute renal failure in tetanus.

PMID- 23539251
TI  - Bacteremia caused by Rhizobium radiobacter in a preterm neonate.
AB  - The authors report a case of bacteremia due to Rhizobium radiobacter in a preterm
      neonate. Although the baby recovered from the septic episode following therapy
      with appropriate antibiotics he succumbed to complications, mainly associated
      with prematurity. This case highlights a rare manifestation of R.radiobacter
      infection in a neonate in whom the source of the organism remained undiscovered. 

PMID- 23539252
TI  - Adolescent sleep problems and behavior: a school survey.

PMID- 23539253
TI  - Blood lead levels among school children after phasing-out of leaded petrol in
      Delhi, India.
AB  - OBJECTIVES: The use of leaded petrol was prohibited in the Delhi city by the end
      of 1998. To determine the impact of use of unleaded petrol, this cross-sectional
      study was conducted to determine blood lead levels in primary school children.
      METHODS: Blood lead levels were estimated in 300 school children aged 6 to 10 y.
      The data regarding clinical features and putative risk factors for high blood
      lead levels was also collected. RESULTS: Of the 300 children, 36 (12 %) had high
      blood lead levels. Of the 36 children, 32 had blood lead levels between 10 and 19
      MUg/dl, 4 had 20-44 MUg/dl and none had levels >45 MUg/dl. Factors such as
      exposure to peeling paint, recent renovation of housing and near-distance of
      house to main road were significantly associated with high blood lead levels.
      CONCLUSIONS: There is significant prevalence of high blood lead levels in school
      children in Delhi, even after with prohibition of use of leaded petrol.

PMID- 23539254
TI  - Isolated fat-containing pancreatic metastasis from hepatocellular carcinoma.
AB  - We report a case of a 50-year-old male with isolated pancreatic metastasis from
      hepatocellular carcinoma (HCC), in which chemical shift magnetic resonance
      imaging detected the presence of fat, and which mimicked fatty replacement. A
      solitary metastatic pancreatic tumor originating from HCC is very rare.
      Furthermore, we believe that this is the first report of fat-containing
      pancreatic metastasis from HCC.

PMID- 23539255
TI  - Comparison of short- and long-term outcomes of laparoscopic-assisted total
      gastrectomy and open total gastrectomy in gastric cancer patients.
AB  - BACKGROUND: Laparoscopy-assisted total gastrectomy (LATG) has been used more
      frequently despite the associated technical difficulty and concerns over
      oncological safety. This study was undertaken to compare the short- and long-term
      surgical outcomes following either LATG or open total gastrectomy (OTG) for
      gastric cancer. METHODS: A total of 120 LATG and 228 OTG were retrospectively
      matched with respect to sex, age (+/-5 years), and pathological tumor-node
      metastasis stage for comparison of the clinical outcomes. RESULTS: The total
      complication rate among 120 LATG and 228 OTG was 18.3 % (22/120) and 16.2 %
      (37/228), respectively. The most common complication after LATG was anastomotic
      related complication (6.7 %); five anastomotic leakages (4.2 %) and three
      anastomotic strictures were reported (2.5 %). That after OTG was wound
      complication (3.5 %), including seroma or infection. Matched patients analysis:
      Time to first gas passing and time to the resumption of a soft diet were
      significantly shorter in the LATG group than in the OTG group. The postoperative
      hospital stay of LATG was shorter in the LATG group (9.3 +/- 4.2 days) than in
      the OTG group (11.7 +/- 7.3 days; p = 0.057). Among matched patients, there was
      no significant difference between complication rate (24 vs. 32 %; p = 0.504) or
      leakage rate (6 vs. 4 %). During median follow-up of 50 (range, 10-92) months,
      there was no significant difference in the disease-free survival rate between the
      matched groups, respectively (94.5 vs. 87.1 %: p = 0.148). As for patients with
      TNM stage I gastric cancer, the disease-free survival rate (100 vs. 90.9 %; p =
      0.5) and the cumulative survival rate (91.5 vs. 95.2 %; p = 0.618) did not differ
      significantly between the LATG and OTG groups. CONCLUSIONS: LATG for gastric
      cancer has the advantage over an OTG in terms of better short-term outcomes and
      similar long-term outcome. LATG is an acceptable alternative to OTG for the
      treatment of gastric cancer.

PMID- 23539256
TI  - Carbon dioxide gas pneumoperitoneum induces minimal microcirculatory changes in
      neonates during laparoscopic pyloromyotomy.
AB  - BACKGROUND: Little is known about the direct effect of pneumoperitoneum (PP) on
      microcirculation and its influence on the quality of tissue perfusion. This study
      aimed to investigate the intraoperative effects of carbon dioxide (CO2) gas PP on
      microcirculation density and perfusion in neonates receiving laparoscopic surgery
      for hypertrophic pyloric stenosis. METHODS: In a single-center observational
      study, the oral microcirculation in 12 neonates receiving laparoscopic
      pyloromyotomy was investigated. Intraoperative hemodynamic parameters,
      intermittent buccal mucosa capillary density measurements (pre- and
      postoperative), and continuous intraoperative sublingual microcirculation
      measurements (i.e., vessels with a diameter <25 MUm) of total vessel density,
      perfused vessel density, proportion of perfused blood vessels, blood vessel
      diameters (BVd), and microvascular flow index were obtained before (at baseline),
      during, and after PP insufflation for all patients using sidestream dark-field
      imaging for the duration of the complete surgical procedure. RESULTS: With the
      exception of a significantly elevated end-tidal CO2 (34 +/- 4-40 +/- 8 mmHg; p <
      0.05 vs before [baseline], one-way analysis of variance [ANOVA]) during
      intraoperative insufflation, no significant differences were found between time
      points for the intraoperative hemodynamic parameters. Pre- and postoperative
      buccal capillary density showed no significant changes in mucosal perfusion.
      Analysis of continuous intraoperative sublingual microcirculation parameters
      exhibited a statistically significant increase in BVd during insufflation (8.8 +/
      2.4-9.3 +/- 2.5 MUm; p < 0.05, one-way ANOVA) and a significant decrease after
      exsufflation (8.2 +/- 2.3 MUm; p < 0.01 vs during insufflation and p < 0.05 vs
      baseline, one-way ANOVA, respectively). No other significant differences were
      found between time points for the remaining microcirculatory parameters.
      CONCLUSION: The installation of CO2 gas PP during laparoscopic pyloromyotomy
      procedures regulates microcirculatory perfusion by inducing changes in
      microvascular diameters but does not alter microcirculation density in neonates.

PMID- 23539257
TI  - Effect of prucalopride on the pharmacokinetics of oral contraceptives in healthy
      women.
AB  - BACKGROUND: Prucalopride is a selective, high-affinity, 5-hydroxytryptamine 4 (5
      HT4) receptor agonist, which is approved for the symptomatic treatment of chronic
      constipation in women in whom laxatives fail to provide adequate relief. Women of
      childbearing potential, many of whom will be using oral contraceptives, comprise
      a large proportion of patients seeking medical therapy for constipation.
      OBJECTIVE: The aim of this study was to evaluate the effect of prucalopride on
      the absorption and steady-state pharmacokinetics of oral contraceptives in
      healthy women. METHODS: Sixteen women (aged 18-45 years) were enrolled in this
      open-label, two-way crossover trial (ClinicalTrials.gov identifier: NCT01036893)
      and given two 5-day treatments with a once-daily oral contraceptive
      (ethinylestradiol 0.035 mg + norethisterone 1 mg), alone and in combination with
      prucalopride 2 mg once daily. Treatments were separated by a 7 +/- 2-day washout
      period. On days 1 and 5, blood samples were obtained pre-dose and at regular
      intervals post-dose up to 24 and 48 hours, respectively, to determine
      ethinylestradiol and norethisterone plasma concentrations. Prucalopride plasma
      concentrations were determined pre-dose and 3 hours post-dose on days 1 and 5,
      and 24 hours post-dose on day 6. Safety was assessed. RESULTS: Thirteen
      participants completed the study. One participant was thought to be non-compliant
      on days 3 and/or 4, and was excluded from the day 5 analysis. On days 1 and 5,
      maximum plasma concentrations of both oral contraceptive constituents were
      attained in ~1 hour and were unaffected by prucalopride administration. On day 5,
      steady-state prucalopride and oral contraceptive concentrations had been
      achieved. Prucalopride did not affect the pharmacokinetics of the oral
      contraceptives: point estimates for the maximum plasma concentration and area
      under the plasma concentration-time curve values and their associated 90 %
      confidence intervals were contained within predefined equivalence limits (80-125
      %). Prucalopride was well tolerated, with a safety profile consistent with those
      observed in previous studies. CONCLUSION: Co-administration of prucalopride with
      an oral contraceptive did not result in any clinically meaningful pharmacokinetic
      interactions and was well tolerated.

PMID- 23539258
TI  - Effects of Choice of Work Tasks on On-Task, Aberrant, Happiness and Unhappiness
      Behaviours of Persons with Developmental Disabilities.
AB  - Effects of choice versus no choice of work tasks on work performance,
      inappropriate behaviours, happiness and unhappiness indices were examined in
      three studies. Study 1 examined the effects of a choice between a high and a low
      preference task, versus the assignment of the high preference task. Study 2 was
      similar to Study 1 except that the tasks in the choice condition were equally and
      moderately preferred. Study 3 was conducted by the participants' instructors in
      their natural work settings. A total of five participants were involved across
      the three studies. Very few differences were found under the choice and no-choice
      conditions. More research is needed to examine the role of reinforcement history
      in establishing stimulus control effects of choice.

PMID- 23539259
TI  - A systematic review of electric-acoustic stimulation: device fitting ranges,
      outcomes, and clinical fitting practices.
AB  - Cochlear implant systems that combine electric and acoustic stimulation in the
      same ear are now commercially available and the number of patients using these
      devices is steadily increasing. In particular, electric-acoustic stimulation is
      an option for patients with severe, high frequency sensorineural hearing
      impairment. There have been a range of approaches to combining electric
      stimulation and acoustic hearing in the same ear. To develop a better
      understanding of fitting practices for devices that combine electric and acoustic
      stimulation, we conducted a systematic review addressing three clinical
      questions: what is the range of acoustic hearing in the implanted ear that can be
      effectively preserved for an electric-acoustic fitting?; what benefits are
      provided by combining acoustic stimulation with electric stimulation?; and what
      clinical fitting practices have been developed for devices that combine electric
      and acoustic stimulation? A search of the literature was conducted and 27
      articles that met the strict evaluation criteria adopted for the review were
      identified for detailed analysis. The range of auditory thresholds in the
      implanted ear that can be successfully used for an electric-acoustic application
      is quite broad. The effectiveness of combined electric and acoustic stimulation
      as compared with electric stimulation alone was consistently demonstrated,
      highlighting the potential value of preservation and utilization of low frequency
      hearing in the implanted ear. However, clinical procedures for best fitting of
      electric-acoustic devices were varied. This clearly identified a need for further
      investigation of fitting procedures aimed at maximizing outcomes for recipients
      of electric-acoustic devices.

PMID- 23539260
TI  - Perception of pure tones and iterated rippled noise for normal hearing and
      cochlear implant users.
AB  - Cochlear Implant (CI) users typically perform poorly on musical tasks, especially
      those based on pitch ranking and melody recognition. It was hypothesized that CI
      users would demonstrate deterioration in performance for a pitch ranking and a
      melody recognition task presented with iterated rippled noise (IRN) in comparison
      to pure tones (PT). In Addition, it was hypothesized that normal hearing (NH)
      listeners would show fewer differences in performance between IRN and PT for
      these two tasks. In this study, the ability of CI users and NH subjects to rank
      pitches and to identify melodies created with IRN and PT was assessed in free
      field in a sound-isolated room. CI subjects scored significantly above chance
      level with PT stimuli in both tasks. With IRN stimuli their performance was
      around chance level. NH subjects scored significantly above chance level in both
      tasks and with all stimuli. NH subjects performed significantly better than CI
      subjects in both tasks. These results illustrate the difficulties of CI subjects
      to rank pitches and to identify melodies.

PMID- 23539262
TI  - Unstable microhabitats (merocenoses) as specific habitats of Uropodina mites
      (Acari: Mesostigmata).
AB  - Unstable microhabitats (merocenoses)--such as decayed wood, ant hills, bird and
      mammal nests--constitute an important component of forest (and non-forest)
      environments. These microhabitats are often inhabited by specific communities of
      invertebrates and their presence increases the total biodiversity. The primary
      objective of the present study was to compare communities of Uropodina (Acari:
      Mesostigmata) inhabiting soil and unstable microhabitats in order to explore the
      specificity of these communities and their importance in such ecosystems.
      Uropodine communities inhabiting merocenoses are often predominated by one or two
      species, which constitute more than 50 % of the entire community. Many species
      occur commonly in particular merocenoses, but are absent or rare in soil and
      litter, for example, Allodinychus flagelliger, Metagynella carpatica, Oplitis
      alophora, and Phaulodiaspis borealis. The biology of Uropodina inhabiting
      unstable microhabitats is modified by the adaptations required for living in such
      habitats. Mites associated with merocenoses developed special dispersal
      mechanisms, such as phoresy, which enable them to migrate from disappearing
      environments. Communities of Uropodina in soil and litter predominately consisted
      of species which reproduce parthenogenetically (thelytoky), whereas in
      merocenoses bisexual species prevail.

PMID- 23539261
TI  - Nonlinear frequency compression: effects on sound quality ratings of speech and
      music.
AB  - Frequency lowering technologies offer an alternative amplification solution for
      severe to profound high frequency hearing losses. While frequency lowering
      technologies may improve audibility of high frequency sounds, the very nature of
      this processing can affect the perceived sound quality. This article reports the
      results from two studies that investigated the impact of a nonlinear frequency
      compression (NFC) algorithm on perceived sound quality. In the first study, the
      cutoff frequency and compression ratio parameters of the NFC algorithm were
      varied, and their effect on the speech quality was measured subjectively with 12
      normal hearing adults, 12 normal hearing children, 13 hearing impaired adults,
      and 9 hearing impaired children. In the second study, 12 normal hearing and 8
      hearing impaired adult listeners rated the quality of speech in quiet, speech in
      noise, and music after processing with a different set of NFC parameters. Results
      showed that the cutoff frequency parameter had more impact on sound quality
      ratings than the compression ratio, and that the hearing impaired adults were
      more tolerant to increased frequency compression than normal hearing adults. No
      statistically significant differences were found in the sound quality ratings of
      speech-in-noise and music stimuli processed through various NFC settings by
      hearing impaired listeners. These findings suggest that there may be an
      acceptable range of NFC settings for hearing impaired individuals where sound
      quality is not adversely affected. These results may assist an Audiologist in
      clinical NFC hearing aid fittings for achieving a balance between high frequency
      audibility and sound quality.

PMID- 23539263
TI  - Career development through local chapter involvement: perspectives from chapter
      members.
AB  - The importance of career development in professional organizations has been noted
      in the literature. Personal and professional benefits of membership regardless of
      discipline can be found across the career spectrum from student to executive. The
      benefits of professional membership with respect to career development in local
      chapter organizations have seldom been studied. Local chapter participation may
      offer significant career development opportunities for the practitioner, faculty
      member, and student. The purpose of this study was to explore the importance of
      local chapter involvement to the career development of health education
      practitioners. An 18-item questionnaire was disseminated to the membership of
      three local SOPHE (Society for Public Health Education) chapters that explored
      the level of local chapter involvement and the impact of how specific
      professional development activities impacted career development. The results of
      the survey highlighted the importance of continuing education programs,
      networking, and leadership experience in developing one's career that are offered
      by local SOPHE chapter involvement. Making a positive impact in the community and
      earning the respect of one's peers were most often reported as indicators of
      career success. These factors can directly impact local chapter participation.
      Career development can certainly be enhanced by active participation in the local
      chapter of a professional association.

PMID- 23539265
TI  - Comparing the utility of the theory of planned behavior between boys and girls
      for predicting snack food consumption: implications for practice.
AB  - The purpose of this study was to use the theory of planned behavior to explain
      two types of snack food consumption among boys and girls (girls n = 98; boys n =
      69), which may have implications for future theory-based health promotion
      interventions. Between genders, there was a significant difference for calorie
      dense/nutrient-poor snacks (p = .002), but no difference for fruit and vegetable
      snacks. Using stepwise multiple regression, attitudes, perceived behavioral
      control, and subjective norms accounted for a large amount of the variance of
      intentions (girls = 43.3%; boys = 55.9%); however, for girls, subjective norms
      accounted for the most variance, whereas for boys, attitudes accounted for the
      most variance. Calories from calorie-dense/nutrient-poor snacks and fruit and
      vegetable snacks were also predicted by intentions. For boys, intentions
      predicted 6.4% of the variance for fruit and vegetable snacks (p = .03) but was
      not significant for calorie-dense/nutrient-poor snacks, whereas for girls,
      intentions predicted 6.0% of the variance for fruit and vegetable snacks (p =
      .007), and 7.2% of the variance for calorie-dense/nutrient-poor snacks (p =
      .004). Results suggest that the theory of planned behavior is a useful framework
      for predicting snack foods among children; however, there are important
      differences between genders that should be considered in future health promotion
      interventions. 

PMID- 23539264
TI  - Translating an evidence-based lifestyle intervention program into primary care:
      lessons learned.
AB  - The E-LITE (Evaluation of Lifestyle Interventions to Treat Elevated
      Cardiometabolic Risk in Primary Care) trial evaluated the feasibility and
      potential effectiveness of translating an evidence-based lifestyle intervention
      for the management of obesity and related risk factors in a primary care setting.
      Delivered by allied health care providers, the intervention promoted at least 7%
      weight loss and at least 150 minutes per week of moderate-intensity physical
      activity through gradual, sustainable lifestyle changes. Activities included
      interactive group lessons, food tasting, guided physical activity, and technology
      mediated self-monitoring and behavioral counseling. This article discusses
      insights and potential areas for improvement to strengthen program implementation
      for dissemination of the E-LITE program to other primary care settings. We focus
      on (a) the role of allied health professionals in program delivery, (b)
      strengthening program integration within a primary care clinic, and (c) the use
      of information technology to extend the reach and impact of the program. Our
      experience shows the feasibility of implementing an evidence-based lifestyle
      intervention program combining group-delivered nutrition and behavioral
      counseling, physical activity training, and technology-mediated follow-up in a
      primary care setting. Challenges remain, and we offer possible solutions to
      overcome them.

PMID- 23539266
TI  - Using the give-get grid to understand potential expectations of engagement in a
      community-academic partnership.
AB  - Research suggests that stakeholder investment is maximized when partnerships
      understand the assumptions held by partners of the benefits to be derived and
      contributions to be made to the partnership. In 2011, representatives from seven
      rural county high schools and five university departments participated in a
      planning workshop designed to identify elements of an effective community
      academic partnership to address adolescent obesity disparity in Southern
      Appalachia. The purpose of this investigation was to examine key elements of
      partnership building by way of the Give-Get Grid partnership tool. Content
      analysis was conducted to identify emerging themes. University representatives
      consistently identified more proposed program contributions as well as benefits
      than their high school partners. University personnel responses generally
      pertained to their level of participation and investment in the partnership,
      whereas high school personnel tended to identify contributions fundamental to
      both partnership and program success. Additionally, content analysis uncovered
      programmatic facilitators and potential barriers that can be instrumental in
      program planning and forming program messages. Findings suggest that although
      partners often share common goals, perceptions of the value of investment and
      benefits may vary. The Give-Get Grid can be used during the program-planning
      phase to help identify these differences. Implications for practice are
      discussed. 

PMID- 23539267
TI  - Sources of Cognitive Inflexibility in Set-Shifting Tasks: Insights Into
      Developmental Theories From Adult Data.
AB  - Two experiments examined processes underlying cognitive inflexibility in set
      shifting tasks typically used to assess the development of executive function in
      children. Adult participants performed a Flexible Item Selection Task (FIST) that
      requires shifting from categorizing by one dimension (e.g., color) to
      categorizing by a second orthogonal dimension (e.g., shape). The experiments
      showed performance of the FIST involves suppression of the representation of the
      ignored dimension; response times for selecting a target object in an immediately
      following oddity task were slower when the oddity target was the previously
      ignored stimulus of the FIST. However, proactive interference from the previously
      relevant stimulus dimension also impaired responding. The results are discussed
      with respect to two prominent theories of the source of difficulty for children
      and adults on dimensional shifting tasks: attentional inertia and negative
      priming. In contrast to prior work emphasizing one over the other process, the
      findings indicate that difficulty in the FIST, and by extension other set
      shifting tasks, can be attributed to both the need to shift away from the
      previously attended representation (attentional inertia), and the need to shift
      to the previously ignored representation (negative priming). Results are
      discussed in relation to theoretical explanations for cognitive inflexibility in
      adults and children.

PMID- 23539268
TI  - Exogenous bone morphogenetic protein-7 reduces hepatic fibrosis in Schistosoma
      japonicum-infected mice via transforming growth factor-beta/Smad signaling.
AB  - AIM: To investigate the antifibrotic effects of bone morphogenetic protein-7 (BMP
      7) on Schistosoma japonicum (S. japonicum)-induced hepatic fibrosis in BALB/C
      mice. METHODS: Sixty BALB/C mice were randomly divided into three groups,
      including a control group (group A, n = 20), model group (group B, n = 20) and
      BMP-7 treated group (group C, n = 20). The mice in group B and group C were
      abdominally infected with S. japonicum cercariae to induce a schistosomal hepatic
      fibrosis model. The mice in group C were administered human recombinant BMP-7.
      Liver samples were extracted from mice sacrificed at 9 and 15 wk after modeling.
      Hepatic histopathological changes were assessed using Masson's staining.
      Transforming growth factor-beta 1 (TGF-beta1), alpha-smooth muscle actin (alpha
      SMA), phosphorylated Smad2/3 (pSmad2/3) and Smad7 protein levels and localization
      were measured by Western blotting and immunohistochemistry, respectively, and
      their mRNA expressions were detected by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: The schistosomal hepatic fibrosis mouse model was
      successfully established, as the livers of mice in group B and group C showed
      varying degrees of typical schistosomal hepatopathologic changes such as egg
      granuloma and collagen deposition. The degree of collagen deposition in group C
      was higher than that in group A (week 9: 22.95 +/- 6.66 vs 2.02 +/- 0.76; week
      15: 12.84 +/- 4.36 vs 1.74 +/- 0.80; P < 0.05), but significantly lower than that
      in group B (week 9: 22.95 +/- 6.66 vs 34.43 +/- 6.96; week 15: 12.84 +/- 4.36 vs
      18.90 +/- 5.07; P < 0.05) at both time points. According to immunohistochemistry
      data, the expressions of alpha-SMA, TGF-beta1 and pSmad2/3 protein in group C
      were higher than those in group A (alpha-SMA: week 9: 21.24 +/- 5.73 vs 0.33 +/-
      0.20; week 15: 12.42 +/- 4.88 vs 0.34 +/- 0.27; TGF-beta1: week 9: 37.00 +/-
      13.74 vs 3.73 +/- 2.14; week 15: 16.71 +/- 9.80 vs 3.08 +/- 2.35; pSmad2/3: week
      9: 12.92 +/- 4.81 vs 0.83 +/- 0.48; week 15: 7.87 +/- 4.09 vs 0.90 +/- 0.45; P <
      0.05), but significantly lower than those in group B (alpha-SMA: week 9: 21.24 +/
      5.73 vs 34.39 +/- 5.74; week 15: 12.42 +/- 4.88 vs 25.90 +/- 7.01; TGF-beta1:
      week 9: 37.00 +/- 13.74 vs 55.66 +/- 14.88; week 15: 16.71 +/- 9.80 vs 37.10 +/-
      12.51; pSmad2/3: week 9: 12.92 +/- 4.81 vs 19.41 +/- 6.87; week 15: 7.87 +/- 4.09
      vs 13.00 +/- 4.98; P < 0.05) at both time points; the expression of Smad7 protein
      in group B was higher than that in group A and group C at week 9 (8.46 +/- 3.95
      vs 1.00 +/- 0.40 and 8.46 +/- 3.95 vs 0.77 +/- 0.42; P < 0.05), while there were
      no differences in Smad7 expression between the three groups at week 15 (1.09 +/-
      0.38 vs 0.97 +/- 0.42 vs 0.89 +/- 0.39; P > 0.05). Although minor discrepancies
      were observed, the results of RT-PCR and Western blotting were mainly consistent
      with the immunohistochemical results. CONCLUSION: Exogenous BMP-7 significantly
      decreased the degree of hepatic fibrosis in both the acute and chronic stages of
      hepato-schistosomiasis, and the regulatory mechanism may involve the TGF
      beta/Smad signaling pathway.

PMID- 23539269
TI  - Histone H3.3. mutations drive pediatric glioblastoma through upregulation of
      MYCN.
AB  - Children and young adults with glioblastoma (GBM) have a median survival rate of
      only 12 to 15 months, and these GBMs are clinically and biologically distinct
      from histologically similar cancers in older adults. They are defined by highly
      specific mutations in the gene encoding the histone H3.3 variant H3F3A ,
      occurring either at or close to key residues marked by methylation for regulation
      of transcription-K27 and G34. Here, we show that the cerebral hemisphere-specific
      G34 mutation drives a distinct expression signature through differential genomic
      binding of the K36 trimethylation mark (H3K36me3). The transcriptional program
      induced recapitulates that of the developing forebrain, and involves numerous
      markers of stem-cell maintenance, cell-fate decisions, and self
      renewal.Critically, H3F3A G34 mutations cause profound upregulation of MYCN , a
      potent oncogene that is causative of GBMs when expressed in the correct
      developmental context. This driving aberration is selectively targetable in this
      patient population through inhibiting kinases responsible for stabilization of
      the protein. SIGNIFICANCE: We provide the mechanistic explanation for how the fi
      rst histone gene mutation inhuman disease biology acts to deliver MYCN, a potent
      tumorigenic initiator, into a stem-cell compartment of the developing forebrain,
      selectively giving rise to incurable cerebral hemispheric GBM. Using synthetic
      lethal approaches to these mutant tumor cells provides a rational way to develop
      novel and highly selective treatment strategies

PMID- 23539270
TI  - Crystal structure of a type II dehydroquinate dehydratase-like protein from
      Bifidobacterium longum.
AB  - Dehydroquinate dehydratase (DHQD) catalyzes the third step in the biosynthetic
      shikimate pathway. Here we identify a Bifidobacterium longum protein with high
      sequence homology to type II DHQDs but no detectable DHQD activity under standard
      assay conditions. A crystal structure reveals that the B. longum protein adopts a
      DHQD-like tertiary structure but a distinct quaternary state. Apparently forming
      a dimer, the B. longum protein lacks the active site aspartic acid contributed
      from a neighboring protomer in the type II DHQD dodecamer. Relating to the
      absence of protein-protein interactions established in the type II DHQD
      dodecameric assembly, substantial conformational changes distinguish the would-be
      active site of the B. longum protein. As B. longum possess no other genes with
      homology to known DHQDs, these findings imply a unique DHQD activity within B.
      longum.

PMID- 23539271
TI  - Decreased serum level of IL-21 in new-onset systemic lupus erythematosus
      patients.
AB  - This study aims to investigate the serum IL-21 levels in systemic lupus
      erythematosus (SLE) and its relations with clinical and laboratory features.
      Fifty-seven patients with SLE and 30 healthy volunteers were recruited in the
      current study. Serum IL-21 levels were detected by enzyme-linked immunosorbent
      assay. Statistical analyses were performed by SPSS 10.01. Results showed that IL
      21 levels were significantly decreased in the serum of patients with SLE compared
      with controls (P = 0.026). There was no significant difference regarding serum IL
      21 level between SLE patients with nephritis and those without nephritis (P =
      0.066); no significant difference was found between less active SLE and more
      active SLE (P = 0.588). The presence of anemia was associated with low serum IL
      21 levels (P = 0.030) in SLE patients. In summary, decreased serum level of IL-21
      and its association with anemia indicate a possible role of IL-21 in human SLE.
      However, further studies are needed to confirm this preliminary results.

PMID- 23539272
TI  - Core set of recommendations for patients with ankylosing spondylitis concerning
      behaviour and environmental adaptations.
AB  - Advice concerning behaviour and adaptations of living and working environment is
      considered an unmet need by patients with ankylosing spondylitis (AS). The aim of
      this study was to develop a core set of recommendations to be given to patients
      by their rheumatologists. A systematic literature research of scientific and
      patient-oriented literature revealed 70 raw recommendations. These
      recommendations were evaluated and ranked at a meeting of the Ankylosing
      Spondylitis International Federation (ASIF, 26 participants including 19 patients
      with AS, 5 rheumatologists and 2 physiotherapists from 13 countries) in November
      2011. Thereafter, the 59 remaining recommendations were extensively discussed,
      supplemented, reworded, condensed and voted on during a meeting of local branch
      leaders of the AS patient organisation in Germany (Deutsche Vereinigung Morbus
      Bechterew, DVMB) with 80 participants (95 % of whom with AS), 2 rheumatologists
      and 1 occupational therapist in March 2012. The core set of final recommendations
      comprises (1) a general statement regarding living with AS which was considered
      highly important by patients and (2) the following domains: sitting position,
      walking, sleeping, at work, exercises, sports and recreational activities, diet
      and lifestyle, sexuality and pregnancy, fall prevention, car driving and
      advantages of membership in an AS-specific patient organisation. Most
      recommendations are relevant already in early disease, others concern advanced AS
      (e.g. fall prevention and car driving). The selected recommendations received
      high agreements (80-100 %). A first core set of recommendations for the behaviour
      and environmental adaptations of patients with AS was established under
      participation of many patients.

PMID- 23539273
TI  - The Organization of Words and Symbolic Gestures in 18-Month-Olds' Lexicons:
      Evidence from a Disambiguation Task.
AB  - Infants' early communicative repertoires include both words and symbolic
      gestures. The current study examined the extent to which infants organize words
      and gestures in a single unified lexicon. As a window into lexical organization,
      eighteen-month-olds' (N = 32) avoidance of word-gesture overlap was examined and
      compared to avoidance of word-word overlap. The current study revealed that when
      presented with novel words, infants avoided lexical overlap, mapping novel words
      onto novel objects. In contrast, when presented with novel gestures, infants
      sought overlap, mapping novel gestures onto familiar objects. The results suggest
      that infants do not treat words and gestures as equivalent lexical items and that
      during a period of development when word and symbolic gesture processing share
      many similarities, important differences also exist between these two symbolic
      forms.

PMID- 23539274
TI  - [Integrated care in pain therapy: innovations and coordinated treatment offers
      from the "Techniker Krankenkasse"].
AB  - Sectorally segregated healthcare structures are seen as a major reason for
      deficits in quality and efficiency. With the introduction of SS 140 a ff. SGB V,
      the sectoral splitting into outpatient, inpatient and rehabilitative services
      will be eliminated. This is especially true for the requirements of state-of-the
      art multidisciplinary and comprehensive pain therapy. Through this form of
      contract competition and competition for the best idea, incentives shall be
      created for economic behaviour of market participants, above all the efficient
      use of limited resources and allocation of healthcare resources based on need.
      Selective contracts are essential competition parameters for continued innovative
      development of the healthcare system. They enable statutory healthcare providers
      to offer their insurants innovative treatments which are not available in
      standard care. Agreements can be made concerning higher levels of quality and
      healthcare services, incentives for economical behaviour and success-based
      payment models. The key idea is the orientation on the needs of the insurant. The
      successful realisation of innovation in pain therapy is described using a
      practical example. Professional contractual partners, high quality information
      and communication, the taking over of responsibility for treatment and cost
      effectiveness are factors essential the success of innovative treatment concepts.

PMID- 23539275
TI  - [Pain management in patients with cancer. Perspectives of various network
      participants].
AB  - BACKGROUND: High healthcare needs are evident for pain caused by cancer. Those
      affected are not only looking for help in acute inpatient structures but also for
      a much larger part in outpatient care structures. To avoid mistreatment,
      undertreatment or overtreatment of pain in people with cancer, it is necessary to
      differentiate the tasks and roles of different providers while highlighting the
      specific aspects of pain management within the given network structures.
      MATERIALS AND METHODS: Aspects, such as pain assessment and the necessary scope
      of action in pain treatment are illustrated from the perspective of nurses from
      home care services, primary physicians as well as the general or special
      ambulatory palliative care (AAPV or SAPV) on the basis of initial survey results
      and a documentation analysis. RESULTS: Ambulatory care nurses (93 %) and primary
      caregivers (64 %) use pain assessment scales. The kind of scales used varies. The
      ability to provide adequate pain care for patients in the immediate care
      situation is reported as given by more than half of the nurses (56.6 %).
      CONCLUSIONS: In order to ensure an adequate pain therapy targeted
      interprofessional coordination is required between outpatient and primary
      physicians with respect to aspects of pain assessment, scope of action and
      accessibility.

PMID- 23539276
TI  - [Intersectoral pain treatment. The Algesiologikum group].
AB  - Cross-sectoral clinical pathways for chronic pain patients in standard and
      routine care are a major challenge for the German healthcare system. The
      Algesiologikum group has developed such clinical pathways including an essential
      infrastructure. Cooperation partners of the Algesiologikum group are two
      outpatient medical care units, one neurosurgery practice and four hospitals. In
      the outpatient sector as well as in the inpatient sector the Algesiologikum group
      provides a multidisciplinary team caring for chronic pain patients. The range of
      treatment in the hospitals includes multimodal, invasive and surgical pain
      therapy. The present report illustrates possibilities and frontiers of the
      Algesiologikum concept based on all patients treated since 2009.

PMID- 23539277
TI  - [Prolonged-release tapentadol for phantom pain. A case series].
AB  - OBJECTIVES: The successful therapy of phantom pain remains a major challenge,
      because the underlying pathophysiological mechanisms are still not fully
      understood. A therapeutic approach with tapentadol has not been described so far.
      PATIENTS AND METHODS: Five patients suffering upper and lower extremity phantom
      pain were successfully treated with tapentadol (prolonged release) with differing
      doses. RESULTS: In 4 patients, a strongly reduced pain intensity between 4 and
      6.5 on the visual analog scale (VAS) was recorded. The fifth patient reported an
      increase in the nocturnal sleep duration from 2 to 5 h and a decrease in the
      number of phantom pain attacks by 30 %. In 2 patients, the additional medication
      could be lowered or stretched. Side effects (vertigo, fatigue) were only observed
      in one subject. CONCLUSION: The cases described provide preliminary evidence that
      the synergistic combination of MU-opioid receptor agonism (MOR) and noradrenalin
      re-uptake inhibition (NRI) provided by tapentadol may be beneficial in the
      treatment of phantom pain.

PMID- 23539278
TI  - [Schwannoma of the femoral nerve: a rare differential diagnosis of leg pain].
AB  - BACKGROUND: Schwannomas (neurinomas) are among the most frequent peripheral nerve
      tumors. Nevertheless, these are seldom located in the lower extremities in
      association with the femoral nerve. CLINICAL PRESENTATION: In this case, the
      occurrence of a schwannoma adjacent to the femoral nerve is described in a
      patient presenting with nonspecific pain in the thigh accompanied by a palpable
      mass. Sensory and motor deficits were not present. Further examinations by MRI
      and biopsy followed by histopathology, revealed the diagnosis of a schwannoma.
      The tumor was completely excised. CONCLUSION: Although schwannomas of the lower
      extremities are rare, they should be included in the differential diagnosis.
      Knowing the typical clinical symptoms, radiological signs, and histopathological
      findings, diagnosis should be straight forward.

PMID- 23539279
TI  - A comment on Craig et al.: ''Retigabine for the adjunctive treatment of adults
      with partial-onset seizures in epilepsy with and without secondary
      generalization: a NICE single technology appraisal''.

PMID- 23539281
TI  - Physician decision making for colorectal cancer screening in the elderly.
AB  - BACKGROUND: Although individualized decision making is recommended to
      appropriately screen for colorectal cancer (CRC) in older adults, it is unclear
      whether physicians solicit input from older patients before making a
      recommendation for or against CRC screening. OBJECTIVE: The purpose of this study
      was to examine whether physicians elect to engage older patients in
      individualized decision making for CRC screening. DESIGN AND PARTICIPANTS: We
      surveyed a random sample of 650 US primary care physicians by mail. Physicians
      responded to questions about three clinical vignettes involving 80-year-old
      female patients in good, fair, and poor health. We examined whether physicians
      reported that they would initiate a discussion with the patients about CRC
      screening and whether they would make a recommendation about screening or seek
      patient input first. RESULTS: A total of 276 eligible physicians responded (52 %
      corrected response rate). Whether physicians indicated they would initiate a
      discussion about CRC screening varied by vignette: 91 % of physicians indicated
      they would do so for the patient in good health and 66 % and 44 % for the
      patients in fair and poor health, respectively (p<0.0001). The proportion of
      physicians that would seek patient input for their screening recommendation also
      varied by vignette (45 % for good, 49 % for fair, and 26 % for poor). CONCLUSION:
      We found that physicians often individualize their CRC screening recommendations
      for older women by electing to engage patients in discussions and seeking their
      input before making a CRC recommendation. Physicians were more likely to elect to
      engage the patients represented by the good and fair health vignette, where the
      potential benefits likely outweigh the potential harms, than the patient in poor
      health, where the potential harms likely outweigh the potential benefits.

PMID- 23539280
TI  - Mutations in the TIR1 auxin receptor that increase affinity for auxin/indole-3
      acetic acid proteins result in auxin hypersensitivity.
AB  - The phytohormone auxin regulates virtually every aspect of plant development. The
      hormone directly mediates the interaction between the two members of the auxin
      coreceptor complex, a TRANSPORT INHIBITOR RESPONSE (TIR1)/AUXIN SIGNALING F-BOX
      protein and an AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressor. To
      learn more about the interaction between these proteins, a mutant screen was
      performed using the yeast (Saccharomyces cerevisiae) two-hybrid system in
      Arabidopsis (Arabidopsis thaliana). Two tir1 mutations were identified that
      increased interaction with Aux/IAAs. The D170E and M473L mutations increase
      affinity between TIR1 and the degron motif of Aux/IAAs and enhance the activity
      of the SCF(TIR1) complex. This resulted in faster degradation of Aux/IAAs and
      increased transcription of auxin-responsive genes in the plant. Plants carrying
      the pTIR1:tir1 D170E/M473L-Myc transgene exhibit diverse developmental defects
      during plant growth and display an auxin-hypersensitive phenotype. This work
      demonstrates that changes in the leucine-rich repeat domain of the TIR1 auxin
      coreceptor can alter the properties of SCF(TIR1).

PMID- 23539282
TI  - Predictors of CT colonography utilization among asymptomatic medicare
      beneficiaries.
AB  - BACKGROUND: Although the Centers for Medicare and Medicaid Services (CMS) denied
      coverage for screening computed tomography colonography (CTC) in March 2009,
      little is understood about whether CTC was targeted to the appropriate patient
      population prior to this decision. OBJECTIVE: Evaluate patient characteristics
      and known relative clinical indications for screening CTC among patients who
      received CTC compared to optical colonoscopy (OC). DESIGN/PARTICIPANTS: Cross
      sectional study of all 10,538 asymptomatic Medicare beneficiaries who underwent
      CTC between January 2007 and December 2008, compared to a cohort of 160,113
      asymptomatic beneficiaries who underwent OC, matched on county of residence and
      year of examination. MAIN MEASURES: Patient characteristics and known relative
      appropriate and inappropriate clinical indications for screening CTC. KEY
      RESULTS: CTC utilization was higher among women, patients > 65 years of age,
      white patients, and those with household income > 75 % (p = 0.001). Patients with
      relatively appropriate clinical indications for screening CTC were more likely to
      undergo CTC than OC including presumed incomplete OC (OR 80.7, 95 % CI 76.01
      85.63); sedation risk (OR 1.11, 95 % CI 1.05-1.17); and chronic anticoagulation
      risk (OR 1.46, 95 % CI 1.38-1.54), after adjusting for patient characteristics
      and known clinical indications. Conversely, patients undergoing high-risk
      screening, an inappropriate indication, were less likely to receive CTC (OR 0.4,
      95 % CI 0.37-0.42). Overall, 83 % of asymptomatic patients referred to CTC had at
      least one clinical indication relatively appropriate for CTC (8,772/10,538).
      CONCLUSION: During the 2 years preceding CMS denial for screening, CTC was
      targeted to asymptomatic patients with relatively appropriate clinical
      indications for CTC/not receiving OC. However, CTC utilization was lower among
      certain demographic groups, including minority patients. These findings raise the
      possibility that future coverage of screening CTC might exacerbate disparities in
      colorectal cancer screening while increasing overall screening rates.

PMID- 23539283
TI  - The patient centered medical home: mental models and practice culture driving the
      transformation process.
AB  - BACKGROUND: The Patient-Centered Medical Home (PCMH) has become a dominant model
      of primary care re-design. The PCMH model is a departure from more traditional
      models of healthcare delivery and requires significant transformation to be
      realized. OBJECTIVE: To describe factors shaping mental models and practice
      culture driving the PCMH transformation process in a large multi-payer PCMH
      demonstration project. DESIGN: Individual interviews were conducted at 17 primary
      care practices in South Eastern Pennsylvania. PARTICIPANTS: A total of 118
      individual interviews were conducted with clinicians (N = 47), patient educators
      (N = 4), office administrators (N = 12), medical assistants (N = 26), front
      office staff (N = 7), nurses (N = 4), care managers (N = 11), social workers (N =
      4), and other stakeholders (N = 3). A multi-disciplinary research team used a
      grounded theory approach to develop the key constructs describing factors shaping
      successful practice transformation. KEY RESULTS: Three central themes emerged
      from the data related to changes in practice culture and mental models necessary
      for PCMH practice transformation: 1) shifting practice perspectives towards
      proactive, population-oriented care based in practice-patient partnerships; 2)
      creating a culture of self-examination; and 3) challenges to developing new roles
      within the practice through distribution of responsibilities and team-based care.
      The most tension in shifting the required mental models was displayed between
      clinician and medical assistant participants, revealing significant barriers
      towards moving away from clinician-centric care. CONCLUSIONS: Key factors driving
      the PCMH transformation process require shifting mental models at the individual
      level and culture change at the practice level. Transformation is based upon
      structural and process changes that support orientation of practice mental models
      towards perceptions of population health, self-assessment, and the development of
      shared decision-making. Staff buy-in to the new roles and responsibilities
      driving PCMH transformation was described as central to making sustainable change
      at the practice level; however, key barriers related to clinician autonomy
      appeared to interfere with the formation of team-based care.

PMID- 23539284
TI  - Medicare part D prescription drug program: benefits, unintended consequences and
      impact on health disparities.

PMID- 23539285
TI  - Direct-to-consumer television advertising: time to turn off the tube?

PMID- 23539286
TI  - Choice, Degree of Preference, and Happiness Indices with Persons with
      Intellectual Disabilities: A Surprising Finding.
AB  - Two persons with severe intellectual disabilities and two persons with profound
      intellectual disabilities were repeatedly presented with five different pairs of
      food items. The five pairs of items represented different degrees of preference,
      from highest to lowest. Happiness indices were monitored from the time that a
      pair of items was presented until a choice was made. Surprisingly, participants
      showed very few happiness indices throughout the study, and degree of preference
      had very little effect on frequency of happiness indices. Questions are raised
      regarding choice opportunities and indices of happiness as indicators of quality
      of life.

PMID- 23539287
TI  - PotD protein stimulates biofilm formation by Escherichia coli.
AB  - In natural environments bacteria often adopt a biofilm-growth mode. PotD is a
      spermidine/putrescine-binding periplasmic protein belonging to polyamine
      transport system and we have examined its role during biofilm formation and for
      planktonic growth in Escherichia coli BL21(DE3) strains that either over-express
      PotD (PotD+), or under-express it (PotDi) and also in a control strain with
      vector pET26b(+) (PotD0). The three strains displayed similar growth in
      planktonic growth-mode, but over expression of PotD protein greatly stimulated
      the formation of biofilms, while less biofilm formed by strain PotDi in
      comparison to strain PotD0. The expressions of five genes, recA, sfiA, groEL,
      groES, and gyrA, were increasingly expressed in PotD+ biofilm cells. Thus, PotD
      is likely to change the rate of polyamine synthesis, which stimulates the
      expression of SOS genes and biofilm formation.

PMID- 23539288
TI  - Predicting Optimal Preference Assessment Methods for Individuals with
      Developmental Disabilities.
AB  - The single-stimulus (SS) preference assessment procedure has been described as
      more appropriate than the paired stimulus (PS) procedure for "lower functioning"
      individuals, but this guideline's vagueness limits its usefulness. We
      administered the SS and PS preference assessment procedures with food items to
      seven individuals with severe or profound developmental disabilities who scored
      at level 2 of the Assessment of Basic Learning Abilities (ABLA) and seven who
      scored at ABLA level 3. Thirteen of the 14 participants also received these
      assessments (PS and SS), with non-food items. The two procedures were about
      equally effective for both groups, and with both types of stimuli, although the
      PS procedure produced more refined preference hierarchies. Most participants
      showed moderate to high correlations in preference scores between the two
      procedures for both food and non-food items. These results suggest that, for
      individuals who score at either ABLA level 2 or ABLA level 3, the SS and the PS
      procedures are equally likely to identify preferred stimuli.

PMID- 23539289
TI  - Sox10-dependent neural crest origin of olfactory microvillous neurons in
      zebrafish.
AB  - The sense of smell in vertebrates is detected by specialized sensory neurons
      derived from the peripheral nervous system. Classically, it has been presumed
      that the olfactory placode forms all olfactory sensory neurons. In contrast, we
      show that the cranial neural crest is the primary source of microvillous sensory
      neurons within the olfactory epithelium of zebrafish embryos. Using
      photoconversion-based fate mapping and live cell tracking coupled with laser
      ablation, we followed neural crest precursors as they migrated from the neural
      tube to the nasal cavity. A subset that coexpressed Sox10 protein and a
      neurogenin1 reporter ingressed into the olfactory epithelium and differentiated
      into microvillous sensory neurons. Timed loss-of-function analysis revealed a
      critical role for Sox10 in microvillous neurogenesis. Taken together, these
      findings directly demonstrate a heretofore unknown contribution of the cranial
      neural crest to olfactory sensory neurons in zebrafish and provide important
      insights into the assembly of the nascent olfactory system.
      DOI:http://dx.doi.org/10.7554/eLife.00336.001.

PMID- 23539290
TI  - Endogenous jasmonic and salicylic acids levels in the Cd-hyperaccumulator Noccaea
      (Thlaspi) praecox exposed to fungal infection and/or mechanical stress.
AB  - KEY MESSAGE: Sensitivity to Erysiphe in Noccaea praecox with low metal supply is
      related to the failure in enhancing SA. Cadmium protects against fungal-infection
      by direct toxicity and/or enhanced fungal-induced JA signaling. Metal-based
      defense against biotic stress is an attractive hypothesis on evolutionary
      advantages of plant metal hyperaccumulation. Metals may compensate for a defect
      in biotic stress signaling in hyperaccumulators (metal-therapy) by either or both
      direct toxicity to pathogens and by metal-induced alternative signaling pathways.
      Jasmonic acid (JA) and salicylic acid (SA) are well-established components of
      stress signaling pathways. However, few studies evaluate the influence of metals
      on endogenous concentrations of these defense-related hormones. Even less data
      are available for metal hyperaccumulators. To further test the metal-therapy
      hypothesis we analyzed endogenous SA and JA concentrations in Noccaea praecox, a
      cadmium (Cd) hyperaccumulator. Plants treated or not with Cd, were exposed to
      mechanical wounding, expected to enhance JA signaling, and/or to infection by
      biotrophic fungus Erysiphe cruciferarum for triggering SA. JA and SA were
      analyzed in leaf extracts using LC-ESI(-)-MS/MS. Plants without Cd were more
      susceptible to fungal attack than plants receiving Cd. Cadmium alone tended to
      increase leaf SA but not JA. Either or both fungal attack and mechanical wounding
      decreased SA levels and enhanced JA in the Cd-rich leaves of plants exposed to
      Cd. High leaf Cd in N. praecox seems to hamper biotic-stress-induced SA, while
      triggering JA signaling in response to fungal attack and wounding. To the best of
      our knowledge, this is the first report on the endogenous JA and SA levels in a
      Cd-hyperaccumulator exposed to different biotic and abiotic stresses. Our results
      support the view of a defect in SA stress signaling in Cd hyperaccumulating N.
      praecox.

PMID- 23539291
TI  - Advanced view factor analysis method for radiation exchange.
AB  - A raster-based method for determining complex view factor patterns is presented
      (HURES model). The model uses Johnson and Watson's view factor analysis method
      for fisheye lens photographs. The entire sphere is divided into 13 different view
      factors: open sky; sunny and shaded building walls, vegetation (trees) and ground
      surfaces above and below 1.2 m from the ground surface. The HURES model gave
      reasonable view factor results in tests at two urban study sites on summer days:
      downtown Nanaimo, B.C., Canada and Changwon, Republic of Korea. HURES gave better
      estimates of open sky view factors determined from fisheye lens photographs than
      did ENVI-met 3.1 and RayMan Pro. However, all three models underestimated sky
      view factor. For view factor analysis in outdoor urban areas, the 10 degrees 
      interval of rotation angle at 100 m distance of annuli will be suitable settings
      for three-dimensional computer simulations. The HURES model can be used for the
      rapid determination of complex view factor patterns which facilitates the
      analysis of their effects. Examples of how differing view factor patterns can
      affect human thermal sensation indices are given. The greater proportion of sunny
      view factors increased the computed predicted mean vote (PMV) by 1.3 on the sunny
      side of the street compared with the shady side during mid-morning in downtown
      Nanaimo. In another example, effects of differing amounts of open sky, sunny
      ground, sunny buildings and vegetation combined to produce only slight
      differences in PMV and two other human thermal sensation indices, PET and UTCI. 

PMID- 23539292
TI  - Cloning, expression, and characterization of TNFSF14 (LIGHT) gene in mefugu,
      Takifugu obscurus.
AB  - LIGHT/TNFSF14 is a member of the tumor necrosis factor ligand superfamily, which
      plays important roles in inflammatory and immune responses. In this study, the
      cDNA of mefugu (Takifugu obscures) LIGHT (designated as fLIGHT) was amplified
      from spleen by reverse transcription polymerase chain reaction. The open reading
      frame of fLIGHT covers 765 bp and translates into a 254-aa protein. The predicted
      three-dimensional (3D) structure of the soluble LIGHT of mefugu (designated as
      fsLIGHT) monomer analyzed by comparative protein modeling revealed that it was
      very similar to its human counterpart. Real-time quantitative PCR analysis
      indicated that LIGHT is constitutively expressed in various tissues in mefugu.
      The soluble LIGHT binding of green fluorescent protein (GFP) (designated as
      GFP/fsLIGHT) had been cloned into the pET28a vector; SDS-PAGE and western
      blotting analysis confirmed that the recombinant protein pET28a-GFP/fsLIGHT was
      efficiently expressed in Escherichia coli BL21 (DE3). After purification, the
      GFP/fsLIGHT fusion protein obtained similar fluorescence spectrum to those of
      GFP. Laser scanning confocal microscopy analysis showed GFP/fsLIGHT could bind to
      its receptors. In view of our basic research, LIGHT may be a potential
      immunologic factor for enhancing immunological efficacy in fish, and our results
      might provide a platform for further study into the effects of LIGHT.

PMID- 23539293
TI  - Microfabricated Microelectrode Sensor for Measuring Background and Slowly
      Changing Dopamine Concentrations.
AB  - The electrochemical detection of neurotransmitters in vivo has centered on fast
      scan cyclic voltammetry (FSCV) due to its temporal resolution, sensitivity and
      chemical selectivity. FSCV is a differential technique that records phasic
      (second-to-second) changes in the concentration of electroactive
      neurotransmitters such as dopamine (DA). To isolate the currents due to
      fluctuations in analyte concentration, in other words to make these phasic
      measurements, requires the subtraction of a large background current. The
      subtraction of this background and its volatility renders FSCV unable to
      determine background or slowly varying concentrations of electroactive analytes.
      However, there is still a need to readily determine the background and slowly
      changing concentrations of electroactive analytes in tissue. For example, the
      background concentrations of DA vary throughout the brain and can affect the
      dynamics of dopaminergic systems. So, this report presents a microfabricated
      electrochemical sensor for measuring background and slowly changing
      concentrations of DA in vitro with the selectivity and sensitivity of FSCV. The
      sensor is comprised of two microfabricated microelectrodes which are spaced 8 MUm
      apart. Varying the applied potential of the outer electrode manipulates the local
      concentration of electroactive species including concentration at the inner
      electrode. These changes are measured at the inner electrode using FSCV. The
      resulting signal with calibration can determine the background and slowly
      changing concentration of DA with the selectivity and sensitivity of FSCV. In
      this study the background of DA is determined in vitro using this sensor. The DA
      signal is shown to be the result of adsorption/desorption at the outer electrode.
      Interference from ascorbate on the DA signal is shown to be minimal for this
      approach.

PMID- 23539294
TI  - XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single
      nucleotide polymorphisms in cervical cancer risk.
AB  - Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor
      lesions. Transformation may be induced by several mechanisms, including oncogene
      activation and genome instability. Individual differences in DNA damage
      recognition and repair have been hypothesized to influence cervical cancer risk.
      The aim of this study was to evaluate whether the double strand break gene
      polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H
      G>A (rs77381814) are associated to cervical cancer in Argentine women. A case
      control study consisting of 322 samples (205 cases and 117 controls) was carried
      out. HPV DNA detection was performed by PCR and genotyping of positive samples by
      EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by
      pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was
      OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no
      increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI
      = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6).
      Regarding XRCC3 R243H, the G allele was almost fixed in the population studied.
      In conclusion, although the sample size was modest, the present data indicate a
      statistical association between cervical cancer and XRCC2 R188H polymorphism.
      Future studies are needed to confirm these findings. 

PMID- 23539295
TI  - THE PHONOLOGICAL ORGANIZATION OF SIGN LANGUAGES.
AB  - Visually perceivable and movable parts of the body - the hands, facial features,
      head, and upper body - are the articulators of sign language. It is through these
      articulators that that words are formed, constrained, and contrasted with one
      another, and that prosody is conveyed. This article provides an overview of the
      way in which phonology is organized in the alternative modality of sign language.

PMID- 23539296
TI  - p38 Mitogen-activated protein kinase regulates nuclear receptor CAR that
      activates the CYP2B6 gene.
AB  - The constitutive active/androstane receptor (CAR) regulates hepatic drug
      metabolism by activating genes, such as cytochrome P450, and certain
      transferases. p38 Mitogen-activated protein kinase (MAPK) is highly activated in
      human primary hepatocytes but barely in human hepatoma cell lines including HepG2
      cells. Liganded-CAR induced CYP2B6 mRNA in human primary hepatocytes far more
      effectively than in HepG2 cells ectopically expressing CAR. In the present study,
      we found that activation of p38 MAPK by anisomycin potentiated induction of
      CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated
      human primary hepatocytes. siRNA knockdown of p38 MAPK abrogated the ability of
      anisomycin to synergistically induce CYP2B6 mRNA. In addition to CYP2B6,
      anisomycin cotreatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not
      CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs. Thus, activated p38 MAPK is
      required for liganded-CAR to selectively activate a set of genes that encode drug
      metabolizing enzymes. Our present results suggest that CAR-mediated induction of
      these enzymes cannot be understood by ligand binding alone because the
      specificity and magnitude of induction are codetermined by a given cell
      signaling, such as p38 MAPK; both physiologic and pathophysiological states of
      cell signaling may have a strong impact in hepatic drug-metabolizing capability
      during treatments.

PMID- 23539297
TI  - Melatonin and its contribution to tumor attenuation in systemic malignancies.

PMID- 23539298
TI  - EZH2 inhibition decreases p38 signaling and suppresses breast cancer motility and
      metastasis.
AB  - EZH2 is a Polycomb group protein that exerts oncogenic functions in breast
      cancer, where its overexpression is associated with metastatic disease. While it
      reportedly acts a transcriptional repressor through trimethylation of histone H3
      at lysine 27, EZH2 may exhibit context-dependent activating functions. Despite
      associations with worse outcome and metastasis in breast cancer, a functional
      role of EZH2 in breast cancer metastasis in vivo has not been demonstrated.
      Furthermore, whether EZH2 regulates cancer cell phenotype and motility are
      unknown. In this study, we discovered that knockdown of EZH2 induces a phenotypic
      reprogramming from mesenchymal to epithelial, reduces motility, and blocks
      invasion in breast cancer cell lines. In vivo, EZH2 downregulation in MDA-MB-231
      cells decreases spontaneous metastasis to the lungs. We uncover an unexpected
      role of EZH2 in inducing the p38 mitogen-activated protein kinase signaling
      pathway, an important regulator of breast cancer invasion and metastasis. In
      breast cancer cells, EZH2 binds to phosphorylated p38 (p-p38) in association with
      other core members of the Polycomb repressive complex 2, EED, and SUZ12, and EZH2
      overexpression leads to increased levels of p-p38 and of activated, downstream
      pathway proteins. The effect on p-p38 was confirmed in vivo, where it correlated
      with decreased spontaneous metastasis. In clinical specimens of matched primary
      and invasive breast carcinomas, we found that EZH2 expression was upregulated in
      100 % of the metastases, and that EZH2 and p-p38 were coexpressed in 63 % of
      cases, consistent with the functional results. Together our findings reveal a new
      mechanism by which EZH2 functions in breast cancer, and provide direct evidence
      that EZH2 inhibition reduces breast cancer metastasis in vivo.

PMID- 23539300
TI  - [Potentials and limitations of the planned compulsory quality assurance program
      for cataract surgery (Qesu)].
AB  - Cataract surgery is scheduled for a federal program for quality improvement
      across the different sectors of care (outpatient care and hospitals). In case of
      implementation not only ophthalmic surgeons but all ophthalmologists would have
      to contribute to the documentation. Urgency, potential benefits and limitations
      of a compulsory compared to a voluntary quality assessment system are analyzed.

PMID- 23539299
TI  - The Caenorhabditis elegans epidermis as a model skin. I: development, patterning,
      and growth.
AB  - The skin of the nematode Caenorhabditis elegans is composed of a simple epidermal
      epithelium and overlying cuticle. The skin encloses the animal and plays central
      roles in body morphology and physiology; its simplicity and accessibility make it
      a tractable genetic model for several aspects of skin biology. Epidermal
      precursors are specified by a hierarchy of transcriptional regulators. Epidermal
      cells form on the dorsal surface of the embryo and differentiate to form the
      epidermal primordium, which then spreads out in a process of epiboly to enclose
      internal tissues. Subsequent elongation of the embryo into a vermiform larva is
      driven by cell shape changes and cell fusions in the epidermis. Most epidermal
      cells fuse in mid-embryogenesis to form a small number of multinucleate syncytia.
      During mid-embryogenesis the epidermis also becomes intimately associated with
      underlying muscles, performing a tendon-like role in transmitting muscle force.
      Post-embryonic development of the epidermis involves growth by addition of new
      cells to the syncytia from stem cell-like epidermal seam cells and by an increase
      in cell size driven by endoreplication of the chromosomes in epidermal nuclei.

PMID- 23539301
TI  - Transgenic manipulation of plant embryo sacs tracked through cell-type-specific
      fluorescent markers: cell labeling, cell ablation, and adventitious embryos.
AB  - Expression datasets relating to the Arabidopsis female gametophyte have enabled
      the creation of a tool set which allows simultaneous visual tracking of each
      specific cell type (egg, synergids, central cell, and antipodals). This cell
      specific, fluorescent labeling tool-set functions from gametophyte
      cellularization through fertilization and early embryo development. Using this
      system, cell fates were tracked within Arabidopsis ovules following molecular
      manipulations, such as the ablation of the egg and/or synergids. Upon egg cell
      ablation, it was observed that a synergid can switch its developmental fate to
      become egg/embryo-like upon loss of the native egg. Also, manipulated was the
      fate of the somatic ovular cells, which can become egg- and embryo-like,
      reminiscent of adventitious embryony. These advances represent initial steps
      toward engineering synthetic apomixis resulting in seed derived wholly from the
      maternal plant. The end goal of applied apomixis research, fixing important
      agronomic traits such as hybrid vigor, would be a key benefit to agricultural
      productivity.

PMID- 23539302
TI  - Improved ancestry inference using weights from external reference panels.
AB  - MOTIVATION: Inference of ancestry using genetic data is motivated by applications
      in genetic association studies, population genetics and personal genomics. Here,
      we provide methods and software for improved ancestry inference using genome-wide
      single nucleotide polymorphism (SNP) weights from external reference panels. This
      approach makes it possible to leverage the rich ancestry information that is
      available from large external reference panels, without the administrative and
      computational complexities of re-analyzing the raw genotype data from the
      reference panel in subsequent studies. RESULTS: We extensively validate our
      approach in multiple African American, Latino American and European American
      datasets, making use of genome-wide SNP weights derived from large reference
      panels, including HapMap 3 populations and 6546 European Americans from the
      Framingham Heart Study. We show empirically that our approach provides much
      greater accuracy than either the prevailing ancestry-informative marker (AIM)
      approach or the analysis of genome-wide target genotypes without a reference
      panel. For example, in an independent set of 1636 European American genome-wide
      association study samples, we attained prediction accuracy (R(2)) of 1.000 and
      0.994 for the first two principal components using our method, compared with
      0.418 and 0.407 using 150 published AIMs or 0.955 and 0.003 by applying principal
      component analysis directly to the target samples. We finally show that the
      higher accuracy in inferring ancestry using our method leads to more effective
      correction for population stratification in association studies. AVAILABILITY:
      The SNPweights software is available online at
      http://www.hsph.harvard.edu/faculty/alkes-price/software/. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23539303
TI  - An accessible database for mouse and human whole transcriptome qPCR primers.
AB  - MOTIVATION: Real time quantitative polymerase chain reaction (qPCR) is an
      important tool in quantitative studies of DNA and RNA molecules; especially in
      transcriptome studies, where different primer combinations allow identification
      of specific transcripts such as splice variants or precursor messenger RNA.
      Several softwares that implement various rules for optimal primer design are
      available. Nevertheless, as designing qPCR primers needs to be done manually, the
      repeated task is tedious, time consuming and prone to errors. RESULTS: We used a
      set of rules to automatically design all possible exon-exon and intron-exon
      junctions in the human and mouse transcriptomes. The resulting database is
      included as a track in the UCSC genome browser, making it widely accessible and
      easy to use. AVAILABILITY: The database is available from the UCSC genome browser
      (http://genome.ucsc.edu/), track name 'Whole Transcriptome qPCR Primers' for the
      hg19 (Human) and mm10 (Mouse) genome versions. Batch query is available in the
      following:
      http://www.weizmann.ac.il/complex/compphys/software/Amit/primers/batch_query_qpcr
      primers.htm CONTACT: amit.zeisel@weizmann.ac.il or eytan.domany@weizmann.ac.il
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23539304
TI  - Density-based hierarchical clustering of pyro-sequences on a large scale--the
      case of fungal ITS1.
AB  - MOTIVATION: Analysis of millions of pyro-sequences is currently playing a crucial
      role in the advance of environmental microbiology. Taxonomy-independent, i.e.
      unsupervised, clustering of these sequences is essential for the definition of
      Operational Taxonomic Units. For this application, reproducibility and robustness
      should be the most sought after qualities, but have thus far largely been
      overlooked. RESULTS: More than 1 million hyper-variable internal transcribed
      spacer 1 (ITS1) sequences of fungal origin have been analyzed. The ITS1 sequences
      were first properly extracted from 454 reads using generalized profiles. Then,
      otupipe, cd-hit-454, ESPRIT-Tree and DBC454, a new algorithm presented here, were
      used to analyze the sequences. A numerical assay was developed to measure the
      reproducibility and robustness of these algorithms. DBC454 was the most robust,
      closely followed by ESPRIT-Tree. DBC454 features density-based hierarchical
      clustering, which complements the other methods by providing insights into the
      structure of the data. AVAILABILITY: An executable is freely available for non
      commercial users at ftp://ftp.vital-it.ch/tools/dbc454. It is designed to run
      under MPI on a cluster of 64-bit Linux machines running Red Hat 4.x, or on a
      multi-core OSX system. CONTACT: dbc454@vital-it.ch or nicolas.guex@isb-sib.ch.

PMID- 23539305
TI  - MCScanX-transposed: detecting transposed gene duplications based on multiple
      colinearity scans.
AB  - SUMMARY: Gene duplication occurs via different modes such as segmental and single
      gene duplications. Transposed gene duplication, a specific form of single-gene
      duplication, 'copies' a gene from an ancestral chromosomal location to a novel
      location. MCScanX is a toolkit for detection and evolutionary analysis of gene
      colinearity. We have developed MCScanX-transposed, a software package to detect
      transposed gene duplications that occurred within different epochs, based on
      execution of MCScanX within and between related genomes. MCScanX-transposed can
      be also used for integrative analysis of gene duplication modes for a genome and
      to annotate a gene family of interest with gene duplication modes. AVAILABILITY:
      MCScanX-transposed is freely available at
      http://chibba.pgml.uga.edu/mcscan2/transposed/ SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23539306
TI  - FishingCNV: a graphical software package for detecting rare copy number
      variations in exome-sequencing data.
AB  - SUMMARY: Rare copy number variations (CNVs) are frequent causes of genetic
      diseases. We developed a graphical software package based on a novel approach
      that can consistently identify CNVs of all types (homozygous deletions,
      heterozygous deletions, heterozygous duplications) from exome-sequencing data
      without the need of a paired control. The algorithm compares coverage depth in a
      test sample against a background distribution of control samples and uses
      principal component analysis to remove batch effects. It is user friendly and can
      be run on a personal computer. AVAILABILITY AND IMPLEMENTATION: The main scripts
      are implemented in R (2.15), and the GUI is created using Java 1.6. It can be run
      on all major operating systems. A non-GUI version for pipeline implementation is
      also available. The program is freely available online:
      https://sourceforge.net/projects/fishingcnv/ SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23539307
TI  - Embracing uncertainty as a path to competence: cultural safety, empathy, and
      alterity in clinical training.

PMID- 23539309
TI  - The effect of exercise on fitness and performance-based tests of function in
      intermittent claudication: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Exercise is a widely accepted treatment known to
      improve walking ability in persons with peripheral arterial disease (PAD);
      however, it has not been confirmed as to whether exercise improves fitness and
      performance-based function and, consequently, performance of activities of daily
      living (ADL). This systematic review aims to identify whether any mode of
      structured exercise improves physical fitness or performance-based tests of
      function and whether improvement in walking ability is related to an improvement
      in these outcomes. DATA SOURCES AND STUDY SELECTION: Eligible studies included
      randomized controlled trials (RCTs) using an exercise intervention for the
      treatment of intermittent claudication with fitness (including the 6-min walk
      (6MW), aerobic capacity, shuttle and muscle strength) tests and performance-based
      tests of function as the outcomes. STUDY APPRAISAL AND METHODS: Assessment of
      study quality was performed using a modified version of the Physiotherapy
      Evidence Database Scale (PEDro). Relative effect sizes, mean differences (MDs)
      and 95 % confidence intervals were calculated and adjusted via Hedges' bias
      corrected for small sample sizes. Regression analyses were performed to establish
      relationships between walking ability and fitness outcomes. RESULTS: Twenty-four
      RCTs met the inclusion criteria: 19 aerobic training interventions and 5
      progressive resistance training (PRT). In total 924 participants (71 % male) were
      studied; with few participants over 75 years of age and the mean ankle brachial
      index was mean +/- standard deviation (SD) 0.66 +/- 0.06. The most common outcome
      measured was aerobic capacity (52 % of trials), which improved by 8.3 % +/- 8.7 %
      on average. Although there were no significant relationships, up to 16 % of the
      variance in walking distances can be explained by changes in walking economy.
      Muscle strength was measured in only five trials, improving by 42 % +/- 74 % on
      average. There was a strong significant relationship between change in plantar
      flexor muscle strength and change in initial claudication time (r = 0.99; p =
      0.001) and absolute claudication time (r = 0.75; p = 0.05) measured on a
      treadmill across trials measuring this muscle group. The 6MW distance was
      measured in only 14 % of trials. Walking and PRT significantly improved 6MW
      initial claudication distance (MD range 52-129 m) and total walking distance (MD
      range 36-108 m) in studies that measured this outcome. Only one trial assessed
      performance-based tests of function, and they did not improve significantly.
      CONCLUSION: Although data are limited, there is a strong significant relationship
      between plantar flexor muscle strength and treadmill walking ability. More
      research is needed to assess improvements in walking economy at specific
      timepoints and whether this translates to improvements in claudication outcomes
      and measurements pertaining to muscle strength. Future trials should focus on
      interventions that improve lower limb muscle strength and assess muscle strength,
      power and endurance across a variety of lower extremity muscle groups in order to
      understand these relationships further. The 6MW, muscle strength and performance
      based tests of function such as chair stand, balance scale, stair climb and gait
      speed are understudied in PAD. Future trials should examine the effects of
      exercise on performance-based tests of function, which may predict actual ADL
      performance and incident disability.

PMID- 23539310
TI  - Prenylated indole diketopiperazine alkaloids from a mangrove rhizosphere soil
      derived fungus Aspergillus effuses H1-1.
AB  - One new prenylated indole diketopiperazine alkaloid, named dihydroneochinulin B
      (1), one known spiro-polyketide-diketopiperazine hybrid cryptoechinuline D (2)
      and three related known metabolites didehydroechinulin B (3), neoechinulin B (4)
      and auroglaucin (5) were isolated from the mangrove rhizosphere soil derived
      fungus, Aspergillus effuses H1-1. The structures were assigned by detailed
      spectroscopic analysis. The enantiomers of cryptoechinuline D (2) were separated
      to be (+)-cryptoechinuline D (2a) and (-)-cryptoechinuline D (2b) by chiral HPLC,
      and their absolute configurations were determined by ECD analysis. The cytotoxic
      effects of the compounds were preliminarily evaluated on P388, HL-60, BEL-7402
      and A-549 cell lines by SRB or MTT methods, and compounds 2, 2a and 3 showed
      significant activities. 

PMID- 23539311
TI  - Neurotoxic effects of berberine on long-term L-DOPA administration in 6
      hydroxydopamine-lesioned rat model of Parkinson's disease.
AB  - The effects of berberine on long-term administration of L-DOPA in 6
      hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) were
      investigated. Rat models of PD were prepared by 6-OHDA lesions in the ipsilateral
      sides, and then were treated with berberine (5 and 15 mg/kg) and/or L-DOPA (10
      mg/kg) once daily for 21 days. Treatments with either concentration of berberine
      (5 and 15 mg/kg) in 6-OHDA-lesioned groups decreased the numbers of tyrosine
      hydroxylase (TH)-immunopositive neurons in the substantia nigra and the levels of
      dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid (HVA) in the striatum as compared to 6-OHDA-lesioned groups. In addition,
      dopaminergic neuronal cell death of the ipsilateral sides in 6-OHDA-lesioned
      groups was attenuated by L-DOPA administration. However, both concentrations of
      berberine in 6-OHDA-lesioned groups treated with L-DOPA aggravated the numbers of
      TH-immunopositive neurons in the substantia nigra and the levels of dopamine,
      norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated
      with berberine. These results suggest that berberine leads to the degeneration of
      dopaminergic neuronal cells in the substantia nigra in the rat model of PD with
      chronic L-DOPA administration. Long-term L-DOPA therapy that may involve possibly
      neurotoxic isoquinoline agents including berberine should involve monitoring for
      adverse symptoms.

PMID- 23539308
TI  - High-intensity interval training, solutions to the programming puzzle: Part I:
      cardiopulmonary emphasis.
AB  - High-intensity interval training (HIT), in a variety of forms, is today one of
      the most effective means of improving cardiorespiratory and metabolic function
      and, in turn, the physical performance of athletes. HIT involves repeated short
      to-long bouts of rather high-intensity exercise interspersed with recovery
      periods. For team and racquet sport players, the inclusion of sprints and all-out
      efforts into HIT programmes has also been shown to be an effective practice. It
      is believed that an optimal stimulus to elicit both maximal cardiovascular and
      peripheral adaptations is one where athletes spend at least several minutes per
      session in their 'red zone,' which generally means reaching at least 90% of their
      maximal oxygen uptake (VO2max). While use of HIT is not the only approach to
      improve physiological parameters and performance, there has been a growth in
      interest by the sport science community for characterizing training protocols
      that allow athletes to maintain long periods of time above 90% of VO2max
      (T@VO2max). In addition to T@VO2max, other physiological variables should also be
      considered to fully characterize the training stimulus when programming HIT,
      including cardiovascular work, anaerobic glycolytic energy contribution and acute
      neuromuscular load and musculoskeletal strain. Prescription for HIT consists of
      the manipulation of up to nine variables, which include the work interval
      intensity and duration, relief interval intensity and duration, exercise
      modality, number of repetitions, number of series, as well as the between-series
      recovery duration and intensity. The manipulation of any of these variables can
      affect the acute physiological responses to HIT. This article is Part I of a
      subsequent II-part review and will discuss the different aspects of HIT
      programming, from work/relief interval manipulation to the selection of exercise
      mode, using different examples of training cycles from different sports, with
      continued reference to T@VO2max and cardiovascular responses. Additional
      programming and periodization considerations will also be discussed with respect
      to other variables such as anaerobic glycolytic system contribution (as inferred
      from blood lactate accumulation), neuromuscular load and musculoskeletal strain
      (Part II).

PMID- 23539312
TI  - Module-based complexity formation: periodic patterning in feathers and hairs.
AB  - Patterns describe order which emerges from homogeneity. Complex patterns on the
      integument are striking because of their visibility throughout an organism's
      lifespan. Periodic patterning is an effective design because the ensemble of hair
      or feather follicles (modules) allows the generation of complexity, including
      regional variations and cyclic regeneration, giving the skin appendages a new
      lease on life. Spatial patterns include the arrangements of feathers and hairs in
      specific number, size, and spacing.We explorehowa field of equivalent progenitor
      cells can generate periodically arranged modules based on genetic information,
      physical-chemical rules and developmental timing. Reconstitution experiments
      suggest a competitive equilibrium regulated by activators/inhibitors involving
      Turing reaction-diffusion. Temporal patterns result from oscillating stem cell
      activities within each module (microenvironment regulation), reflected as growth
      (anagen) and resting (telogen) phases during the cycling of feather and hair
      follicles. Stimulating modules with activators initiates the spread of
      regenerative hair waves, while global inhibitors outside each module
      (macroenvironment) prevent this. Different wave patterns can be simulated by
      cellular automata principles. Hormonal status and seasonal changes can modulate
      appendage phenotypes, leading to 'organ metamorphosis', with multiple ectodermal
      organ phenotypes generated from the same precursors. We discuss potential novel
      evolutionary steps using this module-based complexity in several amniote
      integument organs, exemplified by the spectacular peacock feather pattern. We
      thus explore the application of the acquired knowledge of patterning in tissue
      engineering. New hair follicles can be generated after wounding. Hairs and
      feathers can be reconstituted through self-organization of dissociated progenitor
      cells.

PMID- 23539314
TI  - Anti-inflammatory interventions and skeletal muscle injury: benefit or detriment?
AB  - Exercise, eccentric contractions, acute trauma, and disease are all causal
      mechanisms of skeletal muscle injury. After skeletal muscle is injured, it
      undergoes sequential phases of degeneration, inflammation, regeneration, and
      fibrosis. Events that occur in response to inflammation trigger regenerative
      processes. However, since inflammation causes pain, decreases skeletal muscle
      function, has a negative effect on performance, and contributes to fibrosis,
      which is one of the leading causes of delayed regeneration, the general practice
      has been to reduce inflammation. The problem with this approach is that
      preventing inflammation may hinder recovery. Current treatment options for
      inflammation are not necessarily effective and, in some cases, they may be
      unsafe. This review focuses on the question of whether the most beneficial course
      of treatment should be to block inflammation or if it is sensible to allow
      inflammatory processes to progress naturally. If blocking inflammation is
      perceived as a beneficial approach, it is not yet known at what time point during
      the inflammatory response it is most sensible to interfere. To address these
      issues, this review evaluates the effects of various anti-inflammatory agents on
      recovery processes in response to exercise-induced, traumatic, and disease
      associated models of skeletal muscle injury. A collective analysis such as this
      should lay the foundation for future work that systematically manipulates the
      inflammatory response to most effectively promote regeneration and functional
      recovery in injured skeletal muscle, while reducing the negative effects of
      inflammatory processes such as pain and fibrosis. 

PMID- 23539315
TI  - Pulmonary chemoreflex responses are potentiated by tumor necrosis factor-alpha in
      mice.
AB  - Inhalation of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory
      cytokine, induces airway hyperresponsiveness, and the underlying mechanism is not
      fully understood. Hypersensitivity of vagal bronchopulmonary C-fiber afferents is
      known to contribute to the airway hyperresponsiveness during an airway
      inflammatory reaction. Because activation of these afferents can elicit pulmonary
      chemoreflexes, this study was designed to determine if a pretreatment with TNF
      alpha induced airway inflammation and enhanced the pulmonary chemoreflex
      sensitivity in anesthetized mice; and if so, whether the effect was mediated
      through activation of either or both of the TNF receptors, p55 and p75. Our
      results showed that TNF-alpha instilled into the lung caused an increased
      sensitivity of pulmonary chemoreflex responses to various chemical stimulants of
      the vagal bronchopulmonary C-fiber afferents. The increased sensitivity was found
      24 h later, persisted at 48 h, and then gradually declined after several days.
      The TNF-alpha-induced airway hypersensitivity was accompanied by airway
      inflammation as shown by a striking elevation of the levels of eosinophils and
      neutrophils, several potent bronchoactive inflammatory mediators, and
      proinflammatory cytokines in the bronchoalveolar lavage fluid. Furthermore, the
      increase in pulmonary chemoreflex response caused by TNF-alpha was partially
      abrogated in both p55-null and p75-null mice, but completely abolished in p55/p75
      null mice. In conclusion, TNF-alpha pretreatment induced airway inflammation and
      a sustained elevation of pulmonary chemoreflex sensitivity, which was mediated
      through an activation of both types of TNF receptors.

PMID- 23539316
TI  - Characterization of the inflammatory and metabolic profile of adipose tissue in a
      mouse model of chronic hypoxia.
AB  - In both obesity and chronic obstructive pulmonary disease (COPD), altered oxygen
      tension in adipose tissue (AT) has been suggested to evoke AT dysfunction,
      subsequently contributing to metabolic complications. Studying the effects of
      chronic hypoxia on AT function will add to our understanding of the complex
      pathophysiology of alterations in AT inflammation, metabolism, and mass observed
      in both obesity and COPD. This study investigated the inflammatory and metabolic
      profile of AT after chronic hypoxia. Fifty-two-week-old C57Bl/6J mice were
      exposed to chronic hypoxia (8% O2) or normoxia for 21 days, after which AT and
      plasma were collected. Adipocyte size, AT gene expression of inflammatory and
      metabolic genes, AT macrophage density, and circulating adipokine concentrations
      were measured. Food intake and body weight decreased upon initiation of hypoxia.
      However, whereas food intake normalized after 10 days, lower body weight
      persisted. Chronic hypoxia markedly reduced AT mass and adipocyte size. AT
      macrophage density and expression of Emr1, Ccl2, Lep, and Tnf were decreased,
      whereas Serpine1 and Adipoq expression levels were increased after chronic
      hypoxia. Concomitantly, chronic hypoxia increased AT expression of regulators of
      oxidative metabolism and markers of mitochondrial function and lipolysis.
      Circulating IL-6 and PAI-1 concentrations were increased, and leptin
      concentration was decreased after chronic hypoxia. Chronic hypoxia is associated
      with decreased rather than increased AT inflammation, and markedly decreased fat
      mass and adipocyte size. Furthermore, our data indicate that chronic hypoxia is
      accompanied by significant alterations in AT metabolic gene expression, pointing
      toward an enhanced AT metabolic rate.

PMID- 23539317
TI  - Proximal pulmonary arterial obstruction decreases the time constant of the
      pulmonary circulation and increases right ventricular afterload.
AB  - The time constant of the pulmonary circulation, or product of pulmonary vascular
      resistance (PVR) and compliance (Ca), called the RC-time, has been reported to
      remain constant over a wide range of pressures, etiologies of pulmonary
      hypertension, and treatments. We wondered if increased wave reflection on
      proximal pulmonary vascular obstruction, like in operable chronic thromboembolic
      pulmonary hypertension, might also decrease the RC-time and thereby increase
      pulse pressure and right ventricular afterload. Pulmonary hypertension of
      variable severity was induced either by proximal obstruction (pulmonary arterial
      ensnarement) or distal obstruction (microembolism) eight anesthetized dogs.
      Pulmonary arterial pressures (Ppa) were measured with high-fidelity
      micromanometer-tipped catheters, and pulmonary flow with transonic technology.
      Pulmonary ensnarement increased mean Ppa, PVR, and characteristic impedance,
      decreased Ca and the RC-time (from 0.46 +/- 0.07 to 0.30 +/- 0.03 s), and
      increased the oscillatory component of hydraulic load (Wosc/Wtot) from 25 +/- 2
      to 29 +/- 2%. Pulmonary microembolism increased mean Ppa and PVR, with no
      significant change in Ca and characteristic impedance, increased RC-time from
      0.53 +/- 0.09 to 0.74 +/- 0.05 s, and decreased Wosc/Wtot from 26 +/- 2 to 13 +/-
      2%. Pulse pressure increased more after pulmonary ensnarement than after
      microembolism. Concomitant measurements with fluid-filled catheters showed the
      same functional differences between the two types of pulmonary hypertension,
      with, however, an underestimation of Wosc. We conclude that pulmonary
      hypertension caused by proximal vs. distal obstruction is associated with a
      decreased RC-time and increased pulsatile component of right ventricular
      hydraulic load.

PMID- 23539319
TI  - A platform for nursing research on spirituality and religiosity.

PMID- 23539318
TI  - Effects of prostaglandins and COX-inhibiting drugs on skeletal muscle adaptations
      to exercise.
AB  - It has been ~40 yr since the discovery that PGs are produced by exercising
      skeletal muscle and since the discovery that inhibition of PG synthesis is the
      mechanism of action of what are now known as cyclooxygenase (COX)-inhibiting
      drugs. Since that time, it has been established that PGs are made during and
      after aerobic and resistance exercise and have a potent paracrine and autocrine
      effect on muscle metabolism. Consequently, it has also been determined that
      orally consumed doses of COX inhibitors can profoundly influence muscle PG
      synthesis, muscle protein metabolism, and numerous other cellular processes that
      regulate muscle adaptations to exercise loading. Although data from acute human
      exercise studies, as well as animal and cell-culture data, would predict that
      regular consumption of a COX inhibitor during exercise training would dampen the
      typical muscle adaptations, the chronic data do not support this conjecture. From
      the studies in young and older individuals, lasting from 1.5 to 4 mo, no
      interfering effects of COX inhibitors on muscle adaptations to resistance
      exercise training have been noted. In fact, in older individuals, a substantial
      enhancement of muscle mass and strength has been observed. The collective
      findings of the PG/COX-pathway regulation of skeletal muscle responses and
      adaptations to exercise are compelling. Considering the discoveries in other
      areas of COX regulation of health and disease, there is certainly an interesting
      future of investigation in this re-emerging area, especially as it pertains to
      older individuals and the condition of sarcopenia, as well as exercise training
      and performance of individuals of all ages. 

PMID- 23539320
TI  - Computer-based intervention to enhance self-management of calcium and vitamin D
      intake in women.
AB  - Despite the growing prevalence of osteoporosis, many middle-age women do not
      engage in recommended bone health promotion behaviors. Based on the Integrated
      Theory of Health Behavior Change, an intervention was designed to increase the
      self-management behaviors of calcium and vitamin D intake by strengthening health
      beliefs and using self-regulation skills. In this repeated measures experimental
      study, a convenience sample of 148 healthy women between 40 and 60 were assigned
      to either the computer-based intervention group (CBIG) or usual care group (UCG).
      Measures of health beliefs and calcium and vitamin D intake were obtained at
      baseline, 8 and 14 weeks, and 6 months. An interaction effect was observed for
      self-efficacy and approached significance for goal congruence. The CBIG had
      higher level of calcium intake at 14 weeks than women in the UCG when analyzed
      using intention to treat. Self-efficacy predicted calcium intake. 

PMID- 23539321
TI  - Testing the applicability of the family management style framework to chinese
      families.
AB  - Family management is an important concept in caring for chronically ill children.
      The purpose of this study is to determine the applicability of the Family
      Management Style Framework for Chinese families with a child who has a chronic
      condition. The children ranged in age from 6 to 16 years. The structural equation
      modeling approach was utilized to examine the relationships among the contextual
      variables, the family management, the child, and the family functioning. A total
      of 538 caregivers from seven hospitals in China were included in this study. The
      final model adequately fitted the data. The predictor variables accounted for
      23%, 26%, 7.8%, and 12% of the variance in the easy and the challenging parts of
      family management and the child and family unit, respectively. These findings
      indicated that the framework is applicable to Chinese families. This result
      reinforces the importance of interventions designed to enable caregivers to
      improve family management. 

PMID- 23539322
TI  - Impact of Asha intervention on stigma among rural Indian women with AIDS.
AB  - Rural women living with HIV/AIDS (WLA) in India face multifarious challenges
      which affect access to antiretroviral regimens and management of HIV/AIDS. The
      purpose of this pilot study, using cluster randomization, is to compare the
      effectiveness of the Asha-Life (AL) intervention, delivered by HIV-trained
      village women, Asha (Accredited Social Health Activists), with a usual care group
      on reduction of internalized stigma and avoidant coping among 68 WLA in rural
      India over a 6-month period. The findings demonstrated that participation in the
      AL intervention was associated with significant reductions in internalized stigma
      and the use of avoidant coping strategies at follow-up. The findings of our study
      are promising in terms of the role rural village women (Asha) may play in
      reducing internalized stigma and avoidant coping in the lives of rural WLA in
      India. 

PMID- 23539323
TI  - Effective treatment of a steroid-induced femoral neck fracture nonunion with a
      once-weekly administration of teriparatide in a rheumatoid patient: a case
      report.
AB  - INTRODUCTION: Nonunion of femoral neck fractures frequently occurs in elderly
      patients. In patients with rheumatoid arthritis, reoperation rates after internal
      fixation of a displaced femoral neck fracture increase by up to 60 %. Revision
      surgery with arthroplasty is often preferred for nonunion of femoral neck
      fractures because there are few effective options for conservative treatment.
      Teriparatide (TPTD) is a human parathyroid hormone analog and the only anabolic
      drug for the treatment of severe osteoporosis. DISCUSSION: There are two types of
      treatment regimens using TPTD: a once-daily administration of recombinant type
      TPTD and a once-weekly administration of a chemically synthesized type. Although
      there have been some reports showing that the once-daily recombinant type TPTD
      was effective for nonunion treatment, the effect of a once-weekly administration
      of the chemically synthesized type of TPTD is unknown. This report shows the
      efficacy of the chemically synthesized TPTD for the treatment of femoral neck
      fracture nonunion in a patient with risk factors that include rheumatoid
      arthritis and steroid intake.

PMID- 23539324
TI  - Catalytic Y-tailed amphiphilic homopolymers - aqueous nanoreactors for high
      activity, low loading SCS pincer catalysts.
AB  - A new amphiphilic homopolymer bearing an SCS pincer palladium complex has been
      synthesized by reversible addition fragmentation chain transfer polymerization.
      The amphiphile has been shown to form spherical and worm-like micelles in water
      by cryogenic transmission electron microscopy and small angle neutron scattering.
      Segregation of reactive components within the palladium containing core results
      in increased catalytic activity of the pincer compound compared to small molecule
      analogues. This allows carbon-carbon bond forming reactions to be performed in
      water with reduced catalyst loadings and enhanced activity.

PMID- 23539325
TI  - Mapping the protective pathway of emotional intelligence in youth: From social
      cognition to smoking intentions.
AB  - The purpose of this study was to test perceptions of the social consequences of
      smoking as a mediator of the relationship between emotional intelligence (EI) and
      intentions to smoke cigarettes among youth. Upper elementary school students (N =
      255, Mage = 10.9 years, 49% male) completed measures of EI, verbal intelligence,
      smoking-related intentions, past behavior, and perceived social consequences.
      Mediation was tested using the Sobel test. Perceived social consequences was a
      marginally significant mediator of the impact of total EI on intentions to smoke
      (Z = 1.91, p = .057). Follow-up analyses showed that perceived social
      consequences significantly mediated the effect of 2 EI abilities on smoking
      intentions: using emotions (Z = 2.02, p = .043) and managing emotions (Z = 2.28,
      p = .023). The results indicate that the role of higher EI in deterring smoking
      among youth may be related to social processing ability (i.e., greater
      perceptions of the negative social consequences of smoking). These findings
      contribute to a growing body of research demonstrating that EI may reduce
      cigarette smoking among youth by influencing their social perceptions.

PMID- 23539326
TI  - Effects of fatty acid provision during severe hypoxia on routine and maximal
      performance of the in situ tilapia heart.
AB  - The ability to maintain stable cardiac function during environmental hypoxia
      exposure is crucial for hypoxia tolerance in animals and depends upon the
      maintenance of cardiac energy balance as well as the state of the heart's
      extracellular environment (e.g., availability of metabolic fuels). Hypoxic
      depression of plasma [non-esterified fatty acids] (NEFA), an important cardiac
      aerobic fuel, is a common response in many species of hypoxia-tolerant fishes,
      including tilapia. We tested the hypothesis that decreased plasma [NEFA] is
      important for maintaining stable cardiac function during and following hypoxia
      exposure, based on the premise that continued reliance upon cardiac fatty acid
      metabolism under such conditions could impair cardiac function. We examined the
      effect of severe hypoxia exposure (PO2 < 0.2 kPa) on routine and maximum
      performance of the in situ perfused tilapia heart under conditions of routine
      (400 MUmol L(-1)) and low (75 MUmol L(-1)) [palmitate], which mimicked the in
      vivo levels of plasma [NEFA] found in normoxic and hypoxic tilapia, respectively.
      Under both concentrations of palmitate, the in situ tilapia heart showed
      exceptional hypoxic performance as a result of a high maximum glycolytic
      potential, confirming our previous results using a perfusate without fatty acids.
      We additionally provide evidence suggesting that non-contractile ATP demand is
      depressed in tilapia heart during hypoxia exposure. Cardiac performance during
      and following severe hypoxia exposure was unaffected by the level of palmitate.
      Thus, we conclude that hypoxic depression of plasma [NEFA] in fishes does not
      play a role in cardiac hypoxia tolerance. 

PMID- 23539327
TI  - Staying cold through dinner: cold-climate bats rewarm with conspecifics but not
      sunset during hibernation.
AB  - For temperate endotherms (i.e., mammals and birds) energy costs are highest
      during winter but food availability is lowest and many mammals depend on
      hibernation as a result. Hibernation is made up of energy-saving torpor bouts
      [periods of controlled reduction in body temperature (T b)], which are
      interrupted by brief periodic arousals to normothermic T b. What triggers these
      arousals in free-ranging hibernators is not well understood. Some temperate bats
      with intermittent access to flying insects during winter synchronize arousals
      with sunset, which suggests that, in some species, feeding opportunities
      influence arousal timing. We tested whether hibernating bats from a cold climate
      without access to food during winter also maintain a circadian rhythm for
      arousals or whether cues from conspecifics in the same cluster are more
      important. We used temperature telemetry to monitor skin temperature (T sk) of
      free-ranging little brown bats (Myotis lucifugus) hibernating in central
      Manitoba, Canada, where temperatures from 22 October to 22 March were too cold
      for flying insects. We found no evidence bats synchronized arousals with
      photoperiod but they did arouse synchronously with other bats in the same
      cluster. Thus, in the northern part of their range where flying insects are
      almost never available during winter, little brown bats exhibit no circadian
      pattern to arousals. Warming synchronously with others could reduce the energetic
      costs of arousal for individuals or could reflect disturbance of torpid bats by
      cluster-mates. 

PMID- 23539328
TI  - Water-clear cell adenoma associated with primary hyperparathyroidism: report of a
      case.
AB  - We report a case of water-clear cell adenoma associated with primary
      hyperparathyroidism. A 59-year-old woman with a history of renal stones and bone
      fracture was referred for investigation of hypercalcemia and an elevated serum
      parathyroid hormone level. Skeletal X-rays showed osteopenia and ultrasound
      showed enlarged tumors in both sides of the inferior thyroid region. Computed
      tomography demonstrated a tumor in the posterior aspect of the left thyroid lobe
      but no lesion in the right aspect of the neck. Grossly, we found a 500 mg left
      lower parathyroid gland (PTG) and a 100 mg right lower PTG. Histologically, the
      left lower PTG comprised mainly water-clear cells (WCCs) containing numerous
      vacuoles. Chief cells were dispersed among the WCCs, but the right lower PTG
      showed normal parathyroid tissue. Several investigators have speculated that WCCs
      are derived from chief cells, and we diagnosed WCC adenoma. Following this case
      report, we review the relevant literature.

PMID- 23539329
TI  - Health Outcomes and Socio-Economic Status Among the Elderly in Gansu and Zhejiang
      Provinces, China: Evidence from the CHARLS Pilot.

PMID- 23539330
TI  - Crown years for non-invasive cardiovascular imaging (Part II): 40 years of
      nuclear cardiology.

PMID- 23539331
TI  - Microcirculatory function and left ventricular recovery after STEMI, exploring
      the hidden territories.

PMID- 23539333
TI  - Surface-Supported Hydrocarbon pi Radicals Show Kondo Behavior.
AB  - Stable hydrocarbon radicals are utilized as spin standards and prototype metal
      free molecular magnets able to withstand ambient conditions. Our study presents
      experimental results obtained with submolecular resolution by scanning tunneling
      microscopy and spectroscopy from monomers and dimers of stable hydrocarbon pi
      radicals adsorbed on the Au(111) surface at 7-50 K. We provide conclusive
      evidence of the preservation of the radical spin-1/2 state, aiming to establish
      alpha,gamma-bisdiphenylene-beta-phenylallyl (BDPA) on Au(111) as a novel Kondo
      system, where the impurity spin is localized in a metal-free pi molecular orbital
      of a neutral radical state in gas phase preserved on a metal support.

PMID- 23539332
TI  - Altruism in terminal cancer patients and rapid tissue donation program: does the
      theory apply?
AB  - Rapid tissue donation (RTD) is an advancing oncology research procedure for
      collecting tumors, metastases, and unaffected tissue 2-6 h after death.
      Researchers can better determine rates of progression, response to treatment, and
      polymorphic differences among patients. Cancer patients may inquire about
      posthumous body donation for research to offer a personal contribution to
      research; however, there are barriers to recruiting for an RTD program.
      Physicians must reassure the patient that their treatment options and quality of
      care will not be compromised due to participating in RTD. In this commentary we
      discuss how theories of altruism may explain cancer patients' desire to
      participate in an RTD program, the ethical concerns of health care professionals
      and patients and the use of altruism as a recruitment strategy. We offer
      recommendations for examining the cultural and ethical climate of the institution
      prior to initiating such a program such as examining the relationship of
      healthcare professionals and patients, identifying ethical concerns, and
      examining ways to promote acceptance and buy-in across professionals, patients,
      and families.

PMID- 23539334
TI  - International Comparisons in Health Economics: Evidence from Aging Studies.

PMID- 23539335
TI  - Informing patients and making decisions.

PMID- 23539336
TI  - Re: Choi et al. (2012) Ped Surg Int 28:1165-1169: outcomes following laparoscopic
      inguinal hernia repair in infants compared with older children.

PMID- 23539337
TI  - Inhibitors of bacterial tubulin target bacterial membranes in vivo.
AB  - FtsZ is a homolog of eukaryotic tubulin that is widely conserved among bacteria
      and coordinates the assembly of the cell division machinery. FtsZ plays a central
      role in cell replication and is a target of interest for antibiotic development.
      Several FtsZ inhibitors have been reported. We characterized the mechanism of
      these compounds in bacteria and found that many of them disrupt the localization
      of membrane-associated proteins, including FtsZ, by reducing the transmembrane
      potential or perturbing membrane permeability. We tested whether the reported
      phenotypes of a broad collection of FtsZ inhibitors disrupt the transmembrane
      potential in Bacillus subtilis strain 168. Using a combination of flow cytometry
      and microscopy, we found that zantrin Z1, cinnamaldehyde, totarol, sanguinarine,
      and viriditoxin decreased the B. subtilis transmembrane potential or perturbed
      membrane permeability, and influenced the localization of the membrane
      associated, division protein MinD. These studies demonstrate that small molecules
      that disrupt membrane function in bacterial cells produce phenotypes that are
      similar to the inhibition of proteins associated with membranes in vivo,
      including bacterial cytoskeleton homologs, such as FtsZ. The results provide a
      new dimension for consideration in the design and testing of inhibitors of
      bacterial targets that are membrane-associated and provide additional insight
      into the structural characteristics of antibiotics that disrupt the membrane.

PMID- 23539338
TI  - An adult with right aortic arch and dysphagia.

PMID- 23539339
TI  - Value of reserve pulse pressure in improving the risk stratification of patients
      with normal myocardial perfusion imaging.
AB  - AIMS: To evaluate the incremental prognostic value of reserve-pulse pressure
      (reserve-PP: exercise-PP minus rest-PP) to standard risk factors among patients
      with suspected coronary artery disease (CAD) but normal exercise myocardial
      perfusion imaging (MPI). METHODS AND RESULTS: We studied 4269 consecutive
      symptomatic patients without known CAD who were referred for exercise MPI but had
      normal MPI results (mean age 58 +/- 12 years, 56% females, 84% referred for
      evaluation of chest pain or dyspnoea, 95% with intermediate pretest likelihood of
      CAD). There were 202 deaths over 5.1 +/- 1.4 years of follow-up. Reserve-PP was
      abnormal (<44 mmHg increase in PP from rest) in 1894 patients (44%). Patients
      with an abnormal reserve-PP had a higher risk of death compared with patients
      with normal reserve-PP [hazard ratio (HR): 2.47, 95% CI, 1.8-3.3]. In
      multivariable models adjusting for age, sex, ejection fraction, medications,
      heart rate recovery, Duke treadmill score (DTS), and rest-PP, each 10 mmHg lower
      reserve-PP was associated with a 20.6% increase in risk-adjusted mortality
      (adjusted HR 0.83, 95% CI 0.76-0.91). Models incorporating reserve-PP
      significantly reclassified risk compared with models without these parameters
      (net reclassification index 14.3%, P = 0.0007; integrated discrimination index
      0.69, P = 0.01). CONCLUSION: In patients without a history of CAD and a normal
      MPI, an abnormal reserve-PP identified and reclassified those at higher risk of
      death independent of known risk factors and DTS.

PMID- 23539340
TI  - Heart failure with preserved and reduced ejection fraction: different risk
      profiles for different diseases.

PMID- 23539341
TI  - Metal-Templated Ligand Architectures for Trinuclear Chemistry: Tricopper
      Complexes and Their O2 Reactivity.
AB  - A trinucleating framework was assmbled by templation of a heptadentate ligand
      around yttrium and lanthanides. The generated complexes orient three sets of two
      or three N-donors each for binding additional metal centers. Addition of three
      equivalents of copper(I) leads to the formation of tricopper(I) species.
      Reactions with dioxygen at low temperatures generate species whose spectroscopic
      features are consistent with a MU3,MU3-dioxo-tricopper complex. Reactivity
      studies were performed with a variety of substrates. The dioxo-tricopper species
      deprotonates weak acids, undergoes oxygen atom transfer with one equivalent of
      triphenylphosphine to yield triphenylphosphine oxide, and abstracts two hydrogen
      atom equivalents from tetramethylpiperidine-N-hydroxide (TEMPO-H). Thiophenols
      reduce the oxygenated species to a CuI3 complex and liberate two equivalents of
      disulfide, consistent with a four-electron four-proton process.

PMID- 23539342
TI  - The true cost of gallstone disease.
AB  - INTRODUCTION: Gallstone related disease accounts for a large expenditure in the
      NHS. The aim of this study was to review the events and costs of the patient
      journey to treatment, and propose guidelines to provide an efficient streamlined
      service. PATIENTS AND METHODS: All cholecystectomies performed in one unit in
      2009 were reviewed. The cost of all investigations and procedures performed was
      obtained from the Department of Health website. The individual cost was
      calculated for each patient. Results were expressed as mean (+/-SD) and compared
      using ANOVA. RESULTS: 132 patients (31 male) were reviewed with an overall age
      was 45.3 years (+/-15.1). Overall cost from referral to discharge was L4697 (+/
      2007) per patient, ranging from L3406 to L12011. The largest proportion was
      contributed by surgery at L2849 (+/-414), followed by inpatient costs at L1527
      (+/-1322). Pre-operative outpatient consultations were L174 (+/-144),
      supplemented by at least one ultrasound (L81+/-29). Additional imaging was
      required for only a minority. All blood tests involved in overall care
      contributed little to the total at L27 (+/-26). Patients who initially presented
      as an inpatient had an overall larger cost (L6112+/-1888 vs. L5097+/-1607;
      p=0.004). This difference was largely due to inpatient costs (L2611+/-1629 vs.
      L1194+/-1009; p<0.0001) and not the cost of surgery (p=0.29). Patients who were
      imaged in primary care prior to referral also had a lower overall cost (L4636+/
      1343 vs. L5697+/-1804; p=0.0005). This was also due to inpatient costs (L1076+/
      876 vs. L1740+/-1459; p=0.004) and not the actual surgery costs (p=0.36). Only 39
      were reviewed post-operatively, adding L38+/-69 to the overall cohort costs.
      CONCLUSION: Emergency presentation and repeat admissions result in higher
      inpatient costs and should be avoided. Reduced delay to elective surgery through
      active participation by primary care needs to be encouraged.

PMID- 23539343
TI  - The effect of androgen on the retention of extinction memory after conditioned
      taste aversion in mice.
AB  - Conditioned taste aversion (CTA) induced by the application of a novel taste such
      as sodium saccharin (Sac) as the conditioned stimulus (CS) and a malaise-inducing
      agent as the unconditioned stimulus (US), results in acquisition of CTA memory to
      Sac. In contrast, CTA is extinguished by repeated presentations of the CS without
      the US, resulting in acquisition of the extinction memory. We examined the
      effects of androgenic hormones on acquisition and retention of extinction memory
      in mice. We gonadectomized sexually immature mice and continuously administered
      androgens to these animals. After sexual maturation, the mice underwent a
      conditioning period followed by an extinction period. Retrieval tests revealed
      that the androgen-treated group showed significantly greater retention of
      extinction memory than the non-treated group 5 weeks later, whereas such
      significant difference was not observed in acquisition of extinction memory.
      These results demonstrate the enhancing effect of androgens on retention of
      extinction memory.

PMID- 23539344
TI  - A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in
      combination with gemcitabine in patients with solid tumors.
AB  - INTRODUCTION: MSC1992371A is an aurora kinase inhibitor with potential antitumor
      activity. METHODS: This trial established the maximum tolerated dose (MTD) and
      dose-limiting toxicities (DLTs) of oral MSC1992371A given before or after
      gemcitabine (1,000 mg/m(2)) in a 21-day cycle in patients with advanced
      malignancies. In schedule 1 (n = 31), gemcitabine was administered on days 1 and
      8 followed by escalating doses of MSC1992371A on days 2 and 9. In schedule 2 (n =
      35), MSC1992371A was given on days 1 and 8 followed by gemcitabine on days 2 and
      9. Patients had a range of solid tumors, the most frequent of which was
      colorectal (n = 19). RESULTS: In both schedules, the 37 mg/m(2) dose level was
      defined as the MTD. The main DLT was grade 4 neutropenia. Adverse events
      consisted of neutropenia, thrombocytopenia, asthenia, fatigue, nausea, vomiting,
      anorexia, and diarrhea. Administration of MSC1992371A prior to gemcitabine had no
      effect on the metabolism or elimination of gemcitabine. Time to reach maximum
      plasma concentration and area under the plasma concentration-time curve for
      MSC1992371A increased proportionally with dose. Exploration of drug-target
      related and tumor biomarkers did not identify predictors of biologic activity or
      response. Two patients (1 with lung carcinoma and 1 with hepatocellular
      carcinoma) had durable partial responses in schedule 2, and 5 patients had stable
      disease (SD) lasting 6 - 14 months. CONCLUSION: Oral MSC1992371A can be
      administered at a MTD of 37 mg/m(2) in combination with the standard 1,000
      mg/m(2) dose of gemcitabine, but hematologic toxicity requires careful
      monitoring. Preliminary signs of efficacy were indicated by durable responses and
      SD.

PMID- 23539345
TI  - Liver fatty acid binding protein gene-ablation exacerbates weight gain in high
      fat fed female mice.
AB  - Loss of liver fatty acid binding protein (L-FABP) decreases long chain fatty acid
      uptake and oxidation in primary hepatocytes and in vivo. On this basis, L-FABP
      gene ablation would potentiate high-fat diet-induced weight gain and weight
      gain/energy intake. While this was indeed the case when L-FABP null (-/-) mice on
      the C57BL/6NCr background were pair-fed a high-fat diet, whether this would also
      be observed under high-fat diet fed ad libitum was not known. Therefore, this
      possibility was examined in female L-FABP (-/-) mice on the same background. L
      FABP (-/-) mice consumed equal amounts of defined high-fat or isocaloric control
      diets fed ad libitum. However, on the ad libitum-fed high-fat diet the L-FABP (-/
      ) mice exhibited: (1) decreased hepatic long chain fatty acid (LCFA) beta
      oxidation as indicated by lower serum beta-hydroxybutyrate level; (2) decreased
      hepatic protein levels of key enzymes mitochondrial (rate limiting carnitine
      palmitoyl acyltransferase A1, CPT1A; HMG-CoA synthase) and peroxisomal (acyl CoA
      oxidase 1, ACOX1) LCFA beta-oxidation; (3) increased fat tissue mass (FTM) and
      FTM/energy intake to the greatest extent; and (4) exacerbated body weight gain,
      weight gain/energy intake, liver weight, and liver weight/body weight to the
      greatest extent. Taken together, these findings showed that L-FABP gene-ablation
      exacerbated diet-induced weight gain and fat tissue mass gain in mice fed high
      fat diet ad libitum--consistent with the known biochemistry and cell biology of L
      FABP.

PMID- 23539347
TI  - Environmental assessment of waste management in Greenland: current practice and
      potential future developments.
AB  - The majority of the waste in Greenland is disposed of in open dumps or
      incinerated in simple small-scale incinerators. There are relatively few
      environmental regulations that control the emissions of leachate, landfill gas
      and/or flue gases from incineration. Only some scrap metal and hazardous waste
      are collected separately and exported to Europe. The impacts from the current
      waste management system were modelled from a life-cycle perspective using the LCA
      waste model EASEWASTE. Impacts with regard to global warming, acidification, etc.
      are small (a few hundred person-equivalents (PE) for a system serving 56 000
      inhabitants), but significant environmental loads are caused by air emissions
      from the incinerators and leachate from the landfills. Several alternative
      management scenarios were modelled and results show that increased use of
      incineration, full utilization of the heat production for district heating and
      separation of hazardous waste probably could improve Greenland's waste management
      system. Segregation of recyclable materials as paper, cardboard and biowaste will
      do little to environmentally improve the waste management system due to loss of
      energy recovery from incineration and the long transport of the recyclables to
      markets. Export of waste to Denmark for incineration at modern waste incinerators
      with advanced flue gas cleaning could also be considered as a means to achieve
      better environmental performance of the waste management system.

PMID- 23539346
TI  - Up-regulation of stearoyl-CoA desaturase 1 increases liver MUFA content in obese
      Zucker but not Goto-Kakizaki rats.
AB  - The Goto-Kakizaki (GK) rat is an animal model for spontaneous-onset, non-obese
      type 2 diabetes. Despite abundant evidence about disorders in metabolism, little
      information is available about fatty acid metabolism in the liver of GK rats.
      This study aimed to investigate the characteristics of the fatty acid profile,
      particularly MUFA, and the mechanism underlying the alterations in fatty acid
      profiles in the liver of GK rats. The activities of enzymes that participate in
      the biosynthesis of MUFA, expressions of genes encoding these enzymes, and the
      fatty acid profile in the liver were compared with those of obese Zucker (fa/fa)
      (ZF) rats, which are obese and non-diabetic. Stearoyl-CoA desaturase (SCD)
      activity and SCD1 gene expression were considerably up-regulated in GK rats, and
      these levels were largely comparable to those in ZF rats. However, the
      proportions and contents of oleic acid and palmitoleic acid were very low
      considering the highly elevated activity of SCD in the liver of GK rats, when
      compared with ZF rats. Palmitoyl-CoA chain elongation (PCE) activity and fatty
      acid elongase (Elovl6) gene expression were markedly up-regulated in ZF rats,
      whereas PCE activity was up-regulated much less and Elovl6 gene expression was
      unchanged in GK rats. These results suggest the possibility that up-regulation of
      gene expression of Elovl6 along with SCD1 is indispensable to elevate the
      proportions and contents of oleic acid in the liver.

PMID- 23539348
TI  - Using the Receptivity model to uncover 'urine blindness': perceptions on the re
      use of urine.
AB  - Population growth, climatic changes and over-exploitation of natural resources
      are at the basis of the world's food crisis, which counts almost one million
      people without sufficient food sustenance. These changes require novel
      environmental practices which are based on nutrient recovery and management in
      agriculture. This contribution analyses and discusses users' perceptions on re
      use of urine as fertilizer through the lenses of the Receptivity model. A search
      was performed on Scopus (as well as other web search engines) using the keywords:
      urine, nutrient recovery and sanitation. Results shows how questions related to
      awareness, association, acquisition and application of the environmental change
      can represent hurdles to novel models of nutrient recovery and the use of urine
      in agriculture. Examples of hurdles identified from the literature relate to poor
      understanding of potential for urine reuse, social stigma attached to using dry
      sanitation and applying urine in agriculture and poor operational knowledge of
      application of urine in agriculture. Conclusion relates to the illustration of
      implications of such challenges on the design of environmental interventions.

PMID- 23539350
TI  - Antitumor activity of PEGylated nanoliposomes containing crocin in mice bearing
      C26 colon carcinoma.
AB  - Crocin is a pharmacologically active component of Crocus sativus. It is an
      unusual water-soluble carotenoid responsible for the red color of saffron. In
      various studies, the anticancer effect of saffron and its constituents has been
      established. Polyethylene glycolated nanoliposomes with a size range up to 200 nm
      are suitable for encapsulation of cytotoxic drugs and can target tumors passively
      through the enhanced permeation and retention effect. The aim of this study was
      to develop a nanoliposomal formulation containing crocin with a higher
      therapeutic index for the treatment of cancer. Four formulations of polyethylene
      glycolated nanoliposomes containing 25 mg/ml crocin were prepared with
      hydrogenated soy phosphatidylcholine, cholesterol, and methoxy-polyethylene
      glycol (MW 2000)-distearoylphosphatidylcholine at different molar ratios by a
      solvent evaporation method plus extrusion. Then the liposomes were characterized
      for their size, zeta potential, crocin encapsulation, release properties, and in
      vitro cytotoxicity against C26 colon carcinoma cells. Based on in vitro results,
      the best formulation was selected for an in vivo study, and its antitumor
      activity was evaluated in BALB/c mice bearing C26 colon carcinoma. The IC50 of
      crocin itself against C26 colon carcinoma was 0.73 mM. The characterization of
      the best formulation was as follow: Z-average size: 127.6 +/- 1.5 nm;
      polydispersity index: 0.087 +/- 0.018; zeta potential: - 21.7 mV +/- 6.7; %
      encapsulation: 84.62 +/- 0.59; % release after 168 hours in RPMI 1640 containing
      30 % FBS: 16.26 +/- 0.01 %. Liposomal crocin at doses of 50 and 100 mg/kg
      significantly decreased tumor size and increased survival rate compared with PBS
      and crocin in buffer (100 mg/kg) groups. The results of this study indicated that
      liposomal encapsulation of crocin could increase its antitumorigenic activity.
      Thus, to obtain an optimal dose for use in humans, the formulation merits further
      investigation.

PMID- 23539351
TI  - Antidiabetic attributes of desert and steppic plants: a review.
AB  - The rapidly increasing incidence of diabetes mellitus is becoming a serious
      threat to mankind's health in all parts of the world. In fact, known cases
      reflect only part of the problem, as many diabetics, especially with type 2
      diabetes, are unaware of their disease, which initially shows no definitive
      symptoms. Despite the great efforts invested in diabetes research, its prevalence
      continues to grow, while current medications do not cover all of the symptoms and
      complications of the disease. The present review highlights a plethora of studies
      focusing on the antidiabetic properties of desert and semidesert (steppic)
      plants, many of them being used for centuries in traditional medicine by Bedouins
      living in the arid zones of the Middle East and also by ethnic groups in other
      arid and semiarid parts of the world. The review concludes in summarizing the
      work done on the subject and also in pointing to the yet existing gaps in
      diabetes research of desert and steppic plants, and suggests directions for
      future exploration.

PMID- 23539352
TI  - Phytotherapy and women's reproductive health: the Cameroonian perspective.
AB  - Approximately 80 % of the population in Africa use traditional medicinal plants
      to improve their state of health. The reason of such a wide use of medicinal
      plants has been mainly attributed to their accessibility and affordability.
      Expectation of little if any side effects, of a "natural" and therefore safe
      treatment regimen, as well as traditional beliefs additionally contribute to
      their popularity. Several of these plants are used by women to relieve problems
      related to their reproductive health, during or after their reproductive life,
      during pregnancy, or following parturition. The African pharmacopoeia thus
      provides plants used for preventing and/or treating gynecological infections,
      dysmenorrhea, irregular menstruations, oligomenorrhea or protracted menstruation,
      and infertility. Such plants may then be used as antimicrobians, emmenagogues, or
      as suppressors of uterine flow. African medicinal plants are also used during
      pregnancy for prenatal care, against fetal malposition or malpresentation,
      retained dead fetus, and against threatened abortion. Some others are used as
      anti-fertilizing drugs for birth control. Such plants may exert various
      activities, namely, anti-implantation or early abortifacient, anti-zygotic,
      blastocytotoxic, and anti-ovulatory effects. Some herbs could also act as sexual
      drive suppressors or as a post-coital contraceptive by reducing the fertility
      index. A number of these plants have already been subject to scientific
      investigations and many of their properties have been assessed as estrogenic,
      oxytocic, or anti-implantation. Taking into account the diversity of the African
      pharmacopoeia, we are still at an early stage in the phytochemical and
      pharmacological characterization of these medicinal plants that affect the female
      reproductive system, in order to determine, through in vitro and in vivo studies,
      their pharmacological properties and their active principles.

PMID- 23539353
TI  - Black yeast biota in the mangrove, in search of the origin of the lethargic crab
      disease (LCD).
AB  - Knowledge of natural ecology is essential for a better understanding of
      pathogenicity and opportunism in black yeast-like fungi. Although etiological
      agents of diseases caused by these fungi are supposed to originate from the
      environment, their isolation from nature is difficult. This is probably due to
      their oligotrophic nature, low competitive ability, and, overall, insufficient
      data on their natural habitat. We obtained environmental samples from mangrove
      areas where mortalities by lethargic crab disease (LCD) are reported and areas
      without disease recorded. Isolation of chaetothyrialean black yeasts and
      relatives was performed using a highly selective protocol. Species-specific
      primers were used to determine if these isolates represented Exophiala cancerae
      or Fonsecaea brasiliensis, two proven agents of LCD, in order to test hypotheses
      about the origin of the disease. Isolates, identified by morphology as Fonsecaea-
      or Exophiala-like, were tested specific diagnostic markers for the fungi
      associated with LCD. Although several black fungi were isolated, the main
      causative agent of the LCD, E. cancerae, was not found. Molecular markers for F.
      brasiliensis revealed 10 positive bands for isolates from biofilms on mangrove
      leaves, branches, and aerial roots, of which four were confirmed by ITS
      sequencing. The absence of E. cancerae in environmental samples suggests that the
      species is dependent on the crab, as a genuine pathogen, different from F.
      brasiliensis, which is probably not dependent on the host species, U. cordatus.
      However, we did not attempt isolation from the marine water, which may represent
      the pathway of dispersion of the black yeast species between neighbor mangroves.

PMID- 23539355
TI  - An explorative cost-effectiveness analysis of school-based screening for child
      anxiety using a decision analytic model.
AB  - Anxiety in children is highly frequent and causes severe dysfunction. Various
      studies have used screening procedures to identify high-anxious children and
      offer them indicated prevention, but the cost-effectiveness of these screening
      procedures in combination with a preventive intervention has never been examined.
      This study compared four potential strategies in relation to the prevention of
      child anxiety: (1) a one-time school-based screening which offers a child-focused
      intervention, (2) the screening and offering of a parent-focused intervention,
      (3) the screening and differentially offering a child- or parent-focused
      intervention, depending on whether or not the parents are anxious themselves, and
      (4) or doing nothing. An economic evaluation from a societal perspective (i.e.
      including direct healthcare costs, direct non-healthcare costs, indirect costs,
      and out-of-pocket costs), using a decision-analytic model. The model was based on
      the real-world 2-year participation rates of screening and intervention, and real
      world costs and effects of high- and median-anxious children (aged 8-12) from
      regular primary schools. Incremental cost-effectiveness ratios were calculated,
      and several secondary and one-way sensitivity analyses were performed. The
      strategy of doing nothing and the strategy of screening and differentially
      offering the child- or parent-focused intervention, depending on parental anxiety
      levels were both worthwhile, with the latter strategy costing relatively little
      extra money compared to doing nothing. In conclusion, some evidence for the cost
      effectiveness of screening and intervening was found. Screening and offering a
      parent-focused intervention to children of anxious parents, and a child-focused
      intervention to children of non-anxious parents, were found to be the most cost
      effective approach. 

PMID- 23539354
TI  - Species distribution and virulence factors of Candida spp. isolated from the oral
      cavity of kidney transplant recipients in Brazil.
AB  - Although yeasts belonging to the genus Candida are frequently seen as commensals
      in the oral cavity, they possess virulence attributes that contribute for
      pathogenicity. The aims of the present study were to study the prevalence of
      Candida spp. isolated from the oral cavity of renal transplant recipients and to
      analyze strains virulence factors. We isolated a total of 70 Candida strains from
      111 transplant recipients, and Candida albicans was the most prevalent species
      (82.86 %). Oral candidiasis was diagnosed in 14.4 % kidney transplant patients,
      while 11 isolates (15.7 %) corresponded to non-Candida albicans Candida (NCAC)
      species. C. albicans adhered to a higher extension than NCAC strains. Some
      isolates of Candida tropicalis were markedly adherent to human buccal epithelial
      cells and highly biofilm-forming strains. Regarding proteinase activity, Candida
      orthopsilosis was more proteolytic than Candida metapsilosis. Candida glabrata
      and Candida dubliniensis showed very low ability to form biofilm on polystyrene
      microtiter plates. We have demonstrated here diverse peculiarities of different
      Candida species regarding the ability to express virulence factors. This study
      will contribute for the understanding of the natural history and pathogenesis of
      yeasts belonging to the genus Candida in the oral cavity of patients who were
      submitted to kidney transplant and are under immunosuppressive therapies.

PMID- 23539356
TI  - Mid-term clinical outcome following endovascular therapy in patients with chronic
      aortic occlusion.
AB  - Although endovascular therapy (EVT) has been widely used for iliac lesions due to
      acceptable patency with stenting, EVT has not been established as primary
      treatment for aortic occlusion, partly because of uncertainty regarding long-term
      results. The purpose of this study was to investigate outcomes following EVT with
      stenting for chronic aortic occlusion. This study was a single-center
      retrospective analysis of a prospectively maintained database. Between September
      2005 and May 2012, twenty-four lesions from 25 patients with a clinical diagnosis
      of chronic aortic occlusion (mean age, 71 years; 80 % male) were treated with EVT
      with stenting. Kaplan-Meier estimators were used to determine the patency rates
      according to Society for Vascular Surgery criteria. In results, lesion type was
      Trans Atlantic Inter-Society Consensus D in all patients. Mean lesion length was
      145 mm. Initial success rate and procedural complication rate were 96 % (24/25)
      and 8 % (2/25), respectively. At 36 months, primary and secondary patency rates
      were 76 and 94 %, respectively. Restenosis was observed in 5 patients, all of
      whom underwent reintervention (four successful, one failure and intensity of
      medical treatment). EVT can be safely done in patients with chronic aortic
      occlusion. Procedural morbidity and mid-term durability were comparable to those
      of bypass surgery up to 3 years.

PMID- 23539357
TI  - Pyothorax-associated lymphoma: complete remission achieved by chemotherapy alone.
AB  - We present the case of a patient with malignant lymphoma resulting from chronic
      pyothorax after artificial pneumothorax for pulmonary tuberculosis. The 81-year
      old female patient had a medical history of artificial pneumothorax from left
      pulmonary tuberculosis when she was 23 years old and subsequent chronic
      pyothorax. She had become aware of pain in the left back from October 2008. Chest
      computed tomography revealed a tumor measuring 61 mm * 27 mm behind the left
      sixth and seventh ribs. After biopsy revealed pyothorax-associated lymphoma, 4
      courses of R-CHOP therapy were administered, leading to complete remission. No
      recurrences were noted during follow-up over a 4-year period after the initiation
      of therapy.

PMID- 23539359
TI  - Normal spirometry values in healthy elderly: the Rotterdam Study.
AB  - Although many different reference values for spirometry are available from
      various studies, the elderly are usually underrepresented. Therefore, our
      objective was to assess reference values in a sample of healthy participants from
      a prospective population-based cohort study, including a large proportion of
      elderly. We included spirometry measurements of healthy, never smokers, from the
      Rotterdam Study and excluded participants with respiratory symptoms or
      prescriptions for respiratory medication. Age- and height-specific curves for the
      5th (lower limit of normal) and the 50th (median) percentile of Forced Expiratory
      Volume in 1 s (FEV1), Forced Vital Capacity (FVC), and the ratio (FEV1/FVC) were
      calculated by quantile regression models. The group of healthy elderly study
      subjects consisted of 1,125 individuals, with a mean age of 68 years, ranging
      from 47 to 96 years of age. Sex stratified equations for the median and the lower
      limit of normal were calculated adjusted for age and height. In this study, we
      report age- and height-dependent reference limits for FEV1, FVC, and FEV1/FVC in
      a large population, and prediction equations for the lower limit of normal and
      median values for a sample containing a large proportion of healthy elderly.

PMID- 23539360
TI  - Nano-mechanical mapping of the interactions between surface-bound RC-LH1-PufX
      core complexes and cytochrome c 2 attached to an AFM probe.
AB  - Electron transfer pathways in photosynthesis involve interactions between
      membrane-bound complexes such as reaction centres with an extrinsic partner. In
      this study, the biological specificity of electron transfer between the reaction
      centre-light-harvesting 1-PufX complex and its extrinsic electron donor,
      cytochrome c 2, formed the basis for mapping the location of surface-attached RC
      LH1-PufX complexes using atomic force microscopy (AFM). This nano-mechanical
      mapping method used an AFM probe functionalised with cyt c 2 molecules to
      quantify the interaction forces involved, at the single-molecule level under
      native conditions. With surface-bound RC-His12-LH1-PufX complexes in the photo
      oxidised state, the mean interaction force with cyt c 2 is approximately 480 pN
      with an interaction frequency of around 66 %. The latter value lowered 5.5-fold
      when chemically reduced RC-His12-LH1-PufX complexes are imaged in the dark to
      abolish electron transfer from cyt c 2 to the RC. The correspondence between
      topographic and adhesion images recorded over the same area of the sample shows
      that affinity-based AFM methods are a useful tool when topology alone is
      insufficient for spatially locating proteins at the surface of photosynthetic
      membranes.

PMID- 23539358
TI  - The Caenorhabditis elegans epidermis as a model skin. II: differentiation and
      physiological roles.
AB  - The Caenorhabditis elegans epidermis forms one of the principal barrier epithelia
      of the animal. Differentiation of the epidermis begins in mid embryogenesis and
      involves apical-basal polarization of the cytoskeletal and secretory systems as
      well as cellular junction formation. Secretion of the external cuticle layers is
      one of the major developmental and physiological specializations of the epidermal
      epithelium. The four post-embryonic larval stages are separated by periodic
      moults, in which the epidermis generates a new cuticle with stage-specific
      characteristics. The differentiated epidermis also plays key roles in endocrine
      signaling, fat storage, and ionic homeostasis. The epidermis is intimately
      associated with the development and function of the nervous system, and may have
      glial-like roles in modulating neuronal function. The epidermis provides passive
      and active defenses against skin-penetrating pathogens and can repair small
      wounds. Finally, age-dependent deterioration of the epidermis is a prominent
      feature of aging and may affect organismal aging and lifespan.

PMID- 23539362
TI  - Rethinking the existence of a steady-state Deltapsi component of the proton
      motive force across plant thylakoid membranes.
AB  - Light-driven photosynthetic electron transport is coupled to the movement of
      protons from the chloroplast stroma to the thylakoid lumen. The resulting proton
      motive force that is generated is used to drive the conformational rotation of
      the transmembrane thylakoid ATPase enzyme which converts ADP (adenosine
      diphosphate) and Pi (inorganic phosphate) into ATP (adenosine triphosphate), the
      energy currency of the plant cell required for carbon fixation and other
      metabolic processes. According to Mitchell's chemiosmotic hypothesis, the proton
      motive force can be parsed into the transmembrane proton gradient (DeltapH) and
      the electric field gradient (Deltapsi), which are thermodynamically equivalent.
      In chloroplasts, the proton motive force has been suggested to be split almost
      equally between Deltapsi and DeltapH (Kramer et al., Photosynth Res 60:151-163,
      1999). One of the central pieces of evidence for this theory is the existence of
      a steady-state electrochromic shift (ECS) absorption signal detected ~515 nm in
      plant leaves during illumination. The interpretation of this signal is
      complicated, however, by a heavily overlapping absorption change ~535 nm
      associated with the formation of photoprotective energy dissipation (qE) during
      illumination. In this study, we present new evidence that dissects the
      overlapping contributions of the ECS and qE-related absorption changes in wild
      type Arabidopsis leaves using specific inhibitors of the DeltapH (nigericin) and
      Deltapsi (valinomycin) and separately using leaves of the Arabidopsis lut2npq1
      mutant that lacks qE. In both cases, our data show that no steady-state ECS
      signal persists in the light longer than ~60 s. The consequences of our
      observations for the suggesting parsing of steady-state thylakoid proton motive
      force between (DeltapH) and the electric field gradient (Deltapsi) are discussed.

PMID- 23539361
TI  - Physiological and molecular mechanisms of plant salt tolerance.
AB  - Salt tolerance is an important economic trait for crops growing in both irrigated
      fields and marginal lands. The plant kingdom contains plant species that possess
      highly distinctive capacities for salt tolerance as a result of evolutionary
      adaptation to their environments. Yet, the cellular mechanisms contributing to
      salt tolerance seem to be conserved to some extent in plants although some highly
      salt-tolerant plants have unique structures that can actively excrete salts. In
      this review, we begin by summarizing the research in Arabidopsis with a focus on
      the findings of three membrane transporters that are important for salt
      tolerance: SOS1, AtHKT1, and AtNHX1. We then review the recent studies in salt
      tolerance in crops and halophytes. Molecular and physiological mechanisms of salt
      tolerance in plants revealed by the studies in the model plant, crops, and
      halophytes are emphasized. Utilization of the Na(+) transporters to improve salt
      tolerance in plants is also summarized. Perspectives are provided at the end of
      this review.

PMID- 23539363
TI  - Traveling-wave Ion Mobility-Mass Spectrometry Reveals Additional Mechanistic
      Details in the Stabilization of Protein Complex Ions through Tuned Salt
      Additives.
AB  - Ion mobility-mass spectrometry is often applied to the structural elucidation of
      multiprotein assemblies in cases where X-ray crystallography or NMR experiments
      have proved challenging. Such applications are growing steadily as we continue to
      probe regions of the proteome that are less-accessible to such high-resolution
      structural biology tools. Since ion mobility measures protein structure in the
      absence of bulk solvent, strategies designed to more-broadly stabilize native
      like protein structures in the gas-phase would greatly enable the application of
      such measurements to challenging structural targets. Recently, we have begun
      investigating the ability of salt-based solution additives that remain bound to
      protein ions in the gas-phase to stabilize native-like protein structures. These
      experiments, which utilize collision induced unfolding and collision induced
      dissociation in a tandem mass spectrometry mode to measure protein stability,
      seek to develop a rank-order similar to the Hofmeister series that categorizes
      the general ability of different anions and cations to stabilize gas-phase
      protein structure. Here, we study magnesium chloride as a potential stabilizing
      additive for protein structures in vacuo, and find that the addition of this salt
      to solutions prior to nano-electrospray ionization dramatically enhances
      multiprotein complex structural stability in the gas-phase. Based on these
      experiments, we also refine the physical mechanism of cation-based protein
      complex ion stabilization by tracking the unfolding transitions experienced by
      cation-bound complexes. Upon comparison with unbound proteins, we find strong
      evidence that stabilizing cations act to tether protein complex structure. We
      conclude by putting the results reported here in context, and by projecting the
      future applications of this method.

PMID- 23539364
TI  - Gene evolution and functions of extracellular matrix proteins in teeth.
AB  - The extracellular matrix (ECM) not only provides physical support for tissues,
      but it is also critical for tissue development, homeostasis and disease. Over 300
      ECM molecules have been defined as comprising the "core matrisome" in mammals
      through the analysis of whole genome sequences. During tooth development, the
      structure and functions of the ECM dynamically change. In the early stages,
      basement membranes (BMs) separate two cell layers of the dental epithelium and
      the mesenchyme. Later in the differentiation stages, the BM layer is replaced
      with the enamel matrix and the dentin matrix, which are secreted by ameloblasts
      and odontoblasts, respectively. The enamel matrix genes and the dentin matrix
      genes are each clustered in two closed regions located on human chromosome 4
      (mouse chromosome 5), except for the gene coded for amelogenin, the major enamel
      matrix protein, which is located on the sex chromosomes. These genes for enamel
      and dentin matrix proteins are derived from a common ancestral gene, but as a
      result of evolution, they diverged in terms of their specific functions. These
      matrix proteins play important roles in cell adhesion, polarity, and
      differentiation and mineralization of enamel and dentin matrices. Mutations of
      these genes cause diseases such as odontogenesis imperfect (OI) and amelogenesis
      imperfect (AI). In this review, we discuss the recently defined terms matrisome
      and matrixome for ECMs, as well as focus on genes and functions of enamel and
      dentin matrix proteins.

PMID- 23539365
TI  - [A combined mediastinal and retroperitoneal cystic lymphangioma as a rare cause
      of recurrent pleural effusion].
AB  - We report on a 71-year-old female patient with spontaneous unilateral recurrent
      chylothoraces - at first glance with no apparent cause. After performing CT, MRI,
      lymphatic scintigraphy, and CT-guided biopsy, we were able to establish the
      diagnosis of a combined mediastinal and retroperitoneal cystic lymphangioma.
      Together with a review of the literature concerning cystic lymphangioma, we also
      discuss possible differential diagnoses of chylothoraces.

PMID- 23539366
TI  - Corticotropin-releasing factor receptor subtype 2 in human colonic mucosa: down
      regulation in ulcerative colitis.
AB  - AIM: To assess corticotropin-releasing factor receptor 2 (CRF2) expression in the
      colon of healthy subjects and patients with ulcerative colitis (UC). METHODS: We
      examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal
      biopsies from healthy subjects and patients with UC (active or disease in
      remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD)
      by reverse transcription-polymerase chain reaction and immunofluorescence.
      RESULTS: Gene expression of CRF2 was demonstrated in the normal human colonic
      biopsies, but not in the human colorectal adenocarcinoma cell line Caco2.
      Receptor protein localization showed immunoreactive CRF2 receptors in the lamina
      propria and in the epithelial cells of the distal/sigmoid biopsy samples.
      Interestingly, CRF2 immunoreactivity was no longer observed in epithelial cells
      of patients with mild-moderately active UC and disease in remission, while
      receptor protein expression did not change in the lamina propria. No differences
      in CRF2 expression profile were observed in distal/sigmoid intestinal biopsies
      from HIV infection and FBD patients, showing no signs of inflammation.
      CONCLUSION: The down-regulation of the CRF2 receptor in the distal/sigmoid
      biopsies of UC patients is indicative of change in CRF2 signalling associated
      with the process of inflammation.

PMID- 23539367
TI  - Assessment by meta-analysis of interferon-gamma for the diagnosis of tuberculous
      peritonitis.
AB  - AIM: To investigate the performance and diagnostic accuracy of interferon-gamma
      (IFN-gamma) for tuberculous peritonitis (TBP) by meta-analysis. METHODS: A
      systematic search of English language studies was performed. We searched the
      following electronic databases: MEDLINE, EMBASE, Web of Science, BIOSIS, LILACS
      and the Cochrane Library. The Standards for Reporting Diagnostic Accuracy
      initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were
      used to assess the methodological quality of the studies. Sensitivity,
      specificity, and other measures of the accuracy of IFN-gamma concentration in the
      diagnosis of peritoneal effusion were pooled using random-effects models.
      Receiver operating characteristic (ROC) curves were applied to summarize overall
      test performance. Two reviewers independently judged study eligibility while
      screening the citations. RESULTS: Six studies met the inclusion criteria. The
      average inter-rater agreement between the two reviewers for items in the quality
      checklist was 0.92. Analysis of IFN-gamma level for TBP diagnosis yielded a
      summary estimate: sensitivity, 0.93 (95%CI, 0.87-0.97); specificity, 0.99 (95%CI,
      0.97-1.00); positive likelihood ratio (PLR), 41.49 (95%CI, 18.80-91.55); negative
      likelihood ratio (NLR), 0.11 (95%CI, 0.06-0.19); and diagnostic odds ratio (DOR),
      678.02 (95%CI, 209.91-2190.09). chi(2) values of the sensitivity, specificity,
      PLR, NLR and DOR were 5.66 (P = 0.3407), 6.37 (P = 0.2715), 1.38 (P = 0.9265),
      5.46 (P = 0.3621) and 1.42 (P = 0.9220), respectively. The summary receiver ROC
      curve was positioned near the desirable upper left corner and the maximum joint
      sensitivity and specificity was 0.97. The area under the curve was 0.99. The
      evaluation of publication bias was not significant (P = 0.922). CONCLUSION: IFN
      gamma may be a sensitive and specific marker for the accurate diagnosis of TBP.
      The level of IFN-gamma may contribute to the accurate differentiation of
      tuberculosis (TB) ascites from non-TB ascites.

PMID- 23539369
TI  - Child and Adolescent Behavior Inventory (CABI): A New Instrument for
      Epidemiological Studies and Pre-Clinical Evaluation.
AB  - BACKGROUND: Some questionnaires have already been elaborated to collect
      information from parents of children and adolescents, both as preparation for
      clinical evaluation and for screening and epidemiological studies. Here a new
      questionnaire, the CABI, is proposed, and it is validated in a population of 8-10
      year-old children. Compared to existing questionnaires, the CABI has been
      organized so as to be of medium length, with items concerning the most
      significant symptoms indicated by the DSM-IV-TR for the pertinent disorders, and
      covering a wider range than existing instruments. There is no charge for its use.
      METHODS: The answers of the parents of 302 children in the last 3 years of
      primary school provided the normative data. A discriminant validation was done
      for internalizing and externalizing disorders and as a comparison with self
      administered anxiety and depression scales. Exploratory factor analysis and
      internal consistency were also performed. RESULTS: Distribution of scores on the
      main scales in the normal population shows positive skewness, with the most
      frequent score being zero. A highly discriminant capability was found in regard
      to the sample of children with internalizing and externalizing disorders, with
      high correlation with the self-administered anxiety and depression scales.
      CONCLUSION: The CABI appears to be capable, at least for 8-10 year-old children,
      of effectively discriminating those with pathological symptoms from those
      without. Compared with the widely- used CBCL, it has the advantages of a lower
      number of items, which should facilitate parental collaboration especially in
      epidemiological studies, and of being free of charge.

PMID- 23539370
TI  - Towards 'sepsis with optimal treatment': evaluating the sepsis care pathway in
      acute medicine and identifying scope for systems improvement.
AB  - Sepsis commonly presents to the acute medicine unit (AMU). Timely recognition and
      treatment can reduce the significant associated mortality, but United Kingdom
      AMUs and emergency departments are often inadequately equipped to manage sepsis
      with early-goal directed therapy. We conducted an observational study of 50
      consecutive patients admitted with severe sepsis. Demographic, physiological and
      microbiological data, and information about the provision and timing of care were
      collected in real time. Treatment fell below "surviving sepsis" targets with only
      28% of patients receiving sufficient fluid, and 64% receiving antibiotics within
      3 hours, associated with delays in seeing physicians; however despite this
      mortality was lower than the nationally quoted average (14% at 90 days).

PMID- 23539371
TI  - Assessing the performance of the four question abbreviated mental test in the
      acute geriatric setting.
AB  - BACKGROUND: NCognitive impairment is common amongst acute geriatric hospital
      admissions but detection is often poor and this is associated with worse
      outcomes. The four-question abbreviated mental test (AMT4) has previously been
      promoted nationally in the acute setting as a succinct assessment tool. However,
      a recent national dementia Commissioning for Quality and Innovation (CQUIN) goal
      recommends a single screening question followed by the tenquestion abbreviated
      mental test (AMT10). We aimed to evaluate the negative predictive value of the
      AMT4 within the acute setting by comparing it to three other validated tools.
      METHOD: We identified 100 acute medical admissions (>60 years old) with a
      negative AMT4 and administered the AMT10, six-item cognitive impairment test
      (6CIT) and confusion assessment method (CAM) within 24 hours of admission.
      RESULTS: Forty-six percent of the participants scored positively on at least one
      of the additional tests despite a negative AMT4. Forty-four patients had a
      positive 6CIT, 23 had a positive AMT10 and six had a positive CAM. Using the 6CIT
      as a diagnostic standard, tests of short-term memory had the greatest sensitivity
      and specificity for cognitive impairment. CONCLUSION: Nearly half of the
      participants had signs of cognitive impairment despite a negative AMT4.
      Consequently, there is a risk of under diagnosis with potentially serious
      consequences for morbidity and mortality. Tests of shortterm memory were strongly
      associated with cognitive impairment. We propose the addition of such a test in
      order to increase the sensitivity of the AMT4 without compromising its brevity
      and utility in the acute setting.

PMID- 23539368
TI  - LIN-12/Notch signaling instructs postsynaptic muscle arm development by
      regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans.
AB  - The diverse cell types and the precise synaptic connectivity between them are the
      cardinal features of the nervous system. Little is known about how cell fate
      diversification is linked to synaptic target choices. Here we investigate how
      presynaptic neurons select one type of muscles, vm2, as a synaptic target and
      form synapses on its dendritic spine-like muscle arms. We found that the Notch
      Delta pathway was required to distinguish target from non-target muscles. APX
      1/Delta acts in surrounding cells including the non-target vm1 to activate LIN
      12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the
      expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to
      promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in
      non-target vm1 muscle is sufficient to induce muscle arm extension from these
      cells. Therefore, the LIN-12/Notch signaling specifies target selection by
      selectively up-regulating guidance molecules and forming muscle arms in target
      cells. DOI:http://dx.doi.org/10.7554/eLife.00378.001.

PMID- 23539372
TI  - A young woman with HIV and hemiparesis.
AB  - Progressive Multifocal Leucoencephalopathy (PML) is a rare and invariably fatal
      neurological disease that is seen patients with untreated HIV infection and as a
      complication of immune suppression with agents such as natalizumab. With the
      increasing occurrence of HIV, it is important to consider this condition in the
      differential diagnosis of patients with neurological features. We present the
      case of a young woman with a long history of HIV infection who presented with
      neurological symptoms; recognition of this diagnosis enabled identification of
      her poor compliance with treatment. The investigation and treatment of this
      condition is discussed.

PMID- 23539373
TI  - Posterior reversible encephalopathy syndrome: 'a headache' on the AMU.
AB  - Headache and seizures are common presentations to the acute medical unit. We
      report a case of posterior reversible encephalopathy syndrome (PRES) in a 73-yr
      old woman with a history of uncontrolled hypertension who had recently
      discontinued one of her antihypertensive drugs; such cases are rare but pose a
      diagnostic challenge given the nonspecific nature of the clinical presentation.
      However, early diagnosis and treatment leads to full recovery in the majority of
      patients.

PMID- 23539374
TI  - Spinal epidural hematoma: an important stroke mimic.
AB  - Tissue plasminogen activator (tPA) is, on occasion, given to patients who do not
      suffer from acute cerebral ischemia. As the underlying conditions often mistaken
      for acute ischemic stroke tend to produce transient dysfunction, and are
      generally seen in individuals younger than stroke patients, the outcome of such
      mistaken treatment is generally benign. We will describe two elderly patients
      with acute hemiparesis caused by spinal epidural hematomas (SEDH), both of whom
      were initially considered candidates for tPA. The literature review and
      discussion will emphasize features allowing the distinction between these unusual
      hemiparetic presentations of SEDH and acute brain ischemia, and briefly review
      other cervical lesions that may rarely present with hemiparesis.

PMID- 23539375
TI  - Problem-based review: The patient with acute adrenal failure.
AB  - Acute adrenal crisis is an important condition to consider in any shocked patient
      presenting to the acute medical unit. This article aims to highlight the key
      aspects of initial management, focussing on the importance of rapid recognition
      and prompt initiation of steroid treatment.

PMID- 23539376
TI  - Problem-based review: The patient with acute heart failure.
AB  - Acute heart failure is a common and potentially life threatening presentation to
      hospitals in the U.K.. Acute physicians at the front door of the hospital will
      often be involved with the initial management of these patients. Despite its many
      underlying causes, certain general treatment principles exist. We present a
      typical clinical scenario followed by an overview of the pathophysiology and
      management of acute heart failure and cardiogenic pulmonary oedema. The aim is to
      cover a broad spectrum of therapies ranging from medical treatment up to invasive
      devices, thereby discussing the available options from the emergency department
      to the intensive care unit.

PMID- 23539377
TI  - Problem based review: The patient taking methadone.
AB  - Methadone maintenance treatment (MMT) is an effective therapy for opioid
      dependence; its use is based on a harm reduction philosophy and represents one of
      a range of treatment approaches for opioid-dependent individuals. The medical
      literature supports MMT as a well established and cost-effective treatment for
      opioid-dependence that allows a return-to-normal physiological, psychological and
      societal functioning. The effectiveness of MMT is enhanced by psycho-social
      interventions such as contingency management and addressing other co-existing
      health and social needs. MMT saves lives and reduces violent and non-violent
      crime, drug use and the transmission of HIV, hepatitis C and other communicable
      diseases. For some people, MMT may continue for life, while others may eventually
      be able to discontinue and remain abstinent. Methadone interacts with numerous
      drugs and prolongs the corrected QT interval (QTc) with risk of sudden cardiac
      death. It has a prolonged half-life and premature discharge of patients after
      methadone overdose may be fatal. Each patient must be assessed, treated and
      monitored on an individual basis. Successful outcomes through MMT require
      knowledge, experience, vigilance, and diligence on the part of the physician, the
      patient and all of those involved in treatment.

PMID- 23539378
TI  - Foundation programme impact on junior doctor personality and anxiety in Northern
      Ireland.
AB  - OBJECTIVES: The main objectives of this study were to assess personality traits
      and levels of anxiety in Foundation Year 2 (F2) doctors during the foundation
      doctor training programme in the Northern Ireland Deanery (NIMDTA). METHODS: A
      prospective survey-based study was conducted for all F2 doctors attending the
      mandatory generic skills programme at NIMDTA. Anxiety was measured using the
      State-Trait Anxiety Inventory (STAI) while personality was assessed using the
      IPIP-NEO questionnaire. These previously validated questionnaires were completed
      at the start and again at the end of the F2 year. RESULTS: 147 (M=65, F=82) and
      106 (M=55, F=51) F2 doctors completed questionnaires at both time points. STAI
      scores suggested a moderate level of anxiety amongst both male and female doctors
      at baseline and at the end of the academic year. There was no difference between
      gender for either parameter (Baseline-State: 34.0 vs. 36.0, p=0.48 and Trait:
      39.0 vs. 40.5, p=0.33) (End-State: 41.0 vs. 36.0, p=0.14 and Trait: 42.0 vs.
      40.5, p=0.78). IPIP-NEO scores for F2 doctors were consistently higher in the
      Accommodation (93.9 & 92.3) and Consolidation (88.8 & 87.6) personality factors
      and lower in the Neuroticism factor (66.3 & 65.9) at both assessment time-points.
      Female F2 doctors scored significantly higher in the accommodation factor at the
      end of the academic year when compared to their male counterparts (88.0 vs. 94.0,
      p<0.001). There was no difference between the genders for the other personality
      factors at the end of the year (p>0.09). CONCLUSION: This first cohort of F2
      doctors were exposed to many emerging changes in their training which did not
      appear to have any detrimental effect on their anxiety levels or personality
      profiles and suggests that junior doctors may not be affected by external
      influences or changing educational environments.

PMID- 23539380
TI  - Buckyballs.
AB  - Buckyballs represent a new and fascinating molecular allotropic form of carbon
      that has received a lot of attention by the chemical community during the last
      two decades. The unabating interest on this singular family of highly strained
      carbon spheres has allowed the establishing of the fundamental chemical
      reactivity of these carbon cages and, therefore, a huge variety of fullerene
      derivatives involving [60] and [70]fullerenes, higher fullerenes, and endohedral
      fullerenes have been prepared. Much less is known, however, of the chemistry of
      the uncommon non-IPR fullerenes which currently represent a scientific curiosity
      and which could pave the way to a range of new fullerenes. In this review on
      buckyballs we have mainly focused on the most recent and novel covalent chemistry
      of fullerenes involving metal catalysis and asymmetric synthesis, as well as on
      some of the most significant advances in supramolecular chemistry, namely H
      bonded fullerene assemblies and the search for efficient concave receptors for
      the convex surface of fullerenes. Furthermore, we have also described the recent
      advances in the macromolecular chemistry of fullerenes, that is, those polymer
      molecules endowed with fullerenes which have been classified according to their
      chemical structures. This review is completed with the study of endohedral
      fullerenes, a new family of fullerenes in which the carbon cage of the fullerene
      contains a metal, molecule, or metal complex in the inner cavity. The presence of
      these species affords new fullerenes with completely different properties and
      chemical reactivity, thus opening a new avenue in which a more precise control of
      the photophysical and redox properties of fullerenes is possible. The use of
      fullerenes for organic electronics, namely in photovoltaic applications and
      molecular wires, complements the study and highlights the interest in these
      carbon allotropes for realistic practical applications. We have pointed out the
      so-called non-IPR fullerenes - those that do not follow the isolated pentagon
      rule - as the most intriguing class of fullerenes which, up to now, have only
      shown the tip of the huge iceberg behind the examples reported in the literature.
      The number of possible non-IPR carbon cages is almost infinite and the near
      future will show us whether they will become a reality. 

PMID- 23539379
TI  - Relationship of femtosecond-picosecond dynamics to enzyme-catalyzed H-transfer.
AB  - At physiological temperatures, enzymes exhibit a broad spectrum of conformations,
      which interchange via thermally activated dynamics. These conformations are
      sampled differently in different complexes of the protein and its ligands, and
      the dynamics of exchange between these conformers depends on the mass of the
      group that is moving and the length scale of the motion, as well as restrictions
      imposed by the globular fold of the enzymatic complex. Many of these motions have
      been examined and their role in the enzyme function illuminated, yet most
      experimental tools applied so far have identified dynamics at time scales of
      seconds to nanoseconds, which are much slower than the time scale for H-transfer
      between two heavy atoms. This chemical conversion and other processes involving
      cleavage of covalent bonds occur on picosecond to femtosecond time scales, where
      slower processes mask both the kinetics and dynamics. Here we present a
      combination of kinetic and spectroscopic methods that may enable closer
      examination of the relationship between enzymatic C-H -> C transfer and the
      dynamics of the active site environment at the chemically relevant time scale.
      These methods include kinetic isotope effects and their temperature dependence,
      which are used to study the kinetic nature of the H-transfer, and 2D IR
      spectroscopy, which is used to study the dynamics of transition-state- and ground
      state-analog complexes. The combination of these tools is likely to provide a new
      approach to examine the protein dynamics that directly influence the chemical
      conversion catalyzed by enzymes. 

PMID- 23539381
TI  - Carbenes from ionic liquids.
AB  - In the last decade an explosive development has been observed in the fields of
      both ionic liquids (ILs) as potential chemically inert solvents with many
      possible technical applications, and N-heterocyclic carbenes (NHCs) as catalysts
      with superb performance. Since the cations of many ILs can be deprotonated by
      strong bases yielding NHCs, this two fields are inherently connected. It has only
      recently been recognized that some of the commonly used basic anions of the ILs
      (such as acetate) are able to deprotonate azolium cations. While the resulting
      NHC could clearly be observed in the vapor phase, in the liquid - where the
      mutual electrostatic interactions within the ion network stabilize the ion pairs 
      the neutral NHC cannot be detected by commonly used analytical techniques;
      however, from these ionic liquids NHCs can be trapped, e.g., by complex
      formation, or more importantly these ILs can be directly used as catalysts, since
      the NHC content is sufficiently large for these applications. Apart from
      imidazole-2-ylidenes, the formation of other highly reactive neutral species
      ("abnormal carbenes," 2-alkylideneimidazoles, pyridine-ylidenes or pyridinium
      ylides) is feasible in highly basic ionic liquids. The cross-fertilizing overlap
      between the two fields may provide access to a great advance in both areas, and
      we give an overview here on the results published so far, and also on the
      remaining possibilities and challenges in the concept of "carbenes from ionic
      liquids." 

PMID- 23539382
TI  - Chemotherapy of MMR-deficient colorectal cancer.
AB  - Colorectal cancer (CRC) continues to rank as the third most common cancer in
      Western society and the second leading cause of cancer death in North America.
      There are at least three distinct, and relatively discreet, molecular pathways
      associated with this disease: chromosomal instability (CIN), microsatellite
      instability (MSI) and the cytosine polyguanine island methylator phenotype.
      Defects in the DNA mismatch repair system (MMR) account for the MSI phenotype and
      genotype of about 15 % of CRC. Although high frequency MSI tumors have better
      stage independent prognosis compared to those with CIN, MMR deficient CRC appears
      to be resistant to fluorouracil based treatment, but sensitive to other
      therapeutic regimens. This review summarises current literature on differential
      chemosensitivity of MMR-deficient CRC. 

PMID- 23539383
TI  - Novel therapeutic strategies in adult acute lymphoblastic leukemia--a focus on
      emerging monoclonal antibodies.
AB  - The outcomes in adult B-cell acute lymphoblastic leukemia (ALL) remain inferior
      to those achieved in pediatric populations. Targeted therapy with monoclonal
      antibodies may improve outcomes in adult B-cell ALL without significant additive
      toxicity. Rituximab is the best known monoclonal antibody and is routinely used
      in combination chemo-immunotherapy for treatment of adult B-cell ALL and Burkitts
      leukemia. A number of other monoclonal antibodies are currently under
      investigation for treatment of adult B-cell ALL including unconjugated antibodies
      (eg., ofatumumab, alemtuzumab and epratuzumab), antibodies conjugated to
      cytotoxic agents (eg., inotuzumab ozogamycin and SAR3419), antibodies conjugated
      to toxins such Pseudomonas or Diptheria toxins (eg., BL22 and moxetumomab
      pasudotox), and T-cell engaging bi-specific antibodies that redirect cytotoxic T
      lymphocytes to lyse target ALL cells (eg., blinatumomab). In this article we
      review the therapeutic implications, current status and results of monoclonal
      antibody-based therapy in adult B-cell ALL.

PMID- 23539384
TI  - High times, low sats: diffuse pulmonary infiltrates associated with chronic
      synthetic cannabinoid use.
AB  - INTRODUCTION: In recent years, cases of severe adverse effects from recreational
      use of synthetic cannabinoids (SC) have established that these agents represent a
      novel toxicologic hazard. CASE REPORT: A 21-year-old male presenting as a
      vehicular trauma victim was noted with diffuse pulmonary infiltrates related to
      chronic inhalation of multiple synthetic cannabinoid-containing products. Chest
      imaging revealed bilateral, subacute lung infiltrates; histopathological analysis
      of bronchial and alveolar tissues revealed an inflammatory process. An extensive
      workup failed to identify infectious, malignant, autoimmune, or hematologic
      causes of the syndrome, and toxicological analysis of the blood and body fluids
      confirmed the presence of multiple synthetic cannabinoids and metabolites. The
      patient recovered after an 8-day ICU course, wherein he received antibiotics,
      steroids, and mechanical ventilation. DISCUSSION: This case contributes to the
      currently evolving knowledge about SC agents, adding a rarely described pulmonary
      complication to the growing list of adverse effects associated with these
      products.

PMID- 23539385
TI  - Detection of endoscopic and histological inflammation after an attack of colonic
      diverticulitis is associated with higher diverticulitis recurrence.
AB  - BACKGROUND & AIMS: Colonic diverticulitis shows a high recurrence rate, but the
      factors associated with such recurrence are still unknown. The aim of our study
      was to investigate the role of endoscopic and histological inflammation as
      predictors for the recurrence of diverticulitis. METHODS: One hundred and thirty
      patients suffering from Acute Uncomplicated Diverticulitis (AUD) (81 males, 49
      females, mean age 64.71 years, range 40-85) were prospectively assessed. All
      patients had AUD confirmed by computerized tomography (CT) and endoscopy.
      Clinical, endoscopic and histological follow-up was performed after 6, 12 and
      thereafter 24 months after diagnosis of AUD. RESULTS: Sixteen patients were lost
      to follow-up. Diverticulitis recurred in 18 patients (13.84%): 15 (13.15%)
      patients showed recurrence of AUD, whilst 3 (2.63%) showed recurrence of
      complicated diverticulitis. At the end of the follow-up period, endoscopic
      inflammation was still detected in 31 (27.67%) patients, and active histological
      inflammation in 41 patients (36.6 %). Only detection of endoscopic and of
      histological inflammation during the follow-up was a predictor of diverticulitis
      recurrence (Log rank test, p = 0.0004). CONCLUSIONS: Detection of endoscopic and
      histological inflammation after attack of AUD was identified as a predictor of
      diverticulitis recurrence.

PMID- 23539386
TI  - Comparison of Quantiferon-TB Gold versus tuberculin skin test for tuberculosis
      screening in inflammatory bowel disease patients.
AB  - BACKGROUND & AIM: Screening for latent tuberculosis (LTB) is recommended before
      starting anti-TNF-alpha therapy. We compared the performance of Quantiferon-TB
      Gold (QFT-G) with the tuberculin skin test (TST) for the screening of LTB in a
      population of inflammatory bowel disease (IBD) patients who were candidates for
      anti-TNF-alpha therapy. METHODS: Ninety-two IBD patients who were candidates for
      anti-TNF-alpha therapy were tested with QTF-G and TST. Concomitant therapy and
      laboratory parameters were recorded. RESULTS: One subject was vaccinated with
      Bacille Calmette Guerin (BCG), 76% of patients were on immunosuppressive therapy
      (IST), and all patients had a negative TB history and negative chest X-ray.
      Agreement between the two tests was observed in 89.2% of patients (79.4% +/+,
      9.8% -/-), QFT-G+/TST- was observed in 4.4% (4) patients, and QFT-G-/TST+ was
      observed in 5.5%, one of which was previously vaccinated. All disagreements were
      observed in patients on IST (14.3% in this group). The agreement analysis showed
      moderate strength among the patients (k=0.508), while the agreement was only fair
      in the subgroup of patients on IST (k=0.388). CONCLUSION: Given the high risk of
      LTB reactivation in patients subjected to anti-TNF-alpha therapy, our results
      suggest that in our population, with low TB rate and very low BCG vaccination
      rate, both tests could be employed.

PMID- 23539387
TI  - Use of quantitative serum HBsAg for optimization of therapy in chronic hepatitis
      B patients treated with pegylated interferon alfa-2a: a Romanian cohort study.
AB  - BACKGROUND & AIMS: The aim of the study was to assess the clinical utility of
      serum HBsAg quantification as a surrogate biomarker for the prediction of
      sustained virological response (SVR) in chronic hepatitis B (CHB) patients
      treated with Pegylated Interferon alfa-2a (Peg-IFN alpha-2a). METHODS: We
      performed a prospective cohort study which included 57 patients with CHB treated
      48 weeks with Peg-IFN alpha-2a and followed for another 24 weeks. HBsAg was
      quantified at the baseline, during treatment and at the end of follow-up. SVR was
      defined as HBV-DNA below 2,000 IU/ml at 24 weeks after the end of therapy.
      RESULTS: The majority of patients had HBeAg-negative CHB (68%, n=39). Positive
      predictive factors for SVR at baseline were low levels of HBsAg (3.72 log10
      IU/ml, p=0.032) and HBV-DNA (3.96 log10 IU/ml, p=0.035). During treatment,
      patients who achieved SVR showed a marked decrease in serum HBsAg in comparison
      with nonresponders (at week 48 mean decrease of 1.06 +/- 1.3 log10 IU/ml versus
      0.04 +/- 0.5 log10 UI/ml, p=0.005). On therapy, HBV-DNA reduction >= 2 log10
      IU/ml with any decrease of HBsAg level at week 12 had a positive predictive value
      (PPV) of 80% (95% CI: 51.91-95.43%) for SVR, while HBV-DNA decline < 2 log10
      IU/ml without any decline of HBsAg had a negative predictive value (NPV) of
      85.71% (95% CI: 42.23-97.63%) for SVR. CONCLUSIONS: HBsAg quantification combined
      with HBV-DNA assessment could become an early useful tool to optimize the
      management of CHB patients treated with Peg-IFN alpha-2a, according to response
      guided therapy.

PMID- 23539388
TI  - Endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy: to
      do or not to do?
AB  - BACKGROUND: Dual antiplatelet therapy has to be used for at least one month after
      placement of bare metal coronary stents and for a minimum of one year after
      placement of drug eluting stents. Because of the higher risk of bleeding,
      guidelines recommend cessation of clopidogrel seven days prior to high-risk
      endoscopic procedures and to delay elective surgery/endoscopy until dual
      antiplatelet therapy is ended. Premature cessation of clopidogrel however, may
      lead to catastrophic cardiovascular sequelae. METHODS: We searched the MEDLINE
      database, EMBASE, and the Cochrane Library for English-language literature up to
      October 2012 to identify clinical trials on the bleeding risk of gastrointestinal
      endoscopic procedures in patients on uninterrupted clopidogrel/dual antiplatelet
      therapy. RESULTS: Six studies (high-risk endoscopic procedures: 5, low-risk
      endoscopic procedures: 1) on this issue were identified through the literature
      search. A total of 1,245 endoscopic procedures were performed under clopidogrel.
      Thirteen bleeding complications occurred (1%). None of the patients required
      angiographic or surgical intervention and there were no long-term sequelae.
      CONCLUSION: To date, data published on this issue are scarce and of poor quality.
      Nevertheless, there is no evidence to support the recommendations of the current
      guidelines to stop clopidogrel for at least one week prior to high-risk
      endoscopic procedures. In this setting, the clinical decision making should take
      place on an individual basis.

PMID- 23539389
TI  - 5-Fluorouracil potentiates the anti-cancer effect of oxaliplatin on Colo320
      colorectal adenocarcinoma cells.
AB  - BACKGROUND & AIMS. The present study was designed to examine the combined effects
      of Oxaliplatin (OXA) and 5-Fluorouracil (5-FU) in the Colo320 cell line. METHODS.
      The antiproliferative effects were evaluated using the MTT assay, apoptosis by
      flow cytometry, and RT-PCR-array technology was used to determine the major
      effects of the two chemotherapeutic drugs upon the most important genes involved
      in apoptosis. RESULTS. The antiproliferative effects of the therapeutic agents,
      as individual therapy or combined, proved to be dose and time-dependent, with
      increased efficiency for the combined treatment. Flow cytometry data revealed
      increased apoptotic processes in the case of the combined treatment at 24 hours
      after administration. The RT-PCR-array data indicated that at 24 hours after OXA
      treatment, 49 genes were differentially expressed, of which 45 were up-regulated
      and 4 down-regulated. In the case of the 5-FU treatment, 35 genes were down
      regulated and 2 up regulated. In the combined treatment of 5-FU and OXA, 19 genes
      were up-regulated and 15 down-regulated. CONCLUSIONS. This study proved that drug
      resistance could be counteracted by combining OXA with 5-FU to form a tandem that
      is capable of reducing cell proliferation and to stimulate extrinsic apoptosis
      pathway by targeting death receptors on the cell surface.

PMID- 23539390
TI  - Assessment of diffusion-weighted MRI and 18F-fluoro-deoxyglucose PET/CT in
      monitoring early response to neoadjuvant chemotherapy in adenocarcinoma of the
      esophagogastric junction.
AB  - BACKGROUND & AIMS: To prospectively assess whether changes in apparent diffusion
      coefficient (ADC) values or standardized uptake value (SUV) changes in 18F
      fluorodeoxyglucose (FDG) PET correlate with treatment response under neoadjuvant
      chemotherapy in patients with locally advanced adenocarcinoma of the
      esophagogastric junction (AEG). METHODS: Fifteen patients (median age, 64 years)
      with histologically proven AEG type I and II received 1.5 Tesla MRI including
      "diffusion-weighted imaging" and FDG PET/CT before and 14 days after neoadjuvant
      EOX chemotherapy. The FDG uptake of the tumor was quantified by calculating the
      SUV in static PET scans. ADC values within the tumor tissue were quantitatively
      assessed using a region-of-interest analysis excluding necrotic areas. Early
      metabolic response was defined as a decrease in the SUV(mean) >/= 35% in FDG PET
      two weeks following the start of neoadjuvant chemotherapy, which had been
      reported to be predictive of histopathological response and survival. Concordance
      between ADC and SUV changes, differences at first examination and overall
      survival were assessed. RESULTS: The ADC within the AEG tumors was significantly
      lower than in normal esophagus and increased following neoadjuvant chemotherapy
      by 16.0 +/- 1.1% (p=0.007). Tumor glucose SUV decreased by 29.1 +/- 23.2%
      (p=0.002). Initial ADC and SUV were comparable in both groups (p=0.65, p=0.82).
      ADC increase and metabolic PET-response were concordant in 73.3% of all patients.
      The median overall survival was 757 days for PET-responders and 623 days for PET
      non-responders (p=0.138). CONCLUSION: The ADC increase in AEG tumors following
      chemotherapy is concordant in the majority of cases to PET-response, but not
      correlated to prognosis in this study.

PMID- 23539391
TI  - Long term outcome following surgical treatment for distal gastric cancer.
AB  - BACKGROUND. At the current time, the belief that total gastrectomy (TG) offers a
      better survival benefit compared with distal gastrectomy (DG) in distal gastric
      cancer still persists among many surgeons. The aim of the study was to determine
      whether TG in patients with distal stomach cancer offers a benefit in long term
      survival compared with DG. METHODS. Data on 180 consecutive patients with
      adenocarcinoma of the distal stomach that underwent surgery during the period
      2000-2003 were analyzed. Distal gastrectomy was performed on 91 patients (50.5%),
      and 89 patients (49.5%) underwent TG. RESULTS. The postoperative morbidity
      (anastomotic leakage, intraperitoneal hemorrhage and pulmonary complications) was
      significantly higher in the TG group than in the DG group. The TG group had a
      significantly higher rate of 30-day postoperative mortality than DG group, and a
      longer mean postoperative hospital stay. The 5-year survival rate was
      significantly higher for the DG group than for the TG group. The number of lymph
      node metastases and TNM stages are significant predictors of poor survival.
      CONCLUSIONS. Compared with patients undergoing TG, a better long-term survival
      time, lower postoperative morbidity and mortality rates and a lower
      hospitalization stay was obtained in patients that underwent DG for distal
      gastric cancer. This observation justifies the use of this procedure for the
      surgical therapy of the cancer of distal stomach.

PMID- 23539392
TI  - Pain palliation by endoscopic ultrasound-guided celiac plexus neurolysis in
      patients with unresectable pancreatic cancer.
AB  - BACKGROUND: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN)
      represents an alternative approach to pain palliation in patients with advanced
      pancreatic cancer. AIM: to evaluate the safety and initial efficacy of EUS-CPN in
      patients with painful unresectable pancreatic cancer. METHODS: Patients with
      inoperable body-tail pancreatic adenocarcinoma without prior chemotherapy and
      pain requiring opioid analgesia were included prospectively in this cohort study
      in a tertiary medical center. Central EUS-CPN was performed and the brief pain
      inventory and the Functional Assessment of Cancer Therapy measurement were
      applied before and 2 weeks after the procedure. RESULTS: Thirty-two patients
      underwent the procedure in one session without complications. Follow-up revealed
      overall pain relief in 24 patients (75%) and significant improvement in pain
      scores. Ratings of pain interfering with general activity, walking, work, mood,
      enjoyment of life, relations with others, and sleep improved significantly.
      Physical, functional, and emotional well-being improved significantly, except for
      acceptance of illness and enjoyment of life. CONCLUSION: Central EUS-CPN was an
      efficient and safe method for palliative pain management in our patients with
      inoperable pancreatic body-tail adenocarcinoma. The pain alleviation improved the
      patients' functional status, sleep, and quality of life, although other variables
      could also be involved, but acceptance of the illness and enjoyment of life did
      not change after treatment.

PMID- 23539393
TI  - Low bioavailability and traditional systemic steroids in IBD: can the former take
      over the latter?
AB  - Systemic corticosteroids have been used to treat active inflammatory bowel
      disease for over 50 years by virtue of their unquestionable efficacy in inducing
      clinical remission rapidly in the vast majority of patients. Nevertheless,
      traditional corticosteroids are associated to a plethora of potentially serious
      side effects due to their systemic metabolism; for this reason, interest has
      lately been growing in newer steroid compounds characterized by a high topical
      anti-inflammatory activity and a low systemic bioavailability. These compounds,
      namely budesonide and beclomethasone dipropionate--regarding the treatment of
      inflammatory bowel disease--can be administered orally and thanks to
      sophisticated delivery systems are conveyed specifically to the inflamed gut
      mucosa where they exert their anti-inflammatory action. After intestinal
      absorption, these drugs are promptly and efficiently inactivated by the liver, so
      that only inactive molecules reach the systemic circulation. This review revises
      the main clinical trials, meta-analyses and observational studies conducted on
      traditional and newer steroids, and critically interprets the main results
      achieved by these studies.

PMID- 23539394
TI  - Are there any alternative methods to hepatic venous pressure gradient in portal
      hypertension assessment?
AB  - Portal hypertension is a major consequence of any chronic liver disease and it
      represents the main mechanism of complication occurrence. Therefore, the
      assessment of portal hypertension presence is one of the most important steps in
      the management of any chronic liver diseases. The most accurate tool for portal
      pressure assessment is hepatic venous pressure gradient (HVPG) measurement, which
      has diagnostic and prognostic relevance. In this paper we review the methodology
      of HVPG measuring, together with the clinical relevance of this technique. Portal
      hypertension is defined as a HVPG higher than 5 mmHg, but clinically significant
      portal hypertension that predisposes to clinical decompensation is defined as
      HVPG higher than 10 mmHg. HVPG is useful for portal hypertension treatment
      monitoring. A decrease in HVPG greater than 20% or under the threshold of 12 mmHg
      is considered to be protective against portal hypertension-related events. Even
      if HVPG measurement is a safe procedure, it is still considered an invasive
      technique and not widely available. Therefore, non-invasive markers of portal
      hypertension were searched for. Until now only liver stiffness measurement by
      transient elastography has proved to be sufficiently accurate but there is still
      heterogeneity among the cut-off values for portal hypertension diagnosis.

PMID- 23539395
TI  - Dental treatment as a risk factor for hepatitis B and C viral infection. A review
      of the recent literature.
AB  - BACKGROUND & AIM: Patients chronically infected either with hepatitis B (HBV) or
      hepatitis C virus (HCV) are at increased risk of developing cirrhosis, end stage
      liver disease and hepatocellular carcinoma. Different risk factors were found to
      be associated with the transmission of these viruses in various settings. HBV and
      HCV transmission seems to be also acquired by non-parenteral and non-sexual
      routes. A large number of patients infected with HCV might have non identifiable
      routes of viral acquisition. Hence, viral hepatitis transmission risk factors
      identification is the main way to reduce infection. Dental treatment may be one
      of such risk factors, and this aspect is addressed in the present literature
      review, drawing information from existing literature. METHODS: An online database
      search was conducted, limited to publications from January 1999 to February 2012
      on specific aspects of HBV and HCV infection, including articles on risk factors,
      markers of infection, dentistry, epidemiology and transmission. Relevant material
      was evaluated and reviewed. RESULTS: Overall, 53 studies which met the selection
      criteria were evaluated. Although these studies were from different geographical
      regions of varied socioeconomic status and study populations and assessed
      different dental procedures, using different types of statistical analysis, we
      found that, although weak, there is an all-time risk of HBV and HCV infection
      during dental treatment. This is more important in developing countries where the
      rate of hepatitis infected individuals is higher. There is a need for more
      studies on this subject, properly planned, controlled and analyzed. CONCLUSION:
      Dental treatment can be included among the risk factors of HBV and HCV infection.
      This risk can easily be eliminated using standard precautionary measures.

PMID- 23539396
TI  - A case of fatal idiopathic enteritis and multiple opportunistic infections
      associated with dendritic cell deficiencies.
AB  - We present a case of an adult patient with new-onset severe, idiopathic, protein
      wasting enteropathy, in whom an extensive immunological workup was performed. We
      found a lack of dendritic cell (DC) subsets in the blood and bowel, as well as
      elevated circulating TGF-beta levels and decreased numbers of circulating FOXP3+
      regulatory T cells with diminished CTLA4 expression. She failed to respond to
      glucocorticoids and infliximab, and instead developed a constellation of
      opportunistic infections, including CMV ileitis, Mucormycosis, and Pneumocystis
      carinii pneumonia, and ultimately passed away. While the cause of her lack of DCs
      is unknown, this data suggests a key role for these cells in both regulating
      mucosal immunity and promoting effective cell-mediated immunity against pathogens
      in humans.

PMID- 23539397
TI  - Gastric carcinoids and therapeutic options. Case report and review of the
      literature.
AB  - Neuroendocrine tumors (carcinoids) are tumors originating from neuroendocrine
      cells. The distinction between different types of gastric carcinoids is important
      for their management. We present the case of a 38-year old woman with type 1
      gastric neuroendocrine tumors (NETs) associated with autoimmune atrophic
      gastritis. The management of these tumors has not been yet codified and different
      therapeutic strategies have been suggested. A proper evaluation before therapy is
      indicated in order to rule out both the malignant transformation as well as the
      presence of synchronous lesions, such as dysplasia or gastric adenocarcinoma. We
      describe our diagnostic and therapeutic strategies with references to previously
      published reports.

PMID- 23539398
TI  - Unknown complicated celiac disease as an unexpected finding in patients
      investigated with capsule endoscopy for Crohn's disease. A case series.
AB  - Atypical symptoms of celiac disease may cause a late diagnosis, revealed by the
      onset of complications, which may inaccurately be attributed to Crohn's disease,
      as manifestations frequently overlap. Assessing the entire small bowel mucosa,
      capsule endoscopy may be an accurate procedure in these challenging situations.
      We present four Crohn's disease patients diagnosed with ulcerative jejunoilieitis
      complicating celiac disease after capsule endoscopy procedure. In three of these
      patients, the ulcerative jejunoileitis led in time to stricture formation,
      suggesting Crohn's disease. Administration of non-steroidal anti-inflammatory
      drugs made the diagnosis even more difficult in one case. In patients with
      Crohn's disease not responding to immunosuppressive or biological treatment,
      complicated celiac disease should be considered and capsule endoscopy should be
      performed for reassessing the diagnosis.

PMID- 23539399
TI  - Type 1 diabetes mellitus with dual autoimmune mechanism related to pegylated
      interferon and ribavirin treatment for chronic HCV hepatitis.
AB  - We report a case of type 1 diabetes mellitus during pegylated interferon and
      ribavirin treatment for chronic hepatitis C, in a young man previously diagnosed
      with Hashimoto's thyroiditis and vitiligo. The diabetes mellitus occurred during
      the 12th month of therapy and the cessation of interferon was necessary. Besides
      anti-islet autoantibodies our patient had also anti-insulin receptor
      autoantibodies, which explains the type B insulin resistance. One year after
      interferon discontinuation the patient continues insulin treatment and all the
      pancreatic autoantibodies are still positive. Patients with autoimmune disorders
      should be closely monitored and periodically tested for pancreatic autoantibodies
      during interferon treatment, even in the absence of hyperglycemia.

PMID- 23539400
TI  - Radiofrequency ablation of splenic tumors: a case series.
AB  - Radiofrequency ablation (RFA) for treatment of splenic tumors has rarely been
      reported. Here we describe our experiences of undergoing RFA in three patients
      with solitary metastatic (n=2) and benign (n=1) tumors of the spleen. Two
      patients also had underlying cirrhotic hypersplenism. A 53-year-old male with
      solitary splenic metastasis from hepatocellular carcinoma underwent
      laparoscopical RFA of the splenic tumor. Another 61-year-old female with
      intraabdominal recurrence, focal splenic metastasis from colon cancer and
      cirrhotic hypersplenism underwent cytoreductive surgery and RFA of splenic
      tumors. On the third patient, a 32-year-old man with severe hypersplenism,
      splenic artery steal syndrome and a solitary splenic hemangioma, a laparoscopical
      RFA of the splenic tumor was performed. The three patients recovered
      uneventfully. The concurrent hypersplenism of the latter two patients improved
      significantly. The results indicate that RFA of splenic tumors is feasible and
      safe, and could be evaluated as an alternative to splenectomy in selected
      patients with solitary splenic tumors.

PMID- 23539401
TI  - Virtual colonoscopy is unlikely to reduce the need for optical colonoscopy.

PMID- 23539402
TI  - Reply: To PMID 23256122.

PMID- 23539403
TI  - Idiopathic hepatitis B surface antibody seroreversion after pegylated interferon
      alpha-2a therapy.

PMID- 23539404
TI  - Massive gastrointestinal bleeding during the course of chronic myelomonocytic
      leukemia.

PMID- 23539405
TI  - Giant esophageal lipoma presenting with gastroesophageal reflux symptoms.

PMID- 23539406
TI  - A case of lansoprazole-associated collagenous colitis with longitudinal ulcer.

PMID- 23539407
TI  - Chronic haematochezia caused by diffuse cavernous haemangioma of the rectum.

PMID- 23539408
TI  - To scope or to test for colorectal cancer screening?

PMID- 23539409
TI  - Gastric bezoars--diagnostic and therapeutic challenges.

PMID- 23539410
TI  - Outcome of hemodialysis patients with occult hepatitis B virus infection at a 4
      year follow-up.

PMID- 23539411
TI  - Is epistaxis associated with arterial hypertension? A systematic review of the
      literature.
AB  - Both epistaxis and hypertension are frequent problems in the adult population.
      The relationship between the level of arterial pressure and incidence of
      epistaxis in a patient with hypertension is a question that appears frequently in
      the clinical practice. A systematic review of the literature regarding the
      relation of arterial hypertension with epistaxis was performed through MEDLINE
      and EMBASE. All studies, whether examining the correlation of arterial pressure
      at presentation of a patient with nasal bleeding or the repercussion of episodes
      of epistaxis in hypertensive patients, were included in this review. Studies were
      evaluated independently by two reviewers according to a standard evaluation form.
      Overall, nine studies fulfilled our inclusion criteria. Five of them were single
      group (patient) studies, while the remaining four included a control group. In
      eight studies, the patient group included patients with epistaxis, while one
      focused on hypertensive patients. Six out of nine studies agree that arterial
      pressure is higher at the time of epistaxis, as compared to the control group or
      to the general population. Seven out of nine studies conclude that there is cross
      correlation between arterial pressure and the actual incident of epistaxis. The
      presence of high arterial blood pressure during the actual episode of nasal
      bleeding cannot establish a causative relationship with epistaxis, because of
      confounding stress and possible white coat phenomenon, but may lead to initial
      diagnosis of an already installed arterial hypertension. 

PMID- 23539412
TI  - Value of the video head impulse test in assessing vestibular deficits following
      vestibular neuritis.
AB  - To evaluate the performance of the video head impulse test (VHIT) in assessing
      vestibular deficit in vestibular neuritis. Test validation study was conducted in
      Tertiary referral center. Twenty-nine patients, referred for vestibular neuritis
      between October 2009 and March 2012, were included. We recorded age, gender,
      values of caloric deficit (caloric testing), and deficits in semicircular
      function (VHIT) at initial presentation and at the follow-up visit (1-3 months).
      Multivariate linear regression analysis was performed to determine variables
      associated with values of caloric testing at the follow-up visit. Diagnostic
      values of VHIT were compared with caloric testing data using the receiver
      operating characteristic (ROC) curve and subsequent statistical analysis. At the
      follow-up visit, complete recovery occurred in 31% of cases according to caloric
      evaluation, and VHIT normalized in 51.8%. Multivariate regression showed that a
      higher caloric deficit at the follow-up visit was associated with elevated age (p
      = 0.012) and high caloric deficit at initial presentation (p = 0.042). A lower
      caloric deficit was associated with normal VHIT results at the follow-up visit (p
      < 0.001). The ROC curve showed that specificity and sensitivity of VHIT were 100%
      when the caloric deficit was respectively lower than 40% or higher than 62.5%. At
      the caloric testing value of 30%, specificity was 100%, sensitivity 68.84%,
      positive predictive value 100% and negative predictive value 62.5%. VHIT is a
      fast, convenient and specific test to detect vestibular deficits in vestibular
      neuritis. However, VHIT lacks sensitivity by comparison with caloric testing,
      especially for moderate vestibular lesions.

PMID- 23539413
TI  - A ten-year experience of thyroglossal duct cyst surgery in children.
AB  - We discuss a 10-year experience of all the thyroglossal duct cysts (TGDC) removed
      at our institution, assessing whether management was appropriate and to compare
      our outcomes and success rate with current literature. We performed a
      retrospective review of TGDC surgery at our institution from 2000 to 2010. During
      the study period, 93 children were identified as having had a TGDC excision at an
      average age of 6.1 (1.1-15.3) years. Seventeen cases (18 %) were found to have
      not had their hyoid bone removed and of these 10 (59 %) were proven on histology
      to be non-TGDC. A total of 19 cases were confirmed TGDC on histology but received
      a non-Sistrunk's procedure and 12 (63 %) of those recurred requiring a more
      definitive procedure (i.e. Sistrunks). Of the 76 (82 %) that did have their hyoid
      bone removed 13 (17 %) suffered complications of which 3 were recurrences (3.9
      %), which is comparable to the literature (3-5 %). Of the complications that
      occurred 11 out of 13 (85 %) were infected cases at or around the time of
      procedure. Our experience, being the largest described in the United Kingdom
      supports the use of Sistrunk's procedure with recurrence rates comparable to that
      within the literature. 

PMID- 23539415
TI  - Thrombolytic therapy for acute pulmonary embolism.
AB  - Thrombolytic therapy accelerates the dissolution of acute pulmonary embolism and
      is potentially lifesaving. The goal of this article is to offer a critical
      analysis of the use of thrombolytic therapy in this setting. Guidelines have been
      written and modified and new ones have been published over the past several
      years. Although an evidence base exists, unanswered questions remain. Despite the
      potential benefit of rapid clot lysis, nonpathologic thrombi are also lysed, so
      that thrombolytic therapy can cause significant bleeding complications. Massive
      acute pulmonary embolism is the clearest indication for these drugs, and although
      thrombolysis has been studied in submassive pulmonary embolism, this scenario
      remains more controversial. Traditionally, thrombolytic agents have been
      delivered intravenously, but intraembolic therapy via a pulmonary artery catheter
      has gained momentum. Few randomized trials have been conducted, however. Only
      three agents have been approved for use in the United States: streptokinase,
      urokinase, and tissue-type plasminogen activator. Urokinase is not currently
      available for use in the United States. The latter agent has been most widely
      used on the basis of proven benefit with a relatively short (2-hour) infusion.
      Newer, unapproved agents include tenecteplase and reteplase. Risk stratification
      in acute pulmonary embolism is important in determining which patients are the
      most appropriate candidates for thrombolysis, with careful consideration of
      contraindications.

PMID- 23539417
TI  - New Local Estimation Procedure for Nonparametric Regression Function of
      Longitudinal Data.
AB  - This paper develops a new estimation of nonparametric regression functions for
      clustered or longitudinal data. We propose to use Cholesky decomposition and
      profile least squares techniques to estimate the correlation structure and
      regression function simultaneously. We further prove that the proposed estimator
      is as asymptotically efficient as if the covariance matrix were known. A Monte
      Carlo simulation study is conducted to examine the finite sample performance of
      the proposed procedure, and to compare the proposed procedure with the existing
      ones. Based on our empirical studies, the newly proposed procedure works better
      than the naive local linear regression with working independence error structure
      and the efficiency gain can be achieved in moderate-sized samples. Our numerical
      comparison also shows that the newly proposed procedure outperforms some existing
      ones. A real data set application is also provided to illustrate the proposed
      estimation procedure.

PMID- 23539418
TI  - Investigation of Acid-Etched CO2 Laser Ablated Enamel Surfaces Using Polarization
      Sensitive Optical Coherence Tomography.
AB  - A carbon dioxide laser operating at the highly absorbed wavelength of 9.3MUm with
      a pulse duration of 10-15MUs is ideally suited for caries removal and caries
      prevention. The enamel thermally modified by the laser has enhanced resistance to
      acid dissolution. This is an obvious advantage for caries prevention; however, it
      is often necessary to etch the enamel surface to increase adhesion to composite
      restorative materials and such surfaces may be more resistant to etching. The
      purpose of the study was to non-destructively measure the susceptibility of laser
      ablated enamel surfaces to acid dissolution before and after acid-etching using
      Polarization Sensitive Optical Coherence Tomography (PS-OCT). PS-OCT was used to
      acquire images of bovine enamel surfaces after exposure to laser irradiation at
      ablative fluence, acid-etching, and a surface softened dissolution model. The
      integrated reflectivity from lesion and the lesion depth were measured using PS
      OCT. Samples were also sectioned for examination by Polarized Light Microscopy
      (PLM). PS-OCT images showed that acid-etching greatly accelerated the formation
      of subsurface lesions on both laser-irradiated and non-irradiated surfaces
      (P<0.05). A 37.5% phosphoric acid etch removed the laser modified enamel layer
      after 5-10 seconds.

PMID- 23539414
TI  - Plasminogen activators and ischemic stroke: conditions for acute delivery.
AB  - Appropriate acute treatment with plasminogen activators (PAs) can significantly
      increase the probability of minimal or no disability in selected ischemic stroke
      patients. There is a great deal of evidence showing that intravenous recombinant
      tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs
      has also been demonstrated in the development of this treatment. Recanalization
      of symptomatic, documented carotid or vertebrobasilar arterial territory
      occlusions have also been achieved by local intra-arterial PA delivery, although
      only a single prospective double-blinded randomized placebo-controlled study has
      been reported. The increase in intracerebral hemorrhage with these agents by
      either delivery approach underscores the need for careful patient selection, dose
      appropriate safety and efficacy, proper clinical trial design, and an
      understanding of the evolution of cerebral tissue injury due to focal ischemia.
      Principles underlying the evolution of focal ischemia have been expanded by
      experience with acute PA intervention. Several questions remain open that concern
      the manner in which PAs can be applied acutely in ischemic stroke and how injury
      development can be limited.

PMID- 23539416
TI  - Esophageal cancer alters the expression of nuclear pore complex binding protein
      Hsc70 and eIF5A-1.
AB  - Nuclear pore complex (NPC) is the only corridor for macromolecules exchange
      between nucleus and cytoplasm. NPC and its components, nucleoporins, play
      important role in the diverse physiological processes including macromolecule
      exchange, chromosome segregation, apoptosis and gene expression. Recent reports
      also suggest involvement of nucleoporins in carcinogenesis. Applying proteomics,
      we analyzed expression pattern of the NPC components in a newly established
      esophageal cancer cell line from Persia (Iran), the high-risk region for
      esophageal cancer. Our results indicate overexpression of Hsc70 and
      downregulation of subunit alpha type-3 of proteasome, calpain small subunit 1,
      and eIF5A-1. Among these proteins, Hsc70 and eIF5A-1 are in direct interaction
      with NPC and involved in the nucleocytoplasmic exchange. Hsc70 plays a critical
      role as a chaperone in the formation of a cargo-receptor complex in
      nucleocytoplasmic transport. On the other hand, it is an NPC-associated protein
      that binds to nucleoporins and contributes in recycling of the nucleocytoplasmic
      transport receptors in mammals and affects transport of proteins between nucleus
      and cytoplasm. The other nuclear pore interacting protein: eIF5A-1 binds to the
      several nucleoporins and participates in nucleocytoplasmic transport. Altered
      expression of Hsc70 and eIF5A-1 may cause defects in nucleocytoplasmic transport
      and play a role in esophageal carcinogenesis.

PMID- 23539419
TI  - Modified Blalock Taussig shunt: a not-so-simple palliative procedure.
AB  - OBJECTIVES: Thirty-two consecutive isolated modified Blalock Taussig (BT) shunts
      performed in infancy since 2004 were reviewed and analysed to identify the risk
      factors for shunt intervention and mortality. METHODS: Sternotomy was the only
      approach used. Median age and weight were 10.5 (range 1-74) days and 2.9 (1.9
      4.4) kg, respectively. Shunt palliation was performed for biventricular hearts
      (Tetralogy of Fallot/double outlet right ventricle/transposition of great
      arteries_ventricular septal defect_pulmonary stenosis/pulmonary
      atresia_ventricular septal defect/others) in 21, and univentricular hearts in 11,
      patients. Hypoplastic left heart syndrome patients were excluded. Two procedures
      required cardiopulmonary bypass. Median shunt size was 3.5 (3-4) mm and median
      shunt size/kg body weight was 1.2 (0.9-1.7) mm/kg. Reduction in shunt size was
      necessary in 5 of 32 (16%) patients. RESULTS: Three of 32 (9%) patients died
      after 3 (1-15) days due to cardiorespiratory decompensation. Lower body weight (P
      = 0.04) and bigger shunt size/kg of body weight (P = 0.004) were significant risk
      factors for mortality. Acute shunt thrombosis was observed in 3 of 32 (9%), none
      leading to death. Need for cardiac decongestive therapy was associated with
      univentricular hearts (P < 0.001), bigger shunt size (P = 0.054) and longer
      hospital stay (P = 0.005). Twenty-eight patients have undergone a successful
      shunt takedown at a median age of 5.5 (0.5-11.9) months, without late mortality.
      CONCLUSIONS: Palliation with a modified BT shunt continues to be indicated
      despite increased thrust on primary corrective surgery. Though seemingly simple,
      it is associated with significant morbidity and mortality. Effective over
      shunting and acute shunt thrombosis are the lingering problems of shunt therapy.

PMID- 23539420
TI  - Total aortic arch replacement in 2013: where do we go from here?

PMID- 23539421
TI  - The challenge of home discharge with a total artificial heart: the La Pitie
      Salpetriere experience.
AB  - OBJECTIVES: The total artificial heart (TAH) helps to counteract the current
      decrease in heart donors and is likely to bridge patients to transplant under
      favourable conditions. Today's mobile consoles facilitate home discharge. The aim
      of this study was to report on the La Pitie Hospital experience with CardioWest
      TAH recipients, and more particularly, on generally successful outpatient'
      management. METHODS: A retrospective analysis was performed on clinical and
      biological data from patients implanted with a TAH between December 2006 and July
      2010 in a single institution. Morbi-mortality during hospital stay, number and
      causes of rehospitalizations, quality of life during home discharge, bridge to
      transplant results and survival have all been analysed. RESULTS: Twenty-seven
      patients were implanted with the CardioWest. Fifteen patients (55.5%) died during
      support. Prior to home discharge, the most frequent cause of death was multi
      organ failure (46.6%). Twelve patients were discharged home from hospital within
      a median of 88 days [range 35-152, interquartile range 57] postimplantation. Mean
      rehospitalization rate was 1.2 by patient, on account of device infection (n =
      7), technical problems with the console (n = 3) and other causes (n = 4). Between
      discharge and transplant, patients spent 87% of their support time out of
      hospital. All patients who returned home with the TAH were subsequently
      transplanted, and 1 died in post-transplant. CONCLUSION: Despite the morbidity
      and mortality occurring during the postimplantation period, home discharge with a
      TAH is possible. Portables drivers allow for a safe return home. Aside from some
      remaining weak points such as infectious complications or noise, CardioWest TAH
      allows for successful rehabilitation of graft candidates, and assures highly
      satisfactory transplant results.

PMID- 23539422
TI  - Continuously Tunable 250 GHz Gyrotron with a Double Disk Window for DNP-NMR
      Spectroscopy.
AB  - In this paper, we describe the design and experimental results from the rebuild
      of a 250 GHz gyrotron used for Dynamic Nuclear Polarization enhanced Nuclear
      Magnetic Resonance spectroscopy on a 380 MHz spectrometer. Tuning bandwidth of
      approximately 2 GHz is easily achieved at a fixed magnetic field of 9.24 T and a
      beam current of 95 mA producing an average output power of >10 W over the entire
      tuning band. This tube incorporates a double disk output sapphire window in order
      to maximize the transmission at 250.58 GHz. DNP Signal enhancement of >125 is
      achieved on a 13C-Urea sample using this gyrotron.

PMID- 23539423
TI  - Pharmacokinetics of angiotensin II receptor blockers in the dog following a
      single oral administration.
AB  - Angiotensin II receptor blockers (ARBs) are effective and well-tolerated orally
      active anti-hypertensive agents. The purpose of this study was to investigate the
      pharmacokinetic properties of typical ARBs in the dog. 60 beagles were
      administered a single oral dose of Micardis(r) 80 mg (telmisartan), Cozaar(r) 50
      mg (losartan), or Diovan(r) 80- and 160-mg (valsartan). The plasma concentrations
      of these ARBs were measured using liquid chromatography/tandem mass spectrometry
      and their pharmacokinetic properties were analyzed using both non-compartmental
      and compartmental approaches. The half-life and volume of distribution in dogs
      were in the order losartan>valsartan>telmisartan after oral administration.
      Systemic exposure was estimated by calculating the area under the plasma
      concentration-vs.-time curve from time zero to infinity (AUC inf ), and resulted
      in the order telmisartan>valsartan>losartan. The values of C max and AUC
      increased in proportion to the dose of valsartan. In compartmental analysis, the
      pharmacokinetics of telmisartan and losartan pharmacokinetics fit a 2-compartment
      model, while valsartan fit a 1-compartment model. These results provide detailed
      pharmacokinetic information of ARBs in the dog, and may aid in future development
      of improved formulations or fixed-dose combinations. 

PMID- 23539424
TI  - Synthesis and anticonvulsant activity evaluation of 4-(2-alkoxy-phenyl)-2,4
      dihydro-3H-1,2,4-triazol-3-ones in various experimental seizure models in mice.
AB  - A new series of 4-(2-alkoxy-phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones was
      synthesized using appropriate synthetic route. Their anticonvulsant activities
      were evaluated experimentally against maximal electroshock test and their
      neurotoxicities were evaluated under the rotarod neurotoxicity test with
      intraperitoneally injected mice. The results showed that all target compounds
      exhibited anticonvulsant activity in varying degrees against maximal electroshock
      test. Among them, 4-(2-octyloxy-phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (5 g)
      was the most promising compound with the median effective dose (ED50) of 23.7
      mg/kg, the median toxicity dose (TD50) of 611.0 mg/kg, and the protective index
      (PI) of 25.8. Compound 5 g showed the higher safety than the standard
      carbamazepine (PI=6.5). As well as demonstrating the anti-MES efficacy of
      compound 5 g, its potency against seizures induced by pentylenetetrazole, 3
      mercaptopropionic acid, and bicuculline were also established, with the results
      suggesting that GABA-mediated mechanisms might be involved in its anticonvulsant
      activity. 

PMID- 23539425
TI  - Effects of andrographolide on the pharmacokinetics of aminophylline and
      doxofylline in rats.
AB  - Andrographolide, which is one of the main pharmaceutical ingredients in
      traditional Chinese medicine Andrographis paniculata, can clear heat, detoxify
      human body, cool blood and reduce swelling, etc. Respiratory tract infectious
      diseases have been treated with the combination of andrographolide and
      theophyllines clinically. As andrographolide inhibits the CYP1A2 activity in
      vitro, it potentially interacts with theophyllines that are mainly metabolized by
      CYP1A2. Therefore, we herein studied the effects of andrographolide on the
      pharmacokinetics of aminophylline and doxofylline in rats. The blood drug
      concentrations of aminophylline, doxofylline and its metabolite theophylline were
      determined by HPLC. The theophylline AUC(0-t) was significantly elevated
      confronting the combination of andrographolide and aminophylline compared to that
      of the control group (P<0.05). Meanwhile, when only aminophylline was used, the
      theophylline clearance rate was significantly higher than those in the case of
      combination (P<0.05). The pharmacokinetics parameters of doxofylline and its
      metabolite theophylline in the individual administration group showed no
      significantly different from that combined with andrographolide. The results
      suggest that andrographolide and aminophylline should not be simultaneously
      administered because the former may raise the risks of side effects by inhibiting
      the clearance of the latter. In contrast, it is more secure to combine
      doxofylline with andrographolide owing to the almost intact pharmacokinetics.

PMID- 23539426
TI  - Potent and prolonged hypoglycemic activity of an oral insulin--Tat mixture in
      diabetic mice.
AB  - Trans-activator of transcription (Tat) is a cell penetrating peptide which can
      translocate and carry macromolecular cargoes through cell membranes. This study
      investigated the hypoglycemic activity of orally delivered insulin - Tat mixture
      in alloxan-induced diabetic mice. The mixtures of insulin and Tat at 1:1, 1:3 and
      1:6 molar ratios were given orally at the insulin doses ranging from 1-200 IU/kg.
      The fasting blood glucose (FBG) levels were measured at initial, 1, 2, 4, 6, and
      12 h after administration. At 1:3 molar ratio of the mixture and after 12 h of
      administration, insulin at 200 IU/kg showed the highest with prolonged
      hypoglycemic activity of 74.0+/-10.3% FBG reduction (2.18 folds of subcutaneously
      injected (SC) insulin). Free insulin administered orally did not show any
      hypoglycemic activity. The mixtures at the insulin doses of 100 and 50 IU/kg also
      showed potent FBG reduction of 73.8+/-8.2 and 71.3+/-16.9% at 12 h after
      administration (2.18 and 2.10 folds of SC insulin, respectively). After
      incubation with Mono-Mac-6 cells, only the -mixtures but not the free insulin
      showed intra-cellular insulin uptake, indicating the insulin penetration through
      the cell membranes via Tat. In simulated gastric fluid, the insulin content in
      the mixture was not found, demonstrating the degradation of insulin in the
      gastric environments. Insulin may be absorbed at upper gastrointestinal tract
      facilitated by Tat. The potent and prolonged hypoglycemic activity of insulin co
      administered orally with Tat can be further developed as an effective oral
      insulin delivery system. 

PMID- 23539427
TI  - Bioequivalence study of 2 formulations of film-coated tablets containing a fixed
      dose combination of bisoprolol fumarate 5 mg and hydrochlorothiazide 6.25 mg in
      healthy subjects.
AB  - BACKGROUND: The present study was conducted to compare the bioavailability of 2
      formulations of fixed-dose combination of bisoprolol fumarate 5 mg and
      hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (test and reference
      formulations). METHODS: This study was a randomized, single-blind, 2-period, 2
      sequence cross-over study which included 18 healthy adult male and female
      subjects under fasting condition. The pharmacokinetic parameters, AUCt, AUCinf,
      Cmax, tmax, and t1/2 were determined based on the concentrations of bisoprolol
      (CAS 66722-44-9) and HCT (CAS 58-93-5), using ultra-performance liquid
      chromatography with tandem mass spectrometer detector (UPLC-MS/MS). In each of
      the 2 study periods (with a washout of 1 week) a single dose of test or reference
      product was administered. RESULTS: The geometric mean ratios (90% CI) of the test
      drug/reference drug for bisoprolol were 97.22% (93.75-100.83%) for AUCt(0-48),
      97.20% (93.97-100.54%) for AUCinf, and 100.36% (93.83-107.34%) for Cmax; while
      those for HCT were 93.22% (84.72-102.57%), 93.39% (85.43-102.10%) and 99.39%
      (85.45-115.61%), for AUCt(0-24), AUCinf, and Cmax, respectively. The differences
      between the test and reference drug products for tmax values of bisoprolol as
      well as t1/2 values of both bisoprolol and hydrochlorothiazide were not
      statistically significant; yet, the difference was statistically significant for
      the tmax values of hydrochlorothiazide. There was no adverse event encountered
      during this bioequivalence test. MAJOR CONCLUSION: It was concluded that the 2
      formulations of fixed dose combination of bisoprolol fumarate 5 mg and
      hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (the test and reference
      products) were bioequivalent.

PMID- 23539428
TI  - Pharmacokinetics of a new tetramethylpyrazine analogue CXC195 in rats.
AB  - To investigate the pharmacokinetical characteristics of a new neuroprotective
      drug CXC195 after intraperitoneal injection in rats.A single 10 mg . kg-1 of
      CXC195 was intraperitoneally injected to 8 rats after fasting overnight,
      respectively. 500 microliters of blood samples were collected at scheduled time
      before and after administration. CXC195 in rats' plasma was separated on a
      Diamonsil C18 column (150 mm*4.6 mm, 5 MUm), eluted using methanol - 0.05 mM
      NaH2PO4 solution (86:14, v/v) as mobile phase, and detected by UV detector at
      wavelength of 278 nm. The plasma concentration of CXC195 was determined by
      established HPLC method after disposition and its pharmacokinetic parameters were
      analyzed and evaluated by Drug and Statistic (version 2.0).The Cmax, Tmax, t1/2,
      AUC0-8, AUC0-infinity, MRT0-8, MRT0-infinity, CL/F and V/F of CXC195 after-single
      dose intraperitoneal injection of 10 mg . kg-1 CXC195 were 12.37+/-5.35 MUg . mL
      1, 0.5+/-0.21 h,4.24+/-2.43 h, 24.89+/-8.32 MUg . mL-1 . h, 28.57+/-9.66 MUg . mL
      1 . h, 2.00+/-0.53 h, 2.93+/-0.75 h, 1.4+/-0.73 L . h-1 and 1.16+/-0.68 L.The
      established HPLC method was sensitive, rapid, and suitable for CXC195
      pharmacokinetic study. The procedure of CXC195 in rat was fit to double
      compartmental model with lag time of 0.13 h. 

PMID- 23539429
TI  - Investigation of the pharmacokinetic interaction between ritonavir and CMDCK, a
      new non-nucleoside reverse transcriptase inhibitor.
AB  - The aim of this study was to investigate the pharmacokinetic interaction between
      ritonavir (RTV) and an anti-HIV agent 3-cyanomethyl-4-methyl-DCK (CMDCK). CMDCK
      was administered orally (8 mg/kg) and intravenously (2 mg/kg) to rats in the
      absence or presence of RTV (1 or 2.5 mg/kg). By comparing the pharmacokinetic
      parameters between the control and the RTV treated groups, it was found that co
      administration with RTV could significantly increase the plasma exposure of
      CMDCK, through improving the hepatic and intestinal availabilities. The AUCinf of
      CMDCK was increased by 2.4 or 8.7 times for intravenous or oral route,
      respectively. The oral bioavailability of CMDCK was increased from 15% of the
      control group to 45% of the RTV concomitant group (2.5 mg/kg). In the in vitro
      studies with liver and intestinal microsomes, the K i values of RTV on the CMDCK
      metabolism were determined and found to be 0.22 and 0.48 uM for human, 0.33 and
      1.60 uM for rat, respectively. Caco-2 cells study showed that CMDCK is not a P
      glycoprotein (P-gp) substrate and its transepithelial transport is mainly through
      passive diffusion. The in vitro and in vivo results indicate that RTV could
      improve the bioavailability of CMDCK by inhibiting CYP3A mediated metabolism in
      both liver and intestine.

PMID- 23539430
TI  - Long-term sequelae of childhood bacterial meningitis.
AB  - In most high-income countries, fewer children now acquire meningitis, and many of
      those who do will survive. Globally, however, meningitis still remains a
      significant cause of child morbidity and mortality. In this article, the authors
      review recent evidence on the morbidity faced by childhood survivors of bacterial
      meningitis. Outcomes vary by bacterial pathogen, with around a 20 % risk for
      severe sequelae (most commonly, neurocognitive) by all pathogenic causes.
      Pneumococcal, tuberculosis, and group B streptococcal meningitis lead to the
      highest rates of sequelae. Recent epidemiological shifts in the major pathogens
      causing meningitis, as well as varied regional settings between studies, limit
      generalizability of evidence in the literature, and better research using
      longitudinal data and case-control methodology is required, especially in low
      income countries. However, the consistently high levels of complications
      described in the literature call for more widespread vaccination programs for
      prevention and a greater focus on potential complications by educators and health
      care providers to support childhood survivors of bacterial meningitis and their
      families.

PMID- 23539432
TI  - Freedom of conscience and health care in the United States of america: the
      conflict between public health and religious liberty in the patient protection
      and affordable care act.
AB  - The recent confirmation of the constitutionality of the Obama administration's
      Patient Protection and Affordable Care Act (PPACA) by the US Supreme Court has
      brought to the fore long-standing debates over individual liberty and religious
      freedom. Advocates of personal liberty are often critical, particularly in the
      USA, of public health measures which they deem to be overly restrictive of
      personal choice. In addition to the alleged restrictions of individual freedom of
      choice when it comes to the question of whether or not to purchase health
      insurance, opponents to the PPACA also argue that certain requirements of the Act
      violate the right to freedom of conscience by mandating support for services
      deemed immoral by religious groups. These issues continue the long running debate
      surrounding the demands of religious groups for special consideration in the
      realm of health care provision. In this paper I examine the requirements of the
      PPACA, and the impacts that religious, and other ideological, exemptions can have
      on public health, and argue that the exemptions provided for by the PPACA do not
      in fact impose unreasonable restrictions on religious freedom, but rather concede
      too much and in so doing endanger public health and some important individual
      liberties. 

PMID- 23539431
TI  - Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: a systematic
      review.
AB  - AIM: To investigate potential therapeutic recommendations for endoscopic and
      surgical resection of T1a/T1b esophageal neoplasms. METHODS: A thorough search of
      electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up
      to January 2011 was performed. An analysis was carried out, pooling the effects
      of outcomes of 4241 patients enrolled in 80 retrospective studies. For
      comparisons across studies, each reporting on only one endoscopic method, we used
      a random effects meta-regression of the log-odds of the outcome of treatment in
      each study. "Neural networks" as a data mining technique was employed in order to
      establish a prediction model of lymph node status in superficial submucosal
      esophageal carcinoma. Another data mining technique, the "feature selection and
      root cause analysis", was used to identify the most important predictors of local
      recurrence and metachronous cancer development in endoscopically resected
      patients, and lymph node positivity in squamous carcinoma (SCC) and
      adenocarcinoma (ADC) separately in surgically resected patients. RESULTS:
      Endoscopically resected patients: Low grade dysplasia was observed in 4% of
      patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer
      in 54%, and submucosal cancer in 16% of patients. There were no significant
      differences between endoscopic mucosal resection and endoscopic submucosal
      dissection (ESD) for the following parameters: complications, patients submitted
      to surgery, positive margins, lymph node positivity, local recurrence and
      metachronous cancer. With regard to piecemeal resection, ESD performed better
      since the number of cases was significantly less [coefficient: -7.709438, 95%CI:
      (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were
      significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559), P <
      0.01]. A higher rate of esophageal stenosis was observed following ESD
      [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly
      greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206
      +/- 0.6249 vs SCC: 4.1356 +/- 0.4038, P < 0.05). The odds for re-classification
      of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC,
      respectively. Local tumor recurrence was best predicted by grade 3
      differentiation and piecemeal resection, metachronous cancer development by the
      carcinoma in situ component, and lymph node positivity by lymphovascular
      invasion. With regard to surgically resected patients: Significant differences in
      patients with positive lymph nodes were observed between ADC and SCC
      [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P < 0.01). In contrast,
      lymphovascular and microvascular invasion and grade 3 patients between histologic
      types were comparable, the respective rank order of the predictors of lymph node
      positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion
      (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type
      (ADC/SCC) was not included in the model. The best predictors for SCC lymph node
      positivity were Sm3 invasion and (V+). For ADC, the most important predictor was
      (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous
      cancer by the carcinoma in-situ component, and lymph node positivity by L+. T1b
      cancer should be treated with surgical resection.

PMID- 23539433
TI  - The onset of STI diagnosis through age 30: results from the Seattle Social
      Development Project Intervention.
AB  - The objectives of this study were to examine (1) whether the onset of sexually
      transmitted infections (STI) through age 30 differed for youths who received a
      social developmental intervention during elementary grades compared to those in
      the control condition; (2) potential social-developmental mediators of this
      intervention; and (3) the extent to which these results differed by ethnicity. A
      nonrandomized controlled trial followed participants to age 30, 18 years after
      the intervention ended. Three intervention conditions were compared: a full
      intervention group, assigned to intervention in grades 1 through 6; a late
      intervention group, assigned to intervention in grades 5 and 6 only; and a no
      treatment control group. Eighteen public elementary schools serving diverse
      neighborhoods including high-crime neighborhoods of Seattle are the setting of
      the study. Six hundred eight participants in three intervention conditions were
      interviewed from age 10 through 30. Interventions include teacher training in
      classroom instruction and management, child social and emotional skill
      development, and parent workshops. Outcome is the cumulative onset of participant
      report of STI diagnosis. Adolescent family environment, bonding to school,
      antisocial peer affiliation, early sex initiation, alcohol use, cigarette use,
      and marijuana use were tested as potential intervention mechanisms. Complementary
      log-log survival analysis found significantly lower odds of STI onset for the
      full-intervention compared to the control condition. The lowering of STI onset
      risk was significantly greater for African Americans and Asian Americans compared
      to European Americans. Family environment, school bonding, and delayed initiation
      of sexual behavior mediated the relationship between treatment and STI hazard. A
      universal intervention for urban elementary school children, focused on classroom
      management and instruction, children's social competence, and parenting practices
      may reduce the onset of STI through age 30, especially for African Americans.

PMID- 23539434
TI  - Case report and review of esophageal lichen planus treated with fluticasone.
AB  - Lichen planus is a fairly common chronic idiopathic disorder of the skin, nails
      and mucosal surfaces. Esophageal involvement of this disease on the other hand is
      rare and only about 50 cases have been reported in literature. Given its rarity,
      it can be difficult to diagnose and may be easily misdiagnosed as reflux
      esophagitis. Currently, there are no clear recommendations on the optimal
      management of this disease and little is known about the best treatment approach.
      Systemic steroids are usually the first line treatment and offer a favorable
      response. In this report, we would like to present a novel approach in the
      management of esophageal lichen planus in a middle-aged woman treated
      successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk,
      as evidenced by objective clinical findings. Based on our review of related
      literature and experience in this patient, we feel that a trial of swallowed
      fluticasone may be a prudent approach in the management of these patients since
      it has a more favorable side effect profile than systemic treatment.

PMID- 23539436
TI  - Circulating tumor cells in high-risk nonmetastatic colorectal cancer.
AB  - The identification of patients at higher risk of recurrence after primary
      colorectal cancer resection is currently one of the challenges facing medical
      oncologists. Circulating tumor cell (CTC) may represent a surrogate marker of an
      early spread of disease in patients without overt metastases. Thirty-seven high
      risk stages II-III colorectal cancer patients were evaluated for the presence of
      CTC. Enumeration of CTCs in 7.5 ml of blood was carried out with the FDA-cleared
      CellSearch system. CTC count was performed after primary tumor resection and
      before the start of adjuvant therapy. CTC was detected in 22 % of patients with a
      significant correlation with regional lymph nodes involvement and stage of
      disease. No significant correlation was found among the presence of CTC and other
      clinicopathological parameters. These data suggest that CTCs detection might help
      in the selection of high-risk stage II colorectal cancer patient candidates for
      adjuvant chemotherapy.

PMID- 23539435
TI  - MicroRNA-31-5p modulates cell cycle by targeting human mutL homolog 1 in human
      cancer cells.
AB  - MicroRNAs (miRNAs) and DNA mismatch repair (MMR) have been linked to human cancer
      progression. Human mutL homolog 1 (hMLH1), one of the core MMR genes, defects in
      lung cancer development. However, the interaction between miRNAs and MMR genes
      and their regulatory effect on cell cycle remain poorly understood. In this
      study, we investigated the role of miR-31-5p in hMLH1 gene expression and the
      effect of miR-31-5p on cell cycle in non-small cell lung cancer (NSCLC). We found
      that miR-31-5p was inversely correlated with hMLH1 expression in NSCLC cell lines
      and hMLH1 was a direct target of miR-31-5p. Knockdown of miR-31-5p induced a cell
      cycle arrest at G2/M phase and increased hMLH1 protein expression in NSCLC cells.
      Conversely, overexpression of miR-31-5p significantly induced cell cycle arrest
      at S phase and decreased hMLH1 protein expression. Furthermore, knockdown of
      hMLH1 upregulated miR-31-5p expression and caused cell cycle arrest at S phase.
      Data from this study revealed that miR-31-5p modulates cell cycle by targeting
      hMLH1 protein at the posttranscriptional level in NSCLC, which may represent a
      novel therapy strategy for lung cancer by targeting miR-31-5p.

PMID- 23539437
TI  - Phenotypic and Genotypic Characterization of Escherichia coli Isolated from
      Untreated Surface Waters.
AB  - A common member of the intestinal microbiota in humans and animals is Escherichia
      coli. Based on the presence of virulence factors, E. coli can be potentially
      pathogenic. The focus of this study was to isolate E. coli from untreated surface
      waters (37 sites) in Illinois and Missouri and determine phenotypic and genotypic
      diversity among isolates. Water samples positive for fecal coliforms based on the
      Colisure((r)) test were streaked directly onto Eosin Methylene Blue (EMB) agar
      (37 degrees C) or transferred to EC broth (44.5 degrees C). EC broth cultures
      producing gas were then streaked onto EMB agar. Forty-five isolates were
      identified as E. coli using API 20E and Enterotube II identification systems, and
      some phenotypic variation was observed in metabolism and fermentation. Antibiotic
      susceptibility of each isolate was also determined using the Kirby-Bauer Method.
      Differential responses to 10 antimicrobial agents were seen with 7, 16, 2, and 9
      of the isolates resistant to ampicillin, cephalothin, tetracycline, and triple
      sulfonamide, respectively. All of the isolates were susceptible or intermediate
      to amoxicillin, ciprofloxacin, polymyxin B, gentamicin, imipenem, and nalidixic
      acid. Genotypic variation was assessed through multiplex Polymerase Chain
      Reaction for four virulence genes (stx1 and stx2 [shiga toxin], eaeA [intimin];
      and hlyA [enterohemolysin]) and one housekeeping gene (uidA [beta-D
      glucuronidase]). Genotypic variation was observed with two of the isolates
      possessing the virulence gene (eaeA) for intimin. These findings increase our
      understanding of the diversity of E. coli in the environment which will
      ultimately help in the assessment of this organism and its role in public health.

PMID- 23539438
TI  - A psychological autopsy study of suicide among Inuit in Nunavut: methodological
      and ethical considerations, feasibility and acceptability.
AB  - INTRODUCTION: The increasing global prevalence of suicide has made it a major
      public health concern. Research designed to retrospectively study suicide cases
      is now being conducted in populations around the world. This field of research is
      especially crucial in Aboriginal populations, as they often have higher suicide
      rates than the rest of the country. OBJECTIVE: This article presents the
      methodological aspects of the first psychological autopsy study on suicide among
      Inuit in Nunavut. Qaujivallianiq Inuusirijauvalauqtunik (Learning from lives that
      have been lived) is a large case-control study, including all 120 cases of
      suicide by Inuit that occurred in Nunavut between 1 January 2003 and 31 December
      2006. The article describes the research design, ethical considerations and
      strategies used to adapt the psychological autopsy method to Nunavut Inuit.
      Specifically, we present local social and cultural issues; data collection
      procedures; and the acceptability, reliability and validity of the method.
      METHOD: A retrospective case-control study using the psychological autopsy
      approach was carried out in 22 communities in Nunavut. A total of 498 individuals
      were directly interviewed, and medical and correctional charts were also
      reviewed. RESULTS: The psychological autopsy method was well received by
      participants as they appreciated the opportunity to discuss the loss of a family
      member or friend by suicide. During interviews, informants readily identified
      symptoms of psychiatric disorders, although culture-specific rather than clinical
      explanations were sometimes provided. Results suggest that the psychological
      autopsy method can be effectively used in Inuit populations.

PMID- 23539440
TI  - A critique of RPE as a basis of exercise prescription.

PMID- 23539439
TI  - Space physiology IV: mathematical modeling of the cardiovascular system in space
      exploration.
AB  - Mathematical modeling represents an important tool for analyzing cardiovascular
      function during spaceflight. This review describes how modeling of the
      cardiovascular system can contribute to space life science research and
      illustrates this process via modeling efforts to study postflight orthostatic
      intolerance (POI), a key issue for spaceflight. Examining this application also
      provides a context for considering broader applications of modeling techniques to
      the challenges of bioastronautics. POI, which affects a large fraction of
      astronauts in stand tests upon return to Earth, presents as dizziness, fainting
      and other symptoms, which can diminish crew performance and cause safety hazards.
      POI on the Moon or Mars could be more critical. In the field of bioastronautics,
      POI has been the dominant application of cardiovascular modeling for more than a
      decade, and a number of mechanisms for POI have been investigated. Modeling
      approaches include computational models with a range of incorporated factors and
      hemodynamic sophistication, and also physical models tested in parabolic and
      orbital flight. Mathematical methods such as parameter sensitivity analysis can
      help identify key system mechanisms. In the case of POI, this could lead to more
      effective countermeasures. Validation is a persistent issue in modeling efforts,
      and key considerations and needs for experimental data to synergistically improve
      understanding of cardiovascular responses are outlined. Future directions in
      cardiovascular modeling include subject-specific assessment of system status, as
      well as research on integrated physiological responses, leading, for instance, to
      assessment of subject-specific susceptibility to POI or effects of cardiovascular
      alterations on muscular, vision and cognitive function. 

PMID- 23539441
TI  - Reply to the comment of Dr. Roy J. Shephard "A critique of RPE as a basis of
      exercise prescription".

PMID- 23539442
TI  - NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora
      A inhibitors: implications for treatment of metastatic solid tumors.
AB  - Aurora A kinase (AURKA) is overexpressed in 96% of human cancers and is
      considered an independent marker of poor prognosis. While the majority of tumors
      have elevated levels of AURKA protein, few have AURKA gene amplification,
      implying that posttranscriptional mechanisms regulating AURKA protein levels are
      significant. Here, we show that NEDD9, a known activator of AURKA, is directly
      involved in AURKA stability. Analysis of a comprehensive breast cancer tissue
      microarray revealed a tight correlation between the expression of both proteins,
      significantly corresponding with increased prognostic value. A decrease in AURKA,
      concomitant with increased ubiquitination and proteasome-dependent degradation,
      occurs due to depletion or knockout of NEDD9. Reexpression of wild-type NEDD9 was
      sufficient to rescue the observed phenomenon. Binding of NEDD9 to AURKA is
      critical for AURKA stabilization, as mutation of S296E was sufficient to disrupt
      binding and led to reduced AURKA protein levels. NEDD9 confers AURKA stability by
      limiting the binding of the cdh1-substrate recognition subunit of APC/C ubiquitin
      ligase to AURKA. Depletion of NEDD9 in tumor cells increases sensitivity to AURKA
      inhibitors. Combination therapy with NEDD9 short hairpin RNAs and AURKA
      inhibitors impairs tumor growth and distant metastasis in mice harboring
      xenografts of breast tumors. Collectively, our findings provide rationale for the
      use of AURKA inhibitors in treatment of metastatic tumors and predict the
      sensitivity of the patients to AURKA inhibitors based on NEDD9 expression.

PMID- 23539443
TI  - A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven
      colorectal tumor growth.
AB  - Most colorectal cancers (CRC) are initiated by mutations of APC, leading to
      increased beta-catenin-mediated signaling. However, continued requirement of
      Wnt/beta-catenin signaling for tumor progression in the context of acquired KRAS
      and other mutations is less well-established. To attenuate Wnt/beta-catenin
      signaling in tumors, we have developed potent and specific small-molecule
      tankyrase inhibitors, G007-LK and G244-LM, that reduce Wnt/beta-catenin signaling
      by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby
      promoting beta-catenin destabilization. We show that novel tankyrase inhibitors
      completely block ligand-driven Wnt/beta-catenin signaling in cell culture and
      display approximately 50% inhibition of APC mutation-driven signaling in most CRC
      cell lines. It was previously unknown whether the level of AXIN protein
      stabilization by tankyrase inhibition is sufficient to impact tumor growth in the
      absence of normal APC activity. Compound G007-LK displays favorable
      pharmacokinetic properties and inhibits in vivo tumor growth in a subset of APC
      mutant CRC xenograft models. In the xenograft model most sensitive to tankyrase
      inhibitor, COLO-320DM, G007-LK inhibits cell-cycle progression, reduces colony
      formation, and induces differentiation, suggesting that beta-catenin-dependent
      maintenance of an undifferentiated state may be blocked by tankyrase inhibition.
      The full potential of the antitumor activity of G007-LK may be limited by
      intestinal toxicity associated with inhibition of Wnt/beta-catenin signaling and
      cell proliferation in intestinal crypts. These results establish proof-of-concept
      antitumor efficacy for tankyrase inhibitors in APC-mutant CRC models and uncover
      potential diagnostic and safety concerns to be overcome as tankyrase inhibitors
      are advanced into the clinic.

PMID- 23539445
TI  - beta-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor
      signaling and predicts poor prognosis in lung adenocarcinoma.
AB  - Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression;
      however, the underlying mechanism for the self-renewal of cancer cells remains
      undefined. In the study, immunohistochemical analysis of specimens freshly
      excised from patients with lung adenocarcinoma showed that high expression of
      insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was
      positively correlated with the expressions of cancer stem cell markers CD133 and
      aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced
      POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like
      cells (LACSLC) through PI3K/AKT/GSK3beta/beta-catenin cascade. POU5F1 could form
      a novel complex with beta-catenin and SOX2 to bind Nanog promoter for
      transcription to maintain self-renewal of LACSLCs, which was dependent on the
      functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated
      LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo
      xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic
      potentials of LACSLCs. By analyzing pathologic specimens excised from 200
      patients with lung adenocarcinoma, we found that colocalization of highly
      expressed IGF-IR with beta-catenin and POU5F1 predicted poor prognosis. Taken
      together, we show that IGF-IR-mediated POU5F1 expression to form a complex with
      beta-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of
      LACSLCs, and the integrative clinical detection of the expressions of IGF-IR,
      beta-catenin, and POU5F1 is indicatory for predicting prognosis in the patients
      of lung adenocarcinoma.

PMID- 23539444
TI  - Collagen prolyl hydroxylases are essential for breast cancer metastasis.
AB  - The presence of hypoxia and fibrosis within the primary tumor are two major risk
      factors for metastasis of human breast cancer. In this study, we demonstrate that
      hypoxia-inducible factor 1 activates the transcription of genes encoding collagen
      prolyl hydroxylases that are critical for collagen deposition by breast cancer
      cells. We show that expression of collagen prolyl hydroxylases promotes cancer
      cell alignment along collagen fibers, resulting in enhanced invasion and
      metastasis to lymph nodes and lungs. Finally, we establish the prognostic
      significance of collagen prolyl hydroxylase mRNA expression in human breast
      cancer biopsies and show that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase
      inhibitor, decreases tumor fibrosis and metastasis in a mouse model of breast
      cancer.

PMID- 23539446
TI  - Elevated ALCAM shedding in colorectal cancer correlates with poor patient
      outcome.
AB  - Molecular biomarkers of cancer are needed to assist histologic staging in the
      selection of treatment, outcome risk stratification, and patient prognosis. This
      is particularly important for patients with early-stage disease. We show that
      shedding of the extracellular domain of activated leukocyte cell adhesion
      molecule (ALCAM) is prognostic for outcome in patients with colorectal cancer
      (CRC). Previous reports on the prognostic value of ALCAM expression in CRC have
      been contradictory and inconclusive. This study clarifies the prognostic value of
      ALCAM by visualizing ectodomain shedding using a dual stain that detects both the
      extracellular and the intracellular domains in formalin-fixed tissue. Using this
      novel assay, 105 patients with primary CRCs and 12 normal mucosa samples were
      evaluated. ALCAM shedding, defined as detection of the intracellular domain in
      the absence of the corresponding extracellular domain, was significantly elevated
      in patients with CRC and correlated with reduced survival. Conversely, retention
      of intact ALCAM was associated with improved survival, thereby confirming that
      ALCAM shedding is associated with poor patient outcome. Importantly, analysis of
      patients with stage II CRC showed that disease-specific survival is significantly
      reduced for patients with elevated ALCAM shedding (P = 0.01; HR, 3.0), suggesting
      that ALCAM shedding can identify patients with early-stage disease at risk of
      rapid progression.

PMID- 23539447
TI  - Fibroblast-specific protein 1/S100A4-positive cells prevent carcinoma through
      collagen production and encapsulation of carcinogens.
AB  - Stromal restraints to cancer are critical determinants of disease but they remain
      incompletely understood. Here, we report a novel mechanism for host surveillance
      against cancer contributed by fibroblast-specific protein 1 (FSP1)+ /S100A4+
      fibroblasts. Mechanistic studies of fibrosarcoma formation caused by subcutaneous
      injection of the carcinogen methylcholanthrene (MCA) had suggested that IFN-gamma
      receptor signaling may restrict MCA diffusion by inducing expression of collagen
      (foreign body reaction). We tested the hypothesis that this reaction encapsulated
      MCA and limited carcinogenesis by determining whether its ability to induce
      fibrosarcomas was impaired in the absence of proliferating fibroblasts. We found
      that FSP1+ /S100A4+ fibroblasts accumulated around the carcinogen where they
      produced collagens, encapsulating MCA and protecting epithelial cells from DNA
      damage. Ablation of these cells at the site of MCA injection by local
      administration of ganciclovir in FSP-TK transgenic mice altered tumor morphology
      to an epithelial phenotype, indicating that, in the absence of encapsulating
      fibroblasts, MCA targeted epithelial cells. Notably, we showed that destruction
      of the fibrous capsule around the MCA by local injection of collagenase induced
      rapid tumor development in mice that were otherwise durably tumor free. Our
      findings demonstrate that the FSP1+ /S100A4+ fibroblasts prevent epithelial
      malignancy and that collagen encapsulation of carcinogens protects against tumor
      development. Together, this study provides a novel mechanism for host
      surveillance against cancer.

PMID- 23539448
TI  - Androgen receptor-independent function of FoxA1 in prostate cancer metastasis.
AB  - FoxA1 (FOXA1) is a pioneering transcription factor of the androgen receptor (AR)
      that is indispensible for the lineage-specific gene expression of the prostate.
      To date, there have been conflicting reports on the role of FoxA1 in prostate
      cancer progression and prognosis. With recent discoveries of recurrent FoxA1
      mutations in human prostate tumors, comprehensive understanding of FoxA1 function
      has become very important. Here, through genomic analysis, we reveal that FoxA1
      regulates two distinct oncogenic processes via disparate mechanisms. FoxA1
      induces cell growth requiring the AR pathway. On the other hand, FoxA1 inhibits
      cell motility and epithelial-to-mesenchymal transition (EMT) through AR
      independent mechanism directly opposing the action of AR signaling. Using
      orthotopic mouse models, we further show that FoxA1 inhibits prostate tumor
      metastasis in vivo. Concordant with these contradictory effects on tumor
      progression, FoxA1 expression is slightly upregulated in localized prostate
      cancer wherein cell proliferation is the main feature, but is remarkably
      downregulated when the disease progresses to metastatic stage for which cell
      motility and EMT are essential. Importantly, recently identified FoxA1 mutants
      have drastically attenuated ability in suppressing cell motility. Taken together,
      our findings illustrate an AR-independent function of FoxA1 as a metastasis
      inhibitor and provide a mechanism by which recurrent FoxA1 mutations contribute
      to prostate cancer progression.

PMID- 23539449
TI  - Booster vaccinations against cancer are critical in prophylactic but detrimental
      in therapeutic settings.
AB  - Although cancer vaccines are in the clinic, several issues remain to be addressed
      to increase vaccine efficacy. In particular, whether how and how frequently a
      patient should be boosted remains to be defined. Here, we have assessed the
      ability of dendritic cell (DC)-based vaccines to induce a long-lasting tumor
      specific CTL response in either prophylactic or therapeutic settings by taking
      advantage of transplantable and spontaneous mouse tumor models. Implementing a 24
      hour ex vivo intracellular cytokine production assay, we have found that priming
      with a DC-based vaccine induced a long-lasting CTL response in wild-type mice,
      and homologous boosting better sustained the pool of central memory T cells,
      which associated with potent protection against B16F1 melanoma challenge.
      Appropriate timing of booster vaccination was also critical, as a tight boosting
      schedule hindered persistence of IFN-gamma-competent memory CD8(+) T cells and
      mice survival in prophylactic settings. Conversely, prime/boost vaccination
      proved to be of no advantage or even detrimental in therapeutic settings in B16F1
      and transgenic adenocarcinoma of the mouse prostate (TRAMP) models, respectively.
      Although DC priming was indeed needed for tumor shrinkage, restoration of immune
      competence, and prolonged survival of TRAMP mice, repeated boosting did not
      sustain the pool of central memory CTLs and was detrimental for mice overall
      survival. Thus, our results indicate that booster vaccinations impact antitumor
      immunity to different extents, depending on their prophylactic or therapeutic
      administration, and suggest evaluating the need for boosting in any given patient
      with cancer depending on the state of the disease.

PMID- 23539450
TI  - Genomic aberrations occurring in subsets of serrated colorectal lesions but not
      conventional adenomas.
AB  - A subset of aggressive colorectal cancers exhibit BRAF mutation, MLH1
      methylation, and a CpG island methylator phenotype (CIMP), but precursors are
      poorly established. In this study, we determined the status of these markers in
      colorectal polyps and evaluated associated risk factors. The study included 771
      polyp cases and 1,027 controls who were ages 24 to 80 years, part of a group
      health program, received a colonoscopy from 1998 to 2007, and completed a
      structured questionnaire assessing risk factors. Following standard pathology
      review, polyps were assayed for BRAF mutation (V600E) and tested for MLH1 and
      CIMP methylation, the latter including the genes, CACNA1G, IGF2, NEUROG1, RUNX3,
      and SOCS1. Polytomous logistic regression was used to estimate ORs and 95%
      confidence intervals for the association between molecularly defined subsets of
      polyps and potential risk factors. There were 580 conventional adenomas and 419
      serrated lesions successfully assayed. For adenomas, the prevalence of each
      marker was <=1%. In contrast, 55% of serrated lesions harbored mutant BRAF, 26%
      were CIMP-high, and 5% had methylated MLH1. In these lesions, the highest
      prevalence of markers was in sessile-serrated polyps (SSP) of >=10 mm that were
      in the right-side/cecal regions of the colon. Risk factors for CIMP-high-serrated
      lesions included Caucasian race, current smoking status, and a history of polyps,
      whereas for serrated lesions with mutant BRAF, the significant risk factors were
      male sex, current smoking status, obesity, and a history of polyps. Our results
      suggest that SSPs and other large, right-sided serrated lesions have a unique
      molecular profile that is similar to CIMP-high, BRAF-mutated colorectal cancers.

PMID- 23539452
TI  - Infection control for a methicillin-resistant Staphylococcus aureus outbreak in
      an advanced emergency medical service center, as monitored by molecular analysis.
AB  - A methicillin-resistant Staphylococcus aureus (MRSA) outbreak occurred in an
      advanced emergency medical service center between 2010 and 2011. Our objective
      was to evaluate the status of the MRSA outbreak, as monitored by molecular
      analysis. Twenty-eight MRSA strains were isolated from blood samples from 11
      patients, from other specimens (pharynx, nasal cavity, etc.) from 12 patients,
      from two environmental samples, and from the skin, middle nasal meatus, and urine
      of one patient each from other wards. Pulsed-field gel electrophoresis (PFGE) was
      performed to evaluate horizontal transmission. Molecular typing by PFGE showed
      that the 28 MRSA strains presented 7 patterns in total, and that 11 of the MRSA
      strains had the same PGFE pattern. Unselective use of intranasal mupirocin
      ointment, MRSA monitoring for new inpatients, and prevention of direct or
      indirect contact infection were performed. However, the number of inpatients with
      MRSA did not quickly decrease, and additional molecular typing by PFGE showed
      that 10 of 19 MRSA strains found (5 of 6 from blood, 5 of 13 from other
      specimens) were the same as those found previously. Lectures and ward rounds were
      performed repeatedly, and staff participation in ward rounds was suggested.
      Finally, the number of inpatients with MRSA significantly decreased more than 6
      months after the intervention. Although the MRSA outbreak was thought to have
      ended, follow-up molecular typing by PFGE showed that horizontal transmission
      persisted. Our data suggest that various combinations of infection control
      measures are essential when dealing with an MRSA outbreak, and monitoring by
      molecular analysis using PFGE is useful to identify the status of the outbreak. 

PMID- 23539451
TI  - Endothelial cell protein C receptor opposes mesothelioma growth driven by tissue
      factor.
AB  - The procoagulant protein tissue factor (F3) is a powerful growth promoter in many
      tumors, but its mechanism of action is not well understood. More generally, it is
      unknown whether hemostatic factors expressed on tumor cells influence tissue
      factor-mediated effects on cancer progression. In this study, we investigated the
      influence of tissue factor, endothelial cell protein C receptor (EPCR, PROCR),
      and protease activated receptor-1 (PAR1, F2R) on the growth of malignant pleural
      mesothelioma (MPM), using human MPM cells that lack or express tissue factor,
      EPCR or PAR1, and an orthotopic nude mouse model of MPM. Intrapleural
      administration of MPM cells expressing tissue factor and PAR1 but lacking EPCR
      and PAR2 (F2RL1) generated large tumors in the pleural cavity. Suppression of
      tissue factor or PAR1 expression in these cells markedly reduced tumor growth. In
      contrast, tissue factor overexpression in nonaggressive MPM cells that expressed
      EPCR and PAR1 with minimal levels of tissue factor did not increase their limited
      tumorigenicity. More importantly, ectopic expression of EPCR in aggressive MPM
      cells attenuated their growth potential, whereas EPCR silencing in nonaggressive
      MPM cells engineered to overexpress tissue factor increased their tumorigenicity.
      Immunohistochemical analyses revealed that EPCR expression in tumor cells reduced
      tumor cell proliferation and enhanced apoptosis. Overall, our results enlighten
      the mechanism by which tissue factor promotes tumor growth through PAR1, and they
      show how EPCR can attenuate the growth of tissue factor-expressing tumor cells.

PMID- 23539453
TI  - Loop-mediated isothermal amplification (LAMP): recent progress in research and
      development.
AB  - Loop-mediated isothermal amplification (LAMP) is an established technology that
      continues to attract the attention of researchers in many fields. Research and
      development efforts on LAMP technology in recent years have focused on two major
      areas; first, the study of its clinical application as an approved in vitro
      diagnostics tool in Japan and certain other countries; and second, research aimed
      at further simplifying the LAMP test process. This review provides an overview of
      the status of LAMP on these two topics by summarizing research work conducted, in
      the main, after our previous review article.

PMID- 23539454
TI  - Plants regenerated from tissue culture contain stable epigenome changes in rice.
AB  - Most transgenic crops are produced through tissue culture. The impact of
      utilizing such methods on the plant epigenome is poorly understood. Here we
      generated whole-genome, single-nucleotide resolution maps of DNA methylation in
      several regenerated rice lines. We found that all tested regenerated plants had
      significant losses of methylation compared to non-regenerated plants. Loss of
      methylation was largely stable across generations, and certain sites in the
      genome were particularly susceptible to loss of methylation. Loss of methylation
      at promoters was associated with deregulated expression of protein-coding genes.
      Analyses of callus and untransformed plants regenerated from callus indicated
      that loss of methylation is stochastically induced at the tissue culture step.
      These changes in methylation may explain a component of somaclonal variation, a
      phenomenon in which plants derived from tissue culture manifest phenotypic
      variability. DOI:http://dx.doi.org/10.7554/eLife.00354.001.

PMID- 23539455
TI  - Unilateral acute idiopathic maculopathy in a 14-year-old Hispanic girl.
AB  - INTRODUCTION: The authors discuss a case of unilateral diminished vision in a 14
      year-old Hispanic girl. METHODS: Retrospective chart review. RESULTS: The patient
      was referred to University Hospital (UH) at New Jersey Medical School with a
      complaint of blurry vision in the right eye for approximately 1 month. Clinical
      examination showed a yellow-gray area of retinal pigment epithelium (RPE)
      elevation in the perifoveal region OD and normal examination OS. Optical
      coherence tomography showed a corresponding area of RPE elevation with associated
      sub-RPE fluid. Fluorescein angiogram on presentation disclosed a focal area of
      hyperfluorescence and dye pooling. Bloodwork and chest x-ray were within normal
      limits. These changes resolved over the ensuing 4 weeks despite discontinuation
      of all treatment. The patient experienced complete resolution of her symptoms.
      CONCLUSION: We report a case of unilateral acute idiopathic maculopathy in a 14
      year-old Hispanic girl. To the authors' knowledge, this is the youngest reported
      patient with this condition to date.

PMID- 23539456
TI  - Primary vitrectomy for the treatment of retinal detachment in highly myopic eyes
      with axial length over 30 mm.
AB  - OBJECTIVE: To assess the functional and anatomical outcome of primary vitrectomy
      without scleral buckling for rhegmatogenous retinal detachment (RRD) in highly
      myopic eyes with axial length over 30 mm. METHODS: In this retrospective,
      interventional case series, we evaluated the outcome of primary vitrectomy
      without scleral buckling in 67 highly myopic patients (67 eyes) with RRD.
      Anatomical success rate was defined as complete reattachment of the retina
      without definitive silicone oil tamponade. RESULTS: Retinal reattachment was
      achieved with a single surgery in 49 of 67 eyes (73.1%) and after 2 or 3
      surgeries in 54 eyes (80.6%). The characteristics of retinal tears did not
      influence the final outcome. Multivariate analysis revealed that a longer axial
      length was the only factor associated with a higher failure rate, p = 0.0061.
      Mean preoperative visual acuity significantly increased after surgery, p =
      0.0003. CONCLUSION: The study demonstrated fair efficacy of vitrectomy and fluid
      gas exchange in the treatment of retinal detachment in highly myopic eyes with an
      axial length over 30 mm.

PMID- 23539457
TI  - Discomfort symptoms reduction and ocular surface parameters recovery with Artelac
      Rebalance treatment in mild-moderate dry eye.
AB  - PURPOSE: To evaluate Artelac Rebalance(r) eyedrops' efficacy in symptoms
      reduction, ocular surface parameters recovery, and tolerability in the treatment
      of mild to moderate dry eye. METHODS: Fifteen patients were enrolled. Inclusion
      criteria were Ocular Surface Disease Index (OSDI) score >16, tear film break-up
      time (TFBUT) <10 seconds, Schirmer test I >10 mm/5 min, and mild ocular surface
      damage (Oxford grading) <=3. Artelac Rebalance(r) eyedrops were administered 3
      times daily for 2 months. Patients were evaluated at enrollment, after 2 days of
      washout (baseline), and after 1 and 2 months of treatment. Parameters for ocular
      discomfort (OSDI score), tear film quality (Schirmer test I, TFBUT, tear
      osmolarity), ocular surface damage (fluorescein staining, conjunctival imprint
      cytology), and inflammation (scraping cytology and exuded serum albumin) were
      measured. Tolerability and satisfaction were assessed by validated
      questionnaires. RESULTS: At endpoint versus baseline, all variables showed a
      statistically significant improvement (paired Student t test, p<0.01 for all
      parameters) as follows: OSDI score (21.9 +/- 10.6 vs 35.8 +/- 12.2), TFBUT (6.5
      +/- 1.1 s vs 5.2 +/- 2.3 s), Oxford grading of corneal and conjunctival damage
      (0.56 +/- 0.50 vs 1.16 +/- 0.37), tear osmolarity (294.6 +/- 2.1 mOsm/L vs 303.1
      +/- 4.6 mOsm/L), conjunctival goblet cell density/mm2 (140.8 +/- 43.3 cells/mm2
      vs 115.1 +/- 15.8 cells/mm2), scraping cytology score (2.9 +/- 1.0 vs 4.2 +/-
      1.3), and percentage of serum albumin in tears (9.2% +/- 4.8% vs 24.1% +/-
      10.8%). Tolerability and satisfaction were scored high, with no adverse events
      reported. CONCLUSIONS: Application of Artelac Rebalance(r) eyedrops for 2 months
      in mild to moderate dry eye resulted in a reduction of ocular inflammation
      parameters, ocular surface damage, and subjective discomfort symptoms, with a
      parallel improvement in tear film quality (measured by TFBUT and osmolarity).

PMID- 23539458
TI  - Modified method of sutureless intrascleral posterior chamber intraocular lens
      fixation without capsular support.
AB  - PURPOSE: This study reports the clinical results of sutureless intrascleral
      fixation of posterior chamber intraocular lenses (PC IOLs) in eyes without
      capsular support.? METHODS: Thirty patients without capsular support who
      underwent standard 3-piece foldable PC IOL implantation using the sutureless
      intrascleral fixation technique were studied retrospectively. Folded PC IOLs were
      injected through corneal incisions, with 2 haptics piercing out from 2
      corresponding scleral punctures, which were 1.5 mm from the limbus and exactly
      180 degrees  to each other, and then 2 haptics piercing respectively were placed
      in 2 corresponding limbus-parallel intrascleral tunnels. All patients were
      evaluated for preoperative and postoperative status and complications.? RESULTS:
      During the follow-up period, the visual acuity of all 30 patients significantly
      improved, with that of 21 patients improving by more than 0.6. The intraocular
      pressures of all patients were stable. All PC IOLs were stable and centered.
      Optical coherence tomography revealed that the haptics were located within the
      tunnel. Other complications, such as IOL dislocation, endophthalmitis, and
      retinal detachment, were not detected.? CONCLUSION: Sutureless intrascleral
      fixation is safe and effective for the implantation of PC IOLs in eyes without
      capsular support from a variety of causes.

PMID- 23539459
TI  - Effect of VEGF and anti-VEGF compounds on retinal pigment epithelium
      permeability: an in vitro study.
AB  - OBJECTIVE: To evaluate the effect of 2 vascular endothelial growth factor (VEGF)
      isoforms (121 and 165) and 2 anti-VEGF compounds (ranibizumab and pegaptanib
      sodium) on the permeability of human retinal pigment epithelium (RPE) cells in
      vitro.? METHODS: The RPE permeability was assessed on ARPE19 cells grown onto
      inserts of polytetrafluoroethylene previously treated with ammonia gas plasma.
      Paracellular permeability to ions was measured by mean of transepithelial
      electrical resistance (TEER). Permeability to non-ionic molecules was gathered by
      the amount of fluorescein dextran (FD) passing across the monolayer within 2
      hours.? RESULTS: Only VEGF165 applied at the apical side of the monolayer induced
      a statistically significant decrease of TEER (p<0.001). No changes in TEER were
      observed when pegaptanib sodium or ranibizumab were apically administered
      together with VEGF165. ?Both VEGF isoforms significantly increased permeability
      to 4 kDa dextran (p<0.01). Apical administration of ranibizumab or pegaptanib
      sodium as well as coadministration of pegaptanib sodium with VEGF121 or VEGF165
      induced a statistically significant increase of permeability to 4 kDa FD. ?
      CONCLUSION: Both VEGF isoforms and anti-VEGF compounds exert an effect on human
      RPE permeability in vitro.

PMID- 23539460
TI  - Evaluation of macular thickness after uncomplicated cataract surgery using
      optical coherence tomography.
AB  - PURPOSE: To evaluate central macular thickness (CMT) after cataract surgery in
      selected groups of patients. ? METHODS: The study comprised 4 groups-patients
      with epiretinal membrane, patients with high myopia, patients with diabetes
      without retinopathy, and healthy subjects-who underwent phacoemulsification and
      intraocular lens implantation. Central macular thickness was measured with
      spectral domain optical coherence tomography (OCT) using the 3D macular cube
      scan. The OCT evaluation was performed preoperatively and 1, 6, 15, 30, 60, 90,
      and 360 days after surgery. Visual acuity was measured preoperatively and after 6
      and 360 days after surgery.? RESULTS: The study included 258 patients, 164 women
      and 94 men, with a mean age of 74 (SD 7.6) years. A statistically significant
      increase in CMT was observed from day 30 in patients with epiretinal membrane (p
      = 0.010) and diabetic patients (p = 0.026), reaching its maximum thickness at day
      60 (p = 0.001 and p = 0.001), while it was observed only on day 360 in healthy
      subjects (p = 0.018) and those with high myopia (p = 0.003). The correlation
      between CMT and visual acuity was statistically significant only in the diabetic
      group (r = 0.61, p<0.01).? CONCLUSIONS: Following cataract surgery, CMT changes
      according to characteristic patterns in the different groups studied. These
      changes did not prevent an optimal recovery of visual function.

PMID- 23539461
TI  - Does beta-ray emitting therapy of ciliary body tumors decrease central corneal
      endothelial cell density.
AB  - PURPOSE: To evaluate the effect of plaque radiation therapy using beta
      radioactive isotope for anterior segment tumors on the density and morphology of
      endothelial cells. ? METHODS: Endothelial cell density (ECD) and morphometry in
      15 eyes of 15 patients with ciliary body tumor was examined prior to and 6 months
      after radiation therapy. After irradiation, central ECD values were also compared
      with peripheral (2.0 mm from limbus) ECD values measured around the plaque. The
      ECD, average cell area, coefficient of variation of cell area, and pachymetry
      measurements were conducted with contact specular microscopy.? RESULTS: The mean
      corrected ECD values prior to irradiation were 2147 +/- 128 cells/mm2 and 2050 +/
      108 cells/mm2 after the radiation therapy. After irradiation, the mean
      peripheral ECD values were 2056 +/- 101 cells/mm2. A significant decrease in ECD
      values was observed after radiation (p = 0.007). Peripheral ECD values measured
      around the plaque showed no significant difference (p = 0.86) as compared to
      central ECD values.? CONCLUSIONS: According to our measurements, plaque therapy
      for tumors in the anterior segment decreases ECD significantly, but not highly,
      even in case of plaques containing beta-radiation isotope, and the plaques are
      not placed direct on the cornea surface. The decreased ECD causes no changes in
      corneal thickness or transparency, but it may have an influence on a subsequent
      cataract surgery, which generates further endothelial loss.

PMID- 23539462
TI  - Endothelial cells and central corneal thickness after modified sutureless manual
      small-incision cataract surgery.
AB  - PURPOSE: Manual small-incision cataract surgery (MSICS) is a viable method for
      cataract surgery around the world. We evaluated the impact of a modification of
      MSICS, in which an anterior chamber maintainer is used throughout the surgery
      with the addition of ocular viscoelastic device prior to nucleus removal (M
      MSICS), on the corneal endothelium.? METHODS: This prospective study comprised
      patients randomly assigned for cataract surgery who underwent M-MSICS. Patients
      underwent corneal endothelial counts by a noncontact specular microscopy in the
      center and at 12 and 6 o'clock position as well as central corneal pachymetry
      (CCT) preoperatively, and at 1 week and 1 and 3 months postoperatively. ?
      RESULTS: Twenty-one eyes were included, 16 of which completed the entire follow
      up. There was a statistically significant difference in endothelial cell loss at
      the center of the cornea at 1 week postoperatively (p = 0.003). However, there
      was no significant difference in endothelial cell measurements between
      preoperative and other postoperative timepoints at the center of the cornea. In
      addition, no significant difference was found in the 12 and 6 o'clock
      measurements at all timepoints. There was a mild but statistically significant
      increase in CCT at the center of the cornea at 1-week and 1-month postoperative
      measurements as compared to preoperative measurement (p<0.05). By postoperative
      month 3, CCT had returned to baseline level. ? CONCLUSIONS: Modified MSICS offers
      a viable enhancement of MSICS, with mild and transient impact on the corneal
      endothelial cell density and corneal pachymetry.

PMID- 23539463
TI  - Corneal biomechanical properties and their correlates with healing process after
      Descemetic versus ?pre-Descemetic lamellar keratoplasty.
AB  - Purpose: To evaluate the influence of the wound-healing process on corneal
      biomechanics in patients after 2 types of deep anterior lamellar keratoplasty:
      Descemetic with total stromal resection vs pre-Descemetic with deep stromal
      dissection.?Methods: This prospective comparative study consisted of 32 eyes of
      32 patients. Patients were divided into 2 groups: Descemetic (17 eyes) and pre
      Descemetic (15 eyes). Reichert ocular response analyzer was used to measure
      corneal hysteresis (CH) and corneal resistance factor (CRF) at 1 and 3 months
      postoperatively. Central corneal thickness (CCT) was measured using ultrasonic
      pachymetry. In vivo confocal microscopy was also used to study the corneal wound
      healing process and to correlate these events with the corneal biomechanics
      postoperatively in both groups.?Results: Both mean CH and mean CRF were
      significantly lower in the Descemetic than the pre-Descemetic group at 1 and 3
      months postoperatively (p<0.0001). The reflectivity of activated keratocytes at
      both the interface and wound edge was less in the Descemetic than the pre
      Descemetic group at all times as revealed by the confocal microscopy. No
      statistically significant difference in mean CCT was found between both groups at
      1 and 3 months. Subsequent and progressive decrease in interface reflectivity of
      activated keratocytes was presented in both groups.?Conclusions: Healing process
      at the interface is key to optimal corneal integrity. In the pre-Descemetic
      group, stroma-to-stroma healing stimulated more activated keratocytes and hence
      stronger healing response, providing superior corneal biomechanics. Significant
      positive correlation between the intensity of the keratocyte activation and
      corneal integrity was found.

PMID- 23539464
TI  - Outcomes of conjunctival compression sutures for hypotony after glaucoma
      filtering surgery.
AB  - OBJECTIVE: To evaluate the outcomes of conjunctival compression sutures (CCS) for
      enlarged overfiltering blebs associated with ocular hypotony after uncomplicated
      trabeculectomy with mitomycin C (TM). METHODS: A retrospective analysis of
      consecutively recruited patients with enlarged conjunctival bleb associated with
      hypotony who had undergone CCS was performed. Patients were considered for CCS if
      they had enlarged overfiltering bleb for at least 4 weeks, following an
      uncomplicated TM, with no sign of resolution. Only patients with hypotony,
      defined as intraocular pressure (IOP) <6 mm Hg associated with a reduced vision
      of at least 2 lines, were included. Success was defined as an IOP ?>6 mm Hg 6
      months after surgery. RESULTS: A total of 45 eligible patients were identified.
      In 29 eyes of 45 patients (64.4%), success in providing resolution of the
      preexisting hypotony (postoperative IOP mean +/- standard deviation 13.4 +/- 1.8
      mm Hg, range 10-16 mm Hg) was obtained. Out of these 29 eyes, 9 eyes had a
      conjunctival bleb diffusion over 180 degrees, 19 eyes overfiltering bleb over 270
      degrees, and 1 eye over 360 degrees. Complications from CCS included a transient
      spike of IOP in the first postoperative week (8 patients); a bleb rupture
      associated with conjunctival leaks and hypotony was observed in one eye.
      CONCLUSIONS: The placement of CCS is a safe and effective technique for managing
      overfiltering blebs associated with hypotony. The present study suggests that CCS
      are not effective for dealing with circumferential blebs extending over 360
      degrees.

PMID- 23539465
TI  - Antipsychotic and psychostimulant drug combination therapy in attention
      deficit/hyperactivity and disruptive behavior disorders: a systematic review of
      efficacy and tolerability.
AB  - This systematic review examines treatment guidelines, efficacy/effectiveness, and
      tolerability regarding the use of antipsychotics concurrently with
      psychostimulants in treating aggression and hyperactivity in children and
      adolescents. Articles examining the concurrent use of antipsychotics and
      psychostimulants to treat comorbid attention deficit/hyperactivity disorder
      (ADHD) and disruptive behavior disorders (DBDs) were identified and their results
      were summarized and critically analyzed. Antipsychotic and stimulant combination
      therapy is recommended by some guidelines, but only as a third-line treatment
      following stimulant monotherapy and stimulants combined with behavioral
      interventions to treat aggression in patients with ADHD. Some studies suggest
      efficacy/effectiveness for an antipsychotic and stimulant combination in the
      treatment of aggression and hyperactivity in children and adolescents. However,
      the data do not clearly demonstrate superiority compared to antipsychotic or
      psychostimulant monotherapy. Most studies were performed over short time periods,
      several lacked blinding, few studies used any placebo control, and no comparisons
      were made with behavioral interventions. There are concerns about the
      tolerability of combination therapy, but data do not suggest significantly worse
      adverse effects for combination compared to either antipsychotic or stimulant
      monotherapy. Conversely, and contrary to speculation, use of a stimulant does not
      significantly reduce metabolic effects of antipsychotics. Combination treatment
      with antipsychotics and psychostimulants is used frequently, and increasingly
      more often. Few studies have directly examined this combination for the treatment
      of ADHD and DBDs. Further studies are necessary to confirm the efficacy and
      tolerability of the concurrent use of antipsychotics and psychostimulants in
      children and adolescents.

PMID- 23539466
TI  - Self-rated health and life satisfaction among Canadian adults: associations of
      perceived weight status versus BMI.
AB  - PURPOSE: Obesity is associated with impaired health-related quality of life
      (HRQL). As perceived constructs, self-rated health (SRH) and general life
      satisfaction (LS) might be more strongly related to perceived weight status than
      actual weight status. The aim was to assess agreement between perceived weight
      status and self-reported body mass index (BMI), and to investigate their
      associations with SRH and LS as indicators of HRQL. METHODS: Cross-sectional data
      included 87,545 adults aged 18-65 years from the 2005 Canadian Community Health
      Survey. Agreement between perceived weight status and self-reported BMI was
      assessed. Prevalence of suboptimal SRH and LS was estimated by perceived weight
      status and BMI, and adjusted logistic regression used to assess the odds of
      suboptimal outcomes. RESULTS: Overall agreement between perceived weight status
      and self-reported BMI was only moderate (females: kappa = 0.58; males: kappa =
      0.42). The lowest prevalences of suboptimal SRH and LS were in those who reported
      both a healthy weight BMI and "about right" weight perception. Discordance
      between perceived weight status and BMI status, and congruence (i.e. perceived
      weight status = BMI) around underweight or overweight/obese were associated with
      poorer SRH and LS. For weight perceptions of "about right", BMI status had
      minimal influence on suboptimal SRH or LS, while perceptions of underweight or
      overweight were associated with higher odds of suboptimal SRH and LS, independent
      of BMI. CONCLUSIONS: Adults' weight status perceptions often do not agree with
      their actual weight status, even when self-reported. While both perceived and
      actual weight status influence self-rated health and life satisfaction,
      perceptions are more strongly associated with these HRQL indicators and should be
      considered when informing obesity-targeted policies and programmes.

PMID- 23539467
TI  - Mindfulness: a systematic review of instruments to measure an emergent patient
      reported outcome (PRO).
AB  - PURPOSE: Mindfulness has emerged as an important health concept based on evidence
      that mindfulness interventions reduce symptoms and improve health-related quality
      of life. The objectives of this study were to systematically assess and compare
      the properties of instruments to measure self-reported mindfulness. METHODS: Ovid
      Medline((r)), CINAHL((r)), and PsycINFO((r)) were searched through May 2012, and
      articles were selected if their primary purpose was development or evaluation of
      the measurement properties (validity, reliability, responsiveness) of a self
      report mindfulness scale. Two reviewers independently evaluated the
      methodological quality of the selected studies using the COnsensus-based
      Standards for the selection of health status Measurement INstruments checklist.
      Discrepancies were discussed with a third reviewer and scored by consensus.
      Finally, a level of evidence approach was used to synthesize the results and
      study quality. RESULTS: Our search strategy identified a total of 2,588 articles.
      Forty-six articles, reporting 79 unique studies, met inclusion criteria. Ten
      instruments quantifying mindfulness as a unidimensional scale (n = 5) or as a set
      of 2-5 subscales (n = 5) were reviewed. The Mindful Attention Awareness Scale was
      evaluated by the most studies (n = 27) and had positive overall quality ratings
      for most of the psychometric properties reviewed. The Five Facet Mindfulness
      Questionnaire received the highest possible rating ("consistent findings in
      multiple studies of good methodological quality") for two properties, internal
      consistency and construct validation by hypothesis testing. However, none of the
      instruments had sufficient evidence of content validity. Comprehensiveness of
      construct coverage had not been assessed; qualitative methods to confirm
      understanding and relevance were absent. In addition, estimates of test-retest
      reliability, responsiveness, or measurement error to guide users in protocol
      development or interpretation of scores were lacking. CONCLUSIONS: Current
      mindfulness scales have important conceptual differences, and none can be
      strongly recommended based solely on superior psychometric properties. Important
      limitations in the field are the absence of qualitative evaluations and accepted
      external referents to support construct validity. Investigators need to proceed
      cautiously before optimizing any mindfulness intervention based on the existing
      scales.

PMID- 23539468
TI  - Mapping CushingQOL scores to EQ-5D utility values using data from the European
      Registry on Cushing's syndrome (ERCUSYN).
AB  - PURPOSE: To construct a model to predict preference-adjusted EuroQol 5D (EQ-5D)
      health utilities for CS using the disease-specific health-related quality of life
      measure (CushingQOL). METHODS: Data were obtained from the European Registry on
      CS (ERCUSYN). ERCUSYN is a web-based, multicenter, observational study that
      enrolled 508 CS patients from 36 centers in 23 European countries. Patients
      included in the study completed both the EQ-5D and the disease-specific
      CushingQOL questionnaire. Socio-demographic and clinical data were also
      collected. The UK tariff values were used to calculate EQ-5D utility scores.
      Various predictive models were tested, and the final model was selected based on
      four criteria: explanatory power (adjusted R-squared), consistency of estimated
      coefficients (sign and parameter estimation), normality of prediction errors
      (mean error, mean absolute error, root mean squared error), and parsimony.
      RESULTS: For the mapping analysis, data were available from a total of 129
      patients. Mean (SD) age was 43.1 (13) years, and the sample was predominantly
      female (84.5 %). Patients had a mean (SD) CushingQOL score of 39.7 (17.1) and a
      mean (SD) 'tariff' value on the EQ-5D of 0.55 (0.3). The model which best met the
      criteria for selection included the intercept and 3 CushingQOL's questions and
      had an R(2) of 0.506 and a root mean square error of 0.216. CONCLUSIONS: It was
      possible to find a mapping function which successfully predicted the EQ-5D UK
      utilities from disease-specific CushingQOL scores. The function may be useful in
      calculating EQ-5D scores when EQ-5D data have not been gathered directly in a
      study.

PMID- 23539469
TI  - Development of a crosswalk for pain interference measured by the BPI and PROMIS
      pain interference short form.
AB  - INTRODUCTION: To help researchers in multiple sclerosis (MS) take advantage of
      the measurement properties of the PROMIS Pain Interference instrument while
      maintaining continuity with previous research, we developed and tested a
      crosswalk table to transform Brief Pain Inventory pain interference scale (BPI
      PI) scores to PROMIS-PI short form (PROMIS-PI SF) scores. METHODS: The BPI-PI and
      the PROMIS-PI SF were administered in two studies that included persons with MS.
      One sample of 369 participants served as a developmental calibration sample, and
      a separate sample of 360 served as a validation sample. The crosswalk development
      included dimensionality assessment, item-level parameter estimation, and
      assessment of accuracy. BPI-PI and PROMIS-PI T scores were obtained from
      participants' item responses, and using the crosswalk table, PROMIS-PI T scores
      were derived from responses to the BPI-PI items. Differences between observed and
      crosswalked T scores were compared in both samples. RESULTS: For BPI-PI summary
      scores ranging from 0 to 10, corresponding T scores ranged from 38.6 to 81.2. The
      mean difference between observed and crosswalked T scores was 0.51 (SD = 3.9) in
      the calibration sample and -1.47 (SD = 4.2) in the validation sample.
      Approximately 80 % of crosswalked scores in the calibration sample were within
      four score points of the observed PROMIS-PI SF scores, and 70 % were within four
      points in the validation sample. In both samples, the largest differences were at
      lower levels of the pain interference continuum. CONCLUSIONS: Crosswalked pain
      interference scores adequately approximated observed PROMIS-PI SF scores in both
      the calibration and validation samples. MS researchers and clinicians interested
      in adopting the PROMIS instruments can use this table to transform BPI-PI scores
      to enable comparisons with other studies and to maintain continuity with previous
      research.

PMID- 23539470
TI  - Direct and indirect abortion in the Roman Catholic tradition: a review of the
      Phoenix case.
AB  - In Roman Catholic Moral Theology, a direct abortion is never permitted. An
      indirect abortion, in which a life threatening pathology is treated, and the
      treatment inadvertently leads to the death of the fetus, may be permissible in
      proportionately grave situations. In situations in which a mother's life is
      endangered by the pregnancy before the fetus is viable, there is some debate
      about whether the termination of the pregnancy is a direct or indirect abortion.
      In this essay a recent case from a Roman Catholic sponsored hospital in Phoenix
      is reviewed along with the justifications for and arguments against viewing the
      pregnancy termination as an indirect abortion. After review of several arguments
      on both sides of the debate, it is concluded that termination of the pregnancy
      itself as the means of saving the mother cannot be considered an indirect
      abortion and that the principle of "double effect" does not justify the
      termination. In addition, the importance of a breakdown in communication between
      the local bishop and the administration of the hospital is shown to have
      contributed to the ultimate loss of Catholic sponsorship of the hospital.

PMID- 23539471
TI  - Classification via Bayesian Nonparametric Learning of Affine Subspaces.
AB  - It has become common for data sets to contain large numbers of variables in
      studies conducted in areas such as genetics, machine vision, image analysis and
      many others. When analyzing such data, parametric models are often too inflexible
      while nonparametric procedures tend to be non-robust because of insufficient data
      on these high dimensional spaces. This is particularly true when interest lies in
      building efficient classifiers in the presence of many predictor variables. When
      dealing with these types of data, it is often the case that most of the
      variability tends to lie along a few directions, or more generally along a much
      smaller dimensional submanifold of the data space. In this article, we propose a
      class of models that flexibly learn about this submanifold while simultaneously
      performing dimension reduction in classification. This methodology, allows the
      cell probabilities to vary nonparametrically based on a few coordinates expressed
      as linear combinations of the predictors. Also, as opposed to many black-box
      methods for dimensionality reduction, the proposed model is appealing in having
      clearly interpretable and identifiable parameters which provide insight into
      which predictors are important in determining accurate classification boundaries.
      Gibbs sampling methods are developed for posterior computation, and the methods
      are illustrated using simulated and real data applications.

PMID- 23539472
TI  - Multiple degradation pathways of phenanthrene by Stenotrophomonas maltophilia C6.
AB  - Stenotrophomonas maltophilia strain C6, capable of utilizing phenanthrene as a
      sole source of carbon and energy, was isolated from creosote-contaminated sites
      at Hilo, Hawaii. Twenty-two metabolites of phenanthrene, covering from
      dihydrodiol to protocatechuic acid, were isolated and characterized. Phenanthrene
      was degraded via an initial dioxygenation on 1,2-, 3,4-, and 9,10-C, where the
      3,4-dioxygenation and subsequent metabolisms were most dominant. The metabolic
      pathways were further branched by ortho- and meta-cleavage of phenanthrenediols
      to produce 1-hydroxy-2-naphthoic acid, 2-hydroxy-1-naphthoic acid, and
      naphthalene-1,2-dicarboxylic acid. These intermediates were then transformed to
      naphthalene-1,2-diol. 1-Hydroxy-2-naphthoic acid was also degraded via a direct
      ring cleavage. Naphthalene-1,2-diol underwent primarily ortho-cleavage to produce
      trans-2-carboxycinnamic acid and then to form phthalic acid, 4,5
      dihydroxyphthalic acid and protocatechuic acid. Accumulation of salicylic acid in
      prolonged incubation indicated that a limited extent of meta-cleavage of
      naphthalene-1, 2-diol also occurred. This is the first study of detailed
      phenanthrene metabolic pathways by Stenotrophomonas maltophilia.

PMID- 23539473
TI  - Effective concentration-based serum pharmacodynamics for antifungal azoles in a
      murine model of disseminated Candida albicans infection.
AB  - An assessment of the effective in vivo concentrations of antifungal drugs is
      important in determining their pharmacodynamics, and therefore, their optimal
      dosage regimen. Here we establish the effective in vivo concentration-based
      pharmacodynamics of three azole antifungal drugs (fluconazole, itraconazole, and
      ketoconazole) in a murine model of disseminated Candida albicans infection. A key
      feature of this study was the use of a measure of mycelial (m) growth rather than
      of yeast growth, and pooled mouse sera rather than synthetic media as a growth
      medium, for determining the minimum inhibitory concentrations (MICs) of azoles
      for C. albicans (denoted serum mMICs). The serum mMIC assay was then used to
      measure antifungal concentrations and effects as serum antifungal titers in the
      serum of treated mice. Both serum mMIC and sub-mMIC values reflected the
      effective in vivo serum concentrations. Supra-mMIC and mMIC effects exhibited
      equivalent efficacies and were concentration-independent, while the sub-mMIC
      effect was concentration-dependent. Following administration of the minimum drug
      dosage that inhibited an increase in mouse kidney fungal burden, the duration
      periods of these effects were similar for all drugs tested. The average duration
      of either the mMIC effect including the supra-mMIC effect, the sub-mMIC effect,
      or the post-antifungal effect (PAFE) were 6.9, 6.5 and 10.6 h, respectively. Our
      study suggests that the area under the curve for serum drug concentration versus
      time, between the serum mMIC and the sub-mMIC, and exposure time above the serum
      sub-mMIC after the mMIC effect, are major pharmacodynamic parameters. These
      findings have important implications for effective concentration-based
      pharmacodynamics of fungal infections treated with azoles.

PMID- 23539474
TI  - Dietary fiber, organic acids and minerals in selected wild edible fruits of
      Mozambique.
AB  - The harvesting, utilization and marketing of indigenous fruits and nuts have been
      central to the livelihoods of the majority of rural communities in African
      countries. In this study we report on the content of dietary fiber, minerals and
      selected organic acids in the pulps and kernels of the wild fruits most commonly
      consumed in southern Mozambique. The content of soluble fiber in the pulps ranged
      from 4.3 to 65.6 g/100 g and insoluble fiber from 2.6 to 45.8 g/100 g. In the
      kernels the content of soluble fiber ranged from 8.4 to 42.6 g/100 g and
      insoluble fiber from 14.7 to 20.9 g/100 g. Citric acid was found in all fruits up
      to 25.7 g/kg. The kernels of Adansonia digitata and Sclerocarya birrea were shown
      to be rich in calcium, iron, magnesium and zinc. The data may be useful in
      selecting wild fruit species appropriate for incorporation into diets. 

PMID- 23539476
TI  - Imaging cardiac fat.
AB  - Ectopic fat deposition has been associated with lipotoxicity and derangement in
      local and systemic metabolism, insulin resistance, cardiac dysfunction,
      atherosclerosis, local, and systemic inflammation. The mechanisms and potentially
      detrimental effects of such an accumulation should be fully investigated in order
      to establish preventive strategies. The aim of this review is to provide an
      overview of current knowledge regarding imaging techniques to measure cardiac fat
      deposition and its potential clinical relevance, if any.

PMID- 23539475
TI  - Molecular basis of the dopaminergic system in the cricket Gryllus bimaculatus.
AB  - In insects, dopamine modulates various aspects of behavior such as learning and
      memory, arousal and locomotion, and is also a precursor of melanin. To elucidate
      the molecular basis of the dopaminergic system in the field cricket Gryllus
      bimaculatus DeGeer, we identified genes involved in dopamine biosynthesis, signal
      transduction, and dopamine re-uptake in the cricket. Complementary DNA of two
      isoforms of tyrosine hydroxylase (TH), which convert tyrosine into L-3,4
      dihydroxyphenylalanine, was isolated from the cricket brain cDNA library. In
      addition, four dopamine receptor genes (Dop1, Dop2, Dop3, and DopEcR) and a high
      affinity dopamine transporter gene were identified. The two TH isoforms contained
      isoform-specific regions in the regulatory ACT domain and showed differential
      expression patterns in different tissues. In addition, the dopamine receptor
      genes had a receptor subtype-specific distribution: the Dop1, Dop2, and DopEcR
      genes were broadly expressed in various tissues at differential expression
      levels, and the Dop3 gene was restrictedly expressed in neuronal tissues and the
      testicles. Our findings provide a fundamental basis for understanding the
      dopaminergic regulation of diverse physiological processes in the cricket. 

PMID- 23539477
TI  - The unbearable futility of deriving the left atrial size from a single-linear
      dimension.

PMID- 23539478
TI  - Surgical removal of subfoveal choroidal neovascularization in pathologic myopia:
      a 12-year follow-up study.
AB  - The purpose of this study was to review the 12-year visual outcomes of patients
      who underwent surgical removal for subfoveal choroidal neovascularization (CNV)
      attributable to pathologic myopia. This retrospective study included 14 patients,
      with a mean age of 45.8 years, high myopia (>6 D) and classic subfoveal CNV. They
      were treated with pars plana vitrectomy and surgical removal of CNV. All patients
      were followed up every 3 months for 2 years, with visual acuity (VA), fundus
      examination, and fluorescein angiography and then every year for 5 years. Ten
      patients underwent a final visit with VA and fundus examination after a minimum
      12-year follow-up. The main outcome measurement was VA and the secondary outcome
      measurement was the lesion size. After 12 years of follow-up, the mean VA did not
      significantly change over time, with a mean gain of 0.22 logMAR at 1 year, and
      0.18, 0.12 and 0.05 at 2, 5 and 12 years, respectively. The anatomical evolution
      was characterized by a significant enlargement of the lesion size at 5 years.
      This study showed that final VA after surgical treatment with 12 years of follow
      up was poor, due to the significant CNV scar enlargement over time. These results
      should prompt a prospective randomized study of other medical treatments,
      particularly anti-vascular endothelial growth factor therapy. 

PMID- 23539479
TI  - Influence of retinal ischemia on macular function after pars plana vitrectomy for
      macular edema with branch retinal vein occlusion.
AB  - The influence of retinal ischemia on changes of visual acuity, macular
      sensitivity, macular thickness, and macular volume is unclear after pars plana
      vitrectomy (PPV) for macular edema with branch retinal vein occlusion (BRVO).
      Twenty-three patients (23 eyes) with BRVO and macular edema underwent PPV.
      Retinal ischemia was evaluated from capillary non-perfusion on fluorescein
      angiography, and patients were classified as ischemic or nonischemic.
      Microperimetry was performed with a Micro Perimeter 1. Macular thickness and
      volume were measured by optical coherence tomography. Mean macular thickness
      within the central 4 degrees , 10 degrees , and 20 degrees  fields decreased
      significantly from before to 3 and 6 months after PPV (all P < 0.001). Likewise,
      total macular volume within the central 4 degrees , 10 degrees , and 20 degrees 
      fields decreased significantly from before to 3 and 6 months after PPV (all P <
      0.001). Best-corrected visual acuity (BCVA) improved significantly from before to
      3 and 6 months after PPV (P < 0.001). Furthermore, mean macular sensitivity
      within the central 4 degrees , 10 degrees , and 20 degrees  fields increased
      significantly from before to 3 and 6 months after PPV (P = 0.002, P = 0.001, and
      P = 0.001, respectively). There were no significant differences in the trend
      profiles of macular thickness, macular volume, and BCVA between the ischemic and
      nonischemic groups. However, there was a significant difference in the trend
      profile of macular sensitivity within the central 4 degrees , 10 degrees , and 20
      degrees  fields between the ischemic and nonischemic groups (P = 0.017, P = 0.010
      and P = 0.025, respectively). These findings suggest PPV may be more effective
      for improving macular sensitivity in ischemic than nonischemic BRVO. 

PMID- 23539480
TI  - Ocular coherence tomography findings in a case of choroideremia.

PMID- 23539481
TI  - Diagnosis and misdiagnosis of cerebrovascular disease.
AB  - OPINION STATEMENT: Stroke is the leading cause of disability and the third
      leading cause of death in the USA. Ischemic and hemorrhagic strokes must be
      distinguished since treatment is quite different. Ischemic strokes account for 80
      % of the total and recent advances in management of brain ischemia have added
      valuable options to the physicians' armamentarium. Wise selection and targeted
      treatment of patients is of paramount importance. Properly treated patients
      benefit significantly, while those erroneously diagnosed as ischemic stroke are
      exposed to potentially harmful side effects of therapy. Stroke can present in the
      form of several different clinical syndromes some of which are difficult to
      identify. Conversely, there are numerous conditions whose clinical presentation
      closely resembles stroke, also known as stroke mimics. Ancillary testing,
      especially imaging, is a crucial part of diagnostic evaluation, while clinical
      judgment, thorough knowledge of cerebrovascular anatomy and familiarity with
      characteristic stroke syndromes remain indispensable even in this era of
      technological advance.

PMID- 23539482
TI  - Combination aspirin and clopidogrel for secondary prevention of ischemic stroke.
AB  - OPINION STATEMENT: Though antiplatelet agents are the mainstay of antithrombotic
      therapy for secondary prevention of noncardioembolic cerebral ischemic events,
      the efficacy of combination aspirin and clopidogrel has yet to be clarified by
      clinical trials. Current evidence suggests that there is no role for long-term
      combination of aspirin/clopidogrel for secondary stroke prevention. Recent
      preliminary data from the CHANCE (Clopidogrel in High-risk Patients with Acute
      Non-disabling Cerebrovascular Events) trial suggests that stroke recurrence at 90
      days is reduced by a short course (21 days) of combination aspirin/clopidogrel
      initiated within 24 hours of minor stroke or TIA (Transient Ischemic Attack)
      compared with aspirin alone [1**] (Table 1). Other ongoing trials, which are also
      investigating the role of short-term combination antiplatelet therapy initiated
      immediately after minor stroke and TIA, will determine if these findings will be
      replicated.

PMID- 23539483
TI  - The importance of chromosomes from the sixth homeologic group in the restoration
      of male fertility in winter triticale with Triticum timopheevii cytoplasm.
AB  - The sterilising cytoplasm from Triticum timopheevii is presently considered to be
      the most promising as regards to the seed production of triticale hybrid
      cultivars. This study was aimed at the utilisation of Diversity Arrays Technology
      (DArT) for the preliminary identification of genomic regions with loci
      controlling male sterility/fertility in the field-grown F2 generation of the
      interline hybrid between male sterile line CMS-Salvo 15/1 and restorer line Stan
      I. The fertility of plants was examined by visual scoring as well as by the
      assessment of seed setting within bagged spikes. For DNA analyses, 92 individuals
      representing opposite phenotypes (male sterile vs. fully male fertile) were
      chosen from the whole F2 population, which consisted of 414 plants. The
      constructed genetic map consists of 759 DArT markers distributed in 24 linkage
      groups that cover a distance of 974.4 cM. Application of the interval mapping
      method and the Kruskal-Wallis test enabled the identification of six genomic
      regions engaged in the restoration of male fertility within the mapping
      population. The most effective restorer genes were found on chromosomes of the
      sixth homeologic group, i.e. on 6R (the most efficient), 6A and 6B. Additionally,
      linkage groups assigned to chromosomes 1BS, 3A and 3A/3B were important for the
      determination of male fertility.

PMID- 23539484
TI  - Vitamin D and metabolites measurement by tandem mass spectrometry.
AB  - The prevalence of vitamin D deficiency in the general population has become a
      major public health problem. Vitamin D deficiency might have significant
      consequences not only to bone health but possibly to autoimmune-, infectious and
      cardiovascular disease. This has resulted in increased clinical testing for 25
      hydroxyvitamin D (25(OH)D) in serum, as circulating 25(OH)D is regarded as the
      best indicator of adequate exposure to sunlight and dietary intake of vitamin D.
      There are reportedly over 50 vitamin D metabolites of which 25(OH)D and
      1,25(OH)2D are well known to provide clinical information. More recently, there
      is increasing interest in measuring the C3-epimer of 25(OH)D, which has shown to
      contribute significantly to the 25(OH)D concentration, particularly in infant
      populations, and in 24,25(OH)2D, a major catabolite of 25(OH)D metabolism. Liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) is an analytical tool that
      allows the specific determination of all relevant vitamin D metabolites, with the
      potential of performing multiple analyte analysis in a single experimental
      setting, creating a vitamin D profile. This article reviews recent advances in
      the quantification of vitamin D metabolites using LC-MS/MS.

PMID- 23539485
TI  - CD24 expression predicts distant metastasis in extrahepatic bile duct cancer.
AB  - AIM: To evaluate the prognostic significance of CD24 expression in patients
      undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer.
      METHODS: Eighty-four patients with EHBD cancer who underwent curative resection
      followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative
      radiotherapy was delivered to the tumor bed and regional lymph nodes up to a
      median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine
      chemotherapy for radiosensitization during radiotherapy. CD24 expression was
      assessed with immunohistochemical staining on tissue microarray.
      Clinicopathologic factors as well as CD24 expression were evaluated in
      multivariate analysis for clinical outcomes including loco-regional recurrence,
      distant metastasis-free and overall survival. RESULTS: CD24 was expressed in 36
      patients (42.9%). CD24 expression was associated with distant metastasis, but not
      with loco-regional recurrence nor with overall survival. The 5-year distant
      metastasis-free survival rates were 55.1% and 29.0% in patients with negative and
      positive expression, respectively (P = 0.0100). On multivariate analysis
      incorporating N stage, histologic differentiation and CD24 expression, N stage
      was the only significant factor predicting distant metastasis-free survival (P =
      0.0089), while CD24 expression had borderline significance (P = 0.0733). In
      subgroup analysis, CD24 expression was significantly associated with 5-year
      distant metastasis-free survival in node-positive patients (38.4% with negative
      expression vs 0% with positive expression, P = 0.0110), but not in node-negative
      patients (62.0% with negative expression vs 64.0% with positive expression, P =
      0.8599). CONCLUSION: CD24 expression was a significant predictor of distant
      metastasis for patients undergoing curative resection followed by adjuvant
      chemoradiotherapy especially for node-positive EHBD cancer.

PMID- 23539486
TI  - Epidemiology and inflammatory bowel diseases.
AB  - The role of alcohol in causing or aggravating the pathogenesis of inflammatory
      bowel disease is unclear. For finding a conclusive answer for this valuable
      question we conducted this review. Only two studies were identified that
      successfully fulfilled our inclusive criteria. Usual consumption of alcohol
      reduced the risk compared with less frequent use (odds ratio = 0.57, 95%CI: 0.37
      0.86). Light alcoholic drinking has protective effects against development of
      ulcerative colitis. But this inverse association disappeared when smoking was
      included.

PMID- 23539487
TI  - Can we still learn from single center experience after PARTNER?
AB  - With the publication of the Placement of Aortic Transcatheter Valves (PARTNER)
      trial, transcatheter aortic valve replacement (TAVR) has undoubtedly become the
      gold standard for severe aortic stenosis in patients that are not suitable
      candidate for surgical aortic valve replacement (AVR). The PARTNER trial also
      showed that TAVR is non-inferior to AVR in high-risk patients. A recent
      publication by Ben-Dor et al evaluated the outcome of high-risk patients with
      severe aortic stenosis who were referred to their institution for participation
      to the PARTNER trial. Only a minority of patients made it in the trial and the
      majority of patient ended being treated medically. Some patients were also
      treated with AVR outside the trial. The outcomes of all these patients were
      stratified by the treatment they received (AVR, TAVR or medical therapy with or
      without balloon aortic valvuloplasty). The 3 groups were different in their
      baseline characteristics. Ben-Dor et al found that patients treated medically had
      greater mortality than patients treated with TAVR or AVR. The survival of
      patients treated with TAVR was similar to those treated with AVR. Independent
      predictors of mortality were also found from their analysis. In this commentary,
      we discuss the finding of this study and compare it with the current literature.

PMID- 23539488
TI  - Sleep and Epilepsy: Strange Bedfellows No More.
AB  - Ancient philosophers and theologians believed that altered consciousness freed
      the mind to prophesy the future, equating sleep with seizures. Only recently has
      the bidirectional influences of epilepsy and sleep upon one another received more
      substantive analysis. This article reviews the complex and increasingly
      recognized interrelationships between sleep and epilepsy. NREM sleep
      differentially activates interictal epileptiform discharges during slow wave (N3)
      sleep, while ictal seizure events occur more frequently during light NREM stages
      N1 and N2. The most commonly encountered types of sleep-related epilepsies (those
      with preferential occurrence during sleep or following arousal) include frontal
      and temporal lobe partial epilepsies in adults, and benign epilepsy of childhood
      with centrotemporal spikes (benign rolandic epilepsy) and juvenile myoclonic
      epilepsy in children and adolescents. Comorbid sleep disorders are frequent in
      patients with epilepsy, particularly obstructive sleep apnea in refractory
      epilepsy patients which may aggravate seizure burden, while treatment with nasal
      continuous positive airway pressure often improves seizure frequency.
      Distinguishing nocturnal events such as NREM parasomnias (confusional arousals,
      sleep walking, and night terrors), REM parasomnias including REM sleep behavior
      disorder, and nocturnal seizures if frequently difficult and benefits from
      careful history taking and video-EEG-polysomnography in selected cases.
      Differentiating nocturnal seizures from primary sleep disorders is essential for
      determining appropriate therapy, and recognizing co-existent sleep disorders in
      patients with epilepsy may improve their seizure burden and quality of life.

PMID- 23539490
TI  - Total synthesis of (-)-dihydroprotolichesterenic acid via diastereoselective
      conjugate addition to chiral fumarates.
AB  - A diastereoselective conjugate addition of a variety of monoorganocuprates,
      Li[RCuI], to chiral fumarates to provide funtionalized succinates has been
      developed. The utility of this reaction is demonstrated in a concise total
      synthesis of (-)-dihydroprotolichesterenic acid that required only four steps and
      proceeded in an overall 31% yield.

PMID- 23539491
TI  - An Improved Synthesis of BrettPhos and RockPhos-Type Biarylphosphine Ligands.
AB  - Improved processes for the preparation of biphenyl-based phosphine ligands t
      BuBrettPhos, RockPhos, and BrettPhos are presented. The new methods, featuring
      the use of Grignard reagents and catalytic amounts of copper, are superior to the
      previous methods, which require the use of t-butyllithium and stoichiometric
      amounts of copper. Specifically, the use of less dangerous reagents provides a
      safer process, while the use of catalytic amounts of copper allows for the
      isolation of pure products in high yield. These improvements are particularly
      significant for the large scale preparation of these ligands.

PMID- 23539492
TI  - Use of propofol as an anesthetic and its efficacy on some hematological values of
      ornamental fish Carassius auratus.
AB  - The aim of this study was to determine the level of anesthesia attained in
      Carassius auratus using a propofol bath administration and using values of
      haematological profile of blood and examinations, to assess the effects of the
      fish exposure to that anaesthetic. Acute toxicity values of propofol for gold
      fish were found 96 h LC50 6.353 mg/L, 96 h LC1 2.966 mg/L and 96 h LC99 13.609
      mg/L. Time to induce anesthesia in propofol experiment was significantly higher
      than Clove oil (p < 0.05), but there was no significant difference in recovery
      time between the experiments. No significant decrease was found in Total RBC,
      WBC, HCT, MCH, MCV and leukogram indices (p > 0.05). MCHC (%) level of propofol
      experiment (13.93 +/- 1.36) showed significant (p < 0.05) decrease than Clove oil
      anesthesia (94.95 +/- 24.50) and control (62.46 +/- 21.90). Hb(g/dl) content
      (5.20 +/- 0.73) showed decrease in propofol exposure compared with control (15.41
      +/- 4.76) and clove oil experiment (25.39 +/- 5.73) (p < 0.05). 

PMID- 23539493
TI  - Tracking the development of the petaloid fertile stamen in Canna indica: insights
      into the origin of androecial petaloidy in the Zingiberales.
AB  - Flowers of the order Zingiberales demonstrate a remarkable trend of reduction in
      the number of fertile stamens; from five or six fertile, filamentous stamens
      bearing two thecae each in Musaceae and Strelitziaceae to just a single petaloid
      stamen bearing a single theca in Cannaceae and Marantaceae. As one progresses
      from ancestral to derived floral forms, 5-6 fertile stamens are replaced by 4-5
      petaloid staminodes. In Cannaceae and Costaceae, all members of the androecial
      whorls exhibit petaloidy, including the fertile stamen. In Costaceae, a single
      fertile stamen develops two thecae embedded on a broad petaloid appendage, while
      in Cannaceae the single fertile stamen is further reduced to a single theca with
      a prominent, expanded petaloid appendage. Whether petaloidy of the fertile stamen
      is a synapomorphy of the entire ginger clade (including Cannaceae, Costaceae,
      Zingiberaceae and Marantaceae), or the result of independent convergent evolution
      in Cannaceae, Costaceae, and some Zingiberaceae, is unclear. We combine a
      developmental series of the formation of the petaloid fertile stamen in Canna
      indica with data on the expression of B- and C-class floral organ identity genes
      to elucidate the organogenetic identity of the petaloid stamen and staminodes.
      Our data indicate that the single fertile theca in C. indica and its petaloid
      appendage are derived from one-half of the primordium of a single stamen, with no
      contribution from the remaining part of the stamen (i.e. the second theca
      primordium) which aborts early in development. The petaloid appendage expands
      later, and develops from the position of the filament/connective of the
      developing theca. Floral identity gene expression shows that petal identity genes
      (i.e. B-class genes) are expressed in all floral organs studied while C-class
      gene AG-1 is expressed in an increasing gradient from sepals to gynoecium, and AG
      2 is expressed in all floral organs except the petals. The canonical model for
      molecular specification of floral organ identity is not sufficient to explain
      petaloidy in the androecial whorl in Canna sp. Further studies understanding the
      regulation of gene networks are required.

PMID- 23539494
TI  - Using surface-assisted laser desorption/ionization mass spectrometry to detect ss
      and ds-oligodeoxynucleotides.
AB  - We applied surface-assisted laser desorption/ionization mass spectrometry (SALDI
      MS) with HgTe nanostructures as the matrix for the detection of single- and
      double-stranded oligodeoxynucleotides (ss-ODNs and ds-ODNs). The concentrations
      of surfactant and additives (metal ions, an amine) and the pH and ionic strength
      of the sample matrix played significantly different roles in the detection of ss-
      and ds-ODNs with various sequences. In the presence of Brij 76 (1.5 %), Hg(2+)
      (7.5 MUM), and cadaverine (10 MUM) at pH 5.0, this SALDI-MS approach allowed the
      simultaneous detection of T15, T20, T33, and T40, with limits of detection at the
      femtomole-to-picomole level and sample-to-sample intensity variation <23 %. In
      the presence of Ag(+) (1 MUM) and cadaverine (10 MUM) at pH 7.0, this technique
      allowed the detection of randomly sequenced ss- and ds-ODNs at concentrations
      down to the femtomole level. To the best of our knowledge, this paper is the
      first to report the detection of ss-ODNs (up to 50-mer) and ds-ODNs (up to 30
      base pairs) through the combination of SALDI-MS with HgTe nanostructures as
      matrices. We demonstrated the practicality of this approach through analysis of a
      single nucleotide polymorphism that determines the fate of the valine residue in
      the beta-globin of sickle cell megaloblasts.

PMID- 23539495
TI  - Assessing clinical reasoning using a script concordance test with
      electrocardiogram in an emergency medicine clerkship rotation.
AB  - OBJECTIVES: Script concordance tests (SCTs) can be used to assess clinical
      reasoning, especially in situations of uncertainty, by comparing the responses of
      examinees with those of emergency physicians. The examinee's answers are scored
      based on the level of agreement with responses provided by a panel of experts.
      Emergency physicians are frequently uncertain in the interpretation of ECGs.
      Thus, the aim of this study was to validate an SCT combined with an ECG. METHODS:
      An SCT-ECG was developed. The test was administered to medical students,
      residents and emergency physicians. Scoring was based on data from a panel of 12
      emergency physicians. The statistical analyses assessed the internal reliability
      of the SCT (Cronbach's alpha) and its ability to discriminate between the
      different groups (ANOVA followed by Tukey's post hoc test). RESULTS: The SCT-ECG
      was administered to 21 medical students, 19 residents and 12 emergency
      physicians. The internal reliability was satisfactory (Cronbach's alpha=0.80).
      Statistically significant differences were found between the groups
      (F(0.271)=21.07; p<0.0001). Moreover, significant differences (post hoc test)
      were detected between students and residents (p<0.001), students and experts
      (p<0.001), and residents and experts (p=0.017). CONCLUSIONS: This SCT-ECG is a
      valid tool to assess clinical reasoning in a context of uncertainty due to its
      high internal reliability and its ability to discriminate between different
      levels of expertise.

PMID- 23539489
TI  - Childhood determinants of adult psychiatric disorder.
AB  - The aim of this project was to assess the current evidence from longitudinal
      studies for childhood determinants of adult mental illness. Because of the
      variable and often prolonged period between factors in childhood and the
      identification of mental illness in adults, prospective studies, particularly
      birth cohorts, offer the best chance of demonstrating associations in
      individuals. A review was undertaken in 2006 of the published literature from
      longitudinal studies, together with some large-scale retrospective studies and
      relevant reviews which provided supplementary evidence. The main focus was upon
      potentially ameliorable characteristics, experiences or situations of childhood;
      however, other factors, not determinants but pre-cursors, associated with later
      mental illness could not be left out. Seven major electronic data-bases of
      published research were interrogated with a range of key-words and the results
      supplemented from personal searches, enquiries and reference trails. In excess of
      1,500 abstracts were read to select 250 papers for full review. The material was
      assessed in relation to ten factors: Psychological disturbance; Genetic
      Influences; Neurological Deviance; Neuroticism; Behaviour; School Performance;
      Adversity; Child Abuse or Neglect; Parenting and parent-child relationships;
      Disrupted and Disfunctional Families. In 2011 the search was repeated for the
      period 2006 to mid-2011, using the same search terms and supplemented in the same
      manner. Over 1,800 abstracts emerged and almost 200 papers selected for more
      detailed review. These were then integrated into the original text with
      modifications where necessary. The whole text was then revised and edited in
      January / February 2012. There is continuing evidence for the association with
      later mental ill-health for each of these ten factors, but with different degrees
      of conviction. The evidence for each is discussed in detail and weighed both
      separately and in relation to others. These are then summarised, and the research
      implications are considered. Finally, the implications for prevention are
      discussed together with the practical potential for preventive and health
      promoting programmes.

PMID- 23539496
TI  - Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: How
      can patients be better selected?
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) comprises organizing
      thrombotic obstructions in the pulmonary arteries by nonresolving thromboemboli,
      formation of fibrosis and remodeling of pulmonary blood vessels. Surgical
      pulmonary endarterectomy (PEA) is the therapy of choice for patients with
      surgically accessible CTEPH, which leads to a profound improvement in
      hemodynamics, functional class and survival. Selecting the candidates that will
      benefit from surgery is still a challenging task. Criteria for surgical
      suitability have been described but the decision-making for or against surgical
      intervention remains still subjective. The optimal characterization of the
      reciprocal contribution of large vessel and small vessel disease in the elevation
      of pulmonary vascular resistance is crucial for the indication and outcome of
      PEA. Recently, Toshner et al intended to validate the partition resistance into
      small and large vessels compartments (upstream resistance: Rup) by the occlusion
      technique in the preoperative assessment of PEA. We discuss the advantages and
      disadvantages of Rup and compare it with other hemodynamic predictor to evaluate
      operative risk in CTEPH patients.

PMID- 23539497
TI  - Effect of thienorphine on intestinal transit and isolated guinea-pig ileum
      contraction.
AB  - AIM: To evaluate the effect of thienorphine on small intestinal transit in vivo
      and on guinea-pig ileum (GPI) contraction in vitro. METHODS: The effects of
      thienorphine on intestinal transit were examined in mice and in isolated GPI.
      Buprenorphine and morphine served as controls. The distance traveled by the head
      of the charchol and the total length of the intestine were measured in vivo.
      Gastrointestinal transit was expressed as a percentage of the distance traveled
      by the head of the marker relative to the total length of the small intestine.
      The isolated GPI preparations were connected to an isotonic force transducer and
      equilibrated for at least 1 h before exposure to drugs. Acetylcholine was used
      for muscle stimulation. RESULTS: Thienorphine (0.005-1.0 mg/kg, ig) or
      buprenorphine (0.005-1.0 mg/kg, sc) dose-dependently significantly inhibited gut
      transit compared with saline. Thienorphine inhibited gut transit less than
      buprenorphine. The maximum inhibition by thienorphine on the intestinal transit
      was 50%-60%, whereas the maximum inhibition by morphine on gut transit was about
      100%. Thienorphine also exhibited less inhibition on acetylcholine-induced
      contraction of GPI, with a maximum inhibition of 65%, compared with 93%
      inhibition by buprenorphine and 100% inhibition by morphine. Thienorphine induced
      a concentration-dependent decrease in the basal tonus of spontaneous movement of
      the GPI, the effect of which was weaker than that with buprenorphine. The
      duration of the effect of thienorphine on the GPI was longer than that with
      buprenorphine. CONCLUSION: Thienorphine had less influence, but a longer duration
      of action on GPI contraction and moderately inhibited intestinal transit.

PMID- 23539498
TI  - PEComa of the colon resistant to sirolimus but responsive to
      doxorubicin/ifosfamide.
AB  - A 23-year-old male presented with a three-week-history of crampy abdominal pain
      and melaena. Colonoscopy revealed a friable mass filling the entire lumen of the
      cecum; histologically, it was classified as perivascular epithelioid cell tumor
      (PEComa). An magnetic resonance imaging scan showed, in addition to the primary
      tumor, two large mesenteric lymph node metastases and four metastatic lesions in
      the liver. The patient underwent right hemicolectomy and left hemihepatectomy
      combined with wedge resections of metastases in the right lobe of the liver, the
      resection status was R0. Subsequently, the patient was treated with sirolimus.
      After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two
      new liver metastases and a local pelvic recurrence. The visible tumor formations
      were again excised surgically, this time the resection status was R2 with regard
      to the pelvic recurrence. The patient was treated with 12 cycles of doxorubicin
      and ifosfamide under which the disease was stable for 9 mo. The clinical course
      was then determined by rapid tumor growth in the pelvic cavity. Second line
      chemotherapy with gemcitabine and docetaxel was ineffective, and the patient died
      23 mo after the onset of disease. This case report adds evidence that, in
      malignant PEComa, the mainstay of treatment is curative surgery. If not
      achievable, the effects of adjuvant or palliative chemotherapy are unpredictable.

PMID- 23539499
TI  - Aflatoxins, hepatocellular carcinoma and public health.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths
      worldwide, primarily affecting populations in the developing countries.
      Aflatoxin, a food contaminant produced by the fungi Aspergillus flavus and
      Aspergillus parasiticus, is a known human carcinogen that has been shown to be a
      causative agent in the pathogenesis of HCC. Aflatoxin can affect a wide range of
      food commodities including corns, oilseeds, spices, and tree nuts as well as
      milk, meat, and dried fruit. Many factors affect the growth of Aspergillus fungi
      and the level of aflatoxin contamination in food. Drought stress is one of the
      factors that increase susceptibility of plants to Aspergillus and thus aflatoxin
      contamination. A recent drought is thought to be responsible for finding of trace
      amounts of aflatoxin in some of the corn harvested in the United States. Although
      it's too soon to know whether aflatoxin will be a significant problem, since
      United States is the world's largest corn producer and exporter, this has raised
      alarm bells. Strict regulations and testing of finished foods and feeds in the
      United States should prevent a major health scare, and prevent human exposure to
      deleterious levels of aflatoxin. Unfortunately, such regulations and testing are
      not in place in many countries. The purpose of this editorial is to summarize the
      current knowledge on association of aflatoxin and HCC, encourage future research
      and draw attention to this global public health issue.

PMID- 23539500
TI  - Persistent region-dependent neuroinflammation, NMDA receptor loss and atrophy in
      an animal model of penetrating brain injury.
AB  - : Dynamic changes in neuroinflammation and glutamate NMDA receptors (NMDAR) have
      been noted in traumatic and ischemic brain injury. AIM: Here we investigate the
      time course and regional distribution of these changes and their relationship
      with atrophy in a rat model of penetrating brain injury. MATERIALS METHODS:
      Quantitative autoradiography, with the neuroinflammation marker [3H]PK11195 and
      the NMDAR antagonist [125I]iodoMK801, was performed on brains of animals
      subjected to a unilateral wireknife injury at the level of striatum and killed 3 
      60 days later. Regional atrophy was measured by morphometry. RESULTS: The injury
      produced large increases in [3H]PK11195 binding density in cortical and septal
      regions adjacent to the knife track by day 7, with modest increases in the
      striatum. [125I]iodoMK801 binding was reduced in cor tical and hippocampal
      regions showing marked neuroinflammation, which showed marked atrophy at
      subsequent time points. CONCLUSION: These results indicate that neuroinflammaton
      and loss of NMDAR precede and predict tissue atrophy in cortical and hippocampal
      regions.

PMID- 23539501
TI  - Nitric oxide and its metabolites in the critical phase of illness: rapid
      biomarkers in the making.
AB  - The potential of nitric oxide (NO) as a rapid assay biomarker, one that could
      provide a quantum leap in acute care, remains largely untapped. NO plays a
      crucial role as bronchodilator, vasodilator and inflammatory mediator. The main
      objective of this review is to demonstrate how NO is a molecule of heavy interest
      in various acute disease states along the emergency department and critical care
      spectrum: respiratory infections, central nervous system infections, asthma,
      acute kidney injury, sepsis, septic shock, and myocardial ischemia, to name just
      a few. We discuss how NO and its oxidative metabolites, nitrite and nitrate, are
      readily detectable in several body compartments and fluids, and as such they are
      associated with many of the pathophysiological processes mentioned above. With
      methods such as high performance liquid chromatography and chemiluminescence
      these entities are relatively easy and inexpensive to analyze. Emphasis is placed
      on diagnostic rapidity, as this relates directly to quality of care in acute care
      situations. Further, a rationale is provided for more bench, translational and
      clinical research in the field of NO biomarkers for such settings. Developing
      standard protocols for the aforementioned disease states, centered on
      concentrations of NO and its metabolites, can prove to revolutionize diagnostics
      and prognostication along a spectrum of clinical care. We present a strong case
      for developing these biomarkers more as point-of-care assays with potential of
      color gradient test strips for rapid screening of disease entities in acute care
      and beyond. This will be relevant to global health.

PMID- 23539502
TI  - Cellular signalling pathways mediating dilation of porcine pial arterioles to
      adenosine A2A receptor activation.
AB  - AIMS: Adenosine is a potent vasodilator contributing to cerebral blood flow
      regulation during metabolic stress. However, the distribution of adenosine
      receptor subtypes and underlying signalling mechanisms for dilation of pial
      arterioles remain unclear. The present study aimed at addressing these issues.
      METHODS AND RESULTS: Isolated porcine pial arterioles were subjected to study of
      vasomotor function, localization of adenosine receptors, and production of nitric
      oxide (NO). Concentration-dependent vasodilation to adenosine was inhibited by
      A2A receptor antagonist ZM241385 but not by A1 receptor antagonist 8-cyclopentyl
      1,3-dipropylxanthine. A2A receptors were detected in endothelium and smooth
      muscle of pial arterioles via immunohistochemistry. Adenosine significantly
      increased arteriolar production of NO, and the induced dilation was insensitive
      to KATP channel blocker glibenclamide but was attenuated by endothelial
      denudation, NO synthase inhibitor L-NAME, or guanylyl cyclase inhibitor ODQ in a
      similar manner. Both inward rectifier potassium (Kir) channel inhibitor barium
      and cAMP signalling inhibitor Rp-8-Br-cAMPS attenuated adenosine-induced
      dilation. In the presence of L-NAME or the absence of endothelium, addition of Rp
      8-Br-cAMPS but not barium further reduced adenosine-induced responses. Barium
      diminished endothelium-independent vasodilation to NO donor sodium nitroprusside.
      Comparable to the adenosine-induced response, vasodilation to A2A receptor
      agonist CGS21680 was attenuated by endothelial removal, ZM241385, L-NAME, barium,
      or Rp-8-Br-cAMPS, but not by glibenclamide. CONCLUSION: Adenosine evokes dilation
      of porcine pial arterioles via parallel activation of endothelial and smooth
      muscle A2A receptors. Stimulation of endothelial NO production activates smooth
      muscle guanylyl cyclase for vasodilation by opening Kir channels. Adenosine also
      activates smooth muscle cAMP signalling leading to vasodilation.

PMID- 23539503
TI  - Familial dilated cardiomyopathy mutations uncouple troponin I phosphorylation
      from changes in myofibrillar Ca2+ sensitivity.
AB  - AIMS: The pure form of familial dilated cardiomyopathy (DCM) is mainly caused by
      mutations in genes encoding sarcomeric proteins. Previous measurements using
      recombinant proteins suggested that DCM mutations in thin filament proteins
      decreased myofibrillar Ca(2+) sensitivity, but exceptions were reported. We re
      investigated the molecular mechanism of familial DCM using native proteins.
      METHODS AND RESULTS: We used the quantitative in vitro motility assay and native
      troponin and tropomyosin to study DCM mutations in troponin I, troponin T, and
      alpha-tropomyosin. Four mutations reduced myofilament Ca(2+) sensitivity, but one
      mutation (TPM1 E54K) did not alter Ca(2+) sensitivity and another (TPM1 D230N)
      increased Ca(2+) sensitivity. In thin filaments from normal human and mouse
      heart, protein kinase A (PKA) phosphorylation of troponin I caused a two- to
      three-fold decrease in myofibrillar Ca(2+) sensitivity. However, Ca(2+)
      sensitivity did not change with the level of troponin I phosphorylation in any of
      the DCM-mutant containing thin filaments (E40K, E54K, and D230N in alpha
      tropomyosin; R141W and DeltaK210 in cardiac troponin T; K36Q in cardiac troponin
      I; G159D in cardiac troponin C, and E361G in cardiac alpha-actin). This
      'uncoupling' was observed with native mutant protein from human and mouse heart
      and with recombinant mutant protein expressed in baculovirus/Sf9 systems.
      Uncoupling was independent of the fraction of mutated protein present above 0.55.
      CONCLUSION: We conclude that DCM-causing mutations in thin filament proteins
      abolish the relationship between myofilament Ca(2+) sensitivity and troponin I
      phosphorylation by PKA. We propose that this blunts the response to beta
      adrenergic stimulation and could be the cause of DCM in the long term.

PMID- 23539504
TI  - Bayesian Thurstonian models for ranking data using JAGS.
AB  - A Thurstonian model for ranking data assumes that observed rankings are
      consistent with those of a set of underlying continuous variables. This model is
      appealing since it renders ranking data amenable to familiar models for
      continuous response variables-namely, linear regression models. To date, however,
      the use of Thurstonian models for ranking data has been very rare in practice.
      One reason for this may be that inferences based on these models require
      specialized technical methods. These methods have been developed to address
      computational challenges involved in these models but are not easy to implement
      without considerable technical expertise and are not widely available in software
      packages. To address this limitation, we show that Bayesian Thurstonian models
      for ranking data can be very easily implemented with the JAGS software package.
      We provide JAGS model files for Thurstonian ranking models for general use,
      discuss their implementation, and illustrate their use in analyses. 

PMID- 23539506
TI  - Epidemiology and acquisition of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in a septic orthopedic ward.
AB  - Wards cohorting infected orthopaedic patients may be particularly prone to
      transmitting extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL
      E). We analyze their epidemic pattern by performing molecular typing of ESBL-E
      isolated from patients and healthcare workers (HCW) from our septic ward. Between
      March 2010 and November 2011, 186 patients were admitted. Among 565 anal swabs,
      ESBL-E were detected in 204 samples from 45 patients, suggesting prolonged
      carriage in affected patients. Among 25 cases with identical ESBL-E species and
      positive epidemiological links, only 9 were really attributable to our service.
      We also screened 41 healthcare workers (HCW) on 49 occasions during the study
      period. Six samples (13%) were positive. None of the ESBL-E detected in HCW were
      related to any of the patient isolates. Among 60 environmental samples taken at
      the peak of the epidemic none revealed ESBL-E. We conclude that HCW also were
      anal carriers of ESBL-E, however the ESBL- strains from the HCW were not the same
      strains isolated from patients in the septic ward. Moreover, the epidemiological
      attribution of ESBL by simple vicinity, timing, and species identification might
      grossly overestimate transmission within a given unit. 

PMID- 23539507
TI  - Electrochemical impedance spectroscopy versus cyclic voltammetry for the
      electroanalytical sensing of capsaicin utilising screen printed carbon nanotube
      electrodes.
AB  - Screen printed carbon nanotube electrodes (SPEs) are explored as
      electroanalytical sensing platforms for the detection of capsaicin in both
      synthetic capsaicin solutions and capsaicin extracted from chillies and chilli
      sauces utilising both cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS). It is found that the technique which is most applicable to
      the electroanalytical detection of capsaicin depends upon the analyte
      concentration: for the case of low capsaicin concentrations, CV is a more
      appropriate method as capsaicin exhibits characteristic voltammetric waves of
      peak heights relevant to the capsaicin concentration; but for the case of high
      capsaicin concentrations where the voltammetric waves merge and migrate out of
      the potential window, EIS is shown to be a more appropriate technique, owing to
      the observed linear increases in R(ct) with increasing concentration.
      Furthermore, we explore different types of screen printed carbon nanotube
      electrodes, namely single- and multi- walled carbon nanotubes, finding that they
      are technique-specific: for the case of low capsaicin concentrations, single
      walled carbon nanotube SPEs are preferable (SW-SPE); yet for the case of EIS at
      high capsaicin concentrations, multi-walled carbon nanotube SPEs (MW-SPE) are
      preferred, based upon analytical responses. The analytical performance of CV and
      EIS is applied to the sensing of capsaicin in grown chillies and chilli sauces
      and is critically compared to 'gold standard' HPLC analysis.

PMID- 23539505
TI  - Gadolinium-Based Contrast Agents for Vessel Wall Magnetic Resonance Imaging (MRI)
      of Atherosclerosis.
AB  - Cardiovascular disease due to atherosclerosis is the number one killer in the
      Western world, and threatens to become the major cause of morbidity and mortality
      worldwide. It is therefore paramount to develop non-invasive methods for the
      detection of high-risk, asymptomatic individuals before the onset of clinical
      symptoms or events. In the recent past, great strides have been made in the
      understanding of the pathological mechanisms involved in the atherosclerotic
      cascade down to the molecular details. This has allowed the development of
      contrast agents that can aid in the in vivo characterization of these processes.
      Gadolinium chelates are among the contrast media most commonly used in MR
      imaging. Originally used for MR angiography for the detection and quantification
      of vascular stenosis, more recently they have been applied to improve
      characterization of atherosclerotic plaques. In this manuscript, we will briefly
      review gadolinium-chelates (Gd) based contrast agents for non-invasive MR imaging
      of atherosclerosis. We will first describe Gd-based non-targeted FDA approved
      agents, used routinely in clinical practice for the evaluation of
      neovascularization in other diseases. Secondly, we will describe non-specific and
      specific targeted contrast agents, which have great potential for dissecting
      specific biological processes in the atherosclerotic cascade. Lastly, we will
      briefly compare Gd-based agents to others commonly used in MRI and to other
      imaging modalities.

PMID- 23539508
TI  - Elevated 4-aminobiphenyl and 2,6-dimethylaniline hemoglobin adducts and increased
      risk of bladder cancer among lifelong nonsmokers--The Shanghai Bladder Cancer
      Study.
AB  - BACKGROUND: 4-Aminobiphenyl (ABP) is an established human bladder carcinogen,
      with tobacco smoke being a major source of human exposure. Other arylamine
      compounds, including 2,6-dimethylaniline (2,6-DMA), have been implicated as
      possible human bladder carcinogens. Hemoglobin adducts of 4-ABP and 2,6-DMA are
      validated biomarkers of exposure to those compounds in humans. METHODS: The
      Shanghai Bladder Cancer Study enrolled 581 incident bladder cancer cases and 604
      population controls. Each participant was solicited for his/her history of
      tobacco use and other lifestyle factors and donation of blood and urine
      specimens. Red blood cell lysates were used to quantify both hemoglobin adducts
      of 4-ABP and 2,6-DMA. Urine samples were used to quantify total cotinine. ORs and
      95% confidence intervals (CI) for bladder cancer were estimated using
      unconditional logistic regression methods. RESULTS: Among lifelong nonsmokers,
      ORs (95% CIs) of bladder cancer for low (below median of positive values) and
      high versus undetectable levels of 2,6-DMA hemoglobin adducts were 3.87 (1.39
      10.75) and 6.90 (3.17-15.02), respectively (Ptrend < 0.001). Similarly, among
      lifelong nonsmokers, ORs (95% CIs) of bladder cancer for third and fourth versus
      first/second quartiles of 4-ABP hemoglobin adducts was 1.30 (0.76-2.22) and 2.29
      (1.23-4.24), respectively (Ptrend = 0.009). The two associations were independent
      of each other. CONCLUSION: Hemoglobin adducts of 4-ABP and 2,6-DMA were
      significantly and independently associated with increased bladder cancer risk
      among lifelong nonsmokers in Shanghai, China. IMPACT: The findings of the present
      study in China with previous data in Los Angeles, California strongly implicate
      arylamines as potential causal agents of human bladder cancer.

PMID- 23539509
TI  - Role of three-body recombination for charge reduction in MALDI process.
AB  - Ions in Matrix-Assisted Laser Desorption/Ionization (MALDI) are predominantly
      singly charged for small analyte molecules. With the estimated high number
      density and low temperature of electrons, the three-body recombination mechanism
      is attractive and should be considered as an important cause for the charge
      reduction in the plume. Theoretical calculations indicate that the rate
      coefficient of the three-body recombination is about 50 times higher than that of
      the two-body recombination if the analyte molecule has insufficient degrees of
      freedom. Experimental results show that, for small analyte molecules, the ratio
      of AH2(2+)/AH(+) is close to the theoretical 5% value from the three-body
      recombination modeling and this ratio declines with the increasing electron and
      matrix molecule number density caused by greater laser irradiance. The ratio of
      [A + 2](+)/[A + 1](+) is higher than the theoretical isotopic value, and the
      excess [A + 2](+) could exclusively result from the three-body recombination
      collisions. Further evidence demonstrates that [A + 2](+)/[A + 1](+) increases
      with electron number density, which is in correspondence with the model. All of
      these theoretical and experimental results indicate that three-body recombination
      is an essential charge reduction mechanism for small molecules in the MALDI
      plume.

PMID- 23539510
TI  - Insulin-like factor 3 promotes wound healing at the ocular surface.
AB  - Tear fluid is known to contain many different hormones with relevance for ocular
      surface homeostasis. We studied the presence and functional role of insulin-like
      factor 3 (INSL3) and its cognate receptor RXFP2 (relaxin/insulin-like family
      peptide receptor 2) at the ocular surface and in tears. Expression of human INSL3
      and RXFP2 was determined in tissues of the ocular surface and lacrimal apparatus;
      in human corneal (HCE), conjunctival (HCjE), and sebaceous (SC) epithelial cell
      lines; and in human tears by RT-PCR and ELISA. We investigated effects of human
      recombinant INSL3 (hrINSL3) on cell proliferation and cell migration and the
      influence of hrINSL3 on the expression of MMP2, -9, and -13 and TIMP1 and -2 was
      quantified by real-time PCR and ELISA in HCE, HCjE, and SC cells. We used a
      C57BL/6 mouse corneal defect model to elucidate the effect of topical application
      of hrINSL3 on corneal wound healing. INSL3 and RXFP2 transcripts and INSL3
      protein were detected in all tissues and cell lines investigated. Significantly
      higher concentrations of INSL3 were detected in tears from male vs. female
      volunteers. Stimulation of HCE, HCjE, and SC with hrINSL3 significantly increased
      cell proliferation in HCjE and SC and migration of HCjE. Treatment with hrINSL3
      for 24 hours regulated MMP2, TIMP1, and TIMP2 expression. The local application
      of hrINSL3 onto denuded corneal surface resulted in significantly accelerated
      corneal wound healing in mice. These findings suggest a novel and gender-specific
      role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis
      and determined a novel role for hrINSL3 in corneal wound healing.

PMID- 23539511
TI  - Cardiac natriuretic Peptide gene expression and plasma concentrations during the
      first 72 hours of life in piglets.
AB  - Plasma measurement of cardiac natriuretic peptides constitutes promising markers
      of congenital heart disease. However, concentrations change rapidly and
      dramatically during the first days after delivery even in healthy neonates, which
      complicates clinical interpretation. It is unknown whether these changes in
      plasma concentrations are explained by corresponding changes in the cardiac gene
      expression. We quantified the chamber-specific mRNA levels of ANP (A-type
      natriuretic peptide) and BNP (B-type natriuretic peptide) and plasma pro-ANP and
      BNP-32 concentrations in healthy piglets during the first 72 hours of life (from
      2 litters, n = 44). Chamber-specific ANP and BNP mRNA levels reflected
      hemodynamic neonate changes at birth but did not correlate with circulating
      natriuretic peptide concentrations. However, plasma pro-ANP and creatinine
      concentrations were closely correlated (P < .0001; r = 0.73). Plasma pro-ANP
      levels were highest on the day of delivery (5580 pmol/L [4320-6786] decreasing to
      2484 pmol/L [1602-2898] after 72 hours, P < .0001). During the 72 hours, gel
      chromatography suggested that the translational products in circulation and in
      atrial tissue were immature, ie, unprocessed pro-ANP. In contrast to pro-ANP, BNP
      32 plasma concentrations were low at delivery and peaked after 48 hours (12 [10.5
      20.6] vs. 88.8 [71.7-101.4] pmol/L, P < .0001). To conclude, ANP and BNP gene
      expression differs considerably between cardiac chambers in the first 72 hours of
      life in healthy piglets, resembling the transition from fetal to neonate
      circulation. However, the cardiac gene expression does not explain plasma
      concentrations.

PMID- 23539512
TI  - Preincubation of pituitary tumor cells with the epidrugs zebularine and
      trichostatin A are permissive for retinoic acid-augmented expression of the BMP-4
      and D2R genes.
AB  - Retinoic acid (RA)-induced expression of bone morphogenetic protein-4 (BMP-4)
      inhibits in vitro and in vivo cell proliferation and ACTH synthesis in
      corticotroph-derived tumor cells. Reduced expression of BMP-4 in this adenoma
      subtype is associated with epigenomic silencing, and similar silencing mechanisms
      are also associated with the RA-responsive dopamine D2 receptor (D2R) in
      somatolactotroph cells. We now show that preincubation with the epidrugs
      zebularine and trichostatin A is obligate and permissive for RA-induced
      expression of the BMP-4 and the D2R genes in pituitary tumor cells. Combined
      epidrug challenges are associated with marginal reduction in CpG island
      methylation. However, significant change to histone tail modifications toward
      those associated with expression-competent genes is apparent, whereas RA
      challenge alone or in combined incubations does not have an impact on these
      modifications. Epidrug-mediated and RA-augmented expression of endogenous BMP-4
      increased or decreased cell proliferation and colony-forming efficiency in GH3
      and AtT-20 pituitary tumor cells, respectively, recapitulating recent reports of
      challenges of these cells with exogenous ligand. The specificity of the BMP-4
      mediated effects was further supported by knock-down experiments of the BMP-4
      antagonist noggin (small interfering RNA [siRNA]). Knock-down of noggin, in the
      absence and the presence of epidrugs, induced and augmented BMP-4 expression,
      respectively. In cell proliferation assays, challenge with either epidrugs or
      siRNA led to significant increase in cell numbers at the 72-hour time point;
      however, in siRNA-treated cells coincubated with epidrugs, a significant increase
      was apparent at the 48-hour time point. These studies show the potential of
      combined drug challenges as a treatment option, where epidrug renders silenced
      genes responsive to conventional therapeutic options.

PMID- 23539513
TI  - Shedding new light on the origins of olfactory neurons.
AB  - Sensory neurons in the nose of the zebrafish are derived from both neural crest
      cells and placode cells.

PMID- 23539514
TI  - The chemistry of pristine graphene.
AB  - Graphene is a unique material with outstanding mechanical and electronic
      properties. For solution processes graphene layers have to be stabilized by means
      of molecular or supramolecular chemical derivatization, prior to their transfer
      to solid substrates. The most common chemical methodology for the preparation of
      graphene involves the formation of graphene oxide under highly oxidizing
      conditions, which even after reduction, lacks the electronic quality of pristine
      graphene. Presently, there is increasing concern in the chemical community about
      the starting material quality, and recent efforts are directed to wet chemical
      approaches toward high-quality graphene flakes which encompass the use of
      graphite as initial material. In addition, epitaxial growth of graphene on
      metallic surfaces is becoming a powerful technique for the production of pristine
      graphene with a control on its electronic properties, somehow due to the
      supramolecular interaction with the metallic surface. Current approaches for the
      preparation of modified pristine graphene are the aim of this review.

PMID- 23539515
TI  - Treating blood pressure to prevent strokes: The age factor.
AB  - The importance of systolic blood pressure (SBP), diastolic blood pressure (DBP),
      and pulse pressure (PP), on the incidence of coronary heart disease (CHD) and
      stroke are known. However, the importance of blood pressure (BP)-age shifts
      regarding the stroke incidence is not clearly known. The BP changes with the
      advancement of age from the predominance of DBP in the young to the predominance
      of SBP in the old. This change is due to the stiffening of the large arteries as
      a result of the aging process and the replacement of the elastic fibers with
      collagen fibers. This change results in the loss of compliance and the elastic
      recoil of these vessels leading to increase in pulse wave velocity, central SBP
      and widening of pulse pressure leading to an increased incidence of CHD and
      strokes. It has been demonstrated epidemiologically that the SBP rises linearly
      with age, whereas the DBP rises up to the age of 45-50 years, and then begins to
      decline after the age of 60 years leading to a progressive widening of PP.
      Several studies have shown an inverse relationship between DBP and CHD, whereas
      no such relationship has been demonstrated for stroke. However, a recent study
      showed an inverse relationship with DBP and stroke when it dropped below 71 mmHg
      in subjects 50 years of age or older. In contrast, there was a positive
      association between BP and stroke when both SBP and DBP were >= 71 mmHg. These
      findings suggest that in treating systolic hypertension in the elderly to reduce
      stroke risk, attention should be paid on the potential harm of low DBP and the
      widening of PP regarding CHD and stroke. The implications of BP shifts with age
      and the potential risks of low DBP regarding the risk of stroke will be discussed
      in this concise review.

PMID- 23539516
TI  - Biofuels from waste.

PMID- 23539517
TI  - Natural phage nanoparticle-mediated real-time immuno-PCR for ultrasensitive
      detection of protein marker.
AB  - Current immuno-PCR methods either use bare or nanostructured DNA as a reporter or
      combine phage display for antigen binding and reporting, however, they are often
      complex to carry out and lack universality. We present a novel and universal
      design of immuno-PCR termed natural phage nanoparticle-mediated real-time immuno
      PCR.

PMID- 23539518
TI  - Remarkable enhancement of upconversion fluorescence and confocal imaging of PMMA
      Opal/NaYF(4):Yb(3+), Tm(3+)/Er(3+) nanocrystals.
AB  - Novel PMMA opal photonic crystal/NaYF(4):Yb(3+), Tm(3+)/Er(3+) nanocrystal
      composites were fabricated and tremendous improvement in upconversion
      luminescence (UCL) was observed under infrared 980 nm excitation. They were also
      explored to improve brightness of cell images.

PMID- 23539519
TI  - The relationship between academic achievement and likelihood of police arrest
      among delinquents.
AB  - Drawing upon a recent study on the association between low self-control and
      differential responses from the criminal justice system, this study examined
      whether academic performance, a construct linked to self-control, was also
      associated with the probability of police arrest. The result indicated that
      academic performance did have a statistically significant inverse association
      with the likelihood of police arrest, net of low self-control and delinquency. 

PMID- 23539520
TI  - Managing risk and marginalizing identities: on the society-of-captives thesis and
      the harm of social dis-ease.
AB  - This article develops the constitutive features of the society-of-captives thesis
      as suggested by Arrigo and Milovanovic, and Arrigo, Bersot, and Sellers. The
      relevance of this thesis is briefly explored in relation to the institutional and
      community-based treatment philosophies that currently inform the mental health
      and criminal justice systems. This exploration specifies how risk (being human
      and doing humanness differently) is managed symbolically, linguistically,
      materially, and culturally. The management of this risk extends to the kept as
      well as to their keepers, regulators, and watchers (i.e., the society of
      captives). This article calls for a new clinical praxis (being/doing a critical
      mindfulness) designed to overcome the totalizing madness (the harm of social dis
      ease) that follows from managing risk fearfully and marginalizing identities
      desperately as reified recursively through society's captivity. The ethical
      underpinnings of this clinical praxis represent an emergent direction for
      undertaking correctional policy reform.

PMID- 23539522
TI  - A novel tellurophene-containing conjugated polymer with a dithiophenyl
      diketopyrrolopyrrole unit for use in organic thin film transistors.
AB  - A new tellurophene-based pi-conjugated polymer, PDTDPPTe, was synthesized.
      PDTDPPTe exhibits a smaller optical band gap (E(g)(opt) = 1.25 eV) than thiophene
      based PDTDPPT (E(g)(opt) = 1.30 eV). Thin-film transistors comprising PDTDPPTe
      displayed outstanding performance (MU(max) = 1.78 cm(2) V(-1) s(-1), I(on)/I(off)
      = 10(5-6)).

PMID- 23539521
TI  - Decision making for pancreatic resection in patients with intraductal papillary
      mucinous neoplasms.
AB  - AIM: To identify a practical approach for preoperative decision-making in
      patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
      METHODS: Between March 1999 and November 2006, the clinical characteristics,
      pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of
      54 IPMNs cases were retrieved and analyzed. The relationships between the above
      data and decision-making for pancreatic resection were analyzed using SPSS 13.0
      software. Univariate analysis of risk factors for malignant or invasive IPMNs was
      performed with regard to the following variables: carcinoembryonic antigen,
      carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images.
      Receiver operating characteristic (ROC) curve analysis for pancreatic resection
      was performed using significant factors from the univariate analysis. RESULTS:
      CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid
      component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had
      good predictive value for determining pancreatic resection (P < 0.05), but with
      limitations. Combining the above factors (CT/MRI images and CA19-9) improved the
      accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC
      analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023),
      with a sensitivity, specificity, positive predictive value and negative
      predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. CONCLUSION:
      Combining preoperative CT/MRI images and CA19-9 level may provide useful
      information for surgical decision-making in IPMNs.

PMID- 23539523
TI  - Infliximab induces remission in cryptogenic multifocal ulcerous stenosing
      enteritis: first case.
AB  - We present the case of a 29-year-old patient with a history of abdominal pain and
      vomiting. Based on wireless video capsule findings he was previously diagnosed
      with ileal Crohn's disease at a different institution, although the clinical and
      radiological picture was not typical and the response to corticosteroids was
      poor. We performed a single-balloon enteroscopy showing a short, ulcerous
      stenosis 50 cm proximal from Bauhin's valve. The endoscopic and clinical
      histopathological findings were compatible with cryptogenic multifocal ulcerous
      stenosing enteritis (CMUSE). High dose corticosteroids were again started,
      without effect. The monoclonal tumor necrosis factor-alpha (TNF-alpha) antibody
      infliximab was added to the medical therapy. After induction therapy, both
      clinical and endoscopic amelioration was obtained. Larger case studies are needed
      to confirm the efficacy of TNF-alpha inhibition in steroid refractory CMUSE.

PMID- 23539524
TI  - PROFILE CONTROL CHARTS BASED ON NONPARAMETRIC L-1 REGRESSION METHODS.
AB  - Classical statistical process control often relies on univariate characteristics.
      In many contemporary applications, however, the quality of products must be
      characterized by some functional relation between a response variable and its
      explanatory variables. Monitoring such functional profiles has been a rapidly
      growing field due to increasing demands. This paper develops a novel
      nonparametric L-1 location-scale model to screen the shapes of profiles. The
      model is built on three basic elements: location shifts, local shape distortions,
      and overall shape deviations, which are quantified by three individual metrics.
      The proposed approach is applied to the previously analyzed vertical density
      profile data, leading to some interesting insights.

PMID- 23539525
TI  - Role of SCH79797 in maintaining vascular integrity in rat model of subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Plasma thrombin concentration is increased after
      subarachnoid hemorrhage (SAH). However, the role of thrombin receptor (protease
      activated receptor-1 [PAR-1]) in endothelial barrier disruption has not been
      studied. The aims of this study were to investigate the role of PAR-1 in
      orchestrating vascular permeability and to assess the potential therapeutics of a
      PAR-1 antagonist, SCH79797, through maintaining vascular integrity. METHODS:
      SCH79797 was injected intraperitoneally into male Sprauge-Dawley rats undergoing
      SAH by endovascular perforation. Assessment was conducted at 24 hours after SAH
      for brain water content, Evans blue content, and neurobehavioral testing. To
      explore the role of PAR-1 activation and the specific mechanism of SCH79797's
      effect after SAH, Western blot, immunoprecipitation, and immunofluorescence of
      hippocampus tissue were performed. A p21-activated kinase-1 (PAK1) inhibitor, IPA
      3, was used to explore the underlying protective mechanism of SCH79797. RESULTS:
      At 24 hours after SAH, animals treated with SCH79797 demonstrated a reduction in
      brain water content, Evans blue content, and neurobehavioral deficits. SCH79797
      also attenuated PAR-1 expression and maintained the level of vascular endothelial
      cadherin, an important component of adherens junctions. Downstream to PAR-1, c
      Src-dependent activation of p21-activated kinase-1 led to an increased
      serine/threonine phosphorylation of vascular endothelial-cadherin;
      immunoprecipitation results revealed an enhanced binding of phosphorylated
      vascular endothelial-cadherin with endocytosis orchestrator beta-arrestin-2.
      These pathological states were suppressed after SCH79797 treatment. CONCLUSIONS:
      PAR-1 activation after SAH increases microvascular permeability, at least, partly
      through a PAR-1-c-Src-p21-activated kinase-1-vascular endothelial-cadherin
      phosphorylation pathway. Through suppressing PAR-1 activity, SCH79797 plays a
      protective role in maintaining microvascular integrity after SAH.

PMID- 23539526
TI  - The iScore predicts functional outcome in Korean patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Several stroke risk scores for prediction of functional
      outcome have been developed, but rarely validated in Asian populations. We
      assessed the validity of the iScore, recently developed from Canadian stroke
      population, in an Asian stroke population from Korea. METHODS: We applied the
      iScore to 4061 eligible participants with acute ischemic stroke in the nationwide
      multicenter stroke registry in Korea. The main outcome was poor functional
      outcome defined as having a modified Rankin Scale 3 to 6 at 3 months after stroke
      onset. The secondary outcome was death at 3 months. C-statistics were calculated
      to assess performance of the iScore. RESULTS: Poor functional outcome was found
      in 1496 patients (36.8%), whereas death at 3 months occurred in 294 patients
      (7.2%). C-statistics were 0.819 (95% confidence interval, 0.805-0.833) for poor
      functional outcome and 0.861 (95% confidence interval, 0.840-0.883) for death.
      Overall, there was a high correlation between observed and expected outcomes for
      poor functional outcome (Pearson correlation coefficient, r=0.990) and for death
      (r=0.969) according to risk score. CONCLUSIONS: The iScore reliably predicts poor
      functional outcome or death at 3 months after stroke in Korean patients.

PMID- 23539527
TI  - Early perfusion computerized tomography imaging as a radiographic surrogate for
      delayed cerebral ischemia and functional outcome after subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: To date, there is no immediate radiographic surrogate to
      quantify primary cerebral injury to identify patients at risk for delayed
      cerebral ischemia and poor clinical outcome after aneurysmal subarachnoid
      hemorrhage. Therefore, we investigated the relation of early cerebral perfusion
      computerized tomography and clot volume with radiological events of delayed
      cerebral ischemia and clinical outcome in patients with aneurysmal subarachnoid
      hemorrhage. METHODS: Data from 2 cohorts of patients (51 in main, 28 patients in
      control cohort) with aneurysmal subarachnoid hemorrhage, receiving computerized
      tomography and perfusion-computerized tomography scanning <12 hours after ictus,
      were included. A risk group model for functional outcome was developed on the
      basis of early mean transit time (MTT) and volumetric blood clot measurements.
      The relation of the risk group model with subsequent MTT, angiographic vasospasm,
      new cerebral infarction, and functional outcome was analyzed. Actual and
      predicted functional outcomes based on the risk group model were compared in the
      control cohort. RESULTS: The risk group model correlated significantly with
      subsequent MTT measurements, cerebral infarction, and functional outcome. Odds
      for poor outcome were significantly higher in case of concomitant increase of
      early MTT and clot volumes, as opposed to exclusive early MTT or clot volume
      increase. For patients in the high- or low-risk groups, neurological outcome in
      the control cohort correlated significantly with predicted outcomes. CONCLUSIONS:
      Assessment of early cerebral perfusion and intracranial blood clot may serve as a
      radiographic surrogate for delayed cerebral ischemia and functional outcome in
      patients with aneurysmal subarachnoid hemorrhage using risk group modeling.

PMID- 23539528
TI  - Letter to the editor by Gregson et al regarding article, "minimally invasive
      surgery for spontaneous supratentorial intracerebral hemorrhage: a meta-analysis
      of randomized controlled trials".

PMID- 23539529
TI  - Dietary fiber intake and risk of first stroke: a systematic review and meta
      analysis.
AB  - BACKGROUND AND PURPOSE: Fiber intake is associated with reduced stroke risk in
      prospective studies, but no meta-analysis has been published to date. METHODS:
      Multiple electronic databases were searched for healthy participant studies
      reporting fiber intake and incidence of first hemorrhagic or ischemic stroke,
      published between January 1990 and May 2012. RESULTS: Eight cohort studies from
      the United States, northern Europe, Australia, and Japan met inclusion criteria.
      Total dietary fiber intake was inversely associated with risk of hemorrhagic plus
      ischemic stroke, with some evidence of heterogeneity between studies (I(2);
      relative risk per 7 g/day, 0.93; 95% confidence interval, 0.88-0.98; I(2)=59%).
      Soluble fiber intake, per 4 g/day, was not associated with stroke risk reduction
      with evidence of low heterogeneity between studies, relative risk 0.94 (95%
      confidence interval, 0.88-1.01; I(2)=21%). There were few studies reporting
      stroke risk in relation to insoluble fiber or fiber from cereals, fruit, or
      vegetables. CONCLUSIONS: Greater dietary fiber intake is significantly associated
      with lower risk of first stroke. Overall, findings support dietary
      recommendations to increase intake of total dietary fiber. However, a paucity of
      data on fiber from different foods precludes conclusions regarding the
      association between fiber type and stroke. There is a need for future studies to
      focus on fiber type and to examine risk for ischemic and hemorrhagic strokes
      separately.

PMID- 23539530
TI  - Mesenchymal stem cell transplantation attenuates brain injury after neonatal
      stroke.
AB  - BACKGROUND AND PURPOSE: Brain injury caused by stroke is a frequent cause of
      perinatal morbidity and mortality with limited therapeutic options. Mesenchymal
      stem cells (MSC) have been shown to improve outcome after neonatal hypoxic
      ischemic brain injury mainly by secretion of growth factors stimulating repair
      processes. We investigated whether MSC treatment improves recovery after neonatal
      stroke and whether MSC overexpressing brain-derived neurotrophic factor (MSC
      BDNF) further enhances recovery. METHODS: We performed 1.5-hour transient middle
      cerebral artery occlusion in 10-day-old rats. Three days after reperfusion, pups
      with evidence of injury by diffusion-weighted MRI were treated intranasally with
      MSC, MSC-BDNF, or vehicle. To determine the effect of MSC treatment, brain
      damage, sensorimotor function, and cerebral cell proliferation were analyzed.
      RESULTS: Intranasal delivery of MSC- and MSC-BDNF significantly reduced infarct
      size and gray matter loss in comparison with vehicle-treated rats without any
      significant difference between MSC- and MSC-BDNF-treatment. Treatment with MSC
      BDNF significantly reduced white matter loss with no significant difference
      between MSC- and MSC-BDNF-treatment. Motor deficits were also improved by MSC
      treatment when compared with vehicle-treated rats. MSC-BDNF-treatment resulted in
      an additional significant improvement of motor deficits 14 days after middle
      cerebral artery occlusion, but there was no significant difference between MSC or
      MSC-BDNF 28 days after middle cerebral artery occlusion. Furthermore, treatment
      with either MSC or MSC-BDNF induced long-lasting cell proliferation in the
      ischemic hemisphere. CONCLUSIONS: Intranasal administration of MSC after neonatal
      stroke is a promising therapy for treatment of neonatal stroke. In this
      experimental paradigm, MSC- and BNDF-hypersecreting MSC are equally effective in
      reducing ischemic brain damage.

PMID- 23539531
TI  - Microbial manipulation as primary therapy for Crohn's disease.
AB  - While antimicrobials are clinically effective in preventing post-operative
      recurrence, the role for antibiotics in primary therapy for Crohn's disease (CD)
      remains unclear. The recent multicenter phase 2 trial by Prantera et al received
      wide attention because it demonstrated an increase in the week 12 remission rate
      in patients with moderately active CD treated with rifaximin and renewed interest
      in microbial manipulation as primary therapy for CD. In this commentary, we
      discuss aspects of durability, immune cell polarization, and safety of microbial
      manipulation as primary therapy for CD.

PMID- 23539532
TI  - Bean common bacterial blight: pathogen epiphytic life and effect of irrigation
      practices.
AB  - In recent years, bean common bacterial blight (CBB) caused by Xanthomonas
      axonopodis pv. phaseoli (Xap) has caused serious yield losses in several
      countries. CBB is considered mainly a foliar disease in which symptoms initially
      appear as small water-soaked spots that then enlarge and become necrotic and
      usually bordered by a chlorotic zone. Xap epiphytic population community has a
      critical role in the development of the disease and subsequent epidemics. The
      epiphytic population of Xap in the field has two major parts; solitary cells
      (potentially planktonic) and biofilms which are sources for providing and
      refreshing the solitary cell components. Irrigation type has a significant effect
      on epiphytic population of Xap. The mean epiphytic population size in the field
      with an overhead sprinkler irrigation system is significantly higher than
      populations under furrow irrigation. A significant positive correlation between
      the epiphytic population size of Xap and disease severity has been reported in
      both the overhead irrigated (r=0.64) and the furrow irrigated (r= 0.44) fields. 

PMID- 23539533
TI  - Another aspect-oriented approach to diagnosis of cardiac amyloidosis.

PMID- 23539534
TI  - Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive
      pulmonary disease: a randomised clinical trial.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a common lung disease
      leading to progressive decline in lung function. Inhibition of release of
      inflammatory mediators by p38 inhibitors may be a useful treatment for chronic
      inflammation of the airways thought to underlie the pathogenesis of the disease.
      OBJECTIVES: To evaluate the efficacy and safety of PH-797804, a potent and
      selective p38 inhibitor, in adults with moderate to severe COPD (Global
      Initiative for Chronic Obstructive Lung Disease stage II/III). METHODS: This was
      a randomised, adaptive design, double-blind, placebo-controlled, parallel-group,
      multicentre trial. Patients were initially randomised to placebo, 0.5, 3, 6 or 10
      mg PH-797804 once daily and treated for 6 weeks following a 2-week run-in.
      MEASUREMENTS AND MAIN RESULTS: The primary endpoint was change from baseline in
      trough forced expiratory volume in 1 s (FEV1) compared with placebo after 6 weeks
      of treatment. Secondary endpoints included other spirometric parameters,
      transition dyspnoea index, rescue mediation use, high sensitivity C-reactive
      protein and symptoms. A total of 230 patients were assigned to treatment; placebo
      (n=45), 0.5 mg (n=20), 3 mg (n=47), 6 mg (n=70) and 10 mg (n=48). PH-797804
      showed a statistically significant improvement in trough FEV1 at week 6 compared
      with placebo of 0.086 litre (95% Bayesian CI 0.008 to 0.164) and 0.093 litre (95%
      CI 0.018 to 0.166) at 3 and 6 mg PH-797804, respectively. PH-797804 3 mg and 6 mg
      showed an improvement in the baseline dyspnoea index/transition dyspnoea index
      total focal score at week 6. PH-797804 was well tolerated at all doses studied.
      CONCLUSIONS: PH-797804 demonstrated improvements over placebo in lung function
      parameters and dyspnoea in patients with moderate to severe COPD. TRIALREGNO:
      NCT00559910.

PMID- 23539535
TI  - The endogenous opioids related with antinociceptive effects induced by electrical
      stimulation into the amygdala.
AB  - Pain relief is necessary and essential for dental treatments. Recently, the
      relationships of pain and emotion were studied, and electrical stimulation
      applied to the amygdala depressed the nociceptive response in the anterior
      cingulate cortex (ACC). Thus, the antinociceptive effects of the amygdala are
      elucidated, but its mechanism is not yet clarified. The present study was
      performed to investigate whether endogenous opioid system is related to the
      depression, and the quantitative changes of endogenous opioids induced by
      electrical stimulation to the amygdala. We investigated immunohistologically c
      Fos expression to confirm the activated neurons, as well as the distribution and
      the amount of endogenous opioids (beta-endorphin, enkephalin and dynorphin A) in
      the brain using male Wistar rats, when electrical stimulation was applied to the
      central nucleus of the amygdala (CeA) or noxious stimulation was delivered to the
      peripheral tissue. c-Fos expression in the ipsilateral ACC was increased by
      electrical stimulation to the CeA. However, only a small amount of endogenous
      opioids was observed in the ACC when noxious stimulation or electrical
      stimulation was applied. In contrast, the amount of dynorphin A in the
      periaqueductal gray (PAG) was increased by electrical stimulation to the CeA, and
      the amount of beta-endorphin in the PAG was increased by noxious stimulation to
      the peripheral tissue. The results suggest that dynorphin A in the PAG induced by
      electrical stimulation to the CeA activate the descending antinociceptive system,
      and suggest that the nociceptive response in the ACC is depressed indirectly.

PMID- 23539537
TI  - Insights into pathological mechanisms of missense mutations in C-terminal domains
      of von Willebrand factor causing qualitative or quantitative von Willebrand
      disease.
AB  - The carboxyl-terminal domains of von Willebrand factor, D4-CK, are cysteine-rich
      implying that they are structurally important. In this study we characterized the
      impact of five cysteine missense mutations residing in D4-CK domains on the
      conformation and biosynthesis of von Willebrand factor. These variants were
      identified as heterozygous in type 1 (p.Cys2619Tyr and p.Cys2676Phe), type 2A
      (p.Cys2085Tyr and p.Cys2327Trp) and as compound heterozygous in type 3
      (p.Cys2283Arg) von Willebrand disease. Transient expression of human cell lines
      with wild-type or mutant von Willebrand factor constructs was performed. The
      mutated and wild-type recombinant von Willebrand factors were quantitatively and
      qualitatively assessed and compared. Storage of von Willebrand factor in pseudo
      Weibel-Palade bodies was studied with confocal microscopy. The structural impact
      of the mutations was analyzed by homology modeling. Homozygous expressions showed
      that these mutations caused defects in multimerization, elongation of pseudo
      Weibel-Palade bodies and secretion of von Willebrand factor. Co-expressions of
      wild-type von Willebrand factor and p.Cys2085Tyr, p.Cys2327Trp and p.Cys2283Arg
      demonstrated defective multimer assembly, suggesting a new pathological mechanism
      for dominant type 2A von Willebrand disease due to mutations in D4 and B domains.
      Structural analysis revealed that mutations p.Cys2283Arg, p.Cys2619Tyr and
      p.Cys2676Phe disrupted intra-domain disulfide bonds, whereas p.Cys2327Trp might
      affect an inter-domain disulfide bond. The p.Cys2327Trp variant is distinguished
      from the other mutants by an electrophoretic mobility shift of the multimer
      bands. The results highlight the importance of cysteine residues within the
      carboxyl-terminal of von Willebrand factor on structural conformation of the
      protein and consequently multimerization, storage, and secretion of von
      Willebrand factor. 

PMID- 23539538
TI  - Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on
      neoplastic mast cells carrying KIT D816V.
AB  - Patients with advanced systemic mastocytosis, including mast cell leukemia, have
      a poor prognosis. In these patients, neoplastic mast cells usually harbor the KIT
      mutant D816V that confers resistance against tyrosine kinase inhibitors. We
      examined the effects of the multi-kinase blocker ponatinib on neoplastic mast
      cells and investigated whether ponatinib acts synergistically with other
      antineoplastic drugs. Ponatinib was found to inhibit the kinase activity of KIT
      G560V and KIT D816V in the human mast cell leukemia cell line HMC-1. In addition,
      ponatinib was found to block Lyn- and STAT5 activity in neoplastic mast cells.
      Ponatinib induced growth inhibition and apoptosis in HMC-1.1 cells (KIT G560V(+))
      and HMC-1.2 cells (KIT G560V(+)/KIT D816V(+)) as well as in primary neoplastic
      mast cells. The effects of ponatinib were dose-dependent, but higher IC50-values
      were obtained in HMC-1 cells harboring KIT D816V than in those lacking KIT D816V.
      In drug combination experiments, ponatinib was found to synergize with
      midostaurin in producing growth inhibition and apoptosis in HMC-1 cells and
      primary neoplastic mast cells. The ponatinib+midostaurin combination induced
      substantial inhibition of KIT-, Lyn-, and STAT5 activity, but did not suppress
      Btk. We then applied a Btk short interfering RNA and found that Btk knockdown
      sensitizes HMC-1 cells against ponatinib. Finally, we were able to show that
      ponatinib synergizes with the Btk-targeting drug dasatinib to produce growth
      inhibition in HMC-1 cells. In conclusion, ponatinib exerts major growth
      inhibitory effects on neoplastic mast cells in advanced systemic mastocytosis and
      synergizes with midostaurin and dasatinib in inducing growth arrest in neoplastic
      mast cells. 

PMID- 23539539
TI  - Hematologic and hemorheological determinants of resting and exercise-induced
      hemoglobin oxygen desaturation in children with sickle cell disease.
AB  - The aim of the study was to determine the factors associated with resting and
      exercise-induced hemoglobin oxygen desaturation. The well-established six-minute
      walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C
      disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen
      saturation was measured before and immediately after the six-minute walk test.
      Blood samples were obtained on the same day to measure hematologic and
      hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was
      defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the
      six-minute walk test compared to resting levels. No children with sickle
      hemoglobin C disease, but approximately 50% of children with sickle cell anemia
      showed mild or moderate oxygen desaturation at rest, which was independently
      associated with the percentage of reticulocytes. Exercise-induced hemoglobin
      oxygen desaturation was observed in 18% of children with sickle hemoglobin C
      disease and 34% of children with sickle cell anemia, and was independently
      associated with the six-minute walk test, acute chest syndrome rate and the
      strength of red blood cell aggregates in children with sickle cell anemia. No
      association was found in children with sickle hemoglobin C disease between
      exercise-induced hemoglobin oxygen desaturation and the measured parameters.
      Hemoglobin oxygen desaturation at rest was common in children with sickle cell
      anemia but not in children with sickle hemoglobin C disease, and was mainly
      associated with greater hemolysis. Physiological strain during exercise and red
      blood cell aggregation properties may predict the occurrence of exercise-induced
      hemoglobin oxygen desaturation in children with sickle cell anemia.

PMID- 23539540
TI  - Impact of disease status and stem cell source on the results of reduced intensity
      conditioning transplant for Hodgkin's lymphoma: a retrospective study from the
      French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).
AB  - The role of reduced intensity allogeneic stem cell transplantation for the
      treatment of relapsed/refractory Hodgkin's lymphoma remains controversial. We
      retrospectively analyzed 191 patients who underwent reduced intensity allogeneic
      stem cell transplantation between 1998 and 2008 for relapsed or refractory
      Hodgkin's lymphoma and whose data were reported to the French registry. The
      median follow-up was 36 months. The estimated 3-year overall survival rate,
      progression-free survival rate, cumulative incidence of relapse and cumulative
      incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively.
      There was no difference in outcome between patients in complete response and in
      partial response at the time of transplantation with regards to overall survival
      (70% versus 74%, no significant difference) and progression-free survival (51%
      versus 42%, no significant difference). Patients with chemoresistant disease had
      a shorter overall survival (39% at 3 years; P=0.0003) and progression-free
      survival (18% at 3 years; P=0.001) than patients in complete remission. The use
      of umbilical cord blood as the source of stem cells was associated with a poor
      outcome with an increased risk of death with a hazard ratio of 3.49 (95%
      confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was
      associated with a better outcome for patients who where alive 1 year after
      transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to
      0.83; P=0.016). Disease status at transplantation remains the most important risk
      factor for outcome. Our data suggest that the use of peripheral blood should be
      preferred whereas umbilical cord blood should be used with caution. 

PMID- 23539541
TI  - HOXA/PBX3 knockdown impairs growth and sensitizes cytogenetically normal acute
      myeloid leukemia cells to chemotherapy.
AB  - The cytogenetically normal subtype of acute myeloid leukemia is associated with
      an intermediate risk which complicates therapeutic options. Lower overall
      HOX/TALE expression appears to correlate with more favorable prognosis/better
      response to treatment in some leukemias and solid cancer. The functional
      significance of the associated gene expression and response to chemotherapy is
      not known. Three independent microarray datasets obtained from large cohorts of
      patients along with quantitative polymerase chain reaction validation were used
      to identify a four-gene HOXA/TALE signature capable of prognostic stratification.
      Biochemical analysis was used to identify interactions between the four encoded
      proteins and targeted knockdown used to examine the functional importance of
      sustained expression of the signature in leukemia maintenance and response to
      chemotherapy. An 11 HOXA/TALE code identified in an intermediate-risk group of
      patients (n=315) compared to a group with a favorable risk (n=105) was reduced to
      a four-gene signature of HOXA6, HOXA9, PBX3 and MEIS1 by iterative analysis of
      independent platforms. This signature maintained the favorable/intermediate risk
      partition and where applicable, correlated with overall survival in
      cytogenetically normal acute myeloid leukemia. We further showed that cell growth
      and function are dependent on maintained levels of these core genes and that
      direct targeting of HOXA/PBX3 sensitizes cytogenetically normal acute myeloid
      leukemia cells to standard chemotherapy. Together the data support a key role for
      HOXA/TALE in cytogenetically normal acute myeloid leukemia and demonstrate that
      targeting of clinically significant HOXA/PBX3 elements may provide therapeutic
      benefit to patients with this subtype of leukemia. 

PMID- 23539542
TI  - Promotion of Caspase Activation by Caspase-9-mediated Feedback Amplification of
      Mitochondrial Damage.
AB  - Mitochondrial disruption during apoptosis results in the activation of caspase-9
      and a downstream caspase cascade. Triggering this caspase cascade leads to the
      cleavage of anti-apoptotic Bcl-2 family proteins, resulting in feedback
      amplification of mitochondrial disruption. However, whether such a feedback loop
      plays an important role in the promotion of caspase activation and execution of
      apoptosis has not been well established. We observed that mutated Bcl-2 or Bcl-xL
      that are resistant to cleavage by caspases inhibited caspase-9-induced caspase
      activation in human H9 T cells. The release of Smac after the activation of
      caspase-9 was also inhibited by cleavage-resistant Bcl-2 or Bcl-xL. Consistently,
      caspase-9-deficient cells were defective in the release of Smac after induction
      of apoptosis. Moreover, addition of a Smac mimetic overcame the inhibitory
      effects of cleavage-resistant Bcl-2/Bcl-xL, and restored caspase-9-mediated cell
      death. Our data suggest that caspase-9-induced feedback disruption of
      mitochondria plays an important role in promoting the activation of caspases,
      while a defect in this process can be overcome by promoting Smac functions.

PMID- 23539543
TI  - Cardiogenic differentiation of mesenchymal stem cells on elastomeric poly
      (glycerol sebacate)/collagen core/shell fibers.
AB  - AIM: To facilitate engineering of suitable biomaterials to meet the challenges
      associated with myocardial infarction. METHODS: Poly (glycerol sebacate)/collagen
      (PGS/collagen) core/shell fibers were fabricated by core/shell electrospinning
      technique, with core as PGS and shell as collagen polymer; and the scaffolds were
      characterized by scanning electron microscope (SEM), fourier transform infrared
      spectroscopy (FTIR), contact angle and tensile testing for cardiac tissue
      engineering. Collagen nanofibers were also fabricated by electrospinning for
      comparison with core/shell fibers. Studies on cell-scaffold interaction were
      carried out using cardiac cells and mesenchymal stem cells (MSCs) co-culture
      system with cardiac cells and MSCs separately serving as positive and negative
      controls respectively. The co-culture system was characterized for cell
      proliferation and differentiation of MSCs into cardiomyogenic lineage in the co
      culture environment using dual immunocytochemistry. The co-culture cells were
      stained with cardiac specific marker proteins like actinin and troponin and MSC
      specific marker protein CD 105 for proving the cardiogenic differentiation of
      MSCs. Further the morphology of cells was analyzed using SEM. RESULTS:
      PGS/collagen core/shell fibers, core is PGS polymer having an elastic modulus
      related to that of cardiac fibers and shell as collagen, providing natural
      environment for cellular activities like cell adhesion, proliferation and
      differentiation. SEM micrographs of electrospun fibrous scaffolds revealed
      porous, beadless, uniform fibers with a fiber diameter in the range of 380 +/- 77
      nm and 1192 +/- 277 nm for collagen fibers and PGS/collagen core/shell fibers
      respectively. The obtained PGS/collagen core/shell fibrous scaffolds were
      hydrophilic having a water contact angle of 17.9 +/- 4.6 degrees  compared to
      collagen nanofibers which had a contact angle value of 30 +/- 3.2 degrees . The
      PGS/collagen core/shell fibers had mechanical properties comparable to that of
      native heart muscle with a young's modulus of 4.24 +/- 0.7 MPa, while that of
      collagen nanofibers was comparatively higher around 30.11 +/- 1.68 MPa. FTIR
      spectrum was performed to confirm the functional groups present in the
      electrospun scaffolds. Amide I and amide II of collagen were detected at 1638.95
      cm(-1) and 1551.64 cm(-1) in the electrospun collagen fibers and at 1646.22 cm(
      1) and 1540.73 cm(-1) for PGS/collagen core/shell fibers respectively. Cell
      culture studies performed using MSCs and cardiac cells co-culture environment,
      indicated that the cell proliferation significantly increased on PGS/collagen
      core/shell scaffolds compared to collagen fibers and the cardiac marker proteins
      actinin and troponin were expressed more on PGS/collagen core/shell scaffolds
      compared to collagen fibers alone. Dual immunofluorescent staining was performed
      to further confirm the cardiogenic differentiation of MSCs by employing MSC
      specific marker protein, CD 105 and cardiac specific marker protein, actinin. SEM
      observations of cardiac cells showed normal morphology on PGS/collagen fibers and
      providing adequate tensile strength for the regeneration of myocardial
      infarction. CONCLUSION: Combination of PGS/collagen fibers and cardiac cells/MSCs
      co-culture system providing natural microenvironments to improve cell survival
      and differentiation, could bring cardiac tissue engineering to clinical
      application.

PMID- 23539544
TI  - The writing on the wall.
AB  - The biomedical research enterprise in the US has become unsustainable and urgent
      action is needed to address a variety of problems, including a lack of
      innovation, an over-reliance on soft money for faculty salaries, the use of
      graduate students as a source of cheap labour, and a 'holding tank' full of
      talented postdocs with limited career opportunities.

PMID- 23539545
TI  - Middle segmental pancreatectomy: a safe and organ-preserving option for benign
      and low-grade malignant lesions.
AB  - AIM: To study the feasibility and safety of middle segmental pancreatectomy (MSP)
      compared with pancreaticoduodenectomy (PD) and extended distal pancreatectomy
      (EDP). METHODS: We studied retrospectively 36 cases that underwent MSP, 44
      patients who underwent PD, and 26 who underwent EDP with benign or low-grade
      malignant lesions in the mid-portion of the pancreas, between April 2003 and
      December 2009 in Ruijin Hospital. The perioperative outcomes and long-term
      outcomes of MSP were compared with those of EDP and PD. Perioperative outcomes
      included operative time, intraoperative hemorrhage, transfusion, pancreatic
      fistula, intra-abdominal abscess/infection, postoperative bleeding, reoperation,
      mortality, and postoperative hospital time. Long-term outcomes, including tumor
      recurrence, new-onset diabetes mellitus (DM), and pancreatic exocrine
      insufficiency, were evaluated. RESULTS: Intraoperative hemorrhage was 316.1 +/-
      309.6, 852.2 +/- 877.8 and 526.9 +/- 414.5 mL for the MSP, PD and EDP groups,
      respectively (P < 0.05). The mean postoperative daily fasting blood glucose level
      was significantly lower in the MSP group than in the EDP group (6.3 +/- 1.5
      mmol/L vs 7.3 +/- 1.5 mmol/L, P < 0.05). The rate of pancreatic fistula was
      higher in the MSP group than in the PD group (42% vs 20.5%, P = 0.039), all of
      the fistulas after MSP corresponded to grade A (9/15) or B (6/15) and were sealed
      following conservative treatment. There was no significant difference in the mean
      postoperative hospital stay between the MSP group and the other two groups. After
      a mean follow-up of 44 mo, no tumor recurrences were found, only one patient
      (2.8%) in the MSP group vs five (21.7%) in the EDP group developed new-onset
      insulin-dependent DM postoperatively (P = 0.029). Moreover, significantly fewer
      patients in the MSP group than in the PD (0% vs 33.3%, P < 0.001) and EDP (0% vs
      21.7%, P = 0.007) required enzyme substitution. CONCLUSION: MSP is a safe and
      organ-preserving option for benign or low-grade malignant lesions in the neck and
      proximal body of the pancreas.

PMID- 23539546
TI  - Training of mental health peer support workers in a non-western high-income city:
      preliminary evaluation and experience.
AB  - BACKGROUND AND AIMS: Peer support workers are an emerging workforce within the
      mental health system in Hong Kong. The purposes of this paper were to describe
      the development of a peer support training programme and to evaluate its outcome
      from the perspectives of both trainees and the users of services that they
      provided. METHOD: The curriculum consisted of six weeks of coursework on the
      recovery approach and a 24-week paid internship at the Warmline telephone
      service. We gathered feedback from 22 Warmline users. Eighteen trainees were also
      assessed using the three recovery-related psychosocial measures and qualitative
      methods. RESULTS: The Warmline service provided by peer support trainees lessened
      the isolation of service users and raised their hopes. Compared to the baseline,
      the peer support trainees scored marginally higher on the psychosocial measures
      at the end of the training. At post-training evaluation, peer support trainees
      said that they had gained in knowledge, were more hopeful about their own
      recovery, and had developed mutually supportive relationships among themselves
      and with their supervisors. CONCLUSION: The programme shows potential benefits
      for both Warmline service users and trainees. Future studies should compare
      different training methods and examine the implementation of peer support
      services in a non-western cultural context.

PMID- 23539547
TI  - Use of human in vitro skin models for accurate and ethical risk assessment:
      metabolic considerations.
AB  - Several human skin models employing primary cells and immortalized cell lines
      used as monocultures or combined to produce reconstituted 3D skin constructs have
      been developed. Furthermore, these models have been included in European
      genotoxicity and sensitization/irritation assay validation projects. In order to
      help interpret data, Cosmetics Europe (formerly COLIPA) facilitated research
      projects that measured a variety of defined phase I and II enzyme activities and
      created a complete proteomic profile of xenobiotic metabolizing enzymes (XMEs) in
      native human skin and compared them with data obtained from a number of in vitro
      models of human skin. Here, we have summarized our findings on the current
      knowledge of the metabolic capacity of native human skin and in vitro models and
      made an overall assessment of the metabolic capacity from gene expression,
      proteomic expression, and substrate metabolism data. The known low expression and
      function of phase I enzymes in native whole skin were reflected in the in vitro
      models. Some XMEs in whole skin were not detected in in vitro models and vice
      versa, and some major hepatic XMEs such as cytochrome P450-monooxygenases were
      absent or measured only at very low levels in the skin. Conversely, despite
      varying mRNA and protein levels of phase II enzymes, functional activity of
      glutathione S-transferases, N-acetyltransferase 1, and UDP
      glucuronosyltransferases were all readily measurable in whole skin and in vitro
      skin models at activity levels similar to those measured in the liver. These
      projects have enabled a better understanding of the contribution of XMEs to
      toxicity endpoints.

PMID- 23539548
TI  - Children with epilepsy in Africa: recommendations from the International Child
      Neurology Association/African Child Neurology Association Workshop.
AB  - This article presents key findings from the International Child Neurology
      Association/African Child Neurology Association Workshop. The viability of
      international guidelines for the management of children with epilepsy should be
      reviewed within each African country, and adapted to comply with the regional
      capacity. Such recommendations can be used to lobby for resources. More training
      centers should be developed in Africa, so that specialists can be trained within
      Africa, in skills relevant to the continent, in collaboration with "out of
      Africa" visiting-specialists to develop the concept of "train the trainers." At
      least 1 child neurology specialist per 100,000 of the population is required.
      Specific to Africa are the challenges from stigma, prejudice, and misconceptions.
      "Epilepsy teams," inclusive of the traditional healers, would enable management
      of increased numbers of children, and challenge policy such that it is the right
      of the child with epilepsy to have reliable access to appropriate antiepileptic
      drugs, support, and health care equity between the rural and urban settings.

PMID- 23539549
TI  - Metachronous colonic metastasis from pancreatic cancer seven years post
      pancreatoduodenectomy.
AB  - Colonic metastasis from other organs is very rare. Here we report the case of a
      62-year-old man with a history of pancreatoduodenectomy for stage IIB pancreatic
      head cancer performed seven years back. He presented with abdominal distension
      and pain. Under the preoperative diagnosis of bowel obstruction, surgical
      treatment was performed, and a circumferential lesion causing bowel obstruction
      of the ascending colon was detected. A right hemicolectomy with lymph node
      dissection was performed. The specimen showed a 5-cm wall thickening with a
      cobble-stone like appearance of the ascending colon, which morphologically
      appeared scirrhous. Histological examination revealed cancer nests invading from
      the subserosa to the muscular and submucosal layers of the colon.
      Immunohistochemical analysis of the tumor cells demonstrated positive staining
      for cytokeratin 7, but negative for cytokeratin 20, which was the same as the
      previous pancreatic cancer specimen. These pathological and immunohistochemical
      features strongly supported the diagnosis of colonic metastasis from the
      pancreas. Thereafter, the patient received systemic chemotherapy, but
      unfortunately, he died 14 mo after the surgery.

PMID- 23539552
TI  - The SYNTAX score and its clinical implications.

PMID- 23539553
TI  - CHADS2 and CHA2DS2-VASc score to assess risk of stroke and death in patients
      paced for sick sinus syndrome.
AB  - OBJECTIVE: The risk of stroke in patients with atrial fibrillation (AF) can be
      assessed by use of the CHADS2 and the CHA2DS2-VASc score system. We hypothesised
      that these risk scores and their individual components could also be applied to
      patients paced for sick sinus syndrome (SSS) to evaluate risk of stroke and
      death. DESIGN: Prospective cohort study. SETTINGS: All Danish pacemaker centres
      and selected centres in the UK and Canada. PATIENTS: Risk factors were recorded
      prior to pacemaker implantation in 1415 patients with SSS participating in the
      Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual
      Chamber Pacing in Sick Sinus Syndrome (Danpace) trial. Development of stroke was
      assessed at follow-up visits and by evaluation of patient charts. Mortality was
      assessed from the civil registration system. INTERVENTIONS: Patients were
      randomised to AAIR (N = 707) or DDDR pacing (N = 708). MAIN OUTCOME MEASURES:
      Stroke and death during follow-up. RESULTS: Mean follow-up was 4.3 +/- 2.5 years.
      In the AAIR group 6.9% patients developed stroke versus 6.1% in the DDDR group
      (NS). There was a significant association between CHADS2 score and the
      development of stroke (HR 1.41; 95% CI 1.22 to 1.64, p < 0.001). CHA2DS2-VASc
      score was also significantly associated with stroke (HR 1.25; CI 1.12 to 1.40, p
      < 0.001). CHADS2 score (HR 1.46; CI 1.36 to 1.56, p < 0.001) and CHA2DS2-VASc
      score (HR 1.39; CI 1.31 to 1.46, p < 0.001) were associated with mortality.
      Results were still significant after adjusting for AF and anticoagulation
      therapy. CONCLUSIONS: CHADS2 and CHA2DS2-VASc score are associated with increased
      risk of stroke and death in patients paced for SSS irrespective of the presence
      of AF.

PMID- 23539554
TI  - Miscarriage and future maternal cardiovascular disease: a systematic review and
      meta-analysis.
AB  - CONTEXT: The 2011 American Heart Association guidelines identified pregnancy
      complications as a risk factor for cardiovascular disease in women. However,
      miscarriage was not mentioned within the guidelines, and there is no consensus on
      the association between miscarriage and future risk of cardiovascular disease.
      OBJECTIVE: To confirm or refute the association, a meta-analysis of published
      papers was conducted. DATA SOURCES: PubMed, Web of Knowledge and Scopus were
      systematically searched to identify appropriate articles. Reference lists were
      then hand searched for additional relevant titles. STUDY SELECTION: To be
      included, articles had to assess the association between miscarriage and
      subsequent cardiovascular disease in otherwise healthy women. Only women who had
      miscarriages were considered exposed. Pooled association measures, using random
      effects meta-analysis, were calculated for coronary heart disease and
      cerebrovascular disease. Publication bias and between-study heterogeneity were
      evaluated. DATA EXTRACTION: Two authors individually reviewed all studies and
      extracted data on patient and study characteristics along with cardiovascular
      outcomes. RESULTS: 10 studies were identified, with 517 504 individuals included
      in the coronary heart disease meta-analysis and 134 461 individuals in the
      cerebrovascular disease analysis. A history of miscarriage was associated with a
      greater odds of developing coronary heart disease, OR (95% CI) =1.45 (1.18 to
      1.78), but not with cerebrovascular disease, OR=1.11 (0.72 to 1.69). There was a
      strong association between recurrent miscarriage and coronary heart disease
      OR=1.99 (1.13 to 3.50). Evidence was found for moderate between-study
      heterogeneity and publication bias in the coronary heart disease analysis.
      CONCLUSIONS: The meta-analysis indicates that a history of miscarriage or
      recurrent miscarriage is associated with a greater risk of subsequent coronary
      heart disease.

PMID- 23539555
TI  - State of the evidence: mechanical ventilation with PEEP in patients with
      cardiogenic shock.
AB  - The need to provide invasive mechanical ventilatory support to patients with
      myocardial infarction and acute left heart failure is common. Despite the large
      number of patients requiring mechanical ventilation in this setting, there are
      remarkably few data addressing the ideal mode of respiratory support in such
      patients. Although there is near universal acceptance regarding the use of non
      invasive positive pressure ventilation in patients with acute pulmonary oedema,
      there is more concern with invasive positive pressure ventilation owing to its
      more significant haemodynamic impact. Positive end-expiratory pressure (PEEP) is
      almost universally applied in mechanically ventilated patients due to benefits in
      gas exchange, recruitment of alveolar units, counterbalance of hydrostatic forces
      leading to pulmonary oedema and maintenance of airway patency. The limited
      available clinical data suggest that a moderate level of PEEP is safe to use in
      severe left ventricular (LV) dysfunction and cardiogenic shock, and may provide
      haemodynamic benefits as well in LV failure which exhibits afterload-sensitive
      physiology. 

PMID- 23539556
TI  - Clinical outcomes after percutaneous or surgical revascularisation of unprotected
      left main coronary artery-related acute myocardial infarction: a single-centre
      experience.
AB  - OBJECTIVES: We evaluated 30-day and 1-year clinical outcomes after percutaneous
      or surgical coronary revascularisation in patients with unprotected left main
      coronary artery (ULMCA)-related acute myocardial infarction (AMI). DESIGN: Single
      centre registry. PATIENTS: Between January 1998 and December 2008, 84 patients
      with ULMCA-related AMI underwent revascularisation treatment in our institution
      (55 underwent percutaneous coronary intervention (PCI), 29 underwent coronary
      artery bypass graft surgery (CABG)). METHODS: One-year clinical follow-up was
      obtained for all patients. Univariable and multivariable analyses were performed
      to find predictors for 30-day mortality and treatment allocation. RESULTS: In the
      PCI-group, all-cause mortality was 64% at 30 days and 69% at 1 year. In the CABG
      group, this was 24% at 30 days and 1 year. Independent predictors of 30-day
      mortality were cardiogenic shock (HR 2.83), thrombolysis in MI (TIMI) 0/1 flow
      (HR 2.27) and diabetes mellitus (HR 2.65). Treatment allocation to PCI was
      primarily determined by TIMI 0/1 flow on baseline angiogram (OR 150). In patients
      with TIMI 2/3 flow on initial angiogram, treatment allocation was determined by
      presentation with cardiogenic shock (OR 5.61), year of inclusion (OR 1.72), and
      distal/bifurcation disease (OR 0.11). CONCLUSIONS: Thirty-day mortality was high
      in patients presenting with an ULMCA-related AMI, both in the PCI as in the CABG
      treatment group. Presentation with cardiogenic shock, TIMI 0/1 flow on initial
      angiogram and diabetes mellitus were independently predicting of 30-day
      mortality, whereas treatment allocation was primarily determined by presentation
      with TIMI 0/1 flow.

PMID- 23539557
TI  - Inference for modulated stationary processes.
AB  - We study statistical inferences for a class of modulated stationary processes
      with time-dependent variances. Due to non-stationarity and the large number of
      unknown parameters, existing methods for stationary or locally stationary time
      series are not applicable. Based on a self-normalization technique, we address
      several inference problems, including self-normalized central limit theorem, self
      normalized cumulative sum test for the change-point problem, long-run variance
      estimation through blockwise self-normalization, and self-normalization-based
      wild boot-strap. Monte Carlo simulation studies show that the proposed self
      normalization-based methods outperform stationarity-based alternatives. We
      demonstrate the proposed methodology using two real data sets: annual mean
      precipitation rates in Seoul during 1771-2000, and quarterly U.S. Gross National
      Product growth rates during 1947-2002.

PMID- 23539558
TI  - Advanced BMP gene therapies for temporal and spatial control of bone
      regeneration.
AB  - Spatial and temporal patterns of bone morphogenetic protein (BMP) signaling are
      crucial to the assembly of appropriately positioned and shaped bones of the face
      and head. This review advances the hypothesis that reconstitution of such
      patterns with cutting-edge gene therapies will transform the clinical management
      of craniofacial bone defects attributed to trauma, disease, or surgical
      resection. Gradients in BMP signaling within developing limbs and orofacial
      primordia regulate proliferation and differentiation of mesenchymal progenitors.
      Similarly, vascular and mesenchymal cells express BMPs in various places and at
      various times during normal fracture healing. In non-healing fractures of long
      bones, BMP signaling is severely attenuated. Devices that release recombinant
      BMPs promote healing of bone in spinal fusions and, in some cases, of open
      fractures, but cannot control the timing and localization of BMP release. Gene
      therapies with regulated expression systems may provide substantial improvements
      in efficacy and safety compared with protein-based therapies. Synthetic gene
      switches, activated by pharmacologics or light or hyperthermic stimuli, provide
      several avenues for the non-invasive regulation of the expression of BMP
      transgenes in both time and space. Through new gene therapy platforms such as
      these, active control over BMP signaling can be achieved to accelerate bone
      regeneration.

PMID- 23539560
TI  - Dental X-rays and risk of meningioma: anatomy of a case-control study.

PMID- 23539559
TI  - Host susceptibility to periodontitis: mapping murine genomic regions.
AB  - Host susceptibility to periodontal infection is controlled by genetic factors. As
      a step toward identifying and cloning these factors, we generated an A/J x
      BALB/cJ F2 mouse resource population. A genome-wide search for Quantitative Trait
      Loci (QTL) associated with periodontitis was performed. We aimed to quantify the
      phenotypic response of the progenies to periodontitis by microCT analysis, to
      perform a genome-wide search for QTL associated with periodontitis, and, finally,
      to suggest candidate genes for periodontitis. We were able to produce 408 F2
      mice. All mice were co-infected with Porphyromonas gingivalis and Fusobacterium
      nucleatum bacteria. Six weeks following infection, alveolar bone loss was
      quantified by computerized tomography (microCT) technology. We found normal
      distribution of the phenotype, with 2 highly significant QTL on chromosomes 5 and
      3. A third significant QTL was found on chromosome 1. Candidate genes were
      suggested, such as Toll-like receptors (TLR) 1 and 6, chemokines, and bone
      remodeling genes (enamelin, ameloblastin, and amelotin). This report shows that
      periodontitis in mice is a polygenic trait with highly significant mapped QTL.

PMID- 23539561
TI  - Challenges, strategies, and gender relations among parents of children recently
      diagnosed with type 1 diabetes.
AB  - This study explored (a) parents' process of changes and challenges in their
      patterns of daily activities after the onset of diabetes in their children; and
      (b) how personal gender relations can restrain or create functional strategies
      for managing the changes and challenges of illness. Interviews were conducted
      with 21 mothers and 15 fathers of 23 children with type 1 diabetes 8 to 10 months
      after onset. Using a constant comparative analysis method, the core category
      depicts how the illness forced parents to reconstruct their family project with
      respect to patterns of daily activities and gender structures. The emerging
      subcategories of reinforced mothering and adjusted fathering illustrate the
      parents' effort to handle contemporary and contradictory demands. With increased
      knowledge of the dynamics of gender relations of families in the context of a
      child's illness, health care professionals can assist in promoting well-being and
      functional strategies in families when a child is newly diagnosed with diabetes.

PMID- 23539562
TI  - Quality colonoscopy: a matter of time, technique or technology?
AB  - Quality colonoscopy is defined by the detection of adenomatous polyps at least
      25% of the time in men and 15% of the time in women. Recent studies highlight the
      importance of key aspects of high quality colonoscopy. These include the amount
      of time spent examining the mucosa or withdrawal time, the quality of withdrawal
      technique and new technologies which seek to maximize the detection of colonic
      neoplasia. This review summarizes the latest evidence regarding the role of time,
      technique and technology in shaping the quality of colonoscopy.

PMID- 23539564
TI  - Vertical and lateral workplace bullying in nursing: development of the hospital
      aggressive behaviour scale.
AB  - Healthcare staff is one of the professional groups that suffers the highest
      exposure to sources of occupational stress such as hostility from coworkers and
      superiors. In order to contribute to the assessment of bullying behaviors in the
      healthcare sector and to obtain a brief and manageable instrument for the
      assessment of this psychosocial risk, we developed the Hospital Aggressive
      Behaviour Scale-version Co-workers-Superiors (HABS-CS). By means of thorough
      qualitative analysis, an initial pool of 166 items was obtained, which were
      reviewed according to precise criteria until concluding with a total of 57 items,
      which were administered to a sample of 1,484 healthcare professionals from 11
      public hospitals. The analyses concluded with the selection of 17 items
      distributed in two subscales. The internal 5-factor structure is the result of
      exploratory and confirmatory factor analysis conducted in two samples. Both the
      resulting questionnaire and the factors identified present adequate psychometric
      properties: high-internal consistency (Cronbach's alpha of .86) and adequate
      criterion validity, analyzed by means of significant correlations between the
      HABS-CS and job satisfaction, burnout components, and psychological well-being.
      This instrument may be of great utility for the assessment and prevention of
      psychosocial risks. 

PMID- 23539563
TI  - The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinosis (NCL), commonly referred to as Batten disease, is
      a group of autosomal recessive neurodegenerative diseases of childhood
      characterized by seizures, blindness, motor and cognitive decline and premature
      death. Currently, there are over 400 known mutations in 14 different genes,
      leading to five overlapping clinical variants of NCL. A large portion of these
      mutations lead to premature stop codons (PTCs) and are predicted to predispose
      mRNA transcripts to nonsense-mediated decay (NMD). Nonsense-mediated decay is
      associated with a number of other genetic diseases and is an important regulator
      of disease pathogenesis. We contend that NMD targets PTCs in NCL gene transcripts
      for degradation. A number of PTC mutations in CLN1, CLN2 and CLN3 lead to a
      significant decrease in mRNA transcripts and a corresponding decrease in protein
      levels and function in patient-derived lymphoblast cell lines. Inhibiting NMD
      leads to an increased transcript level, and where protein function is known,
      increased activity. Treatment with read-through drugs also leads to increased
      protein function. Thus, NMD provides a promising therapeutic target that would
      allow read-through of transcripts to enhance protein function and possibly
      ameliorate Batten disease pathogenesis.

PMID- 23539565
TI  - Identification of differentially expressed genes in microarray data in a
      principal component space.
AB  - Microarray experiments are often conducted in order to compare gene expression
      between two conditions. Tests to detected mean differential expression of genes
      between conditions are conducted applying correction for multiple testing.
      Seldom, relationships between gene expression and microarray conditions are
      investigated in a multivariate approach. Here we propose determining the
      relationship between genes and conditions using a Principal Component Analysis
      (PCA) space and classifying genes to one of two biological conditions based on
      their position relative to a direction on the PC space representing each
      condition. 

PMID- 23539566
TI  - Grappling with cancer.

PMID- 23539572
TI  - Military research. A midcourse correction for U.S. missile defense system.

PMID- 23539571
TI  - Genome sequencing. Return of unexpected DNA results urged.

PMID- 23539573
TI  - U.S. budget. Congress limits NSF funding for political science.

PMID- 23539574
TI  - U.S. budget. U.S. science agencies finally have (reduced) budgets for this year.

PMID- 23539575
TI  - Cosmology. Universe's high-def baby picture confirms standard theory.

PMID- 23539576
TI  - Decade of the monster.

PMID- 23539577
TI  - Marine conservation. As threats to corals grow, hints of resilience emerge.

PMID- 23539578
TI  - Misuse of scientific data in wolf policy.

PMID- 23539579
TI  - Biodiversity depends on logging recovery time.

PMID- 23539580
TI  - Comment on "Nuclear genomic sequences reveal that polar bears are an old and
      distinct bear lineage".
AB  - Based on nuclear and mitochondrial DNA, Hailer et al. (Reports, 20 April 2012, p.
      344) suggested early divergence of polar bears from a common ancestor with brown
      bears and subsequent introgression. Our population genetic analysis that traces
      each of the genealogies in the independent nuclear loci does not support the
      evolutionary model proposed by the authors.

PMID- 23539581
TI  - Response to comment on "Nuclear genomic sequences reveal that polar bears are an
      old and distinct bear lineage".
AB  - Nakagome et al. reanalyzed some of our data and assert that we cannot refute the
      mitochondrial DNA-based scenario for polar bear evolution. Their single-locus
      test statistic is strongly affected by introgression and incomplete lineage
      sorting, whereas our multilocus approaches are better suited to recover the true
      species relationships. Indeed, our sister-lineage model receives high support in
      a Bayesian model comparison.

PMID- 23539584
TI  - Environment and development. Measuring China's circular economy.

PMID- 23539585
TI  - Ecology. Fungal carbon sequestration.

PMID- 23539586
TI  - Biochemistry. A protease for the ages.

PMID- 23539587
TI  - Chemistry. FRETting over the spectroscopic ruler.

PMID- 23539588
TI  - Computer science. Toward a green Internet.

PMID- 23539589
TI  - Neuroscience. Neural stem cells, excited.

PMID- 23539590
TI  - IBI* series winner. Integrating inquiry-based teaching with faculty research.

PMID- 23539591
TI  - Cancer genomics. A medical renaissance? Introduction.

PMID- 23539592
TI  - Steering cancer genomics into the fast lane.

PMID- 23539593
TI  - The downside of diversity.

PMID- 23539595
TI  - Diagnostic cancer genome sequencing and the contribution of germline variants.
AB  - Whole-genome sequencing (WGS) is revolutionizing medical research and has the
      potential to serve as a powerful and cost-effective diagnostic tool in the
      management of cancer. We review the progress to date in the use of WGS to reveal
      how germline variants and mutations may be associated with cancer. We use
      colorectal cancer as an example of how the current level of knowledge can be
      translated into predictions of predisposition. We also address challenges in the
      clinical implementation of the variants in germline DNA identified through cancer
      genome sequencing. We call for the international development of standards to
      facilitate the clinical use of germline information arising from diagnostic
      cancer genome sequencing.

PMID- 23539596
TI  - Cancer pharmacogenomics: early promise, but concerted effort needed.
AB  - The past decade has brought together substantial advances in human genome
      analysis and a maturation of understanding of tumor biology. Although there is
      much progress still to be made, there are now several prominent examples in which
      tumor-associated somatic mutations have been used to identify cellular signaling
      pathways in tumors. This in turn has led to the development of targeted
      therapies, with somatic mutations serving as genomic predictors of tumor response
      and providing new leads for drug development. There is also a realization that
      germline DNA variants can help optimize cancer drug dosing and predict the
      susceptibility of patients to the adverse side effects of these drugs-knowledge
      that ultimately can be used to improve the benefit:risk ratio of cancer treatment
      for individual patients.

PMID- 23539594
TI  - Cancer genome landscapes.
AB  - Over the past decade, comprehensive sequencing efforts have revealed the genomic
      landscapes of common forms of human cancer. For most cancer types, this landscape
      consists of a small number of "mountains" (genes altered in a high percentage of
      tumors) and a much larger number of "hills" (genes altered infrequently). To
      date, these studies have revealed ~140 genes that, when altered by intragenic
      mutations, can promote or "drive" tumorigenesis. A typical tumor contains two to
      eight of these "driver gene" mutations; the remaining mutations are passengers
      that confer no selective growth advantage. Driver genes can be classified into 12
      signaling pathways that regulate three core cellular processes: cell fate, cell
      survival, and genome maintenance. A better understanding of these pathways is one
      of the most pressing needs in basic cancer research. Even now, however, our
      knowledge of cancer genomes is sufficient to guide the development of more
      effective approaches for reducing cancer morbidity and mortality.

PMID- 23539598
TI  - Topology-driven magnetic quantum phase transition in topological insulators.
AB  - The breaking of time reversal symmetry in topological insulators may create
      previously unknown quantum effects. We observed a magnetic quantum phase
      transition in Cr-doped Bi2(SexTe1-x)3 topological insulator films grown by means
      of molecular beam epitaxy. Across the critical point, a topological quantum phase
      transition is revealed through both angle-resolved photoemission measurements and
      density functional theory calculations. We present strong evidence that the bulk
      band topology is the fundamental driving force for the magnetic quantum phase
      transition. The tunable topological and magnetic properties in this system are
      well suited for realizing the exotic topological quantum phenomena in magnetic
      topological insulators.

PMID- 23539597
TI  - Epigenetic reprogramming in cancer.
AB  - The demonstration of induced pluripotency and direct lineage conversion has led
      to remarkable insights regarding the roles of transcription factors and chromatin
      regulators in mediating cell state transitions. Beyond its considerable
      implications for regenerative medicine, this body of work is highly relevant to
      multiple stages of oncogenesis, from the initial cellular transformation to the
      hierarchical organization of established malignancies. Here, we review conceptual
      parallels between the respective biological phenomena, highlighting important
      interrelationships among transcription factors, chromatin regulators, and
      preexisting epigenetic states. The shared mechanisms provide insights into
      oncogenic transformation, tumor heterogeneity, and cancer stem cell models.

PMID- 23539599
TI  - Tuning selectivity in propylene epoxidation by plasmon mediated photo-switching
      of Cu oxidation state.
AB  - Oxidation of functioning copper has restricted its applicability as a catalyst
      for commercially important epoxidation of propylene to form propylene oxide.
      Here, we report that steady-state selectivity in propylene epoxidation on copper
      (Cu) nanoparticles increases sharply when the catalyst is illuminated with
      visible light. The selectivity increase is accompanied by light-induced reduction
      of the surface Cu atoms, which is brought about by photoexcitation of the
      localized surface plasmon resonance (LSPR) of Cu. We discuss multiple mechanisms
      by which Cu LSPR weakens the Cu-O bonds, reducing Cu2O.

PMID- 23539600
TI  - Photoredox activation for the direct beta-arylation of ketones and aldehydes.
AB  - The direct beta-activation of saturated aldehydes and ketones has long been an
      elusive transformation. We found that photoredox catalysis in combination with
      organocatalysis can lead to the transient generation of 5pi-electron beta
      enaminyl radicals from ketones and aldehydes that rapidly couple with cyano
      substituted aryl rings at the carbonyl beta-position. This mode of activation is
      suitable for a broad range of carbonyl beta-functionalization reactions and is
      amenable to enantioselective catalysis.

PMID- 23539601
TI  - Direct observations of the evolution of polar cap ionization patches.
AB  - Patches of ionization are common in the polar ionosphere, where their motion and
      associated density gradients give variable disturbances to high-frequency (HF)
      radio communications, over-the-horizon radar location errors, and disruption and
      errors to satellite navigation and communication. Their formation and evolution
      are poorly understood, particularly under disturbed space weather conditions. We
      report direct observations of the full evolution of patches during a geomagnetic
      storm, including formation, polar cap entry, transpolar evolution, polar cap
      exit, and sunward return flow. Our observations show that modulation of nightside
      reconnection in the substorm cycle of the magnetosphere helps form the gaps
      between patches where steady convection would give a "tongue" of ionization
      (TOI).

PMID- 23539602
TI  - Structure of the integral membrane protein CAAX protease Ste24p.
AB  - Posttranslational lipidation provides critical modulation of the functions of
      some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached
      to cysteine residues in proteins containing C-terminal CAAX sequence motifs
      (where A is an aliphatic residue and X is any residue). Isoprenylation is
      followed by cleavage of the AAX amino acid residues and, in some cases, by
      additional proteolytic cuts. We determined the crystal structure of the CAAX
      protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the
      maturation of yeast mating pheromone a-factor. The Ste24p core structure is a
      ring of seven transmembrane helices enclosing a voluminous cavity containing the
      active site and substrate-binding groove. The cavity is accessible to the
      external milieu by means of gaps between splayed transmembrane helices. We
      hypothesize that cleavage proceeds by means of a processive mechanism of
      substrate insertion, translocation, and ejection.

PMID- 23539603
TI  - The structural basis of ZMPSTE24-dependent laminopathies.
AB  - Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases
      of lamin processing (laminopathies), such as the premature aging disease progeria
      and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the
      nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of
      this processing results in accumulation of farnesylated, membrane-associated
      prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven
      transmembrane alpha-helical barrel structure, surrounding a large, water-filled,
      intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic
      site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM
      tetrapeptide showed that the mode of binding of the substrate resembles that of
      an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated
      mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease
      peptide-binding site and to the bottom of the chamber.

PMID- 23539604
TI  - Roots and associated fungi drive long-term carbon sequestration in boreal forest.
AB  - Boreal forest soils function as a terrestrial net sink in the global carbon
      cycle. The prevailing dogma has focused on aboveground plant litter as a
      principal source of soil organic matter. Using (14)C bomb-carbon modeling, we
      show that 50 to 70% of stored carbon in a chronosequence of boreal forested
      islands derives from roots and root-associated microorganisms. Fungal biomarkers
      indicate impaired degradation and preservation of fungal residues in late
      successional forests. Furthermore, 454 pyrosequencing of molecular barcodes, in
      conjunction with stable isotope analyses, highlights root-associated fungi as
      important regulators of ecosystem carbon dynamics. Our results suggest an
      alternative mechanism for the accumulation of organic matter in boreal forests
      during succession in the long-term absence of disturbance.

PMID- 23539605
TI  - The biological underpinnings of Namib Desert fairy circles.
AB  - The sand termite Psammotermes allocerus generates local ecosystems, so-called
      fairy circles, through removal of short-lived vegetation that appears after rain,
      leaving circular barren patches. Because of rapid percolation and lack of
      evapotranspiration, water is retained within the circles. This process results in
      the formation of rings of perennial vegetation that facilitate termite survival
      and locally increase biodiversity. This termite-generated ecosystem persists
      through prolonged droughts lasting many decades.

PMID- 23539606
TI  - ESCRT-III assembly and cytokinetic abscission are induced by tension release in
      the intercellular bridge.
AB  - The last step of cell division, cytokinesis, produces two daughter cells that
      remain connected by an intercellular bridge. This state often represents the
      longest stage of the division process. Severing the bridge (abscission) requires
      a well-described series of molecular events, but the trigger for abscission
      remains unknown. We found that pulling forces exerted by daughter cells on the
      intercellular bridge appear to regulate abscission. Counterintuitively, these
      forces prolonged connection, whereas a release of tension induced abscission.
      Tension release triggered the assembly of ESCRT-III (endosomal sorting complex
      required for transport-III), which was followed by membrane fission. This
      mechanism may allow daughter cells to remain connected until they have settled in
      their final locations, a process potentially important for tissue organization
      and morphogenesis.

PMID- 23539607
TI  - Is test anxiety a peril for students with intellectual disabilities?
AB  - Test anxiety is one of the most confronting issues in modern times with the
      increase in the number of standardised and high-stakes testing. Research has
      established that there is a direct link between test anxiety and cognitive
      deficits. The aim of this study is to determine the test anxiety scores of the
      students with intellectual disabilities in South Australia. It also provided
      insights into the reasons for high-test anxiety in the participants under study.
      The Spielberger's Test Anxiety Questionnaire was administered on students with
      intellectual disabilities in stage 1. Interviews were conducted with participants
      with intellectual disabilities, parents and teachers in stage 2. Questionnaire
      findings revealed that the majority of the adolescent females and males and all
      adult females with intellectual disabilities had high test anxiety scores.
      However, the majority of adult males with intellectual disabilities obtained
      moderate test anxiety scores. In the worry and emotionality subscales, it was
      also found that the majority of adolescents and adults with intellectual
      disabilities were found to score high. The high test anxiety scores have been
      justified by the interview responses obtained from the three groups of
      respondents. A number of factors have been identified to be the major predictors
      of test anxiety in students with intellectual disabilities.

PMID- 23539608
TI  - A pilot survey of physical activity in men with an intellectual disability.
AB  - People with intellectual disability (ID) are reported as a sedentary population
      with increased risks of poor health due to an inactive and sedentary lifestyle.
      As the benefits of physical activity are acknowledged, measuring physical
      activity accurately is important to help identify reasons for low and high
      physical activity in order to assist and maintain recommended levels for optimal
      health. This article reports a pilot study undertaken to validate the use of a
      physical activity monitor (Sensewear Armband) and the International Physical
      Activity Questionnaire (IPAQ) as instruments for measuring and exploring physical
      activity of men with ID. The design was a one-group descriptive study and the
      data were collected over a 7-day period from 17 men. The Sensewear Armband
      enabled continuous and long-term measurement of 14 objective physical activity
      metrics. The IPAQ examined details of physical activity reported over 7 days.
      Equivalent results were obtained from both the instruments, indicating a positive
      correlation between the Sensewear Armband and the IPAQ. The results show 50% have
      low activity levels, and the national recommended physical activity levels have
      been achieved at a very low active intensity. No sustainable high physical
      activity intensity levels were recorded. The results confirmed the Sensewear
      Armband and the IPAQ as a practical means of measuring and understanding physical
      activity levels in men with ID.

PMID- 23539609
TI  - Experimental study on strength evaluation applied for teeth extraction: an in
      vivo study.
AB  - PURPOSE: The aim of this work was to analyse all the applied movements when
      extracting healthy upper and lower jaw premolars for orthodontic purposes. The
      authors wanted to demonstrate that the different bone densities of the mandible
      and maxilla are not a significant parameter when related to the extraction force
      applied. The buccal and palatal rocking movements, plus the twisting movements
      were also measured in this in-vivo study during premolar extraction for
      orthodontic purposes. METHODS: THE PHYSICAL STRAINS OR FORCES TRANSFERRED ONTO
      THE TEETH DURING EXTRACTION ARE THE FOLLOWING THREE MOVEMENTS: gripping,
      twisting, and traction. A strain measurement gauge was attached onto an ordinary
      dentistry plier. The strain measurement gauge was constituted with an
      extensimetric washer with three 45o grids. The system operation was correlated to
      the variation of electrical resistance. RESULTS: The variations of resistance
      (?R) and all the different forces applied to the teeth (?V) were recorded by a
      computerized system. Data results were processed through Microsoft Excel. The
      results underlined the stress distribution on the extracted teeth during
      gripping, twisting and flexion. CONCLUSIONS: The obtained data showed that the
      strength required to effect teeth extraction is not influenced by the quality of
      the bone but is instead influenced by the shape of the tooth's root.

PMID- 23539610
TI  - Obstetric and neonatal outcome after oocyte donation in 106 women with Turner
      syndrome: a Nordic cohort study.
AB  - STUDY QUESTION: What are the obstetric and neonatal outcomes of deliveries after
      oocyte donation (OD) in women with Turner syndrome (TS)? SUMMARY ANSWER:
      Pregnancies among women with TS carry a substantial risk, particularly for
      hypertensive disorders. Potentially life-threatening complications occurred in
      3.3% of pregnancies. The neonatal outcomes were generally reassuring, with
      similar rates of preterm birth and low birthweight (LBW) as after conventional
      IVF and better than previously reported in deliveries after OD in women with TS.
      WHAT IS KNOWN ALREADY: OD pregnancies in women with TS are known to be high-risk
      pregnancies. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study
      included 106 women with TS who delivered after OD (n = 122 deliveries, n = 131
      newborns) in three Nordic countries (Finland, Denmark, Sweden) between 1992 and
      2011. PARTICIPANTS, SETTING AND METHODS: Women with TS who delivered after OD in
      three Nordic countries were identified (n = 110). Four women declined to
      participate or were lost to follow-up, thus 106 women were included in the study.
      The medical data from fertility clinics, antenatal clinics and the hospitals
      where the women had been treated and/or delivered were scrutinized. MAIN RESULTS
      AND THE ROLE OF CHANCE: In this cohort, the karyotype was 45,X in 44% of the
      women with TS. Ten women (9.4%) had a known cardiac defect before pregnancy.
      Single embryo transfer was performed in 70.3% of the cases and the multiple birth
      rate was 7.4%. In total, 35.0% of the pregnancies were associated with a
      hypertensive disorder including pre-eclampsia in 20.5%. Potentially life
      threatening complications occurred in four pregnancies (3.3%), including one
      woman with aortic dissection, one with mild regurgitation of the tricuspid and
      mitral valve, one with a mechanical heart valve who developed HELLP syndrome
      (haemolysis, elevated liver enzymes, low platelets) and one who underwent a post
      partum hysterectomy due to severe haemorrhaging. Neonatal outcomes were
      reassuring, with a preterm birth rate of 8.0% and LBW rate of 8.8% in singletons.
      Major birth defects were found in 3.8% of the children. The perinatal mortality
      was 2.3% (3/131), including a set of extremely preterm twins. LIMITATIONS,
      REASONS FOR CAUTION: Although this study was performed over a period of almost 20
      years in three different countries, with a low drop-out rate and little missing
      data, much larger series are needed to assess rare events. This study also lacks
      an appropriate control group. WIDER IMPLICATIONS OF THE FINDINGS: This study
      suggests that cardiovascular evaluation before and during pregnancy may
      contribute to favourable obstetric outcomes in many cases. Maternal outcomes were
      in agreement with the literature while neonatal outcomes were generally better
      than previously reported. The outcomes were consistent across the three
      countries, supporting generalizability to similar populations.

PMID- 23539611
TI  - microRNA signature is altered in both human epididymis and seminal microvesicles
      following vasectomy.
AB  - STUDY QUESTION: Does vasectomy impact microRNA (miRNA) expression in the
      epididymis and seminal microvesicles (SMVs) in a non-reversible manner? SUMMARY
      ANSWER: The miRNA signature in the epididymis and SMVs is altered by vasectomy
      and only partially restored after vasovasostomy surgery. WHAT IS KNOWN ALREADY:
      Vasectomy modifies the epididymal transcriptome and triggers non-reversible
      changes that affect sperm function. Some vasovasostomized men experience a
      reduced fertility outcome. STUDY DESIGN, SIZE, DURATION: Human epididymides
      provided by three control donors and three vasectomized donors were collected
      under artificial circulation through Transplant Quebec (Quebec, QC, Canada).
      Semen from three normal, three vasectomized and five vasovasostomized donors was
      provided by the andrology clinic. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Epididymides and semen were collected from donors between 26 and 50 years of age
      with no known pathologies that could potentially affect reproductive function.
      After RNA extraction, epididymal miRNA profiles were determined by microarray
      (Affimetrix), compared by ANOVA and confirmed by real-time PCR. The correlation
      between miRNA and gene expression profiles was investigated by an integrated
      genomic approach. miRNA signature from purified SMVs was established by
      microarray. MAIN RESULTS AND THE ROLE OF CHANCE: Vasectomy significantly modified
      the expression of epididymal miRNAs, which were mainly correlated with mRNAs for
      transcription factors. Vasectomy also impacted the detection of 118 of the miRNAs
      found in SMVs from normal donors, including miRNAs of epididymal origin contained
      in epididymosomes. Among seminal miRNAs changes, 52 were reversible according to
      the expression levels of miRNA in the semen samples from vasovasostomized donors,
      while 66 were non-reversible. LIMITATIONS, REASONS FOR CAUTION: Identification of
      miRNAs responsive to vasectomy was determined with a limited number of samples
      due to the low number of human specimen samples available. WIDER IMPLICATIONS OF
      THE FINDINGS: According to the critical role played by miRNAs in all biological
      systems, we believe that miRNA changes occurring upstream and downstream of the
      vasectomy site may be related to the reduced fertility outcome reported following
      surgically successful vasectomy reversal. This study may provide new tools for
      predicting vasovasostomy success and open avenues for the identification of the
      molecular players involved in male infertility.

PMID- 23539612
TI  - Anti-Mullerian hormone levels in girls and adolescents with Turner syndrome are
      related to karyotype, pubertal development and growth hormone treatment.
AB  - STUDY QUESTION: In girls and adolescents with Turner syndrome (TS), is there a
      correlation between serum AMH levels and karyotype, spontaneous puberty and other
      biochemical markers of ovarian function, or growth hormone (GH) therapy? SUMMARY
      ANSWER: Serum anti-Mullerian hormone (AMH) correlates with karyotype, pubertal
      development, LH, FSH and are measurable in a higher percentage of TS patients
      under GH therapy. WHAT IS KNOWN ALREADY: Most girls with TS suffer from
      incomplete sexual development, premature ovarian failure and infertility due to
      abnormal ovarian folliculogenesis. Serum AMH levels reflect the ovarian reserve
      in females, even in childhood. STUDY DESIGN, SIZE, DURATION: Cross-sectional
      study investigating 270 karyotype proven TS patients aged 0-20 years between 2009
      and 2010. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Studies were conducted at
      three University Children's hospitals in Europe. Main outcome measures were
      clinical data concerning pubertal development as well as laboratory data
      including karyotype, serum AMH, LH, FSH, estradiol (E2), inhibin B and IGF.
      RESULTS AND THE ROLE OF CHANCE: Serum AMH was detectable in 21.9% of all TS girls
      and correlated strongly with karyotypes. A measurable serum AMH was found in 77%
      of TS girls with karyotype 45,X/46,XX, in 25% with 'other' karyotypes and in only
      10% of 45,X TS girls. A strong relationship was also observed for measurable
      serum AMH and signs of spontaneous puberty such as breast development [adjusted
      odds ratio (OR) 19.3; 95% CI 2.1-175.6; P = 0.009] and menarche (crude OR 47.6;
      95% CI 4.8-472.9; P = 0.001). Serum AMH correlated negatively with FSH and LH,
      but did not correlate with E2 and inhibin B. GH therapy increased the odds of
      having measurable AMH in TS (adjusted OR 4.1; 95% CI 1.9-8.8; P < 0.001).
      LIMITATIONS, REASONS FOR CAUTION: The cross-sectional design of the study does
      not allow longitudinal interpretation of the data; for that further studies are
      needed. High percentage of non-measurable AMH levels in the cohort of TS require
      categorized analysis.

PMID- 23539613
TI  - The feasibility of fertility preservation in adolescents with Klinefelter
      syndrome.
AB  - STUDY QUESTION: Is fertility preservation feasible after the onset of puberty in
      adolescents with Klinefelter syndrome (KS)? SUMMARY ANSWER: Fertility
      preservation counseling should be an integral part of the care of XXY
      adolescents. Frozen ejaculated or testicular spermatozoa and even frozen immature
      germ cells can give them the potential to conceive their genetic progeny.
      However, no biological or clinical parameters were predictive of mature or
      immature germ cell retrieval. WHAT IS KNOWN ALREADY: KS is the commonest sex
      chromosome disorder observed in azoospermic infertile males. Testicular sperm
      extraction success decreases with age and after testosterone therapy. Arguably,
      spermatozoa should be retrieved from KS males at the onset of puberty and before
      testosterone therapy to increase the chance of success. STUDY DESIGN, SIZE,
      DURATION: A retrospective study was performed in eight KS adolescents, aged
      between 15 and 17 years, who were referred for counseling about their future
      fertility to the center CECOS (Centre d'Etude et de Conservation des Oeufs et du
      Sperme humain) at Rouen University Hospital between October 2008 and December
      2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients were first seen with
      their parents and then separately. It was proposed to them that they should
      provide a semen sample, if this was azoospermic, two other semen samples spaced
      by 3 months were collected. If azoospermia was confirmed, a bilateral testicular
      biopsy was proposed for sperm retrieval and testicular tissue preservation. Each
      adolescent met the psychologist before undergoing testicular biopsy. Paraffin
      embedded testicular tissue was evaluated after staining with hematoxylin-eosin
      and saffron and immunostaining using vimentin, anti-Mullerian hormone, androgen
      receptor and MAGE-A4 antibodies. Sertoli cell maturity, germ cell identification
      and lamina propria alteration were assessed on seminiferous tubules. MAIN RESULTS
      AND THE ROLE OF CHANCE: KS adolescents were not deeply concerned about their
      future fertility and only became involved in the process of fertility
      preservation after at least three medical consultations. The parents agreed
      immediately that fertility preservation should be attempted. Seven non-mosaic XXY
      adolescents presented with azoospermia and one XXY/XY adolescent had
      oligozoospermia. Increased plasma levels of FSH and LH as well as bilateral
      testicular hypotrophy were observed in all patients. The XXY/XY adolescent banked
      four semen samples before testosterone replacement therapy. Two patients refused
      testicular biopsy. Five patients accepted a bilateral testicular biopsy.
      Spermatozoa were retrieved in one patient, elongated spermatids and spermatocytes
      I in a second patient. LIMITATIONS, REASONS FOR CAUTION: The number of patients
      enrolled in our study was low because the diagnosis of KS is only rarely made
      before or at the onset of puberty. Most XXY males are diagnosed in adulthood
      within the context of male infertility. WIDER IMPLICATIONS OF THE FINDINGS:
      Spermatozoa can be retrieved in semen sample and in testicular tissue of
      adolescent Klinefelter patients. Furthermore, the testis may also harbor
      spermatogonia and incompletely differentiated germ cells. However, the physician
      should discuss with the patient and his parents over a period of several months
      before collecting a semen sample and performing bilateral testicular biopsy.
      Fertility preservation might best be proposed to adolescent Klinefelter patients
      just after the onset of puberty when it is possible to collect a semen sample and
      when the patient is able to consider alternative options to achieve fatherhood
      and also to accept the failure of spermatozoa or immature germ cell retrieval.

PMID- 23539614
TI  - Only ankle-brachial index may not be an accurate information about the prevalence
      of peripheral arterial disease.

PMID- 23539615
TI  - Impact of preprocedural high-sensitivity C-reactive protein on contrast-induced
      nephropathy in patients undergoing primary percutaneous coronary intervention.
AB  - We assessed the impact of preprocedural high-sensitivity C-reactive protein
      (hsCRP) on the incidence of contrast-induced nephropathy (CIN) in patients with
      ST-segment elevation myocardial infarction (STEMI) undergoing primary
      percutaneous coronary intervention (p-PCI). We retrospectively studied 1452
      patients with STEMI undergoing p-PCI. Baseline clinical characteristics, CIN
      incidence, and other inhospital clinical outcomes were compared among hsCRP
      quartiles; 212 (14.6%) patients developed CIN. The overall inhospital mortality
      rate was 4.5% (65 patients). Univariate analysis revealed CIN incidence was
      significantly associated with hsCRP, with 7.44% for quartile Q1 (<3.00 mg/L),
      12.6% for Q2 (3.00-5.90 mg/L), 16.9% for Q3 (5.91-11.4 mg/L), and 21.49% for Q4
      (>11.4 mg/L; P < .001). Patients with a higher hsCRP experienced a higher rate of
      inhospital complications. After adjusting for potential confounders, hsCRP >6.50
      mg/L was significantly associated with the occurrence of CIN. Preprocedural hsCRP
      levels are significantly related to the incidence of CIN in patients with STEMI
      undergoing p-PCI. 

PMID- 23539616
TI  - Heme sensor proteins.
AB  - Heme is a prosthetic group best known for roles in oxygen transport, oxidative
      catalysis, and respiratory electron transport. Recent years have seen the roles
      of heme extended to sensors of gases such as O2 and NO and cell redox state, and
      as mediators of cellular responses to changes in intracellular levels of these
      gases. The importance of heme is further evident from identification of proteins
      that bind heme reversibly, using it as a signal, e.g. to regulate gene expression
      in circadian rhythm pathways and control heme synthesis itself. In this
      minireview, we explore the current knowledge of the diverse roles of heme sensor
      proteins.

PMID- 23539617
TI  - Biosynthesis of the iron-molybdenum cofactor of nitrogenase.
AB  - The iron-molybdenum cofactor (the M-cluster) serves as the active site of
      molybdenum nitrogenase. Arguably one of the most complex metal cofactors in
      biological systems, the M-cluster is assembled through the formation of an 8Fe
      core prior to the insertion of molybdenum and homocitrate into this core. Here,
      we review the recent progress in the research area of M-cluster assembly, with an
      emphasis on our work that provides useful insights into the mechanistic details
      of this process.

PMID- 23539618
TI  - Biosynthesis of the urease metallocenter.
AB  - Metalloenzymes often require elaborate metallocenter assembly systems to create
      functional active sites. The medically important dinuclear nickel enzyme urease
      provides an excellent model for studying metallocenter assembly. Nickel is
      inserted into the urease active site in a GTP-dependent process with the
      assistance of UreD/UreH, UreE, UreF, and UreG. These accessory proteins
      orchestrate apoprotein activation by delivering the appropriate metal,
      facilitating protein conformational changes, and possibly providing a requisite
      post-translational modification. The activation mechanism and roles of each
      accessory protein in urease maturation are the subject of ongoing studies, with
      the latest findings presented in this minireview.

PMID- 23539620
TI  - Thematic minireview series: metals in biology 2013.
AB  - One-half of the available protein structures contain metals, explaining their
      roles as essential trace elements. Metals are also critical in many aspects of
      nucleic acid biochemistry. This prologue briefly introduces the fifth of the
      Thematic Series on Metals in Biology, which began in the Journal of Biological
      Chemistry in 2009. The five minireviews in this 2013 series deal with the
      molybdenum prosthetic group (a pterin known as Moco); the biosynthesis of the "M
      cluster" molybdenum prosthetic group of nitrogenase; the biosynthesis of the
      nickel-based metallocenter of the enzyme urease; several of the processing,
      transport, and medical aspects of cobalamins; and the growing roles of heme
      sensor proteins.

PMID- 23539619
TI  - Navigating the B(12) road: assimilation, delivery, and disorders of cobalamin.
AB  - The reactivity of the cobalt-carbon bond in cobalamins is the key to their
      chemical versatility, supporting both methyl transfer and isomerization
      reactions. During evolution of higher eukaryotes that utilize vitamin B12, the
      high reactivity of the cofactor coupled with its low abundance pressured
      development of an efficient system for uptake, assimilation, and delivery of the
      cofactor to client B12-dependent enzymes. Although most proteins suspected to be
      involved in B12 trafficking were discovered by 2009, the recent identification of
      a new protein reveals that the quest for elucidating the intracellular B12
      highway is still far from complete. Herein, we review the biochemistry of
      cobalamin trafficking.

PMID- 23539621
TI  - Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2
      gene locus.
AB  - BACKGROUND: MATII biosynthesizes AdoMet, which supplies methyl group for
      methylation of molecules, including histone. RESULTS: MATII interacts with
      histone methyltransferase SETDB1 and inhibits COX-2 gene expression. CONCLUSION:
      AdoMet synthesis and histone methylation are coupled on chromatin by a physical
      interaction of MATII and SETDB1 at the MafK target genes. SIGNIFICANCE: MATII may
      be important for both gene-specific and epigenome-wide regulation of histone
      methylation. Methionine adenosyltransferase (MAT) synthesizes S
      adenosylmethionine (AdoMet), which is utilized as a methyl donor in
      transmethylation reactions involving histones. MATIIalpha, a MAT isozyme, serves
      as a transcriptional corepressor in the oxidative stress response and forms the
      AdoMet-integrating transcription regulation module, affecting histone
      methyltransferase activities. However, the identities of genes regulated by
      MATIIalpha or its associated methyltransferases are unclear. We show that
      MATIIalpha represses the expression of cyclooxygenase 2 (COX-2), encoded by
      Ptgs2, by specifically interacting with histone H3K9 methyltransferase SETDB1,
      thereby promoting the trimethylation of H3K9 at the COX-2 locus. We discuss both
      gene-specific and epigenome-wide functions of MATIIalpha.

PMID- 23539622
TI  - Biochemical characterization of molybdenum cofactor-free nitrate reductase from
      Neurospora crassa.
AB  - Nitrate reductase (NR) is a complex molybdenum cofactor (Moco)-dependent
      homodimeric metalloenzyme that is vitally important for autotrophic organism as
      it catalyzes the first and rate-limiting step of nitrate assimilation. Beside
      Moco, eukaryotic NR also binds FAD and heme as additional redox active cofactors,
      and these are involved in electron transfer from NAD(P)H to the enzyme molybdenum
      center where reduction of nitrate to nitrite takes place. We report the first
      biochemical characterization of a Moco-free eukaryotic NR from the fungus
      Neurospora crassa, documenting that Moco is necessary and sufficient to induce
      dimer formation. The molybdenum center of NR reconstituted in vitro from apo-NR
      and Moco showed an EPR spectrum identical to holo-NR. Analysis of mutants unable
      to bind heme or FAD revealed that insertion of Moco into NR occurs independent
      from the insertion of any other NR redox cofactor. Furthermore, we showed that at
      least in vitro the active site formation of NR is an autonomous process.

PMID- 23539623
TI  - The molybdenum cofactor.
AB  - The transition element molybdenum needs to be complexed by a special cofactor to
      gain catalytic activity. Molybdenum is bound to a unique pterin, thus forming the
      molybdenum cofactor (Moco), which, in different variants, is the active compound
      at the catalytic site of all molybdenum-containing enzymes in nature, except
      bacterial molybdenum nitrogenase. The biosynthesis of Moco involves the complex
      interaction of six proteins and is a process of four steps, which also require
      iron, ATP, and copper. After its synthesis, Moco is distributed, involving Moco
      binding proteins. A deficiency in the biosynthesis of Moco has lethal
      consequences for the respective organisms.

PMID- 23539624
TI  - Histone deacetylase inhibitors (HDACis) that release the positive transcription
      elongation factor b (P-TEFb) from its inhibitory complex also activate HIV
      transcription.
AB  - Numerous studies have looked at the effects of histone deacetylase inhibitors
      (HDACis) on HIV reactivation in established transformed cell lines and primary
      CD4(+) T cells. However, their findings remain confusing, and differences between
      effects of class I- and class II-specific HDACis persist. Because no clear
      picture emerged, we decided to determine how HDACis reactivate HIV in transformed
      cell lines and primary cells. We found that neither histone H3 nor tubulin
      acetylation correlated with HIV reactivation in Jurkat and HeLa cells. Rather,
      HDACis that could reactivate HIV in chromatin or on episomal plasmids also
      released free positive transcription elongation factor b (P-TEFb) from its
      inhibitory 7SK snRNP. In resting primary CD4(+) T cells, where levels of P-TEFb
      are vanishingly low, the most potent HDACi, suberoylanilide hydroxyamic acid
      (SAHA), had minimal effects. In contrast, when these cells were treated with a
      PKC agonist, bryostatin 1, which increased levels of P-TEFb, then SAHA once again
      reactivated HIV. We conclude that HDACis, which can reactivate HIV, work via the
      release of free P-TEFb from the 7SK snRNP.

PMID- 23539625
TI  - An intramolecular interaction involving the N terminus of a streptococcal adhesin
      affects its conformation and adhesive function.
AB  - BACKGROUND: P1 is an adhesin on the surface of Streptococcus mutans. RESULTS:
      Destroying the high affinity interaction between the N and C termini of S. mutans
      P1 creates a non-adherent phenotype. CONCLUSION: The N terminus facilitates
      proper folding, function, and stability within recombinant P1. SIGNIFICANCE: The
      relationship between folding, maturation, and cell surface assembly is critical
      to understanding the P1 mechanism of action. The adhesin P1 is localized on the
      surface of the oral pathogen Streptococcus mutans and facilitates an interaction
      with the glycoprotein complex salivary agglutinin that is comprised primarily of
      the scavenger receptor gp340. Recent crystal structures of P1 display an unusual
      structure in which the protein folds back upon itself to form an elongated hybrid
      helical stalk with a globular head at the apex and a globular C-terminal region
      at the base. The N terminus of P1 has not yet been characterized. In this report
      we describe the contribution of an interaction between the N-terminal and C
      terminal portions of the protein that is required for proper function of P1 on
      the surface of S. mutans. Utilizing recombinant N-terminal and C-terminal
      fragments, we employed isothermal titration calorimetry and native gel
      electrophoresis to demonstrate that these fragments form a high affinity and
      stable complex in solution. Furthermore, circular dichroism and surface plasmon
      resonance measurements indicated that the N-terminal fragment contributes to the
      folding and increases the functionality of the C-terminal fragment in trans.
      Finally, we utilized circular dichroism, surface plasmon resonance, and
      differential scanning calorimetry to show that an N-terminal 106-amino acid
      segment within P1 contributes to the proper folding and function of the full
      length recombinant molecule and increases the stability of its elongated hybrid
      helical stalk.

PMID- 23539626
TI  - Wingless-type mammary tumor virus integration site family, member 5A (Wnt5a)
      regulates human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120
      (gp120)-induced expression of pro-inflammatory cytokines via the Ca2+/calmodulin
      dependent protein kinase II (CaMKII) and c-Jun N-terminal kinase (JNK) signaling
      pathways.
AB  - BACKGROUND: HIV-1 infection causes chronic neuroinflammation in the central
      nervous system (CNS). RESULTS: The spinal cytokine up-regulation induced by HIV-1
      gp120 protein depends on Wnt5a/CaMKII and/or Wnt5a/JNK pathways. CONCLUSION:
      gp120 stimulates cytokine expression in the spinal cord dorsal horn by activating
      Wnt5a signaling. SIGNIFICANCE: The finding reveals Wnt signaling-mediated novel
      mechanisms by which HIV-1 may cause neuroinflammation. Chronic expression of pro
      inflammatory cytokines critically contributes to the pathogenesis of HIV
      associated neurological disorders (HANDs), but the host mechanism that regulates
      the HIV-induced cytokine expression in the CNS remains elusive. Here, we present
      evidence for a crucial role of Wnt5a signaling in the expression of pro
      inflammatory cytokines in the spinal cord induced by a major HIV-envelope
      protein, gp120. Wnt5a is mainly expressed in spinal neurons, and rapidly up
      regulated by intrathecal injection (i.t.) of gp120. We show that inhibition of
      Wnt5a by specific antagonists blocks gp120-induced up-regulation of IL-1beta, IL
      6, and TNF-alpha in the spinal cord. Conversely, injection (i.t.) of purified
      recombinant Wnt5a stimulates the expression of these cytokines. To elucidate the
      role of the Wnt5a-regulated signaling pathways in gp120-induced cytokine
      expression, we have focused on CaMKII and JNKs, the well characterized down
      stream targets of Wnt5a signaling. We find that Wnt5a is required for gp120 to
      activate CaMKII and JNK signaling. Furthermore, we demonstrate that the
      Wnt5a/CaMKII pathway is critical for the gp120-induced expression of IL-1beta,
      whereas the Wnt5a/JNK pathway is for TNF-alpha expression. Meanwhile, the
      expression of IL-6 is co-regulated by both pathways. These results collectively
      suggest that Wnt5a signaling cascades play a crucial role in the regulation of
      gp120-induced expression of pro-inflammatory cytokines in the CNS.

PMID- 23539627
TI  - IMP3 protein promotes chemoresistance in breast cancer cells by regulating breast
      cancer resistance protein (ABCG2) expression.
AB  - IMP3, a member of a family of insulin-like growth factor II (IGF-II) mRNA-binding
      proteins (IMPs), is expressed preferentially in triple-negative breast cancers,
      which are resistant to many chemotherapeutics. However, the mechanisms by which
      it impacts breast cancer have not been elucidated. We hypothesized a role for
      IMP3 in chemoresistance based on these observations. Depletion of IMP3 expression
      in triple-negative breast cancer cells increased their sensitivity to doxorubicin
      and mitoxantrone significantly but not to taxol. Given that doxorubicin and
      mitoxantrone are effluxed by breast cancer resistance protein (BCRP), we assessed
      whether IMP3 regulates BCRP. The data obtained demonstrate that IMP3 binds to
      BCRP mRNA and regulates BCRP expression. These findings are significant because
      they provide insight into the mechanism by which IMP3 contributes to aggressive
      cancers, and they highlight the potential for targeting this mRNA-binding protein
      for the clinical management of cancer.

PMID- 23539628
TI  - Elongation factor Ts directly facilitates the formation and disassembly of the
      Escherichia coli elongation factor Tu.GTP.aminoacyl-tRNA ternary complex.
AB  - BACKGROUND: Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex
      with the G-protein elongation factor Tu (EF-Tu) and GTP. RESULTS: EF-Tu.GTP.aa
      tRNA ternary complex formation and decay rates are accelerated in the presence of
      the nucleotide exchange factor elongation factor Ts (EF-Ts). CONCLUSION: EF-Ts
      directly facilitates the formation and disassociation of ternary complex.
      SIGNIFICANCE: This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA
      enters the translating ribosome in a ternary complex with elongation factor Tu
      (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state
      fluorescence methods that enabled us to quantitatively explore the kinetic
      features of Escherichia coli ternary complex formation and decay. The data
      obtained suggest that both processes are controlled by a nucleotide-dependent,
      rate-determining conformational change in EF-Tu. Unexpectedly, we found that this
      conformational change is accelerated by elongation factor Ts (EF-Ts), the
      guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the
      affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non
      hydrolyzable GTP analogs. These results suggest that EF-Ts serves an
      unanticipated role in the cell of actively regulating the abundance and stability
      of ternary complex in a manner that contributes to rapid and faithful protein
      synthesis.

PMID- 23539629
TI  - Death domain-associated protein DAXX promotes ovarian cancer development and
      chemoresistance.
AB  - BACKGROUND: The role of DAXX in ovarian cancer development and metastasis has not
      been investigated before now. RESULTS: Overexpression of DAXX enhanced ovarian
      cancer cell proliferation, colony formation, and migration, whereas Daxx
      depletion had the opposite effects. CONCLUSION: DAXX promotes ovarian cancer cell
      proliferation and chemoresistance. SIGNIFICANCE: ModulatingDAXXmay be an
      effective strategy for preventing the recurrence and chemoresistance of ovarian
      cancers. Understanding the genes involved in apoptosis and DNA damage responses
      may improve therapeutic strategies for ovarian cancer. The death domain
      associated protein DAXX can be either a pro-apoptotic or an anti-apoptotic
      factor, depending on the cell type and context. In this study, we found that DAXX
      was highly expressed in human ovarian surface epithelial tumors but not in
      granulosa cell tumors. In cultured ovarian cancer cells, DAXX interacted with
      promyelocytic leukemia protein (PML) and localized to subnuclear domains (so
      called PML nuclear bodies). A role for DAXX in ovarian cancer cell proliferation,
      metastasis, and radio/chemoresistance was examined. Overexpression of DAXX
      enhanced multiple ovarian cancer cell lines' proliferation, colony formation, and
      migration, whereas Daxx depletion by RNA interference had the opposite effects.
      When transplanted into nude mice, ovarian cancer cells that overexpressed DAXX
      displayed enhanced tumorigenesis capability in vivo, whereas Daxx depletion
      inhibited tumor development. Importantly, Daxx induced tumorigenic transformation
      of normal ovarian surface epithelial cells. Daxx also protected ovarian cancer
      cells against x-irradiation- and chemotherapy-induced DNA damage by interacting
      with PML. Taken together, our results suggest that DAXX is a novel ovarian cancer
      oncogene that promotes ovarian cancer cell proliferation and chemoresistance in
      ovarian cancer cells. Thus, modulating DAXX-PML nuclear body activity may be an
      effective strategy for preventing the recurrence and chemoresistance of ovarian
      cancers.

PMID- 23539631
TI  - Additional issues on screening, prevention, and treatment of abdominal aortic
      aneurysms.
AB  - The prevalence of abdominal aortic aneurysms (AAAs) and AAA-related deaths are
      steadily declining in some countries as a result of the reduction in smoking
      rates. It was thus suggested that screening programs that do not target high-risk
      populations are likely to have very low AAA detection rates. However, this may
      not apply to other countries that do not exhibit similar reductions in smoking
      rates. It was assumed that by using the U.S. Preventive Services Task Force
      screening criteria (men 65-75 years with smoking history) less than 30% of AAAs
      would be captured. A more extensive scoring system that includes additional risk
      factors such as the presence of carotid artery or peripheral arterial disease,
      obesity, hypertension, and so on, may identify almost 90% of AAAs. This article
      discusses this and other issues on screening, prevention, and treatment of AAAs. 

PMID- 23539630
TI  - Cannabinoid receptor 2 suppresses leukocyte inflammatory migration by modulating
      the JNK/c-Jun/Alox5 pathway.
AB  - BACKGROUND: The role of cannabinoid receptor type 2 (Cnr2) in regulating immune
      function had been widely investigated, but the mechanism is not fully understood.
      RESULTS: Cnr2 activation down-regulates 5-lipoxygenase (Alox5) expression by
      suppressing the JNK/c-Jun activation. CONCLUSION: The Cnr2-JNK-Alox5 axis
      modulates leukocyte inflammatory migration. SIGNIFICANCE: Linking two important
      regulators in leukocyte inflammatory migration and providing a potential
      therapeutic strategy for treating human inflammation-associated diseases.
      Inflammatory migration of immune cells is involved in many human diseases.
      Identification of molecular pathways and modulators controlling inflammatory
      migration could lead to therapeutic strategies for treating human inflammation
      associated diseases. The role of cannabinoid receptor type 2 (Cnr2) in regulating
      immune function had been widely investigated, but the mechanism is not fully
      understood. Through a chemical genetic screen using a zebrafish model for
      leukocyte migration, we found that both an agonist of the Cnr2 and inhibitor of
      the 5-lipoxygenase (Alox5, encoded by alox5) inhibit leukocyte migration in
      response to acute injury. These agents have a similar effect on migration of
      human myeloid cells. Consistent with these results, we found that inactivation of
      Cnr2 by zinc finger nuclease-mediated mutagenesis enhances leukocyte migration,
      while inactivation of Alox5 blocks leukocyte migration. Further investigation
      indicates that there is a signaling link between Cnr2 and Alox5 and that alox5 is
      a target of c-Jun. Cnr2 activation down-regulates alox5 expression by suppressing
      the JNK/c-Jun activation. These studies demonstrate that Cnr2, JNK, and Alox5
      constitute a pathway regulating leukocyte migration. The cooperative effect
      between the Cnr2 agonist and Alox5 inhibitor also provides a potential
      therapeutic strategy for treating human inflammation-associated diseases.

PMID- 23539632
TI  - Risk-taking behaviors and subgrouping of college students: a latent class
      analysis.
AB  - Risk-taking behaviors have negative consequences on adolescent and young adult's
      health. The aim of this study was to identify the subgroups of college students
      on the basis of risk-taking behaviors and to assess the role of demographic
      characteristics, religious beliefs, and parental support on membership of
      specific subgroup. The cross-sectional study took place in Tabriz (northwest of
      Iran) in April and May of 2011. The randomly selected sample consisted of 1,837
      college students. A survey questionnaire was used to collect data. Latent class
      analysis was performed to achieve the study's objectives. Four latent classes
      were identified: (a) low risk, (b) cigarette and hookah smoker, (c) sexual and
      drinking risk-takers (for males)/sexual risk takers (for females), and (d) high
      risk. Notably, 13.3% of the males and 4.3% of the females were in the high-risk
      class. The results identified evidence of protective influence of familial
      support and religiosity on risky behaviors. A fair number of college students,
      males in particular, were identified as high risk-takers. Design and
      implementation of preventive interventions for this segment of the population are
      necessary. Higher level of familial support and religiosity may serve as
      preventive factors in risk-taking behaviors. 

PMID- 23539634
TI  - Temperature effects on pitfall catches of epigeal arthropods: a model and method
      for bias correction.
AB  - Carabids and other epigeal arthropods make important contributions to
      biodiversity, food webs and biocontrol of invertebrate pests and weeds. Pitfall
      trapping is widely used for sampling carabid populations, but this technique
      yields biased estimates of abundance ('activity-density') because individual
      activity - which is affected by climatic factors - affects the rate of catch. To
      date, the impact of temperature on pitfall catches, while suspected to be large,
      has not been quantified, and no method is available to account for it. This lack
      of knowledge and the unavailability of a method for bias correction affect the
      confidence that can be placed on results of ecological field studies based on
      pitfall data.Here, we develop a simple model for the effect of temperature,
      assuming a constant proportional change in the rate of catch per  degrees C
      change in temperature, r, consistent with an exponential Q10 response to
      temperature. We fit this model to 38 time series of pitfall catches and
      accompanying temperature records from the literature, using first differences and
      other detrending methods to account for seasonality. We use meta-analysis to
      assess consistency of the estimated parameter r among studies.The mean rate of
      increase in total catch across data sets was 0.0863 +/- 0.0058 per  degrees C of
      maximum temperature and 0.0497 +/- 0.0107 per  degrees C of minimum temperature.
      Multiple regression analyses of 19 data sets showed that temperature is the key
      climatic variable affecting total catch. Relationships between temperature and
      catch were also identified at species level. Correction for temperature bias had
      substantial effects on seasonal trends of carabid catches.Synthesis and
      Applications. The effect of temperature on pitfall catches is shown here to be
      substantial and worthy of consideration when interpreting results of pitfall
      trapping. The exponential model can be used both for effect estimation and for
      bias correction of observed data. Correcting for temperature-related trapping
      bias is straightforward and enables population estimates to be more comparable.
      It may thus improve data interpretation in ecological, conservation and
      monitoring studies, and assist in better management and conservation of habitats
      and ecosystem services. Nevertheless, field ecologists should remain vigilant for
      other sources of bias.

PMID- 23539635
TI  - Novel scenarios of early animal evolution--is it time to rewrite textbooks?
AB  - Understanding how important phenotypic, developmental, and genomic features of
      animals originated and evolved is essential for many fields of biological
      research, but such understanding depends on robust hypotheses about the
      phylogenetic interrelationships of the higher taxa to which the studied species
      belong. Molecular approaches to phylogenetics have proven able to revolutionize
      our knowledge of organismal evolution. However, with respect to the deepest
      splits in the metazoan Tree of Life-the relationships between Bilateria and the
      four non-bilaterian phyla (Porifera, Placozoa, Ctenophora, and Cnidaria)-no
      consensus has been reached yet, since a number of different, often contradictory,
      hypotheses with sometimes spectacular implications have been proposed in recent
      years. Here, we review the recent literature on the topic and contrast it with
      more classical perceptions based on analyses of morphological characters. We
      conclude that the time is not yet ripe to rewrite zoological textbooks and
      advocate a conservative approach when it comes to developing scenarios of the
      early evolution of animals. 

PMID- 23539633
TI  - Endometriosis: hormone regulation and clinical consequences of chemotaxis and
      apoptosis.
AB  - BACKGROUND: The recruitment of immune cells by chemokines and the regulation of
      endometrial cell apoptosis are critical aspects of endometriosis biology. Here,
      we review the local (paracrine) and systemic hormone (endocrine) modulation of
      these two specific, but highly related phenomena. METHODS: We searched Pubmed for
      items published in English between September 1991 and September 2011 and selected
      the studies evaluating the effects of hormones on chemokines or apoptosis in
      normal human endometrium and endometriosis. RESULTS: Estradiol has
      proinflammatory and antiapoptotic effects in endometrial cells, and these effects
      appear to be exacerbated in women with endometriosis. In these women,
      physiological estradiol concentrations are able to induce an enhanced
      inflammatory response mediated by local chemokine production and to reinforce
      mechanisms of cell survival mediated by extracellular signal-regulated kinases
      and Bcl-2. The main effect of progestogens is to inhibit interleukin-8 and other
      chemokines in stromal cells from both eutopic and ectopic endometrium.
      Progesterone is also effective in inducing apoptosis in endometrial and
      endometriotic cells through the inhibition of Bcl-2 and nuclear factor-kappaB.
      CONCLUSIONS: Estrogens and progestogens modulate chemotaxis and apoptosis in
      human endometrium and endometriotic cells and tissues. These endocrine and
      paracrine pathways are perturbed in women with endometriosis, contributing to
      inflammatory responses, abnormal tissue remodeling, therapeutic refractoriness
      and disease persistence. Ultimately, they promote adhesion formation and the
      clinical symptoms of pelvic pain and infertility. A more detailed understanding
      of the molecular mechanisms involved will offer new opportunities for novel
      pharmacological strategies to diagnose and treat endometriosis.

PMID- 23539636
TI  - Ultrasound-assessed non-culprit and culprit coronary vessels differ by age and
      gender.
AB  - AIM: To investigate age- and gender-related differences in non-culprit versus
      culprit coronary vessels assessed with virtual histology intravascular ultrasound
      (VH-IVUS). METHODS: In 390 patients referred for coronary angiography to a single
      center (Luzerner Kantonsspital, Switzerland) between May 2007 and January 2011,
      691 proximal vessel segments in left anterior descending, circumflex and/or right
      coronary arteries were imaged by VH-IVUS. Plaque burden and plaque composition
      (fibrous, fibro-fatty, necrotic core and dense calcium volumes) were analyzed in
      3 age tertiles, according to gender and separated for vessels containing non
      culprit or culprit lesions. To classify as vessel containing a culprit lesion,
      the patient had to present with an acute coronary syndrome, and the VH-IVUS had
      to be performed in a vessel segment containing the culprit lesion according to
      conventional coronary angiography. RESULTS: In non-culprit vessels the plaque
      burden increased significantly with aging (in men from 37% +/- 12% in the lowest
      to 46% +/- 10% in the highest age tertile, P < 0.001; in women from 30% +/- 9% to
      40% +/- 11%, P < 0.001); men had higher plaque burden than women at any age (P <
      0.001 for each of the 3 age tertiles). In culprit vessels of the lowest age
      tertile, plaque burden was significantly higher than that in non-culprit vessels
      (in men 48% +/- 6%, P < 0.001 as compared to non-culprit vessels; in women 44% +/
      18%, P = 0.004 as compared to non-culprit vessels). Plaque burden of culprit
      vessels did not significantly change during aging (plaque burden in men of the
      highest age tertile 51% +/- 9%, P = 0.523 as compared to lowest age tertile; in
      women of the highest age tertile 49% +/- 8%, P = 0.449 as compared to lowest age
      tertile). In men, plaque morphology of culprit vessels became increasingly
      rupture-prone during aging (increasing percentages of necrotic core and dense
      calcium), whereas plaque morphology in non-culprit vessels was less rupture-prone
      and remained constant during aging. In women, necrotic core in non-culprit
      vessels was very low at young age, but increased during aging resulting in a
      plaque morphology that was very similar to men. Plaque morphology in culprit
      vessels of young women and men was similar. CONCLUSION: This study provides
      evidence that age- and gender-related differences in plaque burden and plaque
      composition significantly depend on whether the vessel contained a non-culprit or
      culprit lesion.

PMID- 23539637
TI  - Five-year follow-up of 263 cases of functional bowel disorder.
AB  - AIM: To determine the mortality associated with functional bowel disorders (FBDs)
      and their possible relationship with organic bowel disease. METHODS: Patients who
      satisfied the Rome III criteria for FBD (retrospective diagnosis) were followed
      up by telephone interview and/or outpatient review at 5 years after their first
      attendance. The patients were divided into the following groups: irritable bowel
      syndrome, functional abdominal bloating, functional constipation, functional
      diarrhea and unspecified FBD. The survival of the FBD patients overall and of
      those with each FBD were compared with data obtained from the Guangzhou
      population in 2005. The incidences of colonic cancer overall and for each FBD
      were compared with data from the Chinese population obtained from 56 cancer
      registries in 19 provinces of the country in 2008. RESULTS: Two hundred and sixty
      three patients were followed-up. Five patients died, which was not significantly
      different from the expected survival rate. No differences in mortality among the
      FBDs were found. There were nine cases of organic bowel disease: three colonic
      cancers and six colonic polyps. The incidence of colonic cancer in FBD patients
      was higher than that in the general Chinese population (0.23% vs 0.03%, P <
      0.05). There were significant differences in the incidence of colonic cancer
      among the FBDs (0/134, 0/24, 2/29, 1/66, 0/10, respectively, P < 0.05);
      functional constipation was the most common. The incidence of colonic polyps was
      similar among the FBDs. The baseline age of patients who died was greater than
      that of those who survived (66.60 +/- 6.84 years vs 45.14 +/- 10.34 years, P <
      0.05). The baseline age of patients who had colonic cancer or polyps during
      follow-up was greater than that of those without colonic cancer or polyps (60.33
      +/- 1.53 years vs 45.38 +/- 10.62 years; 54.50 +/- 6.47 years vs 45.34 +/- 10.68
      years, P < 0.05). CONCLUSION: FBDs do not increase the risk of death. The
      incidence of colonic cancer in patients with FBDs may be increased, especially in
      those with functional constipation and in the elderly.

PMID- 23539638
TI  - Primary cerebral lupus as a cause of reversible cognitive impairment.

PMID- 23539639
TI  - Post-traumatic stress disorder symptoms form a traumatic and non-traumatic stress
      response dimension.
AB  - OBJECTIVE: This study aims to determine whether symptoms of post-traumatic stress
      disorder (PTSD) form a latent dimension reflecting responsivity to life events
      and whether PTSD symptoms are specific to traumatic life events. METHOD: A 30
      year longitudinal study of a general population sample of 987 individuals were
      assessed for PTSD symptoms, exposure to adverse life events, and a variety of
      psychosocial measures. PTSD symptoms were tested using a confirmatory factor
      model and a range of fitted models were used to identify significant predictors
      of latent PTSD symptoms. RESULTS: The rate of DSM IV PTSD was 1.9%. However,
      subjects reported high rates of at least one significant traumatic or negative
      life event and PTSD symptoms. The PTSD symptoms conformed well to a single latent
      factor. There were strong linear associations between severity of PTSD symptoms
      and exposure to traumatic and non-traumatic life events. Factors contributing to
      latent PTSD symptoms were gender, childhood anxiety, neuroticism, self-esteem,
      and quality of parental care. CONCLUSION: Criteria for PTSD form an underlying
      dimension reflecting the individual's level of responsivity to traumatic and non
      traumatic stressful life events. PTSD symptoms form a continuum of severity with
      minor stress symptoms at one end and severe PTSD at the other.

PMID- 23539640
TI  - Women need greater safety in psychiatric wards.

PMID- 23539641
TI  - Full central neurokinin-1 receptor blockade is required for efficacy in
      depression: evidence from orvepitant clinical studies.
AB  - Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a
      potential antidepressant mechanism. The selective NK1 antagonist orvepitant
      (GW823296) was used to test this hypothesis. A preliminary positron emission
      tomography study in eight male volunteers drove dose selection for two randomized
      six week studies in patients with major depressive disorder (MDD). Displacement
      of central [(11)C]GR205171 binding indicated that oral orvepitant doses of 30-60
      mg/day provided >99% receptor occupancy for >=24 h. Studies 733 and 833
      randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM
      D)>=22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day
      or placebo (1:1:1). Primary outcome measure was change from baseline in 17-item
      HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study
      733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo
      differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31)
      p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did
      not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI
      (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The
      results support the hypothesis that full, long lasting blockade of central NK1
      receptors may be an efficacious mechanism for the treatment of MDD.

PMID- 23539643
TI  - Response letter regarding the interpretation of gene expression data.
AB  - This is a response letter to Verna E's comments regarding our previous manuscript
      published last year in the World Journal of Gastroenterology entitled
      "Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic
      metastasis in gastric cancer", which evaluated the relationship between these
      expression levels and clinicopathological parameters (Ozmen F et al, World J
      Gastroenterology 2011; 17: 3220-3228). The mean values for lymphatic vessel
      endothelial hyaluronan receptor-1, CD44 and vascular endothelial growth factor
      receptor-3 expression (represented as 2(-DeltaDeltaCt)) were 1.13, 1.24 and 1.17,
      respectively, suggesting an increase in gene expression in tumor tissue compared
      to normal tissue. Despite the increase in gene expression in the cancer tissues
      (2(-DeltaDeltaCt) > 1), only some of the results reached statistical
      significance, which was thoroughly discussed in our paper. In the present letter,
      we report that his comments are flawed and result in confusion. Therefore, we
      herein provide more explanation regarding gene expression in gastric cancer. We
      hope that this letter will address Verna E's misunderstandings.

PMID- 23539644
TI  - Sugars speed up the circle of life.
AB  - By regulating the expression of key microRNA molecules, sugar levels in leaves
      control the transition from the juvenile to the adult form in plants.

PMID- 23539642
TI  - Amphetamine, past and present--a pharmacological and clinical perspective.
AB  - Amphetamine was discovered over 100 years ago. Since then, it has transformed
      from a drug that was freely available without prescription as a panacea for a
      broad range of disorders into a highly restricted Controlled Drug with
      therapeutic applications restricted to attention deficit hyperactivity disorder
      (ADHD) and narcolepsy. This review describes the relationship between chemical
      structure and pharmacology of amphetamine and its congeners. Amphetamine's
      diverse pharmacological actions translate not only into therapeutic efficacy, but
      also into the production of adverse events and liability for recreational abuse.
      Accordingly, the balance of benefit/risk is the key challenge for its clinical
      use. The review charts advances in pharmaceutical development from the
      introduction of once-daily formulations of amphetamine through to
      lisdexamfetamine, which is the first d-amphetamine prodrug approved for the
      management of ADHD in children, adolescents and adults. The unusual metabolic
      route for lisdexamfetamine to deliver d-amphetamine makes an important
      contribution to its pharmacology. How lisdexamfetamine's distinctive
      pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a
      treatment for ADHD and its reduced potential for recreational abuse is also
      discussed.

PMID- 23539645
TI  - Intestinal metaplasia surveillance: searching for the road-map.
AB  - Atrophic gastritis and intestinal metaplasia (IM) of the stomach are common and
      are associated with an increased risk for gastric cancer. In the absence of
      guidelines, a pragmatic management has been performed in Western countries in
      patients with these premalignant conditions. Recently, formal European guidelines
      have been delivered on this topic. Basically, it has been recommended that
      patients with extensive atrophic gastritis (AG) and/or extensive IM should be
      offered endoscopic surveillance every 3 years. On the contrary, no scheduled
      endoscopic/histological control has been advised for those patients with
      precancerous conditions confined to the antrum. In this commentary, we
      highlighted some potential weaknesses in the management formally recommended by
      the new guidelines. In detail, we discussed that AG and IM patients do not share
      the same gastric cancer risk, at least in Western countries, deserving a
      different approach. Some factors significantly associated with gastric cancer
      risk, such as IM type, first-degree family history of gastric cancer, and smoking
      habit have not been considered in tailoring the endoscopic follow-up. Finally,
      some data would suggest that a 3-year follow-up in patients with extensive
      gastric precancerous conditions could result in an inadequate secondary
      prevention.

PMID- 23539646
TI  - Busting myths about UK food production.

PMID- 23539648
TI  - Epidemiology unit recognised as an FAO reference centre.

PMID- 23539649
TI  - Promoting the work of veterinary nurses.

PMID- 23539650
TI  - Canine health awards presented.

PMID- 23539651
TI  - Bovine TB: Welsh farmers reminded of rule changes.

PMID- 23539652
TI  - RCVS decides on new governance arrangements.

PMID- 23539653
TI  - Treating common articular disorders in dogs.

PMID- 23539654
TI  - Canine epilepsy: integrating research in practice.

PMID- 23539655
TI  - Science and practice.

PMID- 23539656
TI  - Skeletal abnormalities in calves.

PMID- 23539657
TI  - Women on RCVS Council.

PMID- 23539658
TI  - Classification of anthelmintics.

PMID- 23539659
TI  - Importance of the time of initiation of mineralocorticoid receptor antagonists on
      risk of mortality in patients with heart failure.
AB  - INTRODUCTION: Several studies have definitively shown the benefit of
      mineralocorticoid receptor antagonists (MRAs) in patients with heart failure
      (HF). However, very few prior studies examined the relationship between the
      timing of initiation of MRAs and prognosis. In addition, on this topic, there is
      no information regarding the specific population of patients suffering a first
      episode of decompensated congestive HF. METHODS: We studied a homogenous cohort
      of patients discharged alive from our hospital after a first episode of
      decompensated congestive HF, in order to clarify the association between time of
      aldosterone receptor antagonist (ARA) initiation (within the first 90 days after
      hospital discharge) and mortality. Our population was composed of a series of
      consecutive patients. All-cause mortality was compared between patients who
      initiated MRAs at discharge (early group) and those who initiated MRAs one month
      later and up to 90 days after discharge (delayed group). We used prescription
      time distribution matching to control for survival difference between groups.
      RESULTS: The early and delayed groups consisted of 365 and 320 patients,
      respectively. During the one-year follow-up, a significant difference in
      mortality was demonstrated between groups. Adjusted hazard ratios (HRs) for early
      versus delayed initiation were 1.72 (95% confidence interval (CI) 0.96 to 2.84)
      at six months, and 1.93 (95% CI 1.18 to 3.14) at one year. CONCLUSIONS: Delay of
      MRA initiation up to 30 to 90 days after discharge implies a significant increase
      in mortality compared with MRA initiation at discharge, after a first episode of
      decompensate congestive HF.

PMID- 23539661
TI  - Relational freedom and therapeutic action.
AB  - Therapeutic action depends on our freedom to allow ourselves novel, unbidden
      experience. How does this novelty arise? What is the process by which some
      portion of the possibilities inherent in any moment's unformulated experience are
      created or selected and emerge in consciousness? And what does it mean to think
      of freedom in this context? What does it mean for the formulation of experience
      to be free? In the frame of reference adopted here, the formulation of experience
      depends on the conscious and unconscious events of the interpersonal field. The
      field facilitates some formulations of experience and prevents others. Thus,
      whatever we can do to make it possible for the analytic relationship to evolve
      freely, without constraint or constriction, is the best way we have to encourage
      the freedom to experience. "Relational freedom" underpins therapeutic action. A
      clinical case is described at length to illustrate these ideas.

PMID- 23539662
TI  - Caravaggio four centuries later: psychoanalytic portraits of ambivalence and
      ambiguity.
AB  - Rome celebrated the four hundredth anniversary of Michelangelo Marisi da
      Caravaggio's death with an historical exhibition of his brief lifetime's work.
      Yet psychoanalysis has not studied this work extensively, despite the artist's
      compelling portrayal of a full range of human affects, including ambivalence.
      Psychoanalysis has studied artistic pioneers such as da Vinci (Freud 1910) and
      Michelangelo (Freud 1914), Giotto's use of blue sky as psychologically innovative
      (Blatt 1994), and Magritte's play with external reality (Spitz 1994). What can we
      learn about Caravaggio's work-including innovative contributions such as visual
      representation of expressed emotions, particularly negative emotions, including
      ambivalence, and remarkably candid, even critical, self-representations-and how
      can this late-sixteenth-century artist teach us about the development of the
      concept of mind underlying psychoanalysis?

PMID- 23539660
TI  - Increased circulatory RAS activity can be inhibited by statins in patients with
      hypercholesterolemia.
AB  - OBJECTIVE: The objective of this paper is to investigate a profile on circulatory
      renin-angiotensin system (RAS) activity in hypercholesterolemic (HC) patients
      treated with statins. METHODS: Eighteen primary HC patients and 18 sex- and age
      matched healthy adults were included in this study as controls. Total cholesterol
      (TC), triglyceride (TG), LDL-C, blood glucose, angiotensin-converting enzyme
      (ACE) activity, and angiotensin II (Ang II) levels were measured before and four
      and eight weeks after beginning statin treatment in the HC group. Similar
      measurements were taken in the control group at baseline. RESULTS: At baseline,
      TC, TG and LDL-C levels, as well as ACE activity and Ang II concentrations, were
      significantly higher in the HC group than in the control group. Based on the
      baseline data collection of 36 participants, there were significant positive
      correlations between ACE activity and TC (r = 0.54) or LDL-C (r = 0.51), and
      between Ang II level and TC (r = 0.34) or LDL-C (r = 0.27). TC, LDL-C, Ang II
      (35.46 +/- 14.49 vs 71.10 +/- 20.47 pg/ml, p < 0.05) levels and ACE activity
      (108.9 +/- 51.9 vs 180.1 +/- 71.3 U/L, p < 0.05) were decreased in HC patients
      eight weeks after starting statin treatment. In HC patients, RAS activity
      correlated positively with TC and LDL-C levels before and after treatment.
      CONCLUSIONS: In HC patients, lowering serum cholesterol with statins is
      associated with decreased circulatory RAS activity.

PMID- 23539663
TI  - Comparison of a quantitative real-time polymerase chain reaction (qPCR) with
      conventional PCR, bacterial culture and ELISA for detection of Mycobacterium
      avium subsp. paratuberculosis infection in sheep showing pathology of Johne's
      disease.
AB  - A quantitative real-time PCR (qPCR) assay employing IS900 gene specific primers
      of Mycobacterium avium subsp. parartuberculosis (MAP) was compared with
      conventional PCR, bacterial culture and enzyme-linked immunosorbent assay in 38
      sheep showing granulomatous enteritis and lymphadenitis with and without
      demonstration of acid-fast bacilli (AFB). The lesions were classified as
      multibacillary (MB) (n = 23), which had diffuse granulomatous lesions with
      abundant AFB, and paucibacillary (PB) (n = 15), which had focal or multifocal
      granulomatous lesions with few or no AFB. In the multibacillary group (MB), IS900
      PCR detected 19 (82.6%), and qPCR detected all 23 (100%) sheep positive for MAP
      in the intestine and lymph node tissues. In the paucibacillary group (PB), IS900
      PCR detected 2 (13.3%), and qPCR detected all 15 (100%) sheep positive for MAP in
      tissues. When results of both groups were taken together, IS900 PCR detected
      21(55.2%), and qPCR detected all 38 (100%) animals positive for MAP genome either
      in the intestine or lymph node tissues. On Herrold egg yolk medium, tissues of 14
      (60.9%) MB and 5 (33.3%) PB sheep were found to be positive for MAP. Out of 27
      sheep (PB = 8, MB = 19) tested by an ELISA, 21 (77.7%) were found to be positive
      for MAP antibody, of which 25% (2/8) and 100% (19/19) sheep were from PB and MB
      sheep, respectively. Based on the results of the present study, it was concluded
      that qPCR was a highly sensitive test in comparison to conventional PCR, ELISA
      and bacterial culture for the diagnosis of paratuberculosis on infected tissues
      especially from paucibacillary sheep. 

PMID- 23539664
TI  - Transcutaneous treatment with vetdrop((r)) sustains the adjacent cartilage in a
      microfracturing joint defect model in sheep.
AB  - The significance of the adjacent cartilage in cartilage defect healing is not yet
      completely understood. Furthermore, it is unknown if the adjacent cartilage can
      somehow be influenced into responding after cartilage damage. The present study
      was undertaken to investigate whether the adjacent cartilage can be better
      sustained after microfracturing in a cartilage defect model in the stifle joint
      of sheep using a transcutaneous treatment concept (Vetdrop((r))). Carprofen and
      chito-oligosaccharids were added either as single components or as a mixture to a
      vehicle suspension consisting of a herbal carrier oil in a water-in-oil phase.
      This mixture was administered onto the skin with the aid of a specific applicator
      during 6 weeks in 28 sheep, allocated into 6 different groups, that underwent
      microfracturing surgery either on the left or the right medial femoral condyle.
      Two groups served as control and were either treated intravenously or sham
      treated with oxygen only. Sheep were sacrificed and their medial condyle
      histologically evaluated qualitatively and semi-quantitatively according to 4
      different scoring systems (Mankin, ICRS, Little and O'Driscoll). The adjacent
      cartilage of animals of group 4 treated transcutaneously with vehicle, chito
      oligosaccharids and carprofen had better histological scores compared to all the
      other groups (Mankin 3.3+/-0.8, ICRS 15.7+/-0.7, Little 9.0+/-1.4). Complete
      defect filling was absent from the transcutaneous treatment groups. The
      experiment suggests that the adjacent cartilage is susceptible to treatment and
      that the combination of vehicle, chitooligosaccharids and carprofen may sustain
      the adjacent cartilage during the recovery period.

PMID- 23539665
TI  - Distribution of Herbal Remedy Knowledge in Tabi, Yucatan, Mexico.
AB  - The distribution of herbal remedy knowledge among a group of people is studied
      for two main reasons: (1) to identify plants that are promising for
      pharmacological analysis, and (2) to examine the factors that lead to herbal
      remedy knowledge erosion as opposed to dynamism in the acquisition of knowledge.
      The goal of this particular study, which is aligned with the second reason, is to
      establish the variation in herbal remedy knowledge among the Yucatec Maya in
      Tabi, Yucatan, Mexico. Free listing and cultural consensus analysis revealed that
      knowledge about a few medicinal plants and herbal remedies was distributed widely
      among the Yucatec Maya in Tabi, whereas the majority of knowledge was
      idiosyncratic. This finding was consistent with other studies of herbal remedy
      knowledge distribution among indigenous groups in Latin America and Africa.
      Assessing patterns in the distribution of herbal remedy knowledge is an important
      next step in determining the degree of dynamism or erosion in knowledge
      acquisition and transmission in Tabi.

PMID- 23539666
TI  - 3.0 T proton magnetic resonance spectroscopy of the liver: quantification of
      choline.
AB  - AIM: To investigate the normal hepatic magnetic resonance spectroscopy findings
      choline/lipid2 (Cho/Lip2) associated with age and body mass index (BMI). METHODS:
      A total of 58 single-voxel proton spectra of the liver were acquired at 3.0 T
      using the eight-channel phased array abdominal coil as the receiver coil.
      Consecutive stacks of breath-hold spectra were acquired using the point resolved
      spectroscopy technique at a short echo time of 30 ms and a repetition time of
      1500 ms. The spectra were processed with the SAGE software package. Areas and
      heights for metabolite resonance were obtained. Student's t test for unpaired
      data was used for comparisons of shimming, Cho/Lip2, and lipid content. RESULTS:
      There were significant negative correlations between the Cho/Lip2 peak height
      ratios and BMI (r = -0.615) and age (r = -0.398) (all P < 0.01). Compared with
      the high-BMI group, the low-BMI group was younger (39.1 +/- 13.0 years vs 47.6 +/
      8.5 years, t = -2.954, P = 0.005); had better water suppression (93.4% +/- 1.4%
      vs 85.6% +/- 11.6%, t = 2.741, P = 0.014); had higher Cho/Lip2 peak heights ratio
      (0.2 +/- 0.14 vs 0.05 +/- 0.04, t = 6.033, P < 0.000); and had lower lipid
      content (0.03 +/- 0.08 vs 0.29 +/- 0.31, t = -3.309, P = 0.004). Compared with
      the older group, the younger group had better shimming effects (17.1 +/- 3.6 Hz
      vs 22.0 +/- 6.8 Hz, t = -2.919, P = 0.008); higher Cho/Lip2 peak heights ratios
      (0.03 +/- 0.05 vs 0.09 +/- 0.12, t = 2.4, P = 0.020); and lower lipid content
      (0.05 +/- 0.11 vs 0.23 +/- 0.32, t = -2.337, P = 0.031). Compared with the low
      choline peak group, the high-choline peak group had lower lipid content (0.005 +/
      0.002 vs 0.13 +/- 0.23, t = -3.796, P < 0.000); lower BMI (19.6 +/- 2.4 vs 23.9
      +/- 3.0, t = -4.410, P < 0.000); and younger age (34.7 +/- 10.0 years vs 43.2 +/-
      12.5 years, t = -2.088, P = 0.041). CONCLUSION: Lipid accumulation could result
      from the increased fat in the body depending on age and BMI. Lipid can mask the
      resonance signal of choline.

PMID- 23539667
TI  - The effects of high-intensity intermittent exercise compared with continuous
      exercise on voluntary water ingestion.
AB  - Water intake occurs following a period of high-intensity intermittent exercise
      (HIIE) due to sensations of thirst yet this does not always appear to be caused
      by body water losses. Thu.s, the aim was to assess voluntary water intake
      following HIIE. Ten healthy males (22 +/- 2 y, 75.6 +/- 6.9 kg, VO2(peak) 57.3 +/
      11.4 m . kg(-1) . min(-1); mean +/- SD) completed two trials (7-14 d apart).
      Subjects sat for 30 min then completed an exercise period involving 2 min of rest
      followed by 1 min at 100% VO2(peak repeated for 60 min (HIIE) or 60 min
      continuously at 33% VO2(peak) (LO). Subjects then sat for 60 min and were allowed
      ad libitum water intake. Body )mass was measured at start and end of trials.
      Serum osmolality, blood lactate, and sodium concentrations, sensations of thirst
      and mouth dryness were measured at baseline, postexercise and after 5, 15, 30,
      and 60 min of recovery. Vasopressin concentration was measured at baseline,
      postexercise, 5 min, and 30 min. Body mass loss over the whole trial was similar
      (HIIE: 0.77 +/- 0.50; LO: 0.85 +/- 0.55%; p = .124). Sweat lost during exercise
      (0.78 +/- 0.22 vs. 0.66 +/- 0.26 L) and voluntary water intake during recovery
      (0.416 +/- 0.299 vs. 0.294 +/- 0.295 L; p < .05) were greater in HIIE. Serum
      osmolality (297 +/- 3 vs. 288 +/- 4 mOsmol . kg(-1)), blood lactate (8.5 +/- 2.7
      vs. 0.7 +/- 0.4 mmol . L(-1)), serum sodium (146 +/- 1 vs. 143 +/- 1 mmol . L(
      1)) and vasopressin (9.91 +/- 3.36 vs. 4.43 +/- 0.86 pg . ml(-1)) concentrations
      were higher after HIIE (p < .05) and thirst (84 +/- 7 vs. 60 +/- 21) and mouth
      dryness (87 +/- 7 vs. 64 +/- 23) also tended to be higher (p = .060). Greater
      voluntary water intake after HIIE was mainly caused by increased sweat loss and
      the consequences of increased serum osmolality mainly resulting from higher blood
      lactate concentrations.

PMID- 23539668
TI  - Distribution of power output when establishing a breakaway in cycling.
AB  - A number of laboratory-based performance tests have been designed to mimic the
      dynamic and stochastic nature of road cycling. However, the distribution of power
      output and thus physical demands of high-intensity surges performed to establish
      a breakaway during actual competitive road cycling are unclear. Review of data
      from professional road-cycling events has indicated that numerous short-duration
      (5-15 s), high-intensity (~9.5-14 W/kg) surges are typically observed in the 5-10
      min before athletes' establishing a breakaway (ie, riding away from a group of
      cyclists). After this initial high-intensity effort, power output declined but
      remained high (~450-500 W) for a further 30 s to 5 min, depending on race
      dynamics (ie, the response of the chase group). Due to the significant influence
      competitors have on pacing strategies, it is difficult for laboratory-based
      performance tests to precisely replicate this aspect of mass-start competitive
      road cycling. Further research examining the distribution of power output during
      competitive road racing is needed to refine laboratory-based simulated stochastic
      performance trials and better understand the factors important to the success of
      a breakaway. 

PMID- 23539669
TI  - Influence of D,L-sotalol on baroreflex sensitivity response to posture following
      coronary artery bypass graft surgery in men and women.
AB  - Low baroreflex sensitivity (BRS) following coronary artery bypass graft (CABG)
      surgery increases the risk of sympathetically mediated cardiac arrhythmias. To
      reduce this risk, D,L-sotalol, a nonselective beta-adrenergic receptor antagonist
      (Class II) and an antiarrhythmic (Class III), is prescribed postoperatively.
      However, its effect on BRS has not been reported. The purpose of this study was
      to characterize the influence of D,L-sotalol on BRS measures in supine and
      standing postures 4 days following CABG surgery. BRS was measured in 27 men and
      10 women receiving D,L-sotalol and compared with archival data for 21 men and 10
      women obtained prior to the routine administration of D,L-sotalol. In the latter
      (control) group, 61% had BRS of less than 3 ms/mmHg in the supine posture and 74%
      in the standing posture compared to 42% with less than 3 ms/mmHg in the supine
      posture and 65% in the standing posture in the D,L-sotalol group. Men in the D,L
      sotalol group showed higher R-R interval and BRS in both supine and standing
      postures compared with controls. Women in the D,L-sotalol group had higher R-R
      interval in the supine posture. The higher BRS in men not only reduces the risk
      of arrhythmias after CABG surgery but may also allow a more rapid circulatory
      response to the standing posture, thereby decreasing the risk of syncope.

PMID- 23539670
TI  - A pilot study evaluating daily physical activity before and after cardiac
      resynchronization therapy.
AB  - Benefits of daily physical activity are well known, but there are limited data to
      describe physical activity in heart failure patients who receive cardiac
      resynchronization therapy devices. The purpose of this pilot study was to
      evaluate changes in physical activity (PA) levels before and 3 months after
      Cardiac Resynchronization Therapy (CRT) and determine relationships of PA to
      physical function and comorbidities, as well as describe changes in heart failure
      symptoms. This was a prospective pre-/post- design that included a convenience
      sample of 21 subjects using self- report questionnaires and 6-minute walk test
      (6MWT). In this sample, there was a 2.6 hour increase in high level PA (p =
      0.024). 6MW distance improved 27% (p < .0001). Subjects experienced a 25%
      reduction in dyspnea (p = 0.015). Knowledge gained from this study adds to the
      understanding of the patient response to CRT. Further study is recommended to
      generalize findings and explore whether an intervention (cardiac rehabilitation)
      is indicated. 

PMID- 23539671
TI  - Choice of drugs in the treatment of chronic hepatitis B in pregnancy.
AB  - The selection of antiviral drugs for chronic hepatitis B (CHB) treatment in
      pregnancy is very difficult since none of the drugs have been approved for use in
      pregnancy. Transmission from mother to newborn remains the most frequent route of
      infection in mothers with high viral load and positive hepatitis B e antigen
      status, even with the use of appropriate prophylaxis with hepatitis B virus (HBV)
      immunoglobulin and HBV vaccination. We read from the article written by Yi et al
      that lamivudine treatment in early pregnancy was safe and effective. However, we
      could not understand why adefovir dipivoxil (ADV) was used in three pregnancy
      cases, since ADV has been classified as pregnancy category C. In pregnancy,
      telbivudine or tenofovir should be selected when the treatment of CHB is
      necessary, since these drugs have been classified as Food and Drug Administration
      pregnancy risk category B.

PMID- 23539672
TI  - Determinants of angiographic thrombus burden in patients with ST-segment
      elevation myocardial infarction.
AB  - AIMS: We aimed to investigate the determinants of angiographic thrombus burden in
      patients with ST-segment elevation myocardial infarction (STEMI) who underwent
      primary percutaneous coronary intervention (pPCI). METHODS: The study population
      consisted of 662 patients with nonanemic STEMI who underwent pPCI. Clinical,
      laboratory, and demographic properties of the patients were recorded. Baseline
      hematologic indices were measured at the time of admission. Angiographic coronary
      thrombus burden was scored based on thrombolysis in myocardial infarction (TIMI)
      thrombus grades. After wiring and/or small balloon dilation, patients with
      thrombus burden grades 4 and 5 were defined as high thrombus burden, and patients
      with thrombus burden <grade 4 was defined as low thrombus burden. RESULT:
      Patients with high thrombus burden had more family history of coronary artery
      disease, longer pain to balloon time, higher Killip class (>=II), higher
      neutrophil to lymphocyte ratio, red cell distribution width (RDW), baseline
      creatine kinase-MB fraction (CK-MB) and baseline troponin, higher peak CK-MB, and
      peak troponinbut lower triglycerides. Angiographically, patients with high
      thrombus burden had longer lesion in the infarct-related artery, less frequent
      direct stenting, lower epicardial and myocardial perfusion, more frequent distal
      embolization, and more frequent electrocardiographic and angiographic no reflow.
      In multivariate logistic regression analysis, only RDW (odds ratio: 1.29, 95%
      confidence interval 1.19-1.39, P < .001) was determined as independent predictor.
      The area under the receiver-operating characteristic curve of the RDW was 0.733
      (0.690-0.776, P < .001) to predict high TIMI thrombus burden. CONCLUSION: Present
      study results demonstrated that high thrombus burden in patients with STEMI was
      associated with impaired postprocedural epicardial and myocardial perfusion and
      higher no reflow and distal embolization; and increased RDW values were
      independent predictors of coronary thrombus burden.

PMID- 23539673
TI  - The effects of eosinophil on the left atrial thrombus in patients with atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disorder.
      Atrial fibrillation causes a 5-fold increased risk for thromboembolic stroke. It
      is known that eosinophils play an important role in thrombosis. We aimed to
      compare the number of eosinophil counts of the patients with and without thrombi
      in the left atrium (LA) or in the left atrial appendage (LAA) and to ascertain
      the association of eosinophil counts with the presence of thrombi. METHOD: The
      study included 89 patients diagnosed with persistent AF who underwent
      transesophageal echocardiography and designated to undergo cardioversion. The
      patients were divided into 2 groups: group 1 consisted of 40 patients (18 male;
      average age 63.27 +/- 1.4) who had thrombus formation in the LA or LAA, and group
      2 consisted of 49 patients (23 male; average age 66.53 +/- 1.56) who did not have
      any thrombus in the LA or LAA. These patients underwent concurrent routine
      biochemical tests and eosinophil count on whole blood count was also performed.
      RESULTS: Baseline characteristics of the study groups were comparable. Group 1
      patients had higher eosinophil and mean platelet volume values than group 2
      (233.0 +/- 30.7 vs 118.9 +/- 11.8 and 9.77 +/- 0.20 vs 8.27 +/- 0.12 fL, P <
      .001, respectively). In group 1, the patients' LA diameter is higher than that in
      group II. CONCLUSION: As a result, our study revealed a relationship between
      eosinophil count and LA thrombus in patients with nonvalvular AF.

PMID- 23539675
TI  - Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells
      in the Sheep Heart.
AB  - BACKGROUND: Laboratory large animal models are important for establishing the
      efficacy of stem cell therapies that may be translated into clinical use. The
      similarity of ovine and human cardiovascular systems provides an opportunity to
      use the sheep as a large animal model in which to optimize cell-based treatments
      for the heart. Recent clinical trials in humans using endogenous cardiovascular
      progenitor cells report significant improvement in cardiac function following
      stem cell-based therapy. To date, however, endogenous cardiovascular progenitor
      cells have not been isolated from the sheep heart. METHODS: Cardiovascular cells
      expressing SSEA-4, CD105 and c-kit were isolated by flow cytometry and cloned
      from the right atrium of neonatal sheep. The expression of GATA-4, c-kit, and
      Isl1 was identified by PCR in the cloned cells. Immunohistochemical staining was
      used to compare the number of SSEA-4 positive cells in the right auricle, right
      atrium, left ventricle and the apex of the heart of fetal, neonatal and adult
      sheep. The number of SSEA4+cells was also compared in fetal, pregnant and non
      pregnant adult sheep. RESULTS: Four distinct cardiac progenitor cell sub
      populations were identified in sheep, including CD105+SSEA-4+c-kit+Isl1+GATA
      4+cells, CD105+SSEA-4+c-kit+Isl1+GATA-4-cells, CD105+SSEA-4-c-kit-Isl1+GATA-4
      cells, and CD105+SSEA-4-c-kit+Isl1+GATA-4-cells. Immunohistochemical staining for
      SSEA-4 showed that labeled cells were most abundant in the right atrium of fetal
      hearts where niches of progenitor cells could be identified. CONCLUSION: We
      determined the phenotype and distribution of cardiac progenitor cells in the
      sheep heart. The availability of cloned endogenous cardiac progenitor cells from
      sheep will provide a valuable resource for optimizing the conditions for cardiac
      repair in the ovine model.

PMID- 23539674
TI  - Actual concept of "probiotics": is it more functional to science or business?
AB  - It is our contention that the concept of a probiotic as a living bacterium
      providing unspecified health benefits is inhibiting the development and
      establishment of an evidence base for the growing field of pharmacobiotics. We
      believe this is due in part to the current regulatory framework, lack of a clear
      definition of a probiotic, the ease with which currently defined probiotics can
      be positioned in the market place, and the enormous profits earned for minimum
      investment in research. To avoid this, we believe the following two actions are
      mandatory: international guidelines by a forum of stakeholders made available to
      scientists and clinicians, patient organizations, and governments; public
      research funds made available to the scientific community for performing
      independent rigorous studies both at the preclinical and clinical levels.

PMID- 23539676
TI  - State of the Art Review: Colorectal Cancer Screening.
AB  - Although colorectal cancer is the third leading cause of cancer-related deaths in
      the U.S., the burden of this disease could be dramatically reduced by increased
      utilization of screening. Evidence-based recommendations and guidelines from
      national societies recommend screening all average risk adults starting at age
      fifty. However, the myriad of screening options and slight differences in
      screening recommendations between guidelines may lead to confusion among patients
      and their primary care providers. This goal of this review is to briefly
      summarize the colorectal cancer screening guidelines issued by three major
      organizations, compare their recommendations, and address emerging issues in
      colorectal cancer screening.

PMID- 23539677
TI  - Chronic mesenteric ischemia: time to remember open revascularization.
AB  - Chronic mesenteric ischemia is caused by stenosis or occlusion of one or more
      visceral arteries. It represents a therapeutic challenge and diagnosis and
      treatment require close interdisciplinary cooperation between gastroenterologist,
      vascular surgeon and radiologist. Although endovascular treatment modalities have
      been developed, the number of restenoses ultimately resulting in treatment
      failure is high. In patients fit for open surgery, the visceral arteries should
      be revascularized conventionally. These patients will then experience long term
      relief from the symptoms, a better quality of life and a better overall survival.

PMID- 23539680
TI  - Accounting for kids in accountable care: a policy perspective.

PMID- 23539678
TI  - Upper gastrointestinal microbiota and digestive diseases.
AB  - Metagenomics which combines the power of genomics, bioinformatics, and systems
      biology, provide new access to the microbial world. Metagenomics permit the
      genetic analysis of complex microbial populations without requiring prior
      cultivation. Through the conceptual innovations in metagenomics and the
      improvements in DNA high-throughput sequencing and bioinformatics analysis
      technology, gastrointestinal microbiology has entered the metagenomics era and
      become a hot topic worldwide. Human microbiome research is underway, however,
      most studies in this area have focused on the composition and function of the
      intestinal microbiota and the relationship between intestinal microbiota and
      metabolic diseases (obesity, diabetes, metabolic syndrome, etc.) and intestinal
      disorders [inflammatory bowel disease, colorectal cancer, irritable bowel
      syndrome (IBS), etc.]. Few investigations on microbiota have been conducted
      within the upper gastrointestinal tract (esophagus, stomach and duodenum). The
      upper gastrointestinal microbiota is essential for several gastrointestinal
      illnesses, including esophagitis, Barrett's esophagus, and esophageal carcinoma,
      gastritis and gastric cancer, small intestinal bacterial overgrowth, IBS and
      celiac disease. However, the constitution and diversity of the microbiota in
      different sections of the upper gastrointestinal tract under health and various
      disease states, as well as the function of microbiota in the pathogenesis of
      various digestive diseases are still undefined. The current article provides an
      overview of the recent findings regarding the relationship between upper
      gastrointestinal microbiota and gastrointestinal diseases; and discusses the
      study limitations and future directions of upper gastrointestinal microbiota
      research.

PMID- 23539679
TI  - Scolopendra subspinipes mutilans protected the cerulein-induced acute
      pancreatitis by inhibiting high-mobility group box protein-1.
AB  - AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM)
      on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: SSM water
      extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to
      the first injection of cerulein. Once AP developed, the stable cholecystokinin
      analogue, cerulein was injected hourly, over a 6 h period. Blood samples were
      taken 6 h later to determine serum amylase, lipase, and cytokine levels. The
      pancreas and lungs were rapidly removed for morphological examination,
      myeloperoxidase assay, and real-time reverse transcription polymerase chain
      reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells
      were isolated using collagenase method. Then the cells were pre-treated with SSM,
      then stimulated with cerulein. The cell viability, cytokine productions and high
      mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating
      mechanisms of SSM action were evaluated. RESULTS: The administration of SSM
      significantly attenuated the severity of pancreatitis and pancreatitis associated
      lung injury, as was shown by the reduction in pancreatic edema, neutrophil
      infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic
      weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA
      expression of multiple inflammatory mediators such as tumor necrosis factor-alpha
      and interleukin-1beta. In addition, treatment with SSM inhibited HMGB-1
      expression in the pancreas during AP. In accordance with in vivo data, SSM
      inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release.
      SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear
      factor (NF)-kappaB. CONCLUSION: These results suggest that SSM plays a protective
      role during the development of AP and pancreatitis associated lung injury via
      deactivating c-Jun NH2-terminal kinase, p38 and NF-kappaB.

PMID- 23539681
TI  - Chronic otitis media in children: an evidence-based guide for diagnosis and
      management.
AB  - AIM: To provide an easy-to-follow evidence-based diagnostic and therapeutic
      algorithm for the management of chronic otitis media (COM) in children.
      MATERIALS/METHODS: Literature review and critical analysis of the available
      evidence in Medline and other scientific database sources. DATA SYNTHESIS:
      Otorrhea and hearing loss are the cardinal symptoms of COM, while oto-microscopy
      and imaging techniques can confirm the diagnosis. Conservative treatment is
      acceptable to some extent (i.e. mild cases of COM without cholesteatoma). It
      involves topical drops (quinolones as first choice drugs- strength of
      recommendation B), as well as performing aural toilet (strength of recommendation
      B), and avoiding water ingress. Tympanoplasty without mastoidectomy is expected
      to improve hearing in cases of non-cholesteatomatous COM (strength of
      recommendation C), and positively affect the children's quality of life (strength
      of recommendation B). Less experienced surgeons and inflamed, wet middle ear
      mucosa represent the two most important factors, which could lead to
      reperforations (strength of recommendation C). The surgical management of COM
      with cholesteatoma tends to employ the least invasive surgical technique, in
      order to obtain a small self-cleaning mastoid cavity, as well as good hearing
      results (strength of recommendation C). CONCLUSION: The treatment of choice in
      most cases of pediatric COM is surgery. Figure 1 proposes a detailed and easy-to
      follow evidence-based algorithm with regard to the diagnosis and management of
      COM in children.

PMID- 23539682
TI  - Parent perspectives on attrition from tertiary care pediatric weight management
      programs.
AB  - OBJECTIVE: To describe parent/caregiver reasons for attrition from tertiary care
      weight management clinics/programs. STUDY DESIGN: A telephone survey was
      administered to 147 parents from weight management clinics/programs in the
      National Association of Children's Hospitals and Related Institutions' (now
      Children's Hospital Association's) FOCUS on a Fitter Future II collaborative.
      RESULTS: Scheduling, barriers to recommendation implementation, and
      transportation issues were endorsed by more than half of parents as having a
      moderate to high influence on their decision not to return. Family motivation and
      mismatched expectations between families and clinic/program staff were mentioned
      as influential by more than one-third. Only mismatched expectations correlated
      with patient demographics and program characteristics. [corrected]. CONCLUSIONS:
      Although limited by small sample size, the study found that parents who left
      geographically diverse weight management clinics/programs reported similar
      reasons for attrition. Future efforts should include offering alternative visit
      times, more treatment options, and financial and transportation assistance and
      exploring family expectations.

PMID- 23539683
TI  - A study regarding Spanish-speaking parents' preference of physician attire in the
      pediatric emergency room.
AB  - OBJECTIVE: A study to determine Spanish-speaking parents' acceptance of the
      physician's attire in the pediatric emergency department. HYPOTHESIS: The attire
      of the physicians does not matter for the parents. METHODS AND MATERIALS: The
      sample size was 450. An anonymous patient survey with no identifiers was used.
      The sample questionnaire was enclosed, and the parents were asked to answer the
      questionnaire. The results were interesting; patients preferred physicians who
      wear hospital scrubs (410/450 or 91%) and short hair (430/450 = 96%). They
      preferred physicians wearing sneakers (430/450 = 96%) compared with dress shoes,
      and male physicians with moustaches/beards and wearing glasses (450/450 = 100%).
      Parents did not like women physicians wearing makeup and high heels. CONCLUSIONS:
      Parents prefer physicians wearing hospital scrubs and sneakers and having short
      hair. This could indicate that parents do not prefer formal attire in the
      pediatric emergency room (ER). Also, a gender difference was noticed. Parents do
      not prefer women physicians with high heels and make up. But, they tolerate male
      physicians with moustaches/beards. This could be related to the fact that most of
      the parent questionnaires were answered by Spanish women. Results are interesting
      and useful in addressing the question of physicians' attire in the pediatric ER
      in the context of a predominantly Spanish speaking population.

PMID- 23539684
TI  - Disaster preparedness for technology and electricity-dependent children and youth
      with special health care needs.
AB  - BACKGROUND: Children and youth with special health care needs (CYSHCN) are
      complex and often dependent on electrical devices (technoelectric dependent) for
      life support/maintenance. Because they are reliant on electricity and electricity
      failure is common, the purpose of this study was to survey their preparedness for
      electricity failure. METHODS: Parents and caregivers of technoelectric CYSHCN
      were asked to complete a preparedness questionnaire. We collected a convenience
      sample of 50 patients. RESULTS: These 50 patients utilized a total of 166
      electrical devices. A home ventilator, oxygen concentrator, and a feeding pump
      were identified as the most important device for the children in 35 of the 50
      patients, yet only 19 of the 35 patients could confirm that this device had a
      battery backup. Also, 22 of the 50 patients had a prolonged power failure
      preparedness plan. CONCLUSION: Technoelectric-dependent CYSHCN are poorly
      prepared for electrical power failure.

PMID- 23539685
TI  - Usefulness of urinary immune biomarkers in the evaluation of neonatal sepsis: a
      pilot project.
AB  - OBJECTIVE: Our hypothesis is that specific proinflammatory and anti-inflammatory
      urinary cytokines are useful in the diagnostic evaluation of risk for sepsis in
      term neonates. We conducted a pilot, prospective hospital-based longitudinal
      observational study to test the urine of term neonates with a 13 biomarker panel
      of cytokines. METHODS: Infants were divided into 2 groups: The control group (n =
      15) consisted of infants admitted to newborn nursery, and the test group (n = 15)
      consisted of infants admitted to the neonatal intensive care unit for presumed
      sepsis. Bagged urine samples were collected from 30 term neonates for testing our
      hypothesis. RESULTS: Urinary interleukin (IL)-8 (P = .004*), inducible protein
      (IP)-10 (P = .007*), and monocyte chemoattractant protein (MCP)-1 (P = .02) were
      significantly increased in the test group compared with the control group.
      CONCLUSIONS: Urinary IL-8, IP-10, and MCP-1 are proinflammatory cytokines that
      are increased in the neonate during an infectious inflammatory process. These may
      be useful predictors as an adjunct to the current protocols to recognize neonatal
      sepsis.

PMID- 23539686
TI  - A pilot study: does obesity begin in the first year of life?
AB  - AIM: To determine if growth patterns in healthy infants can identify associations
      with obesity at age 5 years. METHOD: Body mass index growth patterns from birth
      to 1 year were described for cohorts of children who were classified at 5 years
      as normal weight (n = 61), overweight (n = 47), obese (n = 41), and morbidly
      obese (n = 72). A longitudinal analysis of body mass index means based on the age
      postbirth was conducted and graphed. RESULTS: Distinctions in growth patterns
      were evident before 1 year postbirth. Children who were normal weight at 5 years
      demonstrated a growth pattern in the first year that differed from children who
      were overweight, obese, or morbidly obese at 5 years. CONCLUSIONS: Obesity growth
      patterns were seen in infancy and are clinically important because identification
      of infants who do not fit a normal weight pattern can occur and thus guide
      individualized interventions in the first year postbirth while precursors of
      later health are still forming.

PMID- 23539687
TI  - Awareness is not enough: the need to increase meningococcal vaccine uptake.
AB  - OBJECTIVE: Adolescent meningococcal vaccine uptake remains low. We examined
      vaccine awareness among parents of adolescents and uptake. METHODS: Parents of
      adolescents aged 11 to 17 years (n = 1281) participated in a statewide survey.
      Logistic regression with weighted data provided population-based estimates.
      RESULTS: In all, 65% had heard of meningococcal vaccine; parents more likely to
      report awareness had adolescents aged 16 to 17 years, in private school, or with
      health insurance. In total, 44% of aware parents reported vaccination; vaccinated
      teens were more likely to be black (odds ratio [OR] = 2.17), had a preventive
      checkup within 12 months (OR = 3.03), or resided with another child <=18 years
      (OR = 1.83). Many parents of unvaccinated adolescents (38.5%) did not plan to
      vaccinate them within 12 months. The most common reasons for not vaccinating were
      providers not recommending it and believing adolescents did not need it.
      CONCLUSION: Many parents aware of meningococcal vaccine did not vaccinate their
      adolescents. Interventions that include increasing provider recommendation and
      annual visits may increase uptake.

PMID- 23539688
TI  - Neck abscess due to goose feathers leaked from a down comforter: case report,
      review of literature, and recommendations for parents.
AB  - We present a 10-month-old baby girl who developed a neck abscess from the
      penetration of neck skin by 2 goose feathers that leaked from a down comforter.
      We review the risks of down and feather bedding and discuss consumer
      recommendations for parents and pediatricians. 

PMID- 23539689
TI  - Cold preparation use in young children after FDA warnings: do concerns still
      exist?
AB  - OBJECTIVE: To characterize the use and delivery of cough and cold medicines in
      children younger than 6 presenting to an inner-city pediatric emergency
      department (PED) following 2007 FDA warnings. METHODS: A cross-sectional
      observational study was performed using a convenience sampling of PED patients
      during the fall of 2010. Caregivers were presented with 6 commonly used cough
      medicine preparations and were asked to demonstrate if and how they would
      administer these to their children. RESULTS: In all, 65 patients and their
      caregivers consented and participated in the study. During the demonstration, 82%
      (53/65) stated that they would treat with cough or cold medicines, and 72%
      (38/53) incorrectly dosed the medication they desired to give. CONCLUSIONS:
      Despite current recommendations, cough and cold medicines are still used in
      children younger than 6 years of age. A significant portion of caregivers report
      that they are still unaware of public warnings, potential side effects, and
      interactions with other medications.

PMID- 23539691
TI  - Reshaping orthopaedic history.

PMID- 23539690
TI  - Improving pediatrician knowledge about environmental triggers of asthma.
AB  - BACKGROUND: Control of environmental triggers (ETs) greatly improves asthma
      outcomes in children. Disseminating these findings to general pediatricians has
      not been well established. METHODS: After delivering a structured and
      standardized presentation on ET identification and control to pediatricians, we
      surveyed them about knowledge and practices of ET assessment and management. We
      analyzed matched responses for pre/post and 3- to 6-month follow-up using
      McNemar's chi(2) test. RESULTS: Matched data were available for 367 participants,
      and 3- to 6-month follow-up data were available for 83. There was a significant
      posttraining increase in intention to ask about ETs and recommend ET management.
      After 3 to 6 months, all responses remained significantly higher than baseline,
      except "likely to refer to an asthma specialist." CONCLUSION: Pediatricians
      reported a significant improvement in knowledge about ETs of asthma and a
      willingness to incorporate exposure history questions and remediation
      recommendations in their routine practice.

PMID- 23539692
TI  - Wrong site surgery: The maze of potential errors.

PMID- 23539693
TI  - Lateral compartment osteoarthritis of the knee: Biomechanics and surgical
      management of end-stage disease.
AB  - The lateral compartment is predominantly affected in approximately 10% of
      patients with osteoarthritis of the knee. The anatomy, kinematics and loading
      during movement differ considerably between medial and lateral compartments of
      the knee. This in the main explains the relative protection of the lateral
      compartment compared with the medial compartment in the development of
      osteoarthritis. The aetiology of lateral compartment osteoarthritis can be
      idiopathic, usually affecting the femur, or secondary to trauma commonly
      affecting the tibia. Surgical management of lateral compartment osteoarthritis
      can include osteotomy, unicompartmental knee replacement and total knee
      replacement. This review discusses the biomechanics, pathogenesis and development
      of lateral compartment osteoarthritis and its management.

PMID- 23539694
TI  - Surgical treatment of femoroacetabular impingement in patients with slipped
      capital femoral epiphysis: A review of current surgical techniques.
AB  - Slipped capital femoral epiphysis (SCFE) is relatively common in adolescents and
      results in a complex deformity of the hip that can lead to femoroacetabular
      impingement (FAI). FAI may be symptomatic and lead to the premature development
      of osteoarthritis (OA) of the hip. Current techniques for managing the deformity
      include arthroscopic femoral neck osteochondroplasty, an arthroscopically
      assisted limited anterior approach to the hip, surgical dislocation, and proximal
      femoral osteotomy. Although not a routine procedure to treat FAI secondary to
      SCFE deformity, peri-acetabular osteotomy has been successfully used to treat FAI
      caused by acetabular over-coverage. These procedures should be considered for
      patients with symptoms due to a deformity of the hip secondary to SCFE.

PMID- 23539695
TI  - Radiological findings that may indicate a prior silent slipped capital femoral
      epiphysis in a cohort of 2072 young adults.
AB  - The reported prevalence of an asymptomatic slip of the contralateral hip in
      patients operated on for unilateral slipped capital femoral epiphysis (SCFE) is
      as high as 40%. Based on a population-based cohort of 2072 healthy adolescents
      (58% women) we report on radiological and clinical findings suggestive of a
      possible previous SCFE. Common threshold values for Southwick's lateral head
      shaft angle (>= 13 degrees ) and Murray's tilt index (>= 1.35) were used. New
      reference intervals for these measurements at skeletal maturity are also
      presented. At follow-up the mean age of the patients was 18.6 years (17.2 to
      20.1). All answered two questionnaires, had a clinical examination and two hip
      radiographs. There was an association between a high head-shaft angle and
      clinical findings associated with SCFE, such as reduced internal rotation and
      increased external rotation. Also, 6.6% of the cohort had Southwick's lateral
      head-shaft angle >= 13 degrees , suggestive of a possible slip. Murray's tilt
      index >= 1.35 was demonstrated in 13.1% of the cohort, predominantly in men, in
      whom this finding was associated with other radiological findings such as pistol
      grip deformity or focal prominence of the femoral neck, but no clinical findings
      suggestive of SCFE. This study indicates that 6.6% of young adults have
      radiological findings consistent with a prior SCFE, which seems to be more common
      than previously reported.

PMID- 23539696
TI  - Extended venous thromboembolism prophylaxis in patients undergoing hip fracture
      surgery - the SAVE-HIP3 study.
AB  - There is currently limited information available on the benefits and risks of
      extended thromboprophylaxis after hip fracture surgery. SAVE-HIP3 was a
      randomised, double-blind study conducted to evaluate the efficacy and safety of
      extended thromboprophylaxis with the ultra-low molecular-weight heparin
      semuloparin compared with placebo in patients undergoing hip fracture surgery.
      After a seven- to ten-day open-label run-in phase with semuloparin (20 mg once
      daily subcutaneously, initiated post-operatively), patients were randomised to
      once-daily semuloparin (20 mg subcutaneously) or placebo for 19 to 23 additional
      days. The primary efficacy endpoint was a composite of any venous thromboembolism
      (VTE; any deep-vein thrombosis and non-fatal pulmonary embolism) or all-cause
      death until day 24 of the double-blind period. Safety parameters included major
      and clinically relevant non-major bleeding, laboratory data, and treatment
      emergent adverse events (TEAEs). Extended thromboprophylaxis with semuloparin
      demonstrated a relative risk reduction of 79% in the rate of any VTE or all-cause
      death compared with placebo (3.9% vs 18.6%, respectively; odds ratio 0.18 (95%
      confidence interval 0.07 to 0.45), p < 0.001). Two patients in the semuloparin
      group and none in the placebo group experienced clinically relevant bleeding.
      TEAE rates were similar in both groups. In conclusion, the SAVE-HIP3 study
      results demonstrate that patients undergoing hip fracture surgery benefit from
      extended thromboprophylaxis.

PMID- 23539697
TI  - Primary total hip replacement with a Furlong fully hydroxyapatite-coated titanium
      alloy femoral component: Results at a minimum follow-up of 20 years.
AB  - We present the extended follow-up (>= 20 years) of a series of fully
      hydroxyapatite-coated femoral components used in 72 primary total hip
      replacements (THRs). Earlier results of this cohort have been previously
      published. All procedures were performed between 1986 and 1991. The series
      involved 45 women and 15 men with 12 bilateral procedures. Their mean age at the
      time of surgery was 60 years (46 to 80) and the mean duration of follow-up was
      22.5 years (20 to 25). At final follow-up, the mean Merle d'Aubigne and Postel
      hip scores were 5.5 (4.5 to 6), 3.8 (3.5 to 5) and 3.3 (3.0 to 5.0) for pain,
      mobility and function, respectively. Of the patients 92% were very satisfied at
      the time of final follow-up. There were seven revisions: six of the acetabular
      component for aseptic loosening and one of both the stem and the acetabular
      component for loosening due to deep infection. The survival of this prosthesis at
      22.5 years with revision for any reason as the endpoint was 91.7% (95% confidence
      interval (CI) 84 to 99). Survival with aseptic loosening of the stem as the
      endpoint was 100% (95% CI 90 to 100). This prosthesis provides pain relief in the
      long term. Survival of this component is comparable to the best results for
      primary THR with any means of fixation.

PMID- 23539698
TI  - The significance of an asymmetric extension gap on routine radiographs after
      total knee replacement: A new sign and its clinical significance.
AB  - We investigated whether an asymmetric extension gap seen on routine post
      operative radiographs after primary total knee replacement (TKR) is associated
      with pain at three, six, 12 and 24 months' follow-up. On radiographs of 277
      patients after primary TKR we measured the distance between the tibial tray and
      the femoral condyle on both the medial and lateral sides. A difference was
      defined as an asymmetric extension gap. We considered three groups (no asymmetric
      gap, medial-opening and lateral-opening gap) and calculated the associations with
      the Western Ontario and McMaster Universities osteoarthritis index pain scores
      over time. Those with an asymmetric extension gap of >= 1.5 mm had a significant
      association with pain scores at three months' follow-up; patients with a medial
      opening extension gap reported more pain and patients with a lateral-opening
      extension gap reported less pain (p = 0.036). This effect was still significant
      at six months (p = 0.044), but had lost significance by 12 months (p = 0.924).
      When adjusting for multiple cofounders the improvement in pain was more
      pronounced in patients with a lateral-opening extension gap than in those with a
      medial-opening extension gap at three (p = 0.037) and six months' (p = 0.027)
      follow-up.

PMID- 23539699
TI  - Long-term (ten- to 15-year) outcome of arthroscopically assisted Elmslie-Trillat
      tibial tubercle osteotomy.
AB  - We present the ten- to 15-year follow-up of 31 patients (34 knees), who underwent
      an Elmslie-Trillat tibial tubercle osteotomy for chronic, severe patellar
      instability, unresponsive to non-operative treatment. The mean age of the
      patients at the time of surgery was 31 years (18 to 46) and they were reviewed
      post-operatively, at four years (2 to 8) and then at 12 years (10 to 15). All
      patients had pre-operative knee radiographs and Cox and Insall knee scores.
      Superolateral portal arthroscopy was performed per-operatively to document
      chondral damage and after the osteotomy to assess the stability of the
      patellofemoral joint. A total of 28 knees (82%) had a varying degree of damage to
      the articular surface. At final follow-up 25 patients (28 knees) were available
      for review and underwent clinical examination, radiographs of the knee, and Cox
      and Insall scoring. Six patients who had no arthroscopic chondral abnormality
      showed no or only early signs of osteoarthritis on final radiographs; while 12
      patients with lower grade chondral damage (grade 1 to 2) showed early to moderate
      signs of osteoarthritis and six out of ten knees with higher grade chondral
      damage (grade 3 to 4) showed marked evidence of osteoarthritis; four of these had
      undergone a knee replacement. In the 22 patients (24 knees) with complete follow
      up, 19 knees (79.2%) were reported to have a good or excellent outcome at four
      years, while 15 knees (62.5%) were reported to have the same at long-term follow
      up. The functional and radiological results show that the extent of pre
      operatively sustained chondral damage is directly related to the subsequent
      development of patellofemoral osteoarthritis.

PMID- 23539701
TI  - Mid-flexion laxity is greater after posterior-stabilised total knee replacement
      than with cruciate-retaining procedures: A computer navigation study.
AB  - There are several methods for evaluating stability of the joint during total knee
      replacement (TKR). Activities of daily living demand mechanical loading to the
      knee joint, not only in full extension, but also in mid-flexion. The purpose of
      this study was to compare the varus-valgus stability throughout flexion in knees
      treated with either cruciate-retaining or posterior-stabilised TKR, using an
      intra-operative navigation technique. A total of 34 knees underwent TKR with
      computer navigation, during which the investigator applied a maximum varus-valgus
      stress to the knee while steadily moving the leg from full extension to flexion
      both before and after prosthetic implantation. The femorotibial angle was
      measured simultaneously by the navigation system at every 10 degrees  throughout
      the range of movement. It was found that posterior-stabilised knees had more
      varus-valgus laxity than cruciate-retaining knees at all angles examined, and the
      differences were statistically significant at 10 degrees  (p = 0.0093), 20
      degrees  (p = 0.0098) and 30 degrees  of flexion (p = 0.0252).

PMID- 23539702
TI  - Intense pulsed light treatment of chronic mid-body Achilles tendinopathy: A
      double blind randomised placebo-controlled trial.
AB  - We conducted a randomised controlled trial to determine whether active intense
      pulsed light (IPL) is an effective treatment for patients with chronic mid-body
      Achilles tendinopathy. A total of 47 patients were randomly assigned to three
      weekly therapeutic or placebo IPL treatments. The primary outcome measure was the
      Victorian Institute of Sport Assessment - Achilles (VISA-A) score. Secondary
      outcomes were a visual analogue scale for pain (VAS) and the Lower Extremity
      Functional Scale (LEFS). Outcomes were recorded at baseline, six weeks and 12
      weeks following treatment. Ultrasound assessment of the thickness of the tendon
      and neovascularisation were also recorded before and after treatment. There was
      no significant difference between the groups for any of the outcome scores or
      ultrasound measurements by 12 weeks, showing no measurable benefit from treatment
      with IPL in patients with Achilles tendinopathy.

PMID- 23539703
TI  - Comparison of outcomes between proximal and distal chevron osteotomy, both with
      supplementary lateral soft-tissue release, for severe hallux valgus deformity: A
      prospective randomised controlled trial.
AB  - Severe hallux valgus deformity is conventionally treated with proximal metatarsal
      osteotomy. Distal metatarsal osteotomy with an associated soft-tissue procedure
      can also be used in moderate to severe deformity. We compared the clinical and
      radiological outcomes of proximal and distal chevron osteotomy in severe hallux
      valgus deformity with a soft-tissue release in both. A total of 110 consecutive
      female patients (110 feet) were included in a prospective randomised controlled
      study. A total of 56 patients underwent a proximal procedure and 54 a distal
      operation. The mean follow-up was 39 months (24 to 54) in the proximal group and
      38 months (24 to 52) in the distal group. At follow-up the hallux valgus angle,
      intermetatarsal angle, distal metatarsal articular angle, tibial sesamoid
      position, American Orthopaedic Foot and Ankle Society (AOFAS) hallux
      metatarsophalangeal-interphalangeal score, patient satisfaction level, and
      complications were similar in each group. Both methods showed significant post
      operative improvement and high levels of patient satisfaction. Our results
      suggest that the distal chevron osteotomy with an associated distal soft-tissue
      procedure provides a satisfactory method for correcting severe hallux valgus
      deformity.

PMID- 23539704
TI  - Latissimus dorsi tendon transfer for irreparable tears of the rotator cuff: An
      anatomical study to assess the neurovascular hazards and ways of improving tendon
      excursion.
AB  - Latissimus dorsi tendon transfer (LDTT) is technically challenging. In order to
      clarify the local structural anatomy, we undertook a morphometric study using six
      complete cadavers (12 shoulders). Measurements were made from the tendon to the
      nearby neurovascular structures with the arm in two positions: flexed and
      internally rotated, and adducted in neutral rotation. The tendon was then
      transferred and measurements were taken from the edge of the tendon to a
      reference point on the humeral head in order to assess the effect of a novel two
      stage release on the excursion of the tendon. With the shoulder flexed and
      internally rotated, the mean distances between the superior tendon edge and the
      radial nerve, brachial artery, axillary nerve and posterior circumflex artery
      were 30 mm (26 to 34), 28 mm (17 to 39), 21 mm (12 to 28) and 15 mm (10 to 21),
      respectively. The mean distance between the inferior tendon edge and the radial
      nerve, brachial artery and profunda brachii artery was 18 mm (8 to 27), 22 mm (15
      to 32) and 14 mm (7 to 21), respectively. Moving the arm to a neutral position
      reduced these distances. A mean of 15 mm (8 to 21) was gained from a standard
      soft-tissue release, and 32 mm (20 to 45) from an extensile release. These
      figures help to define further the structural anatomy of this region and the
      potential for transfer of the latissimus dorsi tendon.

PMID- 23539705
TI  - Teres major tendon transfer for patients with massive irreparable posterosuperior
      rotator cuff tears: Short-term clinical results.
AB  - Surgical repair of posterosuperior rotator cuff tears has a poorer outcome and a
      higher rate of failure compared with repairs of supraspinatus tears. In this
      prospective cohort study 28 consecutive patients with an irreparable
      posterosuperior rotator cuff tear after failed conservative or surgical treatment
      underwent teres major tendon transfer. Their mean age was 60 years (48 to 71) and
      the mean follow-up was 25 months (12 to 80). The mean active abduction improved
      from 79 degrees  (0 degrees  to 150 degrees ) pre-operatively to 105 degrees  (20
      degrees  to 180 degrees ) post-operatively (p = 0.011). The mean active external
      rotation in 90 degrees  abduction improved from 25 degrees  (0 degrees  to 70
      degrees ) pre-operatively to 55 degrees  (0 degrees  to 90 degrees ) post
      operatively (p < 0.001). The mean Constant score improved from 43 (18 to 78) pre
      operatively to 65 (30 to 86) post-operatively (p < 0.001). The median post
      operative VAS (0 to 100) for pain decreased from 63 (0 to 96) pre-operatively to
      5 (0 to 56) post-operatively (p < 0.001). In conclusion, teres major transfer
      effectively restores function and relieves pain in patients with irreparable
      posterosuperior rotator cuff tears and leads to an overall clinical improvement
      in a relatively young and active patient group with limited treatment options.

PMID- 23539700
TI  - Five-year results of a randomised controlled trial comparing mobile and fixed
      bearings in total knee replacement.
AB  - There is conflicting evidence about the merits of mobile bearings in total knee
      replacement, partly because most randomised controlled trials (RCTs) have not
      been adequately powered. We report the results of a multicentre RCT of mobile
      versus fixed bearings. This was part of the knee arthroplasty trial (KAT), where
      539 patients were randomly allocated to mobile or fixed bearings and analysed on
      an intention-to-treat basis. The primary outcome measure was the Oxford Knee
      Score (OKS) plus secondary measures including Short Form-12, EuroQol EQ-5D,
      costs, cost-effectiveness and need for further surgery. There was no significant
      difference between the groups pre-operatively: mean OKS was 17.18 (sd 7.60) in
      the mobile-bearing group and 16.49 (sd 7.40) in the fixed-bearing group. At five
      years mean OKS was 33.19 (sd 16.68) and 33.65 (sd 9.68), respectively. There was
      no significant difference between trial groups in OKS at five years (-1.12 (95%
      confidence interval -2.77 to 0.52) or any of the other outcome measures.
      Furthermore, there was no significant difference in the proportion of patients
      with knee-related re-operations or in total costs. In this appropriately powered
      RCT, over the first five years after total knee replacement functional outcomes,
      re-operation rates and healthcare costs appear to be the same irrespective of
      whether a mobile or fixed bearing is used.

PMID- 23539706
TI  - Scapular notching and osteophyte formation after reverse shoulder replacement:
      Radiological analysis of implant position in male and female patients.
AB  - This study provides recommendations on the position of the implant in reverse
      shoulder replacement in order to minimise scapular notching and osteophyte
      formation. Radiographs from 151 patients who underwent primary reverse shoulder
      replacement with a single prosthesis were analysed at a mean follow-up of 28.3
      months (24 to 44) for notching, osteophytes, the position of the glenoid
      baseplate, the overhang of the glenosphere, and the prosthesis scapular neck
      angle (PSNA). A total of 20 patients (13.2%) had a notch (16 Grade 1 and four
      Grade 2) and 47 (31.1%) had an osteophyte. In patients without either notching or
      an osteophyte the baseplate was found to be positioned lower on the glenoid, with
      greater overhang of the glenosphere and a lower PSNA than those with notching and
      an osteophyte. Female patients had a higher rate of notching than males (13.3% vs
      13.0%) but a lower rate of osteophyte formation (22.9% vs 50.0%), even though the
      baseplate was positioned significantly lower on the glenoid in females (p =
      0.009) and each had a similar mean overhang of the glenosphere. Based on these
      findings we make recommendations on the placement of the implant in both male and
      female patients to avoid notching and osteophyte formation.

PMID- 23539707
TI  - The three-dimensional morphometry of the odontoid peg and its impact on ventral
      screw osteosynthesis.
AB  - Ventral screw osteosynthesis is a common surgical method for treating fractures
      of the odontoid peg, but there is still no consensus about the number and
      diameter of the screws to be used. The purpose of this study was to develop a
      more accurate measurement technique for the morphometry of the odontoid peg (dens
      axis) and to provide a recommendation for ventral screw osteosynthesis. Images of
      the cervical spine of 44 Caucasian patients, taken with a 64-line CT scanner,
      were evaluated using the measuring software MIMICS. All measurements were
      performed by two independent observers. Intraclass correlation coefficients were
      used to measure inter-rater variability. The mean length of the odontoid peg was
      39.76 mm (SD 2.68). The mean screw entry angle alpha was 59.45 degrees  (SD
      3.45). The mean angle between the screw and the ventral border of C2 was 13.18
      degrees  (SD 2.70), the maximum possible mean converging angle of two screws was
      20.35 degrees  (SD 3.24). The measurements were obtained at the level of 66% of
      the total odontoid peg length and showed mean values of 8.36 mm (SD 0.84) for the
      inner diameter in the sagittal plane and 7.35 mm (SD 0.97) in the coronal plane.
      The mean outer diameter of the odontoid peg was 12.88 mm (SD 0.91) in the
      sagittal plane and 11.77 mm (SD 1.09) in the coronal plane. The results measured
      at the level of 90% of the total odontoid peg length were a mean of 6.12 mm (SD
      1.14) for the sagittal inner diameter and 5.50 mm (SD 1.05) for the coronal inner
      diameter. The mean outer diameter of the odontoid peg was 11.10 mm (SD 1.0) in
      the sagittal plane and 10.00 mm (SD 1.07) in the coronal plane. In order to
      calculate the necessary screw length using 3.5 mm cannulated screws, 1.5 mm
      should be added to the measured odontoid peg length when anatomical reduction
      seems possible. The cross-section of the odontoid peg is not circular but
      slightly elliptical, with a 10% greater diameter in the sagittal plane. In the
      majority of cases (70.5%) the odontoid peg offers enough room for two 3.5 mm
      cannulated cortical screws.

PMID- 23539708
TI  - The use of a zero-profile device compared with an anterior plate and cage in the
      treatment of patients with symptomatic cervical spondylosis: A preliminary
      clinical investigation.
AB  - In a retrospective cohort study we compared the clinical outcome and
      complications, including dysphagia, following anterior cervical fusion for the
      treatment of cervical spondylosis using either a zero-profile (Zero-P; Synthes)
      implant or an anterior cervical plate and cage. A total of 83 patients underwent
      fusion using a Zero-P and 107 patients underwent fusion using a plate and cage.
      The mean follow-up was 18.6 months (SD 4.2) in the Zero-P group and 19.3 months
      (SD 4.1) in the plate and cage group. All patients in both groups had significant
      symptomatic and neurological improvement. There were no significant differences
      between the groups in the Neck Disability Index (NDI) and visual analogue scores
      at final follow-up. The cervical alignment improved in both groups. There was a
      higher incidence of dysphagia in the plate and cage group on the day after
      surgery and at two months post-operatively. All patients achieved fusion and no
      graft migration or nonunion was observed. When compared with the traditional
      anterior cervical plate and cage, the Zero-P implant is a safe and convenient
      procedure giving good results in patients with symptomatic cervical spondylosis
      with a reduced incidence of dysphagia post-operatively.

PMID- 23539709
TI  - The long-term clinical outcome after pelvic ring injuries.
AB  - We report the functional and socioeconomic long-term outcome of patients with
      pelvic ring injuries. We identified 109 patients treated at a Level I trauma
      centre between 1973 and 1990 with multiple blunt orthopaedic injuries including
      an injury to the pelvic ring, with an Injury Severity Score (ISS) of >= 16. These
      patients were invited for clinical review at a minimum of ten years after the
      initial injury, at which point functional results, general health scores and
      socioeconomic factors were assessed. In all 33 isolated anterior (group A), 33
      isolated posterior (group P) and 43 combined anterior/posterior pelvic ring
      injuries (group A/P) were included. The mean age of the patients at injury was
      28.8 years (5 to 55) and the mean ISS was 22.7 (16 to 44). At review the mean
      Short-Form 12 physical component score for the A/P group was 38.71 (22.12 to
      56.56) and the mean Hannover Score for Polytrauma Outcome subjective score was
      67.27 (12.48 to 147.42), being significantly worse compared with the other two
      groups (p = 0.004 and p = 0.024, respectively). A total of 42 patients (39%) had
      a limp and 12 (11%) required crutches. Car or public transport usage was
      restricted in 16 patients (15%). Overall patients in groups P and A/P had a worse
      outcome. The long-term outcome of patients with posterior or combined
      anterior/posterior pelvic ring injuries is poorer than of those with an isolated
      anterior injury.

PMID- 23539710
TI  - Synovial fluid white cell and differential count in the diagnosis or exclusion of
      prosthetic joint infection.
AB  - Cut-off values with highest sensitivity and specificity for the synovial fluid
      white cell and differential count will facilitate the accurate diagnosis of
      infection in total knee (TKR) and total hip replacement (THR). All patients
      undergoing revision TKR or THR for suspected prosthetic joint infection between
      2009 and 2011 at two hospitals were identified. A total of 75 patients were
      included with a mean age of 70.3 years (38 to 89). Synovial fluid was aspirated
      pre-operatively and peri-prosthetic tissue samples were taken intra-operatively
      for histological and microbiological examination. Receiver operating
      characteristic (ROC) plots were constructed for white cell and differential
      counts in aspirated fluid. The optimal cut-off for TKR and THR was 1590 white
      cells/ul and 65% neutrophilia. The white cell count cut-off value identified for
      THR was notably lower than previously quoted in the literature. A cut-off value
      for white cell count in synovial aspirate in suspected prosthetic joint infection
      of between 1100 and 1700 white cells/ul is likely to be applicable to both THR
      and TKR.

PMID- 23539711
TI  - Risk factors for post-operative venous thromboembolism in patients with a
      malignancy of the lower limb.
AB  - It is important to be able to identify patients with an increased risk of venous
      thromboembolism (VTE) in order to minimise the risk of an event. We investigated
      the incidence and risk factors for post-operative VTE in 168 consecutive patients
      with a malignancy of the lower limb. The period of study included ten months
      before and 12 months after the introduction of chemical thromboprophylaxis. All
      data about the potential risk factors were identified and classified into three
      groups (patient-, surgery- and tumour-related). The outcome measure was a
      thromboembolic event within 90 days of surgery. Of the 168 patients, eight (4.8%)
      had a confirmed symptomatic deep-vein thrombosis and one (0.6%) a fatal pulmonary
      embolism. Of the 28 variables tested, age > 60 years, higher American Society of
      Anesthesiologists grade and metastatic tumour were independent risk factors for
      VTE. The overall rate of symptomatic VTE was not significantly different between
      patients who received chemical thromboprophylaxis and those who did not.
      Knowledge of these risk factors may be of value in improving the surgical outcome
      of patients with a malignancy of the lower limb.

PMID- 23539712
TI  - The value of the three-point index in predicting redisplacement of diaphyseal
      fractures of the forearm in children.
AB  - Redisplacement is the most common complication of immobilisation in a cast for
      the treatment of diaphyseal fractures of the forearm in children. We have
      previously shown that the three-point index (TPI) can accurately predict
      redisplacement of fractures of the distal radius. In this prospective study we
      applied this index to assessment of diaphyseal fractures of the forearm in
      children and compared it with other cast-related indices that might predict
      redisplacement. A total of 76 children were included. Their ages, initial
      displacement, quality of reduction, site and level of the fractures and quality
      of the casting according to the TPI, Canterbury index and padding index were
      analysed. Logistic regression analysis was used to investigate risk factors for
      redisplacement. A total of 18 fractures (24%) redisplaced in the cast. A TPI
      value of > 0.8 was the only significant risk factor for redisplacement (odds
      ratio 238.5 (95% confidence interval 7.063 to 8054.86); p < 0.001). The TPI was
      far superior to other radiological indices, with a sensitivity of 84% and a
      specificity of 97% in successfully predicting redisplacement. We recommend it for
      routine use in the management of these fractures in children.

PMID- 23539713
TI  - Expression of matrix metalloproteinases in human growth plate chondrocytes is
      enhanced at high levels of mechanical loading: A possible explanation for overuse
      injuries in children.
AB  - Matrix metalloproteinases (MMPs), responsible for extracellular matrix
      remodelling and angiogenesis, might play a major role in the response of the
      growth plate to detrimental loads that lead to overuse injuries in young
      athletes. In order to test this hypothesis, human growth plate chondrocytes were
      subjected to mechanical forces equal to either physiological loads, near
      detrimental or detrimental loads for two hours. In addition, these cells were
      exposed to physiological loads for up to 24 hours. Changes in the expression of
      MMPs -2, -3 and -13 were investigated. We found that expression of MMPs in
      cultured human growth plate chondrocytes increases in a linear manner with
      increased duration and intensity of loading. We also showed for the first time
      that physiological loads have the same effect on growth plate chondrocytes over a
      long period of time as detrimental loads applied for a short period. These
      findings confirm the involvement of MMPs in overuse injuries in children. We
      suggest that training programmes for immature athletes should be reconsidered in
      order to avoid detrimental stresses and over-expression of MMPs in the growth
      plate, and especially to avoid physiological loads becoming detrimental.

PMID- 23539714
TI  - Response to: Grimer RJ, Chandrasekar CR, Carter SR, et al. Hindquarter
      amputation: is it still needed and what are the outcomes?
AB  - We welcome letters to the Editor concerning articles that have recently been
      published. Such letters will be subject to the usual stages of selection and
      editing; where appropriate the authors of the original article will be offered
      the opportunity to reply.

PMID- 23539716
TI  - Use and misuse of statins after ACS: analysis of a prescription database of a
      community setting of 2,042,968 subjects.
AB  - AIMS: To assess in a community setting how patients discharged alive after an
      acute coronary syndrome (ACS) are treated with statins. Specifically, the rate of
      prescription, the dosages, and 1-year adherence have been evaluated. METHODS AND
      RESULTS: From the ARNO Observatory, we carried out a record linkage analysis of
      discharge records for ACS and prescription databases, which included 2,042,968
      subjects of seven local health authorities from northern to southern Italy. The
      accrual period lasted from 1 January to 30 June 2007. Logistic regression
      analysis was performed to identify the independent predictors of prescription
      continuity. Of the 2,042,968 subjects, 1.50/00 were hospitalised for ACS over the
      6 months, 58% of patients were aged more than 70 years, and females accounted for
      33% of the cases. In-hospital all-cause death was 7.4%. Of the patients
      discharged alive, 80.7% received a statin treatment. High dosage of statins were
      used only in a minority of cases. After 1-year follow up, adherence to treatment
      was observed in 67.2% of patients. Older age and the presence of comorbidities
      were independently associated with a better prescription continuity, while
      presence of cancer or depression was associated with a poor prescription
      continuity. CONCLUSION: In a community setting, the rate of prescription of
      statins seems to be satisfactory. However, the dosages of statins suggest that
      the recommendation to use intensive statin treatment seems to be not adequately
      followed. Further, prescription continuity over time was suboptimal. There is
      still a relevant gap between evidence-based recommendations and what actually
      happens in routine clinical practice.

PMID- 23539717
TI  - Cost-effectiveness analysis of coronary artery disease screening in HIV-infected
      men.
AB  - BACKGROUND: HIV-infected patients are at increased risk of coronary artery
      disease (CAD). We evaluated the cost-effectiveness of cardiac screening for HIV
      positive men at intermediate or greater CAD risk. DESIGN: We developed a lifetime
      microsimulation model of CAD incidence and progression in HIV-infected men.
      METHODS: Input parameters were derived from two HIV cohort studies and the
      literature. We compared no CAD screening with stress testing and coronary
      computed tomography angiography (CCTA)-based strategies. Patients with test
      results indicating 3-vessel/left main CAD underwent invasive coronary angiography
      (ICA) and received coronary artery bypass graft surgery. In the stress testing +
      medication and CCTA + medication strategies, patients with 1-2-vessel CAD results
      received lifetime medical treatment without further diagnostics whereas in the
      stress testing + intervention and CCTA + intervention strategies, patients with
      these results underwent ICA and received percutaneous coronary intervention.
      RESULTS: Compared to no screening, the stress testing + medication, stress
      testing + intervention, CCTA + medication, and CCTA + intervention strategies
      resulted in 14, 11, 19, and 14 quality-adjusted life days per patient and
      incremental cost-effectiveness ratios of 49,261, 57,817, 34,887 and 56,518 Euros
      per quality-adjusted life year (QALY), respectively. Screening only at higher CAD
      risk thresholds was more cost-effective. Repeated screening was clinically
      beneficial compared to one-time screening, but only stress testing + medication
      every 5 years remained cost-effective. At a willingness-to-pay threshold of
      83,000 ?/QALY (~ 100,000 US$/QALY), implementing any CAD screening was cost
      effective with a probability of 75-95%. CONCLUSIONS: Screening HIV-positive men
      for CAD would be clinically beneficial and comes at a cost-effectiveness ratio
      comparable to other accepted interventions in HIV care.

PMID- 23539718
TI  - Idiopathic adult growth hormone deficiency.
AB  - GH secretion is controlled by hypothalamic as well as intrapituitary and
      peripheral signals, all of which converge upon the somatotroph, resulting in
      integrated GH synthesis and secretion. Enabling an accurate diagnosis of
      idiopathic adult GH deficiency (IAGHD) is challenged by the pulsatility of GH
      secretion, provocative test result variability, and suboptimal GH assay
      standardization. The spectrum between attenuated GH secretion associated with the
      normal aging process and with obesity and truly well-defined IAGHD is not
      distinct and may mislead the diagnosis. Adult-onset GHD is mainly caused by an
      acquired pituitary deficiency, commonly including prior head/neck irradiation, or
      an expanding pituitary mass causing functional somatotroph compression. To what
      extent rare cryptic causes account for those patients seemingly classified as
      IAGHD is unclear. About 15% of patients with adult GHD and receiving GH
      replacement in open-label surveillance studies are reported as being due to an
      idiopathic cause. These patients may also reflect a pool of subjects with an as
      yet to be determined occult defect, or those with unclear or incomplete medical
      histories (including forgotten past sports head injury or motor vehicle
      accident). Therefore, submaximal diagnostic evaluation likely leads to an
      inadvertent diagnosis of IAGHD. In these latter cases, adherence to rigorous
      biochemical diagnostic criteria and etiology exclusion may result in
      reclassification of a subset of these patients to a distinct known acquired
      etiology, or as GH-replete. Accordingly, rigorously verified IAGHD likely
      comprises less than 10% of adult GHD patients, an already rare disorder.
      Regardless of etiology, patients with adult GHD, including those with IAGHD,
      exhibit a well-defined clinical phenotype including increased fat mass, loss of
      lean muscle mass, decreased bone mass, and enhanced cardiac morbidity. Definition
      of unique efficacy and dosing parameters for GH replacement and resultant
      therapeutic efficacy markers in true IAGHD requires prospective study.

PMID- 23539719
TI  - Clinical review: Clinical utility of TSH receptor antibodies.
AB  - CONTEXT: TSH receptor antibodies (TRAb) cause Graves' disease (GD)
      hyperthyroidism. Widely available TRAb measurement methods have been
      significantly improved recently. However, the role of TRAb measurement in the
      differential diagnosis of hyperthyroidism, the prediction of remission of GD
      hyperthyroidism, the prediction of fetal/neonatal thyrotoxicosis, and the
      clinical assessment of Graves' ophthalmopathy (GO) are controversial. EVIDENCE
      ACQUISITION: We reviewed and analyzed the literature reporting primary data on
      the clinical use of TRAb. We focused our analyses on clinical studies analyzing
      third-generation TRAb assays. EVIDENCE SYNTHESIS: The performance of TRAb in the
      differential diagnosis of overt hyperthyroidism is excellent, with sensitivity
      and specificity in the upper 90%. TRAb can accurately predict short-term relapses
      of hyperthyroidism after a course of antithyroid drugs but are less effective in
      predicting long-term relapses or remissions. Pregnancies in women with GD with
      negative TRAb are highly unlikely to result in fetal hyperthyroidism, whereas
      high titers of TRAb in pregnancy require careful fetal monitoring. GD patients
      with GO frequently have high TRAb levels. However, there are insufficient data to
      use the test to predict the clinical course of GO and response to treatment.
      CONCLUSIONS: Third-generation TRAb assays are suitable in the differential
      diagnosis of hyperthyroidism. In GD, TRAb should be tested before deciding
      whether methimazole can be stopped. TRAb should be used in pregnant women with GD
      to assess the risk of fetal thyrotoxicosis. The use of TRAb in GO requires
      further studies.

PMID- 23539720
TI  - Humanized medium (h7H) allows long-term primary follicular thyroid cultures from
      human normal thyroid, benign neoplasm, and cancer.
AB  - CONTEXT: Mechanisms of thyroid physiology and cancer are principally studied in
      follicular cell lines. However, human thyroid cancer lines were found to be
      heavily contaminated by other sources, and only one supposedly normal-thyroid
      cell line, immortalized with SV40 antigen, is available. In primary culture,
      human follicular cultures lose their phenotype after passage. We hypothesized
      that the loss of the thyroid phenotype could be related to culture conditions in
      which human cells are grown in medium optimized for rodent culture, including
      hormones with marked differences in its affinity for the relevant rodent/human
      receptor. OBJECTIVE: The objective of the study was to define conditions that
      allow the proliferation of primary human follicular thyrocytes for many passages
      without losing phenotype. METHODS: Concentrations of hormones, transferrin,
      iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted
      within normal homeostatic human serum ranges. Single cultures were identified by
      short tandem repeats. Human-rodent interspecies contamination was assessed.
      RESULTS: We defined an humanized 7 homeostatic additives medium enabling growth
      of human thyroid cultures for more than 20 passages maintaining thyrocyte
      phenotype. Thyrocytes proliferated and were grouped as follicle-like structures;
      expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and
      thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3.
      Using these conditions, we generated a bank of thyroid tumors in culture from
      normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and
      carcinomas. CONCLUSIONS: Using appropriate culture conditions is essential for
      phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture
      generated under humanized humanized 7 homeostatic additives culture conditions
      will provide a much-needed tool to compare similarly growing cells from normal vs
      pathological origins and thus to elucidate the molecular basis of thyroid
      disease.

PMID- 23539721
TI  - Referral bias in defining the phenotype and prevalence of obesity in polycystic
      ovary syndrome.
AB  - BACKGROUND: The described phenotype of the polycystic ovary syndrome (PCOS) has
      been primarily based on findings in a referred (self or otherwise) population. It
      is possible that the phenotype of PCOS would be different if the disorder were to
      be detected and studied in its natural (unbiased) state. OBJECTIVE: Our objective
      was to compare the phenotype of PCOS detected in an unselected population with
      that identified in a referral population. PARTICIPANTS: Participants included 292
      PCOS patients identified at a tertiary care outpatient facility (referral PCOS)
      and 64 PCOS women (unselected PCOS) identified through the screening of a
      population of 668 seeking a pre-employment physical. Among the women undergoing a
      pre-employment physical, 563 did not demonstrate features of the disorder
      (unselected controls). All PCOS subjects met the National Institutes of Health
      1990 criteria for the disorder. MAIN OUTCOME MEASURES: We estimated prevalence of
      obesity and severity of disease burden. RESULTS: Referral PCOS subjects had
      greater mean body mass index and hirsutism score and higher degrees of
      hyperandrogenemia, were more likely to be non-Hispanic White (83.90%), and
      demonstrated a more severe PCOS subphenotype than unselected PCOS or unselected
      controls. The prevalence of obesity and severe obesity in referral PCOS was 2.3
      and 2.5 times greater than estimates of the same in unselected PCOS and 2.2 and
      3.8 times greater than estimates in unselected controls, respectively.
      Alternatively, unselected PCOS subjects had a prevalence of obesity and severe
      obesity and a mean body mass index similar to those of the general population
      from which they were derived. CONCLUSION: The phenotype of PCOS, including the
      racial/ethnic mix, severity of presentation, and rate of obesity, is affected
      significantly by whether the PCOS subject arises from a referral population or
      through unselected screening, likely reflecting the degree of patient concern and
      awareness and access to healthcare.

PMID- 23539722
TI  - Variation in the management of thyroid cancer.
AB  - CONTEXT: Little is known about practice patterns in thyroid cancer, a cancer that
      is increasing in incidence. OBJECTIVE: We sought to identify aspects of thyroid
      cancer management that have the greatest variation. DESIGN/SETTING/PARTICIPANTS:
      We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals
      affiliated with the US National Cancer Database. Physicians were asked questions
      in the following four domains: thyroid surgery, radioactive iodine use, thyroid
      hormone replacement postsurgery, and long-term thyroid cancer management. We
      calculated the ratio of observed variation to hypothetical maximum variation
      under the assumed distribution of the response. Ratios closer to 1 indicate
      greater variation. RESULTS: We had a 66% response rate. We found variation in
      multiple aspects of thyroid cancer management, including the role of central
      lymph node dissections (variation, 0.99; 95% confidence interval [CI], 0.98
      1.00), the role of pretreatment scans before radioactive iodine treatment
      (variation, 1.00; 95% CI, 0.98-1.00), and all aspects of long-term thyroid cancer
      management, including applications of ultrasound (variation, 0.97; 95% CI, 0.93
      0.99) and radioactive iodine scans (variation, 0.99; 95% CI, 0.97-1.00). For the
      management of small thyroid cancers, variation exists in all domains, including
      optimal extent of surgery (variation, 0.91; 95% CI, 0.88-0.94) and the role of
      both radioactive iodine treatment (variation, 0.91; 95% CI, 0.89-0.93) and
      suppressive doses of thyroid hormone replacement (variation, 1.00; 95% CI, 0.99
      1.00). CONCLUSION: We identified areas of variation in thyroid cancer management.
      To reduce the variation and improve the management of thyroid cancer, there is a
      need for more research and more research dissemination.

PMID- 23539724
TI  - Free and total plasma cortisol measured by immunoassay and mass spectrometry
      following ACTH1-24 stimulation in the assessment of pituitary patients.
AB  - CONTEXT: Measurement of plasma cortisol by immunoassay after ACTH1-24 stimulation
      is used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Liquid
      chromatography-tandem mass spectrometry (LCMS) has greater analytical specificity
      than immunoassay and equilibrium dialysis allows measurement of free plasma
      cortisol. OBJECTIVE: We investigated the use of measuring total and free plasma
      cortisol by LCMS and total cortisol by immunoassay during an ACTH1-24 stimulation
      test to define HPA status in pituitary patients. DESIGN AND SETTING: This was a
      case control study conducted in a clinical research facility. PARTICIPANTS: We
      studied 60 controls and 21 patients with pituitary disease in whom HPA
      sufficiency (n = 8) or deficiency (n = 13) had been previously defined.
      INTERVENTION: Participants underwent 1 MUg ACTH(1-24) intravenous and 250 MUg
      ACTH1-24 intramuscular ACTH1-24 stimulation tests. MAIN OUTCOME MEASURES:
      Concordance of ACTH1-24-stimulated total and free plasma cortisol with previous
      HPA assessment. RESULTS: Total cortisol was 12% lower when measured by
      immunoassay than by LCMS. Female sex and older age were positively correlated
      with ACTH1-24-stimulated total and free cortisol, respectively. Measurements of
      total cortisol by immunoassay and LCMS and free cortisol 30 minutes after 1 MUg
      and 30 and 60 minutes after 250 MUg ACTH1-24 were concordant with previous HPA
      axis assessment in most pituitary patients. However, free cortisol had greater
      separation from the diagnostic cutoff than total cortisol. CONCLUSIONS:
      Categorization of HPA status by immunoassay and LCMS after ACTH1-24 stimulation
      was concordant with previous assessment in most pituitary patients. Free cortisol
      may have greater clinical use in patients near the diagnostic threshold.

PMID- 23539723
TI  - Subclinical hypothyroidism and risk for incident myocardial infarction among
      postmenopausal women.
AB  - CONTEXT: Subclinical hypothyroidism (SCH) has been associated with an increased
      risk for cardiovascular disease. However, few studies have specifically examined
      the association between SCH and myocardial infarction (MI), and the relationship
      is poorly understood. OBJECTIVES: The purpose of this study was to evaluate
      incident MI risk in relation to SCH and severities of SCH among postmenopausal
      women. METHODS: We used a population-based nested case-cohort design within the
      Women's Health Initiative observational study to examine the association between
      SCH and incident first-time MI risk among postmenopausal women in the United
      States. SCH was assessed using blood specimens collected at baseline.
      Participants presenting with normal free T4 levels and with thyrotropin levels of
      greater than 4.68-6.99 mU/L or 7.00 mU/L or greater were defined as having mild
      SCH or moderate/severe SCH, respectively. MI cases were centrally adjudicated by
      trained Women's Health Initiative staff. The primary analysis included 736
      incident MI cases and 2927 randomly selected subcohort members. Multivariable
      adjusted Cox-proportional hazard models were used to assess MI risk in relation
      to SCH. RESULTS: Compared with euthyroid participants, the multivariable adjusted
      hazard ratio (HR) for participants with any SCH was 1.05 [95% confidence interval
      (CI) 0.77-1.44]. HRs for participants with mild SCH, moderate/severe SCH, and
      moderate/severe SCH and the presence of antithyroid peroxidase antibodies (TPOAb)
      were 0.99 (95% CI 0.67-1.46), 1.19 (95% CI 0.72-1.96), and 0.90 (95% CI 0.47
      1.74), respectively. CONCLUSION: We did not find evidence to suggest that SCH is
      associated with increased MI risk among a population of predominantly older
      postmenopausal women with no prior history of MI.

PMID- 23539725
TI  - Identification of gene expression profiles associated with cortisol secretion in
      adrenocortical adenomas.
AB  - CONTEXT: The cortisol secretion of adrenocortical adenomas can be either subtle
      or overt. The mechanisms leading to the autonomous hypersecretion of cortisol are
      unknown. OBJECTIVE: The objective of the study was to identify the gene
      expression profile associated with the autonomous and excessive cortisol
      secretion of adrenocortical adenomas. PATIENTS AND METHODS: The transcriptome of
      22 unilateral adrenocortical adenomas (5 nonsecreting, 6 subclinical cortisol
      producing, 11 cortisol producing) was studied and correlated with cortisol
      secretion. Phosphodiesterase 8B (PDE8B) expression was measured by Western blot.
      RESULTS: Unsupervised clustering identified 2 groups of adenomas with a
      difference in secretion level (P = .008). Cluster 1 included only cortisol
      producing adenomas (8 of 11), whereas cluster 2 was an admixture of the
      nonsecreting, the subclinical cortisol-secreting, and 3 of the 11 cortisol
      secreting adenomas (Fisher exact, P = .002). This cluster was driven by genes
      related to cortisol secretion and to extracellular matrix. More than 3000 genes
      correlated with cortisol secretion. Among the positively correlated were the
      steroidogenic enzymes, genes involved in cholesterol metabolism, and glutathione
      S-transferases. Among the negatively correlated genes were genes related to
      transcripts translation and the transcription factor GATA-6. The PDE8B, which
      inactivates the protein kinase A pathway, unexpectedly showed the strongest
      positive correlation with cortisol secretion, confirmed by Western blot. The
      protein kinase A-activity to cAMP ratio was increased in adenomas with high PDE8B
      levels, suggesting counterregulation to limit downstream activation of the
      pathway. CONCLUSION: The transcriptome of adrenocortical adenomas reveals a major
      association with cortisol secretion and identifies specific groups of genes
      implicated in steroid secretion, suggesting that cAMP signaling alterations might
      be frequent in cortisol-secreting adenomas.

PMID- 23539726
TI  - First report of bilateral pheochromocytoma in the clinical spectrum of HIF2A
      related polycythemia-paraganglioma syndrome.
AB  - CONTEXT: Molecular genetic research has so far resulted in the identification of
      10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO)
      or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs
      and somatostatinomas associated with congenital polycythemia due to somatic
      mutations in HIF2A has been reported. OBJECTIVE: The aim of the study was to
      define the genetic defect in a new case of bilateral PHEO and multiple PGLs
      associated with congenital polycythemia. PATIENT: A female patient presented with
      neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4
      mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs.
      There was no family history of any neuroendocrine tumor or polycythemia. Surgical
      removal of the tumors only temporarily normalized plasma erythropoietin (Epo)
      levels and discontinued phlebotomies. No germline mutations were initially
      detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated
      with polycythemia. The PHEOs presented with a typical noradrenergic biochemical
      phenotype. RESULTS: A heterozygous missense mutation (c.1589C>T) was identified
      in exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2alpha
      protein with valine (A530V). This somatic mutation was detected in the tissue
      from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led
      to stabilization of HIF-2alpha and hence a gain-of-function phenotype, as in
      previously published studies. CONCLUSION: This case represents the first
      association of a somatic HIF2A gain-of-function mutation with PHEO and congenital
      polycythemia, and it alerts physicians to perform proper genetic screening in
      patients presenting with multiple norepinephrine-producing PHEOs and
      polycythemia. This report also extends the previous findings of a new syndrome of
      only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.

PMID- 23539727
TI  - Desiccated thyroid extract compared with levothyroxine in the treatment of
      hypothyroidism: a randomized, double-blind, crossover study.
AB  - CONTEXT: Patients previously treated with desiccated thyroid extract (DTE), when
      being switched to levothyroxine (L-T4), occasionally did not feel as well despite
      adequate dosing based on serum TSH levels. OBJECTIVE: Our objective was to
      investigate the effectiveness of DTE compared with L-T4 in hypothyroid patients.
      DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study at a
      tertiary care center. PATIENTS: Patients (n = 70, age 18-65 years) diagnosed with
      primary hypothyroidism on a stable dose of L-T4 for 6 months were included in the
      study. INTERVENTION: Patients were randomized to either DTE or L-T4 for 16 weeks
      and then crossed over for the same duration. OUTCOME MEASURES: Biochemical and
      neurocognitive tests at baseline and at the end of each treatment period were
      evaluated. RESULTS: There were no differences in symptoms and neurocognitive
      measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9
      +/- 36.4 lb vs 175.7 +/- 37.7 lb, P < .001). At the end of the study, 34 patients
      (48.6%) preferred DTE, 13 (18.6%) preferred L-T4, and 23 (32.9%) had no
      preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb
      during the DTE treatment, and their subjective symptoms were significantly better
      while taking DTE as measured by the general health questionnaire-12 and thyroid
      symptom questionnaire (P < .001 for both). Five variables were predictors of
      preference for DTE. CONCLUSION: DTE therapy did not result in a significant
      improvement in quality of life; however, DTE caused modest weight loss and nearly
      half (48.6%) of the study patients expressed preference for DTE over L-T4. DTE
      therapy may be relevant for some hypothyroid patients.

PMID- 23539728
TI  - SRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) shows high heritability, yet
      efforts to find predisposing genes have been largely negative. OBJECTIVES: The
      objective of this study was to identify susceptibility genes for PTC. METHODS: A
      genome-wide linkage analysis was performed in 38 families. Targeted association
      study and screening were performed in 2 large cohorts of PTC patients and
      controls. Candidate DNA variants were tested in functional studies. RESULTS:
      Linkage analysis and association studies identified the Slit-Robo Rho GTPase
      activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two
      missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain
      segregated with the disease in 1 family each. One missense variant, R617C,
      located in the RhoGAP domain occurred in 1 family. Biochemical assays
      demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was
      severely impaired by the Q149H and R617C variants. CONCLUSIONS: Our findings
      suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a
      low-penetrant gene, possibly of a modifier type.

PMID- 23539729
TI  - Predominance of beta-cell neogenesis rather than replication in humans with an
      impaired glucose tolerance and newly diagnosed diabetes.
AB  - CONTEXT: A decrease in pancreatic beta-cell mass is involved in the development
      of type 2 diabetes. OBJECTIVE: The purpose of this study was to evaluate the beta
      cell mass and the incidence of beta-cell neogenesis, replication, and apoptosis
      at both the prediabetic and diabetic stages. METHODS: We conducted a cross
      sectional study of pancreatic tissues obtained from 42 patients undergoing a
      pancreatectomy who were classified into 4 groups: normal glucose tolerance (n =
      11), impaired glucose tolerance (n = 11), newly diagnosed diabetes (n = 10), and
      long-standing type 2 diabetes (n = 10). RESULTS: The relative beta-cell area
      decreased and the beta-cell apoptosis increased during the development of
      diabetes. The number of single and clustered beta-cells, some of which
      coexpressed nestin, increased in the patients with impaired glucose tolerance and
      newly diagnosed diabetes. The prevalence of cells positive for both insulin and
      glucagon or somatostatin also increased in these patients compared with those
      with normal glucose tolerance. These double-positive cells were mainly localized
      in single and clustered beta-cells, rather than large islets, and were also
      positive for Pdx1 or Ngn3. The percentage of insulin-positive cells embedded
      within ducts increased in the impaired glucose tolerance group. There were no
      significant differences in the incidence of cells positive for both insulin and
      Ki67 among the groups. CONCLUSIONS: These results suggest that beta-cell
      neogenesis, rather than replication, predominates during impaired glucose
      tolerance and newly diagnosed diabetes in humans and may serve as a compensatory
      mechanism for the decreased beta-cell mass.

PMID- 23539730
TI  - Aldosterone excess impairs first phase insulin secretion in primary
      aldosteronism.
AB  - CONTEXT: Primary aldosteronism (PA) represents the most frequent cause of
      secondary arterial hypertension. Conflicting data have been published regarding
      the effect of aldosterone excess on glucose metabolism. OBJECTIVE: Our aim was to
      analyze insulin sensitivity and beta-cell function in a cohort of PA patients.
      Prospective follow-up investigations were performed in a subgroup of patients
      before and after adrenalectomy to assess the metabolic outcome. DESIGN: Oral
      glucose tolerance test, combined intravenous glucose tolerance test,
      hyperinsulinemic-euglycemic glucose clamp test, and arginine test were carried
      out after a 12-hour fasting period. PATIENTS: Twenty-two consecutive patients
      with both unilateral aldosterone-producing adenoma and bilateral idiopathic
      adrenal hyperplasia were recruited through the Munich center of the German Conn's
      Registry. The control group of patients with essential hypertension (n = 11) of
      corresponding age and body mass index was recruited from our hypertension unit. A
      normotensive cohort (n = 11) served as a further control group. RESULTS: At
      baseline, first-phase insulin reaction in intravenous glucose tolerance test was
      significantly reduced in patients with PA as compared to normal controls (36.0
      [24.0; 58.7] vs 90.1 [52.6; 143.8] MUU/mL, P = .031) and lower in comparison to
      essential hypertension without reaching statistical significance (53.2 [30.8;
      73.3] MUU/mL, P = .123). The study was repeated 6 months after unilateral
      adrenalectomy in 9 consecutive patients with aldosterone-producing adenoma. At
      this time point, blood pressure had been normalized in most of the patients while
      body mass index remained unchanged (26.9 [25.5; 37.6] vs 27.5 [25.1; 35.6]
      kg/m(2), P = .401). First-phase insulin reaction in response to glucose
      significantly increased at follow-up (from 36.0 [25.5; 58.7] to 48.5 [40.4; 95.2]
      MUU/mL, P = .038, n = 9). In contrast, insulin sensitivity and response to iv
      arginine did not differ before and after adrenalectomy. CONCLUSION: Aldosterone
      excess has a direct negative effect on beta-cell function in patients with PA.
      After adrenalectomy, glucose-induced first-phase insulin secretion improves
      significantly in the patients.

PMID- 23539731
TI  - Human red blood cells alterations in primary aldosteronism.
AB  - CONTEXT: Aldosterone (Aldo) effects include NADPH oxidase activation involved in
      Aldo-related oxidative stress. Red blood cells (RBCs) are particularly sensitive
      to oxidative assault, and both the formation of high molecular weight aggregates
      (HMWAs) and the diamide-induced Tyr phosphorylation (Tyr-P) level of membrane
      band 3 can be used to monitor their redox status. OBJECTIVE: The Aldo-related
      alterations in erythrocytes were evaluated by comparing in vitro evidence.
      DESIGN: This was a multicenter comparative study. STUDY PARTICIPANTS: The study
      included 12 patients affected by primary aldosteronism (PA) and 6 healthy control
      subjects (HCs), whose RBCs were compared with those of patients with PA. For in
      vitro experiments, RBCs from HCs were incubated with increasing Aldo
      concentrations. MAIN OUTCOME MEASURES: The Tyr-P level, band 3 HMWA formation,
      and autologous IgG binding were evaluated. RESULTS: In patients with PA, both Tyr
      P levels and band 3 HMWAs were higher than those in HCs. RBCs from HCs were
      treated with increasing Aldo concentrations in both platelet-poor plasma (PPP)
      and charcoal-stripped (CS)-PPP. Results showed that Aldo had dose- and time
      dependent effects on band 3 Tyr-P and HMWA formation in CS-PPP more than in PPP.
      These effects were almost completely prevented by canrenone or cortisol. Aldo
      related membrane alterations led to increased autologous IgG binding.
      CONCLUSIONS: Erythrocytes from patients with PA show oxidative-like stress
      evidenced by increased HMWA content and diamide-induced band 3 Tyr-P level. Aldo
      effects are mediated by the mineralocorticoid receptor, as suggested by the
      inhibitory effects of canrenone, an antagonist of Aldo. In CS-PPP, in which Aldo
      induces remarkable membrane alterations leading to IgG binding, Aldo may be
      responsible for premature RBC removal from circulation.

PMID- 23539732
TI  - Linear association between household income and metabolic control in children
      with insulin-dependent diabetes mellitus despite free access to health care.
AB  - BACKGROUND: In health care systems with a user fee, the impact of socioeconomic
      factors on pediatric insulin-dependent diabetes mellitus (IDDM) control could be
      due to the cost of accessing care. HYPOTHESIS: There is a linear association
      between household income and the average glycosylated hemoglobin (HbA1c) of
      children and adolescents with IDDM despite free access to health care. METHODS:
      We used a linear regression model to examine the association between normalized
      average HbA1c of 1766 diabetic children (diagnosed at our institution from 1980
      to 2011 before 17 years of age) and the median household income of their
      neighborhoods (obtained from Statistics Canada, 2006 Census data). RESULTS: We
      found a negative linear association (P < .001; r = -0.2) between the level of
      income and metabolic control assessed by HbA1c after controlling for sex, age at
      diagnosis, duration of diabetes, ethnicity, geographical factors, frequency of
      visits, current age (as a proxy for change in practice over time), and change of
      measurement methods of HbA1c across time. For every increase of $15,000 in annual
      income, HbA1c decreased by 0.1%. CONCLUSION: We report a linear association of
      household income with metabolic control of IDDM in childhood. Given that Canada
      has a system of free universal access to health care, confounding by access to
      care is unlikely. Considering the impact of poorly controlled IDDM in childhood
      on the development of long-term complications, our findings suggest that the
      higher complication rate found in adults of low socioeconomic status might
      originate from the poor control that they experienced in childhood. Support for
      the care of IDDM children from low-income neighborhoods should be increased.

PMID- 23539733
TI  - Sustained improvements in plasma ACTH and clinical status in a patient with
      Nelson's syndrome treated with pasireotide LAR, a multireceptor somatostatin
      analog.
AB  - CONTEXT: Nelson's syndrome refers to aggressive pituitary corticotroph adenoma
      growth after bilateral adrenalectomy for treatment of Cushing's disease (CD).
      Pasireotide, a novel somatostatin analog, has been effective in treating CD.
      Here, the first case report of a patient with Nelson's syndrome treated with
      pasireotide is presented. CASE PRESENTATION: A 55-year-old female was diagnosed
      with CD in 1973 at age 15 years and underwent bilateral adrenalectomy 1 year
      later. She subsequently developed Nelson's syndrome and underwent multiple
      surgeries and radiotherapy for adenoma growth. After presentation with ocular
      pain, third cranial nerve palsy, and a finding of suprasellar tumor enlargement
      with hemorrhage, she began pasireotide long-acting release 60 mg/28 days im. At
      baseline, fasting plasma ACTH was 42 710 pg/mL (normal, 5-27 pg/mL), and fasting
      plasma glucose was 98 mg/dL. After 1 month, ACTH declined to 4272 pg/mL, and it
      has remained stable over 19 months of follow-up. Hyperpigmentation progressively
      improved. Magnetic resonance imaging scans show reduction in the suprasellar
      component. Fasting plasma glucose increased to 124 mg/dL, and the patient
      underwent diabetes management. EVIDENCE ACQUISITION AND SYNTHESIS: In this
      clinical case seminar, the current understanding of the treatment of Nelson's
      syndrome and the use of pasireotide in CD are summarized. CONCLUSION: A case of
      Nelson's syndrome with clinically significant and dramatic biochemical and
      clinical responses to pasireotide administration is reported. Hyperglycemia was
      noted after pasireotide administration. Pasireotide may represent a useful tool
      in the medical management of Nelson's syndrome. Further study of the potential
      benefits and risks of pasireotide in this population is necessary.

PMID- 23539734
TI  - RAS mutations in thyroid FNA specimens are highly predictive of predominantly low
      risk follicular-pattern cancers.
AB  - INTRODUCTION: RAS mutations are common in thyroid tumors and confer a high risk
      of cancer when detected in fine-needle aspiration (FNA) specimens. Specific
      characteristics of RAS-positive thyroid cancers are not well described. METHODS:
      From April 2007 to April 2009, 921 consecutive patients undergoing FNA were
      evaluated prospectively with a panel of molecular markers. Ultrasonographic,
      cytological, histological, and surgical outcomes were retrospectively assessed.
      RESULTS: Sixty-eight aspirates from 66 patients were positive for RAS mutations
      including 63 cytologically indeterminate (93%), 3 malignant (4%), and 2 benign
      (3%) specimens. Cancer was histologically confirmed in 52 of 63 aspirates (83%)
      including the following: 46 papillary thyroid cancers, 4 follicular thyroid
      cancers, 1 medullary cancer, and 1 anaplastic cancer. All 46 RAS-positive
      papillary thyroid cancers, including 1 metastatic cancer, had follicular variant
      histology papillary thyroid cancer; only 11 tumors demonstrated vascular/capsular
      invasion and 4 had infiltrative growth. Of 48 patients with differentiated
      thyroid cancer, lymph node metastasis was uncommon and bilateral cancer was
      present in 48%. Only 33% of malignant nodules were suspicious by preoperative
      ultrasonography. At a mean follow-up of 22 months, 31 of 35 differentiated
      thyroid cancer patients (89%) have no evidence of recurrence, 4 patients (9%)
      have detectable thyroglobulin, 1 patient has bone metastases, and both patients
      with medullary and anaplastic cancer have died. CONCLUSION: Most RAS-positive
      thyroid cancers have indeterminate cytology, lack suspicious ultrasound features,
      and are histologically low-grade follicular variant histology papillary thyroid
      cancer. Lymph node and distant metastases are uncommon but bilateral disease is
      frequent. Total thyroidectomy should be considered for initial surgical
      management of most patients with RAS-positive FNA results. The role of
      prophylactic lymphadenectomy remains unclear.

PMID- 23539735
TI  - CD26/DPP4 levels in peripheral blood and T cells in patients with type 2 diabetes
      mellitus.
AB  - CONTEXT: Dipeptidyl peptidase 4 (CD26/DPP4) is expressed on blood T cells and
      also circulates in a soluble form (sCD26/DPP4). OBJECTIVE: We aimed to evaluate
      blood T cell and circulating CD26/DPP4 and its association with metabolic
      parameters in patients with type 2 diabetes mellitus (T2DM). DESIGNS: We measured
      CD26/DPP4 expression (percentage of CD26(+) cells using flow cytometry) on CD4(+)
      and CD8(+) T cells, serum CD26/DPP4 level and activity, and various metabolic
      parameters in T2DM patients not on DPP4 inhibitor therapy (n = 148). Nondiabetic
      subjects (n = 50) were included as a control group. RESULTS: Compared with the
      healthy controls, CD26/DPP4 expression on CD4(+) T cells and CD8(+) T cells was
      higher in T2DM patients. Serum CD26/DPP4 levels and enzymatic activities were
      also higher in patients with T2DM than in the control group only when metformin
      and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or
      thiazolidinedione-treated T2DM patients had lower values compared with other T2DM
      patients. Various parameters in T2DM patients were related to CD26/DPP4
      expression on the T cells (hemoglobin A1c), serum sCD26/DPP4 (hemoglobin A1c and
      insulin resistance assessed by updated homeostasis model assessment), and serum
      CD26/DPP4 activity (insulin resistance assessed by updated homeostasis model
      assessment, gamma-glutamyl transferase, and alanine aminotransferase) by
      multivariate analyses. After active glucose control for 12 weeks in drug-naive
      T2DM patients (n = 50), CD26/DPP4 expression on blood T cells was significantly
      decreased. CONCLUSIONS: Our results suggest that the CD26/DPP4 level on blood T
      cells was associated with glucose control status in patients with T2DM.

PMID- 23539736
TI  - Elevated 1-hour postload plasma glucose levels identify subjects with normal
      glucose tolerance but impaired beta-cell function, insulin resistance, and worse
      cardiovascular risk profile: the GENFIEV study.
AB  - CONTEXT: In subjects with normal glucose tolerance (NGT) 1-hour postload plasma
      glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2
      diabetes (T2DM) and is associated with subclinical atherosclerosis. OBJECTIVE:
      The purpose of this study was to evaluate beta-cell function, insulin resistance,
      and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of
      >155 mg/dL. PATIENTS AND METHODS: The GENFIEV (Genetics, PHYsiopathology, and
      Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals
      at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for
      assessment of plasma glucose and C-peptide for mathematical modeling of beta-cell
      function (derivative and proportional control). Fasting insulin, lipid profile,
      and clinical parameters were determined as well. RESULTS: A 1-hour OGTT glucose
      of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting
      glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with
      IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n =
      474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant
      and had worse beta-cell function than those with 1-hour OGTT glucose of <=155
      mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein
      cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT
      glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower
      compared with that in subjects with NGT with 1-hour OGTT glucose of <=155 mg/dL.
      Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155
      mg/dL had comparable cardiovascular risk profile and insulin resistance but
      slightly better beta-cell function. CONCLUSIONS: Among subjects with NGT, those
      with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired
      beta-cell function, and worse cardiovascular risk profile and therefore are at
      greater risk of developing T2DM and cardiovascular disease.

PMID- 23539737
TI  - Advanced age influences the dynamic changes in circulating C-reactive protein
      following injury.
AB  - BACKGROUND: The concentration of C-reactive protein (CRP), a biomarker of
      systemic inflammation, is determined by genetic, clinical and demographic factors
      including gender, smoking and body mass index (BMI). The influence of age on CRP
      dynamic changes following insult has, however, been poorly characterised.
      METHODS: We used unilateral hernia repair as a model of standardised insult to
      investigate the influence of baseline demographic and clinico-pathological
      factors affecting the dynamic changes in CRP, interleukin (IL) 6 and tumour
      necrosis factor-alpha over a time course of 48 h following injury. RESULTS: We
      derived CRP negativisation kinetics on 100 prospectively enrolled male subjects
      with mean age of 60.6 years (range 24-90 years) and mean BMI of 25.7 kg/m(2)
      (range 17.9-37 kg/m(2)). Patients who failed to normalise CRP to<10 mg/l at 48 h
      (n=74) were significantly older (p<0.001), had longer surgical times (p=0.05),
      higher waist/hip ratio (p=0.02). Multiple regression analysis confirmed age as
      the only independent predictor of delayed CRP normalisation (p=0.03). Persistent
      CRP elevation was associated with higher peak CRP values (p<0.001), higher IL-6
      concentrations at 24 (p=0.01) and 48 h (p=0.03). CONCLUSIONS: CRP decline
      following insult is delayed in elderly patients as a result of unopposed IL-6
      release. Age should be routinely incorporated in the assessment of CRP response
      to avoid misinterpretation of age-related delay in CRP clearance with ongoing
      systemic inflammation.

PMID- 23539738
TI  - The significance of the senescence pathway in breast cancer progression.
AB  - Invasive breast cancer develops through prolonged accumulation of multiple
      genetic changes. The progression to a malignant phenotype requires overriding of
      growth inhibition. It is evident that some breast cancers have an inherited
      basis, and both hereditary and sporadic cancers appear to involve molecular
      mechanisms that are linked to the cell cycle. Frequently, changes in the
      molecular pathways with gene deletions, point mutations and/or overexpression of
      growth factors can be seen in these cancers. Recent evidence also implicates the
      senescence pathway in breast carcinogenesis. It has a barrier effect towards
      excessive cellular growth, acting as the regulator of tumour initiation and
      progression. Later in carcinogenesis, acquisition of the senescence associated
      secretory phenotype may instead promote tumour progression by stimulating growth
      and transformation in adjacent cells. This two-edge role of senescence in cancer
      directs more investigations into the effects of the senescence pathway in the
      development of malignancy. This review presents the current evidence on the roles
      of senescence molecular pathways in breast cancer and its progression.

PMID- 23539739
TI  - IGFBP-5 overexpression as a poor prognostic factor in patients with urothelial
      carcinomas of upper urinary tracts and urinary bladder.
AB  - BACKGROUND: Urothelial carcinoma (UC) is prevalent worldwide. Dysregulation of
      cell growth is a critical event of tumorigenesis and has not been assessed
      systemically in UC. We thus assessed the published transcriptome of urinary
      bladder urothelial carcinoma (UBUC) and identified insulin-like growth factor
      binding protein-5 (IGFBP-5) as the most significantly upregulated gene associated
      with the regulation of cell growth. Moreover, validated by using public domain
      data set, IGFBP-5 expression also significantly predicted worse outcome. IGFBP-5
      is one of the binding proteins that regulate insulin-like growth factors (IGFs)
      and its significance has not been comprehensively evaluated in UCs. METHODS:
      Using immunohistochemistry, we evaluated the IGFBP-5 expression status and its
      associations with clinicopathological features and survival in 340 cases of upper
      urinary tract urothelial carcinoma (UTUC) and 295 cases of UBUC. Western blot
      analysis was used to evaluate IGFBP-5 protein expression in human urothelial cell
      (HUC) lines. RESULTS: IGFBP-5 overexpression was significantly associated with
      advanced pT stage (p<0.001), high histological grade (UTUC, p<0.001; UBUC,
      p=0.035), lymph node metastasis (UTUC, p=0.006; UBUC, p=0.004), vascular invasion
      (UTUC, p<0.001; UBUC, p=0.003), perineural invasion (UTUC, p=0.034; UBUC,
      p=0.021) and frequent mitosis (UTUC, p<0.001; UBUC, p=0.023). IGFBP-5
      overexpression also independently predicted poor disease-specific survival and
      metastasis-free survival in both groups of patients. Western blot analysis showed
      IGFBP-5 protein as overexpressed in human urothelial cancer cell lines and not in
      normal urothelial cancer cells. CONCLUSIONS: IGFBP-5 plays an important role in
      tumour progression in UC. Its overexpression is associated with advanced tumour
      stage and conferred poorer clinical outcome.

PMID- 23539740
TI  - Clinicopathological significance of HER2/neu genetic heterogeneity in HER2/neu
      non-amplified invasive breast carcinomas and its concurrent axillary metastasis.
AB  - BACKGROUND: HER2/neu (HER2) is a significant prognostic marker for breast
      carcinomas. Recently, new guidelines defining HER2 genetic heterogeneity (GH)
      were published by the College of American Pathologists. AIMS: To determine the
      prevalence of HER2 GH as defined in primary invasive breast carcinoma, to
      determine its relationship with prognostic variables and to investigate its
      impact on concurrent axillary metastasis. METHODS: 235 consecutive infiltrating
      breast carcinomas were evaluated for GH (defined as presence of 5-50% of
      neoplastic cells with HER2/CEP17 ratio >2.2) using fluorescence in situ
      hybridisation. Pathological features of carcinomas with GH were compared with
      those lacking GH. GH was also evaluated in a subset of 37 paired primary
      carcinomas and its concurrent axillary nodal metastases using dual in situ
      hybridisation. RESULTS: HER2 GH was noted in 27% of HER2 negative breast
      carcinomas. These carcinomas demonstrated aggressive characteristics (larger
      size, higher grade and greater incidence of lymph node metastasis) in comparison
      with HER2 negative cases without GH. Higher levels of GH were associated with the
      equivocal HER2 status. GH was maintained in the concurrent lymph node metastases
      with some variations; however, two cases with clusters of HER2 amplified cells in
      the primary carcinoma showed HER2 amplification in the nodal metastasis.
      CONCLUSIONS: HER2 GH is present in 27% of breast carcinomas, portends an
      aggressive phenotype and contributes to the equivocal HER2 status. Evaluation of
      the HER2 status in nodal metastasis of select primary carcinomas with GH may be
      beneficial before treatment selection.

PMID- 23539741
TI  - Ductal carcinoma in situ associated with triple negative invasive breast cancer:
      evidence for a precursor-product relationship.
AB  - AIMS: We evaluated pathological features of the ductal carcinoma in situ
      component of 241 triple negative invasive breast cancers. RESULTS: We found that
      151 (62.6%) in situ lesions were of high nuclear grade, and 236 (97.9%) were
      triple negative (oestrogen receptor, progesterone receptor, cerbB2 negative).
      Immunohistochemistry for cytokeratin (CK)5/6, CK14, CK17, epidermal growth factor
      receptor (EGFR), CD117, 34betaE12, p63 and smooth muscle actin (SMA) revealed
      positive staining in 5 (2.1%), 60 (24.9%), 69 (28.6%), 37 (15.4%), 69 (28.6%),
      137 (56.8%), 3 (1.2%) and 22 (9.1%) in situ ductal components respectively, with
      fair to substantial agreement of staining results (positive versus negative)
      between in situ and corresponding invasive elements for CK5/6, CK14, CK17, EGFR,
      CD117 and 34betaE12; but none to fair agreement for p63 and SMA respectively.
      When the tri-panel of CK14, EGFR and 34betaE12 was used to define the basal
      phenotype, 68% revealed basal-like expression of both in situ and invasive
      components of the same case. CONCLUSIONS: Our data support the notion that triple
      negative ductal carcinoma in situ is the precursor of the corresponding invasive
      counterpart, and that basal-like expression is maintained in the majority of
      invasive cancers associated with basal-like in situ disease. Future studies that
      prospectively evaluate morphological and biological characteristics of invasive
      cancers that develop from triple negative and basal-like ductal carcinoma in situ
      lesions will assist in validating these findings.

PMID- 23539742
TI  - The multiple paths to heteroresistance and intermediate resistance to vancomycin
      in Staphylococcus aureus.

PMID- 23539743
TI  - Microbial translocation induces an intense proinflammatory response in patients
      with visceral leishmaniasis and HIV type 1 coinfection.
AB  - BACKGROUND:  Leishmania infection is a cofactor in the heightened cellular
      activation observed in patients with American visceral leishmaniasis and human
      immunodeficiency virus type 1 (HIV) infection, with or without progression to
      AIDS (AVL/HIV). Thus, the persistence of a high parasite load despite
      antileishmanial therapy could be responsible for the continued immune
      stimulation. METHODS:  CD8(+) T cells expressing CD38, parasite load,
      lipopolysaccharide (LPS), soluble CD14, macrophage migration inhibitory factor
      (MIF), intestinal fatty acid-binding protein (IFABP), and proinflammatory
      cytokines (interleukin 1beta, interleukin 6, interleukin 8, interleukin 17,
      interferon gamma, and tumor necrosis factor) were measured in 17 patients with
      AVL/HIV, 16 with HIV, and 14 healthy subjects (HS). RESULTS:  Lower Leishmania
      parasitemia was observed after antileishmanial and antiretroviral therapies.
      However, higher levels of CD38(+) on CD8(+) T cells were observed in both
      clinical phases of leishmaniasis, compared with HIV cases. AVL/HIV and HIV
      patients showed higher levels of LPS and IFABP than HS. Proinflammatory cytokine
      levels were significantly augmented in patients with active coinfection, as well
      as those with remission of Leishmania infection. LPS levels and Leishmania
      infection were positively correlated with CD38 expression on CD8(+) T cells and
      with IL-6 and IL-8 levels. CONCLUSIONS:  LPS levels along with the immune
      consequences of Leishmania infection were associated with elevated cellular
      activation in coinfected patients. As a consequence, secondary chemoprophylaxis
      for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be
      considered for improving the prognosis of AVL/HIV.

PMID- 23539744
TI  - Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein
      1 and protection from infection with blood-stage parasites.
AB  - BACKGROUND:  Acquired immunity to malaria develops with increasing age and
      repeated infections. Understanding immune correlates of protection from malaria
      would facilitate vaccine development and identification of biomarkers that
      reflect changes in susceptibility resulting from ongoing malaria control efforts.
      METHODS:  The relationship between immunoglobulin G (IgG) antibody and both
      interferon gamma (IFN-gamma) and interleukin 10 (IL-10) responses to the 42-kD C
      terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142)
      and the risk of (re)infection were examined following drug-mediated clearance of
      parasitemia in 94 adults and 95 children in an area of holoendemicity of western
      Kenya. RESULTS:  Positive IFN-gamma enzyme-linked immunosorbent assay (ELISA) and
      enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were
      associated with delayed time to (re)infection, whereas high-titer IgG antibodies
      to MSP142 3D7 or FVO alleles were not independently predictive of the risk of
      (re)infection. When IFN-gamma and IL-10 responses were both present, the
      protective effect of IFN-gamma was abrogated. A Cox proportional hazard model
      including IFN-gamma, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S
      genotype, age, and infection status at baseline showed that the time to blood
      stage infection correlated positively with IFN-gamma responses and negatively
      with IL-10 responses, younger age, and asymptomatic parasitemia. CONCLUSIONS: 
      Evaluating combined allele-specific cellular and humoral immunity elicited by
      malaria provides a more informative measure of protection relative to evaluation
      of either measure alone.

PMID- 23539745
TI  - Alternative mutational pathways to intermediate resistance to vancomycin in
      methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND:  We used 2 in vitro experimental systems to compare phenotypic and
      genotypic changes that accompany selection of mutants of methicillin-resistant
      Staphylococcus aureus (MRSA) strain JH1 with low-level vancomycin resistance
      similar to the type found in vancomycin-intermediate S. aureus (VISA). METHODS: 
      The previously described MRSA strain JH1 and its vancomycin-intermediate mutant
      derivative JH2, both of which were recovered from a patient undergoing vancomycin
      chemotherapy, were used in this study. Mutants of JH1 were selected in vitro by
      means of a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial
      vegetations (SEVs) and by exposure to vancomycin in laboratory growth medium.
      Phenotypic abnormalities of JH1 mutants generated by each in vitro experimental
      system were compared to those of JH2, and whole genomes of 2 in vitro JH1 mutants
      were sequenced to identify mutations that may be associated with an increased
      vancomycin minimum inhibitory concentration. RESULTS:  JH1R1 was selected from
      the PK/PD model, and JH1R2 was selected in laboratory growth medium. Both mutants
      displayed reduced vancomycin and daptomycin susceptibility and phenotypic
      alterations (eg, thicker cell walls and abnormal autolysis) that are typical of
      in vivo VISA mutants. Genome sequencing of JH1R1 identified point mutations in 4
      genes, all of which were different from the mutations described in JH2, including
      1 mutation in yycG, a component of the WalKR sensory regulatory system.
      Sequencing of the JH1R2 genome identified mutations in 7 genes, including 2 in
      rpoB. CONCLUSION:  Our findings indicate that JH1 is able to develop VISA-type
      resistance through several alternative genetic pathways.

PMID- 23539746
TI  - HIV treatments have malaria gametocyte killing and transmission blocking
      activity.
AB  - BACKGROUND:  Millions of individuals being treated for human immunodeficiency
      virus (HIV) live in malaria-endemic areas, but the effects of these treatments on
      malaria transmission are unknown. While drugs like HIV protease inhibitors (PIs)
      and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites
      during liver or asexual blood stages, their effects on transmission stages
      require further study. METHODS:  The HIV PIs lopinavir and saquinavir, the
      nonnucleoside reverse-transcriptase inhibitor nevirapine, and the antibiotic TMP
      SMX were assessed for activity against Plasmodium falciparum transmission stages.
      The alamarBlue assay was used to determine the effects of drugs on gametocyte
      viability, and exflagellation was assessed to determine the effects of drugs on
      gametocyte maturation. The effects of drug on transmission were assessed by
      calculating the mosquito oocyst count as a marker for infectivity, using standard
      membrane feeding assays. RESULTS:  Lopinavir and saquinavir have gametocytocidal
      and transmission blocking activities at or approaching clinically relevant
      treatment levels, while nevirapine does not. TMP-SMX is not gametocytocidal, but
      at prophylactic levels it blocks transmission. CONCLUSIONS:  Specific HIV
      treatments have gametocyte killing and transmission-blocking effects. Clinical
      studies are warranted to evaluate these findings and their potential impact on
      eradication efforts.

PMID- 23539753
TI  - Ovarian cancer among 8,005 women from a breast cancer family history clinic: no
      increased risk of invasive ovarian cancer in families testing negative for BRCA1
      and BRCA2.
AB  - BACKGROUND: Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer
      risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive
      families and if this risk is extended to BRCA negative families. PATIENTS AND
      METHODS: A prospective study involving women seen at a single family history
      clinic in Manchester, UK. Patients were excluded if they had ovarian cancer or
      oophorectomy prior to clinic. Follow-up was censored at the latest date of:
      31/12/2010; ovarian cancer diagnosis; oophorectomy; or death. We used person
      years at risk to assess ovarian cancer rates in the study population, subdivided
      by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the
      general population. RESULTS: We studied 8005 women from 895 families. Women from
      BRCA2 mutation families showed a 17-fold increased risk of invasive ovarian
      cancer (relative risk (RR) 16.67; 95% CI 5.41 to 38.89). This risk increased to
      50-fold in women from families with BRCA1 mutations (RR 50.00; 95% CI 26.62 to
      85.50). No association was found for women in families tested negative for
      BRCA1/2, where there was 1 observed invasive ovarian cancer in 1613 women when
      2.74 were expected (RR 0.37; 95% CI 0.01 to 2.03). There was no association with
      ovarian cancer in families untested for BRCA1/2 (RR 0.99; 95% CI 0.45 to 1.88).
      DISCUSSION: This study showed no increased risk of ovarian cancer in families
      that tested negative for BRCA1/2 or were untested. These data help counselling
      women from BRCA1/2 negative families with breast cancer that their risk of
      invasive ovarian cancer is not higher than the general population.

PMID- 23539754
TI  - Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic
      kidney disease in Japanese individuals by a genome-wide association study.
AB  - BACKGROUND: Although genome-wide association studies (GWASs) have implicated
      several genes in the predisposition to chronic kidney disease (CKD) in Caucasian
      or African American populations, the genes that confer susceptibility to CKD in
      Asian populations remain to be identified definitively. We performed a GWAS to
      identify genetic variants that confer susceptibility to CKD in Japanese
      individuals. METHODS: 3851 Japanese individuals from three independent subject
      panels were examined. Subject panels A, B, and C comprised 252, 910, and 190
      individuals with CKD and 249, 838, and 1412 controls, respectively. A GWAS for
      CKD was performed in subject panel A. RESULTS: Five single nucleotide
      polymorphisms (SNPs) at chromosome 3q28, ALPK1, FAM78B, and UMODL1 were
      significantly (false discovery rate<0.05) associated with CKD by the GWAS. The
      relation of these five SNPs and of an additional 22 SNPs at these loci to CKD was
      examined in subject panel B, revealing that rs9846911 at 3q28 was significantly
      associated with CKD in all individuals and that rs2074381 and rs2074380 in ALPK1
      were associated with CKD in individuals with diabetes mellitus. These three SNPs
      were further examined in subject panel C, revealing that rs2074381 and rs2074380
      were significantly associated with CKD. For subject panels B and C combined,
      rs9846911 was significantly associated with CKD in all individuals and rs2074381
      and rs2074380 were associated with CKD in diabetic individuals. CONCLUSIONS:
      Chromosome 3q28 may be a susceptibility locus for CKD in Japanese individuals,
      and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes
      mellitus.

PMID- 23539755
TI  - Disparities in ovarian cancer care quality and survival according to race and
      socioeconomic status.
AB  - BACKGROUND: The relationship between racial and socioeconomic status (SES)
      disparities and the quality of epithelial ovarian cancer care and survival
      outcome are unclear. METHODS: A population-based analysis of National Cancer Data
      Base (NCDB) records for invasive primary epithelial ovarian cancer diagnosed in
      the period from 1998 to 2002 was done using data from patients classified as
      white or black. Adherence to National Comprehensive Cancer Network (NCCN)
      guideline care was defined by stage-appropriate surgical procedures and
      recommended chemotherapy. The main outcome measures were differences in adherence
      to NCCN guidelines and overall survival according to race and SES and were
      analyzed using binomial logistic regression and multilevel survival analysis.
      RESULTS: A total of 47 160 patients (white = 43 995; black = 3165) were
      identified. Non-NCCN-guideline-adherent care was an independent predictor of
      inferior overall survival (hazard ratio [HR] = 1.43, 95% confidence interval [CI]
      = 1.38 to 1.47). Demographic characteristics independently associated with a
      higher likelihood of not receiving NCCN guideline-adherent care were black race
      (odds ratio [OR] = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR =
      1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI =
      1.19 to 1.49). After controlling for disease and treatment-related variables,
      independent racial and SES predictors of survival were black race (HR = 1.29, 95%
      CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not
      insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household
      income less than $35 000 (HR = 1.06, 95% CI = 1.02 to 1.11). CONCLUSIONS: These
      data highlight statistically and clinically significant disparities in the
      quality of ovarian cancer care and overall survival, independent of NCCN
      guidelines, along racial and SES parameters. Increased efforts are needed to more
      precisely define the patient, provider, health-care system, and societal factors
      leading to these observed disparities and guide targeted interventions.

PMID- 23539756
TI  - Impact of early parenteral nutrition on metabolism and kidney injury.
AB  - A poor nutritional state and a caloric deficit associate with increased morbidity
      and mortality, but a recent multicenter, randomized controlled trial found that
      early parenteral nutrition to supplement insufficient enteral nutrition increases
      morbidity in the intensive care unit, including prolonging the duration of renal
      replacement therapy, compared with withholding parenteral nutrition for 1 week.
      Whether early versus late parenteral nutrition impacts the incidence and recovery
      of AKI is unknown. Here, we report a prespecified analysis from this trial, the
      Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill
      Patients (EPaNIC) study. The timing of parenteral nutrition did not affect the
      incidence of AKI, but early initiation seemed to slow renal recovery in patients
      with stage 2 AKI. Early parenteral nutrition did not affect the time course of
      creatinine and creatinine clearance but did increase plasma urea, urea/creatinine
      ratio, and nitrogen excretion beginning on the first day of amino acid infusion.
      In the group that received late parenteral nutrition, infusing amino acids after
      the first week also increased ureagenesis. During the first 2 weeks, ureagenesis
      resulted in net waste of 63% of the extra nitrogen intake from early parenteral
      nutrition. In conclusion, early parenteral nutrition does not seem to impact AKI
      incidence, although it may delay recovery in patients with stage 2 AKI.
      Substantial catabolism of the extra amino acids, which leads to higher levels of
      plasma urea, might explain the prolonged duration of renal replacement therapy
      observed with early parenteral nutrition.

PMID- 23539757
TI  - Kielin/chordin-like protein attenuates both acute and chronic renal injury.
AB  - The secreted kielin/chordin-like (KCP) protein, one of a family of cysteine-rich
      proteins, suppresses TGF-beta signaling by sequestering the ligand from its
      receptor, but it enhances bone morphogenetic protein (BMP) signaling by promoting
      ligand-receptor interactions. Given the critical roles for TGF-beta and BMP
      proteins in enhancing or suppressing renal interstitial fibrosis, respectively,
      we examined whether secreted KCP could attenuate renal fibrosis in mouse models
      of chronic and acute disease. Transgenic mice that express KCP in adult kidneys
      showed significantly less expression of collagen IV, alpha-smooth muscle actin,
      and other markers of disease progression in the unilateral ureteral obstruction
      model of renal interstitial fibrosis. In the folic acid nephrotoxicity model of
      acute tubular necrosis, mice expressing KCP survived high doses of folic acid
      that were lethal for wild-type mice. With a lower dose of folic acid, mice
      expressing KCP exhibited improved renal recovery compared with wild-type mice.
      Thus, these data suggest that extracellular regulation of the TGF-beta/BMP
      signaling axis by KCP, and by extension possibly other cysteine-rich domain
      proteins, can attenuate both acute and chronic renal injury.

PMID- 23539758
TI  - Vitamin D status and outcomes after renal transplantation.
AB  - Kidney transplant recipients usually have low vitamin D levels, especially in the
      early posttransplantation period, but the association between vitamin D status
      with renal outcomes is not well described in this population. Here, we studied a
      prospective cohort of 634 kidney recipients who underwent transplantation at a
      single institution between January 2005 and June 2010. In this cohort, low 25
      hydroxyvitamin D concentrations 3 months after transplantation did not predict
      early death or graft loss but were independently associated with lower measured
      GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular
      atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol,
      parathyroid hormone, or fibroblast growth factor-23 were not consistently
      associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin
      D concentration measured 3 months after transplantation is an independent risk
      factor for interstitial fibrosis progression and is associated with a lower GFR 1
      year after transplantation.

PMID- 23539759
TI  - MICA variant promotes allosensitization after kidney transplantation.
AB  - MHC class I-related chain A (MICA) antigens are surface glycoproteins strongly
      implicated in innate immunity, and the MICA gene is highly polymorphic. Clinical
      observations suggest a role for donor MICA antigens expressed on transplant
      endothelial cells in the alloimmune response, but the effect of MICA genotype is
      not well understood. Here, we investigated the immunologic effect of the A5.1
      mutation, related to the common MICA*008 allele. Compared with wild-type
      endothelial cells (ECs), homozygosity for MICA A5.1 associated with an
      endothelial phenotype characterized by 7- to 10-fold higher levels of MICA mRNA
      and MICA proteins at the cell surface, as well as exclusive release in exosomes
      instead of enzymatic cleavage. Mechanistically, we did not detect quantitative
      changes in regulatory microRNAs. Functionally, A5.1 ECs enhanced NKG2D
      interaction and natural killer cell activation, promoting NKG2D-dependent lysis
      of ECs. In kidney transplant recipients, polyreactive anti-MICA sera bound
      preferentially to ECs from MICA A5.1 donors, suggesting that MICA*008(A5.1)
      molecules are the preferential antigenic determinants on ECs of grafts.
      Furthermore, the incidence of MICA A5.1 mismatch revealed a statistically
      significant association between donor MICA A5.1 and both anti-MICA sensitization
      and increased proteinuria in kidney recipients. Taken together, these results
      identify the A5.1 mutation as an immunodominant factor and a potential risk
      factor for transplant survival.

PMID- 23539760
TI  - Podocytes are nonhematopoietic professional antigen-presenting cells.
AB  - Podocytes are essential to the structure and function of the glomerular
      filtration barrier; however, they also exhibit increased expression of MHC class
      II molecules under inflammatory conditions, and they remove Ig and immune
      complexes from the glomerular basement membrane (GBM). This finding suggests that
      podocytes may act as antigen-presenting cells, taking up and processing antigens
      to initiate specific T cell responses, similar to professional hematopoietic
      cells such as dendritic cells or macrophages. Here, MHC-antigen complexes
      expressed exclusively on podocytes of transgenic mice were sufficient to activate
      CD8+ T cells in vivo. In addition, deleting MHC class II exclusively on podocytes
      prevented the induction of experimental anti-GBM nephritis. Podocytes ingested
      soluble and particulate antigens, activated CD4+ T cells, and crosspresented
      exogenous antigen on MHC class I molecules to CD8+ T cells. In conclusion,
      podocytes participate in the antigen-specific activation of adaptive immune
      responses, providing a potential target for immunotherapies of inflammatory
      kidney diseases and transplant rejection.

PMID- 23539762
TI  - Parathyroid imaging: the importance of pinhole collimation with both single- and
      dual-tracer acquisition.
AB  - Our objective was to rigorously compare pinhole and parallel-hole collimation in
      an intrapatient, intrastudy design in 2 parathyroid imaging protocols: the first
      was dual-phase (99m)Tc-sestamibi imaging, and the second was dual-phase (99m)Tc
      sestamibi plus dual-tracer ((99m)Tc-sestamibi and (123)I) simultaneous
      acquisition subtraction imaging. METHODS: Thirty-three patients with 37
      surgically proven nonectopic parathyroid adenomas were evaluated. Anterior
      pinhole and parallel-hole images of the neck were available for (99m)Tc-sestamibi
      at 15 min and 3 h, and for simultaneously acquired (99m)Tc-sestamibi and (123)I
      subtraction at 15 min, all from a single study. The images were modified so that
      all had a square border and so that the thyroid filled approximately three
      quarters of the image. The images were evaluated by 2 experienced nuclear
      medicine physicians who did not know the surgical results or whether the images
      were acquired with pinhole or parallel-hole collimation. The observers indicated
      the location of any identified adenoma and graded the certainty of diagnosis on a
      3-point scale. RESULTS: The localization success rate for the 2 observers
      combined for the single-tracer dual-phase images was 66.2% with pinhole
      collimation and 43.2% with parallel-hole collimation (P < 0.0001). The
      localization success rate with the addition of the dual-tracer simultaneous
      acquisition subtraction image was 83.8% with pinhole collimation and 62.2% with
      parallel-hole collimation (P = 0.0018). In addition, the degree of certainty of
      localization was greater with pinhole collimation with both imaging protocols (P
      < 0.001 in both cases). CONCLUSION: In the anterior projection, pinhole
      collimation is superior to parallel-hole collimation for parathyroid imaging with
      either dual-phase (99m)Tc-sestamibi or dual-phase (99m)Tc-sestamibi plus dual
      tracer ((99m)Tc-sestamibi and (123)I) simultaneous-acquisition subtraction.

PMID- 23539763
TI  - National Outstanding Clinician Scientist Award 2012: Pierce Chow.

PMID- 23539761
TI  - Epithelial cell TGFbeta signaling induces acute tubular injury and interstitial
      inflammation.
AB  - TGFbeta signaling plays a central role in the development of acute and chronic
      kidney diseases. Previous in vivo studies involved systemic alteration of TGFbeta
      signaling, however, limiting conclusions about the direct role of TGFbeta in
      tubular cell injury. Here, we generated a double transgenic mouse that inducibly
      expresses a ligand-independent constitutively active TGFbeta receptor type 1
      (TbetaR1) kinase specifically in tubular epithelial cells, with expression
      restricted by the Pax8 promoter. In this model, activation of TGFbeta signaling
      in the tubular epithelium alone was sufficient to cause AKI characterized by
      marked tubular cell apoptosis and necrosis, oxidative stress, dedifferentiation
      and regenerative cell proliferation, reduced renal function, and interstitial
      accumulation of inflammatory cells. This tubular injury was associated with
      mitochondrial-derived generation of reactive oxygen species (ROS), but cell
      damage and apoptosis were partially independent of mitochondrial-derived ROS.
      TbetaR1 signaling-induced tubular injury also associated with significant
      leukocyte infiltration consisting of F4/80(+) macrophages, CD11c(+) F4/80(+)
      dendritic cells, CD11c(+) F4/80(-) Ly6C(high) dendritic cells/monocytes, and T
      cells. Inhibition of mitochondrial-derived ROS significantly reduced accumulation
      of CD11c(+) F4/80(+) dendritic cells and T cells, suggesting a role for ROS in
      the activation and recruitment of the adaptive immune response to tubular injury.
      Taken together, these results suggest that TGFbeta signaling in the tubular
      epithelium alone is sufficient to cause acute tubular injury and inflammation;
      therefore, TGFbeta may be a mechanistic link between acute injury and chronic
      progression of kidney disease.

PMID- 23539764
TI  - Fluoroscopy guided cervical interlaminar steroid injections in patients with
      cervical pain syndromes: a retrospective study.
AB  - OBJECTIVE: The objective of this retrospective study was to examine the efficacy
      of fluoroscopically guided cervical interlaminar epidural steroid injections
      (CILESI). MATERIALS AND METHODS: Sixty-five patients who received their first
      fluoroscopically guided CILESI over a 12 month interval were retrospectively
      identified. Patients who had failed conservative non-surgical management and
      patients who were otherwise candidates of surgery were included in this trial of
      CILESI. The verbal numerical rating scales (VNRS) before the treatment, within
      one hour after the treatment, and upon follow-up, were analyzed. RESULTS: The
      most preferred intervention level of CILESI was C5-C6. There was a statistically
      significant improvement in the VNRS scores from before the injection to
      immediately after the injection, and upon follow-up. Fifty-one patients (80%) had
      perfect/good scores. No major complications were encountered after CILESI, but
      one patient (1.54%) had a vasovagal reaction and another patient (1.54%) had a
      transient increase of pain after injection. CONCLUSION: Fluoroscopy guided CILESI
      is a safe and an effective treatment for patients with cervical pain syndromes.
      The success rates show that a large percentage of the patients may obtain relief
      from radicular symptoms and avoid surgery for the follow-up period up to 12
      months.

PMID- 23539765
TI  - One-year-survey with multicenter data of more than 4,500 patients with
      degenerative rheumatic diseases treated with therapeutic nuclear magnetic
      resonance.
AB  - BACKGROUND AND OBJECTIVES: Nuclear magnetic resonance (NMR) has been shown to
      stimulate repair processes and cartilage and to influence pain signalling. It
      represents an alternative therapy for patients suffering from osteoarthritis
      (OA). To prove the clinical success of this new therapeutical method, validated
      measuring parameters are important that are convincing for pain and function in a
      one-year-follow-up. METHODS: During the course of its application over the last
      10 years, over 4,500 protocols of a one-year-follow-up have been collected to
      record the outcome of NMR therapy. This report reflects the outcome of NMR
      therapy on patients with the following degenerative rheumatic diseases: OA of the
      knee (n = 2.770), OA of the hip (n = 673), OA of the ankle joint (n = 420) and
      chronic low back pain (n = 655). Data were collected at baseline, 6-8 weeks and 6
      and 12 months following NMR treatment. RESULTS: Pain was reduced significantly 6
      weeks after NMR treatment in the cases of all four examined indications and
      stayed measurably reduced up to 6 and 12 months. The improvements in all three
      forms of pain (pain on load, pain on motion, pain at rest) following NMR
      treatment were around 21-50% on average. CONCLUSIONS: Following therapy with NMR,
      patients with OA of all four types experienced a distinct improvement in their
      ability in functional parameters. Overall, the 10 years of a one-year-survey with
      multicenter data gathered on the effect of NMR therapy on patients verifiably
      proved its efficacy amongst patients with degenerative rheumatic diseases.

PMID- 23539766
TI  - Hypermethylation of the MTHFR gene is common in sperm from couples with
      unexplained pregnancy loss.

PMID- 23539767
TI  - Aberrant methylation of the H19 imprinting control region may increase the risk
      of spontaneous abortion.

PMID- 23539768
TI  - [Paper of the Month # 36 - Swiss patient safety].

PMID- 23539769
TI  - Value-based insurance design yields near- and long-term improvements in
      medication adherence.
AB  - Key findings. (1) Value-based insurance design (VBID) improves medication
      adherence by 1 to 3 percent in the first year after implementation; (2)
      Improvements in adherence were sustained and amplified in the second year post
      implementation, ranging from 2 to 5 percent; (3) Adherence improvements varied ac
      cording to VBID participants' baseline adherence, with greatest improve-ments
      evident in those with poorer baseline adherence

PMID- 23539770
TI  - Advancing occupation-based practice: interpreting the rhetoric.

PMID- 23539771
TI  - Age effects on sensory-processing abilities and their impact on handwriting.
AB  - BACKGROUND: Sensory-processing abilities are known to deteriorate in the elderly.
      As a result, daily activities such as handwriting may be impaired. Yet, knowledge
      about sensory-processing involvement in handwriting characteristics among older
      persons is limited. PURPOSE: To examine how age influences sensory-processing
      abilities and the impact on handwriting as a daily performance. METHOD: The study
      participants were 118 healthy, independently functioning adults divided into four
      age groups: 31-45, 46-60, 61-75 and 76+ years. All participants completed the
      Adolescent/ Adult Sensory Profile (AASP). Handwriting process was documented
      using the Computerized Handwriting Penmanship Evaluation Tool (ComPET). FINDINGS:
      Age significantly affects sensory processing and handwriting pressure as well as
      temporal and spatial measures. Both handwriting time and spatial organization of
      the written product were predicted by sensory seeking. When examining age
      contribution to the prediction of handwriting by sensory processing, sensory
      seeking showed a tendency for predicting handwriting pressure (p = .06), while
      sensory sensitivity significantly predicted handwriting velocity. IMPLICATIONS:
      Age appears to influence sensory-processing abilities and affect daily
      performance tasks, such as handwriting, for which sensitivity and seeking for
      sensations are essential. Awareness of clinicians to sensory-processing deficits
      among older adults and examining their impact on broader daily activities are
      essential to improve daily performance and quality of life.

PMID- 23539772
TI  - Professionalism and occupational therapy: an exploration of faculty and students'
      perspectives.
AB  - BACKGROUND: Professionalism is a complex, multifaceted concept embedded within
      the curricula of occupational therapy programs and professional documents; yet
      there is no clear explanation in the literature. PURPOSE: To explore occupational
      therapy faculty and students' perspectives of the meaning of professionalism.
      METHODS: This interpretivist qualitative study used convenience sampling to
      recruit eight second-year occupational therapy master's students and five
      occupational therapy faculty members to participate in two separate focus groups.
      Open-coding and constant comparative methods were used to identify themes.
      FINDINGS: Data analysis yielded the following student focus group themes:
      uncertainty about professional expectations; searching for answers through
      concrete concepts; and the context-specific nature of professionalism. Faculty
      focus group themes were professional responsibility; professional awareness; and
      the context-specific nature of professionalism. Understanding and enacting
      professionalism may be a developmental process. IMPLICATIONS: Further exploration
      of the meaning of professionalism from a variety of other occupational therapy
      stakeholders is needed.

PMID- 23539773
TI  - The practice experience of evangelical Christian occupational therapists.
AB  - BACKGROUND: Occupational therapists who are religious are more likely to address
      spirituality in practice; however, little is known regarding the practice
      experience of therapists who hold particular faith perspectives. PURPOSE: To
      examine the practice experience of evangelical Christian occupational therapists
      in the context of professional emphasis on spirituality as a largely secular
      domain of practice. METHODS: . A qualitative, interpretivist approach was used
      for this study. Seven evangelical Christian occupational therapists were engaged
      in in-depth interviews; verbatim transcripts were thematically coded. FINDINGS:
      Christianity was viewed as a practice resource through the use of private prayer
      and Christian values to support compassionate practice. Evangelical Christian
      occupational therapists navigated the tensions of working in a secular healthcare
      system through awareness of work environment and client cues, restrained
      expression of faith, as well as the experience of increased scrutiny for
      potential boundary violations. IMPLICATIONS: Evangelical Christian therapists may
      struggle with secular interpretations of spirituality in practice. Yet they may
      also display heightened awareness concerning potential boundary violations.

PMID- 23539774
TI  - Learning together for effective collaboration in school-based occupational
      therapy practice.
AB  - BACKGROUND: School-based occupational therapy (SBOT) practice takes place within
      a complex system that includes service recipients, service providers, and program
      decision makers across health and education sectors. Despite the promotion of
      collaborative consultation at a policy level, there is little practical guidance
      about how to coordinate multi-agency service and interprofessional collaboration
      among these stakeholders. PURPOSE: This paper reports on a process used to engage
      program administrators in an examination of SBOT collaborative consultation
      practice in one region of Ontario to provide an evidence-informed foundation for
      decision making about implementation of these services. METHODS: Within an
      appreciative inquiry framework (Cooperrider, Whitney, & Stavros, 2008),
      Developmental Work Research methods (Engestrom, 2000) were used to facilitate
      shared learning for improved SBOT collaborative consultation. Program
      administrators participated alongside program providers and service recipients in
      a series of facilitated workshops to develop principles that will guide future
      planning and decision making about the delivery of SBOT services. FINDINGS:
      Facilitated discussion among stakeholders led to the articulation of 12
      principles for effective collaborative practice. Program administrators used
      their shared understanding to propose a new model for delivering SBOT services.
      IMPLICATIONS: Horizontal and vertical learning across agency and professional
      boundaries led to the development of powerful solutions for program improvement.

PMID- 23539775
TI  - Measurement properties of the MacHANd performance assessment: a pilot study.
AB  - BACKGROUND: There is a need for a standardized, performance-based hand function
      assessment with strong psychometric properties to evaluate persons following a
      traumatic hand injury. PURPOSE: To conduct a preliminary investigation of the
      reliability and validity of the MacHANd performance assessment (MPA), a new
      standardized hand function test. METHODS: Forty-one people receiving treatment
      for hand injuries were evaluated using the MPA, Patient-rated Wrist and Hand
      Evaluation, and Jebsen-Taylor Hand Function Test. RESULTS: The MPA demonstrated
      adequate inter-rater reliability and excellent test-retest reliability, and it
      confirmed three validation hypotheses. IMPLICATIONS: This pilot study suggests
      that the MPA has good psychometric properties when used with individuals
      following a hand injury; however more research is needed.

PMID- 23539776
TI  - Exploring occupational justice in consumer perspectives on assistive technology.
AB  - BACKGROUND: Occupational justice is an emerging paradigm in the provision of
      occupational therapy services. Assistive technology (AT) services, a key practice
      domain in occupational therapy, facilitate the participation of individuals with
      disabilities in all major occupations. PURPOSE: The goal of this study was to
      explore personal meanings of occupational justice among consumers of AT and to
      propose strategies that integrate values of occupational justice in AT services.
      METHODS: A content analysis of interviews with seven consumers of AT devices was
      employed. Themes relevant to the four conceptual definitions of occupational
      injustice, namely marginalization, alienation, deprivation, and imbalance, were
      identified. FINDINGS: Four corresponding themes were inherent in the consumer
      experiences: ability to exercise choices through use of AT devices, using AT to
      achieve optimum occupational potential, empowerment through AT services, and
      personal relation to the AT device. Specific issues within these themes are
      classified and described according to the four conceptual definitions of
      occupational justice. IMPLICATIONS: The application of occupational justice is
      essential to promote client-centred AT services particularly in evaluation of
      needs, selection and acquisition of AT devices, and training and support for use
      of AT devices.

PMID- 23539777
TI  - The spies above your backyard.

PMID- 23539779
TI  - Unraveling a magellanic mystery.

PMID- 23539778
TI  - The people's standoff.

PMID- 23539780
TI  - Medieval and modern.

PMID- 23539781
TI  - Of lust and lysol.

PMID- 23539782
TI  - Extremely high and incredibly cold.

PMID- 23539783
TI  - Let the sunshine in.

PMID- 23539784
TI  - Good vibrations.

PMID- 23539785
TI  - Shock to the system.

PMID- 23539786
TI  - Disappointment of dazzling displays.

PMID- 23539787
TI  - Ghostly beacons of new physics.

PMID- 23539788
TI  - The neutrino's secrets, written on the sky.

PMID- 23539789
TI  - The future of medicine.

PMID- 23539790
TI  - The true cost of fossil fuels.

PMID- 23539791
TI  - Anguish of the abandoned child.

PMID- 23539792
TI  - The low-cost ticket to space.

PMID- 23539793
TI  - Let the fish breathe.

PMID- 23539794
TI  - Love among the dinosaurs.

PMID- 23539795
TI  - Proof of hallucination.

PMID- 23539796
TI  - Deep heat threatens marine life.

PMID- 23539797
TI  - Alternative dialysis therapies.

PMID- 23539798
TI  - We can do better: by changing culture to improve care.

PMID- 23539799
TI  - Alternative dialysis therapies--why all the interest?
AB  - Alternative dialysis therapies offer options for improving the dialysis care and
      lives of patients. This article reviews the available therapies and presents
      patient-related reasons for offering these therapies. It is through these
      therapies that we can make a positive difference for patients.

PMID- 23539800
TI  - Supporting and retaining nephrology nurses new to the peritoneal dialysis
      specialty.
AB  - The use of home dialysis treatment modalities, including peritoneal dialysis, is
      increasing. To have a successful peritoneal dialysis program, organizations must
      recognize the special abilities required of the nurse practicing in the
      peritoneal dialysis specialty. This article identifies strategies that can be
      used to educate, develop, and retain these nurses.

PMID- 23539801
TI  - Who should be teaching patients to self-cannulate?
AB  - When teaching self-cannulation, a number of variables come into play, beyond
      whether patients have the dexterity or visual acuity to perform the task. To
      solidify learning, such as self-cannulation, it is imperative for nurses to know
      how to teach adult learners, identify each patient's learning style, and possess
      cannulation expertise. Cannulation is an invasive procedure, and it is a very
      personal and emotional learning experience that requires a knowledgeable,
      experienced educator.

PMID- 23539802
TI  - First exposure to home therapy options--where, when, and how.
AB  - Pre-dialysis education is known to impact modality choice among patients with end
      stage renal disease, but many of these patients report a lack of education in
      alternative dialysis therapies. Since 2004, Satellite Healthcare, a non-profit
      dialysis provider, has implemented chronic kidney disease education through
      Options classes at WellBound Centers, resulting in 23% of patients being treated
      with home therapies. The Satellite Healthcare-WellBound experience confirms that
      Options classes and a compelling infrastructure for home dialysis therapies are
      vital elements to bring alternative dialysis therapies to more patients.

PMID- 23539803
TI  - Self cannulation for home hemodialysis: strategies for success.
AB  - Self-cannulation is a technique that allows patients on hemodialysis to place the
      needles into their own vascular access, a fistula, or graft for the purpose of
      hemodialysis. This practice helps to empower individuals having to undergo
      hemodialysis with the opportunity to be active participants in their own care. It
      also reduces anxiety of needles and increases familiarity of the vascular access,
      thereby reducing the risk of infiltration and infection because only one person
      is performing the cannulation.

PMID- 23539804
TI  - Exploring the reasons for the tiny percentage of patients on home hemodialysis.
AB  - The number of patients requiring renal replacement therapy continues to grow.
      When patients are told they need a life-sustaining treatment, it is a profound
      experience that impacts all aspects of their lives and the lives of their
      families. In the United States, the stark reality is the majority of patients are
      treated with in-center hemodialysis, and only a very small percentage with a home
      dialysis therapy, such as peritoneal dialysis or home hemodialysis. Why is this?
      Do patients not factor in preference, independence, or quality and maintenance of
      a normal life? Or is it that as a renal community, nephrology nurses do not
      expose patients to the knowledge they need and promote involvement in this
      decision-making? Is patient autonomy being fostered? This article explores the
      reasons for the tiny percentage of patients on home dialysis and suggests
      strategies to address the education needed, the dynamics of why patients decide
      on a therapy, patient selection characteristics, and myths of who is and is not a
      candidate.

PMID- 23539805
TI  - Perspectives and experiences of a nephrology nurse on home hemodialysis.

PMID- 23539806
TI  - Home dialysis: burden of care.

PMID- 23539807
TI  - What's in a word--caregiver or care partner?

PMID- 23539808
TI  - Best available evidence for peritoneal dialysis catheter exit-site care.

PMID- 23539809
TI  - [Nephrology between economy and ecology].

PMID- 23539810
TI  - [Infectious peritonitis in peritoneal dialysis: an over-emphasized complication].
AB  - Peritoneal dialysis is an extrarenal epuration modality which uses physiological
      properties of peritoneum as a dialysis membrane. Despite the improvement of
      peritoneal dialysis techniques in the last ten years, peritonitis remains one of
      the most redoubt complications. Peritonitis may sometimes lead to technical
      failures, which need catheter removing, but rarely lead to death. Our
      retrospective study at the dialysis center of CHUV has analyzed factors which can
      predict this kind of complication. It calculates peritonitis rate and median
      peritonitis free-survival for different groups of patients. It also describes
      causatives organisms and their sensitivity to antibiotics.

PMID- 23539811
TI  - [Vascular calcifications and vitamin K deficiency: a modifiable risk factor in
      chronic kidney disease].
AB  - The mechanisms of vascular calcifications in chronic renal failure are complex.
      Apart for clotting factors, vitamin K-dependent proteins include matrix Gla
      protein. Glutamic acid residues in matrix Gla protein are carboxylated by vitamin
      K-dependent gamma-carboxylase, which enables it to inhibit calcification. The
      purpose of this review is to discuss available evidence implicating vitamin K as
      a modifiable risk factor in the pathogenesis of vascular calcification in renal
      diseases.

PMID- 23539812
TI  - [Renal stone disease: collaborative management between primary care and
      specialized physicians].
AB  - Nephrolithiasis is a highly prevalent pathology with a 10% lifetime risk in the
      Western population. Although it is often minimized and qualified as "idiopathic"
      significant comorbidities are frequently observed, e.g. the metabolic syndrome,
      type 2 diabetes mellitus, hypertension and bone fragility. Therefore
      nephrolithiasis can be regarded as a systemic disorder. A specialized diagnostic
      and therapeutic approach should be offered to such patients with active kidney
      stone disease in order to prevent stone recurrence and favor early diagnosis of
      said comorbidities.

PMID- 23539813
TI  - [Management of renal anemia in 2013].
AB  - Anemia occurs frequently in patients with chronic kidney disease (CKD),
      especially in the later stages, and the main etiologies are decreased production
      of erythropoietin (EPO) as well as iron and vitamin deficiencies. For these
      reasons, it is essential to detect anemia in patients with CKD and to investigate
      the etiology. If anemia (Hb < 100 g/l) persists after substitution of
      deficiencies, treatment with recombinant human erythropoietin (rHuEPO) should be
      considered. New guidelines (KDIGO - August 2012) have just been published by the
      National Kidney Foundation (NKF) for the management of anemia in patients with
      renal failure. This article reviews the principles and innovations in management
      in 2013.

PMID- 23539814
TI  - [Dialysis and ecology: can we do better in the future?].
AB  - Development of dialysis has saved the lives of many patients. However,
      haemodialysis and peritoneal dialysis are very demanding in resources such as
      water and electricity, and generate a large amount of waste. In this article, we
      will review the environmental aspects of dialysis. Different solutions will be
      discussed, such as recycling of water discharged during reverse osmosis, the
      integration of solar energy, recycling of waste plastics, and the use of other
      techniques such as sorbent dialysis. In a world where natural resources are
      precious and where global warming is a major problem, it is important that not
      only dialysis, but all branches of medicine become more attentive to ecology.

PMID- 23539815
TI  - [The cardiorenal syndrome in 2013: definition, mechanisms and new possible
      treatments].
AB  - The cardiorenal syndrome refers to a group of conditions resulting in cardiac and
      renal dysfunctions. The mechanisms contributing to this syndrome depend on which
      organ is primarily affected. Even if the correction of a potential underlying
      cause is the first therapeutic step, appropriate fluid management is nonetheless
      essential. Both diuretics and ultrafiltration strategies are discussed and new
      possible treatments are mentioned.

PMID- 23539816
TI  - [Case-based practice with ECG in the elderly. Case number 21].

PMID- 23539817
TI  - [Cardiac insufficiency, cerebrovascular accidents and coronary disease: new
      enlightening].

PMID- 23539818
TI  - [Acceleration].

PMID- 23539819
TI  - ["Sedation in terminal care", a french exception?].

PMID- 23539820
TI  - [Dr. House's last diagnostics].

PMID- 23539821
TI  - [Animals and lasagna: all the beastly truth].

PMID- 23539822
TI  - Pure pretense. Are your engine company medics just for show?

PMID- 23539823
TI  - Presumptuous assumptions. What should you choose to believe?

PMID- 23539824
TI  - Outbreak hotel. When flu floods a community, where can a sick patient go?

PMID- 23539825
TI  - Abdominal pain relief. Analgesia won't interfere with docs' diagnoses.

PMID- 23539826
TI  - The quest for a safer ride. From the government to the grass roots, there are
      efforts to improve our vehicles.

PMID- 23539827
TI  - Ambulance safety measures prove their worth. Model vehicles are cheaper to run
      and seem safer for crews.

PMID- 23539828
TI  - Exploring chronic kidney disease. Acute vs. chronic failure and dialysis: what
      EMS should know.

PMID- 23539829
TI  - Transition topics for the paramedic. Part 1: Research: evidence-based decision
      making in EMS.

PMID- 23539830
TI  - Preacher of habit. Avoid mistakes by sticking to the tried-and-true.

PMID- 23539831
TI  - The role of electronic assessment of adherence in the education and counseling of
      children taking growth hormone: progress and challenges.
AB  - There are numerous issues surrounding adherence in children taking recombinant
      human growth hormone (rh-GH). New technologies capable of accurately
      recording/monitoring may highlight some of these issues, and have value in
      optimizing adherence levels through education and counseling. The intention of
      this review is to guide healthcare professionals (HCPs). PubMed, Google Scholar
      and citations in published papers were used to substantiate the views expressed
      by the authors. Both perceptional and practical factors influence the adherence
      levels of children taking rh-GH. Understanding such factors may help to identify
      the characteristics of ideal rh-GH devices and their potential impact on
      adherence. New technologies, such as electronic monitors, may facilitate patient
      provider discussions on adherence, and help identify barriers that are amenable
      to change. Monitoring adherence may also help differentiate nonadherence from
      biological low response to rh-GH therapy. However, the medical, psychological,
      social and ethical aspects of electronic assessment require further
      investigation.

PMID- 23539832
TI  - Cognitive and psychosocial development concerns in children born small for
      gestational age.
AB  - Outcome information for infants born small for gestational age (SGA), whether
      term or premature, suggests poorer cognitive function compared with appropriate
      size for gestational age (AGA) infants. Poorer outcome is associated with smaller
      size for gestational age and with lack of catch-up growth after birth. Such data
      have been reported from early childhood to young adulthood. Diminished head
      circumference at birth and growth thereafter has also been associated with poor
      outcome. Based on available reports, the impact of SGA birth upon psychosocial
      development remains unclear. While it has not been shown that growth hormone (GH)
      therapy impacts either cognitive or psychosocial outcome, increased head
      circumference standard deviation scores have been shown to occur with GH therapy.
      These data need to be interpreted with caution since study populations do not
      define etiology of SGA and definitions of SGA vary. Further, generalized group
      data are not applicable to individuals.

PMID- 23539833
TI  - Diabetic retinopathy in children.
AB  - The risk of developing diabetic retinopathy (DR), the leading cause of vision
      loss among working-aged individuals, depends largely upon the duration of
      diabetes. Pediatric populations would appear to be at low risk for DR but it has
      been discovered in patients as young as 5.5 years and devastating cases of
      blindness have been reported in adolescents. Microvascular complications of
      diabetes, including DR, frequently develop during puberty, thereby making the
      detection of retinopathy important during these years and those of later
      adolescence. Retinopathy screening protocols have been written by several
      organizations but adherence by patients and physicians remains poor. Improved
      understanding of the risk factors for retinopathy, including many of the recently
      identified genetic abnormalities, may enable more effective and targeted
      screening of the diabetic population. Furthermore, advances in imaging technology
      promise to improve physicians' ability to effectively screen patients for
      retinopathy within their offices.

PMID- 23539834
TI  - Persistent Mullerian duct syndrome: 8 new cases in Southern California and a
      review of the literature.
AB  - Persistent Mullerian Duct Syndrome (PMDS) is a 46,XY disorder of sex development
      (DSD) in which Mullerian structures are found in genotypic males with normally
      virilized external genitalia and unilateral or bilateral cryptorchidism. It is
      usually diagnosed incidentally during surgical repair of cryptorchidism or
      inguinal hernia. The majority of cases are due to a mutation of the anti
      Mullerian hormone (AMH) gene or the AMH receptor, type II (AMH-RII) gene.
      Management of patients with PMDS requires a multidisciplinary approach. Long-term
      prognosis is good although fertility appears to be decreased and there may be a
      risk of malignancy due to cryptorchidism and retained Mullerian remnants. We
      describe 8 new cases of PMDS diagnosed in Southern California in the past 10
      years and review the literature.

PMID- 23539835
TI  - Maturity onset diabetes of the young: clinical characteristics, diagnosis and
      management.
AB  - Maturity Onset Diabetes of the Young (MODY), represents a rare cause of diabetes
      (1% of all cases), commonly misdiagnosed as Type 1 Diabetes (T1D) or Type 2
      Diabetes (T2D). Clinical characteristics of MODY include age of onset before 45
      years, absence of beta-cell autoimmunity and features of metabolic syndrome,
      sustained endogenous insulin production and strong family history. Common reasons
      for misdiagnosis are limitations in physicians' awareness and restrictions in
      performing genetic testing. In an attempt to improve diagnosis rates, recent
      research efforts have focused on the discovery of non-genetic biomarkers for
      prioritising individuals for genetic testing, with some promising progress
      (identification of high-sensitivity CRP, plasma glycan profile as HNF1A-MODY).
      The information provided is relevant to physicians dealing with young adults but
      details on pediatric populations are also included. Raising awareness about MODY
      and making the diagnosis more accessible will improve prognostication and
      management of these patients and their relatives.

PMID- 23539836
TI  - Meeting report: the 2012 FASEB Science Research Conference "The growth
      hormone/prolactin family in biology and disease" A novel biannual rendez-vous in
      the endocrinology landscape.
AB  - The inaugural edition of the FASEB Science Research Conference entitled 'The
      GHIPRL Family in Biology and Disease' was held this past summer at Snowmass,
      Colorado. This report provides an overview of the scientific content and a taste
      of the atmosphere of this novel meetinq in the field of Endocrinology.

PMID- 23539837
TI  - 2012 annual meeting of the Endocrine Society, Houston, Texas (June 23-26 2012)
      selected highlights.

PMID- 23539838
TI  - [The day after...].

PMID- 23539839
TI  - [Consensus on the end of life, report of the Sicard committee].

PMID- 23539840
TI  - [New indicators for the nursing care pathway].

PMID- 23539841
TI  - [Nursing education, mixed review by students].

PMID- 23539842
TI  - [Financing regulation of social security for 2013 and community care].

PMID- 23539843
TI  - [The place of the nurse in the vaccination programme in France].
AB  - Nurses are authorised to administer vaccines with a medical prescription or
      written protocol. Since 2008, they have been able to administer the seasonal
      influenza vaccine without a prescription to people at risk. A survey highlighted
      their need to improve their knowledge of vaccination. To meet this need, a task
      force made up of nurses and doctors has drawn up a handbook entitled Idevac.

PMID- 23539844
TI  - [Nursing training and changes of identity].
AB  - Over the last three decades, several European countries have implemented reforms
      to their nursing training systems. In French-speaking Switzerland, this training
      has been offered, since 2002, at university level in higher education
      institutions (Swiss university of applied sciences), while it is also taught to a
      higher level in graduate schools (Ecoles Superieures) in German- and Italian
      speaking Switzerland and, as of late, in just one French-speaking Swiss school.
      Some identity changes and tensions appear in the field for a number of reasons.
      The latter are also identified as being able to influence the professional
      development of nursing graduates of the Swiss university of applied sciences.

PMID- 23539845
TI  - [Developing nurses' motivational interviewing skills through coaching].
AB  - Developing skills in motivational interviewing enables nurses to prepare their
      patient for change by arousingtheir motivation. A two-day training course
      combined with three/four coaching sessions can be carried out in a clinical
      environment. This approach enables the nurse to acquire advanced skills.
      Motivational interviewing is an approach which is appreciated by nurses who need
      to draw on specific skills, requiring practice, regular coaching and feedback to
      develop and maintain these skills over the long-term.

PMID- 23539846
TI  - [Treatment of scars, an interdisciplinary collaboration].

PMID- 23539847
TI  - [Scars, physiology, classification and assessment].
AB  - A skin scar is the sign of tissue repair following damage to the skin. Once
      formed, it follows a process of maturation which, after several months, results
      in a mature scar. This can be pathological with functional and/or aesthetic
      consequences. It is important to assess the scar as it matures in order to adapt
      the treatment to its evolution.

PMID- 23539848
TI  - [The medical treatment of scars].
AB  - The medical treatment of scars follows the recommendations of experts working in
      this field. Traditional medical treatments include silicone, corticosteroid
      injections, radiotherapy, cryotherapy, 5-fluorouracil or bleomycin. Several other
      treatments are currently being assessed.

PMID- 23539850
TI  - [Physical therapy for scars].
AB  - Physical therapy consists notably of hand or mechanical massages, pressure
      therapy using various fabrics or splints, cryotherapy, laser therapy, etc. It
      forms part of the range of therapies used to treat pathological scars, including
      medical and surgical treatment. While the results are often satisfactory for
      hypertrophic scars, they remain uncertain for major keloids.

PMID- 23539849
TI  - [The surgical treatment of scars].
AB  - Scars can be functionally or socially disabling. Many patients affected therefore
      request corrective surgery. The list of surgical techniques is long and the most
      frequently-used solutions are well-known.

PMID- 23539851
TI  - [Scars and lasers].
AB  - Different lasers are used to improve scars in combination with other therapies.
      The pulsed dye laser is considered to be the gold standard for hypertrophic scars
      and keloids. Ablative laser treatments are used with atrophic scars. Ablative or
      non-ablative fractional laser treatments are developing rapidly due to the lower
      risk of infection and easier follow-up care.

PMID- 23539852
TI  - [Algorithms and combined treatments of scars].

PMID- 23539853
TI  - [Burn scars].
AB  - Burns often result in extensive scars which can change the body aesthetically
      and/ or functionally. Rapid scarring is a sign of a good prognosis. Preventative
      actions such as hydration, compression, massage, posture and splints help to
      prevent or contain the negative evolution of pathological scars.

PMID- 23539854
TI  - [Prevention of pathologic scars].

PMID- 23539856
TI  - [Bibliography].

PMID- 23539855
TI  - [What is the future for treating scars?].

PMID- 23539857
TI  - [Quantitative methodology and experimental studies 2/2].
AB  - Experimental studies potentially produce scientific evidence. To achieve this
      goal, it is necessary to pay particular attention to three elements essential for
      the validity of the study: randomisation, manipulation and control.

PMID- 23539858
TI  - [The course of patient nursing care, the overall process in the clinical
      pathway].

PMID- 23539859
TI  - [Supervised injection. Under the watchful eye of nurses].

PMID- 23539860
TI  - [Food sources of saturated fat may affect the risk of cardiovascular diseases].

PMID- 23539861
TI  - [The intrauterine device. Consider the contraindications].

PMID- 23539862
TI  - [Nurse power: from convincing results... to politics].

PMID- 23539863
TI  - [Pharmacologic treatment of arterial hypertension. 2].

PMID- 23539864
TI  - [The First Love teaching aid].

PMID- 23539865
TI  - [An experience in six steps].

PMID- 23539866
TI  - [Treatment of venous ulcers: compression therapy].

PMID- 23539867
TI  - [Spina bifida: a hope? A new corrective fetal surgery ].

PMID- 23539868
TI  - [Results of SATIN I (satisfaction of nurses): nursing care at the end of life].

PMID- 23539869
TI  - [VapoEclair. For smoking cessation].

PMID- 23539870
TI  - [Cymbalta. Also controls the pain of knee arthrosis].

PMID- 23539871
TI  - [Topical benzocaine. Warning].

PMID- 23539872
TI  - [Nasal decongestants and eye drops: keep out of children's reach!].

PMID- 23539873
TI  - [Pradax. A second study].

PMID- 23539874
TI  - [Travel: Indonesia].

PMID- 23539875
TI  - [Financing the purchase of the first home: REER, CELI or RAP?].

PMID- 23539876
TI  - Obligatory versus elective single embryo transfer in in vitro fertilization. A
      population-based analysis of data from the U.K. Human Fertilisation and
      Embryology Authority.
AB  - OBJECTIVE: To determine how obligatory single embryo transfer (SET) and elective
      SET influence pregnancy outcome. STUDY DESIGN: We compared women who underwent
      obligatory and elective SET using data from a comprehensive, population-based
      register from the United Kingdom Human Fertilisation and Embryology Authority,
      which contained all in vitro fertilization (IVF) treatments administered between
      1991 and 1998. Generalized estimating equations were used to generate adjusted
      odds ratios (ORs) and 95% confidence intervals (CIs) to compare clinical
      pregnancy, live birth, and multiple birth rates. RESULTS: Obligatory and elective
      SET had similar clinical pregnancy and live birth rates and comparable multiple
      birth rates. Obligatory and elective SET were equally likely to end in a live
      birth (OR = 1.08; 95% CI = 0.90, 1.30). Similar results were found after
      restricting the data to women without previous IVF births (OR = 1.18; 95% CI =
      0.98, 1.42) and without previous naturally conceived live births (OR = 1.16; 95%
      CI = 0.95, 1.43). CONCLUSION: This study suggests that obligatory SET can achieve
      pregnancy and live birth rates that are at least as good as elective SET. Equally
      important is the low multiple birth rate which was maintained in both forms of
      SET. More studies comparing elective versus obligatory SET can assist with
      achieving optimal pregnancy rates while preventing multiple births.

PMID- 23539877
TI  - Tuboovarian abscess. Factors associated with operative intervention after failed
      antibiotic therapy.
AB  - OBJECTIVE: To evaluate whether size of tuboovarian abscess (TOA) and other
      clinical characteristics were associated with the need for surgical intervention.
      STUDY DESIGN: A retrospective chart review of patients hospitalized at an inner
      city hospital between January 1998 and December 2007 with the diagnosis of TOA.
      Demographics, medical history, clinical markers of infection, radiology,
      pathology, and operative reports were examined. Student's t test and Fisher's
      exact test were utilized to analyze differences between groups. Multiple logistic
      regression analysis was performed to identify significant predictors of surgery.
      Receiver operating characteristic (ROC) analysis was used to assess how well TOA
      size and other significant variables were associated with the need for operative
      or procedural intervention. RESULTS: A total of 163 patients with TOA were
      identified; 41 patients were excluded based on specific criteria. Of the
      remaining 122 women, 65.6% responded to antibiotic therapy, and 34.4% had surgery
      or ultrasound-guided drainage. Mean TOA size in the medical group was 4.4 cm as
      compared to 7.3 cm in the surgical group (p < 0.0001). Maximal leukocyte count,
      older age, and parity were associated with significantly higher risk of surgery.
      The significant univariate variables remained significant after multivariate
      analysis. ROC curve analysis revealed an excellent discrimination of the need for
      surgical treatment as predicted by TOA size, with increased likelihood of
      surgical or procedural intervention with increasing TOA size. CONCLUSION:
      Radiographic size, leukocyte count, age, and parity are associated with operative
      or procedural treatment of tuboovarian abscess.

PMID- 23539878
TI  - Oxidative stress and inflammation in lean and obese subjects with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To determine whether polycystic ovary syndrome (PCOS) independently
      influences oxidative stress and inflammation or if the culprit is the
      comorbidities of obesity and/or insulin resistance common to this condition.
      STUDY DESIGN: Thirty women with PCOS were matched for age, body mass index and
      insulin resistance with 30 control subjects. Oxidative stress was examined by
      measuring the total oxidant status (TOS) and total antioxidant capacity (TAC) by
      spectrophotometric assay. The inflammatory biomarkers, C-reactive protein,
      plasminogen activator inhibitor-1, myeloperoxidase, neopterin, and serum amyloid
      A were measured by ELISA methodologies. RESULTS: Oxidative status was increased
      in the PCOS subjects relative to their weight-matched controls (TOS: obese PCOS
      patients vs. obese controls, 42.42 +/- 4.49 vs. 32.57 +/- 1.97, p<0.05; lean PCOS
      patients vs. lean controls, 33.69 +/- 1.59 vs. 28.69 +/- 1.18 micromol H2O2
      Equiv/L, p < 0.05). Furthermore, antioxidant capacity was lower in the lean PCOS
      group relative to their weight-matched controls (TAC: lean PCOS patients vs. lean
      controls, 1.10 +/- 0.09 vs. 1.49 +/- 0.03 nmol Trolox Equiv/L, p < 0.05).
      CONCLUSION: These results suggest that PCOS independently influenced oxidative
      stress. Overall, the presence of PCOS may increase cardiovascular risk.

PMID- 23539879
TI  - Obsessive-compulsive symptoms during the postpartum period. A prospective cohort.
AB  - OBJECTIVE: To estimate the prevalence of postpartum obsessive-compulsive disorder
      (OCD) symptoms and to ascertain risk factors for this condition. STUDY DESIGN:
      This is a prospective cohort of postpartum women carried out from June to
      September 2009. A total of 461 women were recruited after delivery at a tertiary
      care institution. Demographic, psychiatric, and obstetric information were
      collected from each participant. Patients were contacted at 2 weeks and at 6
      months postpartum and completed screening tests for depression, anxiety, and OCD.
      RESULTS: Eleven percent of women screened positive for OCD symptoms at 2 weeks
      postpartum. At 6 months postpartum almost half of those women had persistent
      symptoms, and an additional 5.4% had developed new OCD symptoms. Concomitant
      positive screens for anxiety and depression were predictive factors for the
      development of OCD symptoms. CONCLUSION: Prior population-based studies estimate
      the prevalence of OCD to be approximately 2-3%. We found much higher rates among
      women in the postpartum period. The postpartum period is a high-risk time for the
      development of OCD symptoms. When such symptoms develop, they have a high
      likelihood of persisting for at least 6 months.

PMID- 23539880
TI  - A critical appraisal of the potential harmful effects of terbutaline sulfate use
      in pregnancy.
AB  - Beta2-adrenergic agonist medications such as albuterol and terbutaline are often
      prescribed during pregnancy to treat conditions such as asthma, pulmonary
      disease, preterm labor, or acute non-reassuring fetal heart rate abnormalities
      during labor. Recently a review article questioned the safety of beta2-adrenergic
      agonist use in pregnancy, postulating a "biologically plausible" link between the
      use of these agents and autism spectrum disorder in offspring of mothers exposed
      to these drugs. While it is imperative to determine any harmful effects of any
      medication during pregnancy, it is important to weigh the risks and known
      benefits of treatment versus nontreatment of conditions such as preterm labor
      with medications such as terbutaline, given the known rates of morbidity and
      mortality associated with prematurity. The purpose of our review and commentary
      is to explain how and why beta2-adrenergic agonists are used to treat preterm
      labor and to discuss the merits of the conclusions drawn by the Witter clinical
      commentary.

PMID- 23539881
TI  - Insulin-like growth factor 2 and insulin-like growth factor 2 receptor gene
      polymorphisms in idiopathic male infertility.
AB  - OBJECTIVE: To test the association between insulinlike growth factor 2 (IGF2)
      ApaI and IGF2 receptor (IGF2R) Gly1619Arg gene polymorphisms and idiopathic male
      infertility. STUDY DESIGN: Polymerase chain reaction and restriction fragment
      length polymorphism methods were performed to detect the IGF2 ApaI and IGF2R
      Gly1619Arg genotypes in 98 Croatian men with idiopathic infertility and 113
      fertile men. RESULTS: There were no significant differences between patients and
      controls according to genotype (chi2(IGF2) = 3.46, p = 0.177; chi2(IGF2R) = 1.12,
      p= 0.571, respectively) and allele frequencies (chi2(IGF2) = 3.23, p = 0.072;
      chi2(IGF2R) = 0.99, p = 0.319, respectively). Odds ratios for recessive, dominant
      and codominant models and association testing with each genotype combination
      revealed no difference between infertile men and controls. CONCLUSION: In this
      study we have shown that IGF2 ApaI and IGF2R Gly1619Arg gene polymorphisms are
      not associated with male infertility.

PMID- 23539882
TI  - Is the protocol for induction of labor in singletons applicable to twin
      gestations?
AB  - OBJECTIVE: To evaluate the success of induction of labor in twin gestations using
      standard protocols for misoprostol and oxytocin designed for singleton
      gestations. STUDY DESIGN: This retrospective cohort study involved all diamniotic
      twin gestations that were induced at > or = 32 weeks' gestation with intact
      membranes. Two singleton pregnancies were matched for each twin pregnancy. Use of
      intravaginal misoprostol and low-dose intravenous oxytocin was based on ACOG
      management guidelines. RESULTS: A small proportion (40 of 430 [9.3%]) of twins
      met the inclusion criteria for an induction of labor. Misoprostol was utilized
      less frequently with twins than with singletons (55% vs. 78%, p = 0.02) because
      of the higher preinduction Bishop score. Doses of oxytocin were comparable
      between the 2 groups. A high rate of vaginal delivery was seen in the twin and
      singleton groups (85.0% vs. 80.0%, p = 0.62) with similar neonatal outcomes.
      CONCLUSION: A standard protocol of labor induction for singleton gestations would
      apply for twins with overall favorable intrapartum outcomes.

PMID- 23539883
TI  - Results of midtrimester emergency cerclage.
AB  - OBJECTIVE: To evaluate the outcomes of midtrimester emergency cerclage and to
      find out the contributing factors. STUDY DESIGN: Twenty-five patients presenting
      with cervical dilation and effacement with the membranes at the level of the
      external os or prolapsed into the vagina were included in the study. At the time
      of the cervical cerclage placement, gestational age ranged from 14-26 weeks. A
      good outcome was defined as the take-home baby rate, but also the interval
      between the time of the cervical cerclage placement and delivery and the
      gestational age at delivery were discussed. RESULTS: The mean gestational age at
      the time of the cervical cerclage placement was 21.2 +/- 2.73 weeks, the mean
      gestational age at delivery was 29.4 +/- 5.37 weeks, and the mean birth weight
      was 1,511 g. Eighteen patients had McDonald type cerclage, and 7 patients had
      both McDonald and Saling type cerclages. The overall take-home baby rate was 64%.
      Patients presenting with membranes at the level of external os had a take-home
      baby rate of 68.8%, whereas patients presenting with membranes prolapsed into the
      vagina had a take-home baby rate of 31.3%. CONCLUSION: Cervical dilation at
      midtrimester has a poor outcome which can be improved with emergency cerclage.
      Patients presenting with membranes prolapsed into the vagina have a decreased
      success rate. Total closure of the cervix may improve results.

PMID- 23539884
TI  - Clitoral subdermal hoodoplasty for medical indications and aesthetic motives. A
      new technique.
AB  - OBJECTIVE: To present a newly developed surgical intervention (clitoral subdermal
      hoodoplasty) for an asymmetrical clitoral prepucial thickness hypertrophy and to
      evaluate its applicability and outcomes. STUDY DESIGN: The study was conducted on
      3 consecutive patients with symptomatic, asymmetrical-in-thickness clitoral
      prepucial hypertrophy. A clitoral subdermal hoodoplasty surgical technique for
      asymmetrical clitoral prepucial thickness hypertrophy has never been described
      before. An observational prospective, multiple time series clinical study was
      conducted. Primary outcome measures were to determine applicability, outcomes,
      and potential complications of the new surgical intervention. Data collected
      included demographics, patient selections, intraoperative and postoperative
      complications, and outcomes of the newly developed surgical intervention.
      RESULTS: All subjects demonstrated subdermal hypertrophy of the clitoral prepuce.
      The newly developed procedures were successfully applied. Complications were not
      observed. The surgical intervention resulted in resolving medical symptoms and
      signs and provided pleasing aesthetic outcomes. In this study the procedure was
      simple to execute and well-tolerated by all subjects, without short-term and long
      term complications. CONCLUSION: Clitoral subdermal hoodoplasty is a useful method
      in the treatment of clitoral subdermal hypertrophy.

PMID- 23539885
TI  - Clinical comparison of ovarian stimulation and luteal support agents in patients
      undergoing GnRH antagonist IVF cycles.
AB  - OBJECTIVE: To explore the comparative efficacy, safety, and tolerability of
      agents used for ovarian stimulation and luteal support when applied in a
      population of women undergoing in vitro fertilization (IVF) using a gonadotropin
      releasing hormone (GnRH) antagonist protocol. STUDY DESIGN: A phase 4,
      multicenter, randomized, open-label, exploratory clinical trial was performed at
      7 assisted reproductive technology centers in the United States. Subjects
      included 173 women aged 18-42 years with a documented history of infertility who
      were undergoing IVF. Subjects were randomized to treatment with highly purified
      human menopausal gonadotropin (HP-hMG) or recombinant human follicle-stimulating
      hormone (rhFSH) for ovarian stimulation and progesterone vaginal inserts (PVIs)
      or intramuscular injection of progesterone in oil (PIO) for luteal support.
      Protocols for IVF followed the standard practices of participating centers within
      the parameters of the study. RESULTS: Biochemical, clinical, and ongoing
      pregnancy rates were the main outcome measures. Ongoing pregnancy rates for
      individual treatment groups ranged from 44.0-46.9%. No statistically significant
      differences were observed in pregnancy outcomes for the comparisons of HP-hMG vs.
      rhFSH or PVI vs. PIO. All study medications were generally safe and well
      tolerated. CONCLUSION: In this study HP-hMG and rhFSH were equally effective for
      ovarian stimulation during GnRH antagonist IVF cycles. Both PVI and PIO are
      viable options for luteal support.

PMID- 23539886
TI  - Antiadhesive role of human amniotic fluid on peritoneal adhesion formation in a
      rat model. Experimental study.
AB  - OBJECTIVE: To determine the role of human amniotic fluid (HAF) in preventing or
      reducing postoperative adhesions. STUDY DESIGN: Uterine horn adhesion model was
      carried out in 24 female Wistar rats. The animals were randomized into 4 groups:
      (1) control, (2) Ringer's lactate, (3) whole HAF, and (4) HAF depleted from cells
      and proteins. Adhesion grade and histologic findings of adhesion-carrying tissues
      were evaluated and groups were compared according to these parameters. RESULTS:
      Rats treated with whole HAF had less adhesion grade when compared to the control
      group, but the difference was not statistically significant. On the other hand,
      centrifuged amniotic fluid treatment significantly reduced peritoneal adhesion
      grade, fibrosis and inflammation (p < 0.05). CONCLUSION: Whole HAF seems to have
      no beneficial effect on peritoneal adhesion formation, but HAF depleted of
      protein and cells does have a positive effect on reducing adhesion formation.

PMID- 23539887
TI  - Incidence and determinants of peripartum hysterectomy in the metropolitan area of
      the District of Columbia.
AB  - OBJECTIVE: To review the impact of the changes that have occurred in the standard
      of care in obstetrics and in the trend of cesarean delivery rates in recent times
      and factors associated with peripartum hysterectomy procedure. STUDY DESIGN: A
      retrospective analysis of all cases of peripartum hysterectomies among inpatient
      hospitalizations at 4 major hospitals in the Washington metropolitan areas of the
      District of Columbia from January 1, 2000, through December 31, 2009, was
      conducted. RESULTS: The total number of deliveries and postpartum hysterectomies
      that occurred at all 4 locations was 150,847 and 128, respectively. The rate of
      peripartum hysterectomies per 1,000 deliveries was 0.85. Primary and repeat
      cesarean deliveries, advanced maternal age, obesity, and grand multiparity have
      direct association with peripartum hysterectomy. Up to 80% of all cases of
      peripartum hysterectomy are accounted for by class III and IV hemorrhage.
      Peripartum hysterectomy is associated with increased prevalence of uterine atony,
      placenta previa, and placenta accreta. CONCLUSION: Our results suggest that
      primary and repeat cesarean deliveries, advanced maternal age, obesity, and grand
      multiparity, uterine atony, placenta previa, and placental accreta, and class III
      and IV hemorrhage are independently associated with an increased risk for
      peripartum hysterectomy. These findings may be of concern given the increasing
      rate of cesarean deliveries in the District.

PMID- 23539888
TI  - Pregnancy after endometrial ablation. A report of three cases.
AB  - BACKGROUND: Pregnancies after endometrial ablation (EA) are rare and are
      associated with high morbidity, especially in the second and third trimesters.
      CASE: We report 3 cases of pregnancy after EA in which severe complications
      occurred during the first trimester. The first case concerns an unexpected
      pregnancy after EA in a 50-year-old woman. Hysterectomy via laparotomy was needed
      because of heavy bleeding and severe anemia. Pathology showed a complete
      hydatidiform mole without invasion. Ultrasound-guided in situ methotrexate
      injection could be a nonsurgical alternative to terminate an intrauterine
      pregnancy after EA when the pregnancy is located within uterine synechiae, as
      shown by the second case. The third case presented as an accreta placentation
      mimicking hyperplastic myometrial invasion in a 46-year-old patient. CONCLUSION:
      Because of the high morbidity of these pregnancies that could still occur after
      EA, patients need contraception after EA, and concomitant hysteroscopic
      sterilization should be proposed at the same time.

PMID- 23539889
TI  - Granular cell tumor of the uterine cervix. A case report.
AB  - BACKGROUND: Granular cell tumor (GCT) is a relatively rare and nearly always
      benign neoplasm that has been described in many sites and organs including the
      tongue, skin, subcutaneous tissue, breast, and vulva. However, it is rarely seen
      in the uterine cervix. CASE: We report a case of granular cell tumor of the
      cervix in a 38-year-old woman. Upon microscopic examination the tumor was found
      to comprise large polygonal cells with an abundant eosinophilic granular
      cytoplasm and round to oval nuclei. Upon immunohistochemical staining the large
      cells showed S-100, neuron specific enolase, and CD68 positive in the cytoplasm.
      Clinical presentation of the patient, histopathological features of the lesion,
      and treatment approach are discussed. CONCLUSION: GCTs of the cervix are
      extremely rare. To the best of our knowledge this report is the first Chinese
      case of cervical GCT in the English-language literature. GCTs should always be
      considered during the diagnosis process with large cell lesions of the cervix.
      Extensive surgical resection appears to be adequate for most GCTs. Because of the
      unpredictable clinical outcome of this tumor, strict and long-term follow-up are
      recommended.

PMID- 23539890
TI  - Possible association between maternal lithium therapy and premature closure of
      the arterial duct. A case report.
AB  - BACKGROUND: Frequent causes of premature ductal closure include spontaneous
      idiopathic closure in utero and maternal use of nonsteroidal anti-inflammatory
      drugs late in pregnancy. CASE: We describe a case of a preterm infant born to a
      mother treated with lithium throughout pregnancy who presented with right-sided
      cardiac enlargement at 18 weeks' gestation. Immediately following delivery,
      echocardiography demonstrated a small closing patent arterial duct. CONCLUSION:
      We recommend that serial fetal echocardiography with emphasis on Doppler
      interrogation of the patent arterial duct be performed whenever a pregnant woman
      is taking lithium. The interrogation of the patent arterial duct is particularly
      important if right-sided chamber enlargement is noted at fetal sonography as this
      finding can be an early manifestation of premature ductal constriction.

PMID- 23539891
TI  - Health coverage for America: signed, sealed, and delivered by the 2012 election.

PMID- 23539892
TI  - Bouncers, brokers, and glue: the self-described roles of social workers in urban
      hospitals.
AB  - Social workers delivering services in health care settings face unique challenges
      and opportunities. The purpose of this study was to solicit input from social
      workers employed in urban hospitals about their perceptions of the roles,
      contribution, and professional functioning of social work in a rapidly changing
      health care environment. Using qualitative methods, the university and hospital
      based research team conducted seven focus groups (n = 65) at urban hospitals and
      analyzed the data using an interpretive framework with ATLAS.ti software. Seven
      major themes emerged from the participants' description of their roles: bouncer,
      janitor, glue, broker, firefighter, juggler, and challenger. Along with
      descriptions of the ways social workers fulfilled those roles, participants
      articulated differences in status within those roles, the increasing complexity
      of discharge planning, and expectations to provide secondary support to other
      health care professionals on their teams. Implications for practice and research
      are discussed.

PMID- 23539893
TI  - Department of health and human services changes: implications for hospital social
      workers.
AB  - In April 2010, President Obama issued a directive to the Secretary of Health and
      Human Services (HHS) regarding patient visitation, advance directives, and other
      initiatives to improve the lives of lesbian, gay, bisexual, and transgender
      people and their families. The HHS response to this directive has implications
      for hospital social workers. The purpose of this secondary data analysis was to
      explore indicators of social work readiness to support implementation of the
      resulting initiatives. A historical context for the changes is provided,
      inclusive of the cases that spurred the presidential memorandum. The findings are
      presented within the framework of the profession's standards for social work
      practice in health care and end-of-life care. Recommendations for enhancing
      social work readiness for a critical role in implementation of the new
      regulations are presented.

PMID- 23539895
TI  - Effect of service barriers on health status of aging South Asian immigrants in
      Calgary, Canada.
AB  - This study examined the relationships between service barriers and health status
      of aging South Asian immigrants. Data were obtained through a structured
      telephone survey with a random sample of 220 South Asians 55 years of age and
      older. The effect of the different types of service barriers on the physical and
      mental health of participants was examined using hierarchical multiple
      regression, while adjusting for participants' sociocultural demographic
      backgrounds. An average of 5.9 types of service barriers were reported. Among the
      four major types of barriers--cultural incompatibility, personal attitude,
      administrative problems, and circumstantial challenges--more barriers related to
      personal attitude predicted less favorable physical and mental health. In regard
      to health prevention, culturally appropriate strategies should be developed and
      implemented to help aging South Asians to overcome barriers related to personal
      attitude so that they can have better access to appropriate services.

PMID- 23539894
TI  - Unequal burden of disease, unequal participation in clinical trials: solutions
      from African American and Latino community members.
AB  - African Americans and Latinos are underrepresented in clinical trials. The
      purpose of this study was to elicit solutions to participation barriers from
      African Americans and Latinos. Fifty-seven adults (32 African Americans, 25
      Latinos) ages 50 years and older participated. The Institute of Medicine's
      Unequal Treatment conceptual framework was used. Six racially/ ethnically
      homogenous focus groups were conducted at five sites in three counties. Themes
      within groups and cross-cutting themes were identified. The NVIVO program was
      used for data classification. The data were reviewed for final coding and
      consensus. Shared solutions included addressing costs, recruiting in community
      contexts, conducting community and individualized patient education, and sharing
      patient safety information. Participants were unanimously in favor of clinical
      trials navigation recruitment interventions. Solutions specific to African
      Americans included diversifying research teams, recognizing past research abuses,
      and increasing community trust. Solutions specific to Latinos included providing
      low-literacy materials, providing Spanish-speaking clinicians and advocates, and
      clarifying that immigration status would neither be documented nor prevent
      participation. Solutions from African Americans and Latinos reflect their
      cultural backgrounds and historical experiences. The results suggest the
      importance of developing a tailored, barriers-focused navigation intervention to
      improve participation among diverse racial and ethnic populations.

PMID- 23539896
TI  - Incorporating discussion of sibling violence in the curriculum of parent
      intervention programs for child abuse and neglect.

PMID- 23539897
TI  - RNA interference-mediated knockdown of DGAT1 decreases triglyceride content of
      bovine mammary epithelial cell line.
AB  - Diacylglyceroltransferase-1 (DGAT1) expresses in nearly all tissues, including
      the mammary gland. Mice lacking DGAT1 exhibit decreased triglyceride content in
      mammary tissue, and are resistant to diet-induced obesity and diabetes mellitus.
      Thus, DGAT1 has received considerable attention. In the present study, the
      function of DGAT1 was examined by liposome mediated RNA interference (RNAi) to
      knockdown the expression of endogenous DGAT1 expression in bovine mammary
      epithelial cells (BMEC) and the changes of the biological functions of cells were
      analyzed. The mRNA and protein levels, intracellular triglyceride (TG) content,
      and total protein of BMECs were analyzed by real-time PCR, Western blot, TG kit,
      and ultraviolet spectrophotometer, respectively, before and after RNAi treatment.
      The results indicated that knockdown of DGAT1 expression significantly reduced TG
      content in BMECs. This study further confirmed the importance of DGAT1 in
      triglyceride synthesis in bovine mammary tissue.

PMID- 23539898
TI  - Involvement of ITIH5, a candidate gene for congenital uterovaginal aplasia (Mayer
      Rokitansky-Kuster-Hauser syndrome), in female genital tract development.
AB  - The ITI (inter-trypsine inhibitor) gene family includes five genes (ITIH1 to
      ITIH5) that encode proteins involved in the dynamics of the extracellular matrix
      (ECM). ITIH5 was found inactivated by partial deletion in a case of congenital
      uterovaginal aplasia, a human rare disease also called Mayer-Rokitansky-Kuster
      Hauser (MRKH) syndrome. The aim of the present study was to analyze the
      expression of ITIH5 in the uterus in adult life and during embryogenesis in order
      to establish the involvement of this gene in both normal and pathological
      conditions of uterus development. This was achieved in mice by reverse
      transcription-quantitative PCR, whole-mount hybridization, and Western blot
      analysis. Itih5 expression was much stronger in female genital tract primordia
      (Mullerian ducts) and derivatives than elsewhere in the body. This gene was
      strongly expressed during pregnancy and development of the female genital tract,
      indicating that the encoded protein probably had an important function in the
      uterus during these periods. Two different specific isoforms of the protein were
      detected in Mullerian derivatives during embryogenesis and in adults. Although
      ITIH genes are expected to be predominantly expressed in the liver, ITIH5 is
      mainly expressed in the uterus during development and adult life. This tends to
      indicate an additional and specific role of this gene in the female reproductive
      tract, and furthermore reinforces ITIH5 as a putative candidate gene for MRKH
      syndrome.

PMID- 23539899
TI  - Identification of genotypes of plasmid-encoded AmpC beta-lactamases from clinical
      isolates and characterization of mutations in their promoter and attenuator
      regions.
AB  - We investigated the occurrence of AmpC beta-lactamases among Escherichia coli and
      Klebsiella pneumoniae isolates and determined the genotype of plasmid-mediated
      AmpC beta-lactamases at a medical center. The AmpC beta-lactamase promoter and
      attenuator were amplified from chromosomal DNA of high AmpC-producing E. coli
      isolates and sequenced. Antibiotic screening and 3D extract tests showed the
      presence of AmpC beta-lactamase in 3.56% of K. pneumoniae and 1.88% of E. coli
      isolates. Ten isolates (six K. pneumoniae and four E. coli) were positive for
      extended spectrum beta-lactamase (ESBL) as indicated by the double disc diffusion
      method. DHA-1 plasmid-encoded AmpC beta-lactamase was present in 10 K. pneumoniae
      isolates and four E.coli isolates. E. coli chromosomal AmpC beta-lactamase
      carried polymorphisms in the -42, -32, and -18 bases of the promoter and in the
      +26 and +27 bases of the attenuator, which may play a role in antibiotic
      resistance. The observed mutations may have clinical implications for the
      management of antibiotic-resistant infections.

PMID- 23539900
TI  - Statins cause profound effects on gene expression in human cancer cells in vitro:
      the role of membrane microdomains.
AB  - There is increasing evidence that statin treatment can be beneficial in certain
      cancer patients. To determine if these benefits are a direct result of the
      cholesterol-lowering effects of statins or a result of secondary, protein
      transcription effects, the impacts of pravastatin and a cholesterol sequestrating
      agent methyl-beta-cyclodextrin (MbetaCD) on mRNA expression in the breast cancer
      cell MDA-MB-231 and the lung carcinoma cell Calu-1 have been compared by
      microarray techniques. The effects of these agents on cholesterol-rich rafts and
      caveolae, which have significance in cancer signaling, have also been examined.
      Both treatments caused a general downregulation of not only signal transduction
      including cancer pathway proteins, but also apoptosis and chemokine pathways,
      with statins impacting 35 genes by twofold or greater in MDA-MB-231 and > 300
      genes in Calu-1. These manifold dysregulations could also explain the various
      side effects reportedly caused by statins. MbetaCD produced far fewer statistical
      events than pravastatin in the breast cancer line but many more in the lung cell
      line. Pravastatin increased expression of CAV1 but caveolae density decreased and
      overall raft density was unaffected. MbetaCD also caused an increase in CAV1
      expression and reduced the prevalence of both rafts and caveolae. It is proposed
      that sequestration of cholesterol from the membrane by MbetaCD is not equivalent
      to blockade of the cholesterol pathway and causes different effects on
      microdomain-mediated signal transduction dependant on the cell line. The profound
      effects of statins on mRNA expression can be explained by the failure of caveolin
      1 to properly complex with cholesterol in an altered sterol environment, with
      caveolae acting as the main loci for signaling directed towards those
      transcription processes unaffected by MbetaCD. Targeted inhibition of the
      postmevalonate pathway could offer an opportunity to specifically reduce caveolae
      based signaling in cancer cells. The observed impact of pravastatin on gene
      expression may explain the pleiotropic effects of statins when they are used as
      adjuvants in chemotherapy and suggests impact on gene expression as a possible
      cause of side effects from statin use.

PMID- 23539901
TI  - Cystathionine gamma-lyase expression is regulated by exogenous hydrogen peroxide
      in the mammalian cells.
AB  - Hydrogen sulfide (H2S), as an endogenous signaling molecule in mammals, shows a
      variety of biological effects. Cystathionine gamma-lyase (CSE)/H2S pathway has
      been implicated in scavenging reactive oxygen species (ROS) in the mammalian
      cells. Therefore, we first investigated the regulatory effects of exogenously
      applied hydrogen peroxide (H2O2) on CSE expression in the mammalian cells.
      African green monkey kidney fibroblastlike cells (COS-7 cells) or human embryonic
      kidney 293 cells (HEK 293 cells) were transfected with CSE promoter-luciferase
      reporter constructs and treated with H2O2 of 1, 5, and 10 microM for 0.5 and 1.5
      h at 37 degrees C. The transfected cells were assayed for firefly luciferase
      activities normalized by Renilla luciferase activity. Human lung adenocarcinoma
      cells (A549 cells) or human liver cancer cells (SMMC-7721 cells) were treated
      with H2O2 of 1, 5, and 10 microM for 0.5 and 1.5 h at 37 degrees C, and were then
      harvested and analyzed by Western blotting and quantitative RT-PCR. Our results
      showed that the treatment of a medium concentration (5 microM) of H2O2 at a
      longer time (1.5 h) upregulated CSE expression in the mammalian cells at the
      levels of the promoter, message RNA, and protein. Collectively, exogenously
      applied H2O2 can not only markedly affect CSE mRNA and protein expression, but
      also can affect the CSE promoter activity in the mammalian cells. Our
      observations indicate that that exogenous H2O2 can upregulate the expression of
      the CSE gene in the mammalian cells, which will provide the possibility of the
      scavenging effect of the CSE gene indirectly on ROS in the mammalian cells.
      However, the regulatory mechanism involved in the effects of exogenously applied
      H2O2 on CSE expression in the mammalian cells need be further studied.

PMID- 23539902
TI  - Computational approaches for identifying cancer miRNA expressions.
AB  - MicroRNAs (miRNAs) play a major role in cancer development and also act as a key
      factor in many other diseases. In this investigation, we propose three methods
      for handling miRNA expressions. The first two methods determine whether a miRNA
      is indicating normal or cancer condition, and the third one determines how many
      miRNAs are supporting the cancer sample/patient. While Method 1 acts as a two
      class classifier and is based on normalized average expression value, Method 2
      also does the same and is based on the normalized average intraclass distance.
      Method 3 checks whether a miRNA belongs to the cancer class or not, provides the
      percentage of supporting miRNAs for a cancer patient, and is based on weighted
      normalized average intraclass distance. The values of the weights are determined
      using exhaustive search by maximizing the accuracy in training samples. The
      proposed methods are tested on the differentially regulated miRNAs in three types
      of cancers (breast, colon, and melanoma cancer). The performances of Method 1 and
      Method 2 are evaluated by F score, Matthews Correlation Coefficient (MCC), and
      plotting "1--specificity versus sensitivity" in Receiver Operating Characteristic
      (ROC) space and are found to be superior to the kNN and SVM classifiers for
      breast, colon, and melanoma cancer data sets. It is also observed that both the
      sensitivity and the specificity of Method 1 and Method 2 are higher than 0.5. For
      the same data sets, Method 3 achieved an average accuracy of more than 98% in
      detecting the miRNAs, supporting the cancer condition.

PMID- 23539903
TI  - Application of the Ommaya reservoir in the treatment of hydrocephalus in
      prematurely born children: correlation with animal results.
AB  - INTRODUCTION: Intraventricular hemorrhage occurs in almost one fifth of
      prematurely born children. Due to present complications, such as hydrocephalus
      and neurological deficit, it endangers the child's life, therefore there is the
      need for understanding and prevent risk factors as well as the need for finding
      most optimal methods of treatment. OBJECTIVE: The aim of the study was to point
      out the current therapeutic modalities of the treatment of posthemorrhagic
      hydrocephalus in prematurely born children. METHODS: The study included 60
      patients divided into two groups of 30 patients treated at the University
      Children's Hospital of Belgrade in the period 2003-2008. RESULTS: Treatment
      outcome of the control group of patients treated by standard methods was
      influenced by gestational age (p=0.024), head circumference on birth (p = 0.043),
      body mass on birth (p = 0.006), Apgar score on birth (p < 0.001), peripartum
      asphyxia (p < 0.001), cardiorespiratory arrest (p < 0.001), respiratory distress
      (p = 0.002) and intraventricular hemorrhagic grade (p < 0.001). As statistically
      significant predictors of the poor treatment outcome of the experimental group of
      patients treated by using Ommaya reservoir were identified: low body mass on
      birth (p < 0.05), low Apgar score (p < 0.05), prolonged number of days on
      assisted ventilation (p < 0.05), presence of peripartum asphyxia (p < 0.05) and
      cardiorespiratory arrest (p < 0.05). CONCLUSION: No statistically significant
      difference was detected in the outcome between the patients treated by the
      standard method and those with installed Ommaya reservoir. However, the
      difference of 10% in mortality between the two groups may be clinically
      significant so that further studies of larger samples are necessary.

PMID- 23539904
TI  - [Clinical profile of presumed and definitive ocular sarcoidosis].
AB  - INTRODUCTION: Sarcoidosis is an antigen-mediated disease of unknown cause defined
      by granulomatous inflammation of different organs. OBJECTIVE: The aim of this
      study was to analyze the clinical picture in 26 patients with a definitive and
      presumed ocular sarcoidosis. METHODS: The following tests were conducted:
      angiotensin-converting enzyme, tuberculin skin test, liver enzymes and calcium in
      urine and serum. Enlarged hilar lymph glands were diagnosed using X-ray
      tomography or computed tomography of the mediastinum. A biopsy of lymph glands
      was performed either transbronchially or transmediastinally. Ophthalmic
      examination included biomicroscopic examination, intraocular pressure
      measurement, photofundus, fluorescein angiography, optical coherence tomography
      and computerized perimetry. RESULTS: The average follow-up period of the disease
      was 6.1 years. The average age was 52.0 years. There were 62.5% female patients,
      with bilateral incidence of 69.2%. The clinical picture included: panuveitis (in
      30.8% of patients), anterior uveitis (26.9%), posterior uveitis (26.9%),
      intermediate uveitis (7.7%) and vitritis in (7.7%). The following complications
      were observed: cataract (in 34.6% of patients), cystoid macular edema (23.1%),
      glaucoma (15.4%), macroaneurysms (15.4%), neovascularization (7.7%) and band
      keratopathy (3.8%). There was a statistically significant difference in the
      visual acuity (p = 0.033) and severity of clinical symptoms (p = 0.02) between
      the groups of patients with retinal vasculitis associated with"candle-wax"
      phenomenon and the group of patients with multiple chorioretinal lesions--"white
      dot" syndrome. CONCLUSION: To our consideration, the differences observed between
      the two groups are the result of retinal vasculitis and subsequent macular edema,
      which is significantly more frequent in the group with"candle-wax" phenomenon.

PMID- 23539905
TI  - Prostaglandin E2 in apical tissue fluid and postoperative pain in intact and
      teeth with large restorations in two endodontic treatment visits.
AB  - INTRODUCTION: Acute periapical inflammation is the most common cause of
      postoperative pain developing as a result of mechanical, chemical and/or
      microbial injury of periapical tissue. The major inflammatory event responsible
      for periapical pain is increased vasodilatation and vascular permeability, partly
      caused by prostaglandin E2, with consequent edema, which leads to the compression
      of nerve fibers. OBJECTIVE: The aim of this study was to determine the
      concentrations of prostaglandin E2 in apical tissue fluid after endodontic
      treatment of intact and teeth with large restorations and to compare it with the
      occurrence and intensity of postoperative pain. METHODS: Single-rooted teeth of
      24 patients, selected for this study, were distributed into two groups: intact
      (group 1, n = 27) and asymptomatic teeth with large restorations (group 2, n =
      20). Clinical examination of the involved teeth included the electric pulp test,
      recording pain on percussion, spontaneous pain, and a radiographic examination.
      Samples of apical tissues fluid were obtained from root canals at two treatment
      visits, and prostaglandin E2 concentrations were measured using radioimmunoassay.
      Pain intensity was assessed by visual analogue scale. RESULTS: Prostaglandin E2
      concentrations at the second visit, in teeth with large restorations, was
      significantly higher (36%) than at the first treatment visit (Wilcoxon signed
      rank test, p < 0.05). Occurrence and intensity of spontaneous pain after the
      first visit were significantly higher in group 2 (p < 0.05) than in group 1.
      CONCLUSION: These results suggest that the increased prostaglandin E2
      concentration, caused by endodontic treatment of teeth with large restorations,
      is well correlated with the intensity of postoperative pain.

PMID- 23539906
TI  - [Postmarketing study of efficacy and safety of losartan during the treatment of
      patients with mild and moderate hypertension: LOTAR (corrected) study].
AB  - INTRODUCTION: Losartan, the angiotensin type 1 receptor blocker (ARB) exercises
      its main antihypertensive effect by vasodilatation of peripheral arteries.
      OBJECTIVE: The aim of this study was to evaluate the antihypertensive effect and
      safety of losartan in patients with mild and moderate arterial hypertension (AH).
      METHODS: This was an open post-marketing study with losartan as monotherapy in
      previously treated or untreated patients with AH. Primary efficacy parameter was
      the percentage of patients that achieved target blood pressure after 8-week
      treatment with a single daily dose of losartan of 50-100 mg. Safety parameters
      were assessed according to the percentage of adverse events and metabolic effects
      of therapy. RESULTS: The study included 550 patients with AH (59% female and 41%
      male), mean age 56.8 +/-11.4 years, BMI = 27 +/- 4 kg/m2. Losartan was applied in
      31% of untreated and 69% of previously treatment-resistant patients After 8 weeks
      target blood pressure was achieved in 67.8% (SBP) and in 81.1% (DBP) of patients,
      respectively. The mean decrease was 21.8% for SBP and 21.1% for DBP (p < 0.001).
      Out of all, 65% of patients achieved both target SBP and DBP values.
      Hydrochlorothiazide was added to the therapy in 11.6% of patients. There were no
      significant differences in drug efficacy between the entire group and subgroups
      of patients with diabetes mellitus and impaired renal function (p = ns). Adverse
      events were rare and metabolic effect was favorable. CONCLUSION: Monotherapy with
      losartan in a dosage of 50-100 mg applied during 8 weeks resulted in achieving
      target values of blood pressure in 65% of patient with mild and moderate
      hypertension, also including the patients with diabetes mellitus and impaired
      renal function. Losartan is a safe and metabolically neutral medication.

PMID- 23539907
TI  - Effects of combination of AT1-antagonist candesartan cilexetil and ACE-inhibitors
      in patients with congestive heart failure.
AB  - INTRODUCTION: Combination of ACE-inhibitors with angiotensin-II type 1 receptor
      antagonists could provide better blockade of RAAS system compared with
      monotherapy. OBJECTIVE: The aim of this study was to evaluate hemodynamic and
      neurohumoral effects at rest and during exercise of Candesartan cilexetil as add
      on therapy to ACE-inhibitors in patients with heart failure NYHA class III to IV.
      METHODS: This was a prospective, randomized, double-blind, placebo-controlled,
      parallel group study. Thirty-five patients received either Candesartan 8 mg/16 mg
      (1st and 2nd week/ of 3-24) or placebo as add-on therapy to their previous ACE
      inhibitor during a 24-weeks treatment period. RESULTS: Peak aerobic capacity
      remained constant in the Candesartan group of patients (0.06 +/- 1.43 mL/min/ kg)
      and slightly decreased in the placebo group (-1.10 +/- 1.51 mL/min/kg), without a
      statistically significant difference between the groups (p = 0.13). Exercise time
      showed a relevant increase in the Candesartan (31.9 +/- 58.5 sec) and a
      significant decrease in the placebo group (-25.9 +/- 85.9 sec) compared to
      baseline value. The difference between the studied groups was statistically
      significant (p < 0.001). Relevant differences between the two groups were
      observed in the changes of right atrial pressure at rest (Candesartan: -1.9 +/-
      1.7 mmHg, placebo: 1.0 +/- 2.7 mmHg, p < 0.01), pulmonary capillary wedge
      pressure at rest (Candesartan: -3.1 +/- 3.8 mmHg, placebo: 0.2 +/- 4.6 mmHg, p <
      0.05) and systemic vascular resistance at maximum exercise (Candesartan: -141.9
      +/- 253.3 dyne*sec/cm5, placebo: 47.3 +/-221.0 dyne*sec/cm5, p < 0.05).
      CONCLUSION: The efficacy of CHF treatment of congestive heart failure was
      moderately improved by Candesartan as add-on therapy to ACE-inhibitors.

PMID- 23539908
TI  - [Etiology of growth hormone deficiency in children and adolescents].
AB  - INTRODUCTION: Growth hormone deficiency (GHD) can be isolated or associated with
      deficiency of other pituitary gland hormones. According to age at diagnosis,
      causes of GHD are divided into congenital or acquired, and according to etiology
      into recognized and unknown. OBJECTIVE: We analyzed etiology and prevalence of
      GHD, demographic data at birth, age, body height (BH) and bone age at diagnosis
      as well as the frequency of other pituitary hormone deficiencies. METHODS: The
      study involved 164 patients (109 male).The main criterion for the diagnosis of
      GHD was inadequate response of GH after two stimulation tests.The patients were
      classified into three groups: idiopathic, congenital and acquired GHD. RESULTS:
      Idiopathic GHD was confirmed in 57.9% of patients, congenital in 11.6% and
      acquired in 30.5%. The mean age at diagnosis of GHD was 10.1 +/- 4.5 years.The
      patients with congenital GHD had most severe growth retardation (-3.4 +/- 1.4
      SDS), while the patients with idiopathic GHD showed most prominent bone delay (
      3.6 +/- 2.3 SDS).The prevalence of multiple pituitary hormone deficiency was
      56.1%, in the group with congenital GHD 73.7%, acquired GHD 54.0% and idiopathic
      GHD 53.7%.The frequency of thyrotropin deficiency ranged from 88.2-100%, of
      adrenocorticotrophin 57.1-68.8% and of gonadotrophins deficiency 57.1-63.0%,
      while deficiency of antidiuretic hormone was 2.0-25.0%. CONCLUSION: Although
      regular BH measurements enable early recognition of growth retardation, patients'
      mean age and degree of growth retardation indicate that GHD is still diagnosed
      relatively late. A high incidence of other pituitary hormone deficiencies
      requires a detailed investigation of the etiology of disorders and evaluation of
      all pituitary functions in each child with confirmed GHD.

PMID- 23539909
TI  - Relationships between obesity, lipids and fasting glucose in the menopause.
AB  - INTRODUCTION: Menopause leads to the development of central adiposity, a more
      atherogenic lipid profile and increased incidence of metabolic syndrome
      independent of age and other factors. OBJECTIVE: The aim of the study was to
      investigate the relationships between anthropometric characteristics, sex
      hormones, lipids and fasting glucose in menopausal women. METHODS: The study
      included 87 menopausal women, who where divided into groups according to two
      criteria: BMI > or = 26.7 kg/m2 and BMI > or = 25 kg/m2. Anthropometric
      characteristics and blood pressure were measured. Blood was taken at 08.00 h for
      fasting glucose, triglycerides, cholesterol, HDL, LDL, apolipoprotein A,
      apolipoprotein B, lipoprotein(a) (Lp(a)), C-reactive protein, fibrinogen,
      follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL),
      estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG).
      RESULTS: Significant differences between groups were found for weight, BMI,
      waist, hips circumference, waist/hip ratio (WHR), systolic and diastolic blood
      pressure, Lp(a), FSH, LH, PRL (for systolic blood pressure p < 0.05, for the rest
      p < 0.01) and fasting glucose (p < 0.05). In obese and overweight women with BMI
      > or = 26.7 kg/m2 significant negative correlations were found for FSH and
      glucose, SHBG and LDL, SHBG and total cholesterol, SHBG and glucose, BMI and HDL,
      WC and HDL. In obese and overweight women with BMI > or = 25 kg/m2 significant
      negative correlations were found for BMI and HDL, waist circumference (WC) and
      HDL, WHR and HDL, FSH and glucose, SHBG and glucose; significant positive
      correlations were between BMI and glucose, WC and glucose and WHR with
      triglycerides. CONCLUSION: Gaining weight and decreased SHBG are related to
      dyslipidemia and increased fasting glucose confirming increased incidence of
      metabolic abnormalities in the menopause.

PMID- 23539910
TI  - [Invasive isolates of Streptococcus pneumoniae in Serbia: antimicrobial
      susceptibility and serotypes].
AB  - INTRODUCTION: Streptococcus pneumoniae is one of the leading causes of bacterial
      meningitis and sepsis. Invasive pneumococcal disease is a significant medical
      problem worldwide, particularly in children, due to a huge increase of
      pneumococcal resistance to antibiotics. OBJECTIVE: The aim of the study was to
      investigate the antimicrobial susceptibility pattern of invasive pneumococcal
      isolates, as well as to determine whether decreased S. pneumoniae susceptibility
      to antibiotics was related to a particular serotype. METHODS: Antimicrobial
      susceptibility to 19 antibiotics was determined in 58 invasive pneumococcal
      strains that were collected from seven regional centers during the period July
      2009 to February 2011 in the National Reference Laboratory for streptococci and
      pneumococci. RESULTS: The overall nonsusceptibility rate to penicillin was
      detected in 34% of pneumococcal isolates and to erythromycin in 36%. Higher
      resistance rates were observed among children than among adults. Penicillin
      resistance rate was 65% in children versus 22% in adults, while erythromycin
      nonsusceptibility rate was 47% in children versus 32% in adults. Co-resistance to
      penicillin and erythromycin was detected in 21% strains, mostly isolated from
      children. Multiresistance was found in one third of isolates. All strains were
      susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and
      rifampicin, while 23 (40%) isolates were susceptible to all tested antibiotics.
      The most common resistant serotypes were 19F and 14. CONCLUSION: The study has
      revealed that penicillin and macrolide resistance among invasive pneumococcal
      isolates is very high in Serbia. This emphasizes the need for continuous
      monitoring for invasive pneumococcal disease to document the serotype
      distribution and antimicrobial susceptibility pattern.

PMID- 23539911
TI  - [Observational study in primary health care: symptoms control of gastroesophageal
      reflux disease and influence on the quality of life].
AB  - INTRODUCTION: Gastroesophageal reflux disease (GERD) is a common disease in
      primary care. The most effective medicamentous treatment is proton pump
      inhibitors (PPI). OBJECTIVE: Observational study conducted in 13 primary health
      care centers from the whole Serbia with the aim to collect local epidemiology
      data on GERD and to investigate the intensity and frequency of disease symptoms
      and the quality of life of patients treated with proton pump inhibitors by using
      a Patient's Questionnaire. METHODS: Adult GERD patients treated with PPI were
      under follow-up for two months. The investigators evaluated typical symptoms and
      gave global assessment of disease severity. The patients filled-in the Patient's
      Questionnaire on disease symptoms and quality of life. At the study end, the
      investigators evaluated the importance of the Patient's Questionnaire in the
      management of these patients. RESULTS: The study included 828 patients (66.3%
      female) of mean age 54.8 years. The most common life habits were coffee
      consumption (86.1%), exposure to stress (81.7%), smoking (45.7%) and alcohol
      consumption (25%). With PPI therapy a statistically significant reduction of
      typical GERD symptoms of any intensity was detected as evaluated by the
      investigators (p < 0,001), as well as the reduction in the frequency of all
      symptoms and accompanying discomforts of the quality of life, as estimated by the
      patients (p < 0.001). In 92.2% of the patients the investigators evaluated the
      Patient's Questionnaire to be of significant help. CONCLUSION: Primary health
      care physicians evaluated the Patient's Questionnaire as an important tool in the
      investigation of the disease symptoms and the quality of life of patients with
      GERD. The intensity and frequency of symptoms were reduced, and the quality of
      life of patients with GERD was improved by therapy with PPI.

PMID- 23539913
TI  - Attitudes on alcohol and drinking patterns among youth in Serbia.
AB  - INTRODUCTION: Alcohol is most abused psychoactive substance among youth.
      Analyzing attitudes on alcohol, patterns and consequences we are getting inputs
      important for implementing evidence based preventive measures. OBJECTIVE: The aim
      of this study was to analyze drinking patterns and expectations and alcohol risk
      perception by gender and region and determine correlation between attitudes and
      one year prevalence of drinking. METHODS: The study used data from the European
      School Survey on Alcohol and Other Drugs, which was then conducted in 2008 in
      Serbia on a sample of 6,553 students aged 16 years. For data analysis descriptive
      and analytical statistic were used. RESULTS: The results show that nine out often
      students have had at least one alcoholic beverage during life and 5% have at
      least one alcohol beverage on more than 20 occasions during the last month.
      Students in Serbia have mainly positive expectations from alcohol, and the
      strongest potential drinking predictors in the previous year are expectation of
      having fun and the wish to feel relaxed. According to the participants, drinking
      4-5 drinks on weekends (34.6%) is less risky than trying cannabis (52.0%). Boys
      have experienced problems caused by alcohol drinking more often than girls, while
      students from Vojvodina have performed badly in school in higher percentage than
      students from Belgrade and Central Serbia. CONCLUSION: In Serbia, girls drink
      less and perceive drinking as more risky in comparison to boys, while 16-year-old
      students from Vojvodina have more positive expectations but also more prominent
      problems caused by alcohol drinking. Additional education of the young on alcohol
      risk is recommended.

PMID- 23539912
TI  - [Ondansetron, alfentanil and nitrous oxide in the prevention of pain on injection
      of propofol].
AB  - INTRODUCTION: Propofol is a widely used intravenous anesthetic with a number of
      advantages over intravenous anesthetics used so far.The leading side effect is
      pain on injection. OBJECTIVE: Aim of the study was to determine the impact of
      ondansetron, nitrous oxide and alfentanil on reducing pain during propofol
      application. METHODS: The paper presents a prospective, randomized, single blind
      study. The study included 120 patients of ASA class I and II, who underwent
      elective surgery under general anesthesia using propofol for the induction of
      anesthesia. The patients were divided into four equal groups of 30 patients.The
      control group received a few milliliters of saline, N group the mixture of nitric
      oxide and oxygen, O group ondansetron and group A received alfentanil. In all
      patients, venous occlusion was performed for 60 seconds. Pain assessment was
      based on the criteria and the score by McCrirrick and Hunter. RESULTS: Pain after
      the application of propofol was present in 47 (39.2%) patients. The highest
      frequency of pain was recorded in the control group (18, 60%), and significantly
      lower (p = 0.009) in the patients who received ondansetron (8; 26.7%) and (p =
      0.020), alfentanil (9; 30%).The statistical analysis proved that there was a
      significant relationship between the groups and the scale of pain (Chi2 = 13.849,
      p = 0.031). CONCLUSION: Based on the results of our study we can conclude that
      intravenous ondansetron and alfentanil with venous occlusion can effectively
      prevent pain during IV use of propofol.

PMID- 23539914
TI  - [Balneological classification of mineral waters of Serbia].
AB  - INTRODUCTION: Balneological classification of the main occurrences and deposits
      of mineral, thermal and thermomineral waters of Serbia is based on the
      classification by V. V. Ivanov from 1977. This classification after countless and
      numerous check-ups on the international level has been accepted by the Commission
      for Mineral Waters of the International Association of Hydrogeology (IAH).
      OBJECTIVE: The main goal of this paper is to show the complexity and mutual
      connections of all activities while distinguishing the main links and
      regularities of legalities on the relation hydrogeological environment and human
      health. METHODS: As the basis of this study we used all up-to-date long-term
      detailed geological, hydrogeological, hydrochemical, balneological and numerous
      other researches of multidisciplinary character with their specific methods and
      research results, followed by their analysis and synthesis. RESULTS: From the
      review of up-to-date classifications, it is evident that by their comparison
      common elements can be found, but not also adequate application when forming
      classification schemes, which results in the statement that there are only a few
      all-encompassing classifications that reflect the conditions of formation,
      existence, renewal and flowing out of mineral waters, which is the basis for the
      application in balneology. One such classification is that by V.V.Ivanov that is
      usable and conforms to our experiences and needs. Results of all previous
      detailed geological, hydrogeological and numerous other studies with
      multidisciplinary character represent the basis for these investigations.
      CONCLUSION: The suggested classification is recommended for future application in
      balneological sciences, because by the application of this classification all
      those involved in the research and usage of mineral waters would represent and
      treat them in a clear, distinct and unified manner based on scholarly confirmed
      foundations.

PMID- 23539915
TI  - [Intraocular foreign body removal: case report].
AB  - INTRODUCTION: An intraocular foreign body may traumatize the eye mechanically,
      introduce infection or exert other toxic effects on the intraocular structures.
      Removal of a metallic intraocular foreign bodies (IOFB) use an internal
      (vitrectomy followed by forceps or internal magnet use) or external approach
      (large electromagnet). OUTLINE OF CASES: A 51-year-old man sustained injury of
      the left eye by a metal foreign body. On admission visual acuity was normal (VOS
      = 1.0) and intraocular tension was within normal limits (TOS = 10 mmHg). Nasal
      scleral entry wound was noticed. Ultrasound of the left eye was done, which
      confirmed existence of IOFB laying nasally, next to the ciliary body. Extraction
      of IOFB with a big electric magnet was done. Visual acuity on discharge was the
      same (VOS = 1.0). Another man, aged 30 years, came to the clinic after injury of
      the left eye by a foreign body. On admission visual acuity was VOS = L + P+
      (light and projection), TOS = 44 mmHg (higher), traumatic cataract, scleral entry
      wound, corneal edema, existence of IOFB and initial endophtalmitis. Lensectomia
      and vitrectomia via pars plana with IOFB extraction were done.Visual acuity on
      discharge was VOS = 5/60 with +6.50 Dsph = 0.3-0.4; TOS= 7 mmHg. CONCLUSION:
      Magnet removal is indicated in patients when IOFB is laying free in the vitreous
      body or stopped near the entry wound during injury without other complications.
      Internal approach--pars plana vitrectomy with forceps removal is used when IOFB
      is stuck either on the peripheral or posterior part of the retina or if there are
      some of aforementioned complications.

PMID- 23539916
TI  - [Infective endocarditis--maybe yes, maybe no: case report].
AB  - INTRODUCTION: Infective endocarditis (IE) is a rare disease which manifests in
      different ways. CASE OUTLINE: We are presenting a female patient who was
      suspected of IE based on the presence of fever, accelerated erythrocyte
      sedimentation rate, increased levels of C-reactive protein and echocardiographic
      findings of filamentous structures on the aortic valve which were assumed to be
      vegetation. Because of the well-known fact that in the pre-antibiotic era IE was
      almost always a fatal disease, empirical antibiotic therapy was conducted despite
      the absence of clear criteria for IE and it resulted in a satisfactory outcome.
      The course of the disease and the persistence of echocardiographic findings with
      a completely competent aortic valve, suggested us to consider the diagnosis of
      Lambl's excrescences. There was no indication for surgical treatment in our
      patient; so that in the absence of pathological confirmation our diagnostic
      dilemma was left unresolved. CONCLUSION: In patients with typical clinical
      features of IE and filamentous structures on the cardiac valves that are
      completely competent, Lambl's excrescences should be kept in mind as a possible
      differential diagnosis.

PMID- 23539917
TI  - [Hybrid procedure in the treatment of thoracoabdominal aortic aneurysms: case
      report].
AB  - INTRODUCTION: Treatment of thoracoabdominal aortic aneurysms is a major problem
      in vascular surgery. Conventional open repair is associated with significant
      rates of mortality and morbidity and therefore, there is a need for better
      solutions. One of them is a hybrid procedure that includes visceral debranching.
      This paper presents the first such case performed in Serbia, with a brief
      overview on all published procedures worldwide. CASE OUTLINE: A 57-year-old woman
      was admitted to the hospital because of thoracoabdominal aneurysms type V by
      Crawford-Safi classifications. Because of the significant comorbidities it was
      concluded that conventional treatment would bear unacceptably high perioperative
      risk, and that the possible alternative could be the hybrid procedure in two
      stages. In the first stage aortobiliacal reconstruction with bifurcated Dacron
      graft (16 x 8 mm) and visceral debranching with hand made tailored branched graft
      was done. In the second act, the thoracoabdominal aneurysm was excluded with
      implantation of the endovascular Valiant stent graft, 34 x 150 mm (Medtronic,
      Santa Rosa, CA). Control MSCT angiography showed a proper visceral branch patency
      and positioning of the stent graft without endoleaks. Nine months after the
      procedure the patient was symptom-free, with no aneurysm, diameter change and no
      graft-related complication. All visceral branches were patent. CONCLUSION: So far
      about 500 cases of visceral debranching have been published with the aim of
      treating thoracoabdominal aneurysms, and still we have no valid guidelines
      concerning this method. However, in carefully selected high-risk patients this is
      an excellent alternative to open surgery of thoracoabdominal aneurysms.

PMID- 23539918
TI  - Spontaneous rupture of giant liver hemangioma: case report.
AB  - INTRODUCTION: Hemangioma is the most frequent benign solid tumor of the liver. It
      is well known that a giant liver hemangioma carries the risk of spontaneous
      rupture, followed by hemoperitoneum and hemorrhagic shock with possible fatal
      outcome. CASE OUTLINE: This is a case report of the spontaneous rupture of a
      giant cavernous hemangioma of the liver in an 85-year old patient.The patient was
      presented with abdominal pain and hemorrhagic shock. Emergency ultrasonography
      and computed tomography of the abdomen showed a heterogeneous ruptured solid
      tumor of the right liver lobe, multiple cysts in the left lobe and massive
      hemoperitoneum. The patient was successfully managed by immediate exploratory
      laparotomy, surgical enucleation of the hemangioma under intermittent inflow
      vascular occlusion, temporary perihepatic packing and planned second look
      relaparotomy. CONCLUSION: Immediate surgical procedure is indicated mandatory in
      unstable patients with a ruptured giant hemangioma of the liver. Surgical
      enucleation under intermittent inflow vascular occlusion and temporary
      perihepatic packing could be a life-saving procedure in those patients.

PMID- 23539919
TI  - Forearm reconstruction after loss of radius: case report.
AB  - INTRODUCTION: Osteomyelitis of the radius resulting in the radial clubhand is a
      very rare condition and few studies have been published about its prognosis and
      treatment. CASE OUTLINE: This is a case report of hematogenous osteomyelitis of
      the radius with a complete loss of the radius leaving only the distal radial
      metaphysis to carry the carpus. In order to achieve best functional results, four
      step operative protocol was performed for reconstruction; lengthening of the
      forearm by external fixator, radioulnar transposition to create a one-bone
      forearm, plate removal and transposition of brachioradialis to the extensor
      pollicis longus as well as proximal row carpectomy. After nine years of the last
      operation, the function of the elbow and hands is good with acceptable cosmetic
      result. The forearm is 5 cm shorter and there has been a persistent mild
      limitation of palmar flexion. CONCLUSION: Creation of the one-bone forearm
      normalizes the elbow and wrist function, corrects forearm malalignment, and
      improves forearm growth potential.

PMID- 23539920
TI  - [Modern statin therapy in clinical practice: the lower the better].
AB  - Lipid and lipoprotein disorders are well known risk factors for atherosclerosis
      and its complications. The level of atherogenic LDL-cholesterol (LDL-C) is
      directly related to an increased risk of occurrence and progression of ischemic
      heart disease. Epidemiological and clinical studies have shown that the use of
      statin therapy to decrease LDL-C can significantly reduce the incidence of
      mortality, major coronary events and the need for revascularization procedures in
      the different groups of patients. The findings of a large meta-analysis conducted
      by the Cholesterol Treatment Trialists' (CTT) collaborators showed that every 1.0
      mmol/l reduction of atherogenic LDL-C is associated with a 22% reduction in
      cardiovascular diseases mortality and morbidity. However, despite the impressive
      results of the benefits of statin therapy, the EUROASPIRE study showed that about
      50% of patients with ischemic heart disease did not achieve target LDL-C levels.
      According to the new ESC/EAS Guidelines for the Management of Dyslipidaemias in
      patients with a very high cardiovascular risk, treatment goal should be to
      decrease LDL-C below 1.8 mmol/l or > or = 50% of initial values. In the majority
      of patients that can be achieved by statin therapy. For this reason an adequate
      choice of statins is of crucial importance, whereby the needed reduction in
      atherogenic LDL-C, after the identification of its target level based on the
      assessment of total cardiovascular risk, can be achieved.

PMID- 23539921
TI  - [Novelties in gout].
AB  - Chronic asymptomatic hyperuratemia (HUA), gout paroxysm in patients with chronic
      hyperuratemia (HU) and normouricemic attacks of gouty arthritis are well known,
      but poorly understood. A review of the current literature with attempt of its
      explanation is presented. The natural course of gout is associated with joint
      structure changes that may be evaluated by different imaging techniques;
      comparative advantages and shortcomings of each technique are presented. For
      almost over 50 years the market has not offered new drugs for the control of HU
      and gout, while management of such patients was a rather neglected field. Over
      the last five years an unpredictable number of prospective clinical studies have
      been conducted involving the investigation of the efficacy and safety of new
      drugs to control HU (febuxostat, pegloticase). The return of pharmaceutical
      industry into the world of gout has considerably changed the picture. New
      recommendations have been presented on appropriate colchicine dose regime for
      acute gouty flares. Emerging therapies, including pegloticase, uricosuric agent
      RDEA596 and the interleukin-1 inhibitors have shown promises in early and late
      phase clinical trials. Each of them deserves to be considered for implementation
      and feasibility in clinical practice as well as outcome measures for clinical
      trials. Another purpose of this review was to summarize new knowledge on approved
      drugs to treat hyperuricemia, or the clinical manifestations of gout. Results of
      several clinical trials provide new data on the efficacy and safety of the
      approved urate lowering drugs (allopurinol and febuxostat). Lifestyle and dietary
      recommendations for gout patients should take into consideration overall health
      benefits and risks, since gout is often associated with metabolic syndrome and an
      increased future risk of cardiovascular disease and mortality. This review also
      summarizes the recent data about lifestyle factors that influence serum uric acid
      levels and the gout risk, and attempts to provide holistic recommendations,
      considering both their impact on gout as well as on other health implications.

PMID- 23539922
TI  - [Sexual dimorphism and specificities of psychopharmacological treatment in
      women].
AB  - The scope of gender related differences observed in mentally ill persons provides
      a major source of inference about the role of gonadal steroids in brain function
      and behavior. Reported gender dimorphism in psychiatry includes the following:
      prevalence of certain mental disorders specific to female gender, phenomenology
      and treatment characteristics, i.e. response to the applied
      psychopharmacotherapy. Structural and functional relationship between the
      hormonal system and central nervous system is closely correlated with
      vulnerability to various psychopathological disturbances in biologically
      different stages in women. It has been observed, for instance, that the
      association of gonadal steroid activity with serotonin is relevant to mood change
      in premenstrual and postpartum mood disturbances. Gender related hormonal
      fluctuations may cause or be correlated with the development of several gender
      related psychopathological disturbances. The aim of this article is to review the
      literature concerning gender-related specificities of psychopharmacological
      treatment of some of the most important mental disorders in women, such as
      affective disorder in menopause, premenstrual syndrome and postpartum mood
      disorders.

PMID- 23539923
TI  - Celiac disease.
AB  - Celiac disease is a multysystemic autoimmune disease induced by gluten in wheat,
      barley and rye. It is characterized by polygenic predisposition, high prevalence
      (1%), widely heterogeneous expression and frequent association with other
      autoimmune diseases, selective deficit of IgA and Down, Turner and Williams
      syndrome. The basis of the disease and the key finding in its diagnostics is
      symptomatic or asymptomatic inflammation of the small intestinal mucosa which
      resolves by gluten-free diet. Therefore, the basis of the treatment involves
      elimination diet, so that the disorder, if timely recognized and adequately
      treated, also characterizes excellent prognosis.

PMID- 23539924
TI  - [Ethics and reproductive health: the issue of HPV vaccination].
AB  - The ethics of reproductive health covers a wide field of different issues, from
      the ethical dimensions of assisted reproduction, life of newborns with
      disabilities to the never-ending debate on the ethical aspects of abortion.
      Furthermore, increasing attention is paid to the ethical dimensions of using stem
      cells taken from human embryos, the creation of cloned embryos of patients for
      possible self-healing, and the increasingly present issue of reproductive
      cloning. Development of vaccines against human papillomavirus (HPV) has
      introduced new ethical aspects related to reproductive health and the need for a
      consensus of clinical and public-healthcare population. Today immunization with
      HPV vaccine is a measure for the primary prevention of cervical cancer and it
      provides effective protection against certain types of viruses included in the
      vaccine. The most often mentioned issues of discussions on ethical concerns about
      HPV vaccination are the recommended age of girls who should be informed and
      vaccinated (12-14 years), attitudes and fears of parents concerning discussion
      with their preadolescent daughters on issues important for their future sexual
      behavior, dilemma on the vaccination of boys and the role of the chosen
      pediatrician in providing information on the vaccination. In Serbia, two HPV
      vaccines have been registered but the vaccination is not compulsory. Up-till-now
      there has been no researches on the attitudes of physicians and parents about HPV
      vaccination. Nevertheless, it is very important to initiate education of general
      and medical public about the fact that the availability of vaccine, even if we
      disregard all aforementioned dilemmas, does not lead to the neglect of other
      preventive strategies against cervical cancer, primarily screening. The National
      Program for Cervical Cancer Prevention involves organized screening, i.e. regular
      cytological examinations of the cervical smear of all women aged 25-69 years,
      every three years, regardless of the vaccination status.

PMID- 23539925
TI  - [Olga Palic-Szanto (1890-1971), M.D., Ophthalmologist: biographical notes].
AB  - Dr. Olga Palic-Szanto lived in Serbia working as an ophthalmologist from 1919 to
      1947. We were able to follow her life and work from documents found in the
      archives of Belgrade and Novi Sad. Olga Szanto was born in 1890 in Gyoma,
      Hungary. Having completed the studies of medicine in Budapest and Berlin she
      worked with the First Eye Clinic of the University of Budapest with the famous
      Professor Emil Gross for six years. In 1919 she moved to Novi Sad and in 1921 to
      Belgrade and worked at the Eye Department of the General State Hospital for one
      and a half years. Until the beginning of the Second World War she worked at
      several outpatient ophthalmology departments of several hospitals. Olga Palic
      Szanto published a great number of papers in prominent medical journals of Europe
      and America. We were able to identify as many as 58 titles of her published works
      which cover different fields of ophthalmology. In the journal "Serbian Archives
      of Medicine"we traced four of her studies published in between the two world
      wars, two of which we discuss in this paper. She was an active public figure in
      Belgrade and elsewhere, not only in the field of ophthalmology but also as a
      member of the Association of University-Educated Women and Women's League for
      Peace and Freedom. She returned to Hungary probably in 1947, where she continued
      to write and publish a number of papers. Dr. Olga Palic-Szanto died in Budapest
      in 1971.

PMID- 23539926
TI  - The occurrence of small for gestational age infants and perinatal and maternal
      outcomes in normal and poor maternal weight gain singleton pregnancies.
AB  - OBJECTIVE: To assess the occurrence of small for gestational age (SGA) infants
      and perinatal and maternal outcomes in singleton pregnancies with normal and poor
      maternal weight gain. MATERIAL AND METHOD: Pregnant women with normal pre
      pregnancy body mass index (BMI) and attending the antenatal clinic at King
      Chulalongkorn Memorial Hospital (KCMH) between 2006 and 2010 were eligible for
      the present study. The Thai population guidelines recommend a total weight gain
      of 10 to 16 kg or > or = 0.27 kg/week during pregnancy. In contrast, in 2009 the
      Institute of Medicine (IOM) guidelines recommended a total weight gain of 11.5 to
      16 kg or > or = 0.31 kg/week. Our patients were analyzed using both sets of
      guidelines based on a normal pre-pregnancy BMI (18.5-24.9 kg/m2). SGA infants,
      perinatal outcomes, and maternal outcomes were compared between women whose
      weight gain met or exceeded the recommendations (normal weight gain) and women
      who did not meet these recommendations (poor weight gain). RESULTS: A case
      control of 1,152 singleton pregnancies was used for the analyses. Women with poor
      weight gain by the recommendation of the Thai population guidelines were
      significantly associated with SGA infants (1% in normal weight gain group and
      2.6% in poor weight gain group adjusted odd ratio (aOR) 2.77, 95% confidence
      interval (CI) 1.06 to 7.28), preterm births (aOR 2.20, 95% CI 1.43 to 3.38), and
      low birth weight (LBW) infants (aOR 2.57, 95% CI 1.60 to 4.13). Women with poor
      weight gain by the recommendation in the 2009 IOM guidelines were significantly
      associated with preterm births (aOR 2.04, 95% CI 1.31 to 3.17), LBW infants (aOR
      2.75, 95% CI 1.66 to 4.55), but not SGA infants (aOR 1.97, 95% CI 0.74 to 5.20).
      Maternal weight gain < 0.27 kg/week (Thai guidelines) was more likely to
      associate with SGA infants than maternal weight gain < 0.31 kg/week (2009 IOM
      guidelines). Women with normal weight gain by both recommendations were more
      likely to have pregnancy-induced hypertension and less likely to have gestational
      diabetes compared with women with poor weight gain. CONCLUSION: Poor maternal
      weight gain during pregnancy was associated with SGA infants, preterm births, and
      LBW infants. The Thai guidelines were a better predictor of SGA infants. The 2009
      IOM guidelines should be used with caution in Thai patients.

PMID- 23539927
TI  - Universal screening of gestational diabetes mellitus: prevalence and diagnostic
      value of clinical risk factors.
AB  - OBJECTIVE: To estimate the prevalence of Gestational Diabetes Mellitus (GDM) by
      using universal screening and to show the diagnostic value of the clinical risk
      factors at Lampang Hospital. MATERIAL AND METHOD: This is a cross sectional
      study. Data were collected prospectively at the antenatal care clinic of Lampang
      Regional Hospital between January 4 and September 30, 2010. All pregnant women of
      appropriate gestational age (GA) were screened by glucose challenge test (GCT)
      then by oral glucose tolerance test (OGTT) if the GCT result was abnormal. Data
      were calculated for the prevalence of GDM and the diagnostic value of clinical
      risk factors. RESULTS: Six hundred thirteen pregnant women enrolled into the
      present study with 593 women left for the analysis. The prevalence of GDM at
      antenatal care clinic of Lampang Hospital was 9.3%. Among GDM cases, 21.8% had no
      risk factor Having one risk factor double the chance of having GDM, while having
      three risk factors gives 42.9% chance of having GDM. Having at least one risk
      factor could allow better detection with sensitivity of 78.2, specificity of
      49.8, PPV of 13.7, NPV of 95.7, LR+ of 1.6 and LR- of 0.4. This would produce
      52.8% of pregnant women at risk. CONCLUSION: With GDM prevalence of 9.3%, our
      population should be classified to the high prevalence group. Among GDM cases,
      21.8% had no risk factor. Moreover with 95.7% NPV and 0.4 LR-, this would make
      this set of risk factors merely a fair screening test. This should prompt the re
      evaluation of risk-based screening policy that is generally adopted throughout
      the country. Cost-effectiveness is the only major concern for the deployment of
      the universal screening program. It has to be further studied in an evidence
      based manner.

PMID- 23539928
TI  - Clinical characteristic and clinical course of aborted sudden cardiac death
      patients with structurally normal heart in King Chulalongkorn Memorial Hospital.
AB  - BACKGROUND: PED (Primary electrical disease) is an arrhythmogenic disease group
      that causes serious ventricular tachyarrhythmia in the absence of recognized
      structural heart disease. Although Thailand, which is a part of Southeast Asia,
      is an endemic area of PED, especially Brugada syndrome, there is little known
      about demographic data and clinical outcome of PED among survivors of sudden
      cardiac death (SCD). OBJECTIVE: To study demographic data and clinical outcome of
      PED among survivors of SCD in Thailand. MATERIAL AND METHOD: The present study
      was approved by the ethics committee of the Faculty of Medicine, Chulalongkorn
      University, Bangkok. The authors reviewed patient medical records for clinical
      characteristics, etiology, and clinical outcome of survivors of SCD between
      January 2002 and December 2008. The patients with PED who had normal structural
      heart and no obvious non-cardiac causes of sudden death were enrolled. RESULTS:
      Fifty-two survivors of SCD with PED (mean age 39 +/- 12, 49 males), mainly from
      the northeast and middle regions of Thailand, were recruited for this study. SCD
      mainly occurred during times when patients were asleep or resting (50% and 15.4%)
      respectively. Of the 52 survivors, 21 patients (40%) had a documented family
      history of SCD. The etiology of survivors of SCD is composed of Brugada syndrome
      (63.5%), Early repolarization syndrome (ERS) (9.6%). Congenital long QT syndrome
      (LQTS) (7.7%), and idiopathic VF (3.8%). Remaining 15.4% had abnormal ECG but not
      compatible with any etiology. A large number of patients (78.8%) completely
      recovered without neurological sequelae. The recurrence of severe ventricular
      arrhythmia occurred in 27 patients (51.9%) during mean follow-up period 56.5 +/-
      35.4 months (4 to 137 months). The recurrence was highest during the first year
      (32%) of follow-up. CONCLUSION: The Brugada syndrome is the most common etiology
      of survivors of SCD with normal structural heart in Thailand Although the
      prognosis after resuscitation was good, recurrence was especially high during the
      first year and as a result, an ICD implantation is needed for prevented
      recurrence of SCD.

PMID- 23539929
TI  - Smoking and death in Thai diabetic patients: the Thailand Diabetic Registry
      cohort.
AB  - OBJECTIVE: To determine the impact of smoking and quit smoking on mortality rate.
      MATERIAL AND METHOD: This prospective cohort was a three-year follow-up of Thai
      Diabetes Registry project that registered 9,370 diabetic patients from 10
      diabetic clinics in tertiary medical centers in Bangkok and major provinces
      between April 2003 and February 2006. RESULTS: The groups of 7,487 (80%), 1,315
      (14%), and 568 (6%) patients were classified as non-smokers, ex-smokers, and
      current smokers. The crude death rate of ex-smokers (Hazard Ratio (HR) 1.52 (95%
      CI 1.19-1.95)) and current smokers (HR 1.55 (1.10-2.19)) were higher than death
      rate of non-smokers. After control for covariates, the HR comparing ex-smokers
      with non-smokers was not different (1.10 (0.81-1.50)), while the HR comparing
      current smokers with non-smokers remained statistical significant (1.74 (1.17
      2.61)). CONCLUSION: Smoking increases mortality rate in diabetic patients by
      about 74%. Quitting smoking decreased mortality rate to the same rate as of
      diabetic non-smokers.

PMID- 23539930
TI  - Diagnosis and management of congenital adrenal hyperplasia: 20-year experience in
      Songklanagarind Hospital.
AB  - OBJECTIVE: To describe the types of congenital adrenal hyperplasia (CAH) in Thai
      children, and the clinical and laboratory findings associated with each type.
      MATERIAL AND METHOD: The medical records of CAH patients, aged 0 to 15 years,
      were retrospectively reviewed. RESULTS: During the 20-year period (1991-2011),
      there were 66 CAH patients. The most common type was salt-wasting 21-hydroxylase
      deficiency (21-OHDSW) (59.1%), followed by simple virilizing 21-hydroxylase
      deficiency (21-OHDSV) (30.3%), 20, 22-desmolase/steroidogenic acute regulatory
      protein (20,22D/StAR) deficiency (6.1%), and 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD) deficiency (4.5%). The stimulated cortisol level was < 18 microg/dL
      in most patients, with 20 cases of 21-OHDSV having a median level of 19.49
      microg/dL. The median basal 17-hydroxyprogesterone (17-OHP) levels were markedly
      elevated in 21-OHDSW and 21-OHDSV patients (20,264 and 5,985 ng/dL,
      respectively), but was very low in 20, 22D/StAR deficiency patients (260 ng/dL).
      Bilateral adrenal enlargement, demonstrated by radioimaging, was helpful for
      diagnosis of 20,22D/StAR and 3beta-HSD deficiency CONCLUSION: The most common
      type of CAH in our population was 21-hydroxylase deficiency. The steroid profile
      of cortisol, 17-OHP and testosterone levels is helpful for clinical diagnosis of
      21-OH deficiency. The low 17-hydroxyprogesterone and low cortisol levels in
      phenotypic female infant with salt-wasting crisis suggests the diagnosis of 20,
      22D/StAR deficiency CAH.

PMID- 23539931
TI  - Clinicopathological study of primary superficial leiomyosarcomas.
AB  - BACKGROUND: Primary superficial leiomyosarcomas (PSL) are rare malignant lesions
      that are subdivided into cutaneous and subcutaneous tumors. Primary cutaneous and
      subcutaneous leiomyosarcomas differ not only as to primary site of origins, but
      also to differences in prognosis. Guidelines for management and follow-up are not
      clearly defined in the literature. MATERIAL AND METHOD: Retrospective review was
      conducted from the patient's chart between January 2000 and December 2009.
      Histopathology, immunohistochemistry, and clinical and surgical records were
      reviewed. RESULTS: The authors found five cases of PSL and divided them into two
      cases of cutaneous leiomyosarcomas and three cases ofsubcutaneous
      leiomyosarcomas. Overall, mean age of the patients was 42.4 years, male: female
      ratio was 4:1. Clinical presentations were painless mass. Wide excisions were
      performed in three cases with 2 cm margins. No local recurrence was found in the
      period of follow-up (6 months to 3 years). One case presented with bony
      metastasis five years after operation. CONCLUSION: PSL are rare tumors. Surgical
      resection remains the main option for curative treatment. Wide excision with at
      least 2 cm peripheral margins and a depth that includes subcutaneous tissue and
      fascia are recommended. The natural history of these tumors is not clearly
      defined. All patients should be followed-up for a period of at least five years
      after treatments. The authors hoped that further study of these tumors would
      result in better treatments and follow-up guidelines to be a benefit to such
      patients in the future.

PMID- 23539932
TI  - Estrogen and progesterone receptors in patients with bladder pain syndrome.
AB  - OBJECTIVE: Analyze if bladder mucosa of patients with bladder pain syndrome (BPS)
      have more estrogen receptor (ER) and progesterone receptor (PR) than the normal
      population. MATERIAL AND METHOD: Between July 2009 and December 2010, 15 female
      patients with chronic bladder pain syndrome and 10 female patients without
      bladder pain were enrolled in the present study. Three pieces of trigonal bladder
      mucosa were biopsied and sent for estrogen receptor and progesterone receptor
      immunohistochemistry staining by the Benchmark automated machine. The results
      were reported as positive and negative and then compared between the two groups.
      RESULTS: Estrogen receptor was found in 14 out of 15 patients in the BPS group
      (93%) and in 7 out of 10 patients in the control group (70%). Progesterone
      receptor was found in 10 out of 15 patients in the BPS group (66.7%) and 5 out of
      10 patients in the control group. Both were not significantly different with p =
      0.267 and p = 0.678, respectively. CONCLUSION: The authors concluded that ER and
      PR might not play a role in the etiopathogenesis of BPS/IC. However other
      receptors should be further investigated about their role in this type of pain.

PMID- 23539933
TI  - A comparison of dexmedetomidine and propofol in Patients undergoing
      electrophysiology study.
AB  - BACKGROUND: Dexmedetomidine provides profound levels of sedation without
      affecting cardiovascular and respiratory stability based on its pharmacological
      profile. It may be a valuable sedative for procedures with minimal to mild pain.
      Electrophysiology study (EP study) is a mildly painful procedure that requires
      conscious sedation. The authors hypothesized that dexmedetomidine would cause
      lower respiratory and cardiovascular depression than propofol during equal
      sedation level in an electrophysiology study. MATERIAL AND METHOD: The present
      study protocol was approved by the clinical research ethics committee at
      Ramathibodi Hospital. Thirty-four patients were randomly allocated into two
      groups to receive either dexmedetomidine or propofol for an electrophysiology
      study. Patients in the dexmedetomidine group received a loading dose of
      dexmedetomidine (0.5 mcg/kg) infused over 10 minutes followed by 0.4 mcg/kg/h.
      Each patient in the propofol group received propofol 1 mg/kg over 10 minutes
      followed by 3 mg/kg/h. All patients received pethidine (0.5 mg/kg) before the
      initiation of EP study. Sedation was determined using the Modified Observer's
      Assessment of Alertness/Sedation (MOAA/S). The Modified Observer's Assessment of
      Alertness/Sedation scores, hemodynamic and respiratory variables were recorded
      regularly during the EP study. RESULTS: Thirty-four patients were enrolled in the
      present study. The Modified Observer's Assessment Alertness/Sedation values were
      similar in both groups. Respiratory rate values with dexmedetomidine were
      significantly higher than those in the propofol group (p = 0.048) and the oxygen
      supplement in the dexmedetomidine group were significantly lower than those in
      the propofol group (p < 0.001). Moreover mean arterial blood pressure values of
      dexmedetomidine at the five and 15-minute were significantly higher than those of
      the propofol group (p = 0.024). No incidence of severe bradycardia or hypotension
      was found in both groups. CONCLUSION: The present study demonstrated that
      comparable sedation could be achieved by a combination of pethidine with either
      dexmedetomidine or propofol during EP study. Dexmedetomidine group provided more
      hemodynamic and respiratory stability than propofol group.

PMID- 23539934
TI  - Plasma concentrations of bupivacaine after spinal anesthesia with single shot
      femoral nerve block in total knee arthroplasty.
AB  - BACKGROUND: Femoral nerve block is commonly established for postoperative
      analgesia in total knee arthroplasty but no evidence of plasma bupivacaine level
      has been reported. OBJECTIVE: Determine the plasma concentrations of bupivacaine
      in patients who had single-injection of femoral nerve block. MATERIAL AND METHOD:
      A prospective observational study was undertaken with 25 patients scheduled for
      unilateral total knee arthroplasty under spinal anesthesia and single shot
      femoral nerve block with 20 mL of 0.5% bupivacaine. Venous blood samples were
      collected at 0, 5, 10, 15, 30, 60, 90, and 120 minutes after femoral nerve block.
      Plasma bupivacaine levels were analyzed by high performance liquid chromatography
      with tandem mass spectrometry. RESULTS: Four males and 21 females, ASA I-II were
      enrolled in the present study. Mean age, body mass index, and serum albumin level
      were 69.9 +/- 5.95 years, 27 +/- 3.67 kg/m2, and 4.46 +/- 0.26 mg/dL,
      respectively. The median of peak plasma concentration was 538.35 ng/mL (min =
      176.30, max = 1,383.99) at 60 minutes after femoral nerve block, while the
      maximal plasma concentration of bupivacaine was 1,883.39 ng/mL at 10 minutes.
      None showed signs or symptoms of bupivacaine toxicity. CONCLUSION: Peak plasma
      concentrations of bupivacaine were demonstrated at 60 minutes after a single shot
      femoral nerve block, and no signs or symptoms of bupivacaine toxicity were
      observed Therefore, single shot femoral nerve block with 20 mL of 0.5%
      bupivacaine is safe.

PMID- 23539935
TI  - Optic atrophy after anti-vascular endothelial growth factor injection in diabetic
      patients with proliferative diabetic retinopathy.
AB  - OBJECTIVE: To study the prevalence of optic atrophy in patients with
      proliferative diabetic retinopathy (PDR) who underwent intravitreal bevacizumab
      injection and risk factors associated with optic atrophy. MATERIAL AND METHOD: A
      retrospective case control study enrolled 269 cases (394 eyes) of patients with
      PDR, in which 166 cases (219 eyes) received intravitreal bevacizumab injection.
      Associated factors such as type of DM, hemoglobin A1c level, hypertension,
      hypercholesterolemia, chronic kidney disease, previous intravitreal surgery
      retinal detachment, and vitreous hemorrhage were recorded. Criteria for diagnosis
      of optic atrophy were decreased visual acuity, pale optic disc and decreased
      nerve fiber layer thickness, which was measured by Stratus optical coherence
      tomography (OCT). The association between intravitreal bevacizumab injection and
      optic atrophy was analyzed by multiple logistic regression. RESULTS: Two hundred
      sixty nine patients with PDR, consisting of 166 patients with intravitreal
      bevacizumab injection and 103 cases without bevacizumab injection. Optic atrophy
      was found in 11.4% (25/219 eyes) and 8% (14/175 eyes) respectively. There was no
      evidence that intravitreal bevacizumab injection and associated systemic diseases
      were related to optic atrophy. The risk factor that was related to optic atrophy
      was previous intravitreal surgery (adjusted odds ratio (OR), 2.57 [95% CI, 1.13,
      5.84], p = 0.024). CONCLUSION: Anti-VEGF (bevacizumab) does not increase the risk
      of optic atrophy. The ophthalmologists should be aware of subsequent optic
      atrophy development in patients with PDR who undergo surgical intervention.

PMID- 23539936
TI  - Normal smell identification score and N-butanol threshold in Thai adults.
AB  - OBJECTIVE: To identify commonly recognized odorants and to find a normal
      threshold for n-butanol in Thai adults. MATERIAL AND METHOD: Eighty-one normal
      adult volunteers were enrolled between April and September 2010. They were asked
      to sniff from each glass bottle as long as they preferred. The threshold test was
      performed in an ascending method. Each volunteer was asked to identify the n
      butanol dilution bottle from two bottles of distilled water. Fifteen odorants
      available as commercial products were used for the identification test.
      Volunteers had to sniff each bottle and chose the answer from four choices.
      RESULTS: There were 33 male (40.7%) and 48 female (59.3%) volunteers. The mean
      age (+/- standard deviation) was 38.8 +/- 11.4 years, ranged from 22 to 60 years.
      The most common threshold bottle was number nine (40.7%). The most commonly
      recognized odorant was fish sauce (100%). The most intolerable odorant was
      ammonia (77.8%). The mean correct identification score (+/- standard deviation)
      was 13.6 +/- 1.4 odorants, ranged from six to 15 odorants. CONCLUSION: The
      present study showed commonly recognized odorants that could be used for an
      identification test and the normal n-butanol threshold in Thai adults.

PMID- 23539937
TI  - Sinonasal papilloma in Chiang Mai University Hospital.
AB  - OBJECTIVE: To study sinonasal papilloma patients in terms of clinical
      characteristics, treatment, outcome, and complications. MATERIAL AND METHOD: A
      retrospective descriptive study was done. Sinonasalpapilloma data were gathered
      between 1999 and 2009. There were 63 available patients from the 82 cases.
      RESULTS: There were nine cases of nasal papilloma (14.3%) and 54 of inverted
      papilloma (85.7%). The mean age of the inverted papilloma group was higher than
      the nasal papilloma group (54 +/- 12.97 years vs. 42.4 +/- 24.8 years). The most
      common symptom was unilateral nasal obstruction. There were three cases of
      synchronous malignancy in the inverted papilloma and two metachronous (9.3%).
      Thirty-nine patients (72%) could be followed-up for more than three months.
      Recurrence was more common in the inverted papilloma group than nasal papilloma
      (37% vs. 11.1%). The 50% recurrent time of the endoscopic group was 51 weeks and
      the external group was 14 weeks. The recurrence of the external approach group
      was 1.59 times the endoscopic group. Ten surgical complications were found in
      eight inverted papilloma patients (16%) and included three in the endoscopic and
      five in the external group. Most of them were minor They were hypoesthesia and
      epiphora. CONCLUSION: Sinonasal inverted papilloma was common, able to recur and
      associated with malignancy. Though this was a limited retrospective study, it
      showed lower recurrence on the endoscopic approach. The life-long follow-up is
      needed in all cases.

PMID- 23539938
TI  - Evaluation of pulmonary metastases in children by non-contrast chest computed
      tomography.
AB  - BACKGROUND: Most of the metastatic lung lesions are relatively high contrast in
      comparison to the lung background and easily detected in non-contrast enhancement
      chest computed tomography alone (NECCT). Pediatric patients may get benefit from
      its minimal radiation dose and lack of adverse reaction from iodinated contrast
      agent. OBJECTIVE: To compare effectiveness of non-contrast enhancement chest
      computed tomography (NECCT) in detecting thoracic metastasis with full protocol
      chest computed tomography (FPCCT) (chest computed tomography with and without
      contrast) in non-hematologic extrathoracic malignancy in children. MATERIAL AND
      METHOD: Both NECCT and FPCCT were evaluated in 50 pediatric patients with non
      hematologic extrathoracic malignancy retrospectively. Lung nodules, ground glass
      opacities, interlobular septal thickening, pleural effusion, pleural thickening,
      pericardial effusion, endobronchial lesion, and intravascular metastasis were
      evaluated separately on each CT protocol by two radiologists. RESULTS: Thirty
      boys and 20 girls were included in the present study (mean age = 10 years and 3
      months). The lesions include nodule (333 detected by NECCT (median = 3), 336
      detected by CECCT (median = 3)), ground glass opacity (12 detected by NECCT
      (median = 0), 15 detected by CECCT (median = 0)), interlobular septal thickening
      (12 detected by NECCT (median = 0), 11 detected by CECCT (median = 0)). There was
      100 percent match of calcified nodules (n = 36), pleural effusion (n = 1),
      pleural thickening (n = 3), intravascular thrombus (n = 2), and mediastinal lymph
      node (n = 1) between NECCT and FPCCT studies. There was no statistically
      significant different in capability of demonstrating all lesions between NECCT
      and FPCCT. Most of the discrepancies between NECCT and FPCCT were from motion
      artifact, inadequate inspiration, and radiologist's opinion rather than effect of
      contrast agent administration itself CONCLUSION: NECCT is as effective as FPCCT
      in evaluation of pulmonary metastasis in non-hematologic extrathoracic
      malignancies. For evaluation of lung metastases in this population, NECCT alone
      is sufficient.

PMID- 23539939
TI  - Focal fibrosis of the breast diagnosed by core needle biopsy under imaging
      guidance.
AB  - BACKGROUND: Focal fibrosis of the breast is an uncommon pathology, recognition of
      this lesion is important because it could mimic malignant lesions on both
      mammogram and ultrasonography (US). Concordance with the pathology result from
      core needle biopsy (CNB) and follow-up are essential to avoid false negative.
      OBJECTIVE: To characterize the mammographic and US features of focal fibrosis of
      the breast and to estimate the false negative rate for breast cancer when focal
      fibrosis was diagnosed by CNB. MATERIAL AND METHOD: The subjects were 82 patients
      diagnosed fibrosis of the breast by CNB during 7-year period. RESULTS: Of 38
      mammographic visible lesions there were mass lesions in 12 (32%), calcifications
      in 14 (37%), mass with calcifications in four (11%), architectural distortion in
      one (3%) and asymmetrical density in seven (18%). Most of the lesions seen on the
      US were hypoechoic mass (81%). The suspicious features, which warrant CNB,
      included irregular shape in 37 (55%), indistinct margin in 38 (57%), and
      posterior shadowing in 28 (42%). Most of the lesions were categorized as Breast
      Imaging Reporting and Data System (BI-RADS) 4A (59%). Thirteen cases underwent
      surgical biopsy and all showed benign pathologic results. No false-negative cases
      were detected. CONCLUSION: Focal fibrosis had some features similar to malignant
      lesion. CNB showed reliable pathological result. No false negative result was
      found in the present study.

PMID- 23539940
TI  - Ischemic cerebrovascular disease and calcified intracranial vertebrobasilar
      artery: A case-control study by using cranial CT.
AB  - OBJECTIVE: To evaluate the association of intracranial vertebrobasilar (VB)
      artery calcification and ischemic cerebrovascular disease of the posterior
      circulation. MATERIAL AND METHOD: A cross-sectional, retrospective, case-control
      study was performed in 198 patients with cranial CT Presence of the posterior
      fossa infarction was disclosed in 104 patients of the case group. Absence of the
      posterior fossa infarction in 94 patients were defined as a control group. They
      were age and sex matched. Circumferential and thickness of calcification was
      graded for the intracranial vertebral and basilar arteries. Association between
      vascular wall calcification and posterior fossa infarction was analyzed. RESULTS:
      No statistically significant relationship between the presence of VB
      calcification and posterior fossa infarction was found (p = 0.08, OR = 1.75, 95%
      CI = 0.94-3.26). In subgroup analysis, by re-classifying occipital lobe and
      thalamus as areas supplied by VB system, there was a statistically significant
      relationship between the VB calcification and infarction (p = 0.02, OR = 2.08,
      95% CI = 1.10-3.94). No relationship between degree of calcification and the area
      of infarction was observed. CONCLUSION: The present study showed no significant
      relationship between the VB artery calcification and ischemic infarction of
      cerebellum and brainstem, but a significant relationship between VBA
      calcification and infarction in the end territory of VBA supply.

PMID- 23539941
TI  - Oral health status of dementia patients in Chiang Mai Neurological Hospital.
AB  - OBJECTIVE: Investigate the oral health of patients with dementia and examine the
      association between the type and severity level of dementia on their dental
      caries sta tus. MATERIAL AND METHOD: Cross-sectional study conducted on
      outpatients referred to the memory clinic. Clinical examinations were based on
      WHO criteria. Socio-demographic data, functional ability, and dementia level were
      obtained from hospital medical records. The Thai version of the Mini Mental State
      Examination (MMSE-Thai 2002) was used as a cognitive testing instrument. The
      ability to perform oral care derived from an interview. RESULTS: Sixty-nine
      subjects were included in the present study. The mean age was 75.5 (+/- 7.0)
      years. Patients with Alzheimer's disease (AD) constituted the largest dementia
      group. More than half (60.9%), had dementia for less than two years and were
      functionally independent (66.7%). The majority (56.50%) had moderately severe
      dementia. More than half (52.50%) had at least 20 functional teeth. The mean
      number of teeth was 19.5 (+/- 8.4). Mean decayed, missing, and filled teeth
      (DMFT) were 14.9 (+/- 9.2). More than half (54.7%) had periodontal disease
      (pocket depth > or = 4 mm). Dementia severity was the only characteristic which
      showed a significant difference in dental caries experience (> or = 0.009).
      CONCLUSION: Dementia patients who attended the memory clinic had considerably
      better oral status compared to the national data. Dementia severity was the only
      characteristic that showed a significant difference in dental caries experience.

PMID- 23539942
TI  - Positive effects of Ska game practice on cognitive function among older adults.
AB  - BACKGROUND: Ska is a traditional board game in Thailand that involves high levels
      of cognition, planning, and decisionmaking. There have been no previous studies
      on the benefits of the Ska game as a cognitive function aid for older adults.
      OBJECTIVE: To examine the effects of Ska game practice on improving cognitive
      functioning among older adults. MATERIAL AND METHOD: Forty older adults living in
      the municipality of Phetchabun province, volunteered to take part in the present
      study. They were randomly selected and arranged into two intervention groups, an
      experiment and a control group (20 participants each group; 10 females and 10
      males). Each group was repeatedly trained as planned for at least 50 minutes per
      day, three sessions per week for the continuous duration of 16 weeks. The
      cognitive function measured in term of memory, Verbal Pair Association I and II
      (VPA I; VPA II), Visual Reproduction I and II (VR I; VR II), the attention used
      of Trail Making Test part A (TMT-A), and the executive function used by means of
      the Wisconsin Card Sorting Test (WCST). The examination was done by a clinical
      psychologist and a medical technologist using neurotransmitter to measure
      Acetylcholinesterase (AChE) activity, before and after the intervention. The
      independent variables were measured with t-test to compare the mean scores of two
      different groups and between males and females of the Ska group. The level of
      significance considered was p < 0.05. RESULTS: The findings revealed that those
      who joined the Ska group reported statistically significant better scores of
      cognitive function in memory, attention, executive function from VPA I, VPA II,
      VR I, VR II, TMT-A, and WCST compared to those who were in the control group (p <
      0.05). However, there was no significant difference of AChE activity between the
      Ska and the control group (p > 0.05). In addition, there was no significant
      difference mean in cognitive function between male and female Ska group (p > or =
      0.05). CONCLUSION: Finding shows that the Ska game could enhance the cognitive
      functioning in terms of memory, attention, and executive function in older
      adults.

PMID- 23539943
TI  - Thai health education program for improving TB migrant's compliance.
AB  - OBJECTIVE: Investigate the effectiveness of health education programs by using
      the PRECEDE-PROCEED Model to improve non-Thai migrant TB patient's compliance
      during treatment. MATERIAL AND METHOD: This quasi-intervention study was
      conducted in three targeted hospitals, between August 2009 and December 2010. The
      study sample consisted of 100 cases, 50 cases who registered in Samutsakorn
      Province served as the intervention group and 50 cases who registered in
      Samutprakarn Province served as the control group. RESULTS: At the end of the
      health education intervention, the intervention group showedsignificantly
      improved health-behavior scores in nine domains-health promotion, health
      education, predisposing, reinforcing, enabling factors, behavior and lifestyle,
      environment, and health status, which were also significantly higher than the
      control group (p < 0.001). The percentage of patients achieving successful
      treatment outcomes was 76% in the intervention group and 62% in the control
      group. CONCLUSION: The tuberculosis treatment and care program, and the
      associated health education interventions enabled migrants to complete the
      treatment regimen and achieve treatment success. It could also help TB staff
      develop an appropriate program and clear understanding of TB control among
      migrants. It is recommended that this type of information and health education
      program be used in other hospitals and healthcare settings providing TB services
      for migrants throughout the nation.

PMID- 23539944
TI  - Early onset and rapid progression of glaucoma in a neonate with Sturge-Weber
      syndrome.
AB  - Sturge-Weber syndrome (SWS) is an uncommon neurocutaneous syndrome usually
      presenting with a triad of cutaneous, neurological, and ophthalmological
      symptoms. The cutaneous lesion can be observed at birth in most cases while the
      symptoms of the nervous and ocular systems involvement usually appear later in
      life. The most common ocular manifestation in SWS is glaucoma, which can occur in
      the early-life period. The authors reported a case of SWS in which the symptoms
      of glaucoma rapidly developed within two weeks following an ophthalmologic
      evaluation that was initially negative at the age of one week.

PMID- 23539945
TI  - Primary angiosarcoma of the breast: a case report and review of the literature.
AB  - Primary angiosarcoma of the breast is rare. Therefore, no randomized trial can be
      used as guideline for diagnosis and treatment. To achieve optimal outcome,
      previous reports of case series are the sources for management with expected long
      term survival. The objective of the present case report is to demonstrate
      complete pathologic response to neoadjuvant taxanes without recurrence after two
      years of follow-up.

PMID- 23539946
TI  - Evaluation of anti-leishmanial effects of killed Leishmania vaccine with BCG
      adjuvant in BALB/c mice infected with Leishmania major MRHO/IR/75/ER.
AB  - There are many strategies to control leishmaniasis, but majority of them are
      inadequate. Killed Leishmania vaccine (KLV) has been applied for its
      immunogenicity in human and mouse model. Bacillus Calmette-Guerin (BCG) as
      adjuvant is an immune-modulator inducing humoral and cellular immune responses
      during zoonotic cutaneous leishmaniasis (ZCL). Both KLV and BCG have been applied
      for their immune responses in hosts for controlling leishmaniasis. In this study,
      KLV and BCG were applied to inhibit replication and visceralization of Leishmania
      major in BALB/c mice. Mice were injected with KLV and BCG, followed by infection
      with promastigotes of L. major. Six weeks after infection, a small nodule
      appeared, which was followed by development of a large lesion and
      visceralization. Effects of KLV and BCG, physiopathological changes, lesion size,
      delay of lesion formation, proliferation of amastigotes inside macrophages and
      detection of amastigotes in target organs were studied. Results showed that the
      KLV had anti-leishmanial activity by reducing lesion size on late infection. In
      KLV and BCG group, the average number of amastigotes in macrophages was lower
      than in other groups. Significant reductions in number of amastigotes in both
      spleen and lymph node were observed, indicating lower visceralization of
      Leishmania parasites in these target organs. No significant changes were
      presented in body weights, survival rates and degrees of splenomegaly in test
      group. It can be concluded that application of KLV and BCG had acceptable
      efficacy in reduction of skin lesions size and proliferation of parasites, even
      though a few side-effects were observed. It is indicated that KLV/BSG may have
      ability to modulate host immune responses against Leishmania parasites and to
      reduce pathophysiology of the disease during infection.

PMID- 23539947
TI  - A digenean parasite in a mudskipper: Opegaster ouemoensis sp. n. (Digenea:
      Opecoelidae) in Periophthalmus argentilineatus Valenciennes (Perciformes:
      Gobiidae) in the mangroves of New Caledonia.
AB  - Opegaster ouemoensis sp. n. is described from Periophthalmus argentilineatus
      Valenciennes (Gobiidae). Distinctive features included the weak or undetectable
      papillae of the ventral sucker and the small, but distinct cirrus-sac. The new
      species is compared with 25 marine species of Opegaster for which a table of
      measurements and ratios is presented. The new combination Opegaster
      queenslandicus (Aken'Ova, 2007) (originally in Opecoelus) is formed. Fifteen
      mudskippers were intensively examined for parasites; larval anisakid nematodes
      and acanthocephalans were found, but no monogeneans, cestodes, copepods, isopods,
      hirudineans or adult nematodes. A brief summary of the helminth parasites of
      mudskippers is included.

PMID- 23539948
TI  - Cardicola langeli sp. n. (Digenea: Aporocotylidae) from heart of sheepshead,
      Archosargus probatocephalus (Actinopterygii: Sparidae) in the Gulf of Mexico,
      with an updated list of hosts, infection sites and localities for Cardicola spp.
AB  - Cardicola langeli n. sp. (Digenea: Aporocotylidae) infects the heart of
      sheepshead, Archosargus probatocephalus (Walbaum, 1792) (Perciformes: Sparidae)
      in the northern Gulf of Mexico off Horn Island (type locality), Mississippi, USA.
      The new species is described herein using light and scanning electron microscopy
      of adult specimens and can be most easily distinguished from the other 24
      accepted species of Cardicola Short, 1953 by the combination of having (i) an
      ovovitelline duct that extends anteriad and that (ii) is posterior to the ootype,
      (iii) a male genital pore that is lateral to the oviducal seminal receptacle and
      (iv) a female genital pore lateral to the ootype. The new species is the only
      member of Cardicola so-far reported to have tegumental spines that are distally
      flattened and broad, rather than pointed. The new species generally resembles the
      two other species of Cardicola that infect sparids, i.e. Cardicola cardiocolum
      (Manter, 1947) (type species) from jolthead porgy, Calamus bajonado (Block et
      Schneider), in the Gulf of Mexico and Cardicola aurata Holzer, Montero, Repulles,
      Sitja-Bobadilla, Alvarez-Pellitero, Zarza et Raga, 2008, from gilthead seabream,
      Sparus aurata Linnaeus, in the Mediterranean Sea, by having a spheroid anterior
      sucker with concentric rows of minute spines anterior to the mouth and by having
      a similar general arrangement of the vitellarium, gonads and genitalia. However,
      it differs from them by having the combination of the aforementioned five
      features plus asymmetrical posterior caeca and a dextral posterior caecum that
      extends beyond the posterior margin of the ovary. Probable eggs of C. langeli n.
      sp. that contain a ciliated miracidium infect gill epithelium and are spheroid.
      An updated list of hosts, infection sites and geographic localities for the 25
      accepted species of Cardicola is provided.

PMID- 23539949
TI  - Induction of prominent Th1 response in C57Bl/6 mice immunized with an E. coli
      expressed multi T-cell epitope EgA31 antigen against Echinococcus granulosus.
AB  - First step in developing an epitope-based vaccine is to predict peptide binding
      to the major histocompatibility complex (MHC) molecules. We performed
      computational analysis of unique available EgA31 sequence to locate appropriate
      antigenic propensity positions. T-cell epitopes with best binding affinity values
      of < 50% inhibitory concentration were selected using different available servers
      (Propred and IEDB). Peptides with 100% population coverage were selected. A DNA
      fragment corresponding to the furin linker enriched in Golgi apparatus was
      inserted sequentially between each epitope sequences in a synthetic DNA in order
      to cleave the chimeric protein into four separated peptides. Subsequently, the
      synthetic DNA was cloned into the pGEX4T-1 and pEGFP-N1 vectors and GST-ChEgA31
      was expressed in E. coli strain BL21-DE3. The recombinant protein was detected by
      western blotting using an HRP-conjugated polyclonal anti-GST antibody. Fusion
      protein purified by affinity chromatography was used to raise antisera in
      rabbits. Results in agar gel immunodiffusion assay indicated induction of
      specific antibodies against multiepitope antigen in the tested rabbits. Cytokine
      assay was carried out in C57Bl/6 mice and the levels of cytokines were analyzed
      by sandwich ELISA. Interestingly, production of specific IFN-gamma was
      prominently higher in mice immunized with GST-ChEgA31 and pEGFP-ChEgA31 (650-1300
      pg/ml) compared to control groups. No difference was observed in the level of IL
      10 and IL-4 in immunized and GST control group. Challenge study with 500 live
      protoscolices of Echinococcus granulosus on immunized mice demonstrated
      protectivity level (50-60%). Based on our results, it appeared that the chimeric
      protein in the study was able to stimulate T-helper cell-1 (Th1) development and
      high level of cell mediated immunity in mice.

PMID- 23539950
TI  - First description of adults of the type species of the genus Glossocercus
      Chandler, 1935 (Cestoda: Gryporhynchidae).
AB  - The type species of the genus Glossocercus Chandler, 1935, G. cyprinodontis
      Chandler, 1935, was described as metacestode (larval stage) from the mesentery of
      the sheepshead minnow fish (Cyprinodon variegatus Lacepede) from Galveston Bay,
      Texas. The description was based on the morphology of the rostellar hooks;
      however, the features of the internal morphology of the proglottides could no be
      provided. In the present study we describe for the first time the features of the
      adult G. cyprinodontis from the intestine of Pelecanus occidentalis Linnaeus,
      Nycticorax nycticorax Linnaeus and Egretta rufescens Gmelin in Mexico.
      Glossocercus cyprinodontis possesses similar strobilar morphology with the two
      other congeneric species, both distributed in the Neartic and Neotropical
      regions, i.e. Glossocercus caribaensis (Rysavy et Macko, 1971) and Glossocercus
      auritus (Rudolphi, 1819). However, G. cyprinodontis differs mainly in the shape
      of the rostellar hooks (those of G. cyprinodontis possess the handle and the
      guard strongly sclerified compared to those of G. auritus and G. caribaensis) and
      their size (total length of 175-203 microm in G. cyprinodontis compared to 189
      211 microm in G. caribaensis and 220-285 microm in G. auritus). Generic diagnosis
      of Glossocercus is emended: rostellar hooks in two rows with ten hooks of
      different shape and length in each, scolex large and globular, proglottides
      craspedote, wider than long, genital pores irregularly alternating, vagina
      transverse, surrounded by epithelial cells, ventral to cirrus-sac, uterus bar
      shaped in mature proglottides, occupies all space between osmoregulatory ducts
      with eggs in gravid proglottides, ovary lobed in middle of proglottis, cirrus-sac
      elongate, between osmoregulatory canals, cirrus armed with spinitriches and
      apical tuft of slender spinitriches.

PMID- 23539951
TI  - A reinvestigation of spermiogenesis in Amphilina foliacea (Platyhelminthes:
      Amphilinidea).
AB  - Spermiogenesis in the amphilinidean cestode Amphilina foliacea (Rudolphi, 1819)
      was examined using transmission electron microscopy. The orthogonal development
      of the two flagella is followed by a flagellar rotation and their proximodistal
      fusion with the median cytoplasmic process. This process is accompanied by
      extension of both the mitochondrion and nucleus into the median cytoplasmic
      process. The two pairs of electron-dense attachment zones mark the lines where
      the proximodistal fusion of the median cytoplasmic process with the two flagella
      takes place. The intercentriolar body, previously undetermined in A.foliacea, is
      composed of three electron-dense and two electron-lucent plates. Also new for
      this species is the finding of electron-dense material in the apical region of
      the differentiation zone at the early stage of spermiogenesis, and the fact that
      two arching membranes appear at the base of the differentiation zone only when
      the two flagella rotate towards the median cytoplasmic process. The present data
      add more evidence for a close relationship between the Amphilinidea and the
      Eucestoda.

PMID- 23539952
TI  - DNA-barcoding contradicts morphology in quill mite species Torotrogla merulae and
      T. rubeculi (Prostigmata: Syringophilidae).
AB  - Torotrogla merulae Skoracki, Dabert et Ehrnsberger, 2000 and T. rubeculi
      Skoracki, 2004 have been considered as distinct steno- and monoxenous quill mite
      species (Acari: Prostigmata: Syringophilidae) parasitizing the thrushes of the
      genus Turdus Linnaeus and the European robin Erithacus rubecula (Linnaeus),
      respectively. Morphological and molecular studies on the taxonomical status of
      these two species provided contradictory results. Well defined differences in
      morphology were not supported by substantial genetic distance in nucleotide
      sequences of the DNA barcode (mitochondrial cytochrome c oxidase subunit I, COI,
      and D2 domain of the nuclear 28S rRNA gene), by the topology of the phylogenetic
      trees (neighbor-joining, maximum parsimony, maximum likelihood) and the network
      analyses of the COI haplotype genealogy (median-joining, statistical parsimony)
      that reveal rubeculi populations nested within merulae haplotypes. Since detected
      differences between T. merulae and T. rubeculi populations (1.6-2.4% for COI and
      0.1% for D2) are comparable to the intraspecific level observed in majority of
      currently recognized European Torotrogla species and are much lower than the
      interspecific distances observed in the genus, we postulate their conspecificity.
      Because main morphological distinctions concern the structures used for feeding,
      we hypothesize that they are the result of phenotypic plasticity evoked by
      specific and different environmental conditions prevailing on the host bodies
      (thickness of the feather quill wall).

PMID- 23539953
TI  - The genus Hatschekia (Copepoda: Hatschekiidae) from pufferfishes
      (Tetraodontiformes: Tetraodontidae) off the Ryukyu Islands, Japan, with
      descriptions of four new species and a redescription of H. pholas.
AB  - Four new species of the genus Hatschekia Poche, 1902 (Copepoda:
      Siphonostomatoida: Hatschekiidae) are described based on female specimens
      collected from pufferfishes (Tetraodontiformes: Tetraodontidae) caught in coastal
      waters off the Ryukyu Islands, Japan: H. longiabdominalis sp. n. on Arothron
      hispidus (Linnaeus), H. geniculata sp. n. on A. hispidus (type host) and A.
      stellatus (Bloch et Schneider), H. ellipsocorpa sp. n. on A. mappa (Lesson), and
      H. boonah sp. n. on A. nigropunctatus (Bloch et Schneider) (type host) and A.
      meleagris (Schneider). Hatschekia longiabdominalis sp. n. and H. boonah sp. n.
      differ from all other congeners by sharing an unusual, projected abdomen and a
      fusiform trunk with posterior lobes; these two species are differentiated from
      each other by the shape of the dorsal chitinous frame on the cephalothorax.
      Hatschekia geniculata sp. n. can be distinguished by the combination of the
      following morphological characters: a rhomboidal cephalothorax with a pair of
      lateral conical protrusions, a cylindrical trunk with posterior lobes and a bent
      abdomen with a dorsal protrusion. Hatschekia ellipsocorpa sp. n. resembles H.
      pholas (Wilson, 1906) but can be distinguished from the latter by the possession
      of one distal and one inner setae on the terminal endopodal segment of legs 1 and
      2. Hatschekiapholas is also redescribed based on female specimens from the
      tetraodontid A. stellatus. At present, 44 nominal species of the genus have been
      reported from Japan, including four new species described in this paper; 38 of
      them have been described originally from Japan.

PMID- 23539954
TI  - Trafficking of Plasmodium falciparum chimeric rhoptry protein with Brefeldin A.
AB  - Trafficking of the rhoptry chimeric protein RhopH2-GFP, which contains RhopH2
      signal peptide plus the downstream five amino acids, was dissected by treating
      parasites with Brefeldin A at three different time points. Twenty eight hrs-stage
      trophozoites accumulated the chimera within the parasite endoplasmic reticulum.
      In 32 hrs-stage schizonts, the chimera was distributed in the parasite cytoplasm
      but not in the parasitophorous vacuole. In 36 hrs stage-schizonts, the chimera
      was detected in individual structures around the developing merozoites and, in
      contrary to non-treated parasites, no immature rhoptry vesicles could be detected
      in the cytoplasm of immature merozoites. These data show that this chimera is
      trafficked to the rhoptries via Brefeldin A-sensitive pathway indicating that
      this trafficking is similar to that of the endogenous rhoptry proteins, and that
      the five amino acids downstream of the signal peptide cleavage site may contain
      the sorting signal required for rhoptry targeting.

PMID- 23539955
TI  - [Clinical analysis of 1059 patients with taste disorders].
AB  - Taste disorders are caused by several factors, and there have been few reports
      concerning the clinical course of taste disorders. In this study, patients with
      taste disorders were classified into 10 groups according to causes, and they were
      retrospectively studied in terms of therapeutic effects. In total, 1059 patients
      (412 men and 647 women, mean age: 60.0 years) who complained of taste disorders
      were reviewed in our clinic. The patients were asked detailed questions about
      their history of symptoms, and their emotional status was assessed using a self
      rating depression scale. In all subjects, taste functions were measured by
      electrogustometry (EGM) and filter paper disks (FPD). The grades of their
      symptoms were assessed with a visual analogue scale (VAS). In addition, the
      levels of serum iron, copper, and zinc were examined. The patients were treated
      with zinc sulfate, polaprezinc, iron preparation, herbal medicine, and minor
      tranquilizers according to the factors causing the taste disorders. The most
      frequent cause was idiopathic taste disorder (192 cases, 18.2%), the second was
      psychogenic (186 cases, 17.6%), and the third was drug-induced (179 cases,
      16.9%). The recovery rate of the symptoms was 64/92 (70.2%) in post-common cold,
      31/35 (88.6%) in iron deficiency, and 85/116 (73.3%) in zinc deficiency. In these
      groups, the rates of recoveries were better than in the other groups. The
      recovery period in drug-induced taste disorders was approximately twice as long
      as the recovery period in the other groups. In the patients who were able to
      start treatment within 6 months from the onset of taste disorder, the recovery
      rate was significantly higher and the therapeutic period was significantly
      shorter than in those who had the disorders for more than 6 months (p<0.05,
      respectively).

PMID- 23539956
TI  - [Evaluation of hearing results after tympanoplasty according to the
      classification of the development degree for pars flaccid cholesteatoma].
AB  - Our surgical treatment for middle ear cholesteatoma is based on the following 2
      concepts: (1) Preservation of the physiological morphology and function of the
      middle ear, that is, maximal preservation of the posterior wall of the external
      auditory meatus and the middle ear mucosa and (2) Careful resection of the matrix
      membrane of the cholesteatoma through the continuity of the matrix membrane. In
      case the cholesteatoma matrix membrane is ruptured, a staged operation should be
      performed to prevent the development of residual cholesteatoma from the residual
      matrix. In this study, we classified a total of 238 cases of the pars flaccida
      cholesteatoma primary operated on Osaka Red Cross Hospital between January 2006
      and March 2008 according to the Classification and Staging of Cholesteatoma
      proposed in 2010. The age of the patients ranged from 4 to 79 years (average:
      49.8 years) and there were 123 males and 115 females. Follow up ranged from 1
      year to 5 years with a mean follow-up period of 47.8 months. Regarding the stage,
      38 (16.0%) ears had stage I cholesteatoma, 155 (65.1%) ears had stage II, and 45
      (18.9%) ears had stage III. The successful outcome rate was 97.4% for stage I,
      78.7% for stage II and 60.0% for stage III. The rate of the residue and the
      postoperative recurrence was 2.5% and 4.2%.

PMID- 23539957
TI  - [Two cases of pediatric psychogenic gait disturbance].
AB  - We report herein on 2 cases of pediatric psychogenic gait disturbance. Both
      patients (boys) were aged 10 years. Patient 1 had psychogenic fever and
      psychogenic visual disturbance. His symptoms improved after 4 months. Patient 2
      had headache and general fatigue and was subfebrile. His symptoms disappeared
      after 5 months. Pediatric psychogenic gait disturbance is rare, and it is
      important to understand the clinical characteristics of the affected patients. In
      most cases, treatment can be time-consuming. To treat these patients, it is
      important to rule out organic disorders. A diagnosis of psychogenic gait
      disturbance should be made on the basis of the clinical characteristics of the
      disorder, such as (1) momentary fluctuations of stance and gait, often in
      response to suggestions; (2) excessive slowness or hesitation of locomotion
      incompatible with neurological disease; and (3) uneconomic postures with wastage
      of muscle energy. These symptoms typically improve in 4-5 months.

PMID- 23539958
TI  - [Treatments for otorhinolaryngological patients with psychiatric disorders].
AB  - There are few systems in place for patients with psychiatric disorders who need
      treatments for physical complications. In Tokyo, "The Tokyo metropolitan
      psychiatric emergency system" was established in 1981, and Ome Municipal General
      Hospital participated in it. Under this system, fifteen patients with psychiatric
      disorders were treated for otorhinolaryngological diseases in our department from
      April 2005 to March 2011. We reviewed the fifteen patients. The coexisting
      psychiatric disorders were schizophrenia in twelve patients, and mental
      retardation, Korsakoff's syndrome, and Alzheimer's dementia in one patient each,
      respectively. All the patients had been receiving psychiatric treatment. The
      otorhinolaryngological diseases were head and neck cancer in nine patients,
      chronic sinusitis in three patients, and benign salivary gland tumor,
      cholesteatoma, and epistaxis in one patient each, respectively. Among the fifteen
      patients, thirteen could complete their treatment, but two dropped out due to
      exacerbation of their psychiatric symptoms. The therapeutic course is uncertain
      in otorhinolaryngological diseases occurring concomitantly with psychiatric
      disorders, especially in head and neck cancer, because it may be difficult to
      prioritize the problem when determining the treatment options and delivering the
      treatment. Thus, we should treat patients with psychiatric disorders carefully on
      a case-by-case basis depending on their psychiatric symptoms. It is also
      important to cooperate with psychiatrists and patients' families.

PMID- 23539959
TI  - [Physiological functions of hydrogen sulfide (H2S) and its therapeutic
      applications].

PMID- 23539960
TI  - [Regulation of cellular functions by Elongin BC based E3 ubiquitin ligase].

PMID- 23539961
TI  - [New aspects on tRNA-type splicing].

PMID- 23539962
TI  - [Autophagy as a host defense against the intracellular microbe infection].

PMID- 23539963
TI  - [Mediator lipidomics revealed novel roles of eosinophils in the resolution of
      inflammation].

PMID- 23539964
TI  - [Roles of myosin II regulatory light chain at the constricting area of dividing
      cells].

PMID- 23539966
TI  - History and excellence.

PMID- 23539965
TI  - [Slp2-a transports the apical signaling molecule podocalyxin to the apical
      surface and affects cell-cell interactions].

PMID- 23539967
TI  - Whiter than white?

PMID- 23539968
TI  - A century of dental education: the Cork University Dental School and Hospital,
      1913-2013.

PMID- 23539969
TI  - Prevention of sports-related injuries.

PMID- 23539970
TI  - Dental implants and single implant-supported restorations.
AB  - Replacing missing teeth using dental implants is a good treatment option with a
      high degree of success. As the dental implantology field develops and the number
      of implants placed worldwide increases, several terms and techniques have been
      formulated. Therefore, a basic knowledge of dental implants is necessary for
      every dental student and dentist. The current article sheds light on how the
      dental implant integrates with its surrounding bone and what factors can affect
      this integration. The relationship between the implant and its surrounding soft
      tissue, different types of the dental implants, and the restorative components
      and procedures, are all reviewed.

PMID- 23539971
TI  - Brighten up.

PMID- 23539972
TI  - Caring for people is NZNO's first duty.

PMID- 23539973
TI  - End of Life Choice Bill raises social dilemmas.

PMID- 23539974
TI  - Inaccuracies in news report.

PMID- 23539975
TI  - Author reply: To PMID 23409493.

PMID- 23539976
TI  - New president promises she is value for money.

PMID- 23539977
TI  - Tougher requirements for overseas trained nurses to register here.

PMID- 23539978
TI  - Nurses subjected to sexualised verbal abuse.

PMID- 23539979
TI  - NZNO members stand up against family violence.

PMID- 23539980
TI  - Pursuing the dream of flying and nursing.

PMID- 23539981
TI  - Canterbury DEUs foster collegiality.

PMID- 23539982
TI  - Community DEU empowers students and staff.

PMID- 23539983
TI  - Jaundice: an excess of bilirubin.

PMID- 23539984
TI  - Student nurse let loose on the wards.

PMID- 23539985
TI  - Recognising and valuing preceptors.

PMID- 23539987
TI  - Seeking support during a competence review.

PMID- 23539986
TI  - Seeking answers to perioperative deaths.

PMID- 23539988
TI  - Local home-care provider ousted.

PMID- 23539989
TI  - Nurse's registration cancelled for fraudulent acts.

PMID- 23539990
TI  - "HCA regulation would be game changer for care".

PMID- 23539991
TI  - New local pay treat looms.

PMID- 23539992
TI  - "We must understand fallibility and develop moral resilience".

PMID- 23539993
TI  - Bad apple nurses needs to be named and shamed. Interview by Sarah Calkin.

PMID- 23539994
TI  - "Professionalism is the best regulator of nursing care".

PMID- 23539995
TI  - Tackling communication challenges in dementia.
AB  - Nurses and other healthcare workers are often anxious about communicating with
      people who are living with dementia. This article discusses the issues involved
      and describes communication techniques taken from the Talking Toolkit, which was
      developed by Bupa to provide strategies for communicating in a meaningful way
      with people who have dementia. Since we live in an ageing society where
      increasing numbers of people are being diagnosed with Alzheimer's disease and
      other forms of dementia, such strategies for communication are increasingly
      relevant for all nurses and health workers.

PMID- 23539996
TI  - Leading culture change to improve dementia care.
AB  - This article discusses elements that contribute to ownership in dementia care,
      which, in turn, can add to our understanding of what dementia leadership is. A
      training programme--the Dementia Leadership Award--aimed at care-home owners,
      managers and clinical leads throughout Gloucestershire is creating a person
      centred, staff-centred work environment. The approach is bringing about a shift
      in culture whereby managers of care homes and other personnel understand the
      importance of the dementia link worker role, support the advanced training these
      team members undertake, and appreciate their own significant impact on the
      quality of care delivered to people with dementia.

PMID- 23539997
TI  - A guide to creating a dementia-friendly ward.
AB  - Admission to hospital can be distressing for people with dementia, but
      appropriately designed surroundings can reduce this. This article explains how
      simple adaptations to the ward environment can improve the quality of care they
      receive.

PMID- 23539998
TI  - Conducting interviews with failing students.
AB  - Pre-registration students are bound by the Nursing and Midwifery Council's code
      of conduct, and must meet the expectations for performance laid out in the NMC's
      standards for competence. When a student is not achieving the relevant
      competencies and is regarded as at risk of failing a clinical placement, it is
      paramount that the mentor acts promptly, bringing forward interim interviews
      where appropriate. Good interview technique will help mentors and students to
      address difficulties in placements. Mentors should receive adequate support to
      address problems during the remainder of the student's placement or, if a student
      does not reach the required level of competency or professional behaviour, ensure
      that they do not pass.

PMID- 23539999
TI  - 60 second with Thomas Currid. Interview by Eileen Shepherd.

PMID- 23540001
TI  - Coach your team to success.

PMID- 23540000
TI  - Advice patients can trust.

PMID- 23540002
TI  - Inside the MASH. Part 2.

PMID- 23540003
TI  - Skin changes during pregnancy. Part 2: rash decision?

PMID- 23540004
TI  - Paying attention: Psychosocial interventions for ADHD.

PMID- 23540005
TI  - A topic in 10 questions: Managing infantile colic.

PMID- 23540006
TI  - The developing role of probiotics in infant and maternal health.

PMID- 23540008
TI  - Early years childcare ratios 'relax' in England.

PMID- 23540007
TI  - At a glance: Febrile convulsion in children.

PMID- 23540009
TI  - Drinks companies cut sugar content.

PMID- 23540010
TI  - NHS spending squeeze will lead to rises in abortion and STI rates.

PMID- 23540011
TI  - Health visiting in Scotland risks becoming 'unsustainable'.

PMID- 23540012
TI  - Francis delivers his verdict.

PMID- 23540013
TI  - Causing a stir. Interview by Louise Naughton.

PMID- 23540014
TI  - Multidisciplinary workshops: learning to work together.
AB  - Health and social care professional practice needs to move with the times and to
      respond to the ever-changing combination of health needs, economic realities and
      health-policy imperatives. A clear understanding of the variety of forces at play
      and the ability to marshal these to good effect by working in partnership with
      multidisciplinary colleagues and children/families is a must, not least in this
      time of economic austerity and ever-rising health inequalities, when vulnerable
      children's lives and complex family relationships and behaviours so easily become
      increasingly strained and challenged. This sad reality calls out for relevant
      joined-up solutions by all participants--an agenda so often called into question
      by court judgement after court judgement. The multidisciplinary workshops to be
      discussed have developed and changed over the past decade and provide a safe but
      realistic learning environment for students from health and social care
      backgrounds to experience the difficulties and barriers to good multidisciplinary
      working, to better understand others' perspectives and activities and consider
      and develop new and better practical strategies for working with
      multidisciplinary professional colleagues, children and families. All of the
      workshops are underpinned by specific discipline-focused theoretical work.

PMID- 23540015
TI  - Assessing the mental health and wellbeing of the lesbian, gay, bisexual and
      transgender population.
AB  - Health needs assessment is a fundamental tool in public health practice. It
      entails the identification of needs from a range of perspectives, including
      epidemiological data, the views of local and professional people, and the
      comparative needs of the group under consideration. This paper describes the
      process undertaken with the lesbian, gay, bisexual and transgender (LGBT)
      population of an area in the north-east of England. The findings were used to
      inform and influence commissioners and service providers about services and
      interventions that will address these needs, and bring about better emotional and
      mental health and wellbeing as identified by LGBT people themselves. Research
      shows that there are great inequalities in the experience of these groups when
      compared with the heterosexual population. This was confirmed by the local LGBT
      communities. Consultation with the LGBT population showed that they experience
      ongoing stigma and discrimination, despite the greater apparent acceptance of
      diversity within the community. Recommendations were identified, which
      particularly focus on increasing the visibility of these groups, highlighting
      training issues and addressing generic or specialist services, in order to reduce
      discrimination.

PMID- 23540016
TI  - What constitutes safeguarding children supervision for health visitors and school
      nurses?
AB  - Safeguarding children supervision is an essential requirement for the
      professional development of health visitors and school nurses. Supervision is
      dedicated time for the discussion of individual cases of concern about
      safeguarding children. It is considered to be best practice in the development of
      knowledge, skills and competencies. The aim of this article is to critically
      examine the available literature on what constitutes safeguarding supervision.
      The overall objective of the article is to examine and define safeguarding
      supervision in relation to both health visitors and school nurses. This
      literature review analyses and evaluates available literature with regards to
      safeguarding children supervision.

PMID- 23540017
TI  - Use your voice: speak up for your clients.

PMID- 23540018
TI  - Vitamin D deficiency in at-risk groups.
AB  - There has been a lot of public health interest in vitamin D since the documented
      resurgence of rickets in children, the identification of widespread vitamin D
      deficiency and the growing understanding of the role vitamin D plays in the
      immune system. Some people are at greater risk of vitamin D deficiency than
      others, including babies and individuals of Asian and Black origin. This article
      looks at two particular aspects of vitamin D deficiency risk: skin colour and the
      relationship with regards to vitamin D status between the mother and infant at
      birth and through breastfeeding. The aim of this article is to enable the
      practitioner to confidently identify mothers and babies at increased risk of
      vitamin D deficiency.

PMID- 23540019
TI  - Mileage allowances: the new scheme.

PMID- 23540020
TI  - Transitions in the new year.

PMID- 23540021
TI  - Taking the first steps to serving on a board.

PMID- 23540022
TI  - Colorado public health nurses: making a difference in the communities--and
      beyond.

PMID- 23540023
TI  - [TBE (tick-borne encephalitis) in childhood--is it dangerous?].

PMID- 23540024
TI  - [Our meat consumption--a "sacred cow"].

PMID- 23540025
TI  - [Modern imaging provides problematic incidental finding. Premalignant changes
      puts the patient's interest against national economy].

PMID- 23540026
TI  - [Loperamide prescribed too rarely in tourist diarrhea. Results from survey for
      infectious disease physicians].

PMID- 23540027
TI  - [Biostatistics has a central role in epidemiology. Introduction to concepts and
      methods from clinical observational studies].

PMID- 23540028
TI  - [A challenge for health care and society].

PMID- 23540029
TI  - [Affective syndromes are fatal--the risk of suicide is high].

PMID- 23540030
TI  - [Depression from cradle to grave].

PMID- 23540031
TI  - [Distinguishing between depression and chronic fatigue syndrome].

PMID- 23540032
TI  - [Bipolar disorder--a psychiatric core illness].

PMID- 23540033
TI  - [Specialized outpatient care--effective in affective disorders].

PMID- 23540034
TI  - [Depression treatment--then, now and in the future].

PMID- 23540035
TI  - [The need for disaster scenario training in Swedish hospitals should not be
      underestimated].

PMID- 23540036
TI  - [Quality registries--a well dressed popular movement].

PMID- 23540037
TI  - [Quality registers--one of many tools].

PMID- 23540038
TI  - [Evaluation of the rehabilitation guarantee requires better scientific support].

PMID- 23540040
TI  - Performance improvement in health care.

PMID- 23540039
TI  - [The father of botany on the flora of mental disorders].

PMID- 23540041
TI  - A management, leadership, and board road map to transforming care for patients.
AB  - Over the last decade I have studied 115 healthcare organizations in II countries,
      examining them from the boardroom to the patient bedside. In that time, I have
      observed one critical element missing from just about every facility: a set of
      standards that could reliably produce zero-defect care for patients. This lack of
      standards is largely rooted in the Sloan management approach, a top-down
      management and leadership structure that is void of standardized accountability.
      This article offers an alternative approach: management by process--an operating
      system that engages frontline staff in decisions and imposes standards and
      processes on the act of managing. Organizations that have adopted management by
      process have seen quality improve and costs decrease because the people closest
      to the work are expected to identify problems and solve them. Also detailed are
      the leadership behaviors required for an organization to successfully implement
      the management-by-process operating system and the board of trustees' role in
      supporting the transformation.

PMID- 23540042
TI  - Pursuing the perfect patient experience.
AB  - Adapting the principles and tools of the Toyota Production System to healthcare
      in the form of the Virginia Mason Production System has enabled Virginia Mason
      Medical Center to transform itself as an organization. Virginia Mason has worked
      persistently for more than a decade to apply Toyota methods to eliminate waste,
      improve safety and quality, and provide the community it serves with the highest
      quality healthcare at the lowest cost. We have made great progress in this
      pursuit.

PMID- 23540043
TI  - Adapting to the new healthcare market.

PMID- 23540044
TI  - High reliability: truly achieving healthcare quality and safety.

PMID- 23540045
TI  - Making lean progress last: why sustaining excellence requires the right
      leadership framework.

PMID- 23540047
TI  - Outbreak news. Poliomyelitis, Niger.

PMID- 23540046
TI  - In reply.

PMID- 23540048
TI  - Outbreak news. Poliovirus isolation, Egypt.

PMID- 23540049
TI  - Meeting of the International Task Force for Disease Eradication - November 2012.

PMID- 23540050
TI  - Schistosomiasis: number of people treated in 2011.

PMID- 23540051
TI  - Framework for verifying elimination of measles and rubella.

PMID- 23540052
TI  - Monthly report on dracunculiasis cases, January-December 2012.

PMID- 23540053
TI  - Approach to hospital food is a recipe for disaster.

PMID- 23540054
TI  - NMC vows to 'keep a cool head' over Mid Staffs misconduct cases.

PMID- 23540056
TI  - Inspectors link up with patients' group to improve referral process.

PMID- 23540055
TI  - Regulator reviews guidance on delegating tasks to support staff.

PMID- 23540057
TI  - Atos strikes deals with NHS trusts to deliver disability assessments.

PMID- 23540058
TI  - For staff to speak out, cultural and legal obstacles must be overcome.

PMID- 23540059
TI  - Bring back memories.
AB  - Age Exchange is bringing reminiscence art to patients with dementia and it is
      raising their spirits as well as improving the working environment of nurses.

PMID- 23540060
TI  - Safe to delegate?
AB  - Some employers are delegating tasks to less qualified staff. This can present
      problems for nurses, who are accountable for work they pass on, and who may be
      asked to perform tasks without adequate training. This article sets out what to
      do in such circumstances.

PMID- 23540061
TI  - 'Anyone can be homeless'.
AB  - Being homeless often makes it difficult for people to access the health care they
      need. Award-winning nurse consultant in substance abuse Louise Poley is bringing
      services to homeless clients instead of expecting them to fit into a system
      designed for people with conventional lifestyles.

PMID- 23540062
TI  - Connecting for health.
AB  - The College of Medicine is a unique alliance of nurses, healthcare professionals,
      scientists and patients to promote partnerships in health care and re-focus the
      NHS's efforts on prevention. It seeks to break down hierarchical divides between
      the professions and give patients a voice to say what matters to them. The RCN's
      general secretary is urging nurses to become involved.

PMID- 23540063
TI  - Improving the rates of organ donation for transplantation.
AB  - Organ donation is a complex and sensitive area. It is complicated by ethical,
      legal and social factors, as well as differing views about consent. Although
      organ donation rates have risen, there continues to be a significant gap between
      organ supply and demand. Despite previous calls for a change to the opt-in
      consent system used in England, and the move towards presumed or opt-out consent
      in Wales, the Organ Donation Taskforce rejected any such policy change in
      England, in favour of improving the infrastructure and systems surrounding organ
      donation. This article examines the various systems of consent for organ donation
      and strategies for improving organ donation rates.

PMID- 23540064
TI  - Factors influencing attrition rates in midwifery students.
AB  - Student attrition in higher education institutions has long been an area of
      concern. Voluntary withdrawal of nursing and midwifery students from courses is
      an increasing trend. A review of student records was conducted to examine the
      reasons for withdrawal from pre-registration midwifery programmes at University
      Campus Suffolk. Wrong career choice was identified by the majority of students
      who withdrew voluntarily. These findings were used in conjunction with
      theoretical frameworks to establish ways of improving selection and recruitment
      strategies to reduce attrition on midwifery courses. These approaches should
      provide students with a sense of the institution's commitment to their
      integration and socialisation into the educational and clinical practice
      environment.

PMID- 23540065
TI  - Prevention and management of depression in primary care.
AB  - Depression is a common mental health condition in which severe and persistent
      symptoms can lead to suicidal ideation. Timely recognition of depression is
      essential to improve patients' mental health and quality of life. This article
      outlines strategies to manage depression in primary care. It is anticipated that
      after reading this article nurses will feel more confident in screening and
      treating patients with this debilitating condition.

PMID- 23540066
TI  - Trans fats.

PMID- 23540067
TI  - World of opportunity.

PMID- 23540068
TI  - 'We have time to talk and listen'.

PMID- 23540069
TI  - 'I came back from Africa better prepared for nursing'.

PMID- 23540070
TI  - The Keyes Award and Edward Lawrence Keyes, MD (1843-1924).

PMID- 23540071
TI  - Paronychia.

PMID- 23540072
TI  - What is Woringer-Kolopp disease?

PMID- 23540073
TI  - Bioequivalence in keratolytic activity of formulations vs its vehicle and
      comparator formulation: randomized, double-blind clinical trial.
AB  - This study assessed the bioequivalence, using keratolytic efficacy, of topical
      preparations studied in humans using adhesive tape stripping and biophysical
      methods. Ten healthy patients (3 men and 7 women [7 Caucasians and 3 Asians] mean
      age, 47 years) completed the study. Each coded product was randomly applied to
      the back according to the designated time of each sample. In addition, an
      untreated site (normal skin), and an untreated occluded site (chamber only)
      served as controls. At the end of the application time, each site was rinsed with
      tap water and then covered with a plastic chamber for 6 hours. Following removal
      of the chamber, the site was stripped for protein assay and squamometry analysis.
      This extends previous observations discerning bioequivalence resulting from
      different active materials with varying mechanism of action and potency on the
      skin. Results showed no significant difference between tested products. The novel
      formulations were of equal keratolytic activity to the "standard" (comparator)
      and hence bioequivalent in keratolytic activity.

PMID- 23540074
TI  - Perceptions and practices in submental fat treatment: a survey of physicians and
      patients.
AB  - Localized facial fat deposits are common, and treatment to restore and reshape
      the lower aspect of the face is mainly limited to surgical procedures. There has
      been a rapid growth in nonsurgical aesthetic procedures, and physicians and
      patients are seeking less invasive, nonsurgical facial rejuvenation options. Few
      data are published, however, on physician and patient perceptions and treatment
      of submental fat. This contribution reviews data from surveys of 78 physicians
      (dermatologists and plastic surgeons) and 385 patients who received nonsurgical
      facial rejuvenation. On average, physicians discussed fat reduction options with
      19% of their patients; 18% of these discussions involved fat under the chin. Most
      patients surveyed (80%) had submental fat, assessed by a clinician using a 5
      point rating scale. Submental fat was of concern to patients surveyed; 77%
      reported noticing extra fat under their chin and 61% wanted it reduced. Most
      patients (63%) surveyed would use an effective and well-tolerated noninvasive
      pharmacologic treatment for submental fat reduction. Patients were more likely to
      wish to reduce the fat below their chin if they had higher chin grade scores
      based on clinician assessment. Interesting insights are provided into the
      perceptions and behavior of physicians and patients with regard to submental fat
      reduction.

PMID- 23540075
TI  - Cutaneous viral diseases in HIV infection.

PMID- 23540076
TI  - Hair biology and its comprehensive sequence in female pattern baldness: diagnosis
      and treatment modalities--Part I.
AB  - Hair may be a source of concern for patients when there is a change in its
      texture, amount, or thickness. It can present in women as androgenic alopecia
      also called female pattern baldness, and in men as adrogenic alopecia, also
      called male pattern baldness. Thinning/rarefaction affecting the vertex is a
      progressive condition, and hair loss in women has been interpreted and classified
      differently from that in men. The Ludwig classification for women's hair loss
      seems to be the most accepted assessment, which will be outlined in this review,
      along with the hair growth cycle that encompasses anagen, catagen, telogen,
      exogen, and kenogen.

PMID- 23540077
TI  - Pseudo positive, pseudo positive negative, pseudo positive positive negative, and
      pseudo pseudo positive positive negative positive margins in dermatopathology.

PMID- 23540078
TI  - Borderline tuberculoid evolving across the leprosy spectrum.

PMID- 23540079
TI  - Hair extensions: novel "source" of a well-known contact allergen.

PMID- 23540080
TI  - Combining field therapies for actinic keratoses: novel approaches that intensify
      photodynamic therapy.
AB  - Actinic keratosis (AK) is a common dermatologic condition resulting from long
      term sun exposure. It is considered a precancerous lesion that may convert into a
      squamous cell carcinoma, which highlights the importance of prompt
      identification, early treatment and eradication of AK, and recurrence monitoring.
      Currently, there are many treatments available for widespread AKs that include a
      combination of local lesion destruction along with stimulation of an individual's
      immune response. Preliminary data from combination therapy studies demonstrate
      that these may offer improved efficacy, tolerability, and long-term results
      compared with monotherapy. The authors investigate combination systems aimed at
      intensifying photodynamic therapy for the treatment of AKs as reported at the 8th
      World Congress of the International Academy of Cosmetic Dermatology in Cancun,
      Mexico, and include a comprehensive literature review. Further investigations and
      data collection are in progress in order to solidify these promising results.

PMID- 23540081
TI  - New side effect of TNF-alpha inhibitors: morphea.
AB  - An otherwise healthy 45-year-old man with a 3-year history of poorly controlled
      psoriasis (no arthritis) was treated with etanercept 50-mg subcutaneous
      injections twice weekly for 3 months and then once weekly. Alternative treatment
      options were either unavailable (long commute for phototherapy) or
      contraindicated (history of alcohol abuse). The patient initially tolerated
      etanercept well with significant clinical improvement and had an uneventful
      course; however, approximately 18 months after initiating therapy, he abruptly
      developed dusky, indurated, and tender plaques on his abdomen and thighs at the
      sites of etanercept injections (Figure 1). There was also diffuse woody
      induration involving his flanks and back where injections had not been performed.
      His only recent prior exposure to an injectable medication was rabies vaccination
      in his arm 1 year earlier. The patient denied any systemic symptoms. Upon noting
      these findings, etanercept was immediately discontinued. Biopsy of an indurated
      plaque on his right lower abdomen revealed a superficial and deep perivascular
      lymphoplasmacytic inflammatory infiltrate in a background of thickened and
      hyalinized collagen fibers with notable loss of perieccrine fat (Figure 2). These
      features were most consistent with the inflammatory stage of morphea. Further
      work-up revealed a negative antinuclear antibody, anti-double-stranded DNA, anti
      Scl-70, and anti-centromere. Borrelia titers were not obtained. The differential
      diagnosis included scleredema and scleromyxedema; serum and urine protein
      electrophoresis were within normal limits. The sites were treated with
      intralesional corticosteroids. During the next 3 months, there was minimal
      progression of disease although the plaques of morphea had not yet resolved.

PMID- 23540082
TI  - What is the new knowledge gained through IJT in 2012?

PMID- 23540083
TI  - Tuberculous meningitis: do modern diagnostic tools offer better prognosis
      prediction?
AB  - BACKGROUND: The British Medical Research Council (BMRC) staging has been
      extensively used to evaluate the disease severity and establish the approximate
      prognosis of tuberculous meningitis. AIMS: This study aimed at analyzing the
      predictive accuracy for mortality and neurological sequelae of a set of clinical
      features, laboratory tests and imaging. METHODS: We compared the British Medical
      Research Council (BMRC) staging with a new scoring proposal to predict the
      prognosis of patients with Central Nervous System Tuberculosis. Data from Ecuador
      was collected. A score was built using a Spiegelhalter and Knill-Jones method and
      compared with BMRC staging with a ROC curve. RESULTS: A total of 213/310 patients
      (68.7%) were in BMRC stage II or III. Fifty-seven patients died (18.3%) and 101
      (32.5%) survived with sequelae. The associated predictors were consciousness
      impairment (p = 0.010), motor deficit (p = 0.003), cisternal effacement (p =
      0.006) and infarcts (p = 0.015). The new score based on these predictors yielded
      a larger area under the curve of 0.76 (95% CI: 0.70-0.82), but not significantly
      different from the BMRC (0.72: 95% CI: 0.65-0.77). CONCLUSIONS: This modern score
      is easy to apply and could be a sound predictor of poor prognosis. However, the
      availability of modern tests did not improve the ability to predict a bad
      outcome.

PMID- 23540084
TI  - Genito-urinary tuberculosis revisited--13 years' experience of a single centre.
AB  - BACKGROUND: Tuberculosis had been declared by the World Health Organization (WHO)
      as 'public health emergency' in 1993. Extra pulmonary tuberculosis (E.P.T.B.)
      comprises 20-25% total burden of the disease in which genitourinary tuberculosis
      (GU.T.B.) is 4%. Timely diagnosis and treatment will prevent the sequelae of this
      disease. AIMS: To know the varied clinical presentations, diagnostic modalities
      and management of G.U.T.B. METHODS: During a 13-year-period, 117 retrospective
      cases of GUTB were admitted in the tertiary care centre. They were analyzed for
      clinical presentation, diagnostic modalities and management. RESULTS: Young
      patients mainly in third decade of life were commonly affected with higher
      incidence in females. In our study, the most common presentation was irritative
      voiding symptoms (66.47%) followed by haematuria (47.60%). Although it can affect
      the entire organ in genito-urinary system but, in the present study, kidney was
      the most affected organ (64.9%) following ureter (27.35%), urinary bladder
      (17.09%), prostate (3.4%) and epididymis (5.19%). In this study, we had not
      encountered any case of testicular and penile tuberculosis. Among the different
      diagnostic modalities in this study, the diagnostic positivity rate was 41.6% for
      the urine AFB test, 55.4% for the urine M. tuberculosis culture test and 67.7%
      for PCR. Chest x-ray was positive in 25.6% (30). ESR was raised in 62.5% and
      Mantoux test was positive in 61.2% patients. CONCLUSION: A high index of
      suspicion and a wide range of investigations may be required to achieve a
      complete diagnosis of genitourinary tuberculosis. Though short course
      chemotherapy with four-drug-regimen for six-month-duration is the mainstay of
      treatment, surgical interventions were required in 60% of cases of this study.

PMID- 23540085
TI  - TB/ HIV coordination through Public Private Partnership: lessons from the field.
AB  - BACKGROUND: Co-infection with tuberculosis adversely affects the quality of life
      of HIV infected individuals and additionally, HIV testing among TB patients gives
      an opportunity for prevention and treatment of HIV infection. TB-HIV coordination
      activities are therefore a good public health intervention. METHODS: It was a
      three-year Public Private Partnership Project, implemented in four districts of
      Maharashtra, to improve access to public health facilities through community
      awareness and motivating referrals. Outreach workers were engaged to motivate
      patients attending Integrated Counselling and Testing Centres (ICTCs) and
      Designated Microscopy Centres (DMCs) for cross referrals and adherence to
      services. Community leaders and private health providers were sensitized to
      issues around TB and HIV/AIDS. OBSERVATIONS: 357 outreach workers referred 17,200
      individuals for HIV testing and 32,549 TB suspects were referred for testing. An
      average of 18% TB cases (13% to 26%) and 7% (4% to 13%) HIV infected cases were
      identified. Involvement of PLHA and cured TB patients can better motivate
      symptomatics to avail of diagnostic services. Erratic funding affects smooth
      implementation of programmes. CONCLUSION: Public Private Partnerships improve
      access to care. Constant dialogue between all stake holders is essential for
      successful implementation of such partnerships.

PMID- 23540087
TI  - Delay in diagnosis and treatment among TB patients registered under RNTCP Mandi,
      Himachal Pradesh, India, 2010.
AB  - BACKGROUND: Delay in TB diagnosis and treatment is associated with increased
      transmission, morbidity and mortality. Patient and provider factors are
      responsible for such delays. We conducted a study to estimate these delays and
      identify associated factors among new sputum positive (NSP) TB patients in Mandi
      district, Himachal Pradesh. METHODS: We interviewed 234 NSP patients to collect
      information on their health seeking behaviour. We conducted univariate and
      multivariate analysis to identify factors associated with longer delays. RESULTS:
      Median patient, health system and total delay were 15, 13 and 36 days
      respectively. Significant factors associated with total delay included patients'
      knowledge about TB, seeking care from non-specialized individuals as the first
      action, consulting > 2 health facilities before diagnosis and consulting private
      health facilities. Patients with low family income and those who had high
      expenditure on consultations before initial diagnosis were associated with
      patient and health system delay respectively. CONCLUSION: It is necessary to
      increase community awareness about TB symptoms and availability of free treatment
      at public health facilities. Educating private physicians about the need for
      maintaining a high index of suspicion of tuberculosis and sensitizing drug-store
      owners to refer the chest symptomatics to government health facilities would also
      help in reducing these delays.

PMID- 23540086
TI  - An overview and mapping of childhood tuberculosis: prevalence, scientific
      production and citation analysis.
AB  - AIM: The study aimed to analyze publications in the field of "pediatric
      tuberculosis" and associate them with regional Tuberculosis (TB) profile.
      METHODS: A schematic analysis of scientific production in the field of pediatric
      tuberculosis between 1990 and 2010 using ISI web of science was carried out.
      Terms used for searches were each as a combination of "Mycobacterium
      Tuberculosis", or "Tuberculos*" and "Child", or "Infant", or "New born", or
      "Neonatal", or "Adolescent", or "Pediatric". Features including year of
      publication, citation per year, country of origin, funding state, contributing
      university, language, leading journals and authors, and highly cited articles,
      main journal publishing these articles were taken into account. RESULTS: The
      search retrieved 3417 articles (of 4559 total) with an almost gradual annually
      progressive pattern from 20 (in 1990) to 302 (in 2009) which have been cited
      totally 48459 times and 14.18 times per article. The greatest contribution
      originated from United States of America (25.11%) followed by South Africa
      (12.17%), and England (11.18%). Interestingly, 82.4% of all South African
      articles were from Stellenbosch University and Cape Town University on contrary.
      CONCLUSIONS: International Journal of Tuberculosis and Lung Disease ranked as the
      first with regard to the number of articles and Lancet with regard to the number
      of highly cited articles. Developing countries excluding South Africa despite
      their high prevalence scarcely contribute to the field and USA is the leading
      country in the field.

PMID- 23540088
TI  - Cervical tuberculosis masquerading as cancer cervix: a report of three cases.
AB  - Tuberculosis is still frequently observed in third world countries like Africa
      and Asia. Here we report three cases of genital tuberculosis with variable
      presentations. First case was a lady of reproductive age group who presented with
      polymenorrhea and post-coital bleeding with unhealthy cervix. Histopathology of
      cervical tissue revealed tubercular cervicitis. Second and third cases presented
      with different complaints like discharge per vaginum, post-coital bleeding and
      pain in lower abdomen with growth over the cervix. Cervical biopsy was
      inconclusive of tuberculosis but endometrial tissue sampling for TB PCR was
      positive. This shows that newer diagnostic marker test can help us to detect
      secondary genital tuberculosis.

PMID- 23540089
TI  - Tuberculosis of odontogenic cyst.
AB  - Tuberculous infection of the oral tissues is a rare finding. An interesting case
      of primary tuberculosis of mouth is described, presenting as persistent discharge
      of pus from the lower wisdom tooth region. Incisional biopsy revealed features of
      an infected dentigerous cyst while histopathological examination of the excised
      lesion showed keratinizing cyst with secondary infection. Non-healing of the bony
      defect prompted curettage of the area and the submitted sample microscopically
      showed granuloma with characteristic Langhans' giant cells, raising the suspicion
      of underlying systemic tuberculosis. The importance to the dental surgeon in the
      recognition, especially by use of pathological examination, is emphasized and
      also the value of diagnosis for the patients and the community.

PMID- 23540090
TI  - Co-existence of HIV, active tuberculosis and aspergilloma in a single individual-
      a case report.
AB  - Tuberculosis (TB) is a disease as old as mankind, whereas in India the first case
      of Human Immunodeficiency Virus (HIV) was reported in 1986. HIV and TB are so
      closely connected that their relationship is often described as a co-epidemic.
      Aspergilloma (Fungal Ball, Mycetoma) represents a saprophytic growth of
      aspergillus that colonizes in the preformed cavities commonly due to pulmonary
      tuberculosis (PTB). We report a case of HIV, active pulmonary tuberculosis and
      aspergilloma occurring in the same patient. Despite our best efforts, we could
      not lay our hands on any similar case in the medical literature.

PMID- 23540091
TI  - HIV positivity in TB suspects--an observational, non-randomized study.
AB  - AIMS: The present study was carried out to determine the prevalence of TB, HIV,
      and TB- HIV co-infection in 618 patients who attended the health institute for TB
      diagnosis and treatment at a rural tertiary care hospital in Punjab. METHODS:
      Pulmonary T.B was diagnosed by sputum smear microscopy, culture and extra
      pulmonary TB was diagnosed by X-ray, CT and other methods. HIV diagnosis was made
      by testing the sera by 3E/R/S (ELISA/RAPID/SIMPLE) tests as per NACO guidelines.
      RESULTS: Of the total 618 patients, 74(12%) were patients of pulmonary TB, out of
      whom 72 were diagnosed by Ziehl Neelsen (ZN) staining and two were diagnosed by
      culture as the ZN stained smear was negative, 169(27.3%) were cases of extra
      pulmonary TB. Three out of 618 were HIV positive. 1.23% were TB- HIV co-infected.
      CONCLUSION: The risk of developing TB increases in patients with HIV. So, HIV and
      TB programmes should be collaborated together and should be closely integrated
      with medical care to curb the spread of these deadly diseases.

PMID- 23540092
TI  - Your voice in the legislature.

PMID- 23540093
TI  - Entering the golden age of primary care.

PMID- 23540094
TI  - Certifying death. A physician's guide to navigating your legal responsibility.

PMID- 23540095
TI  - Meaningful use: the next step.

PMID- 23540096
TI  - Vulvodynia in Arkansas: a survey of Arkansas gynecologists' practice experience
      and management of vulvar pain.
AB  - The objective of this survey was to determine the level of experience OB/GYN
      (Obstetrics & Gynecology) physicians in the state of Arkansas have in seeing and
      managing patients with vulvar pain, commonly known as vulvodynia. The 8 question,
      anonymous survey was mailed to Arkansas OB/GYN physicians. The survey assessed
      the experience of the providers, the age range of their patients, and whether or
      not they treat and/or refer. Thirty of 182 surveys were returned for a rate of
      16.4%. The survey revealed that physicians are moderately comfortable treating
      vulvodynia within their practice and refer mostly for treatment failure.

PMID- 23540097
TI  - Mandating nutrient menu labeling in restaurants: potential public health
      benefits.
AB  - RATIONALE: Many Americans have replaced home-cooked meals with fast food and
      restaurants meals. This contributes to increased incidences of overweight and
      obesity. Implementing policies that require restaurants to disclose nutrition
      information has the potential to improve nutrition knowledge and food behaviors.
      The purpose of this paper was to examine the potential health benefits of
      nutrient menu labeling in restaurants, the progress of this legislation and to
      provide results regarding the implementation of these policies. METHOD: Data
      sources were obtained from a search of multiple databases including PubMed,
      Science Direct, Academic Search Premier, and Google Scholar. Study inclusion
      criteria were publication in the past ten years, obesity prevention, and
      utilization of nutrition labeling on menus in restaurants. RESULTS: The initial
      policies to provide consumers with nutrition information in restaurant settings
      began at the state levels in 2006. These laws demonstrated success, other states
      followed, and a national law was passed and is being implemented. DISCUSSION:
      Mandating nutrient menu disclosure has the potential to influence a large number
      of people; this legislation has the opportunity to impact Americans who dine at a
      fast food or chain restaurant. Given the growing obesity epidemic, continued
      research is necessary to gauge the effectiveness of this new law and its effects
      on the health status of the American people.

PMID- 23540098
TI  - Children presenting with fractures in an emergency room: child abuse?

PMID- 23540099
TI  - The aftermath of December 14, 2012.

PMID- 23540100
TI  - The school wellness nurse: a model for bridging gaps in school wellness programs.
AB  - Incidence of pediatric overweight continues to pose significant national health
      threats due to associated co-morbid, chronic conditions, including diabetes
      mellitus, hypertension, dyslipidemia, and others. Interventions to address health
      behaviors of children often focus on the school environment because of the
      opportunity to have an impact on child health through nutrition education and
      optimization of the school food and physical activity environments. Federally
      mandated school wellness policies provide schools with clear objectives to
      address poor health behaviors of their students. Unfortunately, these policies
      are largely ineffective because of identified gaps in their administration.
      Competing school and community factors further fragment their implementation. To
      bridge the gaps between wellness policy development and implementation, a school
      wellness nurse model is proposed. The role of the school wellness nurse serves to
      weave health interventions into the fabric of the school and community
      environments--displacing behaviors and policies inconsistent with national health
      goals to reduce incidence of overweight.

PMID- 23540101
TI  - Adolescents and headaches: maintaining control.
AB  - Migraine headaches, much like a chronic illness, are reported to negatively
      affect adolescents physically, mentally, and socially, further disturbing this
      already turbulent time of development. Prior migraine research is limited in
      adolescents, and no qualitative studies have examined the lived experience of
      adolescents with migraines. This interpretive phenomenological study explored the
      experience of living with migraines in six adolescents ranging in age from 12 to
      17 years. After coding data and grouping into clusters, three themes emerged: 1)
      maintaining control by either pressing on and enduring the burden, or by
      disengaging and isolating self; 2) mind overload; and 3) unsettling
      manifestations. Adolescents approach migraine episodes by either continuing with
      their life as "normal," or by removing themselves physically and/or emotionally.
      By understanding the potentially unique physical and psychological disruptions
      that adolescents with migraines experience, nurses can offer education, provide
      nonpharmacologic interventions, and conduct further research that will improve
      health outcomes.

PMID- 23540102
TI  - Interpretive phenomenology.

PMID- 23540103
TI  - A nursing brief: emerging best practice in Department of Children and Families
      nursing.
AB  - In 2012, more than 400,000 children in the United States were in the child
      welfare system because of abuse or neglect. These children are uniquely
      vulnerable and present multiple health challenges to child welfare and health
      professionals. According to the most recent Child and Family Services Reviews
      (CFSR) from the U.S. Department of Health and Human Services Administration for
      Children and Families' Children's Bureau (2010), none of the 50 states, Puerto
      Rico, and the District of Columbia were "in substantial conformity" in meeting
      the well-being outcome for the physical and mental health needs of the children
      in their care. To address this deficiency, Connecticut nurses caring for children
      involved with Department of Children and Families (DCF) collaborated to establish
      nursing standards of practice leading to improved health services for children in
      care and a mechanism to readily transfer health information. Post-implementation
      evaluation revealed improved quality of care and the availability of enhanced
      health information. These endeavors have led to the recognition that nurses
      working in DCF venues are members of an emerging professional nursing specialty:
      "nursing in child welfare."

PMID- 23540104
TI  - What's that smell? A 10-year-old female with a strong odor.

PMID- 23540105
TI  - Expanded back to sleep guidelines.

PMID- 23540106
TI  - Cline and Greene's Parenting children with health issues: essential guidance.

PMID- 23540107
TI  - What is the risk for exposure to vector-borne pathogens in United States national
      parks?
AB  - United States national parks attract > 275 million visitors annually and
      collectively present risk of exposure for staff and visitors to a wide range of
      arthropod vector species (most notably fleas, mosquitoes, and ticks) and their
      associated bacterial, protozoan, or viral pathogens. We assessed the current
      state of knowledge for risk of exposure to vector-borne pathogens in national
      parks through a review of relevant literature, including internal National Park
      Service documents and organismal databases. We conclude that, because of lack of
      systematic surveillance for vector-borne pathogens in national parks, the risk of
      pathogen exposure for staff and visitors is unclear. Existing data for vectors
      within national parks were not based on systematic collections and rarely include
      evaluation for pathogen infection. Extrapolation of human-based surveillance data
      from neighboring communities likely provides inaccurate estimates for national
      parks because landscape differences impact transmission of vector-borne pathogens
      and human-vector contact rates likely differ inside versus outside the parks
      because of differences in activities or behaviors. Vector-based pathogen
      surveillance holds promise to define when and where within national parks the
      risk of exposure to infected vectors is elevated. A pilot effort, including 5-10
      strategic national parks, would greatly improve our understanding of the scope
      and magnitude of vector-borne pathogen transmission in these high-use public
      settings. Such efforts also will support messaging to promote personal protection
      measures and inform park visitors and staff of their responsibility for personal
      protection, which the National Park Service preservation mission dictates as the
      core strategy to reduce exposure to vector-borne pathogens in national parks.

PMID- 23540108
TI  - Contribution to the knowledge of the Hippoboscidae (Diptera) from the Republic of
      Korea.
AB  - Eight species of Hippoboscidae from 13 bird hosts are reported from the Republic
      of Korea (ROK). A new species of the genus Crataerina von Olfers with reduced
      wings is described, and it was collected from a Pacific Swift (Apus pacificus
      Latham; Apodiformes, Apodidae). Icostafenestella Maa is recorded for the first
      time from the ROK. Ornithoica tridens Maa is synonymized with O. momiyamai
      Kishida. Turdus chrysolaus Temminck and Zoothera (=Turdus) sibirica (Pallas) are
      recorded as new birds host for I. fenestella and O. unicolor Speiser,
      respectively. Morphological identification keys are also presented for the
      species of the genus Crataerina in the Palaearctic region, and for the species of
      the Hippoboscidae in the ROK.

PMID- 23540109
TI  - Changes in species richness and spatial distribution of mosquitoes (Diptera:
      Culicidae) inferred from museum specimen records and a recent inventory: a case
      study from Belgium suggests recent expanded distribution of arbovirus and malaria
      vectors.
AB  - Mosquito (Diptera: Culicidae) distribution data from a recent inventory of native
      and invading mosquito species in Belgium were compared with historical data from
      the period 1900-1960 that were retrieved from a revision of the Belgian Culicidae
      collection at the Royal Belgian Institute of Natural Sciences. Both data sets
      were used to investigate trends in mosquito species richness in several regions
      in Belgium. The relative change in distribution area of mosquito species was
      particularly important for species that use waste waters and used tires as larval
      habitats and species that recently shifted their larval habitat to artificial
      larval habitats. More importantly, several of these species are known as vectors
      of arboviruses and Plasmodium sp. and the apparent habitat shift of some of them
      brought these species in proximity to humans. Similar studies comparing current
      mosquito richness with former distribution data retrieved from voucher specimens
      from collections is therefore encouraged because they can generate important
      information concerning health risk assessment at both regional and national
      scale.

PMID- 23540110
TI  - Lone star tick (Acari: Ixodidae) occurrence in Nebraska: historical and current
      perspectives.
AB  - In 2010 and 2011, field collections were undertaken to determine the geographic
      range of the lone star tick, Amblyomma americanum (L.), in Nebraska In addition,
      tick identifications from submissions by the general public dating to 1911 were
      examined. Consistent lone star tick identifications from extreme southeast
      Nebraska began in 1987. Specimens have been identified from 27 counties, making
      lone star ticks the second most frequently and second most widely reported tick
      in the state after Dermacentor variabilis (Say). Surveys conducted in 70 sites in
      43 counties yielded 2,169 ticks of which 1,035 were lone star ticks. Lone star
      ticks were more frequent in the southeast portion of the state and ticks were
      found in nine counties from which there were no known submissions. Life stage
      peaks observed during the surveys corresponded with those observed from
      submissions. Other ticks, incidental to the study, were also collected. Woody
      plant expansion into the tallgrass prairie, white-tailed deer (Odocoileus
      virgianianus L.) and wild turkey (Meleagris gallopavo L.) population growth, and
      the increased frequency of milder winters may be facilitating lone star tick
      occurrence in the region. Further studies will assess lone star tick
      establishment and disease pathogen prevalence in the state.

PMID- 23540111
TI  - Laboratory development and field validation of Phormia regina (Diptera:
      Calliphoridae).
AB  - Immature blow flies (Diptera: Calliphoridae) collected from decomposing human
      remains are often used to determine the minimum postmortem interval (PMImin).
      Phormia regina (Meigen) is a common blow fly of cosmopolitan distribution that is
      often associated in such cases. P. regina development at two different cyclic
      temperatures was examined in this study. A field validation study was conducted
      to determine the accuracy of applying these data to determine the PMImin. Minimal
      total development time was 32.52 d at cyclic 14.0 +/- 2.0 degrees C and 16.60 d
      at cyclic 20.5 +/- 3.1 degrees C. The minimal larval development was
      significantly different (P < 0.05) across temperatures. Larval development needed
      15.5 d at 14.0 degrees C and 7.5 d at 20.5 degrees C. For the validation study,
      instar, mean, and maximum of length and weight data of the larvae collected in
      the field were analyzed with data generated from the 20.5 degrees C treatment, as
      it more closely reflected the field conditions experienced. Accuracy in
      estimating PMImin, was highly variable depending on the unit of measurement used
      and instar of P. regina collected from the field. Using the oldest instar to
      estimate a PMImin resulted in ranges that always encompassed the true time of
      colonization. Accuracy in hours when using measurements units as mean length or
      weight, and maximal length or weight, varied among the larval instars. In the
      first instar the greatest overestimation was made with maximal weight while the
      greatest underestimation was made with mean weight. The most accurate estimate
      produced with first instars was based on maximal length. In the second instar,
      there was no overestimation and the greatest underestimation was made with mean
      weight and the most accurate estimate produced was with maximal length. In the
      third instar, the greatest overestimation was made with maximal length, and the
      greatest underestimation was made with mean weight. The estimated time of
      colonization based on maximal weight was most accurate for third instars.

PMID- 23540112
TI  - A dengue vector surveillance by human population-stratified ovitrap survey for
      Aedes (Diptera: Culicidae) adult and egg collections in high dengue-risk areas of
      Taiwan.
AB  - Aedes aegypti L. is the primary dengue vector in southern Taiwan. This article is
      the first report on a large-scale surveillance program to study the spatial
      temporal distribution of the local Ae. aegytpi population using ovitraps
      stratified according to the human population in high dengue-risk areas. The
      sampling program was conducted for 1 yr and was based on weekly collections of
      eggs and adults in Kaohsiung City. In total, 10,380 ovitraps were placed in 5,190
      households. Paired ovitraps, one indoors and one outdoors were used per 400
      people. Three treatments in these ovitraps (paddle-shaped wooden sticks, sticky
      plastic, or both) were assigned by stratified random sampling to two areas (i.e.,
      metropolitan or rural, respectively). We found that the sticky plastic alone had
      a higher sensitivity for detecting the occurrence of indigenous dengue cases than
      other treatments with time lags of up to 14 wk. The wooden paddle alone detected
      the oviposition of Ae. aegypti throughout the year in this study area.
      Furthermore, significantly more Ae. aegypti females were collected indoors than
      outdoors. Therefore, our survey identified the whole year oviposition activity,
      spatial-temporal distribution of the local Ae. aegypti population and a 14 wk lag
      correlation with dengue incidence to plan an effectively proactive control.

PMID- 23540113
TI  - The effects of Solenopsis invicta (Hymenoptera: Formicidae) and burned habitat on
      the survival of Amblyomma americanum (Acari: Ixodidae) and Amblyomma maculatum
      (Acari: Ixodidae).
AB  - Identifying ways in which humans can reduce tick populations is important for
      preventing the spread and emergence of diseases. During a recent study on effects
      of long-term prescribed burning on ticks, differences in species composition were
      observed with lone star ticks, Amblyomma americanum (L.), preferring unburned
      habitats and Gulf Coast ticks, Amblyomma maculatum (Koch), preferring burned
      habitats. Interestingly, the red imported fire ant, Solenopsis invicta Buren, is
      found predominantly in disturbed habitats, such as burned habitats, and studies
      have reported that red imported fire ants prey on lone star ticks. To better
      understand drivers of tick population differences in burned habitats, the current
      study was conducted to evaluate the effects of red imported fire ant and habitat
      on survival of lone star and Gulf Coast ticks. Within treatments (burned habitat
      with red imported fire ants, burned habitat without red imported fire ants, and
      unburned habitat without red imported fire ants), 10 tick enclosures were
      installed and seeded with engorged lone star or Gulf Coast tick nymphs. After
      molting, ticks within enclosures were collected. Survival of lone star ticks in
      burned habitats (regardless of red imported fire ant presence) was significantly
      lower compared with unburned habitat. Gulf Coast ticks had significantly greater
      survival in burned habitats (regardless of red imported fire ant presence)
      compared with lone star ticks. In this study, burning status was more important
      for survival of ticks than presence of red imported fire ants, with Gulf Coast
      ticks surviving better in burned habitat that typically experiences higher
      temperatures and lower humidity.

PMID- 23540114
TI  - Behavioral aspects of Lutzomyia longipalpis (Diptera: Psychodidae) in urban area
      endemic for visceral leishmaniasis.
AB  - The study of some of the behavioral aspects of the main vector of Leishmania
      infantum chagasi Cunha & Chagas in the Americas, Lutzomyia longipalpis (Lutz &
      Neiva), such as dispersion, population size, and vector survival rates, is
      important for the elucidation of the mechanisms of visceral leishmaniasis
      transmission. These parameters were studied by means of capture-mark-release
      recapture experiments in an urban area of Campo Grande municipality, an endemic
      area of visceral leishmaniasis, situated in Mato Grosso do Sul state, Brazil. Six
      capture-mark-release-recapture experiments were undertaken between November 2009
      and November 2010 and once in January 2012 with a view to assessing the
      population size and survival rate of Lu. longipalpis. The insects were released
      in a peridomicile surrounded by 13 residences. The recaptures were undertaken
      with automatic light traps for four consecutive weeks after release in the
      surrounding area. In total, 3,354 sand flies were captured, marked, and released.
      The overall recapture rate during the capture-mark-release-recapture experiments
      was 4.23%, of which 92.45% were recaptured at the release site, indicating
      limited dispersal. The greatest distance recorded from the release site was 165 m
      for males and 241 m for females. The male daily survival rate, calculated on the
      basis of regressions from the numbers of marked recaptured insects during the 15
      successive days after release was 0.897. The estimated male population size
      measured by the Lincoln Index was 10,947.127. Though Lu. longipalpis presented a
      limited dispersion the physical barriers typical of urban environments did not
      prevent the sand flies from flying long distances.

PMID- 23540115
TI  - Effects of age and size on Anopheles gambiae s.s. male mosquito mating success.
AB  - Before the release of genetically-modified or sterile male mosquitoes in an
      attempt to control local populations of malaria vectors, it is crucial to
      determine male traits involved in mating success. The effects of male size and
      age as determinants of male mating success in Anopheles gambiae s.s. were
      measured in the field and under laboratory conditions in Burkina Faso. First, the
      body sizes (estimated by wing length) of mating, swarming, and indoor-resting
      male mosquitoes were compared over a 3-yr period (2006-2009) from July to October
      in Soumousso and Vallee du Kou, two villages in western Burkina Faso. Second, the
      age structure of swarming and resting male mosquitoes were characterized based on
      the number of spermatocysts and the proportion of sperm in the reservoir of wild
      caught male testis. Third, male age effects on the insemination rate of female
      An. gambiae were investigated in the laboratory. The mean size of males collected
      in copula was significantly larger than the mean for swarming males and indoor
      resting males. The optimum male age for successful insemination of females was 4
      8 d. These results suggest that male size is an important trait in determining
      male mating competitiveness in the field. Although age was not found to be a
      significant factor in mating competitiveness, it was significantly correlated
      with swarming behaviors in the field and insemination success in the laboratory.
      The implications of these results in terms of sexual selection in An. gambiae and
      vector control programs are further discussed.

PMID- 23540116
TI  - Phylogeography and spatio-temporal genetic variation of Aedes aegypti (Diptera:
      Culicidae) populations in the Florida Keys.
AB  - Aedes aegypti (L.) is the principal mosquito vector of dengue fever, the second
      most deadly vector-borne disease in the world. In Ae. aegypti and other arthropod
      disease vectors, genetic markers can be used to inform us about processes
      relevant to disease spread, such as movement of the vectors across space and the
      temporal stability of vector populations. In late 2009, 27 locally acquired cases
      of dengue fever were reported in Key West, FL. The last dengue outbreak in the
      region occurred in 1934. In this study, we used 12 microsatellite loci to examine
      the genetic structure of 10 Ae. aegypti populations from throughout the Florida
      Keys and Miami to assess gene flow along the region's main roadway, the Overseas
      Highway. We also assessed temporal genetic stability of populations in Key West
      to determine whether the recent outbreak could have been the result of a new
      introduction of mosquitoes. Though a small amount of geographic genetic structure
      was detected, our results showed high overall genetic similarity among Ae.
      aegypti populations sampled in southeastern Florida. No temporal genetic signal
      was detected in Key West populations collected before and after the outbreak.
      Consequently, there is potential for dengue transmission across southeastern
      Florida; renewed mosquito control and surveillance measures should be taken.

PMID- 23540117
TI  - Ecological and genetic analyses of the complete genomes of Culex flavivirus
      strains isolated from Culex tritaeniorhynchus and Culex pipiens (Diptera:
      Culicidae) group mosquitoes.
AB  - Culex flavivirus (CxFV) is an insect-specific flavivirus that was first reported
      in 2007 in Japan. CxFV strains were isolated from Culex tritaeniorhynchus Giles
      and Culex pipiens L. group mosquitoes and genetically characterized in Toyama
      Prefecture, Japan, from 2004 to 2009, to reveal host specificity, mode of
      transmission, and seasonal and geographical distribution. The minimum infection
      rate (MIR) of CxFV within Cx. tritaeniorhynchus populations was 0.3 and much
      lower than that within Cx. pipiens group (17.9). The complete genome sequences of
      11 CxFV isolates (four from Cx. tritaeniorhynchus and seven from Cx. pipiens
      group) consisted of 10,835-10,837 nucleotides. When these 11 isolates and five
      reference strains (NIID-21-2 and Tokyo strains from Japan, Iowa07 and HOU24518
      strains from the United States, H0901 strain from China) were compared, there
      were 95.2-99.2% nucleotide and 98.1-99.8% amino acid identities. Phylogenetic
      analysis showed that the 11 isolates were divided into four clusters. One cluster
      consisted of five isolates from Cx. pipiens group and Cx. tritaeniorhynchus from
      one site and their nucleotide sequences almost completely matched. One cluster
      consisted of an isolate with a unique sequence from a Cx. pipiens group mosquito
      captured in an aircraft from Taiwan, suggesting that it was introduced from
      abroad. CxFV strains were divided into several groups according to countries when
      nucleotide sequences of CxFV available in GenBank and 11 Toyama isolates were
      compared. These results suggest that CxFV is maintained in nature among Culex
      mosquitoes in a mosquito habitat-specific but not a species-specific manner.

PMID- 23540118
TI  - Larvicidal and cytotoxic activities of extracts from 11 native plants from
      northeastern Mexico.
AB  - Of all mosquito-borne viral diseases, dengue is spreading most rapidly worldwide.
      Conventional chemical insecticides (e.g., organophosphates and carbamates)
      effectively kill mosquitoes at their larval stage, but are toxic to humans.
      Natural product-based insecticides may be highly specific. Herein, we report the
      insecticidal activities of 11 native Mexican plants against Aedes aegypti (L).
      Ether extracts of Ambrosia confertiflora De Candolle, Thymus vulgaris (L.), and
      Zanthoxylum fagara (L.), and both ether and methanol extracts of Ruta chalepensis
      L. were significantly larvicidal toward the dengue mosquito after 24 h of
      exposure. Of them, only the ether extract of A. confertiflora was toxic to Vero
      cells. In conclusion, the ether extracts of Thymus vulgaris, Z. fagara, and both
      ether and methanol extracts of Ruta chalepensis L., could be considered as
      potential bioinsecticides.

PMID- 23540119
TI  - Anopheles arabiensis sperm production after genetic manipulation, dieldrin
      treatment, and irradiation.
AB  - The use of the sterile insect technique relies on the release of sterilized mass
      reared male insects which, before field releases, endure several unnatural
      treatments. In the case of Anopheles arabiensis (Patton) sterile insect technique
      program in Sudan, the genetic background of the original strain was first changed
      to create a genetic sexing strain that is based on a dieldrin-resistant mutation.
      Secondly, the eggs of the genetic sexing strain require treatment with dieldrin
      to allow complete elimination of female L1 larvae to enable the release of males
      only. Finally, male mosquitoes receive an irradiation dose of 70 Gy as pupae for
      sterilization. The effects of these treatments on sperm production were tested
      separately and in combination. Irradiation alone significantly decreased the
      initial sperm number and prevented new sperm production. However, the dieldrin
      treatment, aimed at eliminating females, appears to have an unexpected
      radioprotectant effect.

PMID- 23540120
TI  - Pilot field trials with Aedes albopictus irradiated sterile males in Italian
      urban areas.
AB  - The pilot field studies here presented are part of a long-term research program
      aimed to develop a cost-effective sterile insect technique (SIT) methodology to
      suppress Aedes albopictus (Skuse) populations. Aedes albopictus is a mosquito
      species mainly developing in man-made containers and with an island-like urban
      and suburban distribution. These two features make the application of the sterile
      insect technique a possible control strategy. Five trials have been performed in
      three small towns from 2005 to 2009 (Emilia-Romagna region, northern Italy).
      Reared male pupae, sexed by a sieving technique allowing the recovery of
      approximately 26-29% of males, were exposed to gamma rays and immediately
      released in the field. Adult population density was estimated based on a weekly
      monitoring of egg density in the ovitraps, whereas induced sterility was
      estimated by measuring the hatching percentage of weekly collected eggs in SIT
      and control areas. Results showed that sterile males released at the rate of 896
      1,590 males/ha/wk induced a significant sterility level in the local population.
      In addition, when the sterility level achieved values in the range of 70-80%, a
      similar reduction also was found for the egg density in the ovitraps. We could
      estimate that the minimum egg sterility value of 81% should be maintained to
      obtain suppression of the local population. Immigration of mated females was not
      a main issue in the small villages where trials have been run.

PMID- 23540121
TI  - Determination of acaricide resistance in Rhipicephalus (Boophilus) microplus
      (Acari: Ixodidae) field populations of Argentina, South Africa, and Australia
      with the Larval Tarsal Test.
AB  - Infestations with ticks have an important economic impact on the cattle industry
      worldwide and resistance to acaricides has become a widespread phenomenon. To
      optimize their treatment strategy, farmers need to know if and against which
      classes potential acaricide-resistance does occur. Bioassays are used to assess
      the resistance level and pattern of Rhipicephalus (Boophilus) microplus
      populations. The objective of the current study was to assess the susceptibility
      of field populations originating from Argentina (8), South Africa (3), and
      Australia (2) using the Larval Tarsal Test. Nine acaricidal compounds from five
      major classes were tested: organosphosphates, synthetic pyrethroids (SP),
      macrocyclic lactones, phenylpyrazols, and amidines. The resistance ratios at
      concentrations inducing 50 and 90% mortality were used to detect established and
      emerging resistance. This study confirmed the newly reported presence of amitraz
      resistance in populations from Argentina In addition, resistance to SP appeared
      to be widespread (88%) in the Argentinean farms, which had been selected based on
      the observation of lack of treatment efficacy by farmers. In South Africa one of
      the three populations was found to be resistant to SP and to a phenylpyrazol
      compound (pyriprol). Furthermore, resistance to organosphosphates and SP was
      observed in Australia. Finally, the Larval Tarsal Test proved to be a suitable
      test to evaluate the susceptibility of R. microplus field populations to the most
      relevant acaricidal classes.

PMID- 23540122
TI  - Different blood and sugar feeding regimes affect the productivity of Anopheles
      arabiensis colonies (Diptera: Culicidae).
AB  - The success of the sterile insect technique for the management of mosquito
      populations depends on the release of large numbers of competitive sterile male
      insects. Sustainable mosquito production can only be obtained when proper mass
      rearing equipment and adequate methods are available, including those to feed
      blood to the female mosquitoes. The blood feeding apparatus Hemotek consists of a
      small aluminum plate to which a collagen membrane is fixed and filled with blood
      kept warm by an electric heating element. A larger aluminum plate was developed
      to feed a larger number of female mosquitoes with blood that is kept at a
      constant temperature. The effect of different blood feeding regimes (feeding
      frequency and time the blood is kept in the Hemotek) and sugar deprivation before
      blood feeding on egg production of female Anopheles arabiensis Patton was tested.
      Egg production was higher when blood was offered to the mosquitoes every day as
      compared with every 2 or 4 d. Sugar deprivation for 7 h before blood feeding
      enhanced egg production by 50% compared with female mosquitoes that had
      continuous access to sugar. Neither male nor female survival was impaired.
      Finally, we showed that the same blood could be kept warm and used over several
      hours to feed mosquitoes in multiple cages without any impact on egg production
      or hatch rate. Being able to use the same blood over extended periods would save
      considerable time, handling, and funds.

PMID- 23540123
TI  - Operational use of household bleach to "crash and release" Aedes aegypti prior to
      Wolbachia-infected mosquito release.
AB  - Dengue (family Flaviviridae, genus Flavivirus, DENV) remains the leading
      arboviral cause of mortality in the tropics. Wolbachia pipientis has been shown
      to interrupt DENV transmission and is presently being trialled as a biological
      control. However, deployment issues have arisen on methods to temporarily
      suppress wild mosquito populations before Wolbachia-infected mosquito releases.
      By suppressing wild populations, fewer Ae. aegypti releases are required to
      achieve a sustainable Wolbachia density threshold. Furthermore, public distress
      is reduced. This study tests the application of domestic bleach (4% NaCIO) to
      temporarily "crash" immature Aedes populations in water-filled containers. Spray
      application NaClO (215 ppm) resulted in a mean 48-h mortality of 100, 100, 97,
      and 88% of eggs, second-instar larvae, fourth-instar larvae, and pupae,
      respectively. In the field, NaClO delayed ovipositing by 9 d in cooler months,
      and 11 d in hotter months, after which oviposition resumed in treated
      receptacles. We found bleach treatment of pot-plant bases did not cause wilting,
      yellowing, or dropping of leaves in two ornamental plants species. Domestically
      available NaClO could be adopted for a "crash and release" strategy to
      temporarily suppress wild populations of Ae. aegypti in containers before release
      of Wolbachia-infected mosquitoes. The "crash and release" strategy is also
      applicable to other mosquito species, e.g., Aedes albopictus (Skuse), in
      strategies using released mosquitoes.

PMID- 23540124
TI  - Insecticide resistance in two Aedes aegypti (Diptera: Culicidae) strains from
      Costa Rica.
AB  - Dengue (family Flaviridae, genus Flavivirus, DENV) and dengue hemorrhagic fever
      (DHF) are presently important public health problems in Costa Rica. The primary
      strategy for disease control is based on reducing population densities of the
      main mosquito vector Aedes aegypti (L.) (Diptera: Culicidae). This is heavily
      dependent on use of chemical insecticides, thus the development of resistance is
      a frequent threat to control program effectiveness. The objective of this study
      was to determine the levels of insecticide resistance and the metabolic
      resistance mechanisms involved in two Ae. aegypti strains collected from two
      provinces (Puntarenas and Limon) in Costa Rica. Bioassays with larvae were
      performed according to World Health Organization guidelines and resistance in
      adults was measured through standard bottle assays. The activities of beta
      esterases, cytochrome P450 monooxygenases, and glutathione S-transferases (GST),
      were assayed through synergists and biochemical tests, wherein the threshold
      criteria for each enzyme was established using the susceptible Rockefeller
      strain. The results showed higher resistance levels to the organophosphate (OP)
      temephos and the pyrethroid deltamethrin in larvae. The efficacy of commercial
      formulations of temephos in controlling Ae. aegypti populations was 100%
      mortality up to 11 and 12 d posttreatment with daily water replacements in test
      containers. Temephos and deltamethrin resistance in larvae were associated with
      high esterase activity, but not to cytochrome P450 monooxygenase or GST
      activities. Adult mosquitoes were resistant to deltamethrin, and susceptible to
      bendiocarb, chlorpyrifos, and cypermethrin. Because temephos and deltamethrin
      resistance are emerging at the studied sites, alternative insecticides should be
      considered. The insecticides chlorpyrifos and cypermethrin could be good
      candidates to use as alternatives for Ae. aegypti control.

PMID- 23540125
TI  - Permethrin resistance in Aedes albopictus (Diptera: Culicidae) and associated
      fitness costs.
AB  - Insecticide resistance has become a serious issue in vector management programs.
      Information on insecticidal resistance and its associated mechanisms is important
      for successful insecticide resistance management. The selection of a colony of
      permethrin-resistant Aedes albopictus (Skuse) (Diptera: Culicidae), originating
      from Penang Island, Malaysia, yielded high larval-specific resistance to
      permethrin and cross-resistance to deltamethrin. Synergism assays showed that the
      major mechanism underlying this resistance involves cytochrome P450
      monooxygenase. The resistance is autosomal, polygenically inherited and
      incompletely dominant (D = 0.26). Resistant larvae were reared under different
      conditions to assess the fitness costs. Under high larval density, larval
      development time of the resistant SGI strain was significantly longer than the
      susceptible VCRU strain. In both high- and low-density conditions SGI showed a
      lower rate of emergence and survival compared with the VCRU strain. Resistant
      larvae were more susceptible to predation by Toxorhynchites splendens (Wiedemann)
      (Diptera: Culicidae) larvae. The body size of SGI females reared under high
      density conditions was larger compared with females of the susceptible strain.
      SGI females survived longer when starved than did VCRU females. The energy
      reserve upon eclosion was positively correlated with the size of the adults.

PMID- 23540126
TI  - Experimental and natural vertical transmission of West Nile virus by California
      Culex (Diptera: Culicidae) mosquitoes.
AB  - Culex (Diptera: Culicidae) mosquitoes, the primary summer vectors of West Nile
      virus (family Flaviviridae, genus Flavivirus, WNV), also may serve as
      overwintering reservoir hosts. Detection of WN viral RNA from larvae hatched from
      eggs deposited by infected females during late summer and fall may provide
      evidence for the vertical passage of WNV to overwintering cohorts. To determine
      whether vertical transmission to the overwintering generation occurs in
      populations of Culex mosquitoes throughout California, larvae from naturally
      infected females were tested by family for WN viral RNA by real-time quantitative
      reverse transcription-polymerase chain reaction during August through October
      2011. Viral RNA was detected in 34 of 934 Culex tarsalis Coquillett and Cx.
      pipiens complex females that laid viable egg rafts. From these egg rafts, first
      instar larvae from nine families tested positive, yielding an overall field
      vertical transmission rate of 26% (n = 34). To determine whether the WNV may be
      lost transtadially during development to the adult stage, first-instar larvae and
      adult progeny from experimentally infected Cx. pipiens complex females were
      assessed for the presence and quantity of WN viral RNA. Most (approximately 75%)
      WNV infections were lost from positive families during larval development to the
      adult stage. In field and laboratory studies, only infected mothers with mean
      cycle threshold scores < or = 20 vertically transmitted WNV to larval progeny,
      adult progeny, or both. In summary, vertical transmission of WNV was detected
      repeatedly in naturally infected Culex mosquitoes collected throughout California
      during late summer and fall, with females having high titered infections capable
      of passing WNV onto their progeny destined for overwintering.

PMID- 23540127
TI  - Detection of Babesia microti and Borrelia burgdorferi in host-seeking Ixodes
      scapularis (Acari: Ixodidae) in Monmouth County, New Jersey.
AB  - The etiological agents that cause human babesiosis (Babesia microti) and Lyme
      disease (Borrelia burgdorferi) share a common tick vector (Ixodes scapularis Say)
      and rodent reservoir (Peromyscus leucopus), but because the geographical
      distribution of babesiosis is more restricted than Lyme disease, it was not
      considered a nationally notifiable disease until 2011. Although recent studies
      have shown dramatic increases in the number of cases of babesiosis and expansion
      of its range, little is known about infection and coinfection prevalence of these
      pathogens in the primary tick vector. Of the 478 I. scapularis nymphs collected
      within six Monmouth County, NJ, municipalities between 2004 and 2006, 4.0 and
      10.0% were infected with B. microti and B. burgdorferi, respectively, while 2.9%
      were coinfected. Analysis of the 610 I. scapularis adults collected during the
      same period yielded an infection prevalence of 8.2% for B. microti and 45.2% for
      B. burgdorferi, while 6.2% were coinfected. The potential public health
      importance of these findings is discussed.

PMID- 23540128
TI  - Harvested white-tailed deer as sentinel hosts for early establishing Ixodes
      scapularis populations and risk from vector-borne zoonoses in southeastern
      Canada.
AB  - Due to recent establishment of the blacklegged tick, Ixodes scapularis Say, in
      southeastern Canada, tick-borne zoonoses (Lyme disease, human granulocytotropic
      anaplasmosis, and babesiosis) are of growing concern for public health. Using
      white-tailed deer (Odocoileus virginianus) culled in southwestern Quebec during
      2007-2008, we investigated whether hunter-killed deer could act as sentinels for
      early establishing tick populations and for tick-borne pathogens. Accounting for
      environmental characteristics of culling sites, and age and sex of deer, we
      investigated whether their tick infestation levels could identify locations of
      known tick populations detected in active surveillance, presumed tick populations
      detected by passive surveillance, or both. We also used spatial cluster analyses
      to identify spatial patterns of tick infestation and occurrence of tick-borne
      zoonoses infection in ticks collected from the deer. Adult ticks were found on
      15% of the 583 deer examined. Adult male deer had the greatest number
      (approximately 90%) of adult ticks. Overall, 3, 15, and 0% of the ticks collected
      were polymerase chain reaction (PCR)-positive for Borrelia burgdorferi, Anaplasma
      phagocytophilum, and Babesia microti, respectively. Our statistical analyses
      suggest that sex and age of deer, temperature, precipitation, and an index of
      tick dispersion by migratory birds were significantly associated with tick
      infestation levels. Cluster analysis identified significant clusters of deer
      carrying ticks PCR-positive for A. phagocytophilum, and for deer carrying two or
      more I. scapularis. Our study suggests that hunter-killed deer may be effective
      as sentinels for emerging areas of tick-borne anaplasmosis. They may have limited
      use as sentinels for early emerging I. scapularis tick populations and emerging
      Lyme disease risk.

PMID- 23540129
TI  - Improved chemical control of Chagas disease vectors in the dry Chaco region.
AB  - The effectiveness of two doses of suspension concentrate (SC) pyrethroid
      insecticides in suppressing peridomestic populations of Triatoma infestans (Klug)
      was evaluated in 28 rural communities located in Santiago del Estero province,
      northwestern Argentina, including 388 houses and 1,516 identified sites. Four
      treatments were randomly assigned to peridomiciles within each community: 5% SC
      beta-cypermethrin at standard (S, 50 mg active ingredient [AI]/m2) and double
      dose (2S), and 2.5% SC deltamethrin at standard (D, 25 mg [AI]/m2) and double
      dose (2D). Simultaneously, we assessed the effects of both pyrethroids applied at
      standard doses against domestic infestations. Bug infestation at the site level
      was assessed by timed manual collections with a dislodging agent at baseline, 13
      and 21 mo postspraying (MPS). In domiciles, D and S nearly suppressed all T.
      infestans infestations up to 21 MPS. In peridomestic sites infested before
      interventions, multiple logistic regression analysis showed that site-level
      reinfestation at 13 MPS was significantly lower for treatment 2D (1%) than for
      other treatments, whereas 2S (6%), D (5%), and S (14%) did not differ
      significantly between them. The risk of reinfestation after spraying was
      significantly greater in goat or pig corrals than in other peridomestic ecotopes
      (in which treatments did not differ significantly), and in sites infested before
      interventions than in uninfested sites. The application of SC deltamethrin at
      double dose in goat or pig corrals may suppress T. infestans foci and achieve
      more sustained effects in the dry Chaco.

PMID- 23540130
TI  - 16S rRNA gene-based identification of Elizabethkingia meningoseptica
      (Flavobacteriales: Flavobacteriaceae) as a dominant midgut bacterium of the Asian
      malaria vector Anopheles stephensi (Dipteria: Culicidae) with antimicrobial
      activities.
AB  - Following their transmission from the human to the mosquito with the bloodmeal,
      malaria parasites have to persevere in the mosquito midgut for approximately 1 d.
      During this period the parasites are highly vulnerable to factors of the mosquito
      midgut, including bacteria. We here aimed at determining the microbial diversity
      of gut bacteria of the Asian malaria vector Anopheles stephensi (Liston) during
      development and under different feeding regimes, including feeds on malaria
      parasite-infected blood. 16S rRNA and denaturing gradient gel electrophoresis
      analyses demonstrated an increasing reduction in the microbial diversity during
      mosquito development from egg to adult and identified the gram-negative bacterium
      Elizabethkingia meningoseptica King as the dominant species in the midgut of lab
      reared male and female mosquitoes. E. meningoseptica is transmitted between
      generations and its predominance in the mosquito midgut was not altered by diet,
      when the gut microbiota was compared between sugar-fed and blood-fed female
      mosquitoes. Furthermore, feeds on blood infected with malaria parasites did not
      impact the presence of E. meningoseptica in the gut. Extracts from cultured E.
      meningoseptica were active against gram-positive and negative bacteria and yeast
      and against the blood and gametocyte transmission stages of the malaria parasite
      Plasmodium falciparum Welch. The antimicrobial and antiplasmodial activities of
      E. meningoseptica may account for its dominance in the midgut of the malaria
      vector.

PMID- 23540131
TI  - Spatio-temporal dynamics and preference for type of bait in necrophagous insects,
      particularly native and introduced blow flies (Diptera: Calliphoridae).
AB  - We carried out a year-long survey of insects, using carrion-baited traps in the
      municipality of Campinas and five surrounding municipalities with different
      urbanization profiles, in southeastern Brazil. We studied the spatio-temporal
      variability and preferences for type of bait of three blow fly species that are
      forensically important in Brazil: Chrysomya albiceps (Wiedemann), Chrysomya
      megacephala (F.), and Lucilia eximia (Wiedemann). All three species preferred
      chicken. C. albiceps and L. eximia preferred the urban environment, while C.
      megacephala preferred the rural environment. Calliphoridae, Muscidae, Fanniidae,
      and Sarcophagidae were the most numerous families. No clear seasonal patterns
      could be recognized for the three species. The associations of
      species/municipality, species/environment, and species/bait are discussed from
      the ecological and forensic standpoints.

PMID- 23540132
TI  - Increasing precision in development-based postmortem interval estimates: what's
      sex got to do with it?
AB  - Forensic entomologists typically use either succession models for postmortem
      interval (PMI) estimates or development-based models for minimum PMI (PMI(MIN)
      estimates. Development-based age estimates are calculated with durations of
      immature stadia and can also include morphological data such as larval size. For
      developmental data, the first and second instar stages are typically brief with
      little variation in larval length. The third instar, a much longer stage by
      comparison, is prone to considerable variation. This variation is, in part,
      because of the nonlinear growth during the third instar. There is evidence that
      genetic and environmental factors influence growth curve divergence during this
      stage. We chose to investigate one genetic factor, sex, as numerous insect
      species exhibit sex-specific immature growth patterns. The development rate of
      Lucilia sericata (Meigen) (Diptera: Calliphoridae) males and females is
      considered here. We previously determined the genome sizes of L. sericata and
      found significant sexually dimorphic genome sizes. This difference can be
      exploited to identify larval sex to evaluate male and female immature growth
      curves. A preliminary development study encompassing the third larval instar was
      conducted to compare larval lengths for each sex. Results showed length (P <
      0.0001) and sex (P < 0.01) were statistically significant predictors of age at
      two temperatures (30 and 33.5 degrees C), and that total male development was
      significantly shorter (P < 0.001). These results introduce a new tool, assessment
      of sex-specific growth, that has the potential to reduce noise in PMI(MIN)
      estimates when using third instar larvae.

PMID- 23540133
TI  - Insect arrival pattern and succession on buried carrion in Michigan.
AB  - This study examined pig carcasses buried at two different depths, 30 and 60 cm,
      to determine if insects were able to colonize buried carcasses, when they arrive
      at each depth, and what fauna were present over seven sampling dates to establish
      an insect succession database on buried carrion in East Lansing, MI. Thirty-eight
      pigs were buried, 18 at 30 cm and 20 at 60 cm. Four control carcasses were placed
      on the soil surface. Three replicates at each depth were exhumed after 3, 7, 14,
      21, 30, and 60 d, respectively. One pig also was exhumed from 60 cm after 90 d
      and another after 120 d. Sarcophaga bullata (Parker) (Diptera: Sarcophagidae) and
      Hydrotaea sp. (Diptera: Muscidae) were found colonizing buried carrion 5 d after
      burial at 30 cm. Insect succession at 30 cm proceeded with flesh and muscid flies
      being the first to colonize, followed by blow flies. Insects were able to
      colonize carcasses at 60 cm and Hydrotaea sp. and Megaselia scalaris (Loew)
      (Diptera: Phoridae) were collected 7 d after burial. Insect succession at 60 cm
      did not proceed similarly, instead muscid and coffin flies were the only larvae
      collected. Overall these results reveal postburial interval estimates for
      forensic investigations in mid-Michigan during the summer, depending on climatic
      and soil conditions.

PMID- 23540134
TI  - Seasonal necrophagous insect community assembly during vertebrate carrion
      decomposition.
AB  - Necrophagous invertebrates have been documented to be a predominant driver of
      vertebrate carrion decomposition; however, very little is understood about the
      assembly of these communities both within and among seasons. The objective of
      this study was to evaluate the seasonal differences in insect taxa composition,
      richness, and diversity on carrion over decomposition with the intention that
      such data will be useful for refining error estimates in forensic entomology. Sus
      scrofa (L.) carcasses (n = 3-6, depending on season) were placed in a forested
      habitat near Xenia, OH, during spring, summer, autumn, and winter. Taxon richness
      varied substantially among seasons but was generally lower (1-2 taxa) during
      early decomposition and increased (3-8 taxa) through intermediate stages of
      decomposition. Autumn and winter showed the highest richness during late
      decomposition. Overall, taxon richness was higher during active decay for all
      seasons. While invertebrate community composition was generally consistent among
      seasons, the relative abundance of five taxa significantly differed across
      seasons, demonstrating different source communities for colonization depending on
      the time of year. There were significantly distinct necrophagous insect
      communities for each stage of decomposition, and between summer and autumn and
      summer and winter, but the communities were similar between autumn and winter.
      Calliphoridae represented significant indicator taxa for summer and autumn but
      replaced by Coleoptera during winter. Here we demonstrated substantial
      variability in necrophagous communities and assembly on carrion over
      decomposition and among seasons. Recognizing this variation has important
      consequences for forensic entomology and future efforts to provide error rates
      for estimates of the postmortem interval using arthropod succession data as
      evidence during criminal investigations.

PMID- 23540135
TI  - Environmental factors associated with Phormia regina (Diptera: Calliphoridae)
      oviposition.
AB  - The period of insect activity (PIA) contributes information to estimates of the
      minimum postmortem interval in forensic investigations and begins with blow fly
      attraction and oviposition on a resource such as carrion or a human corpse.
      Incorrectly estimating nocturnal oviposition could alter PIA estimates by up to
      at least 12 h; however, the extent of this difference in PIA would depend on
      environmental and geographic factors. To date, the literature on the extent and
      frequency of blow fly nocturnal oviposition is conflicting. Our objectives were
      as follows: 1) to measure the effects of artificial lighting and beef liver bait
      height above ground on nocturnal and diurnal oviposition, and 2) to monitor
      oviposition through the night on swine carcasses exposed to the environment at
      dusk in different habitats over 3 yr. We documented no consistent nocturnal
      oviposition in any trial using beef liver or on carcasses in different habitats
      and seasons. There were statistically significant effects of light and height of
      bait above the ground on diurnal oviposition of Phormia regina (Meigen) in August
      of 2009, the only month with mean night temperatures > 20 degrees C. In August
      there also was significantly greater diurnal oviposition on liver bait placed on
      the ground compared with bait elevated 1 m. Our results suggest that nocturnal
      oviposition is rare in the natural environment. However, we found enhanced
      diurnal oviposition of P. regina under conditions of ambient temperatures > 20
      degrees C the night before oviposition. Additional studies are needed to better
      understand the ecological mechanisms governing blow fly oviposition important to
      forensic entomology.

PMID- 23540136
TI  - First description of polytene chromosomes in biting midges (Diptera:
      Ceratopogonidae).
AB  - Polytene chromosomes are described from secretory cells in larvae of Forcipomyia
      nigra (Winnertz). They are present in large glandular-trichogen cells at the
      bases of secretory setae and in midgut cells that were observed by transmission
      electron microscopy and light microscopy. Polytene chromosomes, isolated from the
      glandular-trichogen cells using aceto-orcein squash technique, measure 50-200
      microm, have braid-like strands of chromatin and no bands, features that are
      unique within the Culicomorpha.

PMID- 23540138
TI  - Looking forward. How Memorial Hermann Health System innovative approach to
      improved surgical quality and patient safety.

PMID- 23540137
TI  - Nesting bird "host funnel" increases mosquito-bird contact rate.
AB  - Increases in vector-host contact rates can enhance arbovirus transmission
      intensity. We investigated weekly fluctuations in contact rates between
      mosquitoes and nesting birds using the recently described Nest Mosquito Trap
      (NMT). The number of mosquitoes per nestling increased from < 1 mosquito per trap
      night to 36.2 in the final 2 wk of the nesting season. Our evidence suggests the
      coincidence of the end of the avian nesting season and increasing mosquito
      abundances may have caused a "host funnel," concentrating host-seeking mosquitoes
      to the few remaining nestlings. The relative abundance of mosquitoes collected by
      the NMT suggests that significantly more Aedes albopictus (Skuse) and Culex
      pipiens (L.) /restuans (Theobald) sought nesting bird bloodmeals than were
      predicted by their relative abundances in CO2-baited Centers for Disease Control
      and Prevention light and gravid traps. Culex salinarius (Coquillett) and Culex
      erraticus Dyar and Knab were collected in NMTs in proportion to their relative
      abundances in the generic traps. Temporal host funnels and nesting bird host
      specificity may enhance arbovirus amplification and explain observed West Nile
      virus and St. Louis encephalitis virus amplification periods.

PMID- 23540139
TI  - New approaches to liability reform: an introduction.

PMID- 23540140
TI  - AHRQ program promotes patient safety and liability reform.

PMID- 23540141
TI  - Medical mediation: bringing everyone to the table.

PMID- 23540142
TI  - The University of Michigan's early disclosure and offer program.

PMID- 23540143
TI  - New York State shows benefits of CRP demonstration project.

PMID- 23540144
TI  - Health courts may be best cure for what ails the liability system.

PMID- 23540145
TI  - Health courts will not cure all liability ills.

PMID- 23540146
TI  - New directions in liability reform.

PMID- 23540147
TI  - Safe harbors: liability reform for patients and physicians.

PMID- 23540148
TI  - Alternatives to litigation are available: the liability insurer's perspective.

PMID- 23540149
TI  - More emphasis on safety needed: the patient advocate's perspective.

PMID- 23540150
TI  - Attorneys and physicians share common goals: The medical liability lawyer's
      perspective.

PMID- 23540151
TI  - Graduate training for general surgery and the surgical specialties. 1939.

PMID- 23540152
TI  - Statement on firearm injuries.

PMID- 23540153
TI  - The benefits of attending an ACS coding workshop.

PMID- 23540154
TI  - Joint Commission accreditation reaches 20,000 mark.

PMID- 23540155
TI  - NTDB data points: The "fiscal cliff".

PMID- 23540156
TI  - ACS Clinical Scholars-in-Residence Program offers unique research and educational
      opportunity.

PMID- 23540157
TI  - A six-year follow-up study of social network changes among African-American,
      Caribbean, and U.S.-born Caucasian urban older adults.
AB  - This study explores dynamic changes in network size and composition by examining
      patterns of older adults' social network change over time, that is: types of
      movements; the reason for the loss of network members; and the relation of
      movement and composition in concert. This study is a 6-year follow up of changes
      in the social networks of U.S.-Born Caucasian, African-American, and Caribbean
      older adults. One hundred and twenty-four community-dwelling older adults were
      interviewed during 2 data collection points over a 6-year period. Differences
      between Wave 1 and Wave 2 data were examined using paired sample t-tests
      confirmed with post-hoc tests and multivariate analyses. Results regarding types
      of movement showed that network changes were attributed to attrition--the "loss"
      of network members and a novel movement--the "addition" of network members not
      heretofore discussed. The results show an interaction between kinship status,
      ethnicity, and time--the attrition of non-kin members was underscored by ethnic
      differences. The type of network change was specific for type of network
      affiliation, such that children were more likely to be added to the networks of
      the young-old and kin were more likely to be lost in networks of the old-old.
      Older adults engage in social network interactions marked by compensatory
      processes beyond loss of network members such as social promotion and demotion.
      These social network processes are of emotional and functional significance for
      the older adult.

PMID- 23540159
TI  - Walking the red road: the role of First Nations grandparents in promoting
      cultural well-being.
AB  - The purpose of this grounded theory study was to provide a framework for
      understanding the contemporary experience of First Nations grandparents. Fifteen
      respondents (N = 15) were selected from two demographically different Canadian
      cities. Seven of the grandparents lived with their child and a grandchild or
      grandchildren at the time of the interview; an additional four had lived with
      their grandchildren at some point prior to this investigation. Results revealed
      that First Nations grandparents had leveraged their own experiences of cultural
      disruption to reinvest in the cultural health and well-being of their
      grandchildren. One grandfather described this role as "walking the red road"
      which entailed a responsibility "to provide wisdom- and ... protection."
      Identified benefits of rejuvenating traditions and grandparent involvement
      included cultural healing and joy.

PMID- 23540158
TI  - Forgiving and feeling forgiven in late adulthood.
AB  - Enright and colleagues (1996) emphasized the beneficial effect of experiencing
      forgiveness across multiple domains. We build upon their conceptualization of
      forgiveness by adding a domain--forgiveness by God--to create global forgiveness.
      In the current study, we use data from a nationally representative study, the
      Religion, Aging and Health Survey, which utilizes the responses of 1208 Blacks
      and Whites. The results from a latent variable model indicated that both Blacks
      and women were more likely to participate in organized religion, and this
      participation was associated with feeling closer to God. In turn, feeling closer
      to God corresponded to higher levels of global forgiveness but was not directly
      associated with improved-well-being. Instead, it was global forgiveness that
      mediated the relationship between closeness to God and improved well-being.

PMID- 23540160
TI  - A death in the family: death as a Zen concept.
AB  - This study is based on original research that explored family reaction to the
      death of an elderly husband and father. We interviewed 34 families (a family
      included a widow and two adult biological children) approximately 6 to 10 months
      after the death. In one-on-one interviews, we discussed family members' initial
      reaction to the death, how the family is coping with the loss, and the changes
      that occurred in family relationships. In this article we focus on family
      solidarity after the loved one's death and discuss one extended case from the
      larger study. In reviewing our data, we find that a Zen perspective is useful in
      understanding the effect of the death on family relationships because this
      perspective incorporates a focus on the paradoxes of life and death. As death
      forces the family into the "present in its fullness," the contradictions of
      intimacy and distance, past and future, and life and death, emerge. Members of
      the family explore existential questions about life, death, and intimacy, in
      order to find meaning in: 1) the life and death of the loved one; 2) their own
      lives; and 3) the family.

PMID- 23540161
TI  - Treatment of ectopic pregnancy with methotrexate.
AB  - The aim of the present study was to analyze retrospectively the safety and
      success rates of single- and two-dose methotrexate (MTX) protocols for the
      treatment of hemodynamically stable cases of ectopic pregnancy at University
      Department of Gynecology and Obstetrics, Zagreb University Hospital Center,
      during a five-year period. The study evaluated MTX treatment efficacy in 35 women
      with ectopic pregnancies in relation to the initial levels of human chorionic
      gonadotropin (hCG) and progesterone. Successful treatment was recorded in 32/35
      women, 24/25 on single dose MTX and 8/10 on double dose MTX, whereas 3/35
      patients underwent laparoscopy. The mean initial hCG level in all 35 patients on
      day 0 was 657.54 +/- 592.4 IU/L; 572.99 +/- 488.10 IU/L in those successfully
      treated with MTX and 1560.30 +/- 890.70 IU/L in those requiring additional
      laparoscopy (p < 0.005). The mean initial hCG level was 393.10 +/- 305.9 IU/L in
      patients successfully treated with a single dose of MTX and 973.5 +/- 722.40 IU/L
      in those with an additional dose of MTX (p < 0.002). The mean initial
      progesterone level was 16.36 +/-10.70 nmol/L in 35 MTX-treated ectopic pregnancy
      patients, 13.64 +/- 8.89 nmol/L in those with treatment success and 28.45 +/-
      11.32 nmol/L in cases of treatment failure (p < 0.05). The mean level of
      progesterone on day 0 was 12.74 +/- 830 nmol/L in patients successfully treated
      with a single dose of MTX and 26.10 +/- 18.80 nmol/L in patients treated with
      double-dose MTX (p < 0.006). It is concluded that pretreatment values of hCG and
      progesterone are inversely related to medicamentous treatment success in selected
      cases ofhemodynamically stable patients, thus they may be used as an important
      predictor in the management of ectopic pregnancy treated with MTX.

PMID- 23540162
TI  - When to repeat thyroid fine needle aspiration cytology?
AB  - The aim of of the study was to investigate the possible changes of primary fine
      needle aspiration (FNA) diagnoses after subsequent check ups. We investigated 948
      thyroid nodules and the main indications for repeat FNAs were
      inadequate/indeterminate FNA findings and growing nodules at ultrasound check up.
      FNA findings were subdivided into inadequate, benign, low-risk lesion (includes
      cellular follicular lesion, suspicious of follicular/Hurthle cell neoplasm,
      atypical Hurthle cell hyperplasia), follicular/Hurthle cell neoplasm, high-risk
      lesion (includes lesions suspicious of malignancy), and malignant. Of the total
      of 948 nodules, repeat FNA diagnoses remained within the same category in 709
      (75%) nodules. Out of 38 primary inadequate FNAs, 7 (18%) remained inadequate, 24
      (63%) were benign, and 3 (8%) were categorized as high-risk/malignant. Out of 659
      primary benign FNAs, 587 (89%) remained benign, and 11 (2%) were categorized as
      high-risk/malignant. Out of 169 primary low-risk lesion FNAs, 66 (39%) remained
      low-risk, 65 (38%) were benign, and 10 (6%) were categorized as high
      risk/malignant. Out of 43 primary high-risk lesion FNAs, 20 (46%) remained high
      risk, 2 (5%) were benign, 3 (7%) were categorized as a low-risk lesion, and 13
      (30%) were categorized as malignant. Out of 35 FNAs that were primary
      follicular/Hurthle cell neoplasm, 27 (77%) remained follicular/Hurthle cell
      neoplasm, 1 (3%) was categorized as benign, 4 (11%) were categorized as a low
      risk lesion, and 3 (8%) as high-risk/malignant. In conclusion, repeat thyroid FNA
      is useful in most cases of primary inadequate/indeterminate FNA findings, as well
      as in the evaluation of growing nodules.

PMID- 23540163
TI  - Stereological survey of the ameliorative effects of sulforaphane and quercetin on
      renal tissue in unilateral ureteral obstruction in rats.
AB  - Hydrostatic pressure, which is the result of urinary tract blockage, initiates
      renal injuries. The injuries are characterized by tubular dilatation and/or
      atrophy, tubular cell death, inflammatory process and progressive interstitial
      fibrosis with loss of renal parenchyma. The aim of this study was to evaluate the
      ameliorative effects of sulforaphane and quercetin, the two natural compounds
      that can be found in vegetables, in unilateral ureteral obstruction (UUO). Three
      groups of rats underwent surgery to induce UUO. They received distilled water,
      sulforaphane (500 microg/animal/ day) and quercetin (50 mg/kg/day). Stereological
      methods were applied in order to obtain accurate, quantitative and comparable
      data. Less than approximately 4% of renal structures on average remained intact
      in UUO rats. After the treatment of UUO rats with quercetin, approximately 69%,
      32%, 65%, 35% and 41% of the volume of the glomeruli, proximal and distal
      convoluted tubules (PCT and DCT), Henle's loop and collecting ducts remained
      intact, respectively (p < 0.01). After the treatment of UUO rats with
      sulforaphane, approximately 24%, 45%, and 26% of the volume of the PCT, DCT and
      Henle's loop remained intact, respectively (p < 0.01). After the treatment of UUO
      rats with quercetin, approximately 71%, 81%, 51%, and 57% of the length of the
      PCT, DCT, Henle's loop and collecting ducts remained intact, respectively (p <
      0.01). After the treatment of UUO rats with sulforaphane, approximately 42% and
      41% of the length of the PCT and DCT remained intact, respectively (p < 0.01).
      Changes in the length of Henle's loop and collecting ducts were not significant.
      In conclusion, quercetin and sulforaphane were found to be effective in
      preventing some structural renal damage in the direct obstruction model.
      Quercetin had a more ameliorative role on renal structures.

PMID- 23540164
TI  - Multiphase computed tomography of malignant kidney tumors: radiologic-pathologic
      comparison.
AB  - The aim of this retrospective study was to evaluate diagnostic test parameters of
      multiphase spiral computed tomography (CT) of the kidneys in the assessment of
      malignant renal tumors. Fifty-one patient records were reviewed. The imaging
      protocol included unenhanced and postcontrast scans during arterial and
      nephrographic phase. CT findings were compared with pathology findings to assess
      the value of spiral CT (sensitivity, specificity, negative predictive value,
      positive predictive value and accuracy) in the detection and characterization of
      tumors, and in the evaluation of local extension of malignant renal tumors.
      Spiral CT had a 96.08% sensitivity and accuracy in the detection of tumors.
      Characterization of renal tumors with CT had a sensitivity of 94.12% and accuracy
      of 96.08%. In the detection of fibrous capsule penetration, CT reached a
      sensitivity of 91.97% and specificity of 51.28%. In the evaluation of canal
      system propagation, the sensitivity was 100% and specificity 90.70%. CT had a
      sensitivity of 75%, specificity of 95.75% and positive predictive value of 60% in
      the evaluation of regional lymph node involvement. In the detection of the main
      renal vein invasion, CT showed 60% sensitivity and 100% specificity. Spearman's
      rank correlation coefficient between the mean tumor size on CT images and renal
      specimen was 0.916. In conclusion, multiphase spiral CT has satisfactory
      diagnostic parameters in the detection, characterization and evaluation of local
      extension of renal tumors except for detection of the main renal vein invasion.

PMID- 23540165
TI  - The prevalence of idiopathic osteosclerosis and condensing osteitis in Zagreb
      population.
AB  - The aim of this study was to determine the prevalence of idiopathic
      osteosclerosis (IO) and condensing osteitis (CO) in Zagreb patient population
      sample according to age and sex, localization in the jaw, as well as dental
      relationship between IO and CO lesions. A retrospective study was performed using
      orthopantomograms of 1200 patients who underwent dental treatment. Descriptive
      characteristics of radiopacities, including the size and information concerning
      the tooth involved, were recorded and processed using chi2-test. A total of 114
      radiopacities were identified, 34 IO in 29 subjects (16 female and 13 male, mean
      age 35), and 80 CO in 69 subjects (38 female and 31 male, mean age 37). There
      were no significant sex differences. Both CO and IO showed greater predilection
      for occurrence in the premolar to molar region of the mandible. Our results
      indicated a low prevalence of IO and CO in the population of Zagreb. Our findings
      support the theory that IO lesions should be considered developmental variants of
      normal bone architecture unrelated to local stimuli, whereas CO lesions could be
      considered reactive formations related to teeth with deep caries, large
      restoration, or pulpitis.

PMID- 23540166
TI  - Measuring the volume of uterine fibroids using 2- and 3-dimensional ultrasound
      and comparison with histopathology.
AB  - The aim of this study was clinical testing of the reliability and usability of
      three-dimensional (3D) and two-dimensional (2D) ultrasound (US) technology. The
      ultimate aim and purpose of this study was to establish ultrasound methods,
      standards and protocols for determining the volume of any gynecologic organ or
      tumor. The study included 31 women in reproductive age and postmenopause. All
      patients were examined with a RIC 5-9 3D-endovaginal probe (4.3-7.5 MHz) on a
      Voluson 730 Pro ultrasound device. The volume of myomas was measured by using the
      existing 2D and 3D ultrasound methods on the above mentioned device. All patients
      underwent myomectomy or hysterectomy due to clinically and ultrasonographically
      diagnosed uterine myomas indicating operative intervention. After the operation,
      the pathologist determined the volume of removed myomas by measuring them in a
      gauge bowl containing water, i.e. using Archimedes' principle (lift), serving as
      the control group with histopathologic diagnosis. A total of 155 myoma volumes
      were processed on 2D display, 31 myoma volumes were preoperatively measured on 3D
      display and 31 myoma volumes were measured by the pathologist. The values of US
      measurements for each US method were expressed as mean value of all measurements
      of myoma volumes. Statistical processing of the results and Student's t-test for
      independent samples revealed that the 2nd examined US method (measuring of myoma
      by using an ellipse and the longer tumor diameter) and 4th examined US method
      (measuring of myoma by using the longer and shorter tumor diameters together with
      establishing their mean values) in 2D US technique, as well as the 6th examined
      US method in 3D US technique showed no significant measurement differences in
      comparison with control measurement in a gauge bowl containing water (p < 0.05),
      indicating acceptability of the US methods for verifying tumor volumes. The
      standard error in determining the volume of myomas by the above US methods varied
      between 15% and 25%, so it is concluded that these three methods can be used in
      clinical practice to determine tumor volumes, in this case uterine myomas. The 3D
      MultiPlane method proved to be the most reliable method of determining the volume
      of uterine myomas.

PMID- 23540167
TI  - Hypersensitivity to aeroallergens in children with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronically relapsing, inflammatory skin disease
      characterized by severe itch, rash and dry skin. Hypersensitivity to
      aeroallergens is found in 40%-50% of children with AD and it is the cause of
      intensive skin lesions. The aim of the study was to assess the presence of
      hypersensitivity to aeroallergens in AD children. The study included 114 children
      (56 boys and 58 girls), median age 27.5 months, who had been diagnosed with AD
      according to Hanifin and Rajka criteria. The severity of the disease was assessed
      by the SCORAD index. To recognize hypersensitivity to aeroallergens, the
      following parameters were analyzed: medical history, values of absolute
      eosinophil count, total IgE antibodies, specific IgE antibodies to aeroallergens,
      and results of the skin prick test for aeroallergens. A moderate form of the
      disease was present in 61.4% of study children, with a median SCORAD index score
      of 28.5 points; 12.3% of study children showed hypersensitivity to aeroallergens
      (history of hypersensitivity to aeroallergens in 27.2%, increased absolute
      eosinophil count in 53.5%, increased total IgE antibodies in 56.1%, positive skin
      prick test in 20.2%, and positive specific IgE antibodies to aeroallergens in
      12.3% of children). The most common aeroallergens responsible were house dust in
      6.1% and Dermatophagoides pteronyssinus in 3.5% of children with AD.
      Hypersensitivity to aeroallergens was recorded in the same number of children
      with mild and severe forms of the disease and in 5.7% of children with a moderate
      form. In conclusion, the presence of hypersensitivity to aeroallergens in
      children with AD is significant. By discovering and removing the aeroallergens
      responsible, it is possible to achieve reduction in the intensity of skin lesions
      and frequency of exacerbations.

PMID- 23540168
TI  - Quality of life in post-stroke patients: self-evaluation of physical and mental
      health during six months.
AB  - The purpose of this prospective study was to determine the quality of life and
      resocialization of post-stroke patients in the Osijek-Baranya County during six
      months. The study included 161 patients (82 men and 79 women) having sustained
      their first ever acute stroke and being treated at University Department of
      Neurology, Osijek University Hospital Center in Osijek. The Health Survey SF-36
      questionnaire was used for self-evaluation of the patients' physical and mental
      health. Initial assessment was carried out in the acute phase of the disease and
      follow-up assessments were carried out 30, 90 and 180 days post-stroke in patient
      homes. The mean value of physical health measured by SF was 46.1 on initial
      measurement, 37.8 on second, 44.3 on third and 53.0 on fourth measurement. The
      mean value of mental health was 48.0 on initial measurement, 36.6 on second, 44.0
      on third and 48.5 on fourth measurement. The median of total physical health and
      mental health on all measurements was higher in men than in women. Comparison of
      the quality of life areas and the items measured by SF-36 questionnaire according
      to sex and measurements showed statistically significant differences on all four
      measurements in women for all items except for social function (p = 0.669). In
      men, statistically significant differences between the measurements were only
      recorded for the item of physical activity (p = 0.013). Stroke significantly
      impairs the quality of life of affected people. The study showed that the poorest
      results were recorded 30 days of the onset of symptoms, while recovery was
      achieved in six months. Patients affected by stroke who stayed with their
      families considered their physical and mental health better than before stroke.

PMID- 23540169
TI  - The prevalence of human papillomavirus 16 and Epstein-Barr virus in patients with
      oral squamous cell carcinoma.
AB  - It has been suggested that certain viruses such as human papillomaviruses (HPV)
      and Epstein-Barr virus (EBV) might have a role in oral squamous cell carcinoma
      (OSCC). However, results of the published studies are controversial and are
      dependent on the geographic distribution and methods of sampling and sample
      analysis. The aim of this study was to determine the prevalence of HPV 16 and EBV
      in OSCC patients. In 24 patients with OSCC (mean age 59.6 +/- 8.8) and 30
      controls (mean age 49.1 +/- 8.3), 5 mL of blood was collected to determine the
      prevalence of EBV by serologic methods. In addition, swabs were obtained to
      analyze the presence of HPV 16 and EBV by use of polymerase chain reaction.
      Statistical analysis was performed by use of Mann-Whitney test, chi2-test and
      Spearman correlation test. The results of this study showed that there were no
      significant differences between OSCC patients and control subjects according to
      the presence of EBV or HPV 16. Therefore, it can be concluded that the role of
      the aforementioned viruses is less likely in our population of OSCC patients.

PMID- 23540170
TI  - The prevalence of neurocranium injury in children in Brod-Posavina County.
AB  - Head injuries are very common in children and are the most frequent cause of
      disability and death among children. This retrospective study included 350
      children hospitalized for injury of neurocranium over a 5-year period at Dr Josip
      Bencevic General Hospital in Slavonski Brod. Boys were more commonly injured
      (63.4%) than girls. The most common injuries were recorded in children aged 7-14
      (47.1%), followed by those aged 1-6 (33.8%) years. The injuries occurred slightly
      more often in urban (50.9%) than in rural (46.6%) setting. Children were more
      commonly injured in the street or on the road (38.6%), followed by injuries
      sustained at home (35.2%), at school (9.3%) and on playgrounds (5.7%). They were
      most commonly injured by fall (50%), followed by traffic injuries (33.5%).
      Statistically significant differences were found in the following age groups: all
      children younger than one year were injured by fall; children aged 1-14 were
      mostly injured by fall (less in traffic, and due to hitting), and those aged 15
      18 mostly in traffic (less by fall and due to hitting). Children were mostly
      injured in the street or on the road (in traffic accidents), followed by injuries
      at home (mostly by fall), at school and around the house or in the yard (mostly
      by fall); on the playground (due to hitting) and on the road (in traffic
      accidents) (statistically significant difference). Most of them had head
      contusion and cerebral commotion combined (46.8%), followed by head contusion
      alone (12.5%) and skull fractures (10.5%). Hemorrhages and hematomas were rare
      (epidural, subdural, subarachnoid hemorrhage), found in 3.2% of cases. We hope
      that our results will prove helpful in planning preventive measures and treatment
      of injured children.

PMID- 23540171
TI  - Group B streptococci urine isolates and their antimicrobial susceptibility
      profiles in a group of Iranian females: prevalence and seasonal variations.
AB  - Streptococcus agalactiae is one of the uropathogens responsible for urinary tract
      infections (UTI) in children, pregnant women, and elderly people with chronic
      underlying diseases. This study was performed to determine the prevalence of
      urinary tract isolates of group B streptococci (GBS) in a group of females
      referred to a referral University Hospital in Iran. In this retrospective cross
      sectional study, urine analysis and urine culture results of all female subjects
      referred to the laboratory of the Rasoul-e-Akram Hospital, Tehran, Iran in 2010
      were reviewed. Bacteriuria, colony count, pyuria and demographic data of patients
      were also evaluated. In this study, 10,256 females were investigated; 2061
      (20.1%) of them had positive urine cultures. GBS was the isolated microorganism
      in 184 (8.92%) cases, yielding a prevalence of 1.79% in total study population.
      The mean age of subjects with positive GBS cultures was 48.24 +/- 18.8 years,
      with a higher prevalence recorded in the 51-60 and 21-30 age groups. The highest
      rates of cultures positive for GBS were seen in December and January. GBS was
      found to be sensitive to the following antibiotics: cephalothin (100%),
      norfloxacin (96.9%), ampicillin (96%), nitrofurantoin (95.5%), and vancomycin
      (95%). In this study, GBS showed greatest resistance to tetracycline (81.6%) and
      co-trimoxazole (68.9%). In conclusion, the prevalence of GBS in females with
      suspected UTI is relatively low; however, attention to the age and susceptibility
      pattern of antibiotic treatment for UTI caused by this microorganism is
      necessary.

PMID- 23540172
TI  - The immune system and overtraining in athletes: clinical implications.
AB  - The primary objective of this review is to provide an overview of how
      overtraining and the overtraining syndrome (OTS) affect the immune system of
      athletes. A secondary objective is to provide sports medicine clinicians with
      guidance as to how best to prevent and/or treat some of the health consequences
      of overtraining and the OTS as related to the development of a compromised immune
      system associated with exercise training. The OTS is a physically debilitating
      condition that results in athletes being totally compromised in their capacity to
      perform and compete. Many physiological systems are affected by the process of
      overtraining and the OTS; but one system in particular, the immune, is highly
      susceptible to degradation resulting in a reduction in overall health and
      performance. Monitoring of an athlete's exercise training load and other life
      stresses is critical to the determination of when their training regimen may be
      excessive, thereby increasing the risk of OTS developing. Taking steps to
      mitigate prolonged exposure to extreme stress (training + life or otherwise) in
      athletes as well as promoting a healthy immune system can significantly aid in
      the advancement of an athlete's training regimen progression and ultimate
      physical performance and overall health. In this light, this review provides
      approaches to aid sports medicine clinicians in promoting a healthy immune system
      in athletes.

PMID- 23540173
TI  - Loss of heterozygosity of the APC gene in a case of vestibular schwannoma
      assessed by two intragenetic markers.
AB  - Schwannomas are benign encapsulated tumors of Schwann cells, the main peripheral
      glia cells. The majority of schwannomas arise spontaneously and account for 8% of
      intracranial tumors. Those involving the cerebellopontine angle are schwannomas
      in 90% of cases. A case is presented of the loss of heterozygosity of the
      adenomatous polyposis coli (APC) gene in a female patient with cranial schwannoma
      from Croatia. The observed change of the APC gene was investigated by use of two
      intragenetic markers. In the light of novel findings on merlin connection to the
      wnt signaling reported in the literature, the finding of gross deletion in a
      patient with cranial vestibular schwannoma is a relevant genetic event.

PMID- 23540174
TI  - Strumal carcinoid of the ovary: report of two cases.
AB  - Primary carcinoid tumors of the ovary account for 5% of ovarian teratomas. They
      are frequently components of mature cystic teratomas or, less commonly, mucinous
      cystadenomas. Most tumors are seen in peri- or postmenopausal women with symptoms
      of enlarging mass, or are incidental findings. Microscopically, there are four
      major variants of ovarian teratomas of carcinoid type: insular, trabecular,
      strumal and mucinous. One-third of patients with the insular type of carcinoids
      have symptoms of the carcinoid syndrome. Strumal carcinoid is an unusual form of
      ovarian teratoma composed of an intimate admixture of thyroid and carcinoid
      tissues that vary in their relative proportions. Two patients with ovarian tumors
      showing typical morphology of primary ovarian strumal carcinoid are described.

PMID- 23540175
TI  - Arachnoid cyst as the cause of bipolar affective disorder: case report.
AB  - This report presents the course of diagnostic examinations and treatment of a 20
      year-old man with bipolar affective disorder for which an organic basis was
      demonstrated. Computed tomography of the brain revealed an arachnoid cyst that
      was surgically treated. The patient underwent both psychiatric and neurosurgical
      treatment. After two-year follow-up and medicamentous treatment prescribed, the
      patient was symptom-free requiring no psychopharmacotherapy for the next 5.5
      years. His overall life functioning is normal, with no signs of disease.

PMID- 23540176
TI  - Endoscopic treatment of the external snapping hip syndrome: surgical technique
      and report of two cases.
AB  - Snapping hip or coxa saltans is a condition characterized by an audible and/or
      palpable snapping during hip movement and can be associated with pain around the
      hip. There are various causes of this condition and can be divided into two
      types: extra-articular and intra-articular. The most common type is the external
      extra-articular, where the snapping is due to thickened posterior part of the
      iliotibial band or anterior part of the gluteus maximus muscle sliding over the
      greater trochanter during hip movement. Two patients with external snapping hip
      are presented, who were treated with our original endoscopic iliotibial band
      release and greater trochanteric bursectomy. There were no surgical complications
      and the patients did not experience snapping or pain in the hip during 24-month
      follow-up period. Results of various open techniques and one endoscopic technique
      in the treatment of external snapping hip are also reported.

PMID- 23540177
TI  - Bifid median nerve in a patient with carpal tunnel syndrome--correlation of
      clinical, diagnostic and intraoperative findings: case report and review of the
      literature.
AB  - A young patient with symptoms of median nerve compression in carpal tunnel
      without known risk factors is presented. Ultrasonography and magnetic resonance
      imaging confirmed an anatomical variation of the median nerve in carpal tunnel,
      described in the literature as bifid median nerve. The knowledge of the existence
      ofbifid median nerve is important in planning surgical decompression of median
      nerve to avoid nerve injury or potential relapse if decompression of both
      branches has not been done. Carpal tunnel ultrasonography is a noninvasive,
      reliable and available diagnostic tool to diagnose bifid median nerve.

PMID- 23540178
TI  - Guidelines for the use of intravenous immunoglobulin in the treatment of
      neurologic diseases.
AB  - The use of intravenous immunoglobulin (IVIg) in the management of patients with
      neuroimmune disorders has shown a progressive trend over the last few years.
      Despite the wide use of IVIg, consensus on its optimal use is deficient. The
      European Federation of Neurological Societies (EFNS) guidance regulations offer
      consensus recommendations for optimal use of IVIg. The effectiveness of IVIg has
      been proven in Guillain-Barre syndrome (level A), chronic inflammatory
      demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level
      A), acute exacerbations of myasthenia gravis and short-term treatment of severe
      myasthenia gravis (level A). As a second-line treatment, the use of IVIg is
      recommended in dermatomyositis in combination with prednisone (level B) and is
      considered as a treatment option in polymyositis (level C). As a second- or even
      third-line therapy, the use of IVIg should be considered in patients with
      relapsing-remitting multiple sclerosis if conventional immunomodulatory therapies
      are not tolerated (level B) and in relapses during pregnancy or post-partum
      period (good clinical practice point). Finally, it appears that the use of IVIg
      has a beneficial effect also in stiff-person syndrome (level A), some
      paraneoplastic neuropathies (level B), and some acute-demyelinating diseases and
      childhood refractory epilepsy (good practice point).

PMID- 23540179
TI  - Twentieth anniversary of the Croatian League Against Rheumatism.

PMID- 23540180
TI  - Surgery for primary intracerebral haemorrhage: is it safe and effective?
AB  - This prospective study was conducted to compare the outcome between medical and
      surgical treatment of primary intracerebral haemorrhage at the department of
      Neurosurgery, Dhaka Medical College Hospital from January 2006 to October 2007.
      All patients with primary intracerebral haematoma with Glasgow Coma Scale (GCS).
      5-15 (on admission) and heamatoma volume 30 cc or above admitted at Neurosurgery
      department managed conservatively or surgically were included in this study.
      Total 60 patients were selected, of them 30 patients managed conservatively and
      30 patients managed surgically. Conservatively managed patients regarded as
      control group (Group-A) and surgically managed patients regarded as experimental
      group (Group-B). Patients or attendants refused to operate were included in the
      conservative group. All the selected patients were evaluated on the basis of
      detailed history, clinical examination (general and neurological examination) and
      CT scan findings. Outcome was evaluated in term of Glasgow Outcome Scale (GOS).
      Best medical treatment was given for conservative group and operations were done
      for surgical group and followed up after surgery till discharge by observing GCS
      and GOS at discharge. Number of death were 15 (50%) patients in group-A and 13
      (43%) patients in group-B. There was no significant difference in mortality rate
      between two groups but outcome was relatively better in group-B. According to
      Glasgow Outcome Scale, dependency in group-A and group-B was 26.6% and 23.4%
      respectively. So dependency were more in group-A. But there was no significant
      difference statistically. Seven (23.4%) patients were independent in group-A but
      10(43.3%) patients were independent in group-B. However in relative terms of
      outcome of group-B was better than that of group-A. In our study we found no
      statistically significant difference in outcome between medical and surgical
      management of primary intracerebral haemorrhage.

PMID- 23540181
TI  - Pattern of urinary tract infection in Kashmir and antimicrobial susceptibility.
AB  - Antibiotic resistance of urinary tract pathogens has increased worldwide. The
      purpose of this study is to provide information regarding the causative agents of
      urinary tract infection in Kashmiri patients, identify the uropathogens
      responsible for the infection and study the antibiotic susceptibility patterns of
      the uropathogens. Clean voided mid-stream urine samples were collected from 2190
      patients. The specimens were cultured and the isolates were identified using
      standard microbiological techniques. The antibiotic susceptibilities of the
      isolates were also determined. Of 2190 specimens, 591 (27%) showed significant
      growth upon culture. Approximately 84.1% (497/591) of the 591 patients with UTI
      were females, most of which belonged to the 21-30 age group (206). The males
      accounted for 15.9% (94/591) UTI cases. Most of the male patients belonged to the
      21-30 age group (34). The lowest incidence of urinary tract infections was seen
      among the 13-20 years age group. Throughout this study males accounted for only
      16% of all UTI cases. Escherichia coli was the most predominant isolate, 53.8%
      followed by Klebsiella pneumoniae 22.4% and Pseudomonas aeruginosa 7.6%. All
      isolates were fully sensitive to ofloxacin, and more than 94% were sensitive to
      cefuroxime. Apart from group D Streptococcus, the overall response to ampicillin
      by all isolates was less than 15%. The prevalence of multi-resistant Pseudomonas
      aeruginosa in community-acquired urinary tract infections is increasing. All
      Pseudomonas aeruginosa isolates were fully susceptible to cefuroxime and
      ofloxacin. It is recommended that cefuroxime and ofloxacin or both are used in
      the blind treatment of urinary tract infection while awaiting the culture and
      sensitivity results. Concurrent with the necessary shift in the prescription
      pattern, attention should be paid to restriction of antibiotic abuse in the
      community to retard development of further drug resistance.

PMID- 23540182
TI  - Intraoperative serum parathyroid hormone level is an indicator of hypocalcaemia
      in total thyroidectomy patients.
AB  - Postoperative hypocalcaemia is the most frequent and common complication after
      total thyroidectomy. It is necessary to diagnose or to predict hypocalcaemia
      immediately after total thyroidectomy for minimizing complications. A prospective
      observational study was carried out in the Department of Clinical Pathology in
      collaboration with Department of Microbiology & Immunology, Department of
      Surgery, Department of Otolaryngology, Bangabandhu Sheikh Mujib Medical
      University (BSMMU) and Department of Otolaryngology, Dhaka Medical College &
      Hospital (DMC&H), Dhaka, during the period of September 2010 to August 2011 to
      evaluate intraoperative (20 minutes after total thyroidectomy) parathyroid
      hormone (PTH) measurement as a predictor of post thyroidectomy hypocalcaemia.
      Total 65 patients were enrolled in this study those came for total thyroidectomy.
      Postoperative hypocalcaemia developed in 25 cases. Intraoperative PTH was
      assessed and significant correlation was found between intraoperative PTH level
      and development of hypocalcaemia. The sensitivity, specificity, accuracy,
      positive predictive value, negative predictive value of intraoperative serum PTH
      for prediction of post total thyroidectomy hypocalcaemia were 84.0%, 85.0%,
      84.6%, 77.8%, and 89.5% respectively. Because of the high sensitivity,
      specificity and accuracy of intraoperative serum PTH of this study, the early
      prediction of hypocalcaemia could be made by single assay of intraoperative serum
      PTH level at 20 minutes after total thyroidectomy.

PMID- 23540183
TI  - Efficacy of lower cut off value of serum prostate specific antigen in diagnosis
      of prostate cancer.
AB  - Indications of prostate biopsy are high serum prostate specific antigen (PSA)
      value and or abnormal digital rectal examination (DRE) findings. Although serum
      PSA value of 4 ng/ml is the most commonly used threshold for recommending
      prostate biopsy, significant proportion of men harbor prostate cancer even when
      their serum PSA values are less than 4.0 ng/ml. Therefore present study was
      designed to determine the performance status of serum PSA in lower cut-off
      values. This hospital based prospective study was conducted in the Department of
      Urology of Bangabandhu Sheikh Mujib Medical University (BSMMU) and Comfort
      Nursing Home Pvt. Ltd, Dhaka from July 2009 to October 2010. Two hundred six male
      patients aged over 50 years having lower urinary tract symptoms (LUTS) and serum
      PSA more than 2.5 ng/ml were prepared for prostate biopsy. Trans rectal
      ultrasound (TRUS) guided biopsy was done. The test statistics used to analyze the
      data were descriptive statistics, sensitivity, specificity, positive and negative
      predictive value, ROC curve. For all analytical tests, the level of significance
      was set at 0.05 and p < 0.05 was considered significant. In 2.5-4 serum PSA
      range, 28.26% (13 out of 46) of all malignancy were found, which would be missed
      if we take cut off value 4. At 2.5 PSA cut-off, Sensitivity 91.3%, Specificity
      14.37%, PPV 23.46%, NPV 85.18%, Efficacy 31.55%. At 4 PSA cut-off value,
      Sensitivity 71.73%, Specificity 46.25%, PPV 27.73%, NPV 85.05%, Efficacy 51.94%.
      So it can be concluded that, for early diagnosis of prostate cancer cut-off value
      of serum PSA of 2.5 ng/ml can be recommended as an indication for prostate
      biopsy.

PMID- 23540184
TI  - Pattern of cutaneous tuberculosis among children and adolescent.
AB  - Cutaneous tuberculosis is one of the most subtle and difficult diagnoses for
      dermatologists practicing in developing countries. It has widely varied
      manifestations and it is important to know the spectrum of manifestations in
      children and adolescent. Sixty cases (age < 19 years) of cutaneous tuberculosis
      were included in this one period study. The diagnosis was based on clinical
      examination, tuberculin reaction, histopathology, and response to antitubercular
      therapy. Histopahology revealed 38.3% had skin tuberculosis and 61.7% had
      diseases other than tuberculosis. Among 23 histopathologically proved cutaneous
      tuberculosis, 47.8% had scrofuloderma, 34.8% had lupus vulgaris and 17.4% had
      tuberculosis verrucosa cutis (TVC). Most common site for scrofuloderma lesions
      was neck and that for lupus vulgaris and TVC was lower limb. Cutaneous
      tuberculosis in children continues to be an important cause of morbidity, there
      is a high likelihood of internal involvement, especially in patients with
      scrofuloderma. A search is required for more sensitive, economic diagnostic
      tools.

PMID- 23540185
TI  - Community acquired pneumonia in diabetic and non-diabetic hospitalized patients:
      presentation, causative pathogens and outcome.
AB  - Both community acquired pneumonia (CAP) and diabetes mellitus are common in
      Bangladesh. Though hospitalization of diabetic patients with CAP is increasing,
      data regarding their clinical presentation, microbial characteristics,
      antimicrobial susceptibility and outcome are lacking. This study was aimed at
      finding any difference in clinical presentation, bacterial causes, antimicrobial
      susceptibility pattern of isolated bacteria and outcome in diabetic and non
      diabetic hospitalized patients with CAP. In this study total 47 diabetic and 43
      non-diabetic adult hospitalized patients with CAP were enrolled. Clinical
      presentation of CAP differed in diabetics and non-diabetics. Frequency of
      atypical presentation and CURB-65 score were significantly higher in diabetics.
      Pleural effusion with multilobar infiltration was also common feature for CAP in
      diabetic patients. Klebsiella pneumoniae was the most frequent causative pathogen
      for CAP in diabetic patients, whereas Streptococcus pneumoniae was the most
      frequent causative agent for non-diabetic patients. Bacteria isolated from sputum
      sample of diabetic patients with CAP were resistant to almost all recommended
      antibiotics used for CAP but 100% of isolates were sensitive to Carbapenems.
      Pulmonary complications were relatively more in diabetics than in non-diabetics.
      Hospitalized diabetics with CAP required referral to intensive care unit more
      than that of non-diabetics. So, diabetic patients with CAP need extra attention.

PMID- 23540186
TI  - Hepatitis B surface antigen-negative, but HBV DNA-positive patients in
      Bangladesh.
AB  - Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B
      virus (HBV) infection in Bangladesh and most other developing countries. However,
      some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may
      cause HBV infection in recipients. HBV DNA was checked in 20 patients with
      cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without
      any known etiology, and 10 apparently healthy subjects with elevated levels of
      serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients
      with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma,
      and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them
      were negative for HBsAg in the sera. This study indicates that some additional
      mechanisms should be developed for detection of HBsAg-negative HBV-infected
      subjects for efficient control and management of HBV infection in Bangladesh.

PMID- 23540187
TI  - Prevalence and risk factors for gastro-esophageal reflux disease in the North
      Eastern part of Bangladesh.
AB  - Despite a common disorder population-based data on gastro-esophageal reflux
      disease (GERD) in Bangladesh is lacking. This epidemiological study was designed
      to determine the prevalence of GERD and its association with lifestyle factors.
      This population-based cross-sectional study was done by door to door interview of
      randomly selected persons in both urban and rural areas of North Eastern part of
      Bangladesh by using a validated questionnaire. A cutoff point 3 was chosen as a
      valid and reliable scale to confirm GERD. Statistical analysis was done by SPSS
      12 version and the level of significance was set at P < or = 0.05. A total of
      2000 persons with an age range of 15 to 85 years were interviewed; 1000 subjects
      from urban area and 1000 from rural area. Among the study subjects 1064 were male
      and 936 were female. A total of 110 persons (5.5%) were found to have GERD
      symptoms and among them 47 were men and 67 were women. The monthly, weekly and
      daily prevalence of heart-burn and or acid regurgitation was 5.5%, 5.25% and 2.5%
      respectively. Female sex, increased age and lower level of education were
      significantly associated with GERD symptoms. Prevalence was found more among city
      dwellers (approximately 6.0% versus 4.8%), married (6.23%, n = 86),
      widowed/widowers (16.83%, n = 17) and day labourer (8.78%). Level of education
      inversely influenced the prevalence. No significant association of GERD was found
      with body mass index (BMI) and smoking. Prevalence of GERD in North-Eastern part
      of Bangladesh was lower than that of western world. Prevalence was found higher
      in urban population, women, married, widowed/widowers and in poor an dilliterate
      persons. BMI and smoking had no significant association with GERD.

PMID- 23540188
TI  - Serotype and serovar distribution of Neisseria gonorrhoeae isolated from high
      risk populations in Bangladesh.
AB  - Neisseria gonorrhoeae, the causative agent of gonococcal infection, is known to
      frequently change their characteristics to evade host immune mechanism.
      Characterization of the clinical isolates of the organism can lead to
      identification of the circulating strains and often a sexual network in a
      community to help in designing the control strategy. Keeping in mind the above
      consideration, a total of 239 N. gonorrhoeae, isolated from high-risk
      populations, were characterized for serotypes and serovars by monoclonal
      antibodies against protein 1 of the organism. Majority of the serotypes were
      serotype B (142, 59.4%). Majority of the isolates showing resistance to at least
      one of the antibiotics tested were also serotype B (139, 59.2%), whereas,
      majority of the isolates showing resistance to any three of the antibiotics
      (multidrug resistant, MDR) (63%) was serotype A. A total of 41 different serovars
      were also identified and five of which (Arst, Bropt, Bopt, Arost, and Brop)
      included the highest percent (49.3%) of the isolates. Many serovars (23/41,
      56.1%) were new emergent and included 58 (24.3%) of the isolates investigated.
      All of the new serovars were resistant to at least one of the antibiotics tested
      and the highest rate (40/102, 39.2%) was MDR. Serotyping and serovar
      determination was found contributory to understand the microepidemics of the N.
      gonorrhoeae isolates. Further studies including antibiogram and contact tracing
      can efficiently help in control of the disease.

PMID- 23540189
TI  - Effect of short-term recombinant human erythropoietin therapy in the prevention
      of anemia of prematurity in very low birth weight neonates.
AB  - Premature infants especially those with birth weight < 1500 g suffer from Anaemia
      of prematurity (AOP) and associated problems. Erythropoietin therapy is a safe
      effective way to prevent and to treat anaemia of prematurity. To evaluate the
      effect of short-term administration of recombinant human erythropoietin (rHuEPO)
      with iron and folic acid in very low birth weight (VLBW) neonates in the
      prevention of anaemia of prematurity. A randomized controlled trial was carried
      out at Dhaka Shishu Hospital. Sixty preterm very low birth weight (PTVLBW) babies
      were enrolled in this study. Thirty were assigned to rHuEPO group and 30 as
      control. Baseline haematologic values were estimated before administration of
      rHuEPO. From day 7 of life rHuEPO-200 IU/kg/dose subcutaneously every alternate
      day for 2 weeks was administered to rHuEPO group. All infants in both groups have
      received oral iron, folic acid from day 14. Clinical and haematological
      assessment was done at 6 and 10 weeks of life. Baseline clinical characteristics
      and haematologic values were almost similar in both groups. This study has shown
      increase in haematological values (haemoglobin and haematocrit) and reduction in
      the number of blood transfusions during both the 1st and 2nd follow up in rHuEPO
      group in comparison to control group (p < 0.01). Short-term rHuEPO appears to be
      very effective in prevention of Anaemia of prematurity.

PMID- 23540190
TI  - [A short essay on the long history of animal hygiene].
AB  - This article gives a review about the history of animal hygiene from its
      beginning thousands of years ago until the present time. Presumably primarily
      developed from a basic food hygiene it always found its way into religious and
      cultural traditions of the different ages all over the world, whereupon animal
      and public hygiene have always been closely related. Additionally animal hygiene
      contributed noticeably to the development of the veterinary system.

PMID- 23540191
TI  - [Impact of atmospheric ammonia on livestock animals--a minireview].
AB  - Ammonia is one of the most important trace gases in the air of livestock
      buildings. Due to its physical and chemical properties and in dependance on the
      exposure conditions ammonia belongs to the irritant gases with a capability to
      have a negative impact on the respiratoy mucosa, the eyes and the skin of animals
      and men. The observed effects are ranging from performance losses over reductions
      of the mucociliary clearance to disturbences of the epithelial homeostasis
      including airway inflammations. Furthermore, some livestock species have shown in
      choice tests their affinity to a low ammoniated environment, where exposure
      concentrations were considerable lower than the threshold limit values fixed in
      animal welfare regulations. It can be expected that ammonia will continously be
      of relevance in future. Therefore, this article gives a short literature-based
      overview about the biological impact of ammonia on poultry, pigs and cattle.

PMID- 23540192
TI  - Tail biting in pigs--causes and management intervention strategies to reduce the
      behavioural disorder. A review.
AB  - One of the largest animal welfare problems in modern pig production is tail
      biting. This abnormal behaviour compromises the well-being of the animals, can
      seriously impair animal health and can cause considerable economic losses. Tail
      biting has a multifactorial origin and occurs mainly in fattening pigs. High
      stocking densities, poor environment and bad air quality are seen as important
      factors. However, it is presumed that a plurality of internal and external
      motivators in intensive pig production can trigger this behaviour which is not
      reported in sounders of wild boars. The aim of this review is to summarize the
      causes and the effects of tail biting in pigs and present management strategies
      that are likely to reduce its incidence. In particular, management strategies by
      applying Precision Livestock Farming (PLF) technologies to monitor and control
      the behaviour of the pigs may be suitable to detect the outbreaks of tail biting
      at an early stage so that counter measures can be taken in time.

PMID- 23540193
TI  - How do pigs behave before starting an aggressive interaction? Identification of
      typical body positions in the early stage of aggression using video labelling
      techniques.
AB  - The aim of this study was to identify, quantify, and describe pre-signs of
      aggression in pigs and the early stages of aggressive interactions. The
      experiment was carried out at a commercial farm on a group of 11 male pigs
      weighing on average 23 kg and kept in a pen of4 m x 2.5 m. In total 8 hours were
      videorecorded during the first 3 days after mixing. As a result, 177 aggressive
      interactions were identified and labelled to find pre-sign body positions before
      aggressive interactions, attack positions and aggressive acts performed from
      these positions. A total of 12 positions were classified as pre-signs (P1-P12)
      and 7 of them were identified immediately at the start of aggressive interactions
      (P6-P12). Most common pre-sign positions were P3-pigs approaching and facing each
      other (24%) and P2-initiator pigs approaching from the lateral side (18%). In 80%
      of the cases the duration of pre-signs was 1-2 sec 72% of all aggressive
      interactions were short (1 to 10 sec). The most frequent attack positions were
      P12-inverse parallel (39.5%), P7-nose to nose, 90 degrees (19.77%) and P9-nose to
      head (13.5%). The most frequent aggressive acts from attack positions were head
      knocking (34.4%), pressing (34.4%) and biting of different body parts (29.4%).
      Head knocking was mostly observed in relation to P7 and P2 positions and biting
      was common in the P7 position. In conclusion, pigs adopt specific pre-signs and
      body positions before the escalation of aggressive interactions. This could be
      used as potential sign to identify a beginning aggression.

PMID- 23540194
TI  - [Effects of sorting weaner pigs by weight on growth performance, aggressive
      interactions and skin lesion score after mixing].
AB  - Weaning piglets at the age of three or four weeks is an integral part of certain
      production rhythms in modern pig farming. Sorting piglets by weight and mixing
      them into new groups is a common method in agricultural practice. The aim of this
      study was to clarify whether the formation of homogeneous weight groups after
      weaning affects weight development and aggressive behaviour. We compared
      homogeneous and heterogeneous weight groups and entire litters that were weaned
      and reared completely. All groups including entire litters were composed of 12
      animals. All piglets were weighed the day before weaning, four days later, and on
      day 38. The number of all aggressive interactions occurring within a group was
      determined by video analysis for 72 hours after mixing.There during four days
      after weaning or over the rearing period. Rearing entire litters resulted in
      significantly higher daily weight gain within four days after weaning and
      throughout the rearing period. Sorting piglets by weight did not affect the
      development of weight dispersion in a group. The coefficients of variation of
      weights in homogeneous and heterogeneous groups which differed significantly at
      the beginning were on a similar level after 38 days. Neither weight balance of
      piglet batches at the end of rearing nor growth performance or aggressive
      interactions were influenced by sorting piglets by weight at weaning.

PMID- 23540195
TI  - The role of bacterial pathogens in coliform mastitis in sows.
AB  - Even in modern piglet production, mastitis and lactation failure in sows
      represent a considerable health problem post partum, affecting in its
      consequences both the sow and her piglets. Known as a multifactorial syndrome,
      Mastitis-Metritis-Agalactia (MMA) has been topic of several studies investigating
      possible influencing factors at farm and sow level in the recent past. However,
      there is a lack of current investigations on the causative pathogens, especially
      with advanced laboratory methods and with an adequate control group of healthy
      animals. Therefore, 1026 milk samples from coliform mastitis (CM)-affected, and
      972 samples from healthy sows on six farms were examined bacteriologically in
      this study. The spectrum of isolated bacteria did not differ significantly
      between diseased and healthy animals for most species, with Escherichia coli as
      predominant species with 70.4% positive samples from diseased, and 78.0% positive
      samples from healthy animals. Furthermore, other Enterobacteriaceae,
      Staphylococcaceae, Streptococcaceae and Enterococcaceae were isolated both from
      CM-affected and non-affected animals.The similar bacteria distribution underlines
      the multifactorial pathogenesis of CM: Only with further adverse--endogen or
      exogen--factors being present, ubiquitous bacteria from the sow's environment can
      contribute to the development of clinical signs of infection.

PMID- 23540196
TI  - [Reduction of livestock-associated methicillin-resistant staphylococcus aureus
      (LA-MRSA) in the exhaust air of two piggeries by a bio-trickling filter and a
      biological three-step air cleaning system].
AB  - "Livestock-associated" Methicillin-resistent Staphylococcus aureus (LA-MRSA) are
      frequently found in the air of piggeries, are emitted into the ambient air of the
      piggeries and may also drift into residential areas or surrounding animal
      husbandries.. In order to reduce emissions from animal houses such as odour,
      gases and dust different biological air cleaning systems are commercially
      available. In this study the retention efficiencies for the culturable LA-MRSA of
      a bio-trickling filter and a combined three step system, both installed at two
      different piggeries, were investigated. Raw gas concentrations for LA-MRSA of 2.1
      x 10(2) cfu/m3 (biotrickling filter) and 3.9 x 10(2) cfu/m3 (three step system)
      were found. The clean gas concentrations were in each case approximately one
      power of ten lower. Both systems were able to reduce the number of investigated
      bacteria in the air of piggeries on average about 90%. The investigated systems
      can contribute to protect nearby residents. However, considerable fluctuations of
      the emissions can occur.

PMID- 23540197
TI  - The potential of a new air cleaner to reduce airborne microorganisms in pig house
      air: preliminary results.
AB  - There is a need for technical solutions to reduce the concentrations of
      bioaerosols in the air and in the exhaust air of livestock buildings. A prototype
      of an air washer combined with a UV-irradiation system was positioned in a
      commercial pig fattening unit to test its efficiency of reducing culturable
      airborne microorganisms. No significant reduction in airborne bacteria and fungi
      was observed when untreated air passed through the device. However, when the air
      washer or the UV-irradiation system was activated, the concentrations of
      mesophilic aerobic bacteria, methicillin resistant Staphylococcus aureus and
      mesophilic aerotolerant cocci were reduced significantly (p < 0.01). Washing the
      air reduced bacteria by 84 to 96% and the relative reduction due to UV
      irradiation ranged between 55 and 90%. The highest relative reduction in airborne
      bacteria (90 to 99%) was detected when the air washer and the UV-irradiation
      systems were in simultaneous operation. The concentration of total airborne fungi
      was reduced significantly (p < 0.05) only when the air was washed and UV
      irradiated. Although these preliminary results provided significant and
      comprehensible findings, long-term studies are required to assess the efficiency
      of the device in more detail.The combination of air washing and UV-irradiation
      seem to be a useful technique for abating airborne microorganisms within or
      emitting from piggery buildings. However, some technical problems remain, such as
      the deposition of particulate matter on the surface of UV-irradiators and the
      consumption of fresh water by the air washer. These issues must be resolved
      before the system may be implemented for general practice.

PMID- 23540198
TI  - [Effects of stocking density on the behaviour and bodily state of broilers
      fattened with a target liveweight of 2 kg].
AB  - The current investigation is a contribution to the animal welfare debate on
      acceptable stocking densities in broiler chickens. Two stocking densities on
      similar levels as currently legally regulated (35 kg/m2 und 40 kg/m2) and two
      cleary lower stocking densities (18 kg/m2 und 25 kg/m2) were investigated in
      groups of 18 to 42 Lohmann broiler chickens (B) in three batches with each time
      one replication of all stocking densities. Target weight of the broiler chickens
      was 2 kg at 39 or 40 days of age. Mortality, final live weights and activity
      levels were not significantly different between stocking densities. The
      proportion of time birds were sitting/lying increased in general with age from
      about 56% to 82%, probably due to their rapid growth. Nevertheless, at the lower
      stocking densities there was only in single cases. Moreover, significantly more
      footpads showed medium grade alterations under higher density conditions; high
      grade alterations were also different between 35 kg/m2 and 40 kg/m2. Walking
      ability was only different between the lowest and the two higher densities.
      Altogether results reflect behavioural restriction at the higher stocking
      densities with increased risks for footpad alterations and lameness. In order to
      reach clear animal welfare improvements, e. g. in the framework of animal welfare
      labeling, a considerable lowering of the stocking density is consequently one
      important measure. However, this recommendation should be further validated under
      commercial conditions.

PMID- 23540199
TI  - [Planimetric measurement of floor space covered by pullets].
AB  - The available floor space has a strong impact on the execution of various
      behaviours of laying hens. Presently, in Germany detailed requirements on the
      housing of pullets are insufficient. In order to get a first approximation, the
      floor space covered by pullets was determined by the colour contrast planimetric
      method KobaPlan. The measurements on standing and sitting pullets were done on a
      random sample of Lohmann Brown (LB), Lohmann Tradition (LT), Lohmann Selected
      Leghorn (LSL) and Dekalb White (DW) hybrids from the 6th week of life to 18/20
      weeks at regular intervals. The hens were weighed and photographed digitally in a
      specific planimetric box (n = 2600 photographs from pullets in standing and 1360
      in sitting position). Afterwards the KobaPlan software program calculated the
      animal area.The results showed a correlation between floor space covered by the
      pullets in standing position and the live weight (R2 = 0.80-0.96). The mean floor
      space covered by LB and LT at the end of rearing (body weight 1450 +/- 25 g LB
      and 1500 +/- 25 g LT) was 422.4 +/- 41.9 cm2 (LB) and 446.7 +/- 49.0 cm2 (LT)
      stand- ing, respectively 448.0 +/- 51.0 cm2 (LB) and 464.5 +/- 42.6 cm2 (LT)
      sitting. LSL and DW (body weight 1300 +/- 25 g) used 371.0 +/- 41.3 cm2 (LSL) and
      349.3 +/- 26.3 cm2 (DW), respectively in standing and 379.5 +/- 41.2 cm2 (LSL) in
      sitting position. Maximum stocking density recommendation for pullets based on
      these planimetric results compared with the space allowance in alternative
      housing systems for laying hens are between eleven and 14 birds/m2. To verify
      this stocking density recommendation for pullets further studies should be
      complemented by specific ethological observations.

PMID- 23540200
TI  - [Discussion of actual legal minimum requirements for feeder space and perch
      length in laying hen husbandry in the light of the body widths measured in
      Lohmann Selected Leghorn and Lohmann Brown laying hens].
AB  - Legal requirements on space and dimensions regarding furnished cages and
      alternative systems in laying hen husbandry are subject of constant discussion.
      Further knowledge about basic measures of the hens might help to come to
      reasonable results in the future. Digital images of Lohmann Selected Leghorn
      (LSL) and Lohmann Brown (LB) laying hens, housed at the Lehr- und Forschungsgut
      Ruthe, University for Veterinary Medicine Hanover, Foundation, in Big Dutchman
      Eurovent laying hen cages, were made at three stages (19th, 36th and 58th week)
      of production. All hens had been taken out of their cages by night and set on a
      perch in a special cage used to photograph the hens frontally under controlled
      conditions. Body widths were calculated by a python application Cdisto.py0 2009
      Andreas Briese) to mark and measure the body width in the digital images of a
      total of 156 hens. Mean body widths of 133.77 mm in Lohmann-LSL hens (SD = 9.71;
      N = 64; mean weight: 1.73 kg) and of 152.55 mm in Lohmann-LB hens (SD = 10.31; N
      = 92; mean weight: 1.93 kg) respectively were found. Even slight changes in body
      weights had no effect on the body width. Nonetheless the differences between both
      hybrids were always statistically significant (Mann-Whitney p < 0,001). Using
      these preliminary results on body width in a mathematical model simultanious
      feeding behaviour becomes only possible if the number of animals is reduced by
      10.3% to 89.7% in LSL and by 21.3% to 78.7% in LB breeds in relation to a
      calculated maximum on base of the minimum space requirements for furnished cages
      in the EU-Dir 74/1999/EC.

PMID- 23540201
TI  - [Distribution of diagnoses in cattle farms in the Middle Weser Area based on the
      analysis of veterinary diagnostic data subject to documentation by law].
AB  - The aim of this study was the evaluation of animal health recording data based on
      veterinary diagnostic data subject to documentation by law from the year 2009.
      Based on this, the occurence of diagnosed cattle diseases in the Middle Weser
      Area was assessed. Analysis was performed for each age category milk cows,
      heifers and calves. Data was provided by three veterinary practices and included
      8919 medicamental treatments on 118 cattle farms. First treatments against 29
      different cow-, 23 heifer- and 18 calf-diseases were documented. Besides the
      single consideration of each documented diagnose, diagnoses were pooled into
      groups ot diagnoses for each age category. The three most common groups allowed a
      good insight into the diagnosed and treated diseases. In dairy cows, the
      diagnoses group of udder disases was predominant (31.0%), followed by diseases of
      the locomotion tract (25.4%) and antiparasitic treatments and prophylaxis
      (19.6%). In heifers, the diagnoses group of antiparasitic treatments and
      prophylaxis ranged at first place (83.2%), followed by respiratory diseases
      (6.1%) and diseases of the locomotion tract (4.6%). In calves, most medicaments
      were used for the treatment against respiratory diseases (54.7%), gut diseases
      (30.8%) and fungal skin infections (7.7%). Even though the informative value of
      veterinary diagnostic data has to be regarded critically, this study provided a
      clear picture of the most frequently diagnosed and treated diseases in cattle.
      Especially in the current discussion about the prudent use of veterinary
      medicaments, such analyses enable insights into animal health and conclusions on
      the amount of administered treatments without additional data acquisition. In due
      critical consideration of the disadvantages of such data, they can form the
      background of a digital documentation and integration of animal health
      information.

PMID- 23540202
TI  - Faecal occurrence and emissions of livestock-associated methicillin-resistant
      Staphylococcus aureus (laMRSA) and ESbl/AmpC-producing E. coli from animal farms
      in Germany.
AB  - The occurrence of laMRSA (livestock-associated methicillin-resistant
      Staphylococcus aureus) and extended-spectrum beta-lactamase (ESBL) and/or plasmid
      mediated AmpC beta-lactamase-producing (AmpC) Enterobacteriaceae in healthy
      livestock herds is known for some time.The spread of these bacteria in the
      environment is discussed critically.The object of this study was to determine the
      presence of these microorganisms in faeces of livestock as well as the discussion
      about a potential faecal emission. Therefore, faeces samples from 37 different
      MRSA positive livestock holdings were tested for MRSA. Furthermore, faeces
      samples from 50 farms with an unknown status regarding ESBL/AmpC-producing E.
      coli were screened for those resistant bacteria. LaMRSA was detected in samples
      of turkey (2/5, 40%) and broiler fattening farms (1/4, 25%) as well as in pig
      farms with higher detection frequencies in fattening farms (11/15, 73.3%) than in
      breeding farms (4/12, 33.3%). ESBL/AmpC-producing E. coli was found in all
      investigated eight broiler farms (100%), in nine out of 16 (56.3%) breeding pig
      as well as in six out of 10 (60%) dairy cattle herds and in seven of 16 (43.8%)
      fattening pig holdings. This presents the first detection of ESBL/AmpC-producing
      E. coli originating from healthy pigs, turkeys and broilers in Germany. In
      addition, samples of fertilized field surfaces were studied exemplarily for the
      presence of MRSA (n = 4) as well as ESBL/AmpC-producing E. coli (n = 2).
      Furthermore, slurry samples from four broiler and five pig farms were analysed
      for the latter. Both MRSA and ESBL/ AmpC-producing E. coli could be detected on
      the field surfaces, the last also in slurry samples. Faecal emissions from animal
      husbandry seem to be one possible route for the spread of these resistant
      microorganisms in the environment.

PMID- 23540203
TI  - Separation of single-walled carbon nanotubes by 1-dodecanol-mediated size
      exclusion chromatography.
AB  - A simple, single-column, high-throughput fractionation procedure based on size
      exclusion chromatography of aqueous sodium dodecyl sulfate suspensions of single
      walled carbon nanotubes (SWCNTs) is presented. This procedure is found to yield
      monochiral or near monochiral SWCNT fractions of semiconducting SWCNTs. Unsorted
      and resulting monochiral suspensions are characterized using optical absorption
      and photoluminescence spectroscopy.

PMID- 23540204
TI  - Research on substances with activity against orthopoxviruses.
AB  - Although smallpox was eradicated over 30 years ago, the disease remains a major
      threat. High mortality, high infectivity and low resistance of the contemporary
      population make the smallpox virus very attractive to terrorists. The possible
      presence of illegal stocks of the virus or risk of deliberate genetic
      modifications cause serious concerns among experts. Hence, it is reasonable to
      seek effective drugs that could be used in case of smallpox outbreak. This paper
      reviews studies on compounds with proven in vitro or in vivo antipoxviruses
      potential, which show various mechanisms of action. Nucleoside analogues, such as
      cidofovir, can inhibit virus replication. Cidofovir derivatives are developed to
      improve the bioavailability of the drug. Among the nucleoside analogues under
      current investigation are: ANO (adenozine N1-oxide) and its derivatives, N
      methanocarbothymidine [(N)-MCT], or derivatitives of aciklovir, peninclovir and
      brivudin. Recently, ST-246 - which effectively inhibits infection by limiting
      release of progeny virions - has become an object of attention. It has been also
      been demonstrated that compounds such as: nigericin, aptamers and peptides may
      have antiviral potential. An interesting strategy to fight infections was
      presented in experiments aimed at defining the role of individual genes (E3L, K3L
      or C6L) in the pathogenesis, and looking for their potential blockers.
      Additionally, among substances considered to be effective in the treatment of
      smallpox cases, there are factors that can block viral inhibitors of the human
      complement system, epidermal growth factor inhibitors or immunomodulators.
      Further studies on compounds with activity against poxviruses are necessary in
      order to broaden the pool of available means that could be used in the case of a
      new outbreak of smallpox.

PMID- 23540205
TI  - Effects of spring season solar drying process on sanitation indicators in sewage
      sludge and potential as a method for fertilizer production.
AB  - The agricultural use of sewage sludge is possible on condition of maintaining
      microbiological and parasitological standards, and one of the most modern methods
      improving its sanitary state is solar drying. In the presented study, the effect
      of this process on the elimination of indicator microorganisms (Escherichia coli,
      Salmonella Senftenberg W775, Enterococcus spp.) and eggs of Ascaris suum
      introduced into the biomass of sludge was examined. The experiment was carried
      out in the spring period with a maximal temperature of 18  degrees C inside the
      drying plant. Bacteria and parasite eggs were introduced into special carriers
      (cylinders filled with sewage sludge) and placed at selected points of the drier.
      The carriers were removed every 7 days and subject to a research procedure in
      order to estimate the number of bacteria and percentage of live eggs of Ascaris
      suum. Sanitization of the material was not obtained, since after 28 days of the
      process the final product contained a large concentration of Enterococcus spp.
      and S. Senftenberg W775 (10(5) -10(9) MPNg(-1)). Only the number of E. coli
      decreased by 6 log. During the process, the fastest decrease in the number of
      bacteria was observed in E. coli (ca 0.2 log/day), slower in enterococci (0.02
      0.081 log/day), and the slowest in bacilli of the genus Salmonella (0.011-0.061
      log/day). Sludge after drying also still contained 57-66% of live eggs of A.
      suum. The study proved that the solar drying of sludge in the spring period
      results in a product which poses a hazard for public and animal health and
      environmental sustainability, and should not be used as a fertilizer.

PMID- 23540206
TI  - First detection of microsporidia in raised pigeons in Poland.
AB  - Microsporidia are single-celled intracellular parasites which occur in a number
      of animals, both vertebrates and invertebrates. Several species of microsporidia
      can cause disease in humans in both immunocompromised and immunocompetent
      individuals. However, the sources of human infection and the routes of
      transmission of microsporidia have not yet been fully determined, although more
      and more researchers are of the opinion that microsporidia in humans is zoonotic.
      The aim of the presented study was to identify the most common microsporidial
      species in the droppings of raised and wild pigeons in Poland. A total of 139
      collective samples of droppings (33 samples of droppings from feral pigeons and
      106 samples from raised pigeons) were examined using conventional staining and
      molecular techniques. Using chromotrope staining and multiplex FISH techniques,
      the microsporidial spores were found in 12 (8.6%) of the 139 samples of
      droppings. The spores of Encephalitozoon hellem were detected in five samples of
      pigeon droppings (3.6%), spores of E. intestinalis in four samples of droppings
      (2.9%), while spores of E. cuniculi and E. bieneusi were only detected in two
      samples (1.4%). Furthermore, a mixed infection of E. bieneusi and E. cuniculi was
      found in a single sample of droppings (0.7%). The presence of microsporidial
      spores in droppings collected from raised pigeons indicates a risk of infection
      to humans, mainly pigeon fanciers.

PMID- 23540207
TI  - Air samplings in a Campylobacter jejuni positive laying hen flock.
AB  - The air in laying hen houses contains high concentrations of airborne bacteria.
      The numbers of these bacteria can be influenced by the efficiency of the chosen
      sampling method. In the presented study, AGI-30 Impingers and the Coriolis((r))u
      air Sampler were compared in terms of their efficiency in sampling aerobic
      mesophilic bacteria in a laying hen house. Measurements were conducted in a
      laying hen flock with high prevalences of C. jejuni in order to investigate if
      culturable cells of this organism can also be detected by the applied methods.
      Airborne dust was also analyzed for the presence of C. jejuni specific DNA to
      assess the possible occurrence of non-culturable C. jejuni in the hen house air.
      The numbers of mesophilic airborne bacteria ranged from 8 * 10(4) - 2 * 10(6)
      CFU/m(-3) when sampled using AGI-30 Impingers, and from 2 * 10(5) - 4 * 10(6)
      CFU/m -3 when sampled using a Coriolis((r))u air Sampler. The concentrations
      detected simultaneously by both devices correlated well (rPearson = 0.755), but
      the Coriolis((r))u air Sampler showed a significantly higher sampling efficiency
      (p<0.001). Although, the within flock prevalence of C. jejuni was high during the
      experiments (between 70-93%), neither of the air sampling methods could detect
      culturable C. jejuni from the air. However, C. jejuni specific DNA was detected
      in 15 out of 18 airborne dust samples by mapA PCR. Based on the results, it can
      be concluded that airborne culturable C. jejuni were not detectable, even with an
      efficient air sampler, because of their low concentration. Therefore, the risk of
      airborne infection to poultry workers on inhaling airborne C. jejuni seems
      negligible. Also, the transmission of culturable C. jejuni to neighboring farms
      by the airborne route is unlikely. Otherwise, the detection of airborne C. jejuni
      specific DNA suggests that non-culturable cells could appear in the hen house
      air, and in future it should be verified whether sampling stress of the air
      sampling methods could induce the non-culturable state.

PMID- 23540208
TI  - Assessment of the frequency of different Borrelia burgdorferi sensu lato species
      in patients with Lyme borreliosis from north-east Poland by studying preferential
      serologic response and DNA isolates.
AB  - INTRODUCTION AND OBJECTIVE: Several Borrelia burgdorferi sensu lato species cause
      Lyme borreliosis throughout Europe and their geographic distribution may
      influence clinical manifestations of the disease. In Poland, Lyme borreliosis
      presents mainly with neurologic and cutaneous symptoms, while clinically overt
      arthritis is rare. The presented study investigates the prevalence of B.
      burgdorferi s.l. genospecies in a group of patients with different clinical forms
      and stages of Lyme borreliosis in north-east of Poland. This has not previously
      been studied. MATERIAL AND METHODS: Preferential reactivity towards different
      B.burgdorferi s.l. species was investigated with a previously validated
      immunoblot assay in sera of 33 patients with disseminated Lyme borreliosis: 10
      with neuroborreliosis, 6 with acrodermatitis chronica atrophicans and 17 with
      osteoarticular symptoms. Also typed were B.burgdorferi s.l. DNA isolated from the
      skin and synovial fluid of 7 patients with erythema migrans, acrodermatitis
      chronic atrophicans and arthritis. RESULTS: Preferential reactivity was detected
      in 30 out of 33 serum samples. Of these, 25 reacted preferentially with
      B.afzelii, 3 with B. garinii and 2 with B. burgdorferi ss. B.burgdorferi DNA was
      isolated from all studied samples and typed as B.afzelii in 5. In a patient with
      acrodermatitis chronica atrophicans studied with both methods simultaneously,
      B.afzelii was identified by both genotyping and serotyping. CONCLUSIONS: Both
      methods gave consistent results, indicating B.afzelii as the main agent of all
      the clinical forms of the Lyme borreliosis in the study area.

PMID- 23540209
TI  - Microflora and mycotoxin contamination in poultry feed mixtures from western
      Poland.
AB  - OBJECTIVE: Contamination of feeds with pathogenic microflora and mycotoxins
      constitutes a serious threat both for animals and humans. The aim of the study
      was to determine the degree of risk of the occurrence of microscopic fungi,
      selected bacteria and mycotoxins from the trichothecene group in poultry feeds in
      western Poland. RESULTS: In feed mixtures, the concentration of ergosterol (ERG),
      being a specific quantitative biomarker for the content of microscopic fungi, was
      determined. Grower and finisher feeds were characterized by a higher count of
      bacteria and fungi in comparison to starter feeds. A considerable variation was
      found in the amount of ergosterol in analyzed feeds. Mean ergosterol content in
      feeds amounted to 19.34 mg/kg. The most common genera of fungi detected in the
      tested feeds included Aspergillus, Rhizopus and Mucor. Irrespective of the type
      of feed, the proportion of trichothecenes group B was five times higher than that
      of trichothecenes group A in relation to the total content of these mycotoxins in
      samples. In terms of the analyzed mycotoxins, feeds contained the highest
      concentration of deoxynivalenol (DON). A statistically significant correlation
      was shown between DON and ERG and between total trichothecenes and ERG.
      CONCLUSION: Recorded results indicate that the level of microbiological
      contamination in feeds for broiler chickens produced in western Poland is within
      the requirements of the binding standards.

PMID- 23540210
TI  - Forecasting of the selected features of Poaceae (R. Br.) Barnh., Artemisia L. and
      Ambrosia L. pollen season in Szczecin, north-western Poland, using Gumbel's
      distribution.
AB  - INTRODUCTION AND OBJECTIVES: The allergenic pollen content of the atmosphere
      varies according to climate, biogeography and vegetation. Minimisation of the
      pollen allergy symptoms is related to the possibility of avoidance of large doses
      of the allergen. Measurements performed in Szczecin over a period of 13 years
      (2000-2012 inclusive) permitted prediction of theoretical maximum concentrations
      of pollen grains and their probability for the pollen season of Poaceae,
      Artemisia and Ambrosia. Moreover, the probabilities were determined of a given
      date as the beginning of the pollen season, the date of the maximum pollen count,
      Seasonal Pollen Index value and the number of days with pollen count above
      threshold values. MATERIALS AND METHODS: Aerobiological monitoring was conducted
      using a Hirst volumetric trap (Lanzoni VPPS). Linear trend with determination
      coefficient (R(2)) was calculated. Model for long-term forecasting was performed
      by the method based on Gumbel's distribution. RESULTS: A statistically
      significant negative correlation was determined between the duration of pollen
      season of Poaceae and Artemisia and the Seasonal Pollen Index value. Seasonal,
      total pollen counts of Artemisia and Ambrosia showed a strong and statistically
      significant decreasing tendency. On the basis of Gumbel's distribution, a model
      was proposed for Szczecin, allowing prediction of the probabilities of the
      maximum pollen count values that can appear once in e.g. 5, 10 or 100 years.
      CONCLUSIONS: Short pollen seasons are characterised by a higher intensity of
      pollination than long ones. Prediction of the maximum pollen count values, dates
      of the pollen season beginning, and the number of days with pollen count above
      the threshold, on the basis of Gumbel's distribution, is expected to lead to
      improvement in the prophylaxis and therapy of persons allergic to pollen.

PMID- 23540211
TI  - Silver nanoparticles -- allies or adversaries?
AB  - Nanoparticles (NP) are structures with at least one dimension of less than 100
      nanometers (nm) and unique properties. Silver nanoparticles (AgNP), due to their
      bactericidal action, have found practical applications in medicine, cosmetics,
      textiles, electronics, and other fields. Nevertheless, their less advantageous
      properties which make AgNP potentially harmful to public health or the
      environment should also be taken into consideration. These nanoparticles are cyto
      and genotoxic and accumulate in the environment, where their antibacterial
      properties may be disadvantageous for agriculture and waste management. The
      presented study reviews data concerning the biological effects of AgNP in
      mammalian cells in vitro: cellular uptake and excretion, localization in cellular
      compartments, cytotoxicity and genotoxicity. The mechanism of nanoparticle action
      consists on induction of the oxidative stress resulting in a further ROS
      generation, DNA damage and activation of signaling leading to various, cell type
      specific pathways to inflammation, apoptotic or necrotic death. In order to
      assure a safe application of AgNP, further detailed studies are needed on the
      mechanisms of the action of AgNP on mammalian cells at the molecular level.

PMID- 23540212
TI  - Prevalence of contact allergy in children suffering from atopic dermatitis,
      seborrhoeic dermatitis and in healthy controls.
AB  - INTRODUCTION: Atopic dermatitis is one of the most common skin disorders in
      children. There is only scarce literature data on the prevalence of contact
      allergy in children with atopic dermatitis. OBJECTIVES: To assess the prevalence
      of contact allergy among children with atopic dermatitis, seborrhoeic dermatitis
      and in a population of healthy children. MATERIAL AND METHODS: Patch tests were
      performed in 104 children aged 1-20 years treated for atopic dermatitis in the
      Department of Dermatology, University of Medical Sciences, Poznan, and also in 2
      control groups: 15 subjects with seborrhoeic dermatitis (15-20 years) and 36
      healthy children (1-20 years). RESULTS: In children with atopic dermatitis,
      contact allergy was observed in 47/104 patients (45.2%). With regards to the 3
      age subgroups, positive patch test results were detected in 30/43 in children
      aged 1-5 years (69.8%), 13/36 in children aged 6-14 years (36.1%) and in 4/25
      adolescents 15-20 years of age (16%). The highest proportion of positive patch
      tests was detected in the youngest subgroup of healthy children. Comparative
      analysis revealed type IV hypersensitivity statistically significantly more
      frequent in children with atopic dermatitis than in the 2 control groups.
      CONCLUSIONS: The statistically significant positive results in the highest
      proportion of patch tests in the youngest age subpopulation of children with
      atopic dermatitis, and detection of contact allergy most commonly in the youngest
      subgroup of healthy children, may suggest nonspecifically positive results
      associated with the immaturity of the epidermal barrier during the first years of
      life. Concentrations of contact allergens included in current pediatric sets of
      patch tests seems to be too high and should be verified.

PMID- 23540213
TI  - Analyses of hospitalization of diabetes mellitus patients in Poland by gender,
      age and place of residence.
AB  - AIM: The purpose of this study was to analyze the hospitalization of diabetes
      mellitus patients in Polish hospitals in 2005-2009. MATERIALS AND METHODS: Data
      was taken from a nationwide database, kept at the National Institute of Public
      Health - National Institute of Hygiene in Warsaw. Data gathered for this work
      related to patients whose main cause of hospitalization was diabetes. RESULTS: In
      the period of five years the number of diabetes-caused hospitalizations increased
      by nearly 22% - from 172.2 per 100 thousand in 2005 to 209.9 per 100 thousand in
      2009. Hospital treatment covered mainly patients suffering from type 2 diabetes
      (116.4 per 100 thousand in 2009), as well as type 1 diabetes (87.6 per 100
      thousand in 2009). Patients under 39 years of age were more often hospitalized
      because of type 1 diabetes, whereas in the older age groups patients were more
      often treated in hospitals for type 2 diabetes. Generally, in both types of the
      disease, older patients required hospitalizations more often than the younger
      ones. Cardiovascular diseases were the most reported co-morbidity in both types
      of the disease. In 2005-2009 the hospital mortality rate decreased with regard to
      both types of diabetes and an average length of hospital stay decreased by one
      day, reaching 8.1 days in 2009. CONCLUSION: It must be emphasized that the
      growing epidemic of diabetes and its complications are an important challenge to
      society. The percentage of people hospitalized due to diabetes is increasing
      every year and consumes significant resources dedicated to health care. Early
      diagnosis and appropriate treatment of diabetes are imperative, as well as
      reducing the disparities in access to medical care (ambulatory and stationary)
      for town and country residences.

PMID- 23540214
TI  - Differences in results of breast cancer curative treatment between urban/rural
      female population in Podlaskie Voivodship of Poland before introduction of the
      National Cancer Control Programme.
AB  - The aim of the study was to evaluate differences in the results of the curative
      treatment received by women with breast cancer in urban and rural area in
      Podlaskie Voivodship in 2001-2002 before the introduction of the National Cancer
      Control Programme. The analysis was based on 449 women with breast cancer, who
      received curative treatment in years 2001-2002. Relative 5-year survival rates as
      function of age and stage among urban and rural women population were calculated.
      The results showed that survival rates in Podlaskie Voivodship among curatively
      treated women with breast cancer were 81.9% but they differed between urban and
      rural areas. Patients living in rural areas had much lower survivals than those
      living in urban areas at local and regional stage of disease. In all age groups
      considered in the study survivals in rural areas were lower than in urban ones in
      which survivals were higher in 55-64 age group. These results indicated the
      necessity intervention in order to increase the access to the health care system
      and effectiveness of early detection and also improved treatment standards for
      more disadvantaged rural areas. These results should be also considered in
      monitoring of the National Cancer Control Programme introduction in Poland in
      2006.

PMID- 23540215
TI  - Reasons for delay in diagnosis and treatment of lung cancer among patients in
      Lublin Voivodeship who were consulted in Thoracic Surgery Department.
AB  - INTRODUCTION: Despite the progress which has been made in the diagnosis and
      treatment of lung cancer, it is still one of the main causes of death in both men
      and women. The introduction of new therapeutic modalities did not improve the 5
      year survival results of lung cancer patients. The Lublin Voivodeship is a
      sparsely-inhabited area with little urbanization and a population of about 2.2
      million people. Only 46.8% of its citizens live in the towns, while the national
      average is 61.9%. OBJECTIVES: The aim of the study was to compare the differences
      in the periods of time and reasons for delay in diagnosis and initiation of
      treatment of lung cancer among patients who are inhabitants of the rural and
      urban regions of Lublin Voivodeship, and who were consulted in Thoracic Surgery
      Department. MATERIALS AND METHODS: 300 lung cancer patients who were consulted in
      the Thoracic Surgery Outpatient Clinic or who were hospitalized in the Department
      of Thoracic Surgery in the period between 2 January 2010 - 7 January 2011 were
      included in the study. Delays were calculated for two periods of time: 1) time
      from the first signs of the disease to the first medical examination; 2) the time
      from the first visit to a doctor to the start of treatment, or disqualification
      from the causative treatment. The time of the first delay for the urban and rural
      populations was similar and ranged from 2-37 weeks and 2-23 weeks, respectively.
      Lack of time and disregard of signs of disease were the most commonly reasons
      given for the first delay among rural residents. The urban population indicated
      fear and lack of time as the main reasons of delay. Assessment of the second
      reason for delay was possible thanks to a specially designed research protocol
      which gathered the main reasons of delay in several subgroups that enabled their
      statistical evaluation. The length of second period was similar for both
      populations. RESULTS: There were no significant differences in the length of the
      time of delay between the two assessed groups. In both groups, delays dependent
      on poor healthcare access were similar. Among rural inhabitants, the most often
      reasons of delay were waiting for hospital admission and re-bronchoscopy. In the
      urban population, the most common reasons for delay were waiting for
      hospitalization and CT procedure. CONCLUSIONS: The results of the presented
      research allowed the following conclusions to be drawn: between the two assessed
      groups there were no differences in the length of the time of delay; 2) delays in
      diagnosis and treatment were too long for the patients and could affect the
      severity of the disease and final prognosis; 3) there is a need for
      intensification of information campaigns on lung cancer in order to reduce the
      delays dependent on patients, and to improve the cooperation of family doctors,
      pulmonologists, thoracic surgeons and oncologists.

PMID- 23540216
TI  - The efficacy of cognitive rehabilitation with RehaCom programme in schizophrenia
      patients. The role of selected genetic polymorphisms in successful cognitive
      rehabilitation.
AB  - INTRODUCTION: Schizophrenic patients present cognitive dysfunctions which are
      regarded to be one of endophenotypical markers predisposing to schizophrenia.
      Currently, schizophrenia can be treated as a neurodegenerative and
      neurodeveloping disease with genetic background. OBJECTIVE: Assessment of the
      possible positive effect of neuropsychological rehabilitation in schizophrenia,
      in patients presenting cognitive dysfunctions. An additional aim was to verify
      the hypothesis that some genetic polymorphisms can be a prognostic factor for
      success in neuropsychological rehabilitation. MATERIAL AND METHODS: 41
      participants and 40 control subjects were randomly selected. Both groups had the
      diagnosis of paranoid schizophrenia. Cognitive functions were checked with the
      Wisconsin Card Sorting Test, Trail Making Test, and Stroop Test at the beginning
      and end of the experiment. In the research group, each patient trained with the
      rehabilitation programme RehaCom, whereas the control group did not receive such
      training. Genes COMT rs4680 and BDNF rs6265 were analysed in the genetic part of
      study. RESULTS: RehaCom procedures appear to be useful in the neuropsychological
      rehabilitation of cognitive dysfunctions in patients diagnosed with
      schizophrenia. The research group showed a moderate improvement in the training
      programmes. Analysis of parameters obtained in the neuropsychological tests
      showed a slight improvement in both groups. At the present time, analysis of the
      polymorphisms of genes cannot be treated as a prognostic factor for the success
      of neuropsychological rehabilitation because statistical analyses showed few
      dependences with little statistical significance. CONCLUSIONS: Cognitive
      rehabilitation produces moderate improvement in cognitive functioning.

PMID- 23540217
TI  - Nicotinism and quality of embryos obtained in in-vitro fertilization programmes.
AB  - INTRODUCTION: According to the World Health Organization, infertility is defined
      as the inability to conceive following 12 months of regular unprotected sexual
      intercourse. Cigarette smoking, alcohol and drugs are the main stimulants
      exerting a negative effect on the male and female reproductive organs. OBJECTIVE:
      The objective of the study was analysis of the effect of cigarette smoking by the
      women examined and their partners on the quality of embryos obtained in in vitro
      fertilization programmes. MATERIAL AND METHODS: The study covered 54 women
      treated due to infertility. The database and statistical analyses were performed
      by means of computer software STATISTICA 7.1 (StatSoft, Poland). RESULTS: The
      study showed that among 100% of the women examined, 24.07% smoked cigarettes. No
      statistically significant difference was observed between cigarette smoking by
      the women in the study (p=0.42), and the number of cigarettes smoked daily
      (p=0.52) and the total duration of smoking expressed in years (p=0.56). In
      addition, the study showed that 33.33% of respondents were exposed to passive
      nicotinism, while 66.67% were not exposed to passive smoking. In the group of
      women exposed to passive smoking, Class A embryos constituted 11.11%, Class B
      embryos - 83.38%, whereas Class C embryos - only 5.56%. A statistically
      significant relationship was noted between classes of embryos and exposure to
      passive nicotinism (p=0.03). Passive smoking results in the development of
      embryos of poorer quality. A significantly higher number of Class 2 embryos were
      produced from oocytes of women exposed to the effect of cigarette smoke, compared
      to Class 1. Among women at reproductive age, an active campaign should be carried
      out against nicotinism on behalf of their fertility and future maternity.

PMID- 23540218
TI  - Incidence of abnormalities in temporomandibular joints in a population of 1,100
      urban and rural patients lacking teeth and other parafunctions in 2003-2008. An
      international problem.
AB  - INTRODUCTION AND OBJECTIVE: A hectic lifestyle and everyday stress are direct
      causes of parafunctions. The objective of the presented study was to examine the
      relation of sleep disorders, distant pain symptoms, symptoms of pathological
      tooth wear in rural and urban patients with parafunctions. MATERIALS AND METHODS:
      The patient group consisted of 836 women and 274 men aged 9-82, and divided into
      groups taking into account the following criteria: number of patients in certain
      age groups, number of women and men, place of residence, presence of missing
      teeth problem, presence of occlusal and non-occlusal parafunctions, symptoms of
      tooth wear, distant pain symptoms, and sleep disorders. RESULTS: 354 (31.89%) of
      the patients came from the rural environment. Distant pain symptoms were more
      frequent in patients performing parafunctions than in those who did not perform
      parafunctions (n = 1110, RR = 1.10, CI = from 1.04 to 1.16). Sleep disorders were
      more frequent in patients performing parafunctions than in those who do not
      perform parafunctions (n = 1110, RR = 1.06, CI = from 1.00 to 1.12). Symptoms of
      pathological tooth wear were more frequent in patients performing parafunctions
      than in those who did not perform parafunctions (n = 1110, RR = 1.08, CI = from
      1.02 to 1.13). CONCLUSIONS: It is extremely important (as it is international
      problem) to introduce prophylactic care to prevent the occurrence of
      parafunctional activity in patients from the rural environment. Parafunctions,
      therefore, should be taken into account in the diagnosing procedure of such
      disorders and pathological symptoms as pathological tooth wear, sleep disorders,
      cervicalgia, neck myalgia, shoulder girdle myalgia, and dorsalgia.

PMID- 23540219
TI  - Injuries due to human and animal aggression in humans.
AB  - INTRODUCTION: People breed animals, professionally take care of them, and work
      with them. To live with animals, however, it is necessary to know their behaviour
      and habits, as well as fears. Ignorance of this knowledge may lead to tragedy for
      the victim (a person), as well as for the beast (animal). Then, nobody cares
      whether the animal behaved itself or not in accordance with its nature.
      OBJECTIVE: The aim of the presented study is to compare the rate of animal
      aggression in relation to cases of documented aggression towards humans. The
      victims were investigated according to the age, gender and types of injuries
      caused by animal bites. MATERIAL AND METHODS: The protocols of autopsies (2,218)
      and medical-legal examinations (4,569) performed from 2004-2009 in the Department
      of Forensic Sciences in Poznan were analyzed. The selected data was studied using
      Microsoft Office Excel 2007 for Windows. RESULTS: Analysis revealed the presence
      of animal bite injuries in less than 1% of the deceased victims of aggression.
      The number of individuals who died as a result of animal bites varied from 1-4 a
      year, and in all cases these were postmortem injuries. Analysis of injuries among
      surviving victims of aggression showed animal bite injuries were present in 41
      out of 4,569 victims, almost equally among males and females. Moreover, in 25
      victims the bite injuries recognized as human were found. The majority of animal
      bites occurred in adults. The medium injuries were the most frequent in the
      animal bite victims. CONCLUSIONS: Animal aggression is a marginal problem
      considering all cases of aggression towards humans. In contrast to the aggression
      of humans towards other humans, this is a very rare cause of human death or even
      major injury.

PMID- 23540220
TI  - Determinant factors of health in rural women in their perimenopausal period.
AB  - The environment and lifestyle are known to exert an essential influence on the
      health of rural women in their perimenopausal period. OBJECTIVE: To assess the
      determinant factors of health in rural women in their perimenopausal period.
      MATERIAL AND METHODS: The study was carried out in 150 patients of the
      Gynecological Clinic of the Independent Public Heath Care Team (IPHCT) in
      Tomaszow Lubelski, southestern Poland, between 1 August 2010 - 30 April 2011. The
      women, aged 40-60 years, lived in a rural environment or villages. The study used
      a Menopause Health Questionnaire (MHQ) and Menopause Symptom Scale (MSS).
      Statistical analysis was based on Chi-Square Test, as well as U Mann-Whitney
      test, with a pertinence level of p<0.05. Data basis and statistics were collected
      using computer software STATISTICA 9.0 (StatSoft, Poland). RESULTS: More than a
      half of the investigated patients lived in the country (60.00%), with the
      remainder coming from villages (40.00%). About two-thirds of the patients
      (66.00%) had completed college education, and the majority stated that their
      financial situation was bad (30.00%), or average (32.00%). Only every fifth woman
      (19.33%) regularly had a gynecological check-up each year. Signs of anxiety or a
      depressive mood appeared to depend essentially (respectively: p = 0.000; p =
      0.02) on the professional status of the women. Only every fifth woman (20.7%)
      showed an appropriate weight. Just over a half of the rural women (50.67%)
      declared having a job. CONCLUSIONS: The professional status of rural women has a
      notable influence on their general well-being in the menopausal period. The
      majority of rural women hardly took care of their health or well-being. Worse
      (depressive) mood, irritability, frequent signs of anxiety, palpitation, heat
      strokes, and sexual disorders become important problems faced by women in the
      menopausal period.

PMID- 23540221
TI  - Urban vs. rural patients. Differences in stage and overall survival among
      patients treated surgically for lung cancer.
AB  - INTRODUCTION: Besides the undoubted influence of risk factors on morbidity and
      survival time, there are also other environmental factors, such as awareness of
      the prevalence of risk factors and the availability of modern diagnosis and
      treatment methods. OBJECTIVE: To evaluate differences in lung cancer 5-year
      overall survival rates between urban and rural patients hospitalized in the
      Department of Thoracic Surgery of the Medical University in Lublin, Poland, and
      possible influence of several risk factors on these rates. MATERIALS AND METHODS:
      The analysis was based on 125 lung cancer patients who underwent surgical
      procedures in years 2006-2007 and who agreed to take part in the survey. The
      study aimed at recognition of the health situation and selected demographic
      traits of people who had been treated surgically for lung cancer. The differences
      were evaluated between rural and urban inhabitants in gender, age, lung function,
      smoking habits, exposure to risk factors at work, family history of cancer,
      staging of the disease, histological type of cancer, post-surgical treatment, and
      their possible influence on overall survival. RESULTS: The results showed that
      the only noted differences between urban and rural population were in tobacco
      smoking and lung function. Survival rates were very similar and did not differ
      from the European average. CONCLUSIONS: The assumption that Polish rural patients
      are presenting with later cancer stages at the time of diagnosis, and have worse
      chances for survival, has become invalid in modern times.

PMID- 23540222
TI  - Determination and comparison of microbial loads in atmospheres of two hospitals
      in Izmir, Turkey.
AB  - INTRODUCTION AND OBJECTIVES: Nosocomial infections, also known as hospital
      acquired infections, has become one of the most important health problems in
      health care units worldwide. The presented study aims to determine the average
      amount of microorganism loads and to show that the atmospheres of the two
      hospitals can be a potential source regarding nosocomial infections. The effect
      of surface and floor disinfection processes in the two hospitals and the
      antibiotic susceptibility of the bacterial isolates were also evaluated.
      MATERIALS AND METHODS: Microorganisms were isolated from air samples collected
      from different areas (patient wards, corridors, operating theatres and
      postoperative units) of the two hospitals in Izmir. Sampling was conducted
      between December 2006 - March 2007. RESULTS: During the 3-month sampling period,
      the average number of live microorganisms in the air samples collected from
      second-class environments in the hospital 1 and the hospital 2 was found to be
      224.44 and 536.66 cfu/m(3) , respectively. The average number of microorganisms
      in hospital 2 collected before the disinfection process was higher than those
      after the disinfection process. However, because of the closure of the air
      conditioning system and the hepa filters after the disinfection process, this was
      reversed in hospital 1. In total, 54 and 42 isolates were obtained from hospital
      1 and hospital 2, respectively. 49 isolates from hospital 1 and 35 isolates from
      hospital 2 were identified as Staphylacoccus sp. The remaining isolates were
      identified as Aerococcus sp. and Enterococcus sp. Pseudomonas sp. was not
      determined in the air samples of the two hospitals. CONCLUSIONS: It was detected
      that the microbial loads in the atmospheres of the two hospitals studied varied
      greatly depending on the number of people in the environment. As the results
      indicate, the total number of microorganisms in the atmospheres of operating
      theatres in both hospitals does not pose a threat according to the Air Microbe
      Index.

PMID- 23540223
TI  - Level of magnesium in patients with depression treated with lithium -- pilotage
      research.
AB  - INTRODUCTION: Depression is a major public health problem. Magnesium (Mg(2+)) is
      involved in many metabolic processes as an activator of over 300 different
      enzymes. For the last 60 years lithium (Li(+)) compounds have been used in
      psychiatry. Li(+) salts are regarded as the first choice medicine in the
      treatment of affective disorders and are also applied as an adjuvant intensifying
      the therapy in drug-resistant depression patients. OBJECTIVE: The objective of
      the study was an analysis of the relationship between the levels of magnesium,
      lithium, and education and place of residence of patients hospitalized due to
      depression. MATERIAL AND METHODS: Patients with bipolar affective disorders
      undergoing lithium therapy during their stay in the Department of Psychiatry at
      the Medical University in Lublin were examined. Patients were divided into three
      groups according to education level and were also analyzed according to place of
      residence. RESULTS: In the group of patients in the study, a significantly lower
      level of magnesium was found (p=0.02) in blood plasma of patients with secondary
      education level, compared to those who had elementary education. There was also a
      significantly higher level of magnesium (p=0.01) in blood plasma of patients who
      lived in urban areas, compared to rural inhabitants. No statistically significant
      differences were noted between lithium level in plasma, and the patients' place
      of residence (p=0.34). CONCLUSION: Significantly higher plasma magnesium levels
      were observed among city than village inhabitants, there was also a relationship
      between type of education and magnesium level in blood plasma of the patients in
      the study. Further studies including larger groups of patients should be
      performed to enable a final conclusion.

PMID- 23540224
TI  - Glycated hemoglobin, diabetes treatment and cancer risk in type 2 diabetes. A
      case-control study.
AB  - INTRODUCTION: Type 2 diabetes is associated with an increased risk of some types
      of cancer. Diabetes treatment may also modify cancer risk. OBJECTIVE: The aim of
      this retrospective, case-control study was to assess whether HbA1c level and use
      of anti-diabetic drugs are associated with cancer development in a diabetic
      population. MATERIALS AND METHODS: The case group consisted of 53 patients who
      developed cancer after diagnosis of diabetes. They were compared with 53 diabetic
      subjects without cancer, strictly matched to a case group by age and gender. In
      both groups - apart from HbA1c and diabetes treatment - demographic data, smoking
      habits, comorbidities, BMI, diabetes duration, use of aspirin, antihypertensive
      and hypolipemic drugs were also analyzed. RESULTS: Patients with cancer had a
      significantly higher mean HbA1c value compared with the control group, 7.83+/
      1.26% vs. 7.30+/-1.08%, respectively (p=0.022). The distribution of patients in
      four HbA1c categories (<7.0, 7.0-7.9, 8.0-8.9 and >=9.0%) was significantly
      different between the two groups (p=0.031). The probability of cancer was higher
      among patients with HbA1c value >=8.0 % OR 3.160 (95% CI 1.342-7.440), p=0.013,
      and lower among patients using metformin, OR 0.228 (95% CI 0.083-0.633), p=0.006.
      The number of insulin users, insulin dose, duration of insulin treatment, and use
      of other anti-diabetic drugs were not significantly different between the two
      groups. Also, no significant differences were found between the two groups
      regarding other variables. CONCLUSIONS: The presented case-control study
      indicated an important role of metabolic control and confirmed the protective
      role of metformin in reducing cancer risk among patients with type 2 diabetes.
      Contrary to other studies, insulin use was not associated with a higher risk of
      cancer. Other anti-diabetic drugs appeared to have a neutral impact on cancer
      development.

PMID- 23540225
TI  - Westernization of dietary patterns among young Japanese and Polish females -- a
      comparison study.
AB  - INTRODUCTION AND OBJECTIVE: Nowadays, the process of the westernization of eating
      habits is perceived to be one of the main causes of epidemics of civilization
      diseases, such as metabolic syndrome. The aim of the study was to assess the
      westernization of eating habits among 100 Japanese (aged 18-23 years) and 111
      Polish female students (aged 19-25 years) of nutrition science related faculties.
      MATERIALS AND METHODS: Food-frequency questionnaires were used to assess a
      dietary pattern during the four seasons of a one-year investigation. Data
      obtained in each season was pooled. The frequency of consumption of different
      foods (servings/week) between the two countries was compared and characterization
      of the dietary patterns of both studied populations was analyzed by factor
      analysis. RESULTS: When food consumption between the two countries was compared,
      apart from total meat and meat products and high-energy drink intake, significant
      differences were observed in all foods and food groups. Three dietary patterns
      were identified in both groups. Among Japanese participants, the first pattern
      was 'traditional Japanese', the second 'sweets and beverages', and the third
      'Western', explaining 9.0%, 8.5% and 6.4% of the total variance, respectively.
      Among Polish participants, the first pattern was 'prudent', the second 'Western',
      and the third 'sweets and alcoholic beverages', explaining 8.2%, 7.7%, 6.4% of
      the total variance, respectively. Although the 'Western' dietary pattern was
      found in both groups, there were some differences in the remaining dietary
      patterns between the two countries. CONCLUSIONS: In the Japanese participants,
      significant cultural influences on habitual food intake could still be observed,
      and the extent of diet westernization seems to be smaller compared to the Polish
      participants.

PMID- 23540226
TI  - No associations between rs2030712 and rs7456421 single nucleotide polymorphisms
      of HIPK2 gene and prevalence of chronic kidney disease. Results of a family-based
      study.
AB  - INTRODUCTION: Different pathological processes can deteriorate kidney function
      and cause ireversible degeneration of its structure; however, an optimal way to
      inhibit or slow down progression of renal damage is unforunately not available.
      In the light of promissing data concerning homeodomain-interacting protein kinase
      2 (HIPK2) upregulation in damaged kidneys animal model, and increased levels of
      this protein in patients with various kidney diseases, the influence of rs7456421
      and rs 2030712 single nucleotide polimorphisms of HIPK2 gene on chronic kidney
      disease incidence and progression was studied. MATERIAL AND METHODS: In 109
      family 'trios', consisting of an affected child with CKD (48 females and 61
      males, mean age 15.5 +/-6.45 years) and both his/her parents, using Transmission
      Disequilibrium Test allele was used for the transfer of afore-mentioned SNPs from
      biological parents to their affected offspring. RESULTS: No statistical
      significance of allele transfer was found, which means that there were no
      associations between rs7456421 and rs 2030712 SNPs of HIPK2 gene and the
      incidence of renal dysfunction. Multiple stepwise regression showed a history of
      chronic glomerulonephritis (OR=17.3), chronic interstitial nephritis without
      urinary tract defect (OR=4.4), and CT genotype of rs 2030712 SNP (OR=2.6) as
      determinant of a more rapid progression of renal dysfunction, in contrast to the
      protective action of body mass index (OR=0.86). CONCLUSIONS: On the basis of TDT
      results, the influence of rs7456421 and rs 2030712 SNPs of HIPK2 gene on
      prevalence of chronic kidney disease was not identified. Further studies are
      needed to ascertain the tight relationships of HIPK2 gene polymorphisms with CKD
      of different etiologies.

PMID- 23540227
TI  - Medical and psychosocial factors conditioning development of stress urinary
      incontinence (SUI).
AB  - INTRODUCTION: Stress urinary incontinence (SUI) is the most frequent type of
      urinary incontinence among adult women. OBJECTIVE: The objective of the study was
      evaluation of the effect of environmental, systemic and obstetrical factors on
      the development of stress urinary incontinence, and diagnosing and determination
      of areas in which changes could be made. MATERIAL AND METHOD: The study covered
      313 females aged 30-75 living in the Lublin Region. The respondents were divided
      into two groups according to the clinical diagnosis, occurrence of symptoms of
      SUI or lack thereof: Group I - women with SUI symptoms (119), Group II - women
      without SUI (194). A diagnostic survey was conducted with the use of a self
      designed research instrument based on the Gaudenz questionnaire, data from
      relevant literature and the 'competent judges' test. The following statistical
      tests were used to compare two structure indicators (fraction, frequency); chi
      square test and t-Student test. Statistical analysis was performed by means of
      STATISTICA 9 (StatSoft) software. RESULTS AND CONCLUSIONS: Statistically
      significant differences were found between the group of patients with SUI and the
      control group, with respect to the number of deliveries and their duration. The
      study showed that there is a statistically higher probability of the development
      of SUI in the case of surgical delivery, or natural childbirth of a baby with a
      birth weight of 4000 g or more. The study showed that hard physical work and past
      gynaecological surgeries are risk factors of urinary incontinence. Barriers of a
      psychosocial nature were also found (feeling of shame and embarrassment
      accompanying disclosure of the SUI), which minimized the respondents'
      participation in urinary incontinence prophylactic actions.

PMID- 23540228
TI  - Type III Polyglandular Autoimmune Syndromes in children with type 1 diabetes
      mellitus.
AB  - INTRODUCTION: Type III Polyglandular Autoimmune Syndrome (PAS III) is composed of
      autoimmune thyroid diseases associated with endocrinopathy other than adrenal
      insufficiency. This syndrome is associated with organ-specific and organ
      nonspecific or systemic autoimmune diseases. The frequency of PAS syndromes in
      diabetic children is unknown. OBJECTIVES: The aim of the study was to evaluate
      the incidence of PAS III in children with diabetes mellitus type 1. PATIENTS AND
      METHODS: The study consisted of 461 patients with diabetes mellitus type 1(T1DM),
      who were 1-19 years of age. TSH, free thyroxin, TPO autoantibodies, and
      thyroglobulin autoantibodies were determined annually. Autoimmune Hashimoto's
      thyroiditis was diagnosed in children with positive tests for TPO Ab and Tg Ab
      and thyroid parenchymal hypogenicity in the ultrasound investigation. Elevated
      TSI antibodies were used to diagnose Graves' disease. Additionally, Anti
      Endomysial Antibodies IgA class were determined every year as screening for
      celiac disease. During clinical control, other autoimmune diseases were
      diagnosed. Adrenal function was examined by the diurnal rhythm of cortisol.
      RESULTS: PAS III was diagnosed in 14.5% children: PAS IIIA (T1DM and autoimmune
      thyroiditis) was recognized in 11.1 % and PAS III C (T1DM and other autoimmune
      disorders: celiac disease, and JIA, psoriasis and vitiligo) in 3.5% children. PAS
      IIIA was more prevalent in girls than in boys - 78.4% versus 21.6% (p<0.05). PAS
      III was observed between 1-5 years of life in 66.6% children; the frequency
      decreased in consecutive years and successively increased in the adolescence
      period to 22.7%. CONCLUSIONS: PAS III occurs in 14.5% of children with DM type1
      and the incidence is positively correlated with patients' age and female gender.
      Children with PAS III should be carefully monitored as a group at risk for the
      development of other autoimmune diseases.

PMID- 23540229
TI  - Effect of menopausal hormone therapy on the levels of magnesium, zinc, lead and
      cadmium in post-menopausal women.
AB  - INTRODUCTION AND OBJECTIVE: The level of trace elements is extremely important
      for the maintenance of normal functioning of the human body. The risk of
      disturbance of their balance increases especially dynamically during the period
      of menopause. The objective of the study was the effect of MHT on the levels of
      bioelements (Mg and Zn) in blood plasma, and toxic metals (Pb and Cd) in the
      whole blood in postmenopausal women. MATERIALS AND METHODS: The study covered 323
      women at postmenopausal age from the population of the West Pomeranian Region, in
      whom the levels of Mg, Zn, Pb and Cd were determined. The women were divided into
      two groups: study and control. The study group were 152 women who used menopausal
      hormone therapy (MHT). The control group were 171 women who did not use MHT, and
      had had their final menstrual period at least one year prior to inclusion in the
      study. The mean age of the women examined was 56+/-5. RESULTS: Significantly
      higher levels of the bioelements Mg, Zn were observed in women who used MHT,
      compared to the control group (p<0.05). The concentration of Pb in whole blood
      was significantly lower in the study than the control group: 16.09+/-7.33 ug/l
      and 20.18+/-9.01 ug/l, respectively. An elevated level of Cd in whole blood was
      found in both groups of women: 0.9+/-1.03 ug/l and 0.8+/-1.1 ug/l, respectively.
      It was noted that women who used MHT more frequently declared the presence of
      climacteric symptoms (p<0.05). CONCLUSIONS: 1) Higher levels of Mg and Zn were
      found in blood plasma of women who used MHT. 2) The mean concentration of Cd in
      the blood of women in both groups was similar. 3) In women who use MHT the level
      of Pb in whole blood was lower, compared to the rest of the women.

PMID- 23540230
TI  - Clinical factors affecting the perception of hypoglycemia in type 1 diabetes
      patients treated with personal insulin pumps.
AB  - INTRODUCTION AND OBJECTIVE: The ability to perceive the symptoms of hypoglycemia
      during the early decrease in plasma glucose concentration may be critical for the
      safety of T1DM patients treated with intensive insulin therapy, including those
      treated with continuous subcutaneous insulin infusion (CSII). In the presented
      observational study an attempt was made to asses clinical factors that might
      affect subjective awareness of hypoglycemia in CSII-treated T1DM patients, with
      special attention to factors specific for this mode of treatment. MATERIALS AND
      METHODS: For the purpose of the study, data of 110 CSII-treated T1DM patients
      were collected (78 females and 32 males). The records were analyzed from glucose
      meters (200-300 measurements/download, depending on meter type) and insulin pumps
      (total insulin dose, basal/bolus ratio, number of boluses/day, bolus calculator
      and dual wave/square bolus usage, continuous glucose monitoring data) from the
      last 3 years. RESULTS: It was found that the level of subjective hypoglycemia
      perception inversely correlated with the number of hypoglycemic episodes per 100
      measurements, age, duration of diabetes, time on insulin pump, and positively
      correlated with mean glycemia (n = 98; r = 0.22; p = 0.0286). With respect to
      CSII-related factors, hypoglycemia perception inversely correlated with the
      percentage of basal insulin (n = 106; r = -0.20; p = 0.0354). In stepwise
      regression analysis, independent predictors for impaired hypoglycemia perception
      were: age beta = -0.29 (p = 0.023), duration of diabetes beta = -0.24 (p = 0.029)
      and number of the hypoglycemia episodes for 100 measurements beta = -0.33 (p =
      0.0005). CONCLUSIONS: Risk factors for impaired hypoglycemia perception in CSII
      treated patients include those identified previously for the general population
      of T1DM individuals. In addition, the presented results suggest that a higher
      basal/bolus ratio may lead to impairment of the ability to perceive early
      symptoms of hypoglycemia.

PMID- 23540231
TI  - Should a doctor stop rendering medical services? Principles of conduct towards
      patients attempting to commit suicide. Part 1 -- the Polish perspective.
AB  - INTRODUCTION: According to the general idea a doctor can start the medical
      management process in an adult and not legally incapacitated patient after the
      patient has given consent to initiate such a process. The patient's refusal makes
      rendering medical services impossible, irrespective of their scope and kind. It
      should be emphasized that such a refusal is respected if it is expressed fully,
      clearly and consciously. Cases in which such a refusal is expressed by an
      intoxicated suicidal patient, remaining under the influence of narcotics, drugs
      or medicaments which characterize with a similar activity should be particularly
      analysed. Although such a person is able to verbally declare his objection, his
      ability to process the information given by the doctor before initiating medical
      procedures is limited, or even non-existant. The refusal therefore cannot be
      regarded as reliable, which results in rendering medical services to the patient.
      MATERIALS AND METHODS: An analysis was made of Acts of Law and the opinions of
      the judiciar by comparing and excluding contradictory and incoherent elements.
      RESULTS: Despite the lack of clear regulations of a patient rejecting procedures
      aimed at saving the patient's life, or the prevention of serious health
      impairment or sustaining injury, it should be assumed that the objection
      expressed by the patient who does not demonstrate the ability to process the
      information provided by the doctor is not reliable, and the doctor is therefore
      still obliged to render medical services. External factors, such as consumption
      of alcohol, narcotics and drugs, which characterize with a similar activity
      impair perception and make the taking of a conscious decision impossible. Not
      providing medical help and introducing direct compulsion would mean neglecting
      provision of due diligence in the process of treatment and, as a consequence,
      placing the patient's health at risk, and suffering from negative implications
      for the patient's life and/or health in the future. CONCLUSIONS: Current
      provisions should directly regulate the negligence of respecting a refusal
      expressed 'unconsciously' by a patient who remains under the influence of
      alcohol, narcotics, drugs or medicaments which characterize with a similar
      activity. Moreover, apart from legal provisions, the law providers should
      consider introducing a direct compulsion in patients who are unable to make a
      conscious decision in the treatment process.

PMID- 23540232
TI  - Waiting time for treatment of women with breast cancer in Podlaskie Voivodeship
      (Poland) in view of place of residence. A population study.
AB  - INTRODUCTION: Treatment delay is a major problem of contemporary oncology.
      Knowing the time interval between diagnosis and initiation of treatment, together
      with monitoring this adverse prognostic factor, is an important element of the
      treatment planning process in the population and can contribute to the
      improvement of patients' curability. OBJECTIVE: To assess the waiting time for
      first treatment of women diagnosed with breast cancer in 2001-2002 in Podlaskie
      Voivodeship. MATERIALS AND METHODS: During 2001-2002, there were 709 cases of
      women with breast cancer who reported to the Voivodeship Cancer Registry in
      Bialystok. 659 women were diagnosed with a primary invasive breast tumour. A
      cohort of 499 women who were treated with a curative intent was selected from
      this group. The waiting time in the created cohort was calculated as the number
      of days between the date of the breast cancer diagnosis and date of the first
      treatment. RESULTS: The average time between the date of diagnosis and date of
      the first treatment was 38 days. The median was 14 days. 28.6% of patients from
      the selected cohort waited longer than 28 days. The treatment of rural women was
      initiated faster than the treatment of urban patients.

PMID- 23540233
TI  - Effect of an anti-tobacco programme of health education on changes in health
      behaviours among junior high school adolescents in Bialystok, Poland.
AB  - INTRODUCTION: School health education programmes are among the instruments for
      the prevention of tobacco smoking among children and adolescents. Knowledge
      obtained in evaluation studies of these programmes indicates the degree of their
      effectiveness and serves to improve their quality. OBJECTIVE: Recognition and
      evaluation of the effect of two-year anti-tobacco programme of health education
      on the changes in the level of knowledge, attitudes and behaviours of
      adolescents. MATERIALS AND METHOD: An intervention study was originated in May
      2007, and covered 859 first-year schoolchildren from eight public junior high
      schools in Bialystok in Poland, from among 3,318 schoolchildren attending 33
      schools. The sample was selected by means of two-stage stratified sampling with
      consideration of two groups: an intervention group covered with educational
      actions (417 schoolchildren), and a control group (442 schoolchildren), where
      anti-tobacco education was not carried out. Before the educational programme and
      after its completion an evaluation of knowledge, attitudes and behaviours of
      junior high school adolescents was performed with respect to nicotinism, based on
      a survey. The educational part consisted in conducting within 2 years, 4
      educational classes and 2 competitions concerning tobacco-related problems.
      RESULTS: After two years, in the group of adolescents covered by the educational
      programme a significant increase was observed - by 11.6% - in the percentage of
      schoolchildren who were familiar with the negative effects of tobacco smoking,
      and an increase by 4.4% of those who were convinced that smoking is harmful. With
      respect to adolescents' attitudes, the effect of the programme was noted in only
      one of six components analyzed. After completion of the two-year educational
      programme, both in the group covered by this programme and the control group, the
      percentage of smokers significantly increased (by 12.8% and 12.7%, respectively).
      CONCLUSIONS: It is necessary to evaluate the health education programme from the
      aspect of both the actual hard effects of the anti-nicotine programme (changes in
      behaviour), and indirect effects - soft (knowledge, skills) which are a basis for
      the potential verification of the programme in order to increase its
      effectiveness.

PMID- 23540234
TI  - Differences in the effects of anti-tobacco health education programme in the
      areas of knowledge, attitude and behaviour, with respect to nicotinism among boys
      and girls.
AB  - INTRODUCTION: Health education used for increasing the effectiveness of
      intervention actions should cover a number of factors which exert an effect on
      learning. OBJECTIVE: Recognition of the extent to which gender may determine the
      effects of an anti-tobacco health education programme. MATERIAL AND METHODS: The
      intervention study was undertaken in May 2007, and covered 859 first-year
      schoolchildren in Bialystok. The sample was selected by means of two-stage
      stratified sampling with consideration of two groups: an intervention group and a
      control group. RESULTS: In the group of girls, the 2-year educational programme
      resulted in an increase in knowledge concerning the negative effects of cigarette
      smoking by 21%, and being familiar with anti-tobacco actions and campaigns
      carried out in Poland by 24.5%. Among boys, an increase was observed only with
      respect to the knowledge of anti-tobacco actions and campaigns - by 10.7%.
      Considering the attitudes of girls after the completion of the programme, changes
      were noted with respect to three from among the six elements analyzed. However,
      among boys, after completion of the project, no changes were noted in any of the
      analyzed elements of attitude. In girls who participated in the anti-nicotine
      programme, the percentage of smokers did not increase, while an increase in this
      percentage was observed among girls of the control group and boys in both groups.
      CONCLUSIONS: Different effects of the 2-year anti-tobacco programme obtained in
      the area of knowledge, attitude and behaviour should constitute a premise for the
      modification of educational programmes from the aspect of the variety of methods,
      techniques and instruments which would be adequate for adolescents'
      predispositions resulting also from their gender.

PMID- 23540235
TI  - Influence of a vertical deviation of a 10-storey apartment building in Katowice,
      Poland, on selected mental functions of its occupants. A preliminary study.
AB  - INTRODUCTION AND OBJECTIVES: Coal exploitation technology could have affected the
      deformation of ground under a housing estate in the Upper Silesia agglomeration.
      The 10-storey apartment building began to deviate from the vertical. These
      factors affected the housing conditions of inhabitants in the block of flats.
      From 1991-2001, coal-mine surveyors monitored the vertical deviation. The
      inhabitants of the apartment building decided to put in a claim to their housing
      association which subsequently requested that the coal mine authorities repair
      the damages. The coal mine authorities initially refused to acknowledge
      inhabitants claim. MATERIALS AND METHODS: An interdisciplinary group of experts
      were engaged who examined the group of inhabitants. Generally accepted and
      evidence based psychological methods were selected and certified, and
      psychological equipment was used. RESULTS: Preliminary deductions showed a strict
      connection between psychical discomfort, negative stress and vertical deviation.
      Based on the experts' report, the housing association decided to sue the coal
      mine authorities who offered to settle the inhabitants' grievances out of court
      and to straighten the apartment building - an influenced decision. CONCLUSIONS:
      This report is one of the best documented examples of a health impact assessment
      conducted in the 1990, a long time before the legal and methodological basis of
      Health Impact Assessment (HIA) and Environmental Impact Assessment (EIA) began to
      be implemented in other European countries.

PMID- 23540236
TI  - Professional communication competences of nurses -- a review of current practice
      and educational problems.
AB  - BACKGROUND: A dissonance between high 'technical' professionalism of nurses and a
      relatively low level of patient satisfaction with received care is a phenomenon
      observed in many countries. METHOD: Theoretical concept and review of current
      published studies. DISCUSSION: Most reviewed studies show that a low level of
      patient satisfaction occurs in the case of an inadequate interpersonal
      communication between nurses and patients. Most studies indicate poor
      effectiveness of shaping communication competences of nurses based on standard
      education in the area of general psychology and communication knowledge, because
      this knowledge does not convert itself 'spontaneously' into communication
      competences during occupational activity. CONCLUSIONS: It is necessary to
      supplement educational programmes for nurses with practical courses in
      professional interpersonal communication. International experience exchange
      concerning the shaping of nurses' communication competences may be limited due to
      cultural, organizational and systems factors.

PMID- 23540237
TI  - Professional communication competences of physiotherapists -- practice and
      educational perspectives.
AB  - BACKGROUND: Dissonance between the high 'technical' competences of medical
      professionals, including physiotherapists, and the relatively low level of
      patient satisfaction with care received is a phenomenon observed in many
      countries. Many studies show that it occurs in the case of an inadequate
      interpersonal communication between medical professionals and patients.
      OBJECTIVES: The primary goal of the presented research was evaluation of the
      level (study of the state) of communication competences of physiotherapists, and
      determination of the factors on which this level depends. An additional goal was
      analysis of the needs and educational possibilities within the existing models of
      education in the area of interpersonal communication provided by higher medical
      education institutions. DESIGN, SETTING AND PARTICIPANTS: The self-designed
      questionnaire and adjective check list were subject to standardization from the
      aspect of reliability and validity. Information available on the websites of 20
      educational facilities in Poland were compared. The study group covered a total
      number of 115 respondents in the following subgroups: 1) occupationally-active
      physiotherapists who, as a rule, were not trained in interpersonal communication
      (35 respondents); students of physiotherapy covered by a standard educational
      programme (60 respondents); 3) students of physiotherapy who, in addition to a
      standard educational programme, attended extra courses in professional
      interpersonal communications (20 respondents). RESULTS: The results of studies
      indicate poor efficacy of shaping communication competences of physiotherapists
      based on education in the area of general psychology and general interpersonal
      communication. Communication competences acquired during undergraduate
      physiotherapy education are subject to regression during occupational activity.
      CONCLUSIONS: Methods of evaluating communication competences are useful in
      constructing group and individual programmes focused on specific communication
      competences, rather than on general communication skills.

PMID- 23540238
TI  - Socio-demographical and psychosocial determinants of anxiety symptoms in a
      population of pregnant women in the regions of central and eastern Poland.
AB  - INTRODUCTION AND OBJECTIVE: Until recently, depression and anxiety during
      pregnancy were a neglected medical problem. The purpose of this study was to
      determine the prevalence of symptoms of anxiety and depression during pregnancy
      and identification of the socio-demographic and psychosocial factors. MATERIAL
      AND METHODS: The study was prospective and longitudinal, and the research group
      consisted of 314 adult pregnant women. To assess the prevalence of anxiety
      symptoms and depression, the Hospital Anxiety and Depression Scale (HADS) was
      applied. To assess the psychosocial variables the Rosenberg Self-Assessment
      Scale, Marital Communication Questionnaire and the Berlin Social Support Scale
      and authors' Socio-demographical questionnaire were used. To assess the normal
      distribution the Shapiro-Wilk test was used. For non-parametric tests the Mann
      Whitney U test and Kruskal Wallis ANOVA were used due to the distribution of the
      variables tested against the intergroup comparisons that deviate from the normal
      distribution. RESULTS AND CONCLUSIONS: Co-existence of anxiety and depression in
      different trimesters amounted relatively to 12.7% in the first trimester, 10.8%
      in the second trimester and 12.4% in the third trimester of pregnancy. Symptoms
      of anxiety were often experienced by unmarried women, non-working women, and
      those respondents who estimated their housing and financial situation as being
      worse. Those most susceptible to depressive symptoms were tested women with
      primary education and those who assessed as worse their financial and housing
      situation. Higher self-esteem, good communication in a relationship, satisfying
      social support was associated with a lower incidence of anxiety symptoms during
      pregnancy. Higher self-esteem, good communication in a relationship, and
      satisfying social support was associated with a lower incidence of anxiety
      symptoms during pregnancy.

PMID- 23540242
TI  - Use of isotope ratio mass spectrometry to differentiate between endogenous
      steroids and synthetic homologues in cattle: a review.
AB  - Although substantial technical advances have been achieved during the past
      decades to extend and facilitate the analysis of growth promoters in cattle, the
      detection of abuse of synthetic analogs of naturally occurring hormones has
      remained a challenging issue. When it became clear that the exogenous origin of
      steroid hormones could be traced based on the (13)C/(12)C isotope ratio of the
      substances, GC/C/IRMS has been successfully implemented to this aim since the end
      of the past century. However, due to the costly character of the instrumental
      setup, the susceptibility of the equipment to errors and the complex and time
      consuming sample preparation, this method is up until now only applied by a
      limited number of laboratories. In this review, the general principles as well as
      the practical application of GC/C/IRMS to differentiate between endogenous
      steroids and exogenously synthesized homologous compounds in cattle will be
      discussed in detail, and will be placed next to other existing and to be
      developed methods based on isotope ratio mass spectrometry. Finally, the link
      will be made with the field of sports doping, where GC/C/IRMS has been
      established within the World Anti-Doping Agency (WADA) approved methods as the
      official technique to differentiate between exogenous and endogenous steroids
      over the past few years.

PMID- 23540243
TI  - Multivariate curve resolution-particle swarm optimization: a high-throughput
      approach to exploit pure information from multi-component hyphenated
      chromatographic signals.
AB  - Multivariate curve resolution-particle swarm optimization (MCR-PSO) algorithm is
      proposed to exploit pure chromatographic and spectroscopic information from multi
      component hyphenated chromatographic signals. This new MCR method is based on
      rotation of mathematically unique PCA solutions into the chemically meaningful
      MCR solutions. To obtain a proper rotation matrix, an objective function based on
      non-fulfillment of constraints is defined and is optimized using particle swarm
      optimization (PSO) algorithm. Initial values of rotation matrix are calculated
      using local rank analysis and heuristic evolving latent projection (HELP) method.
      The ability of MCR-PSO in resolving the chromatographic data is evaluated using
      simulated gas chromatography-mass spectrometry (GC-MS) and high-performance
      liquid chromatography-diode array detection (HPLC-DAD) data. To present a
      comprehensive study, different number of components and various levels of noise
      under proper constraints of non-negativity, unimodality and spectral
      normalization are considered. Calculation of the extent of rotational ambiguity
      in MCR solutions for different chromatographic systems using MCR-BANDS method
      showed that MCR-PSO solutions are always in the range of feasible solutions like
      true solutions. In addition, the performance of MCR-PSO is compared with other
      popular MCR methods of multivariate curve resolution-objective function
      minimization (MCR-FMIN) and multivariate curve resolution-alternating least
      squares (MCR-ALS). The results showed that MCR-PSO solutions are rather similar
      or better (in some cases) than other MCR methods in terms of statistical
      parameters. Finally MCR-PSO is successfully applied in the resolution of real GC
      MS data. It should be pointed out that in addition to multivariate resolution of
      hyphenated chromatographic signals, MCR-PSO algorithm can be straightforwardly
      applied to other types of separation, spectroscopic and electrochemical data.

PMID- 23540244
TI  - Aptamer based strategy for cytosensing and evaluation of HER-3 on the surface of
      MCF-7 cells by using the signal amplification of nucleic acid-functionalized
      nanocrystals.
AB  - The electrochemical detection of cell lines of MCF-7 (human breast cancer) has
      been reported, using magnetic beads for the separation tool and high-affinity DNA
      aptamers for signal recognition. The high specificity was obtained by using the
      magnetic beads and aptamers, and the good sensitivity was realized with the
      signal amplification of DNA capped CdS or PbS nanocrystals. The ASV (anodic
      stripping voltammetry) technology was employed for the detection of cadmic cation
      and lead ions, for electrochemical assay of the amount of the target cells and
      biomarkers on the membrane of target cells, respectively. This electrochemical
      method could respond to as low as 100 cells mL(-1) of cancer cells with a linear
      calibration range from 1.0*10(2) to 1.0*10(6) cells mL(-1), showing very high
      sensitivity. Moreover, the amounts of HER-3 which were overexpressed on MCF-7
      cells were calculated correspond to be 3.56*10(4) anti-HER-3 antibody molecules.
      In addition, the assay was able to differentiate between different types of
      target and control cells based on the aptamers and magnetic beads used in the
      assay, indicating the wide applicability of the assay for early and accurate
      diagnose of cancers.

PMID- 23540245
TI  - Cork as a new (green) coating for solid-phase microextraction: determination of
      polycyclic aromatic hydrocarbons in water samples by gas chromatography-mass
      spectrometry.
AB  - A new fiber for solid-phase microextraction (SPME) was prepared employing cork as
      a coating. The morphology and composition of the cork fiber was evaluated by
      scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy
      (FTIR), respectively. The proposed fiber was used for the determination of
      polycyclic aromatic hydrocarbons (PAHs) in river water samples by gas
      chromatography-selected ion monitoring-mass spectrometry (GC-SIM-MS). A central
      composite design was used for optimization of the variables involved in the
      extraction of PAHs from water samples. The optimal extraction conditions were
      extraction time and temperature of 60 min and 80 degrees C, respectively. The
      detection and quantification limits were 0.03 and 0.1 MUg L(-1), respectively.
      The recovery values were between 70.2 and 103.2% and the RSD was <=15.7 (n=3).
      The linear range was 0.1-10 MUg L(-1) with r>=0.96 and the fiber-to-fiber
      reproducibility showed RSD<=18.6% (n=5). The efficiency of the cork fiber was
      compared with commercially available fibers and good results were achieved,
      demonstrating the applicability and great potential of cork as a coating for
      SPME.

PMID- 23540246
TI  - Peptides trapping cocaine: docking simulation and experimental screening by solid
      phase extraction followed by liquid chromatography mass spectrometry in plasma
      samples.
AB  - Two different hexapeptides were computationally designed and tested as selective
      SPE sorbent for cocaine. The amino acid residues used for designing the two
      hexapeptides, tested in SPE experiments, were, according to chemical function and
      interatomic distances, the most (QHWWDW) and the lowest (ESSIDH) preserved
      sequences in 4 proteins binding cocaine. The hexapeptide-cocaine complex was
      docked with different scoring functions combinations and resulting binding scores
      were compared with the SPE results. The extraction procedure for SPE was
      optimized considering volume loading, pH effect, and human plasma matrix
      interferences. Cocaine was loaded onto the modified resin cartridge at 10 ng mL(
      1) and the peptide QHWWDW was found to have the highest recovery with the best
      retention at pH 7.5, in agreement with docking simulation. Retention experiments
      were carried out also on cocaine metabolites nor-cocaine, benzoylecgonine and
      ecgonine methyl ester. Except for nor-cocaine the retention of metabolites on
      resin modified with peptide QHWWDW decreased drastically confirming the peptide
      selectivity, and validating the simulation data. Compared to standard solutions,
      only a slight decrease in cocaine recovery was observed loading human plasma
      samples after a partial protein precipitation.

PMID- 23540247
TI  - Correlation of precursor and product ions in single-stage high resolution mass
      spectrometry. A tool for detecting diagnostic ions and improving the precursor
      elemental composition elucidation.
AB  - Monitoring of common diagnostic fragments is essential for recognizing molecules
      which are members of a particular compound class. Up to now, unit resolving
      tandem quadrupole mass spectrometers, operating in the precursor ion scan mode,
      have been typically used to perform such analysis. By means of high-resolution
      mass spectrometry (HRMS) a much more sensitive and selective detection can be
      achieved. However, using a single-stage HRMS instrument, there is no unequivocal
      link to the corresponding precursor ion, since such instrumentation does not
      permit a previous precursor selection. Thus, to address this limitation, an in
      silico approach to locate precursor ions, based on diagnostic fragments, was
      developed. Implemented as an Excel macro, the algorithm rapidly assembles and
      surveys exact mass data to provide a list of feasible precursor candidates
      according to the correlation of the chromatographic peak shape profile and other
      additional filtering criteria (e.g. neutral losses and isotopes). The macro was
      tested with two families of veterinary drugs, sulfonamides and penicillins, which
      are known to yield diagnostic product ions when fragmented. Data sets obtained
      from different food matrices (fish and liver), both at high and low concentration
      of the target compounds, were investigated in order to evaluate the capabilities
      and limitations of the reported approach. Finally, other possible applications of
      this technique, such as the elucidation of elemental compositions based on
      product ions and corresponding neutral losses, were also presented and discussed.

PMID- 23540248
TI  - Absolute quantification of NAD(P)H:quinone oxidoreductase 1 in human tumor cell
      lines and tissues by liquid chromatography-mass spectrometry/mass spectrometry
      using both isotopic and non-isotopic internal standards.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) is a prognostic biomarker
      and a potential therapeutic target for various tumors. Therefore, it is of
      significance to develop a robust method for the absolute quantification of NQO1.
      This study aimed to develop and validate a LC-MS/MS based method and to test the
      appropriateness of using non-isotopic analog peptide as the internal standard
      (IS) by comparing with a stable isotope labeled (SIL) peptide. The
      chromatographic performance and mass spectra between the selected signature
      peptide of NQO1 and the non-isotopic peptide were observed to be very similar.
      The use of the two internal standards was validated appropriate for the absolute
      quantification of NQO1, as evidenced by satisfactory validation results over a
      concentration range of 1.62-162 fmol MUL(-1). This method has been successfully
      applied to the absolute quantification of NQO1 expression in various tumor cell
      lines and tissues. NQO1 expression in human tumor tissues is much higher than
      that in the neighboring normal tissues in both the cases of lung and colon
      cancer. The quantitative results obtained from the isotopic and non-isotopic
      methods are quite similar, further supporting that the use of non-isotopic analog
      peptide as internal standard is appropriate and feasible for the quantification
      of NQO1. By comparing with a classical isotopic IS, the present study indicates
      that the use of a non-isotopic peptide analog to the proteotypic peptide as the
      internal standard can get equal accuracy and preciseness in measuring NQO1. The
      universal applicability of the non-isotopic IS approach for the quantification of
      proteins warrants further research.

PMID- 23540249
TI  - Hyphenation of ionic liquid albumin glassy carbon biosensor or protein label-free
      sensor with differential pulse stripping voltammetry for interaction studies of
      human serum albumin with fenoprofen enantiomers.
AB  - A new biosensor or protein label-free sensor composed of 1-butyl-3
      methylimidazolium hexafluorophosphates (BMIMPF6)-human serum albumin (HSA) film
      on glassy carbon electrode (GCE) was produced. Unfortunately, the native proteins
      themselves are often unstable in physiological conditions. Here, we introduced
      conjugation with ionic liquid (IL) such as BMIMPF6 which improved the stability
      and binding affinity of protein onto GCE. A rapid, simple and reliable method for
      the chiral discrimination and real time protein binding studies of fenoprofen
      enantiomers with HSA was developed by hyphenating ionic liquid albumin glassy
      carbon (ILAGC) biosensor with differential pulse cathodic stripping voltammetry
      under physiological conditions. The electrochemical behavior of chiral fenoprofen
      was monitored by cyclic voltammetry, from which large response was obtained from
      l-fenoprofen. The surface coverage of fenoprofen enantiomers was calculated by
      double potential-step chronocoulometry. The binding constants of chiral
      fenoprofen with HSA were estimated to be 3.2*10(5)+/-0.3 L mol(-1) and
      0.8*10(4)+/-0.4 L mol(-1) for L- and D-fenoprofen, respectively giving acceptable
      precision (SD <= 0.4) and good agreement with the literature values. The
      competitive interactions of ibuprofen with fenoprofen enantiomers-HSA were
      studied giving a significant decreasing in the binding degrees of analytes to
      HSA. The reciprocal competitive experiments indicated that L-fenoprofen replaced
      D-fenoprofen from HSA. The proposed electrochemical biosensor holds great
      potential for chiral discrimination and real time binding studies of drugs with
      protein.

PMID- 23540250
TI  - Optimization of a lateral flow immunoassay for the ultrasensitive detection of
      aflatoxin M1 in milk.
AB  - A high sensitive immunoassay-based lateral flow device for semi-quantitatively
      determine aflatoxin M1 (AFM1) in milk was developed. Investigation and
      optimization of the competitor design and of the gold-labelling strategy allowed
      the attainment of the ultra-sensitive assessment of AFM1 contamination at
      nanograms per litre level (LOD 20 ng L(-1), IC50 99 ng L(-1)), as requested by
      European regulations. A one order of magnitude detectability enhancement in
      comparison to previously reported gold colloid immunochromatographic assays for
      this toxin was obtained. Direct detection of the target toxin in milk could be
      obtained by acquiring images of the strips and correlating intensities of the
      coloured lines with analyte concentrations. The one-step assay can be completed
      in 17 min, including a very simple and rapid sample preparation, which allowed
      the application of the assay to milk samples which differ in fat and protein
      contents. Although imprecise (mean RSD about 30%), the method proved to be
      accurate and sensitive enough to allow the correct attribution of sample as
      compliant or non-compliant according to EU legislation in force. Agreeing results
      to those of a reference ELISA were obtained on 40 milk samples by matrix-matched
      calibration in pasteurized milk.

PMID- 23540251
TI  - Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for
      glucose.
AB  - Creation and application of noble metal nanoclusters have received continuous
      attention. By integrating enzyme activity and fluorescence for potential
      applications, enzyme-capped metal clusters are more desirable. This work
      demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold
      cluster as probe for glucose. Under physiological conditions, such bioconjugate
      was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl)
      phosphonium-protected gold nanoparticle and thioctic acid-modified glucose
      oxidase were used as precursor and etchant, respectively. These bioconjugates
      showed unique fluorescence spectra (lambda(em max)=650 nm, lambda(ex max)=507 nm)
      with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose
      oxidase remained active and catalyzed reaction of glucose and dissolved O2 to
      produce H2O2, which quenched quantitatively the fluorescence of gold clusters and
      laid a foundation of glucose detection. A linear range of 2.0*10(-6)-140*10(-6)M
      and a detection limit of 0.7*10(-6)M (S/N=3) were obtained. Also, another
      horseradish peroxidase/gold cluster bioconjugate was produced by such general
      synthesis method. Such enzyme/metal cluster bioconjugates represented a promising
      class of biosensors for biologically important targets in organelles or cells.

PMID- 23540252
TI  - Quantitative detection of well-based DNA array using switchable lanthanide
      luminescence.
AB  - In this report a novel wash-free method for multiplexed DNA detection is
      demonstrated employing target specific probe pairs and switchable lanthanide
      luminescence technology on a solid-phase array. Four oligonucleotide capture
      probes, conjugated at 3' to non-luminescent lanthanide ion carrier chelate, were
      immobilized as a small array on the bottom of a microtiter plate well onto which
      a mix of corresponding detection probes, conjugated at 5' to a light absorbing
      antenna ligand, were added. In the presence of complementary target nucleic acid
      both the spotted capture probe and the liquid-phase detection probe hybridize
      adjacently on the target. Consequently the two non-luminescent label molecules
      self-assemble and form a luminescent mixed lanthanide chelate complex. Lanthanide
      luminescence is thereafter measured without a wash step from the spots by
      scanning in time-resolved mode. The homogeneous solid-phase array-based method
      resulted in quantitative detection of synthetic target oligonucleotides with 0.32
      nM and 0.60 nM detection limits in a single target and multiplexed assay,
      respectively, corresponding to 3* SD of the background. Also qualitative
      detection of PCR-amplified target from Escherichia coli is described.

PMID- 23540253
TI  - Practical considerations for preparing polymerized phospholipid bilayer capillary
      coatings for protein separations.
AB  - Phosphorylcholine (PC) based phospholipid bilayers have proven useful as
      capillary coating materials due to their inherent resistance to non-specific
      protein adsorption. The primary limitation of this important class of capillary
      coatings remains the limited long-term chemical and physical stability of the
      coatings. Recently, a method for increasing phospholipid coating stability in
      fused silica capillaries via utilization of polymerized, synthetic phospholipids
      was reported. Here, we expand upon these studies by investigating polymerized
      lipid bilayer capillary coatings with respect to separation performance including
      run-to-run, day-to-day and column-to-column reproducibility and long-term
      stability. In addition, the effects of pH and capillary inner diameter on
      polymerized phospholipid coated capillaries were investigated to identify
      optimized coating conditions. The coatings are stabilized for protein separations
      across a wide range of pH values (4.0-9.3), a unique property for capillary
      coating materials. Additionally, smaller inner diameter capillaries (<=50 MUm)
      were found to yield marked enhancements in coating stability and reproducibility
      compared to wider bore capillaries, demonstrating the importance of capillary
      size for separations employing polymerized phospholipid coatings.

PMID- 23540254
TI  - The effect of mitochondrial calcium uniporter opener spermine on diazoxide
      against focal cerebral ischemia--reperfusion injury in rats.
AB  - BACKGROUND: Recent research has indicated that mitochondrial adenosine
      triphosphate-sensitive potassium channels play an important role in cerebral
      protection, which involves in attenuating the calcium of mitochondria. However,
      the effect of diazoxide on cerebral ischemia-reperfusion and the role of
      spermine, the agonist of mitochondrial calcium uniporter (MCU), remain unknown.
      OBJECTIVE: We investigated the effect of MCU opener spermine on diazoxide against
      focal cerebral ischemia-reperfusion injury in rats. METHODS: Adult male Wistar
      rats were randomly divided into 5 groups: the Sham group, the I/R group, the Dzx
      + I/R group, the Dzx + Sper + I/R group, and the Sper + I/R group. Rats were
      exposed to 2-hour ischemia and 24-hour reperfusion. Diazoxide were administrated
      30 minutes before ischemia, and spermine were given 10 minutes before
      reperfusion. Rats in the Sham group did not experience the process of ischemia
      reperfusion. After 24-hour reperfusion, rats were given neurological performance
      tests, overdosed with general anesthesia, and then their brains were excised for
      infarct volume, pathological changes, and biochemical evaluation and analysis.
      RESULTS: Rats in the Dzx + I/R group displayed improved neurological deficits and
      decreased infarct volume and oxidative stress (evidenced by decreased nitric
      oxide and malondialdehyde but increased antioxidant enzymes [eg, glutathione
      peroxide and superoxide dismutase]) caused by ischemia-reperfusion. The
      beneficial effects of diazoxide were significantly attenuated by spermine
      treatment. Rats in the Sper + I/R group displayed worse neurological deficits,
      larger infarct volume and more oxidative stress, and less antioxidant enzymes
      than those in the Dzx + I/R. CONCLUSIONS: Our results suggested that diazoxide,
      which improved neurological deficits and decreased infarct volume and oxidative
      stress against ischemia-reperfusion injury, is mediated by spermine.

PMID- 23540255
TI  - The frequency of poststroke infections and their impact on early stroke outcome.
AB  - INTRODUCTION: Poststroke infections are the most common medical complications of
      stroke and can occur in up to 65% of patients. The aim of this study was to
      assess the rate of infectious complications during hospitalization of stroke
      patients and to evaluate the impact of infection in general, including each of
      the urinary tract infection (UTI), pneumonia, and sepsis, on fatal and poor
      functional outcome at discharge. METHODS: This retrospective study enrolled
      patients who have been diagnosed with acute ischemic stroke treated in a 1-year
      period. Poor functional outcome at discharge was defined as severe invalidity and
      included patients with modified Rankin Scale score of 3-5. Univariate and
      multivariate analyses were performed. RESULTS: We analyzed 133 patients with
      acute ischemic stroke. Poststroke infection occurred in 63 (47.4%) patients. The
      most common infection was UTI that was present in 27 (20.3%) patients.
      Multivariate logistic regression analysis after adjustment for confounders
      demonstrated that poststroke infection was an independent predictor of poor
      functional outcome (odds ratio [OR] 12.82, 95% confidence interval [CI] 4.09
      40.0, P < .001) and death at discharge (OR 14.92, 95% CI 2.97-76.92, P = .001).
      When analyzing the impact of each infectious complication, multivariate logistic
      regression showed that UTIs were an independent predictor of poor functional
      outcome (OR 14.08, 95% CI 3.06-64.84, P = .001) and death (OR 9.81, 95% CI 1.46
      65.68, P = .019) at discharge. CONCLUSION: Infection is a frequent poststroke
      complication and represents an independent predictor of poor functional and fatal
      early stroke outcome.

PMID- 23540256
TI  - Laterality of bolus passage through the pharynx in patients with unilateral
      medullary infarction.
AB  - Laterality of bolus passage in the pharynx is often seen in patients with
      medullary infarction. We evaluated the dominant side of bolus passage in the
      pharynx and investigated the factors that cause the passage to dominantly occur
      on the affected side. Forty-one patients (35 men and 6 women, 64 +/- 9 years)
      with unilateral medullary infarction participated in this study. Bolus passage of
      4 mL of thick liquid was evaluated in 3 regions (oropharyngeal, thyropharyngeal,
      and cricopharyngeal) and classified into 4 patterns (dominantly on the unaffected
      side [UAS], on both sides without clear laterality [BS], dominantly on the
      affected side [AS], and nonpassage of the bolus [NP]) by videofluoroscopic
      examination of swallowing. The bolus passages were as follows: UAS, BS, and AS
      occurred in 2, 32, and 7 patients in the oropharyngeal region; UAS, BS, and AS
      occurred in 5, 20, and 16 patients in the thyropharyngeal region; and UAS, BS,
      AS, and NP occurred in 11, 9, 10, and 11 patients in the cricopharyngeal region,
      respectively. In the thyropharyngeal region, the proportion of patients in whom
      the swallowing reflex occurred when the bolus was in the oropharynx and the
      proportion of patients with unilateral pharyngeal constrictor paralysis were
      greater in patients whose bolus passage was AS than in patients whose passage was
      BS. This suggests that the bolus predominantly passed through the affected side
      of the thyropharyngeal portion because of the asymmetry of pharyngeal contraction
      during swallowing in the early period after onset. 

PMID- 23540257
TI  - [Electrophysiology and schizophrenic vulnerability: the N400 component as
      endophenotype candidate?].
AB  - Research on early stages of schizophrenia aims to provide early, objective, and
      stable markers of vulnerability. In this review, we first briefly describe the
      notion of such markers, or endophenotypes, notably in terms of stability,
      specificity and heritability. Among other empirical approaches, event-related
      potentials (ERPs) have been recently considered as putative endophenotypes. The
      N400 component is an event-related brain potential classically elicited during
      semantic processing, as suggested by a growing body of empirical studies with a
      large variety of paradigms. We provide here a short account of its typical
      descriptions and the interpretations of its functional significance. Then we
      describe the main current results about schizophrenic alterations of the N400
      component. Two levels of semantic processing (automatic spreading and controlled
      mechanisms) are disturbed in schizophrenia, even if the underlying mechanisms
      remain unclear or discussed. Several controversial issues may also need further
      research, such as the influence of symptomatology and evolution of schizophrenia.
      Another crucial topic concerns the putative schizophrenic specificity, and only
      little is known about possible alterations of N400 in affective disorders. We
      discuss the notion of heritability, mainly explored in current literature among
      people with schizotypal personality. Finally, even if N400 studies contribute to
      a better understanding of linguistic disturbances in schizophrenia, it appears
      difficult to consider the N400 component as a relevant schizophrenic
      endophenotype, given the current paucity of results on its stability, its
      heritability (clinical and genetic vulnerability) and its schizophrenic
      specificity.

PMID- 23540258
TI  - Electrophysiological pattern of 53 cases of ulnar nerve lesion at the wrist.
AB  - OBJECTIVE: We aimed to evaluate the relative diagnostic sensitivity and
      specificity of different motor and sensory conduction electrodiagnostic (EDX)
      tests used to demonstrate ulnar neuropathy at the wrist (UNW). We also reported
      some data on associated nerve lesions and unusual causes of UNW. PATIENTS AND
      METHODS: A prospective case series was conducted in 53 cases of UNW and 100 cases
      of ulnar neuropathy at elbow (UNE). All cases underwent the same EDX examination
      according to a protocol defined in 1997. A few cases required additional
      conduction tests with coaxial needle recording. RESULTS: The diagnostic
      sensitivity of the distal motor latency (DML) to adductor digiti minimi (ADM) and
      sensory conduction was 42% and 19% respectively. The diagnostic sensitivity of
      the DML to first dorsal interosseous (FDI) was 66% and studying conduction across
      the wrist to search for conduction block (CB) improved the diagnostic sensitivity
      up to 90%. In 10% of cases, no EDX test of this protocol allowed locating the
      site of the UNL. The specificity of each test was 100% for controls, and varied
      from 100% for conduction block (CB), to 95% (DML to FDI) for UNE. CB at the wrist
      in UNW was 2.7times more frequent than at the elbow in UNE (57% vs. 22%;
      P<0.0001). Finally, we found three cases of isolated sensory UNW, 16 of sensory
      and motor UNW, and 34 of pure motor lesions. A median nerve lesion at the wrist
      coexisted in 22 cases. CONCLUSIONS: Improving UNW diagnosis requires systematic
      study of the ulnar motor conduction to FDI across the wrist, and in a few cases
      conduction tests with a coaxial needle recording.

PMID- 23540259
TI  - Clinical and neurophysiological aspects of anatomical variants in dorsomedial
      hand innervation.
AB  - OBJECTIVE: Three patients presented with painful paraesthesias in the dorsomedial
      aspect of the hand after removal of a ganglion cyst of the dorsal lower third of
      the forearm. This hand territory is usually innervated by the dorsal cutaneous
      branch of the ulnar nerve (DCU) but here it was innervated by a branch of the
      radial superficial nerve (RS). Consequently, we aimed to examine the frequency of
      this variant in the general population. METHODS: Both RS and DCU were stimulated
      in the forearm and sensory response recorded from the dorsomedial skin area of
      the hand in the three patients and 100 normal controls. RESULTS: In all three
      patients, the RS nerve innervated the dorsomedial hand bilaterally. Nineteen out
      of 100 controls demonstrated variants of dorsomedial skin innervation of the hand
      on nerve conduction studies: 12 unilaterally and seven bilaterally. Among them,
      13 individuals had mixed innervation by both RS and DCU and six by the RS nerve
      only. CONCLUSION: Nerve conduction studies of both RS and DCU with sensory
      response recording on the dorsomedial hand area should be considered before
      surgical procedures on the dorsal lower forearm in order to prevent iatrogenic
      postoperative sensory nerves lesions.

PMID- 23540260
TI  - Circulating alpha-klotho levels in CKD and relationship to progression.
AB  - BACKGROUND: alpha-Klotho is reported to have protective effects against kidney
      injury, and its renal expression is decreased in many experimental models of
      kidney disease. However, circulating alpha-klotho levels in human chronic kidney
      disease (CKD) and the relationship to progression are unknown. STUDY DESIGN: Post
      hoc analysis of a prospective cohort study. SETTING & PARTICIPANTS: 243 of 301
      participants from a CKD cohort at our institution between January 2006 and
      December 2011 were eligible for the study. PREDICTOR: Baseline alpha-klotho
      levels. OUTCOMES: Primary outcome was the composite of doubling of baseline serum
      creatinine concentration, end-stage renal disease, or death. End-stage renal
      disease was defined as onset of treatment by renal replacement therapy.
      MEASUREMENTS: Serum alpha-klotho and fibroblast growth factor 23 (FGF-23) were
      measured using enzyme-linked immunosorbent assay. RESULTS: Lower serum alpha
      klotho levels were associated with more severe CKD stage in the cross-sectional
      analysis of the baseline data (P for trend < 0.001). In the adjusted
      multivariable linear regression model, log(alpha-klotho) was associated
      independently with estimated glomerular filtration rate (beta = 0.154; P =
      0.001). Cox regression analysis showed that baseline alpha-klotho level
      independently predicted the composite outcome after adjustment for age, diabetes,
      blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid
      hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94
      0.98; P < 0.001). When patients were categorized into 2 groups according to
      baseline median alpha-klotho value, 43 (35.2%) patients with alpha-klotho levels
      <=396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with
      alpha-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03).
      LIMITATIONS: Uncontrolled dietary phosphorus intake and use of frozen samples.
      CONCLUSIONS: This observational study showed that low circulating alpha-klotho
      levels were associated with adverse kidney disease outcome, suggesting that alpha
      klotho is a novel biomarker for CKD progression. More data from larger
      prospective longitudinal studies are required to validate our findings.

PMID- 23540262
TI  - Dasatinib-induced nephrotic-range proteinuria.
AB  - Since the introduction of imatinib, tyrosine kinase inhibition has been a
      mainstay in the treatment of many malignancies. The number of these medications
      is growing, as are the number of targeted tyrosine kinases. Off-target effects of
      these medications can have beneficial or adverse effects on the kidney. The onus
      of knowing the implications of these medications on kidney function, and
      appropriate treatment when such adverse effects occur, is on the nephrologist. We
      present a patient with chronic myelogenous leukemia who developed nephrotic-range
      proteinuria after initiation on dasatinib therapy that resolved after changing
      therapy to imatinib. The mechanism of kidney injury caused by dasatinib has not
      been described previously in the literature. We provide a review of vascular
      endothelial growth factor and its pharmacologic inhibition as it pertains to
      kidney pathology and propose possible mechanisms by which dasatinib induces
      kidney injury.

PMID- 23540261
TI  - Pilot study of a physician-delivered education tool to increase patient knowledge
      about CKD.
AB  - BACKGROUND: Limited research exists on physician-delivered education
      interventions. We examined the feasibility and impact of an educational tool on
      facilitating physician-patient kidney disease communication. STUDY DESIGN: Pilot
      feasibility clinical trial with a historical control to examine effect size on
      patient knowledge and structured questions to elicit physician and patient
      feedback. SETTING & PARTICIPANTS: Adults with chronic kidney disease (CKD) stages
      1-5, seen in nephrology clinic. INTERVENTION: 1-page educational worksheet,
      reviewed by physicians with patients. OUTCOMES: Kidney knowledge between patient
      groups and provider/patient feedback. MEASUREMENTS: Patient kidney knowledge was
      measured using a previously validated questionnaire compared between patients
      receiving the intervention (April to October 2010) and a historical cohort (April
      to October 2009). Provider input was obtained using structured interviews.
      Patient input was obtained through survey questions. Patient characteristics were
      abstracted from the medical record. RESULTS: 556 patients were included, with 401
      patients in the historical cohort and 155 receiving the intervention. Mean age
      was 57 +/- 16 (SD) years, with 53% men, 81% whites, and 78% with CKD stages 3-5.
      Compared with the historical cohort, patients receiving the intervention had
      higher adjusted odds of knowing they had CKD (adjusted OR, 2.20; 95% CI, 1.16
      4.17; P = 0.02), knowing their kidney function (adjusted OR, 2.25; 95% CI, 1.27
      3.97; P = 0.005), and knowing their stage of CKD (adjusted OR, 3.22; 95% CI, 1.49
      6.92; P = 0.003). Physicians found the intervention tool easy and feasible to
      integrate into practice and 98% of patients who received the intervention
      recommended it for future use. LIMITATIONS: Study design did not randomly assign
      patients for comparison and enrollment was performed in clinics at one center.
      CONCLUSIONS: In this pilot study, a physician-delivered education intervention
      was feasible to use in practice and was associated with higher patient kidney
      disease knowledge. Further examination of physician-delivered education
      interventions for increasing patient disease understanding should be tested
      through randomized trials.

PMID- 23540263
TI  - Ophthalmic vein compression for selected benign low-flow cavernous sinus dural
      arteriovenous fistulas.
AB  - Dural arteriovenous fistulas (DAVFs) of the cavernous sinus are acquired
      arteriovenous shunts between the dural branches of the internal and external
      carotid arteries and the cavernous sinus. These fistulas may present with
      cortical venous reflux, but more commonly drain antegradely toward the superior
      ophthalmic vein (SOV). Transvenous embolization is the most common endovascular
      treatment, but in some cases transvenous access to the compartment of the shunt
      may not be possible. In cases with no corticovenous reflux, manual compression of
      the SOV is an excellent alternative treatment, which is well known but rarely
      reported in the literature. The authors describe a series of 3 cavernous DAVFs
      with anterior drainage treated successfully by intermittent manual compression of
      the SOV. 

PMID- 23540264
TI  - Editorial: Multiple metastases.

PMID- 23540265
TI  - Gamma Knife surgery for the treatment of 5 to 15 metastases to the brain:
      clinical article.
AB  - OBJECT: It has been generally accepted that Gamma Knife surgery (GKS) is an
      effective primary or adjunct treatment for patients with 1-4 metastases to the
      brain. The number of studies detailing the use of GKS for 5 or more brain
      metastases, however, remains minimal. The aim of the current retrospective study
      was to elucidate the utility of GKS in patients with 5-15 brain metastases.
      METHODS: Patients were chosen for GKS based on prior MRI of these metastatic
      lesions and a known primary cancer diagnosis. Magnetic resonance imaging was used
      post-GKS to assess tumor control; patients were also followed up clinically.
      Overall survival (OS) from the date of GKS was used as the primary end point.
      Statistical analysis was performed to identify prognostic factors related to OS.
      RESULTS: Between 2003 and 2012, 96 patients were treated for a total of 704
      metastatic brain lesions. The histology of these lesions varied among non-small
      cell lung cancer (NSCLC), breast cancer, melanoma, renal cancer, and other more
      rare carcinomas. At the initial treatment, 18 of the patients (18.8%) were
      categorized in Recursive Partitioning Analysis (RPA) Class 1 and 77 (80.2%) in
      RPA Class 2; none were in RPA Class 3. The median number of treated lesions was 7
      (mean 7.13), and the median planned treatment volume was 6.12 cm(3) (range 0.42
      57.83 cm(3)) per patient. The median clinical follow-up was 4.1 months (range 0.1
      40.70 months). Actuarial tumor control was calculated to be 92.4% at 6 months,
      84.8% at 12 months, and 74.9% at 24 months post-GKS. The median OS was found to
      be 4.73 months (range 0.4-41.8 months). Multivariate analysis demonstrated that
      RPA class was a significant predictor of death (HR = 2.263, p = 0.038). Number of
      lesions, tumor histology, Graded Prognostic Assessment score, prior whole-brain
      radiation therapy, prior resection, prior chemotherapy, patient age, patient sex,
      controlled primary tumor, extracranial metastases, and planned treatment volume
      were not significant predictors of OS. CONCLUSIONS: In patients with 5-15 brain
      metastases at presentation, the number of lesions did not predict survival after
      GKS; however, the RPA class was predictive of OS in this group of patients. Gamma
      Knife surgery for such patients offers an excellent rate of local tumor control.

PMID- 23540266
TI  - Detection of beta-amyloid oligomers as a predictor of neurological outcome after
      brain injury.
AB  - OBJECT: Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer
      like dementia. In previous studies, an increase in beta-amyloid (Abeta) monomers,
      such as beta-amyloid 42 (Abeta42), in the CSF of patients with TBI has been shown
      to correlate with a decrease in amyloid plaques in the brain and improved
      neurological outcomes. In this study, the authors hypothesized that the levels of
      toxic high-molecular-weight beta-amyloid oligomers are increased in the brain and
      are detectable within the CSF of TBI patients with poor neurological outcomes.
      METHODS: Samples of CSF were collected from 18 patients with severe TBI (Glasgow
      Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected
      within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and
      Abeta42 were measured using enzyme-linked immunosorbent assay. The levels of high
      molecular-weight beta-amyloid oligomers were measured using Western blot
      analysis. RESULTS: Patients with good outcomes showed an increase in the levels
      of CSF Abeta42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF
      levels of beta-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition,
      the CSF oligomer levels correlated with the scores on the extended Glasgow
      Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77,
      p = 0.005), CSF Abeta42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r =
      0.70, p = 0.004). Additionally, the receiver operating characteristic curve
      yielded an area under the curve for beta-amyloid oligomers of 0.8750 +/- 0.09.
      CONCLUSIONS: Detection of beta-amyloid oligomers may someday become a useful
      clinical tool for determining injury severity and neurological outcomes in
      patients with TBI.

PMID- 23540267
TI  - Editorial: Beyond diffusion tensor imaging.

PMID- 23540268
TI  - "Imagine your neighbor mows the lawn": a pilot study of psychological sequelae
      due to awake craniotomy: clinical article.
AB  - OBJECT: Although it has been reported that awake neurosurgical procedures are
      well tolerated, the long-term occurrence of general psychological sequelae has
      not yet been investigated. This study assessed the frequency and effects of
      psychological symptoms after an awake craniotomy on health-related quality of
      life (HRQOL). METHODS: Sixteen patients undergoing an awake surgery were surveyed
      with a self-developed questionnaire, the Posttraumatic Stress Disorder Inventory
      For Awake Surgery Patients, which adopts the core components of the Diagnostic
      and Statistical Manual of Mental Disorders (Fourth Edition) posttraumatic stress
      disorder (PTSD) criteria. The mean time between surgery and data collection was
      97.3 +/- 93.2 weeks. Health-related quality of life was assessed with the 36-Item
      Short Form Health Survey. RESULTS: Forty-four percent of the patients stated that
      they had experienced either repetitive distressing recollections or dreams
      related to the awake surgery, 18.8% stated persistent avoidance of stimuli
      associated with the awake surgery, and symptoms of increased arousal occurred in
      62.5%. Two patients presented with postoperative psychological sequelae
      resembling PTSD symptoms. Younger age at surgery and female sex were risk factors
      for symptoms of increased arousal. The experience of intense anxiety during awake
      surgery appears to favor the development of postsurgical PTSD symptoms, while
      recurrent distressing recollections particularly affect HRQOL negatively.
      CONCLUSIONS: In many cases awake craniotomy is necessary to preserve language and
      motor function. However, in some cases awake craniotomy can lead to postoperative
      psychological sequelae resembling PTSD symptoms. Therefore, possible long-term
      effects of an awake surgery should be considered and discussed with the patient
      when planning this type of surgery.

PMID- 23540269
TI  - White matter fiber tractography: why we need to move beyond DTI.
AB  - OBJECT: Diffusion-based MRI tractography is an imaging tool increasingly used in
      neurosurgical procedures to generate 3D maps of white matter pathways as an aid
      to identifying safe margins of resection. The majority of white matter fiber
      tractography software packages currently available to clinicians rely on a
      fundamentally flawed framework to generate fiber orientations from diffusion
      weighted data, namely diffusion tensor imaging (DTI). This work provides the
      first extensive and systematic exploration of the practical limitations of DTI
      based tractography and investigates whether the higher-order tractography model
      constrained spherical deconvolution provides a reasonable solution to these
      problems within a clinically feasible timeframe. METHODS: Comparison of
      tractography methodologies in visualizing the corticospinal tracts was made using
      the diffusion-weighted data sets from 45 healthy controls and 10 patients
      undergoing presurgical imaging assessment. Tensor-based and constrained spherical
      deconvolution-based tractography methodologies were applied to both patients and
      controls. RESULTS: Diffusion tensor imaging-based tractography methods (using
      both deterministic and probabilistic tractography algorithms) substantially
      underestimated the extent of tracks connecting to the sensorimotor cortex in all
      participants in the control group. In contrast, the constrained spherical
      deconvolution tractography method consistently produced the biologically expected
      fan-shaped configuration of tracks. In the clinical cases, in which tractography
      was performed to visualize the corticospinal pathways in patients with
      concomitant risk of neurological deficit following neurosurgical resection, the
      constrained spherical deconvolution-based and tensor-based tractography
      methodologies indicated very different apparent safe margins of resection; the
      constrained spherical deconvolution-based method identified corticospinal tracts
      extending to the entire sensorimotor cortex, while the tensor-based method only
      identified a narrow subset of tracts extending medially to the vertex.
      CONCLUSIONS: This comprehensive study shows that the most widely used clinical
      tractography method (diffusion tensor imaging-based tractography) results in
      systematically unreliable and clinically misleading information. The higher-order
      tractography model, using the same diffusion-weighted data, clearly demonstrates
      fiber tracts more accurately, providing improved estimates of safety margins that
      may be useful in neurosurgical procedures. We therefore need to move beyond the
      diffusion tensor framework if we are to begin to provide neurosurgeons with
      biologically reliable tractography information.

PMID- 23540270
TI  - Displacement of mammillary bodies by craniopharyngiomas involving the third
      ventricle: surgical-MRI correlation and use in topographical diagnosis.
AB  - OBJECT: Accurate diagnosis of the topographical relationships of
      craniopharyngiomas (CPs) involving the third ventricle and/or hypothalamus
      remains a challenging issue that critically influences the prediction of risks
      associated with their radical surgical removal. This study evaluates the
      diagnostic accuracy of MRI to define the precise topographical relationships
      between intraventricular CPs, the third ventricle, and the hypothalamus. METHODS:
      An extensive retrospective review of well-described CPs reported in the MRI era
      between 1990 and 2009 yielded 875 lesions largely or wholly involving the third
      ventricle. Craniopharyngiomas with midsagittal and coronal preoperative and
      postoperative MRI studies, in addition to detailed descriptions of clinical and
      surgical findings, were selected from this database (n = 130). The position of
      the CP and the morphological distortions caused by the tumor on the sella
      turcica, suprasellar cistern, optic chiasm, pituitary stalk, and third ventricle
      floor, including the infundibulum, tuber cinereum, and mammillary bodies (MBs),
      were analyzed on both preoperative and postoperative MRI studies. These changes
      were correlated with the definitive CP topography and type of third ventricle
      involvement by the lesion, as confirmed surgically. RESULTS: The mammillary body
      angle (MBA) is the angle formed by the intersection of a plane tangential to the
      base of the MBs and a plane parallel to the floor of the fourth ventricle in
      midsagittal MRI studies. Measurement of the MBA represented a reliable
      neuroradiological sign that could be used to discriminate the type of
      intraventricular involvement by the CP in 83% of cases in this series (n = 109).
      An acute MBA (< 60 degrees ) was indicative of a primary tuberal-intraventricular
      topography, whereas an obtuse MBA (> 90 degrees ) denoted a primary suprasellar
      CP position, causing either an invagination of the third ventricle
      (pseudointraventricular lesion) or its invasion (secondarily intraventricular
      lesion; p < 0.01). A multivariate model including a combination of 5 variables
      (the MBA, position of the hypothalamus, presence of hydrocephalus, psychiatric
      symptoms, and patient age) allowed an accurate definition of the CP topography
      preoperatively in 74%-90% of lesions, depending on the specific type of
      relationship between the tumor and third ventricle. CONCLUSIONS: The type of
      mammillary body displacement caused by CPs represents a valuable clue for
      ascertaining the topographical relationships between these lesions and the third
      ventricle on preoperative MRI studies. The MBA provides a useful sign to
      preoperatively differentiate a primary intraventricular CP originating at the
      infundibulotuberal area from a primary suprasellar CP, which either invaginated
      or secondarily invaded the third ventricle.

PMID- 23540271
TI  - Colocalization of thin-walled dome regions with low hemodynamic wall shear stress
      in unruptured cerebral aneurysms.
AB  - OBJECT: Wall shear stress (WSS) plays a role in regulating endothelial function
      and has been suspected in cerebral aneurysm rupture. The aim of this study was to
      evaluate the spatial relationship between localized thinning of the aneurysm dome
      and estimated hemodynamic factors, hypothesizing that a low WSS would correlate
      with aneurysm wall degeneration. METHODS: Steady-state computational fluid
      dynamics analysis was performed on 16 aneurysms in 14 patients based on
      rotational angiographic volumes to derive maps of WSS, its spatial gradient
      (WSSG), and pressure. Local dome thickness was estimated categorically based on
      tissue translucency from high-resolution intraoperative microscopy findings. Each
      computational model was oriented to match the corresponding intraoperative view
      and numerically sampled in thin and normal adjacent dome regions, with controls
      at the neck and parent vessel. The pressure differential was computed as the
      difference between aneurysm dome points and the mean neck pressure. Pulsatile
      time-dependent confirmatory analysis was carried out in 7 patients. RESULTS:
      Matched-pair analysis revealed significantly lower levels of WSS (0.381 Pa vs
      0.816 Pa; p<0.0001) in thin-walled dome areas than in adjacent baseline thickness
      regions. Similarly, log WSSG and log WSS*WSSG were both lower in thin regions
      (both p<0.0001); multivariate logistic regression analysis identified lower WSS
      and higher pressure differential as independent correlates of lower wall
      thickness with an area under the curve of 0.80. This relationship was observed in
      both steady-state and time-dependent pulsatile analyses. CONCLUSIONS: Thin-walled
      regions of unruptured cerebral aneurysms colocalize with low WSS, suggesting a
      cellular mechanotransduction link between areas of flow stasis and aneurysm wall
      thinning.

PMID- 23540272
TI  - Infarction of the lateral posterior choroidal artery territory after manipulation
      of the choroid plexus at the atrium: causal association with subependymal artery
      injury.
AB  - OBJECT: The atrium of the lateral ventricle is often affected by tumors, and some
      patients with these tumors suffer neurological deficits, including hemiparesis
      after surgery. The authors of this study investigated the possible mechanisms
      causing the relatively high incidences of ischemic complications associated with
      surgery approaching the atrium of the lateral ventricle. METHODS: Clinical
      records and radiological images of 28 patients were retrospectively studied.
      These patients had their lateral ventricles opened at the atrium during the
      resection of gliomas as well as other nonbenign brain tumors, and were treated
      for gliomas at our tertiary referral center in the Tohoku district, Japan,
      between January 2008 and December 2010. RESULTS: Routine postoperative diffusion
      weighted MR images obtained within 72 hours after surgery detected infarction in
      the periatrial/periventricular regions in 7 patients, presumably corresponding to
      the lateral posterior choroidal artery (LPChA) territory. Five of these 7
      patients suffered neurological sequelae with varying severities. The choroid
      plexus at the atrium was coagulated to achieve hemostasis during the surgery in
      all of these patients. Detailed analysis of microangiograms revealed
      ventriculofugal arteries arising from the lateral ventricle. Damage of the
      subependymal artery that supplies the ventriculofugal arteries caused by
      coagulation of the choroid plexus at the atrium probably resulted in the
      infarction in these patients. CONCLUSIONS: Neurosurgeons must be aware of the
      possibility of LPChA territory infarction during surgery in the atrial or
      periatrial regions caused by subependymal artery obstruction after manipulating
      or coagulating the choroid plexus near the atrium.

PMID- 23540273
TI  - The effect of age on fluid intelligence is fully mediated by physical health.
AB  - The present study investigated the extent to which the effect of age on cognitive
      ability is predicted by individual differences in physical health. The sample
      consisted of 118 volunteer subjects who were healthy and ranging in age from 26
      to 91. The examinations included a clinical investigation, magnetic resonance
      imaging (MRI) brain neuroimaging, and a comprehensive neuropsychological
      assessment. The effect of age on fluid IQ with and without visual spatial praxis
      and on crystallized IQ was tested whether being fully-, partially- or non
      mediated by physical health. Structural equation analyses showed that the best
      and most parsimonious fit to the data was provided by models that were fully
      mediated for fluid IQ without praxis, non-mediated for crystallized IQ and
      partially mediated for fluid IQ with praxis. The diseases of the circulatory and
      nervous systems were the major mediators. It was concluded from the pattern of
      findings that the effect of age on fluid intelligence is fully mediated by
      physical health, while crystallized intelligence is non-mediated and visual
      spatial praxis is partially mediated, influenced mainly by direct effects of age.
      Our findings imply that improving health by acting against the common age-related
      circulatory- and nervous system diseases and risk factors will oppose the decline
      in fluid intelligence with age.

PMID- 23540274
TI  - Alder-ene reactions of arynes.
AB  - Efficient Alder-ene reactions of various arynes generated directly from bis-1,3
      diynes are described. The reactivity of ene donors with different tethers was
      examined under thermal and metal-catalyzed conditions, which indicates that both
      the formation of aryne intermediates and their ene reactions are less sensitive
      to the catalyst than to the structural features of the substrates.

PMID- 23540275
TI  - Tales of telemedicine--telepsychiatry at work.

PMID- 23540276
TI  - Feasibility of dynamic telecytopathology for rapid on-site evaluation of
      endobronchial ultrasound-guided transbronchial fine needle aspiration.
AB  - OBJECTIVE: Rapid on-site evaluation (ROSE) at the time of endobronchial
      ultrasound-guided transbronchial fine needle aspiration (EBUS-TBFNA) is useful in
      obtaining adequate samples and providing preliminary diagnosis. We present our
      experience with ROSE of EBUS-TBFNA using telecytopathology. MATERIALS AND
      METHODS: Real-time images of Diff-Quik (Mercedes Medical, Sarasota, FL)-stained
      cytology smears were obtained with an Olympus (Olympus America, Center Valley,
      PA) digital camera attached to an Olympus CX41 microscope and transmitted via
      ethernet by a cytotechnologist to a cytopathologist in a cytopathology laboratory
      who rendered a preliminary diagnosis while communicating with an on-site
      cytotechnologist via the Vocera (San Jose, CA) voice communication system. The
      endoscopy suite was located a block away from the cytopathology laboratory.
      Accuracy of ROSE via telecytopathology was compared with an equal number of cases
      that received ROSE, prior to introduction of telecytopathology, via conventional
      microscopy. RESULTS: ROSE was performed on a total of 200 EBUS-TBFNAs. The
      telecytopathology system and conventional microscopy were used to evaluate equal
      numbers of cases (100 each). Preliminary diagnoses of negative/benign,
      atypical/suspicious, and positive for malignancy were 58%, 14%, and 24% for
      telecytopathology and 57%, 10%, and 31% for conventional microscopy. Four percent
      of telecytopathology cases and 2% of conventional microscopy cases were deemed
      unsatisfactory at the time of ROSE. The overall concordance between the
      preliminary and final diagnoses was 96% for telecytopathology and 93% for
      conventional microscopy. The causes of discordant preliminary and final diagnoses
      could be mainly attributed to difficulty in distinguishing small cell carcinoma
      versus reactive lymph node due to crush artifact, atypia related to reactive
      bronchial epithelial cells, and availability of cell block material and
      Papanicolaou-stained slides for review at the time of final cytologic sign out.
      CONCLUSIONS: Telecytopathology is comparable with conventional microscopy in ROSE
      of EBUS-TBFNA. It can serve as a valid substitute for conventional microscopy for
      on-site assessment of EBUS-TBFNA.

PMID- 23540277
TI  - Viable investigations and real-time recitation of enhanced ECG-based cardiac
      telemonitoring system for homecare applications: a systematic evaluation.
AB  - A light and portable wireless biosignal retrieving system has always been a
      medical dream. This proposed wireless-type biosignal alerting system aims at
      designing and developing a module that detects the abnormal interpretations in
      the PQRST complex (electrocardiography) and heart rate of a patient in advance,
      gives a self-warning ring to the patient, and also sends a short message service
      warning to the doctor's mobile phone through the Global System for Mobile
      Communication. This system is a solution to supplement the limitations in
      conventional clinic examination such as the difficulty in capturing rare events,
      out-of-hospital monitoring of patients' heart status, and the immediate
      dissemination of the physician's instruction to the patient. These study results
      have immense consequence in researching, finding, and preventing epidemics in the
      cardiovascular system for the entire world.

PMID- 23540278
TI  - A review of telemedicine business models.
AB  - Telemedicine has become an increasingly popular option for long-distance/virtual
      medical care and education, but many telemedicine ventures fail to grow beyond
      the initial pilot stage. Studying the business models of successful telemedicine
      ventures can help develop business strategies for upcoming ventures. This article
      describes business models of eight telemedicine ventures from different regions
      of the world using Osterwalder's "Business Model Canvas." The ventures are chosen
      on the basis of their apparent success and their diverse value chains. The
      business models are compared to draw inferences and lessons regarding their
      business strategy and contextual factors that influenced it. Key differences
      between telemedicine business practices in developing and developed countries are
      also discussed. The purpose of this article is to inform and inspire the business
      strategy of the next generation of telemedicine ventures to be economically
      sustainable and to successfully address local healthcare challenges.

PMID- 23540279
TI  - Feasibility of adapting a classroom balance training program to a video game
      platform for people with Parkinson's disease.
AB  - OBJECTIVE: Decreased postural stability in people with Parkinson's disease (PD)
      is a major component of disability. Rehabilitation interventions are therefore
      targeted to improve balance, mobility, and strength. Virtual environment and
      gaming platforms can encourage therapeutic activity in the home and be
      challenging and fun. The aims of the project were to demonstrate the technical
      feasibility of adapting a classroom-based gait-and-balance training program to a
      video game platform. Ease of use, appeal, and safety of the proposed games were
      tested for both clinic and in-home use. SUBJECTS AND METHODS: This cross
      sectional observational study was carried out in three phases. Modifications in
      the game platform were made in an iterative fashion based on feedback from
      subjects and the observations of clinical and design team members. The first two
      phases of testing were performed in a laboratory setting, and the final phase was
      carried out in subjects' homes. RESULTS: Subjects (n=20) scored the primary "Rail
      Runner" game 3.6 for ease of use (1=hard, 5=easy) and 3.9 for appeal (1=did not
      like at all, 5=liked very much). There were no safety issues encountered, and the
      games performed without technical flaws in the final phase of testing.
      CONCLUSIONS: A computer-based video game that incorporates therapeutic movements
      to improve gait and balance for people with PD was appealing to subjects and
      feasible for home use.

PMID- 23540280
TI  - Effect of culture on acceptance of telemedicine in Middle Eastern countries: case
      study of Jordan and Syria.
AB  - We investigated issues that affect the use and adoption of telemedicine in Middle
      Eastern countries, taking the Hashemite Kingdom of Jordan and the Syrian Arab
      Republic as case studies. Our study is based on interviews with key stakeholders
      (including doctors, technicians, engineers, and decision makers) and
      questionnaires administered to key stakeholders (including patients), ensuring
      opinion was gained from people from a full range of backgrounds and roles in the
      healthcare system. We found doctor and patient resistance was a major issue
      preventing the adoption of telemedicine in both countries, followed by poor
      infrastructure, lack of funding, and lack of information technology training. Our
      research identifies that culture is a greater issue than technical matters for
      the adoption of telemedicine in Middle Eastern countries. Based on our
      preliminary results we developed a guideline framework for each country that
      might be applied to telemedicine projects at the pre-implementation phase. The
      proposed guideline framework was validated through a return visit to the
      stakeholders and seeking further opinion.

PMID- 23540281
TI  - Repetitive transcranial magnetic stimulation elicits rate-dependent brain network
      responses in non-human primates.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) has the potential to treat
      brain disorders by tonically modulating firing patterns in disease-specific
      neural circuits. The selection of treatment parameters for clinical repetitive
      transcranial magnetic stimulation (rTMS) trials has not been rule based, likely
      contributing to the variability of observed outcomes. OBJECTIVE: To utilize our
      newly developed baboon (Papio hamadryas anubis) model of rTMS during position
      emission tomography (PET) to quantify the brain's rate-response functions in the
      motor system during rTMS. METHODS: We delivered image-guided, suprathreshold rTMS
      at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the
      primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging;
      we also administered a (reversible) paralytic to eliminate any somatosensory
      feedback due to rTMS-induced muscle contractions. Each rTMS/PET session was
      analyzed using normalized cerebral blood flow (CBF) measurements; statistical
      parametric images and the resulting areas of significance underwent post-hoc
      analysis to determine any rate-specific rTMS effects throughout the motor
      network. RESULTS: The motor system's rate-response curves were unimodal and
      system wide--with all nodes in the network showing highly similar rate response
      functions--and an optimal network stimulation frequency of 5 Hz. CONCLUSION(S):
      These findings suggest that non-invasive brain stimulation may be more
      efficiently delivered at (system-specific) optimal frequencies throughout the
      targeted network and that functional imaging in non-human primates is a promising
      strategy for identifying the optimal treatment parameters for TMS clinical trials
      in specific brain regions and/or networks.

PMID- 23540283
TI  - Conversion of estrone to 17 beta-estradiol in Jurkat acute T cell leukemia Hut-78
      T- and Raji B lymphoma cell lines in vitro.
AB  - Leukemia and lymphoma cells are positive for estrogen receptors and contain
      endogenous estrogens and estrogen metabolites. Therefore, we studied the levels
      of 17 beta-hydroxysteroid-dehydrogenase type 1 (HSD17B1) transcript and protein
      and the production of 17 beta-estradiol (E2) from estrone (E1) in human Jurkat
      acute T cell leukemia, Hut-78 and Raji B lymphoma cells. We found the presence of
      HSD17B1 transcripts and proteins in these cells. Moreover, we demonstrated that
      Jurkat, Hut-78, and Raji B cells are able to produce E2 from E1. Our results
      indicate that Jurkat acute T cell leukemia, Hut-78 and Raji B lymphoma cells are
      able to convert weak estrogen E1 to the more potent E2 in vitro.

PMID- 23540282
TI  - Diphenyl diselenide protects cultured MCF-7 cells against tamoxifen-induced
      oxidative DNA damage.
AB  - Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a
      variety of pharmacologically active organoselenium compounds. Studies have shown
      its interesting pharmacodinamic properties, as antioxidant, antimutagenic and
      antitumoral effects. Here we report the antigenotoxic properties of DPDS against
      tamoxifen (TAM)-induced oxidative DNA damage in MCF-7 cultured cell line. We
      determined the cytotoxicity by lactate dehydrogenase (LDH) leakage assay and
      evaluated oxidative DNA damage by modified comet assay employing the enzymes
      formamidopyrimidine DNA-glycosylase (Fpg) and endonuclease III (Endo III). Our
      results demonstrate that the cellular effects of DPDS appear to be complex and
      concentration-dependent. The present findings show that DPDS is not genotoxic (at
      concentrations lower than 2.0MUmol/L) in MCF-7 cells, as observed in the modified
      comet assay. Moreover, DPDS protects against TAM-induced oxidative DNA damage,
      probably by its antioxidant activity, without interfering with its cytotoxicity.
      In this manner, the treatment with low concentrations of DPDS, a synthetic
      organoselenium compound, could be used as a potent antigenotoxic agent to prevent
      the risk of cancer induction triggered by tamoxifen hormone therapy. Thereby,
      more studies concerning the toxicity of DPDS and its structural derivatives are
      still necessary for future safe therapeutic application and development of novel
      chemopreventive compounds for combined therapy in breast cancer.

PMID- 23540284
TI  - Overcoming multidrug resistance using liposomal epirubicin and antisense
      oligonucleotides targeting pump and nonpump resistances in vitro and in vivo.
AB  - Multidrug resistance (MDR) is a serious obstacle in cancer treatment. In this
      study, epirubicin (Epi), an anthracycline antineoplastic agent, and/or antisense
      oligonucleotides (ASOs) targeting MDR1, MDR-associated protein (MRP)1, MRP2, and
      BCL-2/BCL-xL were incorporated into polyethylene glycol-coated (PEGylated)
      liposomes to develop a suitable anticancer drug delivery system. We evaluated in
      vitro cytotoxicity, intracellular accumulation and cell cycle analysis of these
      formulations. We also assessed in vivo pharmacokinetics and antitumor efficacy of
      these formulations in Sprague-Dawley (SD) rats and mouse colon adenocarcinoma
      CT26-bearing Balb/c mice. ASOs in PEGylated liposomes significantly enhanced the
      cytotoxicity and the intracellular accumulation of Epi in CT26 cells. This
      combination also intensified Epi-induced apoptosis in CT26 cells. An in vivo
      pharmacokinetic study using SD rats showed that after intravenous administration
      of PEGylated liposomal Epi and ASOs, Epi had greater area under the curve and
      longer half-life than in an Epi solution. The treatment of PEGylated liposomal
      Epi and ASOs also demonstrated significant improvements in tumor growth
      inhibition and survival percentage in CT26-bearing Balb/c mice in vivo. The
      PEGylated liposomal formulation of Epi and ASOs against MDR1, MRP1, MRP2, and BCL
      2/BCL-xL exhibited the most pronounced effect among all the formulations used in
      this study. This study pioneered in demonstrating that PEGylated liposomal ASOs
      targeting both pump and nonpump resistances increase antitumor efficacy in vivo
      through the simultaneous inhibition of MDR transporters and apoptosis induction.
      This approach provides a potential strategy to overcome MDR in cancer
      chemotherapy.

PMID- 23540285
TI  - Annexin A7 gene is an important factor in the lymphatic metastasis of tumors.
AB  - In the tumor malignancy progression, lymph node metastasis (LNM) is recognized as
      an important factor. In this study, RNA interference (RNAi) was employed to down
      regulate ANXA7 gene in Hca-F cells, a hepatocarcinoma cell line with high LNM
      rate. There was no significant effect on cell proliferation ability, but cell
      division, motility, and invasion abilities were markedly inhibited. By contrast,
      up-regulating the expression of ANXA7 gene in Hca-P cells with lower LNM rate,
      cell migration ability was improved and the percentage of cells in S phase was
      significantly decreased in vitro. Here, we reported that the expression of Ech1,
      GSN and JNK1 genes, which were relevant to tumor lymphatic metastasis, had been
      inhibited due to down-regulation ANXA7 gene and promoted due to up-regulation
      ANXA7 gene by western blot analysis. These results indicated that ANXA7 is a
      critical factor in the development of lymphatic metastasis in hepatocarcinoma
      progression.

PMID- 23540286
TI  - Thin-film growth and patterning techniques for small molecular organic compounds
      used in optoelectronic device applications.
AB  - Rapid advances in research and development in organic electronics have resulted
      in many exciting discoveries and applications, including organic light-emitting
      devices for information display and illumination, solar cells, photodetectors,
      chemosensors, and logic. Organic optoelectronic materials are broadly classified
      as polymeric or small molecular. For the latter category, solvent-free deposition
      techniques are generally preferred to form well-defined interfaces and improve
      device performance. This article reviews several deposition and patterning
      methods for small molecular thin films and devices, including organic molecular
      beam deposition, vacuum thermal evaporation, organic vapor phase deposition, and
      organic vapor jet printing, and compares them to several other methods that have
      been proposed recently. We hope this review provides a compact but informative
      summary of the state of the art in organic device processing and addresses the
      various techniques' governing physical principles.

PMID- 23540287
TI  - Biodegradable polyesters from renewable resources.
AB  - Environmental concerns have led to the development of biorenewable polymers with
      the ambition to utilize them at an industrial scale. Poly(lactic acid) and
      poly(hydroxyalkanoates) are semicrystalline, biorenewable polymers that have been
      identified as the most promising alternatives to conventional plastics. However,
      both are inherently susceptible to brittleness and degradation during thermal
      processing; we discuss several approaches to overcome these problems to create a
      balance between durability and biodegradability. For example, copolymers and
      blends can increase ductility and the thermal-processing window. Furthermore,
      chain modifications (e.g., branching/crosslinking), processing techniques (fiber
      drawing/annealing), or additives (plasticizers/nucleating agents) can improve
      mechanical properties and prevent thermal degradation during processing. Finally,
      we examine the impacts of morphology on end-of-life degradation to complete the
      picture for the most common renewable polymers.

PMID- 23540288
TI  - Metabolic engineering with plants for a sustainable biobased economy.
AB  - Plants are bona fide sustainable organisms because they accumulate carbon and
      synthesize beneficial metabolites from photosynthesis. To meet the challenges to
      food security and health threatened by increasing population growth and depletion
      of nonrenewable natural resources, recent metabolic engineering efforts have
      shifted from single pathways to holistic approaches with multiple genes owing to
      integration of omics technologies. Successful engineering of plants results in
      the high yield of biomass components for primary food sources and biofuel
      feedstocks, pharmaceuticals, and platform chemicals through synthetic biology and
      systems biology strategies. Further discovery of undefined biosynthesis pathways
      in plants, integrative analysis of discrete omics data, and diversified process
      developments for production of platform chemicals are essential to overcome the
      hurdles for sustainable production of value-added biomolecules from plants.

PMID- 23540289
TI  - Metabolic engineering: past and future.
AB  - We present here a broad overview of the field of metabolic engineering,
      describing in the first section the key fundamental principles that define and
      distinguish it, as well as the technological and intellectual developments over
      the past approximately 20 years that have led to the current state of the art.
      Discussion of concepts such as metabolic flux analysis, metabolic control
      analysis, and rational and combinatorial methods is facilitated by illustrative
      examples of their application drawn from the extensive metabolic engineering
      literature. In the second section, we present some of the rapidly emerging
      technologies that we think will play pivotal roles in the continued growth of the
      field, from improving production metrics to expanding the range of attainable
      compounds.

PMID- 23540290
TI  - Mixed semiconductor alloys for optical devices.
AB  - There is an increasing technological need for a wider array of semiconducting
      materials that will allow greater control over the physical and electronic
      structure within multilayer heterostructures. This need has led to an expansion
      in the range of semiconducting alloys explored and used in new applications.
      These alloy semiconductors are often complicated by a limited range of
      miscibility. The current research has focused on the properties, stability, and
      detailed chemistry required to realize these materials. The use of synthetic
      conditions that permit the growth of these alloys to be dominated by kinetic
      rather than mass-transport considerations has allowed many of these nominally
      unstable materials to be grown and used in device structures. These materials
      have found important applications within optical communications as emitters and
      detectors and in solid-state lighting.

PMID- 23540291
TI  - Rheology of slurries and environmental impacts in the mining industry.
AB  - The world's resource industries are the largest producers of waste. Much of this
      waste is produced as a fine particle slurry, which is pumped to a storage area,
      generally at a low concentration, where it behaves like a Newtonian fluid. Simply
      removing, reusing, and recycling water from the slurry represents a step toward a
      more sustainable practice in this industry. As the concentration of such a slurry
      is increased as a result of dewatering, the materials exhibit non-Newtonian
      behavior, which is characterized by shear thinning, a yield stress, and in some
      instances thixotropic behavior. Such high-concentration, nonideal (dirty)
      suspensions in the resource industries have meant that new rheological methods
      and techniques have been needed to measure and interpret the basic flow
      properties. Also, some older empirical techniques have needed to be modified and
      interpreted in a more fundamental way so that the results could be used in
      design. This article reviews these techniques and illustrates how the industry
      itself has motivated their development. Understanding and exploiting this
      rheology has resulted in dramatic improvement in the waste-disposal strategy for
      some industries, but many have failed to embrace the available technology. The
      reasons for this are discussed. The article concludes that a greater positive
      change in waste-management practice will occur in the future, motivated by
      several factors, including public perception, tighter regulation, and perhaps
      even commonsense life cycle accounting.

PMID- 23540292
TI  - Proteomics: from protein structures to clinical applications.

PMID- 23540293
TI  - The value of serum asymmetric dimethylarginine levels for the determination of
      masked hypertension in patients with diabetes mellitus.
AB  - BACKGROUND: An increased prevalence of masked hypertension (MHT) has been
      demonstrated among patients with diabetes mellitus (DM). MHT appears to cause
      cardiovascular (CV) complications similar to clinically overt hypertension.
      Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide inhibitor and
      higher plasma levels of ADMA are related to increased CV risk in both the general
      population and among patients with DM. The aim of this study was to evaluate the
      relationship between MHT and ADMA in diabetic patients. METHODS: This study
      included DM patients (n = 131) with normal office blood pressure (<140/90 mmHg).
      None of the participants were using antihypertensive medications. All
      participants utilized an ambulatory blood pressure monitor (ABPM) for 24 h. Serum
      ADMA and arginine levels were measured using the fluorescence detector high
      performance liquid chromatography method. RESULTS: The prevalence of MHT was
      24.4% among the study subjects. ADMA levels were increased in the MHT group when
      compared with normotensive diabetics (6.2 +/- 2.2 vs 4.2 +/- 1.7 MUmol/L p =
      0.001, respectively). Furthermore, arginine/ADMA ratio was lower in the MHT group
      than among the normotensive group (29.9 +/- 12.1 vs 46.0 +/- 19.0 p = 0.001). In
      the multivariate logistic regression model, ADMA, BMI and HDL levels were found
      to be independent predictors of MHT Odds ratio: 1.63 (1.28-2.06), 1.19 (1.05
      1.35), and 0.95 (0.90-0.99), respectively. The cut-off value of the ADMA was 4.34
      MUmol/L with a sensitivity, specificity, positive predictive value, and negative
      predictive value of 84.4%, 59.6%, of 40.3%, and 92.2%, respectively (AUC = 0.78).
      CONCLUSIONS: Serum ADMA may play a role in both the pathophysiology and screening
      of MHT in DM subjects.

PMID- 23540295
TI  - Biocatalysis enters a new era.

PMID- 23540294
TI  - Effects of obesity on the impact of short-term changes in anthropometric
      measurements on coronary heart disease in women.
AB  - OBJECTIVE: To assess the impact of short-term changes in body mass index (BMI),
      waist circumference (WC), hip circumference (HC), and waist-to-hip ratio on the
      risk of future coronary heart disease (CHD) among women. PARTICIPANTS AND
      METHODS: The study sample consisted of 2468 women aged 30 years or older without
      cardiovascular disease at baseline who underwent 2 consecutive examinations, the
      first between January 31, 1999, and August 21, 2001, and second between October
      20, 2001, and September 22, 2005, and were followed up until March 31, 2010. Cox
      proportional hazard regression was performed to estimate the hazard ratios (HRs)
      of the anthropometric measures for CHD events. RESULTS: During a mean follow-up
      of 6.6 years, CHD occurred in 127 of the study participants (5.1%). There were
      significant interactions between a BMI of 30 kg/m(2) or greater and
      anthropometric changes in prediction of CHD events (all P<.04). Among nonobese
      individuals, a 1-SD increase in HC changes, independent of WC and BMI changes,
      was inversely associated with risk of CHD events (HR, 0.60 [95% CI, 0.44-0.83]).
      Among obese individuals, a 1-SD increase in WC, independent of other changes,
      increased the risk of CHD. Conversely, a 1-SD increase in BMI decreased the risk
      of CHD by 35% (HR, 0.65 [95% CI, 0.45-0.94]). CONCLUSION: In this study, the
      impact of changes in anthropometric measures on CHD was modified by obesity at
      baseline. Among nonobese women, increases in HC could significantly reduce the
      risk of CHD events. Among obese individuals, although increases in WC were
      associated with a higher risk of CHD, increases in BMI decreased the risk.

PMID- 23540296
TI  - Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and
      prognosis of lung adenocarcinoma.
AB  - Metastasis is a major cause of cancer recurrence or death. This study attempted
      to quantitatively identify different proteins in metastatic lung adenocarcinoma.
      The N/T quotient [number of metastatic lymph nodes (n)/tumor diameter (cm)] was
      used to select samples with an extreme metastatic phenotype. Among the six fresh
      frozen lung adenocarcinoma specimens, the three showing the highest N/T quotient
      represented the metastatic group, and others with the greatest tumor diameters
      without metastasis represented the non-metastatic group. After 2-dimensional
      electrophoresis, the significantly different protein spots were selected by image
      analysis and analyzed with MALDI-TOF mass spectrometry. Acyl-CoA thioesterase 8
      isoform c (ACOT8) was one of most overexpressed proteins in the metastatic group,
      and it was validated by Western blot and immunohistochemical staining on 108
      paraffin-embedded tumor samples. High ACOT8 expression was correlated with lymph
      node metastasis (p=0.002), recurrence (p=0.034), predominant histologic subtypes
      (p=0.007), and higher stage (p=0.005). In multivariate analysis, high ACOT8
      expression was significantly associated with increased risks of lymph node
      metastasis (p=0.009) and cancer-related death (p=0.030), independent of clinical
      factors. ACOT8 may be a candidate prognostic biomarker and therapeutic target of
      lung adenocarcinoma.

PMID- 23540297
TI  - Enacting multiple methamphetamines: the ontological politics of public discourse
      and consumer accounts of a drug and its effects.
AB  - Over the last decade in Australia, methamphetamine has come to be seen as a
      significant issue for drug research, policy and practice. Concerns have been
      expressed over its potency, the increasing prevalence of its use and its
      potential for producing greater levels, and more severe forms, of harm compared
      to amphetamine or other drugs. In this article, we critically examine some of the
      ways in which methamphetamine and its effects are produced and reproduced within
      and through Australian public discourse, focusing in particular on the
      associations made between methamphetamine and psychosis. We show how public
      discourse enacts methamphetamine as an anterior, stable, singular and definite
      object routinely linked to the severe psychological 'harm' of psychosis. We
      contrast the enactment of methamphetamine within public discourse with how
      methamphetamine is enacted by consumers of the drug. In their accounts, consumers
      perform different methamphetamine objects and offer different interpretations of
      the relationships of these objects to psychological problems and of the
      ontological nature (i.e. relating to what is real, what is, what exists) of these
      problems. In examining public discourse and consumer accounts, we challenge
      conventional ontological understandings of methamphetamine as anterior, singular,
      stable and definite, and of its psychological effects as indicative of pathology.
      In line with recent critical social research on drugs, we draw on social studies
      of science and technology that focus on the performativity of scientific
      knowledge and material practices. We suggest that recognising the ontological
      contingency, and therefore the multiplicity, of methamphetamine offers a critical
      counterpoint to conventional research, policy and practice accounts of
      methamphetamine and its psychological effects.

PMID- 23540298
TI  - Barriers and facilitators for promotoras' success in delivering pesticide safety
      education to Latino farmworker families: La Familia Sana.
AB  - Despite widespread use of lay health advisor (LHA) programs, factors related to
      success of LHAs remain largely unexamined. This study describes experiences and
      personal transformations of LHAs (promotoras de salud) in a pesticide safety
      education program targeting farmworker families in North Carolina, using
      postintervention in-depth interviews conducted with 17 LHAs. LHAs identified
      assets and barriers that affected their success. LHAs also described increases in
      self-efficacy and empowerment resulting in perceived improvements in ability to
      teach and impact their community. Such positive changes are essential benefits to
      the LHAs. Evaluations that address these topics are needed to better understand
      continuity and attrition in LHA programs.

PMID- 23540299
TI  - Analysis of tractor-related deaths.
AB  - The aim of the study was to evaluate the properties of tractor-related death
      cases and discuss the precautions in order to prevent such events. For this aim,
      reports made between 2006 and 2009 by the First Specialty Board of Council of
      Forensic Medicine (FSBCFM), Turkey, were evaluated retrospectively. Forty-one
      tractor-related death cases were included in this study. Thirty-five (85.4%) of
      the cases were male. The mean age was 42.52 +/- 25.1 (with a range between 1 and
      84 years old). The average time interval between the incident and death was 13.76
      +/- 33.53 days (range: 0-176 days) and 20 (48.8%) cases died on the incident spot
      or during transportation to the hospital. Among the cases, 34.1% (n = 14) were
      drivers, whereas 39.0% (n = 16) were passengers and the remaining were
      pedestrians (26.9%, n = 11). The accident was caused by the tractor rolling over
      in 34.1%, the victim being run over in 22.0%, and the victim falling from the
      tractor or trailer in 22.0% of the cases. Most of the events (56.1%) occurred on
      the road. In conclusion, tractors must not be used as a transportation vehicle
      for passengers. Periodic training of drivers can be useful for reducing tractor
      related accidents.

PMID- 23540300
TI  - Farm machinery injuries: the 15-year experience at an urban joint trauma center
      system in a rural state.
AB  - Farm machinery is a major source of injury. The objective of this study is to
      characterize the incidence, injury characteristics, and outcomes of patients
      admitted with farm machinery injuries (FMIs) to an urban joint trauma system in a
      rural state. A retrospective 15-year review of the trauma registries of the two
      trauma centers that function as a single state-designated Level I joint trauma
      center system was conducted. There were 65 admissions for FMIs at hospital A and
      41 at hospital B; this represents under 0.4% of total trauma admissions. The
      patients ranged in age from 2 to 87 years. At hospital A, 89% of admitted
      patients sustained extremity injuries, 16% sustained torso trauma, 92% required
      surgical intervention, and the mortality rate was 0%. At hospital B, 60% of
      admitted patients sustained extremity injuries, 36.6% of patients sustained torso
      trauma, 63% required surgical intervention, and the mortality rate was 14.6%.
      Tractor-related injuries were responsible for 17% of admissions at hospital A and
      69% at hospital B. Of the six fatalities, five were tractor related. The data
      demonstrate that FMIs affect people in nearly all decades of life. FMIs at the
      two hospitals had differing injury characteristics and outcomes, in large part
      secondary to the differing frequency of tractor-related injuries. FMIs frequently
      required surgical intervention.

PMID- 23540301
TI  - Qualitative assessment of agritourism safety guidelines: a demonstration project.
AB  - In 2007, the National Children's Center for Rural and Agricultural Health and
      Safety (NCCRAHS) published Agritourism Health and Safety Guidelines for Children
      to provide helpful recommendations for protecting the health and safety of
      children visiting agritourism farms. Supplement A: Policies and Procedures Guide
      and Supplement B: Worksite Guide were subsequently published in 2009 and provided
      agritourism farms with checklists to use in reviewing, planning, and implementing
      their own health and safety practices. In order to better understand what would
      be required of a farm wishing to implement the guidelines using Supplements A and
      B, the North Carolina Agromedicine Institute conducted a single-family farm
      demonstration project with support from the NCCRAHS. The aims of the project were
      to (1) determine child health and safety risks associated with an existing
      agritourism farm; (2) determine the cost of making improvements necessary to
      reduce risks; and (3) use project findings to motivate other agritourism farms,
      Cooperative Extension agents, and agritourism insurers to adopt or recommend
      Agritourism Health and Safety Guidelines for Children for their own farms or
      farms with which they work. At the conclusion of the study, the target farm was
      in compliance with an average of 86.9% of items in Supplements A and B.
      Furthermore, 89% of individuals self-identifying as farmers or farm workers and
      100% of Cooperative Extension agents and agritourism insurers attending an end-of
      project workshop indicated their intent to adopt or recommend Agritourism Health
      and Safety Guidelines for Children for their own farms or farms with which they
      work.

PMID- 23540302
TI  - Accidental occupational exposure to phytosanitary products: experience of the
      Poison Control Center in Marseille from 2008 to 2010.
AB  - To gain better insight into the problem of accidental occupational exposure to
      phytosanitary products, a retrospective study of experience at the Poison Control
      Center in Marseille, France, was conducted for the period between January 1,
      2008, and December 31, 2010. A 129-case series was compiled. The study population
      was overwhelmingly male (83%), and the most common cause was insecticides (56.6%
      with a half pyrethrin and 21% organophosphate) and herbicides (26%). Although
      various exposure routes were observed, the most common were inhalation (43%) and
      skin contact (34%). The symptoms were mainly neurologic, digestive, and/or
      cutaneous. The severity of poisoning was generally mild, with no deaths or
      sequels. Only 5% of cases required hospitalization.

PMID- 23540303
TI  - Exercise habits and tobacco use among male Latino farmworkers.
AB  - Migrant farmworkers risk occupational injury and are at risk for developing
      chronic health conditions. Exercise may enhance health and help to reduce the
      risk of occupational injury and/or reduce the risk of developing a chronic health
      condition. Little is known, however, about the exercise habits of Latino migrant
      farmworkers. Male Latino migrant farmworkers completed an exercise and health
      habits questionnaire at health screening clinics. One hundred fifty-three (58.2%)
      subjects reported exercising during the week. There was no difference in age
      between those who reported exercising and those who did not (p = .78). Only 42
      (16%) of all workers reported exercising for 3 or more hours a week. Seventeen
      percent of the subjects reported smoking and almost 10% reported chewing tobacco.
      A majority of subjects do not meet the Centers for Disease Control and Prevention
      (CDC) exercise guidelines. Tobacco use is highest among individuals who do not
      exercise. These findings suggest the need for health education interventions for
      this population. Additional studies are warranted to understand exercise and
      health habits of this population.

PMID- 23540304
TI  - Is gender a risk factor for pesticide intoxications among farmers in Bolivia? A
      cross-sectional study.
AB  - This study compares gender differences regarding knowledge, practice, and
      symptoms of intoxication when handling pesticides in farming. Data were gathered
      in La Paz County, Bolivia, in 2008 and 2009. Poor knowledge on safe handling,
      hazardous working practices, and use of very toxic pesticides were seen. Being a
      female and having a low educational level were risk factors for "poor knowledge
      on pesticides" and a "risky behavior when handling pesticides." Females reported
      more symptoms of intoxication. The gender differences on knowledge and handling
      practices might explain why females report more symptoms. To minimize this gap,
      education and agricultural services should be made more accessible to female
      farmers in Bolivia.

PMID- 23540305
TI  - Hazards for farmers with disabilities: working in cold environments.
AB  - In consequence of working in cold environments, agricultural workers may be
      exposed to higher risk of cold-related injuries, compared with the general
      population. These injuries can include tissue damage due to the exposure to
      subfreezing temperatures, more generalized symptoms caused by hypothermia, and
      secondary injuries caused by impaired performance. Risk of cold injury is
      increased for older workers and for those with disabling health conditions, both
      of which occur in above-average numbers in agriculture. Based on a selective
      review of the literature and case studies assembled by Purdue's Breaking New
      Ground Resource Center, an overview is presented of the mechanisms and symptoms
      of cold injuries, together with practical suggestions to help reduce risks of
      cold injuries for workers in agricultural settings. Special attention is given to
      potential risks to individuals with physical disabilities.

PMID- 23540306
TI  - Inhalation of phosphine gas following a fire associated with fumigation of
      processed pistachio nuts.
AB  - On December 10, 2009, a fumigation stack containing aluminum phosphide became
      soaked with rain water and caught fire at a pistachio processing plant in Kern
      County, California. Untrained plant personnel responding to the fire had exposure
      to pyrolysis by-products, particulates, and extinguisher ingredients. Ten workers
      taken for medical evaluation had respiratory and nonspecific systemic symptoms
      consistent with exposure to phosphine gas. Six of the 10 workers had respiratory
      distress, indicated by chest pain, shortness of breath, elevated respiratory
      rate, or decreased oxygen saturation. Recommendations are made for the management
      of similar illnesses and prevention of similar exposures.

PMID- 23540307
TI  - Aldicarb: a case series of watermelon-borne carbamate toxicity.
AB  - Improper use of pesticides on food plants can result in significant toxicity. In
      spite of regulations, enforcement, and prior episodes of poisonings, poisonings
      from misapplication of pesticides continues to occur. The objective of this study
      was to present a case series of toxicity resulting from ingestion of watermelon
      inappropriately treated with the carbamate insecticide aldicarb. A restrospective
      review of medical records, impounding the suspected watermelons, and chemical
      analysis of the watermelon samples using liquid chromatography and mass
      spectroscopy were carried out. Seven farm workers shared a watermelon and
      presented to a rural emergency department with symptoms of cholinergic poisoning.
      They were treated empirically with atropine and pralidoxime. The farmer denied
      use of insecticides other than rat poison on the watermelon patch. Chemical
      analyst verified aldicarb in the watermelon samples from the field, but none in
      control samples. Despite government regulations, application of restricted
      pesticides such as aldicarb continues to occur and cause significant poisonings.

PMID- 23540313
TI  - Advocacy for health: revisiting the role of health promotion.
AB  - ISSUE ADDRESSED: The importance of advocacy in protecting the population's
      health; and suggested strategies to advance an advocacy role. DISCUSSION: This
      article explores the concept of health advocacy, discusses an example of
      successful health advocacy within Australia, and outlines and addresses some of
      the barriers to advocacy. It aims to encourage discussion on advocacy's potential
      to improve the public's health. CONCLUSIONS: Many of the major successes of
      health promotion have been facilitated through the efforts of advocates. This
      article supports the proposition that advocacy is a fundamental instrument of
      health promotion practice and suggests strategies to apply these principles in
      practice.

PMID- 23540309
TI  - Examining palliative care team involvement in automatic consultations for
      children on extracorporeal life support in the pediatric intensive care unit.
AB  - BACKGROUND: Extracorporeal life support (ECLS) is an advanced form of life
      sustaining therapy that creates stressful dilemmas for families. In May 2009,
      Seattle Children's Hospital (SCH) implemented a policy to involve the Pediatric
      Advanced Care Team (PACT) in all ECLS cases through automatic referral.
      OBJECTIVE: Our aim was to describe PACT involvement in the context of automatic
      consultations for ECLS patients and their family members. METHODS: We
      retrospectively examined chart notes for 59 consecutive cases and used content
      analysis to identify themes and patterns. RESULTS: The degree of PACT involvement
      was related to three domains: prognostic uncertainty, medical complexity, and
      need for coordination of care with other services. Low PACT involvement was
      associated with cases with little prognostic uncertainty, little medical
      complexity, and minimal need for coordination of care. Medium PACT involvement
      was associated with two categories of cases: 1) those with a degree of medical
      complexity but little prognostic uncertainty; and 2) those that had a degree of
      prognostic uncertainty but little medical complexity. High PACT involvement had
      the greatest medical complexity and prognostic uncertainty, and also had those
      cases with a high need for coordination of care. CONCLUSIONS: We describe a
      framework for understanding the potential involvement of palliative care among
      patients receiving ECLS that explains how PACT organizes its efforts toward
      patients and families with the highest degree of need. Future studies should
      examine whether this approach is associated with improved patient and family
      outcomes.

PMID- 23540315
TI  - The Early Childhood Oral Health Program: promoting prevention and timely
      intervention of early childhood caries in NSW through shared care.
AB  - ISSUE ADDRESSED: Early childhood caries (ECC) continues to have high prevalence
      worldwide, despite being largely preventable. The Early Childhood Oral Health
      (ECOH) Program was established in New South Wales (NSW) using a model of shared
      responsibility for oral health, which involves a partnership between child health
      professionals, oral health professionals and parents of young children, to
      facilitate the primary prevention, early identification and early intervention of
      ECC. METHODS: An evaluation of the ECOH program was conducted, using mixed
      methods. Data were obtained through document review, surveys and interviews with
      program implementers, and analysis of the Information System for Oral Health
      (ISOH) database for public oral health services activity in NSW. RESULTS: Key
      achievements of the ECOH program include the establishment of governance
      mechanisms, policy, structures and responsibilities for implementation, support
      mechanisms for child health professionals, referral processes, communications
      resources, and the delivery of training. Parents receive oral health information,
      education and support through written resources and contact with child health
      professionals. Child and family health nurses interviewed reported routinely
      incorporating oral health promotion and early identification for ECC into their
      practices. The referral rate to public oral health services for children under
      five years of age by community health professionals has increased steadily since
      the program began, with the rate in 2009 five times higher than in 2007.
      CONCLUSIONS: Models of shared responsibility for oral health between parents,
      child health professionals and oral health professionals can facilitate primary
      prevention and early intervention for ECC.

PMID- 23540316
TI  - Participant perceptions of a community-based lifestyle intervention: the CHIP.
AB  - ISSUE ADDRESSED: The Coronary Health Improvement Project (CHIP) is a community
      based educational initiative designed to improve cardiovascular fitness and other
      health indicators associated with common, lifestyle-related health disorders in
      developed societies. Evaluations of the CHIP since the late 1990s, though
      yielding positive statistical results for change in participant physical health
      indicators, have not included qualitative assessments of the CHIP experience from
      the perspectives of CHIP participants. METHODS: Data were obtained using a mixed
      methods survey design via a questionnaire completed by 79 respondents (71%
      female) who had participated in Australian CHIP programs. Responses were analysed
      using descriptive statistics and thematic analysis. RESULTS: Participants
      commonly undertook the CHIP to fulfil their lifestyle and health aspirations and
      to target specific health conditions. Improved diet, enhanced exercise and weight
      loss were the most commonly reported benefits. Participation in the CHIP involves
      a process of conviction (involving risks and motivation), connection (involving
      support and reinforcement), challenge (involving control and struggle) and change
      (involving more and less). CONCLUSION: This study offers a model of a change
      process generated from the perspectives of participants of the CHIP in Australia.
      Not all participants found CHIP lifestyle recommendations straightforward to
      adopt, as some encountered resistance from within themselves or from family and
      friends.

PMID- 23540317
TI  - The implementation of a pilot playground markings project in four Australian
      primary schools.
AB  - ISSUE ADDRESSED: Increasing childhood overweight and obesity rates need
      strategies that promote and engage children in more physical activity and school
      is one setting for this. This pilot project aimed to determine if coloured
      playground markings are an effective strategy, in the Australian context, to
      increase students' physical activity during school break times in primary
      schools. METHODS: Four schools participated, two as intervention schools and two
      as control schools. A combination of data collection methods were used, including
      accelerometers on students, playground observations and a teacher survey.
      RESULTS: The accelerometer and observation data did not show an improvement in
      the physical activity levels of the intervention students compared to the control
      students. The teacher survey was positive in all aspects of the project
      implementation. Observations suggest that most students were active in large
      grass areas rather than around the playground markings. CONCLUSION: Based on our
      data, it is unclear whether playground markings are an effective intervention to
      increase physical activity in the school setting. The amount of playing space
      available appears to influence the use of the playground markings.

PMID- 23540318
TI  - Can social and community service organisations embrace tobacco control for their
      disadvantaged clients?
AB  - ISSUE ADDRESSED: High smoking rates among the disadvantaged lead to inequalities
      in health, quality-of-life and financial well-being. Non-government social and
      community service organisations (SCSO) are a promising setting for tobacco
      control interventions targeting disadvantaged smokers. METHODS: Financial grants
      were provided to twenty SCSO in New South Wales to support multi-level changes in
      service culture, smoking related policies and cessation support between 2007 and
      2009. Evaluation was conducted using a mixed-methods approach that included key
      informant interviews, document analysis and staff survey data. RESULTS: SCSO
      working with disadvantaged clients can feasibly implement tobacco control
      activities, including smoking-related policy changes and cessation support.
      Tobacco control activities were generally acceptable to staff and clients, and
      staff pessimism regarding their clients' ability to quit reduced, as did the
      acceptability of staff smoking with their clients. Improvements in levels of
      organisational support for cessation training and resources, smoking policies and
      provision of free nicotine replacement therapy (NRT) were reported. Within mental
      health SCSO there was a positive response from staff to cessation support,
      financial benefits of quitting and the role of NRT. CONCLUSIONS: The evaluation
      pointed to the acceptability and feasibility of engaging disadvantaged smokers by
      SCSO, and that tobacco policy and attitude changes can be achieved by small
      investments, such as grant programs.

PMID- 23540319
TI  - Evaluation of a sexual health and blood-borne virus health education website for
      youth.
AB  - ISSUE ADDRESSED: The 'Get the Facts' website, aimed at Western Australian (WA)
      youth aged 14 -17 years, provides information about sexual health, blood-borne
      viruses and sexual relationships, and how to access appropriate health services.
      It was developed as one component of a comprehensive sexually transmitted
      infection (STI) prevention and control program implemented within Western
      Australia. METHODS: An evaluation was undertaken to assess how the website might
      be improved and be more effectively marketed to its target audience. Website
      usage data, on-line survey responses and qualitative data from focus group
      testing of the website were collected and analysed. RESULTS: Website visitors
      were from 194 countries, with the majority being Australian (65%) and 27% of
      Australian visitors being from WA. Website usage patterns indicated that the site
      was of greater relevance to WA than other visitors. An estimated 5% of 14-17 year
      old WA residents had visited the site in 2010. Online survey and focus group data
      indicated that the website provides sexual health and bloodborne virus
      information that is relevant to young people and in a format that they find
      acceptable and accessible. CONCLUSIONS: The 'Get the Facts' website appeals to
      its target audience and provides them with relevant information. The challenge is
      to improve its promotion so it reaches its full potential WA youth audience.

PMID- 23540320
TI  - Active, healthy cities--how does population physical activity vary between
      Australian cities?
AB  - ISSUE ADDRESSED: Despite recognition that urban infrastructure influences
      physical activity, there have been no comparisons between Australian city-level
      patterns of physical activity. This study ranked Australian cities in terms of
      adults' participation in leisure-time physical activity and examined city-level
      variations in activity trends between 2001 and 2009. METHODS: Data on
      participation in leisure-time physical activity in adults (>=15 years) between
      2001 and 2009 were obtained from the Exercise Recreation and Sport Survey
      (ERASS), a computer-assisted telephone interview conducted to collect population
      level sport participation information by the Australian Sports Commission. Data
      were analysed for respondents residing in the eight capital cities of Australia.
      The prevalence of meeting recommended 'health-enhancing physical activity' (HEPA)
      and levels of walking were calculated by age, gender and survey year. Multiple
      linear logistic regression analyses were used to compare cities. RESULTS: Pooled
      data from 174,323 adults across years showed that Melbourne, Brisbane, Perth and
      Canberra residents were significantly more active than Sydney, Adelaide and
      Hobart residents in terms of HEPA. Hobart, Perth and Melbourne residents were
      significantly more likely to walk >=5 sessions a week compared with their
      counterparts in other cities. HEPA and walking increased across most cities
      between 2001 and 2009. CONCLUSION: There are significant differences between
      Australian cities in physical activity and walking levels, over and above
      differences attributable to age, gender or educational levels. While this may be
      due to infrastructure differences, comparative information on indicators of the
      built environment and transport infrastructure are not available.

PMID- 23540321
TI  - Occupational sitting: practitioner perceptions of health risks, intervention
      strategies and influences.
AB  - ISSUE ADDRESSED: Workplace practitioners are well placed to provide practical
      insights on sedentary behaviour issues in the workplace. This study consulted
      occupational health and safety (OHS) practitioners, examining their perceptions
      of sedentary health risks and views on strategies and influences to reduce and
      break prolonged occupational sitting. METHODS: Three focus groups were conducted
      with convenience samples of OHS practitioners (n=34; 6 men; 46.4 +/- 9.6 years)
      attending an Australian national conference in November 2010. Open-ended
      questions concerning health risks, sitting reduction strategies and influences
      were posed by lead researchers and practitioners invited to express opinions,
      viewpoints and experiences. Audio-recordings and summary notes of focus group
      discussions were reviewed by researchers to identify key response themes.
      RESULTS: OHS practitioners were well informed about the chronic disease and
      musculoskeletal risks associated with prolonged occupational sitting, but noted
      the importance of not replacing one workplace health issue (too much sitting)
      with another (too much standing). Ideas for strategies were diverse and explored
      the dichotomy between providing choices for employees to stand and move more
      (e.g. sit-stand desks), as opposed to obligating change through adapting job and
      office design (e.g. centralising printers and scanners). Productivity concerns
      were cited as a major influence for change. OHS practitioners also highlighted
      the value of using cross-disciplinary expertise to bridge the gap between
      research and practice. CONCLUSIONS: This study identified that OHS practitioners
      in Australia have a good understanding of the risks of prolonged occupational
      sitting and potential strategies to manage these risks.

PMID- 23540322
TI  - Prevalence and socio-demographic distribution of eating, physical activity and
      sedentary behaviours among Australian adolescents.
AB  - ISSUE ADDRESSED: To examine the prevalence and socio-demographic distribution of
      adherence to national dietary and physical activity recommendations among
      Australian secondary school students. METHODS: Cross-sectional survey of 12,188
      students in Years 8 to 11 (aged 12-17 years). Students' self-reported eating,
      physical activity and sedentary behaviours were assessed using validated
      instruments administered via an online questionnaire. RESULTS: Less than one
      quarter of students (24%) reported meeting the daily requirement of at least four
      serves of vegetables, while 41% reported consuming the recommended three or more
      daily serves of fruit. Just 15% of students reported engaging in at least 60
      minutes of moderate-to-vigorous activity every day, and only one in five students
      met the recommendation of spending no more than two hours per day in small screen
      recreation. Males were performing better than females in terms of fruit intake
      and physical activity, but worse in relation to frequency of consumption of
      sugary drinks and fast food, and time spent using electronic media. The
      proportion of students meeting fruit and vegetable recommendations declined with
      advancing year level, while lower socio-economic position (SEP) students were
      faring less well than those from high SEP neighbourhoods, particularly with
      regards to healthy eating. CONCLUSIONS: There is considerable scope for improving
      young people's health behaviours in line with national dietary and physical
      activity recommendations.

PMID- 23540323
TI  - The Alcohol Awareness project: community education and brief intervention in an
      urban Aboriginal setting.
AB  - ISSUE ADDRESSED: Although many Aboriginal Australians live in cities, minimal
      research has addressed community-based approaches to reduce alcohol problems in
      that setting. METHODS: We conducted a pilot study of community-based education
      and brief intervention. Existing Aboriginal community-based groups in an urban
      region were offered interactive education sessions with Aboriginal facilitators.
      The session was based around a World Health Organization brief intervention, with
      posters as visual aids. Before education, participants completed the Alcohol Use
      Disorders Identification Test (AUDIT) and questions on potential barriers to
      treatment access. After the session, feedback on AUDIT score and one- on- one
      brief intervention were offered. RESULTS: Over 12 months, eight sessions were
      conducted and 58 individuals participated. The groups reached individuals with
      potential need for assistance: although 29.8% of the 47 questionnaire respondents
      were non-drinkers, 44.7% had an AUDIT score (of 8+) suggesting an alcohol
      problem, and 51.5% of drinkers reported 5+ (non-standardised) drinks per
      occasion. Participants showed considerable interest in the resources and most
      actively participated. All appeared unaware of recommended drinking limits, or of
      newer treatment options such as home detoxification or relapse prevention
      medicines. Participants were interested to receive their AUDIT score but not one
      on- one intervention. Potential treatment access barriers were described.
      CONCLUSIONS: Interactive group education and feedback of AUDIT score is labour
      intensive but promoted thoughtful discussion on drinking. Methods to empower and
      support urban Aboriginal communities to tackle drinking problems need further
      exploration.

PMID- 23540324
TI  - Youth and Relationship Networks (YARNS): mobilising communities for sexual
      health.
AB  - ISSUE ADDRESSED: Community participation is vital if sexual health disadvantage
      among Aboriginal and Torres Strait Islander young people is to be addressed, yet
      there is a paucity of literature examining this issue. METHODS: The development,
      nature and impact of a community participation strategy for sexual health,
      implemented in two North Queensland sites, provided the opportunity for a
      systematic study, using qualitative and grounded theory analytic methods, of the
      factors that enable and constrain community participation in this context. A
      total of 30 people participated, in individual interviews and focus groups.
      RESULTS: The community participation strategy was fundamental to the development
      of culturally and community congruent sexual health initiatives. There were also
      signs of a changing discourse in community around sexual health. Factors that
      enabled effective community participation involved individual attributes,
      structured group processes, organisational support, empowering external
      relationships, a culturally sensitive strategy and enhanced health and wellbeing.
      CONCLUSION: The model developed here identifies factors that enable community
      participation and mobilisation, thus providing a valuable tool for health
      practitioners seeking to plan and evaluate strategies that address entrenched
      disadvantage in Aboriginal and Torres Strait Islander populations.

PMID- 23540325
TI  - Specific issues, exact locations: case study of a community mapping project to
      improve safety in a disadvantaged community.
AB  - ISSUE ADDRESSED: Safety is a health issue and a significant concern in
      disadvantaged communities. This paper describes an example of community-initiated
      action to address perceptions of fear and safety in a suburb in south-west Sydney
      which led to the development of a local, community-driven research project.
      METHODS: As a first step in developing community capacity to take action on
      issues of safety, a joint resident-agency group implemented a community safety
      mapping project to identify the extent of safety issues in the community and
      their exact geographical location. Two aerial maps of the suburb, measuring one
      metre by two metres, were placed on display at different locations for four
      months. Residents used coloured stickers to identify specific issues and exact
      locations where crime and safety were a concern. RESULTS: Residents identified
      294 specific safety issues in the suburb, 41.9% (n=123) associated with public
      infrastructure, such as poor lighting and pathways, and 31.9% (n=94) associated
      with drug-related issues such as drug activity and discarded syringes.
      CONCLUSIONS: Good health promotion practice reflects community need. In a very
      practical sense, this project responded to community calls for action by mapping
      resident knowledge on specific safety issues and exact locations and presenting
      these maps to local decision makers for further action.

PMID- 23540326
TI  - Do health behaviours cluster in a working population in New Zealand?
AB  - ISSUE ADDRESSED: This study examines whether adhering to healthy weight, physical
      activity and fruit and vegetable recommendations lead to a cluster in a working
      population. METHODS: An online Health Risk Assessment (HRA) was administered to
      1,296 (36%) employees in nine organisations across New Zealand. Clustering was
      defined as the co-prevalence of behaviours above that which was expected by the
      laws of probability. RESULTS: Less than half the participants met physical
      activity guidelines (44.5%) or maintained a healthy weight (46.7%), and 29.4%
      consumed five or more servings of fruit and vegetables per day. Just 3.8% of
      participants met all three recommendations, compared to an expected prevalence of
      7.6%. There was no clustering of health behaviours, with no difference between
      expected and observed prevalence (with an observed/expected (O/E) ratio between
      0.68-0.93). CONCLUSION: Few people adhere to two or more simple public health
      messages recommended to reduce risk of chronic disease.

PMID- 23540327
TI  - Evidence-based practice?

PMID- 23540328
TI  - Community-based primary prevention programs decrease the rate of metabolic
      syndrome among socioeconomically disadvantaged women.
AB  - BACKGROUND: Metabolic Syndrome (MetSyn) is one of the strongest predictors of
      type 2 diabetes (DM2) and cardiovascular disease (CVD). It is associated with a 4
      to 10-fold increased risk of DM2 and a 2- to 3-fold increased risk of CVD. Low
      income and minority women have some of the highest rates of MetSyn. This study
      examines the effect of a unique, community based, primary prevention program on
      the rates of MetSyn and health habits. METHODS: Sixty-four low income and
      minority women were enrolled in the HAPPY (Health Awareness and Primary
      Prevention in Your neighborhood) Heart Program in an eastern suburb of Boston.
      Over these 2 years, patients were evaluated by an interdisciplinary medical team:
      their primary physician, cardiologist, nutritionist, physical therapist, and
      health coach. The rate of MetSyn was measured at baseline, year 1, and year 2.
      Comparisons were made either using the paired t test for normally distributed
      variables or the Wilcoxon Sign test for non-normal variables. RESULTS: The rate
      of MetSyn fell from 64.7% at baseline to 34.9% at year 1 (p=0.01) and 28.2% at
      year 2 (p<0.001). This was driven by increases in high-density lipoprotein (HDL
      C) (p<0.001) and decreases in blood pressure (p=0.05). Fasting blood glucose
      trended down, but the hemoglobin A1c (HbA1c) reached significance (decreasing
      from 6 to 5.8, p<0.01). Nutrition and exercise habits trended toward improvement.
      There were significant decreases in anxiety (p<0.001), depression (p=0.006) and
      stress (p=0.002). CONCLUSION: This lifestyle intervention program is effective at
      decreasing MetSyn in a socioeconomically disadvantaged, largely minority, female
      population. This program also decreases anxiety, stress, and depression among
      participants.

PMID- 23540329
TI  - Transforming women's oral-systemic health through discovery, development, and
      delivery.
AB  - BACKGROUND: Oral-systemic etiologies solely or disproportionally affect women's
      health; however, little communication between and among disciplines occurs.
      METHODS: To bridge this gap, an innovative conference, "Transforming Women's
      Health: Discovery, Development, and Delivery," was held in Tampa, Florida. The
      conference aimed to address complex oral-systemic women's health issues by
      bringing together researchers, providers, and policy experts in dentistry,
      medicine, nursing, public health, and allied health professions. The program was
      structured by three organizational themes: (a) discovery (i.e., oral-systemic
      research specific to women's health issues); (b) development (i.e., translation
      of oral-systemic research to practice); and (c) delivery (i.e., collaborative
      practice). RESULTS: Issues discussed during conference proceedings include oral
      system health in children, pregnant women, and older women, and cardiovascular
      disease and human papillomavirus (HPV) as oral-systemic health issues. Team and
      system-based approaches to reducing disciplinary-specific research, developing
      cross-disciplinary strategies and methods for improving women's health, and the
      advantages of creating collaborative networks, as well as effective communication
      practices with patients, were addressed. CONCLUSION: Based on findings from this
      innovative conference, it is clear that creating a transdisciplinary paradigm of
      research and practice may be the most effective vehicle for addressing oral
      systemic health issues.

PMID- 23540330
TI  - Tunable nanowire patterning using standing surface acoustic waves.
AB  - Patterning of nanowires in a controllable, tunable manner is important for the
      fabrication of functional nanodevices. Here we present a simple approach for
      tunable nanowire patterning using standing surface acoustic waves (SSAW). This
      technique allows for the construction of large-scale nanowire arrays with well
      controlled patterning geometry and spacing within 5 s. In this approach, SSAWs
      were generated by interdigital transducers, which induced a periodic alternating
      current (ac) electric field on the piezoelectric substrate and consequently
      patterned metallic nanowires in suspension. The patterns could be deposited onto
      the substrate after the liquid evaporated. By controlling the distribution of the
      SSAW field, metallic nanowires were assembled into different patterns including
      parallel and perpendicular arrays. The spacing of the nanowire arrays could be
      tuned by controlling the frequency of the surface acoustic waves. Additionally,
      we observed 3D spark-shaped nanowire patterns in the SSAW field. The SSAW-based
      nanowire-patterning technique presented here possesses several advantages over
      alternative patterning approaches, including high versatility, tunability, and
      efficiency, making it promising for device applications.

PMID- 23540331
TI  - How does Listeria monocytogenes combat acid conditions?
AB  - Listeria monocytogenes, a major foodborne pathogen, possesses a number of
      mechanisms that enable it to combat the challenges posed by acidic environments,
      such as that of acidic foods and the gastrointestinal tract. One mechanism
      employed by L. monocytogenes for survival at low pH is the adaptive acid
      tolerance response (ATR) in which a short adaptive period at a nonlethal pH
      induces metabolic changes that allow the organism to survive a lethal pH.
      Overcoming acid conditions by L. monocytogenes involves a variety of regulatory
      responses, including the LisRK 2-component regulatory system, the SOS response,
      components of the sigma(B) regulon, changes in membrane fluidity, the F0F1-ATPase
      proton pump, and at least 2 enzymatic systems that regulate internal hydrogen ion
      concentration (glutamate decarboxylase and arginine deiminase). It is not clear
      if these mechanisms exert their protective effects separately or in concert, but
      it is probable that these mechanisms overlap. Studies using mutants indicate that
      the glutamate decarboxylase system can protect L. monocytogenes when the organism
      is present in acidic juices, yogurt, salad dressing, mayonnaise, and modified CO2
      atmospheres. The glutamate decarboxylase system also has a role in protecting L.
      monocytogenes against the acidic environment of the stomach. There is a need to
      study other acid resistance mechanisms of L. monocytogenes to determine their
      effectiveness in protecting the organism in acidic foods or during transit
      through the acid stomach.

PMID- 23540332
TI  - Is the GAIN Act a turning point in new antibiotic discovery?
AB  - The United States GAIN (Generating Antibiotic Incentives Now) Act is a call to
      action for new antibiotic discovery and development that arises from a ground
      swell of concern over declining activity in this therapeutic area in the
      pharmaceutical sector. The GAIN Act aims to provide economic incentives for
      antibiotic drug discovery in the form of market exclusivity and accelerated drug
      approval processes. The legislation comes on the heels of nearly two decades of
      failure using the tools of modern drug discovery to find new antibiotic drugs.
      The lessons of failure are examined herein as are the prospects for a renewed
      effort in antibiotic drug discovery and development stimulated by new investments
      in both the public and private sector.

PMID- 23540333
TI  - Detection of viable but nonculturable Escherichia coli O157:H7 using propidium
      monoazide treatments and qPCR.
AB  - Escherichia coli O157:H7 can enter into a viable but nonculturable (VBNC) state
      under stress conditions. The aims of the present study were to examine the
      influences of environmental factors on the survivability and culturability of E.
      coli O157:H7 and to develop an approach for accurate detection of VBNC E. coli
      O157:H7. The E. coli O157:H7 strain ATCC 6589 was inoculated into 3 induction
      microcosm models: (i) Luria-Bertani broth, (ii) sterilized tap water, and (iii)
      sterilized physiological saline solution. Our results showed that low temperature
      and nutritional starvation significantly impacted on the survivability of E. coli
      O157:H7 cells and that the in-vitro-induced VBNC cells were capable of
      resuscitating under normal temperature and appropriate nutrients. We tested the
      effectiveness of an approach combining propidium monoazide (PMA) treatment with
      real-time polymerase chain reaction (PMA-qPCR) for accurate quantification of
      total, viable, dead, and VBNC cells under different induction microcosm models.
      Our results indicated different threshold cycle (Ct) values for PMA-treated cells
      and untreated cells (DeltaCt = 4.97, 4.29, and 3.30 for Luria-Bertani broth,
      sterilized tap water, and sterilized physiological saline solution,
      respectively). We determined the quantification limit of this PMA-qPCR approach
      to be 1 * 10(2) cells.mL(-1), providing sufficient sensitivity for detection of
      VBNC E. coli O157:H7 cells to no less than 100 cells.mL(-1). This study clearly
      demonstrated the feasibility and effectiveness of using PMA-qPCR to accurately
      quantify E. coli O157:H7 in a VBNC state.

PMID- 23540335
TI  - Factors affecting the occurrence of Escherichia coli O157 contamination in
      irrigation ponds on produce farms in the Suwannee River Watershed.
AB  - Outbreaks of enteritis caused by Escherichia coli O157 associated with fresh
      produce have resulted in questions about the safety of irrigation water; however,
      associated risks have not been systematically evaluated. In this study, the
      occurrence and distribution of the human pathogen E. coli O157 from vegetable
      irrigation ponds within the Suwannee River Watershed in Georgia were
      investigated, and the relationship to environmental factors was analyzed. Surface
      and subsurface water samples were collected monthly from 10 vegetable irrigation
      ponds from March 2011 to February 2012. Escherichia coli O157 was isolated from
      enriched filtrates on CHROMagar and sorbitol MacConkey agar media and confirmed
      by an agglutination test. Presence of virulence genes stx1, stx2 , and eae was
      tested by polymerase chain reaction. In addition, 27 environmental variables of
      the sampled ponds were measured. Denaturing gradient gel electrophoresis was
      conducted for the analysis of bacterial communities in the water samples.
      Biserial correlation coefficients were calculated to evaluate the log10 colony
      forming unit per millilitre correlations between the environmental factors and
      the occurrence of E. coli O157. Stepwise and canonical discriminant analyses were
      used to determine the factors that were associated with the presence and absence
      of E. coli O157 in water samples. All 10 ponds were positive for E. coli O157
      some of the time, mainly in summer and fall of 2011. The temporal distribution of
      this bacterium differed among the 10 ponds. Temperature, rainfall, populations of
      fecal coliform, and culturable bacteria were positively correlated with the
      occurrence of E. coli O157 (P < 0.05), while the total nitrogen concentration,
      oxidation-reduction potential, and dissolved oxygen concentration were negatively
      correlated with the occurrence of this pathogen (P < 0.05). Temperature and
      rainfall were the most important factors contributing to the discrimination
      between samples with and without E. coli O157, followed by bacterial diversity
      and culturable bacteria population density. Bacterial numbers and diversity,
      including fecal coliforms and E. coli O157, increased after rainfall (and
      possibly runoff from pond margins) in periods with relatively high temperatures,
      suggesting that prevention of runoff may be important to minimize the risk of
      enteric pathogens in irrigation ponds.

PMID- 23540334
TI  - Rhizosphere bacteria of Costularia spp. from ultramafic soils in New Caledonia:
      diversity, tolerance to extreme edaphic conditions, and role in plant growth and
      mineral nutrition.
AB  - Rhizosphere bacteria were isolated from Costularia spp., pioneer sedges from
      ultramafic soils in New Caledonia, which is a hotspot of biodiversity in the
      South Pacific. Genus identification, ability to tolerate edaphic constraints, and
      plant-growth-promoting (PGP) properties were analysed. We found that 10(5) colony
      forming units per gram of root were dominated by Proteobacteria (69%) and
      comprised 21 genera, including Burkholderia (28%), Curtobacterium (15%),
      Bradyrhizobium (9%), Sphingomonas (8%), Rhizobium (7%), and Bacillus (5%). High
      proportions of bacteria tolerated many elements of the extreme edaphic
      conditions: 82% tolerated 100 MUmol.L(-1) chromium, 70% 1 mmol.L(-1) nickel, 63%
      10 mmol.L(-1) manganese, 24% 1 mmol.L(-1) cobalt, and 42% an unbalanced
      calcium/magnesium ratio (1/16). These strains also exhibited multiple PGP
      properties, including the ability to produce ammonia (65%), indole-3-acetic acid
      (60%), siderophores (52%), and 1-aminocyclopropane-1-carboxylate (ACC) deaminase
      (39%); as well as the capacity to solubilize phosphates (19%). The best
      performing strains were inoculated with Sorghum sp. grown on ultramafic
      substrate. Three strains significantly enhanced the shoot biomass by up to 33%.
      The most successful strains influenced plant nutrition through the mobilization
      of metals in roots and a reduction of metal transfer to shoots. These results
      suggest a key role of these bacteria in plant growth, nutrition, and adaptation
      to the ultramafic constraints.

PMID- 23540336
TI  - Biofilms from a Brazilian water distribution system include filamentous fungi.
AB  - Filamentous fungi in drinking water can block water pipes, can cause organoleptic
      biodeterioration, and are a source of pathogens. There are increasing reports of
      the involvement of the organisms in biofilms. This present study describes a
      sampling device that can be inserted directly into pipes within water
      distribution systems, allowing biofilm formation in situ. Calcofluor White M2R
      staining and fluorescent in situ hybridization with morphological analyses using
      epifluorescent microscopy were used to analyse biofilms for filamentous fungi,
      permitting direct observation of the fungi. DAPI (4',6-diamidino-2-phenylindole)
      was applied to detect bacteria. Filamentous fungi were detected in biofilms after
      6 months on coupons exposed to raw water, decanted water and at the entrance of
      the water distribution system. Algae, yeast, and bacteria were also observed. The
      role of filamentous fungi requires further investigations.

PMID- 23540337
TI  - Impact of arachidonic acid enrichment of live rotifer prey on bacterial
      communities in rotifer and larval fish cultures.
AB  - Rotifers (Brachionus plicatilis), commonly used at first feeding in commercial
      fish hatcheries, carry a large bacteria load. Because they are relatively poor in
      essential fatty acids, it is common practice to enrich them with fatty acids,
      including arachidonic acid (AA). This study aims to determine whether prey
      enrichment with AA may act as a prebiotic and modify the microbial community
      composition either in AA-enriched rotifer cultures or in larval-rearing water
      using winter flounder (Pseudopleuronectes americanus) as a larval fish model. AA
      enrichment modified the bacterial community composition in both the rotifer
      culture tanks and the larval-rearing tanks. We observed an increase in the number
      of cultivable bacteria on TCBS (thiosulfate-citrate-bile salts-sucrose) agar,
      used as a proxy for the abundance of Vibrio sp. The results suggest that AA may
      also play an indirect role in larval health.

PMID- 23540338
TI  - Variation in adhesion and germ tube formation of oral Candida using Egyptian
      propolis.
AB  - Adhesion of Candida cells to surfaces is considered the first step in
      colonization. Some natural products, such as propolis, could be used to block
      cell adhesion and therefore preventing colonization. In this study, Egyptian
      propolis ethanol extract concentrations in the range of 25 to 125 ng/MUL were
      used to inhibit the adhesion of oral Candida. The exopolysaccharides showed a 2.5
      fold decrease, while the surface-bound exopolysaccharides showed only about 1.15
      fold decrease. On the other hand, surface-bound proteins decreased by 7.5-fold
      upon the addition of 75 ng/MUL propolis. The inhibition of adhesion was detected
      by scanning electron microscopy. The non-slip incubation assay showed a
      significant decrease in germ tube formation (GTF) compared with an increase upon
      the addition of fetal bovine serum and corn meal, both of which had a positive
      effect on GTF compared with a negative GTF effect when using propolis, suggesting
      that propolis could be considered a quorum-sensing molecule. The use of propolis
      would help in maintaining the cleanliness of dental fixtures and (or) treating
      recurrent candidiasis as a complementary and alternative treatment, especially in
      elders and immunocompromised patients.

PMID- 23540339
TI  - Detection of Ophiocordyceps sinensis in soil by quantitative real-time PCR.
AB  - Ophiocordyceps sinensis, one of the best known entomopathogenic fungi in
      traditional Chinese medicine, parasitizes larvae of the moth genus Thitarodes,
      which lives in soil tunnels. However, little is known about the spatial
      distribution of O. sinensis in the soil. We established a protocol for DNA
      extraction, purification, and quantification of O. sinensis in soil with
      quantitative real-time PCR targeting the internal transcribed spacer region. The
      method was assessed using 34 soil samples from Tibet. No inhibitory effects in
      purified soil DNA extracts were detected. The standard curve method for absolute
      DNA quantification generated crossing point values that were strongly and
      linearly correlated to the log10 of the initial amount of O. sinensis genomic DNA
      (r(2) = 0.999) over 7 orders of magnitude (4 * 10(1) to 4 * 10(7) fg). The
      amplification efficiency and y-intercept value of the standard curve were 1.953
      and 37.70, respectively. The amount of O. sinensis genomic DNA decreased with
      increasing soil depth and horizontal distance from a sclerotium (P < 0.05). Our
      protocol is rapid, specific, sensitive, and provides a powerful tool for
      quantification of O. sinensis from soil.

PMID- 23540340
TI  - Identification of fecal contamination sources in water using host-associated
      markers.
AB  - In British Columbia, Canada, drinking water is tested for total coliforms and
      Escherichia coli, but there is currently no routine follow-up testing to
      investigate fecal contamination sources in samples that test positive for
      indicator bacteria. Reliable microbial source tracking (MST) tools to rapidly
      test water samples for multiple fecal contamination markers simultaneously are
      currently lacking. The objectives of this study were (i) to develop a qualitative
      MST tool to identify fecal contamination from different host groups, and (ii) to
      evaluate the MST tool using water samples with evidence of fecal contamination.
      Singleplex and multiplex polymerase chain reaction (PCR) were used to test (i)
      water from polluted sites and (ii) raw and drinking water samples for presence of
      bacterial genetic markers associated with feces from humans, cattle, seagulls,
      pigs, chickens, and geese. The multiplex MST assay correctly identified suspected
      contamination sources in contaminated waterways, demonstrating that this test may
      have utility for heavily contaminated sites. Most raw and drinking water samples
      analyzed using singleplex PCR contained at least one host-associated marker.
      Singleplex PCR was capable of detecting host-associated markers in small sample
      volumes and is therefore a promising tool to further analyze water samples
      submitted for routine testing and provide information useful for water quality
      management.

PMID- 23540341
TI  - Pd-catalyzed direct coupling of indoles with carbon monoxide and alkynes:
      selective synthesis of linear alpha,beta-unsaturated ketones.
AB  - A new strategy is described for the direct coupling of indoles with CO and
      alkynes to generate alpha,beta-unsaturated ketones. This procedure, employing
      Xantphos and Pd(CH3CN)4(BF4)2, is attractive from both environmental and
      operational points of view and adds value to the method for the carbonylation of
      alkynes by using carbon nucleophiles and affording linear regioselectivity.

PMID- 23540342
TI  - Antileukemic properties of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors.
AB  - Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors
      that act on the mevalonate pathway and inhibit synthesis of cholesterol,
      geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP). In
      preclinical studies, these agents have been shown to inhibit proliferation,
      trigger apoptosis and promote cell differentiation of leukemia. Proposed
      mechanisms include cholesterol deprivation and inhibition of isoprenylation of
      important signaling molecules. Case reports and early clinical studies suggest a
      therapeutic potential for statins in acute myeloid leukemia (AML). In the other
      leukemias there are limited clinical data, but in vitro studies provide a strong
      rationale for future studies involving statins. The effects of statins on the
      immune system may lend these agents to a role in allogeneic stem cell transplant.
      While many of the studies are early, statins have the future potential to be
      integrated into conventional chemotherapy regimens with limited side effects.

PMID- 23540343
TI  - CD38 expression in CLL: a dynamic marker of prognosis.

PMID- 23540344
TI  - Chemoprevention for smoldering multiple myeloma: not ready for prime time.

PMID- 23540345
TI  - Revisiting treatment paradigms in high-risk smoldering multiple myeloma: out with
      the old, in with the new?

PMID- 23540347
TI  - In vitro and in vivo enhancement of chemoradiation using the oral PARP inhibitor
      ABT-888 in colorectal cancer cells.
AB  - PURPOSE: Poly(ADP-ribose) polymerase plays a critical role in the recognition and
      repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an
      orally available inhibitor of this enzyme. This study seeks to evaluate the use
      of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal
      carcinoma models. METHODS AND MATERIALS: RT clonogenic assays were performed on
      HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin
      with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at
      10% survival were analyzed. Synergism was assessed by isobologram analysis for
      combination therapies. gammaH2AX and neutral comet assays were performed to
      assess the effect of therapy on DSB formation/repair. In vivo assessments were
      made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was
      measured at a volume of 500 mm(3). RESULTS: Both lines were radiosensitized by
      ABT alone, and ABT further increased chemotherapy dose-modifying factors to the
      1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9).
      ABT treatment significantly increased DSB after RT (gammaH2AX, 69% vs 43%;
      P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT;
      11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for
      5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT.
      CONCLUSION: ABT-888 radiosensitizes at similar or higher levels compared with
      classic chemotherapies and acts synergistically with these chemotherapies to
      enhance RT effects. In vivo confirmation of these results indicates a potential
      role for combining its use with existing chemoradiation regimens.

PMID- 23540348
TI  - Increased subventricular zone radiation dose correlates with survival in
      glioblastoma patients after gross total resection.
AB  - PURPOSE: Neural progenitor cells in the subventricular zone (SVZ) have a
      controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating
      cells. The purpose of this study was to examine the relationship between
      radiation dose to the SVZ and survival in GBM patients. METHODS AND MATERIALS:
      The study included 116 patients with primary GBM treated at the Johns Hopkins
      Hospital between 2006 and 2009. All patients underwent surgical resection
      followed by adjuvant radiation therapy with intensity modulated radiation therapy
      (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral,
      and bilateral SVZs were contoured on treatment plans by use of coregistered
      magnetic resonance imaging and computed tomography. Multivariate Cox regression
      was used to examine the relationship between mean SVZ dose and progression-free
      survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance
      Status score, and extent of resection were used as covariates. The median age was
      58 years (range, 29-80 years). RESULTS: Of the patients, 12% underwent biopsy,
      53% had subtotal resection (STR), and 35% had gross total resection (GTR). The
      Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or
      greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean
      SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who
      underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated
      with a significantly improved PFS compared with patients who received less than
      40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence
      interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The
      subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater
      also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard
      ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found
      between SVZ radiation dose and PFS and OS among patients who underwent STR or
      biopsy. CONCLUSION: A mean radiation dose of 40 Gy or greater to the ipsilateral
      SVZ was associated with a significantly improved PFS and OS in patients with GBM
      after GTR.

PMID- 23540349
TI  - Patterns of failure in advanced stage diffuse large B-cell lymphoma patients
      after complete response to R-CHOP immunochemotherapy and the emerging role of
      consolidative radiation therapy.
AB  - PURPOSE: The role of consolidative radiation therapy (RT) after complete response
      (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and
      prednisone (R-CHOP) for stage III-IV diffuse large B-cell lymphoma (DLBCL)
      patients is unclear. We aimed to evaluate our institutional experience when
      consolidative RT is delivered to initial presenting sites or bulky sites in these
      patients. METHODS AND MATERIALS: We identified 211 histologically confirmed stage
      III-IV DLBCL patients who received R-CHOP from January 2000 to May 2012 at our
      institution. Patterns of failure for patients who achieved CR to R-CHOP were
      analyzed. Local control (LC), distant control (DC), progression-free survival
      (PFS), and overall survival (OS) were estimated using Kaplan-Meier method and
      compared between patients who received R-CHOP alone versus R-CHOP plus
      consolidative RT using the log-rank test. Multivariate analyses were also
      performed using Cox proportional hazards model. RESULTS: Detailed treatment
      records were available for 163 patients. After a median 6 cycles of R-CHOP, 110
      patients (67.5%) achieved CR and were entered for analysis. Fourteen patients
      (12.7%) received consolidative RT. After median follow-up of 32.9 months, 43.8%
      of patients who received R-CHOP alone failed at the initial sites with or without
      distant recurrence (DR), whereas isolated DR only occurred in 3.7% of these
      patients. Consolidative RT was associated with significantly improved LC (91.7%
      vs 48.8%), DC (92.9% vs 71.9%), PFS (85.1% vs 44.2%), and OS (92.3% vs 68.5%; all
      Ps<.0001) at 5 years compared with patients with R-CHOP alone. On multivariate
      analysis, consolidative RT and nonbulky disease were predictive of increased LC
      and PFS, whereas bone marrow involvement was associated with increased risk of DR
      and worse OS. Consolidative RT was also associated with marginal improved OS.
      CONCLUSIONS: Forty-four percent of patients with advanced stage DLBCL failed at
      initial presenting sites after achieving CR to R-CHOP. Incorporation of
      consolidative RT as part of upfront treatment in these patients was associated
      with improved LC, PFS, and a trend towards improved OS.

PMID- 23540350
TI  - Naltrexone and nalmefene: any meaningful difference?

PMID- 23540351
TI  - How to assess the role of transcranial magnetic stimulation in nicotine
      addiction.

PMID- 23540352
TI  - Gin and juice: modafinil tightens up the drinker's brain at rest.

PMID- 23540353
TI  - Differences in the repertoire, regulation and function of Toll-like Receptors and
      inflammasome-forming Nod-like Receptors between human and mouse.
AB  - Ilya Metchnikoff's use of starfish larvae to discover phagocytosis, and Bruno
      Lemaitre's and Jules Hoffmann's identification of host defence functions for
      Drosophila Toll provide compelling examples of the utility of model organisms for
      discovery of human innate immune pathways. Bruce Beutler's mapping of
      lipopolysaccharide non-responsiveness in C3H/HeJ mice to the Toll-like Receptor 4
      gene similarly highlights the power of the mouse as a model. Models have
      limitations however, and characterising the functional relevance of human innate
      immune responses not conserved in the mouse presents both a challenge and an
      opportunity. Here we review differences between human and mouse Toll-like
      Receptors and inflammasome-forming Nod-like Receptors in repertoire, regulation
      and function, highlighting the significance of these differences for human innate
      immunity. 

PMID- 23540354
TI  - An echogenic object in the left atrium: a consequence of end-stage renal disease?

PMID- 23540355
TI  - Stable isotope signatures for characterising the biological stability of
      landfilled municipal solid waste.
AB  - Stable isotopic signatures of landfill leachates are influenced by processes
      within municipal solid waste (MSW) landfills mainly depending on the
      aerobic/anaerobic phase of the landfill. We investigated the isotopic signatures
      of delta(13)C, delta(2)H and delta(18)O of different leachates from lab-scale
      experiments, lysimeter experiments and a landfill under in situ aeration. In the
      laboratory, columns filled with MSW of different age and reactivity were
      percolated under aerobic and anaerobic conditions. In landfill simulation
      reactors, waste of a 25year old landfill was kept under aerobic and anaerobic
      conditions. The lysimeter facility was filled with mechanically shredded fresh
      waste. After starting of the methane production the waste in the lysimeter
      containments was aerated in situ. Leachate and gas composition were monitored
      continuously. In addition the seepage water of an old landfill was collected and
      analysed periodically before and during an in situ aeration. We found significant
      differences in the delta(13)C-value of the dissolved inorganic carbon (delta(13)C
      DIC) of the leachate between aerobic and anaerobic waste material. During aerobic
      degradation, the signature of delta(13)C-DIC was mainly dependent on the isotopic
      composition of the organic matter in the waste, resulting in a delta(13)C-DIC of 
      200/00 to -250/00. The production of methane under anaerobic conditions caused an
      increase in delta(13)C-DIC up to values of +100/00 and higher depending on the
      actual reactivity of the MSW. During aeration of a landfill the aerobic
      degradation of the remaining organic matter caused a decrease to a delta(13)C-DIC
      of about -200/00. Therefore carbon isotope analysis in leachates and groundwater
      can be used for tracing the oxidation-reduction status of MSW landfills. Our
      results indicate that monitoring of stable isotopic signatures of landfill
      leachates over a longer time period (e.g. during in situ aeration) is a powerful
      and cost-effective tool for characterising the biodegradability and stability of
      the organic matter in landfilled municipal solid waste and can be used for
      monitoring the progress of in situ aeration. 

PMID- 23540356
TI  - Biotests for environmental quality assessment of composted sewage sludge.
AB  - The quality of sewage sludge-based products, such as composts and growth media,
      is affected by the contamination of sewage sludge with, potentially, hundreds of
      different substances. Therefore, it is difficult to achieve the reliable
      environmental quality assessment of sewage sludge-based products solely based on
      chemical analysis. In the present work, we demonstrate the use of the kinetic
      luminescent bacteria test (ISO 21338) to evaluate acute toxicity and the
      VitotoxTM test to monitor genotoxicity of sewage sludge and composted sewages
      sludge. In addition, endocrine-disrupting and dioxin-like activity was studied
      using yeast-cell-based assays. The relative contribution of industrial waste
      water treated at the Waste Water Treatment Plants led to elevated concentrations
      of polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and
      polychlorinated dibenzo-p-dioxins and -furans (PCDD/F) in sewage sludge. The
      effect of elevated amounts of organic contaminants could also be identified with
      biotests able to demonstrate higher acute toxicity, genotoxicity, and potential
      for endocrine-disruptive properties. Additional extraction steps in kinetic
      luminescent bacteria test with DMSO and hexane increased the level of toxicity
      detected. Composting in a pilot-scale efficiently reduced the amounts of linear
      alkylbenzensulphonates (LASs), nonylphenols and nonylphenolethoxylates (NPE/NPs)
      and PAH with relative removal efficiencies of 84%, 61% and 56%. In addition,
      decrease in acute toxicity, genotoxicity and endocrorine-disrupting and dioxin
      like activity during composting could be detected. However, the biotests did have
      limitations in accessing the ecotoxicity of test media rich with organic matter,
      such as sewage sludge and compost, and effects of sample characteristics on
      biotest organisms must be acknowledged. The compost matrix itself, however, which
      contained a high amount of nutrients, bark, and peat, reduced the sensitivity of
      the genotoxicity tests and yeast bioreporter assays.

PMID- 23540357
TI  - Anaerobic co-digestion of livestock and vegetable processing wastes: fibre
      degradation and digestate stability.
AB  - Anaerobic digestion of livestock wastes (swine manure (SM) and poultry litter
      (PL)) and vegetable processing wastes (VPW) mixtures was evaluated in terms of
      methane yield, volatile solids removal and lignocellulosic material degradation.
      Batch experiments were performed with 2% VS (volatile solids) to ensure complete
      conversion of TVFAs (total volatile fatty acids) and to avoid ammonia inhibition.
      Experimental methane yields obtained for the mixtures resulted in higher values
      than those obtained from the sum of the methane yields from the individual
      components. VPW addition to livestock wastes before anaerobic digestion also
      resulted in improved VS elimination. In SM-VPW co-digestions, CH4 yield increased
      from 111 to 244 mL CH4 g VS added(-1), and the percentage of VS removed increased
      from 50% to 86%. For PL-VPW co-digestions, the corresponding values were
      increased from 158 to 223 mL CH4 g VS added(-1) and from 70% to 92% VS removed.
      Hemicelluloses and more than 50% of cellulose were degraded during anaerobic
      digestion. Thermal analyses indicated that the stabilization of the wastes during
      anaerobic digestion resulted in significantly less energy being released by
      digestate samples than fresh samples.

PMID- 23540358
TI  - Prenatal attitudes and parity predict selection into a U.S. child health program:
      a short report.
AB  - Public policies are a determinant of child health disparities; sound evaluation
      of these programs is essential for good governance. It is impossible in most
      countries to randomize assignment into child health programs that directly offer
      benefits. In the absence of this, researchers face the threat of selection bias
      the idea that there are innate, immeasurable differences between those who take
      up treatment and those who don't. In the field of Program Evaluation we are most
      concerned with the differences between the eligible people who take-up a program
      and the eligible people who choose not to enroll. Using a case study of a large
      U.S. nutrition program, this report illustrates how the perceived benefits of
      participation may affect the decision to take-up a program. In turn, this
      highlights sources of potential selection bias. Using data from a longitudinal
      study of mothers and infants conducted between May and December of 2005, I show
      that attitudes and beliefs prenatally toward breastfeeding determine enrollment
      in a U.S nutrition program that offers free Infant Formula. I also find that the
      significance of the selection bias differs by parity. Analysis reveals that
      maternal attitudinal responses are more highly predictive of future behavior,
      compared to standard demographic variables. In sum, this paper makes a case for
      rigorously understanding the factors that determine take-up of a program and how
      those factors can modify the results of a program evaluation. 

PMID- 23540360
TI  - 'Faking til you make it': social capital accumulation of individuals on low
      incomes living in contrasting socio-economic neighbourhoods and its implications
      for health and wellbeing.
AB  - People on low-income living in low socio-economic neighbourhoods have poorer
      health in comparison with those living in advantaged neighbourhoods. To explore
      neighbourhood effects on health and social capital creation, the experiences of
      low-income people living in contrasting socio-economic neighbourhoods were
      compared, in order to examine how low-income status and differing levels of
      neighbourhood resources contributed to perceived health and wellbeing.
      Quantitative and qualitative data were analysed: survey data from 601 individuals
      living in contrasting socio-economic areas and in-depth interviews with a new
      sample of 24 individuals on low-incomes. The study was guided by Bourdieu's
      theory of practice, which examines how social inequalities are created and
      reproduced through the relationship between individuals' varying resources of
      economic, social and cultural capital. This included an examination of individual
      life histories, cultural distinction and how social positions are reproduced.
      Participants' accounts of their early life experience showed how parental socio
      economic position and socially patterned events taking place across the life
      course, created different opportunities for social network creation, choice of
      neighbourhood and levels of resources available throughout life, all of which can
      influence health and wellbeing. A definition of poverty by whether an individual
      or household has sufficient income at a particular point in time was an
      inadequate measure of disadvantage. This static measure of 'low income' as a
      category disguised a number of different ways in which disadvantage was
      experienced or, conversely, how life course events could mitigate the impact of
      low-income. This study found that the resources necessary to create social
      capital such as cultural capital and the ability to socially network, differed
      according to the socio-economic status of the neighbourhood, and that living in
      an advantaged area does not automatically guarantee access to potentially
      beneficial social networks.

PMID- 23540359
TI  - Socioeconomic status, health behavior, and leukocyte telomere length in the
      National Health and Nutrition Examination Survey, 1999-2002.
AB  - The purpose of this study was to examine the association between socioeconomic
      status (SES) and leukocyte telomere length (LTL) - a marker of cell aging that
      has been linked to stressful life circumstances - in a nationally representative,
      socioeconomically and ethnically diverse sample of US adults aged 20-84. Using
      data from the National Health and Nutrition Examination Survey (NHANES), 1999
      2002, we found that respondents who completed less than a high school education
      had significantly shorter telomeres than those who graduated from college. Income
      was not associated with LTL. African-Americans had significantly longer telomeres
      than whites, but there were no significant racial/ethnic differences in the
      association between education and telomere length. Finally, we found that the
      association between education and LTL was partially mediated by smoking and body
      mass index but not by drinking or sedentary behavior.

PMID- 23540361
TI  - The relationship between five different measures of structural social capital,
      medical examination outcomes, and mortality.
AB  - Higher social capital is associated with improved mental and physical health and
      reduced risk of premature mortality. We explored the relationship between five
      measures of structural social capital and 1) intermediate health outcomes
      (elevated C-reactive protein, cholesterol, blood pressure, and serum fibrinogen)
      and 2) distal outcomes (cardiovascular and all cause mortality). We did so using
      the National Health and Nutrition Examination Survey III 1988-1994 linked to the
      National Death Index with mortality follow-up through 2006. We employed ordinary
      least squares regression for the intermediate outcomes, seemingly unrelated
      regression (SUR) to consider combined effects, and Cox proportionate hazards
      models for mortality outcomes. We then performed extensive sensitivity analyses,
      exploring the contribution of various variables and reverse causality. We find
      that our measures of social capital did not predict statistically significant
      changes in the laboratory biomarkers we study. Nevertheless, belonging to
      organizations or attending church >12 times per year were associated with reduced
      all cause mortality (hazard ratio [HR] = 0.81, 95% confidence interval [CI] =
      0.70-0.93 and HR = 0.72, 95% CI = 0.60-0.86, respectively). In SUR analyses,
      however, combined laboratory values were significant for all measures of social
      capital we study with the exception of visits to neighbors. This suggests that
      some forms of structural social capital improve survival through small changes in
      multiple measures of biological risk factors rather than moderate or large
      changes in any one measure.

PMID- 23540362
TI  - Cross-sectional study of ethnic differences in the utility of area deprivation
      measures to target socioeconomically deprived individuals.
AB  - Area deprivation measures provide a pragmatic tool for targeting public health
      interventions at socioeconomically deprived individuals. Ethnic minority groups
      in the UK experience higher levels of socioeconomic deprivation and certain
      associated diseases than the White population. The aim of this study was to
      explore ethnic differences in the utility of area deprivation measures as a tool
      for targeting socioeconomically deprived individuals. We carried out a cross
      sectional study using the Health Survey for England 2004. 7208 participants aged
      16-64 years from the four largest ethnic groups in England (White, Indian,
      Pakistani and Black Caribbean) were included. The main outcome measures were
      percentage agreement, sensitivity and positive predictive value (PPV) of area
      deprivation, measured using Index of Multiple Deprivation 2004, in relation to
      individual socioeconomic position (measured by education, occupation, income,
      housing tenure and car access). We found that levels of both area and individual
      deprivation were higher in the Pakistani and Black Caribbean groups compared to
      the White group. Across all measures, agreement was lower in the Pakistani (50.9
      63.4%) and Black Caribbean (61.0-70.1%) groups than the White (67.2-82.4%) group.
      However, sensitivity was higher in the Pakistani (0.56-0.64) and Black Caribbean
      (0.59-0.66) groups compared to the White group (0.24-0.38) and PPV was at least
      as high. The results for the Indian group were intermediate. We conclude that, in
      spite of lower agreement, area deprivation is better at identifying individual
      deprivation in ethnic minority groups. There was no evidence that area based
      targeting of public health interventions will disadvantage ethnic minority
      groups.

PMID- 23540363
TI  - Individual-level social capital and self-rated health in Japan: an application of
      the Resource Generator.
AB  - Despite accumulating evidence of associations between social capital and health
      in public health research, a criticism of the field has been that researchers
      have exclusively focused on concepts of social cohesion to the exclusion of
      individual-level approaches. In the present study, we evaluated the association
      between social capital measured by the Resource Generator (an individual-level
      assessment of access to social capital) and self-rated health among Japanese
      population in a cross-sectional study. A postal survey of 4000 randomly selected
      residents in Okayama City (western Japan) was conducted in February 2009. We
      divided the overall scores from the Resource Generator Japan scale into
      quartiles. Odds ratios (ORs) and 95% confidence intervals (CIs) for self-rated
      health were calculated separately by sex. Individuals with the highest quartile
      of scores had significantly lower odds of poor health compared to the lowest
      group after covariate adjustment among both men and women (men; OR: 0.45, 95% CI:
      0.24-0.86, women; OR: 0.44, 95% CI: 0.25-0.79, respectively) and there were also
      significant dose-response relationships. In the sub-domains of Resource Generator
      Japan scale, a differential pattern was observed by sex. Women showed a clear
      dose-response relationship with health across all four sub-scales (domestic
      resources, expert advice, personal skills, and problem solving resources). In
      contrast, only the domain of expert advice exhibited a strong association with
      men's health. Among both men and women individual-level social capital measured
      by the Resource Generator was related to reduced odds of poor health even after
      taking into account individual confounders. Although we cannot exclude reverse
      causation due to the cross-sectional design, our study adds to the accumulating
      evidence of the potential utility of the Resource Generator for evaluating the
      relationship between individual-level access to social capital and health.

PMID- 23540364
TI  - How effective has the essential health package been in improving priority setting
      in low income countries?
AB  - The Essential Health Care Package (EHP) approach has been promoted as a tool for
      guiding priority setting (PS) in Low Income Countries (LICs). This approach was
      expected to improve PS by; (i) providing credible evidence, (ii) improving
      efficiency, (iii) making PS more transparent, explicit and objective, (iv)
      increasing public empowerment and accountability; and (v) improving equity. To
      date, there is paucity of literature discussing the degree to which the EHP
      approach has met these expectations. This review paper fills this gap. We
      demonstrate that the EHP approach has only marginally met some of the above
      expectations. While this has been blamed on the lack of resources and capacity to
      deliver the package, we argue that limited attention paid to the PS process and
      the context, failure to institute and strengthen the capacity of PS institutions,
      and lack of an inbuilt process of monitoring and evaluating the implementation of
      the approach, may have also contributed to the EHP's not meeting its
      expectations. While we use the example of the EHP approach, this discussion is
      relevant to any PS approach and the proposed recommendations (if implemented),
      would contribute to strengthening PS in LICs.

PMID- 23540365
TI  - Effects of neighborhood violence and perceptions of neighborhood safety on
      depressive symptoms of older adults.
AB  - Violent crime within a neighborhood as well as perceptions of neighborhood safety
      may impact the depressive symptoms experienced by community-dwelling older
      people. Most studies examining the influences of neighborhood characteristics on
      mental health have included either objective indicators or subjective perceptions
      and most operationalize neighborhood as a function of socioeconomic status. This
      study examines the effects that objectively assessed neighborhood violent crime
      and subjective perceptions of neighborhood safety in tandem have on depressive
      symptoms. The sample identified using random-digit-dialing procedures included
      5688 persons aged 50-74 living in New Jersey (USA). Using multilevel structural
      equation analyses, we tested the hypothesis that higher levels of neighborhood
      violent crime and poorer perceptions of neighborhood safety are associated with
      higher levels of depressive symptoms, controlling for age, sex, and household
      income. Results supported the hypotheses. We conclude that interventions at the
      neighborhood level that reduce violent crime may be needed to compliment efforts
      at the individual level in order to reduce the depressive symptoms experienced by
      older people.

PMID- 23540367
TI  - The impacts of health insurance on health care utilization among the older people
      in China.
AB  - In an effort to solve the problems that exist in the current health care system,
      the Chinese government has announced three different types of health insurance
      programs. We examine the impacts of these programs (Urban Employee Basic Medical
      Insurance (UEBMI), Urban Resident Basic Medical Insurance (URBMI), and New
      Cooperative Medical Scheme (NCMS)) on health care utilization among older people
      in two provinces of China - Zhejiang and Gansu. The data comes from the pilot
      survey of the China Health and Retirement Longitudinal Study (CHARLS) collected
      in 2008, which contains 2685 individuals in 1570 households. We use a two-part
      model to analyze outpatient care. The first part is a binary equation modeling
      the probability of any use of outpatient service; For the second part, we use a
      zero-truncated Poisson model and a generalized linear model with a gamma
      distribution and a log link to explain the number of outpatient visits and the
      level of out-of-pocket (OOP) payments conditional on at least one visit to a
      service provider, respectively. For the inpatient care, the logistic regression
      is employed to predict the probability of being hospitalized. All analyses are
      weighted and marginal effects are reported. We find that compared with people
      without health insurance, people with UEBMI and URBMI are more likely to use
      outpatient services and people with UEBMI have less OOP payments in Zhejiang
      while in Gansu province, people with NCMS are less likely to have outpatient
      visits, while people with UEBMI are more likely to be hospitalized. In addition,
      among those who have at least one outpatient visit, different insurance types do
      not make much difference in terms of the number of outpatient visits in both
      provinces. Our study indicates that although the health insurance programs have
      some positive impacts on the health care utilization, these impacts are still
      limited.

PMID- 23540366
TI  - Neighborhood disorder and telomeres: connecting children's exposure to community
      level stress and cellular response.
AB  - Our objective was to explore the utility of salivary telomere length (sTL) as an
      early indicator of neighborhood-level social environmental risk during child
      development. We therefore tested the hypothesis that sTL would be associated with
      markers of social stress exposure in children. Children age 4-14 from 87
      neighborhoods were recruited through five urban schools in New Orleans,
      Louisiana, U.S. Data were collected at the level of the child, family/household,
      and neighborhood. DNA was obtained from saliva using commercially available kits
      and sTL was determined for 104 children using quantitative PCR. Analysis was
      performed on 99 children who had complete data including sTL, social
      environmental stress, and additional covariates. The mean sTL value was 7.4 T/S
      (telomere signal/single-copy signal) ratio units (+/-2.4, range = 2.5-18.0), and
      4.7% of the variance in sTL was attributed to differences across neighborhoods.
      Children living in neighborhoods characterized by high disorder had an sTL value
      3.2 units lower than children not living in high disordered environments (p <
      0.05) and their odds of having low relative sTL (defined as <1 standard deviation
      below standardized Z-score mean) values was 3.43 times that of children not
      living in high disorder environments (adjusted OR = 3.43, 95% CI = 1.22, 9.62).
      Our findings are consistent with previous studies in adults demonstrating a
      strong link between psychosocial stress and sTL obtained from peripheral blood,
      consistent with previous studies in youth demonstrating an association between
      early life stress and sTL obtained from buccal cell DNA and offer increased
      support for the hypothesis that sTL represents a non-invasive biological
      indicator of psychosocial stress exposure (i.e., neighborhood disorder) able to
      reflect differences in stress exposure levels even in young children.

PMID- 23540368
TI  - Changing expectations concerning life-extending treatment: the relevance of
      opportunity cost.
AB  - Rising public expectations and health care costs along with demographic ageing
      raise questions about whether individuals should consider the drain on community
      resources when deciding whether to have expensive, life-extending medical
      interventions towards the end of their lifespan. All respondents (n = 208) in
      this novel, policy-capturing study were prepared to nominate an age along their
      life trajectory where they would likely decline a life-extending medical
      intervention indicating a "sense of limits" or "reasonableness" associated with
      the concept of a natural lifespan. The results showed that individuals altered
      end-of-life decisions in circumstances of higher opportunity cost and competing
      need but their propensity to do so was affected by their age, gender, and their
      expectations of medical progress. Other within-person factors (type of scarcity,
      treatment side effects, and health at diagnosis) affected the age one would
      decline a medical intervention in the face of a life threatening illness. Between
      person predictors of this age included subjective life expectancy and attitude to
      health spending. The results suggest possibilities for building on this sense of
      reasonableness in public discussions of the opportunity cost of current health
      care resource allocation and by having physicians consider appropriate ways of
      presenting cost of treatment in end-of life contexts.

PMID- 23540369
TI  - How do national guidelines frame clinical ethics practice? A comparative analysis
      of guidelines from the US, the UK, Canada and France.
AB  - International policies regulating clinical ethics committees' (CEC) roles are non
      existent. Nonetheless, CECs have established themselves in several countries and
      there exist striking differences in the way these work. This international
      practice variation stems from the ways CECs developed, within particular legal,
      political, social and professional contexts. National guidelines and normative
      documents have been published in many countries regarding CECs. To better
      understand CECs' evolution and differences in various countries, we reviewed
      guidelines, position statements and normative papers which describe and frame the
      development of CECs in the United States, the United Kingdom, Canada and France.
      Systematic content analysis addressed guideline development, CECs' roles,
      consultation methods and CEC members' education requirements. Differing contexts
      informed the ways in which guidelines were developed. American CECs, established
      within a strongly litigious context are perceived to play strong decision-making
      roles, whereas British CECs, encouraged by clinicians, endorse a more supportive
      model. Canadian guidelines focus on the role of the ethicist, while the French
      model is interested in a theoretical interdisciplinary approach. This analysis
      shows important challenges facing the implementation of accountable CECs in
      different contexts and can help inform future policy development.

PMID- 23540370
TI  - Scientific decision-making and stakeholder consultations: the case of salt
      recommendations.
AB  - Scientific advisory committees (SACs) are seen as "boundary organisations"
      working at the interface between science, policy and society. Although their
      narrowly defined remit of risk assessment is anchored in notions of rationality,
      objectivity, and reason, in reality, their sources for developing recommendations
      are not limited to scientific evidence. There is a growing expectation to involve
      non-scientific sources of information in the formation of knowledge, including
      the expectation of stakeholder consultation in forming recommendations. Such a
      move towards "democratisation" of scientific processes of decision-making within
      SACs has been described and often studied as "post-normal science" (PNS)
      (Funtowicz & Ravetz, 1993). In the current paper we examine the application of
      PNS in practice through a study of stakeholder consultations within the workings
      of the UK Scientific Advisory Committee for Nutrition (SACN). We use the
      theoretical insights from PNS-related studies to structure the analysis and
      examine the way in which PNS tenets resonate with the practices of SACN. We have
      selected a particular case of the SACN UK recommendations for salt as it is
      characterized by scientific controversy, uncertainty, vested interests and value
      conflict. We apply the tenets of PNS through documentary analysis of the SACN
      Salt Subgroup (SSG) consultation documents published in 2002/2003: the minutes of
      the 5 SACN SSG's meetings which included summary of the SACN SSG's stakeholder
      consultation and the SSG's responses to the consultation. The analysis suggests
      that the SACN consultation can be construed as a process of managing sources of
      risk to its organisation. Thus, rather than being an evidence of post-normal
      scientific practice, engagement became a mechanism for confirming the specific
      framing of science that is resonant with technocratic models of science holding
      authority over the facts. The implications for PNS theory are discussed.

PMID- 23540371
TI  - Utilizing community health worker data for program management and evaluation:
      systems for data quality assessments and baseline results from Rwanda.
AB  - Community health workers (CHWs) have and continue to play a pivotal role in
      health services delivery in many resource-constrained environments. The data
      routinely generated through these programs are increasingly relied upon for
      providing information for program management, evaluation and quality assurance.
      However, there are few published results on the quality of CHW-generated data,
      and what information exists suggests quality is low. An ongoing challenge is the
      lack of routine systems for CHW data quality assessments (DQAs). In this paper,
      we describe a system developed for CHW DQAs and results of the first formal
      assessment in southern Kayonza, Rwanda, May-June 2011. We discuss considerations
      for other programs interested in adopting such systems. While the results
      identified gaps in the current data quality, the assessment also identified
      opportunities for strengthening the data to ensure suitable levels of quality for
      use in management and evaluation.

PMID- 23540372
TI  - Do different types of financial support after illness or injury affect socio
      economic outcomes? A natural experiment in New Zealand.
AB  - BACKGROUND: In New Zealand, people unable to work due to an illness may be
      eligible for a means-tested benefit whereas injured people are eligible for a
      wide range of support including earnings-related compensation through the no
      fault Accident Compensation Corporation (ACC). The effect of this difference on
      socio-economic outcomes has not been investigated before. METHODS: A comparative
      cohort study was undertaken of stroke versus injury. Individuals aged 18-64, who
      had a first-stroke (n = 109) were matched by age, sex and functional impairment
      with injured individuals (n = 429) participating in the Prospective Outcomes of
      Injury Study. Data were collected by interview 3.5 and 12 months after stroke or
      injury. Logistic regression adjusting for the matching variables at 3.5 months,
      and functional impairment at 12 months, was undertaken. RESULTS: Median personal
      income declined by 60% over 12 months for the Stroke Group compared to 13%
      decline in the Injury Group. Decline in income was greater for those in both
      groups who had a higher income initially, and for those who had not returned to
      work. The proportion of the Stroke Group reporting 'Fairly low/low' standard of
      living increased from 8% to 28% and 'Just/not enough' income increased from 35%
      to 61% whereas the Injury Group increased only from 5% to 12% and 33%-44%
      respectively. The odds of reporting low standard of living and income inadequacy
      at 12 months were significantly less for the Injury Group. Despite earnings
      related compensation (80% of income), the odds of being back at work were greater
      for the Injury Group compared to the Stroke Group (Adjusted Odds Ratio 3.1; 95%
      CI 1.7-5.6). CONCLUSIONS: These findings support the conclusions that earnings
      related compensation and rehabilitative support, available to injured people via
      ACC, largely prevents the downward spiral into poverty and ill health. It also
      appears to enhance return to work though residual confounding cannot be ruled
      out.

PMID- 23540374
TI  - Iodine(III)-mediated umpolung of bromide salts for the ethoxybromination of
      enamides.
AB  - Using (diacetoxyiodo)benzene in conjunction with simple bromide salts in ethanol
      allows the regioselective ethoxybromination of a wide range of enamides, thus
      yielding highly versatile alpha-bromo hemiaminals, which can then be engaged in a
      broad array of transformations.

PMID- 23540373
TI  - Misrecognition of need: women's experiences of and explanations for undergoing
      cesarean delivery.
AB  - International rates of operative delivery are consistently higher than the World
      Health Organization determined is appropriate. This suggests that factors other
      than clinical indications contribute to cesarean section. Data presented here are
      from interviews with 115 mothers on the postnatal ward of a hospital in Northeast
      England during February 2006 to March 2009 after the women underwent either
      unscheduled or scheduled cesarean childbirth. Using thematic content analysis, we
      found women's accounts of their experiences largely portrayed cesarean section as
      everything that they had wanted to avoid, but necessary given their situations.
      Contrary to popular suggestion, the data did not indicate impersonalized medical
      practice, or that cesareans were being performed 'on request.' The categorization
      of cesareans into 'emergency' and 'elective' did not reflect maternal
      experiences. Rather, many unscheduled cesareans were conducted without
      indications of fetal distress and most scheduled cesareans were not booked
      because of 'choice.' The authoritative knowledge that influenced maternal
      perceptions of the need to undergo operative delivery included moving forward
      from 'prolonged' labor and scheduling cesarean as a prophylactic to avoid
      anticipated psychological or physical harm. In spontaneously defending themselves
      against stigma from the 'too posh to push' label that is currently common in the
      media, women portrayed debate on the appropriateness of cesarean childbirth as a
      social critique instead of a health issue. The findings suggest the 'need' for
      some cesareans is due to misrecognition of indications by all involved. The
      factors underlying many cesareans may actually be modifiable, but informed choice
      and healthful outcomes are impeded by lack of awareness regarding the benefits of
      labor on the fetal transition to extrauterine life, the maternal desire for
      predictability in their parturition and recovery experiences, and possibly lack
      of sufficient experience for providers in a variety of vaginal delivery scenarios
      (non-progressive labor, breech presentation, and/or after previous cesarean).

PMID- 23540375
TI  - A 6 month, prospective, observational study of PDE5 inhibitor treatment
      persistence and adherence in Latin American men with erectile dysfunction.
AB  - OBJECTIVES: To assess persistence/adherence rates of phosphodiesterase type-5
      inhibitor (PDE5I) on-demand dosing in Latin American men with erectile
      dysfunction (ED), and explore patient characteristics and treatment factors that
      may be predictive for PDE5I persistence and adherence. METHODS: Men from Brazil,
      Mexico, and Venezuela with ED who were naive to PDE5Is were prescribed
      sildenafil, tadalafil, vardenafil, or lodenafil on-demand dosing and asked to
      provide information about PDE5I use at baseline and at 1, 3, and 6 months.
      Patients were persistent if they used >=1 dose during the 4 week period prior to
      each evaluation. Patients were adherent if they complied with dosing instructions
      during most recent dose. Main outcome measures included Persistence and Adherence
      Questionnaire (PAQ), Partner Relationship Questionnaire (PRQ), Self-Esteem and
      Relationship (SEAR) Questionnaire, and International Index of Erectile Function
      (IIEF). Multivariate logistic regression was used to identify factors associated
      with persistence and adherence. RESULTS: A total of 511 men were enrolled; most
      had mild to moderate ED (77.1%); 317 patients (62.0%) were prescribed tadalafil,
      116 (22.7%) sildenafil, 75 (14.7%) vardenafil, and 3 (0.6%) lodenafil (not
      further analyzed). A total of 340 patients (66.5%) were 'persistent' at 6 months;
      345 (67.5%) were 'adherent'. Persistence and adherence were associated with age,
      education level, and ED duration. Reasons for non-persistence included medication
      cost and lack of efficacy. Study limitations included its design, brief
      observation period, its bias observed toward tadalafil selection; its dependence
      on patient self-reporting, limited number of factors that were analyzed for
      persistence/adherence association, its small number of participating patients and
      Latin American countries, and inherent differences in PDE5I preference and
      medical practices. CONCLUSION: Approximately two-thirds of PDE5I-naive, Latin
      American men with ED were persistent and adherent after 6 months of therapy.
      Factors like education level, ED severity, and ED duration were associated with
      persistence and adherence; additional study is warranted to investigate the
      predictive value of these factors.

PMID- 23540376
TI  - Dynamic mechanical compression of devitalized articular cartilage does not
      activate latent TGF-beta.
AB  - A growing body of research has highlighted the role that mechanical forces play
      in the activation of latent TGF-beta in biological tissues. In synovial joints,
      it has recently been demonstrated that the mechanical shearing of synovial fluid,
      induced during joint motion, rapidly activates a large fraction of its soluble
      latent TGF-beta content. Based on this observation, the primary hypothesis of the
      current study is that the mechanical deformation of articular cartilage, induced
      by dynamic joint motion, can similarly activate the large stores of latent TGF
      beta bound to the tissue extracellular matrix (ECM). Here, devitalized deep zone
      articular cartilage cylindrical explants (n=84) were subjected to continuous
      dynamic mechanical loading (low strain: +/-2% or high strain: +/-7.5% at 0.5Hz)
      for up to 15h or maintained unloaded. TGF-beta activation was measured in these
      samples over time while accounting for the active TGF-beta that remains bound to
      the cartilage ECM. Results indicate that TGF-beta1 is present in cartilage at
      high levels (68.5+/-20.6ng/mL) and resides predominantly in the latent form (>98%
      of total). Under dynamic loading, active TGF-beta1 levels did not statistically
      increase from the initial value nor the corresponding unloaded control values for
      any test, indicating that physiologic dynamic compression of cartilage is unable
      to directly activate ECM-bound latent TGF-beta via purely mechanical pathways and
      leading us to reject the hypothesis of this study. These results suggest that
      deep zone articular chondrocytes must alternatively obtain access to active TGF
      beta through chemical-mediated activation and further suggest that mechanical
      deformation is unlikely to directly activate the ECM-bound latent TGF-beta of
      various other tissues, such as muscle, ligament, and tendon.

PMID- 23540377
TI  - Cervical spine intervertebral kinematics with respect to the head are different
      during flexion and extension motions.
AB  - Previous dynamic imaging studies of the cervical spine have focused entirely on
      intervertebral kinematics while neglecting to investigate the relationship
      between head motion and intervertebral motion. Specifically, it is unknown if the
      relationship between head and intervertebral kinematics is affected by movement
      direction. We tested the hypothesis that there would be no difference in sagittal
      plane intervertebral angles at identical head orientations during the flexion and
      extension movements. Nineteen asymptomatic subjects performed continuous head
      flexion-extension movements while biplane radiographs were collected at 30 images
      per second. A previously validated model-based volumetric tracking process
      determined three-dimensional vertebral position with sub-millimeter accuracy
      throughout the flexion-extension motion. Head movement was recorded at 60 Hz
      using conventional motion analysis and reflective markers. Intervertebral angles
      were determined at identical head orientations during the flexion and extension
      movements. Cervical motion segments were in a more extended orientation during
      flexion and in a more flexed orientation during extension for any given head
      orientation. The results suggest that static radiographs cannot accurately
      represent vertebral orientation during dynamic motion. Further, data should be
      collected during both flexion and extension movements when investigating
      intervertebral kinematics with respect to global head orientation. Also, in vitro
      protocols that use intervertebral total range of motion as validation criteria
      may be improved by assessing model fidelity using continuous intervertebral
      kinematics in flexion and in extension. Finally, musculoskeletal models of the
      head and cervical spine should account for the direction of head motion when
      determining muscle moment arms because vertebral orientations (and therefore
      muscle attachment sites) are dependent on the direction of head motion.

PMID- 23540378
TI  - [Glycaemic control and complications of diabetes: what about?].
AB  - In France, 2.8 millions of patients have type 2 diabetes, which is a well
      established risk factor for cardiovascular disease. In about 15 years, several
      large clinical trials tried to study the relationship between a tight glycaemic
      control and the occurrence of micro- and macroangiopathy. Meta-analyses of
      targeting intensive versus conventional glycaemic control focused on divergent
      results. In type 1 diabetes, a tight glycaemic control reduced the occurrence of
      microangiopathy whereas more time, at least 5 years is needed to reduce
      macroangiopathy. Conclusions drawn from studies are less clear for type 2
      diabetes and depend on the caracteristics of the population studied, particularly
      for retinopathy. When microalbuminuria is the judgement criteria, its progression
      is lower in the intensive group than in the conventional one and it takes more
      than about 5 years to emerge; the impact on glomerular filtration rate is less
      clear. Worries about the excess of mortality observed in the ACCORD study in the
      intensive treatment group were not described in other studies. The decrease of
      mortality was not associated with an intensive glyceamic control. Intensified
      multifactorial intervention is finally needed to improve microangiopathy.

PMID- 23540380
TI  - [Consensus guideline on the contents of clinical trial protocols].

PMID- 23540379
TI  - Hepatitis C genotype 4 with normal transaminases: correlation with fibrosis and
      response to treatment, a cohort Egyptian study of 4277 patients.
AB  - BACKGROUND AND OBJECTIVE: Chronic hepatitis C virus (HCV) patients with
      persistently normal transaminases represent a subgroup of patients with mild,
      slowly progressive disease, natural history, and optimal management of these
      patients needs to be investigated in Egypt. Our aim is to assess the severity of
      hepatic fibrosis and response to therapy in a cohort of Egyptian HCV patients
      with normal transaminases. PATIENTS AND METHODS: Retrospective demographics,
      laboratory, histological features and treatment outcome of patients included in
      the national program for the control of viral hepatitis in Egypt since 2007 were
      collected. Combined pegylated IFN/ribavirin therapy was given for patients with
      fibrosis stage >= F1 and elevated transaminases while those with normal
      transaminase; therapy was initiated only in patients with fibrosis stage >= F2.
      RESULTS: Normal ALT and AST were detected in 1308/4277 (30.6%) and 1662/4277
      (38.9%) patients, respectively, while both enzymes were normal in 943 patients
      (22%). Multivariate regression analysis showed that lower AFP and higher
      platelets count (compared with elevated transaminases group) were significantly
      correlated with normal transaminases (P<0.01), however, HCV-RNA levels did not
      show such significance. The number of patients with HAI score >= A1 was
      significantly lower in normal than elevated transaminases (36.5% vs 40.9%,
      respectively, P<0.01) and patients with fibrosis >= F2 was significantly lower in
      normal than elevated transaminases (36.4%) and (43%), respectively (P<0.01).
      There was no significant correlation between baseline transaminases levels and
      response to treatment. CONCLUSION: Normal transaminases are frequently
      encountered in chronic HCV Egyptian patients (22%). They show low AFP level, mild
      degree of activity and stage of fibrosis with no correlation with response to
      therapy.

PMID- 23540381
TI  - [Hepatotoxicity in patients treated with endothelin receptor antagonists:
      systematic review and meta-analysis of randomized clinical trials].
AB  - BACKGROUND AND OBJECTIVE: We evaluated the risk of hepatotoxicity associated to
      endothelin receptor antagonists. PATIENTS AND METHOD: Systematic searches in
      PubMed/MEDLINE, the Cochrane Library as well as regulatory agencies websites were
      performed. Randomized controlled trials in patients receiving endothelin receptor
      antagonists (bosentan, sitaxentan or ambrisentan) in at least one treatment group
      were included. Prior to data extraction, definitions of hepatotoxicity were
      established. Effect sizes with 95% confidence intervals were calculated using
      random effects models. Heterogeneity was analysed using Cochran's Q and I(2)
      tests. Publication bias was assessed using Egger's method and funnel plots were
      generated. RESULTS: Twenty-one trials met the inclusion criteria (3,644
      patients). Bosentan was the evaluated drug in 1,689 (74%) patients who received
      endothelin receptor antagonists. Compared with controls, relative risk for any
      hepatic adverse reaction was 2.92 (1.85-4.62; I(2)=30.6%). When hepatotoxicity
      was defined as elevations of liver alanine or aspartate aminotransferases equal
      or greater than 3 times the upper limit of normal, relative risk was 2.98 (1.69
      5.25; I(2) = 40.9%). No evidence of publication bias was found (Egger's method: p
      = 0.68). CONCLUSIONS: Our results suggest an increased risk of hepatotoxicity in
      patients receiving endothelin receptor antagonists. Given the limited data
      available for endothelin receptor antagonists other than bosentan, it is not
      possible to draw firm conclusions about the individual risk associated for the
      remaining endothelin receptor antagonists.

PMID- 23540382
TI  - [Symmetric benign lipomatosis; Madelung syndrome].

PMID- 23540383
TI  - [Reasons for an injury compensation programme for adverse vaccine-related events
      in Spain].

PMID- 23540384
TI  - [Vulgar pemphigus].

PMID- 23540385
TI  - [Medium-term results of a Day Hospital insulin therapy program for patients with
      type 2 diabetes mellitus].
AB  - BACKGROUND AND OBJECTIVE: The profile of the patient with type 2 diabetes
      mellitus (DM2) who requires insulin therapy is very diverse as are the results of
      this intervention and short/middle-term patient management. We evaluated the
      midterm results of an outpatient program starting insulin therapy with>=2 insulin
      injections/day in terms of metabolic control in different groups of patients.
      PATIENTS AND METHOD: We analyzed prospectively 131 patients with DM2, without
      previous insulin treatment, who were prescribed treatment with>=2 insulin
      injections/day and who were enrolled in a specific ambulatory program in order to
      start insulin therapy in a Day Hospital for 6 months. RESULTS: The initial
      glycosylated hemoglobin (HbA1c) was 11.3 (2.3) % and decreased to 6.3 (1.4) % in
      6 months, with HbA1c<7% in 72.5% of them. The group of recently diagnosed
      patients (<3 months, symptomatic severe hyperglycemia, D-group) were younger
      (57.1 [10.8] vs 64.2 [12.1] years; P<.01) and had a higher starting HbA1c (12.1
      [1.8] vs 10.5 [2.5] %; P<.001) than patients included in the program for oral
      antidiabetic drugs' failure (F-group). At the end of the program 50% of D-group
      patients did not need insulin (6.3% on F-group [P<.001]). There were no
      significant differences in either of 2 groups at study ends according to the
      final treatment scheme. CONCLUSIONS: Counselling patients with DM2 to start
      insulin with more than one injection per day in Day Hospital setting achieves and
      maintains a good metabolic control in the medium term in different patient
      profiles. Among symptomatic and recently diagnosed patients, insulin therapy can
      be stopped in 50% of them at the medium term.

PMID- 23540386
TI  - [Deep brain stimulation. Twenty-five years later].

PMID- 23540387
TI  - [Pustular lesions and fever].

PMID- 23540388
TI  - [New tuberculosis drugs in resistant and multiresistant tuberculosis].
AB  - Drug-resistant tuberculosis is a globally emerging problem with a rising
      incidence. According to the WHO in 2008, 17% of strains of Mycobacterium
      tuberculosis, in untreated cases were resistant to at least one drug and 3.6%
      were resistant to rifampicin and isoniazid, which is called multidrug-resistant
      tuberculosis. The problem is greater in patients previously treated and in some
      countries, where rates of multidrug resistance reach 60%. Approximately 5% of
      multidrug-resistant tuberculosis patients are also resistant to any
      fluoroquinolone and at least one injectable drug, being called extensively drug
      resistant tuberculosis. The treatment of these forms of tuberculosis requires the
      use of second-line drugs, which causes higher cost, higher toxicity and a longer
      duration of treatment. There is a need for new compounds with efficacy and safety
      profiles better than those currently used to treat these forms of tuberculosis.
      In the last decade different drugs have being reassessed and appeared, which are
      at different stages of development. 

PMID- 23540389
TI  - [Clinical teaching in the 21st century--the curriculum for evidence-based
      practice].

PMID- 23540390
TI  - [Degenerative osteoarthritis, osteoporosis and fractures: controversies and
      evidences].
AB  - Osteoarthritis and osteoporosis are both common conditions in the elderly but
      their association has long remained obscure. Recently published studies show that
      patients with osteoarthritis have higher bone mass but no corresponding decrease
      in fracture risk. This has been proposed to be due to an increased rate of falls
      in these patients. Multi-disciplinary interventions, vitamin D supplementation
      and bisphosphonates can play a role on preventing fractures among osteoarthritis
      patients, but evidence on their efficacy is scarce and of poor quality. 

PMID- 23540391
TI  - [Non-Hodgkin lymphomas after remission of human immunodeficiency virus-associated
      lymphomas in the highly active antiretroviral therapy era].

PMID- 23540393
TI  - Scalable patterning of one-dimensional dangling bond rows on hydrogenated
      Si(001).
AB  - Silicon dangling bonds exposed on the monohydride silicon (001) (Si(001):H)
      surface are highly reactive, thus enabling site-selective absorption of atoms and
      single molecules into custom patterns designed through the controlled removal of
      hydrogen atoms. Current implementations of high-resolution hydrogen lithography
      on the Si(001):H surface rely on sequential removal of hydrogen atoms using the
      tip of a scanning probe microscope. Here, we present a scalable thermal process
      that yields very long rows of single dimer wide silicon dangling bonds suitable
      for self-assembly of atoms and molecules into one-dimensional structures of
      unprecedented length on Si(001):H. The row consists of the standard buckled Si
      dimer and an unexpected flat dimer configuration.

PMID- 23540392
TI  - Impact of aromatase genetic variation on hormone levels and global outcome after
      severe TBI.
AB  - Although experimental traumatic brain injury (TBI) studies support estradiol as a
      neuroprotectant and potent stimulator of neuroplasticity, clinical studies
      suggest a negative association between endogenous estradiol profiles and
      mortality/poor outcomes. However, no studies have evaluated associations with
      cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450
      [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with
      severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone
      ratios (E2:T) were measured using CSF and serum samples and compared to healthy
      controls. Eighteen tagging and four functional single-nucleotide polymorphisms
      (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and
      Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF
      estradiol over time versus controls. CSF testosterone was initially high, but
      declined over time. E2/T ratios were initially low, compared to controls, but
      rose over time. Higher mean E2/T ratio in bivariate analysis was associated with
      lower mortality (p=0.019) and better GOS-6 scores (p=0.030). rs2470152 influenced
      CSF E2/T ratio and also serum and CSF testosterone (p<=0.05 all comparisons).
      Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse
      GOS-6 scores (p<=0.05, all comparisons), and those with>1 risk SNP variant had a
      higher risk for poor outcome, compared with those with <=1 risk variant. TBI
      results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In
      contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated
      with better outcome. Further, genetic variation in CYP19A1 influences both
      hormone dynamics and outcome post-TBI.

PMID- 23540394
TI  - Tobramycin is a suppressor of premature termination codons.
AB  - Premature translation terminations (PTCs) constitute the molecular basis of many
      genetic diseases, including cystic fibrosis, as they lead to the synthesis of
      truncated non-functional or partially functional protein. Suppression of
      translation terminations at PTCs (read-through) has been developed as a
      therapeutic strategy to restore full-length protein in several genetic diseases.
      Phenotypic consequences of PTCs can be exacerbated by the nonsense-mediated mRNA
      decay (NMD) pathway that detects and degrades mRNA containing PTC. Modulation of
      NMD, therefore, is also of interest as a potential target for the suppression
      therapy. Tobramycin is an aminoglycoside antibiotic, normally used to treat
      Pseudomonas aeruginosa pulmonary infection in CF patients. In the present study,
      by using yeast as a genetic system, we have examined the ability of Tobramycin to
      suppress PTCs as a function of the presence or absence of NMD. Results
      demonstrate that Tobramycin exhibits read-through ability on PTCs and
      preferentially in absence of NMD. 

PMID- 23540395
TI  - iTRAQ-based proteomic profiling of the barnacle Balanus amphitrite in response to
      the antifouling compound meleagrin.
AB  - Marine biofouling refers to the unwanted accumulation of fouling organisms, such
      as barnacles, on artificial surfaces, resulting in severe consequences for marine
      industries. Meleagrin is a potential nontoxic antifoulant that is isolated from
      the fungus Penicillium sp.; however, its mechanistic effect mode of action on
      larval settlement remains unknown. Here, we applied iTRAQ coupled with 2D LC
      MS/MS proteomic analysis to investigate the effect of meleagrin on the proteomic
      expression profile of cyprid development and aging in the barnacle Balanus
      amphitrite . Fifty proteins were differentially expressed in response to
      treatment with meleagrin, among which 26 proteins were associated with cyprid
      development/aging and 24 were specifically associated with the meleagrin
      treatment. The 66 proteins that were associated with aging only remained
      unaltered during exposure to meleagrin. Using KEGG analysis, those proteins were
      assigned to several groups, including metabolic pathways, ECM-receptor
      interactions, and the regulation of the actin cytoskeleton. Among the 24 proteins
      that were not related to the development/aging process, expression of the cyprid
      major protein (CMP), a vitellogenin-like protein, increased after the meleagrin
      treatment, which suggested that meleagrin might affect the endocrine system and
      prevent the larval molting cycle. With the exception of the chitin binding
      protein that mediates the molting process and ATPase-mediated energy processes,
      the majority of proteins with significant effects in previous studies in response
      to cyprid treatment with butenolide and polyether B remained unchanged in the
      present study, suggesting that meleagrin may exhibit a different mechanism.

PMID- 23540397
TI  - [Vaccination of teenagers. Mission: impossible?].

PMID- 23540398
TI  - Isthmus-dependent right atrial flutter as the leading cause of atrial
      tachycardias after surgical atrial septal defect repair.
AB  - OBJECTIVES: The purpose of this study was to evaluate clinical and
      electrophysiologic characteristics of AT in patients after surgical ASD repair as
      well as outcome after ablation. BACKGROUND: Atrial tachycardias (AT) are a common
      complication after surgical closure of an atrial septal defect (ASD). METHODS:
      From a prospective ablation database we analyzed data of patients with a history
      of ASD repair who presented to our institution for AT ablation. We investigated
      ECG characteristics and the electrophysiologic mechanism of AT in this collective
      and analyzed follow-up data. RESULTS: Data of 54 patients (47.3 +/- 14.5 years,
      35 females) were included. In 30 patients (55.6%) ASD had been closed by direct
      suture, 24 patients (44.4%) had a patch for ASD repair without significant
      difference in terms of gender and age at the time of the procedure (p=0.234,
      p=0.231). In 42 patients (77.8%), electrophysiological studies were performed in
      AT. All patients had right atrial macro-reentrant AT. The leading mechanism was
      isthmus-dependent right atrial flutter in 29 patients (69.0%) with clockwise
      atrial activation in 41%. The mechanism of AT (typical atrial flutter (n=29),
      atriotomy-dependent flutter (n=7), and double loop flutter (n=5)) did not differ
      with regard to type of surgery. Only 70.6% of patients with proven isthmus
      dependent counter-clockwise atrial flutter presented with an ECG morphology
      typical for this mechanism. However, all clockwise typical atrial flutter
      patients showed the characteristic positive P-waves in the inferior leads. Of
      note, 83.3% of clockwise typical flutter ECGs had long isoelectric lines (mean
      74.5 ms). Follow-up was complete in 45 of 54 patients. During a mean follow-up of
      7.7 +/- 3.7 years, 27 patients (60%) remained free of any arrhythmia, two
      patients had AT recurrence with different mechanisms compared to the first
      procedure and underwent successful ablation. Five patients (11%) developed atrial
      fibrillation. CONCLUSION: Isthmus dependent right atrial flutter is the leading
      AT mechanism in patients with a history of ASD repair. The mechanism of atrial
      flutter did not differ in relation to the mode of ASD closure (direct suture
      versus patch closure). ECG characteristics of the tachycardia may be misleading
      as they are more often atypical in patients after ASD repair.

PMID- 23540399
TI  - Clinical outcomes after ventricular assist device implantation in adults with
      complex congenital heart disease.
AB  - BACKGROUND: There are minimal data regarding ventricular assist device (VAD)
      implantation in adult patients with complex congenital heart disease (CHD).
      METHODS: The medical records of 6 adult patients with complex CHD who underwent
      VAD implantation were retrospectively analyzed to characterize pre-operative
      clinical status, implantation techniques and challenges, post-operative
      management, and post-operative outcomes. RESULTS: All patients had a systemic
      right ventricle, including 2 with single-ventricle physiology. The average age at
      VAD implantation was 41 years. The implanted VADs included 1 HeartMate XVE, 3
      HeartMate II (Thoratec Corp, Pleasanton, CA), 1 Jarvik 2000 (Jarvik Heart, New
      York, NY), and 1 HeartWare HVAD (HeartWare Inc, Framingham, MA). In-hospital
      outcomes included no sub-pulmonic ventricular failure, no VAD thrombosis or
      mechanical failure, 30-day mortality in 1 patient, non-fatal sub-arachnoid
      hemorrhage in 1 patient, and sustained ventricular tachycardia requiring
      unsynchronized direct current cardioversion in 1 patient. Of the 5 patients who
      survived to discharge, 1 patient received 171 days of VAD support before cardiac
      transplantation and survived for 1,484 days after transplantation; 1 patient
      received 262 days of VAD support before out-of-hospital death of unknown
      etiology; 1 patient had received VAD support for 988 days as of December 1, 2012,
      while awaiting a transplant; and 2 patients who received VADs as destination
      therapy had received 577 and 493 days of VAD support, respectively, and were
      still alive as of December 1, 2012. CONCLUSIONS: This case series characterizes
      important post-operative management challenges and clinical outcomes associated
      with VAD implantation as a bridge-to-transplant or as destination therapy in
      adult patients with complex CHD.

PMID- 23540400
TI  - Anti-reflux surgery for lung transplant recipients in the presence of impedance
      detected duodenogastroesophageal reflux and bronchiolitis obliterans syndrome: a
      study of efficacy and safety.
AB  - BACKGROUND: The aim of this study was to determine the safety of anti-reflux
      surgery for lung transplant recipients and assess its effect on lung function.
      METHODS: We retrospectively collected and analyzed data from all lung transplant
      recipients who underwent anti-reflux surgery at St Mary's Hospital London from
      July 2005 to May 2012. The indications for surgery were histologic evidence of
      gastroesophageal reflux aspiration on bronchoscopy biopsy specimens or a positive
      impedance study with symptomatic reflux or a consistent decline/fluctuating
      forced expiratory volume in 1 second (FEV(1)). We studied the difference in mean
      FEV(1) and rate of change of FEV(1), before and after fundoplication. The safety
      of anti-reflux surgery was determined by post-operative morbidity and mortality
      and compared with predicted figures, using a risk prediction model based on the P
      POSSUM (Portsmouth Modification of the Physiological and Operative Severity Score
      for Enumeration of Mortality and Morbidity) assessment. RESULTS: Forty patients
      underwent laparoscopic Nissen fundoplication. Overall, mean FEV(1) declined from
      2119 +/- 890 to 1967 +/- 1027 ml (p = 0.027), and mean rate of change in FEV(1)
      improved from -2.42 +/- 4.40 to -0.41 +/- 1.77 ml/day (p = 0.007). Patients
      referred for fundoplication based on histologic evidence of reflux (n = 9) showed
      an improvement in rate of change of FEV(1) from -3.39 +/- 6.00 to -0.17 +/- 1.50
      ml/day (p = 0.057), and those with positive impedance study and consistent
      decline in FEV(1) (n = 13) showed a significant improvement from -3.62 +/- 3.35
      to -0.74 +/- 2.33 ml (p = 0.021). Actual and predicted morbidity was 2.5% and
      31%, respectively. Actual and predicted 30-day mortality was 0% and 1.9%,
      respectively. CONCLUSIONS: Anti-reflux surgery is safe for lung transplant
      recipients and results in an improvement in the rate of change in FEV(1) despite
      a decline in mean FEV(1) post-operatively.

PMID- 23540401
TI  - Defining pulsatility during continuous-flow ventricular assist device support.
AB  - Continuous-flow ventricular assist devices (CVADs) have gained widespread use as
      an effective clinical therapy for patients with advanced-stage heart failure.
      Axial and centrifugal CVADs have been successfully used as bridge-to-transplant
      and destination therapy. CVADs are smaller, more reliable, and less complex than
      the first-generation pulsatile-flow ventricular assist devices. Despite their
      recent clinical success, arteriovenous malformations, gastrointestinal bleeding,
      hemorrhagic strokes, aortic valve insufficiency, and valve fusion have been
      reported in heart failure patients supported by CVADs. It has been hypothesized
      that diminished arterial pressure and flow pulsatility delivered by CVAD may be a
      contributing factor to these adverse events. Subsequently, the clinical
      significance of vascular pulsatility continues to be highly debated. Studies
      comparing pulsatile-flow and continuous-flow support have presented conflicting
      findings, largely due to variations in device operation, support duration, and
      the criteria used to quantify pulsatility. Traditional measurements of pulse
      pressure and pulsatility index are less effective at quantifying pulsatility for
      mechanically derived flows, particularly with the growing trend of CVAD speed
      modulation to achieve various pulsatile flow patterns. Kinetic measurements of
      energy equivalent pressure and surplus hemodynamic energy can better quantify
      pulsatile energies, yet technologic and conceptual challenges are impeding their
      clinical adaption. A review of methods for quantifying vascular pulsatility and
      their application as a research tool for investigating physiologic responses to
      CVAD support are presented.

PMID- 23540402
TI  - Remote post-conditioning reduces hypoxic damage early after experimental stroke.
AB  - OBJECTIVES: Given that reliable markers for early ischemic brain damage are
      lacking, we set out to test whether pimonidazole can be used as a reliable tool
      in the quantification of hypoxic insults, at early time points following
      experimental stroke. METHODS: We have used semi-quantitative Western blotting
      detection of pimonidazole adducts in a rat model of reversible middle cerebral
      artery occlusion (MCAO), treated with remote post-conditioning. RESULTS: First,
      we demonstrated that a linear relationship exist between pimonidazole binding in
      the ischemic hemisphere and duration of ischemia, in animals subjected to 5, 15,
      30, or 60 minutes of occlusion followed by 120 minutes of reflow. Then we showed
      a significant reduction in pimonidazole binding in the infarcted hemisphere, when
      rats with 60 minutes of MCAO, immediately after establishment of cerebral reflow,
      had 3*15 minutes intermittent hind limb ischemia followed by 24-hour survival. We
      analysed the middle cerebral arteries from animals with 60 minutes of MCAO and
      early remote post-conditioning, followed by 30 minutes, 24, or 48 hours of
      reflow. At 24 hours of reflow increases in phosphorylated protein kinase C-alpha
      with concomitantly increased levels of p38 phosphorylation were observed.
      CONCLUSIONS: Our investigation demonstrates that pimonidazole can be used for
      quantifying ischemic impact in stroke, even after very short survival times. It
      furthermore shows that early remote post-conditioning reduces ischemic damage,
      probably through hyperpolarization and reduced reflow vasospasm in the conduit
      middle cerebral arteries.

PMID- 23540403
TI  - Continuous cerebrovascular reactivity monitoring and autoregulation monitoring
      identify similar lower limits of autoregulation in patients undergoing
      cardiopulmonary bypass.
AB  - OBJECTIVES: Cerebrovascular autoregulation can be monitored with a moving linear
      correlation of blood pressure to cerebral blood flow velocity (mean velocity
      index, Mx) during cardiopulmonary bypass (CPB). Vascular reactivity can be
      monitored with a moving linear correlation of blood pressure to cerebral blood
      volume trended with near-infrared spectroscopy (hemoglobin volume index, HVx). We
      hypothesized that the lower limits of autoregulation (LLA) and the optimal blood
      pressure (ABPopt) associated with the most active autoregulation could be
      determined by HVx in patients undergoing CPB. METHODS: Adult patients (n = 109)
      who underwent CPB for cardiac surgery had monitoring of both autoregulation (Mx)
      and vascular reactivity (HVx). Individual curves of Mx and HVx were constructed
      by placing each in 5 mmHg bins. The LLA and ABPopt for each subject were then
      identified by both methods and compared for agreement by correlation analysis and
      Bland-Altman. RESULTS: The average LLA defined by Mx compared to HVx were
      comparable (66+/-13 and 66+/-12 mmHg). Correlation between the LLA defined by Mx
      and HVx was significant (Pearson r = 0.2867; P = 0.0068). The average ABPopt with
      the most robust autoregulation by Mx was comparable to HVx (75+/-11 and 74+/-13
      mmHg) with significant correlation (Pearson r = 0.5915; P < or =0.0001).
      DISCUSSION: Autoregulation and vascular reactivity monitoring are expected to be
      distinct, as flow and volume have different phasic relationships to pressure when
      cerebrovascular autoregulation is active. However, the two metrics have good
      agreement when identifying the LLA and optimal blood pressure in patients during
      CPB.

PMID- 23540404
TI  - The protective effect of berberine against neuronal damage by inhibiting matrix
      metalloproteinase-9 and laminin degradation in experimental autoimmune
      encephalomyelitis.
AB  - OBJECTIVE: This study aims to assess the protective effect of berberine against
      neuronal damage in the brain parenchyma of mice with experimental autoimmune
      encephalomyelitis (EAE). METHODS: EAE was induced in female C57 BL/6 mice with
      myelin oligodendrocyte glycoprotein 35-55 amino acid peptide. The berberine
      treatment was initiated on the day of disease onset and administered daily until
      the mice were sacrificed. Terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling (TUNEL) assay, gelatin gel, and gelatin in situ
      zymography were analysed in this study. RESULTS: Berberine reduced the TUNEL
      positive neuronal cells of EAE mice. Gelatin gel and gelatin in situ zymography
      showed up-regulation of gelatinase activity, which was mainly located in neurons
      and colocalized with remarkable laminin degradation in EAE mice. Berberine
      significantly inhibited gelatinase activity and reduced the laminin degradation
      in EAE mice. DISCUSSION: Our data suggest that berberine could provide protection
      against neuronal damage in EAE by inhibiting gelatinase activity and reducing
      laminin degradation. These findings provide further support that berberine can be
      a potential therapeutic agent for multiple sclerosis.

PMID- 23540405
TI  - Differential nuclear factor-kappa B phosphorylation induced by lipopolysaccharide
      in the hippocampus of P2X7 receptor knockout mouse.
AB  - OBJECTIVE: Lipopolysaccharide (LPS) stimulates the innate immune response in the
      brain through nuclear factor-kappaB (NF-kappaB) signaling. Since purinergic
      signals activate NF-kappaB through the P2X7 receptor (P2X7R), we investigated the
      roles of P2X7R in neuronal NF-kappaB phosphorylation in the mouse hippocampus
      under basal conditions and P2X7R deletion following LPS treatment in vivo.
      METHODS: We performed immunohistochemical studies for neuronal NF-kappaB
      phosphorylation in the hippocampi of wild type (WT) and P2X7R knockout (KO) mice
      under basal conditions and LPS treatment. RESULTS: LPS treatment did not induce
      neuronal damages in both WT and P2X7(-/-) KO mice. In WT animals, LPS treatment
      increased p65-Ser276 and p65-Ser311 NF-kappaB phosphorylations in hippocampal
      neurons. However, p52-Ser865, p52-Ser869, p65-Ser468, p65-Ser529, and p65-Ser536
      NF-kappaB phosphorylations were unaffected by LPS treatment. In P2X7(-/-) KO
      mice, neuronal p65-Ser311 NF-kappaB phosphorylation in vehicle-treated animals
      was higher than that in WT animals. In addition, both p65-Ser276 and p65-Ser311
      NF-kappaB phosphorylations were unaffected by LPS treatment in P2X7(-/-) KO mice.
      DISCUSSION: These findings indicate that P2X7R may be involved in LPS-induced
      inflammatory response in neurons, and that p65-Ser311 NF-kappaB phosphorylation
      may compensate for the loss function of P2X7R by as yet unknown factors.

PMID- 23540406
TI  - Comparison between the formula 1/2ABC and 2/3Sh in intracerebral parenchyma
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: The 1/2ABC formula is the method most commonly used in
      clinical practice to rapidly estimate intracerebral hemorrhage (ICH) volume. We
      aimed to compare this method with the alternative '2/3Sh' formula for both
      regularly and irregularly-shaped hematomas. METHODS: Computed tomography (CT)
      images from 344 ICH patients (median volume: 16.66 ml) were retrospectively
      reviewed. According to the maximum slice, the shape was classified into regular
      or irregular (multilobular, conical, and other). Volumes as determined by the
      1/2ABC and 2/3Sh formulas were compared against the gold standard, computer
      assisted planimetry, for various hematoma shapes. RESULTS: With the 1/2ABC
      method, errors were seen non-significantly more frequently for irregularly-shaped
      hematomas [OR: 2.85 (95% CI: 0.65-12.50)]. The 1/2ABC method misclassified a
      greater proportion of hematomas as greater or less than 30 ml in volume: 7.0%
      (95% CI: 6.0-9.9%). Both the 1/2ABC and 2/3Sh formulas correlated well with gold
      standard (correlation coefficients >0.9 for each shape). While there was no
      statistically significant measurement error bias for either method, the 95%
      confidence intervals of the limit of agreement for 2/3Sh were tighter: -0.22 ml (
      4.7-4.25 ml) versus 2.50 ml (-10.35-15.34 ml). Measurement errors were
      significantly greater with the 1/2ABC method, for both regular and irregular
      hematomas [1.17 ml (0.48-2.83 ml) versus 0.88 ml (0.42-1.68 ml) and 2.65 ml (1.07
      5.88 ml) versus 0.99 ml (0.47-2.28 ml); P<0.05, respectively], although the
      magnitude of error would only rarely be clinically relevant for regular
      hematomas. Errors were most evident in assessing multilobular-shaped hematomas
      [6.49 ml (3.35-13.98 ml) versus 1.86 ml (0.96-9.94 ml); P<0.001]. CONCLUSIONS:
      The 2/3Sh formula leads to fewer clinically-relevant hematoma volume
      misclassifications than the 1/2ABC formula, and is particularly superior in
      estimating volumes of irregularly-shaped hematomas.

PMID- 23540407
TI  - The role of vein in microvascular decompression for hemifacial spasm: a clinical
      analysis of 15 cases.
AB  - OBJECTIVES: The objective of this study is to investigate the clinical
      characteristics, intraoperative findings, complications, and outcomes in these
      patients with hemifacial spasm (HFS) caused by venous compression. METHODS: We
      analyzed 15 patients who underwent microvascular decompression (MVD) for HFS
      caused by venous compression performed at the University of Pittsburgh Medical
      Center between 1 January 2000 and 31 December 2007. Thirteen of 15 patients
      underwent repeat MVD, and two patients underwent their first MVD. Clinical data
      were collected to verify vein as real offending vessel for all of 15 patients
      with HFS. The mean follow-up period was 4.13 years (range: 1.29-6.76 years).
      RESULTS: Thirteen patients with repeat MVDs had vein as the offending vessel,
      such as series of small venule, small veins, and dilated venous stump. The
      remaining two patients who underwent the first MVD had vein as the only offending
      vessel. In the first MVD for 13 patients, lateral spread response (LSR)
      disappeared in five patients (38.5%). In the repeat MVD for these 13 patients,
      LSR disappeared after the vein was decompressed completely in nine patients
      (69.2%). An excellent surgical outcome was observed in all the 11 patients with
      four patients lost during the follow-up period. Post-operative complications were
      observed in 12 patients included hearing loss, cerebrospinal fluid leakage,
      worsening facial palsy, difficulty swallowing, dilpopia, and ataxia. CONCLUSIONS:
      Vein can play an important role and can be the offending vessel in MVD for HFS.
      Women with platysmal involvement and tonus seem to have higher chance of vein as
      an offending vessel. These patients that have residual LSR at the end of the
      procedure should undergo exploration for a vein to prevent persistent HFS.
      Intraoperative monitoring with LSR is an effective tool to evaluate adequate
      decompression to vein. Although the long-term outcome is excellent for venous
      compression, the complication rate is much higher. To decrease the complication
      rate, gentle retraction of the cerebellum and 'low-power' coagulation of the vein
      might be helpful.

PMID- 23540408
TI  - Chronological changes and effects of AMP-activated kinase in the hippocampal CA1
      region after transient forebrain ischemia in gerbils.
AB  - OBJECTIVES: Adenosine monophosphate-activated kinase (AMPK) is an energy-specific
      sensor within the central nervous system. In this study, we observed AMPK and its
      phosphorylated form (pAMPK) in the hippocampal CA1 region after 5 minutes of
      transient forebrain ischemia. In addition, we also investigated the effects of
      Compound C, an AMPK inhibitor, against ischemic damage in gerbils. METHODS:
      Adenosine monophosphate-activated kinase and pAMPK immunoreactivity was observed
      in the hippocampal CA1 region at various time points after ischemia and Compound
      C was intraperitoneally administered to gerbils immediately after reperfusion and
      the animals were sacrificed at 5 days after ischemia/reperfusion. RESULTS:
      Adenosine monophosphate-activated kinase immunoreactivity was transiently
      increased in the hippocampal CA1 region 1-2 days after ischemia/reperfusion,
      while AMPK immunoreactivity was almost undetectable in the stratum pyramidale of
      the CA1 region 4-7 days after ischemia/reperfusion. The administration of
      Compound C caused a dose-dependent decrease in the ischemia-induced hyperactive
      behavior, the depletion of ATP, and lactate accumulation in the hippocampal CA1
      region within 24 hours after ischemia/reperfusion. In addition, the
      administration of Compound C decreased reactive gliosis (astrocytes and
      microglia) and increased the number of cresyl violet-positive neurons when
      compared to the vehicle-treated group at 5 days post-ischemia/reperfusion.
      CONCLUSION: These results suggest that AMPK is transiently phosphorylated
      following forebrain ischemia in the hippocampal CA1 region and inhibition of AMPK
      has neuroprotective effects against ischemic damage through the reduction of ATP
      depletion and lactate accumulation in the hippocampal CA1 region.

PMID- 23540409
TI  - NDRG2 is involved in anti-apoptosis induced by electroacupuncture pretreatment
      after focal cerebral ischemia in rats.
AB  - OBJECTIVE: We first reported that electroacupuncture (EA) pretreatment at the
      Baihui acupoint (GV20) induces ischemic tolerance. Our recent study demonstrated
      that N-Myc downstream-regulated gene 2 (NDRG2) expression was up-regulated
      following transient focal cerebral ischemia. Therefore, we investigated whether
      NDRG2 was involved in the ischemic tolerance induced by EA pretreatment in rats.
      METHODS: Twenty-four hours after the end of the last EA pretreatment, focal
      cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 120
      minutes in male Sprague-Dawley rats. The neurobehavioral score, infarction
      volume, and extent of neuronal apoptosis were evaluated at 24 hours after
      reperfusion. The expression of NDRG2 in the brain was evaluated by reverse
      transcriptase-polymerase chain reaction (RT-PCR), western blotting, and
      immunofluorescent staining. RESULTS: Electroacupuncture pretreatment decreased
      infarction volume and improved neurologic scores at 24 hours after reperfusion.
      Double immunofluorescence revealed that NDRG2 expression in astrocytes was
      suppressed in the EA group at 24 hours after reperfusion, and that NDRG2 protein
      expression was weak in the nucleus and strong in the cytoplasm of the EA group,
      but strong in the nucleus of the MCAO group. Triple immunofluorescent staining
      for terminal deoxynucleotidyl transferase nick-end labeling (TUNEL), NDRG2, and
      4',6-diamidino-2-phenylindole (DAPI) showed that NDRG2 co-localised with
      apoptotic cells. Moreover, the number of apoptotic cells decreased with the
      attenuation of NDRG2 expression in the EA group compared to the MCAO group.
      CONCLUSION: Our results indicated that NDRG2 is involved in anti-apoptosis
      induced by EA pretreatment after focal cerebral ischemia in rats. N-Myc
      downstream-regulated gene 2 was involved in EA pretreatment-induced cerebral
      ischemic tolerance. These findings may be important for our understanding of the
      cellular signaling pathways induced by EA pretreatment.

PMID- 23540410
TI  - Protective effect of low molecular weight polyethylene glycol on the repair of
      experimentally damaged neural membranes in rat's spinal cord.
AB  - OBJECTIVES: Membrane disruption is one of the main factors that cause axonal
      damage and functional deficits manifested in spinal cord injury (SCI). In this
      study, we used polyethylene glycol (PEG) to induce immediate membrane sealing and
      to promote functional recovery after SCI. METHODS: The effects of PEG (200-2000
      Da) on the damaged membrane were monitored by means of spinal cord evoked
      potentials (SCEPs) in an SCI model in rats. In a parallel study, membranes of
      neural cells were mechanically damaged in culture by ultrasound waves (20 kHz)
      and the repairing effects of PEGs were examined afterwards at the single cell
      level. RESULTS: Analysis of SCEPs showed that the smaller the PEG, the higher was
      the ultimate recovery of SCEP (i.e., 200 Da caused 49.5% and 2000 Da up to
      16.3%). The rate of recovery was maximum with a polynomial trend, when the
      damaged spinal cord was treated with PEG200 for 25 minutes. The analysis of
      survival rate of mechanically damaged cells in culture, measured by MTT assay,
      showed that again smaller PEGs, caused higher membrane sealing rate; 77.8+/-3.5
      for PEG400 (20% w/w) vs 32.1+/-6.9 for PEG2000 (20% w/w). The large ones (PEG1000
      and 2000) that presented minor repair at low concentration, showed no significant
      sealing effects at high concentrations (>50%). CONCLUSION: Our studies showed
      that the application of low molecular weight PEGs, (<50% w/w) can be considered
      as one of the effective early treatments for SCI.

PMID- 23540411
TI  - Nitric oxide suppresses L-type calcium currents in basilar artery smooth muscle
      cells in rabbits.
AB  - OBJECTIVES: Nitric oxide (NO) is well known to be a vasodilator, and NO donor
      compounds are currently used for treating vasospasm following subarachnoid
      hemorrhage. However, the action mechanism of cerebral vascular relaxation is not
      yet clear. L-type calcium channels have been determined to play an essential role
      in smooth muscle contraction. To investigate the role of L-type calcium channels
      in NO-induced relaxation of basilar smooth muscle cells, we examined the effect
      of the NO donor, sodium nitroprusside (SNP) on calcium (Ca2+) currents using
      smooth muscle cells isolated from a rabbit basilar artery. METHOD: The smooth
      muscle cells were isolated from rabbit basilar artery by enzyme treatment. To
      identify L-type Ca2+ currents, we used cesium chloride, a potassium channel
      blocker and Bay K8644, an activator of L-type Ca2+ channel. RESULTS: The L-type
      calcium currents (91+/-13.0 pA; n = 11) were significantly reduced by SNP (32+/-5
      pA; n = 11; P<0.05). 1H-[1,2,4] Oxadiazolo [4,3-a] quinoxalin-1-one, a 3',5'
      cyclic guanosine monophosphate inhibitor, blocked the effect of SNP on L-type
      Ca2+ currents, and similar results were obtained after the application of 7
      nitroindazole, a specific NO synthase inhibitor. Furthermore, inward currents
      were enhanced by Bay K8644 (170+/-22 pA; n = 5) and were suppressed by SNP (54+/
      13 pA; n = 5; P<0.05). DISCUSSION: These results demonstrate that NO suppresses
      the L-type Ca2+ currents in rabbit basilar smooth muscle cells, and suggest that
      L-type Ca2+ channels may play a pivotal role in NO-induced vascular relaxation.

PMID- 23540412
TI  - ACE and ADD1 gene in extra and intracranial atherosclerosis in ischaemic stroke.
AB  - OBJECTIVE: Hypertension is closely linked to ischaemic stroke (IS) and
      atherosclerosis, but there are no studies correlating the candidate hypertensive
      gene, namely angiotensin converting enzyme (ACE) and adducin 1 (ADD1) with
      magnetic resonance angiographic (MRA) abnormality, therefore this study was
      undertaken. METHODS: Patients with magnetic resonance imaging (MRI) proven IS
      were included and their demography, stroke risk factors, and clinical findings
      were noted. Both intracranial (IC) and extracranial (EC) MRA were performed and
      more than 50% stenosis was considered significant. Angiotensin converting enzyme
      and ADD1 gene polymorphism was evaluated by polymerase chain reaction (PCR) both
      in patients and 188 controls. RESULTS: Angiotensin converting enzyme and ADD1
      polymorphism were performed in 151 patients whose median age was 60 years and
      26.5% were females. Magnetic resonance angiography was abnormal in 77.5%;
      extracranial magnetic resonance angiography (ECMRA) in 58.3%, and intracranial
      magnetic resonance angiography (ICMRA) in 66.7%. The conventional risk factors
      were not different between the IS patients with and without MRA abnormalities.
      The presence of DD genotype (OR 3.86, 95% CI 0.78-2.28, P = 0.0001) and ADD1 GW
      genotype (OR 2.05, 95% CI 1.28-3.27, P = 0.003) significantly increased the risk
      of IS compared to controls. Both genotype and allele frequency of ACE and ADD1
      were higher in MRA abnormal IS patients compared to controls; however, these were
      not significantly different between the patients with and without MRA
      abnormality. CONCLUSION: In IS patients, DD genotype and D allele of ACE gene and
      W allele of ADD1 gene were significantly related to MRA abnormality compared to
      controls but there was no association of ACE and ADD1 gene polymorphism in IS
      patients with MRA and without abnormality.

PMID- 23540413
TI  - Caspase-2 and caspase-8 trigger caspase-3 activation following 6-OHDA-induced
      stress in human dopaminergic neurons differentiated from ReNVM stem cells.
AB  - OBJECTIVES: The purpose of the study was to establish a suitable model to study
      Parkinson's disease (PD) pathogenesis in differentiated dopaminergic neurons
      (dDCN). The specific aim was to demonstrate the involvement of the caspase family
      and to identify specific caspases which are activated by 6-hydroxydopamine (6OHD)
      treatment leading to death of dDCN. METHODS: ReNcell VM cells were differentiated
      into dDCN and were exposed to 6OHD to induce stress. Western blot (WB) and double
      immunofluorescent analyses of caspases-2, -3, and -8 were carried out in
      untreated and 6OHD-treated dDCN. zVADfmk was used to determine if it could
      inhibit activation of caspases-2, -3, and -8 in dDCN following 6OHD-mediated
      stress. RESULTS: Our immunofluorescent and WB data showed that 6OHD triggered
      caspases-2 and -8 activation which in turn activated caspase-3 leading to death
      of dDCN. Additionally, WB analysis revealed that caspases-2, -3, and -8
      activation was reduced by zVADfmk in 6OHD-treated cells. DISCUSSION: The study
      showed that 6OHD-induced toxicity triggered caspase mediated death of dDCN. This
      finding is in support of previous studies using different PD model showing that
      6OHD can induce caspases-2 and -3 activation through apoptotic pathway and that
      both caspases can activate caspase-3 in PD. In addition, our results suggest that
      caspase-2 cause's cell death might be via an indirect NF kappaB route. This study
      has established a PD model which can provide better insight to PD pathogenesis on
      a biochemical and molecular level, leading to a better understanding of PD and
      potential for new treatments.

PMID- 23540414
TI  - Treatment of postaxial polydactyly type B.

PMID- 23540415
TI  - Mallet thumb.

PMID- 23540416
TI  - Exercise-induced strengthening of inter-digital connections in musicians.
AB  - OBJECTIVE: To investigate whether finger exercise affects surround inhibition in
      professional musicians as it was previously observed in non-musicians, we
      performed a transcranial magnetic stimulation (TMS) study in 13 healthy right
      handed professional musicians. METHODS: TMS was set to be triggered by self
      initiated flexion of the index finger at 3 ms after electromyography onset (self
      triggered TMS). Motor evoked potentials (MEPs) of the abductor digiti minimi
      (ADM) were measured before and at 0, 10, 20 and 30 min after 'single' (little
      finger abduction) and 'dual' (both index finger flexion and little finger
      abduction) exercise at 0.5 Hz for 30 min. RESULTS: Control and self-triggered
      MEPs were not different between the two exercise sessions. MEP enhancements were
      significantly greater in self-triggered TMS than control TMS after single
      exercise as well as dual exercise. CONCLUSION: This result demonstrates that MEP
      enhancement in self-triggered TMS was comparable between two exercise sessions in
      professional musicians, a result different from that observed in healthy non
      musicians. Enhanced self-triggered MEPs after isolated finger exercise suggest
      that inter-digital cortical connections are strengthened in musicians, presumably
      due to previous musical training. SIGNIFICANCE: Inter-digital cortical
      connections are strengthened in musicians and are not differently modulated by
      different types of short-term finger exercise.

PMID- 23540417
TI  - Parasympathetic activation is involved in reducing epileptiform discharges when
      listening to Mozart music.
AB  - OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial
      task scores, leading to what is known as the Mozart effect. Our previous work
      revealed the positive effects of Mozart K.448 in reducing epileptiform discharges
      in children with epilepsy. However, the mechanism remains unclear.
      parasympathetic activation has been shown to help seizure control in many
      studies. In this study, we investigated the effect of Mozart music on
      epileptiform discharges and autonomic activity. METHODS: Sixty-four epileptic
      children with epileptiform discharges were included. They all received
      electroencephalogram and electrocardiogram examinations simultaneously before,
      during, and after listening to Mozart K.448 or K.545. The total number of
      epileptiform discharges during each session (before, during, and after music)
      were divided by the duration (in minutes) of the session and then compared. Heart
      rate variability including time and frequency domain analysis was used to
      represent the autonomic function. RESULTS: The results showed that epileptiform
      discharges were significantly reduced during and right after listening to Mozart
      music (33.3 +/- 31.1% reduction, p<0.001, during Mozart K.448 and 38.6 +/- 43.3%
      reduction, p<0.001, during Mozart K.545) (28.1 +/- 43.2% reduction, p<0.001,
      after Mozart K.448 and 46.0 +/- 40.5% reduction, p<0.001, after Mozart K.545). No
      significant difference was noticed between the two pieces of music. The reduction
      was greatest in patients with generalized seizures and discharges. Significant
      increases in high-frequency (HF), the square root of the mean squared differences
      of successive RR intervals (RMSSD), the standard deviation of differences between
      adjacent RR intervals (SDSD), and a decrease in mean beats per minute (bpm) were
      found during listening to Mozart music. Most of the patients with reduced
      epileptiform discharges also showed a decreased LF/HF ratio, low-frequency
      normalized units (LF nu), mean bpm, and an increased high-frequency normalized
      units (HF nu). CONCLUSIONS: Listening to Mozart music decreased epileptiform
      discharges in children with epilepsy. The majority of these patients showed an
      increase in parasympathetic tone during music exposure. SIGNIFICANCE: Our results
      suggested that Mozart music stimuli induced parasympathetic activation which may
      be involved in the effect of music in reducing epileptiform discharges and the
      recurrence rate of seizures.

PMID- 23540418
TI  - Watching object related movements modulates mirror-like activity in parietal
      brain regions.
AB  - OBJECTIVE: We studied the activation of cortical motor and parietal areas during
      the observation of object related grasping movements. By manipulating the type of
      an object (realistic versus abstract) and the type of grasping (correct versus
      incorrect), we addressed the question how observing such object related movements
      influences cortical rhythmicity, especially the mu-rhythm, in the context of an
      "extended" human mirror neuron system (MNS). METHODS: Multichannel
      electroencephalogram (EEG) was recorded during the observation of different
      object-related grasping actions in twenty healthy subjects. Different movies were
      presented, showing sequences of correct or incorrect hand grasping actions
      related to an abstract or realistic (daily life) object. RESULTS: Event-related
      de/synchronization (ERD/ERS) analyses revealed a larger ERD in the upper alpha
      (10-12 Hz), beta (16-20 Hz) and gamma (36-40 Hz) frequency bands over parietal
      brain regions depending on the type of grasping. The type of object only
      influenced ERD patterns in the gamma band range (36-40 Hz) at parietal sites
      suggesting a strong relation of gamma band activity and cortical object
      representation. Abstract and realistic objects produced lower beta band
      synchronization at central sites only, whereas depending on the type of grasping
      an ERS in the upper alpha band (10-12 Hz) was observed. CONCLUSION: Depending on
      the type of the grasped object and the type of grasping stronger parietal
      cortical activation occurred during movement observation. SIGNIFICANCE:
      Discussing the results in terms of an "extended" human mirror neuron system
      (MNS), it could be concluded that beside sensorimotor areas a stronger
      involvement of parietal brain regions was found depending on the type of object
      and grasping movement observed.

PMID- 23540419
TI  - Modulation of oVEMP amplitudes by lateral head tilts.

PMID- 23540420
TI  - Predicting phenotypic variation from genotypes, phenotypes and a combination of
      the two.
AB  - A central challenge for medicine is to predict disease risk and treatment
      outcomes for individuals. But what kind of information should be used to make
      useful predictions in biology? One important cause of phenotypic variation is of
      course genetics. However genetic predictions have both practical and fundamental
      limitations: most genetic influences on a trait are usually unknown, and
      phenotypic variation is not just due to genetics. A pragmatic alternative is to
      use intermediate phenotypes such as gene expression and other molecular
      measurements to make predictions about later trait variation such as disease
      risk. Intermediate phenotypes are useful because they capture both genetic and
      non-genetic influences on a system, and can reflect both the current state of a
      system and its history. Here we discuss examples of both genetic and non-genetic
      approaches to predicting phenotypic variation. Moreover, we argue that it will be
      by combining these two sources of information-genetics and intermediate molecular
      phenotypes-that it will be possible to make accurate predictions about variation
      in many phenotypic traits, even if we will not always mechanistically understand
      why this is the case. In particular, we encourage the human genetics community to
      focus more on combining genetics with intermediate phenotypes when attempting to
      predict clinically relevant traits such as disease risk. 

PMID- 23540421
TI  - Accelerated protein engineering for chemical biotechnology via homologous
      recombination.
AB  - Protein engineering has traditionally relied on random mutagenesis strategies to
      generate diverse libraries, which require high-throughput screening or selection
      methods to identify rare variants. Alternatively, approaches to semi-rational
      library construction can be used to minimize the screening load and enhance the
      efficiency by which improved mutants may be identified. Such methods are
      typically limited to characterization of relatively few variants due to the
      difficulties in generating large rational libraries. New tools from synthetic
      biology, namely multiplexed DNA synthesis and homologous recombination, provide a
      promising avenue to rapidly construct large, rational libraries. These
      technologies also enable incorporation of synthetically encoded features that
      permit efficient characterization of the fitness of each mutant. Extension of
      these tools to protein library design could complement rational protein design
      cycles in an effort to more systematically search complex fitness landscapes. The
      highly parallelized nature with which such libraries can be generated also has
      the potential to expand directed protein evolution from single protein targets to
      protein networks whose concerted activities are required for the biological
      function of interest. 

PMID- 23540422
TI  - Design-based re-engineering of biosynthetic gene clusters: plug-and-play in
      practice.
AB  - Synthetic biology is revolutionizing the way in which the biosphere is explored
      for natural products. Through computational genome mining, thousands of
      biosynthetic gene clusters are being identified in microbial genomes, which
      constitute a rich source of potential novel pharmaceuticals. New methods are
      currently being devised to prioritize these gene clusters in terms of their
      potential for yielding biochemical novelty. High-potential gene clusters from any
      biological source can then be activated by 'refactoring' their native regulatory
      machinery, replacing it by synthetic, orthogonal regulation and optimizing enzyme
      expression to function effectively in an industry-compatible target host. Various
      part libraries and assembly technologies have recently been developed which
      facilitate this process. 

PMID- 23540423
TI  - [Being a physician... "from the peaks of Gredos to the Royal Academy of
      Medicine"].

PMID- 23540424
TI  - Fate of CuO and ZnO nano- and microparticles in the plant environment.
AB  - The environmental fate of metal oxide particles as a function of size was
      assessed by comparing the behavior of CuO or ZnO nanoparticles (NPs) to that of
      the corresponding microparticles (MPs) in a sand matrix, with and without wheat
      (Triticum aestivum L.) growth. After 14 days of incubation in the planted sand,
      the CuO and ZnO NPs were increased from their nominal sizes of <50 nm and <100
      nm, to ~317 nm and ~483 nm, respectively. Accordingly, the negative surface
      charge of colloids present in aqueous extracts from the sand amended with CuO (
      27.0 mV) and ZnO (-10.0 mV) NPs was reduced by the presence of plants, to -19.8
      mV and -6.0 mV, respectively. The surface charge of the MPs was not influenced by
      plants. Plant growth increased dissolution of NPs and MPs of both metal oxides in
      the sand from <0.3 mg/kg to about 1.0 mg/kg for the CuO products, and from <=0.6
      mg/kg to between 1.0 and 2.2 mg/kg for the Zn products. The NP or MP products
      reduced wheat root length by ~60% or ~50% from control levels; CuO was more toxic
      than ZnO. X-ray absorption spectroscopy (XAS) analysis showed that treatments
      with MPs or NPs of ZnO led to similar accumulations of Zn-phosphate species in
      the shoots, likely from dissolution of ZnO. Exposure to CuO NPs or MPs resulted
      in similar XAS spectra for Cu in the shoots explained by plant accumulation of
      both CuO and Cu(I)-sulfur complexes. These findings demonstrate the similarities
      between commercial NPs and MPs of CuO or ZnO in wheat plants, with greater root
      toxicity correlating with smaller particle size. Factors from the sand and the
      plant modified the aggregation or dissolution of both types of particles, thus,
      influencing their environmental fates.

PMID- 23540425
TI  - Is it safe to perform dental and cardiac valve surgeries concomitantly?
AB  - PURPOSE: Conventionally, dental surgery and cardiac valve replacement surgery
      (VRS) have been performed separately. Disadvantages of this approach include
      increased anesthetic and infection risks and increased costs. The authors
      hypothesized dental surgeries performed immediately before VRS would have similar
      mortality and morbidity outcomes and significantly decreased costs compared with
      those performed independently of VRS. MATERIALS AND METHODS: An institutional
      review board-approved retrospective study was completed comparing outcomes for 17
      patients undergoing concomitant cardiac VRS and invasive dental procedures with
      outcomes for 16 patients undergoing similar procedures by a conventional
      approach. RESULTS: The conventional group had a significant increase in ejection
      fraction (11% vs 6.7%; P < .05) and no difference in the incidence of prosthetic
      valve endocarditis or other cardiac complications. The concomitant group had
      longer overall operating room time (389 vs 328 min) but significantly shorter
      anesthesia time (428 vs 553 min) than the conventional group. Length of stay in
      the intensive care unit was similar (6.7 days) and overall hospital stays were
      shorter in the concomitant group (14.5 vs 18.2 days). Cost analysis showed the
      concomitant group's overall costs were significantly lower than those for the
      conventional group. CONCLUSION: There was no significant difference in cardiac
      outcomes between the concomitant and conventional groups. In addition, each
      patient in the concomitant approach saved an average of $6,669. Thus, concomitant
      dental surgery and cardiac VRS may be considered a safe and cost-effective
      approach that may lead to decreases in overall health care costs.

PMID- 23540426
TI  - Intra-arch elastics technique: a novel method for controlling the abutment/soft
      tissue interface during implant reconstruction of the orofacial region.
AB  - In the past 30 years, composite microvascular free tissue transfer has become a
      popular and highly successful option for the reconstruction of defects in the
      head and neck region. However, inherent shortcomings exist with free tissue
      transfer in that the imported tissue often fails to adequately replicate the
      characteristics of the native tissues. This can lead to difficulties when
      attempting reconstruction from a surgical and prosthetic standpoint. Endosseous
      implants are often required to adequately retain prostheses, and management of
      the peri-implant soft tissues represents a critical challenge for the oral and
      maxillofacial surgeon. This report describes a novel technique for controlling
      the implant-abutment-soft tissue interface and the advantages of this technique
      as it pertains to orofacial reconstruction. 

PMID- 23540427
TI  - Intraosseous leiomyosarcoma of the mandible: a case report.
AB  - Leiomyosarcomas are rare smooth muscle tumors that can occur anywhere in the
      body. These tumors rarely occur in the head and neck owing to the limited amount
      of smooth muscle in the region. The clinical diagnosis of leiomyosarcoma is
      challenging because of the nonspecific presentation of the disease. The most
      definitive diagnosis is based on tissue biopsy or surgical resection and
      histopathologic confirmation. A case of intraosseous leiomyosarcoma of the
      mandible and a review of the literature are presented. 

PMID- 23540428
TI  - Quality of life after maxillectomy and prosthetic obturator rehabilitation.
AB  - PURPOSE: Surgical resection of midface neoplasms and subsequent reconstruction
      have been shown to have significant negative effects on quality of life (QOL).
      The purpose of this pilot study was to assess individuals' health-related QOL
      after maxillectomy and reconstruction with a prosthetic obturator. MATERIALS AND
      METHODS: The QOL of 25 of 43 patients who underwent maxillectomy and prosthetic
      obturator reconstruction at the University of California-San Francisco was
      assessed using 3 questionnaires: University of Washington Quality of Life version
      4 (UWQOL), Obturator Functioning Scale (OFS), and Mental Health Inventory (MHI).
      RESULTS: The response rate to the QOL questionnaires was 92% (23 of 25 patients).
      Time elapsed from maxillectomy and prosthetic obturator reconstruction to the QOL
      survey response ranged from 0.3 to 6.6 years (mean, 2.7 years; standard deviation
      [SD], 1.9 years). The post-treatment mean QOL scores were 77.3 (SD, 13.6) for
      UWQOL, 72.0 (SD, 12.6) for OFS, and 4.5 (SD, 0.9) for Mental Health Inventory.
      Individuals who received adjuvant radiation scored lower for speech and
      appearance (OFS, P = .05, P = .03, respectively) as well as for saliva and
      overall QOL (UWQOL, P = .02, P = .08, respectively). There was a strong
      correlation between QOL scores in OFS and UWQOL questionnaires (r = 0.78, P <
      .001). CONCLUSION: The results of this pilot study suggest that postoperative
      radiation therapy was the strongest variable affecting QOL in patients with
      maxillectomy and prosthetic obturator reconstruction. There is further need for a
      multicenter trial with a larger sample to identify how factors affecting QOL of
      patients after maxillectomy might influence the choice of reconstruction.

PMID- 23540429
TI  - Esthetic outcome after soft tissue reconstruction of the face using deep
      dissection and composite facelift technique.
AB  - PURPOSE: Large defects in the face resulting from the excision of malignant
      tumors, trauma, and congenital malformation pose a significant challenge to
      reconstructive surgeons. Achieving good esthetic and functional outcomes is often
      very demanding. PATIENTS AND METHODS: A facelift technique was used in 47
      patients (25 female, 22 male; age range, 17.5 to 82.3 years; mean age, 49.3
      years) to replace lost tissue of the face from 2009 through 2012. The minimum
      defect size was 2 cm in diameter and the maximum was 8 cm. To achieve tension
      free coverage with a reliable blood supply, a deep-plane dissection, including
      the skin and superficial musculoaponeurotic system (SMAS), was performed. The
      deep sub-SMAS dissection was extended into the neck and the contralateral part,
      as needed. A thick flap was created and composite lifting was performed. RESULTS:
      No significant deformity concerning the lower eyelids, nose, and lip was
      registered. Most scars could be placed in hidden regions and became undetectable
      after a year. The facial nerve function remained intact in all patients.
      CONCLUSION: Using these facelift techniques, including the incision, sub-SMAS
      dissection for volumetric positioning of the skin, and the SMAS flap, the closure
      of extensive facial defects with excellent functional and esthetic results is
      conceivable.

PMID- 23540430
TI  - Application of angular measurements in the correction of the asymmetric chin.

PMID- 23540431
TI  - Palatal approach to the anterior maxillary sandwich osteotomy.
AB  - PURPOSE: This report describes a technique used to increase vertical height and
      anterior prominence of the anterior maxilla. PATIENTS AND METHODS: Two cases
      illustrate the palatal approach to segmental osteotomy with interpositional bone
      grafting (sandwich osteotomy) of the anterior maxilla. The palatal approach
      allows the segment to be moved anteriorly and inferiorly. This is in contrast to
      the buccal approach, in which the tight palatal tissue creates a vector of force
      toward the palate. The vascular pedicle for the segmental bone flap using the
      palatal approach is the labial mucosa and musculature. RESULTS: The maxillary
      alveolar ridge in case 1 was advanced 4 mm anteriorly and 5 mm inferiorly. In
      case 2, the ridge was moved 4 mm anteriorly and 6 mm inferiorly. Cases 1 and 2
      were later successfully restored with dental implants. CONCLUSION: The palatal
      approach to the anterior maxillary osteotomy was found to be effective in 2 cases
      that required anterior and inferior repositioning of the anterior maxilla.

PMID- 23540432
TI  - Fine needle aspiration of parotid tumors: diagnostic utility from a clinical
      perspective.
AB  - PURPOSE: The utility of fine needle aspiration (FNA) for parotid tumors is
      limited owing to its low diagnostic accuracy. In this study, the authors sought
      to analyze and interpret FNA results for parotid tumors from a clinical
      perspective. MATERIALS AND METHODS: Parotid tumors subjected to preoperative FNA
      and subsequent complete excision were the subject of this study. Patient
      demographics, medical records, FNA findings, and final pathology of 158
      consecutive cases were analyzed. RESULTS: The accuracy of FNA was 77.8%. The
      positive predictive value and likelihood ratio for malignancy were 90.0% and
      52.8% (95% confidence interval, 7.02-397), respectively. The positive predictive
      value and likelihood ratio for benign pathology of Warthin tumor plus pleomorphic
      adenoma were 97.8% and 7.67% (2.03-29.0), respectively. CONCLUSIONS: The FNA
      diagnosis of Warthin tumor or pleomorphic adenoma is reliable and can be safely
      regarded as a benign tumor. Based on the high positive predictive value and
      likelihood ratio, FNA of the parotid gland can offer valuable information in
      surgical planning and patient counseling in many centers.

PMID- 23540433
TI  - Simulation of colloidal fouling by coupling a dynamically updating velocity
      profile and electric field interactions with Force Bias Monte Carlo methods for
      membrane filtration.
AB  - Pressure-driven flow through a channel with membrane walls is modeled for high
      particulate volume fractions of 10%. Particle transport is influenced by Brownian
      diffusion, shear-induced diffusion, and convection due to the axial crossflow.
      The particles are also subject to electrostatic double layer repulsion and van
      der Waals attraction, from both particle-particle and particle-membrane
      interactions. Force Bias Monte Carlo (FBMC) simulations predict the deposition of
      the particles onto the membranes, where both hydrodynamics and the change in
      particle potentials determine the probability that a proposed move is accepted.
      The particle volume fraction is used to determine an apparent local viscosity
      observed by the continuum flow. As particles migrate, the crossflow velocity
      field evolves in quasi-steady fashion with each time instance appearing fully
      developed in the downstream direction. Particles subject to combined hydrodynamic
      and electric effects (electrostatic double layer repulsion and van der Waals
      attraction) reach a more stable steady-state as compared to systems with only
      hydrodynamic effects considered. As expected, at higher crossflow Reynolds
      numbers more particles remain in the crossflow free stream.

PMID- 23540434
TI  - Cataphoretic assembly of cationic dyes and deposition of carbon nanotube and
      graphene films.
AB  - Cathodic electrophoretic deposition (EPD) method has been developed for the
      fabrication of thin films from aqueous solutions of crystal violet (CV) dyes. The
      films contained rod-like particles with a long axis oriented perpendicular to the
      substrate surface. The proposed deposition mechanism involved cataphoresis of
      cationic CV(+) species, base generation in the cathodic reactions, and charge
      neutralization at the electrode surface. The assembly of rod-like particles was
      governed by pi-pi interactions of polyaromatic CV molecules. The deposition
      kinetics was studied by quartz crystal microbalance. CV dyes allowed efficient
      dispersion of multiwalled carbon nanotubes (MWCNTs) and graphene in water at
      relatively low CV concentrations. The feasibility of cathodic EPD of MWCNT and
      graphene from aqueous suspensions, containing CV, has been demonstrated. The
      deposition yield was investigated at different CV concentrations and deposition
      voltages. The relatively high deposition yield of MWCNT and graphene indicated
      that CV is an efficient dispersing, charging, and film forming agent for EPD.
      Electron microscopy data showed that at low CV concentrations in MWCNT or
      graphene suspensions and low deposition voltages, the films contained mainly
      MWCNT or graphene. The increase in the CV concentration and/or deposition voltage
      resulted in enhanced co-deposition of CV. The EPD method developed in this
      investigation paves the way for the fabrication of advanced nanocomposites by
      cathodic electrodeposition.

PMID- 23540435
TI  - Semiological evaluation of pain according to its origin: a prospective,
      observational, and national study of current French medical practice.
AB  - OBJECTIVE: To determine how the origin of acute pain influences its semiological
      characteristics, and to evaluate the efficacy and safety of two Level 2 analgesic
      combinations in general practice. RESEARCH DESIGN AND METHODS: This prospective,
      observational, multicenter study enrolled patients who consulted general
      practitioners across France for intense pain that lasted >=7 days and for which
      the physician prescribed paracetamol-codeine or paracetamol-tramadol. Completed
      physician (Day 0) and patient (Days 0-3 and Days 4-7) questionnaires provided
      data on the origin, characteristics, impact, and treatment of the pain, during
      the 7 days after the initial consultation. MAIN OUTCOME MEASURES: Pain intensity
      (0-10 unidimensional numerical scale), type (SF-MPQ) and impact on quality of
      life (QoL; SF-12). RESULTS: Overall, 1003 patient questionnaires were completed
      for Days 0-3 and 941 for Days 4-7. The origin of pain was most commonly disease
      or trauma. Mean baseline pain intensity was 7 (SD 1.3; 0-10 numerical rating
      scale), and was similar regardless of the origin. The time-course of pain
      differed according to its origin: more than two-thirds of patients with
      trauma/work accident related pain described it as being constant, whereas 43% of
      those with disease-related pain described it as recurrent/intermittent. The
      origin of pain also influenced its QoL impact: trauma/work accident related pain
      led to functional and/or professional temporary incapacity in 77% and 83% of
      patients (vs 63% for disease-related pain), while disease-related pain led to a
      change in mood and/or feeling of anxiety in 79% of patients (vs 47% [trauma] and
      58% [work accident related]). Both paracetamol-codeine and paracetamol-tramadol
      reduced pain intensity by approximately 75% and were well tolerated. Key
      limitations relate to the observational study design, countered by advantages
      gained from the 'real life' evaluation of acute pain and its treatment in a
      general medical practice setting. CONCLUSIONS: Acute pain should not be
      understood as a single entity but as multiple entities with specific
      characteristics related to its underlying origin. Furthermore, our data suggest
      that, as already demonstrated in clinical trials, Level 2 analgesia provides
      effective relief of acute pain in 'real life' conditions.

PMID- 23540436
TI  - A 6-month, prospective, observational study of PDE5 inhibitor treatment
      persistence and adherence in Middle Eastern and North African men with erectile
      dysfunction.
AB  - BACKGROUND: Erectile dysfunction (ED) negatively impacts quality of life.
      Phosphodiesterase type 5 inhibitors (PDE5Is) are effective in treating ED;
      however, rates of discontinuation remain high. OBJECTIVES: To assess on-demand
      PDE5I treatment persistence and adherence through 6 months in Middle Eastern and
      North African (MENA) men with ED in a prospective, non-interventional,
      observational trial. RESEARCH DESIGN AND METHODS: Enrolled men were >=18 years
      old from Saudi Arabia, Egypt, and the United Arab Emirates, PDE5I naive, and
      sexually active. PDE5Is were selected per routine clinical practice. Persistence
      was defined as use of >=1 dose during the prior 4 weeks, adherence as compliance
      with dosing instructions during the most recent dose. Logistic regression models
      were used to identify factors associated with persistence and adherence. MAIN
      OUTCOME MEASURES: Persistence and Adherence Questionnaire; Partner Relationship
      Questionnaire; Self-Esteem and Relationship Questionnaire; International Index of
      Erectile Function (IIEF); Erectile Dysfunction Inventory of Treatment
      Satisfaction. RESULTS: Patients' (n = 493) mean age was 49.8 years, mean BMI was
      29.3, and the majority (n = 354, 71.8%) were from Saudi Arabia. Tadalafil was the
      most prescribed PDE5I (69.6%), versus sildenafil (15.4%), or vardenafil (15.0%).
      Patients' mean IIEF-Erectile Function scores improved from moderate to mild and
      Erection Hardness Scores (SD) improved from 1.8 (1.0) at baseline to 3.5 (0.7) at
      6 months. At 6 months, 64.9% of patients were treatment persistent (tadalafil,
      68.8%, sildenafil, 65.8%, and vardenafil, 45.9%) and 59.6% were adherent. Factors
      significantly predictive (p < 0.05) of persistence at 6 months included age,
      employment status, and ED severity. Factors significantly predictive of adherence
      were age, employment status, and duration of ED. Interpretation of differences
      between drugs was limited by substantial differences in prescription rates
      between countries. CONCLUSIONS: At 6 months, 64.9% of men were treatment
      persistent. In this study, age, employment status, ED severity, and duration of
      ED were associated with persistence and/or adherence.

PMID- 23540437
TI  - Total syntheses of echinopines.
AB  - A concise and scalable synthesis of a cis-fused bicyclo[5.3.0]decane ring system
      has been developed for the total synthesis of echinopines. The core of the
      natural products was constructed efficiently through an intramolecular 1,3
      dipolar cycloaddition and ring contraction strategy.

PMID- 23540438
TI  - Cellular functions of glutathione.

PMID- 23540439
TI  - Feasibility of a "resect and watch" strategy with endoscopic resection for
      superficial pharyngeal cancer.
AB  - BACKGROUND: After endoscopic resection (ER) for superficial pharyngeal cancer
      (SPC), additional treatments such as radical surgical resection or radiation
      therapy may be needed in cases of possible incomplete resection. However, the
      benefit of prophylactic additional treatment is unclear. OBJECTIVE: To evaluate
      the feasibility of a "resect and watch" strategy with ER for SPC. DESIGN:
      Retrospective, single-center cohort study. SETTING: Tertiary cancer center.
      PATIENTS: A total of 32 patients with 47 SPCs were eligible. INTERVENTION: A
      "resect and watch" strategy of initial ER and observation until development of
      secondary diseases, including local recurrence, neck lymph node metastasis (LNM),
      and metachronous pharyngeal cancer. MAIN OUTCOME MEASUREMENTS: Complications,
      tumor recurrence, development of metachronous pharyngeal cancer, overall
      survival, and cause-specific survival. RESULTS: There were no severe
      complications related to ER. Median length of follow-up was 43 months (range, 7
      76 months). Cumulative development of secondary diseases at 5 years was 44% (95%
      CI, 24.5%-63.8%). Local recurrence (N = 4) and neck LNM (N = 5) were successfully
      treated by local resection (2 partial surgical resections and 2 additional ERs)
      and neck dissection, respectively. Metachronous pharyngeal cancers (N = 6) were
      completely removed by ER. The overall survival and cause-specific survival rates
      at 5 years were 84.4% (95% CI, 70.0%-98.8%) and 100%, respectively. No patient
      needed radical surgery as an additional therapy. Thus, the larynx and its
      function were preserved in all patients. LIMITATIONS: Retrospective nature,
      single-center setting, relatively small sample size. CONCLUSIONS: A "resect and
      watch" strategy with ER for SPC is feasible and rational.

PMID- 23540440
TI  - Pancreatoscopy-guided intracorporeal laser lithotripsy for difficult pancreatic
      duct stones: a case series with prospective follow-up (with video).

PMID- 23540441
TI  - Cyanoacrylate applications in the GI tract.

PMID- 23540443
TI  - Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with
      familial hypercholesterolemia.
AB  - OBJECTIVE: In familial hypercholesterolemia (FH), the metabolism and anti
      atherogenic functions of HDL can be affected by the continuous interactions with
      excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL
      intravascular metabolism and for HDL role in reverse cholesterol transport (RCT)
      were investigated in FH patients. METHODS: Seventy-one FH patients (39 +/- 15
      years, LDL-cholesterol=274 +/- 101; HDL-cholesterol=50 +/- 14 mg/dl) and 66
      normolipidemic subjects (NL) (38 +/- 11 years, LDL-cholesterol=105 +/- 27; HDL
      cholesterol=52 +/- 12 mg/dl) were studied. In vitro, lipid transfers were
      evaluated by incubation of plasma samples (37 degrees C, 1h) with a donor lipid
      nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol
      (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity
      was counted at the HDL fraction after chemical precipitation of apolipoprotein
      (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total
      radioactivity measured in the HDL fraction. RESULTS: Transfer of UC to HDL was
      lower in FH than in NL (5.6 +/- 2.1 vs 6.7 +/- 2.0%, p=0.0005) whereas TG (5.5 +/
      3.1 vs 3.7 +/- 0.9%, p=0.018) and PL (20.9 +/- 4.6 vs 18.2 +/- 3.7 %, p=0.023)
      transfers were higher in FH. EC transfer was equal. By multivariate analysis,
      transfers of all four lipids correlated with HDL-cholesterol and with apo A-I.
      CONCLUSION: FH elicited marked changes in three of the four tested lipid
      transfers to HDL. The entry of UC into HDL for subsequent esterification is an
      important driving force for RCT and reduction of UC transfer to HDL was
      previously associated to precocious coronary heart disease. Therefore, in FH, HDL
      functions can be lessened, which can also contribute to atherogenesis.

PMID- 23540444
TI  - Nanoscale spatial distribution of thiolated DNA on model nucleic acid sensor
      surfaces.
AB  - The nanoscale arrangement of the DNA probe molecules on sensor surfaces has a
      profound impact on molecular recognition and signaling reactions on DNA
      biosensors and microarrays. Using electrochemical atomic force microscopy, we
      have directly determined the nanoscale spatial distribution of thiolated DNA that
      are attached to gold via different methods. We discovered significant
      heterogeneity in the probe density and limited stability for DNA monolayers
      prepared by the backfilling method, that is, first exposing the surface to
      thiolated DNA then "backfilling" with a passivating alkanethiol. On the other
      hand, the monolayers prepared by "inserting" thiolated DNA into a preformed
      alkanethiol monolayer lead to a more uniformly distributed layer of DNA. With
      high-resolution images of single DNA molecules on the surface, we have introduced
      spatial statistics to characterize the nanoscale arrangement of DNA probes. The
      randomness of the spatial distribution has been characterized. By determining the
      local densities surrounding individual molecules, we observed subpopulations of
      probes with dramatically different levels of "probe crowding". We anticipate that
      the novel application of spatial statistics to DNA monolayers can enable a
      framework to understand heterogeneity in probe spatial distributions, interprobe
      interactions, and ultimately probe activity on sensor surfaces.

PMID- 23540442
TI  - Exposure of cyclosporin A in whole blood, cerebral spinal fluid, and brain
      extracellular fluid dialysate in adults with traumatic brain injury.
AB  - Cyclosporin A (CsA), an immunosuppressive medication traditionally used in the
      prevention of post-transplant rejection, is a promising neuroprotective agent for
      traumatic brain injury (TBI). Preliminary studies in animals and humans describe
      the efficacy and safety of CsA when administered following neurotrauma. The
      objective of this study is to describe CsA exposure in adults with severe TBI by
      assessing concentrations in whole blood, cerebrospinal fluid (CSF), and brain
      extracellular fluid (ECF) dialysate as measured by brain microdialysis. Severe
      TBI patients were enrolled in a randomized controlled trial following the written
      informed consent of their legal guardians. Patients received either CsA 5 mg/kg
      as a continuous infusion over 24 h, or matching placebo. Noncompartmental
      exposure analyses were performed using CsA concentrations in whole blood, CSF,
      and ECF dialysate. There were 37 patients randomized to the CsA arm of the trial
      and included in this exposure analysis. CsA was detected in the ECF dialysate and
      CSF at a fraction of the whole blood concentration. Mean CsA maximum
      concentrations were achieved at 24 and 30 h from the start of the 24 h infusion,
      in the CSF and ECF dialysate, respectively. A correlation was found between ECF
      dialysate and CSF concentrations. CsA was detected in the blood, CSF, and brain
      ECF dialysate. CsA exposure characteristic differences exist for whole blood,
      CSF, and ECF dialysate in severe TBI patients when administered as a continuous
      intravenous infusion. These exposure characteristics should be used for safer CsA
      dose optimization to achieve target CsA concentrations for neuroprotection in
      future TBI studies.

PMID- 23540445
TI  - Almanac 2012: Cell therapy in cardiovascular disease. The national society
      journals present selected research that has driven recent advances in clinical
      cardiology.
AB  - The rapid translation from bench to bedside that has been seen in the application
      of regenerative medicine to cardiology has led to exciting new advances in our
      understanding of some of the fundamental mechanisms related to human biology. The
      first generation of cells used in phase I-II trials (mainly bone marrow
      mononuclear cells) are now entering phase III clinical trials with the goal of
      producing a cell based therapeutic that can change the outcome of cardiac
      disease. First generation cell therapy appears to have addressed safety concerns
      as well as showing 'activity' in numerous published meta-analyses. With the
      knowledge gained to date, the field is moving towards the next generation of
      cells-the 'engineered' cell-that have been developed to display a phenotype that
      will further enhance the myocardial repair/salvage process. This almanac review
      covers the latest basic research that may soon have application to humans as well
      as the results of the latest clinical trials.

PMID- 23540446
TI  - Modified MuDPIT separation identified 4488 proteins in a system-wide analysis of
      quiescence in yeast.
AB  - A modified multidimensional protein identification technology (MudPIT) separation
      was coupled to an LTQ Orbitrap Velos mass spectrometer and used to rapidly
      identify the near-complete yeast proteome from a whole cell tryptic digest. This
      modified online two-dimensional liquid chromatography separation consists of 39
      strong cation exchange steps followed by a short 18.5 min reversed-phase (RP)
      gradient. A total of 4269 protein identifications were made from 4189
      distinguishable protein families from yeast during log phase growth. The "Micro"
      MudPIT separation performed as well as a standard MudPIT separation in 40% less
      gradient time. The majority of the yeast proteome can now be routinely covered in
      less than a days' time with high reproducibility and sensitivity. The newly
      devised separation method was used to detect changes in protein expression during
      cellular quiescence in yeast. An enrichment in the GO annotations "oxidation
      reduction", "catabolic processing" and "cellular response to oxidative stress"
      was seen in the quiescent cellular fraction, consistent with their long-lived
      stress resistant phenotypes. Heterogeneity was observed in the stationary phase
      fraction with a less dense cell population showing reductions in KEGG pathway
      categories of "Ribosome" and "Proteasome", further defining the complex nature of
      yeast populations present during stationary phase growth. In total, 4488
      distinguishable protein families were identified in all cellular conditions
      tested.

PMID- 23540447
TI  - Factors associated with bovine tuberculosis confirmation rates in suspect lesions
      found in cattle at routine slaughter in Great Britain, 2003-2008.
AB  - Bovine tuberculosis (bTB) is one of the most complex and intractable animal
      health problems facing the British cattle industry today. The inspection of
      carcasses from cattle sent to slaughter is part of routine surveillance for bTB
      in Great Britain (GB). Tissue with suspect lesions from cattle from herds
      previously considered uninfected with bTB is sent to the Animal Health and
      Veterinary Laboratories Agency (AHVLA) for culture and histopathological
      examination for Mycobacterium bovis infection. In this study, risk factors for
      confirmation of infection in suspect bTB lesions found at routine slaughter of
      cattle from officially bTB-free (OTF) herds in GB were investigated. The study
      sample included the first record of a suspect lesion in a bovine from any OTF
      herd identified during post-mortem inspection between 2003 and 2008. There were
      3663 submissions from 151 slaughterhouses of which 2470 (67.4%) were confirmed as
      culture positive for M. bovis. Logistic regression analysis with a random
      intercept for slaughterhouse was used to investigate relationships between bTB
      confirmation and animal and herd-level risk factors. Slaughterhouse of post
      mortem and the following factors related to bTB prevalence were significant
      predictors of confirmation probability: region of farm of origin of the animal,
      the testing interval for routine field surveillance for bTB on the farm, number
      of reactors in the last bTB incident on the farm within the last 4 years, if
      applicable, the animal's date of birth and the year of animal's slaughter. The
      modelled predicted population averaged probabilities for confirmation varied from
      0.14 to 0.90 between slaughterhouses. Differences in the detection of cattle with
      bTB between British slaughterhouses warrant further study.

PMID- 23540448
TI  - Polysubstance dependent patients display a more utilitarian profile in moral
      decision-making than alcohol-dependent patients, depressive patients and
      controls.
AB  - BACKGROUND: Addiction has been shown to be associated with the endorsement of
      utilitarian moral judgments. Ventro-medial prefrontal cortex (VMPFC) dysfunction
      may explain these findings. METHODS: 100 subjects were recruited: 25
      polysubstance dependent patients, 25 alcohol dependent patients, 25 patients with
      major depressive disorders, and 25 normal controls. Subjects were assessed with a
      battery of 24 moral dilemmas: 8 impersonal dilemmas (no physical contact
      involved); 8 personal pareto (direct action that does not make the harmed
      individual worse off) and 8 personal non-pareto (direct action that does make the
      harmed individual worse off). The Iowa Gambling Task was used to document a
      possible connection between VMPFC dysfunction and responses to the moral
      dilemmas. RESULTS: Polysubstance dependent patients endorsed more utilitarian
      choices than controls on all types of dilemmas and more than depressed patients
      on impersonal and personal pareto dilemmas. Alcohol dependent patients had
      intermediate results between polysubstance dependent patients and controls but
      these differences were not significant. All patients showed significantly poorer
      performance compared to controls on the Iowa Gambling Task, but there was no
      significant association between Iowa Gambling Tasks scores and moral dilemma
      choices. CONCLUSION: Polysubstance dependent patients made more utilitarian
      choices when responding to moral dilemmas than depressed patients and normal
      controls, while alcoholic patients showed intermediate results. The absence of
      correlation between performance on the Iowa Gambling Task and the number of more
      utilitarian choices indicates that moral dilemma and decision making under
      uncertainty tap into separate mechanisms.

PMID- 23540450
TI  - Editor's briefing.

PMID- 23540449
TI  - Concurrent choice for social interaction and amphetamine using conditioned place
      preference in rats: effects of age and housing condition.
AB  - BACKGROUND: Social interaction can serve as a natural reward that attenuates drug
      reward in rats; however, it is unknown if age or housing conditions alter the
      choice between social interaction and drug. METHODS: Individually- and pair
      housed adolescent and adult male rats were tested using conditioned place
      preference (CPP) in separate experiments in which: (1) social interaction was
      conditioned against no social interaction; (2) amphetamine (AMPH; 1mg/kg, s.c.)
      was conditioned against saline; or (3) social interaction was conditioned against
      AMPH. RESULTS: Social interaction CPP was obtained only in individually-housed
      adolescents, whereas AMPH CPP was obtained in both individually-housed
      adolescents and adults; however, the effect of AMPH was not statistically
      significant in pair-housed adults. When allowed to choose concurrently between
      compartments paired with either social interaction or AMPH, individually-housed
      adolescents preferred the compartment paired with social interaction, whereas
      pair-housed adolescents preferred the compartment paired with AMPH. Regardless of
      housing condition, adults showed a similar preference for the compartments paired
      with either social interaction or AMPH. CONCLUSIONS: Although some caution is
      needed in interpreting cross-experiment comparisons, the overall results suggest
      that individually-housed adolescents were most sensitive to the rewarding effect
      of social interaction, and this hypersensitivity to social reward effectively
      competed with AMPH reward.

PMID- 23540451
TI  - Acute kidney injury in the community: why primary care has an important role.

PMID- 23540452
TI  - Antibiotics for childhood urinary tract infection: can we be smarter?

PMID- 23540453
TI  - Emerging diagnostic technologies in primary care: what's on the horizon?

PMID- 23540454
TI  - Improving survival in colorectal cancer: what role for general practice?

PMID- 23540455
TI  - Open access publishing: important changes for the BJGP.

PMID- 23540456
TI  - Self-monitoring.

PMID- 23540457
TI  - Treatment intensification in type 2 diabetes mellitus and obesity.

PMID- 23540458
TI  - Training healthcare professionals to work with interpreters.

PMID- 23540459
TI  - HIV testing: the danger of keeping secrets.

PMID- 23540463
TI  - First do no harm: evidence sometimes shows the self-evident to be wrong.

PMID- 23540473
TI  - Duty, Kant, and deontology.

PMID- 23540474
TI  - No evidence for topical preparations in preventing stretch marks in pregnancy.

PMID- 23540475
TI  - Assumptions kill.

PMID- 23540476
TI  - 'Don't shoot the messenger': the problem of whistleblowing in general practice.

PMID- 23540477
TI  - Conservative treatment options for women with stress urinary incontinence:
      clinical update.

PMID- 23540478
TI  - Tips for GP trainees working in urology.

PMID- 23540479
TI  - Trimethoprim prescription and subsequent resistance in childhood urinary
      infection: multilevel modelling analysis.
AB  - BACKGROUND: Antibiotic resistance is a growing concern and antibiotic usage the
      main contributing factor, but there are few studies examining antibiotic use and
      resistance in children. AIM: To investigate the association between previous
      trimethoprim prescribing and resistance in urinary Escherichia coli (E. coli)
      isolates in children. DESIGN AND SETTING: Retrospective, population cohort study
      in Tayside, Scotland. METHOD: Multilevel modelling of linked microbiology and
      dispensed prescribing data for 1373 <=16-year-olds with E. coli urinary isolates
      in 2004-2009, examining the association between prior trimethoprim prescription
      and subsequent trimethoprim resistance in people with urinary E. coli isolates.
      RESULTS: Trimethoprim resistance was common (26.6%, 95% confidence interval [CI]
      = 24.6 to 28.6). Previous trimethoprim prescription was associated with
      subsequent culture of trimethoprim-resistant E. coli, with more recent
      prescription being more strongly associated with resistance. After adjusting for
      the number of previous E. coli isolates and sample year, trimethoprim prescribing
      in the previous 84 days remained significantly associated with culturing
      trimethoprim-resistant E. coli (adjusted OR 4.71, 95% CI = 1.83 to 12.16 for the
      previous 15-28 days versus never prescribed; adjusted OR 3.16, 95% CI = 1.63 to
      6.13 for the previous 29-84 days); however, associations were not statistically
      significant for longer periods since prior exposure. CONCLUSION: Trimethoprim
      prescription has implications for future resistance in individual children, as
      well as at population level. Clinicians must ensure appropriateness of treatment
      choice and duration, and alternative antibiotics should be considered for
      childhood urinary tract infections if trimethoprim has been prescribed in the
      preceding 3 months.

PMID- 23540480
TI  - Antibiotic treatment of urinary tract infection by community pharmacists: a cross
      sectional study.
AB  - BACKGROUND: Urinary tract infections (UTIs) are one of the most common conditions
      seen in female patients within primary care. Community pharmacists are familiar
      with symptomatic UTI management and supplying trimethoprim under patient group
      direction (PGD) for moderate-to-severe uncomplicated UTIs could improve patient
      access to treatment. AIM: To compare the care pathway of patients with UTI
      symptoms attending GP services with those receiving management, including
      trimethoprim supply under PGD, via community pharmacies. DESIGN AND SETTING:
      Prospective, cross-sectional, mixed methods approach in 10 community pharmacies
      within NHS Greater Glasgow and Clyde. METHOD: Pharmacies invited a purposive
      sample of female patients to participate. Pharmacists had the option of supplying
      trimethoprim under PGD to patients with moderate-to-severe infection meeting the
      PGD inclusion criteria. Data from patient (questionnaires and semi-structured
      telephone interviews) and pharmacist (questionnaires and semi-structured, face-to
      face interviews) were quantitatively and qualitatively analysed. RESULTS: Data
      were recorded on 153 patients, 97 presenting with GP prescriptions and 56
      presenting directly in the pharmacy with symptoms suggestive of UTI, of whom 41
      received trimethoprim via PGD and 15 received symptomatic management. Both GP
      adherence to local infection management guidelines and pharmacist application of
      PGD inclusion/exclusion criteria required improvement. There was demand and
      support, from patients and pharmacists, for access to antibiotic treatments for
      UTIs, without prescription, through community pharmacies. CONCLUSION: Operating
      within PGD controls, antibiotic treatments for UTIs could be provided via
      community pharmacy to improve patient access to treatment which may also maintain
      antibiotic stewardship and reduce GP workload.

PMID- 23540481
TI  - Clinical features of kidney cancer in primary care: a case-control study using
      primary care records.
AB  - BACKGROUND: Kidney cancer accounts for over 4000 UK deaths annually, and is one
      of the cancer sites with a poor mortality record compared with Europe. AIM: To
      identify and quantify all clinical features of kidney cancer in primary care.
      DESIGN: Case-control study, using General Practice Research Database records.
      METHOD: A total of 3149 patients aged >=40 years, diagnosed with kidney cancer
      between 2000 and 2009, and 14 091 age, sex and practice-matched controls, were
      selected. Clinical features associated with kidney cancer were identified, and
      analysed using conditional logistic regression. Positive predictive values for
      features of kidney cancer were estimated. RESULTS: Cases consulted more
      frequently than controls in the year before diagnosis: median 16 consultations
      (interquartile range 10-25) versus 8 (4-15): P<0.001. Fifteen features were
      independently associated with kidney cancer: visible haematuria, odds ratio 37
      (95% confidence interval [CI] = 28 to 49), abdominal pain 2.8 (95% CI = 2.4 to
      3.4), microcytosis 2.6 (95% CI = 1.9 to 3.4), raised inflammatory markers 2.4
      (95% CI = 2.1 to 2.8), thrombocytosis 2.2 (95% CI = 1.7 to 2.7), low haemoglobin
      1.9 (95% CI = 1.6 to 2.2), urinary tract infection 1.8 (95% CI = 1.5 to 2.1),
      nausea 1.8 (95% CI = 1.4 to 2.3), raised creatinine 1.7 (95% CI = 1.5 to 2.0),
      leukocytosis 1.5 (95% CI = 1.2 to 1.9), fatigue 1.5 (95% CI = 1.2 to 1.9),
      constipation 1.4 (95% CI = 1.1 to 1.7), back pain 1.4 (95% CI = 1.2 to 1.7),
      abnormal liver function 1.3 (95% CI = 1.2 to 1.5), and raised blood sugar 1.2
      (95% CI = 1.1 to 1.4). The positive predictive value for visible haematuria in
      patients aged >=60 years was 1.0% (95% CI = 0.8 to 1.3). CONCLUSION: Visible
      haematuria is the commonest and most powerful single predictor of kidney cancer,
      and the risk rises when additional symptoms are present. When considered
      alongside the risk of bladder cancer, the overall risk of urinary tract cancer
      from haematuria warrants referral.

PMID- 23540482
TI  - Temporal growth and geographic variation in the use of laboratory tests by NHS
      general practices: using routine data to identify research priorities.
AB  - BACKGROUND: Laboratory tests are extensively used for diagnosis and monitoring in
      UK primary care. Test usage by GPs, and associated costs, have grown
      substantially in recent years. AIM: This study aimed to quantify temporal growth
      and geographic variation in utilisation of laboratory tests. DESIGN AND SETTING:
      Retrospective cohort study using data from general practices in the UK. METHOD:
      Data from the General Practice Research Database, including patient demographics,
      clinical details, and laboratory test results, were used to estimate rates of
      change in utilisation between 2005 and 2009, and identify tests with greatest
      inter-regional variation, by fitting random-effects Poisson regression models.
      The study also investigated indications for test requests, using diagnoses and
      symptoms recorded in the 2 weeks before each test. RESULTS: Around 660 000 tests
      were recorded in 230 000 person-years of follow-up. Test use increased by 24.2%,
      from 23 872 to 29 644 tests per 10 000 person-years, between 2005 and 2009. Tests
      with the largest increases were faecal occult blood (121%) and C-reactive protein
      (86%). There was substantial geographic variation in test utilisation; GPs in
      some regions requested tests such as plasma viscosity and cardiac enzymes at a
      rate more than three times the national average. CONCLUSION: Increases in the use
      of laboratory tests have substantial resource implications. Rapid increases in
      particular tests may be supported by evidence-based guidelines, but these are
      often vague about who should be tested, how often, and for how long. Substantial
      regional variation in test use may reflect uncertainty about diagnostic accuracy
      and appropriate indications for the laboratory test. There is a need for further
      research on the diagnostic accuracy, therapeutic impact, and effect on patient
      health outcomes of the most rapidly increasing and geographically variable tests.

PMID- 23540483
TI  - Influence of chronic comorbidity and medication on the efficacy of treatment in
      patients with diabetes in general practice.
AB  - BACKGROUND: Evidence on the influence of comorbidity and comedication on clinical
      outcomes in patients with type 2 diabetes mellitus is scarce. AIM: To ascertain
      the effect of five chronic diseases (joint disorder, respiratory disease,
      anaemia, malignancy, depression) and three chronically used drugs (non-steroid
      anti-inflammatory drugs [NSAIDs], corticosteroids, antidepressants) on treatment
      for hypoglycaemia in patients with type 2 diabetes. DESIGN AND SETTING:
      Retrospective cohort study in a variety of practices across Flanders, Belgium.
      METHOD: A retrospective cohort study was conducted, based on data from Intego, a
      general practice-based continuous morbidity registry. Multiple logistic
      regression analysis was used to predict the change in glycosylated haemoglobin
      (HbA1c) levels related to comorbidity, comedication, and a combination of both in
      3416 patients with type 2 diabetes. Adjustments were made for age, sex, and
      diabetes-treatment group (diet, oral antidiabetic drugs, combination treatment,
      insulin). RESULTS: Concomitant joint and respiratory disorders, as well as the
      chronic use of NSAIDs and corticosteroids, either separately or in combination,
      were significantly associated with the worsening of HbA1c levels. Anaemia,
      depression, malignancy, and antidepressants had no statistically significant
      influence on the efficacy of treatment for hypoglycaemia. CONCLUSION: The
      presence of some comorbid diseases or drug use can impede the efficacy of
      treatment for type 2 diabetes. This finding supports the need to develop
      treatment recommendations, taking into account the presence of both chronic
      comorbidity and comedication. Further research must be undertaken to ascertain
      the effect other combinations of chronic diseases have on the efficacy of
      treatment of this and other diseases.

PMID- 23540484
TI  - Implications of comorbidity for primary care costs in the UK: a retrospective
      observational study.
AB  - BACKGROUND: Comorbidity is increasingly common in primary care. The cost
      implications for patient care and budgetary management are unclear. AIM: To
      investigate whether caring for patients with specific disease combinations
      increases or decreases primary care costs compared with treating separate
      patients with one condition each. DESIGN: Retrospective observational study using
      data on 86 100 patients in the General Practice Research Database. METHOD: Annual
      primary care cost was estimated for each patient including consultations,
      medication, and investigations. Patients with comorbidity were defined as those
      with a current diagnosis of more than one chronic condition in the Quality and
      Outcomes Framework. Multiple regression modelling was used to identify, for three
      age groups, disease combinations that increase (cost-increasing) or decrease
      (cost-limiting) cost compared with treating each condition separately. RESULTS:
      Twenty per cent of patients had at least two chronic conditions. All conditions
      were found to be both cost-increasing and cost-limiting when co-occurring with
      other conditions except dementia, which is only cost-limiting. Depression is the
      most important cost-increasing condition when co-occurring with a range of
      conditions. Hypertension is cost-limiting, particularly when co-occurring with
      other cardiovascular conditions. CONCLUSION: Three categories of comorbidity
      emerge, those that are: cost-increasing, mainly due to a combination of
      depression with physical comorbidity; cost-limiting because treatment for the
      conditions overlap; and cost-limiting for no apparent reason but possibly because
      of inadequate care. These results can contribute to efficient and effective
      management of chronic conditions in primary care.

PMID- 23540485
TI  - Touch in primary care consultations: qualitative investigation of doctors' and
      patients' perceptions.
AB  - BACKGROUND: Good communication skills are integral to successful doctor-patient
      relationships. Communication may be verbal or non-verbal, and touch is a
      significant component, which has received little attention in the primary care
      literature. Touch may be procedural (part of a clinical task) or expressive
      (contact unrelated to a procedure/examination). AIM: To explore GPs' and
      patients' experiences of using touch in consultations. DESIGN AND SETTING:
      Qualitative study in urban and semi-rural areas of north-west England. METHOD:
      Participating GPs recruited registered patients with whom they felt they had an
      ongoing relationship. Data were collected by semi-structured interviews and
      subjected to constant comparative qualitative analysis. RESULTS: All participants
      described the importance of verbal and non-verbal communication in developing
      relationships. Expressive touch was suggested to improve communication quality by
      most GPs and all patients. GPs reported a lower threshold for using touch with
      older patients or those who were bereaved, and with patients of the same sex as
      themselves. All patient responders felt touch on the hand or forearm was
      appropriate. GPs described limits to using touch, with some responders rarely
      using anything other than procedural touch. In contrast, most patient responders
      believed expressive touch was acceptable, especially in situations of distress.
      All GP responders feared misinterpretation in their use of touch, but patients
      were keen that these concerns should not prevent doctors using expressive touch
      in consultations. CONCLUSION: Expressive touch improves interactions between GPs
      and patients. Increased educational emphasis on the conscious use of expressive
      touch would enhance clinical communication and, hence, perhaps patient wellbeing
      and care.

PMID- 23540486
TI  - The Public Health Impact score: a new measure of public health effectiveness for
      general practices in England.
AB  - BACKGROUND: Health policy in the UK is increasingly focused on the measurement of
      outcomes rather than structures and processes of health care. AIM: To develop a
      measure of the effectiveness of primary care in terms of population health
      outcomes. DESIGN AND SETTING: A cross-sectional study of general practices in
      England. METHOD: Twenty clinical quality of care indicators for which there was
      evidence of mortality reduction were identified from the national Quality and
      Outcomes Framework (QOF) pay-for-performance scheme. The number of lives saved by
      8136 English practices (97.97% of all practices) in 2009/2010 was estimated,
      based on their performance on these measures, and a public health impact measure,
      the PHI score, was constructed. Multilevel regression models were used to
      identify practice and population predictors of PHI scores. RESULTS: The mean
      estimated PHI score was 258.9 (standard deviation [SD] = 73.3) lives saved per
      100 000 registered patients, per annum. This represents 75.7% of the maximum
      potential PHI score of 340.9 (SD = 91.8). PHI and QOF scores were weakly
      correlated (Pearson r = 0.28). The most powerful predictors of PHI score were the
      prevalence of the relevant clinical conditions (beta = 0.77) and the proportion
      of patients aged >=65 years (beta = 0.22). General practices that were less
      successful at achieving their maximum potential PHI score were those with a lower
      prevalence of relevant conditions (beta = 0.29), larger list sizes (beta = 
      0.16), greater area deprivation (beta = -0.15), and a larger proportion of
      patients aged >=65 years (beta = -0.13). CONCLUSION: The PHI score is a potential
      alternative metric of practice performance, measuring the estimated mortality
      reduction in the registered population. Rewards under the QOF pay-for-performance
      scheme are not closely aligned to the public health impact of practices.

PMID- 23540487
TI  - General practice by numbers: presentation to final outcome.

PMID- 23540488
TI  - In vitro antiviral activity of hypothiocyanite against A/H1N1/2009 pandemic
      influenza virus.
AB  - Influenza virus spreads via small particle aerosols, droplets and fomites, and
      since it can survive for a short time on surfaces, can be introduced into the
      nasal mucosa before it loses infectivity. The hypothiocyanite ion (OSCN-),
      product of the lactoperoxidase/H2O2/SCN- system of central airways, is emerging
      as an important molecule for innate defense mechanism against bacteria, fungi and
      viruses. Here we demonstrated that OSCN(-) displays virucidal activity in vitro
      against the A/H1N1 2009 pandemic influenza virus. The concentration required to
      inhibit viral replication by 50% was 2 MUM when virus were challenged directly
      with OSCN- before cell inoculation. These values were even lower when inoculated
      cells were maintained in contact with enzyme free-OSCN- in the culture medium.
      The last experimental conditions better reflect those of tracheobronchial mucosa,
      where HOSCN/OSCN- is retained in the air-liquid interface and inactivates both
      the viruses approaching the epithelium from outside and those released from the
      inoculated cells after the replication cycle. Importantly no OSCN- cytotoxicity
      was observed in the cellular system employed. The lack of toxicity in humans and
      the absence of damage on surfaces of fomites suggest a potential use of OSCN- to
      avoid mucosal and environmental transmission of influenza virus. Since
      hypothiocyanite is normally present in human airways a low risk of viral
      resistance is envisaged. In vivo confirmatory studies are needed to evaluate the
      appropriate dose, regimen and formulation.

PMID- 23540489
TI  - Toxicogenomic approaches for understanding molecular mechanisms of heavy metal
      mutagenicity and carcinogenicity.
AB  - Heavy metals that are harmful to humans include arsenic, cadmium, chromium, lead,
      mercury, and nickel. Some metals or their related compounds may even cause
      cancer. However, the mechanism underlying heavy metal-induced cancer remains
      unclear. Increasing data show a link between heavy metal exposure and aberrant
      changes in both genetic and epigenetic factors via non-targeted multiple
      toxicogenomic technologies of the transcriptome, proteome, metabolome, and
      epigenome. These modifications due to heavy metal exposure might provide a better
      understanding of environmental disorders. Such informative changes following
      heavy metal exposure might also be useful for screening of biomarker-monitored
      exposure to environmental pollutants and/or predicting the risk of disease. We
      summarize advances in high-throughput toxicogenomic-based technologies and
      studies related to exposure to individual heavy metal and/or mixtures and propose
      the underlying mechanism of action and toxicant signatures. Integrative multi
      level expression analysis of the toxicity of heavy metals via system toxicology
      based methodologies combined with statistical and computational tools might
      clarify the biological pathways involved in carcinogenic processes. Although
      standard in vitro and in vivo endpoint testing of mutagenicity and
      carcinogenicity are considered a complementary approach linked to disease, we
      also suggest that further evaluation of prominent biomarkers reflecting effects,
      responses, and disease susceptibility might be diagnostic. Furthermore, we
      discuss challenges in toxicogenomic applications for toxicological studies of
      metal mixtures and epidemiological research. Taken together, this review presents
      toxicogenomic data that will be useful for improvement of the knowledge of
      carcinogenesis and the development of better strategies for health risk
      assessment. 

PMID- 23540490
TI  - Stereotactic body radiation therapy planning with duodenal sparing using
      volumetric-modulated arc therapy vs intensity-modulated radiation therapy in
      locally advanced pancreatic cancer: a dosimetric analysis.
AB  - Stereotactic body radiation therapy (SBRT) achieves excellent local control for
      locally advanced pancreatic cancer (LAPC), but may increase late duodenal
      toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated
      radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams.
      This study dosimetrically evaluates the feasibility of implementing duodenal
      constraints for SBRT using VMAT vs IMRT. Non-duodenal sparing (NS) and duodenal
      sparing (DS) VMAT and IMRT plans delivering 25Gy in 1 fraction were generated for
      15 patients with LAPC. DS plans were constrained to duodenal Dmax of<30Gy at any
      point. VMAT used 1 360 degrees  coplanar arc with 4 degrees  spacing between
      control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at
      40 degrees  angles. Dosimetric parameters for target volumes and organs at risk
      were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample
      Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly
      reduced duodenal Dmean, Dmax, D1cc, D4%, and V20Gy compared with NS plans (all
      p<=0.002). DS constraints compromised target coverage for IMRT as demonstrated by
      reduced V95% (p = 0.01) and Dmean (p = 0.02), but not for VMAT. DS constraints
      resulted in increased dose to right kidney, spinal cord, stomach, and liver for
      VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in
      sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was
      superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT
      required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes
      faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning
      for LAPC can significantly reduce duodenal point or volumetric dose parameters
      for both VMAT and IMRT. The primary consequence of implementing DS constraints
      for VMAT is increased dose to other organs at risk, whereas for IMRT it is
      compromised target coverage. These findings suggest clinical situations where
      each technique may be most useful if DS constraints are to be employed. 

PMID- 23540491
TI  - Dosimetric effects of weight loss or gain during volumetric modulated arc therapy
      and intensity-modulated radiation therapy for prostate cancer.
AB  - Weight loss or gain during the course of radiation therapy for prostate cancer
      can alter the planned dose to the target volumes and critical organs. Typically,
      source-to-surface distance (SSD) measurements are documented by therapists on a
      weekly basis to ensure that patients' exterior surface and isocenter-to-skin
      surface distances remain stable. The radiation oncology team then determines
      whether the patient has undergone a physical change sufficient to require a new
      treatment plan. The effect of weight change (SSD increase or decrease) on
      intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy
      (VMAT) dosimetry is not well known, and it is unclear when rescanning or
      replanning is needed. The purpose of this study was to determine the effects of
      weight change (SSD increase or decrease) on IMRT or VMAT dose delivery in
      patients with prostate cancer and to determine the SSD change threshold for
      replanning. Whether IMRT or VMAT provides better dose stability under weight
      change conditions was also determined. We generated clinical IMRT and VMAT
      prostate and seminal vesicle treatment plans for varying SSDs for 10 randomly
      selected patients with prostate cancer. The differences due to SSD change were
      quantified by a specific dose change for a specified volume of interest. The
      target mean dose, decreased or increased by 2.9% per 1-cm SSD decrease or
      increase in IMRT and by 3.6% in VMAT. If the SSD deviation is more than 1cm, the
      radiation oncology team should determine whether to continue treatment without
      modifications, to adjust monitor units, or to resimulate and replan. 

PMID- 23540492
TI  - Maximizing dosimetric benefits of IMRT in the treatment of localized prostate
      cancer through multicriteria optimization planning.
AB  - We examine the quality of plans created using multicriteria optimization (MCO)
      treatment planning in intensity-modulated radiation therapy (IMRT) in treatment
      of localized prostate cancer. Nine random cases of patients receiving IMRT to the
      prostate were selected. Each case was associated with a clinically approved plan
      created using Corvus. The cases were replanned using MCO-based planning in
      RayStation. Dose-volume histogram data from both planning systems were presented
      to 2 radiation oncologists in a blinded evaluation, and were compared at a number
      of dose-volume points. Both physicians rated all 9 MCO plans as superior to the
      clinically approved plans (p<10(-5)). Target coverage was equivalent (p = 0.81).
      Maximum doses to the prostate and bladder and the V50 and V70 to the anterior
      rectum were reduced in all MCO plans (p<0.05). Treatment planning time with MCO
      took approximately 60 minutes per case. MCO-based planning for prostate IMRT is
      efficient and produces high-quality plans with good target homogeneity and
      sparing of the anterior rectum, bladder, and femoral heads, without sacrificing
      target coverage. 

PMID- 23540493
TI  - Establishing an optimized patient-specific verification program for volumetric
      modulated arc therapy.
AB  - Quality assurance (QA) of volumetric modulated arc therapy (VMAT) increases the
      workload significantly. We compared the results from 4 verification methods to
      establish an efficient VMAT QA. Planning for VMAT treatments was carried out for
      40 consecutive patients. Pretreatment verifications were carried out with ion
      chamber array Physikalish-Technische Werkstatten (PTW729), electronic portal
      dosimetry (EPID), ion chamber measurements, and independent dose calculation with
      Diamond program. 2D analyses were made using the gamma analysis (3mm distance to
      agreement and 3% dose difference relative to maximum, 10% dose threshold).
      Average point dose difference calculated by Eclipse relative to ion chamber
      measurements and Diamond were 0.1%+/-0.9% and 0.6%+/-2.2%, respectively. Average
      pass rate for PTW729 was 99.2%+/-1.9% and 98.3%+/-1.3% for EPID. The total
      required time (linac occupancy time given in parentheses) for each QA method was:
      PTW729 43.5 minutes (26.5 minutes), EPID 14.5 minutes (2.5 minutes), ion chamber
      34.5 minutes (26.5 minutes), and Diamond 12.0 minutes (0 minute). The results
      were consistent and allowed us to establish an optimized protocol, considering
      safety and accuracy as well as workload, consisting of 2 verification methods:
      EPID 2D analysis and independent dose calculation. 

PMID- 23540494
TI  - Feasibility of an online adaptive replanning method for cranial frameless
      intensity-modulated radiosurgery.
AB  - To introduce an approach for online adaptive replanning (i.e., dose-guided
      radiosurgery) in frameless stereotactic radiosurgery, when a 6-dimensional (6D)
      robotic couch is not available in the linear accelerator (linac). Cranial
      radiosurgical treatments are planned in our department using intensity-modulated
      technique. Patients are immobilized using thermoplastic mask. A cone-beam
      computed tomography (CBCT) scan is acquired after the initial laser-based patient
      setup (CBCTsetup). The online adaptive replanning procedure we propose consists
      of a 6D registration-based mapping of the reference plan onto actual CBCTsetup,
      followed by a reoptimization of the beam fluences ("6D plan") to achieve similar
      dosage as originally was intended, while the patient is lying in the linac couch
      and the original beam arrangement is kept. The goodness of the online adaptive
      method proposed was retrospectively analyzed for 16 patients with 35 targets
      treated with CBCT-based frameless intensity modulated technique. Simulation of
      reference plan onto actual CBCTsetup, according to the 4 degrees of freedom,
      supported by linac couch was also generated for each case (4D plan). Target
      coverage (D99%) and conformity index values of 6D and 4D plans were compared with
      the corresponding values of the reference plans. Although the 4D-based approach
      does not always assure the target coverage (D99% between 72% and 103%), the
      proposed online adaptive method gave a perfect coverage in all cases analyzed as
      well as a similar conformity index value as was planned. Dose-guided radiosurgery
      approach is effective to assure the dose coverage and conformity of an
      intracranial target volume, avoiding resetting the patient inside the mask in a
      "trial and error" way so as to remove the pitch and roll errors when a robotic
      table is not available. 

PMID- 23540495
TI  - Genetic determinants of cholestasis.
AB  - Cholestasis is an overarching term applied for conditions whereby biliary
      constituents are found in the circulation because of impairment to bile flow. A
      variety of processes can lead to cholestasis, be they acute or chronic injuries
      to hepatocytes, cholangiocytes, or the broader biliary tree itself. Such injuries
      may be driven by rare but highly informative primary genetic abnormalities, or
      may be seen in individuals with a prior genetic predisposition when confronted by
      specific environmental challenges such as drug exposure. This review provides a
      broad outline of some fundamental primary genetic cholestatic syndromes and an
      update on varying genetic predisposition underlying several acquired cholestatic
      processes.

PMID- 23540497
TI  - Drug-induced cholestasis.
AB  - Cholestasis caused by drugs is an important differential diagnosis in patients
      presenting with a biochemical cholestatic pattern. The extent of serologic tests
      and radiological imaging depends on the clinical context. The underlying
      condition of the patient and detailed information on drug use, results of
      rechallenge, and the documented hepatotoxicity of the drug are important to
      establish a diagnosis of drug-induced liver injury (DILI). Most cases of
      cholestatic DILI are mild, but in rare cases, ductopenia and cholestatic
      cirrhosis can develop. Approximately 10% of patients with cholestatic jaundice
      caused by drugs develop liver failure.

PMID- 23540498
TI  - Primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver
      disease characterized by multifocal strictures of intra and extrahepatic bile
      ducts. PSC occurs more commonly in men and is often associated with inflammatory
      bowel disease. At present, there is no effective medical therapy for PSC. Current
      management of patients with PSC is centered on endoscopic therapy of biliary
      strictures, management of complications of chronic cholestasis and of progressive
      liver disease, and close clinical monitoring for development of
      cholangiocarcinoma, as well as for timely referral for liver transplantation.

PMID- 23540499
TI  - Primary biliary cirrhosis: therapeutic advances.
AB  - Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic
      liver disease characterized by destruction of the interlobular bile ducts, which,
      if untreated, leads to fibrosis, biliary cirrhosis, and liver failure. Because
      liver transplantation remains the only curative option for PBC, the goals of
      treatment are to slow the rate of progression, to alleviate related symptoms, and
      to prevent complications. Ursodeoxycholic acid is the only US Food and Drug
      Administration-approved medical treatment of PBC. Several agents are undergoing
      evaluation as monotherapy or as an adjuvant to ursodeoxycholic acid. This review
      summarizes current therapeutic advances in the care of patients with PBC.

PMID- 23540500
TI  - Cholestatic liver disease overlap syndromes.
AB  - Primary biliary cirrhosis and primary sclerosing cholangitis share some clinical
      features with autoimmune hepatitis, but when features of autoimmune hepatitis are
      present, prognosis can be affected and immunosuppressive treatment warranted. The
      presence of severe interface hepatitis in primary biliary cirrhosis portends a
      worse prognosis and should prompt evaluation for possible autoimmune hepatitis
      overlap and treatment with immunosuppression. Specific models to identify which
      subjects benefit most from the addition of immunosuppression need to be
      developed. Drug-induced liver injury and IgG4 disease may masquerade as
      autoimmune hepatitis or primary sclerosing cholangitis and are important to
      consider in the differential diagnosis of the overlap or variant syndromes.

PMID- 23540501
TI  - IgG4-associated cholangitis.
AB  - IgG4-associated cholangitis is the hepatobiliary manifestation of a recently
      characterized inflammatory systemic disease, associated with increased IgG4 serum
      levels and IgG4-positive lymphoplasmacytic infiltration. Often, patients present
      with obstructive jaundice, and imaging reveals stenoses of the extrahepatic or
      intrahepatic bile ducts, often in association with parenchymal pancreatic
      findings and irregularities of the pancreatic duct. The histologic findings
      include lymphoplasmacytic infiltrates, on occasion resulting in tumefactive
      lesions (which can mimic malignancy), obliterative phlebitis, and fibrotic
      changes. Steroid treatment is the mainstay of management, but relapse is common
      after discontinuation of therapy or during tapering of steroids and may require
      further treatment.

PMID- 23540496
TI  - Nuclear receptors as drug targets in cholestatic liver diseases.
AB  - Cholestatic liver diseases encompass a wide spectrum of disorders with different
      causes, resulting in impaired bile flow and accumulation of bile acids and other
      potentially hepatotoxic cholephils. The understanding of the molecular mechanisms
      of bile formation and cholestasis has recently improved significantly through new
      insights into nuclear receptor (patho)biology. Nuclear receptors are ligand
      activated transcription factors, which act as central players in the regulation
      of genes responsible for elimination and detoxification of biliary constituents
      accumulating in cholestasis. They also control other pathophysiologic processes
      such as inflammation, fibrogenesis, and carcinogenesis involved in the
      pathogenesis and disease progression of cholestasis liver diseases.

PMID- 23540502
TI  - Secondary sclerosing cholangitis: pathogenesis, diagnosis, and management.
AB  - Secondary sclerosing cholangitis (SSC) is an aggressive and rare disease with
      intricate pathogenesis and multiple causes. Understanding the specific cause
      underlying each case of SSC is crucial in the clinical management of the disease.
      Radiologic imaging can help diagnose SSC and hence institute management in a
      timely manner. Management may encompass simple interventions, such as supportive
      therapy, antibiotics, and monitoring, or more serious measures, such as surgery,
      endoscopic intervention, or liver transplantation. Patients with AIDS
      cholangiopathy have limited therapeutic options and worsened survival. The
      disease should always be highly suspected in patients with primary sclerosing
      cholangitis with questionable diagnosis.

PMID- 23540503
TI  - Alagille syndrome and other hereditary causes of cholestasis.
AB  - Neonatal conjugated jaundice is a common presentation of hereditary liver
      diseases, which, although rare, are important to recognize early. Developments in
      molecular genetic techniques have enabled the identification of causative genes,
      which has improved diagnostic accuracy for patients and has led to a greater
      understanding of the molecular pathways involved in liver biology and
      pathogenesis of liver diseases. This review provides an update of the current
      understanding of clinical and molecular features of the inherited liver diseases
      that cause neonatal conjugated jaundice.

PMID- 23540505
TI  - Advances in pathogenesis and treatment of pruritus.
AB  - The pathogenesis of itch during cholestasis is largely unknown and treatment
      options are limited. Lysophosphatidate, female steroid hormones, and endogenous
      opioids are among the agents discussed as potential pruritogens in cholestasis.
      The itch-alleviating action of guideline-based therapeutic interventions with
      anion exchanger resins, rifampicin, opioid antagonists, and serotonin reuptake
      inhibitors are studied to unravel the molecular pathogenesis of itch. Still, a
      considerable part of the patients is in need of alternative experimental
      therapeutic approaches (eg, UV-B phototherapy, extracorporeal albumin dialysis,
      nasobiliary drainage), providing additional information about the enigmatic
      pathophysiology of cholestatic pruritus.

PMID- 23540504
TI  - Systemic causes of cholestasis.
AB  - Systemic causes of cholestasis constitute a diverse group of diseases across
      organ systems. The pathophysiology of cholestasis in systemic disease can be a
      consequence of direct involvement of a disease process within the liver or
      extrahepatic biliary system or secondary to immune-mediated changes in bile flow.
      Evaluating a patient with cholestasis for a systemic cause requires an
      understanding of the patient's risk factors, clinical setting (eg, hospitalized
      or immunosuppressed patient), clinical features, and pattern of laboratory
      abnormalities.

PMID- 23540506
TI  - Care of the cholestatic patient.
AB  - Cholestasis is defined as impairment of bile formation or bile flow. Care of the
      patient with cholestatic features is dependent on identifying the cause of the
      cholestasis, initiating appropriate treatment of reversible conditions, and the
      recognition and management of cholestasis-specific complications. Cholestasis may
      include extrahepatic ducts and intrahepatic bile ducts, or may be limited to one
      or the other. Jaundice and pruritus are the hallmarks of cholestasis clinically
      but biochemical evidence may, and often does, precede the clinical
      manifestations.

PMID- 23540507
TI  - Liver transplant for cholestatic liver diseases.
AB  - Cholestatic liver diseases include a group of diverse disorders with different
      epidemiology, pathophysiology, clinical course, and prognosis. Despite
      significant advances in the clinical care of patients with cholestatic liver
      diseases, liver transplant (LT) remains the only definitive therapy for end-stage
      liver disease, regardless of the underlying cause. As per the United Network for
      Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease
      was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the
      available evidence on various common and rare cholestatic liver diseases, disease
      specific issues, and pertinent aspects of LT.

PMID- 23540508
TI  - Cholestatic liver diseases.

PMID- 23540510
TI  - Molecular dynamics simulation of the solid-state topochemical polymerization of
      S2N2.
AB  - Molecular dynamics simulations of the solid-state topochemical polymerization of
      four-membered S2N2 rings to (SN)x have been presented by involving DFT methods
      and periodic functions. Isotropic pressure compression and a slightly elevated
      temperature have been applied to lower the activation barriers and to increase
      the rate of the reaction to be within the framework of MD simulations. The
      polymer formation is initiated by the cleavage of one bond in one S2N2 ring with
      a virtually instantaneous attack of the fragment thus formed on the neighboring
      ring. The energetically most-favored reaction then quickly propagates along a
      axis throughout the lattice. The structures of the polymer chains are in good
      agreement with that observed experimentally in the crystal structure
      determination, but there is less long-range order between the neighboring chains.
      Upon polymerization the packing of the molecules changes from the herringbone
      structure of the S2N2 lattice to a layered structure in the (SN)x lattice. While
      not the same, the simulated and experimental packing changes bear a qualitative
      similarity. The simulated polymerization was also observed to propagate along c
      axis in addition to a axis, but these side effects generally disappear toward the
      end of the simulations. In some cases, the polymers propagating simultaneously in
      both a and c axis directions persist at the end of the simulation resulting in a
      complicated network of sulfur-nitrogen chains. This finds experimental support in
      the observation of several polymorphs (SN)x with severe disorder in the lattice.

PMID- 23540511
TI  - Discrimination of ST deviation caused by acute coronary occlusion from normal
      variants and other abnormal conditions, using computed electrocardiographic
      imaging based on 12-lead ECG.
AB  - BACKGROUND: Many graphical methods for displaying ST-segment deviation in the ECG
      have been tried for enhancing decision-making in patients with suspected acute
      coronary syndromes. Computed electrocardiographic imaging (CEI), based on a
      mathematical inverse solution, has been recently applied to transform ST-J point
      measurements made in conventional 12-lead ECG into a display of epicardial
      potentials in bull's-eye format. The purpose of this study is to assess utility
      of CEI in the clinical setting. METHODS: In 99 patients with stable coronary
      disease, 12-lead ECGs were recorded during elective percutaneous coronary
      intervention (PCI), first before balloon-catheter insertion and then when an
      intracoronary balloon blocked blood supply to a region of myocardium for more
      than 4minutes (typically 5minutes). Four groups of patients were additionally
      studied, namely those with preexcitation, pericarditis, early repolarization
      syndrome (ERS), and left ventricular hypertrophy (LVH) with strain. Comparisons
      between performances of published criteria for ST-elevation myocardial infarction
      (STEMI) and quantitative as well as visual assessment of CEI images were based on
      sensitivities and specificities. RESULTS: Visual assessment of CEI outperformed
      STEMI criteria. This was especially evident for the capability of detecting LCx
      occlusion with sensitivities for STEMI criteria=35% and for visual assessment of
      CEI by 2 physicians=71%, i. e. twice as many patients were correctly identified
      by CEI. False positive rates for CEI were low in patients with LVH with strain as
      well as with preexcitation for both methods. For pericarditis and ERS, visual as
      well as quantitative assessment of CEI performed better than STEMI criteria.
      CONCLUSION: Visual assessment of CEI is a promising method for increasing the
      accuracy of ECG-based triage to PCI or conservative care.

PMID- 23540513
TI  - Ir(I)-catalyzed synthesis of N-substituted pyridones from 2-alkoxypyridines via C
      O bond cleavage.
AB  - A cationic Ir(I) complex-catalyzed O-to-N-alkyl migration in 2-alkoxypyridines
      bearing a secondary alkyl group on the oxygen atom by C-O bond cleavage is
      described. The present transformation gave various N-alkylpyridones in moderate
      to good yields. The addition of sodium acetate played a key role in suppressing
      beta-hydrogen elimination.

PMID- 23540512
TI  - Opioid switching from and to tapentadol extended release in cancer patients:
      conversion ratio with other opioids.
AB  - OBJECTIVES: The aim of this exploratory study was to assess the conversion ratios
      between tapentadol and other opioids in patients requiring an opioid switching.
      METHODS: A prospective study was carried out in a convenience sample of
      consecutive patients admitted to an acute palliative care unit and a home care
      unit for a period of 1 year. Patients who were switched from/to tapentadol were
      selected. The initial ratio between tapentadol and other opioids, expressed as
      oral morphine equivalents was 1:3.3. The subsequent doses were flexible and were
      changed to fit the patients' needs. Pain intensity and distress score were
      recorded until opioid doses were stable. In all, 37 patients were examined; 24
      and 13 patients were switched from and to tapentadol, respectively. RESULTS: The
      most frequent sequences were tapentadol-morphine (18 patients) in one direction,
      and morphine-tapentadol (8 patients) in the other direction. In the sequence
      tapentadol-morphine and morphine-tapentadol, the mean final tapentadol-morphine
      ratios were 3.9:1 (SD 2.3), and 1:4.5 (SD 3.2), respectively, which did not
      differ significantly from the initial established conversion ratio. A minority of
      patients were switched from/to tapentadol to/from other opioids. Globally, the
      initial ratio did not change after switching took place. CONCLUSION: Data suggest
      that a conversion ratio between tapentadol and other opioids, expressed in oral
      morphine equivalents could be 1:3.3 in both direction, particularly in patients
      who are switched in conditions of equianalgesia. The limited number of patients
      prevents a definitive conclusion to be drawn, and data should be interpreted with
      caution, given the exploratory nature of the study and the question of the low
      number of patients should be addressed in future studies.

PMID- 23540514
TI  - Unprecedented challenges.

PMID- 23540515
TI  - Addressing methodological and ethical challenges of qualitative health research
      on persons with schizophrenia and bipolar disorder.
AB  - Qualitative studies of persons with schizophrenia and bipolar disorder may affect
      clinical practice and social policy. However, methodological and ethical
      challenges may present during studies of persons with these specific mental
      illnesses. The purpose of this paper is to increase transparency about how
      researchers addressed these challenges during a recent grounded theory study
      about engagement in primary care. As the researchers addressed the challenges,
      they increased understanding about persons with schizophrenia and bipolar
      disorder. They also gained insight about the challenges of studying persons with
      these specific mental illnesses and about the rigor and credibility of
      qualitative methods.

PMID- 23540516
TI  - Female families' experiences of caring for persons with schizophrenia.
AB  - The caring experiences of female families of persons with schizophrenia were
      described through exploring the families' descriptions of their experiences.
      Focus group interviews were conducted with 11 family caregivers. According to
      content analysis, the experiences revealed five major themes: early family
      experiences, family perceptions of illness and relatives with schizophrenia,
      family burden and suffering, family attitudes toward relatives with
      schizophrenia, and family thoughts about society and mental health resources.
      Also, the families had strength to overcome considerable adversity. It is needed
      for professionals to listen to family caregivers' narratives carefully and
      improve the support by focusing on accepting their experiences and histories with
      persons with schizophrenia.

PMID- 23540517
TI  - Pushing the boundaries: understanding self-harm in a non-clinical population.
AB  - This study investigates 122 people's descriptions of their self-harm experiences
      using thematic analysis. Analysis revealed four themes: What counts as self-harm,
      What leads to self-harm, Intentions and Managing stigma. Our participants
      challenged commonly accepted understandings in terms of method, outcome and
      intentions. Several difficulties associated with discriminating between suicidal
      and non-suicidal self-harm were highlighted, which may be important in clinical
      practice. Few participants mentioned diagnosed psychiatric disorders; they best
      understood self-harm through their social experiences. Focusing on social
      understandings of self-harm may help reduce associated stigma and barriers to
      help-seeking.

PMID- 23540518
TI  - An evaluation of an online peer support forum for university students with
      depressive symptoms.
AB  - BACKGROUND: Depression is the most common mental health problem among young
      people, particularly university students, with prevalence rates as high as 48%
      reported. This population however, is reluctant to seek professional help. Online
      interventions may be particularly appealing to students, with evidence suggesting
      that they use the Internet for mental health support. While there are many mental
      health resources on the Internet few focus specifically on the needs of young
      people and few have been evaluated. This research aimed to develop and pilot test
      an online peer support intervention for students experiencing depressive
      symptoms. METHODS: A depression support Web site (www.losetheblues.ie) was
      designed specifically for 18-24 year old students. The study used a mixed method,
      involving quantitative descriptive, pre- and post-test and qualitative
      descriptive designs. Data were collected using the Centre for Epidemiological
      Studies Depression Scale (CES-D), a background questionnaire and online forum
      posts. RESULTS: The sample consisted of 117 university students with self
      reported depressive symptoms. Results from participants in the pre- and post-test
      element of the study, showed no statistical significance. The forum posts
      revealed that the participants' main difficulties were loneliness and perceived
      lack of socialization skills. The Web site provided a place for sharing, offering
      and receiving emotional and informational support. CONCLUSION: Developing health
      care interventions in an online environment presents unique challenges to the
      research process, however they have the potential to provide mental health care
      that is accessible and affordable.

PMID- 23540519
TI  - Web recruitment and internet use and preferences reported by women with
      postpartum depression after pregnancy complications.
AB  - Nearly one million women each year have pregnancy complications that cause
      antepartum and postpartum anxiety and depression. This exploratory study
      determined 1) feasibility of using social media to recruit women with depressive
      symptoms following high risk pregnancy, 2) women's barriers to treatment, 3) use
      of online resources for assistance with PPD, and 4) preferences for internet
      treatment. Among a national sample of 53 women, nearly 70% had major depression.
      Common barriers were lack of time and stigma. Over 90% of women would use the
      internet to learn coping strategies for PPD. Women expressed interest in web
      based PPD treatment and identified desired characteristics of an intervention.

PMID- 23540520
TI  - Psychometric assessment of the depressive cognition scale among caregivers of
      persons with autism spectrum disorder.
AB  - Caregivers of persons with autism spectrum disorders (ASD) are prone to
      depression, and early identification of cognitive depressive symptoms is
      important to prevent the development of clinical depression. The Depressive
      Cognition Scale (DCS) can be used for early detection, but the scale's
      psychometrics has not been tested in caregivers of persons with ASD. In this
      study, 95 caregivers of persons with ASD completed the eight-item DCS and
      measures of caregiver burden and resourcefulness. A Cronbach's alpha of .90
      indicated internal consistency. Construct validity was supported by significant
      correlations with caregiver burden (.59) and resourcefulness (-.57). Principal
      component factor analysis produced a single factor with 58% of the variance
      explained. The findings suggest the DCS is useful for early detection of
      depression in caregivers of persons with ASD.

PMID- 23540521
TI  - Effect of domain-specific life satisfaction on depressive symptoms in late
      adulthood and old age: results of a cross-sectional descriptive survey.
AB  - PURPOSE: The aim of this study was to determine the effect of domain-specific
      life satisfaction on the risk of depressive symptoms in late adulthood and old
      age. METHODS: A cross-sectional descriptive survey was conducted using stratified
      data from the Korean Longitudinal Study of Aging (KLoSA). The respondents
      completed the Korean version CES-D and domain-specific life satisfaction.
      RESULTS: In both groups, satisfaction with health and economic status were
      significant predictors of depressive symptoms. In the old age group, depressive
      symptoms were also predicted by satisfaction with the relationships with one's
      spouse and with one's children. CONCLUSION: Life satisfaction was a crucial
      predictive factor for depressive symptoms in late adulthood and old age.

PMID- 23540522
TI  - Electronic medical/health record and pediatric behavioral health providers:
      progress and problems.

PMID- 23540523
TI  - Photobias instability of high performance solution processed amorphous zinc tin
      oxide transistors.
AB  - The effects of the annealing temperature on the structural and chemical
      properties of soluble-processed zinc-tin-oxide (ZTO) films were examined by
      transmission electron microscopy, atomic force microscopy, high resolution X-ray
      reflectivity, and X-ray photoelectron spectroscopy. The density and purity of the
      resulting ZTO channel layer increased with increasing annealing temperature,
      whereas the oxygen vacancy defect density decreased. As a result, the device
      performance of soluble ZTO thin film transistors (TFTs) was improved at higher
      annealing temperature. Although the 300  degrees C-annealed ZTO TFT showed a
      marginal field-effect mobility (MUFE) and high threshold voltage (Vth) of 0.1
      cm(2)/(V s) and 7.3 V, respectively, the 500  degrees C-annealed device exhibited
      a reasonably high MUFE, low subthreshold gate swing (SS), Vth, and Ion/off of 6.0
      cm(2)/(V s), 0.28 V/decade, 0.58 V, and 4.0 * 10(7), respectively. The effects of
      dark negative bias stress (NBS) and negative bias illumination stress (NBIS) on
      the degradation of transfer characteristics of ZTO TFTs were also investigated.
      The instability of Vth values of the ZTO TFTs under NBS and NBIS conditions was
      suppressed with increasing annealing temperature. To better understand the charge
      trapping mechanism, the dynamics of Vth shift with NBS and NBIS time for all ZTO
      TFTs was analyzed on the basis of the stretched exponential relaxation. The
      negative Vth shift for each transistor was accelerated under NBIS conditions
      compared to NBS, which resulted in a higher dispersion parameter and smaller
      relaxation time for NBIS degradation. The relaxation time for NBS and NBIS
      instability increased with increasing annealing temperature, which is discussed
      on the basis of the transition mechanism of oxygen vacancy defects.

PMID- 23540524
TI  - Skull thickening, paranasal sinus expansion, and sella turcica shrinkage from
      chronic intracranial hypotension.
AB  - In children or young adults, the morphology of the skull can be altered by
      excessive drainage of CSF following placement of a ventriculoperitoneal (VP)
      shunt. In Sunken Eyes, Sagging Brain Syndrome, gradual enlargement of the orbital
      cavity occurs from low or negative intracranial pressure (ICP), leading to
      progressive bilateral enophthalmos. The authors report several heretofore
      unrecognized manifestations of this syndrome, which developed in a 29-year-old
      man with a history of VP shunt placement following a traumatic brain injury at
      the age of 9 years. Magnetic resonance imaging showed typical features of chronic
      intracranial hypotension, and lumbar puncture yielded an unrecordable
      subarachnoid opening pressure. The calvaria was twice its normal thickness, owing
      to contraction of the inner table. The paranasal sinuses were expanded, with
      aeration of the anterior clinoid processes, greater sphenoid wings, and temporal
      bones. The sella turcica showed a 50% reduction in cross-sectional area as
      compared with that in control subjects, resulting in partial extrusion of the
      pituitary gland. These new features broaden the spectrum of clinical findings
      associated with low ICP. Secondary installation of a valve to restore normal ICP
      is recommended to halt progression of these rare complications of VP shunt
      placement.

PMID- 23540525
TI  - Subacute cystic expansion of intracranial juvenile psammomatoid ossifying
      fibroma.
AB  - Juvenile psammomatoid ossifying fibroma (JPOF) is a benign fibro-osseous lesion
      typically associated with the jaw, paranasal region, or orbit. However, JPOF may
      also originate from the skull base and locally invade the cranium. In published
      reports, intracranial JPOFs constitute only a small percentage of cases, and
      therefore it is not known whether more aggressive behavior typifies this distinct
      population of JPOFs compared with those in other locations. Nevertheless, JPOF
      histopathology is characterized by a number of active processes, including cystic
      transformation, that may precipitate violation of skull base boundaries. In the
      following article, the authors present a case of skull base JPOF that underwent
      cystic expansion in a young girl, produced a focal neurological deficit, and was
      resolved using a staged surgical approach.

PMID- 23540526
TI  - Role of magnetic resonance ventriculography in multiloculated hydrocephalus.
AB  - OBJECT: In this paper the authors' goal was to investigate the clinical
      usefulness of Gd-enhanced MR ventriculography (MRV) in pediatric patients
      affected by multiloculated hydrocephalus. METHODS: Eighteen patients (11 boys and
      7 girls, age range 2-14 months) with a diagnosis of multiloculated hydrocephalus
      were included in the study. After injection of gadodiamide (0.02-0.04 mmol) into
      the lateral ventricle by tapping the anterior fontanel, sagittal, coronal, and
      axial T1-weighted MR images were acquired. The location of the septations and the
      sites of obstruction of CSF flow were assessed. Postoperative MRV was obtained to
      confirm the results of endoscopic treatment in most complex cases. RESULTS: No
      adverse events were observed after injection of contrast medium into the
      ventricular system. Preoperative MRV accurately defined the exact morphology of
      septae and ventricular walls in all cases. In 1 case the diagnosis of
      multiloculated hydrocephalus was ruled out. Sites of obstruction of CSF flow
      within the ventricular system were also well established. In 4 cases the multiple
      compartments were proven to intercommunicate. Postoperative MRV was useful in
      assessing the functional status of third ventriculostomy, aqueductoplasty, and
      other endoscopic fenestrations. CONCLUSIONS: Magnetic resonance ventriculography
      is a safe, effective, and reliable technique. The accurate definition of the
      anatomy of the ventricles and the site of obstruction in multiloculated
      hydrocephalus can help to plan the most appropriate treatment and minimize the
      number of procedures. Although MRV is also useful during postoperative follow-up
      to determine the results of endoscopic treatment, it should be limited to
      particularly complex cases, due to its invasiveness.

PMID- 23540527
TI  - Durable response of intracranial cellular hemangioma to bevacizumab and
      temozolomide.
AB  - Cellular hemangioma is a subtype of hemangioma that is associated with cellular
      immaturity and the potential for recurrence. Intracranial location of these
      lesions is extremely rare, and definitive treatment often requires radical
      neurosurgical resection. The authors report a case of a 12-year-old boy with a
      subtemporal cellular hemangioma. He underwent gross-total resection of the tumor,
      but within 1.5 months the tumor recurred, necessitating a second resection.
      Because of its proximity to vascular structures, only subtotal resection was
      possible. Repeat MRI 1 month after the second surgery showed significant tumor
      recurrence. Given the tumor's demonstrated capacity for recurrence and its
      proximity to the vein of Labbe and sigmoid sinus, further resection was not
      indicated. In an effort to limit radiation therapy for this young patient,
      treatment with bevacizumab and temozolomide was chosen and achieved a complete
      response that has proven durable for 36 months after cessation of therapy. This
      is the first report of the successful use of chemotherapy to treat an
      intracranial hemangioma, a rare condition with limited therapeutic options.

PMID- 23540528
TI  - A systematic review of treatment outcomes in pediatric patients with intracranial
      ependymomas.
AB  - OBJECT: Ependymoma is the third most common primary brain tumor in children.
      Tumors are classified according to the WHO pathological grading system. Prior
      studies have shown high levels of variability in patient outcomes within and
      across pathological grades. The authors reviewed the results from the published
      literature on intracranial ependymomas in children to describe clinical outcomes
      as they relate to treatment modality, associated mortality, and associated
      progression-free survival (PFS). METHODS: A search of English language peer
      reviewed articles describing patients 18 years of age or younger with
      intracranial ependymomas yielded data on 182 patients. These patients had
      undergone treatment for ependymoma with 1 of 5 modalities: 1) gross-total
      resection (GTR), 2) GTR as well as external beam radiation therapy (EBRT), 3)
      subtotal resection (STR), 4) STR as well as EBRT, or 5) radiosurgery. Mortality
      and outcome data were analyzed for time to tumor progression in patients treated
      with 1 of these 5 treatment modalities. RESULTS: Of these 182 patients, 69% had
      supratentorial ependymomas and 31% presented with infratentorial lesions.
      Regardless of tumor location or pathological grade, STR was associated with the
      highest rates of mortality. In contrast, GTR was associated with the lowest rates
      of mortality, the best overall survival, and the longest PFS. Children with WHO
      Grade II ependymomas had lower mortality rates when treated more aggressively
      with GTR. However, patients with WHO Grade III tumors had slightly better
      survival outcomes after a less aggressive surgical debulking (STR+EBRT) when
      compared with GTR. CONCLUSIONS: Mortality, PFS, and overall survival vary in
      pediatric patients with intracranial ependymomas. Pathological classification,
      tumor location, and method of treatment play a role in outcomes. In this study,
      GTR was associated with the best overall and PFS rates. Patients with WHO Grade
      II tumors had better overall survival after GTR+EBRT and better PFS after GTR
      alone. Patients with WHO Grade III tumors had better overall survival after
      STR+EBRT. Patients with infratentorial tumors had improved overall survival
      compared with those with supratentorial tumors. Progression-free survival was
      best in those patients with infratentorial tumors following STR+EBRT.
      Consideration of all of these factors is important when counseling families on
      treatment options.

PMID- 23540529
TI  - Successful treatment of post-shunt craniocerebral disproportion by coupling
      gradual external cranial vault distraction with continuous intracranial pressure
      monitoring.
AB  - A subset of hydrocephalic patients in whom shunts are placed at an early age will
      develop craniocerebral disproportion (CCD), an iatrogenic mismatch between the
      fixed intracranial volume and the growing brain. The lack of a reliable,
      reproducible method to diagnose this condition, however, has hampered attempts to
      treat it appropriately. For those practitioners who acknowledge the need to
      create more intracranial space in these patients, the lack of agreed-upon
      therapeutic end points for cranial vault expansion has limited the use of such
      techniques and has sometimes led to problems of underexpansion. Here, the authors
      present a definition of CCD based primarily on the temporal correlation of
      plateau waves on intracranial pressure (ICP) monitoring and headache
      exacerbation. The authors describe a technique of exploiting continued ICP
      monitoring during progressive cranial expansion in which the goal of distraction
      is the cessation of plateau waves. Previously encountered problems of
      underexpansion may be mitigated through the simultaneous use of ICP monitors and
      gradual cranial expansion over time.

PMID- 23540531
TI  - A comparison of classical and anatomical total knee alignment methods in robotic
      total knee arthroplasty: classical and anatomical knee alignment methods in TKA.
AB  - The purpose of this study was to compare the clinical and radiological outcomes
      achieved using classical and anatomical alignment methods in primary total knee
      arthroplasty (TKA). One hundred and seventeen patients were randomly assigned to
      undergo robotic-assisted TKA using either the classical (56 patients) or the
      anatomical alignment method (61 patients). Clinical outcomes including varus and
      valgus laxities, ROM, HSS and WOMAC scores and radiological outcomes were
      evaluated after a minimum follow-up of 2 years. Varus and valgus laxity
      assessments showed no significant inter-group differences (P>0.05). Moreover, no
      significant differences were observed in ROM, HSS and WOMAC scores (P>0.05). We
      could not find any significant difference in mechanical alignment of the lower
      limb. The results of this study show that two alignment methods provide
      comparable clinical and radiological outcomes after primary TKA.

PMID- 23540530
TI  - Biomimetic antigenic nanoparticles elicit controlled protective immune response
      to influenza.
AB  - Here we present a biomimetic strategy toward nanoparticle design for controlled
      immune response through encapsulation of conserved internal influenza proteins on
      the interior of virus-like particles (VLPs) to direct CD8+ cytotoxic T cell
      protection. Programmed encapsulation and sequestration of the conserved
      nucleoprotein (NP) from influenza on the interior of a VLP, derived from the
      bacteriophage P22, results in a vaccine that provides multistrain protection
      against 100 times lethal doses of influenza in an NP specific CD8+ T cell
      dependent manner. VLP assembly and encapsulation of the immunogenic NP cargo
      protein is the result of a genetically programmed self-assembly making this
      strategy amendable to the quick production of vaccines to rapidly emerging
      pathogens. Addition of adjuvants or targeting molecules were not required for
      eliciting the protective response.

PMID- 23540532
TI  - Can squeaking with ceramic-on-ceramic hip articulations in total hip arthroplasty
      be avoided?
AB  - Squeaking is a recognized complication of total hip arthroplasty with ceramic on
      ceramic bearings but the etiology has not been well identified. We evaluated 183
      hips in 148 patients who had undergone ceramic-on-ceramic noncemented total hip
      arthroplasties at one center between 1997-2007 by standardized telephone
      interviews and radiographic review. Audible squeaking was reported from 22 hips
      (12% of 183) of 19 patients. Prevalence of squeaking was associated with younger
      age; obesity; lateralized cup position; use of beta titanium alloy femoral
      components and shortened head length options; and higher reported activity level,
      greater pain, and decreased satisfaction at the time of the interview. Squeaking
      was described as having little personal significance by most patients. Squeaking
      might be preventable in part through medialization of the acetabular cup and
      avoidance of the use of shortened femoral necks.

PMID- 23540533
TI  - A simple method using a PACS to minimize leg length discrepancy in primary THA: a
      method to minimize leg length discrepancy.
AB  - We determined whether a PACS-based method (head-lesser trochanter distance [HLD])
      better equalized leg length discrepancy (LLD) after primary THA than a
      conventional method. We retrospectively reviewed 312 patients (379 hips) with
      osteonecrosis or primary osteoarthritis who underwent primary cementless THA: 198
      patients (240 hips) underwent THA using the HLD method, while the conventional
      group consisted of 114 patients (139 hips) in whom we measured with the method of
      McGee and Scott. We then compared the LLDs in the two groups. We observed no
      difference in the mean postoperative LLD. A higher percentage of patients in the
      HLD group had an LLD less than 6 mm: 81% vs 68% hips, respectively. HLD method
      decreases the possibility of an LLD over 6mm after THA.

PMID- 23540534
TI  - Femoral rotation in ligament balanced knee arthroplasty: a prospective clinical
      study.
AB  - Rotational alignment of the femoral component is an important factor to achieve
      beneficial results in total knee arthroplasty. Femoral rotation pre versus post
      surgery was prospectively assessed in 40 patients who underwent ligament balanced
      knee arthroplasty. Computerized tomography of the knee was performed before and
      after the surgery to determine the femoral rotation. In 36 out of 40 patients the
      rotation of the femoral implants differed compared to the preoperative femur (P >
      0.001). After surgery the rotational alignment of the femoral component ranged
      from -3 degrees  (internal rotation) to 7 degrees  (external rotation). Increased
      external rotation was found in 33 out of 40 patients ranging from 1 degrees  to 7
      degrees . These results highlight the importance of individually determined
      femoral rotation in ligament balanced knee arthroplasty.

PMID- 23540535
TI  - Apixaban and rivaroxaban decrease deep venous thrombosis but not other
      complications after total hip and total knee arthroplasty.
AB  - Apixaban and rivaroxaban are oral direct factor Xa (FXa) inhibitors used for VTE
      prevention after total hip (THA) and total knee arthroplasty (TKA). A meta
      analysis of level I studies comparing rivaroxaban 10 mg daily or apixaban 2.5 mg
      twice daily to enoxaparin for the prevention of VTE after THA or TKA was
      performed analyzing efficacy and safety outcomes. Seven studies met the inclusion
      criteria including 24,385 patients. Oral FXa inhibitors were superior to
      enoxaparin in preventing DVT (p<0.00001). There was no difference in the rate of
      PE, death, major bleeding, blood transfusion requirement, reoperation for
      bleeding or postoperative wound infections. Oral FXa inhibitors are superior to
      enoxaparin in preventing DVT after THA and TKA. There is no difference in the
      rate of PE, death, or postoperative wound complications.

PMID- 23540536
TI  - A safe zone for acetabular component position in metal-on-metal hip resurfacing
      arthroplasty: winner of the 2012 HAP PAUL award.
AB  - A safe zone for acetabular component positioning in hip resurfacing (RAIL:
      Relative Acetabular Inclination Limit) was calculated based on implant size and
      acetabular inclination angle (AIA). For AIA below the RAIL, there were no adverse
      wear failures or dislocations, and only 1% of cases with ion levels above 10
      MUg/L. Other than high inclination angle and small bearing size, female gender
      was the only other factor that correlated with high ion levels in the
      multivariate analysis. Seven hundred sixty-one hip resurfacing cases are included
      in this study. The UCLA activity score, femoral shaft angle, body mass index,
      weight, American Society of Anesthesiologists score, combined range of motion,
      diagnosis, age, gender, implant brand, AIA, bearing size, and duration of
      implantation were analyzed to determine the potential risk factors for elevated
      metal ion levels. These findings apply to sub hemispheric metal-on-metal bearings
      with similar coverage arcs as the Biomet and Corin hip resurfacing brands.
      Additional problems may occur when these bearings are connected with trunions on
      stems for total hip arthroplasty. 

PMID- 23540537
TI  - Follow-up results of 10-12 years after total hip arthroplasty using cementless
      tapered stem -- frequency of severe stress shielding with synergy stem in
      Japanese patients.
AB  - Synergy stems are tapered stems featuring a proximal porous coating, grid
      blasting below the proximal third to the distal end. This study included 41
      patients (50 hips) who underwent total hip arthroplasty with follow-ups for 10
      years or more. No stem reimplantations were performed. Spot welds were observed
      in the distal stem in Gruen zones 3 and 5 in 35 and 32 hips, respectively. First
      degree stress shielding occurred in 8 hips; 2nd-degree, 20 hips; 3rd-degree, 13
      hips; and 4th-degree, 9 hips. Because of bone fixation to the distal grit-blasted
      section of the stem, severe stress shielding was observed in nearly half of the
      cases. Multiple regression analysis of stress shielding determinants revealed a
      correlation between stem size and short patient height, showing the cause of
      stress shielding to be a mismatch in size between the stem and the femoral bone.

PMID- 23540538
TI  - The boiled-egg technique: a new method for obtaining femoral head autograft used
      in acetabular defect reconstruction.
AB  - Primary total hip arthroplasty can be complicated by acetabular bony defects,
      threatening the biomechanical integrity of the prosthesis. Traditionally, when
      autologous bone is used to pack these defects, it is obtained from thin slices of
      femoral head in addition to acetabular reamings. We report a novel technique for
      the acquisition of autologous femoral head bone graft used in the reconstruction
      of acetabular defects during primary total hip arthroplasty. 

PMID- 23540539
TI  - Economic evaluation of chlorhexidine cloths on healthcare costs due to surgical
      site infections following total knee arthroplasty.
AB  - The purpose of this study was to evaluate the overall annual healthcare cost
      savings of adding a pre-operative chlorhexidine cloth preparation protocol. We
      used reports from the National Healthcare Safety Network and previously published
      reports to determine a range of surgical site infection rates following total
      knee arthroplasty and the cost per revision procedure. The savings listed are
      potential, but may be less. The cost benefit of using chlorhexidine at our
      institution per 1,000 total knee arthroplasty patients was a net savings of
      approximately $2.1 million. The annual healthcare savings ranged from $0.78 to
      $3.18 billion. This epidemiologic evaluation of using chlorhexidine prior to
      undergoing total knee arthroplasty has demonstrated the potential to decrease
      healthcare costs primarily by decreasing the incidence of surgical site
      infections. 

PMID- 23540540
TI  - Overcoming boundaries of worldwide joint arthroplasty registers: the European
      Arthroplasty Register minimal dataset.
AB  - Worldwide joint arthroplasty registers are instrumental to screen for
      complications or implant failures. In order to achieve comparable results a
      similar classification dataset is essential. The authors therefore present the
      European Federation of National Associations of Orthopaedics and Traumatology
      (EFORT) European Arthroplasty Register (EAR) minimal dataset for primary and
      revision joint arthroplasty. Main parameters include the following: date of
      operation, country, hospital ID-code, patient's name and prename, birthday,
      identification code of the implant, gender, diagnosis, preoperations, type of
      prosthesis (partial, total), side, cementation technique, use of antibiotics in
      the cement, surgical approach, and others specifically related to the affected
      joint. The authors believe that using this minimal dataset will improve the
      chance for a worldwide comparison of arthroplasty registers and ask future
      countries for implementation. 

PMID- 23540541
TI  - Primary versus secondary distal femoral arthroplasty for treatment of total knee
      arthroplasty periprosthetic femur fractures.
AB  - Current methods of fixing periprosthetic fractures after total knee arthroplasty
      (TKA) are variable, and include open reduction and internal fixation (ORIF) via
      plating, retrograde nailing, or revision using standard revision TKA components
      or a distal femoral arthroplasty (DFA). The purpose of this study is to compare
      patients who failed plating techniques requiring subsequent revision to DFA to
      patients who underwent primary DFA. Of the 13 patients (9.2%) who failed primary
      ORIF, causes included nonunion (53.8%), infection (30.8%), loosening (7.7%), and
      refracture (7.7%). There were significantly more surgical procedures for ORIF
      revision to DFA compared to primary DFA. Complications for patients who underwent
      primary reconstruction with DFAs included extensor mechanism disruption (8.3%),
      infection (5.6%), and dislocation (2.8%). Primary reconstruction via ORIF is
      beneficial for preserving bone stock, but primary DFA may be preferred in
      osteopenic patients, or those at high risk for nonunion. 

PMID- 23540542
TI  - Dedicated orthopedic operating room unit improves operating room efficiency.
AB  - We investigated the effectiveness of dedicated orthopedic operating rooms (OR) on
      minimizing time spent on perioperative processes to increase OR throughput in
      total knee and hip arthroplasty procedures. The use of a dedicated orthopedic
      unit that included 6 ORs with staff allocated only for those ORs was compared to
      the use of a traditional staffing model. After matching to simulate
      randomization, each group consisted of 422 procedures. The dedicated orthopedic
      unit improved average anesthesia controlled time by 4 minutes (P<.001), operative
      time by 7 minutes (P=.004) and turnover time by 8 minutes (P<.001). An overall
      improvement of 19 minutes per procedure using the dedicated unit was observed.
      Utilizing a dedicated orthopedic unit can save time without increasing adverse
      events.

PMID- 23540543
TI  - Relation of distribution of coronary blood flow volume to coronary artery
      dominance.
AB  - Coronary artery dominance influences the amount and anatomic location of
      myocardium that is perfused by the left or right coronary circulation. However,
      it is unknown whether coronary artery dominance also influences the distribution
      of coronary blood flow volume. The aim of this study was to evaluate volumetric
      coronary blood flow in 1,322 vessels from 496 patients in the Prediction of
      Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular
      Profiling of Endothelial Shear Stress and Arterial Wall Morphology (PREDICTION)
      study. Patients were divided into 2 groups (right-dominant and left-dominant or
      balanced circulation). Coronary blood flow volume was calculated by coronary
      segment volume measurement using angiography and intravascular ultrasound and the
      contrast transit time through the segment. Coronary blood flow in the left
      circumflex coronary artery was significantly higher in left-dominant or balanced
      circulation than in right-dominant circulation (113 +/- 43 vs 72 +/- 37 ml/min, p
      <0.001), whereas flow in the right coronary artery was significantly lower in
      left-dominant or balanced circulation than in right-dominant circulation (56 +/-
      40 vs 113 +/- 49 ml/min, p = 0.003). There was no significant difference in the
      left anterior descending coronary artery. In conclusion, coronary artery
      dominance has an impact on coronary blood flow volume in the left circumflex and
      right coronary arteries but not in the left anterior descending coronary artery.
      These findings suggest that the extent of myocardial perfusion area is associated
      with coronary blood flow volume.

PMID- 23540544
TI  - Dramatically different phenotypic expressions of hypertrophic cardiomyopathy in
      male cousins undergoing cardiac transplantation with identical disease-causing
      gene mutation.
AB  - Described herein are certain findings in 2 male cousins who underwent cardiac
      transplantation for severe heart failure (HF), one of the diastolic type
      (ejection fraction ~65%), and one of the systolic type (ejection fraction ~20%),
      both the consequence of hypertrophic cardiomyopathy (HC), and each had identical
      disease-causing gene mutations. The implanted heart in one had normal-sized
      ventricular cavities and no grossly visible ventricular wall lesions (except in
      one papillary muscle) and the other patient had severely dilated ventricular
      cavities and multiple extensive ventricular wall scars. The heart mass and the
      age of onset of symptoms was similar in each patient. A number of other family
      members had evidence of HC.

PMID- 23540545
TI  - Comparison of rate versus rhythm control in patients with atrial fibrillation and
      a pacemaker.
AB  - The effect of rate versus rhythm control in patients with atrial fibrillation who
      have undergone previous pacemaker (PM) implantation is unknown. We evaluated the
      mortality in patients with atrial fibrillation and a PM randomized to rate or
      rhythm control treatment strategies. The Atrial Fibrillation Follow-up
      Investigation of Rhythm Management data set was stratified by the presence (n =
      250) or absence (n = 3,810) of a PM at randomization into the rate or rhythm
      control arm. Kaplan-Meier curves were used for univariate analysis, and
      proportional hazards were used for multivariate analysis. The subjects with a PM
      (n = 250) were older (73 vs 69 years, p <0.01) and had a greater prevalence of
      coronary artery disease (53% vs 37%, p <0.01) and congestive heart failure (33%
      vs 23%, p <0.01). All-cause mortality was significantly greater in the PM
      patients who were randomized to the rhythm control arm (n = 128) than in the
      patients enrolled in the rate control arm with or without a PM (n = 2,027, p
      <0.01) and those in the rhythm control arm without a PM (n = 1,905, p <0.01).
      Multivariate analysis revealed that predictors of all-cause mortality included PM
      patients randomized to the rhythm control arm (hazard ratio 2.59, 95% confidence
      interval 1.46 to 4.58, p <0.01) and the presence of congestive heart failure
      (hazard ratio 2.42, 95% confidence interval 1.40 to 4.16, p <0.01). In
      conclusion, all-cause mortality was greater among patients with atrial
      fibrillation with a PM, who were randomized to the rhythm control arm of the
      Atrial Fibrillation Follow-up Investigation of Rhythm Management study compared
      with all other patients enrolled in the Atrial Fibrillation Follow-up
      Investigation of Rhythm Management study. The rhythm control strategy in patients
      with a PM was an independent predictor of mortality.

PMID- 23540546
TI  - Causes of death in patients >=75 years of age with non-ST-segment elevation acute
      coronary syndrome.
AB  - The causes of death within 1 year of hospital admission in patients with non-ST
      segment elevation acute coronary syndromes are ill defined, particularly in
      patients aged >=75 years. From January 2008 through May 2010, we enrolled 645
      patients aged >=75 years with non-ST-segment elevation acute coronary syndromes:
      313 in a randomized trial comparing an early aggressive versus an initially
      conservative approach, and 332, excluded from the trial for specific reasons, in
      a parallel registry. Each death occurring during 1 year of follow-up was
      adjudicated by an independent committee. The mean age was 82 years in both study
      cohorts, and 53% were men. By the end of the follow-up period (median 369 days,
      interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was
      significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths
      were classified as cardiac in 94% of the cases during the index admission and 68%
      of the cases during the follow-up period. Eighty-six percent of the cardiac
      deaths were of ischemic origin. In a multivariate logistic regression model that
      included the variables present on admission in the whole study population, the
      ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p
      <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to
      0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to
      1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence
      interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause
      death at 1 year. In conclusion, within 1 year after admission for non-ST-segment
      elevation acute coronary syndromes, most deaths in patients aged >=75 years have
      a cardiac origin, mostly owing to myocardial ischemia.

PMID- 23540547
TI  - Association of cardiac troponin I with disease severity and outcomes in patients
      with pulmonary hypertension.
AB  - Previous studies have identified cardiac troponin I (cTnI) as an important marker
      in pulmonary hypertension (PH) prognosis. However, traditional assays are limited
      by poor sensitivity, even among patients at high risk. cTnI was measured in 255
      PH patients using a new highly sensitive (hs) assay. Other measures included
      demographics, creatinine, 6-minute walk distance, hemodynamics, cardiac magnetic
      resonance imaging, and B-type natriuretic peptide level. The association between
      cTnI and survival was assessed using Kaplan-Meier analysis and Cox regression.
      cTnI was detectable with the hs assay in 95% of the patients with a median level
      of 6.9 pg/ml (IQR 2.7-12.6 pg/ml). Higher cTnI levels associated with higher
      levels of B-type natriuretic peptide, shorter 6-minute walk distance, and more
      severe hemodynamic and cardiac magnetic resonance imaging abnormalities. During a
      median follow-up of 3.5 years, 60 individuals died. Unadjusted event rates
      increased across higher cTnI quartiles (3, 5, 13, 17 events/100 person-years,
      respectively, p trend = 0.002). cTnI in the fourth (vs first) quartile remained
      associated with death in a final stepwise multivariable model that included
      clinical variables and hemodynamics (adjusted hazard ratio 5.3, 95% confidence
      interval 1.8-15.6). In conclusion, cTnI levels, detectable with a novel hs assay,
      identify patients with PH who have more severe hemodynamic and cardiac structural
      abnormalities and provide novel and independent prognostic information. This hs
      assay has the potential to detect more at-risk patients and improve current risk
      stratification algorithms.

PMID- 23540548
TI  - Risk of death in long-term follow-up of patients with apical hypertrophic
      cardiomyopathy.
AB  - Apical hypertrophic cardiomyopathy (HC) has been considered a "benign" form of
      HC, with limited data on long-term outcome. We compared apical HC patients with a
      non-HC, age- and gender-matched Minnesota white population to identify outcomes
      and prognostic factors. Between 1976 and 2006, 193 patients (62% men) with apical
      HC were seen at our clinic. Their most recent echocardiographic examinations were
      reviewed. Mean +/- SD age at first presentation was 58 +/- 17 years. A family
      history of HC or sudden cardiac death (SCD) was reported by 43 patients (22%);
      coronary artery disease was known in 22 (11%). An apical pouch was present in 29
      patients, including an apical aneurysm in 6 and apical dilatation with
      hypokinesis in 23. Median follow-up (187 patients [97%]) was 78 months (range, 1
      350). Death from all causes occurred in 55 patients (29%; 33 women) at a mean age
      of 72 years (range, 20-92). During follow-up, more women had heart failure (p =
      0.001), atrial fibrillation (p = 0.009), or died (p <0.001) than men. Survival
      was worse than expected (p = 0.001); the observed versus expected 20-year
      survival was 47% versus 60%. SCD, resuscitated cardiac arrest, and/or
      defibrillator discharge was observed in 11 patients (6%) during follow-up.
      Multivariate predictors of decreased survival were higher age at baseline (p
      <0.001), female gender (p <0.001), and atrial fibrillation at baseline (p =
      0.06). In conclusion, apical HC in this population was associated with increased
      mortality, especially in women. Because apical HC is less benign than previously
      suspected, careful longitudinal care is warranted.

PMID- 23540549
TI  - Invasive assessment of doubtful aortic stenosis by measuring simultaneous
      transaortic gradient with a pressure wire.
AB  - Two-dimensional transthoracic echocardiography (2D-TTE) is the reference
      technique for evaluating aortic stenosis (AS) but may be unreliable in some
      cases. We aimed to assess whether the use of a pressure wire to measure
      simultaneous transaortic gradient and aortic valve area (AVA) could be helpful in
      patients in whom initial noninvasive evaluations were considered doubtful for AS.
      Fifty-seven patients (mean age 76 years; 39 men) underwent cardiac
      catheterization with single arterial access for assessment of AVA with the Gorlin
      and Gorlin formula. Transaortic pressure was obtained by 2 invasive methods: (1)
      conventional pullback method (PM) from the left ventricle toward the aorta and
      (2) simultaneous method (SM) with transaortic pressure simultaneously recorded
      with a 0.014-inch pressure wire introduced into the left ventricle and with a
      diagnostic catheter placed in the ascending aorta. Reasons for inaccurate
      assessment by 2D-TTE were low flow states (88%) and/or atrial fibrillation (79%).
      Agreement for severe AS defined by AVA <0.6 cm2/m2 between SM and 2D-TTE and
      between SM and PM was fair, with kappa coefficients of 0.38 (95% confidence
      interval [CI] 0.14-0.75) and 0.36 (95% CI 0.22-0.7) respectively; agreement was
      poor between 2D-TTE and PM (kappa: 0.23; 95% CI 0.002-0.36). SM led to a
      reclassification of the severity of AS in 9 patients (15.8%) compared with 2D-TTE
      and in 11 patients (19.3%) compared with PM. In conclusion, invasive evaluation
      of doubtful AS by measuring simultaneous transaortic gradient using a pressure
      wire may provide an attractive method that can lead to a change in therapeutic
      strategy in a substantial proportion of patients.

PMID- 23540551
TI  - Dysphagia and trismus after concomitant chemo-Intensity-Modulated Radiation
      Therapy (chemo-IMRT) in advanced head and neck cancer; dose-effect relationships
      for swallowing and mastication structures.
AB  - BACKGROUND AND PURPOSE: Prospective assessment of dysphagia and trismus in chemo
      IMRT head and neck cancer patients in relation to dose-parameters of structures
      involved in swallowing and mastication. MATERIAL AND METHODS: Assessment of 55
      patients before, 10-weeks (N=49) and 1-year post-treatment (N=37). Calculation of
      dose-volume parameters for swallowing (inferior (IC), middle (MC), and superior
      constrictors (SC)), and mastication structures (e.g. masseter). Investigation of
      relationships between dose-parameters and endpoints for swallowing problems
      (videofluoroscopy-based laryngeal Penetration-Aspiration Scale (PAS), and study
      specific structured questionnaire) and limited mouth-opening (measurements and
      questionnaire), taking into account baseline scores. RESULTS: At 10-weeks, volume
      of IC receiving >=60 Gy (V60) and mean dose IC were significant predictors for
      PAS. One-year post-treatment, reported problems with swallowing solids were
      significantly related to masseter dose-parameters (mean, V20, V40 and V60) and an
      inverse relationship (lower dose related to a higher probability) was observed
      for V60 of the IC. Dose-parameters of masseter and pterygoid muscles were
      significant predictors of trismus at 10-weeks (mean, V20, and V40). At 1-year,
      dose-parameters of all mastication structures were strong predictors for
      subjective mouth-opening problems (mean, max, V20, V40, and V60). CONCLUSIONS:
      Dose-effect relationships exist for dysphagia and trismus. Therefore treatment
      plans should be optimized to avoid these side effects.

PMID- 23540552
TI  - Comment on: "Increased treatment-related mortality with additional cisplatin
      based chemotherapy in patients with nasopharyngeal carcinoma treated with
      standard radiotherapy".

PMID- 23540550
TI  - Glycocapture-assisted global quantitative proteomics (gagQP) reveals multiorgan
      responses in serum toxicoproteome.
AB  - Blood is an ideal window for viewing our health and disease status. Because blood
      circulates throughout the entire body and carries secreted, shed, and excreted
      signature proteins from every organ and tissue type, it is thus possible to use
      the blood proteome to achieve a comprehensive assessment of multiple-organ
      physiology and pathology. To date, the blood proteome has been frequently
      examined for diseases of individual organs; studies on compound insults impacting
      multiple organs are, however, elusive. We believe that a characterization of
      peripheral blood for organ-specific proteins affords a powerful strategy to allow
      early detection, staging, and monitoring of diseases and their treatments at a
      whole-body level. In this paper we test this hypothesis by examining a mouse
      model of acetaminophen (APAP)-induced hepatic and extra-hepatic toxicity. We used
      a glycocapture-assisted global quantitative proteomics (gagQP) approach to study
      serum proteins and validated our results using Western blot. We discovered in
      mouse sera both hepatic and extra-hepatic organ-specific proteins. From our
      validation, it was determined that selected organ-specific proteins had changed
      their blood concentration during the course of toxicity development and recovery.
      Interestingly, the peak responding time of proteins specific to different organs
      varied in a time-course study. The collected molecular information shed light on
      a complex, dynamic, yet interweaving, multiorgan-enrolled APAP toxicity. The
      developed technique as well as the identified protein markers is translational to
      human studies. We hope our work can broaden the utility of blood proteomics in
      diagnosis and research of the whole-body response to pathogenic cues.

PMID- 23540553
TI  - The effect of concomitant chemotherapy on parotid gland function following head
      and neck IMRT.
AB  - PURPOSE: To determine whether concomitant chemotherapy increases the incidence of
      high grade xerostomia following parotid-sparing intensity-modulated radiotherapy
      (IMRT) in patients with locally advanced head and neck squamous cell cancer.
      MATERIALS AND METHODS: The incidence of high grade (>=G2) acute (CTCAEv3.0) and
      late (LENTSOMA and RTOG) xerostomia was compared between patients treated with
      either IMRT or concomitant chemo-IMRT (c-IMRT) in 2 prospective studies. Parotid
      gland mean tolerance doses (D50) were reported using non-linear logistic
      regression analysis. RESULTS: Thirty-six patients received IMRT alone and 60
      patients received c-IMRT. Patients received 65 Gy in 30 daily fractions to the
      primary site and involved nodal groups and 54 Gy in 30 fractions to elective
      nodal groups, mean doses to the parotid glands were comparable. Concomitant
      cisplatin 100mg/m(2) was administered on days 1 and 29 of IMRT. The incidence of
      >=G2 subjective xerostomia was similar in both groups; acute-64.7% (IMRT) versus
      60.3% (c-IMRT), p=0.83; late-43% (IMRT) versus 34% (c-IMRT), p=0.51. Recovery of
      parotid salivary flow at 1 year was higher with IMRT (64% vs 50%), but not
      statistically significant (p=0.15). D50 for absence of parotid saliva flow at 1
      year was 23.2 Gy (95% CI: 17.7-28.7) for IMRT and 21.1 Gy (11.8-30.3) for c-IMRT.
      CONCLUSION: Concomitant c-IMRT does not increase the incidence of acute or late
      xerostomia relative to IMRT alone.

PMID- 23540554
TI  - Comparison of X-ray and alpha particle effects on a human cancer and endothelial
      cells: survival curves and gene expression profiles.
AB  - BACKGROUND AND PURPOSE: Tumours are now considered as complex tissues including
      endothelial cells of the tumour vasculature, which can decrease radiotherapy
      efficacy. It is thus important to better characterise the response of both types
      of cells to irradiation. This study investigated the effects of X-ray and alpha
      particle irradiation on cancer and endothelial cells. MATERIALS AND METHODS: A549
      non-small-cell lung adenocarcinoma cells and human endothelial cells (EC) were
      exposed to X-rays or alpha particles. Responses were studied by clonogenic assays
      and nuclei staining. A gene expression study was performed by using Taqman low
      density array and the results were validated by qRT-PCR and ELISA. RESULTS: The
      relative biological effectiveness of alpha particles was estimated to be 5.5 and
      4.6 for 10% survival of A549 cells and EC, respectively. Nuclei staining
      indicated that mitotic catastrophe was the main type of cell death induced by X
      rays and alpha particles. Both ionising radiations induced the overexpression of
      genes involved in cell growth, inflammation and angiogenesis. CONCLUSIONS: Alpha
      particle irradiations are more effective than X-rays. The gene expression changes
      observed in both cell types after alpha particle or X-ray exposure showed
      possible crosstalk between both cell types that may induce the development of
      radioresistance.

PMID- 23540555
TI  - Tumor and normal tissue dosimetry changes during MR-guided pulsed-dose-rate (PDR)
      brachytherapy for cervical cancer.
AB  - BACKGROUND AND PURPOSE: To analyze systematic changes in tumor and normal tissue
      anatomy and dosimetry using serial MR imaging during pulsed dose rate
      brachytherapy (PDR BT) for cervical cancer. MATERIAL AND METHODS: Forty-three
      patients with cervical cancer underwent MR-guided PDR BT using an intrauterine
      applicator alone after external beam radiotherapy. MR imaging was repeated on
      days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured
      volumes. RESULTS: The mean uterine volume and mean HR CTV increased during
      treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day
      1 planned dose. There was no change in the mean bladder volume during treatment
      but the mean rectal volume increased. This correlated with an increase in the
      mean rectal dose. There were four local recurrences. There was no apparent
      relationship between either the planned or the delivered HR CTV D90 and local
      recurrence. There was only one case of late bladder toxicity but nine patients
      developed late rectal toxicity. The cumulative rectal dose during treatment was a
      better predictor of late rectal toxicity than the planned dose. CONCLUSIONS:
      Significant changes in tumor and normal tissue anatomy and dosimetry can occur
      during PDR BT and should be tracked and corrected using serial imaging and plan
      adaptation, especially when the day 1 tumor or normal tissue doses are close to
      the planning constraints.

PMID- 23540556
TI  - Trends and applications of fast liquid chromatography in bioanalysis. (preface).

PMID- 23540557
TI  - A comparison of DNA compaction by arginine and lysine peptides: a physical basis
      for arginine rich protamines.
AB  - Protamines are small, highly positively charged peptides used to package DNA at
      very high densities in sperm nuclei. Tight DNA packing is considered essential
      for the minimization of DNA damage by mutagens and reactive oxidizing species. A
      striking and general feature of protamines is the almost exclusive use of
      arginine over lysine for the positive charge to neutralize DNA. We have
      investigated whether this preference for arginine might arise from a difference
      in DNA condensation by arginine and lysine peptides. The forces underlying DNA
      compaction by arginine, lysine, and ornithine peptides are measured using the
      osmotic stress technique coupled with X-ray scattering. The equilibrium spacings
      between DNA helices condensed by lysine and ornithine peptides are significantly
      larger than the interhelical distances with comparable arginine peptides. The DNA
      surface-to-surface separation, for example, is some 50% larger with polylysine
      than with polyarginine. DNA packing by lysine rich peptides in sperm nuclei would
      allow much greater accessibility to small molecules that could damage DNA. The
      larger spacing with lysine peptides is caused by both a weaker attraction and a
      stronger short-range repulsion relative to that of the arginine peptides. A
      previously proposed model for binding of polyarginine and protamine to DNA
      provides a convenient framework for understanding the differences between the
      ability of lysine and arginine peptides to assemble DNA.

PMID- 23540559
TI  - The reliability of clinical dynamic monitoring of redox status using a new redox
      potential (ORP) determination method.
AB  - PURPOSE: Quantitative monitoring of the redox status is the foundation for redox
      related treatment. The purpose of this study was to evaluate the reliability of a
      new depolarization curve method for plasma redox potential (ORP) monitoring.
      METHODS: Using the new method, we performed redox determinations for the first
      time under different sample-handling conditions, including redox titration
      experiments using KMnO4 and vitamin C and dynamic redox monitoring in burn
      patients. The relative ORP value (DeltaORP) method (improved traditional method)
      was used as the reference. RESULTS: The new method's better reliability,
      electrochemical specificity and practicability, and known group validity, which
      are closely associated with the redox-related pathological processes of severe
      burns, were confirmed. Furthermore, bidirectional change in the redox status in
      severe burn patients was also observed for the first time. CONCLUSIONS: This
      simple, stable new method could be a better practical tool for making the dynamic
      monitoring of the redox status feasible and for providing useful quantitative
      information for the judgment of redox-related pathological process, thus
      improving corresponding individualized treatments that rely on quantitative
      adjustments to the redox status.

PMID- 23540560
TI  - Arm lymphoedema after breast cancer.

PMID- 23540561
TI  - Incidence of unilateral arm lymphoedema after breast cancer: a systematic review
      and meta-analysis.
AB  - BACKGROUND: The body of evidence related to breast-cancer-related lymphoedema
      incidence and risk factors has substantially grown and improved in quality over
      the past decade. We assessed the incidence of unilateral arm lymphoedema after
      breast cancer and explored the evidence available for lymphoedema risk factors.
      METHODS: We searched Academic Search Elite, Cumulative Index to Nursing and
      Allied Health, Cochrane Central Register of Controlled Trials (clinical trials),
      and Medline for research articles that assessed the incidence or prevalence of,
      or risk factors for, arm lymphoedema after breast cancer, published between Jan
      1, 2000, and June 30, 2012. We extracted incidence data and calculated
      corresponding exact binomial 95% CIs. We used random effects models to calculate
      a pooled overall estimate of lymphoedema incidence, with subgroup analyses to
      assess the effect of different study designs, countries of study origin,
      diagnostic methods, time since diagnosis, and extent of axillary surgery. We
      assessed risk factors and collated them into four levels of evidence, depending
      on consistency of findings and quality and quantity of studies contributing to
      findings. FINDINGS: 72 studies met the inclusion criteria for the assessment of
      lymphoedema incidence, giving a pooled estimate of 16.6% (95% CI 13.6-20.2). Our
      estimate was 21.4% (14.9-29.8) when restricted to data from prospective cohort
      studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2
      years after diagnosis or surgery of breast cancer (24 studies with time since
      diagnosis or surgery of 12 to <24 months; 18.9%, 14.2-24.7), was highest when
      assessed by more than one diagnostic method (nine studies; 28.2%, 11.8-53.5), and
      was about four times higher in women who had an axillary-lymph-node dissection
      (18 studies; 19.9%, 13.5-28.2) than it was in those who had sentinel-node biopsy
      (18 studies; 5.6%, 6.1-7.9). 29 studies met the inclusion criteria for the
      assessment of risk factors. Risk factors that had a strong level of evidence were
      extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph
      nodes dissected, mastectomy) and being overweight or obese. INTERPRETATION: Our
      findings suggest that more than one in five women who survive breast cancer will
      develop arm lymphoedema. A clear need exists for improved understanding of
      contributing risk factors, as well as of prevention and management strategies to
      reduce the individual and public health burden of this disabling and distressing
      disorder. FUNDING: The National Breast Cancer Foundation, Australia.

PMID- 23540562
TI  - Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after
      imatinib resistance.
AB  - The occurrence of resistance mutations in the Abl kinase domain plays a central
      role in drug treatment failure in chronic myeloid leukemia (CML) patients. Among
      them, the T315I mutation at the gatekeeper position affects a common Abl kinase
      contact residue and confers complete resistance to all known ATP-competitive BCR
      ABL inhibitors. In the present study, an allele-specific oligonucleotide reverse
      transcriptase polymerase chain reaction assay was used to detect T315I mutation
      in a cohort of 60 imatinib-resistant CML patients. In terms of disease phase, 43
      patients (71%) were in late chronic phase, 4 (7%) in accelerated phase, and 13
      (22%) in blastic phase. The prevalence of the T315I mutation was found to be 7%
      (4/60). All four patients with mutation were in advance phases and had previously
      lost all their responses. The results of the study confirmed that this method is
      low cost and easy tool to operate for T315I mutation screening and direct
      sequencing should be performed in positive cases for confirmation.

PMID- 23540563
TI  - [Financial rating optimization in pressure ulcers management: yes, but at what
      price?].
AB  - The surgical management of pressure ulcers remains very expensive even if
      preventive measures and improved care pathways allowed to reduce spending in this
      domain in recent years. Since 2004, the funding of French hospitals by "fee-for
      service" and the needs of saving health spending necessarily compels us to
      interest ourselves in these purely economic considerations and sometimes modify
      our requirements for hospital stay to optimize a "patient' valorisation group".
      In the future, this may lead the surgeon to bias the real needs of the patient
      for the benefit of hospital establishment. Through a medico-economic analysis of
      our practices conducted in the plastic surgery department of the University
      hospital of Toulouse, we tried to identify how to optimize the surgical
      management of pressure ulcers in terms of valorisation of hospital stay. The aim
      is still to remain critical about the aberrations that this could introduce in
      the future for our clinical activity.

PMID- 23540564
TI  - Secretion and extracellular space travel of Wnt proteins.
AB  - Wnt signaling pathways control many processes during development, stem cell
      maintenance and homeostasis, and their aberrant regulation has been linked to
      diseases in man including diabetes, neurodegeneration and cancer. Wnts are
      hydrophobic proteins, however, quite paradoxically, they can travel over
      distances to induce cell-type specific responses. While there has been an initial
      focus on elucidating the intracellular signaling cascade, discoveries in the past
      few years have shed light on a highly complex, and regulated secretory process
      that guides Wnt proteins through the exocytic pathway. Wnt proteins are at least
      in portion packaged onto extracellular carriers such as exosomes. Similar to
      dysregulation of components in the Wnt receiving cell, failure to regulate Wnt
      secretion has been linked to cancer. Here, we review recent discoveries on
      factors and processes implicated in Wnt secretion. 

PMID- 23540565
TI  - [Chorda tympani neuroma].

PMID- 23540566
TI  - Diabetes mellitus and the occurrence of colorectal cancer: an updated meta
      analysis of cohort studies.
AB  - BACKGROUND: Recently, it has been found that diabetes patients have a higher
      incidence of colorectal cancer than the general population, but epidemiological
      studies examining a potential relationship between the two have produced
      inconsistent conclusions. Thus, we set out to perform a meta-analysis of cohort
      studies to evaluate the association between diabetes and colorectal cancer.
      MATERIALS AND METHODS: Using "diabetes," "colorectal cancer," and associated key
      words, we performed a systematic review of published cohort studies in multiple
      databases, including MEDLINE, EMBASE, ISI Web of Knowledge databases, OVID, CNKI,
      CBMD ISC, WANFANG, and CQVIP. We then applied stringent inclusion and exclusion
      criteria to identify which studies to include in our analysis. STATA version 12.0
      software (StataCorp., College Station, TX) was used to conduct statistical
      analysis, including consolidated statistics calculations, tests for
      heterogeneity, and publication bias evaluations. RESULTS: We obtained a total of
      532 potential articles. In accordance with our inclusion and exclusion criteria,
      we selected 29 articles for the meta-analysis. The analysis of extracted
      information indicated that diabetes is a risk factor for the development of
      colorectal cancer (relative risk 1.22, 95% confidence interval 1.19-1.26).
      Subgroup analyses by control populations, regions, gender, follow-up time, and
      colorectal cancer site also support this finding. CONCLUSIONS: The risk of
      individuals with diabetes to develop colorectal cancer is 1.22 times higher than
      that of individuals without diabetes. The positive association remains consistent
      for both men and women and for studies carried out in North America, Europe, and
      Asia, as well as for different follow-up times.

PMID- 23540567
TI  - Pd(II)-catalyzed sequential C-C/C-O bond formations: a new strategy to construct
      trisubstituted furans.
AB  - Palladium-catalyzed oxidative difunctionalization of enol ethers with 1,3
      dicarbonyl compounds to construct trisubstituted furans in one step under mild
      conditions is described. The reaction is thought to proceed through a C-C bond
      formation along with a C-O bond closing the ring structure. Oxygen is the sole
      oxidant regenerating the Pd(II) catalyst.

PMID- 23540568
TI  - Aminosilane-grafted polymer/silica hollow fiber adsorbents for CO2 capture from
      flue gas.
AB  - Amine/silica/polymer composite hollow fiber adsorbents are produced using a novel
      reactive post-spinning infusion technique, and the obtained fibers are shown to
      capture CO2 from simulated flue gas. The post-spinning infusion technique allows
      for functionalization of polymer/silica hollow fibers with different types of
      amines during the solvent exchange step after fiber spinning. The post-spinning
      infusion of 3-aminopropyltrimethoxysilane (APS) into mesoporous silica/cellulose
      acetate hollow fibers is demonstrated here, and the materials are compared with
      hollow fibers infused with poly(ethyleneimine) (PEI). This approach results in
      silica/polymer composite fibers with good amine distribution and accessibility,
      as well as adequate porosity retained within the fibers to facilitate rapid mass
      transfer and adsorption kinetics. The CO2 adsorption capacities for the APS
      infused hollow fibers are shown to be comparable to those of amine powders with
      similar amine loadings. In contrast, fibers that are spun with presynthesized,
      amine-loaded mesoporous silica powders show negligible CO2 uptake and low amine
      loadings because of loss of amines from the silica materials during the fiber
      spinning process. Aminosilica powders are shown to be more hydrophilic than the
      corresponding amine containing composite hollow fibers, the bare polymer as well
      as silica support. Both the PEI-infused and APS-infused fibers demonstrate
      reduced CO2 adsorption upon elevating the temperature from 35 to 80  degrees C,
      in accordance with thermodynamics, whereas PEI-infused powders show increased CO2
      uptake over that temperature range because of competing diffusional and
      thermodynamic effects. The CO2 adsorption kinetics as probed via TGA show that
      the APS-infused hollow fiber adsorbents have more rapid uptake kinetics than
      their aminosilica powder analogues. The adsorption performance of the
      functionalized hollow fibers is also assessed in CO2 breakthrough experiments.
      The breakthrough results show a sharp CO2 front for APS-grafted fibers,
      indicating fast kinetics with comparable pseudo-equilibrium capacities to the CO2
      equilibrium capacities measured via thermogravimetric analysis (TGA). The results
      indicate the post-spinning infusion method provides a new platform for
      synthesizing composite polymer/silica/amine fibers that may facilitate the
      ultimate scale-up of practical fiber adsorbents for flue gas CO2 capture
      applications.

PMID- 23540569
TI  - Are managed care organizations in the United States impeding the delivery of
      primary care by nurse practitioners? A 2012 update on managed care organization
      credentialing and reimbursement practices.
AB  - In 2014, the Affordable Care Act will create an estimated 16 million newly
      insured people. Coupled with an estimated shortage of over 60,000 primary care
      physicians, the country's public health care system will be at a challenging
      crossroads, as there will be more patients waiting to see fewer doctors. Nurse
      practitioners (NPs) can help to ease this crisis. NPs are health care
      professionals with the capability to provide important and critical access to
      primary care, particularly for vulnerable populations. However, despite
      convincing data about the quality of care provided by NPs, many managed care
      organizations (MCOs) across the country do not credential NPs as primary care
      providers, limiting the ability of NPs to be reimbursed by private insurers. To
      assess current credentialing practices of health plans across the United States,
      a brief telephone survey was administered to 258 of the largest health
      maintenance organizations (HMOs) in the United States, operated by 98 different
      MCOs. Results indicated that 74% of these HMOs currently credential NPs as
      primary care providers. Although this represents progress over prior assessments,
      findings suggest that just over one fourth of major HMOs still do not recognize
      NPs as primary care providers. Given the documented shortage of primary care
      physicians in low-income communities in the United States, these credentialing
      policies continue to diminish the ability of NPs to deliver primary care to
      vulnerable populations. Furthermore, these policies could negatively impact
      access to care for thousands of newly insured Americans who will be seeking a
      primary care provider in 2014.

PMID- 23540570
TI  - Ruthenium-based electrocatalysts supported on reduced graphene oxide for lithium
      air batteries.
AB  - Ruthenium-based nanomaterials supported on reduced graphene oxide (rGO) have been
      investigated as air cathodes in non-aqueous electrolyte Li-air cells using a
      TEGDME-LiCF3SO3 electrolyte. Homogeneously distributed metallic ruthenium and
      hydrated ruthenium oxide (RuO2.0.64H2O), deposited exclusively on rGO, have been
      synthesized with average size below 2.5 nm. The synthesized hybrid materials of
      Ru-based nanoparticles supported on rGO efficiently functioned as
      electrocatalysts for Li2O2 oxidation reactions, maintaining cycling stability for
      30 cycles without sign of TEGDME-LiCF3SO3 electrolyte decomposition.
      Specifically, RuO2.0.64H2O-rGO hybrids were superior to Ru-rGO hybrids in
      catalyzing the OER reaction, significantly reducing the average charge potential
      to ~3.7 V at the high current density of 500 mA g(-1) and high specific capacity
      of 5000 mAh g(-1).

PMID- 23540571
TI  - Designing trials for pressure ulcer risk assessment research: methodological
      challenges.
AB  - For decades various pressure ulcer risk assessment scales (PURAS) have been
      developed and implemented into nursing practice despite uncertainty whether use
      of these tools helps to prevent pressure ulcers. According to current
      methodological standards, randomised controlled trials (RCTs) are required to
      conclusively determine the clinical efficacy and safety of this risk assessment
      strategy. In these trials, PURAS-aided risk assessment has to be compared to
      nurses' clinical judgment alone in terms of its impact on pressure ulcer
      incidence and adverse outcomes. However, RCTs evaluating diagnostic procedures
      are prone to specific risks of bias and threats to the statistical power which
      may challenge their validity and feasibility. This discussion paper critically
      reflects on the rigour and feasibility of experimental research needed to
      substantiate the clinical efficacy of PURAS-aided risk assessment. Based on
      reflections of the methodological literature, a critical appraisal of available
      trials on this subject and an analysis of a protocol developed for a
      methodologically robust cluster-RCT, this paper arrives at the following
      conclusions: First, available trials do not provide reliable estimates of the
      impact of PURAS-aided risk assessment on pressure ulcer incidence compared to
      nurses' clinical judgement alone due to serious risks of bias and insufficient
      sample size. Second, it seems infeasible to assess this impact by means of
      rigorous experimental studies since sample size would become extremely high if
      likely threats to validity and power are properly taken into account. Third,
      means of evidence linkages seem to currently be the most promising approaches for
      evaluating the clinical efficacy and safety of PURAS-aided risk assessment. With
      this kind of secondary research, the downstream effect of use of PURAS on
      pressure ulcer incidence could be modelled by combining best available evidence
      for single parts of this pathway. However, to yield reliable modelling results,
      more robust experimental research evaluating specific parts of the pressure ulcer
      risk assessment-prevention pathway is needed.

PMID- 23540572
TI  - Corneal decompensation and angle-closure glaucoma after upside-down implantation
      of an angle-supported anterior chamber phakic intraocular lens.
AB  - We present the case of a 27-year-old man with severe pain, loss of visual acuity,
      corneal edema, and high intraocular pressure (IOP) in 1 eye after bilateral
      Acrysof Cachet phakic intraocular lens (pIOL) implantation. Slitlamp examination
      was limited due to severe corneal edema, but anterior segment optical coherence
      tomography indicated upside-down implantation of the pIOL. The pIOL was
      explanted, which confirmed that the haptic indicator had been implanted
      counterclockwise. Postoperative treatment included antiinflammatory and
      antiglaucoma topical therapy. Follow-up monitoring showed decreasing corneal
      edema and normalized IOP. At 6 weeks, the corrected distance visual acuity was
      +0.1 logMAR, the IOP was within normal limits, and the cornea showed no signs of
      edema, but there was endothelial cell density loss. This case presents the
      preoperative and postoperative management of high IOP after pIOL implantation and
      illustrates the pitfalls of incorrect implantation of angle-supported anterior
      chamber IOLs with haptic angulation.

PMID- 23540574
TI  - Human serum/plasma lipoprotein analysis by NMR: application to the study of
      diabetic dyslipidemia.

PMID- 23540576
TI  - Non-linear liquid-state NMR.

PMID- 23540573
TI  - Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1
      expression through long-range enhancers.
AB  - Analysis of 4,405 variants in 89,050 European subjects from 41 case-control
      studies identified three independent association signals for estrogen-receptor
      positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer
      element in which the G allele of the best candidate causative variant rs554219
      increases risk of breast cancer, reduces both binding of ELK4 transcription
      factor and luciferase activity in reporter assays, and may be associated with low
      cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies
      in the same enhancer element. Risk association signal 2, rs75915166, creates a
      GATA3 binding site within a silencer element. Chromatin conformation studies
      demonstrate that these enhancer and silencer elements interact with each other
      and with their likely target gene, CCND1.

PMID- 23540577
TI  - Effectiveness of physical therapy in treating atraumatic full-thickness rotator
      cuff tears: a multicenter prospective cohort study.
AB  - PURPOSE: To assess the effectiveness of a specific nonoperative physical therapy
      program in treating atraumatic full-thickness rotator cuff tears using a
      multicenter prospective cohort study design. MATERIALS AND METHODS: Patients with
      atraumatic full-thickness rotator cuff tears who consented to enroll provided
      data via questionnaire on demographics, symptom characteristics, comorbidities,
      willingness to undergo surgery, and patient-related outcome assessments (Short
      Form 12 score, American Shoulder and Elbow Surgeons score, Western Ontario
      Rotator Cuff score, Single Assessment Numeric Evaluation score, and Shoulder
      Activity Scale). Physicians recorded physical examination and imaging data.
      Patients began a physical therapy program developed from a systematic review of
      the literature and returned for evaluation at 6 and 12 weeks. At those visits,
      patients could choose 1 of 3 courses: (1) cured (no formal follow-up scheduled),
      (2) improved (continue therapy with scheduled reassessment in 6 weeks), or (3) no
      better (surgery offered). Patients were contacted by telephone at 1 and 2 years
      to determine whether they had undergone surgery since their last visit. A
      Wilcoxon signed rank test with continuity correction was used to compare initial,
      6-week, and 12-week outcome scores. RESULTS: The cohort consists of 452 patients.
      Patient-reported outcomes improved significantly at 6 and 12 weeks. Patients
      elected to undergo surgery less than 25% of the time. Patients who decided to
      have surgery generally did so between 6 and 12 weeks, and few had surgery between
      3 and 24 months. CONCLUSION: Nonoperative treatment using this physical therapy
      protocol is effective for treating atraumatic full-thickness rotator cuff tears
      in approximately 75% of patients followed up for 2 years.

PMID- 23540578
TI  - Prediction of the location of the anterior branch of the axillary nerve, using
      correlations with physical factors: a cadaveric study.
AB  - BACKGROUND: Although axillary nerve injury is a catastrophic surgical
      complication, there is little data for precise prediction of the location of that
      nerve's anterior branch. To address that, the authors searched for a useful
      correlation between the acromion-axillary nerve distance (AAND) and one or more
      physical factors. METHODS: The heights, humeral lengths, AAND, and axillary nerve
      indexes (ANI: ratio between AAND and humeral length) of 25 male and 20 female
      cadavers were determined. Any gender differences in the mean measurements were
      determined. The correlations of each AAND with height, humeral length, and ANI
      were determined. The authors determined that using the ANI and the humeral length
      allowed the shortest prediction of the AAND. RESULTS: The mean AAND, cadaver
      height, and humeral length were 6.5 +/- 0.8, 164.9 +/- 10.0, and 33.5 +/- 2.7 cm,
      respectively. An independent t test revealed significant gender differences in
      the mean AAND (P = .003), height (P = .000), and humeral length (P = .000), but
      not in the mean ANI (P = .564). The Pearson coefficients for the associations of
      the AAND with height (r = .767), humeral length (r = .797) and ANI (r = .732)
      demonstrated strong correlations (P < .001), especially with humeral length. The
      use of the ANI with the humeral length yielded the shortest predictions of AAND,
      with a 97.8% probability of safety. CONCLUSION: There is a strong correlation
      between AAND and humeral length. In clinical practice, humeral length and ANI are
      useful for predicting the location of the anterior branch of the axillary nerve,
      when the arm is positioned at the side in neutral rotation.

PMID- 23540584
TI  - Increase nitric oxide and oxidative stress in dogs experimentally infected by
      Ehrlichia canis: effect on the pathogenesis of the disease.
AB  - The aim of this study was to evaluate nitric oxide levels, lipid peroxidation,
      protein oxidation and glutathione reductase activity in serum of dogs
      experimentally infected by Ehrlichia canis. Banked serum samples of dogs divided
      into two groups were used: negative control (n=5) and infected by E. canis (n=5).
      The concentration of nitrite/nitrate (NOx), lipid peroxidation (TBARS), advanced
      oxidation protein products (AOPP), and glutathione reductase (GR) activity in
      sera were evaluated. Samples were collected on days 0, 3, 6, 18 and 30 post
      infection (PI). NOx and TBARS levels were significantly (P<0.05) higher in the
      infected group at 18 and 30 days PI, as well as AOPP levels at 30 days PI when
      compared to samples from control group. The GR activity was significant (P<0.05)
      increased in serum of dogs infected by E. canis on days 18 and 30 PI. Based on
      the increased levels of NOx, TBARS, AOPP and GR activity we concluded that dogs
      experimentally infected by E. canis develop a state of redox imbalance and that
      these changes might be involved in the pathophysiology of the disease.

PMID- 23540585
TI  - Heart failure therapy in patients with coronary artery disease.
AB  - Heart failure and coronary artery disease share many risk factors. Coronary
      artery disease often pre-dates the development of heart failure with reduced
      ejection fraction. A diagnosis of heart failure should be considered in any
      patient with a history of coronary artery disease who presents with
      breathlessness, ankle oedema or fatigue. Several therapies, such as renin
      angiotensin antagonists and B blockers, have been proven to improve survival in
      patients with heart failure with reduced ejection fraction but evidence for
      effectiveness in heart failure with preserved ejection fraction is lacking. The
      management of heart failure and coronary artery disease overlaps considerably but
      can also be conflicting. Optimal risk factor management is key to preventing
      progression to heart failure in patients with coronary artery disease. 

PMID- 23540575
TI  - New frontiers and developing applications in 19F NMR.

PMID- 23540586
TI  - Targeting 11beta-hydroxysteroid dehydrogenases: a novel approach to manipulating
      local glucocorticoid levels with implications for rheumatic disease.
AB  - Systemic glucocorticoid excess causes osteoporosis, insulin resistance and
      central obesity. Recently it has been recognized that tissue glucocorticoid
      levels can increase independently of circulating levels. This occurs through
      increased activity of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) enzyme which is expressed in bone, synovium, liver and adipose tissue. Mice
      with global 11beta-HSD1 deletion exhibit increased severity of experimental
      arthritis. However, selective disruption of glucocorticoid signalling in
      osteoblasts and osteocytes attenuates murine experimental arthritis. In addition,
      such mice are protected against the adverse metabolic features caused by
      glucocorticoid excess. Taken together, these results indicate that bone cells,
      through local glucocorticoid signalling, are involved in the regulation of joint
      inflammation as well as systemic fuel metabolism. Clinical studies have
      demonstrated that specific inhibitors of 11beta-HSD1 improve insulin sensitivity
      and reduce weight, suggesting that inhibition of this glucocorticoid-activating
      enzyme may have applications for treating the adverse metabolic features
      associated with rheumatic disease.

PMID- 23540587
TI  - Interleukin-23: a promising therapeutic target in seronegative
      spondyloarthropathy.
AB  - Particular therapeutic challenges are raised by the spondyloarthropathies which
      represent a key area of unmet medical need. Recent investigations have shown that
      these conditions are characterised both by altered responsiveness to
      interleukin(IL)-23 and expansion of IL-23 responsive cells as well as increased
      production of IL-23. The gut in particular has emerged as a key site of IL-23
      production, and gut inflammation is known to be strongly clinically associated
      with these conditions. Moreover, HLA-B27, which is strongly associated with
      spondyloarthropathy, has also been shown to stimulate IL-23 production. The view
      is thus emerging that dysregulation of IL-23 biology is a unifying feature of
      spondyloarthropathy, suggesting that treatments targeting this cytokine are
      likely to be highly efficacious.

PMID- 23540588
TI  - Measuring listening effort expended by adolescents and young adults with
      unilateral or bilateral cochlear implants or normal hearing.
AB  - OBJECTIVES: To compare the listening effort expended by adolescents and young
      adults using implants versus their peers with normal hearing when these two
      groups are achieving similar speech perception scores. The study also aimed to
      compare listening effort expended by adolescents and young adults with bilateral
      cochlear implants when using two implants versus one. METHODS: Eight participants
      with bilateral cochlear implants and eight with normal hearing aged 10-22 years
      were included. Using a dual-task paradigm, participants repeated consonant
      nucleus-consonant (CNC) words presented in noise and performed a visual matching
      task. Signal-to-noise ratios were set individually to ensure the word perception
      task was challenging but manageable for all. Reduced performance on the visual
      task in the dual-task condition relative to the single-task condition was
      indicative of the effort expended on the listening task. RESULTS: The cochlear
      implant group, when using bilateral implants, expended similar levels of
      listening effort to the normal hearing group when the two groups were achieving
      similar speech perception scores. For three individuals with cochlear implants,
      and the group, listening effort was significantly reduced with bilateral compared
      to unilateral implants. DISCUSSION: The similar amount of listening effort
      expended by the two groups indicated that a higher signal-to-noise ratio overcame
      limitations in the auditory information received or processed by the participants
      with implants. This study is the first to objectively compare listening effort
      using two versus one cochlear implant. The results provide objective evidence
      that reduced listening effort is a benefit that some individuals gain from
      bilateral cochlear implants.

PMID- 23540589
TI  - A comparative analysis of paediatric dose-finding trials of molecularly targeted
      agent with adults' trials.
AB  - BACKGROUND: Dose-finding phase I trials in children are usually carried out once
      clinical data have already been accumulated in the adult population. The
      objectives, place and role of paediatric dose-finding trials are investigated in
      the era of molecularly targeted agents (MTAs). METHODS: Phase I paediatric
      oncology trials of MTAs approved in adults before June 15th, 2012 were reviewed.
      The recommended phase II dose (RPIID) was compared to the body surface area (BSA)
      adjusted approved dose in adults. Toxicity profile was compared to the findings
      from the corresponding adult phase I trials. RESULTS: Fifteen MTAs out of a total
      of 25 MTAs approved in the adult population have been evaluated in 19 single
      agent phase I paediatric trials. Trials included a median of 30 children with a
      median of four dose levels. The paediatric RPIID ranged between 90% and 130% of
      the BSA-adjusted approved dose in adults for 70% of the trials (75% of
      compounds). Overall, 63% of children did not receive an optimal dose. The most
      marked discrepancy involved sunitinib. Safety profiles described in phase I
      paediatric trials were usually similar to those reported in the adult population.
      CONCLUSIONS: These data suggest that dose-finding studies might not be necessary
      for all the MTAs in children. Except in the case of a narrow therapeutic index,
      early-phase trials validating pharmacokinetics, pharmacodynamic markers and
      efficacy findings from adults while controlling for toxicity appear to be a
      possible alternative to accelerate drug development in paediatric oncology.

PMID- 23540590
TI  - The beginnings of dermatopathology and dermatologic microbiology in Spain.
AB  - Crisostomo Martinez from Valencia was a pioneering microscopist in 17th-century
      Europe. The first microscopic representations of skin in Spain appeared in an
      18th-century work by Martin Martinez. Microbiology and histopathology progressed
      considerably in the late 19th century thanks to anatomists like Maestre de San
      Juan and surgeons like Federico Rubio Gali. The first Spanish pathologist to
      specialize in dermatology was Antonio Mendoza, a colleague of Jose Eugenio de
      Olavide at the Hospital San Juan de Dios in Madrid. Claudio Sala and Juan de Azua
      also made significant contributions, including the description of
      pseudoepithelioma. Several disciples of Santiago Ramon y Cajal and Jorge
      FranciscoTello, such as Lorenzo Ruiz de Arcaute and Guillermo de la Rosa King,
      consolidated the dermatology laboratory, but the Civil War sent many into exile
      or deprived them of their professional status. Juan Rubio in Barcelona and Julio
      Rodriguez Puchol in Madrid were the immediate predecessors of today's
      dermatopathologists. 

PMID- 23540592
TI  - Ulcerated giant pilomatrixoma in a child.

PMID- 23540593
TI  - Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.
AB  - Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which
      is found in both normal and neoplastic B cells. In recent years, it has been
      increasingly used to treat cutaneous B-cell lymphoma and is now considered an
      alternative to classic treatment (radiotherapy and surgery) of 2 types of
      indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary
      cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an
      alternative to polychemotherapy in the treatment of primary cutaneous large B
      cell lymphoma, leg type. Its use as an alternative drug led to it being
      administered intralesionally, with beneficial effects. In the present article, we
      review the literature published on the use of rituximab to treat primary
      cutaneous B-cell lymphoma. 

PMID- 23540594
TI  - Bullous pemphigoid: clinical practice guidelines.
AB  - Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease in which
      autoantibodies are directed against components of the basement membrane. Most of
      these antibodies belong to the immunoglobulin G class and bind principally to 2
      hemidesmosomal proteins: the 180-kD antigen (BP180) and the 230-kD antigen
      (BP230). It is the most common blistering disease in the adult population in
      developed countries, with an estimated incidence in Spain of 0.2 to 3 cases per
      100,000 inhabitants per year. The disease primarily affects older people,
      although it can also occur in young people and even in children. In recent years,
      advances in clinical practice have led to a better understanding and improved
      management of this disorder. These advances include new diagnostic techniques,
      such as enzyme-linked immunosorbent assay for BP180 and new drugs for the
      treatment of BP, with diverse therapeutic targets. There is, however, still no
      international consensus on guidelines for the management of BP. This article is
      an updated review of the scientific literature on the treatment of BP. It focuses
      primarily on evidence-based recommendations and is written from a practical
      standpoint based on experience in the routine management of this disease. 

PMID- 23540595
TI  - Whitish plaque on the soft palate.

PMID- 23540596
TI  - Comprehensive care of amyotrophic lateral sclerosis patients: a care model.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      that presents with muscle weakness, causing progressive difficulty in movement,
      communication, eating and ultimately, breathing, creating a growing dependence on
      family members and other carers. The ideal way to address the problems associated
      with the disease, and the decisions that must be taken, is through
      multidisciplinary teams. The key objectives of these teams are to optimise
      medical care, facilitate communication between team members, and thus to improve
      the quality of care. In our centre, we have extensive experience in the care of
      patients with ALS through an interdisciplinary team whose aim is to ensure proper
      patient care from the hospital to the home setting. In this article, we describe
      the components of the team, their roles and our way of working. 

PMID- 23540597
TI  - Primary research on unrelated double umbilical cord blood transplantation and
      implantation kinetics.
AB  - OBJECTIVE: This study sought to examine implantation and implantation kinetics in
      double umbilical cord blood transplantation (DUCBT). METHODS: Twenty-nine
      patients who underwent a two-unit unrelated donor cord blood transplantation were
      included in this study. After transplantation, hematopoietic chimerism of the
      peripheral blood was evaluated based on the results of short tandem repeat
      polymerase chain reaction. Using these results, we were able to judge whether the
      transplanted cells implanted, determine which donor's cells implanted, and
      further examine the kinetics of implantation in DUCBT. The numbers of total
      nucleated cells (TNCs), CD34(+) cells, colony forming units (CFUs), colony
      forming unit-granulocytes and macrophages (CFU-GMs), and CD3(+) cells were
      compared between the dominant units and the non-dominant units in an attempt to
      understand the discipline and implantation kinetics of DUCBT. RESULTS: Neither
      the TNC counts nor the counts of CD34(+) cells, CFU, CFU-GM, or CD3(+) cells were
      significantly different between the dominant units and the non-dominant units (P
      values of 0.584, 0.322, 0.842, 0.534, and 0.082, respectively). CONCLUSIONS: We
      were able to determine the engraftment status at 14 days after DUCBT, although
      the implantation kinetics of DUCBT remain uncharacterized and require further
      research.

PMID- 23540598
TI  - Whole-organism high-throughput screening against Trypanosoma brucei brucei.
AB  - INTRODUCTION: Human African trypanosomiasis (HAT) occurs as a result of infection
      with the protozoan parasites Trypanosoma brucei gambiense and T.b. rhodesiense
      and is nearly always fatal without treatment. However, current therapeutic
      options are severely limited and there is a desperate need for new compounds to
      treat the disease. Whole-cell high-throughput screening (HTS) is a technique
      frequently used to identify compounds with trypanocidal activity. AREAS COVERED:
      The authors examine the development of whole-organism HTS assays for T.b. brucei.
      The authors describe the successes achieved through HTS and discuss the
      advantages and disadvantages of whole-organism HTS. EXPERT OPINION: Despite
      hundreds of trypanocidal molecules being identified by whole-organism HTS, very
      few have progressed into preclinical development. The failure of molecules
      identified by HTS to progress along the drug development pathway is due to a
      multitude of factors including undrug-like molecules and molecules having poor
      pharmacodynamics/kinetic properties. Future studies should focus on screening
      libraries that contain drug-like molecules that possess some of the properties
      required in the final compound.

PMID- 23540599
TI  - Effect of traumatic imagery on cerebrospinal fluid dopamine and serotonin
      metabolites in posttraumatic stress disorder.
AB  - Dopaminergic mechanisms may be involved in the pathophysiology of posttraumatic
      stress disorder (PTSD), although the evidence for this is limited; serotonergic
      mechanisms are implicated largely by virtue of the modest efficacy of
      serotonergic drugs in the treatment of the disorder. Basal cerebrospinal fluid
      (CSF) dopamine and serotonin metabolite concentrations are normal in PTSD
      patients. However, in the present experiment, we postulated that perturbations in
      CSF dopamine and serotonin metabolites could be induced by acute psychological
      stress. Ten volunteers with war-related chronic PTSD underwent 6-h continuous
      lumbar CSF withdrawal on two occasions per patient (6-9 weeks apart), using a
      randomized, within subject-controlled, crossover design. During one session a 1-h
      video with trauma-related footage (traumatic video) was shown and in the other
      session subjects viewed a 1-h neutral video. We quantified the dopamine
      metabolite homovanillic acid (HVA) and the serotonin metabolite 5
      hydroxyindoleacetic acid (5-HIAA) in CSF at 10-min intervals, before, during, and
      after video provocation. Blood pressure, heart rate, and subjective anxiety and
      mood were monitored. Significant drop in mood and increases in anxiety and blood
      pressure occurred during the traumatic relative to the neutral movie. CSF HVA
      concentrations diminished significantly after the traumatic video (p < 0.05), in
      comparison with the neutral, while 5-HIAA tended to diminish (p < 0.10). We
      conclude that an acute decline in CNS HVA concentrations is associated with
      laboratory-induced symptoms in chronic PTSD patients. While further research is
      required to determine if the stress-induced dopaminergic changes are normative or
      pathological, the present data suggest that increasing dopaminergic
      neurotransmission be explored as a potential therapy, or adjunctive therapy, for
      PTSD.

PMID- 23540600
TI  - Analysis of Sp transcription factors in the postmortem brain of chronic
      schizophrenia: a pilot study of relationship to negative symptoms.
AB  - Negative symptoms are the most resilient manifestations in schizophrenia. An
      imbalance in dopamine and glutamate pathways has been proposed for the emergence
      of these symptoms. SP1, SP3 and SP4 transcription factors regulate genes in these
      pathways, suggesting a possible involvement in negative symptoms. In this study,
      we characterized Sp factors in the brains of subjects with schizophrenia and
      explored a possible association with negative symptoms. We also included analysis
      of NR1, NR2A and DRD2 as Sp target genes. Postmortem cerebellum and prefrontal
      cortex from an antemortem clinically well-characterized and controlled collection
      of elderly subjects with chronic schizophrenia (n = 16) and control individuals
      (n = 14) were examined. We used the Positive and Negative Syndrome and the
      Clinical Global Impression Schizophrenia scales, quantitative PCR and immunoblot.
      SP1 protein and mRNA were reduced in the prefrontal cortex in schizophrenia
      whereas none of Sp factors were altered in the cerebellum. However, we found that
      SP1, SP3 and SP4 protein levels inversely correlated with negative symptoms in
      the cerebellum. Furthermore, NR2A and DRD2 mRNA levels correlated with negative
      symptoms in the cerebellum. In the prefrontal cortex, SP1 mRNA and NR1 and DRD2
      inversely correlated with these symptoms while Sp protein levels did not. This
      pilot study not only reinforces the involvement of SP1 in schizophrenia, but also
      suggests that reduced levels or function of SP1, SP4 and SP3 may participate in
      negative symptoms, in part through the regulation of NMDA receptor subunits
      and/or Dopamine D2 receptor, providing novel information about the complex
      negative symptoms in this disorder.

PMID- 23540601
TI  - Sc(OTf)3-catalyzed dehydrogenative cyclization for synthesis of N
      methylacridones.
AB  - A novel method has been developed for the synthesis of substituted N
      methylacridones from 2-(N-methyl-N-phenylamino)benzaldehydes via dehydrogenative
      cyclization. This transformation involves two primary processes: the aldehyde
      first coordinates with Sc(OTf)3 and induces the aromatic electrophilic
      substitution (S(E)Ar) reaction to form the active intermediate N-methyl-acridin-9
      ol, which is then quickly oxidized in situ to afford the acridones. Furthermore,
      the procedure involved is both environmental friendly and atom efficient; H2O is
      the only byproduct in this reaction.

PMID- 23540602
TI  - Aptamer-modified micro/nanostructured surfaces: efficient capture of Ramos cells
      in serum environment.
AB  - For potential applications in the isolation and enrichment of circulating tumor
      cells (CTCs), we have developed gold nanoparticle layers (GNPLs) of different
      roughness modified with TD05 aptamers (GNPL-APT). In serum-free binary cell
      mixtures containing Ramos cancer cells and CEM cells, the density of Ramos cells
      adherent to highly rough GNPL-APT was 19 times that of CEM cells. However, in
      serum-containing conditions, the specificity of GNPL-APT for Ramos cells was much
      reduced. To improve Ramos specificity in the presence of serum, we attached the
      TD05 aptamer to the layers via poly(oligo(ethylene glycol) methacrylate) (POEGMA)
      as an antifouling spacer (GNPL-POEGMA-APT). In serum-containing environment GNPL
      POEGMA-APT showed an enhanced selectivity for Ramos cells, which increased with
      increasing surface roughness. The results of this study indicate that surfaces
      combining appropriate chemical composition and micro/nano roughness structures
      may be useful for cell separation, including the isolation of cancer cells for
      diagnosis.

PMID- 23540603
TI  - Cantilevered-capillary force apparatus for measuring multiphase fluid
      interactions.
AB  - A new instrument is presented for investigating interactions between individual
      colloidal particles, emulsion droplets, foam bubbles, and other particle-particle
      or particle-surface interactions. Measurement capabilities are demonstrated by
      measuring interfacial tension, coalescence time for emulsion droplets, adhesion
      between giant multilamellar vesicles, and adhesion between model food emulsion
      particles. The magnitude of the interaction force that can be measured or
      imposed, ranges from 1 nN to 1 mN for particles ranging in size from 10 MUm to 1
      mm in diameter.

PMID- 23540604
TI  - Effect of breed, sex, age and body weight on echocardiographic measurements in
      the equine species.
AB  - Little is known about the effect of various animal's signalment variables on
      echocardiographic reference values in the equine species. This study was
      performed to evaluate the effect of sex, breed, age and body weight (BW) on
      echocardiographic measurements in the equine species. Echocardiography was
      performed on 212 ponies or horses of various breeds, aged from 1 day to 37 years
      old (mean+/-SD: 7.8 +/- 5.8 years), BW 38-890 kg (mean +/- SD: 421 +/- 133 kg),
      and free of cardiac disease. Fifty of those animals aged from 2 months to 35
      years old (mean +/- SD: 11.6 +/- 6.4 years old); BW 77-662 kg (mean +/- SD: 436
      +/- 135 kg) were also examined using the pulsed-wave Doppler mode. Standard two
      dimensional and M-mode echocardiography were performed on all animals. Standard
      pulsed-wave Doppler examination of each cardiac valve was performed on the 50
      first examined animals. Data were analysed using a general linear model including
      the effect of sex, age, breed and BW after logarithmic transformation of the
      data. Therefore, the same analysis was performed separately on animals aged <= 2
      years-old and on older animals. All dimensional echocardiographic measurements
      were significantly affected by BW and most of them were significantly affected by
      breed, but not by sex. Only the aortic and the pulmonary artery internal diameter
      were significantly affected by age. None of the Doppler measurements were
      significantly affected by the tested variables. In conclusion, in the equine
      species, dimensional echocardiographic reference values should be established
      using regression equations as a function of BW, which could increase the
      diagnostic value of this leading technique in equine cardiology. Breed could also
      have an effect on those measurements.

PMID- 23540605
TI  - Cellular and humoral immunogenicity of Mycobacterium avium subsp.
      paratuberculosis specific lipopentapeptide antigens.
AB  - Paratuberculosis caused by Mycobacterium avium subsp. paratuberculosis (MAP) is a
      chronic infectious disease affecting domestic and wild ruminants. Antigens
      currently used for the diagnosis of paratuberculosis are whole-cell derived crude
      preparations. The identification of MAP-specific antigens for the specific and
      early diagnosis of this infection is strongly needed. This study assessed the
      ability of the MAP-specific synthetic lipopeptide antigen Para-LP-01 to invoke
      specific serum antibody (Ab) and cell-mediated immune (CMI) responses in sheep
      experimentally exposed to MAP S strain. Responses were compared to those elicited
      by the crude whole-cell derived MAP 316v antigen (316v). Para-LP-01 induced a
      significant serum Ab response in MAP-infected sheep in comparison with unexposed
      or uninfected sheep, but failed to induce detectable CMI responses including
      production of IFN-gamma, IL-10 and lymphoproliferation, unlike 316v which invoked
      both CMI and serum Ab responses in MAP-exposed sheep. Para-LP-01 is a suitable
      antigen for serodiagnosis of MAP-infection in sheep. The differential induction
      of humoral and CMI responses by lipid based antigens could enhance current
      understanding of the role played by cell-wall associated lipid antigens in the
      pathogenesis of MAP-infection.

PMID- 23540606
TI  - Short communication: acute phase proteins in Holstein cows diagnosed with uterine
      infection.
AB  - The aim of this work was to monitor the pattern of serum acute phase proteins
      [paraoxonase (PON), haptoglobin (Hp) and albumin] during the peripartum period of
      normal healthy cows (n=16) compared to that in cows diagnosed with uterine
      infection (n=15). Albumin concentrations were lower at 21 days before expected
      calving in cows subsequently diagnosed with uterine infection and predicted the
      occurrence of uterine infection with an accuracy of 79.3%. Cows diagnosed with
      uterine infection had a postpartum reduction in serum PON activity and the
      concentration of Hp increased at 7 DIM for multiparous uterine infected cows. In
      conclusion, cows diagnosed with uterine infection had reduced serum albumin
      concentration 21 days before calving, lower PON activity at 7 days after calving,
      and increased Hp in multiparous cows at 7 DIM compared to healthy cows.

PMID- 23540607
TI  - Effects of sodium selenite on the decreased percentage of T cell subsets,
      contents of serum IL-2 and IFN-gamma induced by aflatoxin B1 in broilers.
AB  - Aflatoxin B1 (AFB1), especially inducing hepatocellular carcinoma and
      immunosuppression of animals, poses a serious healthy and economic hazard to both
      humans and livestock. Animal studies have demonstrated that selenium (Se)
      provides anticarcinogenic and antimutagenic effects against AFB1. However, the
      effects of Se against AFB1-induced immunosuppression were rarely reported. To
      test this, three hundred 1-day-old male avian broilers were divided into five
      groups and fed on control diet (0.4 mg/kg Se), AFB1 group(0.3mg/kg AFB1+0.4 mg/kg
      Se), AFB1+Se group I(0.3mg/kg AFB1+0.6 mg/kg Se), AFB1+Se group II(0.3mg/kg
      AFB1+0.8 mg/kg Se) and AFB1+Se group III(0.3mg/kg AFB1+1.0mg/kg Se) for 21 days
      (n=60/group). Although the body weight in AFB1 group was lower than that in
      control group at 14 days of age, there no significant differences on body weight
      among five groups at 7 and 21 days of age. No evident clinical symptoms were
      observed among five groups from 7 to 21 days of age. The percentages of
      peripheral blood CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and the contents of serum IL
      2 and IFN-gamma in AFB1 group were decreased, compared with those in control
      group. Compared with those in AFB1 group, the percentages of CD3(+), CD3(+)CD4(+)
      and CD3(+)CD8(+) T cells in three AFB1+Se groups were increased from 14 to 21
      days of age, and the contents of serum IL-2 and IFN-gamma in all AFB1+Se groups
      were increased from 7 to 21 days of age. On the contrary, the percentages of
      CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) T cells, and the contents of Serum IL-2 and
      IFN-gamma in AFB1+Se group III were lower than those in AFB1+Se group II. It was
      concluded that 0.6 and 0.8 mg/kg Se could increase the decreased percentages of
      peripheral blood T-cell subsets and the contents of serum IL-2 and IFN-gamma
      induced by 0.3mg/kg AFB1 in the diets, and cellular immune function could be
      improved in chickens.

PMID- 23540608
TI  - Methadone in healthy goats - pharmacokinetics, behaviour and blood pressure.
AB  - The pharmacokinetics and effects of the opioid methadone on behaviour, arterial
      blood pressure, heart rate and haematocrit were studied in goats. Two goats
      received methadone (0.2mg/kg) intravenously and the terminal half-life was 88 and
      91 min, the volume of distribution 8.4 and 6.1L/kg, and clearance 86 and 123
      mL/min/kg. In a crossover study eight goats received methadone (0.6 mg/kg) or
      0.15M NaCl subcutaneously (SC). After SC administration bioavailability was
      complete and the terminal half-life was 215 +/- 84 min (mean +/- SD), Tmax 31 +/-
      15 min and Cmax 45 +/-11 ng/mL. Blood pressure and haematocrit increased while
      heart rate did not change. The goats did not ruminate and they climbed,
      scratched, gnawed and showed tail-flicking after SC methadone in contrast to NaCl
      administration. The use of methadone in goats may be restricted due to the
      inhibition of rumination and the rather short half-life.

PMID- 23540610
TI  - In vitro maturation remains an interesting procedure.
AB  - The number of live births from IVM oocytes has been increasing over the past two
      decades. Data concerning the health of IVM infants are reported by the authors of
      this Views and Reviews.

PMID- 23540609
TI  - Molar mass, entanglement, and associations of the biofilm polysaccharide of
      Staphylococcus epidermidis.
AB  - Biofilms are microbial communities that are characterized by the presence of a
      viscoelastic extracellular polymeric substance (EPS). Studies have shown that
      polysaccharides, along with proteins and DNA, are a major constituent of the EPS
      and play a dominant role in mediating its microstructure and rheological
      properties. Here, we investigate the possibility of entanglements and associative
      complexes in solutions of extracellular polysaccharide intercellular adhesin
      (PIA) extracted from Staphylococcus epidermidis biofilms. We report that the
      weight average molar mass and radius of gyration of PIA isolates are 2.01*10(5)+/
      1200 g/mol and 29.2+/-1.2 nm, respectively. The coil overlap concentration, c*,
      was thus determined to be (32+/-4)*10(-4) g/mL. Measurements of the in situ
      concentration of PIA (cPIA,biofilm) was found to be (10+/-2)*10(-4) g/mL.Thus,
      cPIA,biofilm<c* and the amount of PIA in the biofilm is too low to cause polymer
      chain entanglements. In the pH range 3.0-5.5, PIA was found to both self
      associate and to form complexes with bovine serum albumin (BSA). By static light
      scattering, both self-association and complex formation with 0.5% (w/v) BSA were
      found to occur at PIA concentrations of 0.30*10(-4) g/mL and greater, which is
      about 30 times lower than the measured cPIA,biofilm. These results suggest that
      the microscopic origin of EPS viscoelasticity is unlikely to be due to
      polysaccharide entanglements. Furthermore, the onset of self-association and
      protein complexation of PIA occurs at concentrations far lower than the native
      PIA concentration in biofilms. This finding therefore suggests a critical role
      for those two association mechanisms in mediating biofilm viscoelasticity.

PMID- 23540611
TI  - Is the nuclear status of an embryo an independent factor to predict its ability
      to develop to term?
AB  - OBJECTIVE: To determine the prognostic impact of the embryo nuclear status at day
      2 among other major morphologic parameters (first cleavage at day 1, number of
      blastomeres and anuclear fragmentation at day 2) on the birth rate. DESIGN:
      Retrospective study. SETTING: Hospital IVF department. PATIENT(S): Women
      undergoing 1,629 day 2 transfers of 2,732 embryos from May 2006 to November 2008.
      INTERVENTION(S): Four groups according to the embryo nuclear status. MAIN OUTCOME
      MEASURE(S): Implantation, miscarriage, and birth rates. RESULT(S): Univariate
      analysis indicated significantly higher birth rates when all blastomeres were
      mononucleated (15.0%) compared with embryos with not all blastomeres
      mononucleated (9.2%), embryos without any visible nucleus (7.7%), and embryos
      where at least one blastomere was multinucleated (4.2%). Multivariate analysis
      found significant decreased birth rates when multinucleated blastomeres were
      observed. CONCLUSION(S): Blastomere nuclear status should be added to the kinetic
      and morphologic criteria traditionally used at day 2 to assess human embryo
      quality. The presence of multinucleated blastomeres has a negative impact on
      birth potential. The results argue for integrating the blastomere nuclear status
      at day 2 with the kinetic and morphologic criteria traditionally used to define
      the best embryo to transfer. Embryos with a single visible nucleus in all
      blastomeres should be given priority for transfer when available.

PMID- 23540612
TI  - Mauriac syndrome still exists.
AB  - BACKGROUND/OBJECTIVE: Mauriac syndrome (MS) is a rare complication of type 1
      diabetes mellitus (DM1). It is related to low insulin concentrations and is less
      common since longer-acting insulins became available. It is characterized by
      hepatomegaly, growth and puberty delay, and the presence of elevated
      transaminases and serum lipids. The aim of this study was to describe the
      patients from a pediatric diabetic population that fulfill the criteria of MS.
      MATERIALS AND METHODS: A retrospective analysis of the pediatric diabetic
      population with diagnostic criteria of MS currently followed at Hospital de
      Braga, was performed. RESULTS: From a population of 91 patients with DM1 18
      years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy.
      The age at presentation was 13-17 years, with a minimum interval between DM1
      diagnosis and MS criteria of 4 years. All the patients were prescribed intensive
      insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous
      history of poor glycemic control before the diagnosis of MS with glycated
      hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present
      in all the patients; 4 of them had associated hepatomegaly. All the girls
      presented puberty delay and cushingoid features. None of the patients presented
      short stature and 5 of them presented mixed dyslipidemia. CONCLUSIONS: Although
      MS is an ancient entity described in DM1, it still exists, particularly in
      adolescent females. Being aware of MS is of extreme importance since most of the
      clinical features are reversible with better glycemic control.

PMID- 23540613
TI  - [Management of severe amiodarone-induced thyrotoxicosis after failure of standard
      medical treatment].

PMID- 23540614
TI  - Adrenal carcinoma: a retrospective analysis of our series.

PMID- 23540617
TI  - Controversies in IgG replacement therapy in patients with antibody deficiency
      diseases.
AB  - This Current perspectives article will review and highlight the importance of
      accurate diagnosis of patients who have failed to produce specific antibodies to
      naturally encountered foreign proteins or polysaccharides or after vaccination
      and the appropriate institution of immunoglobulin replacement therapy. The field
      of primary immunodeficiency disease (PIDD) has expanded remarkably since the
      early descriptions 6 decades ago. With greater recognition and advanced cellular
      and molecular diagnostic technology, new entities and single-gene defects in
      patients with PIDD are rapidly being defined. This, combined with treatment
      advances and newborn screening for severe combined immunodeficiency, has resulted
      in improved outcomes and survival and even permanent cures. Awareness of PIDD has
      also increased, but the guidelines for recognition remain to be validated. The
      zeal for registering and enrolling patients has potentially created a large body
      of "patients" treated with immunoglobulin replacement unnecessarily. The
      complexity, diversity, and availability of laboratory testing have brought
      awareness of PIDD to the forefront, but because of an absence of standardization
      of certain assays, concerns about the correct diagnosis and appropriate treatment
      have increased. We hope to refocus the discussion on identifying clear laboratory
      and clinical guidelines for the establishment of an accurate diagnosis of
      antibody deficiency, its rationale, and, where indicated, institution of safe
      treatment.

PMID- 23540619
TI  - Development of skin lesions in filaggrin-deficient mice is dependent on adaptive
      immunity.

PMID- 23540620
TI  - Host-microbial interactions in patients with chronic rhinosinusitis.

PMID- 23540616
TI  - Genetics of chronic rhinosinusitis: state of the field and directions forward.
AB  - The cause of chronic rhinosinusitis (CRS) remains unclear. Study of the genetic
      susceptibility to CRS might be a valuable strategy to understand the pathogenesis
      of this burdensome disorder. The purpose of this review is to critically evaluate
      the current literature regarding the genetics of CRS in a comprehensive fashion.
      The most promising findings from candidate gene studies include the cystic
      fibrosis transmembrane conductance regulator gene (CFTR), as well as genes
      involved in antigen presentation, innate and adaptive immune responses, tissue
      remodeling, and arachidonic acid metabolism. We also review the few hypothesis
      independent genetic studies of CRS (ie, linkage analysis and pooling-based genome
      wide association studies). Interpretation of the current literature is limited by
      challenges with study design, sparse replication, few functional correlates of
      associated polymorphisms, and inadequate examination of linkage disequilibrium or
      expression quantitative trait loci for reported associations. Given the
      relationship of CRS to other airway disorders with well-characterized genetic
      components (eg, asthma), study of the genetics of CRS deserves increased
      attention and investment, including the organization of large, detailed, and
      collaborative studies to advance knowledge of the mechanisms that underlie this
      disorder.

PMID- 23540615
TI  - B-lymphocyte lineage cells and the respiratory system.
AB  - Adaptive humoral immune responses in the airways are mediated by B cells and
      plasma cells that express highly evolved and specific receptors and produce
      immunoglobulins of most isotypes. In some cases, such as autoimmune diseases or
      inflammatory diseases caused by excessive exposure to foreign antigens, these
      same immune cells can cause disease by virtue of overly vigorous responses. This
      review discusses the generation, differentiation, signaling, activation, and
      recruitment pathways of B cells and plasma cells, with special emphasis on unique
      characteristics of subsets of these cells functioning within the respiratory
      system. The primary sensitization events that generate B cells responsible for
      effector responses throughout the airways usually occur in the upper airways,
      tonsils, and adenoid structures that make up the Waldeyer ring. On secondary
      exposure to antigen in the airways, antigen-processing dendritic cells migrate
      into secondary lymphoid organs, such as lymph nodes, that drain the upper and
      lower airways, and further B-cell expansion takes place at those sites. Antigen
      exposure in the upper or lower airways can also drive expansion of B-lineage
      cells in the airway mucosal tissue and lead to the formation of inducible
      lymphoid follicles or aggregates that can mediate local immunity or disease.

PMID- 23540623
TI  - Differential expression of members of the IGF system in OPU-derived oocytes from
      Nelore (Bos indicus) and Holstein (Bos taurus) cows.
AB  - The insulin-like growth factor (IGF) system is related to quality of oocytes and
      embryos. The aim of this study was to investigate the mRNA levels of IGF1 and
      IGF2 and their receptors, IGFR1 and IGFR2, as well as IGFBP2, IGFBP4, and PAPP-A
      in oocytes from Nelore compared to Holstein cows. Pools of oocytes (20
      oocytes/pool) from Nelore (n=8 pools) and Holstein (n=4 pools) were obtained via
      ovum pick-up (OPU, 10 sessions) and cumulus cells and zona pellucida were
      removed. The pools were submitted to total RNA extraction. Expression of members
      of the IGF system was assessed by real time RT-PCR. The mRNA expression of IGF1
      and IGF2, IGFR1 and IGFR2, IGFBP2 and IGFBP4 was significantly higher (P<0.01) in
      oocytes from Holstein whereas the expression of PAPP-A was significantly higher
      (P<0.05) in oocytes from Nelore cows. The high PAPP-A expression and the low
      expression of IGFBP2 and IGFBP4 are associated with more efficient degradation of
      IGFBPs, which results in greater bioavailability of IGF in Nelore oocytes when
      compared to the Holstein.

PMID- 23540624
TI  - Electrode location and clinical outcome in hippocampal electrical stimulation for
      mesial temporal lobe epilepsy.
AB  - PURPOSE: To study the clinical outcome in hippocampal deep brain stimulation
      (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy
      (MTLE) according to the electrode location. METHODS: Eight MTLE patients
      implanted in the hippocampus and stimulated with high-frequency DBS were included
      in this study. Five underwent invasive recordings with depth electrodes to
      localize ictal onset zone prior to chronic DBS. Position of the active contacts
      of the electrode was calculated on postoperative imaging. The distances to the
      ictal onset zone were measured as well as atlas-based hippocampus structures
      impacted by stimulation were identified. Both were correlated with seizure
      frequency reduction. RESULTS: The distances between active electrode location and
      estimated ictal onset zone were 11+/-4.3 or 9.1+/-2.3mm for patients with a >50%
      or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure
      frequency reduction, 100% had the active contacts located <3mm from the subiculum
      (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm
      to the subiculum. CONCLUSION: Decrease of epileptogenic activity induced by
      hippocampal DBS in refractory MTLE: (1) seems not directly associated with the
      vicinity of active electrode to the ictal focus determined by invasive
      recordings; (2) might be obtained through the neuromodulation of the subiculum.

PMID- 23540625
TI  - Bisphenol-A and residual monomer leaching from orthodontic adhesive resins and
      polycarbonate brackets: a systematic review.
AB  - INTRODUCTION: The objective of this systematic review was to assess the short-
      and long-term release of components of orthodontic adhesives and polycarbonate
      brackets in the oral environment. METHODS: Electronic database searches of
      published and unpublished literature were performed. The following electronic
      databases with no language and publication date restrictions were searched:
      MEDLINE (via Ovid and PubMed), EMBASE (via Ovid), Cochrane Oral Health Group's
      Trials Register, and CENTRAL. Unpublished literature was searched on
      ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation
      Abstracts and Thesis database. The reference lists of all eligible studies were
      checked for additional studies. Two review authors performed data extraction
      independently and in duplicate using data collection forms. Disagreements were
      resolved by discussion or the involvement of an arbiter. RESULTS: No randomized
      controlled trial was identified. In the absence of randomized controlled trials,
      observational studies were included. Eleven studies met the inclusion criteria.
      All were observational studies conducted in vivo or in vitro. The bisphenol-A
      release from orthodontic bonding resins was found to be between 0.85 and 20.88 ng
      per milliliter in vivo, and from traces to 65.67 ppm in vitro. Polycarbonate
      brackets released amounts of 22.24 MUg per gram in ethanol solution and 697 MUg
      per gram after 40 months in water. Bis-GMA and TEGDMA leaching in vitro reached
      levels of 64 and 174 mg per 10 MUL, respectively. Because of the heterogeneity in
      methodologies and reporting, only qualitative synthesis was performed.
      CONCLUSIONS: The available evidence on this topic derived from observational in
      vivo and in-vitro studies that represent a moderate level of evidence. The
      variety of setups and the different units allied to the diversity of reporting
      among studies did not allow calculation of pooled estimates.

PMID- 23540626
TI  - In-vitro vs in-vivo materials research.

PMID- 23540627
TI  - Indirect usage of miniscrew anchorage to intrude overerupted mandibular incisors
      in a Class II patient with a deep overbite.
AB  - Vertical dentoalveolar discrepancies are a common problem in orthodontic patients
      but are often difficult to treat with traditional mechanics. This case report
      illustrates the successful treatment of overerupted mandibular incisors via the
      indirect use of miniscrew anchorage. A woman (age, 22 years 9 months) had chief
      complaints of maxillary incisor protrusion and crooked teeth. An excessive curve
      of Spee caused by elongation of the mandibular incisors was also found. The
      patient was diagnosed with a severe Class II Division 1 malocclusion and a deep
      overbite. After extraction of the mandibular first premolars and the subsequent
      leveling phase, the elongated incisors were intruded with a novel method, which
      involved the combined use of sectional archwires and miniscrews placed in the
      premolar areas. After the procedure, the mandibular incisors had been intruded by
      6.5 mm with no undesirable side effects. The total active treatment period was 42
      months. The resultant occlusion and satisfactory facial profile were maintained
      after 30 months of retention. Our novel intrusion approach shows potential for
      correcting a deep overbite.

PMID- 23540628
TI  - Ethics in orthodontics. You make the decision.

PMID- 23540629
TI  - Treatment of anterior open bite and multiple missing teeth with lingual fixed
      appliances, double jaw surgery, and dental implants.
AB  - The treatment of adult patients with severe anterior open bite frequently
      requires orthognathic surgery, especially when the chin is retruded severely. If
      a patient has multiple missing posterior teeth, it is difficult to control the
      occlusal plane because it is challenging to obtain anchorage during orthodontic
      treatment. We report on a 25-year-old woman who had a skeletal Class II
      malocclusion, severe anterior open bite, vertical maxillary asymmetry, and severe
      dental caries on her molars. There was no posterior occlusal contact between the
      maxillary and mandibular molars since 5 of her molars had to be extracted because
      of severe caries. Lingual fixed appliances and double jaw surgery were performed
      to treat her skeletal and dental problems, and dental implants helped restore her
      masticatory function. Pretreatment, posttreatment, and retention photographs
      demonstrate effective, esthetically pleasing, and stable treatment results.

PMID- 23540631
TI  - Severe open bite due to traumatic condylar fractures treated nonsurgically with
      implanted miniscrew anchorage.
AB  - This case report illustrates the use of miniscrews to treat a patient with an
      open bite caused by mandibular condylar fractures. The patient was 36 years old
      when she visited our hospital with a chief complaint of difficulty with chewing.
      She had suffered condylar and maxillary bone fractures in a traffic accident 6
      months before her visit. She had an anterior open bite and Angle Class II molar
      relationships. Her mandibular midline was deviated to the right relative to the
      maxilla. The cephalometric analysis showed a skeletal Class II relationship.
      Titanium miniscrews were implanted in the bilateral maxillary buccal areas. The
      maxillary dentition was retracted and intruded by using elastomeric chains and
      miniscrews. After this treatment, an Angle Class I molar relationship was
      achieved, her overjet and overbite became ideal, and a good facial appearance was
      obtained. The total active orthodontic treatment period was 33 months. Treating
      an open bite with molar intrusion often leads to counterclockwise rotation of the
      mandible; however, in this patient, the mandible was moved anteriorly and upward.
      We believe that this movement was caused by the patient's condylar fractures and
      the subsequent remodeling. Although there was some relapse, our results suggest
      that implant anchorage is useful for correcting anterior open bites originating
      from condylar fractures.

PMID- 23540632
TI  - Combined multisegmental surgical-orthodontic treatment of bialveolar protrusion
      and chin retrusion with severe facial asymmetry.
AB  - LeFort I osteotomy, anterior segmental osteotomy, bilateral sagittal split ramus
      osteotomy, and genioplasty are frequently used methods for correcting facial
      deformities. However, in patients with an abnormally shaped maxilla or mandible,
      more complex surgical techniques or multiple combinations must be considered for
      improved esthetic results. This article presents a patient with bialveolar
      protrusion, mandibular prognathism, chin retrusion, a long face, and severe
      facial asymmetry. A combination of LeFort I asymmetric impaction, anterior
      segmental osteotomy, and 3-piece segmentation of the maxilla, and bilateral
      sagittal split ramus osteotomy, anterior segmental osteotomy, genioplasty
      advancement, and angle shaving in the mandible were conducted simultaneously. In
      patients with complicated deformities that cannot be classified by simple
      conventional classification methods, multisegmental osteotomy can be an option
      for improved esthetic results.

PMID- 23540633
TI  - Selecting custom torque prescriptions for the straight-wire appliance.
AB  - Selecting custom torque prescriptions based on the treatment needs of each
      patient can reduce the amount of routine archwire torque adjustment needed and
      speed torque correction, thus reducing the total treatment time. Using the
      appropriate torque prescription prevents iatrogenic torque problems and allows
      most torque corrections to be done earlier with more resilient nickel-titanium
      and beta-titanium wires. As a result, fewer time-consuming final torque
      adjustments are needed with stainless steel finishing wires, resulting in shorter
      treatment time.

PMID- 23540634
TI  - Quantitative comparison of 3 enamel-stripping devices in vitro: how precisely can
      we strip teeth?
AB  - INTRODUCTION: In this in-vitro study, we aimed to investigate the predictability
      of the expected amount of stripping using 3 common stripping devices on
      premolars. METHODS: One hundred eighty extracted premolars were mounted and
      aligned in silicone. Tooth mobility was tested with Periotest (Medizintechnik
      Gulden, Modautal, Germany) (8.3 +/- 2.8 units). The selected methods for
      interproximal enamel reduction were hand-pulled strips (Horico, Hapf Ringleb &
      Company, Berlin, Germany), oscillating segmental disks (O-drive-OD 30; KaVo
      Dental, Biberach, Germany), and motor-driven abrasive strips (Orthofile; SDC
      Switzerland, Lugano-Grancia, Switzerland). With each device, the operator
      intended to strip 0.1, 0.2, 0.3, or 0.4 mm on the mesial side of 15 teeth. The
      teeth were scanned before and after stripping with a 3-dimensional laser scanner.
      Superposition and measurement of stripped enamel on the most mesial point of the
      tooth were conducted with Viewbox software (dHal Software, Kifissia, Greece). The
      Wilcoxon signed rank test and the Kruskal-Wallis test were applied; statistical
      significance was set at alpha <= 0.05. RESULTS: Large variations between the
      intended and the actual amounts of stripped enamel, and between stripping
      procedures, were observed. Significant differences were found at 0.1 mm of
      intended stripping (P <= 0.05) for the hand-pulled method and at 0.4 mm of
      intended stripping (P <= 0.001 to P = 0.05) for all methods. For all scenarios of
      enamel reduction, the actual amount of stripping was less than the predetermined
      and expected amount of stripping. The Kruskal-Wallis analysis showed no
      significant differences between the 3 methods. CONCLUSIONS: There were variations
      in the stripped amounts of enamel, and the stripping technique did not appear to
      be a significant predictor of the actual amount of enamel reduction. In most
      cases, actual stripping was less than the intended amount of enamel reduction.

PMID- 23540635
TI  - Litigation and legislation. The patient has a big mouth.

PMID- 23540636
TI  - Statistical methods for the assessment of orthodontic materials.

PMID- 23540637
TI  - Dimensional changes of extended-pour alginate impression materials.
AB  - INTRODUCTION: Recently, manufacturers have marketed alginate impression
      materials, claiming dimensional stability for up to 100 hours to allow shipping
      to a dental laboratory for digital model fabrication. The purpose of this study
      was to evaluate the dimensional changes of these newer materials after storage at
      different temperatures and times. METHODS: Two extended-pour alginates (claiming
      100 hours of accuracy) (Kromopan; Lascod, Florence, Italy; and Triphasix;
      Parkell, Edgewood, NY), 2 traditional alginates (Jeltrate; Dentsply-Caulk, York,
      Pa; and Kromatica; Matech, Sylmar, Calif), and 1 vinyl polysiloxane (VP Mix;
      Henry Schein, Melville, NY) were used to impress a scored aluminum die. The
      distance between the score lines was measured on the impressions at 10 minutes,
      24 hours, and 100 hours after mix, and the percentages of dimensional change were
      calculated. Temperature effects were studied by storage at cold (-9 degrees C),
      room (22 degrees C), or hot (46 degrees C) temperatures for 8 hours. RESULTS: All
      alginates had statistically significant dimensional changes at 24 and 100 hours
      (0.69%-6.13%). VP Mix exhibited no statistically significant changes for any
      storage condition. The Kromopan (100 hour) and Kromatica (traditional) alginates
      were the most stable (0.85%-2.22% at 100 hours). Triphasix (100 hour) and
      Jeltrate (traditional) were the least stable (1.53%-4.73% at 100 hours). Cold
      temperature storage resulted in the most dimensional changes (1.96%-4.73% at 100
      hours). Room-temperature storage resulted in the least dimensional changes (0.97%
      1.53% at 100 hours). CONCLUSIONS: All alginate impression materials in the study
      had significant changes at 24 and 100 hours in all storage conditions tested.

PMID- 23540638
TI  - Tooth whitening in the orthodontic practice: a survey of orthodontists.
AB  - INTRODUCTION: The demand for tooth whitening has grown almost exponentially in
      the last 20 years, but there are no published reports regarding how bleaching is
      used in contemporary orthodontic practices in the United States. METHODS: A
      weighted sample of American Association of Orthodontists members (3601) was
      surveyed via electronic and paper questionnaires to quantitatively, by logistic
      regression, and qualitatively assess orthodontists' current practices regarding
      tooth-whitening procedures. RESULTS: Of the surveys, 1222 were completed, and
      1182 surveys were eligible for analysis. Nationwide, 88.8% of orthodontists had
      patients who requested tooth whitening, and 76.2% of orthodontists had recently
      recommended whitening procedures for some patients, typically less than 25% of
      their total patient population. Approximately a third (32.8%) of orthodontists
      provided whitening, and nearly two thirds (65.8%) referred whitening procedures
      to other dental professionals. The geographic region of the country had a
      statistically significant effect on the proportion of orthodontists who received
      whitening requests (P = 0.004), recommended whitening procedures (P <0.0006), and
      provided whitening services in their specialty practices (P <0.0001).
      CONCLUSIONS: Almost all orthodontists encounter patients who request whitening
      procedures, and most recommend whitening procedures for a small percentage of
      their patients. The proportion of orthodontists who refer such procedures to
      other providers is nearly double the proportion that provides them.

PMID- 23540639
TI  - Colonization of Streptococcus mutans on esthetic brackets: self-ligating vs
      conventional.
AB  - INTRODUCTION: Self-ligating orthodontic brackets rely on clips, rather than
      ligatures, to hold the archwire in place. It is unknown whether replacing
      ligatures with clips affects the adherence of Streptococcus mutans. The aim of
      this research was to evaluate whether self-ligating brackets have an advantage
      over conventional brackets as determined by the adherence of S mutans. METHODS:
      The sample consisted of 50 esthetic brackets, divided into 3 experimental groups
      and 2 control groups of 10 brackets each. Two experimental groups were active
      self-ligating brackets (QuicKlear; Forestadent, Pforzheim, Germany; and In
      Ovation C; Dentsply GAC, Bohemia, NY); the other was a passive self-ligating
      bracket (Damon 3; Ormco, Glendora, Calif). The 2 control groups were conventional
      brackets (Mystique; Dentsply GAC; and Clarity; 3M Unitek, Monrovia, Calif). The
      brackets were randomly bonded to the canines, first and second premolars, and
      first and second molars in the mandibular left hemiarch of 10 male participants.
      Biofilm was collected from the tooth surfaces before bonding and from the
      brackets on day 21 and placed in Petri dishes containing Mitis salivarius agar.
      The brackets were removed on day 28 and examined by using scanning electron
      microscopy. Statistical analysis, analysis of variance, and the Tukey correction
      with a P value of 0.05 were used. RESULTS: The greatest numbers of colonies were
      found in an active self-ligating bracket group (In-Ovation C), and the fewest
      colonies were in a conventional bracket group (Clarity). The largest colonies
      formed on active self-ligating brackets. In the slot, the greatest formation was
      in a control group (Mystique). CONCLUSIONS: Self-ligating esthetic brackets do
      not promote greater or lesser S mutans colonization when compared with
      conventional brackets. Differences were found to be related to the material
      composition of the bracket.

PMID- 23540640
TI  - Evaluation of 3 commercially available materials for resolution of white spot
      lesions.
AB  - INTRODUCTION: White spot lesions are often seen on the teeth after orthodontic
      treatment, resulting in unpleasant esthetics. The aim of this in-vitro study was
      to compare subjectively and objectively the esthetic outcomes of white spot
      lesions treated with 3 commercially available products that have been reported to
      have a positive effect on the remineralization of enamel. METHODS: Forty
      extracted premolars were randomly allocated into 1 of 4 groups (n = 10). The
      teeth were exposed to a demineralization solution at 37 degrees C for 14 days to
      produce white spot lesions that were about 100 MUm deep. Each group was then
      randomly assigned to receive either control treatment with artificial saliva or
      treatment with 1 of the 3 commercially available products: Restore toothpaste
      (Dr. Collins Inc, Orange County, Calif), which contains NovaMin (Dr. Collins
      Inc); Prevident 5000 (Colgate, New York, NY); and MI Paste Plus (GC America,
      Alsip, Ill). All groups were evaluated 5 times at 6 time points during the study.
      RESULTS: The subjective and objective results were mixed within groups and
      between groups for the products tested. CONCLUSIONS: We found no conclusive
      evidence that any of these 3 materials produced more favorable esthetic white
      spot lesion remineralization results.

PMID- 23540641
TI  - Cross-section dimensions and mechanical properties of esthetic orthodontic coated
      archwires.
AB  - INTRODUCTION: There has been continuing interest in the development and use of
      esthetic and effective orthodontic archwires. The aims of this study were to
      evaluate the inner alloy core dimensions of 4 brands of as-received esthetic
      coated wires and their mechanical properties before and after 21 days of oral
      exposure, compared with conventional stainless steel and nickel titanium wires.
      METHODS: Four groups (Ortho Organizers, Carlsbad, Calif; TP Orthodontics,
      LaPorte, Ind; Orthometric, Beijing, China; and Trianeiro, Rio Claro, Sao Paulo,
      Brazil) of orthodontic archwires were tested. Five properties were evaluated:
      inner wire dimensions, modulus of elasticity, modulus of resilience, maximum
      deflection force, and load deflection curve characteristics. Images of the
      transverse sections from the specimens were made with a stereoscope. The inner
      alloy core dimensions of each wire were measured by using Image Pro Plus software
      (version 4.5; Media Cybernetics, Silver Spring, Md). All specimens were tested in
      a universal testing machine in a 3-point bending test. RESULTS: Coated wires of
      the Ortho Organizers and Trianeiro groups showed greater reductions in their
      inner alloy core dimensions and produced lower loading and unloading forces and
      lower modulus of elasticity, modulus of resilience, and maximum deflection force
      values than did their control wires. Inner alloy core dimensions and the
      mechanical behavior of coated wires practically did not differ from the control
      wires in the TP Orthodontics and Orthometric groups. CONCLUSIONS: The reduction
      on the inner alloy core dimensions to compensate for the coating thickness seems
      to be the variable responsible for greater changes in the mechanical properties
      of esthetic coated wires.

PMID- 23540642
TI  - Curing lights for orthodontic bonding: a systematic review and meta-analysis.
AB  - INTRODUCTION: Light cure of resin-based adhesives is the mainstay of orthodontic
      bonding. In recent years, alternatives to conventional halogen lights offering
      reduced curing time and the potential for lower attachment failure rates have
      emerged. The relative merits of curing lights in current use, including halogen
      based lamps, light-emitting diodes (LEDs), and plasma arc lights, have not been
      analyzed systematically. In this study, we reviewed randomized controlled trials
      and controlled clinical trials to assess the risks of attachment failure and
      bonding time in orthodontic patients in whom brackets were cured with halogen
      lights, LEDs, or plasma arc systems. METHODS: Multiple electronic database
      searches were undertaken, including MEDLINE, EMBASE, and the Cochrane Oral Health
      Group's Trials Register, CENTRAL. Language restrictions were not applied.
      Unpublished literature was searched on ClinicalTrials.gov, the National Research
      Register, Pro-Quest Dissertation Abstracts, and Thesis database. Search terms
      included randomized controlled trial, controlled clinical trial, random
      allocation, double blind method, single blind method, orthodontics, LED, halogen,
      bond, and bracket. Authors of primary studies were contacted as required, and
      reference lists of the included studies were screened. RESULTS: Randomized
      controlled trials and clinical controlled trials directly comparing conventional
      halogen lights, LEDs, or plasma arc systems involving patients with full arch,
      fixed, or bonded orthodontic appliances (not banded) with follow-up periods of a
      minimum of 6 months were included. Using predefined forms, 2 authors undertook
      independent extraction of articles; disagreements were resolved by discussion.
      The assessment of the risk of bias of the randomized controlled trials was based
      on the Cochrane Risk of Bias tool. Ten studies met the inclusion criteria; 2 were
      excluded because of high risk of bias. In the comparison of bond failure risk
      with halogen lights and plasma arc lights, 1851 brackets were included in both
      groups. Little statistical heterogeneity was observed in this analysis (I(2) =
      4.8%; P = 0.379). There was no statistical difference in bond failure risk
      between the groups (OR, 0.92; 95% CI, 0.68-1.23; prediction intervals, 0.54,
      1.56). Similarly, no statistical difference in bond failure risk was observed in
      the meta-analysis comparing halogen lights and LEDs (OR, 0.96; 95% CI, 0.64-1.44;
      prediction intervals, 0.07, 13.32). The pooled estimates from both comparisons
      were OR, 0.93; 95% CI, 0.74-1.17; and prediction intervals, 0.69, 1.17.
      CONCLUSIONS: There is no evidence to support the use of 1 light cure type over
      another based on risk of attachment failure.

PMID- 23540643
TI  - Photothermal colloid antibodies for shape-selective recognition and killing of
      microorganisms.
AB  - We have developed a class of selective antimicrobial agents based on the
      recognition of the shape and size of the bacterial cells. These agents are
      anisotropic colloid particles fabricated as negative replicas of the target cells
      which involve templating of the cells with shells of inert material followed by
      their fragmentation. The cell shape recognition by such shell fragments is due to
      the increased area of surface contact between the cells and their matching shell
      fragments which resembles antibody-antigen interaction. We produced such "colloid
      antibodies" with photothermal mechanism for shape-selective killing of matching
      cells. This was achieved by the subsequent deposition of (i) gold nanoparticles
      (AuNPs) and (ii) silica shell over yeast cells, which were chosen as model
      pathogens. We demonstrated that fragments of these composite AuNP/silica shells
      act as "colloid antibodies" and can bind to yeast cells of the same shape and
      size and deliver AuNPs directly onto their surface. We showed that after laser
      irradiation, the localized heating around the AuNPs kills the microbial cells of
      matching shape. We confirmed the cell shape-specific killing by photothermal
      colloid antibodies in a mixture of two bacterial cultures of different cell shape
      and size. This approach opens a number of avenues for building powerful selective
      biocides based on combinations of colloid antibodies and cell-killing strategies
      which can be applied in new antibacterial therapies.

PMID- 23540644
TI  - Small-molecule inhibitors of cathepsin L incorporating functionalized ring-fused
      molecular frameworks.
AB  - Cathepsin L is a cysteine protease that is upregulated in a variety of malignant
      tumors and plays a significant role in cancer cell invasion and migration. It is
      an attractive target for the development of small-molecule inhibitors, which may
      prove beneficial as treatment agents to limit or arrest cancer metastasis. We
      have previously identified a structurally diverse series of thiosemicarbazone
      based inhibitors that incorporate the benzophenone and thiochromanone molecular
      scaffolds. Herein we report an important extension of this work designed to
      explore fused aryl-alkyl ring molecular systems that feature nitrogen atom
      incorporation (dihydroquinoline-based) and carbon atom exclusivity
      (tetrahydronaphthalene-based). In addition, analogues that contain oxygen
      (chromanone-based), sulfur (thiochroman-based), sulfoxide, and sulfone
      functionalization have been prepared in order to further investigate the
      structure-activity relationship aspects associated with these compounds and their
      ability to inhibit cathepsins L and B. From this small-library of 30 compounds,
      five were found to be strongly inhibitory (IC50 <500 nM) against cathepsin L with
      the most active compound (7-bromodihydroquinoline thiosemicarbazone 48)
      demonstrating an IC50=164 nM. All of the compounds evaluated were inactive (IC50
      >10,000 nM) as inhibitors of cathepsin B, thus establishing a high degree (>20
      fold) of selectivity (cathepsin L vs. cathepsin B) for the most active cathepsin
      L inhibitors in this series.

PMID- 23540645
TI  - Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase
      beta isoform.
AB  - A series of suitable five-membered heterocyclic alternatives to thiophenes within
      a thienobenzoxepin class of PI3-kinase (PI3K) inhibitors was discovered. Specific
      thiazolobenzoxepin 8-substitution was identified that increased selectivity over
      PI3Kbeta. PI3Kbeta-sparing compound 27 (PI3Kbeta Ki,app/PI3Kalpha Ki,app=57)
      demonstrated dose-dependent knockdown of pAKT, pPRAS40 and pS6RP in vivo as well
      as differential effects in an in vitro proliferation cell line screen compared to
      pan PI3K inhibitor GDC-0941. A new structure-based hypothesis for reducing
      inhibition of the PI3K beta isoform while maintaining activity against alpha,
      delta and gamma isoforms is presented.

PMID- 23540647
TI  - Synthesis and antioxidant properties of substituted 2-phenyl-1H-indoles.
AB  - In this study, we report the design, synthesis and antioxidant activity of a
      series of substituted 2-(4-aminophenyl)-1H-indoles and 2-(methoxyphenyl)-1H
      indoles. The new compounds are structurally related to the known indole-based
      antioxidant lead compound melatonin (MLT), and the antitumour 2-(4
      aminophenyl)benzothiazole and 2-(3,4-dimethoxyphenyl)benzothiazole series.
      Efficient access to the target 2-phenylindoles was achieved via Fischer indole
      synthesis between substituted phenylhydrazines and acetophenones. 2-(4
      Aminophenyl)indoles (such as the 6-fluoro analogue 3b) in particular showed
      potent antioxidant activity in the DPPH and superoxide radical scavenging assays
      (80% and 81% inhibition at 1mM concentration of 3b, respectively), at a level
      comparable with the reference standard MLT (98% and 75% at 1 mM).

PMID- 23540646
TI  - Design, synthesis and biological activity of multifunctional alpha,beta
      unsaturated carbonyl scaffolds for Alzheimer's disease.
AB  - A series of compounds containing an alpha,beta-unsaturated carbonyl moiety, such
      as chalcones and coumarins were designed, synthesized and tested in a variety of
      assays to assess their potential as anti-Alzheimer's disease (AD) agents. The
      investigations included the inhibition of cholinesterases (AChE, BuChE), the
      inhibition of amyloid beta (Abeta) self-assembly and the disassembly of preformed
      Abeta oligomers. Several compounds showed excellent potential as multifunctional
      compounds for AD. Docking studies for 16 that performed well in all the assays
      gave a clear interpretation of various interactions in the gorge of AChE. Based
      on the results, the long-chain coumarin scaffold appears to be a promising
      structural template for further AD drug development.

PMID- 23540648
TI  - Strategic use of conformational bias and structure based design to identify
      potent JAK3 inhibitors with improved selectivity against the JAK family and the
      kinome.
AB  - Using a structure based design approach we have identified a series of indazole
      substituted pyrrolopyrazines, which are potent inhibitors of JAK3. Intramolecular
      electronic repulsion was used as a strategy to induce a strong conformational
      bias within the ligand. Compounds bearing this conformation participated in a
      favorable hydrophobic interaction with a cysteine residue in the JAK3 binding
      pocket, which imparted high selectivity versus the kinome and improved
      selectivity within the JAK family.

PMID- 23540649
TI  - Pattern recognition receptor function in neutrophils.
AB  - Previously, neutrophils were largely ignored in the pattern recognition receptor
      (PRR) signaling field. However, interest in neutrophil biology has been
      revitalized by emerging roles for neutrophils in promoting protective and
      pathogenic T helper (Th)17-driven immune responses and in orchestrating innate
      and adaptive immunity via cytokine/chemokine production. Although it was
      originally assumed that neutrophils are transcriptionally inert and their short
      lifespan limits their ability to respond to PRR agonists, the past 5 years has
      seen tremendous advances in neutrophil PRR signaling that have shifted this
      paradigm. Here, we review recent findings that demonstrate that neutrophils
      express a broad repertoire of PRRs, respond dynamically to their stimulation
      during infection and inflammation, and that neutrophil PRRs are key regulators of
      in vivo host immune responses. 

PMID- 23540652
TI  - Influence of age and renal function on high-sensitivity cardiac troponin T
      diagnostic accuracy for the diagnosis of acute myocardial infarction.
AB  - Concerns have been raised about the performance of highly sensitive cardiac
      troponin assays to accurately detect acute myocardial infarction (AMI),
      particularly in non-ST segment elevation (NSTEMI), in elderly patients, and in
      patients with renal failure. We evaluated whether increased age and low estimated
      glomerular filtration rate (eGFR) alter diagnostic performance of high
      sensitivity cardiac troponin T (HScTnT). In a prospective multicentric study,
      HScTnT levels were measured blindly at presentation in patients with acute chest
      pain. Three hundred and sixty-seven patients were enrolled, including 84 patients
      >=70 years. Final diagnosis was AMI for 57 patients (16%) and NSTEMI for 43
      patients (12%). NSTEMI was more frequent in elderly patients (p = 0.008).
      Sensitivity and specificity of HScTnT >14 ng/L at admission for AMI were 96% and
      51% in patients >=70 years versus 91% (NS) and 88% (p <0.0001) in younger
      patients; the same observations were done for the diagnosis of NSTEMI. Given an
      HScTnT >53.5 ng/L for the diagnosis of AMI and NSTEMI, respective sensitivities
      were 87% and 84% and respective specificities were 87% and 87% in elderly
      patients. Using a cutoff at 35.8 ng/L (for AMI) or 43.2 ng/L (for NSTEMI),
      sensitivities were 94% and 92%, and specificities were 86% and 88% in patients
      with low eGFR. Older age, but not low eGFR, was an independent predictive factor
      of an elevated HScTnT at admission (odds ratio 2.2 [1.2-3.9], p = 0.007). In
      conclusion, adapted thresholds of HScTnT are required for an accurate diagnosis
      of AMI/NSTEMI in patients aged >=70 and in those with low eGFR.

PMID- 23540650
TI  - Antigen cross-presentation by dendritic cell subsets: one general or all
      sergeants?
AB  - Antigen cross-presentation describes the process through which dendritic cells
      (DCs) acquire exogenous antigens for presentation on MHC class I molecules. The
      ability to cross-present has been thought of as a feature of specialized DC
      subsets. Emerging data, however, suggest that the cross-presenting ability of
      each DC subset is tuned by and dependent on several factors, such as DC location
      and activation status, and the type of antigen and inflammatory signals. Thus, we
      argue that capacity of cross-presentation is not an exclusive trait of one or
      several distinct DC subtypes, but rather a common feature of the DC family in
      both mice and humans. Understanding DC subset activation and antigen-presentation
      pathways might yield improved tools and targets to exploit the unique cross
      presenting capacity of DCs in immunotherapy. 

PMID- 23540653
TI  - Usefulness of step counts to predict mortality in Japanese patients with heart
      failure.
AB  - The purpose of this study was to determine both an association between mortality
      and physical activity (PA) objectively measured by accelerometer and cutoff
      values for PA in Japanese outpatients with heart failure (HF). This prospective
      observational study comprised 170 HF outpatients (mean age, 65.2 years; 77% men).
      Peak oxygen uptake (VO2) and the relation between ventilation and carbon dioxide
      production (VE/VCO2 slope) as indices of exercise capacity were measured during
      cardiopulmonary exercise testing with a cycle ergometer. PA was assessed by
      accelerometer-measured average step count (steps) per day for 1 week. Study
      endpoint was cardiovascular-related death. Over an average follow-up of 1,377.1
      (median, 1,335) days, 31 cardiovascular-related deaths occurred. Patients were
      then divided into survivor (n = 139) and nonsurvivor (n = 31) groups. Brain
      natriuretic peptide level was significantly different between groups. Peak VO2
      and steps were also significantly lower and VE/VCO2 slope higher in the
      nonsurvivors versus survivors. Univariate Cox proportional hazards analysis
      showed brain natriuretic peptide, peak VO2, VE/VCO2 slope, and steps to be
      significant prognostic indicators of survival. Multivariate analysis showed PA of
      <=4,889.4 steps/day to be a strong and independent predictor of prognosis (hazard
      ratio: 2.28, 95% confidence interval: 1.31-6.30; p = 0.008). Kaplan-Meier curves
      after log-rank test showed significant prognostic difference between PA of
      <=4,889.4 and >4,889.4 steps/day in the 2 groups (log-rank: 12.19; p = 0.0005).
      In conclusion, step count as objectively measured by accelerometer may be a
      prognostic indicator of mortality in Japanese outpatients with HF.

PMID- 23540654
TI  - Coronary superficial and spotty calcium deposits in culprit coronary lesions of
      acute coronary syndrome as determined by optical coherence tomography.
AB  - The characteristics of coronary artery calcium responsible for vulnerable plaque
      remain incompletely elucidated. We used optical coherence tomography to
      investigate the characteristics of coronary calcium in acute myocardial
      infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris
      (SAP). We evaluated calcium deposits in the culprit lesions (30-mm segment) using
      optical coherence tomography in 187 patients with AMI (n = 44), UAP (n = 73), or
      SAP (n = 70). The arc, area, and length of calcium were significantly smaller in
      those with AMI and UAP than in those with SAP (p <0.001). The number of spotty
      calcium deposits (with an arc of <90 degrees ) per patient was significantly
      larger in the AMI and UAP groups than in the SAP group (p <0.001). The number of
      large calcium deposits (with an arc of >90 degrees ) per patient was
      significantly lower in the AMI and UAP groups than in the SAP group (p <0.001).
      The minimum distance between the inner edge of the calcium and the luminal
      surface was significantly shorter in the AMI and UAP groups than in the SAP group
      (p <0.001). Plaque rupture frequency correlated positively with the number of
      spotty calcium deposits (r = 0.479, p <0.001) and inversely with the number of
      large calcium deposits (r = -0.219, p = 0.003). In conclusion, calcium was very
      spotty and more superficial in the culprit lesions of AMI and UAP. These
      characteristics of calcium might play an important role in the pathogenesis of
      plaque vulnerability.

PMID- 23540656
TI  - Stability of aortic annulus enlargement during aortic valve replacement using a
      bovine pericardial patch: an 18-year clinical, echocardiographic, and angio
      computed tomographic follow-up.
AB  - OBJECTIVE: Enlargement of the aortic annulus may be required during aortic valve
      replacement to avoid patient-prosthesis mismatch. We reviewed patients with
      enlargement of the aortic annulus with the aim of assessing the stability of the
      procedure by means of echocardiographic and angio-computed tomography studies.
      METHODS: A series of 53 consecutive patients underwent aortic valve replacement
      and enlargement of the aortic annulus from 1994 to 2012. The mean age was 68 +/-
      11 years (range, 29-84 years), and 85% (45 patients) were female. The predominant
      valvular lesion was aortic stenosis. The mean logistic European System for
      Cardiac Operative Risk Evaluation was 11.2 +/- 13.0. Enlargement of the aortic
      annulus was performed by extending the aortotomy incision to separate the
      commissure between the left and noncoronary sinuses into the anterior mitral
      leaflet and closing the resulting defect with an adequately tailored patch of
      bovine pericardium. RESULTS: Hospital mortality was 2%, with 20 late deaths
      mostly due to noncardiac causes. At a maximum follow-up of 18 years (mean, 8.9 +/
      5.0 years), actuarial survival is 37% +/- 9%. No cases of severe patient
      prosthesis mismatch were observed, and only 2 patients had moderate patient
      prosthesis mismatch. At discharge, the mean aortic root diameter was 30.0 +/- 2.3
      mm and the mean diameter at the sinotubular junction was 31.5 +/- 5.0 mm. At
      follow-up, the mean aortic root diameter was 31.0 +/- 3.4 mm and the mean
      diameter at the sinotubular junction was 31.7 +/- 4.5 mm (P = not significant)
      with no cases of late aneurysm formation on angio-computed tomography.
      CONCLUSIONS: Enlargement of the aortic annulus is a safe and effective procedure
      and should be indicated in patients with a small aortic annulus; particularly, it
      should be considered to prevent patient-prosthesis mismatch and its potential
      deleterious long-term effects.

PMID- 23540655
TI  - Rodent brain slice model for the study of white matter injury.
AB  - OBJECTIVE: Cerebral white matter (WM) injury is common after cardiac surgery in
      neonates and young infants who have brain immaturity and genetic abnormalities.
      To understand better the mechanisms associated with WM injury, we tested the
      adequacy of a novel ex vivo brain slice model, with a particular focus on how the
      maturational stage modulates the injury. METHODS: To replicate conditions of
      cardiopulmonary bypass, we transferred living brain slices to a closed chamber
      perfused by artificial cerebrospinal fluid under controlled temperature and
      oxygenation. Oxygen-glucose deprivation (OGD) simulated circulatory arrest. The
      effects of maturation were investigated in 7- and 21-day-old mice (P7, P21) that
      are equivalent in maturation stage to the human fetus and young adult. RESULTS:
      There were no morphologic changes in axons after 60 minutes of OGD at 15 degrees
      C in both P7 WM and P21 WM. Higher temperature and longer duration of OGD were
      associated with significantly greater WM axonal damage, suggesting that the model
      replicates the injury seen after hypothermic circulatory arrest. The axonal
      damage at P7 was significantly less than at P21, demonstrating that immature
      axons are more resistant than mature axons. Conversely, a significant increase in
      caspase3(+) oligodendrocytes in P7 mice was identified relative to P21,
      indicating that oligodendrocytes in immature WM are more vulnerable than
      oligodendrocytes in mature WM. CONCLUSIONS: Neuroprotective strategies for
      immature WM may need to focus on reducing oligodendrocyte injury. The brain slice
      model will be helpful in understanding the effects of cardiac surgery on the
      immature brain and the brain with genetic abnormalities.

PMID- 23540659
TI  - Endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis:
      testing the current guidelines.
AB  - BACKGROUND: Current guidelines include an algorithm for predicting
      choledocholithiasis. Presence of any very strong predictor or both strong
      predictors confers a high (>50%) probability of choledocholithiasis. Absence of
      predictors confers low risk (<10%) of choledocholithiasis. Other combinations
      have an intermediate risk of choledocholithiasis. AIM: Determine accuracy of the
      proposed algorithm in predicting choledocholithiasis. METHODS: Retrospective
      analysis of all endoscopic retrograde cholangiopancreatographies performed for
      suspected choledocholithiasis in 3 years in a Tertiary care hospital and a
      community hospital serviced by The University of Texas Health Science Center at
      Houston Division of Gastroenterology. Application of the guidelines, and
      comparing results to endoscopic retrograde cholangiopancreatography findings.
      RESULTS: A total of 1080 endoscopic retrograde cholangiopancreatographies were
      performed; 521 for choledocholithiasis. Most patients were Hispanic and female.
      Univariate analysis: presence of any very strong predictor and both strong
      predictors had an OR for choledocholithiasis of 3.30 and 2.36 respectively.
      Multivariate analysis: odds of choledocholithiasis with any very strong predictor
      was 2.87, and both strong predictors 3.24. Choledocholithiasis was present in
      71.5%, and 41% of patients with high, and intermediate risk respectively.
      CONCLUSION: This study confirms the utility of clinical predictors for the
      diagnosis of choledocholithiasis. All of the very strong predictors and one of
      the strong predictors increased the odds of choledocholithiasis. Patients with
      high risk for choledocholithiasis had a probability of 79% of
      choledocholithiasis. Sensitivity and specificity of current predictors are too
      low to obviate the possible need of non-invasive tests to confirm or exclude
      choledocholithiasis in all risk groups.

PMID- 23540662
TI  - Endovascular management of nonmalignant iliocaval venous lesions.
AB  - BACKGROUND: Iliocaval venous lesions produce a spectrum of symptoms ranging from
      mild swelling to venous ulcerations. In this study we examine the management and
      outcomes of these patients at our center. METHODS: In this study we performed a
      retrospective analysis of patients with symptomatic iliocaval venous stenoses,
      occlusions, or venous compression syndromes, who were treated with endovascular
      intervention during the period 2006-2010. RESULTS: Of the 36 patients evaluated,
      mean age was 43.0 years; prior deep venous thrombosis (DVT), pulmonary embolism
      (PE), and hypercoaguable states were present in 55.5%, 25.0%, and 44.4%,
      respectively. Patients were stratified by the presence (group I, n = 22) or
      absence (group II, n = 14) of underlying May-Thurner (MT) syndrome. In group I,
      11 patients had nonocclusive MT-related stenoses and 11 had acute DVT with
      underlying MT, causing pain/swelling (100%), venous claudication (66.7%), or CEAP
      class 3 (95%) or 6 (5%). Female preponderance was 2.1:1. Eighteen patients had
      successful intervention (angioplasty/stent with or without lysis), with clinical
      improvement in 94.4% and a decrease in CEAP score in 83.3%. All group II patients
      had chronic iliocaval occlusions causing: pain (100%); swelling (88.9%); venous
      claudication (44.4%); or CEAP class 3 (58%), 4 (25%), or 6 (8%). Recanalization
      was attempted in all patients and was successful in 71.4%. Successful
      recanalization was associated with clinical improvement in 88.9% and a decrease
      in CEAP score in 44.4%. Complications included 2 early reocclusions, 2 hematomas,
      and no cases of PE or death. Primary and secondary 1-year patency was 86% and
      100% overall (mean follow-up 9.6 months). Primary 1-year patency for groups I and
      II was 87.5% and 83.3%, respectively. CONCLUSIONS: Percutaneous intervention for
      chronic iliocaval venous lesions is associated with excellent 1-year patency
      rates and a significant reduction in symptoms and decrease in CEAP score.

PMID- 23540663
TI  - The chimney technique in endovascular aortic aneurysm repair: late ruptures after
      successful single renal chimney stent grafts.
AB  - BACKGROUND: The chimney graft technique has been proposed as an alternative
      endovascular treatment of juxtarenal aortic aneurysms, extending the landing zone
      and enabling successful exclusion of the aneurysm with standard endograft
      devices. METHODS: A prospective observational study assigning patients with
      juxtarenal aortic aneurysm treated with single renal chimney grafts in a tertiary
      vascular center in the United Kingdom was conducted. Primary outcome endpoints
      were defined as technical success, perioperative morbidity and mortality, and
      freedom from any type of endoleak, reintervention, and aneurysm-related death.
      RESULTS: Nine patients were enrolled. Successful aortic and chimney graft
      implantation was achieved in all patients. A proximal type I endoleak noticed on
      completion angiogram was treated with an aortic extension cuff. None of the
      patients died within 30 days of treatment. Two patients developed a type IA
      endoleak during follow-up, resulting in aneurysm rupture and death. Both patients
      had had uneventful chimney procedures, and no endoleak was evident on previous
      surveillance computed tomographic scans. All chimney grafts remained patent, and
      none of the patients developed renal impairment during the follow-up period.
      CONCLUSIONS: Proximal type I endoleak constitutes a weak point of chimney graft
      interventions. Increased vigilance in surveillance of such patients to prevent
      late aneurysm-related complications is required. Additional research to identify
      potential poor prognostic morphologic indicators is expected.

PMID- 23540664
TI  - Long-term quality of life of abdominal aortic aneurysm patients under
      surveillance or after operative treatment.
AB  - BACKGROUND: The objective of this study was to determine the long-term quality of
      life (QOL) in patients with an abdominal aortic aneurysm (AAA) undergoing
      surveillance or after operative treatment. METHODS: 249 patients with AAAs
      completed the WHO Quality of Life-BREF (WHOQOL-BREF) test and Short Form (36)
      Health Survey (SF-36) survey: 78 patients with small AAAs under surveillance, 26
      after ruptured AAAs (rAAAs), 47 after endovascular aneurysm repair (EVAR), and 98
      after elective open repair. The results were compared with WHOQOL-BREF and SF-36
      standard values from a matched German population using the Student's 2-tailed t
      test. RESULTS: Long-term results of the WHOQOL-BREF test showed that patients
      undergoing AAA surveillance had a significantly lower physical QOL (P = 0.04).
      Patients after EVAR or open repair rated their environmental QOL significantly
      higher than the age- and sex-matched general population (open repair: P = 0.006;
      EVAR: P < 0.001). Patients with rAAAs had the same QOL as the matched German
      population. Long-term results of the QOL SF-36 showed that patients undergoing
      AAA surveillance rated their QOL significantly lower in the subgroup of role
      physical (P = 0.02) and role-emotional (P = 0.003). Patients with rAAAs rated
      lower scores for role-physical (P = 0.02) and had more bodily pain (P = 0.02).
      Patients who underwent elective open repair had the same high QOL as the matched
      German population, whereas patients who underwent EVAR reported significant
      improvement in vitality (P = 0.002) and mental health (P = 0.03) compared with
      the matched German population. CONCLUSIONS: Based on measurements from 2
      independent QOL tests, the well-established operative treatment of AAAs provided
      patients with a QOL comparable to that of a matched German population. The
      electively treated AAA groups rated environmental QOL factors significantly
      higher than the control group. The impaired physical and emotional QOL of the AAA
      group under surveillance suggests that more intense patient education could be
      beneficial.

PMID- 23540665
TI  - A prospective randomized controlled clinical trial on clopidogrel combined with
      warfarin versus clopidogrel alone in the prevention of restenosis after
      endovascular treatment of the femoropopliteal artery.
AB  - BACKGROUND: We sought to compare the effects of clopidogrel combined with
      warfarin with clopidogrel alone in the prevention of restenosis after
      endovascular treatment (EVT) of the femoropopliteal artery. METHODS: Between June
      2008 and May 2009, 88 consecutive patients referred for EVT were randomly divided
      into a clopidogrel group (42 cases) and a clopidogrel combined with warfarin
      group (46 cases) before the procedure. Examinations including staging of
      peripheral arterial disease by Rutherford, ankle-brachial index, and color duplex
      ultrasonography were performed at baseline, 1 week, 3 months, 6 months, and 12
      months after procedure. At the same time, bleeding complications were observed.
      RESULTS: Fifty patients (63 limbs) were included after 12 months of follow-up, in
      which 25 patients (30 limbs) were from the clopidogrel group and 25 patients (33
      limbs) were from the combination group. At 3 months, the rates of restenosis on
      duplex ultrasonography were 17% in the clopidogrel group and 18% in the
      combination group (P = 1.0). At 6 months, the accumulated restenosis rates were
      37% and 36% (P = 0.98), respectively. At 12 months, the accumulated restenosis
      rates were 53% and 42% (P = 0.523), respectively. The rate of clinical bleeding
      events was 21% (6/29) in the combination group compared with 7% (2/27) in the
      clopidogrel group, and there was no statistical difference (P = 0.3).
      CONCLUSIONS: The combination of clopidogrel with warfarin was not more effective
      than clopidogrel alone in restenosis prevention for patients who underwent EVT.
      Instead, the combination of antiplatelet and anticoagulation therapy was inclined
      to increase the clinical bleeding events.

PMID- 23540661
TI  - Strategies for isolating and enriching cancer stem cells: well begun is half
      done.
AB  - Cancer stem cells (CSCs) constitute a subpopulation of cancer cells that have the
      potential for self-renewal, multipotent differentiation, and tumorigenicity.
      Studies on CSC biology and CSC-targeted therapies depend on CSC isolation and/or
      enrichment methodologies. Scientists have conducted extensive research in this
      field since John Dick's group successfully isolated CSCs based on the expression
      of the CD34 and CD38 surface markers. Progress in CSC research has been greatly
      facilitated by the enrichment and isolation of these cells. In this review, we
      summarize the current strategies used in our and other laboratories for CSC
      isolation and enrichment, including methods based on stem cell surface markers,
      intracellular enzyme activity, the concentration of reactive oxygen species, the
      mitochondrial membrane potential, promoter-driven fluorescent protein expression,
      autofluorescence, suspension/adherent culture, cell division, the identification
      of side population cells, resistance to cytotoxic compounds or hypoxia,
      invasiveness/adhesion, immunoselection, and physical property. Although many
      challenges remain to be overcome, it is reasonable to believe that more reliable,
      efficient, and convenient methods will be developed in the near future.

PMID- 23540666
TI  - Port-a-Cath complicated by infection or migration not removed by manual traction:
      usefulness of cardiac pacing leads extraction techniques.
AB  - BACKGROUND: Long-term use of Port-a-Caths (PACs) is related to device-related
      delayed complications. The aim of this study is to describe the high success rate
      and safety of cardiac pacing lead extraction techniques used for PACs complicated
      by infection or migration and not removed by manual traction. METHODS: During a
      13-year period (1997-2010), 19 consecutive PAC recipients (54.1+/-13 years, 11
      females) were referred to our hospital for PAC-related delayed complications and
      PACs not removable by manual traction (mean dwelling time 29.3+/-31 months).
      RESULTS: PAC implantation indications included gastrointestinal cancer (21%),
      breast cancer (15.7%), other malignant diseases (52.6%), and nonmalignant
      diseases (10.5%). PAC removal indications were breakdown due to subclavian crush
      (63.1%), breakdown due to unsuccessful previous removal attempt (21%), sepsis
      (10.5%), or malfunction (5.3%). Removal of fractured free-floating catheters (16)
      migrated toward the venous blood course was attempted by tool-guided traction in
      all cases except 1 in whom mechanical dilation was necessary. For the 3 intact
      ones (2 infected and one malfunctioning) we used tool-guided traction and single
      sheath mechanical dilation, depending on the vascular/cardiac-catheter setting.
      By using multiple venous approaches we removed 18 catheters completely and 1
      partially, achieving clinical success in all of the patients. The most commonly
      used venous approach was transfemoral (TFA; 73.6%), followed by the original
      venous entry site approach (VEA; 15.7%) and internal transjugular approach (ITA;
      10.5%). No major or minor complications were observed. CONCLUSIONS: In
      experienced centers, cardiac pacing lead extraction techniques may be considered
      as an additional, efficacious, safe option for extraction of otherwise
      nonremovable entrapped PACs before surgery.

PMID- 23540667
TI  - Effect of ethnicity and insurance type on the outcome of open thoracic aortic
      aneurysm repair.
AB  - OBJECTIVES: Mortality and complication rates for open thoracic aortic aneurysm
      repair have declined but remain high. The purpose of this study is to determine
      the influence of ethnicity and insurance type on procedure selection and outcome
      after open thoracic aneurysm repair. METHODS: Using the Nationwide Inpatient
      Sample database, ethnicity and insurance type were evaluated against the outcome
      variables of mortality and major complications associated with open thoracic
      aneurysm repair. The potential cofounders of age, gender, urgency of operation,
      and Deyo index of comorbidities were controlled. RESULTS: Between 2001 and 2005,
      a total of 10,557 patients were identified who underwent elective open thoracic
      aneurysm repair, with a significantly greater proportion of white patients (n =
      8524) compared with black patients (n = 819), Hispanic patients (n = 556), and
      patients categorized as other (n = 658). Most patients (67%) were male. Almost
      half (45%) of the procedures were performed for urgent/emergent indications.
      Overall mortality was 10.7% (n = 1126) and the rate of spinal cord ischemia was
      0.4% (n = 43). Univariate analysis revealed significant differences among race
      with regard to surgery type, income, hospital region, hospital bed size, and
      insurance type (P < 0.0001). Differences between insurance coverage were
      significant for gender, surgery type, income, hospital region, and race (P <
      0.0001). Bivariate analysis by race revealed differences for death (P < 0.0001),
      pneumonia (P < 0.0001), renal complications (P = 0.011), implant complications (P
      < 0.0001), temporary tracheostomy (P = 0.004), transfusion (P < 0.0001), and
      intubation (P < 0.0001). In terms of payer status, bivariate analysis by
      insurance coverage revealed differences in death (P < 0.0001), central nervous
      system complications (P = 0.008), pneumonia (P < 0.0001), myocardial infarction
      (P = 0.001), infection (P < 0.0001), renal complications (P < 0.0001),
      malnutrition (P < 0.0001), temporary tracheostomy (P < 0.0001), spinal cord
      ischemia (P = 0.001), transfusion (P < 0.0001), and intubation (P < 0.0001).
      CONCLUSIONS: A high percentage of open thoracic procedures (45%) are performed
      urgently or emergently in the United States, which is associated with increased
      morbidity and mortality. Both ethnicity and payer status were associated with
      significant differences in surgical outcomes, including mortality and frequency
      of complications after open thoracic aortic aneurysm repair.

PMID- 23540668
TI  - Endovascular treatment of abdominal aortic aneurysms involving iliac bifurcation:
      role of iliac branch graft device in prevention of buttock claudication.
AB  - BACKGROUND: The aim of this study was to describe our early experience with the
      use of iliac branch grafts (IBGs) in aortoiliac aneurysm repair at our
      institution and to evaluate the technical feasibility, short-term patency rate,
      and potential clinical benefits, with special focus on prevention of buttock
      claudication. METHODS: From March 2009 to November 2010, 9 consecutive patients
      (all men), mean age 71.1 years (range 62-80 years), underwent IBG implantation at
      our institution. Indications were abdominal aortic aneurysm (AAA) with common
      iliac artery (CIA) involvement (n = 7), bilateral CIA aneurysm (n = 1), and AAA
      with bilateral CIA and unilateral IIA involvement (n = 1). Postoperative
      endoleaks and patency rate were determined with computed tomography (CT) within 1
      month of implantation and 1 year thereafter, with concurrent clinical evaluation
      for pelvic ischemia. Mean follow-up period was 14.7 (range 9-29) months. RESULTS:
      Technical success rate, as defined by successful implantation of the iliac branch
      graft (IBG) with no intraprocedural type I or type III endoleak, was 100%. The
      mean hospitalization duration was 4 days (range 3-6 days), with 0% mortality at
      30 days. There were 3 cases of type II endoleak detected perioperatively, which
      were treated conservatively. Two endoleaks sealed spontaneously on the 1-month CT
      scan and 1 persists without aneurysm sac expansion. All stent-implanted aortic
      and iliac aneurysms remained stable in size during follow-up, with no aneurysm
      rupture or death recorded. All stent-implanted iliac branches remained patent on
      follow-up and all patients were asymptomatic. CONCLUSIONS: Iliac branch graft
      placement is a feasible technique with excellent short-term results in the
      treatment of abdominal aortic aneurysms involving the iliac bifurcation. This
      technique can efficiently prevent buttock claudication.

PMID- 23540669
TI  - Stent graft repair of paraanastomotic aneurysms after open descending thoracic
      and thoracoabdominal aortic aneurysm repair.
AB  - BACKGROUND: After open thoracic and thoracoabdominal aortic aneurysm repair,
      anastomotic aneurysms can form at or near the suture lines of the graft.
      Endovascular repair is an alternative to complicated reoperative open surgery. We
      report on our experience with endovascular treatment of these lesions. METHODS: A
      prospectively maintained database of endovascular thoracic aortic aneurysm
      repairs (TEVARs) performed at Mount Sinai Medical Center was reviewed and the
      initial procedures, comorbidities, clinical presentation, aneurysm
      characteristics, type of endograft, adjunctive procedures, and follow-up were
      analyzed. RESULTS: Of the 135 TEVAR procedures performed between June 2001 and
      December 2008, 9 patients had anastomotic aneurysms after a previous open repair.
      The mean age was 66.7 (range 41-89) years, 67% of whom were male. Of these 9
      patients, 5 had a descending thoracic repair, 3 had a type IV repair, and 1 had a
      type II thoracoabdominal repair. Aneurysm formation occurred in the following
      regions: proximal anastomosis (n = 2); intercostal patch (n = 1); distal
      anastomosis (n = 3); visceral patch (n = 2); and midgraft (n = 1). The initial
      technical success rate was 100%, with 8 patients receiving a thoracic tube graft
      and 1 a modular bifurcated device. Two patients required an adjunctive carotid
      subclavian bypass and 2 required extraanatomic revascularization of the visceral
      arteries. Mean follow-up was 16.5 months. There was 1 perioperative death
      secondary to a postoperative myocardial infarction. Three patients developed an
      endoleak with 1 requiring an intervention. One patient required an open
      thoracoabdominal repair at 3 months for a penetrating ulcer at the visceral
      segment and another died from a ruptured thoracic aneurysm proximal to the stent
      graft at 72 months. Two more died during the follow-up period of non-aneurysm
      related causes. Five patients had paraanastomotic shrinkage or no change and 1
      had an increase in size, and 3 had no follow-up imaging. CONCLUSIONS: Stent graft
      repair of paraanastomotic aneurysms after open descending thoracic and
      thoracoabdomninal repair is a reasonable option when patients have suitable
      anatomy. These patients, however, require close follow-up for the development of
      aneurysmal degeneration adjacent to the stent graft repair.

PMID- 23540670
TI  - Magnetic resonance detected carotid plaque hemorrhage is associated with
      inflammatory features in symptomatic carotid plaques.
AB  - BACKGROUND: Both magnetic resonance detected carotid plaque hemorrhage (MRI
      PH(+)) and features of inflammation are associated with increased risk of
      cerebrovascular events in patients with carotid stenosis. To further assess the
      potential of MRI PH as a biomarker for complicated carotid plaque, its
      relationship with inflammation needs to be assessed. In this study we assess
      whether MRI PH(+) carotid plaques are associated with inflammatory infiltration.
      METHODS: Thirty-five consecutive patients with symptomatic, high-grade carotid
      stenosis scheduled for carotid endarterectomy had preoperative MRI. The carotid
      plaques removed at operation were assessed for inflammatory features and compared
      with MRI findings. RESULTS: Twenty-one (60%) carotid arteries were MRI PH(+) and
      14 (40%) were MRI PH(-). The MRI PH(+) plaques were associated with histologic
      evidence of plaque hemorrhage, high lipid proportion, and low fibrous content.
      They also had higher levels of macrophage and lymphoid cells compared with MRI
      PH(-) plaques (P < 0.05, by chi2 test) and were more likely to be AHA VI (P <
      0.005, chi2 test). MRI PH(+) plaques were also more likely to be graded as
      unstable based on morphology and cellular composition. CONCLUSIONS: These
      findings demonstrate an association between MRI PH and signs of active plaque
      disease. The relationship between inflammatory activity and plaque instability
      may thus explain the increased risk associated with MRI PH(+) plaques and
      increased risk of symptoms.

PMID- 23540671
TI  - Does Palmaz XL stent deployment for type 1 endoleak during elective or emergency
      endovascular aneurysm repair predict poor outcome? A multivariate analysis of
      1470 patients.
AB  - BACKGROUND: Endovascular aneurysm repair (EVAR) is now the standard of care for
      elective infrarenal and ruptured abdominal aortic aneurysms (AAAs). Difficult
      proximal necks often require adjuvant measures to seal type 1 endoleaks. We
      believed this was a predictor of increased 30-day morbidity and mortality and
      reduced long-term survival. METHODS: We reviewed outcomes for all patients
      entered into our database between 2003 and 2010 who had EVAR for elective or
      ruptured AAAs. Patient demographics and operative indications were recorded.
      Operative procedures, including adjuvant procedures, such as Palmaz XL stent
      deployment, were documented. All postoperative deaths and morbidity were
      recorded. Long-term survival was calculated using life table analysis.
      Multivariate analysis was performed to determine significant predictors of early
      mortality. RESULTS: Between 2003 and 2010, 1470 patients underwent EVAR for AAA
      (1378 [93.7%] elective; 92 [6.3%] ruptured or emergent). Elective EVAR patients
      required Palmaz stent placement in 146 of 1378 (10.6%) cases; in emergent cases,
      Palmaz stents were required in 16 of 92 (17.4%) cases. This was not significantly
      different (P=0.06). Thirty-day mortality for elective EVAR was 1.6% (22/1378)
      compared with 21.7% (20/92) for emergent repair (P<0.0001). Thirty-day mortality
      among the 146 elective patients undergoing Palmaz stenting was 3.4% compared with
      1.4% in the 1232 non-Palmaz stent elective EVAR patients (P=0.085). In emergency
      cases, the 30-day mortality for the 16 Palmaz patients was 25% compared to 21%
      for the 76 non-Palmaz stent patients (P=0.76). Among 30-day survivors, there were
      428 of 1356 (31.6%) endoleaks identified in the elective patient group and 36 of
      72 (50%) in the emergency group (P<0.005). Of the 146 elective patients requiring
      insertion of a Palmaz stent, 65 (44%) developed endoleaks, significantly more
      than the 370 of 1232 (30%) in non-Palmaz elective patients (P=0.0004). Among the
      emergency group, there were also significantly more endoleaks among the 30-day
      survivors who had a Palmaz stent deployed. In elective EVAR requiring Palmaz XL
      stents, 14% still had type 1 endoleaks at the end of their procedure; 13% still
      had type 1 endoleaks in the rupture EVAR Palmaz group. Multivariate analysis of
      all patients found that while female sex, AAA diameter, and estimated blood loss
      predicted 30-day mortality, deployment of a Palmaz stent did not. Long-term
      survival among Palmaz patients was not significantly different from non-Palmaz
      patients in the elective or emergent setting, although Palmaz patients required
      more secondary interventions. CONCLUSIONS: During EVAR, deployment of a Palmaz
      stent is more frequently required in patients with rupture, female sex, and
      larger sac size. However, Palmaz stent deployment itself is not an independent
      predictor of increased 30-day mortality in either the elective or emergency
      setting or of poorer long-term survival. However, they are associated with a
      greater number of postoperative endoleaks, especially type 1 endoleaks, and
      predict a greater need for secondary interventions.

PMID- 23540672
TI  - Oxytocin protects rat skeletal muscle against ischemia/reperfusion injury.
AB  - BACKGROUND: Oxytocin (OXY) is a well-known nonapeptide that functions in
      reproduction. It is also known as an antioxidant in several organs. However,
      little is about its role in the protection of tissue against ischemia/reperfusion
      injury in skeletal muscle. The aim of this study was to evaluate the protective
      and therapeutic antioxidant effect of oxytocin in skeletal muscle during
      ischemia/reperfusion (I/R) injury. METHODS: Rats were divided into 4 groups.
      Hindlimb ischemia was achieved by clamping the common femoral artery in 3 of the
      groups, but not a control group. OXY was injected before ischemia in the
      preoperative (preop) I/R + OXY group and after the onset of ischemia in the
      postoperative (postop) I/R + OXY group. Saline solution was injected in the I/R
      group. Limbs were rendered ischemic for 90 min. At the end of 90-min reperfusion
      period, skeletal muscle tissue samples were taken from the ischemic muscle for
      evaluation at light and transmission electron microscopic levels. Biochemical
      analysis was done for malonedialdehyde and glutathione levels. Caspase
      immunohistochemistry was applied for apoptosis. RESULTS: The light- and electron
      microscopic scores of the OXY-treated groups were significantly lower than in the
      I/R group. The degree of tissue damage was ameliorated in the OXY-treated groups.
      The number of apoptotic cells was decreased in the OXY-treated groups compared
      with the I/R group. In OXY-treated groups, the malonedialdehyde level was lower
      than in the I/R group. Glutathione levels were found to be increased in the OXY
      treated groups compared with the I/R group. CONCLUSIONS: Oxytocin has a
      protective effect against I/R injury in skeletal muscle and may reduce the
      incidence of compartment syndrome.

PMID- 23540673
TI  - Spinal cord early ischemic preconditioning activates the stabilized fraction of
      beta-catenin after thoracoabdominal aortic occlusion in pigs.
AB  - BACKGROUND: Paraplegia after thoracoabdominal aortic surgery is a devastating
      complication attributed to motor neurons loss and dysfunction, due to spinal cord
      ischemia. beta-Catenin is a protein that has been associated with cell survival
      and healing and many studies have correlated this protein with late ischemic
      preconditioning (IPC). Herein we investigate the potential contribution of beta
      catenin in an early IPC animal model, and its relationship with heat shock
      protein 70 (Hsp70), suggesting a possible role of this protein as a first window
      of protection. METHODS: A total of 42 pigs were used in an experimental
      thoracoabdominal aortic occlusion model. Twelve animals were used for neurologic
      evaluation and were randomly assigned to 2 groups (A and B). The remaining 30
      animals were used in experiments for biologic measurements and
      innunohistochemical studies, and were randomly assigned to 5 groups (1-5).
      Western blotting analysis and immunoprecipitations were performed to study the
      levels of beta-catenin and its binding relationship with Hsp70. The cellular
      distribution of beta-catenin at various time-points was investigated by
      immunohistochemical studies. RESULTS: According to neurologic evaluation, the
      animals in the IPC+ischemia group had significantly better neurologic scores
      compared with those in the ischemia group, indicating a protective role for IPC.
      The biologic measurements demonstrated a significant (P=0.03) increase in beta
      catenin levels and translocation of the protein in the nucleus at the end of
      ischemic preconditioning. CONCLUSIONS: Our results suggest a significant role of
      beta-catenin in early IPC protection of spinal cord after thoracoabdominal
      occlusion, as IPC seems to trigger the activation of the beta-catenin stabilized
      fraction and, thus, its survival pathway.

PMID- 23540674
TI  - Ulcer due to chronic venous disease: a sociodemographic study in northeastern
      Brazil.
AB  - BACKGROUND: Venous ulcers account for 70% of chronic leg ulcers and affect about
      2-7% of the population, causing much socioeconomic impact and reducing patients'
      quality of life. In this study we aimed to describe the clinical features of
      venous ulcers and sociodemographic characteristics of patients with ulcers due to
      chronic venous disease (CVD). METHODS: This cross-sectional, observational study
      was conducted at the Vascular Surgery Service, Universidade Federal de Sergipe,
      in northeastern Brazil. The study included a consecutive series of 154 patients
      with active venous ulcers (CEAP C6) in the lower limb due to CVD.
      Sociodemographic characteristics (age, gender, race, monthly income, education,
      occupation, and caregiver) and clinical data (affected limb, ulcer site,
      etiopathogenesis, recurrence, and time elapsed since the first episode of ulcer)
      were collected. A possible correlation of time elapsed since the first episode of
      ulcer and number of recurrences with primary or secondary etiology was analyzed
      by Mann-Whitney U-test. RESULTS: Of the 154 patients analyzed, 79% were female,
      94% were ethnically black or brown, 90% had a monthly income less than or equal
      to minimum wage, 47% were illiterate, 35% had not completed elementary school,
      50% had informal jobs, 19.5% were retired, and 18.2% received sick pay from the
      social security system. The mean age was 53.7 years. Both limbs were affected
      similarly, and venous ulcers were located predominantly on the medial aspect of
      the leg (84%). The median time elapsed since the first episode of ulcer was 36
      months, being significantly higher in patients with venous ulcers of secondary
      etiology (P < 0.0003). The prevalence of recurrence was also significantly higher
      in patients with venous ulcers of secondary etiology (P < 0.001). According to
      CEAP classification, 65% of ulcers were primary (Ep), 94.1% demonstrated reflux
      involving the superficial system (As), 92% had incompetent perforators (Ap), 35%
      demonstrated reflux involving the deep system (Ad), and all ulcers showed reflux
      without obstruction (Pr). CONCLUSIONS: Venous ulcers were more prevalent among
      low-income patients, especially chronic, recurrent ulcers of primary etiology.
      This finding highlights the need for improvements in patient care and surgical
      treatment in most cases aimed at ulcer healing and reduced recurrence. Better
      care would improve patients' quality of life and reduce social security
      expenditures.

PMID- 23540675
TI  - Treatment outcome in patients with acute superior mesenteric artery embolism.
AB  - PURPOSE: The goals of this study were to investigate the treatment outcomes of
      acute mesenteric ischemia caused by superior mesenteric artery (SMA) embolism and
      identify the posttreatment prognostic factors. METHODS: The clinical data of 32
      episodes of acute SMA embolism in 30 patients, including 2 recurrent cases,
      between April 2003 and March 2011 were retrospectively reviewed. RESULTS: Median
      patient age was 74 years (range, 39-89 years), and 50% were male. Conservative
      treatment, including bowel rest, nasogastric drainage, intravenous fluid therapy,
      parenteral nutritional support, and anticoagulation therapy, was undertaken in 5
      patients with no clinical evidence of bowel gangrene, including 1 with recurrent
      ischemia. No deaths occurred among patients treated conservatively. A total of 27
      patients were treated with open surgical repair (25 embolectomies and 2 bowel
      resections alone). Among 25 patients treated with embolectomy, 14 required bowel
      resection. Most bowel resections (94%, 15/16) were limited, with the remaining
      length of small bowel greater than 150 cm, which could not cause short bowel
      syndrome. In-hospital mortality of surgery was 30%. No variables were associated
      with mortality after surgical intervention, including, age, gender, presence of
      bowel gangrene, and symptom duration. The overall 1-, 3-, and 5-year survival
      rates after initial successful treatment were 96%, 73%, and 44%, respectively,
      regardless of treatment type. CONCLUSIONS: Prompt diagnosis and treatment before
      extensive irreversible gangrene is the mainstay in the treatment of SMA embolism.
      Limited bowel gangrene was not associated with mortality.

PMID- 23540676
TI  - Granulocyte colony-stimulating factor minimizes negative remodeling of
      decellularized small diameter vascular graft conduits but not medial
      degeneration.
AB  - BACKGROUND: Poor endothelialization and intimal hyperplasia are major causes of
      small diameter vascular conduit (SDVC) failure. The present study was aimed to
      investigate the influence of granulocyte colony-stimulating factor (G-CSF) on
      inhibiting adverse remodeling of decellularized SDVCs. METHODS: Sprague-Dawley
      rats implanted with allograft infra renal abdominal aortic conduits were divided
      into 2 groups according to whether they were treated with G-CSF (+G-CSF group;
      n=6) or without (Decell group; n=6). The conduits were harvested at 8 weeks after
      surgery and examined for intimal hyperplasia, collagen deposition, and -actin
      staining cells. The medial layer was also examined for signs of cellular
      repopulation and changes in the elastic fiber morphology. RESULTS: Intergroup
      comparison of the intimal composition showed relatively sparse collagen content
      and predominance of -actin-staining cells in the +G-CSF group. The medial layer
      in the 2 groups showed similar degrees of elastic fiber degeneration and wall
      thinning relative to the normal aortic wall. However, the enhanced staining for
      von Willebrand factor and CD31, along with transmission electron microscopy
      findings of superior cellular and ultrastructural preservation, suggested that
      the remodeling and endothelialization in the +G-CSF conduits were superior to
      those in the Decell conduits. CONCLUSIONS: This study suggests that G-CSF exerts
      a positive influence on inhibiting adverse vascular remodeling of decellularized
      vascular conduit implants. However, whether G-CSF administration may also
      effectuate an improved ability to preserve the medial structural integrity is
      unclear.

PMID- 23540677
TI  - Primary extracranial vertebral artery aneurysms.
AB  - BACKGROUND: Extracranial vertebral artery aneurysms are uncommon and are usually
      associated with trauma or dissection. Primary cervical vertebral aneurysms are
      even rarer and are not well described. The presentation and natural history are
      unknown and operative management can be difficult. Accessing aneurysms at the
      skull base can be difficult and, because the frail arteries are often afflicted
      with connective tissue abnormalities, direct repair can be particularly
      challenging. We describe the presentation and surgical management of patients
      with primary extracranial vertebral artery aneurysms. METHODS: In this study we
      performed a retrospective, multi-institutional review of patients with primary
      aneurysms within the extracranial vertebral artery. RESULTS: Between January 2000
      and January 2011, 7 patients, aged 12-56 years, were noted to have 9 primary
      extracranial vertebral artery aneurysms. All had underlying connective tissue or
      another hereditary disorder, including Ehler-Danlos syndrome (n=3), Marfan's
      disease (n=2), neurofibromatosis (n=1), and an unspecified connective tissue
      abnormality (n=1). Eight of 9 aneurysms were managed operatively, including an
      attempted bypass that ultimately required vertebral ligation; the contralateral
      aneurysm on this patient has not been treated. Open interventions included
      vertebral bypass with vein, external carotid autograft, and vertebral
      transposition to the internal carotid artery. Special techniques were used for
      handling the anastomoses in patients with Ehler-Danlos syndrome. Although
      endovascular exclusion was not performed in isolation, 2 hybrid procedures were
      performed. There were no instances of perioperative stroke or death. CONCLUSIONS:
      Primary extracranial vertebral artery aneurysms are rare and occur in patients
      with hereditary disorders. Operative intervention is warranted in symptomatic
      patients. Exclusion and reconstruction may be performed with open and hybrid
      techniques with low morbidity and mortality.

PMID- 23540679
TI  - Electrophilic fragment-based design of reversible covalent kinase inhibitors.
AB  - Fragment-based ligand design and covalent targeting of noncatalytic cysteines
      have been employed to develop potent and selective kinase inhibitors. Here, we
      combine these approaches, starting with a panel of low-molecular-weight,
      heteroaryl-susbstituted cyanoacrylamides, which we have previously shown to form
      reversible covalent bonds with cysteine thiols. Using this strategy, we identify
      electrophilic fragments with sufficient ligand efficiency and selectivity to
      serve as starting points for the first reported inhibitors of the MSK1 C-terminal
      kinase domain. Guided by X-ray co-crystal structures, indazole fragment 1 was
      elaborated to afford 12 (RMM-46), a reversible covalent inhibitor that exhibits
      high ligand efficiency and selectivity for MSK/RSK-family kinases. At nanomolar
      concentrations, 12 blocked activation of cellular MSK and RSK, as well as
      downstream phosphorylation of the critical transcription factor, CREB.

PMID- 23540678
TI  - Chemistry and pharmacological studies of 3-alkoxy-2,5-disubstituted-pyridinyl
      compounds as novel selective alpha4beta2 nicotinic acetylcholine receptor ligands
      that reduce alcohol intake in rats.
AB  - Neuronal acetylcholine receptors mediate the addictive effects of nicotine and
      may also be involved in alcohol addiction. Varenicline, an approved smoking
      cessation medication, showed clear efficacy in reducing alcohol consumption in
      heavy-drinking smokers. More recently, sazetidine-A, which selectively
      desensitizes alpha4beta2 nicotinic receptors, was shown to significantly reduce
      alcohol intake in a rat model. To develop novel therapeutics for treating alcohol
      use disorder, we designed and synthesized novel sazetidine-A analogues containing
      a methyl group at the 2-position of the pyridine ring. In vitro pharmacological
      studies revealed that some of the novel compounds showed overall pharmacological
      property profiles similar to that of sazetidine-A but exhibited reduced agonist
      activity across all nicotinic receptor subtypes tested. In rat studies, compound
      (S)-9 significantly reduced alcohol uptake. More importantly, preliminary results
      from studies in a ferret model indicate that these novel nAChR ligands have an
      improved adverse side-effect profile in comparison with that of varenicline.

PMID- 23540680
TI  - The value of Doppler waveform analysis in predicting major lower extremity
      amputation among dialysis patients treated for diabetic foot ulcers.
AB  - AIMS: This study examined the predictors for lower extremity amputation (LEA) in
      patients with diabetic foot ulcers according to kidney function and, in the case
      of dialysis patients, specifically evaluated the vasculature with the ankle
      brachial index (ABI) and Doppler waveforms. METHODS: Among 658 diabetic patients
      admitted to the Diabetic Foot Care Center, 286 had an estimated glomerular
      filtration rate (eGFR)>= 60 ml/min per 1.73 m(2), 275 had an eGFR<60, and 97
      patients were under maintenance dialysis. All clinical variables were analyzed. A
      specialist retrospectively reviewed Doppler images of 78 of the patients in
      dialysis to evaluate peripheral arterial disease. RESULTS: Forty-two percent of
      patients with eGFR<60 presented with ABI<=0.90. For ABI values>1.40, the
      proportion of dialysis patients (31.3%) was greater than the proportion of
      patients with eGFR<60 (5.3%). Wagner wound classifications, reduced serum albumin
      levels, and low ABI values were the predictors for major LEA among patients in
      the non-dialysis groups. Nevertheless, these indicators were not predictive of
      the risk of amputation in diabetic patients on dialysis. The presence of poor
      monophasic waveforms in the dorsalis pedis artery or posterior tibial artery
      served as an independent predictor (odds ratio: 7.61; P=0.008) for major LEA
      among dialysis patients. The sensitivity and specificity were 88.0% and 59.6%,
      respectively. CONCLUSIONS: Poor monophasic Doppler waveforms of below-the-knee
      arteries, commonly found among dialysis patients in treatment for diabetic foot
      ulcers, can serve as an independent predictor for major LEA.

PMID- 23540681
TI  - The metabolic syndrome and CVD outcomes for a central Australian cohort.
AB  - We investigated if the metabolic syndrome (MetS) and its component risk factors
      predict cardiovascular disease (CVD) for Aboriginal people from central
      Australia. WHO (HR 2.83), NCEP (1.80) and IDF (2.47) definitions of the MetS all
      had positive associations with CVD, however offered little above individual MetS
      components for hyperglycaemia.

PMID- 23540682
TI  - Fructose intake and cardiovascular risk factors in youth with type 1 diabetes:
      SEARCH for diabetes in youth study.
AB  - AIMS: High consumption of dietary fructose has been shown to contribute to
      dyslipidemia and elevated blood pressure in adults, but there are few data in
      youth, particularly those at greater risk of cardiovascular disease (CVD). The
      aim of this study was to examine the association between fructose intake and CVD
      risk factors in a diverse population of youth with type 1 diabetes (T1D).
      METHODS: This was a cross-sectional analysis of data from the SEARCH for Diabetes
      in Youth study, including 2085 youth ages 10-22 years with T1D, of which 22% were
      racial/ethnic minority and 50% were female. A semi-quantitative food frequency
      questionnaire was used to assess intake. RESULTS: Median daily fructose
      consumption was 7.9% of total calories. Fructose intake was positively associated
      with triglycerides (p<.01), but not with total cholesterol, LDL-cholesterol, HDL
      cholesterol, or blood pressure after adjustment for physical activity and socio
      demographic, clinical, and dietary covariates. An increase in fructose intake of
      22 g (equivalent to a 12 oz can of soda) was associated with 23% higher odds of
      borderline/high versus low triglycerides (p<.005). CONCLUSION: These data suggest
      that children with T1D should moderate their intake of fructose, particularly
      those with borderline or high triglycerides.

PMID- 23540683
TI  - Lactate increases hepatic secretion of VLDL-triglycerides in humans.
AB  - OBJECTIVE: The pathophysiology of hypertriglyceridemia is complex hampering
      effective therapeutic strategies. Increased central parasympathetic nerve
      activity was shown to inhibit hepatic triglyceride (TG) excretion via modulation
      of liver stearyl-CoA desaturase (SCD)-1 activity in rodents. We evaluated the
      impact of 7-h lactate clamping on VLDL-TG homeostasis in humans. METHODS: Eight
      normolipidemic, male subjects were subjected to a continuous infusion of l
      lactate (target concentration 3 mmol/L) or saline for 7 h in random order on two
      separate occasions. TG kinetics in very low density lipoproteins (VLDL1 and 2)
      were measured after a bolus injection of [1,1,2,3,3]-(2)H5-glycerol. Palmitic
      acid (16:0) and palmitoleic acid (16:1) in VLDL1 and VLDL2 were measured as a
      reflection of liver SCD1 activity. RESULTS: Plasma TG levels changed by 0.16 +/-
      0.09 mmol/L during lactate vs -0.15 +/- 0.08 mmol/L during saline (P < 0.05).
      VLDL1 16:1/16:0 ratio increased to 1.2 +/- 0.7 during lactate versus a decrease
      during saline by -1.5 +/- 0.6 (p = 0.01). During lactate VLDL1-TG excretion was
      higher compared to saline (1604 [827-2870] versus 1285 [505-2155] MUmol glycerol;
      p < 0.05), trending toward higher VLDL1-TG pool sizes during lactate (28%; p =
      0.07 versus saline). CONCLUSIONS: In normolipidemic men, 7-h l-lactate clamp
      increases, rather than decreases SCD1 activity and hepatic TG secretion leading
      to elevated plasma TG levels. These conflicting data between human and rodents on
      central regulation of hepatic TG excretion illustrate that experimental findings
      on the role of the central nervous system in lipid metabolism should be
      interpreted with caution.

PMID- 23540684
TI  - Switching on/off the chemisorption of thioctic-based self-assembled monolayers on
      gold by applying a moderate cathodic/anodic potential.
AB  - An in situ and real-time electrochemical method has been devised for
      quantitatively monitoring the self-assembly of a ferrocene-labeled cyclic
      disulfide derivative (i.e., a thioctic acid derivative) on a polycrystalline gold
      electrode under electrode polarization. Taking advantage of the high sensitivity,
      specificity, accuracy, and temporal resolution of this method, we were able to
      demonstrate an unexpectedly facilitated formation of the redox-active SAM when
      the electrode was held at a moderate cathodic potential (-0.4 V vs SCE in CH3CN),
      affording a saturated monolayer from only micromolar solutions in less than 10
      min, and a totally impeded SAM growth when the electrode was polarized at a
      slightly anodic potential (+0.5 V vs SCE in CH3CN). This method literally allows
      for switching on/off the formation of SAMs under "soft" conditions. Moreover the
      cyclic disulfide-based SAM was completely desorbed at this potential contrary to
      the facilitated deposition of a ferrocene-labeled alkanethiol. Such a strikingly
      contrasting behavior could be explained by an energetically favored release of
      the thioctic-based SAM through homolytic cleavage of the Au-S bond followed by
      intramolecular cyclization of the generated thiyl diradicals. Moreover, the
      absence of a discernible transient faradaic current response during the potential
      assisted adsorption/desorption of the redox-labeled cyclic disulfide led us to
      conclude in a potential-dependent reversible surface reaction where no electron
      is released or consumed. These results provide new insights into the formation of
      disulfide-based SAMs on gold but also raise some fundamental questions about the
      intimate mechanism involved in the facilitated adsorption/desorption of SAMs
      under electrode polarization. Finally, the possibility to easily and selectively
      address the formation/removal of thioctic-based SAMs on gold by applying a
      moderate cathodic/anodic potential offers another degree of freedom in tailoring
      their properties and in controlling their self-assembly, nanostructuration,
      and/or release.

PMID- 23540685
TI  - Synovial sarcoma mechanisms: a series of unfortunate events.
AB  - Human synovial sarcoma is caused by a chromosome translocation, which fuses DNA
      encoding SSX to that encoding the SS18 protein. Kadoch and Crabtree now show that
      the resulting cellular transformation stems from disruption of the normal
      architecture and function of the human SWI/SNF (BAF) complex.

PMID- 23540686
TI  - Ring around the Ro-sie: RNA-mediated alterations of PNPase activity.
AB  - Chen et al. demonstrate a new way by which noncoding RNAs tailor the function of
      multicomponent complexes. They show that a noncoding RNA interacts with an
      exoribonuclease, altering its substrate specificity and enzymatic activity by
      serving as a ribonucleoprotein scaffold and, perhaps, a gate for entry of the RNA
      substrate.

PMID- 23540687
TI  - Cullins getting undressed by the protein exchange factor Cand1.
AB  - Cullin-RING ubiquitin ligase complexes (CRLs) rely on a vast array of adaptor
      proteins to recognize their substrates. Pierce et al. and related papers from
      Zemla et al. and Wu et al. in Nature Communications show that Cand1 promotes
      exchange of adaptor proteins to regulate the CRL repertoire.

PMID- 23540688
TI  - Lessons from the cancer genome.
AB  - Systematic studies of the cancer genome have exploded in recent years. These
      studies have revealed scores of new cancer genes, including many in processes not
      previously known to be causal targets in cancer. The genes affect cell signaling,
      chromatin, and epigenomic regulation; RNA splicing; protein homeostasis;
      metabolism; and lineage maturation. Still, cancer genomics is in its infancy.
      Much work remains to complete the mutational catalog in primary tumors and across
      the natural history of cancer, to connect recurrent genomic alterations to
      altered pathways and acquired cellular vulnerabilities, and to use this
      information to guide the development and application of therapies.

PMID- 23540689
TI  - Interplay between the cancer genome and epigenome.
AB  - Cancer arises as a consequence of cumulative disruptions to cellular growth
      control with Darwinian selection for those heritable changes that provide the
      greatest clonal advantage. These traits can be acquired and stably maintained by
      either genetic or epigenetic means. Here, we explore the ways in which
      alterations in the genome and epigenome influence each other and cooperate to
      promote oncogenic transformation. Disruption of epigenomic control is pervasive
      in malignancy and can be classified as an enabling characteristic of cancer
      cells, akin to genome instability and mutation.

PMID- 23540690
TI  - Influence of metabolism on epigenetics and disease.
AB  - Chemical modifications of histones and DNA, such as histone methylation, histone
      acetylation, and DNA methylation, play critical roles in epigenetic gene
      regulation. Many of the enzymes that add or remove such chemical modifications
      are known, or might be suspected, to be sensitive to changes in intracellular
      metabolism. This knowledge provides a conceptual foundation for understanding how
      mutations in the metabolic enzymes SDH, FH, and IDH can result in cancer and,
      more broadly, for how alterations in metabolism and nutrition might contribute to
      disease. Here, we review literature pertinent to hypothetical connections between
      metabolic and epigenetic states in eukaryotic cells.

PMID- 23540691
TI  - Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic
      fusion in synovial sarcoma.
AB  - Recent exon sequencing studies have revealed that over 20% of human tumors have
      mutations in subunits of mSWI/SNF (BAF) complexes. To investigate the underlying
      mechanism, we studied human synovial sarcoma (SS), in which transformation
      results from the translocation of exactly 78 amino acids of SSX to the SS18
      subunit of BAF complexes. We demonstrate that the SS18-SSX fusion protein
      competes for assembly with wild-type SS18, forming an altered complex lacking the
      tumor suppressor BAF47 (hSNF5). The altered complex binds the Sox2 locus and
      reverses polycomb-mediated repression, resulting in Sox2 activation. Sox2 is
      uniformly expressed in SS tumors and is essential for proliferation. Increasing
      the concentration of wild-type SS18 leads to reassembly of wild-type complexes
      retargeted away from the Sox2 locus, polycomb-mediated repression of Sox2, and
      cessation of proliferation. This mechanism of transformation depends on only two
      amino acids of SSX, providing a potential foundation for therapeutic
      intervention.

PMID- 23540692
TI  - Hijacking the neuronal NMDAR signaling circuit to promote tumor growth and
      invasion.
AB  - Glutamate and its receptor N-methyl-D-aspartate receptor (NMDAR) have been
      associated with cancer, although their functions are not fully understood.
      Herein, we implicate glutamate-driven NMDAR signaling in a mouse model of
      pancreatic neuroendocrine tumorigenesis (PNET) and in selected human cancers.
      NMDAR was upregulated at the periphery of PNET tumors, particularly invasive
      fronts. Moreover, elevated coexpression of NMDAR and glutamate exporters
      correlated with poor prognosis in cancer patients. Treatment of a tumor-derived
      cell line with NMDAR antagonists impaired cancer cell proliferation and invasion.
      Flow conditions mimicking interstitial fluid pressure induced autologous
      glutamate secretion, activating NMDAR and its downstream MEK-MAPK and CaMK
      effectors, thereby promoting invasiveness. Congruently, pharmacological
      inhibition of NMDAR in mice with PNET reduced tumor growth and invasiveness.
      Therefore, beyond its traditional role in neurons, NMDAR may be activated in
      human tumors by fluid flow consequent to higher interstitial pressure, inducing
      an autocrine glutamate signaling circuit with resultant stimulation of
      malignancy.

PMID- 23540693
TI  - Endogenous retrotransposition activates oncogenic pathways in hepatocellular
      carcinoma.
AB  - LINE-1 (L1) retrotransposons are mobile genetic elements comprising ~17% of the
      human genome. New L1 insertions can profoundly alter gene function and cause
      disease, though their significance in cancer remains unclear. Here, we applied
      enhanced retrotransposon capture sequencing (RC-seq) to 19 hepatocellular
      carcinoma (HCC) genomes and elucidated two archetypal L1-mediated mechanisms
      enabling tumorigenesis. In the first example, 4/19 (21.1%) donors presented
      germline retrotransposition events in the tumor suppressor mutated in colorectal
      cancers (MCC). MCC expression was ablated in each case, enabling oncogenic beta
      catenin/Wnt signaling. In the second example, suppression of tumorigenicity 18
      (ST18) was activated by a tumor-specific L1 insertion. Experimental assays
      confirmed that the L1 interrupted a negative feedback loop by blocking ST18
      repression of its enhancer. ST18 was also frequently amplified in HCC nodules
      from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene.
      These proof-of-principle results substantiate L1-mediated retrotransposition as
      an important etiological factor in HCC.

PMID- 23540694
TI  - Somatic mutations of the immunoglobulin framework are generally required for
      broad and potent HIV-1 neutralization.
AB  - Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are
      therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly
      somatically mutated and generated by a fraction of HIV-1-infected individuals
      several years after infection. Antibodies typically accumulate mutations in the
      complementarity determining region (CDR) loops, which usually contact the
      antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that
      are both resistant to and less tolerant of mutations. Here, we report that in
      contrast to most antibodies, including those with limited HIV-1 neutralizing
      activity, most bNAbs require somatic mutations in their FWRs. Structural and
      functional analyses reveal that somatic mutations in FWR residues enhance breadth
      and potency by providing increased flexibility and/or direct antigen contact.
      Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and
      their unusual contribution to potency and breadth should be considered in HIV-1
      vaccine design.

PMID- 23540695
TI  - Glioblastoma stem cells generate vascular pericytes to support vessel function
      and tumor growth.
AB  - Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display
      cellular hierarchies containing self-renewing tumorigenic glioma stem cells
      (GSCs). Because GSCs often reside in perivascular niches and may undergo
      mesenchymal differentiation, we interrogated GSC potential to generate vascular
      pericytes. Here, we show that GSCs give rise to pericytes to support vessel
      function and tumor growth. In vivo cell lineage tracing with constitutive and
      lineage-specific fluorescent reporters demonstrated that GSCs generate the
      majority of vascular pericytes. Selective elimination of GSC-derived pericytes
      disrupts the neovasculature and potently inhibits tumor growth. Analysis of human
      GBM specimens showed that most pericytes are derived from neoplastic cells. GSCs
      are recruited toward endothelial cells via the SDF-1/CXCR4 axis and are induced
      to become pericytes predominantly by transforming growth factor beta. Thus, GSCs
      contribute to vascular pericytes that may actively remodel perivascular niches.
      Therapeutic targeting of GSC-derived pericytes may effectively block tumor
      progression and improve antiangiogenic therapy.

PMID- 23540696
TI  - Heritable remodeling of yeast multicellularity by an environmentally responsive
      prion.
AB  - Prion proteins undergo self-sustaining conformational conversions that heritably
      alter their activities. Many of these proteins operate at pivotal positions in
      determining how genotype is translated into phenotype. But the breadth of prion
      influences on biology and their evolutionary significance are just beginning to
      be explored. We report that a prion formed by the Mot3 transcription factor,
      [MOT3(+)], governs the acquisition of facultative multicellularity in the budding
      yeast Saccharomyces cerevisiae. The traits governed by [MOT3(+)] involved both
      gains and losses of Mot3 regulatory activity. [MOT3(+)]-dependent expression of
      FLO11, a major determinant of cell-cell adhesion, produced diverse lineage
      specific multicellular phenotypes in response to nutrient deprivation. The prions
      themselves were induced by ethanol and eliminated by hypoxia-conditions that
      occur sequentially in the natural respiro-fermentative cycles of yeast
      populations. These data demonstrate that prions can act as environmentally
      responsive molecular determinants of multicellularity and contribute to the
      natural morphological diversity of budding yeast.

PMID- 23540697
TI  - An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA.
AB  - Many bacteria contain an ortholog of the Ro autoantigen, a ring-shaped protein
      that binds noncoding RNAs (ncRNAs) called Y RNAs. In the only studied bacterium,
      Deinococcus radiodurans, the Ro ortholog Rsr functions in heat-stress-induced
      ribosomal RNA (rRNA) maturation and starvation-induced rRNA decay. However, the
      mechanism by which this conserved protein and its associated ncRNAs act has been
      obscure. We report that Rsr and the exoribonuclease polynucleotide phosphorylase
      (PNPase) form an RNA degradation machine that is scaffolded by Y RNA. Single
      particle electron microscopy, followed by docking of atomic models into the
      reconstruction, suggests that Rsr channels single-stranded RNA into the PNPase
      cavity. Biochemical assays reveal that Rsr and Y RNA adapt PNPase for effective
      degradation of structured RNAs. A Ro ortholog and ncRNA also associate with
      PNPase in Salmonella Typhimurium. Our studies identify another ribonucleoprotein
      machine and demonstrate that ncRNA, by tethering a protein cofactor, can alter
      the substrate specificity of an enzyme.

PMID- 23540698
TI  - The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access
      H1-containing heterochromatin.
AB  - Nucleosome remodelers of the DDM1/Lsh family are required for DNA methylation of
      transposable elements, but the reason for this is unknown. How DDM1 interacts
      with other methylation pathways, such as small-RNA-directed DNA methylation
      (RdDM), which is thought to mediate plant asymmetric methylation through DRM
      enzymes, is also unclear. Here, we show that most asymmetric methylation is
      facilitated by DDM1 and mediated by the methyltransferase CMT2 separately from
      RdDM. We find that heterochromatic sequences preferentially require DDM1 for DNA
      methylation and that this preference depends on linker histone H1. RdDM is
      instead inhibited by heterochromatin and absolutely requires the nucleosome
      remodeler DRD1. Together, DDM1 and RdDM mediate nearly all transposon methylation
      and collaborate to repress transposition and regulate the methylation and
      expression of genes. Our results indicate that DDM1 provides DNA
      methyltransferases access to H1-containing heterochromatin to allow stable
      silencing of transposable elements in cooperation with the RdDM pathway.

PMID- 23540699
TI  - Phospholipase Cepsilon hydrolyzes perinuclear phosphatidylinositol 4-phosphate to
      regulate cardiac hypertrophy.
AB  - Phospholipase Cepsilon (PLCepsilon) is a multifunctional enzyme implicated in
      cardiovascular, pancreatic, and inflammatory functions. Here we show that
      conditional deletion of PLCepsilon in mouse cardiac myocytes protects from stress
      induced pathological hypertrophy. PLCepsilon small interfering RNA (siRNA) in
      ventricular myocytes decreases endothelin-1 (ET-1)-dependent elevation of nuclear
      calcium and activation of nuclear protein kinase D (PKD). PLCepsilon scaffolded
      to muscle-specific A kinase-anchoring protein (mAKAP), along with PKCepsilon and
      PKD, localizes these components at or near the nuclear envelope, and this complex
      is required for nuclear PKD activation. Phosphatidylinositol 4-phosphate (PI4P)
      is identified as a perinuclear substrate in the Golgi apparatus for mAKAP
      scaffolded PLCepsilon. We conclude that perinuclear PLCepsilon, scaffolded to
      mAKAP in cardiac myocytes, responds to hypertrophic stimuli to generate
      diacylglycerol (DAG) from PI4P in the Golgi apparatus, in close proximity to the
      nuclear envelope, to regulate activation of nuclear PKD and hypertrophic
      signaling pathways.

PMID- 23540700
TI  - Metformin retards aging in C. elegans by altering microbial folate and methionine
      metabolism.
AB  - The biguanide drug metformin is widely prescribed to treat type 2 diabetes and
      metabolic syndrome, but its mode of action remains uncertain. Metformin also
      increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli.
      This bacterium exerts complex nutritional and pathogenic effects on its nematode
      predator/host that impact health and aging. We report that metformin increases
      lifespan by altering microbial folate and methionine metabolism. Alterations in
      metformin-induced longevity by mutation of worm methionine synthase (metr-1) and
      S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine
      restriction in the host, consistent with action of this drug as a dietary
      restriction mimetic. Metformin increases or decreases worm lifespan, depending on
      E. coli strain metformin sensitivity and glucose concentration. In mammals, the
      intestinal microbiome influences host metabolism, including development of
      metabolic disease. Thus, metformin-induced alteration of microbial metabolism
      could contribute to therapeutic efficacy-and also to its side effects, which
      include folate deficiency and gastrointestinal upset.

PMID- 23540701
TI  - Diet-induced developmental acceleration independent of TOR and insulin in C.
      elegans.
AB  - Dietary composition has major effects on physiology. Here, we show that
      developmental rate, reproduction, and lifespan are altered in C. elegans fed
      Comamonas DA1877 relative to those fed a standard E. coli OP50 diet. We identify
      a set of genes that change in expression in response to this diet and use the
      promoter of one of these (acdh-1) as a dietary sensor. Remarkably, the effects on
      transcription and development occur even when Comamonas DA1877 is diluted with
      another diet, suggesting that Comamonas DA1877 generates a signal that is sensed
      by the nematode. Surprisingly, the developmental effect is independent from TOR
      and insulin signaling. Rather, Comamonas DA1877 affects cyclic gene expression
      during molting, likely through the nuclear hormone receptor NHR-23. Altogether,
      our findings indicate that different bacteria elicit various responses via
      distinct mechanisms, which has implications for diseases such as obesity and the
      interactions between the human microbiome and intestinal cells.

PMID- 23540703
TI  - SnapShot: inflammasomes.

PMID- 23540702
TI  - Integration of metabolic and gene regulatory networks modulates the C. elegans
      dietary response.
AB  - Expression profiles are tailored according to dietary input. However, the
      networks that control dietary responses remain largely uncharacterized. Here, we
      combine forward and reverse genetic screens to delineate a network of 184 genes
      that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find
      that perturbation of a mitochondrial network composed of enzymes involved in
      amino acid metabolism and the TCA cycle affects the dietary response. In humans,
      mutations in the corresponding genes cause inborn diseases of amino acid
      metabolism, most of which are treated by dietary intervention. We identify
      several transcription factors (TFs) that mediate the changes in gene expression
      upon metabolic network perturbations. Altogether, our findings unveil a
      transcriptional response system that is poised to sense dietary cues and
      metabolic imbalances, illustrating extensive communication between metabolic
      networks in the mitochondria and gene regulatory networks in the nucleus.

PMID- 23540705
TI  - Highly reduced double-decker single-molecule magnets exhibiting slow magnetic
      relaxation.
AB  - F64Pc2Ln (1Ln, Ln = Tb or Lu) represent the first halogenated phthalocyanine
      double-decker lanthanide complexes, and 1Tb exhibits single-molecule magnet
      properties as revealed by solid-state magnetometry. The fluorine substituents of
      the phthalocyanine rings have a dramatic effect on the redox properties of the
      F64Pc2Ln complexes, namely, a stabilization of their reduced states.
      Electrochemical and spectroelectrochemical measurements demonstrate that the 1Tb(
      /2-) and 1Tb(2-/3-) couples exhibit redox reversibility and that the 1Tb(-),
      1Tb(2-) and 1Tb(3-) species may be prepared by bulk electrolysis in acetone. Low
      temperature MCD studies reveal for the first time magnetization hystereses for
      the super-reduced dianionic and trianionic states of Pc2Ln.

PMID- 23540706
TI  - A concise total synthesis of pyrovellerolactone using a rhodium-catalyzed [(3 +
      2) + 2] carbocyclization reaction.
AB  - A concise and highly convergent three-step total synthesis of the lactarane
      natural product, pyrovellerolactone, is described. The key step involves a regio-
      and diastereoselective rhodium-catalyzed [(3 + 2) + 2] carbocyclization of an
      alkenylidenecyclopropane with a 4-hydroxybut-2-ynoate followed by an in situ
      intramolecular lactonization to generate the tricyclic core in a single
      operation. This represents the first example of a higher-order [3 + 2 + 2]
      carbocyclization reaction in total synthesis, which is likely to provide an
      important strategy for the construction of related targets within this
      sesquiterpene family.

PMID- 23540707
TI  - The future of prodrugs - design by quantum mechanics methods.
AB  - INTRODUCTION: The revolution in computational chemistry greatly impacted the drug
      design and delivery fields, in general, and recently the utilization of the
      prodrug approach in particular. The use of ab initio, semiempirical and molecular
      mechanics methods to understand organic reaction mechanisms of certain processes,
      especially intramolecular reactions, has opened the door to design and to rapidly
      produce safe and efficacious delivery of a wide range of active small molecule
      and biotherapeutics such as prodrugs. AREAS COVERED: This article provides the
      readers with a concise overview of this modern approach to prodrug design. The
      use of computational approaches, such as density functional theory (DFT),
      semiempirical and ab initio molecular orbital methods, in modern prodrugs design
      will be discussed. The novel prodrug approach to be reported in this review
      implies prodrug design based on enzyme model (mimicking enzyme catalysis) that
      has been utilized to understand how enzymes work. The tool used in the design is
      a computational approach consisting of calculations using molecular orbital and
      molecular mechanics methods (DFT, ab initio and MM2) and correlations between
      experimental and calculated values of intramolecular processes that were used to
      understand the mechanism by which enzymes might exert their high rates catalysis.
      EXPERT OPINION: The future of prodrug technology is exciting yet extremely
      challenging. Advances must be made in understanding the chemistry of many organic
      reactions that can be effectively utilized to enable the development of even more
      types of prodrugs. Despite the increase in the number of marketed prodrugs, we
      have only started to appreciate the potential of the prodrug approach in modern
      drug development, and the coming years will witness many novel prodrug
      innovations.

PMID- 23540708
TI  - Comparison and repeatability of keratometric and corneal power measurements
      obtained by Orbscan II, Pentacam, and Galilei corneal tomography systems.
AB  - PURPOSE: To assess the repeatability and comparability of corneal power and
      central corneal thickness (CCT) measurements obtained using Orbscan II (Bausch &
      Lomb), Pentacam (Oculus), and Galilei (Ziemer) tomographers. DESIGN: Prospective,
      comparative study. METHODS: setting: Departments of Ophthalmology, University of
      Auckland and Auckland District Health Board, Auckland, New Zealand. study
      population: Thirty eyes of 30 healthy participants. observations. CCT and corneal
      power measured using Orbscan II, Pentacam, and Galilei tomography. main outcome
      measures: Degree of agreement in and repeatability of CCT and corneal power
      measures. RESULTS: Orbscan II measured significantly lower CCT compared with
      Pentacam (20 MUm; P < .0005) and Galilei (18 MUm; P < .0005). The Orbscan II had
      wide limits of agreement when compared with both the Galilei (-11 to 47 MUm) and
      Pentacam (-88 to 47 MUm). For each device, the intraclass correlation coefficient
      for CCT was higher than 0.9. The coefficient of variation ranged from 0.33% to
      0.93%. There was no significant difference in mean steep keratometry or mean flat
      keratometry between instrument pairs. However, there was poor agreement in flat
      keratometry and steep keratometry obtained by Orbscan II compared with those
      obtained by the Galilei and Pentacam. CONCLUSIONS: The keratometry and pachymetry
      measurements obtained by Orbscan II, Pentcam, and Galilei tomographers were
      sufficiently disparate that the 3 devices could not be considered equivalent. All
      3 devices demonstrated a high level of repeatability, although the Galilei
      exhibited the best repeatability.

PMID- 23540709
TI  - Partial lamellar sclerouvectomy of ciliary body tumors in a Korean population.
AB  - PURPOSE: To describe the clinical characteristics of ciliary body tumors,
      surgical outcomes, and factors associated with poor visual outcome and
      metastasis. DESIGN: Retrospective case series. METHODS: Medical records of 27
      patients with ciliary body tumors who underwent partial lamellar sclerouvectomy
      in a single-center setting (Seoul, South Korea) were reviewed. Surgical outcomes
      were reviewed, and clinical characteristics were analyzed with respect to visual
      prognosis and globe retention rate. RESULTS: Tumors were diagnosed
      histopathologically as benign in 8 (30%) cases and as melanoma in 19 (70%) cases.
      Patients had a median age of 48 years. The median follow-up was 3.5 years (range,
      0.5 to 6 years). The tumors had a median diameter of 11 mm and a median thickness
      of 9 mm. The globe was retained in 20 (74%) eyes, with visual acuity of 20/400 or
      better in 13 (48%) eyes and 20/40 or better in 6 (22%) eyes. Choroidal
      involvement of tumor (P = .003), larger diameter of tumor (P < .001), and thicker
      tumor (P < .001) were associated with poor visual outcome. Local recurrence (P =
      .003) and presence of epithelioid cells (P = .040) were predictive factors for
      metastasis in melanoma patients. Kaplan-Meier estimates of metastasis-free
      survival at 3 and 5 years for melanoma patients were 82% and 55%, respectively.
      CONCLUSIONS: Partial lamellar sclerouvectomy is a reasonable primary therapeutic
      option in ciliary body tumors, and good visual prognosis is expected in selected
      cases.

PMID- 23540710
TI  - Endophthalmitis isolates and antibiotic susceptibilities: a 10-year review of
      culture-proven cases.
AB  - PURPOSE: To investigate the spectrum of organisms causing culture-proven
      endophthalmitis and their susceptibilities to commonly used antimicrobial agents
      over 10 years. DESIGN: Retrospective, noncomparative, consecutive case series.
      METHODS: Medical records were reviewed of all cases with culture-proven
      endophthalmitis at a single institution from 2002 through 2011. The outcome
      measures included all intravitreal isolates identified as well as antibiotic
      susceptibilities. RESULTS: A total of 448 organisms were isolated during the
      study interval. The most common organisms identified were Staphylococcus
      epidermidis in 30.1% (135/448), Streptococcus viridians group in 10.9% (49/448),
      Staphylococcus aureus in 7.8% (35/448), Candida albicans in 5.8% (26/443), other
      coagulase-negative staphylococci in 6.0% (27/448), Propionibacterium acnes in
      4.7% (21/448), and Pseudomonas aeruginosa in 3.1% (14/448). Overall, 327 (72.9%)
      of 448 isolates were gram-positive organisms, 48 (10.7%) of 448 isolates were
      gram-negative organisms, 71 (15.8%) of 448 isolates were fungi, and 2 (0.4%) of
      448 isolates were viruses. For gram-positive organisms, susceptibilities were the
      following: vancomycin, 100%; gentamicin, 88.0%; sulfamethoxazole/trimethoprim,
      77.5%; levofloxacin, 58.5%; oxacillin, 54.7%; ciprofloxacin, 51.0%; gatifloxacin,
      51.0%; and moxifloxacin, 47.0%. For gram-negative organisms, susceptibilities
      were the following: ceftazidime, 100%; levofloxacin, 100%; ciprofloxacin, 95.0%;
      tobramycin, 90.6%; gentamicin, 80.6%; and sulfamethoxazole/trimethoprim, 59.4%.
      CONCLUSIONS: In the current study, no single antibiotic provided coverage for all
      of the microbes isolated from eyes with endophthalmitis. Combination therapy
      generally is the recommendation as the initial empiric treatment of suspected
      bacterial endophthalmitis. Appropriate history and characteristic clinical
      features may guide the use of initial antifungal agents.

PMID- 23540711
TI  - Foveal thickness in healthy fellow eyes of patients with unilateral macular
      holes.
AB  - PURPOSE: To compare the morphologic parameters of ophthalmoscopically and
      tomographically normal foveae of the fellow eyes of patients with a unilateral
      macular hole (MH), other unilateral retinal diseases, and healthy eyes. DESIGN:
      Observational, cross-sectional study. METHODS: Of the 849 subjects studied, 183
      eyes were excluded because they had an abnormal vitreofoveal interface that might
      have affected the foveal thickness. The average regional retinal thicknesses of
      the Early Treatment Diabetic Retinopathy Study sectors determined by spectral
      domain optical coherence tomography were compared among 160 patients with MH, 175
      patients with epiretinal membrane, 145 patients with retinal vein occlusion, and
      186 healthy subjects. The foveal depression was quantified as the foveal pit
      depth divided by the foveal pit diameter. RESULTS: The fovea (1 mm) and central
      fovea were significantly thinner in the MH group (243 and 192 MUm) than in the
      other groups (P < .0001). There were no significant differences in the thickness
      of the fovea and central fovea among the eyes with epiretinal membrane (254 and
      203 MUm) or retinal vein occlusion (251 and 202 MUm) or in the healthy group (254
      and 201 MUm). The foveal depression was significantly greater in the MH group
      (0.063) than in the retinal vein occlusion group (0.059) or in the healthy group
      (0.058; P = .014 and P = .0014, respectively). Multiple regression analyses
      showed that a thinner fovea and a deeper foveal depression were associated
      significantly with the presence of MH (P = .0054 to P < .0001). CONCLUSIONS:
      These results suggest that patients with MH have unique foveal morphologic
      features that predispose them to MH development.

PMID- 23540712
TI  - Optical quality comparison of conventional and hole-visian implantable collamer
      lens at different degrees of decentering.
AB  - PURPOSE: To compare the optical quality of implantable Collamer lens (ICL) with
      and without central hole (Hole ICL and conventional ICL) at different degrees of
      decentering. DESIGN: Experimental laboratory investigation. METHODS: Wavefront
      aberrations of the -3, -6, and -12 diopter (D) V4b and -3, -6, and -12 D V4c ICLs
      were measured in 3 conditions-centered and decentered 0.3 and 0.6 mm-at 3-mm and
      4.5-mm pupils. The root mean square of total higher order aberrations, trefoil,
      coma, tetrafoil, secondary astigmatism, and spherical aberration were evaluated.
      In addition, point spread function and simulated retinal images of ICLs were
      calculated from the wavefront aberrations for each ICL and all conditions of
      decentering at 4.5-mm pupil. RESULTS: No statistically significant differences in
      any Zernike coefficient terms evaluated were found between conventional and Hole
      ICLs for any ICL powers and pupils evaluated (P > .05). We could not appreciate
      differences in the point spread function images and in simulated retinal images.
      Regarding the effect of the ICL decentration, coma aberration increased
      significantly with ICL decentration (P < .05), although these differences were
      not visible in the point spread function images and simulated retinal images. The
      ICL decentration was affected in the same manner on the conventional and Hole
      ICLs. CONCLUSIONS: The outcomes showed good and comparable optical quality of the
      conventional and Hole ICLs for all ICL powers evaluated. Despite that coma
      aberration increased with ICL decentering, these values were clinically
      negligible and did not have a significant effect on the simulated visual
      performance.

PMID- 23540713
TI  - Asymmetric collapse in biomimetic complex coacervates revealed by local polymer
      and water dynamics.
AB  - Complex coacervation is a phenomenon characterized by the association of
      oppositely charged polyelectrolytes into micrometer-scale liquid condensates.
      This process is the purported first step in the formation of underwater adhesives
      by sessile marine organisms, as well as the process harnessed for the formation
      of new synthetic and protein-based contemporary materials. Efforts to understand
      the physical nature of complex coacervates are important for developing robust
      adhesives, injectable materials, or novel drug delivery vehicles for biomedical
      applications; however, their internal fluidity necessitates the use of in situ
      characterization strategies of their local dynamic properties, capabilities not
      offered by conventional techniques such as X-ray scattering, microscopy, or bulk
      rheological measurements. Herein, we employ the novel magnetic resonance
      technique Overhauser dynamic nuclear polarization enhanced nuclear magnetic
      resonance (DNP), together with electron paramagnetic resonance (EPR) line shape
      analysis, to concurrently quantify local molecular and hydration dynamics, with
      species- and site-specificity. We observe striking differences in the structure
      and dynamics of the protein-based biomimetic complex coacervates from their
      synthetic analogues, which is an asymmetric collapse of the polyelectrolyte
      constituents. From this study we suggest charge heterogeneity within a given
      polyelectrolyte chain to be an important parameter by which the internal
      structure of complex coacervates may be tuned. Acquiring molecular-level insight
      to the internal structure and dynamics of dynamic polymer complexes in water
      through the in situ characterization of site- and species-specific local polymer
      and hydration dynamics should be a promising general approach that has not been
      widely employed for materials characterization.

PMID- 23540715
TI  - Mounting a strategic offense: fighting tumor vasculature with oncolytic viruses.
AB  - Blood supply within a tumor drives progression and ultimately allows for
      metastasis. Many anticancer therapies target tumor vasculature, but their
      individual effectiveness is limited because they induce indirect cell death.
      Agents that disrupt nascent and/or established tumor vasculature while
      simultaneously killing cancer cells would certainly have a greater impact.
      Oncolytic virotherapy utilizes attenuated viruses that replicate specifically
      within a tumor. They induce cytotoxicity through a combination of direct cell
      lysis, antitumor immune stimulation, and recently identified antitumor vascular
      effects. This review summarizes the novel preclinical and clinical evidence
      regarding the antitumor vascular effects of oncolytic viruses, which include
      infection and lysis of tumor endothelial cells, natural or genetically engineered
      antiangiogenic properties, and combination therapy with clinically approved
      antivascular agents.

PMID- 23540716
TI  - CD95 in cancer: tool or target?
AB  - The role of CD95 (Fas/Apo1) in cancer has been a matter of debate for over 30
      years. First discovered as an apoptosis-inducing molecule, CD95 soon emerged as a
      potential anticancer therapy. Yet accumulating evidence indicates a profound role
      for CD95 in alternative nonapoptotic signaling pathways that increase
      tumorigenesis. This fact challenges the initial clinical idea of using CD95 as a
      'tumor killer' while setting the stage for clinical studies targeting the
      nonapoptotic signaling branch of CD95. This review summarizes the findings
      surrounding manipulation of the CD95 pathway for cancer therapy, considering how
      one receptor can both promote and prevent cell growth.

PMID- 23540714
TI  - Attenuating myocardial ischemia by targeting A2B adenosine receptors.
AB  - Myocardial ischemia is associated with profound tissue hypoxia due to an
      imbalance in oxygen supply and demand, and studies of hypoxia-elicited adaptive
      responses during myocardial ischemia revealed a cardioprotective role for the
      signaling molecule adenosine. In ischemic human hearts, the A2B adenosine
      receptor (ADORA2B) is selectively induced. Functional studies in genetic models
      show that ADORA2B signaling attenuates myocardial infarction by adapting
      metabolism towards more oxygen efficient utilization of carbohydrates. This
      adenosine-mediated cardio-adaptive response involves the transcription factor
      hypoxia-inducible factor HIF1alpha and the circadian rhythm protein PER2. In this
      article, we discuss advances in the understanding of adenosine-elicited
      cardioprotection with particular emphasis on ADORA2B, its downstream targets, and
      the implications for novel strategies to prevent or treat myocardial ischemia.

PMID- 23540717
TI  - Implications of Medicare procedure volumes on resident education.
AB  - BACKGROUND: Preparation of future general surgeons requires the ongoing
      assessment of projected case experience. METHODS: Surgical procedures (2005-2008)
      were abstracted from the Centers for Medicare and Medicaid Services inpatient
      National Claims History Part A 100% Nearline File for all general surgeons. The
      most frequent Medicare surgical procedures and physician caseloads were compared
      by practice population. RESULTS: Over 5 million procedures were evaluated, with
      procedures decreasing over time in urban and large rural areas. A total of 15
      procedures comprised the top 10 for all population/year categories. The most
      frequent surgical procedures were similar in rural and urban areas. Rural
      surgeons' caseloads consisted of a higher proportion of endoscopic procedures.
      CONCLUSIONS: The most common Medicare general surgery procedures are similar
      across population areas and are required experience for residents. Separate
      surgical educational programs for urban and rural general surgeons may not be
      necessary to provide adequate care to rural patients.

PMID- 23540719
TI  - Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no
      immediate impact on patient outcome.
AB  - INTRODUCTION: A tumor-promoting impact of neutrophils and macrophages has been
      demonstrated in some cancers. However, the prognostic significance of innate
      immune cells in patients with non-small cell lung cancer (NSCLC) is unclear.
      METHODS: A total of 335 consecutive patients resected for stage I-IIIA NSCLC were
      assessed for CD66b(+) neutrophils and CD163(+) macrophages in the tumor nests and
      adjacent stromal tissue by immunohistochemistry in whole tissue sections using
      stereology as well as automatic computerized quantification. Findings were
      correlated with clinical and histopathological parameters, baseline blood
      inflammatory markers (C-reactive protein (CRP) and white blood cell count (WBC)).
      Endpoints were recurrence-free survival (RFS) and overall survival (OS). RESULTS:
      Elevated CRP above median (101 nmol/l) and WBC above median (8.6 * 10(9)cells/l)
      were associated with poor RFS (p <= 0.002) and poor OS (p <= 0.01). Higher
      density of CD66b(+) in tumor nests and stroma was associated with elevated CRP
      and WBC, squamous cell histology, tumor size, and necrosis (p <= 0.01). Higher
      density of CD163(+) macrophages in tumor nests and stroma was associated with
      elevated CRP and lymph node metastases (p <= 0.049). The densities of tumor nest
      CD66b(+) neutrophils and CD163(+) macrophages were not significantly correlated
      with RFS or OS, irrespective of assessment method. CONCLUSIONS: The densities of
      tumor-associated CD66b(+) neutrophils and CD163(+) macrophages in NSCLC were
      correlated with adverse prognostic factors and systemic blood inflammation
      markers, but not directly correlated with RFS or OS. Further research of chronic
      inflammation in NSCLC is warranted.

PMID- 23540718
TI  - Tumor response and health-related quality of life in clinically selected patients
      from Asia with advanced non-small-cell lung cancer treated with first-line
      gefitinib: post hoc analyses from the IPASS study.
AB  - BACKGROUND: In IPASS (NCT00322452), progression-free survival (PFS, primary
      endpoint) was significantly longer with first-line gefitinib versus
      carboplatin/paclitaxel in never/light ex-smokers with advanced pulmonary
      adenocarcinoma in Asia, both in the overall intent-to-treat (ITT) population and
      in the EGFR mutation-positive subgroup. To further characterize the clinical
      relevance of these data, we investigated objective response rate (ORR) and health
      related quality of life (HRQoL) in patients treated with gefitinib. METHODS:
      Objective response was assessed (RECIST) 6-weekly (previously reported). Post hoc
      assessments included median time to response, median duration of response and
      change in tumor size. The analysis of response population included those patients
      treated with gefitinib who responded (n = 262 from ITT; n = 94 from EGFR mutation
      positive subgroup). The percentage of patients with deterioration in HRQoL
      (Functional Assessment of Cancer Therapy-Lung [FACT-L], Trial Outcome Index
      [TOI]) and symptoms (Lung Cancer Subscale [LCS]) at 4 months post-randomization
      was analyzed according to progression status (EFQ population grouped by
      progressors/non-progressors in both treatment arms). The ORR (ITT) and incidence
      of skin rash/acne (evaluable-for-safety) were summarized. RESULTS: In patients
      whose tumors responded to gefitinib, median time to response was 6.1 weeks in the
      ITT population (n = 262) and 6.0 weeks in the EGFR mutation-positive subgroup (n
      = 94); median duration of response was 9.7 and 8.7 months in these groups,
      respectively. There was significant tumor shrinkage with gefitinib. A greater
      percentage of patients in the EFQ population whose tumors progressed experienced
      deterioration in HRQoL and symptoms at 4 months versus patients whose tumors did
      not progress (FACT-L 33.7% vs 16.3%; TOI 33.7% vs 13.2%; LCS 31.7% vs 15.5%). In
      the gefitinib arm of the EFS population, incidence of rash was 75.8% and 68.1% in
      EGFR mutation-positive and -negative subgroups, respectively (with ORR for the
      gefitinib arm of the ITT 71.2% vs 1.1%, respectively). CONCLUSIONS: Patients
      whose tumors responded to first-line gefitinib experienced significant tumor
      shrinkage and a rapid, durable response. Deterioration in HRQoL and lung cancer
      symptoms at 4 months post-randomization was found to be associated with tumor
      progression, highlighting the role of patient-reported outcomes in the evaluation
      of advanced NSCLC disease. Rash was not supported as a predictive marker of
      response to gefitinib.

PMID- 23540720
TI  - Sagittal abdominal diameter as a marker for epicardial adipose tissue in
      premenopausal women.
AB  - OBJECTIVE: Accumulation of epicardial (EAT) adipose tissue is associated with the
      development of an unfavorable metabolic risk profile. Gold standard methods used
      to assess this fat depot are not routinely applicable in the clinic.
      Anthropometric measures, including the sagittal abdominal diameter (SAD), have
      emerged as surrogate markers of visceral obesity. We determined the relationship
      between EAT measurement and cardiometabolic risk parameters and the potential use
      of the SAD, compared with other anthropometric parameters, as a practical
      estimation of EAT. MATERIALS/METHODS: Sixty-seven premenopausal women were
      evaluated. The anthropometric parameters that were measured included waist
      circumference, SAD, body mass index and waist-to-hip ratio. EAT was determined by
      echocardiogram. Visceral adipose tissue (VAT) was determined by abdominal
      ultrasound. Insulin sensitivity was assessed by the hyperglycemic clamp. RESULTS:
      The accumulation of EAT was correlated with impaired insulin sensitivity and
      decreased adiponectin. All of the anthropometric measurements were correlated
      with EAT. Interestingly, EAT was most significantly correlated with the SAD. From
      the ROC analysis, we found that the SAD measurements were very accurate,
      presenting the highest area under the curve for EAT (0.81; p<0.01) when compared
      with the other measurements. In the multiple linear regression analysis, EAT was
      moderately predicted by the SAD (R2=0.25; p<0.001). CONCLUSION: SAD, a simple
      anthropometric measure, accurately estimated EAT and thus represents a clinically
      useful non-invasive marker that can identify patients with EAT accumulation.

PMID- 23540721
TI  - Validation of the in vivo volumetric wear measurement for total knee prostheses
      in model-based RSA.
AB  - Implant failure related to polyethylene wear remains an important issue in total
      knee arthroplasty. Polyethylene wear is usually assessed in vivo by measuring the
      remaining insert thickness on X-ray images of the knee. To reflect the amount of
      wear debris more accurately, a 3-dimensional overlap measurement has been
      suggested, which is based on implant component models which are matched on
      calibrated stereo X-ray images using model-based roentgen stereophotogrammatic
      analysis. The goal of this study was to determine the influence of pose
      estimation, insert thickness deviation and variation in the femoral-tibial
      contact location on the accuracy and precision of the measurement using
      simulations and a phantom experiment. We found that the pose estimation was the
      largest source of variation. The 95% prediction interval varied between 111 and
      283 mm(3), which is approximately 100-200% of the detected volumetric wear.
      Insert thickness variation resulted in prediction intervals of 74-174 mm(3).
      Variation of the femoral-tibial contact location in the phantom experiment gave a
      prediction interval of 40 mm(3). Large differences in the detected wear volume
      were found for different flexion angles. At most 56% of the true wear volume was
      detected (129 of 230 mm(3), 30 degrees  of flexion). In summary, both the
      accuracy and precision of the volumetric wear measurement were low. The
      prediction interval of the volumetric wear measurement is at least as large as
      the measurement outcome itself. This is an important limitation to the
      applicability of the volumetric wear measurement in clinical practice and further
      clinical validation is required.

PMID- 23540722
TI  - Proximal femur bone strength estimated by a computationally fast finite element
      analysis in a sideways fall configuration.
AB  - Finite element (FE) analysis based on quantitative computed tomography (QCT)
      images is an emerging tool to estimate bone strength in a specific patient or
      specimen; however, it is limited by the computational power required and the
      associated time required to generate and solve the models. Thus, our objective
      was to develop a fast, validated method to estimate whole bone structural
      stiffness and failure load in addition to a sensitivity analysis of varying
      boundary conditions. We performed QCT scans on twenty fresh-frozen proximal
      femurs (age: 77+/-13 years) and mechanically tested the femurs in a configuration
      that simulated a sideways fall on the hip. We used custom software to generate
      the FE models with boundary conditions corresponding to the mechanical tests and
      solved the linear models to estimate bone structural stiffness and estimated
      failure load. For the sensitivity analysis, we varied the internal rotation angle
      of the femoral neck from -30 degrees  to 45 degrees  at 15 degrees  intervals and
      estimated structural stiffness at each angle. We found both the FE estimates of
      structural stiffness (R(2)=0.89, p<0.01) and failure load (R(2)=0.81, p<0.01) to
      be in high agreement with the values found by mechanical testing. An important
      advantage of these methods was that the models of approximately 500,000 elements
      took less than 11 min to solve using a standard desktop workstation. In this
      study we developed and validated a method to quickly and accurately estimate
      proximal femur structural stiffness and failure load using QCT-driven FE methods.

PMID- 23540723
TI  - Empirical assessment of dynamic hamstring function during human walking.
AB  - The hamstrings are often associated with the development of crouch gait, a
      fatiguing form of walking characterized by excessive hip flexion, knee flexion
      and ankle dorsiflexion during stance. However, recent studies have called into
      question whether abnormally active hamstrings induce the limb to move into a
      crouch posture. The purpose of this study was to directly measure the influence
      of the hamstrings on limb posture during stance. Nineteen healthy young adults
      walked on an instrumented treadmill at their preferred speed. A 90 ms pulse train
      was used to stimulate the medial hamstrings during either terminal swing or
      loading response of random gait cycles. Induced motion was defined as the
      difference in joint angle trajectories between stimulated and non-stimulated
      strides. A dynamic musculoskeletal simulation of normal gait was generated and
      similarly perturbed by increasing hamstring excitation. The experiments show that
      hamstring stimulation induced a significant increase in posterior pelvic tilt,
      knee flexion and ankle dorsiflexion during stance, while having relatively less
      influence on the hip angular trajectory. The induced motion patterns were similar
      whether the hamstrings were stimulated during late swing or early stance, and
      were generally consistent with the direction of induced motion predicted by gait
      simulation models. Hence, we conclude that overactive hamstrings have the
      potential to induce the limb to move toward a crouch gait posture.

PMID- 23540724
TI  - Considerations when loading spinal finite element models with predicted muscle
      forces from inverse static analyses.
AB  - Mostly simplified loads were used in biomechanical finite element (FE) studies of
      the spine because of a lack of data on muscular physiological loading. Inverse
      static (IS) models allow the prediction of muscle forces for predefined postures.
      A combination of both mechanical approaches - FE and IS - appears to allow a more
      realistic modeling. However, it is unknown what deviations are to be expected
      when muscle forces calculated for models with rigid vertebrae and fixed centers
      of rotation, as generally found in IS models, are applied to a FE model with
      elastic vertebrae and discs. The aim of this study was to determine the effects
      of these disagreements. Muscle forces were estimated for 20 degrees  flexion and
      10 degrees  extension in an IS model and transferred to a FE model. The effects
      of the elasticity of bony structures (rigid vs. elastic) and the definition of
      the center of rotation (fixed vs. non-fixed) were quantified using the deviation
      of actual intervertebral rotation (IVR) of the FE model and the targeted IVR from
      the IS model. For extension, the elasticity of the vertebrae had only a minor
      effect on IVRs, whereas a non-fixed center of rotation increased the IVR
      deviation on average by 0.5 degrees  per segment. For flexion, a combination of
      the two parameters increased IVR deviation on average by 1 degrees  per segment.
      When loading FE models with predicted muscle forces from IS analyses, the main
      limitations in the IS model - rigidity of the segments and the fixed centers of
      rotation - must be considered.

PMID- 23540725
TI  - Counter-effect of constrained dynamic loading on osteoporosis in ovariectomized
      mice.
AB  - In recent years, dynamic mechanical loading has been shown to effectively enhance
      bone remodeling. The current study attempted to research the counter-effect of
      constrained dynamic loading on osteoporosis (OP) in ovariectomized (OVX) mice.
      Female Kunming (KM) mice were randomly divided into 2 groups: SHAM and OVX. The
      right ulnas of the OVX mice were subjected to a 4-week constrained dynamic
      loading protocol, and the mechanical properties, trabecular micromorphology
      parameters and biochemical indices of osteogenesis were evaluated. We detected
      higher levels of tissue alkaline phosphatase (AKP) and serum bone gamma
      carboxyglutamic-acid-containing proteins (BGPs), better trabecular
      micromorphology parameters and ulnar mechanical properties in the loading group
      than in the nonloading group. In summary, constrained dynamic loading could
      prevent ovariectomy-induced osteoporosis by facilitating osteogenesis, improving
      trabecular microstructure and enhancing bone mechanical properties.

PMID- 23540726
TI  - Approaching families on the subject of organ donation: a phenomenological study
      of the experience of healthcare professionals.
AB  - The aim of this study was to explore healthcare professionals' experiences and
      gain a deeper understanding of interactions with families when approaching the
      subject of organ donation. A hermeneutic phenomenological approach was used to
      explore the participants' experiences. Data were collected through a combination
      of observation and in-depth interviews with nurses, physicians and hospital
      chaplains recruited from two intensive care units (ICUs) in a Norwegian
      university hospital. A thematic analysis was used to analyse the data, and three
      main themes emerged from this analysis: crucial timing, challenging conversations
      and conflicting expectations. The results revealed that the situation was of a
      sensitive nature and that finding the best possible time to address the issue in
      a meaningful manner was a challenge. Respect for the patients' wishes and the
      families' decisions were an expressed value among the participants, but
      conflicting expectations about bringing up the subject were also present. This
      study contributes to the understanding of healthcare professionals' challenges
      when they are facing brain death as an inevitable outcome of a patient's clinical
      condition and must approach families on the subject of organ donation.

PMID- 23540727
TI  - The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in immune
      thrombocytopenia.
AB  - BACKGROUND: Although Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are known
      to trigger immune thrombocytopenia (ITP), the manifestations of EBV and CMV in
      ITP spleen tissues continue to be poorly understood. METHODS: Our research
      retrospectively reviewed a total of 42 ITP patients and 20 healthy control cases
      from the West China Hospital of Sichuan University from 2008 to 2012. Patients'
      characteristics, preoperative platelet counts, and the expression of EBV and CMV
      in spleen tissue were analyzed. RESULTS: No statistically significant differences
      were identified for age and gender between the ITP group and the healthy control
      group. The comparison of these two categories (the ITP group and the control
      group) showed substantial variations in the expression of EBV and CMV: nine
      (21.4%) and eight (19%) ITP patients had a positive expression of EBV and CMV,
      compared with none and one patient in the control group, respectively. In the EBV
      ITP group, patients with a positive EBV expression revealed appreciably decreased
      preoperative platelet count compared with patients with a negative EBV
      expression. No other statistically significant difference was found in the CMV
      group. CONCLUSION: We have demonstrated the presence of both EBV and CMV
      infections in the spleen tissue of ITP patients. EBV infections were implicated
      in the reduced platelet counts in ITP.

PMID- 23540728
TI  - Doppler flow patterns in the right ventricle-to-pulmonary artery shunt and neo
      aorta in infants with single right ventricle anomalies: impact on outcome after
      initial staged palliations.
AB  - BACKGROUND: A Pediatric Heart Network trial compared outcomes in infants with
      single right ventricle anomalies undergoing Norwood procedures randomized to
      modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery
      shunt (RVPAS). Doppler patterns in the neo-aorta and RVPAS may characterize
      physiologic changes after staged palliations that affect outcomes and right
      ventricular (RV) function. METHODS: Neo-aortic cardiac index (CI), retrograde
      fraction (RF) in the descending aorta and RVPAS conduit, RVPAS/neo-aortic
      systolic ejection time ratio, and systolic/diastolic (S/D) ratio were measured
      early after Norwood, before stage II palliation, and at 14 months. These
      parameters were compared with transplantation-free survival, length of hospital
      stay, and RV functional indices. RESULTS: In 529 subjects (mean follow-up period,
      3.0 +/- 2.1 years), neo-aortic CI and descending aortic RF were significantly
      higher in the MBTS cohort after Norwood. The RVPAS RF averaged <25% at both
      interstage intervals. Higher pre-stage II descending aortic RF was correlated
      with lower RV ejection fraction (R = -0.24; P = .032) at 14 months for the MBTS
      cohort. Higher post-Norwood CI (5.6 vs 4.4 L/min/m(2), P = .04) and lower S/D
      ratio (1.40 vs 1.68, P = .01) were correlated with better interstage
      transplantation-free survival for the RVPAS cohort. No other Doppler flow
      patterns were correlated with outcomes. CONCLUSIONS: After the Norwood procedure,
      infants tolerated significant descending aortic RF (MBTS) and conduit RF (RVPAS),
      with little correlation with clinical outcomes or RV function. Neo-aortic CI,
      ejection time, and S/D ratios also had limited correlations with outcomes or RV
      function, but higher post-Norwood neo-aortic CI and lower S/D ratio were
      correlated with better interstage survival in those with RVPAS.

PMID- 23540731
TI  - Copper-catalyzed diastereoselective arylation of tryptophan derivatives: total
      synthesis of (+)-naseseazines A and B.
AB  - A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction
      proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline
      products in one step from simple starting materials. The utility of this
      transformation is highlighted in the five-step syntheses of the natural products
      (+)-naseseazine A and B.

PMID- 23540732
TI  - Isolated cervical spinal canal stenosis at C-1 in the pediatric population and in
      Williams syndrome.
AB  - OBJECT: Isolated cervical canal stenosis at the level of the atlas (C-1) is a
      rare cause of cervical myelopathy in the pediatric population. It has been
      associated with several genetic disorders including spondyloepiphysial dysplasia
      congenita, Down syndrome, and Klippel-Feil syndrome. The purpose of this study is
      to highlight the authors' experience with 4 additional pediatric cases, review
      the literature, and report a new association of this disease with Williams
      syndrome. METHODS: The medical records and radiological imaging studies of 4
      patients treated at Texas Children's Hospital for symptomatic hypoplasia of the
      atlas were retrospectively reviewed. Pertinent patient demographic data, clinical
      presentation, imaging findings, and outcomes after surgery were recorded. A
      thorough literature review was performed, allowing the authors to compare and
      contrast their 4 cases to surgical cases already published in the literature.
      RESULTS: There were 11 boys and 1 girl in the aggregate series. The average age
      of the patients was 7 years (range 13 months-14 years), and the duration of
      symptoms prior to presentation was 6 months (range 0-36 months). The mean
      sagittal diameter of the spinal canal at the level of the atlas measured from the
      posterior aspect of the dens to the anterior aspect of the arch of C-1 was 11.9
      mm (range 8.3-16 mm) in the aggregate series. In 2 new pediatric patients with
      hypoplasia of the atlas the disease was associated with Williams syndrome, which
      has not been previously described. Patients in the aggregate series were followed
      for an average of 18 months (range 3-50 months). Laminectomy of C-1 provided
      neurological improvement in all patients who presented. CONCLUSIONS: Isolated
      cervical spinal canal stenosis at the level of the atlas is a rare cause of
      cervical myelopathy. The authors hope that this report will prompt clinicians to
      consider it when searching for the origin of signs and symptoms of cervical
      myelopathy, especially in children.

PMID- 23540733
TI  - Anatomical feasibility of C-2 pedicle screw fixation: the effect of variable
      angle interpolation of axial CT scans.
AB  - OBJECT: Anatomical variability of the C-2 pedicle poses a challenge for C-2
      fixation. The use of multidimensional CT scanning is not widely used but might be
      an asset to preoperative planning. Careful preoperative planning is imperative
      for instrumentation at C-2. Fine-cut, noncontrast CT scanning is a useful tool
      for delineating anatomy; however, the axis of the images is not always along the
      anatomical axis of the vertebra in question. The authors evaluated the
      suitability of C-2 pedicles for screw placement by using OsiriX (Pixmeo) software
      to change the gantry angle of CT angiograms to measure the anatomical dimensions
      of the C-2 pedicle. METHODS: The authors conducted a retrospective review of CT
      angiograms of the head and neck from 47 trauma patients seen consecutively at
      George Washington University Hospital. For each patient, 3 independent observers
      determined length and width of each C-2 pedicle (94 samples) by using OsiriX.
      OsiriX is a DICOM viewer that enables navigation and visualization in
      multidimensional imaging, such as 3D imaging, which was used for this study. Sex
      specific measurements were also determined. Vertebral anatomy was studied to
      determine whether aberrant anatomy would preclude pedicle fixation. Statistical
      analyses were performed. RESULTS: Of the 47 patients, 27 were male. Overall mean
      C-2 pedicle widths and lengths were 8.272 +/- 1.364 mm and 27.052 +/- 3.471 mm,
      respectively. The average widths and lengths of the pedicle in female patients
      were 8.040 +/- 1.262 mm and 27.241 +/- 2.731 mm, respectively, and those in male
      patients were 8.444 +/- 1.414 mm and 26.913 +/- 3.933 mm, respectively. The sex
      difference was statistically significant for width (p = 0.012) but not for length
      (p = 0.41). On the basis of width, the percentages of pedicles that could
      tolerate a 3.5-mm and 4.0-mm screw were 98% and 97%, respectively. Vertebral
      anatomy precluded screw length greater than 14 mm for only 3 patients.
      CONCLUSIONS: Using multidimensional CT or 3D imaging, the authors found that C-2
      pedicles in over 90% of patients could tolerate 3.5-mm and 4.0-mm pedicle screws.
      Vertebral anatomy precluded use of screw lengths greater than 14 mm for only 3
      (6%) of 47 patients. Therefore, the C-2 pedicle might be more tolerant of
      fixation than previously reported.

PMID- 23540734
TI  - Anatomical feasibility of performing a nerve transfer from the femoral branch to
      bilateral pelvic nerves in a cadaver: a potential method to restore bladder
      function following proximal spinal cord injury.
AB  - OBJECT: Nerve transfers are an effective means of restoring control to paralyzed
      somatic muscle groups and have recently been shown to be effective in denervated
      detrusor muscle in a canine model. A cadaveric study was performed to examine the
      anatomical feasibility of transferring femoral muscular nerve branches to vesical
      branches of the pelvic nerve as a method of potentially restoring innervation to
      control the detrusor muscle in humans. METHODS: Twenty cadavers were dissected
      bilaterally to expose pelvic and femoral muscular nerve branches. Ease of access
      and ability to transfer the nerves were assessed, as were nerve cross-sectional
      areas. RESULTS: The pelvic nerve was accessed at the base of the bladder,
      inferior to the ureter, and accompanied by inferior vesical vessels. Muscular
      branches of the femoral nerve to the vastus medialis and intermedius muscles (L-3
      and L-4 origins) were followed distally for 17.4 +/- 0.8 cm. Two muscle branches
      were split from the femoral nerve trunk, and tunneled inferior to the inguinal
      ligament. One branch was moved medially toward the base of the bladder and linked
      to the ipsilateral pelvic nerve. The second branch was tunneled superior to the
      bladder and linked to the contralateral pelvic nerve. The cross-sectional area of
      the pelvic nerve vesical branch was 2.60 +/- 0.169 mm(2) (mean +/- SEM), and the
      femoral nerve branch at the suggested transection site was 4.40 +/- 0.41 mm2.
      CONCLUSIONS: Use of femoral nerve muscular branches from the vastus medialis and
      intermedius muscles for heterotopic nerve transfer of bilateral pelvic nerves is
      surgically feasible, based on anatomical location and cross-sectional areas.

PMID- 23540735
TI  - A less-invasive cervical laminoplasty for spondylotic myelopathy that preserves
      the semispinalis cervicis muscles and nuchal ligament.
AB  - OBJECT: Modified cervical laminoplasty techniques have been developed to reduce
      postoperative axial neck pain and preserve function in patients with cervical
      spondylotic myelopathy (CSM). However, the previous studies demonstrating
      satisfactory surgical outcomes had a retrospective design. Here, the authors
      aimed to prospectively evaluate the 2-year outcomes of a modified cervical
      laminoplasty technique for CSM that preserves the paravertebral muscles. METHODS:
      Outcomes were analyzed for 40 patients (22 men and 18 women; mean age, 66.6
      years; age range 44-92 years) with CSM who underwent C4-6 laminoplasty with C-3
      and C-7 partial laminectomies or C-3 total and C-7 partial laminectomies and
      received hydroxyapatite spacers. Neurological, pain severity, and spinal
      radiographic evaluations were performed preoperatively and at 3, 6, 12, 18, and
      24 months postoperatively. Plain radiography and MRI of the cervical spine were
      performed to evaluate the range of motion (ROM), sagittal alignment, and cross
      sectional areas of the deep extensor muscles. The extent of bone-spacer bonding
      and bony union at the gutter was assessed by CT. RESULTS: The mean preoperative
      Japanese Orthopaedic Association CSM score was 10.2, but it increased to 14.4 by
      24 months after surgery. Eleven patients had axial neck pain preoperatively, but
      only 3 reported mild pain at 24 months, and in all 3 cases the pain was mild. The
      mean angle of lordosis was 11.7 degrees  preoperatively and 12.0 degrees  2 years
      postoperatively. Although the ROM at the C2-7 levels was significantly reduced 3
      months postoperatively, an increasing trend was observed up to 12 months, and 86%
      of the preoperative ROM was achieved by 2 years postoperatively. The mean
      paravertebral muscle cross-sectional areas were 833 +/- 215 mm(2) preoperatively
      and 763 +/- 197 mm(2) 24 months postoperatively, but the difference was not
      statistically significant. The rates of bone-spacer bonding and bony union at the
      gutter were low during the early stages but increased to 90% and 93%,
      respectively, by 2 years after surgery. CONCLUSIONS: The modified laminoplasty
      technique used in this study ensured very good neurological status and ROM after
      2 years and was associated with low incidences of axial neck pain and serious
      complications. This simple and easy operative method could benefit future
      laminoplasty protocols.

PMID- 23540736
TI  - Syringomyelia.

PMID- 23540737
TI  - Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors
      (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains.
AB  - Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non
      nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological
      activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3
      isopropyl and 3-iodine group, respectively, exhibited highly potent activity
      against wild-type HIV-1 strains and those resistant to reverse transcriptase
      inhibitors (RTIs). The diastereoisomers of 26-trans and 26-cis were synthesized
      separately and confirmed with HPLC and NOESY spectra. The 26-trans isomers had an
      activity about 400-fold more potent than that of 26-cis. The pair of 26-trans
      enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity
      index (SI) of 75000, was highly effective against a panel of RTIs-resistant
      strains with single (Y181C and K103N) or double (A17) mutations in reverse
      transcriptase. The results suggest that these novel pyridinone derivatives have
      the potential to be further developed as new antiretroviral drugs with improved
      antiviral efficacy and drug resistance profile.

PMID- 23540739
TI  - Cardio-oncology for the 21st century: introduction.

PMID- 23540738
TI  - A 62-year-old woman with osteogenic sarcoma in the contralateral breast 15 years
      after treatment for breast cancer.

PMID- 23540740
TI  - Cardiac testing to manage cardiovascular risk in cancer patients.
AB  - Cardiovascular toxicity is one of the most feared complications of cancer
      treatment. Recent advances in oncologic therapies have resulted in improved
      cancer outcomes but also a new set of cardiovascular adverse effects. Common
      toxicities include left ventricular dysfunction/heart failure, hypertension, and
      myocardial ischemia. Accurate risk stratification allows avoidance of potentially
      harmful treatments in those patients at greatest risk while maintaining the
      ability to deliver high doses of effective therapies to the lower-risk
      population. Cardiac investigations, including echocardiography, nuclear imaging,
      magnetic resonance imaging, biomarker measurement, blood pressure monitoring,
      electrocardiography, stress testing, and invasive angiography, can help to risk
      stratify selected patients. In this review, common complications are discussed in
      terms of the factors used to identify patients with elevated risk, the monitoring
      strategies available, and selected interventions that have been used to modify
      outcomes in patients identified as being at high risk for cardiac complications
      of cancer treatment.

PMID- 23540741
TI  - Cardiovascular toxicities of cancer chemotherapy.
AB  - Cancer chemotherapy has improved over the years with the advent of newer agents,
      including more targeted chemotherapeutic drugs, resulting in better patient
      survival. However, with continued use and patient exposure to these drugs,
      important cardiovascular adverse effects are becoming realized, such as left
      ventricular dysfunction and heart failure, myocardial ischemia, hypertension,
      arrhythmias, and pulmonary arterial hypertension. In this article, we review the
      most common cardiovascular toxicities and their related pathophysiology that
      occur with the use of these agents.

PMID- 23540742
TI  - Cardiovascular toxicities of biological therapies.
AB  - The development of biological therapy is based on growing knowledge regarding the
      molecular changes required in cells for the development and progression of cancer
      to occur. Molecular targeted therapy is designed to inhibit the major molecular
      pathways identified as essential for a specific development. This information, in
      turn, has led to new opportunities for the treatment of cancer. Normal cells,
      however, are also dependent on these pathways to maintain their function and,
      consequently, their survival. Interfering with this function in normal cells may
      result in the risk of serious adverse effects. One serious adverse effect is the
      risk of cardiovascular dysfunction. Some targeted therapies, eg, treatment with
      monoclonal antibodies or angiogenesis inhibitors, have shown an increased risk of
      cardiac events. Their influence on the cardiovascular system, however, seems to
      be transient, but there is scarce information about their long-term effects for
      general use. Previous experience with long-term survivors, in whom the risk for
      cardiac disease seems to increase in subsequent years, has led to concern about
      patients treated with molecular therapy. This review assesses the currently
      available knowledge about the risk of cardiotoxicity in targeted therapy for
      general use.

PMID- 23540743
TI  - Cardiac complications after radical radiotherapy.
AB  - Improvements in cancer therapy have led to increasing numbers of cancer
      survivors, and the long-term complications of these treatments are now becoming
      apparent. This article presents the current knowledge of adverse cardiovascular
      effects of radiotherapy to the chest. Medline literature searches relating to the
      cardiac complications of radiotherapy and subsequent prognosis were conducted.
      Potential adverse effects of mediastinal irradiation are numerous and can include
      coronary artery disease, pericarditis, cardiomyopathy, and valvular disease.
      Damage seems to be related to radiation dose, volume of irradiated heart, age at
      exposure, technique of chest irradiation, and patient-specific factors. The
      advent of technology and the newer sophisticated techniques in treatment planning
      and delivery are expected to decrease the incidence of cardiovascular diseases
      after radiation of the mediastinal structures. In any case, patients subjected to
      irradiation of the mediastinal structures require close multidisciplinary
      clinical monitoring.

PMID- 23540744
TI  - Strategies to prevent and treat cardiovascular risk in cancer patients.
AB  - Cardiotoxicity due to cancer treatment is of rising concern, for both
      cardiologists and oncologists, because it may have a significant impact on cancer
      patient management and outcome. The most typical manifestation of cardiotoxicity
      is a hypokinetic cardiomyopathy leading to heart failure. However, the spectrum
      of the toxic effects that can impair the cardiovascular system may also include
      acute coronary syndromes, hypertension, arrhythmias, and thromboembolic events.
      Patients undergoing cancer treatment are more vulnerable to cardiovascular
      injuries, and their risk of premature cardiovascular disease and death is higher
      than that of the general population. Prevention of cardiotoxicity remains the
      most important strategy, and several measures, including cardiac function
      monitoring, limitation of chemotherapy dose, use of anthracycline analogues and
      cardioprotectants, and early detection of myocardial cell injury by biomarkers,
      have been proposed. The response to modern heart failure therapy of cancer
      treatment-induced cardiomyopathy has never been evaluated in clinical trials, and
      currently there are no definitive guidelines. Although it is likely that
      medications used for other forms of cardiomyopathy, particularly angiotensin
      converting enzyme inhibitors and beta-blockers, may be highly effective, there is
      still some unjustified concern regarding their use in cancer patients. Specific
      guidelines that take cardiologic conditions of cancer patients into account are
      currently lacking and need to be developed.

PMID- 23540745
TI  - Infiltrative cardiomyopathy and pericardial disease.
AB  - Infiltrative cardiomyopathies and pericardial involvement frequently complicate
      the course of malignancy and usually portend a poor outcome. The initial
      presentation is usually non-specific, and timely diagnosis requires a high index
      of suspicion on the part of both the oncologist and the consulting cardiologist.
      The goal of this review was to illustrate three potential infiltrative conditions
      of the myocardium with associated cardiomyopathies that are encountered in cancer
      patients: cardiac amyloid, iron overload, and lymphomatous infiltration. We also
      review the common manifestations of pericardial disease in cancer patients and
      outline optimal management.

PMID- 23540746
TI  - Managing the risks of cardiac therapy in cancer patients.
AB  - The purpose of this review was to highlight the more commonly used cardiac
      medications that should be closely monitored or possibly discontinued during
      cancer therapy. Often, older cancer patients are taking multiple pharmacotherapy
      agents for the treatment or prevention of cardiac disease when they face
      decisions about cancer treatment. Concurrent administration of drugs can result
      either in increased toxicity or decreased efficacy of either therapy. The
      benefits of the cardiac medications must be weighed against the effects of cancer
      therapy, and the role of drug metabolism also must be considered. For example,
      the benefits of cardiac medications such as anti-platelet agents, important in
      treating coronary artery disease, and anti-thrombotic agents, important for
      stroke prevention in atrial fibrillation, must be evaluated against an increased
      risk of bleeding during cancer therapy. It should be noted that some cardiac
      medications which act on hormonal receptors can theoretically stimulate growth of
      certain cancers. The concomitant management of cardiac therapy and cancer therapy
      is a common challenge in today's aging population.

PMID- 23540747
TI  - Exercise therapy as treatment for cardiovascular and oncologic disease after a
      diagnosis of early-stage cancer.
AB  - Advances in early detection and adjuvant therapy have led to dramatic
      improvements in longevity after a cancer diagnosis. As a result, there are ~13.7
      million cancer survivors alive in the United States, with this figure projected
      to increase to 18 million in 2022. Despite improvements in the 5-year relative
      survival rates, cancer patients with early-stage disease not only remain at high
      risk of cancer recurrence but also have sufficient longevity to now be at risk
      for late effects of adjuvant therapy, particularly cardiovascular disease (CVD).
      Against this background, we review here the risk factors common to cancer and CVD
      as well as the extant evidence supporting the potential efficacy of exercise
      therapy to modify the risk of cancer-specific and CVD-specific mortality in
      persons with cancer. We also evaluate evidence from clinical studies
      investigating the effects of structured exercise therapy to modify risk factors
      common to cancer and CVD. Findings of this review indicate that several major
      biomarkers/risk factors are predictive of both recurrence as well as non-cancer
      mortality in persons diagnosed with cancer. Such information is important to
      health professionals providing disease-risk screening as well as informing
      effective management strategies in long-term cancer survivors. In terms of the
      latter, there is growing but preliminary evidence that exercise may be
      efficacious in lowering both recurrence and CVD risk in cancer patients.

PMID- 23540748
TI  - Asymptomatic cardiac toxicity in long-term cancer survivors: defining the
      population and recommendations for surveillance.
AB  - Advances in the treatment of pediatric and adult cancer have reduced the
      mortality rates from these disorders and have led to an ever-increasing
      population of long-term survivors. Chemotherapy and radiotherapy may cause
      premature cardiac disease that may be asymptomatic or symptomatic. All patients
      exposed to chemotherapy with cardiotoxic potential or chest radiotherapy have
      stage A heart failure and the goal of surveillance and treatment is to prevent
      progression to stages B-D. Screening strategies, including the use of biomarkers,
      echocardiography, and expert opinion surveillance and treatment recommendations,
      are presented.

PMID- 23540749
TI  - [Vaccines in history, or a history of vaccines].

PMID- 23540750
TI  - [Regional cerebral oxygen saturation as a marker of hemodynamic state following
      cardiac surgery].
AB  - INTRODUCTION: Regional cerebral oxygen saturation (rSO2) is a measure of the
      general state of perfusion and oxygenation. We aim to analyze the relationship
      between this and various hemodynamic and respiratory parameters. PATIENTS AND
      METHODS: Forty-three patients, operated on between October 2011 and July 2012,
      were included in this prospective observational descriptive study. The following
      parameters were measured: mean arterial pressure, both arterial and central
      venous oxygen saturation and partial pressures of oxygen and carbon dioxide, and
      lactate levels. From these parameters, the oxygenation index and the oxygen
      extraction ratio were calculated. These measurements were studied to evaluate
      whether rSO2 correlated significantly with the other parameters. RESULTS: The
      average age and weight of the patients were 27.3 months and 9.2 kg, respectively.
      The rSO2 correlated positively with both central venous oxygen saturation
      (r=0.73, P<.01) and mean arterial pressure (r=0.59, P<.01), and negatively with
      the oxygen extraction ratio (r=-0.7, P<.01). No correlation was found with the
      respiratory parameters. Concordance analysis established an acceptable Kappa
      index (> 0.4) between the rSO2 and central venous oxygen saturation, and between
      the rSO2 and oxygen extraction ratio. CONCLUSIONS: Regional cerebral oxygen
      saturation correlates well with hemodynamic parameters - mean arterial pressure,
      venous saturation, and the tissue oxygen extraction. However, it does not
      correlate with respiratory parameters.

PMID- 23540751
TI  - Structural and physical properties diversity of new CaCu5-type related europium
      platinum borides.
AB  - Three novel europium platinum borides have been synthesized by arc melting of
      constituent elements and subsequent annealing. They were characterized by X-ray
      powder and single-crystal diffraction: EuPt4B, CeCo4B type, P6/mmm, a =
      0.56167(2) nm, c = 0.74399(3) nm; Eu3Pt7B2, Ca3Al7Cu2 type as an ordered variant
      of PuNi3, R3m, a = 0.55477(2) nm, c = 2.2896(1) nm; and Eu5Pt18B(6-x), a new
      unique structure type, Fmmm, a = 0.55813(3) nm, b = 0.95476(5) nm, c = 3.51578(2)
      nm. These compounds belong to the CaCu5 family of structures, revealing a
      stacking sequence of CaCu5-type slabs with different structural units: CaCu5 and
      CeCo3B2 type in EuPt4B; CeCo3B2 and Laves MgCu2 type in Eu3Pt7B2; and CaCu5-,
      CeCo3B2-, and site-exchange ThCr2Si2-type slabs in Eu5Pt18B(6-x). The striking
      motif in the Eu5Pt18B(6-x) structure is the boron-centered Pt tetrahedron [BPt4],
      which build chains running along the a axis and plays a decisive role in the
      structure arrangement by linking the terminal fragments of repeating blocks of
      fused Eu polyhedra. Physical properties of two compounds, EuPt4B and Eu3Pt7B2,
      were studied. Both compounds were found to order magnetically at 36 and 57 K,
      respectively. For EuPt4B a mixed-valence state of the Eu atom was confirmed via
      magnetic and specific heat measurements. Moreover, the Sommerfeld value of the
      specific heat of Eu3Pt7B2 was found to be extraordinarily large, on the order of
      0.2 J/mol K(2).

PMID- 23540752
TI  - Chemisorption of cyanogen chloride by spinel ferrite magnetic nanoparticles.
AB  - Spinel ferrite magnetic nanoparticles, MnFe2O4, NiFe2O4, and CoFe2O4, were
      synthesized and used as gas-phase adsorbents for the removal of cyanogen chloride
      from dry air. Fixed-bed adsorption breakthrough experiments show adsorption wave
      behavior at the leading edge of the breakthrough curve that is not typical of
      physically adsorbed species. Fourier transform infrared spectroscopy (FTIR)
      results indicate that CK is reacting with the spinel ferrite surface and forming
      a carbamate species. The reaction is shown to be a function of the hydroxyl
      groups and adsorbed water on the surface of the particles as well as the metallic
      composition of the particles. The surface reaction decreases the remnant and
      saturation magnetism of the MnFe2O4 and CoFe2O4 particles by approximately 25%.

PMID- 23540753
TI  - The diagnostic evaluation of MelaFind multi-spectral objective computer vision
      system.
AB  - INTRODUCTION: Over 75,000 people in the United States were diagnosed with
      melanoma in 2012. The incidence of melanoma continues to increase over time and
      early detection is currently the most promising strategy to decrease melanoma
      related morbidity and mortality. Currently, most physicians perform skin cancer
      screenings with the unaided eye. However, the FDA recently approved, MelaFind, a
      multispectral objective computer vision system to assist dermatologists in making
      more accurate biopsy decisions to facilitate early melanoma diagnosis. AREAS
      COVERED: This review covers the sensitivity and specificity, limitations and
      clinical role of MelaFind and other devices available or under development to aid
      in the detection of melanoma. EXPERT OPINION: Physician screening with the aid of
      MelaFind device may improve detection of early melanoma and potentially reduce
      melanoma morbidity and mortality, if used widely. The strength of MelaFind is its
      high sensitivity, acceptable specificity, ease of use and objective output. Thus
      it has potential to improve biopsy decisions made by both dermatologists and less
      experienced clinicians. Currently, the use of MelaFind is not reimbursed by
      insurance and the cost, which is paid directly by the patient, will likely limit
      its use.

PMID- 23540754
TI  - Biocompatible polylactide-block-polypeptide-block-polylactide nanocarrier.
AB  - Polypeptides are successfully incorporated into poly(l-lactide) (PLLA) chains in
      a ring-opening polymerization (ROP) of l-lactide by using them as initiators. The
      resulting ABA triblock copolymers possess molecular weights up to 11000 g.mol(-1)
      and polydispersities as low as 1.13, indicating the living character of the
      polymerization process. In a nonaqueous emulsion, peptide-initiated
      polymerization of l-lactide leads to well-defined nanoparticles, consisting of
      PLLA-block-peptide-block-PLLA copolymer. These nanoparticles are easily loaded by
      dye-encapsulation and transferred into aqueous media without aggregation (average
      diameter of 100 nm) or significant dye leakage. Finally, internalization of PLLA
      block-peptide-block-PLLA nanoparticles by HeLa cells is demonstrated by a
      combination of coherent anti-Stokes Raman spectroscopy (CARS) and fluorescence
      microscopy. This demonstrates the promise of their utilization as cargo delivery
      vehicles.

PMID- 23540755
TI  - Fixation of lapidus arthrodesis with a plantar interfragmentary screw and medial
      locking plate: a report of 88 cases.
AB  - Lapidus arthrodesis is a powerful procedure that can be used to correct
      pathologic features within the forefoot or midfoot. Many different methods of
      fixation for this procedure have been reported. The use of plating constructs has
      been shown to provide increased stability compared with screw-only constructs.
      The technique we have described consists of a plantar to dorsal retrograde lag
      screw across the arthrodesis site, coupled with a low-profile medial locking
      plate. A total of 88 consecutive patients were treated with this modification of
      the Lapidus procedure by 2 surgeons and were retrospectively evaluated. All
      patients followed an early postoperative weightbearing protocol. Patient age,
      gender, follow-up duration, interval to weightbearing and radiographic fusion,
      preoperative and postoperative intermetatarsal angle, hardware removal,
      preoperative and postoperative American Orthopaedic Foot and Ankle Society
      midfoot scores, and adjunct procedures were analyzed. The mean follow-up period
      was 16.76 +/- 5.9 (range 12 to 36) months, and all healed fusions demonstrated
      radiographic union at a mean of 51 +/- 19.1 (range 40 to 89) days. The patients
      were treated with weightbearing starting a mean of 10.90 +/- 4.1 (range 5 to 28)
      days postoperatively. Complications included 15 patients (17%) requiring hardware
      removal, 2 cases (2%) of hallux varus, 6 cases (7%) of radiographic recurrent
      hallux valgus, and 2 patients (2%) with first metatarsocuneiform nonunion. The
      results of the present study have demonstrated that plantar lag screw fixation
      with medial locking plate augmentation for Lapidus arthrodesis allows for early
      weightbearing with satisfactory outcomes, improved clinical and radiographic
      alignment, and improved American Orthopaedic Foot and Ankle Society scores. 

PMID- 23540756
TI  - Incidence of repeat amputation after partial first ray amputation associated with
      diabetes mellitus and peripheral neuropathy: an 11-year review.
AB  - The reliability and durability of partial first ray amputation in patients with
      diabetes and peripheral neuropathy has recently been questioned. In an effort to
      determine the repeat amputation rate after a partial first ray amputation
      associated with diabetes mellitus and peripheral neuropathy at our institution,
      we performed an 11-year retrospective review. A total of 59 patients (40 males
      and 19 females), with a mean age of 63 (range 39 to 97) years, were included. The
      mean follow-up was 33.8 (range 1 to 123) months, with initial incision healing
      occurring in all 59 patients. Despite the initial healing, 69% developed a mean
      of 3.1 subsequent foot ulcerations at a mean of 10.5 months, 36% required
      ancillary surgical procedures, and more than 90% of patients were prescribed
      multiple courses of antibiotics at a mean of 26.6 clinic visits during the follow
      up period. A total of 25 patients (42.4%) underwent more proximal repeat
      amputation at a mean of 25 (range 1 to 97) months after the initial partial first
      ray amputation. The results of our retrospective review revealed that nearly 1 of
      every 2 patients with diabetes and peripheral neuropathy who undergo a partial
      first ray amputation will progress to a more proximal repeat amputation, despite
      initial healing. These data question the reliability and durability of this level
      of amputation as a primary procedure in this patient population. A more proximal
      level amputation, such as a balanced transmetatarsal, might provide a better
      functional and reliable residual weightbearing foot and should be considered at
      the initial presentation. This is especially true given that nearly one half of
      the patients died during the follow-up period. However, this remains a matter for
      conjecture because of the limited data available; therefore, additional
      prospective investigations are warranted.

PMID- 23540757
TI  - Chondroblastoma of the talus.
AB  - We report the case of a 13-year-old male child who presented with a painful left
      ankle. On imaging (radiography and computed tomography scan with 3-dimensional
      reconstruction views), an osteolytic lesion in the body of the talus was
      revealed. Open biopsy, curettage, and fibular bone grafting were done, and the
      specimen was sent for histopathologic examination. The histopathologic report
      confirmed the specimen to be chondroblastoma of the talus bone. Chondroblastoma
      is a rare benign cartilaginous neoplasm that accounts for approximately 1% of all
      bone tumors and characteristically arises in the epiphysis of a long bone,
      particularly the humerus, tibia, and femur. Chondroblastoma can affect people of
      all ages. It is, however, most common in children and young adults aged 10 to 20
      years. Chondroblastoma in a tarsal bone is a rare entity. Managing
      chondroblastoma of the talus with curettage and bone grafting has shown good
      outcomes. 

PMID- 23540758
TI  - The retromalleolar compression test: a useful exploratory maneuver in the
      clinical evaluation of flexor hallucis longus rupture.
AB  - The clinical examination of ruptures of the flexor hallucis longus can be
      difficult, especially spontaneous defects that arise without a definitive history
      of trauma. Advanced imaging, in particular, magnetic resonance imaging, can be a
      useful adjunct to the clinical examination. However, we believe that a simple
      clinical maneuver can be used to reliably ascertain the presence of a rupture of
      the flexor hallucis longus. 

PMID- 23540759
TI  - Fixation orientation in ankle fractures with syndesmosis injury.
AB  - Accurate reduction of the syndesmosis has been shown to be an important
      prognostic factor for functional outcome in ankle injuries that disrupt the
      syndesmosis. The purpose of the present case series was to assess the fixation
      orientation and the position of the fibula within the tibial incisura after open
      reduction and internal fixation of ankle fractures with syndesmosis injury.
      Computed tomography was used to assess the accuracy of the reduction. Twelve
      patients were included in the present case series. A ratio representing the
      relationship between the tibia and fibula and the orientation of the syndesmotic
      fixation was measured preoperatively and postoperatively and compared with the
      uninjured contralateral ankle, representing the patient's normal anatomy. The
      measurements were accomplished electronically to one tenth of 1 mm using Stentor
      Intelligent Informatics, I-site, version 3.3.1 (Phillips Electronics; Andover,
      MA). Posteriorly oriented syndesmotic fixation caused posterior translation of
      the fibula with respect to the tibia and anteriorly oriented syndesmotic fixation
      caused anterior translation.

PMID- 23540760
TI  - Dynamic ultrasonography: a cadaveric model for evaluating aseptic loosening of
      total ankle arthroplasty.
AB  - Aseptic loosening is the primary method of failure in total ankle replacements.
      Currently, loosening is defined by morphologic changes in osseous architecture
      determined by plain radiography. The loss of bone noted at diagnosis presents
      difficulties in future ankle revisions. A method by which early aseptic loosening
      could be detected before bony deformation or reaction could lead to improved
      patient outcomes. A cadaveric fresh frozen ankle specimen (mid-tibia to include
      the foot) was used in the present study. An anterior approach to the ankle was
      performed. A total ankle prosthesis was implanted in the standard fashion (Salto
      Talaris, Tornier). The initial cuts were made for a size 1 ankle, and a size 1
      ankle was implanted. Dynamic ultrasonography was used to evaluate the bone
      implant interface. The prosthesis was removed, and sequential removal of bone was
      performed at the interface of the medial tibial tray until visible motion was
      seen with flexion and extension. The reimplanted prosthesis was then re-evaluated
      using dynamic ultrasonography and dynamic and static fluoroscopy. In the loose
      prosthesis model, dynamic ultrasonography was able to determine the motion at the
      bone-prosthesis interface. Dynamic ultrasonography might be a useful tool in the
      evaluation of early loosening in a total ankle arthroplasty model.

PMID- 23540761
TI  - Invited commentary on "A prospective study of tumor and technical factors
      associated with positive margins in breast-conservation therapy for nonpalpable
      malignancy" by Reedijk et al.

PMID- 23540762
TI  - Development and validation of a colorimetric assay for simultaneous
      quantification of neutral and uronic sugars.
AB  - A colorimetric assay based on the conventional anthrone reaction was investigated
      for specific quantification of uronic acids (UA) in the presence of neutral
      sugars and/or proteins. Scanning of glucose (Glu) and glucuronic acid (GlA) was
      performed after the reaction with anthrone and a double absorbance reading was
      made, at 560 nm and at 620 nm, in order to quantify the UA and neutral sugars
      separately. The assay was implemented on binary or ternary solutions containing
      Glu, GlA and bovine serum albumin (BSA) in order to validate its specificity
      towards sugars and check possible interference with other biochemical components
      such as proteins. Statistical analysis indicated that this assay provided correct
      quantification of uronic sugars from 50 to 400 mg/l and of neutral sugars from 20
      to 80 mg/l, in the presence of proteins with concentrations reaching 600 mg/l.
      The proposed protocol can be of great interest for simultaneous determination of
      uronic and neutral sugars in complex biological samples. In particular, it can be
      used to correctly quantify the Extracellular Polymeric Substances (EPS) isolated
      from the biological matrix of many bacterial aggregates, even in the presence of
      EPS extractant such as EDTA.

PMID- 23540763
TI  - [Prevalence survey of cardiovascular risk factors in the general population in
      St. Louis (Senegal)].
AB  - BACKGROUND: Cardiovascular diseases are becoming with their risk factors a real
      health problem in Africa. The objectives of this study were to assess the
      prevalence of risk factors for cardiovascular diseases in the general population
      in Saint-Louis, Senegal. METHODOLOGY: This is a cross-sectional, descriptive and
      analytical made in May 2010, in the Senegalese aged 15, residing in the city of
      Saint-Louis, Senegal. A systematic random sampling and stratified cluster has
      been achieved. Cardiovascular risk factors for research were: hypertension,
      diabetes, dyslipidemia, smoking, obesity, physical inactivity and metabolic
      syndrome. RESULTS: The survey involved 1424 individuals with 983 women (69%). The
      average age was 43.4+/-17.8years. The prevalence of risk factors was:
      hypertension (46%), diabetes (10.4%), total cholesterol (36.3%),
      hyperLDLcholesterol (20.6%), obesity (body mass index>=30kg/m(2)) (23%),
      abdominal obesity (48.7% according to International Diabetes Federation and 33.2%
      according to National Cholesterol Education Program) physical inactivity (64.7%),
      smoking (5.8%) and metabolic syndrome (15.7%). There was predominance in women of
      risk factors except for smoking and diabetes. The overall cardiovascular risk was
      high in 24.9% according to the Framingham model, 28.8% (European Society of
      Hypertension) and 6.1% (SCORE). CONCLUSION: This survey found a high prevalence
      of cardiovascular risk factors in a general population in Senegal, predominant in
      women. This should lead to better develop a strategy to prevent cardiovascular
      diseases.

PMID- 23540764
TI  - Paediatric malaria in Greece in the era of global population mobility.
AB  - We reviewed the medical records of children admitted because of malaria to four
      tertiary-care hospitals in Greece during 1972-2002. A total of 21 cases were
      found, including 20 (95.2%) diagnosed during 2003-2012. Sixteen (76.2%) children
      had been in a malaria-endemic country within a median of 50 days before the onset
      of their symptoms. Main causes of travel were immigration to Greece and to visit
      friends and relatives (VFRs). A considerable epidemiological shift of paediatric
      malaria occurred in Greece during the past decade, which is attributed almost
      exclusively to the increase of immigrants and travellers VFRs.

PMID- 23540765
TI  - Avatars of information: towards an inclusive evolutionary synthesis.
AB  - Following the discovery that inheritance entails the interaction between genetic
      and nongenetic processes, biology is undergoing a profound mutation. This
      paradigm shift implies that the model of heredity that is emerging incorporates
      genetic and nongenetic processes. A way to integrate all forms of inheritance
      harmoniously is to consider what unifies genetic and nongenetic heredity. Here, I
      unify all sources of phenotypic variation within the concept of information and
      its avatars, discuss a major overlooked methodological problem leading to
      confounding sources of variation (namely the case of the missing heritability),
      propose new research avenues, and illustrate how putting concepts of information
      at the heart of evolutionary approaches will affect the emerging Inclusive
      Evolutionary Synthesis.

PMID- 23540766
TI  - Rapid detection of economic adulterants in fresh milk by liquid chromatography
      tandem mass spectrometry.
AB  - A method to aid in the detection of the economically driven adulteration of fresh
      milk with a range of small, nitrogen containing compounds, including melamine,
      ammeline, ammelide, cyanuric acid, allantoin, thiourea, urea, biuret, triuret,
      semicarbazide, aminotriazine, 3- and 4-aminotriazole, cyanamide, dicyandiamide,
      guanidine, choline, hydroxyproline, nitrate, and a range of amino acids, has been
      developed. (15)N2-Urea is used as an internal standard. The adulteration of milk
      with exogenous urea has previously been difficult to detect because of the
      variation in the naturally occurring levels of urea in milk. However, by
      monitoring the contaminants biuret and triuret, which comprise up to 1% of
      synthetic urea, the adulteration of milk with urea-based fertilizer can be
      detected. We estimate that to be economically viable, adulteration of the order
      of 90-4000ppm of the above adulterants would need to be added to fresh milk. For
      most of the compounds, an arbitrary detection threshold of 2ppm is therefore more
      than sufficient. For biuret, a lower detection threshold, better than 0.5ppm, is
      desirable and the sensitivity for biuret and triuret can be improved by the post
      column addition of lithium to create lithium adducts under electrospray
      ionisation. Sample handling involves a two-step solvent precipitation method that
      is deployed in a 96-well plate format, and the hydrophilic interaction liquid
      chromatography uses a rapid gradient (1.2min). Three separate injections, to
      detect the positively charged compounds, the negatively charged compounds and
      amino acids and finally the lithium adducts, are used. This rapid and qualitative
      survey method may be deployed as a second tier screening method to quickly reduce
      sample numbers indicated as irregular by an FTIR based screening system, and to
      direct analysis to appropriate quantification methods.

PMID- 23540767
TI  - Use of ultra-high pressure liquid chromatography coupled to high resolution mass
      spectrometry for fast screening in high throughput doping control.
AB  - We describe a sensitive, comprehensive and fast screening method based on liquid
      chromatography-high resolution mass spectrometry for the detection of a large
      number of analytes in sports samples. UHPLC coupled to high resolution mass
      spectrometry with polarity switching capability is applied for the rapid
      screening of a large number of analytes in human urine samples. Full scan data
      are acquired alternating both positive and negative ionisation. Collision-induced
      dissociation with positive ionisation is also performed to produce fragment ions
      to improve selectivity for some analytes. Data are reviewed as extracted ion
      chromatograms based on narrow mass/charge windows (+/-5ppm). A simple sample
      preparation method was developed, using direct enzymatic hydrolysis of
      glucuronide conjugates, followed by solid phase extraction with mixed mode ion
      exchange cartridges. Within a 10min run time (including re-equilibration) the
      method presented allows for the analysis of a large number of analytes from most
      of the classes in the World Anti-Doping Agency (WADA) Prohibited List, including
      anabolic agents, beta2-agonists, hormone antagonists and modulators, diuretics,
      stimulants, narcotics, glucocorticoids and beta-blockers, and does so while
      meeting the WADA sensitivity requirements. The high throughput of the method and
      the fast sample pre-treatment reduces analysis cost and increases productivity.
      The method presented has been used for the analysis of over 5000 samples in about
      one month and proved to be reliable.

PMID- 23540768
TI  - Excessive fluctuations in knee joint moments during early stance in sprinting are
      caused by digital filtering procedures.
AB  - Inverse dynamics analyses are commonly used to understand movement patterns in
      all forms of gait. The aim of this study was to determine the effect of digital
      filtering procedures on the knee joint moments calculated during sprinting as an
      example of the possible influence of data analysis processes on interpretation of
      movement patterns. Data were obtained from three highly trained sprinters who
      completed a series of 30 m sprints. Ten different combinations of cut-off
      frequency were applied to the two-dimensional kinematic and kinetic input data
      with the kinetic cut-off frequency set equal to or higher than the kinematic cut
      off frequency. When using the commonly adopted practice of filtering the kinetic
      data with a higher cut-off frequency than the kinematic data, exaggerated
      fluctuations in the knee joint moment existed soon after contact. In extreme
      cases, the knee moved between flexor, extensor and flexor dominance in less than
      33 ms and through ranges exceeding 500 Nm. During an inverse dynamics analysis of
      locomotion, mismatched cut-off frequencies will likely affect the calculated
      joint moments if the cut-off frequency applied to the kinematic data is less than
      the true frequency content, particularly during impact phases. In the example of
      sprinting, exaggerated fluctuations in the knee joint moment appear to be data
      processing artefact rather than genuine characteristics of the joint kinetics.
      When the cut-off frequencies, and thus the frequency content of all input data,
      are matched, the fluctuations after contact are minimal and such a procedure is
      suggested for inverse dynamics analyses of gait.

PMID- 23540769
TI  - Technology use for health education to caregivers: an integrative review of
      nursing literature.
AB  - Providing caregivers with health education through educational technologies
      enhances safe care; and stimulates the decision process and communication among
      professionals, caregivers and patients. This article is an integrative review to
      identify what educational technologies have been used for health education to
      caregivers. The databases Web of Science, Bireme and Scopus were consulted. The
      inclusion criteria are as follows: full papers, published between 2001 and 2011,
      in English, Portuguese or Spanish. The descriptors used are the following:
      educational technology, health education and caregivers. Thirty-four papers were
      found, 27 of which were excluded because they did not comply with the inclusion
      criteria, resulting in a final sample of 7 papers. The results evidenced the use
      of light and hard technologies in health education for caregivers, aimed at the
      therapeutic discussion of care as well as telehealth service delivery. Research
      is needed which uses and assesses the use of hard educational technologies in
      health education for caregivers. 

PMID- 23540773
TI  - Enhanced electrogenerated chemiluminescence in thermoresponsive microgels.
AB  - The electrochemistry, photoluminescence and electrogenerated chemiluminescence of
      thermoresponsive redox microgels were investigated. For the first time,
      reversible ECL enhancement is demonstrated in stimuli-responsive 100-nm microgel
      particles. Such an unexpected amplification reached 2 orders of magnitude, and it
      is intrinsically correlated with the collapse of the microgel particles. The
      swell-collapse transition decreases the average distance between adjacent redox
      sites and favors the electron-transfer processes in the microgels resulting in
      the enhanced ECL emission.

PMID- 23540774
TI  - NMIBC risk calculators: how useful are they for the practicing urologist and how
      can their clinical utility be improved?
AB  - The natural history of non-muscle invasive bladder cancer (NMIBC) in individual
      patients can be unpredictable. Although there are known clinical and molecular
      factors associated with tumor recurrence and progression, it is challenging to
      reconcile these data during a typical patient encounter within a busy clinic. The
      authors discuss the European Organization for Research and Treatment of Cancer's
      risk tables along with other models for predicting prognosis in patients with
      NMIBC. The authors also describe their advantages and disadvantages and the
      barriers to using these risk models in daily clinical practice and provide a
      future perspective on prognostic models.

PMID- 23540775
TI  - Urinary markers/cytology: what and when should a urologist use.
AB  - As of 2012, bladder cancer is the fourth most common cancer afflicting men and
      ninth most common cancer in women. Nearly 80% of all bladder cancer diagnoses are
      non-muscle invasive at presentation, most of whom will develop recurrent disease
      within 5 years of initial diagnosis. Urinary tumor markers provide a noninvasive
      method for both screening and surveillance of bladder cancer. This article
      reviews the current Food and Drug Administration-approved urinary biomarkers for
      detection of non-muscle invasive bladder cancer.

PMID- 23540776
TI  - Office-based Bladder Tumor Fulguration and Surveillance: Indications and
      Techniques.
AB  - This article summarizes the current literature on office-based management of low
      grade, noninvasive bladder cancer. Discussion includes differences in recurrence
      and progression rates between neoplasm grades and stages, role of visual grading
      for diagnosis, cost advantages of treatment outside the operating room, and a
      step-by-step description of office-based procedures.

PMID- 23540777
TI  - Perioperative chemotherapy: when to use it, what to use, and why.
AB  - This article provides an overview of intravesical chemotherapy agents used for
      non-muscle invasive bladder cancer; summarizes the evidence on single-dose
      perioperative administration, induction therapy, and maintenance therapy; and
      briefly discusses ongoing research.

PMID- 23540778
TI  - Side effects of perioperative intravesical treatment and treatment strategies for
      these side effects.
AB  - Perioperative intravesical chemotherapy has a well-established role in the
      treatment of non-muscle invasive bladder cancer. There are multiple agents that
      can be used in this fashion with varying properties. Although chemical cystitis
      is the most common side effect and is usually self-limiting, significant toxicity
      can occur with intravesical chemotherapy. It is imperative that the urologist is
      aware of the acute and delayed side effects of intravesical chemotherapy and how
      to manage potential complications. Both local and systemic toxicities are
      discussed, as well as strategies to minimize and manage them.

PMID- 23540779
TI  - Strategies for optimizing bacillus Calmette-Guerin.
AB  - For treating patients with superficial bladder cancer and a moderate-to-high risk
      of tumor recurrence or progression, intravesical BCG has been the key development
      of the last generation. However, BCG has also brought with it a novel set of
      challenges. An understanding of when, to whom, and how BCG should be given is
      critical if optimal outcomes are to be achieved. This article the authors reviews
      the role that BCG has played in the management of bladder cancer over the last
      several decades and discusses specific approaches to optimize BCG. It focuses on
      selection and technical strategies.

PMID- 23540780
TI  - New agents for bacillus Calmette-Guerin-refractory bladder cancer.
AB  - Bacillus Calmette-Guerin has been established as the primary treatment of high
      risk non-muscle invasive bladder cancer. If patients do not respond or later
      recur, the most reliable treatment option is cystectomy. For those who are
      unwilling or unable to undergo this significant procedure, there is a multitude
      of alternative intravesical therapies. This article provides an overview of
      treatment options for patients with non-muscle invasive bladder cancer who have
      failed intravesical bacillus Calmette-Guerin therapy. It includes information on
      recent and ongoing trials and serves as a guide for clinicians regarding
      available therapies and a reference for researchers in this field.

PMID- 23540781
TI  - Determining the role of cystectomy for high-grade T1 urothelial carcinoma.
AB  - High-grade T1 (HGT1) urothelial carcinoma is an invasive disease with high
      predisposition for recurrence and progression. The optimal treatment of HGT1
      disease remains controversial. Clinical HGT1 disease represents a heterogeneous
      group of patients with variable clinical behavior. Radical cystectomy for HGT1
      disease is associated with excellent survival and offers the best opportunity for
      cure; however, it has a potential cost of decrease in quality of life. This
      article summarizes features associated with increased risk of progression and
      provides a framework for optimal treatment strategy with a focus on the role of
      radical cystectomy for HGT1 disease.

PMID- 23540782
TI  - The conundrum of prostatic urethral involvement.
AB  - The presence and depth of urothelial cancer involvement in the prostatic urethra
      can significantly affect the management of a patient with non-muscle invasive
      bladder cancer. This article presents an overview of the incidence, diagnosis,
      management, and follow-up of urothelial cancer.

PMID- 23540783
TI  - The costs of non-muscle invasive bladder cancer.
AB  - Bladder cancer is a common diagnosis, affecting 70,000 Americans each year.
      Because the diagnosis, management, and long-term follow-up of non-muscle invasive
      bladder cancer requires advanced imaging and invasive testing, economic
      evaluations have shown bladder cancer to be the costliest cancer to treat in the
      US on a per capita basis. Adjunctive tests for surveillance have not obviated the
      need for cystoscopy and cytology. Indirect costs to patients include loss of
      work, decreased productivity, and diminished quality of life associated with
      diagnosis, treatment, and surveillance. Improved value may be achieved with
      better compliance with evidence-based practices for non-muscle invasive bladder
      cancer care.

PMID- 23540784
TI  - New imaging techniques for non-muscle invasive bladder cancer: ready for
      primetime.
AB  - Treatment of non-muscle invasive bladder cancer (NMBIC) requires direct visual
      appreciation of the tumor. Transurethral resection that is dependent solely on
      white light cystoscopy (WLC) often fails to accurately stage or completely resect
      NMIBC. These deficiencies of WLC are significant contributors to the high rates
      of recurrence and eventual progression to muscle invasive disease. This article
      looks at technologies that are being used in adjunct to WLC to augment the
      urologist's ability to identify, stage, and treat NMIBC.

PMID- 23540785
TI  - Diagnostically challenging cases: what are atypia and dysplasia?
AB  - This article addresses the spectrum of atypia and dysplasia within the bladder
      epithelium and the diagnostic categories developed to further classify
      challenging lesions. In addition, the effects of inflammation, specific
      therapies, and instrumentation on the bladder mucosa as well as the associated
      difficulty in achieving the appropriate diagnosis are also discussed.

PMID- 23540786
TI  - Restaging transurethral resection for non-muscle invasive bladder cancer: who,
      why, when, and how?
AB  - The rate of clinical understaging in non-muscle invasive bladder cancer (NMIBC)
      after an initial transurethral resection (TUR) is significant, particularly for
      high-grade disease, and this has a major impact on prognosis. A repeat TUR, 2 to
      6 weeks following the initial resection, is recommended in appropriately selected
      cases to avoid diagnostic inaccuracy and improve treatment allocation. This
      article summarizes the rationale and indications for performing a repeat TUR in
      NMIBC and also provides information regarding patient selection and technique.

PMID- 23540787
TI  - Optimal risk-adapted surveillance strategies for NMIBC, including upper tract
      imaging.
AB  - Non-muscle invasive bladder cancer (NMIBC) represents approximately 70% of all
      incident cases of bladder cancer. The financial burden of NMIBC continues to
      increase, underscoring the importance of efficient, evidence-based management of
      this disease. Consensus guidelines differ on risk definition and in management
      recommendations. This article reviews the incidence and financial impact of NMIBC
      and details the recommendations for diagnosis, treatment, and surveillance made
      by the American Urological Association, International Consultation on Bladder
      Cancer-European Association of Urology, and National Comprehensive Cancer
      Network. Established and developing adjunctive laboratory and imaging tests
      directed at diagnosis and management of NMIBC are also discussed.

PMID- 23540788
TI  - Urologic Clinics of North America. Diagnosis, evaluation, and treatment of non
      muscle invasive bladder cancer. Foreword.

PMID- 23540789
TI  - Non-muscle invasive bladder cancer.

PMID- 23540790
TI  - Dimerized linear mimics of a natural cyclopeptide (TMC-95A) are potent
      noncovalent inhibitors of the eukaryotic 20S proteasome.
AB  - Noncovalent proteasome inhibitors introduce an alternative mechanism of
      inhibition to that of covalent inhibitors used in cancer therapy. Starting from a
      noncovalent linear mimic of TMC-95A, a series of dimerized inhibitors using
      polyaminohexanoic acid spacers has been designed and optimized to target
      simultaneously two of the six active sites of the eukaryotic 20S proteasome. The
      homodimerized compounds actively inhibited chymotrypsin-like (Ki = 6-11 nM) and
      trypsin-like activities, whereas postacid activity was poorly modified. The
      noncovalent binding mode was ascertained by X-ray crystallography of the
      inhibitors complexed with the yeast 20S proteasome. The inhibition of proteasomal
      activities in human cells was evaluated. The use of the multivalency inhibitor
      concept has produced highly efficient and selective noncovalent compounds (no
      inhibition of calpain and cathepsin) that have potential therapeutic advantages
      compared to covalent binders such as bortezomib and carfilzomib.

PMID- 23540791
TI  - Sexual and functional results after creation of a neovagina in women with Mayer
      Rokitansky-Kuster-Hauser syndrome: a comparison of nonsurgical and surgical
      procedures.
AB  - OBJECTIVE: To compare nonsurgical and surgical procedures for creation of a
      neovagina in women with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome in terms
      of sexual satisfaction. STUDY DESIGN: We report a cross-sectional study of 91
      women with MRKH syndrome undergoing a neovagina creation procedure. They were
      members of the French National Association of Women with MRKH syndrome. We
      analyzed all answers to a questionnaire mailed to each woman. The questionnaire
      solicited short answers concerning the diagnosis and the neovagina procedure, and
      included the standardized FSFI (Female Sexual Function Index) questionnaire. All
      analyses were performed using the chi-squared test and Student's t-test. A p
      value of <0.05 was considered statistically significant. RESULTS: Forty women
      answered the questionnaire. Twenty had been treated by Frank's method (non
      surgical group) and 20 had undergone a surgical procedure, sigmoid vaginoplasty
      (12 cases) or Davidov's technique (8 cases) (surgical group). The mean time after
      neovagina creation was 7 years (range 1-44 years). The population characteristics
      did not differ significantly between the nonsurgical and surgical groups. The
      total FSFI score indicated good and similar functional results in the two groups
      (25.3+/-7.5 versus 25.3+/-8.0). CONCLUSIONS: Functional sexual outcomes after
      nonsurgical and surgical methods were similar. Therefore, the Frank's method
      should be proposed as first line therapy because it is less invasive than
      surgical procedures. In the case of failure of this technique or of refusal by
      the patient, surgical reconstruction may then be offered.

PMID- 23540792
TI  - Retrospective analysis of prognostic variables and clinical outcomes in
      surgically staged intermediate risk endometrial carcinoma.
AB  - OBJECTIVE: To identify independent prognostic variables for surgically staged
      intermediate risk endometrial carcinoma as defined by the Gynecologic Oncology
      Group 99 (GOG99) criteria. STUDY DESIGN: Retrospective study of 239 patients with
      FIGO stage IB-occult IIB endometrioid type endometrial cancer, who were primarily
      treated with comprehensive staging surgery. Data were collected on
      clinicopathological variables, extent of primary surgery, postoperative adjuvant
      treatment, and patterns of recurrences. Kaplan-Meier survival curves were used to
      estimate disease free survival (DFS) and overall survival (OS), and multivariate
      Cox regression models were used to identify independent prognostic variables. The
      median follow-up time was 67 months (range, 12-183 months). RESULTS: The 5-year
      DFS and OS were 91.0% and 93.0%, respectively. On univariate Kaplan-Meier
      analysis, age>60 years, deep myometrial invasion (MI), presence of lymph vascular
      invasion (LVSI), and negative progesterone receptor (PR) status were
      significantly associated with diminished 5-year DFS and OS. The univariate
      analysis on patterns of failures demonstrated that patients with older age or
      positive LVSI were more inclined to develop locoregional recurrence, while PR
      status and the depth of MI had a statistically significant impact on distant
      failure. On multivariate analysis, PR status, age, and the depth of MI were
      independent prognostic variables for 5-year DFS, and age was the only independent
      prognostic variable for 5-year OS. LVSI and age were independent prognostic
      variables for locoregional recurrence, while PR status and depth of MI were
      independent prognostic variables for distant recurrence. CONCLUSIONS: Age, depth
      of MI, PR status and presence of LVSI are of independent prognostic value for
      intermediate risk endometrial cancer. The presence of these variables warrants
      consideration when deciding upon treatment strategies.

PMID- 23540793
TI  - Epidemiology and susceptibility of Gram-negative appendicitis pathogens: SMART
      2008-2010.
AB  - BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) has
      tracked the in vitro activity of ertapenem and comparators against aerobic gram
      negative bacteria from intra-abdominal infections since 2002. This report
      describes the epidemiology and susceptibility for clinical isolates associated
      with appendicitis, collected from 2008 to 2010. METHODS: A total of 1,720 gram
      negative bacilli were collected from patients with appendicitis in 122 hospitals
      in 39 countries worldwide; of these, 23% of isolates were from pediatric patients
      (<= 17 years old). Minimum inhibitory concentrations (MICs) and extended-spectrum
      beta-lactamase (ESBL) phenotypes were determined by broth microdilution and
      interpreted using Clinical and Laboratory Standards Institute guidelines.
      RESULTS: The global ESBL-positive rate was 16.3%, ranging from 2.2% for Proteus
      mirabilis to 16.6% for Escherichia coli and 20.1% for Klebsiella pneumoniae. The
      ESBL-positive rates differed by age group (17.7% in adults vs. 11.4% in children)
      and by geographic region, with significantly higher rates in Asia/Pacific (28.0%)
      and significantly lower rates in North America (9.1%), Africa/Middle East (4.8%),
      and Europe (4.4%). Amikacin, imipenem-cilastatin, piperacillin-tazobactam, and
      ertapenem were the most active of the tested agents against aerobic gram-negative
      appendicitis pathogens across pediatric and adult age groups and across
      geographic regions, including ESBL-positive isolates. Cefepime and ceftazidime
      were active against >= 90% of global pediatric isolates. E. coli, by far the most
      frequently isolated species (68% in adults and 75% in pediatric patients), was
      significantly less susceptible in adults than in pediatric patients (p<0.05;
      Fisher exact test) to all tested agents except amikacin, ertapenem, imipenem
      cilastatin, piperacillin-tazobactam, and ampicillin-sulbactam (with the latter
      showing low activity in both age groups). CONCLUSIONS: These in vitro data
      suggest that amikacin, imipenem-cilastatin, piperacillin-tazobactam, and
      ertapenem would perform well against aerobic gram-negative bacilli associated
      with appendicitis in both adults and children, especially in regions with high
      rates of ESBL-positive E. coli.

PMID- 23540794
TI  - The evaluation of iron overload through hepcidin level and its related factors in
      myelodysplastic syndromes.
AB  - We chose hepcidin and its related factors as evaluating indicators to determine
      the degrees of iron overload in myelodysplastic syndromes (MDS) patients. A total
      of 73 patients and 28 healthy volunteers were enrolled in this study. We
      performed enzyme-linked immunosorbent assay to measure both bone marrow and
      peripheral blood serum hepcidin. Real-time quantitative polymerase chain reaction
      was used to determine the gene expression of growth differentiation factor 15 and
      twisted gastrulation 1. Serum ferritin (SF), C-reactive protein (CRP), and
      erythropoietin were measured by routine standard laboratory assays. CD4(+) and
      CD19(+) lymphocytes and Th polarization were detected by flow cytometry. Twenty
      four MDS patients were measured their cardiac and liver iron deposition levels
      through magnetic resonance imaging (MRI) T2* examination. No significant
      difference was found between the bone marrow hepcidin levels and peripheral blood
      hepcidin levels (P = 0.134). Stratified according to different World Health
      Organization subtypes, refractory anemia with ringed sideroblasts patients had
      the lowest hepcidin levels (105.40 +/- 5.13 ng/ml), while refractory anemia with
      excess blasts-1 had the highest levels (335.71 +/- 25.16 ng/ml). Stratified
      according to International Prognostic Scoring System and WHO Classification-based
      Prognostic Scoring System, there was a significant difference of hepcidin levels
      between low-risk group and high-risk group in two systems, respectively (P =
      0.033 and 0.009). The hepcidin levels of CD4(+) high-expression group were
      demonstrated higher than the normal expression groups (P = 0.02), but the CD19(+)
      high-expression group did not show the same result (P = 0.206). Meanwhile,
      patients with a Th1 polarization trend had a high level of hepcidin versus normal
      group (P < 0.001). Liver iron concentration (LIC) measured by MRI T2* had a
      closer correlation (r = 0.582, P < 0.001) to hepcidin than serum ferritin, by
      stepwise regression. C-reactive protein and LIC seemed to be the key determinants
      of hepcidin, by multivariate regression. Inflammation plays an important role in
      the regulation of hepcidin expression. T-lymphocyte activation and Th
      polarization trend might participate in the regulatory mechanism partly. The
      capability of organ iron load assessment of MRI T2* seems better than that of SF.
      It seems that hepcidin with CRP and LIC measured by MRI T2* are potential
      indicators of iron overload in MDS patients. 

PMID- 23540795
TI  - Septic arthritis associated to gout and pseudogout: the importance of
      arthrocenthesis.

PMID- 23540797
TI  - Iridium porphyrins in CD3OD: reduction of Ir(III), CD3-OD bond cleavage, Ir-D
      acid dissociation and alkene reactions.
AB  - Methanol solutions of iridium(III) tetra(p-sulfonatophenyl)porphyrin
      [(TSPP)Ir(III)] form an equilibrium distribution of methanol and methoxide
      complexes ([(TSPP)Ir(III)(CD3OD)(2-n)(OCD3)n]((3+n)-)). Reaction of
      [(TSPP)Ir(III) with dihydrogen (D2) in methanol produces an iridium hydride
      [(TSPP)Ir(III)-D(CD3OD)](4-) in equilibrium with an iridium(I) complex
      ([(TSPP)Ir(I)(CD3OD)](5-)). The acid dissociation constant of the iridium hydride
      (Ir-D) in methanol at 298 K is 3.5 * 10(-12). The iridium(I) complex
      ([(TSPP)Ir(I)(CD3OD)](5-)) catalyzes reaction of [(TSPP)Ir(III)-D(CD3OD)](4-)
      with CD3-OD to produce an iridium methyl complex [(TSPP)Ir(III)-CD3(CD3OD)](4-)
      and D2O. Reactions of the iridium hydride with ethene and propene produce iridium
      alkyl complexes, but the Ir-D complex fails to give observable addition with
      acetaldehyde and carbon monoxide in methanol. Reaction of the iridium hydride
      with propene forms both the isopropyl and propyl complexes with free energy
      changes (DeltaG degrees  298 K) of -1.3 and -0.4 kcal mol(-1) respectively.
      Equilibrium thermodynamics and reactivity studies are used in discussing relative
      Ir-D, Ir-OCD3 and Ir-CD2- bond energetics in methanol.

PMID- 23540796
TI  - Coffee ring aptasensor for rapid protein detection.
AB  - We introduce a new biosensing platform for rapid protein detection that combines
      one of the simplest methods for biomolecular concentration, coffee ring
      formation, with a sensitive aptamer-based optical detection scheme. In this
      approach, aptamer beacons are utilized for signal transduction where a
      fluorescence signal is emitted in the presence of the target molecule. Signal
      amplification is achieved by concentrating aptamer-target complexes within liquid
      droplets, resulting in the formation of coffee ring "spots". Surfaces with
      various chemical coatings were utilized to investigate the correlation among
      surface hydrophobicity, concentration efficiency, and signal amplification. On
      the basis of our results, we found that the increase in the coffee ring diameter
      with larger droplet volumes is independent of surface hydrophobicity.
      Furthermore, we show that highly hydrophobic surfaces produce enhanced particle
      concentration via coffee ring formation, resulting in signal intensities 6-fold
      greater than those on hydrophilic surfaces. To validate this biosensing platform
      for the detection of clinical samples, we detected alpha-thrombin in human serum
      and 4-fold-diluted whole blood. Coffee ring spots from serum and blood produced
      detection signals up to 40 times larger than those from samples in liquid
      droplets. Additionally, this biosensor exhibits a lower limit of detection of 2
      ng/mL (54 pM) in serum, and 4 ng/mL (105 pM) in blood. On the basis of its
      simplicity and high performance, this platform demonstrates immense potential as
      an inexpensive diagnostic tool for the detection of disease biomarkers,
      particularly for use in developing countries that lack the resources and
      facilities required for conventional biodetection practices. 

PMID- 23540798
TI  - Theoretical insight for the metal insertion pathway of endohedral alkali metal
      fullerenes.
AB  - We have investigated the mechanism of alkali metal incorporation into C60
      fullerene by density functional theory (DFT) at the UB3LYP/6-31G* level of
      theory. Calculations were performed to study the insertion pathways of Li(+),
      Na(+), and K(+) through six- or five-membered rings of fullerene, and the
      computed energy barriers of metal ion insertion are compared with the available
      experimental data. Between the two possible insertion pathways, metal ion
      insertion through [2 + 2 + 2] ring opening of the six-membered ring is found to
      be more favored than the insertion through the ring opening of the five-membered
      ring. The size of the ring openings generated by the three metal ions is likely
      to be correlated with their ionic size, which shows the smallest opening for
      Li(+) and the largest for K(+) cation. The insertion energy barriers of the ions
      are found to be increased in the order of Li(+) < Na(+) < K(+) in line with the
      experimental results. The ring opening made by breaking of C-C bonds during the
      metal ion insertion in six- or five-membered rings can cause the ring to be
      rearranged and convert back into a closed fullerene cage to form a stable
      endohedral metal-fullerene complex.

PMID- 23540799
TI  - Identification of new and unusual rev and nef transcripts expressed by an HIV
      type 1 primary isolate.
AB  - We analyzed RNA splice site usage in three HIV-1 subtype B primary isolates
      through reverse transcriptase polymerase chain reaction (RT-PCR) amplification of
      spliced RNAs using a fluorescently labeled primer, with computerized size
      determination and quantification of PCR products, which were also identified by
      clone sequencing. In one isolate, P2149-3, unusual and unreported spliced
      transcripts were detected. This isolate preferentially used for rev RNA
      generation a 3' splice site (3'ss) located five nucleotides upstream of A4a,
      previously identified only in a T cell line-adapted virus and in a group O
      isolate, and designated A4d. P2149-3 also used an unreported 3'ss for rev RNA
      generation, designated A4h, located 20 nucleotides upstream of 3'ss A4c.
      Additionally, unusual nef RNAs using 3'ss A5a and A7a and with exon composition
      1.3.7 were identified. The identification of several unusual and unreported
      spliced transcripts in an HIV-1 primary isolate suggests a greater diversity of
      splice site usage in HIV-1 than previously appreciated.

PMID- 23540800
TI  - Drug-induced parkinsonism.
AB  - INTRODUCTION: Drug-induced parkinsonism (DIP) is the second most common cause of
      parkinsonism after idiopathic Parkinson's disease (iPD). Initially reported as a
      complication of antipsychotics, it was later recognized as a common complication
      of antidepressants, calcium channel antagonists, gastrointestinal prokinetics,
      antiepileptic drugs and many other compounds. Despite being a major health
      problem in certain populations, it seems to be frequently overlooked by the
      medical community. AREAS COVERED: This paper approaches the concept of DIP,
      reviews its epidemiology, clinical features and ancillary tests recommended for a
      correct diagnosis. The authors discuss the different drugs and its pathogenic
      mechanisms. The relevance of an early recognition and recommendations for a
      correct management are commented. EXPERT OPINION: Prescribers need to remain
      vigilant for DIP, particularly in the elderly, patients taking multiple drugs and
      those with genetic risk factors involved in iPD. Cessation of the causing agent
      is the main treatment and there is no evidence of benefit for the use of
      anticholinergics or levodopa. If the medication cannot be withdrawn, it should be
      switched to agents with a lower risk of DIP.

PMID- 23540801
TI  - Carotid endarterectomy improves peripheral but not central arterial stiffness.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) reduces the risk of cerebrovascular
      events due to the presence of atherosclerotic plaque in the internal carotid
      artery. Arterial stiffness is an indicator of cardiovascular risk and strongly
      associates with the development of atherosclerosis. This study aims to assess the
      short-term effect of CEA on arterial stiffness and haemodynamics. DESIGN:
      Prospective observational study. METHODS: Measurements of arterial stiffness and
      haemodynamics, including carotid-femoral pulse wave velocity (cfPWV), carotid
      radial PWV (crPWV), augmentation pressure, augmentation index, subendocardial
      viability ratio, central pressures and pulse pressure amplification, were
      performed pre- and 6 weeks post-CEA on both surgical and non-surgical sides.
      RESULTS: Fifty-nine patients completed the study (n = 46 men, age 68.9 +/- 10.1
      years). crPWV was decreased after CEA on the surgical (P = 0.01) and non-surgical
      side (P = 0.0008), AIx75 tended to decrease only on the surgical side (P = 0.06).
      cfPWV did not change significantly on either side. CONCLUSION: We assessed, for
      the first time, the short-term effect of CEA on arterial stiffness and
      haemodynamics. CEA improved peripheral but not central arterial stiffness. This
      study provides evidence for significant changes in certain arterial stiffness and
      haemodynamic parameters. Longer-term follow-up will assess whether these changes
      are sustained and whether CEA is associated with further haemodynamic benefits.

PMID- 23540802
TI  - Commentary regarding "A multicentric experience with open surgical repair and
      endovascular exclusion of popliteal artery aneurysms".

PMID- 23540803
TI  - Uptake of abdominal aortic aneurysm screening. A cohort study.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) are responsible for 1.4% of UK
      deaths. Deprivation is a risk factor for AAA. Screening reduces AAA related
      mortality and is cost effective if uptake remains high. The Highland aneurysm
      screening programme (HASP) began in 2001 offering screening to men in a sparsely
      populated area. The aim was to identify whether uptake varies with deprivation or
      rurality, in the context of an established programme. METHODS: Retrospective
      interrogation of HASP records was performed on all men offered screening from
      2001 until 2010. Deprivation and rurality status were derived from postcode of
      residence (SIMD'09 and URC'08) and the relationships with screening uptake were
      examined. RESULTS: Mean uptake over the decade was 90.1%. There was a strong
      association between deprivation and uptake, which ranged from 79.5% in the most
      deprived population to 97.5% in the least deprived (p < 0.001). The odds of men
      who were least deprived attending was 10.6 times higher than those who were most
      deprived (p < 0.001). Higher uptake was observed in more rural areas (p = 0.02).
      When combined in a logistic regression model, only deprivation remained
      significant, indicating any apparent effect of rurality was explained by
      deprivation. No change was observed in the mean aortic diameter of 65-year-old
      men or the incidence of AAA. CONCLUSION: HASP has a high uptake even in the most
      deprived and rural populations, demonstrating that programme design has overcome
      any potential rural disadvantage. A gradient of uptake associated with
      deprivation remains, although even the most deprived have an uptake of almost
      80%.

PMID- 23540804
TI  - Intra-peritoneal microdialysis and intra-abdominal pressure after endovascular
      repair of ruptured aortic aneurysms.
AB  - OBJECTIVES: This study aims to evaluate intra-peritoneal (ip) microdialysis after
      endovascular aortic repair (EVAR) of ruptured abdominal aortic aneurysm (rAAA) in
      patients developing intra-abdominal hypertension (IAH), requiring abdominal
      decompression. DESIGN: Prospective study. MATERIAL AND METHODS: A total of 16
      patients with rAAA treated with an emergency EVAR were followed up hourly for
      intra-abdominal pressure (IAP), urine production and ip lactate, pyruvate,
      glycerol and glucose by microdialysis, analysed only at the end of the study.
      Abdominal decompression was performed on clinical criteria, and decompressed (D)
      and non-decompressed (ND) patients were compared. RESULTS: The ip
      lactate/pyruvate (l/p) ratio was higher in the D group than in the ND group
      during the first five postoperative hours (mean 20 vs. 12), p = 0.005 and at 1 h
      prior to decompression compared to the fifth hour in the ND group (24 vs. 13), p
      = 0.016. Glycerol levels were higher in the D group during the first
      postoperative hours (mean 274.6 vs. 121.7 MUM), p = 0.022. The IAP was higher
      only at 1 h prior to decompression in the D group compared to the ND group at the
      fifth hour (mean 19 vs. 14 mmHg). CONCLUSIONS: Ip l/p ratio and glycerol levels
      are elevated immediately postoperatively in patients developing IAH leading to
      organ failure and subsequent abdominal decompression.

PMID- 23540805
TI  - Response to the letter: Lejay A, Thaveau F, Georg Y, Bajcz C, Kretz JG, Chakfe N.
      Autonomy following revascularisation in 80-year-old patients with critical limb
      ischemia. Eur J Vasc Endovasc Surg 2012;44:562-7.

PMID- 23540806
TI  - The single-centre experience of the supra-arch chimney technique in endovascular
      repair of type B aortic dissections.
AB  - OBJECTIVES: We summarised the data performed at our centre to evaluate the
      feasibility of the chimney technique in type B aortic dissections (ADs) with
      supra-aortic vessel involvement. METHODS: From September 2006 to December 2011,
      34 thoracic endovascular aortic repairs (TEVARs) for ADs were performed combined
      with reconstruction of the arch branches with chimney stents (innominate artery,
      IA, n = 3; left common carotid artery, LCCA, n = 8; left subclavian artery, LSA,
      n = 23). Indications for these chimney stents included an inadequate proximal
      landing zone (<1.5 cm); high surgical-risk patients who are not suitable for open
      repair or hybrid procedures; and emergent endovascular repair of ADs. The series
      consisted of 13 acute, 12 sub-acute and 9 chronic cases. The right common carotid
      left common carotid-left subclavian artery bypasses were performed in the IA
      chimney cases to reserve an adequate cerebral perfusion from the LCCA and left
      vertebral artery, while the left common carotid-left subclavian artery bypasses
      were performed in the cases having dominant left vertebral arteries. All the
      TEVARs, chimney stents and bypasses were performed as a single stage. Follow-ups
      were performed at 3, 6 and 12 months, and yearly thereafter. RESULTS: Endografts
      were deployed in Zone 0 (n = 3, 9%), Zone 1 (n = 8, 24%) and Zone 2 (n = 23,
      67%). Twenty-five (74%) balloon-expandable and 9 (26%) self-expanding stents were
      used, of which seven (21%) were covered and 27 (79%) were bare stents. The
      technical success rate was 82% (28/34). Immediate type I endoleaks were observed
      in five patients (5/34, 15%), all of which underwent bare chimney-stent repairs.
      Three self-expanding chimney stents were compressed by endografts and another
      balloon expandable stent was deployed inside the first one. Five patients
      underwent surgical bypasses (RCCA-LCCA-LSA, n = 3; LCCA-LSA, n = 2).
      Perioperative morbidity included one ST-elevation myocardial infarction. No
      perioperative death or stroke was observed. The mean follow-up was 16.3 months
      (range, 3-60 months). Primary patency was maintained in all the chimney stents as
      well as the surgical bypasses. No stent fracture or recurrent chimney-related
      endoleak was observed during the follow-up period. CONCLUSIONS: In repairs for
      type B ADs, the chimney technique provides a minimally invasive way of preserving
      flow to the arch branches combined with a favourable mid-term outcome. The bare
      stents seemed to be related to a higher probability of the immediate type I
      endoleaks. A balloon-expandable stent should be regarded as the first choice due
      to its greater radial strength.

PMID- 23540807
TI  - Evidence-based management of PAD & the diabetic foot.
AB  - Diabetic foot ulceration (DFU) is associated with high morbidity and mortality,
      and represents the leading cause of hospitalization in patients with diabetes.
      Peripheral arterial disease (PAD), present in half of patients with DFU, is an
      independent predictor of limb loss and can be difficult to diagnose in a diabetic
      population. This review focuses on the evidence for therapeutic strategies in the
      management of patients with DFU. We highlight the importance of timely referral
      of patients presenting with a new foot ulcer to a multidisciplinary team, which
      includes vascular surgeons and interventional radiologists.

PMID- 23540808
TI  - Endovascular treatment of aorto-iliac aneurysms: four-year results of iliac
      branch endograft.
AB  - INTRODUCTION: The aim of this report was to analyse early and mid-term outcomes
      of endovascular treatment (endovascular aneurysm repair, EVAR) for aorto-iliac
      aneurysms with the use of an iliac branch device (IBD). REPORT: A total of 85
      EVAR procedures with IBD were electively carried out in 81 patients between
      September 2007 and August 2012. Technical success was obtained in 98.7% of the
      cases. The mean follow-up duration was 20.4 months (SD +/- 15.4). There was one
      IBD occlusion (1.2%). Estimated 48 months' survival, freedom from re-intervention
      and branch occlusion were 76.7%, 88.3% and 98%, respectively. CONCLUSIONS: EVAR
      for aorto-iliac aneurysms using IBD is an effective procedure with low
      complication and re-intervention rates at mid-term follow-up.

PMID- 23540809
TI  - Brachiobasilic fistula formation - single versus two stage procedure.
AB  - BACKGROUND: Brachial basilic (BB) fistulae are a form of vascular access for
      patients requiring dialysis. They are indicated when the cephalic vein is
      unsuitable for use. This fistula can be created with either a single stage or a
      two stage procedure. We aimed to compare the two techniques. METHODS: 73 BB
      fistulae (29 single and 44 two-stage) were created over a 5-year period (2003
      2008). Data including sex, age, dialysis and diabetic status was collected from
      the case notes. Patency and time to maturity data was collected prospectively on
      an electronic database within the dialysis unit. RESULTS: There was no
      significant difference in functional patency rates between the two methods. A
      significant difference was identified between patients who had their fistula
      created prior to starting dialysis compared to those who had their fistula
      created after starting dialysis, in both initial patency rate (p = 0.017) and
      long term survival of the fistulae (p = 0.002). CONCLUSION: We identified no
      significant difference of patency between the two methods. This implies that a
      single stage procedure has benefits, by offering a quicker form of vascular
      access. Patients who had their fistulae created prior to dialysis had improved
      patency rates.

PMID- 23540810
TI  - 6:2 Fluorotelomer alcohol aerobic biotransformation in activated sludge from two
      domestic wastewater treatment plants.
AB  - 6:2 Fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] is a major basic chemical
      being used to manufacture FTOH-based products. After the end of use, 6:2 FTOH
      based products may be released to domestic wastewater treatment plants (WWTPs) as
      a first major environmental entry point. Activated sludge collected from two
      WWTPs was dosed with 6:2 FTOH to investigate its biotransformation rate and to
      identify major transformation products. The volatile 5:2 sFTOH [F(CF2)5CH(OH)CH3]
      is the most abundant transformation product and accounted for an average of
      40mol% of initially dosed 6:2 FTOH after two months of incubation with activated
      sludge, with 30mol% detected in the headspace. PFPeA [F(CF2)4COOH] averaged
      4.4mol% after two months, 2.4-7 times lower than that in sediment and soils. The
      much lower level of PFPeA formed in activated sludge compared with soil indicates
      that microbial populations in activated sludge may lack enzymes or suitable
      environment conditions to promote rapid 5:2 sFTOH decarboxylation to form PFPeA,
      resulting in more 5:2 sFTOH partitioned to the headspace. PFHxA [F(CF2)5COOH] and
      5:3 [F(CF2)5CH2CH2COOH] acid are major non-volatile transformation products in
      activated sludge. For example, PFHxA averaged 11mol% after two months, which is
      about 30% higher compared with sediment and soils, suggesting that microbes in
      WWTPs may utilize similar pathways as that in sediment and soils to convert 5:2
      sFTOH to PFHxA. 5:3 Acid averaged 14mol% after two months, comparable to that in
      soils and slightly lower than in sediment, further confirming that 5:3 acid is a
      unique product of 6:2 FTOH biotransformation in the environment.

PMID- 23540811
TI  - Removal of diclofenac by conventional drinking water treatment processes and
      granular activated carbon filtration.
AB  - This study was carried out to evaluate the efficiency of conventional drinking
      water treatment processes with and without pre-oxidation with chlorine and
      chlorine dioxide and the use of granular activated carbon (GAC) filtration for
      the removal of diclofenac (DCF). Water treatment was performed using the Jar test
      with filters on a lab scale, employing nonchlorinated artesian well water
      prepared with aquatic humic substances to yield 20HU true color, kaolin turbidity
      of 70 NTU and 1mgL(-1) DCF. For the quantification of DCF in water samples, solid
      phase extraction and HPLC-DAD methods were developed and validated. There was no
      removal of DCF in coagulation with aluminum sulfate (3.47mgAlL(-1) and pH=6.5),
      flocculation, sedimentation and sand filtration. In the treatment with pre
      oxidation and disinfection, DCF was partially removed, but the concentration of
      dissolved organic carbon (DOC) was unchanged and byproducts of DCF were observed.
      Chlorine dioxide was more effective than chorine in oxidizing DCF. In conclusion,
      the identification of DCF and DOC in finished water indicated the incomplete
      elimination of DCF through conventional treatments. Nevertheless, conventional
      drinking water treatment followed by GAC filtration was effective in removing DCF
      (?99.7%). In the oxidation with chlorine, three byproducts were tentatively
      identified, corresponding to a hydroxylation, aromatic substitution of one
      hydrogen by chlorine and a decarboxylation/hydroxylation. Oxidation with chlorine
      dioxide resulted in only one byproduct (hydroxylation).

PMID- 23540812
TI  - H3PW12O40/TiO2 catalyst-induced photodegradation of bisphenol A (BPA): kinetics,
      toxicity and degradation pathways.
AB  - A series of experiments were conducted to investigate the kinetics of bisphenol A
      (2,2-bis(4-hydroxyphenyl)propane, BPA) degradation using H3PW12O40/TiO2
      (PW12/TiO2) composite catalyst, toxicity of BPA intermediate products and
      degradation pathways. The results showed that the BPA photodegradation using
      PW12/TiO2 catalyst followed the first-order kinetics, and under the optimal
      experimental conditions at H3PW12O40 loading amount of 6.3%, BPA initial
      concentration of 5 mg L(-1), and the solution pH of 8.2, the kinetic constant was
      3.7-fold larger than that of pristine TiO2. The hydroxyl radicals derived from
      the electroreduction of dissolved oxygen with electrons via chain reactions was
      the main reactive oxygen species. According to the identified intermediates, 4
      isopropanolphenol, hydroquinone, 4-hydroxybenzoic acid, and phenol, the possible
      BPA photodegradation pathways were proposed. Upon 12h irradiation, 77% BPA (20 mg
      L(-1)) was mineralized and the toxicity to Daphnia magna (D. magna) was almost
      disappeared, implying the strong oxidation ability of PW12/TiO2 catalyst. The
      studies provide important information about the BPA degradation and promote the
      technical development for BPA removal.

PMID- 23540813
TI  - Surface engineering of ultrafine cellulose nanofibrils toward polymer
      nanocomposite materials.
AB  - Surface grafting of crystalline and ultrafine cellulose nanofibrils with
      poly(ethylene glycol) (PEG) chains via ionic bonds was achieved by a simple ion
      exchange treatment. The PEG-grafted cellulose nanofibrils exhibited
      nanodispersibility in organic solvents such as chloroform, toluene, and
      tetrahydrofuran. Then, the PEG-grafted cellulose nanofibril/chloroform dispersion
      and poly(L-lactide) (PLLA)/chloroform solution were mixed, and the PEG-grafted
      cellulose nanofibril/PLLA composite films with various blend ratios were prepared
      by casting the mixtures on a plate and drying. The tensile strength, Young's
      modulus, and work of fracture of the composite films were remarkably improved,
      despite low cellulose addition levels (<1 wt %). The highly efficient
      nanocomposite effect was explained in terms of achievement of nanodispersion
      states of the PEG-grafted cellulose nanofibrils in the PLLA matrix. Moreover,
      some attractive interactions mediated by the PEG chains were likely to be formed
      between the cellulose nanofibrils and PLLA molecules in the composites,
      additionally enhancing the efficient nanocomposite effect.

PMID- 23540814
TI  - A tissue engineering strategy for the treatment of avascular necrosis of the
      femoral head.
AB  - BACKGROUND & PURPOSE: Skeletal stem cells (SSCs) and impaction bone grafting
      (IBG) can be combined to produce a mechanically stable living bone composite.
      This novel strategy has been translated to the treatment of avascular necrosis of
      the femoral head. Surgical technique, clinical follow-up and retrieval analysis
      data of this translational case series is presented. METHODS: SSCs and milled
      allograft were impacted into necrotic bone in five femoral heads of four
      patients. Cell viability was confirmed by parallel in vitro culture of the cell
      graft constructs. Patient follow-up was by serial clinical and radiological
      examination. Tissue engineered bone was retrieved from two retrieved femoral
      heads and was analysed by histology, microcomputed tomography (MUCT) and
      mechanical testing. RESULTS: Three patients remain asymptomatic at 22- to 44
      month follow-up. One patient (both hips) required total hip replacement due to
      widespread residual necrosis. Retrieved tissue engineered bone demonstrated a
      mature trabecular micro-architecture histologically and on MUCT. Bone density and
      axial compression strength were comparable to trabecular bone. CONCLUSIONS:
      Clinical follow-up shows this to be an effective new treatment for focal early
      stage avascular necrosis of the femoral head. Unique retrieval analysis of
      clinically translated tissue engineered bone has demonstrated regeneration of
      tissue that is both structurally and functionally analogous to normal trabecular
      bone.

PMID- 23540815
TI  - A 9-state analysis of designer stimulant, "bath salt," hospital visits reported
      to poison control centers.
AB  - STUDY OBJECTIVE: A new generation of designer stimulants marketed as "bath salts"
      emerged in late 2010. The goal is to describe the epidemiologic emergence of
      designer stimulants in 9 states in the Midwest. METHODS: A retrospective review
      of the National Poison Data System was performed between November 1, 2010, and
      November 30, 2011. Inclusion criteria were health care-evaluated bath salts or
      other synthetic stimulants exposures. Cases were excluded if the exposure was
      unrelated to a designer stimulant. Demographic and clinical characteristics of
      cases were calculated and differences in outcome and exposure by generation were
      examined. RESULTS: One thousand six hundred thirty-three patients met the
      inclusion criteria. Age ranged from 1 day to 61 years (mean=29.2 years), with
      67.9% male patients. The most common clinical features were agitation (62.2%),
      tachycardia (55.2%), and hallucinations (32.7%). In addition to 15.5% of patients
      having a major medical effect, 0.6% died. Reason for use was primarily
      intentional abuse (88.5%). However, 0.7% of patients reported withdrawal.
      Treatment involved primarily benzodiazepines (58.5%), with 8.7% of patients being
      intubated. Baby Boomers were more likely to have a major medical outcome (24.2%)
      and to report injection as the method of administration (8.6%-12.9%). CONCLUSION:
      Synthetic stimulants rapidly swept across the Midwest, resulting in more than
      1,600 patients seeking medical care. Serious medical effects or death was
      observed in 16.1% of cases. Older generations were more likely to inject and to
      have a major medical outcome.

PMID- 23540817
TI  - Quality from a different viewpoint.

PMID- 23540818
TI  - Is a patient's type of substance dependence (alcohol, drug or both) associated
      with the quality of primary care they receive?
AB  - BACKGROUND: Primary care clinicians' attitudes may differ based on patients'
      substance dependence type (alcohol, other drugs or both). AIM: The aim of this
      study was to evaluate whether substance dependence type is associated with
      primary care quality (PCQ). METHODS: We tested the association between substance
      dependence type and six PCQ scales of the Primary Care Assessment Survey (PCAS)
      in multivariable linear regression models. We studied alcohol- and/or drug
      dependent patients followed prospectively who reported having a PCC ( n = 427) in
      a primary care setting. RESULTS: We used the Composite International Diagnostic
      Interview-Short Form to assess substance dependence type and we used the PCAS
      questionnaire to measure primary care quality. Dependence type was significantly
      associated with PCQ for all PCAS scales except whole-person knowledge. For the
      significant associations, subjects with drug dependence (alone or together with
      alcohol) had lower observed PCAS scores compared with those with alcohol
      dependence only, except for preventive counselling. CONCLUSIONS: Drug dependence
      was associated with worse PCQ for most domains. Understanding the reasons for
      these differences and addressing them may help improve the quality of primary
      care for patients with addictions.

PMID- 23540820
TI  - Screening for peripheral vascular disease in patients with type 2 diabetes in
      Malta in a primary care setting.
AB  - BACKGROUND: Peripheral vascular disease (PVD) is strongly associated with type 2
      diabetes. PVD assessment and diagnosis are often neglected in primary care office
      visits, and ankle/brachial pressure index (ABPI) examinations are seldom
      performed for PVD detection. The purpose of this study was to evaluate the
      occurrence of PVD in a primary care setting using ABPI in patients with type 2
      diabetes in Malta. METHOD: A retrospective study was conducted on a cohort of 243
      patients with type 2 diabetes to address various issues. As part of this large
      study, data from ABPI measurements collected using a portable hand-held Doppler
      with ankle pressures of <0.8 suggestive of PVD were extracted. RESULTS: Twenty
      six per cent of the sample had to be referred for further vascular assessment
      following this screening programme due to their critical vascular status.
      Furthermore, at the time of examination, approximately 7% of the patients had an
      ABPI of less than 0.8 in both left and right extremities. CONCLUSION: A
      significant proportion of Maltese patients with type 2 diabetes who visit primary
      care present with vascular insufficiency. The use of ABPI should be considered as
      an added measurement in order to facilitate early detection and treatment and
      reduce the burden of PVD in this high-risk population.

PMID- 23540819
TI  - Association between statin use and lipid status in quality improvement
      initiatives: statin use, a potential surrogate?
AB  - OBJECTIVE: To test the association between statin use and low-density-lipoprotein
      (LDL)-cholesterol control in outpatient community practices undergoing quality
      improvement efforts in diabetes care. DESIGN: A retrospective observational study
      of primary care practices that underwent efforts at improving the quality of
      diabetes care. Each practice provided an electronic registry-based monthly report
      of the percentage of patients with LDL <130 mg/dl (3.4 mmol/l), LDL <100 mg/dl
      (2.6 mmol/l) and statin use. SETTING: Primary care practices in Pennsylvania
      focused on improving diabetes care by implementing the Chronic Care Model in
      urban, suburban and rural regions. PARTICIPANTS: Consisted of 109 primary care
      practices, academic practices and federal health centres. Practices typically saw
      patients from a mix of government-funded and commercial health plan carriers.
      RESULTS: There was a positive linear association between documented statin use
      and the percentage of patients with LDL <130 mg/dl (3.4 mmol/l) and LDL <100
      mg/dl (2.6 mmol/l = goal for patients with diabetes). The correlation between
      statin use and LDL <130 was 0.50 (95% CI 0.41-0.64), and between statin use and
      the percentage of patients with LDL <100 was 0.47 (95% CI 0.29-0.58). Practices
      with 5% larger statin use had an expected 1.9% larger percentage of patients with
      LDL <130 (95% CI 1.4 -2.9%) and an expected 1.7% larger percentage of patients
      with LDL <100 (95% CI 0.9- 2.3%). CONCLUSION: An association exists between
      statin use and LDL control in the real world of primary care practices undergoing
      quality improvement. Additional studies are necessary to ultimately test the
      validity of statin use as a process measure and/or surrogate for LDL-cholesterol
      control.

PMID- 23540821
TI  - Proactive primary care of carers of people with cognitive impairment: a
      feasibility study.
AB  - BACKGROUND: Over 250 000 Australians live with dementia, and it is estimated that
      this number will more than double by 2030. Many people with dementia or cognitive
      impairment are cared for at home by family carers who may themselves be frail
      older adults or who may suffer from chronic conditions. There is evidence that
      caring has adverse impacts on carers; however, many do not seek or delay seeking
      appropriate health care. AIM: To explore the feasibility of a protocol to
      identify the unmet healthcare needs of carers of people with cognitive
      impairment. METHOD: This feasibility study used a mixed-methods approach. Data
      were collected through a set of three wellbeing questionnaires, and interviews
      with carers and one general practitioner. Carers were recruited through
      government-funded adult day care centres in Perth, Western Australia. General
      practitioners were nominated by the carers. The sample included 15 carers and one
      general practitioner. RESULTS: Carer participants in this study experienced
      varying degrees of care burden. Insomnia, fatigue and pain were the most
      prominent symptoms. Their overall health status was lower than that of the
      general population, with physical functioning and bodily pain obtaining the
      lowest scores. Carers found the protocol useful and the questionnaires easy to
      complete; they reported specific outcomes resulting from the implementation of
      the protocol aimed at addressing their healthcare needs. CONCLUSION: The study
      results demonstrate the feasibility of adopting a protocol to identify and
      address carers' unmet healthcare issues, and warrant further research. In the
      context of an ageing population, the growing number of carers of people with
      cognitive impairment and dementia need to receive adequate support to enable them
      to continue to provide care.

PMID- 23540822
TI  - Comprehensive assessment of chronic pain management in primary care: a first
      phase of a quality improvement initiative at a multisite Community Health Center.
AB  - BACKGROUND: The objective of this study was to conduct a comprehensive formative
      assessment of chronic pain management in a large, multisite community health
      centre and use the results to design a quality improvement initiative based on an
      evidence-based practice model developed by the Veterans Health Administration.
      Improving quality and safety by incorporating evidence-based practices (EBP) is
      challenging, particularly in busy clinical practices such as Federally Qualified
      Health Centers (FQHCs). FQHCs grapple with financial constraints, lack of
      resources and complex patient populations. METHODS: The Promoting Action on
      Research Implementation in Health Services (PARIHS) Framework served as a basis
      for the comprehensive assessment. We used a range of measures and tools to
      examine pain care from a variety of perspectives. Patients with chronic pain were
      identified using self-reported pain scores and opioid prescription records. We
      employed multiple data collection strategies, including querying our electronic
      health records system, manual chart reviews and staff surveys. RESULTS: We found
      that patients with chronic pain had extremely high primary care utilisation rates
      while referral rates to pain-related specialties were low for these patients.
      Large gaps existed in primary care provider adherence to standards for pain care
      documentation and practice. There was wide provider variability in the
      prescription of opioids to treat pain. Staff surveys found substantial variation
      in both pain care knowledge and readiness to change, as well as low confidence in
      providers' ability to manage pain, and dissatisfaction with the resources
      available to support chronic pain care. CONCLUSIONS: Improving chronic pain
      management at this Community Health Center requires a multifaceted intervention
      aimed at addressing many of the problems identified during the assessment phase.
      During the intervention we will put a greater emphasis on increasing options for
      behavioural health and complementary medicine support, increasing access to
      specialty consultation, providing pain-specific CME for providers, and improving
      documentation of pain care in the electronic health records.

PMID- 23540823
TI  - Improving the quality of primary care.
AB  - BACKGROUND: This paper considers the role of teaching primary care trusts (tPCTs)
      at the turn of the century. A retrospective evaluation of a complex intervention
      is used. The evaluation has three perspectives. These are (1) a commentary on
      tPCTs in health policy in England, (2) the authors' reflections as senior members
      of a tPCT in Northern England and (3) a look-back exercise with tPCT members.
      RESULTS: It outlines the achievements and reflects on the experience of the tPCT
      and its relationship with its stakeholders. The resultant themes and challenges
      experienced by the tPCT members working at their organisational boundaries with
      their stakeholder both provide organisational developmental insight for the
      emergent primary care commissioning groups (Health and Social Care Bill 2011) and
      highlight the continuing need for organisational cultural change within general
      practice. CONCLUSION: Quality criteria for acceptability, accessibility,
      appropriateness, equity, clinical effectiveness and cost-effectiveness can only
      be truly addressed by a learning organisation approach. This was one of the
      original remits for tPCTs.

PMID- 23540824
TI  - Primary care attitudes to methotrexate monitoring.
AB  - BACKGROUND: Rheumatoid arthritis affects 1% of the UK population. First-line
      treatment is with the immunosuppressant, methotrexate (MTX). This is generally
      regarded as a safe and effective medication when taken at the right dose, with
      appropriate monitoring. Very occasionally it causes serious harm or death. In
      2006, the National Patient Safety Agency issued a safety alert following
      increasing reports of prescribing errors and toxicity. Over the last decade,
      Northwick Park Hospital has seen two MTX-related deaths and other morbidity.
      Repeat prescriptions and monitoring are generally undertaken in primary care,
      although concerns have been raised about variation in local practice. Poor
      communication and inadequate monitoring are safety concerns. Duplication of
      monitoring has cost implications. Local (hospital Shared Care Guidelines (SCG) )
      and national guidelines, from the British Society of Rheumatology (BSR), on MTX
      monitoring are freely available and accessible. METHOD: We surveyed our local GP
      community to better understand their practice and establish where patient care
      could be improved. RESULTS: We contacted 86 practices, of which 31 replied (a
      response rate of 36%). On average, there was one patient on MTX per 743 in the
      practice (0.13%), ranging from 0-0.5%. All GPs admitted they repeated MTX
      prescriptions, but only 77.4% monitored these. Of those who did monitor, 58.6%
      were aware of local guidelines and only 48.4% were aware of national guidelines.
      A total of 26.7% of GPs were monitoring and prescribing MTX but not aware of any
      guidelines. Among this number, 37.5% did not feel they needed further education.
      CONCLUSION: Serious safety concerns have been raised, including the poor response
      rate. Any doctor prescribing MTX should also be monitoring according to
      guidelines. Low numbers of patients on MTX per practice are surprising, possibly
      reflecting inadequate records or under-diagnosis. With these data, we have
      encouraged commissioners to fund a computer monitoring system accessible to
      primary and secondary care for improved patient safety, and to ultimately save
      costs by reducing duplication of work.

PMID- 23540825
TI  - Temperature effects on alkaline earth metal ions adsorption on gibbsite:
      approaches from macroscopic sorption experiments and molecular dynamics
      simulations.
AB  - Two approaches, macroscopic adsorption experiments and molecular dynamics
      simulations, were employed to study the effect of temperature on alkaline earth
      metals adsorption on gibbsite surfaces. Increased reaction temperature enhanced
      the extent of metal ion adsorption for all of the alkaline earth metals studied.
      Whereas Mg(2+) and Sr(2+) adsorption displayed dependence on ionic strength,
      Sr(2+) adsorption exhibited less dependence on background ionic strength
      regardless of temperature. The ionic strength dependence was attributed to outer
      sphere complexation reactions. The ionic strength effect on metal ion removal
      decreased with increasing temperature for both metals. Ba(2+) removal by
      gibbsite, on the other hand, was not affected by ionic strength. Results from
      molecular dynamics simulations were in agreement with the findings of the
      experimental study. The amount of thermal energy required to remove waters of
      hydration from the metal cation and the ratio of outer-sphere to inner-sphere
      complexation decreased with increasing ionic radii. It was observed from both
      macroscopic and molecular approaches that the tendency to form inner-sphere
      complexes on gibbsite decreased in the order: Ba(2+)>Sr(2+)>Mg(2+) and that the
      common assumption that alkaline earth metal ions form outer-sphere complexes
      appears to be dependent on ionic radius and temperature.

PMID- 23540826
TI  - Designed synthesis and supramolecular architectures of furan-substituted perylene
      diimide.
AB  - Novel furan-substituted perylene diimides are successfully synthesized and an
      efficient supramolecular architecture approach to construct zero/one-dimensional
      nano- and micro-structures by controlling solvents has been demonstrated. The
      aggregate structure conversion in different molecular structures can be
      controlled in the form of sphere-like, rod-like, and vesicle-like structures. As
      expected, these solid supramolecular rod-like architectures displayed interesting
      optical waveguide behavior, which indicates the aggregate structure materials of
      furan-substituted perylene diimides have the potential application as micro-scale
      photonic elements.

PMID- 23540827
TI  - Exploring the pH dependent SERS spectra of 2-mercaptoimidazole molecule adsorbed
      on silver nanocolloids in the light of Albrecht's "A" term and Herzberg-Teller
      charge transfer contribution.
AB  - The pH dependent surface-enhanced Raman scattering (SERS) spectra of biologically
      and industrially significant, 2-mercaptoimidazole (2-MI) molecule at 1.0*10(-10)M
      concentration have been investigated. The pH dependent SERS spectra are compared
      with the corresponding normal Raman spectra (NRS) of the molecule. The
      vibrational analyses of the pH dependent NRS spectra of the molecule reveal that
      in the acidic pH medium, the cationic form of the molecule is preponderant, while
      in the neutral pH, the existence of the cationic, normal, ylidic, and anionic
      forms of the molecule are all prevalent. However, in the alkaline pH medium, the
      anionic form of the molecule is estimated to be dominant. The SERS spectral
      analyses suggest the predominant adsorption of the cationic and the normal forms
      of the molecule on the nanocolloidal silver surface at acidic pH of the medium.
      However, at neutral pH, the cationic and/or normal, ylidic forms of the molecule
      take active part in the adsorption process, while considerable interactions of
      the normal, ylidic and/or anionic forms of the molecule with the nanocolloidal
      silver surface are presaged at alkaline pH of the medium. The genesis of
      selective enhancements of the Raman bands in the SERS spectra of the molecule
      recorded at various pH values of the medium has been unveiled from the view of
      the Albretcht's "A" and Herzberg-Teller (HT) charge transfer (CT) contribution.

PMID- 23540828
TI  - Constructional details of polystyrene-block-poly(4-vinylpyridine) ordered thin
      film morphology.
AB  - One of the most important issues for spin-coated diblock copolymer thin films is
      to distinguish the blocks by common techniques, especially for the diblock
      copolymers containing one block could form active domain. Aiming different
      estimations on the composition of surface microdomains in polystyrene-block-poly
      (4-vinylpyridine) (PS-b-P4VP) atomic force microscope (AFM) phase images, AFM,
      transmission electron microscopy, and droplet shape analyzer were used to
      identify the constructional details of the polymer thin film morphology. It was
      confirmed that PS block is harder than P4VP block in symmetric PS-b-P4VP films
      and corresponds to brighter regions in AFM phase image. It is helpful to
      distinguish the nanodomains that originate from the different blocks in PS-b-P4VP
      thin films. The structure evolutions of PS-b-P4VP film annealed with different
      selective solvents were studied and discussed. The results indicated that the
      core-corona inversion process is due to the cores of micelles swell and coalesce
      together rather than local reorganization of the chains.

PMID- 23540829
TI  - Metallosupramolecular thin films using a tritopic cyclam-based ligand.
AB  - We present the preparation and characterization of novel metallosupramolecular
      thin films on solid substrates. These films incorporate metallosupramolecular
      polymers based on a tritopic cyclam bis-terpyridine ligand and are formed using
      different deposition techniques. From layer-by-layer (LBL) method, alternate thin
      multilayers of this metallosupramolecule along with oppositely charged
      polyelectrolyte are constructed by electrostatic self-assembly. Using dip-coating
      method, homogenous monolayers are deposited. The monolayer thickness is
      controlled by withdraw velocity of substrate. In a direct-assembly approach:
      Langmuir-Blodgett (LB), well-ordered metallosupramolecular monolayer is achieved
      by using a Metallosupramolecular Polyelectrolyte Amphiphile Complex (MPAC). The
      structures of these metallosupramolecular thin films are characterized by X-ray
      reflectivity (XRR), Atomic Force Microscopy (AFM), Langmuir isotherms, and UV/Vis
      absorption. The results open access to fabricate novel molecular materials such
      as sensors and memory devices.

PMID- 23540830
TI  - Fleas and smaller fleas: virotherapy for parasite infections.
AB  - Bacteriophages are viruses of bacteria that are used for controlling bacterial
      food-borne pathogens and have been proposed for more extensive usage in infection
      control. Protists are now recognised to harbour viruses and virus-like particles.
      We propose that investigation of their prevalence in parasites be intensified. We
      also propose that such viruses might be considered for virotherapy to control
      certain parasite infections of man and animals.

PMID- 23540831
TI  - Mechanisms of endospore inactivation under high pressure.
AB  - It is well known that spore germination and inactivation can be achieved within a
      broad temperature and pressure range. The existing literature, however, reports
      contradictory results concerning the effectiveness of different pressure
      temperature combinations and the underlying inactivation mechanism(s). Much of
      the published kinetic data are prone to error as a result of unstable process
      conditions or an incomplete investigation of the entire inactivation pathway.
      Here, we review this field of research, and also discuss an inactivation
      mechanism of at least two steps and propose an inactivation model based on
      current data. Further, spore resistance properties and matrix interactions are
      linked to spore inactivation effectiveness.

PMID- 23540832
TI  - Infectious and inflammatory complications of surgical management of cancer
      patients imaged with 18F-FDG PET/CT: a pictorial essay.
AB  - The aim of this pictorial essay was to highlight the usefulness of
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) in evaluating incidental infection or inflammation in cancer patients,
      related to surgical management. A retrospective review of 10,985 consecutive
      oncologic PET/CTs was done, and nine cases with suspected FDG positive infectious
      or inflammatory processes were selected for further review. PET/CT helped
      identify infections and inflammatory processes related to surgical management of
      cancer patients, define the extent of infection or inflammation, guide the
      management and, in some cases, evaluate response to therapy.

PMID- 23540836
TI  - Extended suicide by use of a chain saw.
AB  - Injuries caused by chain saws are mostly seen due to accidents. Suicides by chain
      saws are rare, but some cases have already been described. We present the case of
      homicide on a child by a chain saw followed by the suicide of his father. For the
      homicide and the suicide chain saws of different sizes were used. Fatal injuries
      in the homicide and suicide were located on the neck. Cause of death in both
      cases was fatal haemorrhage with blood aspiration respectively decapitation.
      Normally, in suicide by use of chain saws individuals suffering from
      schizophrenia, major depression and alcohol or drug dependence are concerned. In
      the presented case, the background was a litigation of a divorced couple for
      child custody.

PMID- 23540833
TI  - The copper active site of CBM33 polysaccharide oxygenases.
AB  - The capacity of metal-dependent fungal and bacterial polysaccharide oxygenases,
      termed GH61 and CBM33, respectively, to potentiate the enzymatic degradation of
      cellulose opens new possibilities for the conversion of recalcitrant biomass to
      biofuels. GH61s have already been shown to be unique metalloenzymes containing an
      active site with a mononuclear copper ion coordinated by two histidines, one of
      which is an unusual tau-N-methylated N-terminal histidine. We now report the
      structural and spectroscopic characterization of the corresponding copper CBM33
      enzymes. CBM33 binds copper with high affinity at a mononuclear site,
      significantly stabilizing the enzyme. X-band EPR spectroscopy of Cu(II)-CBM33
      shows a mononuclear type 2 copper site with the copper ion in a distorted axial
      coordination sphere, into which azide will coordinate as evidenced by the
      concomitant formation of a new absorption band in the UV/vis spectrum at 390 nm.
      The enzyme's three-dimensional structure contains copper, which has been
      photoreduced to Cu(I) by the incident X-rays, confirmed by X-ray
      absorption/fluorescence studies of both aqueous solution and intact crystals of
      Cu-CBM33. The single copper(I) ion is ligated in a T-shaped configuration by
      three nitrogen atoms from two histidine side chains and the amino terminus,
      similar to the endogenous copper coordination geometry found in fungal GH61.

PMID- 23540837
TI  - Unexpected death: anaphylactic intraoperative death due to Thymoglobulin
      carbohydrate excipient.
AB  - Anaphylactic shock is a life-threatening allergic response characterized by
      severe hypotension, inducing tissue hypoperfusion with possible multi-organ
      failure and death. We describe the first case of fatal intra-operative
      anaphylactic shock due to prolonged infusion of Thymoglobulin during Orthotopic
      Liver Transplantation (OLT), resulting from recruitment of both mastocytes and
      basophils, activated and degranulated. Post-mortem serological analysis on a
      preserved, pre-OLT sample of the patient's blood revealed specific IgE against
      carbohydrate cross-reactive determinants (CCDs), such as MUXF3 and nAna c2,
      proving that anaphylactic reaction was triggered by the Thymoglobulin
      carbohydrate excipient (sugar alcohol mannitol), rather than anti-thymocyte
      globulin itself. Our findings are consistent with scientific data reported in the
      literature, where only one case of non-fatal anaphylaxis to Thymoglobulin has
      been described, despite the existence of proven cases of anaphylactic reaction to
      mannitol. This case highlights the need to pay particular attention in future not
      only to active substances but also to drug excipients, above all during intra
      operative drug delivery. In view of the important role played by basophils in
      this kind of anaphylaxis, the basophil activation test (BAT) could prove useful
      in preventing anaphylactic death from CCDs.

PMID- 23540838
TI  - Antiallodynic and analgesic effects of maslinic acid, a pentacyclic triterpenoid
      from Olea europaea.
AB  - The effects of maslinic acid (1), a pentacyclic triterpenoid obtained from Olea
      europaea, were studied in several tests for nociception in mice. Systemic
      administration of 1 reduced acetic acid-induced writhing, the inflammatory phase
      of formalin-induced pain, and capsaicin-induced mechanical allodynia. However, it
      did not induce motor incoordination in the rotarod test. The topical
      administration of 1 also reduced the inflammatory phase of the formalin test,
      indicating that at least some of its effects are mediated peripherally. The
      present results demonstrate for the first time that maslinic acid induces
      antinociceptive and antiallodynic effects. 

PMID- 23540840
TI  - Trying times for generic medicines in the USA.

PMID- 23540841
TI  - Europe: a missed opportunity, with dangers and hopes.

PMID- 23540839
TI  - Small molecule regulation of protein conformation by binding in the Flap of HIV
      protease.
AB  - The fragment indole-6-carboxylic acid (1F1), previously identified as a flap site
      binder in a fragment-based screen against HIV protease (PR), has been
      cocrystallized with pepstatin-inhibited PR and with apo-PR. Another fragment, 3
      indolepropionic acid (1F1-N), predicted by AutoDock calculations and confirmed in
      a novel inhibition of nucleation crystallization assay, exploits the same
      interactions in the flap site in two crystal structures. Both 1F1 and 1F1-N bind
      to the closed form of apo-PR and to pepstatin:PR. In solution, 1F1 and 1F1-N
      raise the Tm of apo-PR by 3.5-5  degrees C as assayed by differential scanning
      fluorimetry (DSF) and show equivalent low-micromolar binding constants to both
      apo-PR and pepstatin:PR, assayed by backscattering interferometry (BSI). The
      observed signal intensities in BSI are greater for each fragment upon binding to
      apo-PR than to pepstatin-bound PR, consistent with greater conformational change
      in the former binding event. Together, these data indicate that fragment binding
      in the flap site favors a closed conformation of HIV PR. 

PMID- 23540843
TI  - Martin McKee: champion of public health in Europe.

PMID- 23540844
TI  - Postoperative radiotherapy for high-risk prostate cancer.

PMID- 23540845
TI  - Postoperative radiotherapy for high-risk prostate cancer - Authors' reply.

PMID- 23540846
TI  - Efficacy of tetravalent dengue vaccine in Thai schoolchildren.

PMID- 23540847
TI  - Efficacy of tetravalent dengue vaccine in Thai schoolchildren - Authors' reply.

PMID- 23540848
TI  - Efficacy of tetravalent dengue vaccine in Thai schoolchildren.

PMID- 23540849
TI  - Evaluation of the Affordable Medicines Facility--malaria.

PMID- 23540850
TI  - Evaluation of the Affordable Medicines Facility--malaria - Authors' reply.

PMID- 23540851
TI  - Falling out with pharma.

PMID- 23540852
TI  - Guidance on research integrity: no union in Europe.

PMID- 23540853
TI  - Triggered by The Lancet: a decade later.

PMID- 23540854
TI  - Peripheral neuropathy--lead astray?

PMID- 23540855
TI  - Imatinib and prostate cancer: lessons learned from targeting the platelet-derived
      growth factor receptor.
AB  - INTRODUCTION: The platelet derived growth factor (PDGF) signaling pathway has
      been implicated in both epithelial and stromal mechanisms of prostate cancer
      progression and postulated as a target for therapy in bone metastases. Imatinib
      mesylate is a potent inhibitor of the platelet-derived growth factor receptor
      (PDGFR) and its activity has been tested in preclinical models and in Phase I and
      II clinical trials. AREAS COVERED: This review summarizes the preclinical data on
      PDGF/PDGFR in prostate cancer, and reviews the clinical and correlative data
      using imatinib as a PDGFR inhibitor. EXPERT OPINION: To date, the use of imatinib
      to treat men with prostate cancer has been ineffective, and PDGFR inhibition may
      in fact accelerate advanced forms of the disease and antagonize taxane efficacy.
      Given the major discordance between preclinical models and clinical
      experimentation, an accurate understanding of the PDGF-regulated interactions
      between metastatic prostate cancer and the bone micro-environment is evidently
      warranted. Correlations of pharmacodynamic monitoring of imatinib-induced PDGFR
      inhibition with progression-free and overall survival outcomes have led to the
      hypothesis that PDGF may function as a homeostatic factor in bone metastases.
      Recent laboratory studies defining PDGFR-regulated pericytes as gatekeepers of
      metastases may relate to these clinical observations.

PMID- 23540856
TI  - A computational study of detoxification of lewisite warfare agents by British
      anti-lewisite: catalytic effects of water and ammonia on reaction mechanism and
      kinetics.
AB  - trans-2-Chlorovinyldichloroarsine (lewisite, L agent, Lew-I) acts as a blistering
      agents. British anti-lewisite (BAL, 2,3-dimercaptopropanol) has long been used as
      an L-agent antidote. The main reaction channels for the detoxification proceed
      via breaking of As-Cl bonds and formation of As-S bonds, producing stable,
      nontoxic ring product [(2-methyl-1,3,2-dithiarsolan-4-yl)methanol]. M06-2X/GENECP
      calculations have been carried out to establish the enhanced rate of
      detoxification mechanism in the presence of NH3 and H2O catalysts in both gas and
      solvent phases, which has been modeled by use of the polarized continuum model
      (PCM). In addition, natural bond orbital (NBO) and atoms in molecules (AIM)
      analysis have been performed to characterize the intermolecular hydrogen bonding
      in the transition states. Transition-state theory (TST) calculation establishes
      that the rates of NH3-catalyzed (2.88 * 10(-11) s(-1)) and H2O-catalyzed (2.42 *
      10(-11) s(-1)) reactions are reasonably faster than the uncatalyzed
      detoxification (5.44 * 10(-13) s(-1)). The results obtained by these techniques
      give new insight into the mechanism of the detoxification process, identification
      and thermodynamic characterization of the relevant stationary species, the
      proposal of alternative paths on modeled potential energy surfaces for
      uncatalyzed reaction, and the rationalization of the mechanistic role played by
      catalysts and solvents.

PMID- 23540857
TI  - Diagnostic radiation exposure during surveillance in patients with pT1a renal
      cell carcinoma.
AB  - OBJECTIVE: To determine the pattern of postoperative radiographic surveillance in
      patients with pT1a renal cell carcinoma (RCC) at a tertiary care hospital.
      METHODS: An institutionally approved urologic oncology database was used to
      retrospectively identify patients who underwent partial or radical nephrectomy
      for pT1a RCC from 1990 to 2010 at a tertiary care center. Baseline
      characteristics were reviewed, and postoperative imaging for the indication of
      RCC surveillance was recorded. Radiation exposure was calculated using the
      effective dose according to imaging modality. Relative risks of the development
      of solid malignancies and leukemia were calculated from the dose of radiation
      exposure. RCC recurrence, defined as radiologic evidence of local recurrence or
      distant metastases, was noted. RESULTS: A total of 1708 patients had undergone
      partial or radical nephrectomy for a renal mass. Of these, 315 patients had pT1a
      RCC with postsurgical follow-up, and 252 (80%) of these patients were exposed to
      ionizing radiation during postoperative surveillance. Mean radiation doses in
      years 1, 2 to 5, and >=6 after surgery were 11.4, 47.0, and 13.8 mSv,
      respectively. Relative risks of radiation-induced solid cancers and leukemia were
      1.05 and 1.12, respectively. There were 8 (2.5%) total recurrences. CONCLUSION:
      During the past 20 years, 80% of patients undergoing surgery for pT1a RCC were
      monitored with radiation-based imaging during postoperative surveillance. Given
      the low rate of cancer recurrence in this population, expanded efforts in
      counseling physicians regarding the risk of ionizing radiation in imaging should
      be encouraged.

PMID- 23540858
TI  - S.T.O.N.E. nephrolithometry: novel surgical classification system for kidney
      calculi.
AB  - OBJECTIVE: To, first, propose a novel scoring system to standardize reporting for
      percutaneous nephrolithotomy because the instruments currently available to
      predict the percutaneous nephrolithotomy outcomes are cumbersome, not validated,
      and of limited clinical utility; and, second, assess and predict the stone-free
      rates and perioperative parameters applying S.T.O.N.E. nephrolithometry.
      MATERIALS AND METHODS: Five reproducible variables available from preoperative
      noncontrast-enhanced computed tomography were measured: stone size (S), tract
      length (T), obstruction (O), number of involved calices (N), and essence or stone
      density (E). RESULTS: A total of 117 patients were included. The mean score was
      7.7 (range 4-11). The stone-free rate after the first procedure was 80%. There
      were 18 complications (21%). The most frequent complications were postoperative
      sepsis and bleeding. The S.T.O.N.E. score correlated with the postoperative stone
      free status (P = .001). The patients rendered stone free had statistically
      significant lower scores than the patients with residual stones (6.8 vs 9.7, P =
      .002). Additionally, the score correlated with the estimated blood loss (P =
      .005), operative time (P = .001), and length of hospital stay (P = .001).
      CONCLUSION: The novel scoring system we have presented was found to predict
      treatment success and the risk of perioperative complications after percutaneous
      nephrolithotomy. Reproducible, standardized parameters obtained from computed
      tomography imaging can be used for preoperative patient counseling, surgical
      planning, and evaluation of surgical outcomes across institutions and within
      medical studies.

PMID- 23540859
TI  - Editorial comment.

PMID- 23540860
TI  - Histopathologic and clinical features of vesical diverticula.
AB  - OBJECTIVE: To study the histopathology changes and clinical features of vesical
      diverticula, focusing on the neoplastic entities. MATERIALS AND METHODS: We
      retrieved data for 108 patients with vesical diverticula from the archives of our
      institute during the past 15 years (1998 to 2012) and reviewed their clinical and
      pathologic characteristics. RESULTS: Diverticula most often involved the lateral
      wall, followed by the posterolateral and posterior walls of the urinary bladder.
      Nonneoplastic processes were found in 70 of 108 patients (65%), including
      inflammation, metaplasia, and urothelial hyperplasia, with or without
      atypia/dysplasia. Primary carcinomas arising within the diverticula were found in
      36 patients (33.3%), of which 33 were urothelial carcinoma, including 5 with
      divergent differentiation, 2 with squamous carcinoma, and 1 with adenocarcinoma.
      Patient follow-up for neoplastic diverticula (mean, 59 months; range, 1-108
      months) showed that no patients died of disease progression. Concurrent or
      subsequent urothelial carcinoma was present in the nondiverticular bladder in 19
      of 36 patients (53%). Four patients with subsequent extradiverticular urothelial
      carcinoma showed progression, with pathology upstaging. CONCLUSION: Inflammation,
      metaplasia, and dysplasia are commonly seen in vesical diverticula. In our
      series, which includes patients who underwent endoscopic or surgical intervention
      and microscopic examination, those with vesical diverticula appeared to have a
      significantly higher risk for development of urothelial carcinoma, which can
      occur synchronously or precede carcinoma of the nondiverticular bladder. Compared
      with their non-diverticulum-associated counterparts, a significantly higher
      percentage of diverticulum-associated bladder carcinomas are high-grade and
      invasive. Conservative approaches are suggested for tumors confined within
      diverticula, after extensive investigation of the nondiverticular bladder.

PMID- 23540861
TI  - Differential spermatozoal protein expression profiles in men with varicocele
      compared to control subjects: upregulation of heat shock proteins 70 and 90 in
      varicocele.
AB  - OBJECTIVE: To identify candidate proteins with potential roles in varicocele.
      METHODS: This case-control study recruited 20 patients with varicocele (grade II)
      and 20 age-matched healthy control subjects. Two-dimensional gel electrophoreses
      (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF MS) were used to screen for and identify differentially
      expressed proteins in sperm samples from the 40 study subjects. RESULTS: A total
      of 15 proteins were repeatedly detected with significant differences in percent
      spot volume (P <.05) and were identified as proteins of interest. Of these, 4
      showed significantly lower expression in the varicocele group compared to the
      control group, and 11 showed significantly higher expression in the varicocele
      group, including heat shock proteins (HSPs) 70 and 90. Significant upregulation
      of HSP 70 and HSP 90 in subjects with varicocele was further validated by Western
      blot and immunocytochemistry. CONCLUSION: These results suggest that increased
      expression of HSP 70 and HSP 90 may be associated with infertility in varicocele.
      Delineation of a potential subset of heat-related proteins specifically regulated
      in the context of varicocele may allow for the detailed elucidation of the
      mechanism underlying infertility in this condition.

PMID- 23540862
TI  - Unusual presentation of ectopic insertion of duplicated collecting system in an
      adult male.
AB  - Ectopic ureters are rare congenital mesonephric duct malformations with a higher
      prevalence in women than men. In women, ectopic ureters are often associated with
      a duplicated collecting system, whereas in men, ectopic ureters usually drain a
      single system and are associated with renal dysplasia and obstruction.
      Presentation and diagnosis generally occurs in the pediatric age group. Herein,
      we present an unusual case of delayed diagnosis of ectopic insertion of the upper
      pole ureter in a completely duplicated left kidney causing massive
      hydroureteronephrosis in an adult man.

PMID- 23540863
TI  - Toxicity after external beam radiotherapy for prostate cancer: an analysis of
      late morbidity in men with diabetes mellitus.
AB  - OBJECTIVE: To investigate the influence of diabetes mellitus (DM) on late
      genitourinary (GU) and gastrointestinal (GI) toxicity in patients treated with
      external beam radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: A
      total of 626 men were treated with curative-intent RT for prostate cancer from
      1988 to 2008. Using the National Comprehensive Cancer Network risk category, the
      patients were considered to have low-risk (30%), intermediate-risk (42%), or high
      risk (28%) prostate cancer. The median radiation dose was 74 Gy; 45% received
      androgen deprivation therapy for a median of 4 months. Late GU and GI Radiation
      Therapy Oncology Group toxicity was recorded prospectively at each visit after
      external beam RT. The median follow-up period was 55 months. RESULTS: Of the 626
      men, 102 (16%) had DM that was controlled by diet (8%), oral medications (52%),
      or insulin (39%). The patients with DM were more likely to receive intensity
      modulated RT and androgen deprivation therapy and to have a shorter follow-up
      duration (P <=.05 for all). Univariate analyses demonstrated that greater
      radiation dose, baseline urinary dysfunction, intensity-modulated RT, and DM were
      associated with grade 2 or greater GU toxicity, and transurethral resection of
      the prostate and DM were associated with grade 3 or greater GU toxicity. In
      addition, androgen deprivation therapy use, age >=70 years, and anticoagulation
      were associated with grade 2 or greater GI toxicity, and age >=70 years and
      anticoagulation were associated with grade 3 or greater GI toxicity. The
      multivariate analyses for late toxicity demonstrated a greater risk of grade 2 or
      greater (relative risk 1.36, P = .10) and grade 3 or greater GU toxicity
      (relative risk 2.74, P = .04) with DM. CONCLUSION: A greater incidence of late GU
      toxicity was seen in patients with DM treated for prostate cancer. This
      relationship might be useful when considering the treatment of patients with DM,
      especially those receiving dose-escalated RT or with a history of transurethral
      resection of the prostate.

PMID- 23540864
TI  - Reply: To PMID 23540858.

PMID- 23540865
TI  - Targeted MRI-guided prostate biopsies for the detection of prostate cancer:
      initial clinical experience with real-time 3-dimensional transrectal ultrasound
      guidance and magnetic resonance/transrectal ultrasound image fusion.
AB  - OBJECTIVE: To prove the feasibility and evaluate the initial clinical results of
      targeted prostate biopsies using the Urostation novel platform using magnetic
      resonance imaging (MRI)/transrectal ultrasound (TRUS) registration to help steer
      the biopsy needle to suspicious areas. METHODS: We prospectively included 30
      patients for suspicion of prostate cancer from November 2011 to August 2012. All
      patients were previously evaluated by a multiparametric MRI, interpreted by a
      single radiologist who attributed a Prostate Imaging-Reporting and Data System
      (PI-RADS) score to each lesion. A conventional 12-core randomized biopsy protocol
      was performed and 2 additional targeted biopsies were performed on suspicious
      area(s). The results of randomized and targeted biopsies were compared. RESULTS:
      Among the 30 patients, suspicious area(s) were found on MRI in 20 cases (67%).
      Median procedure time was 23 minutes. Targeting success rate (biopsy visualized
      inside the target) was 83%, with at least 1 biopsy reaching the target in all
      cases. Prostate cancer was detected in 14 cases (47%), including 11 cases with an
      abnormal MRI. Targeted biopsies detected cancer in all 11 cases and all but 1
      were clinically significant. Randomized biopsies detected 10 of these 11 cases,
      and 3 more cases that MRI considered normal. Sensitivity to detect a significant
      cancer was 91% in both modalities. CONCLUSION: This initial clinical study showed
      encouraging results for targeted MRI-guided prostate biopsies using MRI-TRUS
      fusion. Although further studies are needed to determine the role of prostate MRI
      before biopsy and the relevance of targeted biopsies, the Urostation is an MRI
      TRUS fusion device that has good accuracy for targeting suspicious areas on MRI.

PMID- 23540866
TI  - Dose-escalation study of three-dimensional conformal thoracic radiotherapy with
      concurrent S-1 and cisplatin for inoperable stage III non-small-cell lung cancer.
AB  - PURPOSE: To determine the recommended dose (RD) in concurrent conformal
      radiotherapy with S-1 and cisplatin chemotherapy for inoperable stage III non
      small-cell lung cancer. PATIENTS AND METHODS: Eligible patients with inoperable
      stage III non-small-cell lung cancer, age >= 20 years, performance status 0-1
      received 4 cycles of intravenous cisplatin (60 mg/m(2), day 1) and oral S-1 (80,
      100, or 120 mg based on body surface area, days 1-14) repeated every 4 weeks.
      Radiation doses were 66, 70, and 74 Gy for arms 1, 2, and 3, respectively.
      RESULTS: A total of 24 patients were enrolled in our study, including 6 in arm 1,
      6 in arm 2, and 12 in arm 3. The patients consisted of 14 men and 10 women, with
      a median age of 63 years (range, 44-73 years). The median follow-up was 27.3
      months (range, 8.5-42.6 months) for all patients and 33.9 months (range, 15.2
      42.6 months) for those still alive. Grade 3 febrile neutropenia, lung toxicities,
      and heart toxicities occurred in 2, 2, and 2 patients, respectively. Dose
      limiting toxicity occurred in 2, none, and 1 patient in arms 1, 2, and 3,
      respectively. The median survival was not reached, and the 2-year survival rate
      was 70% (95% CI, 51%-89%). Two-year local relapse-free survival and distant
      metastasis-free survival were 74% (95% CI, 56%-92%) and 45% (95% CI, 25%-65%),
      respectively. CONCLUSIONS: High-dose radiotherapy with S-1 and cisplatin is
      feasible, and 74 Gy was determined as the recommended dose.

PMID- 23540867
TI  - Concurrent molecular alterations in tumors with germ line epidermal growth factor
      receptor T790M mutations.

PMID- 23540868
TI  - Reply to letter to the editor re: "ultrasonography for diagnosing carpal tunnel
      syndrome: a meta-analysis of diagnostic test accuracy".

PMID- 23540869
TI  - Re: "ultrasonography for diagnosing carpal tunnel syndrome: a meta-analysis of
      diagnostic test accuracy".

PMID- 23540870
TI  - Synthesis and characterization of low-generation polyamidoamine (PAMAM) dendrimer
      sodium montmorillonite (Na-MMT) clay nanocomposites.
AB  - Polymer-inorganic nanocomposites are a recently developed class of materials that
      have altered physical or chemical properties with respect to the pure polymer,
      inorganic host, or their micro- and macrocomposites. Lower generation (G0.0-2.0)
      polyamidoamine (PAMAM) dendrimer/sodium montmorillonite (Na-MMT) nanocomposites
      were synthesized in a solution-phase exfoliation adsorption reaction. These are
      the first reports of the G0.0/ and G1.0/Na-MMT nanocomposites and of a
      structurally-ordered G2.0/Na-MMT. The materials were characterized using powder X
      ray diffraction (PXRD), thermogravimetric analysis (TGA), and Fourier transform
      infrared spectroscopy (FTIR). PAMAM characteristics at acidic and basic aqueous
      media were studied using capillary zone electrophoresis (CZE). Pseudospherical
      PAMAM dendrimers in aqueous medium attain a highly flattened conformation within
      the confined space between MMT sheets upon nanocomposite formation. The
      nanocomposite structure depends on the PAMAM generation and the starting
      dendrimer/organic composition. G0.0 always forms monolayer structures (d = 0.42
      nm), while G2.0 forms monolayer structure, mixed phase, and bilayer structures (d
      = 0.84 nm) at lower, intermediate, and higher organic content, respectively,
      showing an interesting monolayer to bilayer transition. G1.0 showed an
      intermediate behavior, with monolayer to mixed-phase transition at the reactant
      ratios studied. This monolayer arrangement of PAMAM/clay nanocomposites is
      reported for the first time. Maximum organic contents of G0.0 monolayer and G2.0
      bilayer nanocomposites were ~7% and ~14%, respectively. Gallery expansions were
      similar to those observed with linear polymer intercalates, but the packing
      fractions (0.31-0.32) were 2-3 times lower. At acidic pH, the nanocomposites
      forming only monolayer structures are obtained, indicating a stronger
      electrostatic attraction between MMT and protonated PAMAM, and these
      nanocomposites formed more slowly and were more ordered. Na(+) ions play a
      significant role in nanocomposite formation. At high pH, PAMAMs show high
      mobility, zeta potential, and surface charge densities due to Na(+) complexation
      in solution. FTIR data indicates that both Na-MMT and PAMAM structural units are
      preserved in the nanocomposites obtained.

PMID- 23540871
TI  - Obesity and asthma control: do gender, age, and ethnicity really matter?

PMID- 23540872
TI  - Chronic obstructive pulmonary disease is just one component of the complex
      multimorbidities in patients with COPD.

PMID- 23540873
TI  - Predicting the development of acute respiratory distress syndrome: searching for
      the "Troponin of ARDS".

PMID- 23540874
TI  - Statins and sepsis: potential benefit but more unanswered questions.

PMID- 23540875
TI  - Acute respiratory distress syndrome and stem cells: a small beginning or a
      strategy doomed to never gestate?

PMID- 23540876
TI  - The Berlin definition of ARDS versus pathological evidence of diffuse alveolar
      damage.

PMID- 23540877
TI  - Idiopathic pulmonary fibrosis pathogenesis and novel approaches to
      immunomodulation: we must not be tyrannized by the PANTHER data.

PMID- 23540878
TI  - Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung
      health.
AB  - RATIONALE: Cystic fibrosis (CF) is an autosomal recessive disease characterized
      by abnormal airways secretions, chronic endobronchial infection, and progressive
      airway obstruction. The use of medications to slow the progression of lung
      disease has led to significant improvement in survival. An evidence review of
      chronic medications for CF lung disease was performed in 2007 to provide guidance
      to clinicians in evaluating and selecting appropriate treatment for individuals
      with this disease. We have undertaken a new review of the literature to update
      the recommendations, including consideration of new medications and additional
      evidence on previously reviewed therapies. A multidisciplinary committee of
      experts in CF pulmonary care was established to review the evidence for use of
      chronic medications for CF lung disease and make treatment recommendations.
      Published evidence for chronic lung therapies was systematically reviewed and
      resulting treatment recommendations were graded based on the United States
      Preventive Services Task Force scheme. These guidelines provide up-to-date
      evidence of safety and efficacy of chronic treatments of CF lung disease,
      including the use of novel therapies that have not previously been included in CF
      pulmonary guidelines.

PMID- 23540879
TI  - Real-time vision of a sarcoid granuloma at bronchoscopy.

PMID- 23540880
TI  - The clinical utility of bronchoalveolar lavage cellular analysis in interstitial
      lung disease.

PMID- 23540881
TI  - Reply: The clinical utility of bronchoalveolar lavage cellular analysis in
      interstitial lung disease.

PMID- 23540882
TI  - Comments on the neonatal bacillus Calmette-Guerin vaccination: adding notes in
      proof of nonspecific effect.

PMID- 23540883
TI  - Reply: Bacille Calmette-Guerin vaccine: innate immunity and nonspecific effects.

PMID- 23540884
TI  - Sounds, ultrasounds, and artifacts: which clinical role for lung imaging?

PMID- 23540885
TI  - Mask ventilation and dispersion of exhaled air.

PMID- 23540886
TI  - EUTOS CML prognostic scoring system predicts ELN-based 'event-free survival'
      better than Euro/Hasford and Sokal systems in CML patients receiving front-line
      imatinib mesylate.
AB  - OBJECTIVES: The validity of the three currently used chronic myeloid leukemia
      (CML) scoring systems (Sokal CML prognostic scoring system, Euro/Hasford CML
      scoring system, and the EUTOS CML prognostic scoring system) were compared in the
      CML patients receiving frontline imatinib mesylate. PATIENTS AND METHODS: One
      hundred and fourty-three chronic phase CML patients (71 males, 72 females) taking
      imatinib as frontline treatment were included in the study. The median age was 44
      (16-82) years. Median total and on-imatinib follow-up durations were 29 (3.8-130)
      months and 25 (3-125) months, respectively. RESULTS: The complete hematological
      response (CHR) rate at 3 months was 95%. The best cumulative complete cytogenetic
      response (CCyR) rate at 24 months was 79.6%. Euro/Hasford scoring system was well
      correlated with both Sokal and EUTOS scores (r = 0.6, P < 0.001 and r = 0.455, P
      < 0.001). However, there was only a weak correlation between Sokal and EUTOS
      scores (r = 0.2, P = 0.03). The 5-year median estimated event-free survival for
      low and high EUTOS risk patients were 62.6 (25.7-99.5) and 15.3 (7.4-23.2)
      months, respectively (P < 0.001). This performance was better than Sokal (P =
      0.3) and Euro/Hasford (P = 0.04) scoring systems. Overall survival and CCyR rates
      were also better predicted by the EUTOS score. DISCUSSION: EUTOS CML prognostic
      scoring system, which is the only prognostic system developed during the imatinib
      era, predicts European LeukemiaNet (ELN)-based event-free survival better than
      Euro/Hasford and Sokal systems in CML patients receiving frontline imatinib
      mesylate. This observation might have important clinical implications.

PMID- 23540887
TI  - Body size dissatisfaction and avoidance behavior: how gender, age, ethnicity, and
      relative clothing size predict what some won't try.
AB  - Sixty-eight percent of U.S. adults are overweight/obese, and this epidemic has
      physical, psychosocial, and behavioral consequences. An internet sample of adults
      (N=2997) perceiving themselves as larger than ideal in clothing size reported
      their body mass index (BMI), relative clothing size (RS; discrepancy between
      current and ideal size), and avoidance behaviors. Exploratory factor analysis of
      10 avoidance items produced social avoidance and body display avoidance factors.
      A relative importance analysis revealed RS as a better predictor than BMI for
      avoidance. A hierarchical multivariate analysis of covariance found RS to predict
      both avoidance constructs. The relationship between RS and both avoidance
      constructs was stronger for women than men, and for younger as compared to older
      participants. Caucasians reported more body display avoidance than African
      Americans. This suggests that personal dissatisfaction with body size may deter
      involvement in varied life events and that women are especially avoidant of
      activities that entail displaying their bodies.

PMID- 23540888
TI  - Otologic manifestations from blast injuries among military personnel in Thailand.
AB  - BACKGROUND: From November 2008 to October 2010, 565 military personnel sustained
      blast injury in Southernmost Thailand and 99 personnel, affected by multiple
      injuries, were transferred to Phramongkutklao Hospital. No data on the effect of
      blast injury to the ears among Thai military personnel have been reported. This
      study aims 1) to determine the prevalence of Sensorineural Hearing Loss (SNHL)
      and otologic manifestations from primary blast injury among military personnel,
      in Pattani, Yala and Narathiwat Provinces, and 2) to evaluate the impact of
      explosive devices and distance from explosion on SNHL under various conditions.
      MATERIALS AND METHODS: A cross-sectional study was conducted among 76 military
      personnel injured from blast injury in Southernmost Thailand. They were divided
      into three groups representing the bomb blast settings; open-space referred to an
      area without barrier, semi-open space referred to a room open on at least one
      side and closed space referred to a room enclosed with four walls and ceiling.
      RESULTS: The otologic manifestations from 76 patients were tinnitus, tympanic
      membrane perforation, bleeding and open wound. The prevalence of SNHL among
      patients in the open-, semi-open and closed space groups was 62.77%, 67.86% and
      73.33%, respectively. The most common type of explosive was Improvised Explosive
      Devices (IEDs) 72 (94.74%). The average IED weighed 11.42kg and mean distance
      from explosion was 5.66m. CONCLUSION: Correlation among all three incident areas
      and two factors: impact of explosive devices and distance from explosion are risk
      factors of SNHL without significance.

PMID- 23540889
TI  - Oral cavity squamous cell carcinoma in never smokers: analysis of
      clinicopathologic characteristics and survival.
AB  - PURPOSE: To examine the relationship between tobacco smoking history and the
      clinicopathologic and survival characteristics of patients with oral cavity
      squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: This is a retrospective
      review of 531 patients treated for OCSCC from January 1998 to December 2009 at a
      tertiary care medical center. RESULTS: Thirty-two percent of OCSCC patients were
      never smokers. There were significant differences in tumor location between ever
      smokers and never smokers (p<0.001), with never smokers more likely to have oral
      tongue tumors. Smokers were significantly (p<0.001) more likely than never
      smokers to present with locally advanced (T3 or T4) disease (57.8% vs. 35.4%).
      Never smokers demonstrated improved overall survival (78.8 months in never
      smokers vs. 44.7 months in ever smokers, p=.03). However, there were no survival
      differences when the two groups were compared separately for locally early
      (T1/T2) or advanced (T3/T4) disease. For T1/T2 tumors, mean survival was 88.2
      months for never smokers and 78.5 months for smokers (p=.10). For T3/T4 tumors,
      median survival was 29.1 months for never smokers and 23.8 months for smokers
      (p=.09). CONCLUSIONS: Primary tumor location and T-status in OCSCC differed
      between never smokers and smokers. Compared to smokers, never smokers had fewer
      locally advanced tumors and better overall survival.

PMID- 23540890
TI  - Qualitative evidence from a systematic review of prognostic predictors for
      surgical outcomes following cervical ossification of the posterior longitudinal
      ligament.
AB  - Ossification of the posterior longitudinal ligament (OPLL) is a pathological
      ectopic ossification of this ligament that usually occurs in the cervical spine.
      For patients with cervical OPLL and neurological symptoms, surgical intervention
      is necessary but not always effective. Various prognostic factors influence the
      surgical outcome. The results of studies identifying these prognostic predictors
      are often inconclusive or contradictory. These predictors have not been well
      identified or summarized. The present study was designed to identify the
      prognostic predictors for the surgical outcome of cervical OPLL based on the
      available evidence in the literature. Non-interventional studies were searched in
      Medline, Embase, Science Direct, OVID and the Cochrane library. Forty-two
      observational studies involving 2791 patients were included. The quality of the
      included studies was assessed with a modified quality assessment tool, which was
      originally designed for use with observational studies. The effects of the
      studies were combined with the study quality score using a model of best-evidence
      synthesis. There was strong evidence for five predictors: (i) age, (ii) duration
      of symptoms, (iii) pre-operative neurological score, (iv) transverse area of the
      spinal cord, and (v) intramedullary high signal intensity on the T2-weighted MRI.
      We also identified eight predictors with moderate supporting evidence, seven with
      limited evidence, four with conflicting evidence and four predictors without
      supporting evidence. While there is no conclusive evidence regarding the surgical
      outcomes following cervical OPLL, these data provide evidence to guide the
      clinician in choosing an optimal therapeutic strategy for patients with cervical
      OPLL. Further research is necessary to fully evaluate the effects of the
      predictors described in this study.

PMID- 23540891
TI  - Intracisternal administration of SB203580, a p38 mitogen-activated protein kinase
      inhibitor, attenuates cerebral vasospasm via inhibition of tumor-necrosis factor
      alpha.
AB  - Tumor-necrosis factor-alpha (TNF-alpha) is critical to the development of
      cerebral vasospasm after subarachnoid hemorrhage (SAH). Hence, therapeutic
      strategies targeting TNF-alpha can attenuate cerebral vasospasm. This study
      investigated the effects of SB203580, a p38 mitogen-activated protein kinase
      (MAPK) inhibitor, on TNF-alpha concentration in the cerebral arteries and the
      cerebrospinal fluid (CSF) after SAH and on subsequent cerebral vasospasm. Twenty
      three rabbits were divided into four groups: (i) control (without SAH), (ii) SAH
      (SAH only), (iii) dimethylsulfoxide (DMSO, vehicle), and (iv) SB203580. The
      severity of vasospasm and the immunoreactivities of TNF-alpha and phosphorylated
      p38 MAPK in the brain vessels were determined in all animals, and the
      concentrations of TNF-alpha in the CSF were also assessed. Severe vasospasm was
      observed in the rabbits from the SAH and DMSO groups. SB203580 reversed vasospasm
      after SAH. Lower immunoreactivities of TNF-alpha and phosphorylated p38 MAPK were
      found in the basilar artery in the SB203580 group than in the DMSO group. The
      concentration of TNF-alpha in the CSF increased after SAH, but treatment with
      SB203080 after SAH suppressed this increase. Our data show that SB203580 reversed
      cerebral vasospasm by inhibiting the phosphorylation of p38 MAPK in the basilar
      artery and by suppressing the increase in TNF-alpha in the basilar artery and CSF
      after SAH. SB203580 could therefore potentially be used for the treatment of
      cerebral vasospasm after SAH.

PMID- 23540892
TI  - Vitamin D and multiple sclerosis.
AB  - The role of vitamin D supplementation in preventing multiple sclerosis (MS)
      and/or treating MS progression is an area of significant research interest. We
      detail the current status of the ongoing research in this field, and note the
      lack of class 1 evidence from well-conducted, large, double-blind, placebo
      controlled studies of vitamin D supplementation in the prevention and/or
      treatment of MS. We have been able to provide some guidelines for practitioners
      based on the substantial burden of supportive evidence for the use of vitamin D
      in MS as summarised here. These guidelines may provide some support to those
      clinicians who treat people with MS and their families.

PMID- 23540893
TI  - Use of intravenous tranexamic acid in total knee arthroplasty: a meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: The effect of tranexamic acid (TA) on patients receiving total knee
      arthroplasty (TKA) has been reported in many small clinical trials. But single
      trials are not sufficient enough to clarify the effectiveness and safety of TA.
      So, we carried out a meta-analysis of randomized controlled trials to investigate
      the efficacy and safety of the intravenous use of TA in TKA. METHODS: Literatures
      were retrieved in Cochrane Library, OVID, PubMed, EMBASE, CNKI and Wanfang Data.
      All the related literatures were checked by two independent investigators and
      only the high quality randomized controlled trials were enrolled. Relevant data
      were analyzed using RevMan 5.1 to compare the difference of blood loss,
      transfusion and complications between TA group and control group. RESULTS: There
      were 353 related literatures and only 22 randomized controlled trials met the
      inclusion criteria. The use of TA in TKA significantly reduced total blood loss
      by a mean of 435.41 ml (95% CI 300.62-570.21, P less than 0.01), post-operative
      blood loss by a mean of 406.69 ml (95% CI 333.16-480.22, P less than 0.01). TA
      also significantly lowered the transfusion rate (risk difference 0.30, 95% CI
      0.21-0.39, P less than 0.01) and transfusion volume (mean difference 0.95 unit,
      95% CI 0.53-1.37, P less than 0.01). The risks between TA group and control group
      in developing deep vein thrombosis and pulmonary embolism were not statistically
      significant. CONCLUSION: TA is beneficial for patients undergoing TKA, which can
      significantly reduce total blood loss, postoperative blood loss, transfusion
      rate, and transfusion volume. Meanwhile TA is recommended to reduce deep vein
      thrombosis and pulmonary embolism following TKA.

PMID- 23540894
TI  - Results of titanium elastic nailing in paediatric femoral diaphyseal fractures---
      report of 30 cases.
AB  - OBJECTIVE: Fractures of the femur are the most incapacitating fractures. For
      children aged 6-14 years, there is no clear consensus as to the preferred
      treatment. The conventional treatment of traction and casting is no longer
      recommended. We report our experience in titanium elastic nailing for treatment
      of paediatric femoral diaphyseal fractures. METHODS: Thirty patients in the age
      group of 6-16 years with displaced diaphyseal femoral fractures were stabilized
      with titanium elastic nails. Patients were followed up clinically and
      radiologically for a minimum period of 1 year. The final results were evaluated
      using Flynn's criteria. Technical difficulties and complications associated with
      the procedure were also analysed. RESULTS: Overall results were excellent in 20
      cases and satisfactory in 10 cases. No patient had poor result. The average
      hospital stay was 9 days. All the fractures healed with an average time to union
      of 6.86 weeks. The most common complication encountered was soft tissue
      irritation at the nail entry site seen in 6 cases. Clinically, lengthening was
      noticed in 4 cases, while no patient had shortening. Malalignment was seen in
      only 6 cases. Perioperative difficulties encountered were failure of closed
      reduction seen in 6 cases and corkscrewing of nails in one case. CONCLUSION:
      Titanium elastic nails are a relatively easy to use, minimally invasive, physeal
      protective implant system with high rate of good and excellent outcomes in
      children aged 6-16 years. Technical pitfalls can be eliminated by adhering to the
      basic principles.

PMID- 23540895
TI  - Time analysis of fatal traffic accidents in Fars Province of Iran.
AB  - OBJECTIVE: To analyze the time factor in road traffic accidents (RTAs) in Fars
      Province of Iran. METHODS: This study was conducted in Fars Province, Iran from
      November 22, 2009 to November 21, 2011. Victims'information consisted of age,
      sex, death toll involving dri- vers or passengers of cars, motorcycles and
      pedestrians, and site of injury etc. Accidents were analyzed in relation to hour
      of the day, season of the year, lighting condition including sunrise, sunset,
      daytime and nighttime. RESULTS: A total of 3 642 deaths (78.3% were males, and
      the ratio of males to females was about 3.6:1) were studied regarding their
      autopsy records. There was a steady increase in fatal accidents occurring at
      midnight to 15:59. The risk of being involved in a fatal traffic accident was
      higher for those injured between 4:00 to 7:59 than at other times (OR equal to
      2.13, 95% CI 1.85-2.44). The greatest number of fatal RTAs took place in summer.
      Mortalities due to RTA during spring and summer were more pronounced at 20:00 to
      23:59 and midnight to 3:59, whereas mortalities in fall and winter were more
      pronounced from 12:00 to 15:59. CONCLUSION: The high mortality rate of RTA is a
      major public health problem in Fars Province. Our results indicate that the time
      is an important factor which contributes to road traffic deaths.

PMID- 23540896
TI  - Outcome of penetrating cardiac injuries in southern Iran, Shiraz.
AB  - OBJECTIVE: Cardiac injuries are one of the most challenging injuries in the field
      of trauma surgery. Their management often requires immediate surgical
      intervention, excellent surgical technique and the ability to provide excellent
      postoperative critical care to patients. The aim of this study was to evaluate
      the outcome and survival rate of patients with penetrating cardiac injury in
      southern Iran, Shiraz. METHODS: From January 2001 to June 2007, medical records
      of all patients suffering from penetrating cardiac injuries were reviewed and
      their outcomes were investigated. The inclusion criterion was the presence of a
      confirmed penetrating cardiac injury intraoperatively or by autopsy. Patients
      with blunt cardiac injuries were excluded from the study. RESULTS: The study
      consisted of 37 patients, including 1 gunshot wound (2.7%), 35 stab wounds
      (94.6%) and 1 (2.7%) shotgun wound. The overall survival rate was 76% (28 in 37)
      and that in stab wound patients was 80%. The collected data of 9 expired patients
      revealed 11% death on arrival, 67% hypotensive, and 22% normotensive considering
      physiologic presentation. Paired sample test showed significant correlation
      between mortality and electrocardiographic changes, amount of retained blood in
      pericardium, clinical stage and physiologic condition at presentation, as well as
      associated injury type (gunshot more than stab wound). CONCLUSION: Our results
      show that injury mechanism and initial cardiac rhythm are significant predictors
      of outcomes in patients with penetrating cardiac injuries. Besides, gunshot
      injury and exsanguination are the most important predictive variables of
      mortality.

PMID- 23540897
TI  - Predictors of early outcome in unstable pelvic fractures.
AB  - OBJECTIVE: To define the preoperative and intraoperative variables which may
      affect the immediate postoperative outcome in surgically managed patients with
      unstable pelvic fractures. METHODS: This study was performed prospectively from
      January 2009 to June 2011 on 36 consecutive patients admitted to the trauma ward
      of Postgraduate Institute of Medical Education and Research, Chandigarh, with
      unstable pelvic injuries. RESULTS: In the present study of 36 patients, 29 were
      managed surgically. Surgical duration was 2 hours in patients operated on within
      1 week and 3.4 hours in those operated on after 1 week. The blood loss was 550 ml
      when surgery was done after a week, but when done within a week it was 350 ml.
      The average blood loss through Pfanenstial approach was 360 ml, through posterior
      approach was 408 ml and through combined approach was 660 ml which was
      significantly high. CONCLUSION: Anterior approach to the pelvis would cause
      significantly more amount of blood loss than posterior approach and external
      fixation. Surgical approaches do not have any influence on the surgical duration
      or the infection rate. The blood loss significantly increases when the surgical
      time is more than 1 h. The infection rate is not influenced by the duration of
      surgery. Presence or absence of associated injuries to the head, chest or abdomen
      is the main determinants of patient's survival and it greatly influences the
      duration of hospital stay.

PMID- 23540898
TI  - Zero drift of intraventricular and subdural intracranial pressure monitoring
      systems.
AB  - OBJECTIVE: To assess zero drift of intraventricular and subdural intracranial
      pressure (ICP) monitoring systems. METHODS: A prospective study was conducted in
      patients who received Codman ICP monitoring in the neurosurgical department from
      January 2010 to December 2011. According to the location of sensors, the patients
      were categorized into two groups: intraventricular group and subdural group. Zero
      drift between the two groups and its association with the duration of ICP monitor
      were analyzed. RESULTS: Totally, 22 patients undergoing intraventricular ICP
      monitoring and 27 receiving subdural ICP monitoring were enrolled. There was no
      significant difference in duration of ICP monitoring, zero drift value and its
      absolute value between intraventricular and subdural groups (5.38 d+/-2.58 d vs
      4.58 d+/-2.24 d, 0.77 mm Hg+/-2.18 mm Hg vs 1.03 mm Hg+/-2.06 mm Hg, 1.68 mm Hg+/
      1.55 mm Hg vs 1.70 mm Hg+/-1.53 mm Hg, respectively; all P larger than 0.05).
      Absolute value of zero drift in both groups significantly rose with the increased
      duration of ICP monitoring (P less than 0.05) while zero drift value did not.
      Moreover, daily absolute value in the intraventricular group was significantly
      smaller than that in the subdural group (0.27 mm Hg+/-0.32 mm Hg vs 0.29 mm Hg+/
      0.18 mm Hg, P less than 0.05). CONCLUSION: This study demonstrates that absolute
      value of zero drift significantly correlates with duration of both
      intraventricular and subdural ICP monitoring. Due to the smaller daily absolute
      value, ICP values recorded from intraventricular system may be more reliable than
      those from subdural system.

PMID- 23540899
TI  - Bipolar hemiarthroplasty with a two-step osteotomy technique for unstable
      intertrochanteric fracture in senile patients.
AB  - OBJECTIVE: To introduce bipolar hemiarthroplasty with a two-step osteotomy
      technique and observe its clinical result for unstable intertrochanteric
      fractures in senile patients. METHODS: Fifteen consecutive patients with unstable
      intertrochanteric fractures aged from 81 to 92 years with a mean of 85 years were
      treated in our hospital from August 2006 to October 2011 (Evans type III in 4
      cases, Evans type IV in 11 cases), who received bipolar hemiarthroplasty with a
      two-step osteotomy technique performed by a senior orthopedic surgeon through
      posterior approach under general anesthesia. All cases were evaluated by
      Zuckerman functional recovery score (FRS) and operative risk assessment software
      1, based on the patients' physical and laboratory examinations preoperatively.
      The duration and blood loss have been recorded. There were 4 male cases (4 hips)
      and 11 female cases (11 hips). All prostheses consisted of Link SP II femoral
      stem and bipolar femoral head. All patients were followed up for more than 1
      year. RESULTS: The average preoperative FRS, predictive value of operative
      morbidity and mortality were 83.7 (81.7-85.9), 9.3% (7.3%-15.0%) and 3.5% (2.3%
      4.2%), respectively. The average operation time was 50 minutes with a mean
      intraoperative blood loss of 310 ml. There were no operative or anesthetic
      complications or deaths within 30 days after operation. Sitting up was permitted
      3 to 4 days, and partial weight bearing was allowed 5 to 7 days after operation.
      The average FRS was 79.3 at 30 days and 84.9 at 1 year postoperatively. Three
      patients died of unrelated causes (one due to myocardial infarction and the
      others due to cerebral hemorrhage during at least one-year follow-up).
      CONCLUSION: Bipolar hemiarthroplasty with a two-step osteotomy technique for
      unstable intertrochanteric fractures in the senile patients is a good choice for
      early ambulation and good hip function.

PMID- 23540900
TI  - Treatment of type III middle phalangeal neck fractures through a palmar approach:
      a case report.
AB  - Phalangeal neck fractures occur almost exclusively in children. We present the
      case of a 49 years old man with a dislocated fracture of the neck of the middle
      phalanx with the distal fragment rotated at 180? due to a traumatic circular saw
      injury to the left index, which was solved by anatomical reduction and bone
      fixation with two 1.5 mm Synthes screws and a temporary transarticular K-wire at
      the distal interphalangeal joint. Zone I flexor digitorum profundus repair was
      performed using a modification of the Kessler 4-strands core suture and a full
      thickness skin graft from the hypothenar eminence was taken to cover the skin
      gap. At 6-month follow-up the patient was pain-free and with a total active
      movement equivalent to 190? No radiological signs of avascular necrosis of the
      head of the middle phalanx or nonunion of the distal fragment was detectable with
      recovery to the previous manual work. Owing to the position of the phalangeal
      head maintained in position by the collateral ligaments an anatomic reduction
      from dorsal approach is difficult to be performed and a longitudinal traction can
      render the reduction harder too. The volar approach permits an easier reduction
      of the fracture through a derotation of the distal fragment facing palmar.

PMID- 23540901
TI  - Multiple floating metatarsals: a unique injury.
AB  - Concomitant dislocation of the tarsometatarsal and metatarsophalangeal joints of
      foot is an extremely rare injury. Such injuries presenting in a single or
      adjacent dual rays have been described in few cases previously. We describe such
      an injury in adjacent three metatarsals of a polytrauma patient. These injuries
      are likely to be missed in the initial assessment of a polytrauma patient. These
      patients are at risk of an overlooked diagnosis but the consequences of missing
      this type of injury may be quite severe. This case is presented in view of its
      uniqueness along with possible mechanism of injury, the sequence of reduction and
      follow-up. Knowledge of such injury and its proper management may be useful to
      the trauma surgeons.

PMID- 23540902
TI  - Bilateral stress fractures of femoral neck in non-athletes: a report of four
      cases.
AB  - Femoral neck stress fractures (FNSFs) are rare, constituting only 5% of all
      stress fractures in young adults. These fractures are usually seen in athletes,
      military recruits and patients with underlying metabolic diseases. The treatment
      of FNSFs is still controversial because of the inherent complications associated
      with the treatment procedure. We came across 4 cases of bilateral FNSFs in non
      athletic individuals who were manual labourers without underlying bony disorders.
      Two patients with FNSFs and coxa vara deformity on both sides were managed by
      subtrochanteric valgus osteotomy and dynamic hip screw fixation. One of the
      remaining two patients was treated by cannulated cancellous screw fixation on one
      side and subtrochanteric valgus osteotomy on the other side. The fourth patient
      received subtrochanteric valgus osteotomy on one side and bipolar
      hemiarthroplasty on the other side after failed cannulated screw fixation. All
      the fractures healed without any complications. No evidence of avascular necrosis
      or arthritis was noted in our series. Subtrochanteric valgus osteotomy restores
      normal neck-shaft angle in patients suffering from FNSFs combined with coxa vara
      deformity. Moreover, it helps to bring the forces acting around the hip to normal
      biomechanical levels, leading to fracture union and better results. Replacement
      arthroplasty is recommended to patients who fail to achieve bony union after
      fixation.

PMID- 23540903
TI  - Pseudoarthrosis of medial tibial plateau fracture----role of alignment procedure.
AB  - Nonunion in tibial plateau fractures is very rare. Limited literature is
      available on Pubmed search on intraarticular tibial nonunion. Most of the cases
      reported have been following failed surgical treatment and none was neglected
      fractures. Three patients of isolated and neglected medial tibial plateau
      nonunion with almost similar demographic profile are reported in this paper. All
      the three patients were managed by minimally invasive compression fixation using
      lag screws supplemented with limb realignment procedure of high tibial osteotomy.
      We discussed the injury mechanism, management and rehabilitation in such cases
      and reviewed the available literature regarding such a presentation.

PMID- 23540904
TI  - Traumatic anterior hip dislocation in a 12-year-old child.
AB  - Hip dislocation in children can occur congenitally in isolation or in conjunction
      with other congenital abnormalities. Traumatic hip dislocations in children are
      relatively uncommon and anterior dislocation of hip joint is even rarer. We
      report such a case following unusual mode of injury in a 12-year-old child. The
      patient underwent successful emergent closed reduction of left hip. The clinical
      course and follow-up assessment of the patient was otherwise uneventful. At 2
      years' follow-up there was no evidence of osteoarthritis, coxa magna,
      heterotrophic calcification, in congruency of the joints or avascular necrosis of
      the head of femur.

PMID- 23540905
TI  - Simultaneous bilateral femoral neck fractures after electrical shock injury: a
      case report.
AB  - Simultaneous bilateral fractures of the femoral necks are rare injuries,
      especially when there is no underlying pathological condition. We report a 20
      year-old man who sustained bilateral femoral neck fractures resulting from an
      accidental electric shock with 440 V direct current. Simultaneous bilateral
      femoral neck fractures after electrical shock injury without falling from a
      height are rather uncommon in clinic. The main cause of the fracture may be
      muscle contraction. This case highlights that even in the absence of primary and
      secondary bone disease, bilateral fractures of the femoral necks can occur
      following electric shock injury. We successfully managed this case with bilateral
      cannulated screw fixation without bone grafting. Surgeons caring for patients
      with electrical injury should be aware of the possibility of skeletal injuries
      which can go unnoticed, leading to delay in diagnosis and increased risk of
      complications.

PMID- 23540906
TI  - Emergence of glass-like behavior in Markov state models of protein folding
      dynamics.
AB  - The extent to which glass-like kinetics govern dynamics in protein folding has
      been heavily debated. Here, we address the subject with an application of space
      time perturbation theory to the dynamics of protein folding Markov state models.
      Borrowing techniques from the s-ensemble method, we argue that distinct active
      and inactive phases exist for protein folding dynamics, and that kinetics for
      specific systems can fall into either dynamical regime. We do not, however,
      observe a true glass transition in any system studied. We go on to discuss how
      these inactive and active phases might relate to general protein folding
      properties.

PMID- 23540907
TI  - Ventral striatum binding of a dopamine D2/3 receptor agonist but not antagonist
      predicts normal body mass index.
AB  - BACKGROUND: Positron emission tomography research has shown that dopamine D2/3
      receptor (D2/3R) availability is negatively correlated with body mass index (BMI)
      in obese but not in healthy subjects. However, previous positron emission
      tomography studies have not looked specifically at the ventral striatum (VS),
      which plays an important role in motivation and feeding. Furthermore, these
      studies have only used antagonist radiotracers. Normal-weight rats given free
      access to high-fat diets demonstrate behavioral sensitization to D2/3R agonists
      but not to antagonists. Sensitization is associated with increased D2/3R
      affinity, which affects binding of agonists but not antagonists. METHODS: We
      examined the association between BMI within the nonobese range (18.6-27.8) and
      D2/3R availability in the VS with the use of the agonist radiotracer [(11)C]-(+)
      PHNO (n = 26) and the antagonist [(11)C]-raclopride (n = 35) in healthy humans.
      RESULTS: In the VS, we found a positive correlation between BMI and [(11)C]-(+)
      PHNO binding but no relationship with [(11)C]-raclopride binding. Secondary
      analyses revealed no relationship between BMI and binding in the dorsal striatum
      with either radiotracer. CONCLUSIONS: We propose that in nonobese individuals,
      higher BMI may be associated with increased D2R affinity in the VS. This
      increased affinity may potentiate the incentive salience of food cues and
      counteract the effects of satiety cues, thereby increasing feeding.

PMID- 23540909
TI  - Inhibitory control in childhood stuttering.
AB  - PURPOSE: The purpose of this study was to investigate whether previously reported
      parental questionnaire-based differences in inhibitory control (IC; Eggers, De
      Nil, & Van den Bergh, 2010) would be supported by direct measurement of IC using
      a computer task. METHOD: Participants were 30 children who stutter (CWS; mean
      age=7;05 years) and 30 children who not stutter (CWNS; mean age=7;05 years).
      Participants were matched on age and gender (+/-3 months). IC was assessed by the
      Go/NoGo task of the Amsterdam Neuropsychological Tasks (De Sonneville, 2009).
      RESULTS: Results indicated that CWS, compared to CWNS, (a) exhibited more false
      alarms and premature responses, (b) showed lower reaction times for false alarms,
      and (c) were less able to adapt their response style after experiencing response
      errors. CONCLUSIONS: Our findings provide further support for the hypothesis that
      CWS and CWNS differ on IC. CWS, as a group, were lower in IC pointing toward a
      lowered ability to inhibit prepotent response tendencies. The findings were
      linked to previous IC-related studies and to emerging theoretical frameworks of
      stuttering development. EDUCATIONAL OBJECTIVES: The reader will be able to: (1)
      describe the concept of inhibitory control, and its functional significance; (2)
      describe the findings on self-regulatory processes, attentional processes, and
      inhibitory control in CWS; (3) identify which Go/NoGo task variables
      differentiated between CWS and CWNS; and (4) summarize the theoretical
      implications for the development of stuttering and the possible clinical
      implications.

PMID- 23540908
TI  - Neural correlates of rapid antidepressant response to ketamine in treatment
      resistant unipolar depression: a preliminary positron emission tomography study.
AB  - BACKGROUND: Multiple lines of evidence support a role for the glutamatergic
      system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N
      methyl-D-aspartate antagonist, rapidly improves depressive symptoms in
      individuals with treatment-resistant depression. The neural mechanisms underlying
      this effect remain unknown. METHODS: In this preliminary study, 20 unmedicated
      participants with treatment-resistant MDD underwent positron emission tomography
      to measure regional cerebral glucose metabolism at baseline and following
      ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic
      data were compared between conditions using a combination of region-of-interest
      and voxelwise analyses, and differences were correlated with the associated
      antidepressant response. RESULTS: Whole-brain metabolism did not change
      significantly following ketamine. Regional metabolism decreased significantly
      under ketamine in the habenula, insula, and ventrolateral and dorsolateral
      prefrontal cortices of the right hemisphere. Metabolism increased postketamine in
      bilateral occipital, right sensorimotor, left parahippocampal, and left inferior
      parietal cortices. Improvement in depression ratings correlated directly with
      change in metabolism in right superior and middle temporal gyri. Conversely,
      clinical improvement correlated inversely with metabolic changes in right
      parahippocampal gyrus and temporoparietal cortex. CONCLUSIONS: Although
      preliminary, these results indicate that treatment-resistant MDD subjects showed
      decreased metabolism in the right habenula and the extended medial and orbital
      prefrontal networks in association with rapid antidepressant response to
      ketamine. Conversely, metabolism increased in sensory association cortices,
      conceivably related to the illusory phenomena sometimes experienced with
      ketamine. Further studies are needed to elucidate how these functional anatomical
      changes relate to the molecular mechanisms underlying ketamine's rapid
      antidepressant effects.

PMID- 23540910
TI  - The impact of stuttering on adults who stutter and their partners.
AB  - This study explored the impact of the stuttering disorder on perceived quality of
      life, with emphasis on the individual's relationship with their partner or
      spouse. Specifically, the purposes were: (a) to investigate what personal
      experiences and themes exist for both members of a couple dyad when one member of
      the couple stutters and (b) to examine whether the partners have different
      experiences with respect to the impact of stuttering on their lives. A mixed
      method research design was used. Participant dyads (adults who stutter and their
      fluent life partner) each completed one semi-structured qualitative interview and
      two questionnaires: the Overall Assessment of Speakers' Experience of Stuttering
      (OASES), and the Medical Short Form 36 (SF-36). Interviews were analysed
      qualitatively and significant themes evaluated. Quantitative results of the OASES
      and SF-36 were analysed, and scores correlated to determine the strength of any
      clinically significant relationships. Results indicated that people who stutter
      and their fluent partners reported similar experiences in reactions to stuttering
      and perceived difficulties in communication. However, no relationship was seen
      between the two groups in perceived impact on quality of life. Qualitative
      results indicated that the participants shared life experiences including
      reactions to stuttering, treatment undertaken and support. Such findings lend
      support to a broad-based clinical programme for adults who stutter that includes
      the fluent partner as an agent of change in their treatment. Findings also
      support the utilisation of qualitative and quantitative research techniques to
      elucidate relevant psychosocial life themes and experiences for those who live
      with a stutter. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) identify
      the life themes associated with having a partner who stutters; (b) identify the
      perceived impact of stuttering for adults who stutter compared to their partners;
      and (c) discuss the clinical implications of the results with regards to working
      with adults who stutter.

PMID- 23540911
TI  - Effects of sentence-structure complexity on speech initiation time and
      disfluency.
AB  - There is general agreement that stuttering is caused by a variety of factors, and
      language formulation and speech motor control are two important factors that have
      been implicated in previous research, yet the exact nature of their effects is
      still not well understood. Our goal was to test the hypothesis that sentences of
      high structural complexity would incur greater processing costs than sentences of
      low structural complexity and these costs would be higher for adults who stutter
      than for adults who do not stutter. Fluent adults and adults who stutter
      participated in an experiment that required memorization of a sentence classified
      as low or high structural complexity followed by production of that sentence upon
      a visual cue. Both groups of speakers initiated most sentences significantly
      faster in the low structural complexity condition than in the high structural
      complexity condition. Adults who stutter were over-all slower in speech
      initiation than were fluent speakers, but there were no significant interactions
      between complexity and group. However, adults who stutter produced significantly
      more disfluencies in sentences of high structural complexity than in those of low
      complexity. EDUCATIONAL OBJECTIVES: After reading this article, the learner will
      be able to: (a) identify integral parts of all well-known models of adult
      sentence production; (b) summarize the way that sentence structure might
      negatively influence the speech production processes; (c) discuss whether
      sentence structure influences speech initiation time and disfluencies.

PMID- 23540913
TI  - Bone graft sandwich osteotomy to correct a malpositioned dental implant.
AB  - As a result of inadequate planning, poor judgment, or losing one's orientation
      during surgery, implants may be placed in positions or at angulations that are
      less than ideal. The purpose of this report is to describe an alternative
      technique for the correction of a malpositioned osseointegrated implant by means
      of a maxillary anterior single implant segmental osteotomy associated with a
      'sandwich' bone graft technique. The technique described provides an alternative
      option for the surgeon faced with a malpositioned endosseous implant. It allows
      for a predictable result with preservation of the cervical gingival architecture,
      creates a more ideal environment for dental restoration, reduces treatment time
      compared to other techniques, and does so in a cost-effective manner.

PMID- 23540912
TI  - A preliminary investigation of phonological encoding skills in children who
      stutter.
AB  - PURPOSE: The present study investigated phonological encoding skills in children
      who stutter (CWS) and those who do not (CNS). Participants were 9 CWS (M=11.8
      years, SD=1.5) and 9 age and sex matched CNS (M=11.8 years, SD=1.5). METHOD:
      Participants monitored target phonemes located at syllable onsets and offsets of
      bisyllabic words. Performance in the phoneme monitoring task was compared to an
      auditory tone monitoring task. RESULTS: Repeated measures analysis of the
      response time data revealed significant Group*Task*Position interaction with the
      CWS becoming progressively slower than the CNS in monitoring subsequent phonemes
      located within the bisyllabic words; differences were not observed in the
      auditory tone monitoring task. Repeated measures analysis of the error data
      indicated that the groups were comparable in the percent errors in phoneme vs.
      tone monitoring. The CWS group was also significantly slower in a picture naming
      task compared to the CNS. CONCLUSIONS: Present findings suggest that CWS
      experience temporal asynchronies in one or more processes leading up to phoneme
      monitoring. The findings are interpreted within the scope of contemporary
      theories of stuttering. EDUCATIONAL OBJECTIVES: At the end of this activity the
      reader will be able to: (a) discuss the literature on phonological encoding
      skills in children who stutter, (b) identify theories of phonological encoding in
      stuttering, (c) define the process of phonological encoding and its implications
      for fluent speech, (d) suggest future areas of research in the investigation of
      phonological encoding abilities in children who stutter.

PMID- 23540914
TI  - Diastereoselective allylation of carbonyl compounds and imines: application to
      the synthesis of natural products.

PMID- 23540920
TI  - [Identification of patients at high risk of cancer after a venous thromboembolic
      disease].
AB  - OBJECTIVE: Assessment of cancer screening in the context of venous thromboembolic
      disease (VTE) remains controversial. We tried to characterize a population at
      high risk of developing cancer among patients suffering from VTE. METHOD: We
      conducted a retrospective ancillary case-control study among patients with VTE
      who later had a positive diagnosis of cancer. We assessed the association of
      cancer with characteristic features of VTE and with the results for four
      biological markers. RESULTS: Our population included 142 patients (53% men,
      median age 71 years). Two years after VTE, 24 patients (17%) had cancer. Median
      values for D-dimers, fibrin monomers and SP-selectin were significantly higher
      among patients who developed cancer. Logistic regression enabled us to identify
      two parameters targeting patients with a high risk of cancer: bilateral venous
      thrombosis (OR: 4.41, 95%CI: 1.41-13.78, P=0.01) and D-dimers superior to 3.8
      MUg/mL (OR: 3.68, 95%CI: 1.36-9.94, P=0.01). The information provided by these
      two characteristics was additive; 58% of patients in our population who had both
      factors developed cancer. CONCLUSION: Bilateral venous thrombosis and D-dimers
      superior to 3.8 MUg/mL are highly associated with carcinoma. This result requires
      a prospective validation. It could be useful in limiting the screening process to
      the population most at risk.

PMID- 23540921
TI  - Stabilization of the hexameric glutamate dehydrogenase from Escherichia coli by
      cations and polyethyleneimine.
AB  - The enzyme glutamate dehydrogenase (GDH) from Escherichia coli is a hexameric
      protein. The stability of this enzyme was increased in the presence of Li(+) in
      concentrations ranging from 1 to 10mM, 1M of sodium phosphate, or 1M ammonium
      sulfate. A very significant dependence of the enzyme stability on protein
      concentration was found, suggesting that subunit dissociation could be the first
      step of GDH inactivation. This effect of enzyme concentration on its stability
      was not significantly decreased by the presence of 10mM Li(+). Subunit
      crosslinking could not be performed using neither dextran nor glutaraldehyde
      because both reagents readily inactivated GDH. Thus, they were discarded as
      crosslinking reagents and GDH was incubated in the presence of polyethyleneimine
      (PEI) with the aim of physically crosslinking the enzyme subunits. This
      incubation does not have a significant effect on enzyme activity. However, after
      optimization, the PEI-GDH was found to almost maintain the full initial activity
      after 2h under conditions where the untreated enzyme retained only 20% of the
      initial activity, and the effect of the enzyme concentration on enzyme stability
      almost disappeared. This stabilization was maintained in the pH range 5-9, but it
      was lost at high ionic strength. This PEI-GDH composite was also much more stable
      than the unmodified enzyme in stirred systems. The results suggested that a real
      adsorption of the PEI on the GDH surface was required to obtain this stabilizing
      effect. A positive effect of Li(+) on enzyme stability was maintained after
      enzyme surface coating with PEI, suggesting that the effects of both stabilizing
      agents could not be exactly based on the same mechanism. Thus, the coating of GDH
      surface with PEI seems to be a good alternative to have a stabilized and soluble
      composite of the enzyme.

PMID- 23540922
TI  - A 1-step microplate method for assessing the substrate range of l-alpha-amino
      acid aminotransferase.
AB  - Aminotransferase enzymes catalyse the reversible substitution of a keto group for
      an amino group. While this reaction is highly stereoselective with respect to the
      amino group, each enzyme can usually catalyse the turnover of a number of
      different substrates. As the substrate range cannot be inferred from the
      sequence, it remains an early bottleneck when selecting an enzyme for a
      biocatalysis application. We have developed a simple first round characterisation
      method applicable to the broad range of aminotransferases that accept l
      glutamate, the central junction of cellular transamination, as one of the amino
      donors. The assay is based on l-glutamate detection by its highly specific
      dehydrogenase enzyme in a coupled assay, ending in the reduction of the 2,3-bis
      (2-methoxy-4-nitro-5-sulfophenyl)-tetrazolium-5-carboxanilide (XTT). While
      products of most tetrazolium salts are water-insoluble, XTT is reduced to a water
      soluble colored formazan, allowing direct spectrophotometric detection. The
      reaction is carried out in microplate format using a single endpoint measurement
      and is thus suitable for automation. The setup was tested with 7 aminotransferase
      enzymes: Escherichia coli branched chain amino acid aminotransferase, Pseudomonas
      aeruginosa and Klebsiella pneumoniae aromatic amino acid AT, Bacillus subtilis
      histidinol-phosphate AT, and Thermus aquaticus aspartate, serine and histidinol
      phosphate AT. In addition to 17 of the 20 proteinogenic amino acids, 32
      alternative substrates were tested.

PMID- 23540923
TI  - Kinetics of lipase recovery from the aqueous phase of biodiesel production by
      macroporous resin adsorption and reuse of the adsorbed lipase for biodiesel
      preparation.
AB  - A commercial macroporous resin (D3520) was screened for lipase recovery by
      adsorption from the aqueous phase of biodiesel production. The influences of
      several factors on the adsorption kinetics were investigated. It was found that
      the kinetic behavior of lipase adsorption by macroporous resin could be well
      described by pseudo-first-order model. Temperature had no significant effects on
      lipase adsorption, while resin-to-protein ratio (R) significantly affected both
      rate constant (k1) and equilibrium adsorption capacity (Qe). No lipase was
      adsorbed when mixing (shaking) was not performed; however, protein recovery
      reached 98% after the adsorption was conducted at 200rpm for 5h in a shaker. The
      presence of methanol and glycerol showed significant negative influence on lipase
      adsorption kinetics. Particularly, increasing glycerol concentration could
      dramatically decrease k1 but not impact Qe. Biodiesel was found to dramatically
      decrease Qe even present at a concentration as low as 0.02%, while k1 was found
      to increase with biodiesel concentration. The adsorbed lipase showed a relatively
      stable catalytic activity in tert-butanol system, but poor stability in solvent
      free system when used for biodiesel preparation. Oil and biodiesel were also
      found to adsorb onto resin during transesterification in solvent-free system.
      Therefore, the resin had to be washed by anhydrous methanol before re-used for
      lipase recovery.

PMID- 23540924
TI  - Characterization of sterol glucosyltransferase from Salinispora tropica CNB-440:
      potential enzyme for the biosynthesis of sitosteryl glucoside.
AB  - A sterol glucosyltransferase-encoded gene was isolated from Salinispora tropica
      CNB-440, a marine, sediment-dwelling, Gram positive bacterium that produces the
      potent anticancer compound, salinosporamide A. The full-length gene consists of
      1284 nucleotides and encodes 427 amino acids with a calculated mass of 45.65kDa.
      The gene was then cloned and heterologously expressed in Escherichia coli
      BL21(DE3). The amino acid sequence shares 39% similarity with the
      glycosyltransferase from Withania somnifera, which belongs to glycosyltransferase
      family 1. Enzyme reactions were carried out with the various free sterols
      (acceptor) and NDP-sugars (donor). The purified protein only showed activity for
      glucosylation of beta-sitosterol with UDP-D-glucose and TDP-D-glucose donors, and
      optimal activity at pH 7.5 and 37 degrees C. Among these two donors, UDP-D
      glucose was preferred.

PMID- 23540925
TI  - Fusion of cellulose binding domain from Trichoderma reesei CBHI to Cryptococcus
      sp. S-2 cellulase enhances its binding affinity and its cellulolytic activity to
      insoluble cellulosic substrates.
AB  - Cryptococcus sp. S-2 carboxymethyl cellulase (CSCMCase) is active in the acidic
      pH and lacks a binding domain. The absence of the binding domain makes the enzyme
      inefficient against insoluble cellulosic substrates. To enhance its binding
      affinity and its cellulolytic activity to insoluble cellulosic substrates,
      cellulose binding domain (CBD) of cellobiohydrolase I (CBHI) from Trichoderma
      reesei belonging to carbohydrate binding module (CBM) family 1 was fused at the C
      terminus of CSCMCase. The constructed fusion enzymes (CSCMCase-CBD and CSCMCase
      2CBD) were expressed in a newly recombinant expression system of Cryptococcus sp.
      S-2, purified to homogeneity, and then subject to detailed characterization. The
      recombinant fusion enzymes displayed optimal pH similar to those of the native
      enzyme. Compared with rCSCMCase, the recombinant fusion enzymes had acquired an
      increased binding affinity to insoluble cellulose and the cellulolytic activity
      toward insoluble cellulosic substrates (SIGMACELL((r)) and Avicel) was higher
      than that of native enzyme, confirming the presence of CBDs improve the binding
      and the cellulolytic activity of CSCMCase on insoluble substrates. This attribute
      should make CSCMCase an attractive applicant for various application.

PMID- 23540926
TI  - Pretreatment of sugarcane bagasse using supercritical carbon dioxide combined
      with ultrasound to improve the enzymatic hydrolysis.
AB  - This work evaluates the pretreatment of sugarcane bagasse combining supercritical
      carbon dioxide (SC-CO2) and ultrasound to enhance the enzymatic hydrolysis of
      pretreated bagasse. In a first step the influence of process variables on the SC
      CO2 pretreatment to enhance the enzymatic hydrolysis was evaluated by mean of a
      Plackett-Burmann design. Then, the sequential treatment combining ultrasound+SC
      CO2 was evaluated. Results show that treatment using SC-CO2 increased the amount
      of fermentable sugar obtained of about 280% compared with the non-treated
      bagasse, leading to a hydrolysis efficiency (based on the amount of cellulose) as
      high as 74.2%. Combining ultrasound+SC-CO2 treatment increased about 16% the
      amount of fermentable sugar obtained by enzymatic hydrolysis in comparison with
      the treatment using only ultrasound. From the results presented in this work it
      can be concluded that the combined ultrasound+SC-CO2 treatment is an efficient
      and promising alternative to carry out the pretreatment of lignocellulosic
      feedstock at relatively low temperatures without the use of hazardous solvents.

PMID- 23540927
TI  - Kinetic and thermodynamic analysis of the inhibitory effects of maltose, glucose,
      and related carbohydrates on wheat beta-amylase.
AB  - Inhibition of wheat beta-amylase (WBA) by glucose and maltose was studied by
      kinetics and thermodynamics. The inhibitory effects of fructose, difructose,
      sucrose, trehalose, cellobiose, acarbose, and 1-deoxynojirimycin on WBA were also
      evaluated. The half maximal inhibitory concentrations (IC50) of acarbose, maltose
      and glucose were 0.06+/-0.01M, 0.22+/-0.09M, and 1.41+/-0.17M, respectively. The
      inhibitor constant (Ki) and the thermodynamic parameters such as changes in Gibbs
      energy (DeltaG), enthalpy (DeltaH), and entropy (DeltaS) of the dissociation
      reactions of the WBA-glucose and WBA-maltose complexes were temperature and pH
      dependent. The dissociation reactions were endothermic and enthalpy-driven. Both
      glucose and maltose behaved as competitive inhibitors at pH 3.0 and 5.4 at a
      temperature of 25 degrees C with respective Ki values of 0.33+/-0.02M and 0.12+/
      0.03M. In contrast, both sugars exhibited uncompetitive inhibition at pH 9 at a
      temperature of 25 degrees C with Ki values of 0.21+/-0.03M for glucose and 0.11+/
      0.04M for maltose. The pH-dependence of the inhibition type and Ki values
      indicate that the ionizing groups of WBA influence drastically the interaction
      with these carbohydrates. This evidence enables us to consider temperature and pH
      in the WBA-catalyzed hydrolysis to manipulate the inhibition by end-product,
      maltose, and even by glucose.

PMID- 23540928
TI  - In vitro enzymatic conversion of gamma-aminobutyric acid immobilization of
      glutamate decarboxylase with bacterial cellulose membrane (BCM) and non-linear
      model establishment.
AB  - The work investigated the properties and feasibility of using bacterial cellulose
      membrane (BCM) as a new and environmental friendly support carrier to immobilize
      glutamate decarboxylase (GAD) (a unique enzyme in the conversion of gamma
      aminobutyric acid (GABA) production). During cultivation, the porosities of BCM
      decreased successively with more extended fibrils piling above one another in a
      criss-crossing manner thus forming condensed and spatial structure. The BCM with
      this ultrafine network structure was found to immobilize GAD best via covalent
      binding because of the highest efficiency of immobilization (87.56% of the enzyme
      was bonded) and a good operational stability. And the covalent binding efficiency
      (amount of enzyme immobilized versus lost) was closely related to the porosity or
      the inner network of the BCM, not to the surface area. The capacity per surface
      area (mg/cm(2)) increased from 1.267mg/cm(2) to 3.683mg/cm(2) when the porosity
      of BCM ranged from 49% to 73.80%, while a declining trend of the loss of GAD
      specific activity (from 29.30%/cm(2) to 7.38%/cm(2)) was observed when the
      porosity increased from 49.9% to 72.30%. Two non-linear regression relationships,
      between the porosity and loading capacity and between porosity and enzyme
      activity loss, were empirically modeled with the determination of coefficient
      R(2) of 0.980 and 0.977, respectively. Finally, the established in vitro
      enzymatic conversion process demonstrated 6.03g/L of GABA at 0.10mol/L Glu, 60min
      of retention time and 160mL of suspension volume after the 1st run and a loss of
      4.15% after the 4th run. The productivity of GABA was 6.03gL(-1)h(-1), higher
      than that from other reported processes.

PMID- 23540929
TI  - Immobilization of lysine oxidase on a gold-platinum nanoparticles modified Au
      electrode for detection of lysine.
AB  - A commercial lysine oxidase (LyOx) from Trichoderma viride was immobilized
      covalently onto gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs)
      electrodeposited onto Au electrode using 3-aminopropyltriethoxy silane (3-APTES)
      and glutaraldehyde cross linking chemistry. A lysine biosensor was fabricated
      using LyOx/3-APTES/AuNPs-PtNPs/Au electrode as a working electrode, Ag/AgCl (3M
      KCl) as standard electrode and Pt wire as auxiliary electrode connected through a
      potentiostat. The enzyme electrode was characterized by scanning electron
      microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, electrochemical
      impedance spectroscopy (EIS) and cyclic voltammetry (CV). The cumulative effect
      of AuNPs and PtNPs showed excellent electrocatalytic activity at low applied
      potential for detection of H2O2, a product of LyOx reaction. The sensor showed
      its optimum response within 4s, when polarized at 0.2V vs. Ag/AgCl in 0.1M
      phosphate buffer, pH 7.5 at 30 degrees C. The linear range and detection limit of
      the sensor were 1.0-600MUM and 1.0MUM (S/N=3), respectively. Biosensor measured
      lysine level in sera, milk and amino acid tablet, which correlated well with
      those by standard HPLC method. The enzyme electrode lost 50% of its initial
      activity after 200 uses over a period of 4 months.

PMID- 23540930
TI  - Screening of microbes for novel acidic cutinases and cloning and expression of an
      acidic cutinase from Aspergillus niger CBS 513.88.
AB  - Isolates from gardening waste compost and 38 culture collection microbes were
      grown on agar plates at pH 4.0 with the cutinase model substrate polycaprolactone
      as a carbon source. The strains showing polycaprolactone hydrolysis were
      cultivated in liquid at acidic pH and the cultivations were monitored by assaying
      the p-nitrophenyl butyrate esterase activities. Culture supernatants of four
      strains were analyzed for the hydrolysis of tritiated apple cutin at different
      pHs. Highest amounts of radioactive hydrolysis products were detected at pHs
      below 5. The hydrolysis of apple cutin by the culture supernatants at acidic pH
      was further confirmed by GC-MS analysis of the hydrolysis products. On the basis
      of screening, the acidic cutinase from Aspergillus niger CBS 513.88 was chosen
      for heterogeneous production in Pichia pastoris and for analysis of the effects
      of pH on activity and stability. The recombinant enzyme showed activity over a
      broad range of pHs with maximal activity between pH 5.0 and 6.5. Activity could
      be detected still at pH 3.5.

PMID- 23540931
TI  - Glycosylation site-targeted PEGylation of glucose oxidase retains native
      enzymatic activity.
AB  - Targeted PEGylation of glucose oxidase at its glycosylation sites was
      investigated to determine the effect on enzymatic activity, as well as the
      bioconjugate's potential in an optical biosensing assay. Methoxy-poly(ethylene
      glycol)-hydrazide (4.5kDa) was covalently coupled to periodate-oxidized
      glycosylation sites of glucose oxidase from Aspergillus niger. The bioconjugate
      was characterized using gel electrophoresis, liquid chromatography, mass
      spectrometry, and dynamic light scattering. Gel electrophoresis data showed that
      the PEGylation protocol resulted in a drastic increase (ca. 100kDa) in the
      apparent molecular mass of the protein subunit, with complete conversion to the
      bioconjugate; liquid chromatography data corroborated this large increase in
      molecular size. Mass spectrometry data proved that the extent of PEGylation was
      six poly(ethylene glycol) chains per glucose oxidase dimer. Dynamic light
      scattering data indicated the absence of higher-order oligomers in the PEGylated
      GOx sample. To assess stability, enzymatic activity assays were performed in
      triplicate at multiple time points over the course of 29 days in the absence of
      glucose, as well as before and after exposure to 5% w/v glucose for 24h. At a
      confidence level of 95%, the bioconjugate's performance was statistically
      equivalent to native glucose oxidase in terms of activity retention over the 29
      day time period, as well as following the 24h glucose exposure. Finally, the
      bioconjugate was entrapped within a poly(2-hydroxyethyl methacrylate) hydrogel
      containing an oxygen-sensitive phosphor, and the construct was shown to respond
      approximately linearly with a 220+/-73% signal change (n=4, 95% confidence
      interval) over the physiologically-relevant glucose range (i.e., 0-400mg/dL); to
      our knowledge, this represents the first demonstration of PEGylated glucose
      oxidase incorporated into an optical biosensing assay.

PMID- 23540932
TI  - Role of amine oxidase expression to maintain putrescine homeostasis in
      Rhodococcus opacus.
AB  - While applications of amine oxidases are increasing, few have been characterised
      and our understanding of their biological role and strategies for bacteria
      exploitation are limited. By altering the nitrogen source (NH4Cl, putrescine and
      cadaverine (diamines) and butylamine (monoamine)) and concentration, we have
      identified a constitutive flavin dependent oxidase (EC 1.4.3.10) within
      Rhodococcus opacus. The activity of this oxidase can be increased by over two
      orders of magnitude in the presence of aliphatic diamines. In addition, the
      expression of a copper dependent diamine oxidase (EC 1.4.3.22) was observed at
      diamine concentrations>1mM or when cells were grown with butylamine, which acts
      to inhibit the flavin oxidase. A Michaelis-Menten kinetic treatment of the flavin
      oxidase delivered a Michaelis constant (KM)=190MUM and maximum rate (kcat)=21.8s(
      1) for the oxidative deamination of putrescine with a lower KM (=60MUM) and
      comparable kcat (=18.2s(-1)) for the copper oxidase. MALDI-TOF and genomic
      analyses have indicated a metabolic clustering of functionally related genes.
      From a consideration of amine oxidase specificity and sequence homology, we
      propose a putrescine degradation pathway within Rhodococcus that utilises
      oxidases in tandem with subsequent dehydrogenase and transaminase enzymes. The
      implications of PUT homeostasis through the action of the two oxidases are
      discussed with respect to stressors, evolution and application in microbe
      assisted phytoremediation or bio-augmentation.

PMID- 23540933
TI  - Development of biosensor for phenolic compounds containing PPO in beta
      cyclodextrin modified support and iridium nanoparticles.
AB  - A biosensor based on the iridium nanoparticles dispersed in ionic liquid (IL) 1
      butyl-3-methylimidazolium hexafluorophosphate (Ir-BMI.PF6) and a celery (Apium
      graveolens) extract as a source of polyphenol oxidase (PPO) was constructed. A
      modified support based on beta-cyclodextrin (beta-CDEP) was used for enzyme
      immobilization. The behavior of phenolic compounds was investigated by square
      wave voltammetry and rutin was selected by presenting the greatest signal. The
      best performance was obtained with a composition of 70:10:10:10% (w/w/w/w) of the
      graphite powder:beta-CDEP:Nujol:Ir-BMI.PF6 composition, a PPO concentration of
      500unitsmL(-1), in 0.1M phosphate buffer solution (pH 6.0) with frequency, pulse
      amplitude and scan increment at 100Hz, 60mV, and 3.0mV, respectively. Under
      optimized conditions, the cathodic currents increased linearly for the rutin
      concentration range of 1.3*10(-7)-2.0*10(-6)M with a detection limit of 7.9*10(
      8)M. This sensor demonstrated acceptable repeatability and reproducibility and
      the results for the rutin recovery ranged from 92.8 to 103.4%. A relative error
      of 0.7% was obtained in the rutin determination in simulated samples.

PMID- 23540934
TI  - Alpha-mangostin and gambogic acid as potential inhibitors of the p53-MDM2
      interaction revealed by a yeast approach.
AB  - alpha-Mangostin (1) and gambogic acid (2) are natural products with potent
      cytotoxic activity against several human tumor cells. However, their molecular
      mechanisms of action remain controversial. In this work, using yeast-based
      assays, it was shown that both xanthones are potential inhibitors of the p53-MDM2
      interaction. This activity on p53-MDM2 interaction was confirmed by a gene
      reporter assay in a human tumor cell. Additionally, computational docking studies
      supported the potential of these xanthones to bind to MDM2 and therefore act as
      putative MDM2 inhibitors. Altogether, this work provides a new insight concerning
      the molecular basis of activity for these compounds. 

PMID- 23540935
TI  - Determinants of performance on the Transfer Task of the Basic Laparoscopic
      Urologic Surgery (BLUS((c))) curriculum administered at objective structured
      clinical examinations.
AB  - PURPOSE: To assess determinants of performance on the Transfer Task of the Basic
      Laparoscopic Urologic Surgery (BLUS((c))) skills curriculum administered at
      Objective Structured Clinical Examinations (OSCEs). METHODS: After obtaining
      Institutional Review Board approval and informed consent, urology trainees
      (Postgraduate Year [PGY]-3 to PGY-5) from four different training programs (A, B,
      C, D) were recruited for the study. Transfer Task Times (TTTs) were compared and
      correlated with previous laparoscopic experience, amount of endotrainer practice
      and scores obtained at practice sessions and other OSCE stations. RESULTS: A
      total of 37 trainees were evaluated on three successive semiannual OSCEs from May
      2011 to May 2012, including 16 (43.2%) trainees from program A with a dedicated
      laparoscopic skills training program. Compared with trainees from programs B, C,
      and D, trainees from program A had significantly more practice per week (0 v 45
      minutes, p=0.001) and significantly lower median TTTs at OSCEs (114 [68-209] v 74
      [52-189] seconds, p=0.001) despite significantly lower number of laparoscopic
      cases assisted within the previous 6 months (13 [0-57] v 2 [0-35], p=0.001). For
      program A trainees, TTTs moderately correlated with median TTTs at practice
      sessions (r=0.57, p=0.001) and negatively correlated with amount of practice per
      week (r=-0.41, p=0.003). Thus, more training resulted in faster times at OSCEs.
      On multivariate analysis, amount of practice per week was the only significant
      predictor of TTTs at OSCEs (p=0.028). CONCLUSION: Performance on the transfer
      task of BLUS during OSCEs significantly correlated with the amount of practice
      rather than the number of laparoscopic cases assisted.

PMID- 23540936
TI  - Early repolarization pattern: innocent finding or marker of risk?
AB  - The presence of early repolarization (ER) pattern in the 12-lead ECG, defined as
      elevation of the QRS-ST junction (J point) often associated with a late QRS
      slurring or notching (J wave), is a common finding in the general population,
      particularly in the inferior and precordial lateral leads. In young and healthy
      individuals, particularly in males, blacks and athletes, this pattern has
      commonly been considered to represent an innocent finding. However, experimental
      studies, case reports and studies on healthy subjects surviving a cardiac arrest
      or with primary ventricular fibrillation (VF) have suggested an association
      between J-point elevation and/or QRS slurring in the inferior and lateral ECG
      leads and the risk of VF. On the other hand, in recent epidemiological studies on
      large general population no significant association between ER patterns and
      cardiac mortality was found. In athletes, changes of the QRS-ST segment are
      frequent. We found that in a selected group of 21 young competitive athletes,
      without underlying heart disease, who experienced cardiac arrest, the prevalence
      of J wave and/or QRS slurring in the inferior and lateral (V4 to V6) leads was
      significantly higher in cases than in 365 control athletes. Following sport
      discontinuation, during the 36-month follow-up arrhythmia recurrences did not
      differ between subgroups with and without J wave or QRS slurring. Recently, other
      studies showed that among different patterns of ER rapidly ascending ST segment
      after the J point seems to be almost universally benign. The conflicting data
      regarding the prognostic role of ER patterns can be partly due to different
      definitions of ER used. This emphasizes the need for standardized methods of
      measurements of QRS end-J point-ST segment and for detailed definitions. The
      knowledge of the true significance in clinical setting of the various aspects of
      ER is still unclear and warrants prospective, long-term epidemiological studies. 

PMID- 23540938
TI  - Predictive DMPK: in silico ADME predictions in drug discovery.

PMID- 23540937
TI  - Localization of myocardial scar in patients with cardiomyopathy and left bundle
      branch block using electrocardiographic Selvester QRS scoring.
AB  - INTRODUCTION: Outcome of cardiac resynchronization therapy is severely worsened
      by myocardial scar at the left ventricular (LV) pacing site. We aimed to describe
      the diagnostic performance of electrocardiographic (ECG) criteria based on the
      Selvester QRS scoring system, first in localizing myocardial scar and second in
      screening for any non-septal scar in patients with strictly defined LBBB. METHODS
      AND RESULTS: In 39 cardiomyopathy patients with LBBB, 17 with scar, 22 without
      scar, late gadolinium-enhancement cardiac magnetic resonance images (CMR-LGE) and
      12-lead ECGs were analyzed for scar presence in 5 LV wall segments. The ECG
      criteria with the best diagnostic performance in detecting scar in each segment
      and in the four non-septal segments together were identified. Criteria for
      detecting non-septal scar had 75% (95% CI: 51%-90%) sensitivity, 95% (78%-99%)
      specificity, 92% (67%-99%) positive predictive value and 84% (65%-94%) negative
      predictive value. For each individual wall segment, 40%-60% sensitivities and 77%
      100% specificities were found. CONCLUSIONS: The 12-lead ECG can convey
      information about scar presence and location in this population of cardiomyopathy
      patients with LBBB. ECG screening criteria for scar in potential CRT LV pacing
      sites were identified. Further exploration is required to determine the clinical
      utility of the 12-lead ECG in combination with other imaging modalities to screen
      for scar in potential LV pacing sites in CRT candidates.

PMID- 23540939
TI  - Infection rates in patients undergoing primary knee arthroplasty with pre
      existing orthopaedic fixation-devices.
AB  - BACKGROUND: Prior knee surgery in the setting of knee arthroplasty (KA) can
      influence the overall outcome of the procedure and render the operation more
      technically challenging. The effects of residual fixation devices on subsequent
      procedures about the knee are ill-defined. Some authors claim an increase in
      periprosthetic infection in this cohort of patients. The objective of this study
      was to evaluate the overall incidence of periprosthetic infections in patients
      undergoing primary KA with pre-existing osteosynthetic hardware in situ. METHODS:
      The current investigators retrospectively reviewed 124 patients undergoing knee
      arthroplasty and removal of orthopaedic fixation devices, due to prior high
      tibial osteotomies, fracture fixation or cruciate ligament reconstruction. The
      exclusion criterion was a prior history of infection of the fixation device. The
      mean follow-up time was 5.4 years (range 15 months to 9 years). Nine patients
      were lost to follow-up. RESULTS: Joint aspiration was performed two weeks prior
      to surgery in 53 patients (42.4%) and intra-operative samples were obtained in
      106 patients (84.8%), which did not show any bacterial growth. A subacute
      periprosthetic infection occurred after seven months in only one patient.
      CONCLUSION: The results of the current study demonstrate that previously
      implanted osteosynthetic fixation devices do not significantly increase the risk
      of developing periprosthetic knee infections. A two-stage procedure with implant
      retrieval prior to total knee arthroplasty is not clinically indicated in the
      cohort described, amongst whom an infection rate of 0.9% was revealed.

PMID- 23540940
TI  - Estrogen-related receptor gamma and hearing function: evidence of a role in
      humans and mice.
AB  - Since estrogen is thought to protect pre-menopausal women from age-related
      hearing loss, we investigated whether variation in estrogen-signalling genes is
      linked to hearing status in the 1958 British Birth Cohort. This analysis
      implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult
      hearing function and was investigated further in a total of 6134 individuals in 3
      independent cohorts: (i) the 1958 British Birth Cohort; (ii) a London ARHL case
      control cohort; and (iii) a cohort from isolated populations of Italy and Silk
      Road countries. Evidence of an association between the minor allele of single
      nucleotide polymorphism (SNP) rs2818964 and hearing status was found in females,
      but not in males in 2 of these cohorts: p = 0.0058 (London ARHL) and p = 0.0065
      (Carlantino, Italy). Furthermore, assessment of hearing in Esrrg knock-out mice
      revealed a mild 25-dB hearing loss at 5 weeks of age. At 12 weeks, average
      hearing thresholds in female mice((-/-)) were 15 dB worse than in males((-/-)).
      Together these data indicate ESRRG plays a role in maintenance of hearing in both
      humans and mice.

PMID- 23540941
TI  - Measurements of medial temporal lobe atrophy for prediction of Alzheimer's
      disease in subjects with mild cognitive impairment.
AB  - Our aim was to compare the predictive accuracy of 4 different medial temporal
      lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive
      impairment (MCI). Manual hippocampal measurement, automated atlas-based
      hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle
      measurement were compared. Predictive accuracy for AD 2 years after baseline was
      assessed by receiver operating characteristics analyses with area under the curve
      as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years
      after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were
      investigated. Subjects with MCI were selected from the Development of Screening
      Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study
      (n = 156) and the single-center VU medical center (n = 172). At follow-up, area
      under the curve was highest for automated atlas-based hippocampal measurement
      (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65)
      and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal
      measurements correlated with CSF total tau and phosphorylated tau, not with beta
      amyloid 1-42. MTA-score and lateral ventricle volume correlated with CSF beta
      amyloid 1-42. We can conclude that volumetric hippocampal measurements are the
      best predictors of AD conversion in subjects with MCI.

PMID- 23540942
TI  - Nerve growth factor retrieves neuropeptide Y and cholinergic immunoreactivity in
      the nucleus accumbens of old rats.
AB  - The nucleus accumbens (NAc) contains high levels of neuropeptide Y (NPY), which
      is involved in the regulation of functions and behaviors that deteriorate with
      aging. We sought to determine if aging alters NPY expression in this nucleus and,
      in the affirmative, if those changes are attributable to the cholinergic
      innervation of the NAc. The total number and the somatic volume of NPY- and
      choline acetyltransferase-immunoreactive neurons, and the density of cholinergic
      varicosities were estimated in the NAc of adult (6 months old) and aged (24
      months old) rats. In aged rats, the number of NPY neurons was reduced by 20% and
      their size was unaltered. The number of cholinergic neurons and the density of
      the cholinergic varicosities were unchanged, but their somas were hypertrophied.
      Nerve growth factor administration to aged rats further increased the volume of
      cholinergic neurons, augmented the density of the cholinergic varicosities, and
      reversed the age-related decrease in the number of NPY neurons. Our data show
      that the age-related changes in NPY levels in the NAc cannot be solely ascribed
      to the cholinergic innervation of the nucleus.

PMID- 23540943
TI  - [Li(XeF2)n](AF6) (A = P, As, Ru, Ir), the first xenon(II) compounds of lithium.
      Synthesis, Raman spectrum, and crystal structure of [Li(XeF2)3](AsF6).
AB  - The reactions between compounds of the type MAF6 (M = alkali metal; A = P, As, V,
      Ru, Ir, Sb, Nb, Ta) and xenon difluoride were studied in anhydrous hydrogen
      fluoride solvent. The coordination products [M(XeF2)n]AsF6 were only observed in
      the case of LiAF6 (A = P, As, Ru, Ir), and the crystal structure of
      [Li(XeF2)3]AsF6 was determined (monoclinic space group P21 with a = 6.901(9) A, b
      = 13.19(2) A, c = 6.91(1) A, beta = 91.84(2) degrees , and Z = 2). The
      coordination sphere of lithium is comprised of six F atoms. The compound series
      was also characterized by Raman spectroscopy.

PMID- 23540944
TI  - Focal knee lesions in knee pairs of asymptomatic and symptomatic subjects with OA
      risk factors--data from the Osteoarthritis Initiative.
AB  - OBJECTIVE: To better understand the relationship between knee pain and bilateral
      knee lesions, we compared focal knee lesions in knee pairs of subjects with no,
      unilateral, and bilateral knee pain, and risk factors for knee osteoarthritis
      (OA), but no radiographic knee OA. MATERIALS AND METHODS: We examined both knees
      of 120 subjects from the Osteoarthritis Initiative database. We randomly selected
      60 subjects aged 45-55 years with OA risk factors, no knee pain (WOMAC pain
      score=0) and no radiographic OA (KL-score <=1) in both knees. We also selected
      two comparison groups with OA risk factors and no radiographic OA in both knees,
      but with knee pain (WOMAC pain score >=5): 30 subjects with right only knee pain
      and 30 subjects with bilateral knee pain. All subjects underwent 3T MRI of both
      knees and focal knee lesions were assessed. RESULTS: Statistically significant
      associations between prevalence of focal lesions in the right and left knee with
      odds ratios up to 13.5 were found in all three subject groups. Focal knee lesions
      were generally not associated with pain in analyses comparing knee pairs of
      subjects with unilateral knee pain (p>0.05). The prevalence and severity of focal
      knee lesions were not significantly different in knee pairs of subjects with no
      knee pain and those with bilateral knee pain (p>0.05). CONCLUSION: Focal knee
      lesions in the right and left knee of subjects with OA risk factors were
      positively associated with each other independent of knee pain status, and were
      not statistically significant different between knees in subjects with unilateral
      knee pain.

PMID- 23540945
TI  - Current status and perspectives of elastography.

PMID- 23540946
TI  - Is there different correlation with prognostic factors between "non-mass" and
      "mass" type invasive ductal breast cancers?
AB  - PURPOSE: To investigate the association between non-mass type breast cancer and
      common clinical-pathological prognostic factors, compared with mass type breast
      cancer. MATERIALS AND METHODS: After institutional review board approval,
      retrospective blind review of contrast-enhanced breast MRI was carried out for 88
      histologically proven breast invasive ductal carcinoma (IDC) patients, presenting
      from January 2008 to December 2011. Two radiologists assessed the images of each
      lesion for the morphologic enhancement type [mass enhancement or non-mass-like
      enhancement (NMLE)] and the distribution/internal enhancement of NMLE. Two
      pathologists evaluated the histological grade of IDC, presence or absence of
      ductal carcinoma in situ (DCIS), lymph node status, presence or absence of
      vascular invasion, and expression status of estrogen receptor (ER)/progesterone
      receptor (PR)/HER-2/p53 tumor suppressor gene (p53)/Ki-67. Inter-observer
      agreement was assessed with kappa test. Chi-square test and Spearman rank
      correlation were performed to explore the associations of morphologic enhancement
      type with the age, lesion size and the above pathological prognostic factors
      RESULTS: Inter-observer agreement was excellent, with kappa>0.75. Morphologic
      enhancement type was significantly correlated with age (P=0.02), with NMLE more
      commonly seen in women less than 50 y/o. The size of NMLE was larger than that of
      mass and, with the increase of lesion size, proportion of NMLE among the cases
      increased (P=0.001). NMLE was also significantly correlated with low histologic
      grade of IDC (P=0.003) and presence of DCIS (P<0.001). There was no significant
      correlation between morphologic enhancement type and lymph node status, vascular
      invasion, ER/PR/HER-2/p53/Ki-67 status. The histological grade was higher in
      clumped enhancement than non-clumped (P=0.011). There was no correlation between
      enhancement distribution and prognostic factors CONCLUSIONS: Non-mass type breast
      cancer may not necessarily have worse prognosis than the mass type, due to lower
      histological grade and closely related to DCIS component, although it may has
      larger tumor size. Clumped enhancement may have worse prognosis than non-clumped
      enhancement.

PMID- 23540947
TI  - Interobserver reliability of automated breast volume scanner (ABVS)
      interpretation and agreement of ABVS findings with hand held breast ultrasound
      (HHUS), mammography and pathology results.
AB  - OBJECTIVES: Handheld breast ultrasound (HHUS) lacks standardization and
      reproducibility. The automated breast volume scanner (ABVS) could overcome this
      limitation. To analyze the interobserver reliability of ABVS and the agreement
      with HHUS, mammography and pathology is the aim of this study. METHODS: All 42
      study participants (=84 breasts) received an ABVS examination in addition to the
      conventional breast diagnostic work-up. 25 breasts (30%) showed at least one
      lesion. The scans were interpreted by six breast diagnostic specialists blinded
      to results of breast imaging and medical history. 32 lesions received
      histological work-up: 20 cancers were detected. We used kappa statistics to
      interpret agreement between examiners and diagnostic instruments. RESULTS: On the
      basis of the Breast Imaging Reporting and Data System (BI-RADS) classification of
      the 84 breasts an agreement (defined as >=4 of 6 examiners) was achieved in 63
      cases (75%) (mk=0.35) and even improved when dichotomizing the interpretation in
      benign (BI-RADS 1, 2) and suspicious (BI-RADS 4, 5) to 98% (mk=0.52). Agreement
      of ABVS examination to HHUS, mammography and pathology was fair to substantial
      depending on the specific analysis. CONCLUSIONS: The development of an ABVS seems
      to be a promising diagnostic method with a good interobserver reliability, as
      well as a comparable good test criteria as HHUS.

PMID- 23540948
TI  - Simple rules for ultrasonographic subcategorization of BI-RADS(r)-US 4 breast
      masses.
AB  - OBJECTIVES: To evaluate an objective method for ultrasonographic (US)
      subcategorization of BI-RADS((r))-US 4 breast masses based on clear and simple
      rules in order for woman to benefit from a more complete and homogeneous breast
      mass analysis. METHODS: In this cross-sectional study, we selected 330 women,
      with 339 US breast masses, classified as BI-RADS((r))-US 4. Three physicians
      experienced in breast imaging independently reviewed all US images, assessing
      mass shape, margins, orientation, echo texture and vascularity. These experts
      further subdivided the masses into subcategories 4a, 4b and 4c, according to
      simple US rules. Inter-observer agreement was calculated for US features
      categories and for final subcategory assessment. We also estimated the positive
      predictive value (PPV) for BI-RADS((r))-US subcategories 4a, 4b and 4c assigned
      by each of the three observers. RESULTS: Pathological examination of all masses
      confirmed 144 (42%) malignant and 195 (58%) benign tumors. Moderate agreement was
      obtained for mass shape, margins, vascularity and for final BI-RADS((r))-US 4
      subcategory. Substantial agreement was obtained for the description of mass
      orientation and echo texture. The PPV for subcategories 4a, 4b and 4c were, 17%,
      45% and 85%, respectively, for the first observer and 20%, 38% and 79% and 17%,
      40% and 85% for the other two observers. CONCLUSION: Standardization of a US
      subcategorization of BI-RADS((r))-US 4 breast masses seems to be feasible, with
      substantial inter-observer agreement and progressive increase in the PPV in the
      subcategories 4a, 4b and 4c, provided that clear and simple classification rules
      are defined.

PMID- 23540949
TI  - An in vitro assessment of fibroblast and osteoblast response to alendronate
      modified titanium and the potential for decreasing fibrous encapsulation.
AB  - Fibrous encapsulation can impair implant osseointegration and cause implant
      failure but currently there are limited strategies to address this problem. Since
      bisphosphonates (BPs), a class of drugs widely used to treat bone diseases, was
      recently found to induce fibroblast apoptosis, we hypothesize that by loading BPs
      on titanium (Ti) implant surface, fibrous encapsulation may be inhibited with
      simultaneous enhancement of implant osseointegration. This strategy of local
      administration can also be expected to minimize the adverse side effects of BPs,
      which are associated with intravenous injections. To verify this hypothesis,
      alendronate was loaded on Ti surface via a hydroxyapatite (CaP) coating, and the
      effects of the loaded alendronate on fibroblast proliferation and apoptosis, and
      osteoblast proliferation, alkaline phosphatase (ALP) activity, and apoptosis were
      investigated in vitro. With a surface density of loaded alendronate 0.046
      mg/cm(2) or higher, fibroblast proliferation was suppressed due to increased
      apoptosis, while osteoblast proliferation and ALP activity increased with minimal
      apoptosis. In a coculture of fibroblasts and osteoblasts in a 1:1 ratio, ~60% of
      the cells on these alendronate-loaded substrates were osteoblasts 1 day after
      cell seeding. The percentage of osteoblasts increased to about 75% 4 days after
      cell seeding. These results suggest that fibroblasts and osteoblasts respond
      differently toward the alendronate-modified substrates, and this phenomenon can
      potentially be capitalized to reduce fibrous encapsulation.

PMID- 23540950
TI  - Sexual activity and aging.
AB  - Sexuality is an important component of emotional and physical intimacy that men
      and women experience throughout their lives. Research suggesting that a high
      proportion of men and women remain sexually active well into later life refutes
      the prevailing myth that aging and sexual dysfunction are inexorably linked. Age
      related physiological changes do not render a meaningful sexual relationship
      impossible or even necessarily difficult. Many of these physiological changes are
      modifiable. There are various therapeutic options available to patients to
      achieve maximum sexual capacity in old age. This article reviews the prevalence
      of sexual activity among older adults, the problems these adults encounter with
      sexual activity, and the role of the health care professional in addressing these
      problems. The physiological sex-related changes that occur as part of the normal
      aging process in men and women are reviewed, as well as the effect of age-related
      physical and psychological illness on sexual function. The attitudes and
      perceptions of the media and general public toward sexual activity and aging are
      summarized. An understanding of the sexual changes that accompany the aging
      process may help general practitioners and other doctors to give practical and
      useful advice on sexuality as well as refute the misconception that aging equates
      to celibacy. A thorough awareness of this aspect of older people's quality of
      life can raise meaningful expectations for aging patients. 

PMID- 23540951
TI  - Muscle strength rather than muscle mass is associated with standing balance in
      elderly outpatients.
AB  - OBJECTIVES: Assessment of the association of muscle characteristics with standing
      balance is of special interest, as muscles are a target for potential
      intervention (ie, by strength training). DESIGN: Cross-sectional study. SETTING:
      Geriatric outpatient clinic. PARTICIPANTS: The study included 197 community
      dwelling elderly outpatients (78 men, 119 women; mean age 82 years).
      MEASUREMENTS: Muscle characteristics included handgrip and knee extension
      strength, appendicular lean mass divided by height squared (ALM/height(2)), and
      lean mass as percentage of body mass. Two aspects of standing balance were
      assessed: the ability to maintain balance, and the quality of balance measured by
      Center of Pressure (CoP) movement during 10 seconds of side-by-side, semitandem,
      and tandem stance, with both eyes open and eyes closed. Logistic and linear
      regression models were adjusted for age, and additionally for height, body mass,
      cognitive function, and multimorbidity. RESULTS: Handgrip and knee extension
      strength, adjusted for age, were positively related to the ability to maintain
      balance with eyes open in side-by-side (P = .011; P = .043), semitandem (P =
      .005; P = .021), and tandem stance (P = .012; P = .014), and with eyes closed in
      side-by-side (P = .004; P = .004) and semitandem stance (not significant; P =
      .046). Additional adjustments affected the results only slightly. ALM/height(2)
      and lean mass percentage were not associated with the ability to maintain
      standing balance, except for an association between ALM/height(2) and tandem
      stance with eyes open (P = .033) that disappeared after additional adjustments.
      Muscle characteristics were not associated with CoP movement. CONCLUSION: Muscle
      strength rather than muscle mass was positively associated with the ability to
      maintain standing balance in elderly outpatients. Assessment of CoP movement was
      not of additional value.

PMID- 23540952
TI  - Direct admission to intermediate care for older adults with reactivated chronic
      diseases: avoiding both conventional hospitalization and emergency department
      use?

PMID- 23540953
TI  - European guidelines on upper tract urothelial carcinomas: 2013 update.
AB  - CONTEXT: The European Association of Urology (EAU) guideline group for upper
      tract urothelial carcinoma (UTUC) has prepared updated guidelines to aid
      clinicians in assessing the current evidence-based management of UTUC and to
      incorporate present recommendations into daily clinical practice. OBJECTIVE: To
      provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians in
      their daily clinical practice. EVIDENCE ACQUISITION: The recommendations provided
      in the current guidelines are based on a thorough review of available UTUC
      guidelines and articles identified using a systematic search of Medline. Data on
      urothelial malignancies and UTUCs in the literature were searched using Medline
      with the following keywords: urinary tract cancer; urothelial carcinomas; upper
      urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy;
      nephroureterectomy; adjuvant treatment; instillation; neoadjuvant treatment;
      recurrence; risk factors; nomogram; and survival. References were weighted by a
      panel of experts. EVIDENCE SYNTHESIS: There is a lack of data in the current
      literature to provide strong recommendations (ie, grade A) due to the rarity of
      the disease. A number of recent multicentre studies are now available, and there
      is a growing interest in UTUC in the recent literature. Overall, 135 references
      have been included here, but most of these studies are still retrospective
      analyses. The TNM 2009 classification is recommended. Recommendations are given
      for diagnosis as well as radical and conservative treatment (ie, imperative and
      elective cases); additionally, prognostic factors are discussed. Recommendations
      are also provided for patient follow-up after different therapeutic options.
      CONCLUSIONS: These guidelines contain information for the management of
      individual patients according to a current standardised approach. Physicians must
      take into account the specific clinical characteristics of each individual
      patient when determining the optimal treatment regimen including tumour location,
      grade, and stage; renal function; molecular marker status; and medical
      comorbidities.

PMID- 23540954
TI  - Impact of statin use on oncologic outcomes of patients with upper tract
      urothelial carcinoma treated with radical nephroureterectomy.

PMID- 23540955
TI  - Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein
      1 (VAP-1) inhibitors for the treatment of diabetic macular edema: part 2.
AB  - Novel thiazole derivatives were synthesized and evaluated as vascular adhesion
      protein-1 (VAP-1) inhibitors. Although our previous compound 1 showed potent VAP
      1 inhibitory activity, the activity differed between humans and rats. This issue
      was overcome by a hybrid design using human VAP-1 specific inhibitor 2, which was
      found by high-throughput screening (HTS), a docking study of a human VAP-1
      homology model, and an analysis of sequence information for humans and rats. As a
      result, we identified compound 35c, which showed strong VAP-1 inhibitory activity
      (human IC(50) of 20 nM; rat IC(50) of 72 nM) and significant inhibitory effects
      in the ex vivo test.

PMID- 23540956
TI  - Pre-ERCP imaging of the bile duct and gallbladder.
AB  - Advances in biliary imaging have improved making accurate diagnoses of the
      presence and causes of biliary obstruction. Abdominal ultrasound is a useful
      screening tool because it is highly specific for choledocholithiasis. New
      developments in CT and MRI have also been useful in the diagnosis of biliary
      disease. Although diagnosis of biliary disease can be achieved in a noninvasive
      manner, there are limitations to modern MRI and CT cholangiographic techniques;
      their use may not be necessary or cost effective. MRI and CT imaging of the
      biliary tract provides opportunities for less-invasive diagnostic techniques but
      should be used judiciously before interventional endoscopy.

PMID- 23540957
TI  - Infections of the biliary tract.
AB  - Infection of the biliary tract, or cholangitis, is a potentially life-threatening
      condition. Bile duct stones are the most common cause of biliary obstruction
      predisposing to cholangitis. The key components in the pathogenesis of
      cholangitis are biliary obstruction and biliary infection. Several underlying
      mechanisms of bactibilia have been proposed. Characteristic clinical features of
      cholangitis include abdominal pain, fever, and jaundice. A combination of
      clinical features with laboratory tests and imaging studies are frequently used
      to diagnose cholangitis. Endoscopic retrograde cholangiopancreatography is the
      best diagnostic test. Less invasive imaging tests may be performed initially in
      clinically stable patients with uncertain diagnoses.

PMID- 23540958
TI  - Difficult biliary access at ERCP.
AB  - Endoscopic retrograde cholangiopancreatography allows intervention for a variety
      of diseases of the biliary tract. Cannulation of the bile duct is the
      prerequisite step for biliary intervention. Although obtaining biliary access is
      straightforward in many cases, it can occasionally be challenging. Multiple
      devices, all with additional wire-guided techniques, have been developed to aid
      cannulation. More advanced techniques have also been developed to aid biliary
      access if it is unsuccessful with standard devices. Multimodality techniques can
      be used if other approaches fail. This article provides an evidence-based
      discussion of these approaches, and provides insight into their appropriate
      application.

PMID- 23540959
TI  - Choledochoscopy/cholangioscopy.
AB  - Miniature endoscopes that can be introduced into the bile duct through the
      duodenoscope during endoscopic retrograde cholangiopancreatography were developed
      to allow nonsurgical management of difficult biliary stones. The direct
      visualization enabled by these cholangioscopes of the biliary epithelium provides
      additional data in the assessment of biliary strictures. Cholangioscopy allows
      assessment of the biliary lumen, biliary epithelium, targeted tissue acquisition,
      targeted therapy, and wire guidance.

PMID- 23540960
TI  - Modern management of common bile duct stones.
AB  - It is imperative for gastroenterologists to understand the different formations
      of bile duct stones and the various medical treatments available. To minimize the
      complications of endoscopic retrograde cholangiopancreatography (ERCP), it is
      critical to appropriately assess the risk of bile duct stones before
      intervention. Biliary endoscopists should be comfortable with the basic
      techniques of stone removal, including sphincterotomy, mechanical lithotripsy,
      and stent placement. It is important to be aware of advanced options, including
      laser and electrohydraulic stone fragmentation, and papillary dilatation for
      problematic cases. The timing and need for ERCP in those who require a
      cholecystectomy is also a consideration.

PMID- 23540961
TI  - Endoscopic evaluation of bile duct strictures.
AB  - Differentiating between malignant and benign bile duct strictures is often
      challenging. Endoscopic retrograde cholangiopancreatography with brush cytology
      and/or endobiliary forceps biopsy is routinely performed. Advanced cytologic
      methods such as fluorescence in situ hybridization or digital image analysis
      increases the sensitivity of cytology. Endoscopic ultrasonography enables
      detailed examination of tissues surrounding the bile duct stricture and offers
      the advantage of fine-needle aspiration. Intraductal ultrasonography enables
      detailed evaluation of bile duct wall layers, and cholangioscopy offers direct
      visualization of the bile duct lesions. Novel techniques of probe-based confocal
      laser endomicroscopy and optical coherence tomography have introduced the era of
      in vivo histology.

PMID- 23540962
TI  - Endoscopic management of benign bile duct strictures.
AB  - The use of endoscopic retrograde cholangiopancreatography for treating benign
      biliary strictures has become the standard of practice, with surgery and
      percutaneous therapy reserved for selected patients. The gold-standard endoscopic
      therapy is dilation of the stricture followed by placing and exchanging
      progressively larger and more numerable plastic stents over a 1-year period.
      Newer modalities, including the use of fully covered metal stents, are currently
      under investigation in an effort to improve the treatment of benign biliary
      strictures.

PMID- 23540963
TI  - Endoscopic management of malignant bile duct strictures.
AB  - Malignant biliary obstruction can arise from intrahepatic, extrahepatic, and
      hilar locations from either primary or metastatic disease. Biliary-enteric
      surgical bypass has been surpassed in the last 20 years by endoscopic balloon
      dilation and stenting. The goal of stenting for biliary decompression is to
      palliate obstructive symptoms; it has not been shown that survival is affected by
      stenting alone. Novel endoscopic therapies, including photodynamic therapy and
      radiofrequency ablation, have been evaluated and show promise. Both therapies
      seem to be safe and effective in the treatment of malignant bile duct strictures
      but are in need of prospective studies of longer duration.

PMID- 23540964
TI  - Biliary manifestations of systemic diseases.
AB  - Patients with a variety of systemic diseases may present with clinical
      indications of biliary tract disorders. This article describes a group of
      systemic conditions associated with bile duct abnormalities and the role of
      endoscopic therapy in their diagnosis and management.

PMID- 23540965
TI  - Endoscopic approach to the patient with benign or malignant ampullary lesions.
AB  - Adenoma and adenocarcinoma are the most common ampullary lesions. Advances in
      diagnostic modalities including endoscopic ultrasonography and intraductal
      ultrasonography have provided useful information that aids in diagnosing and
      managing ampullary lesions. Endoscopic papillectomy can be a curative therapy for
      localized ampullary adenoma and have a role in the diagnosis of indeterminate
      ampullary lesions that may contain a hidden malignancy. However, the consensus on
      how and when to use endoscopic papillectomy has not been fully established. This
      article reviews the approach to the patient with benign or malignant ampullary
      lesion.

PMID- 23540966
TI  - Prevention and management of adverse events of endoscopic retrograde
      cholangiopancreatography.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is a therapeutic procedure
      with the potential for a variety of adverse events, including acute pancreatitis,
      perforation, bleeding, and cardiopulmonary complications, which are well
      established risk factors. It has become standard that patients undergoing ERCP
      are carefully selected based on appropriate indications. Once an ERCP is
      undertaken, preprocedure and intraprocedure risks should be assessed and
      appropriate risk-reducing modalities, such as prophylactic pancreatic stent
      placement and rectal indomethacin, should be used if patient or procedural
      factors suggest an increased risk of post-ERCP pancreatitis.

PMID- 23540967
TI  - Endoscopic approach to the patient with motility disorders of the bile duct and
      sphincter of Oddi.
AB  - Since its original description by Oddi in 1887, the sphincter of Oddi has been
      the subject of much study. Furthermore, the clinical syndrome of sphincter of
      Oddi dysfunction (SOD) and its therapy are controversial areas. Nevertheless, SOD
      is commonly diagnosed and treated by physicians. This article reviews the
      epidemiology, clinical manifestations, and current diagnostic and therapeutic
      modalities of SOD.

PMID- 23540968
TI  - Endoscopic ultrasonographic access and drainage of the common bile duct.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is currently the standard
      of care for biliary drainage. In the hands of experienced endoscopists,
      conventional ERCP has a failed cannulation rate of 3% to 5%. Failures have
      traditionally been referred for either percutaneous transhepatic biliary drainage
      (PTBD) or surgery. Both PTBD and surgery have higher than desirable complication
      rates. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a novel and
      attractive alternative after failed ERCP. Many groups have reported on the
      feasibility, efficacy, and safety of this technique. This article reviews the
      indications and technique currently practiced in EUS-BD, including EUS-guided
      rendezvous, EUS-guided choledochoduodenostomy, and EUS-guided
      hepaticogastrostomy.

PMID- 23540969
TI  - Endoscopic management of acute cholecystitis.
AB  - Acute cholecystitis is a commonly encountered medical emergency that is managed
      surgically with excellent results. Recent experiences with endoscopic cystic duct
      stent placement and cholecystectomy using the NOTES (Natural Orifice Transluminal
      Endoscopic Surgery) approach have inspired endoscopists to identify other less
      invasive means for treating cholecystitis. The ability to access and drain
      obstructive bile ducts in real time using endoscopic ultrasound guidance has led
      to recent reports of successful gallbladder drainage using similar techniques.
      This article discusses the current state of the endoscopic management of acute
      and acalculous cholecystitis, and outlines a consensus approach to the management
      of these patients.

PMID- 23540970
TI  - Endoscopic approach to the patient with bile duct injury.
AB  - Laparoscopic cholecystectomy (LC) is complicated by bile duct injury in 0.3% to
      0.6% of cases. These injuries range from simple leaks from the cystic duct stump
      that can almost always be managed by endoscopic stenting to complex strictures,
      transections, and even resections of the bile duct, often with concomitant
      vascular damage leading to ischemia. The management of LC-related biliary
      injuries requires a multidisciplinary approach involving an endoscopist
      experienced in the use of ERCP, a skilled interventional radiologist, and a
      surgeon with specific training in the management of hepatobiliary injuries.

PMID- 23540971
TI  - Endoscopic approach to the post liver transplant patient.
AB  - Biliary complications occur after liver transplantation. These complications can
      be effectively and safely managed using endoscopic approaches and can prevent
      unnecessary and potentially morbid surgery.

PMID- 23540972
TI  - Endoscopic approach to the bile duct in the patient with surgically altered
      anatomy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) in surgically altered
      anatomy can be technically challenging, because of three main problems that must
      be overcome: (1) endoscopically traversing the altered luminal anatomy, (2)
      cannulating the biliary orifice from an altered position, and (3) performing
      biliary interventions with available ERCP instruments. This article addresses the
      most common and most challenging variations in anatomy encountered by a
      gastroenterologist performing ERCP. It also highlights the innovations and
      progress that have been made in coping with these anatomic variations, with
      special attention paid to altered anatomy from bariatric surgery.

PMID- 23540973
TI  - Endoscopic approach to the patient with congenital anomalies of the biliary
      tract.
AB  - Congenital biliary tract anomalies typically present with neonatal cholestasis.
      In children and adults, endoscopic retrograde cholangiopancreatography (ERCP) and
      endoscopic ultrasound are used to evaluate and treat choledochal cysts.
      Contrarily, endoscopy has traditionally played a minor role in the diagnosis of
      the cholestatic infant. Recent studies support the incorporation of ERCP into the
      diagnostic algorithm for biliary atresia and neonatal cholestasis. But at
      present, most pediatric liver centers do not consider its use essential. This
      article reviews the congenital biliary tract anomalies in which endoscopy has
      been shown to contribute to the evaluation of the cholestatic infant.

PMID- 23540974
TI  - The best endoscopic methods in biliary disease.

PMID- 23540975
TI  - Endoscopic advances in biliary disease.

PMID- 23540976
TI  - Role of the left atrial function on the pseudonormalization of the transmitral
      flow velocity pattern evaluated by two-dimensional tissue tracking technique.
AB  - BACKGROUND: Mechanisms of the pseudonormalization (PN) of the transmitral flow
      (TMF) velocity pattern have been mainly attributed to left ventricular diastolic
      function. PURPOSE: To assess the influence of left atrial (LA) function on the PN
      with two-dimensional tissue tracking technique. METHODS: The subjects consisted
      of 21 healthy volunteers and 70 patients with various cardiac diseases. Images of
      one cardiac cycle in the apical four-chamber view were stored by the HIVISION 900
      (Hitachi Medico, Chiba, Japan). The LA volume (LAV) loop was created using two
      dimensional tissue tracking technique and LAV index (LAVI) at a given cardiac
      phase was calculated. A preload of 90mmHg was applied using a customized lower
      body positive pressure (LBPP) system. Patients were divided into the PN group
      (n=18) with their early diastolic TMF velocity (E) increased and late diastolic
      TMF velocity (A) decreased, and the non-(N)-PN group (n=52) with both E and A
      wave velocities increased by LBPP. RESULTS: (1) During LBPP, the LAVImax in both
      the groups increased significantly. (2) In the N-PN group, the LAVIpass
      (p<0.001), LAVIact (p<0.01), and LAVItotal (p<0.0001) increased significantly.
      The dV/dts (p<0.0001) and dV/dtE (p<0.0001) increased significantly with an
      increase in the dV/dtA. On the other hand, there was no change in those
      parameters except LAVIpass (p<0.05) and dV/dtE (p<0.05) significantly increased
      in the PN group. (3) As a result, the LAVImin was significantly greater in the PN
      group than in the N-PN group (p<0.0001) during LBPP. The ratio of E velocity to
      early diastolic mitral annular velocity (E/E') during LBPP was significantly
      greater in the PN group than in the N-PN group (p<0.0001). CONCLUSIONS: The lack
      of an increase in active LA emptying volume in response to an increase of preload
      leads to elevated LA pressure and the pseudonormalization of the TMF velocity
      pattern in patients with various cardiac diseases.

PMID- 23540978
TI  - Systematic review of the psychological consequences of false-positive screening
      mammograms.
AB  - BACKGROUND: In the UK, women aged 50-73 years are invited for screening by
      mammography every 3 years. In 2009-10, more than 2.24 million women in this age
      group in England were invited to take part in the programme, of whom 73% attended
      a screening clinic. Of these, 64,104 women were recalled for assessment. Of those
      recalled, 81% did not have breast cancer; these women are described as having a
      false-positive mammogram. OBJECTIVE: The aim of this systematic review was to
      identify the psychological impact on women of false-positive screening mammograms
      and any evidence for the effectiveness of interventions designed to reduce this
      impact. We were also looking for evidence of effects in subgroups of women. DATA
      SOURCES: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE,
      Health Management Information Consortium, Cochrane Central Register for
      Controlled Trials, Cochrane Database of Systematic Reviews, Centre for Reviews
      and Dissemination (CRD) Database of Abstracts of Reviews of Effects, CRD Health
      Technology Assessment (HTA), Cochrane Methodology, Web of Science, Science
      Citation Index, Social Sciences Citation Index, Conference Proceedings Citation
      Index-Science, Conference Proceeding Citation Index-Social Science and
      Humanities, PsycINFO, Cumulative Index to Nursing and Allied Health Literature,
      Sociological Abstracts, the International Bibliography of the Social Sciences,
      the British Library's Electronic Table of Contents and others. Initial searches
      were carried out between 8 October 2010 and 25 January 2011. Update searches were
      carried out on 26 October 2011 and 23 March 2012. REVIEW METHODS: Based on the
      inclusion criteria, titles and abstracts were screened independently by two
      reviewers. Retrieved papers were reviewed and selected using the same independent
      process. Data were extracted by one reviewer and checked by another. Each
      included study was assessed for risk of bias. RESULTS: Eleven studies were found
      from 4423 titles and abstracts. Studies that used disease-specific measures found
      a negative psychological impact lasting up to 3 years. Distress increased with
      the level of invasiveness of the assessment procedure. Studies using instruments
      designed to detect clinical levels of morbidity did not find this effect. Women
      with false-positive mammograms were less likely to return for the next round of
      screening [relative risk (RR) 0.97; 95% confidence interval (CI) 0.96 to 0.98]
      than those with normal mammograms, were more likely to have interval cancer [odds
      ratio (OR) 3.19 (95% CI 2.34 to 4.35)] and were more likely to have cancer
      detected at the next screening round [OR 2.15 (95% CI 1.55 to 2.98)].
      LIMITATIONS: This study was limited to UK research and by the robustness of the
      included studies, which frequently failed to report quality indicators, for
      example failure to consider the risk of bias or confounding, or failure to report
      participants' demographic characteristics. CONCLUSIONS: We conclude that the
      experience of having a false-positive screening mammogram can cause breast cancer
      specific psychological distress that may endure for up to 3 years, and reduce the
      likelihood that women will return for their next round of mammography screening.
      These results should be treated cautiously owing to inherent weakness of
      observational designs and weaknesses in reporting. Future research should include
      a qualitative interview study and observational studies that compare generic and
      disease-specific measures, collect demographic data and include women from
      different social and ethnic groups.

PMID- 23540979
TI  - Induction of specific immune responses in piglets by intramuscular immunization
      with fimbrial adhesin FaeG expressed in Lactococcus lactis.
AB  - Fimbrial adhesin plays a critical role in the pathogenesis of enterotoxigenic
      Escherichia coli (ETEC)-induced piglet diarrhoea. Lactococcus lactis is an
      attractive food-grade host for the production of heterologous antigens. We
      previously demonstrated that fimbrial adhesin FaeG was expressed in L. lactis and
      that oral immunization in mice with recombinant L. lactis expressing FaeG induced
      F4-specific mucosal and systemic immune responses. In the present study, we
      explored the immune responses of piglets induced by intramuscular vaccination
      with recombinant L. lactis expressing rFaeG. Intramuscular vaccination resulted
      in significantly elevated serum IgG level and modest increases in serum IgA and
      IgM levels. In addition, IgG, IgA, and IgM antibody secreting cells were induced
      in the spleen, mesenteric lymph nodes, and jejunum. The growth performance of
      piglets was not influenced by intramuscular vaccination. The results suggest that
      L. lactis expressing FaeG is a promising candidate vaccine against ETEC.

PMID- 23540980
TI  - Functional cellulose beads: preparation, characterization, and applications.

PMID- 23540981
TI  - Antioxidant lignans and chromone glycosides from Eurya japonica.
AB  - Four new 8,8',7,2'-lignans, (+)-ovafolinin B-9'-O-beta-d-glucopyranoside (1), (-)
      ovafolinin B-9'-O-beta-d-glucopyranoside (2), (+)-ovafolinin E-9'-O-beta-d
      glucopyranoside (3), and (-)-ovafolinin E-9'-O-beta-d-glucopyranoside (4), two
      neolignans, eusiderin N (5) and (7S,8R)-3,5,5'-trimethoxy-4',7-epoxy-8,3'
      neolignan-9,9'-diol-4-O-beta-d-xylopyranoside (6), and two new chromone
      glycosides, 5,7-dihydroxy-4H-chromen-4-one-3-O-beta-d-glucopyranoside (7) and 5,7
      dihydroxy-4H-chromen-4-one-3-O-beta-d-xylopyranoside (8), together with 25 known
      compounds, were isolated from the stems of Eurya japonica. Structural elucidation
      of compounds 1-8 was established by spectroscopic methods, especially 2D NMR
      techniques, electronic circular dichroism data, and comparison with reported
      data. The isolates were evaluated for antioxidant and anti-NO production
      activities. Compounds 1, 2, 12-20, and 29 (ED50 23.40 MUM for 1) demonstrated
      potent antioxidant activity compared to the positive control alpha-tocopherol
      (ED50 27.21 MUM). On the other hand, compounds 1, 2, 7-9, 12-20, and 32 showed
      only weak anti-NO production activity when compared to the positive control
      quercetin.

PMID- 23540982
TI  - Intra-operative breast volume estimation during breast reduction: validation of a
      commonly used technique.

PMID- 23540983
TI  - [Iberoamerica: lessons learned and good practices].

PMID- 23540984
TI  - [Postmenopausal osteoporosis: Primary prevention or excessive use of
      medications].
AB  - OBJECTIVE: [corrected] Estimate the percentage of excessive use of medicines
      (bisphosponates, strontium ranelate and raloxifene) in the prevention of
      fragility fractures in postmenopausal women. MATERIAL AND METHODS: A descriptive
      study conducted in an urban health centre in Vitoria-Gasteiz. The participants
      were women aged between 50 and 70, treated during 2010 with some of
      aforementioned medicines. Out of the 253 women included, three died, two moved,
      one did not want to sake part, and another one could not be found, leaving 246
      participants. It was determinated if the treatment was or not indicated, as
      recommended in the ESCEO, NAMS and NOF clinical practice guides. A data search,
      including fragility fracture history, densitometry performed, densitometry
      diagnoses, prescribed medicines and prescribing doctor, was carried out by
      looking in the Osabide and Global Clinic digital clinic records. Interviews were
      carried out with 72 patients for a more complete information. RESULTS: The mean
      patient age was 60.5 +/- 4.9 years, and 91,5% of them (225) had undergone a
      densitometry. Three-quarters (75.1%, 169) had a diagnosis of osteoporosis and
      4,4% (11) had previous history of fractures. More than a quarter (27.0%, 68) of
      treatments had no indication, and varied depending of the prescribing doctor
      (family doctors: 8.5%/ traumatologists: 58.5%) (p<0.001). The use of the medicine
      of choice, alendronate in 29.7% of cases, Was significantly higher (59.3%) in
      Primary Care than in other specialties. CONCLUSIONS: A high percentage of women
      are given excessive medication, exposing them to potentially severe secondary
      damages. Family doctors deal correctly with osteoporosis, with a high percentage
      of indicated treatments and a rational use of medicines, with alendronate as the
      first choice in the majority of cases.

PMID- 23540985
TI  - [Road safety in work commuting for primary care profesionals].
AB  - OBJECTIVE: To identify risk behavior patterns for basic health care professionals
      in road safety. Also to measure the incidence of road traffic accidents METHOD:
      Cross-sectional survey; population: complete Leon Area Basic Health Care team (N
      = 1048). Survey included different kind of variables: sociodemografic, labour,
      type of journey, road accidents going to work in the last three years and
      perceived risk; using a Likert scale people were asked about frequency of errors
      and driving offences (traffic offences). An bivariate analysis was made in order
      to study relationship between incidences and workers' characteristics with
      perceived risk. RESULTS: 54,3% of workers were analyzed. We found that 84.6% used
      the car as a means of transportation. Most common infraction declared were:
      driving after getting little sleep, speeding or being in a rush to get to work.
      Self-perceived risk as well as accident incidence is higher in nursing area
      workers, locum, those who travel more than 30km per day and those declared
      themselves as offenders. Accident incidence is 4.9% workers per year. CONCLUSION:
      Primary Health Care workers run high risk of accidents and it is well-perceived
      by them.

PMID- 23540986
TI  - [Prevalence of cardiovascular risk factors in Maghrebian immigrants in a
      semiurban area of Barcelona].
AB  - BACKGROUND: The cardiovascular risk factors present a high prevalence in our
      country, similar to other countries of the Mediterranean area. We don't know
      which is the distribution of these risk factors in the Maghrebian immigrant
      population. METHODS: There was designed a descriptive transverse study realized
      in 4 semiurban health center of Barcelona (Spain). 167 patients were included by
      means of consecutive sampling, between january 2005 and december 2006, major of
      age of a total population of 1127 Maghrebian assigned patients. There were
      studied the following cardiovascular risk factors: age, sex, smoking,
      hypercholesterolaemia, hypertriglyceridemia, high blood pressure and diabetes
      mellitus, and information was gathered as: time of stay in our country, weight,
      height, body mass index, the accomplishment of physical exercise, as well as
      precedents of isquemic cardiophaty. RESULTS: The middle ages were 36.79 years (SD
      11.42) and 59,88% they were men. The average time of stay in our country was 4
      years (P25-75, 2-6). The average IMC was of 26.96 (SD 5.21). 25.75% was smokers,
      22.75% obesity, 19.76% hypercholesterolaemia, 15.57% hypertriglyceridemia, 10.78%
      diabetes mellitus, 10.78% hypertension and 1.2% CI's precedents. The prevalence
      of cardiovascular risk factors was higher in women, with a significant difference
      in obesity, 35.82% by 14% (P <0.002), men had a higher prevalence of smoking, 40%
      from 4.48% in women (P <0.001). CONCLUSIONS: In our study the North African
      immigrant population has a prevalence of cardiovascular risk factors different
      from that obtained in population studies in Morocco, with a clear tendency to
      resemble the Spanish population of the host.

PMID- 23540987
TI  - [New oral anticoagulants in the treatment of venous thromboembolic disease].
AB  - Rivaroxaban is a direct inhibitor of activated factor X, and dabigatran is a
      direct inhibitor of thrombin. These new oral anticoagulants have demonstrated to
      be effective and safe in clinical trials on the treatment of venous
      thromboembolic disease (deep vein thrombosis and pulmonary thromboembolism).

PMID- 23540988
TI  - [Consensus on integrated care of acute exacerbations of chronic obstructive
      pulmonary disease (ATINA-EPOC). Part VII].

PMID- 23540989
TI  - [Consensus on integrated care of acute exacerbations of chronic obstructive
      pulmonary disease (ATINA-EPOC). Part VIII].

PMID- 23540990
TI  - [Home paracentesis in palliative care performed by primary care doctors:
      Presentation of a case].
AB  - Home paracentesis is a relatively simple and safe. Applied in the field of
      palliative home care by primary care physicians significantly increases patient
      comfort and gratitude from both patient and family, and avoids continuous visits
      to hospital emergency services to perform this technique on a regular basis. The
      patient is terminal, usually with pain, with distant metastases and multiple
      symptoms, where transfers by ambulance, waiting times, continuous admissions and
      discharges, have a big impact. We report a case of a patient with end-stage
      hepatocellular carcinoma in which we performed home paracentesis in collaboration
      with the palliative care support team of our hospital, with good results. Home
      monitoring by the primary care physician can help to improve both the care and
      the quality of life of these patients by increasing coordination between care
      levels and avoid hospital admissions.

PMID- 23540991
TI  - [Bilateral pelvic stress fracture].
AB  - A stress fracture is defined as that which occurs as a consequence of many low
      intensity traumas. These were originally described in the metatarsals of
      soldiers, and later on in athletes, and now we should consider them in general
      population subjected to excessive stress. Statistically, it generally occurs in
      women and in weight-bearing bones, such as the tibia, fibula and metatarsals.
      This case is of interest due to the diagnosis a double fracture in a woman
      without risk factors or increase in physical activity, and in an unusual location
      such as the pelvis. A detailed clinical history and examination are essential for
      the diagnosis.

PMID- 23540992
TI  - [Cervical adenocarcinoma as a rare cause of vaginal bleeding in a young woman].
AB  - Cervical adenocarcinoma is a less frequent variant than squamous carcinoma. The
      incidence of cervical adenocarcinoma has been increasing over the last several
      years. Villoglandular papillary adenocarcinoma usually affects young women and
      generally has a good prognosis. The treatment of this adenocarcinoma is surgical,
      with conisation being sufficient in localised cases, but a hysterectomy is often
      necessary to try and preserve the ovaries and maintain endocrine function.

PMID- 23540993
TI  - [Multiple familial osteochondromatosis: presentation of a case].
AB  - Enchondromas are benign cartilage tumours that grow slowly in the bone
      metaphysis. They may involve solitary or multiple lesions. Enchondromatoses
      include a heterogeneous group of hardly distinguishable syndromes characterised
      by the presence of multiple enchondromas that may cause musculoskeletal
      malformations (secondary to limb shortening), scoliosis, pathological fractures,
      or pseudoarthrosis. The most dreaded complication, osteochondrosarcoma, occurs in
      up to 25% of patients. We present the case of a 67-year-old male with no previous
      diagnosis, requiring attention due to the appearance of a painful tumour in his
      left hip which degenerated rapidly over the past year. Family history and
      clinical-radiological data confirmed the diagnosis of Multiple Familial
      Osteochondromatosis. Although clinical evolution and imaging led to suspect a
      malignant degeneration (osteochondrosarcoma), this was not confirmed by the
      histopathological study of the surgical sample.

PMID- 23540994
TI  - [Pulmonary thromboembolism in primary care].
AB  - The Primary Care physician must know the risk factors and to suspect the presence
      of a pulmonary thromboembolism (PTE) when there is a compatible clinical picture.
      We present two cases of a massive PTE in young healthy women in whom the taking
      of ethinylestradiol combined with cyproterone acetate was the only existing risk
      factor. We believe that the recommendations of the Spanish Medicines Agency
      should be followed and prescribe those contraceptives that have less than 30ug of
      ethinylestradiol and a second generation gestagen.

PMID- 23540995
TI  - [No rebels or objectors: 10 reasons to remember why you became a doctor].

PMID- 23540996
TI  - [Patient with nonspecific macular rash].

PMID- 23540997
TI  - Re: Does imaging modality used for percutaneous renal access make a difference? A
      matched case analysis. (From: Andonian S, Scoffone CM, Louie MK, et al. CROES
      PCNL Study Group. J Endourol 2013;27:24-28).

PMID- 23540998
TI  - Prognostic implications of NPM1 mutations and FLT3 internal tandem duplications
      in Egyptian patients with cytogenetically normal acute myeloid leukemia.
AB  - Nucleophosmin (NPM1) and fms-like tyrosine kinase 3-internal tandem duplication
      (FLT3-ITD) gene mutations represent the most frequent molecular aberrations in
      patients with cytogenetically normal-acute myeloid leukemia (CN-AML). We analyzed
      the prognostic impact of these mutations and their interactions in adults with CN
      AML. NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by
      polymerase chain reaction and GeneScan assays of bone marrow samples obtained
      from newly diagnosed 104 CN-AML patients. FLT3-ITD+ and NPM1mut were detected in
      36 (34.6%) and 30 (28.8%) out of 104 subjects, respectively, 16 cases (15.4%) had
      double NPM1mut/FLT3-ITD+. The incidence of FLT3-ITD+ was significantly higher in
      the NPM1mut group than in the NPM1 wild (NPM1wt) group (P = 0.018). Statistical
      analysis revealed that isolated NPM1mut group had a better clinical outcomes in
      terms of higher complete response (CR) rate (P = 0.01) and a trend towards
      favorable overall survival (OS) and disease-free survival (DFS) (P = 0.28, 0.40,
      respectively). In contrast, the isolated FLT3-ITD+ group had an unfavorable
      outcome in terms of lower CR rate (P = 0.12), shorter OS, and DFS (P < 0.0001 for
      both). The NPM1mut/FLT3-ITD-group had the best OS and DFS, while the NPM1wt/FLT3
      ITD+ group had the worst OS and DFS than other groups (NPM1mut/FLT3-ITD+ or
      NPM1wt/FLT3-ITD-) (P < 0.0001 for both). Multivariate Cox regression analysis
      showed that age and FLT3/ITD+ were independent poor prognostic factors for OS (P
      = 0.006, <0.0001, respectively), while FLT3/ITD+ was independent predictor for
      DFS (P = 0.04). However, NPM1mut did not have a significant impact on OS and DFS.
      In conclusion, adult patients with CN-AML carrying isolated NPM1mut and isolated
      FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+
      or NPM1wt/FLT3-ITD-. Patients with NPM1mut/FLT3-ITD- had the best prognosis in
      terms of higher CR, OS, and DFS, while those with NPM1mut/FLT3-ITD+ had the worst
      CR rate, and NPM1wt/FLT3-ITD+ had the lowest OS and DFS.

PMID- 23540999
TI  - Adolescents' domain-specific judgments about different forms of civic
      involvement: variations by age and gender.
AB  - Domain-specific judgments about different forms of civic engagement were assessed
      in a sample 467 primarily White adolescents (M age=15.26, range=11-19).
      Adolescents reported on the obligatory nature and social praiseworthiness
      (respect) of different forms of civic involvement. Adolescents distinguished
      among four different categories of civic involvement in their judgments:
      community service, standard political involvement (e.g., voting), social movement
      involvement (e.g., protesting), and community gathering activities. These mean
      differences were moderated by adolescent age (early, middle, and late
      adolescents) and gender. With increasing age, adolescents judged community
      service to be more worthy of respect but less obligatory. Compared to early
      adolescents, late adolescents prioritized standard political involvement as an
      activity in which US citizens should be engaged, but judged community gathering
      activities to be less obligatory. Across all age groups, girls judged community
      service and community gathering activities to be more obligatory than boys.

PMID- 23541001
TI  - Prenatal stress affects network properties of rat hippocampal neurons.
AB  - BACKGROUND: Long-term effects of stress during pregnancy on brain and behavior
      have been analyzed extensively in recent years. One major problem with these
      studies is the inability to separate between the net effects of the prenatal
      stress (PS) and the effects of the stressed mother and siblings on the newborn
      animals. METHODS: To address these issues, we studied morphological and
      electrophysiological properties of neurons in dissociated cultures of the
      hippocampus taken from newborn PS rats. We complemented these studies with
      experiments on behaving rats and recordings from slices taken from PS rats and
      their control rats. RESULTS: While the density of cultured neurons was not
      different between PS and control rats, there were fewer glutamic acid
      decarboxylase-positive neurons in the former cultures. Additionally, cells taken
      from PS pups developed more extensive dendrites than control animals. These
      differences were correlated with a higher rate of synchronous activity in the PS
      cultures and a lower rate of spontaneous miniature inhibitory postsynaptic
      current activity. There were no differences in the excitatory synaptic currents
      or the passive and active properties of the recorded neurons in the two groups.
      Young PS rats were more motile in open field and elevated plus maze than control
      rats, and they learned faster to navigate in a water maze. Slices taken from
      hippocampus of PS rats expressed less paired-pulse inhibition than slices from
      control rats. CONCLUSIONS: These results indicate that PS affects network
      properties of hippocampal neurons, by reducing gamma-aminobutyric acidergic
      inhibition.

PMID- 23541002
TI  - What is the best airway clearance technique in cystic fibrosis?
AB  - The global development of airway clearance techniques (ACTs) for cystic fibrosis
      (CF) and corresponding research spans over four decades. Five Cochrane reviews
      synthesising the evidence from a plethora of early short and medium term studies
      have not uncovered any superior method. Four recent long term RCT studies exposed
      fundamental shortcomings in the standard RCT trial design and the insensitivity
      of FEV1 in physiotherapy studies. Strong patient preference, lack of blinding and
      the requirement for effortful and demanding participation over long intervals
      will continue to derail efforts to find the best ACT for CF, unless they are
      addressed in future clinical trials.

PMID- 23541000
TI  - Stress as a common risk factor for obesity and addiction.
AB  - Stress is associated with obesity, and the neurobiology of stress overlaps
      significantly with that of appetite and energy regulation. This review will
      discuss stress, allostasis, the neurobiology of stress and its overlap with
      neural regulation of appetite, and energy homeostasis. Stress is a key risk
      factor in the development of addiction and in addiction relapse. High levels of
      stress changes eating patterns and augments consumption of highly palatable (HP)
      foods, which in turn increases incentive salience of HP foods and allostatic
      load. The neurobiological mechanisms by which stress affects reward pathways to
      potentiate motivation and consumption of HP foods as well as addictive drugs is
      discussed. With enhanced incentive salience of HP foods and overconsumption of
      these foods, there are adaptations in stress and reward circuits that promote
      stress-related and HP food-related motivation as well as concomitant metabolic
      adaptations, including alterations in glucose metabolism, insulin sensitivity,
      and other hormones related to energy homeostasis. These metabolic changes in turn
      might also affect dopaminergic activity to influence food motivation and intake
      of HP foods. An integrative heuristic model is proposed, wherein repeated high
      levels of stress alter the biology of stress and appetite/energy regulation, with
      both components directly affecting neural mechanisms contributing to stress
      induced and food cue-induced HP food motivation and engagement in overeating of
      such foods to enhance risk of weight gain and obesity. Future directions in
      research are identified to increase understanding of the mechanisms by which
      stress might increase risk of weight gain and obesity.

PMID- 23541004
TI  - QT prolongation and mortality in hospital settings: identifying patients at high
      risk.

PMID- 23541003
TI  - The matrikine tenascin-C protects multipotential stromal cells/mesenchymal stem
      cells from death cytokines such as FasL.
AB  - Multipotential stromal cells/mesenchymal stem cells (MSCs) are attractive
      candidates for regenerative therapy due to the ability of these cells to
      differentiate and positively influence neighboring cells. However, on
      implantation for wound reconstruction, these cells are lost as they are
      challenged by nonspecific inflammation signals generated in the wound environment
      and in response to any implanted foreign body. We have previously shown that
      sustained and surface-restricted epidermal growth factor receptor (EGFR)
      signaling by a tethered form of its prototypal ligand EGF enhances survival of
      MSC in the presence of death cytokines such as FasL, serum deprivation, and low
      oxygen in vitro. This was proposed to be due to the plasma membrane restriction
      of EGFR signaling. Interestingly, during wound repair, an extracellular matrix
      (ECM) component Tenascin-C (TNC) containing EGF-like repeats (EGFL) and
      fibronectin-like repeats (FNL) is upregulated. A few of the 14 EGFL on each of
      the 6 arms, especially the 14th, bind as low-affinity/high-avidity ligands to
      EGFR causing sustained surface-restricted EGFR signaling. We queried whether
      signaling by this physiologically relevant EGFR matrikine also protects MSCs from
      FasL-induced death. MSCs grown on TNC and Collagen I (as TNC by itself is
      antiadhesive) displayed a survival advantage in the presence of FasL. TNC neither
      sequestered nor neutralized FasL; rather, the effects of survival were via cell
      signaling. This survival was dependent on TNC activating EGFR and downstream
      pathways of Erk and Akt through EGFL; to a much lesser extent, the FNL of TNC
      also contributed to survival. Taken together, these results suggest that
      providing MSCs with a nonimmunogenic naturally occurring ECM moiety such as TNC
      enhances their survival in the presence of death factors, and this advantage
      occurs via signaling through EGFR primarily and integrins only to a minor extent.
      This matrix component is proposed to supplement MSC delivery on the scaffolds to
      provide a survival advantage against death upon in vivo implantation. 

PMID- 23541005
TI  - Does electroencephalography provide a "window to the brain" for the
      neurologically ill?

PMID- 23541006
TI  - Institution-wide QT alert system identifies patients with a high risk of
      mortality.
AB  - OBJECTIVES: To determine the phenotype and outcome of patients with QTc of at
      least 500 ms and to create a pro-QTc risk score for mortality. PATIENTS AND
      METHODS: An institution-wide computer-based QT alert system was developed and
      implemented at Mayo Clinic in Rochester, Minnesota. This system screens all
      electrocardiograms (ECGs) performed and alerts the physician if the QTc is 500 ms
      or greater. Between November 10, 2010, and June 30, 2011, 86,107 ECGs were
      performed in 52,579 patients. Clinical diagnoses, laboratory abnormalities, and
      medications known to influence the QT interval were collected from the medical
      records and summarized in a new pro-QTc score. Survival was compared with that of
      the 51,434 Mayo Clinic patients with a QTc less than 500 ms during the same
      period. RESULTS: QT alerts were sent for 1145 patients (2%); of these, 470 (41%)
      had no other identifiable ECG reason for QT prolongation (eg, pacing). All-cause
      mortality during a mean +/- SD of 224 +/- 174 days of follow-up was 19% in those
      with QTc of 500 ms or greater compared with 5% in patients with QTc less than 500
      ms (log-rank P<.001). The pro-QTc score was an age-independent predictor of
      mortality (pro-QTc score: hazard ratio, 1.18; 95% CI, 1.05-1.32; P=.006; age:
      hazard ratio, 1.02; 95% CI, 1.01-1.03; P=.004.). QT-prolonging medications
      accounted for 37% of the pro-QTc score. CONCLUSION: This novel institution-wide
      QT alert system identified patients with a high risk of mortality. The pro-QTc
      score, reflecting patients' multimorbidity and multipharmacy, was an independent
      predictor of mortality. The QT alert system may increase a physician's awareness
      of a high-risk patient. Potentially lifesaving interventions can be facilitated
      by reducing the modifiable factors of the pro-QTc score.

PMID- 23541007
TI  - Diagnostic yield of electroencephalography in a general inpatient population.
AB  - OBJECTIVE: To determine the frequency and clinical predictors of seizures and
      markers of epileptiform activity in a non-critically ill general inpatient
      population. PATIENTS AND METHODS: We performed a retrospective cohort study of
      patients 18 years and older who underwent inpatient electroencephalography (EEG)
      between January 1, 2005, and December 31, 2010, for an indication of spells or
      altered mental status. The EEGs and reports were reviewed for ictal activity,
      interictal epileptiform abnormalities, and nonepileptiform abnormalities.
      Demographic and clinical data were gathered from the electronic medical record to
      determine seizure predictors. RESULTS: Of 2235 patients screened, 1048 met the
      inclusion criteria, of which 825 (78.7%) had an abnormal EEG finding. Seizures
      occurred in 78 of 1048 patients (7.4%), and interictal epileptiform discharges
      were noted in 194 of 1048 patients (18.5%). An intracranial mass and spells as
      the indication for the EEG were independently associated with the group of
      patients experiencing seizures in a multivariate logistic regression model
      (adjusted for age, sex, EEG indication, intracranial mass, stroke, and history of
      epilepsy). Ninety-seven percent of patients (69 of 71) experienced their first
      seizure within 24 hours of monitoring, and the presence of seizures was
      associated with a lower likelihood of being discharged (odds ratio, 0.45; 95% CI,
      0.27-0.76). CONCLUSION: Seizures occurred at a high frequency in hospitalized
      patients with spells and altered mental status. The EEG may be an underused
      investigative tool in the hospital with the potential to identify treatable
      causes of these common disorders.

PMID- 23541008
TI  - Prognostic importance of risk factors for temporal lobe epilepsy in patients
      undergoing surgical treatment.
AB  - OBJECTIVE: To investigate the prognostic importance of an identified putative
      underlying risk factor in patients undergoing surgery for intractable temporal
      lobe epilepsy (TLE). PATIENTS AND METHODS: A retrospective study of 400
      consecutive patients who underwent TLE surgery between December 21, 1987, and
      September 11, 1996, was performed. Demographic characteristics, history of remote
      symptomatic neurologic disease, preoperative evaluation, and postoperative
      outcome data were extracted. Individuals without any risk factors were considered
      controls. Magnetic resonance imaging findings were used to identify mesial
      temporal sclerosis (MTS) before surgery. Seizure outcome was classified by a
      modified Engel classification. RESULTS: Two hundred eighty-one patients had a
      potential underlying etiology, and 143 patients had more than 1 risk factor. One
      hundred nineteen patients had no evidence of a putative symptomatic neurologic
      illness. There was a statistically significant association (P<.05) between the
      presence of MTS and a favorable operative outcome (odds ratio, 4.28; 95% CI, 2.67
      6.87). A history of remote symptomatic neurologic disease was not of prognostic
      importance unless associated with the development of MTS. CONCLUSION: These
      results indicate that the preoperative identification of MTS by neuroimaging is
      the most important predictor of a favorable operative outcome in patients with
      TLE. These findings may be useful in the identification and counseling of
      potential candidates for epilepsy surgery.

PMID- 23541009
TI  - Population-based study of the use of cardiac stress imaging and referral for
      coronary angiography and repeated revascularization after coronary artery bypass
      graft surgery.
AB  - OBJECTIVE: To assess stress single-photon emission computed tomography (SPECT)
      and stress echocardiography use after coronary artery bypass grafting (CABG) and
      their effect on referral for coronary angiography and revascularization. PATIENTS
      AND METHODS: The referral, timing, and results of stress imaging after CABG;
      referral for coronary angiography and revascularization; and all-cause mortality
      were assessed in this longitudinal, population-based, retrospective study of 1138
      Olmsted County, Minnesota, patients undergoing CABG between January 1, 1993, and
      December 31, 2003. RESULTS: A total of 570 patients (50.1%) underwent a stress
      imaging study (341 SPECT and 229 echocardiography) during the study period. Of
      the 1138 patients, 372 (32.7%) were referred for coronary angiography, and 144 of
      those patients (12.7%) underwent repeated revascularization (132 percutaneous
      revascularization and 12 CABG). The median interval between CABG and the index
      stress imaging study was 3.0 years (25th-75th percentile, 1.2-5.7 years). The
      results of 75.7% (258 of 341) of the stress SPECT studies and 70.7% (162 of 229)
      of the stress echocardiograms were abnormal. Seventy-six of 570 patients (13.3%)
      referred for stress imaging underwent coronary angiography within 180 days after
      the stress test. Repeated coronary revascularization was performed in 25 patients
      (4.4%) who underwent a stress imaging study within the preceding 180 days. The 5-
      and 10-year survival rates in the entire study cohort (83.5% and 65.1%,
      respectively) were not significantly different than predicted for the age- and
      sex-matched Minnesota population. CONCLUSION: Half of this community-based
      population of patients with CABG underwent stress SPECT or echocardiography
      during median follow-up of 8.9 years. Despite that approximately 75% of the
      results of stress imaging studies were abnormal, subsequent referral for coronary
      angiography within 180 days was low (13.3%), and the yield for repeated
      revascularization was very low (4.4%).

PMID- 23541010
TI  - Computerized bar code-based blood identification systems and near-miss
      transfusion episodes and transfusion errors.
AB  - OBJECTIVE: To determine whether the use of a computerized bar code-based blood
      identification system resulted in a reduction in transfusion errors or near-miss
      transfusion episodes. PATIENTS AND METHODS: Our institution instituted a
      computerized bar code-based blood identification system in October 2006. After
      institutional review board approval, we performed a retrospective study of
      transfusion errors from January 1, 2002, through December 31, 2005, and from
      January 1, 2007, through December 31, 2010. RESULTS: A total of 388,837 U were
      transfused during the 2002-2005 period. There were 6 misidentification episodes
      of a blood product being transfused to the wrong patient during that period
      (incidence of 1 in 64,806 U or 1.5 per 100,000 transfusions; 95% CI, 0.6-3.3 per
      100,000 transfusions). There was 1 reported near-miss transfusion episode
      (incidence of 0.3 per 100,000 transfusions; 95% CI, <0.1-1.4 per 100,000
      transfusions). A total of 304,136 U were transfused during the 2007-2010 period.
      There was 1 misidentification episode of a blood product transfused to the wrong
      patient during that period when the blood bag and patient's armband were scanned
      after starting to transfuse the unit (incidence of 1 in 304,136 U or 0.3 per
      100,000 transfusions; 95% CI, <0.1-1.8 per 100,000 transfusions; P=.14). There
      were 34 reported near-miss transfusion errors (incidence of 11.2 per 100,000
      transfusions; 95% CI, 7.7-15.6 per 100,000 transfusions; P<.001). CONCLUSION:
      Institution of a computerized bar code-based blood identification system was
      associated with a large increase in discovered near-miss events.

PMID- 23541011
TI  - Management of newly diagnosed symptomatic multiple myeloma: updated Mayo
      Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines
      2013.
AB  - Multiple myeloma remains an incurable neoplasm of plasma cells that affects more
      than 20,000 people annually in the United States. There has been a veritable
      revolution in this disease during the past decade, with dramatic improvements in
      our understanding of its pathogenesis, the development of several novel agents,
      and a concomitant doubling in overall survival. Because multiple myeloma is a
      complex and wide-ranging disorder, its management must be guided by disease- and
      patient-related factors; emerging as one of the most influential factors is risk
      stratification, primarily based on cytogenetic features. A risk-adapted approach
      provides optimal therapy to patients, ensuring intense therapy for aggressive
      disease and minimizing toxic effects, providing sufficient but less intense
      therapy for low-risk disease. This consensus statement reflects recommendations
      from more than 20 Mayo Clinic myeloma physicians, providing a practical approach
      for newly diagnosed patients with myeloma who are not enrolled in a clinical
      trial.

PMID- 23541013
TI  - Atrial fibrillation in the 21st century: a current understanding of risk factors
      and primary prevention strategies.
AB  - Atrial fibrillation (AF) is the most common arrhythmia worldwide, and it has a
      significant effect on morbidity and mortality. It is a significant risk factor
      for stroke and peripheral embolization, and it has an effect on cardiac function.
      Despite widespread interest and extensive research on this topic, our
      understanding of the etiology and pathogenesis of this disease process is still
      incomplete. As a result, there are no set primary preventive strategies in place
      apart from general cardiology risk factor prevention goals. It seems intuitive
      that a better understanding of the risk factors for AF would better prepare
      medical professionals to initially prevent or subsequently treat these patients.
      In this article, we discuss widely established risk factors for AF and explore
      newer risk factors currently being investigated that may have implications in the
      primary prevention of AF. For this review, we conducted a search of PubMed and
      used the following search terms (or a combination of terms): atrial fibrillation,
      metabolic syndrome, obesity, dyslipidemia, hypertension, type 2 diabetes
      mellitus, omega-3 fatty acids, vitamin D, exercise toxicity, alcohol abuse, and
      treatment. We also used additional articles that were identified from the
      bibliographies of the retrieved articles to examine the published evidence for
      the risk factors of AF.

PMID- 23541014
TI  - 69-year-old man with recurrent episodes of confusion and diaphoresis.

PMID- 23541012
TI  - My approach to the treatment of scleroderma.
AB  - Systemic sclerosis (scleroderma) is unique among the rheumatic diseases because
      it presents the challenge of managing a chronic multisystem autoimmune disease
      with a widespread obliterative vasculopathy of small arteries that is associated
      with varying degrees of tissue fibrosis. The hallmark of scleroderma is clinical
      heterogeneity with subsets that vary in the degree of disease expression, organ
      involvement, and ultimate prognosis. Thus, the term scleroderma is used to
      describe patients who have common manifestations that link them together, whereas
      a highly variable clinical course exists that spans from mild and subtle findings
      to aggressive, life-threatening multisystem disease. The physician needs to
      carefully characterize each patient to understand the specific manifestations and
      level of disease activity to decide appropriate treatment. This is particularly
      important in treating a patient with scleroderma because there is no treatment
      that has been proven to modify the overall disease course, although therapy that
      targets specific organ involvement early before irreversible damage occurs
      improves both quality of life and survival. This review describes our approach as
      defined by evidence, expert opinion, and our experience treating patients.
      Scleroderma is a multisystem disease with variable expression; thus, any
      treatment plan must be holistic, yet at the same time focus on the dominant organ
      disease. The goal of therapy is to improve quality of life by minimizing specific
      organ involvement and subsequent life-threatening disease. At the same time the
      many factors that alter daily function need to be addressed, including nutrition,
      pain, deconditioning, musculoskeletal disuse, comorbid conditions, and the
      emotional aspects of the disease, such as fear, depression, and the social
      withdrawal caused by disfigurement.

PMID- 23541015
TI  - Association between ipilimumab and celiac disease.
AB  - A 62-year-old man with chemotherapy-naive, castration-resistant metastatic
      prostate cancer presented with refractory diarrhea despite prolonged high-dose
      corticosteroid treatment after receiving 3 doses of ipilimumab as part of a phase
      3 clinical trial. The investigative work-up and response to a gluten-free diet
      essentially confirm celiac disease. Although ipilimumab-induced enterocolitis is
      a well-reported complication, there have been no reported cases of celiac disease
      with ipilimumab therapy, to our knowledge. We suspect that ipilimumab may have
      amplified the symptomatic presentation of previously unrecognized celiac disease
      or perhaps even triggered the disease itself. With ipilimumab being used more
      commonly in the treatment of melanoma and prostate cancer, we believe that
      physicians should be aware of this potential adverse outcome when evaluating a
      patient who experiences persistent diarrhea during or after ipilimumab treatment.

PMID- 23541016
TI  - Osteonecrosis of the jaw after osteoporosis therapy with denosumab following long
      term bisphosphonate therapy.
AB  - Osteonecrosis of the jaw (ONJ) is a common and potentially severe complication of
      antiresorptive therapy for bone metastases. However, its occurrence in patients
      treated for osteoporosis is rare. Although poor oral hygiene and invasive dental
      procedures have been identified as potential triggers, little is known about the
      role of other systemic risk factors. We describe a patient who developed ONJ
      after her first treatment with denosumab, a monoclonal antibody against receptor
      activator of NF-kappaB ligand. This patient had several comorbidities that
      prompted us to assess the German ONJ registry for the incidence of comorbidities
      in patients with ONJ. In summary, almost half of the patients (35 of 86 [41%])
      had 1 or more risk factors thought to increase the risk of ONJ. In conclusion,
      comorbidities or comedications may increase the susceptibility of developing ONJ
      during osteoporosis therapy.

PMID- 23541017
TI  - Comments and questions regarding the safety of citalopram.

PMID- 23541018
TI  - In reply.

PMID- 23541019
TI  - Prognostic risk score for pleocytosis with a negative gram stain: valid but of
      limited utility in bacterial meningitis patients.

PMID- 23541020
TI  - In reply.

PMID- 23541021
TI  - Silent brain abscess in patients with infective endocarditis.

PMID- 23541022
TI  - Horace Magoun--neuroanatomist and neurophysiologist.

PMID- 23541024
TI  - Exaggerated insect bite reaction related to chronic leukemia.

PMID- 23541025
TI  - Tumour imaging by Positron Emission Tomography using fluorinase generated 5
      [18F]fluoro-5-deoxyribose as a novel tracer.
AB  - INTRODUCTION: 5-[(18)F]Fluoro-5-deoxyribose ([(18)F]FDR) 3 was prepared as a
      novel monosaccharide radiotracer in a two-step synthesis using the fluorinase, a
      C-F bond forming enzyme, and a nucleoside hydrolase. The resulting [(18)F]FDR 3
      was then explored as a radiotracer for imaging tumours (A431 human epithelial
      carcinoma) by positron emission tomography in a mice model. METHODS: 5
      [(18)F]Fluoro-5-deoxyribose ([(18)F]FDR) 3, was prepared by incubating S-adenosyl
      L-methionine (SAM) and [(18)F]fluoride with the fluorinase enzyme, and then
      incubating the product of this reaction, [(18)F]-5'-fluoro-5'-deoxadenosine
      ([(18)F]FDA) 2, with an adenosine hydrolase to generate [(18)F]FDR 3. The enzymes
      were freeze-dried and were used on demand by dissolution in buffer solution. The
      resulting [(18)F]FDR 3 was then administered to four mice that had tumours
      induced from the A431 human epithelial carcinoma cell line. RESULTS: The tumour
      (A431 human epithelial carcinoma) bearing mice were successfully imaged with
      [(18)F]FDR 3. The radiotracer displayed good tumour imaging resolution. A direct
      comparison of the uptake and efflux of [(18)F]FDR 3 with 2-[(18)F]fluoro-2
      deoxyglucose ([(18)F]FDG) was made, revealing comparative tumour uptake and
      imaging potential over the first 10-20min. The study revealed however that
      [(18)F]FDR 3 does not accumulate in the tumour as efficiently as [(18)F]FDG over
      longer time periods. CONCLUSIONS: [(18)F]FDR 3 can be rapidly synthesised in a
      two enzyme protocol and used to image tumours in small animal models.

PMID- 23541026
TI  - Preclinical evaluation of NETA-based bifunctional ligand for radioimmunotherapy
      applications using 212Bi and 213Bi: radiolabeling, serum stability, and
      biodistribution and tumor uptake studies.
AB  - INTRODUCTION: Despite the great potential of targeted alpha-radioimmunotherapy
      (RIT) as demonstrated by pre-clinical and clinical trials, limited progress has
      been made on the improvement of chelation chemistry for (212)Bi and (213)Bi. A
      new bifunctional ligand 3p-C-NETA was evaluated for targeted alpha RIT using
      (212)Bi and (213)Bi. METHODS: Radiolabeling of 3p-C-NETA with (205/6)Bi, a
      surrogate of (212)Bi and (213)Bi, was evaluated at pH5.5 and room temperature. In
      vitro stability of the (205/6)Bi-3p-C-NETA-trastuzumab conjugate was evaluated
      using human serum (pH7, 37  degrees C). Immunoreactivity and specific activity of
      the (205/6)Bi-3p-C-NETA-trastuzumab conjugate were measured. An in vivo
      biodistribution study was performed to evaluate the in vivo stability and tumor
      targeting properties of the (205/6)Bi-3p-C-NETA-trastuzumab conjugate in athymic
      mice bearing subcutaneous LS174T tumor xenografts. RESULT: The 3p-C-NETA
      trastuzumab conjugate was extremely rapid in complexing with (205/6)Bi, and the
      corresponding (205/6)Bi-3p-C-NETA-trastuzumab was stable in human serum.
      (205/6)Bi-3p-C-NETA-trastuzumab was prepared with a high specific activity and
      retained immunoreactivity. (205/6)Bi-3p-C-NETA-trastuzumab conjugate displayed
      excellent in vivo stability and targeting as evidenced by low normal organ and
      high tumor uptake. CONCLUSION: The results of the in vitro and in vivo studies
      indicate that 3p-C-NETA is a promising chelator for RIT applications using
      (212)Bi and (213)Bi. Further detailed in vivo evaluations of 3p-C-NETA for
      targeted alpha RIT are warranted.

PMID- 23541027
TI  - In situ identification and N2 and C fixation rates of uncultivated cyanobacteria
      populations.
AB  - Nitrogen (N2) fixation is a globally important process often mediated by
      diazotrophic cyanobacteria in the open ocean. In 2010, seawater was collected
      near Cape Verde to identify and measure N2 and carbon (C) fixation by unicellular
      diazotrophic cyanobacteria. The nifH gene abundance (104-106 nifH L-1) and nifH
      gene transcript abundance (102-104 cDNA nifHL-1) for two unicellular groups, UCYN
      A and UCYN-B, were detected. UCYN-A was also identified and quantified (104
      105cells L-1) by new probes (UCYN-A732 and UCYN-A159) using Catalyzed Reporter
      Deposition-Fluorescence In Situ Hybridization (CARD-FISH) assays. The UCYN-A were
      observed as free cells or attached to a larger unidentified eukaryotic cell. A
      Halogen In Situ Hybridization-Secondary Ion Mass Spectrometry (HISH-SIMS) assay
      using the UCYN-A732 probe was applied on samples previously incubated with 13C
      bicarbonate and 15N2. Free UCYN-A cells were enriched in both 13C and 15N and
      estimated C and N2 fixation rates for UCYN-A were lower compared to co-occurring
      unicellular cyanobacteria cells similar in size (3.1-5.6 MUm) and pigmentation to
      diazotroph Crocosphaera watsonii. Here, we identify and quantify two common co
      occurring unicellular groups and measure their cellular activities by nanoSIMS.

PMID- 23541028
TI  - Formation of [Ni(III)(kappa(1)-S2CH)(P(o-C6H3-3-SiMe3-2-S)3)]- via CS2 insertion
      into nickel(III) hydride containing [Ni(III)(H)(P(o-C6H3-3-SiMe3-2-S)3)]-.
AB  - Insertion of CS2 into the thermally unstable nickel(III) hydride [PPN][Ni(H)(P(o
      C6H3-3-SiMe3-2-S)3)] (1), freshly prepared from the reaction of
      [PPN][Ni(OC6H5)P(C6H3-3-SiMe3-2-S)3] and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane
      (HBpin; pin = OCMe2CMe2O) in tetrahydrofuran at -80  degrees C via a metathesis
      reaction, readily affords [PPN][Ni(III)(kappa(1)-S2CH)(P(o-C6H3-3-SiMe3-2-S)3)]
      (2) featuring a kappa(1)-S2CH moiety.

PMID- 23541029
TI  - Lipopolysaccharide structure of Helicobacter pylori serogroup O:3.
AB  - In this study, we describe a re-investigation of the lipopolysaccharide structure
      of Helicobacter pylori serogroup O:3. Application of NMR and MS approaches to the
      analysis of oligosaccharides obtained through degradation of LPS from H. pylori
      serogroup O:3 by various methods confirmed that its general architecture was
      identical to that of LPS from H. pylori strains 26695 and SS1 and followed a
      sequential linear assembly of the alpha-1,6-glucan, dd-heptan, and O-chain
      components. Additionally, MALDI-MS analysis demonstrated that a significant
      proportion of H. pylori serogroup O:3 LPS was terminated with alpha-1,6-glucan
      and was not further substituted by dd-heptan and the O-chain polysaccharide.

PMID- 23541031
TI  - Spin system trajectory analysis under optimal control pulses.
AB  - Several methods are proposed for the analysis, visualization and interpretation
      of high-dimensional spin system trajectories produced by quantum mechanical
      simulations. It is noted that expectation values of specific observables in large
      spin systems often feature fast, complicated and hard-to-interpret time dynamics
      and suggested that populations of carefully selected subspaces of states are much
      easier to analyze and interpret. As an illustration of the utility of the
      proposed methods, it is demonstrated that the apparent "noisy" appearance of many
      optimal control pulses in NMR and EPR spectroscopy is an illusion - the
      underlying spin dynamics is shown to be smooth, orderly and very tightly
      controlled. 

PMID- 23541030
TI  - Histone h3 glutathionylation in proliferating mammalian cells destabilizes
      nucleosomal structure.
AB  - AIMS: Here we report that chromatin, the complex and dynamic eukaryotic DNA
      packaging structure, is able to sense cellular redox changes. Histone H3, the
      only nucleosomal protein that possesses cysteine(s), can be modified by
      glutathione (GSH). RESULTS: Using Biotin labeled glutathione ethyl ester (BioGEE)
      treatment of nucleosomes in vitro, we show that GSH, the most abundant
      antioxidant in mammals, binds to histone H3. BioGEE treatment of NIH3T3 cells
      indicates that glutathionylation of H3 is maximal in fast proliferating cells,
      correlating well with enhanced levels of H3 glutathionylation in different tumor
      cell lines. Furthermore, glutathionylation of H3 in vivo decreases in livers from
      aged SAMP8 and C57BL/6J mice. We demonstrate biochemically and by mass
      spectrometry that histone variants H3.2/H3.3 are glutathionylated on their
      cysteine residue 110. Furthermore, circular dichroism, thermal denaturation of
      reconstituted nucleosomes, and molecular modeling indicate that glutathionylation
      of histone H3 produces structural changes affecting nucleosomal stability.
      INNOVATION: We characterize the implications of histone H3 glutathionylation in
      cell physiology and the modulation of core histone proteins structure affected by
      this modification. CONCLUSION: Histone H3 senses cellular redox changes through
      glutathionylation of Cys, which increases during cell proliferation and decreases
      during aging. Glutathionylation of histone H3 affects nucleosome stability
      structure leading to a more open chromatin structure.

PMID- 23541032
TI  - Plant growth-promoting rhizobacteria strain Bacillus amyloliquefaciens NJN-6
      enriched bio-organic fertilizer suppressed Fusarium wilt and promoted the growth
      of banana plants.
AB  - Bacillus amyloliquefaciens strain NJN-6 is an important plant growth-promoting
      rhizobacteria (PGPR) which can produce secondary metabolites antagonistic to
      several soil-borne pathogens. In this study, the ability of a bio-organic
      fertilizer (BIO) containing NJN-6 strain to promote the growth and suppress
      Fusarium wilt of banana plants was evaluated in a pot experiment. The results
      showed that the application of BIO significantly decreased the incidence of
      Fusarium wilt and promoted the growth of banana plants compared to that for the
      organic fertilizer (OF). To determine the beneficial mechanism of the strain, the
      colonization of NJN-6 strain on banana roots was evaluated using scanning
      electron microscopy (SEM). The plant growth-promoting hormones indole-3-acetic
      acid (IAA) and gibberellin A3 (GA3), along with antifungal lipopeptides iturin A,
      were detected when the NJN-6 strain was incubated in both Landy medium with
      additional l-tryptophan and in root exudates of banana plants. In addition, some
      antifungal volatile organic compounds and iturin A were also detected in BIO. In
      summary, strain NJN-6 could colonize the roots of banana plants after the
      application of BIO and produced active compounds which were beneficial for the
      growth of banana plants. 

PMID- 23541033
TI  - Schizophrenia susceptibility and age of diagnosis--a frailty approach.
AB  - BACKGROUND: Using a frailty model approach, we aim to evaluate the effect of
      early-life risk factors on susceptibility and age at diagnosis of schizophrenia.
      We assume paternal age and familial schizophrenia influence the susceptibility,
      while these and several early risk factors influence the age of diagnosis.
      METHOD: Schizophrenia incidence data were derived from the population-based
      Swedish Patient Registry; including individuals aged 18 to 45 years, diagnosed
      between 1974 and 2008. Data were analyzed by a frailty model, a random effects
      model in survival analysis, using a compound Poisson model. RESULTS: 15,340
      incident schizophrenia cases were included. For individuals without familial
      schizophrenia, a protective effect was seen across most ages of diagnosis for
      females, low paternal age, born in rural areas, and being born in later cohorts.
      For individuals with familial schizophrenia, a protective effect is found for
      females diagnosed between ages 18 and 30 years, corresponding values were 18-25
      years for low paternal age. Being born in rural areas and in the last birth
      cohort was protective for all. The estimated proportion of susceptible was 5% for
      those without familial schizophrenia and 18% for individuals with familial
      schizophrenia. There was no statistically significant effect of paternal age on
      the proportion of susceptible. DISCUSSION: To our knowledge, this is the first
      regression modeling of time to schizophrenia diagnosis allowing for a non
      susceptible fraction of the population, including age dependent modeling of
      covariate effects and an interaction. Applying frailty model to schizophrenia
      provide etiological clues, elucidating patterns of susceptibility and age-at
      diagnosis for which early-life factors are of importance.

PMID- 23541036
TI  - Reprogramming by cell fusion: boosted by Tets.
AB  - Pluripotent cells, when fused with somatic cells, have the dominant ability to
      reprogram the somatic genome. Work by Piccolo et al. (2013) shows that the Tet1
      and Tet2 hydroxylases are important for DNA methylation reprogramming of
      pluripotency genes and parental imprints.

PMID- 23541037
TI  - Histone Crosstalk: H2Bub and H3K4 Methylation.
AB  - Two new studies in this issue of Molecular Cell (Kim et al., 2013 and Wu et al.,
      2013) provide new insights and reignite debate over how histone H2B
      ubiquitination promotes methylation of histone H3 lysine 4.

PMID- 23541038
TI  - Methylating the DNA of the most repressed: special access required.
AB  - A new study (Zemach et al., 2013) suggests that the chromatin remodeling ATPase
      DDM1 is specifically required for cytosine methylation at linker histone H1
      associated heterochromatin, facilitating access by three cytosine
      methyltransferases, including a previously uncharacterized CHH methylase, CMT2.

PMID- 23541039
TI  - Optimal hemoglobin A1C Cutoff Value for Diagnosing type 2 diabetes mellitus in
      Korean adults.
AB  - Commonly used tests for the diagnosis of diabetes include measurements of fasting
      plasma glucose levels and the oral glucose tolerance test (OGTT). Recently, a
      hemoglobin A1C (A1C) level of 6.5% has been included as a criterion for diabetes
      diagnosis by the American Diabetes Association. We aimed to determine appropriate
      A1C cutoff values for identifying patients with diabetes or prediabetes,
      including impaired glucose tolerance and impaired fasting glucose among Korean
      adults and to determine whether these cutoffs vary according to age. We recruited
      4616 adults without a history of diabetes from 10 university hospitals. A 75-g
      OGTT and A1C sampling were performed in all examinees. Pointwise area under the
      receiver operating characteristic curve was used to evaluate the diagnostic
      accuracy of the A1C cutoff. An A1C threshold of 6.1% proved to be the optimal
      limit for diagnosing diabetes, with 63.8% sensitivity and 88.1% specificity. The
      cutoff value increased with age (5.9% in 18-39 years, 6.2% in 40-64 years, and
      6.4% in older than 65 years) and were similar for men and women. An A1C cutoff of
      5.7% had reasonable sensitivity (48.6%) and specificity (65.7%) for the
      identification of prediabetes. Further prospective studies should be carried out
      to determine whether the application of age-specific diagnostic criteria is
      appropriate.

PMID- 23541040
TI  - Gestational diabetes mellitus--challenges in research and management.

PMID- 23541042
TI  - Ocular graft-versus-host disease: a review.
AB  - Graft-versus-host disease (GVHD) is a common cause of morbidity and mortality
      after allogeneic hematopoietic stem cell transplantation. Systemic findings
      involving the skin, gastrointestinal tract, and liver often overshadow the other
      manifestations of GVHD. Ocular surface disease remains the most common cause of
      long-term morbidity in GVHD. Herein, the etiology, pathophysiology, clinical
      manifestations, and treatment of acute and chronic systemic GVHD are reviewed,
      with a focus on ocular GVHD.

PMID- 23541041
TI  - Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis.
AB  - Serpiginous choroiditis (SC) is a posterior uveitis displaying a geographic
      pattern of choroiditis, extending from the juxtapapillary choroid and
      intermittently spreading centrifugally. The choroiditis involves the overlying
      retinal pigment epithelium, and the outer retina. This intraocular inflammation
      typically involves both eyes in otherwise healthy, middle-aged individuals with
      no familial or ethnic predilection. Pathogenesis is unclear; based on limited
      histopathologic studies, however, favorable response to immunosuppressive agents,
      and the absence of association with systemic or local infectious or noninfectious
      diseases, an organ-specific autoimmune inflammation seems likely to be the
      underlying process. Patients, particularly from tuberculosis-endemic regions, may
      present with fundus changes simulating SC, but show evidence of active
      tuberculosis and/or the presence of mycobacterial DNA in the aqueous humor. This
      has been referred to as serpiginous-like choroiditis, but we prefer the
      description multifocal serpiginoid choroiditis (MSC). We present the
      distinguishing features of SC and infectious multifocal serpiginoid choroiditis
      simulating SC. The distinction is crucial to avoid unnecessarily treating SC with
      antimicrobial agents. Advances in diagnostic and imaging modalities can help
      differentiate SC from MSC. Novel local and systemic treatment approaches improve
      the outcome and preserve vision in SC.

PMID- 23541044
TI  - Experimental testing of quantum mechanical predictions of mutagenicity:
      aminopyrazoles.
AB  - A computational method for predicting the likelihood of aromatic amines being
      active in the Ames test for mutagenicity was trialed on a set of aminopyrazoles.
      A virtual array of compounds was generated from the available sets of hydrazines
      and alpha-cyanoaldehydes (or ketones) and quantum mechanical calculations used to
      compute a probability of being active in the Ames test. The compounds selected
      for synthesis and testing were not based on the predictions and so spanned the
      range of predicted probabilities. The subsequently generated results of the Ames
      test were in good correspondence with the predictions and confirm this approach
      as a useful means of predicting likely mutagenic risk.

PMID- 23541043
TI  - Multisite intracerebral microdialysis to study the mechanism of L-DOPA induced
      dopamine and serotonin release in the parkinsonian brain.
AB  - L-DOPA is currently one of the best medications for Parkinson's disease. It was
      assumed for several years that its benefits and side effects were related to the
      enhancement of dopamine release in the dopamine-depleted striatum. The use of
      intracerebral microdialysis combined with a pharmacological approach has led to
      the discovery that serotonergic neurons are responsible for dopamine release
      induced by L-DOPA. The subsequent use of multisite microdialysis has further
      revealed that L-DOPA-stimulated dopamine release is widespread and related to the
      serotonergic innervation. The present Review emphasizes the functional impact of
      extrastriatal release of dopamine induced by L-DOPA in both the therapeutic and
      side effects of L-DOPA. 

PMID- 23541047
TI  - Dental anomalies in a Portuguese population.
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence and pattern of
      agenesis, supernumerary teeth, impacted teeth and transpositions, as well as the
      relation between them, in a Portuguese sample. MATERIAL AND METHODS: The study
      sample consisted of 2888 patients, observed between 2005 and 2009 at the
      Dentistry Clinic of the Instituto Superior de Ciencias da Saude-Norte (ISCSN,
      Portugal). The study included evaluation of the following parameters: agenesis of
      all teeth, supernumerary teeth, impacted permanent teeth and tooth transposition.
      The age range varied from 7 to 21 years. In order to study the absence of the
      third molar, subjects aged below 14 years were excluded. Statistical analysis was
      performed using SPSS((r)). RESULTS: Excluding third molars, the prevalence of
      tooth agenesis, supernumerary teeth, impacted teeth and transpositions was 6.1%,
      0.8%, 1.8% and 0.2%, respectively, for this Portuguese population. There was a
      significantly higher prevalence of supernumerary teeth in males than in females
      (P < 0.05). The mesiodens was the most frequent supernumerary tooth, the upper
      canine was the most frequent impacted tooth, and the upper canine and upper
      lateral were the two most frequently transposed teeth. There was a significantly
      higher prevalence of missing third molars in the impacted canine group than in
      the non-impacted canine group (P < 0.05). CONCLUSIONS: Agenesis is the most
      frequent dental anomaly. There are no differences between genders, except for
      supernumerary teeth, which are found more frequently in men. A relation between
      third molar agenesis and impacted canines was found.

PMID- 23541045
TI  - Theoretical impact of insecticide-impregnated school uniforms on dengue incidence
      in Thai children.
AB  - BACKGROUND: Children carry the main burden of morbidity and mortality caused by
      dengue. Children spend a considerable amount of their day at school; hence
      strategies that reduce human-mosquito contact to protect against the day-biting
      habits of Aedes mosquitoes at schools, such as insecticide-impregnated uniforms,
      could be an effective prevention strategy. METHODOLOGY: We used mathematical
      models to calculate the risk of dengue infection based on force of infection
      taking into account the estimated proportion of mosquito bites that occur in
      school and the proportion of school time that children wear the impregnated
      uniforms. PRINCIPAL FINDINGS: The use of insecticide-impregnated uniforms has
      efficacy varying from around 6% in the most pessimistic estimations, to 55% in
      the most optimistic scenarios simulated. CONCLUSIONS: Reducing contact between
      mosquito bites and human hosts via insecticide-treated uniforms during school
      time is theoretically effective in reducing dengue incidence and may be a
      valuable additional tool for dengue control in school-aged children. The efficacy
      of this strategy, however, is dependent on the compliance of the target
      population in terms of proper and consistent wearing of uniforms and, perhaps
      more importantly, the proportion of bites inflicted by the Aedes population
      during school time.

PMID- 23541048
TI  - [Teaching of laparoscopic surgery colorectal. The Lapco model].

PMID- 23541049
TI  - Sphingosine 1-phosphate receptor agonists: a patent review (2010-2012).
AB  - INTRODUCTION: The sphingosine-1-phosphate (S1P)-driven signaling regulates
      fundamental biological functions, including cell proliferation, angiogenesis,
      endothelial cell chemotaxis, immune cell trafficking and mitogenesis. A large
      body of research has been focusing on the development of immunosuppressive S1P1
      receptor (S1P1-R) agonist molecules. The S1P(1,3-5)-R pan-agonist fingolimod
      (FTY720) has been approved by the FDA for the treatment of relapsing-remitting
      multiple sclerosis. However, FTY720 is now contraindicated in patients with
      compromised cardiac function. Although the main adverse effect bradycardia has
      been linked to the S1P3-R activation, cardiovascular liabilities persist with
      more selective S1P1-R agonists that have entered clinical trials. In contrast to
      the S1P1-R, the therapeutic application of the S1P(2-5)-Rs remains poorly
      explored. AREAS COVERED: This review provides the patent literature from 2010 to
      date on S1P-R agonist molecules and their relevant biological properties. EXPERT
      OPINION: Limited progress has been made on agonists at S1P(4,5)-R subtypes, with
      some families of S1P5-R agonists showing promising results in animal models of
      age-related cognitive disorders. A discrete number of reviewed molecules are S1P1
      R agonists with a promising clinical outlook in transplantation, inflammation,
      cancer and autoimmune settings. Further preclinical and clinical studies will
      determine whether the new developed S1P1-R agonists do indeed improve the safety
      profile of FTY720.

PMID- 23541050
TI  - Health in Europe--successes, failures, and new challenges.

PMID- 23541051
TI  - Health in Europe--policies for progress.

PMID- 23541052
TI  - A healthy perspective: the post-2015 development agenda.

PMID- 23541053
TI  - The unequal health of Europeans: successes and failures  of policies.
AB  - Europe, with its 53 countries and divided history, is a remarkable but
      inadequately exploited natural laboratory for studies of the eff ects of health
      policy. In this paper, the fi rst in a Series about health in Europe, we review
      developments in population health in Europe, with a focus on trends in mortality,
      and draw attention to the main successes and failures of health policy in the
      past four decades. In western Europe, life expectancy has improved almost
      continuously, but progress has been erratic in eastern Europe, and, as a result,
      disparities in male life expectancy between the two areas are greater now than
      they were four decades ago. The falls in mortality noted in western Europe are
      associated with many different causes of death and show the combined eff ects of
      economic growth, improved health care, and successful health policies (eg,
      tobacco control, road traffic safety). Less favourable mortality trends in
      eastern Europe show economic and health-care problems and a failure to implement
      effective health policies. The political history of Europe has left deep
      divisions in the health of the population. Important health challenges remain in
      both western and eastern Europe and signify unresolved issues in health policy
      (eg, alcohol, food) and rising health inequalities within countries.

PMID- 23541054
TI  - Health law and policy in the European Union.
AB  - From its origins as six western European countries coming together to reduce
      trade barriers, the European Union (EU) has expanded, both geographically and in
      the scope of its actions, to become an important supranational body whose
      policies affect almost all aspects of the lives of its citizens. This influence
      extends to health and health services. The EU's formal responsibilities in health
      and health services are limited in scope, but, it has substantial indirect
      influence on them. In this paper, we describe the institutions of the EU, its
      legislative process, and the nature of European law as it affects free movement
      of the goods, people, and services that affect health or are necessary to deliver
      health care. We show how the influence of the EU goes far beyond the activities
      that are most visible to health professionals, such as research funding and
      public health programmes, and involves an extensive body of legislation that
      affects almost every aspect of health and health care.

PMID- 23541055
TI  - Health and health systems in the Commonwealth of  Independent States.
AB  - The countries of the Commonwealth of Independent States differ substantially in
      their post-Soviet economic development but face many of the same challenges to
      health and health systems. Life expectancies dropped steeply in the 1990s, and
      several countries have yet to recover the levels noted before the dissolution of
      the Soviet Union. Cardiovascular disease is a much bigger killer in the
      Commonwealth of Independent States than in western Europe because of hazardous
      alcohol consumption and high smoking rates in men, the breakdown of social safety
      nets, rising social inequality, and inadequate health services. These former
      Soviet countries have embarked on reforms to their health systems, often aiming
      to strengthen primary care, scale back hospital capacities, reform mechanisms for
      paying providers and pooling funds, and address the overall shortage of public
      funding for health. However, major challenges remain, such as frequent private
      out-of-pocket payments for health care and underdeveloped systems for improvement
      of quality of care.

PMID- 23541056
TI  - Health services for children in western Europe.
AB  - Western European health systems are not keeping pace with changes in child health
      needs. Non-communicable diseases are increasingly common causes of childhood
      illness and death. Countries are responding to changing needs by adapting child
      health services in different ways and useful insights can be gained through
      comparison, especially because some have better outcomes, or have made more
      progress, than others. Although overall child health has improved throughout
      Europe, wide inequities remain. Health services and social and cultural
      determinants contribute to differences in health outcomes. Improvement of child
      health and reduction of suffering are achievable goals. Development of systems
      more responsive to evolving child health needs is likely to necessitate
      reconfiguring of health services as part of a whole-systems approach to
      improvement of health. Chronic care services and first-contact care systems are
      important aspects. The Swedish and Dutch experiences of development of integrated
      systems emphasise the importance of supportive policies backed by adequate
      funding. France, the UK, Italy, and Germany offer further insights into chronic
      care services in different health systems. First-contact care models and the
      outcomes they deliver are highly variable. Comparisons between systems are
      challenging. Important issues emerging include the organisation of first-contact
      models, professional training, arrangements for provision of out-of-hours
      services, and task-sharing between doctors and nurses. Flexible first-contact
      models in which child health professionals work closely together could offer a
      way to balance the need to provide expertise with ready access. Strategies to
      improve child health and health services in Europe necessitate a whole-systems
      approach in three interdependent systems-practice (chronic care models, first
      contact care, competency standards for child health professionals), plans (child
      health indicator sets, reliable systems for capture and analysis of data, scale
      up of child health research, anticipation of future child health needs), and
      policy (translation of high-level goals into actionable policies, open and
      transparent accountability structures, political commitment to delivery of
      improvements in child health and equity throughout Europe).

PMID- 23541057
TI  - Ageing in the European Union.
AB  - The ageing of European populations presents health, long-term care, and welfare
      systems with new challenges. Although reports of ageing as a fundamental threat
      to the welfare state seem exaggerated, societies have to embrace various policy
      options to improve the robustness of health, long-term care, and welfare systems
      in Europe and to help people to stay healthy and active in old age. These policy
      options include prevention and health promotion, better self-care, increased
      coordination of care, improved management of hospital admissions and discharges,
      improved systems of long-term care, and new work and pension arrangements. Ageing
      of the health workforce is another challenge, and policies will need to be
      pursued that meet the particular needs of older workers (ie, those aged 50 years
      or older) while recruiting young practitioners.

PMID- 23541058
TI  - Migration and health in an increasingly diverse Europe.
AB  - The share of migrants in European populations is substantial and growing, despite
      a slowdown in immigration after the global economic crisis. This paper describes
      key aspects of migration and health in Europe, including the scale of
      international migration, available data for migrant health, barriers to accessing
      health services, ways of improving health service provision to migrants, and
      migrant health policies that have been adopted across Europe. Improvement of
      migrant health and provision of access for migrants to appropriate health
      services is not without challenges, but knowledge about what steps need to be
      taken to achieve these aims is increasing.

PMID- 23541059
TI  - Financial crisis, austerity, and health in Europe.
AB  - The financial crisis in Europe has posed major threats and opportunities to
      health. We trace the origins of the economic crisis in Europe and the responses
      of governments, examine the effect on health systems, and review the effects of
      previous economic downturns on health to predict the likely consequences for the
      present. We then compare our predictions with available evidence for the effects
      of the crisis on health. Whereas immediate rises in suicides and falls in road
      traffic deaths were anticipated, other consequences, such as HIV outbreaks, were
      not, and are better understood as products of state retrenchment. Greece, Spain,
      and Portugal adopted strict fiscal austerity; their economies continue to recede
      and strain on their health-care systems is growing. Suicides and outbreaks of
      infectious diseases are becoming more common in these countries, and budget cuts
      have restricted access to health care. By contrast, Iceland rejected austerity
      through a popular vote, and the financial crisis seems to have had few or no
      discernible effects on health. Although there are many potentially confounding
      differences between countries, our analysis suggests that, although recessions
      pose risks to health, the interaction of fiscal austerity with economic shocks
      and weak social protection is what ultimately seems to escalate health and social
      crises in Europe. Policy decisions about how to respond to economic crises have
      pronounced and unintended effects on public health, yet public health voices have
      remained largely silent during the economic crisis.

PMID- 23541060
TI  - Health in Europe--a view from across the Atlantic.

PMID- 23541061
TI  - Novel collagen/gelatin scaffold with sustained release of basic fibroblast growth
      factor: clinical trial for chronic skin ulcers.
AB  - Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing
      and are a costly problem in healthcare. We have developed a novel artificial
      dermis, collagen/gelatin sponge (CGS), which is capable of sustained release of
      basic fibroblast growth factor (bFGF) for more than 10 days. The objective of
      this study was to investigate the safety and efficacy of CGS impregnated with
      bFGF in the treatment of chronic skin ulcers. Patients with chronic skin ulcers
      that had not healed in at least 4 weeks were treated with CGS impregnated with
      bFGF at 7 or 14 MUg/cm(2) after debridement, and the wound bed improvement was
      assessed 14 days after application. Wound bed improvement was defined as a
      granulated and epithelialized area on day 14 with a proportion to the baseline
      wound area after debridement of 50% or higher. The wound area, the wound area on
      day 14, and the granulation area on day 14 were independently measured by blinded
      reviewers in a central review using digital images of wounds taken with a
      calibrator. Patients were followed up until 28 days after application to observe
      the adverse reactions related to the application of CGS. From May 2010 to June
      2011, 17 patients were enrolled and, in 16 patients, the wound bed improved.
      Among the randomized patients in step 2, no significant difference was seen
      between the low-dose group and the high-dose group. No serious adverse reactions
      were observed. Adverse reactions with a clear causal relationship to the study
      treatment were mild and patients quickly recovered from them. This study is the
      first-in-man clinical trial of CGS and showed the safety and efficacy of CGS
      impregnated with bFGF in the treatment of chronic skin ulcers. This combination
      therapy could be a promising therapy for chronic skin ulcers.

PMID- 23541062
TI  - 1,3-Dipolar cycloadditions of ruthenium(II) azido complexes with alkynes and
      nitriles.
AB  - The diazido complex [Na][Ru(N3)2{kappa(3)(N,N,N)-Tpms}(PPh3)] (1) (Tpms =
      tris(pyrazolyl)methanesulfonate) has been synthesized, and its reactivity toward
      dipolarophiles has been investigated. Thus, the reaction of 1 with alkynes leads
      to complexes with one or two triazolate ligands depending on the alkyne and the
      reaction conditions. Complex 1 also reacts with nitriles. Thus, the reaction with
      RCN (R = Me, Ph) leads to the substitution products [Ru(N3)(NCR){kappa(3)(N,N,N)
      Tpms}(PPh3)]. However, when fumaronitrile is used, a complex containing a new
      kappa(2)(N(1),N(3))-5-(1,2,3-triazol-4-yl)-1,2,3,4-tetrazolate ligand is obtained
      as the result of two consecutive cycloaddition reactions. The mechanism for this
      unusual reaction has been unambiguously established through the isolation of the
      intermediate complex resulting from a first cycloaddition between a coordinated
      azide and the C?C double bond.

PMID- 23541063
TI  - SEMICYUC 2012. Recommendations for intensive care management of acute
      pancreatitis.
AB  - OBJECTIVE: Significant changes in the management of acute pancreatitis have taken
      place since the 2004 Pamplona Consensus Conference. The objective of this
      conference has been the revision and updating of the Conference recommendations,
      in order to unify the integral management of potentially severe acute
      pancreatitis in an ICU. PARTICIPANTS: Spanish and international intensive
      medicine physicians, radiologists, surgeons, gastroenterologists, emergency care
      physicians and other physicians involved in the treatment of acute pancreatitis.
      LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION: The GRADE method has been used
      for drawing them up. DRAWING UP THE RECOMMENDATIONS: The selection of the
      committee members was performed by means of a public announcement. The
      bibliography has been revised from 2004 to the present day and 16 blocks of
      questions on acute pancreatitis in a ICU have been drawn up. Firstly, all the
      questions according to groups have been drawn up in order to prepare one
      document. This document has been debated and agreed upon by computer at the
      SEMICYUC Congress and lastly at the Consensus Conference which was held with the
      sole objective of drawing up these recommendations. CONCLUSIONS: Eighty two
      recommendations for acute pancreatitis management in an ICU have been presented.
      Of these 84 recommendations, we would emphasize the new determinants-based
      classification of acute pancreatitis severity, new surgical techniques and
      nutritional recommendations. Note. This summary only lists the 84 recommendations
      of the 16 questions blocks except blocks greater relevance and impact of its
      novelty or because they modify the current management.

PMID- 23541065
TI  - Predictors of acute postsurgical pain and anxiety following primary total hip and
      knee arthroplasty.
AB  - This study aims to examine the joint role of demographic, clinical, and
      psychological variables as predictors of acute postsurgical pain and anxiety in
      patients undergoing total knee arthroplasty and total hip arthroplasty. A
      consecutive sample of 124 patients was assessed 24 hours before (T1) and 48 hours
      after (T2) surgery. Demographic, clinical, and psychological factors were
      assessed at T1 and several postsurgical pain issues, anxiety, and analgesic
      consumption were evaluated at T2. Hierarchical linear regression analyses were
      performed to identify predictors of acute pain and anxiety following surgery. In
      the final multivariate model, presurgical optimism emerged as the main
      significant predictor of postsurgical pain intensity. Presurgical optimism also
      had a significant role in the prediction of postsurgical anxiety, together with
      presurgical anxiety level and emotional representation of the condition leading
      to surgery (osteoarthritis). A significant positive correlation between
      postsurgical anxiety and acute pain was also confirmed. The present study
      enhances our understanding of predictors of acute pain and anxiety following
      total knee arthroplasty and total hip arthroplasty by showing the relevance of
      psychological factors, over and above other potential clinical predictors. These
      findings could be used to develop targeted interventions aimed at acute
      postsurgical pain and anxiety management following major joint arthroplasties.
      PERSPECTIVE: This article reveals the significant influence of psychological
      factors on the prediction of acute pain and anxiety 48 hours after primary total
      hip and knee arthroplasty. These results could prove useful for the design of
      interventions aimed at postsurgical pain and anxiety management.

PMID- 23541064
TI  - Trientine reduces BACE1 activity and mitigates amyloidosis via the AGE/RAGE/NF
      kappaB pathway in a transgenic mouse model of Alzheimer's disease.
AB  - AIMS: There is mounting evidence that the transition metal copper may play an
      important role in the pathophysiology of Alzheimer's disease (AD). Triethylene
      tetramine dihydrochloride (trientine), a CuII-selective chelator, is a commonly
      used treatment for Wilson's disease to decrease accumulated copper, and thereby
      decreases oxidative stress. In the present study, we evaluated the effects of a 3
      month treatment course of trientine (Trien) on amyloidosis in 7-month-old beta
      amyloid (Abeta) precursor protein and presenilin-1 (APP/PS1) double transgenic
      (Tg) AD model mice. RESULTS: We observed that Trien reduced the level of advanced
      glycation end products (AGEs), and decreased Abeta deposition and synapse loss in
      brain of APP/PS1 mice. Importantly, we found that Trien blocked the receptor for
      AGEs (RAGE), downregulated beta-site APP cleaving enzyme 1 (BACE1), inhibited
      amyloidogenic APP cleavage, and subsequently reduced Abeta levels. In vitro, in
      SH-SY5Y cells overexpressing Swedish mutant APP, Trien-mediated downregulation of
      BACE1 occurred via inhibition of the NF-kappaB signaling pathway. INNOVATION: In
      this study, we demonstrated for the first time that Trien inhibited amyloidogenic
      pathway including targeting the downregulation of RAGE and NF-kappaB. CONCLUSION:
      Trien might mitigate amyloidosis in AD by inhibiting the RAGE/NF-kappaB/BACE1
      pathway. Our study demonstrates that Trien may be a viable therapeutic strategy
      for the intervention and treatment of AD and other AD-like pathologies.

PMID- 23541067
TI  - Clinicians' attitudes and beliefs about opioids survey (CAOS): instrument
      development and results of a national physician survey.
AB  - Beliefs surrounding the use of opioids for chronic noncancer pain have vacillated
      over time. Concerns regarding long-term efficacy and adverse effects of opioids,
      along with increases in opioid prescribing, have contributed to many political,
      regulatory, and clinical responses. The present study was designed to (1) develop
      a reliable and valid measure (Clinicians' Attitudes about Opioids Scale [CAOS])
      to assess current and evolving beliefs regarding opioids and opioid use in
      patients with chronic pain; and (2) survey these beliefs in a nationally
      representative sample of providers from multiple medical specialties throughout
      the United States. We developed the questionnaire in 3 phases: (1) focus groups
      and content development; (2) pilot testing and subsequent revisions; and (3)
      formal survey (N = 1,535) and assessment of stability (N = 251). The resulting 38
      item measure assessed 5 domains: (1) Impediments and Concerns; (2) Perceived
      Effectiveness; (3) Schedule II versus III Opioids; (4) Medical Education; and (5)
      Tamper Resistant Formulations. No significant differences were identified among
      geographical regions; however, several differences were observed among medical
      specialties. Orthopedists were most troubled by impediments/concerns from long
      term opioid use and had the least confidence in opioid efficacy, whereas Pain
      Medicine specialists and Physical Medicine and Rehabilitation specialists were
      the most confident in efficacy. PERSPECTIVE: This article presents the
      psychometric properties of a new measure of clinicians' beliefs surrounding
      opioid use for chronic pain. Using this measure, beliefs and behaviors of
      physicians across medical specialties and geographic regions using a nationally
      representative sample are presented, updating findings from a similar survey
      conducted 20 years ago.

PMID- 23541066
TI  - Conditioned pain modulation in children and adolescents: effects of sex and age.
AB  - Conditioned pain modulation (CPM) refers to the diminution of perceived pain
      intensity for a test stimulus following application of a conditioning stimulus to
      a remote area of the body, and is thought to reflect the descending inhibition of
      nociceptive signals. Studying CPM in children may inform interventions to enhance
      central pain inhibition within a developmental framework. We assessed CPM in 133
      healthy children (mean age = 13 years; 52.6% girls) and tested the effects of sex
      and age. Participants were exposed to 4 trials of a pressure test stimulus
      before, during, and after the application of a cold water conditioning stimulus.
      CPM was documented by a reduction in pressure pain ratings during cold water
      administration. Older children (12-17 years) exhibited greater CPM than younger
      children (8-11 years). No sex differences in CPM were found. Lower heart rate
      variability at baseline and after pain induction was associated with less CPM,
      controlling for child age. The findings of greater CPM in the older age cohort
      suggest a developmental improvement in central pain inhibitory mechanisms. The
      results highlight the need to examine developmental and contributory factors in
      central pain inhibitory mechanisms in children to guide effective, age
      appropriate pain interventions. PERSPECTIVE: In this healthy sample, younger
      children exhibited less CPM than did older adolescents, suggesting a
      developmental improvement in CPM. Cardiac vagal tone was associated with CPM
      across age. The current findings may inform the development of targeted,
      developmentally appropriate pain interventions for children.

PMID- 23541068
TI  - Muscle hyperalgesia correlates with motor function in complex regional pain
      syndrome type 1.
AB  - At present it is unclear if disturbed sensory processing plays a role in the
      development of the commonly observed motor impairments in patients with complex
      regional pain syndrome (CRPS). This study aims to investigate the relation
      between sensory and motor functioning in CRPS patients with and without dystonia.
      Patients with CRPS of the arm and controls underwent comprehensive quantitative
      sensory testing and kinematic analysis of repetitive finger movements. Both CRPS
      groups showed thermal hypoesthesia to cold and warm stimuli and hyperalgesia to
      cold stimuli. A decreased pressure pain threshold reflecting muscle hyperalgesia
      emerged as the most prominent sensory abnormality in both patient groups and was
      most pronounced in CRPS patients with dystonia. Moreover, the decreased pressure
      pain threshold was the only nociceptive parameter that related to measures of
      motor function in both patients and controls. CRPS patients with dystonia had an
      increased 2-point discrimination as compared to controls and CRPS patients
      without dystonia. This finding was also reported in other types of dystonia and
      has been associated to cortical reorganization in response to impaired motor
      function. We hypothesize that increased sensitivity of the circuitry mediating
      muscle nociception may play a crucial role in impaired motor control in CRPS.
      PERSPECTIVE: This is the first study linking a sensory dysfunction, ie, muscle
      hyperalgesia, to motor impairment in CRPS. Circuitries mediating muscle
      nociception may therefore play an important role in impaired motor control in
      CRPS.

PMID- 23541069
TI  - Changes in pain coping, catastrophizing, and coping efficacy after cognitive
      behavioral therapy in children and adolescents with juvenile fibromyalgia.
AB  - A recent randomized multisite clinical trial found that cognitive-behavioral
      therapy (CBT) was significantly more effective than fibromyalgia education (FE)
      in reducing functional disability in adolescents with juvenile fibromyalgia
      (JFM). The primary objective of this study was to examine the psychological
      processes of CBT effectiveness by evaluating changes in pain coping,
      catastrophizing, and coping efficacy and to test these changes as mediators of
      continued improvements in functional disability and depressive symptoms at 6
      month follow-up. One hundred adolescents (11-18 years old) with JFM completed the
      clinical trial. Coping, catastrophizing, and coping efficacy (Pain Coping
      Questionnaire) and the outcomes of functional disability (Functional Disability
      Inventory) and depressive symptoms (Children's Depression Inventory) were
      measured at baseline, posttreatment, and 6-month follow-up. Participants in both
      conditions showed significant improvement in coping, catastrophizing, and
      efficacy by the end of the study, but significantly greater improvements were
      found immediately following treatment for those who received CBT. Treatment gains
      were maintained at follow-up. Baseline to posttreatment changes in coping,
      catastrophizing, and efficacy were not found to mediate improvements in
      functional disability or depressive symptoms from posttreatment to follow-up.
      Future directions for understanding mechanisms of CBT effectiveness in
      adolescents with chronic pain are discussed. PERSPECTIVE: CBT led to significant
      improvements in pain coping, catastrophizing, and efficacy that were sustained
      over time in adolescents with juvenile fibromyalgia. Clinicians treating
      adolescents with JFM should focus on teaching a variety of adaptive coping
      strategies to help patients simultaneously regain functioning and improve mood.

PMID- 23541070
TI  - The role of the ubiquitin proteasome system in lymphoma.
AB  - The ubiquitin-proteasome system (UPS) maintains the integrity of cellular
      processes by controlling protein degradation pathways. The role of the UPS in
      proliferation, cell cycle, differentiation, DNA repair, protein folding, and
      apoptosis is well documented, and a wide range of protein activities in these
      signaling pathways can be manipulated by UPS inhibitors, which include many anti
      cancer agents. Naturally occurring and synthetic drugs designed to target the UPS
      are currently used for hematological cancers, including lymphoma. These drugs
      largely interfere with the E1 and E2 regions of the 26S proteasome, blocking
      proteasomal activity and promoting apoptosis by enhancing activities of the
      extrinsic (death receptors, Trail, Fas) and intrinsic (caspases, Bax, Bcl2, p53,
      nuclear factor-kappa B, p27) cell death programs. This review focuses on recent
      clinical developments concerning UPS inhibitors, signaling pathways that are
      affected by down-regulation of UPS activities, and apoptotic mechanisms promoted
      by drugs in this class that are used to treat lymphoma.

PMID- 23541071
TI  - Current status and future directions in induction chemotherapy for head and neck
      cancer.
AB  - As a component of multimodal therapy in locally advanced head and neck cancer,
      induction chemotherapy represents a strategy to reduce tumor burden and target
      distant metastases prior to definitive treatment. Although the addition of
      taxanes to the cisplatin and 5-fluorouracil induction regimen (TPF) has greatly
      benefitted outcomes in comparison with PF alone, recent phase III trials have not
      shown a survival advantage for TPF induction followed by chemoradiotherapy vs.
      chemoradiotherapy alone. While these trials may have been underpowered to
      demonstrate a survival benefit, additional phase III trials are ongoing, with
      highly anticipated results. "Next-generation" sequential regimens that include
      targeted agents such as cetuximab are emerging as an approach to increase
      activity while decreasing toxicity. In addition, patient selection based on
      individual disease characteristics may identify ideal candidates for induction
      therapy. These developments may result in personalized therapeutic regimens that
      improve clinical outcomes. 

PMID- 23541072
TI  - Self assembly of nanoislands on YSZ-(001) surface: a mechanistic approach toward
      a robust process.
AB  - We experimentally investigate the mechanism of formation of self-assembled arrays
      of nanoislands surrounding dopant sources on the (001) surface of yttria
      stabilized zirconia. Initially, we used lithographically defined thin-film
      patches of gadolinia-doped ceria (GDC) as dopant sources. During annealing at
      approximately one-half the melting temperature of zirconia, surface diffusion of
      dopants leads to the breakup of the surface around the source, creating arrays of
      epitaxial nanoislands with a characteristic size (~100 nm) and alignment along
      elastically compliant directions, <110>. The breakup relieves elastic strain
      energy at the expense of increasing surface energy. On the basis of understanding
      the mechanism of island formation, we introduce a simple and versatile powder
      based doping process for spontaneous surface patterning. The new process bypasses
      lithography and conventional vapor-source doping, opening the door to spontaneous
      surface patterning of functional ceramics and other refractory materials. In
      addition to using GDC solid-solution powders, we demonstrate the effectiveness of
      the process in another system based on Eu2O3.

PMID- 23541073
TI  - Ocular integrity following manganese labeling of the visual system for MRI.
AB  - Injection of manganese into the eye will enhance the contrast of visual system
      neuronal pathways imaged by MRI (MEMRI). The present study was undertaken to
      determine the effect of a range of MnCl2 doses upon the integrity of various
      ocular structures. Anesthetized mice received ocular anterior chamber injections
      of 50-500 nmol of MnCl2. One week later, the eyes were fixed, embedded in
      paraffin, sectioned, and stained with hematoxylin and eosin. Additional animals
      received 50 nmol of MnCl2 injected into the anterior chamber and were later
      imaged using T1-weighted 7T MRI. Following 500 and 300nmol MnCl2, the corneal
      stroma and endothelium were degenerated, the anterior chamber contained a dense
      fibrin matrix with extensive inflammatory cell infiltration, a plaque often
      formed on the anterior lens, and significant retinal degeneration was observed.
      Following 100nmol MnCl2, retinal preservation of ocular structures was
      significantly better than at higher doses. In addition, there was no difference
      from vehicle control retina in cell counts within the ganglion cell layer, or in
      the width of the inner nuclear layer or outer nuclear layer. Also, there was no
      difference in the thickness of the inner plexiform layer. However, there was
      thinning of the peripheral outer plexiform layer, as well as in the outer segment
      layer. Visual system elements labeled in MRI of mice that received 100nmol MnCl2
      included the retina, optic nerve, lateral geniculate nucleus, and superior
      colliculus. The preservation of ganglion cell layer cell counts and inner
      plexiform layer thickness following 100nmol MnCl2 suggests there was negligible
      injury to RGCs following this dose. These results support using 100nmol MnCl2 in
      mouse eyes for in vivo assessment of the integrity of RGC projections to target
      neurons in the brain.

PMID- 23541074
TI  - A role for 16S rRNA dimethyltransferase (ksgA) in intrinsic clarithromycin
      resistance in Mycobacterium tuberculosis.
AB  - The emergence of extensively drug-resistant tuberculosis (XDR-TB) makes the
      control of tuberculosis (TB) difficult. As a result, there is an urgent need to
      develop new anti-TB drugs. Alternatively, drugs that have already been used in
      humans as anti-infectives and later found to have antitubercular activity might
      be useful as anti-TB drugs, particularly against drug-resistant TB.
      Clarithromycin (CLR), a 14-membered macrolide and protein synthesis inhibitor,
      has potent activity against most mycobacterial infections, except Mycobacterium
      tuberculosis. Mycobacterium tuberculosis is naturally resistant to CLR [minimum
      inhibitory concentration (MIC) of 8-16 MUg/mL] owing to the presence of inducible
      erm methylase (ErmMT). With a view to gaining further insight into the mechanisms
      of innate CLR resistance in M. tuberculosis, CLR-susceptible M. tuberculosis
      H37Rv mutants were generated by transposon mutagenesis. One mutant, designated as
      Tn-196, was further investigated and it was found that ksgA (Rv1010) was
      inactivated by the transposon. The ksgA gene encodes a 16S rRNA adenine
      dimethyltransferase that methylates A1518 and A1519 (Escherichia coli numbering)
      of 16S rRNA and plays an important role in ribosome biogenesis. Complementation
      of the Tn-196 mutant with a wild-type ksgA gene restored the resistant phenotype
      (MIC of 8-16 MUg/mL), corroborating the association of ksgA with intrinsic CLR
      resistance in M. tuberculosis.

PMID- 23541075
TI  - Penetrating atherosclerotic ulcer of the aorta: a continuing debate.
AB  - Aortic penetrating atherosclerotic ulcer (PAU) is a relatively common incidental
      finding on thoracic computed tomography (CT) examinations. This is likely to
      relate to the steady increase in the number of CT examinations performed and also
      due, in part, to the increasing age of the general population. There is as yet no
      consensus on the management of incidental PAUs in asymptomatic patients. This
      article aims to review the literature and discuss the natural history, prognosis,
      and management of incidental PAU. 

PMID- 23541076
TI  - Optimized GC-MS method to simultaneously quantify acetylated aldose, ketose, and
      alditol for plant tissues based on derivatization in a methyl sulfoxide/1
      methylimidazole system.
AB  - The isomers of monosaccharide always produce multiple chromatographic peaks as
      volatile derivatives during gas chromatography, which may result in the
      overlapping of different sugar peaks. Whereas reduction and oximation of sugar
      carbonyl groups for GC analysis do eliminate many isomer derivatives, the
      approaches create new problems. One ketose can yield two peaks by oximation, and
      different aldoses and ketoses can yield the same alditol upon reduction, leading
      to the inability to detect some important monosaccharides. This paper reports an
      optimal method that yields a single peak per sugar by acetylation directly. By
      using a methyl sulfoxide (Me2SO)/1-methylimidazole (1-MeIm) system, the
      carbohydrates in acetic anhydride (Ac2O) esterification reactions were
      solubilized, and the oxidation that normally occurs was inhibited. The results
      demonstrate that acetylated derivatives of 23 saccharides had unique peaks, which
      indicates aldose, ketose, and alditol can be determined simultaneously by GC-MS. 

PMID- 23541082
TI  - Molecular characterization of three mitoviruses co-infecting a hypovirulent
      isolate of Sclerotinia sclerotiorum fungus.
AB  - Three double-stranded RNAs (dsRNAs) of 2438 nts (A), 2588 nts (B), and 2744 nts
      (C), from a single isolate of Sclerotinia sclerotiorum were sequenced. All three
      sequences showed similarity to known mitoviruses, consisting of a single open
      reading frame (ORF) with the characteristic conserved motifs of RNA-dependent RNA
      polymerase (RdRp). Mitochondrial malformations and reduced virulence and growth
      were associated with the presence of the dsRNAs. The terminal sequences of the
      (+) strand of the three dsRNAs could be folded into stem-loop structures and the
      inverted terminal complimentary sequences of dsRNA-A potentially form a panhandle
      structure. Sequence A showed 91.6% aa similarity to the previously described
      Sclerotinia sclerotiorum mitovirus 2 and was tentatively assigned the acronym
      SsMV2/NZ1. Sequences B and C showed only 16.4% similarity to each other and 15
      48% aa similarity to the previously described mitoviruses and consequently appear
      to be new mitoviruses.

PMID- 23541081
TI  - Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and
      requires PML SUMOylation but not other known cellular PML regulators, CK2 and
      E6AP, to mediate PML degradation.
AB  - All gammaherpsviruses encode at least one gene related to the cellular
      formylglycinamide ribonucleotide amidotransferase (FGARAT) enzyme but their
      biological roles are relatively unknown. The murine gammaherpesvirus 68 (MHV68)
      vFGARAT, ORF75c, mediates a proteasome-dependent degradation of the antiviral
      promyelocytic leukemia (PML) protein by an unknown mechanism, which is addressed
      in this study. We found that ORF75c interacts weakly with PML and SUMO-modified
      forms of PML are important for its degradation by ORF75c. ORF75c-mediated PML
      degradation was not dependent on two known cellular regulators of PML stability,
      Casein kinase II (CK2) and human papilloma virus E6-associated protein (E6AP).
      Finally, ORF75c had self-ubiquitination activity in vitro and its expression
      increased levels of ubiquitinated PML in transfected cells. Taken together, the
      evidence accumulated in this study provides new insights into the function of a
      vFGARAT and is consistent with a model in which ORF75c could mediate direct
      ubiquitination of PML resulting in its degradation by the proteasome.

PMID- 23541083
TI  - Influence of overlapping genes on the evolution of human hepatitis B virus.
AB  - The aim of this work was to analyse the influence of overlapping genes on the
      evolution of hepatitis B virus (HBV). A differential evolutionary behaviour among
      genetic regions and clinical status was found. Dissimilar levels of conservation
      of the different protein regions could derive from alternative mechanisms to
      maintain functionality. We propose that, in overlapping regions, selective
      constraints on one of the genes could drive the substitution process. This would
      allow protein conservation in one gene by synonymous substitutions while
      mechanisms of tolerance to the change operate in the overlapping gene (e.g. usage
      of amino acids with high-degeneracy codons, differential codon usage and
      replacement by physicochemically similar amino acids). In addition, differential
      selection pressure according to the HBeAg status was found in all genes,
      suggesting that the immune response could be one of the factors that would
      constrain viral replication by interacting with different HBV proteins during the
      HBeAg(-) stage.

PMID- 23541084
TI  - Involvement of histone methyltransferase GLP in HIV-1 latency through catalysis
      of H3K9 dimethylation.
AB  - Understanding the mechanism of HIV-1 latency is crucial to eradication of the
      viral reservoir in HIV-1-infected individuals. However, the role of histone
      methyltransferase (HMT) G9a-like protein (GLP) in HIV-1 latency is still unclear.
      In the present work, we established four clonal cell lines containing HIV-1
      vector. We found that the integration sites of most clonal cell lines favored
      active gene regions. However, we also observed hypomethylation of CpG of HIV
      5'LTR in all four clonal cell lines. Additionally, 5'-deoxy-5'
      methylthioadenosine (MTA), a broad-spectrum histone methyltransferase inhibitor,
      was used to examine the role of histone methylation in HIV-1 latency. MTA was
      found to decrease the level of H3K9 dimethylation, causing reactivation of latent
      HIV-1 in C11 cells. GLP knockdown by small interfering RNA clearly induced HIV-1
      LTR expression. Results suggest that GLP may play a significant role in the
      maintenance of HIV-1 latency by catalyzing dimethylation of H3K9.

PMID- 23541085
TI  - Methylation status of CEBPA gene promoter in chronic myeloid leukemia.
AB  - CCAAT/enhancer binding protein alpha is one of the crucial transcription factors
      for myeloid cell development that has been found to be involved in hematopoietic
      differentiation and leukemiogenesis. Recently, epigenetic regulation of CEBPA
      expression through DNA methylation has been demonstrated in leukemia. The aim of
      this study was to investigate the methylation status of CEBPA gene in chronic
      myeloid leukemia (CML) patients. The methylation status of CEBPA promoter was
      studied in 100 patients with CML and 98 normal healthy individuals from
      Hyderabad, India, using methylation-specific polymerase chain reaction. The
      aberrant methylation of CEBPA gene promoter was found in 32 of the 100 CML cases.
      A highly significant association was found between the frequency of CEBPA gene
      promoter hypermethylation and the CML stages (P = 0.017), but association with
      respect to age and gender of the patient was not found. The results suggest that
      aberrant methylation in the CpG island of the promoter region of this gene might
      be a common event in CML, and systemic expression studies will be needed to
      unfold the role of CEBPA promoter methylation in the development, progression,
      and prognosis of CML.

PMID- 23541086
TI  - T-cells from HLA-B*57:01+ human subjects are activated with abacavir through two
      independent pathways and induce cell death by multiple mechanisms.
AB  - Susceptibility to abacavir hypersensitivity has been attributed to possession of
      the specific human leukocyte antigen allele HLA-B*57:01. HLA-B*57:01-restricted
      activation of CD8+ T-cells provides a link between the genetic association and
      the iatrogenic disease. The objectives of this study were to characterize the
      functionality of drug-responsive CD8+ T-cell clones generated from HLA-B*57:01+
      drug-naive subjects and to explore the relationship between abacavir accumulation
      in antigen presenting cells and the T-cell response. Seventy-four CD8+ clones
      expressing different Vbeta receptors were shown to proliferate and kill target
      cells via different mechanisms when exposed to abacavir. Certain clones were
      activated with abacavir in the absence of antigen presenting cells. Analysis of
      the remaining clones revealed two pathways of drug-dependent T-cell activation.
      Overnight incubation of antigen presenting cells with abacavir, followed by
      repeated washing to remove soluble drug, activated approximately 50% of the
      clones, and the response was blocked by glutaraldehyde fixation. In contrast, a 1
      h antigen presenting cell pulse did not activate any of the clones. Accumulation
      of abacavir in antigen presenting cells was rapid (less than 1 h), and the
      intracellular concentrations were maintained for 16 h. However, intracellular
      abacavir was not detectable by mass spectrometry after pulsing. These data
      suggest that T-cells can be activated by abacavir through a direct interaction
      with surface and intracellular major histocompatibility complex (MHC) molecules.
      With the former, abacavir seemingly participates in the MHC T-cell receptor
      binding interaction. In contrast, the latter pathway likely involves MHC binding
      peptides displayed as a consequence of abacavir exposure, but not abacavir
      itself.

PMID- 23541087
TI  - A drought-sensitive barley variety displays oxidative stress and strongly
      increased contents in low-molecular weight antioxidant compounds during water
      deficit compared to a tolerant variety.
AB  - Barley displays a great genetic diversity, constituting a valuable source to
      delineate the responses of contrasted genotypes to environmental constraints.
      Here, we investigated the level of oxidative stress and the participation of
      antioxidant systems in two barley genotypes: Express, a variety known to be
      sensitive to drought, and Saida, an Algerian landrace selected for its tolerance
      to water deficit. Soil-grown 15-day-old plants were subjected to water deficit
      for 8 days and then rewatered. We observed that upon water stress Express
      exhibits compared to Saida accelerated wilting and a higher level of oxidative
      stress evaluated by HPLC measurements of lipid peroxidation and by imaging
      techniques. In parallel, Express plants also display lower levels of catalase and
      superoxide dismutase activity. No great difference was observed regarding
      peroxiredoxins and methionine sulfoxide reductases, enzymes detoxifying peroxides
      and repairing oxidized proteins, respectively. In contrast, upon water stress and
      recovery, much higher contents and oxidation ratios of glutathione and ascorbate
      were measured in Express compared to Saida. Express also shows during water
      deficit greater increases in the pools of lipophilic antioxidants like xantophyll
      carotenoids and alpha-tocopherol. Altogether, these data show that the
      differential behavior of the two genotypes involves distinct responses regarding
      antioxidant mechanisms. Indeed, the drought sensitivity of Express compared with
      Saida is associated with oxidative damage and a lower enzymatic ROS-scavenging
      capacity, but in parallel with a much stronger enhancement of most mechanisms
      involving low-molecular weight antioxidant compounds.

PMID- 23541088
TI  - Autosomal dominant cases of chronic mucocutaneous candidiasis segregates with
      mutations of signal transducer and activator of transcription 1, but not of Toll
      like receptor 3.
AB  - We report a family with autosomal dominant chronic mucocutaneous candidiasis as
      well as recurrent viral infections that segregate with a novel signal transducer
      and activator of transcription 1 (STAT1) mutation. Prophylactic treatment with
      fluconazole and immunoglobulin replacement has been initiated, with good clinical
      response. 

PMID- 23541089
TI  - Remarkable stability of clinical grade reagents for gene-engineered T-lymphocyte
      production.

PMID- 23541090
TI  - An analysis of the implementation of PEPFAR's anti-prostitution pledge and its
      implications for successful HIV prevention among organizations working with sex
      workers.
AB  - INTRODUCTION: Since 2003, US government funding to address the HIV and AIDS
      pandemic has been subject to an anti-prostitution clause. Simultaneously, the
      efficacy of some HIV prevention efforts for sex work in areas receiving US
      government funding has diminished. This article seeks to explain why. METHODS:
      This analysis utilizes a case story approach to build a narrative of defining
      features of organizations in receipt of funding from the President's Emergency
      Plan for AIDS Relief (PEPFAR) and other US funding sources. For this analysis,
      multiple cases were compiled within a single narrative. This helps show
      restrictions imposed by the anti-prostitution clause, any lack of clarity of
      guidelines for implementation and ways some agencies, decision-making personnel,
      and staff on the ground contend with these restrictions. RESULTS: Responses to
      PEPFAR's anti-prostitution clause vary widely and have varied over time.
      Organizational responses have included ending services for sex workers, gradual
      phase-out of services, cessation of seeking US government HIV funds and
      increasing isolation of sex workers. Guidance issued in 2010 did not clarify what
      was permitted. Implementation and enforcement has been dependent in part on the
      interpretations of this policy by individuals, including US government
      representatives and organizational staff. CONCLUSIONS: Different interpretations
      of the anti-prostitution clause have led to variations in programming, affecting
      the effectiveness of work with sex workers. The case story approach proved ideal
      for working with information like this that is highly sensitive and vulnerable to
      breach of anonymity because the method limits the potential to betray confidences
      and sources, and limits the potential to jeopardize funding and thereby
      jeopardize programming. This method enabled us to use specific examples without
      jeopardizing the organizations and individuals involved while demonstrating
      unintended consequences of PEPFAR's anti-prostitution pledge in its provision of
      services to sex workers and clients.

PMID- 23541091
TI  - Surveillance of patients post-endovascular abdominal aortic aneurysm repair
      (EVAR). A web-based survey of practice in the UK.
AB  - AIM: To evaluate the current practice of endovascular abdominal aortic aneurysm
      repair (EVAR) surveillance amongst British Society of Interventional Radiologists
      (BSIR) members. MATERIALS AND METHODS: A web-based survey (Surveymonkey.com) of
      BSIR members was performed from June 2011 to September 2011. Questions included
      who was responsible for organizing follow-up, techniques used in follow-up, and
      timing of follow-up imaging. RESULTS: The majority (46%) of follow-up is
      organized by radiologists. In the first year, 74% of imaging interactions
      involves the use of computed tomography (CT), with 40% of respondents using
      multiple phases. After the first year, ultrasound is utilized more frequently,
      usually with plain films. Most patients receive imaging at 1, 6, and 12 months,
      and thereafter most respondents plan on indefinite yearly follow-up. CONCLUSION:
      EVAR follow-up protocols in the past have been empirical rather than evidence
      based. The present survey shows the current range of protocols used in the UK.
      Despite the frequent use of CT in the first year post-EVAR, there does appear to
      be a trend towards using ultrasound after the first year of follow-up.

PMID- 23541092
TI  - Bilateral calcific myonecrosis associated with epilepsy.

PMID- 23541093
TI  - Static and dynamic evaluation of pelvic floor disorders with an open low-field
      tilting magnet.
AB  - AIM: To assess the feasibility of magnetic resonance defaecography (MRD) in
      pelvic floor disorders using an open tilting magnet with a 0.25 T static field
      and to compare the results obtained from the same patient both in supine and
      orthostatic positions. MATERIALS AND METHODS: From May 2010 to November 2011, 49
      symptomatic female subjects (mean age 43.5 years) were enrolled. All the patients
      underwent MRD in the supine and orthostatic positions using three-dimensional
      (3D) hybrid contrast-enhanced (HYCE) sequences and dynamic gradient echo (GE) T1
      weighted sequences. All the patients underwent conventional defaecography (CD) to
      correlate both results. Two radiologists evaluated the examinations; inter and
      intra-observer concordance was measured. The results obtained in the two
      positions were compared between them and with CD. RESULTS: The comparison between
      CD and MRD found statistically significant differences in the evaluation of
      anterior and posterior rectocoele during defaecation in both positions and of
      rectal prolapse under the pubo-coccygeal line (PCL) during evacuation, only in
      the supine position (versus MRD orthostatic: rectal prolapse p < 0.0001; anterior
      rectocoele p < 0.001; posterior rectocoele p = 0.008; versus CD: rectal prolapse
      p < 0.0001; anterior rectocoele p < 0.001; posterior rectocoele p = 0.01). The
      value of intra-observer intra-class correlation coefficient (ICC) ranged from
      good to excellent; the interobserver ICC from moderate to excellent. CONCLUSION:
      MRD is feasible with an open low-field tilting magnet, and it is more accurate in
      the orthostatic position than in the supine position to evaluate pelvic floor
      disorders.

PMID- 23541094
TI  - Presence of left atrial diverticula, accessory appendages, and normal variant
      pulmonary venous anatomy diagnosed using MDCT and adverse outcomes following
      radiofrequency catheter ablation therapy in patients with drug-refractory atrial
      fibrillation: an exploratory study.
AB  - AIM: To determine the frequency of normal variation left atrial anatomy (NVLAA)
      (diverticula, accessory appendages) and normal variation pulmonary venous anatomy
      (NVPVA) in patients with atrial fibrillation (AF), and to determine whether the
      presence of these entities is associated with an increased recurrence of atrial
      arrhythmias following radiofrequency catheter ablation (RFCA). MATERIALS AND
      METHODS: All cardiac MDCT images performed prior to RFCA between November 2009
      and May 2011 in patients with drug-refractory AF were retrospectively evaluated.
      The presence, type, and location of NVLAA and NVPVA, and outcome of RFCA were
      recorded. Success was defined as restoration of sinus rhythm. RESULTS: Forty-six
      consecutive patients with a mean age of 59.8 (+/-9.7) years (76.1% male)
      underwent cardiac MDCT for anatomical planning prior to RFCA procedures. Fourteen
      (30.4%) patients had NVLAA, 35% of patients had NVPVA. Thirty (65%) patients had
      successful RFCA: 57% of these had a NVLAA, 67% had NVPVA. Sixteen (35%) patients
      had unsuccessful RFCA: 63% of these had a NVLAA, 56% had NVPVA. There was no
      significant association between the presence of NVLAA (p = 0.699), NVPVA (p =
      0.197), or "NVLAA in the presence of normal pulmonary venous anatomy" (p = 0.589)
      and the outcome of RFCA. CONCLUSION: The presence of NVLAA and NVPVA appears
      unrelated to adverse outcome in patients undergoing RFCA for the treatment of
      drug-refractory AF.

PMID- 23541095
TI  - A completed audit cycle of the lateral scan projection radiograph in CT pulmonary
      angiography (CTPA); the impact on scan length and radiation dose.
AB  - AIM: To investigate the effect of incorporating a lateral scan projection
      radiograph (topogram) in addition to the standard frontal topogram on excess scan
      length in computed tomography pulmonary angiography (CTPA) and to quantify the
      impact on effective dose. MATERIALS AND METHODS: Fifty consecutive patients
      referred for exclusion of pulmonary embolism who had undergone a CTPA examination
      with conventional frontal topogram to plan scan length (protocol A) were compared
      with 50 consecutive patients who had undergone a CTPA study with frontal and
      additional lateral topogram for planning (protocol B) in a retrospective audit.
      Optimal scan length was defined from lung apex to lung base. Mean excess scan
      length beyond these landmarks was determined. The mean organ doses to the
      thyroid, liver, and stomach, as well as mean effective dose, were estimated using
      standard conversion factors. RESULTS: The mean excess scan length was
      significantly lower in protocol B compared to the protocol A cohort (19.5 +/-
      17.4 mm [mean +/- standard deviation] versus 39.1 +/- 20.4 mm, p < 0.0001). The
      mean excess scan length below the lung bases was significantly lower in the
      protocol B cohort compared to the protocol A group (7.5 +/- 12.7 mm versus 23 +/-
      16.6 mm, p < 0.0001), as were the mean organ doses to the stomach (4.24 +/- 0.81
      mGy versus 5.22 +/- 1.06 mGy, p < 0.0001) and liver (5.60 +/- 0.64 mGy versus
      6.38 +/- 0.81 mGy, p < 0.0001). A non-significant reduction in over-scanning
      above the apices in protocol B was observed compared with protocol A (12 +/- 8.8
      mm versus 16.2 +/- 13.6 mm, p = 0.07), which equated to lower mean thyroid organ
      dose in (3.28 +/- 1.76 mGy versus 4.11 +/- 3.11 mGy, p = 0.104). CONCLUSION: The
      present audit indicates that incorporation of a lateral topogram into the CTPA
      protocol, together with radiographer education, reduces excess scan length, which
      significantly reduces the dose to the liver and stomach, and potentially lowers
      the dose to the thyroid. This simple dose-saving technique can be applied to all
      CT investigations of the chest on all CT systems with immediate effect.

PMID- 23541096
TI  - Commentary on atrial masses on multidetector computed tomography.

PMID- 23541097
TI  - Susceptibility weighted imaging in the evaluation of movement disorders.
AB  - Movement disorders are neurodegenerative disorders associated with abnormalities
      of brain iron deposition. In this presentation, we aim to describe the role of
      susceptibility weighted imaging (SWI) in the imaging of patients with movement
      disorders and differentiate between the various disorders. SWI is a high
      resolution, fully velocity-encoded gradient-echo magnetic resonance imaging (MRI)
      sequence that consists of using both magnitude and phase information. We describe
      briefly the physics behind this sequence and the post-processing techniques used.
      The anatomy of the midbrain and basal ganglia in normal subjects on SWI is
      covered. A number of neurodegenerative disorders are associated with abnormal
      iron deposition, which can be detected due to the susceptibility effects.

PMID- 23541098
TI  - A prospective study of injury affecting competitive collegiate swimmers.
AB  - The purposes of this study were to determine the incidence and distribution of
      injuries affecting collegiate competitive swimmers and to test possible injury
      risk factors. A prospective cohort design was used to follow 34 swimmers (16 M,
      18 F) from an NCAA Division I Midwest University over one academic year. Exposure
      based injury rates were determined for both practice and competition. Risk of
      injury was assessed relative to gender, years swimming, and history of injury.
      Twenty of 34 swimmers sustained 31 injuries with overall injury rates of 5.55
      injuries per 1000 athlete exposures and 3.04 injuries per 1000 hours exposure.
      Practice injury rates for female swimmers were higher than for women's practice
      injury rates in other NCAA sports. The most common injury locations were the
      shoulder, back, and knee. Risk factors that remained significant in the
      multivariate analysis were history of injury to the same anatomical location and
      history of injury at other anatomical sites.

PMID- 23541099
TI  - Physiological and neuromuscular indices associated with sprint running
      performance.
AB  - The purpose of the study was to analyze the relationships among physiological and
      neuromuscular indices with the 200- and 400-m sprint running performance.
      Fourteen male sprinters performed the following tests: determination of 200-
      (P200) and 400-m (P400) running performance; determination of VO2max and the
      velocity associated at VO2max; squat jump (SJ) and countermovement jump (CMJ);
      and maximal accumulated oxygen deficit (MAOD). Significant correlations were
      observed between SJ (r = -0.53), CMJ (r = -0.69), and MAOD (r = -0.65) with P200.
      Countermovement jump (CMJ) and MAOD explained 70% of the P200. The MAOD was the
      only variable to correlate significantly with P400 (r = -0.56); VO2max and CMJ
      were also selected in the regression together and explained 79% of P400. The
      indicators of muscular power and anaerobic capacity are capable of explaining
      P200. In the 400 m, the performance was determined by indices of anaerobic
      capacity, in conjunction with the athletes' aerobic and muscular power.

PMID- 23541100
TI  - Validity of COSMED's quark CPET mixing chamber system in evaluating energy
      metabolism during aerobic exercise in healthy male adults.
AB  - This study validated the accuracy of COSMED's Quark cardiopulmonary exercise
      testing (CPET) metabolic mixing chamber system in measuring metabolic factors
      during maximal, graded exercise testing. Subjects included 32 physically active
      men between the ages of 18 and 34 years. During the first test session, subjects
      were measured for maximal oxygen consumption twice (15 min separation) with the
      CPET and Douglas bag systems (random order). During the second test session,
      subjects exercised through four stages of the Bruce treadmill protocol with
      measurement by the CPET and Douglas bag systems (random order) during steady
      state at the end of each 3-minute stage. Statistical analysis using a 2 (systems)
      x 5 (time) repeated measures ANOVA showed that the pattern of change in VO2,
      VCO2, VE, FeO2, FeCO2, and RER did not differ significantly between CPET and
      Douglas bag systems. This validation study indicates that the CPET mixing chamber
      system provides valid metabolic measurements that compare closely with the
      Douglas bag system during aerobic exercise.

PMID- 23541101
TI  - The age-related performance decline in ultraendurance mountain biking.
AB  - The age-related changes in ultraendurance performance have been previously
      examined for running and triathlon but not mountain biking. The aims of this
      study were (i) to describe the performance trends and (ii) to analyze the age
      related performance decline in ultraendurance mountain biking in a 120-km
      ultraendurance mountain bike race the "Swiss Bike Masters" from 1995 to 2009 in
      9,325 male athletes. The mean (+/-SD) race time decreased from 590 +/- 80 min to
      529 +/- 88 min for overall finishers and from 415 +/- 8 min to 359 +/- 16 min for
      the top 10 finishers, respectively. The mean (+/-SD) age of all finishers
      significantly (P < 0.001) increased from 31.6 +/- 6.5 years to 37.9 +/- 8.9
      years, while the age of the top 10 remained stable at 30.0 +/- 1.6 years. The
      race time of mountain bikers aged between 25 and 34 years was significantly (P <
      0.01) faster compared with the race time of older age groups. The age-related
      decline in performance in endurance mountain bikers in the "Swiss Bike Masters"
      appears to start earlier compared with other ultraendurance sports.

PMID- 23541102
TI  - Injury type and incidence among elite level curlers during world championship
      competition.
AB  - Our objective was to investigate the incidence of musculoskeletal injuries
      sustained by elite level curling athletes during international competition. This
      study was conducted during the 2008 World Men's Curling Championships. All
      registered athletes and the tournament medical team were given report forms for
      documenting injuries that occurred during the tournament. Report form information
      included demographics, area injured, types of injuries sustained, and curling
      specific aggravating conditions. During the competition five injuries were
      reported, resulting in an injury rate of .07 injuries per game. Only one reported
      injury resulted in missed competition (.014 injuries per game). All reported
      injuries involved increased pain during curling-specific activities. At the elite
      international competitive level, injury incidence in curling was found to be low.
      Future exploration over the course of a season may be beneficial to identify risk
      factors and to assist with formulating training strategies to decrease injury
      risk.

PMID- 23541103
TI  - Characteristics of 161-km ultramarathon finishers developing exercise-associated
      hyponatremia.
AB  - This study sought to identify runner characteristics or symptoms that could
      distinguish those finishers developing exercise-associated hyponatremia (EAH)
      from those not developing EAH in a 161-km ultramarathon. Of 310 finishers, 207
      (67%) underwent postrace blood studies. Twelve (6%) finishers had EAH (blood
      sodium range 131-134 mmol/L). Experience at 161-km ultramarathons was lower (p =
      0.01) and blood creatine kinase (CK) concentration was higher (p = 0.04) among
      those with EAH than those not developing EAH. Blood sodium and CK concentration
      were negatively correlated (p = 0.0015, r = -0.22). There were no group
      differences in age, sex, regular running experience, weekly training distance,
      use of sodium supplements during training, immediately postrace sodium
      palatability and thirst ratings, body mass change, urination frequency,
      nonsteroidal anti-inflammatory drugs (NSAIDs) use, and various symptoms
      experienced during the race. These findings indicate that a clinical suspicion
      and measurement of blood sodium concentration remain the only viable means for
      determining when an ultramarathon runner has EAH.

PMID- 23541104
TI  - Influence of exercise order on muscle damage during moderate-intensity resistance
      exercise and recovery.
AB  - This study aimed to investigate the role of exercise order on total number of
      repetitions and to evaluate the possible importance on muscle damage and on
      rating perceived exertion (RPE). Ten trained participants completed two
      sequences: sequence A (SEQA) was leg press (LP), leg extension (LE), leg curl
      (LC), bench press (BP), shoulder press (SP), and triceps extension (TE) and in
      sequence B (SEQB), the order of execution of the exercises was reversed. Highest
      creatine kinase (CK) concentrations were observed 24 hours following both
      sessions, but no differences were found at any time between them, revealing that
      muscle damage has occurred. There were significant differences between SEQA and
      SEQB in the total number of repetitions for TE, LE, and LC. Our results suggest
      that differences in total strength production when exercise order is changed must
      be explained by some other mechanisms besides muscle damage and RPE.

PMID- 23541105
TI  - A comparison of COSMED metabolic systems for the determination of resting
      metabolic rate.
AB  - This study determined the reliability of measuring resting metabolic rate (RMR)
      with COSMED's FitMateTM metabolic system using a canopy dilution set-up compared
      with a previously validated COSMED QUARK CPET research-based system in 30 healthy
      adults (age: 28.4 +/- 7.0 yrs, weight: 79.9 +/- 20.2 kg, percent body fat: 22.5
      +/- 8.6%). The FitMate was developed as an inexpensive metabolic system for RMR
      and fitness testing. Subjects were randomly assigned to start testing on either
      the FitMate or Quark CPET for four 10-minute measurements. Test-retest intraclass
      correlations were 0.95-0.99, p <= 0.0001 for all parameters tested. Ve, RMR, VO2,
      and heart rate were not significantly different between the two systems. These
      results suggest that the FitMate is a reliable canopy dilution system for RMR
      measurements in healthy adults.

PMID- 23541106
TI  - Directed oxygen gradients initiate a robust early remodeling response in
      engineered vascular grafts.
AB  - Whereas functionally different, both organogenesis and wound-healing processes
      create zones or regions of hypoxia that persist until capillary networks are
      formed to facilitate oxygen and nutrient delivery. Similarly, regenerative
      processes within in vitro engineered tissues experience the same hypoxic regions,
      but without the capacity to form functional capillaries resulting in a major
      limitation in developing full-thickness organs and tissues. Due to the importance
      of oxygen in wound healing and tissue regeneration, we hypothesize that directed
      oxygen gradients can be used to modulate cell function and promote more effective
      tissue regeneration. The effect of controlled oxygen gradients on human smooth
      muscle cells (SMCs) was assessed using dual chambered perfusion bioreactors to
      regulate transport conditions occurring in a model vascular construct. SMCs were
      seeded onto the ablumenal surface of the scaffold and cultured for 21 days under
      3 independent gas environments: (1) 21% oxygen, (2) 11% oxygen, or (3) an ablumen
      to lumen oxygen gradient from 11% to 21%. When compared to 21% oxygen and 11%
      oxygen conditions, the directed 11%-21% oxygen gradient resulted in a raised
      metabolic activity and significantly improved cell migration. After 21 days from
      seeding, cells were shown to migrate entirely across the scaffold to the vessel
      lumen (>450 MUm). Concomitant with a more uniform cell dispersion, scaffold
      mechanics were significantly enhanced with increased stiffness and tensile
      strength. Native oxygen gradients are known to play a pivotal role during organ
      development; these results show that directed oxygen gradients within in vitro
      systems can be used to facilitate early remodeling leading to significantly
      enhanced cell migration and scaffold biomechanics.

PMID- 23541107
TI  - A review of adaptive mechanisms in cell responses towards oxidative stress caused
      by dental resin monomers.
AB  - Dental composite resins are biomaterials commonly used to aesthetically restore
      the structure and function of teeth impaired by caries, erosion, or fracture.
      Residual monomers released from resin restorations as a result of incomplete
      polymerization processes interact with living oral tissues. Monomers like
      triethylene glycol dimethacrylate (TEGDMA) or 2-hydroxylethyl methacrylate (HEMA)
      are cytotoxic via apoptosis, induce genotoxic effects, and delay the cell cycle.
      Monomers also influence the response of cells of the innate immune system,
      inhibit specific odontoblast cell functions, or delay the odontogenic
      differentiation and mineralization processes in pulp-derived cells including stem
      cells. These observations indicate that resin monomers act as environmental
      stressors which inevitably disturb regulatory cellular networks through
      interference with signal transduction pathways. We hypothesize that an
      understanding of the cellular mechanisms underlying these phenomena will provide
      a better estimation of the consequences associated with dental therapy using
      composite materials, and lead to innovative therapeutic strategies and improved
      materials being used at tissue interfaces within the oral cavity. Current
      findings strongly suggest that monomers enhance the formation of reactive oxygen
      species (ROS), which is most likely the cause of biological reactions activated
      by dental composites and resin monomers. The aim of the present review manuscript
      is to discuss adaptive cell responses to oxidative stress caused by monomers. The
      particular significance of a tightly controlled network of non-enzymatic as well
      as enzymatic antioxidants for the regulation of cellular redox homeostasis and
      antioxidant defense in monomer-exposed cells will be addressed. The expression of
      ROS-metabolizing antioxidant enzymes like superoxide dismutase (SOD1),
      glutathione peroxidase (GPx1/2), and catalase in cells exposed to monomers will
      be discussed with particular emphasis on the role of glutathione (GSH), which is
      the major non-enzymatic antioxidant. The causal relationship between vital cell
      functions like the regulation of cell survival or cell death in monomer-treated
      cell cultures and the availability of GSH will be highlighted. We will also
      consider the influence of monomer-induced oxidative stress on central signal
      transduction pathways including mitogen-activated protein kinases (MAPK) ERK1/2,
      p38, and JNK as well as the stress-activated transcription factors downstream Elk
      1, ATF-2, ATF-3, and cJun. Finally, we address signaling pathways originating
      from monomer-induced DNA damage including the activation of ATM (ataxia
      telangiectasia mutated), Chk2, p53, p21, and H2AX. The understanding of the
      mechanisms underlying adaptive cell responses will stimulate a constructive
      debate on the development of smart dental restorative materials which come into
      contact with oral tissues and effective strategies in dental therapy.

PMID- 23541108
TI  - Tendon healing and anti-adhesion properties of electrospun fibrous membranes
      containing bFGF loaded nanoparticles.
AB  - The ideal scaffolds should contain growth factors and thus can regulate cellular
      behaviors and tissue assembly. Electrospun fibrous membranes are widely-used
      scaffolds but growth factors are highly susceptible to losing their bioactivity
      during the electrospinning process. In this study, pre-formulated dextran glassy
      nanoparticles (DGNs) loaded with basic fibroblast growth factor (bFGF) were
      electrospun into a poly-l-lactic acid (PLLA) copolymer fiber to secure the
      bioactivity of bFGF in a sustained manner and then bioactivity retention was
      certificated by promoting cell proliferation and tendon healing. Meanwhile, the
      barrier effect of electrospun membrane was evaluated for clinic concern. In the
      in vitro release study, the protein encapsulation efficiency of the bFGF/DGNs
      PLLA membrane reached 48.71 +/- 13.53%, with a release kinetic of nearly 30 days.
      The enhanced cell proliferation and intrinsic tendon healing show that the
      bFGF/DGNs-loaded PLLA fibrous membrane can release bFGF sustainably and secure
      the bioactivity of bFGF better than the emulsion electrospun bFGF-loaded PLLA and
      PLLA fibrous membranes. Meanwhile, the anti-adhesion effect of electrospun
      membrane as barrier was fortunately combined as clinic concern.

PMID- 23541109
TI  - Therapeutic efficacy of a systemically delivered oncolytic adenovirus -
      biodegradable polymer complex.
AB  - Despite great efforts to develop a more effective oncolytic adenovirus (Ad) for
      eradicating tumors, in vivo application via systemic administration is strictly
      limited to local injection due to host immune responses by Ad surface proteins
      and liver accumulation by the inherent nature of the Ad. In the last decade,
      numerous techniques using synthetic polymers have widely emerged to shield the
      exterior of therapeutic Ad vectors for systemic delivery. We developed a cationic
      polymer linked with polyethylene glycol for systemically delivering oncolytic Ad.
      The increased transduction efficiency and oncolytic effect of the Ad vectors
      physically coated with the polymer were evaluated, showing the optimal size (130
      nm) of the Ad/polymer complex for systemic administration and prolonged stability
      of the Ad/polymer complex. Marked tumor growth suppression of the oncolytic Ad
      delivered by the polymer through systemic injection was observed in HT1080 and
      A549 xenograft models. The masking effect of the Ad surface by the polymer
      elicited evasion of innate adaptive immune responses and the tumor-to-liver ratio
      of the complex was significantly elevated 1229-fold greater than that of a naked
      Ad. These results demonstrate that the potential system of oncolytic Ad complexed
      with the biodegradable polymer may be useful for developing therapeutic vector
      systems via systemic delivery.

PMID- 23541110
TI  - Predicting the therapeutic efficacy of MSC in bone tissue engineering using the
      molecular marker CADM1.
AB  - Mesenchymal stromal cells (hMSCs) are advancing into the clinic but the
      therapeutic efficacy of hMSCs faces the problem of donor variability. In bone
      tissue engineering, no reliable markers have been identified which are able to
      predict the bone-forming capacity of hMSCs prior to implantation. To this end, we
      isolated hMSCs from 62 donors and characterized systematically their in vitro
      lineage differentiation capacity, gene expression signature and in vivo capacity
      for ectopic bone formation. Our data confirms the large variability of in vitro
      differentiation capacity which did not correlate with in vivo ectopic bone
      formation. Using DNA microarray analysis of early passage hMSCs we identified a
      diagnostic bone-forming classifier. In fact, a single gene, CADM1, strongly
      correlated with the bone-forming capacity of hMSCs and could be used as a
      reliable in vitro diagnostic marker. Furthermore, data mining of genes expressed
      correlating with in vivo bone formation represented involvement in neurogenic
      processes and Wnt signaling. We will apply our data set to predict therapeutic
      efficacy of hMSCs and to gain novel insight in the process of bone regeneration.
      Our bio-informatics driven approach may be used in other fields of cell therapy
      to establish diagnostic markers for clinical efficacy.

PMID- 23541112
TI  - [The diagnosis of rare diseases in the primary care clinic: dismantling the
      myth].

PMID- 23541111
TI  - Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet
      engraftment and function in type 1 diabetes.
AB  - Type 1 diabetes (T1DM) affects one in every 400 children and adolescents in the
      US. Due to the limitations of exogenous insulin therapy and whole pancreas
      transplantation, pancreatic islet transplantation has emerged as a promising
      therapy for T1DM. However, this therapy is severely limited by donor islet
      availability and poor islet engraftment and function. We engineered an injectable
      bio-synthetic, polyethylene glycol-maleimide hydrogel to enhance vascularization
      and engraftment of transplanted pancreatic islets in a mouse model of T1DM.
      Controlled presentation of VEGF-A and cell-adhesive peptides within this
      engineered material significantly improved the vascularization and function of
      islets delivered to the small bowel mesentery, a metabolically relevant site for
      insulin release. Diabetic mice receiving islets transplanted in proteolytically
      degradable hydrogels incorporating VEGF-A exhibited complete reversal of diabetic
      hyperglycemia with a 40% reduction in the number of islets required. Furthermore,
      hydrogel-delivered islets significantly improved weight gain, regulation of a
      glucose challenge, and intra-islet vascularization and engraftment compared to
      the clinical standard of islet infusion through the hepatic portal vein. This
      study establishes a simple biomaterial strategy for islet transplantation to
      promote enhanced islet engraftment and function.

PMID- 23541113
TI  - [The smartphone in research: the instant messenger as an ally to reduce trial
      drop-outs].

PMID- 23541114
TI  - High-dose-rate brachytherapy in symptom palliation due to malignant endobronchial
      obstruction: a quantitative assessment.
AB  - PURPOSE: This study was performed to objectively evaluate the effect of high-dose
      rate endobronchial brachytherapy (HDREB) in symptom palliation of patients with
      malignant airway obstruction and treatment-related toxicity. METHODS AND
      MATERIALS: Seventy-eight patients were treated with palliative intent according
      to a prospective observational protocol. HDREB was delivered in three fractions
      of 7.5 Gy at weekly or fortnightly intervals, associated or not with external
      beam irradiation. Most patients presented with lung cancer primaries and were
      treated because of lesions located in the trachea and/or main bronchi.
      Performance status, degree of obstruction, and symptom palliation were graded
      according to an objective score index, defined before and after HDREB at the last
      followup visit. Survival was considered from the end of HDREB for at least 3
      years or until death. RESULTS: Overall, there was a 70% improvement, with
      migration of patients from lower to higher performance status. Bronchial
      obstruction was improved in 73.4% of the patients. The symptom that presented the
      better response was hemoptysis (100% complete relief) followed by postobstructive
      pneumonia (80%), dyspnea (57.4%), and cough (33.9%). Median survival was 6 months
      and improved in patients with complete response at bronchoscopy (9 months). There
      were two (2.6%) cases of bronchial fistulae and eight cases (10.2%) of fatal
      hemoptysis. CONCLUSIONS: HDREB is an excellent modality for palliating malignant
      airway obstruction resulting in quality of life improvement, with a good
      tolerance, patient compliance, and low rate of complications.

PMID- 23541115
TI  - Tyrosine kinase signal modulation: a matter of H2O2 membrane permeability?
AB  - Abstract H2O2 produced by extracellular NADPH oxidases regulates tyrosine kinase
      signaling inhibiting phosphatases. How does it cross the membrane to reach its
      cytosolic targets? Silencing aquaporin-8 (AQP8), but not AQP3 or AQP4, inhibited
      H2O2 entry into HeLa cells. Re-expression of AQP8 with silencing-resistant
      vectors rescued H2O2 transport, whereas a C173A-AQP8 mutant failed to do so.
      Lowering AQP8 levels affected H2O2 entry into the endoplasmic reticulum, but not
      into mitochondria. AQP8 silencing also inhibited the H2O2 spikes and
      phosphorylation of downstream proteins induced by epidermal growth factor. These
      observations lead to the hypothesis that H2O2 does not freely diffuse across the
      plasma membrane and AQP8 and other H2O2 transporters are potential targets for
      manipulating key signaling pathways in cancer and degenerative diseases.

PMID- 23541116
TI  - Kinetics and thermodynamics of small molecule binding to pincer-PCP rhodium(I)
      complexes.
AB  - The kinetics and thermodynamics of the binding of several small molecules, L (L =
      N2, H2, D2, and C2H4), to the coordinatively unsaturated pincer-PCP rhodium(I)
      complexes Rh[(t)Bu2PCH2(C6H3)CH2P(t)Bu2] (1) and
      Rh[(t)Bu2P(CH2)2(CH)(CH2)2P(t)Bu2] (2) in organic solvents (n-heptane, toluene,
      THF, and cyclohexane-d12) have been investigated by a combination of kinetic
      flash photolysis methods, NMR equilibrium studies, and density functional theory
      (DFT) calculations. Using various gas mixtures and monitoring by NMR until
      equilibrium was established, the relative free energies of binding of N2, H2, and
      C2H4 in cyclohexane-d12 were found to increase in the order C2H4 < N2 < H2. Time
      resolved infrared (TRIR) and UV-vis transient absorption spectroscopy revealed
      that 355 nm excitation of 1-L and 2-L results in the photoejection of ligand L.
      The subsequent mechanism of binding of L to 1 and 2 to regenerate 1-L and 2-L is
      determined by the structure of the PCP ligand framework and the nature of the
      solvent. In both cases, the primary transient is a long-lived, unsolvated species
      (tau = 50-800 ns, depending on L and its concentration in solution). For 2, this
      so-called less-reactive form (LRF) is in equilibrium with a more-reactive form
      (MRF), which reacts with L at diffusion-controlled rates to regenerate 2-L. These
      two intermediates are proposed to be different conformers of the three-coordinate
      (PCP)Rh fragment. For 1, a similar mechanism is proposed to occur, but the LRF to
      MRF step is irreversible. In addition, a parallel reaction pathway was observed
      that involves the direct reaction of the LRF of 1 with L, with second-order rate
      constants that vary by almost 3 orders of magnitude, depending on the nature of L
      (in n-heptane, k = 6.7 * 10(5) M(-1) s(-1) for L = C2H4; 4.0 * 10(6) M(-1) s(-1)
      for L = N2; 5.5 * 10(8) M(-1) s(-1) for L = H2). Experiments in the more
      coordinating solvent, THF, revealed the binding of THF to 1 to generate 1-THF,
      and its subsequent reaction with L, as a competing pathway.

PMID- 23541117
TI  - Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal
      secretions to detect Haemophilus influenzae pneumonia.
AB  - A quantitative polymerase chain reaction (PCR) for the fucK gene was developed
      for specific detection of Haemophilus influenzae. The method was tested on sputum
      and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired
      pneumonia (CAP). With a reference standard of sputum culture and/or serology
      against the patient's own nasopharyngeal isolate, H. influenzae etiology was
      detected in 20 patients. Compared with the reference standard, fucK PCR (using
      the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity
      of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5%
      (52/58), respectively. In a receiver operating characteristic curve analysis,
      sputum fucK PCR was found to be significantly superior to sputum P6 PCR for
      detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult
      controls without respiratory symptoms. In conclusion, quantitative fucK real-time
      PCR provides a sensitive and specific identification of H. influenzae in
      respiratory secretions.

PMID- 23541118
TI  - Trends in susceptibility of selected gram-negative bacilli isolated from intra
      abdominal infections in North America: SMART 2005-2010.
AB  - This report summarizes data from the Study for Monitoring Antimicrobial
      Resistance Trends 2005-2010 to identify trends in susceptibility from intra
      abdominal infections in North America. Escherichia coli and Klebsiella pneumoniae
      were the most frequently isolated pathogens. Extended-spectrum beta-lactamase
      rates (%) in 2005/2010 for E. coli and K. pneumoniae were 1.7/7.3 and 3.2/13.1,
      respectively. Ertapenem, imipenem, amikacin, and cefoxitin showed stable
      susceptibility.

PMID- 23541120
TI  - Improving the catalytic activity of semiconductor nanocrystals through selective
      domain etching.
AB  - Colloidal chemistry offers an assortment of synthetic tools for tuning the shape
      of semiconductor nanocrystals. While many nanocrystal architectures can be
      obtained directly via colloidal growth, other nanoparticle morphologies require
      alternative processing strategies. Here, we show that chemical etching of
      colloidal nanoparticles can facilitate the realization of nanocrystal shapes that
      are topologically inaccessible by hot-injection techniques alone. The present
      methodology is demonstrated by synthesizing a two-component CdSe/CdS nanoparticle
      dimer, constructed in a way that both CdSe and CdS semiconductor domains are
      exposed to the external environment. This structural morphology is highly
      desirable for catalytic applications as it enables both reductive and oxidative
      reactions to occur simultaneously on dissimilar nanoparticle surfaces. Hydrogen
      production tests confirmed the improved catalytic activity of CdSe/CdS dimers,
      which was enhanced 3-4 times upon etching treatment. We expect that the
      demonstrated application of etching to shaping of colloidal heteronanocrystals
      can become a common methodology in the synthesis of charge-separating
      nanocrystals, leading to advanced nanoparticles architectures for applications in
      areas of photocatalysis, photovoltaics, and light detection.

PMID- 23541119
TI  - The role of glycosylated epitopes in the serodiagnosis of Strongyloides
      stercoralis infection.
AB  - Carbohydrates of pathogen antigens have been disrupted by periodate oxidation, in
      order to reduce nonspecific bindings and improve serodiagnosis of parasite
      infections. In the present study, the enzyme-linked immunosorbent assay (ELISA)
      was carried out with filariform larvae antigen treated, or not treated, with
      sodium metaperiodate. Groups of sera from patients with Strongyloides stercoralis
      infection, with other intestinal parasites and a normal control, were used. The
      oxidation of Strongyloides stercoralis glycosylated epitopes reduced the
      seroreactivity of sera from patients with S. stercoralis infection as
      demonstrated by ELISA, with a decrease in sera optical densities. The number of
      cross-reactions of IgG and IgE-ELISAs increased by 12% and 16%, respectively,
      after antigen treatment with metaperiodate. This was more often observed in
      patients infected with Schistosoma mansoni and hookworm. Moreover, the IgG
      depletion from sera tested by IgE-ELISA led to the detection of previous false
      negative samples from S. stercoralis-infected patients.

PMID- 23541121
TI  - Impact of effluent organic matter on low-pressure membrane fouling in tertiary
      treatment.
AB  - This study aims at comparing low-pressure membrane fouling obtained with two
      different secondary effluents at bench and pilot-scale based on the determination
      of two fouling indices: the total fouling index (TFI) and the hydraulically
      irreversible fouling index (HIFI). The main objective was to investigate if
      simpler and less costly bench-scale experimentation can substitute for pilot
      scale trials when assessing the fouling potential of secondary effluent in large
      scale membrane filtration plants producing recycled water. Absolute values for
      specific flux and total fouling index for the bench-scale system were higher than
      those determined from pilot-scale, nevertheless a statistically significant
      correlation (r(2) = 0.63, alpha = 0.1) was obtained for the total fouling index
      at both scales. On the contrary no such correlation was found for the
      hydraulically irreversible fouling index. Advanced water characterization tools
      such as excitation-emission matrix fluorescence spectroscopy (EEM) and liquid
      chromatography with organic carbon detection (LC-OCD) were used for the
      characterization of foulants. On the basis of statistical analysis, biopolymers
      and humic substances were found to be the major contribution to total fouling
      (r(2) = 0.95 and r(2) = 0.88, respectively). Adsorption of the low molecular
      weight neutral compounds to the membrane was attributed to hydraulically
      irreversible fouling (r(2) = 0.67).

PMID- 23541122
TI  - The neurochemistry of music.
AB  - Music is used to regulate mood and arousal in everyday life and to promote
      physical and psychological health and well-being in clinical settings. However,
      scientific inquiry into the neurochemical effects of music is still in its
      infancy. In this review, we evaluate the evidence that music improves health and
      well-being through the engagement of neurochemical systems for (i) reward,
      motivation, and pleasure; (ii) stress and arousal; (iii) immunity; and (iv)
      social affiliation. We discuss the limitations of these studies and outline novel
      approaches for integration of conceptual and technological advances from the
      fields of music cognition and social neuroscience into studies of the
      neurochemistry of music.

PMID- 23541123
TI  - Reliability of lateral distal femur dual-energy X-ray absorptiometry measures.
AB  - Dual-energy X-ray absorptiometry (DXA) of the lateral distal femur (LDF) has been
      suggested for patients with metal implants or joint contractures preventing DXA
      scanning at conventional anatomical sites. This study assessed variability in LDF
      DXA measures due to repeat scanning using data from 5 healthy young adults who
      had 3 unilateral scans with repositioning between scans. Variability due to image
      analysis was evaluated in 10 children who underwent bilateral LDF scans with each
      scan being analyzed 3 times by 2 raters. Regions of interest (ROIs) were defined
      in the anterior distal metaphysis (R1), metadiaphysis (R2), and diaphysis (R3) as
      described previously. An additional region (R4) was defined in the metaphysis
      similar to R1 but centered in the medullary canal. Variability was consistently
      lower for bone mineral density than for bone mineral content and bone area; R4
      was more repeatable than R1; and variability because of repeat scanning was
      negligible. These results suggest that DXA measures of the LDF are reliable and
      may be useful when standard DXA measures cannot be obtained, but it is
      recommended that a central, rather than anterior, ROI be used in the metaphysis. 

PMID- 23541124
TI  - Normative data of body fat mass and its distribution as assessed by DXA in Indian
      adult population.
AB  - Dual-energy X-ray absorptiometry (DXA) assessment of body fat mass is precise and
      highly correlated with under water weighing. In view of ethnic differences, we
      undertook this study to prepare normative data for body fat mass in apparently
      healthy adult Indians and correlate it with body mass index (BMI). This cross
      sectional population-based study included 2347 subjects (male: 924; female: 1423)
      aged >20 yr who participated in a general health examination. They were evaluated
      for anthropometry and body fat mass by DXA. All subjects were categorized as
      overweight and obese based on standard BMI criteria. Mean age and BMI were 49.1
      +/- 18.2yr and 25.0 +/- 4.7kg/m(2), respectively. Mean percent total and regional
      fat (trunk, arm, and leg) reached maximum in the age group of 30-40yr in males
      and 50-60yr in females. Females had significantly higher total and regional fat
      mass compared with males. Fat mass was positively correlated with age (r = 0.224;
      p < 0.00001) and BMI (r = 0.668; p < 0.00001). Prevalence of overweight and
      obesity was seen in 2119 (46.1%) and 536 (13.8%), respectively, according to
      World Health Organization definition and 64.0% and 31.1%, respectively, as per
      Indian guidelines. Percent total body fat mass (PTBFM) of 25% in males and 30% in
      females corresponds to BMI of 22.0kg/m(2) with sensitivity of >80% and
      specificity of >70% in receiver operating characteristic curve analysis. Body fat
      mass in Indians is higher than that in Western populations for a given age and
      BMI. PTBFM of 25% in males and 30% in females corresponds to BMI of 22kg/m(2) in
      Indians.

PMID- 23541126
TI  - Cytochrome P450 2D6 phenoconversion is common in patients being treated for
      depression: implications for personalized medicine.
AB  - OBJECTIVE: Determine the point prevalence of phenoconversion to cytochrome P450
      2D6 (CYP2D6) poor metabolizer status in clinical practice. METHOD: This
      multicenter, open-label, single-visit naturalistic study was conducted from
      October 2008 to July 2009 in adult patients (>= 18 years) who had been receiving
      venlafaxine extended-release (ER) (37.5-225 mg/d) treatment for up to 8 weeks. A
      15-mL blood sample was drawn 4 to 12 hours after patients' last venlafaxine ER
      dose. Plasma O-desmethylvenlafaxine and venlafaxine concentrations were
      determined for each patient. CYP2D6 poor metabolizer phenotype was defined as O
      desmethylvenlafaxine to venlafaxine ratio < 1 based on published data. CYP2D6
      genotype was determined for each patient; patients were classified as poor
      metabolizer, intermediate metabolizer, extensive metabolizer, and ultrarapid
      metabolizer. Agreement between poor metabolizer phenotype and genotype
      classifications was assessed using the McNemar test. RESULTS: Phenoconversion to
      CYP2D6 poor metabolizer status occurred in 209 of 865 individuals (24%) with a
      CYP2D6 non-poor metabolizer genotype. The incidence of CYP2D6 poor metabolizer
      status based on phenotype was almost 7 times higher than that expected based on
      genotype: only 4% (35/900) of patients were genotypic CYP2D6 poor metabolizers,
      but 27% (243/900) were phenotypic CYP2D6 poor metabolizers (McNemar test, P <
      .0001). CONCLUSIONS: CYP2D6 phenotype conversion is common in patients being
      treated for depression. These results are important because differences in CYP2D6
      drug metabolic capacity, whether genetically determined or due to
      phenoconversion, can affect clinical outcomes in patients treated with drugs
      substantially metabolized by CYP2D6. These results demonstrate that personalized
      medicine based solely on genetics can be misleading and support the need to
      consider drug-induced variability as well. TRIAL REGISTRATION: ClinicalTrials
      identifier: NCT00788944.

PMID- 23541125
TI  - Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by
      wood smoke particulate material.
AB  - Cigarette smoke, diesel exhaust, and other combustion-derived particles activate
      the calcium channel transient receptor potential ankyrin-1 (TRPA1), causing
      irritation and inflammation in the respiratory tract. It was hypothesized that
      wood smoke particulate and select chemical constituents thereof would also
      activate TRPA1 in lung cells, potentially explaining the adverse effects of wood
      and other forms of biomass smoke on the respiratory system. TRPA1 activation was
      assessed using calcium imaging assays in TRPA1-overexpressing HEK-293 cells,
      mouse primary trigeminal neurons, and human adenocarcinoma (A549) lung cells.
      Particles from pine and mesquite smoke were less potent agonists of TRPA1 than an
      equivalent mass concentration of an ethanol extract of diesel exhaust particles;
      pine particles were comparable in potency to cigarette smoke condensate, and
      mesquite particles were the least potent. The fine particulate (PM < 2.5 MUm) of
      wood smoke were the most potent TRPA1 agonists and several chemical constituents
      of wood smoke particulate, 3,5-ditert-butylphenol, coniferaldehyde, formaldehyde,
      perinaphthenone, agathic acid, and isocupressic acid, were TRPA1 agonists. Pine
      particulate activated TRPA1 in mouse trigeminal neurons and A549 cells in a
      concentration-dependent manner, which was inhibited by the TRPA1 antagonist HC
      030031. TRPA1 activation by wood smoke particles occurred through the
      electrophile/oxidant-sensing domain (i.e., C621/C641/C665/K710), based on the
      inhibition of cellular responses when the particles were pretreated with
      glutathione; a role for the menthol-binding site of TRPA1 (S873/T874) was
      demonstrated for 3,5-ditert-butylphenol. This study demonstrated that TRPA1 is a
      molecular sensor for wood smoke particulate and several chemical constituents
      thereof, in sensory neurons and A549 cells, suggesting that TRPA1 may mediate
      some of the adverse effects of wood smoke in humans.

PMID- 23541128
TI  - Response to the letter to the editor.

PMID- 23541129
TI  - Is acetaminophen more prone to biliary excretion given orally than rectally in
      infants?

PMID- 23541130
TI  - Plasma exchange for steroid-refractory relapses in multiple sclerosis: an
      observational, MRI pilot study.
AB  - BACKGROUND: Numerous studies have shown that plasma exchange (PE) is effective as
      second-line treatment of severe exacerbations of multiple sclerosis (MS) or other
      idiopathic inflammatory demyelinating diseases of the central nervous system that
      are nonresponsive to steroid therapy. OBJECTIVE: The goal of this study was to
      analyze the effect of PE on clinically active radiologic lesions in steroid
      refractory relapses of MS and idiopathic inflammatory demyelinating diseases of
      the central nervous system. METHODS: This was a prospective, observational pilot
      study in which the primary end point was the degree of radiologic resolution of
      active lesions after PE. RESULTS: A total of 15 patients were included (median
      age, 36.9 years [age range, 21-67 years]; 60% women). Five (33.3%) of the 15
      patients had relapsing-remitting MS, 2 (13.3%) had clinically isolated syndrome
      that presented with transverse myelitis, 2 (13.3%) had recurrent myelitis, 1
      (6.7%) had transverse myelitis, 1 (6.7%) had longitudinally extensive transverse
      myelitis, 1 (6.7%) had acute disseminated encephalomyelitis, 1 (6.7%) had Balo's
      concentric sclerosis, and 2 (13.3%) had neuromyelitis optica. Mean increase on
      the expanded disability status scale scores due to relapses was 4.8 (2.53). After
      PE, 93.3% showed a marked to moderate clinical improvement, and 46.7% recovered
      their baseline expanded disability status scale score 3 months post-PE. On the
      post-PE MRI, 60% showed radiologic resolution (80% mass-effect lesions, 83.3% new
      onset disease, and 100% neuromyelitis optica), 20% had partial resolution, and
      20% no resolution. A significant relationship was not obtained between degree of
      resolution of radiologic lesions and the variables: clinical response to PE, new
      onset disease, mass-effect lesions, number of PE sessions, and early initiation
      of PE. CONCLUSION: A marked to moderate clinical improvement post-PE accompanied
      by a lack of radiologic resolution of the active lesion is not indicative of poor
      prognosis.

PMID- 23541131
TI  - Patient characteristics predicting the frequency of medication therapy management
      visits for patients with diabetes.
AB  - BACKGROUND: Patient characteristics associated with a higher exposure to
      medication therapy management (MTM) and the relationship between frequency of MTM
      visits and meeting clinically defined goals of therapy have not been documented.
      OBJECTIVE: The goal of this study was to evaluate factors predicting frequency of
      MTM visits for patients with diabetes and the impact of these visits on diabetes
      clinical outcomes. METHODS: All patients with diabetes participating in a 2007
      MTM demonstration project (N = 121) were included in the analysis. A negative
      binomial regression controlling for age, sex, presence of diabetes complications,
      taking insulin, Charlson score Index, and hypertension and cholesterol medication
      regimen composition was used to assess predictors of the number of MTM visits.
      Optimal diabetes management differences between the 2 groups defined according to
      median number of MTM visits (low frequency, <=4; high frequency, >4) was compared
      by using Wilcoxon Mann-Whitney and chi(2) tests. RESULTS: Having diabetes
      complications (relative risk = 2.83 [95% CI, 1.3-6.17]; P = 0.0088) and taking
      insulin (relative risk = 1.43 [95% CI, 1.12-1.83]; P = 0.0038) were associated
      with a higher number of MTM visits. At baseline, the high-frequency group had a
      significantly higher proportion of patients with insulin therapy (P < 0.01),
      higher proportion with diabetes complications (P = 0.07), and higher mean
      Charlson score (P = 0.08). The rate of optimal diabetes care was significantly
      lower in the high-frequency group before MTM (P = 0.02) but not statistically
      different from the low-frequency group during and 1 year after the demonstration
      project. CONCLUSIONS: Patients with diabetes complications and using regimens
      that include insulin received more frequent MTM visits. MTM services delivered to
      a diabetes population with more complex disease or taking insulin have a positive
      impact on optimal diabetes care.

PMID- 23541132
TI  - Can pragmatic trials help us better understand chronic pain and improve
      treatment?

PMID- 23541133
TI  - Crystal chemistry, band engineering, and photocatalytic activity of the LiNb3O8
      CuNb3O8 solid solution.
AB  - A new solid solution has been prepared in the system LiNb3O8-CuNb3O8, and the
      impacts of chemical composition and crystal structure have been investigated for
      the resulting band gap sizes and photocatalytic activities for water reduction to
      hydrogen under visible light. All members of the solid solution were synthesized
      by solid-state methods within evacuated fused-silica vessels, and their phase
      purities were confirmed via powder X-ray diffraction techniques (space group
      P2(1)/a, a = 15.264(5)-15.367(1) A, b = 5.031(3)-5.070(1) A, c = 7.456(1)
      7.536(8) A, and beta = 107.35(1)-107.14(8) degrees , for 0 <= x <= 1). Rietveld
      refinements were carried out for the x = 0.09, 0.50, and 0.70 members of the
      solid solution, which reveal the prevailing isostructurality of the continuous
      solid solution. The structure consists of chains of (Li/Cu)O6 and NbO6 octahedra.
      The optical band gap size across the solid solution exhibits a significant red
      shift from ~3.89 eV (direct) to ~1.45 eV and ~1.27 eV (direct and indirect) with
      increasing Cu(I) content, consistent with the change in sample color from white
      to dark brown to black. Electronic structure calculations based on density
      functional theory methods reveal the rapid formation of a new Cu 3d(10)-based
      valence band that emerges higher in energy than the O 2p band. While the pure
      LiNb3O8 is a highly active UV-photocatalyst for water reduction, the Li(1
      x)Cu(x)Nb3O8 solid is shown to be photocatalytically active under visible-light
      irradiation for water reduction to hydrogen.

PMID- 23541135
TI  - Distress, need for help, and positive feelings derived from participation in sex
      research: findings of a population study in The Netherlands.
AB  - To inform cost-benefit analyses of potential harms and benefits for participants
      in sex research, the current study investigated potential effects of completing a
      self-report sex survey. The data stem from a sexual health study in a population
      sample in the Netherlands (N = 8,064; 15 to 70 years old). Three measures
      assessed potential effects of participation: distress, need for help, and
      positive feelings related to research participation. Analyses showed that levels
      of experienced distress and need for help resulting from participation in a self
      report sex survey were low, while participants reported positive feelings to a
      considerable extent. Only few participants reported levels of positive
      experiences that were lower than the levels of distress (4.8%) or need for help
      (1.7%) they experienced. Although differences were found according to
      sociodemographic characteristics and sexual experiences, the proportion of
      variance explained by these variables was generally small. While the findings of
      this study show that the balance between potential harm and positive outcomes
      seems disturbed for few participants, researchers should provide participants
      with the details of care providers in case they experience any distress or need
      for help. 

PMID- 23541136
TI  - The challenges of service provision in younger-onset dementia.

PMID- 23541134
TI  - Dynamic manipulation of hydrogels to control cell behavior: a review.
AB  - For many tissue engineering applications and studies to understand how materials
      fundamentally affect cellular functions, it is important to have the ability to
      synthesize biomaterials that can mimic elements of native cell-extracellular
      matrix interactions. Hydrogels possess many properties that are desirable for
      studying cell behavior. For example, hydrogels are biocompatible and can be
      biochemically and mechanically altered by exploiting the presentation of cell
      adhesive epitopes or by changing hydrogel crosslinking density. To establish
      physical and biochemical tunability, hydrogels can be engineered to alter their
      properties upon interaction with external driving forces such as pH, temperature,
      electric current, as well as exposure to cytocompatible irradiation.
      Additionally, hydrogels can be engineered to respond to enzymes secreted by
      cells, such as matrix metalloproteinases and hyaluronidases. This review details
      different strategies and mechanisms by which biomaterials, specifically
      hydrogels, can be manipulated dynamically to affect cell behavior. By employing
      the appropriate combination of stimuli and hydrogel composition and architecture,
      cell behavior such as adhesion, migration, proliferation, and differentiation can
      be controlled in real time. This three-dimensional control in cell behavior can
      help create programmable cell niches that can be useful for fundamental cell
      studies and in a variety of tissue engineering applications. 

PMID- 23541137
TI  - Predicting functional decline of older men living in veteran homes by minimum
      data set: implications for disability prevention programs in long term care
      settings.
AB  - OBJECTIVE: To evaluate the risk and protective factors for functional decline of
      veteran home residents in Taiwan to develop disability prevention programs in
      long term care settings. DESIGN: A prospective cohort study. SETTING: Two veteran
      homes in Taiwan. PARTICIPANTS: A total of 1045 residents of veteran homes.
      INTERVENTION: None. MEASUREMENTS: Minimum data set (MDS), resident assessment
      protocols (RAP), MDS-COGS, Resource Utilization Group-III Activities of Daily
      Living scale, MDS Social engagement scale, MDS Pain scale. RESULTS: A total of
      1045 (83.0 +/- 5.1 years, all men) residents completed the study, and 11.3% of
      them developed significant functional decline during the study period.
      Participants with long-term institutionalization history (odds ratio [OR] 2.966,
      confidence interval [CI] 1.270-6.927), underlying cerebrovascular disease (OR
      4.432, CI 1.994-9.852) and dementia (OR 2.150, CI 1.029-4.504), and higher sum of
      RAP triggers (OR 1.366, CI 1.230-1.517) were more likely to develop functional
      decline, whereas those who had better social engagement were significantly
      protective from functional decline (OR 0.528, CI 0.399-0.697). CONCLUSIONS:
      Cerebrovascular disease, dementia, higher sum of RAP triggers, and long-term
      institutionalization were independent risk factors for functional decline,
      whereas better social engagement had a protective effect on functional
      dependence. Further study is needed to develop an integrated disability
      prevention program based on the discoveries of this study.

PMID- 23541138
TI  - Bromeliothrix metopoides, a boom and bust ciliate (Ciliophora, Colpodea) from
      tank bromeliads.
AB  - We investigated the recently described colpodid ciliate Bromeliothrix metopoides
      in a series of laboratory experiments to reveal the environmental factors that
      constrain this species to its peculiar habitat, i.e. the tanks of bromeliads. Our
      results demonstrated that the various life stages of this ciliate (bacterivorous
      theronts and microstome trophonts, flagellate-feeding macrostomes) have specific
      demands in terms of food quality and quantity. Bromeliothrix required a high food
      threshold (>1.4 mg CL(-1)) in order to thrive. Food quality also affected resting
      cyst formation of B. metopoides when the experimental containers dried out. Its
      maximum growth rates (MUmax=4.71 d(-1), i.e., 6.8 doublings d(-1)) belong to the
      highest ones recorded thus far for free-living ciliates. The pH niche of B.
      metopoides was relatively wide (pH ~4 to >9) under optimal food conditions.
      However, its high sensitivity to unfavourable environmental conditions let the
      population collapse within several hours. We conclude that B. metopoides is a
      boom and bust ciliate that is specifically adapted to its peculiar habitat but
      virtually unviable in other environments.

PMID- 23541139
TI  - [Temporal arteritis: a field of research perspective].

PMID- 23541140
TI  - [Hoigne syndrome following an intravenous injection of ceftriaxone: a case
      report].
AB  - INTRODUCTION: Hoigne's syndrome is characterized by the development of acute
      clinical manifestations which are mainly psycho-sensorial. Classically, these
      features immediately follow the injection of procaine penicillin G. CASE REPORT:
      We report a 59-year-old man who presented with psycho-organic manifestations that
      occurred just after the intravenous injection of ceftriaxone; to our knowledge,
      this is the first case of Hoigne's syndrome reported after an injection of this
      antibiotic. CONCLUSION: The pathophysiologic basis of this syndrome is still
      unknown. It is important to keep in mind its clinical characteristics, which may
      mimic immuno-allergic symptoms. It should be differentiated from anaphylactic
      manifestations because Hoigne's syndrome allows the continuation of the
      treatment.

PMID- 23541141
TI  - [Severe cholestatic hepatitis revealing a DRESS syndrome].
AB  - INTRODUCTION: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome
      is a drug-induced hypersensitivity syndrome, characterized by rash,
      hyereosinophilia and multiorgan failure, including cytolytic hepatitis. CASE
      REPORT: A 75-year-old man, treated with amoxicillin/clavulanic acid, presented
      with jaundice and disabling pruritus associated with severe cholestatic
      hepatitis, related to a DRESS syndrome. Because of the persistence of cholestasis
      and the severity of pruritus, a treatment with corticosteroids and plasma
      exchanges was initiated, allowing a rapid and complete remission. CONCLUSION:
      Amoxicillin/clavulanic acid, although rarely described in the literature, is a
      rare cause of DRESS syndrome. Severe cholestatic hepatitis associated with
      disabling pruritus may be one of the systemic manifestations, with a good
      prognosis using corticosteroids and plasma exchanges.

PMID- 23541142
TI  - Oxidative stress and neurodegeneration.

PMID- 23541143
TI  - [Evaluation of functional remission in schizophrenic disorder. The FROGS Scale].
AB  - INTRODUCTION: Functional remission is an important treatment goal in
      schizophrenia, as independent living and reintegration of patients into the
      community is the ultimate goal of any treatment. Nevertheless, assessing
      functional remission in schizophrenia is problematic, as it is a multifactorial
      entity reflecting various aspects such as symptoms severity, personal skills and
      sociocultural expectancies. METHOD: The purpose of this study was to create and
      validate a novel scale for the evaluation of functional remission in
      schizophrenia. Unlike previous scales, this one was built on the basis of
      patients with few schizophrenia symptoms. The "Functional Remission of General
      Schizophrenia" (FROGS) scale was developed using the expert consensus method
      following a MEDLINE and standard database search. Out of the 61 initially
      proposed, 19 items were selected as gathering the core aspects of functional
      remission in schizophrenia detected in the literature. The FROGS was then
      evaluated in 432 patients with DSM-IV criteria of schizophrenia, all of them
      meeting Andreasen's symptomatic remission criteria. Such an instrument should
      have a stable structure over time but also be able to detect improvement in
      functioning with time. So we have further analysed the validity of the FROGS
      scale, specifically assessing time stability. We re-evaluated the initial patient
      sample around 1.5 years after the first evaluation (mean=17.1 months +/- 1.9),
      restricting the analyses to patients who were still being followed-up and in
      clinical remission (n=140). RESULTS: Total score was highly reliable. Exploratory
      factor analysis after oblique rotation revealed that a three-factor solution was
      the most meaningful. On the basis of item content these three factors were
      labelled 'Social Functioning', 'Daily Life' and 'Treatment'. The FROGS total
      score can be used to measure a general construct for the evaluation of functional
      remission in schizophrenia. The mean FROGS total score was 75.8 (sd=10.8) at the
      second evaluation showing a significant improvement with time (3.8; P<0.0001
      versus the first evaluation). The internal consistency/reliability of the FROGS
      scale was still very high (Cronbach's alpha=0.919). Significant improvement
      between the first and second evaluation were also apparent for all the individual
      items in the FROGS scale (P<0.01) as well as for the subscores for three
      extracted factors (P<0.0001). Statistically significant correlations were
      observed between the FROGS scale and other indices, including the Global
      Assessment of functioning (r=0.58; P<0.0001). These results provide further
      evidence of the solid psychometric properties of the FROGS scale.
      DISCUSSION/CONCLUSION: The results of these two validation studies provide
      further evidence of the scale's utility and its solid psychometric properties.
      Furthermore, it is sensitive to the duration of clinical remission. Our scale may
      be a step towards developing a consensual definition of functional remission in
      schizophrenia.

PMID- 23541144
TI  - Morphological evolution of Si nanowires upon lithiation: a first-principles
      multiscale model.
AB  - Silicon is a promising anode material for high-capacity Li-ion batteries. Recent
      experiments show that lithiation of crystalline silicon nanowires leads to highly
      anisotropic morphologies. This has been interpreted as due to anisotropy in
      equilibrium interface energies, but this interpretation does not capture the
      dynamic, nonequilibrium nature of the lithiation process. Here, we provide a
      comprehensive explanation of experimentally observed morphological changes, based
      on first-principles multiscale simulations. We identify reaction paths and
      associated structural transformations for Li insertion into the Si {110} and
      {111} surfaces and calculate the relevant energy barriers from density functional
      theory methods. We then perform kinetic Monte Carlo simulations for nanowires
      with surfaces of different orientations, which reproduce to a remarkable degree
      the experimentally observed profiles and the relative reaction front rates.

PMID- 23541145
TI  - Ketamine, magnesium and major depression--from pharmacology to pathophysiology
      and back.
AB  - The glutamatergic mechanism of antidepressant treatments is now in the center of
      research to overcome the limitations of monoamine-based approaches. There are
      several unresolved issues. For the action of the model compound, ketamine, NMDA
      receptor block, AMPA-receptor activation and BDNF release appear to be involved
      in a mechanism, which leads to synaptic sprouting and strengthened synaptic
      connections. The link to the pathophysiology of depression is not clear. An
      overlooked connection is the role of magnesium, which acts as physiological NMDA
      receptor antagonist: 1. There is overlap between the actions of ketamine with
      that of high doses of magnesium in animal models, finally leading to synaptic
      sprouting. 2. Magnesium and ketamine lead to synaptic strengthening, as measured
      by an increase in slow wave sleep in humans. 3. Pathophysiological mechanisms,
      which have been identified as risk factors for depression, lead to a reduction of
      (intracellular) magnesium. These are neuroendocrine changes (increased cortisol
      and aldosterone) and diabetes mellitus as well as Mg(2+) deficiency. 4. Patients
      with therapy refractory depression appear to have lower CNS Mg(2+) levels in
      comparison to health controls. 5. Experimental Mg(2+) depletion leads to
      depression- and anxiety like behavior in animal models. 6. Ketamine, directly or
      indirectly via non-NMDA glutamate receptor activation, acts to increase brain
      Mg(2+) levels. Similar effects have been observed with other classes of
      antidepressants. 7. Depressed patients with low Mg(2+) levels tend to be therapy
      refractory. Accordingly, administration of Mg(2+) either alone or in combination
      with standard antidepressants acts synergistically on depression like behavior in
      animal models. CONCLUSION: On the basis of the potential pathophysiological role
      of Mg(2+)-regulation, it may be possible to predict the action of ketamine and of
      related compounds based on Mg(2+) levels. Furthermore, screening for compounds to
      increase neuronal Mg(2+) concentration could be a promising instrument to
      identify new classes of antidepressants. Overall, any discussion of the
      glutamatergic system in affective disorders should consider the role of Mg(2+).

PMID- 23541146
TI  - Polycyclic aromatic hydrocarbons in lung tissue of patients with pulmonary cancer
      from Romania. Influence according as demographic status and ABO phenotypes.
AB  - The lung is a target organ for the toxic effects of several chemical agents,
      including natural products, industrial chemicals, environmental agents, and
      occasionally, drugs. The assessment of PAHs in the lungs of patients with
      pulmonary cancer is important because these pollutants have mutagenic,
      carcinogenic and endocrine-disrupting properties. This study included 31
      histological confirmed lung cancer cases diagnosed consecutively at the Clinical
      Hospital of Pneumology (Iasi, Romania) from 2008 to 2009. Analyses were carried
      out using an accelerated solvent extraction technique and HPLC with a
      fluorescence detector. Fifteen PAHs were detected in all analyzed samples with
      non-carcinogenic compounds significantly elevated (45.57 ng g(-1) wet tissue)
      against carcinogenic compounds (6.12 ng g(-1) wet tissue). The mean +/- SD lung
      tissue level of benzo(a)anthracene (3.57 +/- 4.64 ng g(-1) wet tissue), a
      carcinogenic PAH, was found to be significantly higher (p<0.05) in patients from
      urban areas compared with the level (1.22 +/- 1.45 ng g(-1) wet tissue) in
      patients from rural areas. Similarly, the levels of non-carcinogenic acenaphtene
      (8.95 +/- 13.32 ng g(-1) wet tissue), fluoranthrene (5.31 +/- 5.40 ng g(-1) wet
      tissue) and anthracene (4.83 +/- 7.57 ng g(-1) wet tissue) were also detected to
      be higher (p<0.05) in the urban group compared to the levels for the rural group
      (1.46 +/- 2.34, 1.83 +/- 2.50 and 1.89 +/- 3.79 ng g(-1) wet tissue,
      respectively). High concentrations of PAHs, especially carcinogenic PAHs, such as
      benzo(a)pyrene, benzo(a)anthracene, benzo(b)fluoranthrene, and
      benzo(k)fluoranthrene, were observed in lung tissue samples collected from
      subjects with A and O blood types.

PMID- 23541147
TI  - Do differences in sensitivity between native and invasive amphipods explain their
      coexistence in Lake Constance? A case study with lambda-cyhalothrin.
AB  - Invasive species are considered as one of the major threats for biodiversity
      worldwide. The Ponto-Caspian species Dikerogammarus villosus, for instance,
      spread throughout continental Europe and was recorded for the first time also
      within Lake Constance in 2003. Although D. villosus is a highly competitive
      species it was not capable of replacing the native Gammarus roeselii completely
      in this ecosystem, especially in the riparian zones of the highly agriculturally
      used island "Reichenau". As differences in pesticide sensitivity between both
      amphipod species may explain their distribution, the present study assessed the
      implication of the highly toxic pyrethroid lambda-cyhalothrin, which is
      authorized for application in the Lake Constance region, assuming the invasive
      species being more sensitive than the native one. However, both the feeding
      activity bioassays, which measured the leaf consumption over 7d (n=20), as well
      as the predation bioassay, which measured the predation rate upon Baetis nymphs
      in concert with the feeding activity on leaf material over 96 h (n=13), revealed
      an up to 5-fold higher tolerance of D. villosus towards lambda-cyhalothrin. These
      results suggest the investigated insecticide not being the trigger for the
      observed distribution pattern of both amphipod species. Hence, other factors like
      the diversity of habitat structures or the levels of ammonia may have facilitated
      the coexistence. Nevertheless, the present study uncovered a high leaf-shredding
      efficacy of the invasive species D. villosus suggesting that its role in the leaf
      decomposition process may have been underestimated in the past.

PMID- 23541148
TI  - Photocatalytic degradation of tetracycline in aqueous solution by nanosized TiO2.
AB  - Tetracyclines are widely-used antibiotics in the world. Due to their poor
      absorption by human beings, or poultry and livestocks, most of them are excreted
      into the environment, causing growing concern about their potential impact, while
      photodegradation has been found to dominate their sequestration and
      bioavailability. Coupling with high-performance liquid chromatography-mass
      spectroscopy (HPLC-MS), gas chromatography-mass spectroscopy (GC-MS) and electron
      spin resonance (ESR), the mechanism of photocatalytic degradation of TC in
      aqueous solution by nanosized TiO2 (P25) under UV irradiation was investigated.
      The photocatalysis eliminated 95% of TC and 60% of total organic carbon (TOC)
      after 60 min irradiation, and NH4(+) ion was found to be one of the end-products.
      Bioluminescence assay showed that the toxicity of TC solution reached the maximum
      after 20 min irradiation and then gradually decreased. The degradation of TC
      included electron transfer, hydroxylation, open-ring reactions and cleavage of
      the central carbon. A possible photocatalytic degradation pathway of TC was
      proposed on the basis of the identified intermediates. Overall, the TiO2
      photocatalysis was found to be a promising process for removing TC and its
      intermediates.

PMID- 23541149
TI  - Fate of 90Sr and U(VI) in Dounreay sediments following saline inundation and
      erosion.
AB  - There is concern that sea level rise associated with projected climate change
      will lead to the inundation, flooding and erosion of soils and sediments
      contaminated with radionuclides at coastal nuclear sites, such as Dounreay (UK),
      with seawater. Here batch and column experiments were designed to simulate these
      scenarios and sequential extractions were used to identify the key radionuclide
      solid phase associations. Strontium was exchangeable and was mobilised rapidly by
      ion exchange with seawater Mg(2+) in both batch and column experiments. In
      contrast, U was more strongly bound to the sediments and mobilisation was
      initially limited by the influence of the sediment on the pH of the water.
      Release was only observed when the pH increased above 6.9, suggesting that the
      formation of soluble U(VI)-carbonate species was important. Under dynamic flow
      conditions, long term release was significant (47%), but controlled by slow
      desorption kinetics from a range of binding sites. 

PMID- 23541150
TI  - An exploration of the follow-up up needs of patients with inflammatory bowel
      disease.
AB  - BACKGROUND AND AIMS: The rising incidence of inflammatory bowel disease (IBD) in
      adults and children has implications for the lifelong burden of disease and the
      provision of specialist services. Patients with IBD should have access to
      specialist care which is delivered according to their values and needs. Few
      studies have examined patients' views of follow-up care. The aim of this
      qualitative study was to explore patients' needs, preferences and views of follow
      up care. METHODS: IBD patients were selected from a gastroenterology clinic in a
      UK Hospital and invited to participate in interviews which focused on needs,
      preferences and role of follow-up, their experience of follow-up, service
      delivery, and other models of follow-up care. RESULTS: 24 patients were
      recruited, 18 patients had Crohn's Disease, and 6 ulcerative colitis. Median age
      was 48.5 years (range was 27-72 years) and median disease duration 11.5 years
      (range 2-40 years). Four main themes emerged: (1) experiences of current follow
      up care; (2) attitudes to new models of care, including self-management, role of
      general practitioner, patient-initiated consultations and 'virtual' follow-up;
      (3) the personal value of follow-up care; and (4) the 'ideal' consultation.
      CONCLUSION: The main finding was that patients prefer a more flexible follow-up
      care system. 'Virtual' care as an adjunct to patient-initiated consultations and
      self-management, was identified as optimal approaches to meet the patients' needs
      of follow-up care. New models of follow-up care could improve the patients'
      experience of care, offer potential cost savings with reduction in face-to-face
      consultations and allow targeted care to those who need it.

PMID- 23541151
TI  - Systematic review of clofazimine for the treatment of drug-resistant
      tuberculosis.
AB  - The increased incidence of drug-resistant tuberculosis has created an urgent
      necessity for the development of new and effective anti-tuberculosis drugs and
      for alternative therapeutic regimens. Clofazimine (CFZ) is a fat-soluble
      riminophenazine dye used in the treatment of leprosy worldwide. CFZ has also been
      used as a Group 5 drug in the treatment of tuberculosis (TB). A large cohort
      study from Bangladesh published in 2010 described a treatment regimen for
      multidrug-resistant tuberculosis (MDR-TB) including CFZ as being highly effective
      against MDR-TB. We searched multiple databases for studies published through
      February 2012 that reported use of CFZ in MDR- and extensively drug-resistant TB
      (XDR-TB) treatment regimens. We identified nine observational studies (6 MDR-TB
      and 3 XDR-TB) including patients with drug-resistant TB treated with CFZ.
      Overall, 65% (95% confidence interval [95%CI] 54-76) of the patients experienced
      favorable outcomes, defined as either cure or treatment completion. Using random
      effects meta-analysis, 65% (95%CI 52-79) of those with MDR-TB and 66% (95%CI 42
      89) of those with XDR-TB experienced favorable treatment outcomes. High-quality
      prospective cohort studies and clinical trials examining the effect of CFZ as
      part of drug-resistant TB treatment regimens are needed. 

PMID- 23541152
TI  - Implicit sequence learning and working memory: correlated or complicated?
AB  - The relationship between implicit/incidental sequence learning and working memory
      motivated a series of research because it is plausible that higher working memory
      capacity opens a "larger window" to a sequence, allowing thereby the sequence
      learning process to be easier. Although the majority of studies found no
      relationship between implicit sequence learning and working memory capacity, in
      the past few years several studies have tried to demonstrate the shared or partly
      shared brain networks underlying these two systems. In order to help the
      interpretation of these and future results, in this mini-review we suggest the
      following factors to be taken into consideration before testing the relationship
      between sequence learning and working memory: 1) the explicitness of the
      sequence; 2) the method of measuring working memory capacity; 3) online and
      offline stages of sequence learning; and 4) general skill- and sequence-specific
      learning. 

PMID- 23541153
TI  - Development of an ion-exchange chromatography method for monitoring the
      degradation of prebiotic arabinoxylan-oligosaccharides in a complex fermentation
      medium.
AB  - Arabinoxylan-oligosaccharides (AXOS) are a new class of prebiotics with promising
      health-promoting characteristics. However, the mechanism by which bacteria break
      down these compounds in the colon is still uncharacterized, due to their
      structural complexity. A new analytical method that offers structural information
      was developed to characterize AXOS degradation during fermentation. The method
      was based on the simultaneous determination of arabinose, xylose, xylo
      oligosaccharides (XOS), and AXOS by applying high-performance anion-exchange
      chromatography with pulsed amperometric detection. To study the structural
      features of AXOS in solution without the use of spectroscopic techniques or
      standards, enzymatic-based reference degradation chromatograms were generated
      based on enzymes with known specificity. The new method for fingerprinting showed
      to be a powerful and fast tool to study AXOS degradation with high repeatability
      with respect to peak area, peak width at half height, and retention time
      (respective relative standard deviations of <=3.1%, 2.8%, and 0.8%). This method
      was successfully applied to study the degradation kinetics of AXOS in a complex
      fermentation medium by Bifidobacterium longum LMG 11047. The results showed that
      this strain could use both the arabinose side chains and xylose backbones up to
      xylotetraose. The characterization of the degradation abilities of AXOS by colon
      bacteria will allow a better understanding of the beneficial effects of these
      prebiotics. Furthermore, if the appropriate enzymes are available to design the
      reference degradation chromatograms, this new method for the qualitative
      fingerprinting of AXOS breakdown can also be applied for the breakdown of other
      complex oligosaccharides and polysaccharides.

PMID- 23541158
TI  - Wound healing at adaptation zones of skin flaps harvested from acute burned skin.
AB  - BACKGROUND: Early reconstruction of burn defects culminates in more successful
      results. The wound healing process of the burned skin affects not only the
      curative phase of the burned area but also result of any reconstructive procedure
      including the regional flaps. Thus, in this study, we have evaluated the wound
      healing process at the distal incisions of random-pattern skin flaps prepared
      from burned dorsal skin of rats. MATERIALS AND METHODS: Thermal burn damage was
      performed with dimensions of 3cm*3cm on Wistar albino rats. In group 1 (n=12), no
      burn was produced and 3cm*3cm caudally based, random-pattern skin flaps were
      elevated. In group 2 (n=12), a 5cm*5cm area of partial-thickness thermal damage
      was produced and after three days a 3cm*3cm random-pattern skin flap was elevated
      as in group 1 inside the burned skin site. In group 3 (n=12), 3cm*3cm area of
      partial-thickness thermal damage was produced and after three days 3cm*3cm random
      pattern skin flap was elevated. In group 4 (n=12), 3cm*3cm area of partial
      thickness thermal damage was produced and after three days a 3cm*3cm random
      pattern skin flap was elevated at the distal margin of the burned area. The flaps
      were adapted to the donor sites in all groups. The histopathological evaluation
      was done and hydroxyproline levels were measured. RESULTS: There were no
      significant differences between groups regarding presence of epithelialization,
      myofibroblast numbers, and collagen texture (p>0.05). Neovascularization level
      was significantly higher in group 2 than the other groups (p<0.05). There were no
      statistically significant difference among the hydroxyproline levels in all four
      groups (p>0.05). CONCLUSION: The preference of the incision site in a burn zone
      while designing a flap during the acute burn period was proposed to possess no
      difference in terms of wound healing in an animal model.

PMID- 23541159
TI  - High-speed AFM and applications to biomolecular systems.
AB  - Directly observing individual protein molecules in action at high spatiotemporal
      resolution has long been a holy grail for biological science. This is because we
      long have had to infer how proteins function from the static snapshots of their
      structures and dynamic behavior of optical makers attached to the molecules. This
      limitation has recently been removed to a large extent by the materialization of
      high-speed atomic force microscopy (HS-AFM). HS-AFM allows us to directly
      visualize the structure dynamics and dynamic processes of biological molecules in
      physiological solutions, at subsecond to sub-100-ms temporal resolution, without
      disturbing their function. In fact, dynamically acting molecules such as myosin V
      walking on an actin filament and bacteriorhodopsin in response to light are
      successfully visualized. In this review, we first describe theoretical
      considerations for the highest possible imaging rate of this new microscope, and
      then highlight recent imaging studies. Finally, the current limitation and future
      challenges to explore are described.

PMID- 23541161
TI  - Solid-state NMR of nanomachines involved in photosynthetic energy conversion.
AB  - Magic-angle spinning NMR, often in combination with photo-CIDNP, is applied to
      determine how photosynthetic antennae and reaction centers are activated in the
      ground state to perform their biological function upon excitation by light.
      Molecular modeling resolves molecular mechanisms by way of computational
      integration of NMR data with other structure-function analyses. By taking
      evolutionary historical contingency into account, a better biophysical
      understanding is achieved. Chlorophyll cofactors and proteins go through self
      assembly trajectories that are engineered during evolution and lead to highly
      homogeneous protein complexes optimized for exciton or charge transfer. Histidine
      cofactor interactions allow biological nanomachines to lower energy barriers for
      light harvesting and charge separation in photosynthetic energy conversion. In
      contrast, in primordial chlorophyll antenna aggregates, excessive heterogeneity
      is paired with much less specific characteristics, and both exciton and charge
      transfer character are encoded in the ground state.

PMID- 23541160
TI  - Mechanics of dynamin-mediated membrane fission.
AB  - In eukaryotic cells, membrane compartments are split into two by membrane
      fission. This ensures discontinuity of membrane containers and thus proper
      compartmentalization. The first proteic machinery implicated in catalyzing
      membrane fission was dynamin. Dynamin forms helical collars at the neck of
      endocytic buds. This structural feature suggested that the helix of dynamin could
      constrict in order to promote fission of the enclosed membrane. However,
      verifying this hypothesis revealed itself to be a challenge, which inspired many
      in vitro and in vivo studies. The primary goal of this review is to discuss
      recent structural and physical data from biophysical studies that have refined
      our understanding of the dynamin mechanism. In addition to the constriction
      hypothesis, other models have been proposed to explain how dynamin induces
      membrane fission. We present experimental data supporting these various models
      and assess which model is the most probable.

PMID- 23541164
TI  - Structures of, and related consequences of deprotonation on, two C(s)-symmetric
      arachno nine-vertex heteroboranes, 4,6-X2B7H9 (X = CH2; S) studied by gas
      electron diffraction/quantum chemical calculations and GIAO/NMR.
AB  - Gas-phase structure determinations have been performed for arachno-4,6-(CH2)2B7H9
      and arachno-4,6-S2B7H9 by combining quantum-chemical calculations and gas
      electron diffraction (GED) data. In addition, the monoanion derivatives of each
      of the aforementioned species have been studied using ab initio calculations. In
      all cases, comparison with experimental (11)B NMR chemical shifts have been
      achieved by calculating the appropriate NMR chemical shifts using GIAO-MP2
      methods and the IGLO-II basis set for various geometries, both experimental and
      calculated. The NMR parameters calculated for the geometry obtained from the
      SARACEN GED refinement appeared to be quite reasonable, and in general, the fit
      between theoretical and experimental delta((11)B) NMR was found to be
      consistently good for all four species investigated.

PMID- 23541163
TI  - Randomized controlled trial of mindfulness meditation for generalized anxiety
      disorder: effects on anxiety and stress reactivity.
AB  - OBJECTIVE: Mindfulness meditation has met increasing interest as a therapeutic
      strategy for anxiety disorders, but prior studies have been limited by
      methodological concerns, including a lack of an active comparison group. This is
      the first randomized, controlled trial comparing the manualized Mindfulness-Based
      Stress Reduction (MBSR) program with an active control for generalized anxiety
      disorder (GAD), a disorder characterized by chronic worry and physiologic
      hyperarousal symptoms. METHOD: Ninety-three individuals with DSM-IV-diagnosed GAD
      were randomly assigned to an 8-week group intervention with MBSR or to an
      attention control, Stress Management Education (SME), between 2009 and 2011.
      Anxiety symptoms were measured with the Hamilton Anxiety Rating Scale (HAMA;
      primary outcome measure), the Clinical Global Impressions-Severity of Illness and
      -Improvement scales (CGI-S and CGI-I), and the Beck Anxiety Inventory (BAI).
      Stress reactivity was assessed by comparing anxiety and distress during
      pretreatment and posttreatment administration of the Trier Social Stress Test
      (TSST). RESULTS: A modified intent-to-treat analysis including participants who
      completed at least 1 session of MBSR (n = 48) or SME (n = 41) showed that both
      interventions led to significant (P < .0001) reductions in HAMA scores at
      endpoint, but did not significantly differ. MBSR, however, was associated with a
      significantly greater reduction in anxiety as measured by the CGI-S, the CGI-I,
      and the BAI (all P values < .05). MBSR was also associated with greater
      reductions than SME in anxiety and distress ratings in response to the TSST
      stress challenge (P < .05) and a greater increase in positive self-statements (P
      = .004). CONCLUSIONS: These results suggest that MBSR may have a beneficial
      effect on anxiety symptoms in GAD and may also improve stress reactivity and
      coping as measured in a laboratory stress challenge. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01033851.

PMID- 23541162
TI  - Torque measurement at the single-molecule level.
AB  - Methods for exerting and measuring forces on single molecules have revolutionized
      the study of the physics of biology. However, it is often the case that
      biological processes involve rotation or torque generation, and these parameters
      have been more difficult to access experimentally. Recent advances in the single
      molecule field have led to the development of techniques that add the capability
      of torque measurement. By combining force, displacement, torque, and rotational
      data, a more comprehensive description of the mechanics of a biomolecule can be
      achieved. In this review, we highlight a number of biological processes for which
      torque plays a key mechanical role. We describe the various techniques that have
      been developed to directly probe the torque experienced by a single molecule, and
      detail a variety of measurements made to date using these new technologies. We
      conclude by discussing a number of open questions and propose systems of study
      that would be well suited for analysis with torsional measurement techniques.

PMID- 23541165
TI  - Structure-based virtual screening of MT2 melatonin receptor: influence of
      template choice and structural refinement.
AB  - Developing GPCR homology models for structure-based virtual screening requires
      the choice of a suitable template and refinement of binding site residues. We
      explored this systematically for the MT2 melatonin receptor, with the aim to
      build a receptor homology model that is optimized for the enrichment of active
      melatoninergic ligands. A set of 12 MT2 melatonin receptor models was built using
      different GPCR X-ray structural templates and submitted to a virtual screening
      campaign on a set of compounds composed of 29 known melatonin receptor ligands
      and 2560 drug-like decoys. To evaluate the effect of including a priori
      information in receptor models, 12 representative melatonin receptor ligands were
      placed into the MT2 receptor models in poses consistent with known mutagenesis
      data and with assessed pharmacophore models. The receptor structures were then
      adapted to the ligands by induced-fit docking. Most of the 144 ligand-adapted MT2
      receptor models showed significant improvements in screening enrichments compared
      to the unrefined homology models, with some template/refinement combinations
      giving excellent enrichment factors. The discriminating ability of the models was
      further tested on the 29 active ligands plus a set of 21 inactive or low-affinity
      compounds from the same chemical classes. Rotameric states of side chains for
      some residues, presumed to be involved in the binding process, were correlated
      with screening effectiveness, suggesting the existence of specific receptor
      conformations able to recognize active compounds. The top MT2 receptor model was
      able to identify 24 of 29 active ligands among the first 2% of the screened
      database. This work provides insights into the use of refined GPCR homology
      models for virtual screening.

PMID- 23541166
TI  - Need fulfillment in polyamorous relationships.
AB  - Polyamory is characterized by simultaneous consensual romantic relationships with
      multiple partners. Polyamory allows individuals to fulfill their relationship
      needs with multiple romantic partners, yet researchers have not identified how
      having needs met in one romantic relationship may be related to relationship
      outcomes in a concurrent relationship. Polyamorous individuals (N=1,093)
      completed online measures of need fulfillment, relationship satisfaction, and
      commitment for two concurrent romantic relationships. Participants reported high
      levels of need fulfillment and satisfaction in both relationships. Need
      fulfillment with one partner negatively predicted approximately 1% of the
      variance in relationship satisfaction with the other partner; however, there was
      no association between need fulfillment with one partner and commitment to the
      other. Generally, the findings suggest that polyamorous relationships are
      relatively independent of one another. This study provides initial evidence that
      polyamory may be a viable and fulfilling alternative way of conducting intimate
      relationships. 

PMID- 23541167
TI  - Decreased stroke volume-brachial pulse pressure ratio in patients with type 2
      diabetes over 50 years: the role of peripheral neuropathy.
AB  - BACKGROUND AND AIMS: To document the stroke volume to pulse pressure ratio
      (SV/PP, an index of total arterial compliance) and its correlates in patients
      with type 2 diabetes (T2DM) aged over 50 years whose peripheral neuropathy and
      silent myocardial ischemic (SMI) status were known. METHODS AND RESULTS: A total
      of 360 patients with T2DM aged >= 50 years, without cardiac history or symptom,
      left ventricular systolic dysfunction, dilatation and hypokinesia, were
      retrospectively enrolled. The SV/PP was calculated from echocardiographic left
      ventricular measurements and brachial blood pressure at rest. Peripheral
      neuropathy was defined as the presence of any two or more of the following:
      neuropathic symptoms, decreased distal sensation, or decreased or absent ankle
      reflexes. SMI was defined as an abnormal stress myocardial scintigraphy and/or
      stress echocardiography. A low SV/PP ratio (<0.53 ml/m2/mmHg, first tertile) was
      associated with age, creatinine clearance, 24 h urinary albumin excretion rate,
      peripheral neuropathy, hypertension, serum total cholesterol and triglycerides
      levels (p < 0.05-0.0001). In multivariate analysis, age (OR 1.1 [1.0-1.2], p <
      0.01), triglycerides (OR 1.5 [1.2-2.0], p = 0.01) and peripheral neuropathy (OR
      2.2 [1.2-3.9], p = 0.009) were independently associated with a low SV/PP. The
      patients with peripheral neuropathy had lower SV (p < 0.01) and higher PP (p <
      0.05) than those without, and only lower SV after adjustment for age and
      nephropathy. Similar results were obtained in the patients with and without SMI.
      CONCLUSION: Peripheral neuropathy was independently associated with decreased
      SV/PP, mainly through decreased SV, in patients with T2DM over 50 years.

PMID- 23541168
TI  - GATA4: the missing link between Epo and cardioprotection?!

PMID- 23541169
TI  - Diurnal eating rhythms: association with long-term development of diabetes in the
      1946 British birth cohort.
AB  - BACKGROUND AND AIMS: Few studies have described the association between time-of
      day of macronutrient intake and diabetes. This study examined the prospective
      association between time-of-day and nutrient composition of eating occasions in
      relation to diabetes incidence in the 1946 British birth cohort. METHODS AND
      RESULTS: The study included 1618 survey members who completed dietary assessment
      at age 43 (1989) and for whom data on glycosylated haemoglobin at age 53 years
      (1999) were available. Diet was assessed using 5d estimated diaries, divided into
      seven meal slots: breakfast, mid-morning, lunch, mid-afternoon, dinner, late
      evening and extras. Diabetes was defined by glycosylated haemoglobin (HbA1c) >=
      6.5% or diabetes medication use. The association between time-of-day of
      macronutrient intake at age 43 years and diabetes at age 53 years was assessed
      using logistic multivariate nutrient density models after adjustment for
      potential confounders. There were 66 cases of diabetes at age 53 years. Survey
      members with diabetes obtained 50.4% of their energy from carbohydrate at
      breakfast compared to 55.9% in survey members without diabetes (P = 0.001).
      Increasing carbohydrate intake at breakfast at the expense of fat was related to
      lower odds ratio (OR) of diabetes (OR = 0.86; 95%CI = 0.79-0.93; P < 0.001). This
      relationship was attenuated after adjustment for body mass index and waist
      circumference. CONCLUSION: Increasing energy intake from carbohydrate at the
      expense of fat at breakfast is inversely associated with 10-year diabetes
      incidence. However, further studies are required to elucidate whether the type or
      source of carbohydrates or fat influences the above association.

PMID- 23541170
TI  - Oxidative status in nondiabetic middle-aged subjects with metabolic syndrome:
      preliminary data.

PMID- 23541172
TI  - Expanding the role of percutaneous coronary intervention in patients resuscitated
      from cardiac arrest.
AB  - Special attention to post-cardiac arrest management is important to long-term
      survival and favorable neurological outcome in patients resuscitated from cardiac
      arrest. The use of emergent percutaneous coronary intervention in resuscitated
      patients presenting with ST-segment elevation myocardial infarction has long been
      considered an appropriate approach for coronary revascularization. Recent
      evidence suggests that other subsets of patients, namely, post-cardiac arrest
      patients without ST-segment elevation myocardial infarction, may benefit from
      immediate percutaneous coronary intervention following resuscitation. These
      findings could eventually have important implications for the care of
      resuscitated patients, including transportation of resuscitated patients to
      appropriate cardiac interventional facilities, access to treatment modalities
      such as therapeutic hypothermia, and coordinated care with cardiac
      catheterization laboratories.

PMID- 23541171
TI  - Protein disulfide isomerase as an antithrombotic target.
AB  - Protein disulfide isomerase (PDI) is a ubiquitously expressed oxidoreductase
      required for proper protein folding. It is highly concentrated in the endoplasmic
      reticulum, but can also be released into the extracellular environment. Several
      in vivo thrombosis models have demonstrated that vascular PDI secreted by
      platelets and endothelial cells is essential for normal thrombus formation.
      Inhibition of extracellular PDI thus represents a potential strategy for
      antithrombotic therapy. Yet this approach requires the discovery of well
      tolerated PDI inhibitors. A recent high-throughput screening identified the
      commonly ingested flavonoid, quercetin-3-rutinoside, as an inhibitor of PDI.
      Quercetin-3-rutinoside blocked thrombus formation at concentrations that are
      commonly ingested as nutritional supplements. The observation that a compound
      with Generally Recognized As Safe status inhibits PDI and blocks thrombosis in
      animal models forms a rationale for clinical trials evaluating PDI inhibitors as
      a new class of antithrombotics. 

PMID- 23541173
TI  - A culture-specific nutrient intake assessment instrument in patients with
      pulmonary tuberculosis.
AB  - BACKGROUND & AIM: To develop and evaluate a culture-specific nutrient intake
      assessment tool for use in adults with pulmonary tuberculosis (TB) in Tbilisi,
      Georgia. METHODS: We developed an instrument to measure food intake over 3
      consecutive days using a questionnaire format. The tool was then compared to 24 h
      food recalls. Food intake data from 31 subjects with TB were analyzed using the
      Nutrient Database System for Research (NDS-R) dietary analysis program. Paired t
      tests, Pearson correlations and intraclass correlation coefficients (ICC) were
      used to assess the agreement between the two methods of dietary intake for
      calculated nutrient intakes. RESULTS: The Pearson correlation coefficient for
      mean daily caloric intake between the 2 methods was 0.37 (P = 0.04) with a mean
      difference of 171 kcals/day (p = 0.34). The ICC was 0.38 (95% CI: 0.03-0.64)
      suggesting the within-patient variability may be larger than between-patient
      variability. Results for mean daily intake of total fat, total carbohydrate,
      total protein, retinol, vitamins D and E, thiamine, calcium, sodium, iron,
      selenium, copper, and zinc between the two assessment methods were also similar.
      CONCLUSIONS: This novel nutrient intake assessment tool provided quantitative
      nutrient intake data from TB patients. These pilot data can inform larger studies
      in similar populations.

PMID- 23541174
TI  - The Advanced Trauma Operative Management course--a two student to one faculty
      model.
AB  - BACKGROUND: The internationally recognized Advanced Trauma Operative Management
      (ATOM) course uses a 1:1 student-to-faculty teaching model. This study examines a
      two student to one faculty ATOM teaching model. MATERIALS AND METHODS: We
      randomly assigned 16 residents to four experienced ATOM faculty members. Half
      started with the one-student model and the other half with the two-student model
      and then switched using the same faculty. Students and faculty completed forms on
      the educational value of the two models (1 = very poor; 2 = poor; 3 = average; 4
      = good; and 5 = excellent) and identified educational preferences and
      recommendations. RESULTS: We assigned educational values for the 13 procedures as
      follows: All faculty rated the one-student model as excellent; six members rated
      the two-student model as excellent, and seven as good. Students rated 50%-75% as
      excellent and 12%-44% as good for the two-student model, and 56%-81% as excellent
      and 12%-44% as good for the one-student model. Given resource constraints, all
      faculty and 88% of students preferred the two-student model. With no resource
      constraints, 75% of students and 50% of faculty chose the two-student model. All
      faculty and students rated both models "acceptable." Overall, 81% of students and
      50% of faculty rated the two-student model better. All faculty members
      recommended that the models be optional; 94% of students recommended that they be
      either optional (50%) or a two-student model (44%). Performing or assisting on
      each procedure twice was considered an advantage of the two-student model.
      CONCLUSIONS: The two-student teaching model was acceptable and generally
      preferred in this study. With appropriately trained faculty and students, the two
      student model is feasible and should result in less animal usage and possibly
      wider promulgation.

PMID- 23541175
TI  - Use of Postural Reconstruction(r) physiotherapy to treat an adolescent with
      asymmetric bilateral genu varum and idiopathic scoliosis.
AB  - OBJECTIVE: To document the effect of Postural Reconstruction(r) physiotherapy on
      two postural disorders commonly observed in adolescents: genu varum and
      idiopathic scoliosis. PATIENT AND METHODS: A case report on a 16-year-old boy
      suffering from knee pain and presenting with bilateral genu varum and mild
      scoliosis. At the initial evaluation (T0), the intercondylar space was 7 cm and
      the Cobb angles for the right lumbar curve and left thoracic curve were 18
      degrees  and 13 degrees , respectively. The boy was treated with Postural
      Reconstruction((r)), a neuromuscular physiotherapy intervention using
      facilitation/inhibition techniques. The outcomes used to quantify the effect of 6
      months (T1), 12 months (T2) and 26 months (T3) of treatment were pain levels, the
      intercondylar space, the lumbar gibbosity and the lumbar and thoracic Cobb
      angles. RESULTS: The knee pain disappeared rapidly. At T3, the intercondylar
      space had decreased by 4 cm, the lumbar gibbosity angle had decreased by 2
      degrees  and the lumbar and thoracic Cobb angles had decreased by 8 degrees  and
      7 degrees , respectively. CONCLUSION: This non-invasive physiotherapy
      intervention appears to have considerable promise for the long-term correction of
      postural disorders.

PMID- 23541176
TI  - Copper-mediated transformation of organosilanes to nitriles with DMF and ammonium
      iodide.
AB  - Cyanation of aryl-, diaryldimethyl-, and styrylsilanes was developed for the
      first time under copper-mediated oxidative conditions using ammonium iodide and
      DMF as the combined source of nitrogen and carbon atom of the introduced cyano
      unit, respectively. The reaction was observed to proceed in a two-step process:
      initial conversion of organosilanes to their iodo intermediates and then
      cyanation. This method has a broad substrate scope with high functional group
      tolerance.

PMID- 23541177
TI  - Pyrosequencing for the rapid detection of rifampicin resistance in Mycobacterium
      tuberculosis: a meta-analysis.
AB  - BACKGROUND: Multidrug-resistant tuberculosis is a major threat to the control of
      tuberculosis and to public health. Whereas most conventional methods of drug
      susceptibility testing (DST) are precise but time consuming, pyrosequencing is a
      rapid, high-throughput technique. OBJECTIVE: To conduct a meta-analysis to
      evaluate the overall accuracy of pyrosequencing for the detection of rifampicin
      (RMP) resistance. METHODS: We searched PubMed, Web of Science, Elsevier and
      BIOSIS databases according to a written protocol and explicit study selection
      criteria. A summary receiver operating characteristic curve (SROC) and Cochrane
      (Q*) index were calculated to perform this meta-analysis using Meta-Disc
      software. RESULTS: Twelve studies involving 594 specimens with RMP resistance and
      793 RMP-susceptible specimens met the inclusion criteria. Of these, 11 were based
      on Mycobacterium tuberculosis clinical isolates. The overall sensitivity and
      specificity were estimated at respectively 0.94 (95%CI 0.92-0.96) and 0.98 (95%CI
      0.97-0.99). The area under the SROC curve was 0.99 and the Cochrane (Q*) index
      was 0.96. For clinical specimens, the overall sensitivity and specificity
      estimates were respectively 0.89 (range 0.52-1.00) and 0.99 (range 0.95-1.00).
      CONCLUSIONS: This meta-analysis shows that pyrosequencing is a highly sensitive
      and specific tool for the detection of RMP resistance in M. tuberculosis. The
      pyrosequencing assay is conducted in a high-throughput format, with a turnaround
      time of <2 h, making it substantially faster than conventional DST methods. We
      propose that pyrosequencing applied directly to clinical specimens instead of M.
      tuberculosis isolates could be of greater clinical value.

PMID- 23541178
TI  - New faunal stable carbon isotope data from the Haasgat HGD assemblage, South
      Africa, including the first reported values for Papio angusticeps and
      Cercopithecoides haasgati.

PMID- 23541179
TI  - Cosmogenic 26Al/10Be burial dating of the Paleolithic at Xihoudu, North China.

PMID- 23541180
TI  - Bilateral traumatic facial paralysis. Case report.
AB  - Although traumatic injury of the facial nerve is a relatively common condition in
      neurosurgical practice, bilateral lesions related to fracture of temporal bones
      are seldom seen. We report the case of a 38-year-old patient admitted to
      Intensive Care Unit after severe head trauma requiring ventilatory support
      (Glasgow Coma Scale of 7 on admission). A computed tomography (CT) scan confirmed
      a longitudinal fracture of the right temporal bone and a transversal fracture of
      the left. After successful weaning from respirator, bilateral facial paralysis
      was observed. The possible aetiologies for facial diplegia differ from those of
      unilateral injury. Due to the lack of facial asymmetry, it can be easily missed
      in critically ill patients, and both the high resolution CT scan and
      electromyographic studies can be helpful for correct diagnosis. 

PMID- 23541181
TI  - Mechanistic insight on the Diels-Alder reaction catalyzed by a self-assembled
      molecular capsule.
AB  - We combined Monte Carlo simulations and density functional theory calculations to
      study the mechanism of the Diels-Alder reaction of p-quinone and cyclohexadiene
      catalyzed by a self-assembled molecular capsule. Our calculations show that the
      encapsulation of the reactants into the cage is driven by hydrogen-bonding
      interactions and pi-pi stacking interactions between two reactants and the
      capsule. The encapsulated Diels-Alder reaction at different locations inside the
      capsule may have quite different reactivity due to different guest-host
      interactions. A comparison of the free energy profiles of the Diels-Alder
      reaction in the capsule and in the bulk solution reveals that the Diels-Alder
      reaction in the capsule is accelerated because the host-guest interaction leads
      to a relatively smaller barrier for the cycloaddition step.

PMID- 23541182
TI  - Sensitive GC-MS/MS method to measure deuterium labeled deoxyadenosine in DNA from
      limited mouse cell populations.
AB  - A rapid and sensitive gas chromatography-tandem mass spectrometry (GC-MS/MS)
      method was developed to quantitatively measure low levels of DNA base
      deoxyadenosine (dA) and its isotopologues (e.g., dA M+1) from limited mouse cell
      populations. Mice undergoing allogeneic hematopoietic transplantation (AHSCT)
      received deuterated water at biologically relevant time intervals post AHSCT,
      allowing labeling of DNA upon cell division, which was detected as the dA M+1
      isotopologue. Targeted mouse cell populations were isolated from lymphoid organs
      and purified by multiparameter fluorescence activated cell sorting. Cell lysis,
      DNA extraction, and hydrolysis were accomplished using available commercial
      procedures. The novel analytical method utilized a hydrophilic-lipophilic
      balanced sample preparation, rapid online hot GC inlet gas phase sample
      derivatization, fast GC low thermal mass technology, and a recently marketed GC
      MS/MS system. Calibration standards containing dA and fortified with relevant
      levels of dA M+1 (0.25-20%) and dA M+5 (internal standard) were used for sample
      quantitation. The method employed a quadratic fit for calibration of dA M+1 (0.25
      20%) and dA, demonstrated excellent accuracy and precision, and had limits of
      detection of 100 fg on-column for the dA isotopologues. The method was validated
      and required only 20 000 cells to characterize population dynamics of cells
      involved in the biology of chronic graft-versus-host disease, the main cause of
      late morbidity and nonrelapse-mortality following AHSCT. The high sensitivity and
      specificity of the method makes it useful for investigating in vivo kinetics on
      limited and important cell populations (e.g., T regulatory cells) from disease
      conditions or in disease models that are immune-mediated, such as diabetes, human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), arthritis,
      inflammatory bowel disease, and multiple sclerosis. 

PMID- 23541183
TI  - Various approaches for vascular health in elderly women.
AB  - Cardiovascular disease is one of the leading causes of morbidity and mortality in
      elderly women. Several previous studies evaluated various cardiovascular risk
      factors, such as brachial blood pressure (BP), systolic blood pressure (SBP),
      pulse pressure (PP), pulse wave velocity (PWV), central aortic pressure (CAP),
      and so on. More recently, measurement of ambulatory blood pressure (AMBP) was
      shown to be superior to clinic measurements in predicting cardiovascular
      mortality. However, the data are limited concerning the relationship among these
      variables in elderly women. In the present study, the data for clinic BP
      including PP, PWV, CAP, and AMSBP and AMCAP obtained using BPro were evaluated in
      24 elderly hypertensive women. Although there was a significant correlation
      between AMSBP and AMCAP, no correlations were found between repeated measured
      values and values measured in the clinic on one occasion. In conclusion,
      measuring PWV and CAP in the clinic in patients with white coat hypertension or
      masked hypertension may not be an accurate way to measure these parameters.

PMID- 23541185
TI  - Hippocampal sulcal cavities in depression and healthy individuals.
AB  - BACKGROUND: A literature review suggested age and cognitive problems to be
      related to an increased prevalence of small areas of signal variation within the
      hippocampus observed on MRI, described as hippocampal sulcal cavities (HSCs;
      (Maller et al., 2011)). The current study aimed to describe the prevalence of
      HSCs in patients with treatment-resistant depression (TRD) and healthy controls
      over a large age-range. METHODS: 115 TRD patients and 86 controls underwent MRI
      brain scanning. Right and left HSCs were rated separately for prevalence and
      length. RESULTS: HSCs were observed in 73.04% of those with TRD, statistically
      more prevalent (p=0.001) than amongst controls (51.16%). These findings are
      consistent with our review (66% prevalence in memory disorders and 47% in healthy
      controls). Furthermore, HSC presence and length was associated with aging.
      LIMITATIONS: The study was cross-sectional so its implications for aging are
      tentative. A larger sample scanned longitudinally will allow for more
      sophisticated statistical methods by which to investigate the relationship
      between HSCs, aging, and TRD. CONCLUSIONS: Although their clinical significance
      remains uncertain, the results of the current study suggest that HSCs are related
      with age and those with TRD have more aged brains than their peers.

PMID- 23541186
TI  - Integration of alkyl-substituted bipyridyl benzenedithiolato platinum(II)
      complexes with cadmium(II) ion via selective dative bond formation.
AB  - The presence of lone pairs on the Pt and S atoms of [Pt(Bdt)(DTBbpy)] (1) (Bdt =
      1,2-benzenedithiolato and DTBbpy = 4,4'-di-tert-butyl-2,2'-bipyridine) and
      [Pt(Bdt)(C13bpy)] (2) (C13bpy = 4,4'-ditridecyl-2,2'-bipyridine) led to selective
      dative bond formation with Cd(II). Complexes 1 and 2 show no binding interaction
      with Zn(II), while they bind selectively with Cd(II) to give a twisted trinuclear
      complex, [Cd{Pt(Bdt)(DTBbpy)}2(ClO4)(H2O)](ClO4) (3), and a shuttlecock-shaped
      tetranuclear complex, [Cd{Pt(Bdt)(C13bpy)}3(H2O)](ClO4)2.CH2Cl2 (4),
      respectively, depending upon the alkyl groups substituted on the 2,2'-bipyridine.
      The two platinum moieties in 3 are connected to the seven-coordinated Cd atom
      through Pt -> Cd (2.7331(7) and 2.7936(7) A) and S -> Cd (2.690(3), 2.940(3), and
      3.067(3) A) dative bonds, while the three moieties in 4 are connected to the
      tetrahedral Cd atom only by S -> Cd (2.552(4) A) dative bonds. These structural
      variations found in 3 and 4 are caused not only by steric hindrance of the t-Bu
      groups but also by the microsegregation effect derived from the tridecyl chains.
      The three platinum moieties in 4 align so as to form a parallel orientation of
      their dipole moments, in contrast to the twisted arrangement found in 3. The
      dative bonds formed in 3 and 4 are commonly stable in the solid state and in less
      coordinative solvents such as dichloromethane, while dissociation behavior of
      platinum moieties with Cd(II) was observed in more coordinative THF. UV-vis and
      NMR spectroscopy unsealed the characteristic association/dissociation properties
      depending on the coordination abilities of solvents. Finally, the present study
      revealed that the formation of dative bonds between the platinum moieties with
      Cd(II) plays important roles not only in stabilizing the ground states, which
      leads to blue shifts in both absorption and emission energies, but also in
      electronic interactions between the moieties, which are revealed by
      electrochemical studies.

PMID- 23541187
TI  - Association of plasma and cortical amyloid beta is modulated by APOE epsilon4
      status.
AB  - BACKGROUND: Apolipoprotein E (APOE) epsilon4 allele's role as a modulator of the
      relationship between soluble plasma amyloid beta (Abeta) and fibrillar brain
      Abeta measured by Pittsburgh compound B positron emission tomography ([(11)C]PiB
      PET) has not been assessed. METHODS: Ninety-six Alzheimer's Disease Neuroimaging
      Initiative participants with [(11)C]PiB scans and plasma Abeta1-40 and Abeta1-42
      measurements at the time of PET scanning were included. Regional and voxelwise
      analyses of [(11)C]PiB data were used to determine the influence of APOE epsilon4
      allele on association of plasma Abeta1-40, Abeta1-42, and Abeta1-40/Abeta1-42
      with [(11)C]PiB uptake. RESULTS: In APOE epsilon4- but not epsilon4+
      participants, positive relationships between plasma Abeta1-40/Abeta1-42 and
      [(11)C]PiB uptake were observed. Modeling the interaction of APOE and plasma
      Abeta1-40/Abeta1-42 improved the explained variance in [(11)C]PiB binding
      compared with using APOE and plasma Abeta1-40/Abeta1-42 as separate terms.
      CONCLUSIONS: The results suggest that plasma Abeta is a potential Alzheimer's
      disease biomarker and highlight the importance of genetic variation in
      interpretation of plasma Abeta levels.

PMID- 23541188
TI  - The neuropsychology of normal aging and preclinical Alzheimer's disease.
AB  - OBJECTIVE: A National Institute on Aging-sponsored work group on preclinical
      Alzheimer's disease (AD) articulated the need to characterize cognitive
      differences between normal aging and preclinical AD. METHODS: Seventy-one
      apolipoprotein E (APOE) epsilon4 homozygotes, 194 epsilon3/epsilon4
      heterozygotes, and 356 epsilon4 noncarriers age 21 to 87 years who were
      cognitively healthy underwent neuropsychological testing every 2 years.
      Longitudinal trajectories of test scores were compared between APOE subgroups.
      RESULTS: There was a significant effect of age on all cognitive domains in both
      APOE epsilon4 carriers and noncarriers. A significant effect of APOE epsilon4
      gene dose was confined to the memory domain and the Dementia Rating Scale. Cross
      sectional comparisons did not discriminate the groups. CONCLUSIONS: Although
      cognitive aging patterns are similar in APOE epsilon4 carriers and noncarriers,
      preclinical AD is characterized by a significant epsilon4 gene dose effect that
      impacts memory and is detectable longitudinally. Preclinical neuropsychological
      testing strategies should emphasize memory-sensitive measures and longitudinal
      design.

PMID- 23541189
TI  - Effectiveness of lurasidone for patients with schizophrenia following 6 weeks of
      acute treatment with lurasidone, olanzapine, or placebo: a 6-month, open-label,
      extension study.
AB  - OBJECTIVE: The primary objective was to evaluate the safety and tolerability of
      lurasidone, a new atypical antipsychotic agent, in the longer-term treatment of
      schizophrenia (DSM-IV). Persistence of symptom improvement was assessed as a
      secondary outcome. METHOD: Patients who completed a 6-week, double-blind, placebo
      controlled study evaluating the efficacy of fixed doses of once-daily lurasidone
      (40 or 120 mg) or olanzapine 15 mg (to confirm assay sensitivity) were eligible
      to receive flexibly dosed lurasidone 40 to 120 mg/d in this 6-month, open-label
      extension study (conducted from March 2008 to December 2009). Assessments of
      safety and tolerability were conducted at open-label baseline, at day 10, and
      monthly thereafter. RESULTS: Of 254 enrolled patients, 113 (44.5%) completed 6
      months of open-label treatment. During the open-label study (month 6 observed
      cases), small decreases were observed in mean weight (-0.1 kg) and median lipid
      levels (total cholesterol, -6.5 mg/dL; low-density lipoprotein, 0.0 mg/dL; high
      density lipoprotein, 0.0 mg/dL; triglycerides, -8.5 mg/dL). Patients previously
      treated with olanzapine (n = 69) experienced decrease in weight and improvement
      in lipid levels, whereas patients previously treated with lurasidone (n = 115) or
      placebo (n = 62) experienced minimal changes. No clinically meaningful changes
      were observed in median prolactin levels. The 2 most commonly reported adverse
      events were akathisia (13.0%) and insomnia (11.0%). Persistent antipsychotic
      efficacy of lurasidone was shown for patients who had previously received
      lurasidone, olanzapine, or placebo; further reductions from open-label baseline
      to final visit were observed in mean PANSS total score (-8.7) for all patients.
      CONCLUSIONS: Open-label treatment with flexibly dosed lurasidone (40-120 mg/d)
      was generally safe, well tolerated, and effective over a 6-month period in
      patients who had completed a preceding 6-week, double-blind study.

PMID- 23541190
TI  - Prevalence, serotype diversity, and antimicrobial resistance of Salmonella in
      imported shipments of spice offered for entry to the United States, FY2007
      FY2009.
AB  - In response to increased concerns about spice safety, the U.S. FDA initiated
      research to characterize the prevalence of Salmonella in imported spices.
      Shipments of imported spices offered for entry to the United Sates were sampled
      during the fiscal years 2007-2009. The mean shipment prevalence for Salmonella
      was 0.066 (95% CI 0.057-0.076). A wide diversity of Salmonella serotypes was
      isolated from spices; no single serotype constituted more than 7% of the
      isolates. A small percentage of spice shipments were contaminated with
      antimicrobial-resistant Salmonella strains (8.3%). Trends in shipment prevalence
      for Salmonella associated with spice properties, extent of processing, and export
      country, were examined. A larger proportion of shipments of spices derived from
      fruit/seeds or leaves of plants were contaminated than those derived from the
      bark/flower of spice plants. Salmonella prevalence was larger for shipments of
      ground/cracked capsicum and coriander than for shipments of their whole spice
      counterparts. No difference in prevalence was observed between shipments of spice
      blends and non-blended spices. Some shipments reported to have been subjected to
      a pathogen reduction treatment prior to being offered for U.S. entry were found
      contaminated. Statistical differences in Salmonella shipment prevalence were also
      identified on the basis of export country.

PMID- 23541191
TI  - Predominant enterobacteria on modified-atmosphere packaged meat and poultry.
AB  - Enterobacteria on modified-atmosphere (MA) packaged meat (n = 54) and poultry (n
      = 32) products were enumerated, and 899 isolates were picked and ribotyped. For
      identification, 16S rRNA genes of representative strains were sequenced and
      analyzed. Altogether 54 (60%) of the samples contained enterobacteria >10(4)
      CFU/g. In 34% of the poultry samples, enterobacteria counts were >10(6) CFU/g
      suggesting that enterobacteria may contribute to spoilage of MA packaged poultry.
      The enterobacteria identified were predominantly Hafnia spp. (40%) and Serratia
      spp. (42%) with Hafnia alvei, Hafnia paralvei, Serratia fonticola, Serratia
      grimesii, Serratia liquefaciens, Serratia proteamaculans, and Serratia
      quinivorans being the species identified. In addition, 6% of the isolates were
      identified as Rahnella spp., 3% as Yersinia spp., and 1% as Buttiauxella spp.
      Percentage distributions of the predominant genera in different products showed
      that 89% of the Serratia spp. were from products packaged under a high-O2 MA
      containing CO2 (25-35%), whereas most (76%) isolates of Hafnia originated from
      anaerobically packaged red meat and poultry. These findings suggest that the gas
      mixture used for MA packaging influence the selection of enterobacteria growing
      on meat and poultry.

PMID- 23541192
TI  - Evaluation of the strain variability of Salmonella enterica acid and heat
      resistance.
AB  - The inherent acid and heat resistances of 60 Salmonella enterica strains were
      assessed in tryptone soy broth without dextrose acidified to pH 3.0 or heated at
      57  degrees C. A total of 360 inactivation curves were generated. Regarding the
      acid challenge experiments, the inactivation rate (kacid), estimated using the
      log-linear model, ranged from 0.47 to 3.25 h(-1). A log-linear model with a
      "survival tail" was used to describe the thermal inactivation of the strains, and
      the estimated inactivation rate (kheat) ranged from 0.42 to 1.33 min(-1). The
      strain variability of kacid was considerably higher than that of kheat with the
      coefficient of variation of this kinetic parameter among the tested strains being
      39.0% and 18.3%, respectively. No correlation was observed between the estimated
      kacid and kheat values of the 60 S. enterica strains. Furthermore, no trends
      among the tested strains related to origin, serotype or antibiotic resistance
      profile were evident. The present study is the first one to comparatively
      evaluate the inherent acid and heat resistance profiles of multiple S. enterica
      strains. Beyond their value in strain selection for use in food safety challenge
      studies, the collected data should be useful in describing and integrating the
      strain variability of S. enterica acid and heat resistance profiles in
      quantitative microbial risk assessment.

PMID- 23541193
TI  - Novel touchdown-PCR method for the detection of putrescine producing gram
      negative bacteria in food products.
AB  - Formation of biogenic amines may occur in food due to metabolic activities of
      contaminating Gram-negative bacteria. Putrescine is assumed to be the major
      biogenic amine associated with microbial food spoilage. Gram-negative bacteria
      can form putrescine by three metabolic pathways that can include eight different
      enzymes. The objective of this study was to design new sets of primers able to
      detect all important enzymes involved in the production of putrescine by Gram
      negative bacteria. Seven new sets of consensual primers based on gene sequences
      of different bacteria were designed and used for detection of the speA, adiA,
      adi, speB, aguA, speC, and speF genes. A newly developed touchdown polymerase
      chain reaction (PCR) method using these primers was successfully applied on
      several putrescine-producers. Selected PCR products were sequenced and high
      similarity of their sequences (99-91%) with known sequences of the corresponding
      genes confirmed high specificity of the developed sets of primers. Furthermore,
      all the investigated bacteria produced both putrescine and agmatine, an
      intermediate of putrescine production, which was confirmed by chemical analysis.
      The developed new touchdown PCR method could easily be used to detect potential
      foodborne Gram-negative producers of putrescine. The newly developed sets of
      primers could also be useful in further research on putrescine metabolism in
      contaminating microbiota.

PMID- 23541194
TI  - Taxonomic and molecular characterization of lactic acid bacteria and yeasts in
      nunu, a Ghanaian fermented milk product.
AB  - Produced from raw unpasteurized milk, nunu is a spontaneously fermented yoghurt
      like product made in Ghana and other parts of West Africa. Despite the importance
      of nunu in the diet of many Africans, there is currently only limited information
      available on the microorganisms associated with nunu processing. With the aim of
      obtaining a deeper understanding of the process and as a first step towards
      developing starter cultures with desired technological properties for nunu
      production, a microbiological characterization of nunu processing in three
      different towns in the Upper East region of Ghana, namely Bolgatanga, Paga and
      Navrongo, was carried out. Lactic acid bacteria (LAB) and yeasts associated with
      nunu processing were isolated and identified using a combination of pheno- and
      genotypic methods including morphological and carbohydrate fermentation tests,
      (GTG)5-based rep-PCR, multiplex PCR, and 16S and 26S rRNA gene sequencing. The
      LAB counts during nunu processing increased from 4.5 +/- 0.4 log cfu/ml at 0 h to
      8.7 +/- 1.8 log cfu/ml at 24 h of fermentation while yeasts counts increased from
      2.8 +/- 1.2 log cfu/ml at 0 h to 5.8 +/- 0.5 log cfu/ml by the end of
      fermentation. Lactobacillus fermentum was the dominant LAB throughout the
      fermentations with Lactobacillus plantarum and Leuconostoc mesenteroides playing
      prominent roles during the first 6-8 h of fermentation as well. Less frequently
      isolated LAB included Lactobacillus helveticus, Enterococcus faecium,
      Enterococcus italicus, Weissella confusa and a putatively novel Lactococcus spp.
      The yeasts involved were identified as Candida parapsilosis, Candida rugosa,
      Candida tropicalis, Galactomyces geotrichum, Pichia kudriavzevii and
      Saccharomyces cerevisiae with P. kudriavzevii and S. cerevisiae being the
      dominant yeast species.

PMID- 23541195
TI  - Effect of natural microbiota on growth of Salmonella spp. in fresh pork--a
      predictive microbiology approach.
AB  - This study was undertaken to model and predict growth of Salmonella and the
      dominating natural microbiota, and their interaction in ground pork. Growth of
      Salmonella in sterile ground pork at constant temperatures between 4  degrees C
      and 38  degrees C was quantified and used for developing predictive models for
      lag time, max. specific growth rate and max. population density. Data from
      literature were used to develop growth models for the natural pork microbiota.
      Challenge tests at temperatures from 9.4 to 24.1  degrees C and with Salmonella
      inoculated in ground pork were used for evaluation of interaction models. The
      existing Jameson-effect and Lotka-Volterra species interaction models and a new
      expanded Jameson-effect model were evaluated. F-test indicated lack-of-fit for
      the classical Jameson-effect model at all of the tested temperatures and at 14.1
      20.2  degrees C this was caused by continued growth of Salmonella after the
      natural microbiota had reached their max. population density. The new expanded
      Jameson-effect model and the Lotka-Volterra model performed better and
      appropriately described the continued but reduced growth of Salmonella after the
      natural microbiota had reached their max. population density. The expanded
      Jameson-effect model is a new and simple species interaction model, which
      performed as well as the more complex Lotka-Volterra model.

PMID- 23541196
TI  - The application of high-concentration short-time chlorine dioxide treatment for
      selected specialty crops including Roma tomatoes (Lycopersicon esculentum),
      cantaloupes (Cucumis melo ssp. melo var. cantaloupensis) and strawberries
      (Fragaria*ananassa).
AB  - The effects of high-concentration short-time chlorine dioxide (ClO2) gas
      treatment on food-borne pathogens inoculated onto the surface of tomatoes,
      cantaloupes, and strawberries were studied. Produce were spot-inoculated with a
      mixture of Salmonella enterica (serotypes Montevideo, Javiana and Baildon),
      Escherichia coli O157:H7 (serotypes 204 P, EDL 933 and C792) or Listeria
      monocytogenes (serotypes Scott A, F 5069 and LCDC 81-861), and treated with ClO2
      gas at 10 mg/l for 180 s. After ClO2 gas treatment, surviving populations were
      determined and shelf-life studies were conducted (microbial spoilage population,
      change in color and overall appearance). Significant microbial reduction (p <
      0.05) was observed for all treated samples. Nearly a 5LogCFU/cm(2)Salmonella
      reduction was found on tomatoes, cantaloupe and strawberries, while a
      ~3LogCFU/cm(2) reduction was observed for E. coli and Listeria on all produce
      surfaces. E. coli and Listeria appeared to be more resistant to ClO2 gas as
      compared to Salmonella spp. Treatments significantly (p < 0.05) reduced initial
      microflora population, while produce color surface was not significantly
      influenced, as compared to the control (p > 0.05). Results obtained suggest the
      potential use of high-concentration short-time ClO2 gas treatment as an effective
      online pathogen inactivation technology for specialty crops in large-scale
      produce packing operations.

PMID- 23541197
TI  - The Pathogen-annotated Tracking Resource Network (PATRN) system: a web-based
      resource to aid food safety, regulatory science, and investigations of foodborne
      pathogens and disease.
AB  - Investigation of foodborne diseases requires the capture and analysis of time
      sensitive information on microbial pathogens that is derived from multiple
      analytical methods and sources. The web-based Pathogen-annotated Tracking
      Resource Network (PATRN) system (www.patrn.net) was developed to address the data
      aggregation, analysis, and communication needs important to the global food
      safety community for the investigation of foodborne disease. PATRN incorporates a
      standard vocabulary for describing isolate metadata and provides a
      representational schema for a prototypic data exchange standard using a novel
      data loading wizard for aggregation of assay and attribution information. PATRN
      currently houses expert-curated, high-quality "foundational datasets" consisting
      of published experimental results from conventional assays and next generation
      analysis platforms for isolates of Escherichia coli, Listeria monocytogenes, and
      Salmonella, Shigella, Vibrio and Cronobacter species. A suite of computational
      tools for data mining, clustering, and graphical representation is available.
      Within PATRN, the public curated data repository is complemented by a secure
      private workspace for user-driven analyses, and for sharing data among
      collaborators. To demonstrate the data curation, loading wizard features, and
      analytical capabilities of PATRN, three use-case scenarios are presented. Use
      case scenario one is a comparison of the distribution and prevalence of plasmid
      encoded virulence factor genes among 249 Cronobacter strains with similar
      attributes to that of nine Cronobacter isolates from recent cases obtained
      between March and October, 2010-2011. To highlight PATRN's data management and
      trend finding tools, analysis of datasets, stored in PATRN as part of an ongoing
      surveillance project to identify the predominant molecular serogroups among
      Cronobacter sakazakii isolates observed in the USA is shown. Use-case scenario
      two demonstrates the secure workspace available for private users to upload and
      analyze sensitive data, and for collating cross-platform datasets to identify and
      validate congruent datapoints. SNP datasets from WGS assemblies and pan-genome
      microarrays are analyzed in a combinatorial fashion to determine relatedness of
      33 Salmonella enterica strains to six strains collected as part of an outbreak
      investigation. Use-case scenario three utilizes published surveillance results
      that describe the incidence and sources of O157:H7 E. coli isolates associated
      with a produce pre-harvest surveillance study that occurred during 2002-2006. In
      summary, PATRN is a web-based integrated platform containing tools for the
      management, analysis and visualization of data about foodborne pathogens.

PMID- 23541198
TI  - Antimicrobial resistance and co-selection phenomenon in Listeria spp. recovered
      from food and food production environments.
AB  - Antimicrobial resistance (AMR), co-selection phenomenon, and the relationship
      between reduced susceptibility (RSC) to ciprofloxacin (CIP) and resistance to
      other antimicrobials in Listeria spp. (n = 103) recovered from food processing
      environments (FPE) and food were investigated. Resistance of Listeria
      monocytogenes and other listeriae, respectively, to cefoxitin (FOX; 98% vs. 88%),
      CIP (7% vs. 4%), clindamycin (CLI; 33% vs. 59%) and tetracycline (6% vs. 8%) was
      observed, as was RSC to CIP (67% vs. 57%) and CLI (65% vs. 41%). L. monocytogenes
      also possessed RSC to linezolid (LZD; 6%), rifampicin (2%) and streptomycin (6%),
      with other listeriae displaying RSC to chloramphenicol (4%). L. monocytogenes
      serotype 1/2a (90%) isolates were more frequently resistant or possessed RSC to
      CIP compared to serotype 4b (55%) (p = 0.015). When eight strains were
      experimentally adapted to high concentrations of CIP, co-selection occurred as
      MICs to benzalkonium chloride (BAC) increased (n = 5), gentamicin MICs remained
      the same (n = 6) or increased 2-fold (n = 2), and led to RSC to LZD (n = 1) and
      resistance to CLI (n = 8). Overall, levels of resistance/RSC to CIP in food chain
      isolates, particularly 1/2a, are concerning. Further, reduced sensitivity to
      disparate antimicrobials following CIP exposure highlights the need for increased
      knowledge of co-selection phenomenon linked with antimicrobial agents.

PMID- 23541199
TI  - Inactivation strategy for Clostridium perfringens spores adhered to food contact
      surfaces.
AB  - The contamination of enterotoxigenic Clostridium perfringens spores on food
      contact surfaces posses a serious concern to food industry due to their high
      resistance to various preservation methods typically applied to control foodborne
      pathogens. In this study, we aimed to develop an strategy to inactivate C.
      perfringens spores on stainless steel (SS) surfaces by inducing spore germination
      and killing of germinated spores with commonly used disinfectants. The mixture of
      l-Asparagine and KCl (AK) induced maximum spore germination for all tested C.
      perfringens food poisoning (FP) and non-foodborne (NFB) isolates. Incubation
      temperature had a major impact on C. perfringens spore germination, with 40 
      degrees C induced higher germination than room temperature (RT) (20 +/- 2 
      degrees C). In spore suspension, the implementation of AK-induced germination
      step prior to treatment with disinfectants significantly (p < 0.05) enhanced the
      inactivation of spores of FP strain SM101. However, under similar conditions, no
      significant spore inactivation was observed with NFB strain NB16. Interestingly,
      while the spores of FP isolates were able to germinate with AK upon their
      adhesion to SS chips, no significant germination was observed with spores of NFB
      isolates. Consequently, the incorporation of AK-induced germination step prior to
      decontamination of SS chips with disinfectants significantly (p < 0.05)
      inactivated the spores of FP isolates. Collectively, our current results showed
      that triggering spore germination considerably increased sporicidal activity of
      the commonly used disinfectants against C. perfringens FP spores attached to SS
      chips. These findings should help in developing an effective strategy to
      inactivate C. perfringens spores adhered to food contact surfaces.

PMID- 23541200
TI  - Microbiological examination of ready-to-eat foods and ready-to-bake frozen
      pastries from university canteens.
AB  - During a 10-year inspection survey (2001-2010), a microbiological study of ready
      to-eat (RTE) foods and ready-to-bake frozen pastries from 15 canteens of the
      university campus was undertaken to determine their microbiological quality. The
      cumulative study revealed that the aerobic colony counts for the RTE product
      groups were as follows: from 10(6) to 10(8) CFU/g for 50% of sandwiches; under
      the detection limit (<10 CFU/g) for 88.6% of oven baked pastries; <10(5) CFU/g
      for 86.5% of desserts oven baked; from 10(3) to 10(9) CFU/g for desserts with
      dairy cream. The highest mean Enterobacteriaceae counts were recorded for
      desserts with dairy cream. The highest percentages of foodborne pathogens were:
      20% Listeria monocytogenes and 12.5% Staphylococcus aureus in desserts with dairy
      cream; 17.5% Salmonella spp. and 8.5% presumptive Escherichia coli O157 in
      sandwiches; 14.6% Bacillus cereus in oven baked pastries. Aerobic colony counts
      were in the range 10(7)-10(8) CFU/g for 48.8% of frozen pastries; whereas
      Enterobacteriaceae counts between 10(3) and 10(4) CFU/g were detected in 35.3%.
      Foodborne pathogens prevalences for frozen pastries were as follows: B. cereus,
      31.8%; Salmonella spp., 28.6%; presumptive E. coli O157, 25%; S. aureus, 8.7%; L.
      monocytogenes, 8.7%. Improved sanitary conditions in the processing plants and
      precautionary measures are necessary for consumer protection.

PMID- 23541201
TI  - Genotyping of dairy Bacillus licheniformis isolates by high resolution melt
      analysis of multiple variable number tandem repeat loci.
AB  - In dairy foods, the sporeformer Bacillus licheniformis can be the cause of
      spoilage or specification compliance issues. Currently used methods for
      genotyping B. licheniformis have limited discrimination with only 2 or 3
      different subgroups being identified. Here, we have developed a multi-locus
      variable number tandem repeat analysis (MLVA) method and combined it with high
      resolution melt analysis (MLV-HRMA) for genotyping B. licheniformis. Five
      repetitive loci were identified and used as markers for genotyping 52 isolates
      from two milk powder processing plants and retail samples. Nineteen genotypes
      could be identified using both MLVA and MLV-HRMA leading to Hunter-Gaston
      discrimination indices (D-value) of 0.93 each. It was found that all 5 MLVA loci
      were stable following 10 days of sub-culturing of 8 representative isolates. All
      isolates were also genotyped using previously used methods including randomly
      amplified polymorphic DNA-PCR (RAPD) and partial rpoB sequencing. Five different
      RAPD profiles and 5 different partial rpoB sequence types were identified
      resulting in corresponding D-values of 0.6 and 0.46, respectively. Analysis of
      the genotypes from dairy samples revealed that dairy B. licheniformis isolates
      are more heterogeneous than previously thought and that this new method can
      potentially allow for more discriminatory tracking and monitoring of specific
      genotypes.

PMID- 23541202
TI  - The effect of American cranberry (Vaccinium macrocarpon) constituents on the
      growth inhibition, membrane integrity, and injury of Escherichia coli O157:H7 and
      Listeria monocytogenes in comparison to Lactobacillus rhamnosus.
AB  - The antimicrobial properties of the American cranberry were studied against
      Escherichia coli O157:H7, Listeria monocytogenes, and Lactobacillus rhamnosus to
      determine the effects on growth inhibition, membrane permeability, and injury.
      Cranberry powder was separated using a C-18 Sep-Pak cartridge into sugars plus
      organic acids (F1), monomeric phenolics (F2), and anthocyanins plus
      proanthocyanidins (F3). Fraction 3 was further separated into anthocyanins (F4)
      and proanthocyanidins (F5) using an LH-20 Sephadex column. Each fraction was
      diluted in the brain heart infusion (BHI) broth to determine the minimum
      inhibitory/bactericidal concentrations (MIC/MBC). L. monocytogenes was the most
      susceptible to cranberry fraction treatment with the lowest MIC/MBC for each
      treatment, followed by E. coli O157:H7 and L. rhamnosus. Membrane permeability
      and potential was studied using LIVE/DEAD viability assay and using Bis (1, 3
      dibutylbarbituric acid) trimethine oxonol (DiBAC4), respectively. L. rhamnosus
      demonstrated the highest permeability followed by E. coli O157:H7, and L.
      monocytogenes. L. rhamnosus demonstrated the highest recovery followed by E. coli
      O157:H7, and L. monocytogenes. Each cranberry fraction demonstrated membrane
      hyperpolarization at their native pH, while F2, F3, and F5 demonstrated membrane
      depolarization at neutral pH. With this knowledge cranberry compounds may be used
      to prevent maladies and potentially substitute for synthetic preservatives and
      antibiotics.

PMID- 23541203
TI  - Microbial succession and metabolite changes during fermentation of saeu-jeot:
      traditional Korean salted seafood.
AB  - Saeu-jeot is made by the fermentation of highly salted [approximately 25% (w/v)]
      shrimp in Korea. Saeu-jeot samples were prepared in triplicate and their cell
      number, bacterial community, and metabolites were monitored periodically for 183
      days. Quantitative PCR showed that bacterial populations were much more abundant
      than archaeal populations during the entire saeu-jeot fermentation period, which
      suggested that bacterial populations, not archaeal populations, might be
      primarily responsible for saeu-jeot fermentation. Pyrosequencing analysis
      revealed that Proteobacteria were dramatically replaced with halophilic
      Firmicutes as the fermentation progressed and members of Pseudoalteromonas,
      Staphylococcus, Salimicrobium, and Alkalibacillus were sequentially dominant and,
      eventually, Halanaerobium predominated after 66 days of fermentation. Halophilic
      archaeal genera, Halorubrum, Halolamina, Halobacterium, Haloarcula, and
      Haloplanus belonging to Euryarchaeota, were dominant, but their communities were
      relatively constant over the entire fermentation period. Metabolite analysis
      using a (1)H NMR spectroscopy showed that the amount of metabolites including
      amino acids, glycerol, and nitrogen compounds rapidly increased during the early
      fermentation stage, but their levels were relatively constant or they decreased
      after approximately 49 days of fermentation. A statistical analysis based on
      bacterial communities and metabolites demonstrated that members of Halanaerobium
      might be responsible for the production of acetate, butyrate, and methylamines
      after 66 days of fermentation, which could be considered as a potential indicator
      to decide the appropriate seafood fermentation time. This study will provide
      insights into the microbial succession and metabolites of fermented seafood and
      allow for a greater understanding of the relationships between the microbial
      community and metabolites in seafood fermentation.

PMID- 23541204
TI  - Effect of pH, salt and chemical rinses on bacterial attachment to extracellular
      matrix proteins.
AB  - Microbial contamination of carcass surfaces occurs during slaughter and post
      slaughter processing steps, therefore interventions are needed to enhance meat
      safety and quality. Although many studies have been done at the macro-level,
      little is known about specific processes that influence bacterial attachment to
      carcass surfaces, particularly the role of extracellular matrix (ECM) proteins.
      In the present study, the effect of pH and salt (NaCl, KCl and CaCl2) on
      attachment of Escherichia coli and Salmonella isolates to dominant ECM proteins:
      collagen I, fibronectin, collagen IV and laminin were assessed. Also, the effects
      of three chemical rinses commonly used in abattoirs (2% acetic acid, 2% lactic
      acid and 10% trisodium phosphate (TSP)) were tested. Within a pH range of 5-9,
      there was no significant effect on attachment to ECM proteins, whereas the effect
      of salt type and concentration varied depending on combination of strain and ECM
      protein. A concentration-dependant effect was observed with NaCl and KCl (0.1
      0.85%) on attachment of E. coli M23Sr, but only to collagen I. One-tenth percent
      CaCl2 produced the highest level of attachment to ECM proteins for E. coli M23Sr
      and EC614. In contrast, higher concentrations of CaCl2 increased attachment of E.
      coli EC473 to collagen IV. Rinses containing TSP produced >95% reduction in
      attachment to all ECM proteins. These observations will assist in the design of
      targeted interventions to prevent or disrupt contamination of meat surfaces, thus
      improving meat safety and quality.

PMID- 23541205
TI  - Biochemical, antimicrobial and molecular characterization of a noncytotoxic
      bacteriocin produced by Lactobacillus plantarum ST71KS.
AB  - Lactobacillus (Lb.) plantarum ST71KS was isolated from homemade goat feta cheese
      and identified using biochemical and molecular biology techniques. As shown by
      Tricine-SDS-PAGE, this lactic acid bacterium produces a bacteriocin (ST71KS) with
      an estimated molecular weight of 5.0 kDa. Bacteriocin ST71KS was not affected by
      the presence of alpha-amylase, catalase and remained stable in a wide range of pH
      and after treatment with Triton X-100, Triton X-114, Tween 20, Tween 80, NaCl,
      SDS, urea and EDTA. This bacteriocin also remained active after being heated at
      100  degrees C for 2 h and even after 20 min at 121  degrees C; however, it was
      inactivated by proteolitic enzymes. Production of bacteriocin ST71KS reached 6400
      AU/mL during stationary growth phase of Lb. plantarum cultivated in MRS at 30 
      degrees C and 37  degrees C. Bacteriocin ST71KS displayed a bactericidal effect
      against Listeria monocytogenes strains 603 and 607 and did not adsorb to the
      producer cells. Lb. plantarum ST71KS harbors two bacteriocin genes with homology
      to plantaricin S and pediocin PA-1. These characteristics indicate that
      bacteriocin ST71KS is a class IIa bacteriocin. The peptide presented no toxic
      effect when tested in vitro with kidney Vero cells, indicating safe technological
      application to control L. monocytogenes in foods.

PMID- 23541206
TI  - Impact of inulin and okara on Lactobacillus acidophilus La-5 and Bifidobacterium
      animalis Bb-12 viability in a fermented soy product and probiotic survival under
      in vitro simulated gastrointestinal conditions.
AB  - The effect of inulin and/or okara flour on Lactobacillus acidophilus La-5 and
      Bifidobacterium animalis Bb-12 viability in a fermented soy product (FSP) and on
      probiotic survival under in vitro simulated gastrointestinal conditions were
      investigated throughout 28 days of storage at 4  degrees C. Employing a 2(2)
      design, four FSP trials were produced from soymilk fermented with ABT-4 culture
      (La-5, Bb-12, and Streptococcus thermophilus): FSP (control); FSP-I (with inulin,
      3 g/100 mL of soymilk); FSP-O (with okara, 5 g/100 mL); FSP-IO (with inulin +
      okara, ratio 3:5 g/100 mL). Probiotic viabilities ranged from 8 to 9 log cfu/g
      during the 28 days of storage, and inulin and/or okara flour did not affect the
      viability of La-5 and Bb-12. Bb-12 resistance to the artificial gastrointestinal
      juices was higher than for La-5, since the Bb-12 and La-5 populations decreased
      approximately 0.6 log cfu/g and 3.8 log cfu/g, respectively, throughout storage
      period. Even though the protective effect of inulin and/or okara flour on
      probiotic microorganisms was not significant, when compared to a fresh culture,
      the FSP matrix improved Bb-12 survival on day 1 of storage and may be considered
      a good vehicle for Bb-12 and could play an important role in probiotic protection
      against gastrointestinal juices.

PMID- 23541207
TI  - Control of foodborne pathogens on fresh-cut fruit by a novel strain of
      Pseudomonas graminis.
AB  - The consumption of fresh-cut fruit has substantially risen over the last few
      years, leading to an increase in the number of outbreaks associated with fruit.
      Moreover, consumers are currently demanding wholesome, fresh-like, safe foods
      without added chemicals. As a response, the aim of this study was to determine if
      the naturally occurring microorganisms on fruit are "competitive with" or
      "antagonistic to" potentially encountered pathogens. Of the 97 and 107 isolates
      tested by co-inoculation with Escherichia coli O157:H7, Salmonella and Listeria
      innocua on fresh-cut apple and peach, respectively, and stored at 20  degrees C,
      seven showed a strong antagonistic capacity (more than 1-log unit reduction). One
      of the isolates, CPA-7, achieved the best reduction values (from 2.8 to 5.9-log
      units) and was the only isolate able to inhibit E. coli O157:H7 at refrigeration
      temperatures on both fruits. Therefore, CPA-7 was selected for further assays.
      Dose-response assays showed that CPA-7 should be present in at least the same
      amount as the pathogen to adequately reduce the numbers of the pathogen. From the
      results obtained in in vitro assays, competition seemed to be CPA-7's mode of
      action against E. coli O157:H7. The CPA-7 strain was identified as Pseudomonas
      graminis. Thus, the results support the potential use of CPA-7 as a bioprotective
      agent against foodborne pathogens in minimally processed fruit.

PMID- 23541208
TI  - Substrate utilization during incubation in meat juice medium of psychrotolerant
      clostridia associated with blown pack spoilage.
AB  - Several new species of psychrophilic or psychrotolerant clostridia have been
      identified in recent years. Some of these may be involved in 'blown pack'
      spoilage (BPS) of vacuum packaged beef. Organisms that cause BPS must produce
      large volumes of gas while utilizing substrates available in raw meat. Therefore,
      Clostridium algoriphilum, Clostridium algidixylanolyticum, Clostridium bowmanii,
      Clostridium frigoris, Clostridium frigidicarnis, Clostridium gasigenes,
      Clostridium lacusfryxellense, Clostridium psychrophilum, Clostridium tagluense
      and Clostridium vincentii were grown in meat juice medium (MJM), and changes in
      substrate concentrations were monitored to assess the potential for gas
      production by each organism. All 10 species were able to grow exponentially on
      glucose with simultaneous hydrolysis of glycogen, reaching maximum values for
      absorbance at 600 nm of 0.3-1.90. All ceased growing when glucose and glycogen
      were still detectable in the growth medium. C. frigidicarnis utilized most of the
      amino acids available in MJM and reduced the concentration of total amino acids
      by 10 mM. The other 9 species caused little or no reduction in amino acid
      concentrations. C. algidixylanolyticum and C. frigidicarnis utilized glucose,
      glycogen and lactate simultaneously during growth and after growth ceased. C.
      algoriphilum and C. frigoris commenced utilization of lactate, while continuing
      utilization of glucose and glycogen, only after growth ceased, but utilization of
      lactate by C. algoriphilum was weak. C. psychrophilum ceased utilization of
      glucose and glycogen but initiated weak utilization of lactate after growth
      ceased. The other 5 species did not utilize any substrate after growth ceased.
      The utilization of glucose, glycogen and relatively large amounts of lactate by
      C. algidixylanolyticum, C. frigoris, and C. frigidicarnis after growth ceased
      indicates that these organisms have the potential to cause BPS. The other 7
      species appear to lack such potential.

PMID- 23541209
TI  - Characterization of the cultivable microbial community in a spinach-processing
      plant using MALDI-TOF MS.
AB  - A better and regular control of the production chain of fresh fruits and
      vegetables is necessary, because a contamination of the product by human- and
      phyto-pathogenic microorganisms may result in high losses during storage and
      poses a threat to human health. Therefore, detailed knowledge about the
      occurrence and the diversity of microorganisms within single processing steps is
      required to allow target-oriented produce safety control. Recently, matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) was successfully used to identify bacterial colonies. Bacteria can be
      identified with high accuracy by comparing them with generated spectra of a
      reference database. In this study, spinach and wash water samples were taken of
      the complete process line of a spinach-washing plant. Bacteria in the samples
      were grown on plate-count, Arcobacter selective, marine and blood agar. In total,
      451 colonies were evaluated by MALDI-TOF MS, 16S rRNA gene sequence and
      phylogenetic analysis. 50% of the detected species belonged to the class of
      Gammaproteobacteria. Firmicutes were present with 22%. Mostly, the detected
      species showed 16S rRNA gene sequence dissimilarities larger than 1% to known
      reference species and, hence, could not be assigned to a distinct species.
      However, many isolated species belonged to genera which contain pathogenic or
      opportunistic pathogenic bacteria. In addition, the bacterial diversity on the
      spinach surface increased after the first washing step indicating a process-borne
      contamination of the spinach.

PMID- 23541210
TI  - Detection of Escherichia coli via VOC profiling using secondary electrospray
      ionization-mass spectrometry (SESI-MS).
AB  - Escherichia coli O157:H7 (EC O157:H7), as well as its recently emerging non-O157
      relatives, are a notorious group of pathogenic bacteria associated with foodborne
      outbreaks. In this study, we demonstrated that secondary electrospray ionization
      mass spectrometry (SESI-MS) could be a rapid and accurate detection technology
      for foodborne pathogens. With SESI-MS volatile organic compound (VOC) profiling,
      we were able to detect and separate a group of eleven E. coli strains from two
      major foodborne bacteria, Staphylococcus aureus and Salmonella Typhimurium in
      three food modeling media. In addition, heatmap analysis of relative peak
      intensity show that there are six core peaks (m/z of 65, 91, 92, 117, 118 and
      119) present and at a similar intensity in all eleven E. coli strains at the
      experimental conditions we tested. These peaks can be considered conserved VOC
      biomarkers for E. coli species (robustly produced after just 4 h of growth).
      Bacterial strain-level differentiation was also attempted via VOC profiling, and
      we found that EC O157:H7 and EC O145 were differentiable from all other EC
      strains under the conditions investigated.

PMID- 23541211
TI  - Magnetic nano-beads based separation combined with propidium monoazide treatment
      and multiplex PCR assay for simultaneous detection of viable Salmonella
      Typhimurium, Escherichia coli O157:H7 and Listeria monocytogenes in food
      products.
AB  - We developed a rapid and reliable technique for simultaneous detection of
      Salmonella Typhimurium, Escherichia coli O157:H7 and Listeria monocytogenes that
      can be used in food products. Magnetic nano-beads (MNBs) based immunomagnetic
      separation (IMS) was used to separate the target bacterial cells while multiplex
      PCR (mPCR) was used to amplify the target genes. To detect only the viable
      bacteria, propidium monoazide (PMA) was applied to selectively suppress the DNA
      detection from dead cells. The results showed the detection limit of IMS-PMA-mPCR
      assay was about 10(2) CFU/ml (1.2 * 10(2) CFU/ml for S. Typhimurium, 4.0 * 10(2)
      CFU/ml for E. coli O157:H7 and 5.4 * 10(2) CFU/ml for L. monocytogenes) in pure
      culture and 10(3) CFU/g (5.1 * 10(3) CFU/g for S. Typhimurium, 7.5 * 10(3) CFU/g
      for E. coli O157:H7 and 8.4 * 10(3) CFU/g for L. monocytogenes) in spiking food
      products samples (lettuce, tomato and ground beef). This report has demonstrated
      for the first time, the effective use of rapid and reliable IMS combined with PMA
      treatment and mPCR assay for simultaneous detection of viable S. Typhimurium, E.
      coli O157:H7 and L. monocytogenes in spiked food samples. It is anticipated that
      the present approach will be applicable to simultaneous detection of the three
      target microorganisms for practical use.

PMID- 23541212
TI  - A "successful allele" at Campylobacter jejuni contingency locus Cj0170 regulates
      motility; "successful alleles" at locus Cj0045 are strongly associated with mouse
      colonization.
AB  - Campylobacter jejuni is an important foodborne pathogen of humans and its primary
      reservoir is the gastrointestinal (GI) tract of chickens. Our previous studies
      demonstrated that phase variation to specific "successful alleles" at C. jejuni
      contingency loci Cj0045 (successful alleles carry 9G or 10G homopolymeric tracts)
      and Cj0170 (successful allele carries a 10G homopolymeric tract) in C. jejuni
      populations is strongly associated with colonization and enteritis in C57BL/6 IL
      10 deficient mice. In the current study, we strengthened the association between
      locus Cj0170, Cj0045, and mouse colonization. We generated 8 independent strains
      derived from C. jejuni 11168 strain KanR4 that carried a Cj0170 gene disruption
      and these were all non motile. Two randomly chosen strains with the Cj0170 gene
      disruption (DM0170-2 and DM0170-6) were gavaged into mice. DM0170-2 and DM0170-6
      failed to colonize mice while the control strain that carried a
      "successful"Cj0170 10G allele was motile and did colonize mice. In parallel
      studies, when we inoculated C. jejuni strain 33292 into mice, the
      "unsuccessful"Cj0045 11G allele experienced phase variation to "successful" 9G
      and 10G alleles in 2 independent experiments prior to d4 post inoculation in mice
      while the "successful" 9G allele in the control strain remained stable through
      d21 post inoculation or shifted to other successful alleles. These data confirm
      that locus Cj0170 regulates motility in C. jejuni strain KanR4 and is a virulence
      factor in the mouse model. The data also support a possible role of locus Cj0045
      as a virulence factor in strain 33292 in infection of mice.

PMID- 23541213
TI  - Heat stress adaptation induces cross-protection against lethal acid stress
      conditions in Arcobacter butzleri but not in Campylobacter jejuni.
AB  - The ability of many bacteria to adapt to stressful conditions may later protect
      them against the same type of stress (specific adaptive response) or different
      types of stresses (multiple adaptive response, also termed cross-protection).
      Arcobacter butzleri and Campylobacter jejuni are close phylogenetic relatives
      that occur in many foods of animal origin and have been linked with human illness
      (mainly diarrhoea). In the present study, sublethal stress adaptation
      temperatures (48  degrees C and 10  degrees C) and mild and lethal acid
      conditions (pH 5.0 and pH 4.0) were determined for A. butzleri and C. jejuni. In
      addition, it was evaluated whether these sublethal stress adaptations cause
      specific adaptive responses or cross-protection against subsequent mild or lethal
      acid stresses in these bacteria. The studies were conducted in broth adjusted to
      the different conditions and the results were determined by the dilution series
      plating method. It was shown that heat stress adapted A. butzleri (incubated for
      2 h at 48  degrees C) were significantly more resistant to subsequent lethal acid
      stress (pH 4.0) than non-adapted cells at the 1 h time-point (p < 0.01 in
      Wilcoxon rank sum test). No specific adaptive responses against the stresses in
      A. butzleri or C. jejuni and no cross-protection in C. jejuni were found. The
      ability of heat stressed A. butzleri to tolerate later lethal acid conditions
      should be taken into account when designing new food decontamination and
      processing strategies.

PMID- 23541214
TI  - Patterns of disease and treatment of cold sores.
AB  - BACKGROUND: Cold sores are a common condition that can cause significant
      morbidity and mortality. Antivirals are the typical treatment for cold sores, but
      the ways in which these medications are used to treat cold sores are not well
      studied. PURPOSE: To determine the main treatments prescribed for cold sores and
      trends in their management over time. METHODS: A retrospective analysis of the
      National Ambulatory Medical Care Survey database was used to analyze outpatient
      visits for cold sores from 1993 to 2009. Patients were included in the data
      analysis if they had one of the following three diagnoses reported for their
      reason-for-visit codes: cold sores (CS), herpes simplex (HS) or herpes simplex
      with cold sores (HS/CS). RESULTS: There was a decreasing trend in the number of
      annual patient visits for cold sores. The majority of patients were mainly young
      to middle adulthood, white women. The top two most commonly prescribed
      medications were acyclovir followed by valacyclovir. Valacyclovir use increased
      in all three populations, while acyclovir use decreased. CONCLUSIONS: The trends
      observed may indicate that physicians are evolving their treatment strategies to
      implement newer antiviral medications. This may prove more efficacious for the
      treatment of cold sores.

PMID- 23541215
TI  - Synergistic effects of diosmetin with erythromycin against ABC transporter over
      expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and
      inhibition of MRSA pyruvate kinase.
AB  - Increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      worldwide with limited therapeutic options is a growing public health concern.
      Natural products have been shown to possess antibacterial actions against MRSA.
      Flavonoids from natural products have been shown to possess antibacterial actions
      against MRSA by antagonizing its resistance mechanisms. Diosmin and diosmetin are
      natural flavonoids found in a variety of citrus fruits. The aim of this study was
      to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and
      the in vitro enzymatic activity of a newly discovered MRSA drug target, pyruvate
      kinase (PK). By using a panel of MRSA strains with known resistant mechanisms,
      neither diosmin nor diosmetin was shown to possess direct antibacterial
      activities against all tested MRSA strains. However, in checkerboard assay, we
      found that diosmetin together with erythromycin, could synergistically inhibit
      the growth of ABC-pump overexpressed MRSA-RN4220/pUL5054, and time kill assay
      also showed that the antibacterial activities of diosmetin with erythromycin were
      bactericidal. Diosmetin was further shown to significantly suppress the MRSA PK
      activities in a dose dependent manner. In conclusion, the inhibition of MRSA PK
      by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux
      pump which might contribute to the antibacterial actions of diosmetin against
      MRSA.

PMID- 23541216
TI  - The effects of two health information texts on patient recognition memory: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the effects of two health information texts on patient
      recognition memory, a key aspect of comprehension. METHODS: Randomized controlled
      trial (N=60), comparing the effects of experimental and control colorectal cancer
      (CRC) screening texts on recognition memory, measured using a statement
      recognition test, accounting for response bias (score range -0.91 to 5.34). The
      experimental text had a lower Flesch-Kincaid reading grade level (7.4 versus
      9.6), was more focused on addressing screening barriers, and employed more
      comparative tables than the control text. RESULTS: Recognition memory was higher
      in the experimental group (2.54 versus 1.09, t=-3.63, P=0.001), including after
      adjustment for age, education, and health literacy (beta=0.42, 95% CI: 0.17,
      0.68, P=0.001), and in analyses limited to persons with college degrees
      (beta=0.52, 95% CI: 0.18, 0.86, P=0.004) or no self-reported health literacy
      problems (beta=0.39, 95% CI: 0.07, 0.71, P=0.02). CONCLUSION: An experimental CRC
      screening text improved recognition memory, including among patients with high
      education and self-assessed health literacy. PRACTICE IMPLICATIONS: CRC screening
      texts comparable to our experimental text may be warranted for all screening
      eligible patients, if such texts improve screening uptake.

PMID- 23541217
TI  - Spousal support in a behavior change intervention for cholesterol management.
AB  - OBJECTIVE: To evaluate spousal involvement in a nurse-led intervention for
      patients with high cholesterol in which patients set health goals and spouses
      learned support strategies. METHODS: Qualitative interviews were conducted with
      29 patients and 26 spouses who received the intervention during a trial.
      Interviews were stratified by patient LDL-C change (better, same, worse). Coded
      text was content analyzed, and organized into thematic matrices, with columns
      indicating individuals (spouse or patient) and rows indicating dyads. RESULTS:
      Patients and spouses reported no drawbacks to spousal involvement; some patients
      whose LDL-C did not improve wanted more focus on spouse health. Spouses said that
      the nurse's expertise and interest were helpful and they were better able to
      communicate with patients about health. Although the program helped couples work
      together, spouses with better or same LDL-C talked more about functioning as a
      unit, whereas those whose partners had worse LDL-C talked more about functioning
      as individuals. CONCLUSION: Although the spousal role was accepted, there were
      variations in level of involvement. More active spousal involvement might relate
      to better patient outcomes. For less involved spouses, more focus on their health
      may improve commitment or involvement. PRACTICE IMPLICATIONS: These findings can
      inform ways to generate spousal support in future trials.

PMID- 23541218
TI  - Synthesis of [5]helicenes with a substituent exclusively on the interior side of
      the helix by metal-catalyzed cycloisomerization.
AB  - [5]Helicenes with a substituent exclusively oriented toward the interior
      curvature of the helix are synthesized by metal-catalyzed cycloisomerization. In
      addition, novel azulene-fused helicenes have been found through
      cycloisomerization studies. These [5]helicenes shows a high enough
      configurationally stability to allow resolution by HPLC on a chiral stationary
      phase.

PMID- 23541219
TI  - Correction to Sampling a Biomarker of the Human Immunodeficiency Virus across a
      Synthetic Nanopore.

PMID- 23541220
TI  - A rapid, ensemble and free energy based method for engineering protein
      stabilities.
AB  - Engineering the conformational stabilities of proteins through mutations has
      immense potential in biotechnological applications. It is, however, an inherently
      challenging problem given the weak noncovalent nature of the stabilizing
      interactions. In this regard, we present here a robust and fast strategy to
      engineer protein stabilities through mutations involving charged residues using a
      structure-based statistical mechanical model that accounts for the ensemble
      nature of folding. We validate the method by predicting the absolute changes in
      stability for 138 experimental mutations from 16 different proteins and enzymes
      with a correlation of 0.65 and importantly with a success rate of 81%. Multiple
      point mutants are predicted with a higher success rate (90%) that is validated
      further by comparing meosphile-thermophile protein pairs. In parallel, we devise
      a methodology to rapidly engineer mutations in silico which we benchmark against
      experimental mutations of ubiquitin (correlation of 0.95) and check for its
      feasibility on a larger therapeutic protein DNase I. We expect the method to be
      of importance as a first and rapid step to screen for protein mutants with
      specific stability in the biotechnology industry, in the construction of
      stability maps at the residue level (i.e., hot spots), and as a robust tool to
      probe for mutations that enhance the stability of protein-based drugs.

PMID- 23541221
TI  - Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer.
AB  - INTRODUCTION: The HOXB13 pGly84Glu mutation has recently been associated with an
      increased risk of prostate cancer but the association of other cancer sites with
      this allele has not been assessed. Data has suggested that HOXB13 expression
      levels are decreased in colorectal cancer (CRC) cell lines indicating this gene
      may be involved in colorectal tumourigenesis. METHODS: To evaluate a potential
      association of this mutation with CRC, we genotyped the mutation in 2695 CRC
      cases and 4593 controls from population-based registries in Canada and Australia.
      RESULTS: The HOXB13 pGly84Glu mutation was more common in CRC cases than controls
      (0.48% vs. 0.17%, P=0.02) indicating a significant association between the HOXB13
      variant and CRC risk (OR=2.8; 95%CI: 1.2-6.8). This association was attenuated
      but remained significant with the inclusion of previously published and publicly
      available genotype data. Pedigree analysis of cases and controls revealed that
      7/21 HOXB13 mutation carriers had a family history of prostate cancer.
      DISCUSSION: This report is the first to suggest a risk of CRC associated with
      mutations in the HOXB13 gene. These findings require further validation but may
      be of importance in the screening and genetic counseling of families known to
      carry the HOXB13 pGly84Glu mutation.

PMID- 23541222
TI  - Impact of objectively measured sedentary behaviour on changes in insulin
      resistance and secretion over 3 years in the RISC study: interaction with weight
      gain.
AB  - AIMS: The importance of reducing sedentary time is increasingly being recognized
      in the prevention of diabetes and cardiovascular disease. Despite this, the
      prospective association between sedentary time and physical activity with insulin
      sensitivity and cardiometabolic risk factors has been little studied. METHODS: In
      an analysis of data from the European RISC study, sedentary time and time spent
      in activity of moderate or vigorous intensity were assessed by accelerometry at
      baseline in 313 men and 414 women, aged 30-60 years, with insulin sensitivity as
      measured by euglycaemic-hyperinsulinaemic clamp. Three years later,
      cardiometabolic risk factors (anthropometry, glucose, insulin, lipids) were
      available for 549 participants. RESULTS: In cross-sectional analyses using
      baseline data, after adjusting for age, gender, recruitment centre and time spent
      in activity of moderate or vigorous intensity, significant unfavourable
      associations were observed between higher sedentary time with body weight, HDL
      cholesterol, triglycerides, clamp-measured insulin sensitivity and insulin
      secretion (all P(trend)<0.002). Sedentary time remained significantly associated
      with insulin secretion after adjusting for insulin sensitivity (P(trend)=0.02).
      In longitudinal analyses, higher baseline sedentary time was associated with 3
      year increases in fasting glucose, fasting insulin and the HOMA insulin
      resistance index score for the 50% of the study population who increased their
      BMI by at least 0.3 kg/m(2) (all P(trend)<0.01); these relationships remained
      significant after adjusting for time spent in activity of moderate or vigorous
      intensity. The 3-year increase in insulin secretion was lower in those spending
      more time doing activity of moderate or vigorous intensity (P(trend)=0.03).
      CONCLUSION: These prospective data suggest that less sedentary behaviour may
      partly counteract some of the negative effects of increasing body weight on
      glucose-insulin homoeostasis.

PMID- 23541223
TI  - An alternative for short renal vein during kidney transplantation: long-term
      experience with polyethylene terephthalate (Dacron) vascular graft.
AB  - OBJECTIVE: To describe the first long-term experience with the polyethylene
      perephthalate vascular graft to lengthen a short renal vein during kidney
      transplantation. MATERIALS AND METHODS: The polyethylene terephthalate vascular
      graft was interposed between the short renal vein of the donor kidney and the
      recipient's external iliac vein using 6-0 Prolene suture on a 13-mm needle. The
      postoperative follow-up protocol of the patients included regular serum
      creatinine levels and Doppler ultrasound scans. RESULTS: The median follow-up
      period was 74.5 months (range 51-128). Postoperative Doppler ultrasonography
      showed no complications in any of the patients. None of our patients experienced
      any kind of rejection. The median creatinine level at the last follow-up visit
      was 0.99 mg/dL (range 0.73-1.56). CONCLUSION: In our experience, the use of
      polyethylene terephthalate vascular grafts as a venous graft for the short renal
      vein in kidney transplantation provides an alternative option with long-term
      success.

PMID- 23541224
TI  - Editorial comment.

PMID- 23541225
TI  - SIU Scholar: Dr. John Samuel Banerji.

PMID- 23541226
TI  - SIU Scholar: Dr. Habibu Ahmed.

PMID- 23541227
TI  - Impaired detrusor contractility in a rat model of chronic bladder ischemia.
AB  - OBJECTIVE: To examine the effect of chronic ischemia associated with vascular
      disorders on bladder function, we investigated bladder contractility and changes
      in morphology and nerve distribution in a rat model of chronic bladder ischemia.
      METHODS: Adult male Sprague-Dawley rats were divided into arterial endothelial
      injury, sham, and control groups. The injury group underwent balloon endothelial
      injury of the iliac arteries and received a 2% cholesterol diet. The sham group
      was only incised bilaterally in the inguinal region and received the 2%
      cholesterol diet. The control group did not undergo any procedure and received a
      regular diet (0.09% cholesterol). All animals were euthanized after 8 weeks.
      Bladders were removed and weighed, and sections were used for muscle strip
      contraction and histologic analyses. Cross-sections of dissected common iliac
      arteries were examined histologically. RESULTS: Bladder contractile response and
      tension were significantly decreased in the injury group compared with the sham
      and control groups. Tissue from the injury group exhibited marked arterial
      occlusion with wall thickening. In the injury group, the collagen and muscle
      ratio (0.80 +/- 0.12) was significantly greater than in the control (P = .01) and
      sham (P = .04) groups. Significantly fewer protein gene product 9.5 (PGP9.5)
      positive nerve fibers were found in the injury group (513 +/- 53) than in the
      control (P = .01) and sham (P = .03) groups. CONCLUSION: Vascular occlusive
      disorders cause fibrosis and reduce the number of nerves innervating the bladder,
      which leads to decreased bladder contractility in a rat model of chronic bladder
      ischemia.

PMID- 23541228
TI  - Reply: To PMID 23541224.

PMID- 23541229
TI  - The role of Toll-like receptor (TLR) 2 and 9 in renal ischemia and reperfusion
      injury.
AB  - OBJECTIVE: To determine the involvement of Toll-like receptor (TLR) 2, TLR9, and
      TLR2+9 in renal ischemia/reperfusion (I/R) injury. METHODS: Mice with gene knock
      out of TLR2, TLR9, and TLR2+9 underwent renal I/R injury. Tubular damage,
      expression of proinflammatory cytokines and chemokines, and kidney dysfunction
      were evaluated on different days after reperfusion. RESULTS: Mice deficient in
      TLR2, but not TLR9, were protected from renal I/R injury with less tubular
      damage, decreased cytokine production, and lower serum creatinine and urea levels
      than wild-type mice. TLR2+9 double-deficiency did not have an additional effect
      on tissue injury compared with TLR2 deficiency alone. CONCLUSION: These results
      suggest that activation of TLR2 signaling contributes to the pathogenesis of
      renal I/R injury, whereas TLR9 may be redundant for the development of this
      injury.

PMID- 23541230
TI  - Robotic retroperitoneal transvaginal natural orifice translumenal endoscopic
      surgery (NOTES) nephrectomy: feasibility study in a cadaver model.
AB  - OBJECTIVE: To evaluate the feasibility of pure robotic natural orifice
      translumenal endoscopic surgery (R-NOTES) nephrectomy. METHODS: Two R-NOTES
      nephrectomy approaches were attempted in 3 female cadavers. A single-port device
      was inserted through an incision in the posterior vaginal fornix. In the first
      approach, the peritoneal cavity was accessed in the lithotomy position. In the
      second approach, the retroperitoneum of 2 cadavers was accessed in the prone
      jackknife position. The ureter was identified and followed cranially. The hilum
      was stapled and the kidney was dissected. The specimen was extracted into a bag.
      The incision was closed with an open approach. RESULTS: The first approach was
      not possible because of collision of the robotic arms against the legs and
      limited bowel retraction. After modifying the approach, a right transvaginal R
      NOTES retroperitoneal nephrectomy was successfully completed, without adding
      extra ports. Time for setup was 128 minutes. Time to identify the ureter was 53
      minutes. Dissection and control of the renal pedicle was completed in 21 minutes.
      Time to complete the dissection and extraction of the kidney was 36 minutes. Time
      to complete the procedure was 238 minutes. There were no injuries to
      retroperitoneal organs or vessels. In the third cadaver, there was rectal injury
      during the access. We were unable to complete the procedure because of the
      cadaver height. CONCLUSION: Transvaginal R-NOTES nephrectomy is technically
      challenging but feasible in select female cadavers. Retroperitoneal approach in
      the prone jackknife position was instrumental in facilitating robotic access to
      the kidney through the vagina. Improvements in the technique and instrumentation
      are necessary to make this approach safe and reproducible.

PMID- 23541231
TI  - [Cognitive vulnerability to alcohol dependence: related neuroanatomic
      endophenotypes].
AB  - INTRODUCTION: Executive function impairments and high level of impulsivity may
      constitute heritable endophenotypes that confer predisposition for alcohol
      dependence. Brain volume abnormalities have also been reported in young, alcohol
      naive subjects at high risk (HR) for alcohol dependence, and linked to cognitive
      dysfunction. METHODS: This paper presents a literature review of magnetic
      resonance imaging (MRI) studies that examined brain volumes in adolescent/young
      adult HR offspring from families with multiple cases of alcohol dependence
      compared to low risk controls with no family history of alcohol or drug misuse.
      In some of these studies, executive functioning and externalizing symptoms were
      also assessed. RESULTS: In HR subjects, local white matter volume deficits were
      found in the corpus callosum and in the right orbito-frontal cortex, and lower
      fractional anisotropy in the left inferior longitudinal fasciculus and in the
      right optic radiation. Altered fronto-cerebellar connectivity has also been
      reported. Diminished gray matter volume of the cerebellar cortex was found in HR
      subjects, in the frontal, cyngulate and para-hippocampal gyri, and also in the
      amygdala, the thalamus and the cerebellum. These structural abnormalities have
      been associated with higher impulsivity level and executive function impairments,
      themselves markers of vulnerability to alcoholism. These premorbid cerebral
      abnormalities may increase the risk for developing an alcohol use disorder in HR
      subjects through atypical control processing. CONCLUSION: Brain abnormalities may
      potentially constitute an abnormal neural network that might underlie the risk
      towards alcohol dependence. These circuitry abnormalities might contribute to the
      reward deficiency, as well as impaired response inhibition that predict impulsive
      spectrum behavior, which are thought to represent the inherited vulnerability to
      alcohol dependence in HR individuals.

PMID- 23541232
TI  - Mobile health to improve tuberculosis care and control: a call worth making.
AB  - The use of mobile phones has substantially increased throughout the world over
      the last decade. This has opened up opportunities for the integration of mobile
      phones as health intervention tools in many aspects of health care, including
      prevention, diagnosis, data collection, treatment and adherence monitoring and
      surveillance. Several applications have been explored in human immunodeficiency
      virus care. The field of tuberculosis (TB) has not exploited the potential of
      mobile health (m-health) to the same extent, although the opportunities have been
      recognized. A number of proof-of-concept and pilot studies have been published on
      m-health in TB care, and an even larger number of studies are available in the
      grey literature. This article summarizes publications and recent developments at
      the intersection of TB care and m-health. We show that more rigorous studies
      evaluating different applications and implementation strategies are needed to
      establish an evidence base that serves to inform policy and decision making. We
      outline further areas of research that should be addressed and potential
      challenges that lie ahead if m-health applications are to enhance the
      accessibility and quality of TB care.

PMID- 23541233
TI  - Day-to-day cause-effect relations between cellular immune activity, fatigue and
      mood in a patient with prior breast cancer and current cancer-related fatigue and
      depression.
AB  - This study of a breast cancer patient with cancer-related fatigue (CaRF) and
      depression investigated the bidirectional cause-effect relations between cellular
      immune activity, fatigue and mood during 'life as it is lived'. The 49-year-old
      patient (breast cancer diagnosis 5 years earlier, severe CaRF and increase in
      depressiveness since then) collected her entire urine for 28 days in 12-h
      intervals (from 8 p.m. to 8 a.m. and from 8 a.m. to 8 p.m.; total: 55
      measurements) for the determination of urinary neopterin (immune activation
      marker) and creatinine levels using HPLC. Furthermore, she completed
      questionnaires twice each day (at approx. 8 a.m. and 8 p.m.), which yielded
      information on mood (3-Skalen-Eigenschaftsworterliste [EWL]) and fatigue levels
      (visual analog scale [VAS]). Cross-correlational analyses showed complex
      connections between urinary neopterin concentrations and mood and fatigue in
      terms of direction of effect, temporal delay and response pattern. Increases in
      urinary neopterin levels significantly preceded increases in fatigue intensity
      with a temporal delay of 60-72h (lag 5: r=0.298; p=0.027), whereas increases in
      positive mood co-occurred with neopterin level increases (lag 0: r=+0.302;
      p=0.025) and preceded decreases in neopterin concentrations with a temporal delay
      of 132-144h (lag 11: r=-0.323; p=0.017). These results confirm and extend our
      previous findings and show that in order to obtain an adequate understanding of
      the dynamic relations among cancer-related variables, the characteristics of
      everyday-life conditions need to be considered. 

PMID- 23541236
TI  - Phenyl isocyanate anion radicals and their cyclotrimerization to triphenyl
      isocyanurate anion radicals.
AB  - Room-temperature sodium metal reduction of phenyl isocyanate (PhNCO) in
      hexamethylphosphoramide yields the anion radical (PhNCO(*-)) where the unpaired
      electron exhibits coupling to one nitrogen and five unique protons. The extent of
      coupling to the carbon in the NCO group was obtained via the reduction of (13)C
      labeled PhN(13)CO. Remarkably, this coupling is over 2 orders of magnitude
      smaller than that found for the alkyl-substituted analogue. This large
      attenuation indicates that the electron is not localized within the isocyanate
      group (as in the alkyl analogues) but is distributed throughout the entire pi
      system including the phenyl ring. The consequence of this delocalization is that
      the isocyanate is expected to remain linear upon reduction of PhNCO. The anion
      radicals of p-tolyl- and p-methoxyphenyl isocyanate have also been generated. We
      find that these electron-donating substituents on the phenyl ring have little
      effect on the nitrogen coupling. Hence, the NCO group has the same geometry as
      the PhNCO(*-). When PhNCO is reduced in tetrahydrofuran, a solvent where ion
      association effects are common, PhNCO(*-) is not observed. Here, a
      cyclotrimerization occurs (initiated by PhNCO(*-)), generating the triphenyl
      isocyanurate anion radical where the unpaired electron is predominately localized
      in one of the carbonyl moieties.

PMID- 23541235
TI  - Conversion strategy using an expanded genetic alphabet to assay nucleic acids.
AB  - Methods to detect DNA and RNA (collectively xNA) are easily plagued by noise,
      false positives, and false negatives, especially with increasing levels of
      multiplexing in complex assay mixtures. Here, we describe assay architectures
      that mitigate these problems by converting standard xNA analyte sequences into
      sequences that incorporate nonstandard nucleotides (Z and P). Z and P are extra
      DNA building blocks that form tight nonstandard base pairs without cross-binding
      to natural oligonucleotides containing G, A, C, and T (GACT). The resulting
      improvements are assessed in an assay that inverts the standard Luminex xTAG
      architecture, placing a biotin on a primer (rather than on a triphosphate). This
      primer is extended on the target to create a standard GACT extension product that
      is captured by a CTGA oligonucleotide attached to a Luminex bead. By using
      conversion, a polymerase incorporates dZTP opposite template dG in the absence of
      dCTP. This creates a Z-containing extension product that is captured by a bead
      bound oligonucleotide containing P, which binds selectively to Z. The assay with
      conversion produces higher signals than the assay without conversion, possibly
      because the Z/P pair is stronger than the C/G pair. These architectures improve
      the ability of the Luminex instruments to detect xNA analytes, producing higher
      signals without the possibility of competition from any natural oligonucleotides,
      even in complex biological samples. 

PMID- 23541234
TI  - Immune dysregulation and glucocorticoid resistance in minority and low income
      pregnant women.
AB  - Chronic prenatal stress contributes to poor birth outcomes for women and infants.
      Importantly, poor birth outcomes are most common among minority and low income
      women. To investigate underlying mechanisms, we tested the hypothesis that
      chronic stress related to minority or low income status is associated with
      glucocorticoid resistance as indicated by disruption in the cytokine
      glucocorticoid feedback circuit. Home visits were conducted during which 3rd
      trimester pregnant women completed stress and depression surveys and provided
      blood for pro- and anti-inflammatory cytokines. Saliva was collected 5 times the
      preceding day for diurnal cortisol levels. For statistical analyses, women were
      grouped 3 ways, by race, income, and the presence or absence of either of those
      risk factors; this last group was labeled high or low general risk. Immune
      regulation was evaluated by evidence of a functioning negative feedback
      relationship between cytokines and cortisol. Of 96 participants, 18 were
      minority, 22 of low income, and 29 either minority or low income (high general
      risk). Pearson partial correlation identified a significant negative relationship
      between cortisol area under the curve (AUC) and pro- to anti-inflammatory
      cytokine ratios in the low general risk women (i.e., Caucasian, higher income)
      including IFNgamma/IL10 (r=-0.73, p<0.0001), IL6/IL10 (r=-0.38, p=0.01),
      IL1beta/IL10 (r=-0.44, p=0.004) and TNFalpha/IL10 (r=-0.41; p=0.005); no such
      correlations existed in the high general risk women (i.e., minority, low income)
      for (IFNgamma/IL10: r=-0.25, p=0.43; IL6/IL10: r=0.12, p=0.70; IL1 beta/IL10:
      r=0.05, p=0.87; TNFalpha/IL10: r=0.10; p=0.75), suggestive of glucocorticoid
      resistance. Cortisol levels throughout the day also were higher in minority and
      high general risk groups (p<0.05). Without cytokine glucocorticoid feedback, a
      pregnant woman's ability to regulate inflammation is limited, potentially
      contributing to adverse maternal and infant outcomes. 

PMID- 23541237
TI  - Toward a personalized chronotherapy of high blood pressure and a circadian
      overswing.
AB  - Timing can greatly affect the response to a stimulus, including antihypertensive
      medications. Herein, we assess the response of 30 patients to
      losartan/hydrochlorothiazide (L/H), administered for at least 1 month at a given
      circadian stage to each patient, this stage being changed during consecutive
      spans to cover six treatment times from awakening to bedtime at approximately 3
      hour intervals. At the end of each stage, each patient underwent a 7-day around
      the-clock ambulatory blood pressure (BP) profile, analyzed chronobiologically. A
      larger reduction of the midline estimating statistic of rhythm (MESOR; a rhythm
      adjusted mean) of diastolic BP was achieved by L/H administration in the early
      morning for more patients (P < .05), while treatment upon awakening was the best
      choice for most patients to reduce the circadian amplitude of BP the most (P <
      .01). The optimal treatment time varied considerably among patients, however.
      Special attention should be given to the effect on the circadian amplitude since
      treatment can increase it above a threshold, beyond which there is a marked
      increase in cardiovascular disease risk. The results indicate the desirability to
      individualize the optimization of the antihypertensive effect of L/H by timing
      along the circadian scale.

PMID- 23541242
TI  - The impact of cognitive behavioral therapy on IL-6 levels in unmedicated women
      experiencing the first episode of depression: a pilot study.
AB  - A group of 11 women (18-29 years old) in the first episode of depression was
      evaluated before and after cognitive behavioral therapy (CBT). Depressive scores,
      assessed by Hamilton Rating Scale (HRSD), and serum IL-6 levels significantly
      decreased after the seventh session. These results suggest that CBT reduced both
      depressive symptoms and the inflammatory state in women. 

PMID- 23541243
TI  - Ego-syntonicity and ego-dystonicity of eating-related intrusive thoughts in
      patients with eating disorders.
AB  - The main objective of the present study was to analyse the role of the ego
      dystonicity and ego-syntonicity of eating disorder intrusive thoughts (EDITs) in
      the genesis and maintenance of eating disorders (EDs). Participants were 98
      female patients with EDs, 56 Spanish and 42 English (27.19+/-9.59 years; body
      mass index (BMI): 18.72+/-2.87). All of them completed the eating attitudes test,
      the Eating Attitudes Test, the Eating Intrusive Thoughts Inventory, the Ego
      Dystonicity Questionnaire-Reduced version, and the Ego-Syntonicity Questionnaire.
      Patients indicated that their EDITs were rational and also undesirable and
      immoral, suggesting that EDITs are not fully ego-syntonic or ego-dystonic.
      Multivariate analysis of variance (MANOVA) indicated no differences in ego
      syntonicity and ego-dystonicity across ED subtypes. Path analyses were performed
      to investigate the mediating role of the EDITs' ego-syntonicity and ego
      dystonicity in their interference, dysfunctional appraisals and control
      strategies. They showed, first, that the more interference an EDIT caused, the
      more ego-syntonic and the less ego-dystonic it was and, second, that when the
      EDITs were assessed as ego-syntonic, patients tried to do what they indicated,
      whereas when they were assessed as ego-dystonic, patients made efforts to
      neutralise them. Clinical implications for the conceptualisation and treatment of
      ED are discussed.

PMID- 23541244
TI  - A model of suicidal behavior in posttraumatic stress disorder (PTSD): the
      mediating role of defeat and entrapment.
AB  - The aim of this study was to examine whether depression, hopelessness and
      perceptions of defeat and entrapment mediated the effects of posttraumatic stress
      disorder (PTSD) symptoms on suicidal behavior. Participants were 73 individuals
      (mean age=29.2, S.D.=10.9, 79.5% female) diagnosed with current or lifetime PTSD
      who reported at least one PTSD symptom in the past month. Participants completed
      a series of self-report measures assessing depression, hopelessness and
      perceptions of defeat and entrapment. The Clinician Administrated Posttraumatic
      Scale for DSM-IV was administered to assess the presence and severity of PTSD
      symptoms. The results of Structural Equation Modeling supported a model whereby
      perceptions of defeat and entrapment fully mediated the effects of PTSD symptom
      severity upon suicidal behavior. The finding that perceptions of defeat and
      entrapment mediate the relationship between PTSD symptom severity and suicidal
      behavior was replicated in a subgroup of participants (n=50) who met the full
      criteria for a current PTSD diagnosis. The results support a recent theoretical
      model of suicide (The Schematic Appraisal Model of Suicide) which argues that
      perceptions of defeat and entrapment have a key role in the development of
      suicidal behaviors. We discuss the clinical implications of the findings. 

PMID- 23541245
TI  - Schizotypal traits are associated with poorer identification of emotions from
      dynamic stimuli.
AB  - Recent research suggests that the emotion recognition difficulties seen in
      schizophrenia may also be present to a lesser degree in non-clinical individuals
      who report attenuated expressions of schizophrenia-like symptoms (schizotypy).
      However, evidence in non-clinical samples primarily comes from studies employing
      static facial emotion tasks, and it is not clear whether poorer emotion
      recognition in schizotypy persists when people have access to a broader range of
      emotional cues more representative of typical face-to-face social interactions. A
      community sample of 151 adults completed measures of schizotypal traits, IQ, and
      a task that assessed emotion recognition using dynamic video-based stimuli.
      Global schizotypy and positive schizotypal traits were each associated with
      poorer emotion recognition. Negative schizotypy was not associated with emotion
      recognition overall, but was associated with errors in recognising positive
      emotions. It appears that poorer emotion recognition in schizotypy is not limited
      to single-channel stimuli, but can be seen even when multiple emotional cues are
      available. Thus, individuals with high levels of schizotypal traits, and positive
      features in particular, may have greater difficulty when it comes to 'reading'
      the emotions of others in everyday social interactions.

PMID- 23541246
TI  - Ribosomal DNA transcription in the anterior cingulate cortex is decreased in
      unipolar but not bipolar I depression.
AB  - The anterior cingulate cortex (AC) is consistently implicated in the
      pathophysiology of depression. However, it is not clear whether unipolar and
      bipolar depression display distinct neuropathological features. Therefore, the
      objective of this post-mortem study was to re-evaluate this important issue.
      Brains from 9 patients with major depressive disorder (MDD) and 11 patients with
      bipolar disorder (BD) subtype I depression as well as 24 matched controls were
      analysed. The argyrophilic nucleolar organiser region (AgNOR) silver-staining
      method was applied on paraffin-embedded brain sections in order to assess the
      transcriptional activity of ribosomal DNA (rDNA) in layer III and V pyramidal
      neurons of the dorsal and ventral AC in both hemispheres. An AgNOR area decrease
      suggestive of a diminished transcriptional activity of rDNA was found in the MDD
      group both versus controls and versus the BD group. The effect was specific for
      the right hemisphere and dorsal AC and was restricted to layer V pyramidal
      neurons. The results suggest that only patients with MDD display region-specific
      chronic hypoactivity of these output neurons, which are critical for mood
      regulation. Furthermore, in our cohort, unipolar and bipolar I depression could
      be differentiated relative to the presumed AC hypoactivity and psychotropic
      medication did not counteract the observed effect. 

PMID- 23541247
TI  - Analysis of tubal patency after essure placement.
AB  - STUDY OBJECTIVE: To evaluate tubal patency after hysteroscopic sterilization
      using the Essure microinsert (Conceptus Inc, San Carlos, CA). DESIGN: A
      retrospective longitudinal cohort study. DESIGN CLASSIFICATION: II-3. SETTING:
      Patients undergoing hysteroscopic sterilization in the outpatient clinic of a
      university-based hospital in Southeast Texas from July 2009 to November 2011.
      PATIENTS: Two hundred twenty-nine women (ages 21-44 yrs, 71% Hispanic) desiring
      sterilization with a history of regular menses, demonstrated prior fertility (>=1
      live birth), and the ability to use an alternative contraceptive method for at
      least 90 days after coil placement were included. Twenty six patients in this
      cohort were excluded because of failure to perform a hysterosalpingogram (HSG),
      tubal perforation, severe dyspareunia, a history of ectopic pregnancy, tubal
      surgery, or cervical intraepithelial neoplasia. INTERVENTIONS: Not applicable.
      MEASUREMENTS AND MAIN RESULTS: HSGs were assessed for microinsert location and
      tubal occlusion. Two hundred three patients were included for analysis. After the
      successful bilateral hysteroscopic placement of Essure microinserts in fallopian
      tubes, all patients returned for the first follow-up HSG a mean of 103 +/- 38
      days after the procedure. Patients with fallopian tube patency at the initial HSG
      returned for second and/or third HSGs as needed at 192 +/- 45 and 291 +/- 97
      days, respectively. Correct device placement was confirmed in 100% of cases at
      the first HSG. The tubal patency rates at the 90-day and 180-day HSGs were 16.1%
      (95% confidence interval, 7.4%-31.7%) and 5.8% (95% CI, 1.2%-24.4%),
      respectively. These rates were estimated by the accelerated failure time model
      with log normal distribution and interval censored time to event. The 16.1% 90
      day tubal patency rate is significantly different from the 8% rate reported by
      Cooper et al in the 2003 multicenter phase III pivotal trial (p <.001).
      CONCLUSION: Our data indicate that hysteroscopic sterilization with Essure
      results in a higher initial tubal patency rate than previously reported.
      Multivariate analyses are needed to identify factors associated with an increased
      risk of postprocedure tubal patency.

PMID- 23541248
TI  - Cosmetic outcomes of laparoendoscopic single-site hysterectomy compared with
      multi-port surgery: randomized controlled trial.
AB  - STUDY OBJECTIVE: To compare cosmetic satisfaction with laparoendoscopic single
      site surgery (LESS) compared with multi-port surgery. DESIGN: Randomized
      controlled trial (Canadian Task Force classification I). SETTING: University
      hospital. PATIENTS: Twenty women who underwent laparoscopically-assisted vaginal
      hysterectomy (LAVH) via LESS or multi-port surgery. INTERVENTIONS:
      Laparoendoscopic single-site surgery or multi-port surgery. MEASUREMENT AND MAIN
      RESULTS: Cosmetic satisfaction was assessed using the Body Image Questionnaire at
      baseline and at 1, 4, and 24 weeks after surgery. Of the 20 LESS procedures, 1
      was converted to multi-port surgery because of severe adhesions, and 1 woman
      assigned to undergo multi-port surgery was lost to follow-up. The 2 surgery
      groups did not differ in clinical demographic data and surgical results or
      postoperative pain scores at 12, 24, and 36 hours. Compared with the multi-port
      group, the LESS group reported significantly higher cosmetic satisfaction at 1,
      4, and 24 weeks after surgery (p < .01). CONCLUSION: Compared with multi-port
      surgery, LESS is not only a feasible approach with comparable operative outcomes
      but also has an advantage insofar as cosmetic outcome.

PMID- 23541249
TI  - Screening Hofmann compounds as CO2 sorbents: nontraditional synthetic route to
      over 40 different pore-functionalized and flexible pillared cyanonickelates.
AB  - A simple reaction scheme based on the heterogeneous intercalation of pillaring
      ligands (HIPLs) provides a convenient method for systematically tuning pore size,
      pore functionality, and network flexibility in an extended series of pillared
      cyanonickelates (PICNICs), commonly referred to as Hofmann compounds. The
      versatility of the approach is demonstrated through the preparation of over 40
      different PICNICs containing pillar ligands ranging from ~4 to ~15 A in length
      and modified with a wide range of functional groups, including fluoro, aldehyde,
      alkylamine, alkyl, aryl, trifluoromethyl, ester, nitro, ether, and nonmetalated
      4,4'-bipyrimidine. The HIPL method involves reaction of a suspension of preformed
      polymeric sheets of powdered anhydrous nickel cyanide with an appropriate pillar
      ligand in refluxing organic solvent, resulting in the conversion of the planar
      [Ni2(CN)4]n networks into polycrystalline three-dimensional porous frameworks
      containing the organic pillar ligand. Preliminary investigations indicate that
      the HIPL reaction is also amenable to forming Co(L)Ni(CN)4, Fe(L)Ni(CN)4, and
      Fe(L)Pd(CN)4 networks. The materials show variable adsorption behavior for CO2
      depending on the pillar length and pillar functionalization. Several compounds
      show structurally flexible behavior during the adsorption and desorption of CO2.
      Interestingly, the newly discovered flexible compounds include two flexible
      Fe(L)Ni(CN)4 derivatives that are structurally related to previously reported
      porous spin-crossover compounds. The preparations of 20 pillar ligands based on
      ring-functionalized 4,4'-dipyridyls, 1,4-bis(4-pyridyl)benzenes, and N-(4
      pyridyl)isonicotinamides are also described.

PMID- 23541250
TI  - Chaos as a social determinant of child health: Reciprocal associations?
AB  - This study informs the social determinants of child health by exploring an
      understudied aspect of children's social contexts: chaos. Chaos has been
      conceptualized as crowded, noisy, disorganized, unpredictable settings for child
      development (Evans, Eckenrode, & Marcynyszyn, 2010). We measure chaos at two
      levels of children's ecological environment - the microsystem (household) and the
      mesosystem (work-family-child care nexus) - and at two points in early childhood
      (ages 3 and 5). Using data from the Fragile Families and Child Wellbeing Study (N
      = 3288), a study of predominantly low-income women and their partners in large US
      cities, we develop structural equation models that assess how maternal-rated
      child health (also assessed at ages 3 and 5) is associated with latent constructs
      of chaos, and whether there are important reciprocal effects. Autoregressive
      cross-lagged path analysis suggest that increasing chaos (at both the household
      and maternal work levels) is associated with worse child health, controlling for
      key confounders like household economic status, family structure, and maternal
      health status. Child health has little effect on chaos, providing further support
      for the hypothesis that chaos is an important social determinant of child health
      in this sample of relatively disadvantaged children. This suggests child health
      may be improved by supporting families in ways that reduce chaos in their home
      and work/family environments, and that as researchers move beyond SES, race, and
      family structure to explore other sources of health inequalities, chaos and its
      proximate determinants may be a promising avenue for future research. 

PMID- 23541251
TI  - Cost-effectiveness of primary antifungal prophylaxis with posaconazole versus
      itraconazole in allogeneic hematopoietic stem cell transplantation.
AB  - PURPOSE: To evaluate the cost-effectiveness of posaconazole vs itraconazole in
      the prevention of invasive fungal infections (IFIs) in recipients of allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). METHODS: Total hospital
      based costs from initial admission for allo-HSCT until day 100 after
      transplantation were evaluated for 49 patients in whom the clinical efficacy of
      antifungal prophylaxis with posaconazole vs itraconazole had been previously
      analyzed and reported. Clinical and economic data were used to determine the
      incremental costs per IFI avoided and per life-year gained for posaconazole
      compared with itraconazole. Confidence intervals for the incremental cost
      effectiveness ratio (ICER) and a cost-effectiveness acceptability curve were
      estimated through bootstrapping with the bias-corrected percentile method.
      RESULTS: According to our analysis, the total cost of allo-HSCT per patient
      during the 100-day fixed-treatment period was ?46,562 in the posaconazole group
      (n = 33) and ?45,080 in the itraconazole group (n = 16). However, the reduction
      in the incidence of IFI and the improved outcome with posaconazole resulted in a
      favorable ICER of ?11,856 per IFI avoided and ?5218 per life-year gained. With
      the outcomes of the bootstrap procedure, the cost-effectiveness acceptability
      curve was constructed. Assuming a threshold of ?30,000 per life-year gained, the
      ICER based on life-years gained is acceptable with 75% certainty. LIMITATIONS:
      This evaluation is based on data from a single-center, non-randomized study.
      Preference weights or utilities were not available to calculate quality-adjusted
      life-years. Extra-mural costs were only partially evaluated from a hospital
      perspective. Indirect costs and economic consequences are not included.
      CONCLUSIONS: This economic evaluation compared direct medical costs associated
      with posaconazole or itraconazole treatment; the data suggest that posaconazole
      may be cost-effective as antifungal prophylaxis during the early high-risk
      neutropenic period and up to 100 days after allo-HSCT.

PMID- 23541252
TI  - Words of wisdom: Re: Do adenocarcinomas of the prostate with Gleason Score (GS)
      <= 6 have the potential to metastasize to lymph nodes?

PMID- 23541253
TI  - Words of wisdom: Re: Marital status: a gender-independent risk factor for poorer
      survival after radical cystectomy.

PMID- 23541254
TI  - Words of wisdom: Re: Abiraterone in metastatic prostate cancer without previous
      chemotherapy.

PMID- 23541255
TI  - Words of wisdom: Re: Population based study of long-term rates of surgery for
      urinary incontinence after radical prostatectomy for prostate cancer.

PMID- 23541256
TI  - Words of wisdom: Re: Objective measures of renal mass anatomic complexity predict
      rates of major complications following partial nephrectomy.

PMID- 23541257
TI  - Words of wisdom: Re: Precise segmental renal artery clamping under the guidance
      of dual-source computed tomography angiography during laparoscopic partial
      nephrectomy.

PMID- 23541258
TI  - Review of sn-2 palmitate oil implications for infant health.
AB  - Human milk provides the optimal balanced nutrition for the growing infant in the
      first months after birth. The human mammary gland has evolved with unusual
      pathways, resulting in a specific positioning of fatty acids at the outer sn-1
      and sn-3, and center sn-2 of the triacylglyceride, which is different from the
      triglycerides in other human tissues and plasma. The development of structured
      triglycerides enables mimicking the composition as well as structure of human
      milk fat in infant formulas. Studies conducted two decades ago, together with
      very recent studies, have provided increasing evidence that this unusual
      positioning of 16:0 in human milk triglycerides has a significant role for infant
      health in different directions, such as fat and calcium absorption, bone health,
      intestinal flora and infant comfort. This review aims to unravel the relevance of
      human milk triglyceride sn-2 16:0 for intestinal health and inflammatory pathways
      and for other post-absorption effects. 

PMID- 23541259
TI  - Perceived policy effectiveness and recycling behaviour: the missing link.

PMID- 23541261
TI  - Report from the 4th International Symposium on Energy from Biomass and Waste:
      Venice 2012.

PMID- 23541262
TI  - Inosine-specific cleavage of RNA for microarray analysis of RNA A-to-I editing
      targets.
AB  - Dysregulations of RNA A-to-I editing are associated with developmental defects in
      mouse and human diseases. Although several methods of identifying RNA A-to-I
      editing sites are currently available, most of the critical editing targets
      responsible for the important biological functions of adenosine deaminases that
      act on RNA (ADARs) remain unknown. Here we report a modified I-specific cleavage
      method that improves the quality of the RNA product. Preliminary microarray
      comparison of RNAs subjected to I-specific cleavage or mock digestion reported
      165 genes that showed more than 0.2-fold reductions due to the cleavage. Six of
      the 165 genes were randomly selected for further verification, and three were
      verified to be targets of I-specific cleavage. This method may provide an
      alternative method of identifying novel RNA A-to-I editing sites using a
      microarray and facilitate the inquiry into the roles of RNA A-to-I editing in
      various biological processes.

PMID- 23541263
TI  - The effect of atorvastatin on survival of rat ischemic flap.
AB  - Management of skin avulsion with tissue exposure is a challenge for plastic
      surgeons. Clinical observations have suggested that longer survival of skin flap
      prevents further contamination and infection. Less well known is the role of
      atorvastatin in avulsion skin flap. Therefore, we attempted to determine whether
      atorvastatin could alleviate avulsion skin flap in a rat model. Twenty male
      Sprague-Dawley rats were randomized into two groups: the atorvastatin group and
      the control. Before operation, each rat received an initial blood perfusion scan
      as baseline data. Then, each rat received an operation of skin flap incision,
      elevation, and resuturing to the original position under general anesthesia.
      Another blood perfusion scan was performed on each rat 30 minutes, 4 days, and 7
      days postoperatively. On the 7th postoperative day, the necrotic area of skin
      flap was measured as the skin flap viability. The skin flap tissues at 2.5 and
      5cm distal to the skin flap base were collected for histopathological analysis,
      as well as measurement of vascular endothelial growth factor (VEGF) mRNA
      expression, and vascular density. Compared with 30 minutes postoperation, there
      was a significant increase in the ratio of skin flap blood perfusion on the 4th
      and 7th days postoperation in both control and atorvastatin groups (p<0.05).
      Compared with the control group, there was a significant decrease in necrotic
      area, significant increase in ratio of skin flap blood perfusion on postoperation
      days 4 and 7, and significant increase in vascular density under high field at
      2.5cm distal to the base of skin flap in the atorvastatin group (p<0.05). The
      VEGF121 and VEGF165 mRNA expression at 2.5cm distal to the base of skin flap
      differed significantly between the two groups (p<0.05). Compared with the control
      group, atorvastatin treatment improved skin flap blood perfusion, vascular
      density, and necrotic area dependent on VEGF mRNA expression.

PMID- 23541264
TI  - An experimental model of Stanford type B aortic dissection with intravenous
      epinephrine injection.
AB  - The aim of this study was to create an experimental model of aortic dissection
      (AD) with a long-term patent false lumen to develop new treatments for Stanford
      type B aortic dissection. Sixteen adult beagle dogs (weight 14-18 kg) were used.
      After exposure and partially clamping, the descending aorta was cut through the
      adventitia to one-third of the depth of the tunica media. The aortic wall was
      divided into two layers by raspatory. Then half the circumference of the inner
      layer was cut transversely. All of the proximal layers and the distal outer
      layers were anastomosed together. Epinephrine was immediately used to expand the
      false lumen, and the effect was terminated using nitroglycerin when necessary.
      All dogs underwent both digital subtraction angiography (DSA) and computed
      tomography angiography (CTA) immediately after and 1 week and 1 month after
      surgery. The dogs were followed up at 1 day, 3 months, 1 year, and 2 years. The
      surgery was successful in 12 dogs. Dissection formation was observed immediately
      after epinephrine administration and confirmed by DSA and CTA. Our results showed
      typical characteristics of AD, such as a tear, septum, and true and false lumens.
      This is an easy and feasible way of developing a Stanford type B AD model by
      intravenous injection of epinephrine. In this canine model of AD, the false lumen
      has excellent long-term patency and the dissection plane is histologically
      similar to that in human AD. This model may contribute to the development of new
      treatments for Stanford type B AD.

PMID- 23541265
TI  - Neoadjuvant chemotherapy improves survival rate in advanced urothelial carcinoma.
AB  - Radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy has been
      conventionally used for patients with advanced urothelial carcinoma (AUC). Recent
      research has indicated that systemic neoadjuvant chemotherapy (NC) with RS yields
      better outcomes than RS alone for patients with locally advanced bladder cancer.
      However, there are no reports indicating whether NC or AC would be beneficial for
      patients with AUC. The present study compared the survival rate for AUC patients
      receiving NC or AC. A retrospective analysis was conducted using data for 64
      patients with AUC who underwent RS and systemic chemotherapy at our institution
      between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS
      and 34 received RS followed by systemic AC. Pathologic stages (p=0.002), grades
      (p=0.018) and lymphovascular invasion (p=0.047) were significantly lower in the
      patients who received NC first than in those who received RC first. Furthermore,
      analysis of the surgical specimens revealed that 26.7% of patients who received
      NC before RS had complete remission. There were no significant differences in
      demographic data, surgical complications, and chemotoxicity between the two
      patient groups. The progression-free survival (PFS) and overall survival (OS) of
      patients who received initial NC were significantly better than those of patients
      who received initial RC (p=0.002 and 0.018, respectively). Our results indicate
      that NC administration before RS significantly improved the PFS and OS of AUC
      patients, without increasing surgical complications and chemotoxicity. Further
      prospectively controlled trials need to be conducted to confirm the effectiveness
      of NC for AUC patients.

PMID- 23541266
TI  - Relationship between low-density lipoprotein levels on admission and 1-year
      outcome in patients with acute ST-segment-elevation myocardial infarction.
AB  - This study assessed the relationship between low-density lipoprotein cholesterol
      (LDL-C) levels on admission and the incidence of major adverse cardiovascular
      events (MACE) in patients with acute ST-segment-elevation myocardial infarction
      (ASTEMI). Patients with ASTEMI who had a lipid profile tested within 24 hours of
      symptom onset were enrolled. They were stratified into high and low LDL-C groups
      according to whether their LDL-C was above (n = 501) or below (n = 575) the
      median level, respectively. The incidence of MACE, cardiovascular death, non
      fatal MI, revascularization, and stroke was compared between the groups at 1
      month, 6 months, and 1 year. Survival analysis and Cox proportional hazard
      analysis were performed. In-hospital use of beta blockers was better in the high
      than in the low LDL-C group (76.6% vs. 69.7%, p = 0.01). Statin use was
      significantly higher in the high than in the low LDL-C group during follow-up
      (86.8% vs. 80.0%, p = 0.003 at1 month; 71.6% vs. 62.4%, p = 0.002 at 6 months;
      67.8% vs. 61.2%, p = 0.03 at 1 year). The incidence of MACE on follow-up at 1
      month was higher in the low than in the high LDL-C group (12.0% vs. 8.1%, p =
      0.04). At 1 year, survival was not significantly different between the groups.
      Cox proportional hazards analysis indicated that the incidence of MACE was
      significantly associated with hypertension, current smoking, high-density
      lipoprotein cholesterol (HDL-C), in-hospital use of beta blockers, and statin use
      on follow-up (p < 0.01). LDL-C levels on admission in patients with ASTEMI had no
      significant effect on the 6-month and 1-year incidence of MACE, but the incidence
      of MACE was significantly higher in the low LDL-C group at 1 month. It would be
      relevant to further investigate the HDL-C level on admission, in-hospital use of
      beta blockers, and statin use during follow-up in relation to MACE.

PMID- 23541267
TI  - Chewing areca nut as an independent risk factor for proteinuria in middle-aged
      men.
AB  - No previous large-scale research has reported the association of chewing areca
      nut (AN) with proteinuria. The aim of this study was to investigate such an
      association in men over a 7-year study. In this cross-sectional research, we
      retrospectively reviewed the records of health check-ups in a community hospital
      setting from 2003 to 2009. Laboratory tests, medical histories, and the status of
      smoking cigarettes, drinking alcohol, and chewing AN were obtained for each
      participant. Proteinuria was defined as having +/- or heavier protein response
      (including +/- to 4+) in a urine test performed by an automated chemical
      analyzer. We compared characteristics in participants with and without
      proteinuria, and analyzed the adjusted risk for proteinuria with chewing AN in
      middle-aged men. We also compared the changes in adjusted risk for proteinuria
      under a stricter definition of proteinuria (>= 1+ proteinuria). There were 11,991
      men with a mean age of 58.94 +/- 12.06 years. The prevalence of proteinuria in AN
      chewers was 13.7%, and 11.2% for non-chewers (p = 0.005). Of the 1381
      participants with proteinuria, the proportion chewing AN was 15.3%, and 12.6% for
      those without proteinuria (p = 0.005). In the multivariate logistic regression
      analysis with three different levels of adjustment models, with adjustment
      factors for age, drinking, smoking, hypertension, diabetes, hyperlipidemia, body
      mass index, chronic kidney disease, anemia, liver dysfunction, and hyperuricemia,
      the odds ratios of proteinuria for chewing AN were 1.61, 1.55 and 1.40 (all p =
      0.000). With the stricter definition of proteinuria, the odds ratios became
      weaker (1.40, 1.36 and 1.19; p = 0.009, 0.029 and 0.24). We concluded that
      chewing AN was independently associated with risk of proteinuria in middle-aged
      Chinese men.

PMID- 23541268
TI  - Self-esteem in adolescent aggression perpetrators, victims and perpetrator
      victims, and the moderating effects of depression and family support.
AB  - The aims of this study were (1) to examine differences in the level of self
      esteem among adolescents with different roles in aggression involvement
      (aggression perpetrators, victims, perpetrator-victims and neutrals) according to
      gender and (2) to examine the moderating effects of depression and family support
      on association between aggression involvement and self-esteem. A total of 8085
      adolescents in Taiwan completed questionnaires. The relationships between self
      esteem and aggression involvement were examined by multiple regression analysis.
      The moderating effects of depression and family support on the association
      between aggression involvement and self-esteem were examined. The results showed
      that in females, aggression victims had lower self-esteem than those in the other
      three groups (t=-2.940 to 2.173, p<0.05); however, there was no significant
      difference in self-esteem among perpetrators, perpetrator-victims, and neutrals
      (t=0.693-0.933, p>0.05). In males, self-esteem in victims and perpetrator-victims
      was lower than in neutrals and perpetrators (t=-3.339 to -2.704, p<0.01);
      however, there was no difference in self-esteem between victims and perpetrator
      victims (t=-1.115, p>0.05) or between perpetrators and neutrals (t=-1.396,
      p>0.05). Family support had a moderating effect on the association between self
      esteem and victimization in males. Depression had a moderating effect on the
      association between self-esteem and perpetration-victimization and victimization
      in males. The results indicate that self-esteem in adolescents with different
      patterns of involvement in aggression is not the same as in those without
      involvement. The moderating effects of depression and family support should be
      considered when developing intervention strategies to raise self-esteem in
      adolescents with aggression involvement.

PMID- 23541269
TI  - Bone metastasis versus bone marrow metastasis? Integration of diagnosis by (18)F
      fluorodeoxyglucose positron emission/computed tomography in advanced malignancy
      with super bone scan: two case reports and literature review.
AB  - Super scan pattern on technetium-99m methyldiphosphonate (Tc-99m MDP) bone
      scintigraphy is a special condition of extremely high bone uptake relative to
      soft tissue with absent or faint renal radioactivity visualization, which is
      usually seen in diffuse bone metastases or discrete endocrine entities. Here, two
      cases with super bone scan are presented. One was a young man diagnosed with
      gastric cancer. The other was a middle-aged woman with a history of breast cancer
      with recent recurrence. Both cases had 18-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) diagnosis simultaneously. Based
      on imaging of (18)F-FDG PET/CT, diffusely incremental (18)F-FDG avidity in
      spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The
      cytological results of bone marrow biopsy showed evidence of malignant
      metastasis. However, there were several focal discrepant findings between the
      (18)F-FDG PET/CT and Tc-99m MDP bone scan. According to integration of both
      imaging findings and the result of bone marrow biopsy, we believe that the
      disseminated malignant spread in bone marrow is a primitive alternation in the
      super bone scan and that it is also as a result of neoplasm-related endocrine
      factors.

PMID- 23541270
TI  - Newly revised category for complex congenital cardiac segmental connections.

PMID- 23541271
TI  - Epidermal cyst of the bony external auditory canal.

PMID- 23541272
TI  - Striving for excellence: nurturing midwives' skills in Freetown, Sierra Leone.
AB  - Midwives provide critical, life-saving care to women and babies. Effective
      midwives must be clinically competent, with the required knowledge, skills, and
      attitudes to provide quality care. Their success depends on an environment of
      supportive supervision, continuing education, enabling policies, and access to
      equipment and referral facilities. In Freetown, Sierra Leone, the Aberdeen
      Women's Centre launched a maternity unit with an emphasis on striving for
      excellence and providing ongoing professional development to its staff midwives.
      Its success was built upon fostering a sense of responsibility and teamwork,
      providing necessary resources, conforming to evidence-based standards, and
      building partnerships. An explicit philosophy of care was crucial for guiding
      clinical decision making. In its first two years of operation, the Aberdeen
      Women's Centre assisted 2076 births with two maternal deaths and 92 perinatal
      deaths. In-service education and supportive supervision facilitated the midwives'
      professional growth, leading to capable future leaders who are providing
      exemplary care to delivering mothers and their newborns in Freetown. 

PMID- 23541273
TI  - Early neoplastic lymphoid lesions.
AB  - The differential diagnosis between neoplastic and reactive lymphoid
      proliferations is a relatively common situation, which in most cases is resolved
      using conventional morphological and phenotypic criteria. In the last years, a
      number of studies have identified different types of lymphoid lesions sharing
      pathological and molecular features of both benign and malignant processes that
      are difficult to interpret. A group of these lesions correspond to atypical
      lymphoid hyperplasias, including follicular hyperplasias, atypical marginal zone
      hyperplasias, and florid reactive lymphoid hyperplasias of the lower female
      genital tract in which immunoglobulin light chain restriction with or without
      clonal IGH rearrangements may be found in some cases. However, these lesions are
      usually self-limited and do not evolve to an overt lymphoid neoplasia. A second
      group of lesions are clonal expansions of cells with phenotypic or molecular
      features of well-defined lymphoid neoplasias, such as chronic lymphocytic
      leukemias, follicular lymphomas, or mantle cell lymphomas, occurring in otherwise
      healthy individuals or in the context of reactive lymphoid tissues. In this
      review, we discuss the criteria to distinguish these lesions from overt lymphomas
      and the current recommendations for the management of the individuals in which
      these lesions are found.

PMID- 23541274
TI  - Immunosuppressive and immunomodulatory therapy-associated lymphoproliferative
      disorders.
AB  - A variety of therapeutic agents may increase the risk of lymphoproliferative
      disorders/neoplasms. These include those agents used to treat other malignancies
      (i.e., cytotoxic chemotherapy) and those used to treat or prevent certain
      diseases (or graft rejection) that alter the immune system. This review is
      restricted to the secondary lymphoid disorders that are unrelated to primary DNA
      damage by cytotoxic chemotherapy, and thus will include discussions regarding
      post-transplant lymphoproliferative disorders and those lymphoproliferations
      associated with the therapy of autoimmune and other immune-mediated diseases.
      Three drugs, or classes of drugs, used in the treatment of autoimmune and other
      immune-mediated diseases are discussed in some detail. These include
      methotrexate, anti-metabolites (including thiopurines and mycophenolate mofetil),
      and immunomodulators. The appropriate recognition of these disorders is important
      in order to correctly classify and institute appropriate therapy, recognizing
      that reduced immunosuppression or withdrawal of therapy may be necessary, rather
      than treating as a malignant lymphoma.

PMID- 23541275
TI  - Introduction to the series of reactive and abnormal lymphoid proliferations
      mimicking malignant lymphoma.

PMID- 23541276
TI  - Diffusion-weighted MR imaging of mucin-rich mucinous tubular and spindle cell
      carcinoma of the kidney: a case report.
AB  - Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare indolent subtype of
      renal cell carcinoma, which has variable magnetic resonance (MR) imaging features
      due to histomorphologic diversity. Diffusion-weighted MR imaging has shown its
      ability to differentiate benign and malignant renal neoplasms in some recent
      studies and can be a useful adjunct to routine MR sequences in ambiguous cases.
      We present a histopathology proven case of MTSCC highlighting the role of
      diffusion-weighted imaging in guiding the surgical management.

PMID- 23541277
TI  - Apparent diffusion coefficient and diffusion-weighted signal intensity of the
      interpeduncle region of the midbrain in adults: initial evaluation.
AB  - OBJECTIVE: The diffusion-weighted signal intensity (SI) of the interpeduncle
      region (IPR) of the midbrain has not been fully understood. This study was to
      evaluate the apparent diffusion coefficient (ADC) and SI of the IPR on axial
      diffusion-weighted imaging (DWI). METHODS: Axial brain DWI (4-mm slice thickness,
      no gap) was performed in 145 healthy subjects at 1.5T MR scanner. Correlations
      between the contrast-to-noise ratio (CNR) and ADC value in the IPR and age,
      gender were statistically analyzed. RESULTS: The CNR was significantly higher in
      the IPR than in the periaqueductal gray (PAG) (P<.001). The CNR of the IPR
      positively correlated with age (P=.032) but not with gender (P=.091). The ADC
      value was significantly lower in the IPR than in the PAG (P<.001). The ADC value
      of the IPR did not correlate with age (P=.522) or gender (P=.217). There was no
      correlation between the CNR and ADC value of the IPR (P=.622). CONCLUSIONS: The
      IPR usually shows high SI on DWI in healthy subjects, especially in older adults.
      DWI combined with the ADC maps would help to evaluate signal characteristics of
      the IPR.

PMID- 23541278
TI  - Comparison of CT and MRI findings in the differentiation of acute from chronic
      cholecystitis.
AB  - We compared individual computed tomography (CT) and MRI findings in
      differentiating acute from chronic cholecystitis. Thirty-seven patients
      undergoing both studies before cholecystectomy were included. Two radiologists
      (R1/R2) independently assessed all cases. For detecting acute cholecystitis, MRI
      showed better sensitivity (R1) using gallbladder wall thickening, accuracy (R1)
      and sensitivity (R1) using gallstones, sensitivity (R1 and R2) and accuracy (R2)
      using gallbladder wall hyperemia, accuracy (R1 and R2) using gallbladder wall
      defect, and accuracy (R2) using adjacent liver hyperemia (P=.004-.063). MRI also
      showed better specificity (R2) using pericholecystic fat stranding (P=.016).
      Overall, several findings showed better sensitivity and/or accuracy for acute
      cholecystitis on MRI than CT.

PMID- 23541279
TI  - A QM/MM study of the absorption spectrum of harmane in water solution and
      interacting with DNA: the crucial role of dynamic effects.
AB  - We present a time-dependent density functional theory computation of the
      absorption spectra of one beta-carboline system: the harmane molecule in its
      neutral and cationic forms. The spectra are computed in aqueous solution. The
      interaction of cationic harmane with DNA is also studied. In particular, the use
      of hybrid quantum mechanics/molecular mechanics methods is discussed, together
      with its coupling to a molecular dynamics strategy to take into account dynamic
      effects of the environment and the vibrational degrees of freedom of the
      chromophore. Different levels of treatment of the environment are addressed
      starting from purely mechanical embedding to electrostatic and polarizable
      embedding. We show that a static description of the spectrum based on equilibrium
      geometry only is unable to give a correct agreement with experimental results,
      and dynamic effects need to be taken into account. The presence of two stable
      noncovalent interaction modes between harmane and DNA is also presented, as well
      as the associated absorption spectrum of harmane cation.

PMID- 23541280
TI  - Adrenal venous sampling for primary hyperaldosteronism in patients with
      concurrent chronic kidney disease.
AB  - PURPOSE: To assess the risk of developing contrast-induced nephropathy (CIN) and
      to evaluate the technical success of adrenal venous sampling (AVS) in patients
      with chronic kidney disease (CKD). MATERIALS AND METHODS: AVS was performed in 25
      patients with primary hyperaldosteronism and concurrent CKD to distinguish
      between unilateral and bilateral adrenal disease. One of the 25 patients
      underwent repeat AVS, for a total of 26 samplings. All patients received a
      hydration protocol before and after the procedure. Acute kidney injury (AKI)
      (increase in creatinine of 0.5 mg/dL or>25% above baseline) and diagnostic yield
      were determined. RESULTS: CKD was stage III in 20 patients (80%), stage IV in 4
      patients (16%), and stage V in 1 patient (4%). Median contrast volume was 25 mL
      (range, 10-250 mL). Of 26 studies, 25 (96%) were diagnostic; the one
      nondiagnostic AVS was repeated with success. Despite their elevated risks, only 2
      of 25 patients (8%) developed AKI, and neither patient required treatment.
      CONCLUSIONS: AVS can be performed safely with a high degree of technical success
      and low risk of CIN in patients with primary hyperaldosteronism and concurrent
      advanced CKD.

PMID- 23541281
TI  - Objective and subjective assessment of physician labor and resource utilization
      in maintenance percutaneous transluminal angioplasty of nonthrombosed
      hemodialysis arteriovenous fistulas versus arteriovenous grafts.
AB  - PURPOSE: To complement prior studies that have shown that arteriovenous fistula
      (AVF) thrombectomies require more time and equipment than arteriovenous graft
      (AVG) thrombectomies by measuring work via established instruments to determine
      whether there is also a difference in maintenance percutaneous transluminal
      angioplasty (PTA) of nonthrombosed AVFs versus AVGs. MATERIALS AND METHODS: PTA
      procedures performed on a consecutive cohort of 42 patients with AVFs and 27
      patients with AVGs were prospectively compared. To quantify resource utilization,
      procedure time and disposable equipment were measured. Established instruments
      developed by the American Medical Association for Current Procedural Terminology
      code valuation were used to measure subjective "physician work," including mental
      effort and judgment, technical skill, physical effort, and psychological stress.
      These items were scored by 1 of 12 attending interventional radiology physicians
      performing the procedure. RESULTS: Mean PTA procedure time was 74 minutes (range,
      18-183 minutes) for AVFs and 71 minutes (range, 28-204 minutes) for AVGs;
      hemostasis time was 12 minutes for AVFs and 11 minutes for AVGs. There was no
      significant difference in equipment use between groups. "Physician work" for AVFs
      scored significantly higher in four categories (P<= .05). CONCLUSIONS: Using
      established subjective instruments, maintenance PTA of AVFs was scored as more
      cognitively, physically, and psychologically demanding than maintenance PTA of
      AVGs. However, there was no significant difference in resource utilization
      between maintenance PTA of AVFs versus AVGs, as has been previously shown with
      thrombectomy of thrombosed AVFs and AVGs.

PMID- 23541282
TI  - Catheter-based intraaccess blood flow measurement as a problem-solving tool in
      hemodialysis access intervention.
AB  - PURPOSE: To investigate retrospectively the use of catheter-based intraaccess
      blood flow measurements as an adjunct to physical examination and fistulography
      in hemodialysis access interventions. MATERIALS AND METHODS: Among 1,540 dialysis
      interventions performed at a single institution in a 2.5-year period, 104
      qualifying catheter-based flow measurements were made in 70 mature native fistula
      interventions in 55 patients and 34 graft interventions in 31 patients. The flow
      rate threshold prompting intervention was generally 600 mL/min, but some
      variation existed depending on the clinical setting. RESULTS: The most common
      indication for measurement of blood flow was to determine the hemodynamic
      significance of a fistula inflow stenosis (n = 25), of which only four had
      subsequent intervention. Other common indications included decision-making
      resulting in further angioplasty or stent implantation of noninflow lesions
      (fistulas, n = 10; grafts, n = 23) versus termination of the procedure (n = 23),
      problem-solving in cases in which there was no visible lesion to explain the
      clinical indicator of access failure (n = 17), evaluation for high-flow-related
      cardiac risk in aneurysmal fistulas (n = 13), suboptimal evaluation of the inflow
      (n = 8), and suboptimal physical examination (n = 6). Overall, flow measurements
      supported a decision to perform angioplasty (n = 11) or stent placement (n = 3)
      in 17% of fistula interventions and 35% of graft interventions. CONCLUSIONS: The
      major benefit of flow measurement was to support a decision to withhold further
      angioplasty or stent placement.

PMID- 23541283
TI  - A copper-catalyzed synthesis of 3-aroylindoles via a sp3 C-H bond activation
      followed by C-C and C-O bond formation.
AB  - An efficient Cu(I)-catalyzed synthesis of 3-aroylindoles has been achieved from o
      alkynylated N,N-dimethylamines via a sp(3) C-H bond activation alpha to the
      nitrogen atom followed by an intramolecular nucleophilic attack with the alkyne
      using an aqueous solution of tert-butyl hydroperoxide (TBHP) as the oxidant. In
      this tandem catalytic synthesis of 3-aroylindoles both C-C and C-O bonds are
      installed at the expense of two sp(3) C-H bond cleavages.

PMID- 23541284
TI  - Quo vadis TMAID? The new Editor-in-Chief widens the orbit.

PMID- 23541285
TI  - Symptomatic diaphragmatic hernia after pulmonary radiofrequency ablation.
AB  - Radiofrequency ablation (RF) is a relatively safe and reliable technique for the
      treatment of pulmonary metastases that has seen rapidly expanding use. Lesions
      situated near the diaphragm are difficult to treat by RF due to the risk of
      thermal injury to the diaphragm. Diaphragmatic perforation with progressive
      development of a diaphragmatic hernia is a rare but serious complication.
      Treatment is surgical. We present the first case reported in the literature of
      intestinal obstruction in a left diaphragmatic hernia that developed following RF
      treatment of a pulmonary metastasis.

PMID- 23541286
TI  - Structure-adaptive sparse denoising for diffusion-tensor MRI.
AB  - Diffusion tensor magnetic resonance imaging (DT-MRI) is becoming a prospective
      imaging technique in clinical applications because of its potential for in vivo
      and non-invasive characterization of tissue organization. However, the
      acquisition of diffusion-weighted images (DWIs) is often corrupted by noise and
      artifacts, and the intensity of diffusion-weighted signals is weaker than that of
      classical magnetic resonance signals. In this paper, we propose a new denoising
      method for DT-MRI, called structure-adaptive sparse denoising (SASD), which
      exploits self-similarity in DWIs. We define a similarity measure based on the
      local mean and on a modified structure-similarity index to find sets of similar
      patches that are arranged into three-dimensional arrays, and we propose a simple
      and efficient structure-adaptive window pursuit method to achieve sparse
      representation of these arrays. The noise component of the resulting structure
      adaptive arrays is attenuated by Wiener shrinkage in a transform domain defined
      by two-dimensional principal component decomposition and Haar transformation.
      Experiments on both synthetic and real cardiac DT-MRI data show that the proposed
      SASD algorithm outperforms state-of-the-art methods for denoising images with
      structural redundancy. Moreover, SASD achieves a good trade-off between image
      contrast and image smoothness, and our experiments on synthetic data demonstrate
      that it produces more accurate tensor fields from which biologically relevant
      metrics can then be computed.

PMID- 23541287
TI  - HIV/HBV coinfection: serological control and therapeutic strategies.
AB  - OBJECTIVES: The evolution and prognosis of patients co-infected by human
      immunodeficiency virus (HIV) and hepatitis B (HBV) is not well know. This study
      describes the treatment and serological, virological and biochemical and
      elastographic responses of HIV and HBV-coinfected patients. PATIENTS AND METHODS:
      A descriptive, retrospective study of all the HIV/HBV-coinfected patients seen in
      a specialized HIV department between 1 January 2007 and 30 November 2008 was
      performed. Virological and serological determinations of HIV and HBV infections
      as well as CD4 lymphocytes and transaminases prior to antiretroviral treatment
      and at the time of analysis were obtained. RESULTS: A total of 54 (5.4%) cases of
      HIV/HBV coinfection were identified. The median nadir and current CD4 were 179
      and 437 cells/L, respectively. There was undetectable RNA-HIV in 70%. There were
      52 patients (96.3%) who followed active drugs treatment against HBV. After
      treatment, 68.8% had HBeAg negative result, with 81.6% virologic response. The
      HBsAg became negative in 10.4%. ALT was normal in 75.5%. FibroScan((r)) was
      performed in 30 (55.6%) patients, yielding a median of 7.0kPa. CONCLUSIONS: The
      results obtained suggest a good serological, virological and biochemical control
      of HIV/HBV-coinfected patients with treatments recommended by clinical
      guidelines.

PMID- 23541289
TI  - Source apportionment of polycyclic aromatic hydrocarbons in surface sediment of
      mud areas in the East China Sea using diagnostic ratios and factor analysis.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and aliphatic hydrocarbons (AHs) have
      been quantified for surface sediments collected from the East China Sea (ECS).
      Our results showed that relatively high levels of PAHs and AHs occurred in both
      the inner and outer mud areas, while their concentrations at the control site
      were much lower. AHs for all samples were dominated by the unresolved complex
      mixture (UCM). Results from diagnostic ratios revealed that sedimentary PAHs were
      mainly originated from mixed combustion residues of biomass, coal, and petroleum.
      Combustion residues of petroleum and oil were responsible for the presence of
      high AHs concentrations. We also conducted factor analysis (FA) to further
      characterize the PAH and AH sources. Four factors were identified based on the
      loading of components and attributed to coal and wood combustion (Factor 1),
      traffic-related sources (Factor 2), petrogenic source (Factor 3) and natural gas
      combustion (Factor 4).

PMID- 23541290
TI  - Synthesis of large [2]rotaxanes. The relationship between the size of the
      blocking group and the stability of the rotaxane.
AB  - [2]Rotaxanes with large macrocyclic phenanthrolines were prepared by the template
      method, and the stability of the rotaxanes was examined. Compared to the
      tris(biphenyl)methyl group, the tris(4-cyclohexylbiphenyl)methyl group was a
      larger blocking group, and the rate of the dissociation of the components
      decreased significantly when the thermal stability of a rotaxane with a 41
      memebered ring was examined. We also succeeded in the synthesis of larger
      rotaxanes by the oxidative dimerization of alkynes with these bulky blocking
      groups, utilizing the catalytic activity of the macrocyclic phenanthroline-Cu
      complex.

PMID- 23541291
TI  - Concord grape juice reverses the age-related impairment in latent learning in
      rats.
AB  - OBJECTIVE: Two experiments were conducted to determine if dietary supplementation
      with Concord grape juice could reverse the latent learning impairment normally
      observed in middle-aged male rats. METHODS: Both experiments utilized the latent
      cue preference (LCP) task, in which water-replete rats sample water in one
      compartment of a three-compartment box, and are subsequently given a compartment
      preference test when water-deprived to determine if they remember the compartment
      cue previously associated with water. In the first experiment, 40 male Sprague
      Dawley rats (9, 10, 11, or 12 months old) were used to determine the age of onset
      of the impairment. In the second experiment, 24 male Sprague-Dawley rats (11
      months old) were given daily access (10 ml/day) to 50% Concord grape juice, 50%
      white grape juice, or a calorically-equivalent sugar solution daily for 5 weeks
      prior to training. RESULTS: The first experiment revealed that the latent
      learning impairment begins to manifest at 10 months of age in the male rats and
      is fully present at 11 months. The second experiment showed that rats that
      consumed the 50% Concord grape juice for 5 weeks beginning at 11 months of age
      showed intact latent learning in the LCP task, while rats that consumed the other
      two supplements showed the normal impairment on the LCP task. DISCUSSION: These
      results indicate that daily supplementation with Concord grape juice was able to
      reverse the latent learning impairment normally seen in middle-aged male rats.
      This reversal is most likely due to the presence of flavonoids in Concord grape
      juice.

PMID- 23541294
TI  - Endoscopic intranasal surgery for congenital nasolacrimal duct obstruction--a new
      approach.
AB  - OBJECTIVE: Congenital nasolacrimal duct obstruction can be treated with a
      spectrum of techniques, starting with conservative massage to more invasive
      dacryocystorhinostomy. There has been controversy regarding the optimal treatment
      procedure. We introduced a unique technique to treat congenital nasolacrimal duct
      obstruction and analyzed its success rate and complications. METHODS: In a
      retrospective study, we introduced the results of our technique. This technique
      consisted of endoscope guided inspection of the Hasner valve area, trial of
      irrigation, incision of the imperforate Hasner valve and irrigation again. If
      these maneuvers were not effective, more invasive procedure, probing under
      endoscopic control was done. RESULTS: 48 children (55 eyes) were included in the
      study. Complete improvement was achieved in 51/55 eyes (92.72% success rate). We
      did not encounter any early or late complication. CONCLUSIONS: The great majority
      of the congenital nasolacrimal duct obstruction stem from Hasner valve area
      pathologies. The endoscopic intervention of this area is very effective and safe
      way of treatment. This technique should be added to the armamentarium of the
      congenital nasolacrimal duct obstruction treatment.

PMID- 23541295
TI  - Investigating the mechanisms of cardiovascular and cerebrovascular regulation in
      orthostatic syncope through an information decomposition strategy.
AB  - Some previous evidence suggests that postural related syncope is associated with
      defective mechanisms of cerebrovascular (CB) and cardiovascular (CV) control. We
      characterized the information processing in short-term CB regulation, from the
      variability of mean cerebral blood flow velocity (CBFV) and mean arterial
      pressure (AP), and in CV regulation, from the variability of heart period (HP)
      and systolic AP (SAP), in ten young subjects developing orthostatic syncope in
      response to prolonged head-up tilt testing. We exploited a novel information
      theoretic approach that decomposes the information associated with a variability
      series into three amounts: the information stored in the series, the information
      transferred to the series from another series, and the information unexplained by
      the knowledge of both series. With this approach we were able to show that,
      compared with the first minutes after head-up tilt, in the period preceding the
      syncope event (i) the information stored in CBFV variability decreased
      significantly while the information transferred to CBFV from AP variability
      increased significantly; (ii) the information storage of HP was kept high but the
      information transferred to HP from SAP variability decreased significantly. These
      patterns of information processing suggest that presyncope occurs with a loss
      both of CB regulation, described by the reduced ability of CBFV of buffering AP
      fluctuations, and of CV regulation, described by the reduced baroreflex
      modulation from SAP to HP. We believe that the utilization of tools from the
      field of information dynamics may give an integrated view of the mechanisms of CB
      and CV regulation in normal and diseased states, and also provide a deeper
      understanding of findings revealed by more traditional techniques. 

PMID- 23541296
TI  - Information domain analysis of the spontaneous baroreflex during pharmacological
      challenges.
AB  - The information carried by heart period (HP) given systolic arterial pressure
      (SAP) changes was assessed to characterize spontaneous baroreflex (i.e. the
      relation linking SAP variability to HP variability): the larger the information
      carried by HP given SAP changes, the greater the unpredictability of HP given SAP
      variations, the smaller the strength of the causal coupling from SAP series to HP
      series. It was typified according to two parameters: i) the information carried
      by HP given SAP changes within the same heart cycle (i.e. 0-step-ahead
      information) describing immediate effects of SAP variations on HP; ii) the rate
      of increase of the information carried by HP given SAP changes as a function of
      the temporal distance, k, between the conditioning SAP pattern and future HP
      value (i.e. the rate of increase of k-step-ahead information with k) describing
      short-term effects of SAP modifications on HP. Both parameters were found under
      vagal control. Indeed, i) 0-step-ahead information suggested that HP and SAP
      variabilities were significantly coupled from SAP to HP at baseline and after the
      reduction of the inhibitory effect of sympathetic control on vagal influences
      performed through the administration of propranolol or clonidine; and ii) during
      vagal blockade induced by atropine or combined vagal and sympathetic blockade
      induced by the administration of propranolol after atropine k-step-ahead
      information reached a level incompatible with coupled HP and SAP dynamics
      regardless of k. In addition, it was found that the 0-step-ahead information at
      baseline and after propranolol and the rate of increase of k-step-ahead
      information with k at baseline could be exclusively explained in terms of linear
      HP-SAP interactions. Conversely, the same parameters after clonidine suggested
      the raise of nonlinear mechanisms probably unveiled by the central sympathetic
      blockade. Comparison with more traditional parameters describing the HP-SAP
      variability relation such as baroreflex sensitivity and squared HP-SAP coherence
      confirmed the complementary value of the proposed information domain analysis. 

PMID- 23541298
TI  - Preface: forum on aspects of inorganic chemistry related to nuclear energy.

PMID- 23541299
TI  - Protocol for Candrive II/Ozcandrive, a multicentre prospective older driver
      cohort study.
AB  - The Candrive II/Ozcandrive study, a multicentre prospective cohort study
      examining the predictive validity of tools for assessing fitness to drive, aims
      to develop an in-office screening tool that will help clinicians identify older
      drivers who may be unsafe to drive. This paper describes the study protocol. We
      are following a cohort of drivers aged >=70 years for up to 4 years. Starting in
      2009, 928 participants have been recruited in seven cities in four Canadian
      provinces, as well as 302 participants in two sites in Melbourne, Australia and
      Wellington, New Zealand. Participants underwent a comprehensive assessment at
      baseline and repeat the assessment yearly thereafter, as well as a brief follow
      up assessment at 4 and 8 months each year. A recording device is installed in
      participants' vehicles to assess driving patterns, and driving records are
      obtained from licensing authorities to determine the outcomes: at-fault crashes
      per kilometre driven and violations. To date, the protocol has been generally
      well adhered to, with 1230 participants, and barriers and challenges are being
      addressed, as necessary. The Candrive II/Ozcandrive study is unique owing to its
      size, duration, partnerships with Canadian, Australian and New Zealand
      stakeholders, and international research collaboration. 

PMID- 23541300
TI  - Publishing a DNP capstone: the where, what and how.

PMID- 23541297
TI  - Quantitative neurofibrillary tangle density and brain volumetric MRI analyses in
      Alzheimer's disease presenting as logopenic progressive aphasia.
AB  - Neurofibrillary tangles (NFTs) are one of the key histological lesions of
      Alzheimer's disease (AD) and are associated with brain atrophy. We assessed
      regional NFT density in 30 patients with AD, 10 of which presented as the
      logopenic variant of primary progressive aphasia (lvPPA) and 20 that presented as
      dementia of the Alzheimer's type (DAT). Regional grey matter volumes were
      measured using antemortem MRI. NFT density was significantly higher in left
      temporoparietal cortices in lvPPA compared to DAT, with no differences observed
      in hippocampus. There was a trend for the ratio of temporoparietal-to-hippocampal
      NFT density to be higher in lvPPA. The imaging findings mirrored the pathological
      findings, with smaller left temporoparietal volumes observed in lvPPA compared to
      DAT, and no differences observed in hippocampal volume. This study demonstrates
      that lvPPA is associated with a phenomenon of enhanced temporoparietal
      neurodegeneration, a finding that improves our understanding of the biological
      basis of lvPPA. 

PMID- 23541301
TI  - [Funding research in nephrology: the essential partnership between scientific
      societies and Kidney Foundation].

PMID- 23541302
TI  - [How parathyroid hormone (PTH) Does regulates calcium? Particulars of the patient
      with chronic kidney disease].

PMID- 23541304
TI  - Resveratrol is cidal to both classes of Haemophilus ducreyi.
AB  - Resveratrol, a polyphenolic phytoalexin, is produced by plants in response to
      infection and has antibacterial activity. Haemophilus ducreyi is a Gram-negative
      bacterium that is the causative agent of the sexually transmitted disease
      chancroid. This study employed minimum cidal concentration (MCC) assays to
      evaluate the potential of resveratrol as a microbicide against H. ducreyi. Five
      class I and four class II strains of H. ducreyi tested had MCCs <=500 MUg/mL.
      Resveratrol was also tested against Lactobacillus spp., part of the natural
      vaginal flora. Representative strains of Lactobacillus were co-cultured with H.
      ducreyi and 500 MUg/mL resveratrol; in all cases, Lactobacillus was recovered in
      greater numbers than H. ducreyi. These results show that resveratrol is not only
      bacteriostatic but is bactericidal to H. ducreyi, confirming the compound's
      potential for use as a topical microbicide to prevent chancroid.

PMID- 23541303
TI  - Initiation of buprenorphine during incarceration and retention in treatment upon
      release.
AB  - We report here on a feasibility study of initiating buprenorphine/naloxone prior
      to release from incarceration and linking participants to community treatment
      providers upon release. The study consisted of a small number of Rhode Island
      (RI) prisoners (N = 44) diagnosed with opioid dependence. The study design is a
      single arm, open-label pilot study with a 6-month follow up interview conducted
      in the community. However, a natural experiment arose during the study comparing
      pre-release initiation of buprenorphone/naloxone to initiation post-release. Time
      to post-release prescriber appointment (mean days) for initiation of treatment
      outside Rhode Island Department of Corrections (RIDOC) versus inside RIDOC was
      8.8 and 3.9, respectively (p = .1). Median post release treatment duration
      (weeks) for outside RIDOC versus inside RIDOC was 9 and 24, respectively (p =
      .007). We conclude that initiating buprenorphine/naloxone prior to release from
      incarceration may increase engagement and retention in community-based treatment.

PMID- 23541305
TI  - High-throughput screening for native autoantigen-autoantibody complexes using
      antibody microarrays.
AB  - We report on a novel, high-dimensional method to detect autoantibodies that are
      complexed with their natural autoantigens. Specifically, autoantibody-autoantigen
      complexes in serum or plasma are directly incubated onto a high-density antibody
      microarray. Detection of the bound autoantibody-antigen complex is made via
      fluorescently labeled antihuman immunoglobulin G or other immunoglobulin isotype
      secondary antibodies and quantification in a microarray scanner. Uncomplexed
      antibodies do not interfere with this assay. The whole process is very rapid and
      applicable for high-throughput screening without the need for production of
      proteins or immunoglobulin purification from the samples. Using these methods, we
      found that plasma from healthy individuals contains hundreds of autoantibodies
      complexed with cellular proteins. Thus, this highly sensitive, multiplex method
      is capable of discovering new autoantibody-antigen or circulating immune
      complexes, many of which will likely be useful for disease detection and
      characterization.

PMID- 23541306
TI  - Novel-structured electrospun TiO2/CuO composite nanofibers for high efficient
      photocatalytic cogeneration of clean water and energy from dye wastewater.
AB  - It is still a challenge to photocatalytically cogenerate clean water and energy
      from dye wastewater owing to the relatively low photocatalytic efficiency of
      photocatalysts. In this study, novel-structured TiO2/CuO composite nanofibers
      were successfully fabricated via facile electrospinning. For the first time, the
      TiO2/CuO composite nanofibers demonstrated multifunctional ability for concurrent
      photocatalytic organic degradation and H2 generation from dye wastewater. The
      enhanced photocatalytic activity of TiO2/CuO composite nanofibers was ascribed to
      its excellent synergy of physicochemical properties: 1) mesoporosity and large
      specific surface area for efficient substrate adsorption, mass transfer and light
      harvesting; 2) red-shift of the absorbance spectra for enhanced light
      utilization; 3) long nanofibrous structure for efficient charge transfer and ease
      of recovery, 4) TiO2/CuO heterojunctions which enhance the separation of
      electrons and holes and 5) presence of CuO which serve as co-catalyst for the H2
      production. The TiO2/CuO composite nanofibers also exhibited rapid settleability
      by gravity and uncompromised reusability. Thus, the as-synthesized TiO2/CuO
      composite nanofibers represent a promising candidate for highly efficient
      concurrent photocatalytic organic degradation and clean energy production from
      dye wastewater.

PMID- 23541307
TI  - The importance of laboratory water quality for studying initial bacterial
      adhesion during NF filtration processes.
AB  - Biofouling of nanofiltration (NF) and reverse osmosis (RO) membranes for water
      treatment has been the subject of increased research effort in recent years. A
      prerequisite for undertaking fundamental experimental investigation on NF and RO
      processes is a procedure called compaction. This involves an initial phase of
      clean water permeation at high pressures until a stable permeate flux is reached.
      However water quality used during the compaction process may vary from one
      laboratory to another. The aim of this study was to investigate the impact of
      laboratory water quality during compaction of NF membranes. A second objective
      was to investigate if the water quality used during compaction influences initial
      bacterial adhesion. Experiments were undertaken with NF 270 membranes at 15 bar
      for permeate volumes of 0.5 L, 2 L, and 5 L using MilliQ, deionized or tap water.
      Membrane autopsies were performed at each permeation point for membrane surface
      characterisation by contact angle measurements, profilometry, and scanning
      electron microscopy. The biological content of compacted membranes was assessed
      by direct epi-fluorescence observation following nucleic acid staining. The
      compacted membranes were also employed as substrata for monitoring the initial
      adhesion of Ps. fluorescens under dynamic flow conditions for 30 min at 5 min
      intervals. Compared to MilliQ water, membrane compaction using deionized and tap
      water led to decreases in permeate flux, increase in surface hydrophobicity and
      led to significant build-up of a homogeneous fouling layer composed of both
      living and dead organisms (>10(6) cells cm(-2)). Subsequent measurements of
      bacterial adhesion resulted in cell loadings of 0.2 * 10(5), 1.0 * 10(5) cells
      cm(-2) and 2.6 * 10(5) cells cm(-2) for deionized, tap water and MilliQ water,
      respectively. These differences in initial cell adhesion rates demonstrate that
      choice of laboratory water can significantly impact the results of bacterial
      adhesion on NF membranes. Standardized protocols are therefore needed for the
      fundamental studies of bacterial adhesion and biofouling formation on NF and RO
      membrane. This can be implemented by first employing pure water during all
      membrane compaction procedures and for the modelled feed solutions used in the
      experiment.

PMID- 23541308
TI  - Nucleation and growth kinetics of struvite crystallization.
AB  - Struvite crystallization technology is being widely applied in full-scale due to
      a surge in nutrient demand and phosphate price increases. Past investigations on
      struvite crystallization focused on process efficiency and thermodynamics, and
      less on kinetics, while mainly using fluidized bed type crystallizer. In this
      work, nucleation and growth kinetic data were measured using stirred vessel. The
      primary and secondary nucleation was measured in synthetic wastewater, and
      crystal growth in digested supernatant. The measured kinetic data was correlated
      with solution supersaturation. The dependence of growth rate on relative
      supersaturation in the digested was higher compared to synthetic wastewater. The
      crystal polymorph in synthetic wastewater and real wastewater was comparable.
      Products from the growth studies showed narrow size distribution and favorable
      separation characteristics. The secondary nucleation rate showed second order
      dependence on relative supersaturation. The nucleation induction time decreased
      with an increase in supersaturation ratio with a clear distinction between
      homogenous and heterogeneous primary nucleation.

PMID- 23541309
TI  - Ozonation of trimethoprim in aqueous solution: identification of reaction
      products and their toxicity.
AB  - This work aimed to better understand the ozonation process of a typical
      antibiotic pharmaceutical, trimethoprim in aqueous solution. The parent compound
      was almost completely degraded with ozone dose up to 3.5 mg/L with no
      mineralization. Twenty one degradation products were identified using an
      electrospray quadrupole time-of-flight mass spectrometer. Several ozonation
      pathways were proposed including hydroxylation, demethylation, carbonylation,
      deamination and methylene group cleavage. Two species of luminescent bacteria
      Photobacterium phosphoreum and Vibrio qinghaiensis were selected to assess the
      toxicity of ozonation products. For P. phosphoreum, higher level of toxicity was
      observed compared to the parent compound, but a negligible toxicity change was
      observed for V. qinghaiensis, indicating different modes of action for the same
      water sample. This was further confirmed by quantitative structure-active
      relationship analysis. This work proves the dominant role of ozone rather than
      hydroxyl radicals in the reaction and the potential risk after ozonation.

PMID- 23541310
TI  - Comprehensive care program for elderly patients over 65 years with hip fracture.
AB  - OBJECTIVES: To report the health outcomes of a multidisciplinary care program for
      patients over 65 years with hip fracture. PATIENTS AND METHODS: We have developed
      a care coordination model for the comprehensive care of hip fracture patients. It
      establishes what, who, when, how and where orthopedists, internists, family
      physicians, emergency, intensive care, physiotherapists, anesthetists, nurses and
      workers social intervene. All elderly patients over 65 years admitted with the
      diagnosis of hip fracture (years 2006 to 2010) were retrospectively evaluated.
      RESULTS: One thousand episodes of hip fracture, corresponding to 956 patients,
      were included. Mean age was 82 years and mean stay 6.7 days. This was reduced by
      1.14 days during the 5 years of the program. A total of 85.1% were operated on
      before 72 yours, and 91.2% during the program. Incidence of surgical site
      infection was 1.5%. In-hospital mortality was 4.5%, (24.2% at 12 months).
      Readmissions at one years was 14.9%. Independence for basic activity of daily
      living was achieved by 40% of the patients. CONCLUSIONS: This multidisciplinary
      care program for hip fracture patients is associated with positive health
      outcomes, with a high percentage of patients treated early (more than 90%),
      reduced mean stay (less than 7 days), incidence of surgical site infections,
      readmissions and inpatient mortality and at one year, as well as adequate
      functional recovery.

PMID- 23541313
TI  - Epithelial ovarian tumors and fertility drugs--are we asking the right questions?

PMID- 23541314
TI  - The two health disparities of uterine fibroids.

PMID- 23541315
TI  - Pain in the upper anterior-lateral part of the thigh in women affected by
      endometriosis: study of sensitive neuropathy.
AB  - OBJECTIVE: To assess whether pain in the anterior-lateral part of the thigh in
      women affected by endometriosis is due to femoral nerve invasion by endometriotic
      implants. DESIGN: Case-control study. SETTING: Hospital. PATIENT(S): We enrolled
      30 patients with endometriosis and leg pain in the anterior-lateral part of the
      thigh and 30 healthy women. INTERVENTION(S): Skin biopsy and neurologic
      examination for detection of neuropathy. MAIN OUTCOME MEASURE(S): Intraepidermal
      small fiber density reduction and positive neurologic examination agree with
      sensitive neuropathy. RESULT(S): Biopsy results showed no statistically
      significant difference between the case group and the control group. At
      neurologic examination nine patients in the study group (30%) showed positive
      results, none in the control group showed signs. These nine patients had reduced
      intraepidermal small fiber density, compared to the lower cutoff values of the
      control group, suggesting a sensitive neuropathy. CONCLUSION(S): When there is
      leg pain in women with endometriosis it is important to distinguish neuropathic
      from referred pain. Skin biopsy and neurologic examination should be introduced
      in the management of leg pain in endometriosis, due to their low invasiveness to
      diagnose a sensitive neuropathy. As a result early detection of nerve injury and
      planning for a prompt specific treatment would be possible.

PMID- 23541316
TI  - Role of angiotensin II and angiotensin-(1-7) in diabetes-induced oxidative DNA
      damage in the corpus cavernosum.
AB  - OBJECTIVE: To investigate diabetes mellitus (DM)-induced oxidative DNA damage,
      putative involvement of angiotensin (Ang) II, and possible modulatory effects of
      Ang-(1-7) in rat corpus cavernosum (CC). DESIGN: In vivo study. SETTING: Research
      laboratory. ANIMAL(S): Adult male Wistar rats. INTERVENTION(S): Streptozotocin
      induced diabetic rats received either captopril, losartan (both 300 mg/L in
      drinking water), or Ang-(1-7) (576 MUg/kg/d IP) for a 3-week period immediately
      before sacrifice at 6 weeks of DM. MAIN OUTCOME MEASURE(S): Histopathological
      changes in CC were examined in Masson's trichrome-stained tissue sections.
      Oxidative stress was evaluated by measuring total oxidant status and antioxidant
      status. The DNA damage was estimated by measuring 8-hydroxy-2'-deoxyguanosine by
      immunohistochemistry and ELISA. RESULT(S): The CC smooth muscle degeneration was
      observed in association with an increase in total oxidant status and a decrease
      in total antioxidant status in rats with DM. Oxidative DNA damage was
      significantly increased in both cytoplasm and nuclei of CC in DM. Treatment with
      captopril, losartan, or Ang-(1-7) inhibited these changes in rats with DM.
      CONCLUSION(S): The data indicate that Ang II signaling is involved in DM-induced
      structural changes and oxidative DNA damage in the CC and that modulation of the
      signaling by captopril, losartan, and Ang-(1-7) restores the effects of DM. Thus,
      Ang-(1-7)/MAS1 axis may be a novel therapeutic target for erectile dysfunction in
      DM.

PMID- 23541317
TI  - Antimullerian hormone, the assessment of the ovarian reserve, and the
      reproductive outcome of the young patient with cancer.
AB  - The accurate assessment of the ovarian reserve has long been a key goal in
      reproductive medicine. The recognition that serum antimullerian hormone provides
      an indirect measure of the ovarian reserve has led to its rapid adoption in
      assisted conception, and wide exploration of its potential across the
      reproductive lifespan from the neonate to the menopause. In this short review we
      discuss its relationship with the ovarian reserve in its varied meanings, and in
      various contexts. These include in childhood and adolescence, and in the
      assessment of the impact of cancer therapy on the female reproductive tract.
      These therapies can adversely impact all aspects of female reproduction,
      including hypothalamic, pituitary, and ovarian hormonal activity, and the ability
      of the uterus to support a successful pregnancy.

PMID- 23541318
TI  - A combination impression technique by Accu-Dent((r)) System broadly extends the
      surface area of primary casts.

PMID- 23541319
TI  - Distribution of radii of curvature of anterior and posterior best fit sphere in a
      normal population: the Tehran Eye Study.
AB  - PURPOSE: To determine the distribution and determinants of the radii of curvature
      of the anterior and posterior best fit spheres (ABFS and PBFS) of the cornea in a
      sample from the general normal population of Tehran. METHODS: A stratified random
      cluster sampling was used to select samples from the first 4 districts of Tehran
      proportionate to the population of each stratum. We examined the distribution of
      the ABFS and PBFS, as measured with the Orbscan II in different groups of age,
      sex, and refractive error, and determined their relationship with other variables
      by using both univariate and multiple regression analyses. Valid data was
      collected from 800 eyes, and analyses were done with data from 399 right eyes
      only. RESULTS: Mean ABFS and PBFS in the studied sample were 43.31+/-1.79D and
      52.67+/-3.04D, respectively. ABFS increased with age while PBFS showed no
      significant association; both showed significant inter-sex differences. In the
      multiple linear regression model, both ABFS and PBFS significantly correlated
      directly with age and average keratometry, and inversely with corneal diameter;
      PBFS correlated directly with anterior chamber depth as well. Mean PBFS/ABFS
      ratio was 1.22+/-0.05 which significantly decreased with age and was
      significantly higher in females. CONCLUSION: Knowledge of normal ranges of ABFS
      and PBFS and their determinants, including age, mean keratometry, and corneal
      diameter, as well as the choice of measurement device, is necessary for comparing
      information from different populations and interpreting results.

PMID- 23541321
TI  - Multiple breath nitrogen washout profiles in asthmatic patients: what do they
      mean clinically?

PMID- 23541320
TI  - Signal transducer and activator of transcription 1 (STAT1) gain-of-function
      mutations and disseminated coccidioidomycosis and histoplasmosis.
AB  - BACKGROUND: Impaired signaling in the IFN-gamma/IL-12 pathway causes
      susceptibility to severe disseminated infections with mycobacteria and dimorphic
      yeasts. Dominant gain-of-function mutations in signal transducer and activator of
      transcription 1 (STAT1) have been associated with chronic mucocutaneous
      candidiasis. OBJECTIVE: We sought to identify the molecular defect in patients
      with disseminated dimorphic yeast infections. METHODS: PBMCs, EBV-transformed B
      cells, and transfected U3A cell lines were studied for IFN-gamma/IL-12 pathway
      function. STAT1 was sequenced in probands and available relatives. Interferon
      induced STAT1 phosphorylation, transcriptional responses, protein-protein
      interactions, target gene activation, and function were investigated. RESULTS: We
      identified 5 patients with disseminated Coccidioides immitis or Histoplasma
      capsulatum with heterozygous missense mutations in the STAT1 coiled-coil or DNA
      binding domains. These are dominant gain-of-function mutations causing enhanced
      STAT1 phosphorylation, delayed dephosphorylation, enhanced DNA binding and
      transactivation, and enhanced interaction with protein inhibitor of activated
      STAT1. The mutations caused enhanced IFN-gamma-induced gene expression, but we
      found impaired responses to IFN-gamma restimulation. CONCLUSION: Gain-of-function
      mutations in STAT1 predispose to invasive, severe, disseminated dimorphic yeast
      infections, likely through aberrant regulation of IFN-gamma-mediated
      inflammation.

PMID- 23541323
TI  - Small-airways deposition of dornase alfa in children with asthma and persistent
      airway obstruction.

PMID- 23541322
TI  - Increased expression of factor XIII-A in patients with chronic rhinosinusitis
      with nasal polyps.
AB  - BACKGROUND: Profound edema or formation of a pseudocyst containing plasma
      proteins is a prominent characteristic of nasal polyps (NP). However, the
      mechanisms underlying NP retention of plasma proteins in the submucosa remain
      unclear. Recently, we reported that impairment of fibrinolysis causes excessive
      fibrin deposition in NP and this might be involved in the retention of plasma
      proteins. Although the coagulation cascade plays a critical role in fibrin clot
      formation at extravascular sites, the expression and role of coagulation factors
      in NP remain unclear. OBJECTIVE: The objective of this study was to investigate
      the expression of coagulation factors in patients with chronic rhinosinusitis
      (CRS). METHODS: Sinonasal tissues were collected from patients with CRS and
      control subjects. We assayed mRNA for factor XIII-A (FXIII-A) by using real-time
      PCR and measured FXIII-A protein by means of ELISA, immunohistochemistry, and
      immunofluorescence. RESULTS: FXIII-A mRNA levels were significantly increased in
      NP tissue from patients with CRS with NP (P < .001) compared with uncinate tissue
      from patients with CRS or control subjects. Similarly, FXIII-A protein levels
      were increased in NP. Immunofluorescence analysis revealed that FXIII-A
      expression in inflammatory cells and FXIII-A(+) cell numbers were significantly
      increased in NP. Most FXIII-A staining was observed within CD68(+)/CD163(+) M2
      macrophages in NP. Levels of FXIII-A correlated with markers of M2 macrophages,
      suggesting that M2 macrophages are major FXIIIA-producing cells in NP.
      CONCLUSION: Overproduction of FXIII-A by M2 macrophages might contribute to the
      excessive fibrin deposition in the submucosa of NP, which might contribute to the
      tissue remodeling and pathogenesis of CRS with NP.

PMID- 23541325
TI  - On sharing unique reagents.

PMID- 23541324
TI  - Genome-wide association study identifies TH1 pathway genes associated with lung
      function in asthmatic patients.
AB  - BACKGROUND: Recent meta-analyses of genome-wide association studies in general
      populations of European descent have identified 28 loci for lung function.
      OBJECTIVE: We sought to identify novel lung function loci specifically for asthma
      and to confirm lung function loci identified in general populations. METHODS:
      Genome-wide association studies of lung function (percent predicted FEV1
      [ppFEV1], percent predicted forced vital capacity, and FEV1/forced vital capacity
      ratio) were performed in 4 white populations of European descent (n = 1544),
      followed by meta-analyses. RESULTS: Seven of 28 previously identified lung
      function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323)
      identified in general populations were confirmed at single nucleotide
      polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and
      IRF2) associated with ppFEV1 (P < 10(-4)) belong to the TH1 or IL-12 cytokine
      family pathway. By using a linear additive model, these 4 TH1 pathway SNPs
      cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4
      populations (P = 3 * 10(-11)). Genetic scores of these 4 SNPs were associated
      with ppFEV1 values (P = 2 * 10(-7)) and the American Thoracic Society severe
      asthma classification (P = .005) in the Severe Asthma Research Program
      population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma
      susceptibility were not associated with lung function. CONCLUSION: Genes involved
      in airway structure/remodeling are associated with lung function in both general
      populations and asthmatic subjects. TH1 pathway genes involved in anti
      virus/bacterial infection and inflammation modify lung function in asthmatic
      subjects. Genes associated with lung function that might affect asthma severity
      are distinct from those genes associated with asthma susceptibility.

PMID- 23541326
TI  - T cells in asthma: influences of genetics, environment, and T-cell plasticity.
AB  - Asthma is classically considered the archetypal T(H)2 disease, with increased
      circulating IgE levels and eosinophilic inflammation being caused by increased
      levels of T(H)2-type cytokines. However, this paradigm has been challenged
      because of the realization that strategies designed to suppress T(H)2 function
      are not effective for all patients. The clinical phenotype of asthma is
      notoriously heterogeneous and is affected by genetic and environmental exposures
      in addition to interactions between airway structural cells, including epithelial
      cells, and the immune system, as well as contributions from cells other than
      T(H)2 cells. A combination of genetic and environmental factors is thought to
      influence whether inflammation resolves or progresses, and the pulmonary
      epithelium is increasingly recognized to play a key role in this process. This
      complex interplay has made it increasingly apparent that immune responses are
      tailored to the individual patient and determined by the weight of each
      influence, and thus the label of asthma as a T(H)2 disease is too conservative.
      Indeed, an important concept that needs to be addressed, both in animal models
      and clinically, is that of T-cell plasticity and how lymphocytic responses are
      determined by environmental influences.

PMID- 23541327
TI  - Incidence and associated premorbid diagnoses of patients with chronic
      rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent condition with
      underexplored risk factors. OBJECTIVES: We sought to determine CRS incidence and
      evaluate associations with a range of premorbid medical conditions for chronic
      rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with
      nasal polyps (CRSwNP) using real-world clinical practice data. METHODS:
      Electronic health records data from 446,480 Geisinger Clinic primary care
      patients were used for a retrospective longitudinal cohort study for data from
      2001-2010. By using logistic regression, newly diagnosed CRS cases between 2007
      and 2009 were compared with frequency-matched control subjects on premorbid
      factors in the immediate (0-6 months), intermediate (7-24 months), and entire
      observed timeframes before diagnosis. RESULTS: The average incidence of CRS was
      83 +/- 13 CRSwNP cases per 100,000 person-years and 1048 +/- 78 CRSsNP cases per
      100,000 person-years. Between 2007 and 2009, 595 patients with incident CRSwNP
      and 7523 patients with incident CRSsNP were identified and compared with 8118
      control subjects. Compared with control subjects and patients with CRSsNP,
      patients with CRSwNP were older and more likely to be male. Before diagnosis,
      patients with CRS had a higher prevalence of acute rhinosinusitis, allergic
      rhinitis, chronic rhinitis, asthma, gastroesophageal reflux disease,
      adenotonsillitis, sleep apnea, anxiety, and headaches (all P < .001). Patients
      with CRSsNP had a higher premorbid prevalence of infections of the upper and
      lower airway, skin/soft tissue, and urinary tract (all P < .001). In the
      immediate and intermediate timeframes analyzed, patients with CRS had more
      outpatient encounters and antibiotic prescriptions (P < .001), but guideline
      recommended diagnostic testing was performed in a minority of cases. CONCLUSIONS:
      Patients who are given a diagnosis of CRS have a higher premorbid prevalence of
      anxiety, headaches, gastroesophageal reflux disease, sleep apnea, and infections
      of the respiratory system and some nonrespiratory sites, which results in higher
      antibiotic, corticosteroid, and health care use. The use of guideline-recommended
      diagnostic testing for confirmation of CRS remains poor.

PMID- 23541328
TI  - Hydroxychloroquine preferentially induces apoptosis of CD45RO+ effector T cells
      by inhibiting autophagy: a possible mechanism for therapeutic modulation of T
      cells.

PMID- 23541329
TI  - Unilateral deafness: a unique model for the investigation of functional
      plasticity mechanisms in the human auditory cortex.

PMID- 23541330
TI  - Acute exposure to microgravity does not influence the H-reflex with or without
      whole body vibration and does not cause vibration-specific changes in muscular
      activity.
AB  - PURPOSE: Many potential countermeasures for muscle and bone loss caused by
      exposure to microgravity require an uncompromised stretch reflex system. This is
      especially true for whole body vibration (WBV), as the main source of the
      neuromuscular activity during WBV has been attributed to stretch reflexes. A
      priori, it cannot be assumed that reflexes and Ia afferent transmission in
      particular have the same characteristics in microgravity as in normal gravity
      (NG). Therefore, the purpose of the study was to compare Ia afferent transmission
      in microgravity and NG and to assess how microgravity affects muscle activity
      during WBV. METHODS: In 14 participants, electromyographic activity of four leg
      muscles as well as Hoffmann-reflexes were recorded during NG and microgravity
      induced by parabolic flights. RESULTS: The size of the Hoffmann-reflex was
      reduced during WBV, but did not differ during acute exposure to microgravity
      compared to NG. The influence of the gravity conditions on the electromyographic
      activity did not change depending on the vibration condition. CONCLUSIONS: As far
      as the electromyographic activity of the recorded leg muscles is concerned, the
      effect of WBV is the same in microgravity as in NG. Moreover, Ia afferent
      transmission does not seem to be affected by acute exposure to microgravity when
      subjects are loaded with body weight and postural sway is minimized.

PMID- 23541331
TI  - Carotid body removal for treatment of chronic systolic heart failure.
AB  - BACKGROUND: Augmented reflex response from peripheral chemoreceptors
      characterises chronic heart failure (CHF), contributes to autonomic imbalance and
      exercise intolerance and predicts poor outcome. METHODS AND RESULTS: We present a
      case of a 56-year-old male patient with ischaemic CHF, who underwent surgical,
      unilateral carotid body resection to reduce peripheral chemosensitivity. At 2
      month and 6-month follow-ups, we document a persistent decrease in peripheral
      chemosensitivity accompanied by an improvement in exercise capacity, sleep
      disordered breathing and quality of life. Autonomic balance was favourably
      affected as evidenced by improved heart rate variability and augmented cardiac
      baroreflex sensitivity. There were no procedure-related adverse events.
      CONCLUSIONS: Denervation of a carotid body may offer a clinical strategy to
      restore autonomic balance and improve morbidity in heart failure (NCT01653821).

PMID- 23541332
TI  - Acrylamide neurotoxicity.
AB  - Acrylamide, a food contaminant, belongs to a large class of structurally similar
      toxic chemicals, 'type-2 alkenes', to which humans are widely exposed. Besides,
      occupational exposure to acrylamide has received wide attention through the last
      decades. It is classified as a neurotoxin and there are three important
      hypothesis considering acrylamide neurotoxicity: inhibition of kinesin-based fast
      axonal transport, alteration of neurotransmitter levels, and direct inhibition of
      neurotransmission. While many researchers believe that exposure of humans to
      relatively low levels of acrylamide in the diet will not result in clinical
      neuropathy, some neurotoxicologists are concerned about the potential for its
      cumulative neurotoxicity. It has been shown in several studies that the same
      neurotoxic effects can be observed at low and high doses of acrylamide, with the
      low doses simply requiring longer exposures. This review is focused on the
      neurotoxicity of acrylamide and its possible outcomes. 

PMID- 23541333
TI  - Abnormal fusiform activation during emotional-face encoding assessed with
      functional magnetic resonance imaging.
AB  - This functional magnetic resonance imaging study shows that children and adults
      with bipolar disorder (BD), compared with healthy subjects, exhibit impaired
      memory for emotional faces and abnormal fusiform activation during encoding.
      Fusiform activation abnormalities in BD were correlated with mania severity and
      may therefore represent a trait and state BD biomarker.

PMID- 23541334
TI  - Different multivariate techniques for automated classification of MRI data in
      Alzheimer's disease and mild cognitive impairment.
AB  - Automated structural magnetic resonance imaging (MRI) processing pipelines and
      different multivariate techniques are gaining popularity for Alzheimer's disease
      (AD) research. We used four supervised learning methods to classify AD patients
      and controls (CTL) and to prospectively predict the conversion of mild cognitive
      impairment (MCI) to AD from baseline MRI data. A total of 345 participants from
      the AddNeuroMed cohort were included in this study; 116 AD patients, 119 MCI
      patients and 110 CTL individuals. High resolution sagittal 3D MP-RAGE datasets
      were acquired and MRI data were processed using FreeSurfer. We explored the
      classification ability of orthogonal projections to latent structures (OPLS),
      decision trees (Trees), artificial neural networks (ANN) and support vector
      machines (SVM). Applying 10-fold cross-validation demonstrated that SVM and OPLS
      were slightly superior to Trees and ANN, although not statistically significant
      for distinguishing between AD and CTL. The classification experiments resulted in
      up to 83% sensitivity and 87% specificity for the best techniques. For the
      prediction of conversion of MCI patients at baseline to AD at 1-year follow-up,
      we obtained an accuracy of up to 86%. The value of the multivariate models
      derived from the classification of AD vs. CTL was shown to be robust and
      efficient in the identification of MCI converters.

PMID- 23541335
TI  - Missing the target: matrix metalloproteinase antitargets in inflammation and
      cancer.
AB  - Matrix metalloproteinases (MMPs) are reputed to cause the inflammatory tissue
      destruction characterizing chronic inflammatory diseases and to degrade basement
      membrane collagen, thereby facilitating cancer cell metastasis. However,
      following the disappointing MMP drug cancer trials, recent studies using mouse
      models of disease coupled with high-throughput methods for substrate discovery
      have revealed surprising and unexpected new biological roles of MMPs in
      inflammatory diseases and cancer in vivo. Thus, MMPs modify signaling pathways
      and regulate the activity of whole families of cytokines of the immune response
      by precise proteolytic processing. By cleaving and inactivating cytokine-binding
      proteins and protease inhibitors, cytokine activities are unmasked and activities
      of diverse proteases are increased in an interconnected protease web. With new
      substrates come new roles, and 10 of 24 murine MMPs have antitumorigenic and anti
      inflammatory roles making them drug antitargets; that is, their beneficial
      actions should not be inhibited. Here, we examine whether the discovery that MMPs
      are drug antitargets for one disease might pave the way for their use for other
      indications or whether this is a serious threat to the development of MMP
      inhibitors.

PMID- 23541336
TI  - Managing blunt trauma in patients receiving dabigatran etexilate: case study and
      review of the literature.

PMID- 23541337
TI  - Developing your clinical question: the key to successful research.

PMID- 23541338
TI  - EAU guidelines on the treatment and follow-up of non-neurogenic male lower
      urinary tract symptoms including benign prostatic obstruction.
AB  - OBJECTIVE: To present a summary of the 2013 version of the European Association
      of Urology guidelines on the treatment and follow-up of male lower urinary tract
      symptoms (LUTS). EVIDENCE ACQUISITION: We conducted a literature search in
      computer databases for relevant articles published between 1966 and 31 October
      2012. The Oxford classification system (2001) was used to determine the level of
      evidence for each article and to assign the grade of recommendation for each
      treatment modality. EVIDENCE SYNTHESIS: Men with mild symptoms are suitable for
      watchful waiting. All men with bothersome LUTS should be offered lifestyle advice
      prior to or concurrent with any treatment. Men with bothersome moderate-to-severe
      LUTS quickly benefit from alpha1-blockers. Men with enlarged prostates,
      especially those >40ml, profit from 5alpha-reductase inhibitors (5-ARIs) that
      slowly reduce LUTS and the probability of urinary retention or the need for
      surgery. Antimuscarinics might be considered for patients who have predominant
      bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can
      quickly reduce LUTS to a similar extent as alpha1-blockers, and it also improves
      erectile dysfunction. Desmopressin can be used in men with nocturia due to
      nocturnal polyuria. Treatment with an alpha1-blocker and 5-ARI (in men with
      enlarged prostates) or antimuscarinics (with persistent storage symptoms)
      combines the positive effects of either drug class to achieve greater efficacy.
      Prostate surgery is indicated in men with absolute indications or drug treatment
      resistant LUTS due to benign prostatic obstruction. Transurethral resection of
      the prostate (TURP) is the current standard operation for men with prostates 30
      80ml, whereas open surgery or transurethral holmium laser enucleation is
      appropriate for men with prostates >80ml. Alternatives for monopolar TURP include
      bipolar TURP and transurethral incision of the prostate (for glands <30ml) and
      laser treatments. Transurethral microwave therapy and transurethral needle
      ablation are effective minimally invasive treatments with higher retreatment
      rates compared with TURP. Prostate stents are an alternative to catheterisation
      for men unfit for surgery. Ethanol or botulinum toxin injections into the
      prostate are still experimental. CONCLUSIONS: These symptom-oriented guidelines
      provide practical guidance for the management of men experiencing LUTS. The full
      version is available online (www.uroweb.org/gls/pdf/12_Male_LUTS.pdf).

PMID- 23541339
TI  - dUTPases, the unexplored family of signalling molecules.
AB  - Deciphering the molecular mechanisms that control relevant cellular processes is
      of utmost importance to understand how viruses, prokaryotic and eukaryotic cells
      work. The diversity of living organisms suggests that there are novel regulators
      still to be discovered, which may uncover new regulatory paradigms. dUTPases
      (Duts) are assumed to be ubiquitous enzymes regulating cellular dUTP levels to
      prevent misincorporation of uracil into DNA. Recently however, Duts have been
      involved in the control of several relevant cellular processes, including
      transfer of mobile genetic elements, regulation of the immune system,
      autoimmunity or apoptosis, suggesting that they perform regulatory functions.
      This review aims at investigating the unexplored impact of Duts as novel
      signalling molecules.

PMID- 23541340
TI  - Perrault syndrome is caused by recessive mutations in CLPP, encoding a
      mitochondrial ATP-dependent chambered protease.
AB  - Perrault syndrome is a genetically and clinically heterogeneous autosomal
      recessive condition characterized by sensorineural hearing loss and ovarian
      failure. By a combination of linkage analysis, homozygosity mapping, and exome
      sequencing in three families, we identified mutations in CLPP as the likely cause
      of this phenotype. In each family, affected individuals were homozygous for a
      different pathogenic CLPP allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser),
      or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G. CLPP, a
      component of a mitochondrial ATP-dependent proteolytic complex, is a highly
      conserved endopeptidase encoded by CLPP and forms an element of the
      evolutionarily ancient mitochondrial unfolded-protein response (UPR(mt)) stress
      signaling pathway. Crystal-structure modeling suggests that both substitutions
      would alter the structure of the CLPP barrel chamber that captures unfolded
      proteins and exposes them to proteolysis. Together with the previous
      identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA
      synthetase, mutations in CLPP expose dysfunction of mitochondrial protein
      homeostasis as a cause of Perrault syndrome.

PMID- 23541341
TI  - The benefits of using genetic information to design prevention trials.
AB  - Clinical trials for preventative therapies are complex and costly endeavors
      focused on individuals likely to develop disease in a short time frame,
      randomizing them to treatment groups, and following them over time. In such
      trials, statistical power is governed by the rate of disease events in each group
      and cost is determined by randomization, treatment, and follow-up. Strategies
      that increase the rate of disease events by enrolling individuals with high risk
      of disease can significantly reduce study size, duration, and cost. Comprehensive
      study of common, complex diseases has resulted in a growing list of robustly
      associated genetic markers. Here, we evaluate the utility--in terms of trial
      size, duration, and cost--of enriching prevention trial samples by combining
      clinical information with genetic risk scores to identify individuals at greater
      risk of disease. We also describe a framework for utilizing genetic risk scores
      in these trials and evaluating the associated cost and time savings. With type 1
      diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), and advanced
      age-related macular degeneration (AMD) as examples, we illustrate the potential
      and limitations of using genetic data for prevention trial design. We illustrate
      settings where incorporating genetic information could reduce trial cost or
      duration considerably, as well as settings where potential savings are
      negligible. Results are strongly dependent on the genetic architecture of the
      disease, but we also show that these benefits should increase as the list of
      robustly associated markers for each disease grows and as large samples of
      genotyped individuals become available.

PMID- 23541342
TI  - Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to
      premature ovarian failure and hearing loss in Perrault syndrome.
AB  - The genetic causes of premature ovarian failure (POF) are highly heterogeneous,
      and causative mutations have been identified in more than ten genes so far. In
      two families affected by POF accompanied by hearing loss (together, these
      symptoms compose Perrault syndrome), exome sequencing revealed mutations in
      LARS2, encoding mitochondrial leucyl-tRNA synthetase: homozygous c.1565C>A
      (p.Thr522Asn) in a consanguineous Palestinian family and compound heterozygous
      c.1077delT and c.1886C>T (p.Thr629Met) in a nonconsanguineous Slovenian family.
      LARS2 c.1077delT leads to a frameshift at codon 360 of the 901 residue protein.
      LARS2 p.Thr522Asn occurs in the LARS2 catalytic domain at a site conserved from
      bacteria through mammals. LARS2 p.Thr629Met occurs in the LARS2 leucine-specific
      domain, which is adjacent to a catalytic loop critical in all species but for
      which primary sequence is not well conserved. A recently developed method of
      detecting remote homologies revealed threonine at this site in consensus
      sequences derived from multiple-species alignments seeded by human and E. coli
      residues at this region. Yeast complementation indicated that LARS2 c.1077delT is
      nonfunctional and that LARS2 p.Thr522Asn is partially functional. LARS2
      p.Thr629Met was functional in this assay but might be insufficient as a
      heterozygote with the fully nonfunctional LARS2 c.1077delT allele. A known C.
      elegans strain with the protein-truncating alteration LARS-2 p.Trp247Ter was
      confirmed to be sterile. After HARS2, LARS2 is the second gene encoding
      mitochondrial tRNA synthetase to be found to harbor mutations leading to Perrault
      syndrome, further supporting a critical role for mitochondria in the maintenance
      of ovarian function and hearing.

PMID- 23541343
TI  - Complete haplotype sequence of the human immunoglobulin heavy-chain variable,
      diversity, and joining genes and characterization of allelic and copy-number
      variation.
AB  - The immunoglobulin heavy-chain locus (IGH) encodes variable (IGHV), diversity
      (IGHD), joining (IGHJ), and constant (IGHC) genes and is responsible for antibody
      heavy-chain biosynthesis, which is vital to the adaptive immune response.
      Programmed V-(D)-J somatic rearrangement and the complex duplicated nature of the
      locus have impeded attempts to reconcile its genomic organization based on
      traditional B-lymphocyte derived genetic material. As a result, sequence
      descriptions of germline variation within IGHV are lacking, haplotype inference
      using traditional linkage disequilibrium methods has been difficult, and the
      human genome reference assembly is missing several expressed IGHV genes. By using
      a hydatidiform mole BAC clone resource, we present the most complete haplotype of
      IGHV, IGHD, and IGHJ gene regions derived from a single chromosome, representing
      an alternate assembly of ~1 Mbp of high-quality finished sequence. From this we
      add 101 kbp of previously uncharacterized sequence, including functional IGHV
      genes, and characterize four large germline copy-number variants (CNVs). In
      addition to this germline reference, we identify and characterize eight CNV
      containing haplotypes from a panel of nine diploid genomes of diverse ethnic
      origin, discovering previously unmapped IGHV genes and an additional 121 kbp of
      insertion sequence. We genotype four of these CNVs by using PCR in 425
      individuals from nine human populations. We find that all four are highly
      polymorphic and show considerable evidence of stratification (Fst = 0.3-0.5),
      with the greatest differences observed between African and Asian populations.
      These CNVs exhibit weak linkage disequilibrium with SNPs from two commercial
      arrays in most of the populations tested.

PMID- 23541345
TI  - Dimensional anxiety scales for DSM-5: sensitivity to clinical severity.
AB  - PURPOSE: Psychometric properties and clinical sensitivity of brief self-rated
      dimensional scales to supplement categorical diagnoses of anxiety disorders in
      the DSM-5 were recently demonstrated in a German treatment seeking sample of
      adults. The present study aims to demonstrate sensitivity of these scales to
      clinical severity levels. METHODS: The dimensional scales were administered to
      102 adults at a university outpatient clinic for psychotherapy. Diagnostic status
      was assessed using the Munich-Composite International Diagnostic Interview. To
      establish a wide range of clinical severity, we considered subthreshold (n=83)
      and threshold anxiety disorders (n=49, including Social Phobia, Specific Phobia,
      Agoraphobia, Panic Disorder, and Generalized Anxiety Disorder). RESULTS:
      Individuals with either subthreshold or threshold anxiety disorder scored higher
      on all dimensional scales relative to individuals without anxiety. In addition,
      individuals with a threshold anxiety disorder scored higher on the dimensional
      scales than individuals with a subthreshold anxiety disorder (except for specific
      phobia). Disorder-related impairment ratings, global functioning assessments and
      number of panic attacks were associated with higher scores on dimensional scales.
      Findings were largely unaffected by the number of anxiety disorders and comorbid
      depressive disorders. CONCLUSION: The self-rated dimensional anxiety scales
      demonstrated sensitivity to clinical severity, and a cut-off based on additional
      assessment of impairment and distress may assist in the discrimination between
      subthreshold and threshold anxiety disorders. Findings suggest further research
      in various populations to test the utility of the scales for use in DSM-5.

PMID- 23541344
TI  - Mutations in KCTD1 cause scalp-ear-nipple syndrome.
AB  - Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder
      characterized by cutis aplasia of the scalp; minor anomalies of the external
      ears, digits, and nails; and malformations of the breast. We used linkage
      analysis and exome sequencing of a multiplex family affected by SEN syndrome to
      identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations
      that cause SEN syndrome. Evaluation of a total of ten families affected by SEN
      syndrome revealed KCTD1 missense mutations in each family tested. All of the
      mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac,
      tram track, and broad complex (BTB) domain that is required for transcriptional
      repressor activity. KCTD1 inhibits the transactivation of the transcription
      factor AP-2alpha (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis
      aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a
      potential overlap in the pathogenesis of SEN syndrome and BOFS. The
      identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB
      domain-containing transcriptional repressor during ectodermal development.

PMID- 23541356
TI  - Perivascular epithelioid cell tumor: an unusual pancreatic mass diagnosed by EUS
      FNA.

PMID- 23541357
TI  - Cyclic siloxanes in air, including identification of high levels in Chicago and
      distinct diurnal variation.
AB  - The organosilicon compounds octamethylcyclotetrasiloxane (D4),
      decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) are
      high production volume chemicals that are widely used in household goods and
      personal care products. Due to their prevalence and chemical characteristics,
      cyclic siloxanes are being assessed as possible persistent organic pollutants.
      D4, D5, and D6 were measured in indoor and outdoor air to quantify and compare
      siloxane concentrations and compound ratios depending on location type. Indoor
      air samples had a median concentration of 2200 ng m(-3) for the sum of D4, D5,
      and D6. Outdoor sampling locations included downtown Chicago, Cedar Rapids, IA,
      and West Branch, IA, and had median sum siloxane levels of 280, 73, and 29 ng m(
      3) respectively. A diurnal trend is apparent in the samples taken in downtown
      Chicago. Nighttime samples had a median 2.7 times higher on average than daytime
      samples, which is due, in part, to the fluctuations of the planetary boundary
      layer. D5 was the dominant siloxane in both indoor and outdoor air. Ratios of D5
      to D4 averaged 91 and 3.2 for indoor and outdoor air respectively.

PMID- 23541358
TI  - Effects of landuse and precipitation on pesticides and water quality in playa
      lakes of the southern high plains.
AB  - The 25000 playa wetlands within the Southern High Plains (SHP) of the United
      States of America (USA) are the dominant hydrogeomorphic feature in the region,
      providing habitat for numerous plants and wildlife. The SHP are among the most
      intensively cultivated regions; there are concerns over the degradation and/or
      loss of playa wetland habitat. We examined water quality in playa wetlands
      surrounded by both grassland and agriculture and measured water concentrations of
      pesticides used on cotton (acephate, trifluralin, malathion, pendimethalin,
      tribufos, bifenthrin, lambda-cyhalothrin, acetamiprid, and thiamethoxam), the
      dominant crop in the SHP. Pesticides used on cotton were detected in water
      samples collected from all playas. Precipitation events and the amount of
      cultivation were related to pesticide concentrations in sediment and water. Our
      results show that pesticide concentrations were related in some circumstances to
      time, precipitation, and tilled-index for some but not all pesticides. We further
      compared measured pesticide concentrations in playas to toxicity benchmarks used
      by the US EPA in pesticide ecological risk assessments to obtain some insight
      into the potential for ecological effects. For all pesticides in water, the
      maximum measured concentrations exceeded at least one toxicity benchmark, while
      median concentrations did not exceed any benchmarks. This analysis indicates that
      there is a potential for adverse effects of pesticides to aquatic organisms.

PMID- 23541359
TI  - Electrochemical degradation of the antibiotic sulfachloropyridazine by hydroxyl
      radicals generated at a BDD anode.
AB  - The treatment of aqueous solutions of the antibiotic sulfachloropyridazine (SCP)
      was carried out at the natural pH of the solution (pH 4.5) with hydroxyl radicals
      (OH) generated at a BDD anode surface by electro-oxidation using an undivided
      electrochemical cell equipped with a three-dimensional carbon-felt cathode.
      Hydroxyl radicals are powerful oxidants and react with the antibiotic leading to
      its overall mineralization. The kinetic study showed that oxidative degradation
      of SCP follows pseudo first-order reaction kinetics, with a relatively short
      degradation time. The degree of mineralization of SCP solutions increased with
      the applied current, being higher than 95% after 8 h of electrolysis at 350 mA or
      higher current. To determine the degradation pathway upon the action of hydroxyl
      radicals, the cyclic and aliphatic by-products, as well as the released inorganic
      ions, were identified and quantified over electrolysis time. The values of the
      rate constants of reactions between OH and the SCP and its intermediates were
      determined by the competition kinetics method using p-hydroxybenzoic acid. The
      absolute rate constant for the OH-mediated degradation of SCP was found to be
      1.92 * 10(9)M(-1)s(-1). Toxicity assessment by the Microtox method during the
      electro-oxidation of SCP solutions revealed the formation of compounds that can
      be more toxic than the parent molecule, but the overall results confirm the
      effectiveness of this electrochemical process for the removal of the antibiotic
      SCP and its by-products from aqueous media.

PMID- 23541360
TI  - Influence of soil type and environmental conditions on ZnO, TiO(2) and Ni
      nanoparticles phytotoxicity.
AB  - Intensive development of nanotechnology will result in releasing nanoparticles
      (NPs) to the environment including soil. The objective of the study was the
      evaluation of phytotoxicity of inorganic nanoparticles and their bulk
      counterparts (ZnO, TiO(2) and Ni) in various soils using Phytotoxkit FTM method.
      The estimation of toxicity was conducted with relation to Lepidium sativum. The
      toxicity of NPs was also estimated in relation to contact time between NPs and
      soil, effect of light and temperature and NPs-NPs interactions. In all tested
      variants no effect of NPs on seed germination was observed. NPs displayed varied
      effect on inhibition of plant root growth in relation to soil type. Only in the
      case of ZnO nanoparticles and their bulk counterparts a dose-effect relationship
      was observed. That relationship, however, was observed only in OECD soil. In a
      majority of cases, aging and increase of temperature caused a reduction of
      toxicity of NPs, while light conditions increased the toxic effect of NPs. The
      effect of the NPs interaction: ZnO with TiO(2) or Ni had an antagonistic
      character, that was manifested in a reduction of the toxicity of ZnO.

PMID- 23541361
TI  - Women's views about the importance of education in preparation for childbirth.
AB  - BACKGROUND: This paper reports original research that embraces childbearing
      women's views about the importance of education in preparation for childbirth. A
      survey was carried out using the Birth Satisfaction Scale developed by Hollins
      Martin and Fleming (2011). All of the items in the questionnaire include a space
      where the women can add their own comments to allow them to document what is
      important to them. This paper reports the analysis of this qualitative data.
      METHODS: The qualitative data collected in the survey was analysed using Braun
      and Clarke's (2006) method for undertaking a thematic analysis. PARTICIPANTS:
      Participants were a convenience sample of postnatal women from a maternity unit
      in the West of Scotland (UK) (n = 228) who had an uncomplicated pregnancy at term
      (37-42 weeks). Those with a medical diagnosis, poor obstetric history,
      prematurity (<37 weeks), postmaturity (>42 weeks), younger than (<16) and over
      (>50) of age, had a history of stillbirth, perinatal or neonatal death were
      excluded from participating in the study. RESULTS: Three themes emerged from the
      data: 'Better to be prepared', 'Prepared through previous experience' and 'In
      labour nothing goes to plan'. CONCLUSION: The participants in this study were
      variable in their reports about the importance of education in preparation for
      childbirth, with some clearly presenting a perception of no need. For the
      midwife, importance lies in providing women with educational opportunities and
      choice and control in relation to uptake. RECOMMENDATIONS: Women may perceive
      more value in education when they evaluate it as critical to their outcomes. For
      example, providing information about: (a) how to identify risk factors before and
      after birth, (b) strategies that can work towards improving maternal and fetal
      health, (c) how to improve fetal growth and wellbeing, (d) how to improve
      nutritional and dietary status, (e) optimising pregnancy outcomes. In relation to
      delivery of education, midwives require to make purpose and links clear.

PMID- 23541362
TI  - Cardiopulmonary bypass during a second-lung implantation improves postoperative
      oxygenation after sequential double-lung transplantation.
AB  - OBJECTIVES: During sequential double-lung transplantation (DLT), the newly
      implanted first lung receives the entire cardiac output during the implantation
      of the second one. This may be responsible for the increased hydrostatic pressure
      that causes severe interstitial and alveolar edema that can lead to allograft
      dysfunction. The authors tested the hypothesis that CPB started after first graft
      implantation and before second recipient lung removal should improve post
      transplantation oxygenation and clinical outcomes. DESIGN: Observational during 2
      consecutive 1-year periods. SETTING: University hospital. PARTICIPANTS: Nine
      consecutive patients undergoing sequential DLT with CPB started after first graft
      implantation and before second recipient lung removal were compared to controls,
      who were 10 consecutive patients who underwent sequential DLT but without CPB the
      year before. MEASUREMENTS AND MAIN RESULTS: Oxygenation after transplantation was
      assessed. The use of CPB during the implantation of the second lung was
      associated with an increased mean postoperative ratio of PaO2 to the fraction of
      inspired oxygen at 1 hour (363+/-51 v 240+/-113, p = 0.01) and 6 hours (430+/-111
      v 280+/-103, p = 0.03). The mean duration of CPB was 111+/-19 min. The occurrence
      of primary graft dysfunction and the need for extracorporeal membrane oxygenation
      tended to be lower, but did not reach significance. Similarly, mortality rate was
      comparable between both groups, as was the rate of blood transfusions.
      CONCLUSIONS: The authors' results suggest that the use of CPB started after first
      graft implantation and before second recipient lung removal appears to benefit
      oxygenation and reduces the occurrence of severe pulmonary edema in the first
      transplanted lung.

PMID- 23541363
TI  - Radiation induces aerobic glycolysis through reactive oxygen species.
AB  - BACKGROUND AND PURPOSE: Although radiation induced reoxygenation has been thought
      to increase radiosensitivity, we have shown that its associated oxidative stress
      can have radioprotective effects, including stabilization of the transcription
      factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the
      glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to
      promote treatment resistance. Thus, we hypothesized that reoxygenation after
      radiation would increase glycolysis. We previously showed that blockade of
      oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation
      can downregulate HIF-1 activity. Here we tested whether concurrent use of this
      drug with radiotherapy would reduce the switch to a glycolytic phenotype.
      MATERIALS AND METHODS: 40 mice with skin fold window chambers implanted with 4T1
      mammary carcinomas were randomized into (1) no treatment, (2) radiation alone,
      (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were
      imaged on the ninth day following tumor implantation (30 h following radiation
      treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz
      2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was
      measured by using hyperspectral imaging to quantify oxygenation state. RESULTS:
      Mice treated with radiation showed significantly higher 2-NBDG fluorescence
      compared to controls (p=0.007). Hemoglobin saturation analysis demonstrated
      reoxygenation following radiation, coinciding with the observed increase in
      glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a
      significant reduction in 2-NBDG fluorescence compared to effects seen after
      radiation alone, while having no effect on reoxygenation. CONCLUSIONS: Radiation
      induces an increase in tumor glucose demand approximately 30 h following therapy
      during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic
      glycolysis when used concurrently with radiation, without preventing
      reoxygenation.

PMID- 23541364
TI  - The use of fused PET/CT images for patient selection and radical radiotherapy
      target volume definition in patients with non-small cell lung cancer: results of
      a prospective study with mature survival data.
AB  - BACKGROUND AND PURPOSE: This prospective study investigated the impact of
      radiotherapy (RT)-planning FDG-PET/CT on management of non-small cell lung cancer
      (NSCLC). MATERIALS AND METHODS: Patients still eligible for radical RT after
      conventional staging underwent RT-planning PET/CT and, if disease was still
      treatable to 60 Gy, they entered our planning study, where visually-contoured
      tumour volumes derived with and without PET information were compared. If PET/CT
      detected advanced disease, palliative therapy was given. Overall survival (OS)
      for palliative and curative patients was compared. RESULTS: Of 76 eligible
      patients, only 50 (66%) received radical chemoRT after PET/CT while 26 (34%)
      received palliative therapies because PET/CT detected advanced disease. Without
      PET, FDG-avid tumour would reside outside the planning target volume (PTV) in 36%
      of radical cases and in 25% <90% of the PTV would have received >95% prescribed
      dose. OS for all patients was 56.8% and 24.9% at 1 and 4 years, respectively. OS
      for patients given chemoRT was 77.5% and 35.6% at 1 and 4 years, respectively and
      was 32% for stage IIIA patients at 4 years. OS for patients treated palliatively
      was inferior (P<0.001); 16.3% and 4.1% at 1 and 4 years, respectively.
      CONCLUSIONS: Planning PET/CT frequently changed management and was associated
      with excellent survival. Survival data from this study were presented in part at
      the 2011 World Lung Cancer Conference, Amsterdam and planning data at the 2010
      Annual Scientific Meeting of the American Society for Therapeutic Radiology and
      Oncology, Chicago.

PMID- 23541365
TI  - Cloning and characterization of a novel cry8Ab1 gene from Bacillus thuringiensis
      strain B-JJX with specific toxicity to scarabaeid (Coleoptera: Scarabaeidae)
      larvae.
AB  - Isolation of Bacillus thuringiensis (Bt) strain or its cry gene encoding
      insecticidal crystal protein (ICP) with specific toxicity is of great importance
      to biological control of insect pests. In this study, by screening 66 strains of
      Bt isolated from soil samples collected in Shandong Province, China, a new cry8
      type gene from Bt strain B-JJX was identified via PCR-RFLP method. This novel
      gene, cry8Ab1, was cloned from the Bt strain B-JJX and expressed in an
      acrystalliferous mutant strain HD-73(-). The open reading frame of the cry8Ab1
      gene consists of 3543bp with a G+C content of 37.99% and encodes a protein of
      1180 amino acids with a putative MW of 133.3kDa which was confirmed by SDS-PAGE
      analysis. The Cry8Ab1 protein was expressed and released as spherical parasporal
      crystals from Bt acrystalliferous mutant strain HD-73(-) along with the presence
      of spores. In bioassays, this protein was toxic to 3-day-old larvae of the
      scarabaeid pests, Holotrichia oblita and H. parallela, with an LC50 of 5.72 and
      2.00MUgtoxing(-1)soil, respectively. The results are in accordance with the
      insecticidal activities of the original Bt strain B-JJX, which had an LC50 of
      1.72 and 0.96MUgtoxing(-1)soil against H. oblita and H. parallela, respectively. 

PMID- 23541366
TI  - Natural transformation as a mechanism of horizontal gene transfer among
      environmental Aeromonas species.
AB  - Aeromonas species are common inhabitants of aquatic environments and relevant as
      human pathogens. Their potential as pathogens may be related in part to lateral
      transfer of genes associated with toxin production, biofilm formation, antibiotic
      resistance, and other virulence determinants. Natural transformation has not been
      characterized in aeromonads. DNA from wild-type, prototrophic strains that had
      been isolated from environmental sources was used as donor DNA in transformation
      assays with auxotrophs as the recipients. Competence was induced in 20% nutrient
      broth during the stationary phase of growth. Optimal transformation assay
      conditions for one chosen isolate were in Tris buffer with magnesium or calcium,
      pH 5-8, and a saturating concentration of 0.5 MUg of DNA per assay (3.3 ng of DNA
      MUl-1) at 30 degrees C. Sodium was also required and could not be replaced with
      ammonium, potassium, or lithium. The maximal transformation frequency observed
      was 1.95 * 10-3 transformants (recipient cell)-1. A survey of environmental
      Aeromonas auxotrophic recipients (n=37), assayed with donor DNA from other wild
      type environmental aeromonads under optimal assay conditions, demonstrated that
      73% were able to act as recipients, and 100% were able to act as donors to at
      least some other aeromonads. Three different transformation groups were
      identified based on each isolates' ability to transform other strains with its
      DNA. The transformation groups roughly corresponded to phylogenetic groups. These
      results demonstrate that natural transformation is a general property of
      Aeromonas environmental isolates with implications for the genetic structures of
      coincident Aeromonas populations.

PMID- 23541367
TI  - Oxidized arachidonic acid and hexanal enhance mouse taste perception of
      monosodium glutamate.
AB  - OBJECTIVE: Little is known about whether mammals use gustatory sense to detect
      compounds produced from oxidized oil as a taste or only use olfactory sense to
      detect the compounds as aroma. The present study examined the effects of oxidized
      arachidonic acid (AA) ethyl ester and hexanal, one predominant compound in
      oxidized AA, on mouse taste perception of monosodium glutamate (MSG). METHOD: We
      examined the effects of oxidized ethyl AA and hexanal on chorda tympani (CT)
      nerve response to MSG using mouse electrophysiological technique. In addition, we
      evaluated the effects of aliphatic aldehydes and alcohol which are compounds
      structurally related to hexanal with carbon chain lengths or a functional group
      different from hexanal on taste perception of MSG using behavioral and
      electrophysiological studies. RESULT: The CT nerve responses to 10, 20, and 50 mM
      MSG with water extracts of oxidized ethyl AA was higher than that to MSG alone. A
      total of 1000 uM hexanal and pentanal enhanced mouse taste response to MSG, but
      1000 uM propanal and 1-hexanol failed to increase the responses. DISCUSSION: The
      products of oxidized ethyl AA and hexanal would enhance the taste sensation of
      MSG, which suggests that CT nerve input should be important for projection to the
      behavioral responses. The carbon chain length and the functional group of hexanal
      would be key factors of the hexanal effect on mouse taste perception of MSG.

PMID- 23541368
TI  - Smoke alarm: mental illness and tobacco.

PMID- 23541369
TI  - Early nutrition and adult outcomes: pieces of the puzzle.

PMID- 23541371
TI  - Endothelin-3 expression in the subfornical organ enhances the sensitivity of
      Na(x), the brain sodium-level sensor, to suppress salt intake.
AB  - Salt homeostasis is essential to survival, but brain mechanisms for salt-intake
      control have not been fully elucidated. Here, we found that the sensitivity of
      Na(x) channels to [Na(+)](o) is dose-dependently enhanced by endothelin-3 (ET-3).
      Na(x) channels began to open when [Na(+)](o) exceeded ~150 mM without ET-3, but
      opened fully at a physiological [Na(+)](o) (135-145 mM) with 1 nM ET-3.
      Importantly, ET-3 was expressed in the subfornical organ (SFO) along with Nax,
      and the level was robustly increased by dehydration. Pharmacological experiments
      revealed that endothelin receptor B (ET(B)R) signaling is involved in this
      modulation of Na(x) gating through protein kinase C and ERK1/2 activation. ET(B)R
      agonists increased the firing rate of GABAergic neurons via lactate in the SFO,
      and an ET(B)R antagonist attenuated salt aversion during dehydration. These
      results indicate that ET-3 expression in the SFO is tightly coupled with body
      fluid homeostasis through modulation of the [Na(+)](o) sensitivity of Na(x).

PMID- 23541370
TI  - Associations of linear growth and relative weight gain during early life with
      adult health and human capital in countries of low and middle income: findings
      from five birth cohort studies.
AB  - BACKGROUND: Fast weight gain and linear growth in children in low-income and
      middle-income countries are associated with enhanced survival and improved
      cognitive development, but might increase risk of obesity and related adult
      cardiometabolic diseases. We investigated how linear growth and relative weight
      gain during infancy and childhood are related to health and human capital
      outcomes in young adults. METHODS: We used data from five prospective birth
      cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa.
      We investigated body-mass index, systolic and diastolic blood pressure, plasma
      glucose concentration, height, years of attained schooling, and related
      categorical indicators of adverse outcomes in young adults. With linear and
      logistic regression models, we assessed how these outcomes relate to birthweight
      and to statistically independent measures representing linear growth and weight
      gain independent of linear growth (relative weight gain) in three age periods: 0
      2 years, 2 years to mid-childhood, and mid-childhood to adulthood. FINDINGS: We
      obtained data for 8362 participants who had at least one adult outcome of
      interest. A higher birthweight was consistently associated with an adult body
      mass index of greater than 25 kg/m(2) (odds ratio 1.28, 95% CI 1.21-1.35) and a
      reduced likelihood of short adult stature (0.49, 0.44-0.54) and of not completing
      secondary school (0.82, 0.78-0.87). Faster linear growth was strongly associated
      with a reduced risk of short adult stature (age 2 years: 0.23, 0.20-0.52; mid
      childhood: 0.39, 0.36-0.43) and of not completing secondary school (age 2 years:
      0.74, 0.67-0.78; mid-childhood: 0.87, 0.83-0.92), but did raise the likelihood of
      overweight (age 2 years: 1.24, 1.17-1.31; mid-childhood: 1.12, 1.06-1.18) and
      elevated blood pressure (age 2 years: 1.12, 1.06-1.19; mid-childhood: 1.07, 1.01
      1.13). Faster relative weight gain was associated with an increased risk of adult
      overweight (age 2 years: 1.51, 1.43-1.60; mid-childhood: 1.76, 1.69-1.91) and
      elevated blood pressure (age 2 years: 1.07, 1.01-1.13; mid-childhood: 1.22, 1.15
      1.30). Linear growth and relative weight gain were not associated with
      dysglycaemia, but a higher birthweight was associated with decreased risk of the
      disorder (0.89, 0.81-0.98). INTERPRETATION: Interventions in countries of low and
      middle income to increase birthweight and linear growth during the first 2 years
      of life are likely to result in substantial gains in height and schooling and
      give some protection from adult chronic disease risk factors, with few adverse
      trade-offs. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation.

PMID- 23541373
TI  - Not what it looks like: a transient cardiomyopathy.

PMID- 23541372
TI  - Hypothalamic mTORC1 signaling controls sympathetic nerve activity and arterial
      pressure and mediates leptin effects.
AB  - The fundamental importance of the hypothalamus in the regulation of autonomic and
      cardiovascular functions is well established. However, the molecular processes
      involved are not well understood. Here, we show that the mammalian (or
      mechanistic) target of rapamycin (mTOR) signaling in the hypothalamus is tied to
      the activity of the sympathetic nervous system and to cardiovascular function.
      Modulation of mTOR complex 1 (mTORC1) signaling caused dramatic changes in
      sympathetic traffic, blood flow, and arterial pressure. Our data also demonstrate
      the importance of hypothalamic mTORC1 signaling in transducing the sympathetic
      and cardiovascular actions of leptin. Moreover, we show that the PI3K pathway
      links the leptin receptor to mTORC1 signaling and that changes in its activity
      impact sympathetic traffic and arterial pressure. These findings establish mTORC1
      activity in the hypothalamus as a key determinant of sympathetic and
      cardiovascular regulation and suggest that dysregulated hypothalamic mTORC1
      activity may influence the development of cardiovascular diseases.

PMID- 23541374
TI  - Cumulative radiation dose from medical imaging in chronic adult patients.
AB  - Chronic patients require ongoing care that results in repeated imaging and
      exposure to ionizing radiation for both diagnostic and therapeutic purposes. This
      is of concern due to the long-term effects of radiation exposure, namely the
      association between radiation and increased cancer risk. In this study, the
      scientific literature on cumulated dose of radiation accrued from medical imaging
      by 4 cohorts of chronic patients (cardiac disease, end-stage kidney disease,
      inflammatory bowel disease, and patients undergoing endovascular aortic repair)
      was systematically reviewed. We found that the cumulative effective dose is
      moderate in cardiac and inflammatory bowel disease patients, high in end-stage
      kidney disease patients, and very high in endovascular aortic repair patients. We
      concluded that radiation burden of medical imaging is high in selected cohorts of
      chronic patients. Efforts should be implemented to reduce this cumulative dose
      and its potential attendant risks.

PMID- 23541375
TI  - Cheyne-stokes breathing and reduced ejection fraction.
AB  - BACKGROUND: The accuracy of Cheyne-Stokes breathing as a sign of left ventricular
      dysfunction and its overall prognostic significance are unknown. METHODS: Between
      2001 and 2006, the author examined 386 inpatients at a Department of Veterans
      Affairs Medical Center and compared the finding of Cheyne-Stokes breathing and
      its cycle length with the patients' echocardiographic ejection fraction (EF) and
      5-year survival. RESULTS: A total of 45 of 386 patients (11.7%) had Cheyne-Stokes
      breathing. Two variables were independently associated with Cheyne-Stokes
      breathing: reduced EF (P<.001) and age>80 years (P=.006). The presence of Cheyne
      Stokes breathing increased the probability of a markedly reduced EF (ie, EF<40%;
      likelihood ratio, 5.3; 95% confidence interval, 3.1-9), especially in patients
      aged<=80 years (likelihood ratio, 7.8; 95% confidence interval, 3.9-15.5). The
      finding was present in 1 of 3 affected patients (sensitivity=34%). The
      correlation between cycle length and EF was poor (r=0.23, P=.14). The 5-year
      survival of patients with Cheyne-Stokes breathing (37.2%) was similar to that of
      patients without the finding (42.9%, P=.18, log-rank test). CONCLUSIONS: In
      hospitalized patients, Cheyne-Stokes breathing increases the probability of left
      ventricular dysfunction. It is present in 1 of 3 patients with markedly reduced
      EF. When detected during physical examination, Cheyne-Stokes breathing does not
      indicate worse prognosis.

PMID- 23541376
TI  - Systolic blood pressure and cardiovascular outcomes during treatment of
      hypertension.
AB  - OBJECTIVE: Randomized controlled trials in hypertension demonstrate
      cardiovascular benefits when systolic blood pressures are reduced from higher
      values to<160 mm Hg. The value of lower targets has not been fully defined,
      although major guidelines recommend achieving systolic blood pressures of<140 mm
      Hg. This study was conducted to explore cardiovascular outcomes at differing on
      treatment blood pressure levels. METHODS: On the basis of a prespecified plan to
      explore relationships between clinical outcomes and systolic blood pressures, the
      pooled cohort of high-risk hypertensive patients (N=10,705) in the Avoiding
      Cardiovascular Events through Combination Therapy in Patients Living with
      Systolic Hypertension trial were divided into 4 strata of systolic blood pressure
      levels: >140 mm Hg, 130 to <140 mm Hg, 120 to <130 mm Hg, and 110 to <120 mm Hg.
      The primary end point was cardiovascular death or nonfatal myocardial infarction
      or stroke. Outcomes comparisons between the blood pressure groups were by Cox
      regression. RESULTS: The mean patient age was 68 years, and the study duration
      was 35.7 months. The primary end point occurred in 171 of 3429 patients (5.0%)
      with systolic blood pressure in the 10 mm Hg range<140 and in 179 of 2354
      patients (7.6%) with systolic blood pressure>=140 mm Hg (hazard ratio [HR], 0.62;
      95% CI, 0.50-0.77; P=.0001). Likewise, cardiovascular death decreased by 36%
      (P=.0147), total myocardial infarction (fatal+nonfatal) decreased by 37%
      (P=.0028), and stroke decreased by 47% (P=.0002). Cardiovascular event rates in
      those with systolic blood pressure<130 mm Hg were not different from those with
      systolic blood pressure<140 mm Hg. However, compared with systolic blood
      pressure<130 mm Hg, stroke incidence in those with systolic blood pressure<120 mm
      Hg was lower (HR, 0.60; 95% CI, 0.35-1.01; P=.0529), but myocardial function was
      higher (HR, 1.52; 95% CI, 1.00-2.29; P=.0437), as were composite coronary events
      (myocardial infarction, hospitalized angina, or sudden death) (HR, 1.63; 95% CI,
      1.18-2.24; P=.0023). The renal end point of a sustained>50% increase in serum
      creatinine was significantly lower in those with systolic blood pressure<140 mm
      Hg than in any of the other higher or lower blood pressure ranges. CONCLUSIONS:
      In high-risk hypertensive patients, major cardiovascular events are significantly
      lower in those with systolic blood pressures<140 mm Hg and<130 mm Hg than in
      those with levels>140 mm Hg. There are stroke benefits at levels<120 mm Hg, but
      they are offset by increased coronary events. Renal function is best protected in
      the 130 to 139 mm Hg range.

PMID- 23541377
TI  - An unusual presenting complaint for herpes zoster.

PMID- 23541379
TI  - Pharmacokinetic studies of protein drugs: past, present and future.
AB  - Among the growing number of therapeutic proteins on the market, there is an
      emergence of biotherapeutics designed from our comprehension of the physiological
      mechanisms responsible for their peripheral and tissue pharmacokinetics. Most of
      them have been optimized to increase their half-life through glycosylation
      engineering, polyethylene glycol conjugation or Fc fusion. However, our
      understanding of biological drug behaviors is still its infancy compared to the
      huge amount of data regarding small molecular weight drugs accumulated over half
      a century. Unfortunately, therapeutic proteins share few resemblances with these
      drugs. For instance drug-targeted-mediated disposition, binding to
      glycoreceptors, lysosomal recycling, large hydrodynamic volume and electrostatic
      charge are typical critical characteristics that cannot be derived from our
      anterior knowledge of classical drugs. However, the numerous discoveries made in
      the two last decades have driven and will continue to drive new options in
      biochemical engineering and support the design of complex delivery systems. Most
      of these new developments will be supported by novel analytical methods for
      assessing in vitro or in vivo metabolism parameters. 

PMID- 23541378
TI  - Estradiol stimulates an anti-translocation expression pattern of glucocorticoid
      co-regulators in a hippocampal cell model.
AB  - A consistent clinical finding in patients with major depressive disorder (MDD) is
      hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the system in the
      body that facilitates the response to stress. It has been suggested that
      alterations in glucocorticoid receptor (GR)-mediated feedback prolong activation
      of the HPA axis, leading to the dysfunction observed in MDD. Additionally, the
      risk for developing MDD is heightened by several risk factors, namely gender,
      genetics and early life stress. Previous studies have demonstrated that GR
      translocation is sexually dimorphic and this difference may be facilitated by
      differential expression of GR co-regulators. The purpose of this study was to
      determine the extent to which ovarian hormones alter expression of GR and its co
      regulators, Fkbp5 and Ppid, in HT-22 hippocampal neurons. The impact of
      corticosterone (cort), estradiol (E2), and progesterone (P4) treatments on the
      expression of the genes Nr3c1, Ppid, and Fkbp5 was assessed in HT-22 hippocampal
      neurons. Treatment of cells with increasing doses of cort increased the
      expression of Fkbp5, an effect that was potentiated by E2. Exposure of HT-22
      cells to E2 decreased the expression of Ppid and simultaneous exposure to E2 and
      P4 had combinatory effects on Ppid expression. The effects of E2 on Ppid extend
      previous work which demonstrated that serum E2 concentrations correlate with
      hippocampal Ppid expression in female rats. The results presented here illustrate
      that E2 generates an anti-translocation pattern of GR co-regulators in
      hippocampal cells. 

PMID- 23541380
TI  - Genome-scale analysis of the metabolic networks of oleaginous Zygomycete fungi.
AB  - Microbial lipids are becoming an attractive option for the industrial production
      of foods and oleochemicals. To investigate the lipid physiology of the oleaginous
      microorganisms, at the system level, genome-scale metabolic networks of
      Mortierella alpina and Mucor circinelloides were constructed using bioinformatics
      and systems biology. As scaffolds for integrated data analysis focusing on lipid
      production, consensus metabolic routes governing fatty acid synthesis, and lipid
      storage and mobilisation were identified by comparative analysis of developed
      metabolic networks. Unique metabolic features were identified in individual
      fungi, particularly in NADPH metabolism and sterol biosynthesis, which might be
      related to differences in fungal lipid phenotypes. The frameworks detailing the
      metabolic relationship between M. alpina and M. circinelloides generated in this
      study is useful for further elucidation of the microbial oleaginicity, which
      might lead to the production improvement of microbial oils as alternative
      feedstocks for oleochemical industry.

PMID- 23541382
TI  - The Neandertal vertebral column 1: the cervical spine.
AB  - This paper provides a metric analysis of the Neandertal cervical spine in
      relation to modern human variation. All seven cervical vertebrae have been
      analysed. Metric data from eight Neandertal individuals are compared with a large
      sample of modern humans. The significance of morphometric differences is tested
      using both z-scores and two-tailed Wilcoxon signed rank tests. The results
      identify significant metric and morphological differences between Neandertals and
      modern humans in all seven cervical vertebrae. Neandertal vertebrae are
      mediolaterally wider and dorsoventrally longer than modern humans, due in part to
      longer and more horizontally oriented spinous processes. This suggests that
      Neandertal cervical morphology was more stable in both mid-sagittal and coronal
      planes. It is hypothesized that the differences in cranial size and shape in the
      Neandertal and modern human lineages from their Middle Pleistocene ancestors
      could account for some of the differences in the neck anatomy between these
      species.

PMID- 23541381
TI  - Depression inhibits the anti-inflammatory effects of leisure time physical
      activity and light to moderate alcohol consumption.
AB  - Light to moderate alcohol consumption and leisure time physical activity (LTPA)
      are independently associated with lower levels of high sensitivity C-reactive
      protein (CRP), a predictor of cardiometabolic risk. In contrast, depression,
      ranging from low mood disturbance to major depressive disorder, has been
      associated with elevated CRP. To test the hypothesis that depression attenuates
      the anti-inflammatory effects of LTPA and alcohol consumption, the current study
      tested the moderating effect of severity of depressive symptomatology on the
      relation of alcohol consumption and LTPA to CRP in 222 healthy adult men and
      women (18-65 years of age). Given the known effects of gender on inflammation, we
      also examined the effects of gender on the tested interactions. Depression was
      assessed using the Beck Depression Inventory. Frequency of alcohol consumption,
      hours of LTPA per week and other coronary risk/protective factors were assessed
      via self-report and structured interview. Fasting blood samples were used to
      measure CRP and lipids. As predicted, the interaction between LTPA and depressive
      symptomatology was significant (F=5.29, p<.03) such that lower CRP was associated
      with the combination of decreased depressive symptomatology and increased LTPA.
      Among those with increased depressive symptoms, increased LTPA was not associated
      with higher CRP. Similarly, depression interacted with alcohol consumption in
      predicting CRP in men but not women (F=5.03, p<.008) such that for men light to
      moderate alcohol consumption was associated with lower CRP but only among those
      with decreased depressive symptoms. Light to moderate alcohol consumption was not
      associated with lower CRP in those with increased depressive symptom severity.
      The pattern of the interactions between anti-inflammatory activities such as
      light to moderate alcohol consumption and LTPA and psychological distress as
      indexed by severity of depressive symptomatology suggests an important new avenue
      for future research.

PMID- 23541383
TI  - Thickened cranial vault and parasagittal keeling: correlated traits and
      autapomorphies of Homo erectus?
AB  - Homo erectus sensu lato (s.l.) is a key species in the hominin fossil record for
      the study of human evolution, being one of the first species discovered and
      perhaps the most documented, but also because of its long temporal range and
      having dispersed out of Africa earlier than any other human species. Here I test
      two proposed autapomorphic traits of H. erectus, namely the increased thickness
      of the upper cranial vault and parasagittal keeling. The definition of these two
      anatomical features and their expression and variation among hominids are
      discussed. The results of this study indicate that the upper vault in Asian H.
      erectus is not absolutely thicker compared with fossil anatomically modern Homo
      sapiens, whereas Broken Hill and Petralona have values above the range of
      variation of H. erectus. Moreover, this anatomical region in Asian H. erectus is
      not significantly thicker compared with Pan paniscus. In addition, these results
      demonstrate that cranial vault thickness should not be used to make hypotheses
      regarding sexual attribution of fossil hominin specimens. I also show that the
      relation between relief on the external surface of the upper vault, parasagittal
      keeling and bregmatic eminence, and bone thickness is complex. In this context,
      the autapomorphic status of the two analysed traits in H. erectus may be
      rejected. Nevertheless, different patterns in the distribution of bone thickness
      on the upper vault were identified. Some individual variations are visible, but
      specificities are observable in samples of different species. The pattern of bone
      thickness distribution observed in Asian H. erectus, P. paniscus, possibly
      australopiths, and early Homo or Homo ergaster/erectus appears to be shared by
      these different species and would be a plesiomorphic trait among hominids. In
      contrast, two apomorphic states for this feature were identified for Neandertals
      and H. sapiens.

PMID- 23541384
TI  - Microtomographic archive of fossil hominin specimens from Kromdraai B, South
      Africa.
AB  - The Ditsong National Museum of Natural History (DNMNH) and the Max Planck
      Institute for Evolutionary Anthropology (MPI-EVA) established a collaboration in
      2010 to scan fossil hominin specimens housed at DNMNH using microtomography
      (microCT). The goal of this collaboration is to facilitate research and create a
      'virtual copy' of the fossils for the DNMNH records. Within the context of this
      ongoing collaboration, the focus of this contribution is the fossil hominin
      material from the site of Kromdraai B, South Africa. The goals are to 1) formally
      publish the microCT scans of the Kromdraai material and facilitate their
      availability to the scientific research community, 2) address uncertainties
      regarding specimen accession numbers, 3) highlight internal aspects of anatomy
      revealed through the microCT scans, and 4) clarify the hominin status of a number
      of postcranial specimens. Finally, 2D images of surface models, a 3D PDF surface
      model, a movie of each microCT volume, and the original microCT volume of each
      specimen are made available via an open access online archive
      (http://paleo.eva.mpg.de).

PMID- 23541385
TI  - Modeling trophic resource availability for the first human settlers of Europe:
      the case of Atapuerca TD6.
AB  - Food resource availability strongly influences the survival opportunities of all
      organisms. The effect of animal food resource availability on the survival and
      dispersal of hominin populations is hotly debated. In this article, we present a
      mathematical model that provides estimations of the maximum and minimum available
      resources for secondary consumers in a palaeocommunity. This model provides
      insights into the intensity of competition and the available niche space for
      hominins in Europe during the early Galerian (1.2-0.8 Ma). Published data from
      the Atapuerca TD6 assemblage were used in combination with the model to
      investigate trophic dynamics and resource availability for a Homo antecessor
      population 800,000 years ago. The effect on our results of the possible presence
      at Atapuerca of some large carnivores not recorded in the fossil assemblage is
      also evaluated. Results indicate the existence of a rich ecosystem at Atapuerca
      at the end of the Early Pleistocene. Secondary production was abundant enough to
      maintain a hunter-gatherer population and a rich carnivore guild more diverse
      than that recorded in the TD6 assemblage. Based on these results, the practice of
      cannibalism by H. antecessor cannot be explained by a long-term scarcity of
      resources. High food availability at TD6 implies a low to moderate level of
      competition for resources between carnivores and humans. According to this
      interpretation, an empty niche for a highly carnivorous omnivore existed in
      Europe during the early Galerian, and it was successfully exploited by Homo.

PMID- 23541386
TI  - To the Editor-out-of-service lead.

PMID- 23541387
TI  - Reply to the editor-out of service lead.

PMID- 23541388
TI  - Immunohistological characterization of spinal TB granulomas from HIV-negative and
      -positive patients.
AB  - Tuberculosis (TB) is mainly a disease of the lungs, but Mycobacterium
      tuberculosis (Mtb) can establish infection in virtually any organ in the body.
      Rising rates of extrapulmonary (EP) TB have been largely associated with the HIV
      epidemic, as patients co-infected with HIV show a four-fold higher risk of EPTB.
      Spinal TB (Pott's Disease), one of the most debilitating extrapulmonary forms of
      disease, is difficult to diagnose and can cause deformity and/or neurological
      deficits. This study examined the histopathology and distribution of immune cells
      within spinal TB lesions and the impact of HIV on pathogenesis. The overall
      structure of the spinal granulomas resembled that seen in lung lesions from
      patients with pulmonary TB. Evidence of efficient macrophage activation and
      differentiation were detectable within organized structures in the spinal tissue,
      irrespective of HIV status. Interestingly, the granulomatous architecture and
      macroscopic features were similar in all samples examined, despite a reversal in
      the ratio of infiltrating CD4 to CD8 T cells in the lesions from HIV-infected
      patients. This study provides a foundation to understand the mechanism of tissue
      destruction and disease progression in Spinal TB, enabling the future development
      of novel therapeutic strategies and diagnostic approaches for this devastating
      disease.

PMID- 23541389
TI  - Trypanosoma cruzi infection induces morphological reorganization of the
      myocardium parenchyma and stroma, and modifies the mechanical properties of
      atrial and ventricular cardiomyocytes in rats.
AB  - BACKGROUND: This study investigates morphofunctional adaptations of the heart
      stroma and parenchyma in rats that are chronically infected with Trypanosoma
      cruzi. METHODS: Four-month-old male Wistar rats were randomized into control
      (n=14) and infected (n=14) groups. Infected animals were inoculated with T. cruzi
      Y strain. After 9 weeks, the animals were euthanized, and the right atrium (RA)
      and left ventricle (LV) were removed for biochemical, stereological, and
      cardiomyocyte mechanical analyses. RESULTS: Infected animals presented
      cardiomyocyte atrophy and myocardial fibrosis. For these animals, the total
      volume, length, surface area, and cross-sectional area of cardiomyocytes were
      significantly reduced, and the total interstitial and collagen volumes were
      significantly increased in the RA and LV compared to the controls. The total
      volume and length of blood vessels were significantly increased in the LV, and
      the total blood vessel surface area was significantly higher in the RA of
      infected animals. RA and LV cardiomyocytes from infected animals exhibited a
      significant reduction in cell shortening (43.02% and 24.98%, respectively),
      prolongation of the time to the peak of contraction (17.09%) and the time to half
      relaxation (23.68%) compared to non-infected animals. Lipid hydroperoxides, but
      not mineral concentrations, were significantly increased in the RA and LV from
      infected animals, showing an inverse correlation with cell shortening.
      CONCLUSIONS: T. cruzi infection induces global structural remodeling of the RA
      and LV in rats. This remodeling coexists with cardiomyocyte contractility
      dysfunction, which is possibly related to the abnormal organization of the
      myocardial stroma and increased cellular lipid peroxidation.

PMID- 23541390
TI  - Localized high-resolution DTI of the human midbrain using single-shot EPI,
      parallel imaging, and outer-volume suppression at 7T.
AB  - Localized high-resolution diffusion tensor images (DTI) from the midbrain were
      obtained using reduced field-of-view (rFOV) methods combined with SENSE parallel
      imaging and single-shot echo planar (EPI) acquisitions at 7T. This combination
      aimed to diminish sensitivities of DTI to motion, susceptibility variations, and
      EPI artifacts at ultra-high field. Outer-volume suppression (OVS) was applied in
      DTI acquisitions at 2- and 1-mm(2) resolutions, b=1000s/mm(2), and six diffusion
      directions, resulting in scans of 7- and 14-min durations. Mean apparent
      diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured
      in various fiber tract locations at the two resolutions and compared. Geometric
      distortion and signal-to-noise ratio (SNR) were additionally measured and
      compared for reduced-FOV and full-FOV DTI scans. Up to an eight-fold data
      reduction was achieved using DTI-OVS with SENSE at 1mm(2), and geometric
      distortion was halved. The localization of fiber tracts was improved, enabling
      targeted FA and ADC measurements. Significant differences in diffusion properties
      were observed between resolutions for a number of regions suggesting that FA
      values are impacted by partial volume effects even at a 2-mm(2) resolution. The
      combined SENSE DTI-OVS approach allows large reductions in DTI data acquisition
      and provides improved quality for high-resolution diffusion studies of the human
      brain.

PMID- 23541391
TI  - Distribution and abundance of small plastic debris on beaches in the SE Pacific
      (Chile): a study supported by a citizen science project.
AB  - The accumulation of large and small plastic debris is a problem throughout the
      world's oceans and coastlines. Abundances and types of small plastic debris have
      only been reported for some isolated beaches in the SE Pacific, but these data
      are insufficient to evaluate the situation in this region. The citizen science
      project "National Sampling of Small Plastic Debris" was supported by
      schoolchildren from all over Chile who documented the distribution and abundance
      of small plastic debris on Chilean beaches. Thirty-nine schools and nearly 1000
      students from continental Chile and Easter Island participated in the activity.
      To validate the data obtained by the students, all samples were recounted in the
      laboratory. The results of the present study showed that the students were able
      to follow the instructions and generate reliable data. The average abundance
      obtained was 27 small plastic pieces per m(2) for the continental coast of Chile,
      but the samples from Easter Island had extraordinarily higher abundances (>800
      items per m(2)). The abundance of small plastic debris on the continental coast
      could be associated with coastal urban centers and their economic activities. The
      high abundance found on Easter Island can be explained mainly by the transport of
      plastic debris via the surface currents in the South Pacific Subtropical Gyre,
      resulting in the accumulation of small plastic debris on the beaches of the
      island. This first report of the widespread distribution and abundance of small
      plastic debris on Chilean beaches underscores the need to extend plastic debris
      research to ecological aspects of the problem and to improve waste management.

PMID- 23541392
TI  - The HIV risk reduction needs of homeless women in Los Angeles.
AB  - BACKGROUND: Substance use, housing instability, and transactional sex all
      contribute to HIV risk engagement among homeless women. Because of the increased
      risk of HIV among homeless women, this study sought to understand the context of
      sexual behaviors and condom use among homeless women and elucidate modifiable
      factors that can be targeted by interventions. METHODS: Homeless women (n = 45)
      participated in focus groups (n = 6) at shelters throughout Los Angeles County.
      Thematic analyses revealed that similar to other high-risk women, homeless women
      engage in sex with multiple types of partners (steady, casual, and
      transactional). FINDINGS: Our findings indicate that, similar to use among other
      high-risk women, condom use by homeless women varied by type of partner.
      Substance use also contributed to condom non-use. In a departure from previous
      research, homeless women reported overarching feelings of hopelessness.
      Participants spoke of hopelessness contributing to risk engagement, specifically
      the number of ongoing stressors experienced because of homelessness contributing
      to despair. Without acknowledgement of this unique quality of homelessness, women
      felt their risk reduction needs would never truly be understood. CONCLUSIONS:
      Interventions involving homeless women should include self-esteem building,
      acknowledgment and use of inherent resilience qualities gained during
      homelessness, respect for current knowledge and skills, and an exploration of
      when women choose to trust their partners and how they make safer sex choices.

PMID- 23541393
TI  - Long-term botulinum toxin treatment of benign essential blepharospasm, hemifacial
      spasm, and Meige syndrome.
AB  - PURPOSE: To report the clinical success and incidence of adverse events of
      repetitive botulinum toxin treatment of 15 years or greater. DESIGN:
      Retrospective cohort study. METHODS: The study sample consisted of 37 patients
      from a clinical practice, 11 male and 26 female. Inclusion criteria consisted of
      patients treated a minimum of 15 consecutive years for facial dystonia. Seven
      patients had hemifacial spasm, 4 Meige syndrome, and 26 benign essential
      blepharospasm. Main outcome measures consisted of treatment efficacy and adverse
      events. RESULTS: Mean treatment duration was 19.4 years (SD 2.2) with an average
      of 62 (SD 22) treatments of 70.2 (SD 20.8) neurotoxin units. Mean duration of
      treatment efficacy was 127 days (SD 37) with a 5% physician-reported minor
      adverse event rate and no major adverse events over each patient's clinical
      course. Patients reported no major and 20% incidence of minor adverse events over
      the treatment course. CONCLUSION: Results suggest that long-term botulinum toxin
      treatment produces clinical success in the alleviation of facial dystonia
      symptoms. Treatment produced a low incidence of major adverse events and minor
      adverse events. Previous studies may under-report clinical success and over
      report adverse events because of study design.

PMID- 23541394
TI  - Intraocular lens delivery characteristics of the preloaded AcrySof IQ
      SN60WS/AcrySert injectable lens system.
AB  - OBJECTIVE: To evaluate the delivery characteristics of the AcrySof IQ SN60WS
      intraocular lens (IOL) injected via a preloaded AcrySert delivery system. DESIGN:
      Prospective observational case series. METHODS: setting: This study was carried
      out in the cataract service of an ophthalmic hospital that serves a large sector
      of inner-city London. patient population: The study included all patients
      undergoing routine phacoemulsification procedures with implantation of the SN60WS
      IOL via the preloaded system over 5 consecutive months. A total of 85 patients
      (85 eyes) were included in this study. intervention: Phacoemulsification
      procedures conducted by 7 surgeons were digitally captured. outcome measures:
      Video recordings of the IOL delivery stage were analyzed by a single observer. Of
      particular interests were the orientation of the leading haptic and optic on
      insertion, the degree of intrawound manipulation of the injector, and the time
      required to satisfactorily deliver the IOL into the capsular bag in a correct
      orientation. Problems of IOL delivery were also noted. RESULTS: In 38 out of 85
      eyes (45%), correct IOL delivery behavior was achieved with the leading haptic
      orientating to the left of the surgeon and thus did not require any intrawound
      rotational manipulation of the injector. Forty-seven of the 85 eyes (55%)
      required additional rotational manipulation of IOL orientation. Other problems
      recorded were trapped trailing haptic, haptic-optic adhesion, overriding of the
      plunger over the optic, and trauma to optic edge. The average time to achieve
      satisfactory IOL position was 47 seconds. IOL power and the grade of the
      operating surgeon did not appear to influence the event of a misdirected leading
      haptic. CONCLUSIONS: The AcrySof SN60WS/AcrySert system does not appear to meet
      the expectations of pro-viding a predictable means of IOL delivery.

PMID- 23541395
TI  - Inequalities in the distribution of pharmacists' wage-and-salary earnings:
      indicators and their development.
AB  - BACKGROUND: Disparities in wages and salaries can be viewed as the dispersion of
      a statistical distribution that responds to observed and unobserved
      characteristics, and reflects socioeconomic phenomena such as the interplay of
      supply and demand, availability of information, and efficiency of markets in
      their search for equilibrium. OBJECTIVES: The aim of this study was to explore
      the nature of inequality in the distribution of pharmacists' wage-and-salary
      earnings and establish the extent to which inequality primarily occurred because
      of variation between/among groups or within groups of pharmacists in several
      classifications of human-capital and job-related preference variables. METHODS:
      Data were collected through the use of a survey questionnaire mailed to
      registered pharmacists in South Florida, USA. Five indicators of inequality (the
      log earnings variance, the coefficient of variation, the lower median share, the
      90-10 decile ratio, and the Gini coefficient) were estimated for eight human
      capital classifications and eight job-related classifications. A one-way ANOVA
      model was applied to the groups in each classification to compare variation
      between/among versus within pharmacy groups. RESULTS: Pharmacists' wage-and
      salary earnings were more evenly distributed than most income distributions
      discussed in the literature. They were more equitably distributed for full-time
      pharmacists than for all pharmacists in the data set. All five-inequality
      indicators behaved similarly. Notable differences were observed between/among
      groups within the gender, age group, marital status, number of children, academic
      degree, and type of primary pharmacy activity classifications. CONCLUSION:
      Inequalities in wages and salaries have been identified both between/among and
      within pharmacist groups in several classifications using five commonly accepted
      indicators.

PMID- 23541396
TI  - Equilibrium population dynamics when mating is by mutual choice based on age.
AB  - We consider a steady state model of mutual mate choice in which an individual's
      mate preferences depend on his/her age, and the preferences are over the ages of
      prospective mates of the opposite sex. We present a discrete time (and age) model
      corresponding to successive mating seasons. Males are fertile for m periods
      (corresponding to 'age' i=1 to m) and females for n<=m periods (they have ages
      j=1 to n), which is all that distinguishes the sexes. Although we can deal with
      arbitrary preferences, we concentrate on a simple fertility model where the
      common utility to a male age i and female age j who mate is the number K=min(m
      i+1,n-j+1) of future periods of joint fertility. The incoming sex ratio R of age
      1 males to age 1 females is given exogenously. In each period individuals are
      randomly (non assortatively) matched and form a mated couple by mutual consent;
      otherwise they go into the next period unmated and older. We derive properties of
      equilibrium threshold acceptance strategies and establish the existence of time
      invariant age distributions. Our methods determine the age distribution of
      couples at marriage (mating) and the population sex ratio (OSR) at equilibrium.
      Since this can be determined empirically in a population, our model can be used
      to rule out most systems of age preferences (those not consistent with the
      observed distribution). This extends earlier models of mutual choice with one
      dimensional types of Alpern and Reyniers [1999. Strategic mating with homotypic
      preferences. J. Theor. Biol. 198, 71-88; 2005. Strategic mating with common
      preferences. J. Theor. Biol. 237, 337-354] where individuals sought,
      respectively, individuals with similar or high types, but in those models an
      individual's type was fixed over time. Under the simple fertility model, at
      equilibrium the maximum age of an acceptable partner is increasing in the age of
      the searcher. Our results relate to discussions in the literature regarding
      optimal parental age differences, age-related mate preferences, and to mate
      choice in general. We believe our model will be used as a tool in future
      investigations in these areas. 

PMID- 23541397
TI  - Longitudinal MRI study of the midline brain regions in first-episode
      schizophrenia.
AB  - This magnetic resonance imaging (MRI) study investigated the prevalence and size
      of the adhesio interthalamica (AI) and cavum septi pellucidi (CSP) in 64 first
      episode schizophrenia patients and 64 controls, of whom longitudinal data were
      available for 20 patients and 21 controls. The AI was shorter in the patients and
      showed longitudinal decline in both groups; there was also a trend for AI atrophy
      to correlate with negative symptoms. The CSP showed no group difference. These
      results suggest a role for the AI as a possible neurodevelopmental marker of
      schizophrenia.

PMID- 23541398
TI  - Do maternal body dissatisfaction and dietary restraint predict weight gain in
      young pre-school children? A 1-year follow-up study.
AB  - BACKGROUND: The relationships between maternal body image and eating concerns and
      increases in body mass index (BMI) in early childhood are poorly understood. Our
      aim was to test a model in which mothers' BMI, body dissatisfaction, dietary
      restraint and concerns about their child's weight were related to restrictive
      feeding practices and child BMIz change. METHODS: Mothers of 2-year-old children
      (n=202, aged between 1.5 and 2.5years) reported concerns regarding their own and
      their child's weight, their dietary restraint, and restrictive feeding practices.
      Height and weight were measured for children and reported by mothers at baseline
      and 1-year later. RESULTS: Thirty five percent of mothers and 29% of children
      were in overweight or obese categories at baseline. Using path analysis, after
      adding an additional pathway to the proposed model the final model provided a
      good fit to the data (chi(2) (8)=5.593, p=.693, CFI=1.000, RMSEA=.000), with
      maternal dietary restraint directly predicting change in child BMIz over the
      year. Concern about child's weight and, to a lesser extent, maternal dietary
      restraint mediated the relationship between maternal body dissatisfaction and the
      use of restrictive feeding practices. However, the pathway from restrictive
      feeding practices to change in child BMIz was not significant. CONCLUSIONS:
      Mothers' BMI and body dissatisfaction may contribute indirectly to weight change
      in their young children. Interventions targeting maternal body dissatisfaction
      and informing about effective feeding strategies may help prevent increases in
      child BMIz.

PMID- 23541399
TI  - Androgen deprivation from pre-puberty to peripuberty interferes in proteins
      expression in pubertal and adult rat epididymis.
AB  - Few studies have focused on experimental testosterone deprivation in immature
      animals. Therefore, this study used sexually immature rats aiming to evaluate the
      testes and epididymis histology and proteins expression in these organs on PND50
      and 75, after premature antiandrogen exposure, from PND21 to 44. Although the
      androgen deprivation from pre-puberty up to peripuberty did not alter the
      histological organization of the testes and epididymis either at puberty or at
      adulthood, the treatment impaired the expression of specific proteins in
      epididymal tissue at puberty and adulthood (androgen receptor, calmodulin,
      Rab11A). These changes may be related to impaired epididymal function, sperm
      quality and fertility capacity as observed in a previous study. Further studies
      are necessary to better investigate the molecular mechanisms involved in the
      impairment on reproductive competence of male rats after precocious hormonal
      injury.

PMID- 23541400
TI  - Downscaled climate change projections with uncertainty assessment over India
      using a high resolution multi-model approach.
AB  - This study presents the possible regional climate change over South Asia with a
      focus over India as simulated by three very high resolution regional climate
      models (RCMs). One of the most striking results is a robust increase in monsoon
      precipitation by the end of the 21st century but regional differences in
      strength. First the ability of RCMs to simulate the monsoon climate is analyzed.
      For this purpose all three RCMs are forced with ECMWF reanalysis data for the
      period 1989-2008 at a horizontal resolution of ~25 km. The results are compared
      against independent observations. In order to simulate future climate the models
      are driven by lateral boundary conditions from two global climate models (GCMs:
      ECHAM5-MPIOM and HadCM3) using the SRES A1B scenario, except for one RCM, which
      only used data from one GCM. The results are presented for the full transient
      simulation period 1970-2099 and also for several time slices. The analysis
      concentrates on precipitation and temperature over land. All models show a clear
      signal of gradually wide-spread warming throughout the 21st century. The ensemble
      mean warming over India is 1.5 degrees C at the end of 2050, whereas it is 3.9
      degrees C at the end of century with respect to 1970-1999. The pattern of
      projected precipitation changes shows considerable spatial variability, with an
      increase in precipitation over the peninsular of India and coastal areas and,
      either no change or decrease further inland. From the analysis of a larger
      ensemble of global climate models using the A1B scenario a wide spread warming
      (~3.2 degrees C) and an overall increase (~8.5%) in mean monsoon precipitation by
      the end of the 21st century is very likely. The influence of the driving GCM on
      the projected precipitation change simulated with each RCM is as strong as the
      variability among the RCMs driven with one.

PMID- 23541401
TI  - Soil carbon stocks in Sarawak, Malaysia.
AB  - The relationship between greenhouse gas emission and climate change has led to
      research to identify and manage the natural sources and sinks of the gases. CO2,
      CH4, and N2O have an anthropic source and of these CO2 is the least effective in
      trapping long wave radiation. Soil carbon sequestration can best be described as
      a process of removing carbon dioxide from the atmosphere and relocating into
      soils in a form that is not readily released back into the atmosphere. The
      purpose of this study is to estimate carbon stocks available under current
      conditions in Sarawak, Malaysia. SOC estimates are made for a standard depth of
      100 cm unless the soil by definition is less than this depth, as in the case of
      lithic subgroups. Among the mineral soils, Inceptisols tend to generally have the
      highest carbon contents (about 25 kg m(-2) m(-1)), while Oxisols and Ultisols
      rate second (about 10-15 kg m(-2) m(-1)). The Oxisols store a good amount of
      carbon because of an appreciable time-frame to sequester carbon and possibly
      lower decomposition rates for the organic carbon that is found at 1m depths. Wet
      soils such as peatlands tend to store significant amounts of carbon. The highest
      values estimated for such soils are about 114 kg m(-2) m(-1). Such appreciable
      amounts can also be found in the Aquepts. In conclusion, it is pertinent to
      recognize that degradation of the carbon pool, just like desertification, is a
      real process and that this irreversible process must be addressed immediately.
      Therefore, appropriate soil management practices should be instituted to
      sequester large masses of soil carbon on an annual basis. This knowledge can be
      used effectively to formulate strategies to prevent forest fires and clearing:
      two processes that can quickly release sequestered carbon to the atmosphere in an
      almost irreversible manner.

PMID- 23541402
TI  - Effect of maternal chronic disease on obstetric complications in twin pregnancies
      in a United States cohort.
AB  - OBJECTIVE: To evaluate the effect of maternal chronic disease on obstetric
      complications among twin pregnancies. DESIGN: Multicenter, retrospective,
      observational study. SETTING: Clinical centers (19 hospitals). PATIENT(S): Twin
      pregnancies (n = 4,821) delivered >= 23 weeks of gestation and classified by
      maternal chronic disease (either none or any of the following: asthma,
      depression, hypertension, diabetes, and heart, thyroid, gastrointestinal or renal
      disease). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gestational age at
      delivery, gestational hypertension, pre-eclampsia, gestational diabetes,
      placental abruption, placenta previa, hemorrhage, chorioamnionitis, maternal
      postpartum fever, premature rupture of membranes, labor onset (spontaneous vs.
      nonspontaneous), route of delivery, and maternal admission to intensive care
      unit. RESULT(S): Women with chronic disease delivered earlier (mean gestational
      length, 34.1 vs. 34.6 weeks) and were less likely to have term birth (risk ratio
      0.80; 95% confidence interval 0.70-0.90). Cesarean delivery after spontaneous
      labor (risk ratio 1.20; 95% confidence interval 1.05-1.37) was also increased
      with chronic disease. No statistically significant effects were observed for
      other complications studied. Women who used assisted reproductive technology were
      more likely to hemorrhage, independent of chronic disease, but other findings
      were generally similar to the non-assisted reproductive technology sample.
      CONCLUSION(S): Chronic disease was associated with additional risk of earlier
      delivery and cesarean section after spontaneous labor in a nationwide sample of
      US twin pregnancies.

PMID- 23541403
TI  - Prolactin and proinflammatory cytokine expression at the fetomaternal interface
      in first trimester miscarriage.
AB  - OBJECTIVE: To investigate the expression of prolactin (PRL), PRL-receptor (PRL
      R), and the TH1 cytokines interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF
      alpha), and interferon-gamma (IFN-gamma) at the maternofetal interface. DESIGN:
      Case-control study. SETTING: University hospital unit of gynecology and
      obstetrics and research laboratories. PATIENT(S): Women undergoing suction
      curettage for spontaneous miscarriage (study group) and voluntary termination of
      pregnancy (control group) in the first trimester. INTERVENTION(S): Samples of
      decidua and villi collected and histologically examined at the time of suction
      curettage. MAIN OUTCOME MEASURE(S): Evaluation of all villous samples for
      karyotype with only euploid cases included; detection of transcripts of PRL, PRL
      R, TNF-alpha, IFN-gamma, and IL-2 by qualitative reverse-transcriptase-polymerase
      chain reaction (RT-PCR); investigation of pattern and site of expression by
      immunohistochemistry. RESULT(S): In both groups, PRL-R and IFN-gamma were broadly
      expressed. The expression of PRL was impaired or absent in the villi of the study
      group compared with controls. Expression of TNF-alpha was reduced, although not
      statistically significantly, in both decidual and villous samples of the study
      group. Immunohistochemical analysis showed the lack of IL-2 expression in
      decidual specimens of the control group versus the full expression shown in the
      study group. CONCLUSION(S): Our results highlight the correspondence between PRL
      expression and vital pregnancy and the involvement of the TH1 cytokines with
      different specific roles at the implantation site. Prolactin and IL-2 may
      reciprocally influence expression.

PMID- 23541404
TI  - Consideration of the gestational carrier: a committee opinion.
AB  - Gestational carriers have a right to be fully informed of the risks of the
      surrogacy process and of pregnancy, should receive psychological evaluation and
      counseling, and should have independent legal counsel.

PMID- 23541405
TI  - Is vitrification of oocytes useful for fertility preservation for age-related
      fertility decline and in cancer patients?
AB  - The aim of this review is to provide current knowledge on oocyte
      cryopreservation, with special emphasis on vitrification as a means to preserve
      fertility in different indications. Major advancements achieved in the past few
      years in the cryolaboratory have facilitated major changes in our practice. Areas
      such as fertility preservation for social or oncologic reasons, the possibility
      to create oocyte banks for egg donation programs, the opportunity to avoid
      ovarian hyperstimulation syndrome, or to accumulate oocytes in low-yield
      patients, or even to offer treatment segmentation by stimulating the ovaries,
      vitrifying, and then transferring in a natural cycle are some of the options that
      are now available with the development of cryopreservation. We present general
      experience from our group and others on fertility preservation for age-related
      fertility decline as well as in oncologic patients, confirming that oocyte
      vitrification is a standardized, simple, reproducible, and efficient option.

PMID- 23541406
TI  - Risk of transferring malignant cells with transplanted frozen-thawed ovarian
      tissue.
AB  - Ovarian tissue cryopreservation and transplantation is a real option to preserve
      and restore fertility in young cancer patients. However, there is a concern
      regarding the possible presence of malignant cells in the ovarian tissue, which
      could lead to recurrence of the primary disease after reimplantation. A review of
      the existing literature was done to evaluate the risk of transplanting malignant
      cells in case of the main malignant indications for ovarian tissue
      cryopreservation. For ovarian tissue from patients with hematologic malignancies,
      it is of paramount importance to identify minimal residual disease before ovarian
      tissue transplantation. Indeed, these pathologies, reviewed here in detail, are
      considered to be most at risk of ovarian metastasis.

PMID- 23541407
TI  - Vasectomy demographics and postvasectomy desire for future children: results from
      a contemporary national survey.
AB  - OBJECTIVE: To describe the longitudinal demographics and family planning
      attitudes of vasectomized men with the use of the National Survey for Family
      Growth (NSFG). DESIGN: Retrospective cohort analysis of the NSFG with the use of
      national projections and multivariable regressions. SETTING: In-home survey.
      PATIENT(S): The NSFG sampled 10,403 men aged 15-45 years from 2006 to 2010
      regarding family planning attitudes. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Vasectomy and desire for children. RESULT(S): There were 3,646,339
      (6.6%) vasectomized men aged 18-45 years in the U.S. On multivariable regression
      the following factors increased the odds of having a vasectomy: currently married
      (odds ratio [OR] 7.814), previously married (OR 5.865), and increased age (OR
      1.122) and income (OR 1.003). The odds of having a vasectomy increased with
      number of children. The following factors decreased the odds of having a
      vasectomy: immigrant status (OR 0.186), African American (OR 0.226), Hispanic (OR
      0.543), Catholic (OR 0.549), and other non-Protestant religion (OR 0.109).
      Surprisingly, an estimated 714,682 (19.6%) vasectomized men in the U.S. desire
      future children. Men practicing a religion (OR 8.575-15.843) were more likely
      than atheists to desire children after vasectomy. 71,886 (2.0%) vasectomized men
      reported having a vasectomy reversal. CONCLUSION(S): This study highlights the
      importance of preoperative counseling for permanency of vasectomy and reveals an
      opportunity to counsel couples about vasectomy versus tubal ligation.

PMID- 23541408
TI  - Early beta-human chorionic gonadotropin trends in vanishing twin pregnancies.
AB  - OBJECTIVE: To describe the early beta-hCG trends in vanishing twins compared with
      normally progressing singleton and twin pregnancies. DESIGN: Retrospective cohort
      study. SETTING: University-based infertility clinic. PATIENT(S): Women undergoing
      fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 1998 and 2010.
      INTERVENTION(S): Early beta-hCG level increase in vanished twin pregnancies was
      compared with the level increase in normally progressing singleton and twin
      pregnancies. MAIN OUTCOME MEASURE(S): Two-day percent increase in beta-hCG level.
      RESULT(S): Pregnancies with vanishing twins demonstrated a significantly lower
      mean 2-day percent increase in beta-hCG level than singletons and twins (114.3%
      vs. 128.8% and 125.4%, respectively). Vanishing twins arresting at earlier
      developmental stages demonstrated significantly further reduced beta-hCG level
      increases. Infrequently, all groups had beta-hCG level increases less than
      previously established clinical thresholds that led to a live birth.
      CONCLUSION(S): Early beta-hCG level increases are slower in vanishing twins than
      in singleton and twin pregnancies, with the slowest increases seen when the
      spontaneous fetal losses occur at earlier developmental stages. All increases,
      however, are within clinically accepted normal limits. Therefore, abnormal beta
      hCG level increases should not be attributed to a vanishing twin. Of note, an
      abnormal beta-hCG level trend--even an initial decrease--does not preclude live
      birth, even in a singleton pregnancy.

PMID- 23541409
TI  - Phylogenetic character mapping of RADES Probing, a new marker for exploring the
      clonal evolution of expressed coding sequences in Trypanosoma cruzi, the agent of
      Chagas disease.
AB  - We have tested a new genetic marker, RADES Probing (RADES-P), on a standard
      sample of 19 laboratory-cloned stocks of Trypanosoma cruzi, the agent of Chagas
      disease. This set of stocks, fully characterized using multilocus enzyme
      electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD), is
      representative of this parasite's main genetic subdivisions. RADES-P consists in
      hybridizing RAPD profiles with probes composed of the products of random
      amplified differentially expressed sequences (RADES). The profiles thus obtained
      uncover only expressed coding sequences that are as well present on RAPD gels.
      Direct visual examination and the banding record show that these RADES-P profiles
      are different of, and not redundant with, both RAPD and RADES patterns obtained
      on the same set of stocks with the same primers. Phylogenetic character mapping
      (PCM) of the RADES-P polymorphism fairly confirms the known population structure
      and phylogenetic diversity of T. cruzi. This suggests that the impact of clonal
      evolution on T. cruzi has been predominant enough over the long term to carve the
      polymorphism of all types of DNA sequences, including polymorphisms of expressed
      coding sequences, although these sequences are subject to natural selection. 

PMID- 23541410
TI  - Phylogenetic analysis of lack gene sequences for 22 Chinese Leishmania isolates.
AB  - OBJECTIVES: The phylogenetic relationships between Chinese Leishmania strains
      were investigated using lack (Leishmania homolog of receptors for activated
      protein kinase C) gene sequences, and the power of this gene was assessed for
      understanding the epidemiology and population genetics of Leishmania. METHODS:
      The lack gene sequences from Leishmania isolates were sequenced after polymerase
      chain reaction (PCR) amplification. Sequence alignment was performed and a
      phylogenetic tree was created using the MEGA 5.0 software program. RESULTS:
      Sequences of 850 bp were analyzed for each of the Leishmania strains collected
      from different locations in China, and minor differences in sequences were noted
      between the strains. Four distinct groups formed according to differences in the
      sequences of the lack gene. Group I consisted of 12 isolates from Shandong,
      Xinjiang, Gansu and Sichuan. These strains are part of the Leishmania donovani
      complex and are pathogenic to humans and canines. Group II included six isolates
      from Xinjiang and a reference strain, Leishmania turanica. Group III contained
      two isolates (one from a sand fly in Xinjiang and one from a rodent in Inner
      Mongolia) and they were identified as Leishmania gerbilli. Finally, group IV
      contained a strain from a sand fly in Xinjiang and a strain from a lizard in
      Inner Mongolia, and these strains were found to be Sauroleishmania. CONCLUSION:
      The Chinese Leishmania isolates formed four groups based on differences in the
      sequences of the lack gene, and this result is consistent with previous studies.
      Phylogenetic analysis suggests that the Leishmania isolates from China are more
      complicated than previously thought. There is consensus between genetic
      clustering and identification using classical methods, which means that the lack
      gene yields polymorphic information that could be used for genotyping Leishmania
      isolates.

PMID- 23541411
TI  - Staphylococcus aureus toxins--their functions and genetics.
AB  - The outcome of encounters between Staphylococcus (S.) aureus and its human host
      ranges from life-threatening infection through allergic reactions to symptom-free
      colonization. The pan-genome of this bacterial species encodes numerous toxins,
      known or strongly suspected to cause specific diseases or symptoms. Three toxin
      families are in the focus of this review, namely (i) pore-forming toxins, (ii)
      exfoliative toxins and (iii) superantigens. The majority of toxin-encoding genes
      are located on mobile genetic elements (MGEs), resulting in a pronounced
      heterogeneity in the endowment with toxin genes of individual S. aureus strains.
      Recent population genomic analysis have provided a framework for an improved
      understanding of the temporal and spatial scales of the motility of MGEs and
      their associated toxin genes. The distribution of toxin genes among clonal
      lineages within the species S. aureus is not random, and phylogenetic (sub
      )lineages within clonal complexes feature characteristic toxin signatures. When
      studying pathogenesis, this lineage association, which is caused by the clonal
      nature of S. aureus makes it difficult to discriminate effects of specific toxins
      from contributions of the genetic background and/or other associated genetic
      factors. 

PMID- 23541412
TI  - HLA-G 3' UTR-2 haplotype is associated with Human African trypanosomiasis
      susceptibility.
AB  - Trypanosoma brucei gambiense (Tbg) is responsible for the chronic form of Human
      African trypanosomiasis (HAT), classically lasting for years. Clinical evolution
      of HAT cases seems to be complex and reports on asymptomatic carriers and
      spontaneous cure have been published recently, strengthening the likely existence
      of the phenomenon of human trypanotolerance. Host's genetic factors could be
      involved in both the control of infection levels and the mortality rates, as
      clearly shown in experimental models, but also in human. Although genes directly
      involved in immune response are important candidates, genes implicated in the
      regulation of immunity, such as HLA-G, could also play a critical role. A
      candidate gene association study was previously conducted in the Democratic
      Republic of Congo using a family-based sample including 106 families (n=353). All
      individuals, from the Yansi ethnic group, were born in the area and had been
      exposed to the risk of infection since birth. We sequenced the HLA-G 3'
      untranslated region (UTR) and performed a family based association analysis of
      the 14 polymorphisms identified (14-bp insertion/deletion plus 13 SNPs). Three
      polymorphisms, 14-bp insertion/deletion and SNPs located at the +3003 and +3196
      positions were associated to HAT (FBAT p=0.008, p=0.015 and p=0.022,
      respectively). HLA-G 3'UTR haplotypes were significantly associated with HAT
      (HBAT, global p=0.0026). UTR-2 haplotype (including 14-pb insertion and G allele
      at position +3196) was over-transmitted to the affected offspring (HBAT p=0.003)
      at the expense of UTR-4 haplotype, which was under-transmitted (HBAT p=0.013).
      These results are the first to report an association between polymorphisms in HLA
      G and variable risks to develop HAT and suggest the involvement of the HLA-G
      molecule on HAT susceptibility.

PMID- 23541414
TI  - Nucleic acid testing for blood banks: an experience from a tertiary care centre
      in New Delhi, India.
AB  - INTRODUCTION: Blood safety is a challenging task in India; with a population of
      around 1.23 billion and a high prevalence rate of HIV (0.29%), HBV (2-8%) and HCV
      (~ 2%) in general population. Nucleic acid testing (NAT) in blood donor screening
      has been implemented in many developed countries to reduce the risk of
      transfusion-transmitted viral infections (TTIs). NAT shortens this window period,
      thereby offering blood centers a much higher sensitivity for detecting viral
      infections. MATERIALS AND METHODS: Routine ID-NAT for HIV-1, HCV and HBV was
      started from June 2010 at AIIMS blood bank by the Procleix(r) Ultrio(r) Assay
      (Novartis Diagnostics, USA) a multiplex NAT, which allows the simultaneous
      detection of HIV-1, HCV, and HBV in a single tube. During the period of 27 months
      from June 2010 to August 2012, around 73,898 samples were tested for all the
      three viruses using both ELISA (by Genscreen Ultra HIV Ag-Ab(BIO-RAD),
      Hepanostika HCV Ultra & HBsAg Ultra(Biomerieux) and Nucleic acid testing. The
      comparative results of both the assays are being presented here in this study.
      RESULTS: Out of 73,898 samples, 1104 samples (1.49%) were reactive by NAT. out of
      these 1104 samples, 73 were reactive for HIV-1 (0.09%), 186 were reactive for HCV
      only (0.25%), 779 (1.05%) were reactive for HBV only, and around 66 (0.08%) were
      HBV-HCV co-infections. There was one HIV, 37 HCV, 73 HBV and 10 HBV-HCV co
      infection cases that were not detected by serology but reactive on NAT testing,
      with a combined yield of 1 in 610 donations (total 121 NAT yields). CONCLUSION:
      NAT could detect HIV, HBV and HCV cases in blood donor samples that were
      undetected by serological tests. NAT can interdict a large number of infected
      unit transfusions and thus help in providing safe blood to the patients.

PMID- 23541415
TI  - Effect of leonurine hydrochloride on endothelin and the endothelin receptor
      mediated signal pathway in medically-induced incomplete abortion in rats.
AB  - OBJECTIVE: Endothelin (ET) is involved in uterine contractions. Our previous
      study showed that leonurine hydrochloride (LH) inhibits abnormal bleeding caused
      by incomplete abortion through an increase in uterine contractions in rats. The
      present study was conducted to show that LH treatment regulates the ET-mediated
      signal pathway in abortion in rats. STUDY DESIGN: Early pregnancies in rats had
      incomplete abortions induced using mifepristone in combination with misoprostol.
      After the abortions, the rats were treated with LH orally for 7 days and surgery
      was performed. The sinistro-uterus was dissected for measurement of ET and nitric
      oxide (NO); the dextro-uterus was stored at -80 degrees C for ET receptor (ETA
      and ETB) analysis. Myometrial cells from the dextro-uterus were cultured for
      measurement of phospholipase C (PLC) activity, intra-cellular Ca(2+)
      concentration ([Ca(2+)]i), and protein kinase C (PKC) activity. RESULTS: In in
      vivo experiments, LH treatment elevated the ET level and ET/NO ratio in rats with
      induced abortions and up-regulated ETA mRNA expression (P<0.01 vs. the model
      group), but there was no change in ETB mRNA. LH significantly increased the
      [Ca(2+)]i, PLC activity, and relative production of PKC protein in myometrial
      cells. CONCLUSION: LH increased uterine contractions in rats with incomplete
      abortions by modulating the ET receptor-mediated signal pathway.

PMID- 23541416
TI  - HOXA10 protein expression in the endometrium of normally menstruating women after
      receiving GnRH antagonist.
AB  - OBJECTIVE(S): To compare HOXA10 protein expression in the endometrium between
      natural control cycles and GnRH antagonist-treated cycles obtained during the
      window of implantation of normally menstruating women. STUDY DESIGN: This study
      was conducted at the Department of Obstetrics and Gynecology, Faculty of
      Medicine, Chulalongkorn University, Bangkok, Thailand. Thirty-five volunteers
      were recruited into this prospective, self-controlled study, which was divided
      into two cycles, the first a natural control cycle and the second a GnRH
      antagonist-treated cycle. The two cycles were separated by one resting cycle. In
      the GnRH antagonist-treated cycle, when the leading follicle was 15 mm, ganirelix
      (Orgalutran(r)) 0.25mg was administered daily. In both cycles, ovulation was
      induced when the largest follicle reached 18 mm in diameter. Finally, endometrial
      biopsy was performed on day 6 after documented ovulation, which corresponds to
      the window of implantation. Endometrial HOXA10 protein expression, a marker of
      endometrial receptivity, was analyzed by immunohistochemistry. The protein
      expression was compared between the two cycles regarding their percentage of
      immunostained cells and IHC-scores (percentage of stained cells*intensity of
      nuclear staining). RESULTS: HOXA10 protein was exclusively localized in the
      stromal compartment of the endometrium. The percentage of HOXA10 nuclear staining
      in the endometrium collected from GnRH antagonist-treated cycles was higher than
      that of the natural cycles, whereas the IHC-scores showed no difference between
      the two cycles. CONCLUSION(S): GnRH antagonists may have no effect on HOXA10
      protein expression in the endometrium obtained during the implantation window of
      normally menstruating women.

PMID- 23541417
TI  - Advantages of recombinant follicle-stimulating hormone over human menopausal
      gonadotropin for ovarian stimulation in intrauterine insemination: a randomized
      clinical trial in unexplained infertility.
AB  - OBJECTIVE: To compare two different gonadotropin preparations, human menopausal
      gonadotropin (hMG) and recombinant follicle-stimulating hormone (rFSH), combined
      with clomiphene citrate (CC) in women with unexplained infertility undergoing
      intrauterine insemination (IUI). STUDY DESIGN: In this prospective clinical
      trial, couples prepared for IUI cycles were randomly allocated to two groups
      either to receive CC and hMG (group A, n=127) or CC and rFSH (group B, n=132) for
      ovarian stimulation. Outcomes including rates of clinical pregnancy, miscarriage,
      OHSS, multiple pregnancy, cancellation, and live birth were compared between
      groups. RESULTS: Duration of gonadotropin therapy was significantly shorter in
      group B (5.1+/-0.84 vs. 4.7+/-0.8 days, CI=95%, P<0.001). The total dose of
      administered gonadotropin was also significantly lower in group B (386.9+/-68.2
      vs. 348.2+/-56.3IU, CI=95%, P<0.001). Dominant follicle number (>17mm), mean
      follicular diameter, and endometrial thickness on the day of hCG injection were
      similar. Clinical pregnancy, multiple pregnancies, abortion, live birth, ovarian
      hyperstimulation syndrome (OHSS), and cancellation rates were not statistically
      different between the groups. CONCLUSION: IUI cycles in which rFSH had been
      administered may require shorter duration and a lower total gonadotropin dose.

PMID- 23541413
TI  - Connecting the study of wild influenza with the potential for pandemic disease.
AB  - Continuing outbreaks of pathogenic (H5N1) and pandemic (SOIVH1N1) influenza have
      underscored the need to understand the origin, characteristics, and evolution of
      novel influenza A virus (IAV) variants that pose a threat to human health. In the
      last 4-5years, focus has been placed on the organization of large-scale
      surveillance programs to examine the phylogenetics of avian influenza virus (AIV)
      and host-virus relationships in domestic and wild animals. Here we review the
      current gaps in wild animal and environmental surveillance and the current
      understanding of genetic signatures in potentially pandemic strains.

PMID- 23541418
TI  - Dietary triacyglycerols rich in sn-2 palmitate alter post-prandial lipoprotein
      and unesterified fatty acids in term infants.
AB  - Human milk TAG contain 20-25% 16:0, with over 70% of the 16:0 at the TAG sn-2
      position. The benefits of TAG sn-2 16:0 have been ascribed to reducing 16:0
      excretion as insoluble fatty acid soaps. This study builds on knowledge that
      infants conserve milk TG sn-2 16:0 post-absorption. Comparison of plasma lipids
      from 120 day old infants fed formula containing 25-27% 16:0 with 29% 16:0 or 5%
      16:0 at the TAG sn-2 position showed higher formula sn-2 16:0 led to lower 18:1n
      9, but higher 18:2n-6 and 22:6n-3 in the infant plasma unesterified fatty acids,
      higher 18:0 in LDL TAG, and higher apo B and lower apo A-1. TAG-sn-2 16:0 may
      provide 16:0 in remnant particles for hepatic elongation to 18:0, needed for
      plasma and tissue phospholipids. We suggest attention to the plasma unesterified
      fatty acids as possible sources of fatty acids for membrane phospholipid
      synthesis. 

PMID- 23541419
TI  - Increased nasopharyngeal carriage of serotypes 6A, 6C, and 6D Streptococcus
      pneumoniae after introduction of childhood pneumococcal vaccination in Hong Kong.
AB  - Active surveillance on nasopharygeal carriage of Streptococcus pneumoniae in
      children was conducted in 5581 children under 16 years old admitted with
      respiratory illness to the pediatric wards in a Hong Kong teaching hospital
      during 2008-2010. The isolation rate of S. pneumoniae was 14.5%. The most common
      serotypes/groups from 911 isolates were 19F, 6B, 23F, 14, 6C, 6A, and 3.
      Considering only children under 2 years old, the percentage serotype belonging to
      that of the 7-, 10- and 13-valent conjugate pneumococcal vaccines in S.
      pneumoniae were 56.0% (115/205), 57% (117/205), and 80.5% (165/205),
      respectively. The prevalence of penicillin-nonsusceptibility (MIC >=4.0 MUg/mL)
      was 9.1% and for cefotaxime (MIC >=2.0 MUg/mL) was 14.7%. A high prevalence of
      non-6B serotype, including 6A, 6C, and 6D was noted after the introduction of
      PCV7 conjugate pneumococcal vaccines in Hong Kong.

PMID- 23541420
TI  - pH-responsive complexes using prefunctionalized polymers for synchronous delivery
      of doxorubicin and siRNA to cancer cells.
AB  - A nanocarrier delivery system that can simultaneously deliver a chemotherapeutic
      drug and siRNA to the tumor is emerging as a promising treatment strategy for
      cancer treatment. In this study, a multifunctional PHD/PPF/siRNA complexes was
      developed by one-step assembly of prefunctionalized polymers: PEI-HZ-DOX (PHD)
      and PEI-PEG-Folate (PPF) with siRNA. The PHD, a conjugate of PEI
      (polyethylenimine) with doxorubicin (DOX) via a pH-responsive hydrazone linkage,
      enables pH-controlled drug release. The PPF, a tumor-targeting folate ligand
      conjugated to PEI using polyethyleneglycol (PEG) as a linker, enables immune
      evasion and cell-specific targeting. The prefunctionalized PHD and PPF as well as
      the self-assembly complexes reveals advantage on safety in further application
      for siRNA delivery. By exploiting distinct triple ratios of PHD, PPF and siRNA
      during nanocomplexes formulation, the folate surface density, DOX loading amount
      and siRNA complexation can be precisely and reproducibly changed. The studies
      showed that the complexes was capable of delivering siRNA and DOX to cancerous
      cells and release synchronously in cell by acid-triggered manner, i.e. hydrazone
      bond cleavage and endosome/lysosome escape using flow cytometry and confocal
      laser scanning microscopy analysis. The results highlight the potential for
      therapeutic gene silencing in vitro and in vivo using RT-PCR and non-invasive in
      vivo imaging systems. The PHD/PPF/siRNA complexes can increase DOX and siRNA
      accumulation in cancerous cells and decrease the nonspecific distribution in
      normal tissues by the combination of EPR effect of nanocarriers, pH-triggered
      drug release, folate-mediated targeted delivery, and synergistic action of DOX
      and siRNA.

PMID- 23541421
TI  - Short-term bleeding events observed with clopidogrel loading in acute ischemic
      stroke patients.
AB  - INTRODUCTION: The Fast Assessment of Stroke and Transient Ischemic Attack to
      Prevent Early Recurrence trial raised concern that loading doses of clopidogrel
      may increase hemorrhagic complications. We investigated if similar rates of
      hemorrhage occur in patients with acute ischemic stroke (AIS) of varying
      severity. METHODS: Patients meeting inclusion criteria were divided into 2
      groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients
      who were administered a loading dose of 300 mg or more of clopidogrel with or
      without aspirin within 24 hours of admission. The non-LOAD group was devised
      using propensity score (PS): 55 patients who received a loading dose of
      clopidogrel of 300 mg or more were matched on PS to 55 patients who did not
      receive loading doses. These patients were taken from a pool of 341 consecutive
      ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162
      of whom received a clopidogrel loading dose and the remainder of whom did not.
      The frequency of hemorrhage was compared between the 2 groups using Student t
      test and chi-square. Logistic regression was used to assess the relationship
      between loading dose and serious bleeding events (symptomatic intracerebral
      hemorrhage [sICH] or transfusion for systemic bleeding). RESULTS: AIS patients (N
      = 596) were screened during the 31-month period of this retrospective study. Of
      this sample, 170 patients were excluded: 149 patients were excluded because they
      were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11
      were excluded because they were treated with IV t-PA combined with intra-arterial
      therapy (IAT), and 10 were excluded for treatment with IAT alone. An additional
      85 patients were excluded because they were not admitted to the stroke service or
      because they had an in-hospital stroke. Baseline characteristics of the groups
      were well matched. There were no significant differences in the rates of sICH,
      transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel
      loading was not associated with increased odds of serious bleeding events in the
      crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after
      adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04).
      DISCUSSION: Contrary to our original hypothesis, patients with AIS receiving
      clopidogrel loading doses within 24 hours of symptom onset did not appear to
      experience a higher rate of new serious bleeding events during acute
      hospitalization when compared with patients who did not receive loading doses.
      The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is
      expected to provide insight into the safety of clopidogrel loading as an acute
      intervention after cerebral ischemia.

PMID- 23541422
TI  - High-resolution magnetic resonance imaging reveals hidden etiologies of
      symptomatic vertebral arterial lesions.
AB  - BACKGROUND: Symptomatic intracranial vertebral artery (VA) disease has various
      clinical features and poor neurological outcomes. The disease is believed to
      result from atherosclerotic stenosis, occlusion, or spontaneous VA dissection.
      The underlying histopathology of symptomatic intracranial VA disease has only
      been studied at postmortem, and no in vivo imaging investigation has been
      conducted despite the increased sophistication of imaging techniques. METHODS:
      The authors performed high-resolution magnetic resonance imaging (HR-MRI) of
      intracranial vertebral arteries in 9 patients, suspected of a VA pathology by
      magnetic resonance imaging (MRI), magnetic resonance angiography, and digital
      subtraction angiography. RESULTS: HR-MRI allowed the authors to determine the
      following: (1) atherosclerotic plaque is composed of a large lipid core with
      intraplaque hemorrhage and calcification, (2) nonstenotic atherosclerosis
      exhibits diffuse vessel wall thickening and plaque protruding toward perforating
      arteries, and (3) spontaneous VA dissection exhibits large intramural hematoma in
      a false lumen with complete occlusion of the true lumen. In addition, VA
      hypoplasia was easily differentiated from atherosclerotic stenosis, by direct
      visualization of a narrow lumen diameter without arterial wall thickening.
      Furthermore, etiologic diagnoses based on classical MRI, angiography, and digital
      subtraction angiography were changed in 3 patients after HR-MRI. Additional
      information on plaque stability, indicating the possibility of unstable plaque,
      was found in 4 patients. CONCLUSIONS: The application of HR-MRI in stroke
      patients with VA pathologies enabled the authors to determine the underlying
      pathophysiologies. These findings could be used to improve risk stratification
      and treatment decision making in symptomatic intracranial VA disease.

PMID- 23541423
TI  - Cilostazol for the prevention of acute progressing stroke: a multicenter,
      randomized controlled trial.
AB  - BACKGROUND: Progressing stroke is one of the major determinants of outcome after
      acute ischemic stroke. A pilot randomized controlled trial was conducted to
      investigate the effect of cilostazol on progressing stroke. METHODS: Adult
      patients with noncardioembolic ischemic stroke within 24 hours after onset were
      randomized to receive cilostazol 200 mg/day (cilostazol group) or no medication
      (control group) in addition to the optimum medical treatments (a free radical
      scavenger plus an antiplatelet agent or an antithrombin agent). The primary
      endpoints were the rate of progressing stroke, defined as aggravation of the
      National Institutes of Health Stroke Scale (NIHSS) score by >= 4 points on days 3
      and/or 5 and a modified Rankin Scale score of 0 to 1 at 3 months after
      enrollment. Aggravation caused by systemic complications, edema, hemorrhagic
      infarction, or recurrent stroke was not considered as progressing stroke. This
      trial was registered as UMIN000001630. RESULTS: A total of 510 patients were
      enrolled from 55 institutions in Japan between February 2009 and July 2010. The
      rate of progressing stroke was 3.2% and 6.3% in the cilostazol and control
      groups, respectively (P = .143). The modified Rankin Scale score of 0 to 1 at 3
      months did not differ between the groups. CONCLUSIONS: Cilostazol failed to show
      a preventive effect against acute progressing stroke. However, the tendency to
      reduce progressing stroke and the results of stratified analyses may encourage
      additional studies to clarify the effect of cilostazol in the treatment of acute
      ischemic stroke.

PMID- 23541424
TI  - Availability of the northern hemisphere influenza vaccine for Australians
      travelling overseas.

PMID- 23541425
TI  - TRPV1 antagonistic analgesic effect: a randomized study of AZD1386 in pain after
      third molar extraction.
AB  - The effects of a TRPV1 antagonist (AZD1386) were investigated in patients with
      acute pain. After removal of a mandibular third molar and at request of analgesia
      103 patients randomly received 95 mg AZD1386 (n = 40), placebo (n = 40) or 500 mg
      naproxen (n = 23) in a double-blind manner. Plasma samples were drawn, and pain
      intensity and body temperature were measured during 8 h after drug
      administration. The pain intensity difference from drug intake was calculated as
      a percentage (PID%) and as a weighted sum over the 8 h (SPID%0-8 h). The time to
      first perceptible and first meaningful pain relief was recorded. SPID%(0-8) h
      showed no significant difference between AZD1386 and placebo (P = .132) but
      between naproxen and placebo (P = .038). AZD1386 had a rapid short-lasting
      analgesia and compared to placebo, PID% was significantly higher (P <= .026) at
      0.25, 0.50, 0.75 and 1.00 h after drug administration. Correspondingly, for
      naproxen significantly higher PID% (P <= .021) was seen at 2.5, 3, 4, 5, 6, 7 and
      8 h. The frequency of patients obtaining perceptible and meaningful pain relief
      was about 85% and 48% after AZD1386 and about 53% and 25% after placebo. The
      occurrence of perceptible and meaningful pain relief was significantly faster (P
      = .002 and P = .031) for AZD1386 compared to placebo. Adverse events were similar
      to placebo with the exception of 2 patients reporting chills. The highest
      individual body temperature after AZD1386 was 38.1 degrees C, recorded in 2
      patients. In summary, AZD1386 was well tolerated with a rapid analgesia that was
      short lasting despite sustained plasma concentration.

PMID- 23541426
TI  - On the mutual effects of pain and emotion: facial pain expressions enhance pain
      perception and vice versa are perceived as more arousing when feeling pain.
AB  - Perception of emotional stimuli alters the perception of pain. Although facial
      expressions are powerful emotional cues - the expression of pain especially plays
      a crucial role for the experience and communication of pain - research on their
      influence on pain perception is scarce. In addition, the opposite effect of pain
      on the processing of emotion has been elucidated even less. To further scrutinize
      mutual influences of emotion and pain, 22 participants were administered painful
      and nonpainful thermal stimuli while watching dynamic facial expressions
      depicting joy, fear, pain, and a neutral expression. As a control condition of
      low visual complexity, a central fixation cross was presented. Participants rated
      the intensity of the thermal stimuli and evaluated valence and arousal of the
      facial expressions. In addition, facial electromyography was recorded as an index
      of emotion and pain perception. Results show that faces per se, compared to the
      low-level control condition, decreased pain, suggesting a general attention
      modulation of pain by complex (social) stimuli. The facial response to painful
      stimulation revealed a significant correlation with pain intensity ratings. Most
      important, painful thermal stimuli increased the arousal of simultaneously
      presented pain expressions, and in turn, pain expressions resulted in higher pain
      ratings compared to all other facial expressions. These findings demonstrate that
      the modulation of pain and emotion is bidirectional with pain faces being mostly
      prone to having mutual influences, and support the view of interconnections
      between pain and emotion. Furthermore, the special relevance of pain faces for
      the processing of pain was demonstrated.

PMID- 23541427
TI  - Placental mesenchymal stem cells: a unique source for cellular cardiomyoplasty.
AB  - In coronary heart disease, the use of stem cells for regeneration purposes has
      been broadly studied. Whereas bone marrow mesenchymal stem cells remain the most
      extensively investigated, other cell sources have been reported. Here we discuss
      and compare the characteristics of placenta-derived mesenchymal stem cells as a
      novel alternative cell source for cellular cardiomyoplasty. These cells are
      isolated from the human term placenta, which is normally discarded post partum.
      With their lack of ethical conflicts and young age, the readily available
      placenta-derived mesenchymal stem cells could be more suitable for myocardial
      regenerative therapy.

PMID- 23541428
TI  - Outcome of concomitantCox-maze III procedure using an argon-based cryosurgical
      system: a single-center experience with 250 patients.
AB  - BACKGROUND: The Cox-Maze procedure (CM) for atrial fibrillation (AF) is
      associated with a high rate of sinus restoration. This study assessed the safety
      and efficacy of concomitant CM using an argon-based cryosurgical platform only.
      METHODS: Data were collected prospectively for 250 consecutive patients
      undergoing concomitant cryosurgical CM. We examined baseline characteristics,
      perioperative and postoperative outcomes, health-related quality of life (Medical
      Outcomes Trust SF-12 Health Survey and AF Symptom Checklist) and Kaplan-Meier
      survival analysis. RESULTS: Mean age was 64.3 +/- 12.1 years, AF duration was
      35.7 +/- 54.2 months, left atrial size was 5.2 cm (range, 3.1 to 11.0 cm; 16.8% >
      6 cm), 86% had nonparoxysmal AF, with history of cardioversion in 32% and
      catheter ablation in 8%. Concomitant procedures were mitral valve operation in
      69.6%, coronary artery bypass graft in 29.2%, aortic valve replacement in 22.0%,
      with 46% multiple concomitant procedures and 16% with a previous cardiac
      operation. Perioperative outcomes were 5 deaths (2%), 3 strokes (1%), 1 transient
      ischemic attack (<1%), and 4 pacemakers for sinus node dysfunction (2%). There
      were no late thromboembolic events (mean follow-up, 28.2 +/- 23.7 months), and
      11% were taking warfarin for atrial arrhythmia at 1 year. Significant improvement
      in health-related quality of life (p < 0.001) was noted. At 24 months, 92.4% of
      patients were in sinus rhythm; with 82.8% in sinus rhythm off antiarrhythmic
      drugs. Two-year cumulative survival was 91%. CONCLUSIONS: The cryosurgical CM
      procedure can be performed safely and effectively as defined by the low number of
      postoperative morbidities, high return to sinus rhythm off antiarrhythmic drugs,
      and low rate of thromboembolic events, with most patients off anticoagulation by
      2 years.

PMID- 23541430
TI  - Delayed management of blunt traumatic aortic injury: open surgical versus
      endovascular repair.
AB  - BACKGROUND: A growing body of evidence has shown that delayed management of
      traumatic injury of the thoracic aorta determines survival benefits as compared
      with immediate treatment. However, few data exist comparing outcomes after
      delayed open surgical or endovascular management. Accordingly, we reviewed our
      experience with delayed management, stratifying the data according to type of
      repair; open surgical versus endovascular. METHODS: Since 1992, delayed aortic
      repair has represented our first-line management for all blunt traumatic thoracic
      aortic injury (BTTAI) patients, except for those who presented with or became
      unstable due to impending aortic rupture. These patients were converted to urgent
      primary aortic repair. Thus, between 1992 and 2010, a total of 77 BTTAI patients
      were managed according to this policy. There were 57 (74%) men having a mean age
      of 33.4 years. Thirty-one (41.3%) patients underwent open surgical repair (SR),
      44 (58.6%) underwent endovascular repair (ER), and 2 died while awaiting aortic
      repair. At admission, the clinical and trauma characteristics were similar in
      both groups. The trauma-to-repair time span (in days) was 200 (Q1-Q3: 27 to 340)
      and 10 (Q1-Q3: 2 to 79) for SR and ER patients, respectively (p = 0.001). Due to
      unpaired hemodynamic or imaging signs of impending aortic rupture, 15 patients
      required urgent repair, which was endovascular in 11 (25%) cases and surgical in
      4 (12.9%). RESULTS: Overall, hospital mortality was 3.9% (n = 3), being 0% in SR
      patients and 2.3% (n = 1) in ER patients (p = 0.398). No new postoperative
      paraplegia occurred; a cerebellar stroke occurred in 1 (2.3%) ER patient
      receiving intentional coverage of the left subclavian artery. During follow-up
      (96.1% complete at 95 +/- 70 months), no late deaths occurred. At 15 years, the
      estimates of survival and freedom from secondary aortic procedures were 96% and
      100%, respectively. CONCLUSIONS: Delayed management of traumatic aortic injury
      was associated with satisfactory short- and long-term results without significant
      differences between open surgical and endovascular repair. However, the reduced
      invasiveness of endovascular repair can optimize operative timing allowing prompt
      aortic repair in unstable patients, earlier repair in stable patients, and, when
      indicated, easier concomitant non-aortic surgery.

PMID- 23541429
TI  - Adenosine A3 receptor activation attenuates lung ischemia-reperfusion injury.
AB  - BACKGROUND: Severe ischemia-reperfusion (IR) injury leads to primary graft
      dysfunction after lung transplantation. Adenosine receptors modulate inflammation
      after IR, and the adenosine A3 receptor (A3R) is expressed in lung tissue and
      inflammatory cells. This study tests the hypothesis that A3R agonism attenuates
      lung IR injury by a neutrophil-dependent mechanism. METHODS: Wild-type and A3R
      knockout (A3R-/-) mice underwent 1-hour left lung ischemia followed by 2-hours
      reperfusion (IR). A selective A3R agonist, Cl-IB-MECA, was administered (100
      MUg/kg intravenously) 5 minutes prior to ischemia. Study groups included sham,
      IR, and IR+Cl-IB-MECA (n = 6/group). Lung injury was assessed by measuring lung
      function, pulmonary edema, histopathology, and proinflammatory cytokines, and
      myeloperoxidase levels in bronchoalveolar lavage fluid. Parallel in vitro
      experiments were performed to evaluate neutrophil chemotaxis, and neutrophil
      activation was measured after exposure to acute hypoxia and reoxygenation.
      RESULTS: Treatment of wild-type mice with Cl-IB-MECA significantly improved lung
      function and decreased edema, cytokine expression, and neutrophil infiltration
      after IR. The Cl-IB-MECA had no effects in A3R-/- mice; Cl-IB-MECA significantly
      decreased activation of wild-type, but not A3R-/-, neutrophils after acute
      hypoxia and reoxygenation and inhibited chemotaxis of wild-type neutrophils.
      CONCLUSIONS: Exogenous activation of A3R by Cl-IB-MECA attenuates lung
      dysfunction, inflammation, and neutrophil infiltration after IR in wild-type but
      not A3R-/- mice. Results with isolated neutrophils suggest that the protective
      effects of Cl-IB-MECA are due, in part, to the prevention of neutrophil
      activation and chemotaxis. The use of A3R agonists may be a novel therapeutic
      strategy to prevent lung IR injury and primary graft dysfunction after
      transplantation.

PMID- 23541431
TI  - Early and long-term mortality in 536 patients after theCox-maze III procedure: a
      national registry-based study.
AB  - BACKGROUND: The cut-and-sew Cox-maze III procedure is the gold standard for
      surgical treatment of atrial fibrillation. The aim was to study early and long
      term mortality based on registry analyses in Swedish Cox-maze III patients.
      METHODS: Preoperative and early postoperative data were analyzed in 536 patients
      (male/female (425/111), mean age 57 +/- 8.6 years), operated from 1994 to 2009 in
      4 centers; 422 (79%) underwent stand-alone Cox-maze III. Atrial fibrillation was
      paroxysmal in 38% and non-paroxysmal in 62%, mean duration was 7.8 +/- 6.3 years.
      Patients were followed for survival or death in a validated national Cause-of
      Death registry. Risk factors associated with observed survival were identified in
      univariable and multivariable analyses in a standard Cox proportional hazards
      model. RESULTS: Four early deaths (0.7%) occurred due to technical complications.
      At follow-up, 41 of 536 (7.6%) patients had died. Cause of death was
      cardiovascular in 19 of 536 (3.5%). No ischemic stroke-related death was
      registered. Univariable risk factors for all-cause mortality included
      hypertension (hazard ratio [HR] 2.8, confidence interval [CI] 1.5 to 5.3), heart
      failure (HR 2.4, CI 1.3 to 4.3), concomitant surgery (HR 2.2, CI 1.1 to 4.1), and
      postoperative complications (HR 2.5, CI 1.3 to 4.8). Gender, non-paroxysmal
      atrial fibrillation and long arrhythmia duration did not confer increased risk of
      death. Multivariable risk factors were hypertension (HR 2.9, CI 1.5 to 5.5) and
      postoperative complications (HR 2.4, CI 1.2 to 4.6). Survival for cardiovascular
      death at 5, 10, and 15 years was 98%, 96%, and 93%, respectively. CONCLUSIONS:
      Registry-based follow-up showed low early and long-term cardiovascular mortality
      and no stroke-related mortality. This is important baseline information when
      evaluating current surgical and nonsurgical treatment of atrial fibrillation.

PMID- 23541432
TI  - Preservation of motor function after spinal cord ischemia and reperfusion injury
      through microglial inhibition.
AB  - BACKGROUND: Paraplegia remains a devastating complication of thoracoabdominal
      aortic procedures resulting from spinal cord ischemia and reperfusion injury
      (SCIR). Pharmacologic interventions have not proven efficacious in attenuating
      this injury, with poor understanding of the underlying mechanisms. The resident
      macrophages, or microglia in the spinal cord, may play a significant role in
      SCIR. The macrolide antibiotic, minocycline, has been shown in stroke models to
      inhibit microglial activation. This study hypothesized that microglial inhibition
      by minocycline after SCIR will attenuate injury with preservation of motor
      function. METHODS: Mature male C57Bl/6 mice underwent 4 minutes of thoracic
      aortic occlusion with reperfusion. Mice receiving minocycline 30 minutes before
      ischemia and daily thereafter (90 mg/kg and 45 mg/kg, respectively) were compared
      with mice receiving vehicle controls. Hind-limb motor function was measured at 12
      hour intervals, with spinal cord harvest for histologic and immunologic
      comparison at 60 hours. RESULTS: Minocycline treatment significantly preserved
      hind limb motor function in all mice (n = 7) compared with complete paralysis in
      all untreated mice (n = 8), reaching significance from 24 hours of reperfusion
      through 60 hours. Immunofluorescent staining for Iba-1 revealed significant
      inhibition of microglial activation by minocycline treatment. Vehicle control
      sections demonstrated a greater degree of apoptosis compared with minocycline
      treated spinal cord sections. CONCLUSIONS: Minocycline limits microglial
      activation, paralleling functional preservation after aortic cross-clamping.
      These data suggest functional microglia contribute to reperfusion injury after
      spinal cord ischemia. The effects of minocycline demonstrate a potential
      pharmacological therapy as well as demonstrating a potential cellular target in
      preventing paraplegia after aortic intervention.

PMID- 23541434
TI  - Pharmacological study of a new Asp49 phospholipase A(2) (Bbil-TX) isolated from
      Bothriopsis bilineata smargadina (forest viper) venom in vertebrate neuromuscular
      preparations.
AB  - The neuromuscular activity of Bbil-TX, a PLA2 with catalytic activity isolated
      from Bothriopsis bilineata smargadina venom, was examined in chick biventer
      cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. In BC
      preparations, Bbil-TX (0.5-10 MUg/ml) caused time- and concentration-dependent
      blockade that was not reversed by washing; the times for 50% blockade were 87 +/-
      7, 41 +/- 7 and 19 +/- 2 min (mean +/- SEM; n = 4-6) for 1, 5 and 10 MUg/ml,
      respectively. Muscle contractures to exogenous ACh and KCl were unaffected. The
      toxin (10 MUg/ml) also did not affect the twitch-tension of directly-stimulated,
      curarized (10 MUg/ml) BC preparations. However, Bbil-TX (10 MUg/ml) produced mild
      morphological alterations (edematous and/or hyperchromic fibers) in BC; there was
      also a progressive release of CK (from 116 +/- 17 IU/ml (basal) to 710 +/- 91
      IU/ml after 45 min). Bbil-TX (5 MUg/ml)-induced blockade was markedly inhibited
      at 22-24  degrees C and pretreatment with p-bromophenacyl bromide (p-BPB)
      abolished the neuromuscular blockade. Bbil-TX (3-30 MUg/ml, n = 4-6) caused
      partial time- and concentration-dependent blockade in PND preparations (52 +/- 2%
      at the highest concentration). Bbil-TX (30 MUg/ml) also markedly reduced the
      MEPPs frequency [from 26 +/- 2.5 (basal) to 10 +/- 1 after 60 min; n = 5; p <
      0.05] and the quantal content [from 94 +/- 14 (basal) to 24 +/- 3 after 60 min; n
      = 5; p < 0.05] of PND preparations, but caused only minor depolarization of the
      membrane resting potential [from -80 +/- 1 mV (basal) to -66 +/- 2 mV after 120
      min; n = 5; p < 0.05], with no significant change in the depolarizing response to
      exogenous carbachol. These results show that Bbil-TX is a presynaptic PLA2 that
      contributes to the neuromuscular blockade caused by B. b. smargadina venom.

PMID- 23541433
TI  - The effects of chronic alcoholism on cell proliferation in the human brain.
AB  - Neurogenesis continues in the human subventricular zone and to a lesser extent in
      the hippocampal subgranular zone throughout life. Subventricular zone-derived
      neuroblasts migrate to the olfactory bulb where survivors become integrated as
      interneurons and are postulated to contribute to odor discrimination. Adult
      neurogenesis is dysregulated in many neurological, neurovascular and
      neurodegenerative diseases. Alcohol abuse can result in a neurodegenerative
      condition called alcohol-related brain damage. Alcohol-related brain damage
      manifests clinically as cognitive dysfunction and the loss of smell sensation
      (hyposmia) and pathologically as generalized white matter atrophy and focal
      neuronal loss. The exact mechanism linking chronic alcohol intoxication with
      alcohol-related brain damage remains largely unknown but rodent models suggest
      that decreased neurogenesis is an important component. We investigated this idea
      by comparing proliferative events in the subventricular zone and olfactory bulb
      of a well-characterized cohort of 15 chronic alcoholics and 16 age-matched
      controls. In contrast to the findings in animal models there was no difference in
      the number of proliferative cell nuclear antigen-positive cells in the
      subventricular zone of alcoholics (mean+/-SD=28.7+/-20.0) and controls (27.6+/
      18.9, p=1.0). There were also no differences in either the total (p=0.89) or
      proliferative cells (p=0.98) in the granular cell layer of the olfactory bulb.
      Our findings show that chronic alcohol consumption does not affect cell
      proliferation in the human SVZ or olfactory bulb. In fact only microglial
      proliferation could be demonstrated in the latter. Therefore neurogenic deficits
      are unlikely to contribute to hyposmia in chronic alcoholics. 

PMID- 23541435
TI  - Arterial pressure oscillation and muscle sympathetic nerve activity after 20 days
      of head-down bed rest.
AB  - Both spectral power within the low-frequency component, i.e., 0.04 to 0.15 Hz, of
      systolic pressure and muscle sympathetic nerve activity are increased during head
      up tilt. The nerve activity during tilt is altered after space flight and
      exposure to simulated microgravity. In the present study, correlations of the low
      frequency component and the nerve activity were analyzed before and after 20 days
      of -6 degrees  of head-down bed rest. Measurements were performed at -6 degrees 
      head-down bed rest, 0 degrees  (flat), and 30 degrees  and 60 degrees  head-up
      tilt (HUT). Mean arterial pressure during HUT was not different between pre- and
      post-bed rest, but muscle sympathetic nerve activity in post-bed rest
      significantly increased at tilt angles of -6 degrees , 0 degrees , 30 degrees ,
      and 60 degrees  compared with those during pre-bed rest. The low-frequency
      component of systolic pressure also significantly increased during post-bed rest
      compared with pre-bed rest at tilts of 0 degrees , 30 degrees , and 60 degrees .
      The nerve activity and the frequency component were linearly correlated for
      individual (r(2) = 0.51-0.88) and averaged (r(2) = 0.60) values when the values
      included both pre- and post-bed rest. Thus, the low-frequency component of
      systolic pressure could be an index of the muscle sympathetic nerve activity
      during tilt during pre- and post-bed rest.

PMID- 23541436
TI  - Anti-inflammatory effect of essential oil and its constituents from fingered
      citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF
      kappaB signaling pathways in LPS-activated RAW 264.7 cells.
AB  - We investigated the composition of essential oil from fingered citron (Citrus
      medica L. var. sarcodactylis) (FCEO) peels by GC-MS and its anti-inflammatory
      effects on lipopolysaccharide (LPS) - stimulated mouse macrophage (RAW 264.7)
      cells. Fifteen compounds, representing 98.97% of the essential oil, were
      tentatively identified; the main constituents were limonene (52.44%) and gamma
      terpinene (28.41%). FCEO significantly inhibited nitric oxide (NO) and
      prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric
      oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally,
      FCEO suppressed the production of tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, and IL-6. FCEO attenuated LPS-induced nuclear factor
      kappaB (NF-kappaB) activation via inhibition of inhibitor kappaB-alpha
      phosphorylation. Furthermore, FCEO blocked activation of c-Jun N-terminal kinase
      (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen
      activated protein kinase. These results indicate that FCEO inhibits LPS
      stimulated inflammation by blocking the NF-kappaB, JNK, and ERK pathways in
      macrophages, and demonstrate that FCEO possesses anti-inflammatory properties.

PMID- 23541437
TI  - Selenium and mercury molar ratios in commercial fish from New Jersey and
      Illinois: variation within species and relevance to risk communication.
AB  - There is an emerging consensus that people consuming large amounts of fish with
      selenium:mercury ratios below 1 are at higher risk from mercury toxicity. As the
      relative amount of selenium increases compared to mercury, risk may be lowered,
      but it is unclear how much excess selenium is required. It would be useful if the
      selenium:mercury ratio was relatively consistent within a species, but this has
      not been the case in our studies of wild-caught fish. Since most people in
      developed countries and urban areas obtain their fish and other seafood
      commercially, we examined selenium:mercury molar ratios in commercial fish
      purchased in stores and fish markets in central New Jersey and Chicago. There was
      substantial interspecific and intraspecific variation in molar ratios. Across
      species the selenium:mercury molar ratio decreased with increasing mean mercury
      levels, but selenium variation also contributed to the ratio. Few samples had
      selenium:mercury molar ratios below 1, but there was a wide range in ratios,
      complicating the interpretation for use in risk management and communication.
      Before ratios can be used in risk management, more information is needed on
      mercury:selenium interactions and mutual bioavailability, and on the relationship
      between molar ratios and health outcomes. Further, people who are selenium
      deficient may be more at risk from mercury toxicity than others.

PMID- 23541438
TI  - Geraniin down regulates gamma radiation-induced apoptosis by suppressing DNA
      damage.
AB  - Gamma ray irradiation triggers DNA damage and apoptosis of proliferating stem
      cells and peripheral immune cells, resulting in the destruction of intestinal
      crypts and lymphoid system. Geraniin is a natural compound extracts from an
      aquatic plant Nymphaea tetragona and possesses good antioxidant property. In this
      study, we demonstrate that geraniin rescues radiosensitive splenocytes and
      jejunal crypt cells from radiation-induced DNA damage and apoptosis. Isolated
      splenocytes from C57BL/6 mice treated with geraniin were protected against
      radiation injury of 2 Gy irradiation through the enhancement of the proliferation
      and attenuation of DNA damage. Also, geraniin inhibited apoptosis in
      radiosensitive splenocytes by reducing the expression level and immunoreactivity
      of proapoptotic p53 and Bax and increasing those of anti-apoptotic Bcl-2. In mice
      exposed to radiation, geraniin treatment protected splenocytes and intestinal
      crypt cells from radiation-induced cell death. Our results suggest that geraniin
      presents radioprotective effects by regulating DNA damage on splenocytes,
      exerting immunostimulatory capacities and inhibiting apoptosis of radiosensitive
      immune cells and jejunal crypt cells. Therefore, geraniin can be a
      radioprotective agent against gamma-irradiation exposure.

PMID- 23541439
TI  - Increased intra-abdominal fat predicts perioperative complications following
      minimally invasive partial nephrectomy.
AB  - OBJECTIVE: To evaluate the anthropometric measurements of body mass index, outer
      abdominal fat (OAF) and intra-abdominal fat (IAF) for their utility in predicting
      perioperative complications following minimally invasive partial nephrectomy.
      METHODS: We retrospectively reviewed the clinical data of patients who underwent
      a laparoscopic or robotic partial nephrectomy between August 2006 and July 2012
      by a single surgeon. Measurements of OAF and IAF were obtained from preoperative
      cross-sectional imaging available through our institution's imaging archive.
      Preoperative clinical parameters, including BMI, OAF and IAF, were evaluated for
      associations with postoperative complications, operative time and length of
      hospital stay. RESULTS: In total, 257 patients underwent a minimally invasive
      partial nephrectomy during the study period. Of these patients, 195 (75.9%) had
      preoperative scans available for analysis of OAF and IAF. A total of 52 (26.7%)
      patients experienced a Clavien grade I-IV complication within 30 days of surgery,
      18 (34.6%) of which were grade III-IV. No patient experienced a grade V
      complication. On multivariate analysis, only increasing IAF (OR 1.05 [95% CI 1.02
      1.09], P = .005) was associated with grade I-IV complications, while IAF (OR 1.05
      [95% CI 1.00-1.10], P = .04) and intermediate to high tumor complexity (OR 5.31
      [95% CI 1.47-19.17], P = .01) were associated with grade III-IV complications.
      BMI, OAF and IAF were not found to be independently associated with operative
      time or length of hospital stay. CONCLUSION: IAF is independently associated with
      complications following minimally invasive partial nephrectomy. With further
      validation, this measurement may prove useful in the preoperative risk
      stratification of patients with small renal masses.

PMID- 23541440
TI  - Editorial comment.

PMID- 23541441
TI  - Telomere dysfunction and tumor suppression responses in dyskeratosis congenita:
      balancing cancer and tissue renewal impairment.
AB  - Dyskeratosis congenita (DC) encompasses a large spectrum of diseases and clinical
      manifestations generally related to premature aging, including bone marrow
      failure and cancer predisposition. The major risk factor for DC is to carry
      germline telomere-related mutations - in telomerase or telomere shelterin genes -
      which results in premature telomere dysfunction, thus increasing the risk of
      premature aging impairments. Despite the advances that have been accomplished in
      DC research, the molecular aspects underlying the phenotypic variability of the
      disease remain poorly understood. Here different aspects of telomere biology,
      concerning adult stem cells senescence, tumor suppression and cancer are
      considered in the context of DC, resulting in two translational models: late
      onset of DC symptoms in telomere-related mutations carriers is a potential
      indicator of increased cancer risk and differences in tumor suppression
      capacities among the genetic subgroups are (at least partial) causes of different
      clinical manifestations of the disease. The limitations of both models are
      presented, and further experiments for their validation, as well as clinical
      implications, are discussed.

PMID- 23541443
TI  - Enteropathy-associated T-cell lymphoma diagnosed and followed-up by using double
      balloon enteroscopy.

PMID- 23541444
TI  - Diabetes risk assessment models: we have the base, but not enough?

PMID- 23541442
TI  - Interleukin-18 enhances IL-18R/Nox1 binding, and mediates TRAF3IP2-dependent
      smooth muscle cell migration. Inhibition by simvastatin.
AB  - We investigated the role of TRAF3 interacting protein 2 (TRAF3IP2), a redox
      sensitive adapter protein and an upstream regulator of IKK and JNK in interleukin
      (IL)-18 induced smooth muscle cell migration, and the mechanism of its inhibition
      by simvastatin. The pleiotropic cytokine IL-18 induced human coronary artery SMC
      migration through the induction of TRAF3IP2. IL-18 induced Nox1-dependent ROS
      generation, TRAF3IP2 expression, and IKK/NF-kappaB and JNK/AP-1 activation. IL-18
      induced its own expression and that of its receptor subunit IL-18Ralpha. Using co
      IP/IB and GST pull-down assays, we show for the first time that the subunits of
      the IL-18R heterodimer physically associate with Nox1 under basal conditions, and
      IL-18 appears to enhance their binding. Importantly, the HMG-coA reductase
      inhibitor simvastatin attenuated IL-18-induced TRAF3IP2 induction. These
      inhibitory effects were reversed by mevalonate and geranylgeranylpyrophosphate
      (GGPP), but not by farnesylpyrophosphate (FPP). Interestingly, simvastatin, GGPP,
      FPP, or Rac1 inhibition did not modulate ectopically expressed TRAF3IP2. These
      results demonstrate that the promigratory effects of IL-18 are mediated through
      TRAF3IP2 in a redox-sensitive manner, and this may involve IL-18R/Nox1 physical
      association. Further, Simvastatin inhibits inducible, but not ectopically
      xpressed TRAF3IP2. Targeting TRAF3IP2 may blunt progression of hyperplastic
      vascular diseases in vivo.

PMID- 23541445
TI  - Melorheostosis causing lumbar radiculopathy: a case report and a review of the
      literature.
AB  - BACKGROUND CONTEXT: Melorheostosis is a rare sclerosing bone disorder with a
      predilection for the appendicular skeleton. Involvement of the spine is
      infrequent and largely asymptomatic. Surgical treatment for spinal involvement is
      therefore uncommon with only one reported case of lumbar fusion for painful
      lumbosacral melorheostosis. PURPOSE: We report a case of lumbar melorheostosis
      causing disabling radiculopathy treated with nerve root decompression.
      CONCLUSIONS: Melorheostosis of the lumbar spine causing radicular symptoms has
      not been reported before. Our message from the management of this particular
      patient is to consider surgical option in symptomatic individuals.

PMID- 23541446
TI  - Percutaneous injection of augment injectable bone graft (rhPDGF-BB and beta
      tricalcium phosphate [beta-TCP]/bovine type I collagen matrix) increases
      vertebral bone mineral density in geriatric female baboons.
AB  - BACKGROUND CONTEXT: Recombinant human platelet-derived growth factor-BB (rhPDGF
      BB) homodimer is a chemotactic, mitogenic, and angiogenic factor expressed by
      platelets. This biological triad is profoundly important in the bone regenerative
      cascade. Therefore, the expectation was that rhPDGF-BB locally administered to
      designated lumbar vertebrae in a soluble Type I bovine collagen/beta-tricalcium
      phosphate (beta-TCP) injectable paste would have an osteoanabolic effect.
      PURPOSE: The study objective focused on safety and efficacy of the rhPDGF-BB and
      soluble Type I bovine collagen/beta-TCP to increase bone density when injected
      directly into specific lumbar vertebral bodies in elderly (17- to 18-year-old)
      female baboons. STUDY DESIGN/SETTING: The study was designed to determine whether
      vertebral bone mineral density (BMD) in aged female baboons could be increased by
      locally administering recombinant rhPDGF-BB combined in a soluble Type I bovine
      collagen/beta-TCP paste formulation. METHODS: A total of six baboons were divided
      equally into two groups. Group 1 received 1.0 mg/mL rhPDGF-BB in 20 mM sodium
      acetate plus soluble Type I bovine collagen/beta-TCP. Group 2 was treated with 20
      mM sodium acetate plus soluble Type I bovine collagen/beta-TCP. Baboons in each
      group also received a sham surgery. Surgery was conducted using a percutaneous,
      fluoroscopically guided approach, and quantitative computed tomography (qCT) and
      radiographs were done at dedicated time periods. The qCT was used to determine
      volumetric BMD (vBMD). At euthanasia (36-week posttreatment), lumbar vertebrae
      were recovered and analyzed by qCT scans and histology. Funds were received to
      support this work from BioMimetic Therapeutics, Inc. The device that is the
      subject of this manuscript is not Food Drug Administration approved for this
      indication and is not commercially available in the United States. RESULTS: The
      qCT and histopathological data suggested that vBMD and bone morphology increased
      significantly in the lumbar vertebrae treated with the rhPDGF-BB-containing
      composition. CONCLUSIONS: Bone mineral density and bone morphology quality of
      lumbar vertebrae in aged female baboons were improved by direct injection of
      rhPDGF-BB in a soluble Type I bovine collagen/beta-TCP paste. Throughout the
      course of the study, there were neither local nor systemic adverse effects.

PMID- 23541447
TI  - Progressive post-traumatic myelopathy presenting with magnetic resonance imaging
      snake-eye appearance.

PMID- 23541448
TI  - Segmental spinal canal volume in patients with degenerative spondylolisthesis.
AB  - BACKGROUND CONTEXT: Lumbar degenerative spondylolisthesis (DS), typically
      characterized by the forward slippage of the superior vertebra of a lumbar motion
      segment, is a common spinal pathological condition in elderly individuals.
      Significant deformation and volume changes of the spinal canal can occur because
      of the vertebral slippage, but few data have been reported on these anatomic
      variations in DS patients. Whether to restore normal anatomy, such as reduction
      of the slippage and restoration of disc height, is still not clear in surgery.
      PURPOSE: This study was designed to determine the volume change of the spinal
      canal and detect specific anatomic factors affecting the spinal canal volume in
      DS patients. STUDY DESIGN/SETTING: A case-control study. METHODS: Nine
      asymptomatic volunteers (mean age 54.4) and 9 patients with L4/L5 DS (mean age
      73.4) were recruited. All patients had intermittent claudication and different
      extent low back pain, and two patients also had leg pain. L4/L5 vertebral motion
      segment unit of each subject was reconstructed using three-dimensional computed
      tomography or magnetic resonance images in a solid modeling software. In vivo
      lumbar vertebral motion during functional postures (supine, standing upright,
      flexion, and extension) was determined using a dual fluoroscopic imaging
      technique. The volume of the spinal canal was measured at each functional
      posture. Various anatomic parameters (disc height, cross-sectional area of the
      canal, left-right diameter of the canal, anterior-posterior diameter of the
      canal, slippage, posture, intervertebral disc angle [DA], etc.) that may
      potentially affect the canal volume were also measured, and their correlations
      with the volume change of spinal canal were analyzed. This study was funded by a
      2-year, $275,000 grant from the National Institutes of Health. RESULTS: On
      average, spinal canal volume was larger at supine and flexion postures than at
      stand and extension postures in both the DS and the asymptomatic groups. Spinal
      canal volume of the DS patients were significantly lower than that of the
      asymptomatic subjects under all the four postures (p<.05). Correlation analysis
      showed that spinal canal volume was strongly affected by the posterior disc
      height (Pearson correlation coefficient gammab=0.822) and the slippage percentage
      (gammab=-0.593) and moderately affected by the anterior disc height
      (gammab=0.300) and the DA (gammab=-0.237). CONCLUSIONS: The volume of spinal
      canal is affected by multiple factors. Increased spinal canal volume at supine
      and flexion positions may explain the clinical observations of relief of symptoms
      at these postures in DS patients. The data also suggest that reduction of slipped
      vertebral body, decrease of DA, intervertebral distraction, and decompression
      could all be effective to increase the canal volume of DS patients thus to
      relieve clinical symptoms.

PMID- 23541449
TI  - Unilateral, multilevel, interlaminar fenestration in the removal of a
      multisegment cervical intramedullary ependymoma.
AB  - BACKGROUND CONTEXT: Laminectomy is the traditional approach to intramedullary
      ependymomas and may lead to spinal instability and spinal deformities.
      Hemilaminectomy and laminoplasty have been developed to preserve the spinal
      stability and have been found to be effective. Unilateral, multilevel,
      interlaminar fenestration is another approach that may have more advantages in
      preserving the spinal stability; however, it has rarely been used by now.
      PURPOSE: Unilateral, multilevel, interlaminar fenestration was often used in the
      surgical treatment of degenerative lumbar stenosis; however, it was rarely used
      for tumors. The aim of this study was to discuss the characteristics and
      advantages of its use for a multisegment intramedullary ependymoma. STUDY DESIGN:
      Case report and literature review. METHODS: The 22-year-old man suffered from
      muscular atrophy of the left hand and the right hand for a period of 1.5 years
      and 3 months, respectively, and the cervical magnetic resonance imaging revealed
      an intramedullary mass of C4-C7. A right, unilateral, multilevel, interlaminar
      fenestration of the C3-C7 was performed with the help of high-speed air drills,
      and a midline myelotomy was made under microscope. The tumor was removed totally
      using piecemeal resection. RESULTS: The magnetic resonance imaging, obtained 1
      year after the operation, revealed that there were no residual mass lesion and no
      spinal instability, and the patient acquired an excellent functional outcome. So,
      this technique proved to be safe and easy in this case. CONCLUSIONS: Unilateral,
      multilevel, interlaminar fenestration allows good access to a long intraspinal
      segment, protects the structures essential to spinal stability as much as
      possible, preserves the spinal stability, and results in no additional injury to
      the spinal cord. It may be applicable to many other kinds of intraspinal tumors.

PMID- 23541450
TI  - Tuberculosis of the lower cervical spine (C5-C6) in a 24-month-old infant.
AB  - BACKGROUND: Tuberculosis (TB) of the cervical spine occurs rarely in younger
      children whereas the presentation and outcome are different from those of adult
      cervical spine. Because cervical spinal TB in younger children is rarely
      reported, the clinical characteristics, the treatments, and the expected outcome
      of treatments in younger children are still unknown. METHODS: We present a case
      of cervical spine TB in a 24-month-old boy that grounds severe vertebral
      destruction and an extradural abscess. This child presented with neurological
      deficit in the form of quadraparesis. We performed anterior cervical debridement
      for this patient; to our best knowledge, the child in this case is the youngest
      patient reported in the literature as having had cervical TB treated through
      anterior cervical surgery. RESULTS: The neurological deficits of this patient
      were recovered soon, and no evidence of recurrence of the tuberculous lesion or
      of the deformity was revealed by the 6-year follow-up magnetic resonance imaging.
      CONCLUSIONS: Based on our experiences in this case and a review of the
      literature, we propose that for patients of cervical spine TB in early childhood,
      anterior excision of diseased bone without grafting should be adequate as a
      surgical measure.

PMID- 23541451
TI  - Clinical features and surgical outcomes of patients with thoracic myelopathy
      caused by multilevel ossification of the ligamentum flavum.
AB  - BACKGROUND CONTEXT: Thoracic myelopathy caused by multilevel (three or more
      levels) ossification of the ligamentum flavum (OLF) is rare. Little is known
      about its clinical features, and the surgical outcomes along with its related
      factors are also unclear. PURPOSE: To describe the clinical features, assess the
      safety and effectiveness of surgical decompression, and determine the prognostic
      factors relevant for patients with thoracic myelopathy caused by multilevel OLF.
      STUDY DESIGN/SETTING: A retrospective clinical study. PATIENT SAMPLE: Seventy
      five consecutive multilevel OLF patients who underwent surgical decompression
      were analyzed. OUTCOME MEASURES: Modified Japanese Orthopedic Association (JOA)
      scale and the recovery rate. METHODS: Patients who underwent surgical
      decompression for symptomatic multilevel OLF during January 1996 to June 2010
      were all included. Clinical data were collected from medical and operative
      records; patients were evaluated by using the JOA scale preoperatively and during
      the follow-up. Correlations between the surgical outcome and various factors were
      also analyzed. RESULTS: Forty-three men and 32 women with a mean age of 54.7
      years (range 36-78 years) were included. The mean number of involved levels is
      4.6 and contiguous OLF presented in 73.3% of these patients. The most common
      involved levels were T10/T11 (15.4%), T9/T10 (13.3%), and T11/T12 (12.5%).
      Coexisting spinal disorders were found in 41 patients (54.7%). Preoperative
      evaluation showed the mean JOA score was 5.8+/-1.7; 37.3% of these patients had
      mild myelopathy, 53.3% had moderate myelopathy, and 9.3% had severe myelopathy.
      All patients received posterior laminectomy. The JOA score (mean 8.2+/-2.1)
      significantly increased postoperatively (p<.05), and multiple regression analysis
      showed that preoperative duration of symptoms and preoperative JOA score were
      important predictors of surgical outcome. CONCLUSIONS: Laminectomy with partially
      internal fixation is safe and effective in treatment of patients with symptomatic
      multilevel OLF. The results of our study show that preoperative JOA score and
      preoperative duration of symptoms were important predictors for the clinical
      outcome.

PMID- 23541452
TI  - Surgically treated cervical myelopathy: a functional outcome comparison study
      between multilevel anterior cervical decompression fusion with instrumentation
      and posterior laminoplasty.
AB  - BACKGROUND CONTEXT: Multilevel cervical myelopathy can be treated with anterior
      cervical discectomy and fusion (ACDF) or corpectomy via the anterior approach and
      laminoplasty via the posterior approach. Till date, there is no proven superior
      approach. PURPOSE: To elucidate any potential advantage of one approach over the
      other with regard to clinical midterm outcomes in this study. STUDY DESIGN: A
      prospective, 2-year follow-up of patients with cervical myelopathy treated with
      multilevel anterior cervical decompression fusion and plating and posterior
      laminoplasty. PATIENT SAMPLE: In total, 116 patients were studied. Sixty-four
      patients underwent ACDF two levels and above or anterior cervical corpectomy and
      fusion one level and above. Fifty-two patients underwent posterior cervical
      surgery (laminoplasty C3-C6 and C3-C7). OUTCOME MEASURES: Self-report measures:
      Japan Orthopedic Association (JOA) score, JOA recovery rate, visual analog scale
      for neck pain (VASNP), neck disability index (NDI), and American Academy of
      Orthopaedic Surgeons (AAOS) neurogenic symptom score (AAOS-NSS). Physiologic
      measures: range of motion (ROM) flexion and extension of neck. Functional
      measures: short-form 36 (SF-36) score comprising physical functioning, physical
      role function, bodily pain, general health, vitality, social role function,
      emotional role function, and mental health scales. METHODS: Comparison of the JOA
      scores, JOA recovery rates, NDI scores, SF-36 scores, VASNP, and ROM
      preoperatively to 2 years. Chi-square and two-sided Student t tests were used to
      analyze the variables. RESULTS: Posterior surgery took an hour shorter (p<.05)
      and had better improvement in JOA scores at early follow-up of 6 months (p=.025).
      Anterior surgery group had better improvement of NDI scores at early follow-up of
      6 months (p=.024) and was associated with less blood loss intraoperatively
      compared with posterior surgery. There was no statistical difference between the
      two groups for JOA scores, JOA recovery rates, SF-36 quality-of-life scores, NDI,
      AAOS-NSS, VAS neck pain, and ROM at 2 years. Complications were higher for
      anterior surgery group: two hematoma postoperation, one vocal cord paresis, and
      one new onset C6/C7 dermatome numbness versus one dura leak in posterior surgery
      group. CONCLUSIONS: Our study showed that patients with multilevel disease
      treated with laminoplasty do well and compare favorably with patients treated
      with an anterior approach. Notably, posterior surgery was associated with shorter
      operating time, better improvement in JOA scores at 6 months, and a tendency
      toward lesser complications. Posterior surgery was not associated with increased
      neck disability and neck pain at 2 years. Anterior surgery had better NDI
      improvement at early follow-up. There is a need for a larger study that is
      prospectively randomized with long-term follow-up before we can confidently
      advocate one approach over the other in the management of cervical myelopathy.

PMID- 23541453
TI  - The predisposing factors for the heterotopic ossification after cervical
      artificial disc replacement.
AB  - BACKGROUND CONTEXT: Heterotopic ossification (HO) is defined as a formation of
      bone outside the skeletal system. The reported HO occurrence rate in cervical
      artificial disc replacement (ADR) is unexpectedly high and is known to vary.
      However, the predisposing factors for HO in cervical ADR have not yet been
      elucidated. PURPOSE: Investigation of the predisposing factors of HO in cervical
      arthroplasty and the relationship between degeneration of the cervical spine and
      HO occurrence. STUDY DESIGN: Retrospective study to discover predisposing factors
      of HO in cervical arthroplasty. PATIENT SAMPLE: A total of 170 patients who
      underwent cervical ADR were enrolled including full follow-up clinical and
      radiologic data. OUTCOME MEASURES: Radiologic outcomes were assessed by
      identification of HOs according to McAfee's classifications. METHODS: This study
      enrolled a total of 170 patients who underwent cervical ADR. Pre-existing
      degenerative change included anterior or posterior osteophytes, ossification of
      the anterior longitudinal ligament, posterior longitudinal ligament, or
      ligamentum nuchae. The relationships between basic patient data, pre-existing
      degenerative change, and HO were investigated using linear logistic regression
      analysis. RESULTS: Among all 170 patients, HO was found in 69 patients (40.6%).
      Among the postulated predisposing factors, only male gender and artificial disc
      device type were shown to be statistically significant. Unexpectedly,
      preoperative degenerative changes in the cervical spine exerted no significant
      influence on the occurrence of HOs. The odds ratio of male gender compared with
      female gender was 2.117. With regard to device type, the odds ratios of Mobi-C
      (LDR medical, Troyes, France) and ProDisc-C (Synthes, Inc., West Chester, PA,
      USA) were 5.262 and 7.449, respectively, compared with the Bryan disc.
      CONCLUSIONS: Definite differences in occurrence rate according to the gender of
      patients and the prosthesis type were identified in this study. Moreover, factors
      indefinably expected to influence HO in the past were not shown to be risk
      factors thereof, the results of which may be meaningful to future studies.

PMID- 23541454
TI  - Is cervical lordosis relevant in laminoplasty?
AB  - BACKGROUND CONTEXT: Laminoplasty aims to decompress the spinal cord and stabilize
      the cervical spine in patients with multilevel cervical lesions. Not every
      patient with cervical compressive myelopathy is a good candidate for
      laminoplasty. Most studies recommend that neutral or kyphotic alignments are
      contraindications for laminoplasty. However, cervical sagittal alignment does not
      have a strong and consistent effect on the clinical outcomes of laminoplasty.
      Moreover, many reports on the effect of cervical sagittal alignment did not
      designate the ideal definition of alignment and used different definitions of
      lordosis. PURPOSE: To identify the effect of preoperative cervical alignment
      according to two different definitions after midline splitting double-door
      laminoplasty. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: From
      August 2008 to September 2010, 58 patients were diagnosed with cervical
      myelopathy and treated with midline splitting double-door laminoplasty. OUTCOME
      MEASURES: The clinical results were assessed with the modified Japanese
      Orthopedic Association (JOA) score, neck disability index (NDI), and visual
      analog scale (VAS) and were compared to analyze the rate of change between
      preoperative and postoperative values. Postoperative radiological results at the
      final follow-up examinations were compared between groups to obtain the change in
      range of motion and sagittal alignment. METHOD: The effect of cervical alignment
      on JOA, NDI, and VAS scales and also on change of alignment and change of range
      of motion (ROM) at the final follow-up examinations was analyzed statistically
      between two groups according to two different definitions such as Toyama
      classification and Cobb angle. RESULTS: No difference was found between the two
      groups according to Toyama classification in terms of the postoperative
      improvement rate of the modified JOA score (p=.086), decreasing rate of the VAS
      (p=.940) or NDI (p=.211), postoperatively. Additionally, no difference was found
      for the decreasing rate of ROM (p=.427) or sagittal alignment (p=.864) based on
      the radiological evaluation results. Also, there was no difference between two
      groups according to Cobb angle in terms of the modified JOA score (p=.743), VAS
      (p=.548), or NDI (p=.32), postoperatively. Additionally, no difference was found
      for the ROM (p=1.000) or sagittal alignment (p=.440) based on the radiological
      evaluation results. CONCLUSIONS: Despite nonlordosis cervical sagittal alignment,
      double-door laminoplasty would be effective for patients with cervical myelopathy
      because of cervical spondylotic myelopathy or ossification of the posterior
      longitudinal ligament. Furthermore, sagittal alignment is not the absolute and
      sole factor that surgeons should consider when determining the optimal treatment
      strategy.

PMID- 23541455
TI  - Complications associated with instrumented lumbar surgery in patients with liver
      cirrhosis: a matched cohort analysis.
AB  - BACKGROUND: There is no information in the English literature on the outcome of
      liver cirrhotic patients who have undergone instrumented lumbar surgery. PURPOSE:
      To review the results of instrumented lumbar surgery in patients with liver
      cirrhosis and determine the surgical risk factors in this group of patients.
      STUDY DESIGN: A retrospective study for comparison between two cohorts (liver
      cirrhosis vs. nonliver cirrhosis). PATIENT SAMPLE: Fifty-eight patients. OUTCOME
      MEASURES: Child-Turcotte-Pugh scale was used to assess the patients' hepatic
      functional reserve. The clinical outcomes were evaluated by the five-grade
      patient-centered general outcome assessment questionnaire. Any event that led to
      reoperation, requirement of intensive care, prolonging of the hospital stay (more
      than 14 days), or admission after discharge within 30 days of surgery was defined
      as a perioperative complication. METHODS: Between 1997 and 2009, patients with
      liver cirrhosis who had undergone instrumented lumbar surgeries for degenerative
      lumbar disease were studied. All data were compared with those for gender-, age-,
      and diagnosis-matched nonliver cirrhosis patients. RESULTS: Liver cirrhotic
      patients had significantly lower preoperative hemoglobin, white blood cell
      counts, platelets, and albumin levels and higher prothrombin time and bilirubin
      level. Instrumented lumbar surgery was associated with significantly more blood
      loss, a longer hospital stay, and more complications in patients with liver
      cirrhosis compared with control patients. The final satisfactory rate was higher
      in the control group but without statistical difference (85% vs. 65%, p=.240). In
      the cirrhotic group, 22 patients (76%) were Child Class A and 7 patients (24%)
      were Child Class B; 12 patients developed one or more complications. Patients
      with Child Class B had a significantly higher incidence of complications than
      those with Child Class A (p=.006). In patients with Child Class A, those with a
      score of 6 also had a significantly higher incidence of complications than those
      with a score of 5 (p<.001). Female gender (p=.035), a low level of albumin
      (p=.002), presence of ascites (p=.029), and increased blood loss (p=.044) were
      associated with a higher risk of complications. CONCLUSIONS: The rate of
      complications after instrumented lumbar surgery was significantly higher in
      patients with cirrhosis than in control patients, especially in those with 6 or
      more Child-Turcotte-Pugh points. The surgeon should counsel these patients on the
      possibility of developing early complications. Several factors were associated
      with surgical complications and should be addressed by the spine surgeons before
      or when they perform these elective instrumented lumbar surgeries.

PMID- 23541456
TI  - An unusual presentation of chest pain: needle perforation of the right ventricle.
AB  - Foreign bodies in the heart are a rare occurrence and can result from intravenous
      drug abuse, trauma or iatrogenic causes. There are no current guidelines for the
      treatment of a cardiac foreign body. We hereby present a brief review of the
      available literature and report a case of a woman with chest pain subsequently
      complicated by cardiogenic shock due to tamponade secondary to a needle fragment
      perforating her right ventricular free wall.

PMID- 23541457
TI  - A new risk classification system for therapeutic decision making with
      intermediate-risk prostate cancer patients undergoing dose-escalated external
      beam radiation therapy.
AB  - BACKGROUND: The management of intermediate-risk prostate cancer (PCa) is
      controversial, in part due to the heterogeneous nature of patients falling within
      this classification. OBJECTIVE: We propose a new risk stratification system for
      intermediate-risk PCa to aid in prognosis and therapeutic decision making.
      DESIGN, SETTING, AND PARTICIPANTS: Between 1992 and 2007, 1024 patients with
      National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy
      information were treated with definitive external-beam radiation therapy (EBRT)
      utilizing doses >= 81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as
      any intermediate-risk patient with a primary Gleason pattern of 4, percentage of
      positive biopsy cores (PPBC) >= 50%, or multiple intermediate-risk factors (IRFs;
      cT2b-c, prostate-specific antigen [PSA] 10-20, or Gleason score 7). INTERVENTION:
      All patients received EBRT with >= 81 Gy with or without neoadjuvant and
      concurrent androgen-deprivation therapy (ADT). OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Univariate and multivariate analyses were performed using a
      Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and
      distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a
      competing-risk method. RESULTS AND LIMITATIONS: Median follow-up was 71 mo.
      Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p<0.0001), PPBC >= 50% (HR:
      2.72; p=0.0007), and multiple IRFs (HR: 2.20; p=0.008) all were significant
      predictors of increased DM in multivariate analyses. Primary Gleason pattern 4
      (HR: 5.23; p<0.0001) and PPBC >= 50% (HR: 4.08; p=0.002) but not multiple IRFs
      (HR: 1.74; p=0.21) independently predicted for increased PCSM. Patients with UIR
      disease had inferior PSA-RFS (HR: 2.37; p<0.0001), DM (HR: 4.34; p=0.0003), and
      PCSM (HR: 7.39; p=0.007) compared with those with favorable intermediate-risk
      disease, despite being more likely to receive neoadjuvant ADT. Short follow-up
      and retrospective study design are the primary limitations. CONCLUSIONS:
      Intermediate-risk PCa is a heterogeneous collection of diseases that can be
      separated into favorable and unfavorable subsets. These groups likely will
      benefit from divergent therapeutic paradigms.

PMID- 23541458
TI  - Obesity is associated with increased prostate growth and attenuated prostate
      volume reduction by dutasteride.
AB  - BACKGROUND: Although obesity has been associated with larger prostate volumes
      (PV), few studies have actually investigated whether obesity enhances PV growth,
      especially among men using 5alpha-reductase inhibitors. OBJECTIVE: To examine
      whether obesity is associated with enhanced PV growth measured by serial
      transrectal ultrasound (TRUS) measurements. DESIGN, SETTING, AND PARTICIPANTS: We
      conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer
      Events (REDUCE) trial, which was originally aimed at cancer risk reduction among
      high-risk men with a single negative prestudy biopsy. INTERVENTION: Per-protocol
      randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2
      yr and 4 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Percentage change in
      PV at 2 yr and 4 yr from baseline. We tested its association with baseline body
      mass index (BMI) groups of <25, 25-29.9, and >= 30 kg/m(2) using multivariable
      linear regression. Secondarily, we tested whether BMI was associated with the
      likelihood of having no PV reduction among men randomized to dutasteride using
      multivariable logistic regression. RESULTS AND LIMITATIONS: Of 8122 participants,
      we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In
      multivariable analysis, men on placebo with BMI >= 30 versus < 25 kg/m(2) had
      enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p<0.001; at 4 yr:
      29.4% vs 20.1%; p=0.001). Men on dutasteride with BMI >= 30 versus < 25 kg/m(2)
      had attenuated PV reduction from baseline (at 2 yr: -14.3% vs -18.5%; p=0.002; at
      4 yr: -13.2% vs -19.3%; p=0.001) and higher likelihood of having no PV reduction
      (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08-1.93;
      p=0.014; at 4 yr: OR: 1.62; 95% CI, 1.18-2.22; p=0.003). We found no significant
      interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p
      interaction >= 0.36). No clinical outcomes or effects of weight change were
      assessed. CONCLUSIONS: Obesity enhanced PV growth and attenuated PV reduction by
      dutasteride. The null interaction between obesity and dutasteride for PV change
      implies that the effect of obesity on dutasteride-treated men is likely a
      combination of dutasteride-driven PV reduction with obesity-driven PV growth
      rather than decreased dutasteride efficacy.

PMID- 23541460
TI  - Is folic acid supplementation definitely beneficial to stroke prevention?:
      comment on: Efficacy of folic acid supplementation in cardiovascular disease
      prevention: an updated meta-analysis of randomized controlled trials.

PMID- 23541461
TI  - The origin and the evolution of hospitals: the case of Padua.

PMID- 23541462
TI  - Laboratory-based real and reciprocal space imaging of the electronic structure of
      few layer graphene on SiC(0001-) using photoelectron emission microscopy.
AB  - We present real and reciprocal space photoelectron emission microscopy (PEEM)
      results on few layer graphene using laboratory based He I and II radiation. The
      combination of a focused high-intensity source and high transmission PEEM
      electron optics provides good signal to noise ratios for the different modes of
      acquisition. We demonstrate work function mapping and secondary electron
      analysis, related to the graphene layer thickness, band structure imaging from
      micron scale regions by wave vector resolved PEEM (k-PEEM) and local secondary
      electron spectroscopy, giving information on the valence and conduction band
      states and the dispersion relations of the pi bands. Dark field PEEM is done by
      selecting the Dirac cone corresponding to the specific rotation of each graphene
      layer and allows spatial mapping of the commensurate rotation angles. The use of
      He II radiation increases the volume of reciprocal space accessible to k-PEEM and
      improves signal to background. The preferential linear polarization of the light
      source is used to investigate aspects of the electronic chirality near the Dirac
      cone. Recent developments in sample manipulation and cooling are presented. 

PMID- 23541463
TI  - Major changes in lung cancer over the last ten years in France: the KBP-CPHG
      studies.
AB  - The incidence of lung cancer has dramatically increased in ten years, being now
      the most commonly diagnosed cancer in males and the fourth most commonly
      diagnosed cancer in females. Considering social and scientific evolution, the aim
      of the present study conducted by the French College of General Hospital
      Respiratory Physicians (CPHG) was to compare patient and lung cancer
      characteristics at a ten-year interval. Two epidemiological studies, KBP-2000
      CPHG and KBP-2010-CPHG, were conducted at a ten-year interval. These prospective
      multicentre studies included all patients >= 18 years of age with primary lung
      cancer diagnosed between 1st January and 31st December 2000 or 2010, and managed
      in the respiratory departments of one of the participating general hospitals. A
      standardised form was completed for each patient. A steering committee checked
      recruitment exhaustiveness. Respectively, in 2000 and 2010, 137 and 104 centres
      included 5667 and 7051 patients. Compared to 2000, patients in 2010 were
      significantly older (65.5 +/- 11.3 vs. 64.3 +/- 11.5 years, p < 0.0001), more
      frequently women (24.3% vs. 16.0%, p < 0.0001) and never-smokers (10.9% vs. 7.2%,
      p < 0.0001). In 2010, adenocarcinoma was the most common tumour (45.4%, vs. 29.0%
      in 2000, p < 0.0001). The adenocarcinoma rate increased irrespective of sex, age,
      or smoking status (relative risk [RR] before and after adjustment, RR = 2.07
      [1.92-2.24], p < 0.0001 and 2.06 [1.90-2.23], p < 0.0001). In ten years, lung
      cancer characteristics have therefore changed: more women, more never-smokers,
      and more adenocarcinomas. The particular high increase in adenocarcinoma rate
      deserves further analysis.

PMID- 23541464
TI  - Molecular cloning and expression of the cDNA sequence encoding a novel aspartic
      protease from Uncinaria stenocephala.
AB  - Uncinaria stenocephala belongs to Ancylostomatidae family. Members of this family
      - hookworms - infect millions of people and animals worldwide. U. stenocephala is
      most pathogenic in dogs and other Canidae, which are the main hosts, and
      infection causes anemia or even death. So far no effective hookworm vaccine has
      been developed that is economically viable. Attempts to identify vaccine antigens
      have led to a group of aspartic proteases, which play a key role in parasite
      feeding, migration through host tissues and immune evasion. The cDNA of an
      aspartic protease from U. stenocephala was cloned using the RACE-PCR method.
      Computational analysis showed that the cDNA encodes a 447 amino acid protein with
      a molecular mass of 52kDa that shows high homology to aspartic proteases from
      related hookworms. Analysis identified 1 potential N-glycosylation site, 3
      potential disulfide bonds and no O-glycosylation sites. The recombinant protein
      was expressed in Escherichia coli followed by purification and mouse
      immunization. Using raised anti-Us-APR-1(2) (Uncinaria stenocephala Aspartic
      protease-1) serum the presence of Us-APR-1 in the adult stage of U. stenocephala
      and the expression of homologous protease in L3 and adult stages of A. ceylanicum
      was confirmed. This analysis is the first phase of work exploring the biological
      role of Us-APR-1 in parasite-host interactions and raises hope for successful
      vaccine development against Uncinaria sp. and possibly Ancylostoma sp.

PMID- 23541465
TI  - Molecular characterization of Echinococcus granulosus isolated from sheep in
      Palestine.
AB  - A total of twenty-three Echinococcus granulosus hydatid cysts were collected from
      infected sheep slaughtered in Nablus abattoir, Nablus - Palestine. Protoscoleces
      or germinal membranes were used for DNA extraction followed by PCR amplification.
      Amplified products were analyzed the presence of a fragment of 444bp of the
      mitochondrial cytochrome c oxidase subunit 1 (cox1) gene followed by nucleotide
      sequencing. Overall, 21 hydatid cysts were positive compared to a negative
      control. The partial sequences of cox1 gene of E. granulosus strains indicated
      that the sheep in Palestine were infected with genotype 1 (G1), genotype 2 (G2)
      and genotype 3 (G3). The prevalence of these genotypes was (14/21) 66.7%, (4/21)
      19.0% and (3/21) 14.3% for G1, G2 and G3, respectively. Our results showed that
      twelve strains of G1 belonged to the common haplotype EG01 which is the major
      haplotype in all the geographic populations. Phylogenetic analysis also showed
      that two sequences of G1 genotype which have GenBank accession No. KC109657 and
      KC109659 were corresponding to G1.4 micro-variants. Only the sequence of GenBank
      accession No. KC109652 identified in our study as G2 was found to have complete
      identity to the original sequence described for the cox1 gene (GenBank accession
      No. M84662). It is concluded that G1 genotype is the predominant genotype in
      sheep in Palestine. Therefore, these findings should be taken into consideration
      in developing prevention strategies and control programs for hydatidosis in
      Palestine.

PMID- 23541466
TI  - Phenol composition, cytotoxic and anti-kinetoplastidae activities of Lygodium
      venustum SW. (Lygodiaceae).
AB  - The search for new therapeutic agents has been a constant for the treatment of
      diseases such as leishmaniasis and Chagas disease. Most drugs used have side
      effects, justifying the need to evaluate the cytotoxicity of the tested products
      for candidates to new drugs. In this study, the bioactivity of Lygodium venustum,
      a cosmopolitan fern of Lygodiaceae, was assessed about their leishmanicidal and
      trypanocidal potential. The better activity was observed using methanol fraction,
      with inhibition percentage of 63% and 68% for promastigotes and epimastigotes,
      respectively, at a concentration of 500 MUg/mL. The ethyl acetate and methanol
      fractions demonstrated a higher cytotoxic potential. This was the first report of
      leishmanicidal, trypanocidal and cytotoxic activities to L. venustum.

PMID- 23541467
TI  - Post-transcriptional gene silencing of the gene encoding aldolase from soybean
      cyst nematode by transformed soybean roots.
AB  - Plant parasitic nematodes cause approximately 157 billion US dollars in losses
      worldwide annually. The soybean cyst nematode (SCN), Heterodera glycines, is
      responsible for an estimated one billion dollars in losses to the US farmer each
      year. A promising new approach for control of plant parasitic nematode control is
      gene silencing. We tested this approach by silencing the SCN gene HgALD, encoding
      fructose-1,6-diphosphate aldolase. This enzyme is important in the conversion of
      glucose into energy and may be especially important in actin-based motility
      during parasite invasion of its host. An RNAi construct targeted to silence HgALD
      was transformed into soybean roots of composite plants to examine its efficacy to
      reduce the development of females formed by SCN. The number of mature females on
      roots transformed with the RNAi construct designed to silence the HgALD gene was
      reduced by 58%. These results indicate that silencing the aldolase gene of SCN
      +can greatly decrease the number of female SCN reaching maturity, and it is a
      promising step towards broadening resistance of plants against plant-parasitic
      nematodes.

PMID- 23541468
TI  - Measuring the temporal extension of the Now.
AB  - Anticipatory systems require a model of time which takes account of both
      successive and simultaneous rhythms. Such a model should also incorporate the
      fact that both past and future determine the present state of anticipatory
      systems across multiple scales, from physical to biological and social ones. My
      Theory of Fractal Time meets these requirements and enables us to compare the
      Now's temporal complexity of endo-observer-participants in terms of their
      boundary complexity. 

PMID- 23541469
TI  - Crisis in science: in search for new theoretical foundations.
AB  - Recognition of the need for theoretical biology more than half century ago did
      not bring substantial progress in this direction. Recently, the need for new
      methods in science, including physics became clear. The breakthrough should be
      sought in answering the question "What is life?", which can help to explain the
      mechanisms of consciousness and consequently give insight into the way we
      comprehend reality. This could help in the search for new methods in the study of
      both physical and biological phenomena. However, to achieve this, new theoretical
      discipline will have to be developed with a very general conceptual framework and
      rigor of mathematical reasoning, allowing it to assume the leading role in
      science. Since its foundations are in the recognition of the role of life and
      consciousness in the epistemic process, it could be called biomathics. The prime
      candidates proposed here for being the fundamental concepts for biomathics are
      'information' and 'information integration', with an appropriately general
      mathematical formalism. 

PMID- 23541471
TI  - Gain modulation of the middle latency cutaneous reflex in patients with chronic
      joint instability after ankle sprain.
AB  - OBJECTIVE: To investigate the neural alteration of reflex pathways arising from
      cutaneous afferents in patients with chronic ankle instability. METHODS:
      Cutaneous reflexes were elicited by applying non-noxious electrical stimulation
      to the sural nerve of subjects with chronic ankle instability (n=17) and control
      subjects (n=17) while sitting. Electromyographic (EMG) signals were recorded from
      each ankle and thigh muscle. The middle latency response (MLR; latency: 70-120
      ms) component was analyzed. RESULTS: In the peroneus longus (PL) and vastus
      lateralis (VL) muscles, linear regression analyses between the magnitude of the
      inhibitory MLR and background EMG activity showed that, compared to the uninjured
      side and the control subjects, the gain of the suppressive MLR was increased in
      the injured side. This was also confirmed by the pooled data for both groups. The
      degree of MLR alteration was significantly correlated to that of chronic ankle
      instability in the PL. CONCLUSIONS: The excitability of middle latency cutaneous
      reflexes in the PL and VL is modulated in subjects with chronic ankle
      instability. SIGNIFICANCE: Cutaneous reflexes may be potential tools to
      investigate the pathological state of the neural system that controls the lower
      limbs in subjects with chronic ankle instability.

PMID- 23541472
TI  - Effects of exposure to amitraz on noradrenaline, serotonin and dopamine levels in
      brain regions of 30 and 60 days old male rats.
AB  - The effects of amitraz oral exposure (20, 50 and 80mg/kg bw, 5 days) on brain
      region monoamine levels of male rats at 30 and 60 days of age were examined. The
      amitraz-treated rats at the oral doses of 20 and 50mg/kg bw had no visible
      injury, i.e., any clinical signs of dysfunction observed in any of the animals.
      However, rats treated with amitraz at the highest dose (80mg/kg bw, 5 days)
      showed a slight motor incoordination after 1-2h of treatment. These signs were
      reversible approximately at 6h after dose. After the last dose of amitraz, NE, DA
      and 5-HT and its metabolites levels were determined in the brain regions
      hypothalamus, midbrain, prefrontal cortex, striatum and hippocampus by HPLC.
      Amitraz caused changes in the NE, DA and 5-HT and their metabolite levels in a
      brain regional-, dose- and age-related manner. In the brain regions studied,
      amitraz induced a statistically significant increase in 5-HT, NE and DA content
      with age interaction, but the NE increases in prefrontal cortex and hippocampus
      was without age interaction. Moreover, in the brain regions studied, amitraz
      induced a statistically significant decrease in the metabolite 5-HIAA, MHPG,
      DOPAC and HVA levels displaying an age interaction, excepting the 5-HIAA decrease
      in midbrain and the DOPAC decrease in hypothalamus and striatum which were
      without age interaction. Furthermore, amitraz evoked a statistically significant
      decrease in 5-HT, NE and DA turnover in the brain regions studied. The present
      findings indicate that amitraz significantly altered CNS monoaminergic
      neurotransmitters in a brain regional-, dose- and age-related manner.

PMID- 23541470
TI  - Nutritional protective mechanisms against gut inflammation.
AB  - Inflammatory bowel disease (IBD) is a debilitating and widespread immune-mediated
      illness characterized by excessive inflammatory and effector mucosal responses
      leading to tissue destruction at the gastrointestinal tract. Interactions among
      the immune system, the commensal microbiota and the host genotype are thought to
      underlie the pathogenesis of IBD. However, the precise etiology of IBD remains
      unknown. Diet-induced changes in the composition of the gut microbiome can
      modulate the induction of regulatory versus effector immune responses at the gut
      mucosa and improve health outcomes. Therefore, manipulation of gut microbiota
      composition and the local production of microbial-derived metabolites by using
      prebiotics, probiotics and dietary fibers is being explored as a promising avenue
      of prophylactic and therapeutic intervention against gut inflammation. Prebiotics
      and fiber carbohydrates are fermented by resident microflora into short chain
      fatty acids (SCFAs) in the colon. SCFAs then activate peroxisome proliferator
      activated receptor (PPAR)gamma, a nuclear transcription factor with widely
      demonstrated anti-inflammatory efficacy in experimental IBD. The activation of
      PPARgamma by naturally ocurring compounds such as conjugated linoleic acid,
      pomegranate seed oil-derived punicic acid, eleostearic acid and abscisic acid has
      been explored as nutritional interventions that suppress colitis by directly
      modulating the host immune response. The aim of this review is to summarize the
      status of innovative nutritional interventions against gastrointestinal
      inflammation, their proposed mechanisms of action, preclinical and clinical
      efficacy as well as bioinformatics and computational modeling approaches that
      accelerate discovery in nutritional and mucosal immunology research.

PMID- 23541473
TI  - Generic and functional diversity in endophytic actinomycetes from wild Compositae
      plant species at South Sinai - Egypt.
AB  - The diversity of culturable endophytic actinomycetes associated with wild
      Compositae plants is scantily explored. In this study, one hundred and thirty one
      endophytic actinobacteria were isolated from ten Compositae plant species
      collected from South Sinai in Egypt. Microscopic and chemotaxonomic investigation
      of the isolates indicated fourteen genera. Rare genera, such as Microtetraspora,
      and Intrasporangium, which have never been previously reported to be endophytic,
      were identified. Each plant species accommodated between three to eight genera of
      actinobacteria and unidentified strains were recovered from seven plant species.
      The generic diversity analysis of endophytic assemblages grouped the plant
      species into three main clusters, representing high, moderate and low endophytic
      diversity. The endophytes showed high functional diversity, based on forty four
      catabolic and plant growth promotion traits; providing some evidence that such
      traits could represent key criteria for successful residence of endophytes in the
      endosphere. Stress-tolerance traits were more predictive measure of functional
      diversity differences between the endophyte assemblages (Shannon's index, p =
      0.01). The results indicate a potential prominent role of endophytes for their
      hosts and emphasize the potency of plant endosphere as a habitat for
      actinobacteria with promising future applications.

PMID- 23541474
TI  - Type I secretion systems - a story of appendices.
AB  - Secretion is an essential task for prokaryotic organisms to interact with their
      surrounding environment. In particular, the production of extracellular proteins
      and peptides is important for many aspects of an organism's survival and
      adaptation to its ecological niche. In Gram-negative bacteria, six different
      protein secretion systems have been identified so far, named Type I to Type VI;
      differing greatly in their composition and mechanism of action (Economou et al.,
      2006). The two membranes present in Gram-negative bacteria are negotiated either
      by one-step transport mechanisms (Type I and Type III), where the unfolded
      substrate is translocated directly into the extracellular space, without any
      periplasmic intermediates, or by two-step mechanisms (Type II and Type V), where
      the substrate is first transported into the periplasm to allow folding before a
      second transport step across the outer membrane occurs. Here we focus on Type I
      secretion systems and summarise our current knowledge of these one-step transport
      machineries with emphasis on the N-terminal extensions found in many Type I
      specific ABC transporters. ABC transporters containing an N-terminal C39
      peptidase domain cut off a leader peptide present in the substrate prior to
      secretion. The function of the second type of appendix, the C39 peptidase-like
      domain (CLD), is not yet completely understood. Recent results have shown that it
      is nonetheless essential for secretion and interacts specifically with the
      substrate of the transporter. The third group present does not contain any
      appendix. In light of this difference we compare the function of the appendix and
      the differences that might exist among the three families of T1SS.

PMID- 23541475
TI  - Assembly of the type II secretion system.
AB  - The type II secretion system is utilized by many Gram-negative bacteria to export
      folded proteins to the surface and/or the extracellular environment of the cell.
      Although the function of the system is to move proteins from the periplasm to the
      outside of the cell, it is a large trans-envelope structure composed of more than
      a dozen different proteins present in multiple copies, including peripheral,
      integral inner membrane and integral outer membrane proteins plus a pseudopilus
      stretching between them. The establishment of this structure as an integral
      component of the entire envelope including the peptidoglycan layer between the
      two membranes requires assembly. Many of the participants and processes involved
      in this assembly have now been established, while other aspects remain to be
      discovered or more fully understood. 

PMID- 23541476
TI  - Biotechnological applications of bacterial protein secretion: from therapeutics
      to biofuel production.
AB  - Recent years have witnessed significant progresses in engineering of recombinant
      protein secretion. The relatively simple secretion mechanisms, Type I and Type V
      (autotransporters), are increasingly used for secretion of recombinant proteins.
      The secretion level of target proteins varied from milligrams to grams per liter.
      The range of proteins was significantly expanded beyond medical application.
      Notable additions include biofuel productions from renewable feedstock. Despite
      the progress, almost all successes in the engineering efforts come with
      significant trials and errors, highlighting the need for a better understanding
      of secretion systems and rational based methods. 

PMID- 23541477
TI  - Leaving home ain't easy: protein export systems in Gram-positive bacteria.
AB  - Transport of proteins into or across biological membranes is catalyzed by
      membrane-bound transport machineries. In Gram-positive bacteria, the vast
      majority of proteins are exported out of the cytosol by the conserved general
      secretion (Sec) system or, alternatively, by the twin-arginine translocation
      (Tat) system, that closely resemble their well-studied counterparts in Gram
      negative bacteria. Besides these common major export routes, additional unique
      protein export systems (such as accessory Sec2 systems and/or type VII/WXG100
      secretion systems) exist in some Gram-positive bacteria that are specifically
      involved in the secretion of limited subsets of proteins.

PMID- 23541478
TI  - Structural basis of eukaryotic cell targeting by type III secretion system (T3SS)
      effectors.
AB  - Type III secretion systems (T3SS) are macromolecular complexes that translocate a
      wide number of effector proteins into eukaryotic host cells. Once within the
      cytoplasm, many T3SS effectors mimic the structure and/or function of eukaryotic
      proteins in order to manipulate signaling cascades, and thus play pivotal roles
      in colonization, invasion, survival and virulence. Structural biology techniques
      have played key roles in the unraveling of bacterial strategies employed for
      mimicry and targeting. This review provides an overall view of our current
      understanding of structure and function of T3SS effectors, as well as of the
      different classes of eukaryotic proteins that are targeted and the consequences
      for the infected cell.

PMID- 23541479
TI  - Hepatocellular carcinoma likelihood on MRI exams: evaluation of a standardized
      categorization system.
AB  - PURPOSE: Evaluate the reliability and validity of a standardized reporting system
      designed to improve communication between the clinician and radiologist regarding
      likelihood of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The system
      assigns liver lesions into 1 of 5 categories of estimated likelihood of HCC: 1,
      <5%; 2, 5%-20%; 3, 21%-70%; 4, 71%-95%; 5, >95%. Six American Board of Radiology
      certified radiologists reviewed 100 abdominal MRI studies (performed between
      September 2009 and June 2010 for HCC surveillance) blinded to the official
      reports and clinical information. Each reader recorded the highest category (1-5)
      assigned to any lesion per study. Reliability between readers was calculated by
      the Shrout-Fliess random sets intraclass correlation (ICC). To examine validity,
      original pretransplant reports from January 2009 to December 2010 were compared
      to pathology reports on liver explants. Sensitivities, specificities, predictive
      values, and receiver operating characteristic (ROC) curves were then produced.
      RESULTS: The ICC for retrospective readings was 0.80, indicating very good
      reliability. Of 45 pathologically proven cases, 16 category 1 or 2 cases were all
      free of HCC (negative predictive value 100%). Five of nine category 3 cases
      contained HCC. Six of eight category 4 cases contained HCC (PPV 75%). All 12
      category 5 cases contained HCC (positive predictive value 100%). The area
      underneath the ROC curve was 0.949. If categories 1 and 2 are considered negative
      and categories 3-5 considered positive, this achieves 100% sensitivity with 73%
      specificity. CONCLUSION: This standardized system for reporting likelihood of
      HCC, which is a forerunner of the recently introduced Liver Imaging Reporting and
      Data System, produces strong reliability and validity, while aiming to improve
      the clarity of clinical magnetic resonance imaging reports.

PMID- 23541480
TI  - High-dose-rate strictures: a theory of cancer meets anatomic reality.

PMID- 23541481
TI  - Assessment of intracellular cytokines and regulatory cells in patients with
      autoimmune diseases and primary immunodeficiencies - novel tool for diagnostics
      and patient follow-up.
AB  - Serum and intracytoplasmic cytokines are mandatory in host defense against
      microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases
      by initiating and perpetuating various cellular and humoral autoimmune processes.
      The intricate interplay and fine balance of pro- and anti-inflammatory processes
      drive, whether inflammation and eventually organ damage will occur, or the
      inflammatory cascade quenches. In the early and late, as well as inactive and
      active stages of autoimmune diseases, different cellular and molecular patterns
      can dominate in these patients. However, the simultaneous assessment of pro- and
      anti-inflammatory biomarkers aids to define the immunological state of a patient.
      A group of the most useful inflammatory biomarkers are cytokines, and with
      increasing knowledge during the last decade their role have been well-defined in
      patients with autoimmune diseases and immunodeficiencies. Multiple pathological
      processes drive the development of autoimmunity and immunodeficiencies, most of
      which involve quantitative and qualitative disturbances in regulatory cells,
      cytokine synthesis and signaling pathways. The assessment of these biomarkers
      does not aid only in the mechanistic description of autoimmune diseases and
      immunodeficiencies, but further helps to subcategorize diseases and to evaluate
      therapy responses. Here, we provide an overview, how monitoring of cytokines and
      regulatory cells aid in the diagnosis and follow-up of patients with autoimmune
      diseases and immunodeficiencies furthermore, we pinpoint novel cellular and
      molecular diagnostic possibilities in these diseases. 

PMID- 23541482
TI  - Cardiovascular disease in autoimmune rheumatic diseases.
AB  - Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis,
      spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated
      with premature atherosclerosis. However, premature atherosclerosis has not been
      uniformly observed in systemic sclerosis. Furthermore, although experimental
      models of atherosclerosis support the role of antiphospholipid antibodies in
      atherosclerosis, there is no clear evidence of premature atherosclerosis in
      antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be
      caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular
      disease (CVD) in ARDs is caused by traditional and non-traditional risk factors.
      Besides other factors, inflammation and immunologic abnormalities, the quantity
      and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia,
      obesity and underweight, presence of platelets bearing complement protein C4d,
      reduced number and function of endothelial progenitor cells, apoptosis of
      endothelial cells, epigenetic mechanisms, renal disease, periodontal disease,
      depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency
      may contribute to the premature CVD. Although most research has focused on
      systemic inflammation, vascular inflammation may play a crucial role in the
      premature CVD in ARDs. It may be involved in the development and destabilization
      of both atherosclerotic lesions and of aortic aneurysms (a known complication of
      ARDs). Inflammation in subintimal vascular and perivascular layers appears to
      frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients.
      It is possible that this inflammation is caused by infections and/or
      autoimmunity, which might have consequences for treatment. Importantly, drugs
      targeting immunologic factors participating in the subintimal inflammation (e.g.,
      T- and B-cells) might have a protective effect on CVD. Interestingly, vasa
      vasorum and cardiovascular adipose tissue may play an important role in
      atherogenesis. Inflammation and complement depositions in the vessel wall are
      likely to contribute to vascular stiffness. Based on biopsy findings, also
      inflammation in the myocardium and small vessels may contribute to premature CVD
      in ARDs (cardiac ischemia and heart failure). There is an enormous need for an
      improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics
      on vascular inflammation and CV risk are warranted. 

PMID- 23541483
TI  - A literature review on optic neuritis following vaccination against virus
      infections.
AB  - Optic neuritis (ON) is a primary inflammation of the optic nerve. ON is mostly
      idiopathic, and infrequently occurs on the background of systemic autoimmune
      disease, recent infectious disease or inoculation with mostly adjuvanted
      vaccines. Published case histories, retrospective reviews and analyses of
      epidemiological data report on the onset of immune-mediated ON (and other
      autoimmune disorders) within a defined period (days to weeks) after immunization
      of patients with probable genetic predisposition. After vaccination, there exists
      no long-term increased risk to develop ON. The risk for these vaccine-induced
      adverse events may be enhanced by adjuvants. Patient age distribution reflected
      immunization schedules and advisories, or patient age groups studied. Vaccination
      is one of the most important prevention tools in modern medicine, and a
      discussion on risk-benefit or cost-benefit analysis, and advisory on individual
      vaccines or vaccination programs falls outside the scope of this review. Despite
      a great deal of scientific uncertainty, the existence of a possible causal link
      between vaccines and acute ON should not be totally disregarded. 

PMID- 23541484
TI  - Making collaborative self-management successful in COPD patients with high
      disease burden.
AB  - BACKGROUND: Exacerbations in severe COPD patients lead to challenges in terms of
      self-management. This study is a "real-life" situation aiming to assess whether
      or not it is possible for COPD patients with high burden of disease to self
      manage acute exacerbations and to reduce hospital use. METHODS: 100 randomly
      selected charts of patients followed in a specialised COPD clinic in 2006 and
      2009 (patients with higher burden of disease) were reviewed. Data on patients'
      characteristics, COPD severity and exacerbation management were extracted.
      RESULTS: Compared to the 2006 cohort, patients from the 2009 cohort had lower
      (0.85 L), but not statistically significant different FEV1 (L) than the 2006
      cohort (0.98 L) and more exacerbations (2.6 exacerbations/pt vs 3. 6
      exacerbations/pt, p = 0.03). Despite having a higher burden of disease, patients
      in the 2009 cohort as compared to 2006 had more appropriate self-management
      behaviours in the event of an exacerbation (60% vs 42%, p = 0.05) and fewer
      emergency room visits and/or hospital admissions (39% vs 57%, p = 0.02). There
      were more phone calls to the case managers (590 vs 382, p < 0.001) and fewer
      physician office visits (167 vs 179, p = 0.024). CONCLUSIONS: This study of a
      real life situation adds to the current body of literature that a more severe
      COPD patient population can be taught self-management skills in the event of
      exacerbations, leading to fewer health care visits and hospital admissions.

PMID- 23541485
TI  - Coping styles in patients with COPD before and after pulmonary rehabilitation.
AB  - INTRODUCTION: Pulmonary rehabilitation (PR) improves physical and psychological
      symptoms in COPD patients. Patients' coping with daily symptoms and limitations
      may have more influence on important patient-centred outcomes than the impaired
      lung function. To date, it remains unknown whether and to what extent coping
      styles change following PR, and whether coping styles are associated with the
      outcomes of a comprehensive PR. METHODS: Coping styles were assessed in 303 COPD
      patients before and after a PR programme using the Utrecht Coping List (UCL).
      Additionally, lung function, St. George's Respiratory Questionnaire (SGRQ),
      Hospital Anxiety and Depression Scale, anxiety (HADS-A) and depression (HADS-D)
      subscales and six-minute walking distance (6MWD) were recorded. RESULTS: The
      level of active confronting coping style increased (p < 0.05), whereas the levels
      of avoidance (p < 0.05), passive reaction pattern and reassuring thoughts coping
      styles decreased following PR (both p < 0.001). More than 50% of the patients
      changed their level of active confronting, passive reaction pattern or expressing
      emotions coping style. Coping styles and/or changes in coping styles after PR
      were related to changes in exercise tolerance, anxiety and depression, but were
      not related to changes in health status. Following PR, SGRQ total score, HADS-A
      and HADS-D scores decreased (all p < 0.001), while 6MWD increased (p < 0.05).
      CONCLUSION: Comprehensive PR results in change in coping styles of COPD patients.
      Coping styles are related to improvements in exercise tolerance, anxiety and
      depression, but they are not related with changes in health status after PR.
      Further studies are needed to evaluate the outcome of interventions actively
      targeting coping styles.

PMID- 23541486
TI  - Religious involvement in major depression: protective or risky behavior? The
      relevance of bipolar spectrum.
AB  - BACKGROUND: Religiosity has been reported to be inversely related to depression
      and to suicide as well, but there is a lack of studies on its impact on bipolar
      disorder and especially, on depressed patients belonging to the bipolar spectrum.
      METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive
      DSM-IV major depressive patients evaluated in at least two semi-structured
      interviews 1 month apart, 234 (55.2%) could be classified as with high religious
      involvement (HRI), and 190 (44.8%) as with low religious involvement (LRI), on
      the basis of their ratings on the Duke Religious Index (DRI). RESULTS: Compared
      to LRI, HRI patients did not differ with respect to their religious affiliation
      but had a later age at onset of their affective illness with more
      hospitalizations, suicide attempts, associated hypomanic features, switches under
      antidepressant treatment, prescription of tricyclics, comorbid obsessive
      compulsive disorder, and family history of affective disorder in first-degree
      relatives. The following independent variables were associated with religious
      involvement: age, depressive temperament, mixed polarity of first episode, and
      chronic depression. The clinical picture of depressive patients with HRI was
      evocative of chronic mixed depressive episodes described in bipolar III patients
      within the spectrum of bipolar disorders. LIMITATIONS: Retrospective design,
      recall bias, lack of sample homogeneity, no assessment of potential protective
      and risk factors, and not representative for all religious affiliations.
      CONCLUSIONS: In depressive patients belonging to the bipolar spectrum, high
      religious involvement associated with mixed features may increase the risk of
      suicidal behavior, despite the existence of religious affiliation.

PMID- 23541487
TI  - Measuring depression in South Korea: validity and reliability of a brief
      questionnaire in the Korean Cancer Prevention Study.
AB  - OBJECTIVE: To examine the validity and reliability of a new questionnaire for
      measuring depression in a South Korean population, and then to estimate the
      prevalence of depression in that country using this tool. METHODS: In total,
      742,600 individuals (123,725 women), aged 30-64 years at entry into the Korean
      Cancer Prevention Study, completed a depression symptom in 1992 (baseline
      enrollment) and again in 1994. We examined the concurrent validity of the
      depression questionnaire by relating data from it to known socio-demographic and
      behavioral correlates of depression; its predictive capacity by relating scores
      from the questionnaire to the occurrence of future hospitalization for
      depression; and the test-retest reliability by comparing scores from its
      administration in 1992 to those in 1994. RESULTS: The prevalence of major
      depression was 7.5% in men and 10.0% in women. Factors significantly related to
      major depression were being younger (men), being female, not being married, of
      lower socioeconomic status, being a smoker, a heavy drinker, and not exercising
      regularly. Men (hazard ratio; 95% confidence interval: 2.0; 1.8, 2.2) and women
      (1.6; 1.3, 1.9) with questionnaire-ascertained depression experienced an elevated
      risk of hospitalization for the disorder during follow-up. The rates of agreement
      between responses to 1992 and 1994 surveys were 91.3% in men and 88.3% in women.
      CONCLUSIONS: These findings imply validity of the instrument and support its use
      in future studies directed at links of depression with somatic disease endpoints.
      LIMITATION: The questions do not have a specified time frame of reference.

PMID- 23541488
TI  - Biomarkers for non-human primate type-I hypersensitivity: antigen-specific
      immunoglobulin E assays.
AB  - Immunoglobulin E (IgE) is the least abundant immunoglobulin in serum. However,
      development of an IgE immune response can induce IgE receptor-expressing cells to
      carry out potent effector functions. A reliable antigen-specific IgE biomarker
      method for use in non-human primate studies would facilitate (i) confirmation of
      Type-I hypersensitivity reactions during safety toxicology testing, and (ii) a
      better understanding of non-human primate models of allergic disease. We cloned
      and expressed a recombinant cynomolgus monkey IgE molecule in order to screen a
      panel of commercially available detection reagents raised against human IgE for
      cross-reactivity. The reagent most reactive to cynomolgus IgE was confirmed to be
      specific for IgE and did not bind recombinant cynomolgus monkey IgG1-4. A drug
      specific IgE assay was developed on the MSD electrochemiluminescent (ECL)
      platform. The assay is capable of detecting 10 ng/mL drug-specific IgE.
      Importantly, the assay is able to detect IgE in the presence of excess IgG, the
      scenario likely to be present in a safety toxicology study. Using our ECL assay,
      we were able to confirm that serum from cynomolgus monkeys that had experienced
      clinical symptoms consistent with hypersensitivity responses contained IgE
      specific for a candidate therapeutic antibody. In addition, a bioassay for mast
      cell activation was developed using CD34(+)-derived cynomolgus monkey mast cells.
      This assay confirmed that plasma from animals identified as positive in the drug
      specific IgE immunoassay contained biologically active IgE (i.e. could sensitize
      cultured mast cells), resulting in histamine release after exposure to the
      therapeutic antibody. These sensitive assays for Type-I hypersensitivity in the
      NHP can confirm that secondary events are downstream of immunogenicity.

PMID- 23541489
TI  - Novel data analysis methods to overcome cut point challenges and enable
      comprehensive assessment of antidrug binding activity in confirmatory assays.
AB  - Immunogenicity assessments in response to drug treatment are commonly performed
      using a tiered approach strategy. All samples are initially tested in a screening
      assay followed by the evaluation of the screened positive samples in a
      confirmatory assay. Percent inhibition of signal intensity by the competing
      unlabeled drug in a confirmatory assay is typically used to measure the
      specificity of antidrug binding activity in samples, and has been successfully
      applied to most immunogenicity assays. However, the percent inhibition approach
      may not be suitable in cases where broadly distributed and high percent
      inhibition values are observed in drug-naive subjects or when persistent operator
      dependent differences in assay performance are encountered. Herein, we present
      the case studies faced with such challenges and provide appropriate solutions by
      introducing two novel data analysis methods: (1) Reference Delta, and (2)
      Reference Percent Inhibition, - in which relative-to-baseline signal inhibition
      is calculated for each sample. These novel methods significantly improve the
      confirmatory assay's ability to detect the samples positive for antidrug
      antibodies (ADA), especially when challenges are encountered using the
      traditional percent inhibition approach. Furthermore, both methods can be
      implemented in parallel with the percent inhibition method, enabling not only
      confirmation of ADA specificity, but also providing additional insights about the
      relevance of this antidrug binding activity to drug treatment.

PMID- 23541490
TI  - Cardiotrophin-1 (CTF1) ameliorates glucose-uptake defects and improves memory and
      learning deficits in a transgenic mouse model of Alzheimer's disease.
AB  - Cardiotrophin-1 (CTF1) has been reported to act as a trophic factor for a few
      neurons, such as sensory, cholinergic, dopaminergic, motor and cortical neurons.
      Studies have indicated that CTF1 delays degenerative disease progression in motor
      neuron disease. However, little is known about the effects of CTF1 on
      degenerative disease in the brain. We have shown that expression of CTF1 is
      strongly down-regulated in the brain of the APPswe/PS1dE9 transgenic mouse model
      of Alzheimer's disease (AD). Transgenic mice with brain tissue-specific CTF1
      expression alone or in combination with APPswe/PS1dE9 transgenic mice were
      produced to study the effects of CTF1 on AD. CTF1 expressing APPswe/PS1dE9
      transgenic mice exhibited improvements in learning and memory, less severe
      abnormalities in locomotor activity, reduced scattered senile plaques and
      ameliorated disturbances of brain energy metabolism compared to APPswe/PS1dE9
      transgenic mice. Furthermore, CTF1 inhibited the activity of glycogen synthase
      kinase-3beta (GSK-3beta) in SH-SY5Y cell line and in the brain tissues of
      APPswe/PS1dE9 transgenic mice. The transgenic expression of CTF1 compensated for
      the loss of CTF1 expression and brought about a marked improvement on cognitive
      functioning in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease,
      suggesting that the inhibition of GSK-3beta activity might play an important
      role.

PMID- 23541491
TI  - Anti-amnesic effect of pseudoginsenoside-F11 in two mouse models of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized
      by amyloid beta (Abeta) deposits, elevated oxidative stress, and apoptosis of the
      neurons. Pseudoginsenoside-F11 (PF11), a component of Panax quinquefolium
      (American ginseng), has been demonstrated to antagonize the learning and memory
      deficits induced by scopolamine, morphine and methamphetamine in mice. In the
      present study, we investigated the effect of PF11 on AD-like cognitive impairment
      both in mice induced by intracerebroventricular injection of Abeta1-42 (410 pmol)
      and in Tg-APPswe/PS1dE9 (APP/PS1) mice. It was found that oral treatment with
      PF11 significantly mitigated learning and memory impairment in mice given Abeta1
      42-treated mice for 15 days at doses of 1.6 and 8 mg/kg and APP/PS1 for 4 weeks
      at a dose of 8 mg/kg as measured by the Morris water maze and step-through tests.
      In APP/PS1 mice, PF11 8 mg/kg significantly inhibited the expressions of beta
      amyloid precursor protein (APP) and Abeta1-40 in the cortex and hippocampus,
      restored the activities of superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px) and decreased the production of malondialdehyde (MDA) in the cortex. It
      also noticeably improved the histopathological changes in the cortex and
      hippocampus and downregulated the expressions of JNK 2, p53 and cleaved caspase 3
      in the hippocampus. These findings suggested that the inhibitory effect on
      amyloidogenesis and oxidative stress and some beneficial effects on neuronal
      functions might contribute to the recognition improvement effect of PF11 in
      APP/PS1 mice. Cumulatively, the present study indicated that PF11 may serve as a
      potential therapeutic agent for the treatment of AD.

PMID- 23541492
TI  - Quercetin alleviates predator stress-induced anxiety-like and brain oxidative
      signs in pregnant rats and immune count disturbance in their offspring.
AB  - This study was performed in rats to investigate the effect of a psychogenic
      stress during late gestation on the immediate behavior and brain oxidative status
      in dams as well as on the immune cell counts in their offspring up to weaning.
      Besides, the ability of quercetin (a natural flavonoid) to prevent stress effects
      was evaluated. Quercetin was orally administered for 6 consecutive days before
      the pregnant rats were acutely exposed to predator stress on gestational day 19.
      Post-stress corticosterone level, brain oxidative stress parameters and anxiety
      like behavior were assessed in dams, whereas immune cell counts were postnatally
      determined in both male and female pups. Predator stress caused an oxidative
      stress in the brain and elicited an elevation in plasma corticosterone with
      concomitant behavioral impairment in dams. Prenatally-stressed pups mainly showed
      a decrease in total leukocytes and lymphocytes along with monocytosis and
      granulocytosis, but these changes were sex-dependent throughout the postnatal
      period studied. Quercetin pretreatment blocked the stress-induced corticosterone
      release and alleviated the brain oxidative stress with the maternal anxiety
      measures being slightly attenuated, whereas its effects on the offspring immune
      cell counts were mostly revealed at birth. Our findings suggest that late
      gestational exposure to traumatic events may cause anxiety symptoms in dams, in
      which corticosterone and brain oxidative stress play a certain role, and trigger
      negative immune changes in the early postnatal life of progeny. Notably,
      quercetin intake before such adverse events seems to be beneficial against
      negative outcomes in both dams and offspring.

PMID- 23541493
TI  - Chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 during
      puberty or adulthood reverses 3,4 methylenedioxymetamphetamine (MDMA)-induced
      deficits in recognition memory but not in effort-based decision making.
AB  - Cannabis and 3,4 methylenedioxymetamphetamine (MDMA, "ecstasy") are the most
      frequently combined illegal drugs among young adults in western societies. This
      study examined the effects of chronic co-administration of the cannabinoid
      receptor agonist WIN55,212-2 (WIN) and MDMA on working memory and effort-based
      decision making in rats. Treatment consisted of MDMA (7.5 mg/kg), WIN (1.2
      mg/kg), a combination of these substances (MDMA+WIN) or vehicle over a period of
      25 days during puberty (PD40-65) or adulthood (PD80-105). Ten days after the last
      treatment, WIN reversed MDMA-induced working memory deficits in the object
      recognition test in animals treated during adulthood or puberty, but had no
      influence on impairment of adult rats in the effort-based T-maze task. No
      differences were observed between groups of pubertally treated rats in the
      decision making task. During a subsequent acute drug challenge MDMA and MDMA+WIN
      decreased high reward choices in both age groups, indicating MDMA-induced cost
      aversive choice. Differential long-term interactions on the neuronal level in the
      hippocampus and MDMA-induced disturbances in cortico-limbic connections are
      suggested.

PMID- 23541494
TI  - The influence of smoking cigarettes on the high and desire for cocaine among
      active cocaine users.
AB  - The primary aim was to evaluate whether nicotine use alters the high or desire
      for cocaine among active cocaine users who concurrently smoke cigarettes.
      Participants answered the Fagerstrom Test for Nicotine Dependence (FTND),
      Nicotine-Stimulant Interaction Questionnaire (NSIQ), and Multiple Drug Use
      Questionnaire (MDUQ). These questionnaires employ subject recall of participants'
      drug use habits. The participants that smoked (N=163/188) were primarily African
      American males who were 45.0+/-0.5 (mean+/-S.E.M.) years of age, and used cocaine
      for 17.9+/-0.6 years and 19.8+/-0.6 days out of the last 30. These individuals
      smoked 14.0+/-0.8 cigarettes/day (CPD), scored 4.6+/-0.2 (on a scale of 0-10) on
      the FTND, and smoked cigarettes for 23.5+/-0.7 years. Two questions from the
      MDUQ, which evaluates the interaction between cocaine and nicotine, (-5: reduces
      effect, 0: no change, +5: increases effect) included "Does nicotine affect the
      high that you experience from cocaine?" and "Does nicotine affect your desire for
      cocaine?", and the scores were 1.3+/-0.2 and 0.8+/-0.2, respectively. The NSIQ
      also evaluated interactive effects of nicotine and cocaine, on a scale of 0 to
      100 (0: not at all, 100: most ever). Smokers responded most strongly that using
      cocaine increased both the urge to smoke and cigarette craving. Additional
      analyses were performed by separating participants into HighCPD vs. LowCPD groups
      via median split. The HighCPD group smoked 22.7+/-1.1 CPD while the LowCPD group
      smoked 6.4+/-0.3 CPD [F(1,161)=228.4, p<0.0001], and the HighCPD group had a mean
      FTND score twice that of the LowCPD group. Significant differences emerged
      between the two groups on multiple items of the NSIQ, but not the MDUQ. The
      subjective ratings of high and desire for cocaine, and several subjective effects
      produced by cocaine, were modestly altered by cigarette smoking. Taken together,
      these data suggest that cigarette smoking may augment the craving and high
      produced by cocaine.

PMID- 23541495
TI  - Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal
      nitric oxide synthase in the dorsal root ganglion and cuneate nucleus.
AB  - In this study, we investigated the role of nitric oxide (NO) in
      lysophosphatidylcholine (LPC) induced peripheral neuropathy by the use of nitric
      oxide synthase (NOS) inhibitors and NO donor. We found that LPC treatment of the
      median nerve induced neuropathic pain behaviors (allodynia and hyperalgesia) and
      nerve demyelination. Immunohistochemistry revealed that the amounts of neuronal
      NOS-like immunoreative (nNOS-LI) neurons in both the dorsal root ganglion (DRG)
      and cuneate nucleus (CN) increased and peaked at 1 week after LPC treatment.
      Following electrical stimulation of the LPC-treated nerve, the number of c-Fos-LI
      neurons in the ipsilateral CN also increased in a dose-dependent manner following
      LPC injection and peaked at 1 week. Administration of L-NAME (Nomega-Nitro-L
      arginine methyl ester) or 7-NI (7-nitroindazole) 1 week after 4% LPC injection
      attenuated tactile allodynia and thermal hyperalgesia. However, the application
      of the NO donor S-Nitroso-N-acetylpenicillamine (SNAP) only exacerbated thermal
      hyperalgesia. After electrical stimulation of the LPC-treated median nerve, the
      number of c-Fos-LI neurons in the CN diminished in the L-NAME and 7-NI groups,
      but increased in the SNAP group. Taken together, our findings suggest that
      advanced NO made by the dramatically increased number of nNOS in the DRG and CN
      might be involved in the neuropathic sensation and boosted neuronal activity in
      the CN after LPC treatment.

PMID- 23541496
TI  - Behavioral and serotonergic response changes in the Dhcr7-HET mouse model of
      Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a developmental disorder resulting from
      mutations to the Dhcr7 gene, which is required for cholesterol synthesis.
      Patients with SLOS typically exhibit a number of severe behavioral deficits and
      many are diagnosed with autistic spectrum disorder. Although the molecular
      pathophysiology underlying behavioral changes in SLOS and autism spectrum
      disorders is poorly understood, there is evidence for the involvement of the
      serotonergic system in SLOS and autism in general. Behavioral testing was
      undertaken to ascertain the basal behavioral differences between Dhcr7
      heterozygous (HET) and wild-type control mice and explore the utility of a Dhcr7
      HET mouse line in the development of new treatments for this disorder. Dhcr7-HET
      mice did not differ from wild-type control mice on basic measures of locomotor
      activity, anxiety and neuromuscular ability. However, female Dhcr7-HET mice at 6
      months of age or older were significantly more likely to win on the social
      dominance tube test against an unfamiliar mouse. Pharmacological testing, using
      the 5-HT2A agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), showed
      increased head-twitch response in Dhcr7-HET mice, which was apparent from 6
      months of age. No differences were found between the genotypes in testing for 5
      HT1A agonist 8-OH-DPAT-induced hypothermia. These data indicate an underlying
      dysfunction of the 5-HT2A receptors in Dhcr7-HET mice that warrants further
      investigation to establish how this may relate to behavioral disturbances in
      human patients carrying Dhcr7 mutations.

PMID- 23541497
TI  - Social competence vs responsiveness: similar but not same. A reply to Wolf and
      McNamara.

PMID- 23541498
TI  - Enhancement of the anaerobic hydrolysis and fermentation of municipal solid waste
      in leachbed reactors by varying flow direction during water addition and leachate
      recycle.
AB  - Poor performance of leachbed reactors (LBRs) is attributed to channelling,
      compaction from waste loading, unidirectional water addition and leachate flow
      causing reduced hydraulic conductivity and leachate flow blockage. Performance
      enhancement was evaluated in three LBRs M, D and U at 22 +/- 3 degrees C using
      three water addition and leachate recycle strategies; water addition was downflow
      in D throughout, intermittently upflow and downflow in M and U with 77% volume
      downflow in M, 54% volume downflow in U while the rest were upflow. Leachate
      recycle was downflow in D, alternately downflow and upflow in M and upflow in U.
      The strategy adopted in U led to more water addition (30.3%), leachate production
      (33%) and chemical oxygen demand (COD) solubilisation (33%; 1609 g against 1210
      g) compared to D (control). The total and volatile solids (TS and VS) reductions
      were similar but the highest COD yield (g-COD/g-TS and g-COD/g-VS removed) was in
      U (1.6 and 1.9); the values were 1.33 and 1.57 for M, and 1.18 and 1.41 for D
      respectively. The strategy adopted in U showed superior performance with more COD
      and leachate production compared to reactors M and D.

PMID- 23541499
TI  - Changes in middle cerebral artery velocity after carotid endarterectomy do not
      identify patients at high-risk of suffering intracranial haemorrhage or stroke
      due to hyperperfusion syndrome.
AB  - OBJECTIVES: To determine if significant increases in middle cerebral artery
      velocity (MCAV) or pulsatility index (PI) during and immediately after carotid
      endarterectomy (CEA) were predictive of patients suffering a stroke due to the
      hyperperfusion syndrome (HS) or intracerebral haemorrhage (ICH). METHODS:
      Transcranial Doppler (TCD) mean/peak MCAV and PI were recorded pre-operatively;
      pre-clamp; 1-min post-declamping; 10-min post-declamping and 30-min post
      operatively. The study was divided into two time periods; Group 1 (1995-2007);
      where there was no formal guidance for managing post-CEA hypertension (PEH) and
      Group 2 (2008-2012); where written guidelines for treating PEH were available.
      RESULTS: 11/1024 patients in Group 1 (1.1%) suffered a stroke due to HS/ICH,
      compared to 0/426 patients (0.0%) in Group 2 (p = 0.02). In Group 1; intra
      operative increases >100% in mean/peak MCAV and PI at 1 and 10-min post-clamp
      release had positive predictive values (PPV) of 1.2%, 6.3% and 20.0% and 2.9%,
      8.0% and 16.6% respectively. Post-operatively; a >100% increase in mean and peak
      MCAV had a PPV of 6.3% and 2.7% respectively. CONCLUSION: We were unable to
      demonstrate that significant increases in MCAV and PI were able to predict
      patients at increased risk of suffering a post-operative stroke due to HS or ICH.
      The provision of written guidance for managing PEH in Group 2 patients was
      associated with virtual abolition of ICH/HS.

PMID- 23541500
TI  - Quercetin solid lipid microparticles: a flavonoid for inhalation lung delivery.
AB  - PURPOSE: The aim of the present work was to develop solid lipid microparticles
      (SLMs), as dry powders containing quercetin for direct administration to the
      lung. METHODS: Quercetin microparticles were prepared by o/w emulsification via a
      phase inversion technique, using tristearin as the lipid component and
      phosphatidylcholine as an emulsifier. The quercetin SLMs were characterised for
      morphology, drug loading (15.5%+/-0.6, which corresponded to an encapsulation
      efficiency of 71.4%), particle size distribution, response to humidity,
      crystallinity, thermal behaviour and in vitro respirable fraction. Furthermore,
      the toxicity and the in vitro transport of the SLMs on an air liquid interface
      model of the Calu-3 cell line were also investigated using a modified twin-stage
      impinger apparatus. RESULTS: Results showed that quercetin SLMs could be
      formulated as dry powder suitable for inhalation drug delivery (20.5+/-3.3% fine
      particle fraction <=4.46MUm) that was absorbed, via a linear kinetic model across
      the Calu-3 monolayer (22.32+/-1.51% over 4h). In addition, quercetin SLMs were
      shown to be non-toxic at the concentrations investigated. Interestingly, no
      apical to basolateral transport of the micronised quercetin was observed over the
      period of study. CONCLUSIONS: These observations suggest quercetin diffusion was
      enhanced by the presence of the lipid/emulsifying excipients in the SLMs; however
      further studies are necessary to elucidate the exact mechanisms.

PMID- 23541501
TI  - Regulation of insulin biosynthesis in non-beta cells by a heat shock promoter.
AB  - Insulin production under the stringent control is the main issue in gene-based
      therapeutic strategies directed to type 1 diabetes. As a novel approach,
      inducible promoters may provide a promising tool for this purpose. In this study,
      we hypothesize that this control may be achieved via a promoter derived from the
      heat shock multigene family, Hsp70 A1A, which is inducible at 42 degrees C. To
      yield mature insulin in transfected fibroblasts (3T3/NIH), a recombinant human
      insulin gene consisting of sequences corresponding to furin cleavable sites was
      fused to the promoter. Heat-stimulated cells initiated to release biologically
      active insulin within 30 min with a ten-fold increase after 24 h. The role of
      upstream regulatory elements of the promoter on its activity in heat stress
      conditions was examined. No significant difference between the activity of the
      minimal and full-length promoters was observed. This promoter exhibited low basal
      expression in non-inducing conditions. Results indicate that this promoter is
      responsive to a heat induction after approximately 30 min which causes an
      efficient insulin production over a relatively short period of time. These
      potential features of this promoter may provide an insight to control the insulin
      production in vivo upon an external and physical stimulation.

PMID- 23541502
TI  - The good of two worlds: increasing complexity in cell-free systems.
AB  - In vitro biocatalytic systems have moved far beyond established uses in food,
      diagnostic, and chemical applications. As new strategies to construct and manage
      multiple enzymes in ever more complex systems are developed, novel applications
      emerge. In the field of chemistry, complex protein networks are applied to enable
      the production of fine chemicals, such as dihydroxyacetone phosphate, and even
      bulk chemicals, such as biofuels, from cheap sugars. Cell-free protein synthesis
      is applied to expanding protein and nucleic acid biochemistry and enabling novel
      assay formats, while programmable DNA-circuits can be exploited to engineer
      sensitive detection methods. Novel developments in chemical analytics such as
      real-time mass spectrometry to follow the metabolism online, directed physical
      assembly of network members facilitating substrate channeling, and encapsulation
      forming biofunctional subunits enable a better control and potential for
      optimization. 

PMID- 23541503
TI  - Microbial production of fatty acid-derived fuels and chemicals.
AB  - Fatty acid metabolism is an attractive route to produce liquid transportation
      fuels and commodity oleochemicals from renewable feedstocks. Recently, genes and
      enzymes, which comprise metabolic pathways for producing fatty acid-derived
      compounds (e.g. esters, alkanes, olefins, ketones, alcohols, polyesters) have
      been elucidated and used in engineered microbial hosts. The resulting strains
      often generate products at low percentages of maximum theoretical yields, leaving
      significant room for metabolic engineering. Economically viable processes will
      require strains to approach theoretical yields, particularly for replacement of
      petroleum-derived fuels. This review will describe recent progress toward this
      goal, highlighting the scientific discoveries of each pathway, ongoing
      biochemical studies to understand each enzyme, and metabolic engineering
      strategies that are being used to improve strain performance. 

PMID- 23541504
TI  - Frontiers of yeast metabolic engineering: diversifying beyond ethanol and
      Saccharomyces.
AB  - Microbial systems provide an attractive, renewable route to produce desired
      organic molecules such as fuels and chemicals. While attention within the field
      of metabolic engineering has mostly focused on Escherichia coli, yeast is a
      potent host and growing host for industrial products and has many outstanding,
      biotechnologically desirable native traits. Thus, there has been a recent shift
      in focus toward yeast as production hosts to replace E. coli. As such, products
      have diversified in yeast beyond simply ethanol. Additionally, nonconventional
      yeasts have been considered to move beyond Saccharomyces cerevisiae. This review
      highlights recent advances in metabolic engineering of yeasts for producing value
      added chemical compounds including alcohols, sugar derivatives, organic acids,
      fats, terpenes, aromatics, and polyketides. Furthermore, we will also discuss the
      future direction of metabolic engineering of yeasts. 

PMID- 23541505
TI  - Advances in metabolic pathway and strain engineering paving the way for
      sustainable production of chemical building blocks.
AB  - Bio-based production of chemical building blocks from renewable resources is an
      attractive alternative to petroleum-based platform chemicals. Metabolic pathway
      and strain engineering is the key element in constructing robust microbial
      chemical factories within the constraints of cost effective production. Here we
      discuss how the development of computational algorithms, novel modules and
      methods, omics-based techniques combined with modeling refinement are enabling
      reduction in development time and thus advance the field of industrial
      biotechnology. We further discuss how recent technological developments
      contribute to the development of novel cell factories for the production of the
      building block chemicals: adipic acid, succinic acid and 3-hydroxypropionic acid.

PMID- 23541506
TI  - Effect of different arginine methylations on the thermodynamics of Tat peptide
      binding to HIV-1 TAR RNA.
AB  - RNA-binding proteins are an important class of mediators that regulate cell
      function and differentiation. Methylation of arginine, a post-translational
      modification (PTM) found in these proteins, can modulate their function. Arginine
      can be monomethylated or dimethylated, depending on the type of methyl
      transferases involved. This paper describes a comparative study of the
      thermodynamics of unmodified and modified Tat peptide interaction with TAR RNA,
      where the peptide is methylated at epsilon (E) and eta (eta) nitrogen atoms of
      guanidinium group of arginine side chain at position 52 or 53. The results
      indicate that monomethylation of arginine at epsilon (E) nitrogen atom enhances
      binding affinity, owing to a more favourable enthalpy component which overrides
      the less favourable entropy change. In contrast, monomethylation of arginine
      residue at eta nitrogen results in reduced binding affinity originating
      exclusively from a less favourable enthalpy change leaving entropic component
      unaffected. However, in case of simultaneous methylation at E and eta positions,
      the binding parameters remain almost unaffected, when compared to the unmodified
      peptide. In case of symmetric dimethylation at eta position the observed enthalpy
      change of the binding was found to be smaller than the values obtained for the
      unmodified peptide. Asymmetric dimethylation at eta position showed the most
      reduced binding affinities owing to less favourable enthalpy changes. These
      results provide insights that enable elucidation of the biological outcome of
      arginine methylation as PTMs that regulate protein function, and will contribute
      to our understanding of how these PTMs are established in vitro and in vivo.

PMID- 23541507
TI  - Firing patterns of muscle sympathetic neurons during short-term use of continuous
      positive airway pressure in healthy subjects and in chronic heart failure
      patients.
AB  - The current study tested the hypothesis that modification in central hemodynamics
      during short-term continuous positive airway pressure (CPAP) application was
      accompanied by altered firing patterns of sympathetic nerve activity in CHF
      patients and healthy subjects. Muscle sympathetic nerve activity (MSNA),
      hemodynamic and ventilatory parameters were obtained from 8 healthy middle aged
      subjects and 7 CHF patients. Action potentials (APs) were extracted from MSNA
      neurograms, quantified as AP frequency and classified into different sized
      clusters. While on CPAP at 10cm H2O, multi-unit MSNA, AP frequency and mean burst
      area/min increased in healthy middle aged subjects (p<0.05) whereas CPAP had no
      effect on these variables in CHF patients. In conclusion, the impact of CPAP on
      central hemodynamics in healthy individuals elicited a moderate activation of
      sympathetic neurons through increased AP firing frequency, whereas in CHF
      patients both hemodynamics and MSNA remained unaltered.

PMID- 23541509
TI  - A drug education tool developed for older adults changes knowledge, beliefs and
      risk perceptions about inappropriate benzodiazepine prescriptions in the elderly.
AB  - OBJECTIVE: To develop and test an educational tool for older adults that
      increases risk perception about benzodiazepines through knowledge acquisition and
      change in beliefs. METHODS: A written educational tool was mailed to 144
      benzodiazepine consumers aged >=65 years recruited from community pharmacies.
      Knowledge and beliefs about inappropriate prescriptions were queried prior to and
      1-week after the intervention. Primary outcome was a change in risk perception.
      Explanatory variables were a change in knowledge and beliefs about medications.
      Self-efficacy for tapering and intent to discuss discontinuation were also
      measured. RESULTS: Post-intervention, 65 (45.1%) participants perceived increased
      risk. Increased risk perceptions were explained by better knowledge acquisition
      (mean change score 0.9, 95% CI (0.5, 1.3)), and a change in beliefs (BMQ
      differential mean change score -5.03, 95% CI (-6.4, -3.6)), suggesting
      elicitation of cognitive dissonance. Self-efficacy for tapering, (mean change
      score 31.2, 95% CI (17.9, 44.6)), and intent to discuss discontinuation of
      benzodiazepine with a doctor (83.1% vs 44.3%, p<0.001) were higher among
      participants who perceived increased risk. CONCLUSION: Risk perception
      surrounding inappropriate prescriptions can be altered through direct delivery of
      an educational tool to aging consumers. PRACTICE IMPLICATIONS: Patients should be
      targeted directly with information to catalyze discontinuation of inappropriate
      prescriptions.

PMID- 23541508
TI  - Nonoperative management of odontoid fractures: a review of 59 cases.
AB  - OBJECTIVES: Surgical treatment of odontoid fractures is recommended by many
      surgeons to prevent sudden neurologic injury or progressive myelopathy. Less
      aggressive approach to the treatment of odontoid fractures has been advocated by
      some authors especially in the elderly population. Very few reports have followed
      up patients' outcomes following conservative treatment of odontoid fractures.
      Here we evaluate the clinical and radiographic results of patients without
      myelopathy treated without surgery for an odontoid type fracture. PATIENTS AND
      METHODS: 101 patients with traumatic odontoid fracture admitted to the
      Pennsylvania State Hershey Medical Center between 1998 and 2008. Fractures were
      defined using a CT scan according to the Anderson-D'Alonzo Classification.
      Conservative treatment was pursued in appropriately selected patients. RESULTS:
      Fifty-nine patients were selected to be treated in a cervical collar. Sixteen
      patients failed using radiographic evidence and continued neck pain. Fourteen
      patients went on to be surgically stabilized. The other two patients opted to
      continue with cervical orthosis and regular clinical evaluations. The Forty-three
      remaining patients had stable imaging studies and with no other complaints. None
      of the patients developed myelopathy symptoms during the follow-up period.
      CONCLUSIONS: Our results indicate that a select group of patients with odontoid
      fracture who are deemed stable on initial evaluation in a cervical orthosis may
      be effectively managed non-operatively. None of the patients who were managed
      conservatively had clinical worsening during the period of management. The
      decision to proceed with surgical treatment was based on failure of resolution of
      neck pain or worsening or concerning instability on imaging studies. However in
      many patients, even elderly patients in a surgical risks are greater, many
      odontoid fractures can be safely managed in a cervical orthosis.

PMID- 23541510
TI  - Should culture affect practice? A comparison of prognostic discussions in
      consultations with immigrant versus native-born cancer patients.
AB  - OBJECTIVE: Poor prognosis is difficult to impart, particularly across a cultural
      divide. This study compared prognostic communication with immigrants (with and
      without interpreters) versus native-born patients in audio-taped oncology
      consultations. METHODS: Ten oncologists, 78 patients (31 Australian-born, 47
      immigrants) and 115 family members participated. The first two consultations
      after diagnosis of incurable disease were audiotaped, transcribed and coded. 142
      consultations were included in the analysis. RESULTS: Fifty percent of doctor and
      59% of patient prognostic speech units were not interpreted or interpreted non
      equivalently when an interpreter was present. Immigrant status predicted few
      prognostic facts, and oncologist characteristics no prognostic facts, disclosed.
      Oncologists were significantly less likely to convey hope to immigrants
      (p=0.0004), and more likely to use medical jargon (p=0.009) than with Australian
      born patients. Incurable disease status and a limited life span were commonly
      acknowledged, generally with no timeframe provided. Physical issues were
      discussed more commonly than emotional aspects. CONCLUSIONS: While culture did
      not appear to influence doctor speech, interpreters filtered or blocked much
      prognostic communication. PRACTICE IMPLICATIONS: Initiatives to empower all
      patients to attain needed information, optimise communication when an interpreter
      is present and train cancer health professionals in culturally appropriate care,
      are urgently required.

PMID- 23541511
TI  - Three ERF transcription factors from Chinese wild grapevine Vitis
      pseudoreticulata participate in different biotic and abiotic stress-responsive
      pathways.
AB  - Ethylene response factor (ERF) functions as an important plant-specific
      transcription factor in regulating biotic and abiotic stress response through
      interaction with various stress pathways. We previously obtained three ERF
      members, VpERF1, VpERF2, and VpERF3 from a highly powdery mildew (PM)-resistant
      Chinese wild Vitis pseudoreticulata cDNA full-length library. To explore their
      functions associated with plant disease resistance or biotic stress, we report
      here to characterize three ERF members from this library. PM-inoculation analysis
      on three different resistant grapevine genotypes revealed that three VpERFs
      displayed significant responses, but a different expression pattern. Over
      expression of VpERF1, VpERF2, and VpERF3 in transgenic tobacco plants
      demonstrated that VpERF2 and VpERF3 enhanced resistance to both bacterial
      pathogen Ralstonia solanacearum and fungal pathogen Phytophtora parasitica var.
      nicotianae Tucker. Importantly, VpERF1-overexpressing transgenic Arabidopsis
      plants increased susceptibility toward these pathogens. Investigation on drought,
      cold, and heat treatments suggested, VpERF2 was distinctly induced, whereas
      VpERF3 displayed a very weak response and VpERF1 was distinctly induced by
      drought and heat. Concurrently, VpERF3 was significantly induced by salicylic
      acid (SA), methyl jasmonate (MeJA), and ET. Our results showed that the three
      VpERFs from Chinese wild V. pseudoreticulata play different roles in either
      preventing disease progression via regulating the expression of relevant defense
      genes, or directly involving abiotic stress responsive pathways.

PMID- 23541512
TI  - A mechanism for localized lignin deposition in the endodermis.
AB  - The precise localization of extracellular matrix and cell wall components is of
      critical importance for multicellular organisms. Lignin is a major cell wall
      modification that often forms intricate subcellular patterns that are central to
      cellular function. Yet the mechanisms of lignin polymerization and the
      subcellular precision of its formation remain enigmatic. Here, we show that the
      Casparian strip, a lignin-based, paracellular diffusion barrier in plants, forms
      as a precise, median ring by the concerted action of a specific, localized NADPH
      oxidase, brought into proximity of localized peroxidases through the action of
      Casparian strip domain proteins (CASPs). Our findings in Arabidopsis provide a
      simple mechanistic model of how plant cells regulate lignin formation with
      subcellular precision. We speculate that scaffolding of NADPH oxidases to the
      downstream targets of the reactive oxygen species (ROS) that they produce might
      be a widespread mechanism to ensure specificity and subcellular precision of ROS
      action within the extracellular matrix.

PMID- 23541513
TI  - Nature adventure rehabilitation for combat-related posttraumatic chronic stress
      disorder: a randomized control trial.
AB  - Chronic combat-related posttraumatic stress disorder (CR-PTSD) is a condition
      with many treatment barriers. Nature Adventure Rehabilitation (NAR) as a second
      line or as a supplemental intervention has the potential to overcome some of
      these barriers and incorporate aspects of successful treatment modalities for
      PTSD within an experiential learning paradigm. In a pre-post controlled trial, CR
      PTSD veterans (n=22) underwent a 1-year NAR intervention compared to a waiting
      list (WL) control group (n=20). Posttraumatic symptoms (PTS), depression,
      functional problems, quality of life, perceived control over illness (PCI) and
      hope were measured by self report measures. PTS, emotional and social quality of
      life, PCI, hope and functioning improved significantly. Change in PTS was
      contingent upon change in PCI. The current study is the first to present NAR as a
      promising supplemental intervention for chronic CR-PTSD. NAR seems to work
      through a process of behavioral activation, desensitization, gradual exposure to
      anxiety evoking situations and gaining control over symptomatology. 

PMID- 23541514
TI  - Development of PVP/PEG mixtures as appropriate carriers for the preparation of
      drug solid dispersions by melt mixing technique and optimization of dissolution
      using artificial neural networks.
AB  - The effect of plasticizer's (PEG) molecular weight (MW) on PVP based solid
      dispersions (SDs), prepared by melt mixing, was evaluated in the present study
      using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600,
      and 2000 g/mol were tested, and the effect of drug content, time and temperature
      of melt mixing on the physical state of Tibolone, and the dissolution
      characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were
      completely miscible, while blends were heterogeneous. Furthermore, a single Tg
      recorded in all samples, indicating that Tibolone was dispersed in a molecular
      lever (or in the form of nanodispersions), varied with varying PEG's molecular
      weight, melt mixing temperature, and drug content, while FTIR analysis indicated
      significant interactions between Tibolone and PVP/PEG matrices. All prepared
      solid dispersion showed long-term physical stability (18 months in room
      temperature). The extent of interaction between mixture components was verified
      using Fox and Gordon-Taylor equations. Artificial neural networks, used to
      correlate the studied factors with selected dissolution characteristics, showed
      good prediction ability.

PMID- 23541515
TI  - The influence of the BCL11A polymorphism on the phenotype of patients with beta
      thalassemia could be affected by the beta globin locus control region and/or the
      Xmn1-HBG2 genotypic background.
AB  - To study the influence of the beta globin locus control region (LCR) genotypic
      background on the phenotype modifying role of BCL11A polymorphisms, 100 cases of
      thalassemia, 48 homozygous for the A allele and 52 homozygous for the G allele at
      the 5'HS4-LCR palindromic polymorphic site were genotyped for two BCL11A single
      nucleotide polymorphisms (rs11886868 and rs766432) in the intronic region of this
      gene. The effect of these polymorphisms on HbF variation was also examined in 122
      normal individuals. The 5'HS4-LCR had the most significant role in determining
      the phenotype of these thalassemia patients. BCL11A polymorphisms showed a
      significant role in determining the phenotype of patients homozygous for the G
      allele at 5'HS4-LCR. However, the majority of patients homozygous for the A
      allele at 5'HS4-LCR, showed a severe phenotype, regardless of the BCL11A
      genotype. These results, without undermining the strength of BCL11A as a silencer
      of the gamma globin gene, suggest that the LCR background, by governing the state
      of BCL11A binding to this region, plays a more significant role in determining
      the thalassemia phenotype than the level of BCL11A protein expression, that might
      be influenced by single nucleotide polymorphisms in intronic regions of the
      BCL11A gene. Functional studies to confirm the interactions between BCL11A and
      LCR could be useful in designing pharmacogenetic strategies for the treatment of
      beta thalassemia major.

PMID- 23541516
TI  - Characteristics of French people using organised colorectal cancer screening.
      Analysis of the 2010 French Health, Healthcare and Insurance Survey.
AB  - OBJECTIVE: To analyse relationships between socio-demographic characteristics,
      healthcare access, and behaviour with regard to participation in organised
      colorectal cancer (CRC) screening. METHODS: We analysed a subset of 2,276
      individuals from a cross-sectional population-based survey of French households
      in 2010. The outcome was participation in CRC screening using multiple logistic
      regression. The studied variables included socio-demographic characteristics,
      healthcare access-related variables, and health or perceived health. RESULTS:
      Age, living in a pilot district for CRC screening, and having a private
      additional insurance were associated with participation in CRC screening for both
      genders. In men, other characteristics were associated: not having 100% coverage
      for medical fees for a long-term disease, having consulted a medical specialist
      in the last 12 months, and not smoking. In women, other cancer screening
      behaviours were associated with participation in CRC screening. Results also
      showed that 81.4% of individuals, who did not have a Hemoccult(r) test, consulted
      a GP in the last 12 months. CONCLUSIONS: Despite efforts made, results confirmed
      that CRC screening differed among socioeconomic groups. GPs should be encouraged
      to systematically recommend CRC screening to their patients fitting the criteria
      of the organised CRC screening programme and further investigation is required to
      optimise information strategies targeting GPs.

PMID- 23541517
TI  - Improvement in iodine status of pregnant Australian women 3 years after
      introduction of a mandatory iodine fortification programme.
AB  - INTRODUCTION: In order to address population-level mild iodine deficiency in
      Australia, a mandatory iodine fortification programme of salt used in bread was
      introduced in late 2009. METHODS: A before-after study was conducted to assess
      changes in median urinary iodine concentration (MUIC) measurements, according to
      supplement use, in convenience samples of pregnant women attending a public
      antenatal clinic in a regional area of New South Wales, Australia in 2008
      (n=139), 2011 (n=147) and 2012 (n=114). Knowledge and practices related to iodine
      nutrition were investigated in 2012, using self-administered questionnaires.
      RESULTS: The mild iodine deficiency confirmed pre-fortification (MUIC (IQR)=87.5
      (62-123.5; n=110)) has steadily improved to 145.5 MUg/L (91-252) in 2011 (n=106)
      and 166 (97-237) in 2012 (n=95) (sufficiency >= 150 MUg/L). However, only women
      taking supplements containing iodine had MUIC indicative of sufficiency in both
      years surveyed post fortification (2011: 178 MUg/L vs. 109 MUg/L, P<0.001; 2012:
      202 MUg/L vs. 124 MUg/L, P<0.05). Despite bread being the vehicle for iodine
      fortification, dairy foods remained major contributors to total iodine intake
      (58%). Overall knowledge regarding health implications of iodine deficiency was
      poor. CONCLUSIONS: Iodine status of women has improved since the introduction of
      mandatory iodine fortification; however supplementation is indicated during
      pregnancy.

PMID- 23541518
TI  - Identification of a Bacillus thuringiensis Cry8Da toxin-binding glucosidase from
      the adult Japanese beetle, Popillia japonica.
AB  - Cry8Da from Bacillus thuringiensis galleriae SDS-502 has insecticidal activity
      against both the larvae and adult Japanese beetle (Popillia japonica Newman). The
      receptor determines the specificity of the insecticidal activity of Cry proteins
      and hence, in order to reveal the mode of action of Cry toxin, receptor
      identification is a necessary step. However, a receptor for Cry8-type toxin has
      not been identified in the Scarabaeidae family of insects. Therefore, we aimed to
      identify the receptor of Cry8Da toxin in adult P. japonica BBMV. A ligand blot
      showed the Cry8Da toxin only bound to a 150kDa protein in the BBMV of adult P.
      japonica. In order to identify the Cry8Da toxin binding protein, it was purified
      by column chromatography and three internal amino acid sequences were determined.
      Two of the three internal amino acid sequences shared homology with Coleopteran
      beta-glucosidases. In addition, the fraction containing the Cry8Da toxin binding
      protein had beta-glucosidase activity but no aminopeptidase N and alkaline
      phosphatase activity, both of which are commonly reported as receptors for Cry
      toxins in Lepidopteran and Dipteran insects. The beta-glucosidase homologous
      genes could be amplified by PCR using degenerate oligonucleotide primers designed
      from a conserved sequence of Coleopteran beta-glucosidases and an internal amino
      acid sequence of the Cry8Da toxin binding protein. Taken together, the beta
      glucosidase in adult P. japonica BBMV is the receptor for B. thuringiensis Cry8Da
      toxin.

PMID- 23541519
TI  - V(H)H (nanobody) directed against human glycophorin A: a tool for autologous red
      cell agglutination assays.
AB  - The preparation of a V(H)H (nanobody) named IH4 that recognizes human glycophorin
      A (GPA) is described. IH4 was isolated by screening a library prepared from the
      lymphocytes of a dromedary immunized by human blood transfusion. Phage display
      and panning against GPA as the immobilized antigen allowed isolating this V(H)H.
      IH4, representing 67% of the retrieved V(H)H sequences, was expressed as a
      soluble correctly folded protein in SHuffle Escherichia coli cells, routinely
      yielding approximately 100 mg/L fermentation medium. Because IH4 recognizes GPA
      independently of the blood group antigens, it recognizes red cells of all humans
      with the possible exception of those with some extremely rare genetic background.
      The targeted linear epitope comprises the GPA Y52PPE55 sequence. Based on surface
      plasmon resonance results, the dissociation constant of the IH4-GPA equilibrium
      is 33 nM. IH4 is a stable protein with a transition melting temperature of 75.8 
      degrees C (measured by differential scanning calorimetry). As proof of concept,
      we fused HIV p24 to IH4 and used the purified construct expressed in E. coli to
      show that IH4 was amenable to the preparation of autologous erythrocyte
      agglutination reagents: reconstituted blood prepared with serum from an HIV
      positive patient was readily agglutinated by the addition of the bifunctional
      reagent.

PMID- 23541520
TI  - Development of a highly sensitive three-dimensional gel electrophoresis method
      for characterization of monoclonal protein heterogeneity.
AB  - Three-dimensional gel electrophoresis (3-DE), which combines agarose gel
      electrophoresis and isoelectric focusing/SDS-PAGE, was developed to characterize
      monoclonal proteins (M-proteins). However, the original 3-DE method has not been
      optimized and its specificity has not been demonstrated. The main goal of this
      study was to optimize the 3-DE procedure and then compare it with 2-DE. We
      developed a highly sensitive 3-DE method in which M-proteins are extracted from a
      first-dimension agarose gel, by diffusing into 150 mM NaCl, and the recovery of M
      proteins was 90.6%. To validate the utility of the highly sensitive 3-DE, we
      compared it with the original 3-DE method. We found that highly sensitive 3-DE
      provided for greater M-protein recovery and was more effective in terms of
      detecting spots on SDS-PAGE gels than the original 3-DE. Moreover, highly
      sensitive 3-DE separates residual normal IgG from M-proteins, which could not be
      done by 2-DE. Applying the highly sensitive 3-DE to clinical samples, we found
      that the characteristics of M-proteins vary tremendously between individuals. We
      believe that our highly sensitive 3-DE method described here will prove useful in
      further studies of the heterogeneity of M-proteins.

PMID- 23541521
TI  - Separation of actin-dependent and actin-independent lipid rafts.
AB  - Lipid rafts have been isolated on the basis of their resistance to various
      detergents and more recently by using detergent-free procedures. The actin
      cytoskeleton is now recognized as a dynamic regulator of lipid raft stability. We
      carefully analyzed the effects of the cortical actin-disrupting agent latrunculin
      B on lipid raft markers of both protein and lipid nature and show that two
      detergent-free membrane subtypes can be isolated and separated from each other on
      a one-step density gradient combined with pooling of the appropriate gradient
      fractions. These two subtypes differ in their dependence on the cortical actin
      cytoskeleton.

PMID- 23541522
TI  - Differential pulse voltammetric determination of metformin using copper-loaded
      activated charcoal modified electrode.
AB  - A simple and sensitive carbon paste electrode has been developed for the
      electrochemical trace determination of metformin (MET). This sensor was designed
      by Copper(II)-loaded activated charcoal (Cu-AC) in the carbon paste electrode
      (CPE), which provides remarkably improved sensitivity and selectivity for the
      electrochemical stripping assay of MET. The drug was accumulated on the surface
      of the electrode through formation of a coordination complex with copper ions,
      which enhanced the sensitivity of the method. The effects of various copper(II)
      salts and oxidation states of copper (within the carbon paste electrode) on MET
      oxidation behavior were also investigated. The calibration graph was linear over
      the concentration range of 50 nM to 60 MUM MET, and the detection limit was
      calculated as 9 nM. The proposed electrode was used successfully for MET
      determination in real matrices.

PMID- 23541523
TI  - Application of Laguerre based adaptive predictive control to Shape Memory Alloy
      (SMA) Actuator.
AB  - This paper discusses the use of an existing adaptive predictive controller to
      control some Shape Memory Alloy (SMA) linear actuators. The model consists in a
      truncated linear combination of Laguerre filters identified online. The
      controller stability is studied in details. It is proven that the tracking error
      is asymptotically stable under some conditions on the modelling error. Moreover,
      the tracking error converge toward zero for step references, even if the
      identified model is inaccurate. Experimental results obtained on two different
      kind of actuator validate the proposed control. They also show that it is robust
      with regard to input constraints.

PMID- 23541524
TI  - Dosimetric comparison of photon and proton treatment techniques for
      chondrosarcoma of thoracic spine.
AB  - Chondrosarcomas are relatively radiotherapy resistant, and also delivering high
      radiation doses is not feasible owing to anatomic constraints. In this study, the
      feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic
      spine is explored and compared with other available photon and proton
      radiotherapy techniques in the clinical setting. A patient was treated for high
      grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively,
      the tomotherapy plan was compared with intensity-modulated radiation therapy,
      dynamic arc photon therapy, and proton therapy. Two primary comparisons were
      made: (1) comparison of normal tissue sparing with comparable target volume
      coverage (plan-1), and (2) comparison of target volume coverage with a
      constrained maximum dose to the cord center (plan-2). With constrained target
      volume coverage, proton plans were found to yield lower mean doses for all organs
      at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning
      resulted in the lowest mean dose to all organs at risk amongst photon-based
      methods. For cord dose constrained plans, the static-field intensity-modulated
      radiation therapy and dynamic arc plans resulted target underdosing in 20% and
      12% of planning target volume2 volumes, respectively, whereas both proton and
      tomotherapy plans provided clinically acceptable target volume coverage with no
      portion of planning target volume2 receiving less than 90% of the prescribed
      dose. Tomotherapy plans are comparable to proton plans and produce superior
      results compared with other photon modalities. This feasibility study suggests
      that tomotherapy is an attractive alternative to proton radiotherapy for
      delivering high doses to lesions in the thoracic spine. 

PMID- 23541525
TI  - Genetic and epigenetic determinants of DNA replication origins, position and
      activation.
AB  - In the genome of eukaryotic cells, DNA synthesis is initiated at multiple sites
      called origins of DNA replication. Origins must fire only once per cell cycle and
      how this is achieved is now well understood. However, little is known about the
      mechanisms that determine when and where replication initiates in a given cell. A
      large body of evidence indicates that origins are not equal in terms of
      efficiency and timing of activation. Origin usage also changes concomitantly with
      the different cell differentiation programs. As DNA replication occurs in the
      context of chromatin, initiation could be influenced by multiple parameters, such
      as nucleosome positioning, histone modifications, and three-dimensional (3D)
      organization of the nucleus. This view is supported by recent genome-wide studies
      showing that DNA replication profiles are shaped by genetic and epigenetic
      processes that act both at the local and global levels to regulate origin
      function in eukaryotic cells.

PMID- 23541526
TI  - Neurotoxicity of the anticoagulant-selective E149A-activated protein C variant
      after focal ischemic stroke in mice.
AB  - Wild type (WT) activated protein C (APC) and cytoprotective-selective APC
      variants such as 3K3A-APC (<10% anticoagulant but normal cytoprotective activity)
      are neuroprotective in murine focal ischemic stroke models. Here we compared the
      neuroprotective effects of the anticoagulant-selective E149A-APC variant (>3-fold
      increased anticoagulant activity but defective cytoprotective activities) to
      those of the cytoprotective-selective 5A-APC variant (<10% anticoagulant
      activity). After transient distal middle cerebral artery occlusion, mice received
      a vehicle, E149A-APC or 5A-APC at 0.2mg/kg at 4h after stroke. Treatment with 5A
      APC was neuroprotective, as it improved performance on forelimb use asymmetry
      test and foot fault test (P<0.05), reduced by 48% and 50% the infarct and edema
      volumes, respectively (P<0.05), and was not associated with an increased risk of
      bleeding as indicated by normal hemoglobin levels in the ischemic brain at day 7.
      In contrast, E149A-APC treatment worsened neurological outcome determined by foot
      fault tests and forelimb use asymmetry tests, and increased significantly by 44%
      and 60% infarct and edema volume, respectively (P<0.05). At 7days after
      treatment, E149A-APC compared to vehicle or 5A-APC notably increased by ~5-fold
      the hemoglobin level in the ischemic hemisphere suggesting it provoked
      significant intracerebral bleeding. Thus, the enhanced anticoagulant activity of
      E149A-APC increased post-ischemic accumulation of neurotoxic erythrocyte-derived
      hemoglobin which likely worsened the neurological and neuropathological outcomes
      after stroke. Our data emphasize that APC's cytoprotective activities, but not
      its anticoagulant activity, are key for APC neuroprotection after transient
      ischemic stroke.

PMID- 23541527
TI  - Feasibility of the video-laryngoscope (GlideScope(r)) for endotracheal intubation
      during uninterrupted chest compressions in actual advanced life support: a
      clinical observational study in an urban emergency department.
AB  - AIM: This is the first clinical trial to evaluate whether successful endotracheal
      intubation (ETI) using a video-laryngoscope (VL) (GlideScope((r))) can be
      performed easily without chest compression interruptions during actual
      cardiopulmonary resuscitation (CPR) after brief VL training, regardless of the
      physicians' levels of experience with successful ETI in the past. METHODS: We
      performed a prospective, clinical observation study. After completing a brief 1-h
      VL training, 14 emergency physicians intubated arrest victims using a VL during
      CPR in the emergency department for a period of 1 year. All CPRs were recorded by
      video and were reviewed retrospectively. Outcomes were based on the success rate
      of the first ETI attempt, the time until the first successful ETI attempt (TUS)
      and chest compression interruptions during ETI. The outcomes were compared based
      on the physicians' varying experience with successful ETI in the past. RESULTS:
      Of 71 CPRs, all cases were successful and 66 cases (93%) were successful at the
      first ETI attempt with no significant chest compression interruptions. The median
      TUS was 41.5 (33.8, 61.2) s. There were no differences between less and more
      experienced physicians in the success rate of the first ETI attempts (97.3% vs.
      88.2%; p=0.187), or the median TUS (41.5 (33.5, 58.0) vs. 42.0 (33.8, 64.3) s;
      p=0.842). CONCLUSIONS: In a clinical setting, the use of a VL had a high success
      rate for the first ETI attempt with notably few chest compression interruptions,
      regardless of the physicians' varying experience with successful ETI in the past.

PMID- 23541528
TI  - Evidence-based recommendations on automated external defibrillator training for
      children and young people in Flanders-Belgium.
AB  - OBJECTIVE: The aim of the study was to identify the most relevant literature on
      skills, attitude and behaviour of children and young people towards the use of an
      automated external defibrillator (AED) and then develop recommendations according
      to the principles of evidence-based practice. These recommendations were to serve
      as a basis for educational materials which would ensure that the implementation
      of AED-training within schools and youth organisations would be a simple process.
      METHODS: A systematic literature search was performed using a specific research
      question: "Are children of different ages able/willing to use an AED after a
      training compared to another/no training?". A guideline development panel meeting
      was organised to formulate practice guidelines. The panel consisted of experts
      from different fields (medicine, education and psychology) and representatives of
      the end users (teachers and youth leaders). RESULTS: The systematic literature
      search identified five studies concerning AED skills by children and young
      people, and two studies concerning the attitudes and behaviour of children and
      young people towards the use of an AED. The guideline development panel carefully
      examined the available scientific evidence, took into consideration the skills
      and attitudes of children and young people, including the psychological
      consequences of managing a potentially life-saving situation and formulated
      evidence-based recommendations and good practice points. CONCLUSION: Based on
      these recommendations, an education programme and new educational materials have
      been developed by the Belgian Red Cross-Flanders. In this way school staff and
      youth leaders are properly supported to teach first aid techniques to children
      and young people (6-18 years).

PMID- 23541529
TI  - Bacterial and archaeal globins - a revised perspective.
AB  - A bioinformatics survey of putative globins in over 2200 bacterial and some 140
      archaeal genomes revealed that over half the bacterial and approximately one
      fifth of archaeal genomes contain genes encoding globins that were classified
      into three families: the M (myoglobin-like), and S (sensor) families all
      exhibiting the canonical 3/3 myoglobin fold, and the T family (truncated
      myoglobin fold). Although the M family comprises 2 subfamilies, flavohemoglobins
      (FHbs) and single domain globins (SDgbs), the S family encompasses chimeric
      globin-coupled sensors (GCSs), single domain Pgbs (protoglobins) and SSDgbs
      (sensor single domain globins). The T family comprises three classes TrHb1s,
      TrHb2s and TrHb3s, characterized by the abbreviated 2/2 myoglobin fold. The
      Archaea contain only Pgbs, GCSs and TrHb1s. The smallest globin-bearing genomes
      are the streamlined genomes (~1.3Mbp) of the SAR11 clade of alphaproteobacteria
      and the slightly larger (ca. 1.7Mbp) genomes of Aquificae. The smallest genome
      with members of all three families is the 2.3Mbp genome of the extremophile
      Methylacidiphilum infernorum (Verrumicrobia). Of the 147 possible combinations of
      the eight globin subfamilies, only 83 are observed. Although binary combinations
      are infrequent and ternary combinations are rare, the FHb+TrHb2 combination is
      the most commonly observed. Of the possible functions of bacterial globins we
      discuss the two principal ones - nitric oxide detoxification via the NO
      dioxygenase or denitrosylase activities and the sensing of oxygen concentration
      in the environmental niche. In only few cases has a physiological role been
      demonstrated in vivo. This article is part of a Special Issue entitled: Oxygen
      Binding and Sensing Proteins. 

PMID- 23541530
TI  - The unusual mechanism of inhibition of the p90 ribosomal S6 kinase (RSK) by
      flavonol rhamnosides.
AB  - All known protein kinases share a bilobal kinase domain with well conserved
      structural elements. Because of significant structural similarities of nucleotide
      binding pocket, the development of highly selective kinase inhibitors is a very
      challenging task. Flavonols, naturally occurring plant metabolites, have long
      been known to inhibit kinases by mimicking the adenine moiety. Interestingly,
      recent data show that some flavonol glycosides are more selective, although
      underlying mechanisms were unknown. Crystallographic data from our laboratory
      revealed that the N-terminal kinase domain of p90 ribosomal S6 kinase, isoform 2,
      binds three different flavonol rhamnosides in a highly unusual manner, distinct
      from other kinase inhibitor interactions. The kinase domain undergoes a
      reorganization of several structural elements in response to the binding of the
      inhibitors. Specifically, the main beta-sheet of the N-lobe undergoes a twisting
      rotation by ~56 degrees  around an axis passing through the N- and C-lobes,
      leading to the restructuring of the canonical ATP-binding pocket into pockets
      sterically adapted to the inhibitor shape. The flavonol rhamnosides appear to
      adopt compact, but strained conformations with the rhamnose moiety swept under
      the B-ring of flavonol, unlike the structure of the free counterparts in
      solution. These data suggest that the flavonol glycoside scaffold could be used
      as a template for new inhibitors selective for the RSK family. This article is
      part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).

PMID- 23541531
TI  - Intersection of selenoproteins and kinase signalling.
AB  - The small, obscure group of selenoprotein oxidoreductases and the huge clan of
      kinases, the workhorses of cellular signalling, are rarely discussed together.
      Focusing on selenoproteins of unknown structures, we predict a thioredoxin-like
      fold for the Selenoprotein N (SelN) family and use the structure to rationalise
      effects of the muscular myopathy-linked mutations in the gene coding SelN.
      Discussing the recent prediction of a protein kinase-like domain in the
      Selenoprotein O (SelO), we reiterate evidence for an oxidoreductase function
      alongside the predicted kinase domain. Thus, we propose that SelO, the strongly
      conserved kinase-cum-tentative-oxidoreductase may reflect oxidoreductase
      regulation of kinase networks. Also, we use bibliometric and systems biology
      approach to explore the kinase-selenoprotein relationships that begin to emerge
      from the literature. This article is part of a Special Issue entitled: Inhibitors
      of Protein Kinases (2012).

PMID- 23541533
TI  - [A case report of syphilitic uveitis and deafness].
AB  - We report the case of a 43-year-old male patient presenting for neuro
      ophthalmologic and uveitis consultation at Clermont-Ferrand University Medical
      Center for a reduction in visual acuity in his right eye. Two months previously,
      the patient had complained of decreased hearing on the left, which remained
      undiagnosed. Fundus examination and fluorescein angiogram showed the appearance
      of vasculitis with papillitis and a choroidal plaque. TPHA-VDRL serology was
      positive in blood and cerebrospinal fluid. Internal medicine work-up revealed
      many associated abnormalities: hyperhomocysteinemia, positive anticardiolipin
      antibody, positive anti-beta2GP1 antibodies, increased partial thromboplastin
      time not corrected by the addition of control plasma, presence of an anti
      prothrombinase antibody, positive activated protein C resistance. ENT examination
      showed a left harmonic vestibular syndrome; audiography showed a sensorineural
      hearing loss of -40 dB. The patient received treatment for neurosyphilis, which
      led to the disappearance of the vasculitis, the choroidal plaque and the
      papillitis. From an ENT standpoint, the vestibular syndrome and the left
      vestibular areflexia resolved. The audiogram improved, with persistence of left
      hearing loss (about -20 dB) with useful speech intelligibility. Immunologic
      abnormalities had also disappeared. Our case illustrates the protean
      presentations of syphilis and its possible association with sensorineural
      deafness and immunological abnormalities.

PMID- 23541534
TI  - [Imaging of the iridocorneal angle in glaucoma].
AB  - Iridocorneal angle assessment is essential in glaucoma diagnosis and management,
      and gonioscopy remains the clinical reference standard for its evaluation.
      However, performance and interpretation of gonioscopy requires experience and has
      several limitations. Ultrasound biomicroscopy (UBM) and more recently anterior
      segment OCT (AS-OCT) and Scheimpflug camera have contributed to a better
      understanding of the mechanisms of angle-closure, screening of patients at risk
      for angle-closure glaucoma, and understanding of angle structures in secondary
      open angle glaucomas. Rapid and non-contact, AS-OCT has made this analysis easier
      than with UBM, but it is limited by its weak penetration through iris and scleral
      tissues.

PMID- 23541532
TI  - Ubiquilin-2 (UBQLN2) binds with high affinity to the C-terminal region of TDP-43
      and modulates TDP-43 levels in H4 cells: characterization of inhibition by
      nucleic acids and 4-aminoquinolines.
AB  - Recently, it was reported that mutations in the ubiquitin-like protein ubiquilin
      2 (UBQLN2) are associated with X-linked amyotrophic lateral sclerosis (ALS), and
      that both wild-type and mutant UBQLN2 can co-localize with aggregates of C
      terminal fragments of TAR DNA binding protein (TDP-43). Here, we describe a high
      affinity interaction between UBQLN2 and TDP-43 and demonstrate that
      overexpression of both UBQLN2 and TDP-43 reduces levels of both exogenous and
      endogenous TDP-43 in human H4 cells. UBQLN2 bound with high affinity to both full
      length TDP-43 and a C-terminal TDP-43 fragment (261-414 aa) with KD values of
      6.2nM and 8.7nM, respectively. Both DNA oligonucleotides and 4-aminoquinolines,
      which bind to TDP-43, also inhibited UBQLN2 binding to TDP-43 with similar rank
      order affinities compared to inhibition of oligonucleotide binding to TDP-43.
      Inhibitor characterization experiments demonstrated that the DNA oligonucleotides
      noncompetitively inhibited UBQLN2 binding to TDP-43, which is consistent with
      UBQLN2 binding to the C-terminal region of TDP-43. Interestingly, the 4
      aminoquinolines were competitive inhibitors of UBQLN2 binding to TDP-43,
      suggesting that these compounds also bind to the C-terminal region of TDP-43. In
      support of the biochemical data, co-immunoprecipitation experiments demonstrated
      that both TDP-43 and UBQLN2 interact in human neuroglioma H4 cells. Finally,
      overexpression of UBQLN2 in the presence of overexpressed full length TDP-43 or C
      terminal TDP-43 (170-414) dramatically lowered levels of both full length TDP-43
      and C-terminal TDP-43 fragments (CTFs). Consequently, these data suggest that
      UBQLN2 enhances the clearance of TDP-43 and TDP-43 CTFs and therefore may play a
      role in the development of TDP-43 associated neurotoxicity.

PMID- 23541535
TI  - [Analysis of macular ganglion cell complex (GCC) with spectral-domain optical
      coherence tomography (SD-OCT) in glaucoma].
AB  - Early detection of ganglion cell loss is possible with new algorithms for the
      assessment of the Macular Ganglion Cell Complex (GCC) by SD-OCT. The various data
      acquisition protocols used by the various versions of software, as well as their
      accuracy and reproducibility, must be taken into account. Current results show
      similar ability to detect glaucoma as compared to Retinal Nerve Fiber Layer
      thickness (RNFL), with some limitations, possible artifacts, and interpretation
      pitfalls which must be taken into account. The role of the significance map and
      of various indices (Focal Loss Volume, Global Loss Volume, GCIPL minimum...);
      data obtained in the setting of various clinical entities (tilted disc,
      peripapillary atrophy, large and small optic discs, high myopia...); and
      detection of progression, especially in advanced glaucoma, underline the role of
      macular GCC analysis as a complementary method to peripapillary RNFL thickness.
      The diagnostic precision and better reproducibility of these new software
      protocols offer new perspectives in the detection and management of progression
      in various stages of the management of glaucomatous optic neuropathy.

PMID- 23541536
TI  - Infection control in cystic fibrosis: share and share alike.

PMID- 23541537
TI  - Chediak-Higashi syndrome: pathognomonic feature.

PMID- 23541538
TI  - 1 million community health workers in sub-Saharan Africa by 2015.

PMID- 23541539
TI  - Palestinian children in Israeli detention.

PMID- 23541540
TI  - Whole-genome sequencing to identify transmission of Mycobacterium abscessus
      between patients with cystic fibrosis: a retrospective cohort study.
AB  - BACKGROUND: Increasing numbers of individuals with cystic fibrosis are becoming
      infected with the multidrug-resistant non-tuberculous mycobacterium (NTM)
      Mycobacterium abscessus, which causes progressive lung damage and is extremely
      challenging to treat. How this organism is acquired is not currently known, but
      there is growing concern that person-to-person transmission could occur. We aimed
      to define the mechanisms of acquisition of M abscessus in individuals with cystic
      fibrosis. METHOD: Whole genome sequencing and antimicrobial susceptibility
      testing were done on 168 consecutive isolates of M abscessus from 31 patients
      attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In
      parallel, we undertook detailed environmental testing for NTM and defined
      potential opportunities for transmission between patients both in and out of
      hospital using epidemiological data and social network analysis. FINDINGS:
      Phylogenetic analysis revealed two clustered outbreaks of near-identical isolates
      of the M abscessus subspecies massiliense (from 11 patients), differing by less
      than ten base pairs. This variation represents less diversity than that seen
      within isolates from a single individual, strongly indicating between-patient
      transmission. All patients within these clusters had numerous opportunities for
      within-hospital transmission from other individuals, while comprehensive
      environmental sampling, initiated during the outbreak, failed to detect any
      potential point source of NTM infection. The clusters of M abscessus subspecies
      massiliense showed evidence of transmission of mutations acquired during
      infection of an individual to other patients. Thus, isolates with constitutive
      resistance to amikacin and clarithromycin were isolated from several individuals
      never previously exposed to long-term macrolides or aminoglycosides, further
      indicating cross-infection. INTERPRETATION: Whole genome sequencing has revealed
      frequent transmission of multidrug resistant NTM between patients with cystic
      fibrosis despite conventional cross-infection measures. Although the exact
      transmission route is yet to be established, our epidemiological analysis
      suggests that it could be indirect. FUNDING: The Wellcome Trust, Papworth
      Hospital, NIHR Cambridge Biomedical Research Centre, UK Health Protection Agency,
      Medical Research Council, and the UKCRC Translational Infection Research
      Initiative.

PMID- 23541542
TI  - The human myometrium differentially expresses mTOR signalling components before
      and during pregnancy: evidence for regulation by progesterone.
AB  - Emerging studies implicate the signalling of the mammalian target of rapamycin
      (mTOR) in a number of reproductive functions. To this date, there are no data
      regarding the expression of mTOR signalling components in the human myometrium
      during pregnancy. We hypothesized that mTOR-related genes might be differentially
      expressed in term or preterm labour as well as in labour or non-labour myometria
      during pregnancy. Using quantitative RT-PCR we demonstrate for first time that
      there is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm
      labouring myometria when compared to non-pregnant tissues taken from the same
      area (lower segment). We used an immortalized myometrial cell line (ULTR) as an
      in vitro model to dissect further mTOR signalling. In ULTR cells DEPTOR and
      Rictor had a cytoplasmic distribution, whereas mTOR and Raptor were detected in
      the cytoplasm and the nucleus, indicative of mTORC1 shuttling. Treatment with
      inflammatory cytokines caused only minor changes in gene expression of these
      components, whereas progesterone caused significant down-regulation. We performed
      a non-biased gene expression analysis of ULTR cells using Nimblegen human gene
      expression microarray (n=3), and selected genes were validated by quantitative RT
      PCR in progesterone treated myometrial cells. Progesterone significantly down
      regulated key components of the mTOR pathway. We conclude that the human
      myometrium differentially expresses mTOR signalling components and they can be
      regulated by progesterone. This article is part of a Special Issue entitled
      'Pregnancy and Steroids'. 

PMID- 23541543
TI  - Twin birth: an additional risk factor for poorer quality maternal interactions
      with very preterm infants?
AB  - BACKGROUND: Twin birth can be considered an additional risk factor for poor
      interactions between mothers and their very preterm (VP; <32 weeks' gestation)
      infants. AIMS: To explore if mothers of (VP) twins experience higher levels of
      stress than mothers of singletons and if mother-twin infant dyads experience
      poorer quality interactions. METHOD: Mothers of VP twin infants (N=17) were
      closely matched to mothers of VP singleton infants (N=17). Mother-infant
      interaction was assessed before discharge from hospital and during a home visit
      at three months corrected age using the Nursing Child Assessment Teaching Scale
      (NCATS). Mothers' responsiveness to their infants was assessed using the
      Responsivity subscale of the Home Observation for Measurement of the Environment
      (HOME) and mothers completed the Parenting Stress Index short form (PSI-SF).
      RESULTS: Mothers of twins had significantly lower HOME responsiveness scores
      (median 9 vs. 10) at three months corrected age and were more likely to have
      total PSI-SF scores in the clinical range (>90th percentile) compared to mothers
      of singletons (Fishers exact probability=0.05). Twin infants had lower mean Total
      Child Domain NCATS scores than singletons both at discharge (9.07 vs. 11.33) and
      at three months corrected age (13.18 vs. 15.71) indicating they were less
      responsive communicators. CONCLUSIONS: VP twins present a greater challenge than
      singletons as their mothers experience high levels of parenting stress. Although
      mothers appear to compensate for twin infants' poorer clarity of cues in a
      structured, one to one task, mothers of twins were less responsive than mothers
      of singletons in an unstructured setting.

PMID- 23541541
TI  - Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs.
AB  - Antiretroviral therapy for HIV infection needs lifelong access and strict
      adherence to regimens that are both expensive and associated with toxic effects.
      A curative intervention will be needed to fully stop the epidemic. The failure to
      eradicate HIV infection during long-term antiretroviral therapy shows the
      intrinsic stability of the viral genome in latently infected CD4T cells and other
      cells, and possibly a sustained low-level viral replication. Heterogeneity in
      latently infected cell populations and homoeostatic proliferation of infected
      cells might affect the dynamics of virus production and persistence. Despite
      potent antiretroviral therapy, chronic immune activation, inflammation, and
      immune dysfunction persist, and are likely to have important effects on the size
      and distribution of the viral reservoir. The inability of the immune system to
      recognise cells harbouring latent virus and to eliminate cells actively producing
      virus is the biggest challenge to finding a cure. We look at new approaches to
      unravelling the complex virus-host interactions that lead to persistent infection
      and latency, and discuss the rationale for combination of novel treatment
      strategies with available antiretroviral treatment options to cure HIV.

PMID- 23541544
TI  - Migration of fenestrated aortic stent grafts.
AB  - OBJECTIVE: This article reports the incidence, timing, and related sequelae for
      proximal and distal migration of the Zenith Fenestrated AAA Endovascular Graft
      (Cook Medical, Bloomington, Ind) used to treat abdominal aortic aneurysms.
      METHOD: A prospectively maintained database at a tertiary referral hospital was
      used to identify 83 patients who underwent endovascular repair using the Zenith
      fenestrated stent graft. Inclusion criteria included a postoperative computed
      tomography (CT) scan within 6 weeks of implantation and at least one additional
      follow-up CT scan (>5 months) available electronically at our institution.
      Eligible patients underwent assessment of stent graft migration using a CT-based
      central luminal line (CLL) technique. The proximal and distal margins of the
      stent graft were measured using CLLs relative to vascular landmarks on all
      available follow-up CT scans. Migration was defined as stent graft movement >=4
      mm. RESULTS: Fifty-five patients were included in this study, mean age was 74 +/-
      7 years, and 89% were men. Mean preoperative aneurysm diameter was 67 +/- 9 mm.
      In these 55 patients, fenestrations were applied to 162 target vessels with the
      commonest design accommodating two renal arteries (RAs) and the superior
      mesenteric artery (SMA). Median follow-up was 24 (range, 5-97) months; 80% of
      patients (n = 44) had both the proximal and two distal attachment sites assessed
      for evidence of migration. Twelve iliac limbs in 11 patients were excluded from
      analysis due to occlusion of one internal iliac artery precluding CLL assessment
      (n = 7), or image quality issues (n = 5). Using CLLs and based on those patients
      who exhibited migration, the median proximal and distal migration distances were
      +5.0 (range, +4.0 to +8.1) mm and -5.0 (range, -4.3 to -21.3) mm, respectively.
      Kaplan-Meier analysis for proximal migration revealed migration rates of 14% and
      22% at 12 and 36 months, respectively. Distal migration rates were lower at 3%
      and 8%, respectively. There have been no incidences of late rupture or open
      conversion. Of the patients with proximal migration, two patients lost a single
      target vessel (two RAs) and three patients were reported to have target vessel
      stenosis (two SMAs, one RA). These cases did not require reintervention.
      CONCLUSIONS: Both suprarenal fabric extension and visceral artery stenting are
      known to provide additional fixation for fenestrated aortic stent grafts. Despite
      this, minor proximal migration still occurs in up to one quarter of fenestrated
      endovascular repair patients by 4 years. We believe this is mainly due to the
      engagement of the barbs of the anchoring stent. Distal migrations occur with
      lower frequency.

PMID- 23541545
TI  - A nationwide survey of vascular surgery trainees reveals trends in operative
      experience, confidence, and attitudes about simulation.
AB  - OBJECTIVE: There is mounting evidence supporting the benefit of surgical skills
      training in a simulated environment. However, the use of simulation in vascular
      surgery has been limited, and its value has been poorly understood. Access to
      simulation is presumed to be a major barrier to its widespread implementation.
      While a great deal of discussion is taking place at the national level, input
      from current trainees has not been obtained. METHODS: The Association of Program
      Directors in Vascular Surgery Committee on Education and Simulation sent a survey
      to all vascular surgical trainees assessing access to vascular simulation, the
      perceived value of simulation, and expectations for the future. Data were
      analyzed for junior (postgraduate year <= 4; n = 73) and senior (postgraduate
      year >= 5; n = 110) level and program type (traditional = 5 + 2/4 + 2; integrated
      = 0 + 5). RESULTS: A total of 183 of 326 (56%) trainees completed the survey, 72
      (0-5), 5 (4+2), 111 (5+2), respectively. Of the respondents, 86% believe there is
      educational value in simulation. Cadaver dissections, followed by peripheral
      endovascular simulators and endovascular aortic aneurysm repair simulators, were
      ranked the most valuable tools by seniors, while anastomotic models are valued
      most by juniors, followed by cadavers and endosimulators. Fifty-six percent of
      programs currently offer simulation training, most commonly in the form of
      peripheral endovascular simulators (70%), anastomotic models (58%), or
      endovascular aortic aneurysm repair simulation (53%). Senior residents are more
      likely than juniors to have attended outside simulation courses (37% vs 19%).
      Overall, 57% of trainees expect that technical skills assessment will be
      incorporated into the certification process, and 52% endorse skills assessment
      for certification. CONCLUSIONS: Trainees report limited operative experience and
      confidence, and confidence levels are improved for a number of index procedures
      among those trainees with access to simulation. Trainees endorse the use of
      simulation to augment their surgical training, and a significant proportion of
      them already have access to it. These data support a perceived need and utility
      for implementation of a standardized simulation curriculum in vascular surgical
      training.

PMID- 23541546
TI  - Vasospasm as a cause for claudication in athletes with external iliac artery
      endofibrosis.
AB  - BACKGROUND: Exercise-induced external iliac artery endofibrosis (EIAE) is rare
      and has been described primarily in endurance male cyclists. Clinically, it
      presents as claudication during maximal exercise with quick resolution after
      exercise. Most patients have fibrotic changes within the external iliac artery
      (EIA). We describe our experience with EIAE and propose a hypothesis for the
      mechanism involved in the associated claudication. METHODS: This was a
      retrospective review of athletes who presented with symptomatic EIAE requiring
      operative repair between 2001 and 2010. Data collected included demographic
      information, initial presentation, type of exercise, repair, and long-term
      outcome. Diagnostic studies consisted of duplex evaluation, modified exercise
      treadmill test, and angiography. RESULTS: Eight women, presented with symptomatic
      EIAE. Two had bilateral EIAE. All were endurance athletes (three cyclists, one
      runner, and four were cyclists and runners). Median age at presentation was 42.5
      years (range, 39-60 years). Median duration of symptoms was 5.5 years (range, 2
      15 years). Diagnosis was confirmed with an exercise treadmill test modified to
      accommodate these patients' high level of conditioning and unmask the
      claudication. In the most recent two patients, marked EIA vasospasm was noted
      after exercise by duplex scanning. All patients were treated with EIA vein patch
      angioplasty. Follow-up ranged from 1 to 10 years. All had a normal result on the
      modified exercise treadmill test and resumed their athletic activities
      postoperatively. CONCLUSIONS: This series highlights a possible mechanism to
      explain the claudication associated with EIAE. Vasospasm may be more important
      than wall thickening for the reduction of blood flow during extreme exercise in
      affected athletes. Routine duplex ultrasound imaging to measure EIA diameter and
      flow velocities before and after maximal exercise is needed to confirm this
      phenomenon.

PMID- 23541547
TI  - Risk factors for readmission after lower extremity procedures for peripheral
      artery disease.
AB  - OBJECTIVE: As pressure to contain health care costs increases, there has been
      greater scrutiny of readmissions in the vascular surgery population. The
      objective of this study was to evaluate postoperative readmissions after open and
      endovascular lower extremity (LE) procedures for peripheral artery disease (PAD).
      METHODS: A retrospective cohort study was performed of elective adult inpatients
      with PAD and LE procedures which were selected from the Health Facts database
      (Cerner Corporation, Kansas City, Mo) between October 2008 and December 2010
      using International Classification of Disease, 9th Clinical Modification
      diagnosis codes (claudication, rest pain, and ulceration/gangrene) and procedure
      codes for LE revascularization (endovascular and open). Multivariable logistic
      regression and chi(2) were used to compare patients who received endovascular and
      open procedures. The Charlson Comorbidity Index, comorbid diagnoses, and
      laboratory results were used to adjust for confounding. The main outcome measure
      evaluated was readmission <= 30 days of discharge. RESULTS: Of 463,362 index
      admissions, 16,574 patients were identified with a diagnosis of PAD. Combining
      PAD with elective LE procedures during the index admission, 777 underwent open
      and 681 underwent endovascular procedures. Unadjusted readmission rates for open
      and endovascular procedures for claudication, rest pain, and ulceration/gangrene
      were 10.2% vs 11.3% (P = .69), 14.0% vs 18.2% (P = .43), and 21.1% vs 19.5% (P =
      .69), respectively. Readmission increased by the severity of the diagnosis for
      open and endovascular procedures (P = .0006). Men comprised 58% of the cohort;
      readmission rates were not statistically different by sex (P = .19). Race was not
      associated with procedure performed (P = .16), but nonwhite race was associated
      with more severe PAD (P < .0001). After adjusting for race, sex, comorbidities,
      length of stay, and laboratory values outside of normal reference ranges, the
      association between an endovascular procedure and readmission was not
      statistically significant (odds ratio, 1.28; 95% confidence interval, 0.94-1.75).
      CONCLUSIONS: Less invasive endovascular procedures were not associated with
      decreased readmission rates compared with open surgery. The overall readmission
      rate for claudicant patients was 10.7%, which was unexpectedly high. Predictors
      of readmission included male sex, longer hospital stays, hospital infection,
      elevated aspartate aminotransferase, and high numbers of medications ordered and
      dispensed. Further examination exploring reasons for readmission are required to
      decrease readmission rates in the vascular surgery population.

PMID- 23541548
TI  - The importance of socioeconomic factors for compliance and outcome at screening
      for abdominal aortic aneurysm in 65-year-old men.
AB  - OBJECTIVE: To evaluate compliance with screening and prevalence of abdominal
      aortic aneurysm (AAA) in relation to background data regarding area-based
      socioeconomic status. METHODS: Our department annually invites 4300 65-year-old
      men from the city of Malmo and 15 neighboring municipalities to ultrasound AAA
      screening. In a cross-sectional cohort study, compliance and AAA prevalence among
      8269 men were related to background socioeconomic data such as mean income,
      proportion of immigrants, percentage of subjects on welfare, smoking habits, and
      unemployment rate in the different municipalities. The 10 different
      administrative areas in Malmo were evaluated separately. RESULTS: Compliance with
      screening in the entire area was 6630/8269 (80.2%) but varied between 64.4% and
      89.3% in different municipalities (P < .001). In univariate analysis, compliance
      increased with increasing mean income (r = 0.873; P < .001) but decreased with
      increasing proportion of immigrants (r = -0.685; P =.005) and subjects on welfare
      (r = -0.698; P = .004). Compliance in 10 different administrative parts of Malmo
      (P = .002) also increased with increasing mean income (r = 0.948; P < .001), and
      decreased with increasing proportion of immigrants (r = -0.650; P = .042) and
      increasing unemployment rate (r = -0.796; P = .006). Altogether, 117 (1.8%) AAAs
      were found, the prevalence differing between both different municipalities (P
      =.003) and the 10 different administrative parts of Malmo (P =.02). The
      prevalence of AAA in the 10 administrative parts of Malmo increased with
      increasing percentage of smokers (r = 0.784; P = .007), percentage of immigrants
      (r = 0.644; P = .044), and unemployment rate (r = 0.783; P =.007) but decreased
      with increasing mean income (r = -0.754; P = .012). CONCLUSIONS: Compliance with
      ultrasound screening for AAA differed between different geographical areas. In
      areas with low socioeconomic status, compliance rates were lower, whereas AAA
      prevalence was higher. The identification of contextual factors associated with
      low compliance is important to be able to allow targeted actions to increase
      efficacy of ultrasound screening for AAA. Targeted actions to increase compliance
      in those areas are being scientifically investigated and implemented.

PMID- 23541549
TI  - Differentiating transmural from transanastomotic prosthetic graft
      endothelialization through an isolation loop-graft model.
AB  - BACKGROUND: In humans, transanastomotic endothelial outgrowth onto the surface of
      prosthetic vascular grafts is limited to the immediate perianastomotic region,
      even after years of implantation. In contrast, continual transanastomotic
      outgrowth together with short graft lengths has led to early endothelial
      confluence in most animal models pre-empting endothelialization through
      transmural capillary sprouting. We describe an isolation loop-graft model that
      clearly separates these distinctly different events. METHODS: Baseline
      transanastomotic endothelialization was assessed by implanting low-porosity
      expanded polytetrafluoroethylene grafts (ePTFE; internal diameter 1.7 mm;
      internodal distance 15-25 MUm; 14.2 +/- 1.6 mm long) for 2, 4, and 6 weeks (n =
      6/time point) in the abdominal aorta of Wistar rats. High-porosity polyurethane
      (internal diameter 1.7 mm-150 MUm pore size) grafts were then interposed
      ("welded") into the midsection of the ePTFE grafts for 2, 4, 6, and 8 weeks (n =
      6/time point). Looping the interposition grafts increased their length to 70.3 +/
      8.3 mm. After implantation periods of 6, 8, 12, and 24 weeks (n = 8/time point)
      isolation loop grafts were analyzed by light, immune-fluorescence (CD31) and
      scanning electron microscopy, and endothelialization was expressed as maximal
      transanastomotic endothelial outgrowth (I(max)), mean transanastomotic outgrowth
      (I(mean)), and segmental graft coverage (GSE). RESULTS: Transanastomotic
      outgrowth slowed down between 2 and 6 weeks of implantation (proximal: [I(max)
      from 0.9 +/- 0.5 to 0.3 +/- 0.3 mm/wk; P < .04; I(mean) from 0.3 +/- 0.1 to 0.2
      +/- 0.1 mm/wk; nonsignificant (NS)]; distal: [I(max) from 0.7 +/- 0.3 to 0.3 +/-
      0.2 mm/wk; P < .02; I(mean) from 0.3 +/- 0.2 to 0.2 +/- 0.0 mm/wk; NS]) but
      remained constant thereafter (I(max) = 0.5 +/- 0.2 mm/wk; I(mean) = 0.4 +/- 0.2
      mm/wk at 24 weeks NS). In straight composite grafts, the ePTFE separation zones
      were too short to isolate transmural ingrowth beyond week 4. In contrast, a broad
      endothelial-free separation zone was preserved in all looped composite grafts
      even after half a year of implantation (25.9 +/- 5.9 vs 8.7 +/- 4.9 mm proximally
      and 21.9 +/- 13.4 vs 12.3 +/- 6.2 mm distally at 6 and 24 weeks, respectively).
      Ninety-three percent of patent loop-grafts showed isolated transmural midgraft
      endothelium after 4 weeks and 97% after 6 weeks. Midgraft preconfluence was
      reached by 6 weeks (GSE = 55 +/- 45%) and confluence between week 12 and 24 (GSE
      = 95.0 +/- 10.0% and 84.0 +/- 30.13%). The subintimal thickness stayed constant
      with a nonsignificant trend toward regression (91.8 +/- 93.9 mm vs 71.4 +/- 59.4
      mm at 6 and 24 weeks, respectively; NS). CONCLUSIONS: Transmural
      endothelialization can be clearly distinguished from transanastomotic outgrowth
      in a high throughput rat model. A looped interposition graft model provides
      sufficient isolation length to separate the two events for up to half a year and
      does not result in an increase in intimal hyperplasia. CLINICAL RELEVANCE:
      Although the mode of graft deployment has changed over the years, the problem of
      an absent surface endothelium remains, whether small- to medium-diameter grafts
      are surgically implanted or placed endovascularly as "covered stents." In
      contrast to humans, most animal models experience progressive transanastomotic
      endothelial outgrowth. Together with graft lengths that were too short, the
      clinically irrelevant transanastomotic endothelialization inadvertently led to
      early endothelial confluence in the vast majority of experimental vascular graft
      studies pre-empting or concealing alternative modes of endothelialization. The
      isolation loop-graft model we propose allows the long-term differentiation of the
      different modes of endothelialization in a small animal screening model.

PMID- 23541550
TI  - Impact of hospital volume and type on outcomes of open and endovascular repair of
      descending thoracic aneurysms in the United States Medicare population.
AB  - OBJECTIVE: Favorable outcomes of thoracic endovascular aortic repair (TEVAR)
      compared with open repair for descending thoracic aortic aneurysms (DTAs) have
      led to increasing TEVAR use. We evaluated the effect of case volume and hospital
      teaching status on clinical outcomes of intact DTA repair. METHODS: The Medicare
      Provider Analysis and Review (MEDPAR) data set (2004 to 2007) was queried to
      identify open repair or TEVAR for DTA. Hospitals were stratified by DTA volume
      into high volume (HV; >= 8 cases/y) or low volume (LV; <8 cases/y) and teaching
      or nonteaching. The effect of hospital variables on the primary study end point
      of 30-day mortality and secondary end points of 30-day complications and long
      term survival after open repair and TEVAR DTA repair were studied using
      univariate testing, multivariable regression modeling, Kaplan-Meier survival
      analysis, and Cox proportional hazards regression modeling. RESULTS: We
      identified 763 hospitals performing 3554 open repairs and 3517 TEVARs. Overall
      DTA repair increased (P < .01) from 1375 in 2004 to 1987 in 2007. The proportion
      of hospitals performing open repair significantly decreased from 95% in 2004 to
      57% in 2007 (P < .01), whereas those performing TEVAR increased (P < .01) from
      24% to 76%. Overall repair type shifted from open (74% in 2004, the year before
      initial commercial availability of TEVAR) to TEVAR (39% open in 2007; P < .01).
      The fraction of open repairs at LV hospitals decreased from 56% in 2004 to 44% in
      2007 (P < .01), whereas TEVAR increased from 24% in 2004 to 51% in 2007 (P <
      .01). Overall mortality during the study interval for open repair was 15% at LV
      hospitals vs 11% at HV hospitals (P < .01), whereas TEVAR mortality was similar,
      at 3.9% in LV vs 5.5% in HV hospitals (P = .43). LV was independently associated
      with increased mortality after open repair (odds ratio, 1.4; 95% confidence
      interval, 1.1-1.8; P < .01) but not after TEVAR. There was no independent effect
      of hospital teaching status on mortality or complications after open repair or
      TEVAR repair. CONCLUSIONS: The total number of DTA repairs has significantly
      increased. Operative mortality for TEVAR is independent of hospital volume and
      type, whereas mortality after open surgery is lower at HV hospitals, suggesting
      that TEVAR can be safely performed across a spectrum of hospitals, whereas open
      surgery should be performed only at HV hospitals.

PMID- 23541551
TI  - Hypolipidemic and antioxidant properties of a polysaccharide fraction from
      Enteromorpha prolifera.
AB  - A polysaccharide fraction (EPF2) was obtained from the crude polysaccharides of
      Enteromorpha prolifera by a series isolation procedure. Monosaccharide components
      analysis indicated that EPF2 was composed of rhamnose, xylose, mannose, galactose
      and glucose in a molar ratio of 3.64:1.08:0.21:0.75:0.27. Hypolipidemic and
      antioxidant properties of EPF2 were investigated. The results showed that the
      hypolipidemic effect of EPF2 was in a concentration-dependent fashion and the
      prior oral administration of EPF2 (300 mg/kg body weight) exhibited considerable
      effect which could bear comparison with that of simvastatin. Moreover,
      administration of EPF2 could significantly enhance the activities of endogenous
      antioxidant enzymes and lowered the content of maleic dialdehyde (MDA) in serum.
      The results suggested that EPF2 had a high hypolipidemic activity and this
      activity might be attributed to its antioxidant potential.

PMID- 23541552
TI  - Sericins exhibit ROS-scavenging, anti-tyrosinase, anti-elastase, and in vitro
      immunomodulatory activities.
AB  - Some biological properties of Bombyx mori sericins from twenty strains were
      investigated, fourteen fed with artificial diet, two with fresh mulberry leaves
      and four with both diets. Sericin exhibited ROS-scavenging, anti-tyrosinase and
      anti-elastase properties, the strain significantly influenced these properties,
      while diet only influenced the anti-tyrosinase activity. Sericins were clustered
      into 5 groups and one sericin from each group was further studied: sericins
      showed anti-proliferative activity on in vitro stimulated peripheral blood
      mononuclear cells; some strains decreased in vitro secretion of IFNgamma, while
      no effects were observed on TNFalpha and IL10 release. Therefore, a mixture of
      sericins extracted from the most promising strains may be useful for
      dermatological and cosmetic use.

PMID- 23541553
TI  - Detection and analysis of amorphous aggregates and fibrils of cytochrome c in the
      presence of phenolic acids.
AB  - Cytochrome c (cyt c) exists as a partially unfolded intermediate at 45 mM gallic
      acid (GA) possessing disrupted secondary structure, altered Trp environment and
      high ANS binding. Increasing the concentration of either GA or ferulic acid (FA)
      up to 50 mM results in cyt c aggregation as confirmed by shift in Congo red,
      increase thioflavin T, decrease ANS and Trp fluorescence. SEM confirmed the
      formation of fibrils and amorphous aggregates of cyt c in presence of 50 mM FA
      and GA respectively. Single cell gel electrophoresis establishes very less
      probability of this noble protein to cause misfolding and aggregation-prone
      diseases.

PMID- 23541554
TI  - Wood plastic composite using graphene nanoplatelets.
AB  - This article presents the preparation and characterization of wood
      flour/polypropylene (PP) composites filled with graphene nanoplatelets (GNPs).
      The effects of GNPs, as reinforcing agent, on the mechanical and physical
      properties were also investigated. In order to increase the interphase adhesion,
      maleic anhydride grafted polypropylene (MAPP) was added as a coupling agent to
      all the composites studied. The morphology of the specimens was characterized
      using scanning electron microscopy (SEM) technique. The results of strength
      measurements indicated that when 0.8 wt.% GNPs were added, tensile and flexural
      properties reached their maximum values. At high levels of GNPs loading (3-5
      wt.%), increased population of GNPs leads to agglomeration and stress transfer
      gets blocked. The addition of GNPs filler moderately increased the impact
      strength of composites. Addition of GNPs decreased the average water uptake and
      thickness swelling by 35% and 30%, respectively, compared to the control sample
      (without GNPs). It was observed that the composites filled with GNPs decomposed
      at higher temperatures compared to the pure PP and control. In all cases, the
      degradation temperatures shifted to higher values after the addition of GNPs. The
      improvement of physical and mechanical properties of composites confirmed that
      GNPs have good reinforcement and the optimum effect of GNPs was achieved at 0.8
      wt.%.

PMID- 23541555
TI  - Extraction optimization of carbohydrate compound from Huangqi using orthogonal
      design.
AB  - The effect of extraction time, extraction temperature and time on the yield of
      Huangqi carbohydrate compound (HQCC) was investigated using single factor and
      orthogonal experiment design. The influence by the parameters on the extraction
      yields of carbohydrate compound decreased in the order of: C (extraction
      number)>A (extraction time)>B (extraction temperature) according to the R values.
      Based on this analysis, and considering the carbohydrate compound extraction
      efficiency, the cost of energy and the feasibility of experiment, the optimum
      conditions of extraction were therefore determined as follows: extraction time
      120min, extraction temperature 80 degrees C, and extraction number 4. Oral
      administration of HQCC reduced lipid peroxidation level and enhanced antioxidant
      enzymes activities in gastric mucosa. In addition, HQCC reduced the serum IL-8
      and TNF-alpha levels. In conclusion, these data reveal that HQCC promotes
      regeneration of damaged gastric mucosa, probably through its antioxidative
      mechanism.

PMID- 23541556
TI  - Microbead design for sustained drug release using four natural gums.
AB  - Four natural gums, namely albizia, cissus, irvingia and khaya gums have been
      characterized and evaluated as polymers for the formulation of microbeads for
      controlled delivery of diclofenac sodium. The natural gums were characterized for
      their material properties using standard methods. Diclofenac microbeads were
      prepared by ionotropic gelation using gel blends of the natural gums and sodium
      alginate at different ratios and zinc chloride solution (10%w/v) as the
      crosslinking agent. The microbeads were assessed using SEM, swelling
      characteristics, drug entrapment efficiencies and release properties. Data
      obtained from in vitro dissolution studies were fitted to various kinetic
      equations to determine the kinetics and mechanisms of drug release, and the
      similarity factor, f2, was used to compare the different formulations. The
      results showed that the natural gum polymers varied considerably in their
      material properties. Spherical and discrete microbeads with particle size of 1.48
      2.41 MUm were obtained with entrapment efficiencies of 44.0-71.3%w/w. Drug
      release was found to depend on the type and concentration of polymer gum used
      with formulations containing gum:alginate ratio of 3:1 showing the highest
      dissolution times. Controlled release of diclofenac was obtained over for 5h.
      Drug release from the beads containing the polymer blends of the four gums and
      sodium alginate fitted the Korsmeyer-Peppas model which appeared to be dependent
      on the nature of natural gum in the polymer blend while the beads containing
      alginate alone fitted the Hopfenberg model. Beads containing albizia and cissus
      had comparable release profiles to those containing khaya (f2>50). The results
      suggest that the natural gums could be potentially useful for the formulation
      controlled release microbeads.

PMID- 23541557
TI  - Mechanical stretch changes coronary artery fibroblasts function by upregulating
      HSF1 protein expression.
AB  - The study is designed to investigate effect of mechanical stretch on the function
      of fibroblast cells. Human coronary artery fibroblasts were cultured. They were
      divided into two groups: stretch group (stretch for 24h) and no-stretch group
      (did not stretch). ELISA analysis was used for detection of collagen secretion.
      CCK-8 method was used for detection of cells proliferation. RT-PCR method was
      used for detection of MMP, TIMP, IL-6, alpha-SMA, HSF1 and HSP70 mRNA expression.
      Western-blotting method was used for detection of HSF1 protein expression.
      Results showed that cells proliferation in stretch group was stronger than that
      in no-stretch group. Hydroxyproline secretion in stretch group was more than that
      in no-stretch group. MMP-9/TIMP, alpha-SMA, IL-6, HSF1 and HSP70 in stretch group
      was higher than those in no-stretch group. Western-blotting analysis showed that
      HSF1 protein expression was upregulated in stretch group. It can be concluded
      that mechanical stretch changed human coronary artery fibroblasts cells
      proliferation, collagen formation, the secretion of inflammatory factor possibly
      by upregulating HSF1 protein expression.

PMID- 23541558
TI  - WITHDRAWN: Elucidation of structural condensation in lignin of eastern
      cottonwood.
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- 23541559
TI  - Polysaccharide extraction from Spirulina sp. and its antioxidant capacity.
AB  - To optimize polysaccharide extraction from Spirulina sp., the effect of solid-to
      liquid ratio, extraction temperature and time were investigated using Box-Behnken
      experimental design and response surface methodology. The results showed that
      extraction temperature and solid-to-liquid ratio had a significant impact on the
      yield of polysaccharides. A polysaccharides yield of around 8.3% dry weight was
      obtained under the following optimized conditions: solid-to-liquid ratio of 1:45,
      temperature of 90 degrees C, and time of 120 min. The polysaccharide extracts
      contained rhamnose, which accounted for 53% of the total sugars, with a phenolic
      content of 45 mg GAE/g sample.

PMID- 23541560
TI  - Flocculation characteristics and biodegradation studies of Gum ghatti based
      hydrogels.
AB  - Biodegradable flocculants of Gum ghatti (Gg) with acrylamide (AAm) were prepared
      through graft co-polymerization technique using potassium persulphate (KPS)
      ascorbic acid (ABC) redox pair as initiator and N,N'-methylene-bis-acrylamide
      (MBA) as a crosslinker. Gg-cl-poly(AAm) was found to exhibit pH and temperature
      responsive swelling behavior. Maximum flocculation efficiency of Gg-cl-poly(AAm)
      was observed with 15 mg L(-1) polymer dose in acidic medium at 50 degrees C.
      Biodegradation studies of Gg and Gg-cl-poly(AAm) were done using composting
      method. Gg was found to degrade within 20 days, whereas, Gg-cl-poly(AAm) was
      found to degrade 88.18% within 60 days. Different stages of bio-degradation were
      characterized through FT-IR and SEM techniques.

PMID- 23541561
TI  - Biochemical characterization of recombinant cinnamoyl CoA reductase 1 (Ll-CCRH1)
      from Leucaena leucocephala.
AB  - Recombinant cinnamoyl CoA reductase 1 (Ll-CCRH1) protein from Leucaena
      leucocephala was overexpressed in Escherichia coli BL21 (DE3) strain and purified
      to apparent homogeneity. Optimum pH for forward and reverse reaction was found to
      be 6.5 and 7.8 respectively. The enzyme was most stable around pH 6.5 at 25
      degrees C for 90 min. The enzyme showed Kcat/Km for feruloyl, caffeoyl, sinapoyl,
      coumaroyl CoA, coniferaldehyde and sinapaldehyde as 4.6, 2.4, 2.3, 1.7, 1.9 and
      1.2 (*10(6) M(-1) s(-1)), respectively, indicating affinity of enzyme for
      feruloyl CoA over other substrates and preference of reduction reaction over
      oxidation. Activation energy, Ea for various substrates was found to be in the
      range of 20-50 kJ/mol. Involvement of probable carboxylate ion, histidine, lysine
      or tyrosine at the active site of enzyme was predicted by pH activity profile.
      SAXS studies of protein showed radius 3.04 nm and volume 49.25 nm(3) with oblate
      ellipsoid shape. Finally, metal ion inhibition studies revealed that Ll-CCRH1 is
      a metal independent enzyme.

PMID- 23541563
TI  - Large-scale independent validation of the nuclear factor-kappa B p65 prognostic
      biomarker in prostate cancer.
AB  - PURPOSE: Over the last decade, we and others have uncovered a robust association
      between the nuclear localisation of nuclear factor-kappa B (NF-kappaB) p65,
      prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal
      was to validate these results in a large independent cohort of PCa patients who
      underwent radical prostatectomy. EXPERIMENTAL DESIGN: A set of 1826 fully
      annotated prostate cancers treated by radical prostatectomy were analysed in a
      tissue microarray (TMA) format for NF-kappaB p65 immunohistochemistry-based
      protein expression. We performed standard Cox proportional hazard regression
      models for follow-up data, bootstrap procedure for model internal validation,
      Harrell's concordance index for model discrimination and graphical assessment of
      predicted versus actual outcomes for model calibration. RESULTS: We observed a
      significant association between an increase in the nuclear frequency of NF-kappaB
      p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of
      metastases (P=0.001). NF-kappaB was found to be an independent predictor of BCR
      (P<0.001, Cox regression). However its contribution to the predictive accuracy of
      a multivariate model, which included preoperative PSA, Gleason score,
      extraprostatic extension, lymph node invasion, seminal vesicle involvement and
      surgical margin status, was modest. CONCLUSIONS: Our study offers validating
      results linking NF-kappaB p65 with disease progression using a large cohort of
      European men. However, the contribution of NF-kappaB to a post-surgical
      predictive model appears modest. Further validating work should focus on
      evaluating the contribution of NF-kappaB p65 in pre-treatment models.

PMID- 23541562
TI  - Obstructive sleep apnea and cognitive impairment: addressing the blood-brain
      barrier.
AB  - Increasing data support a connection between obstructive sleep apnea (OSA) and
      cognitive impairment but a causal link has yet to be established. Although
      neuronal loss has been linked to cognitive impairment, emerging theories propose
      that changes in synaptic plasticity can cause cognitive impairment. Studies
      demonstrate that disruption to the blood-brain barrier (BBB), which is uniquely
      structured to tightly maintain homeostasis inside the brain, leads to changes in
      the brain's microenvironment and affects synaptic plasticity. Cyclical
      intermittent hypoxia is a stressor that could disrupt the BBB via molecular
      responses already known to occur in either OSA patients or animal models of
      intermittent hypoxia. However, we do not yet know if or how intermittent hypoxia
      can cause cognitive impairment by mechanisms operating at the BBB. Therefore, we
      propose that initially, adaptive homeostatic responses at the BBB occur in
      response to increased oxygen and nutrient demand, specifically through regulation
      of influx and efflux BBB transporters that alter microvessel permeability. We
      further hypothesize that although these responses are initially adaptive, these
      changes in BBB transporters can have long-term consequences that disrupt the
      brain's microenvironment and alter synaptic plasticity leading to cognitive
      impairment. 

PMID- 23541564
TI  - Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients
      with non-responsive tumours to epirubicin/cyclophosphamide (EC) +/- bevacizumab -
      results of the randomised GeparQuinto study (GBG 44).
AB  - BACKGROUND: We tested the oral mammalian target of rapamycin (mTOR) inhibitor
      everolimus in addition to paclitaxel in patients with HER2-negative tumours not
      responding to initial neoadjuvant cytotoxic and anti-angiogenic treatment.
      METHODS: Patients with primary HER2-negative tumours received four neoadjuvant
      cycles of epirubicin/cyclophosphamide (EC) with or without bevacizumab. Patients
      without clinical response were randomised to receive weekly paclitaxel (80
      mg/m(2)) with or without everolimus (5mg p.o. daily, after a step-wise dose
      escalation starting from 2.5mg bid) for 12 weeks before surgery. To detect an
      increase in pathological complete response (pCR; ypT0 ypN0) from 5% to 12.1%
      (odds ratio 2.62) 566 patients had to be recruited. The trial was stopped
      prematurely due to completion of accrual in the main study. FINDINGS: Of 1948
      patients initially starting neoadjuvant treatment 403 were randomised. A total of
      18 (4.6%) patients, 7 (3.6%) treated with paclitaxel and everolimus and 11 (5.6%)
      treated with paclitaxel alone had a pCR (odds ratio 0.36 (OR) (95% confidence
      interval (CI), 0.24-1.6) p=0.34). Overall response rate in breast and lymph nodes
      at surgery was 52.2% after paclitaxel plus everolimus and 61.7% after paclitaxel
      alone (p=0.063). Breast conserving treatment was performed in 54.4% of patients
      with the combination treatment and 61.9% with paclitaxel alone (p=0.20). Mucosal
      inflammation, thrombocytopenia, neutropenia, infection, and skin rash were more
      frequent when everolimus was added to paclitaxel. INTERPRETATION: Neoadjuvant
      therapy with everolimus and paclitaxel for patients with HER2-negative disease
      unresponsive to EC with or without bevacizumab did not improve the pCR rate. Long
      term outcome is awaited. FUNDING: Novartis, Roche, and Sanofi-Aventis.

PMID- 23541565
TI  - The PARAMOUNT study and the re-challenge chemotherapy issue in advanced non-small
      cell lung cancer.

PMID- 23541567
TI  - Re: Superiority of denosumab to zoledronic acid for prevention of skeletal
      related events: a combined analysis of three pivotal, randomised, phase 3 trials.

PMID- 23541568
TI  - Genetic deletion of the long isoform of the von Hippel-Lindau tumour suppressor
      gene product alters microtubule dynamics.
AB  - The von Hippel-Lindau tumour suppressor protein (pVHL) controls distinct cellular
      responses ranging from targeting hypoxia inducible factor alpha (HIFalpha)
      subunits for degradation and promotion of chromosomal stability to the regulation
      of microtubule dynamics. pVHL is produced in mammalian cells as a long and a
      short isoform, derived from alternate translational initiation sites in a single
      Vhl mRNA. However, it is unclear whether these isoforms have different cell
      biological activities that may represent different tumour suppressor activities
      of pVHL. Through a knock-in strategy to mutate the first translational initiation
      site from methionine to leucine (M1L) we have genetically deleted the pVHL long
      protein isoform in mice, allowing dissection of isoform-specific functions of
      pVHL. Vhl(M1L/M1L) mice exhibit no obvious phenotypic abnormalities. While
      numerous pVHL-mediated activities, including degradation of HIFalpha
      transcription factors, are unaffected, microtubule dynamics are altered in
      primary cells derived from Vhl(M1L/M1L) mice to an extent similar to that seen
      following complete loss of pVHL function. We conclude that the microtubule
      regulating function and the HIFalpha-regulating function of pVHL are separable
      activities mediated by different protein isoforms.

PMID- 23541566
TI  - Rare neuroendocrine tumours: results of the surveillance of rare cancers in
      Europe project.
AB  - Because of the low incidence, and limited opportunities for large patient volume
      experiences, there are very few relevant studies of neuroendocrine tumours
      (NETs). A large population-based database (including cancer patients diagnosed
      from 1978 to 2002 and registered in 76 population-based cancer registries [CRs]),
      provided by the project 'surveillance of rare cancers in Europe' (RARECARE) is
      used to describe the basic indicators of incidence, prevalence and survival of
      NETs, giving a unique overview on the burden of NETs in Europe. NETs at all
      cancer sites, excluding lung, were analysed in this study. In total over 20,000
      incident cases of NETs were analysed and a data quality check upon specific NETs
      was performed. The overall incidence rate for NETs was 25/1,000,000 and was
      highest in patients aged 65 years and older with well differentiated endocrine
      carcinomas (non-functioning pancreatic and gastrointestinal) (40 per 1,000,000).
      We estimated that slightly more than 100,000 people were diagnosed with NETs and
      still alive in EU27 at the beginning of 2008. Overall, NETs had a 5 year relative
      survival of 50%; survival was low (12%) for poorly differentiated endocrine
      carcinoma, and relatively high (64%) for well differentiated carcinoma (not
      functioning of the pancreas and digestive organs). Within NETs, endocrine
      carcinoma of thyroid gland had the best 5-year relative survival (82%). Because
      of the complexity and number of the different disciplines involved with NETs (as
      they arise in many organs), a multidisciplinary approach delivered in highly
      qualified reference centres and an international network between those centres is
      recommended.

PMID- 23541569
TI  - The impact of aspirin use on colorectal cancer patients.

PMID- 23541570
TI  - Response to letter commenting on paper EJC-D-12-01401: Use of aspirin post
      diagnosis in a cohort of patients with colorectal cancer and its association with
      all-cause and colorectal cancer specific mortality.

PMID- 23541571
TI  - High pretreatment serum lactate dehydrogenase level correlates with disease
      relapse and predicts an inferior outcome in locally advanced nasopharyngeal
      carcinoma.
AB  - PURPOSE: Here, we evaluate the prognostic effect of pretreatment serum lactate
      dehydrogenase (LDH) in locally advanced nasopharyngeal carcinoma (NPC). METHODS
      AND MATERIALS: Pretreatment serum samples from a randomized controlled trial,
      which contained 199 neoadjuvant chemoradiotherapy patients and 201 neoadjuvant
      concurrent chemoradiotherapy cases with locally advanced NPC, were collected and
      examined for LDH. With 5-year follow-up, the prognostic effect of pretreatment
      serum LDH was analysed by Kaplan-Meier analysis and multivariate Cox regression
      model. RESULTS: Three hundred and sixty-seven patients (91.75%) had a normal
      (109.0-245.0 U/L) pretreatment LDH level, compared to 33 cases (8.25%) that had a
      higher (>=245.0 U/L) LDH level. The mean and median pretreatment LDH levels of
      these 400 patients were 186.6 and 174.0 U/L (range, 83.0-751.0 U/L),
      respectively. Compared with the normal subset, elevated LDH level predicted an
      inferior 5-year overall survival (56.9% versus 76.8%, P=0.004), disease-free
      survival (DFS, 45.4% versus 64.7%, P=0.001), local relapse-free survival (76.1%
      versus 89.6%, P=0.019) and distant metastasis-free survival (DMFS, 54.3% versus
      72.2%, P=0.001). Multivariate analysis confirmed that the LDH level was an
      independent prognostic factor to predict death, disease progression, local
      relapse and distant metastasis. For the subgroup with normal LDH (median point of
      177.0 U/L), we detected an evident 5-year DFS (68.8% versus 59.5%, P=0.047) and
      DMFS advantage (77.3% versus 65.3%, P=0.016) in 109.0-177.0 U/L subset than that
      of 178.0-245.0 U/L subgroup. CONCLUSIONS: Serological LDH level was an
      independent prognostic factor for locally advanced NPC. Combining pretreatment
      LDH with TNM staging might lead to more accurate risk definition.

PMID- 23541572
TI  - Cell penetrating recombinant Foxp3 protein enhances Treg function and ameliorates
      arthritis.
AB  - Foxp3 is the master transcription factor for T regulatory (Treg) cell
      differentiation and function. This study aimed to test the therapeutic potential
      of cell penetrating recombinant Foxp3 protein in arthritis. Recombinant Foxp3
      protein was fused to a cell penetrating polyarginine (Foxp3-11R) tag to
      facilitate intracellular transduction. In vitro Foxp3-11R treated CD4(+) T cells
      showed a 50% increase in suppressive function compared with control protein
      treated cells. Severity of arthritis in Foxp3-11R treated mice was significantly
      reduced compared with those treated with a control protein. CD4(+) T cells of
      lymph nodes and spleen from Foxp3-11R treated mice showed increased levels of
      Foxp3 expression compared with those of a control protein treated. These results
      demonstrated that Foxp3-11R can enhance T cell suppressive function and
      ameliorate experimental arthritis and suggest that cell penetrating recombinant
      Foxp3 is a potentially useful agent in therapy of arthritis.

PMID- 23541573
TI  - Multielectrode array analysis of cerebrospinal fluid in Alzheimer's disease
      versus mild cognitive impairment: a potential diagnostic and treatment biomarker.
AB  - Pathological cerebrospinal fluid (CSF) alterations like changes in amyloid-beta1
      42 and tau protein concentration are typical in Alzheimer's disease (AD).
      However, it remains unclear, if the composition of known or unknown pathological
      factors in native CSF has a functional significance in AD. In this pilot study,
      we used multielectrode array (MEA) neurochips to determine whether CSF of
      individuals with AD (AD-CSF) may have distinct neurofunctional properties that
      may distinguish it from that of individuals with mild cognitive impairment (MCI) 
      a differential diagnosis of high clinical importance. MEAs are neuronal cultures
      coupled to a multisite electrical recording system with the ability to reflect
      pharmacological or toxicological alterations on the functional level of whole
      neuronal networks. Collective rhythmical electrical activity was substantially
      enhanced after exposure to CSF of cognitively healthy subjects (controls) and of
      MCI individuals (MCI-CSF) alike. However, this activity increment was
      significantly reduced when MEAs were exposed to AD-CSF compared to MCI-CSF.
      Moreover, following AD-CSF exposure, networks showed significantly enhanced burst
      durations and less synchronous bursting, respectively. Thus, AD-CSF and MCI-CSF
      could be distinguished by characteristic changes of the network firing pattern on
      MEAs. When data of MCI individuals and AD patients were pooled, the network
      suppression correlated significantly with the degree of cognitive decline. The
      findings of this pilot study may set the stage for a unique and straightforward
      diagnostic bioassay of AD with particular value in the differential diagnosis to
      MCI and as a much needed biomarker for clinical trials.

PMID- 23541574
TI  - Cessation of cyclic stretch induces atrophy of C2C12 myotubes.
AB  - Cyclic stretch of differentiated myotubes mimics the loading pattern of mature
      skeletal muscle. We tested a cell culture model of disuse atrophy by the
      cessation of repetitive bouts of cyclic stretch in differentiated C2C12 myotubes.
      Myotubes were subjected to cyclic strain (12%, 0.7 Hz, 1 h/d) on collagen-I
      coated Bioflex plates using a computer-controlled vacuum stretch apparatus
      (Flexcell Int.) for 2 (2dSTR) or 5 (5dSTR) consecutive days. Control cultures
      were maintained in the Bioflex plates without cyclic stretch for 2d or 5d.
      Additionally, some cultures were stretched for 2 d followed by cessation of
      stretch for 3d (2dSTR3dCES). Cyclic stretching (5dSTR) increased myotube diameter
      and overall myotube area by ~2-fold (P<0.05) compared to non-stretched controls,
      while cessation of stretch (2dSTR3dCES) resulted in ~80% smaller myotubes than
      5dSTR cells, and 40-50% smaller than non-stretched controls (P<0.05). Further,
      the calpain-dependent cleavage products of alphaII-spectrin (150 kDa) and talin
      increased (3.5-fold and 2.2-fold, respectively; P<0.05) in 2dSTR3dCES myotubes,
      compared to non-stretched controls. The 1h cyclic stretching protocol acutely
      increased the phosphorylation of Akt (+4.5-fold; P<0.05) and its downstream
      targets, FOXO3a (+4.2-fold; P<0.05) and GSK-3beta (+1.8-fold; P<0.05), which
      returned to baseline by 48 h after cessation of stretch. Additionally, nitric
      oxide production increased during stretch and co-treatment with the NOS
      inhibitor, l-NAME, inhibited the effects of stretch and cessation of stretch. We
      conclude that cessation of cyclic stretching causes myotube atrophy by activating
      calpains and decreasing activation of Akt. Stretch-induced myotube growth, as
      well as activation of atrophy signaling with cessation of stretch, are dependent
      on NOS activity.

PMID- 23541575
TI  - Recent advances in understanding the biochemical and molecular mechanism of
      diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a chronic disease characterized by proteinuria,
      glomerular hypertrophy, decreased glomerular filtration and renal fibrosis with
      loss of renal function. DN is the leading cause of end-stage renal disease,
      accounting for millions of deaths worldwide. Hyperglycemia is the driving force
      for the development of diabetic nephropathy. The exact cause of diabetic
      nephropathy is unknown, but various postulated mechanisms are: hyperglycemia
      (causing hyperfiltration and renal injury), advanced glycosylation products,
      activation of cytokines. In this review article, we have discussed a number of
      diabetes-induced metabolites such as glucose, advanced glycation end products,
      protein kinase C and oxidative stress and other related factors that are
      implicated in the pathophysiology of the DN. An understanding of the biochemical
      and molecular changes especially early in the DN may lead to new and effective
      therapies towards prevention and amelioration of DN.

PMID- 23541576
TI  - Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking.
AB  - Nucleoporin Nup98 is a component of the nuclear pore complex, and is important in
      transport across the nuclear pore. Many studies implicate nucleoporin in cancer
      progression, but no direct mechanistic studies of its effect in cancer have been
      reported. We show here that Nup98 specifically regulates nucleus-cytoplasm
      transport of galectin-3, which is a beta-galactoside-binding protein that affects
      adhesion, migration, and cancer progression, and controls cell growth through the
      beta-catenin signaling pathway in cancer cells. Nup98 interacted with galectin-3
      on the nuclear membrane, and promoted galectin-3 cytoplasmic translocation
      whereas other nucleoporins did not show these functions. Inversely, silencing of
      Nup98 expression by siRNA technique localized galectin-3 to the nucleus and
      retarded cell growth, which was rescued by Nup98 transfection. In addition, Nup98
      RNA interference significantly suppressed downstream mRNA expression in the beta
      catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to
      beta-catenin to inhibit transcriptional activity. Reduced expression of beta
      catenin target genes is consistent with the Nup98 reduction and the galectin-3
      nucleus translocation rate. Overall, the results show Nup98's involvement in
      nuclear-cytoplasm translocation of galectin-3 and beta-catenin signaling pathway
      in regulating cell proliferation, and the results depicted here suggest a novel
      therapeutic target/modality for cancers.

PMID- 23541577
TI  - Tespa1 protein is phosphorylated in response to store-operated calcium entry.
AB  - We previously reported that Tespa1 (thymocyte-expressed, positive selection
      associated gene 1) protein expressed in lymphocytes physically interacts with
      IP3R (Inositol 1,4,5-trisphosphate receptor), a Ca(2+) channel protein spanning
      endoplasmic reticulum (ER) membrane. However, the biochemical characterization of
      Tespa1 protein remains unknown. In this study, we have found that Tespa1 protein
      was posttranslationally modified upon intracellular Ca(2+) increase in
      thymocytes. Through the analyses using various inhibitors, store-operated Ca(2+)
      entry (SOCE) was found to be an essential factor for the Tespa1 protein
      modification induced by T cell receptor (TCR)-stimulation. Remarkably, the Ca(2+)
      dependent Tespa1 protein modification was restored by in vitro protein
      phosphatase treatment, indicating that this modification was due to
      phosphorylation. Moreover, we examined whether Ca(2+)-dependent phosphorylation
      of Tespa1 protein would affect the physical association between Tespa1 and IP3R
      proteins, revealing that physical association of these proteins is maintained
      regardless of the presence or absence of phosphorylation of Tespa1. In addition,
      KRAP protein which represents substantial amino acid sequence homology to Tespa1
      was also posttranslationally phosphorylated by intracellular Ca(2+) increase in
      HCT116 human colon cancer cells and HEK293 human embryonic kidney cells,
      suggesting that common signaling mechanism(s) may contribute to the molecular
      modification of Tespa1 and KRAP in different cellular processes. All these
      results suggested a novel molecular modification of Tespa1 and the existence of
      the regulatory pathway that SOCE affects the Tespa1-IP3R molecular complex.

PMID- 23541578
TI  - 3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus
      neoformans.
AB  - We have investigated the antifungal activity of the pyruvic acid analogue: 3
      bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and
      filamentous fungi was tested by standard spot tests or microdilution method. The
      human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory
      Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C.
      neoformans correlated with high intracellular accumulation of 3-BP and also with
      low levels of intracellular ATP and glutathione. Weak cytotoxicity towards
      mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug
      Resistance) network in the yeast Saccharomyces cerevisiae, are other properties
      of 3-BP that makes it a novel promising anticryptococcal drug.

PMID- 23541579
TI  - Extracellular heat shock protein A9 is a novel interaction partner of podoplanin
      in oral squamous cell carcinoma cells.
AB  - In previous studies, we have shown several lines of evidence that podoplanin
      (PDPN) plays an important role in cell adhesion via its association with
      extracellular components in neoplastic conditions, though there has been no trial
      to search for PDPN-interaction molecules in the extracellular milieu. To screen
      for those molecules, we performed proteomics-based analysis using liquid
      chromatography-tandem mass spectrometry followed by co-immunoprecipitation for
      PDPN in ZK-1, an oral squamous cell carcinoma (SCC) cell system whose cell
      membrane molecules were cross-linked with each other in their extracellular
      compartments, and we identified heat shock protein (HSP) A9 as one of the
      extracellular PDPN bound molecules. Effects of transient PDPN knockdown by siRNA
      in ZK-1 were also comparatively examined for cellular behaviors in terms of HSPA9
      expression and secretion. Finally, HSPA9 expression modes were
      immunohistochemically visualized in oral SCC tissue specimens. HSPA9 was secreted
      from ZK-1 cells, and the expression and secretion levels of HSPA9 gene and
      protein were well coordinated with those of PDPN. Immunohistochemically, HSPA9
      and PDPN were co-localized in ZK-1 cells and oral SCC foci, especially in the
      peripheral zone. In conclusion, the results indicate that HSPA9 secreted by oral
      SCC cells interacts with PDPN on their cell surface in an autocrine manner and
      regulates their growth and invasiveness.

PMID- 23541580
TI  - Lithium prevents early cytosolic calcium increase and secondary injurious calcium
      overload in glycolytically inhibited endothelial cells.
AB  - Cytosolic free calcium concentration ([Ca(2+)]i) is a central signalling element
      for the maintenance of endothelial barrier function. Under physiological
      conditions, it is controlled within narrow limits. Metabolic inhibition during
      ischemia/reperfusion, however, induces [Ca(2+)]i overload, which results in
      barrier failure. In a model of cultured porcine aortic endothelial monolayers
      (EC), we addressed the question of whether [Ca(2+)]i overload can be prevented by
      lithium treatment. [Ca(2+)]i and ATP were analysed using Fura-2 and HPLC,
      respectively. The combined inhibition of glycolytic and mitochondrial ATP
      synthesis by 2-desoxy-d-glucose (5mM; 2-DG) plus sodium cyanide (5mM; NaCN)
      caused a significant decrease in cellular ATP content (14+/-1 nmol/mg protein vs.
      18+/-1 nmol/mg protein in the control, n=6 culture dishes, P<0.05), an increase
      in [Ca(2+)]i (278+/-24 nM vs. 71+/-2 nM in the control, n=60 cells, P<0.05), and
      the formation of gaps between adjacent EC. These observations indicate that there
      is impaired barrier function at an early state of metabolic inhibition.
      Glycolytic inhibition alone by 10mM 2-DG led to a similar decrease in ATP content
      (14+/-2 nmol/mg vs. 18+/-1 nmol/mg in the control, P<0.05) with a delay of 5 min.
      The [Ca(2+)]i response of EC was biphasic with a peak after 1 min (183+/-6 nM vs.
      71+/-1 nM, n=60 cells, P<0.05) followed by a sustained increase in [Ca(2+)]i. A
      24-h pre-treatment with 10mM of lithium chloride before the inhibition of ATP
      synthesis abolished both phases of the 2-DG-induced [Ca(2+)]i increase. This
      effect was not observed when lithium chloride was added simultaneously with 2-DG.
      We conclude that lithium chloride abolishes the injurious [Ca(2+)]i overload in
      EC and that this most likely occurs by preventing inositol 3-phosphate-sensitive
      Ca(2+)-release from the endoplasmic reticulum. Though further research is needed,
      these findings provide a novel option for therapeutic strategies to protect the
      endothelium against imminent barrier failure.

PMID- 23541581
TI  - Evaluation of the in vitro and in vivo angiogenic effects of exendin-4.
AB  - Exendin-4, an analog of glucagon-like peptide (GLP)-1, has beneficial effects on
      cardiovascular disease induced by diabetes mellitus (DM). Recently, exendin-4 was
      reported to induce the proliferation of endothelial cells. However, its
      angiogenic effect on endothelial cells has not been clearly evaluated. Therefore,
      we investigated the effects of exendin-4 on the angiogenic process with respect
      to migration, sprouting, and neovascularization using in vitro and in vivo
      assays. Treatment with exendin-4 increased the migration of human umbilical vein
      endothelial cells (HUVECs) in in vitro scratch wound assays, as well as the
      number of lumenized vessels sprouting from HUVECs in in vitro 3D bead assays.
      These responses were abolished by co-treatment with exendin (9-39), a GLP-1
      receptor antagonist, which suggests that exendin-4 regulates endothelial cell
      migration and tube formation in a GLP-1 receptor-dependent manner. In an ex vivo
      assay, treatment of aortic rings with exendin-4 increased the sprouting of
      endothelial cells. Exendin-4 also significantly increased the number of new
      vessels and induced blood flow in Matrigel plugs in in vivo assays. Our results
      provide clear evidence for the angiogenic effect of exendin-4 in in vitro and in
      vivo assays and provide a mechanism underlying the cardioprotective effects of
      exendin-4.

PMID- 23541582
TI  - Hypoxia-inducible factor-1beta (HIF-1beta) is upregulated in a HIF-1alpha
      dependent manner in 518A2 human melanoma cells under hypoxic conditions.
AB  - Solid tumors include hypoxic areas due to excessive cell proliferation.
      Adaptation to low oxygen levels is mediated by the hypoxia-inducible factor (HIF)
      pathway promoting invasion, metastasis, metabolic alterations, chemo-resistance
      and angiogenesis. The transcription factor HIF-1, the major player within this
      pathway consists of HIF-1alpha and HIF-1beta. The alpha subunit is continuously
      degraded under normoxia and becomes stabilized under reduced oxygen supply. In
      contrast, HIF-1beta is generally regarded as constitutively expressed and being
      present in excess within the cell. However, there is evidence that the expression
      of this subunit is more complex. The aim of this study was to investigate the
      role of HIF-1beta in human melanoma cells. Among a panel of five different cell
      lines, in 518A2 cells exposed to the hypoxia-mimetic cobalt chloride HIF-1beta
      was rapidly elevated on protein level. Knockdown experiments performed under
      cobalt chloride-exposure and hypoxia revealed that this effect was mediated by
      HIF-1alpha. The non-canonical relationship between these subunits was further
      confirmed by pharmacologic inhibition of HIF-1alpha and by expression of a
      dominant-negative HIF mutant. Overexpression of HIF-1alpha showed a time delay in
      HIF-1beta induction, thus arguing for HIF-1beta de novo synthesis rather than
      protein stabilization by heterodimerization. A Hen's egg test-chorioallantoic
      membrane model of angiogenesis and invasion indicated a local expression of HIF
      1beta and implies a biological relevance of these findings. In summary, this
      study demonstrates the HIF-1alpha-dependent regulation of HIF-1beta under hypoxic
      conditions for the first time. The results indicate a novel cell specific
      mechanism which might prevent HIF-1beta to become a limiting factor.

PMID- 23541583
TI  - TRESK potassium channel in human T lymphoblasts.
AB  - TRESK (TWIK-related spinal cord K(+)) channel, encoded by KCNK18 gene, belongs to
      the double-pore domain K(+) channel family and in normal conditions is expressed
      predominantly in the central nervous system. In our previous patch-clamp study on
      Jurkat T lymphoblasts we have characterized highly selective K(+) channel with
      pharmacological profile identical to TRESK. In the present work, the presence of
      KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but
      not in resting peripheral blood lymphocytes of healthy donors. Positive
      immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in
      germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute
      lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane,
      intracellular TRESK localization was also revealed. Possible involvement of TRESK
      channel in lymphocyte proliferation and tumorigenesis is discussed.

PMID- 23541584
TI  - Partially acetylated chitooligosaccharides bind to YKL-40 and stimulate growth of
      human osteoarthritic chondrocytes.
AB  - Recent evidences indicating that cellular kinase signaling cascades are triggered
      by oligomers of N-acetylglucosamine (ChOS) and that condrocytes of human
      osteoarthritic cartilage secrete the inflammation associated chitolectin YKL-40,
      prompted us to study the binding affinity of partially acetylated ChOS to YKL-40
      and their effect on primary chondrocytes in culture. Extensive chitinase
      digestion and filtration of partially deacetylated chitin yielded a mixture of
      ChOS (OligominTM) and further ultrafiltration produced T-ChOSTM, with
      substantially smaller fraction of the smallest sugars. YKL-40 binding affinity
      was determined for the different sized homologues, revealing micromolar
      affinities of the larger homologues to YKL-40. The response of osteoarthritic
      chondrocytes to OligominTM and T-ChOSTM was determined, revealing 2- to 3-fold
      increases in cell number. About 500 MUg/ml was needed for OligominTM and around
      five times lower concentration for T-ChOSTM, higher concentrations abolished this
      effect for both products. Addition of chitotriose inhibited cellular responses
      mediated by larger oligosaccharides. These results, and the fact that the
      partially acetylated T-ChOSTM homologues should resist hydrolysis, point towards
      a new therapeutic concept for treating inflammatory joint diseases.

PMID- 23541586
TI  - Positive contribution of IRE1alpha-XBP1 pathway to the expression of placental
      cathepsins.
AB  - IRE1alpha is an ER-located transmembrane RNase whose activation leads to the
      production of the transcriptional factor, XBP1. Recently, many studies report
      that IRE1alpha-XBP1 pathway has novel and significant roles in placenta. However,
      its molecular details have been still unknown. To address this point, we have
      focused on the molecular linkage between IRE1alpha-XBP1 pathway and Cts7 and
      Cts8, which are essential cathepsins for placenta formation. In cellular model,
      this pathway positively contributed to their expression at transcriptional level.
      In addition, the disruption of IRE1alpha or XBP1 in animal model significantly
      attenuated their transcripts in placenta. These results indicated that IRE1alpha
      XBP1 pathway function as a specific program supporting the placenta formation by
      ensuring the moderate expression of specific subset of placental cathepsins.

PMID- 23541585
TI  - Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein,
      affects histone H3 phosphorylation and corresponds to proliferation of cancer and
      smooth muscle cells.
AB  - CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17kDa) is a
      cytoplasmic protein predominantly expressed in mature smooth muscle (SM) that
      regulates the myosin-associated PP1 holoenzyme (MLCP). Here, we show CPI-17
      expression in proliferating cells, such as pancreatic cancer and hyperplastic SM
      cells. Immunofluorescence showed that CPI-17 was concentrated in nuclei of human
      pancreatic cancer (Panc1) cells. Nuclear accumulation of CPI-17 was also detected
      in the proliferating vascular SM cell culture and cells at neointima of rat
      vascular injury model. The N-terminal 21-residue tail domain of CPI-17 was
      necessary for the nuclear localization. Phospho-mimetic Asp-substitution of CPI
      17 at Ser12 attenuated the nuclear import. CPI-17 phosphorylated at Ser12 was not
      localized at nuclei, suggesting a suppressive role of Ser12 phosphorylation in
      the nuclear import. Activated CPI-17 bound to all three isoforms of PP1 catalytic
      subunit in Panc1 nuclear extracts. CPI-17 knockdown in Panc1 resulted in
      dephosphorylation of histone H3 at Thr3, Ser10 and Thr11, whereas it had no
      effects on the phosphorylation of myosin light chain and merlin, the known
      targets of MLCP. In parallel, CPI-17 knockdown suppressed Panc1 proliferation. We
      propose that CPI-17 accumulated in the nucleus through the N-terminal tail
      targets multiple PP1 signaling pathways regulating cell proliferation.

PMID- 23541587
TI  - A heteroallelic Drosophila insulin-like receptor mutant and its use in validating
      physiological activities of food constituents.
AB  - Here we report an additional Drosophila transheterozygote
      InR(GS15311)/InR(GS50346) carrying two different P-element-inducible alleles of
      insulin-like receptor gene (InR). InR(GS15311)/InR(GS50346) flies exhibit the
      following phenotypes previously reported in InR and insulin/IGF-1 signaling (IIS)
      pathway-related gene mutants: small bodies, developmental delay, shortened
      lifespan, and increased fasting resistance. All of these characteristics are
      shared among flies carrying mutated genes implicated in the pathway. This
      heteroallelic combination exhibited fertility but resulted in male semilethality,
      while females were viable and grew into adults. Furthermore, an experimental
      model employing the InR(GS15311)/InR(GS50346) strain confirmed negligible
      involvement of royal jelly in IIS. Thus, the heteroallelic InR mutant, discovered
      in this study, will serve as a good model for multiple purposes: investigating
      the IIS mechanisms; identifying and validating the ingredients that prevent type
      II diabetes; and screening of food constituents associated with IIS.

PMID- 23541588
TI  - Structural basis for cell-cycle-dependent nuclear import mediated by the
      karyopherin Kap121p.
AB  - Kap121p (also known as Pse1p) is an essential karyopherin that mediates nuclear
      import of a plethora of cargoes including cell cycle regulators, transcription
      factors, and ribosomal proteins in Saccharomyces cerevisiae. It has been proposed
      that the spindle assembly checkpoint signaling triggers molecular rearrangements
      of nuclear pore complexes and thereby arrests Kap121p-mediated nuclear import at
      metaphase, while leaving import mediated by other karyopherins unaffected. The
      Kap121p-specific import inhibition is required for normal progression through
      mitosis. To understand the structural basis for Kap121p-mediated nuclear import
      and its unique regulatory mechanism during mitosis, we determined crystal
      structures of Kap121p in isolation and also in complex with either its import
      cargoes or nucleoporin Nup53p or RanGTP. Kap121p has a superhelical structure
      composed of 24 HEAT repeats. The structures of Kap121p-cargo complexes define a
      non-conventional nuclear localization signal (NLS) that has a consensus sequence
      of KV/IxKx1-2K/H/R. The structure of Kap121p-Nup53p complex shows that cargo and
      Nup53p compete for the same high-affinity binding site, explaining how Nup53p
      binding forces cargo release when the Kap121p-binding site of Nup53p is exposed
      during mitosis. Comparison of the NLS and RanGTP complexes reveals that RanGTP
      binding not only occludes the cargo-binding site but also forces Kap121p into a
      conformation that is incompatible with NLS recognition.

PMID- 23541589
TI  - An ire1-phk1 chimera reveals a dispensable role of autokinase activity in
      endoplasmic reticulum stress response.
AB  - The endoplasmic reticulum transmembrane receptor Ire1 senses over-accumulation of
      unfolded proteins in the endoplasmic reticulum and initiates the unfolded protein
      response (UPR). The cytoplasmic portion of Ire1 has a protein kinase domain (KD)
      and a kinase extension nuclease (KEN) domain that cleaves an mRNA for encoding
      the Hac1 transcription factor needed to express UPR genes. During this UPR
      signaling, Ire1 proteins self-assemble into an oligomer of dimers, which
      essentially requires autophosphorylation of a constituent activation loop in the
      KD. However, it is not clear how dimerization, autophosphorylation, and KEN
      domain function are precisely coordinated. In this study, we uncoupled the KD and
      KEN domain functions, by removing the activation loop along with an extended
      region that we called the auto-inhibitory region (AIR), or by swapping the
      activation loop with a homologous loop from phosphorylase kinase 1 (Ire1(PHK)).
      Both Ire1(DeltaAIR) and Ire1(PHK) activated the UPR even when either protein
      contained a mutation (D797A) that abolished the ability of Ire1 KD to transfer
      phosphates to the AIR. Neither protein functioned when containing mutations in
      key ATP binding residues (E746A and N749A) or in residues that disrupted Ire1
      dimer interface (W426A or R697D). We interpret these results as evidence
      supporting the notion that the primary function of the kinase domain is to
      autophosphorylate the AIR in order to relieve auto-inhibition and that ADP acts
      as a switch to activate the KEN domain-catalyzed HAC1 mRNA cleavage.

PMID- 23541590
TI  - Nucleotide-dependent lateral and longitudinal interactions in microtubules.
AB  - Microtubule (MT) stability is related to the hydrolysis of the guanosine
      triphosphate nucleotide (NT) bound to beta-tubulin. However, the molecular
      mechanism by which the NT state influences the stability of the contacts in the
      MT lattice remains elusive. Here, we present large-scale atomistic simulations of
      different tubulin aggregates, including individual dimers, short protofilaments,
      a small lattice patch, and a piece of the MT lattice with two infinite
      protofilaments in both NT states. Together with a coarse-grained (CG) analysis of
      the fluctuations, these simulations highlight several regions of the protein
      where local changes are induced by the NT state or by the lateral and
      longitudinal contacts in the aggregates. Additionally, the CG analysis provides
      an indication of how the structural changes affect the bonds between the
      proteins. The results suggest a consistent picture of a possible molecular
      mechanism by which the NT state induces changes in the H1-S2 loop and more stable
      longitudinal bonds, both of which locate the H1-S2 and M-loop in more favorable
      positions to form lateral contacts.

PMID- 23541591
TI  - The mysterious C-terminal tail of alpha-synuclein: nanobody's guess.

PMID- 23541592
TI  - Quality control methods for optimal BCR-ABL1 clinical testing in human whole
      blood samples.
AB  - Reliable breakpoint cluster region (BCR)--Abelson (ABL) 1 measurement is
      essential for optimal management of chronic myelogenous leukemia. There is a need
      to optimize quality control, sensitivity, and reliability of methods used to
      measure a major molecular response and/or treatment failure. The effects of room
      temperature storage time, different primers, and RNA input in the reverse
      transcription (RT) reaction on BCR-ABL1 and beta-glucuronidase (GUSB) cDNA yield
      were assessed in whole blood samples mixed with K562 cells. BCR-ABL1 was measured
      relative to GUSB to control for sample loading, and each gene was measured
      relative to known numbers of respective internal standard molecules to control
      for variation in quality and quantity of reagents, thermal cycler conditions, and
      presence of PCR inhibitors. Clinical sample and reference material measurements
      with this test were concordant with results reported by other laboratories. BCR
      ABL1 per 10(3) GUSB values were significantly reduced (P = 0.004) after 48-hour
      storage. Gene-specific primers yielded more BCR-ABL1 cDNA than random hexamers at
      each RNA input. In addition, increasing RNA inhibited the RT reaction with random
      hexamers but not with gene-specific primers. Consequently, the yield of BCR-ABL1
      was higher with gene-specific RT primers at all RNA inputs tested, increasing to
      as much as 158-fold. We conclude that optimal measurement of BCR-ABL1 per 10(3)
      GUSB in whole blood is obtained when gene-specific primers are used in RT and
      samples are analyzed within 24 hours after blood collection.

PMID- 23541593
TI  - Novel method for PIK3CA mutation analysis: locked nucleic acid--PCR sequencing.
AB  - Somatic mutations in PIK3CA are commonly seen in invasive breast cancer and
      several other carcinomas, occurring in three hotspots: codons 542 and 545 of exon
      9 and in codon 1047 of exon 20. We designed a locked nucleic acid (LNA)-PCR
      sequencing assay to detect low levels of mutant PIK3CA DNA with attention to
      avoiding amplification of a pseudogene on chromosome 22 that has >95% homology to
      exon 9 of PIK3CA. We tested 60 FFPE breast DNA samples with known PIK3CA mutation
      status (48 cases had one or more PIK3CA mutations, and 12 were wild type) as
      identified by PCR-mass spectrometry. PIK3CA exons 9 and 20 were amplified in the
      presence or absence of LNA-oligonucleotides designed to bind to the wild-type
      sequences for codons 542, 545, and 1047, and partially suppress their
      amplification. LNA-PCR sequencing confirmed all 51 PIK3CA mutations; however, the
      mutation detection rate by standard Sanger sequencing was only 69% (35 of 51). Of
      the 12 PIK3CA wild-type cases, LNA-PCR sequencing detected three additional
      H1047R mutations in "normal" breast tissue and one E545K in usual ductal
      hyperplasia. Histopathological review of these three normal breast specimens
      showed columnar cell change in two (both with known H1047R mutations) and
      apocrine metaplasia in one. The novel LNA-PCR shows higher sensitivity than
      standard Sanger sequencing and did not amplify the known pseudogene.

PMID- 23541594
TI  - Out-of-body experience in the Karakorum.

PMID- 23541595
TI  - Consensus statement on Concussion in Sport--the 4th International Conference on
      Concussion in Sport held in Zurich, November 2012.

PMID- 23541596
TI  - Neurobiology of an endophenotype: modeling the progression of alcohol addiction
      in rodents.
AB  - Most adults in Western society consume alcohol on a regular basis with few or no
      negative consequences. However, for certain individuals, alcohol use escalates,
      leading to uncontrolled drinking bouts, craving, and repeated episodes of
      relapse. The transition from regulated to uncontrolled and compulsive drinking is
      a defining feature (i.e. an endophenotype) of alcohol addiction. This behavioral
      progression can be modeled in rodent paradigms that parallel the diagnostic
      criteria for addiction in humans. Using these criteria as a framework, this
      review outlines the neurobiological factors associated with increased
      vulnerability to excessive, compulsive, and dysregulated alcohol intake in
      rodents. We conclude by noting gaps in the literature and outline important
      directions for future research. 

PMID- 23541598
TI  - Hydroa vacciniforme-like cutaneous T-cell lymphoma: clinicopathologic and
      immunohistochemical study of 12 cases.
AB  - BACKGROUND: Hydroa vacciniforme (HV)-like lymphoma (HVL) is a rare and aggressive
      cutaneous T-cell lymphoma occurring mainly in children in Latin America and Asia.
      Chronic latent Epstein-Barr virus infection has been associated with both HV and
      HVL. OBJECTIVE: We sought to evaluate the clinical presentation and
      histopathology of this rare cutaneous T-cell lymphoma. METHODS: We reviewed the
      clinical, morphologic, and immunophenotypical features in 12 cases of HVL from
      Bolivia. RESULTS: All 12 patients had skin lesions in both sun-exposed and nonsun
      exposed areas, including edema, blistering, ulceration, and scarring, with a
      slowly progressive relapsing course. All 12 patients presented with systemic
      symptoms and showed a characteristic swelling of the nose and lips, and
      periorbital edema. Eight patients died an average of 5.3 months after initial
      diagnosis. Four patients remained alive with persistent disease. Histopathologic
      examination showed an atypical lymphocytic infiltrate with angiotropism and
      angiocentricity. The immunophenotype showed a cytotoxic T-cell (CD8(+)) profile.
      All cases were associated with Epstein-Barr virus infection and differed
      clinically from other forms of cutaneous T-cell lymphoma. LIMITATIONS: Only a
      limited number of cases were studied. CONCLUSIONS: This study confirms that HVL
      is a highly aggressive lymphoma, although some patients have a more indolent,
      chronic course.

PMID- 23541597
TI  - Neurobiology of gambling behaviors.
AB  - For many, gambling is a recreational activity that is performed periodically
      without ill effects, but for some, gambling may interfere with life functioning.
      A diagnostic entity, pathological gambling (PG), is currently used to define a
      condition marked by excessive and problematic gambling. In this review, the
      current status of understanding of the neurobiologies of gambling and PG is
      described. Multiple neurotransmitter systems (norepinephrine, serotonin,
      dopamine, opioid and glutamate) and brain regions (ventral striatum, ventromedial
      prefrontal cortex, insula, among others) have been implicated in gambling and PG.
      Considerations for future directions in gambling research, with a view towards
      translating neurobiological advances into more effective prevention and treatment
      strategies, are discussed. 

PMID- 23541599
TI  - Strain-induced crack formations in PDMS/DXA drug collars.
AB  - Drug-eluting systems are currently used in cardiac leads in order to reduce
      inflammation and fibrosis at the lead-tissue interface. Drug release from these
      drug delivery systems can be modulated by the manufacturing processes used to
      create the drug systems and assemble them onto the cardiac lead. In this study,
      scanning electron microscopy, atomic force microscopy and Raman microscopy are
      employed to explore the material characteristics of a polydimethylsiloxane
      dexamethasone acetate drug collar used on cardiac leads when varying the strain
      during collar assembly on the lead. A novel test fixture was created in order to
      investigate these drug collars under simulated stresses. Measurements of the
      collar while fitted to a rod revealed microcracks that are hypothesized to affect
      the drug release performance, resulting in increased drug elution. It was found
      that the strain that occurs during assembly of the collar onto the lead is a key
      factor in the formation of these microcracks. Results also suggest that cracks
      tend to form in areas of high drug particle density, and propagate between drug
      particles.

PMID- 23541600
TI  - Combining ageing and wear to assess the durability of zirconia-based ceramic
      heads for total hip arthroplasty.
AB  - The degradation of zirconia-based ceramic components for total hip arthroplasty
      (head and cup) has been the topic of many works. However, the correlation between
      what is measured in vivo and what is expected from in vitro simulations on hip
      simulators may be sometimes feeble, especially where zirconia component are
      concerned, mainly due to a lack of representativeness of in vitro experiments.
      The present study seeks to explore the combined effects of hydrothermal ageing
      and wear on zirconia components. It shows that hydrothermal ageing increases the
      roughness of zirconia components, which in turn might increase the wear rate of
      the polyethylene counterparts. Moreover, the friction during hip simulation
      increases the ageing rate of the zirconia components. This auto-accelerating
      degradation may explain some of the poor long-term in vivo results of zirconia
      hip prostheses reported in the literature. Finally, it is shown that zirconia
      toughened alumina components may be free from this combined degradation.

PMID- 23541601
TI  - Particle-size-dependent toxicity and immunogenic activity of mesoporous silica
      based adjuvants for tumor immunotherapy.
AB  - Conventionally used adjuvants alone are insufficient for triggering cell-mediated
      immunity, although they have been successfully developed to elicit protective
      antibody responses in some vaccines. Here, with the aim of eliciting cell
      mediated immunity, pathogen-associated molecular patterns (PAMPs) were
      immobilized with apatite within the pores and on the surface of mesoporous silica
      (MS) with particle sizes from 30 to 200nm to prepare novel MS-Ap-PAMP adjuvants,
      which showed cell-mediated anti-tumor immunity that was markedly improved
      compared to commercial alum adjuvant in vitro and in vivo. The toxicity and
      antitumor immunity of the MS-Ap-PAMP adjuvants were evaluated in vitro and in
      vivo. MS with a particle size of 200nm showed minimum in vitro cytotoxicity to
      NIH3T3 cells, particularly at concentrations no higher than 100MUgml(-1). In
      particular, apatite precipitation within the pores and on the surface of MS
      decreased the in vitro cytotoxicity of MS particles. The MS-Ap-PAMP adjuvants
      showed the maximum in vitro immunogenic activity among original culture medium,
      PAMP and alum-PAMP. Moreover, injection of the MS-Ap-PAMP adjuvant in combination
      with liquid-nitrogen-treated tumor tissue (derived from Lewis lung carcinoma
      cells) into C57BL/6 mice markedly inhibited in vivo tumor recurrence and the
      development of rechallenged tumor compared to those with commercial alum
      adjuvant. The MS-Ap-PAMP adjuvant contributed to the elicitation of a potent
      systemic antitumor immunity without obvious toxicity in vivo.

PMID- 23541602
TI  - Impact of benzyl butyl phthalate on shoaling behavior in Fundulus heteroclitus
      (mummichog) populations.
AB  - Fundulus heteroclitus preference for association with familiar conspecifics of
      similar body length was impacted by benzyl butyl phthalate (BBP); this was found
      to be a statically significant result with a p < 0.0001. When presented with
      equally sized shoals consisting of either large or small fish, the majority of
      unexposed (84%) and acetone exposed control (82%) fish selected the shoal of
      large fish. A small number of control fish chose either the shoal of small fish
      (6% and 10%) or the neutral zone (10% and 8%) where they were clear morphological
      outliers. Fish exposed to 0.1 mg/L BBP exposure daily for four weeks selected the
      shoal of small fish more often than unexposed or acetone controls (7.5- and 4.5
      fold respectively). They also remained in the neutral zone and displayed
      agitation at levels more than twice that of control. Agitation and shoal choice
      disruption are quantifiable behavioral responses that support the use of F.
      heteroclitus as a model for detecting sub-lethal BBP exposure.

PMID- 23541603
TI  - Trophic ecology of a resident Yellow-legged Gull (Larus michahellis) population
      in the Bay of Biscay.
AB  - Stable isotopes analyses (SIAs) are an efficient tool to obtain a general insight
      into the diet of generalist consumers, such as the Yellow-legged Gull (Larus
      michahellis). Here we analysed delta(13)C, delta(15)N and delta(34)S values in
      feathers of chicks and adults, and used Bayesian triple-isotope mixing models to
      reconstruct the diet of a Yellow-legged Gull population breeding in the
      southeastern Bay of Biscay. Questions to test were (1) whether adults and chicks
      rely on different feeding resources during breeding period; (2) whether there is
      a seasonal foraging effect involving a higher proportion of refuse food in winter
      compared to summer, and (3) the magnitude of the annual variation in diet. Prey
      consumption differed between colonies, among years, and also varied slightly
      between seasons, and this was mainly due to a differential use of prey of marine
      origin. However, diet did not differ between age classes. These results suggest a
      relatively monotonous diet with only slight variations from year to year,
      seasonally and at a local geographic scale.

PMID- 23541604
TI  - Improving noise resistance of intrinsic rhythms in a square-wave burster model.
AB  - The square-wave burster (Wang and Rinzel, 2003) is a class of autonomous bursting
      cells that share a bifurcation structure. It is known that this class of cells is
      involved in the generation of various life-supporting rhythms. In our research to
      realize an electronic circuit that mimics the rhythm generating mechanism in the
      square-wave burster, our circuit experimentally exhibited severe fluctuations in
      its rhythmic activity. We have found a noise-sensitive region in the phase
      portrait of the ideal model and have proposed modifications of the model that can
      reduce this fluctuation. A possible modification to ionic-conductance neuron
      models (Kohno and Aihara, 2011) was inspired by them. This modification, however,
      cannot be applied to a group of square-wave bursters, including the Butera-Rinzel
      Smith model (Butera et al., 1999; Del Negro et al., 2001), which is a model of
      the pre-Botzinger complex bursting neuron that plays a crucial role in the
      generation of respiration rhythms, because this modification premises that the
      slow dynamics originates from an activation gate variable of a hyperpolarizing
      ionic current. However, in some square-wave bursters, they are controlled by an
      inactivation gate variable of a depolarizing ionic current. In this study, we
      proposed a similar modification with a completely different mechanism that can be
      applied to this group of square-wave bursters. In the presence of noises, the
      modified Butera-Rinzel-Smith model can generate rhythmic activity that is more
      stable and similar to biological observations than the original model. The
      mechanisms underlying this modification are explained with noisy bifurcation
      diagrams.

PMID- 23541605
TI  - On evaluation of infection probabilities for different age groups.
AB  - It is well known that evaluation of parameters for any mathematical model is
      always very important and often a very difficult problem. This is especially true
      for agents-based models because as a rule the evaluation of an agent's parameters
      can be made only based on available information from the higher levels of a
      complex system. Such problems can be ill-posed or even have a non-unique
      solution. That is why there is no general algorithm for solving these problems
      and a researcher has to search for it for every specific model type. In this
      paper the problem of evaluating transmission probabilities for different age
      groups during an influenza epidemic/pandemic in a city will be considered. In
      order to solve this problem a regularization procedure based on illness attack
      rates for several age groups (cumulated numbers of infected residents as
      functions of time) is proposed and validated. It can be used for past epidemics
      to estimate the efficiency or inefficiency of undertaken interventions, to
      propose new ones and to reveal its advantages and shortcomings. Under some
      conditions it can be used to model the possible dynamics of a coming epidemic.

PMID- 23541606
TI  - Insights into the different functions of multiple peptidoglycan recognition
      proteins in the immune response against bacteria in the mosquito, Armigeres
      subalbatus.
AB  - Peptidoglycan recognition proteins (PGRPs) are a group of proteins that recognize
      and/or bind to peptidoglycan on the surface of a number of pathogens. To
      understand the roles of multiple PGRPs in the mosquito Armigeres subalbatus
      (AsPGRPs), we studied the effects of infection of two bacteria, the gram negative
      Escherichia coli and the gram positive Micrococcus luteus, on the transcriptional
      expression of AsPGRPs and RNA interference (RNAi) of AsPGRPs on the immune
      responses of mosquitoes against the two bacteria. Injection of E. coli or M.
      luteus into adult mosquitoes both significantly increased the transcription of
      AsPGRP-S1, but not the other AsPGRPs. A mosquito survival assay using injection
      of E. coli or M. luteus into AsPGRP double-stranded RNA (dsRNA) injected
      mosquitoes showed that RNAi of AsPGRPs had different impacts on the survival
      abilities of mosquitoes, and that AsPGRP-LCs seem to be the most critical ones.
      Real-time Polymerase Chain Reaction (real-time PCR) analysis indicated that the
      expression of four antimicrobial peptides (AMPs) was dramatically changed after
      AsPGRP-LB and AsPGRP-LC RNAi, although AsPGRP-S1 and AsPGRP-LE had slight, but
      significant, effects, suggesting that the changes in survival abilities were
      potentially due to the changes in AMP expression after AsPGRP RNAi. In addition,
      bacterial challenges following AsPGRP-LC RNAi did not induce the expression of
      AMPs to their normal level as in control experiments. An in vivo assay indicated
      that AsPGRP-LC RNAi had no significant effects on the phagocytic ability of the
      hemocytes, suggesting that AsPGRP-LC is not a key factor mediating phagocytosis
      of bacteria in this mosquito.

PMID- 23541607
TI  - The insulin/TOR signal transduction pathway is involved in the nutritional
      regulation of juvenile hormone synthesis in Aedes aegypti.
AB  - Juvenile hormone (JH) levels must be modulated to permit the normal progress of
      development and reproductive maturation in mosquitoes. JH is part of a
      transduction system that assesses nutritional information and controls
      reproduction in mosquitoes. Adult female Aedes aegypti show nutritionally
      dependent dynamic changes in corpora allata (CA) JH biosynthetic activities. A
      coordinated expression of most JH biosynthetic enzymes has been described in
      female pupae and adult mosquitoes; increases or decreases in transcript levels
      for all the enzymes were concurrent with increases or decreases in JH synthesis;
      suggesting that transcriptional changes are at least partially responsible for
      the dynamic changes of JH biosynthesis. The goal of the present study is to
      identify signaling network components responsible for the nutritional-dependent
      changes of JH synthesis in the CA of mosquitoes. The insulin/TOR signaling
      network plays a central role in the transduction of nutritional signals that
      regulate cell growth and metabolism in insects. These pathways have also been
      suggested as a link between nutritional signals and JH synthesis regulation in
      the CA of cockroaches and flies. We used a combination of in vitro studies and in
      vivo genetic knockdown experiments to explore nutritional signaling pathways in
      the CA. Our results suggest that the insulin/TOR pathway plays a role in the
      transduction of the nutritional information that regulates JH synthesis in
      mosquitoes. Transcriptional regulation of the genes encoding JH biosynthetic
      enzymes is at least partially responsible for these nutritionally modulated
      changes of JH biosynthesis.

PMID- 23541608
TI  - Modelling Coronary Heart Disease Mortality declines in the Republic of Ireland,
      1985-2006.
AB  - BACKGROUND: Consistent declines in coronary heart disease (CHD) death rates have
      been previously observed in Ireland since 1985. AIMS & METHODS: To use the
      previously validated Irish IMPACT CHD mortality model to further examine the
      subsequent CHD mortality falls from 1985 through to 2006, and to determine the
      contribution of risk factor changes and "evidence based" treatments to this
      decline by age and gender. RESULTS: CHD mortality rates fell by 68% in men (63%
      in 65-84 years) and by 69% in women (66% in 65-84 years). This resulted in
      approximately 6450 fewer CHD deaths than if mortality rates had not changed.
      Overall, approximately 40% (38% in men; 45% in women) of the CHD mortality
      decline could be attributed to improvements in treatment uptake, particularly
      secondary prevention (12%), angina (9%), and heart failure therapies (8%).
      Approximately 48% of the CHD mortality decline was attributable to risk factor
      improvements (54% in men; 37% in women); the biggest contributions came from
      falls in population systolic pressure (28%), cholesterol (24%), and physical
      inactivity levels (10%). Negative trends in diabetes and obesity levels generated
      an estimated 17% additional CHD deaths. The largest benefits from improvements in
      risk factors were seen in men aged 25-64 years, while the greatest treatment
      benefits occurred in women aged 65-84 years. The model explained approximately
      88% of the observed mortality declines. CONCLUSION: Falls in CHD mortality have
      continued in both sexes in Ireland, but with notable gender and age differences.
      The continued increase in diabetes and obesity levels is particularly worrying.

PMID- 23541609
TI  - Triptolide protects rat heart against pressure overload-induced cardiac fibrosis.
AB  - BACKGROUND: Emerging evidence underlines the role of inflammation activation in
      the process of cardiac fibrosis. Triptolide has potent anti-inflammatory and anti
      proliferative properties, and extensively used in the treatment of chronic
      inflammatory disorders. In the current study, we test the hypothesis that
      triptolide treatment facilitates to attenuate chronic pressure overload-induced
      cardiac fibrosis in a model of rat. METHODS: Adult male Sprague-Dawley rats were
      subjected to a suprarenal abdominal aorta constriction (AC) or sham (as control)
      to induce sustained pressure overload. Eight weeks later, rats were randomly
      assigned to receive triptolide (9 MUg/kg.d, i.p) or vehicle (0.1% dimethyl
      sulfoxide, 0.2 ml/d, i.p) treatment for an additional 8 weeks. RESULTS: AC caused
      significant pathological hypertrophy, cardiac fibrosis and reduced cardiac
      diastolic function. Triptolide treatment markedly inhibited AC-induced increases
      in myocardial collagen volume fraction, collagen type I/III deposition, left
      ventricular end-diastolic pressure, expressions of pro-fibrogenic factors
      (transforming growth factor-beta and angiotensin II) and pro-inflammatory
      cytokines (IL-1beta and IL-6), NF-kappaB activation and inflammatory cell
      infiltration in left ventricles compared with vehicle, without affecting cardiac
      hypertrophy. However, triptolide had no effects on systemic blood pressure and
      circulating angiotensin II level. CONCLUSIONS: Collectively, the findings
      suggested that triptolide treatment elicits favorable anti-fibrogenic effect in a
      blood pressure-independent manner, at least in part, through inhibiting
      myocardial pro-fibrogenic factor production and inflammatory activation in the
      pressure overloaded heart.

PMID- 23541610
TI  - Myocardial fibrosis in the right ventricle detected on ECG gated 320 slice CT
      showed a short term poor prognosis in subjects with pulmonary hypertension.

PMID- 23541611
TI  - Substrates of atrial arrhythmias: histological insights from patients with
      congenital heart disease.
AB  - BACKGROUND: The impact of overload duration and age on remodelling process in
      human atria remains controversial. We analysed histological markers of right
      atrial (RA) remodelling in CHD patients in order to provide some insights into
      impacts of age and overload duration on substrates of atrial arrhythmias.
      METHODS: Sixty-five CHD patients who underwent initial cardiac surgery were
      enrolled (median age 18 years). Patients with dominant left atrial overload were
      excluded. RA tissues resected from CHD patients during surgery were examined by
      means of histology and immunohistochemistry and compared with RA tissues from age
      matched control hearts from post-mortem (n=22, median age 22 years). Patient
      histories of preoperative SVTs and echocardiography were also examined. RESULTS:
      The greatest extent of fibrosis, the largest myocyte diameter and the longest
      capillary distance and the most CD45-positive cell infiltration was observed in
      CHD samples with SVT, followed by CHD without SVT and then control samples. All
      histological changes were correlated with age in CHD samples (r=0.462, 0.718,
      0.529 and 0.447, respectively) with relatively steep and continuous manner,
      whereas only myocyte diameter was correlated with age in control samples
      (r=0.576). RA dimensions and area obtained from echocardiography also correlated
      with histological markers in CHD patients. CONCLUSIONS: Dominant and chronic RA
      overload due to CHD resulted in time-course related RA structural remodelling,
      which could provide the background for atrial arrhythmia. The overload duration,
      rather than age, seems to be a key factor for atrial histological degeneration in
      the cohort of CHD.

PMID- 23541613
TI  - Surgical treatment for posterior ankle impingement.
AB  - PURPOSE: This study aims to provide an overview of both the open and endoscopic
      procedures used to treat posterior ankle impingement, as well as an analysis,
      evaluation, and comparison of their outcomes. METHODS: A systematic literature
      search of the Medline, Embase (Classic), and CINAHL (Cumulative Index to Nursing
      and Allied Health Literature) databases and the Cochrane Database of Clinical and
      Randomized Controlled Trials was performed. Quality of included studies was
      assessed by use of the Downs and Black scale. RESULTS: After we reviewed 783
      studies, 16 trials met the inclusion criteria. Of these trials, 6 reported on
      open surgical techniques and 10 evaluated endoscopic techniques. The complication
      rate (15.9% v 7.2%) and time to return to full activity (16.0 weeks v 11.3 weeks)
      differed between the 2 groups, both favoring endoscopic surgery. CONCLUSIONS:
      Although the level of evidence of the included studies is relatively low, it can
      be concluded that the endoscopic technique is superior to the open procedure.
      LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

PMID- 23541612
TI  - Using non-invasive methods to characterize gonadal hormonal patterns of southern
      three-banded armadillos (Tolypeutes matacus) housed in North American zoos.
AB  - Understanding the basic reproductive biology and limitations to successful
      breeding of the southern three-banded armadillo (Tolypeutes matacus) is necessary
      to maintain viable zoo populations. Our objectives were to: 1) describe the
      reproductive biology using non-invasive, fecal hormone analysis; 2) assess
      influence of season on gonadal hormonal patterns in both the sexes; 3)
      characterize reproductive cyclicity and pregnancy in the female; and 4)
      characterize the onset of sexual maturity in males. Nineteen armadillos were
      monitored including: 13 (7 males, 6 females) from Lincoln Park Zoo and six (3
      males, 3 females) from San Antonio Zoological Garden. Fecal samples (n=5220;
      275/animal/yr) were collected 5 to 7 times a week for 1 year. Hormones were
      extracted from feces and analyzed for progestagen (females) and androgen (males)
      metabolite concentrations using enzyme immunoassays. Mean estrous cycle length
      (26.4+/-1.3 days) did not vary (P<0.05) among individuals (n=9). Mean gestation
      length (n=3) was 114.0+/-0.6 days long with mean fecal progestagen metabolites
      increasing 10-fold during pregnancy. Seasons did not influence (P<0.05) fecal
      androgen or progestagen metabolites. These data can assist with management
      decisions, which will directly affect the success of this species in zoos.

PMID- 23541614
TI  - Bat Mx1 and Oas1, but not Pkr are highly induced by bat interferon and viral
      infection.
AB  - Bats harbour many emerging and re-emerging viruses, several of which are highly
      pathogenic in other mammals but cause no diseases in bats. As the interferon
      (IFN) response represents a first line of defence against viral infection, the
      ability of bats to control viral replication may be linked to the activation of
      the IFN system. The three most studied antiviral IFN-stimulated genes (ISGs) in
      other mammals; Pkr, Mx1 and Oas1 were examined in our model bat species, Pteropus
      alecto. Our results demonstrate that the three ISGs from P. alecto are highly
      conserved in their functional domains and promoter elements compared to
      corresponding genes from other mammals. However, P. alecto Oas1 contains two IFN
      stimulated response elements (ISRE) in its promoter region compared with the
      single ISRE present in human OAS1 which may lead to higher IFN inducibility of
      the bat gene. Both Oas1 and Mx1 were induced in a highly IFN-dependent manner
      following stimulation with IFN or synthetic double-strand RNA (dsRNA) whereas Pkr
      showed evidence of being induced in an IFN-independent manner. Furthermore, bat
      Oas1 appeared to be the most inducible of the three ISGs following either IFN
      stimulation or viral infection, providing evidence that Oas1 may play a more
      important role in antiviral activity in bats compared with Mx1 or Pkr. Our
      results have important implications for the different roles of ISGs in bats and
      provide the first step in understanding the role of these molecules in the
      ability of bats to coexist with viruses.

PMID- 23541615
TI  - Relative performances of artificial neural network and regression mapping tools
      in evaluation of spinal loads and muscle forces during static lifting.
AB  - Two artificial neural networks (ANNs) are constructed, trained, and tested to map
      inputs of a complex trunk finite element (FE) model to its outputs for spinal
      loads and muscle forces. Five input variables (thorax flexion angle, load
      magnitude, its anterior and lateral positions, load handling technique, i.e., one
      or two-handed static lifting) and four model outputs (L4-L5 and L5-S1 disc
      compression and anterior-posterior shear forces) for spinal loads and 76 model
      outputs (forces in individual trunk muscles) are considered. Moreover, full
      quadratic regression equations mapping input-outputs of the model developed here
      for muscle forces and previously for spine loads are used to compare the relative
      accuracy of these two mapping tools (ANN and regression equations). Results
      indicate that the ANNs are more accurate in mapping input-output relationships of
      the FE model (RMSE= 20.7 N for spinal loads and RMSE= 4.7 N for muscle forces) as
      compared to regression equations (RMSE= 120.4 N for spinal loads and RMSE=43.2 N
      for muscle forces). Quadratic regression equations map up to second order
      variations of outputs with inputs while ANNs capture higher order variations too.
      Despite satisfactory achievement in estimating overall muscle forces by the ANN,
      some inadequacies are noted including assigning force to antagonistic muscles
      with no activity in the optimization algorithm of the FE model or predicting
      slightly different forces in bilateral pair muscles in symmetric lifting
      activities. Using these user-friendly tools spine loads and trunk muscle forces
      during symmetric and asymmetric static lifts can be easily estimated.

PMID- 23541616
TI  - Effect of chronic intermittent hypoxia on leptin and leptin receptor protein
      expression in the carotid body.
AB  - This study was done to investigate whether chronic intermittent hypoxia (CIH)
      induced changes in leptin and leptin receptor protein levels, and known
      downstream mediators of leptin receptor signaling in the carotid body. Rats were
      subjected to CIH (120s normoxia, 80s hypoxia) or normoxia for 8h/day to either
      short term (7 days) or long term CIH exposure (95 days). After both 7 and 95 days
      of CIH, carotid body leptin protein expression was decreased, while protein
      levels of the long form leptin receptor (OB-Rb) were elevated. On the other hand,
      protein expression levels of the short form leptin receptor (OB-R100) were
      unchanged. Furthermore, phosphorylated signal transducer and activator of
      transcription 3 (pSTAT3) protein levels were found to be significantly decreased
      at only the 7 day period. On the other hand, suppressor of cytokine signaling 3
      (SOCS3) protein levels were elevated at only the 7 day period, while
      phosphorylated extracellular-signal-regulated kinase 1/2 (pERK1/2) was elevated
      only at the 95 day period. In both the normoxia and the CIH groups, carotid body
      leptin was decreased at the 95 day period compared to 7 days. However, OB-Rb or
      Ob-R100 protein levels were not changed in the normoxic or CIH group at either
      time point. Furthermore, pSTAT3 protein levels were found to be significantly
      higher, while SOCS3 levels were significantly lower in the 95 day CIH group
      compared to the 7 day CIH group. Taken together, these data indicate that CIH
      induces changes in leptin and leptin downstream signaling proteins within the
      carotid bodies which may contribute to alterations in carotid chemoreceptor
      sensitivity.

PMID- 23541617
TI  - Soluble amyloid precursor protein alpha and beta in CSF in Alzheimer's disease.
AB  - OBJECTIVE: Cerebral accumulation of amyloid beta (Abeta) is a pathological
      hallmark of Alzheimer's disease (AD). Proteolytic processing of amyloid precursor
      protein (APP) by alpha- or beta-secretase results in two soluble metabolites,
      sAPPalpha and sAPPbeta, respectively. However, previous data have shown that both
      alpha- and beta-secretase have multiple cleavage sites. The aim of this study was
      to characterize the C-termini of sAPPalpha and sAPPbeta in cerebrospinal fluid
      (CSF) by mass spectrometry (MS) and to evaluate whether different combinations of
      these fragments better separate between AD patients and controls by comparing two
      different sAPP immunoassays. METHODS: Using immunoprecipitation and high
      resolution MS, the APP species present in CSF were investigated. CSF levels of
      sAPPalpha and sAPPbeta from patients with AD (n=43) and from non-demented
      controls (n=44) were measured using AlphaLISA and MSD immunoassays that employ
      different antibodies for C-terminal recognition of sAPPalpha. RESULTS: Four
      different C-terminal forms of sAPP were identified, sAPPbeta-M671, sAPPbeta-Y681,
      sAPPalpha-Q686, and sAPPalpha-K687 (APP770 numbering). Neither immunoassay for
      the sAPP species could separate the two patient groups. The correlation (R(2))
      between the two immunoassays was 0.41 for sAPPalpha and 0.45 for sAPPbeta.
      CONCLUSION: Using high resolution MS, we show here for the first time that
      sAPPalpha in CSF ends at Q686 and K687. The findings also support the conclusion
      from several previous studies that sAPPalpha and sAPPbeta levels are unaltered in
      AD.

PMID- 23541618
TI  - Dopaminergic transmission in the midbrain ventral tegmental area in the induction
      of hippocampal theta rhythm.
AB  - Hippocampal rhythmic slow activity (RSA, theta) is regulated by many brainstem
      structures, including the midbrain ventral tegmental area (VTA). This work aimed
      at assessing the role of the dopaminergic (DA) transmission of the VTA in this
      regulation. Male Wistar rats (n=35) in urethane anaesthesia received an intra-VTA
      microinjection of either flupenthixol (FLU; doses of 5.0, 2.5, 1.25 and 0.625
      MUg) or amphetamine (AMPH; 2.5 and 5.0 MUg) following control solvent
      microinjection. Peak power (Pmax) and corresponding peak frequency (Fmax) for
      delta and theta bands were extracted from EEG recording. Flupenthixol at a dose
      of 1.25 MUg evoked long-lasting theta, continuing for 32.0 min on average, with a
      mean latency of 7.1 min. Other doses of FLU caused an increase of Pmax theta and
      reduction of Pmax delta without generating visually recognizable, regular theta
      rhythm. 5 MUg of AMPH evoked theta continuing for 24.4 min on average, with a
      mean latency of 9.7 min. The lower dose was much less effective, with its outcome
      resembling the one after the less active FLU doses. During pharmacologically
      induced theta rhythm, both after FLU and AMPH, brief episodes of asynchronous
      activity appeared periodically, and they were more frequent and longer in AMPH
      groups. AMPH may act locally on multiple sites, inhibiting DA cells in
      somatodendritic region but also increasing dopamine release in target structures,
      and this, depending on AMPH dose, can lead to induction of theta rhythm. Locally
      administered DA antagonist on the other hand, when used at a proper dose, can
      produce theta most likely by the mechanism of inhibiting autoreceptors.

PMID- 23541619
TI  - The role of CD200-CD200R in tumor immune evasion.
AB  - CD200 is a cell membrane protein that interacts with CD200 receptor (CD200R) of
      myeloid lineage cells. During tumor initiation and progression, CD200-positive
      tumor cells can interact with M1 and M2 macrophages through CD200-CD200R-compex,
      and downregulate IL-10 and IL-12 productions secreted primarily by M2 and M1
      macrophages, respectively. In the tumor microenvironment, IL-10 inhibits the
      activation of cytotoxic T lymphocytes (CTL), while IL-12 enhances CTL activation.
      In this paper, we used a system approach to determine the combined effect of
      CD200-CD200R interaction on tumor proliferation by developing a mathematical
      model. We demonstrate that blocking CD200 on tumor cells may have opposite
      effects on tumor proliferation depending on the "affinity" of the macrophages to
      form the CD200-CD200R-complex with tumor cells. Our results help understanding
      the complexities of tumor microenvironment.

PMID- 23541620
TI  - Sequence and structure space model of protein divergence driven by point
      mutations.
AB  - New folds of protein structures emerge in evolution as a result of insertions,
      deletions or shuffling of fragments of underlying gene sequences, and from
      aggregated effects of point mutations. The result of these evolutionary processes
      is a rich and complex universe of protein sequences and structures, with
      characteristic features such as heavy-tailed distribution of fold occurrences,
      and a distinct shape of relationship between sequence identity and structure
      similarity. Better understanding of how the protein universe evolved to its
      present form can be achieved by creating models of protein structure evolution.
      Here we introduce a stochastic model of evolution that involves residue
      substitutions as the sole source of structure innovation, and is nonetheless able
      to reproduce the diversity of the protein domains repertoire, its cluster
      structure with heavy-tailed distribution of family sizes, and presence of the
      twilight zone populated with remote homologs.

PMID- 23541621
TI  - Development and preclinical evaluation of safety and immunogenicity of an oral
      ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization
      factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen,
      administered alone and together with dmLT adjuvant.
AB  - A first-generation oral inactivated whole-cell enterotoxigenic Escherichia coli
      (ETEC) vaccine, comprising formalin-killed ETEC bacteria expressing different
      colonization factor (CF) antigens combined with cholera toxin B subunit (CTB),
      when tested in phase III studies did not significantly reduce overall (generally
      mild) ETEC diarrhea in travelers or children although it reduced more severe ETEC
      diarrhea in travelers by almost 80%. We have now developed a novel more
      immunogenic ETEC vaccine based on recombinant non-toxigenic E. coli strains
      engineered to express increased amounts of CF antigens, including CS6 as well as
      an ETEC-based B subunit protein (LCTBA), and the optional combination with a
      nontoxic double-mutant heat-labile toxin (LT) molecule (dmLT) as an adjuvant. Two
      test vaccines were prepared under GMP: (1) A prototype E. coli CFA/I-only
      formalin-killed whole-cell+LCTBA vaccine, and (2) A "complete" inactivated
      multivalent ETEC-CF (CFA/I, CS3, CS5 and CS6 antigens) whole-cell+LCTBA vaccine.
      These vaccines, when given intragastrically alone or together with dmLT in mice,
      were well tolerated and induced strong intestinal-mucosal IgA antibody responses
      as well as serum IgG and IgA responses to each of the vaccine CF antigens as well
      as to LT B subunit (LTB). Both mucosal and serum responses were further enhanced
      (adjuvanted) when the vaccines were co-administered with dmLT. We conclude that
      the new multivalent oral ETEC vaccine, both alone and especially in combination
      with the dmLT adjuvant, shows great promise for further testing in humans.

PMID- 23541622
TI  - Pneumococcal Surface Protein A does not affect the immune responses to a combined
      diphtheria tetanus and pertussis vaccine in mice.
AB  - The Pneumococcal Surface Protein A (PspA) is a promising candidate for the
      composition of a protein vaccine against Streptococcus pneumoniae. We have
      previously shown that the whole cell Bordetella pertussis vaccine (wP) is a good
      adjuvant to PspA, inducing protective responses against pneumococcal infection in
      mice. In Brazil, wP is administered to children, formulated with diphtheria and
      tetanus toxoids (DTPw) and aluminum hydroxide (alum) as adjuvant. A single
      subcutaneous dose of PspA5-DTPlow (a formulation containing PspA from clade 5 and
      a new generation DTPw, containing low levels of B. pertussis LPS and Alum)
      induced high levels of systemic anti-PspA5 antibodies in mice and conferred
      protection against respiratory lethal challenges with two different pneumococcal
      strains. Here we evaluate the mucosal immune responses against PspA5 as well as
      the immune responses against the DTP antigens in mice vaccinated with PspA5
      DTPlow. Subcutaneous immunization of mice with PspA5-DTPlow induced high levels
      of anti-PspA5 IgG in the airways but no IgA. In addition, no differences in the
      influx of cells to the respiratory mucosa, after the challenge, were observed in
      vaccinated mice, when compared with control mice. The levels of circulating anti
      pertussis, -tetanus and -diphtheria antibodies were equivalent in mice vaccinated
      with DTPlow or PspA5-DTPlow. Antibodies induced by DTPlow or PspA5-DTPlow showed
      similar ability to neutralize the cytotoxic effects of the diphtheria toxin on
      Vero cells. Furthermore, combination with PspA5 did not affect protection against
      B. pertussis and tetanus toxin challenges in mice. Our results support the
      proposal for a combined PspA-DTP vaccine.

PMID- 23541623
TI  - A Phase I, randomized, open-label study to evaluate the safety and immunogenicity
      of an enterovirus 71 vaccine.
AB  - BACKGROUND: Large-scale outbreaks of enterovirus 71 (EV71) infections have
      occurred in Asia-Pacific regions. Severe complications include encephalitis and
      poliomyelitis-like paralysis, cardiopulmonary collapse, and death, necessitating
      an effective vaccine against EV71. METHODS: In this randomized Phase I study, we
      evaluated the safety and immunogenicity of an inactivated alum-adjuvanted EV71
      whole-virus vaccine produced on Vero cell cultures. Sixty healthy volunteers aged
      20-60 years received two doses of vaccine, administered 21 days apart. Each dose
      contained either 5 MUg of EV71 antigen with 150 MUg of adjuvant (Group A05) or 10
      MUg of EV71 antigen with 300 MUg of adjuvant (Group B10). Serologic analysis was
      performed at baseline, day 21, and day 42. RESULTS: There were no serious adverse
      events. Mild injection site pain and myalgia were the most common adverse events
      with either vaccine formulation. The immunogenicity data showed that 90% of
      vaccine recipients have a 4-fold or greater increase in neutralization antibody
      titers (NT) after the first dose, without a further increase in NT after the
      second dose. The seroconversion rates on day 21 and day 42 were 86.7% and 93.1%
      respectively, in Group A05, and 92.9% and 96.3%, respectively, in Group B10.
      Thus, 5 MUg and 10 MUg of the EV71 vaccine can induce a remarkable immune
      response in healthy adults after only the first vaccination. CONCLUSION: The 5
      MUg and 10 MUg adjuvanted EV71 vaccines are generally safe and immunogenic in
      healthy adults. (ClinicalTrials.gov number, NCT01268787).

PMID- 23541624
TI  - Saving culture from selection: comment on "An evolutionary framework for cultural
      change: selectionism versus communal exchange" by L. Gabora.

PMID- 23541625
TI  - A cross-sectional examination of the relationships between caregiver proximal
      soothing and infant pain over the first year of life.
AB  - Although previous research has examined the relationships between caregiver
      proximal soothing and infant pain, there is a paucity of work taking infant age
      into account, despite the steep developmental trajectory that occurs across the
      infancy period. Moreover, no studies have differentially examined the
      relationships between caregiver proximal soothing and initial infant pain
      reactivity and pain regulation. This study examined how much variance in pain
      reactivity and pain regulation was accounted for by caregiver proximal soothing
      at 4 routine immunizations (2, 4, 6, and 12 months) across the first year of
      life, controlling for preneedle distress. One latent growth model was replicated
      at each of the 4 infant ages, using a sample of 760 caregiver-infant dyads
      followed longitudinally. Controlling for preneedle infant distress, caregiver
      proximal soothing accounted for little to no variance in infant pain reactivity
      or regulation at all 4 ages. Preneedle distress and pain reactivity accounted for
      the largest amount of variance in pain regulation, with this increasing after 2
      months. It was concluded that within each immunization appointment across the
      first year of life, earlier infant pain behaviour is a stronger predictor of
      subsequent infant pain behaviour than caregiver proximal soothing. Given the
      longer-term benefits that have been demonstrated for proximal soothing during
      distressing contexts, caregivers are still encouraged to use proximal soothing
      during infant immunizations.

PMID- 23541626
TI  - The morbidity and mortality outcomes of indigenous Australian peoples after
      isolated coronary artery bypass graft surgery: the influence of geographic
      remoteness.
AB  - BACKGROUND: Though Indigenous Australian peoples reportedly have poorer survival
      outcome after cardiac surgery, few studies have jointly documented the experience
      of major morbidity, and considered the influence of patient geographic
      remoteness. METHODS: From January 1998 to September 2008, major morbidity events
      and survival were recorded for 2748 consecutive patients undergoing coronary
      artery bypass graft surgery. Morbidity and survival analyses adjusted for
      propensity deciles based on patient ethnicity and age, sex, left ventricular
      ejection fraction, recent myocardial infarction, tobacco smoking, diabetes, renal
      disease and history of stroke. Sensitivity analyses controlled for the patient
      accessibility/remoteness index of Australia (ARIA). RESULTS: The 297 Indigenous
      Australian patients (10.8% of total) had greater odds for total morbidity
      (adjusted odds ratio = 1.55; 95% confidence interval [CI] 1.04-2.30) and
      prolonged ventilation (adjusted odds ratio = 2.08; 95% confidence interval [CI]
      1.25-3.44) in analyses adjusted for propensity deciles and geographic remoteness.
      With a median follow-up of 7.5 years (interquartile range 5.2-10.2), Indigenous
      Australian patients were found to experience 30% greater mortality risk
      (unadjusted hazard ratio = 1.30; 95% CI: 1.03-1.64, p = 0.03). The effect size
      strengthened after adjustment for propensity score (adjusted hazard ratio = 1.49;
      95% CI: 1.13-1.96, p = .004). Adjustment for ARIA categorisation strengthened the
      effect size (adjusted HR = 1.54 (95% CI: 1.11-2.13, p = .009). CONCLUSION:
      Indigenous Australian peoples were at greater risk for prolonged ventilation and
      combined morbidity outcome, and experienced poorer survival in the longer term.
      Higher mortality risk among Indigenous Australians was evident even after
      controlling for remoteness and accessibility to services.

PMID- 23541627
TI  - Pathophysiology of atherosclerosis plaque progression.
AB  - Atherosclerotic plaque rupture with luminal thrombosis is the most common
      mechanism responsible for the majority of acute coronary syndromes and sudden
      coronary death. The precursor lesion of plaque rupture is thought to be a thin
      cap fibroatheroma (TCFA) or "vulnerable plaque". TCFA is characterised by a
      necrotic core with an overlying thin fibrous cap (<=65 MUm) that is infiltrated
      by macrophages and T-lymphocytes. Intraplaque haemorrhage is a major contributor
      to the enlargement of the necrotic core. Haemorrhage is thought to occur from
      leaky vasa vasorum that invades the intima from the adventitia as the intima
      enlarges. The early atherosclerotic plaque progression from pathologic intimal
      thickening (PIT) to a fibroatheroma is thought to be the result of macrophage
      infiltration. PIT is characterised by the presence of lipid pools which consist
      of proteoglycan with lipid insudation. The conversion of the lipid pool to a
      necrotic core is poorly understood but is thought to occur as a result of
      macrophage infiltration which releases matrix metalloproteinase (MMPs) along with
      macrophage apoptosis that leads to the formation of a acellular necrotic core.
      The fibroatheroma has a thick fibrous cap that begins to thin over time through
      macrophage MMP release and apoptotic death of smooth muscle cells converting the
      fibroatheroma into a TCFA. Other causes of thrombosis include plaque erosion
      which is less frequent than plaque rupture but is a common cause of thrombosis in
      young individuals especially women <50 years of age. The underlying lesion
      morphology in plaque erosion consists of PIT or a thick cap fibroatheroma.
      Calcified nodule is the least frequent cause of thrombosis, which occurs in older
      individuals with heavily calcified and tortious arteries.

PMID- 23541628
TI  - Use of risk assessment analysis by failure mode, effects, and criticality to
      reduce door-to-balloon time.
AB  - STUDY OBJECTIVE: The Centers for Medicare & Medicaid Services currently endorses
      a door-to-balloon time of 90 minutes or less for patients presenting to the
      emergency department (ED) with ST-segment elevation myocardial infarction. Recent
      evidence shows that a door-to-balloon time of 60 minutes significantly decreases
      inhospital mortality. We seek to use a proactive risk assessment method of
      failure mode, effects, and criticality analysis (FMECA) to evaluate door-to
      balloon time process, to investigate how each component failure may affect the
      performance of a system, and to evaluate the frequency and the potential severity
      of harm of each failure. METHODS: We conducted a 2-part study: FMECA of the door
      to-balloon time system and process of care, and evaluation of a single
      institution's door-to-balloon time operational data using a retrospective
      observational cohort design. A multidisciplinary group of FMECA participants
      described the door-to-balloon time process to then create a comprehensive map and
      table listing all process steps and identified process failures, including their
      frequency, consequence, and causes. Door-to-balloon time operational data were
      assessed by "on" versus "off" hours. RESULTS: Fifty-one failure points were
      identified across 4 door-to-balloon time phases. Of the 12 high-risk failures,
      58% occurred between ECG and catheterization laboratory activation. Total door-to
      balloon time during on hours had a median time of 55 minutes (95% confidence
      interval 46 to 60 minutes) compared with 77 minutes (95% confidence interval 68
      to 83 minutes) during off hours. CONCLUSION: The FMECA revealed clear areas of
      potential delay and vulnerability that can be addressed to decrease door-to
      balloon time from 90 to 60 minutes. FMECAs can provide a robust assessment of
      potential risks and can serve as the platform for significant process improvement
      and system redesign for door-to-balloon time.

PMID- 23541629
TI  - Centering the pendulum: the evolution of emergency medicine opioid prescribing
      guidelines.

PMID- 23541630
TI  - Examining renal impairment as a risk factor for acute coronary syndrome: a
      prospective observational study.
AB  - STUDY OBJECTIVE: This study seeks to examine whether the finding of an abnormal
      estimated glomerular filtration rate (eGFR) in the emergency department (ED) was
      associated with acute coronary syndrome in the population of patients presenting
      for investigation of chest pain. METHODS: We used prospectively collected data on
      adult patients presenting with suspected acute coronary syndrome to 2 EDs in
      Australia and New Zealand. Trained research nurses collected clinical data with a
      customized case report form. Creatinine measurements were taken on presentation,
      and the glomerular filtration rate ([GFR]; milliliters per minute per 1.73 m(2))
      was estimated with the chronic kidney disease epidemiologic collaboration
      equation. The primary endpoint was acute coronary syndrome within 30 days of
      presentation, as adjudicated by cardiologists using standardized guidelines.
      Logistic regression analyses examined the relationship between eGFR and acute
      coronary syndrome. RESULTS: Acute coronary syndrome was diagnosed in 421 (21%) of
      the 1,968 patients recruited. Compared with patients with an eGFR greater than 90
      mL/minute per 1.73 m(2), patients with an eGFR between 60 and 90 mL/minute per
      1.73 m(2) and patients with an eGFR less than 60 mL/minute per 1.73 m(2) were
      1.64 (95% confidence interval 1.10 to 2.44) and 1.70 (95% confidence interval
      1.01 to 2.77) times more likely to receive a diagnosis of acute coronary syndrome
      after controlling for age, sex, hypertension, dyslipidemia, family history of
      cardiac disease, diabetes, patient history of cardiac disease, cardiac troponin
      level, and ECG findings. CONCLUSION: There is an independent association between
      eGFR and acute coronary syndrome risk in patients presenting to the ED with chest
      pain; this association is independent of age, traditional cardiac risk factors,
      medical history, troponin level, and ECG findings. Reduced eGFR should be
      considered an acute coronary syndrome risk factor, and clinicians should maintain
      high clinical suspicion for acute coronary syndrome in patients with abnormal
      renal function results regardless of whether they have known kidney disease,
      traditional acute coronary syndrome risk factors, or abnormal diagnostic test
      results. Risk stratification tools should include reduced eGFR as a high-risk
      feature.

PMID- 23541631
TI  - Targeting miRNAs to treat Hepatitis C Virus infections and liver pathology:
      Inhibiting the virus and altering the host.
AB  - Hepatitis C Virus (HCV) infection-induced liver disease is a growing problem
      worldwide, and is the primary cause of liver failure requiring liver
      transplantation in North America. Improved therapeutic strategies are required to
      control and possibly eradicate HCV infections, and to modulate HCV-induced liver
      disease. Cellular microRNAs anneal to and regulate mRNA translation and stability
      and form a regulatory network that modulates virtually every cellular process.
      Thus, miRNAs are promising cellular targets for therapeutic intervention for an
      array of diseases including cancer, metabolic diseases, and virus infections. In
      this review we outline the features of miRNA regulation and how miRNAs may be
      targeted in strategies to modulate HCV replication and pathogenesis. In
      particular, we highlight miR-122, a miRNA that directly modulates the HCV life
      cycle using an unusual mechanism. This miRNA is very important since miR-122
      antagonists dramatically reduced HCV titres in HCV-infected chimpanzees and
      humans and currently represents the most likely candidate to be the first miRNA
      based therapy licensed for use. However, we also discuss other miRNAs that
      directly or indirectly alter HCV replication efficiency, liver cirrhosis,
      fibrosis and the development of hepatocellular carcinoma (HCC). We also discuss a
      few miRNAs that might be targets to treat HCV in cases of HCV/HIV co-infection.
      Finally, we review methods to deliver miRNA antagonists and mimics to the liver.
      In the future, it may be possible to design and deliver specific combinations of
      miRNA antagonists and mimics to cure HCV infection or to limit liver
      pathogenesis. 

PMID- 23541632
TI  - Shared and distinct intrinsic functional network centrality in autism and
      attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Individuals with autism spectrum disorders (ASD) often exhibit
      symptoms of attention-deficit/hyperactivity disorder (ADHD). Across both
      disorders, observations of distributed functional abnormalities suggest aberrant
      large-scale brain network connectivity. Yet, common and distinct network
      correlates of ASD and ADHD remain unidentified. Here, we aimed to examine
      patterns of dysconnection in school-age children with ASD and ADHD and typically
      developing children who completed a resting state functional magnetic resonance
      imaging scan. METHODS: We measured voxelwise network centrality, functional
      connectivity metrics indexing local (degree centrality [DC]) and global
      (eigenvector centrality) functional relationships across the entire brain
      connectome, in resting state functional magnetic resonance imaging data from 56
      children with ASD, 45 children with ADHD, and 50 typically developing children. A
      one-way analysis of covariance, with group as fixed factor (whole-brain
      corrected), was followed by post hoc pairwise comparisons. RESULTS: Cortical and
      subcortical areas exhibited centrality abnormalities, some common to both ADHD
      and ASD, such as in precuneus. Others were disorder-specific and included ADHD
      related increases in DC in right striatum/pallidum, in contrast with ASD-related
      increases in bilateral temporolimbic areas. Secondary analyses differentiating
      children with ASD into those with or without ADHD-like comorbidity (ASD(+) and
      ASD(-), respectively) revealed that the ASD(+) group shared ADHD-specific
      abnormalities in basal ganglia. By contrast, centrality increases in
      temporolimbic areas characterized children with ASD regardless of ADHD-like
      comorbidity. At the cluster level, eigenvector centrality group patterns were
      similar to DC. CONCLUSIONS: ADHD and ASD are neurodevelopmental disorders with
      distinct and overlapping clinical presentations. This work provides evidence for
      both shared and distinct underlying mechanisms at the large-scale network level.

PMID- 23541633
TI  - Cognitive impairment and dentate gyrus synaptic dysfunction in experimental
      parkinsonism.
AB  - BACKGROUND: Parkinson's disease (PD) is characterized by the progressive
      degeneration of the nigrostriatal dopaminergic pathway and the emergence of
      rigidity, tremor, and bradykinesia. Accumulating evidence indicates that PD is
      also accompanied by nonmotor symptoms including cognitive deficits, often
      manifested as impaired visuospatial memory. METHODS: We studied cognitive
      performance and synaptic plasticity in a mouse model of PD, characterized by
      partial lesion of the dopaminergic and noradrenergic inputs to striatum and
      hippocampus. Sham- and 6-hydroxydopamine-lesioned mice were subjected to the
      novel object recognition test, and long-term potentiation was examined in the
      dentate gyrus and CA1 regions of the hippocampus. RESULTS: Bilateral 6
      hydroxydopamine lesion reduced long-term but not short-term novel object
      recognition and decreased long-term potentiation specifically in the dentate
      gyrus. These abnormalities did not depend on the loss of noradrenaline but were
      abolished by the antiparkinsonian drug, L-DOPA, or by SKF81297, a dopamine D1
      type receptor agonist. In contrast, activation of dopamine D2-type receptors did
      not modify the effects produced by the lesion. Blockade of the extracellular
      signal-regulated kinases prevented the ability of SKF81297 to rescue novel object
      recognition and long-term potentiation. CONCLUSIONS: These findings show that
      partial dopamine depletion leads to impairment of long-term recognition memory
      accompanied by abnormal synaptic plasticity in the dentate gyrus. They also
      demonstrate that activation of dopamine D1 receptors corrects these deficits,
      through a mechanism that requires intact extracellular signal-regulated kinases
      signaling.

PMID- 23541634
TI  - Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory
      and anti-rheumatic effects.
AB  - Epigenetic modifications represent a promising new approach to modulate cell
      functions as observed in autoimmune diseases. Emerging evidence suggests the
      utility of HDAC inhibitors in the treatment of chronic immune and inflammatory
      disorders. However, class and isoform selective inhibition of HDAC is currently
      favored as it limits the toxicity that has been observed with pan-HDAC
      inhibitors. HDAC6, a member of the HDAC family, whose major substrate is alpha
      tubulin, is being increasingly implicated in the pathogenesis of inflammatory
      disorders. The present study was carried out to study the potential anti
      inflammatory and anti-rheumatic effects of HDAC6 selective inhibitor Tubastatin.
      Tubastatin, a potent human HDAC6 inhibitor with an IC50 of 11 nM showed
      significant inhibition of TNF-alpha and IL-6 in LPS stimulated human THP-1
      macrophages with an IC50 of 272 nM and 712 nM respectively. Additionally,
      Tubastatin inhibited nitric oxide (NO) secretion in murine Raw 264.7 macrophages
      dose dependently with an IC50 of 4.2 MUM and induced alpha-tubulin
      hyperacetylation corresponding to HDAC6 inhibition in THP-1 cells without
      affecting the cell viability. Tubastatin showed significant inhibition of paw
      volume at 30 mg/kg i.p. in a Freund's complete adjuvant (FCA) induced animal
      model of inflammation. The disease modifying activity of Tubastatin was also
      evident in collagen induced arthritis DBA1 mouse model at 30 mg/kg i.p. The
      significant attenuation of clinical scores (~70%) by Tubastatin was confirmed
      histopathologically and was found comparable to dexamethasone (~90% inhibition of
      clinical scores). Tubastatin showed significant inhibition of IL-6 in paw tissues
      of arthritic mice. The present work has demonstrated anti-inflammatory and
      antirheumatic effects of a selective HDAC6 inhibitor Tubastatin.

PMID- 23541635
TI  - Differential beta-arrestin2 requirements for constitutive and agonist-induced
      internalization of the CB1 cannabinoid receptor.
AB  - CB1 cannabinoid receptor (CB1R) undergoes both constitutive and agonist-induced
      internalization, but the underlying mechanisms of these processes and the role of
      beta-arrestins in the regulation of CB1R function are not completely understood.
      In this study, we followed CB1R internalization using confocal microscopy and
      bioluminescence resonance energy transfer measurements in HeLa and Neuro-2a
      cells. We found that upon activation CB1R binds beta-arrestin2 (beta-arr2), but
      not beta-arrestin1. Furthermore, both the expression of dominant-negative beta
      arr2 (beta-arr2-V54D) and siRNA-mediated knock-down of beta-arr2 impaired the
      agonist-induced internalization of CB1R. In contrast, neither beta-arr2-V54D nor
      beta-arr2-specific siRNA had a significant effect on the constitutive
      internalization of CB1R. However, both constitutive and agonist-induced
      internalization of CB1R were impaired by siRNA-mediated depletion of clathrin
      heavy chain. We conclude that although clathrin is required for both constitutive
      and agonist-stimulated internalization of CB1R, beta-arr2 binding is only
      required for agonist-induced internalization of the receptor suggesting that the
      molecular mechanisms underlying constitutive and agonist-induced internalization
      of CB1R are different.

PMID- 23541636
TI  - Continuous stress promotes expression of VGF in melanotroph via suppression of
      dopamine.
AB  - Prolonged exposure to stress elicits profound effects on homeostasis that may
      lead to cryptogenic disorders such as chronic fatigue syndrome. To investigate
      the pathophysiology associated with the syndrome, we used a rat continuous stress
      (CS) model where the pituitary represents one of the most affected organs. Here
      we found that mRNA for VGF (non-acronymic), a member of the granin family, was
      induced specifically in the intermediate lobe (IL). This was matched by a
      concomitant increase at the peptide/protein level assessed by C-terminal
      antibody. Furthermore, the up-regulation of VGF was confirmed by
      immunohistochemistry in a subset of melanotrophs. VGF expression was altered in
      the IL of rats receivingthe dopamine D2 receptor agonist bromocriptine or the
      antagonist sulpiride. In vitro, dopamine dose-dependently decreased the mRNA
      levels in cultured melanotrophs. These findings suggest that VGF expression under
      CS is negatively regulated by dopaminergic neurons projecting from the
      hypothalamus.

PMID- 23541637
TI  - Aldosterone-induced ENaC and basal Na+/K+-ATPase trafficking via protein kinase
      D1-phosphatidylinositol 4-kinaseIIIbeta trans Golgi signalling in M1 cortical
      collecting duct cells.
AB  - Aldosterone regulates Na(+) transport in the distal nephron through multiple
      mechanisms that include the transcriptional control of epithelial sodium channel
      (ENaC) and Na(+)/K(+)-ATPase subunits. Aldosterone also induces the rapid
      phosphorylation of Protein Kinase D1 (PKD1). PKD isoforms regulate protein
      trafficking, by the control of vesicle fission from the trans Golgi network (TGN)
      through activation of phosphatidylinositol 4-kinaseIIIbeta (PI4KIIIbeta). We
      report rapid ENaCgamma translocation to the plasma membrane after 30 min
      aldosterone treatment in polarized M1 cortical collecting duct cells, which was
      significantly impaired in PKD1 shRNA-mediated knockdown cells. In PKD1-deficient
      cells, the ouabain-sensitive current was significantly reduced and Na(+)/K(+)
      ATPase alpha and beta subunits showed aberrant localization. PKD1 and PI4KIIIbeta
      localize to the TGN, and aldosterone induced an interaction between PKD1 and
      PI4KIIIbeta following aldosterone treatment. This study reveals a novel mechanism
      for rapid regulation of ENaC and the Na(+)/K(+)-ATPase, via directed trafficking
      through PKD1-PI4KIIIbeta signalling at the level of the TGN.

PMID- 23541638
TI  - Radioisotope imaging of microRNA-9-regulating neurogenesis using sodium iodide
      sympoter.
AB  - Since microRNAs (miRNA, miR) are known to be critical in various cellular
      processes and diseases, non-invasive molecular imaging system for miRNA is very
      important for imaging cellular therapy and disease diagnosis. In this study, we
      developed a radionuclide imaging system for miR-9 using sodium iodide symporter
      (NIS). During neuronal differentiation of P 19 cells induced by the treatment of
      retinoic acid (RA), in vitro and in vivo imaging demonstrated that the expression
      and activity of NIS from the miR-9 NIS reporter gene was clearly repressed by the
      increased expression and functional activity of miR-9 that bound with the target
      sequences in the NIS reporter gene and resulted in destabilized the
      transcriptional activity of NIS gene, compared with the undifferentiated P19
      cells. The decreased activity of NIS from the differentiated P19 cells resulted
      in low uptake of radionuclide and decreased radioisotope signals. The NIS
      reporter gene-based miRNA imaging system showed a great specificity of imaging
      miRNA biogenesis during cellular developments. The miRNA NIS reporter gene will
      provide high sensitive imaging for visualizing miRNA-regulating cellular
      developments and diseases.

PMID- 23541639
TI  - Time in radiation oncology - keep it short!

PMID- 23541640
TI  - Always on a Friday: referral pattern for metastatic spinal cord compression.

PMID- 23541641
TI  - Three-dimensional summation of rectal doses in brachytherapy combined with
      external beam radiotherapy for prostate cancer.
AB  - BACKGROUND AND PURPOSE: To determine the dose constraints for rectal bleeding in
      brachytherapy (BRT) combined with external beam radiotherapy (EBRT). MATERIALS
      AND METHODS: Post-BRT, pelvic computed tomography images were used for subsequent
      EBRT planning and BRT postplans in 37 patients. The physical doses for each plan
      were converted to biologically effective doses, and corresponding voxel doses
      were integrated to plot the summed dose-volume histogram (sum-DVH). Between 5
      patients with (bled-pts) and 32 without (spared-pts) grade 2 or 3 rectal
      bleeding, the differences in the mean minimal dose (rDn) covering the rectal
      volume of 0.5-10.0 cc and the rectal volume (rVn) receiving the calculated dose
      of 20-150Gy were compared. RESULTS: The differences in the summed-rDn were
      determined by BRT exposure, while those of the summed-rVn were determined in the
      low-dose range and superimposed in the high-dose range by EBRT exposure. Of the
      13 patients with rV150 of >1.2 cc, 4 were bled-pts (30.8%). Of the 24 patients
      with rV150 of <= 1.2cc, 1 was a bled-pts (4.2%) (p=0.024; odds ratio, 10.2; CI
      (95%), 1.0-104.3). CONCLUSIONS: The mono-scale DVH analysis is a promising method
      for exploring the threshold for rectal bleeding in combined radiotherapy.

PMID- 23541642
TI  - Uncertainties in image guided adaptive cervix cancer brachytherapy: impact on
      planning and prescription.

PMID- 23541643
TI  - A dose escalation study with intensity modulated radiation therapy (IMRT) in
      T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and
      hypopharynx using a simultaneous integrated boost (SIB) approach.
AB  - BACKGROUND: The simultaneous integrated boost (SIB) technique with dose per
      fraction slightly higher than 2Gy offers the advantages of shortening the
      treatment time and increasing the biologically equivalent dose to the tumor. This
      study was designed to evaluate the feasibility of a dose-escalating radiotherapy
      treatment by using a SIB-IMRT approach in patients with early and moderately
      advanced head and neck cancers. MATERIALS AND METHODS: Fifty-seven consecutive
      patients with pharyngo-laryngeal T2N0 or T2N1, or laryngeal T3N0 SCC were
      included. The therapeutic PTVs were treated according to three consecutive dose
      levels i.e., 69 Gy in 30 fractions of 2.3 Gy (dose level I), 72 Gy in 30
      fractions of 2.4 Gy (dose level II) or 75 Gy in 30 fractions of 2.5 Gy (dose
      level III). The prophylactic PTVs received a dose of 55.5 Gy delivered in 30
      fractions of 1.85 Gy. The primary endpoint of the study was acute toxicity
      assessed during treatment and during the first 3 months following the completion
      of radiotherapy. The secondary endpoints included loco-regional control, disease
      free survival, overall survival and late toxicity at 2 years of follow-up. The
      study design allowed patients to be enrolled in the second dose level group if no
      more than 10% of grade 4 acute toxicity was observed on the first dose level
      group within 3 months after the completion of IMRT, and so on for the third level
      group. RESULTS: Forty-four men and 13 women were included in the trial. The
      majority of them presented with oropharyngeal cancer (53%) and laryngeal cancer
      (33%). Only 3 patients developed grade 4 acute mucositis during treatment, one in
      each dose level. Thirty-two patients (56%) experienced grade 3 toxicity, mostly
      dermatitis and mucositis, without any significant difference between the groups.
      Late grade 1 and 2 xerostomia was seen in 53% and 33% of patients, respectively.
      Transient grade 4 late toxicity was observed in 16% of all patients and was
      equally distributed among the groups. The 2-year loco-regional control was 82%
      for all 3 groups (79% dose level I, 88% dose level II, 79% dose level III). The 2
      year overall survival was 89% for dose level I and II, and 95% for dose level
      III. CONCLUSIONS: This dose escalation SIB-IMRT protocol was safe and effective
      as the sole treatment of early and moderately advanced SCC of head and neck. No
      toxicity difference was observed between the groups.

PMID- 23541644
TI  - Helical tomotherapy and intensity modulated proton therapy in the treatment of
      dominant intraprostatic lesion: a treament planning comparison.
AB  - PURPOSE: To compare helical tomotherapy (HT) and intensity modulated proton
      therapy (IMPT) for prostate cancer irradiation while concomitantly boosting
      dominant intraprostatic lesions (DILs). METHODS AND MATERIALS: Treatment plans of
      seven patients were designed for HT and IMPT (pencil beam size: 3mm sigma). The
      prescribed median PTV/DIL doses were 71.4/100 Gy in 28 fractions, while
      satisfying "safe" dose constraints for organs at risks (OARs) including rectum,
      bladder, femoral heads, penile bulb and urethra. The planner could further reduce
      the dose to OARs if PTV/DIL constraints were reached. RESULTS: IMPT achieved
      better dose conformity (CI=1.11 vs 1.31, p<0.05) and coverage (V95%=97.3% vs
      95.3%, p<0.05) in PTV. Concerning DIL volumes, both techniques delivered the
      prescribed dose (D median: HT=100 Gy, IMPT=102.1 Gy) with similar dose conformity
      (CI: HT=1.49, IMPT=1.44) and same dose homogeneity, D99%, D1%, while satisfying
      the OARs constraints. Excepting urethra, the sparing of OARs was significantly
      better with IMPT; in general, the lower the dose, the greater the benefit of
      IMPT. Normal tissue complication probabilities for the rectum were in favor of
      IMPT with an absolute reduction of 3-8%, depending on the NTCP model (p<0.05).
      CONCLUSIONS: Both techniques allowed delivering 100 Gy to DILs, while complying
      with the OARs constraints. IMPT was superior in sparing OARs for doses up to
      approximately 70 Gy, with larger benefit at lower doses.

PMID- 23541646
TI  - Glycyrrhetinic acid and its analogs: a new class of antifilarial agents.
AB  - Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a
      few have been evaluated for their biological significance. As part of our drug
      discovery program for antifilarial agents from Indian medicinal plants, the roots
      of G. glabra were chemically investigated, which resulted in the isolation and
      characterization of an antifilarial agent, glycyrrhetinic acid (GA, 1a) effective
      against microfilariae (mf) in vitro (LC100: 12.5 MUM; IC50: 1.20 MUM), but was
      inactive against adult worms. Further, GA (1a) was converted into six analogs (2a
      7a) and their antifilarial potential was evaluated by studying in vitro motility
      and MTT reduction assays employing mf and adult worms of Brugia malayi. The
      results showed that out of six GA analogs, the benzyl amide analog (6a) killed
      adults and mf at 25 and 50 MUM concentration, respectively, and inhibited 49% MTT
      reduction potential of the adult parasites. The IC50 values were found to be 8.8
      and 2.2 MUM for adults and mf, respectively. The SI of the compound was >60. On
      the other hand the octylamide analog (7a) required much higher concentration to
      adversely affect the parasites. Finally, both active amide analogs (6a and 7a)
      were in vivo evaluated using B. malayi-jird model, which showed that analog 6a
      possesses promising macrofilaricidal activity at 100mg/kg, s.c. *5 days and
      around 40% of the treated animals showed calcified masses of worm fragments in
      peritoneal cavity of the animals. To the best of our knowledge this is the first
      ever report on the antifilarial potential of GA analogs. Further work on
      optimization of the antifilarial lead is under progress.

PMID- 23541645
TI  - Uncertainty analysis for 3D image-based cervix cancer brachytherapy by repetitive
      MR imaging: assessment of DVH-variations between two HDR fractions within one
      applicator insertion and their clinical relevance.
AB  - PURPOSE: To investigate dosimetric uncertainties of MRI-based cervix cancer
      brachytherapy, when applying two HDR fractions for each applicator insertion and
      their clinical relevance. METHODS: 21 patients with 84 MRI-examinations and
      fractions were investigated. After insertion of the MRI compatible tandem-ring
      applicator, an MRI-set was recorded and the treatment plan optimised for the
      first fraction. Prior to the second fraction 16-20 h later a second MRI-set was
      recorded, and the dose distribution from the plan of the previous day
      superimposed and analysed. The same procedure was repeated for fractions 3 and 4.
      Dose from EBRT and brachytherapy was normalised to 2 Gy-fractionation (EQD2),
      added up to a total dose, and compared to a calculated total dose if only 1 MRI
      examination per insertion is available. RESULTS: The total D(90) for High risk
      (HR) CTV was 1.2+/-2.7 Gy(alphabeta10) (1+/-3%) (mean+/-1SD) lower by individual
      MRI-evaluation of each fraction compared to 1 MRI per insertion. The D(2cm(3))
      increased by 0.7+/-4.7 Gy(alphabeta3) (1+/-6%) for bladder, 1.1+/-2.4
      Gy(alphabeta3) (2+/-4%) for rectum and decreased by 0.8+/-3.4 Gy(alphabeta3) (1+/
      5%) for sigmoid. For HR CTV the individual approach did not identify any case
      with a decrease of D(90) >5 Gy(alphabeta10). For the bladder 3 cases, for the
      rectum no case and for the sigmoid 1 case was identified with an increase of
      D(2cm(3)) >5 Gy(alphabeta3). For the bladder all dose variations of more than 5
      Gy(alphabeta3) could have been avoided by ensuring a constant bladder filling.
      Individual MRI-evaluation did not determine any case where dose constraints were
      not fulfilled. CONCLUSIONS: For the treatment schedule as applied in this study,
      geometric differences between applicator, target and OAR result in overall
      dosimetric changes, which seem to be of minor relevance in regard to clinical
      dose volume constraints applied at present.

PMID- 23541647
TI  - Synthesis and biological evaluation of Foscan(r) bile acid conjugates to target
      esophageal cancer cells.
AB  - Porphyrins and chlorins such as Foscan(r) have a natural proclivity to accumulate
      in cancer cells. This trait has made them good candidates for photosensitizers
      and as imaging agents in phototherapy. In order to improve on cellular
      selectivity to lower post-treatment photosensitivity bile acid porphyrin
      bioconjugates have been prepared and investigated in esophageal cancer cells.
      Bile acids which are known to selectively bind to, or be readily taken up by
      cancer cells were chosen as targeting moieties. Synthesis of the conjugates was
      achieved via selective nucleophilic monofunctionalization of 5,10,15,20
      tetrahydroxyphenylporphyrins with propargyl bromide followed by Cu(I) mediated
      cycloaddition with bile acid azides in good yields. The compounds were readily
      taken up by esophageal cancer cells but showed no PDT activity.

PMID- 23541648
TI  - Hydrophilic chlorin-conjugated magnetic nanoparticles--potential anticancer agent
      for the treatment of melanoma by PDT.
AB  - This Letter reports the synthesis and the characterization of two new water
      stable and soluble photosensitizer-conjugated magnetic nanoparticles (PS-MNPs)
      composed of an iron oxide magnetic core coated with a biocompatible dextran shell
      bearing polyaminated chlorin p6. Designed to improve cancer cell targeting, these
      photosensitizers were assayed for their antitumour activity against two variants
      of B16 mouse melanoma cell line (B16F10 and B16G4F, with or without melanin,
      respectively). Cell viability measurements demonstrated that PS-MNPs were more
      phototoxic than PEI-chlorin p6 making these photosensitizers promising for
      further in vitro and in vivo investigations.

PMID- 23541649
TI  - A diazen-1-ium-1,2-diolate analog of 7-azabenzobicyclo[2.2.1]heptane: synthesis,
      nitric oxide and nitroxyl release, in vitro hemodynamic, and anti-hypertensive
      studies.
AB  - 1-(7-Azabenzobicyclo[2.2.1]heptane)diazen-1-ium-1,2-diolate (16) was designed
      with the expectation that it would act as a dual nitric oxide (NO) and nitroxyl
      (HNO) donor that is not carcinogenic or genotoxic. Compound 16, with a suitable
      half-life (17.8 min) in PBS at pH 7, released NO (19%) and HNO (22%) during a 2h
      incubation in PBS at pH 7. In addition, compound 16 exhibited a significant in
      vitro positive inotropic effect, increased the rates of contraction and
      relaxation, and increased coronary flow rate, but did not induce a chronotropic
      effect. Furthermore, compound 16 (13.7 mg kg(-1), po dose) provided a significant
      reduction in the blood pressure of mice up to 3h post-drug administration. All
      these data suggest that compound 16 constitutes an attractive 'lead-compound'
      that could have potential applications to treat cardiovascular disease(s) such as
      congestive heart failure.

PMID- 23541650
TI  - C1 and N5 derivatives of cerpegin: synthesis of a new series based on structure
      activity relationships to optimize their inhibitory effect on 20S proteasome.
AB  - Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4
      dione) were designed and synthesized in high yield by a new method, combining
      several C(1) and N(5) substituents. All compounds were tested for their
      inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified
      mammalian 20S proteasome. Only one molecule inhibited both CT-L and PA
      activities. Sixteen molecules specifically inhibited PA at the micromolar range,
      out of which fourteen had IC50 values around 5 MUM and two had IC50 values closer
      to 2 MUM. Except in one case, neither calpain I nor cathepsin B was inhibited. In
      silico docking suggests a unique mode of binding of the most efficient compounds
      to the beta1 catalytic site (PA activity) in relation to the chemical nature of
      C(1) substituents.

PMID- 23541651
TI  - Inhibitors of the p53/hdm2 protein-protein interaction-path to the clinic.
AB  - A growing number of the elements identified in intracellular signaling events
      that affect cell growth and transformation are proteins that physically interact
      with each other via domains or specifically recognized amino acid sequences. Some
      of these intracellular protein-protein interactions are attractive targets for
      anticancer targeted therapy, but progress in this field has been compromised by
      the paucity of compounds with suitable biological profiles and pharmacological
      properties. This Letter covers salient achievements in the identification and
      development of inhibitors of the p53-hdm2 protein-protein interaction, and
      highlights different screening techniques and structure-based design approaches
      that may be brought to bear on the discovery and development of inhibitors of
      other therapeutically relevant intracellular protein-protein interactions.

PMID- 23541652
TI  - The RML of lymph node metastasis was superior to the LODDS for evaluating the
      prognosis of gastric cancer.
AB  - OBJECTIVE: The aim of the study was to investigate the most appropriate system
      for categorization of metastatic lymph nodes among N staging (according to the
      7th edition UICC/AJCC TNM Classification for Gastric Cancer), ratio between
      metastatic and examined lymph nodes (RML) staging, negative lymph nodes (NLN)
      staging and log odds of positive lymph nodes (LODDS) staging for evaluation the
      overall survival (OS) of gastric cancer. METHODS: We reviewed clinicopathological
      data of 372 gastric cancer patients who underwent radical gastrectomy plus
      extended lymphadenectomy with the purpose of evaluating the differences in the OS
      according to different categories of metastatic lymph nodes. RESULTS: Univariate
      and multivariate analysis of data significantly identified the degree of
      differentiation (HR = 1.404, p = 0.015), T staging (according to the 7th edition
      UICC/AJCC TNM Classification for Gastric Cancer) (HR = 1.568, p = 0.024) and the
      RML staging (HR = 1.479, p = 0.030) as independent predictors of the OS. However,
      RML staging was identified as the most appropriate for evaluating the OS of
      gastric cancer patients following radical gastrectomy plus extended
      lymphadenectomy rather than N staging, NLN staging and LODDS staging by using the
      case-control matched analysis. With the further stratified analysis, we
      demonstrated that RML staging had the best prognostic homogeneity than LODDS
      staging, NLN staging or N staging. CONCLUSIONS: RML staging was the best system
      for prediction the OS of the gastric cancer patients following radical
      gastrectomy plus extended lymphadenectomy, rather than LODDS staging, NLN staging
      or N staging.

PMID- 23541653
TI  - Probing the sequence and structure of in vitro synthesized antisense and target
      RNAs from the replication control system of plasmid pMV158.
AB  - Antisense RNAII is a replication control element encoded by promiscuous plasmid
      pMV158. RNAII binds to its complementary sequence in the copG-repB mRNA, thus
      inhibiting translation of the replication initiator repB gene. In order to
      initiate the biochemical characterization of the pMV158 antisense RNA-mediated
      control system, conditions for in vitro transcription by T7RNA polymerase were
      set up that yielded large amounts of antisense and target run-off products able
      to bind to each other. The run-off antisense transcript was expected, and
      confirmed, to span the entire RNAII as synthesized by the bacterial RNA
      polymerase, including the intrinsic transcription terminator at its 3'-terminus.
      On the other hand, two different target transcripts, mRNA60 and mRNA80, were
      produced, characterized and tested for efficient binding to the antisense
      product. The mRNA60 and mRNA80 run-off transcripts supposedly spanned 60 and 80
      nucleotides, respectively, on the copG-repB mRNA and lacked terminator-like
      structures at their 3'-termini. Probing of the sequence and conformation of the
      main products, along with modeling of their secondary structures, showed that
      both target transcripts were actually longer-than-expected, and contained a 3'
      terminal hairpin wherein the extra nucleotides base-paired to the expected 3'
      terminus of the corresponding run-off transcript. These longer products were
      proposed to arise from the RNA-dependent polymerizing activity of T7RNA
      polymerase on correct run-off transcripts primed by extremely short 3'
      selfcomplementarity. Seizing of the target mRNA sequence complementary to the 5'
      terminus of RNAII in a stable 3'-terminal hairpin generated by this activity
      seemed to cause a 3-fold decrease in the efficiency of binding to the antisense
      RNA.

PMID- 23541654
TI  - Conical coils counter-current chromatography for preparative isolation and
      purification of tanshinones from Salvia miltiorrhiza Bunge.
AB  - Modern counter-current chromatography (CCC) originated from the helical coil
      planet centrifuge. Recently, spiral coils were found to possess higher separation
      efficiency in both the retention of stationary phase and solutes resolution than
      other CCC coils like the helical and toroidal coils used on type-J CCC and cross
      axis CCC. In this work, we built a novel conical coil CCC for the preparative
      isolation and purification of tanshinones from Salvia miltiorrhiza Bunge. The
      conical coils were wound on three identical upright tapered holders in head-to
      tail and left-handed direction and connected in series. Compared with helical and
      spiral coil CCC, conical coil CCC not only placed CCC column in a two-dimensional
      centrifugal field, but also provided a potential centrifugal force gradient both
      in axial and radial directions. The extra centrifugal gradient made mobile phase
      move faster and enabled CCC much higher retention of stationary phase and better
      resolution. As a result, higher efficiency has been obtained with the solvent
      system of hexane-ethyl acetate-methanol-water (HEMWat) with the volume ratio of
      5:5:7:3 by using conical coil CCC apparatus. Four tanshinones, including
      cryptotanshinone (1), tanshinone I (2), 1,2-dihydrotanshinquinone (3) and
      tanshinone IIA (4), were well resolved from 500mg to 1g crude samples with high
      purity. Furthermore, the conical coil CCC can make a much higher solid phase
      retention, which makes it to be a powerful separation tool with high throughput.
      This is the first report about conical coil CCC for separation of tanshinones and
      it may also be an important advancement for natural products isolation.

PMID- 23541655
TI  - Simultaneous speciation and preconcentration of ultra trace concentrations of
      mercury and selenium species in environmental and biological samples by hollow
      fiber liquid phase microextraction prior to high performance liquid
      chromatography coupled to inductively coupled plasma mass spectrometry.
AB  - Nowadays, hollow fiber membrane extraction techniques are widely used due to the
      high enrichment factors obtained with many different types of analytes and
      samples. In this paper, we propose a new analytical method that allows the
      simultaneous extraction of methylmercury, inorganic mercury and Se(4+) and
      determination by high performance liquid chromatography coupled to inductively
      coupled plasma mass spectrometry (HPLC-ICP-MS). The detection limits obtained are
      very low (110-230ng/L) with relative standard deviations below 15% for all the
      analytes and averaged recoveries in fortified samples in the range of 71-99%. The
      precision of the analytical method is very good which overcomes one of the most
      important shortcomings of membrane extraction techniques. Several variables were
      studied to get optimal extraction conditions for the analytes. This method has
      been validated with real world samples such as water (tap, river and estuarine)
      and human blood plasma. 

PMID- 23541656
TI  - Determination of organophosphate esters in water samples using an ionic liquid
      based sol-gel fiber for headspace solid-phase microextraction coupled to gas
      chromatography-flame photometric detector.
AB  - A simple, low-cost and sensitive method for determining organophosphate esters
      (OPEs) in water samples has been developed based on headspace solid-phase
      microextraction (SPME) followed by gas chromatography-flame photometric detector.
      The ionic liquid (1-allyl-3-methylimidazolium tetrafluoroborate, [AMIM][BF4])
      based coating was developed by sol-gel technology and employed for extracting
      analytes. The prepared coating performed stably at high temperatures (up to 335
      degrees C) and with a range of solvents. It can be used at least 200 times
      without an obvious decrease in extraction efficiency. The extraction capability
      of the new fiber was much higher than polydimethylsiloxane (PDMS),
      polydimethylsiloxane/divinylbenzene (PDMS/DVB) and polyacrylate (PA) fibers. The
      experimental parameters that influenced the extraction efficiency, including
      extraction time, extraction temperature, stirring rate and ionic strength were
      investigated and optimized. Under the optimal conditions, the method detection
      limits (S/N=3) were in the range of 0.7-12ngL(-1), and the limits of
      quantification (S/N=10) were between 1.0 and 28ngL(-1). The repeatability of a
      single fiber varied from 3.3 to 7.6% (intra-day precision, n=6) and 4.3 to 8.9%
      (inter-day precision, n=6). The reproducibility of fiber-to-fiber (n=6) was in
      the range of 3.1-9.4%. The proposed method was applied successfully for the
      determination of OPEs in lake water, wastewater, sewage treatment plant effluent,
      and tap water with recoveries varying from 75.2 to 101.8%. The results
      demonstrate that the proposed method is highly effective for analyzing OPEs in
      water samples. 

PMID- 23541657
TI  - Immunocapture couples with matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry for rapid detection of type 1 dengue virus.
AB  - A facile method for accurate detection of type 1 dengue virus (DV1) infection
      from complex biological mixtures, using type specific immunocapture coupled with
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS), was developed. The biological mixtures were treated with magnetic
      particles coated with a monoclonal antibody directly against type 1 dengue virus.
      After immunocapture purification, the DV1 was eluted with 30% acetic acid,
      directly spotted with seed-layer method, and analyzed by MALDI-TOF MS for DV1
      capsid protein. The detection limit of the assay was ~10(5)pfu/mL by MALDI-TOF
      MS. The immunocapture could unambiguously differentiate the DV1 from other
      serotypes of the dengue viruses and Japanese encephalitis virus, and could be
      used as a specific probe to detect DV1 from complex biological mixtures.

PMID- 23541658
TI  - Community-based programs to improve prevention and management of hypertension:
      recent Canadian experiences, challenges, and opportunities.
AB  - High blood pressure (BP) is the greatest risk of ill health and an early death
      worldwide. It is a key factor in the development of atherosclerosis, the main
      cause of vascular and cerebrovascular diseases, and is causally linked to kidney
      failure and dementia. Healthy lifestyle choices coupled with effective,
      population-based prevention strategies, early detection, and optimal treatment
      and control of high BP can substantially reduce the burden of vascular and
      cerebrovascular diseases. Considering the projected increases in the risk factors
      responsible for these conditions, it is imperative that effective population
      based prevention strategies are developed, evaluated, and scaled-up. Extensive
      and rigourous evidence supports the promotion of healthy lifestyle choices to
      maintain low BP and prevent associated chronic diseases. Community-based programs
      are the prime tool for implementing a population strategy of prevention. Their
      aim is to shift the distribution of risk factors to lower levels across entire
      populations. Despite their great potential and more than a 4-decade history, it
      remains unclear to what extent such programs can be effectively implemented,
      scaled-up and sustained. We provide a broad overview of community-based programs
      implemented to address cardiovascular disease risk factors, focus on the recent
      Canadian experience in this area, and highlight the main challenges and
      opportunities currently associated with them. Recent Canadian initiatives have
      shown encouraging results, some of them focusing on high-risk subgroups. These
      initiatives demonstrate feasibility and benefits of implementing community-based
      programs for the prevention and management of cardiovascular disease in Canada.

PMID- 23541659
TI  - Combination antihypertensive treatment with aliskiren and blockers of the Renin
      Angiotensin system-reassurance but with a note of caution.

PMID- 23541661
TI  - The use of captopril in rheumatoid arthritis: combining treatment targets!

PMID- 23541660
TI  - The 2013 Canadian Hypertension Education Program recommendations for blood
      pressure measurement, diagnosis, assessment of risk, prevention, and treatment of
      hypertension.
AB  - We updated the evidence-based recommendations for the diagnosis, assessment,
      prevention, and treatment of hypertension in adults for 2013. This year's update
      includes 2 new recommendations. First, among nonhypertensive or stage 1
      hypertensive individuals, the use of resistance or weight training exercise does
      not adversely influence blood pressure (BP) (Grade D). Thus, such patients need
      not avoid this type of exercise for fear of increasing BP. Second, and
      separately, for very elderly patients with isolated systolic hypertension (age 80
      years or older), the target for systolic BP should be < 150 mm Hg (Grade C)
      rather than < 140 mm Hg as recommended for younger patients. We also discuss 2
      additional topics at length (the pharmacological treatment of mild hypertension
      and the possibility of a diastolic J curve in hypertensive patients with coronary
      artery disease). In light of several methodological limitations, a recent
      systematic review of 4 trials in patients with stage 1 uncomplicated hypertension
      did not lead to changes in management recommendations. In addition, because of a
      lack of prospective randomized data assessing diastolic BP thresholds in patients
      with coronary artery disease and hypertension, no recommendation to set a
      selective diastolic cut point for such patients could be affirmed. However, both
      of these issues will be examined on an ongoing basis, in particular as new
      evidence emerges.

PMID- 23541662
TI  - Percutaneous closure of a very large left atrial appendage using the Amplatzer
      amulet.
AB  - Although percutaneous left atrial appendage (LAA) closure is becoming a common
      procedure worldwide, there are still some anatomic limitations. The size of the
      LAA is one of the current limitations as the most popular devices do not allow
      the closure of very large LAAs. The new Amplatzer Cardiac Plug 2, also called
      "Amulet," has been redesigned not only to improve delivery and safety but also to
      allow the closure of larger LAAs. The present report describes the successful
      closure of a very large LAA using the Amulet. 

PMID- 23541663
TI  - Five years of chronic total confusion.

PMID- 23541664
TI  - The evolution of a Canadian Hypertension Education Program recommendation: the
      impact of resistance training on resting blood pressure in adults as an example.
AB  - Ever since the first set of hypertension recommendations which were generated
      from the Canadian Hypertension Education Program, lifestyle and health behaviour
      have been a key focus. An initial recommendation focused on the benefits of
      aerobic exercise to reduce resting blood pressure (BP). However, until the 2013
      edition, resistance exercise (RT) was not included. The current article describes
      a meta-analysis that was conducted which helped inform the creation of the newly
      introduced recommendation. Literature searches were conducted in 4 electronic
      databases. Inclusion criteria included: (1) randomized controlled trials with 4
      week minimum, RT-alone intervention arms; (2) BP-lowering as the primary outcome;
      (3) human, adult participants; and (4) reporting control data, baseline, and
      postintervention resting systolic BP and diastolic BP. Nine studies (11
      intervention groups, 452 participants) were identified. The analyses indicated
      that diastolic BP was significantly reduced (-2.2 mm Hg; 95% confidence interval,
      -3.9 to -0.5) in those randomized to RT compared with control participants. In
      contrast, no statistically significant change in systolic BP (-1.0 mm Hg; 95%
      confidence interval, -3.4 to 1.4) was observed. None of the studies found RT to
      increase BP and no adverse effects of RT were explicitly reported. Results
      suggest that participation in RT is not harmful and does not increase BP.
      However, more evidence is needed before recommending RT as a specific BP-lowering
      therapy.

PMID- 23541665
TI  - Renal sympathetic denervation for resistant hypertension.
AB  - Resistant hypertension is an increasingly prevalent health problem associated
      with important adverse cardiovascular outcomes. The pathophysiology that
      underlies this condition involves increased function of both the sympathetic
      nervous system and the renin-angiotensin II-aldosterone system. A crucial link
      between these 2 systems is the web of sympathetic fibres that course within the
      adventitia of the renal arteries. These nerves can be targeted by applying
      radiofrequency energy from the lumen of the renal arteries to renal artery walls
      (percutaneous renal sympathetic denervation [RSD]), an approach that has
      attracted great interest. This paper critically reviews the evidence supporting
      the use of RSD. Small studies suggest that RSD can produce dramatic blood
      pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients,
      the mean fall in blood pressure at 6 months in patients who received the
      treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD
      in the treatment of resistant hypertension. These include the small number of
      patients studied; the lack of any placebo-controlled evidence; the fact that
      blood pressure outcomes were based on office assessments, as opposed to 24-hour
      ambulatory monitoring; the lack of longer-term efficacy data; and the lack of
      long-term safety data. Some of these concerns are being addressed in the ongoing
      Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3)
      trial. The first percutaneous RSD system was approved by Health Canada in the
      spring of 2012. But until more and better-quality data are available, this
      procedure should generally be reserved for those patients whose resistant
      hypertension is truly uncontrolled.

PMID- 23541666
TI  - No increase in adverse events during aliskiren use among ontario patients
      receiving angiotensin-converting enzyme inhibitors or angiotensin-receptor
      blockers.
AB  - BACKGROUND: Some evidence suggests that the direct renin inhibitor aliskiren may
      increase the risk of severe hyperkalemia, stroke, or acute kidney injury (AKI)
      when prescribed with angiotensin-converting enzyme inhibitors (ACEi's) or
      angiotensin-receptor blockers (ARBs). The extent to which concomitant treatment
      increases the risk of these outcomes in routine clinical practice is unknown. We
      addressed this issue with the use of administrative databases. METHODS: We
      established a cohort of Ontarians treated with an ACEi or an ARB. Within this
      cohort, we conducted 3 case-control studies. Cases were patients hospitalized
      with 1 of 3 outcomes (hyperkalemia, AKI, or stroke). In each analysis, we
      identified up to 5 matched control subjects for each case. Conditional logistic
      regression was used to examine the association between hospitalization for each
      outcome and the use of aliskiren in the preceding 60 days. RESULTS: Among 903,346
      patients aged 66 years and older treated with an ACEi or ARB during the 28-month
      study period, we identified 4235 hospitalized with hyperkalemia, 18,231
      hospitalized with AKI, and 8283 hospitalized with stroke. After extensive
      multivariable adjustment, aliskiren therapy was not associated with a significant
      increase in the risk of hospitalization for hyperkalemia, AKI, or stroke. We
      found similar results in stratified analyses of patients with and without a
      history of chronic kidney disease, diabetes, or heart failure. CONCLUSIONS: Among
      community-dwelling patients aged 66 years and older receiving therapy with an
      ACEi or an ARB, aliskiren use was not associated with hospitalization for
      hyperkalemia, AKI, or stroke.

PMID- 23541667
TI  - Polyunsaturated fatty acid-derived chromones exhibiting potent antioxidant
      activity.
AB  - The marine polyunsaturated lipid-derived natural product all-(Z)-5,7-dihydroxy-2
      (4Z,7Z,10Z,13Z,16Z-nonadecapentaenyl) (1) and four analogs 5-8 have been
      synthesized and evaluated as antioxidants in two cell-based assays. The natural
      product 1 and the analog 5 exhibited interesting antioxidant effects with IC50
      values of 14+/-9 and 29+/-3MUM, respectively, in a cellular lipid peroxidation
      antioxidant activity assay using HepG2 cells. Moreover, in the HepG2 cellular
      antioxidant activity assay, the natural product 1 exhibited strong protective
      effects against reactive oxygen species with an IC50=160+/-25MUM.

PMID- 23541668
TI  - Synthetic oligoureas of metaphenylenediamine mimic host defence peptides in their
      antimicrobial behaviour.
AB  - Oligomeric ureas of m-phenylenediamine target anionic DMPG
      (dimyristoylphosphatidylglycerol) and possess promise as antimicrobial agents.
      Their similar size, shape and hydrophobicity to helical antimicrobial peptides
      (AMPs) may be important for activity to exist and the ability of these compounds
      to insert into a well ordered lipid environment.

PMID- 23541669
TI  - Identification and design of a novel series of MGAT2 inhibitors.
AB  - [Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target
      for therapeutic treatment of diabetes, obesity and other diseases which together
      constitute the metabolic syndrome. In this Letter we report our discovery and
      optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of
      the series and a detailed discussion around some key parameters monitored and
      addressed during the lead generation phase will be given. The in vivo results
      from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows
      a significant reduction (68% inhibition relative to naive, p<0.01) in plasma
      triacylglycerol (TAG) concentration.

PMID- 23541670
TI  - Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as
      potent JAK3 kinase inhibitors.
AB  - We report the discovery of a novel series of ATP-competitive Janus kinase 3
      (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial
      leads in this series, compounds 1a and 1h, showed promising potencies, but a lack
      of selectivity against other isoforms in the JAK family. Computational and
      crystallographic analysis suggested that the phenyl ether moiety possessed a
      favorable vector to achieve selectivity. Exploration of this vector resulted in
      the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating
      improved JAK family and kinase selectivity.

PMID- 23541671
TI  - Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1
      phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate.
AB  - We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1
      phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the
      difficulty of realising a phosphorylation step on the anomeric position of 2
      deoxyribose, and we discover that introduction of fluorine atoms on the 2
      position of 2-deoxyribose enables the phosphorylation step: in fact, the
      stability of the prodrugs increases with the degree of 2-fluorination. Stability
      studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2
      deoxyribose-1-phosphate in acidic and neutral conditions were conducted to
      confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2
      deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported.

PMID- 23541672
TI  - PEG mediated synthesis and pharmacological evaluation of some fluoro substituted
      pyrazoline derivatives as antiinflammatory and analgesic agents.
AB  - A new series of fluoro substituted pyrazoline derivatives 5a-g and 6a-g were
      synthesized in good to excellent yield from the corresponding pyrazole chalcones,
      4a-g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction
      medium. The newly synthesized compounds were characterized and screened for their
      in vivo antiinflammatory and analgesic activity. Compounds 5g and 6g were found
      to be more potent than standard drug Diclofenac and six other compounds 5b, 5c,
      5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to
      standard drug. Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant
      analgesic activity as compared to standard drug Aspirin.

PMID- 23541673
TI  - A potential rhodium cancer therapy: studies of a cytotoxic organorhodium(I)
      complex that binds DNA.
AB  - Described is a novel organorhodium(I) complex that is cytotoxic to the colon
      cancer cell line HCT116 and alters cell migration, DNA replication, and DNA
      condensation. Most importantly, the mechanism observed is not seen for the parent
      organorhodium dimer complex [{RhCl(COD)}2], RhCl3, or the free ligand/proligands
      (COD and 1-(n)butyl-3-methylimidazolium chloride). Thus, the activity of this
      organorhodium complex is attributable to its unique structure.

PMID- 23541674
TI  - Identification of metal ion binding peptides containing unnatural amino acids by
      phage display.
AB  - The bidentate metal binding amino acid bipyridylalanine (BpyAla) was incorporated
      into a disulfide linked cyclic peptide phage displayed library to identify metal
      ion binding peptides. Selection against Ni(2+)-nitrilotriacetic acid (NTA)
      enriched for sequences containing histidine and BpyAla. BpyAla predominated when
      selections were carried out at lower pH, consistent with the differential pKa's
      of histidine and BpyAla. Two peptides containing BpyAla were synthesized and
      found to bind Ni(2+) with low micromolar dissociation constants. Incorporation of
      BpyAla and other metal binding amino acids into peptide and protein libraries
      should enable the evolution of novel binding and catalytic activities.

PMID- 23541675
TI  - A second-order high resolution finite difference scheme for a structured
      erythropoiesis model subject to malaria infection.
AB  - We develop a second-order high-resolution finite difference scheme to approximate
      the solution of a mathematical model describing the within-host dynamics of
      malaria infection. The model consists of two nonlinear partial differential
      equations coupled with three nonlinear ordinary differential equations.
      Convergence of the numerical method to the unique weak solution with bounded
      total variation is proved. Numerical simulations demonstrating the achievement of
      the designed accuracy are presented. 

PMID- 23541676
TI  - Neurocognitive effects of methylphenidate on ADHD children with different DAT
      genotypes: a longitudinal open label trial.
AB  - The variable number of tandem repeat polymorphism in the 3'-untranslated region
      of the dopamine transporter gene (DAT) may influence the variability of the
      therapeutic response to methylphenidate (MPH) in Attention Deficit/Hyperactivity
      Disorder (ADHD). For this reason we evaluated the neuropsychological functioning
      after a prolonged period of MPH treatment and after a specific time from MPH
      suspension. Relationship between DAT VNTR genotypes and neurocognitive response
      to MPH was analyzed in a sample of 108 drug-naive ADHD patients. The performance
      of children with ADHD on measures of working memory, inhibition and planning was
      assessed at 4, 8 and 24 weeks and at 8 weeks after MPH withdrawal. Patients with
      9/9 genotype evidenced an improvement in response inhibition and working memory
      only at 4 weeks of treatment, in planning at 24 weeks of therapy and after 8
      weeks of MPH suspension. Patients with 9/10 showed an improvement in response
      inhibition at 4, 8 and 24 weeks of treatment, in planning at 24 weeks and after 8
      weeks of MPH suspension. Patients with 10/10 evidenced an improvement in response
      inhibition and working memory at 4, 8 and 24 weeks of treatment and in planning
      at 4, 8 and 24 weeks of treatment and after 8 weeks of suspension. These results
      indicate that the 9/9 ADHD genotype has a different response at 24 weeks
      treatment with MPH. 10/10 DAT allele seems to be associated with an increased
      expression level of the dopamine transporter and seems to mediate the MPH
      treatment response in ADHD patients.

PMID- 23541677
TI  - Topical brinzolamide for foveal schisis in juvenile retinoschisis.
AB  - We describe a case series of 4 consecutive patients diagnosed with X-linked
      retinoschisis seen at a pediatric ophthalmology clinic during a 3-year period.
      All patients were treated with topical brinzolamide; 3 patients experienced
      significantly decreased severity of macular cysts on OCT in at least one eye.

PMID- 23541678
TI  - Ixodes ricinus infestation in free-ranging cervids in Norway--a study based upon
      ear examinations of hunted animals.
AB  - Prevalence, abundance and instar composition of Ixodes ricinus as found on one
      ear collected from 1019 moose (Alces alces), red deer (Cervus elaphus) and roe
      deer (Capreolus capreolus), shot during hunting (August-December) 2001-2003, are
      reported. The animals originated from 15 coastal municipalities (CM), seven
      municipalities bordering to coastal municipalities (BCM) and four inland
      municipalities (IM), in Norway, between latitudes 58-66 degrees  N. I. ricinus
      occurred endemically in all CM and BCM up to 63 degrees 30' N, whereas it was non
      endemic further north and in the IM. This geographical distribution of the tick
      along the coast of southern Norway was largely in accordance with that reported
      as far back as the 1940s. Our results therefore did not indicate any large scale
      northwards expansion of I. ricinus in Norway during the 60 year-period between
      the two studies. However, the prevalence of infestation and tick abundance were
      significantly higher in CM as compared to BCM. The prevalence and abundance by
      month were highest during August and September, gradually decreasing towards
      December. The considerable prevalence of ticks in November, as well as findings
      in December, would seem to indicate a prolonged tick season as compared with the
      studies carried out 60 years ago. A total of 8920 ticks were isolated from 439 of
      the 603 animals examined in endemic municipalities, and the maximum number of
      ticks found on one single ear was 204. Attached adult ticks were primarily found
      among the long hairs at base of the ear, whereas nymphs and larvae were seen all
      over the outer surface of the pinna, for larvae especially at the edge and tip of
      the ear. Nymphs were the dominant instar, constituting 74% of the total tick
      count. The proportion of larvae and adult ticks was 13% and 12%. A significantly
      higher proportion of adult ticks and lower proportion of immature stages were
      found in moose, as compared to red deer and roe deer. The same apparently size
      associated preference of adult ticks was also found for adult animals (all
      species) as compared to calves. Other grossly detected ectoparasites included the
      lice Solenopotes burmeisteri in red deer and Damalinia meyeri in roe deer, and
      the deer ked fly, Lipoptena cervi, in moose and roe deer. This is believed to be
      the first systematic study on the instar composition by I. ricinus infestation in
      free-ranging cervids. The examination of ears from hunted cervids should be
      recognized as a rational way of obtaining data on the geographical distribution
      and abundance of this tick in nature.

PMID- 23541679
TI  - Checking the garbage bin for problems in the house, or how autophagy assists in
      antigen presentation to the immune system.
AB  - Macroautophagy was originally discovered as a nutrient salvage pathway during
      starvation. By now it has not only become clear that degradation of cytoplasmic
      constituents via transport by autophagosomes to lysosomes can be used for innate
      and adaptive immunity, but that the core machinery assists antigen presentation
      to the immune system by a variety of vesicular transport pathways. All of these
      rely on the presentation of small protein waste fragments, which are generated by
      a variety of catabolic pathways, including macroautophagy, on major
      histocompatibility complex (MHC) molecules. In this review, we will point out how
      classical macroautophagy, as well as phagocytosis and exocytosis, which both
      benefit from the core autophagic machinery, assist in antigen presentation on MHC
      class I and II molecules to CD8+ and CD4+ T cells, respectively. Finally to high
      light that macroautophagy is always intimately interconnected with cell death in
      addition to the various supported vesicular transport function, its role in
      lymphocyte, especially T cell, development and function will be discussed. From
      this body of work a picture is emerging that the core machinery of macroautophagy
      can be used for a variety of vesicular transport pathways and to modulate cell
      survival, besides its classical role in delivering intracellular material for
      lysosomal degradation. 

PMID- 23541681
TI  - The effect of mammography pain on repeat participation in breast cancer
      screening: a systematic review.
AB  - Uptake is crucial to reducing breast cancer mortality through screening. This
      review synthesised all available evidence on mammography pain as a deterrent to
      subsequent breast screening. Ten databases were searched. Studies containing
      empirical data relating mammography pain to breast screening re-attendance were
      included (n = 20). In the most robust studies asking women why they had not re
      attended, 25%-46% cited pain, equivalent to approximately 47,000-87,000 women per
      year in England. The most robust evidence for an association between pain
      experienced at a previous mammogram and subsequent rates of re-attendance
      suggests that women who previously experienced pain are more likely than those
      who did not to fail to re-attend: RR 1.34 (95% CI: 0.94-1.91). The complexity of
      the pain phenomenon and of screening behaviours must be recognised. However,
      there is sufficient evidence to conclude that painful mammography contributes to
      non-re-attendance. Given the importance of cumulative participation, effective
      pain-reducing interventions in mammography are needed.

PMID- 23541680
TI  - Oxidation-specific epitopes and immunological responses: Translational
      biotheranostic implications for atherosclerosis.
AB  - Oxidation-specific epitopes (OSE), present on oxidized LDL (OxLDL), apoptotic
      cells, cell debris and modified proteins in the vessel wall, accumulate in
      response to hypercholesterolemia, and generate potent pro-inflammatory, disease
      specific antigens. They represent an important class of 'danger associated
      molecular patterns' (DAMPs), against which a concerted innate immune response is
      directed. OSE are recognized by innate 'pattern recognition receptors', such as
      scavenger receptors present on dendritic cells and monocyte/macrophages, as well
      as by innate proteins, such as IgM natural antibodies and soluble proteins, such
      as C-reactive protein and complement factor H. These innate immune responses
      provide a first line of defense against atherosclerosis-specific DAMPs, and
      engage adaptive immune responses, provided by T and B-2 cells, which provide a
      more specific and definitive response. Such immune responses are ordinarily
      directed to remove foreign pathogens, such as those found on microbial pathogens,
      but when persistent or maladaptive, lead to host damage. In this context,
      atherosclerosis can be considered as a systemic chronic inflammatory disease
      initiated by the accumulation of OSE type DAMPs and perpetuated by maladaptive
      response of the innate and adaptive immune system. Understanding this paradigm
      leads to new approaches to defining cardiovascular risk and suggests new modes of
      therapy. Therefore, OSE have become potential targets of diagnostic and
      therapeutic agents. Human and murine OSE-targeting antibodies have been developed
      and are now being used as biomarkers in human studies and experimentally in
      translational applications of non-invasive molecular imaging of oxidation-rich
      plaques and immunotherapeutics. 

PMID- 23541682
TI  - Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in
      esophageal squamous cell carcinoma.
AB  - The anti-cancer activity of resveratrol in human esophageal squamous cell
      carcinoma (ESCC) was investigated focusing on the role of autophagy and its
      effects on apoptotic cell death. We demonstrated that resveratrol inhibits ESCC
      cell growth in a dose-dependent manner by inducing cell cycle arrest at the sub
      G1 phase and resulting in subsequent apoptosis. Mechanistically, resveratrol
      induced autophagy in the ESCC cells is AMPK/mTOR pathway independent. Since both
      pharmacological and genetic inhibition of autophagy enhanced the resveratrol
      induced cytotoxicity to the ESCC cells, this provided a novel strategy in
      potentiating the anti-cancer effects of resveratrol and other chemotherapeutic
      reagents in ESCC cancer treatment. 

PMID- 23541683
TI  - Toll-like receptor 3 expression inhibits cell invasion and migration and predicts
      a favorable prognosis in neuroblastoma.
AB  - To evaluate the clinical significance of TLR3 expression on neuroblastomas, we
      performed immunohistochemical study on archival tissues and in vitro studies on
      neuroblastoma cell lines. The results showed that positive TLR3 expression was
      associated with favorable histology and prognosis. Activation of TLR3 by
      polyinosinic:polycytidylic acid [poly(I:C)] treatment is effective to suppress
      cell migration and invasion and to decrease organized assembly of F-actin and
      filopodia formation, in TLR3-expressing SK-N-AS cells, which could be reversed by
      TLR3-targeting siRNA treatment. TLR3 agonist poly(I:C) promotes GAP-43 expression
      also in SK-N-AS cells only. Taken together, TLR3 could serve to predict favorable
      behavior in neuroblastomas. 

PMID- 23541684
TI  - Avastin and diode laser: a combined modality in managing epistaxis in hereditary
      hemorrhagic telangiectasia.
AB  - A patient with hereditary hemorrhagic telangiectasia is a rare presentation to
      the otolaryngologist in clinical practice. They almost present with epistaxis,
      which is recurrent, spontaneous and can be functionally and socially debilitating
      for the patient. Diode laser cauterization and Avastin intranasal injection
      showed significant improvement in epistaxis severity score. We report a case of
      hereditary hemorrhagic telangiectasia with chronic epistaxis (hemoglobin 3.4
      mg/dl) managed with Diode laser and intranasal Avastin injection with great
      improvement in life quality and decrease in epistaxis attacks. Despite all
      treatment options absolute eradication of epistaxis attacks is difficult to
      obtain in these cases.

PMID- 23541685
TI  - Saccadic velocity as an arousal index in naturalistic tasks.
AB  - Experimental evidence indicates that saccadic metrics vary with task difficulty
      and time-on-task in naturalistic scenarios. We explore historical and recent
      findings on the correlation of saccadic velocity with task parameters in
      clinical, military, and everyday situations, and its potential role in
      ergonomics. We moreover discuss the hypothesis that changes in saccadic velocity
      indicate variations in sympathetic nervous system activation; that is, variations
      in arousal.

PMID- 23541686
TI  - Development of a standardized ELISA for the determination of autoantibodies
      against human M-type phospholipase A2 receptor in primary membranous nephropathy.
AB  - BACKGROUND: Autoantibodies against the M-type phospholipase A2 receptor (PLA2R1)
      are specific markers for primary membranous nephropathy (pMN) and anti-PLA2R1
      serum levels may be useful to monitor disease activity. So far, a recombinant
      cell-based indirect immunofluorescence assay (RC-IFA) using recombinant PLA2R1 as
      a substrate has been widely available but lacks a finely graduated assessment of
      antibody concentrations. METHODS: In order to setup a standardized ELISA, the
      extracellular domain of human PLA2R1 was expressed in HEK293. The purified
      protein was used to form the solid-phase in an ELISA which was then employed to
      analyze sera from 200 patients with primary MN, 27 patients with secondary MN,
      230 patients with other glomerular diseases, 316 patients with systemic
      autoimmune diseases, and from 291 healthy blood donors. RESULTS: At a set
      specificity of 99.9% the sensitivity of the anti-PLA2R1 IgG ELISA was found to be
      96.5%. A similar sensitivity (98.5%) was obtained when binding of only subclass
      IgG4 was analyzed. The calibrated assay showed a good class correlation with the
      results of the RC-IFA, was robust and could be stored for several months without
      any loss of quality. CONCLUSION: The results demonstrate that the new test system
      is qualified for routine use and that it has an almost perfect agreement with
      both, the clinical characterization of the patients and the results generated
      with RC-IFA.

PMID- 23541687
TI  - A patient with limb girdle muscular dystrophy carries a TRIM32 deletion, detected
      by a novel CGH array, in compound heterozygosis with a nonsense mutation.
AB  - Limb girdle muscular dystrophy 2H is a rare autosomal recessive muscular
      dystrophy, clinically highly variable, caused by mutations in the TRIM32 gene.
      Here we describe a 35-years-old who experienced progressive muscle weakness. The
      muscle biopsy revealed an unspecific pattern of atrophic and hypertrophic fibers;
      the immunohistochemistry for several proteins was normal. Comparative genomic
      hybridization (CGH) analysis showed a heterozygous deletion of the entire TRIM32
      gene. On the other allele we identified the R316X nonsense mutation. The genetic
      diagnosis of LGMD2H in this case was reached by using a novel high throughput
      diagnostic tool.

PMID- 23541688
TI  - Genetic diversity and antibiotic resistance in Escherichia coli from
      environmental surface water in Dhaka City, Bangladesh.
AB  - The extended-spectrum beta-lactamase gene bla(CTX-M-15) was almost ubiquitous in
      diverse antibiotic-resistant Escherichia coli isolated from surface water around
      Dhaka City, Bangladesh. Forty-eight isolates represented 34 multi-locus sequence
      types and a variety of plasmid replicons were identified in association with
      bla(CTX-M-15) and other resistance genes. This water is likely to be an important
      source of transmissible antibiotic resistance in Bangladesh.

PMID- 23541689
TI  - A novel metallo-beta-lactamase, IMP-34, in Klebsiella isolates with decreased
      resistance to imipenem.
AB  - We investigated 5 metallo-beta-lactamase (MBL)-positive Klebsiella isolates from
      Japan showing intermediate resistance to imipenem. Sequencing of the MBL gene
      identified a novel variant of IMP-1 with a single amino acid substitution,
      Glu87Gly. This variant is designated as IMP-34 where blaIMP-34 is located on a
      transmissible plasmid.

PMID- 23541690
TI  - Comparison of antibiograms developed for inpatients and primary care outpatients.
AB  - To support antimicrobial stewardship, some healthcare systems have begun creating
      outpatient antibiograms. We developed inpatient and primary care outpatient
      antibiograms for a regional health maintenance organization (HMO) and academic
      healthcare system (AHS). Antimicrobial susceptibilities from 16,428 Enterococcus,
      Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa cultures from 2010 were summarized and compared. Methicillin
      susceptibility among S. aureus was similar in inpatients and primary care
      outpatients (HMO: 61.2% versus 61.9%, P = 0.951; AHS: 62.9% versus 63.3%, P >
      0.999). E. coli susceptibility to trimethoprim/sulfamethoxazole was also similar
      (HMO: 81.8% versus 83.6%, P = 0.328; AHS: 77.2% versus 80.9%, P = 0.192), but
      ciprofloxacin susceptibility differed (HMO: 88.9% versus 94.6%, P < 0.001; AHS:
      81.2% versus 90.6%, P < 0.001). In the HMO, ciprofloxacin-susceptible P.
      aeruginosa were more frequent in primary care outpatients than in inpatients
      (91.4% versus 79.0%, P = 0.007). Comparison of cumulative susceptibilities across
      settings yielded no consistent patterns; therefore, outpatient primary care
      antibiograms may more accurately inform prudent empiric antibiotic prescribing.

PMID- 23541692
TI  - Linezolid in late-chronic prosthetic joint infection caused by gram-positive
      bacteria.
AB  - Linezolid may be an interesting alternative for prosthetic joint infection (PJI)
      due to its bioavailability and its antimicrobial spectrum. However, experience in
      this setting is scarce. The aim of the study was to assess linezolid's clinical
      and microbiological efficacy, and also its tolerance. This was a prospective,
      multicenter, open-label, non-comparative study of 25 patients with late-chronic
      PJI caused by Gram-positive bacteria managed with a two-step exchange procedure
      plus 6 weeks of linezolid. Twenty-two (88%) patients tolerated linezolid without
      major adverse effects, although a global decrease in the platelet count was
      observed. Three patients were withdrawn because of major toxicity, which reversed
      after linezolid stoppage. Among patients who completed treatment, 19 (86%)
      demonstrated clinical and microbiological cure. Two patients presented with
      clinical and microbiological failure, and one showed clinical cure and
      microbiological failure. In conclusion, linezolid showed good results in chronic
      PJI managed with a two-step exchange procedure. Tolerance seems acceptable,
      though close surveillance is required.

PMID- 23541691
TI  - Quantitative determinations of anti-Kaposi sarcoma-associated herpesvirus
      antibody levels in men who have sex with men.
AB  - Infection with Kaposi sarcoma-associated herpesvirus (KSHV; also called human
      herpesvirus-8) is common among men who have sex with men (MSM). Here,
      quantitative anti-KSHV antibody levels were measured using luciferase
      immunoprecipitation systems (LIPS) in an MSM cohort with and without HIV from the
      NIH Clinical Center. Antibodies were detected using a mixture of 4 KSHV antigens
      in the MSM cohort and in Kaposi sarcoma (KS) patients. Along with HIV status,
      these results were compared with K8.1 and ORF73 ELISA, PCR virus detection, and
      additional LIPS testing. LIPS revealed that 25% (76/307) of the MSM cohort were
      KSHV seropositive, including 59 HIV+ and 17 HIV- subjects. The anti-KSHV antibody
      levels detected by LIPS were not statistically different between the KSHV+/HIV+
      and KSHV+/HIV- subgroups but were lower than the KS patients (P < 0.0001). ELISA
      analysis of the MSM cohort detected a 35.5% frequency of KSHV infection and
      showed agreement with 81% of the samples evaluated by LIPS. Further LIPS testing
      with v-cyclin, a second ORF73 fragment and ORF38 reconciled some of the
      differences observed between LIPS and the ELISA immunoassays, and the revised
      LIPS seroprevalence in the MSM cohort was increased to 31%. Additional
      quantitative antibody analysis demonstrated statistically lower KSHV antibody
      levels in MSM compared to KS patients, but no difference was found between KSHV
      infected with and without HIV coinfection. These findings also suggest that
      antibodies against v-cyclin and ORF38 are useful for identifying patients with
      asymptomatic KSHV infection.

PMID- 23541693
TI  - Functional analysis-make or break for cancer predictability.
AB  - Copy number variations (CNVs) encompass a variety of genetic alterations
      including deletions and amplifications and cluster in regions of the human genome
      with intrinsic instability. Small-sized CNVs can act as initial genetic changes
      giving rise to larger CNVs such as acquired somatic copy number aberrations
      (CNAs) promoting cancer formation. Previous studies provided evidence for CNVs as
      an underlying cause of elevated breast cancer risk when targeting breast cancer
      susceptibility genes and of accelerated breast cancer progression when targeting
      oncogenes. With the development of novel techniques for genome-wide detection of
      CNVs at increasingly higher resolution, it became possible to qualitatively and
      quantitatively analyse manifestation of DNA damage resulting from defects in any
      of the large variety of DNA double-strand break (DSB) repair mechanisms. Breast
      carcinogenesis, particularly in familial cases, has been linked with a defect in
      the homologous recombination (HR) pathway, which in turn switches damage removal
      towards alternative, more error-prone DSB repair pathways such as microhomology
      mediated non-homologous end joining (mmNHEJ). Indeed, increased error-prone DSB
      repair activities were detected in peripheral blood lymphocytes from individuals
      with familial breast cancer risk independently of specific gene mutations.
      Intriguingly, sequence analysis of breakpoint regions revealed that the majority
      of genome aberrations found in breast cancer specimens are formed by mmNHEJ.
      Detection of pathway-specific error-prone DSB repair activities by functional
      testing was proposed to serve as biomarker for hereditary breast cancer risk and
      responsiveness to therapies targeting HR dysfunction. Identification of specific
      error-prone DSB repair mechanisms underlying CNAs and ultimately mammary tumour
      formation highlights potential targets for future breast cancer prevention
      regimens.

PMID- 23541694
TI  - Synthesis of teicoplanin-modified hybrid magnetic mesoporous silica nanoparticles
      and their application in chiral separation of racemic compounds.
AB  - Teicoplanin-conjugated mesoporous silica magnetic nanoparticles (TE-MSMNPs) were
      fabricated as novel chiral magnetic nano-selectors. Successful preparation of the
      functional magnetic mesoporous materials was achieved by grafting teicoplanin on
      N-(2-aminoethyl)-3-aminopropyltrimethoxysilane-modified mesoporous silica Fe3O4
      magnetic nanoparticles (AEAPTMS-MSMNPs), and this was confirmed by various
      characterization techniques. The synthesized magnetic nanoparticles were
      regularly spherical and uniformly mesoporous with an average diameter of around
      600 nm and a mean pore size of about 3.9 nm, respectively. These versatile
      magnetic nanoparticles were effective in a direct chiral separation of five
      racemic compounds in phosphate buffer. Much stronger interactions were observed
      with the (+)-enantiomers than with the (-)-enantiomers. After washing with water
      and ethanol by sonication, TE-MSMNPs could be reused at least three times with
      little efficiency loss. The functional magnetic mesoporous nanoparticles were
      easily separated from the racemic solutions using an external magnetic field.
      These magnetic nano-materials are suitable for enantiomer separations.

PMID- 23541695
TI  - Host-guest complexes between cucurbit[n]urils and acetanilides having aminopropyl
      units.
AB  - 2-(Propylamino)acetamide of aniline (1a), and bis-2-(propylamino)acetamide of
      ortho- (1b) and para-(1c) phenylenediamine form host-guest complexes with CB[6],
      CB[7] and CB[8] as evidenced by the variations in the (1)H NMR spectroscopy
      chemical shifts and observation in MALDI-TOF-MS and ESI-MS of ions at the
      corresponding mass. Binding constants for the 1:1 complexes were estimated from
      fluorescence titrations and were in the range 10(5)-10(6)M(-1). Models based on
      molecular mechanics for these supramolecular complexes are provided. In spite of
      the different geometries arising from the ortho- or para-substitution,
      phenylenediamides form complexes of similar strength in which the hydrophobic
      alkyl chains are accommodated inside the host cavity. Formation of these host
      guest complexes in the solid state was also achieved by modifying an aminopropyl
      silica with chloroacetanilides and preparing three silica having analogues of
      compounds 1a-c anchored to the solid particles. Titrations showed, however, that
      these solids can adsorb a large percentage of CBs by unselective interactions
      that are not related to the formation of inclusion complexes.

PMID- 23541696
TI  - Bioimaging application of highly luminescent silica-coated ZnO-nanoparticle
      quantum dots with biotin.
AB  - We synthesized ZnO-nanoparticle quantum dots (QDs) as a fluorescent probe for
      biological applications. Highly luminescent silica-coated ZnO-nanoparticle QDs
      dispersed in an aqueous medium were synthesized using the sol-gel process. The
      ZnO-nanoparticle QDs were coated with silica to improve the water stability of
      the ZnO nanoparticles. NH2 groups were introduced on the surface of the silica
      coated ZnO-nanoparticle QDs first by the addition of 3
      aminopropyltrimethoxysilane and then by biotinylation with sulfosuccinimidyl-6
      (biotin-amido) hexanoate (sulfo-NHS-LC-bioton). We demonstrated that avidin
      immobilized agarose beads were tagged by the silica-coated ZnO-nanoparticle QDs
      with biotin by the selective avidin-biotin interaction, furnishing a fluorescent
      image upon excitation with UV light. Furthermore, use of the silica-coated ZnO
      nanoparticle QDs with biotin in cell-labeling applications was attempted, and
      attachment of the silica-coated ZnO-nanoparticle QDs with biotin to nerve cells
      and actin filaments was achieved.

PMID- 23541697
TI  - Preparative scale production and functional reconstitution of a human
      aquaglyceroporin (AQP3) using a cell free expression system.
AB  - Understanding the selectivity of aquaporin (AQP) membrane channels and exploiting
      their biotechnological potential will require structural and functional studies
      of wild type and modified proteins; however, expression systems have not
      previously yielded AQPs in the necessary milligrams quantities. Cell free (CF)
      systems have emerged in recent years as fast, efficient and versatile
      technologies for the production of high quality membrane proteins. Here, we
      establish a convenient method to synthesize large amounts of functional human
      aquaglyceroporin 3 protein (AQP3), an AQP of physiological relevance conducting
      glycerol and some small neutral solutes besides water. Milligram amounts of AQP3
      were produced as a histidine-tagged protein (hAQP3-6His) in an Escherichia coli
      extract-based CF system in the presence of the non-ionic detergent Brij-98. The
      recombinant AQP3 was purified by affinity chromatography, incorporated into
      liposomes and evaluated functionally by stopped-flow light scattering. Correct
      protein folding was indicated by the high glycerol and water permeability
      exhibited by the hAQP3-6His proteoliposomes as compared to empty control
      liposomes. Functionality of hAQP3-6His was further confirmed by the strong
      inhibition of the glycerol and water permeability by phloretin and HgCl2,
      respectively, two blockers of AQP3. Fast and convenient CF production of
      functional AQP3 may serve as basis for further structural/functional assessment
      of aquaglyceroporins and help boosting the AQP-based biomimetic technologies. 

PMID- 23541698
TI  - Hydrocarbonoclastic bacteria isolated from petroleum contaminated sites in
      Tunisia: isolation, identification and characterization of the biotechnological
      potential.
AB  - Petroleum hydrocarbons are important energy resources used by industry and in our
      daily life, whose production contributes highly to environmental pollution. To
      control such risk, bioremediation constitutes an environmentally friendly
      alternative technology that has been established and applied. It constitutes the
      primary mechanism for the elimination of hydrocarbons from contaminated sites by
      natural existing populations of microorganisms. In this work, a collection of 125
      strains, adapted to grow on minimal medium supplemented with crude oil, was
      obtained from contaminated sediments and seawater from a refinery harbor of the
      Bizerte coast in the North of Tunisia. The diversity of the bacterial collection
      was analyzed by amplification of the internal transcribed spacers between the 16S
      and the 23S rRNA genes (ITS-PCR) and by 16S rRNA sequencing. A total of 36
      distinct ITS haplotypes were detected on agarose matrix. Partial 16S rRNA gene
      sequencing performed on 50 isolates showed high level of identity with known
      sequences. Strains were affiliated to Ochrabactrum, Sphingobium, Acinetobacter,
      Gordonia, Microbacterium, Brevundimonas, Novosphingobium, Stenotrophomonas,
      Luteibacter, Rhodococcus, Agrobacterium, Achromobacter, Bacilllus, Kocuria and
      Pseudomonas genera. Acinetobacter and Stenotrophomons were found to be the most
      abundant species characterized by a marked microdiversity as shown through ITS
      typing. Culture-independent approach (DGGE) showed high diversity in the
      microbial community in all the studied samples with a clear correlation with the
      hydrocarbon pollution rate. Sequencing of the DGGE bands revealed a high
      proportion of Proteobacteria represented by the Alpha and Gamma subclasses. The
      predominant bacterial detected by both dependent and independent approaches were
      the Proteobacteria. The biotechnological potential of the isolates revealed a
      significant production of biosurfactants with important emulsification activities
      useful in bioremediation. The highest emulsification activity was detected in
      Pseudomonas geniculata with 52.77% of emulsification. Our overall results suggest
      that the obtained bacterial isolates may constitute potential candidates for
      bioremediation and can be useful for biotechnological applications.

PMID- 23541699
TI  - A novel bioactive peptide: assessing its activity over murine neural stem cells
      and its potential for neural tissue engineering.
AB  - The design of biomimetic scaffolds suitable for cell-based therapies is a
      fundamental step for the regeneration of the damaged nervous system; indeed
      growing interest is focusing on the discovery of peptide sequences to modulate
      the fate of transplanted cells and, in particular, the differentiation outcome of
      multipotent neural stem cells. By applying the Phage Display technique to murine
      neural stem cells we isolated a peptide, KLPGWSG, present in proteins involved in
      both stem cell maintenance and differentiation. We show that KLPGWSG binds
      molecules expressed on the cell surface of murine adult neural stem cells, thus
      may potentially be involved in stem cell fate determination. Indeed we
      demonstrated that this peptide in solution enhances per se cell differentiation
      toward the neuronal phenotype. Hence, we synthesized two LDLK-12-based self
      assembling peptides functionalized with KLPGWSG peptide (KLP and Ac-KLP) and
      characterized them via atomic force microscopy, rheometry and circular dichroism,
      obtaining nanostructured hydrogels supporting murine neural stem cells
      differentiation in vitro. Interestingly, we demonstrated that, when scaffold
      stiffness is comparable to that of the brain in vivo, the Ac-KLP SAP-based
      scaffold enhances the neuronal differentiation of neural stem cells. These
      evidences place both KLPGWSG and the functionalized self-assembling peptide Ac
      KLP as promising candidates for, respectively, biomimetic studies and stem cell
      therapies for nervous regeneration. 

PMID- 23541700
TI  - Trailing behind: limitations on transcatheter aortic valve implantation in
      Portugal.

PMID- 23541701
TI  - Indentation damage and crack repair in human enamel.
AB  - Tooth enamel is the hardest and most highly mineralized tissue in the human body.
      While there have been a number of studies aimed at understanding the hardness and
      crack growth resistance behavior of this tissue, no study has evaluated if cracks
      in this tissue undergo repair. In this investigation the crack repair
      characteristics of young human enamel were evaluated as a function of patient
      gender and as a function of the distance from the Dentin Enamel Junction (DEJ).
      Cracks were introduced via microindentation along the prism direction and
      evaluated as a function of time after the indentation. Microscopic observations
      indicated that the repair of cracks began immediately after crack initiation and
      reaches saturation after approximately 48 h. During this process he crack length
      decreased up to 10% of the initial length, and the largest degree of reduction
      occurred in the deep enamel, nearest the DEJ. In addition, it was found that the
      degree of repair was significantly greater in the enamel of female patients.

PMID- 23541702
TI  - Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune
      myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2
      cytokines.
AB  - Conventional therapies for autoimmune diseases produce nonspecific immune
      suppression, which are usually continued lifelong to maintain disease control,
      and associated with a variety of adverse effects. In this study, we found that
      spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune
      myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin
      in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13
      post immunization (p.i.) resulted in improved clinical symptoms, which were
      associated with increased numbers of CD4(+)CD25(+) T regulatory (Treg) cells and
      Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear
      cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines,
      decreased level of anti-R97-116 peptide (region 97-116 of the rat acetylcholine
      receptor alpha subunit) IgG antibody in serum. These tolerogenic DCs can migrate
      to spleen, thymus, popliteal and inguinal lymph nodes after they were injected
      into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played
      their immunomodulatory effects in vivo mainly by decreased expression of CD86 and
      MHC class II on endogenous DCs. All these data provided us a new strategy to
      treat EAMG and even human myasthenia gravis (MG). 

PMID- 23541703
TI  - Intramolecular regulation of presynaptic scaffold protein SYD-2/liprin-alpha.
AB  - SYD-2/liprin-alpha is a multi-domain protein that associates with and recruits
      multiple active zone molecules to form presynaptic specializations. Given SYD-2's
      critical role in synapse formation, its synaptogenic ability is likely tightly
      regulated. However, mechanisms that regulate SYD-2 function are poorly
      understood. In this study, we provide evidence that SYD-2's function may be
      regulated by interactions between its coiled-coil (CC) domains and sterile alpha
      motif (SAM) domains. We show that the N-terminal CC domains are necessary and
      sufficient to assemble functional synapses while C-terminal SAM domains are not,
      suggesting that the CC domains are responsible for the synaptogenic activity of
      SYD-2. Surprisingly, syd-2 alleles with single amino acid mutations in the SAM
      domain show strong loss of function phenotypes, suggesting that SAM domains also
      play an important role in SYD-2's function. A previously characterized syd-2 gain
      of-function mutation within the CC domains is epistatic to the loss-of-function
      mutations in the SAM domain. In addition, yeast two-hybrid analysis showed
      interactions between the CC and SAM domains. Thus, the data is consistent with a
      model where the SAM domains regulate the CC domain-dependent synaptogenic
      activity of SYD-2. Taken together, our study provides new mechanistic insights
      into how SYD-2's activity may be modulated to regulate synapse formation during
      development. 

PMID- 23541704
TI  - [Morbidity and mortality in pancreatic resection].
AB  - AIM: Assess the postoperative morbidity rates in pancreatic resection. MATERIAL
      AND METHOD: Prospective observational study which includes 117 patients who
      underwent surgery consecutively due to pancreatic or periampullary tumours. In 61
      of the patients, cephalic pancreatectomy was carried out; 15 underwent total
      pancreatectomy; one underwent enucleation and 40 underwent distal pancreatectomy.
      RESULTS: Overall morbidity was 48.7% (59% for cephalic pancreatectomy, 35% for
      distal pancreatectomy and 46.7% for total pancreatectomy). The most frequent
      complications were intra-abdominal abscesses and collections (15.38%) and medical
      complications (13.68%). The incidence of pancreatic fistula was 9.83% for
      cephalic pancreatectomy and 10% for distal pancreatectomy. The reintervention
      incidence was 14.53%. Overall mortality was 5.12% (6.56% for cephalic
      pancreatectomy, 2.5% for distal pancreatectomy and 6.67% for total
      pancreatectomy). The presence of postoperative complications, the need for
      reintervention and the fact of being over 70 years of age correlated
      significantly with mortality. DISCUSSION: Pancreatic resection has high morbidity
      rates. Mortality is low and is practically limited to patients older than 70
      years.

PMID- 23541705
TI  - [Parastomal hernia prevention through laparoscopic modified Sugarbaker technique
      with composite mesh (Physiomesh(r))].
AB  - The high incidence of parastomal hernia and the controversy surrounding its
      repair make its prevention an area of intense research. The aim of this article
      is to describe the modified Sugarbaker technique with a new mesh for the
      prevention of parastomal hernia using a laparoscopic approach.

PMID- 23541706
TI  - Utility and work productivity data for economic evaluation of breast cancer
      therapies in the Netherlands and Sweden.
AB  - OBJECTIVE: This study aimed to estimate utility values in laypeople and
      productivity loss for women with breast cancer in Sweden and the Netherlands.
      METHODS: To capture utilities, validated health state vignettes were used, which
      were translated into Dutch and Swedish. They described progressive disease,
      stable disease, and 7 grade 3/4 adverse events. One hundred members of the
      general public in each country rated the states using the visual analog scale and
      time trade-off method. To assess productivity, women who had recently completed
      or were currently receiving treatment for early or advanced breast cancer (the
      Netherlands, n = 161; Sweden, n = 52) completed the Work Productivity and
      Activity Impairment-General Health (WPAI-GH) questionnaire. Data were analyzed
      using means (SD). RESULTS: The utility study showed that the Swedish sample rated
      progressive and stable disease (mean, 0.61 [0.07] and 0.81 [0.05], respectively)
      higher than did the Dutch sample (0.49 [0.06] and 0.69 [0.05]). The health states
      incorporating the toxicities in both countries produced similar mean scores.
      Results of the WPAI-GH showed that those currently receiving treatment reported
      productivity reductions of 69% (the Netherlands) and 72% (Sweden); those who had
      recently completed therapy reported reductions of 41% (the Netherlands) and 40%
      (Sweden). CONCLUSIONS: The differences in the utility scores between the 2
      countries underline the importance of capturing country-specific values. The
      significant impact of adverse events on health-related quality of life was also
      highlighted. The WPAI-GH results demonstrated how the negative impact of breast
      cancer on productivity persists after women have completed their treatment.

PMID- 23541707
TI  - Patient-level medication regimen complexity across populations with chronic
      disease.
AB  - BACKGROUND: Expected treatment effectiveness from medications can be diminished
      due to suboptimal adherence. Medication nonadherence has been linked to pill
      burden from the quantity of medications; however, medication regimens with
      similar quantities of medications vary in complexity due to multiple dosage
      forms, frequency of dosing, and additional usage directions. Thus, a simple
      medication count ignores medication regimen complexity, especially as it pertains
      to a patient-level perspective that includes prescription and over-the-counter
      medications. A gap exists in the study of a patient-level medication regimen
      complexity metric across disease-specific populations. OBJECTIVE: The goal of
      this study was to implement the quantitative Medication Regimen Complexity Index
      (MRCI) at the patient level in defined populations with chronic disease
      (geriatric depression, HIV, diabetes mellitus, and hypertension). Patient-level
      medication regimen complexity included all prescribed medications and over-the
      counter medications documented in the electronic medication list. METHODS: Using
      electronic medical records at the University of Colorado Hospital ambulatory
      clinics, we sampled 4 retrospective cohorts of adult patients in active care in
      2011 with a qualifying medical diagnosis and prescribed disease-specific
      medication. Samples were randomly selected from all qualifying patients; de
      identified information was coded using the MRCI. RESULTS: Cohort-defining disease
      specific prescription medications (eg, antidepressants for the depression-defined
      cohort) contributed <20% to the total patient-level complexity MRCI score; the
      MRCI score was dominated by complexity associated with all other prescription
      medications. Within disease-specific cohorts, MRCI scores differentiated patients
      with the highest and lowest medication counts, comorbidity counts, and the
      Charlson comorbidity index scores. For example, geriatric depression patients had
      a highest quartile mean MRCI score of 41 and a lowest quartile mean MRCI score of
      13. Between disease-specific cohorts, high and low MRCI scores differed because
      each cohort had its own MRCI ranges. For example, highest quartile MRCI scores
      varied from a mean MRCI score of 41 (geriatric depression) to 30 (hypertension);
      lowest quartile scores ranged from a mean MRCI score of 7 (hypertension and HIV)
      to 13 (geriatric depression). CONCLUSIONS: MRCI components of dosing frequency
      and prescribed medications outside of the cohort-defining disease medications
      contributed the most to the patient-level scores. Thus, chronic disease
      management programs may want to consider all medications that patients are taking
      and examine ways to reduce complexity, such as reducing multiple dosing
      frequencies when possible. MRCI scores differentiated high and low patient-level
      complexity measures, representing possible utility as a prospective tool to
      identify target patients for intervention. Future work includes simplifying the
      MRCI and enhancing the scores with medication risk factors, as well as explicitly
      linking to adherence and health services.

PMID- 23541708
TI  - Relationship between pain relief and improvements in patient function/quality of
      life in patients with painful diabetic peripheral neuropathy or postherpetic
      neuralgia treated with pregabalin.
AB  - BACKGROUND: In patients with chronic pain due to diabetic peripheral neuropathy
      (DPN) or postherpetic neuralgia (PHN), pregabalin treatment results in pain
      relief and improved patient function/quality of life (QoL). Few studies, however,
      have examined the exact relationship between pain relief and improvements in
      patient function/QoL. It is unclear, for example, whether pregabalin has a direct
      independent effect on patient function/QoL or whether improvements in
      function/QoL are an indirect consequent of pain relief. OBJECTIVES: To determine
      whether improvements in function/QoL in response to pregabalin treatment are
      related to the extent of pain relief in patients with neuropathic pain due to DPN
      or PHN and to determine whether pregabalin has a direct independent effect on
      patient function/QoL that is distinct from its effects on pain. METHODS: Data
      from 11 randomized, double-blind, placebo-controlled trials of pregabalin for the
      treatment of DPN or PHN were pooled for this analysis. Changes in patient
      function/QoL scores were plotted according to the extent of pain relief to assess
      whether greater levels of pain relief were associated with greater improvement in
      function/QoL. A novel mediation analysis was used to asses to what extent the
      effects of pregabalin on function/QoL scores are a direct treatment effect as
      opposed to an indirect effect mediated through improvements in pain or sleep.
      RESULTS: Moderate-to-substantial pain relief (a >=30% decrease in pain) in
      response to pregabalin treatment was associated with significant (P < 0.05)
      improvements in 36-Item Short Form Health Survey (SF-36) scores (used to assess
      patient function/QoL). In many patients, greatest improvement in SF-36 scores was
      reported by patients achieving >=50% decrease in pain. Analysis of Patient Global
      Impression of Change scores revealed a similar trend, where >80% of patients who
      achieved substantial pain relief also reported their status as much or very much
      improved. A substantial direct pregabalin treatment effect was evident for many
      SF-36 domains that could not be explained by pain relief or improvement in sleep.
      CONCLUSIONS: In patients with chronic pain due to DPN or PHN, improvements in
      patient function/QoL in response to pregabalin treatment are correlated with the
      extent of pain relief. However, such improvements in function/QoL are not
      mediated entirely through pain relief but are the result of a combination of
      pregabalin's effects on pain and sleep disturbance and a direct effect on patient
      function itself.

PMID- 23541709
TI  - Patient-reported outcomes: current perspectives and future directions.

PMID- 23541710
TI  - Medicare Part D research highlights and policy updates, 2013: impact and
      insights.
AB  - BACKGROUND: Since its implementation in 2006, Medicare Part D has evolved from a
      program that offered basic access to covered drugs for beneficiaries to one that
      has the potential to affect patient outcomes. OBJECTIVES: The purpose of this
      article was to highlight key research findings on Medicare Part D published in
      2012 and major public policy initiatives for Part D for 2013. METHODS:
      PubMed/MEDLINE was searched for research studies on Part D published in 2012 in
      biomedical/scientific, peer-reviewed, English-language journals. For policy
      updates, sources included the Federal Register, the 2013 Final Call Letter,
      guidance from the Centers for Medicare and Medicaid Services, and 2012
      publications on Part D policy identified in PubMed. RESULTS: Part D has been
      associated with higher medication use and lower out-of-pocket (OOP) costs of many
      long-term medications; however, differences within subgroups of beneficiaries
      have been observed. Studies on health outcomes have been inconclusive. Part D
      policy changes in 2013 have addressed problems with the benefit, namely coverage
      of benzodiazepines and barbiturates; reducing coinsurance in the coverage gap;
      reducing fraud, waste, and abuse; medication therapy management program
      standardization; and an expanded appeals process. CONCLUSIONS: Research continues
      to suggest that Part D is effective in increasing medication utilization and
      lowering OOP costs. Further work is needed to clarify the effects of Part D on
      nondrug health care service utilization and health outcomes. Policy changes for
      2013 addressed specific improvements in the Medicare Part D benefit while
      potentially generating cost-savings for Medicare and Medicaid. Future challenges
      include alleviating access burden to medications during the phase-out of the
      coverage gap, minimizing disparities among Part D beneficiaries, and coordinating
      the Part D benefit with Medicare parts A and B via Medicare Accountable Care
      Organizations. A more integrated and coordinated Medicare benefit among all of
      its components would benefit overall health outcomes and increase cost-savings.

PMID- 23541711
TI  - Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and
      zolpidem oral immediate-release tablet: results from a single-center, single
      dose, randomized, open-label crossover study in healthy adults.
AB  - BACKGROUND: A zolpidem sublingual tablet (ZST) formulation was recently approved
      by the US Food and Drug Administration to treat middle-of-the-night (MOTN)
      awakening with difficulty returning to sleep. OBJECTIVE: The aim of this study
      was to compare the zolpidem pharmacokinetic profiles of 3.5-mg ZST and 10-mg
      immediate-release (IR) oral zolpidem in healthy female and male adults. METHODS:
      This randomized, open-label crossover study compared the pharmacokinetic profile
      of ZST with that of IR oral zolpidem in healthy adults. RESULTS: The study
      enrolled 19 males and 14 females. After 3.5-mg ZST and 10-mg IR, respectively,
      mean zolpidem plasma concentrations at 15 minutes (22 vs 17 ng/mL, respectively,
      in females and 18 vs 10 ng/mL in males) and AUCs from zero to 15 minutes (2.3 vs
      0.8 ng . h/mL in females and 1.6 vs 0.5 ng . h/mL in males) were substantially
      greater for ZST, despite the larger absolute IR dose. After 3.5-mg ZST and 10-mg
      IR, respectively, clearance was lower in females, even after correcting for body
      weight (2.63 vs 2.88 mL/min/kg in females and 3.63 vs 3.91 mL/min/kg in males).
      The lag time prior to the start of first-order absorption was notably shorter for
      ZST than IR in both males (8 vs 21 minutes) and females (5 vs 22 minutes). Both
      zolpidem formulations were generally well tolerated by both genders. CONCLUSIONS:
      Systemic exposure of zolpidem was higher in females for both formulations. Plasma
      levels and AUC were higher, and clearance was lower, in females with both
      zolpidem formulations. The initial rate of absorption was faster, and initial
      systemic exposure was greater, with ZST compared with oral IR.

PMID- 23541712
TI  - Linear accelerator: a reproducible, efficacious and cost effective alternative
      for blood irradiation.
AB  - BACKGROUND: The dedicated devices for blood irradiation are available only at a
      few centers in developing countries thus the irradiation remains a service with
      limited availability due to prohibitive cost. OBJECTIVE: To implement a blood
      irradiation program at our center using linear accelerator. MATERIALS AND
      METHODS: The study is performed detailing the specific operational and quality
      assurance measures employed in providing a blood component-irradiation service at
      tertiary care hospital. X-rays generated from linear accelerator were used to
      irradiate the blood components. To facilitate and standardize the blood component
      irradiation, a blood irradiator box was designed and fabricated in acrylic. Using
      Elekta Precise Linear Accelerator, a dose of 25 Gy was delivered at the centre of
      the irradiation box. Standardization was done using five units of blood obtained
      from healthy voluntary blood donors. Each unit was divided to two parts. One
      aliquot was subjected to irradiation. Biochemical and hematological parameters
      were analyzed on various days of storage. Cost incurred was analyzed. RESULTS:
      Progressive increase in plasma hemoglobin, potassium and lactate dehydrogenase
      was noted in the irradiated units but all the parameters were within the
      acceptable range indicating the suitability of the product for transfusion. The
      irradiation process was completed in less than 30 min. Validation of the
      radiation dose done using TLD showed less than +/- 3% variation. CONCLUSION: This
      study shows that that the blood component irradiation is within the scope of most
      of the hospitals in developing countries even in the absence of dedicated blood
      irradiators at affordable cost.

PMID- 23541713
TI  - CCK-8S increased the filopodia and spines density in cultured hippocampal neurons
      of APP/PS1 and wild-type mice.
AB  - Cholecystokinin (CCK), a neuropeptide, is widely distributed in the brain. The
      function of CCK is involved in many brain functions including learning and
      memory, but the cellular mechanism is poorly understood. In the present study, we
      investigated the effect of CCK on dendritic filopodia and spines of cultured
      hippocampal neurons from wild-type and APP/PS1 mice. The cultured hippocampal
      neurons were infected with CMV-GFP (CMV promoter with green fluorescent protein)
      adenovirus 24h before image acquisition to display the subtle structure of
      dendrites. Cholecystokinin octapeptide sulfated (CCK-8S, 0.2MUM) was added into
      the cultured solution from divided in vitro day 2 (DIV 2). A decrease of
      filopodia and spines density was observed in APP/PS1 mice compared with that of
      wild type mice. CCK-8S increased the density of filopodia and spines at DIV 7,
      DIV 14 and DIV 21 in hippocampal neurons of both wild-type and APP/PS1 mice. In
      addition, this effect was inhibited by CI988, an antagonist of CCK-2 receptor.
      Those results indicate that CCK-8S can influence the dendritic development and
      spine genesis of cultured hippocampal neurons derived from both wild-type and
      APP/PS1 mice. These data suggest that CCK may play an important role in learning
      and memory.

PMID- 23541714
TI  - Practice-based child health nursing research networks.

PMID- 23541715
TI  - Quantitative cross-linking/mass spectrometry using isotope-labelled cross
      linkers.
AB  - Dynamic proteins and multi-protein complexes govern most biological processes.
      Cross-linking/mass spectrometry (CLMS) is increasingly successful in providing
      residue-resolution data on static proteinaceous structures. Here we investigate
      the technical feasibility of recording dynamic processes using isotope-labelling
      for quantitation. We cross-linked human serum albumin (HSA) with the readily
      available cross-linker BS3-d0/4 in different heavy/light ratios. We found two
      limitations. First, isotope labelling reduced the number of identified cross
      links. This is in line with similar findings when identifying proteins. Second,
      standard quantitative proteomics software was not suitable for work with cross
      linking. To ameliorate this we wrote a basic open source application, XiQ. Using
      XiQ we could establish that quantitative CLMS was technically feasible.
      BIOLOGICAL SIGNIFICANCE: Cross-linking/mass spectrometry (CLMS) has become a
      powerful tool for providing residue-resolution data on static proteinaceous
      structures. Adding quantitation to CLMS will extend its ability of recording
      dynamic processes. Here we introduce a cross-linking specific quantitation
      strategy by using isotope labelled cross-linkers. Using a model system, we
      demonstrate the principle and feasibility of quantifying cross-linking data and
      discuss challenges one may encounter while doing so. We then provide a basic open
      source application, XiQ, to carry out automated quantitation of CLMS data. Our
      work lays the foundations of studying the molecular details of biological
      processes at greater ease than this could be done so far.

PMID- 23541716
TI  - Comparative proteomics, network analysis and post-translational modification
      identification reveal differential profiles of plasma Con A-bound glycoprotein
      biomarkers in gastric cancer.
AB  - In the study, we used Con A affinity chromatography, 1-D gel electrophoresis, and
      nano-LC-MS/MS to screen biomarker candidates in plasma samples obtained from 30
      patients with gastric cancer and 30 healthy volunteers. First, we pooled plasma
      samples matched by age and sex. We identified 17 differentially expressed Con A
      bound glycoproteins, including 10 upregulated proteins and 7 downregulated
      proteins; these differences were significant (Student's t-test, p-value<0.05).
      Furthermore, 2 of the upregulated proteins displayed expression levels that were
      increased by 2-fold or more in gastric cancer samples when compared with normal
      control samples. These proteins included leucine-rich alpha-2-glycoprotein (LRG1)
      and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), and the expression
      levels were validated by Western blot analysis. Pathway and network analysis of
      the differentially expressed proteins by Ingenuity Pathway Analysis revealed
      vital canonical pathways involving acute phase response signaling, the complement
      system, LXR/RXR activation, hematopoiesis from pluripotent stem cells, and
      primary immunodeficiency signaling. Our results suggest that Con A-bound LRG1 and
      ITIH3 may not be practically applicable as a robust biomarker for the early
      detection of gastric cancer. Additionally, three novel PTMs in ITIH3 were
      identified and include hexose-N-acetyl-hexosamine at asparagine-(41),
      trimethylation at aspartic acid-(290), and flavin adenine dinucleotide at
      histidine-(335). BIOLOGICAL SIGNIFICANCE: Our study was to describe a
      combinatorial approach of Con A affinity chromatography, 1-D SDS-PAGE, and nano
      LC/MS/MS that provides a label-free, comparative glycoproteomic quantification
      strategy for the investigation of glycoprotein profiles in plasma from gastric
      cancer patients versus healthy volunteers and to identify glycoprotein biomarkers
      for the early clinical detection of gastric cancer. Three novel PTMs, HexHexNAc,
      trimethylation and FAD, in Con A-bound ITIH3 were identified and built in
      molecular modeling. The aspartic acid-(290) trimethylation site was located in a
      metal ion-dependent adhesion site (MIDAS motif; (290)-DXSXS...T...D-(313)) that
      may influence important function for binding protein ligands.

PMID- 23541717
TI  - Composite indices of femoral neck strength in adult female soccer players.

PMID- 23541718
TI  - The prevalence of aortic calcification on vertebral fracture assessment imaging
      among patients with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are at increased risk of osteoporosis
      (OP) and cardiovascular disease (CVD). Dual-energy X-ray absorptiometry scans
      have been validated for identifying patients with RA at risk for fracture.
      Reliable CVD risk stratification remains an unmet need in this population.
      Vertebral fracture assessment (VFA)-detected abdominal aortic calcification (AAC)
      has been validated as a marker of CVD in other populations, but the prevalence
      among patients with RA is unknown. In this study, we determined the prevalence
      and severity of AAC on VFA scans in a cohort of patients with RA. AAC was
      detected in 211 of the 603 (35%) eligible subjects; 24% were graded as severe. In
      multivariable analyses, the presence of AAC was significantly associated with
      longer disease duration and higher disease activity (p<0.05). Further studies are
      needed on the relationship between AAC and CVD in patients with RA. 

PMID- 23541719
TI  - Role of serotonin in zebrafish (Danio rerio) anxiety: relationship with serotonin
      levels and effect of buspirone, WAY 100635, SB 224289, fluoxetine and para
      chlorophenylalanine (pCPA) in two behavioral models.
AB  - Serotonin (5-HT) is a neurotransmitter that is involved in many behavioral
      functions, including the organization of defense, and its putative pathological
      correlate, anxiety and stress disorders. Recently, behavioral tests for anxiety
      have been proposed in zebrafish. Exposure to the novel tank test or to the
      light/dark test increased extracellular fluid 5-HT content in the brain; anxiety
      like behavior correlated positively with 5-HT content in the novel tank test,
      while the correlation was negative in the light/dark test. Acute treatment with a
      low dose of fluoxetine was anxiolytic in the geotaxis test and anxiogenic in the
      scototaxis test, while treatment with a higher dose produced a hyperlocomotor
      effect in both tasks. Buspirone and WAY 100635 were anxiolytic in both tests,
      while SB 224289 was anxiolytic in the geotaxis and slightly anxiogenic in the
      scototaxis test. Serotonin depletion with pCPA was anxiogenic in the geotaxis and
      anxiolytic in scototaxis. These results underline the differential sensitivity of
      these tasks to assess serotonergic agents; alternatively, serotonin might
      regulate zebrafish behavior differently in the novel tank test and in the
      light/dark test.

PMID- 23541721
TI  - Tuning into diversity of homeostatic synaptic plasticity.
AB  - Neurons are endowed with the remarkable ability to integrate activity levels over
      time and tune their excitability such that action potential firing is maintained
      within a computationally optimal range. These feedback mechanisms, collectively
      referred to as "homeostatic plasticity", enable neurons to respond and adapt to
      prolonged alterations in neuronal activity by regulating several determinants of
      cellular excitability. Perhaps the best-characterized of these homeostatic
      responses involves the regulation of excitatory glutamatergic transmission. This
      homeostatic synaptic plasticity (HSP) operates bidirectionally, thus providing a
      means for neurons to tune cellular excitability in response to either elevations
      or reductions in net activity. The last decade has seen rapid growth in interest
      and efforts to understand the mechanistic underpinnings of HSP in part because of
      the theoretical stabilization that HSP confers to neural network function. Since
      the initial reports describing HSP in central neurons, innovations in
      experimental approaches have permitted the mechanistic dissection of this
      cellular adaptive response and, as a result, key advances have been made in our
      understanding of the cellular and molecular basis of HSP. Here, we review recent
      evidence that outline the presence of distinct forms of HSP at excitatory
      glutamatergic synapses which operate at different sub-cellular levels. We further
      present theoretical considerations on the potential computational roles afforded
      by local, synapse-specific homeostatic regulation. This article is part of the
      Special Issue entitled 'Homeostatic Synaptic Plasticity'. 

PMID- 23541720
TI  - The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats.
AB  - Nitric oxide modulates pain development. However, there is no evidence on the
      effect of nitroxyl (HNO/NO-) in nociception. Therefore, we addressed whether
      nitroxyl inhibits inflammatory hyperalgesia and its mechanism using the nitroxyl
      donor Angeli's salt (AS; Na2N2O3). Mechanical hyperalgesia was evaluated using a
      modified Randall and Selitto method in rats, cytokine production by ELISA and
      nitroxyl was determined by confocal microscopy in DAF (a cell permeable reagent
      that is converted into a fluorescent molecule by nitrogen oxides)-treated dorsal
      root ganglia neurons in culture. Local pre-treatment with AS (17-450 MUg/paw, 30
      min) inhibited the carrageenin-induced mechanical hyperalgesia in a dose- and
      time-dependent manner with maximum inhibition of 97%. AS also inhibited
      carrageenin-induced cytokine production. AS inhibited the hyperalgesia induced by
      other inflammatory stimuli including lipopolysaccharide, tumor necrosis factor
      alpha, interleukin-1beta and prostaglandin E2. Furthermore, the analgesic effect
      of AS was prevented by treatment with ODQ (a soluble guanylate cyclase
      inhibitor), KT5823 (a protein kinase G [PKG] inhibitor) or glybenclamide (an ATP
      sensitive K+ channel blocker), but not with naloxone (an opioid receptor
      antagonist). AS induced concentration-dependent increase in fluorescence
      intensity of DAF-treated neurons in a l-cysteine (nitroxyl scavenger) sensitive
      manner. l-cysteine did not affect the NO+ donor S-Nitroso-N-acetyl-DL-
      penicillamine (SNAP)-induced anti-hyperalgesia or fluorescence of DAF-treated
      neurons. This is the first study to demonstrate that nitroxyl inhibits
      inflammatory hyperalgesia by reducing cytokine production and activating the
      cGMP/PKG/ATP-sensitive K+ channel signaling pathway in vivo.

PMID- 23541722
TI  - The multitarget opioid ligand LP1's effects in persistent pain and in primary
      cell neuronal cultures.
AB  - Persistent pain states, such as those caused by nerve injury or inflammation, are
      associated with altered sensations, allodynia and hyperalgesia, that are
      resistant to traditional analgesics. A contribution to development and
      maintenance in altered pain perception comes from nociceptive processing and
      descending modulation from supraspinal sites. A multitarget ligand seems to be
      useful for pain relief with a decreased risk of adverse events and a considerable
      analgesic efficacy. The multitarget MOR agonist-DOR antagonist LP1, (3
      [(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benazocin
      3(2H)-yl]-N-phenylpropanamide, is a central acting antinociceptive agent with low
      potential to induce tolerance. LP1 was tested in models of neuropathic pain -
      induced by chronic constriction injury (CCI) of the left sciatic nerve - and
      inflammatory pain - produced by intraplantar injection of carrageenan. In CCI
      rats, subcutaneous (s.c.) LP1 (3 mg/kg) showed a significant antiallodynic
      effect, measured with von Frey filaments, and antihyperalgesic effect, evoked in
      response to a radiant heat stimulus with plantar test. Analogously, LP1
      significantly reduced allodynic and hyperalgesic thresholds in a model of
      inflammatory pain induced by carrageenan. To evaluate the contribution of opioid
      receptor subtypes in LP1 antinociceptive effects, the multitarget LP1 profile was
      assessed using selective opioid antagonists. Moreover, functional
      electrophysiological in vitro assays, using primary cortical and spinal cord
      networks, allowed to define the "pharmacological fingerprint" of LP1. The EC50
      values in this functional screening seem to confirm LP1 as a potent opioid ligand
      (EC50 = 0.35 fM and EC50 = 44 pM in spinal cord and frontal cortex,
      respectively). Using a NeuroProof data-base of well characterised reference
      compounds, a similarity profile of LP1 to opioid and non-opioid drugs involved in
      pain modulation was detected. Our studies seem to support that multitarget ligand
      approach should be useful for persistent pain conditions in which mechanical
      allodynia and thermal hyperalgesia are significant components of the nociceptive
      response.

PMID- 23541723
TI  - Valproic acid attenuates ischemia-reperfusion injury in the rat brain through
      inhibition of oxidative stress and inflammation.
AB  - Valproic acid (VPA), widely used in clinical contexts for the treatment of
      seizures and bipolar mood disorder, has neuroprotective properties in cellular
      and animal models. However, the precise mechanisms underlying its neuroprotection
      against stroke remain unknown. In the present study, we explored the effect of
      VPA on experimental ischemic stroke. Male Sprague-Dawley rats were subjected to
      middle cerebral artery occlusion for 90 min, followed by reperfusion. The animals
      received a single injection of VPA (300 mg/kg) immediately, 90, or 270 min after
      the induction of ischemia. Vehicle-treated animals underwent the same procedure
      with physiological saline. Infarct volume and neurological symptoms were
      evaluated 24 h after reperfusion. Immunohistochemical staining for
      myeloperoxidase (MPO), microglia (Iba1), 4-hydroxy-2-nonenal (4-HNE), or 8
      hydroxy-deoxyguanosine (8-OHdG) was performed. Ischemic boundary zone cell death
      was determined by TUNEL staining. VPA injected immediately or 90 min after
      ischemia induction significantly reduced infarct volume and improved neurological
      deficit compared with vehicle (P<0.05). VPA was ineffective when given 270 min
      after ischemia induction. VPA significantly reduced TUNEL-positive cells, MPO
      positive cells, Iba1-positive cells, 4-HNE-positive cells, and 8-OHdG-positive
      cells compared with vehicle in the ischemic boundary zone (P<0.05). The
      therapeutic time window for single injection of VPA is between 0 and 90 min in
      this model. Our results demonstrate that single injection of VPA may have anti
      inflammatory as well as antioxidative effects, leading to reduced cell death in
      ischemia-reperfusion injury.

PMID- 23541724
TI  - Relevance of the cyclophosphamide-induced cystitis model for pharmacological
      studies targeting inflammation and pain of the bladder.
AB  - This work aimed at establishing the relevance of using the in vivo model of
      cyclophosphamide (CYP)-induced bladder inflammation in rats for in vivo
      pharmacological studies. Specifically, we measured visceral nociception,
      identified key inflammatory mediators and evaluated the effects of relevant
      pharmacological treatments. Cystitis was induced in female rats by a single CYP
      injection. Sensitivity of the lower abdomen to von Frey mechanical stimulation
      was determined as a nociceptive parameter. Bladders were assessed for weight,
      wall thickness and macroscopic damage. Inflammatory mediators were quantified in
      bladders and urines. The effects of aspirin, ibuprofen and morphine were
      investigated on all these parameters. A single CYP injection increased
      nociceptive scores and decreased nociceptive threshold in response to mechanical
      stimuli between 1 and 4h post-administration. Increased bladder weight and wall
      thickness were associated with edema and hemorrhage. Bladder levels of IL-1beta,
      IL-6, MCP-1 and VCAM, and urinary levels of PGE2 were increased. In contrast, a
      decrease in the urinary metabolites, indoxyl sulfate and pantothenic acid, was
      observed. Aspirin, ibuprofen and morphine decreased CYP-induced referred visceral
      pain. Aspirin and ibuprofen also reversed the increased wall thickness,
      macroscopic damage and levels of IL-1beta, IL-6 and PGE2, and the decreased
      panthotenic acid levels. In contrast, morphine increased wall thickness, edema,
      hemorrhage, and bladder IL-6 and MCP-1 levels. This work presents a new and
      reliable method to evaluate visceral sensitivity in rats, and new relevant
      biomarkers identified in the bladder and urine to measure inflammation and pain
      parameters for in vivo pharmacological studies.

PMID- 23541725
TI  - BF-30 selectively inhibits melanoma cell proliferation via cytoplasmic membrane
      permeabilization and DNA-binding in vitro and in B16F10-bearing mice.
AB  - Cathelicidin-BF (BF-30) is a cathelicidin-like polypeptide composed of 30 amino
      acids and is a natural antibacterial peptide extracted from the venom of the
      snake Bungarus fasciatus. In our previous study, BF-30 showed broad antimicrobial
      activity against drug-resistant bacteria through enhancing the cytoplasmic
      membrane permeability. However, the anticancer activity of BF-30 has not yet been
      investigated. In this study, the effects of BF-30 on the proliferation of the
      metastatic melanoma cell line B16F10 in vitro and in vivo, as well as the
      mechanism were studied. Assay of cell viability, a B16F10-bearing mouse model,
      and histochemical examination were utilized to investigate the anti-tumor effects
      of BF-30. In addition, transmission electron microscope analysis, lactate
      dehydrogenase release assay, DNA retardation assay, Real-time PCR, Western blot,
      wound healing assay, and chick embryo chorioallantoic membrane assay were applied
      to elucidate the mechanism of BF-30 on B16F10. BF-30 inhibited B16F10 and B16
      proliferation in vitro in a dose- and time-dependent manner with an IC50 of 7.3
      uM and 13.9 uM, respectively. Moreover, BF-30 significantly suppressed melanoma
      growth in B16F10-bearing mice without body weight loss. The observed inhibition
      were 41.4%, 49.5% and 63.5% at the doses of 0.75, 1.5 and 3 mg/kg/day,
      respectively. This inhibition of metastatic melanoma cell proliferation was
      partially dependent on disrupting the cytoplasmic membrane, binding to genomic
      DNA, preventing transcription and translation of the VEGF gene. This inhibition
      restrained B16F10 migration and angiogenesis. These results further suggest that
      BF-30 may be a candidate for the treatment of malignant melanoma.

PMID- 23541726
TI  - Keratocyte fragments and cells utilize competing pathways to move in opposite
      directions in an electric field.
AB  - Sensing of an electric field (EF) by cells-galvanotaxis-is important in wound
      healing [1], development [2], cell division, nerve growth, and angiogenesis [3].
      Different cell types migrate in opposite directions in EFs [4], and the same cell
      can switch the directionality depending on conditions [5]. A tug-of-war mechanism
      between multiple signaling pathways [6] can direct Dictyostelium cells to either
      cathode or anode. Mechanics of motility is simplest in fish keratocytes, so we
      turned to keratocytes to investigate their migration in EFs. Keratocytes sense
      electric fields and migrate to the cathode [7, 8]. Keratocyte fragments [9, 10]
      are the simplest motile units. Cell fragments from leukocytes are able to respond
      to chemotactic signals [11], but whether cell fragments are galvanotactic was
      unknown. We found that keratocyte fragments are the smallest motile electric
      field-sensing unit: they migrate to the anode, in the opposite direction of whole
      cells. Myosin II was essential for the direction sensing of fragments but not for
      parental cells, while PI3 kinase was essential for the direction sensing of whole
      cells but not for fragments. Thus, two signal transduction pathways, one
      depending on PI3K, another on myosin, compete to orient motile cells in the
      electric field. Galvanotaxis is not due to EF force and does not depend on cell
      or fragment size. We propose a "compass" model according to which protrusive and
      contractile actomyosin networks self-polarize to the front and rear of the motile
      cell, respectively, and the electric signal orients both networks toward cathode
      with different strengths.

PMID- 23541727
TI  - Vervet monkeys solve a multiplayer "forbidden circle game" by queuing to learn
      restraint.
AB  - In social dilemmas, the ability of individuals to coordinate their actions is
      crucial to reach group optima. Unless exacted by power or force, coordination in
      humans relies on a common understanding of the problem, which is greatly
      facilitated by communication. The lack of means of consultation about the nature
      of the problem and how to solve it may explain why multiagent coordination in
      nonhuman vertebrates has commonly been observed only when multiple individuals
      react instantaneously to a single stimulus, either natural or experimentally
      simulated, for example a predator, a prey, or a neighboring group. Here we report
      how vervet monkeys solved an experimentally induced coordination problem. In each
      of three groups, we trained a low-ranking female, the "provider," to open a
      container holding a large amount of food, which the providers only opened when
      all individuals dominant to them ("dominants") stayed outside an imaginary
      "forbidden circle" around it. Without any human guidance, the dominants learned
      restraint one by one, in hierarchical order from high to low. Once all dominants
      showed restraint immediately at the start of the trial, the providers opened the
      container almost instantly, saving all individuals opportunity costs due to lost
      foraging time. Solving this game required trial-and-error learning based on
      individual feedback from the provider to each dominant, and all dominants being
      patient enough to wait outside the circle while others learned restraint.
      Communication, social learning, and policing by high-ranking animals played no
      perceptible role.

PMID- 23541728
TI  - Dispersal of grouper larvae drives local resource sharing in a coral reef
      fishery.
AB  - In many tropical nations, fisheries management requires a community-based
      approach because small customary marine tenure areas define the spatial scale of
      management [1]. However, the fate of larvae originating from a community's tenure
      is unknown, and thus the degree to which a community can expect their management
      actions to replenish the fisheries within their tenure is unclear [2, 3].
      Furthermore, whether and how much larval dispersal links tenure areas can provide
      a strong basis for cooperative management [4, 5]. Using genetic parentage
      analysis, we measured larval dispersal from a single, managed spawning
      aggregation of squaretail coral grouper (Plectropomus areolatus) and determined
      its contribution to fisheries replenishment within five community tenure areas up
      to 33 km from the aggregation at Manus Island, Papua New Guinea. Within the
      community tenure area containing the aggregation, 17%-25% of juveniles were
      produced by the aggregation. In four adjacent tenure areas, 6%-17% of juveniles
      were from the aggregation. Larval dispersal kernels predict that 50% of larvae
      settled within 14 km of the aggregation. These results strongly suggest that both
      local and cooperative management actions can provide fisheries benefits to
      communities over small spatial scales.

PMID- 23541729
TI  - Systematic analysis of neural projections reveals clonal composition of the
      Drosophila brain.
AB  - BACKGROUND: During development neurons are generated by sequential divisions of
      neural stem cells, or neuroblasts. In the insect brain progeny of certain stem
      cells form lineage-specific sets of projections that arborize in distinct brain
      regions, called clonal units. Though this raises the possibility that the entire
      neural network in the brain might be organized in a clone-dependent fashion, only
      a small portion of clones has been identified. RESULTS: Using Drosophila
      melanogaster, we randomly labeled one of about 100 stem cells at the beginning of
      the larval stage, analyzed the projection patterns of their progeny in the adult,
      and identified 96 clonal units in the central part of the fly brain, the
      cerebrum. Neurons of all the clones arborize in distinct regions of the brain,
      though many clones feature heterogeneous groups of neurons in terms of their
      projection patterns and neurotransmitters. Arborizations of clones overlap
      preferentially to form several groups of closely associated clones. Fascicles and
      commissures were all made by unique sets of clones. Whereas well-investigated
      brain regions such as the mushroom body and central complex consist of relatively
      small numbers of clones and are specifically connected with a limited number of
      neuropils, seemingly disorganized neuropils surrounding them are composed by a
      much larger number of clones and have extensive specific connections with many
      other neuropils. CONCLUSIONS: Our study showed that the insect brain is formed by
      a composition of cell-lineage-dependent modules. Clonal analysis reveals
      organized architecture even in those neuropils without obvious structural
      landmarks.

PMID- 23541730
TI  - Nonsynaptic plasticity underlies a compartmentalized increase in synaptic
      efficacy after classical conditioning.
AB  - It is now well documented in both vertebrates and invertebrates that nonsynaptic
      as well as synaptic plasticity can be a substrate for long-term memory [1-4].
      Little is known, however, about how learning-induced nonsynaptic plasticity can
      lead to compartmentalized presynaptic changes underlying specific memory traces
      while leaving other circuit functions of the neuron unaffected. Here, using
      behavioral, electrophysiological, and optical recording methods, we show that the
      previously described learning-induced depolarization of a modulatory neuron [5]
      of the Lymnaea feeding system affects its axonal terminals in a spatially
      segregated manner. In a side branch of the axon of the cerebral giant cells
      (CGCs), classical conditioning of intact animals reduced proximal-to-distal
      attenuation of spike-evoked calcium transients, providing a highly effective
      mechanism for a compartmentalized increase in synaptic efficacy. Somatic
      depolarization by current injection, which spreads onto the CGC's axonal side
      branch [5], and the blocking of A-type potassium channels with 4-aminopyridine
      had an effect similar to learning on the calcium transients. Both of these
      experimental manipulations also reduced axonal spike attenuation. These findings
      suggest that the voltage-dependent inactivation of an A-type potassium current
      links global nonsynaptic changes to compartmentalized synaptic changes.

PMID- 23541731
TI  - Electrophoresis of cellular membrane components creates the directional cue
      guiding keratocyte galvanotaxis.
AB  - BACKGROUND: Motile cells exposed to an external direct current electric field
      will reorient and migrate along the direction of the electric potential in a
      process known as galvanotaxis. The underlying physical mechanism that allows a
      cell to sense an electric field is unknown, although several plausible hypotheses
      have been proposed. In this work we evaluate the validity of each of these
      mechanisms. RESULTS: We find that the directional motile response of fish
      epidermal cells to the cathode in an electric field does not require
      extracellular sodium or potassium, is insensitive to membrane potential, and is
      also insensitive to perturbation of calcium, sodium, hydrogen, or chloride ion
      transport across the plasma membrane. Cells migrate in the direction of applied
      forces from laminar fluid flow, but reversal of electro-osmotic flow did not
      affect the galvanotactic response. Galvanotaxis fails when extracellular pH is
      below 6, suggesting that the effective charge of membrane components might be a
      crucial factor. Slowing the migration of membrane components with an increase in
      aqueous viscosity slows the kinetics of the galvanotactic response. In addition,
      inhibition of PI3K reverses the cell's response to the anode, suggesting the
      existence of multiple signaling pathways downstream of the galvanotactic signal.
      CONCLUSIONS: Our results are most consistent with the hypothesis that
      electrophoretic redistribution of membrane components of the motile cell is the
      primary physical mechanism for motile cells to sense an electric field. This
      chemical polarization of the cellular membrane is then transduced by
      intracellular signaling pathways canonical to chemotaxis to dictate the cell's
      direction of travel.

PMID- 23541732
TI  - A synthetic gene drive system for local, reversible modification and suppression
      of insect populations.
AB  - Replacement of wild insect populations with genetically modified individuals
      unable to transmit disease provides a self-perpetuating method of disease
      prevention but requires a gene drive mechanism to spread these traits to high
      frequency. Drive mechanisms requiring that transgenes exceed a threshold
      frequency in order to spread are attractive because they bring about local but
      not global replacement, and transgenes can be eliminated through dilution of the
      population with wild-type individuals. These features are likely to be important
      in many social and regulatory contexts. Here we describe the first creation of a
      synthetic threshold-dependent gene drive system, designated maternal-effect
      lethal underdominance (UD(MEL)), in which two maternally expressed toxins,
      located on separate chromosomes, are each linked with a zygotic antidote able to
      rescue maternal-effect lethality of the other toxin. We demonstrate threshold
      dependent replacement in single- and two-locus configurations in Drosophila.
      Models suggest that transgene spread can often be limited to local environments.
      They also show that in a population in which single-locus UD(MEL) has been
      carried out, repeated release of wild-type males can result in population
      suppression, a novel method of genetic population manipulation.

PMID- 23541734
TI  - The use of adjuvant endocrine breast cancer therapy in the oldest old.
AB  - In order to report specifically on the use of adjuvant endocrine therapy (ET) in
      the oldest old breast cancer (BC) patients, we compared treatment patterns
      including drug compliance and persistence in a cohort of patients who were >= 80
      years at diagnosis (n = 79) with those of "younger elderly" patients who were 60
      79 years old (n = 358). The geriatric cohort more commonly declined the
      recommended ET (non-compliance: 13.0% vs. 4.5%, p = 0.011). Of the patients who
      initiated ET, only a minority of the older patients completed the planned therapy
      duration of five years (39.6% vs. 71.3%, p < 0.001). However, when applying
      strict criteria for non-persistence, this was found in comparable frequency
      (17.0% vs. 12.0%, p = 0.370). In older patients, medication was more often
      discontinued by the physician due to serious medical reasons independent of BC
      (17.0% vs. 4.7%, p = 0.003). Older women were treated by a general practitioner
      more often and not by an oncologist (54.4% vs. 23.9%, p < 0.001). Studies on
      compliance/persistence on cancer therapy in the oldest old demand a detailed
      follow-up of the patients and the consideration of principles of geriatric
      medicine. Efforts should be made to make sure that all physicians, but above all
      general practitioners, who are predominantly involved in the treatment of elderly
      BC patients, are provided with current knowledge and skills, as to ensure optimal
      patient management.

PMID- 23541735
TI  - A simple and fast method for tissue cryohomogenization enabling multifarious
      molecular extraction.
AB  - Research in molecular biology often relies on parallel analysis of nucleic acids,
      protein and other molecules from a given tissue. When extracted from a single
      sample however, the quality and quantity of these products can be compromised.
      One solution is to obtain near-identical samples from multiple animals and
      dedicate each to a given molecular component, but this approach is not optimal
      from both an operational and ethical perspective. Thus, we refined the methods
      for cryohomogenization to allow efficient use of a single experimental sample so
      that it can easily be divided into fractions for extraction of different
      molecular components, immediately or after storage. Using western blot, nanodrop
      UV/V spectrometry, and a bioanalyzer, we show that cryohomogenized hippocampus
      samples provide high-quality RNA and protein without significant loss in
      abundance. The method may be particularly advantageous for parallel molecular
      extraction from brain structures with known hemispheric lateralization, such as
      the hippocampus, parietal cortex, suprachiasmatic nucleus, and amygdala.

PMID- 23541736
TI  - WITHDRAWN: Neural circuits with long-distance axon tracts for determining
      functional connectivity.
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- 23541733
TI  - Clonal development and organization of the adult Drosophila central brain.
AB  - BACKGROUND: The insect brain can be divided into neuropils that are formed by
      neurites of both local and remote origin. The complexity of the interconnections
      obscures how these neuropils are established and interconnected through
      development. The Drosophila central brain develops from a fixed number of
      neuroblasts (NBs) that deposit neurons in regional clusters. RESULTS: By
      determining individual NB clones and pursuing their projections into specific
      neuropils, we unravel the regional development of the brain neural network.
      Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with
      characteristic cell-body locations and neurite trajectories. Most clones show
      complex projection patterns, but despite the complexity, neighboring clones often
      coinnervate the same local neuropil or neuropils and further target a restricted
      set of distant neuropils. CONCLUSIONS: These observations argue for regional
      clonal development of both neuropils and neuropil connectivity throughout the
      Drosophila central brain.

PMID- 23541737
TI  - Bridges and barriers to successful transitioning as perceived by adolescents and
      young adults with Asperger syndrome.
AB  - In this thematic content analysis we examined the expectations, and perceived
      facilitators of (referred to as bridges) and barriers to transition to community
      as reported by adolescents and young adults with Asperger syndrome. Participants
      were adolescents/young adults, ages 18-23 years were from the East Coast of the
      United States. Seventy percent of adolescents hoped for employment (n = 10).
      Thirty percent desired to find a partner and raise a family. Perceived barriers
      were: self-assessed behavioral problems, self-assessed associated features, other
      personal factors, and institutional factors. Bridges to facilitate transition
      were: accommodations in the community, cognitive abilities, personal
      qualities/strengths, and mentor's qualities.

PMID- 23541738
TI  - Relationship between health status, illness perceptions, coping strategies and
      psychological morbidity: a preliminary study with IBD stoma patients.
AB  - BACKGROUND AND AIMS: Individuals living with IBD and a stoma are at an increased
      risk of anxiety and depression and it is likely that several factors mediate
      these relationships, including illness perceptions and coping strategies. Using
      the Common Sense Model (CSM), this study aimed to characterize the mediators of
      anxiety and depression in an IBD stoma cohort. METHODS: Eighty-three adults (23
      males) with a stoma (25 ileostomy, 58 colostomy; 26 emergency, 57 planned, 55
      permanent, 28 temporary) completed an online survey. Health status was measured
      with the Health Orientation Scale (HOS), coping styles assessed with the Carver
      Brief COPE scale, illness perceptions explored with the Brief Illness Perceptions
      Questionnaire (BIPQ), and anxiety and depression were measured using the Hospital
      Anxiety and Depression Scale (HADS). RESULTS: Combining the questionnaire data
      using structural equation modeling resulted in a final model with an excellent
      fit (chi(2) (11)=12.86, p=0.30, chi(2)/N=1.17, SRMR<0.05, RMSEA<0.05, GFI>0.96,
      CFI>0.99). Consistent with the CSM, health status directly influenced illness
      perceptions, which in turn, influenced coping (emotion-focused and maladaptive
      coping). Interestingly, months since surgery was found to influence illness
      perceptions and emotion-focused coping directly, but not health status. While
      depression was influenced by illness perceptions, emotion-focused coping and
      maladaptive coping, anxiety was only influenced by illness perceptions and
      maladaptive coping. CONCLUSIONS: The preliminary results provide further evidence
      for the complex interplay between psychological processes. In terms of directions
      for psychological interventions, a focus on identifying and working with illness
      perceptions is important.

PMID- 23541739
TI  - Predicting long non-coding RNAs using RNA sequencing.
AB  - The advent of next-generation sequencing, and in particular RNA-sequencing (RNA
      seq), technologies has expanded our knowledge of the transcriptional capacity of
      human and other animal, genomes. In particular, recent RNA-seq studies have
      revealed that transcription is widespread across the mammalian genome, resulting
      in a large increase in the number of putative transcripts from both within, and
      intervening between, known protein-coding genes. Long transcripts that appear to
      lack protein-coding potential (long non-coding RNAs, lncRNAs) have been the focus
      of much recent research, in part owing to observations of their cell-type and
      developmental time-point restricted expression patterns. A variety of sequencing
      protocols are currently available for identifying lncRNAs including RNA
      polymerase II occupancy, chromatin state maps and - the focus of this review -
      deep RNA sequencing. In addition, there are numerous analytical methods available
      for mapping reads and assembling transcript models that predict the presence and
      structure of lncRNAs from RNA-seq data. Here we review current methods for
      identifying lncRNAs using large-scale sequencing data from RNA-seq experiments
      and highlight analytical considerations that are required when undertaking such
      projects.

PMID- 23541740
TI  - A survey of resident physicians' knowledge regarding urine testing and subsequent
      antimicrobial treatment.
AB  - BACKGROUND: Asymptomatic bacteriuria is often treated with antimicrobials despite
      no benefit to patients, contributing to antimicrobial resistance and costs.
      Identifying knowledge deficits may improve physician training and antimicrobial
      stewardship efforts. We surveyed internal medicine and medicine-pediatrics
      resident physicians about their knowledge and attitudes regarding urine testing
      and subsequent management. METHODS: We surveyed 280 resident physicians at
      Jackson Memorial Hospital/University of Miami Miller School of Medicine and the
      University of Minnesota Medical School, using patient management questions based
      on clinical vignettes. Overall knowledge, assessed by calculating the percentage
      of correct answers, was assessed for correlation with demographic information,
      training, and experience. RESULTS: Of 100 responses (36% response rate), the mean
      percentage of correct answers was 48% (range for individual questions, 19%-85%).
      Experience and demographic factors demonstrated no association with overall
      knowledge. Training appeared to be associated with overall knowledge, with third
      year residents having significantly higher percentages of correct answers
      compared with first-year residents (53% vs 40%; P = .03), but this was
      nonsignificant when adjusted for multiple comparisons (P = .18). Knowledge was
      significantly better for questions regarding surgical versus nonsurgical
      scenarios (63% vs 37%; P < .001), and for questions for which the correct answer
      was to start antimicrobials, versus withholding antimicrobials/limiting further
      testing (83% vs 39%; P < .001). CONCLUSIONS: Knowledge deficits may contribute to
      unnecessary detection and treatment of asymptomatic bacteriuria.

PMID- 23541741
TI  - Regional anesthesia approaches to pain management in pediatric palliative care: a
      review of current knowledge.
AB  - CONTEXT: Although systemic analgesic therapies are the mainstay of pain treatment
      in pediatric palliative care, there are cases where they fail to adequately
      relieve symptoms or produce side effects that undermine effectiveness. Regional
      anesthesia may be considered as a potential therapy for these patients.
      OBJECTIVES: To review the literature on regional techniques in pediatric patients
      with life-limiting and chronic conditions, including pain from tumor
      infiltration, chest pain in advanced pulmonary disease, chronic abdominal pain,
      phantom limb pain, and spasticity and dystonia. Where relevant, the authors'
      clinical experiences are included. METHODS: References were identified by
      searches of PubMed from 1980 until June 2012 with related terms. RESULTS: Case
      reports and case series were identified for each condition. Regional anesthesia
      techniques performed included central neuraxial infusions, peripheral nerve and
      plexus blocks or infusions, neurolytic blocks, and implanted intrathecal ports
      and pumps for baclofen, opioids, local anesthetics, and other adjuvants. The
      reports described positive contributions to the management of moderate-to-severe
      pain. Clinical context for these techniques frequently included the failure of
      systemic treatments and/or intolerable medication side effects. Complications
      varied according to the procedure and the underlying patient pathology; however,
      these risks were often acceptable when the potential benefits were consistent
      with the overall goals of care. CONCLUSION: The present medical literature on
      regional anesthesia techniques in children receiving palliative care is limited
      to case reports and case series. Based on this evidence, recommendations must be
      provisional. Careful thought and discussion with pain management specialists are
      encouraged when pain symptoms are inadequately managed or the treatments produce
      deleterious side effects.

PMID- 23541742
TI  - Low dopamine D5 receptor density in hippocampus in an animal model of attention
      deficit/hyperactivity disorder (ADHD).
AB  - A state of low dopaminergic activity has been implicated in attention
      deficit/hyperactivity disorder (ADHD). The clinical symptoms of ADHD include
      inattention, impulsivity and hyperactivity, as well as impaired learning;
      dopaminergic modulation of the functions in the hippocampus is important to both
      learning and memory. To determine dopamine receptor (DR) density in a well
      established animal model for ADHD, we quantified the dopamine D5 receptors in the
      hippocampus in the spontaneously hypertensive rat. We used immunofluorescence
      microscopy and immunogold electron microscopy to quantify the dopamine D5
      receptor density on CA1 pyramidal cell somas and dendrites and dendritic spines
      in the stratum radiatum and stratum oriens. The density of the dopamine D5
      receptors was significantly lower in the cytoplasm of pyramidal cell somas in the
      spontaneously hypertensive rat compared to the control, indicating a reduced
      reservoir for insertion of receptors into the plasma membrane. DRs are important
      for long-term potentiation and long-term depression, hence the deficit may
      contribute to the learning difficulties in individuals with the diagnosis of
      ADHD.

PMID- 23541743
TI  - The effect of curcumin on sepsis-induced acute lung injury in a rat model through
      the inhibition of the TGF-beta1/SMAD3 pathway.
AB  - Curcumin has the potential to treat inflammatory diseases. This study
      investigated its effect on sepsis-induced acute lung injury (ALI) in a rat model.
      125 healthy rats were randomly divided into five groups, including normal group,
      sham-operated group, sepsis group, dimethyl sulfoxide group, and curcumin-treated
      group (25 rats in each subgroup). Sepsis-induced acute lung injury was affected
      by cecal ligation and puncture surgery. At 0, 6, 12, 24, and 48 h after
      treatment, the lungs were harvested for histological and protein expression
      examinations. 24h after the initial treatment, real-time PCR and Western blot
      analysis showed that the expression of TGF-beta1 and SMAD3-dependent signaling
      pathway was significantly decreased in the curcumin-treated group than other
      control groups (P<0.05). Therefore, curcumin played a protective role in sepsis
      induced ALI, possibly through the inhibition of the expression of TGF-beta1/SMAD3
      pathway which may provide a new strategy for the treatment of sepsis-induced ALI.

PMID- 23541744
TI  - Cucurbitacin IIa induces caspase-3-dependent apoptosis and enhances autophagy in
      lipopolysaccharide-stimulated RAW 264.7 macrophages.
AB  - Cucurbitacin IIa (CuIIa), a member of cucurbitacin family, is isolated from the
      root of Hemsleya amabilis which has been used as an ancient remedy for bacillary
      dysentery and gastroenteritis. The anti-inflammatory properties of CuIIa have
      long been recognized but the underlying mechanism is largely unknown. In this
      study, we investigated the anti-inflammatory effect of CuIIa on
      lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results
      showed that CuIIa inhibited the proliferation and migration of RAW 264.7 cells in
      a dose-dependent manner. Whereas CuIIa did not cause apoptosis in unstimulated
      RAW 264.7 cells, it did induce a significant apoptosis in LPS-stimulated cells,
      which was caspase-3-dependent and associated with downregulation of survivin.
      Furthermore, LPS induced autophagy in RAW 264.7 cells and this effect was further
      enhanced by CuIIa as evidenced by increased levels of LC3-II conjugates and
      formation of LC3 puncta. In addition, CuIIa disrupted actin cytoskeleton via
      inducing actin aggregation. However, neither the synthesis of tumor necrosis
      factor-alpha, nor the activation of the mitogen-activated protein kinases and NF
      kappaB pathways in LPS-stimulated cells was suppressed by CuIIa treatment.
      Collectively, these results suggested that induction of apoptosis and enhancement
      of autophagy contributed to the anti-inflammatory activity of CuIIa against
      inflammation-related diseases.

PMID- 23541745
TI  - In silico modeling to predict drug-induced phospholipidosis.
AB  - Drug-induced phospholipidosis (DIPL) is a preclinical finding during
      pharmaceutical drug development that has implications on the course of drug
      development and regulatory safety review. A principal characteristic of drugs
      inducing DIPL is known to be a cationic amphiphilic structure. This provides
      evidence for a structure-based explanation and opportunity to analyze properties
      and structures of drugs with the histopathologic findings for DIPL. In previous
      work from the FDA, in silico quantitative structure-activity relationship (QSAR)
      modeling using machine learning approaches has shown promise with a large dataset
      of drugs but included unconfirmed data as well. In this study, we report the
      construction and validation of a battery of complementary in silico QSAR models
      using the FDA's updated database on phospholipidosis, new algorithms and
      predictive technologies, and in particular, we address high performance with a
      high-confidence dataset. The results of our modeling for DIPL include rigorous
      external validation tests showing 80-81% concordance. Furthermore, the predictive
      performance characteristics include models with high sensitivity and specificity,
      in most cases above >=80% leading to desired high negative and positive
      predictivity. These models are intended to be utilized for regulatory toxicology
      applied science needs in screening new drugs for DIPL.

PMID- 23541746
TI  - Cranial fistulae: venous occlusion, the road to cure and misery.

PMID- 23541747
TI  - Reopening closed highways for stroke prevention.

PMID- 23541748
TI  - Cerebral revascularization for skull base tumors.

PMID- 23541749
TI  - The application of indocyanine green videoangiography in the neurosurgery of
      vascular entities.

PMID- 23541750
TI  - Lumbar discectomy: many ways to skin a cat.

PMID- 23541751
TI  - An alternate viewing universe.

PMID- 23541752
TI  - Craniopharyngiomas: infradiaphragmatic and supradiaphragmatic type and their
      management in modern times.

PMID- 23541753
TI  - Shifting paradigms of endovascular therapies for cavernous carotid fistulas.

PMID- 23541754
TI  - The necessity of multimodality workup in cervical spine injury.

PMID- 23541755
TI  - Clival and craniovertebral junction chordomas.

PMID- 23541757
TI  - Antisense makes sense for amyotrophic lateral sclerosis.

PMID- 23541756
TI  - An antisense oligonucleotide against SOD1 delivered intrathecally for patients
      with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in
      man study.
AB  - BACKGROUND: Mutations in SOD1 cause 13% of familial amyotrophic lateral
      sclerosis. In the SOD1 Gly93Ala rat model of amyotrophic lateral sclerosis, the
      antisense oligonucleotide ISIS 333611 delivered to CSF decreased SOD1 mRNA and
      protein concentrations in spinal cord tissue and prolonged survival. We aimed to
      assess the safety, tolerability, and pharmacokinetics of ISIS 333611 after
      intrathecal administration in patients with SOD1-related familial amyotrophic
      lateral sclerosis. METHODS: In this randomised, placebo-controlled, phase 1
      trial, we delivered ISIS 333611 by intrathecal infusion using an external pump
      over 11.5 h at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, 3.00 mg) to four
      cohorts of eight patients with SOD1-positive amyotrophic lateral sclerosis (six
      patients assigned to ISIS 333611, two to placebo in each cohort). We did the
      randomisation with a web-based system, assigning patients in blocks of four.
      Patients and investigators were masked to treatment assignment. Participants were
      allowed to re-enrol in subsequent cohorts. Our primary objective was to assess
      the safety and tolerability of ISIS 333611. Assessments were done during infusion
      and over 28 days after infusion. This study was registered with
      Clinicaltrials.gov, number NCT01041222. FINDINGS: Seven of eight (88%) patients
      in the placebo group versus 20 of 24 (83%) in the ISIS 333611 group had adverse
      events. The most common events were post-lumbar puncture syndrome (3/8 [38%] vs
      8/24 [33%]), back pain (4/8 [50%] vs 4/24 [17%]), and nausea (0/8 [0%] vs 3/24
      [13%]). We recorded no dose-limiting toxic effects or any safety or tolerability
      concerns related to ISIS 333611. No serious adverse events occurred in patients
      given ISIS 333611. Re-enrolment and re-treatment were also well tolerated.
      INTERPRETATION: This trial is the first clinical study of intrathecal delivery of
      an antisense oligonucleotide. ISIS 333611 was well tolerated when administered as
      an intrathecal infusion. Antisense oligonucleotides delivered to the CNS might be
      a feasible treatment for neurological disorders. FUNDING: The ALS Association,
      Muscular Dystrophy Association, Isis Pharmaceuticals.

PMID- 23541758
TI  - Association of discoid lupus erythematosus with other clinical manifestations
      among patients with systemic lupus erythematosus.
AB  - BACKGROUND: Cutaneous discoid lupus erythematosus (DLE) among patients with
      systemic lupus erythematosus (SLE) may be associated with less severe disease and
      with low frequency of nephritis and end-stage renal disease (ESRD). OBJECTIVE: We
      sought to investigate associations between confirmed DLE and other SLE
      manifestations, adjusting for confounders. METHODS: We identified patients with
      rheumatologist confirmation, according to 1997 American College of Rheumatology
      (ACR) SLE classification criteria, more than 2 visits, longer than 3 months of
      follow-up, and documented year of SLE diagnosis. DLE was confirmed by a
      dermatologist, supported by histopathology and images. SLE manifestations,
      medications, and serologies were collected. Multivariable-adjusted logistic
      regression analyses tested for associations between DLE and each of the ACR SLE
      criteria, and ESRD. RESULTS: A total of 1043 patients with SLE (117 with DLE and
      926 without DLE) were included in the study. After multivariable adjustment, DLE
      in SLE was significantly associated with photosensitivity (odds ratio [OR] 1.63),
      leukopenia (OR 1.55), and anti-Smith antibodies (OR 2.41). DLE was significantly
      associated with reduced risks of arthritis (OR 0.49) and pleuritis (OR 0.56). We
      found no significant associations between DLE and nephritis or ESRD. LIMITATIONS:
      Cross-sectional data collection with risk of data not captured from visits
      outside system was a limitation. CONCLUSIONS: In our SLE cohort, DLE was
      confirmed by a dermatologist and we adjusted for possible confounding by
      medication use, in particular hydroxychloroquine. We found increased risks of
      photosensitivity, leukopenia, and anti-Smith antibodies and decreased risks of
      pleuritis and arthritis in patients with SLE and DLE. DLE was not related to anti
      double-stranded DNA antibodies, lupus nephritis, or ESRD. These findings have
      implications for prognosis among patients with SLE.

PMID- 23541759
TI  - Fingernail psoriasis reconsidered: a case-control study.
AB  - BACKGROUND: Literature concerning clinical signs and frequency of nail psoriasis
      is incomplete. Recent studies focus only on signs included in the Nail Psoriasis
      Severity Index (NAPSI). OBJECTIVE: We sought to describe clinical characteristics
      of fingernail psoriasis in comparison with healthy controls. METHODS: We
      collected data on 49 patients with fingernail psoriasis who visited our
      outpatient department and 49 control subjects, through questionnaires and
      clinical examination. The disease severity was measured by the NAPSI. RESULTS:
      Mean NAPSI score in patients and control subjects was 26.6 and 3.6, respectively.
      Most items included in the NAPSI were specific for nail psoriasis. Onycholysis
      and splinter hemorrhages were most frequently observed. Leukonychia was more
      frequent in control subjects. Longitudinal ridges and Beau lines are not included
      in the NAPSI but are significantly more frequently seen in patients than in
      control subjects. LIMITATIONS: Limited sample size was a limitation. CONCLUSION:
      The NAPSI was able to discriminate patients with fingernail psoriasis from
      healthy control subjects. Onycholysis and splinter hemorrhages were the most
      prevalent fingernail changes in psoriatic patients. Leukonychia was more
      frequently observed in control subjects, which raises the question of whether
      leukonychia should remain in the NAPSI. On the other hand, longitudinal ridges
      and Beau lines occurred more frequently in psoriasis but are not included in the
      NAPSI.

PMID- 23541760
TI  - Development and validation of a predictive model for nonadherence with once-daily
      glaucoma medications.
AB  - OBJECTIVE: To develop and validate a predictive model to estimate the probability
      of being nonadherent to topical glaucoma medications. DESIGN: Prospective cohort
      study. PARTICIPANTS: Patients being treated with once-daily prostaglandin eye
      drops. METHODS: A predictive model for nonadherence was developed from the
      Travatan Dosing Aid (TDA) study (n = 196) using stepwise logistic regression. The
      performance of the TDA-derived model was assessed using a separate cohort of
      subjects from the Automated Dosing Reminder Study (ADRS; n = 407). The assessment
      was based on regression coefficients, discrimination, and calibration. We also
      developed a scoring system from the TDA-derived model to simplify the estimation
      of risk for clinical use. MAIN OUTCOME MEASURES: Usage of drops was monitored
      electronically for 3 months in both studies. Adherence was calculated as the
      percentage of days on which a dose was taken within 4 hours of the average dosing
      time for that patient. Nonadherence was defined as taking <= 75% prescribed doses
      within a window starting 2 weeks after the baseline visit until 2 weeks before
      the follow-up visit. RESULTS: Six factors, including younger age, black race,
      worse general health status, shorter duration of glaucoma medication therapy,
      lower self-reported adherence, and admitting to not following doctors' orders,
      were associated with being nonadherent and were included in the predictive model.
      The coefficients for the TDA-derived and the ADRS-derived predictive models were
      similar. The risk scoring system developed from the TDA study had good
      discrimination (area under the receiver operating characteristic curve of 0.80)
      and calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.102) when applied to
      the ADRS population. CONCLUSIONS: The TDA-derived predictive model for
      nonadherence performed well in an independent population. A risk scoring system
      was developed using demographic data and patient responses to 4 questions to
      provide an estimate of the probability of being nonadherent.

PMID- 23541761
TI  - Ability of cirrus high-definition spectral-domain optical coherence tomography
      clock-hour, deviation, and thickness maps in detecting photographic retinal nerve
      fiber layer abnormalities.
AB  - PURPOSE: To investigate the ability of clock-hour, deviation, and thickness maps
      of Cirrus high-definition spectral-domain optical coherence tomography (HD-OCT)
      in detecting retinal nerve fiber layer (RNFL) defects identified in red-free
      fundus photographs in eyes with early glaucoma (mean deviation >-6.0 dB). DESIGN:
      Cross-sectional study. PARTICIPANTS: Two hundred ninety-five eyes with
      glaucomatous RNFL defects with clear margins observed in red-free fundus
      photographs and 200 age-, sex-, and refractive error-matched healthy eyes were
      enrolled. METHODS: The width and location of RNFL defects were evaluated by using
      the red-free fundus photograph. When a RNFL defect detected by red-free fundus
      photograph did not present as (1) yellow/red codes in the clock-hour map, (2)
      yellow/red pixels in the deviation map, or (3) blue/black areas in the thickness
      map, the event was classified as a misidentification of a photographic RNFL
      defect by Cirrus HD-OCT. In healthy eyes, the presence of false-positive RNFL
      color codes of Cirrus HD-OCT maps was investigated. MAIN OUTCOME MEASURES: The
      prevalence of and factors associated with the (1) misidentification of
      photographic RNFL defects by Cirrus HD-OCT in eyes with glaucoma and (2) false
      positive RNFL color codes of Cirrus HD-OCT maps in healthy eyes were assessed.
      RESULTS: Among the 295 red-free fundus photographic RNFL defects from 295 eyes
      with glaucoma, 83 (28.1%), 27 (9.2%), and 0 (0%) defects were misidentified in
      the clock-hour, deviation, and thickness maps of Cirrus HD-OCT, respectively.
      Fifty-six defects (19.0%) were misidentified only in the clock-hour map and 27
      (9.2%) in both the clock-hour and deviation maps. The misidentification of
      photographic RNFL defects by Cirrus HD-OCT was associated with a narrower width
      and a temporal location of RNFL defects (P<0.05). Among the 200 healthy eyes, 25
      (12.5%), 30 (15.0%), and 12 (6.0%) eyes had false-positive RNFL color codes in
      clock-hour, deviation, and thickness maps of Cirrus HD-OCT, respectively.
      CONCLUSIONS: Among the clock-hour, deviation, and thickness maps obtained with
      Cirrus HD-OCT, the thickness map showed the best diagnostic ability in detecting
      photographic RNFL defects. The RNFL thickness map may be a useful tool for the
      detection of RNFL defects in eyes with early glaucoma.

PMID- 23541762
TI  - Anatomic features and function of the macula and outcome of surgical tenotomy and
      reattachment in achiasma.
AB  - OBJECTIVE: To examine the anatomic features and function of the macula in
      achiasma and to compare visual acuity, eye movements, foveation, and eye velocity
      before and after tenotomy and reattachment (T&R) surgery. DESIGN: Case series.
      PARTICIPANTS: Two children with isolated achiasma. METHODS: Ophthalmologic
      examinations, brain magnetic resonance imaging, full-field and multifocal
      electroretinography (ERG), visual evoked potentials (VEPs), spectral-domain
      optical coherence tomography (OCT), eye-movement recordings, and unilateral T&R
      in 1 patient. MAIN OUTCOME MEASURES: Visual acuity before and after surgery,
      macular anatomic features and function, and eye velocity before and after T&R
      surgery in 1 patient. RESULTS: Magnetic resonance imaging and VEP confirmed
      absence of decussation of retinofugal fibers in both patients. Visual acuity was
      20/100 and 20/200. The anatomic features and function of the fovea and macula
      were normal by OCT and multifocal ERG. After T&R, there was a marked reduction in
      horizontal eye velocity and monocular visual acuity improved to 20/80.
      CONCLUSIONS: The finding that the macula is normal in achiasma suggests that
      reduced acuity is the result of retinal image motion from nystagmus. Two-muscle
      T&R reduces horizontal retinal image motion and can improve visual acuity in
      achiasma or patients with infantile nystagmus.

PMID- 23541763
TI  - Deregulated expression of urokinase and its inhibitor type 1 in prostate cancer
      cells: role of epigenetic mechanisms.
AB  - Plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen
      activator (uPA) play a crucial role in cancer progression. In the present study
      we examined the regulation of PAI-1 and uPA expressions in normal prostate
      epithelial cells (PrEC) and the prostate cancer cell lines LNCaP, DU-145, and PC
      3. The antigen and mRNA levels of PAI-1 were down-regulated in cancer cells,
      especially in LNCaP and DU-145. In the presence of proinflammatory cytokines, an
      increase of PAI-1 mRNA levels was observed in PrEC, LNCaP and PC-3, but not in DU
      145 cells. Treatment with demethylating agent, 5-aza-2'-deoxycytidine increased
      the level of PAI-1 transcript in DU-145 cells and restored the inducing effect of
      cytokines on PAI-1 expression. An aberrant methylation of PAI-1 promoter in DU
      145 and LNCaP cells was shown by methylation-sensitive high resolution melting
      (MS-HRM) analysis. PAI-1 methylation was also significantly increased in tumor
      samples (23.2+/-1.7%) in comparison to adjacent non-tumor tissue (6.0+/-0.8%).
      Furthermore, the expression of uPA was increased in high invasive cell lines DU
      145 and PC-3 in comparison to PrEC and low invasive LNCaP cells. MS-HRM analysis
      revealed aberrant methylation of uPA promoter in LNCaP cells, but not in PrEC, DU
      145 and PC-3 cells, as well as in normal and prostate cancer tissue samples. In
      conclusion, the study shows that PAI-1 and uPA expressions were changed in
      opposite directions in high invasive prostate cancer cell lines resulting in a
      strong decrease of PAI-1/uPA ratio, which may indicate a shift towards
      proteolytic activities. Methylation of the PAI-1 gene is suggested as one of the
      molecular mechanisms involved in the cancer-associated down-regulation of the PAI
      1 expression.

PMID- 23541764
TI  - Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation
      and overcome breast cancer treatment in an in vitro breast cancer model.
AB  - Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective
      Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal
      symptoms. Women often try to relieve these symptoms by taking menopausal
      supplements containing high levels of phytoestrogens. However, little is known
      about the potential interaction between these supplements and breast cancer
      treatment, especially aromatase inhibitors. In this study, interaction of
      phytoestrogens with the estrogen receptor alpha and TAM action was determined in
      an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor
      cells (MCF-7). Potential interactions with aromatase activity and LET were
      determined in human adrenocorticocarcinoma H295R cells. We also used the
      previously described H295R/MCF-7 co-culture model to study interactions with
      steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8
      prenylnaringenin (8PN) and four commercially available menopausal supplements all
      induced ER-dependent tumor cell proliferation, which could not be prevented by
      physiologically relevant LET and 4OH-TAM concentrations. Differences in relative
      effect potencies between the H295R/MCF-7 co-culture model and ER-activation in
      BG1Luc4E2 cells, were due to the effects of the phytoestrogens on
      steroidogenesis. All tested supplements and GEN induced aromatase activity, while
      8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN
      exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells
      and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that
      menopausal supplement intake during breast cancer treatment should better be
      avoided, at least until more certainty regarding the safety of supplemental use
      in breast cancer patients can be provided.

PMID- 23541765
TI  - Kinematic characteristics of the tibiofemoral joint during a step-up activity.
AB  - The step-up activity (stair-ascending) is an important daily function of the
      knee. This study aimed to investigate the articular cartilage contact kinematics
      on both tibial and femoral cartilage surfaces and describe the femoral condylar
      motion using the transepicondylar axis (TEA) and the geometric center axis (GCA)
      during a step-up activity. Twenty-one healthy subjects were included and their
      knee joint models were reconstructed using MR images. A single-stair step-up
      activity was imaged using a dual-fluoroscopic imaging system. Three-dimensional
      knee joint contact points were determined and projected onto the tibial plateau
      and femoral condylar surfaces. The contact points on the medial and lateral
      tibial plateau moved anteriorly (by 13.5+/-3.2 and 10.7+/-5.0 mm, respectively,
      p>0.05) with knee extension. The contact points on the medial and lateral femoral
      condyle moved from the posterior to the anterior portion (by 32.2+/-4.9 mm and
      25.5+/-4.2 mm, respectively, p<0.05) and were located on the inner half of the
      femoral cartilage throughout the activity. The data on articular contact
      kinematics and the femoral condylar motion described using the TEA and GCA
      indicated that the medial and lateral compartments had similar motion patterns
      during the step-up activity. The knee does not demonstrate a medial-pivoting
      motion character during the step-up activity. The data may provide insight to
      contemporary TKA development.

PMID- 23541766
TI  - Kinematic and kinetic analysis during forward and backward walking.
AB  - Backward walking (BW) is a recently emerging exercise. However, limited studies
      exist regarding the motion analysis of BW compared with that of forward walking
      (FW). The present study identified the mechanisms of BW through kinetic analysis
      and focused on BW time-reversed data. A three-dimensional motion capture system
      was used to acquire the joint movements and to calculate the joint moments and
      the powers during walking. Ground reaction force curves were acquired from force
      plates. Each participant performed 10 FW trials and 40 BW trials with bare feet.
      All data were analyzed using paired t-tests (p<0.05) to verify the significant
      differences between FW and BW. In BW, since the progress is in the direction in
      which the person cannot see, the walker's speed is generally decreased compared
      to FW. As a result, the stride characteristics for each respective activity
      showed significant differences. The characteristics of angular displacement in
      all joints were almost identical in FW and time-reversed BW. However, selected
      crucial points of joint angles were significantly different. The moment pattern
      of the ankle joint was very similar in FW and time-reversed BW. In the knee and
      the hip joint, the joint moment pattern of time-reversed BW was simpler than FW.
      The joint power patterns of the ankle, the knee and the hip were different in FW
      and BW. An original finding of this study was that the main propulsion and shock
      absorption joint during BW is the ankle joint. The knee and hip joint did not
      generate propulsion power. 

PMID- 23541767
TI  - The decapping scavenger enzyme DCS-1 controls microRNA levels in Caenorhabditis
      elegans.
AB  - In metazoans, microRNAs play a critical role in the posttranscriptional
      regulation of genes required for cell proliferation and differentiation.
      MicroRNAs themselves are regulated by a multitude of mechanisms influencing their
      transcription and posttranscriptional maturation. However, there is only sparse
      knowledge on pathways regulating the mature, functional form of microRNA. Here,
      we uncover the implication of the decapping scavenger protein DCS-1 in the
      control of microRNA turnover. In Caenorhabditis elegans, mutations in dcs-1
      increase the levels of functional microRNAs. We demonstrate that DCS-1 interacts
      with the exonuclease XRN-1 to promote microRNA degradation in an independent
      manner from its known decapping scavenger activity, establishing two molecular
      functions for DCS-1. Our findings thus indicate that DCS-1 is part of a
      degradation complex that performs microRNA turnover in animals.

PMID- 23541769
TI  - A double-barrel superficial temporal artery-to-superior cerebellar artery (STA
      SCA) and STA-to-posterior cerebral artery (STA-PCA) bypass for revascularization
      of the basilar apex.
AB  - Basilar apex aneurysms are challenging lesions for both microsurgical and
      endovascular therapy. In patients in whom direct clipping and coil embolization
      are not options, cerebral revascularization and occlusion of the basilar artery
      is a possible treatment strategy. We report a patient with a large basilar apex
      aneurysm treated by double-barrel anastomoses of the superficial temporal artery
      to the superior cerebellar artery (STA-SCA) and the STA to the posterior cerebral
      artery (STA-PCA) followed by occlusion of the basilar artery below the SCAs. A
      double-barrel bypass augments blood flow to the brainstem. We report a novel
      bypass option for augmenting blood flow to the basilar apex and brainstem.

PMID- 23541768
TI  - Two antagonistic clock-regulated histidine kinases time the activation of
      circadian gene expression.
AB  - The cyanobacterial circadian pacemaker consists of a three-protein clock--KaiA,
      KaiB, and KaiC--that generates oscillations in the phosphorylation state of KaiC.
      Here we investigate how temporal information encoded in KaiC phosphorylation is
      transduced to RpaA, a transcription factor required for circadian gene
      expression. We show that phosphorylation of RpaA is regulated by two antagonistic
      histidine kinases, SasA and CikA, which are sequentially activated at distinct
      times by the Kai clock complex. SasA acts as a kinase toward RpaA, whereas CikA,
      previously implicated in clock input, acts as a phosphatase that dephosphorylates
      RpaA. CikA and SasA cooperate to generate an oscillation of RpaA activity that is
      distinct from that generated by either enzyme alone and offset from the rhythm of
      KaiC phosphorylation. Our observations reveal how circadian clocks can precisely
      control the timing of output pathways via the concerted action of two oppositely
      acting enzymes.

PMID- 23541770
TI  - Molecular cloning and expression analysis of chymotrypsin-like serine protease
      from the redclaw crayfish (Cherax quadricarinatus): a possible role in the junior
      and adult innate immune systems.
AB  - A novel chymotrypsin-like serine protease (CLSP) was isolated from the
      hepatopancreas of the redclaw crayfish Cherax quadricarinatus (Cq-chy). The full
      length cDNA of Cq-chy contains 951 nucleotides encodes a peptide of 270 amino
      acids. The mature peptide comprising 223 amino acids contains the conserved
      catalytic triad (H, D, and S). Similarity analysis showed that Cq-chy shares high
      identity with chymotrypsins from the fiddler crab; Uca pugilator. Cq-chy mRNA
      expression in C. quadricarinatus was shown to be: (a) tissue-related with the
      highest expression in the hepatotpancreas and widely distributed, (b) highly
      responsive in the hepatopancreas to White Spot Syndrome Virus (WSSV) challenge,
      and (c) differently regulated in immature and adult crayfish. In this study we
      successfully isolated Cq-chy. Our observations indicate that Cq-chy is
      differently involved in the immature and adult innate immune reactions, thus
      suggesting a role for CLSPs in the invertebrate innate immune system.

PMID- 23541771
TI  - NADP+ -dependent IDH1 R132 mutation and its relevance for glioma patient
      survival.
AB  - The isocitrate dehydrogenase 1 (IDH1) mutation occurs in high frequency in glioma
      and secondary glioblastoma (GBM). Mutated IDH1 produces the oncometabolite 2
      hydroxyglutarate rather than alpha-ketoglutarate or isocitrate. The
      oncometabolite is considered to be the major cause of the association between the
      IDH1 mutation and gliomagenesis. On the other hand, the IDH1 mutation in GBM is
      associated with prolonged patient survival. This association is not well
      understood yet but IDH1 involvement in epigenetic silencing of O-6-methylguanine
      DNA methyltransferase (MGMT), a DNA repair enzyme is considered to be an
      important mechanism. However, it was shown recently that the IDH1 mutation and
      MGMT silencing are independent prognostic factors. Here, we hypothesize that the
      IDH1 mutation reduces the capacity to produce NADPH and thus reduces the capacity
      to scavenge reactive oxygen species that are generated during irradiation and
      chemotherapy. IDH1 activity is responsible for two-thirds of the NADPH production
      capacity in normal brain, whereas the IDH1 mutation reduces this capacity by
      almost 40%. Therefore, we hypothesize that the reduced NADPH production capacity
      due to the IDH1 mutation renders GBM cells more vulnerable to irradiation and
      chemotherapy thus prolonging survival of the patients.

PMID- 23541772
TI  - Exploratory factor analysis with small sample sizes: a comparison of three
      approaches.
AB  - Exploratory factor analysis (EFA) has emerged in the field of animal behavior as
      a useful tool for determining and assessing latent behavioral constructs. Because
      the small sample size problem often occurs in this field, a traditional approach,
      unweighted least squares, has been considered the most feasible choice for EFA.
      Two new approaches were recently introduced in the statistical literature as
      viable alternatives to EFA when sample size is small: regularized exploratory
      factor analysis and generalized exploratory factor analysis. A simulation study
      is conducted to evaluate the relative performance of these three approaches in
      terms of factor recovery under various experimental conditions of sample size,
      degree of overdetermination, and level of communality. In this study,
      overdetermination and sample size are the meaningful conditions in
      differentiating the performance of the three approaches in factor recovery.
      Specifically, when there are a relatively large number of factors, regularized
      exploratory factor analysis tends to recover the correct factor structure better
      than the other two approaches. Conversely, when few factors are retained,
      unweighted least squares tends to recover the factor structure better. Finally,
      generalized exploratory factor analysis exhibits very poor performance in factor
      recovery compared to the other approaches. This tendency is particularly
      prominent as sample size increases. Thus, generalized exploratory factor analysis
      may not be a good alternative to EFA. Regularized exploratory factor analysis is
      recommended over unweighted least squares unless small expected number of factors
      is ensured. 

PMID- 23541773
TI  - Parents' perceptions of a patient portal for managing their child's chronic
      illness.
AB  - Through interviews, we sought to describe parents' perceptions of a patient
      portal for the management of their child's chronic illness. Parents perceive
      patient portals as beneficial, providing easier communication with care
      providers, convenience, a sense of control, reduced anxiety, and reassurance.
      Future research should aim to quantitate these benefits. 

PMID- 23541774
TI  - Arginine metabolism in patients with cystic fibrosis.

PMID- 23541775
TI  - Contemporary outcomes in vascular patients who require preoperative coronary
      stent.
AB  - BACKGROUND: The documented risks of preoperative coronary revascularization prior
      to vascular surgery have led to a marked reduction in the role of percutaneous
      coronary intervention (PCI) during preoperative risk stratification. However,
      many patients with peripheral arterial disease are first identified immediately
      after a PCI for an acute coronary syndrome. We sought to determine the risks
      associated with these patients who then go on to have a peripheral arterial
      intervention (open operation or endovascular procedure). We hypothesized that
      there was no difference in outcomes in patients whose medical condition required
      PCI with coronary stent placement prior to a vascular operation compared with a
      control cohort of nonstented patients who underwent a vascular operation alone.
      We report the vascular operative outcomes in a contemporary cohort of vascular
      patients who had PCI with coronary stent placement for an acute event. METHODS:
      We performed a retrospective cohort analysis, utilizing administrative data, of
      3,678 vascular patients from 2005 to 2010 at a tertiary care hospital. Two groups
      were defined: patients with preoperative PCI and coronary stent placement within
      1 year prior to vascular operation (N = 101, mean age 66 +/- 1.22 years, 51.5%
      men); and patients with no PCI prior to vascular operation (N = 3,577, mean age
      60 +/- 0.27 years, 46.37% men). Cardiovascular risk factors and complications
      derived from ICD-9 codes were used to parse data after open peripheral vascular
      surgery, endovascular repair, or amputation. Primary outcomes were death,
      nonfatal myocardial infarction, major adverse cardiac event (MACE, defined as
      death, myocardial infarction, or subsequent coronary revascularization) or
      bleeding. RESULTS: Univariate analysis showed significant differences in both
      demographic and outcome analysis in patients with and without prior coronary
      stent. Patients with a recent PCI followed by a vascular procedure were more
      likely to undergo an endovascular procedure (75.3% vs. 64.5%, odds ratio = 1.67,
      P = 0.028). These patients also had 11 of 20 cardiovascular risk factors,
      significantly higher than in those without a prior PCI. Multivariate subgroup
      analysis indicated that patients with a prior coronary stent were more likely to
      have an episode of congestive heart failure (CHF) after 1 year of surgery (16.8%,
      P = 0.045). In addition, an acute cardiac ischemic event was more likely within 1
      year (2.0%, P = 0.036) and beyond 1 year (4.0%, P = 0.022) of surgery.
      Importantly, there was no significant increase in death, myocardial infarction,
      MACE, or bleeding in patients with a preoperative coronary stent. CONCLUSIONS:
      Patients who underwent PCI with coronary stent and then went on to require a
      vascular procedure had significantly more cardiovascular (CV) risk factors and
      were more likely to have an endovascular procedure than those patients without
      preoperative PCI. When controlling for CV risk factors and procedure type, there
      was no significant difference in death, MI, MACE, or bleeding complications
      between the groups.

PMID- 23541776
TI  - Novel use of a gastrointestinal stapler for diaphragm division during
      thoracoabdominal aortic exposure.
AB  - A significant portion of the morbidity associated with a thoracoabdominal
      approach to the suprarenal aorta is due to postoperative pulmonary dysfunction. A
      contributing factor to this dysfunction is division of the diaphragm during
      surgical exposure and subsequent repair upon completion of the operation. In this
      brief technical report, we describe a novel technique using a gastrointestinal
      stapler to divide the diaphragm that is rapid, hemostatic, and aids with
      reapproximation at the completion of the case. This method of diaphragm division
      is quicker and less traumatic and has the potential to decrease the incidence of
      postoperative pulmonary dysfunction. 

PMID- 23541777
TI  - Resection of sarcoma involving the intrahepatic vena cava: report of 2 cases from
      a specialized center.
AB  - BACKGROUND: Primary leiomyosarcoma (LMS) of the hepatic vena cava is a rare
      malignancy that has only been published in case reports. Only a few cases with
      successful R0 resection have been reported in the literature. METHODS: We report
      2 similar cases of extended primary LMS of the intrahepatic inferior vena cava
      (IVC). Both patients previously underwent operations in nonspecialized centers
      that resulted in inadequate tumor resection. After admission to a high-volume
      center focusing on the treatment of patients with sarcoma, R0 resection was
      feasible with a multimodal therapeutic treatment approach. RESULTS: Radical
      complete tumor resection was achieved by means of extended right-sided
      hemihepatectomy (segments V-VIII and I), en bloc resection, and prosthetic
      replacement of the IVC and nephrectomy in 1 patient. Both patients are currently
      tumor-free and healthy 6 months postoperatively. CONCLUSIONS: Patients with such
      complex tumors should be referred to centers with specialized surgeons who can
      preoperatively estimate whether complete resection may be possible and who are
      capable of performing such delicate interventions.

PMID- 23541778
TI  - Delayed presentation of a thoracic aortic injury with a vertebral pedicle screw.
AB  - Iatrogenic aortic injuries by pedicle screws are rare but serious complications
      of spinal fixation surgery. We report the case of a 55-year-old man who underwent
      surgical correction of traumatic thoracic vertebral fractures at another
      institution. At 6-month follow-up, computed tomography revealed a nonhealing of
      the fractures, and a T4 misplaced pedicle screw penetrating the descending
      thoracic aorta. The patient underwent open aortic repair associated with the
      anterior vertebral column reconstruction and posterior arthrodesis revision by a
      vascular and orthopedic surgery team simultaneously.

PMID- 23541779
TI  - Endovascular treatment of aortic and primitive iliac artery aneurysms associated
      with Behcet disease.
AB  - Behcet disease is a systemic vasculitis that can cause vascular complications. We
      describe a 42-year-old woman with an aortic aneurysm and common right iliac
      aneurysm, both saccular and complicating Behcet disease. The patient was
      successfully treated by an endovascular method, which currently seems to be the
      best therapeutic choice given the frequent anastomotic complications of
      conventional surgical treatment.

PMID- 23541780
TI  - A shift toward endovascular repair for vascular complications in lumbar disc
      surgery during the last decade.
AB  - BACKGROUND: The purpose of this study is to evaluate 2 patients who underwent
      endovascular repair directly after acute life-threatening vascular injury
      complicating lumbar disc surgery, and to update an overview of the literature
      from 2002 to gain insights into characteristics, diagnosis, treatment, and
      outcomes of this rare, life-threatening complication. METHODS: PubMed was
      searched for English language studies on vascular injury (lacerations,
      arteriovenous fistulas, and pseudoaneurysms) complicating lumbar disc surgery by
      a posterior approach published from 2002. Two cases from the authors' institute
      were added to the review. Information on patient characteristics, diagnosis,
      treatment strategies, and outcomes were extracted by 2 independent reviewers.
      CASE REPORTS: The first case describes a 54-year-old man who underwent lumbar
      disc surgery through a posterior approach (L5-S1) and became hypotensive
      intraoperatively. Angiography revealed an injury of the right internal iliac
      artery. Bleeding was successfully repaired by endovascular repair (acute balloon
      occlusion followed by coiling). The second case describes a 51-year-old women who
      suddenly became hypotensive during L4 through L5 discectomy caused by bleeding
      from a laceration in the right common iliac artery. Angiography confirmed the
      diagnosis, and the bleeding was successfully treated through endovascular repair
      with a covered stent. RESULTS: A total of 56 cases from 34 articles were found in
      the literature since 2002, including lacerations, arteriovenous fistulas, and
      pseudoaneurysms. Two cases from the authors' institute were added to the review.
      Vascular injury was recognized intraoperatively in 36%, and within 24 hours
      postsurgery in 28%. The common iliac artery was most frequently affected (51%),
      followed by the iliac vein (23%). All lacerations were detected during surgery,
      whereas most arteriovenous fistulas and pseudoaneurysms were detected in the long
      term. Treatment consisted of open surgical repair (57%) or endovascular repair
      (43%). All patients survived surgery. CONCLUSIONS: Publication bias might play a
      role in the literature of this area because all cases survived surgery, whereas
      mortality rates for this condition are high. However, early recognition,
      diagnosis, and prompt surgical repair are essential to prevent fatal outcomes in
      vascular injuries complicating lumbar disc surgery. Endovascular repair is a
      minimally invasive, fast, and efficient treatment modality that is increasingly
      and preferably used because of its low morbidity and mortality.

PMID- 23541781
TI  - Flanged elephant trunk technique at distal anastomosis for total arch replacement
      with multibranched arch graft.
AB  - Bleeding from the distal anastomosis suture line in total arch replacement is a
      serious and major concern for surgeons. We present a simple, flanged elephant
      trunk technique to reduce or eliminate bleeding from the distal anastomosis
      suture line in total arch replacement using a multibranched arch graft. This
      method allows not only a secure and reinforced distal anastomosis, but also
      simultaneous elephant trunk insertion. 

PMID- 23541782
TI  - New insights into the effects of primary hyperparathyroidism on the cortical and
      trabecular compartments of bone.
AB  - In primary hyperparathyroidism (PHPT), protracted elevation of serum parathyroid
      hormone (PTH) is held to be associated with cortical, but not trabecular, bone
      loss. However, an alternative explanation for the apparent preservation of
      trabecular bone is fragmentation of the cortex by intracortical remodeling. The
      cortical fragments resemble trabeculae and so may be erroneously included in the
      quantification of 'trabecular' bone density. To test this hypothesis, we compared
      bone microarchitecture in 43 patients with untreated PHPT (mean 62.9 years, range
      31-84) with 47 healthy age-matched controls and 25 patients with surgically
      treated PHPT (63.6 years, 30-82). Images of the distal radius and tibia were
      acquired using high-resolution peripheral quantitative CT and analysed using
      StrAx1.0, a new software program that quantifies bone morphology in-vivo. Results
      were expressed as the mean number of standardized deviations (SD) from the age
      specific mean (Z scores, mean+/-SEM). In subjects with PHPT, total tibial
      cortical area was reduced -0.26+/-0.08 SD; p=0.002). Cortical volumetric bone
      mineral density (vBMD) was reduced (-0.29+/-0.06 SD; p<0.001) due to higher
      cortical porosity (0.32+/-0.06 SD; p<0.001) and lower tissue mineralization
      density (-0.21+/-0.06 SD; p=0.002). Medullary area was increased (0.26+/-0.08 SD;
      p=0.002) and trabecular vBMD was reduced (-0.14+/-0.04 SD; p<0.001). In subjects
      who underwent successful parathyroidectomy, cortical area (-0.18+/-0.10 SD; NS)
      and medullary area (0.18+/-0.10 SD; NS) did not differ from controls. Cortical
      vBMD was reduced (-0.15+/-0.05 SD; p=0.003) due to high porosity (0.15+/-0.05 SD;
      p=0.006), values numerically lower than in untreated PHPT. Tissue mineralization
      density (-0.26+/-0.04 SD; p<0.001) and trabecular vBMD were reduced (-0.16+/-0.04
      SD, p<0.001). The results were similar in the distal radius. In PHPT, chronically
      elevated endogenous PTH does not spare trabecular bone; it causes bone loss and
      microarchitectural deterioration in both cortical and trabecular compartments of
      bone.

PMID- 23541783
TI  - Evaluation of an indirect rapid immunohistochemistry test for the differentiation
      of rabies virus variants.
AB  - Cost effective diagnostic tests are needed in rabies virus (RABV) enzootic areas
      to study the prevalence, distribution, and transmission of rabies virus among
      reservoir hosts. To reduce the associated costs of acquiring and maintaining
      specialized laboratory equipment, an indirect rapid immunohistochemistry test
      (IRIT), for the detection and differentiation of RABV variants, was evaluated by
      traditional light microscopy. The IRIT utilizes fresh frozen brain touch
      impressions or cell culture monolayers fixed in buffered formalin, a panel of
      murine anti-nucleoprotein monoclonal antibodies (mAb-N) and commercially
      available biotin-labeled goat anti-mouse antibody. In this study, 96 RABV
      isolates, representing 20 RABV variants previously determined by antigenic typing
      using a panel of mAb-N and the indirect fluorescent antibody test (IFA), and
      genetic sequence analysis were characterized by IRIT and the results compared.
      The IRIT results revealed distinct reactivity patterns associated with current
      and historical RABV reservoir hosts similar to IFA test and genetic sequence
      analysis. Evaluation of suspected RABV samples through IRIT does not require
      specialized equipment and is possible to perform in a field setting.
      Additionally, commercially available labeled secondary antibodies permit the use
      of a standard panel of unlabeled primary mAbs, without the need for fluorescence
      microscopy, and should augment existing attempts at antigenic characterization
      during canine rabies elimination campaigns in developed and developing countries.
      These results are useful in studying the epizootiology of rabies and inferring
      the source of infection when unknown.

PMID- 23541784
TI  - Direct RT-PCR from serum enables fast and cost-effective phylogenetic analysis of
      bovine viral diarrhoea virus.
AB  - Studies of the molecular epidemiology of viral diseases are dependent on the
      analysis of large numbers of samples from infected individuals, and the assembly
      of relevant sequence databases are a prerequisite to investigate chains of
      infection. As part of research in support of the Scottish BVDV eradication
      campaign, we have established a direct RT-PCR method for the high throughput
      amplification and analysis of the informative 5'-untranslated region of the BVDV
      genome. Heat-treatment followed by a one-step RT-PCR, performed in 96-well
      plates, produced sufficient material for sequence analysis from 0.5 MUl of serum
      or plasma. Of 93 samples assayed, only five failed to give full sequence data for
      the region amplified and these were subsequently successfully analysed in single
      tube format reactions. This approach improved the speed of analysis, reduced
      costs, operator time and the potential for contamination, and may allow analysis
      of samples for which volumes are too low for conventional RNA isolation. It also
      has the potential for wider application in both human and animal disease research
      in which high throughput and low cost would increase the size of datasets that
      can be obtained.

PMID- 23541785
TI  - Effectiveness of three types of rapid tests for the detection of hepatitis C
      virus antibodies among blood donors in Alexandria, Egypt.
AB  - Hepatitis C is one of the most important diseases transmitted through screened
      improperly blood donation. The detection of HCV antibodies is performed by enzyme
      immunoassays (EIA) or supplementary assays (immunoblots). However, these methods
      are not well-suited to developing countries due to their high cost and
      technicality. The effectiveness of three different rapid tests for the detection
      of anti-HCV antibodies was evaluated compared to third-generation ELISA among
      blood donors attending the blood bank of Medical Research Institute in
      Alexandria, Egypt. The results were compared subsequently to the results of HCV
      RNA obtained by qualitative reverse transcriptase polymerase chain reaction (RT
      PCR). The three types of rapid tests showed a specificity of 100% and
      sensitivities of 96-98% compared to ELISA. Compared to RT-PCR, ELISA and all
      three types of rapid tests showed an almost equal specificity (77-78.5%). ELISA
      showed 100% sensitivity while all three types of rapid tests showed equal
      sensitivities of 97% compared to RT-PCR. The rapid tests showed good performance
      for detecting anti-HCV antibodies in the sera of blood donors compared to ELISA.
      Therefore, the present study recommends the use of the tested rapid tests to
      screen for anti-HCV among blood donors in resource-limited countries as an
      alternative for conventional ELISA.

PMID- 23541786
TI  - Store-operated calcium entry could prevent continuous spiking of membrane
      potential to sustain normal intracellular calcium oscillations and normal
      potential bursting in pancreatic beta-cells.
AB  - We propose a dynamical store-operated calcium entry (SOCE) model to analyze the
      complex role of SOCE in modulating calcium oscillations and electrical activity
      in pancreatic beta-cells and provide a new mathematical insight. Using this
      model, we simulate the SOCE role in a number of cases with different SOCE
      conductances. When the SOCE conductance is set to 0 or very small (5 pS), our
      numerical simulation conforms to the experimental observation that endoplasmic
      reticulum (ER) calcium can sustain normal calcium oscillations and the depletion
      of ER calcium transforms the normal calcium oscillations into a sustained calcium
      increase with oscillations of much higher frequency and much smaller amplitude,
      and transforms the normal membrane potential oscillations to a pattern of
      continuous spiking. When the SOCE conductance is increased to 20 pS and the ER
      calcium is depleted, our numerical simulation conforms to the other experimental
      observation that the normal calcium and potential oscillations are sustained and
      augmented a little bit. Moreover, the oscillation frequency is increased a very
      little bit. A further increase of the conductance to 35 pS slows down the
      oscillation a little bit. This numerical evidence suggests that a sufficiently
      large SOCE can prevent the continuous spiking of membrane potential to sustain
      the normal calcium oscillations and the normal membrane potential bursting. A
      careful examination of our simulated dynamics of the ATP/ADP ratio, the ATP
      sensitive outward K(+) current, and the voltage-gated inward Ca(2+) current
      reveals that intracellular periodic Ca(2+) peaks perhaps resulted from SOCE might
      play a role in stabilizing the membrane potential at its resting level (avoiding
      the continuous spiking) for a certain period of time by accelerating ATP
      consumption, reducing the ratio ATP/ADP, opening the ATP-sensitive potassium
      channel, and repolarizing the membrane potential.

PMID- 23541787
TI  - Components of the model of the clinical practice of emergency medicine: a survey
      of American Board of Emergency Medicine diplomates.
AB  - BACKGROUND: The Model of the Clinical Practice of Emergency Medicine is the basis
      for the content specifications of all American Board of Emergency Medicine (ABEM)
      examinations. This study describes the frequency with which ABEM diplomates
      diagnose and manage the conditions and components listed in the Model of the
      Clinical Practice of Emergency Medicine. OBJECTIVES: The objectives of this study
      were to determine the frequency with which ABEM diplomates diagnose and manage
      the conditions and components described in the Model of the Clinical Practice of
      Emergency Medicine. METHODS: The listing of conditions and components of the
      Model of the Clinical Practice of Emergency Medicine were sent to 16,230 randomly
      selected ABEM diplomates. One of five surveys was sent to each diplomate. Each
      condition and component was assessed by participants for the frequency that
      emergency physicians diagnose (D) and manage (M) that condition, as seen in their
      practice of Emergency Medicine. RESULTS: Of the 16,230 surveys sent, 5006 were
      returned (30.8% response rate). The genders of the respondents were 75% male and
      24% female. The ages of the respondents were primarily in the age 40-49 years,
      and 30-39 years age groups. All categories of the listing of conditions and
      components of the Model of the Clinical Practice of Emergency Medicine were
      encountered frequently in the practice of Emergency Medicine, as indicated by
      study participants. CONCLUSIONS: A survey of practicing ABEM diplomates was
      useful in defining the frequency with which specific conditions and components
      are diagnosed and managed in the practice of Emergency Medicine.

PMID- 23541788
TI  - [Normal pressure hydrocephalus: prognostic value of height in patients treated
      with an identical shunt system].
AB  - INTRODUCTION: Normal pressure hydrocephalus (NPH) is a clinical entity frequently
      managed by means of a cerebrospinal fluid shunt. Hydrodynamic hypotheses consider
      hydrostatic pressure (as well as height) a very important variable for shunt
      system function. However, we did not find empirical studies supporting the
      influence of height on clinical response in the literature. Our objective was to
      study the prognostic value of height, as a variable related to hydrostatic
      pressure, when an identical shunt system is used. MATERIAL AND METHOD: A
      prospective series of 61 idiopathic NPH cases was analyzed. All cases were
      shunted by means of a ventricle-peritoneal system with a 100mmH2O opening
      pressure valve. Anthropometric, clinical, radiological and pressure variables
      were registered, as well as delay for treatment, improvement and complications.
      RESULTS: 78.7% of cases improved after shunting. This group of patients was
      significantly taller (P=.005) than the group without response (median value 165cm
      versus 152cm). There was also a significant correlation between height and
      ventricular size decrease after the shunt. CONCLUSIONS: In our series opening
      valve pressure was a constant (100mmHg) and we could consequently focus on the
      effect of hydrostatic pressure (height). Moreover, we found a positive predictive
      value for taller patients, probably because we had selected an opening pressure
      especially suitable for them. Current gravitational valve shunt systems also
      recommend considering patient height when customising the system. Our study
      empirically supports this idea.

PMID- 23541789
TI  - Activity measurement of gamma-ray emitters in aerosol filters exposed in
      Lithuania, in March-April 2011.
AB  - Two aerosol sampling stations in Lithuania were simultaneously used for assessing
      consequences of the accident at the Fukushima Dai-ichi nuclear power plant. The
      maximum activity concentrations of (129 m)Te, (131)I, (134)Cs and (137)Cs were
      0.59 +/- 0.06, 3.5 +/- 0.3, 0.90 +/- 0.08, 0.90 +/- 0.07 mBq m(-3) at station #1
      in Vilnius, and 0.29 +/- 0.03, 1.0 +/- 0.1, 0.41 +/- 0.04, 0.41 +/- 0.0 4 mBq m(
      3) at station #2 in northeastern part of Lithuania, respectively.

PMID- 23541790
TI  - Radioactive contamination monitoring for the Korean public following Fukushima
      nuclear accident.
AB  - On March 11, 2011, as a result of the Great East Japan Earthquake, severe damage
      to the Fukushima nuclear power plant caused the release of radioactive materials.
      We conducted radioactive contamination monitoring for Korean residents in Japan
      and Korean travelers to East Japan after the accident. More than 800 members of
      the Korean public were surveyed for personal monitoring. Measured levels of
      external and internal contamination were within the screening levels for each
      monitoring method. 

PMID- 23541791
TI  - Antimalarial chemoprophylaxis and the risk of neuropsychiatric disorders.
AB  - BACKGROUND: Case reports and epidemiological studies have associated the use of
      mefloquine with neuropsychiatric adverse events. METHODS: We used the General
      Practice Research Database to conduct a follow-up study with a nested case
      control analysis. We assessed the risk of developing first-time anxiety, stress
      related disorders/psychosis, depression, epilepsy or peripheral neuropathies in
      patients using mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil
      for malaria chemoprophylaxis, as compared to unexposed travelers. RESULTS:
      Compared to non-users of antimalarials, the adjusted odds ratio in the nested
      case-control analysis for users of mefloquine, chloroquine and/or proguanil, or
      atovaquone/proguanil were 0.71 (95% CI 0.56-0.90), 1.04 (95% CI 0.74-1.46), and
      0.73 (95% CI 0.61-0.86) for anxiety or stress-related disorders combined, 0.54
      (95% CI 0.41-0.71), 1.06 (95% CI 0.71-1.59), and 0.75 (95% CI 0.62-0.91) for
      depression, 0.69 (95% CI 0.35-1.36), 1.41 (95% CI 0.54-3.67), and 0.75 (95% CI
      0.42-1.36) for epilepsy, and 1.22 (95% CI 0.50-2.99), 1.59 (95% CI 0.41-6.15),
      and 1.05 (95% CI 0.54-2.03) for neuropathies, respectively. The risk of all
      outcomes was higher in females than in males across all exposure categories.
      CONCLUSIONS: The risk of neuropsychiatric disorders was similar for users and for
      non-users of anti-malarial chemoprophylaxis, with evidence for elevated risks in
      some subgroups.

PMID- 23541793
TI  - Eukaryotic Argonautes come into focus.
AB  - Despite the fact that different classes of small RNAs are generated by largely
      different biogenesis pathways, all mature small RNAs associate with an Argonaute
      family member to form the RNA-induced silencing complex (RISC). Gene silencing by
      RISC could not be studied in molecular detail because structural information on
      eukaryotic Argonautes was lacking. Recently, however, the structure of human
      Argonaute-2 (hAgo2), a model for RISC function, was determined in complexes with
      heterogeneous guide RNA and in complexes with a specific miRNA. We review the
      exciting advances that these two structures, together with the structure of a
      budding yeast Argonaute, brought to the field of eukaryotic RNA interference
      (RNAi), and how they will enable a more detailed mechanistic understanding of
      eukaryotic RISC.

PMID- 23541794
TI  - Preserved foods associated with increased risk of ovarian cancer.
AB  - OBJECTIVE: To investigate the association between consumption of preserved foods
      and risk of epithelial ovarian cancer in southern Chinese women. METHODS: A
      hospital-based case-control study was undertaken in Guangzhou, Guangdong
      Province, from 2006 to 2008. Participants were 500 incident epithelial ovarian
      cancer patients and 500 controls, with a mean age 59 years. Information on
      habitual food consumption was obtained by face-to-face interview using a
      validated and reliable food frequency questionnaire. Logistic regression analyses
      were performed to assess the association between preserved foods intake and the
      ovarian cancer risk. RESULTS: The ovarian cancer patients consumed more preserved
      foods (median 15.5, interquartile range (IQR) 18.2g/day) than controls (median
      13.8, IQR 20.5 g/day), p<0.001. The adjusted odds ratios of ovarian cancer was
      1.78 (95% confidence interval 1.35 to 2.34) for women consuming more than 13.5 g
      of preserved vegetables and preserved meats per day relative to those below.
      Similar two-fold increases in risk at high level of intake were also evident for
      serous and mucinous subtypes of epithelial ovarian tumours. CONCLUSION: Intake of
      preserved foods was positively associated with the incidence of epithelial
      ovarian cancer in southern Chinese women.

PMID- 23541792
TI  - On the role of 25-hydroxycholesterol synthesis by glioblastoma cell lines.
      Implications for chemotactic monocyte recruitment.
AB  - Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor
      and is invariably fatal to affected patients. Oxysterols belong to a class of
      bioactive lipids that are implicated in neurological disease and are associated
      with various types of cancer. Here, we investigated expression and
      transcriptional regulation of cholesterol 25-hydroxylase (CH25H) in human U87MG
      and GM133 glioblastoma cell lines. We demonstrate that in both cell lines
      transcription and translation of CH25H are increased in response to TNFalpha and
      IL1beta. In parallel, both cell lines upregulate 25-hydroxycholesterol (25-OHC)
      synthesis and secretion to levels comparable to bone marrow-derived mouse
      macrophages under inflammatory conditions. To determine whether 25-OHC acts as
      chemoattractant for tumor-associated macrophages, the human THP-1 monoblastic
      leukemia cell line was treated with varying amounts of the oxysterol. Experiments
      revealed that 25-OHC and lipid extracts isolated from GM133-conditioned medium
      (containing 7-fold higher 25-OHC concentrations than U87MG medium) induce
      chemotactic migration of THP-1 cells. Of note, 25-OHC also induced the migration
      of primary human peripheral blood monocytes. In response to exogenously added 25
      OHC, THP-1 cells reorganized intermediate filament-associated vimentin to more
      cortical and polarized structures. Chemotactic migration of monocytes in response
      to 25-OHC was pertussis toxin-sensitive, indicating the involvement of G protein
      coupled receptors. Using RNA interference we demonstrated that G protein-coupled
      receptor 183 (EBI2) contributes to 25-OHC-mediated chemotactic migration of THP-1
      cells. These in vitro data indicate that GBM-derived and secreted 25-OHC may be
      involved in the recruitment of immune-competent cells to a tumor via EBI2. 

PMID- 23541796
TI  - The puzzle of close surgical margins is not puzzling.

PMID- 23541795
TI  - Risk of residual disease and invasive carcinoma in women treated for
      adenocarcinoma in situ of the cervix.
AB  - OBJECTIVE: Cervical adenocarcinoma in situ (AIS) is increasing in incidence among
      reproductive-age women. Cervical conization is an alternative to hysterectomy
      that allows future fertility, however reports regarding the risk of residual AIS
      and underlying adenocarcinoma are conflicting. The purpose of this study was to
      determine the outcomes of a large cohort of women treated for AIS. METHODS: The
      medical records of 180 women with cervical AIS evaluated at the University of
      Texas MD Anderson Cancer Center and its outlying clinics between 1983 and 2011
      were reviewed for demographic information, treatment history, pathologic findings
      and outcomes. RESULTS: The mean age at diagnosis was 33.8years (range 17.6
      76.1years). 172 of the 180 women had at least one cone biopsy performed, with 110
      (64.0%) undergoing a cold knife cone (CKC), and 62 (36.0%) undergoing a loop
      electrosurgical excision procedure (LEEP) as their initial method of treatment.
      Positive margins were noted in 35.0% of patients undergoing CKC compared with
      55.6% undergoing LEEP (p=0.017). 71 patients ultimately underwent hysterectomy
      with residual disease noted in 10 patients (14.1%), 8 patients (11.3%) with
      residual AIS and 2 patients (2.8%) with invasive carcinoma. Of the 101 patients
      who did not undergo hysterectomy, 2 patients (2.0%) developed recurrent AIS at a
      median of 27.5months (range 18-37months) from the last cone, and none developed
      invasive carcinoma. CONCLUSION: Patients undergoing conservative management for
      AIS with cervical conization alone should be monitored closely and counseled
      regarding the potential risks of residual and recurrent disease, even when
      negative cone margins are obtained.

PMID- 23541797
TI  - High prevalence of femoral head necrosis in Mucopolysaccharidosis type III
      (Sanfilippo disease): a national, observational, cross-sectional study.
AB  - BACKGROUND: Sanfilippo disease, or Mucopolysaccharidosis type III (MPS III), is a
      lysosomal storage disorder and a member of the mucopolysaccharidoses (MPSs). MPS
      III is clinically characterized by progressive neurodegeneration. Skeletal
      disease is not felt to be an important clinical component in MPS III patients,
      unlike in the other MPSs. We conducted radiographic studies in a relatively large
      group of MPS III patients and detected a high prevalence of osteonecrosis of the
      femoral head (ONFH). METHODS: Thirty-three patients were included in the study.
      All the patients underwent an X-ray of the pelvis (anteroposterior view). All the
      X-rays were evaluated by a single, blinded radiologist using a modified Ficat
      classification system for ONFH (the stages ranged from 0 to IV, with increasing
      stages signifying more severe abnormalities). Clinical symptoms possibly related
      to hip disease were recorded. The patients were divided into different phenotypes
      based on mutational analysis and their plasma heparan sulfate (HS) levels.
      RESULTS: In 21 of the 33 patients, the disease severity could be predicted by
      genotype. In 11 of the 12 remaining patients, the phenotype could be assessed via
      the plasma HS levels. Eight patients (24%) exhibited signs of ONFH (Ficat
      stage>=I), and 6 (75%) of them had bilateral changes. None of the patients with
      attenuated MPS III (n=14) had ONFH. In 6 of the patients with a severe phenotype,
      hip dysplasia was detected as an additional finding. The 7 patients with Ficat
      stages >= II reported hip pain. CONCLUSIONS: Femoral head disease, which
      resembles ONFH, is common in patients with the severe MPS III phenotype. An
      evaluation of hip disease should be included in follow-up visits with MPS III
      patients.

PMID- 23541798
TI  - Fiber density estimation from single q-shell diffusion imaging by tensor
      divergence.
AB  - Diffusion-weighted magnetic resonance imaging provides information about the
      nerve fiber bundle geometry of the human brain. While the inference of the
      underlying fiber bundle orientation only requires single q-shell measurements,
      the absolute determination of their volume fractions is much more challenging
      with respect to measurement techniques and analysis. Unfortunately, the usually
      employed multi-compartment models cannot be applied to single q-shell
      measurements, because the compartment's diffusivities cannot be resolved. This
      work proposes an equation for fiber orientation densities that can infer the
      absolute fraction up to a global factor. This equation, which is inspired by the
      classical mass preservation law in fluid dynamics, expresses the fiber
      conservation associated with the assumption that fibers do not terminate in white
      matter. Simulations on synthetic phantoms show that the approach is able to
      derive the densities correctly for various configurations. Experiments with a
      pseudo ground truth phantom show that even for complex, brain-like geometries the
      method is able to infer the densities correctly. In-vivo results with 81 healthy
      volunteers are plausible and consistent. A group analysis with respect to age and
      gender show significant differences, such that the proposed maps can be used as a
      quantitative measure for group and longitudinal analysis.

PMID- 23541799
TI  - Voxel-based classification of FDG PET in dementia using inter-scanner
      normalization.
AB  - Statistical mapping of FDG PET brain images has become a common tool in
      differential diagnosis of patients with dementia. We present a voxel-based
      classification system of neurodegenerative dementias based on partial least
      squares (PLS). Such a classifier relies on image databases of normal controls and
      dementia cases as training data. Variations in PET image characteristics can be
      expected between databases, for example due to differences in instrumentation,
      patient preparation, and image reconstruction. This study evaluates (i) the
      impact of databases from different scanners on classification accuracy and (ii) a
      method to improve inter-scanner classification. Brain FDG PET databases from
      three scanners (A, B, C) at two clinical sites were evaluated. Diagnostic
      categories included normal controls (NC, nA=26, nB=20, nC=24 for each scanner
      respectively), Alzheimer's disease (AD, nA=44, nB=11, nC=16), and frontotemporal
      dementia (FTD, nA=13, nB=13, nC=5). Spatially normalized images were classified
      as NC, AD, or FTD using partial least squares. Supervised learning was employed
      to determine classifier parameters, whereby available data is sub-divided into
      training and test sets. Four different database setups were evaluated: (i) "in
      scanner": training and test data from the same scanner, (ii) "x-scanner":
      training and test data from different scanners, (iii) "train other": train on
      both x-scanners, and (iv) "train all": train on all scanners. In order to
      moderate the impact of inter-scanner variations on image evaluation, voxel-by
      voxel scaling was applied based on "ratio images". Good classification accuracy
      of on average 94% was achieved for the in-scanner setups. Accuracy deteriorated
      for setups with mismatched scanners (79-91%). Ratio-image normalization improved
      all results with mismatched scanners (85-92%). In conclusion, automatic
      classification of individual FDG PET in differential diagnosis of dementia is
      feasible. Accuracy can vary with respect to scanner or acquisition
      characteristics of the training image data. The adopted approach of ratio-image
      normalization has been demonstrated to effectively moderate these effects.

PMID- 23541801
TI  - Delineating extrastriate visual area MT(V5) using cortical myeloarchitecture.
AB  - Visual area MT is a model of choice in primate neurophysiological and human
      imaging research of visual perception, due to its considerable sensitivity to
      moving stimuli and the strong direction selectivity of its neurons. While the
      location of MT(V5) in the non-human primate is easily identifiable based on gross
      anatomy and appears consistent between animals, this is less the case in human
      subjects. Functional localisation of human MT+ with moving stimuli can identify a
      group of motion-sensitive regions, but defining MT proper has proved more
      challenging. In this review we consider approaches to studying the cyto- and
      myleoarchitecture of this cortical area that may, in the future, allow
      identification of human MT in vivo based on anatomy.

PMID- 23541800
TI  - Real-time fMRI neurofeedback: progress and challenges.
AB  - In February of 2012, the first international conference on real time functional
      magnetic resonance imaging (rtfMRI) neurofeedback was held at the Swiss Federal
      Institute of Technology Zurich (ETHZ), Switzerland. This review summarizes
      progress in the field, introduces current debates, elucidates open questions, and
      offers viewpoints derived from the conference. The review offers perspectives on
      study design, scientific and clinical applications, rtfMRI learning mechanisms
      and future outlook.

PMID- 23541802
TI  - Towards a multimodal brain-computer interface: combining fNIRS and fTCD
      measurements to enable higher classification accuracy.
AB  - Previous brain-computer interface (BCI) research has largely focused on single
      neuroimaging modalities such as near-infrared spectroscopy (NIRS) or transcranial
      Doppler ultrasonography (TCD). However, multimodal brain-computer interfaces,
      which combine signals from different brain modalities, have been suggested as a
      potential means of improving the accuracy of BCI systems. In this paper, we
      compare the classification accuracies attainable using NIRS signals alone, TCD
      signals alone, and a combination of NIRS and TCD signals. Nine able-bodied
      subjects (mean age=25.7) were recruited and simultaneous measurements were made
      with NIRS and TCD instruments while participants were prompted to perform a
      verbal fluency task or to remain at rest, within the context of a block-stimulus
      paradigm. Using Linear Discriminant Analysis, the verbal fluency task was
      classified at mean accuracies of 76.1+/-9.9%, 79.4+/-10.3%, and 86.5+/-6.0% using
      NIRS, TCD, and NIRS-TCD systems respectively. In five of nine participants,
      classification accuracies with the NIRS-TCD system were significantly higher
      (p<0.05) than with NIRS or TCD systems alone. Our results suggest that multimodal
      neuroimaging may be a promising method of improving the accuracy of future brain
      computer interfaces.

PMID- 23541803
TI  - Rapid improvement of depression and psychotic symptoms in Huntington's disease: a
      retrospective chart review of seven patients treated with electroconvulsive
      therapy.
AB  - Many patients with Huntington's disease (HD) develop psychiatric symptoms such as
      depression and psychosis. For severe symptoms, electroconvulsive therapy (ECT)
      can be a valuable treatment. In this case series, we identified seven patients
      with HD who received ECT at Massachusetts General Hospital in the past 20 years.
      In all cases, ECT was well tolerated and produced improvement in psychiatric and
      behavioral symptoms. Our case series supports the hypothesis of a positive risk
      benefit ratio for ECT in patients with HD and severe depression or psychosis. 

PMID- 23541805
TI  - Recurrent trichobezoar due to trichophagia: a case report.
AB  - OBJECTIVE: Trichobezoar, a hair ball in the gastrointestinal tract, is usually
      the result of the urge to pull out one's own hair (trichotillomania) and swallow
      it (trichophagia). It is almost exclusively seen in young females and may cause
      serious medical complications. This case report will describe an adult female
      patient with recurrent trichobezoars. METHOD: Data for this case report was
      collected from peer-reviewed literature and treatment encounters by the
      consultation-liaison psychiatry unit; subsequent to obtaining informed consent.
      RESULTS: The personality characteristics, familial structure and domestic stress
      found in this case mirror the literature. We initiated behavioral interventions
      including habit reversal training and patient education in combination with
      pharmacologic therapy with clomipramine. CONCLUSION: Left untreated, trichophagia
      can cause a life-threatening emergency, requiring surgery. Recurrence of
      tichobezoars can be anticipated when the underlying emotional disorder is not
      addressed using multimodal management including psychiatric evaluation and
      treatment combined with surgical procedures.

PMID- 23541804
TI  - The association of psychosocial factors and obstetric history with depression in
      pregnant women: focus on the role of emotional support.
AB  - OBJECTIVE: Depression during pregnancy can negatively affect both maternal and
      fetal health. The benefits of early detection and treatment for antenatal
      depression have been emphasized. Therefore, we investigated risk factors for
      antenatal depression with a focus on emotional support. METHODS: We conducted a
      cross-sectional study of pregnant women (n=1262) enrolled from the local division
      of a community mental health center. All subjects completed self-report
      questionnaires that assessed depressive mood, emotional support and other risk
      factors. Associations between antenatal depression and potential risk factors
      including emotional support were analyzed by logistic regression analysis.
      RESULTS: Antenatal depression was associated with various biopsychosocial
      correlates: unmarried state, low education, cigarette smoking, low income,
      familial history of depression, past history of depression, physical abuse
      history, sexual abuse history, premenstrual syndrome, primiparity and unplanned
      pregnancy. When the associations of emotional support with antenatal depression
      were specified by its resources, current emotional support from partner [odds
      ratio (OR)=2.26, 95% confidence interval (CI)=1.94-2.64] and mother (OR=1.43, 95%
      CI=1.26-1.62) and past experience for emotional support from mother (OR=1.52, 95%
      CI=1.32-1.74), but not from father significantly influenced depression during
      pregnancy. CONCLUSIONS: The multidimensional biopsychosocial approach would be
      needed to identify and assess antenatal depression. Promoting emotional support
      from the partner, family member and, possibly, the health provider could be a
      protective effect against the development of antenatal depression.

PMID- 23541806
TI  - Myocardin-related transcription factor-A is a key regulator in retinoic acid
      induced neural-like differentiation of adult bone marrow-derived mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can
      differentiate into neuron cells under appropriate environment in vitro and in
      vivo. Retinoic acid (RA), a vitamin A derivative, is known to facilitate the
      neuronal differentiation of MSCs. However, the mechanism by which RA induced MSC
      differentiation into neuron-like cells is not completely understood. Here, we
      show that RA can induce neural-like differentiation of bone marrow-derived MSCs,
      as evidenced by the increase of neuron-specific marker expression and the
      gradually decreased resting membrane potential. Of note, myocardin-related
      transcription factor-A (MRTF-A), a major co-activator of serum response factor
      (SRF), was significantly activated and its nuclear localization was observed
      during RA-induced neural-like differentiation. MRTF-A is recently reported to
      function in the development of the nervous system. Our results demonstrated that
      dominant-negative form of MRTF-A (DN-MRTF-A) or shRNA-MRTF-A strongly inhibited
      upregulation of neural markers in response to RA. Furthermore, reporter assays
      with NF-H promoter indicated that RA and MRTF-A can synergistically activate NF-H
      transcription and enhance the mRNA expression of NF-H. These findings reveal that
      MRTF-A is a key regulator in all-trans RA-induced neural-like differentiation of
      bone marrow-derived MSCs.

PMID- 23541807
TI  - ErbB3 silencing reduces osteosarcoma cell proliferation and tumor growth in vivo.
AB  - Osteosarcoma is the most common primary bone tumor in children and adults.
      Despite improved prognosis, resistance to chemotherapy remains responsible for
      failure of osteosarcoma treatment. The identification of the molecular signals
      that contribute to the aberrant osteosarcoma cell growth may provide clues to
      develop new therapeutic strategies for chemoresistant osteosarcoma. Here we show
      that the expression of ErbB3 is increased in human osteosarcoma cells in vitro.
      Tissue microarray analysis of tissue cores from osteosarcoma patients further
      showed that the ErbB3 protein expression is higher in bone tumors compared to
      normal bone tissue, and is further increased in patients with recurrent disease
      or soft tissue metastasis. In murine osteosarcoma cells, silencing ErbB3 using
      shRNA decreased cell replication, cell migration and invasion, indicating that
      ErbB3 contributes to tumor cell growth and invasiveness. Furthermore, ErbB3
      silencing markedly reduced tumor growth in a murine allograft model in vivo.
      Immunohistochemal analysis showed that the reduced tumor growth induced by ErbB3
      silencing in this model resulted from decreased cell osteosarcoma cell
      proliferation, supporting a role of ErbB3 in bone tumor growth in vivo. Taken
      together, the results reveal that ErbB3 expression in human osteosarcoma
      correlates with tumor grade. Furthermore, silencing ErbB3 in a murine
      osteosarcoma model results in decreased cell growth and invasiveness in vitro,
      and reduced tumor growth in vivo, which supports the potential therapeutic
      interest of targeting ErbB3 in osteosarcoma.

PMID- 23541808
TI  - [Intraabdominal desmoid tumors in familial adenomatous polyposis].
AB  - Desmoid tumors are currently the main cause of morbidity and mortality in
      patients with familial adenomatous polyposis. More than 10% of these patients
      will develop these tumors during their lifetime and more than a third will suffer
      their consequences. The main risk factors for their development are female sex
      and abdominal surgery. The most frequent localization is intraabdominal. The
      therapeutic approach to these tumors has changed, and the surgical treatment of
      choice is currently the subject of debate. If a watch and wait approach is
      adopted, more than 50% of tumors will prove to be indolent. Therefore, the
      therapeutic strategy should be based on clinical presentation and should be
      decided by a multidisciplinary team working in a center with experience of these
      tumors. The present article proposes a prognostic classification to guide the
      therapeutic approach. 

PMID- 23541809
TI  - A model to estimate the risk of breast cancer-related lymphedema: combinations of
      treatment-related factors of the number of dissected axillary nodes, adjuvant
      chemotherapy, and radiation therapy.
AB  - PURPOSE: The development of breast cancer-related lymphedema (LE) is closely
      related to the number of dissected axillary lymph nodes (N-ALNs), chemotherapy,
      and radiation therapy. In this study, we attempted to estimate the risk of LE
      based on combinations of these treatment-related factors. METHODS AND MATERIALS:
      A total of 772 patients with breast cancer, who underwent primary surgery with
      axillary lymph node dissection from 2004 to 2009, were retrospectively analyzed.
      Adjuvant chemotherapy (ACT) was performed in 677 patients (88%). Among patients
      who received radiation therapy (n=675), 274 (35%) received supraclavicular
      radiation therapy (SCRT). RESULTS: At a median follow-up of 5.1 years (range, 3.0
      8.3 years), 127 patients had developed LE. The overall 5-year cumulative
      incidence of LE was 17%. Among the 127 affected patients, LE occurred within 2
      years after surgery in 97 (76%) and within 3 years in 115 (91%) patients.
      Multivariate analysis showed that N-ALN (hazard ratio [HR], 2.81; P<.001), ACT
      (HR, 4.14; P=.048), and SCRT (HR, 3.24; P<.001) were independent risk factors for
      LE. The total number of risk factors correlated well with the incidence of LE.
      Patients with no risk or 1 risk factor showed a significantly lower 5-year
      probability of LE (3%) than patients with 2 (19%) or 3 risk factors (38%)
      (P<.001). CONCLUSIONS: The risk factors associated with LE were N-ALN, ACT, and
      SCRT. A simple model using combinations of these factors may help clinicians
      predict the risk of LE.

PMID- 23541811
TI  - Low-intensity ultrasound accelerates mandibular implant bone integration in dogs
      with mandibular osteoradionecrosis.
AB  - BACKGROUND: To investigate whether low-intensity ultrasound accelerates healing
      in bone tissues close to dental implants with osteoradionecrosis (ORN) of the
      mandible and is suitable for development as a therapy in patients with dental
      implants receiving radiotherapy. MATERIALS AND METHODS: Dog models of radiative
      bone injury surrounding dental implants in both sides of mandible were
      established by four treatment methods of radiotherapy, each 15Gy. After radiative
      treatment, antibiotics were administered and the left injury was treated with
      ultrasound and the right with debridement. Measures for evaluation included
      spiral computed tomography (SCT), Micro-CT, microvessel density, and pull-out
      experiment, and data were collected and analyzed. RESULTS: After 4months of
      radiotherapy, both sides of mandible displayed preclinic symptom of radiative
      osteonecrosis. Microvessel density of the side treated by ultrasound was 6.2152+/
      0.6508 and that of the debridement side was 3.8490+/-0.8954 (P<0.05). Micro-CT
      results showed that bone volume fraction of trabecula, thickness of trabecula,
      trabecula spacing, ratio of bone surface area to bone volume, and trabecula
      number of the ultrasound-treated mandible were 0.3605+/-0.0337, 0.0287+/-0.0045,
      0.0369+/-0.0073, 71.6124+/-14.1649, and 7.2915+/-1.4937, whereas those of the
      debridement side were 0.1779+/-0.0178, 0.0151+/-0.0021, 0.6623+/-0.1125,
      33.2686+/-5.949, and 5.0689+/-0.5028, respectively; statistical significance was
      observed (P<0.05). Pull-out experiment suggested that pull-out strength of the
      ultrasound-treated side was 0.5793+/-0.1066 whereas that of the debridement side
      was 0.2980+/-0.0243, representing a statistical significance (P<0.05).
      CONCLUSIONS: Low-intensity ultrasound can accelerate the healing of bone tissues
      surrounding dental implants in osteoradionecrosis of the mandible animals.

PMID- 23541810
TI  - Sunitinib plus androgen deprivation and radiation therapy for patients with
      localized high-risk prostate cancer: results from a multi-institutional phase 1
      study.
AB  - PURPOSE: To evaluate the feasibility of administering sunitinib in combination
      with androgen deprivation therapy and external-beam intensity modulated radiation
      therapy (XRT) in patients with localized high-risk prostate cancer. METHODS AND
      MATERIALS: Seventeen men with localized adenocarcinoma of the prostate with cT2c
      cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial
      androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50
      mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4
      weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42
      fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation
      design was used to assess the frequency of dose-limiting toxicity (DLT) and
      establish a maximal tolerated dose of sunitinib. RESULTS: Sunitinib at 12.5- and
      25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg
      experienced a DLT during lead-in, and a drug interaction between sunitinib and
      bicalutamide was suspected. The protocol was revised and concurrent bicalutamide
      omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent
      therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3
      proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg
      daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25
      mg as reduced dose) completed therapy. CONCLUSIONS: The feasibility of combined
      vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth
      factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation
      therapy for prostate cancer was established. Using a daily dosing regimen with
      lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of
      sunitinib is 25 mg daily.

PMID- 23541812
TI  - Injection and adhesion palatoplasty: a preliminary study in a canine model.
AB  - BACKGROUND: Raising mucoperiosteal flaps in traditional palatoplasty impairs mid
      facial growth. Hyaluronic acid-based hydrogels have been successfully tested for
      minimally invasive craniofacial bone generation in vivo as carriers of bone
      morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique
      for cleft palate repair by injecting a BMP-2 containing hydrogel. MATERIAL AND
      METHODS: Dog pups with congenital cleft palate were either non-treated (n=4) or
      treated with two-flap palatoplasty (n=6) or with the proposed injection/adhesion
      technique (n=5). The experimental approach was to inject a hyaluronic acid-based
      hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate
      margins of pups aged six weeks. At week ten, a thin strip of the medial edge
      mucosa was removed and the margins were closed directly. Occlusal photographs and
      computed tomography (CT) scans were obtained up to week 20. RESULTS: Four weeks
      after the gel injection the cleft palate margins had reached the midline and
      engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa
      and suturing allowed complete closure of the cleft. Compared to traditional
      palatoplasty, the injection/adhesion technique was easier, and the post-surgical
      recovery was faster. CT on week 20 revealed some overlapping or "bending" of
      palatal shelves in the two-flap repair group, which was not observed in the
      experimental nor control groups. CONCLUSION: A minimally invasive technique for
      cleft palate repair upon injectable scaffolds in a dog model of congenital cleft
      palate is feasible. Results suggest better growth of palatal bones. This
      represents an attractive clinical alternative to traditional palatoplasty for
      cleft palate patients.

PMID- 23541813
TI  - The rare sugar D-allose has a reducing effect against ischemia-reperfusion injury
      on the rat abdominal skin island flap model.
AB  - BACKGROUND: Recently, one of the rare sugars, D-allose, has received attention
      from many researchers because of its availability for mass production and its
      various physiological functions. Among these, an antioxidative effect has been
      strongly suggested. In this study, we investigated whether this effect is also
      applicable to the field of skin surgery. METHODS: In ischemia-reperfusion injury
      model using the rat abdominal skin island flap (male Wistar rats, n = 110), D
      allose was injected intravenously 15 min before 8-h ischemia. The survival area
      (%) was measured by digital photographic assessment 1 wk after surgery, and
      multiple comparisons (Fisher's protected least significant difference) were
      carried out. Histopathological examination (neutrophilic infiltration into dermis
      in hematoxylin and eosin stain) and immunostaining (of ectodermal dysplasia-1
      (ED1)-positive cells/flap) were assessed. Myeloperoxidase (MPO) activity in the
      skin flap (sampling at the time of 8 h after reperfusion) was measured
      spectrophotometrically, and Student t-test was performed. RESULTS: D-allose
      extended the survival of the remaining flaps, and a dose greater than 30 mg (0.1
      mg/g) was necessary to be effective. The flap survival rates in the 30, 60, and
      150 mg groups were significantly higher than that in the control (saline) group:
      75.87 +/- 5.90, 79.27 +/- 7.81, and 77.87 +/- 6.20 versus 50.53 +/- 9.66,
      respectively (P < 0.05). ED1-positive cells/flap in 60 mg of D-allose and control
      (saline) were 78 +/- 25.7 versus 124 +/- 15.8, respectively (P = 0.08). The MPO
      activity in the D-allose 60 mg group was 0.40 +/- 0.04, and that in the control
      (saline) was 0.72 +/- 0.12. D-allose significantly reduced the skin tissue MPO
      activity (P < 0.05) compared with that in the control (saline) group.
      CONCLUSIONS: We proved that D-allose has a reducing effect against ischemia
      reperfusion injury on the skin island flap model, and the mechanism is related to
      inhibiting the activity of neutrophils in the skin tissues. Compared with chemo
      synthetic materials, rare sugars are safer for our bodies as well as the
      environment; therefore, this rare sugar project is expected to lead to the
      development of a safer antioxidant for skin flap surgery.

PMID- 23541814
TI  - A pilot study of the use of kaolin-impregnated gauze (Combat Gauze) for packing
      high-grade hepatic injuries in a hypothermic coagulopathic swine model.
AB  - BACKGROUND: Severe hepatic injuries may be highly lethal, and perihepatic packing
      remains the mainstay of treatment. This is not always successful, particularly in
      the setting of hypothermia and coagulopathy. Kaolin-impregnated Combat Gauze (CG)
      is an effective hemostatic dressing used primarily to treat external wounds. The
      objective of this study was to determine the ability of CG to control severe
      hemorrhage in hypothermic, coagulopathic swine with a high-grade hepatic injury.
      METHODS: Anesthetized animals underwent splenectomy and were cooled to 32 degrees
      C while undergoing a 60% exchange transfusion with Hextend. A grade V liver
      injury was created in the left middle hepatic lobe. Animals were allowed to
      freely bleed for 30 s and then randomized to treatment with CG or plain gauze
      laparotomy pads (PG) applied to the injury site. Animals were then resuscitated
      with warmed Hextend. RESULTS: There was no difference between groups in preinjury
      hemodynamic or laboratory values. Animals packed with CG had less blood loss when
      compared with standard packing (CG = 25 mL/kg versus PG = 58 mL/kg, P = 0.05).
      There was a trend towards lower hetastarch resuscitation requirements in the CG
      group (CG = 7 mL/kg versus PG = 44 mL/kg, P = 0.06) but no statistically
      significant difference in mortality (CG = 13% versus PG = 50%, P = 0.11).
      Histology of the injury sites revealed more adherent clot in the CG group, but no
      inflammation, tissue necrosis, or residual material. CONCLUSION: In pigs with
      severe hepatic injury, Combat Gauze reduced blood loss and resuscitation
      requirements when compared with plain laparotomy pads. Combat Gauze may be safe
      and effective for use on severe liver injuries.

PMID- 23541815
TI  - Quantitative quenching evaluation and direct intracellular metabolite analysis in
      Penicillium chrysogenum.
AB  - Sustained progress in metabolic engineering methodologies has stimulated new
      efforts toward optimizing fungal production strains such as through metabolite
      analysis of Penicillium chrysogenum industrial-scale processes. Accurate
      intracellular metabolite quantification requires sampling procedures that rapidly
      stop metabolism (quenching) and avoid metabolite loss via the cell membrane
      (leakage). When sampling protocols are validated, the quenching efficiency is
      generally not quantitatively assessed. For fungal metabolomics, quantitative
      biomass separation using centrifugation is a further challenge. In this study, P.
      chrysogenum intracellular metabolites were quantified directly from biomass
      extracts using automated sampling and fast filtration. A master/slave bioreactor
      concept was applied to provide industrial production conditions. Metabolic
      activity during sampling was monitored by 13C tracing. Enzyme activities were
      efficiently stopped and metabolite leakage was absent. This work provides a
      reliable method for P. chrysogenum metabolomics and will be an essential base for
      metabolic engineering of industrial processes.

PMID- 23541816
TI  - [Vacuum assisted closure therapy in dehiscence of abdominal wound after cesarean
      section treated in a hospital-at-home].
AB  - The Hospital at Home is a range of hospital care provided to patients in the
      comfort of their own homes, so patient and family can actively participate in the
      process. Cesarean section is a surgical procedure that requires a short hospital
      stay. However if complications arise during the process, such as a dehiscence of
      surgical wound, the hospital stay is prolonged, delaying mother-child bonding,
      which is very important for the growth of the child. Nursing care in wound
      healing by secondary intention is a priority for the patient's recovery. VAC
      therapy (vacuum assisted closure) promotes a rapid recovery, although it requires
      dressings and active medical surveillance, as well as training by the nursing
      staff for carrying it out at home. We describe the outcome and the process of the
      healing of a surgical wound after cesarean section, not only because of a complex
      wound, but the previously mentioned factors that make us consider the Hospital at
      Home as the best alternative care.

PMID- 23541817
TI  - [Nursing in the world to come].

PMID- 23541818
TI  - [Mortality in patients with acute respiratory failure on chronic treatment with
      benzodiazepines].
AB  - The benzodiazepines (BZD) are among the drugs most used by the population. Its
      contraindications include severe respiratory failure and sleep apnoea. The main
      objective of this work was to establish the relationship between the chronic use
      of benzodiazepines and hospital mortality and up to 30 days after admission. This
      study was carried out on a retrospective cohort of 243 patients admitted via
      emergency room into "Reina Sofia" University General Hospital in Murcia during
      the year 2011, and were selected for having been treated with non-invasive
      mechanical ventilation (NIV) during their admission. The method used was a review
      of clinical histories by searching for the code corresponding to the NIV process.
      Overall mortality was 20.6%. In patients with chronic consumption of BZD it was
      22.45% and 19.4% in patients who did not use these drugs (P=.608). We were unable
      to establish a significant relationship between chronic use of benzodiazepines
      and overall mortality figures. On the other hand, we have linked the increased
      mortality in patients treated with NIV for acute respiratory failure with other
      indicators such as, age above 75 years old, blood bicarbonate below 22mmol/L;
      lactic acid higher than 2mmol/L; serum creatinine above 1.5mg/dL, and sepsis. 

PMID- 23541819
TI  - [Characteristics of use of an out-of-hospital emergency medical service by
      children].
AB  - OBJECTIVES: To quantify and to describe the characteristics of use of an
      Emergency Medical Service by children in Bilbao City (Spain). PATIENTS AND
      METHODS: An observational and retrospective study was performed taking patients
      younger than 15 years old who were served by Basic Life Support Units from an
      Emergency Medical Service for 4 consecutive years (2008-2011). RESULTS: 525
      interventions were registered (anual range 102-155 interventions), which
      represented 2.25% of total services. 54.5% (p<0,001) of patients were male. The
      mean age was 7.6 years old (95% CI 6.8 to 7.5). The causes of action were
      associated to accidental causes in 49.1% of cases and disease in 50.9% (p=0,44),
      with a predominance of injuries in the 5 to 9 years (p<0,001) and disease among
      children under 5 years (p<0,001). The main disorders observed were injuries
      (41.9%), convulsive episodes (17.1%) and respiratory symptoms (10.3%). 78.9% need
      to transfer to health care center. CONCLUSIONS: The volume of pediatric care
      carried out between 2008 and 2011 has not changed annually. The main visits were
      due to traumas and convulsions. Most emergency situations are not resolved on the
      spot, being necessary to transfer to hospital.

PMID- 23541820
TI  - [Cocaine abuse and multiple use of psychoactive substances in university
      students].
AB  - OBJECTIVES: To identify the prevalence of cocaine consumption among university
      students and to analyse the use of other drugs among the regular cocaine
      consumers. METHOD: An observational, descriptive and cross-sectional study
      performed within the Education, Sciences and Psychology Faculties and the Nursing
      and Polytechnic Schools belonging to the University of Girona. The selected
      sample included 2139 first year university students. A self-constructed
      questionnaire was used to obtain the information regarding gender, age, Faculty,
      and the status of consume. RESULTS: The participants were 47.2% males and 52.8%
      females, with an age range between 17 and 35 years old (median=21 years,
      SD=3.14). One per-cent of the participants considered themselves usual cocaine
      consumers. Nine out of every 10 students also use alcohol (95.2%) and cannabis
      (90.5%). CONCLUSIONS: It has been shown that university students have health
      threatening habits, such as cocaine abuse. It is more common the use of other
      drugs among cocaine users than among non-consumers. Preventive and educational
      programs at the university may be required to reduce and prevent toxic substances
      abuse among university students.

PMID- 23541821
TI  - [Effectiveness of a nursing in-home intervention to improve independence in
      adls/iadls and family burden in adults with schizophrenia].

PMID- 23541822
TI  - Adaptive Neuromorphic Architecture (ANA).
AB  - We designed Adaptive Neuromorphic Architecture (ANA) that self-adjusts its
      inherent parameters (for instance, the resonant frequency) naturally following
      the stimuli frequency. Such an architecture is required for brain-like engineered
      systems because some parameters of the stimuli (for instance, the stimuli
      frequency) are not known in advance. Such adaptivity comes from a circuit element
      with memory, namely mem-inductor or mem-capacitor (memristor's sisters), which is
      history-dependent in its behavior. As a hardware model of biological systems, ANA
      can be used to adaptively reproduce the observed biological phenomena in amoebae.

PMID- 23541823
TI  - The clinical consequences of an ageing world and preventive strategies.
AB  - Over the past century, the world has seen unprecedented declines in mortality
      rates, leading to an accelerated increase in the world population. This century
      will realise falling fertility rates alongside ageing populations. The 20th
      century was the century of population growth; the 21st century will be remembered
      as the century of ageing. Increase in life expectancy is one of the highest
      achievements of humankind; however, ageing and age-related disease is a mounting
      challenge for individuals, families, and for social, economic, and healthcare
      systems. Since healthy life expectancy has lagged behind the increase in life
      expectancy, the rise in morbidity will increase the burden on healthcare systems.
      Implementation of preventive health strategies to decrease, delay or prevent
      frailty, lung, breast and colon cancer, cardiovascular disease, metabolic
      syndrome, osteoporosis and osteopaenia, may increase health expectancy, and
      permit women to age gracefully and maintain independent living, without
      disability, for as long as possible. 

PMID- 23541824
TI  - The use of 14C-FIAU to predict bacterial thymidine kinase presence: implications
      for radiolabeled FIAU bacterial imaging.
AB  - Currently available infectious disease imaging techniques cannot differentiate
      between infection and sterile inflammation or between different types of
      infections. Recently, radiolabeled FIAU was found to be a substrate for the
      thymidine kinase (TK) enzyme of multiple pathogenic bacteria, leading to its
      translational use in the imaging of bacterial infections. Patients with
      immunodeficiencies, however, are susceptible to a different group of pathogenic
      bacteria when compared to immunocompetent subjects. In this study, we wanted to
      predict the usefulness of radiolabeled FIAU in the detection of bacterial
      infections commonly occurring in patients with immunodeficiencies, in vitro,
      prior to attempting in vivo imaging with (124)I-FIAU-PET. METHODS: We obtained
      representative strains of bacterial pathogens isolated from actual patients with
      genetic immunodeficiencies. We evaluated the bacterial susceptibility of
      different strains to the effect of incubation with FIAU, which would implicate
      the presence of the thymidine kinase (TK) enzyme. We also incubated the bacteria
      with (14)C-FIAU and consequently measured its rate of incorporation in the
      bacterial DNA using a liquid scintillation counter. RESULTS: Unlike the other
      bacterial strains, the growth of Pseudomonas aeruginosa was not halted by FIAU at
      any concentration. All the tested clinical isolates demonstrated different levels
      of (14)C-FIAU uptake, except for P. aeruginosa. CONCLUSION: Radiolabeled FIAU has
      been successful in delineating bacterial infections, both in preclinical and
      pilot translational studies. In patients with immunodeficiencies, Pseudomonas
      infections are commonly encountered and are usually difficult to differentiate
      from fungal infections. The use of radiolabeled FIAU for in vivo imaging of those
      patients, however, would not be useful, considering the apparent lack of TK
      enzyme in Pseudomonas. One has to keep in mind that not all pathogenic bacteria
      possess the TK enzyme and as such will not all retain FIAU. Our technique is
      simple, and can be easily used to assess whether a certain bacterial strain of
      interest can or cannot be visualized using radiolabeled FIAU.

PMID- 23541825
TI  - Palladium mediated 11C-cyanation and characterization in the non-human primate
      brain of the novel mGluR5 radioligand [11C]AZD9272.
AB  - INTRODUCTION: The aims of the present positron emission tomography (PET) study
      were to set up a system for (11)C-cyanation labeling of the selective mGluR5
      antagonist [(11)C]AZD9272 and to perform the first in vivo characterization of
      [(11)C]AZD9272 binding in cynomolgus monkeys. METHODS: [(11)C]AZD9272 was labeled
      using palladium mediated (11)C-cyanation. Altogether seven PET measurements were
      performed in three cynomolgus monkeys including baseline and co-injection
      experiments with unlabelled AZD9272 (0.04 and 0.4 mg/kg). Radiometabolites in
      plasma were measured using HPLC. RESULTS: [(11)C]AZD9272 was prepared in over 50%
      incorporation yield from hydrogen [(11)C]cyanide in a total synthesis time of 45
      50 min. The radiochemical purity of the radioligand in its final formulation was
      high (>99%) and the mean specific radioactivity was 47 GBq/ MUmol (1278 Ci/mmol,
      n=7) calculated at end of bombardment (EOB). In the baseline measurements 10% of
      the total injected radioactivity was present in monkey brain at five minutes
      after i.v. injection. The radioactivity concentration was high in the caudate,
      cingulate gyrus and thalamus whereas it was moderate in the temporal cortex and
      lower for the cerebellum. After co-injection with cold AZD9272 the binding of
      [(11)C]AZD9272 was reduced in a dose-dependent fashion. Analysis of
      radiometabolites showed relatively slow metabolism and resulted only in
      hydrophilic radiometabolites. CONCLUSION: A fast and efficient method was
      developed to label AZD9272 with (11)C. PET-examination in Cynomolgus monkeys
      showed that [(11)C]AZD9272 entered the brain to a high extent, that binding was
      saturable and that the regional radioactivity pattern was in accordance with the
      known distribution of mGluR5. The results support further examination of
      [(11)C]AZD9272 binding in human subjects.

PMID- 23541826
TI  - Can rats control previously acquired spatial information? Evidence of "directed
      forgetting" phenomenon in delay-interposed radial maze behavior.
AB  - "Directed forgetting" is a method and a phenomenon used to investigate whether
      organisms can control memory with instructions to forget, and to remember. We
      examined directed forgetting phenomenon in rats, using a modified radial maze
      task. In the delay-interposed radial maze task, a 120-min delay followed four
      correct choices, during which rats were placed in either a white or black box,
      that signaled whether a second-half performance will be required (remember (R)
      trial), or not (forget (F)-trial) after the delay. R- and F-trials were repeated
      5 times each, followed by a "probe test," in which the second-half performance
      was conducted, although the F-cue was presented during the delay period. Rats
      made more errors in the probe test than in the R-trial. These results demonstrate
      the "directed forgetting" phenomenon in a radial maze task in rats, and suggest
      that rats can indeed control previously acquired spatial information, even
      situations with a long retention interval interposed. Although the mechanism by
      which presentation of the "forget-cue" influences rats' information processing
      remains unclear, several brain regions, including the medial prefrontal cortex
      and the hippocampal CA3 area, were shown to be more activated in the "remember"
      cued trial than in the "forget"-cued trial, suggesting that these areas are
      potentially related to the "directed forgetting" phenomenon of spatial
      information demonstrated in the study.

PMID- 23541827
TI  - Imaging of abdominal complications associated with hematopoietic stem cell
      transplantation.
AB  - Complications associated with hematopoietic stem cell transplantation are common
      and frequently involve the gastrointestinal tract and other abdominal organs.
      Imaging is often used to help to confirm or exclude a suspected complication and
      to facilitate management. In this article, we review the imaging findings of
      abdominal complications related to hematopoietic stem cell transplantation.

PMID- 23541828
TI  - Computed tomography imaging of the acute pelvis in females.
AB  - Sonography is the primary imaging modality for the evaluation of pelvic pain in
      female patients, especially if gynaecological pathology is suspected. However,
      computed tomography (CT) is frequently used in patients who present to emergency
      departments (and elsewhere) with otherwise nonspecific abdominal and pelvic pain
      and may be the first imaging modality to demonstrate an acute gynaecological
      abnormality. Computed tomography can also be used prospectively in selected
      patients to further evaluate findings initially identified on sonography,
      although to reduce radiation exposure, magnetic resonance imaging is being used
      more frequently in this situation. The purpose of this article is to discuss the
      spectrum of gynaecological findings of the acute female pelvis that may be
      identified on CT by the emergency radiologist and by the general radiologist,
      with a brief review of the imaging literature of each specific diagnosis.

PMID- 23541829
TI  - Review of multidetector computed tomography angiography as a screening modality
      in the assessment of blunt vascular neck injuries.
AB  - Blunt vascular neck injuries (BVNI), previously thought to be rare, have
      demonstrated increasing incidence rates in recent literature and are associated
      with significant mortality and morbidity. A radiologist needs to efficiently
      recognize these injuries on preliminary screening to enable initiation of early
      management. When initiation of accurate management is started promptly, decreased
      rates of postinjury complications, for example, stroke, have been demonstrated.
      This article reviews the incidence, pathophysiology, and rationale for screening
      for these BVNI injuries. The utility of computed tomography angiography (CTA) as
      the potential new criterion standard as the screening and follow-up imaging
      modality for BVNI will be discussed. The application of new multidetector CTA
      techniques available, such as dual-energy CT and iterative reconstruction, are
      also reviewed. In addition, the characteristic imaging findings on CTA and the
      associated Denver Grading scale for BVNI will be reviewed to allow readers to
      become familiar with the injury patterns and to understand the prognostic and
      clinical implications, respectively. Examples of the spectrum of injuries,
      potential injury mimics, and different artifacts on multidetector CTA are shown
      to help familiarize readers and allow them to successfully and confidently
      recognize a true BVNI.

PMID- 23541830
TI  - Controlling the number of melanopsin-containing retinal ganglion cells by early
      light exposure.
AB  - A small percentage of retinal ganglion cells (RGCs) express melanopsin and are
      intrinsically photosensitive (ipRGCs). Whether light can affect the development
      of ipRGCs is not clear. In the rat retina, we found constant light exposure
      during the first postnatal week significantly increased the number of melanopsin
      immunopositive ipRGCs. This increase was durable and specific for melanopsin
      immunopositive ipRGCs. BrdU labeling showed no proliferation of the melanopsin
      immunopositive ipRGCs during constant light exposure. Retrograde labeling from
      the superior colliculus showed that no other types of RGCs were induced to
      express melanopsin. Light exposure was effective in increasing melanopsin
      immunopositive ipRGCs only when it coincided with the apoptotic phase of RGC
      development. However, daily intravitreous injection of tetrodotoxin, blocking
      action potentials, abolished the light induced increase of melanopsin
      immunopositive ipRGCs. These findings indicate that early light exposure can
      increase the number of melanopsin immunopositive ipRGCs through a process
      dependent on intrinsic photosensitive spiking activity. Furthermore, the increase
      of melanopsin immunopositive ipRGCs is potentially induced by apoptosis
      suppression in ipRGCs or enhanced expression of melanopsin.

PMID- 23541831
TI  - Distribution of thrombospondins and their neuronal receptor alpha2delta1 in the
      rat retina.
AB  - The role of the extracellular matrix protein thrombospondins (TSPs) in promoting
      synaptogenesis is gaining more and more attention. The binding of TSP1 and TSP2
      to their neuronal receptor alpha2delta1 stimulates excitatory synaptogenesis in
      the development and injury of the central nervous system; however, the specific
      cellular localization and expression of TSP1/2 and alpha2delta1 in healthy and
      damaged retinas is unknown. This, to a certain extent, has restricted the
      progress of research on the molecular mechanisms triggering synaptic plasticity
      after retinal injury. Here, the cellular localization and expression of TSP1/2
      and their receptor alpha2delta1 was studied in healthy and damaged adult retina
      induced by elevated intraocular pressure (IOP) using double immunofluorescence
      labeling and confocal scanning microscopy. We showed the apparent differential
      distribution of TSP1 and TSP2 in the adult rat retina. TSP1 was confined to the
      ganglion cell layer and inner nuclear layer, in which it was preferentially
      expressed by ganglion cells, bipolar cells and horizontal cells but rarely
      expressed by glial cells. TSP2 staining was diffusely distributed in GFAP- and GS
      immunopositive glial cells and processes in the inner retina. In rat retinas,
      alpha2delta1 staining was present in ganglion cells, bipolar cells, partial
      horizontal cells and amacrine cells and the presynaptic terminals. Muller cells
      and a minority of astrocytes also expressed alpha2delta1. On the seventh day of
      elevated IOP, TSP2 immunoreactivity was greatly increased, and immunopositive
      processes extended throughout the retinal layer and co-localized with GFAP- and
      GS-positive glial cells. TSP1 distribution in the retina, however, did not change
      distinctly. alpha2delta1-immunopositive processes were also increased on the
      seventh day after elevated IOP. Our study suggested that in the adult rat retina,
      TSP2, but not TSP1, secreted by glial cells may be involved in the synaptic
      plastic process after retinal injury through binding to its neuronal receptor
      alpha2delta1.

PMID- 23541832
TI  - FOXC1 in human trabecular meshwork cells is involved in regulatory pathway that
      includes miR-204, MEIS2, and ITGbeta1.
AB  - Forkhead box C1 (FOXC1) is a transcription factor that affects eye development.
      FOXC1 is implicated in the etiology of glaucoma because mutations in the gene are
      among the causes of Axenfeld-Rieger syndrome which is often accompanied by
      glaucoma. Glaucoma is the second leading cause of blindness. It is a complex
      disorder whose genetic basis in most patients remains unknown. Microarrays
      expression analysis was performed to identify genes in human trabecular meshwork
      (TM) primary cultures that are affected by FOXC1 and genes that may have roles in
      glaucoma. This represents the first genome wide analysis of FOXC1 target genes in
      any tissue. FOXC1 knock down by siRNAs affected the expression of 849 genes.
      Results on selected genes were confirmed by real time PCR, immunoblotting, and
      dual luciferase reporter assays. Observation of MEIS2 as a FOXC1 target and
      consideration of FOXC1 as a potential target of miR-204 prompted testing the
      effect of this micro RNA on expression of FOXC1 and several genes identified by
      array analysis as FOXC1 target genes. It was observed that miR-204 caused
      decreased expression of FOXC1 and the FOXC1 target genes CLOCK, PLEKHG5,
      ITGbeta1, and MEIS2 in the TM cultures. Expression of CLOCK, PLEKHG5, ITGbeta1
      has not previously been reported to be affected by miR-204. The data suggest
      existence of a complex regulatory pathway in the TM part of which includes
      interactions between FOXC1, miR-204, MEIS2, and ITGbeta1. All these molecules are
      known to have TM relevant functions, and the TM is strongly implicated in the
      etiology of glaucoma.

PMID- 23541833
TI  - Synthesis of (S)-FTY720 vinylphosphonate analogues and evaluation of their
      potential as sphingosine kinase 1 inhibitors and activators.
AB  - Sphingosine kinase 1 (SK1) is over-expressed in many cancers where it provides a
      selective growth and survival advantage to these cells. SK1 is thus a target for
      anti-cancer agents that can promote apoptosis of cancer cells. In previous work,
      we synthesized a novel allosteric SK1 inhibitor, (S)-FTY720 vinylphosphonate. We
      now report a more expeditious route to this inhibitor which features B-alkyl
      Suzuki coupling as a key step and show that replacement of the amino group in (S)
      FTY720 vinylphosphonate with an azido group converts the vinylphosphonate from an
      allosteric inhibitor to an activator of SK1 at low micromolar concentrations. Our
      results demonstrate the feasibility of using the (S)-FTY720 vinylphosphonate
      scaffold to define structure-activity relationships in the allosteric site of
      SK1.

PMID- 23541834
TI  - Synthesis and biological evaluation of novel azole derivatives as selective
      potent inhibitors of brassinosteroid biosynthesis.
AB  - Brassinosteroids (BRs) are phytohormones that control several important agronomic
      traits, such as flowering, plant architecture, seed yield, and stress tolerance.
      To manipulate the BR levels in plant tissues using specific inhibitors of BR
      biosynthesis, a series of novel azole derivatives were synthesized and their
      inhibitory activity on BR biosynthesis was investigated. Structure-activity
      relationship studies revealed that 2RS, 4RS-1-[4-(2-allyloxyphenoxymethyl)-2-(4
      chlorophenyl)-[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4]triazole (G(2)) is a highly
      selective inhibitor of BR biosynthesis, with an IC(50) value of approximately 46
      +/- 2 nM, which is the most potent BR biosynthesis inhibitor observed to date.
      Use of gibberellin (GA) biosynthesis mutants and BR signaling mutants to analyze
      the mechanism of action of this synthetic series indicated that the primary site
      of action is BR biosynthesis. Experiments feeding BR biosynthesis intermediates
      to chemically treated Arabidopsis seedlings suggested that the target sites of
      this synthetic series are CYP90s, which are responsible for the C-22 and/or C-23
      hydroxylation of campesterol.

PMID- 23541835
TI  - Discovery of aryl-biphenyl-2-ylmethylpiperazines as novel scaffolds for 5-HT(7)
      ligands and role of the aromatic substituents in binding to the target receptor.
AB  - It has been reported that 5-HT(7) receptors are promising targets of depression
      and neuropathic pain. 5-HT(7) receptor antagonists have exhibited antidepressant
      like profiles, while agonists have represented potential therapeutics for pain.
      In the course of our ongoing efforts to discover novel 5-HT(7) modulators, we
      designed an arylpiperazine scaffold with a substituted biphenyl-2-ylmethyl group.
      A series of biphenyl-2-yl-arylpiperazinylmethanes were then prepared, which
      showed a broad spectrum of binding affinities to the 5-HT(7) receptor depending
      upon the substituents attached to the biphenyl and aryl functionalities. Among
      those synthesized compounds, the compounds 1-24 and 1-26 showed the best binding
      affinities to the 5-HT(7) receptor with K(i) values of 43.0 and 46.0 nM,
      respectively. Structure-activity relationship study in conjunction with molecular
      docking study proposed that the 5-HT(7) receptor might have two distinctive
      hydrophobic binding sites, one specific for aromatic 2-OCH(3) substituents within
      the arylpiperazine and the other for biphenyl methoxy group.

PMID- 23541836
TI  - Design, synthesis and evaluation of tacrine-flurbiprofen-nitrate trihybrids as
      novel anti-Alzheimer's disease agents.
AB  - To search for multifunctional anti-Alzheimer's disease (AD) agents with good
      safety, the previously synthesized tacrine-flurbiprofen hybrids 1a and 1b were
      modified into tacrine-flurbiprofen-nitrate trihybrids 3a-h. These compounds
      displayed comparable or higher cholinesterase inhibitory activity relative to the
      bivalent hybrids. Compound 3a was the most potent, which released moderate NO,
      exerted blood vessel relaxative activity, and showed significant Abeta inhibitory
      effects whereas tacrine and flurbiprofen did not exhibit any Abeta inhibitory
      activity at the same dose. In addition, 3a was active in improving memory
      impairment in vivo. More importantly, the hepatotoxicity study showed that 3a was
      much safer than tacrine, suggesting it might be a promising anti-AD agent for
      further investigation.

PMID- 23541837
TI  - New repertoire of 'donor-two-acceptor' NIR fluorogenic dyes.
AB  - Dye molecules with various fluorescent wavelengths are widely used for diagnostic
      and optical imaging applications. Accordingly, there is a constant demand for
      fluorogenic dyes with new properties. We have recently developed a novel strategy
      for the design of long-wavelength fluorescent dyes with a turn-ON option. The
      design is based on a donor-two-acceptor pi-electron system that can undergo an
      internal charge transfer to form a new fluorochrome with an extended pi
      conjugated system. Here, we describe a series of such dyes based on two novel
      latent donors, naphthol and hydroxycoumarin. One of the dyes has showed excellent
      near-infrared fluorescent characteristics and specifically was demonstrated as a
      mitochondrial imaging reagent in live cells. This unique strategy for fluorogenic
      dye design has opened new doors for further near-infrared fluorescence probe
      discovery.

PMID- 23541838
TI  - Composition and interrelationships of a large Neotropical freshwater fish group,
      the subfamily Cheirodontinae (Characiformes: Characidae): a case study based on
      mitochondrial and nuclear DNA sequences.
AB  - Characidae is the most species-rich family of freshwater fishes in the order
      Characiformes, with more than 1000 valid species that correspond to approximately
      55% of the order. Few hypotheses about the composition and internal relationships
      within this family are available and most fail to reach an agreement. Among
      Characidae, Cheirodontinae is an emblematic group that includes 18 genera (1
      fossil) and approximately 60 described species distributed throughout the
      Neotropical region. The taxonomic and systematic history of Cheirodontinae is
      complex, and only two hypotheses about the internal relationships in this
      subfamily have been reported to date. In the present study, we test the
      composition and relationships of fishes assigned to Cheirodontinae based on a
      broad taxonomic sample that also includes some characid incertae sedis taxa that
      were previously considered to be part of Cheirodontinae. We present phylogenetic
      analyses of a large molecular dataset of mitochondrial and nuclear DNA sequences.
      Our results reject the monophyly of Cheirodontinae as previously conceived, as
      well as the tribes Cheirodontini and Compsurini, and the genera Cheirodon,
      Compsura, Leptagoniates, Macropsobrycon, Odontostilbe, and Serrapinnus. On the
      basis of these results we propose: (1) the exclusion of Amazonspinther and
      Spintherobolus from the subfamily Cheirodontinae since they are the sister-group
      of all remaining Characidae; (2) the removal of Macropsobrycon xinguensis of the
      genus Macropsobrycon; (3) the removal of Leptagoniates pi of the genus
      Leptagoniates; (4) the inclusion of Leptagoniates pi in the subfamily
      Cheirodontinae; (5) the removal of Cheirodon stenodon of the genus Cheirodon and
      its inclusion in the subfamily Cheirodontinae under a new genus name; (6) the
      need to revise the polyphyletic genera Compsura, Odontostilbe, and Serrapinnus;
      and (7) the division of Cheirodontinae in three newly defined monophyletic
      tribes: Cheirodontini, Compsurini, and Pseudocheirodontini. Our results suggest
      that our knowledge about the largest Neotropical fish family, Characidae, still
      is incipient.

PMID- 23541839
TI  - Multigene-based analyses on evolutionary phylogeny of two controversial ciliate
      orders: Pleuronematida and Loxocephalida (Protista, Ciliophora,
      Oligohymenophorea).
AB  - Relationships among members of the ciliate subclass Scuticociliatia (Ciliophora,
      Oligohymenophorea) are largely unresolved. Phylogenetic studies of its orders
      Pleuronematida and Loxocephalida were initially based on small subunit ribosomal
      RNA gene (SSU-rDNA) analyses of a limited number of taxa. Here we characterized
      37 sequences (SSU-rDNA, ITS-5.8S and LSU-rDNA) from 21 taxonomically
      controversial members of these orders. Phylogenetic trees constructed to assess
      the inter- and intra-generic relationships of pleuronematids and loxocephalids
      reveal the following: (1) the order Loxocephalida and its two families
      Loxocephalidae and Cinetochilidae are not monophyletic when more taxa are added;
      (2) the core pleuronematids are divided into two fully supported clades, however,
      the order Pleuronematida is not monophyletic because Cyclidium glaucoma is closer
      to Thigmotrichida; (3) the family Pleuronematidae and the genus Schizocalyptra
      are monophyletic, though rDNA sequences of Pleuronema species are highly
      variable; (4) Pseudoplatynematum and Sathrophilus are closely related to the
      subclass Astomatia, while Cinetochilum forms a monophyletic group with the
      subclass Apostomatia; and (5) Hippocomos falls in the order Pleuronematida and is
      closely related to Eurystomatellidae and Cyclidium plouneouri. Further, in an
      effort to provide a better resolution of evolutionary relationships, the
      secondary structures of ITS2 transcripts and the variable region 4 (V4) of the
      small subunit ribosomal RNA (SSU-rRNA) are predicted, revealing that ITS2
      structures are conserved at the order level while V4 region structures are more
      variable than ITS2 structures.

PMID- 23541840
TI  - Detection of HIV-1 minority variants containing the K103N drug-resistance
      mutation using a simple method to amplify RNA targets (SMART).
AB  - The simple method for amplifying RNA targets (SMART) was used to detect K103N, a
      common HIV-1 reverse transcriptase drug-resistance mutation. Novel amplifiable
      SMART probes served as reporter molecules for RNA sequences that are captured and
      separated on a microfluidic platform under zero-flow conditions. Assays were
      performed both off chip and in a microchip reservoir using a modified version of
      real-time nucleic acid sequence-based amplification, without the noncyclic phase,
      and 65 degrees C preheat. A total of 6000 copies/mL of the synthetic sequences
      were detected within 180 minutes of amplification. Although the sensitivity of
      research platforms is higher, SMART has the potential to offer comparable
      sensitivity and speed to commercially available viral load and HIV detection
      kits. Furthermore, SMART uses an inexpensive, practical, and more accurate
      isothermal exponential amplification technique. The use of molecular beacons
      resulted in relatively fast real-time detection (<180 minutes); however, they
      were also shown to hinder the amplification process when compared with end point
      detection. Finally, SMART probes were used for modeling of K103N concentrations
      within an unknown sample. Only 1% of the SMART probes was detected within the
      wild-type population (6 * 10(8) copies/mL). These results establish the
      groundwork for point-of-care drug resistance and viral load monitoring in
      clinical samples, which can revolutionize HIV patient care globally.

PMID- 23541841
TI  - Reference values for major depression questionnaires: the Leiden Routine Outcome
      Monitoring Study.
AB  - BACKGROUND: The Beck Depression Inventory-II (BDI-II), the Inventory of
      Depressive Symptoms (self-report) (IDS-SR) and the Montgomery-Asberg Depression
      Rating Scale (MADRS) are questionnaires that assess symptom severity in patients
      with a depressive disorder, often part of Routine Outcome Monitoring (ROM). We
      aimed to generate reference values for both "healthy" and "clinically depressed"
      populations. METHODS: We included 1295 subjects from the general population (ROM
      reference-group) recruited through general practitioners, and 4627 psychiatric
      outpatients diagnosed with Major Depressive Disorder (MDD) or dysthymia (ROM
      patient-group). The outermost 5% of observations were used to define limits for
      one-sided reference intervals (95th percentiles; P95). Receiver Operating
      Characteristics (ROC) analyses were used to yield alternative cut-off values.
      Internal consistency was assessed. RESULTS: The mean age was 40.3yr (SD=12.6) and
      39.3 (SD=12.3) for the ROM reference and patient-groups, respectively, and 62.8%
      versus 61.0% were female. Cut-off (P95) values differed for women and men, being
      respectively 15 and 12 for the BDI-II, 23 and 18 for the IDS-SR, and 12.5 and 9
      for the MADRS. ROC analyses yielded almost equal reference values. The
      discriminative power of the BDI-II, IDS-SR and MADRS scores was very high.
      Internal consistency was excellent for total scores and satisfactory for all
      subscales, except for the IDS-SR subscale Atypical Characteristics. LIMITATIONS:
      Substantial non-response and limited generalizability. CONCLUSIONS: For the BDI
      II, IDS-SR and MADRS a comprehensive set of reference values were provided.
      Reference values were higher in women than in men, implying the use of sex
      specific cut-off values. Either instrument can be offered to every patient with
      MAS disorders to make responsible decisions about continuing, changing or
      terminating therapy.

PMID- 23541842
TI  - Childhood emotional environment and self-injurious behaviors: the moderating role
      of the BDNF Val66Met polymorphism.
AB  - BACKGROUND: Previous theory has suggested that invalidating environments in the
      form of emotional maltreatment should be a specific risk factor for the
      development of self-injurious behaviors (Linehan, 1993, Cognitive-Behavioral
      Treatment of Borderline Personality Disorder, New York, Guilford Press). However,
      results from previous studies have been mixed, possibly indicating that this
      effect may not be the same for all individuals. In fact, some individuals may be
      more susceptible to environmental influences (i.e., phenotypic plasticity), and
      this susceptibility may be in part a function of genes that are involved in
      neuroplasticity (e.g., the brain-derived neurotrophic factor [BDNF] Val66Met
      polymorphism). METHOD: We explored the interaction between retrospective reports
      of childhood emotional environment and the BDNF Val66Met polymorphism in relation
      to a history of two main types of self-injurious behaviors, suicide attempt and
      nonsuicidal self-injury (NSSI), in a sample of individuals with a history of
      involvement in the criminal justice system. RESULTS: For individuals with two Val
      alleles, there was a significant direct relationship between emotional
      maltreatment and self-injurious behaviors. However, the relationship was not
      significant for Met carriers. LIMITATIONS: The data are cross-sectional, which
      means causal inferences cannot be drawn. CONCLUSIONS: The results indicate the
      possibility of a common etiological pathway for NSSI and suicide attempts.

PMID- 23541843
TI  - Posttranslational mechanisms modulating the expression of the cytochrome P450 1A1
      gene by methylmercury in HepG2 cells: a role of heme oxygenase-1.
AB  - Recently we demonstrated the ability of mercuric chloride (Hg(2+)) in human
      hepatoma HepG2 cells to significantly decrease the TCDD-mediated induction of
      Cytochrome P450 1A1 (CYP1A1) mRNA, protein, and catalytic activity levels. In
      this study we investigated the effect of methylmercury (MeHg) on CYP1A1 in HepG2
      cells. For this purpose, cells were co-exposed to MeHg and TCDD and the
      expression of CYP1A1 mRNA, protein, and catalytic activity levels were
      determined. Our results showed that MeHg did not alter the TCDD-mediated
      induction of CYP1A1 mRNA, or protein levels; however it was able to significantly
      decrease CYP1A1 catalytic activity levels in a concentration-dependent manner.
      Importantly, this inhibition was specific to CYP1A1and was not radiated to other
      aryl hydrocarbon receptor (AhR)-regulated genes, as MeHg induced NAD(P)H:quinone
      oxidoreductase 1 mRNA and protein levels. Mechanistically, the inhibitory effect
      of MeHg on the induction of CYP1A1 coincided with an increase in heme oxygenase-1
      (HO-1) mRNA levels. Furthermore, the inhibition of HO-1 activity, by tin
      mesoporphyrin, caused a complete restoration of MeHg-mediated inhibition of
      CYP1A1 activity, induced by TCDD. In addition, transfection of HepG2 cells with
      siRNA targeting the human HO-1 gene reversed the MeHg-mediated inhibition of TCDD
      induced CYP1A1. In conclusion, this study demonstrated that MeHg inhibited the
      TCDD-mediated induction of CYP1A1 through a posttranslational mechanism and
      confirms the role of HO-1 in a MeHg-mediated effect.

PMID- 23541844
TI  - Efficient mobilization of a resistance derivative of pSLT, the virulence plasmid
      specific of Salmonella enterica serovar Typhimurium, by an IncI1 plasmid.
AB  - pUO-StVR2 is a derivative of pSLT, the virulence plasmid specific of Salmonella
      enterica serovar Typhimurium, which confers multidrug resistance. This plasmid is
      widespread among closely related isolates of S. Typhimurium, and often coexists
      with other plasmids like pStR12. The latter belongs to incompatibility group
      IncI1, was assigned to ST48 by pMLST (plasmid multilocus sequence typing), and
      confers resistance to streptomycin/spectinomycin, chloramphenicol, trimethoprim
      and sulphonamides, with the responsible genes (aadA1/aadA2, cmlA1, dfrA12 and
      sul3) located on a sul3-class 1 integron. When using clinical isolates of S.
      Typhimurium containing one (pUO-StVR2) or both (pUO-StVR2 and pStR12) plasmids as
      donors and Escherichia coli K12 J53 resistant to rifampicin as recipient, the
      conjugation frequencies of pUO-StVR2 and pStR12 were 10-8 and 10-3-10-5
      transconjugants/donor, respectively, while the transfer frequency of pUO-StVR2
      increased 102 up to 105 times through mobilization by pStR12, depending on the
      donor strain and experimental conditions. Mobilization of pUO-StVR2, a plasmid
      which encodes virulence and resistance functions, by compatible plasmids which
      coexist in the same bacterium can facilitate the spread of these properties in S.
      Typhimurium, one of the most common serovars of S. enterica.

PMID- 23541845
TI  - The 2 micron plasmid of Saccharomyces cerevisiae: a miniaturized selfish genome
      with optimized functional competence.
AB  - The 2 micron plasmid of Saccharomyces cerevisiae is a relatively small multi-copy
      selfish DNA element that resides in the yeast nucleus at a copy number of 40-60
      per haploid cell. The plasmid is able to persist in host populations with almost
      chromosome-like stability with the help of a partitioning system and a copy
      number control system. The first part of this article describes the properties of
      the partitioning system comprising two plasmid coded proteins, Rep1 and Rep2, and
      a partitioning locus STB. Current evidence supports a model in which the Rep-STB
      system couples plasmid segregation to chromosome segregation by promoting the
      physical association of plasmid molecules with chromosomes. In the second part,
      the focus is on the Flp site-specific recombination system housed by the plasmid,
      which plays a critical role in maintaining steady state plasmid copy number. The
      Flp system corrects any decrease in plasmid population by promoting plasmid
      amplification via a recombination induced rolling circle replication mechanism.
      Appropriate plasmid amplification, without runaway increase in copy number, is
      ensured by positive and negative regulation of FLP gene expression by plasmid
      coded proteins and by the control of Flp level/activity through post
      translational modification of Flp by the cellular sumoylation system. The Flp
      system has been successfully utilized to understand mechanisms of site-specific
      recombination and to bring about directed genetic alterations for addressing
      fundamental problems in biology and for accomplishing bio-engineering objectives.
      A particularly interesting, and perhaps less well known and underappreciated,
      application of Flp in revealing unique DNA topologies required to confer
      functional competence to DNA-protein machines is discussed.

PMID- 23541846
TI  - Clinical relevance of antineutrophil cytoplasmic antibodies in Algerian
      scleroderma patients.

PMID- 23541847
TI  - Intratympanic aberrant and hypoplastic carotid artery.
AB  - Intratympanically aberrant internal carotid artery(ICA) is a rarely seen vascular
      abnormality. We present here the combination of aberration and prominent
      hypoplasia of the ICA in a case. Intratympanic aberrant ICA, which is rarely
      cited as a cause of tinnitus and hearing loss, should be known as a reason to be
      kept in mind as it may lead to life-threatening complications. Generally, it has
      been defined upon massive bleeding during myringotomy, ear surgery or biopsy
      procedure. In this article, the audiological and radiological studies confirmed
      with CT and MR angiography conducted on an aberrant and hypoplastic internal
      carotid artery that was identified under the manubrium mallei in a 28-year-old,
      young male patient who presented with complaints about hearing loss and fullness
      in the left ear were presented along with a literature review. 

PMID- 23541848
TI  - [Considerations on issuing death certificates].

PMID- 23541849
TI  - Influence of socio-demographic, labour and professional factors on nursing
      perception concerning practice environment in Primary Health Care.
AB  - AIM: To analyze the perception of nursing professionals of the Madrid Primary
      Health Care environment in which they practice, as well as its relationship with
      socio-demographic, work-related and professional factors. DESIGN: Cross
      sectional, analytical, observational study. PARTICIPANTS AND CONTEXT:
      Questionnaire sent to a total of 475 nurses in Primary Health Care in Madrid
      (former Health Care Areas 6 and 9), in 2010. MAIN MEASUREMENTS: Perception of the
      practice environment using the Practice Environment Scale of the Nursing Work
      Index (PES-NWI) questionnaire, as well as; age; sex; years of professional
      experience; professional category; Health Care Area; employment status and
      education level. RESULTS: There was a response rate of 69.7% (331). The raw score
      for the PES-NWI was: 81.04 [95%CI: 79.18-82.91]. The factor with the highest
      score was "Support from Managers" (2.9 [95%CI: 2.8-3]) and the lowest "Workforce
      adequacy" (2.3 [95%CI: 2.2-2.4]). In the regression model (dependent variable:
      raw score in PES-NWI), adjusted by age, sex, employment status, professional
      category (coefficient B=6.586), and years worked at the centre (coefficient
      B=2.139, for a time of 0-2 years; coefficient B=7.482, for 3-10 years;
      coefficient B=7.867, for over 20 years) remained at p<=0.05. CONCLUSIONS: The
      support provided by nurse managers is the most highly valued factor in this
      practice environment, while workforce adequacy is perceived as the lowest. Nurses
      in posts of responsibility and those possessing a higher degree of training
      perceive their practice environment more favourably. Knowledge of the factors in
      the practice environment is a key element for health care organizations to
      optimize provision of care and to improve health care results.

PMID- 23541850
TI  - [Home palliative care medical history: A proposal for the integral care of
      terminal patients].

PMID- 23541851
TI  - Follow-up to 'Cholecystectomy in the presence of a large patent foramen ovale:
      laparoscopic or open?'.

PMID- 23541852
TI  - Bilateral total knee arthroplasties: a call for practice guidelines.

PMID- 23541853
TI  - Nail gun injuries to the hand.

PMID- 23541854
TI  - A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous
      secretion of multiple cardiotherapeutic cytokines and improves cardiac function
      in a rapid-pacing-induced model of canine heart failure.
AB  - OBJECTIVES: Cardiac functional deterioration in dilated cardiomyopathy (DCM) is
      known to be reversed by intramyocardial up-regulation of multiple
      cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown
      to paracrinally activate interstitial cells to release a variety of protective
      factors. We here hypothesized that intramyocardial delivery of a slow-releasing
      form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate
      cardiotherapeutic factors, leading to regional and global functional recovery in
      DCM. METHODS AND RESULTS: ONO1301 elevated messenger RNA and protein level of
      hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived
      factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro.
      Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and
      glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant
      global functional recovery in a canine rapid pacing-induced DCM model, assessed
      by echocardiography and cardiac catheterization (n = 5 each). Importantly,
      speckle-tracking echocardiography unveiled significant regional functional
      recovery in the ONO1301-delivered territory, consistent to significantly
      increased vascular density, reduced interstitial collagen accumulation,
      attenuated myocyte hypertrophy, and reversed mitochondrial structure in the
      corresponding area. CONCLUSIONS: Intramyocardial delivery of ONO1301SR, which is
      a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple
      cardiotherapeutic factors in the injected territory, leading to region-specific
      reverse left ventricular remodeling and consequently a global functional recovery
      in a rapid-pacing-induced canine DCM model, warranting a further preclinical
      study to optimize this novel drug-delivery system to treat DCM.

PMID- 23541856
TI  - Nonvalvular right atrial papillary fibroelastoma.

PMID- 23541857
TI  - [Proximal median nerve compression. A series of 35 consecutive cases].
AB  - Median nerve entrapment at the elbow and the proximal forearm represents 7 to 10
      % of median nerve mononeuropathies. Literature distinguishes two distinct
      syndromes: the pronator syndrome and the anterior interosseous nerve syndrome. We
      report a retrospective series of 35 cases of proximal compression of the median
      nerve, including a previous study of 13 cases assessed in 2001. Thirty-four
      patients were operated on between 1994 and 2011. The series included 15 men and
      19 women with a mean age of 57 years. Subjective complaints were the main reason
      of consulting with or without a deficit. All but one benefited from a
      preoperative electrical study. Neurography showed abnormalities in 18 cases and
      myography in 30 cases. At least one site of compression was found at surgery.
      Thirty-one cases, including nine of the 13 cases previously evaluated in 2001,
      were assessed with a mean follow-up of 69 months. Twenty-height considered them
      improved and all but one were objectively improved by surgery. The nine cases
      evaluated in 2001 had better results in 2011. Through this series and an
      exhaustive literature review, we concluded that there are no preoperative
      criteria that can differentiate a pronator teres syndrome from an anterior
      interosseous nerve syndrome. If no improvement occurs, surgical treatment should
      be proposed, one must then assess all potential sites of nerve entrapment.
      Patients must be informed that improvement can take several years.

PMID- 23541855
TI  - Adjuvant vancomycin for antibiotic prophylaxis and risk of Clostridium difficile
      infection after coronary artery bypass graft surgery.
AB  - OBJECTIVE: The incidence of hospital-acquired Clostridium difficile infection
      (CDI) has increased rapidly over the past decade; patients undergoing major
      surgery, including coronary artery bypass grafting (CABG), are at particular
      risk. Intravenous vancomycin exposure has been identified as an independent risk
      factor for CDI, but this is controversial. It is not known whether vancomycin
      administered for surgical site infection prophylaxis increases the risk of CDI.
      METHODS: Using data from the Premier Perspective Comparative Database, we
      assembled a cohort of 69,807 patients undergoing CABG surgery between 2004 and
      2010 who received either a cephalosporin alone (65.1%) or a cephalosporin plus
      vancomycin (34.9%) on the day of surgery. Patients were observed for CDI until
      discharge from the index hospitalization. In these groups, we evaluated the
      comparative rate of postoperative CDI with Cox models; confounding was addressed
      using propensity scores. RESULTS: In all, 77 (0.32%) of the 24,393 patients
      receiving a cephalosporin plus vancomycin and 179 (0.39%) of the 45,414 patients
      receiving a cephalosporin alone had postoperative CDI (unadjusted hazard ratio
      [HR], 0.73; 95% confidence interval [CI], 0.56-0.95). After adjusting for
      confounding variables with either propensity score matching or stratification,
      there was no meaningful association between adjuvant vancomycin exposure and
      postoperative CDI (HR, 0.85; 95% CI, 0.61-1.19; and HR, 0.85; 95% CI, 0.63-1.15,
      respectively). Results of multiple sensitivity analyses were similar to the main
      findings. CONCLUSIONS: After adjustment for patient and surgical characteristics,
      a short course of prophylactic vancomycin was not associated with an increased
      risk of CDI among patients undergoing CABG surgery.

PMID- 23541858
TI  - Yield of repeat routine MEG recordings in clinical practice.
AB  - From 377 consecutive MEG studies for patients with intractable epilepsy performed
      at the Cleveland Clinic between 2008 and 2011, 19 patients were referred for a
      repeat MEG. Source localization was done using a single equivalent current dipole
      (ECD) model on identified interictal spike activity. Clinical, neuroimaging, and
      concurrent EEG and MEG findings were reviewed. The most common reasons for
      repeating MEG were as follows: negative initial study in 6 patients, paucity of
      recorded interictal discharges in 4, failed surgeries in 3, uncertain findings in
      the first study in 2, and research-related reasons in 4. Repeat MEG provided new
      localizing findings in 11/19 patients (58%), of whom 6 had negative or rare
      interictal findings in the first study. Lobar concordance of dipoles was present
      in 6 (85%) of the 7 patients with positive findings in both MEG studies. This
      study demonstrates that a repeat MEG may provide new localization data when a
      previous recording shows limited or no interictal abnormalities.

PMID- 23541859
TI  - Psychopathological and peripheral levels of neurobiological correlates of
      obsessive-compulsive symptoms in patients with epilepsy: a hospital-based study.
AB  - OBJECTIVES: Obsessive-compulsive symptoms (OCSs) and disorder (OCD) are often
      underdiagnosed in the out-patient epilepsy clinic. This work aimed at determining
      the risks and comorbidities (psychopathological and neurobiological correlates)
      of OCSs in treated adults with idiopathic epilepsy recruited from a university
      hospital. METHODS: Psychiatric evaluation was done using DSM-IV (The Diagnostic
      and Statistical Manual of Mental Health Disorders). Obsessive-compulsive disorder
      was identified using the Mini International Neuropsychiatric Interview (MINI).
      The Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A),
      and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were used to determine the
      severity of the related psychiatric symptoms. RESULTS: Out of 474 patients
      screened, included in this study were 107 with no psychiatric symptoms and 188
      with OCSs [classified as those with at least OCSs=93; mild OCSs=36; moderate,
      severe, and extreme OCSs=59]. A hundred healthy subjects were included as
      controls. Blood concentrations of serotonin, adrenaline, noradrenaline, and
      dopamine were measured. Compared with controls, patients with OCSs had higher
      frequencies of depression and anxiety. Low concentrations of serotonin,
      adrenaline, noradrenaline, and dopamine were reported regardless of the presence
      or the absence of psychiatric symptoms, OCS severities, and antiepileptic drug
      (AED)-related variables (dose and serum drug level). Significant correlations
      were identified between Y-BOCS, BDI-II, and HAM-A scores, age, age at onset, and
      concentrations of noradrenaline. CONCLUSION: This study indicates that a) OCSs
      are common in patients with epilepsy. Male sex, age, duration of illness, seizure
      focus, lateralization, and intractability to AEDs are its main risks; b)
      depression and anxiety are comorbid psychopathologies; and c) serotonin,
      catecholamines, and dopamine are linked to epilepsy-related variables and its
      comorbid psychopathies but not to its medications.

PMID- 23541860
TI  - Naming outcome prediction in patients with discordant Wada and fMRI language
      lateralization.
AB  - OBJECTIVE: Investigations of the validity of fMRI as an alternative to Wada
      language testing have yielded Wada/fMRI discordance rates of approximately 15%,
      but almost nothing is known regarding the relative accuracy of Wada and fMRI in
      discordant cases. The objective of this study was to determine which of the two
      (the Wada test or the language fMRI) is more predictive of postoperative naming
      outcome following left anterior temporal lobectomy in discordant cases. METHODS:
      Among 229 patients with epilepsy who prospectively underwent Wada and fMRI
      language testing, ten had discordant language lateralization results, underwent
      left anterior temporal lobectomy, and returned for postoperative language
      testing. The relative accuracy of Wada and fMRI for predicting language outcome
      was examined in these cases. RESULTS: Functional magnetic resonance imaging
      provided a more accurate prediction of language outcome in seven patients, Wada
      was more accurate in two patients, and the two tests were equally accurate in one
      patient. CONCLUSIONS: In cases of discordance, fMRI predicted postsurgical naming
      outcome with relatively better accuracy compared to the Wada test.

PMID- 23541861
TI  - Optimal design of an individual endoprosthesis for the reconstruction of
      extensive mandibular defects with finite element analysis.
AB  - AIM: The aim of this study was to evaluate the finite element analysis (FEA)
      approach to assess biomechanical performance of individual endoprostheses used in
      the reconstruction of extensive mandibular defects, and to explore an available
      strategy for the optimal design of prostheses. MATERIAL AND METHODS: A female
      patient experienced fracture of a titanium mandibular endoprosthesis one year
      after reconstructive surgery. The endoprosthesis was placed during resection of a
      mandibular carcinoma. Using CT data, a finite element analysis (FEA) of the
      implant was performed to identify potential causes for this mechanical failure.
      Based on the first FEA analysis, modifications of the prosthesis geometry and
      screw configuration were carried out. FEA was performed for each subsequent
      modification until no stress concentration areas were identified. The final
      version of the titanium prosthesis was implanted during the second mandibular
      reconstruction. RESULTS: The FEA model was constructed, based on the geometrical
      data of the patient. Two areas of stress concentration were identified in the
      original prosthesis: - at the top surface of the left stem, 1.5 cm away from the
      corner (the peak stress was 616 MPa) and - on the exterior surface of the right
      stem, close to the mandibular stump margin. The mechanical failure occurred at
      the top surface of the left stem. Some common characteristics of the
      biomechanical performance were noted in the two models, but lower overall stress
      was achieved in the second, optimized prosthesis. By thickening the recognized
      high stress areas, and attenuating those areas subject to less stress, then
      adopting a quadrilateral screw configuration, this dispersed the stress more
      evenly in the optimized endoprosthesis. Function in the optimized reconstructed
      mandible was observed for 3 years without significant endoprosthesis related
      complication. CONCLUSION: In some patients with extensive mandibular defects, the
      individually tailored endoprosthesis constructed with regard to minimizing stress
      concentration using this method seems to have a place. The prosthesis geometry
      and screw configuration influence the stress-strain distribution on the
      reconstructed mandible. Our FEA approach can optimize the design of individual
      endoprostheses and give the reconstructed mandible improved biomechanical
      performance.

PMID- 23541862
TI  - Collagen degradation by tumor-associated trypsins.
AB  - In normal soft tissues, collagen is degraded primarily by collagenases from the
      matrix metalloproteinase family. Yet, collagenase-like activity of tumor
      associated isoforms of other enzymes might be involved in cancer invasion as
      well. In the present study, we systematically examined collagen degradation by
      non-sulfated isoforms of trypsins, which were proposed to possess such an
      activity. We found that non-sulfated trypsin-1, -2, and -3 were able to cleave
      non-helical and unfolded regions of collagen chains but not the intact triple
      helix, similar to sulfated trypsins produced by the pancreas. Trypsin-2 sulfation
      did not affect the cleavage rate either. An apparent triple helix cleavage by
      tumor-associated trypsin-2 reported earlier likely occurred after triple helix
      unfolding during sample denaturation for gel electrophoresis. Nevertheless, tumor
      associated trypsins might be important for releasing collagen from fibers through
      telopeptide cleavage as well as for degrading unfolded collagen chains, e.g.
      after initial cleavage and destabilization of triple helices by collagenases.

PMID- 23541863
TI  - Repertoire of Theileria equi immunodominant antigens bound by equine antibody.
AB  - Theileriosis in horses and cattle is caused by tick-borne Apicomplexa parasites
      and results in death or life-long infection in their respective hosts.
      Transmission risk associated with persistent infection severely limits movement
      of horses and cattle resulting in economic losses. The recent reemergence of
      Theileria equi infection in U.S. horses demonstrates the continual threat
      Apicomplexa parasites represent to global animal health. A paucity of data
      concerning equine immune responses to T. equi, including antigens recognized by
      antibodies in clinically asymptomatic, persistently infected horses, precludes
      vaccine development. Therefore, this investigation was initiated to characterize
      antigens recognized by the equine antibody response to T. equi. This goal was
      accomplished by defining T. equi merozoite antigens that are recognized by
      antibodies in horses infected with distinct T. equi isolates. Previously it was
      shown that equine post-infection serum consistently recognized at least five T.
      equi merozoite antigens, but their precise identity remained unknown. To
      determine specificity of antibody target identification, T. equi merozoite
      antigens were first isolated using equine post-infection serum in affinity
      chromatography. Proteins recognized by the equine antibodies were then isolated
      from two-dimensional electrophoresis gels, and analyzed by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) using the recently available T. equi genome
      database. Five T. equi antigens were identified and include Equi Merozoite
      Antigen-2 (EMA-2), EMA-3 and EMA-6, a previously uncharacterized protein
      annotated as "signal peptide containing protein", and 40S ribosomal protein S12.

PMID- 23541864
TI  - Context-aware Augmented Reality in laparoscopic surgery.
AB  - Augmented Reality is a promising paradigm for intraoperative assistance. Yet,
      apart from technical issues, a major obstacle to its clinical application is the
      man-machine interaction. Visualization of unnecessary, obsolete or redundant
      information may cause confusion and distraction, reducing usefulness and
      acceptance of the assistance system. We propose a system capable of automatically
      filtering available information based on recognized phases in the operating room.
      Our system offers a specific selection of available visualizations which suit the
      surgeon's needs best. The system was implemented for use in laparoscopic liver
      and gallbladder surgery and evaluated in phantom experiments in conjunction with
      expert interviews.

PMID- 23541865
TI  - Displacement of the hip center of rotation after arthroplasty of Crowe III and IV
      dysplasia: a radiological and biomechanical study.
AB  - To study the direction and biomechanical consequences of hip center of rotation
      (HCOR) migration in Crowe type III and VI hips after total hip arthroplasty, post
      operative radiographs and CT scans of several unilaterally affected hips were
      evaluated. Using a three-dimensional model of the human hip, the HCOR was moved
      in all directions, and joint reaction force (JRF) and abductor muscle force (AMF)
      were calculated for single-leg stance configuration. Comparing to the normal
      side, HCOR had displaced medially and inferiorly by an average of 23.4% and
      20.8%, respectively, of the normal femoral head diameter. Significant decreases
      in JRF (13%) and AMF (46.13%) were observed in a presumptive case with that
      amount of displacement. Isolated inferior displacement had a small, increasing
      effect on these forces. In Crowe type III and IV hips, the HCOR migrates
      inferiorly and medially after THA, resulting in a decrease in JRF, AMF, and
      abductor muscle contraction force.

PMID- 23541866
TI  - Activity, sleep and cognition after fast-track hip or knee arthroplasty.
AB  - Optimized perioperative care after total hip and knee arthroplasty (THA/TKA) has
      decreased length of stay (LOS) but data on activity, sleep and cognition after
      discharge are limited. We included 20 patients >= 60 years undergoing THA/TKA,
      monitoring them for 3 days preoperatively and 9 days postoperatively with
      actigraphs for sleep and activity assessment. Pain scores were recorded daily.
      Cognition was evaluated by 2 cognitive tests. Results showed a mean age was 70.5
      years and mean LOS was 2.6 days. Actigraphs showed increased daytime sleep and
      decreased motor activity postoperatively. Early postoperatively cognitive decline
      and increased pain returned to preoperative levels by postoperative day (POD) 5
      9. Despite the small sample size the study illustrated that post-discharge
      activity is decreased and daytime sleep is increased after fast-track THA/TKA,
      while cognition and pain return to preoperative levels by POD 9. Objective
      assessment of these recovery parameters may be valuable in future interventional
      studies to enhance recovery after THA/TKA.

PMID- 23541867
TI  - Knee pain during the first three months after unilateral total knee arthroplasty:
      a multi-centre prospective cohort study.
AB  - Many patients have an unfavourable pain outcome post total knee arthroplasty
      (TKA). This multi-centre prospective cohort study recorded weekly pain scores one
      week before TKA and 12 weeks post TKA. 96 patients were enrolled into the study.
      Patients kept a record of their weekly scores pre-operation and post-operation by
      using the visual acuity score. Pain was divided into "best" pain score (lowest
      pain score) and "worst" pain score (highest pain score). Patients with a pre
      operative pain scores <= 4 were identified as an at risk group for poor pain
      outcome. Female gender, age and anaesthetics type were not identified as risk
      factors for poor pain outcome. Pain trajectory analysis also identified general
      patterns of pain response post TKA.

PMID- 23541868
TI  - The effect of tranexamic acid on blood loss and transfusion rate in primary total
      knee arthroplasty.
AB  - Allogeneic blood transfusions remain common in primary total knee arthroplasty.
      We reviewed our experience with 2269 consecutive primary total knee
      arthroplasties in 2069 patients over a 3.5 year period. In our cohort, 1838
      received no TXA, 330 received TXA via IV infusion, and 130 had TXA applied
      topically. The need for blood transfusion, as well as hematocrit levels
      immediately after surgery in the recovery room and the day of discharge were
      recorded. Tranexamic acid infusion demonstrated a statistically significant
      decrease in blood transfusion (P=0.001), as did topical application of TXA
      (P=0.019). The transfusion rate without TXA was 6.5% (120/1839) but only 0.3%
      (1/330) with TXA infusion. There were no transfusions (0/130) with topical TXA.
      Statistical differences were also noted in both immediate post operative and day
      of discharge hematocrit levels in patients having TXA infusion while those values
      for patients with TXA irrigation failed to obtain statistical significance. No
      significant change in the rate of symptomatic deep venous thrombosis or pulmonary
      embolism was noted.

PMID- 23541869
TI  - Rural vs. urban utilization of total joint arthroplasty.
AB  - The purpose of this study was to analyze the association between patient
      demographics and hospital demographics on utilization of total joint arthroplasty
      in rural and urban populations from the National Inpatient Sample database. Any
      patient that was discharged after a primary total hip or primary total knee
      arthroplasty was included in this study. Results showed that rural patients
      living in a Northeastern hospital region compared to West, less than 65 years of
      age, females, Blacks and Hispanics were less likely to undergo total joint
      arthroplasty compared to their urban counterparts. Rural patient were more likely
      to undergo total joint arthroplasty compared to their urban counterparts if they
      were in the Midwest and had Medicare as their primary payer provider.

PMID- 23541870
TI  - 14-year median follow-up using the press-fit condylar sigma design for total knee
      arthroplasty.
AB  - Median 14-year follow-up (mean 11.8 years) of a cemented primary posterior
      cruciate-retaining total knee arthroplasty (TKA) utilizing the Press-Fit Condylar
      (PFC) Sigma design was evaluated in 77 patients (79 TKA). Follow-up assessment
      included implant survivorship, x-rays, Knee Society rating system, and clinical
      evaluation. Radiographic analysis demonstrated minor non-progressive osteolysis
      in 40% (10/25) knees. Two revisions, one for instability at 4 years and one for
      polyethylene wear at 10 years were performed. Survivorship of the PFC Sigma knee
      implant was 97% using revision for any reason and 100% using aseptic loosening as
      endpoints. The PFC Sigma had excellent survivorship at 14 years, the longest
      clinical follow-up reported.

PMID- 23541871
TI  - Morphology and thermal properties of clay/PMMA nanocomposites obtained by
      miniemulsion polymerization.
AB  - Miniemulsion polymerization was used as the synthetic method to produce
      clay/poly(methyl methacrylate) nanocomposites. Two kinds of interfacial
      interactions clay-polymer particle were observed by electron microscopy, one
      where the polymer particles are adhered on the surface of the larger fragments of
      clay, and another where nanometric fragments of clay are encapsulated by polymer
      particles. Variations in the glass transition temperature (T(g)) and
      thermomechanical properties of the matrix, as function of clay content, were
      observed. In particular, at the highest clay loading (1.0 wt%) depression of T(g)
      and thermomechanical properties were observed. The increased clay-polymer matrix
      interfacial area appears to be the conditioning factor that determines such
      behavior.

PMID- 23541872
TI  - Entry inhibitors and their use in the treatment of HIV-1 infection.
AB  - Entry of HIV into target cells is a complex, multi-stage process involving
      sequential attachment and CD4 binding, coreceptor binding, and membrane fusion.
      HIV entry inhibitors are a complex group of drugs with multiple mechanisms of
      action depending on the stage of the viral entry process they target. Two entry
      inhibitors are currently approved for the treatment of HIV-infected patients.
      Maraviroc, a CCR5 antagonist, blocks interactions between the viral envelope
      proteins and the CCR5 coreceptor. Enfuvirtide, a fusion inhibitor, disrupts
      conformational changes in gp41 that drive membrane fusion. A wide array of
      additional agents are in various stages of development. This review covers the
      entry inhibitors and their use in the treatment of HIV-infected patients.

PMID- 23541873
TI  - Sudden unexpected neonatal death due to late onset group B streptococcal sepsis-
      a case report.
AB  - We report a case of sudden unexpected death due to late onset neonatal group B
      streptococcal sepsis. A male neonate weighing 2731g was born at 35week
      gestational age, and discharged at the age of 4days after the birth. At 6days
      after the discharge (10days after the birth), because of consciousness loss and
      hypothermia, the neonate was conveyed to an emergency hospital, eventually
      followed by his death. Forensic autopsy revealed neither severe trauma nor
      cardiac anomaly. Both lungs were edematous. Histopathologically, a lot of
      bacterial clusters were found in the lungs and intracerebral vessels.
      Cerebrospinal fluid contained a lot of leukocytes. Streptococcus agalactiae was
      detected in the specimens from the feces and the blood. Collectively, we
      diagnosed that the cause of the neonate's death was late onset group B
      streptococcal sepsis. In autopsy cases of neonates, careful macroscopic and
      microscopic observations and bacteriological/virological examination should be
      performed. 

PMID- 23541874
TI  - Three dimensional surface analyses of pubic symphyseal faces of contemporary
      Japanese reconstructed with 3D digitized scanner.
AB  - Three dimensional pubic bone images were analyzed to quantify some age-dependent
      morphological changes of the symphyseal faces of contemporary Japanese residents.
      The images were synthesized from 145 bone specimens with 3D measuring device.
      Phases of Suchey-Brooks system were determined on the 3D pubic symphyseal images
      without discrepancy from those carried out on the real bones because of the high
      fidelity. Subsequently, mean curvatures of the pubic symphyseal faces to examine
      concavo-convex condition of the surfaces were analyzed on the 3D images. Average
      values of absolute mean curvatures of phase 1 and 2 groups were higher than those
      of phase 3-6 ones, whereas the values were approximately constant over phase 3
      presumably reflecting the inactivation of pubic faces over phase 3. Ratio of the
      concave areas increased gradually with progressing phase or age classes, although
      convex areas were predominant in every phase. 

PMID- 23541875
TI  - Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong
      independent predictor of radiographic progression over 5 years follow-up.
AB  - OBJECTIVES: Age-related changes in articular cartilage are likely to play a role
      in the etiology of osteoarthritis (OA). One of the major age-related changes in
      cartilage is the accumulation of advanced glycation end products (AGEs). The
      present study evaluates whether pentosidine can predict radiographic progression
      and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA.
      DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee
      (CHECK) were used. Radiographic progression and burden were assessed by X-rays of
      both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline
      pentosidine levels (and urinary CTXII as a comparator) were measured by high
      performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay
      (ELISA). Univariable and multivariable associations including baseline
      radiographic damage, age, gender, body mass index (BMI) and kidney function were
      performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type
      II collagen (uCTXII) correlated with radiographic progression and burden. In
      general pentosidine did not have an added predictive value to uCTXII for
      progression nor burden of the disease. The best prediction was obtained for
      burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly
      determined by baseline radiographic damage (without this parameter R(2) = 0.07
      0.17). Interestingly, pentosidine significantly added to prediction of osteophyte
      formation, whereas uCTXII significantly added to prediction of JSN in
      multivariable analysis. CONCLUSION: Pentosidine adds to prediction of
      radiographic progression and burden of osteophyte formation and uCTXII to
      radiographic progression and burden of JSN, but overall skin pentosidine did not
      perform better that uCTXII in predicting radiographic progression or burden.
      Burden of damage over 5 years is mainly determined by radiographic joint damage
      at baseline.

PMID- 23541876
TI  - Quantification of protonation in organic solvents using solution NMR
      spectroscopy: implication in salt formation.
AB  - PURPOSE: Investigate the use of solution NMR spectroscopy to evaluate whether the
      general DeltapKa rule is valid in organic solvents. Such information may be
      useful in evaluation of acid-base reactions and solvent selection for salt
      formation. METHODS: (1)H NMR chemical shift changes in model bases during
      titration with acids, and separately, on the addition of acids at a molar ratio
      of 1:1 were determined in water, dimethyl sulfoxide, and methanol. The effect of
      acid strength on the fraction of ionized base was examined. RESULTS: (1)H NMR
      chemical shift changes indicated protonation (in situ salt formation). Different
      media affected the observed chemical shift changes. In all media investigated the
      data followed the DeltapKa (base-acid) general rule, that the pKa value of the
      acids should be 2-3 units lower than the pKa of the base to ensure proton
      transfer. The addition of water into organic solvents increased the fraction of
      ionized base. CONCLUSIONS: Protonation, as measured by chemical shift changes
      using solution NMR spectroscopy, provided novel insight on potential salt
      formation in different media. Even though pKa values change with the solvent, the
      general DeltapKa rule can be applied in different solvent systems. Solution NMR
      spectroscopy appears to be a useful tool to evaluate salt formation reaction and
      process control in different solvent systems.

PMID- 23541877
TI  - Increased blood serotonin concentrations are correlated with reduced
      tension/anxiety in healthy postpartum lactating women.
AB  - The serotonin (5-HT) system in the brain plays an important role in mood
      regulation. The postpartum period is considered a high-risk time for mood and
      anxiety disorders. We assessed changes in 5-HT levels in whole blood (as an
      indicator of brain 5-HT concentrations) and mood states before and after delivery
      in 28 healthy, lactating postpartum women. Mood states were evaluated using
      Profile of Mood States questionnaires (POMS). Measurements were done on the same
      day in early (first week) and late (third-fourth and sixth-seventh weeks)
      postpartum, and compared with those in the third trimester and in age-matched,
      healthy, non-pregnant women. Mean 5-HT concentrations were significantly higher
      and mean tension/anxiety scores of POMS were significantly lower in late (but not
      early) postpartum than in the third trimester or non-pregnant controls. 5-HT
      concentrations correlated with tension/anxiety in the third trimester and late
      postpartum, indicating an important role for the 5-HT system in the regulation of
      tension/anxiety in healthy postpartum women. The mechanism underlying the changes
      in the 5-HT system may be rapid inhibition induced by the marked decrease in
      estradiol after delivery and gradual excitation caused by lactation-induced brain
      oxytocin release during the postpartum period. 

PMID- 23541878
TI  - Alzheimer's disease: connecting findings from graph theoretical studies of brain
      networks.
AB  - The interrelationships between pathological processes and emerging clinical
      phenotypes in Alzheimer's disease (AD) are important yet complicated to study,
      because the brain is a complex network where local disruptions can have
      widespread effects. Recently, properties in brain networks obtained with
      neuroimaging techniques have been studied in AD with tools from graph theory.
      However, the interpretation of graph alterations remains unclear, because the
      definition of connectivity depends on the imaging modality used. Here we examined
      which graph properties have been consistently reported to be disturbed in AD
      studies, using a heuristically defined "graph space" to investigate which
      theoretical models can best explain graph alterations in AD. Findings from
      structural and functional graphs point to a loss of highly connected areas in AD.
      However, studies showed considerable variability in reported group differences of
      most graph properties. This suggests that brain graphs might not be isometric,
      which complicates the interpretation of graph measurements. We highlight
      confounding factors such as differences in graph construction methods and provide
      recommendations for future research.

PMID- 23541879
TI  - [The Spanish AIDS Study Group and Spanish National AIDS Plan (GESIDA/Secretaria
      del Plan Nacional sobre el Sida) recommendations for the treatment of
      tuberculosis in HIV-infected individuals (Updated January 2013)].
AB  - This consensus document was prepared by an expert panel of the Grupo de Estudio
      de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida
      (PNS [Spanish National AIDS Plan]). The document updates current guidelines on
      the treatment of tuberculosis (TB) in HIV-infected individuals contained in the
      guidelines on the treatment of opportunistic infections published by GESIDA and
      PNS in 2008. The document aims to facilitate the management and treatment of HIV
      infected patients with TB in Spain, and includes specific sections and
      recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB,
      and extensively drug-resistant TB, in this population. The consensus guidelines
      also make recommendations on the treatment of HIV-infected patients with TB in
      special situations, such as chronic liver disease, pregnancy, kidney failure, and
      transplantation. Recommendations are made on the timing and initial regimens of
      antiretroviral therapy in patients with TB, and on immune reconstitution syndrome
      in HIV-infected patients with TB who are receiving antiretroviral therapy. The
      document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or
      treatment of TB in children. The quality of the evidence was evaluated and the
      recommendations graded using the approach of the Grading of Recommendations
      Assessment, Development and Evaluation Working Group. 

PMID- 23541880
TI  - Biological, biochemical and histopathological features related to parasitic
      castration of Biomphalaria glabrata infected by Schistosoma mansoni.
AB  - Parasitic castration in the snail-trematode relationship can be understood as any
      change in the reproductive function of the snail that is due to interference by
      the developing larvae inside the snail that leads to the reduction or complete
      disruption of egg-laying activity. This study was designed to observe the
      parasitic castration of Biomphalaria glabrata infected with Schistosoma mansoni
      during both the pre-patent and patent periods. The effect of infection on snail
      fecundity and fertility, growth rate and survival was studied during the 62 days
      following miracidia exposure. An integrated approach was employed that used
      biochemical and histological tools over the same period. To study the effect of
      infection on reproduction, we individually exposed 30 snails to 5 miracidia each
      and tracked their fertility and fecundity. For our histopathological studies, 50
      snails were exposed to 20 miracidia each, and for our histochemical studies, 50
      snails were exposed to 5 miracidia each. An equal number of uninfected snails
      were used as a control for each group. The B. glabrata exposed to the BH strain
      of S. mansoni showed 50% positivity for cercarial shedding. Both the experimental
      and control groups showed 100% survival. The pre-patent period lasted until 39
      days after exposure to miracidia. Exposed snails that showed cercarial shedding
      exhibited higher growth rates than either exposed snails that did not demonstrate
      cercarial shedding or uninfected controls. Exposed snails without cercarial
      shedding and uninfected controls showed no differences in the reproductive
      parameters evaluated during the patent period; snails experiencing cercarial
      shedding showed a reduction in fecundity and fertility. These snails began to lay
      eggs only after the 50th day post miracidia exposure. The haemolymph glucose
      levels showed an oscillating pattern that decreased during periods of greater
      mobilisation of energy by the larvae and was accompanied by a depletion of
      glycogen in the cephalopodal mass and digestive gland. Histopathological
      examination at 55 days showed that the ovotestis was highly atrophied. There was
      almost complete disappearance of germ cells, and the supporting stroma formed a
      nearly empty net. At day 45, the infected digestive gland showed a high
      cylindrical epithelium with little preserved cytoplasm. The contents of the
      secretory granules of the albumen gland of infected animals stained with Alcian
      blue (AB), pH 1.0, indicating the presence of sulphated carbohydrates. Thus,
      parasitic castration in the B. glabrata-S. mansoni model may be regulated
      directly and indirectly by the developmental stage of the trematode and the
      biochemical and histopathological alterations during the patent period of
      infection.

PMID- 23541881
TI  - TgMAPK1 is a Toxoplasma gondii MAP kinase that hijacks host MKK3 signals to
      regulate virulence and interferon-gamma-mediated nitric oxide production.
AB  - The parasite Toxoplasma gondii controls tissue-specific nitric oxide (NO),
      thereby augmenting virulence and immunopathology through poorly-understood
      mechanisms. We now identify TgMAPK1, a Toxoplasma mitogen-activated protein
      kinase (MAPK), as a virulence factor regulating tissue-specific parasite burden
      by manipulating host interferon (IFN)-gamma-mediated inducible nitric oxide
      synthase (iNOS). Toxoplasma with reduced TgMAPK1 expression (TgMAPK1(lo))
      demonstrated that TgMAPK1 facilitates IFN-gamma-driven p38 MAPK activation,
      reducing IFN-gamma-generated NO in an MKK3-dependent manner, blunting IFN-gamma
      mediated parasite control. TgMAPK1(lo) infection in wild type mice produced >=ten
      fold lower parasite burden versus control parasites with normal TgMAPK1
      expression (TgMAPK1(con)). Reduced parasite burdens persisted in IFN-gamma KO
      mice, but equalized in normally iNOS-replete organs from iNOS KO mice. Parasite
      MAPKs are far less studied than other parasite kinases, but deserve additional
      attention as targets for immunotherapy and drug discovery.

PMID- 23541882
TI  - In vitro activity of pineapple extracts (Ananas comosus, Bromeliaceae) on
      Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).
AB  - Measures to control the cattle tick, Rhipicephalus (Boophilus) microplus, based
      only on chemical products are becoming unsustainable, mainly because of the
      development of resistance. The objective of this study was to test the effect of
      the aqueous extract of pineapple skin (AEPS) and bromelain extracted from the
      stem (Sigma-Aldrich(r), B4882) on engorged females and larvae of R. (B.)
      microplus in vitro. These substances were diluted in water and evaluated at eight
      concentrations. Engorged females were collected and distributed in groups of 10,
      with three repetitions for each treatment. After immersion in the solutions, the
      females were placed in an incubator for observation of survival, oviposition and
      larval hatching. The larval packet method was used, also with three repetitions
      with about 100 larvae each. The packets were incubated and the readings were
      performed after 24 h. The estimated reproduction and efficacy of the solutions
      were calculated. The LC(50) and LC(90) were estimated using the Probit procedure
      of the SAS program. The eight concentrations were compared within each treatment
      by the Tukey test. For the experiment with engorged females, the most effective
      concentrations were 125, 250 and 500 mg/mL: 33%, 48% and 59% for the AEPS and
      27%, 51% and 55% for the bromelain. The LC(50) and LC(90) values were,
      respectively, 276 and 8691 mg/mL for AEPS and 373 and 5172 mg/mL for bromelain.
      None of the dilutions tested was effective against the larvae of R. (B.)
      microplus. This is the first report of the action of pineapple extracts or their
      constituents on cattle ticks. The results demonstrate that further studies
      regarding composition of tick cuticle, with evaluation of other solvents and
      formulations, should be conducted seeking to enhance the effect of pineapple
      extracts and compounds against this ectoparasite.

PMID- 23541883
TI  - Effect of IL-22 on DNA vaccine encoding LACK gene of Leishmania major in BALB/c
      mice.
AB  - In the present study, the effect of IL-22 together with the plasmid encoding LACK
      (Leishmania homolog of receptors for activated C-kinase) gene of Leishmania major
      on the trend of leishmaniasis in BALB/c mice was evaluated. Evaluation of the
      cellular and humoral immunity was performed by measurement of IL-4 and IFN-gamma,
      culture of splenocytes and MTT assay, and measurement of total IgG, IgG1, and
      IgG2a in the control and immunized groups. Clinical evaluations were also carried
      out by measurement of the lesion size, survival rate, and body weight of mice.
      Comparison of the mean size of lesions in the LACK and LACK+IL-22 groups
      demonstrated that the mean size of lesions of the two groups was significantly
      different from week four (p<0.05). The survival rate at day 170 after challenge
      for the PBS, pcDNA3 (empty plasmid), pcLACK (pcDNA3 containing LACK gene), and
      pcLACK+IL-22 groups were 20%, 40%, 60%, and 80%, respectively. According to the
      results of IFN-gamma, IL-4, total IgG, IgG1, and IgG2a measurement and the MTT
      assay, IL-22 obviously caused an increase in IFN-gamma production and a decrease
      in IL-4 production before and after the challenge (p<0.05). The results showed
      the effectiveness of IL-22 in DNA vaccine. It showed that IL-22 brought about Th1
      cytokine responses and high survival rate of mice.

PMID- 23541885
TI  - Outside and inside angiotensin.

PMID- 23541886
TI  - Analysis of sagittal spinopelvic parameters in cerebral palsy.
AB  - BACKGROUND CONTEXT: Knowledge of sagittal spinopelvic parameters is important for
      the treatment of cerebral palsy (CP) because they differ in the normal population
      and can induce symptoms. PURPOSE: To analyze the sagittal spinal alignment and
      the pelvic orientation in CP. STUDY DESIGN: Radiological analysis of patients
      with CP. METHODS: The study and control groups comprised 57 CP patients and 24
      healthy volunteers, respectively. All the patients underwent lateral radiography
      of the whole spine including hip joints. The radiographic parameters examined
      were sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), S1 overhang
      (OH), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL1
      and 2), and sagittal balance (SB). Statistical analysis was performed to identify
      the significant differences between the two study groups. In addition,
      correlations were sought between the parameters and symptoms. RESULTS: The PT and
      OH were significantly smaller in the CP patients, whereas SS, TLK, LL1, LL2, and
      SB were significantly greater (p<.05). Correlation analysis revealed significant
      relationships between the sagittal parameters. Specifically, PI was found to be
      associated with SS, PT, and OH, whereas the spinal parameters LL1 and LL2 were
      found to be related to TK and SB. Between spine and pelvic parameters, LL1 and
      LL2 were found to be related to SS, PT, PI, and OH and in addition, SB was found
      to be related to TLK, LL1, and LL2. An analysis of relations between the symptoms
      and parameters revealed a positive correlation between the severities of symptoms
      and PT, OH, and TLK (r=0.300, p=.023; r=0.306, p=.020; r=0.289, p=.029,
      respectively). CONCLUSIONS: A significant difference was observed in the sagittal
      spinopelvic parameters in the CP and normal control groups and was possibly
      related to the symptoms. The study shows that the evaluations of sagittal
      spinopelvic parameters could be useful during the treatment of disorders
      associated with CP.

PMID- 23541884
TI  - Expression of membrane anchored cytokines and B7-1 alters tumor microenvironment
      and induces protective antitumor immunity in a murine breast cancer model.
AB  - Many studies have shown that the systemic administration of cytokines or
      vaccination with cytokine-secreting tumors augments an antitumor immune response
      that can result in eradication of tumors. However, these approaches are hampered
      by the risk of systemic toxicity induced by soluble cytokines. In this study, we
      have evaluated the efficacy of 4TO7, a highly tumorigenic murine mammary tumor
      cell line, expressing glycosyl phosphatidylinositol (GPI)-anchored form of
      cytokine molecules alone or in combination with the costimulatory molecule B7-1
      as a model for potential cell or membrane-based breast cancer vaccines. We
      observed that the GPI-anchored cytokines expressed on the surface of tumor cells
      greatly reduced the overall tumorigenicity of the 4TO7 tumor cells following
      direct live cell challenge as evidenced by transient tumor growth and complete
      regression within 30 days post challenge. Tumors co-expressing B7-1 and GPI-IL-12
      grew the least and for the shortest duration, suggesting that this combination of
      immunostimulatory molecules is most potent. Protective immune responses were also
      observed following secondary tumor challenge. Further, the 4TO7-B7-1/GPI-IL-2 and
      4TO7-B7-1/GPI-IL-12 transfectants were capable of inducing regression of a wild
      type tumor growing at a distant site in a concomitant tumor challenge model,
      suggesting the tumor immunity elicited by the transfectants can act systemically
      and inhibit the tumor growth at a distant site. Additionally, when used as
      irradiated whole cell vaccines, 4TO7-B7-1/GPI-IL-12 led to a significant
      inhibition in tumor growth of day 7 established tumors. Lastly, we observed a
      significant decrease in the prevalence of myeloid-derived suppressor cells and
      regulatory T-cells in the tumor microenvironment on day 7 post challenge with
      4TO7-B7-1/GPI-IL-12 cells, which provides mechanistic insight into antitumor
      efficacy of the tumor-cell membrane expressed IL-12. These studies have
      implications in designing membrane-based therapeutic vaccines with GPI-anchored
      cytokines for breast cancer.

PMID- 23541887
TI  - The Subaxial Cervical Spine Injury Classification System: an external agreement
      validation study.
AB  - BACKGROUND CONTEXT: In 2007, the Subaxial Cervical Spine Injury Classification
      (SLIC) system was introduced demonstrating moderate reliability in an internal
      validation study. PURPOSE: To assess the agreement on the SLIC system using
      clinical data from a spinal trauma population and whether the SLIC treatment
      algorithm outcome improved agreement on treatment decisions among surgeons. STUDY
      DESIGN: An external classification validation study. PATIENT SAMPLE: Twelve
      spinal surgeons (five consultants and seven fellows) assessed 51 randomly
      selected cases. OUTCOME MEASURES: Raw agreement, Fleiss kappa, and intraclass
      correlation coefficient statistics were used for reliability analysis. Majority
      rules and latent class modeling were used for accuracy analysis. METHODS: Fifty
      one randomly selected cases with significant injuries of the cervical spine from
      a prospective consecutive series of trauma patients were assessed using the SLIC
      system. Neurologic details, plain radiographs, and computed tomography scans were
      available for all cases as well as magnetic resonance imaging in 21 cases (41%).
      No funds were received in support of this study. The authors have no conflict of
      interest in the subject of this article. RESULTS: The inter-rater agreement on
      the most severely affected level of injury was strong (kappa=0.76). The agreement
      on the morphologic injury characteristics was poor (kappa=0.29) and agreement on
      the integrity of the discoligamentous complex was average (kappa=0.46). The inter
      rater agreement on the treatment verdict after the total SLIC injury severity
      score was slightly lower than the surgeons' agreement on personal treatment
      preference (kappa=0.55 vs. kappa=0.63). Latent class analysis was not converging
      and did not present accurate estimations of the true classification categories.
      Based on these findings, no second survey for testing intrarater agreement was
      performed. CONCLUSIONS: We found poor agreement on the morphologic injury
      characteristics of the SLIC system, and its treatment algorithm showed no
      improved agreement on treatment decisions among surgeons. The authors discuss
      that the reproducibility of the SLIC system is likely to improve when unambiguous
      true morphologic injury characteristics are being implemented.

PMID- 23541888
TI  - Acute brainstem compression by intratumoral hemorrhages in an intracranial
      hypoglossal schwannoma.
AB  - A 77-year-old female in the hospital was found tachycardic and hypothermic by a
      nurse, and the patient's respiration subsequently ceased. Forensic autopsy
      revealed an intracranial cystic tumor that would have compressed the brainstem.
      On microscopic examination, the tumor was diagnosed as an Antoni A schwannoma
      growth, and recent multiple intratumoral hemorrhages in the intracranial
      schwannoma were observed, suggesting the sudden enlargement of the intracranial
      schwannoma due to intratumoral hemorrhaging. Accordingly, we diagnosed the cause
      of death as brainstem compression induced by the intratumoral hemorrhaging in the
      intracranial schwannoma. Meanwhile, a rhinopharyngeal tumor was also detected by
      the autopsy, which was compatible with an antemortem diagnosis of a dumbbell
      shaped hypoglossal schwannoma. 

PMID- 23541889
TI  - Five functional adipokinetic peptides expressed in the corpus cardiacum of the
      moth genus Hippotion (Lepidoptera, Sphingidae).
AB  - This is the first study that finds five adipokinetic hormones (AKHs) in the
      corpus cardiacum of an insect. From two species of the sphingid moth genus
      Hippotion, eson and celerio, three novel and two known AKHs were isolated and
      sequenced by deduction from multiple MS(n) electrospray mass data: two
      octapeptides are pGlu-Leu-Thr-Phe-Thr-Ser-Ser-Trp amide (denoted Hipes-AKH-I) and
      its Thr(7) analogue (Hipes-AKH-II); two nonapeptides are pGlu-Leu-Thr-Phe-Thr-Ser
      Ser-Trp-Gly amide (Manse-AKH) and its Thr(7) analogue (Hipes-AKH-III), as well as
      a decapeptide pGlu-Leu-Thr-Phe-Ser-Ser-Gly-Trp-Gly-Gln amide (Manse-AKH-II). All
      sequences were confirmed by identical behaviour of natural and synthetic peptides
      in reversed-phase HPLC and liquid chromatography coupled to electrospray mass
      spectrometry, resulting in identical retention times and tandem mass spectral
      data. High resolution mass spectrometry and retention time data also confirmed
      that the amino acid at position 10 in Manse-AKH-II is Gln and not the isobaric
      Lys. Conspecific injections of all five peptides in synthetic form and low doses
      caused hyperlipaemia in H. eson. Our results and pertaining literature suggest
      that five genes code for the mature peptides, which are very likely released
      during flight to provide energy for long distance migration in this genus via
      lipid oxidation; as all five peptides are active at low doses in a conspecific
      bioassay, it may be speculated, but not proven, that there is only one AKH
      receptor present in Hippotion that can bind all five peptides with high affinity.

PMID- 23541890
TI  - Characterization of signaling pathways coupled to melatonin receptors in
      gastrointestinal smooth muscle.
AB  - Melatonin, a close derivative of serotonin, is involved in physiological
      regulation of circadian rhythms. In the gastrointestinal (GI) system, melatonin
      exhibits endocrine, paracrine and autocrine actions and is implicated in the
      regulation of GI motility. However, it is not known whether melatonin can also
      act directly on GI smooth muscle cells. The aim of the present study was to
      determine the expression of melatonin receptors in smooth muscle and identify
      their signaling pathways. MT1, but not MT2 receptors are expressed in freshly
      dispersed and cultured gastric smooth muscle cells. Melatonin selectively
      activated Gq and stimulated phosphoinositide (PI) hydrolysis in freshly dispersed
      and cultured muscle cells. PI hydrolysis was blocked by the expression of Gq, but
      not Gi minigene in cultured muscle cells. Melatonin also caused rapid increase in
      cytosolic Ca(2+) as determined by epifluorescence microscopy in fura-2 loaded
      single smooth muscle cells, and induced rapid contraction. Melatonin-induced PI
      hydrolysis and contraction were blocked by a non-selective MT1/MT2 antagonist
      luzindole (1 MUM), but not by a selective MT2 antagonist 4P-PDOT (100 nM), and by
      the PLC inhibitor U73122. MT2 selective agonist IIK7 (100 nM) had no effect on PI
      hydrolysis and contraction. We conclude that rabbit gastric smooth muscle cells
      express melatonin MT1 receptors coupled to Gq. Activation of these receptors
      causes stimulation of PI hydrolysis and increase in cytosolic Ca(2+), and elicits
      muscle contraction.

PMID- 23541891
TI  - Designing interfaces of hydrogenase-nanomaterial hybrids for efficient solar
      conversion.
AB  - The direct conversion of sunlight into biofuels is an intriguing alternative to a
      continued reliance on fossil fuels. Natural photosynthesis has long been
      investigated both as a potential solution, and as a model for utilizing solar
      energy to drive a water-to-fuel cycle. The molecules and organizational structure
      provide a template to inspire the design of efficient molecular systems for
      photocatalysis. A clear design strategy is the coordination of molecular
      interactions that match kinetic rates and energetic levels to control the
      direction and flow of energy from light harvesting to catalysis. Energy
      transduction and electron-transfer reactions occur through interfaces formed
      between complexes of donor-acceptor molecules. Although the structures of several
      of the key biological complexes have been solved, detailed descriptions of many
      electron-transfer complexes are lacking, which presents a challenge to designing
      and engineering biomolecular systems for solar conversion. Alternatively, it is
      possible to couple the catalytic power of biological enzymes to light harvesting
      by semiconductor nanomaterials. In these molecules, surface chemistry and
      structure can be designed using ligands. The passivation effect of the ligand can
      also dramatically affect the photophysical properties of the semiconductor, and
      energetics of external charge-transfer. The length, degree of bond saturation
      (aromaticity), and solvent exposed functional groups of ligands can be
      manipulated to further tune the interface to control molecular assembly, and
      complex stability in photocatalytic hybrids. The results of this research show
      how ligand selection is critical to designing molecular interfaces that promote
      efficient self-assembly, charge-transfer and photocatalysis. This article is part
      of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems. 

PMID- 23541892
TI  - Deletion of beta-strands 9 and 10 converts VDAC1 voltage-dependence in an
      asymmetrical process.
AB  - Voltage-dependent anion selective channel isoform1 maintains the permeability of
      the outer mitochondrial membrane. Its voltage-gating properties are relevant in
      bioenergetic metabolism and apoptosis. The N-terminal domain is suspected to be
      involved in voltage-gating, due to its peculiar localization. However this issue
      is still controversial. In this work we exchanged or deleted the beta-strands
      that take contact with the N-terminal domain. The exchange of the whole hVDAC1
      beta-barrel with the homologous hVDAC3 beta-barrel produces a chimeric protein
      that, in reconstituted systems, loses completely voltage-dependence. hVDAC3 beta
      barrel has most residues in common with hVDAC1, including V143 and L150
      considered anchor points for the N-terminus. hVDAC1 mutants completely lacking
      either the beta-strand 9 or both beta-strands 9 and 10 were expressed, refolded
      and reconstituted in artificial bilayers. The mutants formed smaller pores.
      Molecular dynamics simulations of the mutant structure supported its ability to
      form smaller pores. The mutant lacking both beta-strands 9 and 10 showed a new
      voltage-dependence feature resulting in a fully asymmetric behavior. These data
      indicate that a network of beta-strands in the pore-walls, and not single
      residues, are required for voltage-gating in addition to the N-terminus.

PMID- 23541893
TI  - Molecular basis of SMC ATPase activation: role of internal structural changes of
      the regulatory subcomplex ScpAB.
AB  - In many bacteria, a homodimer of structural-maintenance-of-chromosomes proteins
      associates with two regulatory subunits (known as ScpA and ScpB), assembling a
      protein complex that plays a crucial role in chromosome organization and
      segregation. It remains poorly understood, however, how this complex might work
      at the mechanistic level. Here, we report crystal structures of the ScpAB core
      complex that display a highly unusual structure in which the central segment of
      ScpA winds around an asymmetrically oriented ScpB dimer. The two C-terminal
      domains of the ScpB dimer primarily interact with different regions of ScpA with
      different affinities. Moreover, flexible interdomain regions of ScpB contribute
      to a dynamic folding process of the ScpAB subcomplex. Together with other genetic
      and biochemical assays, we provide evidence that internal structural changes of
      the ScpAB subcomplex are tightly coupled with activation of the structural
      maintenance-of-chromosomes ATPase.

PMID- 23541894
TI  - Cryo-EM structure of a molluscan hemocyanin suggests its allosteric mechanism.
AB  - Hemocyanins are responsible for transporting O2 in the arthropod and molluscan
      hemolymph. Haliotis diversicolor molluscan hemocyanin isoform 1 (HdH1) is an 8
      MDa oligomer. Each subunit is made up of eight functional units (FUs). Each FU
      contains two Cu ions, which can reversibly bind an oxygen molecule. Here, we
      report a 4.5 A degrees  cryo-EM structure of HdH1. The structure clearly shows
      ten asymmetric units arranged with D5 symmetry. Each asymmetric unit contains two
      structurally distinct but chemically identical subunits. The map is sufficiently
      resolved to trace the entire subunit Ca backbone and to visualize densities
      corresponding to some large side chains, Cu ion pairs, and interaction networks
      of adjacent subunits. A FU topology path intertwining between the two subunits of
      the asymmetric unit is unambiguously determined. Our observations suggest a
      structural mechanism for the stability of the entire hemocyanin didecamer and 20
      ''communication clusters'' across asymmetric units responsible for its allosteric
      property upon oxygen binding.

PMID- 23541895
TI  - Adaptation of aminoacyl-tRNA synthetase catalytic core to carrier protein
      aminoacylation.
AB  - Amino acid:[carrier protein] ligases (aa:CP ligases) are recently discovered
      enzymes that are highly similar to class II aminoacyl-tRNA synthetases (aaRSs).
      However, while aaRSs aminoacylate tRNA and supply building blocks for ribosomal
      translation, aa:CP ligases transfer activated amino acids to the
      phosphopantetheine group of small carrier proteins. We have solved the crystal
      structure of an aa:CP ligase complexed with the carrier protein (CP). The CP
      prosthetic group enters the active site from a different direction than tRNA in
      class II aaRS complexes through an idiosyncratic tunnel. CP binds to aa:CP ligase
      in a fundamentally different manner compared to tRNA binding by structurally
      closely related aaRSs. Based on crystallographic analysis, an enzyme of altered
      CP specificity was designed, and the mechanism of amino acid transfer to the
      prosthetic group was proposed. The presented study reveals how a conserved class
      II aaRS catalytic core can adapt to another function through minor structural
      alterations.

PMID- 23541896
TI  - Structural mechanism of CCM3 heterodimerization with GCKIII kinases.
AB  - Mutation of CCM3 causes cerebral cavernous malformations of the vasculature,
      leading to focal neurological deficits, seizures, and hemorrhagic stroke. CCM3
      can heterodimerize with GCKIII kinases (MST3, MST4, and STK25) to regulate
      cardiovascular development. Here, we provide direct experimental evidence to
      prove that CCM3 heterodimerizes with GCKIII in a manner structurally resembling
      the CCM3 homodimerization. Structural comparison revealed the mechanism and
      critical residues that drive CCM3-GCKIII heterodimerization versus
      homodimerization. A flexible linker was identified for CCM3, which mediates a
      large-scale conformational rotation of the FAT domain relative to the
      dimerization domain. The conformational flip over of FAT domain removes steric
      locking in the CCM3 homodimer and allows its disassembly and subsequent
      heterodimerization with GCKIII. CCM3 forms a stable complex with MST4 in vivo to
      promote cell proliferation and migration synergistically in a manner dependent on
      MST4 kinase activity. Collectively, our work offers a structural basis for
      further functional study.

PMID- 23541897
TI  - Calcification of a hydrophilic acrylic intraocular lens after Descemet-stripping
      endothelial keratoplasty: case report and laboratory analyses.
AB  - We describe the case of an 83-year-old woman who had uneventful
      phacoemulsification with implantation of a tripod hydrophilic acrylic intraocular
      lens (IOL). Because of postoperative corneal decompensation, 2 Descemet-stripping
      endothelial keratoplasty (DSEK) procedures were performed within 2 years. After
      the second procedure, the graft was not well attached, requiring an intracameral
      injection of air on day 3. Approximately 9 months later, opacification was
      observed on the anterior surface of the IOL, with a significant decrease in
      visual acuity. The IOL was explanted within the capsular bag. Laboratory analyses
      revealed granular deposits densely distributed in a round pattern within the
      margins of the capsulorhexis. Granules were located at the anterior
      surface/subsurface of the IOL and stained positive for calcium (alizarin red and
      von Kossa method). Scheimpflug photography revealed high levels of light
      scattering from the opacified area. Surgeons should be aware of possible
      localized calcification following DSEK procedures in pseudophakic patients with
      hydrophilic acrylic IOLs.

PMID- 23541898
TI  - Anterior capsule contraction and flare intensity in the early stages after
      cataract surgery in eyes with diabetic retinopathy.
AB  - PURPOSE: To evaluate the changes and relationship in the area of the anterior
      capsule opening (ACO) and anterior inflammation during the early stages after
      cataract surgery in diabetic patients with or without diabetic retinopathy (DR).
      SETTING: Department of Ophthalmology, University of Fukui, Fukui, Japan. DESIGN:
      Case-control study. METHODS: This study comprised diabetic patients without DR
      (non-DR group), diabetic patients with nonproliferative DR (DR group), and
      patients without diabetes mellitus (DM) (non-DM group) who had cataract surgery.
      The ACO area and aqueous flare intensity were measured using the EAS-1000 device
      and a laser flare-cell meter, respectively, 1 day, 1 week, and 1 and 3 months
      after surgery. RESULTS: The percentage of anterior capsule contraction (ACC) was
      significantly higher in the DR group than in the non-DR and non-DM groups 1 week
      and 1 and 3 months postoperatively (P<.01, Turkey-Kramer test). The aqueous flare
      intensity was significantly greater in the DR group than in the non-DR and non-DM
      groups 1 day, 1 week, and 1 and 3 months postoperatively (P<.01). Ordinary least
      squares regression analysis showed a significant positive correlation between
      aqueous flare intensity at 1 week and ACC 3 months after surgery in the non-DR
      group (P=.0178, R(2) = 0.173) and the DR group (P=.0018, R(2) = 0.308).
      CONCLUSION: Greater anterior flare levels 1 week after cataract surgery
      contributed to the extensive postoperative contraction of the ACO in diabetic
      patients, particularly those with DR.

PMID- 23541900
TI  - Impact of telmisartan on the inflammatory state in patients with coronary
      atherosclerosis--influence on IP-10, TNF-alpha and MCP-1.
AB  - BACKGROUND: Hypertension is one of the most prominent risk factors for coronary
      artery disease (CAD). Treatment of hypertension is therefore important for
      reducing cardiovascular events and the progression of atherosclerosis. Several
      treatment strategies are common in clinical practice for example the use of ACE
      blockers or angiotensin receptor II blockers (ARBs), so called sartans.
      Telmisartan, belonging to the class of ARBs, was shown to exert anti-inflammatory
      effects besides the blood pressure lowering. METHODS: In this work, two separate
      substudy groups of hypertensives were compared. 16 patients with arterial
      hypertension have been treated with telmisartan (initial 40 mg Kinzalmono(r)) for
      7.3 +/- 4.4 months. The telmisartan group was compared to a matched control group
      including 31 hypertensive patients without telmisartan treatment with a follow up
      period of 1.9 +/- 0.5 years. Serum samples from the beginning and the end of
      follow up were analyzed with Luminex(r) technology for 26 cytokines and
      chemokines. The baseline scores of coronary artery calcification (CAC) were
      gathered by multislice detector computer tomography. RESULTS: After 7 months of
      telmisartan treatment and 2 years in control patients most of the measured
      analytes did not change significantly. MCP-1 (P=0.001; P<0.001) was increased
      significantly in both telmisartan and control group. The relative decrease in IP
      10 and TNF-alpha levels was observed in telmisartan group, as opposed to the
      increase in control (telmisartan vs. control P=0.048; P=0.01). No linear rank
      correlation between measured analytes and the initial CAC was found. CONCLUSION:
      Telmisartan reduced blood pressure in patients with atherosclerosis and arterial
      hypertension within a short time period, whereas the inflammatory status of these
      patients remained largely unchanged. An involvement of telmisartan in the
      regulation of inflammatory and anti-inflammatory mediators in the context of CAD
      and CAC is possible, but cannot clearly be assumed based on the present findings.

PMID- 23541899
TI  - Implications for Interleukin-33 in solid organ transplantation.
AB  - Interleukin(IL)-33 is a member of the IL-1 cytokine family that has been
      attributed T helper (Th) type 2 immunity-promoting capacity. However, new studies
      indicate that IL-33 is a multifunctional protein that acts as
      transcriptional/signaling repressor, functions as an alarmin alerting the immune
      system to necrosis, as well as serves as a cytokine that targets cells expressing
      ST2, the IL-33 receptor. Interestingly, IL-33 is also emerging as a pleiotropic
      cytokine. Depending on the innate or adaptive immune cells targeted by IL-33, it
      can not only promote type 2, but also IFN-gamma dominated type 1 immunity. In
      addition, IL-33 expands regulatory T cells. In this review, we assimilate the
      current knowledge of IL-33 immunobiology and discuss how IL-33 may mediate such
      diverse roles in the immune response to pathogens and development of immune
      mediated pathologies. The function of IL-33 in shaping alloimmune responses to
      transplanted organs is poorly explored, but a particularly beneficial role of IL
      33 in experimental heart transplant models is summarized. Finally, given the
      implication of IL-33 in pathologies of the lung and intestine, we discuss how IL
      33 may contribute to the comparatively poor outcomes following transplantation of
      these two organs.

PMID- 23541901
TI  - The limits of deliberation in a perceptual decision task.
AB  - While it is commonly assumed that decisions taken slowly result in superior
      outcomes, is it possible that optimal decision making does not always require
      sacrificing speed? For odor categorization decisions, it was previously shown
      that rats use <300 ms regardless of difficulty, but these findings could be
      interpreted as a tradeoff of accuracy for speed. Here, by systematically
      manipulating the task contingencies, we demonstrate that this is the maximum time
      over which sampling time can improve accuracy. Furthermore, we show that decision
      accuracy increases at no temporal cost when rats can better anticipate either the
      identity of stimuli or the required timing of responses. These experiments
      suggest that uncertainty in odor category decisions arises from noise sources
      that fluctuate slowly from trial-to-trial rather than rapidly within trials and
      that category decisions in other species and modalities might likewise be
      optimally served by rapid choices.

PMID- 23541902
TI  - Ambient illumination toggles a neuronal circuit switch in the retina and visual
      perception at cone threshold.
AB  - VIDEO ABSTRACT: Gradual changes in the sensory environment can lead to abrupt
      changes in brain computations and perception. However, mechanistic understanding
      of the mediating microcircuits is missing. By sliding through light levels from
      starlight to daylight, we identify retinal ganglion cell types in the mouse that
      abruptly and reversibly switch the weighting of center and surround interactions
      in their receptive field around cone threshold. Two-photon-targeted recordings
      and genetic and viral tracing experiments revealed that the circuit element
      responsible for the switch is a large inhibitory neuron that provides direct
      inhibition to ganglion cells. Our experiments suggest that weak excitatory input
      via electrical synapses together with the spiking threshold in inhibitory cells
      act as a switch. We also reveal a switch-like component in the spatial
      integration properties of human vision at cone threshold. This work demonstrates
      that circuits in the retina can quickly and reversibly switch between two
      distinct states, implementing distinct perceptual regimes at different light
      levels.

PMID- 23541903
TI  - Atypical modulation of startle in women in face of aversive bodily sensations.
AB  - Eye blink startle magnitude is assumed to be higher in threatening contexts. A
      scarce amount of studies suggest that this does not hold true when startle is
      measured during perceived threats to homeostatic integrity. The present study was
      set up to describe the startle response pattern to a selection of interoceptive
      stimuli. Female subjects (N=36) were exposed once to 90 s of continued (1) cold
      pain, (2) inhalation of a gas mixture of 7.5% CO2, and (3) breathing against an
      inspiratory and expiratory resistive load. Each stimulus was preceded and
      followed by a 90 second period of rest, respectively labeled baseline and
      recovery. Even after correcting eye blink startle responses for habituation, a
      decreased startle amplitude was evident during these stimuli. Results suggest
      that startle amplitude during aversive stimulation is inversely correlated with
      perceived fearfulness for women, although further studies are necessary to
      corroborate this interpretation.

PMID- 23541904
TI  - Relationship between thyroid dysfunction and chronic kidney disease in community
      dwelling older adults.
AB  - OBJECTIVES: Renal function has been shown to be influenced by thyroid status in
      animal models and human studies. We aimed to assess the cross-sectional
      association between thyroid hormones and function with prevalence of chronic
      kidney diseases (CKD) in older adults. STUDY DESIGN: 1571 Blue Mountains Eye
      Study participants aged >= 60 years were analyzed in 2002-4. Thyroid dysfunction
      was defined using serum thyrotropin (TSH) screen, followed by serum free T4 (FT4)
      assessment. Baseline biochemistry including serum creatinine was measured.
      Moderate CKD was defined as estimated glomerular filtration rate (eGFR) <60
      ml/min/1.73 m(2). RESULTS: After adjusting for age, sex, receipt of pension
      payment, body mass index, smoking, hypertension and diabetes, persons with any
      thyroid dysfunction (hyperthyroidism or hypothyroidism) had 84% higher likelihood
      of having CKD, odds ratio, OR, 1.84 (95% confidence intervals, CI, 1.03-3.31).
      Participants in the highest versus lowest quartile (reference) of serum TSH and
      FT4 had a significantly greater odds of prevalent CKD, OR 1.82 (95% CI 1.22
      2.71), and OR 1.64 (95% CI 1.10-2.45), respectively. Similarly, among
      participants not receiving treatment for their thyroid dysfunction (n=1329),
      those in the third and fourth quartiles of serum TSH had significantly greater
      odds of having prevalent CKD, OR 1.83 (95% CI 1.15-2.92) and OR 1.96 (95% CI 1.23
      3.13), respectively, Ptrend=0.001. Significant associations were not observed
      between type of thyroid dysfunction (hyperthyroidism or hypothyroidism) and
      prevalent CKD. CONCLUSIONS: Increasing serum TSH was associated with a greater
      likelihood of prevalent CKD among older adults, independent of the influence of
      age, diabetes and hypertension.

PMID- 23541905
TI  - Long term consequences of the female athlete triad.
AB  - In the past 40 years, female sports participation, particularly at the high
      school level, has significantly increased. Physical activity in females has
      numerous positive benefits, including improved body image and overall health.
      Unfortunately, a select population of exercising females may experience symptoms
      related to the female athlete triad, which refers to the interrelatedness of
      energy availability, menstrual function, and bone mineral density. Clinically,
      these conditions can manifest as disordered eating behaviors, menstrual
      irregularity, and stress fractures. Triad symptoms are distributed along a
      spectrum between optimal health and disease; all of the components of the triad
      may not be affected simultaneously. The female athlete triad was first identified
      in 1992. Since that time, a vast amount of research related to the
      identification, management and prevention of this condition has been published.
      More recently, research related to the long term effects of triad components has
      come into light. Women who were diagnosed with female athlete triad syndrome as
      adolescents and young adults in the 1990s are now in their 30s and 40s; negative
      long term effects of the female athlete triad, such as low bone mineral density,
      are now starting to manifest. Women of all ages should be assessed for triad
      components during routine annual physical examinations; appropriate measures to
      treat any current triad components should be implemented. In addition, women in
      their 30s, 40s and early 50s should be screened for a history of the female
      athlete triad. Multidisciplinary management of these conditions is strongly
      recommended.

PMID- 23541906
TI  - Interaction of choline salts with artificial biological membranes: DSC studies
      elucidating cellular interactions.
AB  - To better understand the relationship between the relative cytotoxicity of
      diluted ionic liquids and their specific interaction with biological membranes,
      the thermotropic behavior of model lipid membrane systems formulated in a series
      of choline based organic salts was investigated. Unilamellar vesicles prepared
      from dipalmitoylphosphatidylcholine were exposed to a series of choline phosphate
      salts at a concentration of 10mM at pH7.40, and the gel to liquid-crystalline
      state transition was examined using differential scanning calorimetry. The
      choline salts that were observed to have a low relative toxicity in previous
      studies induced minimal changes in the lipid phase transition behavior of these
      model membranes. In contrast, the salts choline bis(2,4,4
      trimethylpentyl)phosphinate and choline bis(2-ethylhexyl)phosphate, both of which
      were observed to have high relative toxicity, caused distinct disruptions in the
      lipid phase transition behavior, consistent with penetration of the salts into
      the acyl chains of the phospholipids. choline bis(2,4,4
      trimethylpentyl)phosphinate reduced the Tm and enthalpy of the main transition of
      dipalmitoylphosphatidylcholine while choline bis(2-ethylhexyl)phosphate induced
      the equilibration of alternate phases.

PMID- 23541907
TI  - Metabolic engineering of Clostridium acetobutylicum ATCC 824 for the high-yield
      production of a biofuel composed of an isopropanol/butanol/ethanol mixture.
AB  - Clostridium acetobutylicum was metabolically engineered to produce a biofuel
      consisting of an isopropanol/butanol/ethanol mixture. For this purpose, different
      synthetic isopropanol operons were constructed and introduced on plasmids in a
      butyrate minus mutant strain (C. acetobutylicum ATCC 824
      Deltacac15DeltauppDeltabuk). The best strain expressing the isopropanol operon
      from the thl promoter was selected from batch experiments at pH 5. By further
      optimizing the pH of the culture, a biofuel mixture with almost no by-products
      was produced at a titer, a yield and productivity never reached before, opening
      the opportunities to develop an industrial process for alternative biofuels with
      Clostridial species. Furthermore, by performing in vivo and in vitro flux
      analysis of the synthetic isopropanol pathway, this flux was identified to be
      limited by the [acetate](int) and the high Km of CoA-transferase for acetate.
      Decreasing the Km of this enzyme using a protein engineering approach would be a
      good target for improving isopropanol production and avoiding acetate
      accumulation in the culture medium.

PMID- 23541908
TI  - The effect of ultrasonic and HNO3 treatment of activated carbon from fruit stones
      on capacitive and pseudocapacitive energy storage in electrochemical
      supercapacitors.
AB  - The effect of ultrasonic treatment and modification with nitric acid of activated
      carbon obtained from fruit stones, on the parameters of electric double-layer
      (EDL) as well as on farad-volt characteristics of its boundary with electrolyte
      7.6 m KON, 4 m KI and 2 m ZnI2 aqueous solutions has been studied by means of
      precision porometry, cyclic voltamperometry, electrochemical impedance
      spectroscopy and computer simulation methods. It is shown that HNO3 treatment
      results in an increase of the electrostatic capacitance up to 202 F/g in 7.6 m
      KON-solution as well as pseudocapacitance up to 1250 F/g in 4 m KI. This increase
      is supposed to be related both with hydrophilicity and with an increase of the
      density of states on Fermi level. The ultrasonic treatment enables one to
      significantly increase (more than 200 times) the density of states on Fermi level
      which in turn causes both quantitative and qualitative changes in farad-volt
      dependences. A hybrid supercapacitor with specific capacitance of 1100 F/g and
      specific energy of 49 Wh/kg per active mass of two electrodes was developed.

PMID- 23541909
TI  - Risk of colorectal high-grade dysplasia and cancer in a prospective observational
      cohort of patients with inflammatory bowel disease.
AB  - BACKGROUND & AIMS: There is an unclear risk of colonic high-grade dysplasia (HGD)
      and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD)
      treated with immunosuppressants. We analyzed data on CRC development among
      patients with IBD enrolled in the observational cohort Cancers et Surrisque
      Associe aux Maladies Inflammatoires Intestinales En France (CESAME). METHODS: We
      followed and collected data from 19,486 patients with IBD (60.3% with Crohn's
      disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and
      June 2005, and followed them until December 2007. When the study began, 2841
      patients (14.6%) were characterized as having long-standing extensive colitis
      (ie, >10 years and involving >=50% of the colon). Early lesions (HGD and CRC)
      were defined as those diagnosed within 10 years after diagnosis of IBD. RESULTS:
      Thirty-seven patients developed CRC during the follow-up period, and 20 developed
      colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD
      patients (95% confidence interval [CI]: 1.5-3.0; P < .0001), 7.0 for patients
      with long-standing extensive colitis (95% CI: 4.4-10.5; P < .001), and 1.1 for
      patients without long-standing extensive colitis (95% CI: 0.6-1.8; P = .84).
      Among patients with long-standing extensive colitis, the multivariate adjusted
      hazard ratio for colorectal HGD and cancer was 0.28 for those who received
      thiopurines compared with those who never received thiopurine therapy (95% CI:
      0.1-0.9; P = .03). Twenty-two patients developed early lesions; 7 of these were
      related to IBD, based on histologic analysis. CONCLUSIONS: Patients with IBD and
      long-standing extensive colitis are at increased risk for CRC, although the risk
      is lower among patients receiving thiopurine therapy. Patients without long
      standing extensive colitis have a risk for CRC similar to that of the general
      population, but they can develop IBD-related lesions within 10 years after
      diagnosis of IBD.

PMID- 23541910
TI  - Classical cadherins control survival through the gp130/Stat3 axis.
AB  - Stat3 (Signal Transducer and Activator of Transcription-3) is activated by a
      number of receptor and nonreceptor tyrosine kinases. We recently demonstrated
      that engagement of E-cadherin, a calcium-dependent, cell to cell adhesion
      molecule which is often required for cells to remain tightly associated within
      the epithelium, also activates Stat3. We now examined the effect of two other
      classical cadherins, cadherin-11 and N-cadherin, whose expression often
      correlates with the epithelial to mesenchymal transition occurring in metastasis
      of carcinoma cells, upon Stat3 phosphorylation and activity. Our results indicate
      that engagement of these two cadherins also, can trigger a dramatic surge in
      Stat3 activity. This activation occurs through upregulation of members of the IL6
      family of cytokines, and it is necessary for cell survival, proliferation and
      migration. Interestingly, our results also demonstrate for the first time that,
      in sharp contrast to Stat3, the activity of Erk (Extracellular Signal Regulated
      kinase) was unaffected by cadherin-11 engagement. Further examination indicated
      that, although IL6 was able to activate Erk in sparsely growing cells, IL6 could
      not induce an increase in Erk activity levels in densely growing cultures. Most
      importantly, cadherin-11 knock-down did allow Erk activation by IL6 at high
      densities, indicating that it is indeed cadherin engagement that prevents Erk
      activation by IL6. The fact that the three classical cadherins tested so far, E
      cadherin, N-cadherin and cadherin11, which are present in essentially all
      tissues, actually activate Stat3 regardless of their role in metastasis, argues
      for Stat3 as a central survival, rather than invasion factor.

PMID- 23541912
TI  - Maternal dietary patterns during pregnancy and child internalising and
      externalising problems. The Generation R Study.
AB  - BACKGROUND & AIMS: Maternal nutritional factors during pregnancy have been linked
      to foetal brain development and subsequent offspring behaviour. Less is known
      about associations between maternal dietary patterns and offspring behaviour.
      METHODS: Within a population-based cohort, we assessed maternal diet using a food
      frequency questionnaire. Three dietary patterns were derived by means of
      Principal Component Analysis. Child internalising (emotionally reactive,
      anxious/depressed or withdrawn, having somatic complaints) and externalising
      problems (inattention, aggression) were assessed with the Child Behaviour
      Checklist at 1.5, 3 and 6 years in 3104 children. We assessed the association of
      maternal Mediterranean, Traditionally Dutch and Confectionary dietary pattern
      during pregnancy with child internalising and externalising problems. RESULTS:
      After adjustment, the Mediterranean diet was negatively associated (ORper SD in
      Mediterranean score = 0.90, 95% CI: 0.83-0.97) and the Traditionally Dutch diet
      was positively associated with child externalising problems (ORper SD in
      Traditionally Dutch score = 1.11, 95% CI: 1.03-1.21). Neither diet was associated
      with internalising problems. CONCLUSIONS: Both low adherence to the Mediterranean
      diet and high adherence to the Traditionally Dutch diet during pregnancy are
      associated with an increased risk of child externalising problems. Further
      research is needed to unravel the effects of nutrient interplay during and after
      pregnancy on child behavioural development.

PMID- 23541913
TI  - Fatty acids in plasma, white and red blood cells, and tissues after oral or
      intravenous administration of fish oil in rats.
AB  - BACKGROUND & AIMS: The importance of route of administration of omega-3 (n-3)
      polyunsaturated fatty acids (PUFA) (oral vs intravenous (iv)) is not clear. We
      determined the relative concentrations of fatty acids in plasma
      phosphatidylcholine (PC), red blood cells (RBC), white blood cells (WBC) and
      several tissues after short-term oral or iv administration of soybean oil (SO) or
      fish oil (FO). METHODS: Wistar rats (n = 6/group) received saline, FO, or SO by
      gavage or saline, FO based-lipid emulsion (FLE), or SO based-lipid emulsion (SLE)
      iv. The oils were provided at 0.2 g/kg/day for three consecutive days. The
      animals were sacrificed 24 h after the last administration, blood was collected
      for plasma, WBC and RBC separation and tissues removed. Fatty acids were analysed
      by gas chromatography. RESULTS: FO resulted in higher eicosapentaenoic acid (EPA)
      in plasma PC and liver than the control. FLE resulted in higher EPA,
      docosahexaenoic acid (DHA) and total n-3 PUFA in plasma PC, WBC and liver than
      both the control and SLE groups. EPA, DHA and total n-3 PUFA were higher in the
      heart with FLE compared with SLE. Individual and total n-3 PUFA were higher in
      plasma PC, WBC, liver and heart with FLE than with FO given by gavage.
      CONCLUSION: Short-term iv administration of n-3 PUFA appears to be more effective
      at increasing EPA and DHA status in plasma, WBC, liver and heart than oral
      administration. This might be important for rapid treatment with n-3 PUFA.

PMID- 23541911
TI  - A dynamic auditory-cognitive system supports speech-in-noise perception in older
      adults.
AB  - Understanding speech in noise is one of the most complex activities encountered
      in everyday life, relying on peripheral hearing, central auditory processing, and
      cognition. These abilities decline with age, and so older adults are often
      frustrated by a reduced ability to communicate effectively in noisy environments.
      Many studies have examined these factors independently; in the last decade,
      however, the idea of an auditory-cognitive system has emerged, recognizing the
      need to consider the processing of complex sounds in the context of dynamic
      neural circuits. Here, we used structural equation modeling to evaluate the
      interacting contributions of peripheral hearing, central processing, cognitive
      ability, and life experiences to understanding speech in noise. We recruited 120
      older adults (ages 55-79) and evaluated their peripheral hearing status,
      cognitive skills, and central processing. We also collected demographic measures
      of life experiences, such as physical activity, intellectual engagement, and
      musical training. In our model, central processing and cognitive function
      predicted a significant proportion of variance in the ability to understand
      speech in noise. To a lesser extent, life experience predicted hearing-in-noise
      ability through modulation of brainstem function. Peripheral hearing levels did
      not significantly contribute to the model. Previous musical experience modulated
      the relative contributions of cognitive ability and lifestyle factors to hearing
      in noise. Our models demonstrate the complex interactions required to hear in
      noise and the importance of targeting cognitive function, lifestyle, and central
      auditory processing in the management of individuals who are having difficulty
      hearing in noise.

PMID- 23541914
TI  - [Rationale for the use of long-acting injectable risperidone: a survey of French
      psychiatrists].
AB  - INTRODUCTION: Poor adherence is a major concern for the effectiveness of
      antipsychotic treatment in patients with schizophrenia. In particular, compliance
      problems constitute a poor prognostic factor for this disorder due to increasing
      risk of relapse and hospitalization. As maintaining antipsychotic therapy is a
      key element to prevent relapse, the use of depot preparations is therefore
      considered as a useful therapeutic option since it prevents covert non-adherence.
      When compared with neuroleptics, novel antipsychotic agents are also better
      tolerated by patients. In this study, the rationale for the use of long-acting
      injectable risperidone combining the benefits of novel antipsychotic agent and
      depot preparation is investigated in patients with psychosis. A secondary
      objective of the study is to assess the level of therapeutic adherence and to
      confirm the role of its key determinants. METHODS: An observational survey
      assessed the time and reasons to switch to long-acting risperidone in 1887
      hospitalized and community-dwelling patients with psychosis (61.6% schizophrenia)
      defined by the CIM-10, and treated by 399 psychiatrists with oral risperidone for
      a recent acute episode. In a cross-sectional study performed under real-life
      conditions, treatment adherence was assessed by patients themselves using the
      Medication Adherence Questionnaire (MAQ) and therapeutic alliance was assessed by
      the 4-Point Alliance Scale (4-PAS). Psychiatrists assessed treatment acceptance
      using the Compliance Rating Scale (CRS), disease severity using the CGI, and
      insight using the G12 item from the Positive and Negative Syndrome Scale (PANSS).
      RESULTS: In the population studied, disorder severity (CGI) was defined as
      "moderate to marked" in 67.7% and "severe or among the most severe" for 21.1%.
      Insight (PANSS G12) was defined as normal for 36.6% of patients, moderate for
      34.8% and low for 28.6%. The mean time to medication switch was 8 weeks after the
      start of care of the acute episode. The two main reasons to start the long-acting
      injectable risperidone were related to non-compliance with oral antipsychotic
      treatment (92.4%) and intention to improve efficacy (86.4%). Maintenance of a
      good therapeutic alliance (70.3%) and treatment tolerability (54.6%) were also
      often cited. For psychiatrists, 41.6% of patients demonstrated reticence or
      active reluctance to treatment. Therapeutic compliance (MAQ) for oral medication
      before the long-acting injectable risperidone was started was estimated as "mild"
      for 53.1% (n=852) of patients. Poor adherence strongly correlated with low
      insight (P<0.001) and with a disorder estimated as "severe" (P<0.001).
      Therapeutic alliance was higher for patients with a better level of treatment
      acceptance assessed by psychiatrists (P<0.001) and with a higher compliance with
      MAQ estimated by patients (P<0.001). Therapeutic alliance was lower for patients
      with a disorder defined as "severe" (P<0.001) and with poor insight (P<0.001).
      CONCLUSION: In this French survey, the two main reasons for psychiatrists to
      start long-acting injectable risperidone were related to non-compliance with oral
      antipsychotic treatment and with the desire to improve therapeutic efficacy. In
      accordance with results of previous studies, insight and therapeutic alliance
      were found to be associated with poor compliance. The main goal in the treatment
      of psychotic disorders is to obtain a functional remission and to reduce the
      incidence of relapse. Considering its improved efficiency and reduced dependence
      on patient compliance, the use of long-acting injectable risperidone is
      recommended as a useful therapeutic strategy.

PMID- 23541915
TI  - [Family violence].
AB  - INTRODUCTION: Family violence is a serious public health problem, the scale of
      which is seriously increasing in Morocco. Although it has existed for a long
      time, we ignore the real characteristics of this plague in our country; our work
      consisted in an epidemiological approach of family violence in Marrakech during
      2006. METHOD: After elaborating a questionnaire, which allows the study of the
      demographic and social profile of the families, the study of violence exercised
      in the family and the evaluation of the depression in the women, we led an
      inquiry amongst 265 women. RESULTS: Analysis of the results obtained has allowed
      us to underline the following characteristics: 16.6% of the women in our sample
      had been physically beaten; the young age is a risk factor; the age range most
      affected by violence is in women between the ages of 30 and 40 and which
      represent 39% of the battered women; domestic violence touches all the social,
      economic and cultural classes: in our study, 63% of the women having undergone
      violence were housewives, 25% were managers and 3% senior executives; family
      problems were the most important cause of violence in our study, representing
      32.32%. Requests for money was the cause in 11.3% of the cases, and imposed
      sexual relations were found in 6.8% of the cases; alcoholism is an aggravating
      factor of family violence; 27.3% of the spouses who assaulted their wives were
      drunk; 52% of the assaulted women were victims of violence in childhood and 36%
      had been witness to their father's violence; in 63.6% of the cases of violence,
      the children were witnesses, and in 25% of the cases the children were victims of
      violence at the same time as their mothers; 50% of the women victims of violence
      did not react, while 38.6% left home, and 9.1 filed for divorce. Thirty-two
      percent of the assaulted woman had been traumatised by the aggression; the
      association of depression and violence was very high, 343% of the battered women
      in our study suffered from severe depression. CONCLUSION: This work underlines
      the necessity of an urgent intervention in order to limit the extension of this
      plague and its consequences.

PMID- 23541916
TI  - [A cross-sectional study of trait-anxiety in a group of 111 intellectually gifted
      children].
AB  - INTRODUCTION: Intellectually gifted children are often thought to display a high
      risk for psychopathology. However, this assertion has received only few direct
      arguments to date, and there is in fact a lack of knowledge on this subject. The
      aim of this study was to compare trait-anxiety - which is considered as a
      sensitive and early indicator of psychoaffective difficulties in children - in
      intellectually gifted children to the norm. METHODS: One hundred and eleven
      children aged 8 to 12 and with an intellectual quotient (IQ) higher than 129
      participated in the study. They were recruited in a hospital department of child
      and adolescent psychiatry and through psychologists' private practice, where they
      attended consultation because of academic underachievement and/or social
      maladjustment. All the children were examined by trained psychiatrists and
      psychologists: none had a present or past medical or psychiatric condition and,
      additionally, none had an elevated score on the French version of the Children's
      Depressive Rating Scale Revised (Moor & Mack, 1982). Parents filled in a
      questionnaire for the collection of socio-demographic data and children answered
      the French version of the Revised-Children's Manifest Anxiety Scale (R-CMAS;
      Reynolds, 1999), a 37-items self-assessment of trait-anxiety, the psychometric
      properties of which have been validated in children with high IQ. DATA ANALYSIS:
      Mean scores and subscores on the R-CMAS in the whole studied group and as a
      function of gender and age were compared to French normative data (Reynolds,
      1999) by calculation of 95% confidence intervals; subgroups were compared using
      Student's t-tests. Proportions of children who's score and subscores exceeded
      anxiety cut-off norms were compared to normative data using chi-square tests.
      Statistical significance was considered at the P<0.05 level. RESULTS: The studied
      group comprised mainly boys, and members of a sibling. Parents mainly lived as
      man and wife, had high academic levels, and had a professional activity. The
      confidence intervals of the R-CMAS scores and subscores all comprised their
      normative value, which denotes that no difference was statistically significant.
      Comparisons for age and gender showed no significant difference. Proportions of
      results exceeding the cut-off scores and subscores did not significantly differ
      from the norms. DISCUSSION: General and dimensional trait-anxiety levels in the
      studied group were comparable to normative data. These results are in accordance
      with previous studies of trait-anxiety in children and adolescents with high IQ,
      which all showed normal or decreased levels. These findings do not corroborate
      the hypothesis that intellectual giftedness constitutes a risk factor for
      psychopathology. LIMITS: The studied group was a clinical one, which could limit
      the generalisation of the results. However, mental disorders were ruled out, and
      the psychometric and socio-demographic characteristics of the group were in
      keeping with those described for the general population of gifted children.
      Moreover, considering that participant children displayed academic
      underachievement and/or social maladjustment, it can be supposed that their
      anxiety levels were not lower than those in the general population of gifted
      children. Secondly, the potentially confusing effect of socio-demographic
      variables (underrepresentation of low socio-economic levels and single-parent
      families) could not be statistically taken into account, due to the absence of a
      specific control group. CONCLUSION: Intellectually gifted children seem not to
      display increased trait-anxiety. However, further studies are necessary to
      investigate psychological functioning in gifted children and their risk for
      psychopathology.

PMID- 23541917
TI  - [Acute pancreatitis induced by valproic acid].
AB  - INTRODUCTION: We describe the case of an adult man aged 49, without personal
      antecedents, or family psychiatric history, treated for bipolar disorder since
      1995 and stabilised in the last 8 years by valproic acid, who presented in
      January 2010 an acute drug-induced pancreatitis. Drug-induced pancreatitis has
      been described since 1955. It may be induced by more than 260 various molecules,
      as well as by valproic acid, which remains underreported in the literature
      because there is a problem of imputability. BACKGROUND: The prevalence of acute
      drug-induced pancreatitis is set between 1 and 2 %. However, it must remain as an
      exclusion diagnosis after conducting an exhaustive etiological investigation that
      will, notably, eliminate bilary and alcoholic causes. The most incriminated drugs
      are the inhibitors of the conversion enzyme, sulfa drugs, non-steroidal anti
      inflammatory, diuretics and anticonvulsants, including valproic acid. In Tunisia,
      the prescription of valproic acid is increasing in bipolar disorder therapy
      because it is known for its weak toxicity and easy handling. CASE REPORT: The
      case of our patient, who suffers from an acute Balthazar stage C pancreatitis
      with severe evolution after the drug was stopped, the imputability of valproic
      acid was considered strong and the collegial decision between the surgery,
      pharmacovigilance and psychiatry services maintained the drug-induced origin and
      consequently stopped the valproic acid. DISCUSSION: This case supports the idea
      that acute pancreatitis may be induced by valproic acid, even after a
      prescription lasting for a long period of time, it has no predictable factors and
      is totally independent of the drug-related dose and of depakine blood levels.
      There are no predictive factors to the present day, but the evolution is
      generally good except in rare cases where it may be dangerous. This leads us to
      think of bipolar patients who are found within weak grounds, such as alcoholics,
      cancer and HIV positive patients.

PMID- 23541918
TI  - [Anorexia nervosa in the light of neurocognitive functioning: New theoretical and
      therapeutic perspectives].
AB  - INTRODUCTION: Anorexia nervosa is a serious psychiatric disorder, for which very
      few validated therapeutic strategies exist. The specific sociocognitive style of
      anorexic patients has already been described in the 1960s: it involves a concrete
      style with abstraction difficulties. Current neuropsychological tests have
      contributed to a more precise definition of these difficulties.
      NEUROPSYCHOLOGICAL DATA: IS THERE A SPECIFIC COGNITIVE PROFILE?: Contrary to
      common beliefs, these patients' intellectual performances are not superior to
      those of the general population. However, detailed comparisons of profiles on the
      Weschler Scales suggest difficulties in synthesizing information and better
      abilities in concrete problem solving. EXCESSIVE ATTENTION TO DETAILS: The
      dominant hypothesis concerning the attentional dimension is the existence of a
      weakness in central coherence, resulting in superior detail processing and a
      weakness in global integration. This trend appears to be stable even after the
      normalization of nutritional status. IMPAIRED COGNITIVE FLEXIBILITY: The
      impairment of set-shifting abilities leads to rigidity, expressed by
      inflexibility and perseveration, both in reasoning and behaviour. This reduced
      cognitive flexibility appears to persist after recovery, and may constitute a
      familial trait. In addition, this likely endophenotype seems to be independent
      from obsessional traits. CONTROVERSIAL SOCIAL SKILL: Alexithymia is frequently
      described in anorexic individuals. It is the verbal description of feelings which
      seems to be particularly impaired. It may explain underlying difficulties in
      empathy. Indeed, these subjects have lower scores on emotional tests drawn from
      the theory of mind. These cognitive abnormalities are well documented in
      pervasive developmental disorders. NEUROANATOMICAL DATA: NEUROIMAGING IN SUPPORT
      OF LIMBIC AND FRONTO-STRIATAL ABNORMALITIES: Evidence from neuroimaging suggests
      abnormalities in cortical and subcortical structures, involving the temporal and
      orbito-frontal lobes. Various functional hypotheses are formulated, involving
      fronto-striatothalamic circuits, amygdala or insula. IS ANOREXIA NERVOSA A
      DEVELOPMENTAL DISORDER?: Pervasive developmental disorders are over-represented
      among anorexic subjects in comparison to the general population. Conversely,
      restrictive and selective eating disorders are more frequent among individuals
      presenting an autistic spectrum disorder. THERAPEUTIC IMPLICATIONS AND FUTURE
      DIRECTIONS: In view of the common cognitive and neuroanatomical data that are
      found in anorexia nervosa and neurodevelopmental disorders, we adhere to the
      hypothesis that anorexia nervosa may be similar to a neurodevelopmental disorder.
      Clinical observations suggest that this hypothesis may be especially relevant in
      the early forms of anorexia nervosa. These cognitive data confirm the potential
      relevance of new therapeutic modalities such as cognitive remediation. Initial
      results from its application to anorexia nervosa seem promising. CONCLUSION: A
      review of the recent literature highlights the possible existence of a
      developmental impairment of cortical and subcortical structures, associated with
      specific abnormalities in cognitive development such as a weakness in central
      coherence, reduced set-shifting ability and poor social skills. On this basis,
      cognitive remediation may be a promising therapeutic innovation.

PMID- 23541919
TI  - [Atypical depression: Clinical perspectives].
AB  - OBJECTIVE: This paper examines whether atypical depression is still a valid
      entity as a diagnosis subtype in the light of publications with most recent
      antidepressants. METHOD: First, we present the origins of the diagnosis sub
      specification of atypical depression, which is based on a different drug response
      to tricyclic antidepressants and mono amino oxydase inhibitors. Secondly, we
      discuss the different definitions that can be found for the terms of atypical
      depression. We present more specifically the definition of atypical depression as
      it is described in the DSM-IV, with its most important criterion: mood
      reactivity. Then we present a review of scientific publications questioning
      atypical depression validity as a clinical syndrome (based on medline
      researches). We will see whether this diagnosis is still relevant with the latest
      drugs used to treat mood disorders. A special focus is made on the link between
      atypical depression and bipolar disorder, based on Benazzi's work. RESULTS: Most
      of publications confirm that atypical depression is a valid syndrome regarding
      first antidepressants clinical trials. Nevertheless, more studies with the latest
      antidepressants and atypical antipsychotics are needed to confirm this
      hypothesis. The link between atypical depression and bipolar disorders seems to
      be quite strong although it requires further investigations. DISCUSSION: There
      are very few double-blind drug trials focusing on atypical depressions and
      results need to be confirmed by trials with new drugs. Moreover, we regret that
      there are no studies including cerebral imagery. More studies are also needed on
      neurobiology and psychotherapy specificity. CONCLUSION: Atypical depression is
      still a useful concept, because of its specific clinical presentation, evolution
      and treatments, even if more studies should be done. Atypical depression could
      also be useful to diagnose more easily some bipolar disorders and should help
      clinicians to focus more on suicidal risks and addiction evaluation for these
      patients, considering the mood reactivity and the link with bipolar disorder. To
      conclude, we propose that atypical depression should still figure in the future
      DSM-V for these different reasons.

PMID- 23541920
TI  - Production of seven monoclonal equine immunoglobulins isotyped by multiplex
      analysis.
AB  - Horses have 11 immunoglobulin isotypes: IgM, IgD, IgA, IgE, and seven IgG
      subclasses designated as IgG1-IgG7, each of which are distinguished by separate
      genes encoding the constant heavy chain regions. Immunoglobulin (Ig) isotypes
      have different functions during the immune response and pathogen-specific
      isotypes can be used as indicators for immunity and protection from disease. In
      addition to existing monoclonal antibodies to various equine Igs, quantification
      of the individual isotypes requires pure isotype standards. In this report, we
      describe a fusion between X63-Ag8.653 mouse myeloma cells and horse PBMC to
      create equine-murine heterohybridomas. Initial screening for Ig production was
      performed by ELISA. Further testing was performed by a new 5-plex fluorescent
      bead-based assay able to simultaneously detect equine IgM, IgG1, IgG4/7, IgG5,
      and IgG6. Production of IgG3 and IgE was tested by separate bead assays. Seven
      stable heterohybridoma clones producing monoclonal equine IgM, IgG1, IgG3,
      IgG4/7, IgG5, IgG6 and IgE were created. Purified Ig isotypes were then tested by
      SDS-PAGE. The pure, monoclonal equine Ig isotypes and the new equine Ig multiplex
      testing developed here are valuable tools to quantify antibody responses and to
      accurately determine individual isotypes concentrations in horses.

PMID- 23541921
TI  - Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human
      embryonic stem cell self-renewal.
AB  - The embryonic stem cell (ESC) transcriptional and epigenetic networks are
      controlled by a multilayer regulatory circuitry, including core transcription
      factors (TFs), posttranscriptional modifier microRNAs (miRNAs), and some other
      regulators. However, the role of large intergenic noncoding RNAs (lincRNAs) in
      this regulatory circuitry and their underlying mechanism remains undefined. Here,
      we demonstrate that a lincRNA, linc-RoR, may function as a key competing
      endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and
      Nanog. We show that linc-RoR shares miRNA-response elements with these core TFs
      and that linc-RoR prevents these core TFs from miRNA-mediated suppression in self
      renewing human ESC. We suggest that linc-RoR forms a feedback loop with core TFs
      and miRNAs to regulate ESC maintenance and differentiation. These results may
      provide insights into the functional interactions of the components of genetic
      networks during development and may lead to new therapies for many diseases.

PMID- 23541923
TI  - Effect of infection with BHV-1 on peripheral blood leukocytes and lymphocyte
      subpopulations in calves with subclinical BVD.
AB  - Bovine viral diarrhea virus (BVDV) and bovine herpesvirus-1 (BHV-1) are important
      cattle pathogens that induce a broad immunosuppression on cell-mediated immune
      response on its own participating in the bovine respiratory disease complex
      (BRDC). The aim of our study was to evaluate the quantitative changes in
      immunocompetent cells in healthy calves and calves with subclinical bovine viral
      diarrhea (BVD), both inoculated with BHV-1. Total leukocyte counts exhibited
      changes mainly in neutrophils and lymphocytes that can contribute to the BVDV
      immunosuppression, thus accounting for some of the intergroup differences.
      Monocytes did not display numerical changes in either group. Regarding lymphocyte
      subpopulations, even though CD4+ T lymphocytes and B cells were depleted around 4
      dpi in both infected groups, the main difference observed between both groups was
      in CD8+ T cells which displayed an earlier depletion in BVDV inoculated calves
      that can promote a greater BHV-1 dissemination, thus aggravating the course of
      the disease.

PMID- 23541922
TI  - Hec1-dependent cyclin B2 stabilization regulates the G2-M transition and early
      prometaphase in mouse oocytes.
AB  - The functions of the Ndc80/Hec1 subunit of the highly conserved Ndc80 kinetochore
      complex are normally restricted to M phase when it exerts a pivotal kinetochore
      based role. Here, we find that in mouse oocytes, depletion of Hec1 severely
      compromises the G2-M transition because of impaired activation of cyclin
      dependent kinase 1 (Cdk1). Unexpectedly, impaired M phase entry is due to
      instability of the Cdk1-activating subunit, cyclin B2, which cannot be covered by
      cyclin B1. Hec1 protects cyclin B2 from destruction by the Cdh1-activated
      anaphase-promoting complex (APC(Cdh1)) and remains important for cyclin B2
      stabilization during early M phase, required for the initial stages of
      acentrosomal spindle assembly. By late M phase, however, Hec1 and cyclin B2
      become uncoupled, and although Hec1 remains stable, APC(Cdc20) triggers cyclin B2
      destruction. These data identify another dimension to Hec1 function centered on M
      phase entry and early prometaphase progression and challenge the view that cyclin
      B2 is completely dispensable in mammals.

PMID- 23541924
TI  - Association of BoLA DRB3 alleles with variability in immune response among the
      crossbred cattle vaccinated for foot-and-mouth disease (FMD).
AB  - Polymorphism of bovine leukocyte antigen (BoLA) DRB3 gene is being intensively
      investigated for potential association with economically important diseases of
      cattle. Accordingly, we investigated the association of DRB3 Exon 2 polymorphism
      as evidenced by the variation in the binding pockets with variability in immune
      response to inactivated trivalent (O, A and Asia1) foot and mouth disease virus
      (FMDV) vaccine in a closed population of crossbred cattle. Antibody titer of >=
      1.8 was set as the cut off value to distinguish the protected (>= 1.8) and
      unprotected (<1.8) animals. Eleven different alleles of over 3% frequency were
      detected in the population. We found that DRB3 alleles 0201, 0801 and 1501 always
      ranked high for protective immune response whereas alleles 0701, 1103 and 1101
      consistently ranked low for unprotected immune response for all the three
      serotypes. Rank correlation of DRB3 alleles among the three serotypes was
      positive, high in magnitude and statistically significant (P<0.05). Logistic
      regression analysis revealed that odds of protection from the vaccine were
      highest for all the three serotypes if allele (*)1501 was present and
      strengthened the results of allele ranking. Predicted amino acid substitution in
      the peptide binding pockets revealed that all the important sites had high Wu
      Kabat index. Similarly, specific residues in pockets were crucial for immune
      response to FMD vaccine. There were specific substitutions in un-protected
      alleles such as absence of acidic amino acids substituted by basic amino acid at
      beta71, presence of non-polar cysteine or basic histidine at beta30 and presence
      of polar tyrosine at beta37. From the observations, we hypothesize that the
      substitutions lead to unique conformational changes in the protein products of
      the studied alleles that would associate with the protective or unprotective
      antibody response to FMDV vaccine. The knowledge has potential implications in
      future selection programs if integrated with the complete BoLA haplotype details
      and production traits of the herd.

PMID- 23541925
TI  - Computing with networks of spiking neurons on a biophysically motivated floating
      gate based neuromorphic integrated circuit.
AB  - Results are presented from several spiking network experiments performed on a
      novel neuromorphic integrated circuit. The networks are discussed in terms of
      their computational significance, which includes applications such as arbitrary
      spatiotemporal pattern generation and recognition, winner-take-all competition,
      stable generation of rhythmic outputs, and volatile memory. Analogies to the
      behavior of real biological neural systems are also noted. The alternatives for
      implementing the same computations are discussed and compared from a
      computational efficiency standpoint, with the conclusion that implementing neural
      networks on neuromorphic hardware is significantly more power efficient than
      numerical integration of model equations on traditional digital hardware. 

PMID- 23541926
TI  - Learning the pseudoinverse solution to network weights.
AB  - The last decade has seen the parallel emergence in computational neuroscience and
      machine learning of neural network structures which spread the input signal
      randomly to a higher dimensional space; perform a nonlinear activation; and then
      solve for a regression or classification output by means of a mathematical
      pseudoinverse operation. In the field of neuromorphic engineering, these methods
      are increasingly popular for synthesizing biologically plausible neural networks,
      but the "learning method"-computation of the pseudoinverse by singular value
      decomposition-is problematic both for biological plausibility and because it is
      not an online or an adaptive method. We present an online or incremental method
      of computing the pseudoinverse precisely, which we argue is biologically
      plausible as a learning method, and which can be made adaptable for non
      stationary data streams. The method is significantly more memory-efficient than
      the conventional computation of pseudoinverses by singular value decomposition. 

PMID- 23541927
TI  - The activins and their binding protein, follistatin-Diagnostic and therapeutic
      targets in inflammatory disease and fibrosis.
AB  - The activins, as members of the transforming growth factor-beta superfamily, are
      pleiotrophic regulators of cell development and function, including cells of the
      myeloid and lymphoid lineages. Clinical and animal studies have shown that
      activin levels increase in both acute and chronic inflammation, and are
      frequently indicators of disease severity. Moreover, inhibition of activin action
      can reduce inflammation, damage, fibrosis and morbidity/mortality in various
      disease models. Consequently, activin A and, more recently, activin B are
      emerging as important diagnostic tools and therapeutic targets in inflammatory
      and fibrotic diseases. Activin antagonists such as follistatin, an endogenous
      activin-binding protein, offer considerable promise as therapies in conditions as
      diverse as sepsis, liver fibrosis, acute lung injury, asthma, wound healing and
      ischaemia-reperfusion injury. 

PMID- 23541928
TI  - Osteochondral tissue regeneration using a bilayered composite hydrogel with
      modulating dual growth factor release kinetics in a rabbit model.
AB  - Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels
      have been investigated for the delivery of growth factors (GFs) with the aid of
      gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue
      regeneration. In this study, a bilayered OPF composite hydrogel that mimics the
      distinctive hierarchical structure of native osteochondral tissue was utilized to
      investigate the effect of transforming growth factor-beta3 (TGF-beta3) with
      varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on
      osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect
      model. The four groups investigated included (i) a blank control (no GFs), (ii)
      GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-beta3, and (iv)
      GMP-loaded IGF-1 and GMP-loaded TGF-beta3 in OPF composite hydrogels. The results
      of an in vitro release study demonstrated that TGF-beta3 release kinetics could
      be modulated by the GF incorporation method. At 12weeks post-implantation, the
      quality of tissue repair in both chondral and subchondral layers was analyzed
      based on quantitative histological scoring. All groups incorporating GFs resulted
      in a significant improvement in cartilage morphology compared to the control.
      Single delivery of IGF-1 showed higher scores in subchondral bone morphology as
      well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue
      when compared to a dual delivery of IGF-1 and TGF-beta3, independent of the TGF
      beta3 release kinetics. The results suggest that although the dual delivery of
      TGF-beta3 and IGF-1 may not synergistically enhance the quality of engineered
      tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively
      affects osteochondral tissue repair and holds promise for osteochondral tissue
      engineering applications.

PMID- 23541929
TI  - Impact of flow pulsatility on arterial drug distribution in stent-based therapy.
AB  - Drug-eluting stents reside in a dynamic fluid environment where the extent to
      which drugs are distributed within the arterial wall is critically modulated by
      the blood flowing through the arterial lumen. Yet several factors associated with
      the pulsatile nature of blood flow and their impact on arterial drug deposition
      have not been fully investigated. We employed an integrated framework comprising
      bench-top and computational models to explore the factors governing the time
      varying fluid dynamic environment within the vasculature and their effects on
      arterial drug distribution patterns. A custom-designed bench-top framework
      comprising a model of a single drug-eluting stent strut and a poly-vinyl alcohol
      based hydrogel as a model tissue bed simulated fluid flow and drug transport
      under fully apposed strut settings. Bench-top experiments revealed a relative
      independence between drug distribution and the factors governing pulsatile flow
      and these findings were validated with the in silico model. Interestingly,
      computational models simulating suboptimal deployment settings revealed a complex
      interplay between arterial drug distribution, Womersley number and the extent of
      malapposition. In particular, for a stent strut offset from the wall, total drug
      deposition was sensitive to changes in the pulsatile flow environment, with this
      dependence increasing with greater wall displacement. Our results indicate that
      factors governing pulsatile luminal flow on arterial drug deposition should be
      carefully considered in conjunction with device deployment settings for better
      utilization of drug-eluting stent therapy.

PMID- 23541930
TI  - Single-step grafting of aminooxy-peptides to hyaluronan: a simple approach to
      multifunctional therapeutics for experimental autoimmune encephalomyelitis.
AB  - The immune response to antigens is directed in part by the presence or absence of
      costimulatory signals. The ability to coincidently present both antigen and, for
      example, a peptide that inhibits or activates the costimulatory pathway, would be
      a valuable tool for tolerization or immunization, respectively. A simple reaction
      scheme utilizing oxime chemistry was identified as a means to efficiently
      conjugate different peptide species to hyaluronan. Peptides synthesized with an
      aminooxy N-terminus reacted directly to hyaluronan under slightly acidic aqueous
      conditions without the need for a catalyst. The resulting oxime bond was found to
      rapidly hydrolyze at pH2 releasing peptide, but was stable at higher pH values
      (5.5 and 7). Two different peptide species, a multiple sclerosis antigen (PLP)
      and an ICAM-1 ligand (LABL) known to block immune cell stimulation, were
      functionalized with the aminooxy end group. These peptides showed similar
      reactivity to hyaluronan and were conjugated in an equimolar ratio. The resulting
      hyaluronan with grafted PLP and LABL significantly inhibited disease in mice with
      experimental autoimmune encephalomyelitis, a model of multiple sclerosis.
      Aminooxy-peptides facilitate simple synthesis of multifunctional hyaluronan graft
      polymers, thus enabling novel approaches to antigen-specific immune modulation.

PMID- 23541931
TI  - Evolution of visual field loss over ten years in individuals taking vigabatrin.
AB  - PURPOSE: Vigabatrin-associated visual field loss (VAVFL) occurs in around 45% of
      exposed people. It is generally accepted that, once established, VAVFL is stable
      and does not progress with continued VGB use. Most studies have, however, only
      followed people for short periods. We assessed the evolution of VAVFL over a ten
      year period of continued VGB use. METHODS: From a group of 201 vigabatrin-exposed
      individuals with epilepsy, fourteen individuals were identified who were
      currently taking vigabatrin. All individuals had at least ten years exposure to
      vigabatrin. Individuals underwent several visual field examinations using
      Goldmann perimetry between Test 1 (first recorded examination) and Test 2 (most
      recent examination). All visual field results were analysed and quantified
      retrospectively by one investigator. RESULTS: 174 visual fields from the fourteen
      participants were available. The average follow-up period was 128 months. The
      prevalence of VAVFL increased from 64% at Test 1 to 93% at Test 2. The visual
      field size was significantly smaller at Test 2 compared to Test 1. All subjects
      showed a trend for decreasing visual field size with increasing cumulative
      vigabatrin exposure, when all fields for an individual were taken into account.
      There was a high degree of variability in visual field size between successive
      test sessions. CONCLUSIONS: VAVFL progresses with continued vigabatrin exposure
      over a ten-year period. Progression may be slow and difficult to detect because
      of the high degree of variability in visual field size between successive test
      sessions. New techniques are needed to monitor the effects of vigabatrin
      retinotoxicity in people who continue vigabatrin therapy.

PMID- 23541932
TI  - Fishing and knockout of bioactive compounds using a combination of high-speed
      counter-current chromatography (HSCCC) and preparative HPLC for evaluating the
      holistic efficacy and interaction of the components of Herba Epimedii.
AB  - Due to the complex chemical compositions and pharmacological effects of
      traditional Chinese medicines, we developed a strategy based on fishing and
      knockout of bioactive compounds using a combination of high-speed counter-current
      chromatography (HSCCC) and preparative HPLC for evaluating the holistic activity
      and interaction of the components of Herba Epimedii. First, osteoblast target
      cell extraction was used for preliminary screening of the potential bioactive
      compounds of Herba Epimedii. Second, the bioactive compounds identified (epimedin
      A, epimedin B, epimedin C and icariin) were fished and knocked out using high
      speed counter-current chromatography and preparative HPLC. Third, the bioactivity
      of resulting fractions was assessed by determining their influence on cell
      proliferation and differentiation, thereby allowing for an evaluation of their
      interaction.The pharmacodynamic contribution ratio of each bioactive compound to
      the efficacy of the herbal medicine could then be comprehensively and intuitively
      determined based on the spectra-activity correlations (VIP values) of the tested
      compositions using partial least-squares regression (PLS-R), through which the
      reliability of the screening and isolation of bioactive compounds by the target
      cell extraction technique were verified. The proposed strategy is a useful
      approach with potential application in other traditional Chinese medicines.

PMID- 23541933
TI  - Myocardial lipidomics profiling delineate the toxicity of traditional Chinese
      medicine Aconiti Lateralis radix praeparata.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The lateral root of Aconitum has been popularly
      used in traditional Chinese medicine (TMC) known as Fuzi which is beneficial for
      the treatment of various diseases, such as rheumatism, painful joints, syncope
      and bronchial asthma. However, it has a potential carditoxicity with a relatively
      narrow margin of safety. AIM OF THE STUDY: This paper was designed to explore the
      mechanisms of Fuzi's toxicity and find out potential tissue-specific biomarkers
      of toxic effects. MATERIAL AND METHODS: A myocardial lipidomics based on
      ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass
      spectrometry (UHPLC/Q-TOF MS) was developed to compare three cardiac lipid
      extraction methods and investigate the changes of lipids in mice heart of three
      different dosage groups. In addition, we concurrently inspected the biochemical
      parameters in plasma, observed the histology of the heart and recorded the
      electrocardiogram (ECG). RESULTS: The cardiotoxicity of Fuzi was dose-dependent,
      and the high-dose group obviously manifested the heart damage in histology and a
      certain degree of arrhythmia. Significant changes of 14 lipid metabolites which
      primarily involved in phospholipid metabolism, sphingolipid metabolism, saturated
      fatty acid oxidation and unsaturated fatty acid peroxidation were identified and
      considered as the potential biomarkers of Fuzi toxicity. CONCLUSION: The
      lipidomics approach is helpful to search potential tissue-specific biomarkers and
      understand the underlying mechanisms of Fuzi toxicity on the heart.

PMID- 23541934
TI  - Vasorelaxant effects and mechanisms of action of Heracleum sphondylium L.
      (Apiaceae) in rat thoracic aorta.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Heracleum sphondylium L. (HS) are
      used in traditional medicine to treat hypertension. To provide pharmacological
      basis for this use, we investigated the vasorelaxant effects of a dichloromethane
      extract of HS (HSDE) and the mechanisms involved. MATERIALS AND METHODS: Activity
      of HSDE was evaluated on rat isolated thoracic aortic rings. RESULTS: HSDE
      induced vasorelaxation in phenylephrine (PE, 10(-6)mol/L) and high KCl-(6*10(
      2)mol/L) pre-contracted aortic rings that was independent on the presence of
      endothelium. HSDE markedly decreased extracellular Ca(2+)-induced contraction in
      high-KCl and PE pre-challenged rings. It also inhibited the intracellular Ca(2+)
      release sensitive to PE (10(-6)M). The relaxant effect of HSDE were blunted by 4
      amino-pyridine (4-AP, 10(-3)mol/L), an inhibitor of voltage-dependent K(+)
      channels. CONCLUSION: Our results provide the first evidence that a
      dichloromethane extract of Heracleum sphondylium L. exhibits vasorelaxant
      properties through endothelium-independent mechanisms involving the inhibition of
      Ca(2+) mobilization and changes in Kv channel conductances. These data argue for
      its use as antihypertensive therapy in traditional medicine.

PMID- 23541935
TI  - Spiritual and ceremonial plants in North America: an assessment of Moerman's
      ethnobotanical database comparing Residual, Binomial, Bayesian and Imprecise
      Dirichlet Model (IDM) analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical research and the study of plants
      used for rituals, ceremonies and to connect with the spirit world have led to the
      discovery of many novel psychoactive compounds such as nicotine, caffeine, and
      cocaine. In North America, spiritual and ceremonial uses of plants are well
      documented and can be accessed online via the University of Michigan's Native
      American Ethnobotany Database. AIM OF THE STUDY: The objective of the study was
      to compare Residual, Bayesian, Binomial and Imprecise Dirichlet Model (IDM)
      analyses of ritual, ceremonial and spiritual plants in Moerman's ethnobotanical
      database and to identify genera that may be good candidates for the discovery of
      novel psychoactive compounds. MATERIALS AND METHODS: The database was queried
      with the following format "Family Name AND Ceremonial OR Spiritual" for 263 North
      American botanical families. Spiritual and ceremonial flora consisted of 86
      families with 517 species belonging to 292 genera. Spiritual taxa were then
      grouped further into ceremonial medicines and items categories. Residual,
      Bayesian, Binomial and IDM analysis were performed to identify over and under
      utilized families. RESULTS: The 4 statistical approaches were in good agreement
      when identifying under-utilized families but large families (>393 species) were
      underemphasized by Binomial, Bayesian and IDM approaches for over-utilization.
      Residual, Binomial, and IDM analysis identified similar families as over-utilized
      in the medium (92-392 species) and small (<92 species) classes. The families
      Apiaceae, Asteraceae, Ericacea, Pinaceae and Salicaceae were identified as
      significantly over-utilized as ceremonial medicines in medium and large sized
      families. Analysis of genera within the Apiaceae and Asteraceae suggest that the
      genus Ligusticum and Artemisia are good candidates for facilitating the discovery
      of novel psychoactive compounds. CONCLUSIONS: The 4 statistical approaches were
      not consistent in the selection of over-utilization of flora. Residual analysis
      revealed overall trends that were supported by Binomial analysis when separated
      into small, medium and large families. The Bayesian, Binomial and IDM approaches
      identified different genera as potentially important. Species belonging to the
      genus Artemisia and Ligusticum were most consistently identified and may be
      valuable in future studies of the ethnopharmacology.

PMID- 23541936
TI  - Use of archived biopsy specimens to study gene expression in oral mucosa from
      chemotherapy-treated cancer patients.
AB  - OBJECTIVES: Oral mucositis caused by cancer chemotherapy can result in
      significant clinical complications. There is a strategic need to accelerate the
      delineation of the pathobiology. This proof-of-principle study was designed to
      demonstrate the feasibility of studying archived oral mucosal specimens to
      further delineate oral mucositis pathobiology. MATERIALS AND METHODS: Twenty-nine
      formalin-fixed and paraffin-embedded tissue blocks of 25-year-old oral mucosa
      autopsy specimens from cancer chemotherapy patients were studied. Standardized
      technology was utilized, including RNA isolation and amplification, array
      hybridization, and gene expression analysis. RESULTS: A predominance of DNA
      damage in buccal mucosal basal keratinocytes was observed. Data comparing basal
      cells from buccal vs. gingival mucosa identified differential gene expression of
      host responses in relation to pathways relevant to oral mucositis pathogenesis,
      including responses to cancer-associated inflammation. CONCLUSIONS: This proof-of
      principle study demonstrated that archived oral mucosal specimens may be a
      potentially valuable resource for the study of oral mucositis in cancer patients.

PMID- 23541937
TI  - Oncological outcome and prognostic factors in malignant parotid tumours.
AB  - OBJECTIVE: To evaluate the oncological outcome of malignant parotid tumours and
      identify the prognostic factors for survival. STUDY DESIGN: Retrospective study.
      METHODS: One hundred and forty-one patients with primary epithelial carcinoma of
      the parotid gland were examined. The overall survival (OS) and disease specific
      survival (DSS) rates were calculated. The DSS was evaluated according to
      different parameters. RESULTS: The 5- and 10-year OS rates were 72.3% and 58.4%.
      The 5- and 10-year DSS rate was 75% and 71%, respectively. The univariate
      analysis showed that the pathological staging, clinical and pathological tumour
      and nodal status, surgical procedure and histological subtype significantly
      influenced the DSS (P <= 0.05). The 5- and 10-year loco-regional control rates
      were 82.1% and 78%. The multivariate analysis showed that the pathological nodal
      status and the pathological staging influenced the DSS. It further demonstrated
      that the clinical tumour status and the histological subtype were the most
      important preoperative prognostic factors. CONCLUSION: The pathological nodal
      status, the pathological staging, the clinical tumour status and the histological
      subtype are the most important factors influencing survival in malignant parotid
      tumours.

PMID- 23541938
TI  - Effects of growth on maxillary distraction osteogenesis in cleft lip and palate.
AB  - PURPOSE: The objective was to analyze the effects of growth on the long-term
      result of maxillary distraction osteogenesis (DO) in cleft lip and palate (CLP).
      PATIENTS AND METHODS: Retrospective study of 24 CLP cases with long-term follow
      up operated for maxillary DO using the Polley and Figueroa technique: 10 patients
      were distracted during growth, while 14 patients were operated after their growth
      spurt. Preoperative (T0), 6-12 months postoperative (T1), and >=4 years
      postoperative (T2) cephalometric radiographs were evaluated. A classical
      cephalometric analysis was used to assess the treatment stability, and a
      Procrustes superimposition method was performed to assess local changes in the
      maxilla and the mandible. RESULTS: At T0, the mean age was of 11.9 +/- 1.4 years
      for growing patient, and 17.9 +/- 3.5 years for patient treated after their
      growth spurt (P < 0.001). Between T0 and T1, a greater increase of the SNA was
      shown in growing patients (P = 0.036), but the relapse was more important between
      T1 and T2, with a significant decrease of the SNA (P = 0.002) and ANB (P = 0.032)
      compared to the patients treated after their growth spurt. Although not
      significant, growing patients showed greater rotations of their palatal plane and
      mandibular plane. CONCLUSIONS: Maxillary DO in CLP does not correct the growth
      deficit inherent to the pathology. Overcorrection of at least 20% is advised
      during growth.

PMID- 23541939
TI  - The Safe Clinical Assessment: a patient safety focused approach to clinical
      assessment.
AB  - Medical consultations are complex and multi-faceted, requiring that nurses
      develop a sound knowledge and skill base in a wide variety of different areas,
      from communication skills to clinical reasoning and from physical assessment
      skills to prescription writing. Clinical assessment is an integral part of the
      medical consultation process, although it is often taught as a stand-alone module
      in nurse education programmes, such that nurses at different levels in their
      training will learn these skills. This article describes how patient safety
      skills and practices can be incorporated into clinical assessment teaching for
      nurses at all levels of training but especially within training programmes for
      Emergency Nurse Practitioners, Nurse Practitioners and for nurses involved in the
      assessment and management of patients with minor illnesses. 

PMID- 23541940
TI  - TNIP1/ANXA6 and CSMD1 variants interacting with cigarette smoking, alcohol intake
      affect risk of psoriasis.
AB  - BACKGROUND: Psoriasis is a common multi-factorial skin disease, in which gene
      gene and gene-environment interactions may affect the onset, manifestation and
      clinical course. OBJECTIVE: To investigate the underlying gene-environment
      interaction among several established susceptibility genes, cigarette smoking and
      alcohol intake. METHODS: Using a two-stage case-control design, we searched for
      pairwise interactions between cigarette smoking and alcohol intake respectively
      with 9 single nucleotide polymorphisms (SNPs) at ERAP1, PTTG1, CSMD1, GJB2,
      SERPINB8, ZNF816A and TNIP1/ANXA6 that have been associated with risk for
      psoriasis in 7,223 subjects. Multiple logistic regression analysis was used for
      data analysis. RESULTS: Significant interactions were found for alcohol intake
      with rs3762999 (p=0.0257) and rs999556 (p=0.0071) at TNIP/ANXA6; and for
      cigarette smoking with rs7007032 (p=0.0023) and rs10088247 (p=0.0023) at CSMD1.
      CONCLUSION: This study provides empirical evidence for the gene-environment
      interactions between TNIP1/ANXA6 and alcohol use, CSMD1 and cigarette smoking,
      highlighting the importance of gene-environment interactions in the pathogenesis
      of psoriasis.

PMID- 23541941
TI  - Characterization, mapping, and mitigation of mercury vapour emissions from
      artisanal mining gold shops.
AB  - Artisanal miners sell their gold to shops that are usually located in the urban
      core, where the mercury-gold amalgam is burned to evaporate the mercury that was
      added during ore processing. People living and working near these gold shops are
      exposed to intermittent and extreme concentrations of mercury vapour. In the
      urban centres of Segovia, Colombia, and Andacollo, Chile, the average
      concentrations measured by mobile mercury vapour analyzer transects taken
      repeatedly over several weeks were 1.26 and 0.338MUgm(-3), respectively. By World
      Health Organization standards, these towns are exposed to significant health
      hazard, and globally, the millions of miners, as well as non-miners who live near
      gold shops, are at serious risk of neurological and renal deficits. Measurements
      taken in Suriname, Ecuador and Peru reveal this to be a widespread phenomenon
      with unique regional variations and myriad attempts at remediation. Maps of
      average mercury concentrations show the spatial distribution of the hazard in
      relation to residential buildings and schools. Measurements from towers show the
      temporal variability of mercury concentrations, and suggest that large quantities
      of mercury are available for long-range atmospheric transport. Mercury mapping in
      Segovia in 2011 suggest a 10% reduction in airborne mercury concentrations over
      2010, despite a 30% increase in gold production. This is attributable to the
      adoption of retorts by miners and regulations banning new processing centres to
      the rural periphery. This is the first full description of artisanal mining gold
      shop practices and of the character, quantity, and remediation of mercury
      emissions within urban mining centres. 

PMID- 23541942
TI  - Regulation of N-Myc downstream regulated gene 2 by bile acids.
AB  - Here we report that bile acid chenodeoxycholic acid (CDCA) and synthetic
      farnesoid X receptor (FXR) agonist GW4064 robustly induced tumor suppressor N-Myc
      downstream regulated gene 2 (NDRG2) expression in human hepatoma cells and
      primary hepatocytes. Knockdown of FXR abolished the induction by CDCA, whereas
      overexpression of a constitutively active form of FXR increased NDRG2 expression.
      A FXR-response element was identified within intronic regions of human and murine
      genes. Moreover, mice given GW4064 exhibit an increase of Ndrg2 expression in
      liver and kidney, where both NDRG2 and FXR are enriched. The identification of
      NDRG2 as a bile acid regulated gene may provide novel knowledge toward the
      understanding of NDRG2 physiological function and the link between metabolism and
      cancer.

PMID- 23541943
TI  - Identification of small molecules that promote human embryonic stem cell self
      renewal.
AB  - Human embryonic stem cells (hESCs) and induced pluripotent cells have the
      potential to provide an unlimited source of tissues for regenerative medicine.
      For this purpose, development of defined/xeno-free culture systems under feeder
      free conditions is essential for the expansion of hESCs. Most defined/xeno-free
      media for the culture of hESCs contain basic fibroblast growth factor (bFGF).
      Therefore, bFGF is thought to have an almost essential role for the expansion of
      hESCs in an undifferentiated state. Here, we report identification of small
      molecules, some of which were neurotransmitter antagonists (trimipramine and
      ethopropazine), which promote long-term hESC self-renewal without bFGF in the
      medium. The hESCs maintained high expression levels of pluripotency markers, had
      a normal karyotype after 20 passages, and could differentiate into all three germ
      layers.

PMID- 23541944
TI  - Transcriptional characterization of Wnt pathway during sequential hepatic
      differentiation of human embryonic stem cells and adipose tissue-derived stem
      cells.
AB  - Human embryonic stem cells (hESs) and adipose-derived stem cells (hADSCs) are
      able to differentiate into hepatocytes. However, a role of Wnt signaling in
      hepatic differentiation of stem cells is unclear. This study characterized the
      transcriptional expression pattern of Wnt signaling genes during the sequential
      hepatocytes differentiation of hES and hADSC. The sequential hepatocytes
      differentiation of hES and hADSC was induced by three steps including induction,
      differentiation and maturation steps with the treatment of cytokines. Hepatocytes
      differentiation was more efficient in hES than hADSC in terms of the expression
      of hepatocyte-specific genes and the cellular uptake of ICG. The expression of
      WNT2B, WNT5A, and WISP1 increased at late hepatic differentiation of hES, but the
      expression of DKK1 and CCND1 decreased during early hepatic differentiation of
      hES. During hepatic differentiation of hADSC, the expression of WNT2B and WISP1
      decreased, but the expression of WNT5B and DKK1 increased at late hepatic
      differentiation. These results showed that Wnt signaling appears to be activated
      in hepatic differentiation of hES, but repressed in hepatic differentiation of
      hADSC in a time-dependent manner, which suggests the differential regulation of
      Wnt signaling for hepatic differentiation of hES and hADSC.

PMID- 23541945
TI  - MiR-29a modulates the angiogenic properties of human endothelial cells.
AB  - Although extensive investigation has been made on miR-29a in relation to
      malignancies, only a little information has been provided about the angiogenic
      property of this miRNA so far. Herein, we sought to investigate the role of miR
      29a in regulating cell cycle and angiogenic phenotype of endothelial cells. The
      results showed that miR-29a is highly expressed and upregulated by hypoxia
      mimicking reagents in human umbilical vein endothelial cells (HUVEC). Consistent
      with this preliminary finding, introduction of exogenous agomiR-29a, or Antagomir
      29a altered cell cycle progression and promoted, or repressed the proliferation
      and tube formation of HUVEC, respectively. Furthermore, by using luciferase
      reporter assay, the expression of HBP1, a suppressor transcription factor was
      directly regulated by miR-29a through 3'-UTR. Increased or decreased HBP1 protein
      level was associated with the inhibition or overexpression of miR-29a,
      respectively. We conclude that miR-29a has a significant role in regulating cell
      cycle, proliferation and angiogenic properties of HUVEC, and this function is
      likely mediated through HBP1 protein at the post-transcriptional level. As a
      novel molecular target, miR-29a may have a potential value for the treatment of
      angiogenesis-associated diseases such as cardiovascular diseases and cancers.

PMID- 23541946
TI  - Chidamide, a novel histone deacetylase inhibitor, synergistically enhances
      gemcitabine cytotoxicity in pancreatic cancer cells.
AB  - Pancreatic cancer is a lethal human malignancy with an extremely poor prognosis
      and urgently requires new therapies. Histone deacetylase inhibitors (HDACIs)
      represent a new class of anticancer agents and have shown promising antitumor
      activities in preclinical models of pancreatic cancer. In this study, we sought
      to determine the antitumor effects of a novel HDACI, chidamide (CS055), in
      pancreatic cancer cells alone or in combination with gemcitabine. Treatments of
      BxPC-3 or PANC-1 pancreatic cancer cell lines with chidamide resulted in dose-
      and time-dependent growth arrest, accompanied by induction of p21 expression.
      When combined in a sequential schedule, chidamide synergistically enhanced
      gemcitabine-induced cell growth arrest and apoptosis, accompanied by cooperative
      downregulation of Mcl-1 and loss of mitochondrial membrane potential (DeltaPsim).
      Chidamide enhanced gemcitabine-induced DNA double-strand breaks and S phase
      arrest, and abrogated the G2/M cell cycle checkpoint, potentially through
      suppression of CHK1 expression. Our results suggest that chidamide has a
      therapeutic potential for treating pancreatic cancer, especially in combination
      with gemcitabine.

PMID- 23541947
TI  - Nutraceuticals as new treatment approaches for oral cancer: II. Green tea
      extracts and resveratrol.
AB  - Nutraceuticals with anti-neoplastic potential are suitable candidates for
      extending the range of therapeutic options for several types of cancers. One of
      these malignancies is oral cancer of the squamous cell carcinoma type, for which
      current treatment approaches have not succeeded in improving long-term clinical
      outcome. We recently reviewed the beneficial effects of curcumin for the
      treatment of oral cancer. In the current review, we focused on the beneficial
      effects of other two nutraceuticals, green tea extracts [especially (-)
      epigallocatechin-3-gallate (EGCG)] and resveratrol, in the treatment of oral
      cancer. In vivo and in vitro studies as well as clinical trials were reviewed,
      focusing on the beneficial effect of each of these plant-derived dietary agents,
      either alone or in combination with various pharmacological agents. We also
      presented the anti-cancer effects against cancer cells and against components of
      the tumor microenvironment. It emerged that the poor bioavailability of these
      nutraceuticals poses an obstacle to their exerting adequate anti-cancer
      potential. Ground-breaking studies employing new nanotechnology-based therapeutic
      approaches were presented.

PMID- 23541948
TI  - Signaling pathways mediating the effects of insulin-like growth factor-I in
      bovine muscle satellite cells.
AB  - The objective of this study was to identify the signaling pathways mediating the
      effects of IGF-I on muscle cell proliferation, protein synthesis, and protein
      degradation in a physiologically more relevant muscle cell model. We isolated
      muscle satellite cells from adult cattle and expanded them as myoblasts or
      induced them to form myotubes in culture. We determined the effects of IGF-I on
      proliferation of myoblasts and protein synthesis and degradation in myotubes in
      the presence or absence of specific signaling inhibitors. Our data suggest that
      both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on
      myoblast proliferation and that the PI3K/AKT pathway mediates this effect through
      cyclin D2. Our data also suggest that both the MEK/ERK and PI3K/AKT pathways
      mediate the stimulatory effect of IGF-I on protein synthesis through p70S6K and
      that the PI3K/AKT pathway mediates the inhibitory effect of IGF-I on protein
      degradation through FoxO3a.

PMID- 23541949
TI  - The effects of RFRP-3, the mammalian ortholog of GnIH, on the female pig
      reproductive axis in vitro.
AB  - RFamide-related peptide-3 (RFRP-3) has been proposed as a key inhibitory
      regulator of mammalian reproduction. To further determine the potential
      mechanisms and sites of action of RFRP-3, we systematically investigated the
      direct effect of RFRP-3 on the female pig reproductive axis in vitro. Initially,
      we confirmed that G protein-coupled receptor 147 (GPR147) was distributed in
      isolated hypothalamic, anterior pituitary and ovarian granulosa cells, suggesting
      that RFRP-3 could act on these cells in vitro. Subsequently, the direct effects
      of RFRP-3 on hormone and steroid secretion, the synthesis of subunit genes and
      the expression of proteins related to proliferation in the hypothalamus,
      pituitary and ovary were evaluated. Our results demonstrate that different doses
      of RFRP-3 inhibited the release and synthesis of gonadotrophin releasing hormone,
      gonadotrophin and steroid hormones and impacted the relative gene expression of
      KISS1 and GnRHR and the protein expression of cyclin B1, PCNA and ERK 1/2.

PMID- 23541950
TI  - Genome-wide association studies on serum sex steroid levels.
AB  - Even though the levels of circulating sex steroid hormones are to a large extent
      heritable, their genetic determinants are largely unknown. With the advent of
      genome-wide association studies (GWAS), much progress has been made and several
      genetic loci have been identified to be associated with serum levels of
      dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin.
      The variants identified so far only explain a small amount of the overall
      heritability, but may help to elucidate the role of sex steroid hormones in
      common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive
      cancers. This review provides an overview of the current state of knowledge of
      the genetic determinants of sex steroid hormones, with a focus on recent GWAS and
      brief directions for elucidating the remaining heritability. 

PMID- 23541951
TI  - STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.
AB  - The mammary gland is a unique organ that undergoes extensive and profound changes
      during puberty, menstruation, pregnancy, lactation and involution. The changes
      that take place during puberty involve large-scale proliferation and invasion of
      the fat-pad. During pregnancy and lactation, the mammary cells are exposed to
      signaling pathways that inhibit apoptosis, induce proliferation and invoke
      terminal differentiation. Finally, during involution the mammary gland is exposed
      to milk stasis, programmed cell death and stromal reorganization to clear the
      differentiated milk-producing cells. Not surprisingly, the signaling pathways
      responsible for bringing about these changes in breast cells are often subverted
      during the process of tumorigenesis. The STAT family of proteins is involved in
      every stage of mammary gland development, and is also frequently implicated in
      breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland
      development and tumorigenesis are well studied, others members, e.g. STAT1 and
      STAT6, have only recently been observed to play a role in mammary gland biology.
      Continued investigation into the STAT protein network in the mammary gland will
      likely yield new biomarkers and risk factors for breast cancer, and may also lead
      to novel prophylactic or therapeutic strategies against breast cancer. 

PMID- 23541952
TI  - Control of autophagic cell death by caspase-10 in multiple myeloma.
AB  - We performed a loss-of-function RNA interference screen to define therapeutic
      targets in multiple myeloma, a genetically diverse plasma cell malignancy.
      Unexpectedly, we discovered that all myeloma lines require caspase-10 for
      survival irrespective of their genetic abnormalities. The transcription factor
      IRF4 induces both caspase-10 and its associated protein cFLIPL in myeloma,
      generating a protease that does not induce apoptosis but rather blocks an
      autophagy-dependent cell death pathway. Caspase-10 inhibits autophagy by cleaving
      the BCL2-interacting protein BCLAF1, itself a strong inducer of autophagy that
      acts by displacing beclin-1 from BCL2. While myeloma cells require a basal level
      of autophagy for survival, caspase-10 tempers this response to avoid cell death.
      Drugs that disrupt this vital balance may have therapeutic potential in myeloma.

PMID- 23541954
TI  - A novel direct contact method for the assessment of the antimicrobial activity of
      dental cements.
AB  - Dental cements are a crucial part of the odontological treatment, however, due to
      the hazardous nature and reduced biological efficiency of some of the used
      materials, newer and safer alternatives are needed, particularly so those
      possessing higher antimicrobial activity than their traditional counterparts. The
      evaluation of the antimicrobial properties of solid and semi-solid
      antimicrobials, such as dental cements and gels, is challenging, particularly due
      to the low sensitivity of the current methods. Thus, the main aim of this study
      was the evaluation of the antimicrobial activity of a novel chitosan containing
      dental cement while simultaneous assessing/validating a new, more efficient,
      method for the evaluation of the antimicrobial activity of solid and gel like
      materials. The results obtained showed that the proposed method exhibited a
      higher sensitivity than the standard 96 well microtiter assay and allowed the
      determination of bactericidal activity. Additionally, it is interesting to note
      that the chitosan containing cement, which presented higher antimicrobial
      activity than the traditional zinc oxide/eugenol mix, was capable of inducing a
      viable count reduction above 5 log of CFU for all of the studied microorganisms.

PMID- 23541953
TI  - Caveolin-3 suppresses late sodium current by inhibiting nNOS-dependent S
      nitrosylation of SCN5A.
AB  - AIMS: Mutations in CAV3-encoding caveolin-3 (Cav3) have been implicated in type 9
      long QT syndrome (LQT9) and sudden infant death syndrome (SIDS). When co
      expressed with SCN5A-encoded cardiac sodium channels these mutations increased
      late sodium current (INa) but the mechanism was unclear. The present study was
      designed to address the mechanism by which the LQT9-causing mutant Cav3-F97C
      affects the function of caveolar SCN5A. METHODS AND RESULTS: HEK-293 cells
      expressing SCN5A and LQT9 mutation Cav3-F97C resulted in a 2-fold increase in
      late INa compared to Cav3-WT. This increase was reversed by the neural nitric
      oxide synthase (nNOS) inhibitor L-NMMA. Based on these findings, we hypothesized
      that an nNOS complex mediated the effect of Cav3 on SCN5A. A SCN5A macromolecular
      complex was established in HEK-293 cells by transiently expressing SCN5A, alpha1
      syntrophin (SNTA1), nNOS, and Cav3. Compared with Cav3-WT, Cav3-F97C produced
      significantly larger peak INa amplitudes, and showed 3.3-fold increase in the
      late INa associated with increased S-nitrosylation of SCN5A. L-NMMA reversed both
      the Cav3-F97C induced increase in late and peak INa and decreased S-nitrosylation
      of SCN5A. Overexpression of Cav3-F97C in adult rat cardiomyocytes caused a
      significant increase in late INa compared to Cav3-WT, and prolonged the action
      potential duration (APD90) in a nNOS-dependent manner. CONCLUSIONS: Cav3 is
      identified as an important negative regulator for cardiac late INa via nNOS
      dependent direct S-nitrosylation of SCN5A. This provides a molecular mechanism
      for how Cav3 mutations increase late INa to cause LQT9. This article is part of a
      Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".

PMID- 23541955
TI  - Optimization of Matrix-Assisted-Laser-Desorption-Ionization-Time-Of-Flight Mass
      Spectrometry for the identification of bacterial contaminants in beverages.
AB  - The growth of microbial contaminants in industrially produced beverages can cause
      turbidity, haze and off-flavors resulting in quality loss often rendering the
      product undrinkable. In this work Matrix-Assisted-Laser-Desorption-Ionization
      Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) based on the generation of
      peptide mass fingerprints, which form a distinctive protein peak pattern, is
      presented as a rapid, reliable and powerful tool for the identification of
      spoilage bacteria encountered in beverages. Lactobacillus brevis, Pediococcus
      claussenii and Leuconostoc mesenteroides were used to optimize sample preparation
      and MALDI-TOF MS-settings. Different sample preparation methods ranging from
      plain cell smears to more elaborate extraction procedures including mechanical
      and enzymatical disruption of cells were investigated. The effects of culturing
      time and the availability of oxygen and nutrients on the acquired protein peak
      patterns were studied. While cell smears at times hampered the acquisition of
      spectra for strain L. brevis all other procedures constantly delivered good
      quality spectra for all three strains. The extraction procedure allowed good
      reproducibility of spectra with high information content and enabled
      differentiation on the species level regardless of the culture conditions used.
      The application of specific culture conditions to microorganisms resulted in
      minor but stable changes in spectra, which were not sufficient to impair
      identification of isolates on the species level.

PMID- 23541956
TI  - Slowing PCR ramp speed reduces chimera formation from environmental samples.
AB  - Chimeric sequences falsely increase the apparent diversity within samples. To
      examine chimera formation in PCR products from environmental DNA, clone libraries
      were prepared using different ramp speeds to reach the designated temperatures
      for each step of the PCR program. Slowing the thermocycler ramp speed to 1 
      degrees C s(-1) reduced chimera formation.

PMID- 23541957
TI  - The Short Form 36 English and Chinese versions were equivalent in a multiethnic
      Asian population.
AB  - OBJECTIVE: The primary aim of this article was to evaluate measurement
      equivalence of the English and Chinese versions of the Short Form 36 version 2
      (SF-36v2) and Short Form 6D (SF-6D). STUDY DESIGN AND SETTING: In this cross
      sectional study, health-related quality of life (HRQoL) was measured from 4,973
      ethnic Chinese subjects using the SF-36v2 questionnaire. Measurement equivalence
      of domain and utility scores for the English- and Chinese-language SF-36v2 and SF
      6D were assessed by examining the score differences between the two languages
      using linear regression models, with and without adjustment for known
      determinants of HRQoL. Equivalence was achieved if the 90% confidence interval
      (CI) of the differences in scores, due to language, fell within a predefined
      equivalence margin. RESULTS: Compared with English-speaking Chinese, Chinese
      speaking Chinese were significantly older (47.6 vs. 55.5 years). All SF-36v2
      domains were equivalent after adjusting for known HRQoL. SF-6D utility/items had
      the 90% CI either fully or partially overlap their predefined equivalence margin.
      CONCLUSION: The English- and Chinese-language versions of the SF-36v2 and SF-6D
      demonstrated equivalence.

PMID- 23541958
TI  - British English translation of the Food Craving Inventory (FCI-UK).
AB  - There is evidence for cultural variation in the foods that may be craved. We have
      designed and tested, in a sample of 234 participants, a UK-specific version of
      the Food Craving Inventory. A four-factor structure comprising of sweet foods,
      fast foods, high fat, and complex carbohydrates was extracted. The final scale
      was analogous with the original US scale, and shared similar associations with
      external eating and dietary restraint, although no association was found with
      BMI. The measure has potential to contribute to the development of theoretical
      understanding of food craving, and to measuring outcomes in intervention studies
      and clinical samples.

PMID- 23541959
TI  - The otological manifestations associated with autistic spectrum disorders.
AB  - OBJECTIVES: To elucidate the otological manifestations found in this increasingly
      commonly diagnosed condition. This paper will discuss the diagnosis, aetiology,
      pathogenesis, management and the outcomes of treatment. STUDY DESIGN: Systematic
      literature review. MATERIALS AND METHODS: The following databases were searched
      for articles pertaining to the otological manifestations of autistic spectrum
      disorders: MEDLINE, EMBASE, CURRENT CONTENTS, PSYCHLIT, CINAHL and HEALTHSTAR.
      Articles from 1965 to June 2012 were extracted. Relevant articles from the
      literature were selected and reviewed by two independent authors. Each paper was
      assessed as to its level of evidence and validity. The relevant results are
      presented and discussed in order to present a practical approach to the
      management of these patients. RESULTS: Patients with ASD have an increased
      incidence of peripheral and central otological pathology. This pathology plays a
      key role in the behavioural, communication, and social aspects of the disease.
      ASD patients have a higher incidence of profound sensorineural hearing loss,
      middle ear infections, and abnormalities of the cochlear nerve and brainstem
      auditory pathways. There are cortical and brainstem neurodevelopmental
      abnormalities in the way auditory information is interpreted and processed in the
      ASD patient. CONCLUSIONS: The otolaryngologist plays a key role in the
      multidisciplinary management of individuals with ASD due to the high prevalence
      of otological pathology amongst these patients. Early diagnosis and expedient
      treatment focusing on normalisation of auditory input and development can
      maximise developmental outcomes.

PMID- 23541960
TI  - Some studies on evaluation of degradation in composite adhesive joints using
      ultrasonic techniques.
AB  - Experimental and theoretical studies on degradation of composite-epoxy adhesive
      joints were carried out on samples having different interfacial and cohesive
      properties. Oblique incidence ultrasonic inspection of bonded joints revealed
      that degradation in the adhesive can be measured by significant variation in
      reflection amplitude as also by a shift in the minima of reflection spectrum. It
      was observed that severe degradation of the adhesive leads to failure dominated
      by interfacial mode. Through this investigation it is demonstrated that a
      correlation exists between the bond strength and a frequency shift in reflection
      minimum. The experimental data was validated using analytical models. Though both
      bulk adhesive degradation and interfacial degradation influences the shift in
      spectrum minimum, the contribution of the latter was found to be significant. An
      inversion algorithm was used to determine the interfacial transverse stiffness
      using the experimental oblique reflection spectrum. The spectrum shift was found
      to depend on the value of interfacial transverse stiffness using which a
      qualitative assessment can be made on the integrity of the joint.

PMID- 23541961
TI  - The impact of micromachined ultrasonic radiators on the efficiency of transducers
      in air.
AB  - The use of micromachined thin-film ultrasonic radiators to improve the efficiency
      of conventional in-air acoustic transducers is investigated. We conduct a
      theoretical investigation of the parameters that determine the efficiency of thin
      film transducers, using a lumped parameter model, and show that the efficiency
      can be improved by choosing a radiating plate thickness that can be realized by
      micromachining. We also identified the problems that should be overcome to design
      and fabricate a micromachined ultrasonic transducer with the theoretically
      predicted efficiency. Based on the lumped parameter model, we showed that the
      problems can be resolved via an appropriate design scheme. A piezoelectric
      micromachined ultrasonic transducer is designed and fabricated to demonstrate the
      impact of the proposed design method. Test results for the fabricated radiator
      indicated that it provided an electroacoustic efficiency of 58.4%, up to 300%
      greater than either the unit previously fabricated by the authors or conventional
      unimorph ultrasonic transducers. An array of the proposed transducers was also
      designed, fabricated, and tested as a source transducer for a parametric array,
      since transducer efficiency is important for practical applications of a
      parametric array. The test results for the proposed transducer demonstrate its
      potential for improving the practicality of parametric array sources, such as
      parametric loudspeakers and directional ultrasonic ranging sensors.

PMID- 23541962
TI  - Application of in situ thermography for evaluating the high-cycle and very high
      cycle fatigue behaviour of cast aluminium alloy AlSi7Mg (T6).
AB  - The present paper illustrates the application of infrared thermal measurements
      for the investigation of crack initiation point and crack propagation in the high
      cycle and the very high-cycle fatigue range of cast AlSi7Mg alloy (A356). The
      influence of casting defects, their location, size and amount was studied both by
      fractography and thermography. Besides internal and surface fatigue crack
      initiation as a further crack initiation type multiple fatigue crack initiation
      was observed via in situ thermography which can be well correlated with the
      results from fractography obtained by SEM investigations. In addition, crack
      propagation was studied by the development of the temperature measured via
      thermography. Moreover, the frequency influence on high-cycle fatigue behaviour
      was investigated. The presented results demonstrate well that the combination of
      fractography and thermography can give a significant contribution to the
      knowledge of crack initiation and propagation in the VHCF regime. 

PMID- 23541963
TI  - Is electricity useful when the pump is failing?: more data urgently needed.

PMID- 23541964
TI  - Noninvasive renal sympathetic denervation by extracorporeal high-intensity
      focused ultrasound in a pre-clinical canine model.
AB  - OBJECTIVES: This study investigated the feasibility of noninvasive renal
      sympathetic denervation (RSD) by using the novel approach of extracorporeal high
      intensity focused ultrasound (HIFU). BACKGROUND: Catheter-based RSD has achieved
      promising clinical outcomes. METHODS: Under the guidance of Doppler flow imaging,
      therapeutic ablations (250 W * 2 s) were performed by using extracorporeal HIFU
      on the bilateral renal nerves (36.3 +/- 2.8 HIFU emissions in each animal) in a
      mean 27.4-min procedure in 18 healthy canines of the ablation group. Similar
      procedures without acoustic energy treatment were conducted in 5 canines of the
      sham group. The animals were killed on day 6 or 28. Blood pressure (BP), plasma
      noradrenaline (NA) level, and renal function were determined on days 0, 6, and
      28. Pathological examinations were performed on all retrieved samples. RESULTS:
      All of the animals survived the treatment. After ablation, BP and NA
      significantly decreased compared with the baseline values (BP changed -15.9/-13.6
      mmHg, NA changed -55.4% [p < 0.001] 28 days after ablation]) and compared with
      the sham group on days 6 and 28. Ablation lesions around the renal artery
      adventitia were observed on day 6. A histological examination revealed the
      disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent
      denervation on day 28. No procedure-related complications were observed.
      CONCLUSIONS: Effective RSD was successfully achieved by using the extracorporeal
      HIFU method in canines. Thus, noninvasive HIFU may be further explored as an
      important and novel strategy for RSD.

PMID- 23541966
TI  - Reply: To PMID 23265334.

PMID- 23541965
TI  - Oxidation-specific biomarkers and risk of peripheral artery disease.
AB  - OBJECTIVES: The goal of this study was to examine the prospective association
      between oxidation-specific biomarkers, primarily oxidized phospholipids (OxPL) on
      apolipoprotein B-100-containing lipoproteins (OxPL/apoB) and lipoprotein (a)
      [Lp(a)], and risk of peripheral artery disease (PAD). We examined, as secondary
      analyses, indirect measures of oxidized lipoproteins, including autoantibodies to
      malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B
      100 immune complexes (ApoB-IC). BACKGROUND: Biomarkers to predict the development
      of PAD are lacking. OxPL circulate in plasma, are transported by Lp(a), and
      deposit in the vascular wall and induce local inflammation. METHODS: The study
      population included 2 parallel nested case-control studies of 143 men within the
      Health Professionals Follow-up Study (1994 to 2008) and 144 women within the
      Nurses' Health Study (1990 to 2010) with incident confirmed cases of clinically
      significant PAD, matched 1:3 to control subjects. RESULTS: Levels of OxPL/apoB
      were positively associated with risk of PAD in men and women: pooled relative
      risk: 1.37, 95% confidence interval: 1.19 to 1.58 for each 1-SD increase after
      adjusting age, smoking, fasting status, month of blood draw, lipids, body mass
      index, and other cardiovascular disease risk factors. Lp(a) was similarly
      associated with risk of PAD (pooled adjusted relative risk: 1.36; 95% confidence
      interval: 1.18 to 1.57 for each 1-SD increase). Autoantibodies to MDA-LDL and
      ApoB-IC were not consistently associated with risk of PAD. CONCLUSIONS: OxPL/apoB
      were positively associated with risk of PAD in men and women. The major
      lipoprotein carrier of OxPL, Lp(a), was also associated with risk of PAD,
      reinforcing the key role of OxPL in the pathophysiology of atherosclerosis
      mediated by Lp(a).

PMID- 23541967
TI  - Niacin therapy lives for another day-maybe?

PMID- 23541968
TI  - Improving quality of life and functional capacity in atrial fibrillation and
      congestive heart failure.

PMID- 23541969
TI  - The softer side of bleeding.

PMID- 23541970
TI  - Fish oil and post-operative atrial fibrillation: a meta-analysis of randomized
      controlled trials.

PMID- 23541971
TI  - Interplay between right ventricular function and cardiac resynchronization
      therapy: an analysis of the CARE-HF trial (Cardiac Resynchronization-Heart
      Failure).
AB  - OBJECTIVES: The aim of this study was to investigate the impact of cardiac
      resynchronization therapy (CRT) on right ventricular (RV) function and the
      influence of RV dysfunction on the echocardiographic and clinical response to CRT
      among patients enrolled in the CARE-HF (Cardiac Resynchronization-Heart Failure)
      trial. BACKGROUND: Cardiac resynchronization therapy prolongs survival in
      appropriately selected patients with heart failure but the benefit might be
      diminished in patients with RV dysfunction. METHODS: Of 813 patients enrolled in
      the CARE-HF study, 688 had tricuspid plane systolic excursion (TAPSE) measured at
      baseline, and 345 of these were assigned to CRT. Their median (interquartile
      range) age was 66 (58 to 71) years, left ventricular (LV) ejection fraction was
      24% (21% to 28%), and TAPSE was 19 (16 to 22) mm. Baseline LV function and size
      and QRS duration were similar among TAPSE tertiles, but those in the worst
      tertile (TAPSE <17.4 mm) were more likely to have ischemic heart disease.
      RESULTS: Overall, CRT improved LV but not RV structure and function with little
      evidence of an interaction with TAPSE. During a median (interquartile range)
      follow-up of 748 (582 to 950) days, 213 deaths occurred. Patients with lower
      TAPSE had a higher mortality, regardless of assigned treatment (p < 0.001).
      Greater inter-ventricular mechanical delay, New York Heart Association functional
      class, mitral regurgitation, and N-terminal pro-B-type natriuretic peptide, lower
      TAPSE, and assignment to the control group were independently associated with
      higher mortality. Reduction in mortality with CRT was similar in each tertile of
      TAPSE. CONCLUSIONS: Right ventricular dysfunction is a powerful determinant of
      prognosis among candidates for CRT, regardless of treatment assigned, but did not
      diminish the prognostic benefits of CRT among patients enrolled in the CARE-HF
      trial. (Care-HF CArdiac Resynchronization in Heart Failure; NCT00170300).

PMID- 23541972
TI  - Platelet function tests in clinical cardiology: unfulfilled expectations.
AB  - This review is a critical evaluation of publications in the past decade on the
      usefulness of platelet function tests (PFTs) in clinical cardiology, in aiding
      diagnosis, predicting risk, and monitoring therapy. The ideal PFT should: 1)
      detect baseline platelet hyperreactivity; 2) allow individualization of
      antiplatelet medication; 3) predict thrombotic risk; and 4) predict bleeding
      risk. The practicalities of clinical cardiology demand rapid, accurate, and
      reliable tests that are simple to operate at the bedside and available 24 h a
      day, 7 days a week. Point-of-care PFTs most widely evaluated clinically include
      PFA-100 and VerifyNow. None of these tests can reliably detect platelet
      hyperreactivity and thus identify a prothrombotic state. Identification of
      antiplatelet nonresponsiveness or hyporesponsiveness is highly test specific, and
      does not allow individualization of therapy. The power of PFTs in predicting
      thrombotic events for a given individual is variable and often modest, and
      alteration of antithrombotic treatment on the basis of the results of PFTs has
      not been shown to alter clinical outcome. PFTs in current mainstream use cannot
      reliably assess bleeding risk. These tests have been in use for over a decade,
      but the hopes raised by PFTs in clinical practice remain unfulfilled. Although
      physiologically relevant measurement of platelet function now is more important
      than ever, a critical reappraisal of available techniques in light of clinical
      requirements is needed. The use of native blood, global stimulus instead of
      individual agonists, contribution of thrombin generation by activated platelets
      to the test results, and establishment of a PFT therapeutic range for each
      antiplatelet drug should be considered and is discussed.

PMID- 23541973
TI  - Impact of baseline heart failure burden on post-implantable cardioverter
      defibrillator mortality among medicare beneficiaries.
AB  - OBJECTIVES: This study sought to assess the impact of baseline heart failure (HF)
      burden on survival with primary implantable cardioverter-defibrillator (ICD)
      among Medicare recipients. BACKGROUND: Survival after primary ICD implantation
      may differ between trial and Medicare populations. METHODS: Linking data from the
      CMS (Centers for Medicare and Medicaid Services) ICD registry and the Medicare
      files (2005 to 2009), we identified primary ICD recipients age >=66 years with
      ejection fraction <=35%. Number of previous HF hospitalizations (prev-HF-hosp)
      and length of hospitalization prior to implantation were used to define HF
      burden. Crude all-cause mortality was estimated. Adjusted hazard ratios (HR) were
      derived from Cox models. RESULTS: Of 66,974 ICD recipients (73% men, 88% white,
      mean age 75 years), 11,876 died (average follow-up = 1.4 years), with 3-year
      mortality of 31%. Among patients with no prev-HF-hosp, 3-year mortality was 27%
      compared with 63% in those with >=3 prev-HF-hosp (adjusted HR: 1.8). Among
      patients with same-day implantation, 3-year mortality was 25% compared with 53%
      in those with >1-week hospitalization days prior to implantation (adjusted HR:
      1.9). Mortality at 3-year follow-up among the 31,685 ICD recipients with no prev
      HF-hosp and same-day implantation (low HF burden) was similar to that in trials
      (22%). CONCLUSIONS: Nearly one-third of Medicare ICD recipients died within 3
      years, reflecting a population with more advanced age and disease than seen in
      trial populations for primary prevention ICD. Nearly one-half of Medicare
      recipients had a low HF burden and had a survival similar to trial ICD
      recipients. Future research is warranted to understand the effectiveness of
      primary ICD implantation among Medicare beneficiaries with heavy HF burdens.

PMID- 23541974
TI  - Rapid-rate nonsustained ventricular tachycardia found on implantable cardioverter
      defibrillator interrogation: relationship to outcomes in the SCD-HeFT (Sudden
      Cardiac Death in Heart Failure Trial).
AB  - OBJECTIVES: The aim of this study was to examine rapid-rate nonsustained
      ventricular tachycardia (RR-NSVT) during routine implantable cardioverter
      defibrillator (ICD) evaluation in patients with heart failure and its
      relationship to outcomes. BACKGROUND: The clinical implications of RR-NSVT
      identified during routine ICD interrogation are unclear. In this study, the
      occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD
      HeFT (Sudden Cardiac Death in Heart Failure Trial) were examined. METHODS: The
      811 patients who received ICDs in SCD-HeFT constituted the study population. The
      occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD
      HeFT were examined. RESULTS: RR-NSVT was documented on ICD interrogation in 186
      of 811 patients (22.9%). The mean duration of RR-NSVT was 26.4 +/- 9.1 beats (7.5
      +/- 2.6 s), with a mean cycle length of 259 +/- 32 ms. Polymorphic RR-NSVT
      accounted for 56% of episodes. Compared with patients without RR-NSVT, those with
      RR-NSVT were less likely to be taking beta-blockers, statins, or aspirin at
      enrollment. After adjusting for other known predictors of mortality in SCD-HeFT,
      RR-NSVT was independently associated with appropriate ICD shocks (hazard ratio:
      4.25; 95% confidence interval: 2.94 to 6.14; p < 0.0001), with all-cause
      mortality (hazard ratio: 2.40; 95% confidence interval: 1.62 to 3.54; p <
      0.0001), and with a composite of all-cause mortality and appropriate ICD shocks
      (hazard ratio: 3.03; 95% confidence interval: 2.21 to 4.15; p < 0.0001).
      CONCLUSIONS: RR-NSVT identified on routine ICD interrogation should be considered
      an important clinical event. RR-NSVT during ICD interrogation is associated with
      appropriate ICD shocks and all-cause mortality. The clinical evaluation of
      patients with RR-NSVT should include intensification of medical therapy,
      particularly beta-blockers, or other appropriate clinical interventions. (Sudden
      Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609).

PMID- 23541975
TI  - Nuisance bleeding with prolonged dual antiplatelet therapy after acute myocardial
      infarction and its impact on health status.
AB  - OBJECTIVES: The purpose of this study was to examine the incidence of nuisance
      bleeding after AMI and its impact on QOL. BACKGROUND: Prolonged dual antiplatelet
      therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce
      ischemic events, but it is associated with increased rates of major and minor
      bleeding. The incidence of even lesser degrees of post-discharge "nuisance"
      bleeding with DAPT and its impact on quality of life (QOL) are unknown. METHODS:
      Data from the 24-center TRIUMPH (Translational Research Investigating Underlying
      Disparities in Acute Myocardial Infarction Patients' Health Status) study of
      3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used
      to investigate the incidence of nuisance bleeding (defined as Bleeding Academic
      Research Consortium type 1). Baseline characteristics associated with "nuisance"
      bleeding and its association with QOL, as measured by the EuroQol 5 Dimension
      visual analog scale, and subsequent re-hospitalization were examined. RESULTS:
      Nuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in
      1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline
      bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance
      bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1
      month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to
      1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month
      was independently associated with a decrement in QOL at 1 month (-2.81 points on
      EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and
      nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI:
      0.95 to 1.52). CONCLUSIONS: Nuisance bleeding is common in the year after AMI,
      associated with ongoing use of DAPT, and independently associated with worse QOL.
      Improved selection of patients for prolonged DAPT may help minimize the incidence
      and adverse consequences of nuisance bleeding.

PMID- 23541977
TI  - The low expression of leukemia inhibitory factor in endometrium: possible
      relevant to unexplained infertility with multiple implantation failures.
AB  - Unexplained infertility affects 25% of infertile couples. Cytokines and growth
      factors have been suggested to play an important role in the initial process of
      successful implantation in humans and failures in their production may be a cause
      of unexplained infertility. Leukemia inhibitory factor (LIF) and Interleukin-6
      (IL-6) have demonstrated their importance in implantation in both animal and
      human studies. Lower expression of LIF is found in proliferative phase and
      maximal expression is found in secretory phase of the menstrual cycle. Lower
      expression of LIF is also found in secretory phase endometrium in patients with
      infertility. However, studies investigating whether the levels of LIF in
      proliferative phase are associated with multiple implantation failures (MIFs) are
      limited. 30 Endometrial biopsies in proliferative phase from unexplained
      infertile women with MIF with normal hormone levels were collected. The
      expression of LIF, IL-6 and its receptor gp130 were measured by
      immunohistochemistry and western blotting. Moderate expression of LIF in the
      proliferative phase and high expression of LIF in the secretory phase were found
      in fertile women. However, lower expression of LIF was found in unexplained
      infertile women with MIF compared to fertile women. There was no difference in
      endometrial IL-6 and gp130 expression between unexplained infertile women with
      MIF and fertile women. LIF expression is independent of the process of embryo and
      dependent partially on the maternal sex hormone levels. Our data suggest that the
      initial lower expression of LIF in proliferative phase may be one of the causes
      for multiple failure of implantation.

PMID- 23541976
TI  - Association between interleukin 10 gene -1082 A/G polymorphism and the risk of
      type 2 diabetes mellitus: a meta-analysis of 4250 subjects.
AB  - Increasing evidence suggests that interleukin 10 (IL 10) gene -1082 A/G
      (rsl800896) polymorphism may be associated with an increased risk of type 2
      diabetes mellitus (T2DM). However, the results are inconsistent. The aim of this
      study is to analyze the association between this variant and the T2DM risk by
      meta-analysis. PubMed, Embase, Web of Science, and Google Scholar were searched
      from January 1, 1989 to February 17, 2012, as well as hand searching of the
      references of identified articles were performed. All the statistical tests were
      performed using Stata 11.0. Seven case-control studies were identified, covering
      a total of 1879 T2DM cases and 2371 controls. The results showed evidence of
      significant association between IL 10 gene -1082 A/G polymorphism and T2DM risk
      (for G/G+G/A vs. A/A: OR=1.21, 95% CI=1.05-1.40, p=0.010, p=0.040 after
      Bonferroni testing). In the subgroup analysis by ethnicity, no significant
      association was found between IL 10 gene -1082 A/G polymorphism and T2DM risk in
      Europeans. In summary, results from this meta-analysis provide evidence that IL
      10 gene -1082 G allele is associated with increased risk of T2DM.

PMID- 23541978
TI  - Does autoimmunity play a part in the pathogenesis of glaucoma?
AB  - Glaucoma is a chronic neurodegenerative disease and one of the leading causes of
      blindness. Several risk factors have been described, e.g. an elevated intraocular
      pressure (IOP), oxidative stress or mitochondrial dysfunction. Additionally,
      alterations in serum antibody profiles of glaucoma patients, upregulation (e.g.
      anti-HSP60, anti-MBP) and downregulation (e.g. anti-14-3-3), have been described,
      but it still remains elusive if the autoantibodies seen in glaucoma are an
      epiphenomenon or causative. However, it is known that elicited autoimmunity
      causes retinal ganglion cell loss resulting in glaucomatous-like damage and
      according to the autoaggressive nature of some autoantibodies we found antibody
      deposits in human glaucomatous retinae in a pro-inflammatory environment.
      Furthermore, glaucomatous serum has the potential to influence neuroretinal cell
      regulatory processes. Importantly, we demonstrate that some autoantibodies hold
      neuroprotective potential for neuroretinal cells. The protective nature of
      autoantibodies and the molecular mechanisms underlying the very sensitive
      equilibrium between autoaggression and protection remain subject of future
      examinations and offer promising target sites for new therapeutic approaches.
      Additionally, the changes in antibody profiles could be used as highly sensitive
      and specific marker for diagnostics purposes. Early diagnosis and intervention in
      risk patients would offer the chance of early treatment and to slow down the
      progression of glaucoma and delay the resulting blindness. 

PMID- 23541979
TI  - Imaging meibomian glands on a patient with chalazia in the upper and lower lids:
      a case report.
AB  - AIM: To describe the meibomian gland (MG) appearance in a case of eyelid
      chalazia, using a novel meibography method. METHODS: A 29-year-old female of
      South Asian origin presented with mild swelling in the lower lid of the left eye.
      The patient also presented with a history of a recurrent chalazion in the upper
      lid of the same eye, which later progressed to an active chalazion. A chalazion
      also developed in the upper lid of the right eye. Meibography was performed using
      a novel Keratograph (Keratograph 4, OCULUS, Wetzlar, Germany) to evaluate the
      structure of the MG in the area affected by the chalazia. RESULTS: The area of
      the recurrent chalazion in the upper left lid showed partial and/or complete MG
      loss. The active chalazia in the lower left lid and the upper right lid showed
      inflammation and MG drop out at the affected site. The inflammation was found to
      be reduced during the follow-up visits, however disappearance of MG very specific
      to the region of the chalazion was observed. CONCLUSION: The Keratograph 4 was
      able to image the MG structures clearly, allowing the clinician to monitor the
      progression of chalazia and the MG loss in the affected areas.

PMID- 23541980
TI  - Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay
      (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral
      replication.
AB  - Nonsense-mediated mRNA decay (NMD) is an essential and conserved cellular mRNA
      quality control mechanism. RNA signals to express viral genes from overlapping
      open reading frames potentially initiate NMD, nevertheless it is not clear
      whether viral RNAs are sensitive to NMD or if viruses have evolved mechanisms to
      evade NMD. Here we demonstrate that the genomic and full-length mRNAs of Human-T
      cell Leukemia Virus type-I (HTLV-1), a retrovirus responsible for Adult T-cell
      Leukemia (ATL), are sensitive to NMD. They exhibit accelerated turnover in NMD
      activated cells, while siRNA-mediated knockdown of NMD-master-regulator, UPF1,
      promotes enhanced stability of them. These effects on RNA stability were
      recapitulated by a reporter construct encoding the HTLV-1 translational
      frameshift signal of gag-pol. In agreement with the RNA stability, viral protein
      expression from the integrated provirus was inversely correlated with cellular
      NMD activity. We further demonstrated that the viral RNA-binding protein, Rex,
      approves the stability of viral RNA by inhibiting NMD. Significantly, Rex
      establishes a general block to NMD, as both NMD-responsive reporter transcripts
      and natural host-encoded NMD substrates were stabilized in the presence of Rex.
      Thus, we suggest that Rex not only stabilizes viral transcripts, but also
      perturbs cellular mRNA metabolism and host cell homeostasis via inhibition of
      NMD.

PMID- 23541981
TI  - Characterizing the intracellular distribution of metabolites in intact Chlamydia
      infected cells by Raman and two-photon microscopy.
AB  - Chlamydia species are obligate intracellular pathogens that proliferate only
      within infected cells. Currently, there are no known techniques or systems that
      can probe the spatial distribution of metabolites of interest within intact
      Chlamydia-infected cells. Here we investigate the ability of Raman microscopy to
      probe the chemical composition of different compartments (nucleus, inclusion, and
      cytoplasm) of Chlamydia trachomatis-infected epithelial cells. The overall
      intensity of the Raman spectrum is greatest in the inclusions and lowest in the
      cytoplasm in fixed cells. Difference spectra generated by normalizing to the
      intensity of the strong 1004 cm(-1) phenylalanine line show distinct differences
      among the three compartments. Most notably, the concentrations of adenine are
      greater in both the inclusions and the nucleus than in the cytoplasm, as seen by
      Raman microscopy. The source of the adenine was explored through a complementary
      approach, using two-photon microscopy imaging. Autofluorescence measurements of
      living, infected cells show that the adenine-containing molecules, NAD(P)H and
      FAD, are present mainly in the cytoplasm, suggesting that these molecules are not
      the source of the additional adenine signal in the nucleus and inclusions.
      Experiments of infected cells stained with a DNA-binding dye, Hoechst 33258,
      reveal that most of the DNA is present in the nucleus and the inclusions,
      suggesting that DNA/RNA is the main source of the additional Raman adenine signal
      in the nucleus and inclusions. Thus, Raman and two-photon microscopy are among
      the few non-invasive methods available to investigate cells infected with
      Chlamydia and, together, should also be useful for studying infection by other
      intracellular pathogens that survive within intracellular vacuoles.

PMID- 23541982
TI  - Potential diagnostic applications of side chain oxysterols analysis in plasma and
      cerebrospinal fluid.
AB  - The neurospecific cholesterol 24-hydroxylase converts excess brain cholesterol
      into 24S-hydroxycholesterol (24OHC) which, via the liver X receptor (LXR), can
      increase the expression and synthesis of astrocyte ApoE. 24OHC effluxes directly
      from brain into plasma where it is considered an indicator of brain cholesterol
      turnover. It is reduced in neurodegenerative disease states proportionally to the
      severity of disease and the degree of brain atrophy. In the early phases of
      active disease, a higher rate of turnover may result in transitory increases in
      plasma 24OHC. Less than 1% of the total brain excretion of 24OHC occurs via the
      cerebrospinal fluid (CSF) whereas almost all 27-hydroxycholesterol (27OHC)
      excretion is dependent on the function of the blood-cerebrospinal fluid barrier.
      Iincreased CSF oxysterols were found in patients with neurodegenerative and
      neuroinflammatory diseases in the presence of barrier dysfunction. In
      neurodegeneration, free cholesterol released from dying cells may engulf neurons.
      Cholesterol also increases Amyloid beta (Abeta) deposition and tau pathology.
      ApoE, 24OHC, tau and soluble APP were correlated in Alzheimer disease (AD)
      samples. Excess of cholesterol converted into 24OHC may up-regulate ApoE
      synthesis which is a scavenger for Abeta and Tau. In AD this protective mechanism
      seems to be inefficient, probably due to the presence of high concentrations of
      27OHC, microvascular dysfunction and the decreased efficiency of ApoE4 as lipid
      transporter and Abeta scavenger. 24OHC itself was cytotoxic. Analysis of side
      chain oxysterols in the CSF is likely to provided useful information about
      cholesterol metabolism and ApoE function in the pathogenesis of AD.

PMID- 23541983
TI  - Chemosensitization potential of P-glycoprotein inhibitors in malaria parasites.
AB  - Members of the ATP-binding cassette (ABC)-type transporter superfamily have been
      implicated in multidrug resistance in malaria, and various mechanistic models
      have been postulated to explain their interaction with diverse antimalarial
      drugs. To gain insight into the pharmacological benefits of inhibiting ABC-type
      transporters in malaria chemotherapy, we investigated the in vitro
      chemosensitization potential of various P-glycoprotein inhibitors. A fluorescent
      chloroquine derivative was synthesized and used to assess the efflux dynamics of
      chloroquine in MDR and wild type Plasmodium falciparum parasites. This novel
      BODIPY-based probe accumulated in the digestive vacuole (DV) of CQ-sensitive
      parasites but less so in MDR cells. Pre-exposure of the MDR parasites to non
      cytocidal concentrations of unlabeled chloroquine resulted in a diffused
      cytoplasmic retention of the probe whereas a similar treatment with the CQR
      reversing agent, chlorpheniramine, resulted in DV accumulation. A diffused
      cytoplasmic distribution of the probe was also obtained following treatment with
      the P-gp specific inhibitors zosuquidar and tariquidar, whereas treatments with
      the tyrosine kinase inhibitors gefitinib or imatinib produced a partial
      accumulation within the DV. Isobologram analyses of the interactions between
      these inhibitors and the antimalarial drugs chloroquine, mefloquine, and
      artemisinin revealed distinct patterns of drug synergism, additivity and
      antagonism. Taken together, the data indicate that competitive tyrosine kinase
      and noncompetitive P-glycoprotein ATPase-specific inhibitors represent two new
      classes of chemosensitizing agents in malaria parasites, but caution against the
      indiscriminate use of these agents in antimalarial drug combinations.

PMID- 23541984
TI  - Gamma scintigraphy in the analysis of ketoprofen behaviour from matrix tablets.
AB  - The aim of this work was to study in vitro and in vivo the behaviour of matrix
      tablets (quick and extended release) containing ketoprofen (KTP) as a model drug
      and cellulose ether polymers, using gamma scintigraphy. The matrix tablets were
      prepared by the direct compression method and labelled by incorporating a drop of
      technetium ((99m)Tc). It was spectrophotometricaly confirmed that the
      radioisotope inclusion did not modify the kinetics of KTP release. In vitro
      studies were carried out for the tablets using the paddle method of the USP
      35/NF30. The images were processed by defining regions of interest over the
      tablet (99m)Tc and the percentage of remaining activity/time curves were
      generated for both formulations. In vitro gamma scintigraphy studies showed
      significant differences (p<0.05) between both formulations. Identical results
      were obtained from the in vivo studies. In vivo tests were performed on five
      healthy volunteers. The scintigraphy images were acquired during 2.5 and 7.5h for
      quick and extended release formulations, respectively. The position of the
      extended release formulation tablet along the gastrointestinal tract (GIT) was
      assessed. The described results demonstrate the in vitro/in vivo correlation for
      the drug release profile and exhibit the importance of gamma scintigraphy for the
      drug location through the GIT.

PMID- 23541985
TI  - Preformulation study of methazolamide for topical ophthalmic delivery:
      physicochemical properties and degradation kinetics in aqueous solutions.
AB  - Methazolamide (MTZ) is an anti-glaucoma drug. The present paper aims to
      characterize the physicochemical properties and degradation kinetics of MTZ to
      provide a basis for topical ophthalmic delivery. With the increase in pH (pH 5.5
      8.0) of aqueous solution, the solubility of the compound increased while the
      partition coefficient (Ko/w) which was estimated in the system n-octanol/aqueous
      solution decreased. The degradation of MTZ in aqueous solution followed pseudo
      first-order kinetic. The degradation rate kpH is the rate in the absence of
      buffer catalysis. Plotting the natural logarithm of kpH versus the corresponding
      pH value gave a V-shaped pH-rate profile with a maximum stability at pH 5.0. The
      degradation rate constants as a function of the temperature obeyed the Arrhenius
      equation (R(2)=0.9995 at pH 7.0 and R(2)=0.9955 at pH 9.0, respectively). A
      decrease in ionic strength and buffer concentration displayed a stabilizing
      effect on MTZ. Buffer species also influenced the MTZ hydrolysis. Phosphate
      buffer system was more catalytic than tris and borate buffer systems. In brief,
      it is important to consider the physicochemical properties and the stability of
      MTZ during formulation.

PMID- 23541986
TI  - Influence of drug content, type of semi-solid vehicle and rheological properties
      on the skin penetration of the model drug fludrocortisone acetate.
AB  - Throughout Europe, topical creams containing corticosteroids are diluted with
      various neutral cream bases to meet the specific needs of patients. Even though
      this practice has been common for years, its effect has not been thoroughly
      investigated and so the effectiveness of the diluted topical steroidal creams is
      difficult to predict. In the present study, the model drug fludrocortisone
      acetate was incorporated into three cream bases of different hydrophilicity that
      are commonly used in Austria. Different final drug concentrations were chosen for
      comparative studies. Additionally, a semi-solid preparation developed by our
      group was investigated for comparison. These formulations were tested in
      diffusion and tape stripping experiments. Diffusion cell studies showed that
      changes in drug concentration do not necessarily change the skin permeation
      behaviour in vitro. The tape stripping protocol was successfully optimised for
      investigation of semi-solid preparations to provide reproducible and accurate
      results despite the challenges of investigating semi-solid formulations. The
      results showed that tape stripping experiments are more suitable to elucidate
      subtle differences between formulations. The composition of the cream bases
      exhibited stronger effects on the skin penetration of the steroidal drug
      irrespective of its concentration than the rheological properties. No correlation
      between formulation viscosity and skin penetration was found.

PMID- 23541987
TI  - Biomarkers of lipid peroxidation in clinical material.
AB  - BACKGROUND: Free radical-mediated lipid peroxidation has been implicated in a
      number of human diseases. Diverse methods have been developed and applied to
      measure lipid peroxidation products as potential biomarkers to assess oxidative
      stress status in vivo, discover early indication of disease, diagnose progression
      of disease, and evaluate the effectiveness of drugs and antioxidants for
      treatment of disease and maintenance of health, respectively. However,
      standardized methods are not yet established. SCOPE OF REVIEW: Characteristics of
      various lipid peroxidation products as biomarkers are reviewed on the basis of
      mechanisms and dynamics of their formation and metabolism and also on the methods
      of measurement, with an emphasis on the advantages and limitations. MAJOR
      CONCLUSIONS: Lipid hydroxides such as hydroxyoctadecadienoic acids (HODE),
      hydroxyeicosatetraenoic acids (HETE), and hydroxycholesterols may be recommended
      as reliable biomarkers. Notably, the four HODEs, 9-cis,trans, 9-trans,trans, 13
      cis,trans, and 13-trans,trans-HODE, can be measured separately by LC-MS/MS and
      the trans,trans-forms are specific marker of free radical mediated lipid
      peroxidation. Further, isoprostanes and neuroprostanes are useful biomarker of
      lipid peroxidation. It is important to examine the distribution and temporal
      change of these biomarkers. GENERAL SIGNIFICANCE: Despite the fact that lipid
      peroxidation products are non-specific biomarkers, they will enable to assess
      oxidative stress status, disease state, and effects of drugs and antioxidants.
      This article is part of a Special Issue entitled Current methods to study
      reactive oxygen species - pros and cons and biophysics of membrane proteins.
      Guest Editor: Christine Winterbourn.

PMID- 23541988
TI  - Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine
      transferrin receptor for cellular iron acquisition.
AB  - BACKGROUND: The long held view is that mammalian cells obtain transferrin (Tf)
      bound iron utilizing specialized membrane anchored receptors. Here we report
      that, during increased iron demand, cells secrete the glycolytic enzyme
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which enhances cellular uptake
      of Tf and iron. METHODS: These observations could be mimicked by utilizing
      purified GAPDH injected into mice as well as when supplemented in culture medium
      of model cell lines and primary cell types that play a key role in iron
      metabolism. Transferrin and iron delivery was evaluated by biochemical,
      biophysical and imaging based assays. RESULTS: This mode of iron uptake is a
      saturable, energy dependent pathway, utilizing raft as well as non-raft domains
      of the cell membrane and also involves the membrane protein CD87 (uPAR). Tf
      internalized by this mode is also catabolized. CONCLUSIONS: Our research
      demonstrates that, even in cell types that express the known surface receptor
      based mechanism for transferrin uptake, more transferrin is delivered by this
      route which represents a hidden dimension of iron homeostasis. GENERAL
      SIGNIFICANCE: Iron is an essential trace metal for practically all living
      organisms however its acquisition presents major challenges. The current paradigm
      is that living organisms have developed well orchestrated and evolved mechanisms
      involving iron carrier molecules and their specific receptors to regulate its
      absorption, transport, storage and mobilization. Our research uncovers a hidden
      and primitive pathway of bulk iron trafficking involving a secreted receptor that
      is a multifunctional glycolytic enzyme that has implications in pathological
      conditions such as infectious diseases and cancer.

PMID- 23541989
TI  - Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus
      officinalis, is exerted through the C/EBPs and PPARgamma pathways at the onset of
      the differentiation program.
AB  - BACKGROUND: Obesity is a serious health problem all over the world, and
      inhibition of adipogenesis constitutes one of the therapeutic strategies for its
      treatment. Carnosic acid (CA), the main bioactive compound of Rosmarinus
      officinalis extract, inhibits 3T3-L1 preadipocytes differentiation. However, very
      little is known about the molecular mechanism responsible for its antiadipogenic
      effect. METHODS: We evaluated the effect of CA on the differentiation of 3T3-L1
      preadipocytes analyzing the process of mitotic clonal expansion, the level of
      adipogenic markers, and the subcellular distribution of C/EBPbeta. RESULTS: CA
      treatment only during the first day of 3T3-L1 differentiation process was enough
      to inhibit adipogenesis. This inhibition was accompanied by a blockade of mitotic
      clonal expansion. CA did not interfere with C/EBPbeta and C/EBPdelta mRNA levels
      but blocked PPARgamma, and FABP4 expression. C/EBPbeta has different forms known
      as LIP and LAP. CA induced an increase in the level of LIP within 24h of
      differentiation, leading to an increment in LIP/LAP ratio. Importantly,
      overexpression of LAP restored the capacity of 3T3-L1 preadipocytes to
      differentiate in the presence of CA. Finally, CA promoted subnuclear de
      localization of C/EBPbeta. CONCLUSIONS: CA exerts its anti-adipogenic effect in a
      multifactorial manner by interfering mitotic clonal expansion, altering the ratio
      of the different C/EBPbeta forms, inducing the loss of C/EBPbeta proper
      subnuclear distribution, and blocking the expression of C/EBPalpha and PPARgamma.
      GENERAL SIGNIFICANCE: Understanding the molecular mechanism by which CA blocks
      adipogenesis is relevant because CA could be new a food additive beneficial for
      the prevention and/or treatment of obesity.

PMID- 23541990
TI  - Use of a modified removable partial denture as a marsupialization stent in a
      pediatric patient.

PMID- 23541991
TI  - Use of intraoperative fluorescent angiography to assess and optimize free tissue
      transfer in head and neck reconstruction.
AB  - PURPOSE: Composite tissue defects in the head and neck region present unique
      challenges. Definitive head and neck reconstruction of these cases is often
      complicated by complex 3-dimensional defects that may require multiple flap or
      chimeric flap procedures. These advanced techniques can have serious
      repercussions should poor perfusion of the flap cause flap failure, which can be
      devastating. MATERIALS AND METHODS: A retrospective review was completed for
      those complex reconstructions using free tissue transfers and fluorescent
      indocyanine green angiography (Lifecell SPY Elite imaging, Lifecell Corporation,
      Bridgewater, NJ) at Walter Reed National Military Medical Center over a 24-month
      period. Data analyzed included flap type (myocutaneous, osteocutaneous, or
      fasciocutaneous), flap success and failure rates, and complications. These also
      were compared with data from the institution before the study period and the
      incorporation of SPY technology. RESULTS: Sixty-one free flaps, including 11 head
      and neck flaps, were performed. The head and neck flaps included 1 latissimus, 3
      gracilis, 1 vastus lateralis, 4 anterior lateral thigh, and 2 fibular flaps. The
      overall success rate was 98.4%; 1 flap was lost (1.6%) and 2 flaps developed
      partial flap necrosis (3.3%). Where SPY Elite was used, there was no unpredicted
      partial flap necrosis. The only total flap loss was related to a hypercoagulable
      condition. CONCLUSIONS: Free tissue transfer can be technically challenging,
      especially in complex head and neck reconstruction. An algorithmic approach using
      SPY Elite imaging aids in pedicle location, angiosomal assessment, anastomotic
      flow visualization, and cutaneous and osteocutaneous flap perfusion assessment.
      This objective tool can assist the reconstructive surgeon in avoiding perfusion
      related complications and total and partial flap losses, thus improving patient
      outcomes.

PMID- 23541992
TI  - Orthognathic surgery for correction of patients with mandibular excess: don't
      forget to assess the gonial angle.
AB  - PURPOSE: To evaluate the gonial angle (GA) and associated factors that can
      contribute to stability after bilateral sagittal split ramus osteotomy setback
      and Le Fort I advancement osteotomy for the treatment of patients with mandibular
      excess. MATERIALS AND METHODS: This retrospective study included 42 randomly
      selected, adult patients. Lateral cephalometric radiographs were obtained before
      and 1 week and 1 year after surgery. Patients in group 1 (n = 18) had a GA
      smaller than 125 degrees  and those in group 2 (n = 24) had a GA larger than 125
      degrees . Data were analyzed by analysis of variance and Pearson correlations.
      Multivariate linear regression analysis was used to identify factors that
      influenced postsurgical stability. RESULTS: Mean surgical changes were similar in
      the 2 groups. The mandible was set back an average of 5.4 mm in group 1 and 6.4
      mm in group 2, whereas the maxilla was advanced 2.5 mm in group 1 and 1.7 mm in
      group 2. Statistically significant postoperative changes were noted for group 1
      only. Relapse was found at the innermost point of the contour of the mandible
      between the incisor tooth and bony chin and the pogonion for the horizontal
      landmarks; the innermost point of the contour of the maxilla between the anterior
      nasal spine and incisor tooth and the menton for the vertical landmarks; and the
      GA, the angle between the sella-nasion line and the innermost point of the
      contour of the mandible between the incisor tooth and bony chin, and the esthetic
      plane to the upper lip for the dimensional landmarks. No statistically
      significant changes were noted for group 2 (GA >125 degrees ). CONCLUSION:
      Patients with a preoperative GA smaller than 125 degrees  have a greater risk of
      relapse after receiving bilateral sagittal split ramus osteotomy setback and Le
      Fort I advancement for the treatment of mandibular excess. Patients with a
      preoperative GA larger than 125 degrees  appear to have a more predictable
      procedure.

PMID- 23541993
TI  - 3-dimensional computed tomographic analysis of the pharynx in adult patients with
      unrepaired isolated cleft palate.
AB  - PURPOSE: This study investigated 3D differences of the pharynx in adult patients
      with unrepaired isolated cleft palate (ICP) versus normal adults using cone-beam
      computed tomography (CBCT). PATIENTS AND METHODS: CBCT data of 32 adult patients
      with nonsyndromic unrepaired ICP and 30 normal controls were acquired. Image
      processing and analyses were performed using Mimics (Materialise NV, Leuven,
      Belgium). Linear, planar, and volumetric measurements and comparisons were
      performed between patients with ICP and controls. Interobserver and intraobserver
      reliabilities of 3D pharyngeal analysis were determined by the Pearson
      correlation coefficient. Statistical analyses comparing patients with ICP to
      normal adults were performed using independent-samples t test, with the
      significance threshold set at P = .05. RESULTS: Interobserver and intraobserver
      reliabilities were high. Pearson correlation coefficients ranged from 0.992 to
      0.999 for interobserver measurements and from 0.994 to 0.999 for intraobserver
      measurements. Anterior height (P = .000), total depth (P = .003), and floor
      length (P = .034) of the bony nasopharynx; posteroanterior diameter of the
      pharyngeal airway at the palatal plane (P = .000); cross-sectional area of the
      pharyngeal airway at the palatal plane (P = .000); total volume (P = .031);
      volume above the palatal plane (P = .024); and the volume between the palatal
      plane and the plane of the most anterior point on the inferior margin of the
      outline of the body of the second cervical vertebra (P = .022) were larger in
      patients with ICP. CONCLUSIONS: This imaging study showed an enlarged nasopharynx
      in the sagittal plane and increased nasopharyngeal airway volume at the palatal
      plane in patients with ICP.

PMID- 23541994
TI  - Closing the loop in legged neuromechanics: an open-source computer vision
      controlled treadmill.
AB  - The neural circuitry that controls legged locomotion is exquisitely state
      dependent. The response to a perturbation at one phase of the locomotor cycle is
      very different from another. As such, tools that enable closed loop experiments
      in which freely moving animals can be precisely perturbed, either neurally or
      mechanically, will improve our ability to probe the locomotor control
      architecture. Because locomotion emerges from the coupled interaction of the
      nervous system, musculoskeletal system, and physics of the moving body, ideally
      an experimenter could simultaneously perturb the nervous system, mechanics of the
      moving animal, or both, at precise moments during well defined locomotor
      behaviour. Combining the new technique of optogenetics with closed loop tracking
      of state and fast mechanical perturbations would make this possible. Here we
      present a computer vision feedback controlled treadmill designed to enable such
      perturbations. We show that insects (cockroaches Blaberus discoidalis) and mice
      (Mus mus; C57BL/6) run freely, with preferred speeds in agreement with the
      literature, over many strides, on the system. We demonstrate the utility of the
      closed loop system by automatically gathering high speed video (HSV) data when
      the running animal meets specific operational criteria; here, running within a
      restricted range of speeds near the midline of the treadmill for a minimum of 2s.
      We quantify the mouse's gait from HSV data with a phase-based approach,
      confirming a normal trotting gait. These results demonstrate the system's
      potential for dissecting the neuromechanical basis of legged locomotion through
      closed-loop experimental design.

PMID- 23541995
TI  - A low-cost technique to cryo-protect and freeze rodent brains, precisely aligned
      to stereotaxic coordinates for whole-brain cryosectioning.
AB  - A major challenge in the histological sectioning of brain tissue is achieving
      accurate alignment in the standard coronal, horizontal, or sagittal planes.
      Correct alignment is desirable for ease of subsequent analysis and is a
      prerequisite for computational registration and algorithm-based quantification of
      experimental data. We have developed a simple and low-cost technique for whole
      brain cryosectioning of rodent brains that reliably results in a precise
      alignment of stereotactic coordinates. The system utilises a 3-D printed model of
      a mouse brain to create a tailored cavity that is used to align and support the
      brain during freezing. The alignment of the frozen block is achieved in relation
      to the fixed edge of the mold. The system also allows for two brains to be frozen
      and sectioned simultaneously. System components, procedural steps, and examples
      of the end results are presented. 

PMID- 23541996
TI  - State-trait arousal and daytime sleepiness after sleep restriction.
AB  - The importance of an arousal system in the regulation of sleepiness has been
      widely recognised in contexts of insomnia theory and research. Arousal is also
      incorporated in some general models of sleepiness and is considered one of the
      principal factors regulating sleepiness in a model by De Valck and Cluydts
      (2003), in which arousal has both state and trait components. In the present
      experimental study, we explored the effects of state and trait components of
      arousal on subjective sleepiness and sleep latency during daytime. On a day after
      partial sleep deprivation, 28 good sleepers aged 18-26 years took part in two
      successive experimental conditions, in which the state arousal was manipulated by
      laboratory tasks. We measured physiological (heart rate, frequency of skin
      conductance responses) and subjective (Energy, Tension, Anxiety) indices of state
      arousal, while trait arousal was operationalised as electrodermal lability. After
      a moderately stressful task, which induced a relatively higher state arousal, the
      participants reported lower sleepiness and took longer to fall asleep than after
      a simple psychomotor task. Trait arousal was not associated with daytime
      sleepiness. The results of this study support the idea that short-term changes of
      state arousal are important for the regulation of sleepiness in good sleepers,
      even in a situation which is only moderately stressful.

PMID- 23541997
TI  - Excitatory versus inhibitory impairments in insomnia patients: an ERP study.
AB  - According to the neurocognitive perspective on insomnia, conditioned arousal
      results in impairment of information processing, as such interfering with normal
      sleep processes. In the present study, evening event-related potentials N100 and
      P200 were evaluated to assess hyperarousal in patients with insomnia and
      controls. 13 patients (mean age = 40.8) with polysomnographically verified sleep
      disruptions and 11 good sleepers (mean age = 45.4) were included. An auditory
      oddball paradigm was administered the evening of the polysomnography. N100 and
      P200 mean amplitudes and peak latencies at Fz and Cz were analyzed as a measure
      of respectively general arousability and inhibition of information processing.
      Patients experiencing insomnia were characterized by decreased P200 amplitudes
      compared to good sleepers. No significant differences were found for N100
      amplitudes and latencies of both ERP waves. These results suggest that this group
      of patients with objectified insomnia is characterized by an arousal impairment.
      However, there was no evidence of hyperarousal, considering the normal N100
      amplitudes. On the other hand, the inhibition of information processing was
      distorted. As such, the impairment of de-arousal or de-activation in insomnia is
      put forward as an additional factor within the arousal model.

PMID- 23541998
TI  - Effects of cannabis use on event related potentials in subjects at ultra high
      risk for psychosis and healthy controls.
AB  - Cannabis use has consistently been associated with psychotic symptoms as well as
      cognitive impairments. Moreover, its use may provoke subclinical psychotic
      symptoms and is associated with neuropsychological dysfunctions in subjects at
      ultra high risk (UHR) for developing psychosis. However, to our knowledge, no
      data are yet available on the relationship between cannabis use, UHR symptoms and
      information processing as assessed with event related potentials (ERP) in UHR
      subjects. This cross-sectional study therefore aimed to investigate N100, N200,
      P200 and P300 ERP components in 48 UHR subjects (19 cannabis users; UHR+C) and 50
      healthy controls (21 cannabis users; HC+C). Results showed smaller P300
      amplitudes in HC+C and UHR subjects compared to HC-C. Moreover, HC+C showed
      prolonged P300 and N200 latencies compared to HC-C and UHR-C. No significant ERP
      differences were found between UHR+C and UHR-C. Regarding the relationship
      between information processing and psychopathology, we found associations between
      ERP components and severity of UHR symptoms, findings being most pronounced for
      N100 latencies and P300 amplitudes and severity of general psychopathology and
      positive symptoms. We conclude that UHR subjects and healthy cannabis users
      demonstrate similar P300 amplitude reductions compared to non-using control
      subjects. In addition, the interrelation of cannabis use with prolonged ERP
      latencies may signify reduced information processing speed associated with
      cannabis use. Finally, our findings cautiously support the hypothesis that the
      clinical phenomena of the UHR state may be associated with abnormalities in
      stimulus processing.

PMID- 23541999
TI  - Activation of mitochondria-mediated apoptotic pathway in tri-ortho-cresyl
      phosphate-induced delayed neuropathy.
AB  - Previous studies suggest that abnormal neurons death has been implicated in
      organophosphate-induced delayed neuropathy (OPIDN). However, the precise
      mechanism of neuronal death in OPIDN remains largely unknown. In this study,
      adult hens were treated with a dosage of 750 mg/kg tri-ortho-cresyl phosphate
      (TOCP) by gavage, and then sacrificed on the time-points of 1, 5, 10, and 21 days
      after dosing TOCP, respectively. The apoptotic change of spinal cord neurons
      induced by TOCP was examined, and the role of mitochondria-mediated apoptosis of
      neurons during OPIDN was investigated. TUNEL assays showed that apoptotic neurons
      in hen spinal cords began to appear on day 5 following TOCP exposure.
      Immunohistochemistry and western blot analysis revealed a translocation of
      cytochrome C from mitochondria to cytoplasm after dosing TOCP. Moreover, the
      level of Bcl-2, Bcl-xl, Pro-caspase3 and Pro-caspase9 in hen spinal cord was
      significantly decreased, whereas that of Bax and cleaved-PARP was significantly
      elevated. Taken together, these findings indicate that the administration of TOCP
      can induce neuron apoptosis in hen spinal cords, which might be mediated by the
      activation of mitochondrial apoptotic pathway.

PMID- 23542000
TI  - A multi-locus timetree of surgeonfishes (Acanthuridae, Percomorpha), with revised
      family taxonomy.
AB  - We present the most comprehensive time-calibrated, species-level hypothesis of
      the timing of Acanthuridae (surgeonfishes and allies) evolution based on 76% of
      the extant diversity and nine genes. We recover two major acanthurid clades,
      Nasinae and Acanthurinae, and infer a much more recent Nasinae crown age (17 Ma)
      compared to a previous dating study for Naso. The Acanthurinae represent an older
      group that originated ~42 Ma, with most diversification occurring since the Early
      Miocene (beginning ~21 Ma). Our results strongly support a paraphyletic
      Acanthurus and Ctenochaetus, with multiple analyses recovering a clade grouping
      Ctenochaetus, A. nubilus and A. pyroferus. Contrary to previous studies, we also
      provide strong evidence that thick-walled, gizzard-like stomachs evolved only
      once within Acanthurus and that this morphology has a common origin in Acanthurus
      and Ctenochaetus. Based on our molecular analyses, in conjunction with the large
      body of morphological evidence, we recommend dissolving the genus Ctenochaetus
      into the genus Acanthurus.

PMID- 23542001
TI  - Molecular phylogeny, divergence times and biogeography of spiders of the
      subfamily Euophryinae (Araneae: Salticidae).
AB  - We investigate phylogenetic relationships of the jumping spider subfamily
      Euophryinae, diverse in species and genera in both the Old World and New World.
      DNA sequence data of four gene regions (nuclear: 28S, Actin 5C; mitochondrial:
      16S-ND1, COI) were collected from 263 jumping spider species. The molecular
      phylogeny obtained by Bayesian, likelihood and parsimony methods strongly
      supports the monophyly of a Euophryinae re-delimited to include 85 genera.
      Diolenius and its relatives are shown to be euophryines. Euophryines from
      different continental regions generally form separate clades on the phylogeny,
      with few cases of mixture. Known fossils of jumping spiders were used to
      calibrate a divergence time analysis, which suggests most divergences of
      euophryines were after the Eocene. Given the divergence times, several
      intercontinental dispersal events are required to explain the distribution of
      euophryines. Early transitions of continental distribution between the Old and
      New World may have been facilitated by the Antarctic land bridge, which
      euophryines may have been uniquely able to exploit because of their apparent cold
      tolerance. Two hot-spots of diversity of euophryines are discovered: New Guinea
      and the Caribbean Islands. Implications of the molecular phylogeny on the
      taxonomy of euophryines, and on the evolution of unusual genitalic forms and
      myrmecophagy, are also briefly discussed.

PMID- 23542002
TI  - Molecular phylogeny and revised classification of the haplotilapiine cichlid
      fishes formerly referred to as "Tilapia".
AB  - African cichlids formerly referred to as "Tilapia" represent a paraphyletic
      species assemblage belonging to the so called haplotilapiine lineage which gave
      rise to the spectacular East African cichlid radiations (EARs) as well as to
      globally important aquaculture species. We present a comprehensive molecular
      phylogeny of representative haplotilapiine cichlids, combining in one data set
      four mitochondrial and five nuclear loci for 76 species, and compare it with
      phylogenetic information of a second data set of 378 mitochondrial ND2 haplotypes
      representing almost all important "Tilapia" or Tilapia-related lineages as well
      as most EAR lineages. The monophyly of haplotilapiines is supported, as is the
      nested sister group relationship of Etia and mouthbrooding tilapiines with the
      remaining haplotilapiines. The latter are consistently placed in eight
      monophyletic clades over all datasets and analyses, but several dichotomous
      phylogenetic relationships appear compromised by cytonuclear discordant
      phylogenetic signal. Based on these results as well as on extensive morphological
      evidence we propose a novel generic and suprageneric classification including a
      (re-)diagnosis of 20 haplotilapiine cichlid genera and nine tribes. New tribes
      are provided for the former subgenera Coptodon Gervais, 1853, HeterotilapiaRegan,
      1920 and PelmatolapiaThys van den Audenaerde, 1969, in addition for "Tilapia"
      joka, Tilapia sensu stricto and Chilochromis, Etia, Steatocranus sensu stricto,
      the mouthbrooding tilapiines and for a clade of West African tilapiines.

PMID- 23542003
TI  - Reconstructing the phylogeny of aphids (Hemiptera: Aphididae) using DNA of the
      obligate symbiont Buchnera aphidicola.
AB  - Reliable phylogenetic reconstruction, as a framework for evolutionary inference,
      may be difficult to achieve in some groups of organisms. Particularly for
      lineages that experienced rapid diversification, lack of sufficient information
      may lead to inconsistent and unstable results and a low degree of resolution.
      Coincidentally, such rapidly diversifying taxa are often among the biologically
      most interesting groups. Aphids provide such an example. Due to rapid adaptive
      diversification, they feature variability in many interesting biological traits,
      but consequently they are also a challenging group in which to resolve phylogeny.
      Particularly within the family Aphididae, many interesting evolutionary questions
      remain unanswered due to phylogenetic uncertainties. In this study, we show that
      molecular data derived from the symbiotic bacteria of the genus Buchnera can
      provide a more powerful tool than the aphid-derived sequences. We analyze 255
      Buchnera gene sequences from 70 host aphid species and compare the resulting
      trees to the phylogenies previously retrieved from aphid sequences, only. We find
      that the host and symbiont data do not conflict for any major phylogenetic
      conclusions. Also, we demonstrate that the symbiont-derived phylogenies support
      some previously questionable relationships and provide new insights into aphid
      phylogeny and evolution.

PMID- 23542004
TI  - HDAC inhibitors dysregulate neural stem cell activity in the postnatal mouse
      brain.
AB  - The mammalian central nervous system (CNS) undergoes significant expansion
      postnatally, producing astrocytes, oligodendrocytes and inhibitory neurons to
      modulate the activity of neural circuits. This is coincident in humans with the
      emergence of pediatric epilepsy, a condition commonly treated with
      valproate/valproic acid (VPA), a potent inhibitor of histone deacetylases
      (HDACs). The sequential activity of specific HDACs, however, may be essential for
      the differentiation of distinct subpopulations of neurons and glia. Here, we show
      that different subsets of CNS neural stem cells (NSCs) and progenitors switch
      expression of HDAC1 and HDAC2 as they commit to a neurogenic lineage in the
      subventricular zone (SVZ) and dentate gyrus (DG). The administration of VPA for
      only one week from P7-P14, combined with sequential injections of thymidine
      analogs reveals that VPA stimulates a significant and differential decrease in
      the production and differentiation of progeny of NSCs in the DG, rostral
      migratory stream (RMS), and olfactory bulb (OB). Cross-fostering VPA-treated mice
      revealed, however, that a postnatal failure to thrive induced by VPA treatment
      had a greater effect on DG neurogenesis than VPA action directly. By one month
      after VPA, OB interneuron genesis was significantly and differentially reduced in
      both periglomerular and granule neurons. Using neurosphere assays to test if VPA
      directly regulates NSC activity, we found that short term treatment with VPA in
      vivo reduced neurosphere numbers and size, a phenotype that was also obtained in
      neurospheres from control mice treated with VPA and an alternative HDAC
      inhibitor, Trichostatin A (TSA) at 0 and 3 days in vitro (DIV). Collectively,
      these data show that clinically used HDAC inhibitors like VPA and TSA can perturb
      postnatal neurogenesis; and their use should be carefully considered, especially
      in individuals whose brains are actively undergoing key postnatal time windows of
      development. 

PMID- 23542006
TI  - A homology model of HIV-1 integrase and analysis of mutations designed to test
      the model.
AB  - Although there are structures of the different domains of human immunodeficiency
      virus type 1 (HIV-1) integrase (IN), there is no structure of the entire protein.
      The recently determined crystal structures of the prototype foamy virus (PFV) IN
      tetramer, in complexes with viral DNA, led to the generation of models of full
      length HIV-1 IN. These models were generated, in part, by superimposing the
      structures of the domains of HIV-1 IN onto the structure of full-length PFV IN.
      We developed a model for HIV-1 IN-based solely on its sequence alignment with PFV
      IN-that differs in several ways from the previous models. Specifically, in our
      model, the junction between the catalytic core domain and C-terminal domain
      adopts a helix-loop-helix motif that is similar to the corresponding segment of
      PFV IN and differs from the crystal structures of these two HIV-1 IN domains. The
      alignment of residues in the C-terminal domain also differs from the previous
      models. Our model can be used to explain the phenotype of previously published
      HIV-1 IN mutants. We made additional mutants, and the behavior of these new
      mutants provides additional support for the model.

PMID- 23542005
TI  - Alcohol exposure during development: Impact on the epigenome.
AB  - Fetal alcohol spectrum disorders represent a wide range of symptoms associated
      with in utero alcohol exposure. Animal models of FASD have been useful in
      determining the specific neurological consequences of developmental alcohol
      exposure, but the mechanisms of those consequences are unclear. Long-lasting
      changes to the epigenome are proposed as a mechanism of alcohol-induced
      teratogenesis in the hippocampus. The current study utilized a three-trimester
      rodent model of FASD to examine changes to some of the enzymatic regulators of
      the epigenome in adolescence. Combined pre- and post-natal alcohol
      exposureresulted in a significant increase in DNA methyltransferase activity
      (DNMT), without affecting histone deacetylase activity (HDAC). Developmental
      alcohol exposure also caused a change in gene expression of regulators of the
      epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2
      (MeCP2). The modifications of the activity and expression of epigenetic
      regulators in the hippocampus of rodents perinatally exposed to alcohol suggest
      that alcohol's impact on the epigenome and its regulators may be one of the
      underlying mechanisms of alcohol teratogenesis. 

PMID- 23542007
TI  - The disordered C-terminal domain of human DNA glycosylase NEIL1 contributes to
      its stability via intramolecular interactions.
AB  - NEIL1 [Nei (endonuclease VIII)-like protein 1], one of the five mammalian DNA
      glycosylases that excise oxidized DNA base lesions in the human genome to
      initiate base excision repair, contains an intrinsically disordered C-terminal
      domain (CTD; ~100 residues), not conserved in its Escherichia coli prototype Nei.
      Although dispensable for NEIL1's lesion excision and AP lyase activities, this
      segment is required for efficient in vivo enzymatic activity and may provide an
      interaction interface for many of NEIL1's interactions with other base excision
      repair proteins. Here, we show that the CTD interacts with the folded domain in
      native NEIL1 containing 389 residues. The CTD is poised for local folding in an
      ordered structure that is induced in the purified fragment by osmolytes.
      Furthermore, deletion of the disordered tail lacking both Tyr and Trp residues
      causes a red shift in NEIL1's intrinsic Trp-specific fluorescence, indicating a
      more solvent-exposed environment for the Trp residues in the truncated protein,
      which also exhibits reduced stability compared to the native enzyme. These
      observations are consistent with stabilization of the native NEIL1 structure via
      intramolecular, mostly electrostatic, interactions that were disrupted by
      mutating a positively charged (Lys-rich) cluster of residues (amino acids 355
      360) near the C-terminus. Small-angle X-ray scattering (SAXS) analysis confirms
      the flexibility and dynamic nature of NEIL1's CTD, a feature that may be critical
      to providing specificity for NEIL1's multiple, functional interactions.

PMID- 23542009
TI  - Structural basis for the recognition of Ubc13 by the Shigella flexneri effector
      OspI.
AB  - Ubc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear
      factor-kappaB signal transduction pathway in human diseases. The Shigella
      flexneri effector OspI affects inflammatory responses by catalyzing the
      deamidation of a specific glutamine residue at position 100 in Ubc13 during
      infection. This modification prevents the activation of the TNF (tumor necrosis
      factor) receptor-associated factor 6, leading to modulation of the diacylglycerol
      CBM (CARD-Bcl10-Malt1) complex-TNF receptor-associated factor 6-nuclear factor
      kappaB signaling pathway. To elucidate the structural basis of OspI function, we
      determined the crystal structures of the catalytically inert OspI C62A mutant and
      its complex with Ubc13 at resolutions of 3.0 and 2.96A, respectively. The
      structure of the OspI-Ubc13 complex revealed that the interacting surfaces
      between OspI and Ubc13 are a hydrophobic surface and a complementary charged
      surface. Furthermore, we predict that the complementary charged surface of OspI
      plays a key role in substrate specificity determination.

PMID- 23542008
TI  - Steric complementarity in the decoding center is important for tRNA selection by
      the ribosome.
AB  - Accurate tRNA selection by the ribosome is essential for the synthesis of
      functional proteins. Previous structural studies indicated that the ribosome
      distinguishes between cognate and near-cognate tRNAs by monitoring the geometry
      of the codon-anticodon helix in the decoding center using the universally
      conserved 16S ribosomal RNA bases G530, A1492 and A1493. These bases form
      hydrogen bonds with the 2'-hydroxyl groups of the codon-anticodon helix, which
      are expected to be disrupted with a near-cognate codon-anticodon helix. However,
      a recent structural study showed that G530, A1492 and A1493 form hydrogen bonds
      in a manner identical with that of both cognate and near-cognate codon-anticodon
      helices. To understand how the ribosome discriminates between cognate and near
      cognate tRNAs, we made 2'-deoxynucleotide and 2'-fluoro substituted mRNAs, which
      disrupt the hydrogen bonds between the A site codon and G530, A1492 and A1493.
      Our results show that multiple 2'-deoxynucleotide substitutions in the mRNA
      substantially inhibit tRNA selection, whereas multiple 2'-fluoro substitutions in
      the mRNA have only modest effects on tRNA selection. Furthermore, the miscoding
      antibiotics paromomycin and streptomycin rescue the defects in tRNA selection
      with the multiple 2'-deoxynucleotide substituted mRNA. These results suggest that
      steric complementarity in the decoding center is more important than the hydrogen
      bonds between the A site codon and G530, A1492 and A1493 for tRNA selection. 

PMID- 23542010
TI  - The RYMV-encoded viral suppressor of RNA silencing P1 is a zinc-binding protein
      with redox-dependent flexibility.
AB  - Viral suppressors of RNA interference (VSRs) target host gene silencing pathways,
      thereby operating important roles in the viral cycle and in host cells, in which
      they counteract host innate immune responses. However, the molecular mechanisms
      of VSRs are poorly understood. We provide here biochemical and biophysical
      features of the dual suppressor/activator VSR P1 protein encoded by the rice
      yellow mottle virus. In silico analyses of P1 suggested common features with zinc
      finger proteins and native mass spectrometry unambiguously confirmed that
      recombinant P1 binds reversibly two zinc atoms, each with a different strength.
      Additionally, we demonstrate that the reaction of P1 with H2O2 leads to zinc
      release, disulfide bond formation, and protein oligomerization. A reversible
      protein modification by redox alterations has only been described for a limited
      number of zinc finger proteins and has never been reported for VSRs. Those
      reported here for P1 might be a general feature of Cys-rich VSRs and could be a
      key regulatory mechanism for the control of RNA silencing. 

PMID- 23542011
TI  - D316 is critical for the enzymatic activity and HIV-1 restriction potential of
      human and rhesus APOBEC3B.
AB  - APOBEC3B is one of seven human APOBEC3 DNA cytosine deaminases that function to
      inhibit the replication and persistence of retroelements and retroviruses. Human
      APOBEC3B restricts the replication of HIV-1 in HEK293 cells, while our laboratory
      clone of rhesus macaque APOBEC3B did not. We mapped the restriction determinant
      to a single amino acid difference that alters enzymatic activity. Human APOBEC3B
      D316 is catalytically active and capable of restricting HIV-1 while rhesus
      APOBEC3B N316 is not; swapping these residues alters the activity and restriction
      phenotypes respectively. Genotyping of primate center rhesus macaques revealed
      uniform homozygosity for aspartate at position 316. Considering the C-to-T nature
      of the underlying mutation, we suspect that our rhesus APOBEC3B cDNA was
      inactivated by its own gene product during subcloning in Escherichia coli. This
      region has been previously characterized for its role in substrate specificity,
      but these data indicate it also has a fundamental role in deaminase activity.

PMID- 23542012
TI  - Protective effects of lithium: a new look at an old drug with potential
      antioxidative and anti-inflammatory effects in an animal model of sepsis.
AB  - Sepsis is the systemic response of an organism against microorganisms and toxins.
      Lithium is a therapeutic agent used for bipolar disorder and neurodegenerative
      disease, and it exerts pleiotropic effects on various cellular processes. The
      present study aimed to determine the effect of lithium on cecal ligation and
      puncture (CLP)-induced tissue injury in the lungs, by inhibiting the pro
      inflammatory cytokine response, and the generation of reactive oxygen species
      (ROS) triggered by polymicrobial sepsis. Five groups of 20 rats each were used:
      1) sham-operated control group; 2) CLP group; 3) 50mg/kg lithium-treated control
      healthy group; 4) 25 mg/kg lithium-treated CLP group; and 5) 50 mg/kg lithium
      treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All
      rat groups were killed 16 h later, and lung and blood samples were analyzed
      histopathologically and biochemically. The 25 and 50 mg/kg of lithium decreased
      the level of interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and the tumor
      necrosis factor-alpha (TNF-alpha) in the serum, and the 8-iso-prostaglandin
      F2alpha (8-ISO) level in lung tissue. The lithium also increased the activity of
      superoxide dismutase (SOD) and the total levels of glutathione (GSH) in the lung
      tissues of rats. The histopathological scores and examinations were in accordance
      with the biochemical results, and revealed significant differences in the
      inflammation scores between the sepsis group and the other groups. The
      CLP+lithium 50mg/kg group had the lowest inflammation score among the CLP groups.
      Our results indicated that the therapeutic administration of lithium prevented
      oxidative stress changes and cytokine changes, and also protected vital tissues.

PMID- 23542013
TI  - Carbon partitioning in photosynthesis.
AB  - The work seeks to raise awareness of a fundamental problem that impacts the
      renewable generation of fuels and chemicals via (photo)synthetic biology. At
      issue is regulation of the endogenous cellular carbon partitioning between
      different biosynthetic pathways, over which the living cell exerts stringent
      control. The regulation of carbon partitioning in photosynthesis is not
      understood. In plants, microalgae and cyanobacteria, methods need be devised to
      alter photosynthetic carbon partitioning between the sugar, terpenoid, and fatty
      acid biosynthetic pathways, to lower the prevalence of sugar biosynthesis and
      correspondingly upregulate terpenoid and fatty acid hydrocarbons production in
      the cell. Insight from unusual but naturally occurring carbon-partitioning
      processes can help in the design of blueprints for improved photosynthetic fuels
      and chemicals production.

PMID- 23542014
TI  - Role of phosphatidylinositol 5-phosphate 4-kinase alpha in zebrafish development.
AB  - Phosphatidylinositol 5-phosphate 4-kinases (PIP4Ks) phosphorylate
      phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5
      bisphosphate; their most likely function is the regulation of the levels of PI5P,
      a putative signalling intermediate. There are three mammalian PIP4Ks isoforms
      (alpha, beta and gamma), but their physiological roles remain poorly understood.
      In the present study, we identified the zebrafish orthologue (zPIP4Kalpha) of the
      high-activity human PIP4K alpha isoform and analyzed its role in embryonic
      development. RT-PCR analysis and whole-mount in situ hybridization experiments
      showed that zPIP4Kalpha is maternally expressed. At later embryonic stages, high
      PIP4Kalpha expression was detected in the head and the pectoral fins. Knockdown
      of zPIP4Kalpha by antisense morpholino oligonucleotides led to severe
      morphological abnormalities, including midbody winding defects at 48hpf. The
      abnormal phenotype could be rescued, at least in large part, by injection of
      human PIP4Kalpha mRNA. Our results reveal a key role for PIP4Kalpha and its
      activity in vertebrate tissue homeostasis and organ development.

PMID- 23542015
TI  - Leukocyte integrins alphaLbeta2, alphaMbeta2 and alphaXbeta2 as collagen
      receptors--receptor activation and recognition of GFOGER motif.
AB  - Integrins alphaLbeta2, alphaMbeta2 and alphaXbeta2 are expressed on leukocytes.
      Their primary ligands are counter transmembrane receptors or plasma proteins,
      such as intercellular cell adhesion molecule-1 (ICAM-1) or components of
      complement system (iC3b, iC4b), respectively. Function blocking antibodies for
      these integrins may also reduce cell adhesion to collagens. To make the first
      systematical comparison of human alpha(L)beta2, alpha(M)beta2 and alpha(X)beta2
      as collagen receptors, we produced the corresponding integrin alphaI domains both
      in wild-type and activated form and measured their binding to collagens I-VI. In
      the "closed" (wild-type) conformation, the alpha(L)I and alpha(M)I domains bound
      with low avidity to their primary ligands, and the interaction with collagens was
      also very weak. Gain-of-function mutations alpha(L) I306G, alpha(L) K287C/K294C
      and alpha(M) I316G are considered to mimic "open", activated alphaI domains. The
      binding of these activated alphaI domains to the primary ligands was clearly
      stronger and they also recognized collagens with moderate avidity (K(d)400 nM).
      After activation, the alphaLI domain favored collagen I (K(d )~ 80 nM) when
      compared to collagen IV. The integrin alphaXI domain acted in a very different
      manner since already in native, wild-type form it bound to collagen IV and iC3b
      (K(d) ~ 200-400 nM). Antibodies against alphaXbeta2 and alphaMbeta2 blocked
      promyelocytic leukemia cell adhesion to the collagenous GFOGER motif, a binding
      site for the beta1 integrin containing collagen receptors. In brief, leukocyte
      beta2 integrins may act as collagen receptors in a heterodimer specific manner.

PMID- 23542016
TI  - Hepatitis B virus core protein enhances human telomerase reverse transcriptase
      expression and hepatocellular carcinoma cell proliferation in a c-Ets2-dependent
      manner.
AB  - Hepatitis B virus core protein can regulate viral replication and host gene
      expression. However, it is unclear whether and how hepatitis B virus core protein
      regulates hepatocellular carcinoma cell proliferation. Induction of hepatitis B
      virus core protein over-expression significantly enhanced the proliferation of
      hepatocellular carcinoma cells, while knockdown of hepatitis B virus core protein
      expression inhibited the proliferation of hepatocellular carcinoma cells. Altered
      hepatitis B virus core protein expression significantly changed the growth of
      implanted hepatocellular carcinoma in vivo. Microarray analysis indicated that
      hepatitis B virus core protein up-regulated human telomerase reverse
      transcriptase expression, which was further validated by over-expression and
      knockdown assays in vitro. Furthermore, knockdown of human telomerase reverse
      transcriptase expression mitigated the hepatitis B virus core protein-enhanced
      hepatocellular carcinoma cell proliferation and clone formation in vitro.
      Luciferase assays indicated that hepatitis B virus core protein enhanced the
      promoter activity of human telomerase reverse transcriptase, which was dependent
      on the binding of c-Ets2 to the promoter region between -192 and -187. In
      addition, hepatitis B virus core protein enhanced human telomerase reverse
      transcriptase transcription in HepG2 cells, but not in the c-Ets2-silencing HepG2
      cells. Moreover, hepatitis B virus core protein promoted c-Ets2 nuclear
      translocation. Finally, significantly higher levels of human telomerase reverse
      transcriptase expression and nuclear c-Ets2 accumulation were detected in
      hepatitis B virus core protein-positive hepatocellular carcinoma samples. Our
      findings demonstrate that hepatitis B virus core protein promotes hepatocellular
      carcinoma cell proliferation by up-regulating the c-Ets2-dependent expression of
      human telomerase reverse transcriptase.

PMID- 23542017
TI  - Dietary crystalline common-, micro-, nanoscale and emulsified nanoscale
      sitosterol reduce equally the cholesterol pool in guinea pigs, but varying
      nanosystems result in different sterol concentrations in serosal jejunum.
AB  - Due to hypocholesterolemic effects, sitosterol is used in functional foods and
      nanoscale dispersions. To investigate the influence of dietary sitosterol on
      sterol concentrations in Dunkin Hartley guinea pigs, seven groups consisting of
      eight animals each were fed either a basal diet (BD), a high-cholesterol diet
      (HC) or a high-cholesterol diet supplemented with crystalline commonscale (CCS),
      microscale (CMS, low-dosed: CMLS), nanoscale (CNS) or emulsified nanoscale (ENS)
      sitosterol. When compared to HC group, all sitosterol formulations decreased
      liver cholesterol concentrations. No differences in cholesterol or sitosterol
      concentration were found in plasma and liver between CCS, CMS, CNS, and ENS
      groups. Apparent cholesterol digestibility decreased by increasing crystalline
      microscale sitosterol doses. Despite a lower sitosterol intake, ENS group had
      higher serosal sitosterol concentrations in jejunum than CNS group. To elucidate
      an impact of the sitosterol nanosystem on gut tissues further studies are
      necessary. FROM THE CLINICAL EDITOR: In this study, the use of sitosterols in a
      rat model led to contradicting conclusions regarding their ability to reduce
      cholesterol levels efficiently in guinea pigs, suggesting that more preclinical
      data is needed before this method could become applicable to human studies.

PMID- 23542018
TI  - Single low-dose un-adjuvanted HBsAg nanoparticle vaccine elicits robust, durable
      immunity.
AB  - Chitosan nanoparticles were evaluated as a vaccine delivery system for hepatitis
      B surface antigen (HBsAg) in the absence of adjuvant. Nano-encapsulated HBsAg
      (HBsAg chitosan-NP) was endocytosed more rapidly and efficiently by dendritic
      cells compared to soluble HBsAg. FRET analysis demonstrated that intact
      nanoparticles were taken up by DCs. To determine the immunogenicity of adjuvant
      free nano-encapsulated HBsAg, mice were immunized with a single dose of non
      encapsulated HBsAg, HBsAg chitosan-NP, or HBsAg alum. Mice immunized with
      adjuvant-free nanoparticle elicited anti-HBs antibodies at significantly higher
      titers compared to mice immunized with HBsAg alum. Elevated numbers of BAFF-R(+)
      B cells and CD138+ plasma cells account for the heightened anti-HBs response in
      nanoparticle immunized mice. Increases in Tfh cells provide a mechanism for the
      accumulation of anti-HBs secreting cells. Thus, chitosan nanoparticle vaccines
      represent a promising un-adjuvanted platform to generate robust and durable
      immunity to HBsAg and other subunit antigens following a single low-dose
      administration. FROM THE CLINICAL EDITOR: In this study, chitosan nanoparticle
      vaccines are demonstrated as a promising un-adjuvanted platform to generate
      robust and durable immunity to HBsAg and other subunit antigens following a
      single low-dose administration in a murine model. The authors also demonstrated
      superior antibody response induction compared with non-encapsulated HBs antigen
      and HBsAg aluminum.

PMID- 23542019
TI  - A new axiomatic approach to the evaluation of population health.
AB  - In this paper we explore the implications of normative principles for the
      evaluation of population health. We formalize those principles as axioms for
      social preferences over distributions of health for a given population. We single
      out several focal population health evaluation functions, which represent social
      preferences, as a result of combinations of those axioms. Our results provide new
      rationale for popular theories in health economics, such as the unweighted
      aggregation of quality-adjusted life years (QALYs) or healthy years equivalents
      (HYEs) and generalizations of the two, aimed to capture concerns for distributive
      justice, without resorting to controversial assumptions on individual
      preferences.

PMID- 23542020
TI  - Does retirement age impact mortality?
AB  - The relationship between retirement and mortality is studied with a unique
      administrative data set covering the full population of Norway. A series of
      retirement policy changes in Norway reduced the retirement age for a group of
      workers but not for others. Difference-in-differences estimation based on monthly
      birth cohorts and treatment group status show that the early retirement programme
      significantly reduced the retirement age; this holds true also when we account
      for programme substitution, for example into the disability pension. Instrumental
      variables estimation results show no effect on mortality of retirement age;
      neither do estimation results from a hazard rate model.

PMID- 23542021
TI  - A survey of diagnostic radiology residency program directors and the increasing
      demands of program leadership.
AB  - PURPOSE: The aim of this study was to identify trends and opinions with respect
      to leadership turnover, leadership responsibilities, and residency requirements.
      METHODS: Program directors (PDs) of diagnostic radiology (DR) residency programs
      were identified via the ACGME and the Fellowship and Residency Electronic
      Interactive Database, along with a programmatic website search. A web-based
      survey was e-mailed, with questions concerning lengths of time the current and
      prior PDs held their positions, residency size, amounts of time spent on and
      lengths of current and past Program Information Forms, and opinions on how the
      position has changed and how metrics, outcomes, and documentation may be
      affecting teaching, resident education, and patient care. RESULTS: Thirty-two
      percent (60 of 186) of US DR residency PDs answered at least 1 of the survey
      questions. The average length of time the current PDs held their positions was
      shorter compared with the previous PDs, and it has taken longer and required more
      pages to complete the current Program Information Forms compared with prior
      cycles. The majority of respondents felt that the job of PD was harder than 5
      years ago and that turnover among PDs is a "current/impending" problem. The
      majority of respondents felt that time spent on metrics, outcomes, and
      documentation is taking away from teaching, learning, and taking care of
      patients. CONCLUSIONS: Many DR residency PDs have recognized increased
      administrative burdens in recent years. Some feel that these increased demands
      may in part have negative effects on resident education and patient care.

PMID- 23542022
TI  - Ways to improve radiologists' adherence to Fleischner Society guidelines for
      management of pulmonary nodules.
AB  - PURPOSE: The aim of this study was to assess one institution's experience with
      radiologists' adherence to the Fleischner Society guidelines for managing
      pulmonary nodules incidentally detected on CT, which anecdotally was
      substantially higher than in a recent report. METHODS: All chest and abdominal CT
      scans in the electronic messaging system for communicating unexpected abnormal
      imaging findings to referring physicians were searched for the terms "lung" or
      "pulmonary" and "nodule" or "mass." Data were collected regarding patient age,
      nodule size, and whether the patient was at high risk for malignancy (primarily
      smoking history) or had evidence of prior or concurrent malignancy. Radiologists'
      recommendations were then correlated with the Fleischner guidelines for nodule
      size and patient history. RESULTS: Of the study cohort of 1,412 patients who
      underwent chest and abdominal CT scans, 420 had new pulmonary nodules. Of these,
      205 (48.8%) were excluded because of prior or concurrent malignancies, nodules
      initially seen on prior CT examinations, ground-glass appearance, or age <40
      years. In the remaining 215 patients, the radiologists' recommendations were
      consistent with the Fleischner guidelines in 82.8%. CONCLUSIONS: Radiologists'
      recommendations for the management of pulmonary nodules incidentally detected on
      CT adhered to the Fleischner guidelines in 82.8% of cases, more than twice that
      in a recent report. This difference may reflect various practical departmental
      attempts to emphasize the importance of the Fleischner guidelines in reducing
      patient radiation and health care costs.

PMID- 23542023
TI  - The recent reversal of the growth trend in MRI: a harbinger of the future?
AB  - PURPOSE: Diagnostic imaging services have been repeatedly targeted as a source of
      excess health care expenditure. In particular, MRI is considered a high-tech and
      high-cost imaging service that saw rapid increases in utilization in the early
      2000s. However, the most recent trends in the utilization of MR are not known.
      The aim of this study was to quantify trends in MR utilization overall and by
      body system from 1998 to 2010 in the Medicare population. METHODS: Medicare Part
      B data sets were obtained for 1998 to 2010 for all MR examinations performed in
      the Medicare population. Using Current Procedural Terminology codes, the total
      volume and utilization rates of all MR examinations were tabulated for each year
      of the study period. MR volume was then categorized by body system. RESULTS: The
      utilization rate of MR examinations in the Medicare population was 73 per 1,000
      beneficiaries in 1998, increased to a peak of 189 in 2008, and decreased to 183
      in 2010. The compound annual growth rate from 1998 to 2008 was 10%. The
      utilization rate in 2010 represents a decrease of 3.1% from the 2009 utilization
      rate. The most frequently imaged body section in every year was the head, which
      accounted for 2,404,250 examinations in 2010, 37.3% of all MR examinations in
      that year. CONCLUSIONS: The overall MRI utilization rate sharply increased from
      1998 until 2008 but then decreased in each of the next 2 years. A similar trend
      was noted for MR examinations performed in most body sections. These trends are
      likely to be the result of a number of possible causative factors.

PMID- 23542024
TI  - Compendium of resources for radiation safety in medical imaging using ionizing
      radiation.
AB  - PURPOSE: Diagnostic imaging, including ionizing radiation modalities, maintains a
      prominent role in the medical evaluation of patients. There is increasing
      awareness and need for information across varied sectors about low-level
      radiation and potential risks. Many medical and scientific organizations have
      resources discussing radiation risk and management. However, there is no single
      resource compiling this information. METHODS: Websites, including those of
      national and international medical organizations, were reviewed for information
      on radiation dose, risk, justification, optimization, guidelines (including
      general information about improvement in quality and dose reduction without
      specific mention of optimization techniques), appropriateness criteria, and
      general principles of radiation safety for CT, fluoroscopy or angiography, and
      radiography. This information was organized into 8 tables, categorized by
      modality, and separated for adult and pediatric populations. Websites with
      training modules were noted as well. RESULTS: Twenty-nine websites were explored.
      Overall, less information is available about medical radiation safety in children
      compared with adults. Across both groups, most information is available on CT,
      then fluoroscopy, and finally radiography. Across all groups and modalities,
      there is no information available for patients or parents on optimization,
      appropriateness, or guidelines, with the exception of adult radiography, for
      which there are some guidelines. CONCLUSIONS: This compendium serves as a
      collective resource for communities including the public and regulatory
      organizations. Additionally, the compendium can be used to determine redundant or
      deficient areas, providing opportunities for more comprehensive resources and
      efficient efforts in accessing medical radiation patient safety information.

PMID- 23542026
TI  - Last orders, please!

PMID- 23542027
TI  - ACR Appropriateness Criteria chronic chest pain-low to intermediate probability
      of coronary artery disease.
AB  - Chronic chest pain can arise from a variety of etiologies. However, of those
      potential causes, the most life-threatening include cardiac disease. Chronic
      cardiac chest pain may be caused either by ischemia or atherosclerotic coronary
      artery disease or by other cardiac-related etiologies, such as pericardial
      disease. To consider in patients, especially those who are at low risk for
      coronary artery disease, are etiologies of chronic noncardiac chest pain.
      Noncardiac chest pain is most commonly related to gastroesophageal reflux disease
      or other esophageal diseases. Alternatively, it may be related to
      costochondritis, arthritic or degenerative diseases, old trauma, primary or
      metastatic tumors, or pleural disease. Rarely, noncardiac chest pain may be
      referred pain from organ systems below the diaphragm, such as the gallbladder.
      The ACR Appropriateness Criteria are evidence-based guidelines for specific
      clinical conditions that are reviewed every 2 years by a multidisciplinary expert
      panel. The guideline development and review include an extensive analysis of
      current medical literature from peer-reviewed journals and the application of a
      well-established consensus methodology (modified Delphi) to rate the
      appropriateness of imaging and treatment procedures by the panel. In those
      instances in which evidence is lacking or not definitive, expert opinion may be
      used to recommend imaging or treatment.

PMID- 23542028
TI  - Point: The New England Journal of Medicine article suggesting overdiagnosis from
      mammography screening is scientifically incorrect and should be withdrawn.

PMID- 23542029
TI  - The eye of the beholder.

PMID- 23542031
TI  - Counterpoint: The New England Journal of Medicine article suggesting
      overdiagnosis from mammography screening is scientifically correct and should not
      be withdrawn.

PMID- 23542032
TI  - Protective role of the endoplasmic reticulum protein mitsugumin23 against
      ultraviolet C-induced cell death.
AB  - The endoplasmic reticulum (ER) operates in adaptive responses to various
      stresses, dictating cell fate. Here we show that knockdown of the ER protein
      mitsugumin23 (MG23) enhances cell death induced by ultraviolet C (UVC), which
      causes DNA damage. The small heat shock protein alphaB-crystallin (alphaBC) is
      identified as a MG23 binding molecule and its knockdown facilitates death of UVC
      exposed cells. Conversely, alphaBC lowered UVC sensitivity when expressed as an
      ER-anchored form. Taken together, the results suggest that MG23 plays a
      protective role against UVC by accumulating alphaBC in the close vicinity of the
      ER.

PMID- 23542033
TI  - Effects of Rbp3 on lipid peroxidation and salt tolerance in Synechocystis sp. PCC
      6803.
AB  - RNA-binding proteins (Rbps) are involved in many post-transcriptional regulation
      processes. As previously shown, inactivation of rbp3 in Synechocystis sp. PCC
      6803 significantly decreased the stability of acyl-lipid desaturase (des) mRNAs
      and the degree of unsaturation of membrane lipids. In comparison to the wild
      type, the rbp3 mutant produced less lipid peroxides under cold stress and showed
      greater inhibition of photosynthesis/respiration activities by salt stress.
      Overexpression of desA partially restored levels of lipid peroxidation and salt
      tolerance in the mutant. Effects of Rbp3 on lipid peroxidation and salt tolerance
      appears to be directly related to the change of degree of lipid unsaturation.

PMID- 23542034
TI  - Transient receptor potential vanilloid-2 mediates the effects of transient heat
      shock on endocytosis of human monocyte-derived dendritic cells.
AB  - Our goal was to investigate the effect of heat shock on human monocyte-derived
      dendritic cells (DCs) and to dissect the role of thermosensitive transient
      receptor potential (TRP) channels in the process. We provide evidence that a
      short heat shock challenge (43  degrees C) decreased the endocytotic activity of
      the DCs and that this effect could be alleviated by the RNAi-mediated knockdown
      of TRPV2 but, importantly, not by the pharmacological (antagonists) or molecular
      (RNAi) suppression of TRPV1 and TRPV4 activities/levels. Likewise, the heat shock
      induced robust membrane currents were selectively and markedly inhibited by TRPV2
      "silencing" whereas modulation of TRPV1 and TRPV4 activities, again, had no
      effect. These intriguing data introduce TRPV2-coupled signaling as a key player
      in mediating the cellular actions of heat shock on DCs.

PMID- 23542035
TI  - IFNbeta autocrine feedback is required to sustain TLR induced production of MCP-1
      in macrophages.
AB  - Chemokines, including MCP-1, are crucial to mounting an effective immune response
      due to their ability to recruit other immune cells. We show that sustained LPS or
      poly(I:C)-stimulated MCP-1 production requires an IFNbeta-mediated feedback loop.
      Consistent with this, exogenous IFNbeta was able to induce MCP-1 transcription in
      the absence of other stimuli. Blocking IFNbeta signaling with Ruxolitinib, a JAK
      inhibitor, inhibited MCP-1 transcription. The MCP-1 promoter contains potential
      STAT binding sites and we demonstrate that STAT1 is recruited upon IFNbeta
      stimulation. Furthermore we find that IL-10 knockout increases MCP-1 production
      in response to LPS, which may reflect an ability of IL-10 to repress IFNbeta
      production. Overall, these results show the importance of the balance between
      IFNbeta and IL-10 in the regulation of MCP-1.

PMID- 23542036
TI  - Regulation of the MDR1 promoter by E2F1 and EAPP.
AB  - Multidrug resistance (MDR), one of the main reasons for diminishing efficacy of
      prolonged chemotherapy, is frequently caused by the elevated expression of the
      ABCB1/MDR1 gene encoding PGP (P-glycoprotein). EAPP (E2F Associated
      PhosphoProtein) is a frequently overexpressed protein in human tumor cells. It
      inhibits apoptosis in a p21-dependent manner. We show here that EAPP stimulates
      the MDR1 promoter resulting in higher PGP levels. Independently of EAPP, E2F1
      also increases the activity of the MDR1 promoter. Co-expression of pRb inhibits
      E2F1-, but not EAPP-dependent promoter activation. The upregulation of PGP might
      contribute to the survival of tumor cells during chemotherapy and worsen the
      prognosis for the patient.

PMID- 23542037
TI  - HDAC inhibitors prevent the induction of the immediate-early gene FOSL1, but do
      not alter the nucleosome response.
AB  - Dynamic histone acetylation, catalyzed by lysine acetyltransferases and HDACs, is
      critical to IEG expression. Expression of IEGs, such as FOSL1, is induced by
      several signal transduction pathways resulting in activation of the protein
      kinase MSK and phosphorylation of histone H3 at serine 10 of nucleosomes (the
      nucleosome response) at the upstream promoter and regulatory region of target
      genes. HDAC inhibitors prevent FOSL1 gene induction and the association of HDAC1,
      2 and 3 with the gene body. However, HDAC inhibitors did not prevent the
      nucleosome response. Thus HDAC inhibitors perturb events downstream of the
      nucleosome response required for FOSL1 transcription initiation.

PMID- 23542038
TI  - Impact of a productivity-based compensation system on faculty clinical teaching
      scores, as evaluated by anesthesiology residents.
AB  - STUDY OBJECTIVE: To determine whether financial incentives given to faculty
      members for favorable teaching scores improve the quality of clinical education.
      DESIGN: Retrospective analysis. SETTING: Large U.S. academic anesthesiology
      department. STUDY SUBJECTS: 61 academic and 72 clinical faculty members.
      MEASUREMENTS: Since, academic year (AY) 2004, as part of a comprehensive clinical
      and academic productivity-based compensation system, academic faculty members
      receiving higher operating room (OR) teaching evaluation scores from the
      residents have been rewarded financially. Clinical Faculty members also have been
      rated, but have not received incentives based on scores. Annual averaged OR
      teaching scores of each faculty member on a 0-9 scale, where 9 = best, were
      gathered anonymously with faculty classification (academic or clinical). Average
      overall scores and percentage of faculty with each score category (8.51-9.00,
      8.01-8.50, 7.00-8.00, or <7.00) were compared between the pre-implementation
      (AY2002-AY2003) and post-implementation (AY2004-AY2005) periods. Scores between
      the academic and clinical faculty also were compared. MAIN RESULTS: No
      significant difference was noted in the average scores between the pre
      implementation and post-implementation periods in a paired comparison (academic:
      7.83 +/- 0.48 vs 7.85 +/- 0.50, P = 0.61; clinical: 7.54 +/- 0.75 vs 7.66 +/-
      0.60, P = 0.21). No statistically significant change was noted in the composition
      of score categories in the academic (P = 0.63) or clinical faculty (P = 0.20)
      members. Overall, the academic faculty received significantly higher scores than
      the clinical faculty (7.84 +/- 0.49 vs 7.60 +/- 0.67, P = 0.0003). CONCLUSIONS: A
      productivity-based faculty compensation system did not appear to influence
      faculty OR teaching scores.

PMID- 23542039
TI  - The in vitro cytotoxicity and genotoxicity of cigarette smoke particulate matter
      with reduced toxicant yields.
AB  - Tobacco smoke contains more than 5600 constituents, of which approximately 150
      are toxicants. This paper describes the activities in the Neutral Red uptake
      (NRU) assay, the Salmonella mutagenicity test (SAL), the mouse lymphoma mammalian
      cell mutation assay (MLA) and the in vitro micronucleus test (IVMNT) of
      Particulate Matter (PM) obtained from experimental cigarettes (ECs), designed to
      produce reduced levels of toxicants. The designs included tobacco substitute
      sheet (TSS) containing glycerol, which dilutes toxicants in smoke, or the
      incorporation of blend-treated (BT) tobacco to reduce the levels of nitrogenous
      toxicant precursors and some polyphenols. All samples were cytotoxic in the NRU,
      however TSS reduced PM cytotoxicity in this assay. All PMs were mutagenic in the
      SAL, MLA and IVMNT. Reductions in bacterial mutagenicity were observed in the
      SAL, for cigarettes with BT tobacco, compared with their respective controls. The
      quantitative changes in bacterial mutagenicity could be explained by analytical
      chemistry data on smoke generated from the ECs used in the study. These
      observations, and the absence of consistent qualitative differences in the
      activities of the experimental, control and reference cigarettes, suggest that
      reduced toxicity cigarettes, as measured by the tests described in this paper,
      may be developed without introducing any additional cytotoxic or genotoxic
      hazards, but the impact of this on human health risks remains unknown.

PMID- 23542040
TI  - Anti-inflammatory and antioxidant properties of hydroalcoholic crude extract from
      Casearia sylvestris Sw. (Salicaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris Sw. is widely used in popular
      medicine to treat inflammatory conditions. AIM OF THE STUDY: To investigate the
      anti-inflammatory and antioxidant properties of hydroalcoholic crude extract
      (HCE) taken from Casearia sylvestris Sw. (Salicaceae). METHODS AND RESULTS: The
      effect of the HCE from this plant (3-300 mg/kg) on the reduction of inflammatory
      response to carrageenan was investigated in pleurisy in rats (intrapleural, 2% in
      0.2 mL) or paw edema in mice (intraplantar, 300 MUg/20 MUL, right hind paw). The
      plant anti-inflammatory action was assessed by its capability in inhibiting cell
      migration, enzymatic activity of myeloperoxidase (MPO) and production of
      nitrite/nitrate or edema. The in vitro antioxidant activity of this extract
      against lipid peroxidation and damage to proteins was assessed as possible
      pathways to contribute as anti-inflammatory mechanisms. Carrageenan-induced hind
      paw edema (739.3 +/- 11.9 MUm) was reduced by HCE (30 mg/kg: 462.8 +/- 28.38 MUm)
      to similar extents as dexametasone (365.1 +/- 16.7). In pleurisy, treatment of
      the animals with HCE (100mg/kg: 0.010 +/- 0.001 mU/mg of protein) also reduced
      MPO activity augmented by carrageenan (0.020 +/- 0.001 mU/mg of protein) as well
      as leukocytes migration (carrageenan: 17.8890 +/- 2.3900 leukocytes/mL, HCE
      100mg/kg: 7.0880 +/- 9631 leukocytes/mL). Significant effects were also observed
      in animals treated with different doses of HCE in biochemical tests for oxidative
      stress analysis. CONCLUSION: The anti-inflammatory and antioxidant effects of HCE
      from Casearia sylvestris Sw. suggests a potential therapeutic benefit of this
      plant in treatment of inflammatory conditions.

PMID- 23542041
TI  - In vivo and in vitro anti-inflammatory activity of Lentinus polychrous extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lentinus polychrous is a Thai local edible
      mushroom, traditionally used for the treatments of fever and inflammation due to
      snake or scorpion envenomation. AIM OF STUDY: The present study aimed to
      investigate an anti-inflammatory effect of Lentinus polychrous mycelial extract
      (LPME) both in vitro and in vivo. MATERIALS AND METHODS: The cytotoxicity and
      suppressive effects of LPME on nitric oxide production, intracellular O2(-)
      production, pro-inflammatory mediator expression, TNF-alpha production were
      determined by using LPS-activated RAW 264.7 cells. In addition, Anti-inflammatory
      effect of LPME was evaluated by using carageenan-induced paw edema in rats.
      RESULTS: The LPME exhibited cytotoxicity with 50% inhibitory concentration (IC50)
      of 280.25 +/- 10.10 MUg/ml and significantly suppressed the productions of NO and
      intracellular O2(-) with dose-dependent manner. LPME decreased the expressions of
      iNOS, IL-1beta, IL-6, TNF-alpha and COX-2 and significantly decreased the TNF
      alpha production in LPS-activated macrophage with dose-dependent manners.
      Moreover, LPME showed significant suppressive effect on paw edema in rats.
      CONCLUSION: The results clearly revealed that the LPME inhibited NO and pro
      inflammatory productions by down-regulating the gene expressions of pro
      inflammatory mediators leading to the decrease paw edema in rat which support the
      traditional use.

PMID- 23542042
TI  - Co-oscillation and synchronization between the posterior thalamus and the caudate
      nucleus during visual stimulation.
AB  - Recent results suggest significant cross-correlation between the spike trains of
      the suprageniculate nucleus (SG) of the posterior thalamus and the caudate
      nucleus (CN) during visual stimulation. In the present study visually evoked
      local field potentials (LFPs) were recorded simultaneously in the CN and the SG
      in order to investigate the coupling between these structures at a population
      level. The effect of static and dynamic visual stimulation was analyzed in 55 SG
      CN LFP pairs in the frequency range 5-57Hz. Statistical analysis revealed
      significant correlation of the relative powers of each investigated frequency
      band (5-8Hz, 8-12Hz, 12-35Hz and 35-57Hz) during both static and dynamic visual
      stimulation. The temporal evolution of cross-correlation showed that in the
      majority of the cases the SG was activated first, and in approximately one third
      of the cases, the CN was activated earlier. These observations suggest a
      bidirectional information flow. The most interesting finding of this study is
      that different frequency bands exhibited significant cross-correlation in a
      stimulation paradigm-dependent manner. That is, static stimulation usually
      increased the cross-correlation of the higher frequency components (12-57Hz) of
      the LFP, while dynamic stimulation induced changes in the lowest frequency band
      (5-8Hz). This suggests a parallel processing of dynamic and static visual
      information in the SG and the CN. To our knowledge we are the first to provide
      evidence on the co-oscillation and synchronization of the CN and the SG at a
      population level upon visual stimulation, which suggests a significant
      cooperation between these structures in visual information processing.

PMID- 23542043
TI  - Effects of medullary lesions on conditional pacemaker activity of neonatal rat
      hypoglossal motoneurons in vitro.
AB  - N-methyl-D-aspartate (NMDA) has been demonstrated to induce rhythmic activity in
      various neurons, including hypoglossal motoneurons (XIIms) and converts them to
      conditional pacemakers. Using whole-cell patch clamp recording in a slice
      preparation from neonatal rats, we confirmed that some XIIms act as conditional
      pacemakers, with TTX-insensitivity and a burst period that is voltage-dependent
      during NMDA application. Other XIIms in this study only fired tonically with NMDA
      application. Effects of medullary structures on conditional pacemaker XIIms were
      assessed using lesioned preparations. As a result, NMDA-induced rhythm (NIR) in
      the XIIm was observed with ventral lesions (excluding inspiratory neurons) and
      with dorsal lesions (excluding the swallowing center located in the nucleus of
      the solitary tract). The NIR was also observed with lateral lesions, but with a
      significantly decreased burst period. These data suggest that NMDA receptor
      activation selects a subset of XIIms and changes them to pacemakers whose
      properties can be altered by their excitability. The data also demonstrate that
      structures fundamental to the NIR are located within the area near the XII
      nucleus, indicating that the NIR is distinct from inspiratory and swallowing
      activities. The lateral medulla is considered to be a source of modulation of the
      excitability of XIIms.

PMID- 23542044
TI  - Weaning from mechanical ventilation in paediatrics. State of the art.
AB  - Weaning from mechanical ventilation is one of the greatest volume and strength
      issues in evidence-based medicine in critically ill adults. In these patients,
      weaning protocols and daily interruption of sedation have been implemented,
      reducing the duration of mechanical ventilation and associated morbidity. In
      paediatrics, the information reported is less consistent, so that as yet there
      are no reliable criteria for weaning and extubation in this patient group.
      Several indices have been developed to predict the outcome of weaning. However,
      these have failed to replace clinical judgement, although some additional
      measurements could facilitate this decision. 

PMID- 23542045
TI  - Giant functioning mediastinal parathyroid cyst: an unusual cause of exertional
      dyspnea and mild dysphagia.

PMID- 23542046
TI  - Prevalence of venous thromboembolism in elective thoracic surgery.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of venous
      thromboembolism (VTE) after elective thoracic surgery in patients receiving
      antithrombotic prophylaxis, and to evaluate the risk of pulmonary embolism (PE)
      after lung resection. PATIENTS AND METHOD: A descriptive, cross-sectional,
      retrospective study was designed. A total of 6004 patients were included. All
      patients underwent elective thoracic surgery. Prophylactic antithrombotic therapy
      was standardised in all cases. Patients were divided into four groups (low,
      moderate, high and very high) according to their thrombotic risk. The prevalence
      of VTE, deep vein thrombosis and PE in each group was calculated. The odds of PE
      for pneumonectomy was also calculated and compared to lobectomy. RESULTS: Eleven
      patients (0.18%) had postoperative VTE. The mean age of this subset was 65.95
      years; 90.9% were diagnosed with malignant neoplasm. Some 80.8% of patients in
      the series and all VTE cases were included in the high risk VTE group. VTE was
      more common in pneumonectomy (45.45% of VTE cases, odds ratio 4.6 compared to
      lobectomy). CONCLUSIONS: The prevalence of VTE in this series was 0.18% (1.31% in
      pneumonectomy patients). These figures could serve as reference values for
      thromboembolic disease in general thoracic surgery.

PMID- 23542047
TI  - The national lung screening trial. A before and after in lung cancer screening
      with low-dose computed tomography.

PMID- 23542048
TI  - Possible ecosystem impacts of applying maximum sustainable yield policy in food
      chain models.
AB  - This paper describes the possible impacts of maximum sustainable yield (MSY) and
      maximum sustainable total yield (MSTY) policy in ecosystems. In general it is
      observed that exploitation at MSY (of single species) or MSTY (of multispecies)
      level may cause the extinction of several species. In particular, for traditional
      prey-predator system, fishing under combined harvesting effort at MSTY (if it
      exists) level may be a sustainable policy, but if MSTY does not exist then it is
      due to the extinction of the predator species only. In generalist prey-predator
      system, harvesting of any one of the species at MSY level is always a sustainable
      policy, but harvesting of both the species at MSTY level may or may not be a
      sustainable policy. In addition, we have also investigated the MSY and MSTY
      policy in a traditional tri-trophic and four trophic food chain models.

PMID- 23542049
TI  - Competition for benefits can promote the persistence of mutualistic interactions.
AB  - Mutualistic interactions are characterized by positive density-dependence that
      should cause interacting species to go extinct when rare. However, data show
      mutualistic interactions to be common and persistent. Previous theory predicts
      persistence provided that mutualistic species are regulated by factors external
      to the mutualistic interaction (e.g., limiting background resources). Empirical
      data suggest that competition for the benefits provided by mutualistic partners
      could be a source of negative density-dependence that allows for population
      regulation, but there is little, if any, theoretical exploration of this
      mechanism. Here we develop mathematical models to investigate whether competition
      for benefits alone can allow the persistence of obligate mutualistic
      interactions. We consider the role of trade-offs in persistence, specifically,
      trade-offs between benefits acquired versus given and between competition for
      access to partners (competitive ability) and benefit acquisition. We find that
      competition for benefits alone is sufficient to promote the persistence of
      pairwise interactions and the assembly of a three-species community module from
      an initially pairwise interaction. We find that a trade-off between benefits
      acquired versus given reduces opportunities for cheating (because a species that
      acquires significantly more benefits than it gives drives its partner extinct),
      while a trade-off between competitive ability and benefit acquisition facilitates
      persistence when it is weak, but constrains persistence when it is strong. When
      both trade-offs operate simultaneously, persistence requires that each species
      acquire sufficient benefits to avoid being cheated by its partners, but not so
      much that it loses its competitive ability. The key finding is that competition
      for benefits provides a biologically-realistic mechanism for the long-term
      persistence of mutualistic interactions and the assembly of complex community
      modules from initially pairwise interactions.

PMID- 23542050
TI  - The utility of artificially evolved sequences in protein threading and fold
      recognition.
AB  - Template-based protein structure prediction plays an important role in Functional
      Genomics by providing structural models of gene products, which can be utilized
      by structure-based approaches to function inference. From a systems level
      perspective, the high structural coverage of gene products in a given organism is
      critical. Despite continuous efforts towards the development of more sensitive
      threading approaches, confident structural models cannot be constructed for a
      considerable fraction of proteins due to difficulties in recognizing low-sequence
      identity templates with a similar fold to the target. Here we introduce a new
      modeling stratagem, which employs a library of synthetic sequences to improve
      template ranking in fold recognition by sequence profile-based methods. We
      developed a new method for the optimization of generic protein-like amino acid
      sequences to stabilize the respective structures using a combined empirical
      scoring function, which is compatible with these commonly used in protein
      threading and fold recognition. We show that the artificially evolved sequences,
      whose average sequence identity to the wild-type sequences is as low as 13.8%,
      have significant capabilities to recognize the correct structures. Importantly,
      the quality of the corresponding threading alignments is comparable to these
      constructed using conventional wild-type approaches (the average TM-score is 0.48
      and 0.54, respectively). Fold recognition that uses data fusion to combine ranks
      calculated for both wild-type and synthetic template libraries systematically
      improves the detection of structural analogs. Depending on the threading
      algorithm used, it yields on average 4-16% higher recognition rates than using
      the wild-type template library alone. Synthetic sequences artificially evolved
      for the template structures provide an orthogonal source of signal that could be
      exploited to detect these templates unrecognized by standard modeling techniques.
      It opens up new directions in the development of more sensitive threading methods
      with the enhanced capabilities of targeting difficult, midnight zone templates.

PMID- 23542051
TI  - Computational modeling of tuberculous meningitis reveals an important role for
      tumor necrosis factor-alpha.
AB  - Tuberculosis is a global health issue with annually about 1.5 million deaths and
      2 billion infected people worldwide. Extra-pulmonary tuberculosis comprises 13%
      of all cases of which tuberculous meningitis is the most severe. It has a high
      mortality and is often diagnosed once irreversible neurological damage has
      already occurred. Development of diagnostic and treatment strategies requires a
      thorough understanding of the pathogenesis of tuberculous meningitis. This
      disease is characterized by the formation of a cerebral granuloma, which is a
      collection of immune cells that attempt to immunologically restrain, and
      physically contain bacteria. The cytokine tumor necrosis factor-alpha is known
      for its important role in granuloma formation. Because traditional experimental
      animal studies exploring tuberculous meningitis are difficult and expensive,
      another approach is needed to begin to address this important and significant
      disease outcome. Here, we present an in silico model capturing the unique
      immunological environment of the brain that allows us to study the key mechanisms
      driving granuloma formation in time. Uncertainty and sensitivity analysis reveals
      a dose-dependent effect of tumor necrosis factor-alpha on bacterial load and
      immune cell numbers thereby influencing the onset of tuberculous meningitis.
      Insufficient levels result in bacterial overgrowth, whereas high levels lead to
      uncontrolled inflammation being detrimental to the host. These findings have
      important implications for the development of immuno-modulating treatment
      strategies for tuberculous meningitis.

PMID- 23542052
TI  - In vitro biocompatiblity of modified polycarbonate as a biomaterial.
AB  - Nitrated and aminated polycarbonates were prepared chemically, characterized and
      tested in vitro as a possible biomaterial. Adhesion of Staphylococcus aureus NCIM
      5021, Escherichia coli NCIM 2931 and Proteus vulgaris NCIM 2813 and the presence
      of carbohydrate, protein, CFU and ATP on these surfaces were examined.
      Cytotoxicity of these surfaces was investigated by growing L929 mouse fibroblast
      cells. NO2-PC was more hydrophilic than un-PC and reduced adhesion of bacterial
      protein and carbohydrate. NH2-PC was the most hydrophilic surface biofilm
      prevention and increased proliferation of the fibroblast cells. The motility of
      all the three organisms decreased on aminated surface when compared to that on
      the other two. This study indicated that reducing the surface hydrophobicity
      alone was not sufficient to develop a biocompatible material, but providing
      favorable surface functional groups was also a necessary criterion. A strong
      correlation was observed between the hydrophobicity of the polymer surface and
      the zeta potential of the organism with bacterial attachment (CFU/ml). A multi
      linear regression model with these two parameters was able to fit the observed
      bacterial attachment data well.

PMID- 23542053
TI  - Effects of a computer-based cognitive exercise program on age-related cognitive
      decline.
AB  - We developed a 'senior friendly' suite of online 'games for learning' with
      interactive calibration for increasing difficulty, and evaluated the feasibility
      of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can
      improve key aspects of cognitive ability with the aid of such games. Sixty
      community-dwelling senior volunteers were randomized to either an online game
      suite designed to train multiple cognitive abilities, or to a control arm with
      online activities that simulated the look and feel of the games but with low
      level interactivity and no calibration of difficulty. Study assessment included
      measures of recruitment, retention and play-time. Cognitive change was measured
      with a computerized assessment battery administered just before and within two
      weeks after completion of the six-week intervention. Impediments to feasibility
      included: limited access to in-home high-speed internet, large variations in the
      amount of time devoted to game play, and a reluctance to pursue more challenging
      levels. Overall analysis was negative for assessed performance (transference
      effects) even though subjects improved on the games themselves. Post hoc analyses
      suggest that some types of games may have more value than others, but these
      effects would need to be replicated in a study designed for that purpose. We
      conclude that a six-week, moderate-intensity computer game-based cognitive
      intervention can be implemented with high-functioning seniors, but the effect
      size is relatively small. Our findings are consistent with Owen et al. (2010),
      but there are open questions about whether more structured, longer duration or
      more intensive 'games for learning' interventions might yield more substantial
      cognitive improvement in seniors.

PMID- 23542054
TI  - Study of TATP: method for determination of residual acids in TATP.
AB  - Triacetone triperoxide (3,3,6,6,9,9-hexamethyl-1,2,4,5,7,8-hexoxonane, TATP) is
      nowadays one of the most commonly used improvised explosives. It is prepared by
      the action of hydrogen peroxide on acetone in an acidic environment. Easily
      available mineral acids - hydrochloric, sulfuric, nitric and perchloric - are the
      most often recommended on the extremist web pages dealing with improvised
      production of explosives. The various TATP producers' choice of acid mainly
      depends on the author's experiences and the local availability of the acid. A
      knowledge of the kind of acid used for TATP production can help in detecting the
      person who has made the TATP, or who has committed a criminal act using TATP.
      Therefore, a capillary isotachophoretic method was developed for determination of
      residual anions (originating from the acid used during TATP synthesis) in the
      resulting TATP crystals. This analytical method has proved to be reliable; the
      acid used for TATP synthesis was correctly identified in all samples analyzed.

PMID- 23542055
TI  - Potential contribution of SOCC to cerebral vasospasm after experimental
      subarachnoid hemorrhage in rats.
AB  - Cerebral vasospasm (CVS) is the most treatable component of subarachnoid
      hemorrhage (SAH), which can be reduced by endothelin receptor antagonists.
      Endothelin-evoked vasospasm is considered to be mediated by Ca(2+) influx in the
      smooth muscle through voltage-dependent Ca(2+) channel (VDCC) and nonselective
      cation channels (NSCC). Because VDCC antagonists such as nimodipine have been
      shown to be relatively less effective than the endothelin receptor antagonists,
      it is assumed that NSCC maybe a more important component in mediating Ca(2+)
      influx during CVS. In this study, we used the basilar arteries from a "two
      hemorrhage" rat model of SAH to investigate expressions of transient receptor
      potential channel 1 (TRPC1), transient receptor potential channel 3 (TRPC3) and
      stromal interaction molecule 1 (STIM1), which are considered as the promising
      candidates constituting NSCC. To investigate the possible role of NSCC in
      phenotypic switching, we performed immunohistochemical staining to examine
      expressions of SMalpha-actin and PCNA, markers of smooth muscle phenotypic
      switching. We found that the basilar arteries exhibited vasospasm after SAH and
      that vasospasm became more severe on days 5 and 7 after SAH. Elevated mRNA and
      protein expressions of TRPC1 and STIM1 were detected after SAH and peaked on days
      5 and 7, which was in a parallel time course to the development of cerebral
      vasospasm. The mRNA and protein expressions of TRPC3 were not changed in the SAH
      group when compared with those in the control. Results of immunohistochemical
      staining with anti-PCNA and anti-SMalpha-actin antibodies also showed enhanced
      expression of PCNA and disappearance of SMalpha-actin from day 1 to day 7. Taken
      together, the above results supported a novel mechanism that the components of
      store-operated calcium channels, TRPC1 and STIM1 mediated the Ca(2+) influx and
      phenotypic switching in smooth muscle cells, which promoted the development of
      vasospasm after SAH. TRPC3, which is a component of receptor-operated calcium
      channels, was not involved in the above-mentioned mechanism.

PMID- 23542056
TI  - Structure of the O-specific polysaccharide from a marine bacterium Cellulophaga
      pacifica containing rarely occurred sugars, Fuc4NAc and ManNAcA.
AB  - The O-polysaccharide was isolated from the lipopolysaccharide of Cellulophaga
      pacifica and studied by chemical methods including Smith degradation as well as
      (1)H and (13)C NMR spectroscopy. The following structure of the O-polysaccharide
      of Cellulophaga pacifica containing N-acetyl-d-glucosamine (GlcNAc), 4-acetamido
      4,6-dideoxy-d-galactose (Fuc4NAc) and two residues of 2-acetamido-2-deoxy-d
      mannuronic acid (ManNAcA) was established. (Formula see text).

PMID- 23542057
TI  - Lesion HLA-F expression is irrelevant to prognosis for patients with gastric
      cancer.
AB  - Alteration of human leukocyte antigen (HLA) antigen expression has been supposed
      to play critical roles in progression of malignancies. However, clinical
      significance of the non-classical HLA class I antigen HLA-F remains largely
      unknown. In this study, HLA-F expression in 277 primary gastric cancer (GC)
      lesions was analyzed by immunohistochemistry. Data revealed that HLA-F expression
      was observed in 71.1% (197/277) of the GC lesions. Lesion HLA-F expression was
      unrelated to the clinicoparameters such as gender, age, depth of tumor invasion
      and disease stage. Survival analysis revealed that HLA-F expression in GC lesion
      was unrelated to patient prognosis (p=0.190). The mean overall survival time
      (MOS) for lesion HLA-F negative and positive patients was 11.3 months (95% CI:
      9.3-13.3) and 13.9 months (95% CI: 10.5-17.3), respectively. In conclusion, our
      study provided the evidence that HLA-F expression was unrelated to prognosis for
      patients with gastric cancer.

PMID- 23542058
TI  - Development and evaluation of loop-mediated isothermal amplification assay for
      detection of Crimean Congo hemorrhagic fever virus in Sudan.
AB  - Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) activity has been detected
      in Kordufan region of the Sudan in 2008 with high case-fatality rates in villages
      and rural hospitals in the region. Therefore, in the present study, a reverse
      transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay was
      developed and compared to nested RT-PCR for rapid detection of CCHFV targeting
      the small (S) RNA segment. A set of RT-LAMP primers, designed from a highly
      conserved region of the S segment of the viral genome, was employed to identify
      all the Sudanese CCHFV strains. The sensitivity studies indicated that the RT
      LAMP detected 10fg of CCHFV RNA as determined by naked eye turbidity read out,
      which is more likely the way it would be read in a resource-poor setting. This
      level of sensitivity is good enough to detect most acute cases. Using agarose gel
      electrophoresis, the RT-LAMP assay detected as little as 0.1fg of viral RNA
      (equivalent to 50 viral particle). There was 100% agreement between results of
      the RT-LAMP and the nested PCR when testing 10-fold serial dilution of CCHFV RNA.
      The specificity studies indicated that there was no cross-reactivity with other
      related hemorrhagic fever viruses circulating in Sudan including, Rift Valley
      fever virus (RVFV), Dengue fever virus, and yellow fever virus. The RT-LAMP was
      performed under isothermal conditions at 63 degrees C and no special apparatus
      was needed, which rendered the assay more economical and practical than real-time
      PCR in such developing countries, like Sudan. In addition, the RT-LAMP provides a
      valuable tool for rapid detection and differentiation of CCHFV during an outbreak
      of the disease in remote areas and in rural hospitals with resource-poor
      settings.

PMID- 23542059
TI  - An evaluation of the non-invasive faecal pellet assessment method as an early
      drug discovery screen for gastrointestinal liability.
AB  - INTRODUCTION: Gastrointestinal adverse effects contribute significantly to drug
      attrition as well as reduced patient compliance. Determination of
      gastrointestinal liability early in a compound's preclinical development would be
      a valuable tool. We evaluated the non-invasive faecal pellet method in the rat,
      assessed the feasibility of adding the endpoint to other study types and
      investigated correlation with the charcoal meal method. METHODS: Han Wistar rats,
      pair housed in metabolism cages, received a single dose of vehicle, atropine,
      bethanechol, loperamide or metoclopramide. The number, weight and appearance of
      pellets produced were assessed over 10 h and at 24 h post-dose. The endpoint was
      also added to a modified Irwin screen (testing atropine, theophylline, clonidine,
      amphetamine, baclofen or quinine) and a whole body plethysmography study (testing
      theophylline or bethanechol). Pellets were collected from home cages out to 4 h
      post-dose (Irwin) or following a 45 minutes plethysmography session. To assess
      correlation with stomach emptying and intestinal transit charcoal meal data was
      generated where published data was not available. RESULTS: Atropine decreased,
      while bethanechol and metoclopramide increased the number and weight of faecal
      pellets produced. Atropine produced darker, harder pellets and bethanechol
      lighter, softer pellets. Loperamide reduced pellet production at later time
      points only. Theophylline increased (Irwin and plethysmography) and atropine
      (Irwin) decreased pellet number and weight. Effects were maximal at the T(max)
      and detected in all study environments. Primary data generation was not affected
      by pellet collection. Pellet findings were generally comparable to charcoal meal
      transit data, with compounds showing an inhibition (atropine, loperamide,
      amphetamine, baclofen, clonidine, quinine) or stimulation (bethanechol) in both
      models. DISCUSSION: We have demonstrated that the faecal pellet method can detect
      expected reference compound induced changes in pellet transit. The technique is a
      useful non-invasive 'add-on' to other study types allowing gastrointestinal
      effects to be flagged earlier in preclinical development.

PMID- 23542060
TI  - Health consequences of easier access to alcohol: New Zealand evidence.
AB  - We evaluate the health effects of a reduction in New Zealand's minimum legal
      purchase age for alcohol. Difference-in-differences (DD) estimates show a
      substantial increase in alcohol-related hospitalizations among those newly
      eligible to purchase liquor, around 24.6% (s.e.=5.5%) for males and 22%
      (s.e.=8.1%) for females. There is less evidence of an effect among ineligible
      younger cohorts. There is little evidence of alcohol either complementing or
      substituting for drugs. We do not find evidence that earlier access to alcohol is
      associated with learning from experience. We also present regression
      discontinuity estimates, but emphasize DD estimates since in a simulation of a
      rational addiction model DD estimates are closer than regression discontinuity
      estimates to the policy's true effect.

PMID- 23542061
TI  - An ethanolamine-phosphate modified glycolipid in Clostridium acetobutylicum that
      responds to membrane stress.
AB  - Two phosphorus-containing glycolipids have previously been observed in
      Clostridium acetobutylicum. We had shown that the concentration of one of them
      increases in response to increased unsaturation of the membrane lipid hydrocarbon
      chains, suggesting a potential role in the regulation of lipid polymorphism in
      this organism. Mass spectrometry shows that these glycolipids are ethanolamine
      phosphate (Etn-P)-containing derivatives of a mono- and di
      glycosyldiradylglycerol. The content of both diglycosyldiradylglycerol and the
      Etn-P-monoglycosyldiradylglycerol, which increases upon increased unsaturation of
      the membrane, also increases upon addition of octanol to the medium. Thus, it
      appears that the Etn-P-monoglycosyldiradylglycerol along with the
      diglycosyldiradylglycerol may serve to stabilize the membrane bilayer during
      membrane stress caused by the presence of the solvents produced during
      fermentation.

PMID- 23542062
TI  - Characterisation of the prostaglandin E2-ethanolamide suppression of tumour
      necrosis factor-alpha production in human monocytic cells.
AB  - BACKGROUND AND PURPOSE: Prostaglandin ethanolamides or prostamides are naturally
      occurring neutral lipid derivatives of prostaglandins that have been shown to be
      synthesised in vivo following COX-facilitated oxygenation of arachidonoyl
      ethanolamine (anandamide). Although the actions of prostaglandins have been
      extensively studied, little is known about the physiological or
      pathophysiological effects of prostamides. Since prostaglandin E2 has potent
      immunosuppressive/immunomodulating actions, the aim of the present study was to
      determine whether the derivative, prostaglandin E2 ethanolamide (PGE2-EA), could
      modulate the production of the pro-inflammatory cytokine tumour necrosis factor
      alpha in human blood and human monocytic cells and indicate whether this action
      involved the same receptor systems/signals as PGE2. EXPERIMENTAL APPROACH: Whole
      human blood, monocytes isolated from the blood or the human monocytic cell line
      THP-1 was incubated with LPS and the level of TNF-alpha produced was measured by
      ELISA assay. The actions of PGE2-EA were assessed on the LPS-induced TNF-alpha
      release. In addition, in order to ascertain the receptors involved, the levels of
      cyclic AMP in cells were measured in monocytes and THP-1 cells in response to
      PGE2-EA and directly compared to those of PGE2. The effect of PGE2-EA on the
      binding of radiolabelled PGE2 to cells was also measured. Cells were incubated
      with radiolabelled arachidonic acid and ethanolamine to estimate the production
      of PGE2-EA. KEY RESULTS: PGE2-EA potently suppressed TNF-alpha production in
      blood, monocytes and the cell line THP-1 in a concentration-dependent manner.
      This occurred via cyclic AMP pathways as indicated by agents which interfere with
      these pathways and also direct ligand binding experiments. It was also shown that
      the cells were able to endogenously produce PGE2-EA. CONCLUSIONS AND
      IMPLICATIONS: This study reports that PGE2-EA can downregulate the production of
      TNF-alpha by human mononuclear cells in response to an immune stimulus, i.e. LPS
      activated TLR4, and that this appears to occur via a cAMP-dependent mechanism
      that most likely involves binding to the EP2 receptor.

PMID- 23542063
TI  - Expression pattern of vasa in gonads of sea cucumber Apostichopus japonicus
      during gametogenesis and reproductive cycle.
AB  - The vasa gene is a reliable germline marker to study the origin and development
      of germ cells and gonads, although the gene product (mRNA or protein) varies
      between different species. However, there has been little study on vasa genes in
      holothuroids to date. Here we determined the expression characteristics of the
      Apostichopus japonicus vasa gene (Aj-vasa) during gametogenesis in the ovary and
      testis using in situ hybridization and immunohistochemistry. During oogenesis,
      the expression pattern of Aj-vasa coincided at the mRNA and protein levels.
      Intensive signals in oogonia decreased gradually with the development of oocytes.
      Interestingly, the pattern was different during spermatogenesis. The Aj-vasa mRNA
      level was the highest in spermatogonia, reduced in spermatocytes, low in
      spermatids and absent in spermatozoa, but the Aj-VASA protein was restricted to
      spermatogonia and early spermatocytes. These expression characteristics of Aj
      vasa persisted in both male and female gonads throughout the reproductive cycle.
      Our findings show that Aj-vasa mRNA is a good marker for studying the origin and
      migration of germline cells; moreover, Aj-VASA is a useful tool to identify
      spermatogonia in A. japonicus. Our findings indicate that Aj-vasa is vital in the
      development and differentiation of germ cells.

PMID- 23542064
TI  - Development of electrochemical immunosensors towards point of care diagnostics.
AB  - Electrochemical immunosensors (EI) has attracted numerous interests due to its
      inherent benefits over the other transduction schemes, such as a high
      sensitivity, ease of use, a possible automation and integration in compact
      analytical devices, mostly cheap and relatively simple technology of its
      production. Thus, EIs have great potential in point of care (POC) diagnostics for
      early detection of diseases. During last decades, numerous efforts have been put
      into EIs development. Firstly, different fabrication methods and amplification
      strategies have been employed to achieve high sensitivity. To be pointed,
      nanotechnology has been involved in the fabrication and signal amplification of
      EIs, which present great superiority. Secondly, EI arrays have been used for
      multiparametric analysis. Thirdly, several attempts have been made to construct
      integrated systems, which showed promising applications for POC test. Several of
      them are commercially available for POC use. Herein, we will review briefly the
      recent achievements and progress in developing EIs towards POC diagnostics.

PMID- 23542065
TI  - Nanotechnology in glucose monitoring: advances and challenges in the last 10
      years.
AB  - In the last decades, a wide multitude of research activity has been focused on
      the development of biosensors for glucose monitoring, devoted to overcome the
      challenges associated with smart analytical performances with commercial
      implications. Crucial issues still nowadays elude biosensors to enter the market,
      such as sensitivity, stability, miniaturisation, continuous and in situ
      monitoring in a complex matrix. A noteworthy tendency of biosensor technology is
      likely to push towards nanotechnology, which allows to reduce dimensions at the
      nanoscale, consenting the construction of arrays for high throughput analysis
      with the integration of microfluidics, and enhancing the performance of the
      biological components by using new nanomaterials. This review aims to highlight
      current trends in biosensors for glucose monitoring based on nanotechnology,
      reporting widespread representative examples of the recent approaches for
      nanobiosensors over the past 10 years. Progress in nanotechnology for the
      development of biosensing systems for blood glucose level monitoring will be
      discussed, in view of their design and construction on the bases of the new
      materials offered by nanotechnology.

PMID- 23542066
TI  - Conjugated polyelectrolytes-initiated chemiluminescence: a biosensing platform
      for label-free and homogeneous DNA detection.
AB  - In this study, it was found that conjugated polyelectrolytes (CPEs) would
      initiate the strong chemiluminescence (CL) emission of luminol-H2O2 in weak basic
      media. Using CL spectra, ultraviolet visible light spectra, fluorescence spectra
      and electron spin resonance (ESR) spectra, the catalytic mechanism of CPEs on
      luminol-H2O2 CL was discussed in detail. Furthermore, it was found that the
      catalytic activity of poly [3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5
      thiophene hydro chloride] (PMNT) (a kind of cationic CPEs) on the luminol-H2O2 CL
      system was closely relevant to the conformation of PMNT. The CL intensity of
      luminol-H2O2-PMNT system in the presence of single-stranded DNA was much larger
      than that in the presence of double-stranded DNA. By taking advantage of this
      phenomenon, a label-free and homogeneous CL detection of DNA hybridization is
      proposed. The detection limit of target DNA (3sigma) was estimated to be as low
      as 3.7*10(-13)M. The present CL method for DNA hybridization detection offers the
      advantages of being simple, cheap, rapid and sensitive.

PMID- 23542067
TI  - Combination of cascade chemical reactions with graphene-DNA interaction to
      develop new strategy for biosensor fabrication.
AB  - Graphene, a single atom thick and two dimensional carbon nano-material, has been
      proven to possess many unique properties, one of which is the recent discovery
      that it can interact with single-stranded DNA through noncovalent pi-pi stacking.
      In this work, we demonstrate that a new strategy to fabricate many kinds of
      biosensors can be developed by combining this property with cascade chemical
      reactions. Taking the fabrication of glucose sensor as an example, while the
      detection target, glucose, may regulate the graphene-DNA interaction through
      three cascade chemical reactions, electrochemical techniques are employed to
      detect the target-regulated graphene-DNA interaction. Experimental results show
      that in a range from 5MUM to 20mM, the glucose concentration is in a natural
      logarithm with the logarithm of the amperometric response, suggesting a best
      detection limit and detection range. The proposed biosensor also shows favorable
      selectivity, and it has the advantage of no need for labeling. What is more, by
      controlling the cascade chemical reactions, detection of a variety of other
      targets may be achieved, thus the strategy proposed in this work may have a wide
      application potential in the future.

PMID- 23542068
TI  - Remission of Barrett's esophagus with early neoplasia 5 years after
      radiofrequency ablation with endoscopic resection: a Netherlands cohort study.
AB  - BACKGROUND & AIMS: Radiofrequency ablation (RFA), with or without endoscopic
      resection effectively eradicates Barrett's esophagus (BE) containing high-grade
      intraepithelial neoplasia and/or early-stage cancer. We followed patients who
      received RFA for BE containing high-grade intraepithelial neoplasia and/or early
      stage cancer for 5 years to determine the durability of treatment response.
      METHODS: We followed 54 patients with BE (2-12 cm), previously enrolled in 4
      consecutive cohort studies in which they underwent focal endoscopic resection in
      case of visible lesions (n = 40 [72%]), followed by serial RFA every 3 months.
      Patients underwent high-resolution endoscopy with narrow-band imaging at 6 and 12
      months after treatment and then annually for 5 years (median, 61 months;
      interquartile range, 53-65 months); random biopsy samples were collected from
      neosquamous epithelium and gastric cardia. After 5 years, endoscopic ultrasound
      and endoscopic resection of neosquamous epithelium were performed. Outcomes
      included sustained complete remission of neoplasia or intestinal metaplasia (IM),
      IM in gastric cardia, or buried glands in neosquamous epithelium. RESULTS: After
      5 years, Kaplan-Meier analysis showed sustained complete remission of neoplasia
      and intestinal metaplasia in 90% of patients; neoplasia recurred in 3 patients
      and was managed endoscopically. Focal IM in the cardia was found in 19 of 54
      patients (35%), in 53 of 1143 gastric cardia biopsies (4.6%). The incidence of IM
      of the cardia did not increase over time; and IM was diagnosed based on only a
      single biopsy in 89% of patients. Buried glands were detected in 3 of 3543
      neosquamous epithelium biopsies (0.08%, from 3 patients). No endoscopic resection
      samples had buried glands. CONCLUSIONS: Among patients who have undergone RFA
      with or without endoscopic resection for neoplastic BE, 90% remain in remission
      at 5-year follow-up, with all recurrences managed endoscopically. This treatment
      approach is therefore an effective and durable alternative to esophagectomy;
      www.trialregister.nl number, NTR2938.

PMID- 23542069
TI  - Radiofrequency ablation and endoscopic mucosal resection for dysplastic barrett's
      esophagus and early esophageal adenocarcinoma: outcomes of the UK National Halo
      RFA Registry.
AB  - BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) and high-grade
      dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal
      resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK
      registry that follows the outcomes of patients with BE who have undergone RFA for
      neoplasia. METHODS: We collected data on 335 patients with BE and neoplasia (72%
      with HGD, 24% with intramucosal cancer, 4% with low-grade dysplasia [mean age, 69
      years; 81% male]), treated at 19 centers in the United Kingdom from July 2008
      through August 2012. Mean length of BE segments was 5.8 cm (range, 1-20 cm).
      Patients' nodules were removed by endoscopic mucosal resection, and the patients
      then underwent RFA every 3 months until all areas of BE were ablated or cancer
      developed. Biopsies were collected 12 months after the first RFA; clearance of
      HGD, dysplasia, and BE were assessed. RESULTS: HGD was cleared from 86% of
      patients, all dysplasia from 81%, and BE from 62% at the 12-month time point,
      after a mean of 2.5 (range, 2-6) RFA procedures. Complete reversal dysplasia was
      15% less likely for every 1-cm increment in BE length (odds ratio = 1.156; SE =
      0.048; 95% confidence interval: 1.07-1.26; P < .001). Endoscopic mucosal
      resection before RFA did not provide any benefit. Invasive cancer developed in 10
      patients (3%) by the 12-month time point and disease had progressed in 17
      patients (5.1%) after a median follow-up time of 19 months. Symptomatic
      strictures developed in 9% of patients and were treated by endoscopic dilatation.
      Nineteen months after therapy began, 94% of patients remained clear of dysplasia.
      CONCLUSIONS: We analyzed data from a large series of patients in the United
      Kingdom who underwent RFA for BE-related neoplasia and found that by 12 months
      after treatment, dysplasia was cleared from 81%. Shorter segments of BE respond
      better to RFA; http://www.controlled-trials.com, number ISRCTN93069556.

PMID- 23542071
TI  - The effect of electroacupuncture on osteotomy gap healing in a rat fibula model.
AB  - OBJECTIVE: To examine the effect of electroacupuncture (EA) on osteotomy gap
      healing in a rat fibula model. METHODS: A total of 40 12-week-old male Wistar
      rats underwent unilateral open osteotomy of the fibula to create a 2 mm gap. The
      rats were randomly assigned to an EA group (n=20) and a control group (n=20). In
      the EA group, a cathodal electrode was connected to an acupuncture needle
      percutaneously at the surgery site, while another acupuncture needle inserted 15
      mm proximal to the surgery site was used as an anodal electrode. EA was performed
      5 days a week for 6 weeks. The control group received no treatment. Some rats
      were killed at 3 days and 1 week after surgery and the cut end of the distal part
      of the fibula was surgically removed and histologically assessed. Haematoxylin
      and eosin (H&E) staining was used to measure total cell count and
      immunohistochemical staining to assess the increase in the bone morphogenetic
      protein 2 (BMP-2)-positive cells. The healing process was also assessed weekly
      after surgery via x-ray examinations. RESULTS: At each time point, total cell
      count showed a marked increase in the EA group (p<0.05), while BMP-2 expression
      showed a tendency to increase in the EA group. Radiological examination showed a
      marked reduction in the distance between the cut ends of the fibula in the EA
      group. CONCLUSIONS: There was a marked increase in cell count and expression of
      growth factor in the EA group. These results indicate direct current EA could be
      useful for promoting bone healing.

PMID- 23542070
TI  - Irbit mediates synergy between ca(2+) and cAMP signaling pathways during
      epithelial transport in mice.
AB  - BACKGROUND & AIMS: The cyclic adenosine monophosphate (cAMP) and Ca(2+) signaling
      pathways synergize to regulate many physiological functions. However, little is
      known about the mechanisms by which these pathways interact. We investigated the
      synergy between these signaling pathways in mouse pancreatic and salivary gland
      ducts. METHODS: We created mice with disruptions in genes encoding the solute
      carrier family 26, member 6 (Slc26a6(-/-) mice) and inositol 1,4,5-triphosphate
      (InsP3) receptor-binding protein released with InsP3 (Irbit(-/-)) mice. We
      investigated fluid secretion by sealed pancreatic ducts and the function of
      Slc26a6 and the cystic fibrosis transmembrane conductance regulator (CFTR) in
      HeLa cells and in ducts isolated from mouse pancreatic and salivary glands.
      Slc26a6 activity was assayed by measuring intracellular pH, and CFTR activity was
      assayed by measuring Cl(-) current. Protein interactions were determined by
      immunoprecipitation analyses. RESULTS: Irbit mediated the synergistic activation
      of CFTR and Slc26a6 by Ca(2+) and cAMP. In resting cells, Irbit was sequestered
      by InsP3 receptors (IP3Rs) in the endoplasmic reticulum. Stimulation of Gs
      coupled receptors led to phosphorylation of IP3Rs, which increased their affinity
      for InsP3 and reduced their affinity for Irbit. Subsequent weak stimulation of Gq
      coupled receptors, which led to production of low levels of IP3, caused
      dissociation of Irbit from IP3Rs and allowed translocation of Irbit to CFTR and
      Slc26a6 in the plasma membrane. These processes stimulated epithelial secretion
      of electrolytes and fluid. These pathways were not observed in pancreatic and
      salivary glands from Irbit(-/-) or Slc26a6(-/-) mice, or in salivary gland ducts
      expressing mutant forms of IP3Rs that could not undergo protein kinase A-mediated
      phosphorylation. CONCLUSIONS: Irbit promotes synergy between the Ca(2+) and cAMP
      signaling pathways in cultured cells and in pancreatic and salivary ducts from
      mice. Defects in this pathway could be involved in cystic fibrosis, pancreatitis,
      or Sjogren syndrome.

PMID- 23542072
TI  - The lifespan-reproduction trade-off under dietary restriction is sex-specific and
      context-dependent.
AB  - Adult dietary restriction (DR) extends lifespan, but the mechanisms that underlie
      this effect are not well understood. Many DR studies have demonstrated that
      lifespan extension tends to be accompanied by a reduction in female fecundity - a
      correlation widely interpreted as evidence that DR triggers an adaptive re -
      allocation of resources from reproduction to somatic maintenance. Yet, recent
      evidence suggests that survival and fecundity need not always trade off under DR,
      calling the re-allocation hypothesis into question. Because the effects of DR on
      both survival and reproduction have rarely been tested in both sexes, or under a
      range of ecologically-relevant environments, the generality of this trade-off
      remains unclear. We examined the effects of DR on survival and reproduction in
      both sexes and across a range of environments (larval diet quality and adult sex
      ratio) in the neriid fly Telostylinus angusticollis. We found that the lifespan
      reproduction trade-off is both context- and sex-dependent. Although DR extended
      lifespan in both sexes by 65% and rendered females completely infertile, costs of
      DR on male fecundity were subtle and evident only in particular environmental
      combinations. Our findings suggest that a re-allocation of resources may not
      underlie the lifespan extension response to DR. Instead, full feeding may be
      associated with increased costs in comparison to DR, such that lifespan extension
      may be achieved without an increased resource investment to the soma.

PMID- 23542073
TI  - Trojan horse at cellular level for tumor gene therapies.
AB  - Among innovative strategies developed for cancer treatments, gene therapies stand
      of great interest despite their well-known limitations in targeting, delivery,
      toxicity or stability. The success of any given gene-therapy is highly dependent
      on the carrier efficiency. New approaches are often revisiting the mythic trojan
      horse concept to carry therapeutic nucleic acid, i.e. DNAs, RNAs or small
      interfering RNAs, to pathologic tumor site. Recent investigations are focusing on
      engineering carrying modalities to overtake the above limitations bringing new
      promise to cancer patients. This review describes recent advances and
      perspectives for gene therapies devoted to tumor treatment, taking advantage of
      available knowledge in biotechnology and medicine. 

PMID- 23542074
TI  - Deferiprone and idebenone rescue frataxin depletion phenotypes in a Drosophila
      model of Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA), the most common inherited ataxia, is a
      neurodegenerative disease caused by a reduction in the levels of the
      mitochondrial protein frataxin, the function of which remains a controversial
      matter. Several therapeutic approaches are being developed to increase frataxin
      expression and reduce the intramitochondrial iron aggregates and oxidative damage
      found in this disease. In this study, we tested separately the response of a
      Drosophila RNAi model of FRDA (Llorens et al., 2007) to treatment with the iron
      chelator deferiprone (DFP) and the antioxidant idebenone (IDE), which are both in
      clinical trials. The FRDA flies have a shortened life span and impaired motor
      coordination, and these phenotypes are more pronounced in oxidative stress
      conditions. In addition, under hyperoxia, the activity of the mitochondrial
      enzyme aconitase is strongly reduced in the FRDA flies. This study reports that
      DFP and IDE improve the life span and motor ability of frataxin-depleted flies.
      We show that DFP eliminates the excess of labile iron in the mitochondria and
      thus prevents the toxicity induced by iron accumulation. IDE treatment rescues
      aconitase activity in hyperoxic conditions. These results validate the use of our
      Drosophila model of FRDA to screen for therapeutic molecules to treat this
      disease.

PMID- 23542075
TI  - The complete mitochondrial genome sequence analysis of Tibetan argali (Ovis ammon
      hodgsoni): implications of Tibetan argali and Gansu argali as the same
      subspecies.
AB  - The genus Ovis (Bovidae, Artiodactyla) includes six species, i.e. Ovis ammon,
      Ovis aries, Ovis canadensis, Ovis dalli, Ovis nivicola and Ovis vignei. Based on
      morphology, geographical location, habitat, etc., the species O. ammon is divided
      into nine subspecies. The near threatened Tibetan argali is distributed across
      the Tibetan Plateau and its peripheral mountains, and believed to be one of the
      O. ammon subspecies (O. a. hodgsoni). However, considering its morphological
      features and distributions, a question has been proposed by some researchers
      about the subspecies status of Tibetan argali. In this study, we employed
      complete mitochondrial DNA (mtDNA) to explore the phylogenetic relationship and
      population genetic structure of Tibetan argali. The results revealed that the
      nucleotide composition, gene arrangement and codon usage pattern of the
      mitochondrial genome of Tibetan argali are similar to those of other caprines.
      Phylogenetic analyses showed that Tibetan argali was clustered with O. ammon.
      Interestingly, five Tibetan argali individuals and one of the three Gansu argali
      (O. a. dalailamae) individuals were clustered in the same branch, which is a
      sister group to other two Gansu argali individuals. Together with morphological
      characteristics, our results suggested that Tibetan argali and Gansu argali may
      belong to the same subspecies (O. a. hodgsoni) of O. ammon, rather than two
      different subspecies.

PMID- 23542076
TI  - Molecular and clinical evaluation of Turkish patients with lysinuric protein
      intolerance.
AB  - Lysinuric protein intolerance is an autosomal recessive metabolic disorder caused
      by defective transport of the cationic amino acids lysine, arginine and ornithine
      in the epithelial cells of the basolateral membrane in the small intestine and
      renal tubules. Mutations in the solute carrier family 7, member 7, SLC7A7, gene
      cause this multisystemic disease with a variety of clinical symptoms such as
      hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary
      insufficiency or end-stage renal disease. In the present study, genomic structure
      of SLC7A7 in six Turkish patients with lysinuric protein intolerance was examined
      in order to detect disease causing mutations by denaturing high pressure liquid
      chromatography and direct sequencing. Four novel mutations were identified in
      SLC7A7: c.223insGTC, p.Val74_Ile75insVal; c.283insTGG, p.Glu94_Thr95insTrp;
      c.344_347delTTGC, p.Leu115LeufsX53; and c.1099insT, p.Ile367TyrfsX16. Clinical
      and biochemical findings were evaluated together with these molecular analyses.

PMID- 23542077
TI  - Methylenetetrahydrofolate reductase C677T variant in Moroccan patients with
      inflammatory bowel disease.
AB  - BACKGROUND: The association of genetic polymorphisms related to metabolism of
      homocysteine and folate with inflammatory bowel disease has been evidenced.
      Several studies have identified genetic variants of MTHFR as significant
      susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The
      C677T genetic polymorphism in the MTHFR gene is found to be associated with a
      thermolabile variant enzyme that shows a reduced activity. Therefore, we
      investigated whether the C677T variant confers genetic susceptibility to CD or UC
      and evaluated the genotype-phenotype associations in the Moroccan population.
      METHODS: The present study included 96 inflammatory bowel disease patients (68
      patients with CD and 28 with UC) and 182 healthy controls. DNA samples were
      genotyped for the MTHFR (C677T) mutation by the PCR-RFLP method. Statistical
      analyzes were performed using MedCalc software, Chi square test and Fisher test.
      RESULTS: The respective odds ratio for CD, UC and control group were, 1.55 (CI
      95%: 0.53-4.53, P=0.52); 0.50 (CI 95%: 0.06-4.15, P=0.52) and 0.50 (CI 95%: 0.06
      4.15, P=0.52). Thus, no statistically significant association with the disease
      was observed in frequency of the TT variant in comparison to healthy controls.
      Stratification of IBD patients on the basis of CD or UC showed that individuals
      carrying at least one T allele are not protected against Crohn's disease.
      Furthermore, clinical features of the disease did not show any significant
      association. CONCLUSION: In conclusion, the present study indicates that the
      genetic risk for IBD is not modulated by MTHFR C677T polymorphism in Moroccan
      population.

PMID- 23542078
TI  - Impact of anaesthetics and surgery on neurodevelopment: an update.
AB  - Accumulating preclinical and clinical evidence suggests the possibility of
      neurotoxicity from neonatal exposure to general anaesthetics. Here, we review the
      weight of the evidence from both human and animal studies and discuss the
      putative mechanisms of injury and options for protective strategies. Our review
      identified 55 rodent studies, seven primate studies, and nine clinical studies of
      interest. While the preclinical data consistently demonstrate robust apoptosis in
      the nervous system after anaesthetic exposure, only a few studies have performed
      cognitive follow-up. Nonetheless, the emerging evidence that the primate brain is
      vulnerable to anaesthetic-induced apoptosis is of concern. The impact of surgery
      on anaesthetic-induced brain injury has not been adequately addressed yet. The
      clinical data, comprising largely retrospective cohort database analyses, are
      inconclusive, in part due to confounding variables inherent in these
      observational epidemiological approaches. This places even greater emphasis on
      prospective approaches to this problem, such as the ongoing GAS trial and PANDA
      study.

PMID- 23542079
TI  - The evolution of genomic instability in the obligate endosymbionts of whiteflies.
AB  - Many insects depend on ancient associations with intracellular bacteria to
      perform essential metabolic functions. These endosymbionts exhibit striking
      examples of convergence in genome architecture, including a high degree of
      structural stability that is not typical of their free-living counterparts.
      However, the recently sequenced genome of the obligate whitefly endosymbiont
      Portiera revealed features that distinguish it from other ancient insect
      associates, such as a low gene density and the presence of perfectly duplicated
      sequences. Here, we report the comparative analysis of Portiera genome sequences
      both within and between host species. In one whitefly lineage (Bemisia tabaci),
      we identify large-scale structural polymorphisms in the Portiera genome that
      exist even within individual insects. This variation is likely mediated by
      recombination across identical repeats that are maintained by gene conversion.
      The complete Portiera genome sequence from a distantly related whitefly host
      (Trialeurodes vaporarium) confirms a history of extensive genome rearrangement in
      this ancient endosymbiont. Using gene-order-based phylogenetic analysis, we show
      that the majority of rearrangements have occurred in the B. tabaci lineage,
      coinciding with an increase in the rate of nucleotide substitutions, a
      proliferation of short tandem repeats (microsatellites) in intergenic regions,
      and the loss of many widely conserved genes involved in DNA replication,
      recombination, and repair. These results indicate that the loss of
      recombinational machinery is unlikely to be the cause of the extreme structural
      conservation that is generally observed in obligate endosymbiont genomes and that
      large, repetitive intergenic regions are an important substrate for genomic
      rearrangements.

PMID- 23542080
TI  - Antagonists reversibly reverse chemical LTD induced by group I, group II and
      group III metabotropic glutamate receptors.
AB  - Metabotropic glutamate (mGlu) receptors are implicated in many neurological and
      psychiatric diseases and are the targets of therapeutic agents currently in
      clinical development. Their activation has diverse effects in the central nervous
      system (CNS) that includes an involvement in synaptic plasticity. We previously
      reported that the brief exposure of hippocampal slices to dihydroxyphenylglycine
      (DHPG) can result in a long-term depression (LTD) of excitatory synaptic
      transmission. Surprisingly, this LTD could be fully reversed by mGlu receptor
      antagonists in a manner that was itself fully reversible upon washout of the
      antagonist. Here, 15 years after the discovery of DHPG-LTD and its reversible
      reversibility, we summarise these initial findings. We then present new data on
      DHPG-LTD, which demonstrates that evoked epileptiform activity triggered by
      activation of group I mGlu receptors can also be reversibly reversed by mGlu
      receptor antagonists. Furthermore, we show that the phenomenon of reversible
      reversibility is not specific to group I mGlu receptors. We report that
      activation of group II mGlu receptors in the temporo-ammonic pathway (TAP) and
      mossy fibre pathway within the hippocampus and in the cortical input to neurons
      of the lateral amygdala induces an LTD that is reversed by LY341495, a group II
      mGlu receptor antagonist. We also show that activation of group III mGlu8
      receptors induces an LTD at lateral perforant path inputs to the dentate gyrus
      and that this LTD is reversed by MDCPG, an mGlu8 receptor antagonist. In
      conclusion, we have shown that activation of representative members of each of
      the three groups of mGlu receptors can induce forms of LTD than can be reversed
      by antagonists, and that in each case washout of the antagonist is associated
      with the re-establishment of the LTD. This article is part of the Special Issue
      entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. 

PMID- 23542082
TI  - Preprocedural distress in children with cancer: an intervention using biofeedback
      and relaxation.
AB  - Children diagnosed with cancer experience many invasive procedures throughout
      diagnosis and treatment of their disease. These procedures, oftentimes a source
      of distress in children, can elicit a variety of anticipatory symptoms prior to
      the actual procedure. Although there have been efforts to develop approaches to
      alleviate this distress through use of distraction, relaxation, sedation, guided
      imagery, and hypnosis, there has not been a combination treatment that merged
      relaxation techniques and biofeedback within a pediatric framework. A group of 12
      children diagnosed with cancer participated in a 4-session intervention combining
      relaxation and biofeedback. This feasibility study suggests that the combination
      intervention offered in a clinical setting may be beneficial to children
      experiencing procedural distress as a novel coping strategy.

PMID- 23542081
TI  - Adipose-specific lipoprotein lipase deficiency more profoundly affects brown than
      white fat biology.
AB  - Adipose fat storage is thought to require uptake of circulating triglyceride (TG)
      derived fatty acids via lipoprotein lipase (LpL). To determine how LpL affects
      the biology of adipose tissue, we created adipose-specific LpL knock-out (ATLO)
      mice, and we compared them with whole body LpL knock-out mice rescued with muscle
      LpL expression (MCK/L0) and wild type (WT) mice. ATLO LpL mRNA and activity were
      reduced, respectively, 75 and 70% in gonadal adipose tissue (GAT), 90 and 80% in
      subcutaneous tissue, and 84 and 85% in brown adipose tissue (BAT). ATLO mice had
      increased plasma TG levels associated with reduced chylomicron TG uptake into BAT
      and lung. ATLO BAT, but not GAT, had altered TG composition. GAT from MCK/L0 was
      smaller and contained less polyunsaturated fatty acids in TG, although GAT from
      ATLO was normal unless LpL was overexpressed in muscle. High fat diet feeding led
      to less adipose in MCK/L0 mice but TG acyl composition in subcutaneous tissue and
      BAT reverted to that of WT. Therefore, adipocyte LpL in BAT modulates plasma
      lipoprotein clearance, and the greater metabolic activity of this depot makes its
      lipid composition more dependent on LpL-mediated uptake. Loss of adipose LpL
      reduces fat accumulation only if accompanied by greater LpL activity in muscle.
      These data support the role of LpL as the "gatekeeper" for tissue lipid
      distribution.

PMID- 23542083
TI  - Disclosure of confidential patient information and the duty to consult: the role
      of the health and social care information centre.
AB  - Before disclosing confidential patient information for purposes not directly
      related to his or her care and treatment, there is currently a responsibility
      upon health professionals to consult with a patient wherever practicable. The
      Health and Social Care Act 2012 has diluted that responsibility to consult, at
      least in relation to any information that the Health and Social Care Information
      Centre requires health professionals to disclose. This is at odds with other
      moves to support an individual's involvement in decisions that affect them.
      Moreover, a responsibility to consult can be shown to be a procedural aspect of
      the fundamental right to respect for private and family life as guaranteed by
      Article 8 of the European Convention on Human Rights (ECHR). The scope and nature
      of a procedural requirement for consultation can be revealed, at least in part,
      by considering the case law concerning disclosure in the field of criminality
      information sharing. If the Health and Social Care Act 2012 is to be adequately
      protected from a challenge for incompatibility with the ECHR, then practicable
      opportunities to provide information about the intended purposes of processing,
      and respect for any reasonable objection to disclosure, must be recognised beyond
      those explicitly provided for by the 2012 Act. The Code of Practice that the
      Information Centre is responsible for producing represents an opportunity to
      guarantee adequate levels of consultation will be preserved, consistent with
      proposed changes to the NHS Constitution. 

PMID- 23542084
TI  - A highly sensitive differential pulse anodic stripping voltammetry for
      determination of 17beta-estradiol (E2) using CdSe quantum dots based on indirect
      competitive immunoassay.
AB  - In this study a new and fast procedure was developed to determine trace 17beta
      estradiol (E2) concentrations using CdSe quantum dots (QDs) conjugation with
      bovine serum albumin (BSA)-E2. To increase the high efficiency of the method, the
      immunoassay design was restricted to an indirect competitive format. The E2
      antigen and bioconjugate were incubated in a microtiter plate with an anti-E2
      antibody and competition for antibody binding sites was established. The in situ
      bismuth-coated carbon electrodes were used for detecting the cadmium ions
      (Cd(2+)) released during the acid dissolution step. After optimization, the well
      defined sharp anodic stripping voltammograms curves of the E2 concentration
      ranging from 50 to 1000 pg/mL was recorded, and the lowest detection limit was 50
      pg/mL with 6% reproducibility and 7% repeatability. Finally, the assay was
      applied to tap water and wastewater samples. The detection limits were 52.56 +/-
      0.125 pg/mL for tap water and 51.42 +/- 0.453 pg/mL for wastewater. These results
      show that the assay exhibited sensitive analytical performance in E2 detection
      with high sensitivity and accuracy with satisfactory results.

PMID- 23542085
TI  - Detection of cancer biomarkers by piezoelectric biosensor using PZT ceramic
      resonator as the transducer.
AB  - A novel piezoelectric biosensor using lead titanate zirconate (PZT) ceramic
      resonator as transducer was developed for label-free, cost-effective, and direct
      detection of cancer biomarkers. We designed a dual sensing scheme where two
      ceramic resonators were connected in parallel, in which one resonator was used as
      the sensing unit and the other as the control unit, in order to minimize
      environment influences including temperature fluctuation and to achieve the
      required frequency stability for biosensing applications. Detection of selected
      cancer biomarkers, such as prostate specific antigen (PSA) and alpha-fetoprotein
      (AFP) was carried out to evaluate the performance of the biosensor. The device
      showed high sensitivity (0.25 ng/ml) and fast detection (within 30 min) with
      small amount of sample (1 MUl), which is compatible to that required by clinical
      measurements. The results also showed that the ceramic resonator-based
      piezoelectric biosensor platform could be utilized with different chemical
      interfaces, and the miniaturized size of the ceramic resonators makes it suitable
      for fabricating sensor arrays for multiplex detection.

PMID- 23542086
TI  - NT-proANP and NT-proBNP as prognostic markers in patients with acute
      decompensated heart failure of different etiologies.
AB  - BACKGROUND AND PURPOSE: Peak NT-proANP and NT-proBNP plasma levels after hospital
      admission may be of additional prognostic value in patients with acute
      decompensation of heart failure. The time-course of natriuretic plasma levels
      after hospital admission, and a possible influence of the underlying etiology on
      the time-course have not been sufficiently investigated. METHODS AND RESULTS:
      Natriuretic peptide plasma levels of 85 patients with decompensated heart failure
      from ischemic and non-ischemic origins were measured at baseline and at 12h after
      hospital admission. NT-proBNP plasma levels on admission were lower compared to
      12-hour-plasma levels, whereas NT-proANP plasma levels on admission were higher
      compared to 12-hour-plasma levels. Twenty-six patients (31%) died within the
      first 30 days. In patients who died within the first 30 days after admission NT
      proANP and NT-proBNP plasma levels on admission and 12h later were significantly
      higher compared to survivors. Irrespective of different etiologies NT-proANP on
      admission and NT-proBNP 12h after admission were highest and demonstrated
      superior impact with respect to the prediction of 30-day-mortality. CONCLUSIONS:
      NT-proANP and NT-proBNP are powerful markers of 30-day-mortality in patients with
      acute heart failure of ischemic and non-ischemic origins. With respect to the
      prediction of 30-day-mortality, NT-proBNP plasma levels at 12h after admission
      are comparable with NT-proANP plasma levels on admission. These data underline
      the fact that with regard to etiology-dependent hemodynamic changes and plasma
      half-time, the determination of peak plasma levels is of highest importance for
      the estimation of the impact of natriuretic peptides on the prognosis of patients
      with decompensated heart failure.

PMID- 23542087
TI  - The effects of central pro-and anti-inflammatory immune challenges on depressive
      like behavior induced by chronic forced swim stress in rats.
AB  - Although increasing evidence demonstrates that both chronic stressors and
      inflammatory immune activation contribute to pathophysiology and behavioral
      alterations associated with major depression, little is known about the
      interaction effect of central inflammatory immune activation and stress on
      depressive-like behavior. Our previous work has shown that 14-day chronic forced
      swim stress induces significant depressive-like behavior. The present
      investigation assessed whether pro-inflammatory cytokine and anti-inflammatory
      cytokine challenges have differential interaction effect on depressive-like
      behavior induced by chronic forced swim stress in rats. The pro-inflammatory and
      anti-inflammatory immune challenges were achieved respectively by central
      administration of lipopolysaccharide (LPS), a pro-inflammatory cytokine inducer,
      and interleukin-10 (IL-10), an anti-inflammatory cytokine. It was found that
      either central LPS treatment alone or chronic forced swim stress alone
      significantly induced depressive-like behavior, including reduced body weight
      gain, reduced saccharin preference and reduced locomotor activity. However, there
      was no significant synergistic or additive effect of central LPS treatment and
      stress on depressive-like behavior. LPS treatment did not exacerbate the
      depressive-like behavior induced by forced swim stress. Nevertheless, IL-10
      reversed depressive-like behavior induced by forced swim stress, a finding
      indicating that IL-10 has antidepressant effect on behavioral depression induced
      by stress. The present findings provide new insight into the complexity of the
      immunity-inflammation hypothesis of depression.

PMID- 23542088
TI  - Disruption of footshock-induced theta rhythms by stimulating median raphe nucleus
      reduces anxiety in rats.
AB  - Theta rhythms generated in the hippocampus are controlled by the pacemaker in the
      medial septum-diagonal band of Broca (MS-DBB). The median raphe nucleus (MRN)
      transmits serotonergic signals to the MS-DBB, which suppresses the septo
      hippocampus-produced theta waves, whereas GABAergic interneurons in the MRN
      facilitate the generation of theta oscillations. Animal studies have indicated
      that fear increases theta oscillations. Moreover, anxiolytics reduce reticular
      formation-elicited theta rhythms and theta blockade decreases anxiety. In this
      study, we hypothesized that the MRN mediates anxiety reduction caused by the
      theta blockade. Our results demonstrated that inescapable-footshock stimulation
      significantly increased the power of low-frequency theta oscillations (4-7 Hz) in
      rats. Both the electrical stimulation of MRN and administration of bicuculline
      into the MRN successfully desynchronized footshock-induced theta oscillations.
      Compared to the naive rats, inescapable-footshock stimulation diminished the
      entry percentage and time spent in the open arms of the elevated plus maze (EPM),
      behavioral indicators of anxiety. Rats treated with either MRN stimulation or
      bicuculline administration to desynchronize theta oscillations reduced anxiety
      caused by the inescapable-footshock stimulation. Our results demonstrated that
      the electrical stimulation of MRN or blockade of the GABAergic pathways in the
      MRN interferes with theta oscillations and reduces anxiety, implicating the role
      of MRN.

PMID- 23542089
TI  - Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular
      signature and clinical management.
AB  - There is ample epidemiologic evidence for an association of chronic hepatitis C
      virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes
      most frequently associated with HCV are marginal zone lymphoma and diffuse large
      B-cell lymphoma. The most convincing evidence for a causal relationship between
      HCV infection and lymphoma development is the observation of B-NHL regression
      after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV
      associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be
      considered. Molecular mechanisms of HCV-NHL development are still poorly
      understood. Three general theories have emerged to understand the HCV-induced
      lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by
      viral antigens and consecutive proliferation; (2) HCV replication in B cells with
      oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell
      damage, e.g., mutation of tumor suppressor genes, caused by a transiently
      intracellular virus ("hit and run" theory). This review systematically summarizes
      the data on epidemiology, interventional studies, and molecular mechanisms of HCV
      associated B-NHL.

PMID- 23542090
TI  - Targeting Lyme disease.

PMID- 23542091
TI  - Physical harm due to chronic substance use.
AB  - Chronic use at high dose of illicit drugs, alcohol and tobacco is associated with
      physical disease. The relative physical harm of these substances has not been
      described before, but will benefit the guiding of policy measures about licit and
      illicit substances. The physical harm of 19 addictive substances (including
      alcohol and tobacco), consisting of toxicity and the risk and severity of somatic
      disease (not psychiatric disease) was assessed based on literature data and the
      professional opinion of experts using scores ranging from 0 (no physical harm) to
      3 (very serious physical harm). For alcohol, tobacco and some illicit drugs
      strong associations between long-term use or use in high dose versus the risk of
      somatic disease have been described, whereas for other substances such data are
      not available. Magic mushrooms, LSD and methylphenidate obtained relatively low
      scores (0.45-0.65) for physical harm, whereas relatively high scores were given
      for heroin (2.09), crack (2.32), alcohol (2.13) and tobacco (2.10). For cannabis,
      tobacco, and alcohol the estimated societal disease burden was higher than at
      individual level. The present ranking solely based on their physical harm was
      very similar to a previous ranking based on a combination of dependence
      liability, physical harm and social impairments.

PMID- 23542092
TI  - Phylogenetic relationships among Sarcocystis species in cervids, cattle and sheep
      inferred from the mitochondrial cytochrome c oxidase subunit I gene.
AB  - Coccidian parasites in the genus Sarcocystis have a two-host life cycle, and have
      traditionally been identified on the basis of morphological features of the
      sarcocyst stage in their intermediate hosts. Additional molecular species
      identification, delimitation and phylogeny of Sarcocystis spp. have been based
      mainly on the nuclear ssrRNA gene. This gene is well suited for discrimination
      between more distant species but less so for closely related species. The
      objective of this study was therefore to establish the mitochondrial cytochrome c
      oxidase subunit I gene (cox1) as a novel genetic marker for Sarcocystis spp. and
      assess its utility for species identification and delimitation. New primers were
      developed and 1,020-1,095 bp long cox1 sequences were obtained from 155 isolates
      of 22 Sarcocystis spp. from cattle, sheep, red deer, reindeer, roe deer and
      moose, and used for phylogenetic reconstructions. For 18 species, the
      intraspecific and interspecific sequence identities were 98.5-100% and 58-92%,
      respectively. The four other species had previously been regarded as two species
      (Sarcocystis rangiferi, Sarcocystis tarandi), each infecting both reindeer and
      red deer. From cox1 data, each of those appeared to be two separate species, with
      S. rangiferi and S. tarandi being restricted to reindeer. Thus, cox1 sequences
      seem to perform better than ssrRNA gene sequences for delimitation of closely
      related species. The 22 species were distributed in three major clades according
      to their definitive hosts as in phylogenetic trees obtained from the ssrRNA gene.
      There were only minor differences in the branching order of different taxa
      between the trees obtained from either gene. This study has successfully
      established cox1 as a novel genetic marker for future research on Sarcocystis
      spp. It has also provided the first published molecular identification of
      Sarcocystis gigantea and Sarcocystis tenella in Norwegian sheep, and of
      Sarcocystis hirsuta and Sarcocystis sinensis in Argentinean cattle.

PMID- 23542093
TI  - Identification of a protein interacting with the spore wall protein SWP26 of
      Nosema bombycis in a cultured BmN cell line of silkworm.
AB  - Nosema bombycis is a silkworm parasite that causes severe economic damage to
      sericulture worldwide. It is the first microsporidia to be described in the
      literature, and to date, very little molecular information is available regarding
      microsporidian physiology and their relationships with their hosts. Therefore,
      the interaction between the microsporidia N. bombycis and its host silkworm,
      Bombyx mori, was analyzed in this study. The microsporidian spore wall proteins
      (SWPs) play a specific role in spore adherence to host cells and recognition by
      the host during invasion. In this study, SWP26 fused with enhanced green
      fluorescence protein (EGFP) was expressed in BmN cells by using a Bac-to-Bac
      expression system. Subsequently, the turtle-like protein of B. mori (BmTLP) was
      determined to interact with SWP26 via the use of anti-EGFP microbeads. This
      interaction was then confirmed by yeast two-hybrid analysis. The BmTLP cDNA
      encodes a polypeptide of 447 amino acids that includes a putative signal peptide
      of 27 amino acid residues. In addition, the BmTLP protein contains 2
      immunoglobulin (IG) domains and 2 IGc2-type domains, which is the typical domain
      structure of IG proteins. The results of this study indicated that SWP26
      interacts with the IG-like protein BmTLP, which contributes to the infectivity of
      N. bombycis to its host silkworm.

PMID- 23542094
TI  - The first genetic characterization of a D4 measles virus strain derived from a
      patient with subacute sclerosing panencephalitis.
AB  - Measles virus (MV) strains derived from patients with subacute sclerosing
      panencephalitis (SSPE), SSPE strains, possess numerous mutations when compared to
      viruses belonging to the same genotype and circulating in similar time period.
      Although many SSPE strains have been extensively characterized, none of them
      belongs to D4 genotype which currently predominates in Europe where it has caused
      a number of recent outbreaks/epidemics. We sequenced an MV derived from a patient
      with long-term SSPE; the virus was named MVs/Zagreb.CRO/30.06[D4] (SSPE). Initial
      genetic analysis showed that it belongs to D4 genotype. The sequences of genes
      encoding matrix and fusion proteins indicate premature protein terminations.
      Putative hemagglutin (H) protein is lengthened for 20 amino acids, which is the
      longest H protein elongation so far found in SSPE viruses. Nucleotides 1421 A,
      1422 G, 1507 C and 1542 C in nucleoprotein gene open reading frame seem to be
      specific for this D4 strain, differentiating it from other D4 non-SSPE strains.
      Besides, a unique mutation at position 543 of H protein was found, histidine
      instead of tyrosine. As persistent MV infections are initially established by
      "normal" wild-type MV strains, the presented comparative analyses describe
      alterations that could be involved in the maintenance of persistent infection,
      disease development and progression.

PMID- 23542095
TI  - Genetic diversity of G9P[8] rotavirus strains circulating in Italy in 2007 and
      2010 as determined by whole genome sequencing.
AB  - This study reports the molecular characterization of G9P[8] rotavirus strains
      from children with acute diarrhea identified in different cities of Italy, in
      2007 and 2010. Seventeen samples exhibited a G9P[8] genotype by RT-PCR and semi
      nested PCR. Preliminary sequence analysis of the VP7 and VP8(*) encoding genes
      revealed nucleotide identities ranging between 96% and 100%. Full genome
      sequencing of four G9P[8] strains selected in different cities or years showed
      that the investigated Italian strains possessed a complete Wa-like genotype
      constellation. However, phylogenetic analyses assigned strains to different
      clusters reflecting point mutations and possibly earlier reassortment between Wa
      like RVA strains. Deduced amino acid sequence of the VP7 and VP4 genes for the
      G9P[8] strains revealed at least five substitutions in relevant antigenic sites
      of both proteins.

PMID- 23542096
TI  - Not all subintimal chronic total occlusion revascularization is alike.

PMID- 23542097
TI  - Right atrial rupture in angiosarcoma.

PMID- 23542098
TI  - Reply: To PMID 23428214.

PMID- 23542099
TI  - "Cherry-picking" patients for randomized, controlled trials--reliving the
      past....

PMID- 23542100
TI  - Reducing hospitalizations for acute decompensated heart failure: the infusion
      room approach.

PMID- 23542101
TI  - Reply: To PMID 23177300.

PMID- 23542102
TI  - Reply: To PMID 23273395.

PMID- 23542103
TI  - Reply: To PMID 23246392.

PMID- 23542104
TI  - Does the absence of comorbidities really identify low-risk syncope patients?

PMID- 23542105
TI  - Reply: To PMID 23265340.

PMID- 23542106
TI  - Issues needing clarification regarding population characteristics in the analysis
      from the National Cardiovascular Data Registry.

PMID- 23542107
TI  - Reply: To PMID 23273288.

PMID- 23542108
TI  - Reply: To PMID 23391193.

PMID- 23542109
TI  - Cardiac troponin: a villain or a decent actor in the process of ongoing
      myocardial injury?

PMID- 23542110
TI  - A heart of stone: rapid metastatic cardiac calcification in an end-stage renal
      disease patient.

PMID- 23542111
TI  - Do work accidents play any role in the increased risk of death observed in 25- to
      44-year-old patients after syncope?

PMID- 23542112
TI  - Prevalence and predictors of gaps in care among adult congenital heart disease
      patients: HEART-ACHD (The Health, Education, and Access Research Trial).
AB  - OBJECTIVES: The goal of this project was to quantify the prevalence of gaps in
      cardiology care, identify predictors of gaps, and assess barriers to care among
      adult congenital heart disease (adult CHD) patients. BACKGROUND: Adult CHD
      patients risk interruptions in care that are associated with undesired outcomes.
      METHODS: Patients (18 years of age and older) with their first presentation to an
      adult CHD clinic completed a survey regarding gaps in, and barriers to, care.
      RESULTS: Among 12 adult CHD centers, 922 subjects (54% female) were recruited. A
      >3-year gap in cardiology care was identified in 42%, with 8% having gaps longer
      than a decade. Mean age at the first gap was 19.9 years. The majority of
      respondents had more than high school education and knew their heart condition.
      The most common reasons for gaps included feeling well, being unaware that follow
      up was required, and complete absence from medical care. Disease complexity was
      predictive of a gap in care with 59% of mild, 42% of moderate, and 26% of severe
      disease subjects reporting gaps (p < 0.0001). Clinic location significantly
      predicted gaps (p < 0.0001), whereas sex, race, and education level did not.
      Common reasons for returning to care were new symptoms, referral from provider,
      and desire to prevent problems. CONCLUSIONS: Adult CHD patients have gaps in
      cardiology care; the first lapse commonly occurred at age ~19 years, a time when
      transition to adult services is contemplated. Gaps were more common among
      subjects with mild and moderate diagnoses and at particular locations. These
      results provide a framework for developing strategies to decrease gaps and
      address barriers to care in the adult CHD population.

PMID- 23542113
TI  - Clarification of the pre- and post-treatment parameter for erectile dysfunction
      treatment.

PMID- 23542114
TI  - Arsenic trioxide depletes cancer stem-like cells and inhibits repopulation of
      neurosphere derived from glioblastoma by downregulation of Notch pathway.
AB  - Notch signaling has been demonstrated to have a central role in cancer stem-like
      cells (CSLCs) in glioblastoma multiforme (GBM). We have recently demonstrated the
      inhibitory effect of arsenic trioxide (ATO) on CSLCs in glioblastoma cell lines.
      In this study we used neurosphere recovery assay that measured neurosphere
      formation at three time points to assess the capacity of the culture to
      repopulate after ATO treatment. Our results provided strong evidence that ATO
      depleted CSLCs in GBM, and inhibited neurosphere recovery and secondary
      neurosphere formation. ATO inhibited the phosphorylation and activation of AKT
      and STAT3 through Notch signaling blockade. These data show that the ATO is a
      promising new approach to decrease glioblastoma proliferation and recurrence by
      downregulation of Notch pathway.

PMID- 23542115
TI  - The effects of liquid versus spray-dried Laminaria digitata extract on selected
      bacterial groups in the piglet gastrointestinal tract (GIT) microbiota.
AB  - In this study, the effects of supplementing animal feed with a liquid and spray
      dried fucoidan and laminarin extract, derived from the seaweed Laminaria digitata
      on the porcine gastrointestinal microbiota, specifically the communities of
      Lactobacillus, Bifidobacterium and enterobacteria were evaluated. Twenty four
      piglets were fed one of three diets over a 21-day period to determine the effect
      that each had on the bacterial communities. The dietary treatments were as
      follows; (1) control diet, (2) control diet plus spray-dried formulation of
      laminarin fucoidan (L/F-SD) extract, (3) control diet plus a liquid formulation
      of (L/F-WS) extract. Control diet consisted of wheat, soya bean meal, soya oil
      and a vitamin and mineral mixture. The L/F-SD and L/F-WS supplemented diets had
      equal proportion of 500 ppm laminarin and fucoidan. At the end of the 21 day
      feeding period all animals were sacrificed and samples were collected from the
      ileum, caecum and colon. Counts were determined for Lactobacillus,
      Bifidobacterium and enterobacteria. Plate count analysis revealed that the L/F-SD
      diet caused a statistically significant 1.5 log and 2 log increases in the
      Lactobacillus and Bifidobacterium counts of ileum samples respectively. A greater
      difference was observed with the L/F-WS diet in that Lactobacillus and
      Bifidobacterium increased by 2 log and 3 log respectively. Alterations in the
      Lactobacillus species composition of the gastrointestinal tract (GIT) were
      analysed using specific PCR - denaturing gradient gel electrophoresis (PCR-DGGE).
      The DGGE profiles indicated that Lactobacillus species richness decreased along
      the gastrointestinal tract i.e. the number of dominant species detected in the
      colon was less than those detected in the ileum and caecum irrespective of the
      diet consumed. Consumption of both the L/F-SD and L/F-WS diets resulted in a
      richer Lactobacillus species composition in the ileum, with the L/F-SD diet being
      associated the emergence of Lactobacillus agilis in the colon. The study
      indicated that the L/F-WS extract was superior to the L/F-SD extract in
      increasing the titre of beneficial bacteria in the gastrointestinal tract (GIT).

PMID- 23542116
TI  - Protective effect of a mixture of kefir-isolated lactic acid bacteria and yeasts
      in a hamster model of Clostridium difficile infection.
AB  - The objective of this work was to test the protective effect of a mixture (MM)
      constituted by kefir-isolated microorganisms (Lactobacillus plantarum,
      Lactobacillus kefir, Lc. lactis, Kluyveromyces marxianus and Saccharomyces
      cerevisiae) in a hamster model of infection with Clostridium difficile, an
      anaerobic Gram-positive bacterium that causes diarrhoea. Placebo or MM was
      administered ad libitum in drinking water from day 0 to the end of treatment.
      Hamsters received orally 200 MUg of clyndamicin at day 7 and then were infected
      with 1 * 10(8) CFU of C. difficile by gavage. Development of diarrhoea and death
      was registered until the end of the protocol. Surviving animals were sacrificed
      at day 16, and a test for biological activity of clostridial toxins and
      histological stainings were performed in caecum samples. Six of seven infected
      animals developed diarrhoea and 5/7 died at the end of the experimental protocol.
      The histological sections showed oedema and inflammatory infiltrates with
      neutrophils and crypt abscesses. In the group of animals infected and treated
      with MM1/1000, only 1 of 7 hamsters showed diarrhoea and none of them died. The
      histological sections showed only a slight thickening of the mucosa with presence
      of lymphocytic infiltrate. These results demonstrate that an oral treatment with
      a mixture of kefir-isolated bacteria and yeasts was able to prevent diarrhoea and
      enterocolitis triggered by C. difficile.

PMID- 23542117
TI  - Non-specificity of primers used for PCR based serogrouping of Dichelobacter
      nodosus and identification of a novel D. nodosus strain.
AB  - The present study records the first case of non-specificity of typing primers
      developed by Dhungyel et al. A strain of Dichelobacter nodosus (JKS-20G) isolated
      from ovine footrot in Kashmir, India, showed specificity for serogroup C and G
      primers. The fimA sequence of the strain turned out to be closer to serogroup G
      than C. The nucleotide sequence showed maximum homology of 92% with that of
      serotype G1 strain 238 and 95% with partial sequence available for serotype G2
      strain VCS 1004. However, the deduced amino acid sequence of the fimbrial subunit
      gene of JKS-20G differed from strain 238 by 16 amino acids and by four amino
      acids from that of partial sequence of strain VCS 1004. This variation indicates
      towards declaring this isolate as a new serotype (G3) but just insufficient to
      classify this into a new serogroup. Some of the amino acid substitutions were
      located within three hypervariable regions a characteristic of different
      serogroups. However, to ascertain whether this isolate deserves a new serotype
      status, there is a need to go for antigenic characterisation of this isolate
      using the tube and cross tube agglutination test.

PMID- 23542118
TI  - Can scintillation detectors with low spectral resolution accurately determine
      radionuclides content of building materials?
AB  - The current paper makes an attempt to check whether the scintillation NaI(Tl)
      detectors, in spite of their poor energy resolution, can determine accurately the
      content of NORM in building materials. The activity concentrations of natural
      radionuclides were measured using two types of detectors: (a) NaI(Tl)
      spectrometer equipped with the special software based on the matrix method of
      least squares, and (b) high-purity germanium spectrometer. Synthetic compositions
      with activity concentrations varying in a wide range, from 1/5 to 5 times median
      activity concentrations of the natural radionuclides available in the earth crust
      and the samples of popular building materials, such as concrete, pumice and
      gypsum, were tested, while the density of the tested samples changed in a wide
      range (from 860 up to 2,410 kg/m(3)). The results obtained in the NaI(Tl) system
      were similar to those obtained with the HPGe spectrometer, mostly within the
      uncertainty range. This comparison shows that scintillation spectrometers
      equipped with a special software aimed to compensate for the lower spectral
      resolution of NaI(Tl) detectors can be successfully used for the radiation
      control of mass construction products.

PMID- 23542119
TI  - Characterization of non-tuberculosis mycobacteria by neutron radiography.
AB  - The genus Mycobacterium shares many characteristics with Corynebacterium and
      Actinomyces genera, among which the genomic guanine plus cytosine content and the
      production of long branched-chain fatty acids, known as mycolic acids are
      enhanced. Growth rate and optimal temperature of mycobacteria are variable. The
      genus comprises more than 140 known species; however Mycobacterium fortuitum, a
      fast growing nontuberculous mycobacterium, is clinically significant, because it
      has been associated to several lesions following surgery procedures such as
      liposuction, silicone breast and pacemaker implants, exposure to prosthetic
      materials besides sporadic lesions in the skin, soft tissues and rarely lungs.
      The objective of the present study is to reduce the time necessary for M.
      fortuitum characterization based on its morphology and the use of the neutron
      radiography technique substituting the classical biochemical assays. We also aim
      to confirm the utility of dendrimers as boron carriers. The samples were
      sterilized through conventional protocols using 10% formaldehyde. In the
      incubation process, two solutions with different molar ratios (10:1 and 20:1) of
      sodium borate and PAMAM G4 dendrimer and also pure sodium borate were used. After
      doping and sterilization procedures, the samples were deposited on CR-39 sheets,
      irradiated with a 4.6*10(5) n/cm(2)s thermal neutron flux for 30 min, from the J
      9 irradiation channel of the Argonauta IEN/CNEN reactor. The images registered in
      the CR-39 were visualized in a Nikon E400 optical transmission microscope and
      captured by a Nikon Coolpix 995 digital camera. Developing the nuclear tracks
      registered in the CR-39 allowed a 1000* enlargement of mycobacterium images,
      facilitating their characterization, the use of more sophisticated equipment not
      being necessary. The use of neutron radiography technique reduced the time
      necessary for characterization. Doping with PAMAM dendrimer improved the
      visualization of NTM in neutron radiography images.

PMID- 23542120
TI  - A rapid and inexpensive method for 226Ra and 228Ra measurements of high TDS
      groundwaters.
AB  - A series of laboratory-scale studies was conducted by preconcentrating (226)Ra
      from spiked water test samples using Purolite ion-exchange resin to evaluate the
      adsorption efficiency of the resin under varying conditions. After removing the
      resin from the columns, it was sealed in gas-tight containers and measured via
      gamma spectrometry. The Purolite resin showed high radium uptake and retention
      from natural waters in the presence of high iron and total dissolved solids
      (TDS). This procedure allowed us to process a large number of high TDS samples at
      a typical rate of 15 samples/day using three germanium detectors. Quality
      assurance and method validation have been achieved by analyzing selected
      groundwater samples, with different (226)Ra activities and high TDS values, and
      comparing the results to those using alpha spectrometry with a (133)Ba yield
      tracer. There was very good agreement between the obtained (226)Ra activities by
      both methods.

PMID- 23542121
TI  - Evaluation of three-dimensional polymer gel dosimetry using X-ray CT and R2 MRI.
AB  - It is difficult to obtain images of thin slices from measurement of spin-spin
      relaxation (R2) with magnetic resonance imaging (MRI) using the traditional dose
      reading method of polymer gel dosimetry. In this study, the dose reading method
      was performed using X-ray computed tomography (CT) for proton beam measurements
      in order to enable collection of thin slices. In addition, three-dimensional (3D)
      images of polymer gels were constructed using volume rendering. As a result of
      acquisition of thin slices, more detailed 3D data consisting of smaller voxel
      sizes compared to R2 were acquired. However, it was found that with thin slice
      thicknesses and small voxels, the signal-to-noise ratio around the voxels
      deteriorated. In addition, the coefficient of variation of non-irradiated gels
      with CT was smaller than that with R2 MRI.

PMID- 23542123
TI  - Record of the species of Tripartiella (Lom, 1959) from fishes of Manipur.
AB  - Survey on Trichodinid ciliophorans from the fresh water fishes of Manipur
      revealed three known species of the genus Tripartiella from the gills of major
      carps Labeo rohita (Hamilton); Cirrhinus mrigala (Hamilton); Catla catla and
      Ciprinus carpio. These are redescribed in this communication.

PMID- 23542122
TI  - A simple method of mouse lung intubation.
AB  - A simple procedure to intubate mice for pulmonary function measurements would
      have several advantages in longitudinal studies with limited numbers or expensive
      animal. One of the reasons that this is not done more routinely is that it is
      relatively difficult, despite there being several published studies that describe
      ways to achieve it. In this paper we demonstrate a procedure that eliminates one
      of the major hurdles associated with this intubation, that of visualizing the
      trachea during the entire time of intubation. The approach uses a 0.5 mm
      fiberoptic light source that serves as an introducer to direct the intubation
      cannula into the mouse trachea. We show that it is possible to use this procedure
      to measure lung mechanics in individual mice over a time course of at least
      several weeks. The technique can be set up with relatively little expense and
      expertise, and it can be routinely accomplished with relatively little training.
      This should make it possible for any laboratory to routinely carry out this
      intubation, thereby allowing longitudinal studies in individual mice, thereby
      minimizing the number of mice needed and increasing the statistical power by
      using each mouse as its own control.

PMID- 23542124
TI  - Mesentric cyst- an unusual presentation as inguinal hernia.
AB  - Mesenteric cyst is one of the uncommon childhood tumors. Mostly they are
      asymptomatic. Some of them present with non specific abdominal symptom like
      chronic abdominal pain very rarely they present as acute abdomen like torsion or
      intestinal obstruction. We are reporting a very rare presentation of Mesenteric
      cyst as an irreducible inguinal hernia.

PMID- 23542125
TI  - Volumetric measurement of vestibular schwannoma tumour growth following partial
      resection: predictors for recurrence.
AB  - Vestibular schwannomas (VS) have a higher risk of recurrence following subtotal
      resection than following near-total resection. We measured tumor remnant growth
      volumetrically in an attempt to determine potential predictors for postoperative
      recurrence following subtotal resection. We reviewed the charts of patients who
      had undergone VS surgery between 1998 and 2007. Thirty patients had an incomplete
      resection. The principal outcome measure was change in tumor volume (TV) on
      serial imaging. At a median follow-up of 6.8 years, volumetric measurements
      showed that 12 patients (40%) developed further tumor growth, while 18 patients
      remained with stable residual disease. The median rate of growth was 0.53
      cm(3)/year. Two-dimensional measurements confirmed growth in only eight of these
      patients. The postoperative residual TV correlated significantly with subsequent
      tumor growth (p = 0.038). All patients with residual volumes in excess of 2.5
      cm(3) exhibited recurrence. On univariate analysis, only postoperative TV was
      significantly associated with growth. Median time to failure was 21.5 months.
      This is the first report of volumetric measurements of VS tumor growth
      postoperatively. Volumetric measurements appear to be superior to two-dimensional
      measurements in documenting VS growth and patients with residual tumors >2.5
      cm(3) have a significantly higher rate of recurrence.

PMID- 23542126
TI  - Oxidative status in ICU patients with septic shock.
AB  - The aim of this pilot study was to investigate variability of oxidative stress
      during sepsis evolution. ICU patients with the diagnosis of septic shock were
      included. Thiobarbituric-acid reactive substances, total antioxidant capacity,
      protein carbonyls in plasma, reduced, oxidized glutathione and catalase activity
      in erythrocyte lysate were assessed in the 1st, 3rd, 5th and 8th day after sepsis
      appearance. A total of 17 patients were divided in two groups: survivors (n=7)
      and non-survivors (n=10). APACHE II was 11.5 +/- 5.4 and 19.9 +/- 4.97 in
      survivors and non-survivors respectively (p=0.005), while mean age and SOFA score
      at sepsis diagnosis, were similar between the two groups. GSH levels, catalase
      activity and protein carbonyls presented significant different course in time
      between survivors and non-survivors (p<0.05). Catalase activity was significantly
      higher in survivors (238.8 +/- 51.5) than non-survivors (166.4 +/- 40.2;
      p=0.005), while protein carbonyls levels were significantly lower in survivors
      (0.32 +/- 0.09) than non-survivors (0.48 +/- 0.16; p=0.036) on the 1st day. Yet,
      non-survivors exhibited a declining course in GSH levels during time, while GSH
      levels were maintained in survivors. Conclusively, a longstanding antioxidant
      deficiency in non-surviving patients was noted. This phenomenon was clearly
      prominent in patients' erythrocytes.

PMID- 23542127
TI  - HtrA2/Omi deficiency causes damage and mutation of mitochondrial DNA.
AB  - High-temperature requirement protein A2 (HtrA2), a serine protease, localizes in
      the mitochondria and has diverse roles, including maintenance of mitochondrial
      homeostasis and regulation of cellular apoptosis. HtrA2 (also known as Omi) is
      associated with many neurodegenerative diseases, including Parkinson disease. By
      employing agarose gel electrophoresis, a fluorescent dye, PicoGreen,
      intercalation into mtDNA, and long-range PCR (LR-PCR), we showed that
      mitochondrial DNA conformational stability is related to HtrA2. Nicked forms of
      mtDNA were produced through reactive oxygen species generated by loss of HtrA2
      protease activity, and mtDNA mutations frequently occurred in HtrA2(-/-) cells,
      but not in HtrA2(+/+) cells. We found conformational changes in mtDNA from the
      brain tissue of mnd2 mutant mice that lack the serine protease activity of HtrA2.
      Overexpression of HtrA2 with protease activity targeted to mitochondria only was
      able to restore mtDNA conformational stability in HtrA2(-/-) MEF cells. Nuclear
      encoded mtDNA repair genes, including POLG2, Twinkle, and APTX1, were
      significantly upregulated in HtrA2(-/-) cells. Electron microscopy showed that
      mitochondrial morphology itself was not affected, even in HtrA2(-/-) cells. Our
      results demonstrate that HtrA2 deficiency causes mtDNA damage through ROS
      generation and mutation, which may lead to mitochondrial dysfunction and
      consequent triggering of cell death in aging cells.

PMID- 23542128
TI  - The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis.
AB  - The voltage-dependent anion channel (VDAC), located at the outer mitochondria
      membrane (OMM), mediates interactions between mitochondria and other parts of the
      cell by transporting anions, cations, ATP, Ca(2+), and metabolites. Substantial
      evidence points to VDAC1 as being a key player in apoptosis, regulating the
      release of apoptogenic proteins from mitochondria, such as cytochrome c, and
      interacting with anti-apoptotic proteins. Recently, we demonstrated that VDAC1
      oligomerization is a general mechanism common to numerous apoptogens acting via
      different initiating cascades and proposed that a protein-conducting channel
      formed within a VDAC1 homo/hetero oligomer mediates cytochrome c release.
      However, the molecular mechanism responsible for VDAC1 oligomerization remains
      unclear. Several studies have shown that mitochondrial Ca(2+) is involved in
      apoptosis induction and that VDAC1 possesses Ca(2+)-binding sites and mediates
      Ca(2+) transport across the OMM. Here, the relationship between the cellular
      Ca(2+) level, [Ca(2+)]i, VDAC1 oligomerization and apoptosis was studied.
      Decreasing [Ca(2+)]i using the cell-permeable Ca(2+) chelating reagent BAPTA-AM
      was found to inhibit VDAC1 oligomerization and apoptosis, while increasing
      [Ca(2+)]i using Ca(2+) ionophore resulted in VDAC1 oligomerization and apoptosis
      induction in the absence of apoptotic stimuli. Moreover, induction of apoptosis
      elevated [Ca(2+)]i, concomitantly with VDAC1 oligomerization. AzRu-mediated
      inhibition of mitochondrial Ca(2+) transport decreased VDAC1 oligomerization,
      suggesting that mitochondrial Ca(2+) is required for VDAC1 oligomerization. In
      addition, increased [Ca(2+)]i levels up-regulate VDAC1 expression. These results
      suggest that Ca(2+) promotes VDAC1 oligomerization via activation of a yet
      unknown signaling pathway or by increasing VDAC1 expression, leading to
      apoptosis. This article is part of a Special Issue entitled: 12th European
      Symposium on Calcium.

PMID- 23542129
TI  - Dual roles for lysine 490 of promyelocytic leukemia protein in the
      transactivation of glucocorticoid receptor-interacting protein 1.
AB  - Glucocorticoid receptor-interacting protein 1 (GRIP1), a p160 family nuclear
      receptor co-activator protein, has three activation domains that recruit at least
      three secondary co-activators: CBP/p300, co-activator-associated arginine
      methyltransferase 1, and coiled-coil co-activator, which exhibits histone
      acetyltransferase and/or arginine methyltransferase activities. The regulatory
      mechanisms underlying the co-activation functions of GRIP1, which associates with
      promyelocytic leukemia protein (PML) in PML-nuclear bodies, are not well
      understood. This study showed that PML specifically and dramatically enhanced the
      C-terminal transactivation activity of GRIP1 by directly binding to GRIP1 but
      only when it was sumoylated. Most of the transactivation activity resided in the
      N-terminal PML regions that are conserved among isoforms. Three N-terminal
      sumoylation residues (Lys 65, 160, and 490) exhibited differential roles in the
      regulation of GRIP1 activity, and the sumoylation of Lys 490 acted as the primary
      nuclear localization signal of PML. While GRIP1 transactivation was stimulated to
      a similar degree by PML (K490R), located in the nucleus, and wild-type PML, PML
      (K490D) and the C-truncated mutant PML1-489 both displayed an epinuclear
      localization and were mostly inactive in stimulating GRIP. Based on these data,
      nuclear foci, nuclear localization, and the sumoylation status of Lys 490 were
      not essential for the enhancement of GRIP1 activity by PML, but the charge status
      of Lys 490 was important for subcellular localization of PML and cross-talk
      between its N- and C-terminal regions to modulate transcriptional activation.
      Taken together, these results provide insight into the regulatory mechanisms of
      PML that control the functional activities of GRIP1.

PMID- 23542130
TI  - Plasma TGF-beta1, MMP-1 and MMP-3 Levels in Chronic Pancreatitis.
AB  - Chronic pancreatitis (CP) presenting clinically with upper abdominal pain, as
      well as exocrine and endocrine insufficiencies, is characterized by irreversible
      morphological and functional alterations in the pancreas. The objective of the
      present study is to investigate the plasma levels of transforming growth factor
      beta 1 (TGF-beta1), matrix metalloproteinases MMP-1 (collagenase) and MMP-3
      (stromelysin) in CP. A total of 71 CP patients and 100 control subjects were
      considered for the study. Plasma levels of TGF-beta1, MMP-1 and MMP-3 were
      determined by enzyme-linked immunosorbent assay in patients and control subjects.
      The plasma levels of TGF-beta1 and MMP-1 were significantly elevated in patients
      compared to control group (*P = 0.0301, **P < 0.0001). However, there was no
      significant difference in the plasma levels of MMP-3 between patients and
      controls (P = 0.3756). The elevated levels of TGF-beta1 and MMP-1 may influence
      the inflammatory reactions by enhancing the pancreatic stellate cell activation
      and deposition of extracellular matrix resulting in pancreatic fibrosis. Thus,
      the present study highlights the role of fibrogenic cytokine marker TGF-beta1 and
      matrix metalloproteinases in the pathogenesis of CP.

PMID- 23542131
TI  - Harm avoidance in adolescents modulates late positive potentials during affective
      picture processing.
AB  - Research in adults has shown that individual differences in harm avoidance (HA)
      modulate electrophysiological responses to affective stimuli. To determine
      whether HA in adolescents modulates affective information processing, we
      collected event-related potentials from 70 adolescents while they viewed 90
      pictures from the Chinese affective picture system. Multiple regressions revealed
      that HA negatively predicted late positive potential (LPP) for positive pictures
      and positively predicted for negative pictures; however, HA did not correlate
      with LPP for neutral pictures. The results suggest that at the late evaluative
      stage, high-HA adolescents display attentional bias to negative pictures while
      low-HA adolescents display attentional bias to negative pictures. Moreover, these
      dissociable attentional patterns imply that individual differences in
      adolescents' HA modulate the late selective attention mechanism of affective
      information.

PMID- 23542132
TI  - Sequencing of the Dutch elm disease fungus genome using the Roche/454 GS-FLX
      Titanium System in a comparison of multiple genomics core facilities.
AB  - As part of the DNA Sequencing Research Group of the Association of Biomolecular
      Resource Facilities, we have tested the reproducibility of the Roche/454 GS-FLX
      Titanium System at five core facilities. Experience with the Roche/454 system
      ranged from <10 to >340 sequencing runs performed. All participating sites were
      supplied with an aliquot of a common DNA preparation and were requested to
      conduct sequencing at a common loading condition. The evaluation of sequencing
      yield and accuracy metrics was assessed at a single site. The study was conducted
      using a laboratory strain of the Dutch elm disease fungus Ophiostoma novo-ulmi
      strain H327, an ascomycete, vegetatively haploid fungus with an estimated genome
      size of 30-50 Mb. We show that the Titanium System is reproducible, with some
      variation detected in loading conditions, sequencing yield, and homopolymer
      length accuracy. We demonstrate that reads shorter than the theoretical minimum
      length are of lower overall quality and not simply truncated reads. The O. novo
      ulmi H327 genome assembly is 31.8 Mb and is comprised of eight chromosome-length
      linear scaffolds, a circular mitochondrial conti of 66.4 kb, and a putative 4.2
      kb linear plasmid. We estimate that the nuclear genome encodes 8613 protein
      coding genes, and the mitochondrion encodes 15 genes and 26 tRNAs.

PMID- 23542133
TI  - Otopathology in idiopathic Dandy's syndrome.
AB  - BACKGROUND: Dandy's syndrome, or bilateral vestibular hypofunction and
      oscillopsia, may cause chronic disequilibrium aggravated by head movement or in
      the presence of reduced light. It may be secondary to ototoxicity, central
      nervous system tumors, Meniere's syndrome, infections, or trauma or may be
      idiopathic. OBJECTIVE: To describe the temporal bone histopathology in one
      individual with idiopathic Dandy's syndrome. MATERIALS AND METHODS: Temporal
      bones from 1 individual were removed at autopsy and studied using light and
      Nomarski microscopy. RESULTS: In this case, the otopathology demonstrated
      vestibular atelectasis of the membranous labyrinth of the superior, lateral, and
      posterior semicircular canals but not the utricle or saccule bilaterally. The
      findings also included mild hair cell loss in the cristae of all semicircular
      canals and of the utricular and saccular maculae and severely reduced neuronal
      count in Scarpa's ganglion bilaterally. There was also a scattered loss of inner
      and outer hair cells throughout the cochlea and moderate-to-severe loss of
      cochlear neurons bilaterally. CONCLUSION: We have reported the histopathologic
      findings in a case of idiopathic Dandy's syndrome. Both temporal bones showed
      vestibular atelectasis of all three semicircular canals, preservation of normal
      saccule and utricle, and severe reduction of the neuronal population in Scarpa's
      ganglion bilaterally. Both ears also showed substantial degeneration of the
      spiral ganglion of the cochleas. Severe Scarpa's ganglion degeneration was also
      noted in the only other case of idiopathic Dandy's Syndrome in the literature.
      However, that other case had no evidence of vestibular atelectasis and had normal
      hearing.

PMID- 23542134
TI  - Reliability and validity of the Falls Efficacy Scale-International (FES-I) in
      individuals with dizziness and imbalance.
AB  - HYPOTHESIS: The purpose of this research is to establish the test-retest
      reliability and convergent validity of the Falls Efficacy Scale-International
      (FES-I) in people with vestibular disorders. BACKGROUND: Individuals with
      vestibular dysfunction have an increased risk of falling. The FES-I is a measure
      used to quantify an individual's concern of falling during different tasks.
      METHODS: A cross-sectional descriptive study was used to determine the test
      retest reliability and convergent validity of the FES-I. Fifty-three individuals
      with vestibular or balance dysfunction completed the FES-I twice during an
      initial evaluation by a neurotologist. Test-retest reliability was assessed using
      the intraclass correlation coefficient. The convergent validity was measured by
      correlating the FES-I with the Activities-Specific Balance Confidence (ABC)
      scale, Dizziness Handicap Inventory (DHI), Vestibular Activities and
      Participation (VAP) scale, 4-item Dynamic Gait Index (DGI-4), and measuring gait
      speed. RESULTS: The FES-I demonstrated high test-retest reliability (intraclass
      correlation coefficient, model 3,1: 0.94; 95% confidence interval, 0.90-0.97) and
      had concurrent validity with other self-report and physical performance measures
      (correlation coefficients for the ABC, -0.84; DHI, 0.75; VAP, 0.78; gait speed, 
      0.55; and DGI-4, -0.55). CONCLUSION: The FES-I is a reliable and valid tool for
      measuring an individual's concern of falling in a sample of people with
      vestibular disorders.

PMID- 23542135
TI  - Bicyclists overestimate their own night-time conspicuity and underestimate the
      benefits of retroreflective markers on the moveable joints.
AB  - Conspicuity limitations make bicycling at night dangerous. This experiment
      quantified bicyclists' estimates of the distance at which approaching drivers
      would first recognize them. Twenty five participants (including 13 bicyclists who
      rode at least once per week, and 12 who rode once per month or less) cycled in
      place on a closed-road circuit at night-time and indicated when they were
      confident that an approaching driver would first recognize that a bicyclist was
      present. Participants wore black clothing alone or together with a fluorescent
      bicycling vest, a fluorescent bicycling vest with additional retroreflective
      tape, or the fluorescent retroreflective vest plus ankle and knee reflectors in a
      modified 'biomotion' configuration. The bicycle had a light mounted on the
      handlebars which was either static, flashing or off. Participants judged that
      black clothing made them least visible, retroreflective strips on the legs in
      addition to a retroreflective vest made them most visible and that adding
      retroreflective materials to a fluorescent vest provides no conspicuity benefits.
      Flashing bicycle lights were associated with higher conspicuity than static
      lights. Additionally, occasional bicyclists judged themselves to be more visible
      than did frequent bicyclists. Overall, bicyclists overestimated their conspicuity
      compared to previously collected recognition distances and underestimated the
      conspicuity benefits of retroreflective markings on their ankles and knees.
      Participants mistakenly judged that a fluorescent vest that did not include
      retroreflective material would enhance their night-time conspicuity. These
      findings suggest that bicyclists have dangerous misconceptions concerning the
      magnitude of the night-time conspicuity problem and the potential value of
      conspicuity treatments.

PMID- 23542136
TI  - Systemic accident analysis: examining the gap between research and practice.
AB  - The systems approach is arguably the dominant concept within accident analysis
      research. Viewing accidents as a result of uncontrolled system interactions, it
      forms the theoretical basis of various systemic accident analysis (SAA) models
      and methods. Despite the proposed benefits of SAA, such as an improved
      description of accident causation, evidence within the scientific literature
      suggests that these techniques are not being used in practice and that a research
      practice gap exists. The aim of this study was to explore the issues stemming
      from research and practice which could hinder the awareness, adoption and usage
      of SAA. To achieve this, semi-structured interviews were conducted with 42 safety
      experts from ten countries and a variety of industries, including rail, aviation
      and maritime. This study suggests that the research-practice gap should be closed
      and efforts to bridge the gap should focus on ensuring that systemic methods meet
      the needs of practitioners and improving the communication of SAA research.

PMID- 23542137
TI  - Effects of oncological treatments on semen quality in patients with testicular
      neoplasia or lymphoproliferative disorders.
AB  - Pretherapy sperm cryopreservation in young men is currently included in good
      clinical practice guidelines for cancer patients. The aim of this paper is to
      outline the effects of different oncological treatments on semen quality in
      patients with testicular neoplasia or lymphoproliferative disorders, based on an
      8-year experience of the Cryopreservation Centre of a large public hospital. Two
      hundred and sixty-one patients with testicular neoplasia and 219 patients with
      lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and
      pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters
      (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone,
      inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after
      the end of cancer treatment. At the time of sperm collection, baseline FSH level
      and sperm concentration were impaired to a greater extent in patients with
      malignant testicular neoplasias than in patients with lymphoproliferative
      disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months
      after the end of cancer therapies, while an improvement of seminal parameters was
      observed after 18 months. In conclusion, an overall increase in sperm
      concentration was recorded about 18 months after the end of cancer treatments in
      the majority of patients, even if it was not possible to predict the evolution of
      each single case 'a priori'. For this reason, pretherapy semen cryopreservation
      should be considered in all young cancer patients.

PMID- 23542138
TI  - Three-dimensional mapping and comparative analysis of the distal human corpus
      cavernosum and the inflatable penile prosthesis.
AB  - The intricate anatomy of the corpus cavernosum in both the flaccid and tumescent
      state has not been fully elucidated. We report our experience using a three
      dimensional (3D) scanner to reconstruct cadaveric casts and compare them with 3D
      images of two prototypes of penile prosthesis. Two different models of the Titan
      Coloplast inflatable penile prosthesis were analyzed using a 3D scanner. The
      first was the standard model and the second was a newer model with a rounder
      silicone tip. Two cadaveric phalluses were harvested using Smooth-Cast 300Q
      polyurethane molding. The molds were excised and scanned along side the penile
      prosthesis. 3D scans were completed and analyzed using Leios Mesh software, and
      GOM Inspect software. The 3D scans demonstrated the mean human corporal radii 2
      mm from the distal tip to be 36.51 mm (36.01-37.0 mm), which is an obtuse angle.
      The standard Titan penile prosthesis spherical radius at the same level was
      202.52 mm, while the new silicone tip prosthesis had a radius of 139.33 mm. 3D
      mapping further demonstrated the trajectory of the cavernosa appeared curvilinear
      and the distal ends appeared blunt. The use of cadaveric cavernosal molds in
      combination with the 3D scanner allowed us to accurately image the corpus
      cavernosum for the first time. Our findings suggest that anatomically accurate
      corporal tips appear to be relatively blunt and that the new Titan silicone tip
      penile prosthesis more closely resembles the human corporal tip.

PMID- 23542139
TI  - Preliminary experimental study of urethral reconstruction with tissue engineering
      and RNA interference techniques.
AB  - This study investigated the feasibility of replacing urinary epithelial cells
      with oral keratinocytes and transforming growth factor-beta1 (TGF-beta1) small
      interfering RNA (siRNA)-transfected fibroblasts seeded on bladder acellular
      matrix graft (BAMG) in order to reconstruct tissue-engineered urethra.
      Constructed siRNAs, which expressed plasmids targeting TGF-beta1, were
      transfected into rabbit fibroblasts. The effective siRNA was screened out by RT
      PCR and was transfected into rabbit fibroblasts again. Synthesis of type I
      collagen in culture medium was measured by enzyme-linked immuno sorbent assay
      (ELISA). Autologous oral keratinocytes and TGF-beta1 siRNA-transfected
      fibroblasts were seeded onto BAMGs to obtain a tissue-engineered mucosa. The
      tissue-engineered mucosa was assessed morphologically and with the help of
      scanning electron microscopy. The TGF-beta1 siRNA decreased the expression of
      fibroblasts synthesis type I collagen. Oral keratinocytes and TGF-beta1 siRNA
      transfected fibroblasts were seeded onto sterilized BAMG to obtain a tissue
      engineered mucosa for urethral reconstruction. The compound graft was assessed
      using scanning electron microscope. Oral keratinocytes and TGF-beta1 siRNA
      transfected fibroblasts had a good compatibility with BAMG. The downregulation of
      fibroblasts synthesis type I collagen expression by constructed siRNA interfering
      TGF-beta1 provided a potential basis for genetic therapy of urethral scar. Oral
      keratinocytes and TGF-beta1 siRNA-transfected fibroblasts had good compatibility
      with BAMG and the compound graft could be a new choice for urethral
      reconstruction.

PMID- 23542140
TI  - The penile tourniquet.
AB  - Tourniquets are commonly used in penile surgery to achieve a bloodless operating
      field or produce artificial erections intraoperatively. Several techniques have
      been described, but there is a paucity of data and a lack of guidelines to direct
      their safe use. In penile surgery, it is the local rather than systemic effects
      of tourniquet use that are the main concern. Tourniquet time should be kept to a
      minimum, as the limited data available suggests that reperfusion injury can occur
      even after short periods of ischaemia. High risk groups such as diabetics and
      arteriopaths are at particular risk. Further studies are needed to determine safe
      tourniquet times and pressures.

PMID- 23542141
TI  - mRNA transfection-based, feeder-free, induced pluripotent stem cells derived from
      adipose tissue of a 50-year-old patient.
AB  - Induced pluripotent stem cells (iPSC) have successfully been derived from somatic
      fibroblasts through transfection of synthetic modified mRNA encoding
      transcription factors. This technique obviates the use of recombinant DNA and
      viral vectors in cellular reprogramming. The present study derived iPSC from
      adipose-derived mesenchymal stem cells (of a 50-year-old female patient) by
      utilizing a similar technique, but with defined culture medium without feeder
      cells, during both reprogramming and propagation. Clonal selection was performed
      to yield 12 putative iPSC lines from individual colonies of nascent reprogrammed
      cells, starting from 150,000 cells. However, only seven lines maintained their
      undifferentiated state after 10 continuous serial passages. These seven lines
      were then subjected to a rigorous battery of analyses to confirm their identity
      as iPSC. These tests included immunostaining, flow cytometry, qRT-PCR, in vitro
      differentiation assay, and teratoma formation assay within SCID mice. Positive
      results were consistently observed in all analyses, thus verifying the cells as
      fully reprogrammed iPSC. While all 7 iPSC lines displayed normal karyogram up to
      passage 13, chromosomal anomalies occurred in 4 of 7 lines with extended in vitro
      culture beyond 24 serial passages. Only three lines retained normal karyotype of
      46,XX. The remaining four lines displayed mosaicism of normal and abnormal
      karyotypes. Hence, this study successfully derived iPSC from abundant and easily
      accessible adipose tissues of a middle-aged patient; utilizing a mRNA-based
      integration-free technique under feeder-free conditions. This is a step forward
      in translating iPSC into personalized regenerative medicine within the clinic.

PMID- 23542142
TI  - Protective effects of fractions from Pseudostellaria heterophylla against cobalt
      chloride-induced hypoxic injury in H9c2 cell.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Except for as a well-known tonic Chinese herbal
      medicine for the treatment of splenic asthenia, anorexia, lassitude and weakness,
      the roots of Pseudostellaria heterophylla was also used in Chinese medicines for
      the treatment of palpitation. AIM OF THE STUDY: The study was designed to
      determine whether fractions from Pseudostellaria heterophylla could provide
      cardioprotection on hypoxic cardiomyocytes, what structural types of compounds
      were responsible for the observed effects, and which is the possible mechanism of
      action. MATERIALS AND METHODS: The roots of Pseudostellaria heterophylla were
      extracted successively with 70% aqueous ethanol and water to give a 70% ethanol
      extract and a water extract. The latter was first precipitated by 80% ethanol and
      then protein-removed by the Sevag method to give a fraction enriched in
      polysaccarides (PHP). The former was separated by column chromatography into a
      fraction enriched in small-molecule sugars and amino acids (PHSSAC), saponins
      (PHS), cyclopeptides (PHCP), and sapogenins (PHSG). UV spectral or chemical
      methods were used to confirm the five fractions. The cardioprotective effects of
      the fractions were evaluated by measuring the viability and the leakage of
      lactate dehydrogenase (LDH) of the fraction-pretreated cardiomyocyte H9c2 after
      exposure to CoCl2-induced hypoxia. The mechanism of action was studied by
      investigating the nature of cell death inhibition (by Annexin V/PI flow
      cytometric analysis) and their effects on the levels of malonaldehyde (MDA),
      superoxide dismutase (SOD) and intracellular reactive oxygen species (ROS).
      RESULTS: Fractions PHS and PHP could attenuate CoCl2-induced hypoxic damage to an
      extent higher than or comparable to the effect of the positive control N-acetyl-l
      cysteine (NAC). Pretreatment of the cells with 800 MUg/mL of PHS or 10mg/mL of
      PHP markedly decreased the level of MDA, reduced intracellular ROS, increased the
      activity of SOD, and reduced leakage of LDH to the levels close to or better than
      that with 326 MUg/mL of NAC. Reduction of apoptosis was also observed for both
      fractions. CONCLUSIONS: The overall results suggested that the traditional use of
      this plant for the treatment of palpitation may be attributed to the presence of
      cardioprotective agents in Pseudostellaria heterophylla. PHP and PHS were the two
      active fractions responsible for its cardioprotective effect. The mechanism might
      involve protections of the cell membrane from hypoxic damage and of the cells
      from oxidative injury via preventing increased oxidative stress. Protection of
      the cells via inhibition of cellular apoptosis may also be involved.

PMID- 23542143
TI  - The incorporation of Brazilian propolis into collagen-based dressing films
      improves dermal burn healing.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hydroalcoholic solutions of propolis, a resinous
      product produced by bees, have been currently employed in improving the
      cicatricial repair. Biological activity of propolis might be related to its
      antimicrobial, anti-inflammatory and immunomudalatory properties. AIM OF THIS
      STUDY: Investigate the suitability of the collagen-based films containing
      hydroalcoholic extracts of two different varieties of Brazilian propolis (green
      and red ones) on the dermal burn healing in rodent model. MATERIALS AND METHODS:
      The hydroalcoholic extracts of red propolis (RP) or Green propolis (GP) were
      incorporated into collagen-based dressing films (COL). Burn wounds were performed
      in the dorsum of Wistar rats and dressing with COL, COL+GPa (0.5%), COL+GPb
      (1,0%) or COL+RP (0.5%). A control group (CTR) was performed keeping the wound
      undressed. The histological analyses were carried out after 3, 7, 14, 21 and 30
      days for histological assessment of the inflammatory response, epithelization
      rates (ER), myofibroblastic count (MC) and collagenization pattern. RESULTS: GPa,
      GPb and RP provided significant decrease of the inflammatory severity, improved
      the ER in GPa in 7 (p=0.000), 14 (p=0.000), 21 (p=0.005) and 30 days (p=0.015),
      and induced earlier replacement of type-III for type-I collagen (p<0.05) than COL
      and CTR. In all the groups, the MC increased progressively from 3 to 14 days, and
      then started to decrease slowly until 21 days. Although no significant difference
      was observed among the groups in 3, 7 and 30 days, the MC was significantly
      increased in RP in 14 (p=0.0001) and 21 days (p=0.04), as well as grosser
      interlacement of the collagen bundles compared with the other groups. CONCLUSION:
      The incorporation of hydroalcoholic extracts of Brazilian propolis improved the
      biological events associated to burn healing without toxic effects, but the red
      variety provided the best results. Therefore, these collagen-based containing
      natural apicultural products films may be considered a promising new dressing for
      wound occlusion and tissue repairing.

PMID- 23542144
TI  - Isolation and characterization of an antibacterial biflavonoid from an African
      chewing stick Garcinia kola Heckel (Clusiaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The use of African chewing sticks in maintaining
      oral health is widely practiced in African countries. It has been reported that
      chewing stick users have a lower rate of dental caries and a better general oral
      health than non-users. It is generally thought that the beneficial effect of
      chewing stick is attributed to the mechanical cleansing effect and antimicrobial
      substances present in the stick. However, the active antimicrobial substances
      remain uncharacterized. AIM OF THE STUDY: To provide a scientific basis for the
      anti-caries effect of African chewing sticks, the authors purify an active
      antibacterial compound from Garcinia kola Heckel, a Nigerian chewing stick and
      examined the antibacterial activity of this compound against the cariogenic
      bacterium Streptococcus mutans. MATERIALS AND METHODS: Methanol extract was
      prepared from Garcinia kola and was further fractionated by solvent extractions.
      Silica gel chromatography was used to purify the antibacterial compound from the
      active fraction. The identity of the purified compound was determined by NMR
      analysis. The antibacterial activity of the purified compound was examined by
      standard microbiological assays. RESULTS: The antibacterial activity was found in
      the ether fraction and the active compound was isolated and determined to be a
      biflavonoid named GB1. GB1 was active against Streptococcus mutans and other oral
      bacteria with minimum inhibitory concentration (MIC) values of 32-64MUg/ml. The
      basis for the antibacterial effect of GB1 was investigated using Streptococcus
      mutans as the target. At 256MUg/ml, GB1 exhibited some bacteriocidal activity
      against Streptococcus mutans and induced the aggregation of Streptococcus mutans.
      GB1 has no apparent effects on protein synthesis and DNA synthesis but inhibited
      glucose uptake and utilization by Streptococcus mutans suggesting that GB1 exerts
      its antibacterial effect by inhibiting metabolism. GB1 also inhibited the
      formation of water-insoluble glucan by the extracellular glucosyltransferases
      from Streptococcus mutans in a dose-dependent manner. Streptococcus mutans did
      not develop resistance to GB1 upon subculturing in the presence of sub-MIC level
      of the biflavonoid. CONCLUSION: The antibacterial effect and glucan synthesis
      inhibition property of this biflavonoid may account for some of the beneficial
      effects reported in the chewing stick users.

PMID- 23542145
TI  - Tanshinone IIA, a constituent of Danshen, inhibits the release of glutamate in
      rat cerebrocortical nerve terminals.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a commonly used traditional Chinese
      medicine and has received considerable attention due to their beneficial effects
      on the health, including prevention of cardiovascular disease, and cancer.
      Tanshinone IIA, a major active constituent of Danshen, has been reported to have
      a neuroprotective profile. AIM OF THE STUDY: An excessive release of glutamate is
      considered to be related to neuropathology of several neurological diseases. In
      this study, we investigated whether tanshinone IIA could affect endogenous
      glutamate release and explored the possible mechanism. MATERIALS AND METHODS: The
      experimental model was the isolated nerve terminals (synaptosomes) purified from
      the rat cerebral cortex. The release of glutamate was evoked by the K(+) channel
      blocker 4-aminopyridine (4-AP) and measured by one-line enzyme-coupled
      fluorometric assay. We also used a membrane potential-sensitive dye to assay
      nerve terminal excitability and depolarization, and a Ca(2+) indicator, Fura-2
      acetoxymethyl ester, to monitor cytosolic Ca(2+) concentrations ([Ca(2+)]C).
      RESULTS: Tanshinone IIA inhibited the release of glutamate evoked by 4-AP in a
      concentration-dependent manner. Inhibition of glutamate release by tanshinone IIA
      was prevented by the chelating the extracellular Ca(2+) ions, and by the
      vesicular transporter inhibitor bafilomycin A1. However, the glutamate
      transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect
      on the action of tanshinone IIA. Tanshinone IIA decreased the depolarization
      induced increase in [Ca(2+)]C, whereas it did not alter the resting synaptosomal
      membrane potential or 4-AP-mediated depolarization. Furthermore, the effect of
      tanshinone IIA on evoked glutamate release was prevented by the Cav2.2 (N-type)
      and Cav2.1 (P/Q-type) channel blocker omega-conotoxin MVIIC, but not by the
      ryanodine receptor blocker dantrolene or the mitochondrial Na(+)/Ca(2+) exchanger
      blocker CGP37157. Mitogen-activated protein kinase (MEK) inhibition also
      prevented the inhibitory effect of tanshinone IIA on evoked glutamate release.
      CONCLUSION: These results show that tanshinone IIA inhibits glutamate release
      from cortical synaptosomes in rats through the suppression of presynaptic voltage
      dependent Ca(2+) entry and MEK signaling cascade.

PMID- 23542147
TI  - Ethanol extract of Adiantum capillus-veneris L. suppresses the production of
      inflammatory mediators by inhibiting NF-kappaB activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Adiantum capillus-veneris L. is a wildly
      distributed plant species and has been extensively used in south of China as
      traditional folk medicine for the treatment of inflammatory diseases. AIM OF THE
      STUDY: To investigate the anti-inflammatory effect of ethanolic extracts of
      Adiantum capillus-veneris L. and the involvement of NF-kappaB signaling in the
      regulation of inflammation. MATERIALS AND METHODS: The plant ethanolic extracts
      were initially tested against lipopolysaccharide (LPS)-induced prostaglandin E2
      (PGE2) production in RAW264.7 mouse macrophages, and interleukin 6 (IL-6) and
      tumor necrosis factor (TNF) production in human U937 monocytes. The effect of the
      plant extracts on the transcription factor nuclear factor kappa B (NF-kappaB)
      pathway was evaluated in TNF-alpha stimulated HepG2 cells by luciferase gene
      reporter assay and Western blotting at the transcriptional and translational
      levels. Subsequently, the inhibition of NF-kappaB downstream gene expression (IL
      8 and ICAM-1) by the plant extracts was assessed via quantitative real time
      polymerase chain reaction (qPCR). Lastly, the anti-inflammatory activities of the
      plant extracts in vivo were evaluated by testing spleen index and NF-kappaB
      related protein expression in LPS-stimulated CD1 mice. RESULTS: The plant
      ethanolic extracts effectively suppressed PGE2, IL-6 and TNF release with an IC50
      less than 50 MUg/ml. Moreover, luciferase expression could be specifically
      blocked in HepG2 cells, not in HEK293 cells, showing that the plant extracts
      displayed a cell-specific pattern on NF-kappaB gene transcription. The assayed
      biological activity also depended on the order of adding TNF-alpha and the plant
      extracts because the plant extracts could only block the NF-kappaB activation if
      added earlier but were unable to stop the signal when added after TNF-alpha.
      However, the plant extracts did not exert any effect on ubiquitination which
      regulates several steps in the NF-kappaB pathway. Additionally, the plant
      extracts down-regulated phosphorylation of IKKalpha/beta at S176/180, p38 at
      T180/Y182 and p65 at S536, but not p65 at S276. This was confirmed by their
      ability to selectively abrogate the induction of IL-8 transcription, whereas the
      ICAM-1 gene, which is not transcribed selectively by an NF-kappaB complex
      containing a form of p65 phosphorylated on Ser536, did not change. Finally, the
      plant extracts at 200 MUg/mg could normalize the LPS-induced elevation of spleen
      index as well as NF-kappaB and p38 activations in CD1 mice. CONCLUSION: The
      present studies presents the potential utilization of this plant extracts, as a
      natural resources for the development of an anti-inflammatory medicine.

PMID- 23542146
TI  - Antiplasmodial activity of sesquiterpene lactones and a sucrose ester from
      Vernonia guineensis Benth. (Asteraceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous preparations of Vernonia guineensis
      Benth. (Asteraceae) are used in Cameroonian folk medicine as a general stimulant
      and to treat various illnesses and conditions including malaria, bacterial
      infections and helminthic infestations. MATERIALS AND METHODS: Ten gram samples
      of the leaf and tuber powders of Vernonia guineensis were extracted separately
      using dichloromethane, methanol and distilled water. The extracts were dried in
      vacuo and used in bioassays. These extracts and three compounds previously
      isolated from Vernonia guineensis [vernopicrin (1), vernomelitensin (2) and
      pentaisovalerylsucrose (3)] were screened for antiplasmodial activity against
      chloroquine (CQ)-sensitive (Hb3) and CQ-resistant (Dd2) Plasmodium falciparum
      lines. RESULTS: Crude extracts and pure compounds from Vernonia guineensis showed
      antiplasmodial activity against both Hb3 and Dd2. The IC50 values of extracts
      ranged from 1.64 to 27.2 ug/ml for Hb3 and 1.82-30.0 ug/ml for Dd2; those for
      compounds 1, 2 and 3 ranged from 0.47 to 1.62 ug/ml (1364-1774 nM) for Hb3 and
      0.57-1.50 ug/ml (1644-2332nM) for Dd2. None of the crude extracts or pure
      compounds was observed to exert toxic effects on the erythrocytes used to
      cultivate the Plasmodium falciparum lines. CONCLUSION: In Cameroonian folk
      medicine, Vernonia guineensis may be used to treat malaria in part due to the
      antiplasmodial activity of sesquiterpene lactones (1, 2), a sucrose ester (3) and
      perhaps other compounds present in crude plant extracts. Exploring the safety and
      antiplasmodial efficacy of these compounds in vivo requires further study.

PMID- 23542148
TI  - Xiao-Qing-Long-Tang (Sho-seiryu-to) inhibited cytopathic effect of human
      respiratory syncytial virus in cell lines of human respiratory tract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-Qing-Long-Tang (XQLT, TJ-19, Sho-seiryu-to,
      so-cheong-ryong-tang) has been used against acute airway diseases for thousands
      of year in ancient China. Most of the acute airway illnesses are caused by virus.
      However, without activity against influenza virus, XQLT has been questioned to
      manage respiratory tract viral infection. Nevertheless, XQLT might be active
      against airway viruses other than influenza. Human respiratory syncytial virus
      (HRSV) is one of the most common respiratory viral pathogens without effective
      management. However, it is unknown whether XQLT has anti-HRSV activity. AIM OF
      THE STUDY: We tested the hypothesis that XQLT can effectively minimize HRSV
      induced plaque formation in respiratory tract mucosal cell lines. MATERIALS AND
      METHODS: Anti-HRSV activity of a hot water extract of XQLT was examined by plaque
      reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell
      lines. Its effects on syncytial formation and viral fusion (F) protein were
      examined directly by microscopy and by western blot, respectively. Ability of
      XQLT to stimulate IFN-beta was evaluated by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Hot water extract of XQLT dose-dependently inhibited HRSV
      induced plaque formation in both HEp-2 and A549 cells (P<0.0001), particularly
      when given before viral inoculation (p<0.0001). XQLT inhibited viral attachment
      (p<0.0001) and internalization (p<0.0001). 300MUg/ml XQLT could decrease both the
      number and the size of HRSV-induced syncytium without clear effect on the
      production of viral F protein. XQLT could stimulate epithelial cells to secrete
      IFN-beta before and after viral inoculation to counteract viral infection
      (p<0.0001). CONCLUSIONS: XQLT is effective against HRSV infection on airway
      epithelia by preventing viral attachment, internalization, syncytial formation,
      and by stimulating interferon secretion.

PMID- 23542152
TI  - Inter and intraspecific variation in female remating propensity in the
      cactophilic sibling species Drosophila buzzatii and D. koepferae.
AB  - Post-mating sexual selection by means of sperm competition or cryptic female
      choice occurs in species in which females remate before exhausting sperm supplied
      by previous mates. Thus, sperm competition is expected to be stronger when
      inseminated females remate more frequently or take longer to deplete sperm load.
      Previous studies comparing oviposition behavior in the pair of closely related
      species Drosophila buzzatii and Drosophila koepferae suggest that inseminated
      females of the latter deplete sperm load more rapidly. Here, we investigate
      female remating in D. buzzatii and D. koepferae by studying how female remating
      propensity changes after mating. Our study reveals that, after mating, female D.
      buzzatii recovers receptivity 14 times faster and remate more frequently than D.
      koepferae. Thus, we argue that D. buzzatii exhibits greater chances that sperm
      from different mates meet inside the same female suggesting more complex post
      mating interactions than in its sibling. In addition, our results show that there
      is intraspecific genetic variation for the duration of female refractory period
      in both species.

PMID- 23542149
TI  - Unraveling root developmental programs initiated by beneficial Pseudomonas spp.
      bacteria.
AB  - Plant roots are colonized by an immense number of microbes, referred to as the
      root microbiome. Selected strains of beneficial soil-borne bacteria can protect
      against abiotic stress and prime the plant immune system against a broad range of
      pathogens. Pseudomonas spp. rhizobacteria represent one of the most abundant
      genera of the root microbiome. Here, by employing a germ-free experimental
      system, we demonstrate the ability of selected Pseudomonas spp. strains to
      promote plant growth and drive developmental plasticity in the roots of
      Arabidopsis (Arabidopsis thaliana) by inhibiting primary root elongation and
      promoting lateral root and root hair formation. By studying cell type-specific
      developmental markers and employing genetic and pharmacological approaches, we
      demonstrate the crucial role of auxin signaling and transport in rhizobacteria
      stimulated changes in the root system architecture of Arabidopsis. We further
      show that Pseudomonas spp.-elicited alterations in root morphology and
      rhizobacteria-mediated systemic immunity are mediated by distinct signaling
      pathways. This study sheds new light on the ability of soil-borne beneficial
      bacteria to interfere with postembryonic root developmental programs.

PMID- 23542150
TI  - Patatin-related phospholipase pPLAIIIdelta increases seed oil content with long
      chain fatty acids in Arabidopsis.
AB  - The release of fatty acids from membrane lipids has been implicated in various
      metabolic and physiological processes, but in many cases, the enzymes involved
      and their functions in plants remain unclear. Patatin-related phospholipase As
      (pPLAs) constitute a major family of acyl-hydrolyzing enzymes in plants. Here, we
      show that pPLAIIIdelta promotes the production of triacylglycerols with 20- and
      22-carbon fatty acids in Arabidopsis (Arabidopsis thaliana). Of the four pPLAIIIs
      (alpha, beta, gamma, delta), only pPLAIIIdelta gene knockout results in a
      decrease in seed oil content, and pPLAIIIdelta is most highly expressed in
      developing embryos. The overexpression of pPLAIIIdelta increases the content of
      triacylglycerol and 20- and 22-carbon fatty acids in seeds with a corresponding
      decrease in 18-carbon fatty acids. Several genes in the glycerolipid biosynthetic
      pathways are up-regulated in pPLAIIIdelta-overexpressing siliques. pPLAIIIdelta
      hydrolyzes phosphatidylcholine and also acyl-coenzyme A to release fatty acids.
      pPLAIIIdelta-overexpressing plants have a lower level, whereas pPLAIIIdelta
      knockout plants have a higher level, of acyl-coenzyme A than the wild type.
      Whereas seed yield decreases in transgenic plants that ubiquitously overexpress
      pPLAIIIdelta, seed-specific overexpression of pPLAIIIdelta increases seed oil
      content without any detrimental effect on overall seed yield. These results
      indicate that pPLAIIIdelta-mediated phospholipid turnover plays a role in fatty
      acid remodeling and glycerolipid production.

PMID- 23542151
TI  - The initiation of epigenetic silencing of active transposable elements is
      triggered by RDR6 and 21-22 nucleotide small interfering RNAs.
AB  - Transposable elements (TEs) are mobile fragments of DNA that are repressed in
      both plant and animal genomes through the epigenetic inheritance of repressed
      chromatin and expression states. The epigenetic silencing of TEs in plants is
      mediated by a process of RNA-directed DNA methylation (RdDM). Two pathways of
      RdDM have been identified: RNA Polymerase IV (Pol IV)-RdDM, which has been shown
      to be responsible for the de novo initiation, corrective reestablishment, and
      epigenetic maintenance of TE and/or transgene silencing; and RNA-dependent RNA
      Polymerase6 (RDR6)-RdDM, which was recently identified as necessary for
      maintaining repression for a few TEs. We have further characterized RDR6-RdDM
      using a genome-wide search to identify TEs that generate RDR6-dependent small
      interfering RNAs. We have determined that TEs only produce RDR6-dependent small
      interfering RNAs when transcriptionally active, and we have experimentally
      identified two TE subfamilies as direct targets of RDR6-RdDM. We used these TEs
      to test the function of RDR6-RdDM in assays for the de novo initiation,
      corrective reestablishment, and maintenance of TE silencing. We found that RDR6
      RdDM plays no role in maintaining TE silencing. Rather, we found that RDR6 and
      Pol IV are two independent entry points into RdDM and epigenetic silencing that
      perform distinct functions in the silencing of TEs: Pol IV-RdDM functions to
      maintain TE silencing and to initiate silencing in an RNA Polymerase II
      expression-independent manner, while RDR6-RdDM functions to recognize active
      Polymerase II-derived TE mRNA transcripts to both trigger and correctively
      reestablish TE methylation and epigenetic silencing.

PMID- 23542154
TI  - Dynamics of translation by single ribosomes through mRNA secondary structures.
AB  - During protein synthesis, the ribosome translates nucleotide triplets in single
      stranded mRNA into polypeptide sequences. Strong downstream mRNA secondary
      structures, which must be unfolded for translation, can slow or even halt protein
      synthesis. Here we used single-molecule fluorescence resonance energy transfer to
      determine reaction rates for specific steps within the elongation cycle as the
      Escherichia coli ribosome encounters stem-loop or pseudoknot mRNA secondary
      structures. Downstream stem-loops containing 100% GC base pairs decrease the
      rates of both tRNA translocation within the ribosome and deacylated tRNA
      dissociation from the ribosomal exit site (E site). Downstream stem-loops or
      pseudoknots containing both GC and AU pairs also decrease the rate of tRNA
      dissociation, but they have little effect on tRNA translocation rate. Thus,
      somewhat unexpectedly, unfolding of mRNA secondary structures is more closely
      coupled to E-site tRNA dissociation than to tRNA translocation.

PMID- 23542153
TI  - The structural basis for specific decoding of AUA by isoleucine tRNA on the
      ribosome.
AB  - Decoding of the AUA isoleucine codon in bacteria and archaea requires
      modification of a C in the anticodon wobble position of the isoleucine tRNA.
      Here, we report the crystal structure of the archaeal tRNA2(Ile), which contains
      the modification agmatidine in its anticodon, in complex with the AUA codon on
      the 70S ribosome. The structure illustrates how agmatidine confers codon
      specificity for AUA over AUG.

PMID- 23542155
TI  - Human inactive X chromosome is compacted through a PRC2-independent SMCHD1-HBiX1
      pathway.
AB  - Human inactive X chromosome (Xi) forms a compact structure called the Barr body,
      which is enriched in repressive histone modifications such as trimethylation of
      histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). These two histone marks are
      distributed in distinct domains, and X-inactive specific transcript (XIST)
      preferentially colocalizes with H3K27me3 domains. Here we show that Xi compaction
      requires HBiX1, a heterochromatin protein 1 (HP1)-binding protein, and structural
      maintenance of chromosomes hinge domain-containing protein 1 (SMCHD1), both of
      which are enriched throughout the Xi chromosome. HBiX1 localization to H3K9me3
      and XIST-associated H3K27me3 (XIST-H3K27me3) domains was mediated through
      interactions with HP1 and SMCHD1, respectively. Furthermore, HBiX1 was required
      for SMCHD1 localization to H3K9me3 domains. Depletion of HBiX1 or SMCHD1, but not
      Polycomb repressive complex 2 (PRC2), resulted in Xi decompaction, similarly to
      XIST depletion. Thus, the molecular network involving HBiX1 and SMCHD1 links the
      H3K9me3 and XIST-H3K27me3 domains to organize the compact Xi structure.

PMID- 23542157
TI  - Physiological changes associated with de qi during electroacupuncture to LI4 and
      LI11: a randomised, placebo-controlled trial.
AB  - BACKGROUND: Studies on the relationship between de qi intensity and activity
      changes in the autonomic nervous system (ANS) are scarce. This study investigates
      the physiological responses associated with de qi. The relationship between de qi
      intensity and such responses was determined. METHOD: This was a single-blinded,
      randomised, placebo-controlled trial. A total of 36 subjects (19 men, 17 women),
      aged 34.5+/-4.6 years, were randomly assigned to group 1 (electroacupuncture at 2
      Hz, 0.4 ms to right LI4 and LI11 for 30 min), group 2 (electroacupuncture
      stimulation to bilateral patellae) or group 3 (sham electroacupuncture to right
      LI4 and LI11 but over Duoderm pads). Heart rate (HR), mean arterial blood
      pressure (MAP) and HR variability by low/high frequency (LF/HF) were recorded 5
      min before, during and 5 min after the intervention. Needle sensations were
      quantified by the Modified Massachusetts General Hospital Acupuncture Sensation
      Scale - Chinese version (C-MMASS) and the C-MMASS index was computed. RESULTS: A
      significant increase in LF/HF, MAP and HR was observed in group 1. A small and
      significant increase in LF/HF was observed in group 2 but the changes in MAP and
      HR in groups 2 and 3 were not significant. The C-MMASS index was highest in group
      1 (5.3+/-1.3), moderate in group 2 (3.5+/-0.7) and lowest in group 3 (0.77+/
      0.2). A positive correlation between de qi intensity and changes in LF/HF, MAP
      and HR was observed. CONCLUSIONS: This study suggests that de qi is associated
      with physiological changes, and that de qi intensity increases with an increase
      in sympathetic discharge of the ANS.

PMID- 23542156
TI  - Energetic role of the paddle motif in voltage gating of Shaker K(+) channels.
AB  - Voltage-gated ion channels underlie rapid electric signaling in excitable cells.
      Electrophysiological studies have established that the N-terminal half of the
      fourth transmembrane segment ((NT)S4) of these channels is the primary voltage
      sensor, whereas crystallographic studies have shown that (NT)S4 is not located
      within a proteinaceous pore. Rather, (NT)S4 and the C-terminal half of S3 ((CT)S3
      or S3b) form a helix-turn-helix motif, termed the voltage-sensor paddle. This
      unexpected structural finding raises two fundamental questions: does the paddle
      motif also exist in voltage-gated channels in a biological membrane, and, if so,
      what is its function in voltage gating? Here, we provide evidence that the paddle
      motif exists in the open state of Drosophila Shaker voltage-gated K(+) channels
      expressed in Xenopus oocytes and that (CT)S3 acts as an extracellular hydrophobic
      'stabilizer' for (NT)S4, thus biasing the gating chemical equilibrium toward the
      open state.

PMID- 23542158
TI  - The relationship between gamma-glutamyl transferase levels and the clinical
      outcomes in patients with ST-segment elevation myocardial infarction undergoing
      primary percutaneous coronary intervention.
AB  - OBJECTIVES: Serum gamma-glutamyl transferase (GGT) activity has been shown to be
      related to the development of atherosclerosis and cardiovascular events. The aim
      of this study was to evaluate the prognostic value of GGT in patients with ST
      segment elevation myocardial infarction (STEMI) undergoing a primary percutaneous
      coronary intervention (PCI). PATIENTS AND METHODS: A total of 683 consecutive
      patients with STEMI who underwent primary PCI were evaluated. The study
      population was divided into tertiles on the basis of admission GGT values. A high
      GGT (n=221) was defined as a value in the upper third tertile (GGT>37) and a low
      GGT (n=462) was defined as any value in the lower two tertiles (GGT<=37). The
      mean follow-up time was 29 months. RESULTS: The in-hospital mortality rate was
      significantly higher in patients in the high GGT group (7.2 vs. 1.7%, P<0.001),
      as was the rate of adverse outcomes in patients with high GGT levels. In
      multivariate analyses, a significant association was found between high GGT
      levels and adjusted risk of in-hospital cardiovascular mortality (odds ratio=8.6,
      95% confidence interval: 2.3-32.4, P=0.001). In a receiver operating
      characteristic curve analysis, a GGT value greater than 37 was identified as an
      effective cutoff point in STEMI for in-hospital cardiovascular mortality (area
      under curve=0.71, 95% confidence interval: 0.59-0.82, P<0.001). There were no
      differences in the long-term adverse outcome rates between the two groups.
      CONCLUSION: GGT is a readily available clinical laboratory value associated with
      in-hospital adverse outcomes in patients with STEMI who undergo primary PCI.
      However, there was no association with long-term mortality.

PMID- 23542159
TI  - Mean platelet volume is associated with poor postinterventional myocardial blush
      grade in patients with ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: In a significant proportion of patients with ST-elevation myocardial
      infarction (STEMI), microvascular and myocardial reperfusion cannot be regained
      despite successfully restored thrombolysis in myocardial infarction (TIMI) grade
      3 epicardial blood flow. Myocardial blush grade (MBG) is a reliable marker for
      microvascular patency and predicts short-term and long-term mortality after
      primary percutaneous coronary intervention (PCI) in patients with acute STEMI,
      independent of other variables. Mean platelet volume (MPV), a unique measure of
      platelet size, is an indicator of platelet reactivity. In this study, we aimed to
      investigate the relation of admission MPV with postinterventional MBG in patients
      with STEMI and TIMI grade 3 flow at infarct artery after primary PCI. MATERIALS
      AND METHODS: Three hundred and ten patients were selected as a study group among
      patients with STEMI and TIMI grade 3 epicardial blood flow after primary PCI.
      Blood samples for analysis were obtained during the initial evaluation of
      patients at the emergency department. MBGs of patients were classified at the end
      of angioplasty. Patients with MBG 0 and 1 were defined as having poor myocardial
      blush and patients with MBG 2 and 3 were defined as having normal myocardial
      blush. RESULTS: Patients with poor myocardial blush had higher admission MPV
      (10.5+/-1.3 to 9.1+/-1 fl, P<0.001), higher peak creatine kinase myocardial band
      isoenzyme levels (260+/-53 to 190+/-38 U/l, P<0.001), higher white blood cell
      count (11.3+/-4 to 10.3+/-3*10/MUl, P=0.012), and lower left ventricular ejection
      fraction (42+/-7 to 51+/-8%, P<0.001) compared with patients with normal
      myocardial blush. Linear regression analysis showed that admission MPV was
      significantly associated with postinterventional MBG (coefficient=0.598,
      P<0.001). Cardiovascular mortality (13-5%, P=0.013) and acute-subacute stent
      thrombosis at 3 months (12-8%, P=0.028) were significantly higher in patients
      with poor postinterventional myocardial blush compared with those with normal
      myocardial blush. CONCLUSION: The MPV measured at admission is significantly
      associated with poor postinterventional MBG in patients with STEMI and TIMI grade
      3 flow at infarct artery after primary PCI.

PMID- 23542160
TI  - Angiogenesis imaging in myocardial infarction using 68Ga-NOTA-RGD PET:
      characterization and application to therapeutic efficacy monitoring in rats.
AB  - OBJECTIVE: Ga-NOTA-RGD PET is a newly developed molecular imaging for
      angiogenesis. In this study, Ga-NOTA-RGD PET was used to investigate imaging
      characteristics in a rat myocardial infarction (MI) model and to monitor the
      efficacy of an angiogenesis induction therapy. MATERIALS AND METHODS: Ga-NOTA-RGD
      PET was performed serially in rats with MI or sham operation, and myocardial
      uptake was analyzed with respect to time duration and tissue characteristics.
      Subsequently, Ga-NOTA-RGD PET was serially performed for therapeutic efficacy
      monitoring in MI-induced rats, which were treated with basic fibroblast growth
      factor (bFGF) injection or saline injection. Image findings were compared with
      the final change in MI lesion. RESULTS: Ga-NOTA-RGD uptake was significantly
      increased in MI lesion and gradually decreased over time. Ga-NOTA-RGD uptake in
      the infarcted tissue corresponded with vascular endothelial growth factor
      expression and macrophage accumulation. In monitoring of therapeutic efficacy,
      the lesion uptake in the bFGF-injected group was significantly higher than that
      of the saline-injected and sham-operated groups on the first day. However, no
      significant differences were observed between bFGF and saline-injected groups at
      subsequent time points, corresponding to the final infarct size change.
      CONCLUSION: Ga-NOTA-RGD PET would be a useful angiogenesis imaging modality in MI
      for assessment of pathophysiology or monitoring of therapeutic efficacy.

PMID- 23542161
TI  - Use of multiparameter evidence synthesis to assess the appropriateness of data
      and structure in decision models.
AB  - OBJECTIVES: Decision models for health technology appraisal are defined by their
      structure and data. Often there are alternatives for how the model might be
      specified and what data to include, and criteria are required to guide these
      choices. This study uses multiparameter evidence synthesis (MPES) to synthesize
      data from diverse sources and test alternative model structures. The methods are
      illustrated by a comparison of blood ketone testing versus urine ketone testing
      for young people with Type 1 diabetes. METHODS: Two approaches were compared. A
      simple statistical model (Model 1) was used to estimate the difference in the
      rates of adverse events from the outcome data of a randomized controlled trial
      (RCT). MPES (Model 2) was constructed to synthesize data on outcome and process
      variables from the RCT with data from nonrandomized studies on specificity and
      sensitivity. Sensitivity analyses were carried out using alternative model
      specifications for the MPES, and the consistency of the data was evaluated.
      RESULTS: Model 1 estimated that the mean difference in the rate of adverse events
      per day was 0.0011 (95% confidence interval 0.0005-0.00229) lower with blood
      ketone testing. Model 2 estimated a similar outcome but also estimated parameters
      for which there were no direct data, including the prevalence of high ketone
      levels and the sensitivity and specificity of the tests as used in the home.
      CONCLUSIONS: Model 1, which used only outcome data from an RCT, showed that blood
      ketone testing is more effective but did not explain why this is so. Model 2,
      estimated by MPES, suggested that the blood test is more accurate and that
      patients are more likely to comply with the protocol.

PMID- 23542162
TI  - Significant changes in mitochondrial distribution in different pain models of
      mice.
AB  - Mitochondria play an important role in pathophysiology of inflammatory and
      neuropathic pain but the mechanism is unclear. So far no comprehensive study
      exists that evaluates the changes of mitochondrial dynamics following the pain.
      In this study, we detected the mitochondrial distribution and subcellular
      morphology by using intrathecal injection of mitochondrial marker, Mitotracker
      Red(r) CM-H2XRox (Mito-Red) and confocal microscopic analysis in models of
      formalin-induced acute inflammatory pain, Complete Freund's Adjuvant (CFA)
      induced persistent pain and spared nerve injury (SNI)-induced neuropathic pain.
      The results demonstrated that subcutaneous formalin injection did not affect the
      number of Mito-Red cells within the spinal dorsal horn at both acute and tonic
      phases, but significantly increased the number of cluster type mitochondria in
      superficial spinal dorsal horn (laminas I-II) at tonic phase. Differently, the
      number of Mito-Red cells significantly increased in superficial and deep spinal
      dorsal horn (laminas III-V) following persistent CFA and SNI neuropathic pain.
      Moreover, both CFA and SNI remarkably increased the number of cluster type
      mitochondria and decreased the number of granule type mitochondria, in both
      superficial and deep spinal dorsal horn. So we concluded that abnormal
      mitochondrial distribution contributes to neuropathic and some forms of
      inflammatory pain.

PMID- 23542163
TI  - Behavioral and metabolic characterization of heterozygous and homozygous POLG
      mutator mice.
AB  - The mitochondrial DNA (mtDNA) polymerase gamma (POLG) mutator mice provide the
      first experimental evidence that high levels of somatic mtDNA mutations can be
      functionally significant. Here we report that older homozygous, but not
      heterozygous, POLG mice show significant reductions in striatal dopaminergic
      terminals as well as deficits in motor function. However, resting oxygen
      consumption, heat production, mtDNA content and mitochondrial electron transport
      chain activities are significantly decreased at older ages in both homozygous and
      heterozygous mice. These results indicate that high levels of somatic mtDNA
      mutations can contribute to dopaminergic dysfunction and to behavioral and
      metabolic deficits.

PMID- 23542165
TI  - The mismatch-negativity (MMN) component of the auditory event-related potential
      to violations of abstract regularities: a review.
AB  - The mismatch-negativity (MMN) component of the event-related potential (ERP) has
      been extensively used to study the preattentive processing and storage of
      regularities in basic physical stimulus features (e.g., frequency, intensity,
      spatial location). However, studies reviewed in the present article reveal that
      the auditory analysis reflected by MMN also includes the detection and use of
      more complex, "abstract", regularities based, for example, on relationships
      between various physical features of the stimuli or in patterns present in the
      auditory stream. When these regularities are violated, then MMN is elicited.
      Thus, the central auditory system performs even at the pre-attentive, auditory
      cortex level surprisingly "cognitive" operations, such as generalization leading
      to simple concept formation, rule extraction and prediction of future stimuli.
      The information extracted often seems to be in an implicit form, not directly
      available to conscious processes and difficult to express verbally. It can
      nevertheless influence the behavior of the subject, for example, the regularity
      violations can temporarily impair performance in the primary task. Neural,
      behavioral and cognitive events associated with the development of the regularity
      representations are discussed.

PMID- 23542164
TI  - Sterol regulatory element-binding proteins are regulators of the NIS gene in
      thyroid cells.
AB  - The uptake of iodide into the thyroid, an essential step in thyroid hormone
      synthesis, is an active process mediated by the sodium-iodide symporter (NIS).
      Despite its strong dependence on TSH, the master regulator of the thyroid, the
      NIS gene was also reported to be regulated by non-TSH signaling pathways. In the
      present study we provide evidence that the rat NIS gene is subject to regulation
      by sterol regulatory element-binding proteins (SREBPs), which were initially
      identified as master transcriptional regulators of lipid biosynthesis and uptake.
      Studies in FRTL-5 thyrocytes revealed that TSH stimulates expression and
      maturation of SREBPs and expression of classical SREBP target genes involved in
      lipid biosynthesis and uptake. Almost identical effects were observed when the
      cAMP agonist forskolin was used instead of TSH. In TSH receptor-deficient mice,
      in which TSH/cAMP-dependent gene regulation is blocked, the expression of SREBP
      isoforms in the thyroid was markedly reduced when compared with wild-type mice.
      Sterol-mediated inhibition of SREBP maturation and/or RNA interference-mediated
      knockdown of SREBPs reduced expression of NIS and NIS-specific iodide uptake in
      FRTL-5 cells. Conversely, overexpression of active SREBPs caused a strong
      activation of the 5'-flanking region of the rat NIS gene mediated by binding to a
      functional SREBP binding site located in the 5'-untranslated region of the rat
      NIS gene. These findings show that TSH acts as a regulator of SREBP expression
      and maturation in thyroid epithelial cells and that SREBPs are novel
      transcriptional regulators of NIS.

PMID- 23542166
TI  - Structure-activity relationship of 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin
      4-yl)-1H-indole analogues as 5-HT(6) receptor agonists.
AB  - To further investigate the structure-activity relationship (SAR) of the 5
      hydroxytryptamine type 6 (5-HT6) receptor agonist 5-chloro-2-methyl-3-(1,2,3,6
      tetrahydropyridin-4-yl)-1H-indole (EMD386088, 6), a series of 2-methyl-3-(1,2,3,6
      tetrahydropyridin-4-yl)-1H-indoles were synthesized, and in vitro affinity to,
      and functional activity at 5-HT6 receptors was tested. We focused on substituents
      made at the indole N(1)-, 2- and 5-positions and these were found to not only
      influence the affinity at 5-HT6 receptors but also the intrinsic activity leading
      to antagonists, partial agonists and full agonists. In order for a compound to
      demonstrate potent 5-HT6 receptor agonist properties, the indole N(1) should be
      unsubstituted, an alkyl group such as 2-methyl is needed and finally halogen
      substituents in the indole 5-position (fluoro, chloro or, bromo) were essential
      requirements. However, the introduction of a benzenesulfonyl group at N(1)
      position switched the full agonist 6 to be a 5-HT6 receptor antagonist (30). A
      few compounds within the 2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles
      were also screened for off-targets and generally they displayed low affinity for
      other 5-HT subtypes and serotonin transporter protein (SERT).

PMID- 23542167
TI  - RF: a method for filtering short reads with tandem repeats for genome mapping.
AB  - Next-generation sequencing platforms generate short (50-150bp) reads that can be
      mapped onto the reference genome. Repetitive sequences in the genome, because of
      the presence of similar or identical sequences, cause mapping errors in the case
      of the short reads. By filtering short reads with repeats, mapping will be
      improved. I developed RF. RF is a new method that filters short reads with tandem
      repeats. A scoring scheme was developed that assigned higher scores to regions
      with tandem repeats and lower scores to regions without tandem repeats. In this
      study, RF was applied to filter out short reads with repeats, before short reads
      were mapped onto the same genomic contig by using a short read-mapping program.
      The result suggests RF improved the proportion of correctly mapped short reads on
      filtering the repeats. RF is a useful tool for reducing mapping errors of short
      reads onto reference genomes.

PMID- 23542168
TI  - The development of metabolic risk factors after the initiation of the second line
      anti- retroviral therapy.
AB  - BACKGROUND AND OBJECTIVE: A Highly Active Anti-Retroviral Therapy (HAART) is
      accompanied with several metabolic effects like adipose redistribution and
      insulin resistance. In this study, we evaluated the association between a HAART
      and lipodystrophy. METHODS: A cross sectional study, whose subjects were Human
      Immunodeficiency Virus (HIV) infected patients, was conducted at a tertiary care
      hospital in south India. Among these, 27 were on protease inhibitors for at-least
      6 months and 13 were drug naive patients. The assessments of lipodystrophy,
      fasting blood sugar and the fasting lipid profile were done and these parameters
      were compared in the two groups. RESULTS: The analysis of the data which was
      collected, showed an elevation in the total cholesterol levels in the individuals
      who were on the protease inhibitors versus the drug naive patients. There was a
      significant elevation in the Low Density Lipoprotein (LDL) cholesterol levels and
      a decrease in High Density Lipoprotein (HDL) cholesterol levels in the
      individuals who were on protease inhibitors. It was also observed that the HDL
      cholesterol levels decreased with an increase in the duration of the therapy. The
      LDL cholesterol levels increased with the duration of the therapy. CONCLUSION:
      The human immunodeficiency virus infection is itself related to the metabolic
      complications which are aggravated on the use of second line anti retroviral
      therapy. Therefore, after initiating the treatment with protease inhibitors, a
      periodic evaluation of the serum lipid levels and the blood sugar profile should
      be done as a standard care.

PMID- 23542169
TI  - RUNX3 inhibits hypoxia-inducible factor-1alpha protein stability by interacting
      with prolyl hydroxylases in gastric cancer cells.
AB  - RUNX3 is silenced by histone modification and hypoxia-inducible factor (HIF)
      1alpha is stabilized under hypoxia, but little is known of cross-talk between
      RUNX3 and HIF-1alpha under hypoxia. In the present study, the authors
      investigated the effect of RUNX3 on HIF-1alpha stability in gastric cancer cells.
      RUNX3 overexpression was found to downregulate HIF-1alpha stability under
      normoxic and hypoxic conditions. Furthermore, the activity of a luciferase
      reporter containing five copies of vascular endothelial growth factor (VEGF)
      promoter hypoxia-responsive element (5 * HRE) and the amount of secreted VEGF,
      were diminished in RUNX3-expressing but increased in RUNX3-knockdown cells. When
      expression of RUNX3 was recovered using epigenetic reagents the expressions of
      HIF-1alpha and VEGF were clearly suppressed under hypoxic conditions. RUNX3 also
      significantly attenuated the half-life of HIF-1alpha protein, and induced the
      cytosolic localization and ubiquitination of HIF-1alpha. In addition, RUNX3
      directly interacted with the C-terminal activation domain of HIF-1alpha and
      prolyl hydroxylase (PHD) 2 and enhanced the interaction between HIF-1alpha and
      PHD2, which potentiated proline hydroxylation and promoted the degradation of HIF
      1alpha. Furthermore, RUNX3 overexpression significantly inhibited hypoxia-induced
      angiogenesis in vitro and in vivo. Taken together, these results suggest that
      RUNX3 destabilizes HIF-1alpha protein by promoting the proline hydroxylation of
      HIF-1alpha through binding to HIF-1alpha/PHD2. RUNX3 appears to be a novel
      suppressor of HIF-1alpha and of hypoxia-mediated angiogenesis in gastric cancer
      cells. 

PMID- 23542170
TI  - P63 regulates tubular formation via epithelial-to-mesenchymal transition.
AB  - P63, a p53 family member, is expressed as TA and DeltaN isoforms. Interestingly,
      both TAp63 and DeltaNp63 are transcription factors, and regulate both common and
      distinct sets of target genes. p63 is required for survival of some epithelial
      cell lineages, and lack of p63 leads to loss of epidermis and other epithelia in
      humans and mice. Here, we explored the role of p63 isoforms in cell
      proliferation, migration and tubulogenesis by using Madin-Darby Canine Kidney
      (MDCK) tubular epithelial cells in two- or three-dimensional (2-D or 3-D)
      culture. We found that like downregulation of p53, downregulation of p63 and
      TAp63 decreases expression of growth-suppressing genes, including p21, PUMA and
      MIC-1, and consequently promotes cell proliferation and migration in 2-D culture.
      However, in 3-D culture, downregulation of p63, especially TAp63, but not p53,
      decapacitates MDCK cells to form a cyst structure through enhanced epithelial-to
      mesenchymal transition (EMT). In contrast, downregulation of DeltaNp63 inhibits
      MDCK cell proliferation and migration in 2-D culture, and delays but does not
      block MDCK cell cyst formation and tubulogenesis in 3-D culture. Consistent with
      this, downregulation of DeltaNp63 markedly upregulates growth-suppressing genes,
      including p21, PUMA and MIC-1. Taken together, these data suggest that TAp63 is
      the major isoform required for tubulogenesis by maintaining an appropriate level
      of EMT, whereas DeltaNp63 fine-tunes the rate of cyst formation and tubulogenesis
      by maintaining an appropriate expression level of genes involved in cell cycle
      arrest and apoptosis. 

PMID- 23542171
TI  - CTSL2 is a pro-apoptotic target of E2F1 and a modulator of histone deacetylase
      inhibitor and DNA damage-induced apoptosis.
AB  - Aberrant regulation of the pRB/E2F1 pathway has been invariably linked to
      inappropriate proliferation and/apoptosis in human cancers. Therefore,
      understanding the intricacies of the signaling pathway and identification of
      novel E2F1 targets involved in apoptosis could pave way for new therapeutic
      manipulation. Here, we identified CTSL2 (cathepsin L2/cathepsin V) as a novel
      E2F1 target that participates in E2F1-dependent apoptosis. We showed that E2F1
      directly binds to CTSL2 promoter and that CTSL2 is regulated by both exogenous
      and endogenous E2F1. RNAi-mediated depletion of CTSL2 effectively abrogated
      ectopic E2F1-induced apoptosis, coupled with reduced lysosomal membrane
      permeabilization (LMP) and mitochondrial membrane depolarization. CTSL2 knockdown
      also inhibited apoptosis mediated by the endogenous E2F1 activated by DNA damage.
      Furthermore, we showed that CTSL2 depletion in cancer cells resulted in
      inhibition of histone deacetylase inhibitor (HDACi)-induced apoptosis, and
      conversely ectopic overexpression of CTSL2-sensitized cancer cells to HDACi. This
      study uncovered a novel E2F1 target implicated in LMP and apoptosis activation,
      as well as in the modulation of HDACi and chemotherapeutic drugs response. 

PMID- 23542172
TI  - The Ron receptor tyrosine kinase activates c-Abl to promote cell proliferation
      through tyrosine phosphorylation of PCNA in breast cancer.
AB  - Multiple growth pathways lead to enhanced proliferation in malignant cells.
      However, how the core machinery of DNA replication is regulated by growth
      signaling remains largely unclear. The sliding clamp proliferating cell nuclear
      antigen (PCNA) is an indispensable component of the DNA machinery responsible for
      replicating the genome and maintaining genomic integrity. We previously reported
      that epidermal growth factor receptor (EGFR) triggered tyrosine 211 (Y211)
      phosphorylation of PCNA, which in turn stabilized PCNA on chromatin to promote
      cell proliferation. Here we show that the phosphorylation can also be catalyzed
      by the non-receptor tyrosine kinase c-Abl. We further demonstrate that, in the
      absence of EGFR, signaling to PCNA can be attained through the activation of the
      Ron receptor tyrosine kinase and the downstream non-receptor tyrosine kinase c
      Abl. We show that Ron and c-Abl form a complex, and that activation of Ron by its
      ligand, hepatocyte growth factor-like protein (HGFL), stimulates c-Abl kinase
      activity, which in turn directly phosphorylates PCNA at Y211 and leads to an
      increased level of chromatin-associated PCNA. Correspondingly, HGFL-induced Ron
      activation resulted in Y211 phosphorylation of PCNA while silencing of c-Abl
      blocked this effect. We show that c-Abl and Y211 phosphorylation of PCNA is an
      important axis downstream of Ron, which is required for cell proliferation.
      Treatment with a specific peptide that inhibits Y211 phosphorylation of PCNA or
      with the c-Abl pharmacological inhibitor imatinib suppressed HGFL-induced cell
      proliferation. Our findings identify the pathway of Ron-c-Abl-PCNA as a mechanism
      of oncogene-induced cell proliferation, with potentially important implications
      for development of combination therapy of breast cancer. 

PMID- 23542174
TI  - Elevated snoRNA biogenesis is essential in breast cancer.
AB  - Hyperactive ribosomal biogenesis is widely observed in cancer, which has been
      partly attributed to the increased rDNA transcription by Pol I in cancer.
      However, whether small nucleolar RNAs (snoRNAs), a class of non-coding RNAs
      crucial in ribosomal RNA (rRNA) maturation and functionality, are involved in
      cancer remains elusive. We report that snoRNAs and fibrillarin (FBL, an enzymatic
      small nucleolar ribonucleoprotein, snoRNP) are frequently overexpressed in both
      murine and human breast cancer as well as in prostate cancers, and significantly,
      that this overexpression is essential for tumorigenicity in vitro and in vivo. We
      demonstrate that when the elevated snoRNA pathway is suppressed, the tumor
      suppressor p53 can act as a sentinel of snoRNP perturbation, the activation of
      which mediates the growth inhibitory effect. On the other hand, high level of FBL
      interferes with the activation of p53 by stress. We further show that p53
      activation by FBL knockdown is not only regulated by the ribosomal protein-MDM2
      mediated protein stabilization pathway, but also by enhanced PTB-dependent, cap
      independent translation. Together, our data uncover an essential role of
      deregulated snoRNA biogenesis in tumors and a new mechanism of nucleolar
      modulation of p53. 

PMID- 23542173
TI  - Signaling cross-talk in the resistance to HER family receptor targeted therapy.
AB  - Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) have an important
      role in the initiation and progression of various types of cancer. Inhibitors
      targeting these receptor tyrosine kinases are some of the most successful
      targeted anticancer drugs widely used for cancer treatment; however, cancer cells
      have mechanisms of intrinsic and acquired drug resistance that pose as major
      obstacles in drug efficacy. Extensive studies from both clinical and laboratory
      research have identified several molecular mechanisms underlying resistance.
      Among them is the role of signaling cross-talk between the EGFR/HER2 and other
      signaling pathways. In this review, we focus particularly on this signaling cross
      talk at the receptor, mediator and effector levels, and further discuss
      alternative approaches to overcome resistance. In addition to well-recognized
      signaling cross-talk involved in the resistance, we also introduce the cross-talk
      between EGFR/HER2-mediated pathways and pathways triggered by other types of
      receptors, including those of the Notch, Wnt and TNFR/IKK/NF-kappaB pathways, and
      discuss the potential role of targeting this cross-talk to sensitize cells to
      EGFR/HER2 inhibitors. 

PMID- 23542175
TI  - p120 catenin is a key effector of a Ras-PKCE oncogenic signaling axis.
AB  - Within the family of protein kinase C (PKC) molecules, the novel isoform PRKCE
      (PKCE) acts as a bona fide oncogene in in vitro and in vivo models of
      tumorigenesis. Previous studies have reported expression of PKCE in breast,
      prostate and lung tumors above that of normal adjacent tissue. Data from the
      cancer genome atlas suggest increased copy number of PRKCE in triple negative
      breast cancer (TNBC). We find that overexpression of PKCE in a non-tumorigenic
      breast epithelial cell line is sufficient to overcome contact inhibition and
      results in the formation of cellular foci. Correspondingly, inhibition of PKCE in
      a TNBC cell model results in growth defects in two-dimensional (2D) and three
      dimensional (3D) culture conditions and orthotopic xenografts. Using stable
      isotope labeling of amino acids in a cell culture phosphoproteomic approach, we
      find that CTNND1/p120ctn phosphorylation at serine 268 (P-S268) occurs in a
      strictly PKCE-dependent manner, and that loss of PKCE signaling in TNBC cells
      leads to reversal of mesenchymal morphology and signaling. In a model of Ras
      activation, inhibition of PKCE is sufficient to block mesenchymal cell
      morphology. Finally, treatment with a PKCE ATP mimetic inhibitor, PF-5263555,
      recapitulates genetic loss of function experiments impairing p120ctn
      phosphorylation as well as compromising TNBC cell growth in vitro and in vivo. We
      demonstrate PKCE as a tractable therapeutic target for TNBC, where p120ctn
      phosphorylation may serve as a readout for monitoring patient response. 

PMID- 23542176
TI  - Pin1 modulates ERalpha levels in breast cancer through inhibition of
      phosphorylation-dependent ubiquitination and degradation.
AB  - Estrogen receptor-alpha (ERalpha) is an important biomarker used to classify and
      direct therapy decisions in breast cancer (BC). Both ERalpha protein and its
      transcript, ESR1, are used to predict response to tamoxifen therapy, yet certain
      tumors have discordant levels of ERalpha protein and ESR1, which is currently
      unexplained. Cellular ERalpha protein levels can be controlled post
      translationally by the ubiquitin-proteasome pathway through a mechanism that
      depends on phosphorylation at residue S118. Phospho-S118 (pS118-ERalpha) is a
      substrate for the peptidyl prolyl isomerase, Pin1, which mediates cis-trans
      isomerization of the pS118-P119 bond to enhance ERalpha transcriptional function.
      Here, we demonstrate that Pin1 can increase ERalpha protein without affecting
      ESR1 transcript levels by inhibiting proteasome-dependent receptor degradation.
      Pin1 disrupts ERalpha ubiquitination by interfering with receptor interactions
      with the E3 ligase, E6AP, which also is shown to bind pS118-ERalpha. Quantitative
      in situ assessments of ERalpha protein, ESR1, and Pin1 in human tumors from a
      retrospective cohort show that Pin1 levels correlate with ERalpha protein but not
      to ESR1 levels. These data show that ERalpha protein is post-translationally
      regulated by Pin1 in a proportion of breast carcinomas. As Pin1 impacts both
      ERalpha protein levels and transactivation function, these data implicate Pin1 as
      a potential surrogate marker for predicting outcome of ERalpha-positive BC. 

PMID- 23542177
TI  - SIRT1 regulates YAP2-mediated cell proliferation and chemoresistance in
      hepatocellular carcinoma.
AB  - The MST/YAP (mammalian Ste20-like kinase/Yes-associated protein 2) pathway plays
      an important role in hepatocellular carcinoma (HCC). Although post-translational
      modification-especially MST/Lats (large tumor suppressor)-mediated
      phosphorylation and PP1 (protein phosphatase-1)-mediated dephosphorylation-has
      been found to regulate the activity of YAP2, very little is known about its
      acetylation. In our experiments, we observed that the expression of SIRT1 is
      significantly upregulated in the tumor samples of the hepatocarcinoma patients,
      and SIRT1 mRNA level positively correlates with connective tissue growth factor
      (CTGF) mRNA level. We then found that SIRT1 deacetylates YAP2 protein in HCC
      cells and SIRT1-mediated deacetylation increases the YAP2/TEAD4 association,
      leading to YAP2/TEAD4 transcriptional activation and upregulated cell growth in
      HCC cells. Moreover, knockdown of SIRT1 blocks the cisplatin (CDDP)-induced
      nuclear translocation of YAP2 and enhances the chemosensitivity of HCC cells to
      CDDP treatment. Together, our findings reveal a new regulatory mechanism of YAP2
      by the SIRT1-mediated deacetylation that may be involved in HCC tumorigenesis and
      drug resistance. 

PMID- 23542178
TI  - Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary
      resistance to ATP-competitive mTOR inhibitors.
AB  - The mammalian target of rapamycin (mTOR) regulates cell growth by integrating
      nutrient and growth factor signaling and is strongly implicated in cancer. But
      mTOR is not an oncogene, and which tumors will be resistant or sensitive to new
      adenosine triphosphate (ATP) competitive mTOR inhibitors now in clinical trials
      remains unknown. We screened a panel of over 600 human cancer cell lines to
      identify markers of resistance and sensitivity to the mTOR inhibitor PP242. RAS
      and phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutations were
      the most significant genetic markers for resistance and sensitivity to PP242,
      respectively; colon origin was the most significant marker for resistance based
      on tissue type. Among colon cancer cell lines, those with KRAS mutations were
      most resistant to PP242, whereas those without KRAS mutations most sensitive.
      Surprisingly, cell lines with co-mutation of PIK3CA and KRAS had intermediate
      sensitivity. Immunoblot analysis of the signaling targets downstream of mTOR
      revealed that the degree of cellular growth inhibition induced by PP242 was
      correlated with inhibition of phosphorylation of the translational repressor
      eIF4E-binding protein 1 (4E-BP1), but not ribosomal protein S6 (rpS6). In a tumor
      growth inhibition trial of PP242 in patient-derived colon cancer xenografts,
      resistance to PP242-induced inhibition of 4E-BP1 phosphorylation and xenograft
      growth was again observed in KRAS mutant tumors without PIK3CA co-mutation,
      compared with KRAS wild-type controls. We show that, in the absence of PIK3CA co
      mutation, KRAS mutations are associated with resistance to PP242 and that this is
      specifically linked to changes in the level of phosphorylation of 4E-BP1. 

PMID- 23542180
TI  - MR-1 blocks the megakaryocytic differentiation and transition of CML from chronic
      phase to blast crisis through MEK dephosphorylation.
AB  - Chronic myelogenous leukemia (CML) evolves from a chronic phase characterized by
      the Philadelphia chromosome as the sole genetic abnormality and the accumulation
      of mature cells in peripheral blood into blast crisis, which is characterized by
      the rapid expansion of myeloid- or lymphoid-differentiation-arrested blast cells.
      Although ample studies have been conducted on the disease progress mechanisms,
      the underlying molecular mechanisms of the malignant phenotype transition are
      still unclear. In this study, we have shown that myofibrillogenesis regulator-1
      (MR-1) was overexpressed in blast crisis patients and leukemic cells, but there
      was little trace expressed in healthy individuals and in most patients in CML
      chronic phase. MR-1 could inhibit the differentiation of myeloid cells into
      megakaryocytic lineages and accelerate cell proliferation. The molecular
      mechanism responsible for these effects was the interaction of MR-1 with MEK,
      which blocked the MEK/ERK signaling pathway by dephosphorylating MEK. Our results
      provide compelling and important evidence that MR-1 might act as a diagnostic
      marker and potential target of CML progression from chronic phase to blast
      crisis.

PMID- 23542179
TI  - 15-PGDH inhibits hepatocellular carcinoma growth through 15-keto-PGE2/PPARgamma
      mediated activation of p21WAF1/Cip1.
AB  - 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme in prostaglandin
      (PG) metabolism. This study provides important evidence for inhibition of
      hepatocellular carcinoma (HCC) growth by 15-PGDH through the 15-keto
      prostaglandin E2 (15-keto-PGE2)/peroxisome proliferator-activated receptor-gamma
      (PPARgamma)/p21(WAF1/Cip1) signaling pathway. Forced overexpression of 15-PGDH
      inhibited HCC cell growth in vitro, whereas knockdown of 15-PGDH enhanced tumor
      growth parameters. In a tumor xenograft model in severe combined immunodeficiency
      mice, inoculation of human HCC cells (Huh7) with overexpression of 15-PGDH led to
      significant inhibition of tumor growth, whereas knockdown of 15-PGDH enhanced
      tumor growth. In a separate tumor xenograft model in which mouse HCC cells (Hepa1
      6) were inoculated into syngeneic C57BL/6 mice, intratumoral injection of
      adenovirus vector expressing 15-PGDH (pAd-15-PGDH) significantly inhibited
      xenograft tumor growth. The antitumor effect of 15-PGDH is mediated through its
      enzymatic product, 15-keto-PGE2, which serves as an endogenous PPARgamma ligand.
      Activation of PPARgamma by 15-PGDH-derived 15-keto-PGE2 enhanced the association
      of PPARgamma with the p21(WAF1/Cip1) promoter and increased p21 expression and
      association with cyclin-dependent kinase 2 (CDK2), CDK4 and proliferating cell
      nuclear antigen. Depletion of p21 by short hairpin RNA reversed 15-PGDH-induced
      inhibition of HCC cell growth; overexpression of p21 prevented 15-PGDH knockdown
      induced tumor cell growth. These results show a key 15-PGDH/15-keto-PGE2-mediated
      activation of PPARgamma and p21(WAF1/Cip1) signaling cascade that regulates
      hepatocarcinogenesis and tumor progression. 

PMID- 23542181
TI  - Analysis of tyrosine phosphorylation and phosphotyrosine-binding proteins in
      germinating seeds from Scots pine.
AB  - Protein tyrosine phosphorylation in angiosperms has been implicated in various
      physiological processes, including seed development and germination. In conifers,
      the role of tyrosine phosphorylation and the mechanisms of its regulation are yet
      to be investigated. In this study, we examined the profile of protein tyrosine
      phosphorylation in Scots pine seeds at different stages of germination. We
      detected extensive protein tyrosine phosphorylation in extracts from Scots pine
      (Pinus sylvestris L.) dormant seeds. In addition, the pattern of tyrosine
      phosphorylation was found to change significantly during seed germination,
      especially at earlier stages of post-imbibition which coincides with the
      initiation of cell division, and during the period of intensive elongation of
      hypocotyls. To better understand the molecular mechanisms of phosphotyrosine
      signaling, we employed affinity purification and mass spectrometry for the
      identification of pTyr-binding proteins from the extracts of Scots pine
      seedlings. Using this approach, we purified two proteins of 10 and 43 kDa, which
      interacted specifically with pTyr-Sepharose and were identified by mass
      spectrometry as P. sylvestris defensin 1 (PsDef1) and aldose 1-epimerase
      (EC:5.1.3.3), respectively. Additionally, we demonstrated that both endogenous
      and recombinant PsDef1 specifically interact with pTyr-Sepharose, but not Tyr
      beads. As the affinity purification approach did not reveal the presence of
      proteins with known pTyr binding domains (SH2, PTB and C2), we suggest that
      plants may have evolved a different mode of pTyr recognition, which yet remains
      to be uncovered. 

PMID- 23542182
TI  - A synthetic tuber-specific and cold-induced promoter is applicable in controlling
      potato cold-induced sweetening.
AB  - Cold-induced sweetening (CIS) in potato seriously hinders the potato processing
      industry. It could be of great value for genetic improvement of potato CIS to
      have a target gene specifically expressed in cold stored tubers. In this study,
      we used a synthetic promoter, pCL, in potato transformation to drive an antisense
      expression of StvacINV1, the acid vacuolar invertase gene from Solanum tuberosum.
      The measurements of expression and enzyme activity of target gene showed that pCL
      promoter could efficiently govern target gene to express specifically and
      remarkably regulate the activity of acid vacuolar invertase in potato tubers at
      low temperature, furthermore, it had almost no effect in other tissues or the
      tubers under room temperature. The transgenic tubers showed decrease in reducing
      sugar content during storage at low temperature and acceptable chip color without
      significant changes observed in plant morphology and tuberization between the
      nontransgenic and transgenic lines. This tuber-specific and cold-induced feature
      could maximally reduce the background expression of the target gene which might
      bring about potential negative or detrimental effects to plant development. The
      synthetic promoter confirmed here would be optimal for gene function research in
      potato tubers in response to low temperature. 

PMID- 23542184
TI  - Structural and functional alterations induced by two sulfonamide antibiotics on
      barley plants.
AB  - Synthetic veterinary medicines are introduced routinely in the environment after
      animal treatment to prevent and control infectious diseases and up to 80% the
      administered dose can be excreted unaltered. As a consequence, the soil is the
      environment most contaminated by such molecules. However, information about their
      implications on the growth of vegetal organisms is still scarce. With the aim of
      better elucidating the effects of veterinary antibiotics on plants, barley was
      grown in a nutrient solution containing 40 MUM (about 11,500 MUg L(-1)) of two
      well-known sulfonamide antibiotics, sulfadimethoxine (SDM) and sulfamethazine
      (SZ). After 15 d of treatment, the effects on root apparatus were particularly
      evident, while the photosynthetic tissues remained almost unaffected. SDM and SZ
      stimulated root hairs and lateral root development a few mm behind the root tips.
      In particular, from a structural point of view, treated plants showed root
      shortening and an advanced differentiation in comparison to controls, later
      confirmed using light microscopy. At a functional level, the two active molecules
      were found to induce root electrolyte release, such as K(+), possibly due to an
      impairment of membrane permeability. The research concludes that sulfonamides can
      have profound effects on morphology and functionality of roots of crop plants. As
      these alterations might have consequences on their productivity, further studies
      are necessary to assess effects on plants at laboratory and field conditions. 

PMID- 23542183
TI  - Metabolic indicators of drought stress tolerance in wheat: glutamine synthetase
      isoenzymes and Rubisco.
AB  - Drought stress has a considerable impact on the ecosystem and agriculture.
      Continuous water deficit induces early leaf senescence in plants. During this
      process, chloroplasts are degraded and photosynthesis drastically drops. The
      objective of this investigation was to look into the regulation of nitrogen and
      carbon metabolism during water deficit. Rubisco (ribulose-1,5-bisphosphate
      carboxylase/oxygenase; EC 4.1.1.39) and the total protein contents inform us of
      the sink-source relation in plants. Glutamine synthetase (GS, EC 6.3.1.2)
      isoenzymes are good markers of plastid status (GS2) and the nitrogen metabolism
      (GS1). Tolerant and sensitive wheat (Triticum aestivum L.) genotypes were tested,
      which are widely used in agriculture. The amount of protein, Rubisco and GS
      isoforms in leaves were measured during the grain filling period, as indicative
      traits that ultimately determine the onset and stage of senescence. The symptoms
      of senescence first appeared on the oldest and finally on the youngest leaves.
      Drought stress disrupted the sequentiality of senescence in the sensitive
      varieties. An untimely senescence appeared in flag leaves, earlier than in the
      older leaves. Total protein and Rubisco contents decreased and the GS2 isoenzyme
      declined considerably in the youngest leaves. In the tolerant varieties, however,
      these physiological parameters did not change under drought, only the sequential
      senescence of leaf levels accelerated in some cases compared to the control, well
      watered plants. Our results revealed that GS is a good indicator of drought
      stress, which can be applied for the characterization of wheat cultivars in terms
      of drought stress tolerance. 

PMID- 23542185
TI  - Molecular cloning, polyclonal antibody preparation, and characterization of a
      functional iron-related transcription factor IRO2 from Malus xiaojinensis.
AB  - Transcription factors play important roles in plant growth and responses to
      environmental stresses. In this study, a novel basic helix-loop-helix iron
      related transcription factor, IRO2, containing a 762-bp open reading frame and
      encoding 253 amino acids, was cloned from the iron-efficient genotype of Malus
      xiaojinensis. Localization analyses in onion showed that the MxIRO2 protein was
      targeted to the nucleus and activation studies in yeast indicated MxIRO2-BD had
      weak transcriptional activation activity. Prokaryotic expression of MxIRO2 in
      Escherichia coli BL21 (DE3) pLysS cells resulted in high expression levels of the
      protein when induced with isopropyl-beta-d-thiogalactoside. The fusion protein
      was purified using Ni-NTA His-bind resin, and the purified MxIRO2-His fusion
      protein was used as the antigen to immunize a New Zealand rabbit. The resulting
      antiserum was purified by precipitation with 50% saturated ammonium sulfate and
      DEAE Sephadex A-50 chromatography to obtain the immunoglobulin G fraction. The
      expression of MxIRO2 in roots and leaves of M. xiaojinensis seedlings under iron
      deficiency was determined. The results indicated that MxIRO2 was induced in both
      roots and leaves under iron deficiency. In these experimental conditions, the
      transcription and translation levels first increased and then decreased under
      iron deficiency. This work offers an important basis for further investigating
      the mechanisms of fruit tree adaptation to iron deficiency. 

PMID- 23542186
TI  - Optimizing movement.

PMID- 23542187
TI  - Motor proficiency, strength, endurance, and physical activity among middle school
      children who are healthy, overweight, and obese.
AB  - PURPOSE: To compare motor proficiency, strength, endurance, and physical activity
      among children from minority backgrounds who were healthy weight (HW), overweight
      (OW), or obese (OB). METHODS: Eighty-six children, aged 10 to 15 years, of mostly
      Hispanic ethnicity, participated. Children were categorized according to body
      mass index-for-age percentile. Bruininks-Oseretsky Test of Motor Proficiency
      (BOT2) Short Form, Sit-to-Stand (STS), Timed Up and Down Stairs, and 6-Minute
      Walk Test (6MWT) were administered. Physical activity was measured by using
      activity monitors. RESULTS: Forty-five percent of children were classified as
      OW/OB. Children who were OB had lower mean BOT2, STS, and 6MWT performance than
      children of HW. Among children who were OW/OB, daily mean steps were lower and
      sedentary minutes higher than children of HW. In children who were OW/OB, body
      mass index was negatively correlated with BOT2, STS, and abdominal curls.
      CONCLUSION: Children who are OB demonstrate greater impairments in motor
      proficiency, strength, and endurance and participate in less physical activity
      than peers of HW.

PMID- 23542191
TI  - Evaluation of static and dynamic postural balance in children with juvenile
      idiopathic arthritis.
AB  - PURPOSE: To evaluate balance in children with lower limb involvement due to
      juvenile idiopathic arthritis (JIA). METHODS: Twenty-five children with JIA
      manifesting lower extremity arthritis within the previous year and 36 children
      who were healthy (aged 8-18 years) were assessed by using the Biodex Balance
      System (BBS) (Biodex, Shirley, New York). Single-leg static balance (BBS level
      12) and bilateral static and dynamic balance (BBS levels 2 and 7) were measured.
      Lower extremity strength, disease activity, function, and pain were also
      assessed. RESULTS: : Ten subjects with JIA (40%) could not complete single-leg
      balance testing, while all controls did (P < .0001). Bilateral dynamic balance
      was impaired only at BBS level 2 (most unstable). Lower extremity weakness
      correlated with poor balance. CONCLUSION: A significant proportion of children
      with leg arthritis have impaired balance. Proprioceptive exercises may emerge as
      an important therapy in the treatment of lower extremity arthritis.

PMID- 23542189
TI  - Reliability and validity of the TIMPSI for infants with spinal muscular atrophy
      type I.
AB  - PURPOSE: This study examined the reliability and validity of the Test of Infant
      Motor Performance Screening Items (TIMPSI) in infants with type I spinal muscular
      atrophy (SMA). METHODS: After training, 12 evaluators scored 4 videos of infants
      with type I SMA to assess interrater reliability. Intrarater and test-retest
      reliability was further assessed for 9 evaluators during a SMA type I clinical
      trial, with 9 evaluators testing a total of 38 infants twice. Relatedness of the
      TIMPSI score to ability to reach and ventilatory support was also examined.
      RESULTS: Excellent interrater video score reliability was noted (intraclass
      correlation coefficient, 0.97-0.98). Intrarater reliability was excellent
      (intraclass correlation coefficient, 0.91-0.98) and test-retest reliability
      ranged from r = 0.82 to r = 0.95. The TIMPSI score was related to the ability to
      reach (P <= .05). CONCLUSION: The TIMPSI can reliably be used to assess motor
      function in infants with type I SMA. In addition, the TIMPSI scores are related
      to the ability to reach, an important functional skill in children with type I
      SMA.

PMID- 23542193
TI  - Development of items that assess physical function in children who use
      wheelchairs.
AB  - PURPOSE: To assess the content, format, and comprehension of the Patient Reported
      Outcomes Measurement Information System (PROMIS) pediatric physical function
      related to mobility items for children who use wheelchairs (WCs). METHODS: During
      a cognitive interview, 14 children, aged 8 to 12 years, who use WCs, verbalized
      their thoughts when answering PROMIS items. The questionnaire appraisal system
      was used to code summarized text from the interviews. RESULTS: The children
      requested items be more specific and include options for reporting adaptive ways
      of performing and participating. How they would answer the item depended on the
      situation and specific environmental supports and constraints they may have
      experienced. CONCLUSIONS: As rehabilitation professionals develop and use self
      reported outcome measures, they should explore what is important to children who
      use WCs regarding their views on physical functioning, the influences of the
      environment, and variability in the use of devices to assist with functional
      mobility.

PMID- 23542195
TI  - GMFM in infancy: age-specific limitations and adaptations.
AB  - PURPOSE: To evaluate longitudinal applicability of the gross motor function
      measure (GMFM) in infants younger than 2 years. METHODS: Twelve infants at very
      high risk for cerebral palsy were enrolled between 1 and 9 months corrected age.
      The children were assessed 4 times during 1 year with the GMFM-66, GMFM-88, and
      other neuromotor tests. RESULTS: Longitudinal use of the GMFM in infancy was
      hampered by age and function-specific limitations. The GMFM-66 differentiated
      less at lower-ability levels than at higher-ability levels. The GMFM-88
      demonstrated flattening of the developmental curve when infants had developed
      more motor abilities. We formulated adaptations for the longitudinal use of GMFM
      in infancy. CONCLUSIONS: To facilitate use of the GMFM in infancy, an adapted
      version may be an option. Further research is required to assess reliability and
      validity, and in particular, the sensitivity to change of the suggested
      adaptations.

PMID- 23542197
TI  - Cardiorespiratory response during physical therapist intervention for infants and
      young children with chronic respiratory insufficiency.
AB  - PURPOSE: To document physical therapist intervention activities and
      cardiorespiratory response for young children with chronic respiratory
      insufficiency. METHODS: Twelve children born prematurely, 6 to 30 months
      chronological age and admitted to inpatient pulmonary rehabilitation for oxygen
      and/or ventilation weaning, were included. During 3 intervention sessions, a
      second physical therapist recorded intervention activity and heart rate (HR),
      oxygen saturation (SaO2), and respiratory rate. Total time and median HR, SaO2,
      and respiratory rate for each activity were calculated. An analysis of variance
      was used to compare HR and SaO2 across activity based on intersession
      reliability. RESULTS: Sitting activities were most frequent and prone least
      frequent. Median cardiorespiratory measures were within reference standards for
      age. No adverse effects were seen during intervention and no significant
      difference was found in HR and SaO2 among intervention activities. CONCLUSION:
      Young children with chronic respiratory insufficiency are able to tolerate
      intervention with close monitoring by the physical therapist.

PMID- 23542199
TI  - Treadmill training following orthopedic surgery in lower limbs of children with
      cerebral palsy.
AB  - PURPOSE: To determine the effect of treadmill training on gross motor function
      and functional mobility in children with cerebral palsy (CP) receiving physical
      therapy following orthopedic surgery for the lower limbs. METHODS: Children with
      CP between 8 and 15 years of age participated and were divided into 2 groups:
      those having undergone soft tissue surgery and those having undergone both soft
      tissue and bone surgery. The program consisted of 12 weeks of treadmill training
      without partial weight support at a frequency of one 30-minute session per week.
      RESULTS: Significant improvements were found on the gross motor function measure
      88 after treadmill training; distance traveled on the 6 meter walk test; and time
      tolerated on the treadmill. CONCLUSIONS: Treadmill training during physical
      therapy is beneficial for children with CP who undergo orthopedic surgery in the
      lower limbs.

PMID- 23542201
TI  - Intervention in the first weeks of life for infants born late preterm: a case
      series.
AB  - Infants born late preterm (34-36 weeks of gestation) account for 350 000 US
      births per year, are at risk for developmental delays, and are rarely included in
      intervention studies. PURPOSE: To describe a novel parent-delivered movement
      intervention program for very young infants and outcomes following intervention
      and to evaluate the feasibility of using a comprehensive set of outcome measures.
      SUMMARY OF KEY POINTS: Two infants born late preterm received intervention from
      0.5 to 2.0 months of adjusted age. Development, postural control, reaching, and
      object exploration assessments were completed at 3 time points. The intervention
      was well tolerated by the family. Improvements in developmental outcomes,
      postural control, and object exploration are presented. STATEMENT OF CONCLUSION:
      Very early movement experience provided daily by parents may improve development.
      In combination, norm-referenced and behavioral measures appear sensitive to
      changes in infant behaviors.

PMID- 23542202
TI  - Application of the NICU practice guidelines to treat an infant in a level III
      NICU.
AB  - PURPOSE: The purpose of this case report was to determine how current physical
      therapy (PT) practice in the neonatal intensive care unit (NICU), with 1 infant,
      adhered to the neonatal PT decision-making framework that was developed as part
      of the NICU practice guidelines for clinical care. SUMMARY OF KEY POINTS: Most PT
      interventions implemented in this NICU were supported by the algorithm, with some
      steps more readily implemented than others. CONCLUSIONS: This case report
      highlights the utility of the NICU clinical decision-making algorithm for not
      only assisting with developing an evidence-based PT plan of care for an infant at
      high risk but also its usefulness in revealing NICU programmatic and policy
      strengths and areas for improvement. RECOMMENDATIONS FOR CLINICAL PRACTICE: The
      NICU developmental and therapeutic teams are encouraged to conduct similar
      endeavors to assess the quality of PT care in their NICUs.

PMID- 23542203
TI  - Strength training for a child with suspected developmental coordination disorder.
AB  - BACKGROUND: Children with developmental coordination disorder (DCD) demonstrate
      difficulty with feedforward motor control and use varied compensatory strategies.
      PURPOSE: To examine gross motor function changes following strength training in a
      child with motor control difficulties. CASE DESCRIPTION: A girl aged 6 years 11
      months, with apraxia and hypotonia, and demonstrating motor delays consistent
      with DCD. INTERVENTION: Twenty-four strength training sessions were completed
      using a universal exercise unit. OUTCOMES: Postintervention scores significantly
      improved on the Bruininks-Oseretsky test of motor proficiency, second edition,
      and the Canadian occupational performance measure scores and raised the
      developmental coordination disorder questionnaire, revised 2007, scores above the
      range where DCD is suspected. Nonsignificant changes in strength were observed.
      DISCUSSION: Improved function and significant gains in manual coordination were
      observed following blocked practice of isolated, simple joint movements during
      strength training. Improved motor skills may be because of effective use of
      feedforward control and improved stabilization. Strength training does not
      rehearse skills using momentum, explaining nonsignificant changes in locomotor or
      locomotion areas.

PMID- 23542204
TI  - Healthy Active Living in Youth With Neuromotor Disability (HALYNeD) Project: a
      translational project with researchers, pediatric physical therapists, and
      patients working together toward evidence-based exercise prescription.

PMID- 23542205
TI  - Phylogenetic analysis of Deladenus nematodes parasitizing northeastern North
      American Sirex species.
AB  - The parasitic nematode Deladenus siricidicola is a biological control agent of
      the invasive woodwasp, Sirex noctilio. Since the discovery of S. noctilio in pine
      forests of northeastern North America in 2005, a biological control program
      involving the Kamona strain of D. siricidicola has been under consideration.
      However, North American pine forests have indigenous Sirex spp. and likely harbor
      a unique assemblage of associated nematodes. We assessed phylogenetic
      relationships among native Deladenus spp. in the northeastern United States and
      the Kamona strain of D. siricidicola. We sequenced three genes (mtCO1, LSU, and
      ITS) from nematodes extracted from parasitized Sirex spp. collected inside and
      outside of the range of S. noctilio. Our analyses suggest cospeciation between
      four North American Sirex spp. and their associated nematode parasites. Within
      two S. noctilio individuals we found nematodes that we hypothesize are normally
      associated with Sirex nigricornis. One individual of the native S. nigricornis
      contained Deladenus normally associated with S. noctilio. We discuss nematode
      host fidelity in this system and the potential for non-target impacts of a
      biological control program using D. siricidicola against S. noctilio.

PMID- 23542206
TI  - Contrasting patterns of transposable element and satellite distribution on sex
      chromosomes (XY1Y2) in the dioecious plant Rumex acetosa.
AB  - Rumex acetosa is a dioecious plant with the XY1Y2 sex chromosome system. Both Y
      chromosomes are heterochromatic and are thought to be degenerated. We performed
      low-pass 454 sequencing and similarity-based clustering of male and female
      genomic 454 reads to identify and characterize major groups of R. acetosa
      repetitive DNA. We found that Copia and Gypsy retrotransposons dominated,
      followed by DNA transposons and nonlong terminal repeat retrotransposons. CRM and
      Tat/Ogre retrotransposons dominated the Gypsy superfamily, whereas
      Maximus/Sireviruses were most abundant among Copia retrotransposons. Only one
      Gypsy subfamily had accumulated on Y1 and Y2 chromosomes, whereas many
      retrotransposons were ubiquitous on autosomes and the X chromosome, but absent on
      Y1 and Y2 chromosomes, and others were depleted from the X chromosome. One group
      of CRM Gypsy was specifically localized to centromeres. We also found that
      majority of previously described satellites (RAYSI, RAYSII, RAYSIII, and RAE180)
      are accumulated on the Y chromosomes where we identified Y chromosome-specific
      variant of RAE180. We discovered two novel satellites-RA160 satellite dominating
      on the X chromosome and RA690 localized mostly on the Y1 chromosome. The
      expression pattern obtained from Illumina RNA sequencing showed that the
      expression of transposable elements is similar in leaves of both sexes and that
      satellites are also expressed. Contrasting patterns of transposable elements
      (TEs) and satellite localization on sex chromosomes in R. acetosa, where not only
      accumulation but also depletion of repetitive DNA was observed, suggest that a
      plethora of evolutionary processes can shape sex chromosomes.

PMID- 23542208
TI  - The secretome in cancer progression.
AB  - The secretome is the collection of all macromolecules secreted by a cell, and is
      a vital aspect of cell-cell communication in eukaryotes. In cancer, tumour cells
      often display secretomes with altered composition compared to the normal tissue
      from which they are derived. These changes can contribute to the acquisition and
      maintenance of the recognised hallmarks of cancer. In addition, evidence is
      emerging for a more sophisticated role for the tumour secretome in cancer, with
      significant implications for malignant disease progression. In this review, we
      highlight recent advances in our understanding of factors contributing to
      secretome alterations in cancer, including genetic mutations, microRNA-based
      regulation and the influence of the tumour microenvironment. The contribution of
      secreted factors in maintenance and function of cancer stem cells, and of tumour
      derived factors in specification of a pre-metastatic niche are also discussed.
      Collectively, evidence from the current literature suggests that the tumour
      secretome, consisting of factors derived from cancer stem cells, non-stem cells
      and the surrounding stroma, plays a deterministic role in cancer progression, and
      may constitute a key therapeutic target in many cancers. This article is part of
      a Special Issue entitled: An Updated Secretome. 

PMID- 23542207
TI  - An ABC method for estimating the rate and distribution of effects of beneficial
      mutations.
AB  - Determining the distribution of adaptive mutations available to natural selection
      is a difficult task. These are rare events and most of them are lost by chance.
      Some theoretical works propose that the distribution of newly arising beneficial
      mutations should be close to exponential. Empirical data are scarce and do not
      always support an exponential distribution. Analysis of the dynamics of
      adaptation in asexual populations of microorganisms has revealed that these can
      be summarized by two effective parameters, the effective mutation rate, Ue, and
      the effective selection coefficient of a beneficial mutation, Se. Here, we show
      that these effective parameters will not always reflect the rate and mean effect
      of beneficial mutations, especially when the distribution of arising mutations
      has high variance, and the mutation rate is high. We propose a method to estimate
      the distribution of arising beneficial mutations, which is motivated by a common
      experimental setup. The method, which we call One Biallelic Marker Approximate
      Bayesian Computation, makes use of experimental data consisting of periodic
      measures of neutral marker frequencies and mean population fitness. Using
      simulations, we find that this method allows the discrimination of the shape of
      the distribution of arising mutations and that it provides reasonable estimates
      of their rates and mean effects in ranges of the parameter space that may be of
      biological relevance.

PMID- 23542209
TI  - Oxidative stress mediates apoptotic effects of ascorbate and dehydroascorbate in
      human Myelodysplasia cells in vitro.
AB  - The Myelodysplastic Syndromes are stem cell heterogeneous disorders characterized
      by peripheral cytopenias and hypercellular bone marrow, which can evolute to
      acute leukaemia. Vitamin C can act as an antioxidant, ascorbic acid (AA) donates
      two electrons and becomes oxidized to dehydroascorbic acid (DHA). Under
      physiological conditions, vitamin C predominantly exists in its reduced (AA) form
      but also exists in trace quantities in the oxidized form (DHA). This study
      evaluates the therapeutic potential of vitamin C in Myelodysplastic Syndromes
      (MDSs). F36P cells (MDS cell line) were treated with ascorbate and
      dehydroascorbate alone and in combination with cytarabine. Cell proliferation and
      viability were assessed by trypan blue assay and cell death was evaluated by
      optical microscopy and flow cytometry. The role of reactive oxygen species,
      mitochondrial membrane potential, BAX, BCL-2 and cytochrome C were also assessed.
      Vitamin C decreases cell proliferation and viability in a concentration, time and
      administration dependent-manner inducing cell death by apoptosis, which was shown
      to be associated to an increased in superoxide production, mitochondrial membrane
      depolarization. These compounds modulate BCL-2, BAX and cytochrome C release.
      These results suggest that vitamin C induces cell death trough apoptosis in F36P
      cells and may be a new therapeutic approach in Myelodysplasia.

PMID- 23542210
TI  - Induction of G2/M arrest, caspase activation and apoptosis by alpha-santonin
      derivatives in HL-60 cells.
AB  - Sesquiterpene lactones (SLs) are natural products with a variety of biological
      activities. Previously, we demonstrated the cytotoxic effects of three new alpha
      santonin derivatives on different tumor cell lines with low toxic effects upon
      peripheral human leukocytes. Here, we evaluated the mechanism of action triggered
      by these derivatives. HL-60 cell cycle determined after 24h treatment revealed a
      significant inhibition on cell-cycle progression and leading to an increasing of
      cells in G2/M [7.6% and 9.0% for compound 3% and 9.0% and 8.6% for compound 4 (1
      and 2 MUM, respectively)]. However, after 48 h exposure, all compounds caused
      G2/M reduction and a significant DNA fragmentation. Compounds 2, 3 and 4 were
      able to induce apoptosis on leukemia cells, which was corroborated by
      phosphatidyserine externalization and activation of caspases-3 and -7 after 24h
      exposure. None of the derivatives analyzed caused depolarization of mitochondrial
      membrane within 24h of incubation, suggesting the involvement of the extrinsic
      apoptotic pathway in the death process. The antiproliferative action of these
      compounds is related to the DNA synthesis inhibition and cell cycle arrest, which
      probably lead to apoptosis activation. Therefore, these santonin derivatives are
      promising lead candidates for development of new cytotoxic agents.

PMID- 23542211
TI  - Improving the sustainability of granular iron/pumice systems for water treatment.
AB  - Metallic iron (Fe(0)) is currently used in subsurface and above-ground water
      filtration systems on a pragmatic basis. Recent theoretical studies have
      indicated that, to be sustainable, such systems should not contain more than 60%
      Fe(0) (vol/vol). The prediction was already validated in a Fe(0)/sand system
      using methylene blue as an operational tracer. The present work is the first
      attempt to experimentally verify the new concept using pumice particles. A well
      characterized pumice sample is used as operational supporting material and is
      mixed with 200 g of a granular Fe(0), in volumetric proportions, varying from 0
      to 100%. The resulting column systems are characterized (i) by the time dependent
      evolution of their hydraulic conductivity and (ii) for their efficiency for the
      removal of Cu(II), Ni(II), and Zn(II) from a three-contaminants-solution (about
      0.3 mM of each metal). Test results showed a clear sustainability of the long
      term hydraulic conductivity with decreasing Fe(0)/pumice ratio. In fact, the pure
      Fe(0) system clogged after 17 days, while the 25% Fe(0) system could operate for
      36 days. The experimental data confirmed the view that well-designed Fe(0) PRBs
      may be successful at removing both reducible and non-reducible metal species.

PMID- 23542212
TI  - Management of groundwater resources in relation to oasis sustainability: the case
      of the Nefzawa region in Tunisia.
AB  - In Southern Tunisia Nefzawa region, the deep fossil aquifers have been used
      intensively to support agricultural activities and economic development. This
      resulted in the degradation of groundwater resources as well as in their
      conflicting uses. Efficient management strategies that allow for compromises
      between economic development and water resource preservation are needed. Such
      strategies require initial understanding of the interactions between stakeholders
      and water related processes. This paper aims to conceptualize the causalities
      between the management of deep fossil aquifers and the functioning of oasian
      agrosystems. By merging biophysical and socioeconomic issues, we propose an
      integrated assessment of public policies devoted to the management of groundwater
      resources. The failure of public policies emphasizes both the lack of
      consideration for individual initiatives and the long-term uncertainties on such
      policies, where farmer practices have been driven by economic and cultural
      factors. A set of indicators is next proposed for assessing the preservation of
      deep fossil aquifers that support agricultural and economic development. Further
      methodological improvements are needed to evaluate the long-term effects of
      constraints and incentives on the management of deep fossil aquifers.

PMID- 23542213
TI  - Use of municipal solid waste compost as a growth media for an energy plant
      (rapeseed).
AB  - Objective of this work was to study the effect of mixtures of municipal solid
      waste (MSW) compost with a peat based growth media on the yields of rapeseed. The
      MSW compost and the peat were respectively mixed at ratios equal to 10%:90%,
      20%:80% and 50%:50% (wet weight basis). A randomized block design was adopted
      with 5 treatments and 3 blocks per treatment. The 50%:50% mixture achieved a
      statistically higher yield (dry weight and average leaf area) compared to all
      other treatments, whilst compost alone led to the lowest shoot growth. Negative
      correlations were calculated between the total contents of Pb, Ni and Cd of the
      plant tissues and the corresponding dry weights of the shoots. Regression
      equations were developed that described shoot yields as a function of the water
      holding capacity, pH, electrical conductivity, C/N ratio and the total and
      leachable contents of certain metals in the growth media.

PMID- 23542214
TI  - Modeling shrub encroachment in subalpine grasslands under different environmental
      and management scenarios.
AB  - Woody plants are spreading in many alpine and subalpine ecosystems and are
      expected to continue increasing in response to land abandonment and global
      warming. This encroachment threatens species diversity, and considerable efforts
      have been deployed to control it. In this study, we combined a lattice model and
      field data to investigate the efficiency of different management strategies in
      controlling shrub encroachment in alpine grasslands. The model parameter values
      were estimated in the field based on the thorny shrub Echinospartum horridum
      (erizon) which is currently encroaching in central Spanish Pyrenees. Our study
      shows that encroachment could accelerate if climate warming continues. Different
      management scenarios consisting of a gradient of livestock pressures, fire events
      and mechanical removal were simulated to identify scenarios able to control the
      expansion of shrubs into grasslands. Our study shows that grazing alone cannot
      stop encroachment. Rather, a combination of grazing and shrub removal (either by
      fire or mechanical removal) is needed, and our model can help estimate the
      frequency and intensities of the shrub removal. This model can be used to
      investigate the consequences of different management scenarios and environmental
      variability which could be of practical value in the preservation of alpine
      grasslands.

PMID- 23542215
TI  - External costs of atmospheric lead emissions from a waste-to-energy plant: a
      follow-up assessment of indirect exposure via topsoil ingestion.
AB  - In this study the Impact Pathway Approach (IPA) was used to calculate the
      external costs associated with indirect exposure, via topsoil ingestion, to
      atmospheric emissions of lead (Pb) from a waste-to-energy plant in Denmark. Three
      metal-specific models were combined to quantify the atmospheric dispersion of
      lead, its deposition and accumulation in topsoil, and the increase in blood lead
      concentration for children resulting from lead intake via topsoil ingestion. The
      neurotoxic impact of lead on children was estimated using a lead-specific
      concentration-response function that measures impaired cognitive development in
      terms of IQ points lost per each incremental MUg/dl of lead in blood. Since IQ
      loss during childhood can be associated with a percent decrease in expected
      lifetime earnings, the monetary value of such an impact can be quantified and the
      external costs per kg of lead emitted from the plant were then calculated. The
      costs of indirect exposure calculated over a time horizon of 100 years, for the
      sub-population of children of 0-3 years, and discounted at 3%, were in the range
      of 15-30 ?/kg. Despite the continued accumulation of lead in topsoil resulting in
      increasing future indirect exposure, the results indicate that costs associated
      with this exposure pathway are of the same order of magnitude as costs associated
      with direct exposure via inhalation, calculated at 45-91 ?/kg. Moreover, when the
      monetary value of future impacts is discounted to the present, the differences
      between the two exposure pathways are diminished. Finally, setting a short time
      horizon reduces the uncertainties but excludes part of the costs of indirect
      exposure from the assessment.

PMID- 23542216
TI  - Application of response surface methodology (RSM) for optimisation of COD, NH3-N
      and 2,4-DCP removal from recycled paper wastewater in a pilot-scale granular
      activated carbon sequencing batch biofilm reactor (GAC-SBBR).
AB  - In this study, the potential of a pilot-scale granular activated carbon
      sequencing batch biofilm reactor (GAC-SBBR) for removing chemical oxygen demand
      (COD), ammoniacal nitrogen (NH3-N) and 2,4-dichlorophenol (2,4-DCP) from recycled
      paper wastewater was assessed. For this purpose, the response surface methodology
      (RSM) was employed, using a central composite face-centred design (CCFD), to
      optimise three of the most important operating variables, i.e., hydraulic
      retention time (HRT), aeration rate (AR) and influent feed concentration (IFC),
      in the pilot-scale GAC-SBBR process for recycled paper wastewater treatment.
      Quadratic models were developed for the response variables, i.e., COD, NH3-N and
      2,4-DCP removal, based on the high value (>0.9) of the coefficient of
      determination (R(2)) obtained from the analysis of variance (ANOVA). The optimal
      conditions were established at 750 mg COD/L IFC, 3.2 m(3)/min AR and 1 day HRT,
      corresponding to predicted COD, NH3-N and 2,4-DCP removal percentages of 94.8,
      100 and 80.9%, respectively.

PMID- 23542217
TI  - Human neurocysticercosis: immunological features involved in the host's
      susceptibility to become infected and to develop disease.
AB  - Human neurocysticercosis (NC) is a clinically and radiologically heterogeneous
      disease caused by the establishment of Taenia solium larvae in the central
      nervous system. Herein, the immunological and endocrinological features involved
      in resistance to infection and severe forms of the disease are reviewed, and
      their clinical relevance is discussed.

PMID- 23542218
TI  - The EXCITE Trial: reacquiring upper-extremity task performance with early versus
      late delivery of constraint therapy.
AB  - OBJECTIVE: This study examines performance of Wolf Motor Function Test (WMFT)
      tasks in terms of the ability of EXCITE trial participants (who had suffered a
      stroke 3-9 months before recruitment) to complete the task within the timed
      interval. METHODS: Data were collected from participants who received constraint
      induced movement therapy (CIMT) 3 to 9 months poststroke (CIMT-I, n = 106) or 15
      to 21 months poststroke (CIMT-D, n = 116). Performance on the 15 timed WMFT tasks
      was converted into binary values, and changes in completion of the tasks were
      analyzed with generalized estimating equation methods, under the assumption of a
      binomial or Poisson process for completion. RESULTS: During CIMT, the CIMT-I
      group showed significant within-group improvements in 3 fine-movement tasks and
      in total noncompleted tasks (noncompletes), whereas the CIMT-D group did not (P
      <= .0036). CIMT-I improvement was significantly greater than CIMT-D improvement
      for the lifting pencil task and total noncompletes. During the year following
      CIMT, neither group showed significant changes in completion of WMFT tasks. Over
      all time intervals, only the CIMT-I group displayed significant improvement in
      several tasks and total noncompletes. Between groups, there were significant and
      almost-significant differences between the improvements of the 2 groups in 3
      tasks requiring fine distal movement. CONCLUSION: Receiving CIMT earlier appears
      to improve reacquisition and retention of WMFT tasks, especially those requiring
      fine motor skills. Combined with earlier findings, these results indicate that
      improvements in existing motor abilities are possible with both immediate and
      delayed CIMT, but early CIMT is necessary for significant reacquisition of tasks.

PMID- 23542219
TI  - Population codes in the visual cortex.
AB  - Every sensory event elicits activity in a broad population of cells that is
      distributed within and across cortical areas. How these neurons function together
      to represent the sensory environment is a major question in systems neuroscience.
      A number of proposals have been made, and recent advances in multi-neuronal
      recording have begun to allow researchers to test the predictions of these
      population-coding theories. In this review, I provide an introduction to some of
      the key concepts in population coding and describe several studies in the recent
      literature. The focus of this review is on sensory representation in the visual
      cortex and related perceptual decisions. The frameworks used to study population
      coding include population vectors, linear decoders, and Bayesian inference.
      Simple examples are provided to illustrate these concepts. Testing theories of
      population coding is an emerging subject in systems neuroscience, but advances in
      multi-neuronal recording and analysis suggest that an understanding is within
      reach.

PMID- 23542220
TI  - Molecular mechanism for trimetric G protein-coupled thermosensation and synaptic
      regulation in the temperature response circuit of Caenorhabditis elegans.
AB  - How the nervous system controls the sensation and memory of information from the
      environment is an essential question. The nematode Caenorhabditis elegans is a
      useful model for elucidating neural information processing that mediates
      sensation and memory. The entire nervous system of C. elegans consists of only
      302 neurons, and their wiring diagram has been revealed by electron microscopy
      analysis. Here, we review the molecular and physiological mechanisms responsible
      for the neural circuit-mediated temperature-seeking behavior (thermotaxis) in C.
      elegans. Recent molecular biology studies and optogenetic analyses, such as the
      optical manipulation of neural activity, and neural imaging have revealed the
      novel concept of neural calculation. Most significantly, trimetric G
      proteincoupled thermosensation, single sensory neuron-based memory, and the
      orchestrated synaptic transmission system have been elucidated.

PMID- 23542221
TI  - Neurophysiological insights into the pathophysiology of REM sleep behavior
      disorders: a review.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a clinical condition
      characterized by an intermittent or complete loss of muscle atonia and an
      increase of phasic muscular activity during REM sleep (or Stage R), leading to
      complex nocturnal motor behaviors. Correct and early diagnosis is important
      because RBD may lead to serious injuries and is a well-treatable disorder. Since
      the characteristic electrophysiologic finding in patients with RBD is the
      increased electromyographic tone during REM sleep/Stage R, simultaneous
      video/polysomnography recording is essential for diagnosing this parasomnia.
      Moreover, several neurophysiological techniques have been used to improve our
      knowledge and understanding of this troubling sleep disorder. We reviewed the
      most important studies employing quantitative electroencephalography, event
      related potentials, transcranial magnetic stimulation, brainstem reflexes and
      cortico-muscular coherence analysis. All these neurophysiological techniques have
      proven to provide a valuable tool to gain insight into the pathophysiological
      mechanisms underlying RBD. The review concludes with a brief discussion on the
      possible future implications for improving therapeutic approaches.

PMID- 23542222
TI  - Clinical effect of individualized parenteral nutrition vs conventional method in
      patients undergoing autologous hematopoietic SCT.
AB  - Malnutrition in patients undergoing hematopoietic SCT is known as a risk factor
      for adverse effects and is directly or indirectly responsible for excess
      mortality and morbidity. We designed the present study to evaluate the effects of
      individualized parenteral nutrition (PN) and compare the present method to the
      conventional PN. Individualized PN based on the Harris-Benedict equation was
      administered to 30 patients after hematopoietic SCT and was compared with an age,
      gender and disease matched group of patients who underwent hematopoietic SCT with
      conventional PN. These two groups were compared on clinical, hematological,
      nutritional outcomes. Comparing duration of hospital stay (P value<0.0001),
      infection (P value = 0.01), time to platelet engraftment (P value = 0.02), units
      of packed cell transfusion (P value = 0.006) and decrease in body weight (P value
      = 0.004) showed significant differences between the two groups. In conclusion,
      the use of individualized PN seems more beneficial than conventional PN.

PMID- 23542223
TI  - Allogeneic hematopoietic cell transplantation for consolidation of VGPR or CR for
      newly diagnosed multiple myeloma.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative
      approach in patients with multiple myeloma, but its use for consolidation of
      first remission has not yet been fully explored. Twenty-two myeloma patients with
      very good partial response (VGPR) or CR received allogeneic peripheral blood
      grafts as consolidation from HLA-matched donors between 2007 and 2012.
      Conditioning regimens were fludarabine (30 mg/m(2) i.v. if with bortezomib and 40
      mg/m(2) i.v. when without bortezomib, * 4 days) plus melphalan (70 mg/m(2)
      intravenously * 2 days) with (n=13) or without (n=9) bortezomib (1.3 mg/m(2)).
      The cumulative incidence of grades II - IV acute GVHD at day 100 was 45% (95% CI:
      24-65%) and moderate-to-severe chronic GVHD at 2 years was 46% (95% CI: 19-69%).
      With a median follow-up of 18 (range, 2-61) months, the 2-year PFS estimate is
      74.8% (95% CI: 45-90%), which compares favorably with the 52% (95% CI: 35-66%)
      after autologous HCT for similar patients (a median follow-up of 30 (range, 9-55)
      months). We are conducting a phase 2 study to assess the efficacy of allogeneic
      HCT as post-remission therapy. 

PMID- 23542224
TI  - A variant in IRF3 impacts on the clinical outcome of AML patients submitted to
      Allo-SCT.
AB  - Allo-SCT has a strong curative potential for AML patients mainly due to a GVL
      effect. Unfortunately, GvL and GVHD are intimately linked. IFN regulatory factor
      3 (IRF3), by modulating innate immune reactions, could impact on the incidence
      and intensity of GVL and GVHD. We analyzed two gene variants in IRF3 (rs7251 and
      rs2304205) on the clinical outcome of 249 AML patients submitted to HLA-identical
      sibling allo-SCT. Patients with a donor carrying the dominant GG gene variant in
      rs7251 had, as compared with GC and CC variants, a lower acute GVHD (aGVHD) III
      IV incidence (4% vs 11% vs 27%; P=0.0078), a higher relapse incidence (49% vs 35%
      vs 26%; P=0.018), and lower TRM (7% vs 24% vs 18%; P=0.0065). In functional
      studies, the GG variant was associated with lower production of IFN-gamma,
      decreased lymphocyte proliferation after antigen presentation by DCs, and lower
      cytotoxic response of mature natural killer cells. Patients carrying the AA
      dominant variant in rs2304205 had higher relapse incidence (50% vs 39% vs 18%,
      P=0.0068). The presence of both variants (GG in rs7251 and AA in rs2304205) in
      donors and patients resulted in a stronger clinical impact. 

PMID- 23542225
TI  - Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis
      congenita-related BM failure.
AB  - BM failure (BMF) is a major and frequent complication of dyskeratosis congenita
      (DKC). Allogeneic hematopoietic SCT (allo-HSCT) represents the only curative
      treatment for BMF associated with this condition. Transplant-related
      morbidity/mortality is common especially after myeloablative conditioning
      regimens. Herein, we report nine cases of patients with DKC who received an allo
      SCT at five different member centers within the Eastern Mediterranean Blood and
      Marrow Transplantation Registry. Between October 1992 and February 2011, nine DKC
      patients (male, 7 and female, 2), with a median age at transplantation of 19.1
      (4.9-31.1) years, underwent an allo-HSCT from HLA-matched, morphologically normal
      related donors (100%). Preparative regimens varied according to different
      centers, but was reduced intensity conditioning (RIC) in eight patients. Graft
      source was unstimulated BM in five cases (56%) and G-CSF-mobilized PBSCs in four
      (44%) cases. The median stem cell dose was 6.79 (2.06-12.4) * 10(6) cells/kg body
      weight. GVHD prophylaxis consisted of CsA in all nine cases; MTX or mycophenolate
      mofetil were added in five (56%) and two (22%) cases, respectively. Anti
      thymocyte globulin was administered at various doses and scheduled in four (44%)
      cases. Median time-to-neutrophil engraftment was 21 (17-27) days. In one case,
      late graft failure was noted at 10.4 months post allo-HSCT. Only one patient
      developed grade II acute GVHD (11%). Extensive chronic GVHD was reported in one
      case, whereas limited chronic GVHD occurred in another four cases. At a median
      follow-up of 61 (0.8-212) months, seven (78%) patients were still alive and
      transfusion independent. One patient died of metastatic gastric adenocarcinoma
      and graft failure was the cause of death in another patient. This study suggests
      that RIC preparative regimens are successful in inducing hematopoietic cell
      engraftment in patients with BMF from DKC. Owing to the limited sample size, the
      use of registry data and heterogeneity of preparative as well as GVHD prophylaxis
      regimens reported in this series, we are unable to recommend a particular regimen
      to be considered as the standard for patients with this disease. 

PMID- 23542226
TI  - Effects of soil type and genotype on lead concentration in rootstalk vegetables
      and the selection of cultivars for food safety.
AB  - Lead (Pb) contamination of soil poses severe health risks to humans through
      vegetable consumption. The variations of Pb concentration in different parts of
      rootstalk vegetables (radish, carrot and potato) were investigated by using
      twelve cultivars grown in acidic Ferralsols and neutral Cambisols under two Pb
      treatments (125 mg kg(-1) and 250 mg kg(-1) for Ferralsols; 150 mg kg(-1) and 300
      mg kg(-1) for Cambisols) in a pot experiment. The Pb concentration in edible
      parts was higher in Ferralsols under two Pb treatments, with range from 0.28 to
      4.14, 0.42-10.66 mg kg(-1) (fresh weight) respectively, and all of them exceeded
      the food safety standard (0.1 mg kg(-1)) recommended by the Codex Alimentarius
      Commission of FAO and WHO. The Pb concentration in edible parts was significantly
      affected by genotype, soil type and the interaction between these two factors.
      The variation of Pb concentration in different cultivars was partially governed
      by Pb absorption and the transfer of Pb from aerial to edible part. The results
      revealed that caution should be paid to the cultivation of rootstalk vegetables
      in Pb-contaminated Ferralsols without any agronomic management to reduce Pb
      availability and plant uptake. For Cambisols with slight to moderate Pb
      contamination, growing potato cultivar Shandong No.1 and Chongqing No.1 was
      effective in reducing the risk of Pb entering human food chain. The results
      suggest the possibility of developing cultivar- and soil-specific planting and
      monitoring guidelines for the cultivation of rootstalk vegetables on slight to
      moderate Pb-contaminated soils.

PMID- 23542227
TI  - Nutrient pollution in shallow aquifers underlying pit latrines and domestic solid
      waste dumps in urban slums.
AB  - The lack of proper on-site sanitation in unsewered low-income areas is becoming
      an important source of nutrient-rich wastewater leaching to groundwater and can
      potentially lead to eutrophication. For typical conditions in sub-Saharan Africa,
      the nutrient loading of nitrogen (N) and phosphorus (P) from on-site sanitation
      systems to aquifers is largely unknown. In this study, we assessed the dissolved
      nutrient loads (nitrate (NO3), ammonium (NH4) and orthophosphate (o-PO4)) and the
      processes likely affecting them in aquifers underlying two on-site sanitation
      systems in an unsewered low-income urban slum in Kampala, Uganda; a domestic
      solid waste dump and a site with two pit latrines. The impact of the two types of
      sites was assessed by comparing the upgradient and downgradient nutrient
      concentrations and loads along groundwater flow lines. Significant pollution to
      groundwater originated from the pit latrine site with downgradient nutrient loads
      increasing by factors of 1.7 for NO3, 10.5 for NH4 and 49 for o-PO4. No effect of
      leaching of nutrients to groundwater was found from the waste dump. We estimated
      that approximately 2-20% of total N and less than 1% of total P mass input was
      lost to groundwater from the pit latrines. The bulk of N leached to groundwater
      was in the form of NH4. Mn-reducing conditions prevailed in the shallow aquifer
      which suggested that nitrification was the main process affecting NH4
      concentrations. Phosphorus was likely retained in the soils by precipitating as
      MnHPO4 and Ca5(PO4)3(OH). Our results indicated that pit latrines in alluvial
      aquifer systems can be highly effective for the removal of nutrients depending on
      hydrological, hydrochemical and geochemical conditions in the aquifer receiving
      wastewater. Improvements to make the current pit latrine systems better for
      nutrient containment are suggested based on findings from this study.

PMID- 23542228
TI  - Zeolitized tuffs in pedotechnique for the reclamation of abandoned quarries. A
      case study in the Campania region (Italy).
AB  - The present study aims to assess the evolution of different proto-horizons as
      embryonic soils built by pedotechnologies for the reclamation and management of
      derelict and damaged lands, such as abandoned quarries. The model proto-horizons
      were assembled by utilizing coarse limestone gravel or zeolitized Phlegraean
      Yellow Tuff (PYT) as mineral components and commercial compost-amendments or a
      phosphorite-poultry manure mixture as organic matrices for growth of a pasture
      grass under controlled conditions. The evolution of the model proto-horizons was
      followed by an evaluation of the stability and modification of the organic matter
      (OM) with reference to plant development. The results suggest that the natural
      carbonatic substrate occurring in limestone quarries was unable to sustain
      significant plant growth, while the PYT was suitable and efficient as a pedogenic
      substrate because it supported plant growth and induced a conspicuous
      accumulation of OM due to root activity. In particular, OM, including humic and
      non-humic components, greatly increased in the PYT treatment with the phosphorite
      poultry manure mixture showing a concurrent trend toward humification.
      Conversely, an overall tendency toward degradation of OM was detected in the PYT
      model proto-horizon treated with commercial compost. Feasibility estimates show
      that quarry restoration costs appear reasonable where environmental impacts are
      high.

PMID- 23542229
TI  - Assessing the stability of phosphorus in lake sediments amended with water
      treatment residuals.
AB  - The reuse of drinking water treatment residuals (WTRs) to immobilize phosphorus
      (P) in sediments is a novel application for lake restoration. The recycling of
      WTRs is beneficial from both environmental and economic standpoints. This work
      assessed the stability of P in sediments found in Lake Taihu and Lake Baiyangdian
      before and after being amended with WTRs. The results indicated that WTRs had
      similar effects on the stability of P in each of the lake's sediments. WTRs can
      significantly reduce the P desorption potential of the sediments at pH values
      less than 11. WTRs can also inhibit the competitive adsorption of SiO4(2-) with
      P. Compared with the raw sediments, the organic matter in the sediments, ion
      strength and anaerobic conditions presented minor undesirable effects on the
      stability of P in the WTRs-amended sediments. Moreover, WTRs can increase the P
      adsorption rate and capacity of the sediments. Overall, these results
      demonstrated that WTRs can make P more stable in lake sediments under various
      conditions.

PMID- 23542230
TI  - Systematic review of the effects of maternal hypertension in pregnancy and
      antihypertensive therapies on child neurocognitive development.
AB  - As many as 15% of women experience hypertension during pregnancy. Large
      proportions of them are receiving antihypertensive medications. This review
      investigated whether hypertension itself, or the antihypertensive medications,
      adversely affect long term child neurocognitive development. The existing
      evidence suggests that methyldopa and labetalol probably do not adversely affect
      neurobehavioral development. Although an increasing body of evidence suggests
      adverse neurocognitive effects of the hypertension itself, none of the existing
      studies examined simultaneously the effects of both hypertension and the drugs
      used therapeutically. The confounding effects by indication must be addressed in
      future studies.

PMID- 23542231
TI  - Anthropogenic radionuclides in the atmosphere observed at Tsukuba:
      characteristics of the radionuclides derived from Fukushima.
AB  - During a serious accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP),
      a huge quantity of radionuclides was released into the atmosphere and ocean. We
      measured anthropogenic radionuclides in surface air at Tsukuba, about 170 km from
      the FDNPP. On March 15, 2011, we detected the radioactivity released from the
      Fukushima accident in air samples at Tsukuba. The major radionuclides that we
      observed were radioiodine ((131)I, (132)I, (133)I) and radiocesium ((134)Cs,
      (136)Cs, (137)Cs). This radioiodine consisted of gaseous and particulate forms;
      the percentage of particulate (131)I in the total (131)I ranged from 0 to 86%.
      The percentage of the particulate (131)I to the total (131)I increased on the
      arrival of the plumes from major emissions of the FDNPP. After activities of the
      radionuclides attained the maximum on March 15, 2011, the FDNPP-derived
      radionuclides decreased rapidly in surface air. The activity median aerodynamic
      diameter of (131)I-bearing particles was 0.7 MUm, while those of (134)Cs- and
      (137)Cs-bearing particles were larger than 1 MUm. Large variations of ratios of
      (131)I/(137)Cs, (132)Te/(137)Cs, and (99)Mo ((99m)Tc)/(137)Cs (all involving
      different elements) suggest that the behaviors of these radionuclides in the
      atmosphere, including the processes of their emission, differed each other.

PMID- 23542232
TI  - Cell-based therapies for ocular inflammation.
AB  - Since the plasticity and the potential for re-programming cells has become widely
      accepted, there has been great interest in cell-based therapies. These are being
      applied to a range of diseases, not least ocular diseases, where it is assumed
      that there is a reduced risk of immune rejection although this may be more
      perceived than real. There are two broad classes of cell-based therapies: those
      aimed at restoring structure and function of specific tissues and cells; and
      those directed towards restoring immunological homeostasis by controlling the
      damaging effects of inflammatory disease. Stem cells of all types represent the
      first group and prototypically have been used with the aim of regenerating
      failing cells. In contrast, immune cells have been suggested as potential
      modulators of inflammation. However, there is functional overlap in these two
      applications, with some types of stem cells, such as mesenchymal stem cells,
      demonstrating a potent immunomodulatory effect. This review summarises recent
      information on cell based therapies for ocular disease, with special emphasis on
      ocular inflammatory disease, and explores current uses, potential and
      limitations.

PMID- 23542233
TI  - Recent advances on the development of wound dressings for diabetic foot ulcer
      treatment--a review.
AB  - Diabetic foot ulcers (DFUs) are a chronic, non-healing complication of diabetes
      that lead to high hospital costs and, in extreme cases, to amputation. Diabetic
      neuropathy, peripheral vascular disease, abnormal cellular and cytokine/chemokine
      activity are among the main factors that hinder diabetic wound repair. DFUs
      represent a current and important challenge in the development of novel and
      efficient wound dressings. In general, an ideal wound dressing should provide a
      moist wound environment, offer protection from secondary infections, remove wound
      exudate and promote tissue regeneration. However, no existing dressing fulfills
      all the requirements associated with DFU treatment and the choice of the correct
      dressing depends on the wound type and stage, injury extension, patient condition
      and the tissues involved. Currently, there are different types of commercially
      available wound dressings that can be used for DFU treatment which differ on
      their application modes, materials, shape and on the methods employed for
      production. Dressing materials can include natural, modified and synthetic
      polymers, as well as their mixtures or combinations, processed in the form of
      films, foams, hydrocolloids and hydrogels. Moreover, wound dressings may be
      employed as medicated systems, through the delivery of healing enhancers and
      therapeutic substances (drugs, growth factors, peptides, stem cells and/or other
      bioactive substances). This work reviews the state of the art and the most recent
      advances in the development of wound dressings for DFU treatment. Special
      emphasis is given to systems employing new polymeric biomaterials, and to the
      latest and innovative therapeutic strategies and delivery approaches.

PMID- 23542234
TI  - Gelatin coating to stabilize the transfection ability of nucleic acid polyplexes.
AB  - Amphiphilic polymers are effective in complexing and delivering therapeutic
      nucleic acids, such as plasmid DNA (pDNA) and short interfering RNA (siRNA).
      However, long-term stability of the complexes is not desirable, as it may have an
      impact on the transfection efficiency in vivo. To develop a method to preserve
      complex stability we first showed that pDNA complexes formed with the amphiphilic
      polymer linoleic acid-substituted polyethylenimine (PEI-LA) and incubated at 37
      degrees C lost ~90% of their transfection efficiency after only 24h of complex
      formation. Polyethyleneglycol modification of complexes to control the increase
      in complex size and incubation in scaffolds used for implantation did not
      preserve the transfection ability of the complexes. Among a variety of approaches
      explored, gelatin coating of complexes was found to be the best at maintaining
      the original transfection efficiency. Mechanistic studies suggested that improved
      complex uptake, not size stability, was responsible for retention of the
      transfection efficiency. Similarly to the results with pDNA, gelatin coating also
      prevented the decreases in uptake and silencing efficiency of siRNA complexes
      observed following incubation at 37 degrees C. Gelatin-stabilized complexes were,
      furthermore, effective in vivo and led to subcutaneous transgene expression with
      a low pDNA dose that was otherwise ineffective. We conclude that a simple gelatin
      coating approach offers an efficient means to preserve the transfection
      efficiency of polyplexes.

PMID- 23542235
TI  - Comparative study of human aortic and mitral valve interstitial cell gene
      expression and cellular function.
AB  - Valve interstitial cells (VICs) are essential for valvular pathogenesis. However,
      the transcriptional profiles and cellular functions of human aortic VICs (hAVICs)
      and mitral VICs (hMVICs) have not been directly compared. We performed NimbleGen
      gene expression profiling analyses of hAVICs and hMVICs. Seventy-eight known
      genes were differentially expressed between hAVICs and hMVICs. Higher expression
      of NKX2-5, TBX15, OGN, OMD, and CDKN1C and lower expression of TBX5, MMP1, and
      PCDH10 were found in hAVICs compared to hMVICs. The differences in these genes,
      excepting OGN and OMD, remained in rheumatic VICs. We also compared cell
      proliferation, migration, and response to mineralization medium. hMVICs
      proliferated more quickly but showed more calcium deposition and alkaline
      phosphatase activity than hAVICs after culture in mineralization medium,
      indicating that hMVICs were more susceptible to in vitro calcification. Our
      findings reveal differences in the transcription profiles and cellular functions
      of hAVICs and hMVICs.

PMID- 23542236
TI  - The association of taxane resistance genes with the clinical course of ovarian
      carcinoma.
AB  - Taxane and platinum-based chemotherapy regimens are standard treatment for
      advanced ovarian carcinoma. Expression levels of putative markers of taxane
      resistance in carcinoma tissues and paired peritoneal samples (n=55) and in 16
      samples of ovaries without signs of carcinoma were compared with clinical data
      and the patients' time to progression. KIF14, PRC1, CIT and ABCC1 genes were
      significantly overexpressed in carcinomas when compared with normal ovarian
      tissues, while ABCB1 and CASP9 expression was decreased. Associations of protein
      expression of the proliferation marker Ki-67 with KIF14, PRC1, ABCB1 and CASP2
      were found. Lastly, it was discovered that ABCB1 and CASP2 levels associated with
      FIGO stage and that the CIT level associated with the time to progression of
      ovarian carcinoma patients (P<0.0001). In conclusion, ABCB1, CASP2, KIF14, PRC1
      and CIT genes seem to associate with surrogate markers of ovarian carcinoma
      progression and CIT gene associates with therapy outcome. 

PMID- 23542237
TI  - Automated, reproducible, titania-based phosphopeptide enrichment strategy for
      label-free quantitative phosphoproteomics.
AB  - An automated phosphopeptide enrichment strategy is described using titanium
      dioxide (TiO2)-packed, fused silica capillaries for use with liquid
      chromatography (LC)-mass spectrometry (MS)/MS-based, label-free proteomics
      workflows. To correlate an optimum peptide:TiO2 loading ratio between different
      particle types, the ratio of phenyl phosphate-binding capacities was used. The
      optimum loading for the column was then verified through replicate enrichments of
      a range of quantities of digested rat brain tissue cell lysate. Fractions were
      taken during sample loading, multiple wash steps, and the elution steps and
      analyzed by LC-MS/MS to gauge the efficiency and reproducibility of the
      enrichment. Greater than 96% of the total phosphopeptides were detected in the
      elution fractions, indicating efficient trapping of the phosphopeptides on the
      first pass of enrichment. The quantitative reproducibility of the automated setup
      was also improved greatly with phosphopeptide intensities from replicate
      enrichments exhibiting a median coefficient of variation (CV) of 5.8%, and 80% of
      the identified phosphopeptides had CVs below 11.1%, while maintaining >85%
      specificity. By providing this high degree of analytical reproducibility, this
      method allows for label-free phosphoproteomics over large sample sets with
      complex experimental designs (multiple biological conditions, multiple biological
      replicates, multiple time-points, etc.), including large-scale clinical cohorts.

PMID- 23542238
TI  - Occurrence of Trichodinid Ciliophorans (Ciliophora: Peritrichida) in the
      freshwater fishes of the river Churni with description of Trichodina glossogobae
      sp. nov. in West Bengal, India.
AB  - Between January 2011 and March 2011 occurrence of trichodinid ciliophorans were
      studied in the freshwater fishes of the river Churni. The biodiversity survey
      revealed presence of a new species of the genus Trichodina (Ehrenberg 1830)
      infesting Glossogobius giuris (Hamilton-Buchanan). Another freshwater fish Labeo
      bata (Hamilton 1822) were found to be infested with two species of the genus
      Tripartiella Lom 1959: Tripartiella bulbosa (Davis 1947) Lom 1959 and T. copiosa
      Lom 1959. Adhesive disc size of the new Trichodina species is small measuring
      30.6-46.9 (36.2 +/- 3.9) MUm in diameter. The centre of the disc is finely
      granular and transforms into dark when impregnated with silver. The overall
      prevalence of this species is 15.6% (12/77). Tripartiella bulbosa and T. copiosa
      are very small sized ciliophorans, measuring 16.7-23.8 (20.6 +/- 2.2) MUm and
      15.2-22.4 (19.7 +/- 1.9) MUm in diameter, respectively.

PMID- 23542239
TI  - SPIO-PICsome: development of a highly sensitive and stealth-capable MRI nano
      agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles
      (PICsomes).
AB  - Size controllable polyion complex vesicles (PICsomes), composed of biocompatible
      poly(ethylene glycol) (PEG) and poly(amino acid)s, have an extremely prolonged
      lifetime in the bloodstream that enables them to accumulate effectively in tumors
      via the enhanced permeability and retention (EPR) effect. The purpose of this
      study was to use PICsomes to synthesize a highly sensitive MRI contrast agent for
      more precise tumor detection. We synthesized SPIO-Cy5-PICsomes (superparamagnetic
      iron oxide nanoparticle-loaded Cy5-cross-linked Nano-PICsomes) and characterized
      them using dynamic light scattering and transmission electron microscopy in vitro
      and evaluated their ability to detect subcutaneously grafted tumors in vivo with
      MRI. The transverse relaxivity (r2) of the SPIO-Cy5-PICsomes (r2=663+/-28mM(-1)s(
      1)) was 2.54 times higher than that of bare clinically-used SPIO. In in vivo MRI
      experiments on mice subcutaneously grafted with colon-26 tumor cells, the tumor
      signal was significantly altered at 3h after SPIO-Cy5-PICsome administration and
      persisted for at least 24h. Small and early-stage in vivo tumors (3days after
      grafting, approximately 4mm(3)) were also clearly detected with MRI. SPIO-loaded
      PICsomes are sensitive MRI contrast agents that can act as a powerful nanocarrier
      to detect small tumors for early diagnosis.

PMID- 23542240
TI  - Discussion: double venous system drainage in deep inferior epigastric perforator
      flap breast reconstruction: a single-surgeon experience.

PMID- 23542241
TI  - Capsular contracture after breast reconstruction: collagen fiber orientation and
      organization.
AB  - BACKGROUND: Breast implant capsular contracture is a common complication of
      implant-based breast reconstruction. To develop nonsurgical interventions to
      combat breast capsular contractures, a clearer understanding of the process is
      required. Comparing breast implant-related capsular contracture to the fibrotic
      scarring process, the hypothesis is that these processes differ with regard to
      the compaction of collagen fibers within the connective tissue matrix. METHODS:
      Morphologic differences in the connective tissue matrix by light, polarized
      light, and fluorescence microscopy documents these differences. Discarded Baker
      grade II and III periimplant capsules harvested during routine breast
      reconstructive operations were used for the evaluation. RESULTS: Within severe
      breast capsule contractures, light microscopy revealed the absence of mast cells,
      whereas polarized light microcopy showed that collagen fiber bundles were
      consolidated into thick cable-like structures. In less severe breast capsules,
      mast cells were present, whereas thick cable-like collagen structures were
      absent. By fluorescence microscopy, fibroblast populations associated with severe
      contractures were oriented perpendicular to the long axis, suggesting a spiral
      orientation in the compaction of these cable-like structures. These findings were
      absent in less severe contractures. CONCLUSIONS: To the authors' knowledge, these
      histologic findings in breast implant capsules are unreported and unique when
      compared with other fibrotic contractures. Elucidating the biological mechanisms
      involved in the reorganization of collagen fiber bundles that lead to implant
      related capsular contracture is a critical step for developing strategies to
      treat and control breast capsule contractures.

PMID- 23542242
TI  - Repairing the high-riding nipple with reciprocal transposition flaps.
AB  - The high-riding nipple-areola complex is a clinical problem that can be
      encountered following cosmetic and reconstructive breast surgery. Because of the
      desire to avoid scars on the superior aspect of the breast and the limited
      availability of superior breast skin, it can be technically challenging to place
      the nipple-areola complex in a lower position. Multiple surgical strategies have
      attempted to lower it, and each has its advantages and disadvantages. Reciprocal
      rotation flaps have been used by the authors with success. They describe the
      surgical technique and outcomes in five breasts. The medical records of all
      patients who had reciprocal rotation flaps for high-riding nipple-areola
      complexes performed by the senior author (S.L.S.) were reviewed. The
      institutional review board-approved review included preoperative history and
      examination, surgical findings, surgical technique, and postoperative course.
      Five reciprocal rotation flap procedures were performed on four patients between
      2005 and 2012 for high-riding nipple-areola complexes. The high-riding nipple
      areola complexes were all iatrogenic, following reconstruction for nipple-sparing
      mastectomy or mastopexy. All nipple-areola complexes were successfully lowered
      with an average follow-up duration of 2.1 years. One breast that had undergone
      previous radiation therapy had a nipple-areola complex flap that appeared
      ischemic; the patient underwent hyperbaric oxygen therapy and the flap fully
      survived. Reciprocal rotation flaps are an effective strategy for management of
      the high-riding nipple-areola complex and can be safely performed with thoughtful
      planning and careful surgical technique. This technique is riskier in the
      irradiated breast but may be facilitated with hyperbaric oxygen therapy.

PMID- 23542243
TI  - The impact of poly implant prothese fraud on breast cancer patients: a report by
      the institut curie.
AB  - In March of 2010, French authorities suspended the use of breast implants made by
      the company Poly Implant Prothese. Institut Curie is a large cancer center, and
      Poly Implant Prothese was one major silicone-filled breast implant brand used.
      This report describes the impact of the fraudulent implants worldwide and more
      specifically on patient care at the authors' unit. From 2002 to 2009, the median
      number of Poly Implant Prothese implants removed per year was 32. Since the first
      alert in March of 2010, 252 of these breast implants were removed in 2010 and
      2011. The breast implants removed were mainly reported as normal, with a rupture
      rate of less than 5 percent before 2008. However, the annual rupture rate has
      increased from 2008 to 2011 (8, 14, 20, and 23 percent, respectively). The
      Institut Curie, in conjunction with breast cancer patients, has organized a
      management plan to deal with this major industrial fraud. Its surveillance
      program of breast cancer patients facilitated the management of patients during
      this difficult time.

PMID- 23542244
TI  - Skin perfusion and oxygenation changes in radiation fibrosis.
AB  - BACKGROUND: Ionizing radiation is known to have deleterious chronic effects on
      skin, including fibrosis and poor wound healing, hypothesized as mediated by
      ischemia and hypoxia. Past studies have been unable to simultaneously investigate
      changes in perfusion and oxygenation as separate parameters. Hyperspectral
      imaging has emerged as a tool with which to concurrently measure skin perfusion
      and oxygenation. The authors investigated the use of hyperspectral imaging in a
      novel murine model of chronic radiation injury. METHODS: Areas of flank skin (n =
      20) on hairless mice were exposed to a 50-Gy dose of beta-radiation.
      Hyperspectral imaging acquisition was performed at select points through 8 weeks.
      Immunohistochemical staining and gene expression analysis were performed to
      evaluate cutaneous vascular density, epidermal cell hypoxia, and angiogenic
      factors. RESULTS: All irradiated areas developed a chronic-phase wound by day 28.
      Hyperspectral imaging demonstrated a 21 percent decline in perfusion on day 56 (p
      < 0.001), whereas oxygenation levels were unchanged. A 1.7-fold reduction in
      blood vessel density was measured in irradiated skin compared with control tissue
      (p < 0.001), but no difference in epidermal cell hypoxia was observed. Vascular
      endothelial growth factor and related receptor expression were significantly
      lower in irradiated tissue. CONCLUSIONS: The authors' analysis does not support
      the presence of hypoxia in chronic-phase irradiated skin but suggests that
      hypoperfusion may be a predominant characteristic. The concurrent states of
      hypoperfusion and normoxia may be explained by the lower metabolic demands of
      fibrosed tissue.

PMID- 23542245
TI  - Effects of CB-VEGF-A injection in rat flap models for improved survival.
AB  - BACKGROUND: Various carriers have been tested as drug delivery systems in an
      attempt to sustain the action of growth factors. Gene therapy has also been
      adopted to achieve lasting effects but without satisfactory results. Because the
      authors believe that the angiogenic effect of vascular endothelial growth factor
      (VEGF) can be enhanced by anchoring the fusion protein composed of the
      Clostridium-derived collagen-binding domain and recombinant VEGF-A164 (CB-VEGF-A)
      in the tissue, they examined the changes in blood flow of random pattern flaps
      following treatment of the dorsal region of the rat with the fusion proteins
      before skin flap elevation. METHODS: The authors administered CB-VEGF-A
      subcutaneously into the dorsal region of Sprague-Dawley rats 7 days before
      creation of skin flaps, and compared the necrosis rate observed on the seventh
      day after flap elevation with that of vehicle controls. The authors also
      performed comparison with a group treated by subcutaneous administration of non
      collagen-binding domain-binding VEGF. The skin flaps were also examined
      histologically. RESULTS: The flap necrosis rate was lower in the CB-VEGF-A group
      (36.7 +/- 7.4 percent) than in the control group (48.2 +/- 5.4 percent). However,
      no improvement was observed in the non-collagen-binding domain-binding VEGF
      group. Moreover, histologic examination revealed an increase in the subcutaneous
      blood vessel counts. CONCLUSION: CB-VEGF-A has an angiogenic effect on rat dorsal
      skin flaps and improves flap survival.

PMID- 23542246
TI  - Biphasic fusion of the murine posterior frontal suture.
AB  - BACKGROUND: Craniosynostosis is the premature fusion of cranial sutures early in
      development. Mice are commonly used to study the mechanisms driving both normal
      and pathologic cranial suture development. Despite their frequency of use as a
      model, the time course of bone formation and mineralization during fusion of
      mouse posterior frontal suture is not well defined. METHODS: To address this,
      C57Bl/6J mice were euthanized at ages ranging from 6 to 107 days, and the
      posterior frontal sutures were imaged using micro-computed tomography. Scans were
      analyzed with an image-processing algorithm that was previously validated with
      serial histology to quantify both suture fusion and mineral content. The
      expression profile of genes associated with key developmental time points was
      examined using real-time polymerase chain reaction in both the bone and the dura.
      RESULTS: Results demonstrate that the bones of the posterior frontal suture come
      together during days 10 to 20 and then increase in mineral content and volume
      between days 21 and 45. The onset of posterior frontal suture fusion was
      associated with an increase in cartilage-associated genes on day 12. Later
      mineralization of the suture was associated with an increase in mRNAs for
      osteoblast differentiation markers, bone morphogenetic proteins, and bone
      morphogenetic protein inhibitors. CONCLUSIONS: Complete analysis fusion posterior
      frontal suture shows that it occurs in a discontinuous biphasic manner. The first
      phase is from days 10 to 20 and involves production of cartilage. A second
      mineralization phase from days 21 to 45 was seen with both the imaging algorithm
      and changes in gene expression.

PMID- 23542247
TI  - Positive botulinum toxin type a response is a prognosticator for migraine surgery
      success.
AB  - BACKGROUND: The objective of the study was to determine whether botulinum toxin
      type A injections can serve as a prognosticator for migraine surgery success.
      METHODS: Patients who underwent migraine surgery from 2000 to 2010 by the senior
      author (B.G.) were reviewed. Patients were included if they had botulinum toxin
      type A injection before surgery; had completed postinjection, postsurgery
      Migraine Headache Questionnaires; and had at least 1-year follow-up. Outcome
      variables include patient demographics and Migraine Headache Index. Treatment
      success was defined as at least a 50 percent reduction in Migraine Headache
      Index. RESULTS: One hundred eighty-eight patients were included; 144 reported
      successful migraine headache reduction after injection (success group) and 44 did
      not (failure group). The groups were well matched for age, migraine headache
      characteristics, and number of surgical sites (p > 0.05). The surgery success
      rate was significantly higher in the success group overall (90.3 percent versus
      72.3, p = 0.003), and in patients who reported botulinum toxin type A success and
      subsequent same-site surgery (97.9 percent versus 71.4 percent, p < 0.0001).
      Botulinum toxin type A success was prognostic for surgery success at the frontal
      trigger site (trigger site I) (92.5 percent versus 69.2 percent, p = 0.012), the
      temporal trigger site (trigger site II) (95.5 percent versus 73.3 percent, p =
      0.005), and the occipital trigger site (trigger site IV) (95.9 percent versus
      62.5 percent, p = 0.0003). Six patients had exclusively septum or turbinate (site
      III) surgery, and all failed injections. CONCLUSIONS: Positive botulinum toxin
      type A response is a significant predictor of migraine surgery success. When
      injections fail, nonmuscular abnormalities should be considered.

PMID- 23542248
TI  - Ear lobule reconstruction using nasal septal cartilage.
AB  - Surgical reconstruction of an earlobe requires adequate support without
      sacrificing the delicacy necessary for an attractive result. A two-stage ear
      lobule reconstruction using a mastoid skin pocket and cartilage from the nasal
      septum was performed in six patients. The earlobe aesthetics were acceptable and
      allowed ear piercing. There were no major complications, including no loss of
      flap, graft extrusion, septal perforation, or infection. Range of follow-up was 1
      to 6 years, with an average of 3 years. No revisions have been performed. A two
      stage technique for ear lobule reconstruction is described using septal cartilage
      to preserve shape and definition that has the additional advantage of minimal
      morbidity.

PMID- 23542249
TI  - Discussion: resident involvement and plastic surgery outcomes: an analysis of
      10,356 patients from the American College ofSurgeons National Surgical Quality
      Improvement Program Database.

PMID- 23542250
TI  - The level of evidence presented at plastic surgery meetings: what do we have to
      learn?
AB  - BACKGROUND: Internationally, plastic surgery societies have placed an increasing
      emphasis on the importance of evidence-based medicine. The authors aimed to
      categorize levels of evidence of podium presentations at three major North
      American plastic surgical meetings, and to assess the factors associated with a
      higher level evidence. METHODS: Presentations at the 2010/2011 meetings of three
      of the largest societies of plastic surgeons in North America were evaluated for
      the area of research, number and origin of authors, subdomain of plastic surgery,
      number of centers of collaboration, number of subjects, study subtype, and level
      of evidence. RESULTS: One hundred eighty-eight presentations were screened, and
      126 met eligibility criteria. The American Society of Plastic Surgeons was the
      largest meeting with 74 presentations (58.7 percent). Breast (23.8 percent) and
      craniofacial (21.4 percent) topics were most frequently covered. Most studies had
      five or fewer authors (76.4 percent), were conducted at a single center (84.3
      percent), were therapeutic (89.7 percent), and had 50 or fewer subjects (36.8
      percent). Two studies (1.6 percent) were level I, 11 (8.7 percent) were level II,
      54 (42.9 percent) were level III, 46 (36.5 percent) were level IV, and 13 (10.3
      percent) were level V. Overall, the mean level of evidence was 3.45, and one of
      every 10 presentations was of higher level of evidence (level I or II). Higher
      level evidence presentations were found to be associated with multicenter
      studies. CONCLUSIONS: Evidence presented at major plastic surgical meetings is
      rarely level I and infrequently level II. Opportunities to create greater
      awareness of the need for prospective high-level studies are needed.

PMID- 23542252
TI  - Anatomy of the sural nerve: cadaver study and literature review.
AB  - BACKGROUND: The sural nerve is commonly used as donor for nerve grafting.
      Contrary to its constant retromalleolar position, formation and course of the
      proximal sural nerve show great variability. The coexistence of different and
      deceptive terminologies contributes to the complexity, and reviewing the
      international literature is confusing. Because detailed anatomical knowledge is
      essential for efficient and safe sural nerve harvesting, this study aims to bring
      clarity. METHODS: Previous sural nerve reports listed in the PubMed database and
      established anatomical textbooks were reviewed. Different terminologies were
      compared and adjusted. Anatomical details and variations were noted. Subtle
      prospective anatomical dissections and comparison with actual data followed.
      RESULTS: Two hundred twenty-one relevant reports were identified and worked up
      going back to the nineteenth century. Fourteen established German and English
      language anatomical textbooks were reviewed. Thirty lower limbs were dissected.
      In total, this study pools the information of more than 2500 sural nerves.
      CONCLUSIONS: This study covers all information about the sural nerve anatomy
      published internationally. The coexistence of different and confusing
      terminologies is pinpointed and adjusted to allow comparison of previous reports
      and to gain a coordinated data pool of more than 2500 investigated sural nerves.
      Detailed features are clearly described and summarized, findings from the
      authors' own prospective dissections complete these data, and the prior existing
      anatomical confusion is resolved. Finally, clinical implications are described.

PMID- 23542251
TI  - Sharps injuries: the risks and relevance to plastic surgeons.
AB  - Surgeons are at risk for injury in the operating room daily. Because of the
      ubiquity of occupational hazards, injuries remain prevalent and expensive.
      Although occupational hazards can include musculoskeletal conditions,
      psychosocial stress, radiation exposure, and the risk of communicable diseases,
      sharps injuries remain the most common among surgeons in practice and the most
      frequent route of transmission of blood-borne pathogens. Therefore, increased
      attention to the health, economic, personal, and social implications of these
      injuries is essential for appropriate management and future prevention.

PMID- 23542253
TI  - The influence of evidence in the surgical treatment of thumb basilar joint
      arthritis.
AB  - BACKGROUND: For surgical treatment of thumb carpometacarpal joint arthritis,
      current evidence suggests that simple trapeziectomy is as effective as and may be
      safer than trapeziectomy and ligament reconstruction with or without tendon
      interposition. The authors examined whether current practice patterns in the
      surgical treatment of thumb carpometacarpal joint arthritis reflect adoption of
      simple trapeziectomy as best practice, and investigated whether surgeon
      preferences and third-party payer patterns are associated with use of simple
      trapeziectomy. METHODS: The authors performed a retrospective cross-sectional
      study of 6776 surgical treatments for thumb carpometacarpal joint arthritis using
      the all-payer State Ambulatory Surgery Database for Florida, from 2006 to 2009.
      Multinomial regression analysis was applied to examine associations between
      covariates, describing surgeon and third-party payer factors and type of
      procedure performed. An intraclass correlation coefficient was calculated to
      determine how much of the difference in patient outcome (procedure type) is
      attributable to differences between surgeons. RESULTS: Across surgeon
      characteristics included in the analysis, patients' outcome probabilities were
      over 90 percent in favor of treatment with trapeziectomy and ligament
      reconstruction with or without tendon interposition. The level of intraclass
      correlation among patients clustered within a surgeon showed that individual
      surgeons contribute substantially to determining what procedure type a patient
      undergoes. CONCLUSIONS: In this multiyear, one-state study, current evidence
      demonstrating the equivalent effectiveness of simple trapeziectomy compared with
      more involved alternatives did not result in wide adoption of the technique. This
      finding is consistent with studies in many clinical disciplines that highlight
      the difficulty of influencing clinical practice with available evidence.

PMID- 23542254
TI  - The quality of systematic reviews in hand surgery: an analysis using AMSTAR.
AB  - BACKGROUND: Systematic reviews constitute the top of the "level-of-evidence
      pyramid." Despite their strengths, they have been found to be of varying quality,
      thus raising concerns about their validity and role in influencing clinical
      practice. In the present study, a quality analysis of systematic reviews with a
      focus on hand surgery was performed. METHODS: A PubMed search was performed to
      identify all systematic reviews published up to and including December of 2011 in
      eight surgical journals. Two authors independently reviewed the literature and
      extracted data from included reviews. Discrepancies were resolved by consensus.
      Quality assessment was performed using AMSTAR. RESULTS: The initial search
      retrieved 687 articles. After screening titles and abstracts, 635 articles were
      excluded. Full-text review of the remaining 52 articles resulted in further
      exclusion of 10 articles, leaving 42 systematic reviews for final analysis. A
      significant increase in the number of published systematic reviews over time was
      noted (p = 0.04), with the majority of systematic reviews being published in The
      Journal of Hand Surgery (n = 19) and Plastic and Reconstructive Surgery (n = 12).
      Although a significant improvement in the quality of systematic reviews was noted
      over time (p = 0.01), a median AMSTAR score of 7 indicated the bulk of reviews to
      be of fair to good quality. CONCLUSIONS: The trend to publish more systematic
      reviews in hand surgery is paralleled by an increase in the quality of systematic
      reviews. Nonetheless, increased efforts are indicated to further improve the
      quality of systematic reviews in hand surgery.

PMID- 23542255
TI  - Discussion: the quality of systematic reviews in hand surgery: an analysis using
      AMSTAR.

PMID- 23542256
TI  - Adenotonsillectomy for obstructive sleep apnea in children with syndromic
      craniosynostosis.
AB  - BACKGROUND: The role of adenotonsillectomy in the treatment of obstructive sleep
      apnea in patients with craniosynostosis is not well established. METHODS: A
      retrospective review was conducted of all children with syndromic
      craniosynostosis (Apert, Crouzon, and Pfeiffer syndromes) seen at Boston
      Children's Hospital from January 2001 through April 2011. The primary outcome
      measure was the apnea/hypopnea index before and after adenotonsillectomy.
      RESULTS: There were 47 patients (66 percent Apert syndrome, 19 percent Pfeiffer
      syndrome, and 15 percent Crouzon syndrome) less than 21 years of age (mean, 1.2
      +/- 3.3 years at first visit) who were followed for a mean of 14.6 +/- 8.6 years.
      Of children with at least one polysomnogram, 83 percent had obstructive sleep
      apnea (42 percent severe, 19 percent moderate, 22 percent mild).
      Adenotonsillectomy was performed in 62 percent of patients. Preoperative and
      postoperative polysomnography was performed in 45 percent of children undergoing
      adenotonsillectomy. Following adenotonsillectomy, the mean apnea/hypopnea index
      was not significantly different, and obstructive sleep apnea persisted in 11 of
      13 children. CONCLUSIONS: Obstructive sleep apnea is commonly present in children
      with syndromic craniosynostosis and is a complex disease with airway obstruction
      at several different levels. Adenotonsillectomy often does not improve the
      severity of obstructive sleep apnea in this population.

PMID- 23542257
TI  - Volumetric analysis of simulated alveolar cleft defects and bone grafts using
      cone beam computed tomography.
AB  - BACKGROUND: Cone beam computed tomography allows for a significantly lower
      radiation dose than conventional computed tomographic scans, with generation of
      accurate images of the maxillofacial skeleton. The authors investigated its
      accuracy in the volumetric analysis of alveolar cleft defects and simulated bone
      grafts. METHODS: Five simulated alveolar clefts were created using a burr drill
      in three dry pediatric skulls and filled with simulated bone grafts. Pregrafting
      and postgrafting cone beam computed tomographic scanning of skulls was performed
      using specialized imaging software. The authors compared actual volumes of the
      simulated bone grafts obtained using a water displacement technique with scan
      derived volumes of both the grafts and the defects. RESULTS: The average of the
      five simulated bone grafts calculated by cone beam computed tomography scanning
      was 0.380 ml, which was lower than their mean volume of 0.392 ml calculated by
      water displacement. The percentage difference between measurements ranged from
      2.9 to 8.6 percent (mean, 4.86 percent). The mean of the simulated defects of
      0.399 ml derived from scanning was higher than the actual mean volume of 0.392 ml
      derived by water displacement. The mean difference in defect comparison was 2.52
      percent. There was no statistically significant difference between real volume
      and scan-derived graft and defect volume. CONCLUSIONS: Cone beam computed
      tomography calculation of simulated alveolar cleft and bone graft volume is
      precise and accurate. The volume of bone graft needed to fill alveolar defects
      can be accurately predicted using volume measurements of the bony defect. These
      findings further validate its use in the perioperative assessment of alveolar
      grafting.

PMID- 23542258
TI  - The safe zone for placement of chin implants.
AB  - BACKGROUND: Alloplastic chin augmentation requires the surgeon to predict the
      location of the mental foramen and the origin of the mentalis muscle to avoid the
      postoperative sequelae lower lip parasthesia, lower lip incompetence, or chin
      ptosis. The authors define a safe zone of dissection along the inferior border of
      the mandible for placement of alloplastic chin implants. METHODS: Fourteen fresh
      cadaveric hemifaces were dissected with the aid of loupe magnification.
      Previously described anatomic landmarks were used to identify the origin of the
      mentalis muscle and the location of the mental foramen along the alveolar ridge
      of the mandible. Vertical distances were then measured from the mandibular border
      to the inferior aspect of the mentalis muscle origin and the lower edge of the
      mental foramen to construct the zone of safe dissection. RESULTS: The mentalis
      was identified as a fan-shaped muscle originating from the alveolar process below
      the incisors roots and inserting into the chin just below the labiomental sulcus.
      The mental foramen was located most commonly below the roots of the first and
      second premolars or in the space between the roots. The mentalis origin and the
      mental foramen were 1.8 +/- 0.3 cm and 1.5 +/- 0.2 cm cephalad to the inferior
      edge of the mandible, respectively. These distances define the borders of a safe
      zone above the mandibular border. CONCLUSIONS: A safe zone of dissection for
      alloplastic chin augmentation is identified. This study is applicable to implant
      placement through a submental or an intraoral incision. This safe zone is also
      useful for reconstructive or orthognathic mandible procedures.

PMID- 23542259
TI  - Comparison of three different fat graft preparation methods: gravity separation,
      centrifugation, and simultaneous washing with filtration in a closed system.
AB  - BACKGROUND: Successful long-term volume retention of an autologous fat graft is
      problematic. The presence of contaminating cells, tumescent fluid, and free lipid
      in the graft contributes to disparate outcomes. Better preparation methods for
      the fat graft before transplantation may significantly improve results. METHODS:
      Subcutaneous fat from 22 donors was divided and processed using various graft
      preparation methods: (1) no manipulation control, (2) gravity separation, (3)
      Coleman centrifugation, and (4) simultaneous washing with filtration using a
      commercially available system (Puregraft; Cytori Therapeutics, Inc., San Diego,
      Calif.). Fat grafts from various preparation methods were examined for free
      lipid, aqueous liquid, viable tissue, and blood cell content. Adipose tissue
      viability was determined by measuring glycerol release after agonist induction of
      lipolysis. RESULTS: All test graft preparation methods exhibited significantly
      less aqueous fluid and blood cell content compared with the control. Grafts
      prepared by washing with filtration exhibited significantly reduced blood cell
      and free lipid content, with significantly greater adipose tissue viability than
      other methods. CONCLUSION: Washing with filtration within a closed system
      produces a fat graft with higher tissue viability and lower presence of
      contaminants compared with grafts prepared by alternate methods.

PMID- 23542260
TI  - Brachioplasty outcomes: a review of a multipractice cohort.
AB  - BACKGROUND: Upper arm deformities secondary to massive weight loss or senile
      elastosis have led to an increased demand for aesthetic contouring procedures
      such as brachioplasty. METHODS: The records of all patients who underwent a
      brachioplasty procedure from a multipractice medical center were reviewed.
      Outcomes measured included patient demographics, operative interventions, and
      postoperative course. RESULTS: Ninety-six patients were analyzed. Fifty-three
      patients (55.2 percent) underwent a concomitant procedure, with 53.1 percent
      undergoing arm liposuction at the time of brachioplasty. Major and minor
      complications rates were 17.7 percent and 44.8 percent, respectively. Common
      complications included hypertrophic scarring (24.0 percent) and infection (14.6
      percent). The total revision rate was 22.9 percent, with residual contour
      deformity (40.9 percent of revisions) and hypertrophic scarring (36.4 percent of
      revisions) representing the most common causes for revision. Patients who
      underwent a previous bariatric procedure were at an increased risk of developing
      a major complication (p = 0.02). Concomitant upper arm liposuction and
      concomitant procedures were not associated with a significantly increased
      complication rate. CONCLUSIONS: Brachioplasty, despite being an effective
      treatment for contour irregularities of the upper arm, is associated with
      significant revision and complication rates. Post-bariatric surgery patients
      should be informed of the potential for increased complications. Additional
      procedures performed at the time of brachioplasty do not significantly increase
      complications. Liposuction of the upper arm can be performed safely in
      conjunction with brachioplasty.

PMID- 23542261
TI  - Psychosocial impact of adolescent gynecomastia: a prospective case-control study.
AB  - BACKGROUND: The purpose of this study was to determine the physical and
      psychosocial impact of gynecomastia and its severity on adolescents seeking
      treatment as compared with healthy adolescent males. METHODS: The following
      surveys were administered to adolescents with gynecomastia and healthy male
      controls, aged 12 to 21 years: Short Form-36 Version 2, the Rosenberg Self-Esteem
      Scale, and the Eating Attitudes Test-26. Demographic variables were compared
      between the two groups, and controls were administered a short chest symptoms
      survey. Linear regression models, unadjusted and adjusted for body mass index
      category, were fit to determine the effect of case status and graded severity of
      gynecomastia on survey score. RESULTS: Forty-seven patients with gynecomastia and
      92 male control subjects participated in this study. There was no difference in
      mean age between the groups, although patients with gynecomastia had a
      significantly higher body mass index. Gynecomastia subjects had three lower Short
      Form-36 domain and Rosenberg Self-Esteem Scale scores independent of body mass
      index category as compared with controls, although there was no difference in
      Eating Attitudes Test-26 scores between the groups. Graded gynecomastia severity
      had no effect on survey scores, all independent of body mass index category.
      CONCLUSIONS: Gynecomastia has a significant negative impact on primarily the
      psychosocial well-being of affected adolescent patients, specifically in regard
      to social functioning, mental health, and self-esteem. Psychosocial impact was
      not affected by graded severity of disease. Health care providers and patients
      should be aware of the psychosocial impairments associated with gynecomastia and
      consider early treatment for adolescents suffering from this condition,
      regardless of severity.

PMID- 23542262
TI  - Buttock augmentation with silicone implants: a multicenter survey review of 2226
      patients.
AB  - BACKGROUND: Enhancement of buttock volume with gluteal silicone implants has been
      performed by surgeons for over 30 years, but no studies have examined
      complication rates or outcomes of more than single-surgeon experiences. Numerous
      technical differences in how gluteal augmentation surgery with implants is
      performed also exist, and to date, surgeon preferences for implant plane,
      incisional access, implant type, and drain use have not been quantified. METHODS:
      A 10-question survey was sent to 83 targeted members of the American Society of
      Plastic Surgeons requesting information about number of cases performed, duration
      of surgeon experience, implant placement plane and incisional access, implant
      type, length of typical surgery, use of drains and antibiotic irrigation
      solution, surgeon satisfaction and surgeon assessment of patient satisfaction,
      and number of complications experienced. RESULTS: Nineteen respondents (25
      percent response rate) provided data on 2226 patients. Thirteen respondents (68.4
      percent) favored the intramuscular plane of dissection over the subfascial plane.
      Preference for incisional access was nearly equally divided between a single
      incision in the gluteal cleft (10 respondents) and two incisions separated within
      the cleft (nine respondents). The total number of complications reported was 848
      (38.1 percent). CONCLUSIONS: Gluteal augmentation with silicone implants has
      gained popularity in the last decade. Despite this, no previous studies have
      examined multisurgeon experiences with this procedure to determine complication
      rates or surgeon technical preferences. The authors present data from a survey
      sent to experienced gluteal augmentation surgeons. Advances in technique and
      implant options are needed to improve complication rates experienced with this
      procedure.

PMID- 23542264
TI  - Joseph E. Murray, M.D., nobelist: some personal thoughts.

PMID- 23542265
TI  - The nobler angels of our nature: a tribute to Joseph E. Murray, M.D., 1919 to
      2012.

PMID- 23542266
TI  - Collagen synthesis modulated in wounds treated by pulsed radiofrequency energy.
AB  - BACKGROUND: Chronic wounds are biochemically complex and are associated with
      insufficient cell proliferation, angiogenesis, and extracellular matrix
      remodeling. The mechanisms by which pulsed radiofrequency energy modulates wound
      healing are still unclear. METHODS: Db/db mice were wounded and exposed to pulsed
      radiofrequency energy. Gross closure, cell proliferation, and morphometric
      analysis of CD31-stained wound cross-sections were assessed. The mRNA expression
      of profibrotic factors (transforming growth factor-beta and platelet-derived
      growth factor-A), angiogenetic factors (vascular endothelial growth factor and
      basic fibroblast growth factor), and extracellular matrix components (collagen I
      and alpha-smooth muscle actin) were evaluated by quantitative reverse
      transcriptase polymerase chain reaction. Collagen protein level of the wound was
      determined by Western blot analysis. To test the effect of pulsed radiofrequency
      energy on cell movement in wound healing, cell migration was monitored in
      monolayer dermal fibroblast cultures. The degree of collagen alignment and
      gelation time was quantitatively assessed using image analysis techniques.
      RESULTS: Pulsed radiofrequency energy-treated wounds were characterized by dermal
      cell proliferation and increased collagen synthesis. By contrast, the CD31
      density and the mRNA expression of vascular endothelial growth factor and basic
      fibroblast growth factor showed no significant difference between the pulsed
      radiofrequency energy-treated wounds and the sham group. The pulsed
      radiofrequency energy-treated dermal fibroblast cultures expressed a
      significantly longer gelation time compared with the sham-exposed cultures.
      CONCLUSIONS: Exposing wounds to pulsed radiofrequency accelerated wound healing
      in this diabetic mouse model by means of significantly increasing dermal cell
      proliferation and collagen synthesis. A cellular mechanism behind these
      observations has been proposed.

PMID- 23542267
TI  - Nerve regeneration in rat limb allografts: evaluation of acute rejection rescue.
AB  - BACKGROUND: Successful nerve regeneration is critical to the functional success
      of composite tissue allografts. The present study was designed to characterize
      the effect of acute rejection on nerve regeneration and functional recovery in
      the setting of orthotopic limb transplantation. METHODS: A rat orthotopic limb
      transplantation model was used to evaluate the effects of acute rejection on
      nerve regeneration and motor recovery. Continuous administration of FK506 (full
      suppression), administration of FK506 for the first 8 of 12 weeks (late
      rejection), or delayed administration of FK506/dexamethasone following noticeable
      rejection (early rejection) was used to preclude or induce rejection following
      limb transplantation. Twelve weeks postoperatively, nerve regeneration was
      assessed by means of histomorphometric analysis of explanted sciatic nerve, and
      motor recovery was assessed by means of evoked muscle force measurement in
      extensor digitorum longus muscle. RESULTS: A single episode of acute rejection
      that occurs immediately or late after reconstruction does not significantly alter
      the number of regenerating axonal fibers. Acute rejection occurring late after
      reconstruction adversely affects extensor digitorum longus muscle function in
      composite tissue allografts. CONCLUSIONS: Collected data reinforce that adequate
      immunosuppressant administration in cases of allogeneic limb transplantation
      ensures levels of nerve regeneration and motor functional recovery equivalent to
      that of syngeneic transplants. Prompt rescue following acute rejection was
      further demonstrated not to significantly affect nerve regeneration and
      functional recovery postoperatively. However, instances of acute rejection that
      occur late after reconstruction affect graft function. In total, the present
      study begins to characterize the effect of immunosuppression regimens on nerve
      regeneration and motor recovery in the setting of composite tissue allografts.

PMID- 23542269
TI  - Clinical application of the internal mammary artery perforator flap in head and
      neck reconstruction.
AB  - BACKGROUND: The skin texture of the internal mammary artery perforator flap
      closely resembles that in the face and neck, making it the perfect source of
      tissue for head and neck reconstruction. In this article, the authors describe
      their experience in recent application of this flap in head and neck
      reconstruction and evaluate its pros and cons. METHODS: A total of 15 patients
      (three women and 12 men) with a mean age of 58.6 years received an internal
      mammary artery perforator flap for head and neck defect repair from April of 2007
      to August of 2011. There were 11 internal mammary artery perforator pedicle flaps
      and four internal mammary artery perforator free flaps. RESULTS: Flap size ranged
      from 5 * 3 cm to 15 * 8 cm, pedicle length ranged from 3 to 6 cm, and 14 of 15
      flaps (93.3 percent) had a sizable perforator identified during dissection. In
      the female patient who had no sizable perforator, the originally intended free
      flap was transformed to a platysma myocutaneous flap, which served as a backup
      procedure, extending from the same surgical incision. All of the transfers were
      successful. The donor sites were closed primarily in all patients except one, who
      received a split-thickness skin graft for a 15 * 8-cm donor defect. CONCLUSION:
      With excellent skin color and tissue texture matching and minimal donor-site
      morbidity, the internal mammary artery perforator flap is emerging as a potential
      alternative reconstructive tool for the head and neck region.

PMID- 23542268
TI  - Novel animal model of calvarial defect: part IV. Reconstruction of a calvarial
      wound complicated by durectomy.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been
      shown to be an effective therapy in the acute calvarial defect wound and in
      calvarial defects complicated by chronic scar and radiation. The authors assessed
      the effectiveness of rhBMP-2-mediated bone regeneration in calvarial defects
      complicated by durectomy. METHODS: Sixteen adult New Zealand White rabbits
      underwent subtotal calvariectomy and dural removal, followed by dural repair and
      reconstruction in one of four groups: empty (n = 3), vehicle (buffer solution on
      an absorbable collagen sponge, n = 2), autologous graft (n = 3), or rhBMP-2
      repair (rhBMP-2/absorbable collagen sponge, n = 8). Animals underwent computed
      tomographic imaging at 0, 2, 4, and 6 weeks postoperatively, followed by
      euthanasia and histologic analysis. Percent healing was determined by three
      dimensional analysis. A 4 * 3 mixed model analysis of variance was performed on
      healing versus treatment group/postoperative time. RESULTS: The rhBMP
      2/absorbable collagen sponge and autograft repair groups had 51.4 and 37.3
      percent healing, respectively, at 6 weeks; empty and vehicle control groups had
      7.8 and 17.9 percent healing, respectively, at 6 weeks. Compared with immediate
      favorable reconstruction (96.8 percent healing), rhBMP-2 in this setting was
      significantly less effective (p = 0.001). Bone in the rhBMP-2/absorbable collagen
      sponge group was compact and cellular but appeared only over the intact sagittal
      sinus and irregularly within the absorbable collagen sponge. CONCLUSIONS:
      Although promising in the acute calvarial wound and other complex defects, rhBMP
      2 therapy is less effective in reconstruction following dural compromise. Future
      studies using additional growth factors and cell therapy may improve results in
      this especially difficult scenario.

PMID- 23542270
TI  - A functional magnetic resonance imaging paradigm to identify distinct cortical
      areas of facial function: a reliable localizer.
AB  - BACKGROUND: Irreversible facial paralysis can be surgically treated by importing
      both a new neural and a new motor muscle supply. Various donor nerves can be
      used. If a nerve supply other than the facial nerve is used, the patient has to
      adapt to generate a smile. If branches of the fifth cranial nerve are used, the
      patient has to learn to clench teeth and smile. Currently, controversy exists
      regarding whether a patient develops a spontaneous smile if a nerve other than
      the facial nerve is used. The authors postulate that brain adaptation in facial
      palsy patients can occur because of neural plasticity. The authors aimed to
      determine whether functional magnetic resonance imaging could topographically
      differentiate activity between the facial nerve- and the trigeminal nerve-related
      cortical areas. METHODS: A new paradigm of study using functional magnetic
      resonance imaging based on blood oxygen level-dependent signal activation was
      tested on 15 voluntary healthy subjects to find a sensitive localizer for teeth
      clenching and smiling. Subjects smiled to stimulate the facial nerve-related
      cortex, clenched their jaws to stimulate the trigeminal nerve-related cortex, and
      tapped their finger as a control condition. RESULTS: Smiling and teeth clenching
      showed distinct and consistent areas of cortical activation. Trigeminal and
      facial motor cortex areas were found to be distinct areas with minimal
      overlapping. CONCLUSIONS: The authors successfully devised a functional magnetic
      resonance imaging paradigm effective for activating specific areas corresponding
      to teeth clenching and smiling. This will allow accurate mapping of cortical
      plasticity in facial reanimation patients.

PMID- 23542272
TI  - Outcome after pollicization: comparison of patients with mild and severe
      longitudinal radial deficiency.
AB  - BACKGROUND: Pollicization of the index finger is a well-established treatment in
      type IIIB to type V hypoplastic thumbs. However, there is a lack of quantitative
      outcome studies, and little is known about the outcome differences between
      patients with mild and severe longitudinal radial deficiencies. Therefore, the
      aim of this study was to quantitatively assess and compare outcome after
      pollicization in severe and mild longitudinal radial deficiency and compare
      outcome to healthy controls. METHODS: In total, the authors included 24 patients
      with 30 affected hands. The study group consisted of 16 male patients and eight
      female patients with a mean age of 14 years. Median time between pollicization
      and evaluation was 9.4 years. Active and passive range of motion, extrinsic and
      intrinsic strength, sensibility, and patient and parent satisfaction were
      measured in patients with mild and severe longitudinal radial deficiency. Means
      are expressed as a percentage of normative data, and standard deviations and
      ranges were calculated. The independent samples t test was used to compare means
      between groups. RESULTS: In the overall pollicization group with associated
      longitudinal radial deficiency, range of motion and strength were significantly
      diminished compared with normative data. In severe longitudinal radial
      deficiency, all strength measurements were significantly more affected than in
      mild longitudinal radial deficiency. CONCLUSIONS: Overall, range of motion and
      strength of pollicizations were diminished compared with normative data. In
      severe longitudinal radial deficiency, this was even more pronounced. Despite
      this outcome, patients and their parents were very satisfied with function and
      appearance of the new thumb.

PMID- 23542271
TI  - Vascular anatomy and clinical application of anterolateral leg perforator flaps.
AB  - BACKGROUND: There is a dearth of detailed published work on anterolateral leg
      perforators. The authors fully documented the vascular basis of the anterolateral
      leg perforator flap and report its use in reconstruction of distal extremities.
      METHODS: Anterolateral leg perforators were investigated in 25 fresh cadavers and
      10 casts of arteries. Fresh cadavers were injected with a standardized injection
      of lead oxide for three-dimensional visualization reconstruction using
      multidetector-row computed tomography and professional software. The origin,
      course, and distribution of the perforators in the anterolateral leg region were
      observed. Between March of 2008 and March of 2012, 15 free superficial peroneal
      artery perforator flaps were used for reconstruction of distal limbs. Flap size
      varied from 3.5 * 4.0 cm to 11 * 5 cm, with a uniform thickness of 3 mm. RESULTS:
      There were 7 +/- 3.0 perforators in the anterolateral leg. The average external
      diameter was 0.7 +/- 0.2 mm. Each perforator supplied an average area of 33 +/-
      8.0 cm. Extensive anastomoses were found between the superficial peroneal artery
      perforators and multiple adjacent source arteries. All cases were repaired
      successfully without any complications. The clinical results were satisfactory
      after 3 to 12 months of follow-up. The flaps were considered cosmetically
      acceptable by both patients and doctors. CONCLUSIONS: The anterolateral leg
      perforator flaps have a consistent, reliable blood supply and good texture. The
      donor site not only supplies a thin skin flap but also provides the option of
      harvesting cross-boundary proximally or distally based perforator flaps that
      could be useful for repairing widespread traumatic soft-tissue defects.

PMID- 23542273
TI  - Reverse bipaddle posterior interosseous artery perforator flap.
AB  - BACKGROUND: The reverse posterior interosseous artery perforator flap is useful
      for covering defects over the distal forearm, wrist, and hand, but some of its
      major limitations include short vascular pedicle, inadequate distal reach,
      difficult pedicle dissection, and risk of venous congestion. Some of these
      drawbacks have been overcome with refinements over the years, but the problems of
      donor-site morbidity and inability to reconstruct multiple subunits of the hand
      in a single stage remain. The authors developed a variant of the original
      distally based flap to extend its applications and minimize donor-site morbidity.
      METHODS: Eleven cases of reverse bipaddle posterior interosseous artery
      perforator flap reconstruction were reviewed. Defect locations included the first
      web space, proximal thumb, dorsum of the hand, palm, wrist, and the radial or
      ulnar half of the hand. RESULTS: Eleven patients were successfully treated with
      the bipaddle posterior interosseous artery perforator flap with no major
      complications. In seven cases, the type A chain-like variant was used to cover
      defects involving two different units of the hand. In four patients, the type B
      "kiss" pattern was required to resurface a large defect of a single unit of the
      hand. In all type B cases, the donor site was closed directly. All patients were
      satisfied with their outcomes. CONCLUSIONS: The reverse bipaddle posterior
      interosseous artery perforator flap is an excellent method of covering large
      defects of the hand involving multiple subunits. The authors confirm its vascular
      reliability and highlight several recommendations for skin island location,
      pedicle dissection, and flap raising and insetting.

PMID- 23542275
TI  - Normal nasolabial anatomy in infants younger than 1 year of age.
AB  - BACKGROUND: Normal nasolabial anatomy has received little attention in infants
      younger than 1 year. However, the notion of an ideal lip and nose is critical to
      reconstruction of this region, especially for cleft lip and nose repair. The
      purpose of this study was to quantitatively define the normal nasolabial anatomy
      in a series of infants younger than 1 year. METHODS: A prospective analysis was
      performed of infants aged 0 to 12 months from 2011 to 2012. Plaster molds of the
      nasolabial region were produced from each subject. Anthropometric measurements
      were performed by two independent, blinded reviewers. Results were compiled and
      compared statistically using the two-tailed t test and analysis of variance with
      the post hoc Tukey honestly significant difference test. Correlation coefficients
      were calculated for the relationship of age and weight to nasolabial
      measurements. RESULTS: A total of 34 infants were included (mean age, 8.7 months;
      girls, n = 11). Ten anthropometric measurements of the nasolabial region were
      performed. Nasal length in boys was significantly longer than in girls (p <
      0.05). With the exception of alar base width (p < 0.001), philtrum column height
      (p < 0.05), and cutaneous upper lip height (p < 0.01), ethnicity had no effect on
      nasolabial measurements. Alar thickness and nares circumference correlated
      positively with age and weight (p < 0.05). CONCLUSIONS: The normal nasolabial
      morphology is anthropometrically described in a population of infants younger
      than 1 year. Measurements were similar between boys and girls, and alar thickness
      and nostril circumference correlated with increasing age and weight.

PMID- 23542274
TI  - Trend of recovery after simple decompression for treatment of ulnar neuropathy at
      the elbow.
AB  - BACKGROUND: Although numerous studies have investigated long-term outcomes after
      surgical treatment of ulnar neuropathy at the elbow with simple decompression, no
      study has evaluated the trend of postoperative recovery. The authors assessed
      timing of recovery after simple decompression for ulnar neuropathy at the elbow.
      METHODS: The five-center Surgery of the Ulnar Nerve Study Group prospectively
      recruited 58 consecutive subjects with ulnar neuropathy at the elbow and treated
      them with simple decompression. Patients were evaluated preoperatively and at 6
      weeks, 3 months, 6 months, and 1 year postoperatively. Patient-rated outcomes
      questionnaires included the Michigan Hand Questionnaire; the Disabilities of the
      Arm, Shoulder and Hand questionnaire; and the Carpal Tunnel Questionnaire.
      Functional tests used were grip strength, key pinch strength, two-point
      discrimination, and Semmes-Weinstein monofilament testing. Postoperative
      improvement was assessed at each time point to establish the trend of recovery in
      reaching a plateau. RESULTS: Significant patient-reported symptomatic and
      functional recovery occurred over the first 6 weeks postoperatively as
      represented by improvements in questionnaire scores. Symptomatic recovery
      occurred earlier than functional recovery as measured by sensory and strength
      testing and the work domain of the Michigan Hand Questionnaire. Improvement in
      patient-reported outcomes continued and reached a plateau at 3 months, whereas
      measured strength and sensory recovery continued over 12 months. CONCLUSION: The
      greatest clinical improvement after simple decompression for ulnar neuropathy at
      the elbow, according to questionnaire scores, occurs in the first 6 weeks
      postoperatively and reaches a plateau by 3 months.

PMID- 23542276
TI  - Analysis of routine intensive care unit admission following fronto-orbital
      advancement for craniosynostosis.
AB  - BACKGROUND: Intensive care unit admission following fronto-orbital advancement
      for craniosynostosis is routine at most institutions. The authors determined the
      frequency of postoperative events requiring intensive care unit care that justify
      this practice. METHODS: Infants with craniosynostosis who underwent primary
      fronto-orbital advancement at a single institution from 1997 to 2011 were
      included. Patient demographics, operative factors, and hemodynamic outcomes were
      recorded. Adverse postoperative events/interventions were graded as none (group
      I); minor (group II), easily managed on a surgical floor; or major (group III),
      requiring intensive care unit care. RESULTS: One hundred seven infants were
      included. Average length of hospitalization was 3.7 +/- 1.6 days, with 1.3 +/-
      1.0 days in the intensive care unit and 2.4 +/- 1.0 days on the floor. Seventy
      eight patients (72.9 percent) were categorized into group I, 24 (22.4 percent)
      into group II, and five (4.7 percent) into group III. Major events/interventions
      included prolonged intubation (n = 2), reintubation (n = 2), and continuous
      positive airway pressure support (n = 1). Preexisting end-organ dysfunction was
      significantly associated with group III patients, who also had significantly
      higher intraoperative blood loss requiring greater resuscitation. Mean daily
      charges were $7652.33 (10.9 percent of total charges) for intensive care unit
      care and $2470.62 (6.9 percent of total charges) for floor care. CONCLUSIONS: In
      this study, 4.7 percent of patients had event/interventions requiring intensive
      care unit care after fronto-orbital advancement. Predictors included preexisting
      end-organ dysfunction and higher intraoperative blood loss requiring greater
      resuscitation. Financial savings from selective postoperative intensive care unit
      admission may not outweigh the potential cost of an emergent event on the
      surgical floor.

PMID- 23542277
TI  - Autologous injectable dermis: a clinical and histological study.
AB  - BACKGROUND: No perfect solution yet exists for dermal fillers. The authors
      hypothesized that autologous dermis can be processed in an operator-friendly
      manner and adopted in selected patients as a filler, following the principle of
      replacing "like with like." METHODS: The authors designed a prototype "cutting
      chamber" to morsel dermis into an injectable form. Autologous injectable dermis
      grafting was performed in 16 patients who underwent lip or labionasal fold
      correction concomitant with abdominoplasty or cesarean scar correction; patient
      dermis was used for the donor graft. Furthermore, injectable dermis grafting was
      performed in the subcutaneous tissue of three patients undergoing multistage
      reconstructive procedures for obesity. The grafts were harvested and examined
      histologically at 3, 7, and 12 months. RESULTS: Dermis processing and injection
      proved feasible with limited effort. All 16 patients presented good volume
      maintenance by 12 months. Two reported transient palpable firmness for the first
      6 months, which subsequently resolved. Histological examination of processed and
      injected dermis showed volume maintenance over time, effective revascularization
      of the mass, and structural reorganization with collagen bundles and nested
      fibroblasts reminiscent of reticular dermis. A transient inflammatory reaction
      was observed, consistent with the expected healing events. CONCLUSIONS: Use of
      autologous dermis as a filler substance for both aesthetic and reconstructive
      procedures appears to be a feasible option. It could be advised for patients
      requiring filler correction who undergo concomitant procedures involving excision
      of potential donor dermis.

PMID- 23542278
TI  - Dermal filler complications from unknown biomaterials: identification by
      attenuated total reflectance spectroscopy.
AB  - BACKGROUND: In the last decade, an increase in complications related to dermal
      filler injections has been reported, especially in patients who underwent
      multiple treatments with different products. Imaging or histological examinations
      may suggest what kind of substance was used, but none can precisely identify the
      biomaterial. The aim of this study was to evaluate the use of Fourier transform
      infrared spectroscopy, using an attenuated total reflectance cell, in the
      identification of unknown dermal fillers. METHODS: In the preclinical study,
      samples from different manufacturers were analyzed according to attenuated total
      reflectance spectroscopy using the Nicolet 8700 FT-IR spectrophotometer
      (resolution, 0.125 cm; Thermo Fisher Scientific, Inc., Madison, Wis.). Spectra of
      each biomaterial were collected and included in a reference database. In the
      clinical study, seven patients affected by severe complications due to multiple
      injections with unknown fillers provided a sample of the pathological tissue for
      the analysis. RESULTS: Two granulomas, two infiltrated tissues, and three
      abscesses were studied. Attenuated total reflectance/Fourier transform infrared
      analysis of pathological tissues revealed the presence of absorption bands absent
      in the healthy tissue. Comparison of these bands to the filler database made it
      possible to identify the dermal fillers injected. CONCLUSIONS: This pilot study
      has demonstrated the absolute validity of the application of infrared
      spectroscopy in attenuated total reflectance for the determination of infiltrated
      biomaterial. The knowledge of the previously injected fillers may be crucial to
      selecting the appropriate medical or surgical treatment as well as to solving
      medical-legal issues.

PMID- 23542279
TI  - A multivariate regression analysis of panniculectomy outcomes: does plastic
      surgery training matter?
AB  - BACKGROUND: Panniculectomy can improve quality of life in morbidly obese
      patients, but its functional benefits are counterbalanced by relatively high
      complication rates. The authors endeavored to determine the impact of plastic
      surgery training on panniculectomy outcomes. METHODS: A retrospective review was
      performed of the prospectively maintained American College of Surgeons National
      Surgical Quality Improvement Program database for all patients undergoing
      panniculectomy from 2006 to 2010. Patient demographic details, surgeon specialty
      training, and 30-day outcomes were assessed. RESULTS: A total of 954
      panniculectomies meeting inclusion criteria were identified. Plastic surgeons
      performed 694 (72.7 percent) of the procedures, and 260 (27.3 percent) were
      performed by nonplastic surgeons. Nonplastic surgeons had significantly higher
      rates of overall complications (23.08 percent versus 8.65 percent; p < 0.001) and
      wound infections (12.69 percent versus 5.33 percent; p < 0.001) than plastic
      surgeons. Average operative time for plastic surgeons was significantly longer
      than that for nonplastic surgeons (3.00 +/- 1.48 hours versus 1.88 +/- 0.93
      hours; p < 0.001). Risk-adjusted multivariate regression showed that undergoing a
      panniculectomy by a nonplastic surgeon was a significant predictor of overall
      postoperative complications (odds ratio, 2.09; 95 percent CI, 1.35 to 3.23) and
      wound infection (odds ratio, 1.73; 95 percent CI, 1.004 to 2.98). Subgroup
      analysis of propensity-matched samples supported this finding. CONCLUSION:
      Multivariate regression analysis of National Surgical Quality Improvement Program
      data showed that panniculectomy performed by plastic surgeons results in lower
      rates of overall postoperative complications compared with that performed by
      nonplastic surgeons.

PMID- 23542280
TI  - Practical details of nasal reconstruction.
AB  - LEARNING OBJECTIVES: Learning Objectives: After reading this article, the
      participant should be able to: 1. Examine a nasal defect to determine its true
      dimension and outline and plan the appropriate timing of reconstruction. 2.
      Develop a surgical plan to restore normal dimension, volume, symmetry, and
      outline. 3. Determine the need for local versus regional flap repair. 4.
      Understand and apply aesthetic principles of nasal reconstruction. 5. Use exact
      surgical templates to determine the position, dimension, and outline transferred
      tissues. 6. Distinguish the indications for a two- or three-stage forehead flap.
      7. Use the modified folded forehead flap technique with primary and delayed
      primary support replacement. 8. Understand an approach to the late revision.
      SUMMARY: This article and accompanying video discuss a step-by-step approach to
      the reconstruction of a full-thickness heminasal defect in a demanding attractive
      woman who developed necrosis after cosmetic rejuvenation of the nasolabial fold
      by filler injection. Aesthetic principles were applied to develop a surgical plan
      to define the timing of reconstruction and true defect for repair with a full
      thickness folded forehead flap transferred in three stages using a modified
      folded forehead flap for lining and primary and delayed primary support with a
      late revision to further refine nasal landmarks.

PMID- 23542281
TI  - Implementation of an emergency response protocol for overseas surgical outreach
      initiatives.
AB  - BACKGROUND: Many health organizations sponsor overseas surgical outreach
      initiatives, yet none has published a standardized protocol to prevent and manage
      unforeseen emergencies. Surgeons, anesthesiologists, nurses, and administrators
      working together on a brief overseas humanitarian initiative-benefit from
      education and training to maximize their collective emergency responsiveness.
      This article outlines the emergency response protocol instituted by the Global
      Smile Foundation, a 501(c)(3) nonprofit global outreach organization providing
      comprehensive cleft care for the past 25 years. METHODS: The Global Smile
      Foundation emergency response protocol was constructed to provide all team
      members resources and training needed to emulate the high emergency response
      standards of developed nations. In this article, the authors share their
      education/training strategy, emergency "crash" cart inventory, site-specific
      safety checklist, and team member roles and responsibilities during various
      emergencies. RESULTS: The authors' protocol emphasizes equipment portability,
      location-specific adaptability, clear workflow/communication, and standardized
      team roles. On-site training is likewise portable, standardized, reproducible,
      efficient, and adaptive to each setting. These characteristics make the authors'
      protocol widely adoptable. CONCLUSIONS: Most morbidity and mortality during
      overseas surgical outreach initiatives result from unfamiliarity with the host
      hospital and other team members during operative (e.g., airway, bleeding,
      circulatory, anesthetic) or location-based (e.g., power outage, fire, oxygen
      shortage) emergencies. These complications are prevented and managed with
      aggressive team education and training. The Global Smile Foundation protocol
      adapts to the uncertainties of providing medical care in underresourced settings
      and reflects experience accumulated over the past quarter century. It is the
      authors' hope that other humanitarian outreach groups will adopt, customize, and
      build on these basic tenets.

PMID- 23542282
TI  - Grading lipoaspirate: is there an optimal density for fat grafting?

PMID- 23542283
TI  - Revision otoplasty: an algorithm.

PMID- 23542284
TI  - Reply: revision otoplasty: an algorithm.

PMID- 23542285
TI  - Combined use of acellular dermal matrix and supraclavicular artery island flap
      for oropharyngeal reconstruction.

PMID- 23542286
TI  - Reply: combined use of acellular dermal matrix and supraclavicular artery island
      flap for oropharyngeal reconstruction.

PMID- 23542287
TI  - A prospective randomized study comparing two different expander approaches in
      implant-based breast reconstruction: one stage versus two stages.

PMID- 23542288
TI  - Observations on the survival and neovascularization of fat grafts interchanged
      between C57BL/6-gfp and C57BL/6 mice.

PMID- 23542289
TI  - Adipocyte damage in relation to different pressures generated during manual
      lipoaspiration with a syringe.

PMID- 23542290
TI  - Reply: adipocyte damage in relation to different pressures generated during
      manual lipoaspiration with a syringe.

PMID- 23542291
TI  - Misrepresentation of scholarly works by integrated plastic surgery applicants.

PMID- 23542292
TI  - Reply: misrepresentation of scholarly works by integrated plastic surgery
      applicants.

PMID- 23542293
TI  - The birth prevalence of cleft lip and palate in canadian aboriginal peoples: a
      registry study.

PMID- 23542294
TI  - Updating the epidemiology of isolated cleft palate.

PMID- 23542295
TI  - Extramammary Paget's Disease in Males: A Caveat for the Plastic Surgeon.

PMID- 23542296
TI  - Facial flap contouring using a sinus microdebrider.

PMID- 23542297
TI  - A malignant late seroma 20 years after breast cancer and saline implants.

PMID- 23542298
TI  - The clinical conundrum of perioperative pain management in patients with opioid
      dependence: lessons from two cases.

PMID- 23542299
TI  - Definitive evidence of rectus abdominis preservation and function after bilateral
      DIEP breast reconstruction.

PMID- 23542300
TI  - S-shaped brachioplasty: an effective technique to correct excess skin and fat of
      the upper arm.

PMID- 23542301
TI  - Personal approach to the correction of prominent ears.

PMID- 23542302
TI  - Ultherapy shrinks nasal skin after rhinoplasty following failure of conservative
      measures.

PMID- 23542303
TI  - Regenerative surgery for the definitive repair of chronic ulcers: a series of 34
      cases treated with platelet-derived growth factors.

PMID- 23542304
TI  - Three-dimensional surface-imaging systems.

PMID- 23542305
TI  - Protecting a plastic surgeon's reputation: damage control for dishonest online
      reviews.

PMID- 23542306
TI  - Usability testing of AsthmaWise with older adults.
AB  - There are many reasons why online self-management education is attractive to both
      patients and providers. AsthmaWise, an online self-management program, was
      developed using a Moodle platform, to enable older adults to learn asthma self
      management skills. This study aimed to improve AsthmaWise through conducting:
      usability testing with a sample of end users; a cognitive walk-through undertaken
      by an independent health researcher; and assessment of content readability. A
      Perceived Health Web Site Usability Questionnaire score of 67% was achieved,
      indicating that there were usability issues that needed to be addressed. The
      cognitive walk-through and readability assessment identified unique issues that
      were not identified through usability testing with end users. The testing process
      allowed issues to be identified and rectified before piloting AsthmaWise,
      creating a more accessible and refined end product. The involvement of the site
      designer in the testing process was valuable and is highly recommended. This
      study shows that usability testing involving both end users and experts is an
      essential part of the design process that is relatively easy and inexpensive to
      undertake and can be effectively conducted by a nonexpert.

PMID- 23542307
TI  - Identifying at-risk nursing students using a midcurricular examination.
AB  - The purpose of this study was to investigate the usefulness of the midcurricular
      HESI examination in identifying at-risk students early in their nursing program.
      The sample included baccalaureate nursing graduates from two university programs
      in the southeastern United States (n = 256). A quasi-experimental design was used
      to determine how well the midcurricular HESI predicted outcomes on the HESI E(2)
      and the NCLEX-RN passing status while controlling for demographic and
      institutional covariates. The study used logistic regression and multiple linear
      regression to analyze the hypotheses. The midcurricular HESI examination was
      found to be a statistically significant predictor of NCLEX-RN outcome both before
      (P = .044) and after (P = .041) controlling for demographic factors. The study
      further found a statistically significant relationship between the midcurricular
      HESI and the HESI E(2) examinations (P < .001). In the post hoc analyses,
      students from the Accelerated and Fast Track degree programs scored significantly
      higher than did students in the Traditional Track on the midcurricular HESI
      examination. There were no statistically significant differences in HESI E(2)
      scores or NCLEX-RN outcomes among the degree tracks. As anticipated, there was a
      statistically significant difference in both midcurricular HESI (P < .043) and
      HESI E(2) (P < .016) scores between students who passed and those who failed
      NCLEX-RN. This study indicates that the midcurricular HESI examination is very
      useful in predicting outcomes in baccalaureate nursing education programs.

PMID- 23542308
TI  - Preparative isolation and structural characterization of sucrose ester isomers
      from oriental tobacco.
AB  - To date, the structures of the sucrose tetraester (STE) isomers, a main kind of
      sucrose esters (SEs) in Solanum, have not been conclusively assigned. In this
      study, three groups of STE isomers with the molecular weight 650, 664 and 678
      (designated as STE I, STE II and STE III, respectively) have been isolated and
      purified from the oriental tobacco-Komotini Basma using a semi-preparative RP
      HPLC method. The full characterization of the isomers in the three groups of STE
      were investigated for the first time by MS (HRMS, MS(2)) and NMR ((1)H, (13)C,
      HSQC) spectroscopy combined with alkaline hydrolysis and STE derivation
      experiments. The STE III (a single compound) was confirmed as a known sucrose
      tetraester. Furthermore, the STE II was found to contain three isomers and the
      structures were first unambiguously established as 6-O-acetyl (2,3 or 2,4 or 3,4)
      di-O-3-methylvaleryl-(4 or 3 or 2)-O-2-methylbutyryl-alpha-d-glucopyranosyl-beta
      d-fructofuranoside. Finally, the STE I was discovered to contain seven isomers
      and the structures were elucidated as 6-O-acetyl (2 or 3 or 4)-O-3-methylvaleryl
      (3,4 or 2,4 or 2,3)-di-O-2-methylbutyryl-alpha-d-glucopyranosyl-beta-d
      fructofuranoside, 6-O-acetyl (2 or 3 or 4)-O-3-methylvaleryl-(3,4 or 2,4 or 2,3)
      di-O-isovaleryl-alpha-d-glucopyranosyl-beta-d-fructofuranoside and 6-O-acetyl
      (2,3 or 2,4 or 3,4)-di-O-3-methylvaleryl-(4 or 3 or 2)-O-isobutyryl-alpha-d
      glucopyranosyl-beta-d-fructofuranoside (one of the 3 isomers).

PMID- 23542309
TI  - Protection from diabetic cardiomyopathy - putative role of the retinoid receptor
      mediated signaling.

PMID- 23542310
TI  - Identification and characterization of a transient outward K+ current in human
      induced pluripotent stem cell-derived cardiomyocytes.
AB  - BACKGROUND: The ability to recapitulate mature adult phenotypes is critical to
      the development of human induced pluripotent stem cell-derived cardiomyocytes
      (hiPSC-CM) as models of disease. The present study examines the characteristics
      of the transient outward current (Ito) and its contribution to the hiPSC-CM
      action potential (AP). METHOD: Embryoid bodies were made from a hiPS cell line
      reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to
      record APs from beating-clusters (BC) and patch-clamp techniques were used to
      record Ito in single hiPSC-CM. mRNA levels of Kv1.4, KChIP2 and Kv4.3 were
      quantified from BCs. RESULTS: BCs exhibited spontaneous beating (60.5+/-2.6 bpm)
      and maximum-diastolic-potential (MDP) of 67.8+/-0.8 mV (n=155). A small 4
      aminopyridine-sensitive phase-1-repolarization was observed in only 6/155 BCs. A
      robust Ito was recorded in the majority of cells (13.7+/-1.9 pA/pF at +40 mV;
      n=14). Recovery of Ito from inactivation (at -80 mV) showed slow kinetics
      (tau1=200+/-110 ms (12%) and tau2=2380+/-240 ms (80%)) accounting for its minimal
      contribution to the AP. Transcript data revealed relatively high expression of
      Kv1.4 and low expression of KChIP2 compared to human native ventricular tissues.
      Mathematical modeling predicted that restoration of IK1 to normal levels would
      result in a more negative MDP and a prominent phase-1-repolarization. CONCLUSION:
      The slow recovery kinetics of Ito coupled with a depolarized MDP account for the
      lack of an AP notch in the majority of hiPSC-CM. These characteristics reveal a
      deficiency for the development of in vitro models of inherited cardiac arrhythmia
      syndromes in which Ito-induced AP notch is central to the disease phenotype.

PMID- 23542311
TI  - Abandoning the ship: spontaneous mass exodus of Clinostomum complanatum
      (Rudolphi, 1814) progenetic metecercariae from the dying intermediate host
      Trichogaster fasciatus (Bloch & Schneider, 1801).
AB  - The dramatic and spontaneous exodus of live Clinostomum complanatum progenetic
      metacercaria from the gill slits of the dying intermediate host, Trichogaster
      fasciatus is reported. Basic water parameter tests for dissolved oxygen, pH and
      temperature revealed slightly lower level of dissolved oxygen in tank water used
      for water change. To the best of our knowledge, it is the first report of a
      digenean metacercariae, en mass leaving their intermediate host, upon its death
      in search of an alternative host to support their survival and help in continuing
      their life cycle.

PMID- 23542312
TI  - Magnetic resonance imaging after translabyrinthine complete excision of
      vestibular schwannomas.
AB  - The objective of this study is to determine whether magnetic resonance imaging
      (MRI) at 2 years following complete vestibular schwannoma (VS) excision using a
      translabyrinthine approach is sufficient to detect recurrent tumor. The study is
      set in a tertiary referral skull base unit. A service evaluation of a prospective
      database identified patients who underwent complete translabyrinthine VS excision
      with prospectively recorded MRI results at 2 and 5 years following surgery. The
      main outcome measures were evidence of tumor recurrence on MRI at 2 and 5 years
      after surgery. Of 314 patients in the study, all patients where MRI was reported
      to show no recurrence at 2 years (97%) also had no signs of recurrence on MRI at
      5 years. All eight patients with MRI suspicious of recurrence (linear enhancement
      of internal auditory canal [IAC]) at 2 years had no progression on MRI at 5 to 15
      years. One patient had evidence of definite recurrence (nodular enhancement of
      IAC) at 2 years, who went on to have radiosurgery at 8 years. Where patients have
      MRI with no linear enhancement of the IAC at 2 years, no further imaging is
      required. Where linear enhancement is seen, no change in enhancement at 5 years
      is reassuring and no further imaging is required.

PMID- 23542313
TI  - Spontaneous cholecysto-cutaneous fistula complicating carcinoma of the gall
      bladder: a case report.
AB  - Most cholecystocutaneous fistulas are postoperative complications of liver and
      biliary tract surgery or trauma. External biliary fistulas rarely occur
      spontaneously as a result of intrahepatic abscess (pyogenic or parasitic),
      necrosis or perforation of the gallbladder, or other inflammatory process
      involving the biliary tree. A cholecystocutaneous fistula as a presentation of an
      underlying cancer arising from the gall bladder is an extremely uncommon finding.
      Over the past 50 years fewer than 20 cases of spontaneous cholecystocutaneous
      fistulas have been described in the medical literature but so far there has been
      no published report of a cholecystocutaneous fistula arising from adenocarcinoma
      of gall bladder. We here report a case of a patient presenting with spontaneous
      cholecystocutaneous fistula from cancer of gall bladder.

PMID- 23542314
TI  - Fetal Haemoglobin and beta-globin Gene Cluster Haplotypes among Sickle Cell
      Patients in Chhattisgarh.
AB  - BACKGROUND: Foetal Haemoglobin (HbF) is the best-known genetic modulator of
      sickle cell anaemia, which varies dramatically in concentration in the blood of
      these patients. The patients with SCA display a remarkable variability in the
      disease severity. High HbF levels and the beta-globin gene cluster haplotypes
      influence the clinical presentation of sickle cell disease. To identify the
      genetic modifiers which influence the disease severity, we conducted a beta
      globin haplotype analysis in the sickle cell disease patients of Chhattisgarh.
      AIM: The foetal haemoglobin and the beta-globin gene haplotypes of the sickle
      cell trait and the sickle cell disease patients from Chhattisgarh were
      investigated. MATERIALS AND METHOD: A total of 100 sickle cell patients (SS), 50
      sickle cell trait patients (AS) and 50 healthy control individuals were included
      in the present study. The distribution of the beta-globin gene haplotype was done
      by the PCR-RFLP method. RESULT: PCR-RFLP showed that the homozygous Arab-Indian
      haplotype (65%) was the most frequent one, followed by the heterozygous Arab
      Indian haplotype (11%) in the sickle cell patients (SS), while the AS patients
      had a higher frequency of the heterozygous Arab-Indian haplotype (38%) in
      comparison to homozygous one (32%). Four atypical haplotypes, 3 Benin and 1
      Cameroon were also observed, although they were in lower frequencies. In the
      present study, the HbF levels were higher in the AS and the SS patients, with one
      or two Arab-Indian haplotypes as compared to the other haplotypes. CONCLUSION:
      The presence of the Arab-Indian haplotype as the predominant haplotype might be
      suggestive of a gene flow to/from Saudi-Arabia or India and it was associated
      with higher HbF levels and a milder disease severity.

PMID- 23542317
TI  - Correlation of Brain Biomarker Neuron Specific Enolase (NSE) with Degree of
      Disability and Neurological Worsening in Cerebrovascular Stroke.
AB  - Stroke is the third major cause of death and foremost cause of disability
      worldwide. Cerebrovascular stroke remains largely a clinical diagnosis. The use
      of biomarkers in diagnosing stroke and assessing prognosis is an emerging and
      rapidly evolving field. The study aimed to investigate the predictive value of
      neurobiochemical marker of brain damage (neuron-specific enolase [NSE]) with
      respect to degree of disability at the time of admission and neurological
      worsening in acute ischemic stroke patients. We investigated 150 patients with
      cerebrovascular stroke who were admitted within 72 h of onset of stroke in the
      Department of Neurology at SAIMS. Venous blood samples were taken after admission
      and NSE was analyzed by solid enzyme linked immunosorbent assay using Analyzer
      and microplate reader from Biored: Code 680. In all patients, the neurological
      status was evaluated by a standardized neurological examination and the National
      Institutes of Health Stroke Scale on admission and on day 7. Serum NSE
      concentration was found to significantly correlate with both degree of disability
      and neurological worsening in acute ischemic stroke cases in the present study.
      The maximum serum NSE level within 72 h of admission was significantly higher in
      patients with greater degree of disability at the time of admission. Serum NSE
      levels were also found to be significantly elevated in patients with bad
      neurological outcome. Our study showed that serum NSE has high predictive value
      for determining severity and early neurobehavioral outcome after acute stroke.

PMID- 23542315
TI  - Development and characterization of a specific IgG monoclonal antibody toward the
      Lewis x antigen using splenocytes of Schistosoma mansoni-infected mice.
AB  - The parasitic blood fluke Schistosoma mansoni synthesizes immunogenic glycans
      containing the human Lewis x antigen (Le(x); Galactose-beta1-4(Fucalpha1-3)N
      acetylglucosamine-beta-R, also called CD15), but the biological role(s) of this
      antigen in the parasites and in humans is poorly understood. To develop IgG-based
      monoclonal antibodies (mAbs) specific for Le(x), we harvested splenocytes from S.
      mansoni-infected Swiss Webster mice at Week 10 postinfection, when peak IgG
      responses to glycan antigens occur, and generated a panel of hybridomas secreting
      anti-glycan IgG that recognize periodate-sensitive epitopes in soluble egg
      antigens of the parasites, and also recognizes a neoglycoprotein containing a
      pentasaccharide with the Le(x) sequence. One murine mAb, an IgG3 designated
      F8A1.1, bound to glycoproteins and glycolipids from schistosome adults and human
      promyelocytic leukemic HL-60 cells that express Le(x) antigens, as assessed by a
      wide variety of approaches including immunofluorescence staining, confocal
      microscopy, flow cytometry and western blotting, as well as overlay assays of
      glycolipids after thin-layer chromatography. In contrast, F8A1.1 bound weakly to
      cercariae, 3-h schistosomula and human Jurkat cells. We also directly compared
      the glycan specificity of F8A1.1 with commercially available anti-CD15 IgG1
      (clone W6D3) using a defined glycan microarray. The results demonstrated that
      F8A1.1 recognized glycans expressing Le(x) epitopes in a terminal nonreducing
      position, whereas anti-CD15 bound to glycans with multiple repeats of Le(x)
      epitopes, but not to glycans with a single, terminal Le(x) epitope. Our results
      show that F8A1.1 recognizes terminal Le(x) epitopes and can be used for
      identification, immunolocalization, immunoprecipitation and purification of Le(x)
      containing glycoconjugates from schistosomes and mammalian cells.

PMID- 23542316
TI  - Th17 cells and IL-17 are involved in the disruption of vulnerable plaques
      triggered by short-term combination stimulation in apolipoprotein E-knockout
      mice.
AB  - Considerable evidence indicates that type 1 T helper (Th1)- and Th17-mediated
      immune responses promote the formation of atherosclerotic plaques while that
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have a protective effect.
      However, the functions of diverse CD4(+) lymphocyte subsets in plaque rupture
      remain poorly understood because of a shortage of satisfactory plaque rupture
      models. Here, we established a murine model of atherosclerotic plaque rupture
      using a high-fat diet and collar placement on the carotid artery, and triggered
      plaque rupture by short-term stimulation with a combination of
      lipopolysaccharide, phenylephrine injection and cold in apolipoprotein E-knockout
      (ApoE(-/-)) mice. We investigated the associations between Th1 cells, Th17 cells
      and Tregs and plaque rupture by PCR, flow cytometry, ELISA and
      immunohistochemistry. In total, 75% (18/24) of vulnerable plaques, but no stable
      plaques, showed rupture characteristics. The proportion of Th17 cells was
      increased among splenocytes after treatment, but the changes in the levels of Th1
      cells and Tregs were not related to rupture. Furthermore, the treatment resulted
      in high levels of interleukin-17 (IL-17) in the serum and in the region of plaque
      rupture. In vitro, IL-17 increased the level of apoptosis, a major factor
      associated with plaque rupture, in cultured murine vascular smooth muscle cells.
      Th17 cells and IL-17 may be involved in the disruption of vulnerable plaques
      triggered by short-term stimulation with lipopolysaccharide, phenylephrine
      injection and cold in ApoE(-/-)mice. 

PMID- 23542318
TI  - Enhanced biotransformation of nitrobenzene by the synergies of Shewanella species
      and mediator-functionalized polyurethane foam.
AB  - The performance and mechanism of anaerobic treatment of nitrobenzene using the
      combination of Shewanella species and anthraquinone-2-sulfonate-modified
      polyurethane foam (Shewanella/AQS-PUF) were investigated. The results showed that
      Shewanella/AQS-PUF significantly accelerated nitrobenzene bio-reduction (95.6%)
      and aniline formation (94.3%) with nitrobenzene removal rate up to 0.13 mM h(-1).
      Moreover, there were synergistic effects between Shewanella species and AQS-PUF
      on promoting nitrobenzene biotransformation with 5-fold increase in first-order
      rate constant compared to that without AQS-PUF. During this process, AQS-PUF
      could induce Shewanella species to secrete more flavins (0.335 MUM) as redox
      mediator for nitrobenzene bio-reduction. Meanwhile, it was also found that the
      bound EPS of Shewanella species could act as biocatalyst for nitrobenzene
      reduction and the addition of flavins enhanced its catalytic activity. This
      indicated that the EPS of Shewanella species was not only involved in direct bio
      reduction of nitrobenzene, but also interacted with secreted flavins to mediate
      nitrobenzene bio-reduction.

PMID- 23542319
TI  - Metals and polybrominated diphenyl ethers leaching from electronic waste in
      simulated landfills.
AB  - Landfills established prior to the recognition of potential impacts from the
      leaching of heavy metals and toxic organic compounds often lack appropriate
      barriers and pose significant risks of contamination of groundwater. In this
      study, bioavailable metal(oids) and polybrominated diphenyl ethers (PBDEs) in
      leachates from landfill columns that contained intact or broken e-waste were
      studied under conditions that simulate landfills in terms of waste components and
      methods of disposal of e-wastes, and with realistic rainfall. Fourteen elements
      and PBDEs were analysed in leachates over a period of 21 months. The results
      demonstrate that the average concentrations of Al, Ba, Be, Cd, Co, Cr, Cu, Ni,
      Pb, Sb and V in leachates from the column that contained broken e-waste items
      were significantly higher than the column without e-waste. BDE-153 was the
      highest average PBDEs congener in all columns but the average of ?PBDEs levels in
      columns that contained intact e-waste were (3.7 ng/l) and were not significantly
      higher than that in the leachates from the control column.

PMID- 23542320
TI  - Pretreatment of landfill leachate using deep shaft aeration bioreactor (DSAB) in
      cold winter season.
AB  - A pilot-scale deep shaft aeration bioreactor (DSAB) with 110 m in depth and 0.5m
      in diameter for the pretreatment of landfill leachate in winter was operated at a
      daily treatment scale of around 10-20 tons. It was found that the performance of
      the DSAB mainly depended on the inflow loads and concentrations of pollutants.
      NH3-N, TN, COD, TOC removals of 66-94%, 41-64%, 67-87%, 55-92% at organic load
      rate of 1.7-9.4 g CODL(-1)day(-1) and hydraulic retention time of 1-2d were
      obtained using DSAB, respectively, with the lowest ambient temperature of -3 
      degrees C. The effluent COD can be reduced to below 1000 mg/L, an acceptable
      level for advanced treatment using reverse osmosis system, when the influent COD
      was below 7000 mg/L at 10t/d. The EEM and GPC analysis implied that the non
      biodegradable contaminants such as humic- and fulvic-like DOM dominated in the
      organic fractions of the effluent, which rendered the biological treatment
      ineffective. Compared with 20-40% removals obtained using traditional biological
      processes below 15  degrees C, DSAB showed a higher treatment efficiency for COD
      and NH3-N, even though at adverse conditions of poor carbon source, lower C/N
      ratio and high nitrite concentrations in the leachate of test.

PMID- 23542321
TI  - Singlet oxygen mediated apoptosis by anthrone involving lysosomes and
      mitochondria at ambient UV exposure.
AB  - Anthrone a tricyclic aromatic hydrocarbon which is toxic environmental pollutant
      comes in the environment through photooxidation of anthracene. We have studied
      the photomodification of anthrone under environmental conditions. Anthrone
      generates reactive oxygen species (ROS) like (1)O2 through Type-II photodynamic
      reaction. Significant intracellular ROS generation was measured through
      dichlorohydrofluorescein fluorescence intensity. The generation of (1)O2 was
      further substantiated by using specific quencher like sodium azide. UV induced
      photodegradation of 2-deoxyguanosine and photoperoxidation of linoleic acid
      accorded the involvement of (1)O2 in the manifestation of anthrone phototoxicity.
      Phototoxicity of anthrone was done on human keratinocytes (HaCaT) through 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake
      assays. Anthrone induced cell cycle arrest (G2/M-phase) and DNA damage in a
      concentration dependent manner. We found apoptosis as a pattern of cell death
      which was confirmed through sub-G1 fraction, morphological changes, caspase-3
      activation, acridine orange/ethidium bromide staining and phosphatidylserine
      translocation. Mitochondrial depolarization and lysosomal destabilization was
      parallel to apoptotic process. Our RT-PCR results strongly supports our view
      point of apoptotic cell death through up-regulation of pro-apoptotic genes p21
      and Bax, and down regulation of anti-apoptotic gene Bcl2. Therefore, much
      attention should be paid to concomitant exposure of anthrone and UV-R for its
      total environmental impact.

PMID- 23542322
TI  - Organic xenobiotics removal in constructed wetlands, with emphasis on the
      importance of the support matrix.
AB  - Constructed wetlands (CWs) are increasingly popular as an efficient and
      economical alternative to conventional wastewater treatment processes for
      removal, among other pollutants, of organic xenobiotics. In CWs, pollutants are
      removed through the concerted action of their components, whose contribution can
      be maximized by careful selection of those components. Specifically for non
      biodegradable organic pollutants, the materials used as support matrix of CWs can
      play a major role through sorption phenomena. In this review the role played by
      such materials in CWs is examined with special focus on the amount of research
      that has been conducted to date on their sorption properties relatively to
      organic compounds. Where available, the reports on the utilization of some of
      those materials on pilot or full-scale CWs are also recognized. Greatest interest
      has been directed to cheaper and widely available materials. Among these, clays
      are generally regarded as efficient sorbents, but materials originated from
      agricultural wastes have also gained recent popularity. Most available studies
      are lab-scale batch sorption experiments, whereas assays performed in full-scale
      CWs are still scarce. However, the available lab-scale data points to an
      interesting potential of many of these materials for experimentation as support
      matrix of CWs targeted for organic xenobiotics removal.

PMID- 23542323
TI  - Evaluation on the generative mechanism and biological toxicity of microcystin-LR
      disinfection by-products formed by chlorination.
AB  - To control the environmental risk of microcystin-LR disinfection by-products
      (MCLR-DBPs), we evaluated their generative mechanisms and biological toxicity by
      mass spectrometry technology and protein phosphatase inhibition assay. Subject to
      chlorination, MCLR was totally transformed within 45 min and generated 5 types of
      MCLR-DBPs with the chemical formulas of C34H54N10O12, C49H76N10O14Cl2,
      C49H77N10O15Cl, C49H75N10O13Cl, and C49H76N10O14. Isomers for each MCLR-DBP type
      were identified and separated (products 1-9), indicating that the conjugated
      diene in Adda residue was a major target site of disinfection. Though, subsequent
      toxicity test showed the toxicity of MCLR-DBPs on protein phosphatase 1 decreased
      with the extending of disinfection by and large, these DBPs still possessed
      certain biological toxicity (especially for product 5). Combined with
      quantitative analysis, we thought the secondary pollution of MCLR-DBPs in
      drinking water also deserved further attention. This study offers valid technique
      support for MCLR-DBPs identification, contributes to a comprehensive cognition on
      their hazard, and thus has great significance to prevent and control the
      environmental risk induced by microcystins and their DBPs.

PMID- 23542324
TI  - Application of skin contamination studies of ammonia gas for management of
      hazardous material incidents.
AB  - In an atmospheric HAZMAT release unprotected public dermal exposure is often of
      short duration, but with potential secondary exposure if not decontaminated
      promptly. Mass decontamination is resource intensive and needs to be justified.
      For many HAZMAT agents there is no evidence-base on which to provide guidance on
      decontamination, particularly for non-symptomatic worried well. It is important
      to understand the influence of street clothing and environmental and other
      factors. Ammonia is a common HAZMAT agent and was selected for in vitro human
      skin studies of absorption, penetration and off-gassing at test concentrations up
      to 2000 ppm, incorporating primary and secondary exposure combinations up to 60
      min. Intact skin provided a good barrier to ammonia penetration. Heavy street
      clothing such as denim was found to act as an initial barrier to skin absorption
      but subsequently as a reservoir for secondary exposure, under variable
      temperature and humidity conditions. Rapid off-gassing was observed for lighter
      fabrics including polyester and cotton. The findings here have been summarized as
      a set of practical guidelines for emergency responders who are required to make
      decisions about ammonia decontamination including for non-symptomatic
      individuals. This evidence-based diagrammatic approach allows for specific
      actions based on different atmospheric ammonia concentrations and other
      parameters.

PMID- 23542325
TI  - Survival of GFP-tagged Rhodococcus sp. D310-1 in chlorimuron-ethyl-contaminated
      soil and its effects on the indigenous microbial community.
AB  - The recently isolated bacterial strain Rhodococcus sp. D310-1 can degrade high
      concentrations of chlorimuron-ethyl (up to 1000 mg L(-1)), indicating its
      potential for the bioremediation of soil contaminated with high levels of
      chlorimuron-ethyl. In this study, Rhodococcus sp. D310-1 was tagged with green
      fluorescent protein gene (gfp) to track its survival in soil. Subsequently,
      degradation activity of the gfp-tagged strain and its effects on indigenous
      microbial community were analyzed. Results showed the cell numbers of Rhodococcus
      sp. D310-1::gfp in non-sterilized soil maintained at 8.5 * 10(4) cells g(-1) dry
      soil 45 days after inoculation of 7.74 * 10(6) cells g(-1) dry soil and
      approximately 49% of chlorimuron-ethyl was removed. However, The cell numbers of
      Rhodococcus sp. D310-1::gfp in sterilized samples increased gradually to 7.85 *
      10(7) cells g(-1) dry soil and approximately 78% of chlorimuron-ethyl was
      removed. PCR-DGGE demonstrated that inoculation of this gfp-tagged strain in
      chlorimuron-ethyl-contaminated soil has negligible impact on the community
      structure of bacteria, actinomycetes and fungi. These results indicate that
      Rhodococcus sp. D310-1 is effective for the remediation of chlorimuron-ethyl
      contaminated soil and also provides valuable information about the behavior of
      the inoculant population during bioremediation, which could be directly used in
      the risk assessment of inoculant population and optimization of bioremediation
      process.

PMID- 23542327
TI  - Where is the citizen? Comparing civic spaces in long-term mental healthcare.
AB  - This paper explores the spatial properties of several notions of citizenship used
      in long-term mental healthcare. We claim that speaking of citizenship is a way of
      drawing borders: some people fall inside and some fall outside the civic domain.
      Informed by Science and Technology Studies, we use topological methods to see
      where borders are drawn by different notions of citizenship and analyse the
      notions of space that are co-produced with them. With this study we develop a new
      way of thinking about citizenship: citizenship as 'being-in-place'. Being in
      place can emancipate clients and help them expand their social networks.

PMID- 23542326
TI  - Chitosan-cellulose composite materials: preparation, characterization and
      application for removal of microcystin.
AB  - We developed a simple and one-step method to prepare biocompatible composites
      from cellulose (CEL) and chitosan (CS). [BMIm(+)Cl(-)], an ionic liquid (IL), was
      used as a green solvent to dissolve and prepare the [CEL+CS] composites. Since
      majority (>88%) of IL used was recovered for reuse by distilling the aqueous
      washings of [CEL+CS], the method is recyclable. XRD, FTIR, NIR, (13)C CP-MAS-NMR
      and SEM were used to monitor the dissolution and to characterize the composites.
      The composite was found to have combined advantages of their components: superior
      mechanical strength (from CEL) and excellent adsorption capability for
      microcystin-LR, a deadly toxin produced by cyanobacteria (from CS). Specifically,
      the mechanical strength of the composites increased with CEL loading; e.g., up to
      5* increase in tensile strength was achieved by adding 80% of CEL into CS.
      Kinetic results of adsorption confirm that unique properties of CS remain intact
      in the composite, i.e., it is not only a very good adsorbent for microcystin but
      also is better than all other available adsorbents. For example, it can adsorb 4*
      times more microcystin than the best reported adsorbent. Importantly, the
      microcystin adsorbed can be quantitatively desorbed to enable the composite to be
      reused with similar adsorption efficiency.

PMID- 23542328
TI  - "It is just not part of the culture here": young adults' photo-narratives about
      smoking, quitting, and healthy lifestyles in Vancouver, Canada.
AB  - In this article we consider young adults' photo-narratives about smoking and
      quitting and their linkages to themes of healthy lifestyles and the culture of
      place in Vancouver, Canada. Drawing from a pilot study using participant-driven
      photography with a group of twelve young women and men ages nineteen to twenty
      six, participants' visual and narrative representations of being a smoker and the
      process of quitting smoking were analyzed. Findings suggest "healthy lifestyle"
      imperatives within the Vancouver context may be productive for facilitating
      cessation, but may also have exclusionary effects.

PMID- 23542329
TI  - Coordinating care in patients with cirrhosis.

PMID- 23542330
TI  - Health benefits and cost-effectiveness of a hybrid screening strategy for
      colorectal cancer.
AB  - BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines recommend
      screening schedules for each single type of test except for concurrent
      sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost
      effectiveness of a hybrid screening strategy that was based on a fecal
      immunological test (FIT) and colonoscopy. METHODS: We conducted a cost
      effectiveness analysis by using the Archimedes Model to evaluate the effects of
      different CRC screening strategies on health outcomes and costs related to CRC in
      a population that represents members of Kaiser Permanente Northern California.
      The Archimedes Model is a large-scale simulation of human physiology, diseases,
      interventions, and health care systems. The CRC submodel in the Archimedes Model
      was derived from public databases, published epidemiologic studies, and clinical
      trials. RESULTS: A hybrid screening strategy led to substantial reductions in CRC
      incidence and mortality, gains in quality-adjusted life years (QALYs), and
      reductions in costs, comparable with those of the best single-test strategies.
      Screening by annual FIT of patients 50-65 years old and then a single colonoscopy
      when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained
      110 QALYs for every 1000 people during a period of 30 years, compared with no
      screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons
      at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared
      with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an
      incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over
      the ranges of parameters examined, the cost-effectiveness of hybrid screening
      strategies was slightly more sensitive to the adherence rate with colonoscopy
      than the adherence rate with yearly FIT. Uncertainties associated with estimates
      of FIT performance within a program setting and sensitivities for flat and right
      sided lesions are expected to have significant impacts on the cost-effectiveness
      results. CONCLUSIONS: In our simulation model, a strategy of annual or biennial
      FIT, beginning when patients are 50 years old, with a single colonoscopy when
      they are 66 years old, delivers clinical and economic outcomes similar to those
      of CRC screening by single-modality strategies, with a favorable impact on
      resources demand.

PMID- 23542331
TI  - Efficacy and safety of oral chelators in treatment of patients with Wilson
      disease.
AB  - BACKGROUND & AIMS: Wilson disease is a genetic copper storage disorder that
      causes hepatic and neurologic symptoms. Chelating agents (D-penicillamine,
      trientine) are used as first-line therapies for symptomatic patients, but there
      are few data from large cohorts. We assessed the safety of D-penicillamine and
      trientine therapy and outcomes of patients with Wilson disease. METHODS: We
      performed a retrospective analysis of data on 380 patients with Wilson disease
      from tertiary care centers in Germany and Austria, and 25 additional patients
      from the EUROWILSON registry. Chelator-based treatment regimens were analyzed for
      their effect on neurologic and hepatic symptoms and for adverse events that led
      to discontinuation of therapy (Kaplan-Meier estimation; data were collected for a
      mean of 13.3 y after therapy began). RESULTS: Changes in medication were common,
      resulting in analysis of 471 chelator monotherapies (326 patients receiving D
      penicillamine and 141 receiving trientine). Nine of 326 patients treated with D
      penicillamine and 3 of 141 patients given trientine underwent liver
      transplantation. Adverse events leading to discontinuation of treatment were more
      frequent among those receiving D-penicillamine than trientine (P = .039). Forty
      eight months after therapy, hepatic deterioration was reported in only 4 of 333
      patients treated initially with a chelating agent. Hepatic improvements were
      observed in more than 90%, and neurologic improvements were observed in more than
      55%, of therapy-naive patients, and values did not differ significantly between
      treatments. However, neurologic deterioration was observed less frequently in
      patients given D-penicillamine first (6 of 295) than those given trientine first
      (4 of 38; P = .018). CONCLUSIONS: Chelating agents are effective therapies for
      most patients with Wilson disease; D-penicillamine and trientine produce
      comparable outcomes, although D-penicillamine had a higher rate of adverse
      events. Few patients receiving chelation therapy had neurologic deterioration,
      which occurred more frequently in patients who received trientine.

PMID- 23542332
TI  - Diagnosis and management of Clostridium difficile infection.
AB  - Clostridium difficile infection (CDI) is increasing in frequency and severity in
      and out of the hospital, with a high probability of recurrence after treatment.
      The recent literature on CDI was reviewed using PubMed to include recent
      publications dealing with diagnosis and therapy. Real-time polymerase chain
      reaction is a sensitive and useful diagnostic test for CDI but there are growing
      concerns of false-positive test results if the rate of CDI is low in the patient
      population providing samples and/or if the population being studied commonly
      includes people with C difficile colonization. Recommended therapy of CDI
      includes oral metronidazole for milder cases of CDI and oral vancomycin or
      fidaxomicin for more severe cases, each given for 10 days. Colectomy is being
      performed more frequently in patients with fulminant CDI. For treatment of first
      recurrences the drug used in the first bout can be used again and for second
      recurrences longer courses of vancomycin often are given in a tapered dose or
      intermittently to allow gut flora reconstitution, or other treatments including
      fidaxomicin may be used. Bacteriotherapy with fecal transplantation is playing an
      increasing role in therapy of recurrent cases. Metagenomic studies of patients
      with CDI during successful therapy are needed to determine how best to protect
      the flora from assaults from antibacterial drugs and to develop optimal
      therapeutic approaches. Immunotherapy and immunoprophylaxis offer opportunities
      to prevent CDI, to speed up recovery from CDI, and to eliminate recurrent
      infection. Humanized monoclonal antitoxin antibodies and active immunization with
      vaccines against C difficile or its toxins are both in development and appear to
      be of potential value. 

PMID- 23542333
TI  - Debilitating bone pain in a patient with celiac disease.

PMID- 23542334
TI  - Muscle cramps in liver disease.
AB  - Muscle cramps are common in patients with liver disease and adversely influence
      quality of life. The exact mechanisms by which they occur remain unclear,
      although a number of pathophysiological events unique to liver disease may
      contribute. Clinical studies have identified alterations in 3 areas: nerve
      function, energy metabolism, and plasma volume/electrolytes. Treatments have
      focused on these particular areas with varied results. This review will focus on
      the clinical features of muscle cramps in patients with liver disease and review
      potential mechanisms and current therapies. 

PMID- 23542335
TI  - Characterization of the ovine complement 4 binding protein-beta (C4BPB) chain as
      a serum biomarker for enhanced diagnosis of sheep scab.
AB  - Sheep scab, caused by the highly contagious mite Psoroptes ovis, is endemic in a
      number of sheep-producing countries worldwide, and is a major animal welfare and
      economic concern. Recent developments in the diagnosis of sheep scab include a
      highly sensitive and specific serum antibody-based assay which can be used to
      indicate exposure to the parasite but not necessarily current disease status.
      Here, a transcriptomic and bioinformatics analysis of the circulating leukocytes
      of sheep with active P. ovis infestation indicated that the transcription levels
      of complement 4 binding protein beta (C4BPB) increased by 12 fold from pre
      infestation to 6 weeks post-infestation. Semi-quantitative studies confirmed
      increased serum C4BPB protein levels in sheep infested with P. ovis. To quantify
      this serum protein response and characterize ovine C4BPB as a biomarker for
      active P. ovis infestation, the ovine C4BPB gene was sequenced, a recombinant
      protein expressed, antibodies against this protein were raised in rabbits and a
      sandwich ELISA developed. The results from this assay indicated that serum C4BPB
      protein levels increased 4-fold from pre-infestation to 6 weeks post-infestation,
      which demonstrated the potential of the assay to quantify C4BPB in sheep sera and
      indicated the potential of C4BPB as a biomarker of current disease status in
      sheep post-infestation and post-treatment.

PMID- 23542336
TI  - Menstrual cycle and reproductive aging alters immune reactivity, NGF expression,
      antioxidant enzyme activities, and intracellular signaling pathways in the
      peripheral blood mononuclear cells of healthy women.
AB  - Reproductive senescence in women is a process that begins with regular menstrual
      cycles and culminates in menopause followed by gradual development of diseases
      such as autoimmune diseases, osteoporosis, neurodegenerative diseases, and
      hormone-dependent cancers. The age-associated impairment in the functions of
      neuroendocrine system and immune system results in menopause which contributes to
      subsequent development of diseases and cancer. The aim of this study is to
      characterize the alterations in immune responses, compensatory factors such as
      nerve growth factor (NGF) and antioxidant enzyme activities, and the molecular
      mechanisms of actions in the peripheral blood mononuclear cells (PBMCs) of young
      (follicular and luteal phases), middle-aged, and old healthy women. Peripheral
      blood mononuclear cells were isolated from young women in follicular and luteal
      phases of the menstrual cycle (n=20; 22.6+/-2.9 yrs), middle-aged women (n=19;
      47.1+/-3.8 yrs; perimenopausal) and old (n=16; 63.2+/-4.7 yrs; post-menopausal)
      women and analyzed for Concanavalin (Con A)-induced proliferation of lymphocytes
      and cytokine (IL-2 and IFN-gamma) production, expression of NGF, p-NF-kappaB, p
      ERK, p-CREB, and p-Akt, antioxidant enzymes [superoxide dismutase (SOD),
      catalase, and glutathione peroxidase (GPx), glutathione-S-transferase (GST)],
      extent of lipid peroxidation, and nitric oxide (NO) production. Serum gonadal
      hormones (17beta-estradiol and progesterone) were also measured. A characteristic
      age- and menstrual cycle-related change was observed in the serum gonadal hormone
      secretion (estrogen and progesterone), T lymphocyte proliferation and IFN-gamma
      production. Salient features include the age-related decline observed in target
      derived growth factors (lymphocyte NGF expression), signaling molecules (p
      ERK/ERK and p-CREB/CREB ratios) and compensatory factors such as the activities
      of plasma and PBMC antioxidant enzymes (SOD and catalase) and NO production.
      Further, an age-associated increase in p-NF-kappaB expression and lipid
      peroxidation was observed. Also, serum 17beta-estradiol levels were positively
      correlated with IFN-gamma production, SOD activity and NGF expression in the
      PBMCs. These results suggest that alterations in the levels of gonadal hormones
      are associated with immunosenescence characterized by decreased IFN-gamma
      production and proliferation of T lymphocytes, decline in NGF expression, SOD and
      catalase activities, NO production, and signaling mechanisms and thus, may
      increase the incidence of diseases and cancer in women.

PMID- 23542337
TI  - Accuracy of gas exchange monitoring during noninvasive ventilation: an in vitro
      metabolic simulation.
AB  - BACKGROUND: Gas exchange monitoring by indirect calorimetry (IC) during
      noninvasive ventilation (NIV) is desirable but currently not available. Leaks
      around the mask preclude reliable measurements of carbon dioxide production
      (VCO2) and oxygen consumption (VO2) in this population. We aimed to examine the
      impact of system leaks and gas flows on the accuracy of gas exchange measurements
      during NIV using an in vitro metabolic simulation. MATERIALS AND METHODS: We
      examined the agreement between VCO2 and VO2 measurements by IC (using a novel
      canopy device) and reference values generated during an in vitro metabolic
      simulation of NIV at room air. The flow rate of gas sampled by the IC device
      (VIC) was set relative to the output flow of the ventilator (VVENT) to obtain a
      range of sample factors (SF = VIC/VVENT). Linear regression was used to determine
      the effect of SF on the accuracy of the system. RESULTS: An acceptable agreement
      between measured and reference values was observed, with mean bias (limits of
      agreement) of -3.3% (-6.9% to 0.3%) and -10.6% (-14.9% to -6.4%) for VCO2 and
      VO2, respectively. An SF of 1.25 was associated with the highest accuracy of
      measurement. VO2 measurement accuracy deteriorated with system leak and at SF
      >1.25 and was linearly related to sample dilution by ambient air entrainment.
      CONCLUSIONS: A novel canopy device with titration of IC sample flow in relation
      to the ventilator flow allowed in vitro gas exchange measurements during
      simulated NIV with acceptable accuracy. This model needs to be tested in clinical
      settings.

PMID- 23542338
TI  - A genomewide association study of smoking relapse in four European population
      based samples.
AB  - OBJECTIVES: Genomewide association studies (GWAS) have identified clear evidence
      of genetic markers for nicotine dependence. Other smoking phenotypes have been
      tested, but the results are less consistent. The tendency to relapse versus the
      ability to maintain long-term abstinence has received little attention in genetic
      studies; thus, our aim was to provide a better biological understanding of this
      phenotype through the identification of genetic loci associated with smoking
      relapse. METHODS: We carried out a GWAS on data from two European population
      based collections, including a total of 835 cases (relapsers) and 990 controls
      (abstainers). Top-ranked findings from the discovery phase were tested for
      replication in two additional independent European population-based cohorts.
      RESULTS: Of the seven top markers from the discovery phase, none were
      consistently associated with smoking relapse across all samples and none reached
      genomewide significance. A single-nucleotide polymorphism rs1008509, within the
      Xylosyltransferase II (XYLT2) gene, was suggestively associated with smoking
      relapse in the discovery phase (beta=-0.504; P=5.6E-06) and in the first
      replication sample (ALSPAC) (beta=-0.27; P=0.004; n=1932), but not in the second
      sample (KORA) (beta=0.19; P=0.138; n=912). We failed to identify an association
      between loci implicated previously in other smoking phenotypes and smoking
      relapse. CONCLUSION: Although no genomewide significant findings emerged from
      this study, we found that loci implicated in other smoking phenotypes were not
      associated with smoking relapse, which suggests that the neurobiology of smoking
      relapse and long-term abstinence may be distinct from biological mechanisms
      implicated in the development of nicotine dependence.

PMID- 23542339
TI  - Cargo recognition explains nuclear transport regulation induced by nuclear pore
      complex reorganization.

PMID- 23542340
TI  - One platform, five brands: how nature cuts the cost on riboswitches.

PMID- 23542341
TI  - What makes a protein fold amenable to functional innovation? Fold polarity and
      stability trade-offs.
AB  - Protein evolvability includes two elements--robustness (or neutrality, mutations
      having no effect) and innovability (mutations readily inducing new functions).
      How are these two conflicting demands bridged? Does the ability to bridge them
      relate to the observation that certain folds, such as TIM barrels, accommodate
      numerous functions, whereas other folds support only one? Here, we hypothesize
      that the key to innovability is polarity--an active site composed of flexible,
      loosely packed loops alongside a well-separated, highly ordered scaffold. We show
      that highly stabilized variants of TEM-1 beta-lactamase exhibit selective
      rigidification of the enzyme's scaffold while the active-site loops maintained
      their conformational plasticity. Polarity therefore results in stabilizing,
      compensatory mutations not trading off, but instead promoting the acquisition of
      new activities. Indeed, computational analysis indicates that in folds that
      accommodate only one function throughout evolution, for example, dihydrofolate
      reductase, >= 60% of the active-site residues belong to the scaffold. In
      contrast, folds associated with multiple functions such as the TIM barrel show
      high scaffold-active-site polarity (~20% of the active site comprises scaffold
      residues) and >2-fold higher rates of sequence divergence at active-site
      positions. Our work suggests structural measures of fold polarity that appear to
      be correlated with innovability, thereby providing new insights regarding protein
      evolution, design, and engineering.

PMID- 23542342
TI  - Role of motif B loop in allosteric regulation of RNA-dependent RNA polymerization
      activity.
AB  - Increasing amounts of data show that conformational dynamics are essential for
      protein function. Unveiling the mechanisms by which this flexibility affects the
      activity of a given enzyme and how it is controlled by other effectors opens the
      door to the design of a new generation of highly specific drugs. Viral RNA
      dependent RNA polymerases (RdRPs) are not an exception. These enzymes, essential
      for the multiplication of all RNA viruses, catalyze the formation of
      phosphodiester bonds between ribonucleotides in an RNA-template-dependent
      fashion. Inhibition of RdRP activity will prevent genome replication and virus
      multiplication. Thus, RdRPs, like the reverse transcriptase of retroviruses, are
      validated targets for the development of antiviral therapeutics. X-ray
      crystallography of RdRPs trapped in multiple steps throughout the catalytic
      process, together with NMR data and molecular dynamics simulations, have shown
      that all polymerase regions contributing to conserved motifs required for
      substrate binding, catalysis and product release are highly flexible and some of
      them are predicted to display correlated motions. All these dynamic elements can
      be modulated by external effectors, which appear as useful tools for the
      development of effective allosteric inhibitors that block or disturb the
      flexibility of these enzymes, ultimately impeding their function. Among all
      movements observed, motif B, and the B-loop at its N-terminus in particular,
      appears as a new potential druggable site.

PMID- 23542344
TI  - A conserved spiral structure for highly diverged phage tail assembly chaperones.
AB  - Tail assembly chaperones (TACs) are a family of proteins likely required for the
      morphogenesis of all long-tailed phages. In this study, we determined the crystal
      structure of gp13, the TAC of phage HK97. This structure is similar to that of
      the TAC from the Lactococcus phage p2 and two unannotated structures of likely
      TACs encoded in prophage-derived regions of Bacillus subtilis and Bacillus
      stearothermophilus. Despite the high sequence divergence of these proteins, gp13
      forms a ring structure with similar dimensions to the spirals observed in the
      crystal lattices of these other proteins. Remarkably, these similar quaternary
      structures are formed through very different interprotomer interactions. We
      present functional data supporting the biological relevance of these spiral
      structures and propose that spiral formation has been the primary requirement for
      these proteins during evolution. This study presents an unusual example of
      diverged protein sequences and oligomerization mechanisms in the presence of
      conserved quaternary structure. 

PMID- 23542343
TI  - Tail tip proteins related to bacteriophage lambda gpL coordinate an iron-sulfur
      cluster.
AB  - The assembly of long non-contractile phage tails begins with the formation of the
      tail tip complex (TTC). TTCs are multi-functional protein structures that mediate
      host cell adsorption and genome injection. The TTC of phage lambda is assembled
      from multiple copies of eight different proteins, including gpL. Purified
      preparations of gpL and several homologues all displayed a distinct reddish
      color, suggesting the binding of iron by these proteins. Further characterization
      of the gpL homologue from phage N15, which was most amenable to in vitro
      analyses, showed that it contains two domains. The C-terminal domain was
      demonstrated to coordinate an iron-sulfur cluster, providing the first example of
      a viral structural protein binding to this type of metal group. We characterized
      the iron-sulfur cluster using inductively coupled plasma-atomic emission
      spectroscopy, absorbance spectroscopy, and electron paramagnetic resonance
      spectroscopy and found that it is an oxygen-sensitive [4Fe-4S](2+) cluster. Four
      highly conserved cysteine residues were shown to be required for coordinating the
      iron-sulfur cluster, and substitution of any of these Cys residues with Ser or
      Ala within the context of lambda gpL abolished biological activity. These data
      imply that the intact iron-sulfur cluster is required for function. The presence
      of four conserved Cys residues in the C-terminal regions of very diverse gpL
      homologues suggest that utilization of an iron-sulfur cluster is a widespread
      feature of non-contractile tailed phages that infect Gram-negative bacteria. In
      addition, this is the first example of a viral structural protein that binds an
      iron-sulfur cluster. 

PMID- 23542345
TI  - Hepatitis B virus HBx protein impairs liver regeneration through enhanced
      expression of IL-6 in transgenic mice.
AB  - BACKGROUND & AIMS: Conflicting results have been reported regarding the impact of
      hepatitis B virus X protein (HBx) expression on liver regeneration triggered by
      partial hepatectomy (PH). In the present report we investigated the mechanisms by
      which HBx protein alters hepatocyte proliferation after PH. METHODS: PH was
      performed on a transgenic mouse model in which HBx expression is under the
      control of viral regulatory elements and liver regeneration was monitored. LPS,
      IL-6 neutralizing antibody, and SB203580 were injected after PH to evaluate IL-6
      participation during liver regeneration. RESULTS: Cell cycle progression of
      hepatocytes was delayed in HBx transgenic mice compared to WT animals. Moreover,
      HBx induced higher secretion of IL-6 soon after PH. Upregulation of IL-6 was
      associated with an elevation of STAT3 phosphorylation, SOCS3 transcript
      accumulation and a decrease in ERK1/2 phosphorylation in the livers of HBx
      transgenic mice. The involvement of IL-6 overexpression in cell cycle
      deregulation was confirmed by the inhibition of liver regeneration in control
      mice after the upregulation of IL-6 expression using LPS. In addition, IL-6
      neutralization with antibodies was able to restore liver regeneration in HBx
      mice. Finally, the direct role of p38 in IL-6 secretion after PH was demonstrated
      using SB203580, a pharmacological inhibitor. CONCLUSIONS: HBx is able to induce
      delayed hepatocyte proliferation after PH, and HBx-induced IL-6 overexpression is
      involved in delayed liver regeneration. By modulating IL-6 expression during
      liver proliferation induced by stimulation of the cellular microenvironment, HBx
      may participate in cell cycle deregulation and progression of liver disease.

PMID- 23542346
TI  - Telaprevir can be successfully and safely used to treat older patients with
      genotype 1b chronic hepatitis C.
AB  - BACKGROUND & AIMS: This study was performed to evaluate the efficacy of a triple
      therapy in older Japanese patients; telaprevir (TVR) was added to pegylated
      interferon alpha2b and ribavirin. METHODS: This prospective study enrolled 120
      genotype 1b patients with chronic hepatitis C who received 12 weeks of triple
      therapy followed by a 12-week dual therapy that included pegylated interferon
      alpha2b and ribavirin. Patients were categorized according to age: group A, 64
      patients aged >60 and group B, 56 patients aged ?60. Serum HCV RNA levels were
      monitored by COBAS TaqMan HCV test. RESULTS: The rates of undetectable HCV RNA at
      week 4 (rapid virological response, RVR) were 73.4% in group A and 73.2% in group
      B. No significant difference in sustained virological response (SVR) was found
      between groups A (76.6%) and B (83.9%) (p=0.314). The SVR rates for patients with
      interleukin 28B (IL28B) (rs8099917) TT allele (89.4% and 91.9% for groups A and
      B) were significantly higher than for those with the IL28B TG/GG allele (41.2%
      and 68.4%, respectively) (both p<0.05). Multivariate analysis extracted IL28B TT
      and RVR as independent factors associated with SVR. Adverse effects resulted in
      treatment discontinuation by 12.5% in each group. Hemoglobin decrease
      significantly differed between groups A and B: the decrease to <=100 g/L, to 85 -
      <100g/L, and to <85 g/L, was 9.4%, 40.6%, and 50% in group A patients,
      respectively, and 41.1%, 25%, and 33.9% in group B patients, respectively
      (p=0.0006). CONCLUSIONS: TVR-based triple therapy can be successfully used to
      treat older patients with genotype 1b chronic hepatitis C.

PMID- 23542347
TI  - Arylacetamide deacetylase: a novel host factor with important roles in the
      lipolysis of cellular triacylglycerol stores, VLDL assembly and HCV production.
AB  - BACKGROUND & AIMS: Very low density lipoproteins (VLDLs) are triacylglycerol (TG)
      rich lipoproteins produced by the human liver. VLDLs derive the majority of their
      TG cargo from the lipolysis of TG stored in hepatocellular lipid droplets (LDs).
      Important roles for LDs and the VLDL secretory pathway in the cell culture
      production of infectious hepatitis C virus (HCV) have been established. We
      hypothesized that TG lipolysis and VLDL production are impaired during HCV
      infection so that these cellular processes can be diverted towards HCV
      production. METHODS: We used an HCV permissive cell culture system (JFH-1/HuH7.5
      cells) to examine the relationship between TG lipolysis, VLDL assembly, and the
      HCV lifecycle using standard biochemical approaches. RESULTS: Lipolysis of
      cellular TG and VLDL production were impaired in HCV infected cells during the
      early peak of viral infection. This was partially explained by an apparent
      deficiency of a putative TG lipase, arylacetamide deacetylase (AADAC). The re
      introduction of AADAC to infected cells restored cellular TG lipolysis,
      indicating a role for HCV-mediated downregulation of AADAC in this process.
      Defective lipolysis of cellular TG stores and VLDL production were also observed
      in HuH7.5 cells stably expressing a short hairpin RNA targeting AADAC expression,
      proving AADAC deficiency contributes to these defective pathways. Finally,
      impaired production of HCV was observed with AADAC knockdown cells, demonstrating
      a role for AADAC in the HCV lifecycle. CONCLUSIONS: This insight into the biology
      of HCV infection and possibly pathogenesis identifies AADAC as a novel and
      translationally relevant therapeutic target.

PMID- 23542349
TI  - Myopia and glaucoma: diagnostic and therapeutic challenges.
AB  - PURPOSE OF REVIEW: There is strong epidemiologic evidence linking myopia with
      glaucomatous disease, but a myopic optic nerve can pose significant challenges
      with regard to making the correct diagnosis of glaucoma. This review provides an
      overview of these diagnostic and therapeutic challenges with a particular focus
      on how the growing prevalence of myopia among specific populations may impact
      such therapy. RECENT FINDINGS: For a given individual, the link between myopia
      and glaucoma remains murky in many circumstances, largely because of the fact
      that it is difficult to separate out myopia-related structural and functional
      abnormalities from 'true' glaucomatous changes. Using optical coherence
      tomography (OCT) imaging, myopia has been found to be associated with temporal
      displacement and thinning of the superior and inferior nerve fiber layer bundles.
      In particular, sequential generations of 'Asian' ethnicities have been noted to
      demonstrate increasing rates of high myopia at earlier ages, sometimes with
      associated visual field defects at normal intraocular pressures. As is the case
      with any progressive condition, it is often not possible to distinguish
      glaucomatous from nonglaucomatous disease based on a single examination, and thus
      follow-up with OCT or perimetry from an established baseline is useful. SUMMARY:
      Although myopia is a known risk factor for glaucoma, it may also result in
      structural and functional defects that cannot be distinguished from those caused
      by glaucoma based solely on cross-sectional information. Longitudinal observation
      may be necessary to distinguish among the multiple effects of myopia on the optic
      nerve and the natural history of glaucoma, which may vary substantially amongst
      those who are affected.

PMID- 23542348
TI  - Hepatitis C virus NS4B blocks the interaction of STING and TBK1 to evade host
      innate immunity.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) is a major human viral pathogen that
      causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. In most
      cases, acute HCV infection becomes persistent, at least in part due to viral
      evasion of host innate immune response. Although HCV genomic RNA contains
      pathogen-associated molecular pattern (PAMP) that is able to induce host
      interferon responses, HCV can shut down the responses by using the viral NS3/4A
      protease to cleave MAVS/VISA and TRIF, two key adaptor molecules essential for
      the interferon signaling activation. The aim of this study was to explore a novel
      NS3/4A-independent mechanism HCV utilizes to evade host innate immune responses.
      METHODS: We used the interferon promoter-reporter system to screen HCV encoded
      proteins for their activities to suppress the interferon signaling and to
      determine the molecular targets of viral proteins. Co-immunoprecipitation,
      confocal microscopy, and siRNA-based gene silencing were used to investigate the
      molecular mechanism. RESULTS: We found that, in addition to NS3/4A, NS4B can
      suppress double-stranded RNA or RNA virus induced interferon activation. NS4B
      interacts with STING/MITA, an important molecule that mediates the HCV PAMP
      induced interferon signaling. Mechanistic studies indicated that NS4B disrupts
      the interactions between STING/MITA and TBK1. CONCLUSIONS: In conclusion, we
      reported an additional mechanism for HCV evasion of host interferon responses in
      which viral NS4B protein targets STING/MITA to suppress the interferon signaling.
      Our results present important evidence for the control of interferon response by
      HCV, and shed more light on the molecular mechanisms underlying the persistence
      of HCV infection.

PMID- 23542351
TI  - Current world literature. Glaucoma.

PMID- 23542350
TI  - Glaucoma therapy and ocular surface disease: current literature and
      recommendations.
AB  - PURPOSE OF REVIEW: To provide an update on clinical and experimental literature
      for ocular surface effects of glaucoma therapy and to provide practical
      guidelines for ophthalmologists treating glaucoma patients with ocular surface
      disease (OSD). RECENT FINDINGS: Preservatives, notably benzalkonium chloride
      (BAK), continue to contribute to OSD and demonstrate a variety of toxic ocular
      effects both in-vitro, and in animal/human studies. Recent literature frequently
      compares BAK with Polyquad, SofZia, and preservative-free therapies. Some
      clinical benefit has been demonstrated with newer BAK-free alternatives. SUMMARY:
      BAK-free and preservative-free therapies are becoming available but are not
      always a feasible alternative. It is important to recognize different clinical
      manifestations of allergy and chronic inflammation and to discuss options for
      patients experiencing OSD.

PMID- 23542353
TI  - Proteomics analysis suggests broad functional changes in potato leaves triggered
      by phosphites and a complex indirect mode of action against Phytophthora
      infestans.
AB  - Phosphite (salts of phosphorous acid; Phi)-based fungicides are increasingly used
      in controlling oomycete pathogens, such as the late blight agent Phytophthora
      infestans. In plants, low amounts of Phi induce pathogen resistance through an
      indirect mode of action. We used iTRAQ-based quantitative proteomics to
      investigate the effects of phosphite on potato plants before and after infection
      with P. infestans. Ninety-three (62 up-regulated and 31 down-regulated)
      differentially regulated proteins, from a total of 1172 reproducibly identified
      proteins, were identified in the leaf proteome of Phi-treated potato plants. Four
      days post-inoculation with P. infestans, 16 of the 31 down-regulated proteins
      remained down-regulated and 42 of the 62 up-regulated proteins remained up
      regulated, including 90% of the defense proteins. This group includes
      pathogenesis-related, stress-responsive, and detoxification-related proteins.
      Callose deposition and ultrastructural analyses of leaf tissues after infection
      were used to complement the proteomics approach. This study represents the first
      comprehensive proteomics analysis of the indirect mode of action of Phi,
      demonstrating broad effects on plant defense and plant metabolism. The proteomics
      data and the microscopy study suggest that Phi triggers a hypersensitive response
      that is responsible for induced resistance of potato leaves against P. infestans.
      BIOLOGICAL SIGNIFICANCE: Phosphie triggers complex functional changes in potato
      leaves that are responsible for the induced resistance against Phytophthora
      infestans. This article is part of a Special Issue entitled: Translational Plant
      Proteomics.

PMID- 23542354
TI  - A systematic quantitative proteomic examination of multidrug resistance in
      Acinetobacter baumannii.
AB  - Multidrug-resistant Acinetobacter baumannii strains have been examined at the DNA
      sequence level, but seldom using large-scale quantitative proteomics. We have
      compared the proteome of the multidrug resistant strain BAA-1605, with the
      proteome of the drug-sensitive strain ATCC 17978, using iTRAQ labeling and online
      2D LC/MS/MS for peptide/protein identification. Of 1484 proteins present in at
      least 2 of 4 independent experiments, 114 are 2-fold to 66-fold more abundant in
      BAA-1605, and 99 are 2-fold to 50-fold less abundant. Proteins with 2-fold or
      greater abundance in the multidrug resistant strain include drug-, antibiotic-,
      and heavy metal-resistance proteins, stress-related proteins, porins, membrane
      transporters, proteins important for acquisition of foreign DNA, biofilm-related
      proteins, cell-wall and exopolysaccharide-related proteins, lipoproteins,
      metabolic proteins, and many with no annotated function. The porin CarO,
      inactivated in carbapenem-resistant strains, is 2.3-fold more abundant in BAA
      1605. Likewise, the porin OmpW, less abundant in carbapenem- and colistin
      resistant A. baumannii strains, is 3-fold more abundant in BAA-1605. Nine
      proteins, all present in the drug-sensitive strain but from 2.2-fold to 16-fold
      more abundant in the MDR strain, can potentially account for the observed
      resistance of BAA-1605 to 18 antibiotics. BIOLOGICAL SIGNIFICANCE: Multidrug
      resistant (MDR) strains of the pathogen Acinetobacter baumannii are a significant
      cause of hospital-acquired infections, are associated with increased mortality
      and length of stay, and may be a major factor underlying the spread of this
      pathogen, which is difficult to eradicate from clinical settings. To obtain a
      better understanding of antimicrobial resistance mechanisms in MDR A. baumannii,
      we report the first large scale 2D LC/MS/MS-based quantitative proteomics
      comparison of a drug-sensitive strain and an MDR strain of this pathogen. Ca. 20%
      of the expressed proteome changes 2-fold or more between the compared strains,
      including 42 proteins with literature or informatics annotations related to
      resistance mechanisms, modification of xenobiotics, or drug transport. Other
      categories of proteins differing 2-fold or more between strains include stress
      response related proteins, porins, OMPs, transporters and secretion-related
      proteins, cell wall- and expolysaccharide-related proteins, lipoproteins, and DNA
      and plasmid-related proteins. While the compared strains also differ in other
      aspects than multi-drug resistance, the observed differences, combined with
      protein functional annotation, suggest that complex protein expression changes
      may accompany the MDR phenotype. Expression changes of nine proteins in the MDR
      strain can potentially account for the observed resistance to 18 antibiotics.

PMID- 23542355
TI  - Integrated use of antioxidant enzymes and oxidative damage in two fish species to
      assess pollution in man-made hydroelectric reservoirs.
AB  - This study investigated the relationship between contaminant body burden and the
      oxidative stress status of the gills and livers of two wild fish species in the
      Furnas Hydroelectric Power Station (HPS) reservoir (Minas Gerais, Brazil). Gills
      and livers presented similar pathways of metals and organochlorine
      bioaccumulation. During June, organochlorines were associated with lipid
      peroxidation (LPO), indicating oxidative stress due to the inhibition of the
      antioxidant enzymes superoxide dismutase and glutathione peroxidase. In the most
      polluted areas, metal concentrations in the liver were associated with
      metallothionein. During December, contaminants in the gills and liver were
      associated with catalase activity and LPO. Aldrin/dieldrin was the contaminant
      most associated with oxidative damage in the livers of both species. This
      integrated approach shed light on the relationship between adverse biological
      effects and bioaccumulation of contaminants inputted by intensive agricultural
      practices and proved to be a suitable tool for assessing the environmental
      quality of man-made reservoirs.

PMID- 23542357
TI  - Sodium-dependent taurocholic cotransporting polypeptide: a candidate receptor for
      human hepatitis B virus.

PMID- 23542356
TI  - Acquired resistance to EGFR inhibitors is associated with a manifestation of stem
      cell-like properties in cancer cells.
AB  - Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) is a
      critical problem in the treatment of lung cancer. Although several mechanisms
      have been shown to be responsible for acquired resistance, all mechanisms have
      not been uncovered. In this study, we investigated the molecular and cellular
      profiles of the acquired resistant cells to EGFR-TKI in EGFR-mutant lung cancers.
      Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation and
      high-concentration exposure methods, and resistant sublines to gefitinib were
      established. The molecular profiles and cellular phenotypes of these resistant
      sublines were characterized. Although previously reported, alterations including
      secondary EGFR T790M mutation, MET amplification, and appearance of epithelial-to
      mesenchymal transition (EMT) features were observed, these 2 drug-exposure
      methods revealed different resistance mechanisms. The resistant cells with EMT
      features exhibited downregulation of miRNA-200c by DNA methylation. Furthermore,
      the HCC827-derived subline characterized by the high-concentration exposure
      method exhibited not only EMT features but also stem cell-like properties,
      including aldehyde dehydrogenase isoform 1 (ALDH1A1) overexpression, increase of
      side-population, and self-renewal capability. Resistant sublines with stem cell
      like properties were resistant to conventional chemotherapeutic agents but
      equally sensitive to histone deacetylase and proteasome inhibitors, compared with
      their parental cells. ALDH1A1 was upregulated in clinical samples with acquired
      resistance to gefitinib. In conclusion, our study indicates that the manner of
      EGFR-TKI exposure influences the mechanism of acquired resistance and the
      appearance of stem cell-like property with EGFR-TKI treatment.

PMID- 23542359
TI  - To the editor - a novel algorithm for synchronized left ventricular pacing and
      ambulatory optimization of cardiac resynchronization therapy.

PMID- 23542360
TI  - Reply to the editor - a novel algorithm for synchronized left ventricular pacing
      and ambulatory optimization of cardiac resynchronization therapy.

PMID- 23542361
TI  - Delayed intrinsicoid deflection onset in surface ECG lateral leads predicts left
      ventricular reverse remodeling after cardiac resynchronization therapy.
AB  - BACKGROUND: Up to one-third of the patients who undergo cardiac resynchronization
      therapy (CRT) are not responders. OBJECTIVE: To demonstrate that delayed lateral
      left ventricular activation time determined through time to intrinsicoid
      deflection onset (ID) predicts response after CRT. METHODS: The ID in leads I,
      aVL, V1 and V2, and V5 and V6 were measured in 135 patients who underwent CRT. A
      CRT response was defined as a decrease in left ventricular end-systolic volume
      (LVESV) exceeding 15% at 6 months. RESULTS: In patients with left bundle branch
      block or nonspecific intraventricular conduction delay, response was predicted by
      longer ID in lead I (odds ratio [OR] 3.23; 95% confidence interval (CI) 1.4-7.4;
      per 20-ms increase), in lead aVL (OR 3.0; 95% CI 1.2-7.3; per 20-ms increase),
      and in lead I minus lead V1 (OR 2.4; 95% CI 1.2-4.7) adjusting for baseline QRS
      duration and LVESV. Results were similar after adjusting for postimplant or
      change in QRS duration. The ID parameters were better predictors of response than
      QRS duration parameters. ID in lead I/QRS duration ratio (OR 3.1; 95% CI 1.6-5.9)
      also increased the odds of response after adjusting for baseline LVESV. Cutoff
      values for ID in leads--I, 110 ms; aVL, 130 ms; I minus V1, 90 ms--and ID in lead
      I/QRS duration ratio of 0.69 yielded a sensitivity and a specificity as high as
      83% and 81%. CONCLUSIONS: Measurement of ID on surface electrocardiography
      permits a preimplant, noninvasive means of determining left ventricle activation
      delay; is a good predictor of CRT response; and represents a promising
      alternative to QRS duration parameters.

PMID- 23542363
TI  - From the editor.

PMID- 23542364
TI  - Organizational coherence in health care organizations: conceptual guidance to
      facilitate quality improvement and organizational change.
AB  - OBJECTIVE: We sought to improve our understanding of how health care quality
      improvement (QI) methods and innovations could be efficiently and effectively
      translated between settings to reduce persistent gaps in health care quality both
      within and across countries. We aimed to examine whether we could identify a core
      set of organizational cultural attributes, independent of context and setting,
      which might be associated with success in implementing and sustaining QI systems
      in health care organizations. METHODS: We convened an international group of
      investigators to explore the issues of organizational culture and QI in different
      health care contexts and settings. This group met in person 3 times and held a
      series of conference calls to discuss emerging ideas over 2 years. Investigators
      also conducted pilot studies in their home countries to examine the applicability
      of our conceptual model. RESULTS AND CONCLUSIONS: We suggest that organizational
      coherence may be a critical element of QI efforts in health care organizations
      and propose that there are 3 key components of organizational coherence: (1)
      people, (2) processes, and (3) perspectives. Our work suggests that the concept
      of organizational coherence embraces both culture and context and can thus help
      guide both researchers and practitioners in efforts to enhance health care QI
      efforts, regardless of organizational type, location, or context.

PMID- 23542362
TI  - Redox regulation of SIRT1 in inflammation and cellular senescence.
AB  - Sirtuin 1 (SIRT1) regulates inflammation, aging (life span and health span),
      calorie restriction/energetics, mitochondrial biogenesis, stress resistance,
      cellular senescence, endothelial functions, apoptosis/autophagy, and circadian
      rhythms through deacetylation of transcription factors and histones. SIRT1 level
      and activity are decreased in chronic inflammatory conditions and aging, in which
      oxidative stress occurs. SIRT1 is regulated by a NAD(+)-dependent DNA repair
      enzyme, poly(ADP-ribose) polymerase-1 (PARP1), and subsequent NAD(+) depletion by
      oxidative stress may have consequent effects on inflammatory and stress responses
      as well as cellular senescence. SIRT1 has been shown to undergo covalent
      oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to
      posttranslational modifications, inactivation, and protein degradation.
      Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the
      loss of its control on acetylation of target proteins including p53, RelA/p65,
      and FOXO3, thereby enhancing the inflammatory, prosenescent, and apoptotic
      responses, as well as endothelial dysfunction. In this review, the mechanisms of
      cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1
      and its roles in PARP1 and NF-kappaB activation, and FOXO3 and eNOS regulation,
      as well as chromatin remodeling/histone modifications during inflammaging, are
      discussed. Furthermore, we have also discussed various novel ways to activate
      SIRT1 either directly or indirectly, which may have therapeutic potential in
      attenuating inflammation and premature senescence involved in chronic lung
      diseases. 

PMID- 23542365
TI  - Development and validation of a cystic fibrosis patient and family member
      experience of care survey.
AB  - OBJECTIVE: The purpose of this study was to develop a cystic fibrosis (CF)
      specific patient and family experience of care survey that CF care centers could
      use to inform quality improvement efforts. METHODS: A literature search and query
      of CF care centers was conducted to identify existing surveys. Individuals with
      CF, their families, and health care professionals were also asked what to
      include. Following this process, a draft survey was developed and then reviewed
      by focus groups. Finally, a version was piloted at 25 CF care centers to validate
      and further refine the instrument. RESULTS: No CF-specific surveys were found in
      the literature. Focus group participants stated that they understood the survey
      questions and that they covered important aspects of care, particularly infection
      control. The pilot test of the instrument with 485 participants supported its
      validity by demonstrating significant differences across centers and that most of
      the 3 care dimensions had acceptable internal consistency (Cronbach alpha:
      adults, 0.71-0.85; children, 0.68-0.79). CONCLUSION: A CF-specific patient and
      family experience of care survey was developed with input from individuals with
      CF, their families, and health care professionals. The instrument was validated
      and has been deployed to CF care centers.

PMID- 23542366
TI  - Awareness of evidence-based practices alone does not translate to implementation:
      insights from implementation research.
AB  - This article offers a scholarly review and perspective on the potential of
      "implementation research" to generate incremental, context-sensitive, evidence
      based management strategies for the successful implementation of evidence-based
      practices (EBPs) (such as the "central line bundle"). Many hospitals have
      difficulty consistently implementing EBPs at the unit level. This problem has
      been broadly characterized as "change implementation failure" in health care
      organizations. The popular hospital response to this challenge has been to raise
      clinician awareness of EBPs through mandated educational programs. However, this
      approach has not always succeeded in changing practice. The health services
      research literature has emphasized the role of several organizational variables
      (eg, leadership, safety culture, organizational learning, teamwork and
      communication, and physician/staff engagement) in successful change
      implementation. Correspondingly, this literature has developed broad frameworks
      and programs for change in health care organizations. While these broad change
      frameworks have been successfully applied by some facilities to change practice,
      they are not incrementally actionable. As such, several facilities have not
      leveraged broad change frameworks because of resource and/or contextual
      limitations; a majority of hospitals continue to resort to mandated clinician
      education (awareness-building) for change implementation. The recent impetus
      toward "implementation research" in health care has the potential to generate
      incremental, context-sensitive, evidence-based management strategies for practice
      change. Authors discuss specific insights from a recently completed study on
      central line bundle implementation in 2 intensive care units in an academic
      health center. The study demonstrates that awareness of EBPs alone does not
      translate to implementation. More importantly, the study also identifies
      incremental, context-sensitive, evidence-based management strategies for
      successful implementation of EBPs at the unit level.

PMID- 23542367
TI  - One lens missing? Clarifying the clinical microsystem framework with learning
      theories.
AB  - INTRODUCTION: The clinical microsystem (CMS) approach is widely used and is
      perceived as helpful in practice but, we ask the question: "Is its learning
      potential sufficiently utilized?" OBJECTIVES: To scrutinize aspects of learning
      within the CMS framework and to clarify the learning aspects the framework
      includes and thereby support the framework with the enhanced learning perspective
      that becomes visible. METHODS: Literature on the CMS framework was systematically
      searched and selected using inclusion criteria. An analytical tool was
      constructed in the form of a theoretical lens that was used to clarify learning
      aspects that are associated with the framework. FINDINGS: The analysis revealed 3
      learning aspects: (1) The CMS framework describes individual and social learning
      but not how to adapt learning strategies for purposes of change. (2) The
      metaphorical language of how to reach a holistic health care system for each
      patient has developed over time but can still be improved by naming social
      interactions to transcend organizational boundaries. (3) Power structures are
      recognized but not as a characteristic that restricts learning due to asymmetric
      communication. CONCLUSION: The "lens" perspective reveals new meanings to
      learning that enhance our understanding of health care as a social system and
      provides new practical learning strategies.

PMID- 23542368
TI  - Integrating patient- and family-centered care with health policy: four proposed
      policy approaches.
AB  - Achieving patient-centeredness in health care delivery has been difficult, in
      large part due to the lack of a replicable methodology. We describe the Patient-
      and Family-Centered Care Methodology and Practice (PFCC M/P), designed
      specifically for health care, to establish and sustain patient-centeredness in
      any care setting. The PFCC M/P meets the needs of all stakeholders--patients,
      families, providers, payers, and government--in improving the patient experience,
      patient safety, and clinical outcomes while decreasing waste and cost. We also
      propose options for aligning the PFCC M/P with policy as a means of bringing
      about widespread transformation in health care delivery.

PMID- 23542369
TI  - The utilization of standardized order sets using AASLD guidelines for patients
      with suspected cirrhosis and acute gastrointestinal bleeding.
AB  - To improve the adherence to AASLD (American Association for the Study of Liver
      Diseases) guidelines for variceal bleeding, we developed and implemented
      standardized order sets for gastrointestinal bleeding in our hospital on October
      1, 2009. We performed medical record reviews of hospitalized patients with
      gastrointestinal bleeding with suspected cirrhosis from October 2009 to October
      2010 to determine the use of octreotide, prophylactic antibiotics, and endoscopy.
      We reviewed 300 Medical records and identified 26 patients with suspected
      cirrhosis and gastrointestinal bleeding who had adequate information to determine
      whether or not the order set was used. Antibiotic was used in 76% of patients,
      octreotide was used in 76% of patients, and upper endoscopy was completed in 94%
      of patients within 24 hours. The use of antibiotics was higher than that used in
      historical controls in our hospital. Implementation of standardized order sets
      appears to have improved adherence to standard recommendations. However, larger
      studies with longer follow-ups are needed to evaluate this effect on clinical
      outcomes and cost of care.

PMID- 23542370
TI  - Managers' views and experiences of a large-scale county council improvement
      program: limitations and opportunities.
AB  - The aim of this study was to explore and evaluate managers' views of a large
      scale improvement program, including their experiences and opinions about
      improvement initiatives and drivers for change. The study is based on a survey
      used in 2 nationwide mappings of improvement initiatives and developmental trends
      in Swedish health care. The participants were all managers in a county council in
      Sweden. Data were analyzed descriptively, and statements were ranked in order of
      preferences. A majority of the respondents stated that they had worked with
      improvements since the county council improvement program started. The managers
      sometimes found it difficult to find data and measurements that supported the
      improvements, yet a majority considered that it was worth the effort and that the
      improvement work yielded results. The top-ranked driving forces were ideas from
      personnel and problems in the daily work. Staff satisfaction was ranked highest
      of the improvement potentials, but issues about patients' experiences of their
      care and patient safety came second and third. The managers stated that no or
      only a few patients had been involved in their improvement initiatives. Large
      scale county council improvement initiatives can illuminate quality problems and
      lead to increased interest in improvement initiatives in the health care sector.

PMID- 23542371
TI  - Timely response to secure messages from primary care patients.
AB  - PURPOSE: To assess delays in response to patient secure e-mail messages in
      primary care. BACKGROUND: Secure electronic messages are initiated by primary
      care patients. Timely response is necessary for patient safety and quality. DATA
      SOURCE: A database of secure messages. SAMPLE: A random sample of 353 secure
      electronic messages initiated by primary care patients treated in 4 clinics.
      OUTCOME MEASURES: Message not opened after 12 hours or messages not responded to
      after 36 hours. RESULTS: A total of 8.5% of electronic messages were not opened
      within 12 hours, and 17.6% did not receive a response in 36 hours. Clinic
      location, being a clinic employee, and patient sex were not related to delays.
      Patients older than 50 years were more likely to receive a delayed response
      (25.7% delayed, P = .013). The risk of both kinds of delays was higher on
      weekends (P < .001 for both). CONCLUSION: The e-mail message system resulted in
      high rates of delayed response. Delays were concentrated on weekends (Friday
      Sunday). Reducing delayed responses may require automatic rerouting of messages
      to message centers staffed 24-7 or other mechanisms to manage this after-hours
      work flow.

PMID- 23542374
TI  - A method of 2D/3D registration of a statistical mouse atlas with a planar X-ray
      projection and an optical photo.
AB  - The development of sophisticated and high throughput whole body small animal
      imaging technologies has created a need for improved image analysis and increased
      automation. The registration of a digital mouse atlas to individual images is a
      prerequisite for automated organ segmentation and uptake quantification. This
      paper presents a fully-automatic method for registering a statistical mouse atlas
      with individual subjects based on an anterior-posterior X-ray projection and a
      lateral optical photo of the mouse silhouette. The mouse atlas was trained as a
      statistical shape model based on 83 organ-segmented micro-CT images. For
      registration, a hierarchical approach is applied which first registers high
      contrast organs, and then estimates low contrast organs based on the registered
      high contrast organs. To register the high contrast organs, a 2D-registration
      back-projection strategy is used that deforms the 3D atlas based on the 2D
      registrations of the atlas projections. For validation, this method was evaluated
      using 55 subjects of preclinical mouse studies. The results showed that this
      method can compensate for moderate variations of animal postures and organ
      anatomy. Two different metrics, the Dice coefficient and the average surface
      distance, were used to assess the registration accuracy of major organs. The Dice
      coefficients vary from 0.31 +/- 0.16 for the spleen to 0.88 +/- 0.03 for the
      whole body, and the average surface distance varies from 0.54 +/- 0.06 mm for the
      lungs to 0.85 +/- 0.10mm for the skin. The method was compared with a direct 3D
      deformation optimization (without 2D-registration-back-projection) and a single
      subject atlas registration (instead of using the statistical atlas). The
      comparison revealed that the 2D-registration-back-projection strategy
      significantly improved the registration accuracy, and the use of the statistical
      mouse atlas led to more plausible organ shapes than the single-subject atlas.
      This method was also tested with shoulder xenograft tumor-bearing mice, and the
      results showed that the registration accuracy of most organs was not
      significantly affected by the presence of shoulder tumors, except for the lungs
      and the spleen.

PMID- 23542376
TI  - Costs of illness for melanoma and nonmelanoma skin cancer in Denmark.
AB  - Incidences of melanoma and nonmelanoma skin cancer are high and increasing in
      many countries including Denmark. The diseases are highly preventable. We have
      estimated the healthcare costs of these cancers by comparing costs for cohorts of
      patients and matched controls in a national register-based study in Denmark. All
      incident patients with a diagnosis of melanoma, basal cell carcinoma, or squamous
      cell carcinoma in the period 2004-2008 were included. Four control individuals
      for each case were matched in terms of sex, age, and area of residence.
      Healthcare costs and productivity loss for patients and controls were estimated
      using Danish health and social registries 3 years before and 3 years after
      diagnosis. The healthcare costs of melanoma and nonmelanoma skin cancer were
      &OV0556;33.3 million in the 3-year period after diagnosis, with male patients
      inducing the highest costs for all three cancers and costs increasing with age.
      The diagnoses of basal cell carcinoma and melanoma had almost the same healthcare
      costs, but per patient average healthcare costs were higher for melanoma. The
      costs of melanoma and nonmelanoma skin cancers, which can be prevented by
      sensible sun habits, exceed the costs of the preventive measures of the Danish
      SunSmart campaign manifold. Costs of melanoma and nonmelanoma skin cancer are
      expected to increase in the future with populations aging in the western world.
      The analyses provide a strong argument for the societal rationale of skin cancer
      prevention in Denmark. 

PMID- 23542375
TI  - Molecular control of the amount, subcellular location, and activity state of
      translation elongation factor 2 in neurons experiencing stress.
AB  - Eukaryotic elongation factor 2 (eEF-2) is an important regulator of the protein
      translation machinery whereby it controls the movement of the ribosome along the
      mRNA. The activity of eEF-2 is regulated by changes in cellular energy status and
      nutrient availability and by posttranslational modifications such as
      phosphorylation and mono-ADP-ribosylation. However, the mechanisms regulating
      protein translation under conditions of cellular stress in neurons are unknown.
      Here we show that when rat hippocampal neurons experience oxidative stress (lipid
      peroxidation induced by exposure to cumene hydroperoxide; CH), eEF-2 is
      hyperphosphorylated and ribosylated, resulting in reduced translational activity.
      The degradation of eEF-2 requires calpain proteolytic activity and is accompanied
      by accumulation of eEF-2 in the nuclear compartment. The subcellular localization
      of both native and phosphorylated forms of eEF-2 is influenced by CRM1 and
      14.3.3, respectively. In hippocampal neurons p53 interacts with nonphosphorylated
      (active) eEF-2, but not with its phosphorylated form. The p53-eEF-2 complexes are
      present in cytoplasm and nucleus, and their abundance increases when neurons
      experience oxidative stress. The nuclear localization of active eEF-2 depends
      upon its interaction with p53, as cells lacking p53 contain less active eEF-2 in
      the nuclear compartment. Overexpression of eEF-2 in hippocampal neurons results
      in increased nuclear levels of eEF-2 and decreased cell death after exposure to
      CH. Our results reveal novel molecular mechanisms controlling the differential
      subcellular localization and activity state of eEF-2 that may influence the
      survival status of neurons during periods of elevated oxidative stress. 

PMID- 23542377
TI  - Molecular dynamics of ion transport through the open conformation of a bacterial
      voltage-gated sodium channel.
AB  - The crystal structure of the open conformation of a bacterial voltage-gated
      sodium channel pore from Magnetococcus sp. (NaVMs) has provided the basis for a
      molecular dynamics study defining the channel's full ion translocation pathway
      and conductance process, selectivity, electrophysiological characteristics, and
      ion-binding sites. Microsecond molecular dynamics simulations permitted a
      complete time-course characterization of the protein in a membrane system,
      capturing the plethora of conductance events and revealing a complex mixture of
      single and multi-ion phenomena with decoupled rapid bidirectional water
      transport. The simulations suggest specific localization sites for the sodium
      ions, which correspond with experimentally determined electron density found in
      the selectivity filter of the crystal structure. These studies have also allowed
      us to identify the ion conductance mechanism and its relation to water movement
      for the NavMs channel pore and to make realistic predictions of its conductance
      properties. The calculated single-channel conductance and selectivity ratio
      correspond closely with the electrophysiology measurements of the NavMs channel
      expressed in HEK 293 cells. The ion translocation process seen in this voltage
      gated sodium channel is clearly different from that exhibited by members of the
      closely related family of voltage-gated potassium channels and also differs
      considerably from existing proposals for the conductance process in sodium
      channels. These studies simulate sodium channel conductance based on an
      experimentally determined structure of a sodium channel pore that has a
      completely open transmembrane pathway and activation gate.

PMID- 23542378
TI  - Using a preclinical mouse model of high-grade astrocytoma to optimize p53
      restoration therapy.
AB  - Based on clinical presentation, glioblastoma (GBM) is stratified into primary and
      secondary types. The protein 53 (p53) pathway is functionally incapacitated in
      most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis,
      we used a GFAP-HRas(V12) mouse model crossed into the p53ER(TAM) background, such
      that either one or both copies of endogenous p53 is replaced by a conditional
      p53ER(TAM) allele. The p53ER(TAM) protein can be toggled reversibly in vivo
      between wild-type and inactive conformations by administration or withdrawal of 4
      hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in
      GFAP-HRas(V12);p53(+/KI) mice abrogate the p53 pathway by mutating p19(ARF)/MDM2
      while retaining wild-type p53 allele. Consequently, such tumors are unaffected by
      restoration of their p53ER(TAM) allele. By contrast, gliomas arising in GFAP
      HRas(V12);p53(KI/KI) mice develop in the absence of functional p53. Such tumors
      retain a functional p19(ARF)/MDM2-signaling pathway, and restoration of
      p53ER(TAM) allele triggers p53-tumor-suppressor activity. Congruently, growth
      inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in
      human GBM cultures also requires p14(ARF)/MDM2 functionality. Notably, the
      antitumoral efficacy of p53 restoration in tumor-bearing GFAP
      HRas(V12);p53(KI/KI) animals depends on the duration and frequency of p53
      restoration. Thus, intermittent exposure to p53ER(TAM) activity mitigated the
      selective pressure to inactivate the p19(ARF)/MDM2/p53 pathway as a means of
      resistance, extending progression-free survival. Our results suggest that
      intermittent dosing regimes of drugs that restore wild-type tumor-suppressor
      function onto mutant, inactive p53 proteins will prove to be more efficacious
      than traditional chronic dosing by similarly reducing adaptive resistance.

PMID- 23542379
TI  - Dynamic scaffold of chiral binaphthol derivatives with the alkynylplatinum(II)
      terpyridine moiety.
AB  - Platinum(II)-containing complexes with inherently chiral binaphthol derivatives
      display a versatile scaffold between random coils and single-turn helical
      strands, in which the conformational transition is controlled by the Pt...Pt and
      pi-pi interactions of alkynylplatinum(II) terpyridine moiety upon solvent and
      temperature modulation. The bisignate Cotton effect in the circular dichroism
      spectra is indicative of the cooperative transformation from random coil state to
      a compact single-turn M- or P-helix. More importantly, as revealed by the
      appearance of new UV-vis absorption and emission bands during conformational
      change, the self-assembly of the platinum(II)-containing complex into a helical
      structure is assisted by the metal...metal and pi-pi interactions of the
      alkynylplatinum(II) terpyridine moieties. The folded structure with stabilization
      via metal...metal and pi-pi interactions has been supported by density functional
      theory calculations, which provide insights into the folded geometry of these
      kind of metallo-foldamers.

PMID- 23542381
TI  - Sensing conformational changes in metabotropic glutamate receptors.

PMID- 23542382
TI  - Increased axonal bouton dynamics in the aging mouse cortex.
AB  - Aging is a major risk factor for many neurological diseases and is associated
      with mild cognitive decline. Previous studies suggest that aging is accompanied
      by reduced synapse number and synaptic plasticity in specific brain regions.
      However, most studies, to date, used either postmortem or ex vivo preparations
      and lacked key in vivo evidence. Thus, whether neuronal arbors and synaptic
      structures remain dynamic in the intact aged brain and whether specific synaptic
      deficits arise during aging remains unknown. Here we used in vivo two-photon
      imaging and a unique analysis method to rigorously measure and track the size and
      location of axonal boutons in aged mice. Unexpectedly, the aged cortex shows
      circuit-specific increased rates of axonal bouton formation, elimination, and
      destabilization. Compared with the young adult brain, large (i.e., strong)
      boutons show 10-fold higher rates of destabilization and 20-fold higher turnover
      in the aged cortex. Size fluctuations of persistent boutons, believed to encode
      long-term memories, also are larger in the aged brain, whereas bouton size and
      density are not affected. Our data uncover a striking and unexpected increase in
      axonal bouton dynamics in the aged cortex. The increased turnover and
      destabilization rates of large boutons indicate that learning and memory deficits
      in the aged brain arise not through an inability to form new synapses but rather
      through decreased synaptic tenacity. Overall our study suggests that increased
      synaptic structural dynamics in specific cortical circuits may be a mechanism for
      age-related cognitive decline.

PMID- 23542383
TI  - A modification to the fascia-bone-fascia technique for repair of the middle fossa
      floor.
AB  - A commonly used method for resurfacing of the middle fossa floor is the fascia
      bone-fascia technique. One disadvantage of this technique however is the
      occasional migration of the bone graft. To prevent this, we have modified the
      technique to include securing of the graft using simple craniotomy fixation
      materials. We have now used this method in five patients, all of whom have had
      satisfactory clinical outcomes. Follow-up imaging has demonstrated the grafts to
      have remained in their original position.

PMID- 23542384
TI  - The influence of assortativity on the robustness and evolvability of gene
      regulatory networks upon gene birth.
AB  - Gene regulatory networks (GRNs) represent the interactions between genes and gene
      products, which drive the gene expression patterns that produce cellular
      phenotypes. GRNs display a number of characteristics that are beneficial for the
      development and evolution of organisms. For example, they are often robust to
      genetic perturbation, such as mutations in regulatory regions or loss of gene
      function. Simultaneously, GRNs are often evolvable as these genetic perturbations
      are occasionally exploited to innovate novel regulatory programs. Several
      topological properties, such as degree distribution, are known to influence the
      robustness and evolvability of GRNs. Assortativity, which measures the propensity
      of nodes of similar connectivity to connect to one another, is a separate
      topological property that has recently been shown to influence the robustness of
      GRNs to point mutations in cis-regulatory regions. However, it remains to be seen
      how assortativity may influence the robustness and evolvability of GRNs to other
      forms of genetic perturbation, such as gene birth via duplication or de novo
      origination. Here, we employ a computational model of genetic regulation to
      investigate whether the assortativity of a GRN influences its robustness and
      evolvability upon gene birth. We find that the robustness of a GRN generally
      increases with increasing assortativity, while its evolvability generally
      decreases. However, the rate of change in robustness outpaces that of
      evolvability, resulting in an increased proportion of assortative GRNs that are
      simultaneously robust and evolvable. By providing a mechanistic explanation for
      these observations, this work extends our understanding of how the assortativity
      of a GRN influences its robustness and evolvability upon gene birth.

PMID- 23542385
TI  - A study on the morphology of the suprascapular notch and its distance from the
      glenoid cavity.
AB  - INTRODUCTION: A suprascapular nerve entrapment can occur at the suprascapular
      notch or at the spinoglenoid notch. So, the size and shape of the suprascapular
      notch are associated with suprascapular entrapment neuropathy as well as with an
      injury to the suprascapular nerve in arthroscopic procedures. The knowledge on
      the variations along the course of the nerve is important in understanding the
      source of the entrapment syndrome. MATERIAL AND METHODS: The present study was
      carried out on 104 scapulae which were obtained from the Department of Anatomy,
      NRI Medical College and from other nearby medical colleges. The suprascapular
      notches in the scapulae were classified, based on the descriptions of Rengachary
      et al and Ticker et al. The distance between the suprascapular notch and the
      supraglenoid tubercle, and the distance between the posterior rim of the glenoid
      cavity and the medial wall of the spinoglenoid notch at the base of the scapular
      spine, were determined. The data were analyzed statistically. RESULTS: Based on
      the Rengachary classification, the type III notch was more common. The
      suprascapular foramen was observed in 2 scapulae. In 56.73% scapulae, the
      superior transverse diameter was greater than the maximum depth. The U shaped
      notch (69.23%) was more common. 2.88% and 8.65% scapulae fell short of the
      mentioned respective safe zone distances from the margin of the glenoid cavity.
      CONCLUSION: Such studies may be useful in understanding the role of the notch in
      causing nerve entrapment and to prevent iatrogenic nerve injuries while posterior
      approaches are made to the shoulder joint.

PMID- 23542386
TI  - Brain metastases: can we do more?

PMID- 23542387
TI  - Cerebral metastatic disease: applying what we know to rare brain metastases.

PMID- 23542388
TI  - Rerum magistra experientia est: the evolution of modern endoscopic endonasal
      skull base surgery and reconstruction techniques.

PMID- 23542389
TI  - A journey in neurosurgery.

PMID- 23542380
TI  - Phenotypic properties of transmitted founder HIV-1.
AB  - Defining the virus-host interactions responsible for HIV-1 transmission,
      including the phenotypic requirements of viruses capable of establishing de novo
      infections, could be important for AIDS vaccine development. Previous analyses
      have failed to identify phenotypic properties other than chemokine receptor 5
      (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral
      transmission. However, most of these studies were limited to examining envelope
      (Env) function in the context of pseudoviruses. Here, we generated infectious
      molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n =
      14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic
      properties in assays specifically designed to probe the earliest stages of HIV-1
      infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and
      contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF
      viruses were also captured by monocyte-derived dendritic cells 1.7-fold more
      efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025).
      In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics;
      however, when propagated in the presence of IFN-alpha, TF viruses replicated to
      higher titers than CC viruses. This difference was significant for subtype B (P =
      0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic
      differences of the respective patient cohorts. Together, these data indicate that
      TF viruses are enriched for higher Env content, enhanced cell-free infectivity,
      improved dendritic cell interaction, and relative IFN-alpha resistance. These
      viral properties, which likely act in concert, should be considered in the
      development and testing of AIDS vaccines.

PMID- 23542390
TI  - Management of giant internal carotid artery aneurysms.

PMID- 23542391
TI  - Higher prehospital priority level for stroke makes sense: the Hyper Acute STroke
      Alarm (HASTA) study.

PMID- 23542392
TI  - Training aneurysm surgeons in the modern era.

PMID- 23542393
TI  - Suprasellar approaches: new techniques and old tricks for cerebrospinal fluid
      leaks.

PMID- 23542394
TI  - Portrait of a life journey dedicated to neurosurgery.

PMID- 23542395
TI  - Cytological diagnosis of parasites presenting as superficial nodular swelling:
      report of 35 cases.
AB  - Parasitic infestation often present with superficial nodular swelling. Fine
      needle aspiration cytology plays an important role in prompt diagnosis of the
      disease. To study the role of FNAC in the diagnosis of parasites presenting as
      skin or subcutaneous nodules. Total 361 cases of superficial swellings at various
      sites were subjected to fine needle aspiration cytology. Out of the 361 cases, 35
      cases were diagnosed as suggestive of parasitic infestation. These 35 cases form
      the study group. In 14 cases out of 35 cases, a definitive diagnosis of parasitic
      infestation was made as parasite or fragments of parasite were seen in the
      aspirate. In 21 cases, neither parasite nor fragments could be identified on the
      aspirates and a diagnosis of parasitic inflammation was suggested on the basis of
      other cytomorphological findings. In 17 of these cases, a biopsy correlation was
      available, which revealed definitive parasite in 8 cases and the remaining 9 were
      reported as suggestive of parasitic cyst. The cytological diagnosis was
      confirmatory in cases where the parasite fragment were identified in the smears.
      However, in other cases, clear aspirate, presence of eosinophils, macrophages and
      typical granular dirty background are the features which should prompt the
      cytologist to the possibility of parasitic infestation.

PMID- 23542396
TI  - An obesogenic bias in women's spatial memory for high calorie snack food.
AB  - To help maintain a positive energy balance in ancestral human habitats, evolution
      appears to have designed a functional bias in spatial memory that enhances our
      ability to remember the location of high-calorie foodstuffs. Here, we
      investigated whether this functional bias has obesogenic consequences for
      individuals living in a modern urban environment. Spatial memory, dietary
      intentions, and perceived desirability, for high-calorie snacks and lower-calorie
      fruits and vegetables were measured using a computer-based task in 41 women (age:
      18-35, body mass index: 18.5-30.0). Using multiple linear regression, we analyzed
      whether enhanced spatial memory for high-calorie snacks versus fruits and
      vegetables predicted BMI, controlling for dietary intention strength and
      perceived food desirability. We observed that enhanced spatial memory for high
      calorie snacks (both independently, and relative to that for fruits and
      vegetables), significantly predicted higher BMI. The evolved function of high
      calorie bias in human spatial memory, to promote positive energy balance, would
      therefore appear to be intact. But our data reveal that this function may
      contribute to higher, less healthy BMI in individuals in whom the memory bias is
      most marked. Our findings reveal a novel cognitive marker of vulnerability to
      weight gain that, once the proximal mechanisms are understood, may offer new
      possibilities for weight control interventions.

PMID- 23542397
TI  - Ultrasound guided fnac of abdominal-pelvic masses-the pathologists' perspective.
AB  - INTRODUCTION: Fine Needle Aspiration(FNA) which is used for making a cytologic
      diagnosis has become an indispensable component of the work-up of many
      abnormalities.The objectives of this study were to adopt USG guided fine needle
      aspiration in the diagnosis of abdomino-pelvic masses, to assess its efficacy and
      to study the cytological features of abdominopelvic masses. MATERIALS AND
      METHODS: Hundred patients with clinically or sonologically diagnosed abdomino
      pelvic masses were taken up for the study. FNAC was performed under real time USG
      guidance. The aspirates were smeared onto a minimum of 2 slides and they were
      routinely stained with H&E, MGG and Papanicolaou stains. OBSERVATIONS: The
      diagnostic accuracy rates of USG guided FNAC for benign, malignant and non
      neoplastic lesions were 100%,96% and 94.4% respectively.The overall accuracy rate
      was 96.3%. CONCLUSION: USG guided FNAC is a rapid , economical,non-invasive,
      highly accurate and a safe diagnostic procedure which can pre-empt a lengthy and
      expensive workup in various abdomino- pelviv masses.

PMID- 23542398
TI  - A study of surgical management of diabetic limb complications among rural
      population.
AB  - Surgical complication of diabetes mellitus has been a common clinical problem
      among the rural population because of illiteracy and poor health education. The
      present study was undertaken to evaluate patients with respect to age, sex,
      presentation and to do other specific investigations. The patients were treated
      by conservative or surgical methods, and the outcome was monitored. The majority
      of the patients were males with peak age group in the sixth decade. Septic
      lesions were more than the neuropathic or the ischaemic lesions.

PMID- 23542399
TI  - Organ Specific Tumor Markers: What's New?
AB  - Tumor markers are molecules produced in the body in response to cancer. An ideal
      tumor marker should have high sensitivity and specificity, should be cheap, and
      should be easily detected in body fluids. Identification of novel markers is
      important and it is expected that with the advent of newer technologies, more
      reliable markers will be discovered. This review discusses the currently
      available tumor markers for different malignancies.

PMID- 23542400
TI  - Massive amounts of tissue factor induce fibrinogenolysis without tissue
      hypoperfusion in rats.
AB  - Trauma-induced tissue factor (TF) release into the systemic circulation is
      considered to play an important role in the development of disseminated
      intravascular coagulation (DIC) immediately after severe trauma. However, the
      relationship between TF and hyperfibrinolysis, especially fibrinogenolysis, has
      been unclear. A total of 18 rats were divided into three groups: (a) the control
      group was infused with normal saline; (b) the low-dose group was infused with 4
      U/kg TF; and (c) the high-dose group was infused with 16 U/kg TF. Arterial blood
      was drawn immediately and 2 and 4 h after the start of TF infusion. At each
      sampling point, arterial blood gases, platelet counts, and coagulation variables
      were measured. The fibrinogen degradation products were evaluated by a Western
      blot analysis. Hypotension, hypoxemia, and lactic acidosis were not observed in
      any of the three groups. In proportion to the doses of TF, the platelet counts,
      coagulation, and fibrinolysis variables deteriorated in line with DIC. The alpha2
      plasmin inhibitor levels significantly decreased in the high-dose group compared
      with the other groups. The amounts of fibrinogen degradation products increased
      in proportion to the doses of TF. The plasmin-alpha2-plasmin inhibitor complex
      level in the high-dose group increased more than that of the other groups. In
      conclusion, TF can induce DIC associated with fibrinolysis and fibrinogenolysis
      without tissue hypoperfusion. The decrease in the alpha2-plasmin inhibitor level
      and the significant increase in the plasmin level may be the two main factors
      underlying the pathogenesis of hyperfibrin(ogen)olysis after TF administration.

PMID- 23542401
TI  - Early trauma-hemorrhage-induced splenic and thymic apoptosis is gut-mediated and
      toll-like receptor 4-dependent.
AB  - Immune depression after trauma-hemorrhage has been implicated as an important
      factor in the pathogenesis of sepsis and septic-organ failure. Although recent
      studies have implicated immune-cell apoptosis as an important factor in the
      evolution of this posttrauma immune-suppressed state, neither the initial
      triggers that induce this response nor the cellular pathways through which these
      triggering pathways act have been fully defined. Thus, the current study tests
      the hypothesis that acute splenic and thymic immune-cell apoptosis developing
      after trauma-hemorrhagic shock (T/HS) is due to gut-derived factors carried in
      intestinal lymph and that this T/HS lymph-induced immune depressed state is
      mediated through Toll-like receptor 4 (TLR4). The first set of experiments
      documented that T/HS caused both thymic and splenic immune-cell apoptosis as
      measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)
      and caspase-3 immunohistochemistry and that this increase in apoptosis was
      totally abrogated by mesenteric lymph duct ligation. In subsequent experiments,
      mesenteric lymph collected from animals subjected to T/HS or trauma-sham shock
      were injected into TLR4-deficient (TLR4mut) mice or their wild-type (WT)
      littermates. Trauma-hemorrhagic shock, but not trauma-sham shock, lymph caused
      splenic apoptosis in the WT mice. However, the TLR4mut mice were resistant to
      T/HS lymph-induced splenic apoptosis. Furthermore, the WT, but not the TLR4mut
      mice developed splenic apoptosis after actual T/HS. In conclusion, gut-derived
      factors appear to initiate a sequence of events that leads to an acute increase
      in splenic and thymic immune-cell apoptosis, and this process is TLR4-dependent.

PMID- 23542402
TI  - Development of a self-report physical function instrument for disability
      assessment: item pool construction and factor analysis.
AB  - OBJECTIVES: To build a comprehensive item pool representing work-relevant
      physical functioning and to test the factor structure of the item pool. These
      developmental steps represent initial outcomes of a broader project to develop
      instruments for the assessment of function within the context of Social Security
      Administration (SSA) disability programs. DESIGN: Comprehensive literature
      review; gap analysis; item generation with expert panel input; stakeholder
      interviews; cognitive interviews; cross-sectional survey administration; and
      exploratory and confirmatory factor analyses to assess item pool structure.
      SETTING: In-person and semistructured interviews and Internet and telephone
      surveys. PARTICIPANTS: Sample of SSA claimants (n=1017) and a normative sample of
      adults from the U.S. general population (n=999). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURE: Model fit statistics. RESULTS: The final item pool
      consisted of 139 items. Within the claimant sample, 58.7% were white; 31.8% were
      black; 46.6% were women; and the mean age was 49.7 years. Initial factor analyses
      revealed a 4-factor solution, which included more items and allowed separate
      characterization of: (1) changing and maintaining body position, (2) whole body
      mobility, (3) upper body function, and (4) upper extremity fine motor. The final
      4-factor model included 91 items. Confirmatory factor analyses for the 4-factor
      models for the claimant and the normative samples demonstrated very good fit. Fit
      statistics for claimant and normative samples, respectively, were: Comparative
      Fit Index=.93 and .98; Tucker-Lewis Index=.92 and .98; and root mean square error
      approximation=.05 and .04. CONCLUSIONS: The factor structure of the physical
      function item pool closely resembled the hypothesized content model. The 4 scales
      relevant to work activities offer promise for providing reliable information
      about claimant physical functioning relevant to work disability.

PMID- 23542403
TI  - Amputee locomotion: determining the inertial properties of running-specific
      prostheses.
AB  - OBJECTIVES: (1) To test the validity of a trifilar pendulum in estimating moments
      of inertia (MOIs) for running-specific prostheses (RSPs), (2) to measure inertial
      properties (mass, center of mass [CM] position, and MOIs) for 4 RSPs, (3) to
      verify the influence of the stiffness on the inertial properties of RSPs, and (4)
      to develop a predictive equation to estimate RSP CM positions. DESIGN: An
      aluminum block with known MOIs was used for verifying the accuracy of the
      trifilar pendulum MOI measurements. MOI errors were investigated by
      systematically misaligning the block and pendulum principal axes across a range
      of 1 to 10cm. Mass, CM position, and MOI were tested across 4 RSP designs with 3
      stiffness categories each. SETTING: University biomechanics laboratory.
      SPECIMENS: Four different RSP designs and 3 stiffness categories per design were
      examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: MOI errors from
      known values and principal axis misalignments between RSPs and pendulum; mass, CM
      positions, and RSP principal axis MOIs; and predictive equation CM position
      errors. RESULTS: The trifilar pendulum estimated MOIs within -6.21*10(-5)kg/m(2)
      (<=1% error) for a block with known MOIs. Misalignments of 1 to 5cm between the
      RSPs' and pendulum's CM yielded errors from .00002 to .00113 kg/m(2) (0.3%
      59.2%). Each RSP's inertial properties are presented. MOIs about any axis varied
      <.004kg/m(2) across stiffness categories; MOIs differed up to .013kg/m(2) between
      different designs. The predictive CM equation erred between .010 and .028m when
      using average input values across an RSP design. CONCLUSIONS: Trifilar pendulums
      can accurately measure RSP MOI. The RSP inertial properties differed slightly
      across stiffness categories within each design, but differed more substantially
      across different RSP designs. Using a predictive equation to estimate RSP CM
      positions can provide adequate data, but directly measuring CM positions is
      preferable.

PMID- 23542404
TI  - Scale refinement and initial evaluation of a behavioral health function
      measurement tool for work disability evaluation.
AB  - OBJECTIVE: To use item response theory (IRT) data simulations to construct and
      perform initial psychometric testing of a newly developed instrument, the Social
      Security Administration Behavioral Health Function (SSA-BH) instrument, that aims
      to assess behavioral health functioning relevant to the context of work. DESIGN:
      Cross-sectional survey followed by IRT calibration data simulations. SETTING:
      Community. PARTICIPANTS: Sample of individuals applying for Social Security
      Administration disability benefits: claimants (n=1015) and a normative
      comparative sample of U.S. adults (n=1000). INTERVENTIONS: None. MAIN OUTCOME
      MEASURE: SSA-BH measurement instrument. RESULTS: IRT analyses supported the
      unidimensionality of 4 SSA-BH scales: mood and emotions (35 items), self-efficacy
      (23 items), social interactions (6 items), and behavioral control (15 items). All
      SSA-BH scales demonstrated strong psychometric properties including reliability,
      accuracy, and breadth of coverage. High correlations of the simulated 5- or 10
      item computer adaptive tests with the full item bank indicated robust ability of
      the computer adaptive testing approach to comprehensively characterize behavioral
      health function along 4 distinct dimensions. CONCLUSIONS: Initial testing and
      evaluation of the SSA-BH instrument demonstrated good accuracy, reliability, and
      content coverage along all 4 scales. Behavioral function profiles of Social
      Security Administration claimants were generated and compared with age- and sex
      matched norms along 4 scales: mood and emotions, behavioral control, social
      interactions, and self-efficacy. Using the computer adaptive test-based approach
      offers the ability to collect standardized, comprehensive functional information
      about claimants in an efficient way, which may prove useful in the context of the
      Social Security Administration's work disability programs.

PMID- 23542406
TI  - High diagnostic ability of multiparametric magnetic resonance imaging to detect
      anterior prostate cancer missed by transrectal 12-core biopsy.
AB  - PURPOSE: We clarified the diagnostic ability of multiparametric magnetic
      resonance imaging to reveal anterior cancer missed by transrectal 12-core
      prostate biopsy based on the results of 3-dimensional 26-core prostate biopsy,
      which is a combination of transrectal 12-core and transperineal 14-core biopsies.
      MATERIALS AND METHODS: The study population consisted of 324 patients who
      prospectively underwent prebiopsy multiparametric magnetic resonance imaging and
      then 3-dimensional 26-core prostate biopsy at a single institution. We defined
      transrectal 12-core negative cancer as cancer detected by transperineal 14-core
      but not transrectal 12-core prostate biopsy. We focused on cancer in the anterior
      region. Any findings suspicious for malignancy in the region anterior to the
      urethra on multiparametric magnetic resonance imaging were defined as an anterior
      lesion on imaging. Significant cancer was defined as a biopsy Gleason score of 4
      + 3 or greater, a greater than 20% positive core and/or a maximum cancer length
      of 5 mm or greater. Associations between an anterior lesion on imaging and
      transrectal 12-core negative cancer were investigated. RESULTS: The overall
      cancer detection rate on 3-dimensional 26-core prostate biopsy was 39% (128 of
      324 cases), of which 28% (36 of 128) were transrectal 12-core negative cancers.
      An anterior lesion on prebiopsy multiparametric magnetic resonance imaging was
      identified in 20% of men overall (65 of 324). Of men with and without an anterior
      lesion on imaging 40% (26 of 65) and 3.8% (10 of 259), respectively, had
      transrectal 12-core negative cancer. Significant transrectal 12-core negative
      cancer was observed in 0.4% (1 of 259 men) without an anterior lesion on imaging.
      Prebiopsy multiparametric magnetic resonance imaging revealed an anterior lesion
      in 92% of cases (11 of 12) of significant transrectal 12-core negative cancer.
      CONCLUSIONS: Prebiopsy multiparametric magnetic resonance imaging has the
      potential to efficiently select men who could advantageously undergo anterior
      samplings, in addition to transrectal 12-core prostate biopsy.

PMID- 23542407
TI  - Mechanisms of pelvic organ cross-talk: 2. Impact of colorectal distention on
      afferent nerve activity of the rat bladder.
AB  - PURPOSE: Pelvic organ neural cross-talk is mediated by central and peripheral
      pathways. We investigated the effects of colorectal distention at the peripheral
      level on mechanosensitive bladder single unit afferent activity. MATERIALS AND
      METHODS: We used 16 female Sprague-Dawley(r) rats in this study. The single unit
      afferent activity of nerves originating from the bladder were identified by
      electrical stimulation of the pelvic nerve and by bladder distention. They were
      classified by conduction velocity as C or Adelta fibers. After measuring single
      unit afferent activity during constant bladder filling without colorectal
      distention, measurements during bladder filling were repeated with colorectal
      distention at 20, 40 and 60 mm Hg. To evaluate the convergence of bladder and
      colorectal afferent fibers, rapid colorectal distention was performed with an
      empty bladder. Bladder afferent fibers with an increased response to rapid
      colorectal distention were defined as convergent fibers and the others were
      defined as nonconvergent fibers. RESULTS: A total of 30 single units (19 C and 11
      Adelta fibers) were isolated. Continuous colorectal distention increased the
      bladder single unit afferent activity of C and Adelta fibers in a pressure
      dependent manner. C fibers could be divided into convergent (12) and
      nonconvergent (7) fibers but all Adelta fibers were nonconvergent. The
      facilitatory effect of continuous colorectal distention on bladder single unit
      afferent activity was absent in nonconvergent C fibers. CONCLUSIONS: In rats the
      convergence of bladder and colorectal peripheral nerves was
      electrophysiologically identified only in mechanosensitive C fibers and not in
      Adelta fibers. Continuous colorectal distention probably increased the bladder
      single unit afferent activity of C fibers through direct convergence at the
      peripheral level between the bladder and sensory ganglia. It probably increased
      the bladder single unit afferent activity of Adelta fibers through an alternative
      pathway.

PMID- 23542408
TI  - Slow mapping: color word learning as a gradual inductive process.
AB  - Most current accounts of color word acquisition propose that the delay between
      children's first production of color words and adult-like understanding is due to
      problems abstracting color as a domain of meaning. Here we present evidence
      against this hypothesis, and show that, from the time children produce color
      words in a labeling task they use them to represent color. In Experiment 1, an
      analysis of early color word errors finds that, before acquiring adult-like
      understanding, children make systematic hypotheses about color word meanings,
      which are best characterized as overextensions of adult meanings. Using a
      comprehension task, Experiment 2 finds that these overextensions are due to
      overly broad color categories, rather than a communicative strategy. These
      results indicate that the delay between production and adult-like understanding
      of color words is not due to difficulties abstracting color, but is largely
      attributable to the problem of determining the color boundaries marked by
      specific languages.

PMID- 23542405
TI  - The expanding bacterial type IV secretion lexicon.
AB  - The bacterial type IV secretion systems (T4SSs) comprise a biologically diverse
      group of translocation systems functioning to deliver DNA or protein substrates
      from donor to target cells generally by a mechanism dependent on establishment of
      direct cell-to-cell contact. Members of one T4SS subfamily, the conjugation
      systems, mediate the widespread and rapid dissemination of antibiotic resistance
      and virulence traits among bacterial pathogens. Members of a second subfamily,
      the effector translocators, are used by often medically-important pathogens to
      deliver effector proteins to eukaryotic target cells during the course of
      infection. Here we summarize our current understanding of the structural and
      functional diversity of T4SSs and of the evolutionary processes shaping this
      diversity. We compare mechanistic and architectural features of T4SSs from Gram
      negative and -positive species. Finally, we introduce the concept of the
      'minimized' T4SSs; these are systems composed of a conserved set of 5-6 subunits
      that are distributed among many Gram-positive and some Gram-negative species.

PMID- 23542409
TI  - Spatial language facilitates spatial cognition: evidence from children who lack
      language input.
AB  - Does spatial language influence how people think about space? To address this
      question, we observed children who did not know a conventional language, and
      tested their performance on nonlinguistic spatial tasks. We studied deaf children
      living in Istanbul whose hearing losses prevented them from acquiring speech and
      whose hearing parents had not exposed them to sign. Lacking a conventional
      language, the children used gestures, called homesigns, to communicate. In Study
      1, we asked whether homesigners used gesture to convey spatial relations, and
      found that they did not. In Study 2, we tested a new group of homesigners on a
      Spatial Mapping Task, and found that they performed significantly worse than
      hearing Turkish children who were matched to the deaf children on another
      cognitive task. The absence of spatial language thus went hand-in-hand with poor
      performance on the nonlinguistic spatial task, pointing to the importance of
      spatial language in thinking about space.

PMID- 23542410
TI  - Do young children have adult-like syntactic categories? Zipf's law and the case
      of the determiner.
AB  - Generativist models of grammatical development assume that children have adult
      like grammatical categories from the earliest observable stages, whereas
      constructivist models assume that children's early categories are more limited in
      scope. In the present paper, we test these assumptions with respect to one
      particular syntactic category, the determiner. This is done by comparing
      controlled measures of overlap in the set of nouns with which children and their
      caregivers use different instances of the determiner category in their
      spontaneous speech. In a series of studies, we show, first, that it is important
      to control for both sample size and vocabulary range when comparing child and
      adult overlap measures; second, that, once the appropriate controls have been
      applied, there is significantly less overlap in the nouns with which young
      children use the determiners a/an and the in their speech than in the nouns with
      which their caregivers use these same determiners; and, third, that the level of
      (controlled) overlap in the nouns that the children use with the determiners a/an
      and the increases significantly over the course of development. The implication
      is that children do not have an adult-like determiner category during the
      earliest observable stages, and that their knowledge of the determiner category
      only gradually approximates that of adults as a function of their linguistic
      experience.

PMID- 23542411
TI  - Intersubjective action-effect binding: eye contact modulates acquisition of
      bidirectional association between our and others' actions.
AB  - In everyday social life, we predict others' actions in response to our own
      actions. Subsequently, on the basis of these predictions, we control our actions
      to attain desired social outcomes and/or adjust our actions to accommodate the
      anticipated actions of the others. Representation of the bidirectional
      association between our and others' actions, that is, intersubjective action
      effect binding, could make such intersubjective action control easier and
      smoother. The present study investigated not only whether or not intersubjective
      action-effect binding was acquired but also whether or not eye contact modulated
      it. Experiment 1 showed that after a repeated experience during which
      participants' finger movements triggered a target female individual's mouth
      gesture, observing the target's mouth gestures came to automatically trigger the
      participants' finger movements. Experiments 2 and 3 revealed that this effect was
      not observed when the target's gaze direction was averted (Experiment 2) or when
      the target's eyes were closed (Experiment 3) throughout the acquisition phase.
      These results indicate that intersubjective action-effect binding occurs and that
      an ostensive signal, that is, eye contact modulates it.

PMID- 23542412
TI  - The acquisition of abstract words by young infants.
AB  - Young infants' learning of words for abstract concepts like 'all gone' and 'eat,'
      in contrast to their learning of more concrete words like 'apple' and 'shoe,' may
      follow a relatively protracted developmental course. We examined whether infants
      know such abstract words. Parents named one of two events shown in side-by-side
      videos while their 6-16-month-old infants (n=98) watched. On average, infants
      successfully looked at the named video by 10 months, but not earlier, and
      infants' looking at the named referent increased robustly at around 14 months.
      Six-month-olds already understand concrete words in this task (Bergelson &
      Swingley, 2012). A video-corpus analysis of unscripted mother-infant interaction
      showed that mothers used the tested abstract words less often in the presence of
      their referent events than they used concrete words in the presence of their
      referent objects. We suggest that referential uncertainty in abstract words'
      teaching conditions may explain the later acquisition of abstract than concrete
      words, and we discuss the possible role of changes in social-cognitive abilities
      over the 6-14 month period.

PMID- 23542413
TI  - Protection from antimycin A-induced mitochondrial dysfunction by Nelumbo nucifera
      seed extracts.
AB  - Antimycin A (AMA) damages the mitochondria through inhibition of mitochondrial
      electron transport. In this study, exposure of L6 rat skeletal muscle cells to
      AMA induced a decrease in ATP content, followed by a decrease in mitochondrial
      membrane potential, leading to apoptosis. We evaluated the protective effects of
      water and ethanol extracts of Nelumbo nucifera seeds on L6 cells with AMA-induced
      oxidative stress. We found that the extracts reduced cellular apoptosis;
      preserved the mitochondrial membrane potential; protected mitochondrial ATP
      production; inhibited p53, Bax, and caspase 3 activities; and induced Bcl-2
      production. Our results suggested that AMA induced apoptosis in L6 cells via
      impairment of mitochondrial function. N. nucifera extracts protected the cells
      from this mitochondria-mediated cell death.

PMID- 23542414
TI  - Predicting the effect of ionising radiation on biological populations: testing of
      a non-linear Leslie model applied to a small mammal population.
AB  - The present work describes the application of a non-linear Leslie model for
      predicting the effects of ionising radiation on wild populations. The model
      assumes that, for protracted chronic irradiation, the effect-dose relationship is
      linear. In particular, the effects of radiation are modelled by relating the
      increase in the mortality rates of the individuals to the dose rates through a
      proportionality factor C. The model was tested using independent data and
      information from a series of experiments that were aimed at assessing the
      response to radiation of wild populations of meadow voles and whose results were
      described in the international literature. The comparison of the model results
      with the data selected from the above mentioned experiments showed that the model
      overestimated the detrimental effects of radiation on the size of irradiated
      populations when the values of C were within the range derived from the median
      lethal dose (L50) for small mammals. The described non-linear model suggests that
      the non-expressed biotic potential of the species whose growth is limited by
      processes of environmental resistance, such as the competition among the
      individuals of the same or of different species for the exploitation of the
      available resources, can be a factor that determines a more effective response of
      population to the radiation effects.

PMID- 23542415
TI  - Incidental experiences of affective coherence and incoherence influence
      persuasion.
AB  - When affective experiences are inconsistent with activated evaluative concepts,
      people experience what is called affective incoherence; when affective
      experiences are consistent with activated evaluative concepts, people experience
      affective coherence. The present research asked whether incidental feelings of
      affective coherence and incoherence would regulate persuasion. Experiences of
      affective coherence and incoherence were predicted and found to influence the
      processing of persuasive messages when evoked prior to receipt of such messages
      (Experiments 1 and 3), and to influence the confidence with which thoughts
      generated by persuasive messages were held when evoked after presentation of such
      messages (Experiments 2 and 3). These results extend research on affective
      coherence and incoherence by showing that they exert a broader impact on
      cognitive activity than originally assumed.

PMID- 23542416
TI  - Cultural variation in the focus on goals versus processes of actions.
AB  - Everyday actions (e.g., riding a bike) can be described in ways that emphasize
      either the goals of the action by adapting a higher level identification (e.g.,
      getting exercise) or the processes of the action by adapting a lower level
      identification (e.g., pedaling). In Studies 1 and 2, we demonstrate cultural
      differences in focusing on the process or goal of actions at the individual
      level: Americans are more likely than Japanese to focus on the goal (rather than
      the process) of actions. Study 3 recruited Chinese participants in addition to
      American and Japanese participants and found that cultural differences in action
      identification are partly explained by cultural differences in self-consistency.
      Study 4 further showed cultural differences at the collective level: American
      media presents more goal-oriented information and less process-oriented
      information than does Japanese media. These findings highlight the role of
      culture in shaping how people attend to different aspects of actions.

PMID- 23542417
TI  - Changes in the haemato-biochemical pattern due to experimentally induced
      haemonchosis in Sahabadi sheep.
AB  - The study evaluated the damage caused by Haemonchus contortus in terms of blood
      loss, faecal clearance of plasma protein and elevated serum enzyme activity in
      Sahabadi sheep. Apparently healthy Sahabadi sheep (n = 15) were selected randomly
      based on phenotypic characteristics and divided into two groups; infected (n = 8)
      and uninfected control (n = 6) and one sheep was used as donor animal. Each
      animal of infected group were orally infected with 700 third stage larvae (L3) of
      H. contortus/kg body weight. Blood from all the fourteen animals were collected
      at weekly intervals starting from day one to 42 day post infection. Parameters
      studied were haemoglobin concentration (Hb), packed cell volume (PCV), total
      erythrocyte count (TEC), total serum protein, serum albumin, serum globulin,
      alkaline phosphatase, Alanine amino transferase and Aspartate amino transferase.
      Statistical analysis showed that significant decreases in Hb, PCV, TEC and serum
      protein concentration and significant increases in serum enzymes level in
      infected sheep compared to uninfected control. The present study concluded that
      experimental H. contortus infection caused disturbances to the haemopoietic
      system resulting anaemia and severe damage to abomasal mucosa resulting lower
      serum protein and higher enzyme activities.

PMID- 23542418
TI  - MicroRNA-191, an estrogen-responsive microRNA, functions as an oncogenic
      regulator in human breast cancer.
AB  - Estrogen- and microRNA-mediated gene regulation play a crucial role in breast
      cancer biology. However, a functional link between the two major players remains
      unclear. This study reveals miR-191 as an estrogen-inducible onco-miR in breast
      cancer, which promotes several hallmarks of cancer including enhanced cell
      proliferation, migration, chemoresistance and survival in tumor microenvironment.
      miR-191 is a direct estrogen receptor (ER) target and our results suggest
      existence of a positive regulatory feedback loop. We show miR-191 as critical
      mediator of estrogen-mediated cell proliferation. Investigations of mechanistic
      details of miR-191 functions identify several cancer-related genes like BDNF,
      CDK6 and SATB1 as miR-191 targets. miR-191 and SATB1 show inverse correlation of
      expression. miR-191-mediated enhanced cell proliferation and migration are partly
      dependent on targeted downregulation of SATB1. Further, functional validation of
      estrogen:miR-191:SATB1 link suggests a cascade initiated by estrogen that induces
      miR-191 in ER-dependent manner to target SATB1, a global chromatin remodeler,
      thereby contributing to estrogen-specific gene signature to regulate genes like
      ANXA1, PIWIL2, CASP4, ESR1/ESR2, PLAC1 and SOCS2 involved in breast cancer
      progression and migration. Overall, the identification of estrogen/ER/miR
      191/SATB1 cascade seems to be a significant pathway in estrogen signaling in
      breast cancer with miR-191 as oncogenic player. 

PMID- 23542419
TI  - Rationale and design of a randomized controlled, clinical trial investigating a
      comprehensive exercise stimulus for improving mobility disability outcomes in
      persons with multiple sclerosis.
AB  - This randomized controlled trial (RCT) examines the effect of a comprehensive
      exercise training stimulus on physiological function and mobility disability
      (i.e., problems walking) in individuals with multiple sclerosis (MS) who have
      walking impairment. This trial will recruit 30 persons with MS across central
      Illinois who have an Expanded Disability Status Scale score between 4.0 and 6.0,
      and those persons will be randomized into either the intervention or control arm
      of the study; the participants will not be blinded regarding group assignment.
      The intervention will incorporate equal amounts of aerobic, resistance, and
      balance modes of training delivered 3 times/week with a gradual progression of
      duration and intensity across a 6-month period. The control will involve
      stretching along with minimal muscle strengthening stimuli and will be delivered
      on the same frequency and duration. The primary outcomes will be clinical,
      kinematic, patient-rated, and physiological measures of mobility disability. The
      secondary outcomes will be measures of physiological function including aerobic
      capacity, muscle strength, and balance. This study will lay the foundation for
      the design of a subsequent Phase II or Phase III RCT by (a) providing effect
      sizes that can be included in a power analysis for sample size estimation and (b)
      investigating whether aerobic capacity, muscle strength, and balance are possible
      factors associated with the beneficial effect of exercise training on walking
      outcomes. Taken as a whole, the proposed study and our subsequent research agenda
      has the potential for advancing the management of mobility disability using
      exercise training in the 2nd stage of MS.

PMID- 23542420
TI  - Are two penicillins better than one? A systematic review of oral flucloxacillin
      and penicillin V versus oral flucloxacillin alone for the emergency department
      treatment of cellulitis.
AB  - BACKGROUND: Flucloxacillin either alone or combined with penicillin V is still
      the first-line antibiotic drug of choice for the treatment of cellulitis in
      emergency departments (EDs) in Ireland. The rationale for this antibiotic regimen
      is their anti-staphylococcal and anti-streptococcal activity. OBJECTIVE: To
      determine the clinical efficacy, tolerability and safety of oral flucloxacillin
      alone (monotherapy) compared with a combination of flucloxacillin with penicillin
      V (dual therapy) in the ED-directed outpatient treatment of cellulitis. METHODS:
      We searched the following electronic databases: MEDLINE (1950 to August 2011),
      EMBASE (1980 to August 2011), Cochrane Central Register of Controlled Clinical
      Trials (CENTRAL) (The Cochrane Library 2011, Issue), OpenGrey, Current Controlled
      Trials metaRegister of Clinical Trials (August 2011) and reference lists and
      websites of potential trials. We performed cross-referencing from the reference
      lists of major articles on the subject. We imposed no language restriction.
      RESULTS: Despite a comprehensive literature search to identify relevant studies,
      no randomized-controlled trials that fulfilled the inclusion criteria were found.
      CONCLUSIONS: Despite its common use, there are no published randomized-controlled
      trials comparing flucloxacillin monotherapy with a combination of flucloxacillin
      and penicillin V in the ED management of cellulitis. We discuss existing European
      and North American prescribing rationale and current guidelines.

PMID- 23542421
TI  - Impact of a working group on gastrointestinal decontamination in Spanish
      emergency departments.
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study is to analyze the impact of
      the actions carried out by the Intoxications Working Group (IWG) of Spanish
      Society of Pediatric Emergencies in the management of acute pediatric
      intoxications in Spain, specifically the publishing of a Handbook in 2004 or the
      creation of the Toxicologic Surveillance System in 2009. PATIENTS AND METHODS:
      Gastrointestinal decontamination procedures were analyzed in three periods of
      time in Pediatric Emergency Departments (PEDs) included in the IWG: group A (2001
      2002, 17 PED, 2157 episodes), group B (2008-2009, 22 PED, 612 episodes), and
      group C (2009-2011, 42 PED, 400 episodes). These periods were chosen because the
      main actions of the IWG were developed in the time in-between them. RESULTS: Of
      the 3169 episodes included, a gastrointestinal decontamination procedure was
      performed in 1031. The use of ipecac syrup decreased from 22.8% in group A to 0
      in group C and the performance of a gastric lavage decreased from 29.1% in group
      A to 26% in group C (NS), although on splitting yearly patients of group C, it
      decreased to 14.7% in 2011. CONCLUSION: Recommendations developed and spread by a
      Working Group have approached the management of acute pediatric intoxications in
      Spain to international guidelines on the basis of scientific evidence.

PMID- 23542423
TI  - A hyperplastic cause of hyperemesis.

PMID- 23542422
TI  - Towards robust deconvolution of low-dose perfusion CT: sparse perfusion
      deconvolution using online dictionary learning.
AB  - Computed tomography perfusion (CTP) is an important functional imaging modality
      in the evaluation of cerebrovascular diseases, particularly in acute stroke and
      vasospasm. However, the post-processed parametric maps of blood flow tend to be
      noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile
      and the oscillatory nature of the results generated by the current computational
      methods. In this paper, we propose a robust sparse perfusion deconvolution method
      (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We
      first build a dictionary from high-dose perfusion maps using online dictionary
      learning and then perform deconvolution-based hemodynamic parameters estimation
      on the low-dose CTP data. Our method is validated on clinical data of patients
      with normal and pathological CBF maps. The results show that we achieve superior
      performance than existing methods, and potentially improve the differentiation
      between normal and ischemic tissue in the brain.

PMID- 23542425
TI  - Two-partner secretion: as simple as it sounds?
AB  - The two-partner secretion (TPS) pathway is a branch of type V secretion. TPS
      systems are dedicated to the secretion across the outer membrane of long proteins
      that form extended beta-helices. They are composed of a 'TpsA' cargo protein and
      a 'TpsB' transporter, which belongs to the Omp85 superfamily. This basic design
      can be supplemented by additional components in some TPS systems. X-ray
      structures are available for the conserved TPS domain of several TpsA proteins
      and for one TpsB transporter. However, the molecular mechanisms of two-partner
      secretion remain to be deciphered, and in particular, the specific role(s) of the
      TPS domain and the conformational dynamics of the TpsB transporter. Deciphering
      the TPS pathway may reveal functional features of other transporters of the Omp85
      superfamily.

PMID- 23542424
TI  - Non classical secretion systems.
AB  - Bacteria use molecular machines or weapons to colonize, invade or fight other
      bacteria and eukaryotic cells. In addition to these various secretion systems,
      two different systems that release bacterial compounds have also been described.
      The first one corresponds to membrane vesicle formation and to long distance
      delivery of membrane or soluble components. The second system is dependent of the
      expression of the colicin lysis genes known for releasing cytoplasmic colicins as
      well as other soluble proteins. Both systems will be described thereafter. 

PMID- 23542426
TI  - The type II secretion system - a dynamic fiber assembly nanomachine.
AB  - Type II secretion systems (T2SSs) share common origins and structure with
      archaeal flagella (archaella) and pili, bacterial competence systems and type IV
      pili. All of these systems use a conserved ATP-powered machinery to assemble
      helical fibers that are anchored in the plasma membrane. The T2SSs assemble
      pseudopili, periplasmic filaments that promote extracellular secretion of folded
      periplasmic proteins. Comparative analysis of T2SSs and related fiber assembly
      nanomachines might provide important clues on their functional specificities and
      dynamics. This review focuses on recent developments in the study of pseudopilus
      structure and biogenesis, and discusses mechanistic models of pseudopilus
      function in protein secretion.

PMID- 23542427
TI  - Oxygen regulation of alternative respiration in fungus Phycomyces blakesleeanus:
      connection with phosphate metabolism.
AB  - Environmental changes can often result in oxygen deficiency which influences
      cellular energy metabolism, but such effects have been insufficiently studied in
      fungi. The effects of oxygen deprivation on respiration and phosphate metabolites
      in Phycomyces blakesleeanus were investigated by oxygen electrode and (31)P NMR
      spectroscopy. Mycelium was incubated in hypoxic and anoxic conditions for 1.5, 3
      and 5 h and then reoxygenated. Participation of alternative oxidase (AOX) in
      total respiration increased gradually in both treatments and after 5 h of anoxia
      exceeded a value 50% higher than in control. Shortly after reintroduction of
      oxygen into the system AOX level decreased close to the control level. Oxygen
      deprivation also caused a reversible decrease of polyphosphate/inorganic
      phosphate ratio (PPc/Pi), which was strongly correlated with the increase of AOX
      participation in total respiration. Unexpectedly, ATP content remained almost
      constant, probably due to the ability of PolyP to sustain energy and phosphate
      homeostasis of the cell under stress conditions. This was further substantiated
      by the effects of azide, a cytochrome c oxidase inhibitor, which also decreased
      PPc/Pi ratio, but to a smaller extent in oxygen deprived than control and
      reoxygenated specimens.

PMID- 23542428
TI  - The Type VI secretion system - a widespread and versatile cell targeting system.
AB  - The Type VI secretion system (T6SS) is the most recently described of the Gram
      negative bacterial secretion systems and is widely distributed amongst diverse
      species. T6SSs are currently believed to be complex molecular machines which
      inject effector proteins into target cells and which incorporate a bacteriophage
      like cell-puncturing device. T6SSs have been implicated in eukaryotic cell
      targeting and virulence in a range of important pathogens. More recently,
      'antibacterial' T6SSs have been reported, which are used to efficiently target
      competitor bacterial cells by the injection of antibacterial toxins. Although it
      is clear that T6SSs can be deployed as versatile weapons to compete with other
      bacteria or attack simple or higher eukaryotes, much remains to be determined
      about this intriguing system.

PMID- 23542429
TI  - Characterization of novel 3'untranslated regions and related polymorphisms of the
      gene NPPC, encoding for the C-type natriuretic peptide.
AB  - Elevated plasmatic levels of C-type natriuretic peptide (CNP) were found in
      patients with chronic heart failure (CHF), but its use as sensitive and specific
      clinical bio-marker is still controversial. In fact, high levels of CNP were also
      observed in patients classified in low severity New York Heart Association (NYHA)
      classes. CNP is encoded by a gene poorly studied (NPPC, natriuretic-precursor
      peptide C), where the regulatory regions are not well defined and the role of
      single nucleotide polymorphisms (SNPs) poorly ascertained. In the present work,
      we focused on the characterization of the 3'untranslated region (3'UTR) of the
      gene, using Rapid Amplification of cDNA 3'-End (3' RACE), and we identified two
      novel transcript isoforms (L-3'UTR; S-3'UTR; accession number JF420840, HQ419060
      respectively). Since it could be hypothesized that genetic variations could
      explain the observed inter-patients differences, we searched for novel SNPs, by
      the use of High Resolution Melting (HRM). The results showed a complete lack of
      genetic variations among our series of samples. Moreover, a preliminary
      evaluation, using literature information and bioinformatic prediction allowed us
      to predicted the putative relevant microRNAs binding to the novel 3'UTRs that
      could modulate the post-transcriptional regulation of NPPC and affect the
      plasmatic levels of CNP. We obtained 750 and 1024 predicted miRNAs targeting the
      S- and L-3'UTRs, respectively.

PMID- 23542430
TI  - High incidence of acute coronary occlusion in patients without protocol positive
      ST segment elevation referred to an open access primary angioplasty programme.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PPCI) programmes vary in
      admission criteria from open referral to acceptance of electrocardiogram (ECG)
      protocol positive patients only. Rigid criteria may result in some patients with
      acutely occluded coronary arteries not receiving timely reperfusion therapy.
      OBJECTIVE: To compare the prevalence of acute coronary occlusion and, in these
      cases, single time point biomarker estimates of myocardial infarct size between
      patients presenting with protocol positive ECG changes and those presenting with
      less diagnostic changes in the primary angioplasty cohort of an open access PPCI
      programme. METHODS: We retrospectively performed a single centre cross sectional
      analysis of consecutive patients receiving PPCI between January and August 2008.
      Cases were categorised according to presenting ECG-group A: protocol positive (ST
      segment elevation/left bundle branch block/posterior ST elevation myocardial
      infarction), group B: ST segment depression or T-wave inversion, or group C:
      minor ECG changes. Clinical characteristics, coronary flow grades and 12 h
      postprocedure troponin-I levels were reviewed. RESULTS: During the study period
      there were 513 activations of the PPCI service, of which 390 underwent immediate
      angiography and 308 underwent PPCI. Of those undergoing PPCI, 221 (72%) were in
      group A, 41 (13%) in group B and 46 (15%) in group C. Prevalence of coronary
      occlusion was 75% in group A compared with 73% in group B and 63% in group C.
      Median 12 h postintervention troponin-I (25th-75th percentile) for those with
      coronary occlusion was significantly higher in group A patients; 28.9 MUg/l (13.2
      58.5) versus 18.1 MUg/l (6.7-32.4) for group B (p=0.03); and 15.5 MUg/l (3.8
      22.0) for group C (p<0.001), suggesting greater infarct size in group A.
      CONCLUSIONS: A number of patients referred to an open access PPCI programme have
      protocol negative ECGs but myocardial infarction and acute coronary artery
      occlusion amenable to angioplasty.

PMID- 23542431
TI  - The development and validation of an internet-based training package for the
      management of perineal trauma following childbirth: MaternityPEARLS.
AB  - BACKGROUND: Birth-related perineal trauma has a major impact on women's health.
      Appropriate management of perineal injuries requires clinical knowledge and
      skill. At present, there is no agreement as to what constitutes an effective
      clinical training programme, despite the presence of sufficient evidence to
      support standardised perineal repair techniques. To address this deficiency, we
      developed and validated an interactive distance learning multi-professional
      training package called MaternityPEARLS. METHOD: MaternityPEARLS was developed as
      a comprehensive e-learning package in 2010. The main aim of the MaternityPEARLS
      project was to develop, refine and validate this multi-professional e-learning
      tool. The effect of MaternityPEARLS in improving clinical skills and knowledge
      was compared with two other training models; traditional training (lectures +
      model-based hands on training) and offline computer lab-based training. Midwives
      and obstetricians were recruited for each training modality from three maternity
      units. An analysis of covariance was done to assess the effects of clinical
      profession and years of experience on scoring within each group. Feedback on
      MaternityPEARLS was also collected from participants. The project started in
      January 2010 and was completed in December 2010. RESULTS: Thirty-eight
      participants were included in the study. Pretraining and post-training scores in
      each group showed considerable improvement in skill scores (p<0.001 in all
      groups). Mean changes were similar across all three groups for knowledge (3.24
      (SD 5.38), 3.00 (SD 3.74), 3.30 (SD 3.73)) and skill (25.34 (SD 8.96), 22.82 (SD
      9.24), 20.7 (SD 9.76)) in the traditional, offline computer lab-based and e
      learning groups, respectively. There was no evidence of any effect of clinical
      experience and baseline knowledge on outcomes. CONCLUSIONS: MaternityPEARLS is
      the first validated perineal trauma management e-learning package. It provides a
      level of improvement in skill and knowledge comparable to traditional methods of
      training. However, as an e-learning system, it has the advantage of ensuring the
      delivery of a standardised, continuously updated curriculum that has global
      accessibility.

PMID- 23542433
TI  - Occurrence and dissipation of three azole biocides climbazole, clotrimazole and
      miconazole in biosolid-amended soils.
AB  - This study investigated the occurrence and dissipation of three azole biocides
      climbazole, clotrimazole and miconazole in biosolid-amended soils of the three
      sites (Zhejiang, Hunan and Shandong) in China following three treatments (CK:
      control without biosolid application; T1: one biosolid application; T2: biosolid
      application every year). The results showed that climbazole, clotrimazole and
      miconazole were present in the biosolid and biosolid-amended soils, but absent in
      the control soils. In the soils treated with biosolids, the concentrations of
      climbazole, clotrimazole and miconazole were mostly lower in the Zhejiang soils
      than in the Shandong or Hunan soils, suggesting that these three biocides are
      more readily dissipated under the flooding condition. During the one year
      monitoring, the concentrations of climbazole, clotrimazole and miconazole in the
      biosolid-applied soils showed only slight variations. The dissipation half-lives
      for miconazole calculated under the field conditions of Shandong site were 440
      days for T1 and the half-lives for clotrimazole were 365 days for T2. The results
      suggested the persistence of these three biocides in the soil environments.

PMID- 23542434
TI  - Kinetics, equilibrium, and mechanisms of sorption and desorption of 17alpha
      ethinyl estradiol in two natural soils and their organic fractions.
AB  - A study was conducted on the kinetics, equilibrium, and mechanisms of sorption
      and desorption of 17alpha-ethinyl estradiol (EE2) in six sorbents, which were two
      natural soils (Bulk1 and Bulk2) and their fractions obtained by alkaline
      extraction, namely, humic acids (HA1 and HA2), and mineral-bond humins (MHU1 and
      MHU2). These sorbents, characterized by total organic carbon (TOC), black carbon
      (BC), gas adsorption and Fourier transform infrared spectra, were shown to be
      porous solids containing aromatic (hard carbon) and aliphatic carbon (soft
      carbon). The two-compartment first-order model fitted the kinetics of sorption
      very well (R(2)>0.990). The fast and slow sorption rate constants ranged from
      1.110 h(-1) and 0.026 h(-1) to 2.063 h(-1) and 0.067 h(-1), respectively. The
      slow sorption was attributed to the diffusion of EE2 in micropores rather than
      organic matter. The Freundlich model fitted the equilibrium of sorption and
      desorption very well. The nonlinearity of sorption took the order MHU>bulk
      soil>HA and was positively related to BC/TOC (p<0.01). The hysteresis in MHU2
      with higher BC/TOC was stronger than that in Bulk2 with lower BC/TOC, but a
      contrary observation was found in MHU1 and Bulk1. This contradictory phenomenon
      could be attributed to the location difference of hard carbon which greatly
      affected the desorption process. These findings could give an insight into the
      sorption mechanisms and promote an accurate model for the transport, fate and
      risk assessment of EE2 in the environment.

PMID- 23542432
TI  - Stage specific requirement of Gfralpha1 in the ureteric epithelium during kidney
      development.
AB  - Glial cell line-derived neurotrophic factor (GDNF) binds a coreceptor GDNF family
      receptor alpha1 (GFRalpha1) and forms a signaling complex with the receptor
      tyrosine kinase RET. GDNF-GFRalpha1-RET signaling activates cellular pathways
      that are required for normal induction of the ureteric bud (UB) from the Wolffian
      duct (WD). Failure of UB formation results in bilateral renal agenesis and
      perinatal lethality. Gfralpha1 is expressed in both the epithelial and
      mesenchymal compartments of the developing kidney while Ret expression is
      specific to the epithelium. The biological importance of Gfralpha1's wider tissue
      expression and its role in later kidney development are unclear. We discovered
      that conditional loss of Gfralpha1 in the WD epithelium prior to UB branching is
      sufficient to cause renal agenesis. This finding indicates that Gfralpha1
      expressed in the nonepithelial structures cannot compensate for this loss. To
      determine Gfralpha1's role in branching morphogenesis after UB induction we used
      an inducible Gfralpha1-specific Cre-deletor strain and deleted Gfralpha1 from the
      majority of UB tip cells post UB induction in vivo and in explant kidney
      cultures. We report that Gfralpha1 excision from the epithelia compartment after
      UB induction caused a modest reduction in branching morphogenesis. The loss of
      Gfralpha1 from UB-tip cells resulted in reduced cell proliferation and decreased
      activated ERK (pERK). Further, cells without Gfralpha1 expression are able to
      populate the branching UB tips. These findings delineate previously unclear
      biological roles of Gfralpha1 in the urinary tract and demonstrate its cell-type
      and stage-specific requirements in kidney development. 

PMID- 23542435
TI  - Geochemical signature and properties of sediment sources and alluvial sediments
      within the Lago Paranoa catchment, Brasilia DF: a study on anthropogenic
      introduced chemical elements in an urban river basin.
AB  - One of the largest urban agglomerations in Brazil is the capital Brasilia and its
      surrounding area. Due to fast urban sprawl and accelerated land use changes,
      available water supplies are near their limits. The water supply depends largely
      on surface water collected in reservoirs. There are increasing concerns regarding
      water shortages due to sediment aggradations, and of water quality due to
      geochemical modification of sediments from human activities. The concentration of
      18 chemical elements and five sediment properties was analyzed from different
      potential land-based sediment sources and deposited alluvial sediment within the
      Lago Paranoa catchment. The goal of this study was to assess the distribution of
      chemical elements and geochemical/physical properties of potential sediment
      sources in the Lago Paranoa catchment. Principal component analysis and
      hierarchical cluster analysis were used to investigate the influence of different
      land use types on the geochemistry of sediments. Geochemical fingerprints of
      anthropogenic activities were developed based on the results of the cluster
      analysis grouping. The anthropogenic input of land use specific geochemical
      elements was examined and quantified by the calculation of enrichment factors
      using the local geological background as reference. Through comparison of the
      geochemical signature of potential sediment sources and alluvial sediments of the
      Lago Paranoa and sub-catchments, the relative contribution of land use specific
      sediment sources to the sediment deposition of the main water reservoir were
      estimated. The existing findings suggest a strong relationship between land use
      and quantifiable features of sediment geochemistry and indicate that urban land
      use had the greatest responsibility for recent silting in the Lago Paranoa. This
      assessment helps to characterize the role of human activities in mixed-used
      watersheds on sediment properties, and provides essential information to guide
      management responses towards more effective source-reduction strategies.

PMID- 23542436
TI  - Composition, distribution and risk assessment of organochlorine pesticides in
      soils from the Midway Atoll, North Pacific Ocean.
AB  - Concentrations of legacy organochlorine pesticides (OCPs), including
      dichlorodiphenyltrichloroethane (DDT) and its metabolites (e.g., DDE and DDD),
      and hexachlorocyclohexanes (HCHs) were determined in 111 soil samples from the
      Midway Atoll. OCPs were found in all samples analyzed, with predominance of alpha
      HCH, p,p'-DDD and p,p'-DDT. The total concentrations ranged from 0 to 127 ng g(
      1) with a median concentration of 17 ng g(-1) for HCHs and 1.4 to 643 ng g(-1)
      with a median concentration of 168 ng g(-1) for DDTs. The possible degradation
      pathways and potential sources of DDTs and HCHs were investigated. The total
      concentrations of DDTs and HCHs were used to evaluate the cancer risk
      probabilities in humans via ingestion, dermal contact and inhalation of soil
      particles. Very low cancer risk was found in all soil samples caused by SigmaDDTs
      and SigmaHCHs.

PMID- 23542437
TI  - Maximum allowable values of the heavy metals in recycled water for household
      laundry.
AB  - Household laundry as a new end use of recycled water in dual reticulation systems
      has a great potential as the significant amount of potable water from urban
      households can be saved. However, there is still no sufficient evidence and
      supporting recycled water quality guidelines for this particular use. A key gap
      in knowledge is the impact of heavy metals in recycled water on clothes and
      washing machines. Thus, this study aims to determine the maximum allowable values
      (MAVs) of the heavy metals iron (Fe), lead (Pb), zinc (Zn), copper (Cu), and
      manganese (Mn) in recycled water for washing clothes in washing machines. Six
      different concentrations of each targeted metals were prepared in tap water for
      the washing machine experiments. The tearing/tensile strength tests were used for
      the assessment of cloth durability. MINITAB 16 as a statistical tool was used and
      ANOVA one way test was applied for the significance analysis (Turkey's test
      p<0.05). The results show that the MAVs of the heavy metals Fe, Pb, Zn, Cu and Mn
      were found to be 1 mg/l, 1 mg/l, 10 mg/l, 5 mg/l and 1 mg/l respectively in terms
      of cloth durability.

PMID- 23542438
TI  - Femoral neck stress fracture.
AB  - The patient was a 19-year-old woman who recently completed a military basic
      training program. She was evaluated by a physical therapist in a direct-access
      capacity for a chief complaint of anterior right hip pain that limited her
      ability to run. Due to the limited sensitivity of radiographs, magnetic resonance
      imaging of the right hip was obtained, which revealed a stress fracture of the
      right distal femoral neck.J Orthop Sports Phys Ther 2013;43(4):275.
      doi:10.2519/jospt.2013.0407.

PMID- 23542439
TI  - Neuroprotection by steroids after neurotrauma in organotypic spinal cord
      cultures: a key role for progesterone receptors and steroidal modulators of
      GABA(A) receptors.
AB  - Progesterone is neuroprotective after spinal cord injury, however its mechanism
      of action remains unexplored. Here we used organotypic spinal cord slice cultures
      from 3 weeks-old mice to evaluate the mechanisms of neuroprotection by
      progesterone and its 5alpha-reduced metabolites. In vitro spinal cord injury,
      using a weight drop model, induced a decrease in the number of motoneurons. This
      was correlated with an increase in the number of dying cells (PI+ cells) and in
      LDH release. Addition of 10 MUM of progesterone, 5alpha-dihydroprogesterone
      (5alpha-DHP) or allopregnanolone (3alpha, 5alpha-tetrahydroprogesterone) to the
      medium at the time of injury rescued the spinal cord slices from the effects of
      damage. Progesterone prevented membrane cell damage, motoneuron loss and cell
      death. These effects were not due to its bioconversion to 5alpha-DHP nor to
      allopregnanolone, as supported by the finasteride, an inhibitor of 5alpha
      reductase enzymes, and by the absence of 5alpha-reduced progesterone metabolites
      in the slices analyzed by gas chromatography-mass spectrometry. The
      neuroprotective effects of progesterone required PR as they could not be observed
      in slices from homozygous knockout PR(-/-) mice. Allopregnanolone treatment was
      also neuroprotective. Its effects were not due to its bioconversion back to
      5alpha-DHP, which can activate gene transcription via PR, because they were still
      observed in slices from knockout PR(-/-) mice. Allopregnanolone effects involved
      GABA(A) receptors, as they were inhibited by the selective GABA(A) receptor
      antagonist Gabazine, in both PR(+/+) and PR(-/-) mice. Altogether, these findings
      identify both PR and GABA(A) receptors as important targets for neuroprotection
      by progestagens after spinal cord injury.

PMID- 23542441
TI  - Cell adhesion and homeostatic synaptic plasticity.
AB  - At synapses, pre- and post-synaptic cells get in direct contact with each other
      via cell adhesion molecules (CAMs). Several CAMs have been identified at the
      neuromuscular junction and at central synapses, where they regulate synaptic
      strength, by recruiting scaffolding proteins, neurotransmitter receptors and
      synaptic vesicles in response to the binding of counter-receptors across the
      synaptic cleft. Many synapses are also surrounded by astrocytic processes and
      embedded in conspicuous extracellular matrix (ECM). It is now widely recognized
      that astrocytes play a central role in regulating the synaptic machinery by
      exchanging information with the neuronal elements via diffusible molecules and
      direct physical interactions; this has lead to the concept of the 'tri-partite
      synapse'. More recently, the term 'tetra-partite synapse' has been introduced to
      underlie the importance of ECM in shaping synaptic function by mediating
      interaction and signaling between neurons and astrocytes. Here, we will review
      how this integrated view of the synapse can help us understand homeostatic
      synaptic plasticity at the neuromuscular junction and in the central nervous
      system. We will explore how synaptic CAMs regulate two forms of homeostatic
      plasticity: (i) postsynaptic scaling of synaptic currents to counteract changes
      in neuronal network activity and (ii) the compensatory modulation of presynaptic
      neurotransmitter release in response to changes in postsynaptic efficacy. We will
      discuss recent findings on activity-dependent trans-synaptic signaling events and
      the role of cell adhesion in the feedback control of network activity. This
      article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'. 

PMID- 23542442
TI  - Central functional response to the novel peptide cannabinoid, hemopressin.
AB  - Hemopressin is the first peptide ligand to be described for the CB1 cannabinoid
      receptor. Hemopressin acts as an inverse agonist in vivo and can cross the blood
      brain barrier to both inhibit appetite and induce antinociception. Despite being
      highly effective, synthetic CB1 inverse agonists are limited therapeutically due
      to unwanted, over dampening of central reward pathways. However, hemopressin
      appears to have its effect on appetite by affecting satiety rather than reward,
      suggesting an alternative mode of action which might avoid adverse side effects.
      Here, to resolve the neuronal circuitry mediating hemopressin's actions, we have
      combined blood-oxygen-level-dependent, pharmacological-challenge magnetic
      resonance imaging with c-Fos functional activity mapping to compare brain regions
      responsive to systemic administration of hemopressin and the synthetic CB1
      inverse agonist, AM251. Using these complementary methods, we demonstrate that
      hemopressin activates distinct neuronal substrates within the brain, focused
      mainly on the feeding-related circuits of the mediobasal hypothalamus and in
      nociceptive regions of the periaqueductal grey (PAG) and dorsal raphe (DR). In
      contrast to AM251, there is a distinct lack of activation of the brain reward
      centres, such as the ventral tegmental area, nucleus accumbens and orbitofrontal
      cortex, which normally form a functional activity signature for the central
      action of synthetic CB1 receptor inverse agonists. Thus, hemopressin modulates
      the function of key feeding-related brain nuclei of the mediobasal hypothalamus,
      and descending pain pathways of the PAG and DR, and not higher limbic structures.
      Thus, hemopressin may offer behaviourally selective effects on nociception and
      appetite, without engaging reward pathways.

PMID- 23542440
TI  - Sensitization of restraint-induced corticosterone secretion after chronic
      restraint in rats: involvement of 5-HT7 receptors.
AB  - Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response
      to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day)
      as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced
      ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB
      656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5
      HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal
      glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA),
      and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI)
      in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals
      were subdivided into Treatment and No treatment groups. Treatment animals
      received an i.p. injection of vehicle or SB-656104; No Treatment animals received
      no injection. Sixty min later, Treatment animals were either decapitated with no
      further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min);
      hormone serum levels were measured. No Treatment animals were employed for the
      rest of measurements. CRS decreased body weight gain and increased adrenal
      weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a
      time of restraint-dependent manner; both responses were inhibited by SB-656104.
      Exposure to CRS abolished ACTH but magnified CORT responses to restraint as
      compared to CTRL conditions; SB-656104 had no effect on ACTH levels but
      significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was
      detected in magnocellular and parvocellular subdivisions of PVN and sparsely in
      adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but
      increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and
      5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio
      increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the
      adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of
      CRS animals. No TPH protein was detected in AG from both animal groups. Results
      suggest that CRS promotes endocrine disruption involving decreased ACTH and
      sensitized CORT responses to acute restraint. This phenomenon may be associated
      with increased function and expression of 5-HT7 receptors as well as 5-HT
      turnover in AG.

PMID- 23542443
TI  - Comparative effects of several cyclodextrins on the extraction of PAHs from an
      aged contaminated soil.
AB  - The objective of the present study was to characterise the polycyclic aromatic
      hydrocarbons (PAHs) content of an aged contaminated soil and to propose
      remediation techniques using cyclodextrins (CDs). Four CDs solutions were tested
      as soil decontamination tool and proved more efficient in extracting PAHs than
      when an aqueous solution was used; especially two chemically modified CDs
      resulted in higher extraction percentages than natural beta-CD. The highest
      extraction percentages were obtained for 3-ring PAHs, because of the appropriate
      size and shape of these compounds relative to those of the hydrophobic cavities
      of the CDs studied. A detailed mechanistic interpretation of the chemical
      modification of CDs on the extraction of the different PAHs has been performed,
      and connected with the role that the different hydrophobicities of the PAHs play
      in the extraction behaviour observed for the 16 PAHs, limiting their
      accessibility and the remaining risk of those PAHs not extractable by CDs.

PMID- 23542444
TI  - Sorption, dissolution and pH determine the long-term equilibration and toxicity
      of coated and uncoated ZnO nanoparticles in soil.
AB  - To assess the effect of long-term dissolution on bioavailability and toxicity,
      triethoxyoctylsilane coated and uncoated zinc oxide nanoparticles (ZnO-NP), non
      nano ZnO and ZnCl2 were equilibrated in natural soil for up to twelve months. Zn
      concentrations in pore water increased with time for all ZnO forms but peaked at
      intermediate concentrations of ZnO-NP and non-nano ZnO, while for coated ZnO-NP
      such a clear peak only was seen after 12 months. Dose-related increases in soil
      pH may explain decreased soluble Zn levels due to fixation of Zn released from
      ZnO at higher soil concentrations. At T = 0 uncoated ZnO-NP and non-nano ZnO were
      equally toxic to the springtail Folsomia candida, but not as toxic as coated ZnO
      NP, and ZnCl2 being most toxic. After three months equilibration toxicity to F.
      candida was already reduced for all Zn forms, except for coated ZnO-NP which
      showed reduced toxicity only after 12 months equilibration.

PMID- 23542445
TI  - Developmental effects of aerosols and coal burning particles in zebrafish
      embryos.
AB  - Embryo toxicity of particles generated by combustion processes is of special
      concern for human health. A significant part of these toxic effects is linked to
      the binding of some pollutants (like polycyclic aromatic hydrocarbons or PAHs) to
      the Aryl hydrocarbon Receptor (AhR) and the activation of target genes, like the
      cytochrome P4501A. This activity was analyzed for ambient air and coal-combustion
      particle extracts in zebrafish embryos (the cyp1aDarT assay) and in two single
      cell bioassays: the yeast-based YCM-RYA and the DR-luc (rat cells) assay.
      Observed AhR ligand activity of samples generally correlated to the predicted
      toxic effect according to their PAH composition, except for one of the coal
      combustion samples with an anomalously high activity in the cyp1aDarT assay. This
      sample induced deformities in zebrafish embryos. We concluded that the
      combination of morphological and molecular assays may detect embryonic toxic
      effects that cannot be predicted from chemical analyses or single-cell bioassays.

PMID- 23542446
TI  - Influence of land use on human bioaccessibility of metals in smelter-impacted
      soils.
AB  - An investigation was undertaken to evaluate the empirical model developed by
      Pelfrene et al. (2012), predicting the human bioaccessibility of Cd and Pb in
      smelter-contaminated agricultural topsoils, by including other soil uses: 50
      urban and 65 woody habitat topsoils collected in the same area. The results
      showed that land use significantly affected the pseudototal metal concentrations
      and their oral bioaccessibility. However, whatever the soil's physicochemical
      parameters and degree of contamination, the 'agricultural' model can be used to
      simulate metal gastric bioaccessibility in urban and woody habitat soils. To
      simulate gastrointestinal bioaccessibility, this model can be used directly if
      the pseudototal metal concentrations are on the same order of magnitude as those
      usually recorded in the agricultural soils studied or after the use of a
      correction factor if these concentrations are greater. These results showed that
      the oral bioaccessibility predictions could be applicable for further
      environmental risk evaluation.

PMID- 23542448
TI  - Photochemical trapping heterogeneity as a function of wavelength, in plant
      photosystem I (PSI-LHCI).
AB  - In the present paper the marked changes in photochemical trapping time over the
      absorption/fluorescence band of isolated PSI-LHCI are studied by means of time
      resolved fluorescence decay measurements. For emission at 680-690nm the effective
      trapping time is close to 17-18ps, and represents the effective trapping time
      from the bulk antenna. At wavelengths above 700nm the effective trapping time
      increases in a monotonic way, over the entire emission band, to attain values in
      the range of 70-80ps near 760nm. This is argued to be caused by "uphill" energy
      transfer from the low energy states to the core antenna and reaction centre.
      These data, together with the steady state emission spectrum, permit calculation
      of the overall trapping time for maize PSI-LHCI, which is estimated to be
      approximately 40ps. The wavelength dependence of the trapping time indicates,
      that in PSI-LHCI there exists at least one red form which emits at lower energies
      than the 735nm state. These data indicate that Photosystem I is about 55%
      diffusion limited.

PMID- 23542447
TI  - Molecular mechanisms of superoxide production by complex III: a bacterial versus
      human mitochondrial comparative case study.
AB  - In this mini review, we briefly survey the molecular processes that lead to
      reactive oxygen species (ROS) production by the respiratory complex III (CIII or
      cytochrome bc1). In particular, we discuss the "forward" and "reverse" electron
      transfer pathways that lead to superoxide generation at the quinol oxidation (Qo)
      site of CIII, and the components that affect these reactions. We then describe
      and compare the properties of a bacterial (Rhodobacter capsulatus) mutant enzyme
      producing ROS with its mitochondrial (human cybrids) counterpart associated with
      a disease. The mutation under study is located at a highly conserved tyrosine
      residue of cytochrome b (Y302C in R. capsulatus and Y278C in human mitochondria)
      that is at the heart of the quinol oxidation (Qo) site of CIII. Similarities of
      the major findings of bacterial and human mitochondrial cases, including
      decreased catalytic activity of CIII, enhanced ROS production and ensuing
      cellular responses and damages, are remarkable. This case illustrates the
      usefulness of undertaking parallel and complementary studies using biologically
      different yet evolutionarily related systems, such as alpha-proteobacteria and
      human mitochondria. It progresses our understanding of CIII mechanism of function
      and ROS production, and underlines the possible importance of supra-molecular
      organization of bacterial and mitochondrial respiratory chains (i.e.,
      respirasomes) and their potential disease-associated protective roles. This
      article is part of a Special Issue entitled: Respiratory complex III and related
      bc complexes. 

PMID- 23542449
TI  - Endoscopic stenting for malignant hilar biliary obstruction: should it be metal
      or plastic and unilateral or bilateral?
AB  - BACKGROUND: Endoscopic biliary drainage is the palliative treatment of choice for
      malignant biliary hilar obstruction. There are conflicting opinions as to whether
      stents should be plastic or metal and whether stents should be unilateral or
      bilateral. AIM: To systematically review the literature on optimal endoscopic
      management of malignant hilar biliary obstruction. METHODS: A comprehensive
      search of several databases was carried out. A fixed-effect or a random-effect
      model was used to pool the data according to the result of a statistical
      heterogeneity test. RESULTS: Ten trials were enrolled. Compared with plastic
      stents, the use of metal stents was associated with a significantly higher
      successful drainage rate [odds ratio (OR) 0.26; 95% confidence interval (CI) 0.16
      0.42; I2=40.3%], lower early complication rate (OR 2.92; 95% CI 1.65-5.17;
      I2=0%), longer stent patency [hazard ratio (HR) 0.43; 95% CI 0.30-0.61;
      I2=57.6%], and longer patient survival (HR 0.73; 95% CI 0.56-0.96; I2=56.9%). The
      unilateral biliary drainage group achieved a significantly higher successful
      stent insertion rate compared with the bilateral drainage group (OR 3.44; 95% CI
      1.91-6.19; I2=0%), whereas no difference was observed between groups with respect
      to successful drainage rate (OR 1.73; 95% CI 0.89-3.37; I2=0%), early
      complications (OR 0.96; 95% CI 0.18-5.13; I2=60.4%), late complications (OR 1.41;
      95% CI 0.54-3.67; I2=70.4%), stent patency (HR 0.57; 95% CI 0.19-1.73; I2=91.1%),
      and patient survival (HR 0.75; 95% CI 0.31-1.80; I2=94.3%). CONCLUSION: The
      performance of metallic stents was superior to that of plastic stents for hilar
      tumor palliation. Unilateral biliary drainage may be as effective as bilateral
      drainage for patients with hilar biliary obstruction.

PMID- 23542450
TI  - Glucocorticoids can increase the survival rate of patients with severe viral
      hepatitis B: a meta-analysis.
AB  - OBJECTIVES: Severe viral hepatitis B is a disease associated with significant
      morbidity and mortality. Clinical controlled trials show that the efficacy of
      treatment of severe viral hepatitis B with glucocorticoids remains debatable.
      Therefore, we carried out this meta-analysis to evaluate the safety, efficacy,
      and side effects of glucocorticoid therapy for severe viral hepatitis B. METHODS:
      We searched PubMed, Medline, Embase, Cochrane Library, and Google Scholar for
      randomized-controlled trials published before April 2012 in which glucocorticoid
      therapy was compared with routine treatment for severe viral hepatitis B. The
      primary outcome was the survival rate of the two groups. RESULTS: We selected
      eight controlled clinical trials, which included 597 patients. We recorded a
      benefit of glucocorticoid treatment on the survival rate of patients with severe
      viral hepatitis B (597 patients) [risk ratio (RR)=1.188, 95% confidence interval
      (CI) 1.030-1.369, P=0.018]. The benefit was most noticeable in patients at the
      stage of preliver failure (409 patients) (RR=1.275, 95% CI 1.077-1.510, P=0.005),
      whereas there was no efficacy for patients with liver failure (188 patients)
      (RR=1.008, 95% CI 0.774-1.312, P=0.955). Glucocorticoid treatment was not
      associated with the development of secondary infection and bleeding. CONCLUSION:
      Treatment with glucocorticoids can significantly increase the survival rate of
      patients with severe hepatitis B. The benefit was most noticeable in patients at
      the stage of preliver failure. However, the incidence of secondary infection and
      bleeding did not change significantly. This finding suggests that prompt and
      timely glucocorticoid treatment is crucial.

PMID- 23542451
TI  - Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a
      multiple endocrine neoplasia type 1 family with an uncommon phenotype.
AB  - The objective of this study was to describe a multiple endocrine neoplasia type 1
      (MEN1) family characterized by primary hyperparathyroidism, in association with
      acromegaly because of ectopic growth hormone-releasing hormone (GHRH) secretion
      by a pancreatic neuroendocrine tumor in a young man and with a bronchial
      carcinoid in his mother. We investigate the clinical, radiological imaging,
      histopathologic findings, and therapy. An 18-year-old man successfully underwent
      subtotal parathyroidectomy for primary hyperparathyroidism. A subsequent genetic
      analysis showed a MEN1 gene mutation. Three years later, acromegaly because of
      ectopic GHRH secretion was diagnosed (pituitary MRI negative and elevated GHRH
      levels). A search for an ectopic tumor was unsuccessful and somatostatin analog
      therapy was started. Successively, scintigraphy with somatostatin analogs (68-Ga
      DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal
      pancreatectomy showed multiple pancreatic neuroendocrine tumors and hormonal
      status was normalized. Afterwards, the evaluation of the patient's mother,
      carrying the same mutation, indicated a primary hyperparathyroidism and a 4 cm
      lung mass. The patient underwent subtotal pneumonectomy and the histological
      analysis was consistent with the diagnosis of a typical bronchial carcinoid. In
      conclusion, an atypical phenotype may be recorded in MEN1 families, thus
      emphasizing the importance of the new imaging and surgical techniques in the
      diagnosis and treatment of such a rare disease.

PMID- 23542453
TI  - Genetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited
      neurodegenerative disorders that mainly affect children and are grouped together
      by similar clinical features and the accumulation of autofluorescent storage
      material. More than a dozen genes containing nearly 400 mutations underlying
      human NCLs have been identified. Most of the mutations in these genes are
      associated with a typical disease phenotype, but some result in variable disease
      onset, severity and progression. There are still disease subgroups with unknown
      molecular genetic backgrounds. This article is part of a Special Issue entitled:
      The Neuronal Ceroid Lipofuscinoses or Batten Disease. 

PMID- 23542452
TI  - Benzo[a]pyrene decreases global and gene specific DNA methylation during
      zebrafish development.
AB  - DNA methylation is important for gene regulation and is vulnerable to early-life
      exposure to environmental contaminants. We found that direct waterborne
      benzo[a]pyrene (BaP) exposure at 24MUg/L from 2.5 to 96hpf to zebrafish embryos
      significantly decreased global cytosine methylation by 44.8% and promoter
      methylation in vasa by 17%. Consequently, vasa expression was significantly
      increased by 33%. In contrast, BaP exposure at environmentally relevant
      concentrations did not change CpG island methylation or gene expression in cancer
      genes such as ras-association domain family member 1 (rassf1), telomerase reverse
      transcriptase (tert), c-jun, and c-myca. Similarly, BaP did not change gene
      expression of DNA methyltransferase 1 (dnmt1) and glycine N-methyltransferase
      (gnmt). While total DNMT activity was not affected, GNMT enzyme activity was
      moderately increased. In summary, BaP is an epigenetic modifier for global and
      gene specific DNA methylation status in zebrafish larvae.

PMID- 23542454
TI  - Effect of long-term laboratory propagation on Chlamydia trachomatis genome
      dynamics.
AB  - It is assumed that bacterial strains maintained in the laboratory for long time
      shape their genome in a different fashion from the nature-circulating strains.
      Here, we analyzed the impact of long-term in vitro propagation on the genome of
      the obligate intracellular pathogen Chlamydia trachomatis. We fully-sequenced the
      genome of a historical prototype strain (L2/434/Bu) and a clinical isolate
      (E/CS88), before and after one-year of serial in vitro passaging (up to 3500
      bacterial generations). We observed a slow adaptation of C. trachomatis to the in
      vitro environment, which was essentially governed by four mutations for L2/434/Bu
      and solely one mutation for E/CS88, corresponding to estimated mutation rates
      from 3.84 * 10(-10) to 1.10 * 10(-9) mutations per base pair per generation. In a
      speculative basis, the mutations likely conferred selective advantage as: (i)
      mathematical modeling showed that selective advantage is mandatory for frequency
      increase of a mutated clone; (ii) transversions and non-synonymous mutations were
      overrepresented; (iii) two non-synonymous mutations affected the genes CTL0084
      and CTL0610, encoding a putative transferase and a protein likely implicated in
      transcription regulation respectively, which are families known to be highly
      prone to undergone laboratory-derived advantageous mutations in other bacteria;
      and (iv) the mutation for E/CS88 is located likely in the regulatory region of a
      virulence gene (CT115/incD) believed to play a role in subverting the host cell
      machinery. Nevertheless, we found no significant differences in the growth rate,
      plasmid load, and attachment/entry rate, between strains before and after their
      long-term laboratory propagation. Of note, from the mixture of clones in E/CS88
      initial population, an inactivating mutation in the virulence gene CT135 evolved
      to 100% prevalence, unequivocally indicating that this gene is superfluous for C.
      trachomatis survival in vitro. Globally, C. trachomatis revealed a slow in vitro
      adaptation that only modestly modifies the in vivo-derived genomic evolutionary
      landscape.

PMID- 23542455
TI  - A first insight into the barcodes for African diplostomids (Digenea:
      Diplostomidae): brain parasites in Clarias gariepinus (Siluriformes: Clariidae).
AB  - Diplostomid trematodes comprise a large and diverse group of widespread digeneans
      whose larval stages are important parasitic pathogens that may exert serious
      impacts in wild and cultured freshwater fish. However, our understanding of their
      diversity remains incomplete especially in the tropics. Our study is the first
      application of a DNA-based approach to diplostomid diversity in the African
      continent by generating a database linking sequences for the mitochondrial
      cytochrome c oxidase subunit 1 (cox1) barcode region and ITS1-5.8S-ITS2 rRNA gene
      cluster for brain-infecting diplostomid metacercariae from the catfish Clarias
      gariepinus. Analyses of newly-generated partial cox1 sequences for 34 larval
      isolates of Tylodelphys spp. from Tanzania and Diplostomum spp. from Tanzania and
      Nigeria revealed three strongly supported reciprocally monophyletic lineages of
      Tylodelphys spp. and one of an unknown species of Diplostomum. The average
      intraspecific divergence for the cox1 sequences for each recognised novel lineage
      was distinctly lower compared with interspecific divergence (0.46-0.75% vs 11.7
      14.8%). The phylogenetic hypotheses estimated from Bayesian inference and maximum
      likelihood analyses of ITS1-5.8S-ITS2 data exhibited congruent strong support for
      the cox1-derived lineages. Our study thus provides molecular-based evidence for
      the existence of three distinct brain-infecting species co-occurring in natural
      populations of C. gariepinus. Based on phylogenetic analyses, we re-allocated
      Diplostomum mashonenseBeverley-Burton (1963) to the genus Tylodelphys as a new
      combination. We also generated cox1 and ITS1-5.8S-ITS2 sequences for an unknown
      species of Diplostomum from another African fish host, Synodontis nigrita.

PMID- 23542456
TI  - Prevalence and genetic diversity of piroplasm species in horses and ticks from
      Tunisia.
AB  - The genetic diversity and prevalence of Babesia and Theileria species in the
      equine population of Tunisia were studied using reverse line blot (RLB)
      hybridization on blood samples and unfed adult ticks collected from apparently
      healthy horses from three bioclimatic zones in Tunisia. Piroplasms were
      identified in 13 of 104 of the horse blood samples analyzed (12.5%) and five
      genotype groups were identified: Theileria equi group A (nine animals, 8.7%),
      group C (one animal, 1.0%) and group D (three animals, 2.9%), and Babesia caballi
      groups A and B (one animal each). All horses from the semi-arid zone were
      negative and prevalence in the humid and sub-humid zones were 12.9% and 20.0%,
      respectively. Three Ixodid tick species (Hyalomma marginatum, Hyalomma excavatum
      and Rhipicephalus bursa) were collected from examined horses and equine
      piroplasms were detected in 10.8% of them. T. equi groups A and D (9.2%), and B.
      caballi group B (1.6%) were identified in ticks. This work represents the first
      epidemiological report of equine piroplasmosis in Tunisia. Results showed a high
      level of diversity within the 18S rRNA gene of equine piroplasm species, and
      confirmed the presence in Tunisia of two T. equi genetic groups, C and D, only
      reported before in South Africa and Sudan.

PMID- 23542457
TI  - Epidemiological history and phylogeography of West Nile virus lineage 2.
AB  - West Nile virus (WNV) was first isolated in Uganda. In Europe WNV was
      sporadically detected until 1996, since then the virus has been regularly
      isolated from birds and mosquitoes and caused several outbreaks in horses and
      humans. Phylogenetic analysis showed two main different WNV lineages. The lineage
      1 is widespread and segregates into different subclades (1a-c). WNV-1a includes
      numerous strains from Africa, America, and Eurasia. The spatio-temporal history
      of WNV-1a in Europe was recently described, identifying two main routes of
      dispersion, one in Eastern and the second in Western Europe. The West Nile
      lineage 2 (WNV-2) is mainly present in sub-Saharan Africa but has been recently
      emerged in Eastern and Western European countries. In this study we reconstruct
      the phylogeny of WNV-2 on a spatio-temporal scale in order to estimate the time
      of origin and patterns of geographical dispersal of the different isolates,
      particularly in Europe. Phylogeography findings obtained from E and NS5 gene
      analyses suggest that there were at least two separate introductions of WNV-2
      from the African continent dated back approximately to the year 1999 (Central
      Europe) and 2000 (Russia), respectively. The epidemiological implications and
      clinical consequences of lineage 1 and 2 cocirculation deserve further
      investigations.

PMID- 23542458
TI  - RASSF2 hypermethylation is present and related to shorter survival in squamous
      cervical cancer.
AB  - Ras association (RalGDS/AF-6) domain family member 2 (RASSF2) is a gene involved
      in the progression of several human cancers, including breast, colorectal and
      lung cancer. The aims of this study were to determine the hypermethylation of the
      gene in squamous cervical cancer and precursor lesions, along with that of RASSF1
      and the recently described EPB41L3, and to analyze the potential prognostic role
      of these genes. Methylation-specific PCR and bisulfite sequencing were used to
      analyze the methylation status of RASSF2 and EPB41L3 gene in 60 squamous cervical
      cancer, 76 cervical intraepithelial neoplasias grade III, 16 grade II, 14 grade I
      and 13 cases of normal tissue adjacent to cervical intraepithelial neoplasia.
      RASSF2 expression was evaluated by immunohistochemistry and the re-expression of
      RASSF2 and EPB41L3 was analyzed by quantitative reverse-transcription PCR in
      HeLa, SiHa, C33A and A431 cell lines treated with 5-aza-2'-deoxycytidine and/or
      trichostatin. RASSF1 hypermethylation and human papillomavirus type were also
      analyzed in all the cases by methylation-specific PCR and reverse line blot,
      respectively. RASSF2 hypermethylation was predominant in squamous cervical cancer
      (60.9%) compared with cervical intraepithelial neoplasias (4.2%) and was
      associated with a lower level of RASSF2 expression and vascular invasion in
      squamous cervical cancer. EPB41L3 and RASSF1 hypermethylations were also more
      frequent in cancer than in precursor lesions. Patients with RASSF2
      hypermethylation had shorter survival time, independent of tumor stage (hazard
      ratio: 6.0; 95% confidence interval: 1.5-24.5). Finally, the expressions of
      RASSF2 and EPB41L3 were restored in several cell lines treated with 5-aza-2'
      deoxycytidine. Taken together, our results suggest that RASSF2 potentially
      functions as a new tumor-suppressor gene that is inactivated through
      hypermethylation in cervical cancer and is related to the bad prognosis of these
      patients.

PMID- 23542459
TI  - Early-stage pulmonary adenocarcinoma (T1N0M0): a clinical, radiological,
      surgical, and pathological correlation of 104 cases. The MD Anderson Cancer
      Center Experience.
AB  - The recent proposal for histological subtyping of pulmonary adenocarcinoma by
      predominant pattern and introduction of the terms adenocarcinoma in situ and
      minimally invasive adenocarcinoma to replace the term bronchioloalveolar
      carcinoma by the International Association for the Study of Lung Cancer/American
      Thoracic Society/European Respiratory Society has led us to conduct a study of
      104 patients with early-stage primary pulmonary adenocarcinoma (T1N0M0), with a
      view to histological subtype as defined by the new proposal and clinical outcome.
      None of the clinical parameters of our patient population (type of surgery, age,
      gender, tumor size, and comorbidities) showed any statistically significant
      correlation with outcome, except for associated malignancies, which not
      surprisingly appeared to have a negative impact on survival. In addition,
      statistical analyses of the histological characteristics to include tumor
      differentiation and the percentage of a lepidic or bronchioloalveolar component
      did not show any statistically significant values in terms of survival. Our
      results failed to show any statistically significant difference of survival
      between those T1N0M0 adenocarcinomas with a lepidic component and those without,
      thus questioning the use of terms such as in situ or minimally invasive
      adenocarcinoma. On the basis of our results, we consider that the outcome for
      patients with T1N0M0 disease is still best determined by appropriate staging
      rather than by changes in the pathology nomenclature of adenocarcinoma.

PMID- 23542460
TI  - Arsenate accumulation and arsenate-induced glutathione export in astrocyte-rich
      primary cultures.
AB  - Arsenate is a toxic compound that has been connected with neuropathies and
      impaired cognitive functions. To test whether arsenate affects the viability and
      the GSH metabolism of brain astrocytes, we have used primary astrocyte cultures
      as model system. Incubation of astrocytes for 2h with arsenate in concentrations
      of up to 10mM caused an almost linear increase in the cellular arsenic content,
      but did not acutely compromise cell viability. The presence of moderate
      concentrations of arsenate caused a time- and concentration-dependent loss of GSH
      from viable astrocytes which was accompanied by a matching increase in the
      extracellular GSH content. Half-maximal effects were observed for arsenate in a
      concentration of about 0.3 mM. The arsenate-induced stimulated GSH export from
      astrocytes was prevented by MK571, an inhibitor of the multidrug resistance
      protein 1. Exposure of astrocytes to arsenite increased the specific cellular
      arsenic content and stimulated GSH export to values that were similar to those
      observed for arsenate-treated cells, while dimethylarsinic acid was less
      efficiently accumulated by the cells and did not modulate cellular and
      extracellular GSH levels. The observed strong stimulation of GSH export from
      astrocytes by arsenate suggests that disturbances of the astrocytic GSH
      metabolism may contribute to the observed arsenic-induced neurotoxicity.

PMID- 23542461
TI  - Prevalence of Haemoproteus columbae and Trichomonas gallinae in pigeons (Columba
      domestica) in Isfahan, Iran.
AB  - The aim of this study was to determine the prevalence of Haemoproteus columbae
      and Trichomonas gallinae in pigeons (Columba domestica) in Isfahan, Iran. Study
      was done on 100 pigeons from January to June 2010 in Isfahan located in south of
      Iran. Oropharyngeal swabs were taken from all birds. Also blood samples were
      obtained from wing vein and thin smears were prepared from them. All smears were
      stained by Giemsa and were examined by immersion. Out of 100 Oropharyngeal swab
      smears 57 (57%) were positive for T. gallinae and Haemoproteus gallinae were
      detected in 62 pigeons (62%) from which blood smear were taken. The present study
      is in close agreement with other studies in Iran. But infestation rate to theses
      parasite in world are very different. These differences were probably linked to
      geographical variations and differences in the feeding habitat and abundance of
      vehicles of Haemoproteus.

PMID- 23542462
TI  - Airway clearance research in CF: the 'perfect storm' of strong preference and
      effortful participation in long-term, non-blinded studies.

PMID- 23542463
TI  - Pulmonary exacerbations as indicators of progression of lung disease in young
      children with CF.

PMID- 23542464
TI  - AMP deaminase 3 plays a critical role in remote reperfusion lung injury.
AB  - Remote reperfusion lung injury following skeletal muscle ischemia and reperfusion
      accounts for high morbidity and mortality. AMP deaminase (AMPD), a key enzyme for
      nucleotide cycle, has been implicated in the regulation of this phenomenon.
      However, the function of Ampd2 and Ampd3 subtype has not been elucidated in
      remote reperfusion rodent lung injury. We utilized AMPD3 and AMPD2-deficient
      mice. The two types of AMPD-deficient mice and wild-type (WT) littermates were
      subjected to ischemia-reperfusion injury. After 3h bilateral hind-limb ischemia
      and reperfusion, AMPD3 mRNA, AMPD activity and inosine monophosphate (IMP)
      increased significantly in WT and AMPD2-deficient mice lungs, while they did not
      show significant alterations in AMPD3-deficient mice lungs. Genetic inactivation
      of Ampd3 resulted in markedly accelerated myeloperoxidase (MPO) activity along
      with exaggerated neutrophils infiltration and hemorrhage in the lungs compared to
      WT and AMPD2-deficient mice, furthermore, IMP treatment significantly attenuated
      MPO activity and neutrophils infiltration in WT and the two types of AMPD
      deficient mice lungs after 3h reperfusion. These findings demonstrate for the
      first time in AMP-deficient mice models that AMPD3 plays a critical role in
      remote reperfusion lung injury via generation of IMP and validate the potential
      to use IMP into the clinical arena to attenuate remote ischemia-reperfusion lung
      injury.

PMID- 23542465
TI  - Tet1 is required for Rb phosphorylation during G1/S phase transition.
AB  - DNA methylation plays an important role in many biological processes, including
      regulation of gene expression, maintenance of chromatin conformation and genomic
      stability. TET-family proteins convert 5-methylcytosine (5mC) to 5
      hydroxymethylcytosine (5hmC), which indicates that these enzymes may participate
      in DNA demethylation. The function of TET1 has not yet been well characterized in
      somatic cells. Here, we show that depletion of Tet1 in NIH3T3 cells inhibits cell
      growth. Furthermore, Tet1 knockdown blocks cyclin D1 accumulation in G1 phase,
      inhibits Rb phosphorylation and consequently delays entrance to G1/S phase. Taken
      together, this study demonstrates that Tet1 is required for cell proliferation
      and that this process is mediated through the Rb pathway.

PMID- 23542466
TI  - Quantitative proteomics of auditory fear conditioning.
AB  - Auditory fear conditioning is a well-characterized rodent learning model where a
      neutral auditory cue is paired with an aversive outcome to induce associative
      fear memory. The storage of long-term auditory fear memory requires long-term
      potentiation (LTP) in the lateral amygdala and de novo protein synthesis.
      Although many studies focused on individual proteins have shown their
      contribution to LTP and fear conditioning, non-biased genome-wide studies have
      only recently been possible with microarrays, which nevertheless fall short of
      measuring changes at the level of proteins. Here we employed quantitative
      proteomics to examine the expression of hundreds of proteins in the lateral
      amygdala in response to auditory fear conditioning. We found that various
      proteins previously implicated in LTP, learning and axon/dendrite growth were
      regulated by fear conditioning. A substantial number of proteins that were
      regulated by fear conditioning have not yet been studied specifically in learning
      or synaptic plasticity.

PMID- 23542467
TI  - HER2 mediates epidermal growth factor-induced down-regulation of E-cadherin in
      human ovarian cancer cells.
AB  - Overexpression of HER2 is correlated with a poor prognosis in many types of human
      cancers. Due to the interaction between HER2 and other ErbB receptors, HER2 is
      implicated in the EGF family of ligands-regulated tumor progression. In ovarian
      cancer, although the relationships between HER2 amplification and patient
      prognosis remain controversial, the underlying molecular mechanisms of HER2
      mediated tumor progression are not fully understood. Our previous studies
      demonstrated that EGF induces ovarian cancer cell invasion by down-regulating E
      cadherin expression through the up-regulation of its transcriptional repressors,
      Snail and Slug. It has been shown that overexpression of HER2 down-regulates E
      cadherin expression in human mammary epithelial cells. However, whether HER2
      mediates EGF-induced down-regulation of E-cadherin remains unknown. In this
      study, we examined the potential role of HER2 in EGF-induced down-regulation of E
      cadherin and increased cell invasion. We show that EGF treatment induces the
      interaction of EGFR with HER2 and increases the activation of HER2 in human
      ovarian cancer cells; we also show that these effects are diminished by knockdown
      of EGFR. Importantly, treatment with HER2-specific tyrosine kinase inhibitor,
      AG825, and HER2 siRNA diminished the up-regulation of Snail and Slug as well as
      the down-regulation of E-cadherin by EGF. Finally, we also show that EGF-induced
      cell invasion was attenuated by treatment with HER2 siRNA. This study
      demonstrates an important role for HER2 in mediating the effects of EGF on Snail,
      Slug and E-cadherin expression as well as invasiveness in human ovarian cancer
      cells.

PMID- 23542468
TI  - Transnasal skull base reconstruction using a 3-d endoscope: our first
      impressions.
AB  - Nowadays endoscopic skull base reconstruction is safely and effectively performed
      by means of two-dimensional (2-D) endoscopic technique. The aim of our study is
      to compare our 2-D experience with the novel 3-D technology in the field of skull
      base reconstruction techniques. In this study four patients treated with various
      kinds of planned duraplasty are included. The new 3-D technology was compared
      with the high-definition 2-D scopes during the different steps of the procedures.
      The 3-D endoscopic skull base reconstruction obtained primary closure without
      complications in all cases. According to the subjective opinion of experienced
      endosurgeons, this novel technique improved depth perception, distance and size
      estimation, ability to identify specific anatomic structures, and hand-eye
      coordination. The main drawbacks detected were inferior sharpness, contrast and
      lighting that impaired the application of the technique in narrow sinonasal
      spaces. According to our preliminary impressions, 3-D endoscopic skull base
      reconstruction is an effective and safe procedure and could represent a
      significant advantage for accurate managing of the skull base region.

PMID- 23542469
TI  - Once-daily extended-release versus twice-daily standard-release tacrolimus in
      kidney transplant recipients: a systematic review.
AB  - BACKGROUND: A simplified dosing regimen may improve drug compliance in kidney
      transplant recipients and long-term graft outcomes. We aimed to identify,
      appraise, and synthesize the current evidence comparing the relative safety and
      efficacy of the recently introduced daily versus standard twice-daily tacrolimus
      administration. METHODS: We systematically reviewed all randomized controlled
      trials and observational studies that compared the outcomes of daily versus twice
      daily tacrolimus formulation in kidney transplant recipients. Medline (from 1948
      to July week 4 2011), Embase (1980 to 2011 week 31), the Cochrane Library (1991
      to June 2011), and conference proceedings were searched without language
      restriction. RESULTS: Six randomized controlled trials (n=2499) and 15
      observational studies (n=2886) were included in the review. There were no
      significant differences in biopsy-proven acute rejection (two trials, n=1093;
      risk ratio [RR; confidence interval (CI)], 1.24 [0.93-1.65]; P=0.15; I=0%),
      patient survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.55;
      I=32%), and graft survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02];
      P=0.67; I=0%) between the two formulations at 12 months. Similar results for
      acute rejection (five studies, n=391; RR [CI], 0.99 [0.93-1.06]; P=0.84; I=0%)
      and overall patient survival (two studies, n=218; RR [CI], 1.02 [0.94-1.10];
      P=0.62; I=0%) were observed in observational studies. CONCLUSIONS: Once-daily
      tacrolimus appears to be as effective as twice-daily tacrolimus up to 12 months
      after kidney transplantation.

PMID- 23542470
TI  - Significance of true-positive and false-positive pretransplantation
      lymphocytotoxic crossmatch in primary liver allograft outcomes.
AB  - BACKGROUND: At the time of transplantation, a recipient's serum is tested against
      the prospective donor's lymphocytes to identify specific reactivity and to look
      for a donor-specific crossmatch (CXM). Here, we investigated the relationship
      between the pretransplantation lymphocytotoxic CXM results and the long-term
      outcome of liver transplantation at a single center. METHODS: From October 1998
      to April 2011, medical records, laboratory data, and pretransplantation
      lymphocytotoxic CXM results were collected from 1133 consecutive liver transplant
      recipients. RESULTS: We performed liver transplantations on 80 (7.1%) patients
      after a true-positive CXM (t+CXM). The t+CXM group exhibited higher initial
      aminotransferase levels immediately after transplantation compared with a
      negative CXM group. However, no significant differences in rejection, biliary or
      vascular complications, viral disease recurrence, or de novo malignancies were
      found. Although overall graft and patient survival did not differ between the
      groups, liver-specific graft survival was inferior in the t+CXM group. It was
      also found that, in 42 (3.7%) recipients, initially positive results converted to
      final negative results after the elimination of immunoglobulin M autoantibodies.
      We defined this subpopulation as a false-positive CXM. Significantly decreased
      posttransplantation aminotransferase levels with a higher incidence of de novo
      malignancies were observed in this group compared with negative controls.
      CONCLUSION: Our findings demonstrate that t+CXM transplants show increased
      aspartate aminotransferase and alanine aminotransferase peak immediately after
      transplantation, which influences liver-specific graft outcomes. Additionally,
      the presence of circulating immunoglobulin M autoantibodies against recipients'
      own antigens may be protective in liver grafts. However, this may be a
      predisposing factor for de novo malignancies.

PMID- 23542471
TI  - Psychologic functioning of unspecified anonymous living kidney donors before and
      after donation.
AB  - BACKGROUND: There has been discussion regarding the psychologic functioning of
      living donors who donate their kidney to an unrelated and unknown patient
      ("unspecified living donors"). This is the first prospective study to investigate
      group- and individual-level changes in psychologic functioning among a large
      group of unspecified donors. METHODS: Forty-nine medically and psychologically
      screened unspecified living kidney donors completed the Symptom Checklist before
      and after donation. RESULTS: Group-level analysis showed that overall psychologic
      symptoms increased after donation (P=0.007); the means remained within the
      average range of the normal population. Individual-level analysis showed that 33
      donors showed no statistically significant change, 3 donors showed a
      statistically significant decrease, and 13 donors showed a statistically
      significant increase in psychologic symptoms. Two of the latter donors showed a
      clinically significant increase. CONCLUSIONS: We found more increases in
      psychologic symptoms than decreases, particularly if follow-up time was longer.
      However, for almost all donors, these increases were not clinically significant
      and the clinically significant changes found are comparable with natural
      fluctuations in psychologic symptoms in the general population. Possibly, the
      donors underreported their psychologic symptoms before donation to pass the
      screening. Due to the low level of predonation symptoms reported, regression to
      the mean could also explain the results. Although we found that changes were not
      associated with donation-related factors, it is possible that other donation
      related factors or other life events not measured have an influence on
      psychologic functioning. Therefore, further research is needed to investigate
      whether the fluctuations are related to the donation process.

PMID- 23542472
TI  - Steatosis among living liver donors without evidence of fatty liver on
      ultrasonography: potential implications for preoperative liver biopsy.
AB  - BACKGROUND: The degree of steatosis is an important factor that determines the
      graft function in the recipient and the recovery of the remnant liver in the
      living donor. To date, there is no consensus regarding how to assess steatosis
      among potential living liver donors. We evaluate the prevalence and risk factors
      for steatosis in living liver donors with normal serum aminotransferase levels
      and without fatty liver on ultrasonography (US-negative). METHODS: The degree of
      steatosis was assessed for a total of 492 US-negative living liver donors with
      normal aminotransferase levels (age 30.1+/-9.9; male 301 [61.2%]). Total
      steatosis was defined by adding the degree of macrosteatosis and microsteatosis.
      RESULTS: No liver donor had a severe degree (>=60%) of macrosteatosis or
      microsteatosis. A moderate degree (30-59%) of macrosteatosis and microsteatosis
      was seen in 4 (0.8%) and 26 (5.3%) subjects, respectively. Severe and moderate
      degrees of total steatosis were seen in 3 (0.6%) and 53 (10.8%) subjects,
      respectively. Body mass index and serum triglyceride levels were independent
      factors associated with the moderate or greater degree of total steatosis.
      CONCLUSIONS: Noninvasive preoperative assessment for liver steatosis (US-negative
      with normal aminotransferase level) was sufficient to exclude severe
      macrosteatosis or microsteatosis and moderate macrosteatosis but not sufficient
      to exclude moderate microsteatosis or total steatosis in living liver donors.

PMID- 23542473
TI  - Do echocardiographic parameters predict mortality in patients with end-stage
      renal disease?
AB  - BACKGROUND: Left ventricular function predicts cardiovascular mortality both in
      the general population and those with end-stage renal disease. Echocardiography
      is commonly undertaken as a screening test before kidney transplantation;
      however, there are little data on its predictive power. METHODS: This was a
      retrospective review of patients assessed for renal transplantation from 2000 to
      2009. A survival analysis using demographic and echocardiographic variables was
      undertaken using the Cox proportional hazards regression model. RESULTS: Of 862
      patients assessed for transplantation, 739 had an echocardiogram and 217 of 739
      (29%) died during a mean follow-up of 4.2 years. In a multivariate survival
      analysis, increased age (P<0.0001), diabetes (P<0.0001), transplant listing
      status (P<0.0001), severely impaired left ventricular function (P<0.01),
      pulmonary hypertension and/or right ventricular dysfunction (P=0.01), and
      regional wall motion abnormalities (P<0.01) were associated with all-cause
      mortality. Combined in a score where one point was given for the presence of each
      of the parameters above, these factors were strongly predictive of increased
      mortality with a hazard ratio of 3.57, 6.80, and 44.47 for the presence of one,
      two, or more factors, respectively, compared with the absence of any of these
      factors. CONCLUSIONS: In patients with end-stage renal disease, multiple easily
      determined echocardiographic parameters, including regional wall motion
      abnormalities and pulmonary hypertension and/or right ventricular dysfunction,
      were independently associated with all-cause and cardiovascular mortality.
      Combining these factors in a simple score may further assist in risk stratifying
      patients being considered for renal transplantation.

PMID- 23542474
TI  - The differential tissue expression of inflammatory, oxidative stress, and
      apoptosis markers in human uncontrolled non-heart-beating donors.
AB  - BACKGROUND: Uncontrolled non-heart-beating donor (UNHBD) transplantation offers a
      major opportunity to ameliorate the effects of the donor shortage. However,
      little is known about the true status of the organs obtained from these donors.
      UNHBD transplantation is performed under unfavorable conditions and involves
      exposure to several harmful stimuli that have been identified as triggers for
      immediate inflammatory response, oxidative stress, and apoptotic phenomena. This
      adverse scenario could explain the higher rates of graft dysfunction due to
      primary nonfunction traditionally observed in NHBD. Our aim was to assess the
      expression of proinflammatory, oxidative, and apoptotic markers in liver, lung,
      and pancreas tissue samples obtained from UNHBD and to compare these expression
      levels with those observed in brain-dead donors (BDD). METHODS: Samples from
      human type 2 NHBD and BDD were obtained at the end of cold storage. Interleukin
      (IL)-1beta, tumor necrosis factor-alpha, IL-6, IL-10, endothelial nitric oxide
      synthase, inducible nitric oxide synthase, type 1 heme oxygenase, type 2 heme
      oxygenase, Bax, and Bcl-2 protein and mRNA expression, as well as catalase,
      glutathione peroxidase, and glutathione reductase tissue activity, were
      determined. RESULTS: UNHBD showed similar or lower expression of proinflammatory
      mediators and apoptosis markers in all three organs without modifications to the
      anti-inflammatory cytokines. Although the major oxidative stress marker levels
      were also comparable in both types of donors, the type 1 heme oxygenase mRNA
      expression and antioxidant enzyme activity were slightly diminished in UNHBD.
      CONCLUSIONS: The initial tissue damage generated during the UNHB donation process
      is at least comparable with that observed in BDD. However, although the
      expression of the immediate immune response and apoptosis markers is similar, a
      mild impairment of the local antioxidant activity was observed.

PMID- 23542475
TI  - A prevalence of thyroid disorder in Western part of Nepal.
AB  - BACKGROUND: Nepal is an endemic area with regards to iodine deficiency, as well
      as a nutritional iodine deficiency is thought to be prevalent in all the
      Himalayan, sub-Himalayan and the Terai regions of Nepal. Thyroid dysfunction is a
      major public health problem among the Nepalese population. OBJECTIVES: The
      objective of this study was to find out the prevalence of thyroid dysfunction
      among the patients who attended the Charak Hospital, Pokhara, Nepal. MATERIALS
      AND METHODS: A hospital based study was undertaken by using the data which was
      retrieved from the thyroid function tests, which included free T3, free T4 and
      TSH, from the register which was maintained in the Department of Biochemistry of
      the Charak Hospital, Pokhara, Nepal, from 1(st) January, 2011 to 30th December,
      2012. Descriptive statistics and testing of the hypothesis were used for the
      analysis by using the EPI INFO and the SPSS version 16 softwares. RESULTS: The
      total number of cases was 1504, which included 23.20% males and 76.80% females.
      The prevalence of thyroid dysfunction was 17.42%. Females had more thyroid
      dysfunction than the males. Hypothyroidism (2.26%) and subclinical hypothyroidism
      (10.50%) had higher prevalences as compared to hyperthyroidism (1.59%) and
      subclinical hyperthyroidism (3.05%) in the western region of Nepal. A higher
      prevalence of the thyroid dysfunction was observed in the subjects who ages were
      above 41-50 years. CONCLUSION: Females and people of advanced ages were more
      vulnerable to thyroid dysfunction in the population. Hypothyroidism and
      subclinical hypothyroidism were preponderant, followed by subclinical
      hyperthyroidism.

PMID- 23542477
TI  - Development and application of a quantitative PCR assay targeting Catellicoccus
      marimammalium for assessing gull-associated fecal contamination at Lake Erie
      beaches.
AB  - Gulls represent one of the major fecal contamination sources responsible for the
      degradation of water quality at Lake Erie beaches. For assessing gull-associated
      fecal contamination, a real-time quantitative PCR assay (qPCR) targeting 16S rRNA
      gene sequences from Catellicoccus marimammalium, which are abundant in gull
      feces, was developed and evaluated by comparing assay results with beach survey
      data that included gull counting, and quantifying densities of Escherichia coli
      and human-associated fecal markers at two Lake Erie beaches. In evaluating the
      specificity and sensitivity of the qPCR assay with animal and wastewater samples,
      C. marimammalium was detected in most gull fecal samples (80.7%), some chicken
      fecal samples (24.1%), but was not readily detected from other fecal samples of
      animals and humans, and wastewater. Among 66 Lake Erie water samples collected in
      2010, C. marimammalium was frequently detected from Villa Angela (36.4%) and
      Headlands beaches (57.6%). C. marimammalium densities were not associated with E.
      coli densities or sanitary survey data. E. coli counts were likely driven by
      other sources, such as human, rather than gulls at the study sites. The
      presumption that human contamination influenced E. coli counts was supported by
      more frequent detection of the human-specific Bacteroides gyrB marker (gyrB) at
      Villa Angela (33.3%) than Headlands (6.1%). Since E. coli may not be an effective
      indicator for assessing gull-related fecal contamination at these beaches, where
      contamination sources are mixed, our novel qPCR assay can be useful for
      understanding fecal source contributions from gulls not explained by gull
      abundance or E. coli densities.

PMID- 23542478
TI  - Multivariate study of trace element distribution in the geological record of
      Ronanzas Peat Bog (Asturias, N. Spain). Paleoenvironmental evolution and human
      activities over the last 8000 calyr BP.
AB  - Trace element concentrations in the Ronanzas peat bog record reveal a
      contribution of natural processes but the influence of anthropogenic factors
      predominates in the last two millenniums, particularly aerosol deposition linked
      to mining and industrial activities in northern Spain. We observed that the
      Ronanzas record can be considered a preserved environment, suitable to search for
      local (<50 km), regional (50-150 km) and/or long-distance human activity
      fingerprinting, specifically that related to the deposition of heavy metals such
      as Pb, Zn and Hg. We also carried out a multivariate statistical study in order
      to clarify the geochemical behavior of trace and major elements. Our study design
      represents a novel approach to assign natural vs. human contributions in
      peatlands. Therefore, synergies obtained by the simultaneous study of
      multivariate statistics and enrichment factors allow robust conclusions about
      paleoenvironmental evolution and human activities. Anthropogenic influence has
      also been reported in similar records in other parts of Europe, thereby
      suggesting large-scale sources for atmospheric pollution. However, here we
      revealed remarkable particularities, such as the association of Cd, Zn and Pb,
      mainly linked to regional and local factors (mining and more recently the
      metallurgical industry), whereas we propose that the occurrence of Hg is
      associated with a combination of regional factors and global atmospheric
      pollution.

PMID- 23542479
TI  - Comparing fuel reduction treatments for reducing wildfire size and intensity in a
      boreal forest landscape of northeastern China.
AB  - Fuel load is often used to prioritize stands for fuel reduction treatments.
      However, wildfire size and intensity are not only related to fuel loads but also
      to a wide range of other spatially related factors such as topography, weather
      and human activity. In prioritizing fuel reduction treatments, we propose using
      burn probability to account for the effects of spatially related factors that can
      affect wildfire size and intensity. Our burn probability incorporated fuel load,
      ignition probability, and spread probability (spatial controls to wildfire) at a
      particular location across a landscape. Our goal was to assess differences in
      reducing wildfire size and intensity using fuel-load and burn-probability based
      treatment prioritization approaches. Our study was conducted in a boreal forest
      in northeastern China. We derived a fuel load map from a stand map and a burn
      probability map based on historical fire records and potential wildfire spread
      pattern. The burn probability map was validated using historical records of
      burned patches. We then simulated 100 ignitions and six fuel reduction treatments
      to compare fire size and intensity under two approaches of fuel treatment
      prioritization. We calibrated and validated simulated wildfires against
      historical wildfire data. Our results showed that fuel reduction treatments based
      on burn probability were more effective at reducing simulated wildfire size, mean
      and maximum rate of spread, and mean fire intensity, but less effective at
      reducing maximum fire intensity across the burned landscape than treatments based
      on fuel load. Thus, contributions from both fuels and spatially related factors
      should be considered for each fuel reduction treatment.

PMID- 23542480
TI  - Pressures at larger spatial scales strongly influence the ecological status of
      heavily modified river water bodies in Germany.
AB  - River biota are influenced by anthropogenic pressures that operate at different
      spatial scales. Understanding which pressures at which spatial scales affect
      biota is essential to manage and restore degraded rivers. In Europe, many river
      reaches were designated as Heavily Modified Water Bodies (HMWB) according to the
      European Water Framework Directive (WFD), where the ecological potential might
      mainly be determined by pressures at larger spatial scales outside the HMWB (e.g.
      hydromorphological alterations at the river network and land use at the catchment
      scale). In Germany, hydromorphological alterations and diffuse pollution were the
      main pressures. Therefore, the three objectives of this study were to (i)
      identify the hydromorphological pressures at the site, reach, and river network
      scale, and land use categories at the catchment scale which significantly affect
      the ecological status of HMWB in Germany, (ii) quantify the relative importance
      of these pressures at different spatial scales, and (iii) analyse the differences
      in response between fish and macroinvertebrates. The results indicated that: (i)
      At the reach scale, fish were most strongly influenced by channel-bank conditions
      whilst the naturalness of channel-planform was the best proxy for the ecological
      status of macroinvertebrates. At the catchment scale, urbanization was the most
      detrimental land use. (ii) The pressures at larger spatial scales (catchment land
      use and hydromorphological alterations in the river network) generally were more
      important than hydromorphological alterations at the reach scale. (iii) Fish were
      affected equally by both, hydromorphological alterations at the reach scale and
      large-scale pressures whereas the latter were far more important for the
      ecological status of macroinvertebrates. In conclusion, these results indicated
      that large-scale pressures may often limit the efficiency of reach-scale
      restoration, especially for macroinvertebrates, even in the absence of saprobic
      pollution, and have to be considered for the management and restoration of HMWB
      in Germany and comparable degraded river reaches.

PMID- 23542481
TI  - Fine particulate matter in the indoor air of barbeque restaurants: elemental
      compositions, sources and health risks.
AB  - Cooking is a significant source of indoor particulate matter that can cause
      adverse health effects. In this study, a 5-stage cascade impactor was used to
      collect particulate matter from 14 restaurants that cooked with charcoal in
      Kocaeli, the second largest city in Turkey. A total of 24 elements were
      quantified using ICP-MS. All of the element contents except for Mn were higher
      for fine particles (PM2.5) than coarse particles (PM>2.5), and the major trace
      elements identified in the PM2.5 included V, Se, Zn, Cr, As, Cu, Ni, and Pb.
      Principle component analysis (PCA) and enrichment factor (EF) calculations were
      used to determine the sources of PM2.5. Four factors that explained over 77% of
      the total variance were identified by the PCA. These factors included charcoal
      combustion, indoor activities, crustal components, and road dust. The Se, As, Cd,
      and V contents in the PM2.5 were highly enriched (EF>100). The health risks posed
      by the individual metals were calculated to assess the potential health risks
      associated with inhaling the fine particles released during charcoal cooking. The
      total hazard quotient (total HQ) for a PM2.5 of 4.09 was four times greater than
      the acceptable limit (i.e., 1.0). In addition, the excess lifetime cancer risk
      (total ELCR) for PM2.5 was 1.57*10(-4), which is higher than the acceptable limit
      of 1.0*10(-6). Among all of the carcinogenic elements present in the PM2.5, the
      cancer risks resulting from Cr(VI) and As exposure were the highest (i.e.,
      1.16*10(-4) and 3.89*10(-5), respectively). Overall, these results indicate that
      the lifetime cancer risk associated with As and Cr(VI) exposure is significant at
      selected restaurants, which is of concern for restaurant workers.

PMID- 23542483
TI  - Source apportionment of PM10, organic carbon and elemental carbon at Swiss sites:
      an intercomparison of different approaches.
AB  - In this study, the results of source apportionment of particulate matter (PM10),
      organic carbon (OC), and elemental carbon (EC) - as obtained through different
      approaches at different types of sites (urban background, urban roadside, and two
      rural sites in Switzerland) - are compared. The methods included in this
      intercomparison are positive matrix factorisation modelling (PMF, applied to
      chemical composition data including trace elements, inorganic ions, OC, and EC),
      molecular marker chemical mass balance modelling (MM-CMB), and the aethalometer
      model (AeM). At all sites, the agreement of the obtained source contributions was
      reasonable for OC, EC, and PM10. Based on an annual average, and at most of the
      considered sites, secondary organic carbon (SOC) is the component with the
      largest contribution to total OC; the most important primary source of OC is wood
      combustion, followed by road traffic. Secondary aerosols predominate in PM10. All
      considered techniques identified road traffic as the dominant source of EC, while
      wood combustion emissions are of minor importance for this constituent. The
      intercomparison of different source apportionment approaches is helpful to
      identify the strengths and the weaknesses of the different methods. Application
      of PMF has limitations when source emissions have a strong temporal correlation,
      or when meteorology has a strong impact on PM variability. In these cases, the
      use of PMF can result in mixed source profiles and consequently in the under- or
      overestimation of the real-world sources. The application of CMB models can be
      hampered by the unavailability of source profiles and the non-representativeness
      of the available profiles for local source emissions. This study also underlines
      that chemical transformations of molecular markers in the atmosphere can lead to
      the underestimation of contributions from primary sources, in particular during
      the summer period or when emission sources are far away from the receptor sites.

PMID- 23542482
TI  - Modelling temperature effects on ammonia-oxidising bacterial biostability in
      chloraminated systems.
AB  - The biostability concept has been successfully used to predict the onset of
      nitrification in drinking water distribution systems, but in certain cases
      deficiencies have been observed in the predictions, indicating that modifications
      to parameters were needed. At the biostable disinfectant residual concentration
      (BRC), the rate of ammonia-oxidising bacterial (AOB) growth due to the substrate
      (free ammonia) and the rate of inactivation due to the disinfectant are balanced.
      Growth and inactivation rates vary greatly with temperature, but temperature is
      yet to be considered in the biostability equation. In this paper, two separate
      novel models are proposed which take into account the temperature effects on the
      biostability equation. First, a novel model of specific growth rate variability
      with temperature was shown to be valid for different bacterial species. Then, the
      biostability model was modified and validated for ammonia-oxidising bacterial
      activity using data collected from laboratory and full-scale distribution
      systems. The proposed model has two important uses: while the specific growth
      rate model and biostability model can be widely adopted for many microbes, the
      biostability model for AOB also has the potential to aid water utilities in
      disinfectant residual management throughout yearly temperature variations.

PMID- 23542484
TI  - The occurrence and distribution of a group of organic micropollutants in Mexico
      City's water sources.
AB  - The occurrence and distribution of a group of 17 organic micropollutants in
      surface and groundwater sources from Mexico City was determined. Water samples
      were taken from 7 wells, 4 dams and 15 tanks where surface and groundwater are
      mixed and stored before distribution. Results evidenced the occurrence of seven
      of the target compounds in groundwater: salicylic acid, diclofenac, di-2
      ethylhexylphthalate (DEHP), butylbenzylphthalate (BBP), triclosan, bisphenol A
      (BPA) and 4-nonylphenol (4-NP). In surface water, 11 target pollutants were
      detected: same found in groundwater as well as naproxen, ibuprofen, ketoprofen
      and gemfibrozil. In groundwater, concentration ranges of salicylic acid, 4-NP and
      DEHP, the most frequently found compounds, were 1-464, 1-47 and 19-232 ng/L,
      respectively; while in surface water, these ranges were 29-309, 89-655 and 75
      2,282 ng/L, respectively. Eleven target compounds were detected in mixed water.
      Concentrations in mixed water were higher than those determined in groundwater
      but lower than the detected in surface water. Different to that found in ground
      and surface water, the pesticide 2,4-D was found in mixed water, indicating that
      some pollutants can reach areas where they are not originally present in the
      local water sources. Concentration of the organic micropollutants found in this
      study showed similar to lower to those reported in water sources from developed
      countries. This study provides information that enriches the state of the art on
      the occurrence of organic micropollutants in water sources worldwide, notably in
      megacities of developing countries.

PMID- 23542485
TI  - Effect of monovalent and divalent cations, anions and fulvic acid on aggregation
      of citrate-coated silver nanoparticles.
AB  - The dynamic nature of nanoparticle (NP) aggregation behavior is of paramount
      interest to many current studies in environmental and toxicological nanoscience.
      The present study seeks to elucidate the influence that different electrolytes
      have on the aggregation of citrate-coated silver NPs (cit-AgNPs). The use of both
      UV-vis spectroscopy and dynamic light scattering (DLS, both z-average
      hydrodynamic diameter (z-dh) and size distribution analysis data) allowed
      improvement in the data quality and interpretation as compared to other studies
      using only DLS and reporting solely the z-dh, as the change in the z-dh can be
      related to analytical errors and uncertainties rather than only aggregation or
      dissolution of NPs. Divalent cations (CaCl2, Ca(NO3)2, CaSO4, MgCl2 and MgSO4)
      have stronger influence (ca. 50-65 fold) on aggregation of cit-AgNPs as compared
      to monovalent cations (NaCl, NaNO3, Na2SO4), as expected. For electrolytes with
      monovalent cations, there was no specific ion effect of nitrate and sulfate
      anions. However, the addition of chloride anions resulted in enhanced apparent
      aggregation, possibly due to the formation of AgCl NPs that sorb/attach to the
      surface of cit-AgNPs. Suwannee River fulvic acid enhances the stability of cit
      AgNPs and shifts the critical coagulation concentrations to higher electrolyte
      concentrations for all types of electrolytes. Aggregation kinetics in the
      presence of mixture of monovalent and divalent cations is additive and controlled
      by the dominant cations. An empirical formula (alphamixture=alphaNa+(50 to 65)Ca)
      is proposed that reproduces the effect of mixtures of electrolytes in the
      presence of humic substances and cations that can be used to help predict the
      aggregation behavior of cit-AgNPs in environmental and ecotoxicological media.

PMID- 23542486
TI  - A multi-assay screening approach for assessment of endocrine-active contaminants
      in wastewater effluent samples.
AB  - Environmental agencies must monitor an ever increasing range of contaminants of
      emerging concern, including endocrine disrupting compounds (EDCs). An alternative
      to using ultra-trace chemical analysis of samples for EDCs is to test for
      biological activity using in vitro screening assays, then use these assay results
      to direct analytical chemistry approaches. In this study, we used both analytical
      approaches and in vitro bioassays to characterize the EDCs present in treated
      wastewater from four wastewater treatment plants (WWTPs) in Ontario, Canada.
      Estrogen-mediated activity was assessed using a yeast estrogenicity screening
      (YES) assay. An in vitro competitive binding assay was used to assess capacity to
      interfere with binding of the thyroid hormone, thyroxine (T4) to the recombinant
      human thyroid hormone transport protein, transthyretin (i.e. hTTR). An in vitro
      binding assay with a rat peroxisome proliferator responsive element transfected
      into a rainbow trout gill cell line was used to evaluate binding and subsequent
      gene expression via the peroxisome proliferator activated receptor (PPAR).
      Analyses of a suite of contaminants known to be EDCs in extracts from treated
      wastewater were conducted using either gas chromatography with mass spectrometry
      (GC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS/MS).
      Estrogenic activity was detected in the YES assay only in those extracts that
      contained detectable amounts of estradiol (E2). There was a positive relationship
      between the degree of response in the T4-hTTR assay and the amounts of
      polybrominated diphenyl ether (PBDE) congeners 47 and 99, triclosan and the PBDE
      metabolite, 4-OH-BDE17. Several wastewater extracts gave a positive response in
      the PPAR assay, but these responses were not correlated with the amounts of any
      of the EDCs analyzed by LC-MS/MS. Overall, these data indicate that a step-wise
      approach is feasible using a combination of in vitro testing and instrumental
      analysis to monitor for EDCs in wastewater and other environmental matrixes.

PMID- 23542487
TI  - Penguins as bioindicators of mercury contamination in the Southern Ocean: birds
      from the Kerguelen Islands as a case study.
AB  - Seabirds have been used extensively as bioindicators of mercury (Hg)
      contamination in the marine environment, although information on flightless
      species like penguins remains limited. In order to assess the use of penguins as
      bioindicators of Hg contamination in subantarctic and Antarctic marine
      ecosystems, Hg concentrations were evaluated in the feathers of the four species
      that breed on the Kerguelen Islands in the southern Indian Ocean. Compared to
      other seabirds, adult Kerguelen penguins had low to moderate feather Hg
      concentrations, with an average ranging from 1.96 +/- 0.41 MUgg(-1) dry weight in
      the southern rockhopper penguin to 5.85 +/- 3.00 MUg g(-1) dry weight in the
      gentoo penguin. The species was a major determinant of Hg contamination, with
      feather Hg concentrations being lower in the oceanic species (king and crested
      penguins) than in the coastal one (gentoo penguin). In all species however,
      feather Hg concentrations were higher in adults than in chicks, reflecting the
      different periods of Hg bioaccumulation in the internal tissues of the two age
      classes. The relationship between adult penguin trophic ecology and Hg burdens
      was investigated using stable isotopes. Feeding habits (reflected by delta(15)N
      values) had a greater effect on adult feather Hg concentrations when compared to
      foraging habitats (reflected by delta(13)C values), indicating Hg
      biomagnification in Kerguelen neritic and oceanic waters. Dietary preferences
      were crucial in explaining individual feather Hg concentrations, as highlighted
      by intra-specific variation in Hg levels of gentoo penguins sampled at two
      different breeding sites of the archipelago. Penguins appear to reflect Hg
      bioavailability reliably in their foraging environment and could serve as
      efficient bioindicators of Hg contamination in the Southern Ocean on different
      spatial and temporal scales.

PMID- 23542488
TI  - Discrete mathematical data analysis approach: a valuable assessment method for
      sustainable chemistry.
AB  - Sustainable/Green Chemistry is a chemical philosophy encouraging the design of
      products and processes that reduce or eliminate the use and generation of
      hazardous substances. In this respect, metrical scientific disciplines like
      Chemometrics are important, because they indicate criteria for chemicals being
      hazardous or not. We demonstrated that sustainable principles in the disciplines
      Green Chemistry, Green Engineering, and Sustainability in Information Technology
      have main aspects in common. The use of non-hazardous chemicals or the more
      efficient use of chemical substances is one of these aspects. We take a closer
      look on the topic of the hazards of chemical substances. Our research focuses on
      data analyses concerning environmental chemicals named Persistent Organic
      Pollutants (POPs), which are found all over the world and pose a large risk to
      environment as well as to humans. The evaluation of the data is a major step in
      the elucidation of the danger of these chemicals. The data analysis method
      demonstrated here, is based on the theory of partially ordered sets and provides
      a generalized ranking. In our approach we investigate data sets of breast milk
      samples of women in Denmark, Finland, and Turkey which contained measurable
      levels of 20 POPs. The goal is twofold: On the one side the hazardous chemicals
      are to be identified and on the other side possible differences among the three
      nations should be detected, because in that case possible different uptake
      mechanisms may be supposed. The data analysis is performed by the free available
      software package PyHasse, written by the third author. We conclude that the data
      analysis method can well be applied for distinguishing between more or less
      dangerous existing chemicals. Furthermore, it should be used in sustainable
      chemistry in the same manner for detecting more and less sustainable chemicals.

PMID- 23542489
TI  - Fluvial geochemistry in Sao Miguel Island (Azores, Portugal): source and fluxes
      of inorganic solutes in an active volcanic environment.
AB  - River water chemistry in two of the major rivers in Sao Miguel Island (Azores
      archipelago, Portugal) has been characterized monthly between June 2010 and
      October 2011 in order to estimate the main geochemical processes that explain
      water composition and to estimate solute fluxes and the thermal water input to
      rivers. Both rivers (Ribeira Grande - RRG, and Ribeira Quente - RRQ) drain active
      trachytic central volcanoes. The number of sampling stations is seven in RRG and
      six in RRQ. Rivers are mainly slightly acid to basic in nature (pH in the range
      5.41-8.70 in RRG and 5.90-8.10 in RRQ) and from the Na-HCO3 and Na-HCO3-Cl water
      types. In both cases water temperature increases towards the river mouth and
      median values are slightly higher in Ribeira Quente (15.5-22.4 degrees C)
      comparing to Ribeira Grande river (15.2-19.7 degrees C). Electrical conductivity
      suggests poorly mineralized waters (139-456 MUS/cm in RRG and 209-402 MUS/cm in
      RRQ, and values increase downstream. Higher solute fluxes are associated to HCO3
      and Na, and the total CO2 flux is equal to 3647 t/yr in RRQ and 7546 t/yr in RRG.
      Mixture with thermal water discharges also influences river water chemistry and
      in RRQ the contribution to the annual average discharge rate was estimated in
      2.96*10(6)m(3)/yr (12.8% of overall discharge rate in the watershed). In RRG
      thermal water discharges were estimated in 2.4*10(6)m(3)/yr (14.9% of the
      discharge rate). The minimum total CO2-consumption associated with low
      temperature weathering is equal to 0.58*10(6)mol/km(2)/yr in Ribeira Quente river
      and equal to 0.78*10(6)mol/km(2)/yr in Ribeira Grande river.

PMID- 23542490
TI  - Differential mercury transfer in the aquatic food web of a double basined lake
      associated with selenium and habitat.
AB  - Food web trophodynamics of total mercury (THg) and selenium (Se) were assessed
      for the double-basined ultraoligotrophic system of Lake Moreno, Patagonia. Each
      basin has differing proportions of littoral and pelagic habitats, thereby
      providing an opportunity to assess the importance of habitat (e.g. food web
      structure or benthic MeHg production) in the transfer of Hg and Se to top trophic
      fish species. Pelagic plankton, analyzed in three size classes (10-53, 53-200,
      and >200 MUm), had very high [THg], exceeding 200 MUg g(-1) dry weight (DW) in
      the smallest, and a low ratio of MeHg to THg (0.1 to 3%). In contrast, [THg] in
      littoral macroinvertebrates showed lower values (0.3 to 1.8 MUg g(-1) DW).
      Juvenile and small fish species feeding upon plankton had higher [THg] (0.2 to 8
      MUg g(-1) muscle DW) compared to large piscivore fish species (0.1 to 1.6 MUg g(
      1) muscle DW). Selenium concentrations exhibited a much narrower variation range
      than THg in the food web, varying from 0.5 to 2.7 MUg g(-1) DW. Molar Se:Hg
      ratios exceeded 1 for the majority of organisms in both basins, with most ratios
      exceeding 10. Using stable nitrogen isotopes as indicator of trophic level, no
      significant correlations were found with [THg], [Se] or Se:Hg. The apparent lack
      of biomagnification trends was attributed to elevated [THg] in plankton in the
      inorganic form mostly, as well as the possibility of consistent Se supply
      reducing the biomagnification in the food web of the organic portion of THg.

PMID- 23542492
TI  - A flexible Bayesian model for describing temporal variability of N2O emissions
      from an Australian pasture.
AB  - Soil-based emissions of nitrous oxide (N2O), a well-known greenhouse gas, have
      been associated with changes in soil water-filled pore space (WFPS) and soil
      temperature in many previous studies. However, it is acknowledged that the
      environment-N2O relationship is complex and still relatively poorly unknown. In
      this article, we employed a Bayesian model selection approach (Reversible jump
      Markov chain Monte Carlo) to develop a data-informed model of the relationship
      between daily N2O emissions and daily WFPS and soil temperature measurements
      between March 2007 and February 2009 from a soil under pasture in Queensland,
      Australia, taking seasonal factors and time-lagged effects into account. The
      model indicates a very strong relationship between a hybrid seasonal structure
      and daily N2O emission, with the latter substantially increased in summer. Given
      the other variables in the model, daily soil WFPS, lagged by a week, had a
      negative influence on daily N2O; there was evidence of a nonlinear positive
      relationship between daily soil WFPS and daily N2O emission; and daily soil
      temperature tended to have a linear positive relationship with daily N2O emission
      when daily soil temperature was above a threshold of approximately 19 degrees C.
      We suggest that this flexible Bayesian modeling approach could facilitate greater
      understanding of the shape of the covariate-N2O flux relation and detection of
      effect thresholds in the natural temporal variation of environmental variables on
      N2O emission.

PMID- 23542491
TI  - Simple to complex modeling of breathing volume using a motion sensor.
AB  - PURPOSE: To compare simple and complex modeling techniques to estimate categories
      of low, medium, and high ventilation (VE) from ActiGraphTM activity counts.
      METHODS: Vertical axis ActiGraphTM GT1M activity counts, oxygen consumption and
      VE were measured during treadmill walking and running, sports, household chores
      and labor-intensive employment activities. Categories of low (<19.3 l/min),
      medium (19.3 to 35.4 l/min) and high (>35.4 l/min) VEs were derived from activity
      intensity classifications (light <2.9 METs, moderate 3.0 to 5.9 METs and vigorous
      >6.0 METs). We examined the accuracy of two simple techniques (multiple
      regression and activity count cut-point analyses) and one complex (random forest
      technique) modeling technique in predicting VE from activity counts. RESULTS:
      Prediction accuracy of the complex random forest technique was marginally better
      than the simple multiple regression method. Both techniques accurately predicted
      VE categories almost 80% of the time. The multiple regression and random forest
      techniques were more accurate (85 to 88%) in predicting medium VE. Both
      techniques predicted the high VE (70 to 73%) with greater accuracy than low VE
      (57 to 60%). ActigraphTM cut-points for light, medium and high VEs were <1381,
      1381 to 3660 and >3660 cpm. CONCLUSIONS: There were minor differences in
      prediction accuracy between the multiple regression and the random forest
      technique. This study provides methods to objectively estimate VE categories
      using activity monitors that can easily be deployed in the field. Objective
      estimates of VE should provide a better understanding of the dose-response
      relationship between internal exposure to pollutants and disease.

PMID- 23542493
TI  - In vitro and in vivo characterization of meloxicam nanoparticles designed for
      nasal administration.
AB  - The nasal pathway represents a non-invasive route for delivery of drugs to the
      systemic circulation. Nanonization of poorly soluble drugs offers a possibility
      to increase dissolution properties, epithelial permeability or even
      bioavailability. The aim of the present study was to use in vitro methods to
      screen formulations which were intended for nasal application, and to perform
      animal experiments for recognizing the differences in plasmakinetics of
      intranasal- and oral-administered meloxicam nanoparticles. Due to nanonization
      the solubility of meloxicam elevated up to 1.2mg/mL, additionally the extent of
      dissolution also increased, complete dissolution was observed in 15 min.
      Favorable in vitro diffusion profile of meloxicam nanoparticles was observed and
      their epithelial permeability through human RPMI2650 cells was elevated. The
      pharmacokinetic parameters were significantly increased when meloxicam was
      administered as nanoparticles to rats either nasally (increase of Cmax 2.7-fold,
      AUC 1.5-fold) or orally (increase of C(max) 2.4-fold, AUC 2-fold) as compared to
      physical mixture of the drug and the excipients.

PMID- 23542494
TI  - Oily nanosuspension for long-acting intramuscular delivery of curcumin
      didecanoate prodrug: preparation, characterization and in vivo evaluation.
AB  - The objective of this study was to prepare the nanocrystals of curcumin
      didecanoate (CurDD) by wet ball milling and to investigate the comparative
      pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.)
      administration to rats. Upon optimizing the wet ball milling parameters, CurDD
      nanocrystals were produced with median particle size of ~500 nm and the freeze
      dried nanocrystals were readily dispersed in peanut oil to form stable
      nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance
      from the injection site after i.m. injection, compared to microsuspension (~5
      MUm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml)
      was observed for the former than that for the latter (18.5 ng/ml). In addition,
      the nanosuspension provided significant higher plasma curcumin concentrations and
      brain CurDD contents for at least 15 days than the microsuspension, except for
      the initial times. A single i.m. injection of nanosuspension appeared to achieve
      reversal effect on reserpine-induced hypothermia for at least 13 days. This study
      demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable
      for sustained delivery of curcumin, potentially applicable to elicit a long
      lasting antidepressant effect.

PMID- 23542496
TI  - A dual colorimetric and fluorescent sensor for lead ion based on naphthalene
      hydrazone derivative.
AB  - A new compound, 2-boronobenzaldehyde-(2'-hydroxyl-4'-sulfonic acid) naphthalene
      hydrazone (1), was synthesized and its structure was characterized by proton
      nuclear magnetic resonance, mass and element analyses. The presence of Pb(2+) led
      1 to undergo colorimetric and fluorescent changes, which were detectable with the
      naked eye. Thus, a dual spectral response for Pb(2+) detection was introduced. In
      KH2PO4-NaOH buffer aqueous solution (pH 6.0), 1 exhibited fluorescence
      enhancement at 568 nm and hyperchromicity at 595 nm upon the addition of Pb(2+).
      The fluorescent intensity change was proportionate to the concentration of Pb(2+)
      with a dynamic working range of 5.0*10(-7) mol L(-1) to 1.0*10(-4) mol L(-1) and
      a detection limit of 3.7*10(-8) mol L(-1). The fluorometric method was
      successfully applied for the detection of Pb(2+) water of Qianhu Lake and soil in
      Nanchang university campus. The recoveries were 111-116% for water and 97.6% for
      soil respectively, determined via the standard addition method.

PMID- 23542495
TI  - Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers:
      photophysical and physicochemical characterisation, release and phototoxicity in
      vitro.
AB  - Nanoparticles of poly(d,l-lactide-co-glycolide), poly(d,l-lactide) and
      polyethylene glycol-block-poly(d,l-lactide) were developed to encapsulate
      chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used
      in photodynamic therapy (PDT). The mean nanoparticle size varied from 115 to 274
      nm, and the encapsulation efficiency ranged from 57% to 96% due to drug
      precipitation induced by different types of polymer. All nanoparticle
      formulations presented negative zeta potential values (-37 mV to -59 mV),
      explaining their colloidal stability. The characteristic photophysical parameters
      were analysed: the absorption spectrum profile, fluorescence quantum yield and
      transient absorbance decay, with similar values for free and nanoparticles of
      AlClPc. The time-resolved spectroscopy measurements for AlClPc triplet excited
      state lifetimes indicate that encapsulation in nanocapsules increases triplet
      lifetime, which is advantageous for PDT efficiency. A sustained release profile
      over 168 h was obtained using external sink method. An in vitro phototoxic effect
      higher than 80% was observed in human fibroblasts at low laser light doses (3
      J/cm(2)) with 10 MUM of AlClPc. The AlClPc loaded within polymeric nanocapsules
      presented suitable physical stability, improved photophysical properties,
      sustained released profile and suitable activity in vitro to be considered a
      promising formulation for PDT.

PMID- 23542497
TI  - Pressure-broadening of water transitions near 7180 cm(-1) by helium isotopes.
AB  - In this study, pressure-broadening parameters for several H2O transitions near
      7180 cm(-1) are obtained which describe collisions with (3)He and (4)He. The
      sensitivity of those parameters to choice of theoretical line profile (Galatry
      vs. Voigt) is investigated. H2O is an important species in atmospheric chemistry
      and astronomy. Because of this, basic fundamental research, which explores the
      nature of the H2O spectrum in the presence of different gases of varying physical
      properties, can provide useful reference data which can be applied in the fields
      of atmospheric and planetary remote sensing. Measurements were made using an
      intensity-modulated laser photoacoustic spectrometer. Results from the present
      work show that Galatry line profiles, with a constrained narrowing parameter,
      more accurately describe experimental spectra than Voigt profiles over a wide
      range of experimental pressure conditions. Average pressure-broadening parameters
      were found to be 0.0216 cm(-1)/atm and 0.0209 cm(-1)/atm for H2O in (3)He and
      (4)He, respectively, and were compared to a literature model for the mass
      dependence of line broadening. Specific values were obtained for each transition
      with nominal combined uncertainties of 2-6%.

PMID- 23542498
TI  - Structural brain correlates of executive engagement in working memory: children's
      inter-individual differences are reflected in the anterior insular cortex.
AB  - Although the development of executive functions has been extensively investigated
      at a neurofunctional level, studies of the structural relationships between
      executive functions and brain anatomy are still scarce. Based on our previous
      meta-analysis of functional neuroimaging studies examining executive functions in
      children (Houde, Rossi, Lubin, and Joliot, (2010). Developmental Science, 13, 876
      885), we investigated six a priori regions of interest: the left anterior insular
      cortex (AIC), the left and the right supplementary motor areas, the right middle
      and superior frontal gyri, and the left precentral gyrus. Structural magnetic
      resonance imaging scans were acquired from 22 to 10-year-old children. Local gray
      matter volumes, assessed automatically using a standard voxel-based morphometry
      approach, were correlated with executive and storage working memory capacities
      evaluated using backward and forward digit span tasks, respectively. We found an
      association between smaller gray matter volume--i.e., an index of neural
      maturation--in the left AIC and high backward memory span while gray matter
      volumes in the a priori selected regions of interest were not linked with forward
      memory span. These results were corroborated by a whole-brain a priori free
      analysis that revealed a significant negative correlation in the frontal and
      prefrontal regions, including the left AIC, with the backward memory span, and in
      the right inferior parietal lobe, with the forward memory span. Taken together,
      these results suggest a distinct and specific association between regional gray
      matter volume and the executive component vs. the storage component of working
      memory. Moreover, they support a key role for the AIC in the executive network of
      children.

PMID- 23542499
TI  - Altered brain structure in Chinese dyslexic children.
AB  - Due to the logographic nature of the writing system, learning to read Chinese
      places heavy demands on encoding of orthographic forms through rote memorization.
      Moreover, phonology has to often be retrieved from memory during reading because
      of the inconsistent mapping between characters and their pronunciations. Using
      optimized voxel-based morphometry, we examined differences in volumetrics between
      children with reading disability (RD, 10-12 years old) and age-matched typically
      developing (TD) children. Our study shows reduced gray matter volume (GMV) for RD
      in right inferior occipital gyrus and left inferior frontal gyrus, consistent
      with previous studies suggesting that Chinese dyslexics have deficits in
      orthographic and phonological processing. The deficit in phonological processing
      was further supported by reductions in white matter volumes (WMV) in left
      precentral gyrus. Greater deficits in ortho-phonological processing may be
      associated with semantic compensation, as lower skill RD children showed greater
      GMV in anterior temporal cortex, even though as a group they showed less GMV in
      this region compared to TD. Perhaps most interestingly, we showed reduced GMV in
      bilateral ventromedial prefrontal cortices (vmPFC) and this was correlated with
      reductions in WMV within vmPFC, suggesting that RD have deficits in memory
      retrieval. Moreover, these GMV alterations in vmPFC for the RD were correlated
      with alterations in right parahippocampal gyrus, which also showed a reduced GMV,
      suggesting that RD have a correlated deficit in memory encoding. Our results are
      consistent with previous studies suggesting that Chinese dyslexics have deficits
      in visuo-orthographic and phonological processing, but our study importantly
      suggests deficits in memory encoding and retrieval, perhaps due to the unique
      demands of the Chinese writing system.

PMID- 23542500
TI  - Laterality effects in normal subjects' recognition of familiar faces, voices and
      names. Perceptual and representational components.
AB  - A growing body of evidence suggests that a different hemispheric specialization
      may exist for different modalities of person identification, with a prevalent
      right lateralization of the sensory-motor systems allowing face and voice
      recognition and a prevalent left lateralization of the name recognition system.
      Data supporting this claim concern, however, much more disorders of familiar
      people recognition observed in patients with focal brain lesions than results of
      experimental studies conducted in normal subjects. These last data are sparse and
      in part controversial, but are important from the theoretical point of view,
      because it is not clear if hemispheric asymmetries in the recognition of faces,
      voices and names are limited to their perceptual processing, or also extend to
      the domain of their cortical representations. The present review has tried to
      clarify this issues, taking into account investigations that have evaluated in
      normal subjects laterality effects in recognition of familiar names, faces and
      voices, by means of behavioural, neurophysiological and neuroimaging techniques.
      Results of this survey indicate that: (a) recognition of familiar faces and
      voices show a prevalent right lateralization, whereas recognition of familiar
      names is lateralized to the left hemisphere; (b) the right hemisphere prevalence
      is greater in tasks involving familiar than unfamiliar faces and voices, and the
      left hemisphere superiority is greater in the recognition of familiar than
      unfamiliar names. Taken together, these data suggest that hemispheric asymmetries
      in the recognition of faces, voices and names are not limited to their perceptual
      processing, but also extend to the domain of their cortical representations.

PMID- 23542501
TI  - Urinary retention for the neurologist.
AB  - Urinary retention is a common problem, most often due to an anatomical lesion in
      the urinary tract causing obstruction, such as a urethral stricture or prostate
      enlargement. However, a subset of patients have no structural urological lesion,
      and so require neurological evaluation. We present a patient with acute urinary
      retention who was found to have chronic meningitis, and review the neurological
      causes for urinary retention. 

PMID- 23542502
TI  - Ileosigmoid knot.
AB  - Ileosigmoid knotting, also known as compound volvulus or double Volvulus, is a
      rare cause of acute intestinal obstruction. In this condition the ileum wraps
      around the base of the sigmoid colon and forms a knot. The condition is serious,
      generally progressing rapidly to gangrene of both ileum and sigmoid colon.
      Ileosigmoid knotting is an unusual entity in the West, but is comparatively
      common in certain African, Asian and Middle Eastern nations. Awareness of the
      condition is essential for prompt diagnosis and optimal management. This article
      will focus on the etiopathogenesis, presentation, diagnostic modalities, surgical
      interventions and outcome with review of articles and case reports published till
      date.

PMID- 23542503
TI  - Amplification of antioxidant activity of haptoglobin(2-2)-hemoglobin at
      pathologic temperature and presence of antibiotics.
AB  - It is clear that Haptoglobin binds to Hemoglobin strongly and irreversibly. This
      binding, protects body tissues against heme-mediated oxidative tissue damages via
      peroxidase activity of Haptoglobin-Hemoglobin complex. Peroxidase activity of
      Haptoglobin(2-2)-Hemoglobin complex was determined via measurement of following
      increase in absorption of produced tetraguaiacol as the second substrate of
      Haptoglobin-Hemoglobin complex by UV-Vis spectrophotometer at 470 nm and 42
      degrees C. The results are showing that peroxidase activity of Haptoglobin(2-2)
      Hemoglobin complex is modulated by homotropic effect of hydrogen peroxide as the
      allosteric substrate. On the other hand, antioxidant activity of Haptoglobin(2-2)
      Hemoglobin is increased via heterotropic effect of two antibiotics (especially
      ampicillin) on the peroxidase activity of the complex. The condition of
      pathologic temperature along with the administration of ampicillin and/or
      coamoxiclav is in favor of amplification in antioxidant activity of Haptoglobin(2
      2)-Hemoglobin and combating against free radicals in individuals with Hp2-2
      phenotype. Therefore, oxidative stress effects have been diminished in the
      population with this phenotype.

PMID- 23542504
TI  - Prognosis of vasculitis associated myelodysplasia.
AB  - Systemic and immune manifestations have been reported in patients with MDS. The
      correlation between immunological abnormalities and prognosis in myelodysplastic
      syndrome patients remains controversial. Most of the authors agree that the
      median survival in myelodysplastic syndrome is not related to the presence of
      systemic and immune manifestations, but only with the existence of a systemic
      vasculitis. 

PMID- 23542505
TI  - Is it time for biosimilars in autoimmune diseases?
AB  - The last two decades have witnessed a revolution in the treatment of autoimmune
      diseases due to the introduction of biological agents which, although now
      included as standard treatment in patients with autoimmune rheumatological,
      dermatological and gastrointestinal diseases. The use of biological agents is
      associated with greater costs compared with the mainly anti-inflammatory and
      immunosuppressant drugs used in the pre-biological era. Biosimilars are highly
      similar copies of biological drugs, but not identical to approved 'reference'
      agents. Biological agents are complex proteins involved in the immune response
      and their exact replicas are extremely difficult, if not impossible, to obtain.
      Three scenarios have converged to provide a specific opportunity for biosimilars
      in autoimmune diseases: growing demand for biologics due to successful clinical
      use; the nearing of patent expiry for the four top-selling biological brands; and
      the search to reduce health costs due to the financial crisis. We aimed to review
      the crucial topics of efficacy, safety and regulatory approach of upcoming
      biosimilars. 

PMID- 23542506
TI  - Biologic therapies and systemic bone loss in rheumatoid arthritis.
AB  - Chronic inflammation affects bone metabolism leading to disequilibrium in the
      rates of bone resorption and repair and subsequently to local and generalized
      bone loss. Osteoporosis represents an important co-morbidity of rheumatoid
      arthritis (RA) patients, which exhibit increased fracture risk. Osteoclasts play
      a pivotal role in the development and progression of bone loss, while resident
      synovial cells such as T cells, monocytes and synovial fibroblasts have been
      identified as sources of osteoclast differentiation signals in RA. This process
      is mainly mediated through the receptor activator of nuclear-kappa B ligand
      (RANKL) signalling system, which is upregulated by numerous proinflammatory
      cytokines involved in the pathogenesis of RA. Improved knowledge of the
      association between cells and cytokines of the immune system and their
      relationship to bone remodeling has revealed several promising targets for the
      treatment of inflammatory bone loss in RA. In this respect, initiation of
      biologic therapies targeting inflammatory cytokines and/or lymphocyte activation
      has modified RA therapy not only by blocking local and systemic inflammatory
      cascades but also by providing beneficial effects against bone and joint
      degradation. In this article we briefly present the modern view of the mechanisms
      that govern inflammatory bone loss, highlighting the role of cytokine-induced
      molecular pathways, and discuss in detail the effects of different biologic
      treatment strategies on bone mass in RA patients. 

PMID- 23542507
TI  - Vitamin D effects on musculoskeletal health, immunity, autoimmunity,
      cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a
      review of recent evidence.
AB  - BACKGROUND: Optimal vitamin D intake and its status are important not only for
      bone and calcium-phosphate metabolism, but also for overall health and well
      being. Vitamin D deficiency and insufficiency as a global health problem are
      likely to be a risk for wide spectrum of acute and chronic illnesses. METHODS: A
      review of randomized controlled trials, meta-analyses, and other evidence of
      vitamin D action on various health outcomes. RESULTS: Adequate vitamin D status
      seems to be protective against musculoskeletal disorders (muscle weakness, falls,
      fractures), infectious diseases, autoimmune diseases, cardiovascular disease,
      type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive
      dysfunction and mental illness, and other diseases, as well as infertility and
      adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is
      associated with all-cause mortality. CONCLUSIONS: Adequate vitamin D
      supplementation and sensible sunlight exposure to reach optimal vitamin D status
      are among the front line factors of prophylaxis for the spectrum of disorders.
      Supplementation guidance and population strategies for the eradication of vitamin
      D deficiency must be included in the priorities of physicians, medical
      professionals and healthcare policy-makers.

PMID- 23542508
TI  - A study on the nucleolar organizer regions-as a tumour proliferative marker in
      cervical smears.
AB  - AIM: To study the Argyrophilic Nucleolar Organizer Regions (AgNOR) as a cell
      proliferative marker in cervical smears and to assess its counts with the
      severity of the lesions on Papanicolaou (PAP) stained cervical smears. MATERIAL
      AND METHOD: The present study was a prospective experimental study which was
      carried out at Jawaharlal Nehru Medical College in a span of 2 years. 50 high
      risk cases were selected from the Gynaecological OPD. The cervical smears were
      collected in pairs, one for the conventional PAP staining and the other one for
      the specialized AgNOR staining. STATISTICAL ANALYSIS: The Student's unpaired 't'
      test was used. OBSERVATION: There was a progressive rise in the AgNOR counts with
      the severity of the lesions [normal cervix< chronic cervicitis< low squamous
      intraepithelial lesion (LSIL)< High Squamouus Intraepithelial Lesion (HSIL)
      carcinoma cervix i.e. 1.75 < 2.09 < 2.81 < 4.17< 5.98 respectively]. Each lesion
      had a significant AgNOR value which helped in differentiating it from its
      precursor lesion. CONCLUSION: The AgNOR counts have been immensely helpful as
      they behave as a cell proliferative marker, aiding the diagnosis which is made
      through the cervical PAP stained smears and letting the cytopathologist
      understand the exact stage of the cervical lesion.

PMID- 23542509
TI  - Histopathology of the liver of Mastacembelus armatus (Lecepede, 1800) due to
      trematode parasite, Allocreadium khami n.sp.
AB  - The trematode parasite, Allocreadium khami n.sp. cyst is found infected to the
      liver of freshwater fish, Mastacembelus armatus (Lecepede, 1800).
      Histopathological studies have been made to access the extent of damage caused by
      the parasite. The changes that have witnessed in the liver includes inflammation
      of liver, change of colour and formation of cysts. The histopathological changes
      include disarray in the arrangement of hepatochords, arrangement and rupture of
      hepatocytes.

PMID- 23542510
TI  - Silencing of the Charcot-Marie-Tooth disease-associated gene GDAP1 induces
      abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing
      store-operated Ca2+ entry.
AB  - GDAP1 is an outer mitochondrial membrane protein that acts as a regulator of
      mitochondrial dynamics. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth
      (CMT) neuropathy. We show that GDAP1 interacts with the vesicle-organelle
      trafficking proteins RAB6B and caytaxin, which suggests that GDAP1 may
      participate in the mitochondrial movement within the cell. GDAP1 silencing in the
      SH-SY5Y cell line induces abnormal distribution of the mitochondrial network,
      reduces the contact between mitochondria and endoplasmic reticulum (ER) and
      alters the mobilization of mitochondria towards plasma membrane upon depletion of
      ER-Ca(2+) stores. GDAP1 silencing does not affect mitochondrial Ca(2+) uptake, ER
      Ca(2+), or Ca(2+) flow from ER to mitochondria, but reduces Ca(2+) inflow through
      store-operated Ca(2+) entry (SOCE) following mobilization of ER-Ca(2+) and SOCE
      driven Ca(2+) entry in mitochondria. Our studies suggest that the pathophysiology
      of GDAP1-related CMT neuropathies may be associated with abnormal distribution
      and movement of mitochondria throughout cytoskeleton towards the ER and
      subplasmalemmal microdomains, resulting in a decrease in SOCE activity and
      impaired SOCE-driven Ca(2+) uptake in mitochondria.

PMID- 23542512
TI  - Amelioration of cyclophosphamide-induced hepatotoxicity by the root extract of
      Decalepis hamiltonii in mice.
AB  - Hepatoprotective potential of the aqueous extract of the roots of Decalepis
      hamiltonii (DHA) against cyclophosphamide (CP)-induced oxidative stress has been
      investigated in mice. Administration of CP (25mg/kg b.w., i.p) for 10 days
      induced hepatic damage as indicated by the serum marker enzymes aspartate and
      alanine transaminases (AST, ALT), alkaline phosphatase (ALP) and lactate
      dehydrogenase (LDH). Parallel to these changes CP induced oxidative stress in the
      liver as evident from the increased lipid peroxidation (LPO), reactive oxygen
      species (ROS), depletion of glutathione (GSH), and reduced activities of the
      antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S
      transferase (GST). Treatment with DHA (50 and 100 mg/kg b.w., po) mitigated the
      CP-induced oxidative stress. Moreover, expression of genes for the antioxidant
      enzymes, were down-regulated by CP treatment which was reversed by DHA. Our study
      shows the DHA protected the liver from toxicity induced by CP and therefore, it
      could be serve as a safe medicinal supplement during cyclophosphamide
      chemotherapy.

PMID- 23542511
TI  - Calpains mediate axonal cytoskeleton disintegration during Wallerian
      degeneration.
AB  - In both the central nervous system (CNS) and peripheral nervous system (PNS),
      transected axons undergo Wallerian degeneration. Even though Augustus Waller
      first described this process after transection of axons in 1850, the molecular
      mechanisms may be shared, at least in part, by many human diseases. Early
      pathology includes failure of synaptic transmission, target denervation, and
      granular disintegration of the axonal cytoskeleton (GDC). The Ca(2+)-dependent
      protease calpains have been implicated in GDC but causality has not been
      established. To test the hypothesis that calpains play a causal role in axonal
      and synaptic degeneration in vivo, we studied transgenic mice that express human
      calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve
      axons. Five days after optic nerve transection and 48 h after sciatic nerve
      transection, robust neurofilament proteolysis observed in wild-type controls was
      reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in
      sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In
      addition, hCAST expression preserved the morphological integrity of neuromuscular
      junctions. However, compound muscle action potential amplitudes after nerve
      transection were similar in wild-type and hCAST mice. These results, in total,
      provide direct evidence that calpains are responsible for the morphological
      degeneration of the axon and synapse during Wallerian degeneration.

PMID- 23542513
TI  - 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone inhibits nitric oxide production in
      lipopolysaccharide-stimulated BV2 microglia via NF-kappaB suppression and Nrf-2
      dependent heme oxygenase-1 induction.
AB  - In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (5HHMF)
      from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated
      NO production by suppressing the expression of inducible NO synthase (iNOS) in
      BV2 microglia. In addition, 5HHMF blocked LPS-induced phosphorylation of IkappaB,
      resulting in suppression of the nuclear translocation of nuclear factor-kappaB
      (NF-kappaB) subunits, namely p65 and p50, which are important molecules involved
      in the regulation of iNOS expression. Pyrrolidine dithiocarbamate (PDTC), a
      specific NF-kappaB inhibitor, along with 20S proteasome inhibitor (PSI)
      significantly inhibited LPS-induced iNOS expression, which indirectly suggested
      that 5HHMF downregulated iNOS expression by suppressing NF-kappaB activity. Thus,
      we found that 5HHMF enhances heme oxygenase-1 (HO-1) expression via nuclear
      factor-erythroid 2-related factor 2 (Nrf2) activation. In addition, cobalt
      protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS
      induced NO production. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1
      inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO
      production. Further, 5HHMF increased specific DNA-binding activity of Nrf2, and
      transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO
      inhibition, which was followed by suppression of HO-1 activity. Taken together,
      our findings indicate that 5HHMF suppresses NO production through modulation of
      iNOS, consequently suppressing NF-kappaB activity and induction of Nrf2-dependent
      HO-1 activity.

PMID- 23542514
TI  - Solvent dependent frequency shift and Raman noncoincidence effect of S=O
      stretching mode of Dimethyl sulfoxide in liquid binary mixtures.
AB  - The isotropic and anisotropic Raman peak frequencies of S=O stretching mode of
      Dimethyl sulfoxide (DMSO) have been discussed in different chemical and isotopic
      solvent molecules using different mechanisms. The shifting of peak frequency in
      further dilution of DMSO with solvent molecule is observed for all solvents.
      Transition dipole - transition dipole interaction and hydrogen bonding may play a
      major role in shifting of peak frequencies. The non-coincidence effect (NCE) of
      DMSO was determined for all the solvents and compared with four theoretical
      models such as McHale's model, Mirone's modification of McHale's model, Logan's
      model and Onsager-Frohlich dielectric continuum model respectively. Most of the
      theoretical models are largely consistent with our experimental data.

PMID- 23542515
TI  - UV irradiation study of a tripeptide isolated in an argon matrix: a tautomerism
      process evidenced by infrared and X-ray photoemission spectroscopies.
AB  - Matrix isolation is a powerful tool for studying photochemical processes
      occurring in isolated molecules. In this way, we characterized the chemical
      modifications occurring within a tri peptide molecule, IGF, when exposed to the
      influence of Ultraviolet (UV) irradiation. This paper first describes the
      successful formation of the tripeptide (IGF) argon matrix under vacuum
      conditions, followed by the in situ UV irradiation and characterization of the
      molecular matrix reactivity after UV-irradiation. These studies have been
      performed by combining two complementary spectroscopic techniques, Fourier
      Transform Reflexion Absorption Spectroscopy (FT-IRRAS) and X-ray Photoelectron
      Spectroscopy (XPS). The IR spectra of the isolated peptide-matrix, before and
      after UV irradiation, revealed significant differences that could be associated
      either to a partial deprotonation of the molecule or to a tautomeric conversion
      of some amide bonds to imide ones on some peptide molecules. XPS analyses
      undoubtedly confirmed the second hypothesis; the combination of IRRAS and XPS
      results provide evidence that UV irradiation of peptides induces a chemical
      reaction, namely a shift of the double bond, meaning partial conversion from
      amide tautomer into an imidic acid tautomer.

PMID- 23542516
TI  - Nonlinear optical analyses of organic N-(9-Anthrylmethylidene) methylamine Schiff
      base.
AB  - The organic NLO Schiff base of N-(9-Anthrylmethylidene) methylamine was
      synthesized by condensation process. The material was characterized through
      Powder XRD, FT-IR, and Raman techniques. The various planes of reflection are
      identified from the Powder XRD pattern. The formation of Schiff base is confirmed
      through FT-IR and Raman analysis. The intra molecular charge transfer interaction
      and the existence of the first-order molecular hyperpolarizability (beta) are
      identified from the red shift of the UV-Vis analysis. The structure of the
      molecule was optimized by density functional theory (DFT) using B3LYP method with
      6-31G basis set. The NBO analysis is used to interpret the delocalization. The
      dipole moment and first hyperpolarizability values were also computed by HF/6
      31G. These values indicate that the compound is a good candidate with nonlinear
      optical properties. This is the first time report on the existence of a second
      harmonic generation (SHG), chi(2), efficiency that has been identified by Powder
      Kurtz-Perry method.

PMID- 23542517
TI  - Preparation, spectroscopic and thermal characterization of new charge-transfer
      complexes of ethidium bromide with pi-acceptors. In vitro biological activity
      studies.
AB  - Ethidium bromide (EtBr) is a strong DNA binder and has been widely used to probe
      DNA structure in drug-DNA and protein-DNA interaction. Four new charge-transfer
      (CT) complexes consisting of EtBr as donor and quinol (QL), picric acid (PA),
      tetracyanoquinodimethane (TCNQ) or dichlorodicyanobenzoquinone (DDQ) as
      acceptors, were synthesized and characterized by elemental analysis, electronic
      absorption, spectrophotometric titration, IR, Raman, (1)H NMR and X-ray powder
      diffraction (XRD) techniques. The stoichiometry of these complexes was found to
      be 1:2 ratio and having the formula [(EtBr)(acceptor)]. The thermal stability of
      the synthesized CT complexes was investigated using thermogravimetric (TG)
      analyses, and the morphology and particle size of these complexes were obtained
      from scanning electron microscopy (SEM). The CT complexes were also tested for
      its antibacterial activity against two Gram-positive bacteria Staphylococcus
      aureus and Bacillus subtilis and two Gram-negative bacteria; Escherichia coli and
      Pseudomonas aeuroginosa strains by using Tetracycline as standard and antifungal
      property against Aspergillus flavus and Candida albicans by using amphotericin B
      as standard. The results were compared with the standard drugs and significant
      conclusions were obtained. The results indicated that the [(EtBr)(QL)2] complex
      had exerted excellent inhibitory activity against the growth of the tested
      bacterial strains.

PMID- 23542518
TI  - Synthesis, spectroscopic (FT-IR, FT-Raman, 13C, 1H, UV) study, first order
      hyperpolarizability, NBO analysis, HOMO and LUMO analysis of 2(2-Hydroxyphenyl)-N
      (4-Methylphenyl) Nitrone.
AB  - The title compound, 2(2-Hydroxyphenyl)-N-(4-Methylphenyl) Nitrone (2HPN4MPN) was
      synthesized and characterized by FT-IR, FT-Raman, UV-Vis and (1)HNMR, (13)CNMR
      spectral analysis. The molecular geometry, harmonic vibrational frequencies and
      bonding features of the title compound in the ground state are computed at three
      parameter hybrid functional Lee-Yang-Parr/6-311++G(d,p) levels of theory. The
      most stable conformer of 2HPN4MPN is identified from the computational results.
      The assignments of the vibrational spectra have been carried out with the help of
      normal co-ordinate analysis (NCA) following the scaled quantum mechanical force
      field methodology (SQMF). The UV-Vis spectrum was recorded in chloroform
      solution. The energy and oscillator strength calculated by time-dependent density
      functional theory (TD-DFT) complements the experimental findings. The calculated
      HOMO and LUMO energies confirm that charge transfer occurs within the molecule.
      In addition, DFT calculations of the compound, Molecular Electrostatic Potential
      (MEP), Natural Bond Orbital analysis (NBO) and non-linear optical (NLO)
      properties are performed at B3LYP/6-311++G(d,p) level of theory. Finally, the
      calculations are applied to simulated FT-IR and FT-Raman spectra of the title
      compound which show good agreement with observed spectra.

PMID- 23542519
TI  - Primidone--an antiepileptic drug--characterisation by quantum chemical and
      spectroscopic (FTIR, FT-Raman, 1H, 13C NMR and UV-Visible) investigations.
AB  - The solid phase FTIR and FT-Raman spectra of primidone were recorded in the
      regions 4000-400 cm(-1) and 4000-100 cm(-1), respectively. The vibrational
      spectra were analysed and the observed fundamentals were assigned and analysed.
      The experimental wavenumbers were compared with the theoretical scaled
      vibrational wavenumbers determined by DFT methods. The Raman intensities were
      also determined with B3LYP/6-31G(d,p) method. The total electron density and
      molecular electrostatic potential surface of the molecule were constructed by
      using B3LYP/6-311++G(d,p) method to display electrostatic potential
      (electron+nuclei) distribution. The HOMO and LUMO energies were measured. Natural
      bond orbital analysis of primidone has been performed to indicate the presence of
      intramolecular charge transfer. The (1)H and (13)C NMR spectra were recorded and
      the chemical shifts of the molecule were calculated.

PMID- 23542520
TI  - Distinct ALK-rearranged and VCL-negative papillary renal cell carcinoma variant
      in two adults without sickle cell trait.

PMID- 23542521
TI  - Reply to 'Distinct ALK-rearranged and VCL-negative papillary renal cell carcinoma
      variants in two adults without sickle cell trait'.

PMID- 23542522
TI  - HER-2 intratumoral heterogeneity.

PMID- 23542523
TI  - Letter to the editor regarding 'Seol H, Lee HJ, Choi Y, et al. Intratumoural
      heterogeneity of HER2 gene amplification in breast cancer: its
      clinicopathological significance'.

PMID- 23542524
TI  - Reply to 'Intratumoral heterogeneity of HER2 gene amplification in breast cancer:
      its clinicopathological significance'.

PMID- 23542525
TI  - DDIT3, STT3A (ITM1), ARG2 and FAM129A (Niban, C1orf24) in diagnosing thyroid
      carcinoma: variables that may affect the performance of this antibody-based test
      and promise.

PMID- 23542526
TI  - Reply to 'The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful
      in diagnosing thyroid follicular tumors'.

PMID- 23542527
TI  - Nested melanoma.

PMID- 23542528
TI  - MicroRNAs as prognostic markers in indolent primary cutaneous B-cell lymphoma.

PMID- 23542529
TI  - Evaluation of source water protection strategies: a fuzzy-based model.
AB  - Source water protection (SWP) is an important step in the implementation of a
      multi-barrier approach that ensures the delivery of safe drinking water.
      Available decision-making models for SWP primarily use complex mathematical
      formulations that require large data sets to perform analysis, which limit their
      use. Moreover, most of them cannot handle interconnection and redundancy among
      the parameters, or missing information. A fuzzy-based model is proposed in this
      study to overcome the above limitations. This model can estimate a reduction in
      the pollutant loads based on selected SWP strategies (e.g., storm water
      management ponds, vegetated filter strips). The proposed model employs an export
      coefficient approach and account for the number of animals to estimate the
      pollutant loads generated by different land usages (e.g., agriculture, forests,
      highways, livestock, and pasture land). Water quality index is used for the
      assessment of water quality once these pollutant loads are discharged into the
      receiving waters. To demonstrate the application of the proposed model, a case
      study of Page Creek was performed in the Clayburn watershed (British Columbia,
      Canada). The results show that increasing urban development and poorly managed
      agricultural areas have the most adverse effects on source water quality. The
      proposed model can help decision makers to make informed decisions related to the
      land use and resource allocation.

PMID- 23542530
TI  - Valorization of an agro-industrial waste, mango seed, by the extraction and
      characterization of its cellulose nanocrystals.
AB  - Mango seeds are lignocellulosic agro-industrial residues available in large
      quantities in tropical countries and are simply discarded or used as animal feed.
      They are a natural and renewable resource, and were used to generate new
      polymeric materials in this work. This new materials can be used as alternatives
      to fossil resources such as petroleum. This work aimed to extract and
      characterize cellulose nanocrystals (CN) from mango seed by acid hydrolysis to
      obtain a material suitable as a reinforcing agent in the manufacturing of
      nanocomposites. The fibers of mango seeds were ground in mills and purified
      mainly to remove lignin. The raw mango seed (MS) and the purified mango seed
      (PMS) were analyzed for chemical composition and characterized by infrared and X
      rays. Cellulose nanocrystals from the mango seed (CNM) were isolated by acid
      hydrolysis at 40  degrees C for 10 min, with 20 ml of H2SO4 (11.21 M) used for
      every gram of cellulose. The yield at this step was 22.8%. CNM were needle
      shaped, with high crystallinity (90.6%), good thermal stability (around 248 
      degrees C), a medium length (L) of 123.4 +/- 22.1 nm and a diameter (D) of 4.59
      +/- 2.22 nm, giving an aspect ratio (L/D) of about 34.1 +/- 18.6. The diameter
      measurements of CNM were also confirmed by Scherrer's equation. This work also
      aimed to reuse mango seed produced as industrial waste, giving it a useful
      application and preventing its role as an environmental pollutant.

PMID- 23542531
TI  - Engineering skeletal muscle tissues from murine myoblast progenitor cells and
      application of electrical stimulation.
AB  - Engineered muscle tissues can be used for several different purposes, which
      include the production of tissues for use as a disease model in vitro, e.g. to
      study pressure ulcers, for regenerative medicine and as a meat alternative (1).
      The first reported 3D muscle constructs have been made many years ago and
      pioneers in the field are Vandenburgh and colleagues (2,3). Advances made in
      muscle tissue engineering are not only the result from the vast gain in knowledge
      of biochemical factors, stem cells and progenitor cells, but are in particular
      based on insights gained by researchers that physical factors play essential
      roles in the control of cell behavior and tissue development. State-of-the-art
      engineered muscle constructs currently consist of cell-populated hydrogel
      constructs. In our lab these generally consist of murine myoblast progenitor
      cells, isolated from murine hind limb muscles or a murine myoblast cell line
      C2C12, mixed with a mixture of collagen/Matrigel and plated between two anchoring
      points, mimicking the muscle ligaments. Other cells may be considered as well,
      e.g. alternative cell lines such as L6 rat myoblasts (4), neonatal muscle derived
      progenitor cells (5), cells derived from adult muscle tissues from other species
      such as human (6) or even induced pluripotent stem cells (iPS cells) (7). Cell
      contractility causes alignment of the cells along the long axis of the construct
      (8,9) and differentiation of the muscle progenitor cells after approximately one
      week of culture. Moreover, the application of electrical stimulation can enhance
      the process of differentiation to some extent (8). Because of its limited size (8
      x 2 x 0.5 mm) the complete tissue can be analyzed using confocal microscopy to
      monitor e.g. viability, differentiation and cell alignment. Depending on the
      specific application the requirements for the engineered muscle tissue will vary;
      e.g. use for regenerative medicine requires the up scaling of tissue size and
      vascularization, while to serve as a meat alternative translation to other
      species is necessary.

PMID- 23542532
TI  - The effect of a caffeinated energy drink on various psychological measures during
      submaximal cycling.
AB  - Caffeine containing energy drinks is commonly consumed in the belief that it will
      enhance the quality of an exercise session and enhance mood. However, studies
      examining their efficacy are sparse. The aim of this study was to examine the
      effect of a caffeinated energy drink on leg pain perception, perceived exertion,
      mood state and readiness to invest effort pre, during and post 60 min cycling
      exercise. Fourteen active individuals (7 males, 7 females, mean age +/- S.D.=23.5
      +/- 3.5 years), completed two 60 min cycling trials at an intensity of 60% VO2
      max preceded by ingestion of solutions containing either a caffeinated energy
      drink or placebo using a double-blind, deceptive, crossover design. During
      exercise, RPE (6-20 scale), leg pain (0-10 scale), heart rate (HR) and blood
      lactate (Bla) were recorded. Participants also completed measures of mood state
      and readiness to invest physical effort (RTIPE) pre- and post-exercise. Repeated
      measures analysis of variance was used to assess differences in all variables and
      across time and treatments, with gender used as a between subjects variable.
      Results indicate that HR was significantly higher (P=.002) from 30 to 60 min and
      RPE (P=.0001) and pain perception (P=.0001) were significantly lower from 20 to
      60 min in the energy drink condition compared to placebo. Bla was significantly
      higher (P=.021) in the last 15 min of the energy drink trial and RTIPE (P=.001)
      increased significantly more from pre-ingestion to pre-exercise post-ingestion in
      the energy drink condition compared to placebo. No gender differences were
      evident (P>.05). The data revealed positive effects of energy drink ingestion on
      perception of exertion, leg muscle pain perception and readiness to invest effort
      during submaximal cycling in active adults.

PMID- 23542533
TI  - Endoscopic features associated with ileal pouch failure.
AB  - BACKGROUND: Endoscopic features as predictors in pouch failure have not been
      studied. A well-constructed J-pouch typically has an "owl's eye" appearance in
      the proximal pouch body. We hypothesized that loss of the owl's eyes is
      associated with a high risk for pouch failure. The aim of this study was to
      evaluate the association between the distorted endoscopic appearance of owl's
      eyes and pouch failure. METHODS: A total of 711 available pouch endoscopic images
      from 426 J-pouch patients were reviewed and scored blindly. A scoring system was
      generated for distorted owl's eyes. Multivariable analyses were performed to
      assess the link between the endoscopic feature or other variables and pouch
      failure. RESULTS: A total of 37 patients (8.7%) developed pouch failure, with a
      median of 5.0 (interquartile range, 2.0-11.0) years of follow-up. Multivariable
      analyses showed that 2 or more "beak" abnormalities were associated with failure
      rates of 33.3%, 44.4%, and 72.2% by 5, 10, and 15 years of ileal pouch-anal
      anastomosis, respectively (hazard ratio = 3.7; 95% confidence interval, 1.5-9.0).
      In addition, diagnosis of Crohn's disease or surgical complications, the
      postoperative use of anti-tumor necrosis factor biologics, and a high cuff
      endoscopy inflammation score had statistically significant hazard ratios of 3.2,
      5.8, and 1.5 for pouch failure, respectively. CONCLUSIONS: Distorted appearance
      of "beak" portion of owl's eyes along with Crohn's disease of the pouch or
      surgery-related complications, postoperative use of biologics, and persistent
      cuffitis were the risk factors associated with pouch failure. The assessment of
      endoscopic owl's eye structure may provide an additional clue to predict pouch
      outcome.

PMID- 23542534
TI  - Methotrexate in ulcerative colitis: a nationwide retrospective cohort from the
      Veterans Affairs Health Care System.
AB  - BACKGROUND: There are paucity of data regarding the utility of methotrexate (MTX)
      in the management of ulcerative colitis (UC). The aim of this study was to
      describe the efficacy of MTX in achieving steroid-free remission. METHODS: A
      retrospective cohort study was conducted using the nationwide Veterans Affairs
      database to identify steroid-dependent patients with UC using MTX for the period
      2001 to 2011. Patients were followed up for 15 months after MTX initiation by
      tracking their prednisone, MTX, thiopurines, and infliximab dispense. Endpoints
      were: (1) successful remission, defined as cessation of prednisone filling
      activity while continuing MTX; (2) failure with continuance, failure to be weaned
      off steroids while continuing MTX; (3) failure with discontinuance, cessation of
      MTX while continuing steroids. RESULTS: We included 91 patients with UC with mean
      age 59 years. The average weekly dose for oral and parenteral MTX was 14 and 25
      mg/week, respectively. The average daily dose for prednisone within the oral MTX
      and parenteral MTX groups was 12 and 25 mg/day, respectively. By the 12th month
      of follow-up, 37% and 30% of patients on oral and parenteral MTX, respectively,
      were able to discontinue steroid. There was a nonsignificant trend toward dose
      reduction of steroids in those who were concomitantly taking oral MTX and
      steroids. CONCLUSIONS: Our study represents the largest cohort of patients with
      MTX and UC reported to date and suggests that approximately one-third of patients
      were successfully weaned off steroids with MTX therapy. MTX should be considered
      in the long-term management of patients with UC on steroids.

PMID- 23542535
TI  - Intrafamilial transmission of hepatitis C infection in Egyptian multitransfused
      thalassemia patients.
AB  - OBJECTIVE: Detecting the current prevalence of hepatitis C virus (HCV) among
      Egyptian multitransfused thalassemic patients and evaluating the risk of its
      transmission within their family members. METHODS: Multitransfused Egyptian
      thalassemia patients (n = 137) were tested for HCV infection. Household contacts
      of positive members were compared with household contacts of HCV-negative
      patients. Antibodies to HCV were detected by enzyme immunoassay. Antibody
      positive cases were retested for viral load using reverse transcriptase
      polymerase chain reaction. HCV genotyping was performed on positive samples of
      the patients and the positive household contacts. RESULTS: In all, 34.4% of
      patients (n = 47) were positive for HCV antibodies and RNA. The study of 24
      families of HCV-positive patients showed 14 affected family members (19.2%). In
      27 families of HCV-negative patients, four family members were affected (4.9%).
      HCV genotyping of seven families was similar in both patients and their family
      members. CONCLUSION: Our results support the role of intrafamilial transmission
      in the spread of HCV.

PMID- 23542536
TI  - Bis(monoacylglycero)phosphate reduces oxysterol formation and apoptosis in
      macrophages exposed to oxidized LDL.
AB  - Atherosclerosis is a major cardiovascular complication of diseases associated
      with increased oxidative stress that favors oxidation of circulating low density
      lipoproteins (LDLs). Oxidized LDL (oxLDL) is considered as highly atherogenic as
      it induces a strong accumulation of cholesterol in subendothelial macrophages
      leading to the formation of foam cells and emergence of atherosclerotic plaque.
      OxLDL is enriched in oxidation products of cholesterol called oxysterols, some of
      which have been involved in the ability of oxLDL to induce cellular oxidative
      stress and cytotoxicity, mainly by apoptosis. Little is known about the possible
      contribution of cell-generated oxysterols toward LDL-associated oxysterols in
      cellular accumulation of oxysterols and related apoptosis. Using both
      radiochemical and mass analyzes, we showed that oxLDL greatly enhanced oxysterol
      production by RAW macrophages in comparison with unloaded cells or cells loaded
      with native LDL. Most oxysterols were produced by non-enzymatic routes (7
      ketocholesterol and 7alpha/beta-hydroyxycholesterol) but enzymatically formed
      7alpha-, 25- and 27-hydroxycholesterol were also quantified.
      Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid preferentially found
      in late endosomes. We and others have highlighted the role of BMP in the
      regulation of intracellular cholesterol metabolism/traffic in macrophages. We
      here report that cellular BMP accumulation was associated with a significantly
      lower production of oxysterols upon oxLDL exposure. Of note, potent pro-apoptotic
      7-ketocholesterol was the most markedly decreased. OxLDL-induced cell
      cytotoxicity and apoptosis were consistently attenuated in BMP-enriched cells.
      Taken together, our data suggest that BMP exerts a protective action against the
      pro-apoptotic effect of oxLDL via a reduced production of intracellular pro
      apoptotic oxysterols.

PMID- 23542537
TI  - The liver X receptor: a master regulator of the gut-liver axis and a target for
      non alcoholic fatty liver disease.
AB  - Since it is associated to the obesity epidemic, non alcoholic fatty liver disease
      (NAFLD) has become a major public health issue. NAFLD ranges from benign hepatic
      steatosis, i.e. abnormally elevated triglyceride accumulation, to non alcoholic
      steatohepatitis (NASH) that can lead to irreversible liver damages. The search
      for pharmacological and dietary approaches to treat or prevent NAFLD has pointed
      at nuclear receptors as sensible targets. Indeed, nuclear receptors are ligand
      sensitive transcription factors that play a central role in hepatic lipid
      metabolism. Among nuclear receptors, the liver X receptor has been identified as
      an oxysterol receptor. It is involved in the control of various aspects of lipid
      metabolism that are reviewed in this manuscript. We highlight the role of LXR in
      the gut-liver axis and the studies that have provided a rationale for strategies
      specifically targeting the hepatic activity of LXR in NAFLD.

PMID- 23542538
TI  - Utility and safety of prolonged video-EEG monitoring in a tertiary pediatric
      epilepsy monitoring unit.
AB  - Prolonged video-EEG (vEEG) monitoring helps characterize paroxysmal events and
      epilepsy. There is limited literature in pediatrics describing the safety and
      utility of vEEG. We retrospectively reviewed 454 pediatric epilepsy monitoring
      unit admissions over two years. Final event diagnoses, duration of seizures, and
      medical complications were analyzed. Two hundred twenty admissions (48.4%)
      captured epileptic seizures, 150 (33.0%) captured nonepileptic events, and 84
      (18.5%) failed to capture any events. Medical complications were seen in 4
      patients (1.8%) with no long-term complications. Seventeen episodes of status
      epilepticus occurred in 13 patients. This constituted 2.9% of all admissions and
      5.9% of admissions with epileptic seizures. The median duration of status was 26
      min, and three patients required transfer to the pediatric intensive care unit.
      Video-EEG monitoring had a high yield in capturing events and differentiating
      epileptic from nonepileptic events. Our pediatric patients experienced greater
      risk of status epilepticus but lesser risk of injury.

PMID- 23542539
TI  - A unified approach for detection of induced epileptic seizures in rats using ECoG
      signals.
AB  - OBJECTIVE: Epileptic seizure detection is a key step for epilepsy assessment. In
      this work, using the pentylenetetrazole (PTZ) model, seizures were induced in
      rats, and ECoG signals in interictal, preictal, ictal, and postictal periods were
      recorded. The recorded ECoG signals were then analyzed to detect epileptic
      seizures in the epileptic rats. METHODS: Two different approaches were considered
      in this work: thresholding and classification. In the thresholding approach, a
      feature is calculated in consecutive windows, and the resulted index is tracked
      over time and compared with a threshold. The moment the index crosses the
      threshold is considered as the moment of seizure onset. In the classification
      approach, features are extracted from before, during, and after ictal periods and
      statistically analyzed. Statistical characteristics of some features have a
      significant difference among these periods, thus resulting in epileptic seizure
      detection. RESULTS: Several features were examined in the thresholding approach.
      Nonlinear energy and coastline features were successful in epileptic seizure
      detection. The best result was achieved by the coastline feature, which led to a
      mean of a 2-second delay in its correct detections. In the classification
      approach, the best result was achieved using the fuzzy similarity index that led
      to Pvalue<0.001. CONCLUSION: This study showed that variance-based features were
      more appropriate for tracking abrupt changes in ECoG signals. Therefore, these
      features perform better in seizure onset estimation, whereas nonlinear features
      or indices, which are based on dynamical systems, can better track the transition
      of neural system to ictal period. SIGNIFICANCE: This paper presents examination
      of different features and indices for detection of induced epileptic seizures
      from rat's ECoG signals.

PMID- 23542540
TI  - A range of antiepileptic drugs do not affect the recovery of consciousness in
      vegetative and minimally conscious states.
AB  - Since most antiepileptic drugs (AEDs) have cognitive effects, the aim of this
      study was to evaluate the influence of AED therapy on the recovery of
      consciousness in 103 consecutive patients in a vegetative or minimally conscious
      state (VS, MCS). The levels of cognitive functioning (LCF) score was
      retrospectively compared after a three-month period of rehabilitation between
      patients who were medicated (n=54) and patients who were not medicated (n=49)
      with AEDs. Mean LCF scores in AED-medicated and nonmedicated patients were 2.2+/
      0.7 and 2.3+/-0.8 at admission and 3.8+/-2.2 and 3.7+/-2.1 after three months,
      respectively (p values>0.05). These results did not change when we compared
      patients with the same etiology separately, with the same disorder of
      consciousness only, or patients treated with only one or more than one AED. In
      conclusion, AEDs did not affect the recovery of consciousness in a large cohort
      of patients in a VS or MCS following an acute brain injury.

PMID- 23542541
TI  - Proper name retrieval in temporal lobe epilepsy: naming of famous faces and
      landmarks.
AB  - The objective of this study was to further explore proper name (PN) retrieval and
      conceptual knowledge in patients with left and right temporal lobe epilepsy (69
      patients with LTLE and 62 patients with RTLE) using a refined assessment
      procedure. Based on the performance of a large group of age- and education
      matched normals, a new test of famous faces and famous landmarks was designed.
      Recognition, naming, and semantic knowledge were assessed consecutively, allowing
      for a better characterization of deficient levels in the naming system.
      Impairment in PN retrieval was common in the cohort with TLE. Furthermore, side
      of seizure onset impaired stages of name retrieval differently: LTLE impaired the
      lexico-phonological processing, whereas RTLE mainly impaired the perceptual
      semantic stage of object recognition. In addition to deficient PN retrieval,
      patients with TLE had reduced conceptual knowledge regarding famous persons and
      landmarks.

PMID- 23542542
TI  - Adolescent sleep misalignment: a chronic jet lag and a matter of public health.
AB  - Sleep is a key element, both physiologically and psychologically, in adolescent
      development. The prevalence of sleep disorders in western countries is important,
      as with age the sleep-wake cycle of adolescents becomes irregular and delayed in
      relation with later sleep onset and waking time resulting in rhythm
      desynchronization. A large number of adolescents sleep for 7-8h instead of 9-10h
      per night, which can lead to a cumulative sleep debt with fatigue, behavioral
      problems and poor academic achievement. The effect of electronic media use (such
      as television, mobile phone, computer, and electronic gaming) on sleep has been
      the object of several international studies, though pubertal changes may also
      impact adolescent sleep. Adolescents and their parents should be educated by
      professionals, including physicians and nurses, on the key role of sleep in
      adolescent well being and quality of life. A number of basic rules are proposed
      to improve sleep in adolescents. The permanent social jet lag experienced by a
      number of adolescents should be considered as a matter of public health. 

PMID- 23542543
TI  - Biological and psychological rhythms: an integrative approach to rhythm
      disturbances in autistic disorder.
AB  - Biological rhythms are crucial phenomena that are perfect examples of the
      adaptation of organisms to their environment. A considerable amount of work has
      described different types of biological rhythms (from circadian to ultradian),
      individual differences in their patterns and the complexity of their regulation.
      In particular, the regulation and maturation of the sleep-wake cycle have been
      thoroughly studied. Its desynchronization, both endogenous and exogenous, is now
      well understood, as are its consequences for cognitive impairments and health
      problems. From a completely different perspective, psychoanalysts have shown a
      growing interest in the rhythms of psychic life. This interest extends beyond the
      original focus of psychoanalysis on dreams and the sleep-wake cycle,
      incorporating central theoretical and practical psychoanalytic issues related to
      the core functioning of the psychic life: the rhythmic structures of drive
      dynamics, intersubjective developmental processes and psychic containment
      functions. Psychopathological and biological approaches to the study of infantile
      autism reveal the importance of specific biological and psychological rhythmic
      disturbances in this disorder. Considering data and hypotheses from both
      perspectives, this paper proposes an integrative approach to the study of these
      rhythmic disturbances and offers an etiopathogenic hypothesis based on this
      integrative approach. 

PMID- 23542544
TI  - Reconsideration of bipolar disorder as a developmental disorder: importance of
      the time of onset.
AB  - Bipolar disorder is a multifactorial psychiatric disorder with developmental and
      progressive neurophysiological alterations. This disorder is typically
      characterized by cyclical and recurrent episodes of mania and depression but is
      heterogeneous in its clinical presentation and outcome. Although the DSM-IV-TR
      criteria identify several features that are of phenomenological relevance, these
      are of less utility for defining homogeneous subgroups, for analyses of
      correlations with biomarkers or for directing focused medication strategies. We
      provide a comprehensive review of existing evidence regarding to age at onset in
      bipolar disorder. Eight admixture studies demonstrate three homogeneous subgroups
      of patients with bipolar disorder identified according to age at onset (early,
      intermediate and late age at onset), with two cutoff points, at 21 and 34 years.
      It is suggested that the early-onset subgroup has specific clinical features and
      outcomes different from those of the other subgroups. Early-onset subgroup may be
      considered a more suitable clinical phenotype for the identification of
      susceptibility genes with recent data demonstrating associations with genetic
      variants specifically in this subgroup. The use of age at onset as a specifier
      may also facilitate the identification of other biological markers for use in
      brain imaging, circadian, inflammatory and cognitive research. A key challenge is
      posed by the use of age at onset in treatment decision algorithms, although
      further research is required to increase the evidence-base. We discuss three
      potential benefits of specifying age at onset, namely: focused medication
      strategies, the targeted prevention of specific comorbid conditions and
      decreasing the duration of untreated illness. We argue that age at onset should
      be included as a specifier for bipolar disorders.

PMID- 23542545
TI  - Rhythms, rhythmicity and aggression.
AB  - The relationships between biological rhythms and human aggressive behavior are
      addressed and discussed in this article: First, circadian rhythms and aggression
      are considered. Studies of sleep/waking cycle disturbances in aggression are
      reported. Severe aggression is associated with profound changes in sleep
      architecture. Causal link is difficult to establish given that sleep disturbance
      and aggressive behavior could be the symptoms of the same disorder. Specific
      aggressive behavior developed during sleep is also described. In addition,
      hormonal circadian rhythm studies are reported. Thus, low cortisol levels, in
      particular low cortisol variability, are associated with aggressive behavior,
      suggesting an inhibitory role of cortisol. Testosterone has daily and seasonal
      fluctuations, but no link with aggression has been established.
      Neurophysiological underlying mechanisms are discussed in the last part of this
      article, with a focus on the relationship between brain rhythm and aggression.
      Increase of slow-wave EEG activities is observed in individuals with aggressive
      behavior. Epilepsy, as a disease of brain rhythm could be associated with
      aggressive behavior, in pre, post and inter ictal periodes. Incidence of
      aggression is not likely more prevalent in epileptic individuals compared to
      those with other neurological conditions. Ictal changes take the form of profound
      behavioral changes, including aggressive behavior which has been interpreted as
      the emergence of "archeical" or innate motor patterns. In this multidisciplinary
      approach, the main difficulty is the categorization of the differents types of
      aggression. Finally, taken together, these studies suggest that biological
      rhythms, especially circadian rhythms, could provide therapeutic benefits to
      human aggressive behavior. Biological rhythymicity seems to be a necessary
      permanent training offering interesting perspectives for the adaptation to
      changes in the field of aggression. 

PMID- 23542546
TI  - Time perception, emotions and mood disorders.
AB  - In this review, we describe recent internal clock models accounting for time
      perception and look at how they try to explain the time distortions produced by
      emotion. We then discuss the results of studies of patients suffering from
      affective disorders (depression) who experience the feeling of time slowing down.
      A distinction is thus made between time perception and explicit awareness of the
      passage of time. We conclude that the feeling that time is passing slowly is not
      systematically associated with a disruption in the basic mechanisms underlying
      time perception. 

PMID- 23542547
TI  - "Disorganized in time": impact of bottom-up and top-down negative emotion
      generation on memory formation among healthy and traumatized adolescents.
AB  - "Travelling in time," a central feature of episodic memory is severely affected
      among individuals with Post Traumatic Stress Disorder (PTSD) with two opposite
      effects: vivid traumatic memories are unorganized in temporality (bottom-up
      processes), non-traumatic personal memories tend to lack spatio-temporal details
      and false recognitions occur more frequently that in the general population (top
      down processes). To test the effect of these two types of processes (i.e. bottom
      up and top-down) on emotional memory, we conducted two studies in healthy and
      traumatized adolescents, a period of life in which vulnerability to emotion is
      particularly high. Using negative and neutral images selected from the
      international affective picture system (IAPS), stimuli were divided into
      perceptual images (emotion generated by perceptual details) and conceptual images
      (emotion generated by the general meaning of the material). Both categories of
      stimuli were then used, along with neutral pictures, in a memory task with two
      phases (encoding and recognition). In both populations, we reported a
      differential effect of the emotional material on encoding and recognition.
      Negative perceptual scenes induced an attentional capture effect during encoding
      and enhanced the recollective distinctiveness. Conversely, the encoding of
      conceptual scenes was similar to neutral ones, but the conceptual relatedness
      induced false memories at retrieval. However, among individuals with PTSD, two
      subgroups of patients were identified. The first subgroup processed the scenes
      faster than controls, except for the perceptual scenes, and obtained similar
      performances to controls in the recognition task. The second subgroup group
      desmonstrated an attentional deficit in the encoding task with no benefit from
      the distinctiveness associated with negative perceptual scenes on memory
      performances. These findings provide a new perspective on how negative emotional
      information may have opposite influences on memory in normal and traumatized
      individuals. It also gives clues to understand how intrusive memories and
      overgeneralization takes place in PTSD. 

PMID- 23542548
TI  - Temporality, trauma and care of repeat adolescent offenders.
AB  - In recent years the matter of repeat young offenders has raised questions for and
      bewildered the institutions caring for them. The temporality of these youngsters
      is ingrained in the current and urgent moment, and in the repetition of acts of
      delinquency, which preclude them from having a linear perception of time. This
      study reflects on the different temporalities with which institutions need to
      work and on how the judicial, educational, and psychological times can, by
      building bridges between the present and the past, help piece together the story
      of adolescents' lives. The personal history of each young offender contributes to
      explain his/her misbehavior. Acting out can symbolize childhood abuse. Thus,
      repetitive acts of delinquency should not be considered and treated as isolated
      acts of violence, which each time cause a rupture, but should be seen and as a
      whole. Repetition of acts of delinquency should prompt questioning about the past
      of young offenders-a past which is buried and which distorts their perception of
      present time, preventing them from projecting themselves into and making plans
      for the future. 

PMID- 23542549
TI  - Anorexia nervosa during adolescence and young adulthood: towards a developmental
      and integrative approach sensitive to time course.
AB  - Anorexia nervosa is situated at the junction between two time scales, the time
      scale of adolescence, in which intense physiological and psychological upheavals
      are occurring over a relatively short period of time, and the time scale of the
      potentially chronic evolution of the disease over the course of the patient's
      lifespan. This second time scale links the critical period of adolescence with
      the pre-morbid period, during which a complex state of vulnerability, often
      unseen and unheard, combines with different risk factors, which may be isolated,
      associated, dissociated or concomitant, to produce the emergence of anorexia; it
      ushers also adolescence into the period of adulthood, flagged with the
      reorganization that occurs in the course of the healing process (in case of
      recovery), or pervaded by somatic and mental distress (in cases where the
      condition becomes chronic). Given the lifespan nature of the disease, it is
      difficult to differentiate premorbid pathogenic factors from changes resulting
      from the acute or chronic phases of the illness. It is also difficult to
      establish straightforward correlations between physiological disturbances and
      their clinical consequences, or conversely to assume that the restoration of
      physiological parameters means the disappearance of the underlying mental
      disorder. Taken together, these observations support an approach to anorexia
      nervosa that is both developmental and integrative, taking into account both the
      complexity of the pathways involved and the developmental timescales of these
      pathways. This type of approach can help to adjust therapeutic strategies and
      thus enhance prognosis, in particular by integrating the temporal parameter into
      the dynamics of care plans. 

PMID- 23542550
TI  - Rhythmicity in infants' experiences and their development.
AB  - This article deals with the importance of rhythm in infants' experiences,
      underscoring its function in relation to sense of being and the continuity of
      that sense. Although some discontinuity is inevitable, and indeed necessary for
      development, it can expose infants to chaotic experiences if there is no
      underlying rhythmicity. Observations of infants have highlighted their ability to
      manage their experiences of discontinuity (providing these are not too
      disorganizing) by finding supports and manufacturing a rhythmicity that enables
      them to remain open to self and to the world. Rhythmicity of experience is
      important not just in infant development, but also - and more generally - in
      learning contexts and psychological care settings. In every situation, external
      rhythms must be attuned to the individual's inner one. 

PMID- 23542551
TI  - Using zebrafish transgenesis to test human genomic sequences for specific
      enhancer activity.
AB  - We detail an approach for the identification of human tissue-specific
      transcriptional enhancers involving three steps: delineation of search space
      around a locus or target gene, in silico identification and size definition of
      putative candidate sequences, and testing through several independent genomic
      insertions in a transgenic zebrafish reporter assay. Candidate sequences are
      defined through evolutionary conservation, transcription factor binding and
      chromatin marks (e.g. ENCODE data) and are amplified from genomic DNA, cloned
      into basal promoter:fluorescent protein reporter vectors based on the Tol2
      transposon system and are microinjected into fertilized zebrafish eggs. After
      raising injected founders to sexual maturity, fluorescent screening identifies
      positive founder fish whose offspring undergo a detailed expression analysis to
      determine tissue specificity and reproducibility of specific enhancers. 

PMID- 23542552
TI  - The nitroreductase system of inducible targeted ablation facilitates cell
      specific regenerative studies in zebrafish.
AB  - At the turn of the 20th century, classical regenerative biology--the study of
      organismal/tissue/limb regeneration in animals such as crayfish, snails, and
      planaria--garnered much attention. However, scientific luminaries such as Thomas
      Hunt Morgan eventually turned to other fields after concluding that inquiries
      into regenerative mechanisms were largely intractable beyond observational
      intrigues. The field of regeneration has enjoyed a resurgence in research
      activity at the turn of the 21st century, in large part due to "the promise" of
      cultured stem cells regarding reparative therapeutic approaches. Additionally,
      genomics-based methods that allow sophisticated genetic/molecular manipulations
      to be carried out in nearly any species have extended organismal regenerative
      biology well beyond observational limits. Throughout its history, complex
      paradigms such as limb regeneration--involving multiple tissue/cell types, thus,
      potentially multiple stem cell subtypes--have predominated the regenerative
      biology field. Conversely, cellular regeneration--the replacement of specific
      cell types--has been studied from only a few perspectives (predominantly muscle
      and mechanosensory hair cells). Yet, many of the degenerative diseases that
      regenerative biology hopes to address involve the loss of individual cell types;
      thus, a primary emphasis of the embryonic/induced stem cell field is defining
      culture conditions which promote cell-specific differentiation. Here we will
      discuss recent methodological approaches that promote the study of cell-specific
      regeneration. Such paradigms can reveal how the differentiation of specific cell
      types and regenerative potential of discrete stem cell niches are regulated. In
      particular, we will focus on how the nitroreductase (NTR) system of inducible
      targeted cell ablation facilitates: (1) large-scale genetic and chemical screens
      for identifying factors that regulate regeneration and (2) in vivo time-lapse
      imaging experiments aimed at investigating regenerative processes more directly.
      Combining powerful screening and imaging technologies with targeted ablation
      systems can expand our understanding of how individual stem cell niches are
      regulated. The former approach promotes the development of therapies aimed at
      enhancing regenerative potentials in humans, the latter facilitates investigation
      of phenomena that are otherwise difficult to resolve, such as the role of
      cellular transdifferentiation or the innate immune system in regenerative
      paradigms.

PMID- 23542553
TI  - Parent perceptions of children's hospital safety climate.
AB  - BACKGROUND: Because patients are at the frontline of care where safety climate is
      closely tied to safety events, understanding patient perceptions of safety
      climate is crucial. We sought to develop and evaluate a parent-reported version
      of the Agency for Healthcare Research and Quality Hospital Survey on Patient
      Safety Culture and to relate parent-reported responses to parental need to watch
      over their child's care to ensure mistakes are not made. METHODS: Parents (n=172)
      were surveyed about perceptions of hospital safety climate (14 items representing
      four domains-overall perceptions of safety, openness of staff and parent
      communication, and handoffs and transitions) and perceived need to watch over
      their child's care. Confirmatory factor analysis (CFA) was used to validate
      safety climate domain measures. Logistic regression was used to relate need to
      watch over care to safety climate domains. RESULTS: CFA indices suggested good
      model fit for safety climate domains. Thirty-nine per cent of parents agreed or
      strongly agreed they needed to watch over care. In adjusted models, need to watch
      over care was significantly related to overall perceptions of safety (OR 0.20,
      95% CI 0.11 to 0.37) and to handoffs and transitions (0.25, 0.14 to 0.46), but
      not to openness of staff (0.67, 0.40 to 1.12) or parent (0.83, 0.48 to 1.45)
      communication. CONCLUSIONS: Findings suggest parents can provide valuable data on
      specific safety climate domains. Opportunities exist to improve our safety
      climate's impact on parent burden to watch over their child's care, such as
      targeting overall perceptions of safety as well as handoffs and transitions.

PMID- 23542554
TI  - In vitro and in vivo evaluation of biodegradable, open-porous scaffolds made of
      sintered magnesium W4 short fibres.
AB  - A cytocompatible and biocompatible, degradable, open-porous, mechanically
      adaptable metal scaffold made of magnesium alloy W4 melt-extracted short fibres
      was fabricated by liquid phase sintering. Cylindrical samples (3*5 mm) of
      sintered W4 short fibres were evaluated under in vitro (L929, HOB, eudiometer,
      weight loss) and in vivo conditions (rabbits: 6 and 12 weeks). The in vitro
      corrosion environment (e.g., temperature, flow, composition of corrosion
      solution, exposure time) significantly influenced the corrosion rates of W4
      scaffolds compared with corrosion in vivo. Corrosion rates under cell culture
      conditions for 72 h varied from 1.05 to 3.43 mm y(-1) depending on the media
      composition. Corrosion rates measured in eudiometric systems for 24 h were ~24-27
      times higher (3.88-4.43 mm y(-1)) than corrosion in vivo after 6 weeks (0.16 mm
      y(-1)). Moreover, it was found that the cell culture media composition
      significantly influences the ionic composition of the extract by selectively
      dissolving ions from W4 samples or their corrosion products. A pilot in vivo
      study for 6 and 12 weeks demonstrated active bone remodelling, no foreign body
      reaction and no clinical observation of gas formation during W4 scaffold
      implantation. Long-term in vivo studies need to be conducted to prove complete
      degradation of the W4 scaffold and total replacement by the host tissue.

PMID- 23542555
TI  - LaB6 nanoparticles with carbon-doped silica coating for fluorescence imaging and
      near-IR photothermal therapy of cancer cells.
AB  - In this study, LaB6 nanoparticles are used as a novel nanomaterial for near
      infrared (NIR) photothermal therapy because they are cheaper than nanostructured
      gold, are easy to prepare and have an excellent NIR photothermal conversion
      property. Furthermore, the surface of LaB6 nanoparticles is coated with a carbon
      doped silica (C-SiO2) shell to introduce a fluorescent property and improve
      stability and biocompatibility. The resulting LaB6@C-SiO2 nanoparticles retain
      the excellent NIR photothermal conversion property and exhibit a bright blue
      emission under UV irradiation or a green emission under visible irradiation.
      Using a HeLa cancer cell line, it is demonstrated that LaB6@C-SiO2 nanoparticles
      have no significant cytotoxicity, but their presence leads to remarkable cell
      death after NIR irradiation. In addition, from the observation of cellular
      uptake, the fluorescence labeling function of LaB6@SiO2 (LaB6 core/SiO2 shell)
      nanoparticles is also confirmed. These results suggest that LaB6@C-SiO2
      nanoparticles may potentially serve as an efficient multifunctional nano-platform
      for simultaneous fluorescent imaging and NIR-triggered photothermal therapy of
      cancer cells.

PMID- 23542556
TI  - The collagen component of biological bone graft substitutes promotes ectopic bone
      formation by human mesenchymal stem cells.
AB  - Synthetic bone substitutes are attractive materials for repairing a variety of
      bone defects. They are readily available in unlimited quantities, have a defined
      composition without batch variability and bear no risk of disease transmission.
      When combined with mesenchymal stem cells (MSCs), bone healing can be further
      enhanced due to the osteogenic potential of these cells. However, human MSCs
      showed considerable donor variability in ectopic bone formation assays on
      synthetic bone substitutes, which may limit clinical success. This study
      addresses whether bone formation variability of MSCs is cell-intrinsic or
      biomaterial-dependent and may be improved using biological bone substitutes with
      and without collagen. Ectopic bone formation of MSCs from nine donors was tested
      in immune-deficient mice on biological bone substitutes of bovine and equine
      origin, containing collagen (bHA-C; eHA-C) or not (bHA; eHA). Synthetic beta-TCP
      was used for comparison. Histology of 8-week explants demonstrated a significant
      influence of the bone graft substitute (BGS) on donor variability of ectopic bone
      formation with best results seen for eHA-C (15/17) and beta-TCP (16/18). Bone was
      of human origin in all groups according to species-specific in situ
      hybridization, but MSCs from one donor formed no bone with any bone substitute.
      According to histomorphometry, most neo-bone was formed on eHA-C with significant
      differences to bHA, eHA and beta-TCP (p<0.001). Collagen-free biological BGSs
      were inferior to biological BGSs with collagen (p<0.001), while species-origin
      was of little influence. In conclusion, BGS composition had a strong influence on
      ectopic bone formation ability of MSCs, and biological BGSs with a collagen
      component seem most promising to display the strong osteogenic potential of MSCs.

PMID- 23542557
TI  - Quality of life following endoscopic resection of skull base tumors.
AB  - The objective of the study is to evaluate patients' quality of life (QOL) after
      endoscopic resection of skull base tumors. We estimated the QOL of 41 patients
      who underwent surgery for removal of skull base tumors via the expanded endonasal
      approach (EEA). The Anterior Skull Base Surgery Questionnaire (ASBS-Q), a
      multidimensional, disease-specific instrument containing 36 items was used. The
      rate of meningitis and cerebrospinal fluid leak was 1.4 and 0%, respectively.
      There was one case of uniocular visual impairment. The internal consistency of
      the instrument had a correlation coefficient (alpha-Cronbach score) of 0.8 to
      0.92. Of 41 patients, 30 (75%) reported improvement or no change in overall QOL.
      Improved scores were reported in the physical function domain and worse scores in
      the specific symptoms domain. The most significant predictor of poor QOL was
      female gender, which led to a significant decrease in scores of all domains. Site
      of surgery, histology, age and comorbidity were not significant predictors of
      outcome. This paper further validates the use of the ASBS-Q for patients
      undergoing endoscopic skull base resection. The overall QOL of patients following
      endoscopic extirpation of skull base tumors is good. Female patients experience a
      significant decline in QOL compared with males.

PMID- 23542558
TI  - Tilt testing with combined lower body negative pressure: a "gold standard" for
      measuring orthostatic tolerance.
AB  - Orthostatic tolerance (OT) refers to the ability to maintain cardiovascular
      stability when upright, against the hydrostatic effects of gravity, and hence to
      maintain cerebral perfusion and prevent syncope (fainting). Various techniques
      are available to assess OT and the effects of gravitational stress upon the
      circulation, typically by reproducing a presyncopal event (near-fainting episode)
      in a controlled laboratory environment. The time and/or degree of stress required
      to provoke this response provides the measure of OT. Any technique used to
      determine OT should: enable distinction between patients with orthostatic
      intolerance (of various causes) and asymptomatic control subjects; be highly
      reproducible, enabling evaluation of therapeutic interventions; avoid invasive
      procedures, which are known to impair OT(1). In the late 1980s head-upright tilt
      testing was first utilized for diagnosing syncope(2). Since then it has been used
      to assess OT in patients with syncope of unknown cause, as well as in healthy
      subjects to study postural cardiovascular reflexes(2-6). Tilting protocols
      comprise three categories: passive tilt; passive tilt accompanied by
      pharmacological provocation; and passive tilt with combined lower body negative
      pressure (LBNP). However, the effects of tilt testing (and other orthostatic
      stress testing modalities) are often poorly reproducible, with low sensitivity
      and specificity to diagnose orthostatic intolerance(7). Typically, a passive tilt
      includes 20-60 min of orthostatic stress continued until the onset of presyncope
      in patients(2-6). However, the main drawback of this procedure is its inability
      to invoke presyncope in all individuals undergoing the test, and corresponding
      low sensitivity(8,9). Thus, different methods were explored to increase the
      orthostatic stress and improve sensitivity. Pharmacological provocation has been
      used to increase the orthostatic challenge, for example using
      isoprenaline(4,7,10,11) or sublingual nitrate(12,13). However, the main drawback
      of these approaches are increases in sensitivity at the cost of unacceptable
      decreases in specificity(10,14), with a high positive response rate immediately
      after administration(15). Furthermore, invasive procedures associated with some
      pharmacological provocations greatly increase the false positive rate(1). Another
      approach is to combine passive tilt testing with LBNP, providing a stronger
      orthostatic stress without invasive procedures or drug side-effects, using the
      technique pioneered by Professor Roger Hainsworth in the 1990s(16-18). This
      approach provokes presyncope in almost all subjects (allowing for symptom
      recognition in patients with syncope), while discriminating between patients with
      syncope and healthy controls, with a specificity of 92%, sensitivity of 85%, and
      repeatability of 1.1+/-0.6 min(16,17). This allows not only diagnosis and
      pathophysiological assessment(19-22), but also the evaluation of treatments for
      orthostatic intolerance due to its high repeatability(23-30). For these reasons,
      we argue this should be the "gold standard" for orthostatic stress testing, and
      accordingly this will be the method described in this paper.

PMID- 23542559
TI  - A global toxicogenomic analysis investigating the mechanistic differences between
      tobacco and marijuana smoke condensates in vitro.
AB  - Like tobacco smoking, habitual marijuana smoking causes numerous adverse
      pulmonary effects. However, the mechanisms of action involved, especially as
      compared to tobacco smoke, are still unclear. To uncover putative modes of
      action, this study employed a toxicogenomics approach to compare the
      toxicological pathways perturbed following exposure to marijuana and tobacco
      smoke condensate in vitro. Condensates of mainstream smoke from hand-rolled
      tobacco and marijuana cigarettes were similarly prepared using identical smoking
      conditions. Murine lung epithelial cells were exposed to low, medium and high
      concentrations of the smoke condensates for 6h. RNA was extracted immediately or
      after a 4h recovery period and hybridized to mouse whole genome microarrays.
      Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic
      metabolism, oxidative stress, inflammation, and DNA damage response. These same
      pathways were also significantly affected following marijuana smoke condensate
      (MSC) exposure. Although the effects of the condensates were largely similar,
      dose-response analysis indicates that the MSC is substantially more potent than
      TSC. In addition, steroid biosynthesis, apoptosis, and inflammation pathways were
      more significantly affected following MSC exposure, whereas M phase cell cycle
      pathways were more significantly affected following TSC exposure. MSC exposure
      also appeared to elicit more severe oxidative stress than TSC exposure, which may
      account for the greater cytotoxicity of MSC. This study shows that in general MSC
      impacts many of the same molecular processes as TSC. However, subtle pathway
      differences can provide insight into the differential toxicities of the two
      complex mixtures.

PMID- 23542560
TI  - Editorial: molecular endocrinology articles in the spotlight for April 2013.

PMID- 23542562
TI  - Moving forward on shifting sands: ethical regulation of gene therapy clinical
      trials in the United kingdom.

PMID- 23542565
TI  - A crisper look at genome editing: RNA-guided genome modification.

PMID- 23542566
TI  - "Infectious" optimism for treatment of hepatocellular carcinoma.

PMID- 23542568
TI  - Real-time estimation of TP load in a Mississippi Delta stream using a dynamic
      data driven application system.
AB  - Elevated phosphorus (P) in surface waters can cause eutrophication of aquatic
      ecosystems and can impair water for drinking, industry, agriculture, and
      recreation. Currently, no effort has been devoted to estimating real-time
      variation and load of total P (TP) in surface waters due to the lack of suitable
      and/or cost-effective wireless sensors. However, when considering human health,
      drinking water supply, and rapidly developing events such as algal blooms, the
      availability of timely P information is very critical. In this study, we
      developed a new approach in the form of a dynamic data driven application system
      (DDDAS) for monitoring the real-time variation and load of TP in surface water.
      This DDDAS consisted of the following three major components: (1) a User Control
      that interacts with Schedule Run to implement the DDDAS with starting and ending
      times; (2) a Schedule Run that activates the Hydstra model; and (3) a Hydstra
      model that downloads the real-time data from a US Geological Survey (USGS)
      website that is updated every 15 min with data from USGS monitoring stations,
      predicts real-time variation and load of TP, graphs the variables in real-time on
      a computer screen, and sends email alerts when the TP exceeds a certain value.
      The DDDAS was applied to monitor real-time variation and load of TP for 30 days
      in Deer Creek, a stream located east of Leland, Mississippi, USA. Results showed
      that the TP concentrations in the stream ranged from 0.24 to 0.48 mg L(-1) with
      an average of 0.30 mg L(-1) for a 30-day monitoring period, whereas the
      cumulative load of TP from the stream was about 2.8 kg for the same monitoring
      period. Our study suggests that the DDDAS developed in this study was useful for
      estimating the real-time variation and load of TP in surface water ecosystems.

PMID- 23542569
TI  - Factors affecting chelating extraction of Cr, Cu, and As from CCA-treated wood.
AB  - The disposal of chromated copper arsenate (CCA)-treated waste wood is becoming a
      serious problem in many countries due to potential leaching of hazardous elements
      from in-service use in the environment or disposal of solutions after
      remediation; therefore, it is necessary to develop proper remediation techniques.
      The effects of concentration, extraction period, temperature, and sequential
      extraction on the extraction of Cr, Cu, and As from CCA-treated wood using [S,S]
      ethylenediaminedisuccinic acid (EDDS), ethylenediaminetetraacetic acid (EDTA),
      and nitrilotriacetic acid (NTA) were studied. Mobility of metal in the samples
      was evaluated by using a sequential extraction scheme that could give the
      information needed to explain different extraction efficiencies for different
      metals. Results of long-term leaching tests of CCA-treated wood before and after
      EDDS extraction were used to evaluate Cr, Cu, and As leachability. Kinetic
      experiments showed that 6 h was the optimum extraction time for all metals and
      CCA-treated wood. Experimental results showed that EDDS is a very effective
      chelating agent for the extraction of Cr, Cu, and As from CCA-treated wood.
      Increased temperature significantly enhanced the extraction efficiency of CCA
      metals, especially Cr and As. The much better extractability of Cu compared to Cr
      and As by chelating agents can be attributed to the presence of larger weakly
      bound fractions. The CCA-treated woods after EDDS extraction have met the EPA's
      TCLP regulatory limit and could be classified as a non-hazardous waste according
      to identification standard of hazardous wastes.

PMID- 23542570
TI  - Serum carbohydrate deficient transferrin as a sensitive marker in diagnosing
      alcohol abuse: a case - control study.
AB  - BACKGROUND: Alcoholism is a major problem in India thereby causing a heavy toll
      on the health related expenditure of the country. Detection of alcohol abuse rely
      mainly on clinical details which is sometimes inaccurate or unreliable and hence
      using a specific diagnostic parameter might be of immense use not only for early
      diagnosis but also during follow up of the cases. AIMS AND OBJECTIVES: This case
      control study aimed at evaluating the usefulness of Carbohydrate Deficient
      Transferrin (CDT) as a sensitive marker to diagnose alcohol abuse. MATERIALS AND
      METHODS: The study was approved by Institutional research and ethical committee.
      Twenty five known male alcoholics who attended to the OPD (Out Patient
      Department) of Alcohol de-addiction centre of a tertiary care hospital were
      selected as cases. All of them were diagnosed to have a strong likely hood of
      hazardous alcohol consumption based on 'Alcohol Use Disorders Identification
      Test" (AUDIT) questionnaire. Twenty five age matched, gender matched healthy
      individuals who were teetotalers were selected as controls. They scored zero in
      AUDIT questionnaire. Informed consent was obtained from all the cases and
      controls. The following tests were done: Liver function tests including Serum
      Bilirubin, Total Proteins, Aspartate Amino Transferase (AST), Alanine Amino
      Transferase (ALT), Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT)
      and Blood glucose levels were estimated using a fully automated biochemistry
      analyser, XL - 300 (Trans Asia Biomedical systems) and Mean Corpuscular Volume
      (MCV) was done using an automated hematology analyser Sysmex KX-21. Percentage of
      Serum Carbohydrate Deficient Transferrin (%CDT) was assessed using immuno
      Turbidimetric assay, ELISA method (iMark, Bio-Rad Laboratories,). Statistical
      analysis of the data obtained was done using SPSS 16.0. RESULTS: There was a
      statistically significant difference in values of AST, ALT, ALP, MCV, GGT and %
      CDT in cases as compared to controls. ROC curves drawn to assess the sensitivity
      and specificity of each parameter showed that %CDT has the highest sensitivity
      and specificity (84% and 92% respectively) and MCV (48% and 52% respectively) had
      the least. GGT when compared to % CDT had a lower sensitivity and specificity
      (64% and 72% respectively). CONCLUSION: % CDT is a sensitive biomarker which can
      be used to diagnose alcohol abuse and is superior to GGT in terms of sensitivity
      as well as specificity.

PMID- 23542571
TI  - Deep venous thrombosis in lap band surgery: a single center study.
AB  - Bariatric surgery has been demonstrated to be an effective treatment for morbid
      obesity. The purpose of this study is to investigate the incidence of pre- and
      post-operative deep venous thrombosis (DVT) in Lap-Band surgical patients. This
      study group comprised 56 consecutive patients who underwent Lap-Band surgery.
      Mean age and body mass index were 38 years (range: 18-64 years) and 50.9 kg/m(2)
      (range: 53-74 kg/m(2)), respectively. All the patients were screened with duplex
      ultrasonography pre- and post-operatively. There were no iliac, femoral, or
      popliteal vein thromboses detected at any given point of time. No patient had any
      clinical signs or symptoms of DVT post-operatively. There were no observable
      differences attributable to DVT prophylaxis. This data suggest that in the
      setting of chemical and mechanical prophylaxis, the incidence of DVT in patients
      undergoing Lap-Band surgery at an established bariatric centre is minimal.

PMID- 23542572
TI  - In vitro biotransformation of decabromodiphenyl ether (BDE-209) and Dechlorane
      Plus flame retardants: a case study of ring-billed gull breeding in a pollution
      hotspot in the St. Lawrence River, Canada.
AB  - Decabromodiphenyl ether (deca-BDE) mixture (~97% of BDE-209) is now facing usage
      restrictions worldwide, which is leading to increased utilization of a series of
      alternative, replacement flame retardant (FR) products. Among these, Dechlorane
      Plus (DP) is receiving growing attention as this FR is increasingly being
      detected in wildlife samples, including birds from North America, Europe and
      Asia. Recent survey conducted in a known FR hotspot in the St. Lawrence River
      basin near Montreal (QC, Canada) revealed unexpectedly high detection frequencies
      and concentrations of BDE-209 and DP isomers (syn- and anti-DP) in the liver of
      breeding ring-billed gulls (Larus delawarensis) (RBGUs). Despite the global
      distribution of these current-use FRs, there is to our knowledge no study that
      has addressed the in vitro biotransformation of BDE-209 and DP isomers in birds.
      This study aimed at understanding the in vitro metabolism of BDE-209 and syn- and
      anti-DP using liver microsomes of Montreal-breeding RBGUs. Although BDE-15
      (positive assay control) was consistently and positively depleted over the 90-min
      time frame of the in vitro assay, no depletion was observed for BDE-209 and DP
      isomers. These results suggest that CYP isoenzyme-mediated reductive
      dehalogenation of BDE-209 and DP is not likely to be a substantial metabolic
      pathway in RBGUs. However, investigations on deiodinases (expression, activity)
      should be considered in future studies as these enzymes have been suggested to be
      involved in the sequential debromination of BDE-209 in fish and human studies.
      High levels of BDE-209 determined in liver of RBGUs that strongly correlated with
      those of known or suggested BDE-209 debromination products (hepta- through nona
      BDEs) may thus be indicative of concomitant dietary (e.g., fish consumption) and
      environmental exposure in the greater Montreal area, combined with poor or lack
      of metabolic capability toward these FRs.

PMID- 23542573
TI  - Trigger values for investigation of hormonal activity in drinking water and its
      sources using CALUX bioassays.
AB  - To screen for hormonal activity in water samples, highly sensitive in vitro CALUX
      bioassays are available which allow detection of estrogenic (ERalpha), androgenic
      (AR), progestagenic (PR), and glucocorticoid (GR) activities. This paper presents
      trigger values for the ERalpha, AR, PR, and GR CALUX bioassays for agonistic
      hormonal activities in (drinking) water, which define a level above which human
      health risk cannot be waived a priori and additional examination of specific
      endocrine activity may be warranted. The trigger values are based on 1)
      acceptable or tolerable daily intake (ADI/TDI) values of specific compounds, 2)
      pharmacokinetic factors defining their bioavailability, 3) estimations of the
      bioavailability of unknown compounds with equivalent hormonal activity, 4)
      relative endocrine potencies, and 5) physiological, and drinking water allocation
      factors. As a result, trigger values of 3.8ng 17beta-estradiol (E2)-equivalents
      (eq)/L, 11ng dihydrotestosterone (DHT)-eq/L, 21ng dexamethasone (DEX)-eq/L, and
      333ng Org2058-eq/L were derived. Benchmark Quotient (BQ) values were derived by
      dividing hormonal activity in water samples by the derived trigger using the
      highest concentrations detected in a recent, limited screening of Dutch water
      samples, and were in the order of (value) AR (0.41)>ERalpha (0.13)>GR (0.06)>PR
      (0.04). The application of trigger values derived in the present study can help
      to judge measured agonistic hormonal activities in water samples using the CALUX
      bioassays and help to decide whether further examination of specific endocrine
      activity followed by a subsequent safety evaluation may be warranted, or whether
      concentrations of such activity are of low priority with respect to health
      concerns in the human population. For instance, at one specific drinking water
      production site ERalpha and AR (but no GR and PR) activities were detected in
      drinking water, however, these levels are at least a factor 83 smaller than the
      respective trigger values, and therefore no human health risks are to be expected
      from hormonal activity in Dutch drinking water from this site.

PMID- 23542574
TI  - A cross sectional investigation of malaria epidemiology among seven tea estates
      in Assam, India.
AB  - In the present investigation, the epidemiology of malaria among seven tea estates
      of Nagaon and Udalguri districts of Assam, India has been described. A cross
      sectional open study was carried out to understand the malaria epidemiology and
      associated risk factors among the tea tribes during March to September 2009. Out
      of 1,182 peripheral blood smears examined, 506 found positive for malaria (slide
      positivity rate, SPR = 42.8) with Plasmodium falciparum as predominant species.
      Dimakuchi tea estate was having highest SPR (P = 0.0275) and contributed more
      number of P. falciparum cases (P < 0.00001). Tea estates studied in both Udalguri
      and Nagaon districts were equally affected and the SPR recorded were 41.75 and
      43.32% respectively. 154 malaria cases detected were having 'O' blood group but
      each blood group was found to have similar susceptibility of acquiring malaria
      infection (chi(2 ) = 3.603; P = 0.3076) and P. falciparum infection (chi(2 ) =
      1.818; P = 0.6110). The SPR was highest among children more than 2 years of age
      group and variation in SPR among the age groups was statistically significant
      (chi(2 ) = 17.186; P = 0.0018). No gender biasing was observed in malaria
      distribution. Anemia was found associated with the infection among both the
      sexes. The findings suggest that tea estates are endemic for stable malaria
      transmission primarily due to P. falciparum and the prevalence rate decline with
      age, suggesting the development of protective immunity. Promising intervention
      measures could be able to reduce the malaria prevalence effectively in the study
      areas.

PMID- 23542575
TI  - Free radical status in retinopathy of prematurity.
AB  - Retinopathy of prematurity (ROP) is a major cause of blindness in children. Free
      radicals are implicated in the development of this retinopathy. We studied the
      role of free radicals in ROP and enrolled 60 preterm neonates at 30-32 weeks age.
      Thirty neonates predisposed to development of ROP, were placed in study group and
      30 normal neonates in control group. Malondialdehyde and antioxidant enzymes
      superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in
      blood spectrophotometrically. Both the groups were followed-up to 40-42 weeks
      age. Serum MDA levels, erythrocyte SOD and plasma GPX were significantly high in
      study group at 30-32 weeks as compared to control group. At follow up visit
      significant increase in MDA level and decrease in SOD and GPX level among the
      study group was seen. This disturbance in equilibrium of oxidant and antioxidant
      status initiates an inflammatory process in retinal tissue leading to development
      of ROP.

PMID- 23542576
TI  - Parasitological and clinico-epidemiological features of onchocerciasis in West
      Wellega, Ethiopia.
AB  - Onchocerciasis is a disease of public health and socio-economic importance in
      Ethiopia. The aim of this study was to assess parasitological and clinico
      epidemiological features of onchocerciasis in the Anfilo District, West Wellega,
      prior to implementation of Community Directed Treatment with Ivermectin (CDTI) to
      generate epidemiological and parasitological data for use in control program of
      the disease and subsequent evaluation of CDTI. A cross-sectional study was
      conducted in Anfilo District of West Wellega zone during a period of 1 month:
      from mid-August to mid-September 2006. Data on socio-demographic characteristics
      were collected using a standardized questionnaire prepared for this purpose. All
      persons were examined clinically for skin signs and symptoms of onchocerciasis.
      Two skin snips, one from each side of the gluteal fold were taken using blood
      lancet and sterilized razor blade and examined for microfilaria. All data were
      categorized, coded, entered in a data base and analyzed using SPSS version 15.0.
      for windows. A total of 1114 individuals >=15 years were examined for
      microfilariae (mf) of Onchocerca volvulus and onchocercal skin disease (OSD). The
      prevalence of onchocercal (mf) carrier was 74.8% (833/1114). In both genders, the
      prevalence of onchocerciasis showed direct correlations with the age of
      individuals (R (2) = 0.79, P < 0.05). The infection rate varied with the
      occupation of the study subjects, with preponderance among farmers. Among the
      subjects with onchocerciasis, the mf density ranged from 1.0 to 711.0 per mg of
      skin snip with a mean density (SD) and median values of 32.1 (61.5) and 10.4
      respectively. The overall community microfilariae load (CMFL), the most sensitive
      parasitological indicator of onchocerciasis was 19.6. The pervasiveness of OSD
      among the study subjects was 26.4%. OSD was more frequent in males (32.4%) than
      their female counterparts (20.8%, P < 0.05). The overall prevalence of
      onchocercal nodule carrier, the symptom opted for determining the community-wide
      prevalence of onchocerciasis was 12.1%. Leopard skin, the proxy of longstanding
      infection of onchocerciasis in the community, was also relatively high (19.1%).
      The abundance of mf in skin would definitely lead to high transmission potential
      in the Anfilo District. The situation in the Anfilo District should call for
      continued CDTI, owing to success of similar recommendations for such programmes
      in other parts of the country and elsewhere.

PMID- 23542577
TI  - The Diagnostic Role of the Marginal Vacuoles in FNAC of Solitary Thyroid Nodules.
AB  - CONTEXT: FNAC thyroid is more sensitive as well as specific in segregating
      neoplastic and non-neoplastic thyroid lesions. Identification of predominant cell
      pattern, cell morphology and background details in FNAC smears play an important
      role in categorisation of various thyroid lesions with accuracy. Marginal
      vacuoles (MVs) have been described as irregular cytoplasmic vacuoles with largely
      unstained central area. MVs, although suggestive of thyrotoxicosis, are non
      specific, as they are also encountered in non- toxic goitre, Hashimoto's
      thyroiditis and follicular carcinoma. This cytologic finding therefore deserves
      further study to precisely delineate its utility. Aims & Objective: To
      investigate whether MVs have a diagnostic role in FNAC of solitary thyroid nodule
      Setting & Design: This study was conducted on 40 patients who presented with
      solitary thyroid nodule. METHODS & MATERIAL: Forty patients having solitary
      thyroid nodule were subjected to FNAC on an outpatient basis. Their
      cytomorphological features were studied with special attention to presence of
      MVs. MVs if present were then graded as no/ scant (gradeI ), moderate (gradeII)
      and abundant (gradeIII). RESULTS AND CONCLUSION: Majority (77.5%) of nodular
      goitres had insignificant MVs (gradeI) in their smears. Significant MVs
      (gradeII+III) were limited to autoimmune thyroiditis presenting as solitary
      nodule and follicular neoplasms. Abundant MVs/ gradeIII were seen in follicular
      neoplasm only. MVs were not present in rest of neoplastic goitres. This implies
      that MVs are a marker of follicular differentiation.

PMID- 23542578
TI  - A novel method for preparing complete antigens of gonyautoxin 2,3 and their
      feature of immunogenicity.
AB  - In this paper, a novel method was proposed to prepare artificial antigens of
      gonyaulax parlaytic shellfish toxin 2 and 3 (GTX2,3). An intermediate GTX2,3
      aldehyde was first synthesized by activating the NH2 group of the 2nd and 8th
      amino acid residues with three different aldehydes and two artificial complete
      antigens GTX2,3-aldehyde-bovine serum albumin (BSA) and GTX2,3-aldehyde- keyhole
      limpet hemocyanin (KLH) were then prepared by cross-linking the intermediate with
      BSA or KLH. The successful preparation of the two complete antigens was confirmed
      by UV spectral scanning, HPLC, production of antibodies with titer of 1.28 * 104
      from mice immunized with the two complete antigens, indirect ELISA and Western
      blot. In conclusion, the synthesized complete antigens have strong
      immunogenicity, which provides a solid foundation for preparing GTX2,3 monoclonal
      antibody and rapid detection kit.

PMID- 23542579
TI  - Detection of microRNA as novel biomarkers of epithelial ovarian cancer from the
      serum of ovarian cancer patients.
AB  - OBJECTIVE: MicroRNA (miRNA) is an abundant class of small noncoding RNAs that act
      as gene regulators. Recent studies have suggested that miRNA deregulation is
      associated with the initiation and progression of human cancer. However,
      information about cancer-related miRNA is mostly limited to tissue miRNA. The aim
      of this study was to find specific profiles of serum-derived miRNAs of ovarian
      cancer based on a comparative study using a miRNA microarray of serum, tissue,
      and ascites. METHODS: From 2 ovarian cancer patients and a healthy control, total
      RNA was isolated from their serum, tissue, and ascites, respectively, and
      analyzed by a microarray. Under the comparative study of each miRNA microarray,
      we sorted out several miRNAs showing a consistent regulation tendency throughout
      all 3 specimens and the greatest range of alteration in serum as potential
      biomarkers. The availability of biomarkers was confirmed by qRT-PCR of 18
      patients and 12 controls. RESULTS: Out of 2222 kinds of total miRNAs that were
      identified in the microarray analysis, 95 miRNAs were down-regulated and 88
      miRNAs were up-regulated, in the serum, tissue, and ascites of cancer patients.
      Among the miRNAs that showed a consistent regulation tendency through all
      specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132,
      miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly
      down-regulated miRNAs in the serum from ovarian cancer patients with respect to
      those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5
      selected miRNAs were significantly underexpressed in the serum of ovarian cancer
      patients in qRT-PCR. CONCLUSIONS: Serum miR-132, miR-26a, let-7b, and miR-145
      could be considered as potential candidates as novel biomarkers in serous ovarian
      cancer. Also, serum miRNAs is a promising and useful tool for discriminating
      between controls and patients with serous ovarian cancer.

PMID- 23542580
TI  - HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic
      dysfunction through AMP-activated protein kinase activation in a mouse model of
      metabolic syndrome.
AB  - AIMS: The metabolic syndrome (MS) leads to myocardial fibrosis (MF) and diastolic
      dysfunction. Statins have proven beneficial effects in MS, but their impact on
      cardiac remodelling is uncertain. We examined the effects and mechanisms of
      chronic statin treatment on cardiac remodelling, e.g. fibrosis and diastolic
      properties. METHODS AND RESULTS: We used a mouse model deficient in leptin and
      the LDL-receptor (DKO) that reproduces this MS phenotype. DKO mice (12 weeks)
      were treated with rosuvastatin (R) for 6 months vs. placebo. Morphometric and
      echocardiographic measurements showed that R reduced cardiac mass and increased
      left-ventricular end-diastolic diameter despite unchanged cardiomyocyte
      dimensions. Similarly, R had no effect on the hypertrophic response to
      neurohormones in isolated cardiomyocytes. Conversely, R reversed the age
      dependent development of MF as well as mRNA expression of TGF-beta1 and several
      pro-fibrotic markers (procollagen type I, its carboxy-terminal proteinase, Lysyl
      oxidase). R similarly inhibited the pro-fibrotic effects of TGF-beta1 on
      procollagen type I, alpha Smooth Muscle Actin expression and migratory properties
      of cardiac fibroblasts in vitro. In parallel, R increased the activation of AMP
      activated protein kinase (AMPK), a known inhibitor of fibrosis, in vivo and in
      vitro, and the anti-fibrotic effects of R were abrogated in fibroblasts
      transfected with AMPKalpha1/alpha2 siRNA. The reversal of MF by R in DKO mice was
      accompanied with improved diastolic properties assessed by P-V loop analysis
      (slope of EDPVR, dP/dt min and cardiac output). CONCLUSION: In this model of MS,
      statin treatment reverses myocardial remodelling and improves ventricular
      relaxation through AMPK-mediated anti-fibrotic effects.

PMID- 23542581
TI  - Functional suppression of Kcnq1 leads to early sodium channel remodelling and
      cardiac conduction system dysmorphogenesis.
AB  - AIMS: Ion channel remodelling and ventricular conduction system (VCS) alterations
      play relevant roles in the generation of cardiac arrhythmias, but the interaction
      between ion channel remodelling and cardiac conduction system dysfunctions in an
      arrhythmogenic context remain unexplored. METHODS AND RESULTS: We have used a
      transgenic mouse line previously characterized as an animal model of Long QT
      Syndrome (LQTS) to analyse ion channel remodelling and VCS configuration. Reverse
      transcriptase-PCR and immunohistochemistry analysis showed early cardiac sodium
      channel upregulation at embryonic stages prior to the onset of Kv potassium
      channel remodelling, and cardiac hypertrophy at foetal stages. In line with these
      findings, patch-clamp assays demonstrated changes in sodium current density and a
      slowing of recovery from inactivation. Functional analysis by optical mapping
      revealed an immature ventricular activation pattern as well as an increase in the
      total left ventricle activation time in foetal transgenic hearts. Morphological
      analysis of LQTS transgenic mice in a Cx40(GFP/+)background demonstrated VCS
      dysmorphogenesis during heart development. CONCLUSIONS: Our data demonstrate
      early sodium channel remodelling secondary to IKs blockage in a mouse model of
      LQTS leading to morphological and functional anomalies in the developing VCS and
      cardiac hypertrophy. These results provide new insights into the mechanisms
      underlying foetal and neonatal cardiac electrophysiological disorders, which
      might help understand how molecular, functional, and morphological alterations
      are linked to clinical pathologies such as cardiac congenital anomalies,
      arrhythmias, and perinatal sudden death.

PMID- 23542582
TI  - Structure-guided engineering of Anticalins with improved binding behavior and
      biochemical characteristics for application in radio-immuno imaging and/or
      therapy.
AB  - Modern strategies in radio-immuno therapy and in vivo imaging require robust,
      small, and specific ligand-binding proteins. In this context we have previously
      developed artificial lipocalins, so-called Anticalins, with high binding activity
      toward rare-earth metal-chelate complexes using combinatorial protein design.
      Here we describe further improvement of the Anticalin C26 via in vitro affinity
      maturation to yield CL31, which has a fourfold slower dissociation half-life
      above 2h. Also, we present the crystallographic analyses of both the initial and
      the improved Anticalin, providing insight into the molecular mechanism of
      chelated metal binding and the role of amino acid substitutions during the step
      wise affinity maturation. Notably, one of the four structurally variable loops
      that form the ligand pocket in the lipocalin scaffold undergoes a significant
      conformational change from C26 to CL31, acting as a lid that closes over the
      accommodated metal-chelate ligand. A systematic mutational study indicated that
      further improvement of ligand affinity is difficult to achieve while providing
      clues on the contribution of relevant side chains in the engineered binding
      pocket. Unexpectedly, some of the amino acid replacements led to strong increases
      - more then 10-fold - in the yield of soluble protein from periplasmic secretion
      in Escherichia coli. 

PMID- 23542583
TI  - The molecular structure within dislocations in Cannabis sativa fibres studied by
      polarised Raman microspectroscopy.
AB  - Polarised Raman micrsospectroscopy was employed to study the molecular structure
      within dislocations (slip planes) in the cell walls of Hemp fibre cells (Cannabis
      sativa (L.)). It was found that the cellulose microfibrils within dislocations
      have a different orientation than in the surrounding cell wall, and that the
      cellulose in the transition zones between a large dislocation and the surrounding
      wall may have yet another orientation. Furthermore, cellulose orientation seemed
      to be less uniform within dislocations than in the surrounding cell wall.

PMID- 23542584
TI  - Quantitative chemical evaluation of dilute GaNAs using ADF STEM: avoiding surface
      strain induced artifacts.
AB  - The high angle annular dark field intensity (HAADF) in scanning transmission
      electron microscopy (STEM) can be used for a quantitative evaluation of the
      chemical composition in dilute GaNAs quantum wells by comparison with simulated
      intensities. As the scattered intensity is highly sensitive to surface strain
      fields originating from the quantum wells embedded in GaAs, the HAADF intensity
      is difficult to evaluate in a quantitative way as long as strain contrast cannot
      be distinguished from chemical contrast. We present a method to achieve full 2D
      HAADF STEM compositional mapping of GaNAs/GaAs quantum well systems by making use
      of information from two different camera lengths.

PMID- 23542585
TI  - A mediating role of the auditory dorsal pathway in selective adaptation to
      speech: a state-dependent transcranial magnetic stimulation study.
AB  - In addition to sensory processing, recent neurobiological models of speech
      perception postulate the existence of a left auditory dorsal processing stream,
      linking auditory speech representations in the auditory cortex with articulatory
      representations in the motor system, through sensorimotor interaction interfaced
      in the supramarginal gyrus and/or the posterior part of the superior temporal
      gyrus. The present state-dependent transcranial magnetic stimulation study is
      aimed at determining whether speech recognition is indeed mediated by the
      auditory dorsal pathway, by examining the causal contribution of the left ventral
      premotor cortex, supramarginal gyrus and posterior part of the superior temporal
      gyrus during an auditory syllable identification/categorization task. To this
      aim, participants listened to a sequence of /ba/ syllables before undergoing a
      two forced-choice auditory syllable decision task on ambiguous syllables (ranging
      in the categorical boundary between /ba/ and /da/). Consistent with previous
      studies on selective adaptation to speech, following adaptation to /ba/,
      participants responses were biased towards /da/. In contrast, in a control
      condition without prior auditory adaptation no such bias was observed. Crucially,
      compared to the results observed without stimulation, single-pulse transcranial
      magnetic stimulation delivered at the onset of each target stimulus interacted
      with the initial state of each of the stimulated brain area by enhancing the
      adaptation effect. These results demonstrate that the auditory dorsal pathway
      contribute to auditory speech adaptation.

PMID- 23542586
TI  - Mesenchymal bone marrow stem cells within polyglycolic acid tube observed in vivo
      after six weeks enhance facial nerve regeneration.
AB  - Autografting is the gold-standard method for facial nerve repair with tissue
      loss. Its association with high-quality scaffolds and cell implants has disclosed
      distinct experimental outcomes. The aim of this study was to evaluate the
      functional and histological effects of bone marrow stem cells (BMSC) combined
      with polyglycolic acid tube (PGAt) in autografted rat facial nerves. After
      neurotmesis of the mandibular branch of the rat facial nerve, surgical repair
      consisted of nerve autografting (groups A-E) contained in pGAT (groups B-E),
      filled with basement membrane matrix (groups C-E) with undifferentiated BMSC
      (group D) or Schwann-like cells that had differentiated from BMSC (group E). Axon
      morphometrics and an objective compound muscle action potentials (CMAP) analysis
      were conducted. Immunofluorescence assays were carried out with Schwann cell
      marker S100 and anti-beta-galactosidase to label exogenous cells. Six weeks after
      surgery, animals from either cell-containing group had mean CMAP amplitudes
      significantly higher than control groups. Differently from other groups, facial
      nerves with Schwann-like cell implants had mean axonal densities within reference
      values. This same group had the highest mean axonal diameter in distal segments.
      We observed expression of the reporter gene lacZ in nerve cells in the graft and
      distally from it in groups D and E. Group-E cells had lacZ coexpressed with S100.
      In conclusion, regeneration of the facial nerve was improved by BMSC within PGAt
      in rats, yet Schwann-like cells were associated with superior effects.
      Accordingly, groups D and E had BMSC integrated in neural tissue with maintenance
      of former cell phenotype for six weeks.

PMID- 23542587
TI  - Isolation and culture of individual myofibers and their satellite cells from
      adult skeletal muscle.
AB  - Muscle regeneration in the adult is performed by resident stem cells called
      satellite cells. Satellite cells are defined by their position between the basal
      lamina and the sarcolemma of each myofiber. Current knowledge of their behavior
      heavily relies on the use of the single myofiber isolation protocol. In 1985,
      Bischoff described a protocol to isolate single live fibers from the Flexor
      Digitorum Brevis (FDB) of adult rats with the goal to create an in vitro system
      in which the physical association between the myofiber and its stem cells is
      preserved (1). In 1995, Rosenblattmodified the Bischoff protocol such that
      myofibers are singly picked and handled separately after collagenase digestion
      instead of being isolated by gravity sedimentation (2, 3). The Rosenblatt or
      Bischoff protocol has since been adapted to different muscles, age or conditions
      (3-6). The single myofiber isolation technique is an indispensable tool due its
      unique advantages. First, in the single myofiber protocol, satellite cells are
      maintained beneath the basal lamina. This is a unique feature of the protocol as
      other techniques such as Fluorescence Activated Cell Sorting require chemical and
      mechanical tissue dissociation (7). Although the myofiber culture system cannot
      substitute for in vivo studies, it does offer an excellent platform to address
      relevant biological properties of muscle stem cells. Single myofibers can be
      cultured in standard plating conditions or in floating conditions. Satellite
      cells on floating myofibers are subjected to virtually no other influence than
      the myofiber environment. Substrate stiffness and coating have been shown to
      influence satellite cells' ability to regenerate muscles (8, 9) so being able to
      control each of these factors independently allows discrimination between niche
      dependent and -independent responses. Different concentrations of serum have also
      been shown to have an effect on the transition from quiescence to activation. To
      preserve the quiescence state of its associated satellite cells, fibers should be
      kept in low serum medium (1-3). This is particularly useful when studying genes
      involved in the quiescence state. In serum rich medium, satellite cells quickly
      activate, proliferate, migrate and differentiate, thus mimicking the in vivo
      regenerative process (1-3). The system can be used to perform a variety of assays
      such as the testing of chemical inhibitors; ectopic expression of genes by virus
      delivery; oligonucleotide based gene knock-down or live imaging. This video
      article describes the protocol currently used in our laboratory to isolate single
      myofibers from the Extensor Digitorum Longus (EDL) muscle of adult mice (6-8
      weeks old).

PMID- 23542588
TI  - Glucose-TOR signalling reprograms the transcriptome and activates meristems.
AB  - Meristems encompass stem/progenitor cells that sustain postembryonic growth of
      all plant organs. How meristems are activated and sustained by nutrient
      signalling remains enigmatic in photosynthetic plants. Combining chemical
      manipulations and chemical genetics at the photoautotrophic transition
      checkpoint, we reveal that shoot photosynthesis-derived glucose drives target-of
      rapamycin (TOR) signalling relays through glycolysis and mitochondrial
      bioenergetics to control root meristem activation, which is decoupled from direct
      glucose sensing, growth-hormone signalling and stem-cell maintenance.
      Surprisingly, glucose-TOR signalling dictates transcriptional reprogramming of
      remarkable gene sets involved in central and secondary metabolism, cell cycle,
      transcription, signalling, transport and protein folding. Systems, cellular and
      genetic analyses uncover TOR phosphorylation of E2Fa transcription factor for an
      unconventional activation of S-phase genes, and glucose-signalling defects in
      e2fa root meristems. Our findings establish pivotal roles of glucose-TOR
      signalling in unprecedented transcriptional networks wiring central metabolism
      and biosynthesis for energy and biomass production, and integrating localized
      stem/progenitor-cell proliferation through inter-organ nutrient coordination to
      control developmental transition and growth.

PMID- 23542589
TI  - Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1.
AB  - Our innate immune system distinguishes microbes from self by detecting conserved
      pathogen-associated molecular patterns. However, these are produced by all
      microbes, regardless of their pathogenic potential. To distinguish virulent
      microbes from those with lower disease-causing potential the innate immune system
      detects conserved pathogen-induced processes, such as the presence of microbial
      products in the host cytosol, by mechanisms that are not fully resolved. Here we
      show that NOD1 senses cytosolic microbial products by monitoring the activation
      state of small Rho GTPases. Activation of RAC1 and CDC42 by bacterial delivery or
      ectopic expression of SopE, a virulence factor of the enteric pathogen
      Salmonella, triggered the NOD1 signalling pathway, with consequent RIP2 (also
      known as RIPK2)-mediated induction of NF-kappaB-dependent inflammatory responses.
      Similarly, activation of the NOD1 signalling pathway by peptidoglycan required
      RAC1 activity. Furthermore, constitutively active forms of RAC1, CDC42 and RHOA
      activated the NOD1 signalling pathway. Our data identify the activation of small
      Rho GTPases as a pathogen-induced process sensed through the NOD1 signalling
      pathway.

PMID- 23542590
TI  - A pathogenic picornavirus acquires an envelope by hijacking cellular membranes.
AB  - Animal viruses are broadly categorized structurally by the presence or absence of
      an envelope composed of a lipid-bilayer membrane, attributes that profoundly
      affect stability, transmission and immune recognition. Among those lacking an
      envelope, the Picornaviridae are a large and diverse family of positive-strand
      RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that
      remains a common cause of enterically transmitted hepatitis. HAV infects in a
      stealth-like manner and replicates efficiently in the liver. Virus-specific
      antibodies appear only after 3-4 weeks of infection, and typically herald its
      resolution. Although unexplained mechanistically, both anti-HAV antibody and
      inactivated whole-virus vaccines prevent disease when administered as late as 2
      weeks after exposure, when virus replication is well established in the liver.
      Here we show that HAV released from cells is cloaked in host-derived membranes,
      thereby protecting the virion from antibody-mediated neutralization. These
      enveloped viruses ('eHAV') resemble exosomes, small vesicles that are
      increasingly recognized to be important in intercellular communications. They are
      fully infectious, sensitive to extraction with chloroform, and circulate in the
      blood of infected humans. Their biogenesis is dependent on host proteins
      associated with endosomal-sorting complexes required for transport (ESCRT),
      namely VPS4B and ALIX. Whereas the hijacking of membranes by HAV facilitates
      escape from neutralizing antibodies and probably promotes virus spread within the
      liver, anti-capsid antibodies restrict replication after infection with eHAV,
      suggesting a possible explanation for prophylaxis after exposure. Membrane
      hijacking by HAV blurs the classic distinction between 'enveloped' and 'non
      enveloped' viruses and has broad implications for mechanisms of viral egress from
      infected cells as well as host immune responses.

PMID- 23542592
TI  - Arresting transcription and sentencing the cell: the consequences of blocked
      transcription.
AB  - Bulky DNA adducts induced by agents like ultraviolet light, cisplatin and
      oxidative metabolism pose a block to elongation by RNA polymerase II (RNAPII).
      The arrested RNAPII can initiate the repair of transcription-blocking DNA lesions
      by transcription-coupled nucleotide excision repair (TC-NER) to permit efficient
      recovery of mRNA synthesis while widespread sustained transcription blocks lead
      to apoptosis. Therefore, RNAPII serves as a processive DNA damage sensor that
      identifies transcription-blocking DNA lesions. Cockayne syndrome (CS) is an
      autosomal recessive disorder characterized by a complex phenotype that includes
      clinical photosensitivity, progressive neurological degeneration and premature
      aging. CS is associated with defects in TC-NER and the recovery of mRNA
      synthesis, making CS cells exquisitely sensitive to a variety of DNA damaging
      agents. These defects in the coupling of repair and transcription appear to
      underlie some of the complex clinical features of CS. Recent insight into the
      consequences of blocked transcription and their relationship to CS will be
      discussed.

PMID- 23542591
TI  - Crystal structure of a eukaryotic phosphate transporter.
AB  - Phosphate is crucial for structural and metabolic needs, including nucleotide and
      lipid synthesis, signalling and chemical energy storage. Proton-coupled
      transporters of the major facilitator superfamily (MFS) are essential for
      phosphate uptake in plants and fungi, and also have a function in sensing
      external phosphate levels as transceptors. Here we report the 2.9 A structure of
      a fungal (Piriformospora indica) high-affinity phosphate transporter, PiPT, in an
      inward-facing occluded state, with bound phosphate visible in the membrane-buried
      binding site. The structure indicates both proton and phosphate exit pathways and
      suggests a modified asymmetrical 'rocker-switch' mechanism of phosphate
      transport. PiPT is related to several human transporter families, most notably
      the organic cation and anion transporters of the solute carrier family (SLC22),
      which are implicated in cancer-drug resistance. We modelled representative cation
      and anion SLC22 transporters based on the PiPT structure to surmise the
      structural basis for substrate binding and charge selectivity in this important
      family. The PiPT structure demonstrates and expands on principles of substrate
      transport by the MFS transporters and illuminates principles of phosphate uptake
      in particular.

PMID- 23542593
TI  - Radiological incidence of parastomal herniation in cancer patients with permanent
      colostomy: what is the ideal size of the surgical aperture?
AB  - BACKGROUND: Parastomal herniation frequently complicates stoma formation.
      Aperture size has been shown to be an independent predictor of hernia development
      but there is a paucity of data regarding the ideal stoma diameter. The aim of
      this study was to establish the radiological incidence of herniation in patients
      with a permanent colostomy and correlate it with the size of the abdominal wall
      defect in order to identify an aperture diameter associated with a reduced
      herniation risk. METHODS: All patients who underwent permanent colostomy
      formation for colorectal cancer over a five-year period in a single institution
      were recruited to the study. Patient demographics, operative details and stoma
      related symptoms were recorded. Post-operative CT scans were reviewed for
      evidence of parastomal herniation. The diameter of the abdominal wall defect was
      measured radiologically. RESULTS: 43 patients (mean age 69 years) were included
      in the analysis. Radiologically, 25/43 (58%) had evidence of a parastomal hernia.
      The median aperture diameter was 35 mm (range 25-58 mm) in patients with a
      parastomal hernia and 22 mm (range 10-36 mm) in patients without herniation (p <
      0.0001). There were no cases of herniation with an abdominal wall defect size <25
      mm. The median follow up was 26.0 months (range 6-55) in patients with herniation
      as opposed to 16.0 months (range 7-36) in patients without herniation (p = 0.11).
      CONCLUSION: The majority of patients with a permanent colostomy develop a
      parastomal hernia within the first two post-operative years. Parastomal
      herniation appears unlikely to develop with an abdominal wall defect diameter
      <=25 mm provided this does not enlarge with time. Surgical techniques that
      utilise stapling devices to form a 'custom-made' and rigid trephine might reduce
      the herniation risk.

PMID- 23542594
TI  - The comparison of neuroprotective effects of intrathecal dexmedetomidine and
      metilprednisolone in spinal cord injury.
AB  - BACKGROUND: The purpose of this study is the investigation of the effects of
      intrathecally injected dexmedetomidine and methylprednisolone and their dominancy
      over one another in rats with generated Spinal Cord Injury (SCI). METHODS: 40,
      female, adult Wistar Albino rats weighing 220-260 g were included in the study.
      The rats were fixed with Intrathecal catheter (IT) and divided into four groups.
      All subjects were applied T7-10 laminectomy after catheter. Group S (n:10) was
      injected with IT 10 MUL isotonic saline; Group C (n:10) with IT 10 MUL isotonic
      saline after SCI; Group D (n:10) with IT one doze 10 MUL of dexmedetomidine after
      SCI; Group M (n:10) IT one dose 10 MUL of methylprednisolone. The subjects were
      sacrificed 72 h after this operation. The damaged area was removed biochemically
      and histopathologically examined. RESULTS: Antioxidant and inflammatory
      parameters searched for in all damages tissue were statistically different in all
      groups from group S. They were different in group M and group D than group C (p <
      0.001). After the comparison of group D and group M, PON and IL6 values were
      higher in group D (p = 0.003, p = 0.035) while the other two biochemical
      parameters were similar in both groups (Table 1). After histopathologic trials,
      edemas, bleeding and necrosis were found less in group S while at the most in
      group C (p < 0.001). In group M and group D, however, they were higher than group
      S and lower than group C (p < 0.001). After the comparison of group D and group
      M, while there was no difference in terms of edema necrosis, the amount of
      bleeding was lower in group D (p < 0.001) (Table 2). CONCLUSIONS: It has been
      discovered that intrathecal use of dexmedetomidine caused neuroprotective effects
      similar to methylprednisolone.

PMID- 23542595
TI  - Synthesis and evaluation of the antioxidative potential of minoxidil-polyamine
      conjugates.
AB  - A series of conjugates (MNX-CO-PA) of minoxidil (MNX) with the polyamines (PAs)
      putrescine (PUT), spermidine (SPD) and spermine (SPM) as well as dopamine were
      produced through activation of MNX with N,N'-carbonyldiimidazole, followed by
      reaction with dopamine or selectively protected PAs and acid-mediated
      deprotection. These conjugates together with conjugates of the general type MNX
      PA or PA-MNX-PA, readily produced using literature protocols, were tested as
      antioxidants. The most potent inhibitors of lipid peroxidation were the
      conjugates MNX-SPM (2, 94%), SPM-MNX-SPM (4, 94%) and MNX-N(4)-SPD (7, 91%) and
      MNX (91%). The most powerful lipoxygenase (LOX) inhibitors were MNX (IC50 = 20
      MUM) and the conjugates MNX-N(8)-SPD (9, IC50 = 22.1 MUM), MNX-CO-dopamine (11,
      IC50 = 28 MUM) and MNX-N(1)-SPD (8, IC50 = 30 MUM). The most interesting
      conjugates 2, MNX-CO-PUT (5), 8 and 11 as well as MNX were generally found to
      exhibit weaker (22-36.5%) or no (conjugate 8) anti-inflammatory activity than
      indomethacin (47%) with the exception of MNX which showed almost equal potency
      (49%) to indomethacin. The cytocompatibility of conjugates and MNX at the highest
      concentration of 100 MUM showed a survival percentage of 87-107%, with the
      exception of conjugates with SPM (compound 2) and MNX-CO-SPM (6), which showed
      considerable cytotoxicity (survival percentage 8-14%). Molecular docking studies
      were carried on conjugate 9 and the parent compound MNX and were found to be in
      accordance with our experimental biological results.

PMID- 23542596
TI  - MicroRNA-29 family, a crucial therapeutic target for fibrosis diseases.
AB  - MicroRNAs (miRNAs) are a class of approximately 20-nucleotides single-stranded
      endogenous RNAs that regulate gene expression at the post-transcriptional level.
      miRNAs have recently been known to regulate cell proliferation, differentiation,
      and apoptosis. Fibrosis is the leading cause of organ dysfunction in diseases and
      results from an imbalance in the turnover of extracellular matrix components.
      Accumulating studies have demonstrated that miR-29 family participates in the
      development of liver fibrosis, renal fibrosis, pulmonary fibrosis, cardiac
      fibrosis. In this review, we are discussing the comprehensive role of miR-29
      family in moderating profibrotic effect and its potential as therapeutic approach
      to fibrosis diseases.

PMID- 23542599
TI  - The foliar uptake and downward translocation of trichloroethylene and 1,2,3
      trichlorobenzene in air-plant-water systems.
AB  - The foliar uptake and downward translocation of trichloroethylene (TCE) and 1,2,3
      trichlorobenzene (TCB) in wheat, corn, and tomato seedlings were investigated
      following 2-48-h exposure of the plant shoots to vapor-contaminated air. The
      results showed that both TCE and TCB could be rapidly transported from air to
      plant rhizosphere solution through the foliar uptake and downward transport; the
      TCE and TCB concentrations in rhizosphere solutions increased with exposure time
      and external contaminant concentration. Among the three plant species studied,
      the TCE and TCB downward transport followed the order of wheat>tomato>corn. The
      transport efficiency of TCE by the three plants was far greater than that of TCB.
      With a 24-h uptake time, the amounts of TCE transported into the rhizosphere
      solution by wheat, tomato, and corn seedlings were 2.39 +/- 0.42, 1.50 +/- 0.22
      and 1.45 +/- 0.08 MUg TCE per gram of fresh weight biomass, respectively, when
      the initial external TCE concentration was set at 12 mg l(-1). In a 48-h uptake
      experiment with corn seedlings, the TCE concentration in the rhizosphere
      solutions was lower in the TCE-TCB mixture system than in the single TCE system,
      whereas there was no significant difference in TCB concentration between the
      single TCB and TCE-TCB mixture systems at 48 h. The downward transport processes
      of TCE were inhibited, while those of TCB were enhanced in the mixed contaminant
      system within a 48-h uptake time.

PMID- 23542600
TI  - Oxidative stress response of two fluoroquinolones with catalase and erythrocytes:
      a combined molecular and cellular study.
AB  - Ciprofloxacin (CPFX) and enrofloxacin (ENFX), two representatives of
      fluoroquinolones (FQs), pose potential threats to health for their wide exposures
      in environment. The aim of the study is to characterize the harmful effects of
      oxidative stress induced by CPFX and ENFX from the structure and function of
      catalase (CAT), a vital enzyme involved in protection against oxidative damage.
      The cellular tests firstly confirmed an enhanced oxidative stress in FQs treated
      erythrocytes from the depletion of GSH contents and decrease of CAT activity.
      Besides, CPFX posed more of an oxidative threat than ENFX. During the
      spectroscopic and computational investigations, both FQs could bind into its
      central cavity with only one binding site and interact with Arg 65, Arg 362 and
      His 363 mainly through electrostatic forces. Furthermore, the binding of two FQs
      not only caused the conformational and micro-environmental changes of CAT, but
      also inhibited its molecular activity, consistent with the cellular activity
      measurements. All these results suggested that the structural and functional
      changes of CAT were closely associated with increased risk of oxidative stress
      induced by both FQs. The established methods in this work can help to
      comprehensively understanding the oxidative stress-induced cellular damage of
      other pollutants via antioxidant effects.

PMID- 23542601
TI  - Characterization of size, strength and structure of aluminum-polymer dual
      coagulant flocs under different pH and hydraulic conditions.
AB  - The objectives of this study are to investigate the impact of papermaking sludge
      product (LA) on coagulation performance and floc properties under different
      solution pH and hydraulic conditions. LA was synthetized by grafting acrylamide
      onto the lignin that contained in papermaking sludge. Characterization of LA,
      such as FTIR, SEM, zeta potential and molecular weight, showed that target
      product was obtained successfully. LA was used in combination with aluminum
      sulfate or polyaluminum chloride, namely Al-LA (Al was dosed firstly) and LA-Al
      (LA was dosed firstly), in humic acid water treatment. Floc properties and
      coagulation behaviors of aluminum salts and the dual-coagulants were
      comparatively evaluated. Results showed that DOC removal was improved by LA at pH
      4 ~ 9 and the removal variations caused by different pH were decreased. Flocs
      formed at pH 5 and pH 8 gave quite large floc size. Floc recoverability declined
      as initial pH increased. Floc size, growth rate and recoverability were in the
      order of Al-LA>LA-Al>Al. Furthermore, flocs formed at pH 7 showed the weakest
      resistance to increasing shear force. Fractal dimension was rather high at pH 7
      and 8 and it was in the following order: Al>LA-Al>Al-LA.

PMID- 23542602
TI  - Grass carp (Ctenopharyngodon idella) TRAF6 and TAK1: molecular cloning and
      expression analysis after Ichthyophthirius multifiliis infection.
AB  - Ichthyophthirius multifiliis, a pathogenic ciliate parasite, infects almost all
      freshwater fish species and causes significant economic losses. Tumor necrosis
      factor receptor-associated factor 6 (TRAF6) and transforming growth factor-beta
      activated kinase 1 (TAK1) are two important signaling molecules involved in toll
      like receptor (TLR) signal transduction. To date, the roles of TRAF6 and TAK1 in
      host defense against fish parasites are still poorly understood. In the present
      study, TRAF6 (CiTRAF6) and TAK1 (CiTAK1) were identified from grass carp
      (Ctenopharyngodon idella). The full-length cDNA sequence of CiTRAF6 (2250 bp)
      includes an open reading frame (ORF) of 1629 bp, which shows a high similarity to
      that of Cyprinus carpio TRAF6 and encodes a putative protein of 542 amino acids
      containing one RING domain, two zinc fingers, one coiled-coil region, and one
      MATH domain. The full-length CiTAK1 cDNA sequence is 2768 bp and includes an ORF
      of 1626 bp that encodes a putative protein of 541 amino acids containing a
      conserved serine/threonine protein kinase catalytic domain and a coiled-coil
      region. Phylogenetic analysis showed that CiTRAF6 and CiTAK1 were clustered with
      TRAF6 and TAK1 of other teleosts, respectively. CiTRAF6 and CiTAK1 were both
      constitutively expressed in all examined tissues but with varied expression
      levels. The highest expressions of CiTRAF6 and CiTAK1 were in the head kidney and
      spleen, respectively. The expression profiles of CiTRAF6 and CiTAK1 were detected
      in grass carp after I. multifiliis infection. Expressions of both genes were
      significantly up-regulated in the skin, gill, head kidney, and spleen at most
      time points after infection, indicating that CiTRAF6 and CiTAK1 may play
      essential roles in grass carp defense against I. multifiliis.

PMID- 23542603
TI  - Cloning and preliminary functional studies of the JAM-A gene in grass carp
      (Ctenopharyngodon idellus).
AB  - Grass carp (Ctenopharyngodon idellus) is a very important aquaculture species in
      China and other South-East Asian countries; however, disease outbreaks in this
      species are frequent, resulting in huge economic losses. Grass carp hemorrhage
      caused by grass carp reovirus (GCRV) is one of the most serious diseases.
      Junction adhesion molecule A (JAM-A) is the mammalian receptor for reovirus, and
      has been well studied. However, the JAM-A gene in grass carp has not been studied
      so far. In this study, we cloned and elucidated the structure of the JAM-A gene
      in grass carp (GcJAM-A) and then studied its functions during grass carp
      hemorrhage. GcJAM-A is composed of 10 exons and 9 introns, and its full-length
      cDNA is 1833 bp long, with an 888 bp open reading frame (ORF) that encodes a 295
      amino acid protein. The GcJAM-A protein is predicted to contain a typical
      transmembrane domain. Maternal expression pattern of GcJAM-A is observed during
      early embryogenesis, while zygote expression occurs at 8 h after hatching. GcJAM
      A is expressed strongly in the gill, liver, intestine and kidney, while it is
      expressed poorly in the blood, brain, spleen and head kidney. Moreover, lower
      expression is observed in the gill, liver, intestine, brain, spleen and kidney of
      30-month-old individuals, compared with 6-month-old. In a GcJAM-A-knockdown cell
      line (CIK) infected with GCRV, the expression of genes involved in the interferon
      and apoptosis pathways was significantly inhibited. These results suggest that
      GcJAM-A could be a receptor for GCRV. We have therefore managed to characterize
      the GcJAM-A gene and provide evidence for its role as a receptor for GCRV.

PMID- 23542604
TI  - Heat shock protein profiles on the protein and gene expression levels in olive
      flounder kidney infected with Streptococcus parauberis.
AB  - Heat shock proteins (HSPs) have been observed in cells exposed to a variety of
      stresses, including infectious pathogens. This study used a label-free,
      quantitative proteomic approach and transcriptional gene expression analysis to
      investigate infection-related HSP proteins and their encoding genes in whole
      kidneys from olive flounder (Paralichthys olivaceus). During Streptococcus
      parauberis infection in the flounder, the genes encoding Hsp10, Hsp40A4, Hsp40B6,
      Hsp40B11, Hsp60, Hsp70, glucose regulated protein 78 (Grp78), Hsp90alpha,
      Hsp90beta and Grp94 were induced, and the protein levels of Hsp60, Hsp70,
      Hsp90alpha, Hsp90beta and Grp94 were differentially regulated over time.
      Subsequent results also revealed that Hsp60, Hsp70, Hsp90alpha, Hsp90beta and
      Grp94 appear to be the dominant and critical HSPs in olive flounder during
      bacterial infection. This is the first estimation of the differential involvement
      of HSPs in the immune response of olive flounder exposed to bacterial infection.

PMID- 23542605
TI  - Effects of vitamin E on expressions of eight microRNAs in the liver of Nile
      tilapia (Oreochromis niloticus).
AB  - Currently, microRNAs (miRNAs) are known to regulate cellular processes such as
      apoptosis, differentiation, cell cycle, and immune functions, and their
      expression can be altered by distinct stress conditions, such as oxidative
      stress. In immune systems of fish, vitamin E (VE) has a defined role as an
      antioxidant. In order to understand the molecular mechanism of vitamin E
      defending from oxidative stress, three groups of juvenile Nile tilapia
      (Oreochromis niloticus) (initial weight 3.25 +/- 0.02 g) were fed to satiation
      with 3 semi-purified diets containing VE (DL-alpha-tocopherol acetate) of 0, 50,
      and 2500 mg/kg supplementation, respectively, with the expressions of eight
      miRNAs (miR-21, miR-223, miR-146a, miR-125b, miR-181a, miR-16, miR-155 and miR
      122) in the liver of tilapia subsequently detected after 8-week growth
      experiment. Results showed that VE-deficient (0 mg/kg supplementation) decreased
      the activity of superoxide dismutase (SOD), and decreased the expressions of miR
      223, miR-146a, miR-16 and miR-122, while excessive supplementation of VE (2500
      mg/kg) decreased SOD activity and increased the expressions of all the eight
      miRNAs. The targets of the eight miRNAs were further predicated with
      bioinformatic approach and the possible regulating mechanisms of VE via miRNAs
      were analyzed. The present study confirmed that the differences in dietary VE
      affected expression of hepatic miRNAs which may partly demonstrate the molecular
      mechanism of VE, and the new idea of introducing miRNAs into research will
      provide the basic data for researches of molecular nutrition.

PMID- 23542606
TI  - IRF-1 acts as a positive regulator in the transcription of grass carp
      (Ctenopharyngodon idella) IFN gene.
AB  - Interferon regulatory factors (IRFs) are well-known to be crucial for modulating
      the innate immune responses to viral infections. In the present study, the IRF-1
      gene of grass carp (Ctenopharyngodon idella) (termed CiIRF-1) was cloned and
      characterized. The complete genomic sequence of CiIRF-1 was 3150 bp in length and
      comprised 9 exons and 8 introns. The CiIRF-1 promoter sequence was 558 bp in
      length. The largest open reading frame (ORF) of the full CiIRF-1 cDNA sequence
      was 870 bp, and encoded a polypeptide of 289 amino acids. The putative CiIRF-1
      was characterized by a conserved N-terminal DBD (113 aa), and included a
      signature of five conserved tryptophan residues. Phylogenetic relationship
      analysis revealed that CiIRF-1 was highly homologous to the counterparts of other
      teleosts and mammalians. CiIRF-1 was expressed at a low constitutive level but
      was significantly up-regulated following stimulation with either Poly I:C or
      recombinant grass carp (C. idella) IFN (rCiIFN) in all 6 tested tissues,
      especially in spleen and gill. The recombinant CiIRF-1 was expressed in BL21
      Escherichia coli, and the expressed protein was purified by affinity
      chromatography with the Ni-NTA His-Bind Resin. Three different fragments of
      promoter sequences from grass carp type I IFN (CiIFN) gene (GU139255) were
      amplified. These fragments included the proximal region (CiIFNP2), the distal
      region (CiIFNP6), and the full length of CiIFN promoter sequences (CiIFNP7). Gel
      mobility shift assays were employed to analyze the interaction between CiIRF-1
      and CiIFN promoter sequences. The results revealed that CiIRF-1 could bind to
      CiIFN promoter with high affinity in vitro. Subsequently, the recombinant plasmid
      of pGL3-CiIFNPs and pcDNA3.1-CiIRF-1 were constructed and transiently co
      transfected into C. idella kidney (CIK) cells. The impact of CiIRF-1 on CiIFN
      promoter sequences were measured by luciferase assays. These results demonstrated
      that CiIRF-1 acts as a positive regulator in the transcription of grass carp IFN
      gene.

PMID- 23542607
TI  - Quantification of cabazitaxel, its metabolite docetaxel and the determination of
      the demethylated metabolites RPR112698 and RPR123142 as docetaxel equivalents in
      human plasma by liquid chromatography-tandem mass spectrometry.
AB  - We present a sensitive validated LC-MS/MS assay for the simultaneous
      determination of cabazitaxel and docetaxel in human plasma, with calibration
      ranges of 1.0-150 ng/mL for cabazitaxel and 0.1-15 ng/mL for docetaxel. Sample
      pretreatment consisted of liquid-liquid extraction with tert-butyl methyl ether.
      Chromatographic separation was achieved on a Zorbax Extend C18 column using a
      gradient mixture of 10mM ammonium hydroxide and methanol. Mass detection was
      carried out by turbo ion spray ionization in positive ion multiple reaction
      monitoring mode. All inter-day accuracies and precisions were within +/-15% of
      the nominal value and within +/-20% at the lower limit of quantitation.
      Demethylations of cabazitaxel yielding the metabolites RPR112698 and RPR123142
      were monitored semi-quantitatively and quantified as ng docetaxel equivalents.
      Plasma samples of a prostate cancer patient treated with cabazitaxel were
      analyzed to demonstrate the usefulness of the presented assay for clinical drug
      monitoring. In conclusion, this method can be applied to support clinical
      pharmacokinetic studies with the novel anticancer drug cabazitaxel.

PMID- 23542608
TI  - Pulmonary DWCNT exposure causes sustained local and low-level systemic
      inflammatory changes in mice.
AB  - Carbon nanotubes (CNTs) represent promising vectors to facilitate cellular drug
      delivery and to overcome biological barriers, but some types may also elicit
      persistent pulmonary inflammation based on their fibre characteristics. Here, we
      show the pulmonary response to aqueous suspensions of block copolymer dispersed,
      double-walled carbon nanotubes (DWCNT, length 1-10 MUm) in mice by
      bronchoalveolar lavage (BAL) analysis, and BAL and blood cytokine and lung
      antioxidant profiling. The intratracheally instilled dose of 50 MUg DWCNT caused
      significant pulmonary inflammation that was not resolved during a 7-day
      observation period. Light microscopy investigation of the uptake of DWCNT
      agglomerates revealed no particle ingestion for granulocytes, but only for
      macrophages. Accumulating macrophage, multinucleated macrophage and lymphocyte
      numbers in the alveolar region further indicated ineffective resolution with
      chronification of the inflammation. The local inflammatory impairment of the lung
      was accompanied by pulmonary antioxidant depletion and haematological signs of
      systemic inflammation. While the observed inflammation during its acute phase was
      dominated by neutrophils and neutrophil recruiting cytokines, the contribution of
      macrophages and lymphocytes with related cytokines became more significant after
      day 3 of exposure. This study confirms that acute pulmonary toxicity can occur on
      exposure of high doses of DWCNT agglomerates and offers further insight for
      improved nanotube design parameters to avoid potential long-term toxicity.

PMID- 23542609
TI  - A GLUE uncertainty analysis of a drying model of pharmaceutical granules.
AB  - A shift from batch processing towards continuous processing is of interest in the
      pharmaceutical industry. However, this transition requires detailed knowledge and
      process understanding of all consecutive unit operations in a continuous
      manufacturing line to design adequate control strategies. This can be facilitated
      by developing mechanistic models of the multi-phase systems in the process. Since
      modelling efforts only started recently in this field, uncertainties about the
      model predictions are generally neglected. However, model predictions have an
      inherent uncertainty (i.e. prediction uncertainty) originating from uncertainty
      in input data, model parameters, model structure, boundary conditions and
      software. In this paper, the model prediction uncertainty is evaluated for a
      model describing the continuous drying of single pharmaceutical wet granules in a
      six-segmented fluidized bed drying unit, which is part of the full continuous
      from-powder-to-tablet manufacturing line (ConsigmaTM, GEA Pharma Systems). A
      validated model describing the drying behaviour of a single pharmaceutical
      granule in two consecutive phases is used. First of all, the effect of the
      assumptions at the particle level on the prediction uncertainty is assessed.
      Secondly, the paper focuses on the influence of the most sensitive parameters in
      the model. Finally, a combined analysis (particle level plus most sensitive
      parameters) is performed and discussed. To propagate the uncertainty originating
      from the parameter uncertainty to the model output, the Generalized Likelihood
      Uncertainty Estimation (GLUE) method is used. This method enables a modeller to
      incorporate the information obtained from the experimental data in the assessment
      of the uncertain model predictions and to find a balance between model
      performance and data precision. A detailed evaluation of the obtained uncertainty
      analysis results is made with respect to the model structure, interactions
      between parameters and uncertainty boundaries. 

PMID- 23542610
TI  - Chemiluminescence and ELISA-based serum assays for diagnosing and monitoring
      celiac disease in children: a comparative study.
AB  - BACKGROUND: Anti-transglutaminase (tTG) or anti-deamidated gliadin peptides (DGP)
      serum determination is the first step in diagnosing celiac disease (CD). Our aims
      were to: compare the performance of novel chemiluminescent tool in the detection
      of tTG and DGP (Q-Flash(r), Inova) with that of the established ELISA (Q-Lite(r),
      Inova) methods; identify the more reliable index for making a sound diagnosis and
      monitoring therapy. METHODS: Using Q-Flash(r) and Q-Lite(r), IgA and IgG class
      tTG and DGP were measured in the sera of 155 CD pediatric patients and 166
      healthy age-matched controls. Forty-two of the patients had a follow-up one year
      after starting gluten free diet (GFD). RESULTS: Q-Flash(r) IgA tTG, the more
      accurate (intra-assay CV for low, intermediate and high values: 2.2%, 1.6%, and
      1.1%; inter-assay CV: 2.8%, 4%, and 3%), sensitive (96.1%) and specific (97%)
      test for diagnosing CD, was the only variable to be significantly correlated with
      CD at binary logistic regression analysis (r=0.263, p<0.0001, Exp(B)=1.0506, 95%
      CI=1.0286-1.0731). Q-Flash(r) IgA tTG or DGP screen were more accurate than Q
      Lite(r) IgA tTG in monitoring CD patients on GFD (p=0.003). CONCLUSION: Q-
      Flash(r) IgA tTG measurement is an extremely precise, sensitive and specific
      index for not only diagnosing CD, but also monitoring therapy.

PMID- 23542611
TI  - Efficacy and safety of epratuzumab in patients with moderate/severe flaring
      systemic lupus erythematosus: results from two randomized, double-blind, placebo
      controlled, multicentre studies (ALLEVIATE) and follow-up.
AB  - OBJECTIVE: To evaluate epratuzumab treatment in patients with moderately-to
      severely active SLE in two international, randomized, controlled trials
      (ALLEVIATE-1 and -2) and an open-label extension study (SL0006). METHODS: Ninety
      ALLEVIATE patients (43% BILAG A, median BILAG score 12.0) received standard of
      care plus 10 total doses of placebo (n = 37) or 360 mg/m(2) (n = 42) or 720
      mg/m(2) (n = 11) epratuzumab, administered across 12-week cycles for up to 48
      weeks, with BILAG assessments every 4 weeks. Patients were followed for >= 6
      months and their data combined for analysis. The primary endpoint was BILAG
      response at week 12 (all BILAG A scores reduced to B/C/D and B scores to C/D, no
      new A and <2 new B scores). Twenty-nine patients continued in SL0006, receiving
      12-week cycles of 360 mg/m(2) epratuzumab; this interim analysis was performed at
      median 120 weeks (range 13-184) of exposure. RESULTS: Both ALLEVIATE trials were
      discontinued prematurely because of interruption in drug supply. Exploratory
      pooled analyses found that responses at week 12 were 15/34 (44.1%) and 2/10
      (20.0%) for epratuzumab 360 and 720 mg/m(2), respectively, vs 9/30 (30.0%) for
      placebo. Total BILAG scores were lower in both epratuzumab arms vs placebo at
      week 48 and at all but two time points. The incidence of adverse events was
      similar between groups. In SL0006, median total BILAG score was 8.0 (n = 29) at
      study entry and 7.0 (n = 19) at week 100, with no additional safety signals.
      CONCLUSION: This initial efficacy and safety profile of epratuzumab supports its
      continued development for SLE treatment.

PMID- 23542612
TI  - A multicentre, randomized, placebo- and active-controlled trial comparing the
      efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with
      ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated
      with osteoarthritis.
AB  - OBJECTIVE: To assess the efficacy and safety of 12-week treatment with ketoprofen
      in ultradeformable phospholipid vesicles in patients with OA knee pain and to
      compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS;
      A multicentre, double-blind controlled study in which patients with knee OA and
      moderate pain were randomized to one of the six arms: topical ketoprofen 50 or
      100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free
      vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The
      primary outcome was change from baseline in the WOMAC pain subscale at week 12.
      RESULTS: A total of 1395 patients received treatment. Baseline mean WOMAC pain
      scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain
      score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for
      ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT
      064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was
      not statistically superior to TDT 064. All topical treatments were statistically
      superior to oral placebo and non-inferior to celecoxib. The most frequent types
      of treatment-related adverse events reported were gastrointestinal for oral
      (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen
      100 mg). CONCLUSION: IDEA-033 was not superior to ketoprofen-free vehicle, but
      both formulations were superior to oral placebo and non-inferior to celecoxib in
      reducing OA knee pain. TRIAL REGISTRATION: ClinicalTrials.gov,
      http://clinicaltrials.gov/, NCT00716547.

PMID- 23542613
TI  - Phenotype overlap in Xylella fastidiosa is controlled by the cyclic di-GMP
      phosphodiesterase Eal in response to antibiotic exposure and diffusible signal
      factor-mediated cell-cell signaling.
AB  - Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in
      resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain
      proteins are implicated in the hydrolysis of the secondary messenger bis-(3'-5')
      cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated
      by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X.
      fastidiosa, thereby controlling the expression of virulence genes and genes
      involved in insect transmission. The possible linkage of Eal to both extrinsic
      factors such as antibiotics and intrinsic factors such as quorum sensing, and
      whether both affect virulence, was thus addressed. Expression of eal was induced
      by subinhibitory concentrations of tobramycin, and an eal deletion mutant was
      more susceptible to this antibiotic than the wild-type strain and exhibited
      phenotypes similar to those of an rpfF deletion mutant blocked in DSF production,
      such as hypermotility, reduced biofilm formation, and hypervirulence to grape.
      Consistent with that, the rpfF mutant was more susceptible than the wild-type
      strain to tobramycin. Therefore, we propose that cell-cell communication and
      antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in
      X. fastidiosa, resulting in similar phenotypes. However, the effect of cell
      density is dominant compared to that of antibiotic stress, since eal is
      suppressed by RpfF, which may prevent inappropriate behavioral changes in
      response to antibiotic stress when DSF accumulates.

PMID- 23542614
TI  - Effects of Bartonella spp. on flea feeding and reproductive performance.
AB  - Numerous pathogens are transmitted from one host to another by hematophagous
      insect vectors. The interactions between a vector-borne organism and its vector
      vary in many ways, most of which are yet to be explored and identified. These
      interactions may play a role in the dynamics of the infection cycle. One way to
      evaluate these interactions is by studying the effects of the tested organism on
      the vector. In this study, we tested the effects of infection with Bartonella
      species on fitness-related variables of fleas by using Bartonella sp. strain OE 1
      1, Xenopsylla ramesis fleas, and Meriones crassus jirds as a model system.
      Feeding parameters, including blood meal size and metabolic rate during
      digestion, as well as reproductive parameters, including fecundity, fertility,
      and life span, were compared between fleas experimentally infected with
      Bartonella and uninfected fleas. In addition, the developmental time, sex ratio,
      and body size of F1 offspring fleas were compared between the two groups. Most
      tested parameters did not differ between infected and uninfected fleas. However,
      F1 males produced by Bartonella-positive females were significantly smaller than
      F1 males produced by Bartonella-negative female fleas. The findings in this study
      suggest that bartonellae are well adapted to their flea vectors, and by minimally
      affecting their fitness they have evolved to better spread themselves in the
      natural environment.

PMID- 23542615
TI  - Detection of Escherichia coli O104 in the feces of feedlot cattle by a multiplex
      PCR assay designed to target major genetic traits of the virulent hybrid strain
      responsible for the 2011 German outbreak.
AB  - A multiplex PCR was designed to detect Escherichia coli O104:H4, a hybrid
      pathotype of Shiga toxigenic and enteroaggregative E. coli, in cattle feces. A
      total of 248 fecal samples were tested, and 20.6% were positive for serogroup
      O104. The O104 isolates did not carry genes characteristic of the virulent hybrid
      strain.

PMID- 23542616
TI  - Effect of soil slope on the appearance of Mycobacterium avium subsp.
      paratuberculosis in water running off grassland soil after application of
      contaminated slurry.
AB  - The study assessed the effect of soil slope on Mycobacterium avium subsp.
      paratuberculosis transport into rainwater runoff from agricultural soil after
      application of M. avium subsp. paratuberculosis-contaminated slurry. Under field
      conditions, 24 plots of undisturbed loamy soil 1 by 2 m(2) were placed on
      platforms. Twelve plots were used for water runoff: 6 plots at a 3% slope and 6
      plots at a 15% slope. Half of the plots of each slope were treated with M. avium
      subsp. paratuberculosis-contaminated slurry, and half were not treated. Using the
      same experimental design, 12 plots were established for soil sampling on a
      monthly basis using the same spiked slurry application and soil slopes. Runoff
      following natural rainfall was collected and analyzed for M. avium subsp.
      paratuberculosis, coliforms, and turbidity. M. avium subsp. paratuberculosis was
      detected in runoff from all plots treated with contaminated slurry and one
      control plot. A higher slope (15%) increased the likelihood of M. avium subsp.
      paratuberculosis detection but did not affect the likelihood of finding
      coliforms. Daily rainfall increased the likelihood that runoff would have
      coliforms and the coliform concentration, but it decreased the M. avium subsp.
      paratuberculosis concentration in the runoff. When there was no runoff, rain was
      associated with increased M. avium subsp. paratuberculosis concentrations.
      Coliform counts in runoff were related to runoff turbidity. M. avium subsp.
      paratuberculosis presence/absence, however, was related to turbidity. Study
      duration decreased bacterial detection and concentration. These findings
      demonstrate the high likelihood that M. avium subsp. paratuberculosis in slurry
      spread on pastures will contaminate water runoff, particularly during seasons
      with high rainfall. M. avium subsp. paratuberculosis contamination of water has
      potential consequences for both animal and human health.

PMID- 23542617
TI  - Enzymatic synthesis of novel phloretin glucosides.
AB  - A UDP-glycosyltransferase from Bacillus licheniformis was exploited for the
      glycosylation of phloretin. The in vitro glycosylation reaction confirmed the
      production of five phloretin glucosides, including three novel glucosides.
      Consequently, we demonstrated the application of the same glycosyltransferase for
      the efficient whole-cell biocatalysis of phloretin in engineered Escherichia
      coli.

PMID- 23542618
TI  - Subtle differences in virus composition affect disinfection kinetics and
      mechanisms.
AB  - Viral disinfection kinetics have been studied in depth, but the molecular-level
      inactivation mechanisms are not understood. Consequently, it is difficult to
      predict the disinfection behavior of nonculturable viruses, even when related,
      culturable viruses are available. The objective of this work was to determine how
      small differences in the composition of the viral genome and proteins impact
      disinfection. To this end, we investigated the inactivation of three related
      bacteriophages (MS2, fr, and GA) by UV254, singlet oxygen ((1)O2), free chlorine
      (FC), and chlorine dioxide (ClO2). Genome damage was quantified by PCR, and
      protein damage was assessed by quantitative matrix-assisted laser desorption
      ionization (MALDI) mass spectrometry. ClO2 caused great variability in the
      inactivation kinetics between viruses and was the only treatment that did not
      induce genome damage. The inactivation kinetics were similar for all viruses when
      treated with disinfectants possessing a genome-damaging component (FC, (1)O2, and
      UV254). On the protein level, UV254 subtly damaged MS2 and fr capsid proteins,
      whereas GA's capsid remained intact. (1)O2 oxidized a methionine residue in MS2
      but did not affect the other two viruses. In contrast, FC and ClO2 rapidly
      degraded the capsid proteins of all three viruses. Protein composition alone
      could not explain the observed degradation trends; instead, molecular dynamics
      simulations indicated that degradation is dictated by the solvent-accessible
      surface area of individual amino acids. Finally, despite the similarities of the
      three viruses investigated, their mode of inactivation by a single disinfectant
      varied. This explains why closely related viruses can exhibit drastically
      different inactivation kinetics.

PMID- 23542620
TI  - Biochemical diversity of carboxyl esterases and lipases from Lake Arreo (Spain):
      a metagenomic approach.
AB  - The esterases and lipases from the alpha/beta hydrolase superfamily exhibit an
      enormous sequence diversity, fold plasticity, and activities. Here, we present
      the comprehensive sequence and biochemical analyses of seven distinct esterases
      and lipases from the metagenome of Lake Arreo, an evaporite karstic lake in Spain
      (42 degrees 46'N, 2 degrees 59'W; altitude, 655 m). Together with oligonucleotide
      usage patterns and BLASTP analysis, our study of esterases/lipases mined from
      Lake Arreo suggests that its sediment contains moderately halophilic and cold
      adapted proteobacteria containing DNA fragments of distantly related plasmids or
      chromosomal genomic islands of plasmid and phage origins. This metagenome encodes
      esterases/lipases with broad substrate profiles (tested over a set of 101
      structurally diverse esters) and habitat-specific characteristics, as they
      exhibit maximal activity at alkaline pH (8.0 to 8.5) and temperature of 16 to 40
      degrees C, and they are stimulated (1.5 to 2.2 times) by chloride ions (0.1 to
      1.2 M), reflecting an adaptation to environmental conditions. Our work provides
      further insights into the potential significance of the Lake Arreo
      esterases/lipases for biotechnology processes (i.e., production of enantiomers
      and sugar esters), because these enzymes are salt tolerant and are active at low
      temperatures and against a broad range of substrates. As an example, the ability
      of a single protein to hydrolyze triacylglycerols, (non)halogenated alkyl and
      aryl esters, cinnamoyl and carbohydrate esters, lactones, and chiral epoxides to
      a similar extent was demonstrated.

PMID- 23542621
TI  - Genotypic diversity and virulence characteristics of clinical and environmental
      Vibrio vulnificus isolates from the Baltic Sea region.
AB  - The genetic diversity of Vibrio vulnificus isolates from clinical and
      environmental sources originating from the Baltic Sea region was evaluated by
      multilocus sequence typing (MLST), and possible relationships between MLST
      clusters, potential genotypic and phenotypic traits associated with
      pathogenicity, and source of isolation were investigated. The studied traits
      included genotyping of polymorphic loci (16S rRNA, vcg, and pilF),
      presence/absence of potential virulence genes, including nanA, nab, and genes of
      pathogenicity regions, metabolic features, hemolytic activity, resistance to
      human serum, and cytotoxicity to human intestinal cells. MLST generated 35 (27
      new) sequence types and divided the 53 isolates (including four reference
      strains) into two main clusters, with cluster I containing biotype 1 and 2
      isolates of mainly environmental origin and cluster II containing biotype 1
      isolates of mainly clinical origin. Cluster II isolates were further subdivided
      into two branches. Branch IIB included isolates from recent cases of wound
      infections that were acquired at the German Baltic Sea coastline between 2010 and
      2011 and isolates from seawater samples of the same regions isolated between 1994
      and 2010. Comparing the MLST data with the results of genotyping and phenotyping
      showed that strains of MLST cluster II possess a number of additional
      pathogenicity-associated traits compared to cluster I strains. Rapid
      microbiological methods such as matrix-assisted laser desorption ionization-time
      of flight (MALDI-TOF) mass spectrometry combined with typing of selected
      virulence-associated traits (e.g., serum resistance, mannitol fermentation, nanA,
      and pathogenicity region XII) could be used for risk assessment purposes
      regarding V. vulnificus strains isolated from the Baltic Sea region.

PMID- 23542622
TI  - Synthesis of fucosyl-N-acetylglucosamine disaccharides by transfucosylation using
      alpha-L-fucosidases from Lactobacillus casei.
AB  - AlfB and AlfC alpha-l-fucosidases from Lactobacillus casei were used in
      transglycosylation reactions, and they showed high efficiency in synthesizing
      fucosyldisaccharides. AlfB and AlfC activities exclusively produced fucosyl-alpha
      1,3-N-acetylglucosamine and fucosyl-alpha-1,6-N-acetylglucosamine, respectively.
      The reaction kinetics showed that AlfB can convert 23% p-nitrophenyl-alpha-l
      fucopyranoside into fucosyl-alpha-1,3-N-acetylglucosamine and AlfC at up to 56%
      into fucosyl-alpha-1,6-N-acetylglucosamine.

PMID- 23542619
TI  - Culture-independent analysis of aerosol microbiology in a metropolitan subway
      system.
AB  - The goal of this study was to determine the composition and diversity of
      microorganisms associated with bioaerosols in a heavily trafficked metropolitan
      subway environment. We collected bioaerosols by fluid impingement on several New
      York City subway platforms and associated sites in three sampling sessions over a
      1.5-year period. The types and quantities of aerosolized microorganisms were
      determined by culture-independent phylogenetic analysis of small-subunit rRNA
      gene sequences by using both Sanger (universal) and pyrosequencing (bacterial)
      technologies. Overall, the subway bacterial composition was relatively simple;
      only 26 taxonomic families made up ~75% of the sequences determined. The
      microbiology was more or less similar throughout the system and with time and was
      most similar to outdoor air, consistent with highly efficient air mixing in the
      system. Identifiable bacterial sequences indicated that the subway aerosol
      assemblage was composed of a mixture of genera and species characteristic of
      soil, environmental water, and human skin commensal bacteria. Eukaryotic
      diversity was mainly fungal, dominated by organisms of types associated with wood
      rot. Human skin bacterial species (at 99% rRNA sequence identity) included the
      Staphylococcus spp. Staphylococcus epidermidis (the most abundant and prevalent
      commensal of the human integument), S. hominis, S. cohnii, S. caprae, and S.
      haemolyticus, all well-documented human commensal bacteria. We encountered no
      organisms of public health concern. This study is the most extensive culture
      independent survey of subway microbiota so far and puts in place pre-event
      information required for any bioterrorism surveillance activities or monitoring
      of the microbiological impact of recent subway flooding events.

PMID- 23542623
TI  - Distinctive microbial community structure in highly stratified deep-sea brine
      water columns.
AB  - Atlantis II and Discovery are two hydrothermal and hypersaline deep-sea pools in
      the Red Sea rift that are characterized by strong thermohalo-stratification and
      temperatures steadily peaking near the bottom. We conducted comprehensive
      vertical profiling of the microbial populations in both pools and highlighted the
      influential environmental factors. Pyrosequencing of the 16S rRNA genes revealed
      shifts in community structures vis-a-vis depth. High diversity and low abundance
      were features of the deepest convective layers despite the low cell density.
      Surprisingly, the brine interfaces had significantly higher cell counts than the
      overlying deep-sea water, yet they were lowest in diversity. Vertical
      stratification of the bacterial populations was apparent as we moved from the
      Alphaproteobacteria-dominated deep sea to the Planctomycetaceae- or
      Deferribacteres-dominated interfaces to the Gammaproteobacteria-dominated brine
      layers. Archaeal marine group I was dominant in the deep-sea water and
      interfaces, while several euryarchaeotic groups increased in the brine. Across
      sites, microbial phylotypes and abundances varied substantially in the brine
      interface of Discovery compared with Atlantis II, despite the near-identical
      populations in the overlying deep-sea waters. The lowest convective layers
      harbored interestingly similar microbial communities, even though temperature and
      heavy metal concentrations were very different. Multivariate analysis indicated
      that temperature and salinity were the major influences shaping the communities.
      The harsh conditions and the low-abundance phylotypes could explain the observed
      correlation in the brine pools.

PMID- 23542624
TI  - Mountain pine beetles colonizing historical and naive host trees are associated
      with a bacterial community highly enriched in genes contributing to terpene
      metabolism.
AB  - The mountain pine beetle, Dendroctonus ponderosae, is a subcortical herbivore
      native to western North America that can kill healthy conifers by overcoming host
      tree defenses, which consist largely of high terpene concentrations. The
      mechanisms by which these beetles contend with toxic compounds are not well
      understood. Here, we explore a component of the hypothesis that beetle-associated
      bacterial symbionts contribute to the ability of D. ponderosae to overcome tree
      defenses by assisting with terpene detoxification. Such symbionts may facilitate
      host tree transitions during range expansions currently being driven by climate
      change. For example, this insect has recently breached the historical geophysical
      barrier of the Canadian Rocky Mountains, providing access to naive tree hosts and
      unprecedented connectivity to eastern forests. We use culture-independent
      techniques to describe the bacterial community associated with D. ponderosae
      beetles and their galleries from their historical host, Pinus contorta, and their
      more recent host, hybrid P. contorta-Pinus banksiana. We show that these
      communities are enriched with genes involved in terpene degradation compared with
      other plant biomass-processing microbial communities. These pine beetle microbial
      communities are dominated by members of the genera Pseudomonas, Rahnella,
      Serratia, and Burkholderia, and the majority of genes involved in terpene
      degradation belong to these genera. Our work provides the first metagenome of
      bacterial communities associated with a bark beetle and is consistent with a
      potential microbial contribution to detoxification of tree defenses needed to
      survive the subcortical environment.

PMID- 23542625
TI  - Characterization of a wild, novel nisin a-producing Lactococcus strain with an L.
      lactis subsp. cremoris genotype and an L. lactis subsp. lactis phenotype,
      isolated from Greek raw milk.
AB  - Several molecular taxonomic studies have revealed that many natural (wild)
      Lactococcus lactis strains of dairy origin which are phenotypically
      representative of the L. lactis subspecies lactis cluster genotypically within
      subspecies cremoris and vice versa. Recently, we isolated two wild nisin
      producing (Nis(+)) L. lactis strains, M78 and M104, of the lactis phenotype from
      Greek raw milk (J. Samelis, A. Lianou, A. Kakouri, C. Delbes, I. Rogelj, B. B.
      Matijasic, and M. C. Montel, J. Food Prot. 72:783-790, 2009); strain M78 possess
      a novel nisin A sequence (GenBank accession number HM219853). In this study, the
      actual subspecies identity of M78 and M104 isolates was elucidated, using 16S
      rRNA and acmA (encoding lactococcal N-acetylmuramidase) gene and histidine
      biosynthesis operon polymorphisms and 16S rRNA and ldh (encoding lactate
      dehydrogenase) gene phylogenies. Except the acmA gene analysis, molecular tools
      revealed that isolates M78 and M104 clustered with strains of the cremoris
      genotype, including the LMG 6897(T) strain, while they were distant from strains
      of the lactis genotype, including the LMG 6890(T) strain. The two wild isolates
      had identical repetitive sequence-based PCR (rep-PCR), randomly amplified
      polymorphic DNA (RAPD), plasmid, and whole-cell protein profiles and shared high
      16S rRNA (99.9%) and ldh (100%) gene sequence homologies. In contrast, they
      exhibited identical sugar fermentation and enzymatic patterns which were similar
      to those of the subspecies lactis LMG 6890(T) strain. To our knowledge, this is
      the first complete identification report on a wild L. lactis subsp. cremoris
      genotype of the lactis phenotype which is capable of nisin A production and,
      thus, has strong potential for use as a novel dairy starter and/or protective
      culture.

PMID- 23542626
TI  - Identification and expression of genes involved in the conversion of daidzein and
      genistein by the equol-forming bacterium Slackia isoflavoniconvertens.
AB  - Gut bacteria play a key role in the metabolism of dietary isoflavones, thereby
      influencing the availability and bioactivation of these polyphenols in the
      intestine. The human intestinal bacterium Slackia isoflavoniconvertens converts
      the main soybean isoflavones daidzein and genistein to equol and 5-hydroxy-equol,
      respectively. Cell extracts of S. isoflavoniconvertens catalyzed the conversion
      of daidzein via dihydrodaidzein to equol and that of genistein to
      dihydrogenistein. Growth of S. isoflavoniconvertens in the presence of daidzein
      led to the induction of several proteins as observed by two-dimensional
      difference gel electrophoresis. Based on determined peptide sequences, we
      identified a cluster of eight genes encoding the daidzein-induced proteins.
      Heterologous expression of three of these genes in Escherichia coli and enzyme
      activity tests with the resulting cell extracts identified the corresponding gene
      products as a daidzein reductase (DZNR), a dihydrodaidzein reductase (DHDR), and
      a tetrahydrodaidzein reductase (THDR). The recombinant DZNR also converted
      genistein to dihydrogenistein at higher rates than were observed for the
      conversion of daidzein to dihydrodaidzein. Higher rates were also observed with
      cell extracts of S. isoflavoniconvertens. The recombinant DHDR and THDR catalyzed
      the reduction of dihydrodaidzein to equol, while the corresponding conversion of
      dihydrogenistein to 5-hydroxy-equol was not observed. The DZNR, DHDR, and THDR
      were expressed as Strep-tag fusion proteins and subsequently purified by affinity
      chromatography. The purified enzymes were further characterized with regard to
      their activity, stereochemistry, quaternary structure, and content of flavin
      cofactors.

PMID- 23542627
TI  - Development of a reverse transcription-quantitative PCR assay for detection of
      salivirus/klassevirus.
AB  - A broadly reactive and highly sensitive reverse transcription-quantitative PCR
      assay to detect salivirus/klassevirus was developed. By means of the developed
      assay, salivirus/klassevirus was detected in 13 (93%) raw sewage, 4 (29%)
      secondary-treated sewage, and 9 (16%) river water samples, with a maximum
      concentration of 9.7 * 10(6) copies/liter.

PMID- 23542628
TI  - Physiological and transcriptional responses of Saccharomyces cerevisiae to d
      limonene show changes to the cell wall but not to the plasma membrane.
AB  - Monoterpenes can, upon hydrogenation, be used as light-fraction components of
      sustainable aviation fuels. Fermentative production of monoterpenes in engineered
      microorganisms, such as Saccharomyces cerevisiae, has gained attention as a
      potential route to deliver these next-generation fuels from renewable biomass.
      However, end product toxicity presents a formidable problem for microbial
      synthesis. Due to their hydrophobicity, monoterpene inhibition has long been
      attributed to membrane interference, but the molecular mechanism remains largely
      unsolved. In order to gain a better understanding of the mode of action, we
      analyzed the composition and structural integrity of the cell envelope as well as
      the transcriptional response of yeast cells treated with an inhibitory amount of
      d-limonene (107 mg/liter). We found no alterations in membrane fluidity,
      structural membrane integrity, or fatty acid composition after the solvent
      challenge. A 4-fold increase in the mean fluorescence intensity per cell (using
      calcofluor white stain) and increased sensitivity to cell wall-degrading enzymes
      demonstrated that limonene disrupts cell wall properties. Global transcript
      measurements confirmed the membrane integrity observations by showing no
      upregulation of ergosterol or fatty acid biosynthesis pathways, which are
      commonly overexpressed in yeast to reinforce membrane rigidity during ethanol
      exposure. Limonene shock did cause a compensatory response to cell wall damage
      through overexpression of several genes (ROM1, RLM1, PIR3, CTT1, YGP1, MLP1,
      PST1, and CWP1) involved with the cell wall integrity signaling pathway. This is
      the first report demonstrating that cell wall, rather than plasma membrane,
      deterioration is the main source of monoterpene inhibition. We show that limonene
      can alter the structure and function of the cell wall, which has a clear effect
      on cytokinesis.

PMID- 23542629
TI  - From waste to plastic: synthesis of poly(3-hydroxypropionate) in Shimwellia
      blattae.
AB  - In recent years, glycerol has become an attractive carbon source for microbial
      processes, as it accumulates massively as a by-product of biodiesel production,
      also resulting in a decline of its price. A potential use of glycerol in
      biotechnology is the synthesis of poly(3-hydroxypropionate) [poly(3HP)], a
      biopolymer with promising properties which is not synthesized by any known wild
      type organism. In this study, the genes for 1,3-propanediol dehydrogenase (dhaT)
      and aldehyde dehydrogenase (aldD) of Pseudomonas putida KT2442, propionate
      coenzyme A (propionate-CoA) transferase (pct) of Clostridium propionicum X2, and
      polyhydroxyalkanoate (PHA) synthase (phaC1) of Ralstonia eutropha H16 were cloned
      and expressed in the 1,3-propanediol producer Shimwellia blattae. In a two-step
      cultivation process, recombinant S. blattae cells accumulated up to 9.8% +/- 0.4%
      (wt/wt [cell dry weight]) poly(3HP) with glycerol as the sole carbon source.
      Furthermore, the engineered strain tolerated the application of crude glycerol
      derived from biodiesel production, yielding a cell density of 4.05 g cell dry
      weight/liter in a 2-liter fed-batch fermentation process.

PMID- 23542630
TI  - Repetitive, marker-free, site-specific integration as a novel tool for multiple
      chromosomal integration of DNA.
AB  - We present a tool for repetitive, marker-free, site-specific integration in
      Lactococcus lactis, in which a nonreplicating plasmid vector (pKV6) carrying a
      phage attachment site (attP) can be integrated into a bacterial attachment site
      (attB). The novelty of the tool described here is the inclusion of a minimal
      bacterial attachment site (attB(min)), two mutated loxP sequences (lox66 and
      lox71) allowing for removal of undesirable vector elements (antibiotic resistance
      marker), and a counterselection marker (oroP) for selection of loxP recombination
      on the pKV6 vector. When transformed into L. lactis expressing the phage TP901-1
      integrase, pKV6 integrates with high frequency into the chromosome, where it is
      flanked by attL and attR hybrid attachment sites. After expression of Cre
      recombinase from a plasmid that is not able to replicate in L. lactis, loxP
      recombinants can be selected for by using 5-fluoroorotic acid. The introduced
      attB(min) site can subsequently be used for a second round of integration. To
      examine if attP recombination was specific to the attB site, integration was
      performed in strains containing the attB, attL, and attR sites or the attL and
      attR sites only. Only attP-attB recombination was observed when all three sites
      were present. In the absence of the attB site, a low frequency of attP-attL
      recombination was observed. To demonstrate the functionality of the system, the
      xylose utilization genes (xylABR and xylT) from L. lactis strain KF147 were
      integrated into the chromosome of L. lactis strain MG1363 in two steps.

PMID- 23542631
TI  - Prevalence and genetic characterization of Toxoplasma gondii in bats in Myanmar.
AB  - We detected Toxoplasma gondii in 29.3% (95% confidence interval [CI], 25.5% to
      33.1%) of 550 insectivorous bats collected in Myanmar. The genotyping of these
      positive samples revealed they were closely related to or belong to clonal type
      I, which is highly virulent in mice, showing that these bats are potential
      reservoirs for T. gondii transmission.

PMID- 23542632
TI  - Telomere shortening in Ph-negative chronic myeloproliferative neoplasms: a
      biological marker of polycythemia vera and myelofibrosis, regardless of
      hydroxycarbamide therapy.
AB  - The purpose of this study was to investigate telomere length (TL) in Ph-negative
      chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association
      of TL with disease progression and hydroxycarbamide (HU) treatment. TL was
      analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs,
      including polycythemia vera (PV), essential thrombocythemia and myelofibrosis
      (MF), and compared with age-matched healthy control subjects (CTR), along with
      some cases of secondary erythrocytosis (SE). More than half of the patients with
      CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis.
      JAK2 mutation analysis was performed as well. TL was significantly shortened in
      patients with CMN compared with CTR (p < 0.0001). PV and MF showed the most
      pronounced decrease (p < 0.0001), whereas both essential thrombocythemia and SE
      showed no significant difference in TL compared with CTR. A short TL correlated
      with JAK2-V617F allele burden greater than 50% (p = 0.0025), age (p = 0.0132) and
      diagnosis of PV (p = 0.0122). No correlation was found with disease duration,
      history of thrombosis, cytoreductive treatment, antiaggregation agents, adverse
      cytogenetics, phlebotomies, or time to evolution to MF. In summary, TL is
      distinctly shortened in PV and MF, and it inversely correlates with JAK2V617F
      allele burden. In addition, HU is unlikely to contribute to telomere erosion.
      Lastly, PV and SE significantly differ in TL. Therefore, TL could be an
      additional diagnostic marker to identify and monitor Ph-neg-CMN patients. 

PMID- 23542633
TI  - In vitro anthelmintic efficacy of Carex baccans (Cyperaceae): ultrastructural,
      histochemical and biochemical alterations in the cestode, Raillietina
      echinobothrida.
AB  - The aqueous juice of the root extract of Carex baccans (Family: Cyperaceae) is
      used as an anthelmintic in Meghalaya, India. The present investigation was
      carried out to evaluate the extent of ultrastructural, histochemical and
      biochemical alterations caused by the plant derived component(s) on Raillietina
      echinobothrida, a cestode parasite of domestic fowl. Live tapeworms, collected
      from the freshly slaughtered host, were exposed to different concentrations of
      the crude ethanolic root extract of C. baccans for varying time durations. The
      treated parasites revealed complete inactivation and flaccid paralysis leading to
      death; they were processed for ultrastructural, histochemical and biochemical
      observations, as soon as paralysis set in. Compared to controls, the treated
      parasites showed extensive distortion and destruction of the surface fine
      topography of the tegument, erosion of microtriches, disruption of muscle layers,
      intense vacuolization of tegumental and subtegumental layers, swelling and
      vacuolization of mitochondria and a significantly reduced activity of tegumental
      enzymes like AcPase and AlkPase. Phytochemicals from the root of C. baccans seem
      to be effective against soft-bodied cestode parasites and need to be
      characterized and identified.

PMID- 23542634
TI  - Live imaging of drug responses in the tumor microenvironment in mouse models of
      breast cancer.
AB  - The tumor microenvironment plays a pivotal role in tumor initiation, progression,
      metastasis, and the response to anti-cancer therapies. Three-dimensional co
      culture systems are frequently used to explicate tumor-stroma interactions,
      including their role in drug responses. However, many of the interactions that
      occur in vivo in the intact microenvironment cannot be completely replicated in
      these in vitro settings. Thus, direct visualization of these processes in real
      time has become an important tool in understanding tumor responses to therapies
      and identifying the interactions between cancer cells and the stroma that can
      influence these responses. Here we provide a method for using spinning disk
      confocal microscopy of live, anesthetized mice to directly observe drug
      distribution, cancer cell responses and changes in tumor-stroma interactions
      following administration of systemic therapy in breast cancer models. We describe
      procedures for labeling different tumor components, treatment of animals for
      observing therapeutic responses, and the surgical procedure for exposing tumor
      tissues for imaging up to 40 hours. The results obtained from this protocol are
      time-lapse movies, in which such processes as drug infiltration, cancer cell
      death and stromal cell migration can be evaluated using image analysis software.

PMID- 23542635
TI  - Studies on the arginase, 5'-nucleotidase and lysozyme activity by monocytes from
      visceral leishmaniasis patients.
AB  - Intracellular pathogenic protozoan infection like visceral leishmaniasis is
      considered in terms of the overall inflammatory response and the complex cellular
      interactions leading to formation of the activated macrophage. Analysis of the
      development of activation is facilitated when operationally defined stage of
      activation are characterized using a library of objective markers. There is a
      role of arginase in the immune response supporting its involvement in macrophage
      effector mechanism in vitro and in vivo. 5'-Nucleotidase a plasma membrane
      component has been cited as a biochemical correlate of macrophage function in an
      altered morphological and biochemical state of activation and stimulation.
      Depression in 5'-nucleotidase activity has been generally referred to as a
      characteristic marker of activated macrophages. Lysozyme or lysosomal enzymes are
      released into the endocytic or autophagic vacuole macrophage where they serve the
      purpose of intracellular digestion of engulfed or segregated materials. In the
      present study, we have studied levels of arginase and 5'-nucleotidase (marker for
      macrophage activation) in monocytes of active VL patients and healthy controls.
      Lysozyme a secretary product of macrophages was also measured in supernatants
      collected from monocytes of active VL patients and healthy controls. Elevated
      levels of 5'-nucleotidase were observed in supernatants of monocytes from active
      VL patients as compared to healthy controls. Low levels of arginase and lysozyme
      production by monocytes isolated from VL patients were observed as compared to
      healthy controls. Our studies suggest that low levels of arginase and elevated 5'
      nucleotidase activity could be one of the mechanisms in the pathology of VL
      infection. Low lysozyme activity in patients may account for persistence of
      Leishmania parasites in VL infections.

PMID- 23542636
TI  - Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients
      hospitalized for suspected tuberculosis in Uganda.
AB  - BACKGROUND: Cryptococcal infection occurs in HIV-seropositive patients and is
      associated with high mortality. However, limited information is available on the
      prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV
      seropositive patients in sub-Saharan Africa. OBJECTIVES: To determine the
      prevalence of and risk factors for cryptococcal antigenemia among HIV
      seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with
      unexplained cough >=2 weeks and suspected tuberculosis (TB) and also to determine
      if antigenemia is associated with an increased mortality. METHODS: Between
      September 2009 and September 2010, we enrolled consecutive HIV-seropositive
      adults hospitalized at Mulago Hospital with cough >=2 weeks and suspected TB.
      Banked serum was tested for cryptococcal antigen. We compared demographic and
      clinical characteristics, and 2-month mortality in patients with and without
      cryptococcal antigenemia. RESULTS: Of 563 HIV-seropositive patients, 32 (5.7%)
      were cryptococcal antigen (CrAg) positive. None had Cryptococcus neoformans
      detected on fungal culture of bronchoalveolar lavage fluid (n = 116). CrAg
      positive patients had a lower median CD4 count compared with CrAg-negative
      patients (25 vs. 55 cells/MUL, P = 0.02), and a substantial proportion of CrAg
      positive patients also had concurrent TB (31%). A positive CrAg test was not
      associated with increased mortality during the 2-month follow-up period (hazard
      ratio: 0.99, 95% confidence interval: 0.63 to 1.54, P = 0.95) after adjusting for
      CD4 count and antiretroviral therapy use at enrollment and/or follow-up.
      CONCLUSIONS: Occult cryptococcal antigenemia occurs commonly among hospitalized
      HIV-seropositive patients with suspected TB. CrAg testing should be considered in
      hospitalized HIV-seropositive patients with CD4 count <50 cells/MUL, coupled with
      longer follow-up to evaluate the diagnostic value of CrAg and therapeutic
      interventions in patients with asymptomatic cryptococcal antigenemia.

PMID- 23542637
TI  - High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose
      acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover
      trial.
AB  - BACKGROUND: Standard doses of herpes simplex virus (HSV) suppressive therapy
      reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV
      1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct
      inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV
      associated inflammation. We hypothesized that high-dose valacyclovir would
      further reduce plasma HIV-1 RNA and that the effect would be mediated by greater
      suppression of HSV shedding. METHODS: Thirty-four participants with HIV-1 and HSV
      2 not on antiretroviral therapy were enrolled into a randomized, open-label
      crossover trial of valacyclovir 1000 mg twice daily or acyclovir 400 mg twice
      daily for 12 weeks, followed by a 2-week washout, and then the alternate
      treatment arm for 12 weeks. HSV DNA was measured from daily self-collected
      genital swabs for the initial 4 weeks of each arm, and HIV-1 RNA was quantified
      from weekly plasma samples. RESULTS: Twenty-eight participants provided plasma
      samples and genital swabs on both acyclovir and valacyclovir. The genital HSV-2
      shedding rate was the same on valacyclovir and acyclovir [7.8% vs. 8.2% of days;
      relative risk: 0.95; 95% confidence interval (CI): 0.66 to 1.37; P = 0.78].
      Plasma HIV-1 RNA was 0.27 log10 copies per milliliter lower on valacyclovir
      compared with acyclovir (95% CI: -0.41 to -0.14 log10 copies per milliliter; P <
      0.001); this was unchanged after adjustment for genital HSV-2 shedding.
      CONCLUSIONS: High-dose valacyclovir reduces plasma HIV-1 RNA levels more than
      standard-dose acyclovir in HIV-1/HSV-2-seropositive persons not receiving
      antiretroviral therapy. The incremental reduction in plasma HIV-1 RNA achieved is
      not mediated by greater genital HSV-2 suppression.

PMID- 23542638
TI  - Pooled HIV-1 RNA viral load testing for detection of antiretroviral treatment
      failure in Kenyan children.
AB  - BACKGROUND: Pooled viral load (VL) testing with 2 different testing strategies
      was evaluated as a potential cost saving method to monitor antiretroviral therapy
      (ART) in HIV-infected children receiving ART in a resource-limited setting.
      METHODS: Archived samples collected from 250 HIV-1-infected children on first
      line ART at various time points post-ART initiation were evaluated for pooled VL
      testing using a minipool + algorithm strategy. Additionally, samples collected in
      real time from 125 children on ART were assessed for virologic failure using a
      minipool strategy for pooled VL testing. Virologic failure was determined as HIV
      1 RNA VLs >1500 copies/mL. RESULTS: Minipool + algorithm strategy for pooled VL
      testing of archived samples had estimated viral failure of 13.6%, with a relative
      efficiency (RE) of 23.6% (95% CI: 18.5 to 29.4), and negative predictive value of
      88%. This testing strategy would have resulted in 24% fewer assays needed for a
      cost savings of $1180 per 100 samples. The minipool strategy for pooled VL
      testing of samples obtained in real time yielded an estimated 23.2% of samples
      with viral failure and a RE of 8.0% (95% CI: 3.9 to 14.2); however, had a
      minipool + algorithm pooling strategy been used, the RE would have increased to
      20%. CONCLUSIONS: The minipool + algorithm strategy for pooled VL testing to
      detect virologic failure in HIV-1-infected children on ART was determined to be
      relatively efficient in detecting virologic failure, have high negative
      predictive value, with substantial cost savings. Pooling strategies may be
      important components of cost-effect strategies to reduce rates of viral failure
      and resistance, thus, improving clinical outcomes.

PMID- 23542641
TI  - A curious case of hyperbilirubinemia.
AB  - A 60-year-old patient suffering from easy fatigability was noted to have high
      total but normal conjugated bilirubin level though serum colour was pale. On
      further investigation the patient was found to be suffering from multiple myeloma
      and gamma globulin was possibly interfering with total bilirubin estimation.

PMID- 23542639
TI  - No clinically significant drug-resistance mutations in HIV-1 subtype C-infected
      women after discontinuation of NRTI-based or PI-based HAART for PMTCT in
      Botswana.
AB  - Risk of developing drug resistance after stopping antiretroviral regimens to
      prevent mother-to-child HIV-1 transmission is unknown. The Mma Bana Study
      randomized treatment-naive pregnant women with CD4 >=200 cells per cubic
      millimeter to receive either abacavir/zidovudine/lamivudine [triple nucleoside
      reverse transcriptase inhibitor (NRTI) arm] or
      lopinavir/ritonavir/zidovudine/lamivudine [protease inhibitor (PI) arm]. Drugs
      were discontinued after 6 months of breastfeeding. One month after
      discontinuation, 29 NRTI arm samples and 25 PI arm samples were successfully
      genotyped. No clinically significant antiretroviral resistance mutations were
      detected. Eight minor resistance mutations were found among 11 (20%) women (3
      from NRTI arm and 8 from PI arm), occurring at similar frequencies to those
      reported in HIV-1 subtype C treatment-naive cohorts.

PMID- 23542640
TI  - Identification of 3 distinct HIV-1 founding strains responsible for expanding
      epidemic among men who have sex with men in 9 Chinese cities.
AB  - OBJECTIVES: To investigate the epidemiological relationships between HIV-1
      strains that are spread among the men who have sex with men (MSM) populations of
      9 cities across China and to analyze the origins and divergence times of the
      major epidemic strains found in the MSM population. METHODS: A total of 583 HIV-1
      positive subjects were recruited from high-risk MSM populations in 9 cities
      across China between 2009 and 2011. Nucleotide sequences of 1.0-kb pro-RT regions
      were amplified and sequenced. Phylogenetic and Bayesian molecular clock analyses
      were performed. RESULTS: The overall distribution of HIV-1 genotypes was as
      follows: CRF01_AE, 62.1%; CRF07_BC, 18.2%; subtype B (United States-European),
      15.9%; subtype B', 0.7%; other recombinants, 3.1%. In addition to the 2 distinct
      CRF01_AE clusters [cluster 1 (n = 157, 26.9%) and cluster 2 (n = 196, 33.6%)]
      previously reported by our group, we identified a novel CRF07_BC cluster (cluster
      3) (n = 94, 16.1%) unique to China's MSM population whose strains were homologous
      and could be detected in all 9 cities. These 3 lineages of HIV-1 strains
      (clusters 1-3) accounted for 76.7% (447 of 583) of infections among MSM in China
      as a whole. Clusters 1, 2, and 3 were estimated to have been introduced into the
      MSM population in 1999, 2001, and 2001, respectively, indicating that the newly
      identified CRF07_BC cluster 3 is not a young lineage. However, it spread quickly
      in recent years. CONCLUSIONS: We identified 3 distinct HIV-1 lineages (clusters 1
      3) responsible for the recent upsurge of the AIDS epidemic among MSM in China.
      These 3 HIV-1 variants are spread widely among MSM throughout China,
      demonstrating remarkable founding effects.

PMID- 23542642
TI  - The use of abdominal free fat for volumetric augmentation and primary dural
      closure in supratentorial skull base surgery: managing the stigma of a temporal
      defect.
AB  - The most prominent stigma of supratentorial skull base surgery is the defect
      caused by wasting of the temporalis muscle by denervation, devascularization, or
      rotation of the muscle. Any of the above may lead to a unilateral temporal
      deformity informally referred to patients as "the divot in my head." Abdominal
      free fat grafting has been used by surgeons for years to close posterior fossa
      defects with excellent results. We present our experience using abdominal free
      fat grafts to improve cosmetic results and to prevent cerebrospinal fluid leaks
      in supratentorial skull base surgery. The basic technique and its benefits are
      described.

PMID- 23542643
TI  - A cell-cell communication signal integrates quorum sensing and stress response.
AB  - Pseudomonas aeruginosa uses a hierarchical quorum sensing (QS) network consisting
      of las, pqs and rhl regulatory elements to coordinate the expression of bacterial
      virulence genes. However, clinical isolates frequently contain loss-of-function
      mutations in the central las system. This motivated us to search for a mechanism
      that may functionally substitute las. Here we report identification of a new QS
      signal, IQS. Disruption of IQS biosynthesis paralyzes the pqs and rhl QS systems
      and attenuates bacterial virulence. Production of IQS is tightly controlled by
      las under normal culture conditions but is also activated by phosphate
      limitation, a common stressor that bacteria encounter during infections. Thus,
      these results have established an integrated QS system that connects the central
      las system and phosphate-stress response mechanism to the downstream pqs and rhl
      regulatory systems. Our discovery highlights the complexity of QS signaling
      systems and extends the gamut of QS and stress-response mechanisms.

PMID- 23542645
TI  - Popular misconceptions regarding the diabetes management: where should we focus
      our attention?
AB  - BACKGROUND: Diabetes mellitus is a universal health problem with a global
      prevalence of 1.3%. India is known as the "Diabetes capital of the world" as it
      harbours the largest number of diabetes patients. There is lack of awareness
      about the existing interventions for preventing diabetes and for the management
      of the complications. One of the barriers in the way of seeking health care
      advice is the misconception about the disease, which revolves around all the
      aspects of diabetes, which include its prevention, control and treatment.
      OBJECTIVES: To determine the various misconceptions about the management of
      Diabetes mellitus in the study area.To find out the association of various
      misconceptions with the socio-demographic factors. MATERIAL AND METHODS: A cross
      sectional study was conducted at the Urban Health Centre (UHC) Ariankuppam,
      Pondicherry. A total of 406 adult patients were interviewed. A pretested, semi
      structured interview schedule was developed in the local language, and it was
      utilized to collect the data. The collected interview schedules were scrutinized
      for the accuracy of the information which was provided and for any lacunae. The
      compilation and analysis were carried out with the help of the Epi- Info
      software. The T test and the Chi-square test were used according to the
      distribution of the data, to see the associations of the different factors.
      RESULTS: The commonest misconceptions were "Diabetes can be cured by herbal
      treatment" (46.6%) and "Bitter foods reduce the elevated blood sugar levels"
      (46.6%). The misconception, "The treatment should be stopped if the diabetes is
      controlled for few months" significantly decreased with advancing age. There were
      no significant differences between females and males when the various
      misconceptions were compared. The commonest misconception among females was
      "Bitter foods reduce the elevated blood sugar levels" (49.4%) and among males, it
      was "Diabetes can be cured by herbal treatment" (47.9%). When the misconceptions
      were compared, it was found that there were significant differences between the
      subjects who belonged to different religions. CONCLUSION: The misconceptions
      regarding the diabetes management in the general population, irrespective of the
      education and particularly among the Muslim community, were widespread. A
      majority of these misconceptions were diet and drug related.

PMID- 23542644
TI  - Two Fe-S clusters catalyze sulfur insertion by radical-SAM
      methylthiotransferases.
AB  - How living organisms create carbon-sulfur bonds during the biosynthesis of
      critical sulfur-containing compounds is still poorly understood. The
      methylthiotransferases MiaB and RimO catalyze sulfur insertion into tRNAs and
      ribosomal protein S12, respectively. Both belong to a subgroup of radical-S
      adenosylmethionine (radical-SAM) enzymes that bear two [4Fe-4S] clusters. One
      cluster binds S-adenosylmethionine and generates an Ado* radical via a well
      established mechanism. However, the precise role of the second cluster is
      unclear. For some sulfur-inserting radical-SAM enzymes, this cluster has been
      proposed to act as a sacrificial source of sulfur for the reaction. In this
      paper, we report parallel enzymological, spectroscopic and crystallographic
      investigations of RimO and MiaB, which provide what is to our knowledge the first
      evidence that these enzymes are true catalysts and support a new sulfation
      mechanism involving activation of an exogenous sulfur cosubstrate at an
      exchangeable coordination site on the second cluster, which remains intact during
      the reaction.

PMID- 23542646
TI  - IgG4-related systemic sclerosing disease: a diagnosis to be considered!!
AB  - IgG4-related systemic sclerosing disease is a chronic autoimmune disorder with
      diverse clinical presentation. We report a 56-year-old patient who has presented
      with obstructive jaundice, bulky pancreas and mesenteric lymph node mass. He was
      later diagnosed to have IgG4-sclerosing disease involving pancreas, small bowel
      mesentery, common bile duct, liver, gallbladder and submandibular salivary glands
      and has required multiple surgical interventions. IgG4-related systemic
      sclerosing disease appears to be more commonly encountered than it was once
      thought and needs considered in patients presenting with pancreatitis of no
      obvious underlying cause. Although the disease is primarily managed by medical
      therapy, there is a role for surgical intervention in order to obtain tissue for
      diagnosis, exclude other possible neoplastic aetiology and to manage disease
      related complications.

PMID- 23542647
TI  - Florid skin rash in acute myeloid leukaemia.

PMID- 23542648
TI  - Transvenous Onyx embolization of a subependymal deep arteriovenous malformation
      with a single drainage vein: technical note.
AB  - Cerebral arteriovenous malformations (AVMs) are uncommon. Treatment options
      include embolization, radiosurgery and surgery, separately or combined, the final
      goal being complete occlusion of the malformation. We describe the case of a
      symptomatic small subependymal AVM with a single deep drainage vein previously
      treated unsuccessfully by radiosurgery and transarterial embolization. The AVM
      was successfully embolized transvenously using Onyx, achieving complete occlusion
      in a single treatment session.

PMID- 23542649
TI  - Carotenoids in unexpected places: gall midges, lateral gene transfer, and
      carotenoid biosynthesis in animals.
AB  - Carotenoids are conjugated isoprenoid molecules with many important physiological
      functions in organisms, including roles in photosynthesis, oxidative stress
      reduction, vision, diapause, photoperiodism, and immunity. Until recently, it was
      believed that only plants, microorganisms, and fungi were capable of synthesizing
      carotenoids and that animals acquired them from their diet, but recent studies
      have demonstrated that two arthropods (pea aphid and spider mite) possess a pair
      of genes homologous to those required for the first step of carotenoid
      biosynthesis. Absent in all other known animal genomes, these genes appear to
      have been acquired by aphids and spider mites in one or several lateral gene
      transfer events from a fungal donor. We report the third case of fungal
      carotenoid biosynthesis gene homologs in an arthropod: flies from the family
      Cecidomyiidae, commonly known as gall midges. Using phylogenetic analyses we show
      that it is unlikely that lycopene cyclase/phytoene synthase and phytoene
      desaturase homologs were transferred singly to an ancient arthropod ancestor;
      instead we propose that genes were transferred independently from related fungal
      donors after divergence of the major arthropod lineages. We also examine
      variation in intron placement and copy number of the carotenoid genes that may
      underlie function in the midges. This trans-kingdom transfer of carotenoid genes
      may represent a key innovation, underlying the evolution of phytophagy and plant
      galling in gall midges and facilitating their extensive diversification across
      plant lineages.

PMID- 23542650
TI  - On the limitations of standard statistical modeling in biological systems: a full
      Bayesian approach for biology.
AB  - One of the most important scientific challenges today is the quantitative and
      predictive understanding of biological function. Classical mathematical and
      computational approaches have been enormously successful in modeling inert
      matter, but they may be inadequate to address inherent features of biological
      systems. We address the conceptual and methodological obstacles that lie in the
      inverse problem in biological systems modeling. We introduce a full Bayesian
      approach (FBA), a theoretical framework to study biological function, in which
      probability distributions are conditional on biophysical information that
      physically resides in the biological system that is studied by the scientist. 

PMID- 23542651
TI  - Three novel cytochrome P450 genes identified in the marine polychaete Perinereis
      nuntia and their transcriptional response to xenobiotics.
AB  - Polychaetes have previously been used as bioindicators of environmental
      pollution. Their ability to eliminate organic pollutants such as polycyclic
      aromatic hydrocarbons (PAH) has been extensively analyzed. However, the
      cytochrome P450 monooxygenases (CYP) genes in polychaetes, which catalyze the
      first step of oxidative degradation of PAHs, have received little attention.
      Based on the partial sequences of three CYP genes that were enriched by
      subtractive cDNA libraries of the polychaete Perinereis nuntia, we amplified and
      sequenced the full-length cDNA of these novel CYP genes. These genes were named
      CYP4BB2, CYP423A1 and CYP424A1 by the Cytochrome P450 Nomenclature Committee. The
      deduced amino acid sequence of CYP4BB2 in P. nuntia showed 68% sequence identity
      to CYP4BB1 in Nereis virens, and was listed as a new member of the CYP4BB
      subfamily. The sequence of CYP423A1 and CYP424A1 both share less than 40%
      sequence identity to all known CYP enzymes and were classed into new CYP
      families. CYP family members are composite parts of a larger group called a clan.
      CYP4BB2 and CYP424A1 are listed as CYP4 clan members, while CYP423A1 is of the
      CYP2 clan. The 3D structures of these P. nuntia CYPs were successfully predicted
      by homology-modeling using the SWISS-MODEL workspace. The models of CYP424A1 and
      CYP4BB2 were created using 1jpzB (CYP102A) as a template, while CYP423A1 utilized
      3czhB (CYP2R1) as its template. The presence of characteristic CYP superfamily
      motifs, such as the F-G?C-G amino acid sequence, and the conservation of the
      three-dimensional CYP structure shown by the modeling, suggested that these novel
      P. nuntia CYP genes may contain conserved functional domains of CYP
      monooxygenases. To examine the effect of xenobiotics on living organisms, we
      analyzed the transcriptional levels of these three new CYP genes in sandworms (P.
      nuntia) exposed to seawater artificially contaminated with benzo[a]pyrene (BaP).
      We also exposed individuals to industrial wastewater collected from Quanzhou Bay,
      Fujian, China, which was known to be contaminated with PAHs. Worms exposed to BaP
      had significantly higher levels of CYP4BB2, CYP423A1 and CYP424A1 mRNA.
      Transcription was up-regulated 5.9-, 5.3- and 12.3-folds respectively compared
      with the control worms living in clean seawater. The transcriptional levels of
      CYPs in worms cultured in the diluted wastewater collected from Quanzhou Bay, all
      positively correlated with the levels of PAHs detected in the water. The
      transcriptional up-regulation of the three CYP genes observed in this study,
      suggest the monooxygenases encoded by these CYP genes may play an important role
      in the detoxification of PAHs in this polychaete worm. These CYPs maybe essential
      for the adaptation of worms to contaminated environments and may be useful in the
      assessment of xenobiotic exposure.

PMID- 23542652
TI  - The effects of 17-alpha-ethinylestradiol (EE2) on molecular signaling cascades in
      mummichog (Fundulus heteroclitus).
AB  - Exposures to <=10 ng/L of 17-alpha-ethinylestradiol (EE2) will reduce or shut
      down egg production in freshwater fish models, while mummichog (Fundulus
      heteroclitus), an estuarine species, are able to produce eggs at EE2
      concentrations >3000 ng/L. The objective of this study was to gain mechanistic
      insight into how mummichog are able to produce eggs during exposures to high EE2.
      Mummichog were exposed to 0, 50 or 250 ng/L of EE2 for 14 d. There were no
      changes in gonadosomatic index, liversomatic index, gonad development, or plasma
      estradiol levels after exposure to EE2. However, testosterone significantly
      decreased with EE2 exposures (50, 250 ng/L). Microarray analysis in the liver
      revealed that cell processes associated with lipids were affected by EE2 at the
      transcriptome level. Based on the transcriptomics data, we hypothesize that
      mummichog are able to maintain lipid transport and uptake into the ovary and this
      may be associated with apolipoproteins, facilitating normal oocyte development.
      Novel gene regulatory networks for protein modification targets were also
      constructed to learn more about the potential roles of estrogens in the teleost
      liver. Although post-translational modifications (PTMs) are important regulatory
      mechanisms, the roles of PTMs in protein regulation in fish and the
      susceptibility of PTMs to aquatic pollutants are largely unexplored and may offer
      novel insight into mechanisms of endocrine disruption.

PMID- 23542653
TI  - New rectal construction after abdominoperineal resection for carcinoma rectum.
AB  - The results of the new reconstruction of the rectum after Abdominoperineal
      Resection (APR) with 'S'-trap arrangement of the colon and continent perineal
      colostomy controlled by adynamic bilateral graciloplasty are evaluated. The fully
      stretched gracilis muscles were utilized for occlusion of the lumen of the colon.
      METHODS AND MATERIALS: Between April 1993 and December 2006, selected 42 patients
      (30 males and 12 females) with median age of 43.5 years (25-64 years) were
      treated by a one-stage procedure without colonic diversion. All patients were
      suffering from adenocarcinoma of the lower third of the rectum. The
      abdominoperineal resection was carried out in all cases. A 25-cm-long vascular
      segment of the colon was installed in the sacral curve and 'S'-shaped trap was
      developed with fixed colonic curves at the coccyx and to the left ischial rami of
      the pubic bone. The left gracilis was wrapped around just distal to the fixed
      curve of the colon to the left ischial rami and right one around the perineal
      colostomy with different grades of tightness. Continence was satisfactory in 34
      patients; they could hold more than 1,000 ml of saline. Occasional soiling was
      reported in the night in 8 patients. All patients have achieved near-natural
      continence. The new rectal reconstruction with 'S' arrangement of colon and
      continent perineal colostomy achieved near-natural continence in 66% of cases.

PMID- 23542654
TI  - Diagnosis and management of perineurial (Tarlov) cysts in two dogs.

PMID- 23542655
TI  - Ketamine-medetomidine regimen for chemical immobilisation of free-ranging
      chimpanzees (Pan troglodytes schweinfurthii) in Uganda.

PMID- 23542656
TI  - Erysipelas in laying hens is associated with housing system.
AB  - Following the change from conventional cages to non-cage housing systems and
      furnished cages, which in Sweden was finalised by 2005, problems caused by
      Erysipelothrix rhusiopathiae increased in laying hen flocks. This study aimed to
      investigate possible associations between housing systems for laying hens and
      outbreaks of erysipelas. Also, sera from 129 flocks in different housing systems,
      collected during 2005-2007, were analysed for the presence of antibodies to E
      rhusiopathiae using an indirect ELISA test. Antibodies were detected in all
      housing systems. The mean flock absorbance values from free-range flocks were
      significantly higher than corresponding values from other housing systems. Data
      on the Swedish laying hen population were compared with the recorded number of
      erysipelas outbreaks during 1998-2011. Outbreaks occurred on 15 farms with indoor
      litter-based systems (n=87 farms in 2011). No outbreak was diagnosed on farms
      with flocks in conventional or furnished cages. The results indicate that the
      risk for an outbreak was higher in free-range systems than in indoor litter-based
      systems, and lowest for flocks housed in cages. Absence of erysipelas in the
      majority of subsequent flocks on the affected farms suggested that proper
      measures, including vaccination, were undertaken.

PMID- 23542657
TI  - Evaluation of 3-methylhistidine levels in dogs with chronic mitral valve disease.

PMID- 23542658
TI  - Detection of Agamid Adenovirus-1 in clinically healthy bearded dragons (Pogona
      vitticeps) in the UK.

PMID- 23542659
TI  - Effect of sex steroid hormones on replication and transmission of major HIV
      subtypes.
AB  - BACKGROUND: The HIV epidemic is expanding worldwide with an increasing number of
      distinct viral subtypes and circulating recombinant forms (CRFs). Out of 34
      million adults living with HIV and AIDS, women account for one half of all HIV-1
      infections worldwide. These gender differences in HIV pathogenesis may be
      attributed to sex hormones. Little is known about the role of sex hormone effects
      on HIV Subtypes pathogenesis. The aim of our study was to determine sex hormone
      effects on replication and transmissibility of HIV subtypes. METHODS: Peripheral
      blood mononuclear cells (PBMC) and monocyte derived dendritic cells (MDDC) from
      male and female donors were infected with HIV subtypes A-D and CRF02_AG,
      CRF01_AE, MN (lab adapted), Group-O, Group-N and HIV-2 at a concentration of
      5ng/ml of p24 or p27. Virus production was evaluated by measuring p24 and p27
      levels in culture supernatants. Similar experiments were carried out in the
      presence of physiological concentrations of sex steroid hormones. R5/X4
      expressions measured by flow cytometry and transmissibility was evaluated by
      transfer of HIV from primary dendritic cells (DC) to autologous donor PBMC.
      RESULTS: Our results from primary PBMC and MDDC from male and female donors
      indicate in the absence of physiological concentrations of hormone treatment
      virus production was observed in three clusters; high replicating virus (subtype
      B and C), moderate replicative virus (subtype A, D, CRF01_AE, Group_N) and least
      replicative virus (strain MN). However, dose of sex steroid hormone treatment
      influenced HIV replication and transmission kinetics in PBMC, DCs and cell lines.
      Such effects were inconsistent between donors and HIV subtypes. Sex hormone
      effects on HIV entry receptors (CCR5/CXCR4) did not correlate with virus
      production. CONCLUSIONS: Subtypes B and C showed higher replication in PBMC from
      males and females and were transmitted more efficiently through DC to male and
      female PBMC compared with other HIV-1 subtypes, HIV-1 Group O and HIV-2. These
      findings are consistent with increased worldwide prevalence of subtype B and C
      compared to other subtypes. Sex steroid hormones had variable effect on
      replication or transmission of different subtypes. These findings suggest that
      subtype, gender and sex hormones may play a crucial role in the replication and
      transmission of HIV.

PMID- 23542660
TI  - Major enzymes controlling the androgenic pressure in the developing lung.
AB  - A sex difference is observed in the incidence and morbidity of respiratory
      distress syndrome (RDS) of the neonate and in bronchopulmonary dysplasia (BPD).
      The involvement of androgens is well evidenced in RDS and it is suspected in BPD.
      Interestingly, the developing lung is not an inert tissue just exposed to
      circulating androgens, but is rather an active androgen metabolizing tissue,
      expressing enzymes involved in both androgen synthesis and inactivation. The
      present review focuses on the major enzymes involved in androgen metabolism
      within the developing lung. Testosterone synthesis and inactivation by
      AKR1C3/Akr1c6 (human/mouse 17beta-hydroxysteroid dehydrogenases (HSDs) type 5)
      and HSD17B2 (17beta-HSD type 2), respectively, play an important role in the
      developing lung. Akr1c14 (3alpha-HSD) shows a strong increase in expression
      according to developmental time. The canalicular stage of lung development
      corresponding to the surge of surfactant lipid synthesis, which is linked to RDS,
      as well as saccularization/alveolarization, which are linked to BPD, are covered
      by this review for the mouse and human species. The androgen metabolizing enzymes
      expressed within the developing lung can become potential pharmaceutical targets
      in the objective of accelerating lung maturation by specific treatments. The
      classic deleterious effects of androgens on lung maturation and the surge of
      surfactant synthesis in males are well known. Conversely, androgens also have
      positive impacts on the development of both male and female lungs. Steroidogenic
      enzymes are key regulators of these positive effects. This article is part of a
      Special Issue entitled 'CSR 2013'. 

PMID- 23542661
TI  - Cross-talk between GPER and growth factor signaling.
AB  - G protein-coupled receptors (GPCRs) and growth factor receptors mediate multiple
      physio-pathological responses to a diverse array of extracellular stimuli. In
      this regard, it has been largely demonstrated that GPCRs and growth factor
      receptors generate a multifaceted signaling network, which triggers relevant
      biological effects in normal and cancer cells. For instance, some GPCRs
      transactivate the epidermal growth factor receptor (EGFR), which stimulates
      diverse transduction pathways leading to gene expression changes, cell migration,
      survival and proliferation. Moreover, it has been reported that a functional
      interaction between growth factor receptors and steroid hormones like estrogens
      is involved in the growth of many types of tumors as well as in the resistance to
      endocrine therapy. This review highlights recent findings on the cross-talk
      between a member of the GPCR family, the G protein-coupled estrogen receptor 1
      (GPER, formerly known as GPR30) and two main growth factor receptors like EGFR
      and insulin-like growth factor-I receptor (IGF-IR). The biological implications
      of the functional interaction between these important mediators of cell responses
      particularly in cancer are discussed. This article is part of a Special Issue
      entitled 'CSR 2013'. 

PMID- 23542662
TI  - An efficient and mass reproducible method for vitrifying mouse embryos on a paper
      in cryotubes.
AB  - To date, the most successful and popular vitrification method is based on the
      minimum volume cooling (MVC) concept, in which embryos are vitrified in a very
      small volume of vitrification solution (VS) and then stored in cryotubes in
      liquid nitrogen (LN2). Unfortunately, these methods need special devices and may
      not be suitable for vitrifying a large number of embryos. Theoretically, more
      embryos in VS on a paper (MVC concept) in cryotubes can be vitrified effectively.
      Therefore, this study directly vitrifies mouse embryos on a Kimwipes tissue in an
      1.8 mL cryotube. The ICR 2-celled to blastocyst embryos were used for testing
      this procedure. In Treatment 1, embryos transferred with 1-2 MUL of VS into a
      cryotube. Treatment 2 was similar to Treatment 1 except that the cryotube was
      filled with LN2. Treatment 3 was identical to Treatment 1 except that a small
      piece (5 mm2) of a sterilized Kimwipes tissue was placed on the top of VS.
      Treatment 4 was identical to Treatment 3 except for the cryotube being filled
      with LN2. After each treatment, the cryotubes were capped and transferred to a
      LN2 tank. After warming, the recovered embryos were cultured in KSOM+AA for 1-3
      days. There were no differences in the recovery rate, overnight survival rate,
      blastocyst rate, and birth rate after embryo transfer among all treatment groups.
      Our results demonstrated an alternative simple, efficient, and mass reproducible
      method for vitrifying mouse embryos using papers as a vehicle and cryotubes as a
      container.

PMID- 23542663
TI  - Nerve conduction studies in the upper limb in the malwa region-normative data.
AB  - OBJECTIVE: To establish the normal electrophysiological data for the median and
      the ulnar nerves in normal healthy adults in the Malwa region of Punjab, India.
      METHODS: Nerve conduction studies were performed prospectively in the upper limbs
      of 100 carefully screened, healthy individuals of either sex, who were between
      the ages of 20 and 60 years, by using a standardized technique. RESULTS: Motor
      studies: The median distal latency (DL) in men was 3.4 (0.2) ms, the amplitude
      (CMAPA) was 10.80 (2.8) mV, the conduction velocity (MNCV) was 55.6 (2.5) m/s and
      the F-wave (min latency) was 27.57+/-2.54(21.5-34.2). In the ulnar nerve , the
      motor DL was 2.34 (0.25) ms, the amplitude (CMAPA) was 9.8(2.6) mV, MNCV was 63.4
      (3.0) m/s and the F-Wave(min latency) was 26.29+/-2.12(21.6-34.7). In the sensory
      studies, the median nerve DL was 2.0(0.35) ms, SNCV was 53.4+/-3.0 m/s and the
      amplitude (SNAPA)was 59.3 (16.4) MUV for men and it was 68.7(28.4) MUV for women.
      For the ulnar nerve in men, the DL was 1.85(0.25)ms, SNCV was 55.5 (4.1) m/s and
      the amplitude(SNAPA) was 55.5 (18.4) MUV for men and it was 64.9 (16.8) MUV for
      women. Only the gender showed a statistically significant effect on the sensory
      nerve action potential for the median (p < 0.04) and the ulnar nerves (p <
      0.041). CONCLUSION: The normative conduction parameters of the commonly tested
      nerves in the upper limb were established in our EMG lab. The mean motor nerve
      conduction parameters for the median and the ulnar nerves correlated favourably
      with the existing literature data. However, for the sensory nerves, a higher
      value for the nerve action potential amplitude was demonstrated in this study.

PMID- 23542664
TI  - Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25
      microdeletion.
AB  - A female patient, 20 years of age, is reported with a history characterized by
      developmental and psychomotor delay, and during grammar-school period increasing
      learning problems, ritualistic behaviours and social withdrawal. Subsequently,
      challenging and autistic-like behaviours became prominent. The patient showed
      mild facial dysmorphisms, long thin fingers with bilateral mild short V
      metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination
      disclosed obsessive, ritualistic behaviours and vague ideas of reference.
      Neuropsychological assessment demonstrated mild intellectual disability, mental
      inflexibility and incongruent affect. MRI-scanning of the brain showed no
      relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo
      interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be
      causative for the developmental delay, perseverative cognitive phenotype and
      dysmorphisms. To the authors knowledge, this is the first report of a de novo
      4q25 microdeletion that presents with a specific behavioural phenotype.

PMID- 23542665
TI  - Clinical characterization of DISP1 haploinsufficiency: A case report.
AB  - Chromosome 1q41q42 microdeletions have been classified as a syndrome consisting
      of significant developmental delay, seizures, and characteristic dysmorphic
      features. They harbor different breakpoints and their smallest region of overlap
      at 1q41q42 involves several genes, including DISP1. Deletion or variants of DISP1
      have been proposed as a candidate for the midline defects in this syndrome but
      may not be responsible for its major features in some cases. We report here a
      patient with a 183-kb deletion in chromosome 1q41, representing the smallest
      deletion identified among cases of the 1q41q42 microdeletion syndrome. The
      involved genes are DISP1 and TLR5. This patient developed seizures and
      developmental delay but showed no facial dysmorphism or organ defects. This
      deleted region was inherited from a phenotypically normal parent. This case may
      help define the role of the DISP1 haploinsufficiency in phenotype and support the
      suggestion that DISP1 mutation or deletion may reveal incomplete penetrance.

PMID- 23542666
TI  - Chromosome 20p inverted duplication deletion identified in a Thai female adult
      with mental retardation, obesity, chronic kidney disease and characteristic
      facial features.
AB  - We report on a 21-year-old Thai woman presenting with mental retardation,
      developmental delays, selective mutism, distinctive facial features,
      sensorineural hearing loss, single right kidney, uterine didelphys and obesity. A
      longitudinal clinical course beginning in childhood revealed excessive weight
      gain, poor language skills and poor school performance. Chronic kidney disease
      stage 4, with elevated blood pressure, was first noted in adulthood. Array
      comparative genomic hybridization detected a copy loss at 20p13 co-existing with
      a copy gain at 20p13-20p11.22. A conventional cytogenetic study revealed the
      complex structural rearrangement of chromosome 20 [der (20) dup (20) (p11.2p13)
      del (20) (p13.pter)]. A FISH analysis, using probes against duplication and
      deletion regions, confirmed that there was an inverted duplication of p11.2-p13
      and a deletion in the subtelomere region. Previous reports have identified this
      cytogenetic characterization in a Caucasian boy. Therefore, this is the first
      reported case of chromosome 20p inverted duplication deletion syndrome in an
      adult from the Southeast Asian population group.

PMID- 23542667
TI  - High incidence of Meniere-like symptoms in relatives of Meniere patients in the
      areas of Oulu University Hospital and Kainuu Central Hospital in Finland.
AB  - Objective of this study was to systematically investigate the family histories of
      a large set of patients affected with Meniere's disease to determine the
      prevalence of familial MD and Meniere-like symptoms in their families. All 640
      patients treated at the Oulu University Hospital and Kainuu Central Hospitals
      during 2005-2010 for Meniere's disease were selected as the initial study
      population. A postal family history survey was sent to all subjects. Hospital
      records of all patients were studied to confirm diagnosis and sufficient
      differential diagnosis. All patients that revealed a positive family history of
      Meniere's disease or Meniere-like symptoms were phone interviewed and the
      probability of Meniere's disease in a relative was estimated on a three level
      scale: probable, possible or unlikely. Affected family members of the patients
      were recruited to the study if possible. Familial Meniere's disease could be
      confirmed in 9.3% of patients, but 32.7% patients reported Meniere-like symptoms
      in their family. It was not possible to confirm all cases, but a family history
      of Meniere's disease was convincing (confirmed or probable) in 23.4% of the
      patients. Genetic factors are significant in the development of Meniere's
      disease.

PMID- 23542668
TI  - Poor socio-economic status in 47,XXX --an unexpected effect of an extra X
      chromosome.
AB  - One of the most common sex chromosomal abnormalities in females is 47,XXX
      syndrome, which is characterized by tall stature and reduced IQ, but with a
      variable phenotype. In order to elaborate on the characteristics of this
      syndrome, we undertook an investigation in all diagnosed 47,XXX females at risk
      in Denmark and compared their socio-economic status with an age-matched cohort of
      the female background population as well as with all Danes diagnosed with Turner
      syndrome. We focused on cohabitation, motherhoods, income, education, retirement
      and convictions. Furthermore, we investigated whether some of these parameters
      influenced the increased mortality identified previously. Thus, socio-economic
      data were retrieved in 108 47,XXX persons, 10,297 controls, and 831 with Turner
      syndrome. Comparing the 47,XXX persons with their controls, we identified
      significantly decreased numbers of first partnership, number of mothers, and
      number of persons with an education in 47,XXX persons. Significantly more 47,XXX
      persons retired. In the younger age groups an increased number had income below
      the median among controls. The increased mortality identified previously was not
      explained by the reduced number of partnerships or the reduced number of persons
      with an education. Comparing the 47,XXX persons with Turner syndrome persons, we
      identified increased number of first partnership, number of mothers, and reduced
      level of education. We hypothesize that the significantly decreased number of
      47,XXX persons becoming mothers could be due to hypogonadism in some. The
      affected socio-economic status suggests that the presence of an extra X
      chromosome has more detrimental effects than previously appreciated.

PMID- 23542669
TI  - Simultaneous determination of tramadol, O-desmethyltramadol and N
      desmethyltramadol in human urine by gas chromatography-mass spectrometry.
AB  - Analytical procedures for the determination of tramadol (T), O-desmethyltramadol
      (ODT), and N-desmethyltramadol (NDT) in human urine have been developed and
      validated using gas chromatography-mass spectrometry (GC/MS). Sample preparation
      involved liquid-liquid extraction with methyl-tert-butyl ether (MTBE) and
      followed by back extraction with 0.1 M hydrochloric acid. Proadifen (SKF525A) was
      selected as internal standard (IS). Extraction efficiencies of T, ODT and NDT
      were 102.12, 101.30, and 98.21%, respectively. The calibration curves were linear
      (r(2)>0.99) in the concentration range 10-1000 ng/mL for all compounds. Limits of
      quantification (LOQ) were 10, 10 and 20 ng/mL for T, ODT and NDT, respectively.
      Intra-assay precision was within 1.29-6.48% and inter-assay precision was within
      1.28-6.84% for T, ODT and NDT. Intra-assay accuracy was within 91.79-106.89% for
      all analytes. This method detected urine concentrations of T, ODT and NDT in six
      healthy volunteers for 7 days after administration of 50 mg oral doses of
      tramadol.

PMID- 23542670
TI  - Comparative pharmacokinetics of timosaponin B-II and timosaponin A-III after oral
      administration of Zhimu-Baihe herb-pair, Zhimu extract, free timosaponin B-II and
      free timosaponin A-III to rats.
AB  - The aim of this study was to compare the pharmacokinetics of timosaponin B-II and
      timosaponin A-III in rat plasma after oral administration of Zhimu-Baihe herb
      pair, Zhimu extract, free timosaponin B-II and free timosaponin A-III. After
      addition of internal standard (IS) ginsenoside Rh1, plasma samples were
      pretreated by protein precipitation. Chromatographic separation was carried out
      on a SHISEIDO CAPCELL PAK C18 column (100 mm * 3 mm i.d., 3.0 MUm) with the
      mobile phase consisting of acetonitrile and 0.05% (v/v) formic acid by linear
      gradient elution. The detection was performed on an Agilent G1946D single
      quadrupole mass spectrometer with negative electrospray ionization (ESI)
      interface in select-ion-monitoring (SIM) mode. The following ions: m/z 919 for
      timosaponin B-II, m/z 739 for timosaponin A-III and m/z 683 for the IS were used
      for quantitative determination. Good linearity was achieved over the
      concentration ranged from 4.0-793.3 ng/mL to 3.9-781.3 ng/mL for the two
      saponins. The precision of the in vivo study was evaluated by intra- and inter
      day assays and the percentages of relative standard deviation were all within
      15%. The plasma concentrations of timosaponin B-II and timosaponin A-III in rats
      at designated time periods were successfully determined using this fully
      validated method, and statistically significant differences (p<0.5) in
      pharmacokinetic parameters including AUC0-t, AUC0-infinity and MRT (mean
      residence time) were obtained. Compared to these pharmacokinetic parameters after
      oral administration of Zhimu extract and monomer solution, higher peak
      concentration (Cmax is higher), slower elimination (MRT is longer) and larger AUC
      values could be observed after giving Zhimu-Baihe herb-pair in our study.
      Therefore, this result not only elucidated the steady and long-lasting
      pharmacological properties but also revealed the practical value of the
      compatibility of herb-pair remedy.

PMID- 23542671
TI  - Comment on "specific binding of hydroxylated polychlorinated biphenyl metabolites
      and other substances to bovine calf uterine estrogen receptor: structure-binding
      relationships [Kramer and Giesy, Sci Total Environ 1999;233:141-61]".

PMID- 23542672
TI  - Sediment quality assessment in tidal salt marshes in northern California, USA: an
      evaluation of multiple lines of evidence approach.
AB  - The objective of this study was to evaluate the efficacy of integrating a
      traditional sediment quality triad approach with selected sublethal chronic
      indicators in resident species in assessing sediment quality in four salt marshes
      in northern California, USA. These included the highly contaminated (Stege Marsh)
      and relatively clean (China Camp) marshes in San Francisco Bay and two reference
      marshes in Tomales Bay. Toxicity potential of contaminants and benthic
      macroinvertebrate survey showed significant differences between contaminated and
      reference marshes. Sublethal responses (e.g., apoptotic DNA fragmentation, lipid
      accumulation, and glycogen depletion) in livers of longjaw mudsucker (Gillichthys
      mirabilis) and embryo abnormality in lined shore crab (Pachygrapsus crassipes)
      also clearly distinguished contaminated and reference marshes, while other
      responses (e.g., cytochrome P450, metallothionein) did not. This study
      demonstrates that additional chronic sublethal responses in resident species
      under field exposure conditions can be readily combined with sediment quality
      triads for an expanded multiple lines of evidence approach. This confirmatory
      step may be warranted in environments like salt marshes in which natural
      variables may affect interpretation of toxicity test data. Qualitative and
      quantitative integration of the portfolio of responses in resident species and
      traditional approach can support a more comprehensive and informative sediment
      quality assessment in salt marshes and possibly other habitat types as well.

PMID- 23542673
TI  - Small-scale variability in peatland pore-water biogeochemistry, Hudson Bay
      Lowland, Canada.
AB  - The Hudson Bay Lowland (HBL) of northern Ontario, Manitoba and Quebec, Canada is
      the second largest contiguous peatland complex in the world, currently containing
      more than half of Canada's soil carbon. Recent concerns about the ecohydrological
      impacts to these large northern peatlands resulting from climate change and
      resource extraction have catalyzed a resurgence in scientific research into this
      ecologically important region. However, the sheer size, heterogeneity and
      elaborate landscape arrangements of this ecosystem raise important questions
      concerning representative sampling of environmental media for chemical or
      physical characterization. To begin to quantify such variability, this study
      assessed the small-scale spatial (1m) and short temporal (21 day) variability of
      surface pore-water biogeochemistry (pH, dissolved organic carbon, and major ions)
      in a Sphagnum spp.-dominated, ombrotrophic raised bog, and a Carex spp.-dominated
      intermediate fen in the HBL. In general, pore-water pH and concentrations of
      dissolved solutes were similar to previously reported literature values from this
      region. However, systematic sampling revealed consistent statistically
      significant differences in pore-water chemistries between the bog and fen
      peatland types, and large within-site spatiotemporal variability. We found that
      microtopography in the bog was associated with consistent differences in most
      biogeochemical variables. Temporal changes in dissolved solute chemistry,
      particularly base cations (Na(+), Ca(2+) and Mg(2+)), were statistically
      significant in the intermediate fen, likely a result of a dynamic connection
      between surficial waters and mineral-rich deep groundwater. In both the bog and
      fen, concentrations of SO4(2-) showed considerable spatial variability, and a
      significant decrease in concentrations over the study period. The observed
      variability in peatland pore-water biogeochemistry over such small spatial and
      temporal scales suggests that under-sampling in northern peatland environments
      could lead to erroneous conclusions concerning the abundance and distribution of
      natural elements and pollutants alike.

PMID- 23542674
TI  - Transfer of metals and metalloids from soil to shoots in wild rosemary
      (Rosmarinus officinalis L.) growing on a former lead smelter site: human exposure
      risk.
AB  - This study aimed at estimating exposition risks to wild rosemary used as herbs in
      the contaminated area of the former smelting factory of L'Escalette (South of
      Marseille, France). Metals and metalloids i.e. Pb, As, Sb, Zn, and Cu
      concentrations were analyzed in soils and in rosemary aerial parts (stems and
      leaves) on two sites: one heavily contaminated and the other far away from the
      pollution source, considered as reference. The metal and metalloid transfer into
      water during the brewing process of herbal tea was also determined. A mixed
      contamination by the above-cited contaminants was demonstrated in soils of the
      factory site, with average concentrations of 9253, 1127, 309, 2698 and 32 mg/kg
      for Pb, As, Sb, Zn and Cu, respectively. However, metals and metalloids' transfer
      in rosemary aerial parts was limited, as bioaccumulation factors were under 1.
      Thus, Pb, As and Cu concentrations in leaves were below international regulation
      limits concerning ingestion of medicinal herbs (no regulation values available
      for Sb and Zn). This study highlighted that, if contaminated rosemary leaves were
      ingested, health risks may be limited since acceptable daily intake (ADI) for Pb,
      As, Sb and Cu (no ADI value available for Zn) will only be reached if very high
      quantities are consumed. Furthermore, we aimed to establish if this mixed
      contamination could alter rosemary's essential oil quality, and thereby the
      compositions of essential oils obtained from individuals on the heavily
      contaminated soil were compared to those obtained from the reference population.
      An increased biosynthesis of antioxidant compounds was favored in essential oils
      from rosemary individuals growing in contaminated site. Although the health risk
      of a long-term exposition of low level of the mixed contamination by rosemary
      ingestion is not easy to elucidate, the use of rosemary essential oils from
      contaminated site appears as safe.

PMID- 23542675
TI  - The interactive responses of water quality and hydrology to changes in multiple
      stressors, and implications for the long-term effective management of phosphorus.
AB  - Soluble reactive phosphorus (SRP) plays a key role in eutrophication, a global
      problem decreasing habitat quality and in-stream biodiversity. Mitigation
      strategies are required to prevent SRP fluxes from exceeding critical levels, and
      must be robust in the face of potential changes in climate, land use and a myriad
      of other influences. To establish the longevity of these strategies it is
      therefore crucial to consider the sensitivity of catchments to multiple future
      stressors. This study evaluates how the water quality and hydrology of a major
      river system in the UK (the River Thames) respond to alterations in climate, land
      use and water resource allocations, and investigates how these changes impact the
      relative performance of management strategies over an 80-year period. In the
      River Thames, the relative contributions of SRP from diffuse and point sources
      vary seasonally. Diffuse sources of SRP from agriculture dominate during periods
      of high runoff, and point sources during low flow periods. SRP concentrations
      rose under any future scenario which either increased a) surface runoff or b) the
      area of cultivated land. Under these conditions, SRP was sourced from
      agriculture, and the most effective single mitigation measures were those which
      addressed diffuse SRP sources. Conversely, where future scenarios reduced flow
      e.g. during winters of reservoir construction, the significance of point source
      inputs increased, and mitigation measures addressing these issues became more
      effective. In catchments with multiple point and diffuse sources of SRP, an all
      encompassing effective mitigation approach is difficult to achieve with a single
      strategy. In order to attain maximum efficiency, multiple strategies might
      therefore be employed at different times and locations, to target the variable
      nature of dominant SRP sources and pathways.

PMID- 23542676
TI  - Effects of Poisson noise in a IF model with STDP and spontaneous replay of
      periodic spatiotemporal patterns, in absence of cue stimulation.
AB  - We consider a network of leaky integrate and fire neurons, whose learning
      mechanism is based on the Spike-Timing-Dependent Plasticity. The spontaneous
      temporal dynamic of the system is studied, including its storage and replay
      properties, when a Poissonian noise is added to the post-synaptic potential of
      the units. The temporal patterns stored in the network are periodic
      spatiotemporal patterns of spikes. We observe that, even in absence of a cue
      stimulation, the spontaneous dynamics induced by the noise is a sort of
      intermittent replay of the patterns stored in the connectivity and a phase
      transition between a replay and non-replay regime exists at a critical value of
      the spiking threshold. We characterize this transition by measuring the order
      parameter and its fluctuations.

PMID- 23542677
TI  - Isolation of alpha-arbutin from Xanthomonas CGMCC 1243 fermentation broth by
      macroporous resin adsorption chromatography.
AB  - alpha-Arbutin is a glycosylated hydroquinone which has inhibitory function
      against tyrosinase. In this work, a one-step isolation of alpha-arbutin from
      Xanthomonas CGMCC 1243 fermentation broth by macroporous resin adsorption
      chromatography was investigated. The research results indicated that S-8 resin
      offered the best adsorption and desorption capacities for alpha-arbutin than
      others and its equilibrium adsorption data were well-fitted to the Freundlich
      isotherm. In order to optimize the operating parameters for separating alpha
      arbutin, dynamic adsorption and desorption tests on S-8 column chromatography
      were carried out. Under optimized conditions (adsorption volume of 7 bed volume
      (BV), mobile phase of 25% (v/v) ethanol solution and elution volume of 3 BV), the
      purity and recovery of alpha-arbutin were 97.3% (w/w) and 90.9% (w/w),
      respectively. The product was identified as alpha-arbutin by (13)C NMR and (1)H
      NMR analysis. Moreover, we scaled up S-8 column from laboratory test (10 cm * 2
      cm ID) to large scale (500 cm * 100 cm ID) without diminishing alpha-arbutin
      yield. In conclusion, the results in this work provide a one-step and cost
      effective method for large-scale production of alpha-arbutin.

PMID- 23542678
TI  - Association between serum levels of 25-hydroxyvitamin D and osteoarthritis: a
      systematic review.
AB  - OBJECTIVE: To systematically review the evidence for association between serum 25
      hydroxyvitamin D (25-(OH)D) and OA and the effect of vitamin D therapy on OA.
      METHODS: An English Medline, EMBASE and Cochrane Library search for vitamin D and
      OA from January 1980 to June 2012 was performed. Randomized controlled trials
      (RCTs), cohort, case-control and cross-sectional studies in adults were included.
      The methodological quality of the selected studies was assessed and a best
      evidence synthesis was used to summarize the results due to the heterogeneity of
      the studies. RESULTS: Of the 86 evaluated articles, 2 RCTs and 13 observational
      studies were included in the final analyses. The number of participants ranged
      from 64 to 1644 (0-100% women). The RCTs were only reported in abstract form and
      showed inconsistent results, most likely due to variations in their study design.
      There was insufficient or limited evidence for associations between 25-(OH)D and
      hand or hip OA. For knee radiographic OA as assessed by the Kellgren and Lawrence
      (KL) score, there was moderate evidence showing that low levels of 25-(OH)D were
      associated with increased progression of radiographic OA. Strong evidence for an
      association between 25-(OH)D and cartilage loss was apparent when joint space
      narrowing and changes in cartilage volume were considered collectively as
      cartilage loss. CONCLUSION: 25-(OH)D appears to be implicated in structural
      changes of knee OA rather than symptoms, and further well-designed RCTs are
      required to determine whether vitamin D supplementation can slow disease
      progression. There is insufficient evidence for other sites.

PMID- 23542679
TI  - A visual assay to monitor T6SS-mediated bacterial competition.
AB  - Type VI secretion systems (T6SSs) are molecular nanomachines allowing Gram
      negative bacteria to transport and inject proteins into a wide variety of target
      cells(1,2). The T6SS is composed of 13 core components and displays structural
      similarities with the tail-tube of bacteriophages(3). The phage uses a tube and a
      puncturing device to penetrate the cell envelope of target bacteria and inject
      DNA. It is proposed that the T6SS is an inverted bacteriophage device creating a
      specific path in the bacterial cell envelope to drive effectors and toxins to the
      surface. The process could be taken further and the T6SS device could perforate
      other cells with which the bacterium is in contact, thus injecting the effectors
      into these targets. The tail tube and puncturing device parts of the T6SS are
      made with Hcp and VgrG proteins, respectively(4,5). The versatility of the T6SS
      has been demonstrated through studies using various bacterial pathogens. The
      Vibrio cholerae T6SS can remodel the cytoskeleton of eukaryotic host cells by
      injecting an "evolved" VgrG carrying a C-terminal actin cross-linking
      domain(6,7). Another striking example was recently documented using Pseudomonas
      aeruginosa which is able to target and kill bacteria in a T6SS-dependent manner,
      therefore promoting the establishment of bacteria in specific microbial niches
      and competitive environment(8,9,10). In the latter case, three T6SS-secreted
      proteins, namely Tse1, Tse2 and Tse3 have been identified as the toxins injected
      in the target bacteria (Figure 1). The donor cell is protected from the
      deleterious effect of these effectors via an anti-toxin mechanism, mediated by
      the Tsi1, Tsi2 and Tsi3 immunity proteins(8,9,10). This antimicrobial activity
      can be monitored when T6SS-proficient bacteria are co-cultivated on solid
      surfaces in competition with other bacterial species or with T6SS-inactive
      bacteria of the same species(8,11,12,13). The data available emphasized a
      numerical approach to the bacterial competition assay, including time-consuming
      CFU counting that depends greatly on antibiotic makers. In the case of antibiotic
      resistant strains like P. aeruginosa, these methods can be inappropriate.
      Moreover, with the identification of about 200 different T6SS loci in more than
      100 bacterial genomes(14), a convenient screening tool is highly desirable. We
      developed an assay that is easy to use and requires standard laboratory material
      and reagents. The method offers a rapid and qualitative technique to monitor the
      T6SS-dependent bactericidal/bacteriostasis activity by using a reporter strain as
      a prey (in this case Escherichia coli DH5alpha) allowing a-complementation of the
      lacZ gene. Overall, this method is graphic and allows rapid identification of
      T6SS-related phenotypes on agar plates. This experimental protocol may be adapted
      to other strains or bacterial species taking into account specific conditions
      such as growth media, temperature or time of contact.

PMID- 23542680
TI  - Dronedarone and Captisol-enabled amiodarone in an experimental cardiac arrest.
AB  - OBJECTIVE: To compare the energy required for defibrillation and postshock
      outcomes after the administration of dronedarone, amiodarone, and placebo in a
      porcine model of cardiac arrest. METHODS: Forty-two pigs were randomized to
      amiodarone, dronedarone, or control treatments. After induction of ventricular
      fibrillation, compressions and ventilations were performed for 3 minutes and
      treatment was administered over 30 seconds. If defibrillation was unsuccessful,
      cardiopulmonary resuscitation continued and repeated shocks were administered
      every 2 minutes with continual hemodynamic monitoring for a total duration of 30
      minutes. RESULTS: The cumulative energy required for defibrillation was 570 +/-
      422 J for dronedarone, 441 +/- 365 J for amiodarone, and 347 +/- 281 J for
      control (P = not significant). Survival at 30 minutes was 1 (7.1%) for
      dronedarone compared with 11 (78.6%) for control (P = 0.001). Mortality in the
      dronedarone group was because of refibrillation in 3 (21.4%) cases,
      atrioventricular block in 1 (7.1%) case, and hypotension not because of
      bradycardia in 9 (64.3%) cases. Two minutes after successful defibrillation,
      systolic aortic pressure was lower in dronedarone versus control (86.6 +/- 26.9
      vs. 110 +/- 15.1 mm Hg; P = 0.035). CONCLUSIONS: The administration of
      dronedarone resulted in a significant reduction in survival and both systolic
      aortic and coronary perfusion pressure compared with control.

PMID- 23542682
TI  - Dietary and sociodemographic determinants of bisphenol A urine concentrations in
      pregnant women and children.
AB  - Bisphenol A (BPA) exposure during early life may have endocrine-disrupting
      effects, but the dietary and sociodemographic predictors of BPA exposure during
      pregnancy and childhood remain unclear. Our aim was to evaluate the correlations
      between, and sociodemographic and dietary predictors of, serial urinary BPA
      concentrations measured during pregnancy and childhood in a Spanish birth cohort
      study. BPA was measured in two spot urine samples collected from 479 women during
      the first and third trimester of pregnancy and in one urine sample from their 4
      year old children (n=130). Average dietary intakes were reported in food
      frequency questionnaires during the first and third pregnancy trimester and at
      age 4years. Multivariate mixed models and linear regression models were used to
      estimate associations between sociodemographic and dietary factors and BPA
      concentrations. A small, but statistically significant correlation was found
      between serial maternal BPA concentrations measured during pregnancy (r=0.17).
      Pregnant women who were younger, less-educated, smoked, and who were exposed to
      second-hand tobacco smoke (SHS) had higher BPA concentrations than others. BPA
      concentrations were also higher in children exposed to SHS. High consumption of
      canned fish during pregnancy was associated with 21% [GM ratio=1.21; 95%CI 1.02,
      1.44] and 25% [GM ratio=1.25; 95%CI 1.05, 1.49] higher urinary BPA concentrations
      in the first and third pregnancy trimester, respectively, compared to the lowest
      consumption group. This study suggests that canned fish may be a major source of
      BPA during pregnancy in Spain, a country of high canned fish consumption. Further
      evaluation of specific BPA exposure sources in the sociodemographic group of
      younger women who smoke, are exposed to SHS, and have a low educational level is
      needed. Studies identifying sources of exposure would benefit from repeat BPA
      measurements and questionnaires specifically focused on dietary and packaging
      sources.

PMID- 23542681
TI  - Age-relevant renal effects of cadmium exposure through consumption of home
      harvested rice in female Japanese farmers.
AB  - There are cadmium-polluted areas in Japan, where farmers may be at risk of renal
      dysfunction due to cadmium exposure through consumption of home-harvested rice.
      The aims of this study were to investigate levels of cadmium exposure and
      accumulation and their renal effects in female farmers residing in cadmium
      polluted areas, and to consider the relevance of age to the effects of cadmium.
      We conducted a cross-sectional study of 1200 women (40-79years old) without
      symptomatic disorders in two cadmium-polluted areas and one unpolluted area as a
      control. Rice, blood, and urine samples were collected to measure the cadmium
      levels, together with urinary levels of alpha1-microglobulin and beta2
      microglobulin for renal tubular function. Cadmium levels in rice were
      significantly higher in the polluted areas than control area. Blood and urinary
      cadmium levels, along with urinary protein levels, were also significantly higher
      in the polluted areas, especially among the elder subjects. There was one case of
      cadmium nephropathy in the polluted areas. Age- and urinary cadmium-specific
      analysis for all the subjects showed a mild linear dose-response relationship
      between urinary cadmium and proteins in the younger women, and a steep progress
      of renal dysfunction over the threshold of urinary cadmium (10MUg/g creatinine)
      in the older women. In conclusion, the aged women in the polluted areas showed
      high accumulation of cadmium and deterioration of renal function through
      consumption of rice. Also, the aging process itself appeared to contribute to the
      different renal effects of cadmium observed in the elderly population.

PMID- 23542683
TI  - Notch3 induces epithelial-mesenchymal transition and attenuates carboplatin
      induced apoptosis in ovarian cancer cells.
AB  - OBJECTIVE: Notch3 is implicated in chemoresistance of ovarian cancer, yet the
      molecular mechanism underlying Notch3-mediated drug resistance remains to be
      elucidated. Here, we investigated the role of Notch3 in carboplatin-induced
      apoptosis in ovarian cancer cells. METHODS: Ovarian cancer cell line OVCA429
      cells were stably transduced with an empty vector or a retroviral vector
      expressing the Notch3 intracellular domain (NICD3, the constitutively active form
      of Notch3) to generate OVCA429/vector and OVCA429/NICD3 cells. Epithelial
      mesenchymal transition (EMT) was determined by morphological change and
      expression of the EMT markers. Carboplatin-induced cytotoxicity was determined by
      the neutral red uptake assay. Apoptosis was determined by Annexin V staining and
      Western blotting. Carboplatin-induced phosphorylation of extracellular signal
      regulated kinase (ERK) was identified by a phospho-kinase array and confirmed by
      Western blotting. RESULTS: Activation of Notch3 in OVCA429 cells causes a spindle
      and fibroblast-like morphology, induces the expression of smooth muscle alpha
      actin, Slug and Snail, but decreases the expression of E-cadherin, indicating
      that Notch3 activation induces EMT in OVCA429 cells. Furthermore, Notch3
      activation renders OVCA429 cells more resistant to carboplatin-induced
      cytotoxicity and attenuates carboplatin-induced apoptosis in these cells. Our
      results indicate that phosphorylation of ERK is a positive regulator of
      carboplatin-induced apoptosis in OVCA429 cells. Interestingly, carboplatin
      induced ERK phosphorylation is inhibited by Notch3 activation. CONCLUSIONS:
      Notch3 activation induces EMT and attenuates carboplatin-induced apoptosis in
      OVCA429 cells. ERK phosphorylation plays a pro-apoptotic role in carboplatin
      induced apoptosis in OVCA429 cells. Interestingly, Notch3 activation attenuates
      carboplatin-induced ERK phosphorylation in these cells.

PMID- 23542684
TI  - Outpatient end of life discussions shorten hospital admissions in gynecologic
      oncology patients.
AB  - OBJECTIVE: The study goal was to determine whether prior outpatient exposure to
      hospice discussion altered the inpatient course and end-of-life (EOL) care among
      patients ultimately discharged to hospice. METHODS: Medical records from January
      2009 to June 2012 were reviewed and data were abstracted under an IRB-approved
      protocol. Hospice discussions were identified in the last outpatient clinical
      encounter prior to admission. Kaplan-Meier was used to estimate overall survival
      (OS) and the log-rank test was used to test for differences. RESULTS: There were
      89 hospitalizations resulting in discharge to hospice care: 41 women with ovarian
      (46%), 23 with uterine (29%), 19 with cervical (21.3%), and with 6 vulvar/vaginal
      (6.7%) cancers. 83 patients (93%) had outpatient clinical encounters prior to
      admission;18% (15/83) were exposed to a hospice discussion (HD) and 82% (68/83)
      were not (NHD). Median time from last outpatient encounter was 18 days (range 0
      371). NHD patients had longer inpatient length of stay (median 7 days vs. 4 days,
      p=0.008) and were less likely to receive palliative care consults than the HD
      patients (65% vs. 93%, p=0.03). Median OS for HD patients was 33 days (95% CI 22d
      61 d) vs. 60 days (95% CI 49 d-84 d) for NHD patients (p=0.01). There were no
      differences detected based on race, ethnicity, or insurance status. CONCLUSIONS:
      HD patients had significantly shorter OS suggesting that providers were accurate
      in identifying patients nearing the EOL. Patients exposed to outpatient hospice
      discussions had a shorter length of stay and increased utilization of palliative
      care resources.

PMID- 23542685
TI  - Goblet cell compound exocytosis in the defense against bacterial invasion in the
      colon exposed to ischemia-reperfusion.
AB  - In recent years, the importance of the mucus layer in the colon has become
      increasingly clear. Disturbance of the mucus layer has been implicated in a
      variety of intestinal diseases. We have recently investigated the importance of
      the mucus layer in colon ischemia-reperfusion (IR). Using a newly developed human
      and rat colon IR model, we showed that colon ischemia leads to mucus barrier
      breakdown. This allowed intraluminal bacteria to interact with the colonic
      epithelium, which was associated with an inflammatory response. Intriguingly, we
      found goblet cells to respond immediately by expelling their mucin granules into
      the gut lumen, which flushed bacteria from the colonic crypts and resulted in
      rapid restoration of the mucus layer during reperfusion. Our study might explain
      why ischemic colitis tends to have favorable outcomes and can often be treated
      conservatively.

PMID- 23542686
TI  - Hand grip strength and 2-minute walk test in chronic graft-versus-host disease
      assessment: analysis from the Chronic GVHD Consortium.
AB  - Hand grip strength (HGS) and the 2-minute walk test (2MWT) have been proposed as
      elements of chronic graft-versus-host disease (GVHD) assessment in clinical
      trials. Using all available data (n = 584 enrollment visits, 1689 follow-up
      visits, total of 2273 visits) from a prospective observational cohort study, we
      explored the relationship between HGS and 2MWT and patient-reported measures (Lee
      symptom scale, MOS 36-Item Short-Form Health Survey [SF-36], and Functional
      Assessment of Cancer Therapy [FACT]-Bone Marrow Transplantation quality of life
      instruments and Human Activity Profile [HAP]), chronic GVHD global severity
      (National Institutes of Health global score, clinician global score, and patient
      reported global score), calculated and clinician-reported chronic GVHD response,
      and mortality (overall survival, nonrelapse mortality, and failure-free survival)
      in multivariable analyses adjusted for significant covariates. 2MWT was
      significantly associated with intuitive domains of the Lee Symptom Scale
      (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and
      domain scores, and HAP scores (all P < .001). Fewer associations were detected
      with the HGS. The 2MWT and HGS both had significant association with global
      chronic GVHD severity. In multivariable analysis, 2MWT was significantly
      associated with overall survival, nonrelapse mortality, and failure-free
      survival, whereas no association was found for HGS. 2MWT and HGS were not
      sensitive to National Institutes of Health or clinician-reported response. Based
      on independent association with mortality, these data support the importance of
      the 2MWT for identification of high-risk chronic GVHD patients. However, change
      in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in
      clinical trials.

PMID- 23542687
TI  - Serial measurement of WT1 expression and decrement ratio until hematopoietic cell
      transplantation as a marker of residual disease in patients with cytogenetically
      normal acute myelogenous leukemia.
AB  - Using real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1)
      expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in
      adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML)
      and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104
      patients. Data collected after induction chemotherapy were available for all
      patients, but only 68 patients were treated with HSCT. Significant WT1 expression
      cut-offs were determined by receiver operation characteristic curve analysis, and
      rates of overall survival (OS) and disease-free survival (DFS) were estimated.
      WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT
      compared with the diagnostic level were calculated. Higher WT1 expression at
      diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015,
      <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were
      determined at the median for diagnostic WT1 expression and at the 25% level from
      the top for other time points excluding post-HSCT. The WT1 DR >= 1-log after
      induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR
      >= 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003).
      Results of WT1 DR were consistently applicable in each subgroup with higher (>=
      1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3
      ITD-negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT
      more accurately than did the diagnostic WT1 expression. WT1 expression may serve
      as a reliable marker for residual disease and WT1 DR as a prognostic indicator,
      particularly in NPM1-wild-type/FLT3-ITD-negative CN-AML. These measures may be
      applied throughout the course of treatment and even after HSCT.

PMID- 23542688
TI  - Live imaging of astrocyte responses to acute injury reveals selective
      juxtavascular proliferation.
AB  - Astrocytes are thought to have important roles after brain injury, but their
      behavior has largely been inferred from postmortem analysis. To examine the
      mechanisms that recruit astrocytes to sites of injury, we used in vivo two-photon
      laser-scanning microscopy to follow the response of GFP-labeled astrocytes in the
      adult mouse cerebral cortex over several weeks after acute injury. Live imaging
      revealed a marked heterogeneity in the reaction of individual astrocytes, with
      one subset retaining their initial morphology, another directing their processes
      toward the lesion, and a distinct subset located at juxtavascular sites
      proliferating. Although no astrocytes actively migrated toward the injury site,
      selective proliferation of juxtavascular astrocytes was observed after the
      introduction of a lesion and was still the case, even though the extent was
      reduced, after astrocyte-specific deletion of the RhoGTPase Cdc42. Thus,
      astrocyte recruitment after injury relies solely on proliferation in a specific
      niche.

PMID- 23542689
TI  - Degeneration and impaired regeneration of gray matter oligodendrocytes in
      amyotrophic lateral sclerosis.
AB  - Oligodendrocytes associate with axons to establish myelin and provide metabolic
      support to neurons. In the spinal cord of amyotrophic lateral sclerosis (ALS)
      mice, oligodendrocytes downregulate transporters that transfer glycolytic
      substrates to neurons and oligodendrocyte progenitors (NG2(+) cells) exhibit
      enhanced proliferation and differentiation, although the cause of these changes
      in oligodendroglia is unknown. We found extensive degeneration of gray matter
      oligodendrocytes in the spinal cord of SOD1 (G93A) ALS mice prior to disease
      onset. Although new oligodendrocytes were formed, they failed to mature,
      resulting in progressive demyelination. Oligodendrocyte dysfunction was also
      prevalent in human ALS, as gray matter demyelination and reactive changes in
      NG2(+) cells were observed in motor cortex and spinal cord of ALS patients.
      Selective removal of mutant SOD1 from oligodendroglia substantially delayed
      disease onset and prolonged survival in ALS mice, suggesting that ALS-linked
      genes enhance the vulnerability of motor neurons and accelerate disease by
      directly impairing the function of oligodendrocytes.

PMID- 23542690
TI  - Strengthening the accumbal indirect pathway promotes resilience to compulsive
      cocaine use.
AB  - A hallmark of addiction is the loss of control over drug intake, which is seen in
      only a fraction of those exposed to stimulant drugs such as cocaine. The cellular
      mechanisms underlying vulnerability or resistance to compulsive drug use remain
      unknown. We found that individual variability in the development of highly
      motivated and perseverative behavior toward cocaine is associated with synaptic
      plasticity in medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) in
      the nucleus accumbens (NAc) of mice. Potentiation of glutamatergic inputs onto
      indirect pathway D2-MSNs was associated with resilience toward compulsive cocaine
      seeking. Inhibition of D2-MSNs using a chemicogenetic approach enhanced the
      motivation to obtain cocaine, whereas optogenetic activation of D2-MSNs
      suppressed cocaine self-administration. These results indicate that recruitment
      of D2-MSNs in NAc functions to restrain cocaine self-administration and serves as
      a natural protective mechanism in drug-exposed individuals.

PMID- 23542692
TI  - Taste-independent nutrient selection is mediated by a brain-specific Na+ /solute
      co-transporter in Drosophila.
AB  - Animals can determine the nutritional value of sugar without the influence of
      taste. We examined a Drosophila mutant that is insensitive to the nutritional
      value of sugars, responding only to the concentration (that is, sweetness). The
      affected gene encodes a sodium/solute co-transporter-like protein, designated
      SLC5A11 (or cupcake), which is structurally similar to mammalian sodium/glucose
      co-transporters that transport sugar across the intestinal and renal lumen.
      However, SLC5A11 was prominently expressed in 10-13 pairs of R4 neurons of the
      ellipsoid body in the brain and functioned in these neurons for selecting
      appropriate foods.

PMID- 23542691
TI  - FIP200 is required for maintenance and differentiation of postnatal neural stem
      cells.
AB  - Despite recent studies showing that inhibition of autophagy depletes the
      hematopoietic stem cell pool and increases intracellular reactive oxygen species
      (ROS), it remains unknown whether autophagy is essential in the maintenance of
      other stem cells. Moreover, it is unclear whether and how the aberrant ROS
      increase causes depletion of stem cells. Here we report that ablation of FIP200
      (also known as Rb1cc1), a gene essential for autophagy induction in mammalian
      cells, results in a progressive loss of neural stem cells (NSCs) and impairment
      in neuronal differentiation specifically in the postnatal brain, but not the
      embryonic brain, in mice. The defect in maintaining the postnatal NSC pool was
      caused by p53-dependent apoptotic responses and cell cycle arrest. However, the
      impaired neuronal differentiation was rescued by treatment with the antioxidant N
      acetylcysteine but not by p53 inactivation. These data reveal that FIP200
      mediated autophagy contributes to the maintenance and functions of NSCs through
      regulation of oxidative state.

PMID- 23542693
TI  - Antibacterial performance of nanoscaled visible-light responsive platinum
      containing titania photocatalyst in vitro and in vivo.
AB  - BACKGROUND: Traditional antibacterial photocatalysts are primarily induced by
      ultraviolet light to elicit antibacterial reactive oxygen species. New generation
      visible-light responsive photocatalysts were discovered, offering greater
      opportunity to use photocatalysts as disinfectants in our living environment.
      Recently, we found that visible-light responsive platinum-containing titania
      (TiO2-Pt) exerted high performance antibacterial property against soil-borne
      pathogens even in soil highly contaminated water. However, its physical and
      photocatalytic properties, and the application in vivo have not been well
      characterized. METHODS: Transmission electron microscopy, energy dispersive
      spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, ultraviolet
      visible absorption spectrum and the removal rate of nitrogen oxides were
      therefore analyzed. The antibacterial performance under in vitro and in vivo
      conditions was evaluated. RESULTS: The apparent quantum efficiency for visible
      light illuminated TiO2-Pt is relatively higher than several other titania
      photocatalysts. The killing effect achieved approximately 2 log reductions of
      pathogenic bacteria in vitro. Illumination of injected TiO2-Pt successfully
      ameliorated the subcutaneous infection in mice. CONCLUSIONS: This is the first
      demonstration of in vivo antibacterial use of TiO2-Pt nanoparticles. When
      compared to nanoparticles of some other visible-light responsive photocatalysts,
      TiO2-Pt nanoparticles induced less adverse effects such as exacerbated platelet
      clearance and hepatic cytotoxicity in vivo. GENERAL SIGNIFICANCE: These findings
      suggest that the TiO2-Pt may have potential application on the development of an
      antibacterial material in both in vitro and in vivo settings.

PMID- 23542695
TI  - Biochemical indicator of sickle cell disease: preliminary report from India.
AB  - Blood biochemistry has significant effect on pathophysiology of human body.
      Recently few studies found the association of biochemical abnormalities in sickle
      cell patients. Sickle cell disease showed clinical variability where African
      ancestors have severe phenotype than Indian sicklers. Our aim was to evaluate the
      biochemicals in sickle cell patients and their effect on severity. Here we
      present the comparative biochemical levels in sickle cell patients as well as
      controls. Sickle cell patients diagnosed by HPLC and biochemical analysis done by
      Beckman-auto analyzer. T test applied for statistical analysis. Result showed the
      renal abnormality lesser in patients and related biochemical within the normal
      range and statistically not significant. Electrolytes, hepatic enzymes, alkaline
      phosphatase and glucose were elevated and statistically significant (P value
      <0.05). Observation of the study concludes the biochemical abnormality play a
      significant role in sickle cell patient's physiopathology and can be used to
      management of the disease.

PMID- 23542694
TI  - MicroRNA-382 expression is elevated in the olfactory neuroepithelium of
      schizophrenia patients.
AB  - Schizophrenia is a common neuropsychiatric disorder that has a strong genetic
      component. MicroRNAs (miRNAs) have been implicated in neurodevelopmental and
      psychiatric disorders including schizophrenia, as indicated by their
      dysregulation in post-mortem brain tissues and in peripheral blood of
      schizophrenia patients. The olfactory epithelium (OE) is one of the few
      accessible neural tissues that contain neurons and their stem cells. Previous
      studies showed that OE-derived tissues and cells can be safely and easily
      collected from live human subjects and may provide a "window" into neuronal
      processes involved in disorders such as schizophrenia, while avoiding the
      limitations of using postmortem brain samples or non-neuronal tissues. In this
      study, we found that the brain-enriched miR-382 (miR-382-5p) expression was
      elevated in in vitro cultured olfactory cells, in a cohort of seven schizophrenia
      patients compared with seven non-schizophrenic controls. MiR-382 elevation was
      further confirmed in laser-capture microdissected OE neuronal tissue (LCM-OE),
      enriched for mature olfactory neurons, in a cohort of 18 schizophrenia patients
      and 18 non-schizophrenic controls. In sharp contrast, miR-382 expression could
      not be detected in lymphoblastoid cell lines generated from schizophrenic or non
      schizophrenic individuals. We further found that miR-382 directly regulates the
      expression of two genes, FGFR1 and SPRY4, which are downregulated in both the
      cultured olfactory cells and LCM-OE derived from schizophrenia patients. These
      genes are involved in the fibroblast growth factor (FGF) signaling pathway, while
      impairment of this pathway may underlie abnormal brain development and function
      associated with schizophrenia. Our data suggest that miR-382 elevation detected
      in patients' OE-derived samples might serve to strengthen current biomarker
      studies in schizophrenia. This study also illustrates the potential utility of OE
      derived tissues and cells as surrogate samples for the brain.

PMID- 23542696
TI  - Comparison of intraocular pressure measurements and assessment of intraobserver
      and interobserver reproducibility with the portable ICare rebound tonometer and
      Goldmann applanation tonometer in glaucoma patients.
AB  - PURPOSE: The goals of our study were to analyze the correlation of rebound
      tonometer (RBT) and Goldmann applanation tonometer (GAT), assess the
      intraobserver and interobserver reproducibility of these tonometers, and
      investigate the influence of central corneal thickness (CCT) on intraocular
      pressure (IOP) measurements recorded with both tonometers in glaucoma patients
      under treatment. METHODS: In a prospective study of 65 eyes with glaucoma, IOP
      was measured using RBT and GAT, followed by measurements of CCT. RESULTS: A clear
      correlation between RBT and GAT was found (r=0.89, P<0.001). Bland-Altman
      analysis showed a mean difference of measurements by GAT and RBT of 2.45 mm Hg
      with 2 SD=4.24 mm Hg. Both tonometers were affected by CCT. High intraobserver
      correlation coefficients were found with both tonometers (0.981 and 0.979 for RBT
      for examiner 1 and examiner 2, respectively, and 0.989 for GAT for both
      examiners). Interobserver agreement appeared to be better with GAT when compared
      with RBT (variation coefficients were 4.6% for GAT and 7.1% for RBT).
      CONCLUSIONS: RBT may have a potential role and use in routine evaluation and
      management of glaucoma patients given its high correlation with GAT and high
      reproducibility in IOP measurements. As with GAT, measurements obtained with RBT
      are affected by CCT, reinforcing the role of pachymetry in glaucoma management.

PMID- 23542697
TI  - Mutations in DEPDC5 cause familial focal epilepsy with variable foci.
AB  - The majority of epilepsies are focal in origin, with seizures emanating from one
      brain region. Although focal epilepsies often arise from structural brain
      lesions, many affected individuals have normal brain imaging. The etiology is
      unknown in the majority of individuals, although genetic factors are increasingly
      recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF)
      is notable because family members have seizures originating from different
      cortical regions. Using exome sequencing, we detected DEPDC5 mutations in two
      affected families. We subsequently identified mutations in five of six additional
      published large families with FFEVF. Study of families with focal epilepsy that
      were too small for conventional clinical diagnosis with FFEVF identified DEPDC5
      mutations in approximately 12% of families (10/82). This high frequency
      establishes DEPDC5 mutations as a common cause of familial focal epilepsies.
      Shared homology with G protein signaling molecules and localization in human
      neurons suggest a role of DEPDC5 in neuronal signal transduction.

PMID- 23542698
TI  - Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome.
AB  - Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome
      (HUS) features episodes of small-vessel thrombosis resulting in microangiopathic
      hemolytic anemia, thrombocytopenia and renal failure. Atypical HUS (aHUS) can
      result from genetic or autoimmune factors that lead to pathologic complement
      cascade activation. Using exome sequencing, we identified recessive mutations in
      DGKE (encoding diacylglycerol kinase E) that co-segregated with aHUS in nine
      unrelated kindreds, defining a distinctive Mendelian disease. Affected
      individuals present with aHUS before age 1 year, have persistent hypertension,
      hematuria and proteinuria (sometimes in the nephrotic range), and develop chronic
      kidney disease with age. DGKE is found in endothelium, platelets and podocytes.
      Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C
      (PKC), which promotes thrombosis, and DGKE normally inactivates DAG signaling. We
      infer that loss of DGKE function results in a prothrombotic state. These findings
      identify a new mechanism of pathologic thrombosis and kidney failure and have
      immediate implications for treating individuals with aHUS.

PMID- 23542699
TI  - Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly
      capillary malformation syndrome.
AB  - Microcephaly-capillary malformation (MIC-CAP) syndrome is characterized by severe
      microcephaly with progressive cortical atrophy, intractable epilepsy, profound
      developmental delay and multiple small capillary malformations on the skin. We
      used whole-exome sequencing of five patients with MIC-CAP syndrome and identified
      recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB)
      isopeptidase STAMBP (STAM-binding protein, also known as AMSH, associated
      molecule with the SH3 domain of STAM) that has a key role in cell surface
      receptor-mediated endocytosis and sorting. Patient cell lines showed reduced
      STAMBP expression associated with accumulation of ubiquitin-conjugated protein
      aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and
      PI3K-AKT-mTOR pathways. The latter cellular phenotype is notable considering the
      established connection between these pathways and their association with vascular
      and capillary malformations. Furthermore, our findings of a congenital human
      disorder caused by a defective DUB protein that functions in endocytosis
      implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors
      potentially influencing the progressive neuronal loss underlying MIC-CAP
      syndrome.

PMID- 23542700
TI  - The genome of the platyfish, Xiphophorus maculatus, provides insights into
      evolutionary adaptation and several complex traits.
AB  - Several attributes intuitively considered to be typical mammalian features, such
      as complex behavior, live birth and malignant disease such as cancer, also
      appeared several times independently in lower vertebrates. The genetic mechanisms
      underlying the evolution of these elaborate traits are poorly understood. The
      platyfish, X. maculatus, offers a unique model to better understand the molecular
      biology of such traits. We report here the sequencing of the platyfish genome.
      Integrating genome assembly with extensive genetic maps identified an unexpected
      evolutionary stability of chromosomes in fish, in contrast to in mammals. Genes
      associated with viviparity show signatures of positive selection, identifying new
      putative functional domains and rare cases of parallel evolution. We also find
      that genes implicated in cognition show an unexpectedly high rate of duplicate
      gene retention after the teleost genome duplication event, suggesting a
      hypothesis for the evolution of the behavioral complexity in fish, which exceeds
      that found in amphibians and reptiles.

PMID- 23542701
TI  - Mutations of DEPDC5 cause autosomal dominant focal epilepsies.
AB  - The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe
      epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with
      variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain
      containing protein 5) was identified in a family with focal epilepsy with
      variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing
      of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified
      4 nonsense mutations and 1 missense mutation. Our findings provided evidence of
      frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad
      spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and
      Pleckstrin) domain-containing protein that may be involved in membrane
      trafficking and/or G protein signaling opens new avenues for research.

PMID- 23542702
TI  - 3D printing of preclinical X-ray computed tomographic data sets.
AB  - Three-dimensional printing allows for the production of highly detailed objects
      through a process known as additive manufacturing. Traditional, mold-injection
      methods to create models or parts have several limitations, the most important of
      which is a difficulty in making highly complex products in a timely, cost
      effective manner.(1) However, gradual improvements in three-dimensional printing
      technology have resulted in both high-end and economy instruments that are now
      available for the facile production of customized models.(2) These printers have
      the ability to extrude high-resolution objects with enough detail to accurately
      represent in vivo images generated from a preclinical X-ray CT scanner. With
      proper data collection, surface rendering, and stereolithographic editing, it is
      now possible and inexpensive to rapidly produce detailed skeletal and soft tissue
      structures from X-ray CT data. Even in the early stages of development, the
      anatomical models produced by three-dimensional printing appeal to both educators
      and researchers who can utilize the technology to improve visualization
      proficiency. (3, 4) The real benefits of this method result from the tangible
      experience a researcher can have with data that cannot be adequately conveyed
      through a computer screen. The translation of pre-clinical 3D data to a physical
      object that is an exact copy of the test subject is a powerful tool for
      visualization and communication, especially for relating imaging research to
      students, or those in other fields. Here, we provide a detailed method for
      printing plastic models of bone and organ structures derived from X-ray CT scans
      utilizing an Albira X-ray CT system in conjunction with PMOD, ImageJ, Meshlab,
      Netfabb, and ReplicatorG software packages.

PMID- 23542703
TI  - Chicken NK cell receptors.
AB  - Natural killer cells are innate immune cells that destroy virally infected or
      transformed cells. They recognize these altered cells by a plethora of diverse
      receptors and thereby differ from other lymphocytes that use clonally distributed
      antigen receptors. To date, several receptor families that play a role in either
      activating or inhibiting NK cells have been identified in mammals. In the
      chicken, NK cells have been functionally and morphologically defined, however, a
      conclusive analysis of receptors involved in NK cell mediated functions has not
      been available. This is partly due to the low frequencies of NK cells in blood or
      spleen that has hampered their intensive characterization. Here we will review
      recent progress regarding the diverse NK cell receptor families, with special
      emphasis on novel families identified in the chicken genome with potential as
      chicken NK cell receptors.

PMID- 23542704
TI  - Regulation of macrophage and dendritic cell function by pathogens and through
      immunomodulation in the avian mucosa.
AB  - Macrophages (MPh) and dendritic cells (DC) are members of the mononuclear
      phagocyte system. In chickens, markers to distinguish MPh from DC are lacking,
      but whether MPh and DC can be distinguished in humans and mice is under debate,
      despite the availability of numerous markers. Mucosal MPh and DC are
      strategically located to ingest foreign antigens, suggesting they can rapidly
      respond to invading pathogens. This review addresses our current understanding of
      DC and MPh function, the receptors expressed by MPh and DC involved in pathogen
      recognition, and the responses of DC and MPh against respiratory and intestinal
      pathogens in the chicken. Furthermore, potential opportunities are described to
      modulate MPh and DC responses to enhance disease resistance, highlighting
      modulation through nutraceuticals and vaccination.

PMID- 23542705
TI  - Molecular evolution of a polymorphic HSP40-like protein encoded in the
      histocompatibility locus of an invertebrate chordate.
AB  - Allorecognition, the ability to distinguish self from non-self, occurs in most
      organisms. Despite the ubiquity of the allorecognition process, the genetic basis
      for allorecognition remains unexplored in most taxa outside vertebrates and
      flowering plants. The allorecognition system in the colonial ascidian Botryllus
      schlosseri is a notable exception. We have recently identified a polymorphic gene
      within the fuhc locus that may play a role in allorecognition. The encoded
      protein, called Hsp40-L, is a Type II member of the J-protein family which
      usually functions as a co-chaperone with Hsp70. While many of the residues that
      interact with Hsp70 are conserved in Hsp40-L, it may not be a housekeeping
      protein because it is surprisingly polymorphic and expressed in the ampullae, the
      site of allorecognition. While the majority of the Hsp40-L protein appears to
      evolve under purifying selection, a section of the C-terminal region likely
      experiences balancing/directional selection, characteristic of other
      allorecognition proteins. 

PMID- 23542706
TI  - Parasitic incidence in a cyprinid fish Labeo rohita (Ham.) at river Song in Doon
      valley (Uttarakhand).
AB  - On examining 144 specimens of Labeo rohita (Ham.) for parasites occurrence; as
      many as 34 fish were found positive to harbour ciliophorans (Trichodina sp. and
      Ichthyophthirius multifilis Fouquet, 1876), monogeneans (Haplocleidus vachi
      Tripathi, 1959 and Dactylogyrus glossogobii Jain, 1960), trematode (Allocreadium
      mahaseri Pandey, 1939), nematode (Camallanus (Zeylanema) anabantis Pearse, 1933)
      and acanthocephalan (Sachalinorhynchus sp). Highest prevalence was shown by
      platyhelminthes (18.75%) followed by ciliophorans (10.41%), nematode (4.16%) and
      acanthocephalan (2.77%) in succession. Maximum mean intensity and abundance has
      been shown by C. (Zeylanema) anabantis Pearse, 1933 while the monogenean H. vachi
      was on the 2nd rank. On the other hand, the least intensity and abundance was
      shown by Ichthyophthirius multifilis. The prevalence was recorded more in monsoon
      (52.77%) followed by post-monsoon (22.22%), summer (19.44%) and winter (8.33%) in
      succession. Further, the unit-wise intensity of parasites was recorded more in
      males than the females.

PMID- 23542707
TI  - Left-sided gallbladder discovered during laparoscopic cholecystectomy in a
      patient with dextrocardia.
AB  - Left-sided gallbladder, a rare congenital anomaly, is often associated with
      transposition of single or multiple viscera of thorax and/or abdomen. Clinical
      features and routine presurgical ultrasonography could miss the anomalous
      position thereby producing unnecessary anxiety during surgery. Here we are
      reporting a patient with left-sided gallbladder, known to have dextrocardia with
      multiple intracardiac anomalies, and detected incidentally in a series of 1258
      consecutive laparoscopic cholecystectomies. Laparoscopic cholecystectomy was
      performed successfully in this patient with port site modification and careful
      dissection. Some degree of abdominal visceral situs inversus is to be anticipated
      in patients with dextrocardia.

PMID- 23542708
TI  - Comparing the Daily Versus the Intermittent Regimens of the Anti-Tubercular
      Chemotherapy in the Initial Intensive Phase in Non-HIV, Sputum Positive,
      Pulmonary Tuberculosis Patients.
AB  - BACKGROUND: Tuberculosis (TB) is a major health problem in the universe and India
      is no longer exempted from this crisis .The emergence of HIV and MDRTB (Multi
      Drug Resistant Tuberculosis) have further made the situation critical. AIMS: Our
      aim was to compare the efficacy of the daily and the intermittent doses of the
      Anti Tubercular Drug (ATD) therapy which is under the Revised National
      Tuberculosis Control Programme, amongst the sputum positive pulmonary
      tuberculosis in terms of the sputum conversion rate at the end of the initial
      phase , the default rate and the adverse drug reactions. METHODS: This was an
      observational prospective study. MATERIAL: Eighty three patients were selected
      from the out patient and the inpatient departments of a tertiary medical centre
      in India. RESULTS: Forty three cases received an intermittent regimen, where the
      major age group belonged to the under 40 years age group, the default rate to the
      therapy was 9.3%, the sputum conversion rate was 94.87% and adverse drug
      reactions were found in 25.58% of the patients. In the daily regimen, there was
      an equal proportion of the age group of the patients, both above and below 40
      yrs, the sputum conversion rate was 94.74%, a default rate was found in 5% cases
      and adverse reactions were found in 35% of the cases. CONCLUSION: Both the
      intermittent and the daily regimens showed equal sputum conversion rates and the
      drug default cases were found more in the intermittent group. However, the
      adverse reactions were found more in the daily regimen category.

PMID- 23542709
TI  - Ringxiety and the Mobile Phone Usage Pattern among the Students of a Medical
      College in South India.
AB  - AIMS: Technologies like mobile phones may not always work positively but they may
      have unforeseen adverse effects. This study was conducted to find the proportion
      of students who experienced ringxiety (phantom ringing) and other perceived
      effects, as well as the pattern of the mobile phone usage among college students.
      METHOD: A cross-sectional study was carried out at Kasturba Medical College,
      Mangalore, south India, among 336 medical students by using a pre-tested, semi
      structured questionnaire. RESULTS: Among the total number of students, 335
      students possessed mobile phones. Mostly, the persons whom they talked to on
      their phones were parents for 220 (51%) of the students. 48% (150) talked for
      less than half hour in a day and 41% (137) were high volume message users.
      "Ringxiety" was experienced by 34.5% (116) of the students and they were more
      likely to use their phones at restricted places like classrooms (99%) and
      libraries (60.3%). A significantly larger proportion of ringxiety sufferers also
      complained of hampered studies. CONCLUSION: The pattern of mobile phone use among
      the medical students appeared to be problematic, as a fairly large proportion
      suffered from ringxiety, they reported getting very upset and they used their
      phones at restricted times and places. This problem needs to be recognized, all
      stakeholders must be made aware of the symptoms and measures must be taken to
      reduce it.

PMID- 23542710
TI  - Anatomy of the inferior orbital fissure: implications for endoscopic cranial base
      surgery.
AB  - Considering many approaches to the skull base confront the inferior orbital
      fissure (IOF) or sphenomaxillary fissure, the authors examine this anatomy as an
      important endoscopic surgical landmark. In morphometric analyses of 50 adult
      human dry skulls from both sexes, we divided the length of the IOF into three
      segments (anterolateral, middle, posteromedial). Hemotoxylin- and eosin-stained
      sections were analyzed. Dissections were performed using transnasal endoscopy in
      four formalin-fixed cadaveric cranial specimens (eight sides); three endoscopic
      approaches to the IOF were performed. IOF length ranged from 25 to 35 mm (mean 29
      mm). Length/width of the individual anterolateral, middle, and posteromedial
      segments averaged 6.46/5, 4.95/3.2, and 17.6/ 2.4 mm, respectively. Smooth muscle
      within the IOF had a consistent relationship with several important anatomical
      landmarks. The maxillary antrostomy, total ethmoidectomy approach allowed access
      to the posteromedial segment of the fissure. The endoscopic modified, medial
      maxillectomy approach allowed access to the middle and posterior-medial segment.
      The Caldwell-Luc approach allowed complete exposure of the IOF. The IOF serves as
      an important anatomic landmark during endonasal endoscopic approaches to the
      skull base and orbit. Each of the three segments provides a characteristic
      endoscopic corridor, unique to the orbit and different fossas surrounding the
      fissure.

PMID- 23542711
TI  - On the occurrence of a gregarine parasite (Apicomplexa: Eugregarinorida) from the
      seminal vesicles of earthworms (Annelida: Oligochaeta) of Bangladesh.
AB  - In a survey of the endoparasitic acephaline gregarines in the Satkhira district
      of Bangladesh, seminal vesicles of earthworm, Metaphire posthuma were found to be
      infested with a new species of the genus Enterocystis Tsvetcov 1926, Enterocystis
      elongatum sp. nov. The new species is elongated and measures 55.3-87.8 (67.7 +/-
      10.3) MUm in length and 33.2-37.8 (35.7 +/- 1.6) MUm in width. Nucleus ovoid and
      measures 4.4-8.8 (6.6 +/- 2.2) MUm in length and 4.4-6.6 (5.3 +/- 1.1) MUm in
      width. Gametocyst with two unequal sized gametocytes and measures 88.4-101.7 MUm
      (97.9 +/- 4.8) MUm in length and 77.6-95.0 (86.9 +/- 7.7) MUm in width. Oocysts
      ellipsoidal and measure 13.7-19.9 (16.7 +/- 2.6) MUm in length and 6.6-8.8 (7.6
      +/- 1.1) MUm in width. Prominent association or syzygy is present in life cycle.

PMID- 23542712
TI  - The effects of alpha-defensin 1 on electrical field stimulation-induced
      contraction of rat bladders.
AB  - This study was designed to investigate the effects of alpha-defensin 1 on
      electrical field stimulation (EFS)-induced contractions in isolated rat bladder
      detrusor muscles. We evaluated the effects of alpha-defensin 1 (50 pM~5 nM) on
      EFS-induced contractions in the detrusor smooth muscles from 35 rats (2-30 Hz).
      Bladder strips were pretreated with alpha-defensin 1 and then changes of
      contractions by adenosine 5'-triphosphate (ATP) were observed. Moreover, after
      pretreatment with alpha-defensin 1 for 10 min, changes in concentration-response
      curves to hydrogen peroxide (H2O2) were investigated. Alpha-defensin 1 has
      increased EFS-induced contractions, significantly, and the contractile response
      to ATP (1,2,5,10mM) was also increased significantly when strips were pretreated
      with alpha-defensin 1. In addition, alpha-defensin 1 increased H2O2-induced
      contractions. The present study demonstrates that alpha-defensin 1 increases EFS
      induced contractions of rat detrusor muscles via purinergic contraction coupled
      with the Rho kinase pathway.

PMID- 23542713
TI  - Activation of a retinoic acid receptor pathway by thiazolidinediones induces
      production of vascular endothelial growth factor/vascular permeability factor in
      OP9 adipocytes.
AB  - Thiazolidinediones, ligands of peroxisome proliferator-activated receptorgamma
      (PPARgamma), are used in the management of type 2 diabetes mellitus. However,
      they can cause edema, which often leads to a discontinuation of treatment. The
      mechanism by which thiazolidinediones induce edema is poorly understood. We have
      confirmed that troglitazone (TGZ), a thiazolidinedione, induced the
      differentiation of a preadipocyte cell line, OP9, into adipocytes. The
      differentiated OP9 cells produced vascular permeability factors and the activity
      was completely neutralized by an antibody against vascular endothelial growth
      factor (VEGF). TGZ induced the expression of VEGF but not interleukin-6 and
      monocyte chemoattractant protein-1. 2-chloro-5-nitrobenzanilide (GW9662) blocked
      both the differentiation and the production of VEGF induced by TGZ. 15-deoxy
      Delta(12,14)-Prostaglandin J2, a natural ligand of PPARgamma, and another
      PPARgamma agonist, ginkgolic acid, also induced an increase in the expression of
      VEGE as well as the differentiation of OP9 cells. Indomethacin, a nonsteroidal
      anti-inflammatory drug (NSAID) with PPARgamma activity, up-regulated VEGF
      expression, but acetylsalicylic acid, a NSAID without PPARgamma activity, did
      not. Although VEGF expression was enhanced under hypoxic conditions, the
      expression of hypoxia inducible factor and Ets-1 was down-regulated during the
      TGZ-induced differentiation. On the other hand, retinoic acid enhanced the
      expression of VEGF despite inhibiting the TGZ-induced differentiation. Moreover,
      retinoic acid receptor (RAR) beta expression was increased by TGZ and retinoic
      acid. These findings suggested that the major adipocyte-derived vascular
      permeability factor produced in response to TGZ was VEGF, and a RAR pathway was
      involved in the production.

PMID- 23542715
TI  - Benign atypical intravascular CD30(+) T-cell proliferation: a reactive condition
      mimicking intravascular lymphoma.
AB  - CD30 is a transmembrane glycoprotein molecule usually expressed in activated B
      and T cells. Although it has been considered a reliable marker for CD30
      lymphomas, reactive inflammatory disorders may contain a significant number of
      CD30 cells mimicking lymphoproliferative disorders clinically or histologically.
      Intravascular lymphoma is a rare variant of non-Hodgkin lymphoma that can involve
      the skin in 40% of the patients. The majority of cases show a B-cell phenotype,
      and only a minority of cases are of T-cell or NK-cell origin. Moreover, 2
      aggressive cases of intravascular large T-cell lymphoma have been described with
      a CD30 phenotype. Herein, we report 2 patients with skin lesions showing an
      atypical intravascular CD30 T-cell proliferation. Both the patients did not
      present systemic disease and therefore exhibit a favorable outcome. To the best
      of our knowledge, this is the second report in the literature of a benign
      intravascular CD30 T-cell proliferation that represents an intriguing
      differential diagnosis for intravascular lymphoma.

PMID- 23542714
TI  - Non-enzymatic modifications in metallothioneins connected to lipid membrane
      damages: structural and biomimetic studies under reductive radical stress.
AB  - Metallothioneins (MTs) are small cysteine-rich proteins with the ability to
      coordinate heavy metal atoms through metal-thiolate bonds, which are widely
      distributed among the animal and plant kingdoms. Multifunctional roles for MTs
      have been proposed, including their ability to scavenger various radicals and
      reactive oxygen species. In the present article we summarize available
      information of four MT polypeptides from different organisms, forming metal
      complexes with Zn(II), Cd(II) or Cu (I) ions. Non-enzymatic modifications of MTs
      under ionizing radiations and their consequences on the lipidic membrane
      compartment were studied by Raman spectroscopy and a biomimetic model,
      respectively. The latter is based on liposome technology and allows to measure
      the trans unsaturated fatty acid content as a result of reductive radical stress
      on MTs. BIOLOGICAL SIGNIFICANCE: The effect of radical stress on the cell
      metabolism and functions is a very active field of research connecting various
      disciplines in life sciences. In this contest tandem radical damage has been the
      subject of recent investigations that pointed out its harmfulness in the general
      scenario of establishing the consequences of radical stress. By using biomimetic
      models of tandem damage we have for the first time tested the capability of
      metallothioneins (MTs), small metalloproteins rich of Cys residues, to damage
      another cell compartment like lipid membranes when they are undergone to
      reductive radical stress. The connection of MT reactivity with membrane lipid
      transformation can give a contribution to the puzzling context of radical stress
      occurring to biomolecules and the role as biological signaling. To this purpose,
      MT polypeptides from different organisms, exhibiting different sequence
      peculiarities, have been analyzed here. The spectroscopic analysis of these
      systems has allowed to identify modifications affecting metal-thiolate clusters,
      cystines, and Met residues, acting as efficient interceptors of reducing radical
      species. The chemical mechanism involving sulfur-containing moieties under
      reductive conditions discloses new scenarios that bring to the loss of sulfur
      centered radicals by desulfurization reactions that change the natural sequences
      of MTs. Ala is a genetically coded amino acid, therefore the mutation of Cys to
      Ala occurring to a sequence by the radical process so far discussed, corresponds
      to a post-translational modification. Research on such mutation connected also to
      a free radical stress will be important to contribute for a complete picture of
      the degeneration associated to diseases and aging. Analogously, the Met to Aba
      mutation occurring after reductive stress transforms a natural amino acid into a
      natural, non-genetically-coded congener. Aba corresponds to a homologation of the
      alkyl chains normally present in genetically codified amino acids, such as methyl
      (in Ala) and isopropyl (in Leu), with an ethyl unit. Based on alkyl substitution,
      this modification can therefore be studied in order to understand its general
      consequences on the structure-activity relationships in proteins and, in
      particular, on molecular interactions. This article is part of a Special issue
      entitled: Posttranslational Protein modifications in biology and Medicine.

PMID- 23542716
TI  - Two-dimensional visualization of multicolor FISH-generated data as a helpful tool
      for the analysis and understanding of cytogenetic and chromosomal alterations in
      melanocytic lesions.
AB  - For the evaluation of data generated by multicolor fluorescence in situ
      hybridization (FISH), we present here a synergistic approach that integrates the
      3 most commonly used numerical algorithms in conjunction with 2 newly devised
      graphic tools for data visualization, namely "signal curves" and "rhombic heat
      maps." These two graphic tools provide information additional to the currently
      used numerical algorithms and thus facilitate the recognition and compensation of
      inherent errors that occur with the numerical method.

PMID- 23542717
TI  - Syndrome of Birt-Hogg-Dube, a histopathological pitfall with similarities to
      tuberous sclerosis: a report of three cases.
AB  - Birt-Hogg-Dube Syndrome (BHD) is a rare condition, transmitted as an autosomal
      dominant trait. The etiology is due to a mutation in the BHD gene, which encodes
      folliculin (FLCN), located on chromosome 17p. The skin changes observed are
      benign skin tumors consisting of hamartomas of the hair follicle with dermal
      changes. Patients with BHD have an increased risk of spontaneous pneumothorax due
      to rupture of lung cysts and an increased risk of kidney tumors. We report 3 new
      cases of BHD and discuss their clinical features, histopathological findings, and
      molecular diagnostics. We highlight the importance of genetic analysis to confirm
      the diagnosis because of the clinical pitfalls involved in establishing a
      diagnosis. Finally, we discuss the histopathological features in BHD and tuberous
      sclerosis complex and focus on their overlapping criterias. A correct diagnosis
      is essential as it can be life saving for patients.

PMID- 23542718
TI  - Cutaneous metastases can be the initial presenting sign of a cardiac sarcoma.

PMID- 23542719
TI  - Essential thrombocythemia presenting as localized livedo reticularis.
AB  - Essential thrombocythemia is a chronic myeloproliferative disorder characterized
      by a persistent and absolute increase in the peripheral platelet count
      (>600,000/mm) in the absence of another underlying disorder. From a clinical
      point of view, it is characterized by thrombotic manifestations that primarily
      involve the central nervous system as strokes and transient ischemic attacks and
      also affects other systems, causing gastrointestinal hemorrhages and arterial or
      venous thrombosis. Cutaneous manifestations may complicate essential
      thrombocythemia, but they may be a helpful guide to the diagnosis. These
      manifestations appear up to 22% of patients and may even be the presenting sign
      of the disease in up to 10% of them. We present a case of a previously healthy
      woman who was diagnosed with essential thrombocythemia after the onset of
      localized livedo reticularis. The case was immunohistochemically studied,
      supporting the role of the increased platelet number in the pathogenesis of the
      livedo reticularis lesions.

PMID- 23542721
TI  - A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active
      metabolites of clopidogrel in human plasma: application to a clinical
      pharmacokinetic study.
AB  - Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent
      myocardial infarction, recent stroke, or established peripheral arterial disease.
      A sensitive and reliable high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable
      quantification of four diastereomeric and chemically reactive thiol metabolites,
      two of which are pharmacologically active, in human plasma. The metabolites were
      stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'
      methoxyacetophenone (MPB). Following organic solvent mediated-protein
      precipitation in a 96-well plate format, chromatographic separation was achieved
      by gradient elution on an Ascentis Express RP-amide column. Chromatographic
      conditions were optimized to ensure separation of the four derivatized active
      metabolites. Derivatized metabolites and stable isotope-labeled internal
      standards were detected by positive ion electrospray tandem mass spectrometry.
      The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL
      for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay
      precision values for replicate quality control samples were within 14.3% for all
      analytes during the assay validation. Mean quality control accuracy values were
      within +/-6.3% of nominal values for all analytes. Assay recoveries were high
      (>79%). The four derivatized analytes were stable in human blood for at least 2 h
      at room temperature and on ice. The analytes were also stable in human plasma for
      at least 25 h at room temperature, 372 days at -20  degrees C and -70  degrees C,
      and following at least five freeze-thaw cycles. The validated assay was
      successfully applied to the quantification of all four thiol metabolites in human
      plasma in support of a human pharmacokinetic study.

PMID- 23542722
TI  - Determination of dapoxetine in rat plasma by ultra-performance liquid
      chromatography-tandem mass spectrometry.
AB  - In this study, we describe and validate a rapid and sensitive method for
      quantitation of dapoxetine in rat plasma by using ultra-performance liquid
      chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS).
      Plasma samples were prepared by protein precipitation with acetonitrile, and
      sildenafil was used as an internal standard (IS). The mobile phase consisted of
      0.5% formic acid/acetonitrile (60:40, v/v); a C18 reversed-phase column (2.0 * 50
      mm, 1.7 MUm) was used for chromatographic separation. Multiple reaction
      monitoring (MRM) was used in the positive ion mode for mass spectrometric
      detection. The calibration curve for dapoxetine was linear (r(2)=0.999) in the
      concentration range of 1-500 ng/mL. The intra- and inter-day precision was
      between 3.8% and 8.3%, and the intra- and inter-day accuracy was between 101.1%
      and 109.0%. Dapoxetine was found to be stable in various conditions with the
      recoveries>87.0% (RSD <7.2%). The method was found to be specific, precise, and
      accurate, and no matrix effect was observed. Our results suggest that this method
      can be successfully applied in pharmacokinetic studies of dapoxetine in rat
      plasma.

PMID- 23542723
TI  - Seasonality of vitamin D status in older people in Southern Germany: implications
      for assessment.
AB  - BACKGROUND: from a clinical and public health perspective, it is important to
      understand the influence of seasonality on the serum vitamin D level to
      adequately assess and interpret an individual measurement. Therefore, the aim of
      this study was to analyse the effects of seasonal conditions on 25-hydroxyvitamin
      D (25(OH)D) serum levels in a population-based cohort of older people. METHODS:
      between March 2009 and April 2010 the 25(OH)D serum level was assessed in 1,418
      community-dwelling individuals living in Germany aged >=65 years (56.7% men) with
      no subscribed vitamin D supplementation. Least-square means of monthly 25(OH)D
      serum levels with 95% confidence intervals (CI) were estimated, adjusted for
      gender, age and body mass index. Additionally, the proportion of vitamin
      deficiency (<20 ng/ml), insufficiency (20-<30 ng/ml) and sufficiency (30 ng/ml or
      higher) were estimated for each month. Finally, mean values of daily total global
      solar radiation and daylight were calculated for each month. RESULTS: the minimum
      25(OH)D serum level was observed in March with 15.4 ng/ml (SD = 6.56 ng/ml) and
      the maximum in August with 25.6 ng/ml (SD = 6.59 ng/ml). Compared with daylight
      and global solar radiation the progression over the year was similar but delayed
      by ~2 months. The proportion of vitamin D deficiency, insufficiency and
      sufficiency were 78.8, 19.2 and 1.9% in March and 16.1, 63.4 and 20.5% in August,
      respectively. CONCLUSION: vitamin D insufficiency was very common in this cohort
      and showed a strong seasonal effect with lowest values in March.

PMID- 23542720
TI  - Leptin as regulator of pulmonary immune responses: involvement in respiratory
      diseases.
AB  - Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the
      balance between food intake and energy expenditure by signalling through its
      functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to
      the long-chain helical cytokine family, and is now known to have pleiotropic
      functions in both innate and adaptive immunity. The presence of the functional
      leptin receptor in the lung together with evidence of increased airspace leptin
      levels arising during pulmonary inflammation, suggests an important role for
      leptin in lung development, respiratory immune responses and eventually
      pathogenesis of inflammatory respiratory diseases. The purpose of this article is
      to review our current understanding of leptin and its functional role on the
      different resident cell types of the lung in health as well as in the context of
      three major respiratory conditions being chronic obstructive pulmonary disease
      (COPD), asthma, and pneumonia.

PMID- 23542724
TI  - Allopurinol use is associated with greater functional gains in older
      rehabilitation patients.
AB  - INTRODUCTION: the xanthine oxidase system produces reactive oxidative species and
      its inhibition by allopurinol has been shown to have beneficial effects on
      cardiovascular function. Oxidative stress has also been implicated in the
      development of sarcopenia. Allopurinol, a xanthine oxidase inhibitor, both
      reduces oxidative stress and acts as a potential oxygen-sparing agent. We
      examined the association between allopurinol use and functional outcomes after
      rehabilitation in a cohort of older people. METHODS: analysis of routinely
      collected clinical data from a single rehabilitation unit. Data were
      prospectively collected on all admissions to the Dundee Medicine for the Elderly
      rehabilitation unit between 1 January 1999 and 31 December 2008. Multivariate
      analyses were performed to examine the difference between the 20-point Barthel
      score on admission and discharge, adjusting for age, sex, admission Barthel
      score, anti-platelet use and comorbid disease. RESULTS: a total of 3,593 patients
      were included in the analysis and 3% of patients were taking allopurinol on
      discharge (n = 102). Improvement in Barthel scores was greater in the allopurinol
      group than the non-allopurinol group (4.7 versus 3.6 points, mean difference 1.1,
      95% CI: 0.4-1.8, P = 0.002). When adjusted for age, sex, admission Barthel,
      presenting disease and number of drugs on discharge, improvement in the Barthel
      score was still greater in the allopurinol group (4.8 versus 3.8 points, mean
      difference 0.94, 95% CI: 0.3 to 1.6, P = 0.006). CONCLUSIONS: this retrospective
      observational study suggests that allopurinol use is associated with a greater
      degree of improvement in function as measured by the Barthel score during
      rehabilitation in an older inpatient population. Prospective randomised
      controlled trials are required to further investigate this finding.

PMID- 23542725
TI  - Partial claviculectomy after non-union of proximal clavicle fracture.
AB  - Non-union of a proximal clavicle fracture is rare. When it does occur, it poses a
      difficult problem causing severe pain and shoulder impairment that must be dealt
      with surgically. We report a 29-year-old woman who suffered a proximal clavicle
      fracture and received plate and screws fixation. Six months later, after constant
      pain and a diminished range of shoulder motion, she sought help at our clinic and
      was diagnosed with symptomatic non-union. Reconstruction with bone graft and
      interosseous sutures was performed in vain as pain persisted and follow-up
      radiograph showed no healing. A salvage procedure with partial claviculectomy was
      then carried out. The patient has been pain free after 3.5 years of follow-up, a
      full range of motion and is quite satisfied with the cosmetics. This outcome
      demonstrates that claviculectomy can be used successfully in a clinical situation
      where restoration of clavicular non-union fails.

PMID- 23542726
TI  - Puerperal development of ewes following dystocia: a retrospective analysis of two
      approaches to caesarean section.
AB  - The objective of this study was to retrospectively analyse the puerperal
      development of ewes referred to a veterinary teaching hospital following
      caesarean section in comparison with assisted parturition. Laparotomy was
      performed either via left flank incision (group 1, n=86) or ventral mid-line
      approach (group 2, n=33). Both groups were compared with ewes following non
      surgical intervention (group 3, n=73). The overall fetal death rate was 41 per
      cent. There was no significant difference in fetal deaths between groups 1 and 2,
      but assisted delivery led to a higher number of liveborn lambs compared with
      caesarean section (P<0.05). Seven ewes (3.6 per cent) died or were euthanased on
      welfare grounds during caesarean surgery, and the overall maternal mortality rate
      following dystocia in the postpartum period was 10.9 per cent. While there was no
      significant difference between groups 1 and 2 in the percentage of ewes
      developing healing disorders, the complications that occurred were more severe
      after the left flank approach (P=0.04), and the mean hospitalisation period was
      significantly longer in group 1 than in group 2 (P<0.05), leading to the
      conclusion that ventral mid-line laparotomy has some advantages over a left flank
      approach.

PMID- 23542728
TI  - Neurophysiological investigation of phonological input: aging effects and
      development of normative data.
AB  - The current study investigated attended and unattended auditory phoneme
      discrimination using the P300 and Mismatch Negativity event-related potentials
      (ERPs). Three phonemic contrasts present in the Dutch language were compared.
      Additionally, auditory word recognition was investigated by presenting rare
      pseudowords among frequent words. Two main goals were: (1) obtain normative data
      for ERP latencies (ms) and amplitudes (MUV) and (2) examine aging influences.
      Seventy-one healthy subjects (21-83 years) were included. During phoneme
      discrimination aging was associated with increased latencies and decreased
      amplitudes. However, a discrepancy between attended and unattended processing, as
      well as between phonemic contrasts, was found. During word recognition aging only
      had an impact on ERPs elicited by real words, indicating that mainly semantic
      processes were altered leaving lexical processes unharmed. Early sensory
      perceptual processes, reflected by N100 and P50, were free from aging influences.
      In future, neurophysiological normative data can be applied in the evaluation of
      acquired language disorders.

PMID- 23542727
TI  - Distinct regional anatomic and functional correlates of neurodegenerative apraxia
      of speech and aphasia: an MRI and FDG-PET study.
AB  - Progressive apraxia of speech (AOS) can result from neurodegenerative disease and
      can occur in isolation or in the presence of agrammatic aphasia. We aimed to
      determine the neuroanatomical and metabolic correlates of progressive AOS and
      aphasia. Thirty-six prospectively recruited subjects with progressive AOS or
      agrammatic aphasia, or both, underwent the Western Aphasia Battery (WAB) and
      Token Test to assess aphasia, an AOS rating scale (ASRS), 3T MRI and 18-F
      fluorodeoxyglucose (FDG) PET. Correlations between clinical measures and imaging
      were assessed. The only region that correlated to ASRS was left superior premotor
      volume. In contrast, WAB and Token Test correlated with hypometabolism and volume
      of a network of left hemisphere regions, including pars triangularis, pars
      opercularis, pars orbitalis, middle frontal gyrus, superior temporal gyrus,
      precentral gyrus and inferior parietal lobe. Progressive agrammatic aphasia and
      AOS have non-overlapping regional correlations, suggesting that these are
      dissociable clinical features that have different neuroanatomical underpinnings.

PMID- 23542729
TI  - Liver X receptors: emerging therapeutic targets for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder, typified by the
      pathological accumulation of beta-amyloid peptides (Abeta) and neurofibrillary
      tangles within the brain, culminating to cognitive impairment. Epidemiological
      and biochemical data have suggested a link between cholesterol content, APP
      (amyloid precursor protein) processing, Abeta, inflammation and AD. The intricacy
      of the disease presents considerable challenges for the development of newer
      therapeutic agents. Liver X receptors (LXRa and LXRbeta) are oxysterol activated
      nuclear receptors that play essential role in lipid and glucose homeostasis,
      steroidogenesis and inflammatory responses. LXR signalling impacts the
      development of AD pathology through multiple pathways. Reports indicate that
      genetic loss of either lxra or lxrbeta in APP/PS1 transgenic mice results in
      increased amyloid plaque load. Studies also suggest that ligand activation of
      LXRs in Tg2576 mice enhanced, the expression of genes linked with cholesterol
      efflux e.g. apoe, abca-1, down regulated APP processing and Abeta production with
      significant improvement in memory functions. LXR agonists have also depicted to
      inhibit neuroinflammation through modulation of microglial phagocytosis and by
      repressing the expression of cox2, mcp1 and iNos in glial cells. This review
      summarizes in brief the biology of LXRs, with an emphasis on their probable
      pathophysiological mechanisms that may elicit the defending role of these
      receptors in brains of AD patients.

PMID- 23542730
TI  - Statins decrease all-cause mortality only in CKD patients not requiring dialysis
      therapy--a meta-analysis of 11 randomized controlled trials involving 21,295
      participants.
AB  - The available studies have reported the benefits of statins on all-cause and
      cardiovascular mortality in chronic kidney disease (CKD) patients. However
      studies in end-stage renal disease patients on dialysis yielded conflicting
      results. Therefore, we performed a meta-analysis and provide the most reliable
      trial data to date on the impact of statin therapy on cardiovascular events and
      death from all causes in CKD patients. Data from PubMed, Web of Science, Cochrane
      Library, and Scopus for the years 1966 to October 2012 were searched. The final
      meta-analysis included 11 randomized controlled trials involving 21,295
      participants with CKD. Among them 6857 were on dialysis. The use of statins in
      subjects with non-dialysis-dependent CKD resulted in a marked reduction in death
      from all causes (relative risk [RR]: 0.66; 95% confidence interval [CI]: 0.55
      0.79; p<0.0001), cardiac causes (RR: 0.69; 95%CI: 0.55-0.68; p=0.0012),
      cardiovascular events (RR: 0.55; 95%CI: 0.4-0.75; p=0.0001) and stroke (RR: 0.66;
      95%CI: 0.5-0.88; p=0.0022). The use of statins in dialysis-dependent CKD patients
      resulted in a non-significant effect on death from all causes (RR: 0.99; 95%CI:
      0.88-1.11; p=0.85) and stroke (RR: 1.31; 95%CI: 0.9-1.89; p>0.05), but had the
      effect of reducing death from cardiac causes (RR: 0.79; 95%CI: 0.64-0.98; p<0.05)
      and cardiovascular events (RR: 0.81; 95%CI: 0.7-0.94; p<0.05). In conclusion, the
      use of statins should be indicated in cardiovascular disease prevention
      especially in patients with non-dialysis-dependent CKD. According to the very
      limited data the obtained results suggest caution in expecting a reduction in
      cardiovascular events in patients on dialysis.

PMID- 23542731
TI  - HPTLC method for the assay of thiopental in post-mortem blood in a fatal case of
      suicide.
AB  - Thiopental is an ultra-short-acting barbiturate, used as an induction agent
      during general anesthesia and to manage intra cranial pressure in traumatic brain
      injuries. Because of its rapid onset of action, the potential for accidental or
      intentional abuse of thiopental is high. In this paper, a case is presented in
      which a 25-year-old female deliberately injected a fatal dose of thiopental. A
      method is developed for the evaluation of thiopental levels in the post-mortem
      blood (PMB) by simple and rapid HPTLC. Three different extraction procedures were
      compared for optimum recovery of thiopental from spiked blood samples. The effect
      of pH on the extraction yield of thiopental over a pH range of 5-6.5 was
      examined. An average analytical recovery of 90.5% was achieved from an ethyl
      acetate extract at pH 5.5. Chromatographic separation was achieved on silica gel
      60F254 plates with an optimized mobile phase consisted of hexane-dichloromethane
      ethyl acetate in the ratio 7.5:2:0.5 (v/v). Densitometric detection was carried
      out at 290nm in absorbance mode. No significant chromatographic interference was
      observed from other drugs used to diagnose the brain death. Calibration curve for
      thiopental in blood were linear from 1 to 100MUgml(-1) with r(2)=0.994. The
      detection limit was 0.5MUgml(-1) and its lower limit of quantification was
      1.5MUgml(-1). The method showed excellent intra-assay precision (R.S.D. 1.07
      6.28%) and inter-assay precision (R.S.D. 0.39-1.43%) for spiked blood samples at
      concentration of 1, 10, and 50MUgml(-1). The toxicological analysis revealed high
      concentrations of thiopental in PMB (204.75MUgml(-1) +/-0.34), which is of
      immense help to conclude that the death occurred due to fatal doses of
      thiopental.

PMID- 23542732
TI  - Simultaneous qualitative and quantitative determination of phenolic compounds in
      Aloe barbadensis Mill by liquid chromatography-mass spectrometry-ion trap-time-of
      flight and high performance liquid chromatography-diode array detector.
AB  - An effective and comprehensive method was developed for the simultaneous analysis
      of phenolic compounds in the dried exudate of Aloe barbadensis Mill by liquid
      chromatography-mass spectrometry-ion trap-time-of-flight (LCMS-IT-TOF) and high
      performance liquid chromatography-diode array detector (HPLC-DAD). Qualitative
      analysis of all the compounds presented in A. barbadensis Mill was performed on
      LCMS-IT-TOF, and the diagnostic fragmentation patterns of different types of
      phenolic compounds (chromones, phenyl pyrones, naphthalene derivative, anthrones
      and anthraquinones) were discussed on the basis of ESI-IT-TOF MS of components in
      A. barbadensis Mill and eleven authentic standards. Under the optimal HPLC-DAD
      chromatographic conditions, quantification of 11 typical phenolic compounds in 15
      batches of A. barbadensis Mill was achieved on an Agilent TC-C18 column using
      gradient elution with a solvent system of methanol and water at a flow rate of
      1.0mLmin(-1) and detected at 230nm. All calibration curves exhibited good linear
      relationship (r(2)>0.9991). The relative standard deviation values for intraday
      precision were less than 2% with accuracies between 98.21% and 104.57%. The
      recoveries of the eleven analytes ranged from 97.53 to 105.00% with RSDs less
      than 2%. This is the first simultaneous characterization and quantitative
      determination of multiple phenolic compounds in A. barbadensis Mill from locally
      grown cultivars in China by LCMS-IT-TOF and HPLC-DAD, which can be applied to
      standardize the quality of A. barbadensis Mill and the future design of
      nutraceutical and cosmetic preparations.

PMID- 23542733
TI  - Development of a HPLC-UV method for the quantitative determination of four short
      chain fatty acids and lactic acid produced by intestinal bacteria during in vitro
      fermentation.
AB  - A rapid and sensitive HPLC-UV method for the quantitative determination of four
      short-chain fatty acids (SCFAs) and lactic acid (LA) produced during in vitro
      fermentation is presented. Extraction of SCFAs from supernatants of bacterial
      cultures is aggravated due to their polarity and volatility. Detection can only
      be performed at a short, non-selective UV wavelength (210nm), due to the lack of
      any significant chromophore. Therefore special attention was paid to the
      optimization of the sample preparation procedure and the HPLC-UV conditions. The
      final extraction procedure consisted of a liquid-liquid back extraction using
      diethylether. Prior to HPLC-UV analysis the samples were acidified (pH<2) in
      order to improve retention of the SCFA's and LA on the Hypersil Gold aQ column.
      Matrix-matched calibration graphs were prepared for all analytes of interest
      (range 0.5-50mM) and correlation and goodness-of-fit coefficients were between
      0.9951-0.9993 and 3.88-8.27%, respectively. Limits of detection and
      quantification ranged from 0.13 to 0.33mM and 0.5 to 1.0mM, respectively. The
      results for the within-day and between-day precision and accuracy fell within the
      ranges specified. The reported validated method has been successfully used for
      the in vitro screening of supernatants of bacterial cultures for the presence of
      butyric acid, aiming to select for butyric acid-producing bacteria. In addition,
      the method has been used to determine the production pattern of selected fatty
      acids by bacterial species isolated from human feces and chicken caeca.

PMID- 23542734
TI  - Angiogenic and inflammatory markers in acute respiratory distress syndrome and
      renal injury associated to A/H1N1 virus infection.
AB  - Acute kidney injury (AKI) is often associated to acute respiratory distress
      syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of
      angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We
      analyzed the serum levels of several angiogenic factors, cytokines, and
      chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15
      ARDS patients who did not developed AKI) and in 18 healthy controls.
      Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI
      patients were detected. Adjusting by confusing variables, levels of MCP-1 >=150
      pg/mL (OR=12.0, p=0.04) and VEGF >=225 pg/mL (OR=6.4, p=0.03) were associated
      with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10
      were significantly associated with a higher risk of death in patients with ARDS
      (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into
      account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over
      production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and
      are associated to a higher risk of death.

PMID- 23542735
TI  - Looking back on the birth of DEAD-box RNA helicases.
AB  - DEAD-box proteins represent the largest family of RNA helicases, present in all
      three kingdoms of life. They are involved in a variety of processes involving RNA
      metabolism and in some instances also in processes that use guide RNAs. Since
      their first descriptions in the late 1980s, the perception of their molecular
      activities has dramatically changed. At the time when only eight proteins with 9
      conserved motifs constituted the DEAD-box protein family, it was the biochemical
      characterization of mammalian eIF4A that first suggested a local unwinding
      activity. This was confirmed in vitro using partially double stranded RNA
      substrates with the unexpected result of a bidirectional unwinding activity. A
      real change of paradigm from the classical helicase activity to localized RNA
      unwinding occurred with the publication of the vasa*RNA structure with a bend in
      the RNA substrate and the insightful work from several laboratories demonstrating
      local unwinding without translocation. Finally, elegant work on the exon-junction
      complex revealed how DEAD-box proteins can bind to RNA to serve as clamps to
      function as nucleation centers to form RNP complexes. This article is part of a
      Special Issue entitled: The Biology of RNA helicases - Modulation for life.

PMID- 23542736
TI  - Temporally advanced dynamic change of receptive field of lateral geniculate
      neurons during brief visual stimulation: Effects of brainstem peribrachial
      stimulation.
AB  - Processing of visual information in the brain seems to proceed from initial fast
      but coarse to subsequent detailed processing. Such coarse-to-fine changes appear
      also in the response of single neurons in the visual pathway. In the dorsal
      lateral geniculate nucleus (dLGN), there is a dynamic change in the receptive
      field (RF) properties of neurons during visual stimulation. During a stimulus
      flash centered on the RF, the width of the RF-center, presumably related to
      spatial resolution, changes rapidly from large to small in an initial transient
      response component. In a subsequent sustained component, the RF-center width is
      rather stable apart from an initial slight widening. Several brainstem nuclei
      modulate the geniculocortical transmission in a state-dependent manner. Thus,
      modulatory input from cholinergic neurons in the peribrachial brainstem region
      (PBR) enhances the geniculocortical transmission during arousal. We studied
      whether such input also influences the dynamic RF-changes during visual
      stimulation. We compared dynamic changes of RF-center width of dLGN neurons
      during brief stimulus presentation in a control condition, with changes during
      combined presentation of the visual stimulus and electrical PBR-stimulation. The
      major finding was that PBR-stimulation gave an advancement of the dynamic change
      of the RF-center width such that the different response components occurred
      earlier. Consistent with previous studies, we also found that PBR-stimulation
      increased the gain of firing rate during the sustained response component.
      However, this increase of gain was particularly strong in the transition from the
      transient to the sustained component at the time when the center width was
      minimal. The results suggest that increased modulatory PBR-input not only
      increase the gain of the geniculocortical transmission, but also contributes to
      faster dynamics of transmission. We discuss implications for possible effects on
      visual spatial resolution.

PMID- 23542737
TI  - Perceptual errors increase with movement duration and may contribute to
      hypokinesia in Parkinson's disease.
AB  - People with Parkinson's disease (PD) perceive that their movement amplitude is
      greater than what they actually perform. The neural mechanisms underlying one's
      perception of movement are believed to involve the sensorimotor integration
      process (SIP). How PD affects the SIP is not well understood. A previous study
      interrogating the SIP showed healthy adults (HAs) overestimated their limb
      position in the direction of movement and the error and its variance (VOE)
      depended on movement duration. We asked if PDs showed errors in perceived limb
      position and if the dependence on movement duration was different from HAs. We
      used an existing computational model of the SIP to explore mechanisms for the
      error and VOE as a function of movement duration. Twenty PDs, off medication, and
      20 age-matched HAs were asked to estimate the position of their hand after
      performing 50, slow, non-visually guided wrist flexion or extension movements for
      a random period of time (<4.0 s). Both groups overestimated the amount they
      moved; however, the PDs' error and VOE were larger (p<0.001). HAs showed
      increasing error/VOE for small movement durations that reduced/stabilized for
      longer movement durations. PDs however showed increasing error/VOE with
      increasing movement duration that did not significantly improve/stabilize. The
      model suggested that the basis for such perceptual deficits may be abnormal
      proprioceptive feedback and/or processing of an abnormal internal impression
      (prediction) that underestimates movement amplitude. Simulation results imply
      that the PD's SIP could no longer effectively access sensory (proprioceptive)
      feedback to correct errors in other components of the SIP due to the abnormal
      processing of sensory feedback. We suggest from this study that an impaired
      perception of movement amplitude and sensory processing deficits contribute to
      hypokinesia in PD.

PMID- 23542738
TI  - Functional plasticity before the cradle: a review of neural functional imaging in
      the human fetus.
AB  - The organization of the brain is highly plastic in fetal life. Establishment of
      healthy neural functional systems during the fetal period is essential to normal
      growth and development. Across the last several decades, remarkable progress has
      been made in understanding the development of human fetal functional brain
      systems. This is largely due to advances in imaging methodologies. Fetal
      neuroimaging began in the 1950-1970's with fetal electroencephalography (EEG)
      applied during labor. Later, in the 1980's, magnetoencephalography (MEG) emerged
      as an effective approach for investigating fetal brain function. Most recently,
      functional magnetic resonance imaging (fMRI) has arisen as an additional powerful
      approach for examining fetal brain function. This review will discuss major
      developmental findings from fetal imaging studies such as the maturation of
      prenatal sensory system functions, functional hemispheric asymmetry, and sensory
      driven neurodevelopment. We describe how with improved imaging and analysis
      techniques, functional imaging of the fetus has the potential to assess the
      earliest point of neural maturation and provide insight into the patterning and
      sequence of normal and abnormal brain development. 

PMID- 23542739
TI  - Monitoring dendritic cell migration using 19F / 1H magnetic resonance imaging.
AB  - Continuous advancements in noninvasive imaging modalities such as magnetic
      resonance imaging (MRI) have greatly improved our ability to study physiological
      or pathological processes in living organisms. MRI is also proving to be a
      valuable tool for capturing transplanted cells in vivo. Initial cell labeling
      strategies for MRI made use of contrast agents that influence the MR relaxation
      times (T1, T2, T2*) and lead to an enhancement (T1) or depletion (T2*) of signal
      where labeled cells are present. T2* enhancement agents such as ultrasmall iron
      oxide agents (USPIO) have been employed to study cell migration and some have
      also been approved by the FDA for clinical application. A drawback of T2* agents
      is the difficulty to distinguish the signal extinction created by the labeled
      cells from other artifacts such as blood clots, micro bleeds or air bubbles. In
      this article, we describe an emerging technique for tracking cells in vivo that
      is based on labeling the cells with fluorine ((19)F)-rich particles. These
      particles are prepared by emulsifying perfluorocarbon (PFC) compounds and then
      used to label cells, which subsequently can be imaged by (19)F MRI. Important
      advantages of PFCs for cell tracking in vivo include (i) the absence of carbon
      bound (19)F in vivo, which then yields background-free images and complete cell
      selectivityand(ii) the possibility to quantify the cell signal by (19)F MR
      spectroscopy.

PMID- 23542740
TI  - Sensing and alarm function of resident memory CD8+ T cells.
AB  - CD8(+) T cells eliminate intracellular infections through two contact-dependent
      effector functions: cytolysis and secretion of antiviral cytokines. Here we
      identify the following additional function for memory CD8(+) T cells that persist
      at front-line sites of microbial exposure: to serve as local sensors of
      previously encountered antigens that precipitate innate-like alarm signals and
      draw circulating memory CD8(+) T cells into the tissue. When memory CD8(+) T
      cells residing in the female mouse reproductive tract encountered cognate
      antigen, they expressed interferon-gamma (IFN-gamma), potentiated robust local
      expression of inflammatory chemokines and induced rapid recruitment of
      circulating memory CD8(+) T cells. Anamnestic responses in front-line tissues are
      thus an integrated collaboration between front-line and circulating populations
      of memory CD8(+) T cells, and vaccines should establish both populations to
      maximize rapid responses.

PMID- 23542742
TI  - Proton-nitrogen-14 overtone two-dimensional correlation NMR spectroscopy of solid
      sample at very fast magic angle sample spinning.
AB  - (1)H-(14)N overtone (OT) heteronuclear multiple quantum coherence (HMQC)
      experiment at very fast magic angle spinning (MAS) is reported. The (14)N OT
      coherence is excited and reconverted by (14)N OT pulses at twice the (14)N Larmor
      frequency. The OT coherence is free from the first order quadrupolar broadening.
      MAS further removes the broadening due to chemical shift anisotropy (CSA). With a
      small 0.75 mm MAS rotor and coil system, very fast MAS up to 90 kHz and very
      strong rf field are achieved, enhancing the sensitivity of indirect (14)N OT
      observation via protons. In comparison with (1)H-(14)N double-quantum HMQC, an
      enhancement factor of 1.8 is obtained for glycine with the (14)N OT irradiation.
      The bandwidth in the (14)N OT dimension is limited due to long (14)N OT pulses.

PMID- 23542741
TI  - A combinatorial F box protein directed pathway controls TRAF adaptor stability to
      regulate inflammation.
AB  - Uncontrolled activation of tumor necrosis factor receptor-associated factor
      (TRAF) proteins may result in profound tissue injury by linking surface signals
      to cytokine release. Here we show that a ubiquitin E3 ligase component, Fbxo3,
      potently stimulates cytokine secretion from human inflammatory cells by
      destabilizing a sentinel TRAF inhibitor, Fbxl2. Fbxo3 and TRAF protein in
      circulation positively correlated with cytokine responses in subjects with
      sepsis, and we identified a polymorphism in human Fbxo3, with one variant being
      hypofunctional. A small-molecule inhibitor targeting Fbxo3 was sufficient to
      lessen severity of cytokine-driven inflammation in several mouse disease models.
      These studies identified a pathway of innate immunity that may be useful to
      detect subjects with altered immune responses during critical illness or provide
      a basis for therapeutic intervention targeting TRAF protein abundance.

PMID- 23542743
TI  - Signal intensities in 1H-13C CP and INEPT MAS NMR of liquid crystals.
AB  - Spectral editing with CP and INEPT in (13)C MAS NMR enables identification of
      rigid and mobile molecular segments in concentrated assemblies of surfactants,
      lipids, and/or proteins. In order to get stricter definitions of the terms
      "rigid" and "mobile", as well as resolving some ambiguities in the interpretation
      of CP and INEPT data, we have developed a theoretical model for calculating the
      CP and INEPT intensities as a function of rotational correlation time tauc and C
      H bond order parameter SCH, taking the effects of MAS into account. According to
      the model, the range of tauc can at typical experimental settings (5kHz MAS, 1ms
      ramped CP at 80-100kHz B1 fields) be divided into four regimes: fast (tauc<1ns),
      fast-intermediate (tauc~0.1MUs), intermediate (tauc~1MUs), and slow (tauc>0.1ms).
      In the fast regime, the CP and INEPT intensities are independent of tauc, but
      strongly dependent on |SCH|, with a cross-over from dominating INEPT to
      dominating CP at |SCH|>0.1. In the intermediate regime, neither CP nor INEPT
      yield signal on account of fast T1rho and T2 relaxation. In both the fast
      intermediate and slow regimes, there is exclusively CP signal. The theoretical
      predictions are tested by experiments on the glass-forming surfactant n-octyl
      beta-d-maltoside, for which tauc can be varied continuously in the nano- to
      millisecond range by changing the temperature and the hydration level. The
      atomistic details of the surfactant dynamics are investigated with MD
      simulations. Based on the theoretical model, we propose a procedure for
      calculating CP and INEPT intensities directly from MD simulation trajectories.
      While MD shows that there is a continuous gradient of tauc from the surfactant
      polar headgroup towards the methyl group at the end of the hydrocarbon chain,
      analysis of the experimental CP and INEPT data indicates that this gradient gets
      steeper with decreasing temperature and hydration level, eventually spanning four
      orders of magnitude at completely dry conditions.

PMID- 23542744
TI  - The prevalence and costs of defensive medicine among orthopaedic trauma surgeons:
      a national survey study.
AB  - OBJECTIVES: Defensive medicine includes medical practices that exonerate
      physicians from liability without benefit to patients. The national prevalence of
      defensive medicine in orthopaedic trauma surgery has not been investigated.
      METHODS: In September 2010, 2000 orthopaedic surgeons randomly chosen from the
      American Academy of Orthopaedic Surgeons registry received invitations to answer
      a survey on defensive medicine. Among these surgeons, 1214 (61%) completed the
      survey and 222 (18.5%) identified themselves as nonmilitary orthopaedic
      traumatologists. Cost analysis was performed using Centers for Medicare and
      Medicaid data at the 2011 current procedural terminology code level and then
      aggregated to reflect the 8 domains of care assessed. RESULTS: For orthopaedic
      traumatologists, on average 22% of all ordered tests were for defensive reasons
      (radiography, 19%; computed tomographic scanning, 23%; magnetic resonance
      imaging, 27%; ultrasound, 42%; referrals, 29%; laboratory tests, 23%; and
      biopsies, 16%). Defensive hospital admissions averaged 9% each month. Orthopaedic
      traumatologists reported fewer referrals to specialists compared with non-trauma
      orthopaedists (P = 0.02), with no significant difference in overall monthly
      defensive expenditures.Using 2011 current procedural terminology code
      reimbursement data, defensive medicine costs per respondent were calculated to be
      approximately $7800 monthly or $94,000/y, which is 20% of each physician's
      spending. Given the approximately 2724 orthopaedic trauma surgeons in practice in
      the United States according to the 2010 American Academy of Orthopaedic Surgeons
      Census, the national cost of defensive medicine for orthopaedic trauma surgery is
      estimated to be $256.3 million annually. CONCLUSIONS: Defensive medicine among
      orthopaedic trauma surgeons is a significant factor in health care costs and of
      marginal benefit to patients. Policies aimed at managing liability risk may be
      useful in containing such practices.

PMID- 23542745
TI  - Both bone forearm fractures in children and adolescents, which fixation strategy
      is superior - plates or nails? A systematic review and meta-analysis of
      observational studies.
AB  - OBJECTIVES: To determine which method of operative fixation, plate and screw, or
      intramedullary nails (IMN) fixation is superior for pediatric both bone forearm
      fractures (BBFF). DATA SOURCES: PubMed, EMBASE, and Cochrane, from 1980 to 2011,
      in English. STUDY SELECTION: We selected for detailed review all studies with
      children or adolescents with comparative data (or individual patient data) for
      BBFF fixed with IMN or open reduction internal fixation with plates and screws.
      Selected studies also required outcomes of interest including fracture union,
      complications, functional outcome, cosmesis, and the need for hardware removal.
      DATA EXTRACTION: Data were extracted from each study; publication bias was
      assessed using funnel plots and Egger statistic. Study quality was assessed using
      the standardized method described by Zaza et al. DATA SYNTHESIS: A DerSimonian
      and Laird random-effects model was used to assess differences between dichotomous
      variables. A continuity correction was applied in cases of zero events. A
      sensitivity analysis was performed with studies that separated out older children
      and adolescents. CONCLUSIONS: All studies identified were observational. IMN and
      plate and screw constructs are acceptable options in the fixation of pediatric
      BBFF. The literature fails to demonstrate a difference between IMN and plate and
      screw constructs. Outcomes were excellent in nearly 9 of 10 patients regardless
      of fixation strategy. Delayed unions and nonunions were rare and slightly more
      common in IMN, although the difference was not statistically significant. These
      results suggest that complication rates are similar, although the type of
      complication may vary. IMN provides improved cosmesis but, in general, requires a
      second operation to remove hardware.

PMID- 23542746
TI  - Evaluation of oxidative stress and genetic damage caused by detergents in the
      zebrafish Danio rerio (Cyprinidae).
AB  - Detergents are used in large quantities and some of their ingredients are highly
      toxic to aquatic organisms. In the present study the toxicity (lipid
      peroxidation) and genotoxic (frequency of DNA strand breaks) effects were
      evaluated in the gill and liver tissues of zebrafish (Danio rerio), exposed for
      16days to a sublethal concentration (CL10) of two commercial detergents (laundry
      and dishwasher use) and an anionic surfactant: alkyl lauryl sulfonate (LAS). The
      results demonstrated high toxicity with dishwasher detergent, resulting in high
      lipid peroxidation levels (MDA malondialdehyde evaluation). No differences in MDA
      concentrations were found among fish exposed to laundry detergent and organisms
      exposed to LAS. In the genetic damage evaluation, significant differences in the
      number of cells with DNA strand breaks (comets) were observed: the fish exposed
      to dishwasher detergent presented the highest number of damaged cells (79%), in
      comparison with those exposed to other products (laundry and LAS) and the control
      group (8% damaged cells). The toxicity of dishwasher detergent (biological
      detergent containing enzymes and perfume) was higher than the value observed with
      LAS. Laundry detergent does not contain enzymes or perfume and its toxicity was
      similar to LAS. Since detergents are complex mixtures of different substances, in
      which additive and/or synergistic effects may occur, the deleterious effect
      caused by the dishwasher detergent was probably due to the combined effects of
      the ingredients of detergent.

PMID- 23542747
TI  - In vitro response of putative fatty acid-sensing systems in rainbow trout liver
      to increased levels of oleate or octanoate.
AB  - In a previous study we provided evidence for the presence in liver of rainbow
      trout of fatty acid (FA) sensing systems responding to changes in levels of
      oleate (long-chain FA) or octanoate (medium-chain FA). Since those effects could
      be attributed to an indirect effect, we have evaluated in the present study in
      vitro (in the absence of extrahepatic regulatory mechanisms) whether or not liver
      responds to changes in FA concentration in a way similar to that previously
      observed in vivo. Accordingly, liver slices were exposed to increased oleate or
      octanoate concentrations to evaluate changes in parameters related to FA
      metabolism, FA transport, nuclear receptors and transcription factors, ROS
      effectors, and glucose metabolism. The responses observed in vitro in liver were
      in general not coincident with those previously observed in vivo allowing us to
      suggest that FA sensing capacity of liver in vivo is of indirect nature and could
      be related among other reasons to an interaction with other endocrine systems
      and/or to FA sensing in hypothalamus.

PMID- 23542748
TI  - Gene expression and biochemical responses in brain of zebrafish Danio rerio
      exposed to organic nanomaterials: carbon nanotubes (SWCNT) and fullerenol
      (C60(OH)18-22(OK4)).
AB  - Nanomaterials (NM) industry had grown in the last decade, although there are few
      studies concerning its potential toxicity effects on aquatic organisms. In this
      study the freshwater zebrafish (Danio rerio) was exposed to two kinds of carbon
      NM, single-wall carbon nanotubes (SWCNT) and fullerenol [C60(OH)18-22(OK4)] to
      analyze oxidative stress responses on fish brain. Adult zebrafish (mean mass:
      0.52+/-0.01g) were submitted to intraperitoneal injections of SWCNT suspension
      and fullerenol solution (30mg/kg of fish), receiving one or two doses with a time
      interval of 24h. Results showed that total antioxidant capacity was lowered in
      brains of fish exposed 24h to fullerenol when compared to those from SWCNT
      treatment (p<0.05). After 48h, fullerenol induced higher expression of both
      catalytic and regulatory subunits of enzyme glutamate cysteine ligase when
      compared to control group (p<0.05), indicating an antioxidant behavior. In vitro
      assays showed a dual effect of SWCNT, since a pro-oxidant behavior was observed
      at low concentrations (0.1 and 1.0mg/L) and an antioxidant one at the highest
      concentration (10.0mg/L). Few biological responses were altered by this NM:
      decrease in total antioxidant capacity and induction of the expression of the
      transcription factor Nrf2 when compared to control group.

PMID- 23542749
TI  - Combination of fenretinide and indole-3-carbinol results in synergistic cytotoxic
      activity inducing apoptosis against human breast cancer cells in vitro.
AB  - The outcome in patients with breast cancer is not satisfactory to date, although
      new chemotherapy regimens have been introduced in clinics. Therefore, novel
      approaches are required for better management of patients with breast cancer. In
      this study, we tested the cytotoxic activity of a new combination of fenretinide,
      a synthetic retinoid, with indole-3-carbinol, a natural product present in
      vegetables such as broccoli and cabbage, against MCF-7 (estrogen receptor
      positive) and MDA-MB-231 (estrogen receptor-negative) cell lines. It has been
      found that the combination resulted in more powerful cytotoxic activity, by
      induction of apoptosis, compared with that when they were used singly. In
      conclusion, this novel combination warrants in-vivo experiments to elucidate its
      possible use in the treatment of breast cancer.

PMID- 23542750
TI  - Neoadjuvant TPF in locally advanced head and neck cancer can be followed by
      radiotherapy combined with cisplatin or cetuximab: a study of 157 patients.
AB  - Neoadjuvant TPF (docetaxel, cisplatin, 5-fluorouracil), followed by radiotherapy
      or chemoradiotherapy with weekly carboplatin, increases overall survival and
      organ preservation. We assessed whether TPF could be used in routine practice and
      whether radiotherapy potentiated with cisplatin or cetuximab was feasible and
      could increase survival. We retrospectively reviewed 157 patients with advanced
      head and neck squamous cell carcinoma treated with TPF in four French
      institutions between May 2005 and March 2009. After induction, operable patients
      had undergone surgery and were irradiated, and potentiated in some cases with
      cetuximab or cisplatin. Most patients (79%) had been treated with organ
      preservation strategies. The two most common sites were the hypopharynx (34%) and
      the oropharynx (30%). The response rate to TPF was 84%, including 26% with a
      complete response. Radiotherapy had been provided to 144 (92%) patients (of whom
      17 had received radiotherapy alone, 46 had received q3w cisplatin, 30 had
      received q1w cisplatin, and 37 had received cetuximab). Potentiation had been
      achieved as planned in 59, 63, and 62% of patients treated with q3w cisplatin,
      q1w cisplatin, and cetuximab, respectively. After a median follow-up of 39.9
      months, the median overall survival was 43 months. No significant difference was
      observed in progression-free survival or overall survival according to the type
      of potentiation. This study confirms the efficacy and tolerability of TPF
      induction, followed by chemoradiation, with outcomes similar to those for
      patients irradiated without induction. The best potentiation of radiotherapy
      after induction has not yet been determined.

PMID- 23542751
TI  - Clinical activity of sorafenib in a previously treated advanced urothelial cancer
      patient.
AB  - A male patient, with advanced urothelial carcinoma, who had previously received
      cisplatin, was treated with sorafenib off-licence for 10.7 months. Evaluation of
      tumour response with computed tomography scans indicated a reduction in tumour
      size and necrosis of the metastases within 2 months. Progression-free survival
      was 10.5 months. Side effects were manageable and not beyond the National Cancer
      Institute Common Terminology Criteria for Adverse Events version 3.0 grade 2.
      Molecular profiling of two of the proposed targets of sorafenib, platelet-derived
      growth factor receptor beta and vascular endothelial growth factor receptor 2, of
      the patient's tumour lesion showed high and intermediate expression levels in the
      tumour as compared with the surrounding non-neoplastic tissue. In contrast to
      previous reports, we report a clinically meaningful effect of sorafenib in a
      patient with advanced urothelial carcinoma. Hence, it appears that a fraction of
      patients with this disease are sensitive to this compound. To identify
      subpopulations of responders, we propose that clinical trials evaluating
      sorafenib and other targeted drugs should be biomarker-driven and designed with
      endpoints that consider the mode of action of the specific compound.

PMID- 23542752
TI  - First assessment of whole-brain radiation therapy combined with pemetrexed-based
      chemotherapy in non-small-cell lung carcinoma: data on safety and efficacy.
AB  - The folate antimetabolite pemetrexed was approved for the treatment of patients
      with metastatic nonsquamous non-small-cell lung carcinoma. Its activity on brain
      metastases makes pemetrexed attractive in combination with whole-brain radiation
      therapy (WBRT), but it could also potentially increase toxicity. We examined the
      medical records of 43 consecutive patients with brain metastases from non-small
      cell lung carcinoma. Patients received pemetrexed-based chemotherapy at a dose of
      500 mg/m. The median total number of pemetrexed-based chemotherapy cycles was 4
      (range: 1-28). During the course of chemotherapy, patients received WBRT
      delivering 30 Gy in 10 fractions (n=34) or 20 Gy in five fractions (n=9). The
      median follow-up time was 30.5 weeks (range: 1-79 weeks). Intracranial
      progression was a cause of death in nine patients (20.9%). Clinical benefit of
      WBRT was reported in 30 patients (69.8%). The best radiological response was a
      complete response in eight patients (18.6%), a partial response in 16 patients
      (37.2%), stable disease in 11 patients (25.6%), and progression in four patients
      (9.3%). A stable intracranial disease until the last follow-up was observed in 26
      patients (60.5%). The median estimated overall survival was 31 weeks (95% CI: 24
      37 weeks). Most WBRT-related toxicities were low and 21 patients (48.9%) had no
      reported acute neurological toxicity. One patient developed unexplained
      encephalopathy 5 weeks after WBRT completion in the context of progressive
      diffuse brain metastases. The combination of pemetrexed with WBRT led to
      considerable clinical improvement and tumor responses in most patients. Overall
      neurological toxicity was rather low. A clinical trial is essential for better
      analysis of the potential synergistic effects of a drug with radiation and
      evaluation of neurological toxicity. 

PMID- 23542753
TI  - [Genericum? Which one should I choose?].

PMID- 23542754
TI  - Automated Neuropsychological Test Battery in depression -- preliminary data.
AB  - AIMS: Studies have demonstrated neuropsychological deficits across a variety of
      cognitive domains in patients with major depressive disorder (MDD) during acute
      episode. However, limited data are available concerning whether these
      abnormalities persist in the remission phase. METHODS: In the present study
      CANTAB (Cambridge Automated Neuropsychological Test Battery) was used to evaluate
      the cognitive impairment associated with depression during acute episode and in
      remission. 25 patients with MDD during an acute episode and 11 patients also
      during remission were tested with CANTAB. RESULTS: During the acute episode,
      Delayed matching to sample, Paired associate learning, Spatial recognition
      memory, Rapid visual processing and Visuospatial planning were impaired. In
      remission the improvement of visual learning ability, spatial recognition memory,
      psychomotor speed, and executive function was observed. CONCLUSIONS: The results
      suggest that MDD is associated with neurocognitive dysfunctions in different
      domains, the most prominent deficit was found in the Paired associate learning
      test, which requires both the elaboration of "frontal strategies" and the
      "mnemonic processes". Cognitive impairment was found to improve partly in
      remission, suggesting that an individual's current mood interacts with the
      ability to perform a cognitive task. Besides these state markers, trait deficits
      are important because cognitive impairments which do not improve in remission
      might serve as endophenotypes of depression.

PMID- 23542756
TI  - [Pulvinar].
AB  - The pulvinar is the largest nucleus of the thalamus. Its lateral and inferior
      areas have rich connections with the visual- and dorsolateral parietal cortices.
      Several cells in the medial and upper area connect the anterior cingulum and the
      premotor and prefrontal association areas. This neuronal network was considered
      to organize the saccades and visual attention. Other cells in the medial nucleus
      have axonal connections with paralimbic-, insular and higher order association
      cortices. The medial structure integrates complex sensory information with limbic
      reactivity settings, transmitting these to the temporal and parieto-occipital
      centres. The pulvinar is supplied by the posterior chorioideal artery. Visual
      salience is considered to be an important function of the pulvinar. Visual
      selection enables subjects to choose the actually adequate behavioral act. To
      serve the visual salience the pulvinar may also inhibit inappropriate eye
      movements. The pulvinar appears to be a key structure of the EEG's alpha rhythm
      generator, acting together with the parietooccipital and temporal cortices.
      Dynamic fluctuation of BOLD signals on fMRI correlates well with the change of
      alpha power even in resting state. We presume that the pulvinar is part of a
      closed cortico-subcortical circuit, analogous with the striatum, but the output
      of the pulvinar initiates complex behavioral reactions, including perception,
      selective attention and emotions. Damage of the pulvinar may elicit contralateral
      visual neglect, because of the dissociation of the neuronal network integrated by
      the superior temporal area. Increased activity of the pulvinar was found during
      abrupt reaction to fearful visual signals; and also in the etiopathology of
      endogenous depressions through the alteration of serotonin transporters.
      Increased bilateral signal intensity of the pulvinar on MRI was detected in cases
      of the new variants of Creutzfeldt-Jakob- and Fabry diseases.

PMID- 23542755
TI  - [New data for the pathomechanism of neuropathic pain: therapeutic evidences].
AB  - The present work is based on literature data from PubMed. Neuropathic pain is
      caused by a lesion or disease of the somatosensory system. Peripheral and central
      sensitization play a crucial role in its pathomechanism. The clinical symptoms
      are mainly characterized by burning and throbbing pain and sensory disturbances
      like hyperalgesia and allodynia. Therapeutic recommendations are antidepressants,
      antiepileptics, opioids and neuro-stimulation methods.

PMID- 23542757
TI  - The possibilities of suicide prevention in adolescents. A holistic approach to
      protective and risk factors.
AB  - There is no other such complex physical, biological, somatic, mental,
      psychological, psychiatric, cultural, social and spiritual phenomenon and general
      public health problem, so much unexplained, meaningless, so tragic, painful, and
      unreasonable, so difficult, contradictory and mystified like suicide. In spite of
      the several already identified background factors, we do not and we can not know
      the real reasons behind suicide, because suicide is multi-causal, and can never
      be traced back to one single cause, but there are always many biological,
      psychological-psychiatric, historical, social and cultural factors involved in
      its development. However, the strongest suicide risk factor is an unrecognized
      and untreated mental disorder. Suicide among young people is one of the most
      serious public health problems. In Hungary 1395 young people lost their lives due
      to suicide in the 24> age group between 2000-2010, 1150 males and 245 females.
      According to epidemiological studies, 24.7% of children and adolescents suffer
      from some form of behaviour-, conduct- or other psychiatric disorders. Among
      adolescents (aged 15-24) suicide was the first leading cause of death in 2010.
      Despite great advances in the psychopharmacology and psychotherapy of mental
      disorders, suicides persist as a major cause of mortality, especially among the
      15-24-year old population. Victims of suicide are not healthy individuals. They
      always suffer from psychiatric or mental, physical or somatic, cultural (social,
      historical, mythological) and spiritual disorders. The author tries to classify
      suicide protective and risk factors according to physical-biological, mental
      psychological, cultural-social, and spiritual aspects. However, it must be
      remembered that these factors are not necessarily present in each and every case
      and may vary from one country to another, one person to another, depending on
      cultural, political, (spiritual) and economical features. Risk and protective
      factors can occur (1) at the physical or biological-somatic level which includes
      physical circumstances, genetics, health, and diseases; (2) at the mental or
      psychological level, which includes mental health, self-esteem, and ability to
      deal with difficult circumstances, manage emotions, or cope with stress; (3) at
      the cultural level or the broader life environment, and this includes social,
      political, environmental, and economic factors that contribute to available
      options and quality of life; (4) at the social level, which includes
      relationships and involvement with others such as family, friends, workmates, the
      wider community and the person's sense of belonging; (5) at the spiritual level,
      which includes faith, hope, charity, despair, salvation. Children and adolescents
      spend a lot of time at school, so teachers must be educated to notice any warning
      signs of suicide, but the majority of pedagogues not only do not know the most
      important mental and psychosomatic symptoms, but do not recognize them in
      children and do not know how to handle them either. Hopelessness is the most
      important spiritual risk factor. The Beck Hopelessness Scale is a tool for easy
      application in general practice. The author lists some important symptoms and
      signs that neither parents nor teachers are able to recognize and handle, and
      provides useful advice for prevention.

PMID- 23542758
TI  - [Affective disorders and their treatment during pregnancy and after birth -- a
      review].
AB  - Treatment and management of affective disorders associated with pregnancy is
      still an underemphasized field receiving little attention, furthermore, it is
      burdened with misinformation as well as incomplete or missing knowledge.
      Professionals of related fields (psychiatrists, obstetrician-gynecologists) often
      provide patients with contradicting information or, due to their lack of
      sufficient knowledge, keep referring the patient for information between
      different services. However, there is an increasing amount of data and
      information available, suitable for drawing conclusions and making it possible to
      provide adequate and credible counselling and information for pregnant women or
      family planning couples. In the present paper we aim to facilitate this process
      by reviewing the currently available information.

PMID- 23542759
TI  - Extended release quetiapine fumarate and pregnancy.
AB  - We report on a case of a patient with schizophrenia who was taking 700 mg
      extended release quetiapine fumarate during her entire pregnancy to prevent
      relapse. At week 41 she gave birth to a healthy boy. The newborn's weight was
      3410 gramms, his height was 49 cm, his Apgar score in the first minute was 9, and
      at 5 minutes, it was 10.

PMID- 23542760
TI  - An unusual case of paratesticular mesothelioma on the site of previously excised
      epididymal adenomatoid tumour.
AB  - INTRODUCTION: Malignant paratesticular tumours are rare. We report a case of
      paratesticular malignant mesothelioma in a patient who had excision of an
      adenomatoid tumour on the same site in 2 occasions previously. PRESENTATION OF
      CASE: A middle aged man who had an adenomatoid tumour excised from his left
      hemiscrotum fifteen years previously was referred with a suspicious left
      epididymal lump. This was followed up sonographically for 2 years until it showed
      signs of enlargement and testicular invasion; it was then managed with radical
      orchidectomy. The histology showed paratesticular epithelioid malignant
      mesothelioma. The patient was referred to the Oncologists for further management.
      DISCUSSION: Paratesticular tumours are commonly benign. Scrotal ultrasonography
      is the preferred diagnostic imaging method. Paratesticular malignant
      mesotheliomas are very rare and appear to have poor prognosis. The optimal
      adjuvant treatment post radical orchidectomy is not established yet. In our case
      there is suggestion of possible malignant transformation from previous
      adenomatoid tumour. CONCLUSION: In recurrent paratesticular tumours the
      clinicians should question the possibility of malignant transformation and manage
      these cases accordingly.

PMID- 23542761
TI  - Thrombophilia - how far and how much to investigate?
AB  - Thrombohemorrhagic balance is maintained by complicated interactions between the
      coagulation and fibrinolytic system, platelets, and the vessel wall. Dr. Virchow
      provided approach for investigating and managing thrombotic disorders. He
      proposed stasis, vascular injury, and hypercoagulability as causes for
      thrombosis. In 1965, antithrombin deficiency was described. After two decades,
      protein C and protein S deficiencies, mutations of factor V Leiden, and factor II
      were described. If we distinguish patients at high risk and low risk of
      thrombosis, we can optimize therapeutic decisions. There is currently no evidence
      to say that laboratory abnormality should influence intensity of anticoagulation.
      In this article we reviewed the risk factors and need for thrombophilia screening
      in patients. Screening general population for thrombophilia is not justified or
      recommended at this time.

PMID- 23542762
TI  - A profile of carbohydrate metabolites in the fasting northern elephant seal.
AB  - Northern elephant seals endure prolonged periods of food deprivation at multiple
      life-history stages and simultaneous with energetically costly activities
      including reproduction and development. Most mammals decrease their energy
      expenditure while fasting, with simultaneous reductions in gluconeogenesis and
      circulating glucose concentration. Paradoxically, elephant seals maintain high
      rates of both energy expenditure and gluconeogenesis, and high blood glucose
      concentrations throughout fasting. We therefore characterized the suite of
      changes that occur in carbohydrate metabolites during fasting in northern
      elephant seals. Using a broad-based metabolomics platform we investigated fasting
      during two states-lactation in adult females and the post-weaning developmental
      period in pups. A total of 227 metabolites were detected in seal plasma; 31
      associated with carbohydrate metabolism were analyzed in the present study.
      Several compounds showed similar responses during lactation and the post-weaning
      fast (e.g. glycerol and mesaconate) whereas other compounds displayed quite
      different abundances between groups (e.g. citrate and pyruvate). This work found
      that, while the changes that occur with fasting were frequently similar in
      lactating females and developing pups, the relative abundance of compounds often
      varied markedly. These differences suggest that the metabolic strategies used to
      endure prolonged fasts are influenced by life-history or nutrient constraints.

PMID- 23542763
TI  - Radiation dose measurements for optimisation of chest X-ray examinations of
      children in general radiography hospitals.
AB  - This study was performed to measure the entrance surface air kerma (ESAK) for
      optimisation of chest X-ray examination of children in general radiography
      hospitals in Khartoum. ESAK was estimated using the X-ray tube output exposure
      and patient-specific exposure parameters collected during routine examinations.
      The estimated ESAK values per radiography ranged from 17 to 89 MUGy, 32 to 161,
      67 to 242, 77 to 278; and from 95 to 389 MUGy for Newborn, 1, 5, 10 and 15 y
      children, respectively. Doses are comparable with a previous study and are
      somewhat higher than the UK reference dose levels. The study demonstrated the
      necessity to follow guidelines for quality radiograph as a key element in the
      optimisation of X-ray examination of children. Frequent dose measurements are of
      particular importance for the optimisation of X-ray examination of children in
      general radiography hospitals. 

PMID- 23542764
TI  - External dose-rate conversion factors of radionuclides for air submersion, ground
      surface contamination and water immersion based on the new ICRP dosimetric
      setting.
AB  - For the assessment of external doses due to contaminated environment, the dose
      rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12)
      and FGR 13 have been widely used. Recently, there were significant changes in
      dosimetric models and parameters, which include the use of the Reference Male and
      Female Phantoms and the revised tissue weighting factors, as well as the updated
      decay data of radionuclides. In this study, the DCFs for effective and equivalent
      doses were calculated for three exposure settings: skyshine, groundshine and
      water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo
      simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy
      photons between 0.01 and 10 MeV. The transport calculations were performed for
      the source volume within the cut-off distances practically contributing to the
      dose rates, which were determined by a simplified calculation model. For small
      tissues for which the reduction of variances are difficult, the equivalent dose
      ratios to a larger tissue (with lower statistical errors) nearby were employed to
      make the calculation efficient. Empirical response functions relating photon
      energies, and the organ equivalent doses or the effective doses were then derived
      by the use of cubic-spline fitting of the resulting doses for 26 energy points.
      The DCFs for all radionuclides considered important were evaluated by combining
      the photon emission data of the radionuclide and the empirical response
      functions. Finally, contributions of accompanied beta particles to the skin
      equivalent doses and the effective doses were calculated separately and added to
      the DCFs. For radionuclides considered in this study, the new DCFs for the three
      exposure settings were within +/-10 % when compared with DCFs in FGR 13. 

PMID- 23542765
TI  - Age- and Gender-Specific Reference Intervals for Fasting Blood Glucose and Lipid
      Levels in School Children Measured With Abbott Architect c8000 Chemistry
      Analyzer.
AB  - Reference intervals for pubertal characteristics are influenced by genetic,
      geographic, dietary and socioeconomic factors. Therefore, the aim of this study
      was to establish age-specific reference intervals of glucose and lipid levels
      among local school children. This was cross-sectional study, conducted among
      Saudi school children. Fasting blood samples were collected from 2149 children,
      1138 (53%) boys and 1011 (47%) girls, aged 6 to 18 years old. Samples were
      analyzed on the Architect c8000 Chemistry System (Abbott Diagnostics, USA) for
      glucose, cholesterol, triglycerides, HDL and LDL. Reference intervals were
      established by nonparametric methods between the 2.5th and 97.5th percentiles.
      Significant differences were observed between boys and girls for cholesterol and
      triglycerides levels in all age groups (P < 0.02). Only at age 6-7 years and at
      adolescents, HDL and LDL levels were found to be significant (P < 0.001). No
      significant differences were seen in glucose levels except at age 12 to 13 years.
      Saudi children have comparable serum cholesterol levels than their Western
      counterparts. This may reflect changing dietary habits and increasing affluence
      in Saudi Arabia. Increased lipid screening is anticipated, and these reference
      intervals will aid in the early assessment of cardiovascular and diabetes risk in
      Saudi pediatric populations.

PMID- 23542766
TI  - The effect of smoking on the hearing status-a hospital based study.
AB  - BACKGROUND: Tobacco smoking has been known to affect the human physiology and
      among the various damaging effects of tobacco, it has been linked with its effect
      on the sense of hearing. AIM AND OBJECTIVE: This study was designed with the aim
      of finding the relationship between smoking and hearing loss in various age
      groups. MATERIALS AND METHODS: This study included 148 subjects among which 108
      were smokers and 40 were age matched non smokers. The smoking history of all the
      subjects whose ages ranged from 20 to 60 years was taken in detail and their
      audiometric thresholds were recorded in a sound proof room by a professional
      audiometrist. The data was analyzed by using appropriate statistical tests.
      OBSERVATION AND RESULTS: Smoking was found to be signifi- cantly associated with
      hearing loss. Also, the hearing loss was mainly of the sensorineural type, with
      the mild type (26-40 dB) of hearing loss being the most common among the smokers.

PMID- 23542767
TI  - Peripheral insensate neuropathy-is height a risk factor?
AB  - INTRODUCTION: Peripheral insensate neuropathy is one of the most commonest and
      the earliest forms of peripheral neuropathy. It is one of the leading causes of
      the disability in working population who are at risk. METHODS: A study was
      conducted in Kasturba medical college (Manipal university) in the year 2009-12,
      which included examination of 818 people of more than 30yrs of age by random
      sampling method who were attending the outpatient clinic. A monofilament was used
      to determine the peripheral insensate neuropathy, which was defined by the
      presence of one or more insensate areas. RESULTS: In our study , the prevalence
      of peripheral insensate neuropathy was 16.2 % ( p-0.0001), among which 9.7% were
      males and 7.5% were females. The males were 1.27 times significantly at a higher
      risk than the females , even after a height adjustment to the gender difference
      in height. As the height increased, the prevalence of peripheral insensate
      neuropathy increased, irrespective of the diabetic and hypertensive statuses. The
      risk of the peripheral insensate neuropathy increases at a height of >167 cm in
      males and at a height of >159 cm in females. CONCLUSION: The authors conclude
      that body height is an important and an independent risk factor for peripheral
      insensate neuropathy, irrespective of co morbidities. Height as a marker, helps
      the health care professionals in identifying the people who are at risk for
      peripheral insensate neuropathy.

PMID- 23542768
TI  - Occurrence of Laemobothrion maximum in Greater Coucal.
AB  - External examination of free range abandoned dead Greater Coucal in a veterinary
      dispensary, Vellore, Tamil Nadu, India revealed presence of a large sized louse
      in the feathers and was identified as Laemobothrion maximum on the basis of
      morphology and size of the louse.

PMID- 23542769
TI  - Gynecological Morbidity Among Grass-root Level Health Care Providers in an Urban
      Setup.
AB  - OBJECTIVES: The study of health status of grass-root level health care providers
      may help us understand the delivery gaps from the programmatic point of view.
      METHODS: A detailed interview of 313 Anganwadi workers (AWW) was taken in a
      predesigned, pretested questionnaire, and their clinical examination and Pap
      smear study were arranged at New Civil Hospital, Surat during November 2007-April
      2008. All AWWs were accompanied for follow up and examination. Data were analyzed
      using Epi-Info Software. RESULTS: Mean age of menarche and menopause was 14.3 and
      44 years, respectively. Among 73 women having menopause, 53 (72. 6%) had natural
      menopause. On taking history, only 9.5 % gave positive findings, while 42.3 % had
      positive clinical signs on examination. Inflammation was reported in 43.4 % Pap
      smear, while 2.8 % had cervical dysplasia of varying grades. CONCLUSIONS: All
      women should be advised to undergo complete pelvic examination including Pap
      Smear for the detection of gynecological morbidity.

PMID- 23542770
TI  - Extra-hepatic fascioliasis with peritoneal malignancy tumor feature.
AB  - Fascioliasis is a zoonose parasitic disease caused by Fasciola hepatica and
      Fasciola gigantica and is widespread in most regions of the world. Ectopic
      fascioliasis usually caused by juvenile Fasciola spp., but in recent years a few
      cases of tissue-embedded ova have been reported from different endemic areas. A
      79-year-old Iranian man resident in Eird-e-Mousa village from Ardabil Province,
      north-west of Iran, complained with abdominal pain, nausea, and intestinal
      obstruction symptoms referred to Ardabil Fatemi hospital. In laparotomy multiple
      intestinal masses with peritoneal seeding resembling of a malignant lesion were
      seen. After appendectomy and peritoneal mass biopsy with numerous intraperitoneal
      adenopathy, paraffin embedded blocks were prepared from each tissues. A blood
      sample was taken from the patient 5 months later for serological diagnosis.
      Histopathological examination of sections showed fibrofatty stroma with dense
      mixed inflammatory cells infiltration and fibrosis in peritoneal masses. Large
      numbers of ova of Fasciola spp. were noted with typical circumscribed granulomas.
      Despite of anti-fasciola treatment, IHA test for detecting anti F. hepatica
      antibodies was positive 5 months after surgery with a titer of 1/128. Due to
      multiple clinical manifestation of extra-hepatic fascioliasis, its differential
      diagnosis from intraperitoneal tumors or other similar diseases should be
      considered.

PMID- 23542771
TI  - Non-coding transcription at cis-regulatory elements: computational and
      experimental approaches.
AB  - Mammalian genomes are pervasively transcribed, generating mostly RNAs with no
      coding potential that display different size, structure and interspecies sequence
      conservation. A prominent contribution to the ncRNA pool comes from the
      transcription of cis-regulatory elements, namely promoters, enhancers and locus
      control regions. While this phenomenon has been extensively documented, possible
      roles of such ncRNAs in gene regulation are still unclear. Addressing this issue
      will require experimental strategies dealing with the low abundance of enhancer
      templated ncRNAs and aimed at specifically dissecting the relative role of
      transcription per se vs. RNA products. In this review, we first focus on the
      identification and characterization of cis-regulatory elements, highlighting the
      differences between emerging classes of ncRNAs associated to specific chromatin
      signatures. We then discuss current experimental strategies to dissect the
      function of nc transcription and computational approaches to the analysis and
      classification of regulatory sequences identified in next-generation sequencing
      experiments.

PMID- 23542772
TI  - Inherited polyneuropathies.
AB  - The large degree of clinical heterogeneity within each of the major categories of
      inherited neuropathies can lead to difficulties in making correct diagnoses based
      on clinical findings alone. The observation of key clinical findings coupled with
      electrophysiological findings and understanding of inheritance patterns, should
      allow the clinician to make judicious use of genetic testing to confirm the
      clinical diagnosis. An understanding of the clinical and electrophysiological
      nature of these disorders, as well as an understanding of how to clinically
      distinguish the inherited conditions from acquired conditions, is imperative to
      this process.

PMID- 23542773
TI  - Electrodiagnostic evaluation of carpal tunnel syndrome and ulnar neuropathies.
AB  - Carpal tunnel syndrome (CTS) and ulnar mononeuropathies at the elbow and wrist
      are the most common nerve entrapments in the upper extremities. Electrodiagnostic
      studies are a valid and reliable means of confirming the clinical diagnosis. This
      review addresses various electrodiagnostic techniques to evaluate the median and
      ulnar nerves at the wrist and elbow. It also discusses the limitations of
      electrodiagnostic studies with regard to the sensitivity and specificity of such
      testing.

PMID- 23542774
TI  - Entrapment neuropathies of the lower extremity.
AB  - Neuropathies that affect the lower limbs are often encountered after trauma or
      iatrogenic injury or by entrapment at areas of anatomic restriction. Symptoms may
      initially be masked by concomitant trauma or recovery from surgical procedures.
      The nerves that serve the lower extremities arise from the lumbosacral plexus,
      formed by the L2-S2 nerve roots. The major nerves that supply the lower
      extremities are the femoral, obturator, lateral femoral cutaneous, and the
      peroneal (fibular) and tibial, which arise from the sciatic nerve, and the
      superior and inferior gluteal nerves. An understanding of the motor and sensory
      functions of these nerves is critical in recognizing and localizing nerve injury.
      Electrodiagnostic studies are an important diagnostic tool. A well-designed
      electromyography study can help confirm and localize a nerve lesion, assess
      severity, and evaluate for other peripheral nerve lesions, such as plexopathy or
      radiculopathy.

PMID- 23542775
TI  - Electrodiagnostics and clinical correlates in acquired polyneuropathies.
AB  - Peripheral neuropathies result from a variety of inherited and acquired
      pathologies. They display an assortment of clinical signs and symptoms and
      present with a broad range of severity. Electrodiagnosis can play a key role in
      the evaluation of a suspected peripheral neuropathy. A peripheral nerve disorder
      is first suspected on the basis of history and physical examination findings.
      Electrodiagnosis is then used to confirm the diagnosis and to characterize the
      peripheral neuropathy, providing information about its distribution,
      pathophysiologic process (demyelinating vs axonal), and chronicity.

PMID- 23542776
TI  - The effects of combined trunk and gluteal neuromuscular electrical stimulation on
      posture and tissue health in spinal cord injury.
AB  - OBJECTIVE: To investigate whether combined trunk and gluteal neuromuscular
      electrical stimulation (NMES) alters seated posture and improves pelvic tissue
      health in persons with a spinal cord injury. DESIGN: Intervention study; case
      series. SETTING: Research laboratory, medical center. PARTICIPANTS: Seven persons
      with spinal cord injury recruited from a group of experienced implanted lower
      extremity NMES system users. INTERVENTION: Combined trunk and gluteal NMES in the
      sitting position. Five minutes of preintervention sitting was assessed, followed
      by 5 minutes of NMES application, and then 5 minutes of postintervention. MAIN
      OUTCOME MEASURES: Pelvic tissue health was evaluated by concurrently measuring
      transcutaneous oxygen tension (TcPO2) bilaterally over the ischia and the seating
      interface pressure (IP). TcPO2 data were binned into low (<10 mm Hg), medium (10
      30 mm Hg), and high (>30 mm Hg) ranges, and the percentage time that TcPO2 was in
      each range was calculated. Ischial and sacral regions of interest were defined
      and the maximum region of interest and mean IP were determined, together with the
      maximum IP gradient for the entire contact area. Initial seating postures varied;
      4 persons were initially sacral sitters. Tissue health responses to NMES were
      reviewed for sacral and nonsacral sitters. RESULTS: For sacral sitters, the
      sacral region IP and the maximum IP gradient tended to decrease during NMES and
      increased again after the intervention. Mean ischial TcPO2 increased during NMES
      and remained elevated after the intervention, increasing high TcPO2 percentage
      time for 50% of the sacral sitters both during and after the intervention.
      Nonsacral sitters showed few changes in tissue health as the result of the
      application of NMES. CONCLUSIONS: Trunk and gluteal stimulation acutely corrects
      anterior/posterior IP distribution, improving regional tissue health for sacral
      sitters. This correction requires constant application of NMES. The potential for
      positive changes in tissue health would be maximized by regular NMES use
      incorporating weight shifting.

PMID- 23542777
TI  - Reciprocal interactions between endothelial cells and macrophages in angiogenic
      vascular niches.
AB  - The ability of macrophages to promote vascular growth has been associated with
      the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A
      and proteases). More recently, a series of studies have also revealed that
      physical contact of macrophages with growing blood vessels coordinates vascular
      fusion of emerging sprouts. Interestingly, the interactions between macrophages
      and vascular endothelial cells (ECs) appear to be bidirectional, such that
      activated ECs also support the expansion and differentiation of proangiogenic
      macrophages from myeloid progenitors. Here, we discuss recent findings suggesting
      that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors,
      where sprouting blood vessels and immature myeloid cells like monocytes engage in
      heterotypic interactions that are required for angiogenesis. Finally, we provide
      an account of emerging mechanisms of cell-to-cell communication that rely on
      secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid
      exchange of molecules and genetic information between macrophages and ECs engaged
      in angiogenesis. 

PMID- 23542778
TI  - Molecular cloning, expression, and hormonal regulation of the chicken microsomal
      triglyceride transfer protein.
AB  - During an egg-laying cycle, oviparous animals transfer massive amounts of
      triglycerides, the major lipid component of very low density lipoprotein (VLDL),
      from the liver to the developing oocytes. A major stimulus for this process is
      the rise in estrogen associated with the onset of an egg-laying cycle. In
      mammals, the microsomal triglyceride transfer protein (MTP) is required for VLDL
      assembly and secretion. To enable studies to determine if MTP plays a role in
      basal and estrogen-stimulated VLDL assembly and secretion in an oviparous
      vertebrate, we have cloned and sequenced the chicken MTP cDNA. This cDNA encodes
      a protein of 893 amino acids with an N-terminal signal sequence. The primary
      sequence of chicken MTP is, on average, 65% identical to that of mammalian
      homologs, and 23% identical to the Drosophila melanogaster protein. We have
      obtained a clone of chicken embryo fibroblast cells that stably express the avian
      MTP cDNA and show that these cells display MTP activity as measured by the
      transfer of a fluorescently labeled neutral lipid. As in mammals, chicken MTP is
      localized to the endoplasmic reticulum as revealed by indirect immunofluorescence
      and by the fact that its N-linked oligosaccharide moiety remains sensitive to
      endoglycosidase H. Endogenous, enzymatically active MTP is also expressed in an
      estrogen receptor-expressing chicken hepatoma cell line that secretes
      apolipoprotein B-containing lipoproteins. In this cell line and in vivo, the
      expression and activity of MTP are not influenced by estrogen. Therefore, up
      regulation of MTP in the liver is not required for the increased VLDL assembly
      during egg production in the chicken. This indicates that MTP is not rate
      limiting, even for the massive estrogen-induced secretion of VLDL accompanying an
      egg-laying cycle.

PMID- 23542779
TI  - Heavy metal response of the heat shock protein 70 gene is mediated by duplicated
      heat shock elements and heat shock factor 1.
AB  - Heavy metals induce transcription of a number of mammalian genes, but in most
      cases the mechanism of induction has not been well characterized. The human heat
      shock protein 70 gene (hsp70) is activated by several heavy metals such as Cd and
      Zn, and the heat shock element (HSE) has been proposed to mediate metal response
      by previous studies. However, it was observed that the lack of further upstream
      sequences rendered the hsp70 promoter unresponsive to metals. A detailed deletion
      analysis of the promoter revealed that the distal HSE-like sequence (dHSE) is
      required for heavy metal response. A supershift assay showed that the heat shock
      factor 1 (HSF1) recognized dHSE, as well as the proximal HSE (pHSE). An hsp70
      promoter variant with a dHSE mutation that blocks HSF1 binding completely lost
      metal response, demonstrating that the HSF1/dHSE interaction is crucial. Another
      promoter variant with a similar pHSE mutation partially lost metal response,
      indicating that both HSEs are required for full activity. Knockdown of HSF1
      dramatically reduced the metal response of hsp70, demonstrating its essential
      role. Furthermore, a reporter gene regulated by the human hsp70 promoter, which
      lacked metal response in HSF1-null mouse cells, acquired the response upon over
      expression of a recombinant human HSF1. These results demonstrate that the
      duplicated HSEs and HSF1 constitute the mechanism for the heavy metal response of
      hsp70, which is distinct from the known metal regulatory system for the
      metallothionein genes.

PMID- 23542780
TI  - A functional polymorphism in interleukin-1alpha (IL1A) gene is associated with
      risk of alopecia areata in Chinese populations.
AB  - Alopecia areata (AA) is an inflammatory hair loss disorder with a major genetic
      component, which may cause great psychosocial distress for those affected.
      Studies have shown that interleukin-1 (IL-1) is a very potent inducer of hair
      loss and a significant human hair growth inhibitor. The 4-bp insertion/deletion
      (Indel) polymorphism (rs3783553) within the 3' untranslated regions of IL1A gene
      has been suggested to be associated with risk of various types of cancers,
      possibly through regulating expression of IL-1alpha levels. In the current study,
      we estimated the susceptibility to AA associated with rs3783553 in two
      independent case-control panels of Eastern and Southern Chinese populations,
      totally containing 313 AA cases and 626 healthy controls. Logistic regression
      analysis showed that the heterozygote and the homozygote 4-bp ins/ins confer a
      significantly lower risk of AA in both panels and total subjects [odds ratio
      (OR)=0.55, 95% confidence interval (C.I.)=0.41-0.75, P=6.24*10(-5); OR=0.47, 95%
      C.I.=0.28-0.76, P=0.001, respectively]. Stratification analysis based on age
      onset showed that the protective roles of ins/del and ins/ins genotype against
      developing AA was more obvious in AA patients with early age onset (<30years)
      under dominant model (OR=0.48, 95% C.I.=0.29-0.77, P=0.001). The results of
      luciferase assay showed that rs3783553 could influence expression of IL-1alpha in
      a miR-122 dependant manner. Taken together, our results suggested that the IL1A 4
      bp indel polymorphism may be a marker for genetic susceptibility to patchy (mild)
      AA in Chinese populations, likely through miR-122 mediated regulation.

PMID- 23542781
TI  - DAXX silencing suppresses mouse ovarian surface epithelial cell growth by
      inducing senescence and DNA damage.
AB  - Mouse ovarian surface epithelium (OSE) is a single layer of cubodial epithelial
      cells that covers the ovary surface and is involved in regulating the secretion
      and transport of 17beta-hydroxysteroid dehydrogenase. Recently, OSE cells have
      attracted particular interest as a major source of ovarian cancer. Death
      associated protein DAXX along with PML (promyelocytic leukemia protein) nuclear
      bodies (PML-NBs) reportedly play roles in transcriptional regulation and
      apoptosis. However, little is known regarding a role for DAXX in mOSE cells. In
      this study, we both over-expressed DAXX and depleted DAXX in primary mOSE cells.
      We found that Daxx deletion accelerated senescence in a p53/p21-dependent manner
      and promoted DNA damage by interacting with PML bodies without affecting cell
      cycle progression. These results suggest that DAXX may transform mOSE cells to an
      ovarian oncogenic phenotype and may be an anti-cancer target. 

PMID- 23542782
TI  - Usefulness of IgM-specific enzyme immunoassays for serodiagnosis of syphilis:
      comparative evaluation of three different assays.
AB  - OBJECTIVES: IgM antibodies are usually the first to be produced during treponemal
      infection. Three commercially available enzyme immunoassays (EIA) for detection
      of IgM antibodies against Treponema pallidum were evaluated. METHODS: Results of
      the Anti-Treponema-pallidum-ELISA (IgM; Euroimmun), Pathozyme Syphilis M Capture
      (Omega Diagnostics) and recomWell Treponema IgM (Mikrogen) were compared with
      those of the T. pallidum particle agglutination (TPPA) and the Venereal Disease
      Research Laboratory (VDRL) tests for 307 serum samples. RESULTS: The overall
      sensitivity (95% confidence interval [CI]) of the TPPA was 100% (97.7-100%)
      compared to 83.3% (76.5-88.8%) of the VDRL, 88.5% (82.4-93.0%) of the Pathozyme,
      84.6% (78.0-89.9) of the Euroimmun, and 73.6% (66.1-80.4%) of a modified
      recomWell test procedure. Specificities were in the range of 91.4-100%. In
      primary syphilis, sensitivities of the Pathozyme (89.8%; 95% CI, 79.2-96.2%) and
      Euroimmun tests (81.4%; 95% CI, 69.1-90.3%) were significantly higher (p < 0.05)
      than the sensitivity of the VDRL test (61%; 95% CI, 47.4-73.5%). IgM EIAs even
      were positive in some cases of suspected very early infection where the VDRL was
      non-reactive and the TPPA was indeterminate. CONCLUSIONS: In cases of suspected
      early infection specific IgM EIAs should be used in addition to other screening
      tests. The VDRL is not recommended for screening.

PMID- 23542783
TI  - Pegylated interferon plus ribavirin is suboptimal in IL28B CC carriers without
      rapid response.
AB  - OBJECTIVE: Some experts consider that hepatitis C virus (HCV) genotype 1-infected
      patients harboring IL28B genotype CC should be treated with interferon (Peg-IFN)
      plus ribavirin (RBV). This study aimed to assess the rate of sustained
      virological response (SVR) in these subjects, according to whether they achieve
      rapid virological response (RVR) or not. METHODS: Prospective cohort study
      conducted at the Infectious Diseases Units of three Spanish hospitals. 220
      treatment-naive, HCV genotype 1-infected patients, 160 of them HIV/HCV
      coinfected, who initiated dual therapy with peg-IFN plus RBV were analyzed in an
      on-treatment approach. RESULTS: 29 (18%) HIV/HCV-coinfected and 14 (23%) HCV
      monoinfected (p = 0.44) individuals developed RVR. In the overall population, 32
      (39%) patients with IL28B genotype CC versus 11 (8%) bearing genotype non-CC
      achieved RVR (p < 0.0001). In HCV-monoinfected patients with IL28B genotype CC,
      SVR was observed in 12 (92%) of those who achieved RVR and in 3 (30%) of those
      who did not (p = 0.0018). The corresponding figures for HIV/HCV-coinfected
      individuals were 19 (100%) and 14 (35%), respectively (p < 0.0001). CONCLUSION:
      Treatment-naive HCV-genotype 1-infected patients bearing favorable IL28B genotype
      should not be treated with dual therapy including Peg-IFN plus RBV if they do not
      achieve RVR. These subjects clearly represent candidates for more effective
      therapy with direct-acting antivirals. SUMMARY: Some experts consider that
      hepatitis C virus (HCV) genotype 1-infected patients harboring the favorable
      IL28B genotype CC should be treated with interferon plus ribavirin. However,
      patients harboring favorable IL28B genotype should not be considered likely
      responders to the same extent. This prospective cohort study conducted in 220
      treatment-naive HCV-infected patients with or without HIV coinfection patients
      shows that among the IL28B CC carriers, while the subset of those patients who
      achieve negative plasma HCV-RNA after 4 weeks (rapid virological response, RVR)
      of dual therapy have a rate of sustained virological response near to 100%, those
      who do not present RVR show a response rate lower than 40%. Therefore, treatment
      naive HCV-genotype 1-infected patients bearing favorable IL28B genotype who do
      not achieve RVR should be considered candidates for more effective therapy with
      direct-acting antivirals like boceprevir or telaprevir.

PMID- 23542784
TI  - Enteroviruses as major cause of microbiologically unexplained acute respiratory
      tract infections in hospitalized pediatric patients.
AB  - OBJECTIVE: To assess the etiological role and the clinical characteristics of HRV
      and HEV infections in pediatric patients hospitalized for acute respiratory tract
      infections (ARTIs). METHODS: RT-qPCR assays and molecular sequencing methods were
      used to identify HRV and HEV strains in nasopharyngeal aspirates of 309
      hospitalized pediatric patients with microbiologically unexplained ARTIs and in
      210 hospitalized pediatric patients without respiratory symptoms from September
      2009 to June 2010 in France. RESULTS: Among the 309 ARTI cases, 15 HEV and 172
      HRV strains were identified whereas only 1 HEV and 37 HRV strains were observed
      in control patients (187 vs. 38: P < 10(-3)). HRV strains were identified in 150
      of the 164 lower ARTIs whereas HEV strains were identified in only 14 of these
      cases. Among bronchiolitis and asthma exacerbation cases (n = 133), HEV infected
      cases were older (Median age (months) 36 vs. 11, P = 0.003) and were more
      frequently associated with a respiratory distress (P = 0.01) and a need for
      oxygen supply at the time of admission (P = 0.01) than cases infected by HRV
      strains. CONCLUSION: HRV and HEV strains were identified as potential etiological
      causes of 60.5% of microbiologically unexplained ARTIs diagnosed in hospitalized
      pediatric cases. A higher clinical severity was observed in HEV infected
      bronchiolitis or asthma exacerbation cases in comparison to HRV infected cases.

PMID- 23542785
TI  - High prevalence of renal dysfunction and association with risk of death amongst
      HIV-infected Ghanaians.
AB  - OBJECTIVES: To determine the prevalence of HIV-associated renal dysfunction (RD),
      identify risk factors for RD and explore the association between baseline renal
      function and mortality in an HIV-infected population in Ghana. METHODS:
      Creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) was
      calculated in patients attending an HIV clinic between 2004 and 2011 using
      Cockcroft-Gault, MDRD and CKD-EPI formulae. Logistic regression analysis was used
      to identify risk factors associated with RD and Kaplan-Meier/Cox proportional
      regression analyses to explore associations between baseline CrCl/eGFR and
      subsequent mortality. RESULTS: In 3137 patients starting antiretroviral therapy
      (ART) the frequency (95%-CI) of RD, defined by CrCl <60 ml/min/1.73 m(2) using
      Cockroft-Gault formula was 38.8% (37.1-40.5%). RD prevalence in a sub-population
      of 238 patients, including proteinuria in the definition, was 15.3% (10.3-22.1%)
      in ART-treated and 43.6% (34.0-53.7%) in ART-naive patients. RD at baseline was
      associated with increasing age, low CD4 counts, advanced WHO stage and female
      gender. Cox proportional hazard analysis identified an increased hazard of death
      with decreasing CrCl, HR 1.46 (1.31-1.63) for each tertile lower than CrCl of 90
      ml/min/1.73 m(2). CONCLUSIONS: RD is very common in HIV-infected ART-naive
      Ghanaians, and associated with increased risk of mortality. Screening and
      monitoring of RD is important in this setting, particularly as tenofovir use
      increases.

PMID- 23542786
TI  - PPARbeta/delta governs Wnt signaling and bone turnover.
AB  - Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and
      central regulators of fat and glucose homeostasis. Furthermore, PPARgamma has
      been implicated as major catabolic regulator of bone mass in mice and humans.
      However, a potential involvement of other PPAR subtypes in the regulation of bone
      homeostasis has remained elusive. Here we report a previously unrecognized role
      of PPARbeta/delta as a key regulator of bone turnover and the crosstalk between
      osteoblasts and osteoclasts. In contrast to activation of PPARgamma, activation
      of PPARbeta/delta amplified Wnt-dependent and beta-catenin-dependent signaling
      and gene expression in osteoblasts, resulting in increased expression of
      osteoprotegerin (OPG) and attenuation of osteoblast-mediated osteoclastogenesis.
      Accordingly, PPARbeta/delta-deficient mice had lower Wnt signaling activity,
      lower serum concentrations of OPG, higher numbers of osteoclasts and osteopenia.
      Pharmacological activation of PPARbeta/delta in a mouse model of postmenopausal
      osteoporosis led to normalization of the altered ratio of tumor necrosis factor
      superfamily, member 11 (RANKL, also called TNFSF11) to OPG, a rebalancing of bone
      turnover and the restoration of normal bone density. Our findings identify
      PPARbeta/delta as a promising target for an alternative approach in the treatment
      of osteoporosis and related diseases.

PMID- 23542787
TI  - Targeting the endocannabinoid system in the treatment of fragile X syndrome.
AB  - Fragile X syndrome (FXS), the most common monogenic cause of inherited
      intellectual disability and autism, is caused by the silencing of the FMR1 gene,
      leading to the loss of fragile X mental retardation protein (FMRP), a
      synaptically expressed RNA-binding protein regulating translation. The Fmr1
      knockout model recapitulates the main traits of the disease. Uncontrolled
      activity of metabotropic glutamate receptor 5 (mGluR5) and mammalian target of
      rapamycin (mTOR) signaling seem crucial in the pathology of this disease. The
      endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive
      performance, anxiety, nociception and seizure susceptibility, all of which are
      affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are
      activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term
      regulation of synaptic strength, as a consequence of mGluR5 activation, is
      altered in several brain areas of Fmr1 knockout mice. We found that CB1R blockade
      in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic
      approaches normalized cognitive impairment, nociceptive desensitization,
      susceptibility to audiogenic seizures, overactivated mTOR signaling and altered
      spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic
      like behavior. Some of these traits were also reversed by pharmacological
      inhibition of mTOR or mGluR5. Thus, blockade of ECS is a potential therapeutic
      approach to normalize specific alterations in FXS.

PMID- 23542789
TI  - Generation of aligned functional myocardial tissue through microcontact printing.
AB  - Advanced heart failure represents a major unmet clinical challenge, arising from
      the loss of viable and/or fully functional cardiac muscle cells. Despite optimum
      drug therapy, heart failure represents a leading cause of mortality and morbidity
      in the developed world. A major challenge in drug development is the
      identification of cellular assays that accurately recapitulate normal and
      diseased human myocardial physiology in vitro. Likewise, the major challenges in
      regenerative cardiac biology revolve around the identification and isolation of
      patient-specific cardiac progenitors in clinically relevant quantities. These
      cells have to then be assembled into functional tissue that resembles the native
      heart tissue architecture. Microcontact printing allows for the creation of
      precise micropatterned protein shapes that resemble structural organization of
      the heart, thus providing geometric cues to control cell adhesion spatially.
      Herein we describe our approach for the isolation of highly purified myocardial
      cells from pluripotent stem cells differentiating in vitro, the generation of
      cell growth surfaces micropatterned with extracellular matrix proteins, and the
      assembly of the stem cell-derived cardiac muscle cells into anisotropic
      myocardial tissue.

PMID- 23542788
TI  - GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to
      control of blood pressure.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) agonists exert antihypertensive actions
      through incompletely understood mechanisms. Here we demonstrate that cardiac
      Glp1r expression is localized to cardiac atria and that GLP-1R activation
      promotes the secretion of atrial natriuretic peptide (ANP) and a reduction of
      blood pressure. Consistent with an indirect ANP-dependent mechanism for the
      antihypertensive effects of GLP-1R activation, the GLP-1R agonist liraglutide did
      not directly increase the amount of cyclic GMP (cGMP) or relax preconstricted
      aortic rings; however, conditioned medium from liraglutide-treated hearts relaxed
      aortic rings in an endothelium-independent, GLP-1R-dependent manner. Liraglutide
      did not induce ANP secretion, vasorelaxation or lower blood pressure in Glp1r(-/
      ) or Nppa(-/-) mice. Cardiomyocyte GLP-1R activation promoted the translocation
      of the Rap guanine nucleotide exchange factor Epac2 (also known as Rapgef4) to
      the membrane, whereas Epac2 deficiency eliminated GLP-1R-dependent stimulation of
      ANP secretion. Plasma ANP concentrations were increased after refeeding in wild
      type but not Glp1r(-/-) mice, and liraglutide increased urine sodium excretion in
      wild-type but not Nppa(-/-) mice. These findings define a gut-heart GLP-1R
      dependent and ANP-dependent axis that regulates blood pressure.

PMID- 23542791
TI  - [The recent trend for neuroanesthesia].

PMID- 23542790
TI  - Factitious Biochemical Reports which are Caused Due to Paraproteinaemia in
      Multiple Myeloma - A Case Report.
AB  - Factitious biochemical reports result in the misguiding of clinicians,
      unnecessary retesting, wrong diagnoses and incorrect treatments. A vigilant
      biochemist identifies these factitious biochemical reports and alerts the
      clinician regarding the proper interpretation of the biochemical reports, thus
      preventing a misdiagnosis and an incorrect treatment. We are presenting a case
      report of a multiple myeloma patient who presented with factitious biochemical
      reports which were caused due to paraproteinaemia. In the present case, the
      patient presented with an underestimation of urea and creatinine, an
      underestimation of sodium, low albumin levels and high phosphate levels. On
      repeating the same tests after dilutions and deproteinizing, the effects of the
      paraproteins on the above mentioned tests were reduced. Thus, from the
      observations of our study, we suggest that the interference by paraproteinaemia
      can be reduced by analyzing the biochemical parameters after dilution and
      deproteinization.

PMID- 23542792
TI  - [Clinical features of unruptured vertebral artery dissection presenting as
      isolated occipital headache and/or neck pain].
AB  - Vertebral artery dissection(VAD)presenting as isolated occipital headache and/or
      neck pain is being increasingly diagnosed because of the development of magnetic
      resonance imaging(MRI). While a majority of the patients diagnosed with this
      condition shows a favorable prognosis, the pain may be a predictor of fatal
      stroke in some patients. We aimed to find out the features of headache with VAD,
      identify the clinical manifestations indicative of VAD, and determine the ideal
      diagnostic approach to this condition to avoid fatal stroke. We reviewed medical
      records of 41 consecutive patients who showed VAD with isolated headache and were
      diagnosed between 1995 and 2008. All patients experienced pain in the
      occipitocervical area ipsilateral to the affected VA. Pain showed a sudden onset
      in 21(51%)patients, was persistent over several days in 31(76%)patients, and was
      severe enough to disable daily life activities in 34(83%)patients. Progression of
      stenosis or aneurysmal dilatation of the vessel was identified on follow-up
      imaging(angiography, magnetic resonance angiography)in 7 patients(17%), and was
      found within 14 days after pain onset in 6 of these patients(86%). Patients with
      persistent, severe, and unilateral pain in the occipitocervical area should
      undergo MRI examination, including surface anatomy scanning(SAS)imaging, and the
      possibility of VAD should be considered in their diagnosis. Once VAD is
      diagnosed, the patient should undergo meticulous blood pressure control, bed
      rest, and repeated MRI examination for at least 2 weeks after onset.

PMID- 23542793
TI  - [The limits and countermeasures of the anterior temporal approach for unruptured
      upper basilar artery aneurysms].
AB  - BACKGROUND AND PURPOSE: In general, upper basilar artery aneurysms are treated
      following the transsylvian or subtemporal approach. These approaches have both
      advantages and disadvantages. Therefore, we followed the anterior temporal
      approach that provides a wider surgical field in the retro-carotid space.
      METHODS: We reviewed the clinical records of 37 patients with an upper basilar
      artery aneurysm operated on following the anterior temporal approach between 2002
      and 2012 in our institute, and evaluated the usefulness of this approach.
      RESULTS: In 23 cases, several additional techniques were performed. In all these
      cases a wide operation field was obtained in the retro-carotid space and the
      aneurysm was completely obliterated. The post operative adverse events were
      temporary oculomotor palsy in 6 cases, permanent oculomotor palsy in 3 and
      temporary epilepsy, aphasia due to venous infarction and asymptomatic cerebral
      infarction in 1 case each. CONCLUSIONS: The anterior temporal approach allows the
      additional use of several techniques and provides a wide surgical field.
      Therefore, we consider this approach is useful to reach and treat upper basilar
      artery aneurysms.

PMID- 23542794
TI  - [Chronic subdural hematoma (CSH) complicated by bilateral occipital lobe
      infarction: two case reports].
AB  - Chronic subdural hematoma (CSH) is a common disease that is treated with burr
      hole drainage by neurosurgeons. The outcome of CSH is mostly favorable. We
      treated 2 cases with bilateral occipital lobe infarction due to CSH. A 57-year
      old woman was ambulatory when she visited a clinic for evaluation of headache.
      One hour after the CT was taken, she developed acute impairment of consciousness,
      so that she was referred to our hospital. The second patient was a 73-year-old
      woman with a history of depression who was involved in a traffic accident 5 weeks
      before admission to our hospital. She was at first admitted to a psychiatric
      hospital for evaluation of gait disturbance. Three weeks after she was admitted
      to the psychiatric hospital, she fell into a coma. She was referred to our
      hospital. Their brain CT on admission revealed compressed ambient and
      interpeduncular cistern and bilateral CSH. Although burr hole drainage surgery
      was performed, the 2 patients developed severe sequelae due to occipital lobe
      infarction caused by central transtentorial herniation.

PMID- 23542795
TI  - [Allergy of calcium phosphate cement material following skull reconstruction: a
      case report].
AB  - The paste form of calcium phosphate cement is often used in skull reconstruction
      because of the biocompatibility and early handling of these cements. Although it
      had rarely been shown to produce a foreign body reaction, we encountered a
      patient who experienced an allergic reaction to calcium phosphate
      cements(Biopex(r). A patch test was performed and a positive reaction to
      magnesium phosphate was obtained. Biopex(r) contains magnesium phosphate, so we
      diagnosed this case as allergic reaction. Pathological analysis revealed
      infiltration of plasmacytes in the bone flap around the calcium phosphate cement.
      The postoperative course was uneventful 3 years after surgery. Allergy to calcium
      phosphate cements is rare, but must be considered in differential diagnosis of
      its side effects.

PMID- 23542796
TI  - [A case of occipital diploic dermoid tumor with perforation of the dura].
AB  - Along with epidermoid cysts, dermoid cysts are uncommon, benign and slow-growing
      lesions. We described a case of diploic dermoid cyst of the occipital bone with
      an intracranial extension in the right posterior fossa diagnosed and subjected to
      pathological examination. A 63-year-old man presented with dizziness at the time
      of posture conversion. Magnetic resonance imaging(MRI)showed a heterogenous hypo
      intensity area on T1-weighted image, hyper-intensity on T2-weighted image and
      remarkably-strong intensity on diffusion-weighted image. Gadolinium enhancement
      was partially seen in the tumor capsule. Bone density computed tomography (CT)
      and 3-dimensional CT using helical CT scan revealed the osteolytic range with
      destruction of the inner and outer table. From these findings, this tumor was
      diagnosed as diploic epidermoid cyst before surgery. The tumor was totally
      removed and underwent cranioplasty with a titanium plate. However, pathological
      examination confirmed dermoid cyst with existence of sebaceous gland in some cyst
      walls. It was difficult to diagnose this case as dermoid tumor from radiological
      features before surgery.

PMID- 23542797
TI  - [Vertebral artery dissecting aneurysm presenting with isolated pain and showing
      repeated morphological changes over the short term: a case report].
AB  - Vertebral artery (VA) dissecting aneurysm (VADA), which presents with headache
      and neck pain as the only manifestations, is an uncommon pathology, but is
      increasingly recognized as a cause of posterior circulation stroke in young
      adults. We report a case of VADA with isolated occipital headache at the time of
      onset and treatment using an endovascular approach. A 58-year-old man was
      admitted to our hospital with left occipital headache. Cranial magnetic resonance
      imaging (MRI) showed neither subarachnoid hemorrhage(SAH)nor cerebral infarction,
      but magnetic resonance angiography (MRA)revealed left VADA. Conservative
      treatment including pain relief and blood pressure control was provided. After 2
      weeks, the dissecting lesion showed spontaneous improvement and occipital
      headache was gradually improving. However, 4 months after onset, the VADA showed
      growing aneurysmal dilatation. We therefore performed endovascular surgery (coil
      embolization with parent artery occlusion). Symptoms improved, and the
      postoperative course was uneventful. Although the natural history of VADA with
      isolated headache remains unclear, endovascular treatment should be considered
      for patients with growing aneurysmal dilatation, since the prognosis for patients
      with subsequent SAH is very poor.

PMID- 23542798
TI  - [Required knowledge for neuroendovascular surgeon (8) endovascular
      revascularization for extra- and intra-cranial vessels except carotid artery
      stenting].

PMID- 23542799
TI  - [Systematic review of complications for proper informed consent (7) surgery for
      convexity/parasagittal/falx meningiomas].

PMID- 23542800
TI  - Protective mechanical ventilation during general anesthesia for open abdominal
      surgery improves postoperative pulmonary function.
AB  - BACKGROUND: The impact of intraoperative ventilation on postoperative pulmonary
      complications is not defined. The authors aimed at determining the effectiveness
      of protective mechanical ventilation during open abdominal surgery on a modified
      Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary
      function. METHODS: Prospective randomized, open-label, clinical trial performed
      in 56 patients scheduled to undergo elective open abdominal surgery lasting more
      than 2 h. Patients were assigned by envelopes to mechanical ventilation with
      tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory
      pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body
      weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers
      (protective ventilation strategy). Modified Clinical Pulmonary Infection Score,
      gas exchange, and pulmonary functional tests were measured preoperatively, as
      well as at days 1, 3, and 5 after surgery. RESULTS: Patients ventilated
      protectively showed better pulmonary functional tests up to day 5, fewer
      alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at
      days 1, 3, and 5 (mmHg; mean +/- SD): 77.1 +/- 13.0 versus 64.9 +/- 11.3 (P =
      0.0006), 80.5 +/- 10.1 versus 69.7 +/- 9.3 (P = 0.0002), and 82.1 +/- 10.7 versus
      78.5 +/- 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection
      Score was lower in the protective ventilation strategy at days 1 and 3. The
      percentage of patients in hospital at day 28 after surgery was not different
      between groups (7 vs. 15% respectively, P = 0.42). CONCLUSION: A protective
      ventilation strategy during abdominal surgery lasting more than 2 h improved
      respiratory function and reduced the modified Clinical Pulmonary Infection Score
      without affecting length of hospital stay.

PMID- 23542801
TI  - Nitrous oxide genotoxicity.

PMID- 23542802
TI  - Coadministration of the AMPAKINE CX717 with propofol reduces respiratory
      depression and fatal apneas.
AB  - BACKGROUND: Propofol (2,6-diisopropylphenol) is used for the induction and
      maintenance of anesthesia in human and veterinary medicine. Propofol's
      disadvantages include the induction of respiratory depression and apnea. Here,
      the authors report a clinically feasible pharmacological solution for reducing
      propofol-induced respiratory depression via a mechanism that does not interfere
      with anesthesia. Specifically, they test the hypothesis that the AMPAKINE CX717,
      which has been proven metabolically stable and safe for human use, can prevent
      and rescue from propofol-induced severe apnea. METHODS: The actions of propofol
      and the AMPAKINE CX717 were measured via (1) ventral root recordings from newborn
      rat brainstem-spinal cord preparations, (2) phrenic nerve recordings from an
      adult mouse in situ working heart-brainstem preparation, and (3) plethysmographic
      recordings from unrestrained newborn and adult rats. RESULTS: In vitro,
      respiratory depression caused by propofol (2 MUM, n = 11, mean +/- SEM, 41 +/- 5%
      of control frequency, 63 +/- 5% of control duration) was alleviated by CX717 (n =
      4, 50-150 MUM). In situ, a decrease in respiratory frequency (44 +/- 9% of
      control), phrenic burst duration (66 +/- 7% of control), and amplitude (78 +/- 5%
      of control) caused by propofol (2 MUM, n = 5) was alleviated by coadministration
      of CX717 (50 MUM, n = 5). In vivo, pre- or coadministration of CX717 (20-25mg/kg)
      with propofol markedly reduced propofol-induced respiratory depression (n = 7;
      20mg/kg) and propofol-induced lethal apnea (n = 6; 30 mg/kg). CONCLUSIONS:
      Administration of CX717 before or in conjunction with propofol provides an
      increased safety margin against profound apnea and death.

PMID- 23542803
TI  - A novel serum metabolomics-based diagnostic approach to pancreatic cancer.
AB  - BACKGROUND: To improve the prognosis of patients with pancreatic cancer, more
      accurate serum diagnostic methods are required. We used serum metabolomics as a
      diagnostic method for pancreatic cancer. METHODS: Sera from patients with
      pancreatic cancer, healthy volunteers, and chronic pancreatitis were collected at
      multiple institutions. The pancreatic cancer and healthy volunteers were randomly
      allocated to the training or the validation set. All of the chronic pancreatitis
      cases were included in the validation set. In each study, the subjects' serum
      metabolites were analyzed by gas chromatography mass spectrometry (GC/MS) and a
      data processing system using an in-house library. The diagnostic model
      constructed via multiple logistic regression analysis in the training set study
      was evaluated on the basis of its sensitivity and specificity, and the results
      were confirmed by the validation set study. RESULTS: In the training set study,
      which included 43 patients with pancreatic cancer and 42 healthy volunteers, the
      model possessed high sensitivity (86.0%) and specificity (88.1%) for pancreatic
      cancer. The use of the model was confirmed in the validation set study, which
      included 42 pancreatic cancer, 41 healthy volunteers, and 23 chronic
      pancreatitis; that is, it displayed high sensitivity (71.4%) and specificity
      (78.1%); and furthermore, it displayed higher sensitivity (77.8%) in resectable
      pancreatic cancer and lower false-positive rate (17.4%) in chronic pancreatitis
      than conventional markers. CONCLUSIONS: Our model possessed higher accuracy than
      conventional tumor markers at detecting the resectable patients with pancreatic
      cancer in cohort including patients with chronic pancreatitis. IMPACT: It is a
      promising method for improving the prognosis of pancreatic cancer via its early
      detection and accurate discrimination from chronic pancreatitis.

PMID- 23542804
TI  - Time to first cigarette and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
      levels in adult smokers; National Health and Nutrition Examination Survey
      (NHANES), 2007-2010.
AB  - BACKGROUND: The time to first cigarette (TTFC) is a good indicator of several
      dimensions of nicotine dependence. An early TTFC is also associated with
      increased lung and oral cancer risk. Our objective was to determine the
      relationship between TTFC and exposure to tobacco smoke carcinogens. METHODS: We
      conducted a cross-sectional analysis of a nationally representative subsample of
      smoking adults that had urinary samples analyzed for tobacco biomarkers. The
      study included 1,945 participants from the 2007-2008 and 2009-2010 National
      Health and Nutrition and Examination Survey. The main outcome measure was
      creatinine-adjusted urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
      levels. RESULTS: The cigarette-per-day adjusted levels of NNAL were twice as high
      in participants who smoked within 5 minutes after waking than in participants who
      refrained from smoking for at least 1 hour (0.58 vs. 0.28 ng/mL, P < 0.001). In
      multivariate linear models, a shorter TTFC was significantly associated with
      increasing NNAL levels, after adjusting for cigarettes smoked per day (or
      cotinine), secondhand smoke exposure, age, sex, race/ethnicity, and other
      potential confounders. CONCLUSIONS: These data show that in a nationally
      representative sample, there is a dose-dependent relationship between earlier
      smoking in the day and higher biologic exposure to a tobacco smoke carcinogen.
      IMPACT: Our study provides further evidence that highlights the relationship
      between TTFC, nicotine dependence, and cancer risk.

PMID- 23542805
TI  - Dairy intakes in older girls and risk of benign breast disease in young women.
AB  - Previous investigations found high dairy intakes in girls associated with rapid
      height growth and excess weight gain, which had opposite relationships with
      benign breast disease (BBD) in young women. We use data from the longitudinal
      Growing Up Today Study (GUTS) to investigate whether dairy intakes, in older
      children/adolescents, are associated with BBD risk in young women. GUTS includes
      9,039 females, ages 9-15 years in 1996, who completed questionnaires annually
      through 2001, then in 2003, 2005, 2007, and 2010. Dietary food frequencies (1996
      2001) obtained milk, yogurt, and cheese intakes. On 2005-2010 surveys, 7,011
      females (18-29 years) reported whether a health care provider ever diagnosed them
      with BBD (n = 250) and if confirmed by breast biopsy (n = 105). Logistic
      regression models estimated associations between prevalent biopsy-confirmed BBD
      and dairy intakes, adjusted for age and energy. Multivariable-adjusted models
      additionally included menarche age, childhood adiposity, adolescent alcohol
      consumption, and pregnancy. Further analyses stratified by family history. Age
      energy-adjusted models of dairy (milk, yogurt, cheese, total dairy servings,
      dairy protein, dairy fat) intakes at 14 yr found no significant associations with
      BBD risk [milk: OR, 0.90/(serving/d); 95% confidence interval (CI), 0.76-1.05;
      dairy protein: OR, 0.98/(10 g/d); 95% CI, 0.82-1.17). Separate analyses of dairy
      intakes at 10 yr, intakes before the growth spurt, during the growth spurt,
      before menses-onset, and after menses-onset provided no significant associations
      with BBD. Multivariable adjustment, and family history stratification, did not
      alter the above findings. We conclude that dairy intakes by older girls have no
      strong relation with BBD risk in young women. Because of small number of cases,
      it is important to continue follow-up and re-examine later.

PMID- 23542806
TI  - Attention network test--the impact of social information on executive control,
      alerting and orienting.
AB  - According to the attention network approach, attention is best understood in
      terms of three functionally and neuroanatomically distinct networks - alerting,
      orienting, and executive attention. An important question is whether social
      information influences the efficiency of these networks. Using the same structure
      as the Attentional Network Test (ANT), we developed a variant of this test to
      examine attentional effects in response to stimuli with and without social
      cognitive content. Fish, drawings or photographs of faces looking to the left or
      right were used as target stimuli. Results collected from twenty-four university
      students showed that photographs of faces positively affected attentional
      orienting and executive control, whereas reduced the efficiency of alerting, as
      compared to both face drawings and fish. These results support the status of
      human faces as a special class of visual stimuli for the human attentional
      systems.

PMID- 23542807
TI  - Interference control in adult ADHD: no evidence for interference control deficits
      if response speed is controlled by delta plots.
AB  - Several theoretical accounts assume that interference control deficits belong to
      the core symptoms of adult ADHD. However, findings of increased interference
      effects in adult ADHD patients compared with healthy adults may be confounded
      with the simultaneous finding of generally slower responses in the patient group.
      The current study compared the magnitude of the interference effect in the Stroop
      task between a group of adults with ADHD and a healthy adult control group in a
      procedure that accounted for differences in overall response speed by using delta
      plots. The amount of interference did not differ between patient and control
      group at comparable reaction time levels. These results challenge the conclusions
      of the previous studies, in that they indicate that interference control is not
      impaired in adult ADHD.

PMID- 23542808
TI  - Gender recognition depends on type of movement and motor skill. Analyzing and
      perceiving biological motion in musical and nonmusical tasks.
AB  - Gender recognition in point-light displays was investigated with regard to body
      morphology cues and motion cues of human motion performed with different levels
      of technical skill. Gestures of male and female orchestral conductors were
      recorded with a motion capture system while they conducted excerpts from a
      Mendelssohn string symphony to musicians. Point-light displays of conductors were
      presented to observers under the following conditions: visual-only, auditory
      only, audiovisual, and two non-conducting conditions (walking and static images).
      Observers distinguished between male and female conductors in gait and static
      images, but not in visual-only and auditory-only conducting conditions. Across
      all conductors, gender recognition for audiovisual stimuli was better than
      chance, yet significantly less reliable than for gait. Separate analyses for two
      groups of conductors indicated an expertise effect in that novice conductors'
      gender was perceived above chance level for visual-only and audiovisual
      conducting, while skilled conducting gestures of experts did not afford gender
      specific cues. In these conditions, participants may have ignored the body
      morphology cues that led to correct judgments for static images. Results point to
      a response bias such that conductors were more often judged to be male. Thus
      judgment accuracy depended both on the conductors' level of expertise as well as
      on the observers' concepts, suggesting that perceivable differences between men
      and women may diminish for highly trained movements of experienced individuals.

PMID- 23542810
TI  - Looking at the world with your ears: how do we get the size of an object from its
      sound?
AB  - Identifying the properties of on-going events by the sound they produce is
      crucial for our interaction with the environment when visual information is not
      available. Here, we investigated the ability of listeners to estimate the size of
      an object (a ball) dropped on a plate with ecological listening conditions (balls
      were dropped in real time) and response methods (listeners estimate ball-size by
      drawing a disk). Previous studies had shown that listeners can veridically
      estimate the size of objects by the sound they produce, but it is yet unclear
      which acoustical index listeners use to produce their estimates. In particular,
      it is unclear whether listeners listen to amplitude (related to loudness) or
      frequency (related to the sound's brightness) domain cue to produce their
      estimates. In the current study, in order to understand which cue is used by the
      listener to recover the size of the object, we manipulated the sound source event
      in such a way that frequency and amplitude cues provided contrasting size
      information (balls were dropped from various heights). Results showed that
      listeners' estimations were accurate regardless of the experimental manipulations
      performed in the experiments. In addition, results suggest that listeners were
      likely integrating frequency and amplitude acoustical cues in order to produce
      their estimate and although these cues were often providing contrasting size
      information.

PMID- 23542809
TI  - Impaired retention is responsible for temporal order memory deficits in mild
      cognitive impairment.
AB  - Temporal order memory, or remembering the order of events, is critical for
      everyday functioning and is difficult for patients with mild cognitive impairment
      (MCI). It is currently unclear whether these patients have difficulty acquiring
      and/or retaining such information and whether deficits in these patients are in
      excess of "normal" age-related declines. Therefore, the current study examined
      age and disease-related changes in temporal order memory as well as whether
      memory load played a role in such changes. Young controls (n=25), older controls
      (n=34), and MCI patients (n=32) completed an experimental task that required the
      reconstruction of sequences that were 3, 4, or 5 items in length both immediately
      after presentation (i.e., immediate recall) and again after a 10-min delay (i.e.,
      delayed recall). During the immediate recall phase, there was an effect of age
      largely due to reduced performance at the two longest span lengths. Older
      controls and MCI patients only differed during the five span (controls>MCI).
      During the delayed recall, however, there were significant effects of both age
      and MCI regardless of span length. In MCI patients, immediate recall was
      significantly correlated with measures of executive functioning, whereas delayed
      recall performance was only related to other memory tests. These findings suggest
      that MCI patients experience initial temporal order memory deficits at the point
      when information begins to exceed working memory capacity and become dependent on
      medial temporal lobe functioning. Longer-term deficits are due to an inability to
      retain information, consistent with the characteristic medial temporal lobe
      dysfunction in MCI.

PMID- 23542811
TI  - Is comprehension of problem solutions resistant to misleading heuristic cues?
AB  - Previous studies in the domain of metacomprehension judgments have primarily used
      expository texts. When these texts include illustrations, even uninformative
      ones, people were found to judge that they understand their content better. The
      present study aimed to delineate the metacognitive processes involved in
      understanding problem solutions - a text type often perceived as allowing
      reliable judgments regarding understanding, and was not previously considered
      from a metacognitive perspective. Undergraduate students faced difficult
      problems. They then studied solution explanations with or without uninformative
      illustrations and provided judgments of comprehension (JCOMPs). Learning was
      assessed by application to near-transfer problems in an open-book test format. As
      expected, JCOMPs were polarized - they tended to reflect good or poor
      understanding. Yet, JCOMPs were higher for the illustrated solutions and even
      high certainty did not ensure resistance to this effect. Moreover, success in the
      transfer problems was lower in the presence of illustrations, demonstrating a
      bias stronger than that found with expository texts. Previous studies have
      suggested that weak learners are especially prone to being misled by superficial
      cues. In the present study, matching the difficulty of the task to the ability of
      the target population revealed that even highly able participants were not immune
      to misleading cues. The study extends previous findings regarding potential
      detrimental effects of illustrations and highlights aspects of the
      metacomprehension process that have not been considered before.

PMID- 23542812
TI  - Emotion regulation and attachment: relationships with children's secure base,
      during different situational and social contexts in naturalistic settings.
AB  - This study investigated the relationships between children's secure base and
      emotion regulation, namely their behavioral strategies and emotional
      expressiveness, during different situational and social contexts in naturalistic
      settings. Fifty-five children ranging in age from 18 to 26 months of age and
      their mothers participated in this study. Children were exposed to three
      situational (fear, positive affect and frustration/anger) and two social
      (maternal constraint and involvement) contexts. Toddlers' behavioral strategies
      differed as function of emotion-eliciting context, maternal involvement and
      attachment quality. Emotional expressiveness varied as function of an interaction
      involving situational contexts, maternal involvement and children's attachment
      security.

PMID- 23542813
TI  - Assessment of gastric emptying in non-obese diabetic mice using a [13C]-octanoic
      acid breath test.
AB  - Gastric emptying studies in mice have been limited by the inability to follow
      gastric emptying changes in the same animal since the most commonly used
      techniques require killing of the animals and postmortem recovery of the
      meal(1,2). This approach prevents longitudinal studies to determine changes in
      gastric emptying with age and progression of disease. The commonly used [(13)C]
      octanoic acid breath test for humans(3) has been modified for use in mice(4-6)
      and rats(7) and we previously showed that this test is reliable and responsive to
      changes in gastric emptying in response to drugs and during diabetic disease
      progression(8). In this video presentation the principle and practical
      implementation of this modified test is explained. As in the previous study, NOD
      LtJ mice are used, a model of type 1 diabetes(9). A proportion of these mice
      develop the symptoms of gastroparesis, a complication of diabetes characterized
      by delayed gastric emptying without mechanical obstruction of the stomach(10).
      This paper demonstrates how to train the mice for testing, how to prepare the
      test meal and obtain 4 hr gastric emptying data and how to analyze the obtained
      data. The carbon isotope analyzer used in the present study is suitable for the
      automatic sampling of the air samples from up to 12 mice at the same time. This
      technique allows the longitudinal follow-up of gastric emptying from larger
      groups of mice with diabetes or other long-standing diseases.

PMID- 23542814
TI  - Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine
      in brain and liver mitochondria.
AB  - Mitochondrial function and energy metabolism are affected in brains of human
      cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac
      and hepatic tissues, but its effects on brain bioenergetics are less documented.
      Furthermore, the combination of cocaine and opioids (speedball) was also shown to
      induce mitochondrial dysfunction. In this work, we compared the effects of
      cocaine and/or morphine on the bioenergetics of isolated brain and liver
      mitochondria, to understand their specific effects in each tissue. Upon
      energization with complex I substrates, cocaine decreased state-3 respiration in
      brain (but not in liver) mitochondria and decreased uncoupled respiration and
      mitochondrial potential in both tissues, through a direct effect on complex I.
      Morphine presented only slight effects on brain and liver mitochondria, and the
      combination cocaine+morphine had similar effects to cocaine alone, except for a
      greater decrease in state-3 respiration. Brain and liver mitochondrial
      respirations were differentially affected, and liver mitochondria were more prone
      to proton leak caused by the drugs or their combination. This was possibly
      related with a different dependence on complex I in mitochondrial populations
      from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial
      complex I dysfunction in isolated brain and liver mitochondria, with specific
      effects in each tissue.

PMID- 23542815
TI  - Arsenic trioxide induces cardiac fibroblast apoptosis in vitro and in vivo by up
      regulating TGF-beta1 expression.
AB  - Arsenic trioxide (As2O3; ATO) is clinically effective in treating acute
      promyelocytic leukemia (APL); however, it frequently causes cardiotoxic effects.
      This study was designed to investigate whether ATO could induce apoptosis of
      cardiac fibroblasts (CFs) that play very important roles in maintaining the
      structure integrity and function of the heart. Cardiac fibroblasts from guinea
      pigs administered with ATO (1mg/kgbw) were used to test the pro-apoptotic role of
      ATO in vivo. The current study demonstrated that ATO induced morphological
      characteristics of apoptosis and Caspase-3 activation in CFs of guinea pigs along
      with a significant up-regulation in TGF-beta1 protein expression, Bax/Bcl-2 ratio
      and ERK1/2 phosphorylation. In vitro MTT assay showed that ATO remarkably reduced
      the viability of cultured cardiac fibroblasts (NRCFs) from neonatal rat in a
      concentration- and time-dependent manner. Consistent with the notions in vivo,
      ATO significantly induced the apoptosis in NRCFs, dramatically up-regulated TGF
      beta1 protein level and Bax/Bcl-2 ratio in a time-dependent fashion and activated
      Caspase-3 and ERK1/2. Finally, pretreatment with LY364947, an inhibitor of TGF
      beta signaling could apparently reverse these changes. We therefore conclude that
      TGF-beta is functionally linked to ERK1/2 and that TGF-beta signaling is
      responsible for ATO-induced CFs apoptosis, which provides a novel mechanism of
      ATO related cardiac toxicology.

PMID- 23542816
TI  - In utero phthalate effects in the female rat: a model for MRKH syndrome.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and
      vaginal canal aplasia in normal karyotype human females and is a syndrome with
      poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs
      in rat offspring exposed in utero, a phenomenon that is better studied in male
      offspring than females. The current study reports female reproductive tract
      malformations in the Sprague-Dawley rat similar to those characteristic of MRKH
      syndrome, following in utero exposure to a mixture of 5 PEs. We determined that
      females are ~2-fold less sensitive to the effects of the 5-PE mixture than males
      for reproductive tract malformations. We were not fully successful in defining
      the critical exposure period for females; however, incidence of malformations was
      88% following dosing from GD8 to 19 versus 22% and 0% for GD8-13 and GD14-19,
      respectively. Overall, this study provides valuable information regarding female
      vulnerability to in utero phthalate exposure and further characterizes a
      potential model for the human MRKH syndrome. 

PMID- 23542818
TI  - Endocrine effects of chemicals: aspects of hazard identification and human health
      risk assessment.
AB  - Hazard and risk assessment of chemicals with endocrine activity is hotly debated
      due to claimed non-monotonous dose-response curves in the low-dose region. In
      hazard identification a clear definition of "endocrine disruptors" (EDs) is
      required; this should be based on the WHO/IPCS definition of EDs and on adverse
      effects demonstrated in intact animals or humans. Therefore, endocrine effects
      are a mode of action potentially resulting in adverse effects; any classification
      should not be based on a mode of action, but on adverse effects. In addition,
      when relying on adverse effects, most effects reported in the low-dose region
      will not qualify for hazard identification since most have little relation to an
      adverse effect. Non-monotonous dose-response curves that had been postulated from
      limited, exploratory studies could also not be reproduced in targeted studies
      with elaborate quality assurance. Therefore, regulatory agencies or advisory
      bodies continue to apply the safety-factor method or the concept of "margin-of
      exposure" based on no observed adverse effect levels (NOAELs) in the risk
      assessment of chemicals with weak hormonal activity. Consistent with this
      approach, tolerable levels regarding human exposure have been defined for such
      chemicals. To conclusively support non-monotonous dose-response curves, targeted
      experiments with a sufficient number of animals, determination of adverse
      endpoints, adequate statistics and quality control would be required. 

PMID- 23542817
TI  - Disruption of the integrity and function of brain microvascular endothelial cells
      in culture by exposure to diesel engine exhaust particles.
AB  - Diesel exhaust particles (DEPs), a by-product of diesel engine exhaust (DEE), are
      known to produce pro-oxidative and pro-inflammatory effects, thereby leading to
      oxidative stress-induced damage. Given the key role of DEPs in inducing oxidative
      stress, we investigated the role of DEPs in disrupting the integrity and function
      of immortalized human brain microvascular endothelial cells (HBMVEC). To study
      this, HBMVEC cells were exposed to media containing three different
      concentrations of DEPs or plain media for 24h. Those exposed to DEPs showed
      significantly higher oxidative stress than the untreated group, as indicated by
      the glutathione (GSH) and malondialdehyde (MDA) levels, and the glutathione
      peroxidase and glutathione reductase activities. DEPs also induced oxidative
      stress-related disruption of the HBMVEC cells monolayer, as measured by trans
      epithelial electrical resistance. Taken together, these data suggest that DEPs
      induce cell death and disrupt the function and integrity of HBMVEC cells,
      indicating a potential role of DEPs in neurotoxicities.

PMID- 23542819
TI  - The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2
      potassium channel.
AB  - Mancozeb (manganese/zinc ethylene bis-dithiocarbamate) is an organometallic
      fungicide that has been associated with human neurotoxicity and
      neurodegeneration. In a high-throughput screen for modulators of KCNQ2 channel, a
      fundamental player modulating neuronal excitability, Mancozeb, was found to
      significantly potentiate KCNQ2 activity. Mancozeb was validated
      electrophysiologically as a KCNQ2 activator with an EC50 value of 0.92+/-0.23MUM.
      Further examination showed that manganese but not zinc ethylene bis
      dithiocarbamate is the active component for the positive modulation effects. In
      addition, the compounds are effective when the metal ions are substituted by iron
      but lack potentiation activity when the metal ions are substituted by sodium,
      signifying the importance of the metal ion. However, the iron (Fe(3+)) alone,
      organic ligands alone or the mixture of iron with the organic ligand did not show
      any potentiation effect, suggesting as the active ingredient is a specific
      complex rather than two separate additive or synergistic components. Our study
      suggests that potentiation on KCNQ2 potassium channels might be the possible
      mechanism of Mancozeb toxicity in the nervous system.

PMID- 23542820
TI  - Mesenchymal stem cells and neuroregeneration in Parkinson's disease.
AB  - Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized
      by a progressive and extensive loss of dopaminergic (DA) neurons in the
      substantia nigra pars compacta (SNpc) and their terminals in the striatum, which
      results in debilitating movement disorders. This devastating disease affects over
      1 million individuals in the United States and is increasing in incidence
      worldwide. Currently available pharmacological and surgical therapies ameliorate
      clinical symptoms in the early stages of disease, but they cannot stop or reverse
      degeneration of DA neurons. Stem cell therapies have come to the forefront of the
      PD research field as promising regenerative therapies. The majority of
      preclinical stem cell studies in experimental models of PD are focused on the
      idea that stem cell-derived DA neurons could be developed for replacement of
      diseased neurons. Alternatively, our studies and the studies from other groups
      suggest that stem cells also have the potential to protect and stimulate
      regeneration of compromised DA neurons. This review is focused on strategies
      based on the therapeutic potential for PD of the neurotrophic and
      neuroregenerative properties of a subclass of stem cells, mesenchymal stem cells
      (MSCs).

PMID- 23542821
TI  - Prevalence of Sexually Transmitted Infections (HIV, Hepatitis B, Herpes Simplex
      Type 2 and Syphilis) Among Asymptomatic Pregnant Women.
AB  - OBJECTIVES: To determine the current prevalence of four major sexually
      transmitted infections (STIs: HIV, Hepatitis B, Herpes simplex virus 2, and
      Syphilis) in asymptomatic pregnant women. METHODS: This is a prospective study of
      500 consecutive, apparently healthy asymptomatic pregnant women who were
      attending the antenatal clinic. The information regarding their socio-demographic
      and behavioral characteristics and obstetric performance was recorded. The blood
      samples was collected after obtaining their informed written consent from those
      who were tested for the HIV antibodies (NACO guidelines), HBsAg (ELISA test),
      HSV2-IgM (ELISA test), and Syphilis (VDRL and TPHA tests). RESULTS: The overall
      prevalence of one or the other four STIs studied was 4.8 % with the highest
      prevalence of HBV (2.4 %), followed by HSV-2 (2 %), and HIV (0.4 %). No woman
      tested positive for syphilis and multiple infections. All the infections were
      more common in illiterate, multigravida, monogamous women of low socio-economic
      status. High-risk sexual behavior of the husbands, history of STIs in husbands,
      and blood transfusions were the other factors associated with the prevalence of
      these infections. CONCLUSIONS: The relatively high prevalence of HBV and HSV-2
      infections in asymptomatic pregnant women suggests that there is need of
      screening for HBV and HSV-2 infections along with the pre-existing screening for
      HIV and Syphilis and universal immunization of HBV high-risk infants.

PMID- 23542822
TI  - Clinical characteristics of glaucomatous subjects treated with refractive corneal
      ablation surgery.
AB  - PURPOSE: To evaluate the clinical characteristics of newly diagnosed glaucomatous
      subjects who had a history of refractive corneal ablation surgery (RCAS).
      METHODS: Sixty-eight glaucomatous subjects who had a history of RCAS and 68 age-
      and visual field (VF) mean deviation-matched glaucomatous subjects with no
      history of RCAS were included. Intraocular pressure (IOP), central corneal
      thickness (CCT), VF, and retinal nerve fiber layer thickness determined by
      optical coherence tomography were assessed. Parameters were compared between
      patients with and without a history of RCAS. Between-eye comparisons in the same
      participant (more advanced vs. less-advanced eye, in terms of glaucoma severity)
      were performed in the RCAS group. RESULTS: With similar levels of glaucoma
      severity, those with a history of RCAS showed significantly lower baseline IOP
      and a thinner CCT than the eyes of individuals without a RCAS history (13.6 vs.
      18.7 mmHg, 490.5 vs. 551.7 um, all p < 0.001). However, the extent of IOP
      reduction after anti-glaucoma medication did not significantly differ between the
      two groups (17% vs. 24.3%, p = 0.144). In the between-eye comparisons of
      individual participants in the RCAS group, the more advanced eyes were more
      myopic than the less-advanced eyes (-1.84 vs. -0.58 diopter, p = 0.003).
      CONCLUSIONS: Eyes with a history of RCAS showed a similar level of IOP reduction
      as eyes without such a history after anti-glaucoma medication. Our finding that
      the more advanced eyes were more myopic than the less-advanced eyes in the same
      participant may suggest an association between glaucoma severity and myopic
      regression.

PMID- 23542823
TI  - Safety, tolerability, and clinical response after fecal transplantation in
      children and young adults with ulcerative colitis.
AB  - BACKGROUND AND OBJECTIVE: Colonic dysbiosis contributes to the development of
      colonic inflammation in ulcerative colitis (UC). Fecal microbial transplantation
      (FMT) is being proposed as a novel treatment for UC because it can eliminate
      dysbiosis; however, no prospective data exist. We initiated a pilot study to
      evaluate feasibility and safety of FMT in children with UC. METHODS: Ten
      children, 7 to 21 years of age, with mild-to-moderate UC (pediatric UC activity
      index [PUCAI] between 15 and 65) received freshly prepared fecal enemas daily for
      5 days. Data on tolerability, adverse events, and disease activity were collected
      during FMT and weekly for 4 weeks after FMT. Clinical response was defined as
      decrease in PUCAI by >15, and decrease in PUCAI to <10 was considered clinical
      remission. RESULTS: No serious adverse events were noted. Mild (cramping,
      fullness, flatulence, bloating, diarrhea, and blood in stool) to moderate (fever)
      adverse events were self-limiting. One subject could not retain fecal enemas.
      Average tolerated enema volume by remaining 9 subjects was 165 mL/day. After FMT,
      7 of the 9 (78%) subjects showed clinical response within 1 week, 6 of the 9
      (67%) subjects maintained clinical response at 1 month, and 3 of the 9 (33%)
      subjects achieved clinical remission at 1 week after FMT. Median PUCAI
      significantly improved after FMT (P = 0.03) compared with the baseline.
      CONCLUSIONS: Fecal enemas were feasible and tolerated by children with UC.
      Adverse events were acceptable, self-limiting, and manageable by subjects. FMT
      indicated efficacy in the treatment of UC.

PMID- 23542825
TI  - Neuroanatomy of Cornudescoides kulkarnii n. sp., a gill parasite of Mystus
      vittatus in Meerut (UP), India.
AB  - Chemical named 5-bromo indoxyl acetate has been used to describe the nervous
      system of a viviparous monogenean Cornudescoides Kulkarni (1969), a gill parasite
      of Mystus vittatus. Central nervous system consists of paired cerebral ganglia
      from which anterior and posterior neuronal pathways arise. These neuronal
      pathways are interlinked by cross connectives and commissures. Paired dorsal,
      ventral and lateral nerve cords emanate from the cerebral ganglia, connected at
      intervals by transverse connectives. Huge arrangement of dorsal, ventral and
      lateral nerve cords and their innervations have been examined. Peripheral nervous
      system (PNS) includes innervations of the alimentary tract, reproductive organs
      and attachment organs (anterior adhesive areas and haptor). Both the CNS and PNS
      are bilaterally symmetrical, and better developed ventrally than laterally and
      dorsally.

PMID- 23542824
TI  - Delayed presentation of the traumatic abdominal wall hernia; dilemma in the
      management - review of literature.
AB  - Traumatic abdominal wall hernia is a rare entity, and an uncommon type of
      abdominal wall hernia as far as the etiology is concerned. It is caused by blunt
      trauma and disrupts the fascial layers, but does not disrupt the elastic skin. In
      this study, we report the case of a 60-year-old female, diagnosed with traumatic
      abdominal wall hernia with delayed presentation. In this case, herniation of the
      bowels was present through the defect in the left iliac region. She was
      surgically well-managed. During the follow-up of 1 year, there was no recurrence.
      In the Western medical literature, only a few cases have been reported,
      especially with intra-abdominal injuries. Confusion still exists in the
      management of such a disease as to whether to treat the condition at an early or
      later stage.

PMID- 23542826
TI  - High level expression, purification and characterization of recombinant CCR5 as a
      vaccine candidate against HIV.
AB  - Cysteine-cysteine chemokine receptor type 5 (CCR5) is an important co-receptor
      for human immunodeficiency virus (HIV) infection and CCR5 neutralizing agents
      have proven efficient in patients suffering from HIV infection. Here, we
      expressed and purified various CCR5 vaccines named rCCR5, PADRE-rCCR5, GST-C1 and
      GST-C2 composed of different epitopes of CCR5. Results showed that vaccines
      containing multiple epitopes (rCCR5 and PADRE-rCCR5) induced stronger immune
      responses than single-epitope ones (GST-C1 and GST-C2). In addition, the elicited
      antibodies can specifically bind CCR5(+) U937 but not CCR5(-) Wish cells. These
      results demonstrate that the CCR5 vaccines are useful for further research,
      especially for the in vitro preclinical evaluation of their potential as
      biological CCR5 neutralizing agents.

PMID- 23542827
TI  - Demographic characteristics and needs of families at an urban, low-income,
      multicultural paediatric clinic.
AB  - OBJECTIVES: To describe the demographic characteristics and identify the needs of
      a population attending an urban, low-income area, multicultural paediatric
      clinic. METHODS: Surveys were distributed to caregivers of children zero to 16
      years of age (n=299). RESULTS: Of the children attending appointments, 55% were
      female and 51% were five years of age or younger. Of the caregivers, 29.5% were
      born outside of Canada and 25% reported that their primary spoken language was
      not English. Sixty-six per cent of families had been living in Edmonton for more
      than three years, with two-thirds of respondents living in Edmonton's second
      lowest average household income region. Seventy-six per cent of respondents lived
      in households with four or more persons. CONCLUSIONS: Challenges facing
      individuals attending an urban, low-income area, paediatric clinic include
      language barriers, lower household income and larger family size. Immigrants
      living outside of major Canadian cities are under-represented and may have
      different needs compared with their counterparts in 'gateway' cities. More
      studies are needed to determine their needs, and will ultimately lead to the
      provision of culturally competent care.

PMID- 23542828
TI  - An assessment of the risks and benefits of immediate autologous breast
      reconstruction in patients undergoing postmastectomy radiation therapy.
AB  - BACKGROUND: The utility of immediate autologous breast reconstruction in patients
      likely to undergo radiation therapy remains controversial. The purpose of this
      study was to perform a quantitative outcomes assessment of patients undergoing
      immediate free-flap breast reconstruction and postmastectomy radiation therapy
      (PMRT). METHODS: A retrospective chart review was performed of patients
      undergoing free-flap breast reconstruction by the senior authors (L.C.W. and
      J.M.S.) between 2005 and 2009. The treatment group included patients who
      underwent immediate free-flap breast reconstruction and received PMRT. The
      control group consisted of patients undergoing immediate breast reconstruction
      without PMRT. Variables assessed included postoperative complications and
      revision surgery. RESULTS: Four hundred seven women underwent immediate free-flap
      breast reconstruction for a total of 655 flaps. In the cohort that underwent
      unilateral reconstruction, there was a higher incidence of volume loss (28.26% vs
      4.42%, P < 0.0001) and fat necrosis (19.57% vs 3.54%, P = 0.002) in the PMRT
      group. In the cohort that underwent bilateral reconstruction, there was a higher
      rate of volume loss for those in the PMRT group (19.75% vs 1.0%, P < 0.0001).
      However, for both patients who underwent unilateral reconstruction and those who
      underwent bilateral reconstruction, the PMRT group underwent similar rates of
      revision surgery. The cohort that underwent bilateral reconstruction experienced
      a higher incidence of volume loss in radiated perforator flaps (39%) vs muscle
      sparing free transverse rectus abdominis myocutaneous flaps (12%; P = 0.013).
      CONCLUSIONS: Postmastectomy radiation therapy can result in volume loss and fat
      necrosis, yet there are no increases in other complications or revision
      procedures. The deleterious effects of PMRT do not preclude the decision for
      immediate autologous reconstruction.

PMID- 23542829
TI  - Lymphatic microsurgery to treat lymphedema: techniques and indications for better
      results.
AB  - This study aimed to report new clinical approaches to the treatment of lymphatic
      disorders by microsurgical techniques based on histological and
      immunohistochemical findings. The authors' wide clinical experience in the
      treatment of patients with peripheral lymphedema by microsurgical techniques is
      reported. Microsurgical methods included derivative lymphatic-venous anastomoses
      and lymphatic reconstruction by interpositioned vein grafted shunts. In all
      patients, lymphatic and lymph nodal tissues were sent for histological
      assessment, together with specimen of the interstitial matrix. Diagnostic
      investigations consisted in venous duplex scan and lymphoscintigraphy. Results
      were assessed clinically by volumetry performed preoperatively and
      postoperatively at 3 to 6 months and at 1, 3, and 5 years. The outcome obtained
      in treating lymphedemas at different stages was analyzed for volume reduction,
      stability of results with time, reduction of dermatolymphangioadenitis attacks,
      necessity of wearing elastic supports, and use of conservative measures
      postoperatively. Microsurgical lymphatic derivative and reconstructive techniques
      allow bringing about positive results in the treatment of peripheral lymphedema,
      above all in early stages when tissular changes are slight and allow almost a
      complete restore of lymphatic drainage. 

PMID- 23542830
TI  - Full body photography in the massive weight loss population: an inquiry to
      optimize patient-centered care.
AB  - Medical photography of body contouring patients often requires complete nudity,
      placing patients in a vulnerable situation. We investigated patient perspectives
      on full body photography in an effort to better protect the patients and enhance
      comfort with the photography process. Sixty-five massive weight loss patients
      were identified who underwent body contouring surgery with full body photography.
      Photographs were taken at the time of initial consult, time of marking, and
      postoperatively. A retrospective chart review was performed to assess body mass
      indices and comorbidities, and a telephone survey inquired about several aspects
      of the photographic process. Fifty-six (86%) patients participated. Patients were
      more comfortable at the time of markings (P = 0.0004) and at the postoperative
      session (P = 0.0009). Patients' perception of positive body image increased after
      body contouring surgery (P < 0.0001). Patients who reported being comfortable at
      their initial session had a higher body mass index (P = 0.0027). Professionalism
      of the staff was rated as the most important aspect of the photographic process.
      Patients preferring a chaperone of the same sex tended to be less comfortable
      with the process (P = 0.015). Most patients preferred the surgeon as the
      photographer (P = 0.03). Patient comfort with full body photography improves
      quickly as they move through the surgical process. Maintaining professionalism is
      the most important factor in achieving patient trust and comfort. Limiting the
      number of observers in the room, providing explicit details of the photography
      process, and having at least 1 person of the same sex in the room can optimize
      patient safety and comfort. 

PMID- 23542831
TI  - Caudal resection of the upper lateral cartilages and its measured effect on tip
      rotation.
AB  - BACKGROUND: Commonly used maneuvers for upward tip rotation include cephalic trim
      of the lateral alar cartilages, caudal resection of the septum, and shortening of
      the upper lateral cartilages (ULCs). Few techniques for surgical manipulation of
      the ULCs are found in the literature, and none accurately describe the measured
      effect of the caudal resection on tip rotation. The purpose of this study is to
      predict the change in upward rotation of the nasal tip for a measured incremental
      resection of the ULCs. METHODS: Ten fresh cadaveric noses were dissected with the
      aid of loupe magnification via an open rhinoplasty approach. The ULCs were
      sectioned in 20% increments, and measurements of the nasolabial angle (NLA) were
      recorded with the use of a goniometer. True lateral photographs were obtained for
      the photographic analysis of the specimens. RESULTS: The average length of the
      ULC was 16.8 +/- 1.6 mm. Serial reduction of the ULC length by 4 sequential 20%
      increments resulted in a mean NLA change of 3.6, 2.7, 2.1, and 1.9 degrees,
      respectively. The average incremental change in NLA for the 4 resections was 2.6
      degrees. CONCLUSIONS: Caudal resection of the ULC has a measurable effect on the
      upward rotation of the nasal tip. A 20% resection correlates with an average
      change in the NLA of 2.6 degrees. Because caudal resection of the ULC is a
      powerful tool in the armamentarium of the rhinoplasty surgeon that can cause
      narrowing of the internal nasal valve and hallowing of the lower nasal sidewalls,
      it should be used with caution in a selected group of patients when attempting to
      elevate the "droopy" tip.

PMID- 23542832
TI  - Local anesthesia for lymphaticovenular anastomosis.
AB  - Lymphaticovenular anastomosis is well documented for its effectiveness in
      treating lower limb lymphedema. However, local anesthesia (LA) is not the usual
      choice of anesthesia. In this study, 14 patients having such operation done under
      LA were recruited to see how well they tolerated the operations. Visual analogue
      scale was used to grade both intraoperative and postoperative pain. It was shown
      that the mean intraoperative pain score was never greater than 1, in the scale
      from 0 to 10. The mean postoperative pain score was 1.6 on the first
      postoperative day and then dropped gradually. No complication of surgery was
      reported. In-depth preoperative counseling and complementary intraoperative
      measures were emphasized to make LA a possible choice of anesthesia. 

PMID- 23542833
TI  - Restoration of glans penis defect by a bipedicled foreskin flap.
AB  - Plastic surgeons reconstruct hard and soft tissues in many parts of the human
      body. Penile reconstruction is unique in that the target tissue has to be soft
      but intermittently rigid. There are many ways to treat penile defects. The ideal
      reconstruction must take into considerations sensation, cosmesis, and erectile
      functions. There is limited literature available on the management of penile
      glans defect. In this report, we present the reconstruction of penile glans
      defect, after surgical excision of Bowen disease, using a bipedicled foreskin
      flap of bucket handle type. It is easy to perform and highly effective, and
      importantly, both cosmetic and functional outcomes at 1-year follow-up were quite
      satisfactory. 

PMID- 23542834
TI  - Breast reconstruction with abdominal-based free flaps in high body mass index
      population: postoperative complications and impact of weight loss.
AB  - Obesity, which is becoming endemic in the United States, causes a significant
      challenge for reconstructive surgeons. This study evaluates postoperative
      complications and impact of weight loss in the high body mass index (BMI)
      population undergoing breast reconstruction with abdominal free flaps. A
      retrospective review of 182 consecutive patients was performed. Patients were
      divided into groups according to their BMI at the time of surgery (preoperative
      BMI) and presence of weight loss, and data were compared among groups.
      Multivariate analysis of effect of preoperative BMI on complications revealed
      that overall flap (P = 0.008) and donor (P = 0.016) complication rates were
      significantly higher in the obese group. Analysis of preoperative weight loss did
      not yield a statistically significant reduction in flap (P = 0.5161) or donor (P
      = 0.8034) complication rates. Univariate analysis showed that higher preoperative
      BMI is associated with higher risk of systemic complications (P = 0.027). It is
      important to inform patients preoperatively that weight loss, although beneficial
      for ease of procedure and quality of life, does not diminish their increased risk
      of complications. Body mass index during surgery is the most important predictor
      of complications. 

PMID- 23542835
TI  - Surgical refinements and sensory recovery of using transverse sensate
      thoracodorsal artery perforator flaps to resurface ring-avulsed fingers.
AB  - To improve the use of thoracodorsal artery perforator flaps in resurfacing ring
      avulsed fingers, the relations between the thoracodorsal artery perforators and
      intercostal nerves were investigated. The surgical refinements, clinical results,
      and sensory recovery of flaps were presented. Eleven patients with ring-avulsed
      fingers were reviewed. Separated and conjoint relations were found. Eleven flaps
      were harvested with 3 refinements. First is the transverse flap design. Second is
      operating color Doppler sonography to identify the relations. Third is using the
      conjoint relation to facilitate adequate flap thinning. Four patients had
      separated relation, and 7 patients had conjoint relation. Only 1 patient showed
      flap tip necrosis. Two patients with separated relation needed flap debulking.
      Ten patients acquired protective to normal tactile sensation, and 9 patients
      gained fair to normal discriminative sensation. The free transverse sensate
      thoracodorsal artery perforator flaps can be an option in the reconstruction of
      ring-avulsed fingers. 

PMID- 23542836
TI  - Use of lateral intercostal artery perforator free flaps for resurfacing lower
      extremities.
AB  - Although latissimus dorsi perforator flaps vary less than flaps from other
      regions, we have encountered several cases where reliable perforator arteries
      were absent and we harvested lateral intercostal artery perforator (LICAP) flaps
      instead.Since April 2002, we have attempted to use 97 latissimus dorsi perforator
      flaps to reconstruct lower extremity defects. In 4 cases, no adequate latissimus
      dorsi perforators were present, and in 3 cases, the perforators were too small.
      In all these 7 cases, LICAP were found to be more reliable. The mean pedicle
      length was 5.4 cm, and the average perforator diameter was 0.8 mm. There were no
      surgical complications.In this article, we describe these 7 examples of foot and
      ankle resurfacing using LICAP flaps. Lateral intercostal artery perforator flaps
      may be an alternative in reconstructive surgery of the foot and ankle region when
      reliable perforators cannot be found in the lateral thoracic region. 

PMID- 23542837
TI  - The effects of breast size in unilateral postmastectomy breast reconstruction.
AB  - BACKGROUND: Postmastectomy breast reconstruction is offered to women with breast
      cancer regardless of body habitus and breast size. The decision regarding
      technique for breast reconstruction includes patient preference, risk factors,
      and physical characteristics. The purpose of this study was to determine whether
      there is a relationship between preoperative breast size and choice of
      reconstruction, choice of contralateral breast symmetry procedure, and incidence
      of complications. METHODS: A retrospective review of 355 patients who underwent
      unilateral breast reconstruction at Emory University from 2005 to 2009 was
      performed. Patients were stratified into 3 groups based on mastectomy specimen
      weight with small breasts defined as less than 500 g, medium breasts as 500 to
      1000 g, and large breasts as more than 1000 g. Patient demographics were queried
      including age and risk factors. Additional data points included type of
      reconstruction, contralateral procedure, and complications. RESULTS: There were
      144 patients with small breasts (40.5%), 150 with medium breasts (42.1%), and 62
      with large breasts (17.4%). Women with small breasts were equally likely to
      undergo tissue expander (34%), latissimus dorsi flap (32%), or TRAM/DIEP flap
      (34%) reconstruction. Women with medium breasts were most likely to undergo
      TRAM/DIEP reconstruction (47%), whereas women with large breasts were most likely
      to undergo latissimus dorsi reconstruction (37%; P = 0.134). Small-breasted women
      were more likely to undergo contralateral augmentation (P < 0.0001), which varied
      based on the type of reconstruction. Women with medium-sized breasts were more
      likely to undergo mastopexy (P = 0.033), and large-breasted women were more
      likely to undergo reduction (P < 0.0001). Women with complications had a greater
      mean mastectomy weight than women without complications (744 g compared with 620
      g, P = 0.0062), and there was an increasing incidence of postoperative wound
      infections with increasing breast size (18% of large breasts, 7% of medium
      breasts, and 3% of small breasts; P = 0.0003). CONCLUSIONS: Preoperative breast
      size does play a role when choosing the most appropriate reconstructive option
      and symmetry procedure. Being able to adjust the contralateral breast, however,
      brings the extremes of breast size toward the middle, making most options
      available regardless of initial size and shape. There are noticeable trends in
      technique and outcome when stratified by breast size.

PMID- 23542838
TI  - SPY-Q analysis toolkit values potentially predict mastectomy flap necrosis.
AB  - BACKGROUND: Previously, we and other investigators have reported the benefits of
      using SPY Intraoperative Perfusion Assessment System to assist in the prediction
      of mastectomy flap necrosis. To date, analysis of the SPY images has been
      subjective. However, the new SPY-Q postprocessing software allows for objective
      quantification of SPY images through the application of absolute and relative
      values of fluorescence intensity. This study seeks to determine the use of these
      objective, numerical data and their role in potentially predicting mastectomy
      flap necrosis. METHODS: In a retrospective fashion, 20 SPY images from immediate
      breast reconstructions were randomly selected from a database of more than 100
      images: 10 from breasts that developed flap necrosis and 10 from breasts that
      demonstrated adequate healing. Groups were matched for age, body mass index, and
      comorbidities. The points of necrosis and points of adequate healing were
      evaluated using the postprocessing software, and the groups were compared.
      RESULTS: The mean "relative" fluorescence of the necrosis and the adequate
      healing groups was 25.2% and 43.3%, respectively (P < 0.001). The mean absolute
      fluorescence of the 2 groups was 18.5 and 25.0, respectively (P = 0.07).
      CONCLUSIONS: These findings suggest that quantitative "relative" perfusion values
      as generated by the postprocessing software may augment clinical judgment of flap
      viability in an objective and reproducible fashion.

PMID- 23542839
TI  - The evils of nicotine: an evidence-based guide to smoking and plastic surgery.
AB  - As nearly 1 of 5 adult Americans are smokers, plastic surgeons should be familiar
      with the effect of smoking on perioperative risk, the importance of smoking
      cessation, and the tools to help patients quit. Cigarette smoke contains over 250
      known toxins, including nicotine, carbon monoxide, hydrogen cyanide, and nitric
      oxide, which all are known to impair wound healing, through multiple mechanisms.
      The relationship of smoking and delayed postoperative wound healing has been
      established in numerous prospective and retrospective cohort studies (level 2 and
      3 evidence), and has been demonstrated across a wide range of surgical
      disciplines and procedures, including many common plastic surgical procedures.
      The ameliorating effects of cessation are supported by level 1 evidence, which
      suggests that the optimal duration of preoperative cessation is 4 weeks or
      longer. Nicotine replacement therapy and smoking cessation medications are
      effective aids for quitting and should be familiar to plastic surgeons.

PMID- 23542841
TI  - The evidence base for the acellular dermal matrix AlloDerm: a systematic review.
AB  - BACKGROUND: Many decellularized dermal matrices are available with various
      applications, all with slight differences. AlloDerm appears to have the greatest
      presence in the literature. The purpose of this systematic review is to provide
      an overview of the experience with AlloDerm, stratified by clinical indication.
      METHODS: A literature search was performed across Medline, EMBASE, and the
      Cochrane Collaboration using the search terms "AlloDerm" and "acellular dermal
      matrix." Two independent authors applied a priori inclusion and exclusion
      criteria. Relevant articles were categorized by application, type of study, and
      evidence level. RESULTS: A total of 753 articles met the initial inclusion
      criteria, and 311 remained after discarding irrelevant articles: skin (25), head
      and neck (82), breast (34), trunk (66), pelvis (10), extremities (8), and basic
      science (86). Non-basic science study designs included 32 analytic articles (3
      randomized controlled trials and 29 observational studies including 11 cohort
      studies, 1 cross-sectional study, and 17 case-controlled studies), 192
      descriptive articles (106 case series, 51 case reports, 2 cross-sectional
      studies, and 33 qualitative studies), and 1 systematic review. More than 85% of
      articles had a level of evidence of 4 or 5. Articles showed outcomes that were
      70% positive, 23% neutral, and 7% negative. CONCLUSIONS: AlloDerm has many
      clinical uses with promising results. Most evidence lies in descriptive and
      nonrandomized studies, but randomized trials are emerging. Cost and logistics of
      large trials with these products make large-scale trials challenging but
      necessary. Emphasis needs to shift to randomized controlled trials focusing on
      areas where most clinical benefit can be realized.

PMID- 23542840
TI  - Complications of latissimus dorsi flap breast reconstruction in overweight and
      obese patients.
AB  - The latissimus dorsi flap (LDF) remains a widely used technique for
      postmastectomy autologous tissue breast reconstruction. The purpose of this study
      was to evaluate the effect of body mass index (BMI) on flap and donor-site
      complications in patients undergoing LDF reconstruction. METHODS: All patients at
      Emory University Hospital between 2005 and 2010 who underwent an LDF for breast
      reconstruction were included. Demographics were queried, and patients were
      stratified into 3 groups according to BMI: normal weight (NL; BMI, <25 kg/m),
      overweight (OW; BMI, 25-29.9 kg/m), and obese (OB; BMI, >=30 kg/m). Flap and
      donor-site complications were compared among the groups. RESULTS: There were 277
      patients included in the review: NL (n = 102), OW (n = 72), and OB (n = 103).
      Overall postoperative complication rates for flaps and donor sites were 33.5% and
      22.3%, respectively. The incidence of donor-site complications was similar among
      BMI groups (22.5% vs 19.4% vs 24.2% for NL, OW, and OB groups, respectively).
      Flap-related complications occurred in 28.4% (NL), 33.3% (OW), and 38.8% (OB).
      When stratified by type of complication, no statistically significant difference
      was found in the incidence of seromas and tissue necrosis at the LDF site. Obese
      patients were more likely to develop mastectomy skin flaps necrosis (21.3%)
      compared to the NL group (9.8%, P = 0.042) and less likely to have capsular
      contracture and hematomas (P = 0.009 and 0.023, respectively). No difference was
      observed in the incidence of seroma, hematomas, infection, and skin necrosis of
      the donor site among BMI groups. Patients reconstructed with an LDF and tissue
      expander tended to have more flap-related complications compared to LDF alone
      (36.1% vs 25.3%, P = 0.11). CONCLUSIONS: The incidence of both flap and donor
      site complications after LDF was not significantly different in overweight and
      obese patients compared to the normal weight population. The use of LDFs in
      overweight and obese patients results in an acceptable incidence of postoperative
      complications and can be safely used in this category of patients.

PMID- 23542842
TI  - Lower extremity nerve decompression in burn patients.
AB  - INTRODUCTION: Generalized neuropathy after burn injury is quite common, but the
      diagnosis and management of peripheral nerve compression, late after injury, can
      be difficult. Although the release of upper extremity nerves has been reported,
      the indications, timing, and outcomes of lower extremity nerve decompression,
      after burn injury, are not known. METHODS: We performed a descriptive,
      retrospective, 10-year review of elective peripheral nerve decompression in 107
      burn patients, at a regional burn center. Data collected included age, injury
      type, total body surface area, prior fasciotomy/escharotomy, preoperative
      function, electromyography/nerve conduction studies, time from injury to
      decompression, and decompression site. Main outcome measures included
      postoperative function, complications, and length of follow-up. RESULTS: Sixteen
      patients (mean age, 40.2 years; total body surface area, 31%), with thermal (9),
      electrical (5), and chemical (2) burns, underwent 19 lower extremity nerve
      decompression procedures, a mean of 23 months after injury, at the following
      locations: common peroneal (15), superficial peroneal (2), saphenous (1), and
      sural (1) nerve. Five patients had previous fasciotomy or escharotomy.
      Preoperatively, 6 patients had foot drop (<=2/5 on motor scale), 6 had weak
      dorsiflexion (3-4/5), and 2 had no foot drop but abnormal sensation. There were
      an additional 2 patients who had strictly abnormal sensory findings (1 sural and
      1 saphenous nerve compression), which gave a total of 4 patients with impaired
      sensation. Electromyography/nerve conduction study data were abnormal in 10 of 11
      patients tested. Mean tourniquet time was 35 minutes. Of 19 nerves, 14 (73.6%)
      showed definite improvement, 2 (10.5%) showed mild improvement, and 3 (10.5%)
      showed no improvement in sensorimotor symptoms. Complications included 2 patients
      with dehiscence, 2 patients with cellulitis, and 2 patients with failure to
      improve. Length of follow-up was 20 months. CONCLUSIONS: Lower extremity nerve
      decompression is effective in improving sensory and motor dysfunction, even late
      after burn injury, and should be considered in patients with persistent foot
      drop, paresthesias, and dysesthesias, given the low morbidity of this procedure
      and high potential for improved function.

PMID- 23542843
TI  - Surgical outcomes of gigantomastia breast reduction superomedial pedicle
      technique: a 12-year retrospective study.
AB  - INTRODUCTION: Reduction mammoplasty in patients with gigantomastia can prove a
      challenge for the plastic surgeon. Although several techniques have been
      described to reduce these very large breasts, they can often result in compromise
      of the nipple-areola complex (NAC), including necrosis, decreased sensation, and
      inability to breastfeed. The superomedial pedicle (SMP) reduction mammoplasty
      technique has been demonstrated as a safe and effective method of reduction in
      cases of mild to moderate hypertrophy. The aim of this study was to determine the
      risks of SMP in patients with gigantomastia (resection weight >1000 g/breast) at
      our institution. METHODS/TECHNIQUE: A retrospective study of all patients who
      underwent reduction mammoplasty with SMP technique by 8 surgeons at a single
      institution between 1999 and 2011 was performed. Patient demographics,
      preoperative breast measurements, and perioperative data were analyzed. Exclusion
      criteria were a reduction mammoplasty specimen weight of less than 1000 g.
      RESULTS/COMPLICATIONS: Our results show that 200 of 1750 patients who underwent
      SMP during the study period met the criteria. The average age at the time of the
      reduction was 39 years. The average body mass index was 36 kg/m. The average
      sternal notch to nipple distance was 35.5 cm for the right breast and 35.6 cm for
      the left breast. Average breast resection weight was 1277 g for the right and
      1283 g for the left. Average NAC transposition was 11.25 cm for the right breast
      and 11.40 cm for the left breast. Twenty-one (10.5%) patients experienced partial
      necrosis of the NAC and 98% of the patients subjectively reported normal NAC
      sensation postoperatively. All patients exhibited good breast shape and
      projection postoperatively. CONCLUSIONS: Our study shows that SMP reduction
      mammoplasty in patients with gigantomastia is a safe and effective reduction
      mammoplasty technique and is associated with low risk for NAC necrosis with good
      breast shape.

PMID- 23542844
TI  - Logistics of building a laser practice for the treatment of hypertrophic burn
      scars.
AB  - INTRODUCTION: Although lasers can improve burn scars, such treatment has not been
      adopted universally, due to operational challenges starting a practice and the
      perception that such a program is not financially viable. We report the logistics
      of building a laser practice for the treatment of hypertrophic burn scars.
      METHODS: We analyzed the clinical, operational, and financial components of our
      laser practice, focusing on treatment of hypertrophic burn scars, using pulsed
      dye laser, fractional CO2 laser, and intense pulsed light. Cases were performed
      in an operating room, with anesthesia, after preauthorization. We examined
      professional charges and collections, case time, variable and indirect expenses,
      and breakeven volumes. RESULTS: Our practice grew as follows: 2008, 1 case; 2009,
      44 cases; 2010, 169 cases; and 2011, 415 cases. Overall collection rate was
      32.1%. Expenses incurred by the provider, per 8-hour session, included laser
      rental/lease ($2375), personnel salaries ($1900), and physician overhead ($808),
      for a total cost of $5083. Mean charge was $1642 per case; mean collection was
      $527 per case. Median case time (procedure plus turnover) was 40 minutes. In this
      model, breakeven volume is 9.7 cases per day; breakeven time is 49.7 minutes.
      Provider profit margin for 10 cases per day, or 83% capacity utilization, is $187
      per day (income - expenses = $5270 - $5083). CONCLUSIONS: Despite high costs
      associated with starting and operating a laser practice for the treatment of
      hypertrophic burn scars, a sustainable enterprise can be achieved when the
      provider has accrued enough volume to batch cases over an entire day. Critical to
      achieving breakeven is preauthorization, controlling overhead, and efficient
      throughput.

PMID- 23542845
TI  - Autologous fat transfer in aesthetic facial recontouring.
AB  - Autologous fat graft transplantation has become increasingly popular in recent
      years. The recognition that soft tissue volume loss contributes to the aging of
      the face has driven the use of this procedure. Tumescent lipoaspirate provides
      ready accessibility of tissue for this transplantation, despite some perceived
      deficiencies in the predictability of volume maintenance with this method. We
      report our experience with immediately processed sedimented fat transfer for
      facial grooves and volume correction. A retrospective review of a consecutive
      series of 75 autologous fat transfers from October 2008 to July 2011 in 8 female
      patients between ages 46 and 73 years was conducted at Georgia Health Sciences
      University. The grafting was performed to improve facial aesthetic contours.
      Twenty-two were performed for correction of grooves and creases: 12 for
      nasolabial fold, 4 glabella, and 6 nasojugal. Fifty-three transfers were
      performed for volume augmentation: 17 malar, 14 submalar, 11 lip, 8 temple, 2
      chin, and 1 jowl. A tumescent technique with manual syringe harvest was used. The
      abdomen was the most frequently used donor site. The tumescent was decanted from
      the lipoaspirate. Oil and nonviable fat were excluded. Care was taken to reduce
      the time from harvest to transplantation, with no syringe transfers, minimizing
      potential oxidation and injury of the tissue. The mean volume of fat transferred
      was 24 mL (range, 4-54 mL). Mean follow-up was 25 months (range, 6-36 months). A
      second session of fat transfer was required in a small percentage. Complications
      included minor asymmetry in 1 patient (resolved with graft manipulation) and
      prolonged swelling in another. No postoperative cellulitis or fat necrosis was
      reported. Clinical evaluations and patients reported a satisfactory result 88% of
      the time. Patients universally reported (100%) a desire to have the procedure
      performed again. Autologous fat transfer for facial soft tissue contouring is
      simple, safe, inexpensive, and effective. Its ready availability, natural
      integration into host tissues, and potentially permanent correction make it
      particularly useful for this application. All patients were satisfied with the
      soft, natural appearance.

PMID- 23542846
TI  - Prospective, before-after cohort study to assess the efficacy of laser therapy on
      hypertrophic burn scars.
AB  - INTRODUCTION: Hypertrophic burn scars produce significant morbidity, including
      itching, pain, stiffness, and contracture. Best practices for management continue
      to evolve. Lasers have recently been added to treatment algorithms, but
      indications and efficacy have not been fully defined. We studied the impact of
      laser therapies on hypertrophic burn scars. METHODS: We conducted a prospective,
      before-after study in burn patients with hypertrophic scars. Procedures were
      performed more than 6 months after burn injury and were repeated monthly. The
      pulsed-dye laser was used for pruritus and erythema, whereas the fractional CO2
      laser was used for stiffness and abnormal texture. All procedures were performed
      in the OR, with anesthesia. Outcomes are as follows: (1) Vancouver Scar Scale
      (objective changes in pigmentation, erythema, pliability, height; range, 0-15)
      and (2) UNC Scar Scale (subjective changes in pain, itching, tingling, stiffness;
      range, 0-12). Before-after scores were compared by Student t test, with
      significance assigned to P values of <0.05. RESULTS: During 2011, we treated 147
      patients (mean age, 26.9 years; mean TBSA, 16.1%) over 415 sessions (2.8
      sessions/patient), including pulsed dye laser (n = 327) and CO2 (n = 139), mean
      surface area of 83 cm. Etiology included flame (75), scald (37), and other (35).
      Treatments occurred 16 months (median) and 48 months (mean) after burn injury.
      Vancouver Scar Scale decreased from 10.4 (SD, 2.4) to 5.2 (1.9) (P < 0.0001). UNC
      Scar Scale decreased from 5.4 (2.5) to 2.1 (1.7) (P < 0.0001). Mean length of
      follow-up was 4.7 months. CONCLUSIONS: Laser therapies significantly improve both
      the signs and symptoms of hypertrophic burn scars, as measured by objective and
      subjective instruments.

PMID- 23542847
TI  - Incidence and management of adverse events after the use of laser therapies for
      the treatment of hypertrophic burn scars.
AB  - INTRODUCTION: Hypertrophic burn scars may generate significant morbidity, due to
      intense pruritus, persistent dysesthesias, and contracture. Although treatment
      with pulsed dye laser and fractional CO2 laser may improve symptoms, incidence of
      secondary wound complications is not well known. We examined the adverse event
      profile of laser therapies for the treatment of hypertrophic burn scars. METHODS:
      We performed a descriptive, retrospective, 6-month study of all patients who
      underwent laser therapies, at an accredited regional burn center, to improve the
      vascularity, texture, thickness, and stiffness of symptomatic burn scars. Data
      regarding skin type, mechanism, area treated, and laser parameters were
      collected. Main outcome measures included pigmentation changes, blistering, rash,
      infection. chi analysis and Student t test were used to evaluate associations
      between variables. RESULTS: A total of 95 patients underwent 163 treatment
      sessions (mean, 2.7 sessions/patient) with pulsed dye laser (71%), CO2 laser
      (22%), and other lasers (7%). Forty-one adverse events were recorded:
      hyperpigmentation (2%), hypopigmentation (12%), mild blistering (27%), pain
      (37%), rash (7%), fever (10%), and infection (2%). Patients with scald burns were
      more likely to develop blistering, rash, and fever after treatment (all P <
      0.05). Higher Fitzpatrick skin type was associated with hypopigmentation and
      blistering, whereas CO2 laser was associated with increased postoperative pain
      (all P < 0.05) CONCLUSIONS: Despite the frequent occurrence of pain and mild
      blistering after laser treatment of hypertrophic burn scars, major adverse
      effects were exceedingly rare, with improvement noted in all patients. Patients
      with higher Fitzpatrick skin types must be handled with care, to avoid
      complications of blistering and hypopigmentation.

PMID- 23542848
TI  - Classification and management of seromas in immediate breast reconstruction using
      the tissue expander and acellular dermal matrix technique.
AB  - Tissue expander (TE)/acellular dermal matrix (ADM)-based breast reconstruction
      used in immediate postmastectomy breast reconstruction, although a popular
      technique, is not without complications.Although seroma formation is recognized
      and reported in the literature as a complication, little information addresses
      seroma(s) management. We conducted a retrospective review of 100 consecutive
      TE/ADM immediate reconstructions during a 2-year period, performed by a single
      surgeon. Data collection included patient demographics, adjuvant therapy, initial
      TE fill volume, time to completion of expansion, seroma formation, management of
      seroma, and wound complications, up to the time of definitive implant exchange.
      From December 2009 to December 2011, 67 patients (100 reconstructions) underwent
      TE/ADM immediate breast reconstruction. Thirty-one reconstructions were
      identified having clinically significant seroma(s). Eighteen of the
      reconstructions required multiple drainage procedures. With these data, a 3-group
      classification system was created based on the number of aspirations. In review
      of the 3 groups, 71% of group III required either Seroma-Cath or operative
      drainage beyond simple aspiration(s). Of the 100 reconstructions, 3 (3%) ended in
      TE explantation. Only 1 (3%) TE explantation, interestingly from group I, was
      attributable to seroma formation. Using the data, we devised a management
      strategy emphasizing attentiveness to seroma formation, recognition, and
      treatment. Seroma formation is a known entity linked to complications in TE/ADM
      reconstructive course. A seroma classification system and treatment algorithm is
      offered to minimize abandonment of the reconstruction and optimize outcomes.

PMID- 23542849
TI  - Use of osteogenesis distractors in cloverleaf skull reconstruction.
AB  - Cloverleaf skull deformity (Kleeblattschadel-Syndromen, trilobular skulls)
      results from synostosis of multiple cranial sutures. The number of sutures
      involved, the pathogenesis of the synostosis, and the associated anomalies and
      syndromes are variable. All forms of cloverleaf skull are associated with a high
      morbidity and mortality. Management of surviving infants requires multiple
      decompressive and reconstructive operative procedures. Maximal advancement of the
      forehead/brow at the initial surgery is usually not enough to correct the
      associated proptosis and a second brow advancement must be done. We present a
      patient with Apert syndrome and cloverleaf skull deformity that required early (1
      month old) cranial vault decompression due to severe proptosis and papilledema.
      Our management included the placement of osteogenesis distracters on the
      forehead/brow to gain additional advancement and expand the soft tissue.

PMID- 23542850
TI  - Safety of antiadhesion barriers in hand surgery.
AB  - INTRODUCTION: Adhesions are a major cause of complications and need for repeat
      surgery in the hand and wrist. They are indication for tenolysis and cause
      prolonged need for therapy and inability to regain full hand motion. Minimizing
      adhesions in the hand and wrist would greatly improve surgery, by decreasing cost
      as well as improved outcome and postoperative function. Antiadhesion barriers,
      products consisting of hyaluronic acid and methylcellulose were originally
      advocated for its use in the peritoneal cavity for prevention of adhesions
      initially by gynecologist, then general, trauma, and colorectal surgeons.
      Recently, several authors have looked at its use in animals for prevention of
      adhesions in regard to tendons, in particular in chickens and rabbits. However,
      no human studies exist in the literature that shows statistical efficacy or
      discussing its safety. METHODS: All cases of tendon repairs in the hand and wrist
      from January 2009 to January 2012 with an antiadhesion barrier placed by a single
      plastic/hand surgeon at our medical center were evaluated for complications and
      outcomes. Fourteen patients were identified over this period; demographic data
      and comorbidities were examined.All patients were placed in blocking splints
      postoperatively and discharged with 5 days of antibiotics. RESULTS: Of the 14
      patients identified over this period, 1 was female and 13 were male. Age of
      patients ranged from 13 to 74 years. Comorbidities evaluated included diabetes,
      hypertension, previous wrist or hand injuries or surgery, arthritis, and tobacco
      use. There was 1 postoperative wound infection with minimal wound separation
      which resolved with oral antibiotics and Xeroform dressing. One patient
      experienced spastic muscle disease leading to rerupture of tendon repair.
      Remainder of patients did not experience any wound complications. No patients
      required tenolysis after use of the antiadhesion barriers. CONCLUSIONS:
      Antiadhesion barriers are safe to use in humans for hand/wrist surgery. Studies
      to evaluate efficacy will require larger numbers of patients, but have already
      begun at our medical center. According to data from animal studies, antiadhesion
      barriers should serve as a useful tool for the decrease or even prevention of
      adhesion formation in the wrist and hand.

PMID- 23542851
TI  - Factors affecting complications in radiated breast reconstruction.
AB  - INTRODUCTION: Breast irradiation in combination with breast reconstruction is
      associated with increased complications. Because of the diminishing threshold for
      radiotherapy, breast reconstruction irradiation is rising. Our aim was to
      evaluate factors affecting outcomes in irradiated breast reconstructions.
      METHODS: A review of consecutive patients who underwent mastectomy, radiation,
      and breast reconstruction was conducted. Patient demographics, operative
      procedure, breast irradiation timing, and postoperative complications were
      collected. RESULTS: One hundred fifty-four patients (157 breast reconstructions)
      were included with a mean follow-up of 6 years. Average age at reconstruction was
      50 years. One hundred nine cases were immediate and 48 cases were delayed. Sixty
      eight cases were autologous reconstructions and 89 cases were implant-based.
      Thirty-seven cases used acellular dermal matrices (ADMs); 60% of cases were
      radiated before reconstruction and 40% were radiated afterward. Major
      complications occurred in 43% of patients and minor complications occurred in
      17%. The presence of ADM led to an increase in complication rate with a 2.3-fold
      greater chance of requiring reoperation (P = 0.03). No significant difference in
      complication rates was associated with presence of hypertension, diabetes,
      smoking, elevated body mass index, autologous versus implant-based
      reconstructions, delayed versus immediate reconstructions, and time between
      radiation and reconstruction. CONCLUSIONS: Radiation after prosthetic
      reconstruction may produce an increase in failure rates. The use of ADMs in the
      face of breast irradiation increases the likelihood of a complication requiring
      reoperation.

PMID- 23542852
TI  - A classification system for fat necrosis in autologous breast reconstruction.
AB  - PURPOSE: Fat necrosis (FN) is a common complication of autologous breast
      reconstruction, yet no classification system exists to describe it. We sought to
      develop and validate a tool for meaningful reporting, comparison of techniques,
      and treatment planning. Our hypothesis was that a valid classification system
      would demonstrate higher grades of FN for pedicled transverse rectus abdominus
      myocutaneous (pTRAM) flaps as compared to free flaps (FF). METHODS: A
      classification system for FN was developed: grade I, radiologic evidence only;
      grade II, palpable but not visible FN; grade III, palpable and visible FN; and
      grade IV, symptomatic FN. For validation, we applied this system to patients who
      had undergone pTRAM flaps from 2002 to 2006 and FF from 2006 to 2010 at our
      institution. RESULTS: We performed 93 pTRAM flaps in 69 patients and 102 FF in 69
      patients. One patient had grade I FN and was observed. Of the 29 patients with
      grade II FN, 48% were observed, 17% had biopsy, and 35% underwent debridement. Of
      the 9 patients with grade III FN, 11% underwent biopsy and 89% had debridement.
      All patients with grade IV FN underwent debridement. The distribution of FN
      differed between pTRAM and FF. The mean FN grade for patients undergoing pTRAM
      was 1.4 versus 0.4 for those undergoing FF (P < 0.05). Fat necrosis requiring
      reoperation was more frequent in the pTRAM group (23.7% vs 5.9%, P < 0.05).
      CONCLUSIONS: Our validation study confirmed that FN grade was associated with the
      need for surgery and was higher for pedicled flaps as compared to FFs. As it is
      similar to the Baker grading system for capsular contracture, this classification
      system is familiar to all plastic surgeons. It is simple, easy to remember,
      clinically oriented, and could be readily incorporated into outcome studies of
      autologous breast reconstruction.

PMID- 23542853
TI  - Bilateral accessory breast tissue of the vulva: a case report introducing a novel
      labiaplasty technique.
AB  - INTRODUCTION: We present the case of a 23-year-old female with bilateral ectopic
      breast tissue of the vulva, the repair of which necessitated a novel labiaplasty
      technique. Labiaplasty is becoming an increasingly frequent cosmetic procedure,
      and the popularity of brief didactic labiaplasty courses has risen in response to
      consumer demand. There is a paucity of detailed anatomic description of female
      sensory innervation patterns to the clitoris and surrounding structures. This
      places patients at risk for denervation of clitoral structures during labiaplasty
      procedures. Our novel technique proposes a method of individualized patient
      neurosensory mapping preoperatively, which allows for surgical planning to avoid
      injury to the sensory branches of the dorsal clitoral nerve. METHODS: A 23-year
      old female presented with bilateral vulvar masses that involved the clitoral
      complex, which had first become apparent during the second trimester of
      pregnancy, and failed to resolve in the postpartum period. We describe the
      preoperative planning and intraoperative approach and dissection to labiaplasty
      in this patient, which was complex given the size of the masses, and specifically
      designed to avoid injury to sensory branches of the dorsal clitoral nerve.
      DISCUSSION: As labiaplasty becomes more common, it is important to approach
      labiaplasty patients with a detailed understanding of the sensory innervation of
      the clitoris and surrounding structures, to avoid nerve injury and resultant
      sexual dysfunction. Traditional labiaplasty approaches may violate the sensory
      innervation patterns of the clitoral region, thus causing a sensory loss that
      affects patient sexual function. Our novel approach to preoperative clitoral
      nerve sensory mapping provides an alternative method of labiaplasty that may
      avoid denervation injury.

PMID- 23542854
TI  - Elevation: developing a mentorship model to raise the next generation of plastic
      surgery professionals.
AB  - PURPOSE: To elucidate the components of professionalism specific to plastic
      surgery, we surveyed surgeons, anesthesiologists, and fourth-year medical
      students at a public university. We sought to define the central components of
      professionalism in plastic surgery, to determine the difference in perception of
      professionalism by plastic surgeons (PSs), compared to other practitioners (OPs),
      and to improve education in professionalism by obtaining data on attitudes of
      professionalism among practitioners. METHODS: Using SurveyMonkey, we distributed
      a questionnaire to members of the Departments of Surgery and Anesthesia and
      fourth-year medical students. The responses of PSs (n = 22) were compared to non
      plastic surgeons (OPs, n = 294). RESULTS: Of the 594 participants, 316 completed
      the survey (response rate, 53%). Participants consisted of 211 (66.8%) medical
      students, 60 (19%) residents, 5 (1.6%) fellows, 28 (8.9%) attending physicians, 6
      (1.9%) nonphysician providers, and 6 (1.9%) administrators. Both PS and OP listed
      "the development and conformance to a body of ethics" the most important
      component of professionalism. Most participants thought that professionalism
      could be taught, and assessed. Plastic surgeons listed "not enough mentors"
      (63.2%) as the main obstacle to teaching professionalism, whereas OP listed "not
      a priority in medical school curriculum" (48.2%). Both PS and OP cited substance
      abuse, fraud, and sexual misconduct as egregious displays of unprofessional
      behavior. Opinions differed between the groups, regarding aspects of
      professionalism pertaining to plastic surgery. When asked about "charity raffles"
      for cosmetic surgery, 72.2% of PS ranked this as a 4 or 5 (with 5 representing
      the most unprofessional behavior), compared to only 46.7% of OP who assigned this
      a 4 or 5. For the scenario of a PS deceiving patients, by showing them another
      surgeon's before and after photographs, 84.2% of PS assigned this a 4 or 5,
      whereas 71.0% of OP ranked this a 4 or 5. Both groups cited working while
      impaired with alcohol as the most egregious example of unprofessional behavior.
      CONCLUSIONS: The opinions of PSs mirror those of their colleagues, regarding
      general components of professionalism. However, PSs are more conservative and
      cautious than their peers, perhaps due to successful educational efforts in
      mentoring, training, and maintenance of certification.

PMID- 23542855
TI  - Effects of connective tissue growth factor on the regulation of elastogenesis in
      human umbilical cord-derived mesenchymal stem cells.
AB  - BACKGROUND: A key to clinical microtia reconstruction is construct flexibility.
      The most significant current limitation to engineered elastic cartilage is
      maintaining an elastic phenotype, which is principally dependent on elastin
      production (although other parameters, including maintenance of a ratio above 1
      for collagens II to I, minimizing collagen X content, and presence of adequate
      matrix fibrillin for elastin binding, all play supporting roles). Connective
      tissue growth factor (CTGF), a compound secreted by chondrocytes, has been shown
      to promote an elastic phenotype in mature rabbit chondrocytes; however, CTGF
      effect on undifferentiated mesenchymal stem cells (MSCs) has not been
      characterized. The principal aim of this study is to analyze CTGF effect on
      elastin production in umbilical cord (UC)-derived MSCs and to determine optimal
      timing of treatment to maximize elastin production. METHODS: Human UCMSCs
      (hUCMSCs) were isolated from Wharton jelly using an explant technique, grown to
      passage 3, seeded onto nanofiber scaffolds, and chondroinduced for 21 days.
      Nanofiber scaffolds were electrospun using solubilized poly L-lactide/D
      lactide/glycolide (PLGA). Chondrogenic media was supplemented with 25 MUg/mL CTGF
      starting at day 0 or 7. Messenger RNA (mRNA) for Collagen I, II, X, fibrillin,
      and elastin was quantified by RT-PCR; glycosaminoglycan (GAG) matrix deposition
      was assessed and normalized by cellular DNA content. Elastin protein was assessed
      by Western blot analysis. All experiments were performed in triplicate with MSCs
      from 4 distinct cords. Multiway analysis of variance with Newman-Keuls post test
      was used to determine statistical significance. RESULTS: Connective tissue growth
      factor treatment results in increased GAG/DNA ratio; the differentiation index
      was maintained above 1 in all conditions, with increased collage II noted at days
      7 and 14 in CTGF conditions; no difference in collagen X or fibrillin mRNA was
      noted. Increased elastin mRNA and protein were noted at day 14 in conditions
      treated with CTGF at day 7 after differentiation. CONCLUSIONS: Connective tissue
      growth factor leads to maximal elastin increase in UCMSCs after 7 days of
      chondroinduction and not in undifferentiated MSCs. With appropriately timed
      treatment, CTGF may be a useful adjunct in maintaining an elastic cartilage
      phenotype in engineered cartilage from human UCMSCs.

PMID- 23542856
TI  - Comparison of sterile versus nonsterile acellular dermal matrices for breast
      reconstruction.
AB  - BACKGROUND: Acellular dermal matrix (ADM) has been associated with an increased
      incidence of complications after implant-based breast reconstruction. Recently,
      sterile ADM has been introduced in an attempt to minimize these complications. To
      analyze the impact of this product on patient outcomes, we created a database of
      patients undergoing implant-based breast reconstruction. METHODS: Patients
      undergoing implant-based breast reconstruction at the University of Kentucky
      Medical Center from January 1, 2011, to December 31, 2011 were identified. A
      database of patient characteristics and outcomes was created. Outcomes
      investigated included mastectomy flap necrosis, dehiscence, infection, red
      breast, capsular contracture, hematoma, and seroma. Statistical analysis was
      performed. RESULTS: Fifty-eight patients underwent breast reconstruction with
      implants or tissue expanders. Of the 58 patients, 9 had the sterile form of ADM
      placed, 25 had the original aseptic but not sterile ADM, and 24 were not
      reconstructed with ADM. The most frequent complication noted was seroma,
      occurring in 6/9 patients with sterile ADM as compared to 2/25 with the aseptic
      ADM. This was statistically significant (P = 0.003). CONCLUSIONS: The use of
      sterile ADM is associated with a statistically significant increase in seroma
      formation. The etiology of this increased incidence remains unknown, but it
      correlates with the introduction of the sterile form of ADM at our institution. A
      different preparation or sterilization process, or some other variable as yet
      unknown, may be responsible. Further studies comparing the different forms of ADM
      in an animal model may serve to clarify this issue.

PMID- 23542857
TI  - Changes in airflow dynamics after creation of pharyngeal flaps in nonsyndromic
      children.
AB  - Velopharyngeal insufficiency is a common problem in the cleft palate population
      that may require a pharyngeal flap. Sleep disordered breathing is a common
      complication of this surgery and a baseline sleep study is often performed before
      undergoing the procedure. Few postoperative sleep studies are ever done and
      little is known about the effects that pharyngeal flaps have on airflow
      dynamics.Preoperative and postoperative nasometry and polysomnographic data were
      reviewed and compared from nonsyndromic children requiring pharyngeal flap since
      2009. Eighteen children having undergone pharyngeal flap were identified. Of
      those 18, Nadir oxygen saturations were worsened in 10, improved in 7, and
      remained the same in 1. Snoring was caused or made worse in 8. Sleep efficiency
      was worse in 11, improved in 6, and remained the same in 1. Apnea/hypopnea events
      increased in 9 and decreased in the other 9. Hypernasality was improved in
      varying degrees in 17 patients, but all required additional speech therapy.
      Diagnosed preoperative sleep apnea remained in 1 patient. No patient's
      postpharyngeal flap had any significant sleep disturbance that would warrant
      continuous positive airway pressure. No flaps required division or takedown.This
      preliminary study suggests that pharyngeal flaps may increase snoring and
      apnea/hypopnea events without causing diagnosable sleep disordered breathing and
      the resultant clinical sequelae. Nasometry shows evidence of nasal airway
      diversion without complete obstruction. Speech improves more subjectively than
      nasometry would predict after pharyngeal flap.

PMID- 23542858
TI  - Time to completion of nipple reconstruction: what factors are involved?
AB  - BACKGROUND: Nipple reconstruction is often used as a marker for completion of the
      breast reconstructive process. The purpose of this study was to determine the
      average time to nipple reconstruction and the factors that influence this
      process. METHODS: All patients who underwent postmastectomy breast reconstruction
      at Emory University between 2005 and 2011 were reviewed. Only those who had
      completed nipple reconstruction were included. Variables recorded were body mass
      index, age, smoking history, surgeon, presence of preoperative or postoperative
      chemotherapy or radiation therapy, type of reconstruction, timing of
      reconstruction, unilateral or bilateral reconstruction, and complication history.
      Time to completion of nipple reconstruction was calculated and comparisons were
      made. RESULTS: A total of 451 patients completed nipple reconstruction (128
      implant reconstructions, 120 latissimus plus implant reconstructions, 23
      latissimus only reconstructions, and 180 transverse rectus abdominus myocutaneous
      flap [TRAM] or deep inferior epigastric perforator flap [DIEP] reconstructions).
      Average time to nipple reconstruction was 12.25 months. Patients who underwent
      TRAM or DIEP flaps completed reconstruction on average earlier than implant-based
      reconstruction and latissimus-only reconstruction (8.67 vs 11.2 and 11.3 months,
      respectively, P = 0.0016). Patients who underwent postoperative chemotherapy or
      radiation therapy were delayed compared to those that did not (11.3 vs 9.33 and
      13.87 vs 9.87 months, P = 0.0315 and P = 0.0052). Timing of completion was also
      dependent on attending surgeon (9.8 and 11.43 months for the 2 senior surgeons, P
      = 0.0135) and presence of complications (10.3 compared to 9.77 months for
      patients without complications, P = 0.0334). Body mass index, smoking history,
      preoperative chemotherapy or radiation therapy, timing of reconstruction, and
      unilateral versus bilateral reconstruction did not affect time to nipple
      reconstruction. CONCLUSIONS: Type of reconstruction, surgeon, presence of
      complications, and need for postoperative chemotherapy or radiation therapy all
      affect timing to completion of breast reconstruction. Patients should be
      counseled as to these factors at the initial consultation to set appropriate
      expectations.

PMID- 23542859
TI  - Patient motivations for choosing postmastectomy breast reconstruction.
AB  - INTRODUCTION: The number of women who undergo postmastectomy breast
      reconstruction is reported to be around 40% and, although increased from previous
      decades, seems lower than expected. The purpose of this report is to investigate
      and improve our understanding of women's motivations for choosing reconstruction.
      METHODS: We prospectively surveyed consecutive patients referred for possible
      reconstructive surgery at Emory University Hospital between December 2008 and
      September 2010. A Likert-scale (1-5) questionnaire was used evaluating body
      image, femininity and sexuality, and influences regarding reconstruction.
      Demographic information was collected and analyzed. A PubMed search was also
      performed evaluating national rates of reconstruction, the demographic
      disparities, and the decision-making process behind undergoing reconstruction.
      RESULTS: Among the 155 women surveyed, most (63%, n = 99) were 40 to 60 years
      old, 54.8% (n = 85) were African American, and 41.3% (n = 64) were white.
      Overall, patients agreed more strongly with questions related to body image as a
      motivating factor for breast reconstruction than they did with questions related
      to sexuality or femininity (mean score, 2.85 vs 3.26). When asked about their
      primary motivation for breast reconstruction, 76% of women agreed it was to
      maintain a balanced appearance, 34% agreed it was to continue to feel feminine,
      and 7.7% agreed it was to maintain sexual functioning. When asked about outside
      influences in pursuing breast reconstruction, the 51.6% of patients reported that
      they were urged by their referring physician to consider it, and most of the
      patients (58%) discussed the surgery with other breast cancer patients
      considering breast reconstruction. CONCLUSIONS: Women pursuing breast
      reconstruction are motivated more by concerns of body image than issues of
      sexuality or femininity, which is independent of any demographic characteristics.
      It is important for referring physicians to recognize their role in initiating
      the discussion on reconstruction, and women would benefit from being referred to
      support groups to discuss their treatment and reconstruction with other breast
      cancer patients.

PMID- 23542860
TI  - Minimizing donor-site morbidity following bilateral pedicled TRAM breast
      reconstruction with the double mesh fold over technique.
AB  - INTRODUCTION: Transverse rectus abdominus muscle flaps (TRAM) can result in
      significant abdominal wall donor-site morbidity. We present our experience with
      bilateral pedicle TRAM breast reconstruction using a double-layered polypropylene
      mesh fold over technique to repair the rectus fascia. METHODS: A retrospective
      study was performed that included patients with bilateral pedicle TRAM breast
      reconstruction and abdominal reconstruction using a double-layered polypropylene
      mesh fold over technique. RESULTS: Thirty-five patients met the study criteria
      with a mean age of 49 years old and mean follow-up of 7.4 years. There were no
      instances of abdominal hernia and only 2 cases (5.7%) of abdominal bulge. Other
      abdominal complications included partial umbilical necrosis (14.3%), seroma
      (11.4%), partial wound dehiscence (8.6%), abdominal weakness (5.7%), abdominal
      laxity (2.9%), and hematoma (2.9%). CONCLUSIONS: The TRAM flap is a reliable
      option for bilateral autologous breast reconstruction. Using the double mesh
      repair of the abdominal wall can reduce instances of an abdominal bulge and
      hernia.

PMID- 23542861
TI  - Safety and efficacy of outpatient lower body lifting.
AB  - BACKGROUND: The lower body lift (LBL) is a comprehensive body contouring
      procedure done after massive weight loss. Because of the magnitude of the
      operation and demands of subsequent care, it has traditionally been viewed as an
      inpatient procedure. However, it is believed that with surgical experience
      combined with fine tuning of perioperative and postoperative care, lower body
      lifting is safe as an outpatient in properly selected patients. METHODS: In this
      article, we retrospectively review and evaluate our series of 35 patients (19
      outpatient and 16 inpatient), who have undergone lower body lifting after massive
      weight loss. Operative technique, perioperative management, and postoperative
      care are reviewed. RESULTS: Compared to the inpatients, the body mass index of
      the outpatients was significantly less: 24.99 compared to 30.89 kg/m,
      respectively (P = 0.002 chi value 7.886). Reoperations did not occur in any of
      the 19 outpatient LBL procedures, but were necessary in 6 of the 16 inpatients,
      all for wound closure (P < 0.001 chi value 25.811). No patient in either group
      had thromboembolic occurrences, clinically apparent hematomas, and none required
      transfusions. CONCLUSIONS: Outpatient LBL is safe and effective when performed on
      the properly selected patient. Avoidance of hospitalization has importance in
      minimizing nosocomial infections or other complications. There is also potential
      great influence on access to care due to reduced costs associated with outpatient
      surgery centers, compared to hospitals. As such, a financial barrier is
      alleviated to many who cannot otherwise afford these procedures after weight
      loss.

PMID- 23542862
TI  - Radical surgical resection combined with lymphadenectomy-directed antimicrobial
      therapy yielding cure of severe axillary hidradenitis.
AB  - BACKGROUND: The current gold standard therapy for hidradenitis suppurativa (HS)
      is surgical resection. However, despite complete resection, the reoperation rate
      is reported as high as 54% due to wound infections and disease recurrences. Our
      hypothesis is that this high recurrence rate is related to retained disease and
      infected tissue not included in soft tissue resection, namely the lymph nodes.
      Therefore, performing a superficial lymphadenectomy with nodal microbacterial
      analysis would remove all infected tissue, eradicate the disease, and allow more
      specific targeted antibiotic therapy. METHODS: From 2004 to 2009, 11 patients
      underwent 15 wide en bloc resections including superficial lymphadenectomy with
      flap reconstruction for axillary HS. A retrospective review was performed with
      the following outcomes assessed: culture results, hospital stay, and recurrences
      of HS. RESULTS: Patients were followed up for an average of 4.3 years. During
      this time, there were no wound complications or disease recurrences. Positive
      bacterial cultures occurred in 12 of 14 nodes with results that differed from the
      soft tissue purulence. This led to a 75% change in antibiotic regimen.
      Superficial abscess cultures were uniformly covered, whereas only 3 of 12 nodal
      cultures where sensitive to our empiric antibiotic coverage. No patients
      developed lymphedema or any loss of function in the involved upper extremity.
      CONCLUSIONS: Axillary HS has traditionally been a challenge due to the morbidity
      of care and high recurrence. Our data show that an en bloc resection with a
      superficial lymphadenectomy and subsequent antimicrobial therapy based on both
      the soft tissue and the lymph nodes can provide a definitive cure.

PMID- 23542863
TI  - Annals of Plastic Surgery SESPRS issue introduction.

PMID- 23542864
TI  - Is hippocampal volume a good marker to differentiate Alzheimer's disease from
      frontotemporal dementia?
AB  - BACKGROUND: Previous studies analyzed the ability of hippocampal volumes (HV) to
      differentiate Alzheimer's disease (AD) from frontotemporal dementia (FTD).
      However, these studies did not include patients selected according to clinico
      biological criteria, using pathophysiological biomarkers. OBJECTIVE: To analyze
      the effectiveness of hippocampal volumetric measures to distinguish AD from
      behavioral variant FTD (bvFTD), using strict inclusion criteria based on clinical
      and pathophysiological markers. METHODS: Seventy-two participants were included:
      31 AD patients with predominant and progressive episodic memory deficits
      associated with typical AD cerebrospinal fluid (CSF) profile and/or positive
      amyloid imaging (PET with 11C-labeled Pittsburgh Compound B [PiB]), 26 bvFTD
      patients diagnosed according to consensual clinical criteria and with no AD CSF
      profile, and 15 healthy controls without amyloid retention on PiB-PET exam. HV
      were segmented with an automated method and were normalized to total intracranial
      volume (nHV). RESULTS: Significant reductions in HV were found in both AD and
      bvFTD patients compared with controls, but there were no significant difference
      between AD and bvFTD patients. Mean nHV distinguished normal controls from either
      AD or bvFTD with high sensitivity (80.6% and 76.9%, respectively) and specificity
      (93.3% for both), but it was inefficient in differentiating AD from bvFTD (9.7%
      specificity). There was no difference in the clinical and neuropsychological
      profiles according to HV in bvFTD and AD patients. CONCLUSIONS: When considered
      alone, measures of HV are not good markers to differentiate AD from bvFTD.
      Hippocampal sclerosis associated with FTD may explain the high degree of overlap
      in nHV between both groups.

PMID- 23542866
TI  - Amyloid-beta interacts with blood-brain barrier function in dementia: a
      systematic review.
AB  - To date, the exact pathogenesis of dementia is still unknown. The most frequently
      hypothesized initiating factor is an accumulation of the protein amyloid-beta in
      the brain, which has been associated with dementia of the Alzheimer type. Another
      potentially important initiating factor is a disrupted blood-brain barrier. This
      can initiate cerebral microangiopathy, which has frequently been associated with
      vascular dementia. Although amyloid-beta and blood-brain barrier dysfunction have
      both been associated with one particular type of dementia (Alzheimer's disease
      and vascular dementia, respectively), they co-exist in most demented patients. In
      fact, increasing evidence indicates that amyloid-beta and blood-brain barrier
      disruption may interact and facilitate each other in their effect on
      neurodegeneration. The present systematic analysis describes the available
      evidence for a significant interplay between amyloid-beta and blood-brain barrier
      function in dementia.

PMID- 23542865
TI  - Brain transit and ameliorative effects of intranasally delivered anti-amyloid
      beta oligomer antibody in 5XFAD mice.
AB  - Alzheimer's disease (AD) is a global health crisis with limited treatment
      options. Despite major advances in neurotherapeutics, poor brain penetration due
      to the blood-brain barrier continues to pose a big challenge in overcoming the
      access of therapeutics to the central nervous system. In that regard, the non
      invasive intranasal route of brain targeting is gaining considerable attention.
      The nasal mucosa offers a large surface area, rapid absorption, and avoidance of
      first-pass metabolism increasing drug bioavailability with less systemic side
      effects. Intranasal delivery is known to utilize olfactory, rostral migratory
      stream, and trigeminal routes to reach the brain. This investigation confirmed
      that intranasal delivery of oligomeric amyloid-beta antibody (NU4) utilized all
      three routes to enter the brain with a resident time of 96 hours post single
      bolus intranasal administration, and showed evidence of perikaryal and
      parenchymal uptake of NU4 in 5XFAD mouse brain, confirming the intranasal route
      as a non-invasive and efficient way of delivering therapeutics to the brain. In
      addition, this study demonstrated that intranasal delivery of NU4 antibody
      lowered cerebral amyloid-beta and improved spatial learning in 5XFAD mice.

PMID- 23542867
TI  - The pattern of diffusion parameter changes in Alzheimer's disease, identified by
      means of linked independent component analysis.
AB  - Several recent studies have indicated that white matter is affected in
      Alzheimer's disease (AD). Diffusion tensor imaging is a tool by which the white
      matter microstructure can be examined in vivo, and might offer a possibility for
      the identification of the pattern of white matter disintegration in AD. In the
      current analysis, we made use of a novel model-free analysis approach of linked
      independent component analysis to identify a motif of diffusion parameter
      alterations exemplifying AD. Analysis of the diffusion data of 16 AD patients and
      17 age-matched healthy subjects revealed six independent components, two of which
      demonstrated differences between the patients and controls. Component #0 was
      dominated by axial diffusivity, but significant alterations in fractional
      anisotropy and mean and radial diffusivity were also detected. Alterations were
      found in regions of crossing of major white matter pathways, such as forceps,
      corona radiate, and superior longitudinal fascicle, as well as medio-temporal
      white matter. These results lend support to the coexistence of white matter
      disintegration of the late myelinating associating fibers and wallerian
      degeneration-related disintegration, in accordance with the retrogenesis and
      wallerian degeneration hypothesis.

PMID- 23542868
TI  - Cognitive lifestyle in older persons: the population-based Sydney Memory and
      Ageing Study.
AB  - BACKGROUND: Cognitive lifestyle may be an important modifiable risk factor for
      dementia but has not yet been comprehensively studied in healthy elderly.
      OBJECTIVE: To examine gender- and lifespan-related differences in cognitive
      lifestyle in a population-based cohort. METHODS: 872 individuals from the second
      wave of the Sydney Memory and Ageing Study (MAS) cohort were invited to complete
      the Lifetime of Experiences Questionnaire (LEQ), a validated measure of cognitive
      lifestyle. Of 555 questionnaires returned (64%), 253 were excluded due to prior
      diagnosis of mild cognitive impairment, leaving n = 302 cognitively-intact elders
      (mean age 80.1 years, +/-SD 4.7, 40.1% men). RESULTS: Total LEQ was significantly
      higher in men (97.9 +/- 20.0) than women (90.0 +/- 24.5), resulting mainly from
      midlife LEQ differences. Men were more likely to have worked in managerial or
      professional jobs (73.8% versus 39.5% women), and twice as likely to have
      supervised large groups of workers. In late life, women were significantly more
      likely to be living alone (68.1% versus 25.4% men), but otherwise significantly
      more engaged in specific cognitive activities, including reading novels (72.3%
      versus 52.0% men) and incorporating volunteer work (31.9% versus 19.7% men) and
      socializing (59.0% versus 37.0% men) into their typical day. Over the adult
      lifespan, it was more common for men and women to transition between LEQ tertiles
      than remain the same. CONCLUSIONS: Cognitive lifestyle changes over the adult
      lifespan and exhibits a range of gender-based differences. While older women are
      more likely to be living alone they generally lead a more active current
      cognitive lifestyle.

PMID- 23542869
TI  - Muscle loading is necessary for the formation of a functional tendon enthesis.
AB  - Muscle forces are essential for skeletal patterning during development.
      Eliminating muscle forces, e.g., through paralysis, leads to bone and joint
      deformities. Botulinum toxin (BtxA)-induced paralysis of mouse rotator cuffs
      throughout postnatal development closely mimics neonatal brachial plexus palsy, a
      significant clinical condition in infants. In these mice, the tendon-to-bone
      attachment (i.e., the tendon enthesis) presents defects in mineral accumulation
      and fibrocartilage formation, presumably impairing the function of the tissue.
      The objective of the current study was to investigate the functional consequences
      of muscle unloading using BtxA on the developing supraspinatus tendon enthesis.
      We found that the maximum endurable load and stiffness of the supraspinatus
      tendon attachment decreased after four and eight weeks of post-natal BtxA-muscle
      unloading relative to controls. Tendon cross-sectional area was not significantly
      reduced by BtxA-unloading, while, strength, modulus, and toughness were decreased
      in the BtxA-unloaded group compared to controls, indicating a decrease in tissue
      quality. Polarized-light microscopy and Raman microprobe analysis were used to
      determine collagen fiber alignment and mineral characteristics, respectively, in
      the tendon enthesis that might contribute to the reduced biomechanical
      performance in BtxA-unloaded shoulders. Collagen fiber alignment was
      significantly reduced in BtxA-unloaded shoulders. The mineral-to-matrix ratio in
      mineralized fibrocartilage was not affected by loading. However, the
      crystallographic atomic order of the hydroxylapatite phase (a measure of
      crystallinity) was reduced and the amount of carbonate (substituting for
      phosphate) in the hydroxylapatite crystals was increased. Taken together, these
      micrometer-scale structural and compositional changes partly explain the observed
      decreases in the mechanical functionality of the tendon enthesis in the absence
      of muscle loading.

PMID- 23542870
TI  - Metre-long cell-laden microfibres exhibit tissue morphologies and functions.
AB  - Artificial reconstruction of fibre-shaped cellular constructs could greatly
      contribute to tissue assembly in vitro. Here we show that, by using a
      microfluidic device with double-coaxial laminar flow, metre-long core-shell
      hydrogel microfibres encapsulating ECM proteins and differentiated cells or
      somatic stem cells can be fabricated, and that the microfibres reconstitute
      intrinsic morphologies and functions of living tissues. We also show that these
      functional fibres can be assembled, by weaving and reeling, into macroscopic
      cellular structures with various spatial patterns. Moreover, fibres encapsulating
      primary pancreatic islet cells and transplanted through a microcatheter into the
      subrenal capsular space of diabetic mice normalized blood glucose concentrations
      for about two weeks. These microfibres may find use as templates for the
      reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood
      vessels or nerve networks in vivo.

PMID- 23542871
TI  - Single-ion BAB triblock copolymers as highly efficient electrolytes for lithium
      metal batteries.
AB  - Electrochemical energy storage is one of the main societal challenges of this
      century. The performances of classical lithium-ion technology based on liquid
      electrolytes have made great advances in the past two decades, but the intrinsic
      instability of liquid electrolytes results in safety issues. Solid polymer
      electrolytes would be a perfect solution to those safety issues, miniaturization
      and enhancement of energy density. However, as in liquids, the fraction of charge
      carried by lithium ions is small (<20%), limiting the power performances. Solid
      polymer electrolytes operate at 80  degrees C, resulting in poor mechanical
      properties and a limited electrochemical stability window. Here we describe a
      multifunctional single-ion polymer electrolyte based on polyanionic block
      copolymers comprising polystyrene segments. It overcomes most of the above
      limitations, with a lithium-ion transport number close to unity, excellent
      mechanical properties and an electrochemical stability window spanning 5 V versus
      Li(+)/Li. A prototype battery using this polyelectrolyte outperforms a
      conventional battery based on a polymer electrolyte.

PMID- 23542872
TI  - A retrospective survey of human hydatidosis based on hospital records during the
      period of 10 years.
AB  - Hydatid cyst is a parasitic infection that is widely seen endemically in the
      Middle East countries. We studied hydatid cyst pattern in hospitalized adult
      patients in our hospital from 2000 to 2010. In this study 89 patients, 50 females
      and 39 males who were diagnosed to have hydatid cyst were evaluated. The mean age
      of the patients was 37.3 and the mean hospital stay was 10.1 days. The main
      complaint was abdominal pain (66.2%). The most common localization of cysts was
      the liver and the most radiological method to diagnose the disease was
      ultrasonography followed by CT scan. Our recurrence rate was more than average.
      We had no mortality and did not find any serious postoperative complication. Safe
      surgery is a role for hydatid cysts.

PMID- 23542873
TI  - The HLA Class II Associations with Rheumatic Heart Disease in South Indian
      Patients: A Preliminary Study.
AB  - INTRODUCTION: Rheumatic heart disease (RHD) occurs in 30-45% of the patients with
      rheumatic fever (RF) and it leads to chronic valvular lesions. The human
      leukocyte antigen (HLA) might confer a susceptibility to RHD. The aim of the
      present study was to determine the prevalent HLA class II DR/DQ allelic types
      which were associated with rheumatic heart disease (RHD) in a small group of
      south Indian patients and to compare them with those in the control subjects.
      METHODS: A total of 23 patients who were diagnosed with RHD and 6 control samples
      were included in this study. A low resolution HLA Class II DR/DQ typing was
      performed on the blood samples by the PCR-SSP method. RESULTS AND CONCLUSION: The
      DRB3*01:01:02:01 allele showed a positive association with RHD, whereas the DQB1
      loci alleles did not show any significant association.

PMID- 23542874
TI  - Iatrogenic Cushing's Syndrome in an Infant.
AB  - A high potency, long acting and/or the extended use of oral corticosteroids,
      particularly in children, may cause suppression of the hypothalamo-pituitary
      adrenal axis. However, the iatrogenic Cushing's syndrome in the infantile age
      group is rare and only few patients have been reported to date in the literature.
      Here, we are reporting a case of iatrogenic Cushing's syndrome in a 5-month-old
      male child, whose parents brought him to the hospital for puffiness of the face
      and overweight.

PMID- 23542875
TI  - Selective tracing of auditory fibers in the avian embryonic vestibulocochlear
      nerve.
AB  - The embryonic chick is a widely used model for the study of peripheral and
      central ganglion cell projections. In the auditory system, selective labeling of
      auditory axons within the VIIIth cranial nerve would enhance the study of central
      auditory circuit development. This approach is challenging because multiple
      sensory organs of the inner ear contribute to the VIIIth nerve (1). Moreover,
      markers that reliably distinguish auditory versus vestibular groups of axons
      within the avian VIIIth nerve have yet to be identified. Auditory and vestibular
      pathways cannot be distinguished functionally in early embryos, as sensory-evoked
      responses are not present before the circuits are formed. Centrally projecting
      VIIIth nerve axons have been traced in some studies, but auditory axon labeling
      was accompanied by labeling from other VIIIth nerve components (2,3). Here, we
      describe a method for anterograde tracing from the acoustic ganglion to
      selectively label auditory axons within the developing VIIIth nerve. First, after
      partial dissection of the anterior cephalic region of an 8-day chick embryo
      immersed in oxygenated artificial cerebrospinal fluid, the cochlear duct is
      identified by anatomical landmarks. Next, a fine pulled glass micropipette is
      positioned to inject a small amount of rhodamine dextran amine into the duct and
      adjacent deep region where the acoustic ganglion cells are located. Within thirty
      minutes following the injection, auditory axons are traced centrally into the
      hindbrain and can later be visualized following histologic preparation. This
      method provides a useful tool for developmental studies of peripheral to central
      auditory circuit formation.

PMID- 23542876
TI  - Use of Triplex PCR for Rapid Detection of PVL and Differentiation of MRSA from
      Methicillin Resistant Coagulase Negative Staphylococci.
AB  - INTRODUCTION: Methicillin-Resistant Staphylococcus aureus (MRSA) has become a
      major public health problem in both hospitals and communities. Panton - Valentine
      Leucocidin (PVL) has been reported to be an important marker for the highly
      pathogenic community acquired S. aureus infections. A rapid detection of these
      MRSA is very important for its treatment. The specific detection of MRSA is
      always a problem due to the prevalence of methicillin resistance among the
      coagulase negative Staphylococci. Hence, this study was done to develop a rapid
      triplex PCR for the detection of PVL positive MRSA and for the simultaneous
      differentiation of MRSA from Coagulase Negative Staphylococci (CoNS). MATERIALS
      AND METHODS: We developed a triplex PCR for the specific detection of PVL
      positive Community Acquired (CA) - MRSA and for its simultaneous differentiation
      from the coagulase negative Staphylococci. We used PCR for targeting the fem A
      gene which is specific for S. aureus, mecA which is specific for methicillin
      resistance and luk - PV which is specific for the PVL toxin. The method was
      evaluated with a total of 100 clinical isolates of Staphylococcus spp. RESULTS:
      The triplex PCR was successfully standardized by using the reference strains and
      it was evaluated by using clinical strains. The method was found to be rapid,
      highly sensitive (100%), specific (99%) and cost effective. CONCLUSION: Triplex
      PCR can be used as a diagnostic tool for the detection of the highly pathogenic
      strains of CA-MRSA.

PMID- 23542877
TI  - The Role of GABAB Receptors in Morphine Self-Administration.
AB  - BACKGROUND: There is only little information about the effects of GABA receptors
      agonist and antagonist on morphine self-administration. Present study was
      designed to assess role of GABAB receptors in the regulation of morphine
      reinforced self-administration. METHODS: THIS STUDY WAS PERFORMED IN FOUR GROUPS
      OF RATS: (1) Saline group, which received saline in the self-administration
      session. (2) Morphine group, which received morphine in saline solution in the
      self-administration session. (3) Baclofen + Morphine group, which received both
      baclofen 20 min before self- administration test and morphine in the self
      administration session. (4) Phaclofen + Morphine group, which received both
      phaclofen 20 min before self- administration test and morphine in the self
      administration session. The number of lever pressing and self-infusion were
      recorded. RESULTS: Morphine significantly increased the number of active lever
      pressing dose dependently in self-administration session in comparative with
      saline group. Administration of baclofen, 20 min before morphine self
      administration produced significant decrease in the initiation of morphine self
      administration during all session. Conversely, pre-treatment of phaclofen
      increased the number of active lever pressing and self-infusion in this test.
      CONCLUSION: Our results indicated a short-term treatment by baclofen, reduced
      morphine-maintenance response in a dose-dependent manner, suggesting that GABAB
      receptor agonists could be useful for reversing the neuroadaptations related to
      opiates.

PMID- 23542878
TI  - Relationships between strength, sprint, and jump performance in well-trained
      youth soccer players.
AB  - Research has demonstrated a clear relationship between absolute and relative
      strength and sprint and jump performance in adult athletes; however, this
      relationship in younger athletes has been less extensively studied. The aim of
      this study, therefore, was to determine the relationships between strength,
      sprint, and jump performances in well-trained youth soccer players. Thirty-four
      young male soccer players (17.2 +/- 0.6 years; body mass, 72.62 +/- 7.42 kg;
      height, 179.27 +/- 6.58 cm) performed a predicted maximal squat test, 20-m
      sprints, squat jumps (SJs), and countermovement jumps (CMJs). Absolute strength
      showed the strongest correlations with 5-m sprint times (r = -0.596, p < 0.001,
      power = 0.99), SJ height (r = 0.762, p < 0.001, power = 1.00), and CMJ height (r
      = 0.760, p < 0.001, power = 1.00), whereas relative strength demonstrated the
      strongest correlation with 20-m sprint times (r = -0.672, p < 0.001, power =
      0.99). The results of this study illustrate the importance of developing high
      levels of lower-body strength to enhance sprint and jump performance in youth
      soccer players, with stronger athletes demonstrating superior sprint and jump
      performances.

PMID- 23542879
TI  - Systematic review of core muscle activity during physical fitness exercises.
AB  - A consensus has not been reached among strength and conditioning specialists
      regarding what physical fitness exercises are most effective to stimulate
      activity of the core muscles. Thus, the purpose of this article was to
      systematically review the literature on the electromyographic (EMG) activity of 3
      core muscles (lumbar multifidus, transverse abdominis, quadratus lumborum) during
      physical fitness exercises in healthy adults. CINAHL, Cochrane Central Register
      of Controlled Trials, EMBASE, PubMed, SPORTdiscus, and Web of Science databases
      were searched for relevant articles using a search strategy designed by the
      investigators. Seventeen studies enrolling 252 participants met the review's
      inclusion/exclusion criteria. Physical fitness exercises were partitioned into 5
      major types: traditional core, core stability, ball/device, free weight, and
      noncore free weight. Strength of evidence was assessed and summarized for
      comparisons among exercise types. The major findings of this review with moderate
      levels of evidence indicate that lumbar multifidus EMG activity is greater during
      free weight exercises compared with ball/device exercises and is similar during
      core stability and ball/device exercises. Transverse abdominis EMG activity is
      similar during core stability and ball/device exercises. No studies were
      uncovered for quadratus lumborum EMG activity during physical fitness exercises.
      The available evidence suggests that strength and conditioning specialists should
      focus on implementing multijoint free weight exercises, rather than core-specific
      exercises, to adequately train the core muscles in their athletes and clients.

PMID- 23542880
TI  - Use of analgesics for exercise-associated pain: prevalence and predictors of use
      in recreationally trained college-aged students.
AB  - The objectives of this study were to examine the use of the analgesics for the
      relief of exercise-associated pain (EAP) and to examine personal and/or exercise
      characteristics that might potentially predict such use in recreationally trained
      college-aged individuals. Recreationally trained college-aged students (N = 263)
      were invited to complete a self-administered 16-item questionnaire concerning
      personal exercise habits and analgesic use for EAP. The primary dependent
      variable was analgesic use for EAP, and additional items sought to characterize
      patterns and behaviors related to the use. Descriptive statistics and frequencies
      were calculated for all items, and logistic regression was used to evaluate the
      ability of 4 variables to predict analgesic use for EAP: gender, length of time
      performing regular exercise, weekly frequency of aerobic exercise, and weekly
      frequency of resistance exercise. Approximately 36% of respondents reported
      analgesic use for EAP, with data indicating acute use for what is generally acute
      pain. With predictors considered individually, gender was a significant
      predictor, with female respondents being more likely to use analgesics for EAP (p
      = 0.04). With all predictors considered concurrently, the model did not
      significantly contribute to the prediction of use in this sample. Potential for
      misuse was highlighted by a large percentage of users who described themselves as
      very unlikely to follow label directions and more likely to take a dose exceeding
      recommendations. In light of research that reports a potential detriment to
      muscular regeneration when analgesics are consumed with exercise, it is important
      to be cognizant of the use of these drugs in individuals striving to improve
      muscular fitness. Coaches and trainers should educate athletes about the
      associated risks and caution those who may unnecessarily take analgesics.

PMID- 23542882
TI  - The Role of Cumulative Trauma, Betrayal, and Appraisals in Understanding Trauma
      Symptomatology.
AB  - Poor psychological outcomes are common among trauma survivors, yet not all
      survivors experience adverse sequelae. The current study examined links between
      cumulative trauma exposure as a function of the level of betrayal (measured by
      the relational closeness of the survivor and the perpetrator), trauma appraisals,
      gender, and trauma symptoms. Participants were 273 college students who reported
      experiencing at least one traumatic event on a trauma checklist. Three cumulative
      indices were constructed to assess the number of different types of traumas
      experienced that were low (LBTs), moderate (MBTs), or high in betrayal (HBTs).
      Greater trauma exposure was related to more symptoms of depression, dissociation,
      and PTSD, with exposure to HBTs contributing the most. Women were more likely to
      experience HBTs than men, but there were no gender differences in trauma-related
      symptoms. Appraisals of trauma were predictive of trauma-related symptoms over
      and above the effects explained by cumulative trauma at each level of betrayal.
      The survivor's relationship with the perpetrator, the effect of cumulative
      trauma, and their combined impact on trauma symptomatology are discussed.

PMID- 23542881
TI  - Differential tangential expansion as a mechanism for cortical gyrification.
AB  - Gyrification, the developmental buckling of the cortex, is not a random process
      the forces that mediate expansion do so in such a way as to generate consistent
      patterns of folds across individuals and even species. Although the origin of
      these forces is unknown, some theories have suggested that they may be related to
      external cortical factors such as axonal tension. Here, we investigate an
      alternative hypothesis, namely, whether the differential tangential expansion of
      the cortex alone can account for the degree and pattern-specificity of
      gyrification. Using intrinsic curvature as a measure of differential expansion,
      we initially explored whether this parameter and the local gyrification index
      (used to quantify the degree of gyrification) varied in a regional-specific
      pattern across the cortical surface in a manner that was replicable across
      independent datasets of neurotypicals. Having confirmed this consistency, we
      further demonstrated that within each dataset, the degree of intrinsic curvature
      of the cortex was predictive of the degree of cortical folding at a global and
      regional level. We conclude that differential expansion is a plausible primary
      mechanism for gyrification, and propose that this perspective offers a compelling
      mechanistic account of the co-localization of cytoarchitecture and cortical
      folds.

PMID- 23542883
TI  - Peritoneal mast cell stabilization potential of Pothos scandens L.
AB  - OBJECTIVE: To investigate the peritoneal mast cell stabilization activity of
      Pothos scandens extracts. MATERIALS AND METHODS: Pothos scandens L. (family-
      Araceae) aerial part was successively extracted with ethanol and aqueous to
      prepare extract of the plant. The extracts of P. scandens were evaluated for
      stabilization of mast cell in rat allergic models. The extract of P. scandens
      ethanolic, 50% aqueous ethanolic and aqueous (1, 10 and 100 MUg/ml) was studied
      for peritoneal mast cell stabilization activity in rat mesenteric preparation
      induced by C 48/80. RESULT: Preliminary phytochemical analysis revealed the
      presence of carbohydrates, fixed oil, proteins, alkaloids, glycosides, flavonoids
      and phenolic compounds. The ethanolic, 50% aqueous ethanolic and aqueous extracts
      of P. scandens L. showed dose dependent increase in the number of intact cells
      when compare with C48/80 at the concentration of 10 and 100 MUg/ml. It virtues
      further work towards the isolation of phytoconstituents from this plant.
      CONCLUSION: This finding provides evidence that the P. scandens L. inhibits mast
      cell-derived immediate-type allergic reactions and mast cell degranulation. P.
      scandens has a potential as allergic anti- asthmatic agent.

PMID- 23542884
TI  - Cytotoxic effects and changes in cytokine gene expression induced by microcystin
      containing extract in fish immune cells--an in vitro and in vivo study.
AB  - Blooms of cyanobacteria producing very toxic secondary metabolites (especially
      microcystins) are potent environmental stressors, hazardous not only to aquatic
      animals but also to public health. The purpose of this study was to investigate
      the effects of an extract containing microcystins on immune cells isolated from
      the common carp (Cyprinus carpio L.). In the present study it has been found that
      the extract induced apoptosis and inhibited in vitro lymphocyte proliferation. In
      addition, the results indicated the possible role of oxidative stress in this
      cytotoxicity and apoptosis. The in vivo investigations showed that the extract
      containing microcystins had greater suppressive effects on the essential
      functions of immune cells (intracellular reactive oxygen species production and
      lymphocyte proliferation) than the pure toxin alone. Moreover, immersion of fish
      in the toxic extract caused changes in the mRNA levels of various pro- and anti
      inflammatory cytokines in carp leukocytes, while after exposure to the pure
      toxin, only IL1-beta expression was markedly up-regulated. The observed
      modulatory effects on immune cells could have important implications for the
      health of planktivorous fish, which feed more frequently on toxic cyanobacteria.

PMID- 23542885
TI  - Characterization and function of an E2-17 kDa (UBE2D) in an invertebrate Haliotis
      diversicolor supertexta.
AB  - Ubiquitin-conjugating enzymes (UBE2s or E2s) are characterized by the presence of
      a highly conserved ubiquitin-conjugating (UBC) domain, which predominantly
      determines the type of ubiquitin chains and directly controls the cellular fate
      of the substrate. In this study, an E2 homolog was identified and functionally
      characterized in abalone, which we named ab-UBE2D. The full-length cDNA consists
      of 1005 bp with an ORF encoding a protein of 147 amino acids. The deduced amino
      acid sequence shows ab-UBE2D shares conserved UBC domain with other E2 proteins
      and belongs to class I E2 enzyme family, which are further confirmed by
      phylogenetic tree analysis. Real-time PCR and western blot analyses showed that
      ab-UBE2D was ubiquitously expressed in abalone and the expression level of ab
      UBE2d was significantly induced by LPS and Poly (I:C). Immunofluorescence
      microscopy staining demonstrated that native ab-UBE2D was mainly distributed in
      the cytoplast. Ubiquitination assay showed that ab-UBE2D had ubiquitin
      conjugating activity to form the enzyme-(Ub)n conjugates. Taken together, these
      results strongly suggest that ab-UBE2D is an E2 homolog and it may be involved in
      the immune response of abalone, Haliotis diversicolor supertexta.

PMID- 23542886
TI  - Direct transfer of whole genomes from bacteria to yeast.
AB  - Transfer of genomes into yeast facilitates genome engineering for genetically
      intractable organisms, but this process has been hampered by the need for
      cumbersome isolation of intact genomes before transfer. Here we demonstrate
      direct cell-to-cell transfer of bacterial genomes as large as 1.8 megabases (Mb)
      into yeast under conditions that promote cell fusion. Moreover, we discovered
      that removal of restriction endonucleases from donor bacteria resulted in the
      enhancement of genome transfer.

PMID- 23542887
TI  - Effectiveness of intravenous iron sucrose in management of iron-deficient anemia
      of pregnancy at rural hospital set up.
AB  - OBJECTIVES: Critical evaluation of iron sucrose (Malhotra, FOGSI Focus 9-11,
      2009) in terms of efficacy, safety, and feasibility at rural setup for the
      treatment of anemia of pregnancy (Raja et al., Rawal Med J 28: 40-3, 2003) along
      with any reduction in blood transfusion rate at peripartum period of 37 weeks to
      48 h within delivery. METHODS: In a prospective cohort study conducted in
      Department of Obstetrics and Gynaecology, during the year 2008 AVBRH-Wardha, 256
      consecutive women of iron-deficient anemia (IDA) treated with intravenous iron
      sucrose were studied for feasibility, safety, and efficacy of drug. Blood
      transfusion rates were compared for the years 2007 and 2008 in cases of antenatal
      women from 37 weeks onward up to 48 h post delivery. Results were analyzed by Z
      test. RESULTS: Mean rises in Hb g% were 1.1 +/- 0.2, 2.3 +/- 0.8, and 3.0 +/- 0.4
      after 1, 2, and 3 weeks, respectively. Decline in rate of blood transfusion among
      total anemic women at peripartum period was 9.36 %. CONCLUSION: Iron sucrose
      therapy is very much relevant in rural scenario.

PMID- 23542888
TI  - Stereotaxic injection of a viral vector for conditional gene manipulation in the
      mouse spinal cord.
AB  - Intraparenchymal injection of a viral vector enables conditional gene
      manipulation in distinct populations of neurons or particular regions of the
      central nervous system. We demonstrate a stereotaxic injection technique that
      allows targeted gene expression or silencing in the dorsal horn of the mouse
      spinal cord. The surgical procedure is brief. It requires laminectomy of a single
      vertebra, providing for quick recovery of the animal and unimpaired motility of
      the spine. Controlled injection of a small vector suspension volume at low speed
      and use of a microsyringe with beveled glass cannula minimize the tissue lesion.
      The local immune response to the vector depends on the intrinsic properties of
      the virus employed; in our experience, it is minor and short-lived when a
      recombinant adeno-associated virus is used. A reporter gene such as enhanced
      green fluorescent protein facilitates monitoring spatial distribution of the
      vector, and the efficacy and cellular specificity of the transfection.

PMID- 23542890
TI  - Copper(II) complexes with derivatives of pyrazole as potential antioxidant enzyme
      mimics.
AB  - A series of six mononuclear Cu(II) complexes with pyrazole-based ligands: 5-(2
      hydroxybenzoyl)-3-methyl-1-(2-pyridinyl)-1H-pyrazol-4-phosphonic acid dimethyl
      ester (1a), 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic
      acid methyl ester (1b) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1H
      pyrazole-4-carboxylic acid methyl ester (1c) were characterized regarding to
      electrochemical and antioxidant properties. All complexes exhibit suitable
      Cu(II)/Cu(I) redox potential (E1/2) to act as antioxidant enzymes mimic. The five
      of these complexes were found to be trifunctional enzyme mimics possessing SOD,
      CAT and GPx-like catalytic activities. Moreover, Cu(II) complexes were capable to
      decrease ROS level in melanoma cells and observed effects were not merely a
      reflection of cytotoxicity.

PMID- 23542891
TI  - Enhanced diastolic filling performance with lifelong physical activity in aging
      mice.
AB  - PURPOSE: The purpose of this study was to investigate the age-related changes in
      diastolic filling parameters in the aging hearts of active C57Bl/6J mice
      throughout the life span to indicate optimal age periods for improvements in
      resting diastolic parameters. METHODS: Fourteen C57Bl/6J mice (seven males and
      seven females) were individually housed at 8 wk of age in cages with a running
      wheel, magnetic sensor, and digital odometer. Duration, distance, and running
      velocity were recorded daily. Fourteen additional mice C57Bl/6J mice (seven males
      and seven females) were placed in individual cages without running wheels at 8 wk
      of age. Pulsed-wave Doppler transmitral inflow recordings with a SONOS 5500
      ultrasound and 15-6L ultrasound probe were used to image the left ventricle every
      4 wk throughout the life span. RESULTS: Peak E wave filling velocities were
      significantly greater by the start of the second quarter of the life span in the
      mice with access to running wheels (P < 0.0001). Peak E wave velocities improved
      in both groups during the first half of the life span (P < 0.0001) and declined
      throughout the second half of the life span (P < 0.0001). Early-to-late (E:A)
      filling ratio was significantly greater for the physically active mice by the
      start of the second quarter of the life span (P < 0.0001) and continued
      throughout most of the remainder of the life span (P < 0.0001). No differences
      were observed between the two groups of mice with peak A wave filling velocities
      (P > 0.05). Similar findings were observed when corrected for resting heart rate.
      CONCLUSIONS: Lifelong physical activity resulted in greater diastolic filling
      parameters by the second quarter of the life span, highlighting the clinical
      importance of regular aerobic activity in young adulthood as a mechanism for
      improved left ventricular performance with aging.

PMID- 23542892
TI  - Physical education can improve insulin resistance: the LOOK randomized cluster
      trial.
AB  - PURPOSE: As impaired glucose metabolism may arise progressively during childhood,
      we sought to determine whether the introduction of specialist-taught school
      physical education (PE) based on sound educational principles could improve
      insulin resistance (IR) in elementary school children. METHODS: In this 4-yr
      cluster-randomized intervention study, participants were 367 boys and 341 girls
      (mean age = 8.1 yr, SD = 0.35) initially in grade 2 in 29 elementary schools
      situated in suburbs of similar socioeconomic status. In 13 schools, 100 min.wk-1
      of PE, usually conducted by general classroom teachers, was replaced with two
      classes per week taught by visiting specialist PE teachers; the remaining schools
      formed the control group. Teacher and pupil behavior were recorded, and
      measurements in grades 2, 4, and 6 included fasting blood glucose and insulin to
      calculate the homeostatic model of IR, percent body fat, physical activity,
      fitness, and pubertal development. RESULTS: On average, the intervention PE
      classes included more fitness work than the control PE classes (7 vs 1 min, P <
      0.001) and more moderate physical activity (17 vs 10 min, P < 0.001). With no
      differences at baseline, by grade 6, the intervention had lowered IR by 14% (95%
      confidence interval = 1%-31%) in the boys and by 9% (95% confidence interval = 5%
      26%) in the girls, and the percentage of children with IR greater than 3, a
      cutoff point for metabolic risk, was lower in the intervention than the control
      group (combined, 22% vs 31%, P = 0.03; boys, 12% vs 21%, P = 0.06; girls, 32% vs
      40%, P = 0.05). CONCLUSIONS: Specialist-taught primary school PE improved IR in
      community-based children, thereby offering a primordial preventative strategy
      that could be coordinated widely although a school-based approach.

PMID- 23542893
TI  - Quiet eye and choking: online control breaks down at the point of performance
      failure.
AB  - PURPOSE: The quiet eye (QE) is a characteristic of highly skilled perceptual and
      motor performance that has been shown to be sensitive to increases in anxiety.
      The present study is the first to examine changes in the QE at the precise point
      of performance failure under heightened anxiety. QE durations were compared for
      the first, penultimate, and final (missed) putts taken in a pressurized shootout
      task. To probe the effects of anxiety more specifically, differences in the
      component of the QE that occurred before (QE-pre), during (QE-online), and after
      (QE-dwell) putter movement were examined. METHODS: Fifty expert golfers (average
      handicap of 3.6) performed putts under pressure until they missed ("shootout").
      Gaze was recorded throughout with an ASL Mobile Eye Tracker. Total QE,
      preprogramming QE (the proportion of QE that occurred before backswing; QE-pre),
      online control QE (the proportion of QE that occurred during the putting stroke;
      QE-online), and QE-dwell (the proportion of QE that occurred after putter-ball
      contact; QE-dwell) were calculated for the first, penultimate, and final putts.
      RESULTS: Total QE duration was significantly shorter for the final (missed) putt
      compared with the first and penultimate (successful) putts. Although QE-pre
      duration was similar across the three putts, the components of the QE occurring
      during (QE-online) and after (QE-dwell) putter movement were significantly
      shorter on the missed putt. CONCLUSIONS: Performance failure under pressure
      appears to be due to disruptions in attentional control once movement has been
      initiated. These findings support the predictions of attentional control theory
      and suggest that the QE may have an online control function, providing visual
      sensory information as the movement unfolds.

PMID- 23542894
TI  - Older adults with type 2 diabetes store more heat during exercise.
AB  - INTRODUCTION: It is unknown if diabetes-related reductions in local skin blood
      flow (SkBF) and sweating (LSR) measured during passive heat stress translate into
      greater heat storage during exercise in the heat in individuals with type 2
      diabetes (T2D) compared with nondiabetic control (CON) subjects. PURPOSE: This
      study aimed to examine the effects of T2D on whole-body heat exchange during
      exercise in the heat. METHODS: Ten adults (6 males and 4 females) with T2D and 10
      adults (6 males and 4 females) without diabetes matched for age, sex, body
      surface area, and body surface area and aerobic fitness cycled continuously for
      60 min at a fixed rate of metabolic heat production (~370 W) in a whole-body
      direct calorimeter (30 degrees C and 20% relative humidity). Upper back LSR,
      forearm SkBF, rectal temperature, and heart rate were measured continuously.
      Whole-body heat loss and changes in body heat content (DeltaHb) were determined
      using simultaneous direct whole-body and indirect calorimetry. RESULTS: Whole
      body heat loss was significantly attenuated from 15 min throughout the remaining
      exercise with the differences becoming more pronounced over time for T2D relative
      to CON (P = 0.004). This resulted in a significantly greater DeltaHb in T2D (367
      +/- 35; CON, 238 +/- 25 kJ, P = 0.002). No differences were measured during
      recovery (T2D, -79 +/- 23; CON, -132 +/- 23 kJ, P = 0.083). By the end of the 60
      min recovery, the T2D group lost only 21% (79 kJ) of the total heat gained during
      exercise, whereas their nondiabetic counterparts lost in excess of 55% (131 kJ).
      No difference were observed in LSR, SkBF, rectal temperature or heart rate during
      exercise. Similarly, no differences were measured during recovery with the
      exception that heart rate was elevated in the T2D group relative to CON
      (p=0.004). CONCLUSION: Older adults with T2D have a reduced capacity to dissipate
      heat during exercise, resulting in a greater heat storage and therefore level of
      thermal strain.

PMID- 23542895
TI  - Does vigorous physical activity provide additional benefits beyond those of
      moderate?
AB  - BACKGROUND: Although guidelines suggest that vigorous physical activity (PA)
      confers "extra" benefits compared with those from moderate-intensity activity
      alone, the magnitude of this additional benefit is unclear. The aim was to
      compare the reduction in risk of hypertension (HT) and depressive symptoms (DS)
      for 12 yr in middle-age women who reported (a) only moderate-intensity PA (MOPA)
      and (b) a combination of moderate and vigorous PA (MVPA), after controlling for
      overall volume of activity. METHODS: The study involved 11,285 participants in
      the Australian Longitudinal Study on Women's Health, who completed surveys in
      1998 (age = 46-52 yr), 2001, 2004, 2007, and 2010. Generalized estimating
      equation models (with 3-yr time lag) were used to examine the relationship
      between PA in seven categories from 0 to >2000 MET.min.wk-1 and occurrence of HT
      and DS for women who reported MOPA or MVPA. RESULTS: For HT, risk was slightly
      lower for MVPA than for MOPA across the entire range of PA levels, but this
      difference was only significant at the highest PA level (>2000; odds ratio [OR] =
      0.80 MOPA and 0.56 MVPA). For DS, OR values were similar in both groups up to 500
      MET.min.wk-1, then slightly lower for MVPA than for MOPA at higher PA levels.
      Again, this difference was only significant at the highest PA level (>2000; OR =
      0.57 MOPA and 0.42 MVPA). OR values were slightly attenuated in adjusted models.
      CONCLUSIONS: Doing both vigorous and moderate activity does not have significant
      additional benefits in terms of HT and DS, above those from moderate-intensity
      activity alone, except at very high levels of PA.

PMID- 23542896
TI  - Changes in gene expression in the frontal cortex of rats with pilocarpine-induced
      status epilepticus after sleep deprivation.
AB  - Sleep and epilepsy present a bidirectional interaction. Sleep complaints are
      common in epilepsy, and sleep deprivation may provoke seizures. However, the
      mechanisms underlying this relationship are unknown. Thus, this study
      investigated the effects of paradoxical sleep deprivation (PSD24h) and total
      sleep deprivation (TSD6h) in the expression of genes related to reactive oxygen
      species and nitric oxide production in the frontal cortex of a rodent model of
      temporal lobe epilepsy (PILO). The data show that PILO rats had increased NOX-2
      expression and decreased SOD expression, independent of sleep. Higher NOX-2
      expression was observed only in PILO rats subjected to the control condition and
      TSD6h. Also, eNOS and DDAH1 were increased in the PILO group submitted to TSD6h.
      Moreover, CAT expression in the frontal cortex of PILO rats submitted to PSD24h
      was reduced compared to that of PILO rats that were not sleep-deprived. The
      molecular changes found in the frontal cortex of PILO rats following sleep
      deprivation suggest a mechanism via oxidative stress.

PMID- 23542898
TI  - Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma
      triglycerides in rodents, nonhuman primates, and humans.
AB  - RATIONALE: Elevated plasma triglyceride levels have been recognized as a risk
      factor for the development of coronary heart disease. Apolipoprotein C-III (apoC
      III) represents both an independent risk factor and a key regulatory factor of
      plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have
      been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no
      selective apoC-III therapeutic agent has been evaluated in the clinic. OBJECTIVE:
      To test the hypothesis that selective inhibition of apoC-III with antisense drugs
      in preclinical models and in healthy volunteers would reduce plasma apoC-III and
      triglyceride levels. METHODS AND RESULTS: Rodent- and human-specific second
      generation antisense oligonucleotides were identified and evaluated in
      preclinical models, including rats, mice, human apoC-III transgenic mice, and
      nonhuman primates. We demonstrated the selective reduction of both apoC-III and
      triglyceride in all preclinical pharmacological evaluations. We also showed that
      inhibition of apoC-III was well tolerated and not associated with increased liver
      triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled,
      phase I clinical study was performed in healthy subjects. Administration of the
      human apoC-III antisense drug resulted in dose-dependent reductions in plasma
      apoC-III, concomitant lowering of triglyceride levels, and produced no clinically
      meaningful signals in the safety evaluations. CONCLUSIONS: Antisense inhibition
      of apoC-III in preclinical models and in a phase I clinical trial with healthy
      subjects produced potent, selective reductions in plasma apoC-III and
      triglyceride, 2 known risk factors for cardiovascular disease. This compelling
      pharmacological profile supports further clinical investigations in
      hypertriglyceridemic subjects.

PMID- 23542897
TI  - Beta cell dysfunction and insulin resistance.
AB  - Beta cell dysfunction and insulin resistance are inherently complex with their
      interrelation for triggering the pathogenesis of diabetes also somewhat
      undefined. Both pathogenic states induce hyperglycemia and therefore increase
      insulin demand. Beta cell dysfunction results from inadequate glucose sensing to
      stimulate insulin secretion therefore elevated glucose concentrations prevail.
      Persistently elevated glucose concentrations above the physiological range result
      in the manifestation of hyperglycemia. With systemic insulin resistance, insulin
      signaling within glucose recipient tissues is defective therefore hyperglycemia
      perseveres. Beta cell dysfunction supersedes insulin resistance in inducing
      diabetes. Both pathological states influence each other and presumably
      synergistically exacerbate diabetes. Preserving beta cell function and insulin
      signaling in beta cells and insulin signaling in the glucose recipient tissues
      will maintain glucose homeostasis.

PMID- 23542899
TI  - Detection of DNA hybridization by field-effect DNA-based biosensors: mechanisms
      of signal generation and open questions.
AB  - We model theoretically the electrostatic effects taking place upon DNA
      hybridization in dense DNA arrays immobilized on a layer of Au nano-particles
      deposited on the surface of a field-effect-based DNA capacitive biosensor. We
      consider the influence of separation of a charged analyte from the sensor surface
      and the salinity of electrolyte solution, in the framework of both linear and
      nonlinear Poisson-Boltzmann theories. The latter predicts a substantially weaker
      sensor signals due to electrostatic saturation effects that is the main
      conclusion of this paper. We analyze how different physical parameters of dense
      DNA brushes affect the magnitude of hybridization signals. The list includes the
      fraction of DNA charge neutralization, the length and spatial conformations of
      adsorbed DNA molecules, as well as the discreteness of DNA charges. We also
      examine the effect of Donnan ionic equilibrium in DNA lattices on the sensor
      response. The validity of theoretical models is contrasted against recent
      experimental observations on detection of DNA hybridization via its intrinsic
      electric charge. The sensitivity of such biochemical sensing devices, their
      detection limit, and DNA hybridization efficiency are briefly discussed in the
      end.

PMID- 23542900
TI  - Study on the electrochemical catalytic properties of the topological insulator
      Bi2Se3.
AB  - In this work, the electrochemical catalytic properties of the topological
      insulator bismuth selenide (Bi2Se3) were first studied. In the presence of Bi2Se3
      the reduction current of dissolved O2 could be significantly enhanced. The
      electron transfer resistivity (Rct) was greatly reduced at the Bi2Se3-PVP
      modified electrode as evidenced by the electrochemical impedance spectrometry,
      implying that the topological insulator Bi2Se3 could facilitate the electron
      transfer at the interface due to the excellent surface conductivity. Based on the
      high electrochemical catalytic activity for the reduction of dissolved O2, the
      Bi2Se3-PVP modified electrode was used to detect glucose with the modification of
      glucose oxidase, and applied for the detection of glucose in human blood serum.

PMID- 23542901
TI  - An Engraftable Human Embryonic Stem Cell Neuronal Lineage-Specific Derivative
      Retains Embryonic Chromatin Plasticity for Scale-Up CNS Regeneration.
AB  - BACKGROUND: Pluripotent human embryonic stem cells (hESCs) proffer cures for a
      wide range of neurological disorders by supplying the diversity of human neuronal
      cell types in the developing CNS for repair. However, realizing the therapeutic
      potential of hESC derivatives has been hindered by generating neuronal cells from
      pluripotent cells through uncontrollable and inefficient multi-lineage
      differentiation. Previously, we used a defined platform to identify retinoic acid
      as sufficient to induce the specification of neuroectoderm direct from the
      pluripotent state of hESCs and trigger uniform neuronal lineage-specific
      progression to human neuronal progenitors (hESC-I hNuPs) and neurons (hESC-I
      hNus) in the developing CNS with high efficiency. METHODS: Having achieved
      uniformly conversion of pluripotent hESCs to a neuronal lineage, in this study,
      the expression and intracellular distribution patterns of a set of chromatin
      modifiers in hESC-I hNuPs were examined and compared to the two prototypical
      neuroepithelial-like human neural stem cells (hNSCs) either derived from hESCs or
      isolated directly from the human fetal neuroectoderm in vivo. RESULTS: These hESC
      I hNuPs expressed high levels of active chromatin modifiers, including acetylated
      histone H3 and H4, HDAC1, Brg-1, and hSNF2H, retaining an embryonic acetylated
      globally active chromatin state. Consistent with this observation, several
      repressive chromatin remodeling factors regulating histone H3K9 methylation,
      including SIRT1, SUV39H1, and Brm, were inactive in hESC-I hNuPs. These Nurr1
      positive hESC-I hNuPs, which did not express the canonical hNSC markers, yielded
      neurons efficiently and exclusively, as they did not differentiate into glial
      cells. Following engraftment in the brain, hESC-I hNuPs yielded well-dispersed
      and well-integrated human neurons at a high prevalence. CONCLUSIONS: These
      observations suggest that, unlike the prototypical neuroepithelial-like nestin
      positive hNSCs, these in vitro neuroectoderm-derived Nurr1-positive hESC-I hNuPs
      are a more neuronal lineage-specific and plastic human stem cell derivative,
      providing an engraftable human embryonic neuronal progenitor in high purity and
      large supply with adequate neurogenic potential for scale-up CNS regeneration as
      stem cell therapy to be translated to patients in clinical trials.

PMID- 23542902
TI  - Activation of different split functionalities on re-association of RNA-DNA
      hybrids.
AB  - Split-protein systems, an approach that relies on fragmentation of proteins with
      their further conditional re-association to form functional complexes, are
      increasingly used for various biomedical applications. This approach offers tight
      control of protein functions and improved detection sensitivity. Here we report a
      similar technique based on a pair of RNA-DNA hybrids that can be used generally
      for triggering different split functionalities. Individually, each hybrid is
      inactive but when two cognate hybrids re-associate, different functionalities are
      triggered inside mammalian cells. As a proof of concept, this work mainly focuses
      on the activation of RNA interference. However, the release of other
      functionalities (such as resonance energy transfer and RNA aptamer) is also
      shown. Furthermore, in vivo studies demonstrate a significant uptake of the
      hybrids by tumours together with specific gene silencing. This split
      functionality approach presents a new route in the development of 'smart' nucleic
      acid-based nanoparticles and switches for various biomedical applications.

PMID- 23542903
TI  - Terahertz spin current pulses controlled by magnetic heterostructures.
AB  - In spin-based electronics, information is encoded by the spin state of electron
      bunches. Processing this information requires the controlled transport of spin
      angular momentum through a solid, preferably at frequencies reaching the so far
      unexplored terahertz regime. Here, we demonstrate, by experiment and theory, that
      the temporal shape of femtosecond spin current bursts can be manipulated by using
      specifically designed magnetic heterostructures. A laser pulse is used to drive
      spins from a ferromagnetic iron thin film into a non-magnetic cap layer that has
      either low (ruthenium) or high (gold) electron mobility. The resulting transient
      spin current is detected by means of an ultrafast, contactless amperemeter based
      on the inverse spin Hall effect, which converts the spin flow into a terahertz
      electromagnetic pulse. We find that the ruthenium cap layer yields a considerably
      longer spin current pulse because electrons are injected into ruthenium d states,
      which have a much lower mobility than gold sp states. Thus, spin current pulses
      and the resulting terahertz transients can be shaped by tailoring magnetic
      heterostructures, which opens the door to engineering high-speed spintronic
      devices and, potentially, broadband terahertz emitters.

PMID- 23542904
TI  - Nanowire liquid pumps.
AB  - The ability to form tiny droplets of liquids and control their movements is
      important in printing or patterning, chemical reactions and biological assays. So
      far, such nanofluidic capabilities have principally used components such as
      channels, nozzles or tubes, where a solid encloses the transported liquid. Here,
      we show that liquids can flow along the outer surface of solid nanowires at a
      scale of attolitres per second and the process can be directly imaged with in
      situ transmission electron microscopy. Microscopy videos show that an ionic
      liquid can be pumped along tin dioxide, silicon or zinc oxide nanowires as a thin
      precursor film or as beads riding on the precursor film. Theoretical analysis
      suggests there is a critical film thickness of ~10 nm below which the liquid
      flows as a flat film and above which it flows as discrete beads. This critical
      thickness is the result of intermolecular forces between solid and liquid, which
      compete with liquid surface energy and Rayleigh-Plateau instability.

PMID- 23542905
TI  - Spatial discrimination and visual discrimination: two methods evaluating learning
      and memory in juvenile Gottingen minipigs.
AB  - Two methods investigating learning and memory in juvenile Gottingen minipigs were
      evaluated for potential use in preclinical toxicity testing. Twelve minipigs were
      tested using a spatial hole-board discrimination test including a learning phase
      and two memory phases. Five minipigs were tested in a visual discrimination test.
      The juvenile minipigs were able to learn the spatial hole-board discrimination
      test and showed improved working and reference memory during the learning phase.
      Performance in the memory phases was affected by the retention intervals, but the
      minipigs were able to remember the concept of the test in both memory phases.
      Working memory and reference memory were significantly improved in the last
      trials of the memory phases. In the visual discrimination test, the minipigs
      learned to discriminate between the three figures presented to them within 9-14
      sessions. For the memory test, all minipigs performed 9/12 correct choices or
      better. Juvenile Gottingen minipigs are able to learn to perform in a spatial
      hole-board discrimination test as well as in a visual discrimination test,
      showing an increase in performance over time. Both tests have considerable scope
      to assess learning and memory of pigs, and we seem to have succeeded in
      establishing two test systems suitable for performing preclinical toxicity
      testing in juvenile minipigs.

PMID- 23542906
TI  - Capillary-free vascularized retina in patients with aggressive posterior
      retinopathy of prematurity and late retinal capillary formation.
AB  - PURPOSE: To report the clinical features, clinical course, and treatment outcomes
      after laser photocoagulation in infants with aggressive posterior retinopathy of
      prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six
      patients (12 eyes) with APROP and capillary-free zones in vascularized retina
      were retrospectively reviewed. Twelve eyes of six infants were included and were
      treated with laser photocoagulation for avascular retina and for capillary-free
      zones in vascularized retina, except for the posterior pole, and fundus findings
      were photographically-documented in sequence. In addition, anatomic and visual
      outcomes were evaluated with complications of APROP. RESULTS: Among all of the
      consecutive infants with APROP, capillary-free zones in vascularized retina were
      demonstrated in 24% of the infants. All of the infants were >27 weeks of
      gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes
      (58.3%) had favorable outcomes, and late capillary filling in capillary-free
      zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to
      retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting
      posterior pole. The visual outcomes were associated with anatomic outcomes.
      CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free
      zones were comparable to previously reported infants with APROP. The late
      capillary filling of capillary-free zones in vascularized retina was noted, and
      angiogenesis was considered to be involved. This process toward normal capillary
      formation or neovascularization in APROP, might determine its outcome.

PMID- 23542907
TI  - Bioreactor design for perfusion-based, highly-vascularized organ regeneration.
AB  - Bioartificial or laboratory-grown organs is a growing field centered on
      developing replacement organs and tissues to restore body function and providing
      a potential solution to the shortage of donor organs for transplantation. With
      the entry of engineered planar tissues, such as bladder and trachea, into
      clinical studies, an increasing focus is being given to designing complex, three
      dimensional solid organs. As tissues become larger, thicker and more complex, the
      vascular network becomes crucial for supplying nutrients and maintaining
      viability and growth of the neo-organ. Perfusion decellularization, the process
      of removing cells from an entire organ, leaves the matrix of the vascular network
      intact. Organ engineering requires a delicate process of decellularization,
      sterilization, reseeding with appropriate cells, and organ maturation and
      stimulation to ensure optimal development. The design of bioreactors to
      facilitate this sequence of events has been refined to the extent that some
      bioartificial organs grown in these systems have been transplanted into recipient
      animals with sustained, though limited, function. This review focuses on the
      state-of-art in bioreactor development for perfusion-based bioartificial organs
      and highlights specific design components in need of further refinement.

PMID- 23542908
TI  - Incentive motivational salience and the human brain.
AB  - In this paper the concept of incentive motivational salience is briefly
      described, pioneering studies on the subject of the mesolimbic motivational
      system are reviewed, and studies we have been involved in conducting which
      elaborate on this subject are discussed. In particular, we aim to show that the
      mesolimbic motivational system is recruited as a reaction to primary and
      secondary reinforcers as a function of salience, that is independent of valence.
      Furthermore, studies showing that both psychological and pharmacological
      interventions can affect the function of the mesolimbic motivational system and
      how its' dysfunction is related to psychopathological phenomena with an emphasis
      on psychosis are discussed. 

PMID- 23542909
TI  - Cognitive enhancers for the treatment of anxiety disorders.
AB  - Traditional treatments for anxiety disorders include cognitive-behavioral therapy
      and anxiolytic medications. Although these treatments are more effective than
      placebo, there is still considerable room for further improvement. Unfortunately,
      combining these different modalities is generally not substantially better than
      monotherapies. Recently, researchers have turned their attention toward
      translating preclinical research on the neural circuitry underlying fear
      extinction to clinical applications for the treatment of anxiety disorders with
      the goal to augment the learning process during exposure-based procedures with
      cognitive enhancers. This review examines d-cycloserine, cortisol,
      catecholamines, yohimbine, oxytocin, modafinil, as well as nutrients and
      botanicals as agents to augment treatment for anxiety disorders. D-cycloserine
      shows the most empirical support. Other promising agents include cortisol,
      catecholamines, yohimbine, and possibly oxytocin. Less support comes from studies
      that examined nutrients and botanicals, such as caffeine, nicotine, and omega-3
      fatty acid. Limitations of the exiting literature and future research directions
      are discussed. 

PMID- 23542911
TI  - Evaluation of a new visual uptake scoring scale for 18F-fluorothymidine positron
      emission tomography in the diagnosis of pulmonary lesions.
AB  - PURPOSE: The aim of this analysis was to evaluate a new visual scoring scale
      developed to facilitate the qualitative appraisal of lesion uptake on (18)F
      fluorothymidine PET ((18)F-FLT-PET). METHODS: Sixty-two patients with a pulmonary
      lesion of unknown aetiology who had undergone an F-fluorodeoxyglucose
      PET/computed tomography (CT) suspicious for malignancy prospectively underwent an
      (18)F-FLT-PET/CT. Three nuclear medicine physicians independently reviewed each
      (18)F-FLT-PET/CT scan with knowledge of the location of the pulmonary lesion but
      blinded to the final diagnosis. They scored the lesion (18)F-FLT uptake as
      follows: (0) no visible uptake; (1) <spleen; (2) >= spleen, but <both liver and
      marrow; (3) between liver and marrow; (4) >liver and >marrow. Lesion mean
      (SUV(mean)) and maximum (SUV(max)) standardized uptake values were measured in a
      separate session. RESULTS: In all, 35 lesions were malignant and 27 were benign,
      as assessed on the basis of surgery, biopsy or follow-up of at least 12 months.
      Visual score, SUV(mean) and SUV(max) were statistically different between benign
      and malignant lesions. The visual scoring scale showed substantial to almost
      perfect interobserver agreement with a weighted kappa value of 0.84, 0.67 and
      0.65 for each observer pair. The visual score was highly correlated to SUV(mean)
      and SUV(max) (r=0.83 and 0.87, respectively) and described a logarithmic pattern
      in relation to SUV(mean) and SUV(max) (r =0.67 and 0.72, respectively). The area
      under the receiver-operating characteristic curve for the visual score was 0.86
      and was statistically different from that for SUV(mean) (0.77; P=0.026) and
      SUV(max) (0.79; P=0.047). CONCLUSION: The (18)F-FLT scoring scale we propose is
      easy to use with high interobserver agreement and a significantly better
      discriminative capacity compared with SUV measurements. It has the potential to
      harmonize the qualitative interpretation of (18)F-FLT-PET/CT in lung cancer
      diagnosis.

PMID- 23542910
TI  - Psychopathy: developmental perspectives and their implications for treatment.
AB  - Psychopathy is a mental disorder marked by deficient emotional responses, lack of
      empathy, and poor behavioral controls, commonly resulting in persistent
      antisocial deviance and criminal behavior. Accumulating research suggests that
      psychopathy follows a developmental trajectory with strong genetic influences,
      and which precipitates deleterious effects on widespread functional networks,
      particularly within paralimbic regions of the brain. While traditional
      therapeutic interventions commonly administered in prisons and forensic
      institutions have been notoriously ineffective at combating these outcomes,
      alternative strategies informed by an understanding of these specific
      neuropsychological obstacles to healthy development, and which target younger
      individuals with nascent symptoms of psychopathy are more promising. Here we
      review recent neurobehavioral and neuroimaging literature that informs our
      understanding of the brain systems compromised in psychopathy, and apply these
      data to a broader understanding of its developmental course, ultimately promoting
      more proactive intervention strategies profiting from adaptive neuroplasticity in
      youth. 

PMID- 23542912
TI  - Comparison of SPECT-CT results and intraoperative detection of sentinel lymph
      nodes in endometrial cancer.
AB  - OBJECTIVES: The aim of the study was to compare the results of single-photon
      emission computed tomography-computed tomography (SPECT-CT) with those of
      intraoperative gamma probe detection and assess the clinical utility of SPECT-CT
      for sentinel lymph node biopsy in endometrial cancer. MATERIALS AND METHODS: We
      investigated 70 patients with endometrial cancer who underwent total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy
      (routine pelvic and para-aortic lymphadenectomy was additionally performed in
      high-risk patients). Tc-99m radiocolloid albumin was injected into the cervix and
      a blue dye was injected superficially into the fundus. RESULTS: SPECT-CT revealed
      hot spots in 64 patients (91.4%). The detection rates were 97.1 and 94.3% using
      the combined technique and the hand-held gamma probe, respectively. In 19 cases
      (27.1%) 35 hot spots detected on SPECT-CT were not diagnosed as sentinel lymph
      nodes (SLNs) during surgery. In each patient with undetected hot spots located in
      the common iliac or para-aortic regions, hot SLNs were found during surgery in
      the obturator or external iliac region. In addition, SPECT-CT had detected 88.9%
      of the SLNs found during surgery. With respect to the 13 cases not detected on
      SPECT-CT, the hot SLNs had very low activity. Using the combined method, 95.1% of
      SLNs were found in typical locations (external iliac or obturator nodes). There
      were two metastatic nodes: one in SLN and one in nonsentinel node. CONCLUSION:
      SPECT-CT yields a high SLN detection rate; however, there is significant
      discrepancy in comparison with intraoperative findings, which limits its clinical
      utility. In addition, in the majority of cases SLNs are found in typical areas,
      which means that they can be reliably detected using an intraoperative gamma
      probe.

PMID- 23542913
TI  - Value of baseline and follow-up whole-body bone scans in detecting bone
      metastasis in high-risk breast cancer patients.
AB  - OBJECTIVE: The aim of the study was to test the value of routine baseline and
      follow-up bone scans in societies with a prevalence of high-risk breast cancer
      features. PATIENTS AND METHODS: The medical records of 261 Jordanian breast
      cancer patients were reviewed. Patients who had (a) breast cancer proven by
      pathology, (b) had undergone a baseline bone scan, and (c) had undergone follow
      up bone scan(s) for at least 12 months were included in the study. The patients
      were divided into three groups. Group 1 included 171 patients who had negative
      bone scans; group 2 included 52 patients who had negative baseline bone scans but
      developed bone metastasis on follow-up; and group 3 included 38 patients who had
      bone metastasis at presentation. RESULTS: Patients' ages ranged between 21 and 85
      years with mean +/- SD of 49.7 (+/- 11.3) years. About 55% of our patients were
      younger than 50 years. Clinicopathological stages were as follows: 14% of
      patients were in stage I, 42% were in stage II, 30% were in stage III, and 14%
      were in stage IV. A significant proportion of our patients have high-risk
      features. Fourteen percent of the patients already had bone metastasis at
      diagnosis and 20% developed bone metastasis on follow-up. Sixty percent of group
      2 patients developed bone metastasis within 2 years after diagnosis and the rest
      (40%) developed bone metastasis 2 years after diagnosis (<= 13 years).
      CONCLUSION: Within the limitations of this retrospective study, in a country like
      Jordan with greater prevalence of high-risk breast cancer features, a routine
      baseline whole-body bone scan might be justifiable. Follow-up whole-body bone
      scans might result in better quality of life and lower skeletal-related
      morbidity. Further prospective work is suggested.

PMID- 23542914
TI  - The complex interaction between anxiety and cognition: insight from spatial and
      verbal working memory.
AB  - Anxiety can be distracting, disruptive, and incapacitating. Despite problems with
      empirical replication of this phenomenon, one fruitful avenue of study has
      emerged from working memory (WM) experiments where a translational method of
      anxiety induction (risk of shock) has been shown to disrupt spatial and verbal WM
      performance. Performance declines when resources (e.g., spatial attention,
      executive function) devoted to goal-directed behaviors are consumed by anxiety.
      Importantly, it has been shown that anxiety-related impairments in verbal WM
      depend on task difficulty, suggesting that cognitive load may be an important
      consideration in the interaction between anxiety and cognition. Here we use both
      spatial and verbal WM paradigms to probe the effect of cognitive load on anxiety
      induced WM impairment across task modality. Subjects performed a series of
      spatial and verbal n-back tasks of increasing difficulty (1, 2, and 3-back) while
      they were safe or at risk for shock. Startle reflex was used to probe anxiety.
      Results demonstrate that induced-anxiety differentially impacts verbal and
      spatial WM, such that low and medium-load verbal WM is more susceptible to
      anxiety-related disruption relative to high-load, and spatial WM is disrupted
      regardless of task difficulty. Anxiety impacts both verbal and spatial processes,
      as described by correlations between anxiety and performance impairment, albeit
      the effect on spatial WM is consistent across load. Demanding WM tasks may exert
      top-down control over higher-order cortical resources engaged by anxious
      apprehension, however high-load spatial WM may continue to experience additional
      competition from anxiety-related changes in spatial attention, resulting in
      impaired performance. By describing this disruption across task modalities, these
      findings inform current theories of emotion-cognition interactions and may
      facilitate development of clinical interventions that seek to target cognitive
      impairments associated with anxiety.

PMID- 23542915
TI  - The role of surgery for metastatic renal cell carcinoma in the era of targeted
      therapies.
AB  - PURPOSE: With the emergence of targeted therapies, the indications of
      cytoreductive nephrectomy have to be redefined. This review article presents the
      evidence data guiding our current indications of surgery in the management of
      metastatic renal cell carcinoma (mRCC) in the era of targeted therapies. METHODS:
      A nonsystematic review of the electronic databases PubMed and MEDLINE from 1980
      to 2012 was performed and limited to English language. RESULTS: Two studies based
      on immunotherapy (EORTC 30947 and SWOG 8949) were at the origins of the
      recommendations on initial nephrectomy for patients with mRCC. Since the
      introduction of angiogenesis inhibitors, there is still no high-level evidence
      from prospective studies assessing the indication of surgery for mRCC. However,
      surgery still has its importance in the management of primary tumors and
      metastasis with the objective of an optimal balance between morbidity, quality of
      life, and survival. The treatment sequence between surgery and targeted therapies
      is still to be established and two randomized prospective studies were then
      specifically designed and are currently recruiting. CONCLUSIONS: Preliminary
      evidence data from retrospective series seem to be in favor of a benefit of
      surgery for patients with good and intermediate prognosis. However, patients'
      inclusions in current prospective studies are highly recommended to clearly
      precise nephrectomy's indications.

PMID- 23542917
TI  - Cardiac function and lipid distribution in rats fed a high-fat diet: in vivo
      magnetic resonance imaging and spectroscopy.
AB  - Obesity is a major risk factor in the development of cardiovascular disease, type
      2 diabetes, and its pathophysiological precondition insulin resistance. Very
      little is known about the metabolic changes that occur in the myocardium and
      consequent changes in cardiac function that are associated with high-fat
      accumulation. Therefore, cardiac function and metabolism were evaluated in
      control rats and those fed a high-fat diet, using magnetic resonance imaging,
      magnetic resonance spectroscopy, mRNA analysis, histology, and plasma
      biochemistry. Analysis of blood plasma from rats fed the high-fat diet showed
      that they were insulin resistant (P < 0.001). Our high-fat diet model had higher
      heart weight (P = 0.005) and also increasing trend in septal wall thickness (P =
      0.07) compared with control diet rats. Our results from biochemistry, magnetic
      resonance imaging, and mRNA analysis confirmed that rats on the high-fat diet had
      moderate diabetes along with mild cardiac hypertrophy. The magnetic resonance
      spectroscopy results showed the extramyocellular lipid signal only in the spectra
      from high-fat diet rats, which was absent in the control diet rats. The
      intramyocellular lipids in high-fat diet rats was higher (8.7%) compared with
      rats on the control diet (6.1%). This was confirmed by electron microscope and
      light microscopy studies. Our results indicate that lipid accumulation in the
      myocardium might be an early indication of the cardiovascular pathophysiology
      associated with type 2 diabetes.

PMID- 23542916
TI  - DiBAC4(3) hits a "sweet spot" for the activation of arterial large-conductance
      Ca2+-activated potassium channels independently of the beta1-subunit.
AB  - The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol
      [DiBAC4(3)] has been reported as a novel large-conductance Ca2+-activated K+ (BK)
      channel activator with selectivity for its beta1- or beta4-subunits. In arterial
      smooth muscle, BK channels are formed by a pore-forming alpha-subunit and a
      smooth muscle-abundant regulatory beta1-subunit. This tissue specificity has
      driven extensive pharmacological research aimed at regulating arterial tone.
      Using animals with a disruption of the gene for the beta1-subunit, we explored
      the effects of DiBAC4(3) in native channels from arterial smooth muscle. We
      tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies
      mostly on its alpha-subunit. We studied BK channels from wild-type and transgenic
      beta1-knockout mice in excised patches. BK channels from brain arteries, with or
      without the beta1-subunit, were similarly activated by DiBAC4(3). In addition, we
      found that saturating concentrations of DiBAC4(3) (~30 MUM) promote an
      unprecedented persistent activation of the channel that negatively shifts its
      voltage dependence by as much as -300 mV. This "sweet spot" for persistent
      activation is independent of Ca2+ and/or the beta1-4-subunits and is fully
      achieved when DiBAC4(3) is applied to the intracellular side of the channel.
      Arterial BK channel response to DiBAC4(3) varies across species and/or vascular
      beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms
      and help in the rational design of BK channel activators.

PMID- 23542918
TI  - Impaired mitochondrial function in chronically ischemic human heart.
AB  - Chronic ischemic heart disease is associated with myocardial hypoperfusion. The
      resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a
      compromised energetic state. Furthermore, ischemic damage may cause excessive
      production of reactive oxygen species (ROS), producing mitochondrial damage,
      hereby reinforcing a vicious circle. Ischemic preconditioning has been proven
      protective in acute ischemia, but the subject of chronic ischemic preconditioning
      has not been explored in humans. We hypothesized that mitochondrial respiratory
      capacity would be diminished in chronic ischemic regions of human myocardium but
      that these mitochondria would be more resistant to ex vivo ischemia and, second,
      that ROS generation would be higher in ischemic myocardium. The aim of this study
      was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to
      investigate ROS production, and finally to assess myocardial antioxidant levels.
      Mitochondrial respiration in biopsies from ischemic and nonischemic regions from
      the left ventricle of the same heart was compared in nine human subjects. Maximal
      oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic
      compared with nonischemic myocardium (P < 0.05), but the degree of coupling
      (respiratory control ratio) did not differ (P > 0.05). The presence of ex vivo
      hypoxia did not reveal any chronic ischemic preconditioning of the ischemic
      myocardial regions (P > 0.05). ROS production was higher in ischemic myocardium
      (P < 0.05), and the levels of antioxidant protein expression was lower.
      Diminished mitochondrial respiration capacity and excessive ROS production
      demonstrate an impaired mitochondrial function in ischemic human heart muscle. No
      chronic ischemic preconditioning effect was found.

PMID- 23542919
TI  - Arcuate nucleus injection of an anti-insulin affibody prevents the sympathetic
      response to insulin.
AB  - Accumulating evidence suggests that insulin acts within the hypothalamus to alter
      sympathetic nerve activity (SNA) and baroreflex function. Although insulin
      receptors are widely expressed across the hypothalamus, recent evidence suggests
      that neurons of the arcuate nucleus (ARC) play an important role in the
      sympathoexcitatory response to insulin. The purpose of the present study was to
      determine whether circulating insulin acts directly in the ARC to elevate SNA. In
      anesthetized male Sprague-Dawley rats (275-425 g), the action of insulin was
      neutralized by microinjection of an anti-insulin affibody (1 ng/40 nl). To verify
      the efficacy of the affibody, ARC pretreatment with injection of the anti-insulin
      affibody completely prevented the increase in lumbar SNA produced by ARC
      injection of insulin. Next, ARC pretreatment with the anti-insulin affibody
      attenuated the lumbar sympathoexcitatory response to intracerebroventricular
      injection of insulin. Third, a hyperinsulinemic-euglycemic clamp increased
      lumbar, but not renal, SNA in animals that received ARC injection of a control
      affibody. However, this sympathoexcitatory response was absent in animals
      pretreated with the anti-insulin affibody in the ARC. Injection of the anti
      insulin affibody in the adjacent ventromedial hypothalamus did not alter the
      sympathoexcitatory response to insulin. The ability of the anti-insulin affibody
      to prevent the sympathetic effects of insulin cannot be attributed to a general
      inactivation or nonspecific effect on ARC neurons as the affibody did not alter
      the sympathoexcitatory response to ARC disinhibition by gabazine. Collectively,
      these findings suggest that circulating insulin acts within the ARC to increase
      SNA.

PMID- 23542920
TI  - Tempol prevents cardiac oxidative damage and left ventricular dysfunction in the
      PPAR-alpha KO mouse.
AB  - Peroxisome proliferator-activated receptor (PPAR)-alpha deletion induces a
      profound decrease in MnSOD activity, leading to oxidative stress and left
      ventricular (LV) dysfunction. We tested the hypothesis that treatment of PPAR
      alpha knockout (KO) mice with the SOD mimetic tempol prevents the heart from
      pathological remodelling and preserves LV function. Twenty PPAR-alpha KO mice and
      20 age-matched wild-type mice were randomly treated for 8 wk with vehicle or
      tempol in the drinking water. LV contractile parameters were determined both in
      vivo using echocardiography and ex vivo using papillary muscle mechanics.
      Translational and posttranslational modifications of myosin heavy chain protein
      as well as the expression and activity of major antioxidant enzymes were
      measured. Tempol treatment did not affect LV function in wild-type mice; however,
      in PPAR-alpha KO mice, tempol prevented the decrease in LV ejection fraction and
      restored the contractile parameters of papillary muscle, including maximum
      shortening velocity, maximum extent of shortening, and total tension. Moreover,
      compared with untreated PPAR-alpha KO mice, myosin heavy chain tyrosine nitration
      and anion superoxide production were markedly reduced in PPAR-alpha KO mice after
      treatment. Tempol also significantly increased glutathione peroxidase and
      glutathione reductase activities (~ 50%) in PPAR-alpha KO mice. In conclusion,
      these findings demonstrate that treatment with the SOD mimetic tempol can prevent
      cardiac dysfunction in PPAR-alpha KO mice by reducing the oxidation of
      contractile proteins. In addition, we show that the beneficial effects of tempol
      in PPAR-alpha KO mice involve activation of the glutathione
      peroxidase/glutathione reductase system.

PMID- 23542921
TI  - Large-conductance Ca2+-activated potassium channel in mitochondria of endothelial
      EA.hy926 cells.
AB  - In the present study, we describe the existence of a large-conductance Ca2+
      activated potassium (BKCa) channel in the mitochondria of the human endothelial
      cell line EA.hy926. A single-channel current was recorded from endothelial
      mitoplasts (i.e., inner mitochondrial membrane) using the patch-clamp technique
      in the mitoplast-attached mode. A potassium-selective current was recorded with a
      mean conductance equal to 270 +/- 10 pS in a symmetrical 150/150 mM KCl isotonic
      solution. The channel activity, which was determined as the open probability,
      increased with the addition of calcium ions and the potassium channel opener
      NS1619. Conversely, the activity of the channel was irreversibly blocked by
      paxilline and iberiotoxin, BKCa channel inhibitors. The open-state probability
      was found to be voltage dependent. The substances known to modulate BKCa channel
      activity influenced the bioenergetics of mitochondria isolated from human
      endothelial EA.hy926 cells. In isolated mitochondria, 100 MUM Ca2+, 10 MUM
      NS1619, and 0.5 MUM NS11021 depolarized the mitochondrial membrane potential and
      stimulated nonphosphorylating respiration. These effects were blocked by
      iberiotoxin and paxilline in a potassium-dependent manner. Under phosphorylating
      conditions, NS1619-induced, iberiotoxin-sensitive uncoupling diverted energy from
      ATP synthesis during the phosphorylating respiration of the endothelial
      mitochondria. Immunological analysis with antibodies raised against proteins of
      the plasma membrane BKCa channel identified a pore-forming alpha-subunit and an
      auxiliary beta2-subunit of the channel in the endothelial mitochondrial inner
      membrane. In conclusion, we show for the first time that the inner mitochondrial
      membrane in human endothelial EA.hy926 cells contains a large-conductance calcium
      dependent potassium channel with properties similar to those of the surface
      membrane BKCa channel.

PMID- 23542922
TI  - Muscle metaboreflex activation speeds the recovery of arterial blood pressure
      following acute hypotension in humans.
AB  - It has been suggested that the arterial baroreflex and muscle metaboreflex are
      both activated during heavy exercise and that they interact to modulate primary
      cardiovascular reflex responses. This proposed interaction and its consequences
      are not fully understood, however. The purpose of present study was to test our
      hypothesis that dynamic arterial baroreflex-mediated cardiovascular responses to
      acute systemic hypotension in humans are augmented when the muscle metaboreflex
      is active and that this results in a faster recovery of arterial blood pressure.
      Acute hypotension was induced nonpharmacologically in 12 healthy subjects by
      releasing bilateral thigh cuffs after 9 min of suprasystolic resting ischemia,
      with and without muscle metaboreflex activation via postexercise muscle ischemia
      (PEMI) after 1 min of isometric handgrip exercise at 50% maximum voluntary
      contraction. The thigh-cuff release evoked rapid reductions in mean arterial
      pressure (MAP) and increases in heart rate, cardiac output (Doppler), and total
      vascular conductance (TVC) under control conditions and during PEMI. The
      reductions in MAP from baseline were greater and the increases in TVC were
      smaller during PEMI than control. In addition, arterial baroreflex-mediated
      peripheral vasoconstriction was augmented during PEMI, as evidenced by a near
      doubling of the rate of recovery of MAP and TVC. These results show that when the
      muscle metaboreflex is activated in humans, arterial baroreflex-mediated
      peripheral vasoconstriction elicited in response to acute hypotension is
      augmented, which halves the time needed for MAP recovery. Such modulation of
      baroreflex function would be advantageous for maintaining an elevated arterial
      blood pressure during activation of the muscle metaboreflex.

PMID- 23542923
TI  - Practical issues for the use of tranexamic acid in total knee arthroplasty: a
      systematic review.
AB  - PURPOSE: This systematic review was undertaken to answer three specific questions
      relating to the clinical values of tranexamic acid (TNA) in total knee
      arthroplasty (TKA): (1) Whether there are differences in blood-saving effects
      between the systemic and topical administrations; (2) Whether blood-saving
      effects of TNA differ by doses and timings of administration; and (3) Whether the
      use of TNA is safe at all reported doses, timings, and routes of administration
      with respect to the incidences of symptomatic deep-vein thrombosis (DVT) and
      pulmonary embolism (PE). METHODS: A systematic review was carried out with 28
      randomised controlled trials to evaluate the efficacy and safety of TNA use in
      TKA identified from the literature. RESULTS: Both systemic and topical
      administrations reduced blood loss after TKA, but transfusion reducing effects
      varied in studies whether systemic or topical administrations. The effects of TNA
      were influenced by doses and timings of administration. No increased incidences
      of symptomatic DVT and PE were found for all reported doses, timings, and routes
      of TNA administration. CONCLUSION: Surgeons can consider incorporating the use of
      TNA to their blood-saving protocols in TKA without serious concern of adverse
      events but need to adopt optimal doses, timings, and routes of TNA
      administrations.

PMID- 23542925
TI  - Electrochemical removal of metallic implants from Technovit 9100 New embedded
      hard and soft tissues prior to histological sectioning.
AB  - Solid metallic implants in soft or hard tissues are serious challenges for
      histological processing. However, metallic implants are more frequently used in
      e.g. cardiovascular or orthopaedic therapies. Before clinical use, these devices
      need to be tested thoroughly in a biological environment and histological
      analysis of their biocompatibility is a major requirement. To allow the
      histological analysis of metallic implants in tissues especially in calcified
      hard tissues, we describe a method for embedding these tissues in the resin
      Technovit 9100 New and removing the metallic implants by electrochemical
      dissolution. With the combination of these two processes, we are able to achieve
      5 MUm thick sections from soft or hard tissues with a superior preservation of
      tissue architecture and especially the implant-tissue interface. These sections
      can be stained by classical stainings, immunohistochemical and
      enzymehistochemical as well as DNA-based staining methods. 

PMID- 23542924
TI  - Generation of somatic electromechanical force by outer hair cells may be
      influenced by prestin-CASK interaction at the basal junction with the Deiter's
      cell.
AB  - The motor protein, prestin, situated in the basolateral plasma membrane of
      cochlear outer hair cells (OHCs), underlies the generation of somatic, voltage
      driven mechanical force, the basis for the exquisite sensitivity, frequency
      selectivity and dynamic range of mammalian hearing. The molecular and structural
      basis of the ontogenetic development of this electromechanical force has remained
      elusive. The present study demonstrates that this force is significantly reduced
      when the immature subcellular distribution of prestin found along the entire
      plasma membrane persists into maturity, as has been described in previous studies
      under hypothyroidism. This observation suggests that cochlear amplification is
      critically dependent on the surface expression and distribution of prestin.
      Searching for proteins involved in organizing the subcellular localization of
      prestin to the basolateral plasma membrane, we identified cochlear expression of
      a novel truncated prestin splice isoform named prestin 9b (Slc26A5d) that
      contains a putative PDZ domain-binding motif. Using prestin 9b as the bait in a
      yeast two-hybrid assay, we identified a calcium/calmodulin-dependent serine
      protein kinase (CASK) as an interaction partner of prestin. Co
      immunoprecipitation assays showed that CASK and prestin 9b can interact with full
      length prestin. CASK was co-localized with prestin in a membrane domain where
      prestin-expressing OHC membrane abuts prestin-free OHC membrane, but was absent
      from this area for thyroid hormone deficiency. These findings suggest that CASK
      and the truncated prestin splice isoform contribute to confinement of prestin to
      the basolateral region of the plasma membrane. By means of such an interaction,
      the basal junction region between the OHC and its Deiter's cell may contribute to
      efficient generation of somatic electromechanical force. 

PMID- 23542926
TI  - Uptake and localisation of small-molecule fluorescent probes in living cells: a
      critical appraisal of QSAR models and a case study concerning probes for DNA and
      RNA.
AB  - Small-molecule fluorochromes are used in biology and medicine to generate
      informative microscopic and macroscopic images, permitting identification of cell
      structures, measurement of physiological/physicochemical properties, assessment
      of biological functions and assay of chemical components. Modes of uptake and
      precise intracellular localisation of a probe are typically significant factors
      in its successful application. These processes and localisations can be predicted
      using quantitative structure activity relations (QSAR) models, which correlate
      aspects of the physicochemical properties of the probes (expressed numerically)
      with the uptake/localisation. Pay-offs of such modelling include better
      understanding and trouble-shooting of current and novel probes, and easier design
      of future probes ("guided synthesis"). Uptake models discussed consider
      adsorptive (to lipid or protein domains), phagocytic and pinocytotic endocytosis,
      as well as passive diffusion. Localisation models discussed include those for
      cytosol, endoplasmic reticulum, Golgi apparatus, lipid droplets, lysosomes,
      mitochondria, nucleus and plasma membrane. A case example illustrates how such
      QSAR modelling of probe interactions can clarify localisation and mode of binding
      of probes to intracellular nucleic acids of living cells, including not only
      eukaryotic chromatin DNA and ribosomal RNA, but also prokaryote chromosomes.

PMID- 23542929
TI  - Physics and engineering aspects of cell and tissue imaging systems: microscopic
      devices and computer assisted diagnosis.
AB  - The conventional optical microscopes have been used widely in scientific research
      and in clinical practice. The modern digital microscopic devices combine the
      power of optical imaging and computerized analysis, archiving and communication
      techniques. It has a great potential in pathological examinations for improving
      the efficiency and accuracy of clinical diagnosis. This chapter reviews the basic
      optical principles of conventional microscopes, fluorescence microscopes and
      electron microscopes. The recent developments and future clinical applications of
      advanced digital microscopic imaging methods and computer assisted diagnosis
      schemes are also discussed.

PMID- 23542928
TI  - Can recumbent magnetic resonance imaging replace myelography or computed
      tomography myelography for detecting lumbar spinal stenosis?
AB  - OBJECTIVE: To compare the diagnostic efficacy of recumbent magnetic resonance
      imaging (MRI), computed tomography myelography (CTM), and myelography, with
      regard to indications for surgery for lumbar stenosis. BACKGROUND DATA: In
      patients with lumbar spinal stenosis-like disorders, small compressions are
      sometimes observed in magnetic resonance images acquired in the recumbent
      position, leading to potential misdiagnosis. Few prospective studies have
      compared the diagnostic accuracy of MRI, myelography, and CTM. Therefore, it is
      not clear whether myelography is necessary or not. METHODS: Fifty-four patients
      fulfilled the criteria. All patients underwent MRI, myelography, and CTM. MRI was
      performed with the patient in a normal recumbent position, and CTM was performed
      with the patients in both a recumbent and extended positions. All patients
      underwent surgery for lumbar spinal stenosis. Findings from visual examinations
      (sagittal images of MR, axial images of MR, axial reconstruction images of CTM
      and myelograms) were defined as compression + or -. We analyzed the sensitivity
      of the different examinations for diagnosis and the relationship among the types
      of images. RESULTS: Sensitivity was as follows: CTM 94.4 %, myelography 87.0 %,
      and MRI 75.9 %. In myelography, the images of 37 patients were worsened by
      dynamic synthesis (Dyn+). Among patients without compression on MRI, 11 showed
      compression on myelography. Of these 11, 8 of these patients were Dyn+, and 2
      patients showed compression on myelography, but not on CTM and were Dyn+. Thus,
      some compression can be revealed only with myelography. CTM was more sensitive
      than axial MRI and showed compression in 12 patients that was not detected by
      axial MRI. CONCLUSION: Myelography revealed stenosis that was not detected by
      MRI. CTM with extension is more sensitive for detecting stenosis than MRI.
      Recumbent MRI cannot replace myelography or CTM in terms of dynamic findings and
      sensitivity.

PMID- 23542927
TI  - Prefrontal cortical kappa-opioid receptor modulation of local neurotransmission
      and conditioned place aversion.
AB  - Kappa-opioid receptors (KORs) are important for motivation and other medial
      prefrontal cortex (mPFC)-dependent behaviors. Although KORs are present in the
      mPFC, their role in regulating transmission in this brain region and their
      contribution to KOR-mediated aversion are not known. Using in vivo microdialysis
      in rats and mice, we demonstrate that intra-mPFC administration of the selective
      KOR agonist U69,593 decreased local dopamine (DA) overflow, while reverse
      dialysis of the KOR antagonist nor-Binaltorphimine (nor-BNI) enhanced mPFC DA
      overflow. Extracellular amino-acid levels were also affected by KORs, as U69,593
      reduced glutamate and GABA levels driven by the glutamate reuptake blocker, l
      trans-pyrrolidine-2,4-dicarboxylate. Whole-cell recordings from mPFC layer V
      pyramidal neurons revealed that U69,593 decreased the frequency, but not
      amplitude, of glutamatergic mini EPSPs. To determine whether KOR regulation of
      mPFC DA overflow was mediated by KOR on DA terminals, we utilized a Cre
      recombinase-driven mouse line lacking KOR in DA neurons. In these mice, basal DA
      release or uptake was unaltered relative to controls, but attenuation of mPFC DA
      overflow by local U69,593 was not observed, indicating KOR acts directly on mPFC
      DA terminals to locally inhibit DA levels. Conditioning procedures were then used
      to determine whether mPFC KOR signaling was necessary for KOR-mediated aversion.
      U69,593-mediated conditioned place aversion was blocked by intra-mPFC nor-BNI
      microinjection. These findings demonstrate that mPFC KORs negatively regulate DA
      and amino-acid neurotransmission, and are necessary for KOR-mediated aversion. 

PMID- 23542930
TI  - Advanced methods in fluorescence microscopy.
AB  - It requires a good deal of will power to resist hyperbole in considering the
      advances that have been achieved in fluorescence microscopy in the last 25 years.
      Our effort has been to survey the modalities of microscopic fluorescence imaging
      available to cell biologists and perhaps useful for diagnostic pathologists. The
      gamut extends from established confocal laser scanning through multiphoton and
      TIRF to the emerging technologies of super-resolution microscopy that breech the
      Abbe limit of resolution. Also considered are the recent innovations in
      structured and light sheet illumination, the use of FRET and molecular beacons
      that exploit specific characteristics of designer fluorescent proteins,
      fluorescence speckles, and second harmonic generation for native anisometric
      structures like collagen, microtubules and sarcomeres.

PMID- 23542931
TI  - Spectral imaging in preclinical research and clinical pathology.
AB  - Spectral imaging methods are attracting increased interest from researchers and
      practitioners in basic science, preclinical and clinical arenas. A combination of
      better labeling reagents and better optics creates opportunities to detect and
      measure multiple parameters at the molecular and cellular level. These tools can
      provide valuable insights into the basic mechanisms of life, and yield diagnostic
      and prognostic information for clinical applications. There are many
      multispectral technologies available, each with its own advantages and
      limitations. This chapter will present an overview of the rationale for spectral
      imaging, and discuss the hardware, software and sample labeling strategies that
      can optimize its usefulness in clinical settings.

PMID- 23542932
TI  - Automated image interpretation and computer-assisted diagnostics.
AB  - Much of the difficulty in reaching consistent evaluations of radiology and
      pathology imaging studies arises from subjective impressions of individual
      observers. Developing strategies that can reliably transform complex visual
      observations into well-defined algorithmic procedures is an active area of
      exploration which can advance clinical practice, investigative research and
      outcome studies. The literature shows that when characterizations are based upon
      computer-aided analysis, objectivity, reproducibility and sensitivity improve
      considerably. Advanced imaging and computational tools could potentially enable
      investigators to detect and track subtle changes in measurable parameters leading
      to the discovery of novel diagnostic and prognostic clues which are not apparent
      by human visual inspection alone. The overarching objective of this book chapter
      is to provide readers with a summary of the origin, evolution and future
      directions for the fields of automated image interpretation and computer-assisted
      diagnostics. The chapter begins with a high-level overview of the fields of image
      processing, pattern recognition, and computer vision followed by a description of
      how these disciplines relate to the more comprehensive fields of computer
      assisted diagnostics and image guided decision support. Throughout the remainder
      of the chapter we have supplied multiple illustrative examples demonstrating how
      recent advances and innovations in each of these areas have impacted clinical and
      research activities throughout pathology and radiology including high-throughput
      tissue microarray analysis, multi-spectral imaging, and image co-registration.

PMID- 23542933
TI  - Optical coherence tomography for rapid tissue screening and directed histological
      sectioning.
AB  - In pathology, histological examination of the tissue is the "gold standard" to
      diagnose various diseases. It has contributed significantly toward identifying
      the abnormalities in tissues and cells, but has inherent drawbacks when used for
      fast and accurate diagnosis. These limitations include the lack of in vivo
      observation in real time and sampling errors due to limited number and area
      coverage of tissue sections. Its diagnostic yield also varies depending on the
      ability of the physician and the effectiveness of any image guidance technique
      that may be used for tissue screening during excisional biopsy. In order to
      overcome these current limitations of histology-based diagnostics, there are
      significant needs for either complementary or alternative imaging techniques
      which perform non-destructive, high resolution, and rapid tissue screening.
      Optical coherence tomography (OCT) is an emerging imaging modality which allows
      real-time cross-sectional imaging with high resolutions that approach those of
      histology. OCT could be a very promising technique which has the potential to be
      used as an adjunct to histological tissue observation when it is not practical to
      take specimens for histological processing, when large areas of tissue need
      investigating, or when rapid microscopic imaging is needed. This review will
      describe the use of OCT as an image guidance tool for fast tissue screening and
      directed histological tissue sectioning in pathology.

PMID- 23542934
TI  - Nuclear morphology measurements with angle-resolved low coherence interferometry
      for application to cell biology and early cancer detection.
AB  - The study of intact, living cells using non-invasive optical spectroscopic
      methods offers the opportunity to assess cellular structure and organization in a
      way that is not possible with commonly used cell biology imaging techniques. We
      have developed a novel spectroscopic technique for diagnosing disease at the
      cellular level based on using low-coherence interferometry (LCI) to detect the
      angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the
      ability of LCI to isolate scattering from sub-surface tissue layers with the
      ability of light scattering spectroscopy to obtain structural information on sub
      wavelength scales. In application to examining cellular structure, a/LCI enables
      quantitative measurements of changes in the size and texture of cell nuclei.
      These quantitative measurements are characteristic of different pathological
      states. The capabilities of a/LCI were demonstrated using a clinical system that
      can be applied in endoscopic surveillance of esophageal tissue, producing high
      sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments
      with in vitro cell samples also show the utility of a/LCI in observing structural
      changes due to environmental stimuli as well as detecting apoptosis due to
      chemotherapeutic agents.

PMID- 23542935
TI  - Magnetic resonance microscopy.
AB  - MRI, one of the major clinical imaging modalities, has gained an important role
      in studying small animal models, e.g., rats and mice. But imaging rodents comes
      with challenges, since the image resolution needs to be ~ 3000-times higher to
      resolve anatomical details at a level comparable to clinical imaging. A
      resolution on the order of 100 microns or less redefines MR imaging as MR
      microscopy. We discuss in this chapter the basic components of the MR imaging
      chain, with a particular emphasis on small animal imaging demands: from hardware
      design to basic physical principles of MR image formation, and contrast
      mechanisms. We discuss special considerations of animal preparation for imaging,
      and staining methods to enhance contrast. Attention is given to factors that
      increase sensitivity, including exogenous contrast agents, high performance
      radiofrequency detectors, and advanced MR encoding sequences. Among these,
      diffusion tensor imaging and tractography add novel information on white matter
      tracts, helping to better understand important aspects of development and
      neurodegeneration. These developments open avenues for efficient phenotyping of
      small animal models, in vivo - to include anatomical as well as functional
      estimates, or ex-vivo - with exquisite anatomical detail. The need for higher
      resolution results in larger image arrays that need to be processed efficiently.
      We discuss image-processing approaches for quantitative characterization of
      animal cohorts, and building population atlases. High throughput is essential for
      these methods to become practical. We discuss current trends for increasing
      detector performance, the use of cryoprobes, as well as strategies for imaging
      multiple animals at the same time. Ultimately, the development of highly specific
      probes, with the possibility to be used in multimodal imaging, will offer new
      insights into histology. MRM, alone or in combination with other imaging
      modalities, will increase the knowledge of fundamental biological processes, help
      understanding the genetic basis of human diseases, and test pharmacological
      interventions.

PMID- 23542936
TI  - Impedance measurements in the biomedical sciences.
AB  - Biological organisms and their component organs, tissues and cells have unique
      electrical impedance properties. Impedance properties often change with changes
      in structure, composition, and metabolism, and can be indicative of the onset and
      progression of disease states. Over the past 100 years, instruments and
      analytical methods have been developed to measure the impedance properties of
      biological specimens and to utilize these measurements in both clinical and basic
      science settings. This chapter will review the applications of impedance
      measurements in the biomedical sciences, from whole body analysis to impedance
      measurements of single cells and cell monolayers, and how cellular impedance
      measuring instruments can now be used in high throughput screening applications.

PMID- 23542937
TI  - Raman scattering in pathology.
AB  - Raman scattering is the inelastic scattering of light by chemical bonds, and can
      therefore show molecular specificity. It can be used both in pure spectroscopy
      mode, and in imaging mode. While many applications of Raman spectroscopy and
      imaging in the biomedical field have been so far demonstrated, the use of this
      technology for pathology applications is still in its early stages. In this paper
      we review some of the most important recent developments in this field, including
      a description of relevant technologies, applications to molecular sensing,
      characterization of cells and tissues of interest, and disease detection via
      Raman scattering.

PMID- 23542938
TI  - Real-time pathology through in vivo microscopy.
AB  - Miniature microscopes are being developed to examine tissue in situ for early
      anatomic and molecular indicators of disease, in real time, and at cellular
      resolution. These new devices will lead to a shift from the current diagnostic
      paradigm of biopsy followed by histopathology and recommended therapy, to one of
      non-invasive point-of-care diagnosis with the possibility of treatment in the
      same session. This potential revolution in disease management may have a major
      impact on the training of future physicians to include the use and interpretation
      of real-time in vivo microscopic data, and will also affect the emerging fields
      of telepathology and telemedicine. Implementation of new technologies into
      clinical practice is a complex process that requires multidisciplinary
      communication and collaboration among clinicians, engineers and scientists. As
      such, our aim is to provide a forward-looking view of the critical issues facing
      the development of new technologies and directing clinical education. Here, we
      focus on the use of in vivo microscopy for detection of malignant and pre
      malignant lesions as well as for guiding therapy. We will highlight some of the
      areas in which in vivo microscopy could address unmet clinical needs, and then
      review the technological challenges that are being addressed, or need to be
      addressed, for in vivo microscopy to become an effective clinical tool.

PMID- 23542939
TI  - Biophotonics techniques for structural and functional imaging, in vivo.
AB  - In vivo optical imaging is being conducted in a variety of medical applications,
      including optical breast cancer imaging, functional brain imaging, endoscopy,
      exercise medicine, and monitoring the photodynamic therapy and progress of
      neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical
      breast cancer imaging has shown promising results in cancer detection, and
      monitoring the progress of neoadjuvant chemotherapy. The use of near infrared
      spectroscopy for functional brain imaging has been growing rapidly. In
      fluorescence imaging, the difference between autofluorescence of cancer lesions
      compared to normal tissues were used in endoscopy to distinguish malignant
      lesions from normal tissue or inflammation and in determining the boarders of
      cancer lesions in surgery. Recent advances in drugs targeting specific tumor
      receptors, such as monoclonal antibodies (mAb), has created a new demand for
      developing non-invasive in vivo imaging techniques for detection of cancer
      biomarkers, and for monitoring their down regulations during therapy. Targeted
      treatments, combined with new imaging techniques, are expected to potentially
      result in new imaging and treatment paradigms in cancer therapy. Similar
      approaches can potentially be applied for the characterization of other disease
      related biomarkers. In this chapter, we provide a review of diffuse optical and
      fluorescence imaging techniques with their application in functional brain
      imaging and cancer diagnosis.

PMID- 23542940
TI  - Lensfree computational microscopy tools for cell and tissue imaging at the point
      of-care and in low-resource settings.
AB  - The recent revolution in digital technologies and information processing methods
      present important opportunities to transform the way optical imaging is
      performed, particularly toward improving the throughput of microscopes while at
      the same time reducing their relative cost and complexity. Lensfree computational
      microscopy is rapidly emerging toward this end, and by discarding lenses and
      other bulky optical components of conventional imaging systems, and relying on
      digital computation instead, it can achieve both reflection and transmission mode
      microscopy over a large field-of-view within compact, cost-effective and
      mechanically robust architectures. Such high throughput and miniaturized imaging
      devices can provide a complementary toolset for telemedicine applications and
      point-of-care diagnostics by facilitating complex and critical tasks such as
      cytometry and microscopic analysis of e.g., blood smears, Papanicolaou (Pap)
      tests and tissue samples. In this article, the basics of these lensfree
      microscopy modalities will be reviewed, and their clinically relevant
      applications will be discussed.

PMID- 23542941
TI  - The evolution of anatomic pathology: new strategies and emerging trends.
AB  - Science advances both by conceptual leaps and by improved observational and
      analytic tools. Mechanism and function in biological systems can best be
      understood in the context of the complex microenvironments in which they occur,
      and for this purpose morphologic analysis can be critical. The technological
      advances in cell and tissue imaging described in this book are currently finding
      application in a wide variety of basic, translational, and clinical biomedical
      studies. We have chosen some specific approaches that illustrate the various
      categories of imaging methodologies available. Many other ways of applying modern
      morphology-based interrogation of cells and tissues have already been described
      and are continuously evolving. This chapter provides examples of some of these.
      On the clinical front, radiologists have embraced new imaging technique to a
      greater extent than have pathologists. This chapter discusses some of the factors
      responsible for this, and suggests that pathology and radiology are converging
      towards a more holistic approach to diagnostic imaging.

PMID- 23542944
TI  - Studies in Health Technology and Informatics. Biophotonics in pathology. Preface.

PMID- 23542945
TI  - A survey on intrabody communications for body area network applications.
AB  - The rapid increase in healthcare demand has seen novel developments in health
      monitoring technologies, such as the body area networks (BAN) paradigm. BAN
      technology envisions a network of continuously operating sensors, which measure
      critical physical and physiological parameters e.g., mobility, heart rate, and
      glucose levels. Wireless connectivity in BAN technology is key to its success as
      it grants portability and flexibility to the user. While radio frequency (RF)
      wireless technology has been successfully deployed in most BAN implementations,
      they consume a lot of battery power, are susceptible to electromagnetic
      interference and have security issues. Intrabody communication (IBC) is an
      alternative wireless communication technology which uses the human body as the
      signal propagation medium. IBC has characteristics that could naturally address
      the issues with RF for BAN technology. This survey examines the on-going research
      in this area and highlights IBC core fundamentals, current mathematical models of
      the human body, IBC transceiver designs, and the remaining research challenges to
      be addressed. IBC has exciting prospects for making BAN technologies more
      practical in the future. 

PMID- 23542946
TI  - Fibromyalgia and breast cancer.

PMID- 23542947
TI  - Overexpression of AIB1 correlates inversely with E-cadherin expression in
      pancreatic adenocarcinoma and may promote lymph node metastasis.
AB  - BACKGROUND: It was reported that the nuclear receptor coactivator amplified in
      breast cancer1 (AIB1) could regulate cancer cell invasion and migration in a
      nuclear receptor signaling-independent manner. Meanwhile, the process of
      epithelial mesenchymal transition (EMT) is critical for tumor invasion and
      metastasis. The present study aimed to determine the role of AIB1 and EMT markers
      in human pancreatic adenocarcinoma. METHODS: AIB1, ZO-1, E-cadherin, vimentin,
      and N-cadherin protein expression in 76 pancreatic adenocarcinomas were assessed
      using immunohistochemistry and analyzed for clinicopathological significance.
      RESULTS: The frequency of AIB1 overexpression in pancreatic adenocarcinomas with
      lymph node metastasis is 68 % (19/28), which is significantly higher than in
      pancreatic adenocarcinomas without lymph node metastasis (42 %; 20/48). In
      addition, the frequency of low expression of E-cadherin in pancreatic carcinomas
      with lymph node metastasis (68 %; 19/28) was significantly higher than in tumors
      without lymph node metastasis (44 %; 21/48). Correlation analysis demonstrated
      that the overexpression of AIB1 was inversely correlated with low expression of E
      cadherin in pancreatic adenocarcinomas. CONCLUSION: Overexpression of AIB1 might
      promote invasion and metastasis of cancer cells and is associated with down
      regulation of E-cadherin in pancreatic adenocarcinomas.

PMID- 23542948
TI  - Investigation of parasitic and bacterial diseases in pigs with analysis of
      hematological and serum biochemical profile.
AB  - The present study was undertaken to evaluate various disease conditions prevalent
      in slaughtered pigs and zoonotic importance. The study was conducted on two
      hundred non-descript pigs slaughtered at an organized slaughter house, Mumbai.
      The animals included in the study were randomly selected. Post mortem examination
      of the animals was performed to note various disease conditions and tissues were
      collected for histopathology. Direct examination of stool was found negative for
      parasites. Gross and microscopical examination revealed presence of Ascarops
      strongylina, Sarcocyst, Hydatid cyst, Cysticercus cellulosae, Ascaris suum and
      Cysticercus tenuicollis, along with bacteria like Salmonella, Pseudomonas,
      Shigella, Streptococci, Proteus and Pasteurella spp. were isolated. Indirect
      ELISA was performed for detection of antibody titer in the pig serum against
      classical swine fever. Studies on hematological and serum biochemical profile
      revealed decreased total protein concentration and globulin level with
      leukocytosis and neutrophilia and in parasitic infections eosinophilia was
      evident.

PMID- 23542949
TI  - Brain fingerprinting: a comprehensive tutorial review of detection of concealed
      information with event-related brain potentials.
AB  - Brain fingerprinting (BF) detects concealed information stored in the brain by
      measuring brainwaves. A specific EEG event-related potential, a P300-MERMER, is
      elicited by stimuli that are significant in the present context. BF detects P300
      MERMER responses to words/pictures relevant to a crime scene, terrorist training,
      bomb-making knowledge, etc. BF detects information by measuring cognitive
      information processing. BF does not detect lies, stress, or emotion. BF computes
      a determination of "information present" or "information absent" and a
      statistical confidence for each individual determination. Laboratory and field
      tests at the FBI, CIA, US Navy and elsewhere have resulted in 0% errors: no false
      positives and no false negatives. 100% of determinations made were correct. 3% of
      results have been "indeterminate." BF has been applied in criminal cases and
      ruled admissible in court. Scientific standards for BF tests are discussed.
      Meeting the BF scientific standards is necessary for accuracy and validity.
      Alternative techniques that failed to meet the BF scientific standards produced
      low accuracy and susceptibility to countermeasures. BF is highly resistant to
      countermeasures. No one has beaten a BF test with countermeasures, despite a
      $100,000 reward for doing so. Principles of applying BF in the laboratory and the
      field are discussed.

PMID- 23542950
TI  - Burn depth analysis using multidimensional scaling applied to psychophysical
      experiment data.
AB  - In this paper a psychophysical experiment and a multidimensional scaling (MDS)
      analysis are undergone to determine the physical characteristics that physicians
      employ to diagnose a burn depth. Subsequently, these characteristics are
      translated into mathematical features, correlated with these physical
      characteristics analysis. Finally, a study to verify the ability of these
      mathematical features to classify burns is performed. In this study, a space with
      axes correlated with the MDS axes has been developed. 74 images have been
      represented in this space and a k-nearest neighbor classifier has been used to
      classify these 74 images. A success rate of 66.2% was obtained when classifying
      burns into three burn depths and a success rate of 83.8% was obtained when burns
      were classified as those which needed grafts and those which did not. Additional
      studies have been performed comparing our system with a principal component
      analysis and a support vector machine classifier. Results validate the ability of
      the mathematical features extracted from the psychophysical experiment to
      classify burns into their depths. In addition, the method has been compared with
      another state-of-the-art method and the same database.

PMID- 23542951
TI  - Blind compressive sensing dynamic MRI.
AB  - We propose a novel blind compressive sensing (BCS) frame work to recover dynamic
      magnetic resonance images from undersampled measurements. This scheme models the
      dynamic signal as a sparse linear combination of temporal basis functions, chosen
      from a large dictionary. In contrast to classical compressed sensing, the BCS
      scheme simultaneously estimates the dictionary and the sparse coefficients from
      the undersampled measurements. Apart from the sparsity of the coefficients, the
      key difference of the BCS scheme with current low rank methods is the
      nonorthogonal nature of the dictionary basis functions. Since the number of
      degrees-of-freedom of the BCS model is smaller than that of the low-rank methods,
      it provides improved reconstructions at high acceleration rates. We formulate the
      reconstruction as a constrained optimization problem; the objective function is
      the linear combination of a data consistency term and sparsity promoting l1 prior
      of the coefficients. The Frobenius norm dictionary constraint is used to avoid
      scale ambiguity. We introduce a simple and efficient majorize-minimize algorithm,
      which decouples the original criterion into three simpler subproblems. An
      alternating minimization strategy is used, where we cycle through the
      minimization of three simpler problems. This algorithm is seen to be considerably
      faster than approaches that alternates between sparse coding and dictionary
      estimation, as well as the extension of K-SVD dictionary learning scheme. The use
      of the l1 penalty and Frobenius norm dictionary constraint enables the
      attenuation of insignificant basis functions compared to the l0 norm and column
      norm constraint assumed in most dictionary learning algorithms; this is
      especially important since the number of basis functions that can be reliably
      estimated is restricted by the available measurements. We also observe that the
      proposed scheme is more robust to local minima compared to K-SVD method, which
      relies on greedy sparse coding. Our phase transition experiments demonstrate that
      the BCS scheme provides much better recovery rates than classical Fourier-based
      CS schemes, while being only marginally worse than the dictionary aware setting.
      Since the overhead in additionally estimating the dictionary is low, this method
      can be very useful in dynamic magnetic resonance imaging applications, where the
      signal is not sparse in known dictionaries. We demonstrate the utility of the BCS
      scheme in accelerating contrast enhanced dynamic data. We observe superior
      reconstruction performance with the BCS scheme in comparison to existing low rank
      and compressed sensing schemes.

PMID- 23542953
TI  - Perceptual quality-regulable video coding system with region-based rate control
      scheme.
AB  - In this paper, we discuss a region-based perceptual quality-regulable H.264 video
      encoder system that we developed. The ability to adjust the quality of specific
      regions of a source video to a predefined level of quality is an essential
      technique for region-based video applications. We use the structural similarity
      index as the quality metric for distortion-quantization modeling and develop a
      bit allocation and rate control scheme for enhancing regional perceptual quality.
      Exploiting the relationship between the reconstructed macroblock and the best
      predicted macroblock from mode decision, a novel quantization parameter
      prediction method is built and used to achieve the target video quality of the
      processed macroblock. Experimental results show that the system model has only
      0.013 quality error in average. Moreover, the proposed region-based rate control
      system can encode video well under a bitrate constraint with a 0.1% bitrate error
      in average. For the situation of the low bitrate constraint, the proposed system
      can encode video with a 0.5% bit error rate in average and enhance the quality of
      the target regions.

PMID- 23542954
TI  - Randomized controlled trial of a clinic-based survivorship intervention following
      adjuvant therapy in breast cancer survivors.
AB  - In 2006, the IOM released a report citing the importance of "survivorship plans"
      to improve quality of life and care coordination for cancer survivors, but little
      has been done to evaluate their efficacy. Women with early-stage breast cancer
      were randomized within 6 weeks of completing adjuvant therapy to a survivorship
      intervention group (SI) or control group (CG). All subjects were given the NCI
      publication, "Facing Forward: Life after Cancer Treatment." The SI also met with
      a nurse/nutritionist to receive a treatment summary, surveillance, and lifestyle
      recommendations. Both groups completed questionnaires on the impact of cancer
      (IOC), patient satisfaction (FACIT-TS-PS), and assessment of survivor concerns
      (ASC) at baseline, 3 and 6 months. Within and between group t tests and linear
      regression analyses were performed. Among 126 women (60 CG, 66 SI), mean age was
      54 years, 48 % were Hispanic, and the groups were well-balanced by baseline
      characteristics. No significant differences between the CG and SI on the FACIT-TS
      PS or IOC at 3 and 6 months were seen. The ASC health worry subscale was lower
      (less worry) in the SI compared to CG (p = 0.02). At all time-points, Hispanic
      women had higher (worse) health worry (p = 0.0008), social-life interference (p =
      0.009), and meaning of cancer scales (p = 0.0004), and more trust in medical
      professionals (p = 0.03) compared to non-Hispanic women. While the SI did not
      lead to significant improvements in most patient-reported outcomes, it was
      associated with decreased health worry. Future interventions should determine the
      most efficient and effective method for delivering survivorship care plans.

PMID- 23542952
TI  - Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis
      and airway surface liquid volume depletion.
AB  - Mucus clearance is an important component of the lung's innate defense system. A
      failure of this system brought on by mucus dehydration is common to both cystic
      fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance
      rates are regulated by the volume of airway surface liquid (ASL) and by ciliary
      beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be
      beneficial to both CF and COPD patients. However, chronic macrolide usage may
      induce bacterial resistance. We have developed a novel macrolide, 2'-desoxy-9-(S)
      erythromycylamine (GS-459755), that has significantly diminished antibiotic
      activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella
      catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in
      chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by
      activating the epithelial sodium channel (ENaC), we tested the ability of GS
      459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on
      HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL
      volume depletion in human bronchial epithelial cells (HBECs). The effect of GS
      459755 on ASL volume was dose dependent (IC50 ~3.9 MUM) and comparable to the
      antibacterial macrolide azithromycin (IC50 ~2.4 MUM). Macrolides had no
      significant effect on CBF or on transepithelial water permeability. However, the
      amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was
      diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE
      induced activation of ENaC and may be useful for the treatment of mucus
      dehydration in CF and COPD without inducing bacterial resistance.

PMID- 23542955
TI  - A meta-analysis of anastrozole in combination with fulvestrant in the first line
      treatment of hormone receptor positive advanced breast cancer.
AB  - Fulvestrant is a highly active systemic therapy in patients with metastatic
      hormone receptor positive breast cancer. Preclinical work suggested potential
      synergy of fulvestrant in combination with aromatase inhibitor therapy and
      delayed development of endocrine resistance. The purpose of this meta-analysis is
      to evaluate the effectiveness of fulvestrant plus anastrozole, compared to
      anastrozole alone, as first line treatment of postmenopausal stage IV hormone
      receptor positive, HER2-negative breast cancer. The literature search was
      performed using PubMed, Google Scholar, Embase, ASCO, and ESMO to search for
      abstracts published during the last 10 years using relevant keywords. Two
      prospective randomized clinical trials were found to fulfill the search criteria
      for combination of anastrozole plus fulvestrant versus anastrozole alone. Meta
      estimates were calculated by combining study estimates using the DerSimonian and
      Laird random effects model. The linear mixed-effects model was used to generate
      95 % prediction intervals (PIs) for study-specific hazard and odds ratios. Pooled
      hazard ratio for progression-free survival is 0.88 (95 % CI 0.72-1.09, 95 % PI
      0.65-1.21), overall survival 0.88 (95 % CI 0.72-1.08, 95 % PI 0.68-1.14) and
      pooled odds ratio for response rate is 1.13 (95 % CI 0.79-1.63, 95 % PI 0.78
      1.65). A non-significant trend was observed with anastrozole plus fulvestrant
      being only marginally better than anastrozole alone in the endpoints of:
      progression-free survival, overall survival, and response rates. Based on these
      data, there is not solid evidence that the addition of fulvestrant at a dose of
      250 mg monthly is better than anastrozole alone as first line therapy in women
      with postmenopausal hormone receptor positive breast cancer.

PMID- 23542956
TI  - The use of neoadjuvant platinum-based chemotherapy in locally advanced breast
      cancer that is triple negative: retrospective analysis of 144 patients.
AB  - Triple-negative breast cancers comprise about 20 % of breast cancers. They have
      poor prognosis and have no standard therapy. The aim of this study was to
      evaluate pathologic complete response (pCR), progression-free survival (PFS), and
      overall survival (OS) in patients with TNBC treated with neoadjuvant platinum
      based chemotherapy. This is a retrospective study of one hundred and forty-four
      women with TNBC treated with neoadjuvant platinum-containing chemotherapy for
      locally advanced breast cancer at the University of Miami between January 1,
      1999, and January 1, 2011. The medical record was reviewed to obtain data on
      clinical characteristics, including ethnicity, race, age, clinical stage,
      treatment regimen, and vital status. This study was approved by the University of
      Miami IRB. All patients had locally advanced breast cancer with at least one of
      the following features at presentation: T3, T4, N2, and N3. The mean tumor size
      by palpation was 9.4 cm. The clinical T-stage at presentation was 1.4 % T1, 8.3 %
      T2, 52.8 % T3, and 37.5 % T4 (19.4 % T4d). The nodal status by physical exam at
      presentation was 23 % N0, 37.5 % N1, 34 % N2, and 5.5 % N3. pCR in breast and
      axilla was seen in 31 %. PFS and OS were 55 and 59 %, respectively, at 7 years.
      Cisplatin offered a survival advantage over carboplatin in both PFS (P = 0.007)
      and OS (P = 0.018). Node positivity was the most important predictor of survival.
      Cisplatin/docetaxel neoadjuvant therapy was well tolerated and an effective
      therapy in locally advanced TNB.

PMID- 23542959
TI  - Knowledge representation and management enabling intelligent interoperability -
      principles and standards.
AB  - Based on the paradigm changes for health, health services and underlying
      technologies as well as the need for at best comprehensive and increasingly
      automated interoperability, the paper addresses the challenge of knowledge
      representation and management for medical decision support. After introducing
      related definitions, a system-theoretical, architecture-centric approach to
      decision support systems (DSSs) and appropriate ways for representing them using
      systems of ontologies is given. Finally, existing and emerging knowledge
      representation and management standards are presented. The paper focuses on the
      knowledge representation and management part of DSSs, excluding the reasoning
      part from consideration.

PMID- 23542957
TI  - Adjuvant endocrine therapy initiation and persistence in a diverse sample of
      patients with breast cancer.
AB  - Adjuvant endocrine therapy for breast cancer reduces recurrence and improves
      survival rates. Many patients never start treatment or discontinue prematurely. A
      better understanding of factors associated with endocrine therapy initiation and
      persistence could inform practitioners how to support patients. We analyzed data
      from a longitudinal study of 2,268 women diagnosed with breast cancer and
      reported to the Metropolitan Detroit and Los Angeles SEER cancer registries in
      2005-2007. Patients were surveyed approximately both 9 months and 4 years after
      diagnosis. At the 4-year mark, patients were asked if they had initiated
      endocrine therapy, terminated therapy, or were currently taking therapy (defined
      as persistence). Multivariable logistic regression models examined factors
      associated with initiation and persistence. Of the 743 patients eligible for
      endocrine therapy, 80 (10.8 %) never initiated therapy, 112 (15.1 %) started
      therapy but discontinued prematurely, and 551 (74.2 %) continued use at the
      second time point. Compared with whites, Latinas (OR 2.80, 95 % CI 1.08-7.23) and
      black women (OR 3.63, 95 % CI 1.22-10.78) were more likely to initiate therapy.
      Other factors associated with initiation included worry about recurrence (OR
      3.54, 95 % CI 1.31-9.56) and inadequate information about side effects (OR 0.24,
      95 % CI 0.10-0.55). Factors associated with persistence included two or more
      medications taken weekly (OR 4.19, 95 % CI 2.28-7.68) and increased age (OR 0.98,
      95 % CI 0.95-0.99). Enhanced patient education about potential side effects and
      the effectiveness of adjuvant endocrine therapy in improving outcomes may improve
      initiation and persistence rates and optimize breast cancer survival.

PMID- 23542960
TI  - Handling intra-cluster correlation when analyzing the effects of decision support
      on health care process measures.
AB  - The clinical worksite constitutes a naturally clustered environment, posing
      challenges in the statistical analysis of quality improvement interventions such
      as computerized decision support. Ignoring clustering in the analysis may lead to
      biased effect estimates, underestimating the variance and hence type I errors.
      This paper presents a secondary analysis on data from a previously published,
      cluster randomized trial in cardiac rehabilitation. We compared six different
      statistical analysis methods (weighted and unweighted t-test; adjusted chi2 test;
      normal and multilevel logistic regression analysis; and generalized estimation
      equations). There were considerable differences in both point estimates and p
      values derived by the methods, and differences were larger with increasing
      intracluster correlation.

PMID- 23542962
TI  - How Turing and Wolf influenced my Decision Support Systems.
AB  - Decision Support Systems (DSS) have a vital role to play in today's scenario for
      Patient Care. They can embody a vast knowledge not normally found in one
      individual where diagnosis and treatment are involved. This paper highlights the
      training in minute details and precise mathematics needed in a successful DSS and
      indicates how such attention-to-detail was instilled into the writer as a result
      of working with Alan Turing and Emil Wolf who have both since achieved world-wide
      recognition in their own fields as a result of international publicity by the
      current writer. The article discusses four Decision Support Systems written by
      the present writer all of which have been shown to improve patient treatment and
      care, and which are of such complexity that, without their use, patient care
      would fall short of optimum. The Systems considered are those for Intensive Care
      Units, Cardiovascular Surgery, a Programmed Investigation Unit, and Diagnosis of
      Congenital Abnormalities. All these Systems have performed better than the human
      alternatives and have shown their value in the improvement of patient care.

PMID- 23542963
TI  - Designing prognostic models by reinforcing linear separation.
AB  - Variety of prognostic models can be designed on the basis of learning sets by
      using the principle of linear separability. The degree of linear separability of
      two learning sets can be evaluated on the basis of the minimal value of the
      perceptron criterion function, which belongs to a larger family of the convex and
      piecewise linear (CPL) criterion functions. Parameters constituting the minimal
      value of a given CPL criterion function can define particular prognostic model.
      Prognostic models have been designed this way, for example, on the basis of
      genetic data sets.

PMID- 23542964
TI  - Personalized medicine and the need for decision support systems.
AB  - Advances in genomics and human genetics have enabled a more detailed
      understanding of the impact of genetics in a disease and its treatment. In
      addition to a patient's clinical signs and symptoms, physicians can now or in
      near future consider genetic data for their diagnosis and treatment decisions.
      This new information source based on genome and gene expression analysis makes
      clinical decision processes even more complex. Beyond, behavioral and
      environmental aspects should also be considered in order to realize personalized
      medicine. Given these additional information sources, the need for support in
      decision making is increasing. In this paper, we introduce a vision how knowledge
      based systems or decision support systems can help to realize personalized
      medicine and we explore the upcoming challenges for clinical decision support in
      that context.

PMID- 23542965
TI  - Analyzing the "CareGap": assessing gaps in adherence to clinical guidelines in
      adult soft tissue sarcoma.
AB  - Clinical decision support systems (CDSSs) are gaining popularity as tools that
      assist physicians in optimizing medical care. These systems typically comply with
      evidence-based medicine and are designed with input from domain experts.
      Nonetheless, deviations from CDSS recommendations are abundant across a broad
      spectrum of disorders, raising the question as to why this phenomenon exists.
      Here, we analyze this gap in adherence to a clinical guidelines-based CDSS by
      examining the physician treatment decisions for 1329 adult soft tissue sarcoma
      patients in northern Italy using patient-specific parameters. Dubbing this
      analysis "CareGap", we find that deviations correlate strongly with certain
      disease features such as local versus metastatic clinical presentation. We also
      notice that deviations from the guideline-based CDSS suggestions occur more
      frequently for patients with shorter survival time. Such observations can direct
      physicians' attention to distinct patient cohorts that are prone to higher
      deviation levels from clinical practice guidelines. This illustrates the value of
      CareGap analysis in assessing quality of care for subsets of patients within a
      larger pathology.

PMID- 23542966
TI  - A novel way of integrating rule-based knowledge into a web ontology language
      framework.
AB  - Web ontology language (OWL), used in combination with the Protege visual
      interface, is a modern standard for development and maintenance of ontologies and
      a powerful tool for knowledge presentation. In this work, we describe a novel
      possibility to use OWL also for the conceptualization of knowledge presented by a
      set of rules. In this approach, rules are represented as a hierarchy of
      actionable classes with necessary and sufficient conditions defined by the
      description logic formalism. The advantages are that: the set of the rules is not
      an unordered set anymore, the concepts defined in descriptive ontologies can be
      used directly in the bodies of rules, and Protege presents an intuitive tool for
      editing the set of rules. Standard ontology reasoning processes are not
      applicable in this framework, but experiments conducted on the rule sets have
      demonstrated that the reasoning problems can be successfully solved.

PMID- 23542967
TI  - Attitudes and experience of Dutch general practitioners regarding computerized
      clinical decision support.
AB  - Dutch general practices have a high adoption rate for computerized patient
      records and clinical decision support. We sought to measure the attitudes and
      experience of Dutch general practitioners towards clinical decision support.
      METHODS: A preliminary survey was created based on questions from published
      surveys, modified with the results of interviews. The final web-based survey was
      administered to 43 general practitioners in a practice area where a decision
      support implementation is planned. RESULTS: Thirty general practitioners (70%)
      completed the survey. Most felt that decision support is a good idea (23/30),
      although fewer reported positive experience with decision support (10/30).
      Participants were supportive of rules and guidelines, but commonly had the sense
      that there were too many alerts. CONCLUSION: Dutch clinicians are positive about
      decision support, but future efforts should try to reduce the perception of
      overload, for example by ensuring that alerts are relevant and choosing less
      interruptive forms of notification for less severe alerts.

PMID- 23542968
TI  - A comparison of English and French approaches to providing patients access to
      Summary Care Records: scope, consent, cost.
AB  - Online access to records is part of the process of empowering patients. National
      health services in both France and England have introduced systems to provide
      online access to summary health data. The English system was called the "Summary
      Care Record (SCR)," made accessible to patients through "HealthSpace". The French
      system Dossier Medical Personnel (DMP) is a patient controlled record clinicians
      enter data into. The objective was to compare the programmes and lessons from the
      introduction of patient access. We carried out a literature review. The English
      system has been progressively de-scoped, with HealthSpace due to close in 2013,
      only 0.01% of the population signing up for "advanced accounts". The French
      system slowly grows as more documents are added; though only 0.31% of the
      population have opened a DMP. The English SCR has an opt-out consent model,
      whereas the French DMP is patient controlled opt-in consent model. The SCR sits
      within an NHS intranet while the DMP sits on the Internet. Both systems have
      costs of around 200 million Euro. Providing patients online access to their
      medical records is potentially empowering. However, the English HealthSpace and
      SCR have failed to deliver and are due to be withdrawn as methods of providing
      patients online access. The French system is still in operation but much
      criticized for its high costs and low uptake. The design of these systems does
      not appear to have met patients' needs or been readily integrated into physicians
      workflow.

PMID- 23542969
TI  - Global quality indicators for primary care Electronic Patient Records.
AB  - Electronic Patient Records can be interfaced with medical decision support
      systems and quality of care assessment tools. An easy way of measuring the
      quality of EPR data is therefore essential. This study identified a number of
      global quality indicators (tracers) that could be easily calculated and validated
      them by correlating them with the Sensitivity and Positive Predictive Value (PPV)
      of data extracted from the EPR. Sensitivity and PPV of automatically extracted
      data were calculated using a gold standard constructed using answers to questions
      GPs were asked at the end of each contact with a patient. These properties were
      measured for extracted diagnoses, drug prescriptions, and certain parameters.
      Tracers were defined as drug-disease pairs (e.g. insulin-diabetes) with the
      assumption that if the patient is taking the drug, then the patient is suffering
      from the disease. Four tracers were identified that could be used for the
      ResoPrim primary care research database, which includes data from 43 practices,
      10,307 patients, and 13,372 contacts. Moderately positive correlations were found
      between the 4 tracers and between the tracers and the sensitivity of
      automatically extracted diagnoses. For some purposes, these results may support
      the potential use of tracers for monitoring the quality of information systems
      such as EPRs.

PMID- 23542971
TI  - Structured knowledge acquisition for defining guideline-compliant pathways.
AB  - Healthcare providers are facing an enormous cost pressure, wherefore the
      assurance of an efficient care on a high level of quality is of decisive
      importance. Clinical guidelines and clinical pathways have been established for
      that purpose. Clinical guidelines offer abstract recommendations for diagnostic
      and therapeutic issues, while clinical pathways are a road map of patient
      management. The consideration of clinical guidelines during pathway development
      is highly recommended. But the transfer of evident knowledge (clinical
      guidelines) to care processes (clinical pathways) is not straightforward due to
      different information contents and semantical constructs. This article proposes a
      model-driven approach in conjunction with a developed knowledge acquisition tool
      to improve the development of guideline-compliant pathways.

PMID- 23542972
TI  - Tempolenses with variable magnification for sonic representation of medical data.
      Application for cardiac signals.
AB  - The purpose of this study was to develop the tools and the methodology for a
      systematic analysis of usefulness of adding sonic representation of data,
      supplementary to visualization. This paper is mainly dedicated various temporal
      lenses, including the newly developed lenses with variable magnification,
      proposed as a tool for a better perception of short events combined with a
      compression of irrelevant intervals. Sonification procedures are also briefly
      presented. The programs were tested using various cardiac signals: ECG and heart
      rate HR both in humans and in rats (experimental data). The results, represented
      by the sound files, were uploaded in an accessible library, which contains both
      sonic and visual representation of the signals.

PMID- 23542973
TI  - System for selecting relevant information for decision support.
AB  - We implemented a prototype of a decision support system called SIR which has a
      form of a web-based classification service for diagnostic decision support. The
      system has the ability to select the most relevant variables and to learn a
      classification rule, which is guaranteed to be suitable also for high-dimensional
      measurements. The classification system can be useful for clinicians in primary
      care to support their decision-making tasks with relevant information extracted
      from any available clinical study. The implemented prototype was tested on a
      sample of patients in a cardiological study and performs an information
      extraction from a high-dimensional set containing both clinical and gene
      expression data.

PMID- 23542974
TI  - Computational cognitive modeling for the diagnosis of Specific Language
      Impairment.
AB  - Specific Language Impairment (SLI), as many other cognitive deficits, is
      difficult to diagnose given its heterogeneous profile and its overlap with other
      impairments. Existing techniques are based on different criteria using behavioral
      variables on different tasks. In this paper we propose a methodology for the
      diagnosis of SLI that uses computational cognitive modeling in order to capture
      the internal mechanisms of the normal and impaired brain. We show that machine
      learning techniques that use the information of these models perform better than
      those that only use behavioral variables.

PMID- 23542975
TI  - Entropy-driven decision tree building for decision support in gastroenterology.
AB  - Gastroesophageal reflux disease is a serious clinical problem, which can
      significantly impair health-related quality of life, thus having global
      implications for patients. The first step for a doctor is the clinical
      classification of the patients, divided into classes after being subjected to
      endoscopic examinations to control if there are lesions of the esophageal mucosa,
      and if present, the severity of these lesions. 269 patients were taken into
      consideration (4 healthy patients, 219 with non erosive reflux disease, 21 with
      erosive reflux disease, 15 with complicated erosive reflux disease, 10 with
      Barrett's disease). A set of values taken from gastroscopy, ph-metry and
      manometry tests were considered and a decision tree was made to classify every
      patient. Entropy and information gain were calculated for each node to create the
      most possible simple tree. The resulting tree presents some paths including a
      significant number of persons; the values that build these paths can be
      considered characteristic of each class of patient. This method can be a basis to
      develop a diagnostic decision support for a training doctor starting from a set
      of characteristics, specific to a class of patient.

PMID- 23542976
TI  - Sharing and reusing multimedia multilingual educational resources in medicine.
AB  - The paper describes the Eurogene portal for sharing and reusing multilingual
      multimedia educational resources in human genetics. The content is annotated
      using concepts of two ontologies and a topic hierarchy. The ontology annotation
      is used to guide search and for calculating semantically similar content.
      Educational resources can be aggregated into learning packages. The system is in
      routine use since 2009.

PMID- 23542977
TI  - An ontological treatment of clinical prediction rules implementing the Alvarado
      score.
AB  - A lack of acceptance has hindered the widespread adoption and implementation of
      clinical prediction rules (CPRs). The use of clinical decision support systems
      (CDSSs) has been advocated as one way of facilitating a broader dissemination and
      validation of CPRs. This requires computable models of clinical evidence based on
      open standards rather than closed proprietary content. The on-going TRANSFoRm
      project has developed ontological models of CPRs suitable for providing CPR based
      decision support. This paper presents a description of the design and
      implementation of the ontology model for CPRs that has been proposed. The
      conceptual validity of the ontology is discussed using the example of a specific
      CPR in the form of the Alvarado Score for acute appendicitis. We demonstrate how
      the model is used to query the structure of this particular rule, providing a
      computable representation suitable for CPRs in general.

PMID- 23542978
TI  - Simultaneously authoring and modeling clinical practice guidelines: a case study
      in the therapeutic management of type 2 diabetes in France.
AB  - By providing patient-specific advice, clinical decision support systems (CDSSs)
      are expected to promote the implementation of clinical practice guidelines (CPGs)
      to improve the quality of care. However, produced as texts, often incomplete and
      ambiguous, CPGs are difficult to translate into the formal knowledge bases (KBs)
      of CDSSs. The French National Authority for Health (HAS) decided to update CPGs
      on the management of type 2 diabetes. This work illustrates the simultaneous
      development of the text and its formal counterpart in a CDSS named RecosDiab.
      CPGs were elaborated by a working group according to the guideline development
      methodology. Textual recommendations were graded, either as evidence-based when
      evidence existed or as consensus-based when acknowledge by the working group.
      Knowledge modeling was performed following the steps of de-abstraction,
      disambiguation, and verification of completeness. This last step generated
      clinical situations not explicitly mentioned in the text and were graded as
      expert-based. The resulting KB provides therapeutic advice for 805 clinical
      situations, among which 2 are graded as evidence-based, 37 are consensus-based,
      and 766 are expert-based. However, because of the amount of expert-based
      propositions, the HAS did not endorse the system.

PMID- 23542980
TI  - A conceptual framework for automating the operational and strategic decision
      making process in the health care delivery system.
AB  - Making reliable and justified operational and strategic decisions is a really
      challenging task in the health care domain. So far, the decisions have been made
      based on the experience of managers and staff, or they are evaluated with
      traditional methods, using inadequate data. As a result of this kind of decision
      making process, attempts to improve operations usually have failed or led to only
      local improvements. Health care organizations have a lot of operational data, in
      addition to clinical data, which is the key element for making reliable and
      justified decisions. However, it is progressively problematic to access it and
      make usage of it. In this paper we discuss about the possibilities how to exploit
      operational data in the most efficient way in the decision-making process. We'll
      share our future visions and propose a conceptual framework for automating the
      decision-making process.

PMID- 23542981
TI  - Supporting drug prescription through autocompletion.
AB  - Computerized prescription is a central component in modern clinical information
      systems. It allows scheduling drugs delivery, exams and other types of care. It
      is thought to be a useful tool for the reduction of medication errors and for the
      improvement of medication logistics. Whereas the success of the computerized
      prescription depends on the unambiguous selection of the manipulated concepts,
      there is a strong variability between the preferred terms of clinicians of
      different backgrounds. Moreover, users sometimes want to use synonyms or don't
      know the exact spelling of the term. This makes the search for desired procedure
      name through large size vocabularies time-consuming for users. In order to
      facilitate the prescriptions process, we have built a tool that proposes the most
      likely terms based on the first letters inputted by the user. The tool helps
      selecting the most appropriate term by ranking the possible results in a clever
      manner. Experimental evaluation shows promising results and indicates the tool
      ease the terminology manipulations.

PMID- 23542982
TI  - Physicians perceptions of an educational support system integrated into an
      electronic health record.
AB  - The purpose of this study is to determine the perceptions by physicians of an
      educational system integrated into an electronic health record (EHR). Traditional
      approaches to continuous medical education (CME) have not shown improvement in
      patient health care outcomes. Hospital Italiano de Buenos Aires (HIBA) has
      implemented a system that embeds information pearls into the EHR, providing
      learning opportunities that are integrated into the patient care process. This
      study explores the acceptability and general perceptions of the system by
      physicians when they are in the consulting room. We interviewed 12 physicians
      after one or two weeks of using this CME system and we performed a thematic
      analysis of these interviews. The themes that emerged were use and ease of use of
      the system; value physicians gave to the system; educational impact on
      physicians; respect for the individual learning styles; content available in the
      system; and barriers that were present or absent for using the CME system. We
      found that the integrated CME system developed at HIBA was well accepted and
      perceived as useful and easy to use. Future work will involve modifications to
      the system interface, expansion of the content offered and further evaluation.

PMID- 23542983
TI  - Project I-COP - architecture of software tool for decision support in oncology.
AB  - This article briefly describes the development of the I-COP tool, which is
      designed to promote education and decision making of clinical oncologists. It is
      based on real data from medical facilities, which are processed, stored in
      database, analyzed and finally displayed in an interactive software application.
      Used data sources are shortly described in individual sections together with the
      functionality of developed tools. The final goal of this project is to provide
      support for work and education within each involved partner center. Clinical
      oncologists are therefore supposed to be the authors and users at the same time.

PMID- 23542984
TI  - Design and implementation of the standards-based personal intelligent self
      management system (PICS).
AB  - Against the background of demographic change and a diminishing care workforce
      there is a growing need for personalized decision support. The aim of this paper
      is to describe the design and implementation of the standards-based personal
      intelligent care systems (PICS). PICS makes consistent use of internationally
      accepted standards such as the Health Level 7 (HL7) Arden syntax for the
      representation of the decision logic, HL7 Clinical Document Architecture for
      information representation and is based on a open-source service-oriented
      architecture framework and a business process management system. Its
      functionality is exemplified for the application scenario of a patient suffering
      from congestive heart failure. Several vital signs sensors provide data for the
      decision support system, and a number of flexible communication channels are
      available for interaction with patient or caregiver. PICS is a standards-based,
      open and flexible system enabling personalized decision support. Further
      development will include the implementation of components on small computers and
      sensor nodes.

PMID- 23542985
TI  - Prognostic decision support using symbolic dynamics in CTG monitoring.
AB  - Foetal heart rate variability is one of the most important parameters to monitor
      foetal wellbeing. Linear parameters, widely employed to study foetal heart
      variability, have shown some limitations in highlight dynamics potentially
      relevant. During the last decades, therefore, nonlinear analysis methods have
      gained a growing interest to analyze the chaotic nature of cardiac activity.
      Parameters derived by techniques investigating nonlinear can be included in
      computerised systems of cardiotocographic monitoring. In this work, we described
      an application of symbolic dynamics to analyze foetal heart rate variability in
      healthy foetuses and a concise index, introduced for its classification in
      antepartum CTG monitoring. The introduced index demonstrated to be capable to
      highlight differences in heart rate variability and resulted correlated with the
      Apgar score at birth, in particular, higher variability indexes values are
      associated to early greater vitality at birth. These preliminary results confirm
      that SD can be a helpful tool in CTG monitoring, supporting medical decisions in
      order to assure the maximum well-being of newborns.

PMID- 23542986
TI  - Rule-based healthcare-associated bloodstream infection classification and
      surveillance system.
AB  - Healthcare-associated infections (HAIs) are a major patient safety issue. These
      adverse events add to the burden of resource use, promote resistance to
      antibiotics, and contribute to patient deaths and disability. A rule-based HAI
      classification and surveillance system was developed for automatic integration,
      analysis, and interpretation of HAIs and related pathogens. Rule-based
      classification system was design and implement to facilitate healthcare
      associated bloodstream infection (HABSI) surveillance. Electronic medical records
      from a 2200-bed teaching hospital in Taiwan were classified according to
      predefined criteria of HABSI. The detailed information in each HABSI was
      presented systematically to support infection control personnel decision. The
      accuracy of HABSI classification was 0.94, and the square of the sample
      correlation coefficient was 0.99.

PMID- 23542987
TI  - Diagnostic decision support of heart rate turbulence in sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is characterized by repeated upper-airway
      obstruction during sleep. It is diagnosed by polysomnographic studies, scoring
      OSAS severity by an apneas/hypopneas index associated to worse prognosis, mainly
      for an increased cardiovascular morbidity. Cardiac autonomic impairments involved
      in the development of cardiovascular disease in OSAS can be assessed by heart
      rate turbulence (HRT) analysis and aim of the paper is to show the increased
      medical decision support by HRT evaluation in OSAS patients. HRT has been
      assessed in 274 polysomnographic recordings of mild-to-severe OSAS patients and
      an overall cardiorespiratory risk scoring (CRRIS) index has been proposed on the
      base of both OSAS severity and HRT assessment. Results showed that, while the
      only polysomnografic analysis would have equally ranked OSAS patients within
      their mild-to-severe classification, CRRIS index allows to identify a 19% of
      severe-OSAS patients at very high risk of sudden cardiac death, a 13% of moderate
      OSAS patients with a risk level comparable to those of severe, and a 17% of mild
      OSAS patients with evidence of an autonomic impairment. CRRIS index, detecting
      patients at greater probability of worsening could give to the physician a very
      useful medical decision support in the follow up of this particular chronic
      disease.

PMID- 23542988
TI  - Utilization of ontology look-up services in information retrieval for biomedical
      literature.
AB  - With the vast amount of biomedical data we face the necessity to improve
      information retrieval processes in biomedical domain. The use of biomedical
      ontologies facilitated the combination of various data sources (e.g. scientific
      literature, clinical data repository) by increasing the quality of information
      retrieval and reducing the maintenance efforts. In this context, we developed
      Ontology Look-up services (OLS), based on NEWT and MeSH vocabularies. Our
      services were involved in some information retrieval tasks such as gene/disease
      normalization. The implementation of OLS services significantly accelerated the
      extraction of particular biomedical facts by structuring and enriching the data
      context. The results of precision in normalization tasks were boosted on about
      20%.

PMID- 23542989
TI  - A proposed novel method for CHD screening by fetal heart murmur detection using
      phonocardiography.
AB  - The paper presents a novel screening method to indicate congenital heart diseases
      (CHD) which otherwise would remain undetected because of their low level.
      Therefore, not belonging to the high-risk population, they are omitted from the
      regular fetal monitoring with ultrasound echocardiography. Based on the fact that
      CHDs are morphological defects of the heart causing turbulent blood flow, this
      turbulence appears as a murmur, which can be detected by phonocardiography (PCG).
      The proposed method applies measurements on the maternal abdomen and from the
      recorded sound signal a sophisticated processing determines the fetal heart
      murmur. The paper describes the problems and the additional advantages of the PCG
      method including the possibility of measurements at home and its combination with
      the prescribed regular cardiotocographic (CTG) monitoring. The proposed screening
      process implemented on a telemedicine system provides an enhanced safety against
      hidden cardiac diseases.

PMID- 23542990
TI  - DIOS - database of formalized chemotherapeutic regimens.
AB  - Chemotherapeutic regimens (CHR) and their administration are routine practice in
      contemporary oncology. The development of a structured, electronic database of
      standard CHR can help the faster propagation of information about new CHR and at
      the same time enable assessment of their adherence in clinical practice. The goal
      was to develop a standardized way to describe a regimen using XML, fill the
      database with currently available regimens and develop tools to assess the
      adherence of the treatment to chosen regimen, compare the dose-intensity and
      recognize the regimen from existing data on drug administration. The data are
      being inserted in cooperation with expert oncologists and the database currently
      contains about 260 CHRs. Such system can be used to enhance decision support
      systems and interoperability of HIS. The database and tools are available online
      on the internet.

PMID- 23542991
TI  - Adverse drug event prevention in neonatal care: a rule-based approach.
AB  - Adverse drug events (ADE) in a neonatal unit can be of great importance due to
      the underlying nature and the special characteristics of the patients. This paper
      presents our work on the development of a knowledge base (KB) for supporting the
      identification and prevention of ADEs. First, a literature review was conducted
      to identify ADEs observed through the use of the most commonly-used drugs in a
      specific neonatal unit. Then, the acquired knowledge was encoded according to an
      ontological data model developed for the representation of the specific facts for
      the neonatal unit. Finally, a rule-based prototype consisting of 164 rules was
      implemented in order to represent and simulate the inference procedure about
      preventing ADEs.

PMID- 23542993
TI  - Interoperability evaluation case study: an Obstetrics-Gynecology Department and
      related Information Systems.
AB  - The paper presents the steps and metrics for evaluating the interoperability of
      an Obstetrics-Gynecology Department Information System applied on Bega Clinic
      Timisoara regarding its readiness for interoperability in relation with similar
      systems. The developed OGD IS was modeled starting from the Generic Component
      Model and sends information to other medical units using the HL7 Clinical
      Document Architecture and Continuity of Care Document standards. The data for
      evaluation are real, collected between 2009 and 2010 from Bega Clinic Timisoara.
      The results were relatively good for the investigated data and structure.

PMID- 23542994
TI  - Interest propagation for knowledge extraction and representation.
AB  - Due to the increasing number of available biomedical data repositories, providing
      a comprehensive and intuitive access to information is still a demanding task for
      Information Retrieval systems. In this work we present an interactive data
      exploration system that retrieves relevant information by propagating the user's
      interest within a network. The developed techniques have been applied to two
      different retrieval tasks useful for biomedical research: the prioritization of
      proteins related to a disease of interest and the search of publications in the
      literature. The method relies on a network of biomedical entities, scoring of
      entities of interest by the user, and score propagation. The assessment of the
      relevance of the retrieved information confirmed a high accuracy of the presented
      algorithms for both the domains considered.

PMID- 23542995
TI  - Automatic system testing of a decision support system for insulin dosing using
      Google Android.
AB  - Hyperglycaemia in hospitalized patients is a common and costly health care
      problem. The GlucoTab system is a mobile workflow and decision support system,
      aiming to facilitate efficient and safe glycemic control of non-critically ill
      patients. Being a medical device, the GlucoTab requires extensive and
      reproducible testing. A framework for high-volume, reproducible and automated
      system testing of the GlucoTab system was set up applying several Open Source
      tools for test automation and system time handling. The REACTION insulin
      titration protocol was investigated in a paper-based clinical trial (PBCT). In
      order to validate the GlucoTab system, data from this trial was used for
      simulation and system tests. In total, 1190 decision support action points were
      identified and simulated. Four data points (0.3%) resulted in a GlucoTab system
      error caused by a defective implementation. In 144 data points (12.1%),
      calculation errors of physicians and nurses in the PBCT were detected. The test
      framework was able to verify manual calculation of insulin doses and detect
      relatively many user errors and workflow anomalies in the PBCT data. This shows
      the high potential of the electronic decision support application to improve
      safety of implementation of an insulin titration protocol and workflow management
      system in clinical wards.

PMID- 23542997
TI  - Implementing healthcare information security: standards can help.
AB  - Using widely spread common approaches to systems security in health dedicated
      controlled environments, a level of awareness, confidence and acceptance of
      relevant standardisation is evaluated. Patients' information is sensitive, so
      putting appropriate organisational techniques as well as modern technology in
      place to secure health information is of paramount importance. Mobile devices are
      becoming the top priorities in advanced information security planning with
      healthcare environments being no exception. There are less and less application
      areas in healthcare without having a need for a mobile functionality which
      represents an even greater information security challenge. This is also true in
      emergency treatments, rehabilitation and homecare just to mention a few areas
      outside hospital controlled environments. Unfortunately quite often traditional
      unsecured communications principles are still in routine use for communicating
      sensitive health related information. The security awareness level with users,
      patients and care professionals is not high enough so potential threats and risks
      may not be addressed and the respective information security management is
      therefore weak. Standards like ISO/IEC 27000 ISMS family, the ISO/IEC 27799
      information security guidelines in health are often not well known, but together
      with legislation principles such as HIPAA, they can help.

PMID- 23542998
TI  - Comparing the use of SNOMED CT and ICD10 for coding clinical conditions to
      implement laboratory guidelines.
AB  - Laboratory medicine is responsible for an important part of hospital expenditure.
      Providing appropriate decision support to laboratory test requesters at the point
      of care is one of the main incentives for implementing laboratory guidelines,
      which can improve medical care. Laboratory guidelines developed by local experts
      in the Parisian region and two national guidelines for dyslipidemia were analyzed
      to extract test ordering recommendations. Clinical conditions which can be a
      trigger to order or not to order laboratory tests were extracted and mapped with
      ICD10 and SNOMED CT: 43.1% of clinical conditions were matched by ICD10 whereas
      SNOMED CT covered 80.1% of these conditions. For the non-mapped conditions, the
      main problem was found to be the ambiguity of the terms used in the guidelines.
      Ordinal characteristics of some clinical conditions and using terms more specific
      than SNOMED CT were other causes of mapping failure. Applying consistent and
      explicit concepts in the development of guidelines would lead to better
      implementation. By resolving the guideline ambiguity, SNOMED CT is a good choice
      and covers almost all of the clinical conditions in laboratory guidelines which
      are needed to implement in a Clinical Decision Support System.

PMID- 23543002
TI  - Enterococcus faecalis infective endocarditis: a pilot study of the relationship
      between duration of gentamicin treatment and outcome.
AB  - BACKGROUND: Because of the nephrotoxic effects of aminoglycosides, the Danish
      guidelines on infective endocarditis were changed in January 2007, reducing
      gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to
      only 2 weeks. In this pilot study, we compare outcomes in patients with
      Enterococcus faecalis infective endocarditis treated in the years before and
      after endorsement of these new recommendations. METHODS AND RESULTS: A total of
      84 consecutive patients admitted with definite left-sided E faecalis endocarditis
      in the period of 2002 to 2011 were enrolled. Forty-one patients were treated
      before and 43 patients were treated after January 1, 2007. There were no
      significant differences in baseline characteristics. At hospitalization, the 2
      groups had similar estimated glomerular filtration rates of 66 and 75 mL/min
      (P=0.22). Patients treated before January 2007 received gentamicin for a
      significantly longer period (28 versus 14 days; P<0.001). The primary outcome, 1
      year event-free survival, did not differ: 66% versus 69%, respectively (P=0.75).
      At discharge, the patients treated before 2007 had a lower estimated glomerular
      filtration rate (45 versus 66 mL/min; P=0.008) and a significantly greater
      decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min;
      P=0.009) compared with those treated after 2007. CONCLUSIONS: Our present pilot
      study suggests that the recommended 2-week treatment with gentamicin seems
      adequate and preferable in treating non-high-level aminoglycoside-resistant E
      faecalis infective endocarditis. The longer duration of gentamicin treatment is
      associated with worse renal function. Although the certainty of the clinical
      outcomes is limited by the sample size, outcomes appear to be no worse with the
      shorter treatment duration. Randomized, controlled studies are warranted to
      substantiate these results.

PMID- 23543003
TI  - A new era for treating Enterococcus faecalis endocarditis: ampicillin plus short
      course gentamicin or ampicillin plus ceftriaxone: that is the question!

PMID- 23543004
TI  - Outcomes after acute myocardial infarction in HIV-infected patients: analysis of
      data from a French nationwide hospital medical information database.
AB  - BACKGROUND: We aimed to assess in-hospital case fatality and 1-year prognosis in
      HIV-infected patients with acute myocardial infarction. METHODS AND RESULTS: From
      the PMSI (Program de Medicalisation des Systemes d'informatique) database, data
      from 277 303 consecutive acute myocardial infarction patients hospitalized from
      January 1, 2005, to December 31, 2009, were analyzed. Surviving patients were
      followed up for 1 year after discharge. HIV-infected patients were compared with
      uninfected patients. Among the cohort, HIV-infected patients (n=608) accounted
      for 0.22%. All-cause hospital and 1-year mortality rates were lower in the HIV
      infected group than in uninfected patients (3.1% versus 8.1% [P<0.001] and 1.4%
      versus 5.5% [P<0.001], respectively). From the database, we then analyzed a
      cohort derived from a matching procedure, with 1 HIV patient matched with 2
      patients without HIV, based on age and sex (n=1824). Ischemic cardiomyopathy was
      more frequent in the HIV group (7.6% versus 4.2%, P=0.003). Hospitalization and 1
      year mortality rates were similar in the 2 groups (3.1% versus 2.1% [P=0.168] and
      1.4% versus 1.7% [P=0.642], respectively). However, at 12 months,
      hospitalizations for episodes of heart failure were significantly more frequent
      in HIV-infected than in uninfected patients (3.3% versus 1.4%, respectively;
      P=0.020). HIV infection, diabetes mellitus, history of ischemic cardiomyopathy,
      and undergoing percutaneous coronary intervention were associated in univariate
      analysis with occurrence of heart failure. By multivariable analysis, HIV
      infection (odds ratio 2.82, 95% confidence interval 1.32-6.01), diabetes
      mellitus, and undergoing percutaneous coronary intervention remained independent
      predictors of heart failure. CONCLUSIONS: The present study demonstrates that
      after acute myocardial infarction, HIV status influences long-term risk, although
      the short-term risk in HIV patients is comparable to that in uninfected patients.

PMID- 23543005
TI  - Incidence of medium-chain acyl-CoA dehydrogenase deficiency in Canada using the
      Canadian Paediatric Surveillance Program: Role of newborn screening.
AB  - BACKGROUND: The incidence of medium-chain acyl-CoA dehydrogenase deficiency
      (MCADD) was estimated using the Canadian Paediatric Surveillance Program (CPSP)
      in Canada over a three-year period. Data regarding mutations associated with
      MCADD cases were collected wherever available. METHODS: Data were collected over
      a 36-month period using a monthly mailed questionnaire distributed through the
      CPSP to more than 2500 Canadian paediatricians, medical geneticists and
      paediatric pathologists. RESULTS AND CONCLUSIONS: During the three years of MCADD
      surveillance, 46 confirmed cases out of a total of 71 reported cases were found -
      an average of approximately 15 cases per year. This rate is lower than the
      initial estimate of approximately 30 cases per year of MCADD in Canada, based on
      the reported incidence of MCADD in the literature of approximately one in 10,000
      to one in 20,000. All cases ascertained by newborn screening were asymptomatic.
      There were two deaths, both in jurisdictions without newborn screening for MCADD.
      The data support population-based newborn screening for MCADD.

PMID- 23543006
TI  - Are bisphosphonates an indispensable tool in the era of targeted therapy for
      renal cell carcinoma and bone metastases?
AB  - One third of patients with metastatic renal cell carcinoma (RCC) suffer from bone
      metastases. Skeletal involvement in RCC is associated with the occurrence of
      skeletal-related events, and may negatively impact on the outcome of patients
      treated with systemic therapies. In patients with RCC and bone metastases,
      therapies that inhibit osteoclasts, as bisphosphonates and denosumab, are used as
      adjunct to systemic targeted therapies to prevent skeletal-related events. Data
      suggest that they may also improve the outcome of systemic targeted therapies.
      Herein we review the preclinical and clinical data on their use, as well as
      remaining open questions. 

PMID- 23543007
TI  - Can observations of workplace bullying really make you depressed? A response to
      Emdad et al.
AB  - BACKGROUND: A recent study by Emdad and colleagues published in International
      Archives of Occupational and Environmental Health concluded that being a
      bystander to workplace bullying is related to future symptoms of depression. In
      this response to the authors, we argue, through the use of empirical evidence,
      that this relationship can be explained by the observers own exposure to
      bullying. Furthermore, by also investigating the reversed association between the
      variables, we show that observations of workplace bullying can be influenced by
      symptoms of psychological distress. METHOD: A reanalysis of prospective
      questionnaire survey data with a two-year time lag based on a representative
      sample of Norwegian employees was used to determine long-term relationships
      between observed bullying, self-reported exposure to bullying, and psychological
      distress. RESULTS: Bivariate, baseline observations of others being bullied were
      significantly associated with subsequent symptoms of psychological distress. Yet,
      this association disappeared when controlling for the observers own exposure to
      bullying. Analyzing reversed relationship between the variables, baseline
      symptoms of distress predicted being a bystander at follow-up. CONCLUSION: By
      showing that the relationship between being a bystander to bullying and distress
      can be fully explained by the observers own exposure to bullying, our results
      question the conclusion by Emdad et al. (Int Arch Occup Environ Health. doi:
      10.1007/s00420-012-0813-1 , 2012) that observed bullying in itself is related to
      subsequent distress. Together with the finding that psychological distress
      predicts subsequent observations of bullying, it is concluded that future
      research on observers should always take the observers' own exposure to bullying,
      as well as negative perceptions biases, into account.

PMID- 23543008
TI  - Comment on "can observations of workplace bullying really make you depressed? A
      response to Emdad et al. 2013" by Nielsen and Einarsen.

PMID- 23543009
TI  - Oxidative stress: the mitochondria-dependent and mitochondria-independent
      pathways of apoptosis.
AB  - Oxidative stress basically defines a condition in which prooxidant-antioxidant
      balance in the cell is disturbed; cellular biomolecules undergo severe oxidative
      damage, ultimately compromising cells viability. In recent years, a number of
      studies have shown that oxidative stress could cause cellular apoptosis via both
      the mitochondria-dependent and mitochondria-independent pathways. Since these
      pathways are directly related to the survival or death of various cell types in
      normal as well as pathophysiological situations, a clear picture of these
      pathways for various active molecules in their biological functions would help
      designing novel therapeutic strategy. This review highlights the basic mechanisms
      of ROS production and their sites of formation; detail mechanism of both
      mitochondria-dependent and mitochondria-independent pathways of apoptosis as well
      as their regulation by ROS. Emphasis has been given on the redox-sensitive ASK1
      signalosome and its downstream JNK pathway. This review also describes the
      involvement of oxidative stress under various environmental toxin- and drug
      induced organ pathophysiology and diabetes-mediated apoptosis. We believe that
      this review would provide useful information about the most recent progress in
      understanding the mechanism of oxidative stress-mediated regulation of apoptotic
      pathways. It will also help to figure out the complex cross-talks between these
      pathways and their modulations by oxidative stress. The literature will also shed
      a light on the blind alleys of this field to be explored. Finally, readers would
      know about the ROS-regulated and apoptosis-mediated organ pathophysiology which
      might help to find their probable remedies in future.

PMID- 23543010
TI  - Induction of Dectin-1 and asthma-associated signal transduction pathways in RAW
      264.7 cells by a triple-helical (1, 3)-beta-D glucan, curdlan.
AB  - People living in damp buildings are typically exposed to spore and mycelial
      fragments of the fungi that grow on damp building materials. There is
      experimental evidence that this exposure to triple-helical (1, 3)-beta-D glucan
      and low molecular weight toxins may be associated with non-atopic asthma observed
      in damp and moldy buildings. However, the mechanisms underlying this response are
      only partially resolved. Using the pure (1, 3)-beta-D glucan, curdlan, and the
      murine macrophage cell line, RAW 264.7, there were two objectives of this study.
      The first was to determine whether signal transduction pathways activating asthma
      associated cell signaling pathways were stimulated using mouse transduction
      Pathway Finder((r)) arrays and quantitative real-time (QRT) PCR. The second
      objective was to evaluate the dose and temporal responses associated with
      transcriptional changes in asthma-associated cytokines, the signal transduction
      receptor gene Dectin-1, and various transcription factor genes related to the
      induction of asthma using customized RT-PCR-based arrays. Compared to controls,
      the 10(-7) M curdlan treatment induced significant changes in gene transcription
      predominately in the NFkB, TGF-beta, p53, JAK/STAT, P13/AKT, phospholipase C, and
      stress signaling pathways. The 10(-8) M curdlan treatment mainly induced NFkB and
      TGF-beta pathways. Compared to controls, curdlan exposures also induced
      significant dose- and time-dependent changes in the gene translations. We found
      that that curdlan as a non-allergenic potentiator modulates a network of
      transduction signaling pathways not only associated with TH-1, TH-2, and TH-3
      cell responses including asthma potentiation, but a variety of other cell
      responses in RAW 264.7 cells. These results help provide mechanistic basis for
      some of the phenotypic changes associated with asthma that have been observed in
      in vitro, in vivo, and human studies and open up a hypothesis-building process
      that could explain the rise of non-atopic asthma associated with fungi.

PMID- 23543011
TI  - Zebrafish embryos as an alternative model for screening of drug-induced organ
      toxicity.

PMID- 23543012
TI  - In vitro characterisation of the anti-intravasative properties of the marine
      product heteronemin.
AB  - Metastases destroy the function of infested organs and are the main reason of
      cancer-related mortality. Heteronemin, a natural product derived from a marine
      sponge, was tested in vitro regarding its properties to prevent tumour cell
      intravasation through the lymph-endothelial barrier. In three-dimensional (3D)
      cell cultures consisting of MCF-7 breast cancer cell spheroids that were placed
      on lymph-endothelial cell (LEC) monolayers, tumour cell spheroids induce
      "circular chemorepellent-induced defects" (CCIDs) in the LEC monolayer; 12(S)
      Hydroxyeicosatetraenoic acid (12(S)-HETE) and NF-kappaB activity are major
      factors inducing CCIDs, which are entry gates for tumour emboli intravasating the
      vasculature. This 3D co-culture is a validated model for the investigation of
      intravasation mechanisms and of drugs preventing CCID formation and hence lymph
      node metastasis. Furthermore, Western blot analyses, NF-kappaB reporter, EROD,
      SELE, 12(S)-HETE, and adhesion assays were performed to investigate the
      properties of heteronemin. Five micromolar heteronemin inhibited the directional
      movement of LECs and, therefore, the formation of CCIDs, which were induced by
      MCF-7 spheroids. Furthermore, heteronemin reduced the adhesion of MCF-7 cells to
      LECs and suppressed 12(S)-HETE-induced expression of the EMT marker paxillin,
      which is a regulator of directional cell migration. The activity of CYP1A1, which
      contributed to CCID formation, was also inhibited by heteronemin. Hence,
      heteronemin inhibits important mechanisms contributing to tumour intravasation in
      vitro and should be tested in vivo.

PMID- 23543013
TI  - Global and MGMT promoter hypomethylation independently associated with genomic
      instability of lymphocytes in subjects exposed to high-dose polycyclic aromatic
      hydrocarbon.
AB  - Global hypomethylation, gene-specific methylation, and genome instability are
      common events in tumorigenesis. To date, few studies have examined the aberrant
      DNA methylation patterns in coke oven workers, who are highly at risk of lung
      cancer by occupational exposure to polycyclic aromatic hydrocarbons (PAHs). We
      recruited 82 PAH-exposed workers and 62 unexposed controls, assessed exposure
      levels by urinary 1-hydroxypyrene, and measured genetic damages by comet assay,
      bleomycin sensitivity, and micronucleus assay. The PAHs in coke oven emissions
      (COE) were estimated based on toxic equivalency factors. We used bisulfite-PCR
      pyrosequencing to quantitate DNA methylation in long interspersed nuclear element
      1 (LINE-1) and O(6)-methylguanine-DNA methyltransferase (MGMT). Further, the
      methylation alteration was also investigated in COE-treated human bronchial
      epithelial (16HBE) cells. We found there are higher levels of PAHs in COE. Among
      PAH-exposed workers, LINE-1 and MGMT methylation levels (with CpG site
      specificity) were significantly lowered. LINE-1, MGMT, and its hot CpG site
      specific methylation were negatively correlated with urinary 1-hydroxypyrene
      levels (r = -0.329, p < 0.001; r = -0.164, p = 0.049 and r = -0.176, p = 0.034,
      respectively). In addition, LINE-1 methylation was inversely associated with
      comet tail moment and micronucleus frequency, and a significant increase of
      micronucleus in low MGMT methylation group. In vitro study revealed that
      treatment of COE in 16HBE cells resulted in higher production of BPDE-DNA
      adducts, LINE-1 hypomethylation, hypomethylation, and suppression of MGMT
      expression. These findings suggest hypomethylation of LINE-1 and MGMT promoter
      could be used as markers for PAHs exposure and merit further investigation.

PMID- 23543014
TI  - Commentary to Gebel 2012: a quantitative review should apply meta-analytical
      methods.
AB  - Gebel (2012) performed a quantitative review of inhalation rat studies on the
      association of granular biopersistent dust exposures and lung cancer risk. The
      analytical methods applied are unreliable because they do not fulfil the
      requirements of current meta-analytical methods.

PMID- 23543015
TI  - What does it take to sustain livable public housing communities?

PMID- 23543016
TI  - HUD's Livable Communities Conference: building capacity for change through
      evidence dissemination and partnership-based training.
AB  - BACKGROUND: A growing prioritization for addressing the health needs of low
      resource individuals in public housing has resulted from increased recognition of
      disparities and the effects of housing and the built environment on residents'
      health. With scarce financial resources, creating capacity for local partnerships
      to plan and implement small-scale, evidence-based improvements may be more
      sustainable. The "Livable Communities Conference" held in Philadelphia in 2011 is
      one example of a capacity-building event. OBJECTIVES: The goals of the event were
      to engage local housing authority staff, residents, and service providers in
      education and planning around health disparities issues in public housing by
      presenting evidence of effective practices, creating networking opportunities for
      developing strategic partnerships, and training to foster action planning for
      strategic local initiatives. METHODS: The 2-day conference included one day of
      scientific and practice-based presentations and one day of professionally
      facilitated workshop activities including small and larger group discussions.
      CONCLUSIONS: The event successfully convened wide-ranging stakeholders and
      exposed participants to "bigger picture" views, and was successful in
      disseminating best practices information from research and practice perspectives.
      Wider recruiting for participation and improved integration of Day 1 and Day 2
      activities and participants could have yielded even further impact. Based on the
      success and the perceived potential impact of this event, facilitating similar
      community capacity-building events that convene a wide range of stakeholders to
      discuss health in public housing and low-resource communities is recommended.
      Discussions around the personal dynamics of partnerships and resistance to change
      also proved useful.

PMID- 23543019
TI  - Impact of LEED-certified affordable housing on asthma in the South Bronx.
AB  - BACKGROUND: Green housing reduces energy costs and may mitigate indoor allergens
      and pollutants, improving asthma morbidity. High asthma burden is seen in low
      income neighborhoods. Past studies show improvements in respiratory symptoms when
      living in green homes. OBJECTIVE: Develop partnership with Blue Sea Development
      Company to determine impacts of living in Melrose Commons V (MCV), a Leadership
      in Energy and Environmental Design (LEED) Platinum-certified affordable housing
      complex, on asthma in the South Bronx. METHODS: Participants completed a home
      based respiratory health questionnaire before moving into MCV. Follow-up occurred
      at 6, 12, and 18 months post-move. A home-based educational module was delivered
      on indoor environmental interventions to avoid asthma triggers. A pretest was
      given before the module and a posttest was given 9 months later, including an
      evaluation of behavioral practice changes. RESULTS: Outcomes included decreases
      in continuous daily respiratory symptoms (p < .001), asthma symptoms disrupting
      sleep in the past month (p = .028), and urgent visits to a healthcare
      professional for asthma in the past 3 months (p = .038). Clinically relevant
      outcomes included fewer days with asthma symptoms; asthma episodes; days of work,
      school, or daycare missed; and emergency department visits. Education changes
      from pretest to posttest included increased knowledge about dust mites, roaches,
      mold, and chemical irritants (p = .007). Common behavioral changes included using
      hypoallergenic mattress covers, using green cleaning products, and eliminating
      bedroom carpets. CONCLUSIONS: Findings support the beneficial effect of LEED
      Platinum-certified buildings on respiratory health. Trends may be clinically and
      economically relevant. Advocacy efforts should promote the expansion of green
      housing and emphasize the development of healthy communities.

PMID- 23543020
TI  - What do public housing residents say about their health?
AB  - BACKGROUND: Residents of public housing have poorer health indicators than
      comparably resourced individuals from the larger community. OBJECTIVES: To
      identify major health concerns, issues, and barriers to health of community
      members living in public housing developments, especially as related to
      cardiovascular disease prevention. To identify similarities and differences
      between data collected using two methods to inform future health promotion
      programs and policies. METHODS: Key informant interviews were conducted with
      resident leaders and analyzed qualitatively in eight housing developments.
      Results were compared with quantitative data collected from a resident health
      survey with a large sample that analyzed individual and development-level
      characteristics, major health concerns, and barriers. RESULTS: Several
      development-level characteristics were significantly associated with residents'
      health concerns and barriers, including development size, percentage of Spanish
      speakers, and presence of a tenant task force (TTF); important health promotion
      barriers included lack of resident engagement, inconsistency in programming, lack
      of knowledge of actions to prevent chronic disease, and lack of resources for
      health promotion. Safety-related health concerns were named as a priority.
      CONCLUSIONS: Multiple data collection methods can yield important data about
      community health priorities and barriers; areas of difference and similarity
      between methods are especially useful in guiding health promotion efforts and
      opportunities.

PMID- 23543021
TI  - In-home air filtration for improving cardiovascular health: lessons from a CBPR
      study in public housing.
AB  - BACKGROUND: Particulate air pollution, including from motor vehicles, is
      associated with cardiovascular disease. OBJECTIVES: To describe lessons learned
      from installing air filtration units in public housing apartments next to a major
      highway. METHODS: We reviewed experience with recruitment, retention, and
      acceptance of the air filtration units. RESULTS: Recruitment and retention have
      been challenging, but similar to other studies in public housing. Equipment noise
      and overheated apartments during hot weather have been notable complaints from
      participants. In addition, we found that families with members with Alzheimer's
      or mental disability were less able to tolerate the equipment. CONCLUSIONS: For
      this research, the primary lesson is that working closely with each participant
      is important. A future public health program would need to address issues of
      noise and heat to make the intervention more acceptable to residents.

PMID- 23543022
TI  - Be active together: supporting physical activity in public housing communities
      through women-only programs.
AB  - BACKGROUND: Low-income and minority groups in the United States have low levels
      of physical activity that contribute to health inequities. In public housing
      communities, both built and social environments are key factors that impact
      residents' physical activity levels. OBJECTIVE: To develop and evaluate women
      only physical activity programs that provide women from cultures in which
      physical activity in mixed-gender settings is not acceptable (e.g., Muslim women)
      with physical activity opportunities. METHODS: We describe the use of community
      based participatory research (CBPR) process and evaluation feedback from our
      initial research and evaluation phases, including focus groups, to shape
      interventions. LESSONS LEARNED: Active community engagement in all phases of
      research, including cultural tailoring of interventions, and decisions about
      location and affordability, was critical. Implementing interventions in public
      housing is feasible, but requires frequent feedback from residents and
      correction. CONCLUSIONS: The use of CBPR resulted in the implementation of a
      successful, culturally appropriate set of physical activity interventions,
      specifically for Muslim Somali women. Housing authorities should consider
      incorporating recreational facilities on site and women-only opportunities to
      provide venues for physical activity.

PMID- 23543023
TI  - Addressing chronic disease within supportive housing programs.
AB  - BACKGROUND: Tenants of supportive housing have a high burden of chronic health
      conditions. OBJECTIVES: To examine the feasibility of developing a tenant
      involved health promotion initiative within a "housing first" agency using a
      community-based participatory research (CBPR) framework. METHODS: Qualitative
      analyses of nine research capacity-building group meetings and fifteen individual
      pre- and post-interviews with those who completed a chronic disease self
      management program, resulting in the development of several themes. RESULTS:
      Tenants of supportive housing successfully partnered with health care providers
      to implement a chronic disease self-management program, noting that "health care
      becomes 'relevant' with housing." CONCLUSIONS: Supportive housing organizations
      are well-situated to implement health promotion initiatives. Such publicly
      subsidized housing that is accompanied by comprehensive supports must also
      include self-management training to help people overcome both internal and
      external barriers to addressing chronic health needs.

PMID- 23543024
TI  - Organizing for healthy communities: a report from public housing in Los Angeles.
AB  - BACKGROUND: Public health outcomes in public housing communities deserve and
      require more attention. Recent work in Los Angeles demonstrates a model for
      contributing to improved health outcomes in public housing communities.
      OBJECTIVES: This article describes community organizing and coalition-building
      efforts focused on community health issues in public housing, and documents
      outcomes and lessons learned from resident-led work in the Los Angeles Human
      Right to Housing Collective. METHODS: Our team used a case study of the practice
      of community organizing, coalition building, resident engagement, advocacy,
      health impact assessment, and a human rights framework. RESULTS: Results include
      successes that promote individual and community health in public housing
      communities in Los Angeles, including public housing preservation, improved
      maintenance procedures, and increased tenant participation. CONCLUSIONS:
      Community organizing and resident-driven projects are fundamental to improving
      community health in public housing communities; it is necessary for decision
      makers to deeply engage with organized residents and incorporate their
      recommendations.

PMID- 23543026
TI  - Improving health services for residents through community-based participatory
      research: a public housing leadership perspective.
AB  - BACKGROUND: In response to feedback from a health forum, resident leaders of
      public housing in Washington, DC, were inspired to create a health survey for and
      by the residents. OBJECTIVE: The survey was designed to document residents'
      concerns about health, health care, and environmental threats. It also explored
      tobacco use and support for smoke-free housing. METHODS: A newly created Health
      Planning Committee of the Citywide Advisory Board, including residents,
      academics, and representatives of health and housing organizations, facilitated
      the creation of a health needs assessment. Questionnaires were initially mailed,
      then hand-delivered to every public housing household. More than 1,000 completed
      questionnaires have now been returned. LESSONS LEARNED: This project highlights a
      model that places resident leaders in charge of health issues, including leading
      advocacy efforts for policies to reduce health disparities in public housing. It
      identifies research challenges and ways to overcome them and empowers the
      community for continued research.

PMID- 23543027
TI  - Ecocity mapping using GIS: introducing a planning method for assessing and
      improving neighborhood vitality.
AB  - BACKGROUND: Assessing neighborhood vitality is important to understanding how to
      improve quality of life and health outcomes. The ecocity model recognizes that
      cities are part of natural systems and favors walkable neighborhoods. This
      article introduces ecocity mapping, an innovative planning method, to the public
      health literature on community engagement by describing a pilot project with a
      new affordable housing development in Oakland, California between 2007 and 2009.
      Although ecocity mapping began as a paper technology, advances in geographic
      information systems (GIS) moved it forward. OBJECTIVES: This article describes
      how Ecocity Builders used GIS to conduct ecocity mapping to (1) assess vitality
      of neighborhoods and urban centers to prioritize community health intervention
      pilot sites and (2) create scenario maps for use in community health planning.
      METHODS: From fall 2007 to summer 2008, Ecocity Builders assessed neighborhood
      vitality using walking distance from parks, schools, rapid transit stops, grocery
      stores, and retail outlets. In 2008, ecocity maps were shared with residents to
      create a neighborhood health and sustainability plan. In 2009, Ecocity Builders
      developed scenario maps to show how changes to the built environment would
      improve air quality by reducing greenhouse gas emissions from vehicles, while
      increasing access to basic services and natural amenities. CONCLUSIONS: Community
      organizing with GIS was more useful than GIS alone for final site selection. GIS
      was useful in mapping scenarios after residents shared local neighborhood
      knowledge and ideas for change. Residents were interested in long-term
      environmental planning, provided they could meet immediate needs.

PMID- 23543029
TI  - Are there variances of calculated free testosterone attributed to variations in
      albumin and sex hormone-binding globulin concentrations in men?
AB  - OBJECTIVE: Calculated free testosterone (cFT) is determined from total
      testosterone (TT), sex hormone binding globulin (SHBG), and albumin (Alb) levels
      using mathematical formulae. Variations in cFT due to changes in SHBG or Alb have
      not been investigated. We evaluated potential cFT variances determined with fixed
      Alb (4.3 g/dL) and measured Alb, and the point at which low SHBG and Alb
      combinations produced significant cFT variance. METHOD: We analyzed 11,176 data
      points from 5,797 men. cFT values with fixed versus actual Alb values were
      evaluated and compared. cFT levels were theoretically determined for all possible
      combinations of TT, SHBG, and Alb (8,343,552 combinations). Agreement between the
      2 measures was assessed with Lin's concordance coefficient. RESULTS: Mean Alb was
      4.06 +/- 0.32 g/dL. Mean SHBG was 39.0 +/- 23.6 nmol/L. A fixed Alb of 4.3 g/dL
      did not produce significant variance for most cFT evaluations. Accuracy decreased
      when Alb was <=3.5 g/dL in combination with SHBG <=30 nmol/L, and this occurred
      in 1.2% of all data points. CONCLUSION: A fixed Alb of 4.3 g/dL is acceptable for
      most clinical evaluations. If Alb is <=3.5 g/dL and SHBG is <=30 nmol/L, the
      variance increases, and a free testosterone (FT) measurement by equilibrium
      dialysis is warranted for better accuracy.

PMID- 23543030
TI  - Persistence of Cushing's disease symptoms and comorbidities after surgical cure:
      a long-term, integral evaluation.
AB  - OBJECTIVES: Successful surgery does not always resolve all the clinical
      consequences of hypercortisolism in patients with Cushing's disease (CD). Our
      purpose was to integrally evaluate a group of CD patients cured by pituitary
      surgery and look for the persistence of CD symptoms, signs, and comorbidities.
      METHODS: We performed clinical and biochemical evaluations of 29 CD patients (2
      males) cured by pituitary surgery. All patients underwent early (median 12
      months) and late (median 58 months) postoperative evaluations. We sought
      information regarding hypercortisolism-related symptoms and signs, as well as
      metabolic, cardiovascular, reproductive, and psychologic comorbidities. RESULTS:
      The prevalence of obesity dropped from 72.4% at diagnosis to 31% at early
      evaluation but increased again to 44.8% at the late evaluation. Diabetes was
      present in 14 patients (48.3%) at diagnosis and persisted in 9 at the late
      evaluation. Hypertriglyceridemia was present in 58.6% and 55.1% of patients at
      diagnosis and at the late follow-up, respectively. The prevalence of
      hypercholesterolemia was 79.3% at diagnosis, decreased to 55.1% at the early
      evaluation, and increased to 65.5% at the late evaluation. Menstrual
      abnormalities were originally present in 15 of 20 women, and 8 of the 15 had
      recovered normal periods when seen at the last evaluation. Among the 24 patients
      with depression at diagnosis, 11 and 6 still exhibited mood abnormalities at the
      early and late evaluations, respectively. CONCLUSIONS: In a variable proportion
      of patients, the cardiovascular, metabolic, and emotional comorbidities of CD
      persist after long-term remission, irrespective of the initial degree of
      hypercortisolism.

PMID- 23543033
TI  - Child sexual abuse and adulthood-interpersonal outcomes: Examining pathways for
      intervention.
AB  - We examined a dual pathway, longitudinal mediational model in which child sexual
      abuse (CSA) influences adulthood-interpersonal functioning and sexual risk
      through its impact on resiliency resources and psychological distress. Women were
      recruited from two obstetrics and gynecological clinics serving primarily low
      income, inner-city women (N = 693) and interviewed at pretest (Time 1) and 6
      month follow-up (Time 2). The proposed mediators were resiliency resources (i.e.,
      self-esteem and self-efficacy) and psychological distress (i.e., depressive and
      posttraumatic stress symptoms). The interpersonal outcomes were general
      interpersonal problems (measured via recent loss of interpersonal resources, lack
      of perceived current social support, and recent social conflict) and HIV/sexual
      risk (measured via lack of confidence asserting safe-sex practices, intimate
      partner risk, and perceived barriers to safe sex). A respecified, partial
      structural equation model implying full mediation supported our hypotheses. Model
      fit was assessed using the chi-square goodness-of-fit statistic, comparative-fit
      index (CFI), root mean square error of approximation (RMSEA), and standardized
      root mean square residual (SRMR; CFI = .96, RMSEA = .05, SRMR = .04). The impact
      of CSA on interpersonal problems was mediated through its effect on psychological
      distress, whereas the impact of CSA on HIV/sexual risk was mediated through its
      effect on resiliency resources. Implications for intervention are discussed.
      (PsycINFO Database Record

PMID- 23543034
TI  - The Microbiological Profiles of Infected Prosthetic Implants with an Emphasis on
      the Organisms which Form Biofilms.
AB  - BACKGROUND: In spite of the decreasing incidence of orthopaedic device related
      infections to 1%, nowadays, device-related infections still remain a diagnostic,
      therapeutic and cost -related problem. AIMS AND OBJECTIVE: To record the common
      causative organisms and the contributing risk factors for orthopaedic device
      related infections in a tertiary care teaching hospital. METHODS: In a
      prospective study, fifty patients who underwent orthopaedic device implantation
      from Jan 2009 - June 2010 were enrolled; among them, 42 patients were complicated
      with infections. The demography, microbiological data, treatment and the outcome
      of each patient were recorded. STATISTICAL ANALYSIS: The data was analyzed in
      terms of frequency and percentage. RESULTS: Of the 50 samples, 42(84%) were
      culture positive, while 8(16%) were cultures negative. The femur was the most
      commonly affected bone in both males (median age-37.1yrs) and females (median age
      41.3 yrs). Staphylococcus aureus was the organism which was most commonly
      isolated and which caused biofilms, followed by non-fermenting, gram negative
      bacilli and Klebsiella spp. We reported the first case till date in the
      literature of Candida krusei PJI, to the best of our knowledge. No anaerobes were
      isolated. Tissue trauma, open fractures, post-operative surgical site infections
      and Diabetes mellitus were found to be the important risk factors. The biofilm
      forming organisms were commonly associated with polymicrobial infections and even
      an aggressive antibiotic therapy was often inadequate to eliminate the
      infections. A conservative surgical treatment was associated with treatment
      failures. Implant removal or replacement was required in most of the cases to
      eradicate the infection. CONCLUSION: The most common bacteria which were isolated
      included Staphylococcus aureus, followed by Pseudomonas aeruginosa and
      Klebsiella. A majority of them are resistant to the commonly used antibiotics,
      leading to treatment failures which necessitated an implant removal.

PMID- 23543035
TI  - The use of procalcitonin as a marker of sepsis in children.
AB  - OBJECTIVE: Sepsis is a life-threatening disease which is associated with high
      rates of morbidity and mortality. The critically ill patients often manifest a
      Systemic Inflammatory Response Syndrome (SIRS) which is independent of an
      infection. The early diagnosis of different severities of sepsis is important for
      an early implementation of the specific therapies. Our objective was to evaluate
      the diagnostic and the prognostic values of blood Procalcitonin (PCT) in cases of
      bacterial septicaemia in children. METHODS: The total sample comprised of 150
      subjects who were admitted to the ICU with septicaemia and 50 normal, healthy,
      age and sex matched children. The first sample was collected at the time of
      admission, before the start of the antibiotic therapy (T0). A second sample was
      collected at 24 hours (T24) and a final sample was collected at 96 hours (T96). A
      PCT value of > 0.5ng/ml was accepted as positive. RESULTS: 63% of the children
      who were diagnosed with a bacterial aetiology showed detectable blood PCT levels
      with higher concentrations, while in the children who were diagnosed with a viral
      aetiology, only 22.2 % had detectable PCT levels, but in lower concentrations.
      The mean percentage reduction in the PCT value among the bacterial infection
      subjects was 44.39 +/- 41.82 as compared to that in the viral infection subjects
      (5.71 +/- 26.68) and in the subjects where the aetiology was not established
      (5.71 +/- 26.68). CONCLUSION: The results which were obtained in our study con-
      firmed that the PCT levels were a better marker for the bacterial infections. The
      PCT measurements may be used as a guide to the antibiotic therapy in critically
      ill children with suspected sepsis.

PMID- 23543032
TI  - Replication of telomeres and the regulation of telomerase.
AB  - Telomeres are the physical ends of eukaryotic chromosomes. They protect
      chromosome ends from DNA degradation, recombination, and DNA end fusions, and
      they are important for nuclear architecture. Telomeres provide a mechanism for
      their replication by semiconservative DNA replication and length maintenance by
      telomerase. Through telomerase repression and induced telomere shortening,
      telomeres provide the means to regulate cellular life span. In this review, we
      introduce the current knowledge on telomere composition and structure. We then
      discuss in depth the current understanding of how telomere components mediate
      their function during semiconservative DNA replication and how telomerase is
      regulated at the end of the chromosome. We focus our discussion on the telomeres
      from mammals and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces
      pombe.

PMID- 23543036
TI  - Sodium valproate induced increased frequency of micturition and enuresis.
AB  - Sodium valproate is a commonly used antiepileptic drug (AED) for control of a
      broad range of seizures. Adverse drug reactions (ADR) due to sodium valproate
      range from sedation to nausea, vomiting, weight gain, idiosyncratic adverse
      effects like hepatotoxicity and life threatening conditions like pancreatitis. We
      present a case of sodium valproate induced enuresis in child. This ADR of
      valproate is an underreported ADR and requires special attention of pediatricians
      as it can interfere with the further treatment of the disease.

PMID- 23543037
TI  - Acid-mediated tumour cell invasion: a discrete modelling approach using the
      extended Potts model.
AB  - Acidic extracellular pH has been shown to play a crucial part in the invasive and
      metastatic cascade of some tumours. In this study, we examine the effect of
      extracellular acidity on tumour invasion focusing, in particular, on cellular
      adhesion, proteolytic enzyme activity and cellular proliferation. Our numerical
      simulations using a cellular Potts model show that, under acidic extracellular
      pH, changes in cell-matrix adhesion strength has a comparable effect on tumour
      invasiveness as the increase in proteolytic enzyme activity. We also show that
      tumour cells cultured under physiological pH tend to be large and the tumours
      develop a "diffuse" morphology compared to those cultured at acidic pH, which
      display protruding "fingers" at the advancing front. A key model prediction is
      the observation that the main effect on invasion from culturing cells at low
      extracellular pH stems from changes in the intercellular and cell-matrix adhesion
      strengths and proteolytic enzyme secretion rate. However, we show that the
      effects of proteolysis needs to be significant as low to moderate changes only
      has nominal effects on cell invasiveness. We find that the low pH e effects on
      cell size and proliferation rate have much lower influence on cell invasiveness. 

PMID- 23543039
TI  - A Consanguinity Related Autosomal Translocation which Leads to Premature Ovarian
      Failure.
AB  - The premature ovarian failures with underlying chromosomal abnormalities are
      normally X-linked, although their associations with the autosomal and the
      Robertsonian translocations are also possible. Here, we are reporting a case of
      premature ovarian failure which was associated with a translocation between the
      long arm of chromosome 7 at q11.23 and the short arm of chromosome 5 at p15.3.
      The proband was a 26-year-old Malay woman who presented with premature ovarian
      failure, who was referred for cytogenetic testing due to the suspicion of a
      chromosomal anomaly. Her physical examination revealed that she had no abdominal
      or pelvic masses and that she had normal secondary sexual characteristics. Her
      medical history as well, revealed no points for concern. However, a
      consanguineous relationship existed, as the patient's paternal grandmother and
      maternal grandfather were biological cousins. Our present case indicated that
      region p15.3 of chromosome 5 and region q11.23 of chromosome 7 possibly carried
      essential genes for the ovarian function and that they postulated a link between
      the consanguinity and the chromosomal abnormalities.

PMID- 23543038
TI  - Neurotransmitter CART as a New Therapeutic Candidate for Parkinson's Disease.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To
      date, there is no effective treatment that halts its progression. Increasing
      evidence indicates that mitochondria play an important role in the development of
      PD. Hence mitochondria-targeted approaches or agents may have therapeutic promise
      for treatment of the disease. Neuropeptide CART (cocaine-amphetamine-regulated
      transcript), a hypothalamus and midbrain enriched neurotransmitter with an
      antioxidant property, can be found in mitochondria, which is the main source of
      reactive oxygen species. Systemic administration of CART has been found to
      ameliorate dopaminergic neuronal loss and improve motor functions in a mouse
      model of PD. In this article, we summarize recent progress in studies
      investigating the relationship between CART, dopamine, and the pathophysiology of
      PD, with a focus on mitochondria-related topics. 

PMID- 23543040
TI  - Para-clinico-pathological observations of insidious incidence of canine
      hepatozoonosis from a mongrel dog: a case report.
AB  - A rare case of canine hepatozoonosis in a mongrel dog with para-clinico
      pathological observations has been reported. The study included detailed haemato
      biochemical changes at two stages, i.e. before treatment and after treatment with
      adopted therapy. Before therapy, blood picture revealed normocytic hypochromic
      anaemia and neutrophilic leucocytosis with variable counts of platelets. Thirty
      seven percent of neutrophils were found infected with gametocytes of Hepatozoon
      canis. Following treatment, further decrease in haemoglobin value with a relative
      increase in lymphocyte count was seen. Biochemically, increase in alkaline
      phosphatase, blood urea nitrogen and creatinine levels along with
      hyperproteinemia was seen. The 14 days chemotherapy did not bring a respite for
      the dog and the level of parasitaemia was 33% after the treatment. The alkaline
      phosphatase and creatinine level further rose up following therapy with
      sulphadiazine and clindamycin. Continual study is required to explain the best
      possible therapeutic combination to deal H. canis.

PMID- 23543041
TI  - Opportunities for optimization of in-field water harvesting to cope with changing
      climate in semi-arid smallholder farming areas of Zimbabwe.
AB  - Climate change has resulted in increased vulnerability of smallholder farmers in
      marginal areas of Zimbabwe where there is limited capacity to adapt to changing
      climate. One approach that has been used to adapt to changing climate is in-field
      water harvesting for improved crop yields in the semi- arid regions of Zimbabwe.
      This review analyses the history of soil and water conservation in Zimbabwe,
      efforts of improving water harvesting in the post independence era, farmer driven
      innovations, water harvesting technologies from other regions, and future
      directions of water harvesting in semi arid marginal areas. From this review it
      was observed that the blanket recommendations that were made on the early
      conservation method were not suitable for marginal areas as they resulted in
      increased losses of the much needed water. In the late 1960 and 70s', soil and
      water conservation efforts was a victim of the political environment and this
      resulted in poor uptake. Most of the water harvesting innovations which were
      promoted in the 1990s' and some farmer driven innovations improved crop yields in
      marginal areas but were poorly taken up by farmers because they are labour
      intensive as the structures should be made annually. To address the challenges of
      labour shortages, the use of permanent in-field water harvesting technologies are
      an option. There is also need to identify ways for promoting water harvesting
      techniques that have been proven to work and to explore farmer-led knowledge
      sharing platforms for scaling up proven technologies. 

PMID- 23543042
TI  - Sleep quality in patients on maintenance hemodialysis and peritoneal dialysis.
AB  - BACKGROUND: Sleep disturbances are common among uremic patients; however, limited
      data are available on predictors of sleep quality in this population. We assessed
      sleep quality in patients on hemodialysis (HD) and peritoneal dialysis (PD) and
      investigated predictors related to sleep quality. METHODS: Patients on
      maintenance HD and PD were consecutively included from two medical centers in
      Isfahan city (Iran). They completed the Pittsburgh sleep quality index (PSQI) and
      hospital anxiety and depression scale. Laboratory tests were done for iron state,
      kidney function, and electrolytes. Univariate and multivariate analyses were
      performed to find predictors of sleep quality. RESULTS: About 90 patients were
      evaluated (53 males, age = 54.2 +/- 15.2 years, disease duration = 5.3 +/- 4.5
      years). Poor sleep quality was frequent in 86.6% of the cases in each group of HD
      and PD patients. Patients on HD had poorer sleep quality in terms of total PSQI
      scores and two dimensions of sleep latency and sleep efficiency (P < 0.05).
      Anxiety (beta = 0.232, P = 0.027), depression (beta = 0.317, P = 0.004), and
      being on HD (beta = 2.095, P = 0.009) were independent predictors of overall poor
      sleep quality. CONCLUSIONS: Poor sleep quality is highly frequent in patients on
      maintenance dialysis and mood disorders and being on HD are predictive factors.
      Further studies are required for better understanding of risk factors associated
      with poor sleep quality and thus possible treatments in these patients.

PMID- 23543043
TI  - Duocentric(r) reversed shoulder prosthesis and Personal Fit(r) templates:
      innovative strategies to optimize prosthesis positioning and prevent scapular
      notching.
AB  - We describe our experience with a new system of patient-specific template called
      Personal Fit((r)), which is unique in shoulder surgery and used in combination
      with Duocentric((r)) prosthesis. The reverse prosthesis's concept is the
      invention of Paul Grammont, developed with Grammont's team of Dijon University as
      from 1981, which led to the first reversed total shoulder prosthesis called
      Trumpet in 1985. The Duocentric((r)) prosthesis developed in 2001 is the third
      generation prosthesis, coming from the Trumpet and the second-generation
      prosthesis Delta((r)) (DePuy). This prosthesis provides a novel solution to the
      notching problem with an inferior overhang integrated onto the glenoid baseplate.
      Personal Fit((r)) system is based on reconstructing the shoulder joint bones in
      three dimensions using CT scan data, placing a landmark on the scapula and
      locating points on the glenoid and humerus. That will be used as a reference for
      the patient-specific templates. We study the glenoid position planned with
      Personal Fit((r)) software relative to native glenoid position in 30 cases. On
      average, the difference between the planned retroversion (or anteversion in one
      case) and native retroversion was 8.6 degrees . 

PMID- 23543044
TI  - Currents of plate osteosynthesis in osteoporotic bone.
AB  - Osteoporotic fractures are becoming more prevalent with ageing of populations
      worldwide. Inadequate fixation or prolonged immobilization after non-surgical
      care leads to serious life-threatening events, poor functional results and
      lifelong disability. Thus, a stable internal fixation and rapid initiation of
      rehabilitation are required for faster return of function. Conventional internal
      fixation attempts to achieve the exact anatomy, often with extended soft-tissue
      stripping and compression of the periosteum, causing disturbance of the
      metaphyseal and comminuted fracture's bone blood supply. This technique relies on
      frictional forces between bone and plate. Osteoporotic bone might not be able to
      generate enough torque with the screw to securely fix the plate to bone. Thus,
      this surgical management have resulted in increased incidence of poor results in
      elderly, osteoporotic patients. The newly developed locked internal fixators,
      locking compression plates and less invasive stabilization system, consist of
      plate and screw systems where the screws are locked in the plate, minimizing the
      compressive forces exerted between plate and bone. Thus, the plate does not need
      to compress the bone nor requires precise anatomical contouring of a plate
      disturbing the periosteal blood supply. These fixators allowed the development of
      the minimal invasive percutaneous osteosynthesis. Nowadays, locking plates are
      the fixation method of choice for osteoporotic, diaphyseal or metaphyseal,
      severely comminuted fractures. 

PMID- 23543045
TI  - The physiology of rainbow trout in social hierarchies: two ways of looking at the
      same data.
AB  - Salmonids form dominance hierarchies in environments, where space or food are
      limiting. Our first objective was to investigate the physiology of individual
      rainbow trout in 4-fish hierarchies. Our second was to compare conclusions drawn
      from grouping physiological data on the basis of social rank with those based on
      relating individual physiology to individual aggressive behavior. To create a
      social hierarchy, groups of 4 juvenile trout were fed (1 % ration) using a
      darkened feeding container, twice daily (morning and evening). Each morning
      feeding was videotaped to record aggressive behavior, thereby facilitating the
      assignment of a social status rank to each fish. On days 5 and 10-11,
      physiological parameters were measured in fish fasted for 24 h. Social
      hierarchies formed in all tested groups. One fish would become dominant, whereas
      the three subordinate individuals would each assume a stable social rank. When
      classified according to this social rank, the three subordinate individuals all
      displayed similar physiology, different from the physiology of the dominant fish.
      The latter included higher ammonia excretion rate, greater protein utilization in
      aerobic metabolism, greater feeding, higher specific growth rate, greater
      increase in condition factor, and lower routine oxygen consumption rate. However,
      when individual aggression was taken into account, a continuous gradient was
      observed between aggression and physiology for most parameters, regardless of
      social status. These relationships could be improved by normalizing the
      aggression score to the overall level of aggression in each hierarchy. We argue
      that individual behavior should be considered instead of just social rank when
      studying the physiology of trout in social hierarchies. 

PMID- 23543046
TI  - Premature rupture of membrane at term: early induction versus expectant
      management.
AB  - INTRODUCTION: Premature rupture of membrane is managed either expectantly or
      actively. The purpose of the study was to assess the effectiveness of early labor
      induction with cervical prostaglandin E2 versus expectant management in women
      with term premature rupture of membrane. MATERIAL AND METHODS: Singleton
      pregnancy cases with cephalic presentation reported between 37 and 41 weeks of
      pregnancy with PROM of <6 h and cervical dilatation <3 cm were studied over a
      period of 2 years. Out of 100 patients studied, half of them were managed by
      expectant protocol and the other half by early induction within 6 h of PROM with
      intracervical gel. Main outcomes measured were PROM-delivery interval, mode of
      delivery, neonatal and maternal morbidity, and period of maternal and/or neonatal
      hospitalization. Chi-square test was used to compare frequencies between two
      groups. Differences between means of other measurement were compared by
      independent t test. RESULTS: PROM-delivery interval was 22 h in expectant group,
      while in early induction group, it was 13 h (p value < 0.001). Rate of cesarean
      section remained almost same in both groups. Increases in maternal-neonatal
      infection rate and hospital stay were noted in expectant group; however, this was
      not statistically significant. CONCLUSION: Immediate labor induction with
      prostaglandin in cases of term PROM shortens delivery interval and maternal
      hospital stay with reduction in maternal-neonatal sepsis.

PMID- 23543047
TI  - Firing pattern and synchronization property analysis in a network model of the
      olfactory bulb.
AB  - In the olfactory system, both the temporal spike structure and spatial
      distribution of neuronal activity are important for processing odor information.
      In this paper, a biophysically-detailed, spiking neuronal model is used to
      simulate the activity of olfactory bulb. It is shown that by varying some key
      parameters such as maximal conductances of Ks and Nap the spike train of single
      neuron can exhibit various firing patterns. Synchronization in coupled neurons is
      also investigated as the coupling strength varying in the situation of two
      neurons and network. It is illustrated that the coupled neurons can exhibit
      different types of pattern when the coupling strength varies. These results may
      be instructive to understand information transmission in olfactory system.

PMID- 23543048
TI  - The diversity of anti-microbial secondary metabolites produced by fungal
      endophytes: an interdisciplinary perspective.
AB  - Endophytes are microbes that inhabit host plants without causing disease and are
      reported to be reservoirs of metabolites that combat microbes and other
      pathogens. Here we review diverse classes of secondary metabolites, focusing on
      anti-microbial compounds, synthesized by fungal endophytes including terpenoids,
      alkaloids, phenylpropanoids, aliphatic compounds, polyketides, and peptides from
      the interdisciplinary perspectives of biochemistry, genetics, fungal biology,
      host plant biology, human and plant pathology. Several trends were apparent.
      First, host plants are often investigated for endophytes when there is prior
      indigenous knowledge concerning human medicinal uses (e.g., Chinese herbs).
      However, within their native ecosystems, and where investigated, endophytes were
      shown to produce compounds that target pathogens of the host plant. In a few
      examples, both fungal endophytes and their hosts were reported to produce the
      same compounds. Terpenoids and polyketides are the most purified anti-microbial
      secondary metabolites from endophytes, while flavonoids and lignans are rare.
      Examples are provided where fungal genes encoding anti-microbial compounds are
      clustered on chromosomes. As different genera of fungi can produce the same
      metabolite, genetic clustering may facilitate sharing of anti-microbial secondary
      metabolites between fungi. We discuss gaps in the literature and how more
      interdisciplinary research may lead to new opportunities to develop bio-based
      commercial products to combat global crop and human pathogens.

PMID- 23543049
TI  - Replication study for the association of 3 SNP loci identified in a genome-wide
      association study for diabetic nephropathy in European type 1 diabetes with
      diabetic nephropathy in Japanese patients with type 2 diabetes.
AB  - BACKGROUND: A recent genome-wide association study for diabetic nephropathy in
      European type 1 diabetes identified 3 candidate loci for diabetic nephropathy. In
      this study, we examined the association of the 3 single nucleotide polymorphism
      (SNP) loci with susceptibility to diabetic nephropathy in Japanese subjects with
      type 2 diabetes. METHODS: We genotyped 3 SNPs, rs7583877 in AFF3, rs12437854 in
      the RGMA-MCTP2 locus and rs7588550 in ERBB4, for 2,300 Japanese patients with
      type 2 diabetes [initial study, 1,055 nephropathy cases with overt proteinuria or
      with end-stage renal disease (ESRD) and 1,245 control patients with
      normoalbuminuria]. The association of these SNPs with diabetic nephropathy was
      examined by using a logistic regression analysis. RESULTS: We observed a
      significant association of rs7588550 in ERBB4 with diabetic nephropathy in the
      Japanese patients with type 2 diabetes, although the effect direction was not
      consistent with that in the European study [p = 0.0126, odds ratio (OR) = 0.79,
      95 % confidence interval (CI): 0.65-0.95]. We further examined the association of
      rs7588550 with diabetic nephropathy in an independent Japanese cohort (596
      nephropathy cases and 311 controls) and observed the same trend of the
      association with the initial study. We did not observe any association of the
      remaining 2 SNP loci with diabetic nephropathy in the present Japanese sample.
      CONCLUSION: The association of SNP loci derived from GWAS in European type 1
      diabetes with diabetic nephropathy was not replicated in the Japanese patients
      with type 2 diabetes, although the ERBB4 locus may have some effect also in
      Japanese type 2 diabetes.

PMID- 23543050
TI  - Small renal size in newborns with spina bifida: possible causes.
AB  - BACKGROUND: Previous studies reported that children with neural tube defects, but
      without any history of intrinsic renal diseases, have small kidneys when compared
      with age-matched standard renal growth. The aim of this study was to investigate
      the possible causes of small renal size in children with spina bifida by
      comparing growth hormone deficiency, physical limitations and
      hyperhomocysteinemia. METHODS: The sample included 187 newborns with spina
      bifida. Renal sizes in the patients were assessed by using maximum measurement of
      renal length and the measurements were compared by using the Sutherland monogram.
      According to the results, the sample was divided into two groups--a group of 120
      patients with small kidneys (under the third percentile) and a control group of
      67 newborns with normal kidney size. Plasma total homocysteine was investigated
      in mothers and in their children. Serum insulin-like growth factor-1 (IGF-1)
      levels were measured. RESULTS: Serum IGF-1 levels were normal in both groups.
      Children and mothers with homocysteine levels >10 MUmol/l were more than twice as
      likely to have small kidneys and to give to birth children with small kidneys,
      respectively, compared with newborns and mothers with homocysteine levels <10
      MUmol/l. An inverse correlation was also found between the homocysteine levels of
      mothers and kidney sizes of children (r = - 0.6109 P <= 0.01). CONCLUSIONS: It is
      highly important for mothers with hyperhomocysteinemia to be educated about
      benefits of folate supplementation in order to reduce the risk of small renal
      size and lower renal function in children.

PMID- 23543051
TI  - Long-term follow-up of acute isolated accommodation insufficiency.
AB  - PURPOSE: To define the long-term results of accommodation insufficiency and to
      investigate the correlation between accommodation insufficiency and other factors
      including near point of convergence (NPC), age, and refractive errors. METHODS:
      From January 2008 to December 2009, 11 patients with acute near vision
      disturbance and remote near point of accommodation (NPA) were evaluated. Full
      ophthalmologic examinations, including best corrected visual acuity, manifest
      refraction and prism cover tests were performed. Accommodation ability was
      measured by NPA using the push-up method. We compared accommodation insufficiency
      and factors including age, refractive errors and NPC. We also investigated the
      recovery from loss of accommodation in patients. RESULTS: Mean age of patients
      was 20 years (range, 9 to 34 years). Five of the 11 patients were female. Mean
      refractive error was -0.6 diopters (range, -3.5 to +0.25 diopters) and 8 of 11
      patients (73%) had emmetropia (+0.50 to -0.50 diopters). No abnormalities were
      found in brain imaging tests. Refractive errors were not correlated with NPA or
      NPC (rho = 0.148, p = 0.511; rho = 0.319, p = 0.339; respectively). The
      correlation between age and NPA was not significant (rho = -395, p = 0.069).
      However, the correlation between age and NPC was negative (rho = -0.508, p =
      0.016). Three of 11 patients were lost to follow-up, and 6 of 8 patients had
      permanent insufficiency of accommodation. CONCLUSIONS: Accommodation
      insufficiency is most common in emmetropia, however, refractive errors and age
      are not correlated with accommodation insufficiency. Dysfunction of accommodation
      can be permanent in the isolated accommodation insufficiency.

PMID- 23543052
TI  - Recurrent hypoglycemia: boosting the brain's metabolic flexibility.
AB  - For people with diabetes, recurrent episodes of hypoglycemia limit the brain's
      ability to sense dangerously low blood sugar levels. In this issue of the JCI,
      the mechanisms behind this clinical problem of hypoglycemia unawareness are
      addressed by Herzog et al. The authors provide compelling evidence that recurrent
      hypoglycemia enhances transport of lactate into the brain and, although not
      itself a major alternative fuel source, lactate may preserve neuronal function
      during hypoglycemia by maintaining neuronal glucose metabolism. These findings
      redefine our understanding of the brain's metabolic adaptations that result from
      recurrent hypoglycemia.

PMID- 23543053
TI  - The phosphatase CD148 promotes airway hyperresponsiveness through SRC family
      kinases.
AB  - Increased airway smooth muscle (ASM) contractility and the development of airway
      hyperresponsiveness (AHR) are cardinal features of asthma, but the signaling
      pathways that promote these changes are poorly understood. Tyrosine
      phosphorylation is tightly regulated by the opposing actions of protein tyrosine
      kinases and phosphatases, but little is known about whether tyrosine phosphatases
      influence AHR. Here, we demonstrate that genetic inactivation of receptor-like
      protein tyrosine phosphatase J (Ptprj), which encodes CD148, protected mice from
      the development of increased AHR in two different asthma models. Surprisingly,
      CD148 deficiency minimally affected the inflammatory response to allergen, but
      significantly altered baseline pulmonary resistance. Mice specifically lacking
      CD148 in smooth muscle had decreased AHR, and the frequency of calcium
      oscillations in CD148-deficient ASM was substantially attenuated, suggesting that
      signaling pathway alterations may underlie ASM contractility. Biochemical
      analysis of CD148-deficient ASM revealed hyperphosphorylation of the C-terminal
      inhibitory tyrosine of SRC family kinases (SFKs), implicating CD148 as a critical
      positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM
      contractility could be mimicked by treatment of both mouse trachea and human
      bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it
      regulates in ASM as potential targets for the treatment of AHR.

PMID- 23543054
TI  - SLITRK6 mutations cause myopia and deafness in humans and mice.
AB  - Myopia is by far the most common human eye disorder that is known to have a
      clear, albeit poorly defined, heritable component. In this study, we describe an
      autosomal-recessive syndrome characterized by high myopia and sensorineural
      deafness. Our molecular investigation in 3 families led to the identification of
      3 homozygous nonsense mutations (p.R181X, p.S297X, and p.Q414X) in SLIT and NTRK
      like family, member 6 (SLITRK6), a leucine-rich repeat domain transmembrane
      protein. All 3 mutant SLITRK6 proteins displayed defective cell surface
      localization. High-resolution MRI of WT and Slitrk6-deficient mouse eyes revealed
      axial length increase in the mutant (the endophenotype of myopia). Additionally,
      mutant mice exhibited auditory function deficits that mirrored the human
      phenotype. Histological investigation of WT and Slitrk6-deficient mouse retinas
      in postnatal development indicated a delay in synaptogenesis in Slitrk6-deficient
      animals. Taken together, our results showed that SLITRK6 plays a crucial role in
      the development of normal hearing as well as vision in humans and in mice and
      that its disruption leads to a syndrome characterized by severe myopia and
      deafness.

PMID- 23543055
TI  - Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of
      ERBB3.
AB  - The mechanisms underlying adaptive resistance of melanoma to targeted therapies
      remain unclear. By combining ChIP sequencing with microarray-based gene
      profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription
      factor that promotes resistance to RAF inhibitors in melanoma. Enhanced ERBB3
      signaling promoted resistance to RAF pathway inhibitors in cultured melanoma cell
      lines and in mouse xenograft models. ERBB3 signaling was dependent on ERBB2;
      targeting ERBB2 with lapatinib in combination with the RAF inhibitor PLX4720
      reduced tumor burden and extended latency of tumor regrowth in vivo versus
      PLX4720 alone. These results suggest that enhanced ERBB3 signaling may serve as a
      mechanism of adaptive resistance to RAF and MEK inhibitors in melanoma and that
      cotargeting this pathway may enhance the clinical efficacy and extend the
      therapeutic duration of RAF inhibitors.

PMID- 23543056
TI  - Lactate preserves neuronal metabolism and function following antecedent recurrent
      hypoglycemia.
AB  - Hypoglycemia occurs frequently during intensive insulin therapy in patients with
      both type 1 and type 2 diabetes and remains the single most important obstacle in
      achieving tight glycemic control. Using a rodent model of hypoglycemia, we
      demonstrated that exposure to antecedent recurrent hypoglycemia leads to
      adaptations of brain metabolism so that modest increments in circulating lactate
      allow the brain to function normally under acute hypoglycemic conditions. We
      characterized 3 major factors underlying this effect. First, we measured enhanced
      transport of lactate both into as well as out of the brain that resulted in only
      a small increase of its contribution to total brain oxidative capacity,
      suggesting that it was not the major fuel. Second, we observed a doubling of the
      glucose contribution to brain metabolism under hypoglycemic conditions that
      restored metabolic activity to levels otherwise only observed at euglycemia.
      Third, we determined that elevated lactate is critical for maintaining glucose
      metabolism under hypoglycemia, which preserves neuronal function. These
      unexpected findings suggest that while lactate uptake was enhanced, it is
      insufficient to support metabolism as an alternate substrate to replace glucose.
      Lactate is, however, able to modulate metabolic and neuronal activity, serving as
      a "metabolic regulator" instead.

PMID- 23543057
TI  - Cooperativity of imprinted genes inactivated by acquired chromosome 20q
      deletions.
AB  - Large regions of recurrent genomic loss are common in cancers; however, with a
      few well-characterized exceptions, how they contribute to tumor pathogenesis
      remains largely obscure. Here we identified primate-restricted imprinting of a
      gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid
      malignancies. We showed that a single heterozygous 20q deletion consistently
      resulted in the complete loss of expression of the imprinted genes L3MBTL1 and
      SGK2, indicative of a pathogenetic role for loss of the active paternally
      inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated
      erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic
      myeloid malignancies, with distinct consequences in each lineage. We demonstrated
      that L3MBTL1 and SGK2 collaborated in the transcriptional regulation of MYC by
      influencing different aspects of chromatin structure. L3MBTL1 is known to
      regulate nucleosomal compaction, and we here showed that SGK2 inactivated BRG1, a
      key ATP-dependent helicase within the SWI/SNF complex that regulates nucleosomal
      positioning. These results demonstrate a link between an imprinted gene cluster
      and malignancy, reveal a new pathogenetic mechanism associated with acquired
      regions of genomic loss, and underline the complex molecular and cellular
      consequences of "simple" cancer-associated chromosome deletions.

PMID- 23543058
TI  - Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5.
AB  - Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease
      caused by mutations in dystrophin. The degree of functional deterioration in
      muscle stem cells determines the severity of DMD. The mitogen-activated protein
      kinases (MAPKs), which are inactivated by MAPK phosphatases (MKPs), represent a
      central signaling node in the regulation of muscle stem cell function. Here we
      show that the dual-specificity protein phosphatase DUSP10/MKP-5 negatively
      regulates muscle stem cell function in mice. MKP-5 controlled JNK to coordinate
      muscle stem cell proliferation and p38 MAPK to control differentiation. Genetic
      loss of Mkp5 in mice improved regenerative myogenesis and dystrophin-deficient
      mdx mice lacking Mkp5 exhibited an attenuated dystrophic muscle phenotype. Hence,
      enhanced promyogenic MAPK activity preserved muscle stem cell function even in
      the absence of dystrophin and ultimately curtailed the pathogenesis associated
      with DMD. These results identify MKP-5 as an essential negative regulator of the
      promyogenic actions of the MAPKs and suggest that MKP-5 may serve as a target to
      promote muscle stem cell function in the treatment of degenerative skeletal
      muscle diseases.

PMID- 23543061
TI  - Bruce Beutler wins the 2013 ASCI/Stanley J. Korsmeyer Award. Interview by Kathryn
      Claiborn.

PMID- 23543059
TI  - Discovering naturally processed antigenic determinants that confer protective T
      cell immunity.
AB  - CD8+ T cells (TCD8) confer protective immunity against many infectious diseases,
      suggesting that microbial TCD8 determinants are promising vaccine targets.
      Nevertheless, current T cell antigen identification approaches do not discern
      which epitopes drive protective immunity during active infection - information
      that is critical for the rational design of TCD8-targeted vaccines. We employed a
      proteomics-based approach for large-scale discovery of naturally processed
      determinants derived from a complex pathogen, vaccinia virus (VACV), that are
      presented by the most frequent representatives of four major HLA class I
      supertypes. Immunologic characterization revealed that many previously
      unidentified VACV determinants were recognized by smallpox-vaccinated human
      peripheral blood cells in a variegated manner. Many such determinants were
      recognized by HLA class I-transgenic mouse immune TCD8 too and elicited
      protective TCD8 immunity against lethal intranasal VACV infection. Notably,
      efficient processing and stable presentation of immune determinants as well as
      the availability of naive TCD8 precursors were sufficient to drive a
      multifunctional, protective TCD8 response. Our approach uses fundamental insights
      into T cell epitope processing and presentation to define targets of protective
      TCD8 immunity within human pathogens that have complex proteomes, suggesting that
      this approach has general applicability in vaccine sciences.

PMID- 23543060
TI  - MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in
      atrial fibrillation.
AB  - Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced
      morbidity and mortality. Inward-rectifier K+ current (IK1) is believed to be an
      important regulator of reentrant-spiral dynamics and a major component of AF
      related electrical remodeling. MicroRNA-26 (miR-26) is predicted to target the
      gene encoding KIR2.1, KCNJ2. We found that miR-26 was downregulated in atrial
      samples from AF animals and patients and this downregulation was accompanied by
      upregulation of IK1/KIR2.1 protein. miR-26 overexpression suppressed expression
      of KCNJ2/KIR2.1. In contrast, miR-26 knockdown, inhibition, or binding-site
      mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-26 target.
      Knockdown of endogenous miR-26 promoted AF in mice, whereas adenovirus-mediated
      expression of miR-26 reduced AF vulnerability. Kcnj2-specific miR-masks
      eliminated miR-26-mediated reductions in Kcnj2, abolishing miR-26's protective
      effects, while coinjection of a Kcnj2-specific miR-mimic prevented miR-26
      knockdown-associated AF in mice. Nuclear factor of activated T cells (NFAT), a
      known actor in AF-associated remodeling, was found to negatively regulate miR-26
      transcription. Our results demonstrate that miR-26 controls the expression of
      KCNJ2 and suggest that this downregulation may promote AF.

PMID- 23543062
TI  - A mitochondrial bioenergetic etiology of disease.
AB  - The classical Mendelian genetic perspective has failed to adequately explain the
      biology and genetics of common metabolic and degenerative diseases. This is
      because these diseases are primarily systemic bioenergetic diseases, and the most
      important energy genes are located in the cytoplasmic mitochondrial DNA (mtDNA).
      Therefore, to understand these "complex" diseases, we must investigate their
      bioenergetic pathophysiology and consider the genetics of the thousands of copies
      of maternally inherited mtDNA, the more than 1,000 nuclear DNA (nDNA)
      bioenergetic genes, and the epigenomic and signal transduction systems that
      coordinate these dispersed elements of the mitochondrial genome.

PMID- 23543063
TI  - IL-6 polymorphisms: a useful genetic tool for inflammation research?
AB  - In 1998, we described a novel polymorphism in the promoter (G>C, rs1800795) of
      the IL-6 (IL6) gene. The common allele, G, exhibited higher transcriptional
      activity in gene reporter assays and was associated with higher serum IL-6 levels
      in a small cohort of healthy subjects. We explored the ethnic distribution of
      these alleles and found significant differences among people of mixed European
      descent, Africans, and Gujarati Asians. Disease association was established in a
      cohort of 92 children of mixed European descent from the United Kingdom with
      systemic juvenile idiopathic arthritis (sJIA), with the GG genotype being
      significantly increased in sJIA cases compared with that in 383 controls,
      especially in those under 6 years old (P = 0.01). This polymorphism has since
      been used as a functional variant to explore the role of elevated IL-6 levels in
      many common disease states, confirming the key causal role of IL-6 in human
      health and disease.

PMID- 23543065
TI  - Paediatric research and the communication of not-so incidental findings.
AB  - Paediatric research may well be the first field in which the ethical implications
      of next-generation sequencing (NGS) will be appreciated. Allowing as it does for
      the revelation of much more than just the disease gene being researched, the
      advent of NGS will require careful consideration of the return of research
      results and incidental findings to parents. In contrast to the choices offered to
      adults with regard to the return of both research results and incidental
      findings, the same does not hold true for children. Parents must act in their
      'medical' best interests. Current policy guidance on this issue in Canada is
      unclear.

PMID- 23543066
TI  - A novel method for assessing the development of speech motor function in toddlers
      with autism spectrum disorders.
AB  - There is increasing evidence to show that indicators other than socio-cognitive
      abilities might predict communicative function in Autism Spectrum Disorders
      (ASD). A potential area of research is the development of speech motor function
      in toddlers. Utilizing a novel measure called "articulatory features," we assess
      the abilities of toddlers to produce sounds at different timescales as a metric
      of their speech motor skills. In the current study, we examined (1) whether
      speech motor function differed between toddlers with ASD, developmental delay
      (DD), and typical development (TD); and (2) whether differences in speech motor
      function are correlated with standard measures of language in toddlers with ASD.
      Our results revealed significant differences between a subgroup of the ASD
      population with poor verbal skills, and the other groups, for the articulatory
      features associated with the shortest-timescale, namely place of articulation
      (POA), (p < 0.05). We also found significant correlations between articulatory
      features and language and motor ability as assessed by the Mullen and the
      Vineland scales for the ASD group. Our findings suggest that articulatory
      features may be an additional measure of speech motor function that could
      potentially be useful as an early risk indicator of ASD.

PMID- 23543067
TI  - Role of exercise duration on metabolic adaptations in working muscle to short
      term moderate-to-heavy aerobic-based cycle training.
AB  - This study aimed at investigating the relative roles of the duration versus
      intensity of exercise on the metabolic adaptations in vastus lateralis to short
      term (10 day) aerobic-based cycle training. Healthy males with a peak aerobic
      power (VO2 peak) of 46.0 +/- 2.0 ml kg(-1) min(-1) were assigned to either a 30
      min (n = 7) or a 60-min (n = 8) duration performed at two different intensities
      (with order randomly assigned), namely moderate (M) and heavy (H), corresponding
      to 70 and 86 % VO2 peak, respectively. No change (P > 0.05) in VO2 peak was
      observed regardless of the training program. Based on the metabolic responses to
      prolonged exercise (60 % VO2 peak), both M and H and 30 and 60 min protocols
      displayed less of a decrease (P < 0.05) in phosphocreatine (PCr) and glycogen
      (Glyc) and less of an increase (P < 0.05) in free adenosine diphosphate (ADPf),
      free adenosine monophosphate (AMPf), inosine monophosphate (IMP) and lactate
      (La). Training for 60 min compared with 30 min resulted in a greater protection
      (P < 0.05) of ADPf, AMPf, PCr and Glyc during exercise, effects that were not
      displayed between M and H. The reduction in both VO2 and RER (P < 0.05) observed
      during submaximal exercise did not depend on training program specifics. These
      findings indicate that in conjunction with our earlier study (Green et al., Eur J
      Appl Physiol, 2012b), a threshold exists for duration rather than intensity of
      aerobic exercise to induce a greater training impact in reducing metabolic
      strain.

PMID- 23543068
TI  - Effect of trunk extensor fatigue on the postural balance of elderly and young
      adults during unipodal task.
AB  - Muscle fatigue can influence the various mechanisms that regulate balance. Few
      studies have investigated the effects of trunk extensor muscle fatigue on
      postural control. The purpose of this study was to evaluate the impact of trunk
      extensor fatigue during a one-leg balance test in young and elderly adults, as
      well as to determine the time necessary to recover posture control after fatigue.
      A total of 36 subjects (18 elderly and 18 young adults) participated in the
      study. Subjects were tested on a force platform to assess the postural control
      parameters associated with center of pressure (COP) movements, before and after a
      fatiguing trunk extension-flexion exercise on a roman chair carried out to
      exhaustion. Post-fatigue effects and postural control recovery were investigated
      at different times in minutes (MIN): immediately post-fatigue (postIME), after 5
      (rec5MIN), 10 (rec10MIN), and 20 min (rec20MIN). Elderly subjects had greater
      sway (P < 0.05) than young adults in all COP parameters. In both groups, there
      was an increase in postIME sway compared with pre-fatigue values for all COP
      parameters. However, the differences were significant only for the COP velocity
      parameter, with more pronounced effects in young adults that did not return to
      pre-fatigue values at the end of rec20MIN. The present study demonstrated a
      significant effect of trunk extensor muscle fatigue on postural control, which
      was more evident in young adults than in the elderly.

PMID- 23543069
TI  - The physiological and biomechanical contributions of poling to roller ski
      skating.
AB  - Poling is considered to make a significant contribution to cross-country skiing
      with the skating technique. To better understand this contribution, the current
      investigation compared roller ski skating on a treadmill with the so-called G3
      skating technique with (G3-P) and without poling (G3-NP). Seven male elite skiers
      performed 5-min submaximal tests at 8, 12, and 15 km h(-1), as well as an
      incremental test to exhaustion with both techniques on a 5 % incline. Ventilatory
      variables were assessed by open-circuit indirect calorimetry and three
      dimensional kinematics analyzed using the Qualisys Pro Reflex system. G3-P was
      associated with approximately 15 % higher peak velocity and 10 % higher peak
      oxygen uptake than G3-NP in the incremental test (both P < 0.01). All ventilatory
      variables, as well as heart rate and blood lactate concentration were lower with
      G3-P as compared to G3-NP at 12 and 15 km h(-1) (all P < 0.01). Gross efficiency
      (i.e., the ratio of work rate to metabolic rate) at 12 km h(-1) was higher in G3
      P (14.9 %) than G3-NP (13.5 %) (P < 0.01). Moreover, with G3-P cycle time and
      length were both 30 % longer, with correspondingly reduced cycle rates (all P <
      0.01). In addition, the ski gliding and swing phases were longer and the angle
      between the skis smaller with G3-P (both P < 0.01), whereas the push-off time was
      independent of technique and velocity. Taken together, these results indicate
      that poling makes an important contribution to propulsion and velocity during ski
      skating, specifically by enhancing peak oxygen uptake, skiing efficiency and
      associated biomechanical variables.

PMID- 23543070
TI  - The Effects of Geometry on Skin Penetration and Failure of Polymer Microneedles.
AB  - Microneedles are small-scale devices that may be used for drug delivery and
      biosensing. In this study, the forces required for mechanical failure, the modes
      of mechanical failure, as well as the mechanisms for microneedle penetration into
      porcine skin were examined. Microneedles produced from the acrylate-based polymer
      e-Shell 200 using an indirect rapid prototyping approach involving two-photon
      polymerization and poly(dimethylsiloxane) micromolding were found to possess
      sufficient strength for penetration of porcine skin. The failure forces were an
      order of magnitude greater than the forces necessary for full insertion into the
      skin. Bending was the most common form of failure; an increasing aspect ratio and
      a decreasing tip diameter were associated with lower failure forces. Video
      captured during skin penetration revealed that microneedle penetration into the
      skin occurred by means of a series of insertions and not by means of a single
      insertion event. Images obtained during and after skin penetration confirmed
      microneedle penetration of skin as well as transdermal delivery of lucifer yellow
      dye. These findings shed insight into the mechanisms of microneedle penetration
      and failure, facilitating design improvements for polymer microneedles.

PMID- 23543071
TI  - Comparative Evaluation of the in-vitro Activity of Six beta-lactam/beta-lactamase
      Inhibitor Combinations against Gram Negative Bacilli.
AB  - BACKGROUND: The extensive use of the beta-lactam antibiotics in hospitals and in
      the community has created major resistance problems which has led to increased
      morbidity, mortality and healthcare costs. The use of the beta-lactamase
      inhibitors in combination with the beta-lactam antibiotics is currently the most
      successful strategy used for circumventing the resistance mechanisms. OBJECTIVE:
      To evaluate the in-vitro activity of six commercially available beta-lactam/beta
      lactamase inhibitor combinations against Gram Negative Bacilli (GNB). MATERIALS
      AND METHODS: A total of 384 non duplicate, consecutive, gram negative bacilli
      (278 Enterobacteriaceae and 106 non fermenters) isolated from various clinical
      samples were subjected to antimicrobial sensitivity testing by the Kirby-Bauer
      method. The following beta-lactam/beta-lactamase inhibitor combinations were
      tested: amoxycillin-clavulanic acid, ampicillin-sulbactam, cefoperazonesulbactam,
      piperacillin-tazobactam, cefepime-tazobactam and ticarcillin-clavulanic acid.
      RESULTS: Against the Enterobacteriacae, the sensitivity of Cefepime- tazobactam
      was 90. 64%, followed by Cefoperazone-sulbactam (84.89%) and Piperacillin -
      tazobactam (53.95 %). The sensitivity of the non fermenters was the highest for
      Cefepime- tazobactam (49.04%) and was least for Ampicillin-sulbactam and
      Amoxycillinclavulanic acid (4.71% each). Cefepime-tazobactam was sensitive for
      all the extended spectrum beta-lactamase (ESBL) isolates. CONCLUSION: Among the
      six beta-lactam/beta-lactamase inhibitor combinations tested, Cefepime-tazobactam
      exhibited the best in-vitro activity against the gram negative bacilli isolated
      at our centre.

PMID- 23543072
TI  - Transplacental transmission of Babesia equi (Theileria equi) from carrier mares
      to foals.
AB  - This article communicates the first per-acute and fatal clinical report of
      transplacental transmission of Theileria equi from carrier mothers to foals from
      Punjab, India. Two cases of equine piroplasmosis due to T. equi were diagnosed in
      neonatal foals borne to Throughbred mares. High degree of parasitemia with
      annular and maltese cross shaped parasites in erythrocytes was seen in both
      cases. Blood cellular changes revealed leucopenia and neutropenia with mild
      degenerative left shift. Anaemia was macrocytic normochromic type. Intense yellow
      discoloration of mucous membranes indicated jaundice. In areas endemic for equine
      piroplasmosis, jaundice in neonatal foal can be easily misdiagnosed as neonatal
      isoerythrolysis. Foals with post-partum jaundice should always be screened for
      equine piroplasmosis.

PMID- 23543073
TI  - Cloning, expression, and characterization of iron superoxide dismutase in
      Sonneratia alba, a highly salt tolerant mangrove tree.
AB  - In this study, a novel iron superoxide dismutase (FeSOD) gene from Sonneratia
      alba was cloned and then expressed in Escherichia coli Rosetta-gami, designated
      as SaFeSOD. The DNA sequence of SaFeSOD contained a 786-bp open reading frame
      which encodes a 261 amino-acid protein of 30.0 kDa. The 651-bp fragment coding
      for putative mature SaFeSOD was amplified and inserted into pET15b for
      expression. This recombinant SaFeSOD was subsequently isolated by Ni-trap column
      protein purification system. The apparent molecular mass of the purified enzyme
      was 25 kDa on SDS-PAGE. In comparison with FeSODs from other plant species, all
      iron-binding sites (His 27, His 80, Asp 164 and His 168) of SaFeSOD were
      conserved. SaFeSOD was found to have good pH stability in the pH range of 3.5-9.5
      at 25  degrees C after 1 h incubation and was relatively stable and showed 78 %
      activity when incubated in 50  degrees C for 1 h. Quantitative real-time PCR
      experiments demonstrated that SaFeSOD was expressed in leaf, stem, flower, fruit
      and root tissues with the highest expression in leaf tissues.

PMID- 23543074
TI  - C-terminal flanking peptide stabilized the catalytic domain of a recombinant
      Bacillus subtilis endo-beta-1, 4-glucanase.
AB  - Three proteins, Egl330, Egl326 and Egl325, which covered the catalytic domain of
      a Bacillus subtilis endo-beta-l, 4-glucanase were expressed in Escherichia coli
      and purified. Egl325 was a mutant of Egl330 with the peptide sequence Arg-Glu-Asn
      Ile-Arg deleted in the C-terminus and Egl326 was another mutant of Egl330 with
      the peptide sequence Glu-Asn-Ile-Arg deleted in the C-terminus. These three
      proteins displayed same optimal reaction pH and temperature. However, the thermal
      stability and pH stability of Egl326 and Egl325 were diminished compared to
      Egl330. Results of ultra violet scanning, circular dichroism and Trp fluorescence
      spectrometry showed that the absence of the short peptide at the C-terminus of
      Egl330 resulted in the destabilization of the catalytic domain through affecting
      the folding of the protein.

PMID- 23543075
TI  - Women Inmate Substance Abusers' Reactivity to Visual Alcohol, Cigarette,
      Marijuana, and Crack-Cocaine Cues: Approach and Avoidance as Separate Dimensions
      of Reactivity.
AB  - Despite the growing recognition for multidimensional assessments of cue-elicited
      craving, few studies have attempted to measure multiple response domains
      associated with craving. The present study evaluated the Ambivalence Model of
      Craving (Breiner et al., 1999; Stritzke et al., 2007) using a unique cue
      reactivity methodology designed to capture both the desire to use (approach
      inclination) and desire to not consume (avoidance inclination) in a clinical
      sample of incarcerated female substance abusers. Participants were 155
      incarcerated women who were participating in or waiting to begin participation in
      a nine-month drug treatment program. Results indicated that all four substance
      cue-types (alcohol, cigarette, marijuana, and crack cocaine) had good reliability
      and showed high specificity. Also, the validity of measuring approach and
      avoidance as separate dimensions was supported, as demonstrated by meaningful
      clinical distinctions between groups evincing different reactivity patterns and
      incremental prediction of avoidance inclinations on measures of stages of change
      readiness. Taken together, results continue to highlight the importance of
      measuring both approach and avoidance inclinations in the study of cue-elicited
      craving.

PMID- 23543076
TI  - Epidemiology and outcome analysis of children with traumatic out-of-hospital
      cardiac arrest compared to nontraumatic cardiac arrest.
AB  - PURPOSE: This study aimed to determine predictive factors for sustained return of
      spontaneous circulation (ROSC) in pediatric patients with traumatic out-of
      hospital cardiac arrest (OHCA) and compared to those with nontraumatic OHCA.
      METHODS: This was a retrospective prognostic study of children with OHCA
      presenting to the emergency department (ED) was conducted from 2005 to 2010.
      Related clinical factors that influenced sustained ROSC in traumatic OHCA
      patients were identified and compared to nontraumatic cases. Significant
      parameters in predicting sustained ROSC in traumatic OHCA children were also
      determined using multivariate logistic regression analysis, and etiologies of the
      ICU admissions were analyzed in patients with sustained ROSC. RESULTS: Among
      2,978 critically ill children admitted to the ED, 150 were pediatric OHCA
      patients, including 76 traumatic cases and 74 nontraumatic cases. Of children
      with OHCA, initial sustained ROSC was achieved in 51 cases (34.0 %), including 31
      traumatic cases and 20 of nontraumatic cases. Head and neck injuries were the
      majority of traumatic cases in the traumatic OHCA children, followed by abdominal
      injuries and chest injuries. However, abdominal injuries accounted for the
      highest rate to gain sustained ROSC, while chest injuries had the lowest rate for
      successful sustained ROSC. Significant factors associated with sustained ROSC in
      traumatic OHCA included initial cardiac rhythm (P < 0.05), the period from scene
      to hospital (P < 0.05), and the duration of in-hospital cardiopulmonary
      resuscitation (CPR) (P < 0.05). CONCLUSIONS: Significant factors related to
      sustained ROSC have been identified as initial cardiac rhythm, duration of in
      hospital CPR, and the period from scene to hospital. Head and neck injuries were
      the majority of traumatic cases and the prevention in head and neck trauma may
      play an important part in public health aspects.

PMID- 23543078
TI  - Development and evaluation of a video exercise program for locomotive syndrome in
      the elderly.
AB  - OBJECTIVES: To develop and evaluate an exercise program that the elderly could
      sustainably perform in the community or at home to recover from locomotive
      syndrome. METHODS: We produced 2 types of teaching media, video and pamphlet,
      describing 10 physical and mobility training exercises. The pilot study examined
      changes in pulse rate, percutaneous oxygen saturation (SpO2), and the Borg scale
      rating of perceived exertion in 20 elderly volunteers. Separately, 120 elderly
      subjects were recruited and divided into 3 groups according to the teaching
      medium (video, group V; pamphlet, group P; none, group C). Before and 3 months
      after the intervention, visual analog scale (VAS) scores of low back and knee
      pain, single-leg standing time, 6-m walking time, Roland-Morris Disability
      Questionnaire, Oswestry Disability Index, Short Form-8, and 25-question Geriatric
      Locomotive Function Scale were evaluated. RESULTS: Pulse-rate changes before and
      after exercise did not exceed 20 %, and SpO2 changes were within 4 points in all
      cases. The Borg scale ranged between 11 and 14. The intergroup comparison
      revealed the advantage of the video program in improving the VAS of low back
      pain, left-leg standing time, and 6-m walking time. CONCLUSION: A video exercise
      program can potentially aid recovery from locomotive syndrome in the elderly.

PMID- 23543077
TI  - Clinical manifestations of alpha-thalassemia.
AB  - alpha-Thalassemia mutations affect up to 5% of the world's population. The
      clinical spectrum ranges from an asymptomatic condition to a fatal in utero
      disease. Hemoglobin H disease results from mutations of three alpha-globin genes.
      Deletional forms result in a relatively mild anemia, whereas nondeletional
      mutations result in a moderate to severe disease characterized by ineffective
      erythropoiesis, recurrent transfusions, and growth delay. Hemosiderosis develops
      secondary to increased iron absorption, as well as transfusion burden. Hemoglobin
      Bart's hydrops fetalis is usually a fatal in utero disease caused by the absence
      of alpha genes. Population screening to identify at-risk couples is essential.
      Affected pregnancies result in severe fetal and maternal complications. Doppler
      ultrasonography with intrauterine transfusion therapy may improve the fetal
      prognosis but creates ethical challenges for the family and health providers.

PMID- 23543079
TI  - Clinical correlation of brachial artery flow-mediated dilation in patients with
      systemic sclerosis.
AB  - OBJECTIVE: To investigate the clinical significance of flow-mediated dilation
      (FMD) in systemic sclerosis (SSc). METHODS: Thirty-three SSc patients and 12
      healthy controls were studied. Ultrasound assessment of the brachial artery FMD
      was performed on all subjects. The results were expressed as the percentage of
      increase in brachial artery diameter following hyperemia. RESULTS: Limited
      cutaneous SSc (lcSSc) patients had significantly lower FMD values than healthy
      controls (5.3 +/- 2.7 versus 7.7 +/- 2.0 %, p < 0.05), while the values in
      diffuse cutaneous SSc (dcSSc) patients (6.7 +/- 4.0 %) were comparable to those
      in lcSSc patients and healthy controls. Although FMD values did not correlate
      with any clinical features in dcSSc patients, there was an inverse correlation
      between FMD values and disease duration in lcSSc patients (r = -0.64, p < 0.05).
      Furthermore, lcSSc patients with decreased FMD values showed significantly higher
      prevalence of digital ulcers and elevated right ventricular systolic pressure
      than those with normal values (for each; 75 versus 10 %, p < 0.05). CONCLUSION:
      The FMD values represent the severity of vascular damages, which progress along
      with disease duration and lead to digital ulcers and pulmonary arterial
      hypertension, in lcSSc patients.

PMID- 23543082
TI  - Management of thyroid carcinoma showing thymus-like differentiation (CASTLE)
      invading the trachea.
AB  - PURPOSE: To define the clinicopathological features and discuss the optimal
      management of carcinoma showing thymus-like differentiation (CASTLE). METHODS: We
      retrospectively analyzed six patients with CASTLE. RESULTS: The subjects
      comprised two men and four women (average age at initial diagnosis, 61 years,
      range 47-75 years). Preoperative biopsy yielded a correct diagnosis in two
      patients. Five patients underwent surgery and one was treated with radiation
      therapy alone. Four had extrathyroidal invasion and three had lymph node
      metastasis. During the clinical course, tracheal invasion was detected in five
      patients, the upper extent of the tumor being the lower half of the first
      tracheal ring. Two of these patients underwent tracheal sleeve resection. Two
      patients received postoperative radiotherapy for nodal metastasis, and one, after
      palliative surgery. The median follow-up period was 67 months (range 38-129).
      Recurrence was found 10 years post-therapy in the patient treated with radiation
      therapy only, resulting in death soon after. Although local recurrence was not
      found in the remaining five patients, new pulmonary metastases were diagnosed in
      the patient who underwent non-curative surgery. CONCLUSIONS: CASTLE can be
      diagnosed preoperatively by core needle biopsy and CD5 staining. Curative
      resection with neck dissection followed by radiotherapy can yield a good outcome.
      Larynx-sparing complete resection may be more feasible for CASTLE, even though it
      has a higher incidence of tracheal invasion than differentiated thyroid
      carcinoma.

PMID- 23543083
TI  - Prospective study comparing the new sclerotherapy and hemorrhoidectomy in terms
      of therapeutic outcomes at 4 years after the treatment.
AB  - PURPOSE: Recently, sclerotherapy using a new sclerosing agent (aluminum potassium
      sulfate and tannic acid) has become widespread in Japan as a treatment for
      hemorrhoids. In the present study, we investigated whether sclerotherapy or
      surgical therapy (hemorrhoidectomy) is superior in terms of the therapeutic
      outcomes at 4 years. METHODS: We sent a questionnaire on symptoms and the degree
      of satisfaction to patients who underwent sclerotherapy or hemorrhoidectomy for
      grade 3 or 4 hemorrhoids in 2007, and compared the two therapies based on the
      responses, with respect to superiority of the therapeutic outcomes at 4 years. To
      identify the factors affecting the symptom-free and satisfaction rates, the
      univariate and multivariate analyses were performed for the following seven
      parameters: age, sex, degree of hemorrhoids, presence of external hemorrhoids,
      past history of treatment for hemorrhoids, number of hemorrhoids treated and the
      type of treatment. RESULTS: Overall, 75 % of the patients (195/260) responded to
      the questionnaire. In this study, the symptom-free rates were 53 % (30/57
      patients) in the sclerotherapy group and 80 % (111/138 patients) in the
      hemorrhoidectomy group, and the satisfaction rates were 70 % (40/57 patients) in
      the sclerotherapy group and 88 % (121/138 patients) in the hemorrhoidectomy
      group. The results revealed that the type of treatment was the only factor
      affecting these two outcomes. CONCLUSIONS: Our results indicate that
      hemorrhoidectomy is superior to sclerotherapy. These findings may be useful in
      the treatment of hemorrhoid patients.

PMID- 23543084
TI  - XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms in esophageal cancer
      risk: a meta-analysis.
AB  - BACKGROUND: The X-ray repair cross-complementation group 1 (XRCC1) protein plays
      an important role in base excision repair. AIM: To elucidate the role of XRCC1
      Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all
      available studies were considered in the present meta-analysis. METHODS: Eligible
      studies were identified by searching several electronic databases for relevant
      reports published before June 2012. RESULTS: According to the inclusion criteria
      and exclusion criteria, a total of 21 eligible studies were included in the
      pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11
      described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis
      suggested that there was no evidence of significant association between XRCC1
      Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the
      stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal
      cancer, the results showed that Arg399Gln polymorphism was not associated with
      esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1
      Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His
      genotypes were not significantly associated with increased risk of EC. A similar
      negative association was maintained in dominant and recessive models. However,
      for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the
      variant genotype Trp/Trp had a significant increased risk of esophageal cancer
      (OR = 1.295, 95 % CI 1.053-1.591, P = 0.014). In addition, increased associations
      were found in recessive model (OR = 1.332, 95 % CI 1.093-1.624, P = 0.005).
      CONCLUSIONS: Our meta-analysis suggested that Arg194Trp Trp allele might act as a
      risk allele in its association with esophageal cancer.

PMID- 23543085
TI  - Association study of genetic variants in miRNAs in patients with inflammatory
      bowel disease: preliminary results.
AB  - BACKGROUND: Aberrant expression and structural alteration of miRNAs are
      considered to participate in inflammation and cancer development. It has been
      suggested that common single-nucleotide polymorphisms (SNPs) in miRNAs are
      associated with susceptibility to several human diseases. METHODS: In the present
      preliminary study we evaluated the associations of two SNPs (rs2910164 and
      rs11614913 in miR-146a and miR-196a2, respectively) with the risk of inflammatory
      bowel disease (IBD) in a Greek population. RESULTS: The rs2910164 and rs11614913
      SNPs were genotyped in 242 patients with Crohn's disease (CD), 210 patients with
      ulcerative colitis (UC) and 300 healthy individuals. No statistically significant
      differences were found in the genotype or allele distributions of the rs2910164
      SNP among UC and control subjects. However, significant differences were found in
      the genotype or allele distributions of the rs2910164 polymorphism among CD and
      control subjects (P < 0.0001 and P < 0.0001, respectively). Concerning the
      rs11614913, no statistically significant differences were found in the genotype
      or allele distributions among CD and control patients, whereas TT genotype and T
      allele seem to have a protective role against UC (P = 0.017 and P = 0.007,
      respectively). The presence of rs2910164 and rs11614913 SNPs did not influence
      disease phenotype. CONCLUSIONS: Our results demonstrate that the rs2910164
      polymorphism has a major role in genetic susceptibility to CD but not to UC,
      since the rs11614913 polymorphism had a protective role against UC, at least in
      the population studied here. Independent studies are needed to validate our
      findings in larger series and in patients of different ethnic origins.

PMID- 23543086
TI  - endoscopic papillary large-balloon dilatation in patients with Billroth II
      gastrectomy.

PMID- 23543087
TI  - A systematic review of SAPHO syndrome and inflammatory bowel disease association.
AB  - BACKGROUND: The association between inflammatory bowel disease (IBD) and
      synovitis, acne, pustulosis, hyperostosis, osteitis syndrome (SAPHO syndrome) was
      first reported in 1992. To date, only case reports and short series have been
      published. AIMS: The purpose of this study was to report new cases and
      systematically review the literature on this association. MATERIALS AND METHODS:
      All patients with concomitant diagnosis of SAPHO syndrome and IBD were identified
      from the databases of the rheumatology and gastroenterology departments of our
      institution. In addition, we systematically searched for published full articles
      in Medlars Online International Literature via PubMed. Relevant information of
      each positive match was collected and all authors were contacted for additional
      clinical data. RESULTS: Three patients sharing both SAPHO syndrome and IBD were
      identified among the 62 patients with SAPHO syndrome (4.8 % of the SAPHO cohort)
      and the 1,309 patients with IBD (0.2 % of the IBD cohort) from our hospital
      database. After a systematic review, a total of 39 reported patients with
      concomitant diagnosis of SAPHO syndrome and IBD were identified. There was a
      female predominance and most had Crohn's disease with colonic involvement.
      CONCLUSIONS: The association of SAPHO syndrome and IBD seems to be rare among IBD
      patients but not so among SAPHO patients. SAPHO could be underdiagnosed because
      of the similarity of its clinical manifestations and some more common
      extraintestinal manifestations or drug-related side effects in IBD.

PMID- 23543088
TI  - Is pyloric gland metaplasia in ileal pouch biopsies a marker for Crohn's disease?
AB  - BACKGROUND: Approximately 5-10 % of ulcerative colitis (UC) patients who undergo
      ileal pouch-anal anastomosis (IPAA) will develop postoperative complications such
      as refractory pouchitis or a change in diagnosis to Crohn's disease (CD).
      Serological markers and histologic aspects of the pouch such as pyloric gland
      metaplasia (PGM) have been associated with a risk for these complications.
      METHODS: Twenty-eight IPAA patients with either CD of the pouch or chronic
      pouchitis (cases) and 36 IPAA controls who experienced a normal postoperative
      course were originally consented. Of these 64 subjects, 22 cases and 17 controls
      had histopathologic and serologic data available and were subsequently enrolled.
      Demographic and clinical data were entered into a database, blood analyzed for
      serological markers (Prometheus Labs, San Diego, CA) and biopsies of the pouch
      and the afferent limb reviewed by two GI pathologists. RESULTS: Of the cases, 55
      % (12/22) had evidence of PGM in their pouch and/or small bowel biopsies, as
      compared to 12 % (2/17) of the controls (p = 0.006). Of 13 subjects with CD, 77 %
      (10/13) were found to have PGM versus subjects with chronic pouchitis in which 22
      % (2/9) were found to have PGM (p = 0.03). There was a trend of ASCA positivity
      (both IgG and IgA, p = 0.20) and of higher ASCA titer levels (p = 0.07) with
      postoperative complications. CONCLUSION: This study suggests that the presence of
      ileal pouch PGM is associated with postoperative complications and favors a
      diagnosis of CD over UC with chronic pouchitis.

PMID- 23543089
TI  - Revising the upper limit of normal for levels of serum alanine aminotransferase
      in a Middle Eastern population with normal liver histology.
AB  - BACKGROUND: Recently, the upper limits of normal (ULN) for alanine
      aminotransferase (ALT) has been recommended to be lowered to <= 30 U/l in men and
      <= 19 U/l in women. AIM: To evaluate the ALT concentrations in a healthy Middle
      Eastern population with biopsy-proven normal liver tissue. METHODS: ALT values
      were calculated from 175 consecutive Saudi potential living liver donors who
      underwent a liver biopsy as part of a stepwise pretransplant workup. RESULTS: The
      mean age of the 110 potential donors with normal liver histology was 27 +/- 6.2
      years for men and 38.6 +/- 7.1 years for women. The mean body mass index (BMI)
      levels were 23.0 +/- 3.5 kg/m(2) for men and 24.7 +/- 3.25 kg/m(2) for women, and
      the ALT levels were higher in male patients (22.6 +/- 9 vs. 16.4 U/l +/- 8, p
      value = 0.003). Multivariate linear regression showed that BMI and sex were
      independent variables that were positively associated with the levels of ALT (p <
      0.0001). Moreover, when we analyzed donors according to the Prati criteria, 63
      (36.0 %) of the individuals were classified into this subgroup. The mean ALT
      concentration was 12.9 U/l +/- 4.5 in women and 19.7 U/l +/- 6.9 in men, and
      these values were significantly lower than those obtained from subjects who did
      not fit the Prati criteria (19.4 U/l +/- 1.8, p = 0.04 for women and 29.0 U/l +/-
      12.1, p = <0.0001 for men). Thus, we calculated healthy ALT values of 33 IU/l for
      men and 22 IU/l for women. CONCLUSIONS: The ULN for ALT levels in Middle Eastern
      populations should be lowered, including separate values for males and females.
      Furthermore, metabolic parameters were shown to have a significant effect on ALT
      levels.

PMID- 23543090
TI  - A Study on the Correlation between Cord Blood Glucose Level and the Apgar Score.
AB  - INTRODUCTION: The study of the biochemical parameters of cord blood acts as a
      mirror, which usually reflects the neonatal status. The widely used system for
      the evaluation of a neonate is the Apgar score. There is no comprehensive
      published data which has established the association between the cord blood
      glucose level and the Apgar score. Similarly, there is also no well accepted
      reference range of the cord blood glucose level. OBJECTIVES: The main objectives
      of the present study was to ascertain any adverse effects of an abnormal cord
      blood glucose level on the neonatal status and to find out a standard reference
      level of glucose in cord blood. METHODS: The cord blood glucose estimation was
      done by using the glucose oxidase peroxidase method and the statistical analysis
      was performed by using the SPSS, version 16 software. RESULTS AND CONCLUSIONS: In
      the present study, the cord blood glucose level was found to have no correlation
      with the Apgar scores which were calculated at both one minute and five minutes
      after birth. It was also found that for the foetus to be free from any obvious
      complication, the cord blood glucose level had to be around 87 mg/dl. The
      fluctuations in the maternal glucose levels are weakly associated with the
      glucose level in the cord blood.

PMID- 23543091
TI  - The MU-opioid receptor and treatment response to naltrexone.
AB  - AIMS: To evaluate the pharmacogenetic evidence relating to the use of opioid
      antagonists (in particular naltrexone) in treating patients with alcohol abuse
      problems. METHODS: Narrative review of pre-clinical and clinical published
      research regarding genetic modulation of psychotropic effects produced by alcohol
      and the therapeutic effects of opioid antagonists. RESULTS: Alcohol activates
      brain reward pathways, leading to positive reinforcement of alcohol seeking and
      consumption. Thus, the underlying biological mechanisms may be targets for
      treatment, particularly in the early stages of addiction development. Alcohol
      reward is in part mediated by endogenous opioids. A single-nucleotide
      polymorphism (SNP) within the OPRM1 gene, A118G, leading to an amino acid change
      (Asn40Asp) in the extracellular portion of the receptor, has been implicated in
      alcoholism as well as in drug addiction, pain sensitivity and stress response,
      and in animal and human studies relates to the alcohol-dependent phenotype as
      well as to the treatment response to the u-opioid antagonist naltrexone.
      CONCLUSION: The effect size reported in naltrexone clinical studies is often
      small, which may be due to heterogeneity among patients. Pharmacogenetic
      approaches may help guide us in the search for the appropriate treatment optimal
      for one patient's need.

PMID- 23543092
TI  - Self-affirmation, intentions and alcohol consumption in students: a randomized
      exploratory trial.
AB  - AIMS: This study tests whether enhancing alcohol risk messages with self
      affirmation, the process of focusing on cherished aspects of oneself, increases
      intentions to reduce alcohol consumption and reduces actual alcohol consumption.
      It was also examined whether these effects differed by risk status as indicated
      by standard drinks consumed in an average week. METHODS: Participants (n = 121)
      were randomly allocated to a self-affirmation or matched control condition before
      viewing emotive graphic alcohol warning posters in a questionnaire-based study.
      RESULTS: There were significant increases in intentions to reduce alcohol
      consumption in self-affirmed participants, and these effects were stronger in
      participants with higher behavioural risk. Intentions in turn significantly
      predicted a reduction in self-reported alcohol consumption. CONCLUSIONS: These
      findings support the use of self-affirmation to enhance alcohol awareness
      campaigns, particularly in individuals with high behavioural risk.

PMID- 23543093
TI  - Genetic polymorphisms associated with exertional rhabdomyolysis.
AB  - Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals
      principally during strenuous exercise, athletic, and military training. Although
      many risk factors have been offered, it is unclear why some individuals develop
      ER when participating in comparable levels of physical exertion under identical
      environmental conditions and others do not. This study investigated possible
      genetic polymorphisms that might help explain ER. DNA samples derived from a
      laboratory-based study of persons who had never experienced an episode of ER
      (controls) and clinical ER cases referred for testing over the past several years
      were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes.
      These included angiotensin I converting enzyme (ACE), alpha-actinin-3 (ACTN3),
      creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B),
      interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate
      deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134
      controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %);
      the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were
      ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK
      C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM
      (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX
      genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of
      MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three
      distinct polymorphisms were associated with ER. Further work will be required to
      replicate these findings and determine the mechanism(s) whereby these variants
      might confer susceptibility.

PMID- 23543094
TI  - Testing for associations between loci and environmental gradients using latent
      factor mixed models.
AB  - Adaptation to local environments often occurs through natural selection acting on
      a large number of loci, each having a weak phenotypic effect. One way to detect
      these loci is to identify genetic polymorphisms that exhibit high correlation
      with environmental variables used as proxies for ecological pressures. Here, we
      propose new algorithms based on population genetics, ecological modeling, and
      statistical learning techniques to screen genomes for signatures of local
      adaptation. Implemented in the computer program "latent factor mixed model"
      (LFMM), these algorithms employ an approach in which population structure is
      introduced using unobserved variables. These fast and computationally efficient
      algorithms detect correlations between environmental and genetic variation while
      simultaneously inferring background levels of population structure. Comparing
      these new algorithms with related methods provides evidence that LFMM can
      efficiently estimate random effects due to population history and isolation-by
      distance patterns when computing gene-environment correlations, and decrease the
      number of false-positive associations in genome scans. We then apply these models
      to plant and human genetic data, identifying several genes with functions related
      to development that exhibit strong correlations with climatic gradients.

PMID- 23543095
TI  - The doctor is just a messenger: beliefs of ultraorthodox Jewish women in regard
      to breast cancer and screening.
AB  - Screenings for the early detection of breast cancer greatly improve survival
      odds. Studies of minority groups have shown lower attendance of screenings;
      however, these studies seldom focused on religious minorities. This study
      examines perceptions of cancer and cancer screening among healthy ultraorthodox
      women in order to gain insight about ways to promote screening. In this
      qualitative-phenomenological study of two focus groups, three main themes were
      found: faith in God; the Rabbi as a guide; one's relationship with the community.
      The study's findings point to the importance of studying the unique needs of
      members of certain religious groups. 

PMID- 23543096
TI  - Journal of Religion and Health. Editorial.

PMID- 23543097
TI  - Pseudotumor cerebri in a child treated with acitretin: a rare occurrence.
AB  - Pseudotumor cerebri (PTC) is a rare neurological disorder characterized by
      increased intracranial pressure in absence of any intra-cranial space-occupying
      lesion. It is mostly due to impairment of drainage of CSF from arachnoid villi.
      Clinically pseudotumor cerebri presents with headache, diplopia, nausea,
      vomiting, papilloedema and if treatment is delayed, may lead to blindness.
      Females of childbearing age group, endocrinal abnormalities and ingestion of
      certain drugs have been reported to be associated with pseudotumor cerebri.
      However, it's occurrence in relation to acitretin ingestion has not been reported
      on pubmed database. Here we present a case where significant temporal association
      of acitretin intake with PTC was found in a child who was being treated with this
      medication for recalcitrant pustular psoriasis. The case is reported for its
      rarity in occurrence and associated significant morbidity including visual loss
      if not diagnosed and treated immediately. According to Naranjo ADR Causality
      scale of adverse drug reaction, the association of PTC due to acitretin in our
      case was probable.

PMID- 23543098
TI  - Infantile neuroblastoma of the urinary bladder detected by hematuria.
AB  - Malignant tumors of the urinary bladder in infants are extremely rare.
      Rhabdomyosarcoma is the most likely tumor in this site, whereas neuroblastoma of
      the urinary bladder is exceedingly uncommon and is not listed as a differential
      diagnosis for tumors of this site. We present a case of neuroblastoma arising
      from the dome of the bladder wall, detected by hematuria. Only six cases of
      neuroblastoma originating from the bladder, including the present case have been
      reported. Of the cases, five arose from the dome of the bladder wall. In this
      report, the differential diagnosis of bladder tumors in children is discussed. A
      diagnosis of neuroblastoma should be taken into consideration, especially in the
      case of tumors arising from the dome of the bladder wall despite an uncommon
      location.

PMID- 23543099
TI  - Totally extraperitoneal inguinal hernia repair in patients on antithrombotic
      therapy: a retrospective analysis.
AB  - This report addresses whether it is safe to perform totally extraperitoneal (TEP)
      inguinal hernia repair for patients taking antithrombotic agents. Between January
      2011 and June 2012, 77 patients (70 men, 7 women) underwent TEP repair at Osaka
      Police Hospital, 22 (28.6 %) of whom had been treated with antithrombotic drugs
      preoperatively. Warfarin was stopped at least 3 days preoperatively and
      antiplatelet drugs were stopped at least 7 days preoperatively. Standard bridging
      intravenous heparin therapy was used according to the operative risk of each
      patient. The mean operative time, intraoperative bleeding, postoperative
      complications, and length of hospital stay did not differ significantly between
      these patients and a control group, although the patients on antithrombotic
      therapy were significantly older with higher surgical risk. No major
      complications or recurrence developed in either group. Our TEP repair method and
      bridging heparin therapy seem to be safe and feasible for minimizing
      postoperative complications.

PMID- 23543100
TI  - Failure by congestion of pedicled and free flaps for reconstruction of lower
      limbs after trauma: the role of negative-pressure wound therapy.
AB  - Lower limb reconstruction with pedicled or free flaps can be commonly compromised
      by venous insufficiency. This complication often leads to partial/complete flap
      necrosis and increases the risk of superinfection. Negative-pressure wound
      therapy (NPWT) is known to increase local blood flow, decrease edema, promote
      tissue granulation, and reduce the likelihood of soft tissue infection. This
      study aims to evaluate the effectiveness of NPWT in the treatment of congested
      pedicled and free flaps of the lower limb after reconstructions in lower limb
      traumas. A retrospective analysis was performed on four congested (pedicled and
      free) flaps on the lower limbs. NPWT was applied in all cases after partial flap
      debridement. NPWT was able to improve and resolve tissue edema and venous
      insufficiency, avoid further flap necrosis, and promote granulation. On NPWT
      removal, a split-thickness skin graft was applied on the wound, achieving
      complete and uneventful healing. NPWT is a useful instrument in managing flaps
      affected by venous insufficiency in lower limb reconstruction, although larger
      studies are necessary to better define the effectiveness and indications of NPWT
      in this setting. 

PMID- 23543101
TI  - Demonstration of estrogen receptor alpha protein in glutamatergic (vesicular
      glutamate transporter 2 immunoreactive) neurons of the female rat hypothalamus
      and amygdala using double-label immunocytochemistry.
AB  - By means of double-label immunocytochemistry, authors studied the presence of
      estrogen receptor alpha (ER-alpha) protein in vesicular glutamate transporter 2
      (VGluT2) protein-immunoreactive neurons in the female rat hypothalamus and
      amygdala. They examined colocalization of the 2 immunoreactive proteins in
      structures in which they found a significant overlap in the localization of the
      distribution of ER-alpha- and VGluT2-immunopositive nerve cells, namely in the
      medial preoptic area, the ventral subdivision of the ventromedial hypothalamic
      nucleus, and the medial amygdaloid nucleus. In the medial preoptic area, only
      2.74 % of ER-alpha-immunoreactive neurons were VGluT2 positive, and conversely, 5
      % of VGluT2-immunoreactive neurons contained ER-alpha immunofluorescent labeling.
      Highest degree of colocalization was detected in the ventral subdivision of the
      ventromedial hypothalamic nucleus, where 22.81 % of the ER-alpha-immunopositive
      neurons were VGluT2 immunoreactive and 37.14 % of the VGluT2-immunolabeled
      neurons contained ER-alpha-positive nucleus. In the medial amygdaloid nucleus,
      15.38 % of the ER-alpha and 18.1 % of the VGluT2-immunoreactive neurons were
      double labeled. The colocalizations suggest that glutamatergic (VGluT2 protein
      immunoreactive) neurons are involved in the mediation of the action of estrogen
      on the rat brain.

PMID- 23543102
TI  - Lateralized effects of prefrontal repetitive transcranial magnetic stimulation on
      emotional working memory.
AB  - Little is known about the neural correlates underlying the integration of working
      memory and emotion processing. We investigated the effects of low-frequency
      repetitive transcranial magnetic stimulation (rTMS) applied over the left or
      right dorsolateral prefrontal cortex (DLPFC) on emotional working memory. In a
      sham-controlled crossover design, participants performed an emotional 3-back task
      (EMOBACK) at baseline and after stimulation (1 Hz, 15 min, 110 % of the resting
      motor threshold) in two subsequent sessions. Stimuli were words assigned to the
      distinct emotion categories fear and anger as well as neutral words. We found
      lateralized rTMS effects in the EMOBACK task accuracy for fear-related words,
      with enhanced performance after rTMS applied over the right DLPFC and impaired
      performance after rTMS applied over the left DLPFC. No significant stimulation
      effect could be found for anger-related and neutral words. Our findings are the
      first to demonstrate a causal role of the right DLPFC in working memory for
      negative, withdrawal-related words and provide further support for a hemispheric
      lateralization of emotion processing.

PMID- 23543103
TI  - The impact of low-frequency stimulation of subthalamic region on self-generated
      isometric contraction in patients with Parkinson's disease.
AB  - Growing evidence suggests that spontaneous oscillatory low-frequency
      synchronization in the subthalamic nuclei (STN) may modulate motor performance in
      patients with Parkinson's disease (PD). To explore this in more detail, 15 PD
      patients chronically implanted with deep brain stimulation (DBS) electrodes in
      both STN were stimulated bilaterally at 5, 10, 20, 50 and 130 Hz and the effects
      of the DBS on self-initiated isometric elbow flexion (FLEX) and finger pinch
      (PINCH) were compared to performance without DBS. Baseline performance was very
      much impaired. Peak force was significantly greater during 130 and 10 Hz
      stimulation when compared to no stimulation in both tasks. Cumulative sums of the
      changes in mean rising force and peak force in the two tasks upon stimulation at
      10 and 20 Hz demonstrated that patients improved their performance on
      stimulation, except for those with the best performance off stimulation who
      deteriorated with stimulation at 20 Hz. Thus, no effect was detected with 20 Hz
      stimulation at the group level. The current study highlights the need to consider
      the baseline performance of a subject in a given task when determining the
      effects of low-frequency STN stimulation in PD patients. It also demonstrates
      that stimulation at 10 Hz can improve motor function in subjects with poor
      baseline function.

PMID- 23543104
TI  - Mirror visual feedback can induce motor learning in patients with callosal
      disconnection.
AB  - Mirror therapy using mirror visual feedback (MVF) has been applied to the stroke
      rehabilitation of hemiparesis. One possible mechanism of mirror therapy is the
      functional interhemispheric connectivity between sensorimotor areas via corpus
      callosum. To test this hypothesis, we investigated the MVF-induced motor learning
      in 2 patients with callosal disconnection. Callosal connection in patients was
      evaluated by clinical measures and the interhemispheric inhibition (IHI) using
      transcranial magnetic stimulation. Both patients suffered from somatosensory
      cognitive disconnection, and one showed the loss of IHI. Motor training with MVF
      significantly improved the motor behavior of both patients. Extending our
      previous study, the results of callosal patients suggested that the visual
      feedback through a mirror might play the crucial important role for the
      improvement of motor performance, rather than interhemispheric interaction via
      corpus callosum.

PMID- 23543105
TI  - Action co-representation and social exclusion.
AB  - Humans are thought to be able to form shared representations, considered a
      keystone of social cognition. However, whether and to what extent such
      representations are social in nature is still open for debate. In the present
      study, we address the question of whether action co-representation can be
      modulated by social attitudes, such as judgments about one's own social status.
      Two groups of participants performed an Interactive Simon task after the
      experimental induction of a feeling of social inclusion or exclusion (ostracism)
      by means of a virtual ball tossing game. Results showed a compatibility effect in
      included, but not in excluded participants. This indicates that judgments about
      one's own social status modulate action co-representation. We suggest that this
      modulation may occur by way of a redirection of one's attentional focus away from
      others when one experiences social exclusion. This is a far-reaching issue given
      the increasing need for integration in modern society. Indeed, if integration
      fails, modern society fails also.

PMID- 23543106
TI  - Violating the main sequence: asymmetries in saccadic peak velocities for saccades
      into the temporal versus nasal hemifields.
AB  - Saccadic peak velocities during monocular and binocular presentation were tested.
      While the main sequence linear increase in peak velocities as a function of
      saccade amplitude is well documented, our results provide demonstrations of
      violations of the main sequence. Peak velocities during monocular presentation
      were considerably higher toward temporal than nasal stimuli. This nasal-temporal
      asymmetry (NTA) was not explained by amplitude differences and was most
      pronounced for the lowest amplitudes tested, decreasing with increased amplitude.
      Under binocular presentation, this NTA was much smaller. While the exact reasons
      for this difference in peak velocities between hemifields are unclear at present,
      we propose that anatomical NTAs result in stronger signals from the nasal, than
      temporal retina leading to higher peak velocities into the temporal visual
      hemifield. NTAs in peak velocity are consistent with NTAs in attentional choice
      and in attentional function, which might also be explained by anatomical NTA.

PMID- 23543107
TI  - Effects of dorsomedial medullary 5-HT2 receptor antagonism on initial ventilatory
      airway responses to hypercapnic hypoxia in mice.
AB  - The anatomical factors involved in upper airway closure of obstructive sleep
      apnea (OSA) have been established. However, the mechanisms of repetitive OSA are
      not well understood. We found that dorsomedial medullary 5-HT2 receptor activity
      is compensated for by hypercapnia and elicits the immediate onset of
      poikilocapnic hypoxic ventilatory airway responses. Therefore, the aim of this
      study was to test the hypothesis that hypercapnia compensates for the immediate
      onset of poikilocapnic hypoxic ventilatory airway responses induced by
      dorsomedial medullary 5-HT2 receptors. Adult male mice (C57BL/6N) were
      intraperitoneally anesthetized with pentobarbital sodium. Microdialysis probes
      were inserted into the dorsomedial medulla oblongata of the mice. The mice were
      placed in a double-chamber plethysmograph and were allowed to acclimatize and
      recover from anesthesia. Mice were then exposed to hypercapnic hypoxic gases (7 %
      O2/5 % CO2 in N2) with or without 5-HT2-antagonist (10(-5) M LY-53857) perfusion.
      Respiratory curves through the head and body chambers were recorded to measure
      ventilatory airway variables. Extracellular fluid was collected every 5 min for
      HPLC analysis of 5-HT concentration. Hypercapnic hypoxia elicited neither delayed
      onset of ventilatory augmentation nor immediate airway narrowing with dorsomedial
      medullary 5-HT2 antagonism. Hypoxic polypnea was shifted downward. The increases
      in dorsomedial medullary 5-HT release and ventilatory volume were not affected
      with or without 5-HT2 activity. In conclusion, the onset of poikilocapnic hypoxic
      ventilatory airway responses mediated via dorsomedial medullary 5-HT2 activity is
      compensated for by hypercapnia. Maintenance of PCO2 level and CO2 responsiveness,
      especially with lowered 5-HT2 activity, may be important for preventing
      repetitive OSA. 

PMID- 23543108
TI  - A threshold level of oxalate oxidase transgene expression reduces Cryphonectria
      parasitica-induced necrosis in a transgenic American chestnut (Castanea dentata)
      leaf bioassay.
AB  - American chestnut (Castanea dentata) was transformed with a wheat oxalate oxidase
      (oxo) gene in an effort to degrade the oxalic acid (OA) secreted by the fungus
      Cryphonectria parasitica, thus decreasing its virulence. Expression of OxO was
      examined under two promoters: a strong constitutive promoter, CaMV 35S, and a
      predominantly vascular promoter, VspB. Oxo gene transcription was quantified by
      RT-qPCR. Relative expression of OxO varied approximately 200 fold among events
      produced with the 35S-OxO. The lowest 35S-OxO event expressed approximately 3,000
      fold higher than the highest VspB-OxO event. This was potentially due to the
      tissue-specific nature of the VspB-controlled expression, the strength of the
      CaMV 35S constitutive promoter, or position effects. Leaf assays measuring
      necrotic lesion length were conducted to better understand the relationship
      between OxO expression level and the blight fungus in planta. A threshold
      response was observed between the OxO expression level and the C. parasitica
      lesion length. Five events of the 35S-OxO line showed significantly reduced
      lesion length compared to the blight-susceptible American chestnut. More
      importantly, the lesion length in these five events was reduced to the same level
      as the blight-resistant Chinese chestnut, C. mollissima. This is the first report
      on enhanced pathogen resistance in transgenic American chestnut. 

PMID- 23543109
TI  - Phase I study of tanespimycin in combination with bortezomib in patients with
      advanced solid malignancies.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) and characterize the dose
      limiting toxicities (DLT) of tanespimycin when given in combination with
      bortezomib. EXPERIMENTAL DESIGN: Phase I dose-escalating trial using a standard
      cohort "3+3" design performed in patients with advanced solid tumors. Patients
      were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle
      (days 1, 4, 8, 11 every 21 days). RESULTS: Seventeen patients were enrolled in
      this study, fifteen were evaluable for toxicity, and nine patients were evaluable
      for tumor response. The MTD was 250 mg/m(2) of tanespimycin and 1.0 mg/m(2) of
      bortezomib when used in combination. DLTs of abdominal pain (13 %), complete
      atrioventricular block (7 %), fatigue (7 %), encephalopathy (7 %), anorexia (7
      %), hyponatremia (7 %), hypoxia (7 %), and acidosis (7 %) were observed. There
      were no objective responses. One patient had stable disease. CONCLUSIONS: The
      recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m(2) and
      1.0 mg/m(2), respectively, on days 1, 4, 8 and 11 of a 21 day cycle.

PMID- 23543110
TI  - Identification of genes differentially expressed in ectomycorrhizal roots during
      the Pinus pinaster-Laccaria bicolor interaction.
AB  - Ectomycorrhizal associations are of major ecological importance in temperate and
      boreal forests. The development of a functional ectomycorrhiza requires many
      genetic and biochemical changes. In this study, suppressive subtraction
      hybridization was used to identify differentially expressed genes in the roots of
      maritime pine (Pinus pinaster Aiton) inoculated with Laccaria bicolor, a
      mycorrhizal fungus. A total number of 200 unigenes were identified as being
      differentially regulated in maritime pine roots during the development of
      mycorrhiza. These unigenes were classified into 10 categories according to the
      function of their homologues in the GenBank database. Approximately, 40 % of the
      differentially expressed transcripts were genes that coded for unknown proteins
      in the databases or that had no homology to known genes. A group of these
      differentially expressed genes was selected to validate the results using
      quantitative real-time PCR. The transcript levels of the representative genes
      were compared between the non-inoculated and inoculated plants at 1, 5, 15 and 30
      days after inoculation. The observed expression patterns indicate (1) changes in
      the composition of the wall cell, (2) tight regulation of defence genes during
      the development of mycorrhiza and (3) changes in carbon and nitrogen metabolism.
      Ammonium excess or deficiency dramatically affected the stability of
      ectomycorrhiza and altered gene expression in maritime pine roots.

PMID- 23543112
TI  - The relationship between forgiveness and borderline personality symptomatology.
AB  - The relationship between forgiveness and borderline personality symptomatology
      has been rarely studied. Using a consecutive cross-sectional sample of 307
      internal medicine outpatients and a survey methodology, we examined correlations
      between the Forgiveness Scale and borderline personality symptomatology as
      measured by the borderline personality disorder scale of the Personality
      Diagnostic Questionnaire-4 and the Self-Harm Inventory. Numerous forgiveness
      subscales as well as the composite Forgiveness Scale score demonstrated
      statistically significant relationships with both measures for borderline
      personality symptomatology, such that individuals with this personality pathology
      demonstrated lower scores on these forgiveness subscales. Findings indicate that
      among individuals with borderline personality symptomatology, there are numerous
      aspects of forgiveness that are significantly lower than in individuals without
      this symptomatology. 

PMID- 23543111
TI  - Use of a support vector machine for categorizing free-text notes: assessment of
      accuracy across two institutions.
AB  - BACKGROUND: Electronic health record (EHR) users must regularly review large
      amounts of data in order to make informed clinical decisions, and such review is
      time-consuming and often overwhelming. Technologies like automated summarization
      tools, EHR search engines and natural language processing have been shown to help
      clinicians manage this information. OBJECTIVE: To develop a support vector
      machine (SVM)-based system for identifying EHR progress notes pertaining to
      diabetes, and to validate it at two institutions. MATERIALS AND METHODS: We
      retrieved 2000 EHR progress notes from patients with diabetes at the Brigham and
      Women's Hospital (1000 for training and 1000 for testing) and another 1000 notes
      from the University of Texas Physicians (for validation). We manually annotated
      all notes and trained a SVM using a bag of words approach. We then used the SVM
      on the testing and validation sets and evaluated its performance with the area
      under the curve (AUC) and F statistics. RESULTS: The model accurately identified
      diabetes-related notes in both the Brigham and Women's Hospital testing set
      (AUC=0.956, F=0.934) and the external University of Texas Faculty Physicians
      validation set (AUC=0.947, F=0.935). DISCUSSION: Overall, the model we developed
      was quite accurate. Furthermore, it generalized, without loss of accuracy, to
      another institution with a different EHR and a distinct patient and provider
      population. CONCLUSIONS: It is possible to use a SVM-based classifier to identify
      EHR progress notes pertaining to diabetes, and the model generalizes well.

PMID- 23543113
TI  - Comparing outcome of patients with coronary artery disease and dilated
      cardiomyopathy in ICD and CRT recipients: data from the German DEVICE-registry.
AB  - AIMS: The purpose of this study was to evaluate whether there are differences in
      use and outcome of implantable cardioverter defibrillator (ICD) therapy with or
      without cardiac resynchronization therapy (CRT) between patients with underlying
      coronary artery disease (CAD) and non-ischemic dilated cardiomyopathy (DCM).
      METHODS: A total of 2,263 consecutive patients from 44 German centers who
      underwent new ICD or CRT implantation between March 2007 and April 2010 were
      enrolled in the German DEVICE registry. Patients were followed for at least 1
      year. RESULTS: Of 1,621 patients who received an ICD, 1,202 (74.2%) had CAD and
      419 (25.8%) suffered from DCM. Patients who received CRT (n = 642) had CAD in
      52.2% and DCM in 47.8%. The vast majority received CRT with ICD backup (CRT-D,
      95%). In both ICD and CRT groups, CAD patients were older and more often male. LV
      ejection fraction in ICD patients with CAD was significantly higher than in DCM
      patients. Heart failure classification and history of atrial fibrillation were
      similar in CAD and DCM in CRT patients. There was no significant difference in
      mortality and first ICD shock delivery between CAD and DCM after 1 year of follow
      up. Heart failure symptoms showed significant improvement in CRT patients
      irrespective of the underlying disease. CONCLUSION: ICD and CRT patients in the
      DEVICE registry showed similar short-term outcome irrespective of their
      underlying disease etiology. Except older age and preponderance of males,
      clinical characteristics, device selection and outcome of ICD or CRT patients in
      the German DEVICE registry are comparable with patients from randomized trials.

PMID- 23543114
TI  - Role of serotonin 5-HT2A receptors in the development of cardiac hypertrophy in
      response to aortic constriction in mice.
AB  - Serotonin, in addition to its fundamental role as a neurotransmitter, plays a
      critical role in the cardiovascular system, where it is thought to be involved in
      the development of cardiac hypertrophy and failure. Indeed, we recently found
      that mice with deletion of monoamine oxidase A had enhanced levels of blood and
      cardiac 5-HT, which contributed to exacerbation of hypertrophy in a model of
      experimental pressure overload. 5-HT2A receptors are expressed in the heart and
      mediate a hypertrophic response to 5-HT in cardiac cells. However, their role in
      cardiac remodeling in vivo and the signaling pathways associated are not well
      understood. In the present study, we evaluated the effect of a selective 5-HT2A
      receptor antagonist, M100907, on the development of cardiac hypertrophy induced
      by transverse aortic constriction (TAC). Cardiac 5-HT2A receptor expression was
      transiently increased after TAC, and was recapitulated in cardiomyocytes, as
      observed with 5-HT2A in situ labeling by immunohistochemistry. Selective blockade
      of 5-HT2A receptors prevented the development of cardiac hypertrophy, as measured
      by echocardiography, cardiomyocyte area and heart weight-to-body weight ratio.
      Interestingly, activation of calmodulin kinase (CamKII), which is a core
      mechanism in cardiac hypertrophy, was reduced in cardiac samples from M100907
      treated TAC mice compared to vehicle-treated mice. In addition, phosphorylation
      of histone deacetylase 4 (HDAC4), a downstream partner of CamKII was
      significantly diminished in M100907-treated TAC mice. Thus, our results show that
      selective blockade of 5-HT2A receptors has beneficial effect in the development
      of cardiac hypertrophy through inhibition of the CamKII/HDAC4 pathway.

PMID- 23543115
TI  - Functions of the Hha and YdgT proteins in transcriptional silencing by the
      nucleoid proteins, H-NS and StpA, in Escherichia coli.
AB  - The Hha and YdgT proteins are suggested to modulate the expression of
      horizontally acquired genes by interacting with H-NS and StpA, which play central
      roles in the transcriptional silencing of such genes. However, it is also
      possible that Hha/YdgT repress gene expression independently of H-NS/StpA, as we
      have not fully understood the molecular mechanism through which Hha/YdgT modulate
      H-NS/StpA activity. To gain further insight into the basic functions of Hha/YdgT,
      we analysed the impact of hha/ydgT double inactivation on the transcriptome
      profile of Escherichia coli K-12, and compared the effects with that of hns/stpA
      double inactivation. In addition, we examined the effects of hha/ydgT
      inactivation on the chromosomal binding of H-NS, and conversely the effects of
      hns/stpA inactivation on the chromosomal binding of Hha. Our results demonstrated
      that the chromosomal binding of Hha requires H-NS/StpA, and is necessary for the
      repression of a subset of genes in the H-NS/StpA regulon. Furthermore, the
      distribution of H-NS binding around Hha/YdgT-dependent and -independent genes
      suggests that Hha/YdgT proteins modulate formation of the H-NS/StpA-DNA complex.

PMID- 23543116
TI  - Development and characterization of cDNA resources for the common marmoset: one
      of the experimental primate models.
AB  - The common marmoset is a new world monkey, which has become a valuable
      experimental animal for biomedical research. This study developed cDNA libraries
      for the common marmoset from five different tissues. A total of 290 426 high
      quality EST sequences were obtained, where 251 587 sequences (86.5%) had homology
      (1E(-100)) with the Refseqs of six different primate species, including human and
      marmoset. In parallel, 270 673 sequences (93.2%) were aligned to the human
      genome. When 247 090 sequences were assembled into 17 232 contigs, most of the
      sequences (218 857 or 15 089 contigs) were located in exonic regions, indicating
      that these genes are expressed in human and marmoset. The other 5578 sequences
      (or 808 contigs) mapping to the human genome were not located in exonic regions,
      suggesting that they are not expressed in human. Furthermore, a different set of
      118 potential coding sequences were not similar to any Refseqs in any species,
      and, thus, may represent unknown genes. The cDNA libraries developed in this
      study are available through RIKEN Bio Resource Center. A Web server for the
      marmoset cDNAs is available at http://marmoset.nig.ac.jp/index.html, where each
      marmoset EST sequence has been annotated by reference to the human genome. These
      new libraries will be a useful genetic resource to facilitate research in the
      common marmoset.

PMID- 23543117
TI  - Socioeconomic inequalities in adult obesity risk in Canada: trends and
      decomposition analyses.
AB  - This study examines trends in socioeconomic-related inequalities in obesity risk
      among Canadian adults (aged 18-65 years) from 2000 to 2010 using five nationally
      representative Canadian Community Health Surveys (CCHSs). We employed the
      concentration index (C) to quantify the socioeconomic inequalities in obesity
      risk across different demographic groups and geographic regions in each survey
      period. A decomposition analysis of inequality is performed to determine factors
      that lie behind income-related inequality in obesity risk. Although declining
      over time, the results show that there exists income-related inequality in
      obesity risk in Canada. The estimated Cs for men indicate that obesity is
      concentrated among the rich and its trend is increasing over time. The findings,
      however, suggest that obesity is more prevalent among economically disadvantaged
      women. While we found that obesity is mainly concentrated among the poor in the
      Atlantic Provinces, the degree of socioeconomic related inequality in obesity
      risk is increasing in these provinces. The results for Alberta showed that
      obesity is concentrated among the better-off individuals. The decomposition
      analysis suggests that factors such as demographics, income, immigration,
      education, drinking habits, and physical activity are the key factors explaining
      income-related inequality in obesity risk in Canada. Our empirical findings
      suggest that, in order to combat the obesity epidemic, health policies should
      focus on poorer females and economically well-off males. 

PMID- 23543120
TI  - INTERACTIVE VISUALIZATION OF PROBABILITY AND CUMULATIVE DENSITY FUNCTIONS.
AB  - The probability density function (PDF), and its corresponding cumulative density
      function (CDF), provide direct statistical insight into the characterization of a
      random process or field. Typically displayed as a histogram, one can infer
      probabilities of the occurrence of particular events. When examining a field over
      some two-dimensional domain in which at each point a PDF of the function values
      is available, it is challenging to assess the global (stochastic) features
      present within the field. In this paper, we present a visualization system that
      allows the user to examine two-dimensional data sets in which PDF (or CDF)
      information is available at any position within the domain. The tool provides a
      contour display showing the normed difference between the PDFs and an ansatz PDF
      selected by the user and, furthermore, allows the user to interactively examine
      the PDF at any particular position. Canonical examples of the tool are provided
      to help guide the reader into the mapping of stochastic information to visual
      cues along with a description of the use of the tool for examining data generated
      from an uncertainty quantification exercise accomplished within the field of
      electrophysiology.

PMID- 23543119
TI  - Constraints and challenges of meeting the water requirements of livestock in
      Ethiopia: cases of Lume and Siraro districts.
AB  - Compared to the total water use in livestock production systems, water for
      livestock drinking is small in amount but is an important requirement for health
      and productivity of animals. This study was carried out to assess constraints and
      challenges of meeting drinking water requirements of livestock in rural mixed
      smallholder crop-livestock farming districts in the Ethiopian Rift Valley area.
      Data was collected by individual interviews with randomly selected respondents
      and farmer group discussions. Farmers ranked feed and water scarcity as the two
      most important constraints for livestock husbandry, although the ranking order
      differed between districts and villages. Poor quality water was a concern for the
      communities in proximity to urban settlements or industrial establishments. Water
      provision for livestock was challenging during the dry season, since alternative
      water sources dried up or were polluted. Though rainwater harvesting by dugout
      constructions was practiced to cope with water scarcity, farmers indicated that
      mismanagement of the harvested water was posing health risks on both livestock
      and people. A sustainable water provision for livestock in the area, thus,
      depends on use of different water sources (intermittent or perennial) that should
      be properly managed. Industrial establishments should adopt an environment
      friendly production to minimize pollution of water resources used for livestock
      consumption. Technical support to farmers is required in proper design and use of
      existing rainwater harvesting systems. Further investigations are recommended on
      effect of poor quality water (perceived by farmers) on performance of livestock. 

PMID- 23543118
TI  - Dietary fibre and cardiovascular disease mortality in the UK Women's Cohort
      Study.
AB  - Dietary fibre has been associated with improvements in key risk factors for
      cardiovascular disease (CVD). Prior research has focussed more on CVD development
      in men and our aim was therefore to explore the association between dietary fibre
      intake and CVD mortality using data from the United Kingdom Women's Cohort Study
      (UKWCS). Dietary fibre intake from 31,036 women was calculated both as non-starch
      polysaccharide (NSP) and using the Association of Official Analytical Chemist
      (AOAC) method from food-frequency questionnaires. Participants were free from
      history of CVD at baseline and mean age at recruitment was 51.8 years (standard
      deviation 9.2). Mortality records for participants were linked from national
      registry data and 258 fatal CVD cases [130 stroke, 128 coronary heart disease
      (CHD)] were observed over an average follow-up period of 14.3 years. Total
      dietary fibre (NSP/AOAC) and fibre from different food sources were not
      associated with fatal CHD, stroke or CVD risk in the full sample. For every 6
      g/day increase in NSP, the hazard ratio (HR) was 0.91 (95 % confidence interval
      (CI) 0.76-1.08) or for every 11 g/day increase in fibre assessed as AOAC, the HR
      was 0.92 (95 % CI 0.80-1.05). Sensitivity analyses suggest a possible protective
      association for cereal sources of fibre on fatal stroke risk in overweight women,
      HR 0.80 (95 % CI 0.65-0.93) p < 0.01. In the UKWCS, a sample of health-conscious
      women, greater dietary fibre intake may confer no additional cardiovascular
      benefit, in terms of mortality, but may contribute to lower fatal stroke risk in
      some subgroups such as overweight women.

PMID- 23543121
TI  - Bayesian gamma frailty models for survival data with semi-competing risks and
      treatment switching.
AB  - Motivated from a colorectal cancer study, we propose a class of frailty semi
      competing risks survival models to account for the dependence between disease
      progression time, survival time, and treatment switching. Properties of the
      proposed models are examined and an efficient Gibbs sampling algorithm using the
      collapsed Gibbs technique is developed. A Bayesian procedure for assessing the
      treatment effect is also proposed. The deviance information criterion (DIC) with
      an appropriate deviance function and Logarithm of the pseudomarginal likelihood
      (LPML) are constructed for model comparison. A simulation study is conducted to
      examine the empirical performance of DIC and LPML and as well as the posterior
      estimates. The proposed method is further applied to analyze data from a
      colorectal cancer study. 

PMID- 23543122
TI  - A hairy cell leukaemia variant - a rare case report.
AB  - The aim of the article is to present a rare case of Hairy cell leukaemia variant
      (HCl-V) which is a distinct clinico-pathological entity with intermediate
      features between classical HCl (HCl-C) and B-cell prolymphocytic leukaemia. It is
      an uncommon disorder accounting for approximately 0.4% of chronic lymphoid
      malignancies and 10% of all HCl cases. A 58 year old woman presented with pain
      abdomen and loss of weight. On examination she had massive splenomegaly.
      Peripheral smear was reported as chronic lymphoproliferative disorder (? Hairy
      cell leukemia or splenic lymphoma with villous lymphocytes). On Bone marrow
      examination, differential diagnosis was given as splenic lymphoma with villous
      lymphocytes (SLVL) and prolymphocytic variant of Hairy cell leukemia. On flow
      cytometric analysis, these cells were positive for CD11c, CD19, CD20, and CD22.
      Based on the clinical, peripheral smear, bone marrow and flow cytometry findings,
      a diagnosis of hairy cell leukaemia variant was confirmed. The differential
      diagnosis should always include SLVL, HCL-C and Japanese variant HCL because they
      have different clinical and biological features, particularly regarding their
      response to purine analogue-based treatment or splenectomy.

PMID- 23543124
TI  - The synergistic effect of exposure to alcohol, tobacco smoke and other risk
      factors for age-related macular degeneration.

PMID- 23543125
TI  - An unresolved discussion: presence of premature ejaculation and erectile
      dysfunction in lumbar disc hernia.
AB  - PURPOSE: Premature ejaculation (PE) and erectile dysfunction (ED) are both
      frequent diseases with several questions about the aetiological factors for these
      disorders. Lumbar disc herniation (LDH), which can cause both neurological and
      physiological impairments, may be a causative reason. We prospectively tried to
      evaluate the presence of PE and ED in patients with LDH and identify the effect
      of both surgical and physical therapy treatments for LDH on PE and ED. METHODS: A
      total of 50 patients with LDH and a corresponding control group without LDH at an
      age of 18-50 years were included in the study. Both PE and ED were evaluated with
      premature ejaculation diagnostic tool (PEDT) and International Index of Erectile
      Function. Mean intravaginal ejaculatory latency time (IELT) was calculated at
      their 5 consecutive intercourse. Physical therapy or microdiscectomy was
      performed according to indication. After 6 months of follow-up, patients in
      treatment group were re-evaluated for PE and ED. RESULTS: Mean age of study and
      control group was 34.1 +/- 3.3 and 34.2 +/- 4.0 years, respectively (p = 0.979).
      In LDH group, IELT was <1 min in 12 (24 %), 1-2 (16 %) min in 8, 2-3 min in 7 (14
      %), 3-4 min in 7 (14 %) and 4 or more minutes in 16 (32 %) patients. These
      numbers were 11 (22 %), 8 (16 %), 5 (10 %), 9 (18 %) and 17 (34 %) in control
      group, respectively. Mean PEDT score of patients who had IELT < 1 min was 11.9 +/
      2.1 and 10.7 +/- 2.1 in study and control group, whereas it decreased to 1.0 +/-
      2.8 and 0.5 +/- 1.8 as IELT increased over 4 min, respectively. There were 11 (22
      %) patients with ED in LDH group, whereas there were only 2 (4 %) in control
      group (p = 0.017). Twenty patients with LDH underwent surgery while 30 had been
      taken into physical therapy. After 6 months, patients with PE significantly
      decreased in both surgery and physical therapy group (p = 0.025 and p = 0.046).
      Patients with ED also decreased after treatment, but the numbers were so limited
      for statistical evaluation. CONCLUSION: Although ED was more frequent in patients
      with LDH, PE was similar in both study and control groups, but the treatment of
      LDH had positive effects on PE and ED.

PMID- 23543126
TI  - Loss of heparin-binding protein prevents necrotizing glomerulonephritis: first
      clues hint at plasminogen activator inhibitor-1.
AB  - The orchestration of acute inflammatory kidney injury is subject to widespread
      influences and involves cytokines as well as chemokines released by resident as
      well as infiltrating cells. Although intense research efforts have been made in
      the field, it still unravels yet novel key molecules involved in the pathogenesis
      of this kidney disease. A heparin-binding growth factor denoted midkine is
      expressed by various cell types following stress of tissue damage. Specific
      functions relate to orchestration of reparative and inflammatory processes by
      promoting migration of leucocytes and release of chemokines with ensuing
      angiogenesis. Midkine appears as a double-edged sword with beneficial or harmful
      effects in injured tissues. Here, we discuss a recent publication that provides
      evidence for the beneficial role of midkine in progressive glomerulonephritis,
      most likely due to blockade of plasminogen activator inhibitor-1 release. 

PMID- 23543127
TI  - An unusual variant of urethral duplication: an addition to the Effman
      classification.
AB  - A rare association of horseshoe kidney with pyelic fusion with crossed single
      ureter along with a rare unusual variant of complete urethral duplication is
      described. We review the available literature on this rare association and
      present its management.

PMID- 23543123
TI  - Risk of Guillain-Barre syndrome after 2010-2011 influenza vaccination.
AB  - Influenza vaccination has been implicated in Guillain Barre Syndrome (GBS)
      although the evidence for this link is controversial. A case-control study was
      conducted between October 2010 and May 2011 in seven Italian Regions to explore
      the relation between influenza vaccination and GBS. The study included 176 GBS
      incident cases aged >=18 years from 86 neurological centers. Controls were
      selected among patients admitted for acute conditions to the Emergency Department
      of the same hospital as cases. Each control was matched to a case by sex, age,
      Region and admission date. Two different analyses were conducted: a matched case
      control analysis and a self-controlled case series analysis (SCCS). Case-control
      analysis included 140 cases matched to 308 controls. The adjusted matched odds
      ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8
      (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal
      infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper
      respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The
      SCCS analysis included all 176 GBS cases. Influenza vaccination was associated
      with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these
      results the attributable risk in adults ranges from two to five GBS cases per
      1,000,000 vaccinations.

PMID- 23543130
TI  - Validation of a food-frequency questionnaire for the assessment of calcium intake
      in schoolchildren aged 9-10 years.
AB  - Bone mass increases steadily until age 20-30 years, when peak bone mass (PBM) is
      acquired. Nutrition plays a critical role in achievement of the optimal
      genetically programmed PBM, with reduction in the risk of osteoporosis later in
      life. Intake of nutrients can be estimated through the use of various tools;
      typically, food-frequency questionnaires (FFQs) are used in epidemiologic
      studies. The aim of this study was to validate a 21-item, semiquantitative FFQ to
      assess important nutrient intakes for bone health in Italian schoolchildren 9-10
      years of age. Relative validation was accomplished through comparison of the 7
      days weighed food record (7D records) with an FFQ developed ad hoc, completed by
      a group of 75 Italian schoolchildren (36 females, 39 males). Agreement between
      the two methods was evaluated by Spearman's correlation test and Bland-Altman
      analysis applied on the data on intake of energy, macronutrients, and
      micronutrients. Particular attention was devoted to nutrients relevant for bone
      health. Good correlations between the two methods (FFQ and 7D records) were
      observed for all nutrients. In particular, mean dietary calcium intakes were
      725.6 mg/day (95 % CI 683.2-768.1) from 7D records and 892.4 mg/day (95 % CI
      844.6-940.2) from the FFQ. These results indicate that our FFQ for schoolchildren
      aged 9-10 years is highly acceptable as it is an accurate method that can be used
      in large-scale or epidemiological studies for the evaluation of nutrient intakes
      important for the prevention of osteoporosis in a similar population.

PMID- 23543128
TI  - MR and GR functional SNPs may modulate tobacco smoking susceptibility.
AB  - A number of studies have demonstrated that stress is involved in all aspects of
      smoking behavior, including initiation, maintenance and relapse. The
      mineralocorticoid (MR) and glucocorticoid (GR) receptors are expressed in several
      brain areas and play a key role in negative feedback of the hypothalamic
      pituitary-adrenal (HPA) axis. As nicotine increases the activation of the HPA
      axis, we wondered if functional SNPs (single nucleotide polymorphisms) in MR and
      GR coding genes (NR3C2 rs5522 and NR3C1 rs6198, respectively) may be involved in
      smoking susceptibility. The sample included 627 volunteers, of which 514 were
      never-smokers and 113 lifetime smokers. We report an interaction effect between
      rs5522 and rs6198 SNPs. The odds ratio (OR) for the presence of the NR3C2 rs5522
      Val allele in NR3C1 rs6198 G carriers was 0.18 (P = 0.007), while in rs6198 G
      noncarriers the OR was 1.83 (P = 0.027). We also found main effects of the NR3C1
      rs6198 G allele on number of cigarettes smoked per day (P = 0.027) and in total
      score of the Fagerstrom Test for Nicotine Dependence (P = 0.007). These findings
      are consistent with a possible link between NR3C2 and NR3C1 polymorphisms and
      smoking behavior and provide a first partial replication for a nominally
      significant GWAS finding between NR3C2 and tobacco smoking. 

PMID- 23543129
TI  - One-year outcome after CRT implantation in NYHA class IV in comparison to NYHA
      class III patients.
AB  - BACKGROUND: The aim of the analysis was to compare the outcome of heart failure
      patients in New York Heart Association (NYHA) class IV to that of NYHA class III
      patients 1 year after implantation of a CRT device. METHODS: The analysis was
      based on the 405 CRT patients enrolled in the MASCOT trial. At enrollment, 350
      patients (86%) were in NYHA class III and 55 (14 %) were in NYHA class IV.
      RESULTS: At 1-year follow-up, the improvement of the ejection fraction was not
      statistically significantly different between NYHA class III (+7.6 +/- 11.7%) and
      NYHA class IV patients (+9.2 +/- 14.2 %; p = 0.78). NYHA class IV patients had a
      better mean NYHA class reduction with -1.93 +/- 0.83 than NYHA class III patients
      with -0.93 +/- 0.70 (p < 0.0001). There was a greater mean quality of life
      improvement in NYHA class IV (-27.2 +/- 20.9) compared to NYHA class III (-17.7
      +/- 23.9; p = 0.02). All-cause mortality as well as cardiac mortality remained
      higher in NYHA class IV with 25.5 and 16.4% than in NYHA class III with 7.1 and
      3.1% (p < 0.0001). CONCLUSIONS: In this study, 14% of all patients receiving a
      CRT device had NYHA class IV at implantation. The data support the concept to
      implant a CRT device in NYHA class IV patients, because at 1 year after
      implantation, they experienced better symptomatic improvement compared to NYHA
      class III patients. The higher cardiac as well as non-cardiac mortality resulted
      in a fivefold higher all-cause mortality compared to NYHA class III patients.

PMID- 23543131
TI  - Reduced cholinergic and glutamatergic synaptic input to regenerated motoneurons
      after facial nerve repair in rats: potential implications for recovery of motor
      function.
AB  - Deafferentation of motoneurons after facial nerve injury is a well-documented
      phenomenon but whether synaptic inputs to facial motoneurons are completely
      restored after reinnervation is unknown. Here, we tested the hypothesis that
      deficits in motor performance after transection/suture of the facial nerve
      (facial-facial anastomosis, FFA) in adult rats are associated with incomplete
      recovery of synaptic inputs. At 2 months after FFA, we found, in congruence with
      previous results, that the amplitude of whisking had recovered to only 31 % of
      control (sham operation). In the same FFA-treated rats, estimates of number of
      chemically defined synaptic terminals in the facial nucleus by
      immunohistochemistry and stereology showed a significant loss, compared with sham
      controls, of glutamatergic terminals (-26 %) and cholinergic perisomatic boutons
      (-31 %), but not inhibitory (GABA/glycinergic) terminals (-14 %). Synaptic
      deficits were accompanied by persistent microgliosis in the facial nucleus but
      soma area, dendritic arbor volume, and total number of motoneurons were normal.
      Correlation analyses revealed significant co-variations of whisking amplitude
      with number of glutamatergic and cholinergic synapses. Compared with 2 months,
      analyses of animals at 4 months after FFA showed no attenuation of the functional
      deficit and structural aberrations with one exception, increase of inhibitory
      terminal numbers beyond control level (+11 %) leading to further reduction of the
      excitatory/inhibitory terminal ratio. We suggest that deficits in motoneuron
      innervation in the regenerated facial nucleus-reduced glutamatergic and
      cholinergic input and reduced excitatory/inhibitory terminal ratio-could
      attenuate the motor output and, thus, negatively impact the functional
      performance after facial nerve regeneration. 

PMID- 23543133
TI  - Late-gadolinium enhancement in cardiac sarcoidosis.

PMID- 23543132
TI  - Spatial analysis of diffusion tensor tractography statistics along the inferior
      fronto-occipital fasciculus with application in progressive supranuclear palsy.
AB  - BACKGROUND: The purpose of the study was to develop a method for analysis of
      diffusion parameters along white matter (WM) tracts, using spatial normalization
      based on anatomical landmarks, and to introduce the apparent area coefficient
      (AAC). The method's applicability was tested in the inferior fronto-occipital
      fasciculus (IFO) in patients with progressive supranuclear palsy (PSP) and
      healthy controls (HCs). METHODS: A framework for analysis of diffusion parameters
      was developed. Spatial normalization of the tracts was performed using anatomical
      landmarks, to avoid deformations caused by cerebral atrophy. Initially, 38 HCs
      were used to optimize a threshold for the minimal size of regions that differ
      between groups. The fractional anisotropy, mean diffusivity, AAC, and the
      hemispheric asymmetry index (AI), were compared between 11 PSP patients and 15
      HCs. RESULTS: The method was feasible for analysis of PSP patients and HCs. The
      AI showed that the observed hemispheric asymmetry of AAC was significantly larger
      in PSP patients compared with HCs in small regions of the IFO. CONCLUSIONS: The
      method was successfully employed for analysis of diffusion parameters along the
      IFO in a patient group. This method can be potentially useful in studies of WM
      diseases, with or without cerebral atrophy.

PMID- 23543134
TI  - Earlier age of dementia onset and shorter survival times in dementia patients
      with diabetes.
AB  - Diabetes is a risk factor for dementia, but relatively little is known about the
      epidemiology of the association. A retrospective population study using Western
      Australian hospital inpatient, mental health outpatient, and death records was
      used to compare the age at index dementia record (proxy for onset age) and
      survival outcomes in dementia patients with and without preexisting diabetes (n =
      25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history
      in this study population with incident dementia in years 1990-2005. Dementia
      onset and death occurred an average 2.2 years and 2.6 years earlier,
      respectively, in diabetic compared with nondiabetic patients. Age-specific
      mortality rates were increased in patients with diabetes. In an adjusted
      proportional hazard model, the death rate was increased with long-duration
      diabetes, particularly with early age onset dementia. In dementia diagnosed
      before age 65 years, those with a >=15-year history of diabetes died almost twice
      as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval:
      1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset
      occurs on average 2 years early and survival outcomes are generally poorer. The
      effect of diabetes on onset, survival, and mortality is greatest when diabetes
      develops before middle age and after 15 years' diabetes duration. The impact of
      diabetes on dementia becomes progressively attenuated in older age groups.

PMID- 23543135
TI  - Observations on in vitro and in vivo antimicrofilarial effects of Bishop's weed
      (Trachispermum ammi).
AB  - The antimicrofilarial efficacy of Trachispermum ammi extacts in vitro and in vivo
      using Setaria cervi as a model, was investigated. T. ammi seed extracts were
      prepared using different solvents (with increasing order of polarity of the
      solvent) including petroleum ether, diethyl ether, chloroform, ethyl acetate,
      acetone, ethanol, and methanol. The extracts were tested for in vitro
      antimicrofilarial activity. The ethanolic and the methanolic extracts showed
      maximum activity in causing flaccidity in the microfilariae. The extracts were
      potent even at concentrations as low as 5 MUl/ml. When orally administered to
      experimentally infected rats, the extracts eliminated circulating microfilariae
      within 2 weeks. It is inferred that the antimicrofilarial molecule(s), are polar
      in nature. They induce flaccidity in the microfilariae, by possibly inhibiting
      monoamine oxidase. This communication supplements the ethnopharmacological
      information for the use of T. ammi as an antihelminthic, and indicates that T.
      ammi could be used as a potential source of antimicrofilarial drugs.

PMID- 23543136
TI  - Targeted metabolomics profiles are strongly correlated with nutritional patterns
      in women.
AB  - Nutrition plays an important role in human metabolism and health. Metabolomics is
      a promising tool for clinical, genetic and nutritional studies. A key question is
      to what extent metabolomic profiles reflect nutritional patterns in an
      epidemiological setting. We assessed the relationship between metabolomic
      profiles and nutritional intake in women from a large cross-sectional community
      study. Food frequency questionnaires (FFQs) were applied to 1,003 women from the
      TwinsUK cohort with targeted metabolomic analyses of serum samples using the
      Biocrates Absolute-IDQTM Kit p150 (163 metabolites). We analyzed seven
      nutritional parameters: coffee intake, garlic intake and nutritional scores
      derived from the FFQs summarizing fruit and vegetable intake, alcohol intake,
      meat intake, hypo-caloric dieting and a "traditional English" diet. We studied
      the correlation between metabolite levels and dietary intake patterns in the
      larger population and identified for each trait between 14 and 20 independent
      monozygotic twins pairs discordant for nutritional intake and replicated results
      in this set. Results from both analyses were then meta-analyzed. For the
      metabolites associated with nutritional patterns, we calculated heritability
      using structural equation modelling. 42 metabolite nutrient intake associations
      were statistically significant in the discovery samples (Bonferroni P < 4 * 10-5)
      and 11 metabolite nutrient intake associations remained significant after
      validation. We found the strongest associations for fruit and vegetables intake
      and a glycerophospholipid (Phosphatidylcholine diacyl C38:6, P = 1.39 * 10-9) and
      a sphingolipid (Sphingomyeline C26:1, P = 6.95 * 10-13). We also found
      significant associations for coffee (confirming a previous association with C10
      reported in an independent study), garlic intake and hypo-caloric dieting. Using
      the twin study design we find that two thirds the metabolites associated with
      nutritional patterns have a significant genetic contribution, and the remaining
      third are solely environmentally determined. Our data confirm the value of
      metabolomic studies for nutritional epidemiologic research.

PMID- 23543137
TI  - MicroRNA-200b targets CREB1 and suppresses cell growth in human malignant glioma.
AB  - MicroRNAs can coordinately repress multiple target genes and interfere with the
      biological functions of the cell, such as proliferation and apoptosis. In the
      present study, we report that miR-200b was downregulated in malignant glioma cell
      lines and specimens. Overexpression of miR-200b suppressed the proliferation and
      colony formation of glioma cells. An oncogene encoding cAMP responsive element
      binding protein 1 (CREB1), which has been shown to be an important transcription
      factor involved in the proliferation, survival, and metastasis of tumor cells,
      was here confirmed as a direct target gene of miR-200b. CREB1 was also found to
      be present at a high level in human glioma tissues. This was inversely correlated
      with miR-200b expression. Ectopic expression of CREB1 attenuated the growth
      suppressive phenotypes of glioma cells caused by miR-200b. These results indicate
      that miR-200b targets the CREB1 gene and suppresses glioma cell growth,
      suggesting that miR-200b shows tumor-suppressive activity in human malignant
      glioma.

PMID- 23543138
TI  - O-GlcNAcylation of alphaB-crystallin regulates its stress-induced translocation
      and cytoprotection.
AB  - Under normal conditions, the ubiquitously expressed alphaB-crystallin functions
      as a chaperone. alphaB-crystallin has been implicated in a variety of
      pathologies, consistent with a build-up of protein aggregates, such as
      neuromuscular disorders, myofibrillar myopathies, and cardiomyopathies. alphaB
      crystallins' cardioprotection is partially attributed to its translocation and
      binding to cytoskeletal elements in response to stress. The triggers for this
      translocation are not clearly understood. In the heart, alphaB-crystallin
      undergoes at least three significant post-translational modifications:
      phosphorylation at ser-45 and 59 and O-GlcNAcylation (O-linked attachment of the
      monosaccharide beta-N-acetyl-glucosamine) at thr-170. Whether phosphorylation
      status drives translocation remains controversial. Therefore, we evaluated the
      role of alphaB-crystallins' O-GlcNAcylation in its stress-induced translocation
      and cytoprotection in cardiomyocytes under stress. Immunoblotting and
      precipitation experiments with anti-O-GlcNAc antibody (CTD110.6) and glycoprotein
      staining (Pro-Q Emerald) both demonstrate robust stress-induced O-GlcNAcylation
      of alphaB-crystallin. A non-O-GlcNAcylatable alphaB-crystallin mutant (alphaB
      T170A) showed diminished translocation in response to heat shock and robust
      phosphorylation at both ser-45 and ser-59. Cell survival assays show a loss of
      overexpression-associated cytoprotection with the non-glycosylatable mutant to
      multiple stresses. While ectopic expression of wild-type alphaB-crystallin
      strongly stabilized ZsProSensor, a fusion protein rapidly degraded by the
      proteasome, the non-O-GlcNAcylatable version did not. Therefore, we believe the O
      GlcNAcylation of alphaB-crystallin is a dynamic and important regulator of both
      its localization and function.

PMID- 23543139
TI  - Treatment outcomes according to neuropathic bladder sphincter dysfunction type
      after treatment of oxybutynin chloride in children with myelodysplasia.
AB  - PURPOSE: We investigated the treatment outcomes according to neuropathic bladder
      sphincter dysfunction (NBSD) type after oral oxybutynin (OBT) treatment in
      children with NBSD caused by myelodysplasia. METHODS: Among 334 pediatric
      patients who were diagnosed with NBSD caused by myelodysplasia, only children
      treated with oral OBT for more than 1 year with pre- and post-treatment
      urodynamic studies and dimercaptosuccinic acid (DMSA) were retrospectively
      reviewed. We compared pre- and post-treatment urodynamic parameters including
      maximum cystometric capacity (MCC), MCC/estimated bladder capacity (EBC), and
      compliance by NBSD type in children. We also compared renal scarring on pre- and
      post-treatment DMSA by NBSD type in children. RESULTS: Our study population was
      comprised of 81 children (45 boys and 36 girls), with a mean age of 4.2 +/- 3.4
      years. The mean follow-up duration was 4.5 (range 1.0-15.1) years. After OBT
      treatment, MCC was increased significantly in all types of NBSD from 110.3 +/-
      62.2 to 202.3 +/- 103.9 ml (p < 0.05), compliance was significantly improved from
      6.4 +/- 6.1 to 11.1 +/- 9.6 ml/cmH2O (p < 0.05), but MCC/EBC was slightly
      decreased from 75.2 +/- 46.9 to 69.8 +/- 33.3 % (p = 0.40). Sub-analyzed by NBSD
      type, the pre-treatment compliance of children with acontractile detrusor with
      spastic sphincter (n = 16) was markedly decreased compared with other types of
      NBSD. Acontractile detrusor with spastic sphincter demonstrated the worst renal
      deterioration on DMSA. CONCLUSIONS: Although increases in MCC/EBC were limited,
      oral OBT treatment markedly improved MCC and compliance in all NBSD types.
      Children who had acontractile detrusor with spastic sphincter had a relatively
      high probability of renal deterioration and required specific attention.

PMID- 23543140
TI  - Administration of the selective alpha 1A-adrenoceptor antagonist silodosin
      facilitates expulsion of size 5-10 mm distal ureteral stones, as compared to
      control.
AB  - OBJECTIVE: Recently, we reported that alpha 1A-adrenoceptor (AR) is the main
      participant in phenylephrine-induced human ureteral contraction. We therefore
      decided to carry out a prospective randomized study to evaluate the effects of
      silodosin, a selective alpha 1A AR antagonist, as a medical expulsive therapy
      (MET) for distal ureteral stones. METHODS: A total of 112 male patients, who were
      referred to our department for the management of symptomatic unilateral distal
      ureteral calculi of less than 10 mm, were randomly divided into two groups: group
      A (56 patients) who were instructed to drink 2 L of water daily and group B (56
      patients) who received the same instruction and were also given silodosin (8
      mg/daily) for a maximum of 4 weeks. Expulsion rate, expulsion time and need for
      analgesics were examined. RESULTS: The expulsion rate was 55.3 % (56 patients)
      for group A and 72.7 % (55 patients) for group B (P = 0.106). The expulsion rate
      for <5 mm was 92.9 % (28 patients) for group A and 69.2 % (26 patients) for group
      B (P = 0.053). The expulsion rate for >= 5 mm was 17.9 % (28 patients) for group
      A and 75.9 % (29 patients) for group B (P = 0.001). The expulsion time was 13.40
      +/- 5.90 and 9.29 +/- 5.91 days, respectively (P = 0.012). Analgesics were
      required 1.5 +/- 3.1 and 0.3 +/- 0.9 times, respectively (P = 0.382). Stone size
      in expulsion cases was 3.64 +/- 1.25 and 5.23 +/- 2.32 mm, respectively (P =
      0.003). CONCLUSIONS: Stone size has been identified as an important predictive
      factor for stone expulsion. Therefore, it is important that administration of
      silodosin can facilitate expulsion of 1.5 mm or larger distal ureteral stones, as
      compared to control. We believe that silodosin might have potential as a MET for
      distal ureteral stones.

PMID- 23543141
TI  - Cloning, molecular characterization and expression analysis of heat shock cognate
      70 (Hsc70) cDNA from turbot (Scophthalmus maximus).
AB  - As an essential member of the HSP70 family, heat shock cognate 70 (Hsc70) is a
      constitutively expressed molecular chaperone involved in protein metabolism. In
      this paper, turbot Hsc70 was cloned and the expression profile was also analyzed.
      The full-length cDNA of the turbot Hsc70 was 2,292 bp in length, including a 113
      bp 5' UTR, a 223-bp 3' UTR and a 1,956-bp open reading frame coding a protein
      with 651 amino acid residues. Comparison of amino acid sequence revealed the
      existence of three classical HSP70 family signature motifs, a signature
      nonapeptide and one repeat of tetrapeptide in turbot Hsc70. The turbot Hsc70
      deduced amino acids sequence exhibited 75.4-96.8 % homology with Hsp70s/Hsc70s of
      24 other known sequences. In particular, the strongest homology was found with
      the cognate members of Hsc70 subfamily and the highest identity was found with
      Japanese flounder Hsc70. Semi-quantitative RT-PCR revealed that turbot Hsc70
      transcripts were stably expressed in all tested tissues under normal
      physiological condition, while the expression levels also increased (~1.5-fold to
      ~threefold) after heat shock and bacterial infection. In addition, Hsc70
      transcripts were detected throughout embryonic development and in turbot
      embryonic cell line (TEC) in the absence of any stress. Meanwhile, it was also
      heat inducible, but not cold inducible in TEC. These results suggest that Hsc70
      gene may be involved in embryogenesis and cellular protection events under normal
      and stress condition. 

PMID- 23543142
TI  - The genome of VP3, a T7-like phage used for the typing of Vibrio cholerae.
AB  - The bacteriophage VP3 is used in a phage-biotyping scheme as one of the typing
      phages of Vibrio cholerae O1 biotype El Tor strains. Here, we have sequenced and
      analyzed its genome. The genome consists of 39,481 bp with an overall G + C
      content of 42.6 %. Fifty-two open reading frames (ORFs) were predicted. Within
      the genome, 17 highly conserved phage promoters and 6 rho-independent terminators
      were predicted. When assessed with Rluc as a reporter gene, 12 of 16 cloned VP3
      promoters showed activity in the host strain V. cholerae biotype El Tor. Based on
      the temporal expression pattern detected using reverse transcription PCR (RT
      PCR), VP3 ORFs can be classed into four groups, arranged according to their order
      in the VP3 genome. Terminators T1 and T6 are presumed to work efficiently.
      Sequencing of the typing phage VP3 of V. cholerae reveals its evolutionary
      subdivisions from the members of T7-like phages of Escherichia coli. Knowledge of
      VP3 expands the known host range of T7-like phages and will promote understanding
      the different infection mechanisms used by members of this genus. 

PMID- 23543143
TI  - Association of calcium and phosphate ions with collagen in the mineralization of
      vertebrate tissues.
AB  - Among the vertebrate species, collagen is the most abundant protein and is
      associated with mineralization of their skeleton and dentition in all tissues
      except enamel. In such tissues, bones, calcifying tendon, dentin, and cementum
      are comprised principally of type I collagen, which has been proposed as a
      template for apatite mineral formation. Recent considerations of the interaction
      between type I collagen and calcium and phosphate ions as the major constituents
      of apatite have suggested that collagen polypeptide stereochemistry underlies
      binding of these ions at sites within collagen hole and overlap regions and leads
      to nucleation of crystals. The concept is fundamental to understanding both
      normal and abnormal mineralization, and it is reviewed in this article. Given
      this background, avenues for additional research studies in vertebrate
      mineralization will also be described. The latter include, for instance, how
      mineralization events subsequent to nucleation, that is, crystal growth and
      development, occur and whether they, too, are directed by collagen stereochemical
      parameters; whether mineralization can be expected in all spaces between collagen
      molecules; whether the side chains of charged amino acid residues actually point
      toward and into the hole and overlap collagen spaces to provide putative binding
      sites for calcium and phosphate ions; and what phenomena may be responsible for
      mineralization beyond hole and overlap zones and into extracellular tissue
      regions between collagen structural units. These questions will be discussed to
      provide a broader understanding of collagen contributions to potential mechanisms
      of vertebrate mineralization. 

PMID- 23543144
TI  - "Avoiding or approaching eyes"? Introversion/extraversion affects the gaze-cueing
      effect.
AB  - We investigated whether the extra-/introversion personality dimension can
      influence processing of others' eye gaze direction and emotional facial
      expression during a target detection task. On the basis of previous evidence
      showing that self-reported trait anxiety can affect gaze-cueing with emotional
      faces, we also verified whether trait anxiety can modulate the influence of intro
      /extraversion on behavioral performance. Fearful, happy, angry or neutral faces,
      with either direct or averted gaze, were presented before the target appeared in
      spatial locations congruent or incongruent with stimuli's eye gaze direction.
      Results showed a significant influence of intra-/extraversion dimension on gaze
      cueing effect for angry, happy, and neutral faces with averted gaze. Introverts
      did not show the gaze congruency effect when viewing angry expressions, but did
      so with happy and neutral faces; extraverts showed the opposite pattern.
      Importantly, the influence of intro-/extraversion on gaze-cueing was not mediated
      by trait anxiety. These findings demonstrated that personality differences can
      shape processing of interactions between relevant social signals. 

PMID- 23543145
TI  - Functional analysis of the carS gene of Fusarium fujikuroi.
AB  - The ascomycete fungus Fusarium fujikuroi is a model system in the investigation
      of the biosynthesis of some secondary metabolites, such as gibberellins,
      bikaverin, and carotenoids. Carotenoid-overproducing mutants, generically called
      carS, are easily obtained in this fungus by standard mutagenesis procedures. Here
      we report the functional characterization of gene carS, responsible for this
      mutant phenotype. The identity of the gene was demonstrated through the finding
      of mutations in six independent carS mutants and by the complementation of one of
      them. The F. fujikuroi carS gene was able to restore the control of
      carotenogenesis in a similar deregulated mutant of Fusarium oxysporum, but only
      partially at the transcription level, indicating an unexpected complexity in the
      regulation of the pathway. Due to the pleiotropic characteristics of this
      mutation, which also modifies the production of other secondary metabolites, we
      did a screening for carS-regulated genes by subtracted cDNA hybridization. The
      results show that the carS mutation affects the regulation of numerous genes in
      addition to those of carotenogenesis. The expression of the identified genes was
      usually enhanced by light, a regulatory effect also exhibited by the carS gene.
      However, in most cases, their mRNA levels in carS mutants were similar to those
      of the wild type, suggesting a regulation that affects mRNA availability rather
      than mRNA synthesis.

PMID- 23543146
TI  - An active hAT transposable element causing bud mutation of carnation by insertion
      into the flavonoid 3'-hydroxylase gene.
AB  - The molecular mechanisms underlying spontaneous bud mutations, which provide an
      important breeding tool in carnation, are poorly understood. Here we describe a
      new active hAT type transposable element, designated Tdic101, the movement of
      which caused a bud mutation in carnation that led to a change of flower color
      from purple to deep pink. The color change was attributed to Tdic101 insertion
      into the second intron of F3'H, the gene for flavonoid 3'-hydroxylase responsible
      for purple pigment production. Regions on the deep pink flowers of the mutant can
      revert to purple, a visible phenotype of, as we show, excision of the
      transposable element. Sequence analysis revealed that Tdic101 has the
      characteristics of an autonomous element encoding a transposase. A related, but
      non-autonomous element dTdic102 was found to move in the genome of the bud mutant
      as well. Its mobilization might be the result of transposase activities provided
      by other elements such as Tdic101. In carnation, therefore, the movement of
      transposable elements plays an important role in the emergence of a bud mutation.

PMID- 23543147
TI  - Olive oil improves the intestinal absorption and bioavailability of lutein in
      lutein-deficient mice.
AB  - PURPOSE: To investigate the influence of olive (OO), groundnut (GNO), soybean
      (SBO), sunflower (SFO), rice bran (RBO), corn (CO), palm (PO) oil or mixed
      micelle (control) on absorption kinetics and bioavailability of lutein in lutein
      deficient mice. Additional aim was to correlate the activity of intestinal
      triacylglycerol lipase with intestinal and plasma lutein levels. METHODS: After
      induction of lutein deficiency, mice (n = 165) were divided into eight groups
      (OO, SFO, GNO, RBO, PO, CO, SBO and control; n = 20/group) and the remaining (n =
      5) were used as baseline (0 h). Groups were further divided into four subgroups
      (n = 5/subgroup) and were intubated with lutein (200 MUM) dispersed in different
      vegetable oils. Plasma and tissue (intestine, liver and eyes), lutein,
      triglycerides, intestinal triacylglycerol lipases and fatty acid profile of
      plasma and tissues were measured at different time intervals. RESULTS: The
      percentage area under the curve value for plasma lutein in OO and GNO was higher
      by 41.8 and 5.1 %, while it was lower in other groups (18.2-53.3 %), when
      compared to control. Similarly, the percentage area under the curve for eye
      lutein in OO and GNO groups was higher by 35.2 and 4.8 %, whereas in other groups
      it was lower (5.4-69 %) than in control. Results show that olive oil facilitates
      the lutein absorption more compared to other vegetable oils, which may be due to
      the difference in fatty acid composition and higher activity of intestinal
      triacylglycerol lipase. CONCLUSIONS: Dietary olive oil rich in oleic acid
      improves the bioavailability and accumulation of lutein in lutein-deficient mice
      by modifying the intestinal triacylglycerol lipase activity.

PMID- 23543148
TI  - Acute myocardial infarct detection with dual energy CT: correlation with single
      photon emission computed tomography myocardial scintigraphy in a canine model.
AB  - BACKGROUND: Dual-energy CT (DECT) has been used to detect myocardial infarct.
      However, few comparable studies with histopathological findings as gold standard
      have been published. PURPOSE: To investigate the accuracy of DECT iodine maps for
      detecting acute myocardial infarction compared with single photon emission
      computed tomography (SPECT) in a canine model using histopathological findings as
      the reference standard. MATERIAL AND METHODS: A model of myocardial ischemia was
      created by ligating the left anterior descending (LAD) coronary artery after
      thoracotomy in six dogs, while another three dogs undergoing thoracotomy without
      LAD ligature served as a control group. Contrast-enhanced DECT scans of the heart
      were performed, followed by resting 99mTc-MIBI SPECT myocardial perfusion imaging
      in all nine dogs before and 3 h after the procedure. Triphenyltetrazolium
      chloride (TTC) staining was performed and analyzed. In the short axis of the left
      ventricle, the wall surface was divided into 17 segments, which were assessed for
      infarcted myocardium on conventional CT from average-weighted data, DECT
      myocardial iodine maps, conventional CT plus DECT, SPECT, and histopathology.
      Inter-observer and inter-modality agreement for conventional CT, DECT myocardial
      iodine maps, and SPECT were calculated. CT value of infracted and non-infracted
      areas was measured. RESULTS: With the histopathological results as the reference
      standard, the sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), and accuracy were 75.0% (30/40), 92.0% (104/113), 76.9%
      (30/39), 91.2% (104/114), 87.6% (134/153) for conventional CT, 85.0% (34/40),
      84.1% (95/113), 65.4% (34/52), 94.1% (95/101), 84.3% (129/153) for DECT
      myocardial iodine maps; 87.5% (35/40), 92.9% (105/113), 81.4% (35/43), 95.5%
      (105/110), 91.5% (140/153) for conventional CT plus DECT; 82.5% (33/40), 90.3%
      (102/113), 75.0% (33/44), and 93.6% (102/109), 88.2% (135/153) for SPECT,
      respectively. Excellent inter-observer agreement (Kappa value >0.8) and good
      inter-modality agreement (Kappa value >0.6) for each modality were found. CT
      values of infarcted myocardium (26 +/- 22 HU, 36 +/- 33 HU, 34 +/- 16 HU) were
      lower than those of non-infarcted myocardium (115 +/- 16 HU, 121 +/- 28 HU, 123
      +/- 11 HU) on images of 140 kVp, 80 kVp, and average-weighted 120 kVp images (all
      P < 0.05). CONCLUSION: With histopathology as the reference standard, DECT
      myocardial iodine maps can detect acute myocardial infarction with diagnostic
      accuracy comparable to resting SPECT myocardial perfusion imaging in a canine
      model. DECT plus conventional CT had a potential to improve the detection of
      acute myocardial infarction.

PMID- 23543149
TI  - Usefulness of a guiding sheath for fluoroscopic stent placement in patients with
      malignant gastroduodenal obstruction.
AB  - BACKGROUND: Self-expandable metallic stent placement is widely used to manage
      malignant gastroduodenal obstructions. However, there are difficulties in
      negotiating a guidewire (GW) and a stent delivery system (SDS). PURPOSE: To
      investigate feasibility, usefulness, and safety of a guiding sheath for
      fluoroscopic stent placement in patients with malignant gastroduodenal
      obstructions. MATERIAL AND METHODS: In July 2001 to August 2011, 726 patients
      with malignant gastroduodenal obstructions underwent stent placement. Guiding
      sheath was used in patients in whom a GW could not be passed through the
      obstruction and a SDS failed to reach the obstruction. Sheath usefulness was
      evaluated based on the ability of the sheath to successfully assist. The
      technical success rate and the most frequent reasons for the use of a sheath were
      evaluated. RESULTS: The guiding sheath was needed in 148 of 726 patients (20%).
      The overall technical success rate was 98% with the guiding sheath. In two of 148
      patients, stent placement failed because, the GW could not be passed through the
      obstruction, in the other, the SDS could not be passed. A minority of patients
      reported mild discomfort. Patients with pancreatic cancer and duodenal
      obstruction were significantly more likely to require the use of guiding sheaths
      (P = 0.002, P < 0.001, respectively). CONCLUSION: Using a guiding sheath for
      fluoroscopic stent placement appears to be feasible, useful and safe in patients
      with malignant gastroduodenal obstructions.

PMID- 23543150
TI  - Morusin inhibits human cervical cancer stem cell growth and migration through
      attenuation of NF-kappaB activity and apoptosis induction.
AB  - Cancer stem cells (CSCs) are believed to be responsible for tumor metastasis,
      recurrence, and high mortality of cancer patients due to their high
      tumorigenicity resistance to chemo-radiotherapy. Morusin possesses anti-cancer
      activity through attenuation of NF-kappaB activity, which is up-regulated in
      cancer stem cells. The purpose of this study is to confirm the growth and
      migration inhibition effect of morusin on human cervical CSCs, and to clarify its
      partial mechanism of activity. Human cervical CSCs were enriched using non
      adhesive culture system. Their stemness characteristics were identified with
      tumor sphere formation, self-renewal, toluidine blue staining, migration assays,
      RT-PCR analysis, and immunofluorescence staining of putative stem cell markers,
      Oct4, SOX2, and ALDH1; the epithelial-to-mesenchymal (EMT) transition markers and
      relevant transcription factors were evaluated with Western blotting. The growth
      and migration inhibition effects of morusin on human cervical CSCs were tested by
      cell proliferation, tumor sphere formation, and transwell assay; apoptotic death
      of human cervical CSCs in response to morusin was measured with DAPI staining,
      apoptotic DNA fragmentation; NF-kappaBp65, Bcl-2, Bax, and caspase-3 protein
      expressions were detected through Western blotting. Under this non-adhesive
      culture system, typical tumor spheres appeared within 5-7 days, the tumor sphere
      formation, self-renewal, and cell migration, expressions of putative stem cell
      markers, EMT markers, and relevant transcription factors of the tumor sphere
      cells were increased significantly. After morusin treatment, the proliferation,
      tumor sphere formation, and migration of human cervical CSCs were decreased
      significantly, DAPI-stained apoptotic cells increased, apoptotic DNA
      fragmentations formed evidently; the expression levels of NF-kappaBp65 and Bcl-2
      decreased significantly, Bax, and caspase-3 increased significantly in a dose
      dependent manner. Using the non-adhesive culture system, human cervical CSCs were
      enriched and expanded. Morusin has the potential to target and kill CSCs, and can
      inhibit human cervical growth and migration through NF-kappaB attenuation
      mediated apoptosis induction.

PMID- 23543152
TI  - Multiple myeloma: so much progress, but so many unsolved questions.

PMID- 23543151
TI  - Role of mitochondrial Bax, caspases, and MAPKs for ceramide-induced apoptosis in
      renal proximal tubular cells.
AB  - It remains elusive whether crosstalk exists among mitochondrial Bax, caspases,
      and mitogen-activated protein kinases (MAPKs), and whether epidermal growth
      factor (EGF), which may activate MAPKs, affects ceramide-induced apoptosis
      through the crosstalk in renal proximal tubular cells (RPTCs). Effect of ceramide
      on expression of mitochondrial Bax and phosphorylated (p)-ERK, p38MAPK and JNK,
      that of MAPKs inhibition, and of EGF in the presence or absence of MAPKs
      inhibition on ceramide-induced apoptosis were examined in HK-2 cells. Apoptosis
      and expression of mitochondrial Bax and p-MAPKs were measured by Hoechst 33258
      staining and Western blotting. C2-ceramide, but not dihydroC2-ceramide, inactive
      C2-ceramide, induced apoptosis at 24 h. C2-ceramide enhanced the mitochondrial
      Bax expression at 1 h, which was peaked at 3-6 h and decreased at 24 h, but
      remained increased, compared to control. An inhibitor of caspases, zVAD-fmk,
      ameliorated ceramide-induced apoptosis, suggesting a role of caspases for
      ceramide-induced apoptosis. C2-ceramide enhanced the expression of p-ERK and p
      p38MAPK, but not p-JNK, at 1 h, which was increased till 24 h. An inhibitor of
      ERK, PD98059, or of p38MAPK, SB202190, failed to affect C2-ceramide-induced
      apoptosis. EGF, which enhanced the expression of p-ERK and p-p38MAPK but not p
      JNK, ameliorated C2-ceramide-induced apoptosis without affecting mitochondrial
      Bax. Inhibition of ERK or p38MAPK failed to abolish the protective effect of EGF
      on C2-ceramide-induced apoptosis. Mitochondrial Bax and caspases, but not MAPKs,
      play a role for ceramide-induced apoptosis in RPTCs. EGF ameliorates ceramide
      induced apoptosis in Bax- and MAPKs-independent pathways. The mechanism of
      ceramide-induced apoptosis and anti-apoptotic effect of EGF deserves further
      investigations.

PMID- 23543153
TI  - Morphological classification of the myelodysplastic syndromes: how much more
      education of diagnosticians is necessary?

PMID- 23543154
TI  - Towards a rational graft-versus-host disease (GVHD) prophylaxis: rituximab should
      not be forgotten.

PMID- 23543155
TI  - Farnesyl and geranylgeranyl transferase inhibitors: an anti-inflammatory effect.
      Comment to "Inhibition of protein geranylgeranylation and farnesylation protects
      against graft-versus-host disease via effects on CD4 effector T cells"
      Haematologica. 2013;98(1):31-40.

PMID- 23543156
TI  - Reply to: Towards a rational graft-versus-host disease prophylaxis: rituximab
      should not be forgotten.

PMID- 23543157
TI  - Changes in protein composition of epidermal mucus in turbot Scophthalmus maximus
      (L.) under high water temperature.
AB  - To explore the skin mucous of juvenile turbot (Scophthalmus maximus) protein
      under thermo-treatment in different temperatures (20, 23, 25, and 27  degrees C),
      the corresponding proteome maps were constructed by two-dimensional gel
      electrophoresis (2-DE), from which the peptide mass map with MALDI-TOF-TOF was
      obtained, and a novel protein of polypeptide was identified by database
      retrieval. Results show that the proteome maps varied remarkably with
      temperature, indicating the increase or decrease in protein spot. Totally, 209
      protein spots were matched in five maps in temperature using ImageMaster 2D
      Platinum 6.0. In addition, six unique protein spots were selected and identified
      with MALDI-TOF-TOF. By searching database for protein identification and function
      prediction, five proteins were confirmed, of which lectin and cytokeratin are
      highly potential as protein marker for further research. The information should
      be useful for better understanding the role of mucus as a component of innate
      immune system and for identifying genotypes that suit best to the aquiculture
      environment. These proteins could be used as potential biomarkers to
      environmental stressors in mucus for providing early warning when fish suffers in
      a dangerous situation. 

PMID- 23543158
TI  - The triple gene block movement proteins of a grape virus in the genus Foveavirus
      confer limited cell-to-cell spread of a mutant Potato virus X.
AB  - Grapevine rupestris stem pitting-associated virus (GRSPaV) is a member of the
      genus Foveavirus in the family Betaflexiviridae. The genome of GRSPaV encodes
      five proteins, among which are three movement proteins designated the triple gene
      block (TGB) proteins. The TGB proteins of GRSPaV are highly similar to their
      counterparts in Potato virus X (PVX), as reflected in size, modular structure,
      conservation of critical amino acid sequence motifs, as well as similar cellular
      localization. Based on these similarities, we predicted that the TGB proteins of
      these two viruses would be interchangeable. To test this hypothesis, we replaced
      the entire or partial sequence of PVX TGB with the corresponding regions from
      GRSPaV, creating chimeric viruses that contain the PVX backbone and different
      sequences from GRSPaV TGB. These chimeric constructs were delivered into plants
      of Nicotiana benthamiana through agro-infiltration to test whether they were
      capable of cell-to-cell and systemic movement. To our surprise, viruses derived
      from pPVX.GFP(CH3) bearing GRSPaV TGB in place of PVX TGB lost the ability to
      move either cell-to-cell or systemically. Interestingly, another chimeric virus
      resulting from pPVX.GFP(HY2) containing four TGB genes (TGB1 from PVX and TGB1-3
      from GRSPaV), exhibited limited cell-to-cell, but not systemic, movement. Our
      data question the notion that analogous movement proteins encoded by even
      distantly related viruses are functionally interchangeable and can be replaced by
      each other. These data suggest that other factors, besides the TGB proteins, may
      be required for successful intercellular and/or systemic movement of progeny
      viruses. This is the first experimental demonstration that the GRSPaV TGB
      function as movement proteins in the context of a chimeric virus and that four
      TGB genes were required to support the intercellular movement of the chimeric
      virus.

PMID- 23543159
TI  - Genomic sequence analysis of a new reassortant infectious bursal disease virus
      from commercial broiler flocks in Central China.
AB  - We report the complete nucleotide sequence of a reassortant infectious bursal
      disease (IBD) virus (IBDV) HN isolate from commercial broiler flocks in central
      China. The genome consisted of 3,232 and 2,652 nucleotides in the coding regions
      of segments A and B, respectively. Alignment of both nucleotide and deduced amino
      acid sequences and phylogenetic analysis revealed that the genome segments A and
      B of HN were derived from the attenuated strain B87 and the VV strain OKYM. This
      is a new reassortant IBDV strain that has emerged in nature, involving segment A
      of a cell-culture-adapted attenuated vaccine strain B87. 

PMID- 23543160
TI  - Body mass index and physical activity at different ages and risk of multiple
      myeloma in the NIH-AARP diet and health study.
AB  - Several studies have reported an increased risk of multiple myeloma associated
      with excess body weight. We investigated the risk of multiple myeloma in relation
      to separate measures of adiposity and energy balance at different ages in the
      National Institutes of Health-AARP Diet and Health Study, a large prospective
      cohort study in the United States. Participants completed a baseline
      questionnaire (1995-1996; n = 485,049), and a subset of participants completed a
      second questionnaire (1996-1997; n = 305,618) in which we solicited more detailed
      exposure information. Hazard ratios and 95% confidence intervals were estimated
      for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation
      to several measures of obesity and leisure time physical activity. Multiple
      myeloma risk was associated with increasing body mass index (BMI) at cohort entry
      (per 5-kg/m(2) increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI):
      1.00, 1.22); similar associations were observed for BMI at age 50 years (HR =
      1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age
      18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI.
      Risk of multiple myeloma was not associated with physical activity level at any
      age. These findings support the hypothesis that excess body weight, both in early
      adulthood and later in life, is a risk factor for multiple myeloma and suggest
      that maintaining a healthy body weight throughout life may reduce multiple
      myeloma risk.

PMID- 23543161
TI  - Adult body height of twins compared with that of singletons: a register-based
      birth cohort study of Norwegian males.
AB  - In the present study, we evaluated whether childhood differences in body height
      between singletons and twins persist into adulthood. Data from the Medical Birth
      Register of Norway were linked with data from the Norwegian National Conscript
      Service. This study used data on the 457,999 males who were born alive and
      without physical anomalies in single or twin births in Norway during 1967-1984
      and who were examined at the mandatory military conscription (age 18-20 years;
      1985-2003). For sibling comparisons, the authors selected the 1,721 sibships of
      full brothers that included at least 1 male born in a single birth and at least 1
      male born in a twin birth (4,520 persons, including 2,493 twins and 2,027
      singletons). An analysis of the total study population using generalized
      estimating equations showed that the twins were 0.6 cm (95% confidence interval:
      0.4, 0.7) shorter than were the singletons after adjustment for a series of
      background factors. The fixed-effects regression analysis of the sibships that
      included both twins and singletons showed that the twins were 0.9 cm (95%
      confidence interval: 0.6, 1.2) shorter than were their singleton brothers. The
      study suggests that male twins born in Norway during 1967-1984 were slightly
      shorter in early adulthood than were singletons. 

PMID- 23543162
TI  - How are prescribing decisions made?

PMID- 23543164
TI  - Law & psychiatry: what can we say about mental health courts today?
AB  - Mental health courts (MHCs) are a popular type of problem-solving court, and
      there is ample evidence that they reduce recidivism and increase participation in
      community-based treatment. The authors summarize evidence for the effectiveness
      of MHCs and present findings from a study in which they identified and
      characterized 346 adult and 51 juvenile MHCs currently operating in the United
      States. The continued growth of MHCs will be based in large part on funding for
      services. The Affordable Care Act will have major consequences for services
      provided to this population, and its implementation may therefore affect the
      future of MHCs. The authors note that it is preferable that people with mental
      illness not become involved in the criminal justice system in the first place.
      Despite the success of MHCs, they are not a substitute for an adequate mental
      health system.

PMID- 23543165
TI  - Personal accounts: upside down: the consumer as advisor to a psychiatrist.

PMID- 23543166
TI  - Is there a doctor in the court? Focus on parental high conflict.
AB  - The author, a California Superior Court judge who is currently assigned to family
      law court, describes certain cases of marital dissolution as "parental civil
      wars" in which a high level of conflict between parents has deleterious effects
      on children. He calls on clinicians and social services systems to improve
      interventions to address high-conflict marital dissolutions and develop
      collaborations with courts to avoid lifelong negative consequences for the
      children involved in these cases.

PMID- 23543167
TI  - Parental high conflict: the context for collaboration.

PMID- 23543168
TI  - Frequent insufficient sleep and anxiety and depressive disorders among U.S.
      community dwellers in 20 states, 2010.
AB  - OBJECTIVE: This investigation examined the association of anxiety or depressive
      disorder and frequent insufficient sleep. METHODS: Data were obtained from a 2010
      telephone survey of a population-based sample of 113,936 adults in 20 states.
      Respondents were asked how often they did not get enough rest or sleep and if
      they had ever received a diagnosis of an anxiety or depressive disorder. Frequent
      insufficient sleep was defined as insufficient rest or sleep during >= 14 of the
      past 30 days. RESULTS: Frequent insufficient sleep was reported by 27.0% of the
      sample and was significantly more common (p<.05) among respondents who reported
      both anxiety and depressive disorders (48.6%), depressive disorders only (39.0%),
      or anxiety only (37.5%) than among adults who reported neither disorder (23.1%).
      CONCLUSIONS: Frequent insufficient sleep is associated with depressive and
      anxiety disorders, and the odds of the sleep disorder are increased when both
      classes of psychiatric disorders are diagnosed.

PMID- 23543169
TI  - The representation of mental illness in Bermudian print media, 1991-2011.
AB  - OBJECTIVE: Stigmatization of persons with mental illness may be perpetuated
      through media depictions. This study analyzed changes in the depiction of mental
      illness by Bermudian newspapers over 20 years. METHODS: All articles about mental
      illness in Bermuda's newspapers in 1991, 2001, and 2011 (N=277) were coded for
      composition, language, consultations and quotations, and content. RESULTS: A
      significant increase in mental health professional consultation was demonstrated.
      Articles with a negative overall tone constituted the largest percentage of all
      articles (40%) and of articles in 2001 (43%) and 2011 (42%). A significant
      difference was found in primary theme; between 1991 and 2011, articles with an
      education and information theme dropped from 40% to 18% and articles about
      violent crime increased from 12% to 18%. CONCLUSIONS: The results may necessitate
      action from the island's advocacy groups. The findings have implications for
      discussion with the national press.

PMID- 23543170
TI  - A false dilemma and an unfair characterization of veterans.

PMID- 23543171
TI  - A false dilemma and an unfair characterization of veterans: in reply.

PMID- 23543172
TI  - Self-assessed fidelity: proceed with caution.

PMID- 23543173
TI  - Self-assessed fidelity: proceed with caution: in reply.

PMID- 23543174
TI  - Closing the knowing-doing gap.

PMID- 23543175
TI  - Psychiatrists' knowledge of their patients' job functioning.

PMID- 23543176
TI  - An update on perfect depression care.

PMID- 23543185
TI  - Replication of genetic loci for sarcoidosis in US black women: data from the
      Black Women's Health Study.
AB  - In the United States, incidence and mortality from sarcoidosis, a chronic,
      granulomatous disease, are increased in black women. In data from the Black
      Women's Health Study, a follow-up of US black women, we assessed two SNPs
      (rs2076530 and rs9268480) previously identified in the BTNL2 gene (chromosome
      6p21), of which rs4424066 and rs3817963 are perfect proxies, to determine if they
      represent independent signals of disease risk. We also assessed whether local
      ancestry in four genomic regions previously identified through admixture mapping
      was associated with sarcoidosis. Finally, we assessed the relation of global
      percent African ancestry to risk. We conducted a nested case-control study of 486
      sarcoidosis cases and 943 age- and geography-matched controls. Both BTNL2 SNPs
      were associated with risk of sarcoidosis in separate models, but in a combined
      analysis the increased risk was due to the A-allele of the rs3817963 SNP; each
      copy of the A-allele was associated with a 40 % increase in risk of sarcoidosis
      (p = 0.02) and was confirmed by our haplotypic analysis. Local African ancestry
      around the rs30533 ancestry informative marker at chromosome 5q31 was associated
      with a 29 % risk reduction (p = 0.01). Therefore, we adjusted our analysis of
      global African ancestry for number of copies of African alleles in rs30533.
      Subjects in the highest quintile of percent African ancestry had a 54 % increased
      risk of sarcoidosis. The present results from a population of African-American
      women support the role of the BTNL2 gene and the 5q31 locus in the etiology of
      sarcoidosis, and also demonstrate that percent African ancestry is associated
      with disease risk.

PMID- 23543186
TI  - Downregulation of KCNQ4 by Janus kinase 2.
AB  - Janus kinase-2 (JAK2) participates in the signaling of several hormones, growth
      factors and cytokines. Further stimulators of JAK2 include osmotic cell
      shrinkage, and the kinase activates the cell volume regulatory Na(+)/H(+)
      exchanger. The kinase may thus participate in cell volume regulation. Cell
      shrinkage is known to inhibit K(+) channels. Volume-regulatory K(+) channels
      include the voltage-gated K(+) channel KCNQ4. The present study explored the
      effect of JAK2 on KCNQ4 channel activity. KCNQ4 was expressed in Xenopus oocytes
      with or without wild-type JAK2, constitutively active (V617F)JAK2 or inactive
      (K882E)JAK2; and cell membrane conductance was determined by dual-electrode
      voltage clamp. Expression of KCNQ4 was followed by the appearance of voltage
      gated K(+) conductance. Coexpression of JAK2 or of (V617F)JAK2, but not of
      (K882E)JAK2, resulted in a significant decrease in conductance. Treatment of
      KCNQ4 and JAK2 coexpressing oocytes with the JAK2 inhibitor AG490 (40 MUM) was
      followed by an increase in conductance. Treatment of KCNQ4 expressing oocytes
      with brefeldin A (5 MUM) was followed by a decrease in conductance, which was
      similar in oocytes expressing KCNQ4 together with JAK2 as in oocytes expressing
      KCNQ4 alone. Thus, JAK2 apparently does not accelerate channel protein retrieval
      from the cell membrane. In conclusion, JAK2 downregulates KCNQ4 activity and thus
      counteracts K(+) exit, an effect which may contribute to cell volume regulation.

PMID- 23543188
TI  - Determinants of stunting in school-aged children of tehran, iran.
AB  - BACKGROUND: Limited data are available indicating associates of stunting among
      Iranian children. This study was conducted to investigate determinants of
      stunting in first grade primary school children of Tehran in 2007. METHOD: In
      this case-control study, 3147 school children were selected by multistage cluster
      random sampling method from 5 districts of Tehran. Anthropometric measurements
      were done and stunting was defined as height for age less than the 5(th)
      percentile of CDC2000 cut-off points. Eighty six stunted children were identified
      and considered as case group. After matching for age, sex and residence area, 308
      non-stunted children were randomly selected as control group. Required data were
      collected by trained nutritionists using questionnaires. RESULTS: Stunting was
      prevalent among 3.7% of the study population (girls 4.4% vs. boys 2.8%, P <
      0.05). Mean age of the studied children was 82.3 month. Children with a birth
      weight of >3000 g were less likely to be stunted (OR: 0.25: 95% CI: 0.11-0.54)
      compared with those with a birth weight of <3000 g. Being born to older mothers
      (>35 years) was associated with greater odds of being stunted (3.01; 1.19-7.60)
      compared with being born to younger mothers (<35 years). Those with fathers'
      height of >160 cm were less likely to be stunted (0.04; 0.005-0.37) than those
      whose fathers' height was less than 160 cm. CONCLUSIONS: We found that birth
      weight, maternal age and fathers' height are the major contributing factors to
      stunting in this group of Iranian children. Taking into account the determinants
      of stunting might help policy makers designing appropriate interventions.

PMID- 23543187
TI  - Lingo-1 expression is increased in essential tremor cerebellum and is present in
      the basket cell pinceau.
AB  - The Lingo-1 sequence variant has been associated with essential tremor (ET) in
      several genome-wide association studies. However, the role that Lingo-1 might
      play in pathogenesis of ET is not understood. Since Lingo-1 protein is a negative
      regulator of axonal regeneration and neurite outgrowth, it could contribute to
      Purkinje cell (PC) or basket cell axonal pathology observed in postmortem studies
      of ET brains. In this study, we used Western blotting and immunohistochemistry to
      examine Lingo-1 protein in ET vs. control brains. In Western blots, Lingo-1
      protein expression level was significantly increased in cerebellar cortex (1.56
      +/- 0.46 in ET cases vs. 0.99 +/- 0.20 in controls, p = 0.002), but was similar
      in the occipital cortex (p = 1.00) of ET cases vs. controls. Lingo-1
      immunohistochemistry in cerebellum revealed that Lingo-1 was enriched in the
      distal axonal processes of basket cells, which formed a "pinceau" structure
      around the PC axon initial segment (AIS). We found that some Lingo-1-positive
      pinceau had abnormally elongated processes, targeting PC axon segments distal to
      the AIS. In ET cases, the percentage of Lingo-1-positive pinceau that were >=30
      or >=40 MUm in length was increased 2.4- to 4.1-fold, respectively, vs. pinceau
      seen in control brains (p < 0.0001). Elongated Lingo-1-positive pinceau strongly
      correlated with number of PC axonal torpedoes and a rating of basket cell axonal
      pathology. The increased cerebellar Lingo-1 expression and elongated Lingo-1
      positive pinceau processes could contribute to the abnormal PC and basket cell
      axonal pathology and cerebellar dysfunction observed in ET.

PMID- 23543189
TI  - Maternal mortality and its causes in a tertiary center.
AB  - OBJECTIVES: To study the maternal mortality and the complications leading to
      maternal death. METHODS: A retrospective study of hospital records and death
      summaries of all maternal deaths over the period from January 2000 to August 2009
      was carried out. RESULTS: There were a total of 80 maternal deaths out of 88,443
      live births giving maternal mortality rate (MMR) of 90.45 per 100,000 live
      births. Unbooked and late referral accounted for 77.5 % of maternal deaths. The
      majority of the deaths was in 30-40-year age group and around term. Hemorrhage
      was the commonest cause of death (52.5 %), followed by sepsis (13.75 %) and
      pregnancy-induced hypertension including eclampsia (10 %). CONCLUSIONS:
      Hemorrhage, sepsis, and pregnancy-induced hypertension including eclampsia were
      found to be the direct major causes of death. Anemia and cardiac disease were
      other indirect causes of deaths.

PMID- 23543190
TI  - Semiquinone derivative isolated from Bacillus sp. INM-1 protects cellular
      antioxidant enzymes from gamma-radiation-induced renal toxicity.
AB  - This study was focused to evaluate protection of indigenous antioxidant system of
      mice against gamma radiation-induced oxidative stress using a semiquinone (SQGD)
      rich fraction isolated from Bacillus sp. INM-1. Male C57bl/6 mice were
      administered SQGD (50 mg/kgb.w.i.p.) 2 h before irradiation (10 Gy) and
      modulation in antioxidant enzymes activities was estimated at different time
      intervals and compared with irradiated mice which were not pretreated by SQGD.
      Compared to untreated controls, SQGD pretreatment significantly (p < 0.05)
      accelerates superoxide dismutase, catalase, GSH, and glutathione-S-transferase
      activities. Similarly, significant (p < 0.05) increase in the expression of
      superoxide dismutase, catalase, GSH, and glutathione-S-transferase was observed
      in irradiated mice pretreated by SQGD, compared to only irradiated groups. Total
      antioxidant status equivalent to trolox was estimated in renal tissue of the mice
      after SQGD administration. Significant ABTS(+) radical formation was observed in
      H2O2-treated kidney homogenate, due to oxidative stress in the tissue. However,
      significant decrease in the levels of ABTS(+) radical was observed in kidney
      homogenate of the mice pretreated with SQGD. Therefore, it can be concluded that
      SQGD neutralizes oxidative stress by induction of antioxidant enzymes activities
      and thus improved total antioxidant status in cellular system and hence
      contributes to radioprotection.

PMID- 23543191
TI  - Aerobic metabolism and oxidative stress tolerance in the Lactobacillus plantarum
      group.
AB  - Aerobic metabolism and response to oxidative stress and starvation were studied
      in 11 Lactobacillus plantarum, L. paraplantarum and L. pentosus strains in order
      to assess the impact of aerobic metabolism on the growth and on the stress
      response. The strains were grown in aerobiosis without supplementation (AE), with
      hemin (AEH) or with hemin and menaquinone (AEHM) supplementation and in
      anaerobiosis (AN) in a complex buffered substrate. Growth rate, biomass yield,
      glucose and O2 consumption, production of lactic acid and H2O2, catalase
      activity, oxidative and starvation stress tolerance were evaluated. Aerobic
      growth increased biomass yield in late stationary phase. Further increase in
      yield was obtained with both hemin (H) and menaquinone (M) addition. With few
      exceptions, the increase in biomass correlated with the decrease of lactic acid
      which, however, decreased in anaerobic conditions as well in some strains.
      Addition of H or H + M increased growth rate for some strains but reduced the
      duration of the lag phase. H2O2 production was found only for aerobic growth with
      no supplementation due to catalase production when hemin was supplemented. To our
      knowledge this is the first study in which the advantages of aerobic growth with
      H or H + M in improving tolerance of oxidative stress and long-term survival is
      demonstrated on several strains of the L. plantarum group. The results may have
      significant technological consequences for both starter and probiotic production.

PMID- 23543192
TI  - Application of the fracture risk assessment tool (FRAX((r))) and determination of
      suitable cut-off values during primary screening in specific health check-ups in
      Japan.
AB  - Specific health check-ups, which do not include osteoporosis screening, are
      conducted more frequently than periodic osteoporosis screening in Japan. In this
      study, we investigated the usefulness of the fracture risk assessment tool
      (FRAX((r))) during specific health check-ups, evaluated the variations in its
      usefulness for 2 consecutive years, and determined FRAX((r)) cut-off values for
      osteoporosis screening. FRAX((r)) questionnaires were distributed to subjects who
      underwent specific health check-ups in 2009 and 2010 at Asahi-machi. Subjects who
      exhibited FRAX((r)) cut-off values of >=10 % were advised to be screened at a
      medical institution. Bone mineral densities (BMDs) were measured in 201 subjects
      in 2009 and 105 subjects in 2010 after specific health check-ups, and treatment
      was initiated for 79 subjects in 2009 and 24 subjects in 2010. The number of
      subjects examined and the rate of treatment initiation following specific health
      check-ups were higher than those in subjects following periodic osteoporosis
      screening in 2009. However, the number and the rate following specific health
      check-ups dropped in 2010. According to receiver operating characteristic curves
      analyses, the sensitivity and specificity of FRAX((r)) to determine osteoporosis
      treatment were highest when the cut-off values were 8 % for men and 10.5 % for
      women. In conclusion, the combination of FRAX((r)) and specific health check-ups
      was more useful than periodic osteoporosis screening to narrow down the subjects
      and to motivate them to seek follow-up. Cut-off values for specific health check
      up using FRAX((r)) should be approximately 8 % for men and 10.5 % for women. 

PMID- 23543195
TI  - Is there any role of additional retropancreatic lymph node dissection on D2
      gastrectomy for advanced gastric cancer?
AB  - BACKGROUND: Extended lymph node dissection beyond D2 in resectable gastric cancer
      has not shown any survival benefits. However, whether the retropancreatic (No.
      13) lymph node should be dissected still remains controversial. The purpose of
      this study was to evaluate the effects of additional No. 13 lymph node dissection
      on D2 gastrectomy for gastric cancer in terms of overall survival. METHODS: From
      May 2001 to December 2006, 528 patients underwent curative resection for the
      middle- or lower-third advanced gastric cancer at the National Cancer Center,
      Korea. The patients were grouped according to whether a No. 13 lymphadenectomy
      was performed (13D+/13D-). Clinicopathological characteristics and treatment
      related factors were compared between the two groups. The overall survival was
      analyzed using the Cox proportional hazard model. RESULTS: The incidence of No.
      13 lymph node metastasis was 6.7 %. There was no significant difference in
      morbidity or mortality between the 13D+ and 13D- groups. In clinical stages I/II,
      No. 13 lymph node dissection did not affect overall survival. However, it was an
      independent prognostic factor in patients with clinical stages III/IV gastric
      cancer (hazard ratio (HR), 0.55; P = 0.022). CONCLUSIONS: Additional
      retropancreatic lymph node dissection beyond a D2 gastrectomy might be favorable
      for survival in patients with clinical stage III/IV middle- or lower-third
      gastric cancer.

PMID- 23543194
TI  - Molecular mechanisms involved in the protective effect of the chloroform extract
      of Selaginella lepidophylla (Hook. et Grev.) Spring in a lithiasic rat model.
AB  - Urolithiasis is a multifaceted process, progressing from urine supersaturation to
      the formation of mature renal calculi. Calcium oxalate, the main component of
      kidney stones, has toxicological effects on renal epithelial cells. Some
      medicinal plants have shown pharmacological effects against renal lithiasis, such
      as Selaginella lepidophylla (Hook. et Grev) Spring, a plant empirically used in
      Mexico for its diuretic and antilithiasic activity. The plant was identified and
      ground, and a chloroform extract (CE) was obtained. Urolithiasis was induced in
      Wistar female rats by administration of ethylene glycol and ammonium chloride for
      21 days. Urolithiasis rats were treated with the CE (50 mg/kg) for 21 days.
      Osmolality, creatinine, sodium and potassium concentrations were measured in
      blood and urine. Glomerular filtration rate (GFR), and electrolytic and water
      balances were calculated. Urinary oxalic acid concentration was measured.
      Apoptosis, lipoperoxidation, ROS and p-amino hippuric acid were determined in
      cortical tissue. Urolithiasis rats showed a decrease of urinary flow, GFR,
      electrolytic balance, renal tubular secretion and ATP concentration and increase
      of urinary oxalic acid, lipoperoxidation, oxidative stress and apoptosis in
      cortical tissue. After treatment with the CE, urinary flow rate, GFR and renal
      tubular secretion levels were recovered; on the other hand, serum creatinine and
      urinary oxalic acid decreased on day 21. CE of Selaginella lepidophylla prevented
      the damage caused by lithiasic process by improving the active secretion in the
      proximal tubules, counteracting the ROS and lipoperoxidation effects by oxalate
      and decreased the OAT3 expression on kidney.

PMID- 23543193
TI  - Distinctive amygdala subregions involved in emotion-modulated Stroop
      interference.
AB  - Despite the well-known role of the amygdala in mediating emotional interference
      during tasks requiring cognitive resources, no definite conclusion has yet been
      reached regarding the differential roles of functionally and anatomically
      distinctive subcomponents of the amygdala in such processes. In this study, we
      examined female participants and attempted to separate the neural processes for
      the detection of emotional information from those for the regulation of cognitive
      interference from emotional distractors by adding a temporal gap between
      emotional stimuli and a subsequent cognitive Stroop task. Reaction time data
      showed a significantly increased Stroop interference effect following emotionally
      negative stimuli compared with neutral stimuli, and functional magnetic resonance
      imaging data revealed that the anterior ventral amygdala (avAMYG) showed greater
      responses to negative stimuli compared with neutral stimuli. In addition,
      individuals who scored high in neuroticism showed greater posterior dorsal
      amygdala (pdAMYG) responses to incongruent compared with congruent Stroop trials
      following negative stimuli, but not following neutral stimuli. Taken together,
      the findings of this study demonstrated functionally distinctive contributions of
      the avAMYG and pdAMYG to the emotion-modulated Stroop interference effect and
      suggested that the avAMYG encodes associative values of emotional stimuli whereas
      the pdAMYG resolves cognitive interference from emotional distractors. 

PMID- 23543196
TI  - Assessment of advanced gastric cancer management in the United States.
AB  - BACKGROUND: Increasing attention is being placed on utilization of treatment for
      advanced malignancies. Though some suggest it is futile, recent reports have
      advocated noncurative surgery for advanced gastric cancer. Our objectives were to
      (1) assess treatment trends, (2) identify predictors of surgery, and (3) evaluate
      the effect of treatment on outcomes. METHODS: Patients with stage IV gastric
      adenocarcinoma were identified from the National Cancer Data Base (1998-2007).
      Patients who underwent emergent surgery were excluded. Models were developed to
      identify factors associated with treatment receipt and to compare adjusted
      overall survival by treatment group. RESULTS: Twenty-four percent (n = 22,430) of
      patients presented with stage IV gastric adenocarcinoma; 1.5 % (n = 414)
      underwent emergent surgery. Of the remaining 21,039 patients, 62.4 % underwent
      treatment (87.0 % chemotherapy with or without radiotherapy (C +/- RT), 5.6 %
      surgery, 7.2 % combined surgery and C +/- RT). Over the decade, surgery rates
      increased by 43 %, and C +/- RT use increased by 16 % while receipt of no
      treatment decreased by 26 % (all p < 0.001). Patients who were younger, white,
      and insured, as well as those with distal tumors were more likely to undergo
      surgery. Reasons for receiving no treatment were multifactorial but were most
      strongly associated with advanced age and being uninsured. Median survival was
      longest for patients selected to undergo surgery and C +/- RT (13.5 months)
      versus C +/- RT alone (6.1 months), surgery alone (4.8 months), or no treatment
      (1.7 months, all p < 0.001). CONCLUSIONS: Utilization of nonemergent surgical
      treatment and C +/- RT for metastatic gastric adenocarcinoma has increased
      considerably over time, especially in certain patient populations; however, the
      true utility and cost of these treatments remain unknown.

PMID- 23543197
TI  - Application of the adjuvant! Online model to Korean breast cancer patients: an
      assessment of prognostic accuracy and development of an alternative prognostic
      tool.
AB  - BACKGROUND: Adjuvant! Online (AOL) is a Web-accessible risk-assessment model that
      predicts the mortality and the benefits of adjuvant therapy for breast cancer.
      METHODS: Using the Yonsei Tumor Registry database, patients with T1-3, N0-3, M0
      breast cancer who were treated at the Yonsei Cancer Center between 1986 and 1999
      were entered into AOL version 8.0 to calculate survival. RESULTS: The median age
      of the study population was 45 years (range, 23-76 years) and the median follow
      up duration was 10.8 years (range, 0.1-25.9 years) for all 699 patients. AOL
      significantly overestimated overall survival (OS) (by 11.1 %, P < 0.001), breast
      cancer-specific survival (BCSS) (by 11.6 %, P < 0.001), and event free-free
      survival (EFS) (by 9.25 %, P < 0.001) in Korean patients. Therefore, we developed
      a Korean version of AOL (KAOL), which is a new model for prognosis based on AOL's
      parameters. The observed 10-year OS (61.4 %), BCSS (62.3 %), and EFS (59.1 %) and
      the KAOL predicted OS (61.5 %), BCSS (63.5 %) and EFS (57.6 %) were not different
      (P = 0.976, P = 0.771, and P = 0.674, respectively). CONCLUSIONS: AOL was not
      found to be suitable in Korean patients with breast cancer. The newly developed
      KAOL accurately predicted 10-year outcomes in Korean breast cancer patients.

PMID- 23543198
TI  - Sustainability of recurrent expenditure on public social welfare programmes:
      expenditure analysis of the free maternal care programme of the Ghana National
      Health Insurance Scheme.
AB  - OBJECTIVE: Sustainability of public social welfare programmes has long been of
      concern in development circles. An important aspect of sustainability is the
      ability to sustain the recurrent financial costs of programmes. A free maternal
      care programme (FMCP) was launched under the Ghana National Health Insurance
      Scheme (NHIS) in 2008 with a start-up grant from the British Government. This
      article examines claims expenditure under the programme and the implications for
      the financial sustainability of the programme, and the lessons for donor and
      public financing of social welfare programmes. METHODS: Records of reimbursement
      claims for services and medicines by women benefitting from the policy in
      participating facilities in one sub-metropolis in Ghana were analysed to gain an
      understanding of the expenditure on this programme at facility level. National
      level financial inflow and outflow (expenditure) data of the NHIS, related to
      implementation of this policy for 2008 and 2009, were reviewed to put the
      facility-based data in the national perspective. FINDINGS: A total of US$936
      450.94 was spent in 2009 by the scheme on FMCP in the sub-metropolis. The NHIS
      expenditure on the programme for the entire country in 2009 was US$49.25 million,
      exceeding the British grant of US$10.00 million given for that year.
      Subsequently, the programme has been entirely financed by the National Health
      Insurance Fund. The rapidly increasing, recurrent demands on this fund from the
      maternal delivery exemption programme-without a commensurate growth on the
      amounts generated annually-is an increasing threat to the sustainability of the
      fund. CONCLUSIONS: Provision of donor start-up funding for programmes with high
      recurrent expenditures, under the expectation that government will take over and
      sustain the programme, must be accompanied by clear long-term analysis and
      planning as to how government will sustain the programme.

PMID- 23543199
TI  - Night work and breast cancer estrogen receptor status--results from the German
      GENICA study.
AB  - OBJECTIVES: The potential mechanisms that link night-shift work with breast
      cancer have been extensively discussed. Exposure to light at night (LAN) depletes
      melatonin that has oncostatic and anti-estrogenic properties and may lead to a
      modified expression of estrogen receptor (ER) alpha. Here, we explored the
      association between shift work and breast cancer in subgroups of patients with ER
      positive and -negative tumors. METHODS: GENICA (Gene-ENvironment Interaction and
      breast CAncer) is a population-based case-control study on breast cancer with
      detailed information on shift work from 857 breast cancer cases and 892 controls.
      ER status was assessed by immunohistochemical staining. Associations between
      night-shift work and ER-positive and -negative breast cancer were analyzed with
      conditional logistic regression models, adjusted for potential confounders.
      RESULTS: ER status was assessed for 827 cases and was positive in 653 and
      negative in 174 breast tumors. Overall, 49 cases and 54 controls were "ever
      employed" in shift work including night shifts for >= 1 year. In total, "ever
      shift work" and "ever night work" were not associated with an elevated risk of ER
      positive or -negative breast tumors. Night work for >= 20 years was associated
      with a significantly elevated risk of ER-negative breast cancer [odds ratio (OR)
      4.73, 95% confidence interval (95% CI) 1.22-18.36]. CONCLUSIONS: Our case-control
      study suggests that long-term night-shift work is associated with an increased
      risk of ER-negative breast cancers. Further studies on histological subtypes and
      the analysis of other potentially relevant factors are crucial for discovering
      putative mechanisms.

PMID- 23543200
TI  - Biomechanical consequences of a posterior root tear of the lateral meniscus:
      stabilizing effect of the meniscofemoral ligament.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of different types
      of lateral meniscus root tears in terms of tibiofemoral contact stress. METHODS:
      Ten porcine knees each underwent five different testing conditions with the
      menisci intact, a simulated lateral posterior root tear with and without cutting
      the meniscofemoral ligament and with an artificial tear of the posterior root of
      the medial meniscus. Biomechanical testing was performed at 30 degrees  of
      flexion with an axial load of 100 N. A pressure sensor (st Sensor Type S2042,
      Novel, Munich) was used to measure the tibiofemoral contact area and the
      tibiofemoral contact pressure. Data were analyzed to assess the differences in
      contact area and tibiofemoral peak contact pressure among the five meniscal
      conditions. RESULTS: There was no significant difference in mean contact pressure
      between the state with the menisci intact and an isolated posterior root tear of
      the lateral meniscus. In case of a root tear and a tear of the meniscofemoral
      ligament, the contact area decreased in comparison with the intact state of the
      menisci. After additional cutting of the meniscofemoral ligament, the
      tibiofemoral contact pressure was significantly higher in comparison with the
      intact state and the avulsion injury. In the medial compartment, joint
      compression forces were significantly increased in comparison with the intact
      state after cutting the posterior root of the medial meniscus (P < 0.05).
      CONCLUSIONS: The consequence of a medial meniscus root tear is well known and was
      verified by this analysis. The results of the present study show that the
      biomechanical consequences of a lateral meniscus root tear depend on the state of
      the meniscofemoral ligament. An increase in tibiofemoral contact pressure is only
      to be expected in combined injuries of the meniscus root and the meniscofemoral
      ligaments. CLINICAL RELEVANCE: Posterior lateral meniscus root tear might have a
      better prognosis in terms of the development of osteoarthritis when the
      meniscofemoral ligament is intact.

PMID- 23543201
TI  - Is it better to shine a light, or rather to curse the darkness? Cerebral near
      infrared spectroscopy and cardiac surgery.

PMID- 23543202
TI  - Long-term survival with surgery as part of a multimodality approach for N3 lung
      cancer.
AB  - OBJECTIVES: The extension of non-small-cell lung cancer (NSCLC) to
      supraclavicular (SC) and contralateral (CL) mediastinal lymph nodes is termed N3
      and usually forbids surgical resection. However, scarce surgical series have
      reported encouraging results, and we sought to analyse our experience with this
      particular subgroup of patients. METHODS: We retrospectively reviewed the charts
      of 5857 patients undergoing surgery for NSCLC during the last 30 years in two
      French centres. Eleven patients presenting with pathological-N3 were found, and
      more closely analysed concerning lymphatic spread, surgical indication and
      prognosis. RESULTS: N3 consisted of tumoural extension to the SC (n = 5), CL
      mediastinal (n = 5) or both (SC + CL, n = 1) stations. Patients underwent
      induction treatment with chemotherapy alone (n = 4), chemoradiotherapy (n = 3) or
      first-line surgery (n = 4). All patients underwent a complete surgical resection
      of the tumour associated with ipsilateral systematic mediastinal lymph node
      dissection. Additional resection of N3 lymph nodes was performed in 8 cases.
      Adjuvant treatment included chemoradiotherapy (n = 6), chemotherapy alone (n = 1)
      or radiation therapy alone (n = 1). All 5 patients with SC-N3 presented with
      ipsilateral disease; 3 of them survived 5 years. Four patients with CL-N3
      presented with left-sided tumour and nodal extension to the 4R station, and none
      of them survived. CONCLUSIONS: Some N3-patients with specific anatomical location
      may benefit from multimodality treatment including surgery. These results support
      further prospective studies for selected N3-patients.

PMID- 23543203
TI  - Propensity-matched analysis of bilateral internal mammary artery vs single
      internal mammary artery in 7702 cases of isolated coronary artery bypass
      grafting.
AB  - OBJECTIVES: To evaluate early outcomes of bilateral internal mammary artery
      (BIMA) compared with single IMA (SIMA) in patients who underwent isolated
      coronary artery bypass grafting (CABG). METHODS: Patients who received isolated
      CABG with SIMA or BIMA were retrospectively reviewed using the Japan Adult
      Cardiovascular Surgery Database from 210 institutions for 2008 and 2009. We
      performed a one-to-one matched analysis on the basis of estimated propensity
      scores for patients receiving either SIMA or BIMA and obtained two cohorts with
      3851 patients in each group balanced for baseline characteristics out of 8136
      SIMA and 4093 BIMA patients. We compared procedures actually performed, early
      outcomes including 30-day operative mortality and details of postoperative
      complications between the groups using Pearson's chi-square test, with P < 0.05
      being statistically significant. RESULTS: Preoperative profiles in both groups
      included 20% females and 50% diabetes mellitus patients with a mean age of 67
      years. Off-pump CABG was similar in both groups, being performed 75% of the time,
      with the mean number of anastomosis being 3.1 and 3.4 in the SIMA and BIMA
      groups, respectively (P < 0.0001). Thirty-day operative mortality was 1.2% in
      both groups, and the overall incidence of postoperative complications also was
      similar, although deep sternal infection was more frequent with BIMA (1.3 of SIMA
      and 2.3% of BIMA patients; P = 0.0001), while prolonged ventilation and renal
      failure were more frequent with SIMA (P < 0.05). CONCLUSIONS: The use of BIMA did
      not affect either short-term survival as postoperative mortality was low in both
      groups, or overall morbidity despite higher incidence of deep sternal infection.

PMID- 23543204
TI  - A 17-year experience with mitral valve repair with artificial chordae in infants
      and children.
AB  - OBJECTIVES: We sought to examine our long-term results of mitral valve (MV)
      repair with expanded polytetrafluoroethylene (ePTFE) sutures and to determine the
      predictors for the outcome of this procedure. METHODS: Between 1995 and 2011, MV
      repair with chordal reconstruction by artificial chordae was achieved in 78
      patients (34 males and 44 females). Median age at repair was 1.5 years (range 3.6
      months-13.4) and weight was 9.1 kg (2.5-31.4). The mean follow-up was 8.3 years.
      A Cox proportional hazards model was used to analyse the risk factors for a
      composite outcome of death, conversion to other MV repair techniques or MV
      replacement, reoperation on MV and recurrent mitral regurgitation (MR). RESULTS:
      According to Carpentier classification, 65 (83.3%) patients were Type 2 and 13
      (16.7%) were Type 3. Mitral annuloplasty was performed in all cases, except 2.
      During MV repair, 8 (10.3%) patients were ineffective with artificial chordae and
      converted to other techniques. Six (7.7%) patients underwent MV reoperation
      (three repairs and three replacements). Freedom from MV reoperation was 92.5 and
      90.4% at 5 and 10 years, respectively. There was 1 in-hospital death. At the
      latest follow-up, moderate or more MR was observed in 3 (3.8%) patients. Risks
      for the composite outcome were low body weight at operation and Carpentier
      classification Type 3. CONCLUSIONS: MV repair with artificial chordae in infants
      and children is safe and effective and associated with a low reoperation rate.
      Further investigation into the long-term durability and biological adaptation of
      ePTFE sutures after patient growth is mandatory.

PMID- 23543205
TI  - Genetic diversity, fixation and differentiation of the freshwater snail
      Biomphalaria pfeifferi (Gastropoda, Planorbidae) in arid lands.
AB  - The freshwater snail Biomphalaria pfeifferi is the main intermediate host of
      human intestinal Bilharziasis. It is widely distributed in Africa, Madagascar and
      middle-eastern countries, and its habitat includes wetlands, and arid to semi
      arid areas. Based on analysis of 18 microsatellites, we investigated reference
      allelic variation among 30 populations of B. pfeifferi from three drainage basins
      in Dhofar, Oman (the eastern limit of its distribution). This is an arid to semi
      arid region, with a 9,000-year history of very low rainfall, but is subject to
      unpredictable and destructive flash floods. In this context we showed that
      genetic fixation was very high compared to genetic differentiation which was
      moderate and, that, relative to B. pfeifferi populations from wetlands, the
      populations in Dhofar show evidence of lower levels of genetic diversity, a
      higher degree of genetic fixation, a quasi-absence of migration, and a higher
      level of genetic drift. Despite the extreme conditions in the Dhofar habitat of
      this species, it is able to survive because of its very high self-fertilization
      (approaching 100 %) and fecundity rates. 

PMID- 23543206
TI  - An extreme test of mutational meltdown shows mutational firm up instead.
AB  - Traditionally, the accumulation of new deleterious mutations in populations or
      species in low numbers is expected to lead to a reduction in fitness and
      mutational meltdown, but in this study the opposite was observed. Beginning with
      a highly inbred populations of Drosophila melanogaster, new mutations that
      accumulated in experiments of two females and two males or of one female and one
      male each generation for 52 generations did not cause a decline in progeny
      numbers over time. Only two lines went extinct among 52 tested lines. In three of
      four experiments there was a significant increase in progeny numbers over time
      (mutational firm up), which had to be due to new beneficial, compensatory,
      overdominant, or back mutations. 

PMID- 23543208
TI  - Purification and characterization of a dehalogenase from Pseudomonas stutzeri
      DEH130 isolated from the marine sponge Hymeniacidon perlevis.
AB  - 2-haloacid dehalogenases are enzymes that are capable of degrading 2-haloacid
      compounds. These enzymes are produced by bacteria, but so far they have only been
      purified and characterized from terrestrial bacteria. The present study describes
      the purification and characterization of 2-haloacid dehalogenase from the marine
      bacterium Pseudomonas stutzeri DEH130. P. Stutzeri DEH130 contained two kinds of
      2-haloacid dehalogenase (designated as Dehalogenase I and Dehalogenase II) as
      detected in the crude cell extract after ammonium sulfate fractionation. Both
      enzymes appeared to exhibit stereo-specificity with respect to substrate.
      Dehalogenase I was a 109.9-kDa enzyme that preferentially utilized D-2
      chloropropropionate and had optimum activity at pH 7.5. Dehalogenase II, which
      preferentially utilized L-2-chloropropionate, was further purified by ion
      exchange chromatography and gel filtration. Purified Dehalogenase II appeared to
      be a dimeric enzyme with a subunit of 26.0-kDa. It had maximum activity at pH
      10.0 and a temperature of 40  degrees C. Its activity was not inhibited by DTT
      and EDTA, but strongly inhibited by Cu2+, Zn2+, and Co2+. The K(m) and V(max) for
      L-2-chloropropionate were 0.3 mM and 23.8 MUmol/min/mg, respectively. Its
      substrate specificity was limited to short chain mono-substituted 2
      halocarboxylic acids, with no activity detected toward fluoropropionate and
      monoiodoacetate. This is the first report on the purification and
      characterization of 2-haloacid dehalogenase from a marine bacterium.

PMID- 23543207
TI  - Targeting oncogenic ALK and MET: a promising therapeutic strategy for
      glioblastoma.
AB  - Glioblastoma is the most common aggressive, highly glycolytic, and lethal brain
      tumor. In fact, it is among the most commonly diagnosed lethal malignancies, with
      thousands of new cases reported in the United States each year. Glioblastoma's
      lethality is derived from a number of factors including highly active pro-mitotic
      and pro-metastatic pathways. Two factors increasingly associated with the
      intracellular signaling and transcriptional machinery required for such changes
      are anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor
      (HGFR or, more commonly MET). Both receptors are members of the receptor tyrosine
      kinase (RTK) family, which has itself gained much attention for its role in
      modulating mitosis, migration, and survival in cancer cells. ALK was first
      described as a vital oncogene in lymphoma studies, but it has since been
      connected to many carcinomas, including non-small cell lung cancer and
      glioblastoma. As the receptor for HGF, MET has also been highly characterized and
      regulates numerous developmental and wound healing events which, when upregulated
      in cancer, can promote tumor progression. The wealth of information gathered over
      the last 30 years regarding these RTKs suggests three downstream cascades that
      depend upon activation of STAT3, Ras, and AKT. This review outlines the
      significance of ALK and MET as they relate to glioblastoma, explores the
      significance of STAT3, Ras, and AKT downstream of ALK/MET, and touches on the
      potential for new chemotherapeutics targeting ALK and MET to improve glioblastoma
      patient prognosis.

PMID- 23543209
TI  - Precipitation of calcite induced by Synechocystis sp. PCC6803.
AB  - Calcite with laminate structure was successfully prepared by culturing
      Synechocystis sp. PCC6803 with different concentrations of calcium chloride
      (CaCl2) in BG11 media. S. PCC6803 was examined by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), laser confocal scanning microscope
      (LCSM) and energy dispersive spectroscopy (EDS). The effects of Ca2+
      concentrations and pH values on calcification were investigated and the micro
      morphs of the CaCO3 crystals were observed by means of SEM. These results showed
      that CaCO3 crystals could be more easily formed with increasing the concentration
      of CaCl2 in S. PCC6803 culture solution. S. PCC6803 could largely bind calcium
      ions, most of which were present in extracellular polymeric substances and on the
      cell wall. Inside the cells there were a lot of circular areas rich in calcium
      ions without the crystallization of calcium. Some cells produced a thicker
      gelatinous sheath outside of the translucent organic thin layer. And the cells
      inside also produced major changes that the original chloroplasts were almost
      transformed into starch grains whose sizes were from 0.5 to 1 MUm with relatively
      uniform in sizes. At the same time the cell sizes significantly reduced to only
      about 8-9 MUm almost changing to half of its original diameters. The calcite
      crystals with a highly preferred orientation induced by S. PCC6803 were observed
      with X-ray diffraction (XRD). A critical implication was that S. PCC6803 could
      induce bio-calcification and then mediate the further growth of CaCO3 crystals in
      the biological system.

PMID- 23543210
TI  - Upward movement of Verticillium dahliae from soil to olive plants detected by
      qPCR.
AB  - Olive trees play an important role in cultural, ecological, environmental and
      social fields, constituting in large part the Mediterranean landscape. In
      Tuscany, an important economic activity is based on olive. Unfortunately, the
      Verticillium wilt affects this species and causes vascular disease. In the
      present study, a real-time quantitative PCR approach has been used to detect and
      quantify Verticillium dahliae in soil and in olive tree tissues both in
      micropropagated and in seedling olives. The minimum amounts of V. dahliae DNA
      sequences detected in soil were 11.4 fg which is equivalent to less than one
      fungal haploid genome. In micropropagated olive the pathogen was detected in the
      leaves after 43 days, showing a vertical upward movement of the fungus from the
      culture medium to stem and leaves. A similar fungal behaviour was observed in
      inoculated olive stem where after 15 days the fungal DNA was detected from
      symptomless stem tissue above 8 cm the inoculation site. The described molecular
      approach is expected to provide a more sensitive and less time-consuming
      alternative detection method for V. dahliae than plating assay procedures, which
      were traditionally proposed as an early diagnosis method for Verticillium wilt to
      farmers and tree nursery growers. 

PMID- 23543211
TI  - Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide
      study in the Netherlands.
AB  - BACKGROUND: Recent studies suggested an improved overall survival (OS) for BRCA2-
      versus BRCA1-associated epithelial ovarian cancer (EOC), whereas the impact of
      chemotherapy is not yet clear. In a nationwide cohort, we examined the results of
      primary treatment, progression-free survival (PFS), treatment-free interval
      (TFI), and OS of BRCA1 versus BRCA2 EOC patients. METHODS: Two hundred and forty
      five BRCA1- and 99 BRCA2-associated EOC patients were identified through all
      Dutch university hospitals. Analyses were carried out with the Pearson's Chi
      square test, Kaplan-Meier, and Cox regression methods. RESULTS: BRCA1 patients
      were younger at EOC diagnosis than BRCA2 patients (51 versus 55 years; P <
      0.001), without differences regarding histology, tumor grade, and International
      Federation of Gynecology and Obstetrics (FIGO) stage. Complete response rates
      after primary treatment, including chemotherapy, did not differ between BRCA1
      (86%) and BRCA2 patients (90%). BRCA1 versus BRCA2 patients had a shorter PFS
      (median 2.2 versus 3.9 years, respectively; P = 0.006), TFI (median 1.7 versus
      2.8 years; P = 0.009), and OS (median 6.0 versus 9.7 years; P = 0.04).
      Differences could not be explained by age at diagnosis, FIGO stage or type of
      treatment. CONCLUSIONS: PFS and OS were substantially longer in BRCA2- than in
      BRCA1-associated EOC patients. While response rates after primary treatment were
      similarly high in both groups, TFI, as surrogate for chemosensitivity, was
      significantly longer in BRCA2 patients.

PMID- 23543212
TI  - Association between metabolic syndrome and bone mineral density in Korea: the
      Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2008.
AB  - Little is known regarding the exact relationship between osteoporosis and
      cardiovascular disease. Moreover, previous research on the relationships between
      components of metabolic syndrome (MetS) and bone mineral density (BMD) has
      primarily focused on women and older men; there have been few studies in younger
      men. We performed a cross-sectional study to assess whether MetS is associated
      with BMD in the femoral neck or lumbar spine in Korean adults. We further
      attempted to identify the MetS component, which is the most important factor in
      BMD. We performed a multiple regression analysis to analyze data on 2,989
      subjects from the Fourth Korea National Health and Nutrition Examination Survey.
      We examined the association between MetS and individuals MetS components and BMD.
      After adjustment for age, height, weight, smoking status, alcohol consumption and
      exercise, waist circumference (WC) and diastolic blood pressure (DBP) showed
      independent negative associations with femoral neck and spine BMD in men in all
      age groups. Triglyceride concentration was also negatively associated with
      femoral neck BMD in younger men (<45 years). In premenopausal women, WC, DBP, and
      high-density lipoprotein cholesterol were negatively associated with spine BMD.
      In postmenopausal women, WC was negatively associated with femoral neck BMD.
      These results suggest that WC in men in all age groups may be the most important
      factor in bone mineral density. 

PMID- 23543213
TI  - Expertise in clinical psychology. The effects of university training and
      practical experience on expertise in clinical psychology.
AB  - How do university training and subsequent practical experience affect expertise
      in clinical psychology? To answer this question we developed methods to assess
      psychological knowledge and the competence to diagnose, construct case
      conceptualizations, and plan psychotherapeutic treatment: a knowledge test and
      short case studies in a first study, and a complex, dynamically evolving case
      study in the second study. In our cross-sectional studies, psychology students,
      trainees in a certified postgraduate psychotherapist curriculum, and behavior
      therapists with more than 10 years of experience were tested (100 in total: 20
      each of novice, intermediate, and advanced university students, postgraduate
      trainees, and therapists). Clinical knowledge and competence increased up to the
      level of trainees but unexpectedly decreased at the level of experienced
      therapists. We discuss the results against the background of expertise research
      and the training of clinical psychologists (in Germany). Important factors for
      the continuing professional development of psychotherapists are proposed.

PMID- 23543214
TI  - Dissociation of category versus item priming in face processing: an event-related
      potential study.
AB  - The underlying specificity of visual object categorization and discrimination can
      be elucidated by studying different types of repetition priming. Here we focused
      on this issue in face processing. We investigated category priming (i.e. the
      prime and target stimuli represent different exemplars of the same object
      category) and item priming (i.e. the prime and target stimuli are exactly the
      same image), using an immediate repetition paradigm. Twenty-three subjects were
      asked to respond as fast and accurately as possible to categorize whether the
      target stimulus was a face or a building image, but to ignore the prime stimulus.
      We recorded event-related potentials (ERPs) and reaction times (RTs)
      simultaneously. The RT data showed significant effects of category priming in
      both face trials and building trials, as well as a significant effect of item
      priming in face trials. With respect to the ERPs, in face trials, no priming
      effect was observed at the P100 stage, whereas a category priming effect emerged
      at the N170 stage, and an item priming effect at the P200 stage. In contrast, in
      building trials, priming effects occurred already at the P100 stage. Our results
      indicated that distinct neural mechanisms underlie separable kinds of immediate
      repetition priming in face processing.

PMID- 23543215
TI  - FcgammaRIotaIotaB controls the potency of agonistic anti-TNFR mAbs.
AB  - Isotype plays a crucial role in therapeutic monoclonal antibody (mAb) function,
      mediated in large part through differences in Fcgamma receptor (FcgammaR)
      interaction. Monoclonal Abs such as rituximab and alemtuzumab, which bind target
      cells directly, are designed for efficient recruitment of immune effector cells
      through their activatory FcgammaR engagement to mediate maximal target cell
      killing. In this setting, binding to inhibitory FcgammaRIIB is thought to inhibit
      function, making mAbs with high activatory/inhibitory (A/I) FcgammaR binding
      ratios, such as mouse IgG2a and human IgG1, the first choice for this role. In
      contrast, exciting new data show that agonistic mAbs directed against the tumour
      necrosis factor receptor superfamily member CD40 require interaction with
      FcgammaRIIB for in vivo function. Such ligation activates antigen-presenting
      cells, promotes myeloid and CTL responses and potentially stimulates effective
      anti-cancer immunity. It appears that the role of FcgammaRIIB is to mediate mAb
      hyper-crosslinking to allow CD40 downstream intracellular signalling. Previous
      work has shown that mAbs directed against other TNFR family members, Fas and
      death receptor 5 and probably death receptor 4, also require FcgammaRIIB hyper
      crosslinking to promote target cell apoptosis, suggesting a common mechanism of
      action. In mouse models, IgG1 is optimal for these agents as it binds to
      FcgammaRIIB with tenfold higher affinity than IgG2a and hence has a relatively
      low A:I FcgammaR binding ratio. In contrast, human IgG isotypes have a
      universally low affinity for FcgammaRIIB, but in the case of human IgG1,
      engineering the Fc to increase its affinity for FcgammaRIIB can potentially
      overcome this problem. Thus, modifying the A/I binding ratio of human IgG Fc can
      be used to optimise different types of therapeutic activity by enhancing
      cytotoxic or hyper-crosslinking function.

PMID- 23543216
TI  - Intraspecific variation influences natural settlement of eastern oysters.
AB  - As populations decline, their intraspecific diversity also diminishes. Population
      decline may be exacerbated if a decrease in intraspecific diversity also reduces
      important ecological functions that maintain population numbers. Oyster reefs are
      severely overharvested, declining by ~85 % worldwide. We tested how increasing
      within-species diversity of eastern oysters (Crassostrea virginica) using
      transplants would affect recruitment of oyster larvae, a key function necessary
      to maintain future populations. If harvesting reduces population numbers, within
      species diversity, and connectivity, then oysters may lose the ability to adapt
      to changing environmental conditions as well as incur lower levels of recruitment
      that may hasten their decline. Results from laboratory and field studies
      indicated that oyster larvae use chemical cues from adult oysters and not from
      associated fouling communities to select settlement sites. To test how increasing
      within-species diversity of oysters affected recruitment, we collected oysters
      from three distinct bay systems in Texas, USA, and compared natural settlement in
      treatments where all oysters were from a single bay to a mixture of all three
      bays. Significantly greater recruitment occurred in mixed treatments in 2010,
      2011, and 2012 even though oyster recruitment varied by order of magnitude during
      this time. The net biodiversity effect was positive in all 3 years, indicating
      that increased recruitment in mixed treatments can be greater than the additive
      effect of the single bay treatments. Losing intraspecific diversity may reduce
      recruitment and lead to further declines in oyster populations, illustrating the
      need for understanding how intraspecific diversity influences ecological
      functions.

PMID- 23543217
TI  - Disturbance and trajectory of change in a stream fish community over four
      decades.
AB  - Communities can change gradually or abruptly, and directionally (to an alternate
      state) or non-directionally. We briefly review the history of theoretical and
      empirical perspectives on community change, and propose a new framework for
      viewing temporal trajectories of communities in multivariate space. We used a
      stream fish dataset spanning 40 years (1969-2008) in southern Oklahoma, USA,
      emphasizing our own 1981-2008 collections which included well-documented, extreme
      drought and flood events, to assess dynamics of and environmental factors
      affecting the fish community. We evaluated the trajectory of the Brier Creek
      community in multivariate space relative to trajectories in 27 published studies,
      and for Brier Creek fish, tested hypotheses about gradual versus event-driven
      changes and persistence of shifts to alternate states. Most species were
      persistent, qualitatively, across the four decades, but varied widely in
      abundance, with some having unusually strong reproduction after extreme droughts.
      The community had an early period of relatively gradual and directional change,
      but greater displacement than predicted at random after two consecutive extreme
      droughts midway through the study (1998 and 2000). But, the community
      subsequently returned toward its former state in the last decade. This fish
      community is characterized by species that are tolerant of environmental
      extremes, and have life history traits that facilitate population recovery. The
      community appears "loosely stable" about a long-term average condition, but the
      impacts of the two consecutive droughts were substantial, and may foretell future
      dynamics of this or other communities in a changed global climate if disturbance
      events become more frequent or severe.

PMID- 23543218
TI  - A state health service and funded religious care.
AB  - This paper analyses the role chaplaincy plays in providing religious and
      spiritual care in the UK's National Health Service. The approach considers both
      the current practice of chaplains and also the wider changes in society around
      beliefs and public service provision. Amid a small but growing literature about
      spirituality, health and illness, I shall argue that the role of the chaplain is
      changing and that such change is creating pressures on the identity and
      performance of the chaplain as a religiously authorised health worker. I shall
      question whether either orthodox belief or religious belonging have any
      significant bearing on the patients' demand for chaplaincy services. Utilising an
      example of chaplaincy work I shall argue that patient need constitutes the
      strongest platform for both practice development and an articulated understanding
      of what chaplains bring to health care. Drawing on a case study the definition
      and interpretation of spiritual need will be discussed in relation to chaplaincy
      practice. In conclusion, I shall set out the case for effective research to
      establish with greater precision the detail of the chaplain's practice within a
      state-funded health system. 

PMID- 23543219
TI  - Insulin-like growth factor-binding protein-7 (IGFBP7) transcript: A-to-I editing
      events in normal and cancerous human keratinocytes.
AB  - Non-melanoma skin cancers (NMSC) are the most common malignancies in caucasians
      worldwide. Insulin-like growth factor-binding protein-7 (IGFBP7) was suggested to
      function as a tumor suppressor gene in several cancers, and to play a role in the
      proliferation of keratinocytes. A-to-I RNA editing is a post-transcriptional
      mechanism frequently used to expand and diversify transcriptome and proteome
      repertoire in eukaryotic cells. A-to-I RNA editing can alter codons, substitute
      amino acids and affect protein sequence, structure, and function. Two editing
      sites were identified within the IGFBP7 transcript. To evaluate the expression
      and editing of IGFBP7 mRNA in NMSC compared to normal epidermis. We examined the
      expression and mRNA editing level of IGFBP7 in 22 basal cell carcinoma (BCC), 15
      squamous cell carcinoma (SCC), and 18 normal epidermis samples that were
      surgically removed from patients by the Mohs Micrographic Surgery procedure. We
      studied the effect of IGFBP7 editing on an immortalized HaCaT keratinocyte cell
      model. IGFBP7 mRNA is over expressed in BCC and SCC compared to normal epidermis.
      Moreover, the IGFBP7 transcript is highly edited in normal epidermis, but its
      editing is significantly reduced in BCC and SCC. The edited form of IGFBP7 can
      inhibit proliferation and induce senescence in cultured keratinocytes. This study
      describes for the first time A-to-I editing in the coding sequence of a tumor
      suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine
      tuning mechanism to maintain the equilibrium between proliferation and senescence
      in normal skin. 

PMID- 23543221
TI  - Wilayah (authority and governance) and its implications for Islamic bioethics: a
      Sunni Maturidi perspective.
AB  - Juridical councils that render rulings on bioethical issues for Muslims living in
      non-Muslim lands may have limited familiarity with the foundational concept of
      wilayah (authority and governance) and its implications for their authority and
      functioning. This paper delineates a Sunni Maturidi perspective on the concept of
      wilayah, describes how levels of wilayah correlate to levels of responsibility
      and enforceability, and describes the implications of wilayah when applied to
      Islamic bioethical decision making. Muslim health practitioners and patients
      living in the absence of political wilayah may be tempted to apply pragmatic and
      context-focused approaches to address bioethical dilemmas without a full
      appreciation of significant implications in the afterlife. Academic wilayah
      requires believers to seek authentication of uncertain actions through scholarly
      opinions. Fulfilling this academic obligation naturally leads to additional
      mutually beneficial discussions between Islamic scholars, healthcare
      professionals, and patients. Furthermore, an understanding derived from a
      Maturidi perspective provides a framework for Islamic scholars and Muslim health
      care professionals to generate original contributions to mainstream bioethics and
      public policy discussions.

PMID- 23543220
TI  - Synthesis, biological activity and molecular modelling studies of tricyclic
      alkylimidazo-, pyrimido- and diazepinopurinediones.
AB  - Syntheses and biological activities of imidazo-, pyrimido- and diazepino[2,1
      f]purinediones containing N-alkyl substituents (with straight, branched or
      unsaturated chains) are described. Tricyclic derivatives were synthesized by the
      cyclization of 8-bromo-substituted 7-(2-bromoethyl)-, 7-(3-chloropropyl)- or 7-(4
      bromobutyl)-theophylline with primary amines under various conditions. Compound
      22 with an ethenyl substituent was synthesized by dehydrohalogenation of 9-(2
      bromoethyl)-1,3-dimethyltetrahydropyrimido[2,1-f]purinedione. The obtained
      derivatives (5-35) were initially evaluated for their affinity at rat A1 and A2A
      adenosine receptors (AR), showing moderate affinity for both adenosine receptor
      subtypes. The best ligands were diazepinopurinedione 28 (K i = 0.28 MUM) with
      fivefold A2A selectivity and the non-selective A1/A2A AR ligand
      pyrimidopurinedione 35 (K i A1 = 0.28 MUM and K i A2A = 0.30 MUM). The compounds
      were also evaluated for their affinity at human A1, A2A, A2B and A3 ARs. All of
      the obtained compounds were docked to the A2A AR X-ray structure in complex with
      the xanthine-based, potent adenosine receptor antagonist-XAC. The likely
      interactions of imidazo-, pyrimido- and diazepino[2,1-f]purinediones with the
      residues forming the A2A binding pocket were discussed. Furthermore, the new
      compounds were tested in vivo as anticonvulsants in maximal electroshock,
      subcutaneous pentylenetetrazole (ScMet) and TOX tests in mice (i.p.).
      Pyrimidopurinediones showed anticonvulsant activity mainly in the ScMet test. The
      best derivative was compound 11, showing 100 % protection at a dose of 100 mg/kg
      without symptoms of neurotoxicity. Compounds 6, 7, 8 and 14 with short
      substituents showed neurotoxicity and caused death. In rat tests (p.o.), 9 was
      characterized by a high protection index (>13.3). AR affinity did not apparently
      correlate with the antiepileptic potency of the compounds.

PMID- 23543222
TI  - Aligning faith-based and national HIV/AIDS prevention responses? Factors
      influencing the HIV/AIDS prevention policy process and response of faith-based
      NGOs in Tanzania.
AB  - Faith-based organizations (FBOs) have a long tradition of providing HIV/AIDS
      prevention and mitigation services in Africa. The overall response of FBOs,
      however, has been controversial, particularly in regard to HIV/AIDS prevention
      and FBO's rejection of condom use and promotion, which can conflict with and
      negatively influence national HIV/AIDS prevention response efforts. This article
      reports the findings from a study that explored the factors influencing the
      HIV/AIDS prevention policy process within faith-based non-governmental
      organizations (NGOs) of different faiths. These factors were examined within
      three faith-based NGOs in Dar es Salaam, Tanzania-a Catholic, Anglican and Muslim
      organization. The research used an exploratory, qualitative case-study approach,
      and employed a health policy analysis framework, examining the context, actor and
      process factors and how they interact to form content in terms of policy and its
      implementation within each organization. Three key factors were found to
      influence faith-based NGOs' HIV/AIDS prevention response in terms of both policy
      and its implementation: (1) the faith structure in which the organizations are a
      part, (2) the presence or absence of organizational policy and (3) the
      professional nature of the organizations and its actors. The interaction between
      these factors, and how actors negotiate between them, was found to shape the
      organizations' HIV/AIDS prevention response. This article reports on these
      factors and analyses the different HIV/AIDS prevention responses found within
      each organization. By understanding the factors that influence faith-based NGOs'
      HIV/AIDS prevention policy process, the overall faith-based response to HIV/AIDS,
      and how it corresponds to national response efforts, is better understood. It is
      hoped that by doing so the government will be better able to identify how to best
      work with FBOs to meet national HIV/AIDS prevention targets, improving the
      overall role of FBOs in the fight against HIV/AIDS. 

PMID- 23543223
TI  - Tumour vasculature targeting agents in hybrid/conjugate drugs.
AB  - Tumour vasculature targeting has been a very active area of cancer drug discovery
      over the last decade. Growth of solid tumours beyond a certain point requires a
      sufficient blood supply in order for them to develop and metastasise. While novel
      anti-angiogenic and vascular disrupting agents represent an important
      contribution to the armoury of anti-cancer agents they nevertheless usually
      require combination with standard cytotoxic therapy in order to demonstrate
      positive clinical outcomes. In line with this consensus, a new concept has
      arisen, namely the design of functional hybrids where at least one component of
      the design targets a tumour angiogenic/vasculature pathway. This review will
      outline examples of such hybrid/conjugate-based approaches. Emphasis will be
      placed on their preclinical evaluation with particular focus on the RGD/NGR
      conjugates, heparin-related hybrids and antibody-drug conjugates. In conclusion,
      the benefits and shortcomings of hybrids under development will be discussed in
      the context of future directions and applications.

PMID- 23543224
TI  - The epidemiology of coeliac disease in South Wales: a 28-year perspective.
AB  - OBJECTIVES: The diagnosis of coeliac disease (CD) has increased in frequency,
      particularly since the accuracy of serological antibody testing has improved.
      Previous studies from South Wales have shown an increase in the frequency of
      diagnosis from 1983 to 2004 with a decrease in specific gastro-intestinal
      symptoms, as well as an increasing age at diagnosis. AIMS/METHODS: We aimed to
      determine whether the frequency of diagnosis, the age at presentation and the
      clinical presentation of CD have changed between 2005 and 2011 compared with
      previously published data from 1983 to 2004. We reviewed all patients with CD
      presenting to the South Wales' Regional Centre between 2005 and 2011 and compared
      the age and documented mode of presentation with previous data from the same
      area. RESULTS: 163 cases of CD were diagnosed between 2005 and 2011 (23
      cases/year) with the median age at diagnosis increasing to 14 years (range 0.8-16
      years) compared with 50 cases (8/year) between 1999 and 2004 (median age at
      diagnosis 8 years), 25 cases (2.5/year) between 1990 and 1998 and 11 cases
      (1.5/year) between 1983 and 1989. 41% presented with specific gastro-intestinal
      symptoms, 23% with non-gastro-intestinal features and 36% were asymptomatic and
      diagnosed after serological screening of high-risk groups. Compared with the most
      recent previous study from the same population, the percentage of patients
      presenting with gastro-intestinal symptoms remain similar (42% vs 41%) but
      patients diagnosed after targeted screening had increased from 26% to 36%.
      CONCLUSIONS: The frequency of diagnosis of CD in this defined population has
      continued to rise, with an increase in the median age at diagnosis, and over 50%
      of patients exhibited few or no symptoms.

PMID- 23543225
TI  - Laparoscopy-assisted anorectal pull-through in anorectal malformations: a
      reappraisal.
AB  - BACKGROUND: Anorectal malformation is a complex anomaly with a broad variety of
      expressions. There are different techniques available for correction of the
      anomaly, all with their specific morbidity. Recently, much attention has been
      paid to acquired posterior urethral diverticulum after correction of anorectal
      malformation. The aim of this retrospective study was to reappraise the
      laparoscopic approach to correction of the anorectal malformation with respect to
      what can be prevented and what can be improved. METHODS: Between July 2000 and
      July 2011, a total of 19 boys born with a high or intermediate anorectal
      malformation were admitted to our center. All patients underwent a diagnostic
      workup and were included in the follow-up protocol. Follow-up continence was
      scored according to the Krickenbeck criteria. Patients were also invited for an
      ultrasound and micturition cystourethrogram (MCUG) at follow-up to determine or
      exclude the presence of a posterior urethral diverticulum. RESULTS: All patients
      underwent a successful laparoscopy-assisted anorectal pull-through. Mean age at
      the time of surgery was 2.5 months. Mean length of hospital stay was 5 days. Mean
      follow-up was 73 months. Complications were encountered in six patients. At
      follow-up 53 % of all our patients had spontaneous bowel movements and 41 %
      needed the help of laxatives or rectal washouts. In three patients a residual
      blind ending fistula was determined on MCUG but there was no true diverticulum.
      CONCLUSION: Correction of anorectal malformation is a complex procedure with
      significant morbidity. Refinements of the technique may prevent complications and
      improve outcome in both the laparoscopic and posterior sagittal anorectoplasty.
      Acquired posterior urethral diverticulum does not necessarily need to occur more
      often with the laparoscopic approach.

PMID- 23543226
TI  - Femoral nerve blocks should be performed in the modern emergency department in
      patients with fractured femurs.

PMID- 23543227
TI  - A prospective observational study of techniques to remove corneal foreign body in
      the emergency department.
AB  - INTRODUCTION: Patients  with corneal foreign bodies (CFBs) often present to the
      emergency department (ED). However, removal techniques vary among emergency
      physicians (EPs). A prospective, single-blinded, observational study was
      performed to compare slit-lamp-aided (SLA) versus non-slit-lamp-aided (NSLA) CFB
      removal by EPs. METHODS: Five EPs enrolled consecutive patients with a CFB over 3
      months. One blinded EP reviewed patients after 3 days. The study end points were:
      change in visual acuity; visual analogue pain scale (VAS) score at 12 and 24 h;
      satisfaction rating; symptoms at follow-up; and rate of complications. RESULTS:
      54 patients were enrolled: 28 had SLA removal and 26 NSLA removal; 52 were male;
      22 had undergone previous CFB removal; six were wearing eye protection at the
      time of injury. Forty-three patients were reviewed: 26 by attendance and 18 by
      telephone. There was no difference in any end points at review. However, patients
      in the SLA group had median VAS scores that were 1.5 cm lower after 24 h than
      patients in the NSLA group (p=0.43, 95% CI -2.0 to 1.0). One patient in the SLA
      group developed keratitis. CONCLUSIONS: We show that patient satisfaction
      ratings, complications and visual acuity were similar for the two methods. There
      was a trend for increased pain in the NSLA group at 12 and 24 h. Slit-lamp
      biomicroscopy and the use of magnification to remove CFBs remains the gold
      standard of care, and more intensive training should be given to EPs at the
      departmental level, particularly in EDs that receive patients with eye injuries.

PMID- 23543228
TI  - X-rays and photocarcinogenesis in hairless mice.
AB  - It is well known that excessive X-ray radiation can cause non-melanoma skin
      cancers. With the increased incidence of sun-related skin cancer there is a need
      to investigate the combination of sunlight and X-rays. Immunocompetent
      C3.Cg/TifBomTac mice (n = 298) were divided into 12 groups. Mice were irradiated
      with 12, 29 or 50 kV X-rays. The mice received a total dose of 45 Gy. They were
      irradiated with 3 SED simulated solar radiation (SSR) either before or after
      irradiation with X-rays. The groups irradiated with X-rays alone, 0, 3, 9 and 10
      mice (0, 12, 29 and 50 kV, respectively) developed squamous cell carcinoma. In
      the groups irradiated with SSR after X-rays the development of tumours was
      significantly faster in the 50 kV group than in the corresponding control group
      (175 vs. 194 days, p < 0.001). In the groups irradiated with SSR prior to the X
      ray radiation the development of tumours was significantly faster in the 29 and
      the 50 kV groups than in the corresponding control group (175 vs. 202 days, p <
      0.001 and 158 vs. 202 days, p < 0.001, respectively). In conclusion, X-ray
      radiation alone is a weak carcinogen in hairless mice. There is an added
      carcinogenic effect if X-ray radiation is given on prior sun-exposed skin or if
      the skin is sun-exposed after X-rays. We still believe that X-ray radiation is a
      safe and effective therapy for various dermatological diseases but caution should
      be observed if a patient has severely sun-damaged skin or has a high-risk sun
      behaviour.

PMID- 23543230
TI  - A general inhibition kinetics model for ethanol production using a novel carbon
      source: sodium gluconate.
AB  - In this study, sodium gluconate was applied as a novel carbon source for the fuel
      ethanol production using an engineered Escherichia coli strain KO11 in batch
      fermentations. Ethanol and acetic acid were produced as two major products as
      well as small amount of lactic acid during the fermentation. Compared to the
      conventional carbon source glucose, the bioconversion of sodium gluconate
      possessed two distinct advantages: faster utilization rate of sodium gluconate
      (1.66 g/L per h) compared to glucose (0.996 g/L per h) and no requirement for pH
      control during fermentation. A general inhibition model including both substrate
      and products inhibitory effects was proposed, which adequately simulated batch
      fermentation kinetics at various concentrations of sodium gluconate. All of the
      products showed inhibitory effects on cell growth. The order of the inhibitory
      strength of all products and substrate was for the first time clarified in this
      study. Acetic acid was the most inhibitory product mitigating the cell growth,
      followed by ethanol and lactic acid. Sodium gluconate stimulated cell growth when
      its concentration was below 16 g/L, while it inhibited the cell growth when the
      concentration was above this concentration. It completely inhibited the cell
      growth when the concentration was 325 g/L. The high value of both the coefficient
      of determination (R (2)) and the adjusted R (2) verified the good fit of the
      model. This paper provides key insights into further engineering these strains to
      improve ethanol production.

PMID- 23543229
TI  - Anti-nociceptive and anti-edematogenic effects of glibenclamide in a model of
      acute gouty attack in rats.
AB  - OBJECTIVE AND DESIGN: We investigated the effect of glibenclamide on inflammatory
      parameters in a model of acute gouty attack in rats. TREATMENT: Intra-articular
      injection of 50 MUl of monosodium urate (MSU) crystals (1.25 mg/site) was used to
      induce gout-related inflammation. The effects of glibenclamide (1-10 mg/kg, s.c.)
      or dexamethasone (8 mg/kg, s.c., positive control) were assessed on several
      inflammation parameters. METHODS: Spontaneous nociception assessment, edema
      measurement, total and differential leucocyte counts, interleukin (IL)-1beta
      release, prostaglandin E2 production and determination of blood glucose levels
      were analyzed. Peritoneal macrophages were incubated with MSU and levels of IL
      1beta were measured. Statistical significance was assessed by one- or two-way
      analysis of variance. RESULTS: Glibenclamide (3 mg/kg) or dexamethasone (8 mg/kg)
      prevented nociception and edema induced by MSU injection in rats. Glibenclamide
      did not affect leukocyte infiltration, IL-1beta release and PGE2 production, but
      only reduced IL-1beta production by MSU-stimulated macrophages at very high
      concentration (200 MUM). Dexamethasone significantly reduced leukocyte
      infiltration, IL-1beta release and PGE2 production. Glibenclamide reduced whereas
      dexamethasone increased blood glucose levels of MSU-injected rats. CONCLUSIONS:
      Glibenclamide reduced nociception and edema, but not leukocyte infiltration, IL
      1beta release and PGE2 production. However, its substantial effect on nociception
      and edema suggests that glibenclamide can be an interesting option as an adjuvant
      treatment for pain induced by acute attacks of gout.

PMID- 23543231
TI  - YAP-mediated regulation of the chondrogenic phenotype in response to matrix
      elasticity.
AB  - Matrix elasticity exerts considerable influence on the phenotype of terminally
      differentiated chondrocytes via physical cues. The Yes-associated protein (YAP)
      transcription co-activator is recognized as a key mediator that may be involved
      in the nuclear transduction of physical cues controlling cellular behavior and
      function. However, whether substrate elasticity in the regulation of the
      chondrocyte phenotype is associated with YAP remains unclear. In this work, we
      developed micropatterned substrates with varying stiffnesses to investigate the
      function of YAP and its related Hippo pathway kinases in the regulation of
      chondrocyte phenotype on soft and stiff substrates. We found that the phenotypic
      variation of chondrocytes in response to substrate stiffness is concomitant with
      the changes in YAP localization. The downregulation of YAP expression helps to
      maintain the chondrogenic phenotype while inhibiting chondrocyte proliferation.
      Furthermore, the change in the chondrocyte phenotype response to LATS1 kinase
      inactivation in the Hippo pathway varies significantly between soft and stiff
      substrates. We also found that LATS1 kinase inactivation promotes chondrocyte
      dedifferentiation only on stiff substrate. Collectively, these findings reveal
      that YAP may be involved in the changes that occur in chondrocytes cultured on
      substrates with different stiffnesses and that these changes do not entirely
      depend on the Hippo pathway kinase LATS1. Importantly, our findings indicate that
      YAP inactivation is conducive to the maintenance of the chondrogenic phenotype,
      thereby providing new insight into articular cartilage repair and regeneration
      mechanisms. 

PMID- 23543232
TI  - Common Phenotype in Patients with Both Food and Substance Dependence: Case
      Reports.
AB  - The understanding that genes play a significant role in reward dependence and
      associated behavioral and drug addictions is highlighted in the emergence of
      Reward Deficiency Syndrome (RDS). Here we show two case reports that
      unequivocally indicate the definite commonality between food and drug addiction.
      These human cases not atypically raise the question as to how to treat these two
      seemingly diverse addictions. We suggest that research directed in an attempt to
      induce natural activation of dopaminergic reward circuitry as a form of common
      therapy may indeed be parsimonious.

PMID- 23543233
TI  - How are hydrogen bonds modified by metal binding?
AB  - We have used density functional theory calculations to investigate how the
      hydrogen-bond strength is modified when a ligand is bound to a metal using over
      60 model systems involving six metals and eight ligands frequently encountered in
      metalloproteins. We study how the hydrogen-bond geometry and energy vary with the
      nature of metal, the oxidation state, the coordination number, the ligand
      involved in the hydrogen bond, other first-sphere ligands, and different hydrogen
      bond probe molecules. The results show that, in general, the hydrogen-bond
      strength is increased for neutral ligands and decreased for negatively charged
      ligands. The size of the effect is mainly determined by the net charge of the
      metal complex, and all effects are typically decreased when the model is
      solvated. In water solution, the hydrogen-bond strength can increase by up to 37
      kJ/mol for neutral ligands, and that of negatively charged ligands can increase
      (for complexes with a negative net charge) or decrease (for positively charged
      complexes). If the net charge of the complex does not change, there is normally
      little difference between different metals or different types of complexes. The
      only exception is observed for sulphur-containing ligands (Met and Cys) and if
      the ligand is redox-active (e.g. high-valence Fe-O complexes).

PMID- 23543234
TI  - (99m)Tc(N)-DBODC(5), a potential radiolabeled probe for SPECT of multidrug
      resistance: in vitro study.
AB  - [(99m)Tc(N)(DBODC)(PNP5)](+) [DBODC is bis(N-ethoxyethyl)dithiocarbamato; PNP5 is
      bis(dimethoxypropylphosphinoethyl)ethoxyethylamine], abbreviated as (99m)Tc(N)
      DBODC(5), is a lipophilic cationic mixed compound investigated as a myocardial
      imaging agent. The findings that this tracer accumulates in mitochondrial
      structures through a mechanism mediated by the negative mitochondrial membrane
      potential and that the rapid efflux of (99m)Tc(N)-DBODC(5) from nontarget tissues
      seems to be associated with the multidrug resistance (MDR) P-glycoprotein (P-gp)
      transport function open up the possibility to extend its clinical applications to
      tumor imaging and noninvasive MDR studies. The rate of uptake at 4 and 37 
      degrees C of (99m)Tc(N)-DBODC(5) was evaluated in vitro in selected human cancer
      cell lines and in the corresponding sublines before and after P-gp and/or MDR
      associated protein (MRP) modulator/inhibitor treatment using (99m)Tc-sestamibi as
      a reference. The results indicated that (1) the uptake of both (99m)Tc(N)
      DBODC(5) and (99m)Tc-sestamibi is correlated to metabolic activity of the cells
      and (2) the cellular accumulation is connected to the level of P-gp/MRP
      expression; in fact, an enhancement of uptake in resistant cells was observed
      after treatment with opportune MDR inhibitor/modulator, indicating that the
      selective blockade of P-gp/MRP prevented efflux of the tracers. This study
      provides a preliminary indication of the applicability of (99m)Tc(N)-DBODC(5) in
      tumor imaging and in detecting P-gp/MRP-mediated drug resistance in human cancer.
      In addition, the possibility to control the hydrophobicity and pharmacological
      activity of this heterocomplex through the variation of the substituents on the
      ligands backbone without affecting the P2S2 coordinating sphere makes (99m)Tc(N)
      DBODC(5) a suitable scaffold for the preparation of a molecular probe for single
      photon emission computed tomography of MDR.

PMID- 23543235
TI  - Non-canonical H-bonds in beta-lactamases: importance of C-H...pi interactions.
AB  - beta-Lactamase production is the common mechanism of resistance of beta-lactam
      antibiotics. Knowledge of inter-residue interactions in protein structures
      increases our understanding of protein structure and stability. We have
      systematically analysed the contribution of C-H...pi interactions to the
      stability of beta-lactamases. Most of the interactions are long range and most of
      the interacting residues are evolutionarily conserved. The occurrence of C-H...pi
      interactions in active sites and metal binding sites is very low in beta
      lactamases. Hence, C-H...pi interactions are important determinants of stability
      in beta-lactamases and they may not play a significant role in specificity. The
      results from this study provide valuable insights for understanding the stability
      patterns of beta-lactamases and their relation to various other environmental
      preferences.

PMID- 23543236
TI  - Lower energy to make a corneal flap with a 60 kHz femtosecond laser reduces flap
      inflammation and corneal stromal cell death but weakens flap adhesion.
AB  - PURPOSE: To compare corneal flaps created in rabbits with a 60 kHz femtosecond
      (FS) laser using different levels of raster energy and to measure early
      inflammation, corneal stromal cell death, and late postoperative adhesion
      strength. METHODS: Sixty rabbits were divided into three groups of 20 each. A
      flap 110 um thick and 9.0 mm in diameter was made in one eye of each rabbit at
      raster energies of 0.7 uJ, 1.1 uJ, and 2.4 uJ. Histopathological evaluation for
      inflammation and apoptosis using terminal deoxynucleotidyl transferase dUTP nick
      end labeling (TUNEL) staining was performed at 4 and 24 hours after flap
      creation. The adhesion strength of the flaps was measured with a tension meter at
      1 and 3 months. RESULTS: Twenty four hours after flap creation, the 2.4 uJ group
      had more inflammatory and CD11b-positive cells than the 0.7 and 1.1 uJ groups.
      The number of TUNEL-positive cells increased with raster energy at 4 and 24
      hours. The grams of force (gf) needed to detach the flaps at 3 months was
      significantly higher in 2.4 uJ group (170 gf) than in 0.7 uJ group (97.5 gf) and
      1.1 uJ group (100 gf, p = 0.03). CONCLUSIONS: Using raster energy lower than 1.1
      uJ to make a flap with a 60 kHz FS laser decreases inflammatory cell infiltration
      and corneal stromal cell death in the central cornea but may result in a weaker
      flap than using higher raster energy (2.4 uJ).

PMID- 23543237
TI  - Morphometric study of the T6 vertebra and its three ossification centers in the
      human fetus.
AB  - PURPOSE: Knowledge on the normative growth of the spine is critical in the
      prenatal detection of its abnormalities. We aimed to study the size of T6
      vertebra in human fetuses with the crown-rump length of 115-265 mm. MATERIALS AND
      METHODS: Using the methods of computed tomography (Biograph mCT), digital image
      analysis (Osirix 3.9) and statistics, the normative growth of the T6 vertebral
      body and the three ossification centers of T6 vertebra in 55 spontaneously
      aborted human fetuses (27 males, 28 females) aged 17-30 weeks were studied.
      RESULTS: Neither male-female nor right-left significant differences were found.
      The height, transverse, and sagittal diameters of the T6 vertebral body followed
      natural logarithmic functions as y = -4.972 + 2.732 * ln(age) +/- 0.253 (R (2) =
      0.72), y = -14.862 + 6.426 * ln(age) +/- 0.456 (R (2) = 0.82), and y = -10.990 +
      4.982 * ln(age) +/- 0.278 (R (2) = 0.89), respectively. Its cross-sectional area
      (CSA) rose proportionately as y = -19.909 + 1.664 * age +/- 2.033 (R (2) = 0.89),
      whereas its volumetric growth followed the four-degree polynomial function y =
      19.158 + 0.0002 * age(4) +/- 7.942 (R (2) = 0.93). The T6 body ossification
      center grew logarithmically in both transverse and sagittal diameters as y = 
      14.784 + 6.115 * ln(age) +/- 0.458 (R (2) = 0.81) and y = -12.065 + 5.019 *
      ln(age) +/- 0.315 (R (2) = 0.87), and proportionately in both CSA and volume like
      y = -15.591 + 1.200 * age +/- 1.470 (R (2) = 0.90) and y = -22.120 + 1.663 * age
      +/- 1.869 (R (2) = 0.91), respectively. The ossification center-to-vertebral body
      volume ratio was gradually decreasing with age. On the right and left, the neural
      ossification centers revealed the following models: y = -15.188 + 6.332 * ln(age)
      +/- 0.629 (R (2) = 0.72) and y = -15.991 + 6.600 * ln(age) +/- 0.629 (R (2) =
      0.74) for length, y = -6.716 + 2.814 * ln(age) +/- 0.362 (R (2) = 0.61) and y = 
      7.058 + 2.976 * ln(age) +/- 0.323 (R (2) = 0.67) for width, y = -5.665 + 0.591 *
      age +/- 1.251 (R (2) = 0.86) and y = -11.281 + 0.853 * age +/- 1.653 (R (2) =
      0.78) for CSA, and y = -9.279 + 0.849 * age +/- 2.302 (R (2) = 0.65) and y = 
      16.117 + 1.155 * age +/- 1.832 (R (2) = 0.84) for volume, respectively.
      CONCLUSIONS: Neither sex nor laterality differences are found in the morphometric
      parameters of evolving T6 vertebra and its three ossification centers. The growth
      dynamics of the T6 vertebral body follow logarithmically for its height, and both
      sagittal and transverse diameters, linearly for its CSA, and four-degree
      polynomially for its volume. The three ossification centers of T6 vertebra
      increase logarithmically in both transverse and sagittal diameters, and linearly
      in both CSA and volume. The age-specific reference intervals for evolving T6
      vertebra present the normative values of potential relevance in the diagnosis of
      congenital spinal defects.

PMID- 23543238
TI  - Unilateral duplication of the acromioclavicular joint: case report and literature
      review.
AB  - Clavicle duplication is a rare anatomical variation of the scapular belt: only
      seven cases have been reported in the literature to date, and only one took note
      of the existence of a duplication of the acromioclavicular joint. Two hypotheses
      have been proposed to interpret this variation: genetic factors, or trauma
      occurred in the growth period. Clavicle duplication should not be mistaken for a
      quite frequent coracoclavicular joint widely described. The authors report the
      case of a left acromioclavicular joint duplication in a 51-year-old male patient
      presenting with left shoulder pain. This case was the first of literature
      providing 3D CT-scan images. 

PMID- 23543240
TI  - Influence of reactive oxygen species on human sperm functions and fertilizing
      capacity including therapeutical approaches.
AB  - BACKGROUND: Reactive oxygen species (ROS) are an array of molecules including
      oxygen-centered radicals, which are endowed with one or more unpaired electrons
      and non-radical oxygen derivatives such as hydrogen peroxide, which behave, to a
      large extent, like a double-edged sword in human sperm biology. This study aimed
      to overview the current knowledge of ROS in sperm physiology and pathology, as
      well as related therapies in spermatozoal dysfunction. METHODS: We performed this
      study by searching for keywords from PUBMED, including reactive oxygen species,
      oxidative stress, sperm function, and antioxidant therapy. RESULTS AND
      CONCLUSIONS: Low levels of ROS exert critical function in normal sperm
      physiology, such as fertilizing ability (acrosome reaction, hyperactivation,
      capacitation, and chemotaxis) and sperm motility; while increased ROS generation
      and/or decreased antioxidant capacity leads to the imbalance between oxidation
      and reduction in living systems, which is called sperm oxidative stress. This
      condition was widely considered to be a significant contributory factor to sperm
      DNA damage/apoptosis, lipid peroxidation, and reduced motility, which in turn,
      increased risk of male factor infertility/subfertility and birth defects. Under
      the current status quo, numerous subsequent studies have concentrated on
      antioxidant therapy. Although utility of such a therapeutic strategy
      significantly improved sperm function and motility in a myriad of experimental
      and clinical reports, the overall effectiveness still remains controversial
      mainly due to non-standardized assay to measure the level of ROS and sperm DNA
      damage, various antioxidant supplementation strategies, and inadequate
      fertilization and pregnancy data after clinical treatment. Therefore,
      standardized assessment and evaluation of ROS and total antioxidant capacity in
      semen should be established to keep ROS in a physiological level and prevent over
      treatment of antioxidants toward reductive stress, which should be kept in mind,
      especially in assisted reproductive procedure. Moreover, the significance of
      large sample size populations, double-blind randomized, placebo-controlled
      clinical trials of antioxidant therapies is emphasized in this review to achieve
      optimal ingredients and dosage of antioxidants for patients with reactive oxygen
      induced male fertility/subfertility.

PMID- 23543239
TI  - Maternal and neonatal outcome in triplet, quadruplet and quintuplet gestations
      following ART: a 11-year study.
AB  - OBJECTIVES: To review the maternal and fetal outcome of triplet, quadruplet and
      quintuplet gestations following ART, which were managed at a hospital over 11
      years. STUDY DESIGN: Retrospective chart review of 150 triplet, 27 quadruplet,
      and 6 quintuplet pregnancies between January 2001 and December 2011. 25 women
      aged 50-56 years with triplet pregnancies, were excluded due to lack of data. No
      prophylactic interventions were used. RESULTS: 300 triplets, 108 quadruplets, and
      30 quintuplets were born. The mean maternal age was 30.2 years (SD 4.2 years).
      Mean gestational age delivery was 32.2 weeks (SD 4.2 weeks). Maternal
      complications included preterm labor 114 (86 %), prematurity 115 (87 %), anemia
      44 (33 %) gestational diabetes 35 (27 %), preeclampsia 33 (25 %), post partum
      hemorrhage 13 (10 %). Preterm labor was diagnosed in 84 (84 %) triplets, 32 (97
      %) of quadru- and quintuplet pregnancies (P > 0.05). Prematurity and preterm
      labor were major determinants. Of the 438 fetuses born there were 57 (13 %) still
      births, 77 (18 %) neonatal deaths. 32 (7 %) were early neonatal deaths, 45 (10 %)
      late neonatal deaths. The majority died due to extreme low birth weight. 75 (17
      %) neonates had low apgar score of <7 at 5 min. 22 (5 %) infants had congenital
      anomalies. Severe respiratory distress syndrome, perinatal asphyxia, very early
      preterm delivery and perinatal mortality were higher in quadru- and quintuplets
      (P < 0.05). CONCLUSION: Preterm labor and preterm prematurity were the commonest
      complications. Neonatal mortality and morbidity was significantly increased in
      quadru- and quintuplets. Prophylactic interventions were not used in an attempt
      to prevent preterm labor.

PMID- 23543241
TI  - Three decades after Gjonnaess's laparoscopic ovarian drilling for treatment of
      PCOS; what do we know? An evidence-based approach.
AB  - BACKGROUND: The introduction of laparoscopic ovarian drilling (LOD) by Gjonnaess
      in 1984 as a substitute for ovarian wedge resection created opportunities for
      extensive research given its worldwide application for ovulation induction in
      women with polycystic ovary syndrome (PCOS). PURPOSE: To critically evaluate and
      summarize the current body of literature regarding the role of LOD for the
      management of PCOS entailing its different preoperative, operative and
      postoperative aspects. In addition, long-term efficacy, cost-effectiveness,
      patient preference and health-related quality of life issues will be evaluated
      together with other available alternatives of ovulation induction treatments.
      METHODS: A PubMed search was conducted looking for the different trials, reviews
      and various guidelines relating to the role of LOD in the management of PCOS.
      RESULTS: LOD whether unilateral or bilateral is a beneficial second-line
      treatment in infertile women with clomiphene citrate (CC)-resistant PCOS. It is
      as effective as gonadotrophin treatment but without the risk of multiple
      pregnancy or ovarian hyperstimulation and does not require intensive monitoring.
      Increased responsiveness of the ovary to CC especially in patients who remain
      anovulatory following LOD is another advantage. Recent evidence suggests that
      relatively novel oral methods of ovulation induction, e.g. CC plus metformin, CC
      plus tamoxifen, rosiglitazone plus CC and aromatase inhibitors represent a
      successful alternative to LOD in CC-resistant PCOS. Meanwhile current evidence
      does not support LOD as a first-line approach in PCOS-related anovulation or
      before IVF. CONCLUSION: LOD is currently recommended as a successful and
      economical second-line treatment for ovulation induction in women with CC
      resistant PCOS.

PMID- 23543242
TI  - A Spatial Poisson Hurdle Model for Exploring Geographic Variation in Emergency
      Department Visits.
AB  - We develop a spatial Poisson hurdle model to explore geographic variation in
      emergency department (ED) visits while accounting for zero inflation. The model
      consists of two components: a Bernoulli component that models the probability of
      any ED use (i.e., at least one ED visit per year), and a truncated Poisson
      component that models the number of ED visits given use. Together, these
      components address both the abundance of zeros and the right-skewed nature of the
      nonzero counts. The model has a hierarchical structure that incorporates patient-
      and area-level covariates, as well as spatially correlated random effects for
      each areal unit. Because regions with high rates of ED use are likely to have
      high expected counts among users, we model the spatial random effects via a
      bivariate conditionally autoregressive (CAR) prior, which introduces dependence
      between the components and provides spatial smoothing and sharing of information
      across neighboring regions. Using a simulation study, we show that modeling the
      between-component correlation reduces bias in parameter estimates. We adopt a
      Bayesian estimation approach, and the model can be fit using standard Bayesian
      software. We apply the model to a study of patient and neighborhood factors
      influencing emergency department use in Durham County, North Carolina.

PMID- 23543243
TI  - Kinetics and time dependence of the differential agglutination of acetone [AC]-
      and formalin [HS]-fixed Toxoplasma tachyzoites by serum of mice with experimental
      toxoplasmosis.
AB  - Researches to specify a serologic diagnostic test capable of determining the
      stage of toxoplasmosis, whether recent or latent, have been hampered by lack of
      knowing the real time of infection. Studying the precise kinetics of the
      differential agglutination of acetone [AC]-fixed versus that of formalin [HS]
      fixed tachyzoites (differential agglutination test or AC/HS test) by sera of mice
      during the course of toxoplasmosis and assessment of its value in the
      differentiation between recent and latent infections in mice were the aims of the
      present work. Experimental toxoplasmosis was induced in mice, sera were collected
      sequentially and AC/HS test, FAST-ELISA to determine levels of IgM and IgG and
      microscopic examination of brain for Toxoplasma cysts were done. Both AC and HS
      specific patterns in the AC/HS test were noted to be dependent on the time from
      the onset of infection. Acute patterns of the AC/HS test were observed early in
      infection till before the appearance of brain cysts. Non-acute patterns were
      obtained late on 28th day post infection coinciding with the disappearance of
      IgM, persistence of IgG and presence of cysts in brains. The AC antibody was high
      in the recent phase of infection, and then it declined to be replaced by high
      sustained level of HS antibody late in infection. In conclusion, in the presence
      of both IgM and IgG, the appearance of either equivocal pattern or the non-acute
      pattern in the AC/HS test is significant in ruling out acute infection in mice.

PMID- 23543244
TI  - Perioperative thromboprophylaxis in patients with craniotomy for brain tumours: a
      systematic review.
AB  - Venous thromboembolism (VTE) events are frequent in neurooncological patients in
      perioperative period thus increasing mortality and morbidity. The role of
      prophylaxis has not yet been established with certainty, and in various
      neurosurgery and intensive care units the practice is inconsistent. A better
      definition of the risk/cost/benefit ratio of the various methods, both mechanical
      (intermittent pneumatic compression-IPC, graduated compression stockings-GCS) and
      pharmacological (unfractionated heparin-UFH or low molecular weight heparin
      LMWH), is warranted. We aim to define the optimal prophylactic treatment in the
      perioperative period in neurooncological patients. A systematic review of the
      literature was performed in Medline, Embase and Cochrane Library. Thirteen
      randomized controlled trials (RCTs) were identified, in which physical methods
      (IPC or GCS) and/or drugs (UFH or LMWHs) were evaluated in perioperative
      prophylaxis of neurological patients, mostly with brain cancer not treated with
      anticoagulants for other diseases. The analysis was conducted on a total of 1,932
      randomized patients of whom 1,558 had brain tumours. Overall data show a trend of
      reduction of VTE in patients treated with mechanical methods (IPC or GCS) that
      should be initiated preoperatively and continued until discharge or longer in
      case of persistence of risk factors. The addition of enoxaparin starting the day
      after surgery, significantly reduces clinically manifest VTE, despite an increase
      in major bleeding events. Further studies are needed to delineate the types of
      patients with an increase of VTE risk and risk/benefits ratio of physical and
      pharmacological treatments in the perioperative period.

PMID- 23543245
TI  - Tenacibaculum halocynthiae sp. nov., a member of the family Flavobacteriaceae
      isolated from sea squirt Halocynthia roretzi.
AB  - A Gram-negative, non-spore-forming, aerobic, non-flagellated, non-gliding and rod
      shaped bacterial strain, designated P-R2A1-2(T), was isolated from sea squirt
      (Halocynthia roretzi) collected from the South Sea, Korea. It grew optimally at
      25-28  degrees C, at pH 7.0-8.0 and in the presence of 2 % (w/v) NaCl. Neighbour
      joining phylogenetic tree based on 16S rRNA gene sequences revealed that the
      strain fell within the clade comprising Tenacibaculum species. Strain P-R2A1-2(T)
      exhibited the highest 16S rRNA gene sequence similarity values of 97.6, 97.2 and
      97.0 % to Tenacibaculum aestuarii SMK-4(T), T. lutimaris TF-26(T) and T.
      aiptasiae a4(T), respectively, and of 94.5-96.8 % to the type strains of the
      other Tenacibaculum species. Strain P-R2A1-2(T) contained MK-6 as the predominant
      menaquinone and C16:1 omega7c and/or iso-C15:0 2-OH, iso-C15:0 3-OH and iso-C15:0
      as the major fatty acids. The DNA G + C content of strain P-R2A1-2(T) was 30.7
      mol % and its DNA-DNA relatedness values with the type strains of T. aestuarii,
      T. lutimaris and T. aiptasiae were 17 +/- 4.2, 21 +/- 6.1 and 16 +/- 5.2 %,
      respectively. Differential phenotypic properties, together with the phylogenetic
      and genetic distinctiveness, revealed that the novel strain is separate from
      other Tenacibaculum species. On the basis of the data presented, strain P-R2A1
      2(T) is considered to represent a novel species of the genus Tenacibaculum, for
      which the name Tenacibaculum halocynthiae sp. nov. is proposed. The type strain
      is P-R2A1-2(T) (=KCTC 32262(T )= CCUG 63681(T)).

PMID- 23543246
TI  - A Clinico-Pathological Study of Lichenoid Tissue Reactions-A Tertiary Care
      experience.
AB  - INTRODUCTION: The aim of this article was to study the spectrum of clinico
      histopathological lesions with an age and sex distribution in various lichenoid
      reactions of the skin. The spectrum of clinical diseases which is related to the
      lichenoid tissue reaction is wider. There is a recent increase in the relatively
      new subgroups of the lichenoid clinical picture. MATERIAL AND METHODS: This was a
      one and a half year prospective study which was conducted in the Dermatopathology
      Section of the Department of Pathology, from January 2011 to June 2012. All the
      patients who visited the Dermatology Outpatients/ Inpatients Department and
      presented with lichenoid tissue reactions were included in the study. The
      selected patients' clinical findings were noted and their informed consents and
      an institutional ethical clearance were taken. Light microscopy was used for the
      histopathological diagnosis. The SPSS, version 14 software was used to analyze
      the data. Frequencies and percentages were used to describe the data. RESULTS:
      During the study period, 107 cases were clinically diagnosed as lichenoid
      reactions, of which 84 cases were concordant on histopathology and 6 cases were
      diagnosed, solely based on the histology. So, a total of 90 cases were diagnosed
      histologically, of which 42 were of the Lichen planus type and 48 were lichenoid
      eruptions. Females were affected more commonly than the males. CONCLUSION: In our
      study, the lichenoid reactions were more common in children and the most common
      prototype was Lichen planus. So, we conclude that histopathology is a dependable
      tool for identifying the underlying cause in lichenoid reactions.

PMID- 23543247
TI  - Diseases of pigeon in and around Kolkata, India.
AB  - The present study was undertaken to survey and study the prevalence of different
      diseases in pigeons in regions in and around Kolkata, India. About 8,000 pigeons
      from Kolkata region and 2,000 from semi-urban area surrounding Kolkata were
      selected and 5,000 fecal specimens were collected from apparently unhealthy
      pigeons. From the present study, it was evident that star gazing, diarrhea and
      pox were the major infections. Protozona parasites were also revealed which was
      caused mainly due to coccidian oocysts. In the present study it was found that
      the pigeons mainly suffered from star gazing condition and helminthic infection
      revealed majorly the presence of coccidian oocysts followed by Capillarea and
      Ascaridia spp.

PMID- 23543248
TI  - Early and parallel processing of pragmatic and semantic information in speech
      acts: neurophysiological evidence.
AB  - Although language is a tool for communication, most research in the neuroscience
      of language has focused on studying words and sentences, while little is known
      about the brain mechanisms of speech acts, or communicative functions, for which
      words and sentences are used as tools. Here the neural processing of two types of
      speech acts, Naming and Requesting, was addressed using the time-resolved event
      related potential (ERP) technique. The brain responses for Naming and Request
      diverged as early as ~120 ms after the onset of the critical words, at the same
      time as, or even before, the earliest brain manifestations of semantic word
      properties could be detected. Request-evoked potentials were generally larger in
      amplitude than those for Naming. The use of identical words in closely matched
      settings for both speech acts rules out explanation of the difference in terms of
      phonological, lexical, semantic properties, or word expectancy. The cortical
      sources underlying the ERP enhancement for Requests were found in the fronto
      central cortex, consistent with the activation of action knowledge, as well as in
      the right temporo-parietal junction (TPJ), possibly reflecting additional
      implications of speech acts for social interaction and theory of mind. These
      results provide the first evidence for surprisingly early access to pragmatic and
      social interactive knowledge, which possibly occurs in parallel with other types
      of linguistic processing, and thus supports the near-simultaneous access to
      different subtypes of psycholinguistic information.

PMID- 23543249
TI  - Pulmonary tuberculoma and miliary tuberculosis in silicosis.
AB  - Tuberculosis is a disease with protean manifestations. We present a case which
      was initially suspected as bronchogenic carcinoma with lymphangitic
      carcinomatosis, based on radiological appearance but later diagnosed as pulmonary
      tuberculoma with military tuberculosis and silicosis after thoracotomy and open
      lung biopsy. The patient was treated successfully with Antituberculosis Therapy
      (ATT). Rarity of presentation in form of pulmonary tuberculoma co-existing with
      histological features of miliary tuberculosis and silicosis, led us to report
      this case.

PMID- 23543250
TI  - Iron's role in paediatric restless legs syndrome - a review.
AB  - Paediatric restless legs syndrome (RLS) treatment is important because RLS's
      associated sleep disturbance causes significant developmental-behavioural
      morbidity and impacts family well-being. RLS is associated with brain iron
      insufficiency and dopaminergic dysfunction. Diagnosis requires fulfillment of
      diagnostic criteria, which for children are currently in evolution, and have
      limitations, especially in preschoolers. The community physician needs to
      recognize the possibility of RLS to refer to a sleep specialist for diagnostic
      confirmation and management recommendations, which include oral iron therapy,
      even though there is currently no definitive research evidence for iron efficacy
      in most children with RLS. A 3 mg to 6 mg elemental iron/kg/day dose for three
      months could be tried if the ferritin level is <50 ug/L. Sleep hygiene and
      behavioural strategies are also recommended. Iron supplementation should be safe
      in the absence of iron metabolism disorders, provided that transferrin saturation
      and ferritin levels are monitored pre-and post-treatment.

PMID- 23543252
TI  - The clinical spectrum of Trichomonas vaginalis infection and challenges to
      management.
AB  - Trichomonas vaginalis is the most common curable sexually transmitted infection
      worldwide. T vaginalis infections in women can range from asymptomatic to acute
      inflammatory vaginitis. In men, this infection is typically asymptomatic but is
      increasingly being recognised as a cause of non-gonococcal urethritis. Diagnosis
      of T vaginalis has traditionally been made by direct microscopic examination of a
      wet mount of vaginal fluid or through the use of culture. The recent commercial
      availability of nucleic acid amplification tests for the detection of T vaginalis
      has seen these replace culture as the gold standard for diagnosis.
      Nitroimidazoles (ie, metronidazole and tinidazole) are the mainstay of therapy.
      In the case of treatment failure due to drug resistance or in the case of a
      severe nitroimidazole allergy, alternative intravaginal therapies exist, although
      their effectiveness has not been evaluated systematically. Novel systemic agents
      other than nitroimidazoles for the treatment of T vaginalis are needed, and
      efforts to promote and support antimicrobial drug development in this setting are
      necessary. 

PMID- 23543253
TI  - Lacrimal gland prolapse in two cases of blepharochalasis syndrome and its
      treatment.
AB  - Blepharochalasis is a rare disorder characterized by recurrent non-painful eyelid
      edema, which leads to atrophy and stretching of the supporting connective tissue
      around the eye. As a consequence, prolapse of the lacrimal gland can occur which
      results in fullness in the temporal third of the upper eyelids and may cause
      visual field restriction or cosmetic blemish for patients. Thus, correct
      diagnosis is important to plan appropriate surgery and obtain a successful
      postoperative result. We present two young patients with lacrimal gland prolapse
      associated with blepharochalasis and report on their treatment. 

PMID- 23543254
TI  - Sublingual misoprostol to reduce blood loss at cesarean delivery.
AB  - OBJECTIVE: This prospective randomized controlled study was carried out with the
      purpose of assessing the efficacy of sublingual misoprostol in decreasing
      intraoperative blood loss and the need for additional uterotonic agents at
      cesarean delivery. METHODS: One hundred seventy-four women undergoing elective or
      emergency cesarean delivery were assigned randomly to receive either 400 MUg
      misoprostol or placebo sublingually at the time of cord clamping. An intravenous
      infusion of 20 units of oxytocin was started in all women at the same time. The
      primary outcome measures were intraoperative blood loss, need for additional
      uterotonic agents, and perioperative hemoglobin (Hb) fall. RESULTS: The maternal
      demographic factors, indications for cesarean delivery, and high-risk factors
      were similar between the two groups. Mean intraoperative blood loss was
      significantly less in misoprostol group as compared with placebo group (595 +/-
      108 vs. 651 +/- 118 ml, P = 0.025). Fewer women needed additional uterotonic
      agents in misoprostol group (22.2 vs. 42.8 %; P = 0.0035; RR 0.52, 95 % CI 0.33
      0.82). Perioperative Hb fall was significantly less in misoprostol group (0.87 +/
      0.29 vs. 1.01 +/- 0.26 g, P = 0.0018). CONCLUSION: Sublingual misoprostol
      decreases intraoperative blood loss and the need for additional uterotonic agents
      at cesarean delivery.

PMID- 23543251
TI  - Generating new neurons to circumvent your fears: the role of IGF signaling.
AB  - Extinction of fear memory is a particular form of cognitive function that is of
      special interest because of its involvement in the treatment of anxiety and mood
      disorders. Based on recent literature and our previous findings (EMBO J
      30(19):4071-4083, 2011), we propose a new hypothesis that implies a tight
      relationship among IGF signaling, adult hippocampal neurogenesis and fear
      extinction. Our proposed model suggests that fear extinction-induced IGF2/IGFBP7
      signaling promotes the survival of neurons at 2-4 weeks old that would
      participate in the discrimination between the original fear memory trace and the
      new safety memory generated during fear extinction. This is also called "pattern
      separation", or the ability to distinguish similar but different cues (e.g.,
      context). To understand the molecular mechanisms underlying fear extinction is
      therefore of great clinical importance. 

PMID- 23543255
TI  - Roles of pectin in biomass yield and processing for biofuels.
AB  - Pectin is a component of the cell walls of plants that is composed of acidic
      sugar-containing backbones with neutral sugar-containing side chains. It
      functions in cell adhesion and wall hydration, and pectin crosslinking influences
      wall porosity and plant morphogenesis. Despite its low abundance in the secondary
      cell walls that make up the majority of lignocellulosic biomass, recent results
      have indicated that pectin influences secondary wall formation in addition to its
      roles in primary wall biosynthesis and modification. This mini-review will
      examine these and other recent results in the context of biomass yield and
      digestibility and discuss how these traits might be enhanced by the genetic and
      molecular modification of pectin. The utility of pectin as a high-value,
      renewable biomass co-product will also be highlighted.

PMID- 23543256
TI  - Comparison of Phenotypic Characterization between Differentiated Osteoblasts from
      Stem Cells and Calvaria Osteoblasts In vitro.
AB  - BACKGROUND: Characteristics of differentiated osteoblasts from adipose derived
      stem cells (ADSCs) in compared with isolated osteoblasts from normal bone such as
      calvaria are unknown. The aim of this study was determination and comparison of
      phenotypic characterization between differentiated osteoblasts from stem cells
      and calvaria osteoblasts in vitro. METHODS: In this study, mesenchymal stem cells
      were isolated from adipose tissue of human by enzymatic digestion and were
      differentiated into osteoblasts using osteogenic medium. Characteristics of these
      cells at first, second, third and fourth weeks were comprised with calvaria
      osteoblasts that were isolated from human calvaria by explanation culture method.
      To screen the characteristics of both calvaria and the differentiated
      osteoblasts, we used western blot to identify protein levels, von Kossa staining
      for mineral matrix detection and alkaline phosphatase (ALP) assay kit (Sigma) for
      ALP activity measurement. Difference between calvaria and differentiated
      osteoblast cells were analyzed by one-way ANOVA and P < 0.05 was considered as
      statistically significant. RESULTS: Alkaline phosphatase activity, collagen and
      mineral material production in differentiated osteoblasts at third week were more
      significantly than calvaria cells (P < 0.05). Our results indicated that there
      was no significant different in osteocalcin (OC) production between
      differentiated osteoblast at first, second and third weeks and calvaria cells but
      declined at fourth week (P < 0.05). CONCLUSIONS: Our survey showed that cellular
      traits of differentiated osteoblasts presented better than calvaria osteoblasts
      in vitro conditions. Therefore, we suggest that ADSCs could be used in next
      studies for bone tissue engineering.

PMID- 23543257
TI  - Modified Double Disc Synergy Test to Detect ESBL Production in Urinary Isolates
      of Escherichia coli and Klebsiella pneumoniae.
AB  - BACKGROUND AND OBJECTIVES: Various phenotypic methods are recommended in the
      routine practice to detect the ESBL production in gram negative bacilli. Among
      them, the Double Disc Synergy Test (DDST) which uses the third generation
      cephalosporins (3GC), is a simple and a reliable method. But the coexistence of
      AmpC may give false negative results. In such cases, the ESBL detection can be
      improved by using cefepime along with the third generation cephalosporins in
      DDST. METHODS: A total of 350 urinary isolates (224 Escherichia coli and 126
      Klebsiella pneumoniae) were studied for ESBL production by the modified double
      disc test (MDDST) i.e. by using cefotaxime, ceftriaxone, cefpopdoxime (third
      generation cephalosporins) and cefepime ( fourth generation cephalosporin) along
      with a amoxicillin-clavulanate disc. RESULTS AND INTERPRETATION: ESBL production
      was seen in 63.4% (142/224) Escherichia coli and in 60.3% (76/126) Klebsiella
      pneumoniae isolates by MDDST. Among these, in twelve E.coli and five K.pneumoniae
      strains, only cefepime but none of the third generation cephalosporins showed
      synergism with amoxicillin-clavulanate. All these seventeen strains showed a
      clear extension of the edge of inhibition which was produced by cefepime towards
      the amoxicillin-clavulanate disc. These strains were further tested for AmpC co
      production by the AmpC disc test and all these strains were found to be AmpC
      positive, thus revealing the superior activity of cefepime in detecting ESBLs in
      the bacteria which co-produced AmpC. A high degree of coresistance was found in
      the ESBL producers. CONCLUSION: The ESBL detection can be improved by MDDST by
      using cefepime along with the third generation cephalosporins.

PMID- 23543258
TI  - Mechanisms of signal transduction by ethylene: overlapping and non-overlapping
      signalling roles in a receptor family.
AB  - The plant hormone ethylene regulates growth and development as well as responses
      to biotic and abiotic stresses. Over the last few decades, key elements involved
      in ethylene signal transduction have been identified through genetic approaches,
      these elements defining a pathway that extends from initial ethylene perception
      at the endoplasmic reticulum to changes in transcriptional regulation within the
      nucleus. Here, we present our current understanding of ethylene signal
      transduction, focusing on recent developments that support a model with
      overlapping and non-overlapping roles for members of the ethylene receptor
      family. We consider the evidence supporting this model for sub-functionalization
      within the receptor family, and then discuss mechanisms by which such a sub
      functionalization may occur. To this end, we consider the importance of receptor
      interactions in modulating their signal output and how such interactions vary in
      the receptor family. In addition, we consider evidence indicating that ethylene
      signal output by the receptors involves both phosphorylation-dependent and
      phosphorylation-independent mechanisms. We conclude with a current model for
      signalling by the ethylene receptors placed within the overall context of
      ethylene signal transduction.

PMID- 23543260
TI  - Evaluation of Luteolin in the Prevention of N-nitrosodiethylamine-induced
      Hepatocellular Carcinoma Using Animal Model System.
AB  - Hepatocellular carcinoma (HCC) is one of the commonest tumors worldwide. The
      treatment of HCC is vital for disease diagnosis and prognosis, as the liver is
      the most important organ controlling metabolic functions. Now-a-days, western
      folklore medicines are largely dependent on the phyto compounds which are highly
      effective in therapy and with low side effects. Luteolin is a flavonoid (3,4,5,7
      Tetrahydro flavones) possess anti-inflammatory, anticancer and anti allergic
      property. The present study evaluates the efficacy of luteolin against N
      nitrosodiethylamine (DEN) induced HCC in albino rats. In the highlight of the
      above, luteolin was evaluated for its efficacy against DEN induced HCC in male
      Wistar albino rats. The Biochemical parameters such as tissue damaging enzymes
      viz., AST, ALP, LDH and gamma-GT, enzymatic antioxidants viz., SOD, CAT, GSH and
      GPx and histopathological changes have been estimated. The tissue damaging
      enzymes were found to be high in DEN alone treated group whereas the enzymatic
      antioxidants decreased destructively. Severe lesions and cirrhosis were observed
      in the toxin (DEN alone) treated group. The luteolin treated DEN group altered
      the tissue damaging enzymes and the enzymatic antioxidants. The damaged lesion in
      the histoarchitecture of DEN treated rat liver was almost completely restored.
      Finally this study strongly demonstrates that luteolin has potent curative
      property against HCC in albino rats.

PMID- 23543259
TI  - Effect of eNOS polymorphisms on salbutamol evoked endothelium dependent
      vasodilation in South Indian healthy subjects.
AB  - BACKGROUND: The model of pulse plethysmograph using inhalational salbutamol 400
      mcg is studied well to assess endothelium dependent vasodilation. Endothelial
      nitric oxide synthase (eNOS) gene polymorphism may influence the response to
      salbutamol in healthy subjects. AIM: To find the effect of polymorphisms 894G>T
      and -786T>C of eNOS gene on endothelium dependent vasodilation in healthy
      subjects. MATERIALS AND METHODS: One hundred and two south Indian healthy
      subjects of either sex, aged between 18 to 35 years were recruited for the study.
      The digital volume pulse (DVP)was measured by pulse plethysmograph before and
      after salbutamol 400mcg inhalation. Three predose and five postdose recordings of
      DVP were measured. The average change in the DVP parameters namely reflection
      index (RI) and stiffness index (SI) were determined. The eNOS894G>T and -786T>C
      gene polymorphism were genotyped using polymerase chain reaction followed by
      restriction fragment length polymorphism. The percentage changes in RI and SI
      from predose baseline recordings were calculated and compared between the
      genotype groups. RESULTS: The genotype and allele frequency of study subjects
      were in Hardy-Weinberg equilibrium. The changes in DVP parameters were not
      significantly different between the genotype groups. CONCLUSION: eNOS
      polymorphism do not affect salbutamol evoked endothelium dependent vasodilation
      in the model of pulse plethysmograph in healthy subjects.

PMID- 23543261
TI  - Fermentative production of shikimic acid: a paradigm shift of production concept
      from plant route to microbial route.
AB  - Different physiological and nutritional parameters affect the fermentative
      production of shikimic acid. In our study, Citrobacter freundii initially
      produced 0.62 g/L of shikimic acid in 72 h. However, when process optimization
      was employed, 5.11 g/L of shikimic acid was produced in the production medium
      consisting of glucose (5.0 %), asparagine (4.5 %), CaCO3 (2.0 %), at pH 6.0, when
      inoculated with 6 % inoculum and incubated at 30 +/- 1  degrees C, 200 rpm for 60
      h. Preliminary fed-batch studies have resulted in the production of 9.11 g/L of
      shikimic acid on feeding the production medium by 20 g/L of glucose at 24 h of
      the fermentation run. Production of similar amount of shikimic acid was observed
      when the optimized conditions were employed in a 10-L bioreactor as obtained in
      shake flask conditions. A total of 9.11 g/L of shikimic acid was produced in 60
      h. This is approximately 14.69-fold increase in shikimic acid production when
      compared to the initial un-optimized production conditions. This has also
      resulted in the reduction of the production time. The present study provides
      useful information to the industrialists seeking environmentally benign
      technology for the production of bulk biomolecules through manipulation of
      various chemical parameters.

PMID- 23543262
TI  - Association between polymorphisms in the TRHR gene, fat-free mass, and muscle
      strength in older women.
AB  - A previous genome-wide association study suggested that polymorphisms in the
      thyrotrophin-releasing hormone receptor (TRHR) gene contribute to fat-free mass
      (FFM) variation. The aim of the present study was to examine the association
      between polymorphisms in the TRHR gene with FFM and muscle strength in older
      women. Volunteers (n = 241; age = 66.65 +/- 5.5 years) underwent quadriceps
      strength assessment using isokinetics and fat-free mass by dual-energy X-ray
      absorptiometry. TRHR polymorphisms and ancestry-informative markers were
      genotyped through standard procedures. No significant difference was observed for
      rs7832552. Regarding the rs16892496, ANCOVA revealed that appendicular fat-free
      mass (AFFM) and relative AFFM were significantly different between groups (p =
      0.04 and p = 0.05, respectively). Individuals carrying A/A and A/C genotypes
      respectively showed, on average, an extra 1 kg and 900 g of AFFM when compared to
      C/C genotype carriers. Also, the C/C genotype group presented a significantly
      higher chance to have reduced muscle strength. The observations presented here
      provide further evidence that the rs16892496 polymorphism in the TRHR gene may
      play a role in FFM variation. Moreover, the results bring the novel insight that
      this genetic variant can present a modest contribution to muscle strength in
      older women.

PMID- 23543263
TI  - Inflammatory markers and incident frailty in men and women: the English
      Longitudinal Study of Ageing.
AB  - Cross-sectional studies show that higher blood concentrations of inflammatory
      markers tend to be more common in frail older people, but longitudinal evidence
      that these inflammatory markers are risk factors for frailty is sparse and
      inconsistent. We investigated the prospective relation between baseline
      concentrations of the inflammatory markers C-reactive protein (CRP) and
      fibrinogen and risk of incident frailty in 2,146 men and women aged 60 to over 90
      years from the English Longitudinal Study of Ageing. The relationship between CRP
      and fibrinogen and risk of incident frailty differed significantly by sex (p for
      interaction terms <0.05). In age-adjusted logistic regression analyses, for a
      standard deviation (SD) increase in CRP or fibrinogen, odds ratios (95%
      confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and
      1.39 (1.12, 1.72), respectively. Further adjustment for other potential
      confounding factors attenuated both these estimates. For an SD increase in CRP
      and fibrinogen, the fully-adjusted odds ratio (95% confidence interval) for
      incident frailty in women was 1.27 (0.96, 1.69) and 1.31 (1.04, 1.67),
      respectively. Having a high concentration of both inflammatory markers was more
      strongly predictive of incident frailty than having a high concentration of
      either marker alone. In men, there were no significant associations between any
      of the inflammatory markers and risk of incident frailty. High concentrations of
      the inflammatory markers CRP and fibrinogen are more strongly predictive of
      incident frailty in women than in men. Further research is needed to understand
      the mechanisms underlying this sex difference.

PMID- 23543264
TI  - Effect of increased fruit and vegetable consumption on physical function and
      muscle strength in older adults.
AB  - Fruit and vegetable (FV) intake, which is often low in older people, may be
      associated with improved muscle strength and physical function. However, there is
      a shortage of intervention trial evidence to support this. The current study
      examined the effect of increased FV consumption on measures of muscle strength
      and physical function among healthy, free-living older adults. A randomized
      controlled intervention study was undertaken. Eighty-three participants aged 65
      85 years, habitually consuming <= 2 portions of FV/day, were randomised to
      continue their normal diet (<= 2 portions/day), or to consume >= 5 portions of
      FV/day for 16 weeks. FV were delivered to all participants each week, free of
      charge. Compliance was monitored at baseline, 6, 12 and 16 weeks by diet history
      and by measuring biomarkers of micronutrient status. Grip strength was measured
      by a hand-held dynamometer, while lower-extremity physical function was assessed
      by performance-based measures. Eighty-two participants completed the
      intervention. The 5 portions/day group showed greater change in daily FV
      consumption compared to the 2 portions/day group (P < 0.001). This was reflected
      in significant increases in biomarkers of micronutrient status. No significant
      differences were evident in change in physical function between the two groups.
      However, there was a trend towards a greater change in grip strength in the 5
      portions/day compared to the 2 portions/day group (mean change at 16 weeks +/-
      SD, 2.04 +/- 5.16 and 0.11 +/- 3.26 kg, respectively, P = 0.06). Increased FV
      consumption may modestly increase grip strength but has no effect on physical
      function in healthy older adults.

PMID- 23543265
TI  - Continuous infusion of vancomycin in neonates.

PMID- 23543266
TI  - Shikimate and phenylalanine biosynthesis in the green lineage.
AB  - The shikimate pathway provides carbon skeletons for the aromatic amino acids l
      tryptophan, l-phenylalanine, and l-tyrosine. It is a high flux bearing pathway
      and it has been estimated that greater than 30% of all fixed carbon is directed
      through this pathway. These combined pathways have been subjected to considerable
      research attention due to the fact that mammals are unable to synthesize these
      amino acids and the fact that one of the enzymes of the shikimate pathway is a
      very effective herbicide target. However, in addition to these characteristics
      these pathways additionally provide important precursors for a wide range of
      important secondary metabolites including chlorogenic acid, alkaloids,
      glucosinolates, auxin, tannins, suberin, lignin and lignan, tocopherols, and
      betalains. Here we review the shikimate pathway of the green lineage and compare
      and contrast its evolution and ubiquity with that of the more specialized
      phenylpropanoid metabolism which this essential pathway fuels.

PMID- 23543267
TI  - Threshold values of physical performance tests for locomotive syndrome.
AB  - BACKGROUND: Our previous study determined which physical performance tests were
      the most useful for evaluating locomotive syndrome. Our current study establishes
      reference values for these major physical performance tests with regards to
      diagnosing and assessing risk of locomotive syndrome (LS). METHODS: We measured
      timed-up-and-go test, one-leg standing time, back muscle strength, grip strength,
      10-m gait time and maximum stride in 406 individuals (167 men, 239 women) between
      the ages of 60-88 years (mean 68.8 +/- 6.7 years) during Yakumo Study 2011-12.
      The LS was defined as having a score of >16 points on the 25-Question Geriatric
      Locomotive Function Scale (GLFS-25). The reference value of each physical test
      was determined using receiver operating characteristics analysis. RESULTS: Women
      had a significantly higher prevalence of LS than men did and also scored
      significantly higher on the GLFS-25: women, 9.2 +/- 10.3 pts; men, 6.7 +/- 8.0
      pts. Both genders in the non-LS group performed significantly better in all
      physical performance test gender except for back muscle strength in men and grip
      strength in both genders than those in the LS group, even after adjusting for
      age. The results of all the physical performance tests correlated significantly
      with the GLFS-25 scores of both genders even after adjusting for age except for
      grip strength. Reference values for TUG, one-leg standing time, back muscle
      strength, 10-m gait time, maximum stride and grip strength in men were 6.7 s, 21
      s, 78 kg, 5.5 s and, 119 cm and 34 kg, respectively, and those for women were 7.5
      s, 15 s, 40 kg, 6.2 s, 104 cm, and 22 kg, respectively. CONCLUSIONS: We
      established reference values for major physical performance tests used when
      assessing locomotive syndrome as defined by the GLFS-25. Our results can be used
      to characterize physical function and to help tailor an anti-LS training program
      for each individual.

PMID- 23543268
TI  - Bevacizumab in the treatment of ovarian cancer: a meta-analysis from four phase
      III randomized controlled trials.
AB  - BACKGROUND: The aim of this meta-analysis was to summarize the efficacy and
      safety of bevacizumab in the treatment of ovarian cancer. METHODS: We sought to
      identify randomised controlled trials (RCTs) by searching PubMed and Web of
      Science. Outcomes were objective response rate (ORR), progression-free survival
      (PFS), overall survival (OS), and adverse events. RESULTS: Four studies with
      4,246 patients were included. Combination of bevacizumab and chemotherapy
      resulted in a statistically significant improvement in ORR (OR 2.165, 95 % CI
      1.511-3.103) and in PFS (HR 0.691, 95 % CI 0.517-0.865), compared with
      chemotherapy alone. There was no evidence of a significant improvement in OS (HR
      0.934, 95 % CI 0.826-1.041). It also had significantly increased risk of
      gastrointestinal events (OR 2.743, 95 % CI 1.580-4.763; P < 0.001), hypertension
      (OR 4.630, 95 % CI 3.737 to 5.737; P < 0.001), proteinuria (OR 4.872, 95 % CI
      2.617-9.069; P < 0.001), and arterial thromboembolism (OR 1.994, 95 % CI 1.210
      3.286; P = 0.007). CONCLUSION: This meta-analysis suggests that the addition of
      bevacizumab to chemotherapy offers meaningful improvement in objective response
      rate and progression-free survival in ovarian cancer treatment, but does not
      benefit overall survival. It also significantly increased the occurrence of
      gastrointestinal events, hypertension, proteinuria, and arterial thromboembolism.

PMID- 23543269
TI  - Coexisting anal human papilloma virus infection in heterosexual women with
      cervical HPV infection.
AB  - AIM: To evaluate the prevalence of coexisting anal human papillomavirus (HPV)
      infection and concordance of HPV types in women with cervical HPV infection and
      to investigate the possible predictors for anal HPV infection. METHODS: Study
      group was composed of women referred with documented cervical HPV infection. All
      patients had undergone anal HPV DNA testing. RESULTS: One hundred and six
      patients presenting with cervical HPV infection were eligible for the study.
      Overall, 24 and 20 distinct HPV genotypes were detected from cervical and anal
      specimens, respectively. We observed a considerably high prevalence (51.9 %) of
      coexisting anal HPV infection in our study group. A majority of the women who
      were found to have anal HPV infection were infected with oncogenic or probable
      oncogenic types (64.6 %). There were 20.0 and 58.3 % rate of total and partial
      concordance between the two sites, respectively. We found that no demographic
      parameter but history of anal intercourse was related with the risk of anal HPV
      infection. CONCLUSION(S): Women with cervical HPV infection have a considerable
      risk for coexisting anal HPV infection. Concordance of HPV types infecting the
      cervix and anal canal is relatively high. There is no strong predictor for anal
      HPV infection in this population.

PMID- 23543270
TI  - Phase I dose-escalation study of EZN-2208 (PEG-SN38), a novel conjugate of
      poly(ethylene) glycol and SN38, administered weekly in patients with advanced
      cancer.
AB  - PURPOSE: This study evaluated the tolerability, pharmacokinetics, and preliminary
      antitumor activity of EZN-2208, a water-soluble poly(ethylene) glycol conjugate
      of SN38. METHODS: Patients with advanced malignancies were enrolled in dose
      escalating cohorts (3 + 3 design). EZN-2208 was administered as a 1-h intravenous
      infusion given weekly for 3 weeks per each 4-week cycle. Doses ranged from 1 to
      12 mg/m(2). RESULTS: Forty-one patients received EZN-2208. All patients had
      received prior cancer therapy (median = 2, range = 1-11). Twenty patients (49 %)
      had received prior irinotecan, and one patient had received prior topotecan. One
      patient in the 9-mg/m(2) cohort had dose-limiting toxicity (grade 3 febrile
      neutropenia), and one patient in the 12-mg/m(2) cohort had grade 3 neutropenia
      that resulted in the inability to deliver the third dose of EZN-2208. The most
      commonly reported drug-related adverse events were nausea (51 %), diarrhea (46
      %), fatigue (41 %), alopecia (29 %), neutropenia (24 %), and vomiting (22 %).
      Administration of EZN-2208 results in prolonged exposure to SN38. Stable disease,
      sometimes prolonged, was observed as best response. CONCLUSIONS: EZN-2208 has an
      acceptable safety profile in previously treated patients with advanced
      malignancies. The recommended phase II dose of EZN-2208 administered according to
      this schedule was 9 mg/m(2).

PMID- 23543271
TI  - A phase I study investigating the safety and pharmacokinetics of highly
      bioavailable curcumin (Theracurmin) in cancer patients.
AB  - BACKGROUND: A growing number of preclinical studies have demonstrated that
      curcumin could be a promising anticancer drug; however, poor bioavailability has
      been the major obstacle for its clinical application. To overcome this problem,
      we developed a new form of curcumin (Theracurmin) and reported high plasma
      curcumin levels could be safely achieved after a single administration of
      Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety
      of repetitive administration of Theracurmin in cancer patients. METHODS:
      Pancreatic or biliary tract cancer patients who failed standard chemotherapy were
      eligible for this study. Based on our previous pharmacokinetic study, we selected
      Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the
      dose was safely escalated to Level 2, which contained 400 mg of curcumin.
      Theracurmin was orally administered every day with standard gemcitabine-based
      chemotherapy. In addition to safety and pharmacokinetics data, NF-kappaB
      activity, cytokine levels, efficacy, and quality-of-life score were evaluated.
      RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak
      plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL
      (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at
      Level 2. No unexpected adverse events were observed and 3 patients safely
      continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive
      systemic exposure to high concentrations of curcumin achieved by Theracurmin did
      not increase the incidence of adverse events in cancer patients receiving
      gemcitabine-based chemotherapy.

PMID- 23543273
TI  - Ornithodoros peropteryx (Acari: Argasidae) in Bolivia: an argasid tick with a
      single nymphal stage.
AB  - By the end of the 1960s, the argasid tick Ornithodoros peropteryx was described
      from larval specimens collected from the bat Peropteryx macrotis in Colombia.
      Since its original description, no additional record of O. peropteryx has been
      reported, and its post-larval stages have remained unknown. During July 2010, 18
      larvae were collected from 9 bats (Centronycteris maximiliani), resulting in a
      mean infestation of 2.0 +/- 2.2 ticks per bat (range 1-8). These bats were
      captured in a farm in northeastern Bolivia close to Guapore River in the border
      with Brazil. Morphological examinations of the larvae revealed them to represent
      the species O. peropteryx. One engorged larva that was kept alive in the
      laboratory moulted to a nymph after 9 days. Fourteen days after the larval
      moulting, the nymph moulted to an adult female without taking any blood meal
      during the nymphal period. This adult female was used for a morphological
      description of the female stage of O. peropteryx. In addition, the larvae were
      used for a morphological redescription of this stage. One larva and two legs
      extirpated from the adult female were submitted to DNA extraction and PCR
      targeting a fragment of the mitochondrial 16S rDNA gene, which yielded DNA
      sequences at least 11 % divergent from any available argasid sequence in Genbank.
      We show that O. peropteryx ontogeny is characterized by a single, non-feeding,
      nymphal stage. This condition has never been reported for ticks.

PMID- 23543272
TI  - Hypoxia-induced expression of VE-cadherin and filamin B in glioma cell cultures
      and pseudopalisade structures.
AB  - Most of our knowledge regarding glioma cell biology comes from cell culture
      experiments. For many years the standards for glioma cell culture were the use of
      cell lines cultured in the presence of serum and 20 % O2. However, in vivo,
      normoxia in many brain areas is in close to 3 % O2. Hence, in cell culture, the
      experimental value referred as the norm is hyperoxic compared to any brain
      physiological value. Likewise, cells in vivo are not usually exposed to serum,
      and low-passaged glioma neurosphere cultures maintained in serum-free medium is
      emerging as a new standard. A consequence of changing the experimental normoxic
      standard from 20 % O2 to the more brain physiological value of 3 % O2, is that a
      3 % O2 normoxic reference point enabled a more rigorous characterization of the
      level of regulation of genes by hypoxia. Among the glioma hypoxia-regulated genes
      characterized using this approach we found VE-cadherin that is required for blood
      vessel formation, and filamin B a gene involved in endothelial cell motility.
      Both VE-cadherin and filamin B were found expressed in pseudopalisades, a
      glioblastoma pathognomonic structure made of hypoxic migrating cancer cells.
      These results provide additional clues on the role played by hypoxia in the
      acquisition of endothelial traits by glioma cells and on the functional links
      existing between pseudopalisades, hypoxia, and tumor progression.

PMID- 23543274
TI  - Chemical attraction of Dermacentor variabilis ticks parasitic to Peromyscus
      leucopus based on host body mass and sex.
AB  - Macroparasites are commonly aggregated on a small subset of a host population.
      Previous explanations for this aggregation relate to differences in
      immunocompetence or the degree to which hosts encounter parasites. We propose
      active tick host choice through chemical attraction as a potential mechanism
      leading to aggregated tick burdens. We test this hypothesis using a Y-maze
      olfactometer, comparing chemical attraction responses of larval and nymphal
      Dermacentor variabilis ticks parasitic to the white-footed mouse, Peromyscus
      leucopus, as a function of host sex and host body mass. We hypothesized that
      larger hosts and male hosts would be most attractive to searching ticks, as these
      hosts commonly have higher tick burdens in the field. Chemical attraction trials
      were run in the presence and absence of a known tick attractant, host-produced
      carbon dioxide (CO2). Male hosts and larger hosts were preferred by nymphal D.
      variabilis in the presence and absence of CO2, whereas larvae had no detectable
      host preference. The current study suggests that host-produced chemical cues may
      promote aggregated tick burdens among hosts of a single species based on host
      body mass and sex.

PMID- 23543277
TI  - Macular hole formation after toxoplasmic retinochoroiditis: coincidence or rare
      complication?

PMID- 23543276
TI  - The unconventional secretion of stress-inducible protein 1 by a heterogeneous
      population of extracellular vesicles.
AB  - The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and
      has important neurotrophic properties upon binding to prion protein (PrP(C)).
      However, STI1 lacks a signal peptide and pharmacological approaches pointed that
      it does not follow a classical secretion mechanism. Ultracentrifugation, size
      exclusion chromatography, electron microscopy, vesicle labeling, and particle
      tracking analysis were used to identify three major types of extracellular
      vesicles (EVs) released from astrocytes with sizes ranging from 20-50, 100-200,
      and 300-400 nm. These EVs carry STI1 and present many exosomal markers, even
      though only a subpopulation had the typical exosomal morphology. The only
      protein, from those evaluated here, present exclusively in vesicles that have
      exosomal morphology was PrP(C). STI1 partially co-localized with Rab5 and Rab7 in
      endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A
      (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and
      STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to
      the outer leaflet of EVs, and its association with EVs greatly increased STI1
      activity upon PrP(C)-dependent neuronal signaling. These results indicate that
      astrocytes secrete a diverse population of EVs derived from MVBs that contain
      STI1 and suggest that the interaction between EVs and neuronal surface components
      enhances STI1-PrP(C) signaling. 

PMID- 23543275
TI  - The BLM dissolvasome in DNA replication and repair.
AB  - RecQ DNA helicases are critical for proper maintenance of genomic stability, and
      mutations in multiple human RecQ genes are linked with genetic disorders
      characterized by a predisposition to cancer. RecQ proteins are conserved from
      prokaryotes to humans and in all cases form higher-order complexes with other
      proteins to efficiently execute their cellular functions. The focus of this
      review is a conserved complex that is formed between RecQ helicases and type-I
      topoisomerases. In humans, this complex is referred to as the BLM dissolvasome or
      BTR complex, and is comprised of the RecQ helicase BLM, topoisomerase IIIalpha,
      and the RMI proteins. The BLM dissolvasome functions to resolve linked DNA
      intermediates without exchange of genetic material, which is critical in somatic
      cells. We will review the history of this complex and highlight its roles in DNA
      replication, recombination, and repair. Additionally, we will review recently
      established interactions between BLM dissolvasome and a second set of genome
      maintenance factors (the Fanconi anemia proteins) that appear to allow
      coordinated genome maintenance efforts between the two systems.

PMID- 23543278
TI  - The role of hand motion connectivity in the performance of laparoscopic
      procedures on a virtual reality simulator.
AB  - Assessment of surgical skills based on virtual reality (VR) technology has
      received major attention in recent years, with special focus placed on experience
      discrimination via hand motion analysis. Although successful, this approach is
      restricted from extracting additional important information about the trainee's
      hand kinematics. In this study, we investigate the role of hand motion
      connectivity in the performance of a laparoscopic cholecystectomy on a VR
      simulator. Two groups were considered: experienced residents and beginners. The
      connectivity pattern of each subject was evaluated by analyzing their hand motion
      signals with multivariate autoregressive (MAR) models. Our analysis included the
      entire as well as key phases of the operation. The results revealed that
      experienced residents outperformed beginners in terms of the number, magnitude
      and covariation of the MAR weights. The magnitude of the coherence spectra
      between different combinations of hand signals was in favor of the experienced
      group. Yet, the more challenging (in terms of hand movement activity) an
      operational phase was, the more connections were generated, with experienced
      subjects performing more coordinated gestures per phase. The proposed approach
      provides a suitable basis for hand motion analysis of surgical trainees and could
      be utilized in future VR simulators for skill assessment. 

PMID- 23543279
TI  - Modelling clavicular and scapular kinematics: from measurement to simulation.
AB  - Musculoskeletal models are intended to be used to assist in prevention and
      treatments of musculoskeletal disorders. To capture important aspects of shoulder
      dysfunction, realistic simulation of clavicular and scapular movements is
      crucial. The range of motion of these bones is dependent on thoracic, clavicular
      and scapular anatomy and therefore different for each individual. Typically,
      patient or subject measurements will therefore not fit on a model that uses a
      cadaveric morphology. Up till now, this problem was solved by adjusting measured
      bone rotations such that they fit on the model, but this leads to adjustments of
      on average 3.98 degrees  and, in some cases, even more than 8 degrees . Two novel
      methods are presented that decrease this discrepancy between experimental data
      and simulations. For one method, the model is scaled to fit the subject, leading
      to a 34 % better fit compared to the existing method. In the other method, the
      set of possible joint rotations is increased by allowing some variation on motion
      constraints, resulting in a 42 % better fit. This change in kinematics also
      affected the kinetics: muscle forces of some important scapular stabilizing
      muscles, as predicted by the Delft Shoulder and Elbow Model, were altered by
      maximally 17 %. The effect on the glenohumeral joint contact force was however
      marginal (1.3 %). The methods presented in this paper might lead to more
      realistic shoulder simulations and can therefore be considered a step towards
      (clinical) application, especially for applications that involve scapular
      imbalance. 

PMID- 23543280
TI  - Nasolacrimal duct obstruction caused by oncocytic carcinoma.
AB  - Here, we report an extremely rare case of acquired nasolacrimal duct obstruction
      caused by oncocytic carcinoma. A 64-year-old man presented to the hospital
      complaining of epiphora and left-side nasal obstruction. Ophthalmic and
      otolaryngology examination revealed a left lacrimal duct obstruction caused by a
      mass in the left nasal cavity and lacrimal drainage system. The mass was removed
      and confirmed as an oncocytic carcinoma. Nine months after surgery, without
      adjuvant radiotherapy, a left orbital mass was observed and the patient underwent
      reoperation. The mass proved to be recurrent oncocytic carcinoma. The patient
      underwent adjuvant radiotherapy to eradicate any residual tumor and the patient
      remains tumor-free one year post-radiotherapy.

PMID- 23543281
TI  - The mini-Kingston Standardized Cognitive Assessment.
AB  - The Kingston Standardized Cognitive Assessment (KSCA) was designed to be a
      cognitive screening tool available for the health professionals who were not
      trained in specialized cognitive assessment techniques. It was introduced to
      bridge the gap between brief, narrowly focused rating scales and intensive,
      expensive, full neuropsychological assessments. We now present the mini-KSCA
      Revised (mini-KSCAr). This is a shortened version of the full KSCAr that can be
      given in far less time and allows for a quick follow-up or screening technique
      retaining a substantial part of the full KSCAr's effectiveness. It is
      specifically targeted for use by family physicians who require rapid and accurate
      in-office dementia screening.

PMID- 23543282
TI  - Diagnosis of heart failure with preserved ejection fraction: role of clinical
      Doppler echocardiography.

PMID- 23543283
TI  - Relationship between optical coherence tomography derived intraluminal and
      intramural criteria and haemodynamic relevance as determined by fractional flow
      reserve in intermediate coronary stenoses of patients with type 2 diabetes.
AB  - BACKGROUND: The relationship between functional relevance and optical coherence
      tomography (OCT)-derived measurements of coronary lesions is incompletely
      understood and of critical importance, particularly in cardiovascular high-risk
      patients with type 2 diabetes. OBJECTIVE: To investigate the association between
      functional relevance of intermediate grade coronary stenoses as assessed by
      fractional flow reserve (FFR) and OCT-derived lesion parameters in patients with
      diabetes. METHODS: In 46 diabetic patients with stable coronary artery disease,
      FFR and OCT were performed in 62 coronary lesions with intermediate severity as
      determined by quantitative coronary angiography. Among lesions haemodynamic
      relevance was defined as FFR<=0.8. RESULTS: There was a significant association
      between FFR and OCT-derived minimal lumen area (r(2)=0.379) and minimal lumen
      diameter (r(2)=0.268), all p<0.001. Receiver operating curve (ROC)-analysis
      demonstrated an OCT-derived minimal lumen area <1.59 mm(2) and minimal lumen
      diameter <1.31 mm to be optimal cut-off values to predict FFR<=0.8. Furthermore,
      in lipid-rich plaques FFR was significantly associated with minimal fibrous cap
      thickness (FCT, r(2)=0.399). Minimal FCT in lesions with FFR<=0.8 was
      significantly smaller (60.7+/-15.0 um) compared with those lesions with FFR>0.8
      (106.0+/-13.0 um, p<0.001). ROC-analysis revealed that 0.81 is the ideal FFR cut
      off to identify lesions with a minimal FCT<=80 um (accuracy 97.3%, sensitivity
      100%, specificity 93.8%, area under the curve 0.943 (95% CI 0.836 to 1.000)).
      CONCLUSIONS: Haemodynamic relevance of intermediate grade lesions in patients
      with type 2 diabetes is closely related to (1) intraluminal measurements, which
      are smaller than previously described in non-diabetic cohorts and to (2) minimal
      FCT. Furthermore, FFR may be useful to identify vulnerable (minimal FCT<=80 um)
      lesions among those with intermediate severity in lipid-rich plaques.

PMID- 23543284
TI  - Euro-NOTES Status Paper: from the concept to clinical practice.
AB  - BACKGROUND: The concept of natural orifice transluminal endoscopic surgery
      (NOTES) consists of the reduction of access trauma by using a natural orifice
      access to the intra-abdominal cavity. This could possibly lead to less
      postoperative pain, quicker recovery from surgery, fewer postoperative
      complications, fewer wound infections, and fewer long-term problems such as
      hernias. The Euro-NOTES Foundation has organized yearly meetings to work on this
      concept to bring it safely into clinical practice. The aim of this Euro-NOTES
      status update is to assess the yearly scientific working group reports and
      provide an overview on the current clinical practice of NOTES procedures.
      METHODS: After the Euro-NOTES meeting 2011 in Frankfurt, Germany, an analysis was
      started regarding the most important topics of the European working groups. All
      prospectively documented information was gathered from Euro-NOTES and D-NOTES
      working groups from 2007 to 2011. The top five topics were analyzed. RESULTS: The
      statements of the working group activities demonstrate the growing information
      and changing insights. The most important selected topics were infection issue,
      peritoneal access, education and training, platforms and new technology, closure,
      suture, and anastomosis. The focus on research topics changed over time. The
      principle of hybrid access has overcome the technical and safety limitations of
      pure NOTES. Currently the following NOTES access routes are established for
      several indications: transvaginal access for cholecystectomy, appendectomy and
      colon resections; transesophageal access for myotomy; transgastric access for
      full-thickness small-tumor resections; and transanal/transcolonic access for
      rectal and colon resections. CONCLUSIONS: NOTES and hybrid NOTES techniques have
      emerged for all natural orifices and were introduced into clinical practice with
      a good safety record. There are different indications for different natural
      orifices. Each technique has been optimized for the purpose of finding a safe and
      realistic solution to perform the procedure according to the specific indication.

PMID- 23543286
TI  - A case of resistant schizophrenia responding at a higher than recommended dose of
      risperidone without significant side effects.
AB  - A patient, diagnosed with schizophrenia, non-responsive to two atypical
      antipsychotics and partially responsive to the third (risperidone) in therapeutic
      dose, ultimately showed complete response without any unacceptable side-effect in
      a dose (20 mg) that was untried previously. This case makes an important
      observation that high dose of risperidone can be tried in a patient with good
      results if his clinical condition permits.

PMID- 23543285
TI  - Development and Aging of the Kisspeptin-GPR54 System in the Mammalian Brain: What
      are the Impacts on Female Reproductive Function?
AB  - The prominent role of the G protein coupled receptor GPR54 and its peptide ligand
      kisspeptin in the progression of puberty has been extensively documented in many
      mammalian species including humans. Kisspeptins are very potent gonadotropin
      releasing hormone secretagogues produced by two main populations of neurons
      located in two ventral forebrain regions, the preoptic area and the arcuate
      nucleus. Within the last 2 years a substantial amount of data has accumulated
      concerning the development of these neuronal populations and their timely
      regulation by central and peripheral factors during fetal, neonatal, and
      peripubertal stages of development. This review focuses on the development of the
      kisspeptin-GPR54 system in the brain of female mice, rats, sheep, monkeys, and
      humans. We will also discuss the notion that this system represents a major
      target through which signals from the environment early in life can reprogram
      reproductive function.

PMID- 23543287
TI  - Oil-bioremediation potential of two hydrocarbonoclastic, diazotrophic
      Marinobacter strains from hypersaline areas along the Arabian Gulf coasts.
AB  - Two halophilic, hydrocarbonoclastics bacteria, Marinobacter sedimentarum and M.
      flavimaris, with diazotrophic potential occured in hypersaline waters and soils
      in southern and northern coasts of Kuwait. Their numbers were in the magnitude of
      10(3) colony forming units g(-1). The ambient salinity in the hypersaline
      environments was between 3.2 and 3.5 M NaCl. The partial 16S rRNA gene sequences
      of the two strains showed, respectively, 99 and 100% similarities to the
      sequences in the GenBank. The two strains failed to grow in the absence of NaCl,
      exhibited best growth and hydrocarbon biodegradation in the presence of 1 to 1.5
      M NaCl, and still grew and maintained their hydrocarbonoclastic activity at
      salinities up to 5 M NaCl. Both species utilized Tween 80, a wide range of
      individual aliphatic hydrocarbons (C9-C40) and the aromatics benzene, biphenyl,
      phenanthrene, anthracene and naphthalene as sole sources of carbon and energy.
      Experimental evidence was provided for their nitrogen-fixation potential. The two
      halophilic Marinobacter strains successfully mineralized crude oil in nutrient
      media as well as in hypersaline soil and water microcosms without the use of any
      nitrogen fertilizers.

PMID- 23543288
TI  - In vitro assessment of the acaricidal activity of computer-selected analogues of
      carvacrol and salicylic acid on Rhipicephalus (Boophilus) microplus.
AB  - Rhipicephalus (Boophilus) microplus is a tick that causes huge economic losses in
      cattle. The indiscriminate use of acaricides has generated resistance to most
      compounds present on the market. This makes further investigation on other
      potential acaricides necessary, the in silico assay being an alternative to the
      design of new compounds. In the present study a biosilico assay was performed
      using TOMOCOMD-CARDD (TOpological MOlecular COMputer Design-Computer-Aided
      Rational Drug Design) and WEKA (Waikato Environment for Knowledge Analysis)
      software. Two carvacrol and four salicylic acid derivatives, synthesized by
      conventional methods and evaluated with the larval packet test on larvae of R.
      (B.) microplus were selected. All evaluated compounds presented acaricidal
      activity; however, ethyl 2-methoxybenzoate (91.8 +/- 1.7 % mortality) and ethyl
      2,5-dihydroxybenzoate (89.1 +/- 1.6 % mortality) showed greater activity than
      salicylic acid. With regard to the carvacrol analogues, carvacrol acetate (67.8
      +/- 2.1 % mortality) and carvacrol methyl ether (71.7 +/- 1.6 % mortality) also
      showed greater activity than carvacrol (35.9 +/- 3.2 % mortality). TOMOCOMD-CARDD
      and WEKA software were helpful tools in the search for alternative structures
      with potential acaricidal activity on R. (B.) microplus.

PMID- 23543289
TI  - Bromodomains as therapeutic targets in cancer.
AB  - The malleability of the epigenome has long been recognized as a unique
      opportunity for therapeutic intervention. Interest in targeting components of the
      epigenetic machinery for therapeutic gain had initially been aimed at chromatin
      modifying enzymes. However, advances in medicinal chemistry have now made it
      possible to exploit protein-protein interactions at the chromatin interface.
      Bromodomains (BRD) are a conserved motif used by a large number of chromatin
      associated proteins to recognize and bind acetylated histone tails. Small
      molecules with high specificity for the Bromodomain and Extra Terminal family of
      proteins (BRD2, BRD3, BRD4 and BRDT) have recently been shown to have remarkable
      pre-clinical efficacy in various malignancies. These findings have provided the
      impetus for exploring other BRD proteins as novel targets in cancer therapy.

PMID- 23543290
TI  - Migration and geographical inequalities in health in the Netherlands: an
      investigation of age patterns.
AB  - OBJECTIVES: This paper estimates, for six different age groups, whether and how
      migration influences inequalities in health between deprived and non-deprived
      neighbourhoods in the Netherlands. METHODS: Data were accessed from the
      Netherlands Housing Survey 2006. Using multi-level logistic regression analyses,
      we compared the health of migrants with that of nonmigrants in the area of origin
      and assessed the role of demographic and socioeconomic characteristics. Next, we
      assessed the magnitude of health differences between deprived versus non-deprived
      areas among migrants and non-migrants. RESULTS: For many age groups, migrants
      into non-deprived areas were healthier and migrants into deprived areas had
      similar levels of health compared with non-migrant populations in the area of
      origin. These differences in health were not explained by demographic and socio
      economic characteristics. For all ages and for people aged 25-34 years we found
      smaller area inequalities in health among migrants compared with non-migrants.
      For most other age groups, about equally large differences were observed.
      CONCLUSIONS: For most age groups, the results do not provide empirical support to
      the expectation that migration would enlarge health differences between deprived
      and non-deprived neighbourhoods.

PMID- 23543291
TI  - Brief report: atypical neuromagnetic responses to illusory auditory pitch in
      children with autism spectrum disorders.
AB  - Atypical auditory perception is a widely recognised but poorly understood feature
      of autism. In the current study, we used magnetoencephalography to measure the
      brain responses of 10 autistic children as they listened passively to dichotic
      pitch stimuli, in which an illusory tone is generated by sub-millisecond inter
      aural timing differences in white noise. Relative to control stimuli that contain
      no inter-aural timing differences, dichotic pitch stimuli typically elicit an
      object related negativity (ORN) response, associated with the perceptual
      segregation of the tone and the carrier noise into distinct auditory objects.
      Autistic children failed to demonstrate an ORN, suggesting a failure of
      segregation; however, comparison with the ORNs of age-matched typically
      developing controls narrowly failed to attain significance. More striking, the
      autistic children demonstrated a significant differential response to the pitch
      stimulus, peaking at around 50 ms. This was not present in the control group, nor
      has it been found in other groups tested using similar stimuli. This response may
      be a neural signature of atypical processing of pitch in at least some autistic
      individuals. 

PMID- 23543292
TI  - A review of technology-based interventions to teach academic skills to students
      with autism spectrum disorder.
AB  - A comprehensive review of the literature was conducted for articles published
      between 1993 and 2012 to determine the degree to which technology-based
      interventions can be considered an evidence-based practice to teach academic
      skills to individuals with Autism Spectrum Disorder (ASD). Criteria developed by
      Horner et al. (Except Child 71:165-178, 2005) and Gersten et al. (Except Child
      71:149-164, 2005) were used to determine the quality of single-subject research
      studies and group experimental research studies respectively. A total of 29
      [Corrected] studies met inclusion criteria. Of these studies, only three single
      subject studies and no group studies met criteria for quality or acceptable
      studies. Taken together, the results suggest that practitioners should use
      caution when teaching academic skills to individuals with ASD using technology
      based interventions. Limitations and directions for future research are
      discussed.

PMID- 23543293
TI  - Sensitivity and specificity of proposed DSM-5 criteria for autism spectrum
      disorder in toddlers.
AB  - Autism spectrum disorder (ASD) diagnosis is based on behavioral presentation;
      changes in conceptual models or defining behaviors may significantly impact
      diagnosis and uptake of ASD-specific interventions. The literature examining
      impact of DSM-5 criteria is equivocal. Toddlers may be especially vulnerable to
      the stringent requirements of impairment in all three social-communication
      symptoms and two restricted/repetitive symptoms. Receiver operating
      characteristic (ROC) curves identified optimal cutoffs for sums of ADOS and ADI-R
      criteria mapped to each criterion for 422 toddlers. The optimal modification of
      DSM-5 criteria (sensitivity = 0.93, specificity = 0.74) required meeting the ROC
      determined cutoffs for 2/3 Domain A criteria and 1 point for 1/4 Domain B
      criteria. This modification will help insure that ASD is identified accurately in
      young children, facilitating ASD-specific early intervention.

PMID- 23543294
TI  - A phase II study evaluating the feasibility of a 5-week cycle of S-1 plus
      irinotecan (IRIS) in patients with advanced and recurrent colorectal cancer.
AB  - PURPOSE: A number of clinical trials, including the FIRIS study, have shown that
      S-1 plus irinotecan (IRIS) is safe and effective in patients with colorectal
      cancer. Several different treatment protocols for IRIS are commonly used in
      Japan, besides the one used in the FIRIS study. This study was designed to
      evaluate the feasibility of a 5-week cycle of IRIS. METHODS: Between January 2005
      and February 2008, a total of 55 patients with metastatic colorectal cancer were
      enrolled at nine centers in Japan. All patients received irinotecan intravenously
      (80 mg/m(2)) on days 1 and 15 and S-1 orally (40-60 mg twice daily, according to
      body surface area) on days 1-21 of a 5-week repeated cycle. RESULTS: The overall
      response rate was 29.1 %. The response rate was 43.8 % in patients who received
      IRIS as first-line therapy and 23.1 % in those who received IRIS as second-line
      or subsequent therapy. The median survival time was 678 days (22.6 months).
      Adverse events of Grade 3 or higher that occurred at an incidence of >=10 % were
      neutropenia (12.7 %) and diarrhea (10.9 %). CONCLUSION: Our efficacy and safety
      data suggest that a 5-week cycle of IRIS is an effective alternative to used
      currently regimens.

PMID- 23543295
TI  - Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing
      chemotherapy in colorectal cancer.
AB  - PURPOSE: Oxaliplatin or irinotecan is usually administered jointly with
      fluoropyrimidines in colorectal cancer patients treated with chemotherapy. Both
      drugs have different toxicity patterns. Biomarkers for predicting high-risk
      severe adverse reactions can help select the best treatment. METHODS: A
      retrospective analysis of 106 colorectal cancer patients receiving an oxaliplatin
      based treatment and 56 receiving an irinotecan-based treatment was performed. One
      copy number variant (GSTT1) and nine polymorphisms in irinotecan and oxaliplatin
      metabolism, transport or DNA repair genes (ABCB1, UGT1A1, XRCC1, ERCC1, ERCC2,
      GSTP1) were genotyped by SNaPshot, polymerase chain reactions' length fragments,
      or copy number assays. RESULTS: In irinotecan-treated patients, T allele of
      ABCB1C1236T SNP was associated with a lower risk of asthenia(OR = 0.047; 95 % CI
      = 0.004-0.493; P = 0.011) and Tallele of ABCB1 C3435T SNP was associated with a
      lower risk of diarrhea (OR = 0.177; 95 % CI = 0.034-0.919;P = 0.039), and
      individuals with two copies of GSTT1 gene had a lower risk for asthenia (OR =
      0.093; 95 %CI = 0.011-0.794; P = 0.030). In oxaliplatin-treated patients,
      carriers of one or two T variants of Asn118Asn ERCC1 SNP had a lower risk for
      neutropenia(OR = 0.205; 95 % CI = 0.061-0.690; P = 0.01) [corrected].
      CONCLUSIONS: These biomarkers could help oncologists select the best treatment by
      reducing toxicity associated with irinotecan or oxaliplatin in colorectal cancer
      patients, thus increasing their quality of life.

PMID- 23543296
TI  - Subclinical pretreatment sensory deficits appear to predict the development of
      pain and numbness in patients with multiple myeloma undergoing chemotherapy.
AB  - PURPOSE: Chemotherapy-induced peripheral neuropathy is a major complication in
      the treatment for cancer, including multiple myeloma (MM). Patients may develop
      painful and non-painful (e.g., numbness) neuropathy symptoms that impair function
      and often persist after therapy is terminated. This study tested the hypothesis
      that baseline subclinical neuropathy, as assessed by sensory thresholds, is
      related to the development of neuropathy symptoms (e.g., pain and numbness) in
      patients with MM undergoing treatment with chemotherapy. METHODS: Patients (n =
      56) who had undergone two or fewer cycles of induction therapy and who had no
      evident neuropathy were assessed using quantitative sensory tests to determine
      multiple-modality sensory thresholds. Patient-reported pain and numbness were
      assessed through induction therapy (16 weeks) via the MD Anderson Symptom
      Inventory. A subset of participants (n = 15) continued reporting on their
      symptoms for an additional 16 weeks ("maintenance phase"). RESULTS: Patients with
      sharpness detection deficits at baseline (n = 11, 20 % of sample) reported less
      severe pain and numbness during induction therapy and less numbness during
      maintenance therapy (P < 0.05). During the maintenance phase, patients with
      warmth detection deficits (n = 5, 38 % of sample) reported more severe pain and
      numbness, and those with skin temperature deficits (n = 7, 47 % of maintenance
      sample) reported more severe pain (P < 0.05). These deficits were related to
      patient reported difficulty walking, a common symptom of peripheral neuropathy.
      CONCLUSION: Our results suggest that baseline subclinical sensory deficits may be
      related to a patient's risk for developing chemotherapy-induced peripheral
      neuropathy.

PMID- 23543297
TI  - Cytopathology of parasitic dermatitis in dogs.
AB  - Out of 44 cases of dermatitis in dogs, 11 cases of parasitic origin were analyzed
      by cytopathology. Histopathologic examination of punch biopsies was also done for
      correlation with cytologic findings. Sarcoptic dermatitis was recorded in six
      cases, wherein, besides sarcoptic mites, neutrophils, macrophages, and plasma
      cells and keratinizing epithelial cells were also seen. Hematology revealed a
      relative neutrophilia and mild eosinophilia. Four cases of severe and generalized
      demodicosis complicated with bacteria and/or Malassezia sp. infection were also
      recorded. Histopathologically numerous Demodex sp. mites in varying stage of
      maturation were found damaging the hair follicles along with associated
      pathological changes and foreign body granulomas in one case. In addition, flea
      allergy dermatitis was also observed in one dog. In nutshell, cytology was found
      to be unequivocally effective in diagnosing parasitic dermatitis.

PMID- 23543298
TI  - Melanoma of the ear: results of a cartilage-sparing approach to resection.
AB  - Melanoma of the ear is often treated by composite resection of the skin and
      cartilage and, occasionally, by total auriculectomy. This review analyzes the
      oncologic, functional, and esthetic results of cartilage-sparing wide local
      excision for melanoma of the ear. This retrospective study reviewed patients with
      ear melanoma treated between 1997 and 2002. All patients were treated with
      cartilage-sparing wide local excision, and ears were reconstructed with skin
      grafts and/or local flaps. The majority of patients were men (16/18 patients) who
      ranged in age from 42 to 82 years. The most common sites of occurrence were the
      helical rim (7/18 patients) and the earlobe (6/18 patients). The average depth of
      invasion was 2.02 mm (range 0.4-6.0 mm). Sentinel lymph node biopsy was performed
      in 13 cases, of which only one was positive. The local control rate was 100 %,
      overall survival was 72 % (13/18 patients), and disease-specific survival was 89
      % (16/18 patients). Average follow-up was 30.5 months (range 1-61). The rates for
      local control, overall survival, and disease-specific survival were excellent.
      These data indicate that for the majority of ear melanomas, cartilage-sparing
      wide local excision is an acceptable means of treatment. 

PMID- 23543299
TI  - Serum vitamin D levels in children with recurrent otitis media.
AB  - The aims of this study were to evaluate serum vitamin D levels in cases of
      recurrent otitis media and investigate the effect of vitamin D therapy on the
      risk of re-occurrence of the disease. This prospective study was performed by
      comparing serum vitamin D levels in children with recurrent otitis media and
      healthy children. Eighty-four children between 1 and 5 years of age and diagnosed
      with recurrent otitis media were enrolled as the study group. One hundred-and
      eight healthy children with similar demographic characteristics were enrolled as
      the control group. Patients were divided into groups according to their serum
      25(OH) vitamin D levels. In patients with low initial serum vitamin D levels,
      vitamin D therapy was administered in addition to conventional treatment for
      otitis media. Mean serum 25(OH) vitamin D level in the study group was 11.4 +/-
      9.8 ng/mL Serum 25(OH) vitamin D levels were below 20 ng/mL in 69 % (n = 58) of
      cases in this group. In the control group, mean serum 25(OH) vitamin D level was
      29.2 +/- 13.9 ng/mL and was below 20 ng/mL in 30 % (n = 32) of cases. Comparison
      of serum 25(OH) vitamin D levels and PTH in the study and control groups revealed
      a statistically significant difference (p < 0.05). Treatment was initiated in
      cases diagnosed with vitamin D deficiency, and patients were followed up in due
      course. The only episodes detected over the course of 1-year follow-up were one
      attack in five patients and two attacks in two. We believe that co-administration
      of supplementary vitamin D together with conventional treatments is appropriate
      in the management of upper respiratory infections such as otitis media.

PMID- 23543300
TI  - Repositioning of the caudal septal dislocations with notching and suturing the
      cartilage to the nasal spine.
AB  - We aim to define a cartilage reshaping and repositioning technique for caudal
      septal dislocations, with the logic of adapting the smoother tissues to the
      stiffer structures. The study was designed retrospectively with the patient
      charts and photographic analysis. Thirty-six patients who had septal surgery in a
      septoplasty or an open approach septorhinoplasty operation and meet the inclusion
      criteria were evaluated for the study. Postoperative success of the technique was
      based on preoperative and postoperative photographic analysis by two independent
      otorhinolaryngologists. The estimators classified 33 cases as near complete, 3
      cases as improved but persisting caudal septal deviation, and any cases with no
      change. The improvement of the degree of reconstruction was near complete about
      87% in septoplasty and 95% in septorhinoplasty groups, and 92% for all patients.
      In this study, we present a caudal septal repositioning maneuver which achieves a
      stable anchorage between postero-caudal septal cartilage and nasal spine. Septal
      cartilage is notched and fixed to nasal spine with two simple independent sutures
      as lock and key model. We define this maneuver as riding spine technique. It is
      an anatomic re-orientation between the septum and nasal spine for caudal septal
      deviations and subluxations.

PMID- 23543301
TI  - Enhanced transfection by antioxidative polymeric gene carrier that reduces
      polyplex-mediated cellular oxidative stress.
AB  - PURPOSE: To test the hypothesis in which polyplex-induced oxidative stress may
      affect overall transfection efficiency, an antioxidative transfection system
      minimizing cellular oxidative stress was designed for enhanced transfection.
      METHODS: An amphiphilic copolymer (PEI-PLGA) was synthesized and used as a
      micelle-type gene carrier containing hydrophobic antioxidant, alpha-tocopherol.
      Cellular oxidative stress and the change of mitochondrial membrane potential
      after transfection was measured by using a fluorescent probe (H2DCFDA) and
      lipophilic cationic probe (JC-1), respectively. Transfection efficiency was
      determined by measuring a reporter gene (luciferase) expression level. RESULTS:
      The initial transfection study with conventional PEI/plasmid DNA polyplex showed
      significant generation of reactive oxygen species (ROS). The PEI-PLGA copolymer
      successfully carried out the simultaneous delivery of alpha-tocopherol and
      plasmid DNA (PEI-PLGA/Toco/pDNA polyplex) into cells, resulting in a significant
      reduction in cellular ROS generation after transfection and helped to maintain
      the mitochondrial membrane potential (DeltaPsi). In addition, the transfection
      efficiency was dramatically increased using the antioxidative transfection
      system. CONCLUSIONS: This work showed that oxidative stress would be one of the
      important factors that should be considered in designing non-viral gene carriers
      and suggested a possible way to reduce the carrier-mediated oxidative stress,
      which consequently leads to enhanced transfection.

PMID- 23543302
TI  - Non-aqueous suspensions of antibodies are much less viscous than equally
      concentrated aqueous solutions.
AB  - PURPOSE: The aim of this study was to markedly lower the viscosities of highly
      concentrated protein, in particular antibody, formulations. An effective approach
      elaborated herein for gamma-globulin and a monoclonal antibody is to replace
      aqueous solutions with equimolar suspensions in neat organic solvents. METHODS:
      Viscosities of aqueous solutions and non-aqueous suspensions of the model protein
      bovine gamma-globulin and a murine monoclonal antibody were examined under a
      variety of experimental conditions. In addition, protein particle sizes were
      measured using dynamic light scattering and light microscopy. RESULTS:
      Concentrated suspensions of amorphous gamma-globulin powders (up to 300 mg/mL,
      composed of multi-micron-sized particles) in absolute ethanol and a number of
      other organic solvents were found to have viscosities up to 38 times lower than
      the corresponding aqueous solutions. Monoclonal antibody follows the same general
      trend. Additionally, the higher the protein concentration and lower the
      temperature, the greater the viscosity benefit of a suspension over a solution.
      CONCLUSIONS: The viscosities of concentrated gamma-globulin and monoclonal
      antibody suspensions in organic solvents are drastically reduced compared to the
      corresponding aqueous solutions; the magnitude of this reduction depends on the
      solvent, particularly its hydrogen-bonding properties.

PMID- 23543303
TI  - Design of biorelevant test setups for the prediction of diclofenac in vivo
      features after oral administration.
AB  - PURPOSE: Design of biorelevant test setups mimicking the physiological conditions
      experienced by drugs after oral administration along the passage through the
      mouth and the GI tract for the in vitro evaluation of diclofenac exhibiting
      multiple-peak phenomenon during absorption. METHODS: The biorelevant models
      simulated successively saliva (SSF, pH 6.2-6.75-7.4, 5 mL, 3 min), gastric (SGF
      FaSSGF, pH 1.2-1.6, 50-250 mL, 30 min) and intestinal (FaSSIF, pH 6.8, 250 mL, 60
      min) fluids. Applying these models, diclofenac free acid and its sodium/potassium
      salt were comparatively evaluated for dissolution and further characterized by
      HPLC, optical morphogranulometry, DSC and PXRD to elucidate peculiar behaviors.
      RESULTS: Diclofenac salts almost completely dissolved in SSF and showed a
      transitional dissolution pattern before complete precipitation in SGF/FaSSGF.
      This peculiar pattern correlated with simultaneous chemical modification and
      formation of agglomerates. With low dissolution in SSF and almost immediately
      complete precipitation, these behaviors were not observed with diclofenac free
      acid. Distinct diclofenac features were strongly determined by pH-modifications
      after oral administration. CONCLUSIONS: The multiple-peak phenomenon observed
      after administrating a solution, suspension or dispersible formulation of
      diclofenac salts are likely caused by drug precipitation and agglomeration in the
      stomach leading to irregular gastric-emptying. Diclofenac free acid may provide
      more reliable in vivo features.

PMID- 23543304
TI  - A physiologically based pharmacokinetic model for strontium exposure in rat.
AB  - PURPOSE: To develop a physiologically based pharmacokinetic (PBPK) model to
      describe the disposition of Strontium--a bone seeking agent approved in 2004 (as
      its Ranelate salt) for treatment of osteoporosis in post-menopausal women.
      METHODS: The model was developed using plasma and bone exposure data obtained
      from ovariectomised (OVX) female rats--a preclinical model for post-menopausal
      osteoporosis. The final PBPK model incorporated elements from literature models
      for bone seeking agents allowing for description of the heterogeneity of bone
      tissue and also for a physiological description of bone remodelling processes.
      The model was implemented in MATLAB in open and closed loop configurations, and
      fittings of the model to exposure data to estimate certain model parameters were
      carried out using nonlinear regression, treating data with a naive-pooled
      approach. RESULTS: The PBPK model successfully described plasma and bone exposure
      of Strontium in OVX rats with parameter estimates and model behaviour in keeping
      with known aspects of the distribution and incorporation of Strontium into bone.
      CONCLUSIONS: The model describes Strontium exposure in a physiologically
      rationalized manner and has the potential for future uses in modelling the PK-PD
      of Strontium, and/or other bone seeking agents, and for scaling to model human
      Strontium bone exposure.

PMID- 23543305
TI  - Cranial translation of the humeral head on radiographs in rotator cuff tear
      patients: the modified active abduction view.
AB  - Cranial translation of the humeral head is related to massive rotator cuff tears;
      however, it may be unapparent in early-stage tears. The goal of this study was to
      investigate whether active abduction leads to increased active cranial humeral
      translation in early-stage tears. We assessed 20 consecutive patients (9 full
      thickness supraspinatus tears, 11 posterosuperior tears) using the newly
      introduced modified active abduction view: acromiohumeral (AH) distance was
      measured on radiographs acquired during rest and active isometric abduction and
      adduction tasks with the arm alongside the body. Rest AH was 7.5 mm (SD = 1.53);
      during abduction and adduction, it decreased to 2.1 mm (95 % CI 1.28-3.01, p <
      0.001) and 1.1 mm (95 % CI 0.46-1.65, p = 0.001), respectively. Cranial
      translation during abduction was more severe in shoulders with posterosuperior
      cuff tears (?AH = 3 mm, SD = 1.5) compared to supraspinatus tears (?AH = 1 mm, SD
      = 1.6), with a mean difference of 2 mm (95 % CI 0.64-3.58, p = 0.007). Both
      active isometric abduction and adduction leads to active cranial translation in
      cuff tear patients. Cranial translation is largest during active abduction.
      Furthermore, there is significant more cranial translation in posterosuperior
      cuff tear patients compared to supraspinatus cuff tear patients. Possibly,
      radiographs combined with active tasks offer new possibilities in diagnosing
      early-stage rotator cuff tears. 

PMID- 23543306
TI  - Monitoring respiration in wheezy preschool children by pulse oximetry
      plethysmogram analysis.
AB  - The aim of this study was to investigate whether respiratory information can be
      derived from pulse oximetry plethysmogram (pleth) recordings in acutely wheezy
      preschool children. A digital pulse oximeter was connected via 'Bluetooth' to a
      notebook computer in order to acquire pleth data. Low pass filtering and
      frequency analysis were used to derive respiratory rate from the pleth trace; the
      ratio of heart rate to respiratory rate (HR/RR) was also calculated. Recordings
      were obtained during acute wheezy episodes in 18 children of median age 31 months
      and follow-up recordings from 16 of the children were obtained when they were
      wheeze-free. For the acutely wheezy children, frequency analysis of the pleth
      waveform was within 10 breaths/min of clinical assessment in 25 of 29 recordings
      in 15 children. For the follow-up measurements, frequency analysis of the pleth
      waveform showed similarly good agreement in recordings on 15 of the 16 children.
      Respiratory rate was higher (p < 0.001), and HR/RR ratio was lower (p = 0.03)
      during acute wheeze than at follow-up. This study suggests that respiratory rate
      can be derived from pleth traces in wheezy preschool children.

PMID- 23543307
TI  - Obsolete ideas and logical confusions can be obstacles for biogerontology
      research.
AB  - Some misconceptions can be an obstacle for biogerontology research. These
      misconceptions can be classified in two categories: (1) obsolete ideas in
      biology, for example "aging has a universal cause" and "living beings are like
      machines", and (2) conceptual and logical confusions, such as "longevity is not
      dependent on other life-history traits", "between-groups variability allows to
      infer conclusions about individual variability", and "the burden of the proof
      lies with the opponents to the hypothesis". This opinion article describes these
      problems in the hope it will help to overcome them.

PMID- 23543308
TI  - Roma coronary heart disease patients have more medical risk factors and greater
      severity of coronary heart disease than non-Roma.
AB  - OBJECTIVES: Coronary heart disease (CHD) is the most common cause of mortality
      and morbidity world-wide. Evidence on ethnic differences between the Roma and non
      Roma regarding medical risk factors is scarce. The aim of this study was to
      assess differences in medical risk factors and the severity of CHD in Roma
      compared with non-Roma CHD patients, adjusted for gender, age and education.
      METHODS: Six hundred seventy four patients were included in this cross-sectional
      study (132 Roma, 542 non-Roma). Data on medical risk factors, symptoms,
      medication and severity of CHD were obtained from medical records. After matching
      Roma and non-Roma according to education, linear and logistic regression analyses
      with adjustments for gender and age were used. RESULTS: Compared with non-Roma,
      Roma patients had significantly more risk factors and more severe types of CHD.
      They were treated less frequently with statins and beta-blockers, were more
      frequently left on pharmacotherapy and surgically revascularised. These
      differences remained after controlling for education, gender and age.
      CONCLUSIONS: Roma CHD patients have a worse risk profile at entry of care and
      seem to be undertreated compared with non-Roma CHD patients.

PMID- 23543309
TI  - Modeling the role of altruism of antibiotic-resistant bacteria.
AB  - Based on the new findings in a recent experimental study (Lee et al., Nature 467,
      82-86, 2010) that antibiotic resistant mutants of bacteria produce indoles to
      protect the wild strain bacteria, we propose a mathematical model to describe the
      evolution of the wild strain, resistant strain and indoles with limited nutrient.
      We distinguish two cases: (i) mutation is negligible and a resistant strain
      preexists; (ii) mutation is not negligible. For (i), we establish conditions for
      co-persistence of both strains, which indicate that the wild strain can survive
      with the help from the altruistic resistant strain, whereas it dies out in the
      absence of such a benefit. This consolidates the experimental findings in Lee et
      al. (Nature 467:82-86 2010). Further analysis and simulations also reveal some
      new phenomena not reported in Lee et al. (Nature 467:82-86 2010), that is,
      periodic oscillations of the populations may occur within certain range of the
      parameters, and there exists bistability in the sense that a stable positive
      periodic solution coexists with a stable positive equilibrium. 

PMID- 23543310
TI  - A simple mathematical model of gradual Darwinian evolution: emergence of a
      Gaussian trait distribution in adaptation along a fitness gradient.
AB  - We consider a simple mathematical model of gradual Darwinian evolution in
      continuous time and continuous trait space, due to intraspecific competition for
      common resource in an asexually reproducing population in constant environment,
      while far from evolutionary stable equilibrium. The model admits exact analytical
      solution. In particular, Gaussian distribution of the trait emerges from generic
      initial conditions. 

PMID- 23543311
TI  - Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of
      peginterferon alfa-2a +/- ribavirin for chronic hepatitis C of Genotype 1b: a
      multicenter randomized trial, ReGIT-J study.
AB  - BACKGROUND: We conducted a multicenter randomized clinical trial to determine the
      optimal treatment strategy against chronic hepatitis C virus (HCV) with genotype
      1b and a high viral load (G1b/high). METHODS: The study subjects included 153
      patients with G1b/high. Patients were initially treated with PEG-IFNalpha-2a
      alone and then randomly assigned to receive different treatment regimens.
      Ribavirin (RBV) was administered to all patients with HCV RNA at week 4. Patients
      negative for HCV RNA at week 4 were randomly assigned to receive PEG-IFNalpha-2a
      (group A) or PEG-IFNalpha-2a/RBV (group B). Patients who showed HCV RNA at week 4
      but were negative at week 12 were randomly assigned to receive weekly PEG
      IFNalpha-2a (group C) or biweekly therapy (group D). Patients who showed HCV RNA
      at week 12 but were negative at week 24 were randomly assigned to receive PEG
      IFNalpha-2a/RBV (group E) or PEG-IFNalpha-2a/RBV/fluvastatin (group F). RESULTS:
      Overall, the rate of sustained virological response (SVR) was 46 % (70/153). The
      total SVR rate in the group (A, D, and F) of response-guided therapy was
      significantly higher than that in the group (B, C, and E) of conventional therapy
      [70 % (38/54) versus 52 % (32/61), p = 0.049]. Although IL28-B polymorphism and
      Core 70 mutation were significantly associated with efficacy, patients with rapid
      virological response (RVR) and complete early virological response (cEVR)
      achieved high SVR rates regardless of their status of IL-28B polymorphism and
      Core 70 mutation. CONCLUSION: In addition to knowing the IL-28B polymorphism and
      Core 70 mutation status, understanding the likelihood of virological response
      during treatment is critical in determining the appropriate treatment strategy.

PMID- 23543312
TI  - Mitochondrial metabolism in the noncancerous liver determine the occurrence of
      hepatocellular carcinoma: a prospective study.
AB  - BACKGROUND: Recurrence determines the postoperative prognosis with hepatocellular
      carcinoma (HCC). It is unknown how the liver dysfunction involving organic anion
      transporter failure causes the occurrence of HCCs. This study was designed to
      elucidate the link between liver dysfunction and multicentric occurrence (MO)
      after radical hepatectomy. METHODS: Forty-nine samples of noncancerous liver
      tissue from HCC patients within the Milan criteria who were treated at our
      institution between January 2004 and August 2008 were examined as a training set
      by using genome-wide gene expression analysis. Using the independent 2
      institutional cohort of 134 patients between September 2008 and December 2009, we
      performed a validation study using tissue microarray analysis. Cox proportional
      hazard regression analyses for MFS were performed to estimate the risk factors.
      RESULTS: In the Gene Ontology database (GO:0015711), SLC22A7 expression was the
      best predictor of MO-free survival [MFS] (Fold, 0.726; P = 0.001). High SLC22A7
      gene expression prevented the occurrence of HCC after hepatectomy (odds ratio
      [OR], 0.2; P = 0.004). Multivariate analyses identified SLC22A7 expression as an
      independent risk factor (OR, 0.3; P = 0.043). In the validation study,
      multivariate analyses of MFS identified SLC22A7 expression as an independent risk
      factor (OR, 0.5; P = 0.012). As judged by gene set enrichment analysis, SLC22A7
      down regulation was associated with mitochondrion (P = 0.008) and oxidoreductase
      activity (P = 0.006). Sirtuin 3 as a regulator of mitochondrial metabolism also
      determined MFS (P = 0.018). CONCLUSIONS: The mitochondrial pathways may affect
      SLC 22A7 function to promote the occurrence of HCC. (Word count: 246).

PMID- 23543313
TI  - Beneficial effects of green tea catechin on massive hepatectomy model in rats.
AB  - BACKGROUND: Green tea catechin, especially epigallocatechin gallate (EGCG), is a
      well-known scavenger of reactive oxygen species and it may also function as an
      antioxidant through modulation of transcriptional factors and enzyme activities.
      METHODS: Green tea extract (GTE(r)) which contained numerous EGCG was used.
      Wistar rats were performed 90 % hepatectomy and classified into 2 groups with
      (GTEHx, n = 25) or without GTE treatment (Hx, n = 25) and sacrificed at 1, 3, 7
      and 14 days after operations. All rats had free access to drinking water
      supplemented with or without GTE from the 7th pre-operative day. Liver
      regeneration, hepatic inducible nitric oxide synthase (iNOS), anti-oxidative
      enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH
      Px)] and inflammatory markers [cyclooxygenase-2 (COX-2), nuclear factor kappa B
      (NFkappaB), tumor necrosis factor-alpha (TNF-alpha)] were investigated. RESULTS:
      The liver weight to body weight ratio (p < 0.01), proliferating cell nuclear
      antigen labeling index (p < 0.05) and phosphorylated extracellular signal
      regulated kinase 1/2 (p < 0.05) at day 1 in the GTEHx group significantly
      increased compared to the Hx group. Hepatic iNOS levels at day 1 significantly
      decreased (p < 0.01) in the GTEHx group. Hepatic SOD, CAT and GSH-Px levels at
      day 1 significantly increased (SOD: p < 0.01, CAT and GSH-Px: p < 0.05) in the
      GTEHx group. In contrast, COX-2, NFkappaB and TNF-alpha levels at day 1
      significantly decreased (COX-2: p < 0.01, NFkappaB and TNF-alpha: p < 0.05) in
      the GTEHx group. CONCLUSIONS: GTE pretreatment stimulated liver regeneration and
      improved liver damage after massive hepatectomy through anti-oxidative and anti
      inflammatory effects. Green tea catechin might have the potential to attenuate
      liver dysfunction in early stage after massive hepatectomy.

PMID- 23543314
TI  - Serum HBV RNA as a possible marker of HBV replication in the liver during
      nucleot(s)ide analogue therapy.

PMID- 23543315
TI  - Negative and positive illness representations of rheumatoid arthritis: a latent
      profile analysis.
AB  - This study extends previous work to consider whether individuals with rheumatoid
      arthritis (RA) can be categorised into groups with similar illness
      representations. Data from 227 RA patients attending outpatient clinics were
      collected prospectively at two time points, 6 months apart. The optimal number of
      illness representation groups at the baseline assessment was identified using
      latent profile analysis. Two groups of individuals sharing similar illness
      perception profiles were identified. The smaller group (43%), characterised by a
      negative representation of their illness, attributed more symptoms to their
      condition and reported stronger perceptions of the consequences, chronicity and
      cyclicality of their condition, and lower control compared to the positive
      representation group (57%). Cross-sectionally, membership of the negative
      representation group was associated with higher levels of pain and functional
      disability and, longitudinally, with increases in levels of pain, functional
      disability and distress. These data highlight the central role of illness
      perceptions in RA and suggest that individuals with RA can be categorised into
      groups with similar illness representations.

PMID- 23543316
TI  - Acanthosis Nigricansin PCOS Patients and Its Relation with Type 2 Diabetes
      Mellitus and Body Mass at a Tertiary Care Hospital in Southern India.
AB  - BACKGROUND: Acanthosis nigricansis was viewed recently as a possible marker of an
      increased risk for diabetes. Acanthosis Nigricans (AN) can help in identifying
      the patients with an increased risk for Type 2 Diabetes Mellitus (T2DM) among
      Polycystic Ovary Syndrome (PCOS) cases. Hence, this study was carried to know the
      prevalence of AN in PCOS and its correlation with diabetes mellitus and the body
      mass. METHODS: A prospective, longitudinal study in the patients with PCOS, who
      attended the Department of Medicine, Kasturba Medical College [KMC] Hospital,
      Attavar, Mangalore, Karnatka, India between December 2008 to April 2010, was
      carried out. A total of 119 patients with PCOS were included in the study. A
      complete history, along with the demographic data of the patients who were aged
      between 15-35 years, were considered for the analysis. RESULTS: AN was observed
      in 56% of the PCOS patients. The Body Mass Index (BMI) and the waist
      circumference were significantly higher in the PCOS patients with AN, as compared
      to those without AN. Among the 119 PCOS patients,77% were found to have BMI
      values which were above the normal. Among the obese PCOS patients, 58% had BMI
      values of more than 30kg/m(2) as compared to 19% of the patients who did not have
      AN. Type 2 DM was observed in 77% of the PCOS patients with AN, while none of the
      PCOS patients were found to be diabetic among those without AN. A family history
      of DM in the first degree relatives was present in all the patients with AN. The
      results were analyzed by the Mann Whitney U test for the continuous data and by
      the Chi square test for the categorical data. CONCLUSION: The PCOS patients who
      had a family history of diabetes and obesity with a body mass index of more than
      30 kg/m(2) and a waist circumference of >= 90 cm were more likely to develop AN,
      which is a marker of hyperinsulinaemia and insulin resistance. Identifying such
      PCOS patients will stimulate the discussions of the lifestyle modifications in
      the primary care setting.

PMID- 23543317
TI  - Gluteal and perianal hidradenitis suppurativa associated with tuberulosis.
AB  - Perineal and gluteal hidradenitis suppurativa is a rare, chronic inflammatory
      disease of the skin caused by concomitant occlusion of the apocrine glands. We
      present a case report of a young male with no co-morbid conditions in which
      histopathology and DNA PCR showed association of chronic hyderadenitis
      suppurativa with tuberculosis. There was relapse after three months of completion
      of anti tubercular therapy. He was subsequently treated successfully with wide
      excision, split thickness skin grafting and a defunctioning stoma.

PMID- 23543318
TI  - Conformational heterogeneity within the LID domain mediates substrate binding to
      Escherichia coli adenylate kinase: function follows fluctuations.
AB  - Proteins exist as dynamic ensembles of molecules, implying that protein amino
      acid sequences evolved to code for both the ground state structure as well as the
      entire energy landscape of excited states. Accumulating theoretical and
      experimental evidence suggests that enzymes use such conformational fluctuations
      to facilitate allosteric processes important for substrate binding and possibly
      catalysis. This phenomenon can be clearly demonstrated in Escherichia coli
      adenylate kinase, where experimentally observed local unfolding of the LID
      subdomain, as opposed to a more commonly postulated rigid-body opening motion, is
      related to substrate binding. Because "entropy promoting" glycine mutations
      designed to increase specifically the local unfolding of the LID domain also
      affect substrate binding, changes in the excited energy landscape effectively
      tune the function of this enzyme without changing the ground state structure or
      the catalytic site. Thus, additional thermodynamic information, above and beyond
      the single folded structure of an enzyme-substrate complex, is likely required
      for a full and quantitative understanding of how enzymes work. 

PMID- 23543319
TI  - Priorities of head and neck cancer patients: a patient survey based on the brief
      ICF core set for HNC.
AB  - The International Classification of Functioning, Disability and Health Core Set
      for Head and Neck Cancer (ICF-HNC) covers the typical spectrum of problems in
      functioning experienced by patients with head and neck cancer (HNC). The major
      goal of the present work was to evaluate patients' priorities using the brief ICF
      HNC as a starting point. A priorities assessment checklist consisting of 15
      statements was created based on the 14 validated categories of the brief ICF-HNC.
      In a cross-sectional study, patients were requested to select up to 5 items that
      were especially important to them. The checklist was sent by mail to 465 patients
      at different time points of cancer follow-up and handed out to 56 patients with
      recent HNC diagnosis. Altogether 300 (64.51 %) patients returned the checklist.
      The top priority of our sample was "I want to survive the cancer", followed by "I
      want that all the expenses for cancer treatment, cancer care and any additional
      follow-up treatments be covered by my health insurance or by the welfare system",
      "I want to be able to continue performing all daily life tasks well", "I want to
      have trusting relationships with my doctors, nurses and therapists" and "I want
      to be able to speak clearly". Although survival was, as expected, the top
      priority for patients enrolled in the study, we show that the weight given to
      survival and further symptoms or daily life activities meaningfully changes when
      the biopsychosocial perspective proposed in the ICF is adopted.

PMID- 23543320
TI  - Early one-stage surgical treatment of infected preauricular sinus.
AB  - The objective of this study was to review outcomes of early one-stage surgery of
      acutely infected preauricular sinus compared to conventional delayed surgery
      after infection control. The study is a case series with chart review conducted
      in an academic center. From January 1, 2007 to January 31, 2012, we performed
      surgical treatments for 136 congenital preauricular sinuses on 103 patients aged
      0-15 years. We classified the sinuses according to the state of their infection
      at the time of the surgery intraoperatively--Group I (asymptomatic; n = 68, 50
      %), Group II (infected state; n = 26, 19 %) and Group III (infected state with
      abscess formation; n = 42, 31 %). The surgical outcomes of Groups I, II, and III
      were documented during an outpatient department observation period. The follow-up
      period was from 6 months to over 2 years. One patient from Group II and one
      patient from Group III had a recurrent infection which could be managed by local
      infection control. One patient from Group I and one patient from Group III had
      skin defects by necrosis of a skin flap margin which could be secondarily healed.
      All patients had no recurrence or significant chronic complications. We performed
      early one-stage surgical treatments on a total of 136 sinuses with an even acute
      infection with abscess formation and achieved good surgical outcomes, and
      patients were satisfied in aspects of treatment period and cost. So we present
      our early one-stage surgical treatment as a good option for infected preauricular
      sinus management.

PMID- 23543322
TI  - Computer-aided focal liver lesion detection.
AB  - PURPOSE: Our aim is to develop an automatic method which can detect diverse focal
      liver lesions (FLLs) in 3D CT volumes. METHOD: A hybrid generative-discriminative
      framework is proposed. It first uses a generative model to describe non-lesion
      components and then identifies all candidate FLLs within a 3D liver volume by
      eliminating non-lesion components. It subsequently uses a discriminative approach
      to suppress false positives with the advantage of tumoroid, a novel measurement
      combining three shape features spherical symmetry, compactness and size. RESULTS:
      This method was tested on 71 abdominal CT datasets (5,854 slices from 61
      patients, with 261 FLLs covering six pathological types) and evaluated using the
      free-response receiver operating characteristic (FROC) curves. Overall, it
      achieved a true positive rate of 90 % with one false positive per liver. It
      degenerated gently with the decrease in lesion sizes to 30 ml. It achieved a true
      positive rate of 36 % when tested on the lesions less than 4 ml. The average
      computing time of the lesion detection is 4 min and 28 s per CT volume on a PC
      with 2.67 GHz CPU and 4.0 GB RAM. CONCLUSIONS: The proposed method is comparable
      to the radiologists' visual investigation in terms of efficiency. The tool has
      great potential to reduce radiologists' burden in going through thousands of
      images routinely.

PMID- 23543321
TI  - RNAi silencing of three homologues of S-adenosylmethionine decarboxylase gene in
      tapetal tissue of tomato results in male sterility.
AB  - Polyamines play very important role in various cellular metabolic functions,
      including floral induction, floral differentiation and fertility regulation. In
      the present study, S-adenosylmethionine decarboxylase (SAMDC), a key gene
      involved in polyamine biosynthesis, has been targeted in tapetal tissue of tomato
      using RNAi to examine its effect on tapetum development and pollen viability. The
      target SAMDC gene fragments of three homologues were cloned in a hairpin RNA
      construct under the control of tapetal-specific A9 promoter, which was used to
      generate several RNAi tomato plants. These RNAi lines expressed the intended
      small interfering RNAs in the anther and showed the aborted and sterile pollen
      exhibiting shrunken and distorted morphology. These RNAi tomato plants having
      sterile pollen, failed to set fruits but female fertility of the plants remained
      unaffected as cross pollination resulted in fruit setting. Expression profiling
      of SAMDC genes showed considerable decrease in transcripts of SAMDC1 (5-8 fold)
      and SAMDC2 and SAMDC3 (2-3 fold) in the anthers of RNAi plants. The other
      polyamine biosynthesis genes, ADC and SPDSYN exhibited ~1.5 fold decrease in
      their transcript levels. Presence of siRNA molecules specific to SAMDC homologues
      in anther and tapetal-specific activity of A9 promoter as shown with GUS reporter
      system of RNAi plants suggested down-regulation of the target genes in tapetum by
      RNAi. These observations indicate the importance of SAMDC, in turn polyamines in
      pollen development, and thus tapetum-specific down-regulation of SAMDC genes
      using RNAi can be used for developing male sterile plants.

PMID- 23543323
TI  - Hybrid electromagnetic and image-based tracking of endoscopes with guaranteed
      smooth output.
AB  - PURPOSE: Flexible fiber-optic bronchoscopy is a widespread medical procedure for
      the diagnosis and treatment of lung diseases. Navigation systems are needed to
      track the flexible endoscope within the bronchial tree. Electromagnetic (EM)
      tracking is currently the only technology used clinically for this purpose. The
      registration between EM tracking and patient anatomy may become inaccurate due to
      breathing motion, so the addition of image-based tracking has been proposed as a
      hybrid EM-image-based system. METHODS: When EM tracking is used as an
      initialization for image registration, small changes in the initialization may
      lead to different local minima and noise is amplified by hybrid tracking. The
      tracking output is modeled as continuous and uses splines for interpolation, thus
      smoothness is greatly improved. The bronchoscope pose relative to computed
      tomography data is interpolated using Catmull-Rom splines for position and
      spherical linear interpolation (SLERP) for orientation. RESULTS: The hybrid
      method was evaluated using ground truth poses manually selected by experts, where
      mean inter-expert agreement was determined as 1.26 mm. Using four dynamic phantom
      data sets, the accuracy was 4.91 mm, which is equivalent to previous methods.
      Compared to state-of-art methods, inter-frame smoothness was improved from 2.77
      3.72 to 1.24 mm. CONCLUSIONS: Hybrid image and electromagnetic endoscope guidance
      provides a more realistic and physically plausible solution with significantly
      less jitter. This quantitative result is confirmed by visual comparison of real
      and virtual video, where the virtual video output is much more consistent and
      robust, with fewer occasions of tracking loss or unexpected movement compared
      with previous methods.

PMID- 23543324
TI  - Enzymatic synthesis of glutathione using engineered Saccharomyces cerevisiae.
AB  - Two single gene cassettes, each containing one of the individual gene (gamma
      glutamylcysteine synthetase gene GSH1 or glutathione synthetase gene GSH2), were
      constructed under the control of alcohol dehydrogenase (ADH1) promoter and their
      respective native terminators. The recombinant plasmids constructed with Kan (r)
      or Hyg (r) as the selective markers and were transformed into Saccharomyces
      cerevisiae separately and jointly. Three engineered strains, GSH1-enhanced strain
      S.TS013/GSH1, GSH2-enhanced strain S.TS013/GSH2 and GSH1+GSH2 double-enhanced
      strain S.TS013/GSH1+GSH2, were constructed. Glutathione production using the
      recombinant strains to improve was then determined. By the cell dosage
      proportions of two engineered strains (S.TS013/GSH1, S.TS013/GSH2) and a two
      stage reaction, GSH productivity increased by 84 and 59 % over that of the host
      strain and the S.TS013/GSH1+GSH2 strain, respectively.

PMID- 23543325
TI  - Pancreatic involvement in Japanese patients with von Hippel-Lindau disease:
      results of a nationwide survey.
AB  - BACKGROUND: The frequency and prognosis of pancreatic endocrine tumors
      (PNET)/pancreatic cystic tumors (PCT) in Japanese patients with von Hippel-Lindau
      disease (VHL) are still open to question. METHODS: We conducted the first
      nationwide epidemiological study of VHL disease in Japan to elucidate this
      question. Data on 377 VHL patients (PNET, 53; PCT, 152) were reported, and then
      their clinical characteristics were analyzed. RESULTS: PNET was found in 14.1 %
      and PCT in 40.3 %; 4.5 % had both. The onset of PNET and PCT mostly occurred at
      30-39 years of age (median ages, 34 and 33 years, respectively). Metastasis was
      observed in 7.5 % of PNET patients at diagnosis, and 64.2 % underwent surgery
      including enucleation, partial and total pancreatectomy, and bypass surgery. Two
      patients received non-surgical therapies. No PNET-related deaths were observed.
      In PCT patients, no metastasis was observed at diagnosis, and 9.2 % underwent
      surgery or drainage. According to the classification system without or with
      adrenal pheochromocytoma, the VHL patients studied herein were subdivided into
      313 (83 %) with VHL type 1 and 64 (17 %) with VHL type 2; 29 (9.3 %) and 24 (37.5
      %) patients had PNET with VHL type 1 and 2, suggesting that patients with VHL
      type 2 were significantly more related to PNET than those with VHL type 1 (P <
      0.01). CONCLUSIONS: This study showed no significant difference in the
      epidemiology of pancreatic involvement between Japanese and non-Japanese VHL
      patients. Concerning the prognosis, follow-up study is needed.

PMID- 23543326
TI  - Sorafenib enhances proteasome inhibitor-induced cell death via inactivation of
      Akt and stress-activated protein kinases.
AB  - BACKGROUND: Advanced hepatocellular carcinoma (HCC) responds poorly to
      conventional systemic therapies. Therefore, new effective therapy strategies are
      urgently needed. Molecular targeted therapies have entered the field of anti
      neoplastic treatment and are being used on their own and in combination with
      other drugs. Sorafenib inhibits proliferation and angiogenesis of HCC by
      suppressing the Raf serine/threonine kinases and the receptor tyrosine kinases.
      The proteasome inhibitor bortezomib has shown activity in a variety of solid
      tumors, including HCC. However, the precise anti-proliferative mechanisms of
      these agents remain unclear. METHODS: We treated human hepatoma cell lines (Huh7
      and Hep3B) and immortalized human hepatocyte (OUMS29) with sorafenib and/or
      proteasome inhibitors, including epoxomicin and acetyl-leucyl-leucyl-norleucinal.
      Cytotoxic effects were examined by morphometric analyses of apoptosis and
      necrosis. Apoptosis was also evaluated by Western blotting of keratin18, PARP and
      caspase3. The activity of Akt and stress-activated protein kinases was examined
      by Western blotting. RESULTS: Both sorafenib and proteasome inhibitors induced
      apoptosis in Huh7 and OUMS29. However, sorafenib attenuated proteasome inhibitor
      induced apoptosis. Sorafenib induced necrosis, especially in combination with
      proteasome inhibitors. Sorafenib induced down-regulation of Akt synergistically
      in combination with proteasome inhibitors in Huh7. Sorafenib inhibited both the
      JNK and p38 pathways in a time- and dose-dependent manner. In addition, sorafenib
      also inhibited proteasome inhibitor-mediated JNK and p38 activation in both Huh7
      and OUMS29. CONCLUSIONS: Sorafenib enhances the anti-proliferative effect of
      proteasome inhibitors in part by inactivating the Akt signaling pathway and
      modulating stress-activated protein kinases. The combination of these agents
      could be an ideal molecular targeted therapy for HCC.

PMID- 23543327
TI  - Pulmonary function in ankylosing spondylitis: association with clinical
      variables.
AB  - To evaluate the association between pulmonary function and clinical variables in
      ankylosing spondylitis (AS) and to compare the pulmonary function of patients
      with AS with that of healthy controls, 61 AS patients and 74 healthy controls
      were included. In AS, we assessed clinical disease indices (BASDAI, BASFI, BASG),
      morning stiffness, number of hypersensitive entheses, metrology measures, 6-min
      walking test, acute phase reactants, radiological presence of "bamboo spine," and
      severity of radiological involvement in sacroiliac and vertebral joints. AS and
      healthy controls had similar age and gender. All the parameters of pulmonary
      function were significantly diminished in AS than in healthy controls (p <
      0.001), with a higher proportion of restrictive pattern (57.4 vs. 5.4 %). In AS,
      pulmonary function correlated negatively with BASDAI, BASFI, BASG, morning
      stiffness, number of hypersensitive entheses, occiput-wall distance, and ESR, and
      positively with 6-min walking test. There was no association between pulmonary
      function with radiological stage of vertebral joints and sacroiliac joints,
      "bamboo spine," disease duration, or chest expansion. A higher frequency of AS
      patients had a decreased pulmonary function and results of the 6-min walking
      test. These abnormalities in AS were more related with disease activity than with
      mobility limitation.

PMID- 23543328
TI  - Integrating mental health services into a general hospital in Puerto Rico.
AB  - The prevalence of mental health problems in the general population should be
      carefully considered. The literature has reported a high co-morbidity of medical
      and mental illnesses; therefore, collaborative efforts incorporating
      psychological services into medical settings are imperative. In Puerto Rico, this
      is not a regular practice in general hospitals. Improving access to mental health
      services is a challenge and requires the creation of new venues within the
      healthcare system. This paper describes the theoretical framework, mission, and
      objectives of the Clinical Psychology Services Program (CPSP) implemented at
      Damas Hospital in Puerto Rico. From December 2002 to December 2010, a total of
      13,580 visits were made to inpatients in diverse clinical units of the hospital;
      61% of all inpatients evaluated met the criteria for at least one mental health
      disorder based on the DSM-IV-TR. The CPSP's outcomes highlight the acceptance and
      relevance of incorporating mental health services and clinical psychologists into
      general hospitals.

PMID- 23543329
TI  - Imidazolium or guanidinium/layered manganese (III, IV) oxide hybrid as a
      promising structural model for the water-oxidizing complex of Photosystem II for
      artificial photosynthetic systems.
AB  - Photosystem II is responsible for the light-driven biological water-splitting
      system in oxygenic photosynthesis and contains a cluster of one calcium and four
      manganese ions at its water-oxidizing complex. This cluster may serve as a model
      for the design of artificial or biomimetic systems capable of splitting water
      into oxygen and hydrogen. In this study, we consider the ability of manganese
      oxide monosheets to self-assemble with organic compounds. Layered structures of
      manganese oxide, including guanidinium and imidazolium groups, were synthesized
      and characterized by scanning electron microscopy, transmission electron
      microscopy, X-ray diffraction spectrometry, and atomic absorption spectroscopy.
      The compounds can be considered as new structural models for the water-oxidizing
      complex of Photosystem II. The overvoltage of water oxidation for the compounds
      in these conditions at pH = 6.3 is ~0.6 V. These compounds may represent the
      first step to synthesize a hybrid of guanidinium or imidazole together with
      manganese as a biomimetic system for the water-oxidizing complex of Photosystem
      II. 

PMID- 23543330
TI  - Can phenotypic plasticity in Rubisco performance contribute to photosynthetic
      acclimation?
AB  - Photosynthetic acclimation varies among species, which likely reveals variations
      at the biochemical level in the pathways that constitute carbon assimilation and
      energy transfer. Local adaptation and phenotypic plasticity affect the
      environmental response of photosynthesis. Phenotypic plasticity allows for a wide
      array of responses from a single individual, encouraging fitness in a broad
      variety of environments. Rubisco catalyses the first enzymatic step of
      photosynthesis, and is thus central to life on Earth. The enzyme is well
      conserved, but there is habitat-dependent variation in kinetic parameters,
      indicating that local adaptation may occur. Here, we review evidence suggesting
      that land plants can adjust Rubisco's intrinsic biochemical characteristics
      during acclimation. We show that this plasticity can theoretically improve CO2
      assimilation; the effect is non-trivial, but small relative to other acclimation
      responses. We conclude by discussing possible mechanisms that could account for
      biochemical plasticity in land plant Rubisco. 

PMID- 23543331
TI  - Maintaining photosynthetic CO2 fixation via protein remodelling: the Rubisco
      activases.
AB  - The key photosynthetic, CO2-fixing enzyme Rubisco forms inactivated complexes
      with its substrate ribulose 1,5-bisphosphate (RuBP) and other sugar phosphate
      inhibitors. The independently evolved AAA+ proteins Rubisco activase and CbbX
      harness energy from ATP hydrolysis to remodel Rubisco complexes, facilitating
      release of these inhibitors. Here, we discuss recent structural and mechanistic
      advances towards the understanding of protein-mediated Rubisco activation. Both
      activating proteins appear to form ring-shaped hexameric arrangements typical for
      AAA+ ATPases in their functional form, but display very different regulatory and
      biochemical properties. Considering the thermolability of the plant enzyme, an
      improved understanding of the mechanism for Rubisco activation may help in
      developing heat-resistant plants adapted to the challenge of global warming. 

PMID- 23543332
TI  - Use of antibiotic prophylaxis in elective inguinal hernia repair in adults in
      London and south-east England: a cross-sectional survey.
AB  - PURPOSE: Evidence regarding whether or not antibiotic prophylaxis is beneficial
      in preventing post-operative surgical site infection in adult inguinal hernia
      repair is conflicting. A recent Cochrane review based on 17 randomised trials did
      not reach a conclusion on this subject. This study aimed to describe the current
      practice and determine whether clinical equipoise is prevalent. METHODS: Surgeons
      in training were recruited to administer the Survey of Hernia Antibiotic
      Prophylaxis usE survey to consultant-level general surgeons in London and the
      south-east of England on their practices and beliefs regarding antibiotic
      prophylaxis in adult elective inguinal hernia repair. Local prophylaxis
      guidelines for the participating hospital sites were also determined. RESULTS:
      The study was conducted at 34 different sites and received completed surveys from
      229 out of a possible 245 surgeons, a 93 % response rate. Overall, a large
      majority of hospital guidelines (22/28) and surgeons' personal beliefs (192/229,
      84 %) supported the use of single-dose pre-operative intravenous antibiotic
      prophylaxis in inguinal hernia repair, although there was considerable variation
      in the regimens in use. The most widely used regimen was intravenous co-amoxiclav
      (1.2 g). Less than half of surgeons were adherent to their own hospital
      antibiotic guidelines for this procedure, although many incorrectly believed that
      they were following these. CONCLUSION: In the south-east of England, there is a
      strong majority of surgical opinion in favour of the use of antibiotic
      prophylaxis in this procedure. It is therefore likely to be extremely difficult
      to conduct further randomised studies in the UK to support or refute the
      effectiveness of prophylaxis in this commonly performed procedure.

PMID- 23543333
TI  - Survey of post-operative instructions after inguinal hernia repair in England in
      2012.
AB  - INTRODUCTION: The annual cost of employee absences from work to UK business is
      estimated to be L32 billion, with routine post-operative recovery time being the
      second commonest reason for employee absence. We surveyed what post-operative
      instructions are currently being given to patients by surgeons after inguinal
      hernia repair in England. METHODS: Acute trusts were emailed in England asking
      for leaflets and patients information regarding inguinal hernia repair under the
      Freedom of Information Act (2000). RESULTS: A total of 128 (89.5 %) trusts
      replied. Leaflets were returned by 93 (65%) trusts. After inguinal hernia repair,
      the time to return to work varied widely according to office work (range 1-6
      weeks) and manual labour work (range 2-12 weeks). The time advised to return to
      driving ranged from 24 h to 6 weeks. The time advised before allowing sexual
      activities ranged from 1 to 4 weeks and return to sports ranged from 2 to 12
      weeks after hernia repair. CONCLUSION: Surgeons and trusts should be able to
      provide patients with printed consistent and accurate information regarding their
      post-operative recovery time, including return to driving and return to work.

PMID- 23543334
TI  - Early report of a randomized comparative clinical trial of StratticeTM
      reconstructive tissue matrix to lightweight synthetic mesh in the repair of
      inguinal hernias.
AB  - PURPOSE: Biologic grafts are rarely used for inguinal herniorrhaphy. The aim of
      this study was to compare the clinical outcomes between patients undergoing a
      Lichtenstein's hernioplasty with a porcine mesh versus a standard synthetic.
      METHODS: A prospective, randomized, double-blinded multicenter, evaluation of
      inguinal hernia repair was conducted between 2008 and 2010. Lichtenstein
      hernioplasty was performed using StratticeTM or lightweight polypropylene
      (Ultrapro) mesh. Quality of life, pain, overall complication rate, and recurrence
      were measured. RESULTS: One hundred and seventy-two patients were randomized to
      StratticeTM (n = 84) or Ultrapro (n = 88). At 3 months postoperatively, there
      were no differences on the occurrence or type of wound events [RR: 0.98 (95% CI
      0.52-1.86, p = 0.69), StratticeTM (15 events) vs. Ultrapro (16 events)]. The mean
      level of impairment caused by the hernia, assessed by Activities Assessment Scale
      (AAS), significantly decreased postoperatively in both groups at 3 months (31%
      StratticeTM and 37% Ultrapro). Patients in the Strattice group reported
      significantly less postoperative pain during postoperative days 1 through 3
      compared to Ultrapro patients. However, the amount of postoperative pain at 3
      months, as assessed by the mean worst pain score on a visual analog scale and the
      Brief Pain Index, was similar between groups (95% CI 1.0-29.3). No hernia
      recurrences were observed in either group. CONCLUSIONS: StratticeTM is safe and
      effective in repairing inguinal hernia, with comparable intra-operative and early
      postoperative morbidity to synthetic mesh. Long-term follow-up is necessary in
      order to know whether the clinical outcomes of Strattice are equivalent to
      standard synthetic mesh in patients undergoing Lichtenstein's hernioplasty.

PMID- 23543335
TI  - Local anaesthetic repair of uncomplicated paraumbilical hernia without sedation:
      peri-operative pain and patient satisfaction.
AB  - PURPOSE: Paraumbilical hernia (PUH) is a common condition that usually requires
      surgical repair. However, there is a dearth of literature on this surgery
      performed under local anaesthesia (LA) without the use of sedation. The aims of
      this study were to assess peri-operative pain and patient satisfaction in
      patients undergoing PUH repair using LA without sedation. METHODS: All patients
      having PUH repair under a single consultant between January 2010 and December
      2011 were eligible to participate. If eligible for both, patients chose either
      general anaesthetic (GA) or LA repair. If only eligible for either LA or GA, they
      were offered this anaesthetic modality. Visual analogue scales were used to
      report peri-operative pain (10 point score) and satisfaction (%). Results were
      compared by grade of surgeon (higher surgical trainee (HST) versus consultant).
      RESULTS: A total of 63 patients underwent PUH repair (31 GA; 32 LA). Of them,
      only 28/32 of LA repair patients agreed to participate. LA and GA patients had
      equivalent age and sex distribution. LA patients had a lower body mass index
      (BMI) than GA [27.1 (3.7) versus 30.3 (5.1), p = 0.007]. The median length of LA
      procedure was 24 (17.5-30) minutes. The median LA solution infiltrated was 25 (20
      32) ml. Peri-operative pain scores were low [1.1 (0.3-2.9) %] and patient
      satisfaction was high [96 (91-99) %]. There were no differences in pain, patient
      satisfaction, duration of procedure and amount of LA infiltrated with increasing
      BMI. Comparing HST to consultant, the former took longer [30 (25-36) versus 20
      (16-24) minutes, p = 0.0007], infiltrated more LA [34.5 (26-47) versus 20 (19
      25.5) ml, p = 0.0039], and patients reported more pain [2.75 (1.0-4.95) versus
      0.4 (0.2-1.7) %, p = 0.029], but overall satisfaction was equivalent [95.5 (89
      99.25) versus 96.3 (92.25-99) %, p = 0.684]. CONCLUSION: Open mesh PUH repair
      using LA without sedation is associated with low peri-operative pain and very
      high satisfaction when either a higher surgical trainee or a consultant grade is
      operating.

PMID- 23543336
TI  - Suture repair of umbilical hernia during caesarean section: a case-control study.
AB  - PURPOSE: The objective of this study was to investigate the additional burdens in
      terms of pain, prolongation of surgery and morbidity which is added to elective
      caesarean section if umbilical hernia suture repair is performed simultaneously.
      Secondly, patient's satisfaction and hernia recurrence rate were assessed.
      METHODS: Consecutive women with symptomatic umbilical hernia undergoing internal
      or external suture repair during elective caesarean were included in this
      retrospective cohort-control study. Data on post-operative pain, duration of
      surgery and morbidity of a combined procedure were collected. These patients were
      matched 1:10 to women undergoing caesarean section only. Additionally, two
      subgroups were assessed separately: external and internal suture hernia repair.
      These subgroups were compared for patient's satisfaction, cosmesis, body image
      and recurrence rate. RESULTS: Fourteen patients with a mean age of 37 years were
      analysed. Internal suture repair (n = 7) prolonged caesarean section by 20 min (p
      = 0.001) and external suture repair (n = 7) by 34 min (p < 0.0001). Suture repair
      did not increase morphine use (0.38 +/- 0.2 vs. 0.4 +/- 02 mg/kg body weight),
      had no procedure-related morbidity and prolonged hospitalization by 0.5 days (p =
      0.01). At a median follow-up of 37 (5-125) months, two recurrences in each
      surgical technique, internal and external suture repair, occurred (28 %). Body
      image and cosmesis score showed a higher level of functioning in internal suture
      repair (p = 0.02; p = 0.04). DISCUSSION: Despite a high recurrence rate, internal
      suture repair of a symptomatic umbilical hernia during elective caesarean section
      should be offered to women if requested. No additional morbidity or scar is added
      to caesarean section. Internal repair is faster, and cosmetic results are better,
      additional skin or fascia dissection is avoided, and it seems to be as effective
      as an external approach. Yet, women must be informed on the high recurrence rate.

PMID- 23543338
TI  - Nitrogen removal with the anaerobic ammonium oxidation process.
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria convert ammonium to N2 with
      nitrite as the terminal electron acceptor in the absence of O2. Nitritation
      anammox bioreactors provide a cost-effective and environment-friendly alternative
      to conventional nitrification/denitrification nitrogen removal systems.
      Currently, this process is only applied for ammonium removal from wastewater with
      high ammonium load and temperature. Nevertheless, recent results obtained with
      laboratory-scale bioreactors suggest new possible routes of application of the
      Nitritation-anammox technology including (1) municipal wastewater treatment,
      removal of (2) methane in combination with nitrite-reducing methane-oxidizing
      bacteria, (3) nitrate coupled to organic acid oxidation and (4) nitrogen oxides.
      The current review summarizes the state-of-the-art of the application of
      Nitritation-anammox systems and discusses the possibilities of utilizing these
      recent results for wastewater treatment.

PMID- 23543337
TI  - Conservative therapeutic approach to corrosive poisonings in adults.
AB  - INTRODUCTION: In this study, we assess the effectiveness of a conservative
      therapeutic treatment of acute corrosive poisonings in adults, and we define
      therapeutic protocols based on clinical and endoscopic criteria. METHODS: We
      analyzed clinical records of patients with acute corrosive poisonings who were
      hospitalized and treated at the Toxicology Clinic at the University of Skopje,
      Republic of Macedonia, during a 5-year period (2006-2010). A total of 481
      patients' records with cases of acute corrosive poisonings were analyzed. There
      were 317 female (65.9 %) and 164 male (34.1 %) patients. The purpose of the
      therapy in the cases of acute corrosive poisonings is to prevent perforation as
      well as progressive fibrosis and stenosis of the esophagus and stomach.
      Therapeutic approach mainly consists of proton pump inhibitors, H(2) blockers,
      antibiotics, and intensive hyperalimentation. There are different opinions
      regarding conservative treatment of acute corrosive poisonings in adults.
      CONCLUSION: Based on our study of corrosive poisonings of adults, we propose a
      list of optimal treatment recommendations.

PMID- 23543339
TI  - Psychotic disorders are more common in ethnic minority than in Dutch native
      defendants.
AB  - PURPOSE: The prevalence of psychotic disorders among prisoners from racial or
      ethnic minority groups remains uncertain. We therefore compared the frequency of
      psychotic disorder in ethnic minority and Dutch native defendants using the
      nationwide database of elaborate pre-trial reports. METHODS: Analysis of a
      nationwide database of pre-trial reported defendants in the Netherlands between
      2000 and 2006 (n = 12,752). RESULTS: A diagnosis of a psychotic disorder was more
      common in ethnic minority than in Dutch native defendants (21.1 vs. 10.2%). The
      odds ratio of this diagnosis, adjusted for age, gender, IQ below 85 and abuse of
      cannabis or hard drugs, was 2.6 (95% CI 2.2-3.0). This odds ratio was highest for
      African defendants (OR = 5.2; 95% CI 3.7-7.4). CONCLUSIONS: Psychotic disorders
      were more common among pre-trial reported defendants from ethnic minorities than
      among their Dutch native counterparts.

PMID- 23543340
TI  - Self-management programmes for people post stroke: a systematic review.
AB  - OBJECTIVE: To examine the evidence base underlying self-management programmes
      specific to stroke survivors. DATA SOURCES: Eleven electronic databases were
      searched using combinations of keywords related to stroke and self-management.
      REVIEW METHODS: Studies involving adults with a clinical diagnosis of stroke,
      which explored self-management interventions, were included. Study selection was
      verified by two reviewers who independently conducted methodological quality
      appraisal and data extraction using a tool developed by The American Academy for
      Cerebral Palsy and Developmental Medicine. RESULTS: Fifteen studies were included
      in this review. Significant treatment effects in favour of the self-management
      intervention were found in six out of nine randomized controlled trials, and
      three out of six non-randomized trials in our review. Four randomized controlled
      trials involving more than 100 participants per trial reported statistically
      significant results in favour of the self-management group in relation to
      measures of disability, confidence in recovery, the stroke specific quality of
      life (sub-scales of family roles and fine motor tasks), and the physical
      component scale of the short form SF-36 Score. The wide range of outcome measures
      used prevented comparison across studies. CONCLUSIONS: This review provides some
      preliminary support for the potential importance of self-management interventions
      after stroke. The most appropriate content and best approach for delivery of
      these interventions remains to be determined. Further high-quality randomized
      controlled trials are needed to test the feasibility, acceptability, and efficacy
      of stroke self-management programmes.

PMID- 23543341
TI  - Group exercise training for balance, functional status, spasticity, fatigue and
      quality of life in multiple sclerosis: a randomized controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of group exercise training on balance,
      functional status, spasticity, fatigue and quality of life in patients with
      multiple sclerosis. DESIGN: A randomized single-blind controlled study. SETTING:
      University hospital, outpatient physical therapy department. SUBJECTS: Ambulatory
      patients with multiple sclerosis. INTERVENTIONS: Exercise group completed a 12
      week group exercise programme under the physical therapists' supervision. Control
      group was included in the waiting list. MAIN MEASURES: The primary outcome
      measures were the Berg Balance Scale, 10-metre walk test, 10-steps climbing test
      and secondary outcome measures were the Modified Ashworth Scale, Fatigue Severity
      Scale and Multiple Sclerosis International Quality of Life. RESULTS: Ninety-nine
      patients completed the study. There were statistically significant improvements
      for all outcome measures in the group exercise group (n = 51) (p < 0.01). In the
      control group (n = 48), there were statistically significant negative change in
      the Berg Balance Scale and 10-metre walk test measures (p = 0.002, p = 0.001) and
      statistically significant increment only in the Fatigue Severity Scale score (p =
      0.002). The Berg Balance Scale score was increased 4.33 in the exercise group,
      while a decreased of 2.33 in control group. The 10-metre walk test duration
      (second) was decreased 2.72 in exercise group, while increased 1.44 in control
      group. In comparing inter-groups changes, both primary and secondary outcome
      mesures showed significant improvements in favour of the exercise group after the
      training (p < 0.05). CONCLUSION: The study demonstrated that supervised group
      exercise training is effective in improving balance, functional status,
      spasticity, fatigue and quality of life in moderately affected people with
      multiple sclerosis, with no worsening of their clinical status.

PMID- 23543342
TI  - A qualitative study exploring patients' experiences of standard care or cardiac
      rehabilitation post minor stroke and transient ischaemic attack.
AB  - OBJECTIVE: To explore individuals' experiences of receiving either standard care
      or comprehensive cardiac rehabilitation post minor stroke or transient ischaemic
      attack. DESIGN: A qualitative study using semi-structured interviews, alongside a
      randomized controlled trial, exploring the effectiveness of comprehensive cardiac
      rehabilitation compared with standard care. Interviews were transcribed verbatim
      and subjected to thematic analysis. SETTING: Individuals' homes. SUBJECTS: People
      who have experienced a minor stroke or transient ischaemic attack and who were
      partaking in a secondary prevention randomized controlled trial (6-7 months post
      the event, 17 males, five females; mean age 67 years). INTERVENTIONS: Not
      relevant. MAIN MEASURES: Not relevant. RESULTS: Four themes were identified:
      information delivery, comparing oneself with others, psychological impact,
      attitudes and actions regarding risk factor reduction. Participants indicated a
      need for improved information delivery, specific to their own risk factors and
      lifestyle changes. Many experienced psychological impact as a result of their
      minor stroke. Participants were found to make two types of social comparison; the
      comparison of self to another affected by stroke, and the comparison of self to
      cardiac patients. CONCLUSION: Comprehensive cardiac rehabilitation was reported
      to have positive effects on people's motivation to exercise. Following a minor
      stroke, many individuals do not recall information given or risk factors specific
      to them. Downward comparison with individuals who have had a cardiovascular event
      led to some underplaying the significance of their minor stroke.

PMID- 23543343
TI  - Patient evaluation of early discharge after hip arthroplasty: development of a
      measure and comparison of three centres with differing durations of stay.
AB  - OBJECTIVE: We compared patients' evaluation of care between a surgical unit with
      a rapid discharge policy and two comparison units to test the hypothesis that the
      centre with rapid discharge has outcomes that are not inferior to those of the
      comparison sites. DESIGN: Cross-sectional cohort study. SUBJECTS: Consecutive
      consenting patients undergoing primary hip arthroplasty during 12 months in: a
      unit that had reduced postoperative stay to median three days; a specialised
      orthopaedic surgery treatment centre with median stay of five days; a traditional
      unit with median stay of six days (N = 316, 125, 119, respectively). METHODS: Six
      weeks postoperatively, patients completed a specially developed questionnaire
      measuring their evaluation of care and recovery, together with measures of
      function and quality of life for validation purposes. RESULTS: Factor analysis of
      questionnaire responses identified two independent components of patients'
      evaluation: problems in staff care and problems in physical recovery. Neither
      component was impaired in the unit with rapid discharge: similar proportions of
      patients reported recovery problems in each site (odds radios (ORs) for the two
      comparators versus unit with rapid discharge: 0.96, 1.18); and more patients
      reported care problems in the two comparator sites (ORs 2.97, 2.16). CONCLUSION:
      Duration of stay after primary hip arthroplasty can be reduced to three days
      without intensive pre- or postoperative care, without detriment to patient
      evaluation.

PMID- 23543344
TI  - Does giving segmental muscle vibration alter the response to botulinum toxin
      injections in the treatment of spasticity in people with multiple sclerosis? A
      single-blind randomized controlled trial.
AB  - OBJECTIVE: To determine if segmental muscle vibration and botulinum toxin-A
      injection, either alone or in combination, reduces spasticity in a sample of
      patients with multiple sclerosis. DESIGN: Single-blind, randomized controlled
      trial. SETTING: Physical medicine and rehabilitation outpatients service.
      SUBJECTS: Forty-two patients affected by the secondary progressive form of
      multiple sclerosis randomized to group A (30 minutes of 120 Hz segmental muscle
      vibration over the rectus femoris and gastrocnemius medial and lateral, three per
      week, over a period of four weeks), group B (botulinum toxin in the rectus
      femoris, gastrocnemius medial and lateral and soleus, and segmental muscle
      vibration) and group C (botulinum toxin). MAIN MEASURES: Modified Ashworth Scale
      at knee and ankle, and Fatigue Severity Scale. All the measurements were
      performed at baseline (T0), 10 weeks (T1) and 22 weeks (T2) postallocation.
      RESULTS: Modified Ashworth Scale at knee and ankle significantly decreased over
      time (p < 0.001) in all groups. Patients in group C displayed a significant
      increase of knee and ankle spasticity at T2 when compared with T1 (p < 0.05).
      Fatigue Severity Scale values in groups A and C were significantly higher at T0
      [A: 53.6 (2.31); C: 48.5 (2.77)] than at either T1 [A: 48.6 (2.21); p = 0.03; C:
      43.5 (3.22); p = 0.03] or T2 [A: 46.7 (2.75); p = 0.02; 42.5 (2.17); p = 0.02],
      while no differences were detected in group B [T0: 43.4 (3.10); T1: 37.3 (3.15);
      T2: 39.7 (2.97)]. CONCLUSION: Segmental muscle vibration and botulinum toxin-A
      reduces spasticity and improves fatigue in the medium-term follow-up in patients
      with multiple sclerosis.

PMID- 23543345
TI  - Very high serum ferritin levels in three newborns with Kawasaki-like illness.
AB  - Kawasaki disease (KD) is an inflammatory condition of unknown etiology that
      affects children, with a peak incidence in the second year of life. KD is
      uncommon in the first year of life and is rare in the newborn period. The present
      report describes three newborn infants who were admitted to hospital with fever
      and nearly identical clinical features of generalized inflammation. The
      presentations did not meet the criteria for KD; however, all three patients
      responded promptly and completely to intravenous immunoglobulin treatment.
      Specifically, the association of these presentations with very high levels of
      serum ferritin is reported. The authors propose that this clinical syndrome
      represents a variant of KD, and that serum ferritin level may be a useful marker
      in diagnosing KD and its variants. Additionally, the association of this clinical
      picture with very high serum ferritin levels raises the possibility of a link
      with hemophagocytic lymphohistiocytosis.

PMID- 23543346
TI  - Comparative effects of flurbiprofen and fentanyl on natural killer cell
      cytotoxicity, lymphocyte subsets and cytokine concentrations in post-surgical
      intensive care unit patients: prospective, randomized study.
AB  - PURPOSE: The purpose of this study was to compare the effect of the long-term
      administration of flurbiprofen and fentanyl in the intensive care unit on natural
      killer cell cytotoxicity (NKCC), lymphocyte subsets and cytokine levels. METHODS:
      In this prospective study, patients scheduled for at least 48 h sedation after
      neck surgery were randomly assigned to two groups called group N and group F.
      Group N patients were sedated with propofol and flurbiprofen after surgery (n =
      12), while group F patients were sedated with propofol and fentanyl (n = 13). The
      NKCC, lymphocyte subsets, and plasma levels of tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, IL-6, and IL-10 were measured before and at the end of
      surgery, on postoperative day (POD) 1 and POD2. RESULTS: The NKCC was
      significantly higher on POD1 in group N than in group F (14.5 +/- 11.2 versus 6.3
      +/- 4.1%, p < 0.05), the difference between the groups disappearing on POD2.
      Lymphocyte subsets and plasma levels of cytokines were not significantly
      different between the two groups during the study period. CONCLUSIONS: Transient
      suppressive effects on NKCC were observed in the fentanyl group as compared to
      the flurbiprofen group. This suggests that when choosing postoperative
      analgesics, physicians should bear in mind the potential immunosuppressive
      effects of these agents in patients requiring prolonged sedation in the intensive
      care unit.

PMID- 23543347
TI  - Is there an association between Ro52/TRIM21 antibodies and rheumatoid factor in
      systemic sclerosis?

PMID- 23543348
TI  - Transcutaneous electrical nerve stimulation (TENS) and exercise: strategy in
      fibromyalgia treatment.

PMID- 23543349
TI  - T cell responses to citrullinated self-peptides in patients with rheumatoid
      arthritis.
AB  - Antibodies to citrullinated peptides(ACPA) have high specificity for diagnosis
      and prognosis in rheumatoid arthritis (RA). ACPA are of IgG isotype and have an
      association with shared epitope-bearing HLA DR allele, suggesting that T cell
      help is needed for their generation. In mice models, T cell reactive to
      citrullinated self-peptide have been reported however, the human data is limited.
      Patients with RA satisfying ACR criteria were included and peripheral blood
      obtained for lymphoproliferative assay, antibody level and HLA typing.
      Citrullinated (Cit) and native peptides of Vimentin and Aggrecan were used for
      stimulating peripheral blood mononuclear cells in 5-day cultures. A SI value
      above >2.0 was taken as significant. HLA typing was done by SSCP and ACPA were
      tested by ELISA. A total of 50 patients (45 females; mean age 42 years; mean
      duration of disease 7 years) with RA were included in the study. A total of 90 %
      were RF positive and 78 % were ACPA positive. A total of 28 patients showed
      response to Agg peptide with 21 of them showing higher response to CitAgg as
      compared to native Agg peptide as well as the median SI was higher with CitAgg
      (6.07 Vs. 5.09; p = 0.009). A total of 31 patients showed response to Vim peptide
      with response to native peptide being higher than CitVim peptide in 22 of the
      patients. There was no association of T cell response with presence of shared
      epitope. Nearly half the patients with RA show T cell response to aggrecan and
      vimentin peptides; however, citrullination is not crucial for T cell response.

PMID- 23543350
TI  - Prize level and debt size: impact on gambling behaviour.
AB  - No studies to date have specifically determined the relationship between prize
      levels, debt size, and impulsivity on reported gambling behaviour on Electronic
      Gaming Machines (EGM). The present study reports the findings of a pilot study
      designed to investigate whether or not the likelihood of increasing the size of a
      bet was related to the level of prize offered and personal debt. The sample
      consisted of 171 first year psychology students (61 males and 120 females).
      Participants completed a series of gambling vignettes designed to elicit data on
      reported bet size according to different prize levels and debt sizes; the Eysenck
      Impulsivity Scale (Eysenck and Eysenck 1977); the Canadian Problem Gambling
      Index; and an author-constructed questionnaire eliciting data on demographic and
      gambling behaviours. Results indicated that as prize levels increase the odds
      (relative risk) of an individual placing a bet on an EGM and the amount of money
      reportedly bet tends to increase. A negative relationship between debt size and
      reported gambling behaviour moderated by prize level was found. No differences
      were found in the odds of placing a bet according to impulsivity. It was
      concluded that prize and debt sizes do influence propensities to gamble and level
      of bets. The findings have implications for restricting jackpot and general prize
      levels as a responsible gambling strategy designed to reduce motivations to
      gamble.

PMID- 23543351
TI  - An allometric model for mapping seed development in plants.
AB  - Despite a tremendous effort to map quantitative trait loci (QTLs) responsible for
      agriculturally and biologically important traits in plants, our understanding of
      how a QTL governs the developmental process of plant seeds remains elusive. In
      this article, we address this issue by describing a model for functional mapping
      of seed development through the incorporation of the relationship between
      vegetative and reproductive growth. The time difference of reproductive from
      vegetative growth is described by Reeve and Huxley's allometric equation. Thus,
      the implementation of this equation into the framework of functional mapping
      allows dynamic QTLs for seed development to be identified more precisely. By
      estimating and testing mathematical parameters that define Reeve and Huxley's
      allometric equations of seed growth, the dynamic pattern of the genetic effects
      of the QTLs identified can be analyzed. We used the model to analyze a soybean
      data, leading to the detection of QTLs that control the growth of seed dry
      weight. Three dynamic QTLs, located in two different linkage groups, were
      detected to affect growth curves of seed dry weight. The QTLs detected may be
      used to improve seed yield with marker-assisted selection by altering the pattern
      of seed development in a hope to achieve a maximum size of seeds at a harvest
      time.

PMID- 23543352
TI  - Next-generation sequencing: a challenge to meet the increasing demand for
      training workshops in Australia.
AB  - The widespread adoption of high-throughput next-generation sequencing (NGS)
      technology among the Australian life science research community is highlighting
      an urgent need to up-skill biologists in tools required for handling and
      analysing their NGS data. There is currently a shortage of cutting-edge
      bioinformatics training courses in Australia as a consequence of a scarcity of
      skilled trainers with time and funding to develop and deliver training courses.
      To address this, a consortium of Australian research organizations, including
      Bioplatforms Australia, the Commonwealth Scientific and Industrial Research
      Organisation and the Australian Bioinformatics Network, have been collaborating
      with EMBL-EBI training team. A group of Australian bioinformaticians attended the
      train-the-trainer workshop to improve training skills in developing and
      delivering bioinformatics workshop curriculum. A 2-day NGS workshop was jointly
      developed to provide hands-on knowledge and understanding of typical NGS data
      analysis workflows. The road show-style workshop was successfully delivered at
      five geographically distant venues in Australia using the newly established
      Australian NeCTAR Research Cloud. We highlight the challenges we had to overcome
      at different stages from design to delivery, including the establishment of an
      Australian bioinformatics training network and the computing infrastructure and
      resource development. A virtual machine image, workshop materials and scripts for
      configuring a machine with workshop contents have all been made available under a
      Creative Commons Attribution 3.0 Unported License. This means participants
      continue to have convenient access to an environment they had become familiar and
      bioinformatics trainers are able to access and reuse these resources. 

PMID- 23543353
TI  - The challenges of delivering bioinformatics training in the analysis of high
      throughput data.
AB  - High-throughput technologies are widely used in the field of functional genomics
      and used in an increasing number of applications. For many 'wet lab' scientists,
      the analysis of the large amount of data generated by such technologies is a
      major bottleneck that can only be overcome through very specialized training in
      advanced data analysis methodologies and the use of dedicated bioinformatics
      software tools. In this article, we wish to discuss the challenges related to
      delivering training in the analysis of high-throughput sequencing data and how we
      addressed these challenges in the hands-on training courses that we have
      developed at the European Bioinformatics Institute. 

PMID- 23543354
TI  - Data construction for phosphorylation site prediction.
AB  - Protein phosphorylation is one of the most pervasive post-translational
      modifications, regulating diverse cellular processes in various organisms. As
      mass spectrometry-based experimental approaches for identifying phosphorylation
      events are resource-intensive, many computational methods have been proposed, in
      which phosphorylation site prediction is formulated as a classification problem.
      They differ in several ways, and one crucial issue is the construction of
      training data and test data for unbiased performance evaluation. In this article,
      we categorize the existing data construction methods and try to answer three
      questions: (i) Is it equivalent to use different data construction methods in the
      assessment of phosphorylation site prediction algorithms? (ii) What kind of test
      data set is unbiased for assessing the prediction performance of a trained
      algorithm in different real world scenarios? (iii) Among the summarized training
      data construction methods, which one(s) has better generalization performance for
      most scenarios? To answer these questions, we conduct comprehensive experimental
      studies for both non-kinase-specific and kinase-specific prediction tasks. The
      experimental results show that: (i) different data construction methods can lead
      to significantly different prediction performance; (ii) there can be different
      test data construction methods that are unbiased with respect to different real
      world scenarios; and (iii) different data construction methods have different
      generalization performance in different real world scenarios. Therefore, when
      developing new algorithms in future research, people should concentrate on what
      kind of scenario their algorithm will work for, what the corresponding unbiased
      test data are and which training data construction method can generate best
      generalization performance.

PMID- 23543355
TI  - Diagnostic value of blood clot core during endobronchial ultrasound-guided
      transbronchial needle aspirate.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is being increasingly used in the sampling of pulmonary masses and
      mediastinal lymphadenopathy. The blood clot core (BCC) often obtained during EBUS
      TBNA may not be a true core and therefore may not be submitted for histological
      analysis. The frequency in which the blood clot core is positive in patients with
      negative cytology undergoing EBUS-TBNA is not known. The purpose of this study
      was to evaluate the diagnostic role of the blood clot core obtained during EBUS
      TBNA. METHODS: An Institutional Review Board-approved retrospective chart review
      was performed from January through September 2011 for all patients who underwent
      EBUS-TBNA at The Ohio State University. The data collection included cytology and
      histology results for each procedure. Blood clot cores obtained from the EBUS
      TBNA needle were sent in formalin for histological examination. RESULTS: Seventy
      patients underwent EBUS-TBNA and 51 (72.8 %) patients had procedures that yielded
      a BCC for histology and aspirate for cytology. Forty-nine percent of patients
      with a BCC were diagnosed with malignancy. Of those with a BCC obtained, five
      (9.8 %) patients diagnosed with malignancy were done so based only on the results
      of blood clot core alone with negative cytology. CONCLUSIONS: Blood clot cores
      obtained at EBUS-TBNA contain diagnostic material and should be subjected
      histopathological examination. When blood clot cores are sent for analysis, there
      is the potential to spare up to 10 % of patients more invasive diagnostic biopsy
      procedures.

PMID- 23543356
TI  - Effects of Jianpi Jiedu Recipe on reversion of P-glycoprotein-mediated multidrug
      resistance through COX-2 pathway in colorectal cancer.
AB  - OBJECTIVE: To evaluate the underlying mechanism of Jianpi Jiedu Recipe (, JJR) in
      the reversion of multidrug resistance concerning colorectal cancer in vitro and
      in vivo. METHODS: Mice were treated orally with JJR at a daily 4.25 g/(kg.day) or
      injected with vinblastine (VCR) 2.5 mg/(kg.day) for 3 weeks after having been
      inoculated with HCT8/V cells; tumor tissues were assayed by hematoxylin and eosin
      staining. Firstly, the effects of JJR on the expression of cyclooxygenase-2 (COX
      2) were tested by real-time polymerase chain reaction (PCR) technique and COX-2
      gene silenced by siRNA. Secondly, the variation of intracellular concentration of
      oxaliplatin (L-OHP) was evaluated by the inductively coupled plasma mass
      spectroscopy (ICPMS) in HCT8/V and its COX-2 siRNA cells; the concentration of
      JJR combined with chemotherapeutic drugs and the reverse effect of multidrug
      resistance (MDR) in HCT8/V cells was evaluated by the MTT assay. Thirdly, real
      time quantitative PCR and Western blot analysis were used to detect the multidrug
      resistance gene 1 (MDR1) mRNA and P-gp expression. RESULTS: JJR had an inhibitory
      effect on the growth of tumors in vivo, and it, in combination with
      chemotherapeutic drugs, could reverse the drug-resistance of HCT8/V cells and
      increase the sensitivity of HCT8/V cells to VCR, DDP, 5-Fu, and THP. ICP-MS
      results showed that JJR could increase the concentration of drugs in HCT8/V cells
      (P<0.01). Furthermore, it was shown that JJR could reverse drug resistance of
      colorectal cancer cells by decreasing MDR1 expression and P-gp level via
      downregulation of COX-2, which has been represented as one of the major
      mechanisms that contributes to the MDR phenotype (P<0.01). CONCLUSION: JJR
      reversed multidrug resistance and enhanced the sensitivity to chemotherapy, which
      could be attributed to the down-regulation of COX-2 in MDR1/P-gp-mediated MDR
      colorectal cancer after chemotherapy.

PMID- 23543357
TI  - Apoptotic effect of cisplatin and cordycepin on OC3 human oral cancer cells.
AB  - OBJECTIVE: To evaluate apoptotic effects of cisplatin and cordycepin as single
      agent or in combination with cytotoxicity in oral cancer cells. METHODS: The
      influences of cisplatin (2.5 MUg/mL) and/or cordycepin treatment (10 or 100
      MUmol/L) to human OC3 oral cancer cell line were investigated by morphological
      observation for cell death appearance, methylthiazoletetrazolium (MTT) assay for
      cell viability, flow cytometry assay for cell apoptosis, and Western blotting for
      apoptotic protein expressions. RESULTS: Data demonstrated that co-administration
      of cisplatin (2.5 MUg/mL) and cordycepin (10 or 100 MUmol/L) resulted in the
      enhancement of OC3 cell apoptosis compared to cisplatin or cordycepin alone
      treatment (24 h), respectively (P <0.05). In flow cytometry assay, percentage of
      cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin (30%)
      was significantly higher than cisplatin (5%) or cordycepin (12%) alone group (P
      <0.05), confirming a synergistically apoptotic effect of cordycepin and
      cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin
      induced more stress-activated protein kinase/Jun terminal kinase (JNK), the
      expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase (PARP)
      as compared to cisplatin or cordycepin alone treatment (P <0.05). CONCLUSION:
      Cisplatin and cordycepin possess synergistically apoptotic effect through the
      activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.

PMID- 23543358
TI  - Targeting the specific vocabulary needs of at-risk preschoolers: a randomized
      study of the effectiveness of an educator-implemented intervention.
AB  - This randomized study examined the effectiveness of a preschool stimulation
      program created to teach words that had been selected by considering the needs of
      the target population of children. Twenty-two educators and their group of at
      risk preschoolers (N = 222, M age = 4.27 years) were assigned to one of two
      conditions: control or intervention. In the latter condition, educators had to
      read specifically developed storybooks to their group and conduct stimulation
      activities. Despite the training and support they received, educators implemented
      the intervention with varying degrees of fidelity. Nonetheless, intent-to-treat
      comparison of the two conditions indicates that children in the intervention
      condition learned the meaning of a much greater number of words than their peers
      in the control condition. In addition, efficacy subset analyses that took into
      account fidelity of implementation show that the greatest gains were made by
      children who had an educator who had implemented the intervention reliably.
      Strategies for scaling up the intervention and optimizing its implementation are
      discussed. 

PMID- 23543359
TI  - Prime time: 18-month violence outcomes of a clinic-linked intervention.
AB  - Prime Time, a youth development intervention, aims to reduce multiple risk
      behaviors among adolescent girls seeking clinic services who are at high risk for
      pregnancy. The purpose of the current study was to examine whether Prime Time
      involvement produced changes in relational aggression, physical violence, and
      related psychosocial and behavioral outcomes. Qualitative case exemplars
      illustrated social contexts of intervention participants with differing
      longitudinal patterns of relational aggression and physical violence. Data were
      from a randomized efficacy trial with 13-17 year-old girls (n = 253) meeting
      specified risk criteria. Intervention participants were involved in Prime Time
      and usual clinic services for 18 months, control participants received usual
      clinic services. Participants in the current study completed self-report surveys
      at baseline and 18 months following enrollment. Outcomes analyses revealed
      significantly lower levels of relational aggression perpetration in the
      intervention group versus controls. In contrast, Prime Time involvement did not
      result in significant reductions in physical violence. Exploratory dose-response
      analyses indicated that reductions in relational aggression may have been most
      pronounced among girls actively involved in Prime Time case management and peer
      leadership activities. Qualitative findings suggested that the intervention's
      emphasis on modeling and building supportive relationships contributed to
      reductions in relational aggression. This study contributes to what has been a
      very limited evidence base regarding effective approaches to preventing violence
      among high-risk adolescent girls. Findings suggest that offering youth
      development interventions through clinic settings hold promise in reducing
      violence risk among vulnerable youth.

PMID- 23543360
TI  - Supporting the transition to adulthood among high school dropouts: an impact
      study of the national guard youth challenge program.
AB  - Using a multi-year, random assignment design, this study evaluated the effects of
      the National Guard Youth Challenge Program (NGYCP), an intensive residential
      intervention program for youth ages 16-18 who have dropped out of high school.
      The sample included 1,173 youth (predominantly male) of diverse racial and ethnic
      backgrounds from ten NGYCP sites across the country. Positive impacts on
      educational and employment outcomes were sustained 3 years after entering the
      program, with older participants generally showing greater benefits than younger
      participants. Implications for research and practice are discussed.

PMID- 23543361
TI  - Gaze alternation in dogs and toddlers in an unsolvable task: evidence of an
      audience effect.
AB  - Dogs have been shown to use human-directed gazing behaviour and gaze alternation
      in numerous contexts; however, it is still unclear whether this behaviour can be
      considered an intentional and referential communicative act. In the current
      study, adult dogs and preverbal toddlers were tested using the classic unsolvable
      task paradigm, but varying the attentional stance of the participating audience
      (the experimenter and the caregiver). The aims were to assess (1) whether dogs
      and toddlers would use gaze alternation behaviour in similar manners when the
      task became unsolvable, and (2) whether both dogs and toddlers would take into
      account the attentional stance of the audience when initiating a communicative
      interaction. Results indicated that both toddlers and dogs increased their gaze
      alternation behaviour between the apparatus and caregiver when the task became
      unsolvable, and toddlers also showed an increase in pointing behaviour.
      Furthermore, both species showed a capacity to take into account the attentional
      stance of the audience when manifesting gaze alternation behaviours towards them.
      Taken together, these results suggest that gaze alternation is both an
      intentional and referential communicative act and that both species can take into
      account the need for audience attention when communicating with them. 

PMID- 23543362
TI  - Inoculation of PAH-degrading strains of Fusarium solani and Arthrobacter oxydans
      in rhizospheric sand and soil microcosms: microbial interactions and PAH
      dissipation.
AB  - Very little is known about the influence of bacterial-fungal ecological
      interactions on polycyclic aromatic hydrocarbon (PAH) dissipation in soils.
      Fusarium solani MM1 and Arthrobacter oxydans MsHM11 can dissipate PAHs in vitro.
      We investigated their interactions and their effect on the dissipation of three
      PAHs-phenanthrene (PHE), pyrene (PYR) and dibenz(a,h)anthracene (DBA)-in planted
      microcosms, in sterile sand or non-sterile soil. In sterile sand microcosms
      planted with alfalfa, the two microbes survived and grew, without any significant
      effect of co-inoculation. Co-inoculation led to the dissipation of 46 % of PHE
      after 21 days. In soil microcosms, whether planted with alfalfa or not, both
      strains persisted throughout the 46 days of the experiment, without any effect of
      co-inoculation or of alfalfa, as assessed by real-time PCR targeting taxon-level
      indicators, i.e. Actinobacteria 16S rDNA and the intergenic transcribed spacer
      specific to the genus Fusarium. The microbial community was analyzed by temporal
      temperature gradient electrophoresis and real-time PCR targeting bacterial and
      fungal rDNA and PAH-ring hydroxylating dioxygenase genes. These communities were
      modified by PAH pollution, which selected PAH-degrading bacteria, by the presence
      of alfalfa and, concerning the bacterial community, by inoculation. PHE and PYR
      concentrations significantly decreased (91 and 46 %, respectively) whatever the
      treatment, but DBA concentration significantly decreased (30 %) in planted and co
      inoculated microcosms only.

PMID- 23543363
TI  - Pusillimonas sp. 5HP degrading 5-hydroxypicolinic acid.
AB  - A bacterial strain 5HP capable of degrading and utilizing 5-hydroxypicolinic acid
      as the sole source of carbon and energy was isolated from soil. In addition, the
      isolate 5HP could also utilize 3-hydroxypyridine and 3-cyanopyridine as well as
      nicotinic, benzoic and p-hydroxybenzoic acids for growth in the basic salt media.
      On the basis of 16S rRNA gene sequence analysis, the isolate 5HP was shown to
      belong to the genus Pusillimonas. Both the bioconversion analysis using resting
      cells and the enzymatic assay showed that the degradation of 5-hydroxypicolinic
      acid, 3-hydroxypyridine and nicotinic acid was inducible and proceeded via
      formation of the same metabolite, 2,5-dihydroxypyridine. The activity of a novel
      enzyme, 5-hydroxypicolinate 2-monooxygenase, was detected in the cell-free
      extracts prepared from 5-hydroxypicolinate-grown cells. The enzyme was partially
      purified and was shown to catalyze the oxidative decarboxylation of 5
      hydroxypicolinate to 2,5-dihydroxypyridine. The activity of 5-hydroxypicolinate 2
      monooxygenase was dependent on O2, NADH and FAD. 

PMID- 23543364
TI  - Bisphosphorylated PEA-15 sensitizes ovarian cancer cells to paclitaxel by
      impairing the microtubule-destabilizing effect of SCLIP.
AB  - Paclitaxel is a standard chemotherapeutic agent for ovarian cancer. PEA-15
      (phosphoprotein enriched in astrocytes-15 kDa) regulates cell proliferation,
      autophagy, apoptosis, and glucose metabolism and also mediates AKT-dependent
      chemoresistance in breast cancer. The functions of PEA-15 are tightly regulated
      by its phosphorylation status at Ser104 and Ser116. However, the effect of PEA-15
      phosphorylation status on chemosensitivity of cancer cells remains unknown. Here,
      we tested the hypothesis that PEA-15 phosphorylated at both Ser104 and Ser116
      (pPEA-15) sensitizes ovarian cancer cells to paclitaxel. We first found that
      knockdown of PEA-15 in PEA-15-high expressing HEY and OVTOKO ovarian cancer cells
      resulted in paclitaxel resistance, whereas re-expression of PEA-15 in these cells
      led to paclitaxel sensitization. We next found that SKOV3.ip1-DD cells
      (expressing phosphomimetic PEA-15) were more sensitive to paclitaxel than
      SKOV3.ip1-AA cells (expressing nonphosphorylatable PEA-15). Compared with
      SKOV3.ip1-vector and SKOV3.ip1-AA cells, SKOV3.ip1-DD cells displayed reduced
      cell viability, inhibited anchorage-independent growth, and augmented apoptosis
      when treated with paclitaxel. Furthermore, HEY and OVTOKO cells displayed
      enhanced paclitaxel sensitivity when transiently overexpressing phosphomimetic
      PEA-15 and reduced paclitaxel sensitivity when transiently overexpressing
      nonphosphorylatable PEA-15. These results indicate that pPEA-15 sensitizes
      ovarian cancer cells to paclitaxel. cDNA microarray analysis suggested that SCLIP
      (SCG10-like protein), a microtubule-destabilizing protein, is involved in pPEA-15
      mediated chemosensitization. We found that reduced expression and possibly
      posttranslational modification of SCLIP following paclitaxel treatment impaired
      the microtubule-destabilizing effect of SCLIP, thereby promoting induction of
      mitotic arrest and apoptosis by paclitaxel. Our findings highlight the importance
      of pPEA-15 as a promising target for improving the efficacy of paclitaxel-based
      therapy in ovarian cancer.

PMID- 23543365
TI  - Gossypin as a novel selective dual inhibitor of V-RAF murine sarcoma viral
      oncogene homolog B1 and cyclin-dependent kinase 4 for melanoma.
AB  - Mutation in the BRAF gene (BRAFV600E) exists in nearly 70% of human melanomas.
      Targeted therapy against BRAFV600E kinase using a recently identified RAF
      selective inhibitor, PLX4032, has been successful in early clinical trials.
      However, in patients with the normal BRAF allele (wild-type), PLX4032 is
      protumorigenic. This conundrum identifies the unmet need for novel therapeutic
      agents to target BRAFV600E kinase that are not counterproductive. We have
      identified gossypin, a pentahydroxy flavone, as a potent antimelanoma agent.
      Gossypin inhibited human melanoma cell proliferation, in vitro, in melanoma cell
      lines that harbor both BRAFV600E kinase and cyclin-dependent kinase 4 (CDK4) as
      well as in cells with BRAF wild-type allele. Gossypin inhibited kinase activities
      of BRAFV600E and CDK4, in vitro, possibly through direct binding of gossypin with
      these kinases, as confirmed by molecular docking studies. For cells harboring the
      BRAFV600E, gossypin inhibited cell proliferation through abrogation of the MEK
      ERK-cyclin D1 pathway and in cells with BRAF wild-type allele, through
      attenuation of the retinoblastoma-cyclin D1 pathway. Furthermore, gossypin
      significantly inhibited melanoma growth in an organotypic three-dimensional skin
      culture mimicking human skin. Gossypin (10 and 100 mg/kg) treatment for 10 days
      in human melanoma (A375) cell xenograft tumors harboring BRAFV600E significantly
      reduced tumor volume through induction of apoptosis and increased survival rate
      in mice, and the effect was significantly superior to that of PLX4032 (10 mg/kg)
      or roscovitine 10 mg/kg. In summary, this study identified gossypin as a novel
      agent with dual inhibitory effects for BRAFV600E kinase and CDK4 for treatment of
      melanoma.

PMID- 23543367
TI  - Plant hormones and their intricate signaling networks: unraveling the nexus.

PMID- 23543366
TI  - Wuschel overexpression promotes somatic embryogenesis and induces organogenesis
      in cotton (Gossypium hirsutum L.) tissues cultured in vitro.
AB  - KEY MESSAGE: This work shows that overexpression of the WUS gene from Arabidopsis
      enhanced the expression of embryogenic competence and triggered organogenesis
      from some cells of the regenerated embryo-like structures. Agrobacterium-mediated
      genetic transformation of cotton was described in the late 1980s, but is still
      time consuming and largely genotype dependant due to poor regeneration. To help
      solve this bottleneck, we over-expressed the WUSCHEL (WUS) gene, a homeobox
      transcription factor cloned in Arabidopsis thaliana, known to stimulate
      organogenesis and/or somatic embryogenesis in Arabidopsis tissues cultured in
      vitro. The AtWUS gene alone, and AtWUS gene fused to the GFP marker were compared
      to the GFP gene alone and to an empty construct used as a control. Somatic
      embryogenesis was improved in WUS expressed calli, as the percentage of explants
      giving rise to embryogenic tissues was significantly higher (*3) when WUS gene
      was over-expressed than in the control. An interesting result was that WUS
      embryogenic lines evolved in green embryo-like structures giving rise to ectopic
      organogenesis never observed in any of our previous transformation experiments.
      Using our standard in vitro culture protocol, the overexpression of AtWUS in
      tissues of a recalcitrant variety did not result in the production of regenerated
      plants. This achievement will still require the optimization of other non-genetic
      factors, such as the balance of exogenous phytohormones. However, our results
      suggest that targeted expression of the WUS gene is a promising strategy to
      improve gene transfer in recalcitrant cotton cultivars.

PMID- 23543368
TI  - Lumbar plexopathy following instrumented posterior lumbar interbody fusion: a
      complication with use of Hohmann's retractor.
AB  - INTRODUCTION: A series of 12 patients in our centre following single level
      instrumented posterior lumbar interbody fusion at L4-L5 developed unexplainable
      motor weakness in the proximal lumbar nerve roots (L2, L3) and numbness of the
      whole limb, a clinical picture resembling lumbar plexopathy. Even though lumbar
      plexopathy has been reported following gynaecological procedures and in
      transpsoas interbody fusion surgeries, there is no literature reporting this
      complication following conventional instrumented posterior lumbar interbody
      fusions. STUDY DESIGN: Retrospective observational study. OBJECTIVE: To find the
      possible mechanism of development of lumbar plexopathy in patients who underwent
      posterior lumbar interbody fusion surgeries in our centre. MATERIAL AND METHODS:
      We analyzed retrospectively the medical records, electrophysiological reports of
      the patients, literatures on the anatomy of lumbar plexus and other literature
      reporting similar complications. We also dissected lumbar plexus of three
      cadavers and simulated surgical technique on them to find the mechanism of
      development of this unusual complication. RESULTS: We found injury to lumbar
      plexus that probably occurred intraoperatively with Hohmann's retractor that was
      used for retraction of the paraspinal muscles. This theory was favoured by many
      clinical factors and further confirmed by cadaveric dissections. CONCLUSION: We
      conclude that surgical technique with improper use of Hohmann's retractor causes
      traction and compression injury to the lumbar plexus resulting in this
      complication. We propose proper technique of insertion of Hohmann's retractor and
      also recommend use of modified Hohmann's retractor with shorter tips for spinal
      procedures to prevent such complication.

PMID- 23543369
TI  - MRI features of the psoas major muscle in patients with low back pain.
AB  - PURPOSE: The purpose was to investigate the changes of the psoas major muscles
      (PM) cross-sectional area (CSA) and fat infiltration in the PM and to investigate
      the association between the morphology of the PM and expression of the
      degenerative changes of lumbar spine in patients with low back pain (LBP).
      METHODS: T2-weighted scans for measurements of the CSA and analysis of fat
      infiltration were performed on 42 patients and 49 controls using a 1.5 Tesla MR
      system. For a quantitative analysis of fat tissue infiltration a 4-grade visual
      scale was used. RESULTS: Patients had bigger CSA of the PM than controls at the
      levels of L3/L4 and L4/L5 intervertebral disc (P < 0.05). Patients with apparent
      degenerative changes of the lumbar spine had smaller CSA of the PM compared to
      the patients without apparent changes at the levels of L3/L4 and L4/L5 (P <
      0.05). At the levels of L4/L5 and L5/S1 patients with present Modic changes in
      the lumbar vertebral bodies showed smaller CSA of the PM compared to the patients
      without Modic changes (P < 0.05). However, CSA of the PM in the patients with
      degenerative changes of lumbar spine and Modic changes was still bigger than the
      one of the controls. At all analyzed levels correlation between CSAs of the PM
      and fat infiltration of the lumbar paraspinal muscles was negative. CONCLUSION:
      Results suggest increased activity of the PM in LBP patients but PM also remains
      active regardless of the presence of degenerative and Modic changes of the lumbar
      spine.

PMID- 23543370
TI  - Reliability of cervical lordosis and global sagittal spinal balance measurements
      in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Radiological reproducibility study. PURPOSE: To assess intra and
      interobserver reliability of radiographic measurements for global sagittal
      balance parameters and sagittal spine curves, including cervical spine. Sagittal
      spine balance in adolescent idiopathic scoliosis (AIS) is a main issue and many
      studies have been reported, showing that coronal and sagittal deformities often
      involve sagittal cervical unbalance. Global sagittal balance aims to obtain a
      horizontal gaze and gravity line at top of hips when subject is in a static
      position, involving adjustment of each spine curvature in the sagittal plane. To
      our knowledge, no study did use a methodologically validated imaging analysis
      tool able to appreciate sagittal spine contours and distances in AIS and
      especially in the cervical region. METHODS: Lateral full-spine low-dose EOS
      radiographs were performed in 75 patients divided in three groups (control
      subjects, AIS, operated AIS). Three observers digitally analyzed twice each
      radiograph and 11 sagittal measures were collected for each image. Reliability
      was assessed calculating intraobserver Pearson's r correlation coefficient,
      interobserver intra-class correlation coefficient (ICC) completed with a two-by
      two Bland-Altman plot analysis. RESULTS: This measurement method has shown
      excellent intra and interobserver reliability in all parameters, sagittal
      curvatures, pelvic parameters and global sagittal balance. CONCLUSIONS: This
      study validated a simple and efficient tool in AIS sagittal contour analysis. It
      defined new relevant landmarks allowing to characterize cervical segmental
      curvatures and cervical involvement in global balance.

PMID- 23543371
TI  - Knowledge and willingness to provide research biospecimens among foreign-born
      Latinos using safety-net clinics.
AB  - Latinos tend to be under-represented in cancer research and in bio-repositories.
      We conducted a Spanish-language, interviewer-administered cross-sectional survey
      of 331 foreign-born Latinos from Central and South America attending safety-net
      clinics in order to describe factors associated with knowledge about and
      intention to provide bio-specimens for research purposes. We used logistic
      regression and multiple imputation methods to evaluate associations between socio
      cultural measures, medical trust, demographics, as well as knowledge about and
      intentions to provide bio-specimens. Almost half (47 %) of respondents knew what
      bio-specimens were, and 67 % said that they would provide a specimen after being
      given information about what this involved; this increased to 72 % among those
      with prior knowledge. Controlling for covariates, Latinos with a high school
      education and above were more likely to know what a bio-specimen was and to say
      they would provide bio-specimens than were those with lower levels of education
      [adjusted OR (aOR) 2.85, 95 % CI 1.37-5.96; and 3.49, 95 % CI 1.41-8.63, p <=
      0.01, respectively]. Those with greater social integration were more likely to
      know about bio-specimens than those with less integration (aOR 2.54, 95 % CI 1.45
      4.46, p = 0.001). Higher endorsement of family values was independently
      associated with intent to give bio-specimens (aOR 1.11, 95 % CI 1.02-1.20, p =
      0.017 per five-point increase in "familism" score). Medical mistrust was not
      related to intentions to provide specimens. Our results suggest that
      interventions to increase willingness to provide bio-specimens could leverage
      trusted clinics or social networks and should consider individuals' education and
      socio-cultural perspectives. 

PMID- 23543372
TI  - Traveling towards disease: transportation barriers to health care access.
AB  - Transportation barriers are often cited as barriers to healthcare access.
      Transportation barriers lead to rescheduled or missed appointments, delayed care,
      and missed or delayed medication use. These consequences may lead to poorer
      management of chronic illness and thus poorer health outcomes. However, the
      significance of these barriers is uncertain based on existing literature due to
      wide variability in both study populations and transportation barrier measures.
      The authors sought to synthesize the literature on the prevalence of
      transportation barriers to health care access. A systematic literature search of
      peer-reviewed studies on transportation barriers to healthcare access was
      performed. Inclusion criteria were as follows: (1) study addressed access
      barriers for ongoing primary care or chronic disease care; (2) study included
      assessment of transportation barriers; and (3) study was completed in the United
      States. In total, 61 studies were reviewed. Overall, the evidence supports that
      transportation barriers are an important barrier to healthcare access,
      particularly for those with lower incomes or the under/uninsured. Additional
      research needs to (1) clarify which aspects of transportation limit health care
      access (2) measure the impact of transportation barriers on clinically meaningful
      outcomes and (3) measure the impact of transportation barrier interventions and
      transportation policy changes. 

PMID- 23543375
TI  - Symptomatic bleeding from an intracerebral cavernoma after intravenous
      thrombolysis for ischemic stroke.

PMID- 23543373
TI  - Assessing patient-reported peripheral neuropathy: the reliability and validity of
      the European Organization for Research and Treatment of Cancer QLQ-CIPN20
      Questionnaire.
AB  - PURPOSE: This clinimetric analysis was conducted to evaluate the reliability,
      validity, and responsiveness to changeover time of the QLQ-CIPN20 when used to
      quantify patient-reported chemotherapy-induced peripheral neuropathy (CIPN).
      METHODS: Participants recruited to four cooperative group trials were pooled to
      create two groups (n = 376, 575): those who did versus did not receive neurotoxic
      chemotherapy. QLQ-CIPN20 internal consistency reliability was assessed using
      Cronbach's alpha coefficients. Instrument validity was assessed using factor
      analysis, by evaluating score correlations with other CIPN and pain measures, and
      by comparing scores between contrasting groups. Cohen's d was used to assess
      responsiveness to change. RESULTS: Alpha coefficients for the sensory, motor, and
      autonomic scales were 0.88, 0.88, and 0.78, respectively. However, autonomic
      scale and hearing loss items exhibited low item-item correlations (r <= 0.30) and
      thus were deleted. Moderate correlations were found between QLQ-CIPN20 and Brief
      Pain Inventory pain severity items (r 0.30-0.57, p <= .0001). Correlation between
      the QLQ-CIPN20 sensory and toxicity grading scale scores was low (r = .20; p <=
      .01). Mean scores were higher (worse) (p <= 0.0001) in individuals who did versus
      did not receive neurotoxic chemotherapy. The sensory and motor scales exhibited
      moderate-high responsiveness to change (Cohen's d = 0.82 and 0.48, respectively).
      Factor analysis indicated that the 16-item version formed distinct factors for
      lower and upper extremity CIPN, delineating typical distal to proximal CIPN
      progression. CONCLUSIONS: Results provide support for QLQ-CIPN20 sensory and
      motor scale reliability and validity. The more parsimonious and clinically
      relevant 16-item version merits further consideration.

PMID- 23543376
TI  - Profile of microRNAs in the plasma of Parkinson's disease patients and healthy
      controls.

PMID- 23543377
TI  - Prothrombotic burden in a patient with recurrent thrombotic events: might an
      early assessment of thrombophilia be useful in the presence of a strong family
      history for vascular events?

PMID- 23543378
TI  - Gray matter atrophy in progressive supranuclear palsy: meta-analysis of voxel
      based morphometry studies.
AB  - Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray
      matter (GM) atrophy in patients with progressive supranuclear palsy (PSP)
      relative to healthy controls (HC). However, not all findings have been entirely
      concordant. Herein, we performed a quantitative meta-analysis study in order to
      consistently quantify GM anomalies in PSP. We conducted a systematic search for
      VBM studies of PSP patients and HC using PubMed and Embase databases from January
      2000 to May 2012. Meta-analysis of these VBM studies was performed using a newly
      improved voxel-based meta-analytic technique, effect-size signed differential
      mapping. A total of 9 cross-sectional VBM studies that involved 143 PSP patients
      and 216 HC subjects met the inclusion criteria. Considerable regional GM volume
      decrease was detected in the thalamus, basal ganglia, midbrain, insular cortex,
      and frontal cortex. These findings remained largely unchanged following jackknife
      sensitivity analyses. The present meta-analysis provided evidence of PSP-specific
      GM atrophy. This finding might help contribute to our understanding of the
      neurobiological basis underlying PSP. 

PMID- 23543379
TI  - Anterior spinal epidural abscess due to Salmonella typhi: a report of a rare case
      treated conservatively and review of the literature.

PMID- 23543380
TI  - Mortality and functional disability after spontaneous intracranial hemorrhage:
      the predictive impact of overall admission factors.
AB  - To determine the effects of different prognostic factors, including previous
      antiplatelet therapy, admission data, and radiographic findings on discharge and
      3-month neurological condition using modified Rankin scale (mRS) and mortality at
      30 days and 3-month follow-up in patients presenting to the emergency department
      with spontaneous intracranial hemorrhage (sICH). Between January and July 2012,
      120 consecutive patients (males 62%, females 38%), who were admitted within 48 h
      of symptoms onset, were included. We recorded the following data on admission:
      demographics; functional scores of ICH, Glasgow Coma Scale, and National
      Institutes of Health Stroke Scale; vital signs; smoking status; use of illicit
      drug; preadmission antiplatelet treatment; results of laboratory tests (platelet
      count, serum glucose, sodium and creatinine levels, and prothrombin time); and
      primary neuroimaging findings [intraventricular hemorrhage (IVH), midline shift,
      and hydrocephalus]. In multivariate analysis using adjusted model for
      demographics and prior antiplatelet therapy; functional scores, laboratory
      results, and diabetes history correlated with mortality during 30 days after the
      event. Moreover, the parameters on the initial computed tomography scan
      significantly increased 30-day fatality rate and was correlated with increase in
      the discharge mRS score of survivors. The odds ratio (OR) and 95% confidence
      interval (CI) of early mortality associated with IVH presentation was 2.34 (CI
      1.76-3.02, p = 0.003). The corresponding ORs in those with midline shift
      displacement and hydrocephalus were 2.18 (95% CI 2.08-3.80, p = 0.01) and 1.62
      (95% CI 1.01-2.63, p = 0.02), respectively. In patients with ICH, prognostic
      factors, include various clinical parameters and paraclinical findings of
      admission time.

PMID- 23543381
TI  - Percutaneous vertebroplasty in a series of myasthenic patients with steroid
      induced symptomatic vertebral fractures.
AB  - Vertebral compression fractures (VFs) are observed in 30-50 % of patients
      affected by steroid-induced osteoporosis, with consequentially severe back pain
      and functional limitation. An alternative treatment to medical therapy for pain
      caused by recent VFs is percutaneous vertebroplasty (PVP). Patients were treated
      by PVP after careful selection, based on the presence of persistent pain not
      resolved by standard medical therapy, correlation between pain and level of the
      VF, and neuroradiological features. We performed PVP in 4 patients with
      generalized MG associated with recent steroid-induced symptomatic VFs. Relief
      from pain was very rapid, usually within 24 h, and retained at a 3-month
      evaluation. No severe complication or MG worsening were observed in the post
      operative period. Although clinical indication for PVP is still controversial, in
      our experience PVP is a useful and safe tool to be considered in the management
      of recent steroid-induced symptomatic VFs in selected MG patients.

PMID- 23543382
TI  - Removal of broken cannulated intramedullary nail after tibiotalocalcaneal
      arthrodesis.

PMID- 23543383
TI  - Ruthenium (II) polypyridyl complexes stabilize the bcl-2 promoter quadruplex and
      induce apoptosis of Hela tumor cells.
AB  - In the present study, the interaction between GC-rich sequence of bcl-2 gene P1
      promoter (Pu39) and two ruthenium (II) polypyridyl complexes, [Ru(bpy)2(tip)]2+
      (1) and [Ru(phen)2(tip)]2+ (2), was investigated by UV-Visible, fluorescence
      spectroscopy, circular dichroism, fluorescence resonance energy transfer melting
      assay and polymerase chain reaction stop assay. Those experimental results
      indicated that the two complexes can effectively stabilize the G-quadruplex of
      Pu39. It was found that the complex 2 exhibited greater cytotoxic activity than 1
      against human Hela cells and can enter into Hela cells in a short period of time
      to effectively induce apoptosis of cells. Further experiments found that
      complexes 1 and 2 had as potent inhibitory effects on ECV-304 cell migration as
      suramin. Those noteworthy results provide new insights into the development of
      anticancer agents for targeting G-quadruplex DNA.

PMID- 23543384
TI  - Risks associated with bacterial vaginosis in infertility patients: a systematic
      review and meta-analysis.
AB  - STUDY QUESTION: Is bacterial vaginosis (BV) associated with the cause of
      infertility and does BV impinge on conception rates and early pregnancy loss
      following IVF? SUMMARY ANSWER: The incidence of BV is significantly higher among
      patients with tubal infertility when compared with patients with non-tubal
      infertility. BV does not impinge on conception rates but is significantly
      associated with preclinical pregnancy loss, though not with first trimester
      abortion. WHAT IS KNOWN ALREADY: BV is prevalent in patients with infertility, as
      evident from studies across the world. STUDY DESIGN, SIZE, DURATION: This study
      is a meta-analysis of data on the prevalence of BV in women with infertility, the
      association between BV and the cause of infertility, and the associations between
      BV and conception rates and early pregnancy loss following IVF. The meta-analyses
      of the various topics involved different numbers of studies: prevalence of BV
      with infertility--12 studies, association with tubal infertility--3 studies and
      associations with conception rates--6 studies, with early preclinical pregnancy
      loss--2 studies and with clinical pregnancy loss--4 studies.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Systematic literature searches of the
      electronic databases, PubMed, EMBASE, CINAHL, the Cochrane Library and ISI Web of
      Knowledge were performed up to September 2012. Studies were included if they
      reported on, at least, one of the following: prevalence of BV in infertility
      patients, association between BV and the cause of infertility, association
      between BV and conception rates with IVF or association between BV and early
      pregnancy loss. Studies were considered eligible if BV was diagnosed through
      standardized criteria like Nugent's criteria or Hay-Ison's criteria. In none of
      the studies, infertility as such was defined, but patients were described as
      unselected patients undergoing IVF. MAIN RESULTS AND THE ROLE OF CHANCE: The
      estimated prevalence of BV (Nugent score >6) in infertile women is 19% [95%
      confidence interval (CI): 14-25%]. Abnormal microflora including BV and
      intermediate microflora (Nugent scores 4-10) occurs in 39% of the infertile
      patients (95% CI: 26-52%). BV is significantly more prevalent in women with
      infertility compared with antenatal women in the same population [OR (odds ratio)
      3.32, 95% CI 1.53-7.20]. BV is significantly more prevalent in women with tubal
      infertility compared with women with other causes of infertility (OR 2.77, 95% CI
      1.62-4.75). BV is not associated with decreased conception rates (OR 1.03, 95% CI
      0.79-1.33). Similarly, none of the studies found an association between abnormal
      vaginal flora and conception rates following IVF treatment. BV is associated with
      a significantly elevated risk of preclinical pregnancy loss (OR 2.36, 95% CI:
      1.24-4.51). BV is not associated with an increased risk of first trimester
      miscarriage (OR 1.20, 95%CI: 0.53-2.75). LIMITATIONS, REASONS FOR CAUTION: All
      included studies were centre based. In addition, publication bias cannot be ruled
      out. Furthermore, all estimates are obtained using an absolute minimum of
      studies. The standard error on the estimates is so large that it does not allow
      for any formal statistical conclusions regarding heterogeneity between the
      effects reported in different studies. WIDER IMPLICATIONS OF THE FINDINGS: It
      needs to be recognized that most inferences drawn in our study rely on a limited
      number of studies, potentially, endangering the generalizability of our findings.
      Moreover, all studies on cause of infertility in relation to BV included had a
      cross-sectional design and, therefore, do not allow for causal inferences. Still,
      there is strong circumstantial evidence that supports a causal link between BV
      and tubal infertility. Studies with a longitudinal design, on the other hand,
      strongly support a relation between BV and early pregnancy loss. Unfortunately,
      no study looked beyond first trimester fetal loss, although it is plausible that
      the high preterm birth rates with IVF are, at least, in part attributable to BV.

PMID- 23543385
TI  - Do endometriomas induce an inflammatory reaction in nearby follicles?
AB  - STUDY QUESTION: Do endometriomas induce an inflammatory reaction with increased
      cytokine concentrations in nearby follicles and thereby affect follicular
      development during controlled ovarian stimulation for in vitro fertilization
      (IVF)? SUMMARY ANSWER: With most endometriomas, there is no evidence of increased
      cytokine concentrations in the ipsilateral leading follicle. Infrequently, the
      concentration of inflammatory cytokines is increased in the follicular fluid (FF)
      and associated with diminished ovarian response. WHAT IS KNOWN ALREADY: The link
      between peritoneal endometriosis, inflammation and infertility is well
      established; however, the association between intraovarian inflammation and
      endometrioma is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort
      study included 117 infertile women undergoing IVF in a tertiary infertility
      clinic at Oslo University Hospital Rikshospitalet, Norway, during the period May
      2009 to September 2011. PARTICIPANTS, SETTING, METHODS: There were 47 patients
      with unilateral endometrioma and 17 patients with bilateral endometrioma, while
      the 53 control patients had unexplained or male factor infertility.
      Concentrations of IL-1beta, IL-6, IL-8, IL-10, IL-12 and TNF-alpha were measured
      in serum and in the fluid of the largest pre-ovulatory follicles from each ovary
      of each participant. MAIN RESULTS AND THE ROLE OF CHANCE: Cytokine levels in the
      follicular fluid from the two ovaries in women with unilateral endometriomas were
      comparable, and were not significantly altered compared with that of control
      groups with male factor infertility, unexplained infertility or bilateral
      endometriomas. Compared with serum levels, the follicular fluid levels of IL-8
      and IL-6 were higher, suggesting a local production or recruitment. The
      follicular fluid IL-8 level varied considerably and showed an inverse
      relationship with IL-12, IL-10 and TNF-?, suggesting a complex interaction
      between various immune cells. A small group of patients (n = 3) had increased
      levels of all follicular fluid cytokines combined with moderately to slightly
      elevated serum levels and these patients had a significantly lower ovarian
      response. LIMITATIONS, REASONS FOR CAUTION: For ethical reasons, the
      endometriomas were diagnosed indirectly by ultrasound rather than by histology.
      WIDER IMPLICATIONS OF THE FINDINGS: This paper reveals that endometriomas seldom
      induce inflammation in nearby follicles during IVF; therefore, routine cystectomy
      prior to IVF may not be necessary. Cytokine levels in the follicular fluid,
      nonetheless, show distinctive patterns and increased levels may be linked to
      reduced ovarian response independent of the cause of infertility.

PMID- 23543386
TI  - An interesting case of a subcutaneous nodule.
AB  - Human dirofilariasis is a zoonotic disease which is caused by the filarial
      nematodes, Dirofilaria repens and Dirofilaria immitis. Dirofilariae are
      transmitted to humans via mosquito bites. Human Dirofilariasis presents commonly
      as subcutaneous nodules, pulmonary nodules or nodules in the eyes. They are
      considered as emerging pathogens. We are presenting a case of human
      Dirofilariasis from Karnataka, which was caused by Dirofilaria repens.

PMID- 23543388
TI  - "Bending the cost curve" in gastroenterology.
AB  - INTRODUCTION: Increasing attention is being focused on reigning in escalating
      costs of healthcare, i.e. trying to 'bend the cost curve'. In gastroenterology
      (GI), inpatient hospital care represents a major component of overall costs. This
      study aimed to characterize the trend in cost of care for GI-related
      hospitalizations in recent years and to identify the most costly diagnostic
      groups. METHODS: All hospital inpatients admitted between January 2008 and
      December 2009 with a primary diagnosis of one of the six most common GI-related
      Diagnosis Related Groups (DRGs) in this hospital system were identified; all DRGs
      contained at least 40 patients during the study period. Patient Level Costing
      (PLC) was used to express the total cost of hospital care for each patient; PLC
      comprised a weighted daily bed cost plus cost of all medical services provided
      (e.g., radiology, pathology tests) calculated according to an activity-based
      costing approach; cost of medications were excluded. All costs were discounted to
      2009 values. Mean length of stay (LOS) was also calculated for each DRG. RESULTS:
      Over 2 years, 470 patients were admitted with one of the six most common GI DRGs.
      Mean cost of care increased from 2008 to 2009 for all six DRGs with the steepest
      increases seen in 'GI hemorrhage (non-complex)' (31 % increase) and
      'Cirrhosis/Alcoholic hepatitis (non-complex)' (45 % increase). No differences in
      readmission rates were observed over time. There was a strong correlation between
      year-to-year change in costs and change in mean LOS, r = 0.93. CONCLUSION: The
      cost of GI-related inpatient care appears to be increasing in recent years with
      the steepest increases observed in non-complex GI hemorrhage and non-complex
      Cirrhosis/Alcoholic hepatitis. Efforts to control the increasing costs should
      focus on these diagnostic categories.

PMID- 23543387
TI  - Micro-regulators of auxin action.
AB  - microRNAs (miRs) are 21- to 24-nucleotide-long RNA molecules that are mainly
      involved in regulating the gene expression at the post-transcriptional levels.
      They are present in a variety of organisms from algae to plants and play an
      important role in gene regulation. The identification of several diverging and
      converging functions of miRs indicates that they play versatile roles in
      regulating plant development including differentiation, organ development, phase
      change, signalling, disease resistance and response to environmental stresses.
      This article provides a concise update on the plant miR functions and their
      targets in the auxin pathway with focus on the interactions between miRs and
      auxin signalling to intricately regulate the plant responses.

PMID- 23543389
TI  - The management gram-negative bacterial haematogenous vertebral osteomyelitis: a
      case series of diagnosis, treatment and therapeutic outcomes.
AB  - PURPOSE: The incidence of gram-negative bacterial haematogenous vertebral
      osteomyelitis (GNB HVO) is increasing. We performed a retrospective cohort study
      of patients with this type of infection in an effort to gain an improved
      understanding of the current clinical presentation, management and outcome.
      METHODS: Between May 2007 and May 2010, all patients, over the age of 18 years,
      suffering from GNB HVO were identified and their microbiological diagnoses were
      evaluated. RESULTS: This study identified seventy-nine patients with
      haematogenous vertebral osteomyelitis (HVO). Of these seventy-nine patients, 10
      patients (12.66%) had Gram-negative organisms isolated. These organisms included
      Escherichia coli (4), Pseudomonas aeruginosa (3), Klebsiella pneumonia (1),
      Haemophilus influenza (1) and Enterobacter cloacae (1). Eight patients were
      successfully treated with antibiotics and/or surgery. Of the eight patients whose
      HVO was cured, five had Ciprofloxacin as part of their definitive antibiotic
      regime. CONCLUSION: The treatment of GNB HVO is often challenging because of
      unpredictable resistance patterns and limited published data on effective
      treatment regimens. Our study has highlighted the need for prompt microbiological
      sampling and initiation of early appropriate antibiotic regime. The most
      effective treatment for GNB HVO was with oral Ciprofloxacin over a period of 6-8
      weeks.

PMID- 23543390
TI  - Clinical characteristics of intraspinal facet cysts following microsurgical
      bilateral decompression via a unilateral approach for treatment of degenerative
      lumbar disease.
AB  - PURPOSE: Primary intraspinal facet cysts in the lumbar spine are uncommon, but it
      is unclear whether cyst incidence increases following decompression surgery and
      if these cysts negatively impact clinical outcome. We examined the prevalence,
      clinical characteristics, and the risk factors associated with intraspinal facet
      cysts after microsurgical bilateral decompression via a unilateral approach
      (MBDU). METHODS: We studied 230 patients treated using MBDU for lumbar
      degenerative disease (133 men and 97 women; mean age 70.3 years). Clinical
      status, as assessed by the Japanese Orthopedic Association (JOA) score and
      findings on X-ray and magnetic resonance images, was evaluated prior to surgery
      and at both 3 months and 1 year after surgery. The prevalence of intraspinal
      facet cysts was determined and preoperative risk factors were defined by
      comparing presurgical findings with clinical outcomes. RESULTS: Thirty-eight
      patients (16.5%) developed intraspinal facet cysts within 1 year postoperatively,
      and 24 exhibited cysts within 3 months. In 10 patients, the cysts resolved
      spontaneously 1 year postoperatively. In total, 28 patients (12.2%) had facet
      cysts 1 year postoperatively. The mean JOA score of patients with cysts 1 year
      postoperatively was significantly lower than that of patients without cysts. This
      poor clinical outcome resulted from low back pain that was not improved by
      conservative treatment. Most cases with spontaneous cyst disappearance were
      symptom-free 1 year later. The preoperative risk factors for postoperative
      intraspinal facet cyst formation were instability (OR 2.47, P = 0.26), scoliotic
      disc wedging (OR 2.23, P = 0.048), and sagittal imbalance (OR 2.22, P = 0.045).
      CONCLUSIONS: Postoperative intraspinal facet cyst formation is a common cause of
      poor clinical outcome in patients treated using MBDU.

PMID- 23543391
TI  - An examination of the PROMIS((r)) pediatric instruments to assess mobility in
      children with cerebral palsy.
AB  - PURPOSE: The Patient-Reported Outcomes Measurement Information System
      (PROMIS((r))) provides adult and pediatric self-report measures of health-related
      quality of life designed for use across medical conditions and the general
      population. The purpose of this study was to examine the feasibility and validity
      of the PROMIS((r)) Pediatric Short Form and computer-adaptive test (CAT) mobility
      measures in children with cerebral palsy (CP). METHODS: Eighty-two children with
      CP completed self-report (PROMIS((r)) Mobility Short Form, PROMIS((r)) Mobility
      CAT, Pediatric Quality of Life InventoryTM) and performance-based assessments of
      mobility (Timed Up and Go, Gross Motor Function Measure). Parents provided three
      proxy reports of child mobility (Pediatric Outcomes Data Collection Instrument,
      Functional Assessment Questionnaire, Shriners Hospitals for Children CP-CAT).
      Validity of PROMIS((r)) instruments was examined through correlations with other
      measures and "known groups" analyses determined by Gross Motor Function
      Classification System (GMFCS). RESULTS: On average, the PROMIS((r)) CAT required
      less than seven items and 2 minutes to administer. Both PROMIS((r)) measures
      showed moderate to high correlations with child- and parent-proxy report of child
      mobility; correlations with performance-based measure were small for the
      PROMIS((r)) Short Form and non-significant for the PROMIS((r)) CAT. All measures
      except for the PROMIS((r)) CAT were able to distinguish between GMFCS categories.
      CONCLUSIONS: Results support the convergent and discriminant validity of the
      pediatric PROMIS((r)) Mobility Short Form in children with CP. The PROMIS((r))
      Mobility CAT correlates well with child report and parent report of mobility but
      not with performance-based measures and does not differentiate between known
      mobility groups.

PMID- 23543392
TI  - Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic
      brain injury.
AB  - This study was undertaken to evaluate the effect of simvastatin, a cholesterol
      lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO)
      levels and neuroprotection, in rats with experimentally induced traumatic brain
      injury (TBI). Forty Wistar albino rats were categorized into four groups: sham
      operated (S), trauma (T), trauma + vehicle (T + V) and trauma + simvastatin (T +
      S). The T, T + V and T + S groups were subjected to TBI. The T + V group was
      administered vehicle [ethanol:saline (1/2)] and the T + S group was administered
      1 mg/kg of simvastatin 3 h after the injury insult. Blood and brain tissue
      specimens were obtained 24 h after the trauma to measure VEGFs and NO levels and
      perform histopathological examinations. The histopathological injury scores of
      brain tissues were significantly higher in the T group, and simvastatin
      significantly prevented brain injury in the T + S group. In the T group,
      significant increases of VEGF levels in serum and brain tissues were noted, which
      were prevented with simvastatin treatment in the T + S group. The markedly high
      levels of NO in brain tissues of the T group were decreased by simvastatin
      treatment in the T + S group. It can be concluded that, as evidenced by
      histopathological findings, simvastatin treatment improves neuropathology in
      acute stages of TBI.

PMID- 23543393
TI  - Cardiovascular autonomic function in lateral medullary infarction.
AB  - Even though the medulla contains the baroreceptor regulatory centers, few studies
      have focused on the autonomic dysfunction of lateral medullary infarction (LMI).
      Therefore, cardiac parasympathetic and sympathetic functions were compared in LMI
      patients and age-matched controls. We prospectively recruited 25 LMI patients who
      had ipsilateral Horner's sign and cardiac autonomic function testing without a
      history of diabetes, cardiac disease, or previous stroke. Parasympathetic
      function tests included beat-to-beat heart rate variation during deep breathing,
      30:15 heart rate ratio testing while standing, and the valsalva ratio.
      Sympathetic function tests included blood pressure during active standing and
      sustained handgrip. The composite autonomic score (CAS) was measured as a total
      of 10 points; parasympathetic dysfunction was designated as >=3 points in the
      parasympathetic subscores and sympathetic dysfunction as >=2 points in the
      sympathetic subscores. Multiple regression analysis was performed to predict
      parasympathetic or sympathetic dysfunction. The mean age and stroke risk factors
      of the study population were not significantly different between the LMI group (n
      = 25) and control group (n = 29). However, cardiac autonomic functions were
      significantly different in the groups: parasympathetic dysfunction (14 vs. 4
      patients, p = 0.011) and sympathetic dysfunction (3 vs. 13 patients, p = 0.008).
      In univariate analysis, male-gender (p = 0.011), right-side involvement (p =
      0.035) and ventral involvement (p = 0.007) were significantly associated with
      parasympathetic dysfunction (CAS subscore >=3). In multivariable analysis, the
      ventral involvement remained to be the independent predictor for parasympathetic
      dysfunction (OR 16.0; 95% CI 2.2-118.3, p = 0.007). This study suggests that LMI
      patients are susceptible to cardiac parasympathetic dysfunction, especially in
      the ventral medulla.

PMID- 23543394
TI  - Non-cognitive symptoms and related conditions in the Alzheimer's disease: a
      literature review.
AB  - The Alzheimer's disease is considered a progressive cognitive disorder; however,
      several non-cognitive symptoms accompany all stages of the disease, appearing at
      times before the cognitive symptoms become manifest. This article reviews the
      literature on non-cognitive symptoms normally related to the Alzheimer's disease,
      including gait and balance dysfunction, olfactory dysfunction, diabetes, pain,
      and psychiatric symptoms. 

PMID- 23543395
TI  - Genome-wide copy number variation in Hanwoo, Black Angus, and Holstein cattle.
AB  - Hanwoo, Korean native cattle, is indigenous to the Korean peninsula. They have
      been used mainly as draft animals for about 5,000 years; however, in the last 30
      years, their main role has been changed to meat production by selective breeding
      which has led to substantial increases in their productivity. Massively parallel
      sequencing technology has recently made possible the systematic identification of
      structural variations in cattle genomes. In particular, copy number variation
      (CNV) has been recognized as an important genetic variation complementary to
      single-nucleotide polymorphisms that can be used to account for variations of
      economically important traits in cattle. Here we report genome-wide copy number
      variation regions (CNVRs) in Hanwoo cattle obtained by comparing the whole genome
      sequence of Hanwoo with Black Angus and Holstein sequence datasets. We identified
      1,173 and 963 putative CNVRs representing 16.7 and 7.8 Mbp from comparisons
      between Black Angus and Hanwoo and between Holstein and Hanwoo, respectively. The
      potential functional roles of the CNVRs were assessed by Gene Ontology enrichment
      analysis. The results showed that response to stimulus, immune system process,
      and cellular component organization were highly enriched in the genic-CNVRs that
      overlapped with annotated cattle genes. Of the 11 CNVRs that were selected for
      validation by quantitative real-time PCR, 9 exhibited the expected copy number
      differences. The results reported in this study show that genome-wide CNVs were
      detected successfully using massively parallel sequencing technology. The CNVs
      may be a valuable resource for further studies to correlate CNVs and economically
      important traits in cattle.

PMID- 23543396
TI  - Enabling interspecies epigenomic comparison with CEpBrowser.
AB  - SUMMARY: We developed the Comparative Epigenome Browser (CEpBrowser) to allow the
      public to perform multi-species epigenomic analysis. The web-based CEpBrowser
      integrates, manages and visualizes sequencing-based epigenomic datasets. Five key
      features were developed to maximize the efficiency of interspecies epigenomic
      comparisons. AVAILABILITY: CEpBrowser is a web application implemented with PHP,
      MySQL, C and Apache. URL: http://www.cepbrowser.org/.

PMID- 23543397
TI  - Anaplastic astrocytoma.
AB  - OPINION STATEMENT: Standard treatment of anaplastic astrocytoma (AA) in good
      performance patients consists of maximal safe surgical resection followed by
      focal, fractionated, external beam radiotherapy (RT) alone or in combination with
      concurrent and adjuvant temozolomide (TMZ). Since prospective data regarding the
      use of chemoradiotherapy for AA is lacking, the practice is based on the
      extrapolation of results from a randomized study in glioblastoma (GB). Whether
      the data from the GB study can and should be extrapolated is controversial,
      although a large multicenter, randomized, phase III study is underway to define
      optimal initial AA treatment. Patients should be tapered off corticosteroids
      completely or to the lowest dose necessary to treat neurologic dysfunction. Anti
      epileptic drugs (AED) are not indicated unless there is a history of seizure;
      levetiracetam is the preferred AED in malignant glioma (MG). Unless there is
      evidence of intracranial hemorrhage, venous thromboembolism (VTE) should be
      treated with low-molecular-weight heparin (LMWH) therapy. At recurrence, patients
      with good performance status are usually treated with cytotoxic chemotherapy
      following, or in lieu of, repeat surgery. TMZ is the preferred chemotherapeutic
      agent in patients without prior exposure; lomustine is recommended for tumors
      resistant to TMZ. In patients with neurologic dysfunction secondary to tumor
      edema and mass effect who are not amenable to surgery, the use of bevacizumab is
      associated with improved neurologic function and better quality of life. Given
      the limited treatment options at tumor recurrence, consideration for enrollment
      on a clinical trial is encouraged.

PMID- 23543399
TI  - Visual assessment of Ki67 at a glance is an easy method to exclude many luminal
      type breast cancers from counting 1000 cells.
AB  - BACKGROUND: The Ki67 labeling index (LI) reflects the proliferative activity of
      breast cancers and defines luminal A and B tumors; however, no detailed method to
      measure Ki67 has been standardized. Here, we propose a fast and easy way to
      evaluate Ki67. METHODS: Immunohistochemical staining of estrogen receptor (ER),
      progesterone receptor (PgR), HER2 and Ki67 (MIB-1) was performed on 235 primary
      invasive ductal carcinomas. For each sample, a hot spot with many Ki67+ cells was
      identified using a low-power field (40*, 4* objective). Three independent areas
      in high-power field (400*) were selected at the hot spot, and all cancer cells in
      the 3 areas were manually counted to calculate LI (% Ki67+ cells). Alternatively,
      micrographs taken at 100* and 200* fields including the hot spot were shown to 2
      pathologists, who visually assessed percentages of Ki67+ cells in 10 % intervals
      at a glance (Eye-10). RESULTS: Eye-10 and LI were strongly correlated (r =
      0.9412, P < 0.0001). All cases of Eye-10 >= 30 % had LI > 14 %; most of those <10
      % had LI < 14 %. Of 170 ER+/HER2- tumors, Eye-10-based subtypes matched 87 % of
      LI-driven subtypes, and interobserver agreement was good (kappa = 0.705).
      CONCLUSION: Eye-10 is far easier than counting many cancer cells and useful for
      classifying breast cancers. Eye-10 can exclude obviously high and low Ki67 cases,
      leaving a "gray zone" around a cutoff point. Combining Eye-10 and manual counting
      is a good candidate for a standard method to evaluate Ki67.

PMID- 23543398
TI  - Relationship between postoperative clopidogrel use and subsequent angiographic
      and clinical outcomes following coronary artery bypass grafting.
AB  - Dual antiplatelet therapy with both aspirin and clopidogrel is increasingly used
      after coronary artery bypass grafting (CABG); however, little is known about the
      safety or efficacy. We sought to determine the relationship between postoperative
      clopidogrel and clinical and angiographic outcomes following CABG. We evaluated
      3,014 patients from PREVENT IV who underwent CABG at 107 US sites. Postoperative
      antiplatelet therapy was left to physician discretion. Risk-adjusted angiographic
      and clinical outcomes were compared in patients taking and not taking clopidogrel
      30 days post-CABG. At 30 days, 633 (21%) patients were taking clopidogrel.
      Clopidogrel users were more likely to have peripheral vascular (15 vs. 11%) and
      cerebrovascular disease (17 vs. 11%), prior myocardial infarction (MI) (46 vs.
      41%), and off-pump surgery (33 vs. 18%). Clopidogrel use was associated with
      statistically insignificant higher graft failure (adjusted odds ratio 1.3; 95%
      confidence interval [CI] [1.0, 1.7]; P = 0.05). At 5-year follow-up, clopidogrel
      use was associated with similar composite rates of death, MI, or
      revascularization (27 vs. 24%; adjusted hazard ratio 1.1; 95% CI [0.9, 1.4]; P =
      0.38) compared with those not using clopidogrel. There was an interaction between
      use of cardiopulmonary bypass and clopidogrel with a trend toward lower 5-year
      clinical events with clopidogrel in patients undergoing off-pump CABG. In this
      observational analysis, clopidogrel use was not associated with better 5-year
      outcomes following CABG. There may be better outcomes with clopidogrel among
      patients having off-pump surgery. Adequately powered randomized clinical trials
      are needed to determine the role of dual antiplatelet therapy after CABG.

PMID- 23543400
TI  - Radiation recall dermatitis induced by trastuzumab.
AB  - We report a case of radiation recall dermatitis caused by trastuzumab. A 55-year
      old woman with metastatic breast cancer received palliative first-line
      trastuzumab/paclitaxel and a salvage partial mastectomy with lymph node
      dissection was subsequently performed. In spite of the palliative setting, the
      pathology report indicated that no residual carcinoma was present, and then she
      underwent locoregional radiotherapy to ensure a definitive response. After
      radiotherapy, she has maintained trastuzumab monotherapy. Nine days after the
      fifth cycle of trastuzumab monotherapy, dermatitis in previously irradiated skin
      developed, with fever. Radiation recall dermatitis triggered by trastuzumab is
      extremely rare. A high fever developed abruptly with a skin rash. This may be the
      first case of this sort to be reported. 

PMID- 23543401
TI  - Acute Effects of MPH on the Parent-Teen Interactions of Adolescents With ADHD.
AB  - This study explored the nature of interactions between adolescent males with ADHD
      and their mothers, and the effects of methylphenidate (MPH) on an analogue parent
      teen interaction task. Twenty-five adolescent males with ADHD ( M = 13.6 years)
      and their mothers and 14 non-ADHD adolescent males ( M = 13.4 years) and their
      mothers completed ratings of perceived dyadic conflict. Behavioral observations
      of dyads during 10-min conflict-resolution tasks were also collected. The ADHD
      dyads completed these tasks twice, with adolescents receiving either 0.3 mg/kg
      MPH or placebo. Videotaped sessions were coded using the Parent-Adolescent
      Interaction Rating Scale. Following the conflict-resolution task, participants
      rated their perceived conflict and affect during the interaction. Findings
      indicated higher conflict in the ADHD dyads, and minimal MPH effects on parent
      teen interactions during the analogue task. Results suggest that stimulant
      medication does not produce meaningful acute effects on parent-teen interactions.

PMID- 23543402
TI  - Validity of the ADHD Bifactor Model in General Community Samples of Adolescents
      and Adults, and a Clinic-Referred Sample of Children and Adolescents.
AB  - OBJECTIVE: This study examined the bifactor models of ADHD in three groups:
      adolescents from the general community ( n = 214), adults from the general
      community ( n = 366), and a clinic sample ( n = 245). METHOD: For the adolescent
      sample, mothers provided ratings of the ADHD symptoms, and their teachers
      provided ratings for Emotional Symptoms, Conduct Problems, Hyperactivity, Peer
      Problems, and Prosocial Behavior. For the adult sample, all adults completed self
      ratings of the ADHD symptoms and measures for depression, anxiety, and stress.
      For the clinic-referred sample, mothers provided ratings of the ADHD symptoms,
      and they were diagnosed for ADHD, Conduct Disorder/Oppositional Defiant Disorder,
      anxiety disorders, and depression disorders. RESULTS: The findings for all
      samples supported the bifactor model, and there were differences in the way the
      general and specific factors correlated with the external variables. CONCLUSION:
      The findings support the validity of the bifactor model.

PMID- 23543403
TI  - Clinical and functional outcomes of the PCCP study: a multi-center prospective
      study in Italy.
AB  - The standard surgical management of hip fractures is associated with tissue
      trauma and bleeding which are added to the fracture injury. The percutaneous
      compression plate (PCCP) is a minimally invasive device that has been
      demonstrated in previous studies to reduce postoperative complications and blood
      loss. This prospective, multi-center, observational study assessed clinical and
      functional outcomes with PCCP as treatment for trochanteric fractures. Patients
      with a stable or unstable proximal femoral fracture of type AO 31.A1 or 31.A2
      were enrolled in eight hospitals in Italy. The primary outcome of interest was
      the recovery of the pre-fracture functional status at 1-year follow-up; secondary
      outcomes of interest included blood transfusions, surgical time, complications,
      and mortality. A total of 273 patients were enrolled. The ASA score was 3 or 4 in
      72.5 % of patients. The mean surgical time was 44.1 min; the mean post-surgery
      blood transfusions was 0.9 units. At 1 year, 48 patients (17.6 %) died, 28 (10.2
      %) were lost to follow-up, 4 patients (1.5 %) were excluded, hence 193 patients
      (70.3 %) were available for final evaluation. At the 1-year follow-up visit, 51.9
      % of patients recovered or improved their pre-fracture modified Harris Hip Score,
      49.1 % of patients improved or maintained their walking abilities, and 66.6 % of
      patients residing at home pre-surgery maintained their domicile. The overall
      mortality rate was 17.6 %. Major complications included two fracture collapses,
      one excessive sliding of the cephalic screw leading to a partial fracture
      collapse and one back-out of the diaphyseal screw. This study demonstrates that
      treatment of trochanteric fractures with PCCP gives good outcomes and significant
      advantages such as low blood loss, short surgical time, low risk of
      complications, and good functional recovery in the majority of the patients.

PMID- 23543404
TI  - Managing major vessel injuries with a Fogarty catheter during chest re-opening in
      children.
AB  - Injury of structures, leading to a major bleeding during chest opening, is a
      severe and potentially life-threatening complication, especially in redo cardiac
      surgery, both in adults and children. In three paediatric redo operations
      performed via midline sternotomy, we managed this complication successfully and
      uneventfully by using an inflated Fogarty catheter to plug the blood leak from
      the injured vessel before repairing the lesion under direct vision in a bloodless
      surgical field. Herein we report in detail the technique used and a comment on
      our experience.

PMID- 23543405
TI  - Oxygenated shunting from right to left: a feasibility study of minimized atrio
      atrial extracorporeal membrane oxygenation for mid-term lung assistance in an
      acute ovine model.
AB  - OBJECTIVES: Right ventricular failure is often the final phase in acute and
      chronic respiratory failure. We combined right ventricular unloading with
      extracorporeal oxygenation in a new atrio-atrial extracorporeal membrane
      oxygenation (ECMO). METHODS: Eleven sheep (65 kg) were cannulated by a 28-Fr
      inflow cannula to the right atrium and a 25-Fr outflow cannula through the
      lateral left atrial wall. Both were connected by a serial combination of a
      microaxial pump (Impella Elect((r)), Abiomed Europe, Aachen, Germany) and a
      membrane oxygenator (Novalung((r))-iLA membrane oxygenator; Novalung GmbH,
      Hechingen, Germany). In four animals, three subsequent states were evaluated:
      normal circulation, apneic hypoxia and increased right atrial after load by
      pulmonary banding. We focused on haemodynamic stability and gas exchange.
      RESULTS: All animals reached the end of the study protocol. In the apnoea phase,
      the decrease in PaO2 (21.4 +/- 3.6 mmHg) immediately recovered (179.1 +/- 134.8
      mmHg) on-device in continuous apnoea. Right heart failure by excessive after load
      decreased mean arterial pressure (59 +/- 29 mmHg) and increased central venous
      pressure and systolic right ventricular pressure; PaO2 and SvO2 decreased
      significantly. On assist, mean arterial pressure (103 +/- 29 mmHg), central
      venous pressure and right ventricular pressure normalized. The SvO2 increased to
      89 +/- 3% and PaO2 stabilized (129 +/- 21 mmHg). CONCLUSIONS: We demonstrated the
      efficacy of a miniaturized atrio-atrial ECMO. Right ventricular unloading was
      achieved, and gas exchange was well taken over by the Novalung. This allows an
      effective short- to mid-term treatment of cardiopulmonary failure, successfully
      combining right ventricular and respiratory bridging. The parallel bypass of the
      right ventricle and lung circulation permits full unloading of both systems as
      well as gradual weaning. Further pathologies (e.g. ischaemic right heart failure
      and acute lung injury) will have to be evaluated.

PMID- 23543407
TI  - RETRACTED ARTICLE: Improving case-based ethics training: how modeling behaviors
      and forecasting influence effectiveness.

PMID- 23543406
TI  - Targeting specific HATs for neurodegenerative disease treatment: translating
      basic biology to therapeutic possibilities.
AB  - Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism
      by which neurons adapt their transcriptional responses to specific developmental
      and environmental cues. While defects within the neural epigenome have
      traditionally been studied in the context of early developmental and heritable
      cognitive disorders, recent studies point to aberrant histone acetylation status
      as a key mechanism underlying acquired inappropriate alterations of genome
      structure and function in post-mitotic neurons during the aging process. Indeed,
      it is becoming increasingly evident that chromatin acetylation status can be
      impaired during the lifetime of neurons through mechanisms related to loss of
      function of histone acetyltransferase (HAT) activity. Several HATs have been
      shown to participate in vital neuronal functions such as regulation of neuronal
      plasticity and memory formation. As such, dysregulation of such HATs has been
      implicated in the pathogenesis associated with age-associated neurodegenerative
      diseases and cognitive decline. In order to counteract the loss of HAT function
      in neurodegenerative diseases, the current therapeutic strategies involve the use
      of small molecules called histone deacetylase (HDAC) inhibitors that antagonize
      HDAC activity and thus enhance acetylation levels. Although this strategy has
      displayed promising therapeutic effects, currently used HDAC inhibitors lack
      target specificity, raising concerns about their applicability. With rapidly
      evolving literature on HATs and their respective functions in mediating neuronal
      survival and higher order brain function such as learning and memory, modulating
      the function of specific HATs holds new promises as a therapeutic tool in
      neurodegenerative diseases. In this review, we focus on the recent progress in
      research regarding epigenetic histone acetylation mechanisms underlying neuronal
      activity and cognitive function. We discuss the current understanding of specific
      HDACs and HATs in neurodegenerative diseases and the future promising prospects
      of using specific HAT based therapeutic approaches.

PMID- 23543408
TI  - The promoter of Bmlp3 gene can direct fat body-specific expression in the
      transgenic silkworm, Bombyx mori.
AB  - The fat body plays multiple, crucial roles in the life of silkworms. Targeted
      expression of transgenes in the fat body of the silkworm, Bombyx mori, is
      important not only for clarifying the function of endogenous genes expressed in
      this tissue, but also for producing valuable recombinant proteins. However, fat
      body-specific gene expression remains difficult due to a lack of suitable tissue
      specific promoters. Here we report the isolation of the fat body-specific
      promoter of Bmlp3, a member of the 30K protein family of silkworms. The 1.1 kb
      fragment from -374 to +738 of Bmlp3 displayed strong promoter activity in the
      cell lines BmE and Spli-221. In transgenic silkworms, a DsRed reporter gene
      controlled by the 1.1 kb Bmlp3 promoter fragment was expressed specifically in
      the fat body in a stage-specific pattern that was nearly identical to the
      endogenous Bmlp3 gene. We conclude that the 1.1 kb Bmlp3 promoter fragment is
      sufficient to direct tissue- and stage-specific expression of transgenes in the
      fat body of silkworms, highlighting the potential use of this promoter for both
      functional genomics research and biotechnology applications. 

PMID- 23543409
TI  - Generation of c-Myc transgenic pigs for autosomal dominant polycystic kidney
      disease.
AB  - After several decades of research, autosomal dominant polycystic kidney disease
      (ADPKD) is still incurable and imposes enormous physical, psychological, and
      economic burdens on patients and their families. Murine models of ADPKD represent
      invaluable tools for studying this disease. These murine forms of ADPKD can arise
      spontaneously, or they can be induced via chemical or genetic manipulations.
      Although these models have improved our understanding of the etiology and
      pathogenesis of ADPKD, they have not led to effective treatment strategies. The
      mini-pig represents an effective biomedical model for studying human diseases, as
      the pig's human-like physiological processes help to understand disease
      mechanisms and to develop novel therapies. Here, we tried to generate a
      transgenic model of ADPKD in pigs by overexpressing c-Myc in kidney tissue.
      Western-blot analysis showed that c-Myc was overexpressed in the kidney, brain,
      heart, and liver of transgenic pigs. Immunohistochemical staining of kidney
      tissue showed that exogenous c-Myc predominantly localized to renal tubules.
      Slightly elevated blood urea nitrogen levels were observed in transgenic pigs 1
      month after birth, but no obvious abnormalities were detected after that time. In
      the future, we plan to subject this model to renal injury in an effort to promote
      ADPKD progression.

PMID- 23543410
TI  - Muscle-specific transgenic expression of porcine myostatin propeptide enhances
      muscle growth in mice.
AB  - Myostatin is a well-known negative regulator of skeletal muscle growth.
      Inhibition of myostatin activity results in increased muscle mass. Myostatin
      propeptide, as a myostatin antagonist, could be applied to promote meat
      production in livestock such as pigs. In this study, we generated a transgenic
      mouse model expressing porcine myostatin propeptide under the control of muscle
      specific regulatory elements. The mean body weight of transgenic mice from a line
      expressing the highest level of porcine myostatin propeptide was increased by 5.4
      % (P = 0.023) and 3.2 % (P = 0.031) in males and females, respectively, at 8
      weeks of age. Weight of carcass, fore limb and hind limb was respectively
      increased by 6.0 % (P = 0.038), 9.0 % (P = 0.014), 8.7 % (P = 0.036) in
      transgenic male mice, compared to wild-type male controls at the age of 9 weeks.
      Similarly, carcass, fore limb and hind limb of transgenic female mice was 11.4 %
      (P = 0.002), 14.5 % (P = 0.006) and 14.5 % (P = 0.03) respectively heavier than
      that of wild-type female mice. The mean cross-section area of muscle fiber was
      increased by 17 % (P = 0.002) in transgenic mice, in comparison with wild-type
      controls. These results demonstrated that porcine myostatin propeptide is
      effective in enhancement of muscle growth. The present study provided useful
      information for future study on generation of transgenic pigs overexpressing
      porcine myostatin propeptide for improvement of muscle mass. 

PMID- 23543411
TI  - Enlarged parietal foramina: a rare finding in a female Greek skull with unusual
      multiple Wormian bones and a rich parietal vascular network.
AB  - Enlarged parietal foramina (>5 mm) is an extremely rare developmental defect of
      the parietal bone, which is distinguished from the normal small parietal
      foramina, as genes associated with this entity have been identified, suggesting
      that it is hereditary in nature. We describe a dry skull of a 35-year-old female,
      with enlarged parietal foramina symmetrically situated bilaterally, oval in
      shape, measuring 4.5 * 9.3 mm (right) and 4.9 * 9.2 mm (left) in size. The
      foramina coexisted with multiple Wormian bones in several sites of the skull. On
      the inner parietal bone surface, the anterior, posterior and lateral foramina's
      rims carried grooves, which were continuous with the middle meningeal vessels'
      branches, indicating that a rich vascular network existed around the foramina.
      These vascular grooves also notched the external table at the margin of the
      foramina, which suggests a potential communication between the meningeal and the
      scalp vessels. In addition, this vascular variation should be taken into
      consideration when performing surgical interventions in the area, because the
      large vascular supply to the foramina is a possible source of extensive bleeding.
      Moreover, the interaction of intracranial and extracranial veins and the fact
      that the blood flows in them in both directions, as they are valveless, could
      represent a possible pathway for infections to spread in the cranial cavity.

PMID- 23543412
TI  - Nicotine-induced structural plasticity in mesencephalic dopaminergic neurons is
      mediated by dopamine D3 receptors and Akt-mTORC1 signaling.
AB  - Although long-term exposure to nicotine is highly addictive, one beneficial
      consequence of chronic tobacco use is a reduced risk for Parkinson's disease. Of
      interest, these effects both reflect structural and functional plasticity of
      brain circuits controlling reward and motor behavior and, specifically,
      recruitment of nicotinic acetylcholine receptors (nAChR) in mesencephalic
      dopaminergic neurons. Because the underlying cellular mechanisms are poorly
      understood, we addressed this issue with use of primary cultures of mouse
      mesencephalic dopaminergic neurons. Exposure to nicotine (1-10 MUM) for 72 hours
      in vitro increased dendritic arborization and soma size in primary cultures.
      These effects were blocked by mecamylamine and dihydro-beta-erythroidine, but not
      methyllycaconitine. The involvement of alpha4beta2 nAChR was supported by the
      lack of nicotine-induced structural remodeling in neurons from alpha4 null mutant
      mice (KO). Challenge with nicotine triggered phosphorylation of the extracellular
      signal-regulated kinase (ERK) and the thymoma viral proto-oncogene (Akt),
      followed by activation of the mammalian target of rapamycin complex 1 (mTORC1)
      dependent p70 ribosomal S6 protein kinase. Upstream pathway blockade using the
      phosphatidylinositol 3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1
      benzopyran-4-one hydrochloride] resulted in suppression of nicotine-induced
      phosphorylations and structural plasticity. These effects were dependent on
      functional DA D3 receptor (D3R), because nicotine was inactive both in cultures
      from D3R KO mice and after pharmacologic blockade with D3R antagonist trans-N-4-2
      (6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethylcyclohexyl-4
      quinolinecarboxamide (SB-277011-A) (50 nM). Finally, exposure to nicotine in
      utero (5 mg/kg/day for 5 days) resulted in increased soma area of DAergic neurons
      of newborn mice, effects not observed in D3 receptor null mutant mice mice. These
      findings indicate that nicotine-induced structural plasticity at mesencephalic
      dopaminergic neurons involves alpha4beta2 nAChRs together with dopamine D3R
      mediated recruitment of ERK/Akt-mTORC1 signaling.

PMID- 23543414
TI  - Fast simulation of reconstructed phylogenies under global time-dependent birth
      death processes.
AB  - MOTIVATION: Diversification rates and patterns may be inferred from reconstructed
      phylogenies. Both the time-dependent and the diversity-dependent birth-death
      process can produce the same observed patterns of diversity over time. To develop
      and test new models describing the macro-evolutionary process of diversification,
      generic and fast algorithms to simulate under these models are necessary.
      Simulations are not only important for testing and developing models but play an
      influential role in the assessment of model fit. RESULTS: In the present article,
      I consider as the model a global time-dependent birth-death process where each
      species has the same rates but rates may vary over time. For this model, I derive
      the likelihood of the speciation times from a reconstructed phylogenetic tree and
      show that each speciation event is independent and identically distributed. This
      fact can be used to simulate efficiently reconstructed phylogenetic trees when
      conditioning on the number of species, the time of the process or both. I show
      the usability of the simulation by approximating the posterior predictive
      distribution of a birth-death process with decreasing diversification rates
      applied on a published bird phylogeny (family Cettiidae). AVAILABILITY: The
      methods described in this manuscript are implemented in the R package TESS,
      available from the repository CRAN (http://cran.r
      project.org/web/packages/TESS/). SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 23543413
TI  - A re-evaluation of the role of hCTR1, the human high-affinity copper transporter,
      in platinum-drug entry into human cells.
AB  - Cisplatin (cDDP) is an anticancer drug used in a number of malignancies,
      including testicular, ovarian, cervical, bladder, lung, head, and neck cancers.
      Its use is limited by the development of resistance, often rationalized via
      effects on cellular uptake. It has been claimed that human copper transporter 1
      (hCTR1), the human high-affinity copper transporter, is the major entry pathway
      for cDDP and related drugs via a mechanism that mimics copper. This is an
      unexpected property of hCTR1, a highly selective copper (I) transporter. We
      compared the uptake rates of copper with cDDP (and several analogs) into human
      embryonic kidney 293 cells overexpressing wild-type or mutant hCTR1, mouse
      embryonic fibroblasts that do or do not express CTR1, and human ovarian tumor
      cells that are sensitive or resistant to cDDP. We have also compared the effects
      of extracellular copper, which causes regulatory endocytosis of hCTR1, to those
      of cDDP. We confirm the correlation between higher hCTR1 levels and higher
      platinum drug uptake in tumor cells sensitive to the drug. However, we show that
      hCTR1 is not the major entry route of platinum drugs, and that the copper
      transporter is not internalized in response to extracellular drug. Our data
      suggest the major entry pathway for platinum drugs is not saturable at relevant
      concentrations and not protein-mediated. Clinical trials have been initiated that
      depend upon regulating membrane levels of hCTR1. If reduced drug uptake is a
      major factor in resistance, hCTR1 is unlikely to be a productive target in
      attempts to enhance efficacy, although the proteins involved in copper
      homeostasis may play a role.

PMID- 23543415
TI  - Patient-reported quality-of-life after radiofrequency ablation of varicose veins
      compared to conventional surgery.
AB  - AIM: The aim of this study was to compare patient-reported quality-of-life scores
      after radiofrequency ablation (RFA) compared to conventional surgery using the
      Aberdeen Varicose Vein Questionnaire (AVVQ). METHODS: A postal questionnaire
      based on the AVVQ was sent out to 105 patients who underwent RFA and 50 patients
      who underwent surgery for varicose veins in our unit over a 14-month period.
      Responses were analysed according to sex and compared between the two groups to
      determine if there is a difference in the patient-reported quality-of-life
      scores. The mean AVVQ was calculated for both groups. RESULTS: Responses were
      received from 57 patients who underwent RFA and 27 patients who had surgery. In
      the domains of itch, discolouration, analgesia use, ankle swelling, cosmetic
      concern due to their varicose veins and reporting that their varicose veins
      affect their choice of clothing, there was a statistically significant difference
      favouring RFA in female patients. Conversely, in men, there was a statistically
      significant difference in favour of conventional surgery in the domains of pain,
      itch, analgesia use, cosmetic concern, affecting choice of clothing and affecting
      daily activities. There was no statistically significant difference in the mean
      AVVQ scores. CONCLUSIONS: This study has shown that for the female patients in
      our patient population, RFA results in generally better quality-of-life scores
      than conventional surgery when assessed using the disease-specific AVVQ. In this
      cohort, there was a statistically significant difference favouring conventional
      surgery in men. A number of potentially confounding variables have been
      discussed.

PMID- 23543416
TI  - What is the rate of methicillin-resistant Staphylococcus aureus and Gram-negative
      infections in open fractures?
AB  - BACKGROUND: There have been increasing reports of methicillin-resistant
      Staphylococcus aureus (MRSA) infections in the community, but it is unclear
      whether infectious organisms in open fracture infections have changed and if our
      current regimen of antibiotic prophylaxis is therefore obsolete.
      QUESTIONS/PURPOSES: We determined the recent incidence of MRSA and Gram-negative
      organism infections after open fractures. METHODS: We performed a retrospective
      cohort study on 189 patients with 202 open fractures treated from 2009 to 2010.
      During the followup, patients were evaluated for signs of infection using the
      Centers for Disease Control and Prevention criteria. We determined the organisms
      using routine microbiology culture. The minimum followup was 3 months (median, 47
      months; range, 3-108 months). RESULTS: Of the 202 open fractures, 20 (10%)
      developed infections. The most common organism was Staphylococcus, whereas five
      (25%) of those infected were positive for MRSA, and 11 (55%) of those with
      infection were cultured for at least one Gram-negative organism. Six (30%) open
      fractures had infections that grew out multiple organisms. The incidence of MRSA
      infections in our open fracture population was 2.5%. CONCLUSIONS: There is a high
      incidence of MRSA and Gram-negative infections after open fractures, which may
      indicate that current antibiotic regimens need to be changed. LEVEL OF EVIDENCE:
      Level IV, retrospective case-series. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 23543418
TI  - Reason for revision TKA predicts clinical outcome: prospective evaluation of 150
      consecutive patients with 2-years followup.
AB  - BACKGROUND: There is limited knowledge regarding the relationship between the
      reason for revising a TKA and the clinical outcome in terms of satisfaction,
      pain, and function with time. QUESTIONS/PURPOSES: In a cohort of patients
      receiving a fully revised TKA, we hypothesized (1) outcomes would differ
      according to reason for revision at 2 years, (2) outcomes would improve gradually
      during those 2 years, (3) rates of complications differ depending on the reason
      for revision, and (4) patients with complications have lower scores. METHODS: We
      studied a prospective cohort of 150 patients receiving a fully revised TKA using
      a single implant system in two high-volume centers at 24 months of followup. VAS
      satisfaction, VAS pain, The Knee Society Scoring System((c)) (KSS) clinical and
      functional scores, and complication rate were correlated with their reasons for
      revision, including septic loosening, aseptic loosening, component malposition,
      instability, and stiffness. RESULTS: The aseptic loosening group showed better
      outcomes compared with the instability, malposition, and septic loosening groups,
      which showed intermediate results (p < 0.05). The stiffness group performed
      significantly worse on all outcome measures. The outcome for patients with a
      complication, after treatment of the complication, was less favorable.
      CONCLUSIONS: The reason for revision TKA predicts clinical outcomes.
      Satisfaction, pain reduction, and functional improvement are better and
      complication rates are lower after revision TKA for aseptic loosening than for
      other causes of failure. For component malposition, instability, and septic
      loosening groups, there may be more pain and a higher complication rate. For
      stiffness, the outcomes are less favorable in all scores. LEVEL OF EVIDENCE:
      Level III, prognostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 23543417
TI  - Scheduled analgesic regimen improves rehabilitation after hip fracture surgery.
AB  - BACKGROUND: Postoperative pain often is the limiting factor in the rehabilitation
      of patients after hip fracture surgery. QUESTIONS/PURPOSES: We compared an
      approach using scheduled analgesic dosing with as-needed analgesic dosing in
      patients after hip fracture surgery, to compare these approaches in terms of (1)
      resting and dynamic pain intensity, (2) postoperative patient mobility, and (3)
      functional end points. METHODS: We conducted a prospective cohort study of 400
      patients who underwent surgical treatment of hip fractures at our hospital. The
      groups were formed sequentially, such that the first 200 patients formed the
      intervention group (treated with scheduled analgesic intake for the first 3 weeks
      after surgery), and the next 200 patients were the control group (treated using a
      protocol of analgesic administration on request). Resting and dynamic pain
      intensity, mobility, and functional performance were compared between the two
      analgesic protocols. RESULTS: As expected, analgesic consumption was lower in the
      control group (tramadol doses, 27 versus 63; paracetamol doses, 29 versus 63).
      Despite the large difference in the amounts of analgesics consumed, resting and
      dynamic pain intensity showed improvement in each group and there was no
      difference between groups in terms of postoperative pain. However, there was a
      positive correlation between functional outcomes and analgesic consumption in the
      control group. The intervention group achieved higher functional performance on
      discharge (elderly mobility scale, 11 versus 8; functional independence measure,
      88 versus 79). On discharge, fewer patients in the intervention group were
      wheelchair ambulators (3 versus 32), meaning more patients in the intervention
      group were able to walk. CONCLUSIONS: The study showed that a scheduled analgesic
      intake can improve the functional outcomes of patients with geriatric hip
      fractures after surgery. LEVEL OF EVIDENCE: Level II, therapeutic study. See the
      guidelines for authors for a complete description of levels of evidence.

PMID- 23543419
TI  - High survivorship with a titanium-encased alumina ceramic bearing for total hip
      arthroplasty.
AB  - BACKGROUND: Although ceramic-on-ceramic bearings for total hip arthroplasty (THA)
      show promising results in terms of bearing-surface wear, fracture of the bearing,
      insertional chips, and squeaking remain a concern. QUESTIONS/PURPOSES: Our
      primary objective of this report was to determine overall survivorship of a
      titanium-encased ceramic-on-ceramic bearing couple. Our secondary objectives were
      to evaluate for ceramic fracture, insertional chips, osteolysis, and device
      squeaking. METHODS: Six surgeons at six institutions implanted 194 patients (209
      hips) with an average age of 52 years with cementless hips and alumina ceramic
      bearings. One hundred thirty-seven patients (146 hips) have 10-year followup
      (70%). We determined Kaplan-Meier survivorship of the bearing surface and implant
      system and collected radiographic and clinical data to evaluate for osteolysis
      and squeaking. RESULTS: Survivorship using revision for any reason as the end
      point was 97% at 10 years and survivorship end point bearing surface failure or
      aseptic loosening of 99%. There was one ceramic insert fracture (0.5%), there
      were no insertional chips, there was no visible osteolysis on AP and lateral
      radiographs, and there was a 1% patient-self-reported incidence of squeaking at
      the last clinical followup. Six hips underwent revision (3.7%). CONCLUSIONS:
      Ceramic bearings for THA with a titanium-encased insert have high survivorship at
      10 years followup and a fracture risk of 0.5%. We found at last followup on
      routine radiographs no evidence of osteolysis, and no patient has been revised
      for squeaking or has reported dissatisfaction with the clinical result because of
      noise. IV, therapeutic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 23543420
TI  - The orthopaedist's role in healthcare system governance.
AB  - BACKGROUND: Historically, physicians as participants in healthcare governance
      were shunned because of perceived potential for conflict of interest. This maxim
      is being revisited as health systems begin to appreciate the value presented by
      physician leaders. QUESTIONS/PURPOSES: This overview of the orthopaedist's role
      in healthcare governance will be addressed in three sections: first to identify
      the need for change in American healthcare, second to examine the role that
      physicians should play in governing over this inevitable change, and third to
      outline strategies for effective participation for those physicians wishing to
      play a role in healthcare governance. METHODS: The PubMed data set was queried
      applying the search commands "governance AND (healthcare OR hospital) AND (doctor
      OR physician OR surgeon)" for the time period 1969 to 2012. In addition, the
      bibliographies of relevant articles were reviewed. This search strategy returned
      404 titles. Abstract and article review identified 19 relevant to the topic.
      Bibliographic review identified five more articles of relevance forming the
      foundation for this review. RESULTS: The delivery of American health care will
      require change to face current economic realities. Organizations that embrace
      this change guided by the insight of physician governors are well positioned to
      recognize the simultaneous improvement in value and quality. Although few
      physicians are formally trained for these roles, multiple paths to becoming
      effective governors are available. CONCLUSIONS: In this environment of rapid
      change in healthcare delivery, the medical insight of physician leadership will
      prove invaluable. Governing bodies should reach out to talented physicians and
      administratively talented physicians should rise to this challenge.

PMID- 23543421
TI  - Statistical validity and clinical merits of a new civilian gunshot injury
      classification.
AB  - BACKGROUND: Despite the high prevalence of civilian gunshot injuries (GSIs) in
      the United States, no universally accepted classification currently exists.
      Recently, two of us (ZG, RWL) proposed a GSI classification based on energy
      transferred, vital structure damage, wound characteristics, fracture, and degree
      of contamination. This classification has not been validated in a clinical
      setting. QUESTIONS/PURPOSES: We determined the feasibility, internal consistency,
      and predictive accuracy of this classification. METHODS: We reviewed the medical
      records of 216 patients with 264 GSIs treated at a Level I trauma center.
      Feasibility was determined by the investigators' ability to retrospectively
      complete the classification system based on patient information routinely
      collected in medical records. Internal consistency was determined using
      Cronbach's coefficient alpha. Predictive accuracy was constructed and interpreted
      in a receiver operating characteristic (ROC) curve using all the classification
      components to predict GSI severity. The clinical management/outcome (deceased,
      hospitalization versus nonadmission, and surgical versus nonsurgical treatment)
      was used as a proxy measure of GSI severity. RESULTS: We were able to apply the
      classification to 82% of charts we reviewed. The classification components
      appeared to be internally consistent (Cronbach's alpha was 0.69 and was increased
      to 0.78 after exclusion of contamination). Each component was associated with
      clinical management. GSI classified as high energy, worse vital structure, and
      high contamination had higher rates of surgery (84%, 84%, and 100%,
      respectively). The area under the ROC curve was 0.80, suggesting the
      classification can accurately describe GSI severity. CONCLUSIONS: Our results
      suggest this new civilian GSI classification is statistically valid and has
      clinical merits warranting further investigation in the setting of a prospective
      trial.

PMID- 23543423
TI  - Letter transpositions within and across morphemic boundaries: is there a cross
      language difference?
AB  - Research on the impact of letter transpositions that arise across morpheme
      boundaries has yielded conflicting results. These results have led to the
      suggestion that a cross-linguistic difference may exist in the recognition of
      Spanish and English words. In two masked-priming experiments run on separate
      groups of Spanish and English speakers, we tested this hypothesis by comparing
      the impacts of primes with letter transpositions that arose within morphemes or
      across morpheme boundaries on the recognition of identical or near-identical
      Spanish-English cognate targets. The results showed transposed-letter benefits in
      both Spanish and English that were not modulated by the position of the
      transposed letter in the prime stimulus. Our findings therefore add to the
      growing body of literature suggesting that the transposed-letter benefit is not
      affected by the position of the transposed letters relative to the morpheme
      boundary, and they dispel previous suggestions that there might be a genuine
      difference in orthographic coding across the Spanish and English writing systems.

PMID- 23543424
TI  - Psychopathy, adaptation, and disorder.
AB  - In a recent study, we found a negative association between psychopathy and
      violence against genetic relatives. We interpreted this result as a form of
      nepotism and argued that it failed to support the hypothesis that psychopathy is
      a mental disorder, suggesting instead that it supports the hypothesis that
      psychopathy is an evolved life history strategy. This interpretation and
      subsequent arguments have been challenged in a number of ways. Here, we identify
      several misunderstandings regarding the harmful dysfunction definition of mental
      disorder as it applies to psychopathy and regarding the meaning of nepotism.
      Furthermore, we examine the evidence provided by our critics that psychopathy is
      associated with other disorders, and we offer a comment on their alternative
      model of psychopathy. We conclude that there remains little evidence that
      psychopathy is the product of dysfunctional mechanisms.

PMID- 23543425
TI  - Injury patterns in Swedish elite athletics: annual incidence, injury types and
      risk factors.
AB  - OBJECTIVE: To estimate the incidence, type and severity of musculoskeletal
      injuries in youth and adult elite athletics athletes and to explore risk factors
      for sustaining injuries. DESIGN: Prospective cohort study conducted during a 52
      week period. SETTING: Male and female youth and adult athletics athletes ranked
      in the top 10 in Sweden (n=292). RESULTS: 199 (68%) athletes reported an injury
      during the study season. Ninety-six per cent of the reported injuries were non
      traumatic (associated with overuse). Most injuries (51%) were severe, causing a
      period of absence from normal training exceeding 3 weeks. Log-rank tests revealed
      risk differences with regard to athlete category (p=0.046), recent previous
      injury (>3 weeks time-loss; p=0.039) and training load rank index (TLRI;
      p=0.019). Cox proportional hazards regression analyses showed that athletes in
      the third (HR 1.79; 95% CI 1.54 to 2.78) and fourth TLRI quartiles (HR 1.79; 95%
      CI 1.16 to 2.74) had almost a twofold increased risk of injury compared with
      their peers in the first quartile and interaction effects between athlete
      category and previous injury; youth male athletes with a previous serious injury
      had more than a fourfold increased risk of injury (HR=4.39; 95% CI 2.20 to 8.77)
      compared with youth females with no previous injury. CONCLUSIONS: The injury
      incidence among both youth and adult elite athletics athletes is high. A training
      load index combing hours and intensity and a history of severe injury the
      previous year were predictors for injury. Further studies on measures to quantify
      training content and protocols for safe return to athletics are warranted.

PMID- 23543426
TI  - Comparison of the therapeutic effectiveness of sustained low-efficiency dialysis
      (SLED) with continuous blood purification (CBP) in critically ill patients.
AB  - The differences in therapeutic effectiveness between sustained low-efficiency
      dialysis (SLED) and continuous blood purification (CBP) were investigated. In
      order to assess the different treatment methods, 56 critically ill patients were
      divided into two groups, the CBP group and the SLED group. A comparison was made
      between all the biochemical indicators, in-hospital duration, hemodynamic
      parameters, acute physiology and chronic health evaluation (APACHE-II), the
      survival, and the mortality rates. After treatment, the levels of serum creatine
      kinase isozyme MB (CK-MB), creatine kinase, creatinine, glutamate-oxalacetate
      transaminase (AST), glutamate-pyruvate transaminase (ALT), APACHE II score on the
      1st, 2nd, and 7th day in both the treatment groups were lower than that before
      the treatment (P < 0.05). There are no statistical differences in in-hospital
      duration, biochemical indicators, APACHE II score, hemodynamic parameters, the
      survival rate and the mortality rate between the two groups (P > 0.05). It was
      concluded that SLED has similar hemodynamic stability with CBP and the two
      methods have similar treatment effects in critically ill patients. However, we
      noticed that SLED can be relatively economical and convenient for critically ill
      patients in clinical practice.

PMID- 23543427
TI  - Elderly patients and coronary heart disease on response to treadmill exercise
      test.
AB  - To study the response of the cardiovascular system, to exercise tolerance in
      patients over 75 years old with coronary heart disease (CHD), and to evaluate the
      significance of the parameters of the treadmill exercise test (TET). 110 patients
      received TET and coronary artery angiography. They were divided into two groups:
      the elderly patients group included 50 patients over 75 years old, and the
      control group included 60 patients under 60 years old. (1) With aging, there were
      much more CHD patients in the positive TET (P < 0.05) than in the negative TET (P
      > 0.05). (2) The parameters of TET for the elderly CHD patients group, included
      exercise time, peak heart rate, and the onset of ST depression, were lower than
      the control group (P < 0.05). There was no statistical significance between the
      two groups in the extent and duration of ST depression (P < 0.05). (1) In TET,
      the elderly patients had the higher diagnostic value on CHD. (2) The elderly
      patients with CHD had the lower endurance to exercise test.

PMID- 23543428
TI  - Tuberoserpiginous lesions in a 50-year-old patient with hand eczema: a quiz case.

PMID- 23543429
TI  - High-throughput screening for small-molecule inhibitors of Staphylococcus
      epidermidis RP62a biofilms.
AB  - High-throughput screening (HTS) of 42 865 compounds was performed to identify
      compounds that inhibit formation of or kill Staphylococcus epidermidis RP62a
      biofilms. Three biological processes were assayed, including (1) growth of
      planktonic/biofilm bacteria, (2) assessment of metabolically active biofilm
      bacteria using a resazurin assay, and (3) assessment of biofilm biomass by
      crystal violet staining. After completing the three tiers (primary screening, hit
      confirmation, and dose-response curves), 352 compounds (representing ~0.8%) were
      selected as confirmed hit compounds from the HTS assay. The compounds were
      divided into groups based on their effectiveness on S. epidermidis biofilm
      properties. The majority of these affected both inhibition and killing of
      bacterial biofilm cultures. Only 16 of the confirmed hit compounds that have
      either an AC50 lower than 10 uM and/or Sconst >=70 from those processed were
      selected for further study by confocal laser scanning microscopy (CLSM). The CLSM
      was used to evaluate the confirmed hit compounds on (1) inhibition of biofilm
      formation and (2) killing of preexisting S. epidermidis biofilms. Taken together,
      with further testing (e.g., disease-related conditions), such compounds may have
      applications as broad antimicrobial/antibiofilm use for prophylactic or
      therapeutic intervention to combat infections in surgical and intensive care
      clinics and battlefield settings. 

PMID- 23543430
TI  - Development of a novel beta-secretase binding assay using the AlphaScreen
      platform.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting
      millions of people. beta-secretase-1 (BACE1), an enzyme involved in the
      processing of the amyloid precursor protein (APP) to form Abeta is a validated
      target for AD. Herein, the authors develop and validate a novel binding assay for
      BACE1 using the AlphaScreen platform that is amenable for high-throughput
      screening (HTS). Small-molecule BACE1 inhibitors of the hydroxyethylamine,
      hydantoin, and sulfamide classes were functionalized by biotin PEG linkers of
      varying lengths forming probes that were bound to streptavidin donor beads. BACE1
      was coupled to nickel-chelate acceptor beads. Upon mixing, probes designed from
      all three classes registered high signal-to-background values in the AlphaScreen
      binding assay, where the interaction between probe and BACE1 was completely
      blocked by free parent compound. A probe from the hydantoin class was chosen for
      further optimization, where the final assay conditions of 50 nM BACE and 250 nM
      probe were used and Z(') values >0.75 were commonly observed. IC50 values
      determined by the AlphaScreen assay format exhibited ~10-fold greater sensitivity
      when compared with a fluorescence polarization-based activity assay. The assay
      was miniaturized to a 1536-well format for HTS, in which 525 000 compounds were
      screened. 

PMID- 23543431
TI  - Development of a small-molecule screening method for inhibitors of cellular
      response to myostatin and activin A.
AB  - Myostatin, a member of the transforming growth factor (TGF)-beta family of
      secreted ligands, is a strong negative regulator of muscle growth. As such,
      therapeutic inhibitors of myostatin are actively being investigated for their
      potential in the treatment of muscle-wasting diseases such as muscular dystrophy
      and sarcopenia. Here, we sought to develop a high-throughput screening (HTS)
      method for small-molecule inhibitors that target myostatin. We created a HEK293
      stable cell line that expresses the (CAGA)12-luciferase reporter construct and
      robustly responds to signaling of certain classes of TGF-beta family ligands.
      After optimization and miniaturization of the assay to a 384-well format, we
      successfully screened a library of compounds for inhibition of myostatin and the
      closely related activin A. Selection of some of the tested compounds was directed
      by in silico screening against myostatin, which led to an enrichment of target
      hits as compared with random selection. Altogether, we present an HTS method that
      will be useful for screening potential inhibitors of not only myostatin but also
      many other ligands of the TGF-beta family. 

PMID- 23543432
TI  - Macroprolactinemia in hyperprolactinemic infertile women.
AB  - Hyperprolactinemia occurs in 15-20 % of women with menstrual disturbances and 30
      40 % of infertile women and it can adversely affect the fertility. High molecular
      weight prolactin (macroprolactin) has long been known in hyperprolactinemic
      fertile women. However, the prevalence of macroprolactinemia in
      hyperprolactinemic infertile women is not known. This cross-sectional study was
      carried out during the period of June 2010 and June 2011 at a single tertiary
      care centre. All women who attended the infertility clinic during this period
      were screened for hyperprolactinemia and only women with hyperprolactinemia and
      infertility were further studied for the presence of macroprolactin by
      polyethylene glycol precipitation assay. We compared the clinical, hormonal
      profile and fertility outcome of infertile women with true hyperprolactinemia and
      macroprolacinemia using appropriate statistical tests. Of 1,163 infertile women,
      183 (15.7 %) had hyperprolactinemia [134 (73 %) had primary infertility and 49
      (27 %) had secondary infertility]. Out of these 183 women with
      hyperprolactinemia, one had microadenoma, 161 had true idiopathic
      hyperprolactinemia and 21 (11.5 %) women had macroprolactinemia. The prevalence
      of oligomenorrhea and galactorrhea were significantly higher in patients with
      true hyperprolactinemia than macroprolactinemia (46 vs. 14 %, p < 0.008 and 30
      vs. 5 %, p = 0.01 respectively). Twenty-two patients (13.5 %) of true
      hyperprolactinemia and two (9 %) in macroprolactinemia became pregnant during the
      study period. Prolactin measurement should be a part of routine evaluation of
      couples referred to infertility clinics. Macroprolactin screening is mandatory
      when clinical features and serum PRL assay results are conflicting. Patients with
      macroprolactinemia should be investigated for causes of infertility other than
      hyperprolactinemia.

PMID- 23543433
TI  - Gene polymorphisms and thyroid function in patients with heart failure.
AB  - We evaluated nuclear factor kappa B {NFkB, rs28362491 [-94ins/delATTG (W/D)]} and
      angiotensin converting enzyme {ACE; rs1799752 [Ins(I)/Del(D)]} gene polymorphisms
      and their correlation with thyroid function in patients with heart failure (HF).
      Peak oxygen uptake (VO(2)) was evaluated (by Weber classification) during a
      symptom-limited cardiopulmonary exercise test in 194 patients. Thyroid
      stimulating hormone, triiodothyronine (T3), thyroxine (T4), and free (F) T3 and
      FT4 were also measured. According to their cardiovascular (CV) capacity, patients
      were subdivided into four groups: group A included patients with peak VO(2) >20
      ml/kg/min, group B 16-20 ml/kg/min, group C 10-16 ml/kg/min, and group D 6-10
      ml/kg/min. Patients were also genotyped for NFkB and ACE genetic variants. T3 was
      increased and FT3 was decreased for every raise in Weber's classification (p =
      0.007 and p = 0.012, respectively). Del carriers had elevated FT3 levels compared
      with Ins carriers (p = 0.021). Patients with II genotype had elevated T4 levels
      compared with ID genotype (p = 0.044). Both T4 and FT4 were decreased in D allele
      carriers (p = 0.007 and p = 0.045, respectively). Thyroid hormones correlated
      with CV capacity. Associations between the NFkB and ACE gene polymorphisms and
      thyroid hormones levels were also observed. Further larger studies are required
      to clarify genes contribution in HF.

PMID- 23543435
TI  - Severe polymyositis due to Toxoplasma gondii in an adult immunocompetent patient:
      a case report and review of the literature.
AB  - Toxoplasmosis, a worldwide zoonosis caused by a coccidian parasite Toxoplasma
      gondii, is more often asymptomatic in immunocompetent patients. We report the
      case of a 38-year-old immunocompetent male with a polymyositis as the presenting
      manifestation of T. gondii infection. The patient was hospitalized for a 30-day
      history of fever (T max 39.5 degrees C), muscle pain, and progressive weakness of
      the muscles. A diagnosis of polymyositis was made, and he was started on
      corticosteroid treatment, which caused no reduction of symptoms. After finding a
      positive polymerase chain reaction (PCR) assay for T. gondii, together with
      additional clinical findings, a diagnosis of acute toxoplasmosis was made.
      Specific treatment with pyrimethamine and sulfadiazine was started, with a
      progressive reduction of symptoms and normalization of laboratory tests. 

PMID- 23543436
TI  - A survey of methicillin-resistant Staphylococcus aureus control strategies in
      Italy.
AB  - PURPOSE: Data regarding the implementation of state-of-the-art methicillin
      resistant Staphylococcus aureus (MRSA) control procedures in Italy are lacking.
      There is a need to evaluate compliance with MRSA recommendations (CR) in Italian
      hospitals. METHODS: A 67-question closed-answer survey was sent to all Italian
      hospitals, in order to analyze and evaluate program consistency with CR [hand
      hygiene (HH), contact precautions, screening of high-risk patients,
      decolonization, feedback on surveillance data, and antimicrobial guidelines and
      education programs]. RESULTS: 205 hospitals, which account for 42 % of national
      admissions, returned questionnaires. 131 hospitals (64 %) did not have written
      MRSA control guidelines. Hospitals reported the following levels of compliance
      with CR: (1) HH: 67 hospitals (33 %); (2) contact precautions: 33 (16 %); (3)
      MRSA screening: 66 (32 %); (4) MRSA decolonization: 42 (20 %); (5) surveillance
      data feedback: 87 (43 %); and (6) antimicrobial guidelines and education
      programs: 41 (20 %). One hospital (0.5 % of responses) had implemented all
      recommendations and 28 hospitals (14 %) had implemented four or five
      recommendations. 31 % of hospitals surveyed had implemented none. Multivariate
      analysis showed that the only factor identified as being associated with the
      implementation of MRSA control recommendations was the number of meetings/year of
      the infection control team (ICT) (p = 0.004). CONCLUSIONS: Written MRSA control
      guidelines are available in only one-third of Italian facilities. An organized
      system, with >=4 interventions, has been implemented in just 1 out of 7
      hospitals. HH programs and ICT activity are related to better MRSA control. In
      Italy, there is significant opportunity for improvement in MRSA control.

PMID- 23543437
TI  - Unveiling signaling events in root responses to strigolactone.

PMID- 23543434
TI  - Diabetes-associated macrovascular complications: cell-based therapy a new tool?
AB  - Diabetes mellitus and its ongoing macrovascular complications represent one of
      the major health problems around the world. Rise in obesity and population ages
      correlate with the increased incidence of diabetes. This highlights the need for
      novel approaches to prevent and treat this pandemic. The discovery of a reservoir
      of stem/progenitors in bone marrow and in mesenchymal tissue has attracted
      interest of both biologists and clinicians. A number of preclinical and clinical
      trials were developed to explore their potential clinical impact, as target or
      vehicle, in different clinical settings, including diabetes complications.
      Currently, bone marrow, peripheral blood, mesenchymal, and adipose tissues have
      been used as stem/progenitor cell sources. However, evidences have been provided
      that both bone marrow and circulating progenitor cells are dysfunctional in
      diabetes. These observations along with the growing advantages in genetic
      manipulation have spurred researchers to exploit ex vivo manipulated cells to
      overcome these hurdles. In this article, we provide an overview of data relevant
      to stem-progenitors potential clinical application in revascularization and/or
      vascular repair. Moreover, the hurdles at using progenitor cells in diabetic
      patients will be also discussed. 

PMID- 23543438
TI  - Heteromeric and homomeric geranyl diphosphate synthases from Catharanthus roseus
      and their role in monoterpene indole alkaloid biosynthesis.
AB  - Catharanthus roseus is the sole source of two most important monoterpene indole
      alkaloid (MIA) anti-cancer agents: vinblastine and vincristine. MIAs possess a
      terpene and an indole moiety derived from terpenoid and shikimate pathways,
      respectively. Geranyl diphosphate (GPP), the entry point to the formation of
      terpene moiety, is a product of the condensation of isopentenyl diphosphate (IPP)
      and dimethylallyl diphosphate (DMAPP) by GPP synthase (GPPS). Here, we report
      three genes encoding proteins with sequence similarity to large subunit
      (CrGPPS.LSU) and small subunit (CrGPPS.SSU) of heteromeric GPPSs, and a homomeric
      GPPSs. CrGPPS.LSU is a bifunctional enzyme producing both GPP and geranyl geranyl
      diphosphate (GGPP), CrGPPS.SSU is inactive, whereas CrGPPS is a homomeric enzyme
      forming GPP. Co-expression of both subunits in Escherichia coli resulted in
      heteromeric enzyme with enhanced activity producing only GPP. While CrGPPS.LSU
      and CrGPPS showed higher expression in older and younger leaves, respectively,
      CrGPPS.SSU showed an increasing trend and decreased gradually. Methyl jasmonate
      (MeJA) treatment of leaves significantly induced the expression of only
      CrGPPS.SSU. GFP localization indicated that CrGPPS.SSU is plastidial whereas
      CrGPPS is mitochondrial. Transient overexpression of AmGPPS.SSU in C. roseus
      leaves resulted in increased vindoline, immediate monomeric precursor of
      vinblastine and vincristine. Although C. roseus has both heteromeric and
      homomeric GPPS enzymes, our results implicate the involvement of only heteromeric
      GPPS with CrGPPS.SSU regulating the GPP flux for MIA biosynthesis. 

PMID- 23543439
TI  - Regulation of stamen development by coordinated actions of jasmonate, auxin, and
      gibberellin in Arabidopsis.
AB  - Proper stamen development is essential for plants to achieve their life cycles.
      Defects in stamen development will cause male sterility. A vast array of research
      efforts have been made to understand stamen developmental processes and
      regulatory mechanisms over the past decades. It is so far reported that
      phytohormones, including jasmonate, auxin, gibberellin, brassinosteroid, and
      cytokinin, play essential roles in regulation of stamen development. This review
      will briefly summarize the molecular basis for coordinated regulation of stamen
      development by jasmonate, auxin, and gibberellin in Arabidopsis. 

PMID- 23543440
TI  - Effects of black seed oil on resolution of hepato-renal toxicity induced
      bybromobenzene in rats.
AB  - OBJECTIVE: Volatile halocarbon, bromobenzene (BB), is frequently encountered in
      table-ready foods as contaminants residues. The objective of this study was to
      investigate whether black seed oil could attenuate hepato-renal injury induced by
      BB exposure. MATERIALS AND METHODS: The evaluation was done through measuring
      liver oxidative stress markers: reduced glutathione (GSH), superoxide dismutase
      (SOD) and malondialdehyde (MDA). Hepatic succinate dehydrogenase (SDH), lactate
      dehydrogenases (LDH) and glucose-6-phosphatase (G-6-Pase) were estimated. Serum
      aspartate and alanine aminotransferases (AST, ALT) and alkaline phosphatase were
      also evaluated. Kidney function indices; blood urea nitrogen (BUN), creatinine,
      serum protein, nitric oxide (NO), Na-K-adenosine triphosphatase (Na+-K+-ATPase)
      and phospholipids were done. Liver and kidney histopathological analysis and
      collagen content were analyzed for results confirmation. RESULTS: Treatment with
      black seed oil (BSO) alleviated the elevation of GSH, SDH, LDH, G-6-Pase, serum
      protein, NO, Na+-K+-ATPase, phospholipids levels and attenuated MDA, SOD, AST,
      ALT and ALP. Diminution of collagen content and improvement in liver and kidney
      architectures were observed. CONCLUSIONS: BSO enhanced the hepato-renal
      protection mechanism, reduced disease complications and delayed its progression.
      Further studies are needed to identify the molecules responsible for its
      pharmacological effect.  

PMID- 23543441
TI  - Quercetin potentially attenuates cadmium induced oxidative stress mediated
      cardiotoxicity and dyslipidemia in rats.
AB  - BACKGROUND: Cadmium is one of the potent cardiotoxic heavy metals in the
      environment, which induces oxidative stress, dyslipidemia and membrane
      disturbances in heart. Quercetin is an effective antioxidant and free radical
      scavenger against oxidative stress. This study was designed to evaluate the
      protective effect of quercetin (QE) on cardiac marker enzymes, lipid peroxidation
      products, lipid profile, membrane bound ATPases and antioxidant status in cadmium
      (Cd)-intoxicated rats. MATERIALS AND METHODS: Twenty four male albino rats were
      used. Cadmium induced oxidative cardiotoxicity was induced by the oral
      administration of Cd for four weeks. Quercetin  was pretreated along with Cd for
      four weeks to assess its cardioprotective effect against Cd intoxication. Rats
      treated with vehicles alone were used as controls. RESULTS: Rats intoxicated with
      cadmium (5 mg/kg/day) for 4 weeks in combination with quercetin (50 mg/kg/day)
      respectively. Cd-induced cardiotoxicity and dyslipidemia was indicated by
      increased activities of marker enzymes such as creatine kinase-MB, aspartate
      transaminase, alanine transaminase, alkaline phosphatase and lactate
      dehydrogenase in serum. In addition, the levels of lipid peroxidation products
      and protein carbonyl contents in heart were significantly (p < 0.05) increased
      and the activities of enzymic antioxidants such as superoxide dismutase,
      catalase, glutathione peroxidase, glutathione reductase and glutathione-S
      transferase in the heart and non-enzymic antioxidants such as glutathione,
      vitamin C and E in the heart were significantly (p < 0.05) decreased in Cd
      intoxicated rats. The levels total cholesterol (TC), triglycerides (TG),
      phospholipidis (PL), free fatty acids (FFA), LDL and VLDL were significantly (p <
      0.05) increased and the level of HDL was significantly decreased in the serum of
      Cd-treated rats. Cd intoxication also increased the levels of TC, TG and FFA and
      decreased the level of PL in the heart tissue. Further Cd treatment significantly
      (p < 0.05) decreased the levels of membrane bound ATP ases in heart. QE treatment
      along with Cd showed significant protective effect on all the biochemical
      parameters studied. Histopathological findings of QE and Cd treated heart
      confirmed the biochemical findings of this study. Thus, QE protects the
      myocardium against Cd-induced oxidative stress and dyslipidemia in rats.
      CONCLUSIONS: Quercetin may be beneficial in combating the cadmium induced
      oxidative cardiotoxicity and dyslipidemia in rats.  

PMID- 23543442
TI  - Chemokines fluctuate in the progression of primary breast cancer.
AB  - BACKGROUND: Many studies have demonstrated that chemokines and their receptors
      play important roles in breast cancer. However, few of them focus on the
      concentration change of chemokines along breast cancer evolvement, especially for
      primary breast cancer. PURPOSE OF THE STUDY: To investigate the effects of
      chemokines and their receptors on different stage of primary breast cancer, and
      to find correlationships between chemokines, between different clinico
      pathological characters of patients or between chemokines and different clinico
      pathological characters of patients. PATIENTS AND METHODS: We evaluated and
      compared the concentration of 10 chemokines and receptors in serum of patients
      diagnosed as breast benign change, epithelial proliferation (present only or with
      atypia), in situ carcinoma and invasive carcinoma. RESULTS: Our oneway ANOVA
      analysis results showed that in all cases from benign diseases to invasive
      carcinoma, the concentration of CXCL8, CXCR4 and CXCL12 was significantly
      different; in benign subgroups (benign change, benign change with proliferation,
      atypia), the concentration of CCL2 and CCR5 was significantly different; in
      invasive carcinoma cases, DARC concentration was significantly correlated with
      the relapse risk of patients. CONCLUSIONS: The correlation analysis indicated the
      great crosstalk between chemokines and receptors in the course of primary breast
      cancer; Ki67 expression was associated with CXCL5 and CXCL7 concentration; tumor
      size was associated with CXCL8 concentration; and the correlation analysis
      between clinico-pathological characters of patients showed that pathological
      diagnosis was correlated with tumor size, relapse risk and Ki67 expression;
      nuclear grades was correlated with LN metastasis, ER status, PR status and the
      breast cancer genotype; LN metastasis was correlated with relapse risk. Our
      findings clearly indicated for the first time that the fluctuations of chemokines
      and receptors contributed to the evolving of primary breast cancer.

PMID- 23543443
TI  - Relaxin enhances in-vitro invasiveness of breast cancer cell lines by
      upregulation of S100A4/MMPs signaling.
AB  - OBJECTIVES: Relaxin (RLX or RLN) levels are increased in cases of human breast
      cancer and has been shown to promote cancer cell migration in carcinoma cells of
      the breast; however, the cellular mechanisms of relaxin exposure in breast cancer
      cells are not fully understood. In human breast cancer cells, relaxin was shown
      to downregulate the metastasis-promoting protein S100A4, a highly significant
      prognostic factor for poor survival in breast cancer patients. RLX was also found
      to enhance in-vitro invasiveness of breast cancer cell lines by induction of
      matrix metalloproteinases (MMPs) expression. The aim of this study was to
      investigate the effects of relaxin on breast cancer cell invasion by S100A4
      dependent MMPs pathway. MATERIALS AND METHODS: The human breast cancer MDA-MB-231
      cells were treated with 100-500 ug/L porcine RLX, or/and transfected with S100A4
      siRNA (20 ng), or/and treated with MMPs inhibitor FN439 (0.3 nM). RESULTS: We
      observed that incubation with porcine RLX increases in-vitro cell invasion and in
      vitro invasiveness. Enhanced invasiveness was accompanied by up-regulation of
      S100A4 and MMP-2 and MMP-9. The relaxin-induced increase in cell invasion was
      blocked almost when S100A4 expression was diminished using an S100A4 small
      interfering RNA knockdown approach or when MMPs was inhibited by MMPs inhibitor
      FN439. The relaxin-induced increase in MMP-2 and MMP-9 expression was blocked
      when S100A4 was inhibited by S100A4 siRNA transfection. CONCLUSIONS: Our data
      demonstrate that the RLX controls the in-vitro invasive potential of human breast
      cancer cells through S100A4 dependent MMPs regulation.

PMID- 23543444
TI  - The PPI network and cluster ONE analysis to explain the mechanism of bladder
      cancer.
AB  - BACKGROUND: Bladder cancer is a common cancer worldwide whose incidence continues
      to increase. It is estimated that there are 261,000 cases of bladder cancer
      resulting in 115,000 deaths worldwide. AIM: Although some studies can be
      initiated using small local tissue collections, high quality collection of fresh
      tissues from new clinical trials will be crucial for proper evaluation of
      associations with clinical outcome. For superficial bladder cancer,
      identification of tumors that will progress has long been perceived as a
      potential application of genetic studies. MATERIALS AND METHODS: In our study, we
      constructed the Protein-Protein Interactions (PPI) network using the Cytoscape
      and detected some network modeling clusters. In addition, we enriched GO
      categories among these genes in the first cluster and detected a pathway i.e.
      Spliceosome (hsa03040). Most Gene Ontology (GO) categories and Spliceosome were
      closely to RNA splicing and cellular macromolecular complex (CMC) assembly, which
      indicates that the mutation of RNA splicing and CMC assembly maybe important
      factors causing bladder cancer. RESULTS: In our study, these clusters of
      GO:0034622, GO:0006397 and GO:0034621 in bladder cancer belong to cellular
      macromolecular complex assembly, which may play an important role in the
      occurrence of cancer cells. CONCLUSIONS: It is a great significance for the
      detection and treatment of bladder cancer to understand the mechanism of RNA
      splicing and CMC assembly.

PMID- 23543445
TI  - Tissue engineering as innovative chance for organ replacement in radical tumor
      surgery.
AB  - BACKGROUND: Different pathological conditions such as congenital organ absence,
      severe organ injuries, end-stage organ failure and malignancy-related organ
      removal, have few effective therapeutic options a part from a whole organ
      transplant, that, however, often meets with a serious shortage of suitable donor
      organs. AIM: The purpose of this paper consists in highlighting what the novel
      tissue engineering approaches might help to solve such problems. EMERGING
      CONCEPTS: A recent approach in tissue/organ engineering, particularly to build
      bioartificial airways, is the procedure of decellularizing a whole donor organ to
      obtain a complex 3D-biomatrix-scaffold maintaining the intrinsic vascular
      network, that is subsequently recellularized with recipient's autologous organ
      specific differentiated cells or/and stem cells, to build a potentially
      functional biological substitute. Such strategy has been clinically used to
      replace organ in trachea/broncus tumor patients. In another approach, mainly used
      to construct a bioartificial urinary bladder tissue, different types of either
      biodegradable synthetic polymers or naturally-derived matrices or even
      polymer/biomatrix-composite materials are used as scaffold for either cell-free
      or autologous cell-seeded tissue engineering procedures. So far, such technique
      has been mainly used to make an augmentation cystoplasty in patients with end
      stage poorly compliant neuropathic bladder or in exstrophic bladder subjects.
      FUTURE PROSPECTS: Intriguing developments in biomaterial science,
      nanotechnologies, stem cell biology, and further improvements in bioreactor
      manufacturing will allow to generate, in the near future, tissue engineered
      organs that, as for structure/function so the native one-like, might represent
      the optimum solution to replace organs in tumor surgery.

PMID- 23543446
TI  - Does living in crowded houses offer protection against the development of
      inflammatory bowel disease?
AB  - INTRODUCTION: The credibility of the "Hygiene hypothesis" in patients with
      inflammatory bowel disease has been assessed. OBJECTIVE: This survey is aimed at
      finding an answer for the question: "Does living in crowded or overcrowded houses
      protect against the development of inflammatory bowel disease?" PATIENTS AND
      METHODS: Asian immigrants to the United Kingdom who attended inflammatory bowel
      diseases' clinics during the period of the study and who fulfilled Leonard-Jones
      criteria were asked to complete a questionnaire. The participants were asked to
      respond to questions on age, sex, their birth rank, diagnosis, & number of
      brothers, sisters, sons and daughters. RESULTS: 60% of the participants had four
      or more brothers and sisters. Forty per cent of the participants grew in crowded
      houses (occupied the fourth birth rank). CONCLUSIONS: Our presented data do not
      support any role of the number of house inhabitants in the development of
      inflammatory bowel disease.

PMID- 23543447
TI  - Two years efficiency of lamivudine and adefovir dipivoxil combined therapy in
      chronic hepatitis B patients.
AB  - BACKGROUND: Lamivudine (LAM) and adefovir (ADV) are widely used in most Asian
      countries, though monotherapy is associated with the occurrence of resistance.
      AIM: To evaluate the efficiency of LAM and ADV combined treatment of chronic
      hepatitis B patients with compensated cirrhosis. PATIENTS AND METHODS: 206
      eligible Chinese patients were randomly assigned in a 1:1 ratio to receive either
      LAM or ADV for the first 24 weeks. According to virologic response at 24 weeks,
      the patients either continued to monotherapy or switched to combined therapy for
      48 weeks. After 48 weeks, all patients received LAM and ADV combined therapy for
      96 weeks. RESULTS: Serum HBV DNA levels significantly decreased in patients with
      ADV or LAM monotherapy and continuously reduced after the combined therapy. Serum
      ALT normalized rate were 88.24% and 81.37% at week 48, and 95.74% and 87.36% at
      week 96 in ADV and LAM group respectively, comparing to 60.78% and 56.73% in ADV
      and LAM groups at baseline. The accumulated virological breakthrough rate at week
      48 and 96 was significantly higher in LAM group. CONCLUSIONS: Both combination
      strategies were resulted in the long term virological, biochemical improvement in
      Chinese chronic hepatitis B patients with compensated cirrhosis.

PMID- 23543448
TI  - Decreased expression of p38 MAPK mediates protective effects of hydrogen sulfide
      on hepatic fibrosis.
AB  - AIM: To investigate the in vitro and in vivo effects of hydrogen sulfide (H2S) on
      activated hepatic stellate cells (HSCs) and carbon tetrachloride (CCl4)-induced
      hepatic fibrosis rats. To explore the in vitro and in vivo expression of Phospho
      p38, Phospho-Akt and NF-kB in HSCs treated with H2S. MATERIALS AND METHODS: HSC
      T6 cells were incubated and activated with 500 ug/L ferric nitrilotriacetate (Fe
      NTA), and then were incubated with NaHS, an H2S-releasing molecule for 6, 12, 24
      and 48 h. MTT assay was performed to detect cell viability. Propidium iodide (PI)
      staining was used to determine cell cycle by flow cytometry. Apoptosis was
      detected with Annexin-V FITC (fluorescein isothiocyanate) and PI (propidium
      iodide) double staining. Western blotting was performed to detect protein
      expressions of Phospho-p38, Phospho-Akt and NF-kB. Hepatic fibrosis model was
      established by intraperitoneal injection of CCl4 in male Wistar rats, and rats
      were randomly divided into three groups, including healthy control, rats treated
      with CCl4 + saline, and rats treated with CCl4 + NaHS. Immunohistochemistry
      analysis was performed to measure protein expression of Phospho-p38 and Phospho
      Akt in rat hepatic samples. RESULTS: NaHS inhibited the proliferation of Fe-NTA
      (nitrilotriacetic acid)-induced HSC-T6 cells in a dose-dependent way at 6, 12, 24
      and 48 h. NaHS (500 umol/L) induced G1 phase cell cycle arrest and promoted
      survival in Fe-NTA-induced HSC-T6 cells. NaHS decreased Phospho-p38 and increased
      Phospho-Akt expressions in Fe-NTA-induced HSC-T6 cells and CCl4-induced liver
      fibrosis rats. CONCLUSIONS: Exogenous H2S inhibits activated HSC-T6 cells and
      induces cell cycle arrest and apoptosis. Decreased Phospho-p38 and increased
      Phospho-Akt expressions may mediate the anti-fibrosis effect by exogenous H2S.

PMID- 23543449
TI  - Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack.
AB  - OBJECTIVES: This investigation was conducted to test the value of Neutrophil
      Lymphocyte Ratio (NLR), which has been shown in some recent studies to be a
      prognostically important and an easy-to-measure inflammatory marker, in patients
      presenting to Emergency Service with stroke (ischemic and hemorrhagic) and
      transient ischemic attack. MATERIALS AND METHODS: A total of 868 patients were
      enrolled, who presented to our Emergency Service with cerebrovascular accident
      (stroke and transient ischemic attack) and admitted to Neurology Clinic.
      Demographic characteristics and comorbidities of patients were recorded. The
      patients were divided into 3 groups as acute ischemic stroke (AIS), acute
      hemorrhagic stroke (AHS) and transient ischemic attack (TIA). Patients with AIS
      were classified into subgroups in terms of TOAST (trial of 10172 stroke
      treatment) criteria. Admission NLR levels were compared across all groups.
      RESULTS: A total of 868 patients were enrolled, 51.6% of which were male and
      48.4% were female. AIS rate was 75.3%, AHS rate was 14.3% and TIA rate was 10.7%.
      In all of patients, mortality rate was 10.7%. NLR was significantly higher in
      patients who died (p < 0.001). NLR level in patients with TIA was significantly
      lower than those of AIS and AHS groups (p < 0.001). Among AIS subgroups, NLR
      level was significantly higher in group with great artery atherosclerosis or
      atherothrombosis compared to other groups (p < 0.001). CONCLUSIONS: NLR may be
      used as a simple and easy-to-measure marker for prediction of short-term
      prognosis and in-hospital mortality in both ischemic and hemorrhagic stroke
      patients.

PMID- 23543450
TI  - Ranking antireabsorptive agents to prevent vertebral fractures in postmenopausal
      osteoporosis by mixed treatment comparison meta-analysis.
AB  - INTRODUCTION: Bisphosphonates are considered as a first-line therapy for the
      prevention and treatment of osteoporosis, showing in double-blind, randomized,
      controlled trials a significant reduction of incidence of new vertebral fractures
      compared to placebo. Recently also, Denosumab has been shown to reduce the
      appearance of new vertebral fractures by blocking RANK. There are not head to
      head comparative studies between the above mentioned drugs. Mixed treatment
      comparison, an extension of traditional meta-analysis, is able to compare
      simultaneously several drugs across a range producing a synthetic evidence of
      efficacy and a range of probability as to the best treatment. OBJECTIVES: The aim
      of this study is to simultaneously compare alendronate, risedronate, ibandronate,
      zolendronate and denosumab in the prevention of OP vertebral fractures in a
      Bayesian meta-analysis for assessing indirect comparisons. MATERIALS AND METHODS:
      A search for randomized controlled trials involving alendronate, risedronate,
      ibandronate, zolendronate and denosumab was conducted using several databases.
      Randomized controlled trials (RCTs) with a double blind treatment period of at
      least 3 years were included. Men and Glucorticoid Induced osteoporosis, RCTs
      having as primary or secondary endpoints continuous values as body mineral
      density (BMD) and studies comparing different dosing regimens of the same agent,
      which are not used in clinical practice, were excluded. Only fully published
      reports were considered. RESULTS: A total of 9 RCTs were identified providing
      data on 31,393 participants. Zolendronate had the highest probability (52%) of
      being the most effective treatment towards placebo, followed by denosumab (46%
      probability), ibandronate and then alendronate and risedronate against placebo.
      CONCLUSIONS: Although the mixed treatment comparisons among alendronate,
      risedronate, ibandronate, zolendronate and denosumab did not show a statistically
      significant difference, this analysis suggests that zolendronate, compared to
      placebo, is expected to provide the highest rate of reduction in vertebral
      fractures affecting osteoporosis affected patients.

PMID- 23543451
TI  - The antiproliferative effect of pinostrobin on human umbilical vein endothelial
      cells (HUVEC).
AB  - BACKGROUND: Atherosclerosis and stent re-stenosis are problems that are
      accompanied with high morbidity and mortality. Endothelial cell proliferation
      plays a role in both diseases, so the quest for potent inhibitors is still
      ongoing. AIM: The flavonoid pinostrobin previously showed cytotoxic effects on
      different cell lines. In this investigation, we tested the antiproliferative
      effect of pinostrobin on human umbilical vein endothelial cells (HUVEC).
      MATERIALS AND METHODS: The effect of pinostrobin on human umbilical vein
      endothelial cells after 1 hour and after 48 hours of treatment was tested. A dose
      and time-dependent antiproliferative effect of pinostrobin was observed.
      RESULTS: After 1 hour of treatment, no significant differences between the
      control group and the cells treated with pinostrobin could be detected. After 48
      h of pinostrobin treatment, the number of cells decreased significantly. Higher
      doses had stronger inhibitory effects on the proliferation. Furthermore, we
      tested the change of membrane potential on cells that were treated with different
      concentrations of pinostrobin. We could show that the change of membrane
      potential was also time- as well as dose-dependent. CONCLUSIONS: Our hypothesis
      is that pinostrobin leads to depolarisation of the cell potential of endothelial
      cells. Since the membrane potential remains less negative, this could lead to
      instability of the membrane, resulting in cell death.

PMID- 23543452
TI  - Endovascular treatment of carotid injury.
AB  - This is a systematic review of the International Literature regarding the role of
      endovascular treatment in cases of carotid injury. Injury to the carotid artery
      is not very common but is a serious consequence associated with either blunt or
      penetrating cervical trauma. They are difficult to evaluate due to associated
      injuries. The frequent coexistence of traumatic brain injuries seems to obscure
      its presentation and concurrent systemic injuries make the management somewhat
      challenging from the perspective of both diagnosis and treatment. Although
      bleeding is a serious and potentially fatal complication of these injuries, the
      main concern should be the impairment of cerebral blood supply. In the modern era
      of increasing usage of minimally invasive treatment options and technological
      advances, endovascular approach seems to gain acceptance as a sufficient
      alternative treatment modality in carefully selected groups of these trauma
      population. Interesting issues facing this emerging technology include the
      adequate definition of the types of injuries ideally indicated for endovascular
      treatment. Those traumatic carotid lesions located proximal to aortic arch or
      near the skull base are particularly hazardous to approach and difficult to
      repair surgically and may benefit of an endovascular approach. Specifically,
      iatrogenic injuries of carotid vessels are often occur in patients with
      significant comorbidities that make their management challenging.

PMID- 23543453
TI  - A novel echocardiographic method as an indicator of endothelial dysfunction in
      patients with coronary slow flow.
AB  - BACKGROUND: To improve clinical outcomes, noninvasive imaging modalities have
      been proposed to measure and monitor atherosclerosis. Endothelial dysfunction is
      considered the first stage in the development of atherosclerosis. Brachial artery
      flow-mediated dilatation (FMD) has been impaired in patients with coronary slow
      flow (CSF). Recently, color M-mode derived propagation velocity of descending
      thoracic aorta (aortic propagation velocity-AVP) was shown to be an
      ultrasonographic marker for atherosclerosis. AIM: To assess endothelial function
      in patients with CSF and the correlation of AVP with FMD. MATERIALS AND METHODS:
      FMD and AVP were measured in 90 patients with CSF and 39 patients having normal
      coronary arteries (NCA) detected by coronary angiography. RESULTS: Compared to
      patients with normal coronary arteries patients having CSF had significantly
      lower AVP (39.1+/-8.4 vs. 53.7+/-12.7 cm/s, p < 0.001) and FMD (5.6+/-3.2 vs.
      17.6+/-4.4 %, p < 0.001) measurements. There were significant correlations
      between AVP and FMD (r = 0.524, p < 0.001). CONCLUSIONS: Transthoracic
      echocardiographic determination of color M-mode propagation velocity of
      descending aorta is a simple practical method and correlates well with coronary
      slow flow and brachial endothelial function.

PMID- 23543454
TI  - Relationship between hypoplastic right coronary artery and coronary artery
      anomalies.
AB  - OBJECTIVES: The frequency of hypoplastic right coronary artery (HRCA) and its
      contribution to coronary artery anomalies (CAAs) has not been thoroughly studied.
      Here we aimed to investigate whether a casual relationship exists between the
      presence of HRCA and CAAs. MATERIALS AND METHODS: We retrospectively reviewed
      coronary angiography records of 7500 patients. The images were carefully assessed
      for coronary artery (CA) anatomy and CAAs. Overall, we compared CAAs at the
      presence and absence of HRCA and evaluated potential association between HRCA and
      CAAs. Besides, we grouped HRCA patients according to the presence of CA disease
      (CAD) into two groups and compared their CAAs. RESULTS: While the percentage of
      HRCA was 6.2%, it was 3.34% for CAAs. The percentage of CA with anomalous origin
      (CAAO) at the presence of HRCA was significantly higher than the presence of
      normal right coronary artery (NRCA) (p < 0.01). Similarly, the percentage of
      absent left main coronary artery (ALMCA) was also considerable increased in HRCA
      patients with respect to the patients with NRCA (p < 0.01). The percentage of
      CAAO was notably higher in the CAD (-) than CAD (+) patients with HRCA (p <
      0.01). Likewise, the prevalence of ALMCA was also noticeably higher in the CAD (
      ) than CAD (+) patients with HRCA (p < 0.01). CONCLUSIONS: HRCA is a clinically
      significant and frequently encountered congenital variation. The present
      observations indicate that the presence of HRCA is closely associated with a high
      prevalence of CAAO, particularly with increased rate of ALMCA.

PMID- 23543455
TI  - Clinical feature analysis of fatal pulmonary thromboembolism: experiences from 41
      autopsy-confirmed cases.
AB  - AIM: Due to non-specific symptoms and imaging features, a timely and accurate
      diagnosis of pulmonary thromboembolism (PTE) is often difficult. This study aims
      to evaluate the frequency of, and risk factors for, autopsy-confirmed cases with
      fatal pulmonary thromboembolism (FPE) that were missed or misdiagnosed before
      death. MATERIAL AND METHODS: Forensic autopsies that were performed at the Center
      of Forensic Medicine in West China were retrospectively reviewed, and demographic
      and clinical data of autopsy-confirmed cases with FPE were collected. RESULTS:
      There were 41 cases with pathologically confirmed FPE, which represents 7.3%
      (41/558) of autopsy cases that documented sudden death in hospital. Of those 41
      cases, only 14.6% (6/41) were correctly diagnosed before death, and 85.4% (35/41)
      were missed or misdiagnosed. According to medical records, bowel movements and
      out-of-bed activity were the major triggers of FPE death, and 90% of cases had at
      least two of the known risk factors for PTE. Increasing age, orthopedic surgery,
      and multiple traumas were the most common risk factors. Additionally, of the 41
      cases with FPE, 51.2% (21/41) died in the Orthopedic Department. CONCLUSIONS: FPE
      was common in older patients who had a recent history of surgery and multiple
      traumas. Increasing the early diagnosis of PTE in high-risk patients may be
      useful for reducing the incidence of FPE.

PMID- 23543456
TI  - Mean platelet volume may be related to the degree of coronary collateral
      circulation.

PMID- 23543458
TI  - Retractions. Mizutani A, Okajima K, Uchiba M, Noguchi T. Activated protein C
      reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte
      activation. Blood. 2000;95(12):3781-3787 and Mizutani A, Okajima K, Uchiba M,
      Isobe H, Harada N, Mizutani S, Noguchi T. Antithrombin reduces
      ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte
      activation through promotion of prostacyclin production. Blood. 2003;101(8):3029
      3036.
AB  - The Editors wish to retract the 15 June 2000 and 15 April 2003 (prepublished 12
      December 2002) articles cited above. The retractions were prepublished in First
      Edition on 29 March 2013. The institutional investigations by the Oita University
      and the Nagoya Municipal University in Japan, which focused on the research of
      Kenji Okajima and Akio Mizutani, concluded that the data presented in the Blood
      2000 paper were obtained using fraudulent methods and hence cannot be considered
      reliable. Specifically, Figure 3B and Figure 3D are duplicated and rotated images
      of the same stained slide. In addition, some of the data were reused, without
      attribution, between the 2000 and 2003 Blood papers. Figure 1A-B and Figure 4A in
      both papers show identical data through 24 hours. The same applies to Figure 6A
      in the 2000 paper, Figure 7A in the 2003 paper, Figure 7A-C in the 2000 paper,
      and Figure 8A-C in the 2003 paper. The figure legends and Methods in the 2003
      paper do not indicate that these data were in part previously published. In
      addition to the issue of potential data re-use without attribution, the journal
      found possible problems with the data itself, because the figures up through 24
      hours are identical, yet purported to result from experiments 3 years apart,
      consisting of different group sizes for the sham and R/I saline groups between
      the 2 papers. Dr Uchiba agreed to the retractions. Dr Okajima was contacted by
      Blood, but did not respond. The remaining authors could not be contacted.

PMID- 23543457
TI  - Genomic instability may originate from imatinib-refractory chronic myeloid
      leukemia stem cells.
AB  - Genomic instability is a hallmark of chronic myeloid leukemia in chronic phase
      (CML-CP) resulting in BCR-ABL1 mutations encoding resistance to tyrosine kinase
      inhibitors (TKIs) and/or additional chromosomal aberrations leading to disease
      relapse and/or malignant progression. TKI-naive and TKI-treated leukemia stem
      cells (LSCs) and leukemia progenitor cells (LPCs) accumulate high levels of
      reactive oxygen species (ROS) and oxidative DNA damage. To determine the role of
      TKI-refractory LSCs in genomic instability, we used a murine model of CML-CP
      where ROS-induced oxidative DNA damage was elevated in LSCs, including quiescent
      LSCs, but not in LPCs. ROS-induced oxidative DNA damage in LSCs caused clinically
      relevant genomic instability in CML-CP-like mice, such as TKI-resistant BCR-ABL1
      mutations (E255K, T315I, H396P), deletions in Ikzf1 and Trp53, and additions in
      Zfp423 and Idh1. Despite inhibition of BCR-ABL1 kinase, imatinib did not
      downregulate ROS and oxidative DNA damage in TKI-refractory LSCs to the levels
      detected in normal cells, and CML-CP-like mice treated with imatinib continued to
      accumulate clinically relevant genetic aberrations. Inhibition of class I p21
      activated protein kinases by IPA3 downregulated ROS in TKI-naive and TKI-treated
      LSCs. Altogether, we postulate that genomic instability may originate in the most
      primitive TKI-refractory LSCs in TKI-naive and TKI-treated patients.

PMID- 23543459
TI  - Ovarian carcinoma or abdominal tuberculosis?-A diagnostic dilemma: study of
      fifteen cases.
AB  - OBJECTIVE: To evaluate the clinical, laboratory, and diagnostic features in women
      with abdominal tuberculosis that resembled advanced ovarian malignancy. METHODS:
      A retrospective review of women with abdominal tuberculosis who were managed at
      GCRI Ahmedabad from 1996 to 2001 was undertaken. RESULTS: Fifteen patients (3.06
      %) with suspected ovarian cancer cases, finally diagnosed as abdominal
      tuberculosis over a 6-year period (1996-2001), are analyzed. During this period,
      492 patients were operated for suspected ovarian malignancy. Pre-operatively,
      ultrasound-guided biopsies were inconclusive in 14 cases and hence, exploratory
      laparotomy was planned. They underwent laparotomy and biopsy for final diagnosis.
      Frozen sections-of peritoneal/omental biopsies in 11 cases and ovarian tumour in
      three cases-were indicative of tuberculosis in all the 14 cases. CONCLUSION: The
      data of this study indicate that the majority of the cases with peritoneal
      tuberculosis can be diagnosed intra-operatively through the use of frozen section
      in conjunction with clinical features. Ascites and high levels of Ca125 do not
      necessarily indicate that the clinical picture is malignant in reproductive
      women. Laparoscopic tissue biopsy may be a fundamental tool in the management of
      such cases to avoid extended surgery.

PMID- 23543460
TI  - Radioiodide induces apoptosis in human thyroid tissue in culture.
AB  - Radioiodide ((131)I) is routinely used for the treatment of toxic adenoma,
      Graves' disease, and for ablation of thyroid remnant after thyroidectomy in
      patients with thyroid cancer. The toxic effects of ionizing radiations on living
      cells can be mediated by a necrotic and/or apoptotic process. The involvement of
      apoptosis in radiation-induced cell death in the thyrocytes has been questioned.
      The knowledge of the mechanisms that underlie the thyrocyte death in response to
      radiations can help to achieve a successful treatment with the lowest (131)I
      dose. We developed a method to study the effects of (131)I in human thyroid
      tissue in culture, by which we demonstrated that (131)I induces thyroid cell
      apoptosis. Human thyroid tissues of about 1 mm(3) were cultured in vitro and cell
      viability was determined up to 3 weeks by the MTT assay. Radioiodide added to the
      culture medium was actively taken up by the tissues. The occurrence of apoptosis
      in the thyrocytes was assessed by measuring the production of a caspase-cleavage
      fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay. Neither
      variation of cell number nor spontaneous apoptosis was revealed after 1 week of
      culture. (131)I added to the culture medium induced a dose-dependent and a time
      dependent generation of M30 fragment. The apoptotic process was confirmed by the
      generation of caspase-3 and PARP cleavage products. These results demonstrate
      that (131)I induces apoptosis in human thyrocytes. Human thyroid tissue cultures
      may be useful to investigate the cell death pathways induced by (131)I.

PMID- 23543461
TI  - Kinesin KIFC1 actively transports bare double-stranded DNA.
AB  - During the past years, exogenous DNA molecules have been used in gene and
      molecular therapy. At present, it is not known how these DNA molecules reach the
      cell nucleus. We used an in cell single-molecule approach to observe the motion
      of exogenous short DNA molecules in the cytoplasm of eukaryotic cells. Our
      observations suggest an active transport of the DNA along the cytoskeleton
      filaments. We used an in vitro motility assay, in which the motion of single-DNA
      molecules along cytoskeleton filaments in cell extracts is monitored; we
      demonstrate that microtubule-associated motors are involved in this transport.
      Precipitation of DNA-bound proteins and mass spectrometry analyses reveal the
      preferential binding of the kinesin KIFC1 on DNA. Cell extract depletion of
      kinesin KIFC1 significantly decreases DNA motion, confirming the active
      implication of this molecular motor in the intracellular DNA transport.

PMID- 23543462
TI  - An evaluation of two conducted electrical weapons and two probe designs using a
      swine comparative cardiac safety model.
AB  - Despite human laboratory and field studies that have demonstrated a reasonable
      safety profile for TASER brand conducted electrical weapons (CEW), the results of
      some swine studies and arrest related deaths temporal to the use of the CEWs
      continue to raise questions regarding cardiac safety. TASER International, Inc.,
      has released a new CEW, the TASER X2, touted to have a better safety profile than
      its long-standing predecessor, the TASER X26. We have developed a model to assess
      the relative cardiac safety of CEWs and used it to compare the TASER X2 and the
      TASER X26. This safety model was also used to assess the relative safety of an
      experimental probe design as compared to the standard steel probe. Our results
      suggest that the TASER X2 has an improved safety margin over the TASER X26. The
      new probe design also has promise for enhanced cardiac safety, although may have
      some disadvantages when compared to the existing design which would make field
      use impractical. 

PMID- 23543464
TI  - Different conditions and strategies to utilize forensic radiology in the cities
      of Melbourne, Australia and Berlin, Germany.
AB  - Forensic radiology has become a common modality in many forensic practices around
      the world. Here, we report and compare the usage patterns in the cities of
      Melbourne, Australia, and Berlin, Germany, using 16 multislice scanners in two
      large forensic facilities with both machines integrated in the mortuary. While in
      Melbourne all bodies receive a full body computed tomography (CT) scan resulting
      in nearly 5,000 scans per year, the situation differs in Berlin where
      approximately 250 state prosecutor sanctioned cases are scanned per year. While
      in Melbourne the CT scanner is an integral element of the process of determining
      whether further examinations will follow, in contrast in Berlin all cases proceed
      to autopsy irrespective of the findings from the CT scan. While pathologists in
      Berlin receive on site training to use the CT scanner by a highly experienced
      forensic pathologist who has previously been involved in the Virtopsy((r))
      program in Switzerland, training of pathologists in Melbourne is multifaceted. A
      radiologist with extensive experience in the forensic environment is employed
      part time at the institute in Melbourne and provides radiology lectures including
      topics such as postmortem artifacts, regional anatomy, and neuroradiology. CT is
      gaining acceptance as a useful modality for presenting information to the courts
      and juries, as well as providing an easily accessible platform to review cases
      and initiated research projects. 

PMID- 23543463
TI  - Effects of a TASER(r) conducted energy weapon on the circulating red-blood-cell
      population and other factors in Sus scrofa.
AB  - In previous studies hematocrit has been consistently increased in an anesthetized
      animal model after exposures to TASER((r)) conducted energy weapons (CEWs). In
      the present study we analyzed changes in blood cell counts and red blood cell
      membrane proteins following two 30-s applications of a TASER C2 device (which is
      designed for civilian use). Hematocrit increased significantly from 33.2 +/- 2.4
      (mean +/- SD) to 42.8 +/- 4.6 % immediately after CEW exposure of eleven pigs
      (Sus scrofa). Red blood cell count increased significantly from 6.10 +/- 0.55 *
      10(12)/L to 7.45 +/- 0.94 * 10(12)/L, and mean corpuscular volume increased
      significantly from 54.5 +/- 2.4 fl to 57.8 +/- 2.6 fl. Mean corpuscular
      hemoglobin concentration decreased significantly from 20.5 +/- 0.7 to 18.5 +/-
      0.6 mM. Thirty protein spots (from two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, selected for detailed comparison) exhibited
      greater densities 30-min post-exposure compared with pre-exposure values. A
      greater number of echinocytes were observed following CEW exposure. On the basis
      of these results it appears that, during the strong muscle contractions produced
      by TASER CEWs, a specific population of red blood cells (RBCs) may be released
      from the spleen or other reservoirs within the body. The total time of CEW
      exposure in the present study was relatively long compared with exposures in
      common law-enforcement scenarios. Despite statistically significant changes in
      red blood cell counts (and other measures directly related to RBCs), the
      alterations were short-lived. The transient nature of the changes would be likely
      to counteract any potentially detrimental effects.

PMID- 23543465
TI  - The Hip Sports Activity Scale (HSAS) for patients with femoroacetabular
      impingement.
AB  - PURPOSE: To develop and validate a sports activity scale for patients with a
      diagnosis of femoroacetabular impingement (FAI).? METHODS: A nine level Hip
      Sports Activity Scale (HSAS) was constructed both in German and English
      languages. Fifty-nine consecutive patients undergoing surgical treatment for FAI
      at two centers in Switzerland and in the US completed a questionnaire set
      consisting of the HSAS, the University of California at Los Angeles (UCLA)
      activity scale and different hip joint-specific and generic outcome tools. For
      reliability assessment, the HSAS was completed twice about nine days apart.
      Evidence of reliability, validity and responsiveness was investigated by
      classical psychometric analyses.? RESULTS: Reliability was excellent for both the
      German and the English versions with intraclass correlation coefficients of 0.94
      and 0.96, respectively. Evidence of convergent validity was supported by moderate
      to high correlations with the UCLA activity scale and with the joint-specific
      measures used. Evidence of divergent validity was supported by low correlations
      with the SF-12 Mental Component Scale and the WOMAC stiffness subscale. The
      standardised response mean was 0.69.? CONCLUSIONS: The HSAS is a reliable and
      valid tool to determine sports levels in patients suffering from FAI. Its use in
      future studies investigating outcomes in young patients with hip disease can be
      recommended.? LEVEL OF EVIDENCE: Level III, Diagnostic Studies - An independent,
      masked comparison with an appropriate population of patients, but reference
      standard not applied to all study patients.

PMID- 23543467
TI  - Endoscopic iliotibial band release in snapping hip.
AB  - Several open surgical techniques have been used to treat recalcitrant cases of
      snapping iliotibial band with varying results. Recently, endoscopic techniques
      have become available. The purpose of this study was to investigate the results
      of a modified endoscopic iliotibial band release using a longitudinal
      retrospective case series.? Fifteen patients (three men and 12 women) with
      symptomatic external snapping hip were treated with an endoscopic release of the
      iliotibial band. The average age was 25 years (range 16-37 years). The procedure
      was performed in the lateral decubitus position using two portals; the iliotibial
      band was transversally released using a radiofrequency hook probe. The mean
      follow-up period was 33.8 months (range 12-84 months).? The snapping phenomenon
      was overcome in all the patients. The mean pre-op pain VAS score was 5.5 mm
      (range 5-7 mm) and the mean post-op pain VAS score was 0.53 mm (range 0-2 mm)
      with a statistically significant reduction with respect to the preoperative value
      (p<0.0001); sixty percent of the patients were pain-free. The mean postoperative
      Harris Hip Score was 97.5 (range 94-100). No revision procedures were indicated
      and all the patients returned to their previous level of activity. The mean
      patient satisfaction score was, on average, 9.3 mm (range 8-10 mm) on the VAS
      scale. No complications occurred.? Endoscopic iliotibial band release is a safe
      and reproducible technique with excellent results in terms of snapping phenomenon
      resolution, patient satisfaction, and return to previous level of activity. After
      strenuous sporting activities 40% of patients complained of very slight pain.

PMID- 23543466
TI  - Are crutches required after hip arthroscopy? A case-control study.
AB  - Hip arthroscopy provides a less invasive alternative to arthrotomy and has the
      potential for more rapid rehabilitation. Few guidelines exist for rehabilitation
      after hip arthroscopic surgery. However, these are not corroborated with evidence
      of objective outcome measures. In particular, the period for which crutches
      should be used is imprecisely explained, if explained at all. The purpose of this
      study was to determine whether or not crutch use is required after hip
      arthroscopic surgery, and if so, for how long.? We compare a postoperative
      regimen of four weeks partial weight bearing on crutches (Group 1, n = 85) with a
      regimen that permitted patients to fully weight bear immediately after surgery if
      comfort allowed (Group 2, n = 80). We used the modified Harris hip score (mHHS)
      as an outcome measure at six weeks and six months after surgery. For Group 1, the
      mean duration of crutch use was 28.2 days and the mean postoperative mHHS at six
      weeks and six months showed significant improvement compared with preoperatively.
      For Group 2 the mean duration of crutch use was 13.4 days and the mean
      postoperative mHHS at six weeks and six months also showed significant
      improvement compared with preoperatively. The results demonstrated no significant
      difference in postoperative mHHS between the two groups at six weeks and six
      months after surgery.? There thus appears to be no need to enforce a defined
      period of partial weight bearing on crutches after hip arthroscopic surgery,
      irrespective of the procedure undertaken.

PMID- 23543468
TI  - How far above the true anatomic position can the acetabular cup be placed in
      total hip arthroplasty?
AB  - INTRODUCTION: There is controversy about which is more suitable for determining
      correct socket position in patients with severe bone deficiency of the acetabular
      roof because of developmental dysplasia of the hip (DDH): the anatomic centre of
      hip rotation or a high centre. ? METHOD: We evaluated the relationship, in 200
      hips, between the centre of rotation and presence of the Trendelenburg sign to
      determine the upper limit of cup position from the standpoint of hip-abductor
      strength. ? RESULTS: Of the 200 hips, 20 (10%) showed a positive Trendelenburg
      sign. There were no statistically significant differences between parameters (the
      centre of rotation, femoral offset, abductor lever arm) regarding the presence of
      the Trendelenburg sign except for age at surgery. Patients with a positive
      Trendelenburg sign were significantly older (64.1 +/- 9.4 years) than those with
      a negative Trendelenburg sign (58.8 +/- 7.7 years) (P = 0.01).? CONCLUSIONS: Our
      findings indicate that a high centre of hip rotation of up to approximately 30 mm
      from the inter-teardrop line is a feasible option for patients with DDH from the
      standpoint of hip-abductor strength if stems are used that allow the restoration
      of femoral offset and the abductor lever arm.

PMID- 23543469
TI  - Posterior wall reconstruction using intertrochanteric crest strut graft in
      comminuted posterior acetabular wall fractures.
AB  - Posterior wall fractures are the most common acetabular fractures. Despite being
      frequently the easiest to treat, posterior acetabular wall reconstruction
      following such injuries can be challenging. A prospective study was conducted to
      evaluate the efficacy of a new surgical technique using gluteus medius muscle
      pedicled intertrochanteric crest graft for the reconstruction of comminuted
      posterior acetabular wall fractures where primary comminuted fragments were
      beyond fixation. This technique has been performed on six patients from 2010 to
      2012. The radiologic (Matta score) and clinical evaluation (modified Merle
      d'Aubigne and Postel score) were recorded at their final follow-up. ?The mean
      follow-up was 15.2 months. The radiological outcome by plain radiographs was
      graded as anatomical in all six patients, the clinical outcome by modified Merle
      d'Aubigne and Postel score was considered to be excellent in two patients, good
      in four. ?Reconstruction of the posterior acetabular wall using gluteus medius
      muscle-pedicled intertrochanteric crest graft may be appropriate in some
      instances. The early radiological and clinical results of this new technique were
      promising.

PMID- 23543470
TI  - Learning curve analysis of the Collum Femoris Preserving total hip surgical
      technique.
AB  - The aim of this study was to determine whether femoral neck preserving total hip
      arthroplasty would become less difficult and more efficient during the first 20
      cases and to identify potential pitfalls during the introduction of this
      procedure. The difficulty and efficiency of the initial 20 procedures performed
      by four surgeons was prospectively determined by analysing a total of 68 video
      recordings using time-action analysis. This method measures the duration and
      efficiency of individual actions needed for a surgeon to achieve his or her goal.
      Afterwards, we reviewed all actions with a long duration and discussed possible
      causes of delay with the surgeons to identify possible pitfalls. We found a
      decrease of difficulty and an increase of efficiency during the first 20 cases
      and a more consistent execution after the initial five cases. Estimating the
      correct osteotomy level and stem curvature was often difficult, which resulted in
      a variable stem position. Radiologic analysis demonstrated a tendency for varus
      position and increased leg length throughout the series, even after the surgeons
      demonstrated technical proficiency.

PMID- 23543471
TI  - The Basis CL cemented femoral stem: results after 8.9 years follow-up.
AB  - This prospective study was conducted to demonstrate that the matte-finish Basis
      CL cemented endoprosthetic stem delivers good qualitative results after 10 years.
      Between January and December 1999, 205 consecutive hips (201 patients; 74.5 +/-
      6.8 years at surgery) underwent primary total hip arthroplasty with the Basis CL
      and the same acetabular cup (RM Classic cup) at a single institution. Follow-up
      data at 10 years was available for 120 hips (average follow-up of 8.9 years, +/
      2.9). Mean Harris Hip Score improved from 39.5 +/- 16.8 at baseline to 75.9 +/-
      16.7 at 10-year follow-up (p<0.001). Four hips required revision during the
      study: three for infection and one for pain. There were no cases of aseptic
      loosening, implant migration, or stem fracture. Cumulative survival at 10 years
      was 97.4% with the endpoint of revision for any reason. In conclusion, results
      with the matte-finish cemented Basis CL indicated that it was safe and effective
      after medium-term follow-up.

PMID- 23543472
TI  - Fractures of the greater trochanter following total hip replacement.
AB  - We studied the incidence of greater trochanteric fractures at our department
      following THR. In all we examined 911 patients retrospectively and found the
      occurance of a greater trochanteric fracture to be 3%. Patients with fractures
      had significantly poorer outcome on Oxford Hip score, Pain VAS, Satisfaction VAS
      and EQ-5D compared to THR without fractures. Greater trochanteric fracture
      following THR is one of the most common complications following THR. It has
      previously been thought to have little impact on the overall outcome following
      THR, but our study suggests otherwise.

PMID- 23543473
TI  - Evaluation of preoperative hip range of motion under general anaesthesia.
AB  - Hip range of motion (ROM) may be an important preoperative variable, however,
      measurement of hip ROM can be affected by various factors. The purposes of this
      study were to compare conventional preoperative ROM measurements with those
      measurements obtained under general anaesthesia, and to better define the
      associations between preoperative hip ROM, and demographic, functional, and
      diagnostic variables.?Conventional preoperative hip ROM and ROM under general
      anaesthesia were prospectively measured in 471 hips. Harris pain score, the Crowe
      classification, and the diagnosis were also investigated. ?The hip ROM in all
      directions under general anaesthesia was significantly greater than conventional
      preoperative hip ROM. There were correlations between conventional preoperative
      hip ROM and the Harris hip pain score. Hip ROM with Crowe type I deformity under
      anaesthesia was significantly greater than in hips with type II, III or IV. ROM
      under anaesthesia of osteonecrosis hips was significantly greater than
      osteoarthritis and dislocated hips. Conventional preoperative ROM in men was
      greater in flexion and external rotation compared to women. Internal rotation
      motion in women in both conventional preoperative ROM and ROM under anaesthesia
      was greater than in men. ?Hip pain, Crowe classification and diagnosis could
      influence preoperative hip ROM. Measurement of hip ROM under general anaesthesia
      could better reflect true ROM compared to measurement without anaesthesia.

PMID- 23543474
TI  - Revision hip replacement in patients 55 years of age and younger.
AB  - The purpose of this study was to assess the efficacy and complications associated
      with revision hip arthroplasty undertaken in patients under 55 years of age. A
      review of our revision hip database showed that 430 revision hip arthroplasties
      undertaken over the past 9 years had a minimum follow-up of 2 years. Of these, 84
      (46 female, 38 male) patients were under 55 years of age. The index procedures
      were preformed at an average age of 46 years (range 15 years to 54 years). The
      etiology of failure was aseptic loosening (74%), followed by infection (8%) and
      recurrent dislocation (7%). In the majority of cases, uncemented implants were
      used at revision surgery (91% uncemented femoral stem, 100% uncemented acetabular
      cup). A form of bone graft was necessary in 39% of cases. At final follow-up
      satisfactory progress was noted in all cases with a statistically significant
      improvement in Harris hip score (p<0.05). Revision of hip arthroplasty in
      patients below 55 years of age is associated with significant improvement in
      function and patient satisfaction.

PMID- 23543475
TI  - The effect of treadmill running on passive avoidance learning in animal model of
      Alzheimer disease.
AB  - BACKGROUND: Alzheimer's disease was known as a progressive neurodegenerative
      disorder in the elderly and is characterized by dementia and severe neuronal loss
      in the some regions of brain such as nucleus basalis magnocellularis. It plays an
      important role in the brain functions such as learning and memory. Loss of
      cholinergic neurons of nucleus basalis magnocellularis by ibotenic acid can
      commonly be regarded as a suitable model of Alzheimer's disease. Previous studies
      reported that exercise training may slow down the onset and progression of memory
      deficit in neurodegenerative disorders. This research investigates the effects of
      treadmill running on acquisition and retention time of passive avoidance deficits
      induced by ibotenic acid nucleus basalis magnocellularis lesion. METHODS: MALE
      WISTAR RATS WERE RANDOMLY SELECTED AND DIVIDED INTO FIVE GROUPS AS FOLLOWS:
      Control, sham, Alzheimer, exercise before Alzheimer, and exercise groups.
      Treadmill running had a 21 day period and Alzheimer was induced by 5 MUg/MUl
      bilateral injection of ibotenic acid in nucleus basalis magnocellularis. RESULTS:
      Our results showed that ibotenic acid lesions significantly impaired passive
      avoidance acquisition (P < 0.01) and retention (P < 0.001) performance, while
      treadmill running exercise significantly (P < 0.001) improved passive avoidance
      learning in NBM-lesion rats. CONCLUSION: Treadmill running has a potential role
      in the prevention of learning and memory impairments in NBM-lesion rats.

PMID- 23543476
TI  - Structural and mechanistic insights into the electron flow through protein for
      cytochrome c-tethering copper nitrite reductase.
AB  - Copper-containing nitrite reductases (CuNiRs), which catalyse the reversible one
      electron reduction of nitrite to nitric oxide, are members of a large family of
      multi-copper enzymes that require an interprotein electron transfer (ET) reaction
      with redox partner proteins. Here, we show that the naturally fused type of CuNiR
      tethering a cytochrome c (Cyt c) at the C-terminus folds as a unique trimeric
      domain-swapped structure and has a self-sufficient electron flow system. The C
      terminal Cyt c domain is located at the surface of the type 1 copper (T1Cu) site
      in the N-terminal CuNiR domain from the adjacent subunit, the heme-to-Cu distance
      (10.6 A) of which is comparable to the transient ET complex of normal CuNiR with
      Cyt c. The structural aspects for the domain-domain interface and the ET kinetics
      indicate that the Cyt c-CuNiR domain interaction should be highly transient. The
      further electrochemical analysis of the interprotein ET reaction with a cognate
      redox partner protein suggested that an electron is directly transferred from the
      partner to the T1Cu. Structural and mechanistic comparisons of Cyt c-CuNiR with
      another cupredoxin-tethering CuNiR highlight the behaviours of extra domains on
      the fusion types of CuNiRs required for ET through proteins. 

PMID- 23543477
TI  - Interaction between NADH and electron-transferring flavoprotein from Megasphaera
      elsdenii.
AB  - Electron-transferring flavoprotein (ETF) from the anaerobic bacterium Megasphaera
      elsdenii is a heterodimer containing two FAD cofactors. Isolated ETF contains
      only one FAD molecule, FAD-1, because the other, FAD-2, is lost during
      purification. FAD-2 is recovered by adding FAD to the isolated ETF. The two FAD
      molecules in holoETF were characterized using NADH. Spectrophotometric titration
      of isolated ETF with NADH showed a two-electron reduction of FAD-1 according to a
      monophasic profile indicating that FAD-1 receives electrons from NADH without
      involvement of FAD-2. When holoETF was titrated with NADH, FAD-2 was reduced to
      an anionic semiquinone and then was fully reduced before the reduction of FAD-1.
      The midpoint potential values at pH 7 were +81, -136 and -279 mV for the
      reduction of oxidized FAD-2 to semiquinone, semiquinone to the fully reduced FAD
      2 and the two-electron reduction of FAD-1, respectively. Both FAD-1 and FAD-2 in
      holoETF were reduced by excess NADH very rapidly. The reduction of FAD-2 was
      slowed by replacement of FAD-1 with 8-cyano-FAD indicating that FAD-2 receives
      electrons from FAD-1 but not from NADH directly. The present results suggest that
      FAD-2 is the counterpart of the FAD in human ETF, which contains one FAD and one
      AMP.

PMID- 23543478
TI  - Gravin gene expression in acute myeloid leukemia.
AB  - Acute leukemias are caused by genetic and epigenetic mechanisms involving tumor
      suppressor genes and oncogenes. Aberrant DNA methylation patterns are the most
      frequent molecular alterations detected in acute myeloid leukemia (AML). Gravin
      is down-regulated in several solid tumors and is implicated in tumorigenesis. To
      explore its role in the molecular pathogenesis and its possible prognostic
      importance in AML, we have evaluated the expression levels of the gravin gene in
      83 acute myeloid leukemia patients as compared with controls using quantitative
      real-time polymerase chain reaction (qRT-PCR). Mean gravin expression was 0.53 +/
      1.34 and 8.81 +/- 11.6 for patients and controls, respectively, and was found to
      be about 16-fold lower than controls. Gravin gene expression was lower than
      controls in 83.1 % (69/83) and was similar to controls in 16.9 % (14/83) of cases
      (p < 0.0001). It was found that there was no significant correlation between
      gravin expression and laboratory prognostic markers (p > 0.05). Gravin expression
      was highest in complete remission (1.065 +/- 1.79) and lowest in relapse (0.019
      +/- 0.03) with a statistical difference (p = 0.004). Patients with gravin
      expression below median level had higher risk to develop relapse (OR = 8.689, 95
      % CI = 2.464-30.638; p < 0.0001). No statistical correlation was reported between
      gravin expression and survival times (OS, DFS) (p = 0.482, 0.409, respectively),
      and this was confirmed in multivariate analysis. Gravin gene expression was found
      to be decreased in acute myeloid leukemia, and the degree of its decreased
      expression has been found to be correlated with poor prognosis.

PMID- 23543479
TI  - The pathogenesis of diabetic nephropathy: focus on microRNAs and proteomics.
AB  - The prevalence of type 2 diabetes mellitus is growing exponentially in Western
      countries, and the incidence of this condition is today increasing worldwide.
      Other than for cardiovascular complications, diabetes is particularly challenging
      for the kidney's health and proper function. Prolonged exposure of the kidneys to
      hyperglycemia in fact often results in a clinical complication called diabetic
      glomerulosclerosis, also known as diabetic nephropathy. Diabetic nephropathy
      represents today the leading cause of end-stage renal disease in Western
      countries. When left untreated or undiagnosed, diabetic nephropathy is ultimately
      responsible for the need for dialysis and, in the worst cases, kidney
      transplantation of the affected individuals. The pathogenesis of diabetic
      nephropathy has been studied extensively. A great number of metabolites,
      cytokines, proteins and transcription factors play a role in the accumulation of
      extracellular matrix and mesangial proliferation in the glomerulus; importantly,
      these phenotypic alterations are considered the 2 histological hallmarks of
      diabetic nephropathy. Additional effort is however required to understand the
      wide network of biochemical pathways that link diabetes to the renal damage in
      the long run. The integrative analysis of the proteomic and transcriptomic
      features of body fluids and/or bioptic samples among different categories of
      patients affected by diabetic nephropathy, if based on the accurate
      classification of the histopathological changes in the glomerular and
      tubulointerstitial compartment, could lead to the identification of new early
      biomarkers. This approach could represent an effective, noninvasive, alternative
      tool for early diagnosis and intervention. 

PMID- 23543480
TI  - Effects of prednisone on biomarkers of tubular damage induced by radiocontrast in
      interventional cardiology.
AB  - BACKGROUND: Contrast-induced nephropathy (CI-AKI) is a complication of
      diagnostic/therapeutic hemodynamic procedures in cardiology, which may also cause
      renal cholesterolinic atheroembolism. Despite the ?severe clinical impact of
      these complications, there is no optimal therapy for preventing and treating
      them. We suggest a short course of high-dose steroids as an effective preventive
      measure. METHODS: Patients at risk of CI-AKI (n = 38) undergoing cardiovascular
      procedures were assigned 1:1 to 1 of 2 experimental arms (prednisone+hydration
      vs. hydration alone). Oral prednisone 1 mg/kg was administered 12 hours before,
      at 6 am on the same day, and 24 hours following the procedure. Serum creatinine
      was tested immediately before and again 24-48 hours after the procedure;
      neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM
      1), protein and albumin were assayed in spot urine before and 6 hours after the
      procedure.? RESULTS: NGAL and KIM-1 tended to rise after the procedure, but to a
      lesser degree in the prednisone group (delta NGAL: hydration = +128%, prednisone
      = +46%; ?p = 0.26; delta KIM-1: hydration = +99%, prednisone = +11%; p = 0.02).
      Proteinuria and albuminuria decreased significantly in the prednisone group. In 5
      patients developing CI-AKI, their delta NGAL and delta KIM-1 did not differ from
      the values seen in patients without ?CI-AKI. Hypertension, peripheral
      arteriopathy and use of low-dose aspirin or diuretics were positive predictors of
      baseline NGAL, while treatment with calcium channel blockers and statins were
      negative predictors. Statins were negative predictors of baseline KIM-1.
      CONCLUSIONS: A short course of prednisone reduces the procedure-induced changes
      in biomarkers of renal tubular damage. This study suggests that steroids had a
      tubule-protecting effect.

PMID- 23543481
TI  - Phosphate binders in moderate chronic kidney disease: where do we stand?
AB  - Phosphate levels are strikingly associated with poor outcomes in chronic kidney
      disease (CKD) and end-stage renal disease (ESRD) patients. Numerous
      epidemiological studies have repeatedly documented a worrisome link between serum
      phosphorus and adverse outcome in CKD stages 3 and 4. Notably, some but not all
      series suggest that the risk is significantly increased even for serum levels
      within the reference range of normality for serum phosphorus. The use of
      phosphate binders as a tool for controlling hyperphosphatemia has also been
      associated in observational studies with a better survival both in CKD and ESRD.
      However, no randomized clinical trial (RCT) has ever tested the impact of
      phosphate-lowering interventions (i.e., phosphate binder or nutritional
      intervention) on hard outcomes. Furthermore, a recent RCT seems to caution
      against the indiscriminate use of phosphate binders in CKD patients not receiving
      maintenance dialysis. Considering the clinical sequelae associated with phosphate
      overload in CKD, phosphate-lowering therapy is perceived as crucial and safe to
      prevent chronic kidney disease-mineral bone disorder (CKD-MBD). However, when to
      start in the course of CKD, how to monitor and whether to choose a calcium-based
      or a calcium-free phosphate binder are still subject to debate. Further research
      is deemed necessary to elucidate whether early treatment with phosphate binders
      is safe and may attenuate the CKD-MBD progression through phosphate load
      reduction. 

PMID- 23543482
TI  - Automated UV-C mutagenesis of Kluyveromyces marxianus NRRL Y-1109 and selection
      for microaerophilic growth and ethanol production at elevated temperature on
      biomass sugars.
AB  - The yeast Kluyveromyces marxianus is a potential microbial catalyst for fuel
      ethanol production from a wide range of biomass substrates. To improve its growth
      and ethanol yield at elevated temperature under microaerophilic conditions, K.
      marxianus NRRL Y-1109 was irradiated with UV-C using automated protocols on a
      robotic platform for picking and spreading irradiated cultures and for processing
      the resulting plates. The plates were incubated under anaerobic conditions on
      xylose or glucose for 5 mo at 46  degrees C. Two K. marxianus mutant strains
      (designated 7-1 and 8-1) survived and were isolated from the glucose plates. Both
      mutant strains, but not wild type, grew aerobically on glucose at 47  degrees C.
      All strains grew anaerobically at 46  degrees C on glucose, galactose,
      galacturonic acid, and pectin; however, only 7-1 grew anaerobically on xylose at
      46  degrees C. Saccharomyces cerevisiae NRRL Y-2403 did not grow at 46  degrees C
      on any of these substrates. With glucose as a carbon source, ethanol yield after
      3 d at 46  degrees C was higher for 8-1 than for wild type (0.51 and 0.43 g
      ethanol/g glucose, respectively). With galacturonic acid as a carbon source, the
      ethanol yield after 7 d at 46  degrees C was higher for 7-1 than for wild type
      (0.48 and 0.34 g ethanol/g galacturonic acid, respectively). These mutant strains
      have potential application in fuel ethanol production at elevated temperature
      from sugar constituents of starch, sucrose, pectin, and cellulosic biomass. 

PMID- 23543483
TI  - Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with
      piribedil.
AB  - Apathy is one of the most common symptoms encountered in Parkinson's disease, and
      is defined as a lack of motivation accompanied by reduced goal-directed
      cognition, behaviour and emotional involvement. In a previous study we have
      described a delayed withdrawal syndrome after successful motor improvement
      related to subthalamic stimulation allowing for a major decrease in dopaminergic
      treatment. This withdrawal syndrome correlated with a diffuse mesolimbic
      dopaminergic denervation. To confirm our hypothesis of parkinsonian apathy being
      related to mesolimbic dopaminergic denervation, we performed a randomized
      controlled study using piribedil, a relatively selective D2/D3 dopamine agonist
      to treat parkinsonian apathy, using the model of postoperative apathy. A 12-week
      prospective, placebo-controlled, randomized, double-blinded trial was conducted
      in 37 patients with Parkinson's disease presenting with apathy (Starkstein Apathy
      Scale score > 14) following subthalamic nucleus stimulation. Patients received
      either piribedil up to 300 mg per day (n = 19) or placebo (n = 18) for 12 weeks.
      The primary end point was the improvement of apathy under treatment, as assessed
      by the reduction of the Starkstein Apathy Scale score in both treatment groups.
      Secondary end points included alleviation in depression (Beck Depression
      Inventory), anxiety (Beck Anxiety Inventory), improvement of quality of life
      (PDQ39) and anhedonia (Snaith-Hamilton Pleasure Scale). Exploratory endpoints
      consisted in changes of the Robert Inventory score and Hamilton depression
      scales. An intention to treat analysis of covariance analysis was performed to
      compare treatment effects (P < 0.05). The number of premature study dropouts was
      seven in the placebo and five in the piribedil groups, mostly related to
      intolerance to hypodopaminergic symptoms. At follow-up evaluation, the apathy
      score was reduced by 34.6% on piribedil versus 3.2% on placebo (P = 0.015). With
      piribedil, modifications in the Beck depression and anxiety scores were -19.8%
      and -22.8%, respectively versus +1.4% and -8.3% with placebo, without reaching
      significance level. Piribedil led to a trend towards improvement in quality of
      life (-16.2% versus +6.7% on placebo; P = 0.08) and anhedonia (-49% versus -5.6%
      on the placebo; P = 0.08). Apathy, assessed by the Robert Inventory score,
      improved by 46.6% on piribedil and worsened by 2.3% on placebo (P = 0.005).
      Depression, measured by the Hamilton score, improved in the piribedil group (P =
      0.05). No significant side effects were observed. The present study provides a
      class II evidence of the efficacy of the dopamine agonist piribedil in the
      treatment of apathy in Parkinson's disease.

PMID- 23543485
TI  - OPA1 loss of function affects in vitro neuronal maturation.
AB  - Mitochondrial dynamics control the organelle's morphology, with fusion leading to
      the formation of elongated tubules and fission leading to isolated puncta, as
      well as mitochondrial functions. Recent reports have shown that disruptions of
      mitochondrial dynamics contribute to neurodegenerative diseases. Mutations of the
      inner membrane GTPase OPA1 are responsible for type 1 dominant optic atrophy, by
      mechanisms not fully understood. We show here that in rodent cortical primary
      neurons, downregulation of the OPA1 protein leads to fragmented mitochondria that
      become less abundant along the dendrites. Furthermore, this inhibition results in
      reduced expression of mitochondrial respiratory complexes as well as
      mitochondrial DNA, decreased mitochondrial membrane potential, and diminished
      reactive oxygen species levels. The onset of synaptogenesis was markedly impaired
      through reductions in pre- and postsynaptic structural protein expression and
      synapse numbers without first affecting the dendritic arborization. With longer
      time in culture, OPA1 extinction led to a major restriction of dendritic growth,
      together with reduction of synaptic proteins. Furthermore, in maturing neurons we
      observed a transitory increase in mitochondrial filament length, associated with
      marked changes in the expression levels of OPA1, which occurred at the onset of
      synaptogenesis simultaneously with transitory increase in reactive oxygen species
      levels and NRF2/NFE2L2 nuclear translocation. This observation suggests that
      mitochondrial hyperfilamentation acts upstream of a reactive oxygen species
      dependent NRF2 transcriptional activity, possibly impacting neuronal maturation,
      such a process being impaired by insufficient amount of OPA1. Our findings
      suggest a new role for OPA1 in synaptic maturation and dendritic growth through
      maintenance of proper mitochondrial oxidative metabolism and distribution,
      highlighting the role of mitochondrial dynamics in neuronal functioning and
      providing insights into dominant optic atrophy pathogenesis, as OPA1 loss
      affecting neuronal maturation could lead to early synaptic dysfunction.

PMID- 23543484
TI  - Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin
      3 gene.
AB  - In 2001, we reported linkage of an autosomal dominant form of limb-girdle
      muscular dystrophy, limb-girdle muscular dystrophy 1F, to chromosome 7q32.1-32.2,
      but the identity of the mutant gene was elusive. Here, using a whole genome
      sequencing strategy, we identified the causative mutation of limb-girdle muscular
      dystrophy 1F, a heterozygous single nucleotide deletion (c.2771del) in the
      termination codon of transportin 3 (TNPO3). This gene is situated within the
      chromosomal region linked to the disease and encodes a nuclear membrane protein
      belonging to the importin beta family. TNPO3 transports serine/arginine-rich
      proteins into the nucleus, and has been identified as a key factor in the HIV
      import process into the nucleus. The mutation is predicted to generate a 15-amino
      acid extension of the C-terminus of the protein, segregates with the clinical
      phenotype, and is absent in genomic sequence databases and a set of >200 control
      alleles. In skeletal muscle of affected individuals, expression of the mutant
      messenger RNA and histological abnormalities of nuclei and TNPO3 indicate altered
      TNPO3 function. Our results demonstrate that the TNPO3 mutation is the cause of
      limb-girdle muscular dystrophy 1F, expand our knowledge of the molecular basis of
      muscular dystrophies and bolster the importance of defects of nuclear envelope
      proteins as causes of inherited myopathies.

PMID- 23543486
TI  - The clinical value of tumor FDG uptake for predicting axillary lymph node
      metastasis in breast cancer with clinically negative axillary lymph nodes.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical value of 18F
      fluorodeoxyglucose (FDG) uptake and the clinicopathological or
      immunohistochemical findings of the primary tumor to predict axillary lymph node
      (ALN) metastasis in breast cancer with clinically negative ALN. METHODS: This
      study retrospectively enrolled 104 women (49.43 +/- 9.9 years) having breast
      cancer with clinically negative ALN using all types of preoperative imaging
      modalities including ultrasonography, FDG positron emission tomography, and
      magnetic resonance imaging. All cases of breast cancer in this study were proven
      as invasive ductal carcinoma with >=1 cm in size. The final diagnosis of ALN
      status was confirmed by permanent pathology after operation. RESULTS: Among 104
      breast cancers with clinically negative ALN, 21 breast cancers (20.2 %) were
      proven to have ALN metastasis. The ROC curve analysis showed that the best cut
      off value of SUVmax for identifying ALN metastasis was 9.8 with 33.3 %
      sensitivity and 92.8 % specificity (AUC = 0.656; p = 0.027). The multivariable
      analysis revealed that primary tumors with SUVmax >9.8 (p = 0.011) and D2-40
      positivity (p = 0.027) were independently associated with ALN metastasis with
      odds ratios of 5.516 (CI 1.475-20.6333) and 3.409 (CI 1.154-10.072),
      respectively. CONCLUSION: Our study demonstrates that the incidence of ALN
      metastasis in even rigorously clinically evaluated breast cancer without
      suspiciously positive ALN is still not negligible, and while a high SUVmax of the
      primary tumor may be associated with a higher incidence of ALN metastasis in
      breast cancer with clinically negative ALN, a low SUVmax does not exclude ALN
      metastasis.

PMID- 23543489
TI  - Anomalous venous anatomy leading to malposition and unusual complication of a
      left subclavian Hickman line.

PMID- 23543490
TI  - Access of a fully rotated implantable port leads to extravasation.

PMID- 23543491
TI  - Femoro-saphenous arteriovenous access-related lower limb ischemia treated by
      distal arteries percutaneous angioplasty.
AB  - This is the first reported case of transposed femoro-saphenous angio-access
      complicated after four years by distal ischemia, which was successfully treated
      by percutaneous transluminal angioplasty (PTA) of the distal femoral and
      popliteal artery. Endovascular recanalization and angioplasty of the distal
      vessels offers a minimally invasive approach with preservation of the angio
      access in these patients with high comorbidities. 

PMID- 23543492
TI  - Early experience with a newly developed electrospun polycarbonate-urethane
      vascular graft for hemodialysis access.
AB  - PURPOSE: In this pilot study, we tested a newly developed electrospun
      multilayered, self-sealing graft, AVfloTM, specifically designed for early
      hemodialysis access. ? METHODS: Ten eligible consenting patients had a
      polycarbonate-urethane graft (AVfloTM) implanted and were followed up
      prospectively for at least six months. Performance measures included graft
      patency, complications and time to first cannulation. Mean age of the patients
      was 66.7 +/- 10 years. Chronic glomerulonephritis was the most common cause of
      renal failure. A total of 70% of the patients had a history of previous vascular
      access and 40% history of minimally invasive radiologic procedures for patency
      maintenance. In 40% of the cases the need for AV graft implantation was because
      of recurrent infections from permanent catheter for dialysis. Seven grafts were
      placed in the upper arm and three in the thigh. Mean follow up was 230 +/- 75
      days. ? RESULTS: There were no systemic or local reactions to the graft and we
      did not report any graft infections. Two grafts thrombosed because of severe
      bleeding post-cannulation due to an incorrect needle puncture. Both grafts were
      successfully thrombectomized. Primary and secondary patency rates at six months
      were 60% and 78%, respectively. These patency rates were comparable to those
      reported for other polyether-urethane and ePTFE grafts. Median time to first
      cannulation was seven days (3-21) and all puncture sites sealed in less than five
      minutes.

PMID- 23543493
TI  - Problems with using a covered stent to treat bleeding in autogenous fistulae.

PMID- 23543495
TI  - Sphingobium sufflavum sp. nov., isolated from a freshwater lake.
AB  - A Gram-stain negative, rod-shaped, non-motile, non-spore-forming and aerobic
      bacterial strain, designated HL-25(T), was isolated and characterized in a
      taxonomic study using a polyphasic approach. Comparative analysis of the 16S rRNA
      gene sequences showed that the isolate constituted a distinct branch within the
      genus Sphingobium, showing the highest level of 16S rRNA gene sequence similarity
      to Sphingobium vulgare HU1-GD12(T) (96.6 %). The major fatty acids (>10%) of
      strain HL-25(T) were C(18:1)omega7c, C(16:0), summed feature 3 (comprising
      C(16:1)omega7c and/or C(16:1)omega6c) and C(18:0). The major cellular hydroxy
      fatty acid was C(14:0) 2-OH. The major isoprenoid quinone was Q-10 and the DNA
      G+C content was 63.8 mol%. The polar lipid profile consisted of a mixture of
      sphingoglycolipid, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidyldimethylethanolamine, diphosphatidylglycerol, an uncharacterized
      glycolipid, an uncharacterized aminophospholipid and four uncharacterized
      phospholipids. The polyamine pattern of strain HL-25(T) contained spermidine and
      putrescine. On the basis of these genotypic, chemotaxonomic and phenotypic data,
      strain HL-25(T) represents a novel species in the genus Sphingobium, for which
      the name Sphingobium sufflavum sp. nov. is proposed. The type strain is HL-25(T)
      ( =BCRC 80413(T) =KCTC 23953(T)).

PMID- 23543496
TI  - Geodermatophilus normandii sp. nov., isolated from Saharan desert sand.
AB  - A novel Gram-reaction-positive actinobacterial strain, designated CF5/3(T), was
      isolated from a sand sample obtained in the Sahara Desert, Chad. The greenish
      black-pigmented isolate was aerobic and exhibited optimal growth from 25-40 
      degrees C at pH 6.0-10.0 with 0-1% (w/v) NaCl. Chemotaxonomic and molecular
      characteristics of the isolate matched those described for members of the genus
      Geodermatophilus. The DNA G+C content of the genome of the novel strain was 75.5
      mol%. The peptidoglycan contained meso-diaminopimelic acid as diagnostic diamino
      acid. The main phospholipids were diphosphatidylglycerol, phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylinositol and a minor fraction of
      phosphatidylglycerol. MK-9(H4) was the dominant menaquinone, and galactose was
      detected as a diagnostic sugar. The major cellular fatty acids were branched
      chain saturated acids: iso-C(15:0) and iso-C(16:0). Analysis of 16S rRNA gene
      sequences showed 95.6-98.8% pairwise sequence identity with the members of the
      genus Geodermatophilus. Based on phenotypic and chemotaxonomic properties, as
      well as phylogenetic distinctiveness, the isolate represents a novel species,
      Geodermatophilus normandii, with the type strain CF5/3(T) ( =DSM 45417(T) =CCUG
      62814(T) =MTCC 11412(T)).

PMID- 23543497
TI  - Brevibacterium jeotgali sp. nov., isolated from jeotgal, a traditional Korean
      fermented seafood.
AB  - A Gram-staining-positive, aerobic, non-motile bacterium, designated strain SJ5
      8(T), was isolated from seau-jeot (shrimp jeotgal), a traditional fermented
      seafood in South Korea. Cells were non-spore-forming rods showing catalase- and
      oxidase-positive reactions. Growth of strain SJ5-8(T) was observed at 10-37 
      degrees C (optimum, 30  degrees C), at pH 6.0-9.0 (optimum, pH 7.5-8.5) and in
      the presence of 0-14% (w/v) NaCl (optimum, 5%). Phylogenetic inference based on
      16S rRNA gene sequences showed that the strain formed a tight phyletic lineage
      with members of the genus Brevibacterium. Strain SJ5-8(T) was most closely
      related to Brevibacterium yomogidense MN-6-a(T), Brevibacterium daeguense 2C6
      41(T) and Brevibacterium salitolerans TRM 415(T) with similarities of 98.9, 97.5
      and 97.4%, respectively. The DNA-DNA relatedness values between strain SJ5-8(T)
      and the type strains of B. yomogidense, B. daeguense and B. salitolerans were
      51.7 +/- 1.9%, 22.2 +/- 4.0% and 52.4 +/- 3.8%, respectively. Chemotaxonomic data
      (major sole isoprenoid quinone, MK-8(H2); major diagnostic diamino acid, meso
      diaminopimelic acid; major polyamines, putrescine and cadaverine; major cellular
      fatty acids, anteiso-C(15:0), iso-C(15:0) and anteiso-C(17:0); major polar
      lipids, phosphatidylglycerol and diphosphatidylglycerol; DNA G+C content, 69.3
      mol%) also supported the affiliation of strain SJ5-8(T) to the genus
      Brevibacterium. Therefore, strain SJ5-8(T) represents a novel species of the
      genus Brevibacterium, for which the name Brevibacterium jeotgali sp. nov. is
      proposed. The type strain is SJ5-8(T) ( =KACC 16911(T) =JCM 18571(T)).

PMID- 23543498
TI  - Mongoliicoccus alkaliphilus sp. nov. and Litoribacter alkaliphilus sp. nov.,
      isolated from salt pans.
AB  - Four bacterial strains (JC165(T), JC166(T), JC169 and JC170) were isolated from
      salt pan soils from a coastal region of Tamilnadu, India. They were obligately
      aerobic, pink- to red-pigmented, mesophilic, haloalkaliphiles having
      chemoorganoheterotrophic growth on various carbon sources and were catalase- and
      oxidase-positive. Phototrophic growth and bacteriochlorophyll a were absent in
      all four strains. Major carotenoids present were beta-carotene and rhodoxanthin.
      The main fatty acid in all strains was iso-C(15:0). The main polar lipids were
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC) as well as a few
      unidentified lipids. Bacterial hopane derivatives and diplopterol (DPL) were
      detected in all four strains. Based on the 16S rRNA gene sequences, all four
      strains belong to the family Cyclobacteriaceae in the phylum Bacteroidetes.
      Strains JC165(T) and JC169 had a sequence similarity of 97.2% with Mongoliicoccus
      roseus MIM28(T), while strains JC166(T) and JC170 had a sequence similarity of
      99.5% with Litoribacter ruber YIM CH208(T). Strains JC165(T)/JC169 and
      JC166(T)/JC170 had genomic DNA reassociation values (based on DNA-DNA
      hybridization) of 21 +/- 2% and 23 +/- 1% with M. roseus KCTC 19808(T) ( =
      MIM28(T)) and L. ruber KCTC 22899(T) ( = YIM CH208(T)), respectively, suggesting
      that they represented novel species. The reassociation values of >85% between
      strains JC165(T) and JC169, and JC166(T) and JC170 suggested they were strains of
      the same species. The genomic information was supported by phenotypic
      observations leading to the proposal of two novel species, Mongoliicoccus
      alkaliphilus sp. nov. (type strain, JC165(T) = KCTC 32210(T) =LMG 27255(T)) and
      Litoribacter alkaliphilus sp. nov. (type strain, JC166(T) = KCTC 32217(T) =LMG
      27256(T)).

PMID- 23543499
TI  - Muricauda antarctica sp. nov., a marine member of the Flavobacteriaceae isolated
      from Antarctic seawater.
AB  - A Gram-stain-negative, rod-shaped bacterium with appendages, designated Ar-22(T),
      was isolated from a seawater sample collected from the western part of Prydz Bay,
      near Cape Darnley, Antarctica. Strain Ar-22(T) grew optimally at 35  degrees C,
      at pH 7.5 and in the presence of 1-3% (w/v) NaCl. The isolate was positive for
      casein, gelatin and Tween 20 decomposition and negative for H2S production and
      indole formation. Chemotaxonomic analysis showed that MK-6 was the major
      isoprenoid quinone and phosphatidylethanolamine was the major polar lipid. The
      major fatty acids were iso-C(17:0) 3-OH, iso-C(15:1) G, iso-C(15:0) and
      C(16:1)omega7c/iso-C(15:0) 2OH. The genomic DNA G+C content was 44.8 mol%.
      Comparative 16S rRNA gene sequence analysis revealed that strain Ar-22(T) is
      closely related to members of the genus Muricauda, sharing 94.2-97.3% sequence
      similarity with the type strains of species of the genus Muricauda and being most
      closely related to the Muricauda aquimarina. Phylogenetic analysis based on the
      16S rRNA gene sequence comparison confirmed that strain Ar-22(T) formed a deep
      lineage with Muricauda flavescens. Sequence similarity between strain Ar-22(T)
      and Muricauda ruestringensis DSM 13258(T), the type species of the genus
      Muricauda, was 96.9%. Strain Ar-22(T) exhibited mean DNA-DNA relatedness values
      of 40.1%, 49.4% and 25.7% to M. aquimarina JCM 11811(T), M. flavescens JCM
      11812(T) and Muricauda lutimaris KCTC 22173(T), respectively. On the basis of
      phenotypic and genotypic data, strain Ar-22(T) represents a novel species of the
      genus Muricauda, for which the name Muricauda antarctica sp. nov. (type strain Ar
      22(T) =CGMCC 1.12174(T) = JCM 18450(T)) is proposed.

PMID- 23543500
TI  - Flavobacterium aquaticum sp. nov., isolated from a water sample of a rice field.
AB  - Strain JC164(T) was isolated from a water sample from a rice field at Jamdih,
      Mau, Uttar Pradesh, India. Colonies of strain JC164(T) were brown-yellow and
      cells were Gram-stain-negative. Catalase, oxidase and amylase were present. iso
      C(15:0), iso-C(16:0), iso-C15 1 G, iso-C(15:0) 3-OH and iso-C(14:0) were the
      predominant fatty acids with minor amounts of iso-C(16:0) 3-OH, anteiso-C(15:0),
      C(16:0), iso-C(16:1) H, iso-C(14:0) 3-OH and iso-C(13:0). Strain JC164(T)
      contained phosphatidylethanolamine and a few unidentified lipids (L1, L3 and L6)
      as major polar lipids. Bacteriohopane derivative 1 (BHD1) and diplopterol (DPL)
      were the major hopanoids. beta-Carotene was one among the several spirilloxanthin
      series carotenoids present in strain JC164(T). Genomic DNA G+C content was 39.6
      mol%. 16S rRNA gene sequence comparisons indicated that strain JC164(T)
      represents a member of the genus Flavobacterium (family Flavobacteriaceae, class
      Flavobacteriia). The most closely related taxa to strain JC164(T) were
      Flavobacterium sasangense YC6274(T) (98.5%), Flavobacterium cucumis R2A45-3(T)
      (98.1%), Flavobacterium cheniae NJ-26(T) (97.2%) and the novel strain possessed
      <95.1% sequence similarity with other members of the genus Flavobacterium.
      However, strain JC164(T) showed 12.5 +/- 2, 13.6 +/- 1 and 17.4 +/- 2% genomic
      DNA association (based on DNA-DNA hybridization) with Flavobacterium sasangense
      KCTC 22246(T), Flavobacterium cucumis DSM 18830(T) and Flavobacterium cheniae
      CGMCC 1.6844(T), respectively. The distinct genomic difference and morphological,
      physiological and chemotaxonomic differences from the previously described taxa
      support the classification of strain JC164(T) as a representative of a novel
      species of the genus Flavobacterium, for which the name Flavobacterium aquaticum
      sp. nov. is proposed. The type strain is JC164(T) ( = KCTC 32196(T) = CGMCC
      1.12398=LMG 27251(T)).

PMID- 23543501
TI  - Marinoscillum luteum sp. nov., isolated from marine sediment.
AB  - A novel strain, designated SJP7(T), was isolated from sediment of the Tofua Arc
      of the Tonga Trench. The 16S rRNA gene sequence of the isolate showed the highest
      similarity to that of Marinoscillum pacificum KCCM 42325(T) (95.9%). Phylogenetic
      analysis revealed that the isolate formed a distinct phyletic line with
      Marinoscillum pacificum KCCM 42325(T) and Marinoscillum furvescens LMG 13023(T)
      within the family Cytophagaceae. Cells of strain SJP7(T) were Gram-stain-negative
      and appeared as long rods that were motile by gliding. Growth was observed at 15
      40  degrees C (optimum, 30  degrees C), at pH 5.5-9.0 (optimum, pH 7.5-8.0) and
      in the presence of 0.5-7.0% (w/v) NaCl (optimum, 2.5-3%). The major respiratory
      quinone was MK-7. The dominant fatty acids were summed feature 3 (comprising
      C(16:1)omega7c and/or C(16:1)omega6c), iso-C(15:0) and C(16:1)omega5c. The DNA
      G+C content was 43.5 mol%. These properties support the affiliation of strain
      SJP7(T) with the genus Marinoscillum. Further phenotypic differentiation of
      strain SJP7(T) from other species of the genus Marinoscillum was indicated by the
      results of physiological and biochemical tests. On the basis of evidence from our
      polyphasic taxonomic study, strain SJP7(T) represents a novel species of the
      genus Marinoscillum, for which the name Marinoscillum luteum sp. nov. is
      proposed. The type strain of Marinoscillum luteum is SJP7(T) ( =KCTC 23939(T)
      =NCAIM B02491(T)).

PMID- 23543502
TI  - Tenacibaculum xiamenense sp. nov., an algicidal bacterium isolated from coastal
      seawater.
AB  - A Gram-stain-negative, elongated rod-shaped, yellow-pigmented, aerobic bacterial
      strain, designated WJ-1(T), was isolated from coastal seawater in Xiamen, Fujian
      province, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed
      that strain WJ-1(T) fell within the genus Tenacibaculum and was most closely
      associated with Tenacibaculum aestuarii SMK-4(T) (96.7% 16S rRNA gene sequence
      similarity); lower similarities were shown to other members of the genus
      Tenacibaculum (<96.2%). The strain formed a distinct lineage with Tenacibaculum
      litopenaei B-I(T) (96.0%), Tenacibaculum geojense YCS-6(T) (94.5%) and
      Tenacibaculum jejuense CNURIC 013(T) (95.4%). Growth was observed at temperatures
      from 16 to 38  degrees C, at salinities from 2 to 4% and at pH 6-9. The major
      fatty acids were summed feature 3 (C(16:1)omega6c and/or C(16 1)omega7c), iso
      C(17:0) 3-OH, iso-C(15:0) and iso-C(15:0) 3-OH. The DNA G+C content of strain WJ
      1(T) was 33.2 mol% and the major respiratory quinone was menaquinone-6 (MK-6).
      Differential phenotypic properties and phylogenetic distinctiveness in this study
      distinguished strain WJ-1(T) from all other members of the genus Tenacibaculum.
      According to the morphology, physiology, fatty acid composition and 16S rRNA gene
      sequence data, strain WJ-1(T) represents a novel species of the genus
      Tenacibaculum, for which the name Tenacibaculum xiamenense sp. nov. is proposed.
      The type strain is WJ-1(T) ( =CGMCC 1.12378(T) =LMG 27422(T)).

PMID- 23543503
TI  - Niabella hirudinis and Niabella drilacis sp. nov., isolated from the medicinal
      leech Hirudo verbana.
AB  - Two Gram-negative, rod-shaped bacteria, strains E96(T) and E90(T), were isolated
      from medicinal leeches (Hirudo verbana) and characterized by a polyphasic
      taxonomic approach. Phylogenetic analysis based on the nearly full-length 16S
      rRNA gene sequence showed that the two strains shared 98.1% sequence similarity
      and were affiliated with the genus Niabella within the phylum Bacteroidetes, with
      94.4-97.6% sequence similarity to type strains of species of the genus Niabella
      and highest sequence similarity to the type strain of Niabella aurantiaca (97.3
      and 97.6%, respectively). Niabella-related 16S rRNA gene sequences were recently
      detected in the bladders of Hirudo verbana; however, no cultured representatives
      were so far available. Genomic fingerprint analysis using repetitive element
      primed (rep)- and randomly amplified polymorphic DNA (RAPD)-PCRs and DNA-DNA
      hybridization experiments clearly showed that the strains were different from
      each other (DNA-DNA relatedness values of 39.1%, reciprocal 28.0%) and from the
      type strains of N. aurantiaca (<19.7%) and Niabella tibetensis (<41.1%).
      Chemotaxonomic analyses confirmed the affiliation to the genus Niabella. Both
      strains contained MK-7 as the predominant menaquinone. The major fatty acids of
      both strains were iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH and summed feature 3
      (C16:1omega7c and/or iso-C15:0 2-OH), which is characteristic for the genus
      Niabella. Based on genotypic, chemotaxonomic and physiological characterization,
      we propose two novel species of the genus Niabella, Niabella hirudinis sp. nov.,
      with strain E96(T) ( =DSM 25812(T) =CCM 8411(T) =LMG 26956(T)) as the type
      strain, and Niabella drilacis sp. nov., with strain E90(T) ( =DSM 25811(T) =CCM
      8410(T) =LMG 26954(T)) as the type strain.

PMID- 23543504
TI  - Algibacter agarivorans sp. nov. and Algibacter agarilyticus sp. nov., isolated
      from seawater, reclassification of Marinivirga aestuarii as Algibacter aestuarii
      comb. nov. and emended description of the genus Algibacter.
AB  - Two yellow-pigmented, rod-shaped, non-motile, Gram-reaction-negative and aerobic
      bacterial strains, designated KYW560(T) and KYW563(T), were isolated from
      seawater collected from Gwangyang Bay, Republic of Korea. The isolates required
      sea salts for growth. Flexirubin-type pigments were absent. The common major
      cellular fatty acids (>5% of total) of the two strains were C(16:0), C(18:0), iso
      C(15:0), anteiso-C(15:0), iso-C(15:1) G, iso-C(17:0) 3-OH and summed feature 3
      (C(16:1)omega6c and/or C(16:1)omega7c). Strain KYW560(T) also contained iso
      C(15:0) 3-OH and C(20:1)omega9c as major fatty acids. The main polar lipids were
      phosphatidylethanolamine, an unidentified aminolipid and two unidentified lipids.
      The predominant isoprenoid quinone was MK-6. The DNA G+C contents of strains
      KYW560(T) and KYW563(T) were 41.0 +/- 0.7 and 38.3 +/- 0.4 mol% (mean +/- sd of
      three determinations), respectively. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that the isolates belonged to the family Flavobacteriaceae,
      and were related to the genus Algibacter. Based on data from this taxonomic study
      using a polyphasic approach, it is proposed that the isolates represent novel
      species of the genus Algibacter, for which the names Algibacter agarivorans sp.
      nov. (type strain, KYW560(T) =KCTC 23855(T) =JCM 18285(T)) and Algibacter
      agarilyticus sp. nov. (type strain, KYW563(T) =KCTC 23857(T) =JCM 18275(T)) are
      proposed. Reclassification of Marinivirga aestuarii as Algibacter aestuarii comb.
      nov. and emended description of the genus Algibacter are also proposed.

PMID- 23543505
TI  - A Study on the HBV and the HCV Infections in Female Sex Workers and their Co
      Infection with HIV.
AB  - BACKGROUND: Sexually Transmitted Infections (STIs) have been shown to enhance the
      transmission of the Human Immunodeficiency Virus (HIV). The Hepatitis B and the
      Hepatitis C viral infections are highly prevalent among the HIV-infected persons
      as a result of shared transmission routes. AIM: To determine the seroprevalence
      of the HIV, Syphilis, HBV and HCV infections and their co-infection rates among
      Female Sex Workers (FSWs). SETTINGS AND DESIGN: 250 blood samples were collected
      from FSWs from a red light area of Mumbai by using an outreach strategy.
      MATERIALS AND METHODS: Their sera were tested for the HIV antibodies as per the
      strategy II of the NACO guidelines, for syphilis by RPR, for the HCV antibodies
      and for HBsAg by ELISA. RESULTS: The study group showed (105/250) 42% HIV
      reactivity, (15/250) 6% RPR reactivity, (20/250) 8% HBsAg positivity, (7/250)
      2.8% HCV reactivity, (11/250) 4.4% HIV-RPR reactivity, (7/250) 2.8% HIV-HBV co
      infection and (3/250)1.2% HIV-HCV co-infection. Statistical test which was used:
      The Chi square test. CONCLUSION: A high HIV sero-prevalence was found among the
      FSWs. A high HIV prevalence was found among the RPR reactive FSWs. The
      relationship between the HIV reactivity and the RPR reactivity was statistically
      significant. Co-infections with HBV and HCV were detected among the HIV reactive
      FSWs, but they were not statistically significant.

PMID- 23543506
TI  - Physiological and tumoral uptake of (68)Ga-DOTATATE: standardized uptake values
      and challenges in interpretation.
AB  - PURPOSE: The objective of this study is to determine the range of SUVmax of 68Ga
      DOTATATE in normal organs and tumoral lesions and establish uptake unrelated to
      NET. MATERIALS AND METHODS: One hundred and twenty patients (57 men, 63 women),
      who underwent (68)Ga-DOTATATE PET/CT imaging in our institution were analyzed.
      Patients were indicated for (68)Ga-DOTATATE PET/CT imaging to detect primary
      tumor or metastasis of suspected or previously known NET, to determine SSTR
      positivity and to detect occult source of ectopic Cushing syndrome. Normal range
      of uptake was calculated for the organs that were proven to have no pathology by
      either conventional radiological imaging or clinical follow-up, using SUVmax as a
      semiquantitative measure. Uptake and tumor to background (T/B) ratios of tumoral
      lesions in liver, pancreas, bone, brain and lymph nodes were calculated. Uptakes
      due to lesions unrelated to NET were also documented. RESULTS: Significant uptake
      was found in spleen, kidneys, adrenal glands, liver and pituitary gland with mean
      SUVmax of 24.67, 14.30, 13.73, 9.12 and 9.74 respectively. Uptake was measured
      separately for the pancreatic head and body separately, however, besides a
      slightly heterogeneous uptake; the difference was not statistically significant.
      Uptake in the tumoral lesions had high (T/B) ratios with mean SUVmax of 28.72,
      25.21, 18.28, 34.73 and 12.59 for liver, pancreas, bone, brain and lymph nodes,
      respectively. Incidental benign tumoral lesions were detected in 3 patients (2.5
      %) which were meningioma and fibrous dysplasia demonstrating significant and
      breast fibroadenoma demonstrating mild (68)Ga-DOTATATE uptake. Non-neoplastic
      processes were detected in 4 patients (14.1 %), including postsurgical
      inflammation, reactive lymph nodes, arthritis and demonstrated faint to mild
      (68)Ga-DOTATATE uptake, with the exception of significant uptake in accessory
      spleen. CONCLUSION: (68)Ga-DOTATATE has high T/B ratio with physiological
      biodistribution comparable to its counterparts. However, the presence of SSTRs in
      benign and malignant lesions unrelated to NET may be challenging in
      interpretation particularly where the physiological uptake is variable.

PMID- 23543507
TI  - Interactive ontology debugging: Two query strategies for efficient fault
      localization.
AB  - Effective debugging of ontologies is an important prerequisite for their broad
      application, especially in areas that rely on everyday users to create and
      maintain knowledge bases, such as the Semantic Web. In such systems ontologies
      capture formalized vocabularies of terms shared by its users. However in many
      cases users have different local views of the domain, i.e. of the context in
      which a given term is used. Inappropriate usage of terms together with natural
      complications when formulating and understanding logical descriptions may result
      in faulty ontologies. Recent ontology debugging approaches use diagnosis methods
      to identify causes of the faults. In most debugging scenarios these methods
      return many alternative diagnoses, thus placing the burden of fault localization
      on the user. This paper demonstrates how the target diagnosis can be identified
      by performing a sequence of observations, that is, by querying an oracle about
      entailments of the target ontology. To identify the best query we propose two
      query selection strategies: a simple "split-in-half" strategy and an entropy
      based strategy. The latter allows knowledge about typical user errors to be
      exploited to minimize the number of queries. Our evaluation showed that the
      entropy-based method significantly reduces the number of required queries
      compared to the "split-in-half" approach. We experimented with different
      probability distributions of user errors and different qualities of the a priori
      probabilities. Our measurements demonstrated the superiority of entropy-based
      query selection even in cases where all fault probabilities are equal, i.e. where
      no information about typical user errors is available.

PMID- 23543508
TI  - Early trophic feeding versus enteral fasting for very preterm or very low birth
      weight infants.
AB  - BACKGROUND: The introduction of enteral feeds for very preterm (< 32 weeks) or
      very low birth weight (< 1500 grams) infants is often delayed due to concern that
      early introduction may not be tolerated and may increase the risk of necrotising
      enterocolitis. However, prolonged enteral fasting may diminish the functional
      adaptation of the immature gastrointestinal tract and extend the need for
      parenteral nutrition with its attendant infectious and metabolic risks. Trophic
      feeding, giving infants very small volumes of milk to promote intestinal
      maturation, may enhance feeding tolerance and decrease the time taken to reach
      full enteral feeding independently of parenteral nutrition. OBJECTIVES: To
      determine the effect of early trophic feeding versus enteral fasting on feed
      tolerance, growth and development, and the incidence of neonatal morbidity
      (including necrotising enterocolitis and invasive infection) and mortality in
      very preterm or VLBW infants. SEARCH METHODS: We used the standard search
      strategy of the Cochrane Neonatal Review Group. This included electronic searches
      of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2012, Issue 12), MEDLINE, EMBASE and CINAHL (1980 until December 2012),
      conference proceedings and previous reviews. SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials that assessed the effects of early trophic
      feeding (milk volumes up to 24 ml/kg/day introduced before 96 hours postnatal age
      and continued until at least one week after birth) versus a comparable period of
      enteral fasting in very preterm or very low birth weight infants. DATA COLLECTION
      AND ANALYSIS: We extracted data using the standard methods of the Cochrane
      Neonatal Review Group with separate evaluation of trial quality and data
      extraction by two authors and synthesis of data using risk ratio, risk difference
      and mean difference. MAIN RESULTS: Nine trials in which a total of 754 very
      preterm or very low birth weight infants participated were eligible for
      inclusion. Few participants were extremely preterm (< 28 weeks) or extremely low
      birth weight (< 1000 grams) or growth restricted. These trials did not provide
      any evidence that early trophic feeding affected feed tolerance or growth rates.
      Meta-analysis did not detect a statistically significant effect on the incidence
      of necrotising enterocolitis: typical risk ratio 1.07 (95% confidence interval
      0.67 to 1.70); risk difference 0.01 (-0.03 to 0.05). AUTHORS' CONCLUSIONS: The
      available trial data do not provide evidence of important beneficial or harmful
      effects of early trophic feeding for very preterm or very low birth weight
      infants. The applicability of these findings to extremely preterm, extremely low
      birth weight or growth restricted infants is limited. Further randomised
      controlled trials would be needed to determine how trophic feeding compared with
      enteral fasting affects important outcomes in this population.

PMID- 23543509
TI  - Buflomedil for intermittent claudication.
AB  - BACKGROUND: Intermittent claudication (IC) is pain caused by chronic occlusive
      arterial disease, that develops in a limb during exercise and is relieved with
      rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease.
      However, its clinical efficacy for IC has not yet been critically examined. This
      is an update of a Cochrane review first published in 2000, and previously updated
      in 2007 and 2008. OBJECTIVES: To evaluate the available evidence on the efficacy
      of buflomedil for IC. SEARCH METHODS: For this update the Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator searched the Specialised
      Register (last searched January 2013) and CENTRAL (2012, Issue 12). SELECTION
      CRITERIA: Double-blinded, randomized controlled trials (RCTs) in patients with IC
      (Fontaine stage II) receiving oral buflomedil compared with placebo. Pain-free
      walking distance (PFWD) and maximum walking distance (MWD) were analysed by
      standardized exercise test. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted study
      authors for additional information. MAIN RESULTS: We included two RCTs with 127
      participants. Both RCTs showed moderate improvements in PFWD for patients on
      buflomedil. This improvement was statistically significant for both trials (WMD
      75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to
      158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains
      were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI
      9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively. AUTHORS'
      CONCLUSIONS: There is little evidence available to evaluate the efficacy of
      buflomedil for IC. Most trials were excluded due to poor quality. The two
      included trials showed moderately positive results; these are undermined by
      publication bias since we know of at least another four unpublished,
      irretrievable, and inconclusive studies.Buflomedil's benefit is small in relation
      to safety issues and its narrow therapeutic range.

PMID- 23543510
TI  - WITHDRAWN: Non-steroidal anti-inflammatory drugs for preventing heterotopic bone
      formation after hip arthroplasty.
AB  - BACKGROUND: Heterotopic bone formation (HBF) in the soft tissues surrounding the
      hip joint is a frequent complication of hip surgery. Non-steroidal anti
      inflammatory drugs (NSAIDs) administered in the immediate perioperative period
      reduce the risk of HBF. However, the magnitude of the effect on HBF, and the
      effects on other associated outcomes, such as pain and physical function, are
      uncertain. OBJECTIVES: To determine the effects of perioperative NSAID therapy
      versus control on the risk of HBF and other outcomes in patients undergoing hip
      arthroplasty. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle
      Trauma Group specialised register (October 2002), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library issue 3, 2002), MEDLINE (1966 to
      October 2002), EMBASE (1988 to 2002 Week 43), CURRENT CONTENTS (1993 Week 27 to
      2002 Week 44) and reference lists of articles. We also contacted trialists and
      drug manufacturers. SELECTION CRITERIA: All trials which enrolled patients
      scheduled to undergo hip arthroplasty with random or quasi-random allocation to
      perioperative NSAID or control and that recorded post-operative radiographically
      determined HBF. The primary outcome was post-operative radiographic HBF.
      Secondary outcomes were pain, function (including range of motion), gastro
      intestinal and other bleeding complications, and other causes of major morbidity
      or mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      methodological quality and extracted data. All analyses were conducted on
      dichotomised outcomes. MAIN RESULTS: Sixteen randomised and two quasi-randomised
      trials involving a total of 4,763 patients were included. Overall, in 17 trials
      that examined the effects of medium to high doses of NSAIDs, there was a reduced
      risk of developing HBF after hip surgery (59% reduction, 95% confidence interval
      54% to 64% reduction). In contrast, one large trial examining low-dose aspirin,
      demonstrated no effect on the risk of HBF (2% reduction, 95% confidence interval
      15% reduction to 12% increase). There was strong evidence of differences in the
      size of the treatment effects observed between the trials examining medium to
      high doses of NSAIDs, but reasons were not clearly identified.There was a non
      significant one third increased risk of gastro-intestinal side effects among
      patients assigned NSAIDs (29% increase, 95% confidence interval 0% to 76%
      increase). Most of this increase was due to an increased risk of minor gastro
      intestinal complications. Data on the late post-operative outcomes of pain,
      impaired physical function and range of joint movement were few and no formal
      overviews of the effects of NSAIDs on these outcomes were possible. AUTHORS'
      CONCLUSIONS: Perioperative NSAIDs, apart from low dose aspirin, appear to produce
      between a one half and two thirds reduction in the risk of HBF. With routine use,
      such agents may be able to prevent 15-20 cases of HBF among every 100 total hip
      replacements performed. However, while medium to high doses of perioperative
      NSAIDs clearly produce a substantial reduction in the incidence of radiographic
      HBF, there remains some uncertainty about short-term side effects of treatment
      and substantial uncertainty about effects on long-term clinical outcomes such as
      chronic pain and impaired physical function. The net effect of routine HBF
      prophylaxis with NSAIDs requires formal assessment in a randomised trial designed
      to determine the balance of benefits and risks for all outcomes.

PMID- 23543511
TI  - Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in
      very low birth weight infants.
AB  - BACKGROUND: Early enteral feeding practices are potentially modifiable risk
      factors for necrotising enterocolitis in very preterm or very low birth weight
      (VLBW) infants. Observational studies suggest that conservative feeding regimens
      that include slowly advancing enteral feed volumes reduce the risk of necrotising
      enterocolitis. However, slow feed advancement may delay establishment of full
      enteral feeding and be associated with metabolic and infectious morbidities
      secondary to prolonged exposure to parenteral nutrition. OBJECTIVES: To determine
      the effect of slow rates of enteral feed advancement on the incidence of
      necrotising enterocolitis, mortality and other morbidities in very preterm or
      VLBW infants. SEARCH METHODS: We used the standard search strategy of the
      Cochrane Neonatal Review Group. We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE,
      EMBASE and CINAHL (to December 2012), conference proceedings, and previous
      reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials
      that assessed the effect of slow (up to 24 ml/kg/day) versus faster rates of
      advancement of enteral feed volumes upon the incidence of necrotising
      enterocolitis in very preterm or VLBW infants. DATA COLLECTION AND ANALYSIS: Data
      collection and analysis was performed using the standard methods of the Cochrane
      Neonatal Review Group. MAIN RESULTS: We identified five randomised controlled
      trials in which a total of 588 infants participated. Few participants were
      extremely preterm, extremely low birth weight or growth restricted. The trials
      defined slow advancement as daily increments of 15 to 20 ml/kg and faster
      advancement as 30 to 35 ml/kg. Meta-analyses did not detect statistically
      significant effects on the risk of necrotising enterocolitis (typical risk ratio
      (RR) 0.97, 95% confidence interval (CI) 0.54 to 1.74) or all-cause mortality (RR
      1.41, 95% CI 0.81 to 2.74). Infants who had slow advancement took significantly
      longer to regain birth weight (reported median differences two to six days) and
      to establish full enteral feeding (two to five days). AUTHORS' CONCLUSIONS: The
      available trial data suggest that advancing enteral feed volumes at slow rather
      than faster rates does not reduce the risk of necrotising enterocolitis in very
      preterm or VLBW infants. Advancing the volume of enteral feeds at slow rates
      results in several days delay in regaining birth weight and establishing full
      enteral feeds but the long term clinical importance of these effects is unclear.
      The applicability of these findings to extremely preterm, extremely low birth
      weight or growth restricted infants is limited. Further randomised controlled
      trials in these populations may be warranted to resolve this uncertainty.

PMID- 23543512
TI  - Sealants for preventing dental decay in the permanent teeth.
AB  - BACKGROUND: Dental sealants were introduced in the 1960s to help prevent dental
      caries in the pits and fissures of mainly the occlusal tooth surfaces. Sealants
      act to prevent the growth of bacteria that can lead to dental decay. There is
      evidence to suggest that fissure sealants are effective in preventing caries in
      children and adolescents when compared to no sealants. Their effectiveness may be
      related to the caries prevalence in the population. OBJECTIVES: To compare the
      effects of different types of fissure sealants in preventing caries in permanent
      teeth in children and adolescents. SEARCH METHODS: We searched the Cochrane Oral
      Health Group's Trials Register (to 1 November 2012); the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7);
      MEDLINE via OVID (1946 to 1 November 2012); EMBASE via OVID (1980 to 1 November
      2012); SCISEARCH, CAplus, INSPEC, NTIS and PASCAL via STN Easy (to 1 September
      2012); and DARE, NHS EED and HTA (via the CAIRS web interface to 29 March 2012
      and thereafter via Metaxis interface to September 2012). There were no language
      or publication restrictions. We also searched for ongoing trials via
      ClinicalTrials.gov (to 23 July 2012). SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials of at least 12 months duration comparing sealants
      for preventing caries of occlusal or approximal surfaces of premolar or molar
      teeth with no sealant or different type of sealant in children and adolescents
      under 20 years of age. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened search results, extracted data and assessed trial quality.
      We calculated the odds ratio (OR) for caries or no caries on occlusal surfaces of
      permanent molar teeth. For trials with a split-mouth design, the Becker-Balagtas
      odds ratio was used. For mean caries increment we used the mean difference. All
      measures are presented with 95% confidence intervals (CI). The quality of the
      evidence was assessed using GRADE methods. We conducted the meta-analyses using a
      random-effects model for those comparisons where there were more than three
      trials in the same comparison, otherwise the fixed-effect model was used. MAIN
      RESULTS: Thirty-four trials are included in the review. Twelve trials evaluated
      the effects of sealant compared with no sealant (2575 participants) (one of those
      12 trials stated only number of tooth pairs); 21 trials evaluated one type of
      sealant compared with another (3202 participants); and one trial evaluated two
      different types of sealant and no sealant (752 participants). Children were aged
      from 5 to 16 years. Trials rarely reported the background exposure to fluoride of
      the trial participants or the baseline caries prevalence.- Resin-based sealant
      compared with no sealant: Compared to control without sealant, second or third or
      fourth generation resin-based sealants prevented caries in first permanent molars
      in children aged 5 to 10 years (at 2 years of follow-up odds ratio (OR) 0.12, 95%
      confidence interval (CI) 0.07 to 0.19, six trials (five published in the 1970s
      and one in 2012), at low risk of bias, 1259 children randomised, 1066 children
      evaluated, moderate quality evidence). If we were to assume that 40% of the
      control tooth surfaces were decayed during 2 years of follow-up (400 carious
      teeth per 1000), then applying a resin-based sealant will reduce the proportion
      of the carious surfaces to 6.25% (95% CI 3.84% to 9.63%); similarly if we were to
      assume that 70% of the control tooth surfaces were decayed  (700 carious teeth
      per 1000), then applying a resin-based sealant will reduce the proportion of the
      carious surfaces to 18.92% (95% CI 12.28% to 27.18%). This caries preventive
      effect was maintained at longer follow-up but both the quality and quantity of
      the evidence was reduced (e.g. at 48 to 54 months of follow-up OR 0.21, 95% CI
      0.16 to 0.28, four trials (two studies at low risk of bias and two studies at
      high risk of bias), 482 children evaluated; risk ratio (RR) 0.24, 95% CI 0.12 to
      0.45, one study at unclear risk of bias, 203 children evaluated).- Glass ionomer
      sealant compared with no sealant: There is insufficient evidence to make any
      conclusions about whether glass ionomer sealants, prevent caries compared to no
      sealant at 24-month follow-up (mean difference in DFS -0.18, 95% CI -0.39 to
      0.03, one trial at unclear risk of bias, 452 children randomised, 404 children
      evaluated, very low quality evidence).- Sealant compared with another sealant:
      The relative effectiveness of different types of sealants remained inconclusive
      in this review. Twenty-one trials directly compared two different sealant
      materials. Several different comparisons were made according to type of sealant,
      outcome measure and duration of follow-up. There was great variation with regard
      to comparisons, outcomes, time of outcomes reported and background fluoride
      exposure if this was reported.Fifteen trials compared glass ionomer with resin
      sealants and there is insufficient evidence to make any conclusions about the
      superiority of either of the two materials. Although there were 15 trials the
      event rate was very low in many of these which restricted their contribution to
      the results.Three trials compared resin-modified glass ionomer with resin sealant
      and reported inconsistent results.Two small low quality trials compared polyacid
      modified resin sealants with resin sealants and found no difference in caries
      after 2 years.- Adverse effects: Only two trials mentioned adverse effects and
      stated that no adverse effects were reported by participants. AUTHORS'
      CONCLUSIONS: The application of sealants is a recommended procedure to prevent or
      control caries. Sealing the occlusal surfaces of permanent molars in children and
      adolescents reduces caries up to 48 months when compared to no sealant, after
      longer follow-up the quantity and quality of the evidence is reduced. The review
      revealed that sealants are effective in high risk children but information on the
      magnitude of the benefit of sealing in other conditions is scarce. The relative
      effectiveness of different types of sealants has yet to be established.

PMID- 23543513
TI  - Dressings for superficial and partial thickness burns.
AB  - BACKGROUND: An acute burn wound is a complex and evolving injury. Extensive burns
      produce systemic consequences, in addition to local tissue damage. Treatment of
      partial thickness burn wounds is directed towards promoting healing and a wide
      variety of dressings are currently available. Improvements in technology and
      advances in understanding of wound healing have driven the development of new
      dressings. Dressing selection should be based on their effects on healing, but
      ease of application and removal, dressing change requirements, cost and patient
      comfort should also be considered. OBJECTIVES: To assess the effects of burn
      wound dressings on superficial and partial thickness burns. SEARCH METHODS: For
      this first update we searched The Cochrane Wounds Group Specialised Register
      (searched 8 November 2012); The Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2012, Issue 10); Ovid MEDLINE (2008 to October
      Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, November
      07, 2012); Ovid EMBASE (2008 to 2012 Week 44); AND EBSCO CINAHL (1982 to 2
      November 2012). SELECTION CRITERIA: All randomised controlled trials (RCTs) that
      evaluated the effects of burn wound dressings on the healing of superficial and
      partial thickness burns. DATA COLLECTION AND ANALYSIS: Two authors extracted the
      data independently using standardised forms. We assessed each trial for internal
      validity and resolved differences by discussion. MAIN RESULTS: A total of 30 RCTs
      are included in this review. Overall both the quality of trial reporting and
      trial conduct were generally poor and meta analysis was largely precluded due to
      study heterogeneity or poor data reporting. In the context of this poor quality
      evidence, silver sulphadiazine (SSD) was consistently associated with poorer
      healing outcomes than biosynthetic (skin substitute) dressings, silver-containing
      dressings and silicon-coated dressings. Burns treated with hydrogel dressings
      appear to heal more quickly than those treated with usual care. AUTHORS'
      CONCLUSIONS: There is a paucity of high-quality evidence regarding the effect of
      different dressings on the healing of superficial and partial thickness burn
      injuries. The studies summarised in this review evaluated a variety of
      interventions, comparators and clinical endpoints and all were at risk of bias.
      It is impossible to draw firm and confident conclusions about the effectiveness
      of specific dressings, however silver sulphadiazine was consistently associated
      with poorer healing outcomes than biosynthetic, silicon-coated and silver
      dressings whilst hydrogel-treated burns had better healing outcomes than those
      treated with usual care.

PMID- 23543514
TI  - Dietary advice for reducing cardiovascular risk.
AB  - BACKGROUND: Changes in population diet are likely to reduce cardiovascular
      disease and cancer, but the effect of dietary advice is uncertain. This review is
      an update of a previous review published in 2007. OBJECTIVES: To assess the
      effects of providing dietary advice to achieve sustained dietary changes or
      improved cardiovascular risk profile among healthy adults. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials, the Database of
      Abstracts of Reviews of Effects (DARE) and the HTA database on The Cochrane
      Library (Issue 4, 2010). We searched MEDLINE (Ovid) (1950 to week 2 October 2010)
      and EMBASE (Ovid) (1980 to Week 42 2010). Additional searches were done on CAB
      Health (1972 to December 1999), CVRCT registry (2000), CCT (2000) and SIGLE (1980
      to 2000). Dissertation abstracts and reference lists of articles were checked and
      researchers were contacted. SELECTION CRITERIA: Randomised studies with no more
      than 20% loss to follow-up, lasting at least three months and involving healthy
      adults comparing dietary advice with no advice or minimal advice. Trials
      involving children, trials to reduce weight or those involving supplementation
      were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted data. Study authors were contacted for
      additional information. MAIN RESULTS: Forty-four trials with 52 intervention arms
      (comparisons) comparing dietary advice with no advice were included in the
      review; 18,175 participants or clusters were randomised. Twenty-nine of the 44
      included trials were conducted in the USA. Dietary advice reduced total serum
      cholesterol by 0.15 mmol/L (95% CI 0.06 to 0.23) and LDL cholesterol by 0.16
      mmol/L (95% CI 0.08 to 0.24) after 3 to 24 months. Mean HDL cholesterol levels
      and triglyceride levels were unchanged. Dietary advice reduced blood pressure by
      2.61 mm Hg systolic (95% CI 1.31 to 3.91) and 1.45 mm Hg diastolic (95% CI 0.68
      to 2.22) and 24-hour urinary sodium excretion by 40.9 mmol (95% CI 25.3 to 56.5)
      after 3 to 36 months but there was heterogeneity between trials for the latter
      outcome. Three trials reported plasma antioxidants, where small increases were
      seen in lutein and beta-cryptoxanthin, but there was heterogeneity in the trial
      effects. Self-reported dietary intake may be subject to reporting bias, and there
      was significant heterogeneity in all the following analyses. Compared to no
      advice, dietary advice increased fruit and vegetable intake by 1.18 servings/day
      (95% CI 0.65 to 1.71). Dietary fibre intake increased with advice by 6.5 g/day
      (95% CI 2.2 to 10.82), while total dietary fat as a percentage of total energy
      intake fell by 4.48% (95% CI 2.47 to 6.48) with dietary advice, and saturated fat
      intake fell by 2.39% (95% CI 1.4 to 3.37).Two trials analysed incident
      cardiovascular disease (CVD) events (TOHP I/II). Follow-up was 77% complete at 10
      to 15 years after the end of the intervention period and estimates of event rates
      lacked precision but suggested that sodium restriction advice probably led to a
      reduction in cardiovascular events (combined fatal plus non-fatal events) plus
      revascularisation (TOHP I hazards ratio (HR) 0.59, 95% CI 0.33 to 1.08; TOHP II
      HR 0.81, 95% CI 0.59 to 1.12). AUTHORS' CONCLUSIONS: Dietary advice appears to be
      effective in bringing about modest beneficial changes in diet and cardiovascular
      risk factors over approximately 12 months, but longer-term effects are not known.

PMID- 23543515
TI  - Interprofessional education: effects on professional practice and healthcare
      outcomes (update).
AB  - BACKGROUND: The delivery of effective, high-quality patient care is a complex
      activity. It demands health and social care professionals collaborate in an
      effective manner. Research continues to suggest that collaboration between these
      professionals can be problematic. Interprofessional education (IPE) offers a
      possible way to improve interprofessional collaboration and patient care.
      OBJECTIVES: To assess the effectiveness of IPE interventions compared to
      separate, profession-specific education interventions; and to assess the
      effectiveness of IPE interventions compared to no education intervention. SEARCH
      METHODS: For this update we searched the Cochrane Effective Practice and
      Organisation of Care Group specialised register, MEDLINE and CINAHL, for the
      years 2006 to 2011. We also handsearched the Journal of Interprofessional Care
      (2006 to 2011), reference lists of all included studies, the proceedings of
      leading IPE conferences, and websites of IPE organisations. SELECTION CRITERIA:
      Randomised controlled trials (RCTs), controlled before and after (CBA) studies
      and interrupted time series (ITS) studies of IPE interventions that reported
      objectively measured or self reported (validated instrument) patient/client or
      healthcare process outcomes. DATA COLLECTION AND ANALYSIS: At least two review
      authors independently assessed the eligibility of potentially relevant studies.
      For included studies, at least two review authors extracted data and assessed
      study quality. A meta-analysis of study outcomes was not possible due to
      heterogeneity in study designs and outcome measures. Consequently, the results
      are presented in a narrative format. MAIN RESULTS: This update located nine new
      studies, which were added to the six studies from our last update in 2008. This
      review now includes 15 studies (eight RCTs, five CBA and two ITS studies). All of
      these studies measured the effectiveness of IPE interventions compared to no
      educational intervention. Seven studies indicated that IPE produced positive
      outcomes in the following areas: diabetes care, emergency department culture and
      patient satisfaction; collaborative team behaviour and reduction of clinical
      error rates for emergency department teams; collaborative team behaviour in
      operating rooms; management of care delivered in cases of domestic violence; and
      mental health practitioner competencies related to the delivery of patient care.
      In addition, four of the studies reported mixed outcomes (positive and neutral)
      and four studies reported that the IPE interventions had no impact on either
      professional practice or patient care. AUTHORS' CONCLUSIONS: This updated review
      reports on 15 studies that met the inclusion criteria (nine studies from this
      update and six studies from the 2008 update). Although these studies reported
      some positive outcomes, due to the small number of studies and the heterogeneity
      of interventions and outcome measures, it is not possible to draw generalisable
      inferences about the key elements of IPE and its effectiveness. To improve the
      quality of evidence relating to IPE and patient outcomes or healthcare process
      outcomes, the following three gaps will need to be filled: first, studies that
      assess the effectiveness of IPE interventions compared to separate, profession
      specific interventions; second, RCT, CBA or ITS studies with qualitative strands
      examining processes relating to the IPE and practice changes; third, cost-benefit
      analyses.

PMID- 23543516
TI  - Calcium antagonists as an add-on therapy for drug-resistant epilepsy.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in The Cochrane Library 2001, Issue 4.Nearly a third of people with epilepsy do
      not have their seizures controlled with current treatments. Continuous attempts
      have been made to find new antiepileptic drugs based on increasing knowledge of
      the cellular and molecular biology involved in the genesis of epilepsy and
      seizures. Therefore, calcium antagonists that can alter the effects of calcium on
      brain cells have been investigated for their effect on epileptic seizures.
      OBJECTIVES: To evaluate the effects of calcium antagonists when used as an add-on
      therapy for people with drug-resistant epilepsy. SEARCH METHODS: We searched the
      Cochrane Epilepsy Group Specialized Register (29 January 2013), Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12),
      MEDLINE (1948 to 29 January 2013) and SCOPUS (all years to 29 January 2013).
      SELECTION CRITERIA: Randomised placebo-controlled or active-controlled add-on
      trials of any calcium antagonist in people with drug-resistant epilepsy. DATA
      COLLECTION AND ANALYSIS: Two review authors (MH and JP) independently selected
      trials for inclusion and extracted data. Outcomes investigated included 50% or
      greater reduction in seizure frequency, treatment withdrawal, adverse effects,
      cognition and quality of life. Analyses were by intention to treat. MAIN RESULTS:
      Eleven trials were included with a total of 424 participants, one parallel-group
      and seven cross-over trials of flunarizine, two cross-over trials of nimodipine
      and one cross-over trial of nifedipine.For flunarizine, the risk ratio (RR) with
      95% confidence interval (CI) for a 50% or greater reduction in seizure frequency
      in a single parallel trial was 1.53 (95% CI 0.59 to 3.96) indicating a non
      significant advantage of flunarizine. We were unable to acquire data for this
      outcome from the other seven cross-over trials. The overall RR for treatment
      withdrawal of flunarizine was 7.11 (95% CI 1.73 to 29.30) indicating individuals
      were significantly more likely to have flunarizine withdrawn than placebo. No
      adverse effects were associated statistically with flunarizine.For nifedipine, we
      were unable to acquire the data we required for our specified outcomes.For
      nimodipine, we had data only from the first treatment period from one of the two
      cross-over trials (17 participants). The RR for a 50% or greater reduction in
      seizure frequency was 7.78 (99% CI 0.46 to 130.88) and for treatment withdrawal
      the RR was 2.25 (99% CI 0.25 to 20.38). AUTHORS' CONCLUSIONS: Flunarizine may
      have a weak effect on seizure frequency but had a significant withdrawal rate,
      probably due to adverse effects, and should not be recommended for use as an add
      on treatment. Similarly, there is no convincing evidence to support the use of
      nifedipine or nimodipine as add-on treatments for epilepsy.

PMID- 23543517
TI  - WITHDRAWN: Different functional treatment strategies for acute lateral ankle
      ligament injuries in adults.
AB  - BACKGROUND: Acute lateral ankle ligament ruptures are common problems in present
      health care. Early mobilisation and functional treatment are advocated as a
      preferable treatment strategy. However, functional treatment comprises a broad
      spectrum of treatment strategies and as of yet no optimal strategy has been
      identified. OBJECTIVES: The objective of this review is to assess different
      functional treatment strategies for acute lateral ankle ligament ruptures in
      adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group specialised register (December 2001), the Cochrane Controlled Trials
      Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966 to May 2000),
      EMBASE (1980 to May 2000), CURRENT CONTENTS (1993 to 1999), BIOSIS (to 1999),
      reference lists of articles, and contacted organisations and researchers in the
      field. SELECTION CRITERIA: Randomised clinical trials describing skeletally
      mature individuals with an acute lateral ankle ligament rupture and comparing
      different functional treatment strategies were evaluated for inclusion. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of
      included trials and extracted relevant data on treatment outcome. Where
      appropriate, results of comparable studies were pooled. Individual and pooled
      statistics are reported as relative risks (RR) for dichotomous outcome and
      (weighted) mean differences (WMD) for continuous outcome measures with 95 per
      cent confidence intervals (95%CI). Heterogeneity between trials was tested using
      a standard chi-squared test. MAIN RESULTS: Nine trials involving 892 participants
      were included. Lace-up ankle support had significantly better results for
      persistent swelling at short-term follow up when compared with semi-rigid ankle
      support (RR 4.19, 95% CI 1.26 to 13.98); elastic bandage (RR 5.48; 95% CI 1.69 to
      17.76); and to tape (RR 4.07, 95% CI 1.21 to 13.68). Use of a semi-rigid ankle
      support resulted in a significantly shorter time to return to work when compared
      with an elastic bandage (WMD (days) 4.24; 95% CI 2.42 to 6.06); one trial found
      the use of a semi-rigid ankle support saw a significantly quicker return to sport
      compared with elastic bandage (RR 9.60; 95% CI 6.34 to 12.86) and another trial
      found fewer patients reported instability at short-term follow-up when treated
      with a semi-rigid support than with an elastic bandage (RR 8.00; 95% CI 1.03 to
      62.07). Tape treatment resulted in significantly more complications, the majority
      being skin irritations, when compared with treatment with an elastic bandage (RR
      0.11; 95% CI 0.01 to 0.86). No other results showed statistically significant
      differences. AUTHORS' CONCLUSIONS: The use of an elastic bandage has fewer
      complications than taping but appears to be associated with a slower return to
      work and sport, and more reported instability than a semi-rigid ankle support.
      Lace-up ankle support appears to be effective in reducing swelling in the short
      term compared with semi-rigid ankle support, elastic bandage and tape. However,
      definitive conclusions are hampered by the variety of treatments used, and the
      inconsistency of reported follow-up times. The most effective treatment, both
      clinically and in costs, is unclear from currently available randomised trials.

PMID- 23543518
TI  - Artichoke leaf extract for treating hypercholesterolaemia.
AB  - BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk
      for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf
      extract (ALE) has been implicated in lowering cholesterol levels. Whether ALE is
      truly effective for this indication is still a matter of debate. This is an
      update of a review first published in 2002 and last updated in 2009. OBJECTIVES:
      To assess the efficacy and safety of ALE in the treatment of
      hypercholesterolaemia., SEARCH METHODS: We updated searches of the Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library) (2012,
      Issue 5); MEDLINE Ovid (1966 to May Week 2, 2012); EMBASE Ovid (1980 to 2012 Week
      19); and CINAHL Ebsco (1982 to May 2012) on 17 May 2012. CISCOM was last searched
      until June 2001, and AMED until June 2008. We checked reference lists of
      articles, and contacted manufacturers of preparations containing artichoke
      extract, and experts on the subject. No language restrictions were applied.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) of ALE mono
      preparations compared with placebo or reference medication for patients with
      hypercholesterolaemia. We excluded trials assessing ALE as one of several active
      components in a combination preparation or as a part of a combination treatment.
      DATA COLLECTION AND ANALYSIS: Data were extracted systematically and risk of bias
      was evaluated using the Cochrane 'Risk of bias' tool. Two authors independently
      performed the screening of studies, selection, data extraction and assessment of
      risk of bias. Disagreements in the evaluation of individual trials were resolved
      through discussion. MAIN RESULTS: We included three RCTs involving 262
      participants. The trials were of adequate methodological quality but had some
      shortcomings. One trial was at low quality of risk, one at medium and one of
      unclear risk of bias. One trial is available as abstract only and includes a
      small sample. In the first trial the total cholesterol level in participants
      receiving ALE decreased by 4.2% from 7.16 (0.62) mmol/L to 6.86 (0.68) mmol/L
      after 12 weeks, and increased from 6.90 (0.49) mmol/L to 7.04 (0.61) mmol/L in
      patients receiving placebo, the total difference being statistically significant
      (P = 0.025). In the second trial ALE reduced total cholesterol levels by 18.5%
      from 7.74 mmol/L to 6.31 mmol/L after 42 +/- 3 days of treatment, whereas placebo
      reduced cholesterol by 8.6% from 7.69 mmol/L to 7.03 mmol/L (P = 0.00001). The
      third trial, which is available as abstract only and provides limited data,
      stated that ALE significantly reduced blood cholesterol compared with placebo in
      a subgroup of patients with baseline total cholesterol levels of more than 230
      mg/dL (P < 0.05). Trial reports indicate mild, transient and infrequent adverse
      events. AUTHORS' CONCLUSIONS: Data from three clinical trials assessing ALE for
      treating hypercholesterolaemia are available. Athough the trials are of adequate
      methodological quality they have some shortcomings and one is available as
      abstract only. There is an indication that ALE has potential in lowering
      cholesterol levels, but the evidence is, as yet, not convincing. The limited data
      on safety suggest only mild, transient and infrequent adverse events with the
      short term use of ALE.

PMID- 23543519
TI  - Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive
      fungal infection in very low birth weight infants.
AB  - BACKGROUND: Invasive fungal infection is an important cause of mortality and
      morbidity in very preterm or very low birth weight infants. Uncertainty exists
      about the effect of prophylactic oral/topical non-absorbed antifungals to reduce
      mucocutaneous colonisation and so limit the risk of invasive fungal infection in
      this population. OBJECTIVES: To assess the effect of prophylactic oral/topical
      non-absorbed antifungal therapy on the incidence of invasive fungal infection,
      mortality and morbidity in very preterm or very low birth weight infants. SEARCH
      METHODS: We used the standard search strategy of the Cochrane Neonatal Review
      Group. This included searches of the Cochrane Central Register of Controlled
      Trials (CENTRAL: The Cochrane Library, 2012, Issue 3), MEDLINE, EMBASE, and
      CINAHL (to August 2012), conference proceedings, and previous reviews. SELECTION
      CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that
      compared the effect of prophylactic oral/topical non-absorbed antifungal therapy
      versus placebo or no drug or another antifungal agent or dose regimen in very
      preterm or very low birth weight infants. DATA COLLECTION AND ANALYSIS: We
      extracted data using the standard methods of the Cochrane Neonatal Review Group
      with separate evaluation of trial quality and data extraction by two review
      authors. MAIN RESULTS: Four trials, in which a total of 1800 infants
      participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin
      or miconazole) with placebo or no drug. These trials had various methodological
      weaknesses including quasi-randomisation, lack of allocation concealment, and
      lack of blinding of intervention and outcomes assessment. The incidence of
      invasive fungal infection was very high in the control groups of three of these
      trials. Meta-analysis found a statistically significant reduction in the
      incidence of invasive fungal infection [typical risk ratio 0.20 (95% confidence
      interval 0.14 to 0.27); risk difference -0.18 (-0.21 to -0.16)] but substantial
      statistical heterogeneity was present. We did not find a statistically
      significant effect on mortality [typical risk ratio 0.87 (0.72 to 1.05); risk
      difference -0.03 (-0.06 to 0.01)]. None of the trials assessed posthospital
      discharge outcomes.Two trials (N = 265) assessed the effect of oral/topical non
      absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any
      statistically significant differences in the incidences of invasive fungal
      infection or all-cause mortality. AUTHORS' CONCLUSIONS: The finding of a
      reduction in risk of invasive fungal infection in very low birth weight infants
      treated with oral/topical non-absorbed antifungal prophylaxis should be
      interpreted cautiously because of methodological weaknesses in the included
      trials. Further large randomised controlled trials in current neonatal practice
      settings are needed to resolve this uncertainty. These trials might compare
      oral/topical non-absorbed antifungal agents with placebo, with each other, or
      with systemic antifungal agents and should include an assessment of effect on
      long-term neurodevelopmental outcomes.

PMID- 23543520
TI  - Infant position in neonates receiving mechanical ventilation.
AB  - BACKGROUND: A variety of body positions other than the standard supine position
      have been used in patients undergoing intensive care with hopes of reducing the
      incidence of pressure ulcers of the skin, contractures or ankylosis and improving
      the patients' well being. In patients from different age groups undergoing
      mechanical ventilation (MV) it has been observed that particular positions, such
      as the prone position, may improve some respiratory parameters. Benefits from
      these positions have not been clearly defined in critically ill newborns who may
      require mechanical ventilation for extended periods of time. OBJECTIVES: To
      assess the effects of different positioning of newborn infants receiving MV on
      short-term respiratory outcomes and complications of prematurity. SEARCH METHODS:
      Databases searched (up to December 2012) were the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 3), Oxford Database
      of Perinatal Trials, MEDLINE, CINAHL and EMBASE. Handsearches of proceedings of
      the Society for Pediatric Research from 1990 to July 2011 were used to identify
      unpublished studies. Clinicaltrials.gov was searched for any ongoing studies.
      SELECTION CRITERIA: Randomised or quasi-randomised clinical trials comparing
      different positions in newborns receiving mechanical ventilation. DATA COLLECTION
      AND ANALYSIS: Three independent and unblinded review authors assessed the trials
      for inclusion in the review and extracted the data. Data were double-checked and
      entered into the Review Manager software (RevMan). Risks of bias of the included
      studies were assessed using methods of randomisation and allocation concealment,
      completeness of follow-up and blinding of outcome measurements. MAIN RESULTS:
      Twelve trials involving 285 participants were included in this review. One of the
      included studies (N = 79) was not evaluated in the previous review. Several
      positions were compared: prone versus supine, prone versus lateral right, lateral
      right versus supine, lateral left versus supine, lateral alternant versus supine,
      lateral right versus lateral left, and good lung dependent versus good lung
      uppermost. Apart from one of the two studies that compared lateral right versus
      lateral left positions, one comparing lateral alternant versus supine, and one
      comparing prone versus the supine position, all the included studies had a
      crossover design. Comparing prone versus supine position, an increase in arterial
      oxygen tension (PO2) in the prone position of between 2.75 and 9.72 mm Hg (95%
      confidence interval (CI)) was observed (one trial). When % haemoglobin oxygen
      saturation was measured with pulse oximetry, the improvement in the prone
      position was from 1.18% to 4.36% (typical effect based on four trials). In
      addition, there was a slight improvement in the number of episodes of
      desaturation. It was not possible to establish whether this effect remained once
      the intervention was stopped. Negative effects from the interventions were not
      described, although these were not studied in sufficient detail. Effects of
      position on other outcomes were barely investigated. Only one study analysed
      tracheal cultures of neonates after five days of mechanical ventilation, finding
      lower bacterial colonization in the alternating l ateral position than in those
      neonates kept in the supine posture. Other effects, either positive or negative,
      cannot be excluded considering the small numbers of neonates that were studied.
      AUTHORS' CONCLUSIONS: The prone position was found to slightly improve the
      oxygenation in neonates undergoing mechanical ventilation. However, we found no
      evidence concerning whether particular body positions during the mechanical
      ventilation of the neonate are effective in producing sustained and clinically
      relevant improvements.

PMID- 23543521
TI  - Communication skills training for healthcare professionals working with people
      who have cancer.
AB  - BACKGROUND: This is an updated version of a review that was originally published
      in the Cochrane Database of Systematic Reviews in 2004, Issue 2. People with
      cancer, their families and carers have a high prevalence of psychological stress
      which may be minimised by effective communication and support from their
      attending healthcare professionals (HCPs). Research suggests communication skills
      do not reliably improve with experience, therefore, considerable effort is
      dedicated to courses that may improve communication skills for HCPs involved in
      cancer care. A variety of communication skills training (CST) courses have been
      proposed and are in practice. We conducted this review to determine whether CST
      works and which types of CST, if any, are the most effective. OBJECTIVES: To
      assess whether CST is effective in improving the communication skills of HCPs
      involved in cancer care, and in improving patient health status and satisfaction.
      SEARCH METHODS: We searched the following electronic databases: Cochrane Central
      Register of Controlled Trials (CENTRAL) Issue 2, 2012, MEDLINE, EMBASE, PsycInfo
      and CINAHL to February 2012. The original search was conducted in November 2001.
      In addition, we handsearched the reference lists of relevant articles and
      relevant conference proceedings for additional studies. SELECTION CRITERIA: The
      original review was a narrative review that included randomised controlled trials
      (RCTs) and controlled before-and-after studies. In this updated version, we
      limited our criteria to RCTs evaluating 'CST' compared with 'no CST' or other CST
      in HCPs working in cancer care. Primary outcomes were changes in HCP
      communication skills measured in interactions with real and/or simulated patients
      with cancer, using objective scales. We excluded studies whose focus was
      communication skills in encounters related to informed consent for research. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials and
      extracted data to a pre-designed data collection form. We pooled data using the
      random-effects model and, for continuous data, we used standardised mean
      differences (SMDs). MAIN RESULTS: We included 15 RCTs (42 records), conducted
      mainly in outpatient settings. Eleven studies compared CST with no CST
      intervention, three studies compared the effect of a follow-up CST intervention
      after initial CST training, and one study compared two types of CST. The types of
      CST courses evaluated in these trials were diverse. Study participants included
      oncologists (six studies), residents (one study) other doctors (one study),
      nurses (six studies) and a mixed team of HCPs (one study). Overall, 1147 HCPs
      participated (536 doctors, 522 nurses and 80 mixed HCPs).Ten studies contributed
      data to the meta-analyses. HCPs in the CST group were statistically significantly
      more likely to use open questions in the post-intervention interviews than the
      control group (five studies, 679 participant interviews; P = 0.04, I2 = 65%) and
      more likely to show empathy towards patients (six studies, 727 participant
      interviews; P = 0.004, I2 = 0%); we considered this evidence to be of moderate
      and high quality, respectively. Doctors and nurses did not perform statistically
      significantly differently for any HCP outcomes.There were no statistically
      significant differences in the other HCP communication skills except for the
      subgroup of participant interviews with simulated patients, where the
      intervention group was significantly less likely to present 'facts only' compared
      with the control group (four studies, 344 participant interviews; P = 0.01, I2 =
      70%).There were no significant differences between the groups with regard to
      outcomes assessing HCP 'burnout', patient satisfaction or patient perception of
      the HCPs communication skills. Patients in the control group experienced a
      greater reduction in mean anxiety scores in a meta-analyses of two studies (169
      participant interviews; P = 0.02; I2 = 8%); we considered this evidence to be of
      a very low quality. AUTHORS' CONCLUSIONS: Various CST courses appear to be
      effective in improving some types of HCP communication skills related to
      information gathering and supportive skills. We were unable to determine whether
      the effects of CST are sustained over time, whether consolidation sessions are
      necessary, and which types of CST programs are most likely to work. We found no
      evidence to support a beneficial effect of CST on HCP 'burnout', patients' mental
      or physical health, and patient satisfaction.

PMID- 23543522
TI  - WITHDRAWN: Immobilisation and functional treatment for acute lateral ankle
      ligament injuries in adults.
AB  - BACKGROUND: Acute lateral ankle ligament injuries (ankle sprains) are common
      problems in acute medical care. The treatment variation observed for the acutely
      injured lateral ankle ligament complex suggests a lack of evidence-based
      management strategies for this problem. OBJECTIVES: The objective of this review
      was to assess the effectiveness of methods of immobilisation for acute lateral
      ankle ligament injuries and to compare immobilisation with functional treatment
      methods. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group specialised register (December 2001); the Cochrane Controlled Trials
      Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966-May 2000), EMBASE
      (1988-May 2000), reference lists of articles, and contacted organisations and
      researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials comparing either different types of immobilisation or
      immobilisation versus functional treatments for injuries to the lateral ligament
      complex of the ankle in adults were included. Trials which investigated the
      treatment of chronic instability or post-surgical treatment were excluded. DATA
      COLLECTION AND ANALYSIS: Data were independently extracted by two authors. Where
      appropriate, results of comparable studies were pooled using fixed effects
      models. Individual and pooled statistics were reported as relative risks with 95%
      confidence intervals for dichotomous outcomes and weighted (WMD) or standardised
      (SMD) mean differences and 95% confidence intervals for continuous outcome
      measures. Heterogeneity between trials was tested using a standard chi-squared
      test. MAIN RESULTS: Twenty-one trials involving 2184 participants were included.
      The mean validity score of the included trials increased from 9.1 (SD 3.0) to 10
      (SD 2.9) after retrieving further information (maximum 18 points). Statistically
      significant differences in favour of functional treatment when compared with
      immobilisation were found for seven outcome measures: more patients returned to
      sport in the long term (relative risk (RR) 1.86, 95% confidence interval (CI)
      1.22 to 2.86); the time taken to return to sport was shorter (WMD 4.88 (days),
      95% CI 1.50 to 8.25); more patients had returned to work at short term follow-up
      (RR 5.75, 95% CI 1.01 to 32.71); the time taken to return to work was shorter
      (WMD 8.23 days, 95% CI 6.31 to 10.16); fewer patients suffered from persistent
      swelling at short term follow-up (RR 1.74, 95% CI 1.17 to 2.59); fewer patients
      suffered from objective instability as tested by stress X-ray (WMD 2.60, 95% CI
      1.24 to 3.96); and patients treated functionally were more satisfied with their
      treatment (RR 1.83, 95% CI 1.09 to 3.07). A separate analysis of trials that
      scored 50 per cent or more in quality assessment found a similar result for time
      to return to work only (WMD (days) 12.89, 95% CI 7.10 to 18.67). No significant
      differences between varying types of immobilisation, immobilisation and
      physiotherapy or no treatment were found, apart from one trial where patients
      returned to work sooner after treatment with a soft cast. In all analyses
      performed, no results were significantly in favour of immobilisation. AUTHORS'
      CONCLUSIONS: Functional treatment appears to be the favourable strategy for
      treating acute ankle sprains when compared with immobilisation. However, these
      results should be interpreted with caution, as most of the differences are not
      significant after exclusion of the low quality trials. Many trials were poorly
      reported and there was variety amongst the functional treatments evaluated.

PMID- 23543523
TI  - Operative caries management in adults and children.
AB  - BACKGROUND: The management of dental caries has traditionally involved removal of
      all soft demineralised dentine before a filling is placed. However, the benefits
      of complete caries removal have been questioned because of concerns about the
      possible adverse effects of removing all soft dentine from the tooth. Three
      groups of studies have also challenged the doctrine of complete caries removal by
      sealing caries into teeth using three different techniques. The first technique
      removes caries in stages over two visits some months apart, allowing the dental
      pulp time to lay down reparative dentine (the stepwise excavation technique). The
      second removes part of the dentinal caries and seals the residual caries into the
      tooth permanently (partial caries removal) and the third technique removes no
      dentinal caries prior to sealing or restoring (no dentinal caries removal). This
      is an update of a Cochrane review first published in 2006. OBJECTIVES: To assess
      the effects of stepwise, partial or no dentinal caries removal compared with
      complete caries removal for the management of dentinal caries in previously
      unrestored primary and permanent teeth. SEARCH METHODS: The following electronic
      databases were searched: the Cochrane Oral Health Group's Trials Register (to 12
      December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2012, Issue 11), MEDLINE via OVID (1946 to 12 December 2012) and
      EMBASE via OVID (1980 to 12 December 2012). There were no restrictions regarding
      language or date of publication. SELECTION CRITERIA: Parallel group and split
      mouth randomised and quasi-randomised controlled trials comparing stepwise,
      partial or no dentinal caries removal with complete caries removal, in unrestored
      primary and permanent teeth were included. DATA COLLECTION AND ANALYSIS: Three
      review authors extracted data independently and in triplicate and assessed risk
      of bias. Trial authors were contacted where possible for information. We used
      standard methodological procedures exacted by The Cochrane Collaboration. MAIN
      RESULTS: In this updated review, four new trials were included bringing the total
      to eight trials with 934 participants and 1372 teeth. There were three
      comparisons: stepwise caries removal compared to complete one stage caries
      removal (four trials); partial caries removal compared to complete caries removal
      (three trials) and no dentinal caries removal compared to complete caries removal
      (two trials). (One three-arm trial compared complete caries removal to both
      stepwise and partial caries removal.) Four studies investigated primary teeth,
      three permanent teeth and one included both. All of the trials were assessed at
      high risk of bias, although the new trials showed evidence of attempts to
      minimise bias.Stepwise caries removal resulted in a 56% reduction in incidence of
      pulp exposure (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.33 to 0.60, P
      < 0.00001, I(2) = 0%) compared to complete caries removal based on moderate
      quality evidence, with no heterogeneity. In these four studies, the mean
      incidence of pulp exposure was 34.7% in the complete caries removal group and
      15.4% in the stepwise groups. There was also moderate quality evidence of no
      difference in the outcome of signs and symptoms of pulp disease (RR 0.78, 95% CI
      0.39 to 1.58, P = 0.50, I(2) = 0%).Partial caries removal reduced incidence of
      pulp exposure by 77% compared to complete caries removal (RR 0.23, 95% CI 0.08 to
      0.69, P = 0.009, I(2) = 0%), also based on moderate quality evidence with no
      evidence of heterogeneity. In these two studies the mean incidence of pulp
      exposure was 21.9% in the complete caries removal groups and 5% in the partial
      caries removal groups. There was insufficient evidence to determine whether or
      not there was a difference in signs and symptoms of pulp disease (RR 0.27, 95% CI
      0.05 to 1.60, P = 0.15, I(2) = 0%, low quality evidence), or restoration failure
      (one study showing no difference and another study showing no failures in either
      group, very low quality evidence).No dentinal caries removal was compared to
      complete caries removal in two very different studies. There was some moderate
      evidence of no difference between these techniques for the outcome of signs and
      symptoms of pulp disease and reduced risk of restoration failure favouring no
      dentinal caries removal, from one study, and no instances of pulp disease or
      restoration failure in either group from a second quasi-randomised study. Meta
      analysis of these two studies was not performed due to substantial clinical
      differences between the studies. AUTHORS' CONCLUSIONS: Stepwise and partial
      excavation reduced the incidence of pulp exposure in symptomless, vital, carious
      primary as well as permanent teeth. Therefore these techniques show clinical
      advantage over complete caries removal in the management of dentinal caries.
      There was no evidence of a difference in signs or symptoms of pulpal disease
      between stepwise excavation, and complete caries removal, and insufficient
      evidence to determine whether or not there was a difference in signs and symptoms
      of pulp disease between partial caries removal and complete caries removal. When
      partial caries removal was carried out there was also insufficient evidence to
      determine whether or not there is a difference in risk of restoration failure.
      The no dentinal caries removal studies investigating permanent teeth had a
      similar result with no difference in restoration failure. The other no dentinal
      caries removal study, which investigated primary teeth, showed a statistically
      significant difference in restoration failure favouring the intervention.Due to
      the short term follow-up in most of the included studies and the high risk of
      bias, further high quality, long term clinical trials are still required to
      assess the most effective intervention. However, it should be noted that in
      studies of this nature, complete elimination of risk of bias may not necessarily
      be possible. Future research should also investigate patient centred outcomes.

PMID- 23543524
TI  - Ginkgo biloba for tinnitus.
AB  - BACKGROUND: This is an update of a Cochrane review first published in The
      Cochrane Library in Issue 2, 2004 and previously updated in 2007 and
      2009.Tinnitus can be described as the perception of sound in the absence of
      external acoustic stimulation. At present no specific therapy for tinnitus is
      acknowledged to be satisfactory in all patients. There are a number of reports in
      the literature suggesting that Ginkgo biloba may be effective in the management
      of tinnitus. However, there also appears to be a strong placebo effect in
      tinnitus management. OBJECTIVES: To assess the effect of Ginkgo biloba in
      patients who are troubled by tinnitus. SEARCH METHODS: We searched the Cochrane
      Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central
      Register of Controlled Trials (CENTRAL); PubMed; EMBASE; AMED; 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 12 March
      2012. SELECTION CRITERIA: Adults (18 years and over) complaining of tinnitus or
      adults with a primary complaint of cerebral insufficiency, where tinnitus forms
      part of the syndrome. DATA COLLECTION AND ANALYSIS: Both original authors
      independently extracted data and assessed trials for quality. For the 2012 update
      two authors determined trial eligibility, extracted data, analysed data and
      updated the contents of the review. MAIN RESULTS: Four trials with a total of
      1543 participants were included in the review; we assessed all the included
      studies as having a low risk of bias. Three trials (1143 participants) included
      patients with a primary complaint of tinnitus and one (400 participants) included
      patients with mild to moderate dementia, some of whom had tinnitus.There was no
      evidence that Gingko biloba was effective in patients with a primary complaint of
      tinnitus. In the study of patients with dementia, mean baseline levels of
      tinnitus were low (1.7 to 2.5 on a 10-point subjective symptom rating scale). A
      small but statistically significant reduction of 1.5 and 0.7 points was seen in
      patients taking Gingko biloba with vascular dementia and Alzheimer's disease
      respectively. The practical clinical significance of this is unclear. The
      incidence of side effects was low. AUTHORS' CONCLUSIONS: The limited evidence
      does not demonstrate that Ginkgo biloba is effective for tinnitus when this is
      the primary complaint.

PMID- 23543525
TI  - Interventions for replacing missing teeth: different times for loading dental
      implants.
AB  - BACKGROUND: To minimise the risk of implant failures after their placement,
      dental implants are kept load-free for 3 to 8 months to establish
      osseointegration (conventional loading). It would be beneficial if the healing
      period could be shortened without jeopardising implant success. Nowadays implants
      are loaded early and even immediately and it would be useful to know whether
      there is a difference in success rates between immediately and early loaded
      implants compared with conventionally loaded implants. OBJECTIVES: To evaluate
      the effects of (1) immediate (within 1 week), early (between 1 week and 2
      months), and conventional (after 2 months) loading of osseointegrated implants;
      (2) immediate occlusal versus non-occlusal loading and early occlusal versus non
      occlusal loading; (3) direct loading versus progressive loading immediately,
      early and conventionally. SEARCH METHODS: The following electronic databases were
      searched: the Cochrane Oral Health Group's Trials Register (to 8 June 2012), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,
      2012, Issue 4), MEDLINE via OVID (1946 to 8 June 2012) and EMBASE via OVID (1980
      to 8 June 2012). Authors of identified trials were contacted to find unpublished
      randomised controlled trials (RCTs). There were no restrictions regarding
      language or date of publication. SELECTION CRITERIA: All RCTs of root-form
      osseointegrated dental implants, having a follow-up of 4 months to 1 year,
      comparing the same implant type immediately, early or conventionally loaded,
      occlusally or non-occlusally loaded, or progressively loaded or not. Outcome
      measures were: prosthesis and implant failures and radiographic marginal bone
      level changes. DATA COLLECTION AND ANALYSIS: Data were independently extracted,
      in duplicate, by at least two review authors. Trial authors were contacted for
      missing information. Risk of bias was assessed for each trial by at least two
      review authors, and data were extracted independently, and in duplicate. Results
      were combined using fixed-effect models with mean differences (MD) for continuous
      outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence
      intervals (CI). A summary of findings table of the main findings was constructed.
      MAIN RESULTS: Forty-five RCTs were identified and, from these, 26 trials
      including a total of 1217 participants and 2120 implants were included. Three
      trials were at low risk of bias, 12 were at high risk of bias and for the
      remaining 11 the risk of bias was unclear. In nine of the included studies there
      were no prosthetic failures within the first year, with no implant failures in 7
      studies and the mean rate of implant failure in all 26 trials was a low 2.5%.
      From 15 RCTs comparing immediate with convential loading there was no evidence of
      a difference in either prosthesis failure (RR 1.87; 95% CI 0.70 to 5.01; 8
      trials) or implant failure (RR 1.65; 95% CI 0.68 to 3.98; 10 trials) in the first
      year, but there is some evidence of a small reduction in bone loss favouring
      immediate loading (MD -0.10 mm; 95% CI -0.20 to -0.01; P = 0.03; 9 trials), with
      some heterogeneity (Tau2 = 0.01; Chi2 = 14.37, df = 8 (P = 0.07); I2 = 44%).
      However, this very small difference may not be clinically important. From three
      RCTs which compared early loading with conventional loading, there is
      insufficient evidence to determine whether or not there is a clinically important
      difference in prosthesis failure, implant failure or bone loss. Six RCTs compared
      immediate and early loading and found insufficient evidence to determine whether
      or not there is a clinically important difference in prosthesis failure, implant
      failure or bone loss. From the two trials which compared occlusal loading with
      non-occlusal loading there is insufficient evidence to determine whether there is
      a clinically important difference in the outcomes of prosthesis failure, implant
      failure or bone loss. We did not identify any trials which evaluated progressive
      loading of implants. AUTHORS' CONCLUSIONS: Overall there was no convincing
      evidence of a clinically important difference in prosthesis failure, implant
      failure, or bone loss associated with different loading times of implants. More
      well-designed RCTs are needed and should be reported according to the CONSORT
      guidelines (www.consort-statement.org/).

PMID- 23543526
TI  - Preoperative skin antiseptics for preventing surgical wound infections after
      clean surgery.
AB  - BACKGROUND: Surgical site infection rates in the month following clean surgery
      vary from 0.6% (knee prosthesis) to 5% (limb amputation). Due to the large number
      of clean surgical procedures conducted annually the costs of these surgical site
      infections (SSIs) can be considerable in financial and social terms. Preoperative
      skin antisepsis using antiseptics is performed to reduce the risk of SSIs by
      removing soil and transient organisms from the skin where a surgical incision
      will be made. Antiseptics are thought to be toxic to bacteria and therefore aid
      their mechanical removal. The effectiveness of preoperative skin preparation is
      thought to be dependent on both the antiseptic used and the method of
      application, however, it is unclear whether preoperative skin antisepsis actually
      reduces postoperative wound infection, and, if so, which antiseptic is most
      effective. OBJECTIVES: To determine whether preoperative skin antisepsis
      immediately prior to surgical incision for clean surgery prevents SSI and to
      determine the comparative effectiveness of alternative antiseptics. SEARCH
      METHODS: For this second update we searched the The Cochrane Wounds Group
      Specialised Register (searched 7 August 2012), The Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE 
      (1950 to July Week 4 2012), Ovid MEDLINE (In-Process & Other Non-Indexed
      Citations August 06, 2012), Ovid EMBASE (1980 to 2012 Week 31), EBSCO CINAHL
      (2007 to 3 August 2012). SELECTION CRITERIA: Randomised controlled trials
      evaluating the use of preoperative skin antiseptics applied immediately prior to
      incision in clean surgery. There was no restriction on the inclusion of reports
      based on language of publication, date or publication status. DATA COLLECTION AND
      ANALYSIS: Data extraction and assessment of risk of bias were undertaken
      independently by two review authors. MAIN RESULTS: Thirteen studies were included
      in this review (2,623 participants). These evaluated several different types of
      skin antiseptics - leading to 11 different comparisons being made. Although the
      antiseptics evaluated differed between studies, all trials involved some form of
      iodine. Iodine in alcohol was compared to alcohol alone in one trial; one trial
      compared povidone iodine paint (solution type not reported) with soap and
      alcohol. Six studies compared different types of iodine-containing products with
      each other and five compared iodine-containing products with chlorhexidine
      containing products.There was evidence from one study suggesting that
      preoperative skin preparation with 0.5% chlorhexidine in methylated spirits led
      to a reduced risk of SSI compared with an alcohol based povidone iodine solution:
      RR 0.47 (95% CI 0.27 to 0.82). However, it is important to note that the trial
      does not report important details regarding the interventions (such as the
      concentration of povidone iodine paint used) and trial conduct, such that risk of
      bias was unclear.There were no other statistically significant differences in SSI
      rates in the other comparisons of skin antisepsis. Overall the risk of bias in
      included studies was unclear.A mixed treatment comparison meta-analysis was
      conducted and this suggested that alcohol-containing products had the highest
      probability of being effective - however, again the quality of this evidence was
      low. AUTHORS' CONCLUSIONS: A comprehensive review of current evidence found some
      evidence that preoperative skin preparation with 0.5% chlorhexidine in methylated
      spirits was associated with lower rates of SSIs following clean surgery than
      alcohol-based povidone iodine paint. However this single study was poorly
      reported. Practitioners may therefore elect to consider other characteristics
      such as costs and potential side effects when choosing between alternatives.The
      design of future trials should be driven by the questions of high priority to
      decision makers. It may be that investment in at least one large trial (in terms
      of participants) is warranted in order to add definitive and hopefully conclusive
      data to the current evidence base. Ideally any future trial would evaluate the
      iodine-containing and chlorhexidine-containing solutions relevant to current
      practice as well as the type of solution used (alcohol vs. aqueous).

PMID- 23543527
TI  - Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic
      patent ductus arteriosus in preterm infants.
AB  - BACKGROUND: A patent ductus arteriosus (PDA) with significant left to right shunt
      increases morbidity and mortality in preterm infants. Early closure of the ductus
      arteriosus may be achieved pharmacologically or by surgery. The preferred initial
      treatment of a symptomatic PDA, surgical ligation or treatment with indomethacin,
      is not clear. OBJECTIVES: To compare the effect of surgical ligation of PDA
      versus medical treatment with cyclooxygenase inhibitors (indomethacin, ibuprofen
      or mefenamic acid), each used as the initial treatment, on neonatal mortality in
      preterm infants with a symptomatic PDA. SEARCH METHODS: For this update we
      searched The Cochrane Library 2012, Issue 2, MEDLINE, EMBASE, CINAHL,
      Clinicaltrials.gov, Controlled-trials.com, Proceedings of the Annual Meetings of
      the Pediatric Academic Societies (2000 to 2011) (Abstracts2View(TM)) and Web of
      Science on 8 February 2012. SELECTION CRITERIA: Randomised or quasi-randomised
      trials in preterm or low birth weight neonates with symptomatic PDA and comparing
      surgical ligation with medical treatment with cyclooxygenase inhibitors, each
      used as the initial treatment for closure of PDA. DATA COLLECTION AND ANALYSIS:
      The authors independently assessed methodological quality and extracted data for
      the included trial. We used RevMan 5.1 for analyses of the data. MAIN RESULTS:
      One study reporting on 154 neonates was found eligible. No significant difference
      between surgical closure and indomethacin treatment was found for in-hospital
      mortality, chronic lung disease, necrotising enterocolitis, sepsis, creatinine
      level or intraventricular haemorrhage. There was a significant increase in the
      surgical group in the incidence of pneumothorax (risk ratio (RR) 2.68; 95%
      confidence interval (CI) 1.45 to 4.93; risk difference (RD) 0.25; 95% CI 0.11 to
      0.38; number needed to treat to harm (NNTH) 4 (95% CI 3 to 9)) and retinopathy of
      prematurity stage III and IV (RR 3.80; 95% CI 1.12 to 12.93; RD 0.11; 95% CI 0.02
      to 0.20; NNTH 9 (95% CI 5 to 50)) compared to the indomethacin group. There was a
      statistically significant decrease in failure of ductal closure rate in the
      surgical group as compared to the indomethacin group (RR 0.04; 95% CI 0.01 to
      0.27; RD -0.32; 95% CI -0.43 to -0.21, number needed to treat to benefit (NNTB) 3
      (95% CI 2 to 4)). No new trials were identified for inclusion in the 2012 update.
      AUTHORS' CONCLUSIONS: There are insufficient data to conclude whether surgical
      ligation or medical treatment with indomethacin is preferred as the initial
      treatment for symptomatic PDA in preterm infants.

PMID- 23543528
TI  - Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type
      1 and 2.
AB  - BACKGROUND: Adequate contraceptive advice is important in both women with
      diabetes mellitus type 1 and type 2 to reduce the risk of maternal and infant
      morbidity and mortality in unplanned pregnancies. A wide variety of
      contraceptives are available for these women. However, hormonal contraceptives
      might influence carbohydrate and lipid metabolism and increase micro- and
      macrovascular complications, so caution in selecting a contraceptive method is
      required. OBJECTIVES: To investigate whether progestogen-only, combined estrogen
      and progestogen or non-hormonal contraceptives differ in terms of effectiveness
      in preventing pregnancy, in their side effects on carbohydrate and lipid
      metabolism, and in long-term complications such as micro- and macrovascular
      disease when used in women with diabetes mellitus. SEARCH METHODS: The search was
      performed in CENTRAL, MEDLINE, EMBASE, POPLINE, CINAHL, WorldCat, ECO,
      ArticleFirst, the Science Citation Index, the British Library Inside, and
      reference lists of relevant articles. The last search was performed in January
      2013. In addition, experts in the field and pharmaceutical companies marketing
      contraceptives were contacted to identify published, unpublished or ongoing
      studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials
      that studied women with diabetes mellitus comparing: 1. hormonal versus non
      hormonal contraceptives; 2. progestogen-only versus estrogen and progestogen
      contraceptives; 3. contraceptives containing < 50 ug estrogen versus
      contraceptives containing >= 50 ug estrogen; and 4. contraceptives containing
      first-, second- and third-generation progestogens, drospirenone and cyproterone
      acetate. The principal outcomes were contraceptive effectiveness, diabetes
      control, lipid metabolism and micro- and macrovascular complications. DATA
      COLLECTION AND ANALYSIS: Two investigators evaluated the titles and abstracts
      identified from the literature search. Quality assessment was performed
      independently with discrepancies resolved by discussion or consulting a third
      review author. Because the trials differed in studied contraceptives, participant
      characteristics and methodological quality, we could not combine the data in a
      meta-analysis. The trials were therefore examined on an individual basis and
      narrative summaries were provided. MAIN RESULTS: Four randomised controlled
      trials were included. No unintended pregnancies were reported during the study
      periods. Only one trial was of good methodological quality. It compared the
      influence of a levonorgestrel-releasing intrauterine device (IUD) versus a copper
      IUD on carbohydrate metabolism in women with type 1 diabetes mellitus. No
      significant difference was found between the two groups. The other three trials
      were of limited methodological quality. Two compared progestogen-only pills with
      different estrogen and progestogen combinations, and one also included the
      levonorgestrel-releasing IUD and copper IUD. The trials reported that blood
      glucose levels remained stable during treatment with most regimens. Only high
      dose combined oral contraceptives and 30 ug ethinylestradiol + 75 ug gestodene
      were identified as slightly impairing glucose homeostasis. The three studies
      found conflicting results regarding lipid metabolism. Some combined oral
      contraceptives appeared to have a minor adverse effect while others appeared to
      slightly improve lipid metabolism. The copper IUD and progestogen-only oral
      contraceptives also slightly improved lipid metabolism and no influence was seen
      while using the levonorgestel-releasing IUD. Only one study reported on micro-
      and macrovascular complications. It observed no signs or symptoms of
      thromboembolic incidents or visual disturbances, however study duration was
      short. Only minor adverse effects were reported in two studies. AUTHORS'
      CONCLUSIONS: The four included randomised controlled trials in this systematic
      review provided insufficient evidence to assess whether progestogen-only and
      combined contraceptives differ from non-hormonal contraceptives in diabetes
      control, lipid metabolism and complications. Three of the four studies were of
      limited methodological quality, sponsored by pharmaceutical companies and
      described surrogate outcomes. Ideally, an adequately reported, high-quality
      randomised controlled trial analysing both intermediate outcomes (that is glucose
      and lipid metabolism) and true clinical endpoints (micro- and macrovascular
      disease) in users of combined, progestogen-only and non-hormonal contraceptives
      should be conducted. However, due to the low incidence of micro- and
      macrovascular disease and accordingly the large sample size and long follow-up
      period needed to observe differences in risk, a randomised controlled trial might
      not be the ideal design.

PMID- 23543529
TI  - WITHDRAWN: Patient controlled intravenous opioid analgesia versus continuous
      epidural analgesia for pain after intra-abdominal surgery.
AB  - BACKGROUND: There are two common techniques for postoperative pain control after
      intra-abdominal surgery: patient-controlled analgesia (PCA) with intravenous
      opioids and continuous epidural analgesia (CEA). It is uncertain which method has
      better pain control and fewer adverse effects. OBJECTIVES: The objective of this
      review was to compare PCA opioid therapy with CEA for pain control after intra
      abdominal surgery in terms of analgesic efficacy, side effects, patient
      satisfaction and surgical outcome by meta-analysis of the relevant trials. SEARCH
      METHODS: We searched CENTRAL (The Cochrane Library Issue 4, 2002), MEDLINE
      (January 1966 to October 2002), EMBASE (January 1988 to October 2002), and
      reference lists of articles. We also contacted researchers in the field.
      SELECTION CRITERIA: Randomized controlled trials of adult patients after intra
      abdominal surgery comparing the effect of two pain control regimens in terms of
      analgesic efficacy and side effects. In the patient-controlled analgesia (PCA)
      group the patient should be able to operate the device himself. In the continuous
      epidural analgesia group there was no PCA device. DATA COLLECTION AND ANALYSIS:
      Two authors independently assessed trial quality and extracted data. Study
      authors were contacted for additional information. Adverse effects information
      was collected from the trials. MAIN RESULTS: Nine studies involving 711
      participants were included. The PCA group had a higher pain visual analogue scale
      than the CEA group during 6, 24 and 72 hour periods. The weighted mean difference
      and 95% confidence interval of resting pain was 1.74 (95% CI 1.30 to 2.19), 0.99
      (95% CI 0.65 to 1.33), and 0.63 (95% CI 0.24 to 1.01), respectively. The length
      of hospital stay and other adverse effects were not statistically different
      except that the incidence of pruritus was lower in the PCA group, odds ratio of
      0.27 (95% CI 0.11 to 0.64). AUTHORS' CONCLUSIONS: CEA is superior to opioid PCA
      in relieving postoperative pain for up to 72 hours in patients undergoing intra
      abdominal surgery, but it is associated with a higher incidence of pruritus.
      There is insufficient evidence to draw comparisons about the other advantages and
      disadvantages of these two methods of pain relief.

PMID- 23543530
TI  - Megestrol acetate for treatment of anorexia-cachexia syndrome.
AB  - BACKGROUND: This is an updated version of a previously published review in The
      Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of
      anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve
      appetite and to increase weight in cancer-associated anorexia. In 1993, MA was
      approved by the US Food and Drug Administration for the treatment of anorexia,
      cachexia or unexplained weight loss in patients with AIDS. The mechanism by which
      MA increases appetite is unknown and its effectiveness for anorexia and cachexia
      in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under
      investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of
      MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and
      other underlying pathologies. SEARCH METHODS: We sought studies through an
      extensive search of electronic databases, journals, reference lists, contact with
      investigators and other search strategies outlined in the methods. The most
      recent search for this update was carried out in May 2012. SELECTION CRITERIA:
      Studies were included in the review if they assessed MA compared to placebo or
      other drug treatments in randomised controlled trials of patients with a clinical
      diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other
      underlying pathology. DATA COLLECTION AND ANALYSIS: Two independent review
      authors conducted data extraction and evaluated methodological quality. We
      performed quantitative analyses using appetite and quality of life as a
      dichotomous variable, and analysed weight gain as continuous and dichotomous
      variables. MAIN RESULTS: We included 35 trials in this update, the same number
      but not the same trials as in the previous version of the review. The trials
      comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials
      compared MA at different doses with placebo, seven trials compared different
      doses of MA with other drug treatments and 10 trials compared different doses of
      MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with
      regard to appetite improvement and weight gain in cancer, AIDS and other
      underlying conditions, and lack of benefit in the same patients when MA was
      compared to other drugs. There was insufficient information to define the optimal
      dose of MA, but higher doses were more related to weight improvement than lower
      doses. Quality of life improvement in patients was seen only when comparing MA
      versus placebo but not other drugs in both subcategories: cancer and AIDS.
      Oedema, thromboembolic phenomena and deaths were more frequent in the patients
      treated with MA. More than 40 side effects were studied. AUTHORS' CONCLUSIONS:
      This review shows that MA improves appetite and is associated with slight weight
      gain in cancer, AIDS and in patients with other underlying pathology. Despite the
      fact that these patients are receiving palliative care they should be informed of
      the risks involved in taking MA.

PMID- 23543531
TI  - Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease.
AB  - BACKGROUND: Amyotrophic lateral sclerosis, also known as motor neuron disease, is
      a fatal neurodegenerative disease. Neuromuscular respiratory failure is the
      commonest cause of death, usually within two to five years of the disease onset.
      Supporting respiratory function with mechanical ventilation may improve survival
      and quality of life. This is the first update of a review first published in
      2009. OBJECTIVES: The primary objective of the review is to examine the efficacy
      of mechanical ventilation (tracheostomy and non-invasive ventilation) in
      improving survival in ALS. The secondary objectives are to examine the effect of
      mechanical ventilation on functional measures of disease progression and quality
      of life in people with ALS; and assess adverse events related to the
      intervention. SEARCH METHODS: We searched The Cochrane Neuromuscular Disease
      Group Specialized Register (1 May 2012), CENTRAL (2012, Issue 4), MEDLINE
      (January 1966 to April 2012), EMBASE (January 1980 to April 2012), CINAHL Plus
      (January 1937 to April 2012), and AMED (January 1985 to April 2012). We also
      searched for ongoing studies on ClinicalTrials.gov. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials involving non-invasive or
      tracheostomy assisted ventilation in participants with a clinical diagnosis of
      amyotrophic lateral sclerosis, independent of the reported outcomes. We planned
      to include comparisons with no intervention or the best standard care. DATA
      COLLECTION AND ANALYSIS: For the original review, four authors independently
      selected studies for assessment and two authors reviewed searches for this
      update. All authors extracted data independently from the full text of selected
      studies and assessed the risk of bias in studies that met the inclusion criteria.
      We attempted to obtain missing data where possible. We planned to collect adverse
      event data from included studies. MAIN RESULTS: For the original Cochrane review,
      the review authors identified and included two randomised controlled trials
      involving 54 participants with ALS receiving non-invasive ventilation. There were
      no new randomised or quasi-randomised controlled trials at this first
      update.Incomplete data were published for one study and we contacted the trial
      authors who were not able to provide the missing data. Therefore, the results of
      the review were based on a single study of 41 participants that compared non
      invasive ventilation with standard care. It was a well conducted study with low
      risk of bias.The study showed that the overall median survival was significantly
      different between the group treated with non-invasive ventilation and the
      standard care group. The median survival in the non-invasive ventilation group
      was 48 days longer (219 days compared to 171 days for the standard care group
      (estimated 95% CI 12 to 91 days, P = 0.0062)). This survival benefit was
      accompanied by an enhanced quality of life. On subgroup analysis, the survival
      and quality of life benefit was much more in the subgroup with normal to
      moderately impaired bulbar function (20 participants); median survival was 205
      days longer (216 days in NIV group versus 11 days in the standard care group, P =
      0.0059). Non-invasive ventilation did not prolong survival in participants with
      poor bulbar function (21 participants), although it showed significant
      improvement in the mean symptoms domain of the Sleep Apnoea Quality of Life Index
      but not in the Short Form-36 Health Survey Mental Component Summary score.
      Neither trial reported clinical data on intervention related adverse effects.
      AUTHORS' CONCLUSIONS: Evidence from a single randomised trial of non-invasive
      ventilation in 41 participants suggests that it significantly prolongs survival
      and improves or maintains quality of life in people with ALS. Survival and some
      measures of quality of life were significantly improved in the subgroup of people
      with better bulbar function, but not in those with severe bulbar impairment.
      Future studies should examine the health economics of NIV and factors influencing
      access to NIV. We need to understand the factors, personal and socioeconomic,
      that determine access to NIV.

PMID- 23543532
TI  - Antibiotics for brain abscesses in people with cyanotic congenital heart disease.
AB  - BACKGROUND: Brain abscess is a focal, intracerebral infection that begins as a
      localized area of brain infection and develops into a collection of pus
      surrounded by a well-vascularized capsule. People with cyanotic congenital heart
      disease are at risk of developing brain abscess. OBJECTIVES: To evaluate the
      effectiveness of antibiotic regimens for treating brain abscess in people with
      cyanotic congenital heart disease. SEARCH METHODS: We updated the searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library
      Issue 12 of 12, December 2012, MEDLINE Ovid (1946 to December Week 4 2012),
      EMBASE Ovid (1980 to 2013 Week 01) and LILACS (1980 to 9 January 2013) on 9
      January 2013. No language or publication restrictions were applied. SELECTION
      CRITERIA: Randomized controlled trials that reported clinically meaningful
      outcomes and presented results on an intention to treat basis, irrespective of
      blinding, publication status, or language. DATA COLLECTION AND ANALYSIS: Data
      were to be extracted, unblinded, by the two reviewers independently. MAIN
      RESULTS: No studies meeting the inclusion criteria were identified. AUTHORS'
      CONCLUSIONS: There are no randomized controlled trials about the effectiveness of
      antibiotic regimens for treating people with cyanotic congenital heart disease
      who developed a brain abscess. Currently, the antibiotic regimens used are based
      on previous retrospective studies and clinical experience. There is a need for a
      well designed multicentre randomized controlled trial to evaluate the effects of
      different antibiotic regimens.

PMID- 23543533
TI  - Chinese medicinal herbs for influenza.
AB  - BACKGROUND: Influenza is a communicable acute respiratory infection which, during
      epidemics, can cause high morbidity and mortality rates. Traditional Chinese
      medicinal herbs, often administered following a particular Chinese medical
      theory, may be a potential treatment of choice. OBJECTIVES: To assess the effect
      of Chinese medicinal herbs used to prevent and treat influenza and to estimate
      the frequency of adverse effects. SEARCH METHODS: We searched CENTRAL (2012,
      Issue 11), MEDLINE (January 1966 to November week 2, 2012), EMBASE (January 1988
      to November 2012) and CNKI (January 1988 to 29 March 2012). We also searched
      reference lists of articles and the WHO ICTRP search portal (November 2012).
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing traditional
      Chinese medicinal herbs with placebo, no treatment or conventional medicine
      normally used in preventing and treating uncomplicated influenza. DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data and assessed trial
      quality. MAIN RESULTS: We included 18 studies involving 2521 participants. The
      methodological quality of 17 included studies was poor. Included RCTs separately
      compared medicinal herbs with different antiviral drugs, precluding any pooling
      of results. Only three indicated that compared with antiviral drugs, Chinese
      medicinal herbs may be effective in preventing influenza and alleviating
      influenza symptoms. 'Ganmao' capsules were found to be more effective than
      amantadine in decreasing influenza symptoms and speeding recovery in one study
      (in which adverse reactions were mentioned in the amantadine group although no
      data were reported). There were no significant differences between 'E Shu You'
      and ribavirin in treating influenza, nor in the occurrence of adverse reactions.
      Ten studies reported mild adverse reactions. AUTHORS' CONCLUSIONS: Most Chinese
      medical herbs in the included studies showed similar effects to antiviral drugs
      in preventing or treating influenza. Few were shown to be superior to antiviral
      drugs. No obvious adverse events were reported in the included studies. However,
      current evidence remains weak due to methodological limitations of the trials.
      More high-quality RCTs with larger numbers of participants and clear reporting
      are needed.

PMID- 23543534
TI  - WITHDRAWN: Interventions for treating wrist fractures in children.
AB  - BACKGROUND: Approximately a third of all fractures in children occur at the
      wrist, usually from falling onto an outstretched hand. OBJECTIVES: We aimed to
      evaluate removable splintage versus plaster casts (requiring removal by a
      specialist) for undisplaced compression (buckle) fractures; cast length and
      position; and the role of surgical fixation for displaced wrist fractures in
      children. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group Specialised Register (October 2007), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2007, Issue 4), MEDLINE (from 1966),
      EMBASE (from 1988), CINAHL (from 1982) and reference lists of articles. Date of
      last search October 2007. SELECTION CRITERIA: Any randomised or quasi-randomised
      controlled trials comparing types and position of casts and the use of surgical
      fixation for distal radius fractures in children. DATA COLLECTION AND ANALYSIS:
      Two authors performed trial selection. All three authors independently assessed
      methodological quality and extracted data. MAIN RESULTS: The 10 included trials,
      involving 827 children, were of variable quality.Four trials compared removable
      splintage versus the traditional below-elbow cast in children with buckle
      fractures. There was no short-term deformity recorded in all four trials and, in
      one trial, no refracture at six months. The Futura splint was cheaper to use; a
      removable plaster splint was less restrictive to wear enabling more children to
      bathe and participate in other activities, and the option preferred by children
      and parents; the soft bandage was more comfortable, convenient and less painful
      to wear; home-removable plaster casts removed by parents did not result in
      significant differences in outcome but were strongly favoured by parents.Two
      trials found below-elbow versus above-elbow casts did not increase redisplacement
      of reduced fractures or cast-related complications, were less restrictive during
      use and avoided elbow stiffness.One trial evaluating the effect of arm position
      in above-elbow casts found no effect on deformity.Three trials found that
      percutaneous wiring significantly reduced redisplacement and remanipulation but
      one of these found no advantage in function at three months. AUTHORS'
      CONCLUSIONS: Limited evidence supports the use of removable splintage for buckle
      fractures and challenges the traditional use of above-elbow casts after reduction
      of displaced fractures. Although percutaneous wire fixation prevents
      redisplacement, the effects on longer term outcomes including function are not
      established.Further research is warranted on the optimum approach, including
      splintage, for buckle fractures; and on the use of below-elbow casts and
      indications for surgery for displaced wrist fractures in children.

PMID- 23543535
TI  - Lactase treated feeds to promote growth and feeding tolerance in preterm infants.
AB  - BACKGROUND: Successful transition from parenteral nutrition to full enteral
      feedings during the immediate neonatal period is associated with improved growth
      in preterm infants. Lactase is the last of the major intestinal disaccharidases
      to develop in preterm infants. Because of inadequate lactase activity, preterm
      infants are unable to digest lactose. Lactase preparations could potentially be
      used to hydrolyse lactose in formulas and breast milk to minimize lactose
      malabsorption in preterm infants. OBJECTIVES: To assess the effectiveness and
      safety of the addition of lactase to milk compared to placebo or no intervention
      for the promotion of growth and feeding tolerance in preterm infants. PRIMARY
      OUTCOMES: weight gain expressed as grams/kg/day, growth expressed as weight,
      length and head circumference percentile for postmenstrual age (PMA), assessed at
      birth and at 40 weeks PMA, days to achieve full enteral feeds. SECONDARY
      OUTCOMES: several common outcomes associated with preterm birth, and adverse
      effects. SEARCH METHODS: Electronic and manual searches were conducted in January
      2005 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library, 2004, Issue 4), MEDLINE (1966 to Jan 2005), EMBASE (1980 to Jan 2005)
      and CINAHL (1982 to Jan 2005), personal files, bibliographies of identified
      trials and abstracts by the Pediatric Academic Societies' Meetings and the
      European Society of Pediatric Research Meetings published in Pediatric Research.
      The searches were repeated in May 2012 of The Cochrane Library, MEDLINE, EMBASE
      and CINAHL and abstracts from the Pediatric Academic Societies' Annual Meetings
      from 2000 to 2012 (Abstracts2View). The Web of Science was searched using the
      only previously identified trial by Erasmus 2002 as the starting point to search
      for additional trials that cited this trial. SELECTION CRITERIA: Types of
      studies: randomized or quasi-randomized controlled trials. PARTICIPANTS: preterm
      infants < 37 weeks PMA. INTERVENTION: addition of lactase to milk versus placebo
      or no intervention. DATA COLLECTION AND ANALYSIS: The standard methods of the
      Cochrane Neonatal Review Group were followed independently by the review authors
      to assess study quality and report outcomes. Treatment effects, calculated using
      Review Manager 5, included risk ratio (RR), risk difference (RD) and mean
      difference (MD), all with 95% confidence intervals (CI). A fixed-effect model was
      used for meta-analyses. We did not perform heterogeneity tests as only one study
      was identified. MAIN RESULTS: The repeat searches conducted in May 2012 did not
      identify any additional studies for inclusion. One study enrolling 130 infants of
      26 to 34 weeks PMA (mean postnatal age at entry 11 days) was identified and no
      identified study was excluded. The study was a double blind randomized controlled
      trial of high quality. Lactase treated feeds were initiated when enteral feedings
      provided > 75% of daily intake. None of the primary outcomes outlined in the
      protocol for this review and only one of the secondary outcomes, necrotizing
      enterocolitis (NEC) were reported on. The RR for NEC was 0.32 (95% CI 0.01 to
      7.79); the RD was -0.02 (95% CI -0.06 to 0.03) (a reduction which was not
      statistically significant). There was a statistically significant increase in
      weight gain at study day 10 in the lactase treated feeds group but not at any
      other time points. Overall, there was not a statistically significant effect on
      weight gain. No adverse effects were noted. AUTHORS' CONCLUSIONS: The only
      randomized trial to date provides no evidence of significant benefit to preterm
      infants from adding lactase to their feeds. Further research regarding
      effectiveness and safety are required before practice recommendations can be
      made. Randomized controlled trials comparing lactase versus placebo treated feeds
      and enrolling infants when enteral feeds are introduced are required. The primary
      and secondary outcomes for effectiveness and safety should include those
      identified in this review.

PMID- 23543536
TI  - Antibiotics for acute laryngitis in adults.
AB  - BACKGROUND: This is an updated version of the original review published in Issue
      2, 2007 of The Cochrane Library. Acute laryngitis is a common illness worldwide.
      Diagnosis is often made by case history alone and treatment is often directed
      toward controlling symptoms. OBJECTIVES: To assess the effectiveness and safety
      of different antibiotic therapies in adults with acute laryngitis. A secondary
      objective was to report the rates of adverse events associated with these
      treatments. SEARCH METHODS: We searched CENTRAL 2012, Issue 12, MEDLINE (January
      1966 to January week 3, 2013), EMBASE (1974 to January 2013), LILACS (1982 to
      January 2013) and BIOSIS (1980 to January 2013). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) comparing any antibiotic therapy with placebo for acute
      laryngitis. The main outcome was objective voice scores. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted and descriptively
      synthesised data. MAIN RESULTS: Only two trials met the study inclusion criteria
      after extensive literature searches. One hundred participants were randomised to
      receive either penicillin V (800 mg twice a day for five days), or an identical
      placebo, in a study of acute laryngitis in adults. A tape recording of each
      patient reading a standardised text was obtained during the first visit,
      subsequently during re-examination after one and two weeks, and at follow-up
      after two to six months. No significant differences were found between the
      groups. The trial also measured symptoms reported by participants and found no
      significant differences.The second trial investigated erythromycin for treating
      acute laryngitis in 106 adults. The mean objective voice scores measured at the
      first visit, at re-examination after one and two weeks, and at follow-up after
      two to six months did not significantly differ between control and intervention
      groups. At one week there were significant beneficial differences in the severity
      of reported vocal symptoms as judged by the participants (P = 0.042). Comparing
      the erythromycin and placebo groups on subjective voice scores, the a priori risk
      ratio (RR) was 0.7 (95% confidence interval (CI) 0.51 to 0.96, P = 0.034) and the
      number needed to treat for an additional beneficial outcome (NNTB) was 4.5.
      AUTHORS' CONCLUSIONS: Antibiotics appear to have no benefit in treating acute
      laryngitis. Erythromycin could reduce voice disturbance at one week and cough at
      two weeks when measured subjectively. We consider that these outcomes are not
      relevant in clinical practice. The implications for practice are that prescribing
      antibiotics should not be done in the first instance as they will not objectively
      improve symptoms.

PMID- 23543537
TI  - Consumer-providers of care for adult clients of statutory mental health services.
AB  - BACKGROUND: In mental health services, the past several decades has seen a slow
      but steady trend towards employment of past or present consumers of the service
      to work alongside mental health professionals in providing services. However the
      effects of this employment on clients (service recipients) and services has
      remained unclear.We conducted a systematic review of randomised trials assessing
      the effects of employing consumers of mental health services as providers of
      statutory mental health services to clients. In this review this role is called
      'consumer-provider' and the term 'statutory mental health services' refers to
      public services, those required by statute or law, or public services involving
      statutory duties. The consumer-provider's role can encompass peer support,
      coaching, advocacy, case management or outreach, crisis worker or assertive
      community treatment worker, or providing social support programmes. OBJECTIVES:
      To assess the effects of employing current or past adult consumers of mental
      health services as providers of statutory mental health services. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library 2012, Issue 3), MEDLINE (OvidSP) (1950 to March 2012), EMBASE
      (OvidSP) (1988 to March 2012), PsycINFO (OvidSP) (1806 to March 2012), CINAHL
      (EBSCOhost) (1981 to March 2009), Current Contents (OvidSP) (1993 to March 2012),
      and reference lists of relevant articles. SELECTION CRITERIA: Randomised
      controlled trials of current or past consumers of mental health services employed
      as providers ('consumer-providers') in statutory mental health services,
      comparing either: 1) consumers versus professionals employed to do the same role
      within a mental health service, or 2) mental health services with and without
      consumer-providers as an adjunct to the service. DATA COLLECTION AND ANALYSIS:
      Two review authors independently selected studies and extracted data. We
      contacted trialists for additional information. We conducted analyses using a
      random-effects model, pooling studies that measured the same outcome to provide a
      summary estimate of the effect across studies. We describe findings for each
      outcome in the text of the review with considerations of the potential impact of
      bias and the clinical importance of results, with input from a clinical expert.
      MAIN RESULTS: We included 11 randomised controlled trials involving 2796 people.
      The quality of these studies was moderate to low, with most of the studies at
      unclear risk of bias in terms of random sequence generation and allocation
      concealment, and high risk of bias for blinded outcome assessment and selective
      outcome reporting.Five trials involving 581 people compared consumer-providers to
      professionals in similar roles within mental health services (case management
      roles (4 trials), facilitating group therapy (1 trial)). There were no
      significant differences in client quality of life (mean difference (MD) -0.30,
      95% confidence interval (CI) -0.80 to 0.20); depression (data not pooled),
      general mental health symptoms (standardised mean difference (SMD) -0.24, 95% CI 
      0.52 to 0.05); client satisfaction with treatment (SMD -0.22, 95% CI -0.69 to
      0.25), client or professional ratings of client-manager relationship; use of
      mental health services, hospital admissions and length of stay; or attrition
      (risk ratio 0.80, 95% CI 0.58 to 1.09) between mental health teams involving
      consumer-providers or professional staff in similar roles.There was a small
      reduction in crisis and emergency service use for clients receiving care
      involving consumer-providers (SMD -0.34 (95%CI -0.60 to -0.07). Past or present
      consumers who provided mental health services did so differently than
      professionals; they spent more time face-to-face with clients, and less time in
      the office, on the telephone, with clients' friends and family, or at provider
      agencies.Six trials involving 2215 people compared mental health services with or
      without the addition of consumer-providers. There were no significant differences
      in psychosocial outcomes (quality of life, empowerment, function, social
      relations), client satisfaction with service provision (SMD 0.76, 95% CI -0.59 to
      2.10) and with staff (SMD 0.18, 95% CI -0.43 to 0.79), attendance rates (SMD 0.52
      (95% CI -0.07 to 1.11), hospital admissions and length of stay, or attrition
      (risk ratio 1.29, 95% CI 0.72 to 2.31) between groups with consumer-providers as
      an adjunct to professional-led care and those receiving usual care from health
      professionals alone. One study found a small difference favouring the
      intervention group for both client and staff ratings of clients' needs having
      been met, although detection bias may have affected the latter. None of the six
      studies in this comparison reported client mental health outcomes.No studies in
      either comparison group reported data on adverse outcomes for clients, or the
      financial costs of service provision. AUTHORS' CONCLUSIONS: Involving consumer
      providers in mental health teams results in psychosocial, mental health symptom
      and service use outcomes for clients that were no better or worse than those
      achieved by professionals employed in similar roles, particularly for case
      management services.There is low quality evidence that involving consumer
      providers in mental health teams results in a small reduction in clients' use of
      crisis or emergency services. The nature of the consumer-providers' involvement
      differs compared to professionals, as do the resources required to support their
      involvement. The overall quality of the evidence is moderate to low. There is no
      evidence of harm associated with involving consumer-providers in mental health
      teams.Future randomised controlled trials of consumer-providers in mental health
      services should minimise bias through the use of adequate randomisation and
      concealment of allocation, blinding of outcome assessment where possible, the
      comprehensive reporting of outcome data, and the avoidance of contamination
      between treatment groups. Researchers should adhere to SPIRIT and CONSORT
      reporting standards for clinical trials.Future trials should further evaluate
      standardised measures of clients' mental health, adverse outcomes for clients,
      the potential benefits and harms to the consumer-providers themselves (including
      need to return to treatment), and the financial costs of the intervention. They
      should utilise consistent, validated measurement tools and include a clear
      description of the consumer-provider role (eg specific tasks, responsibilities
      and expected deliverables of the role) and relevant training for the role so that
      it can be readily implemented. The weight of evidence being strongly based in the
      United States, future research should be located in diverse settings including in
      low- and middle-income countries.

PMID- 23543538
TI  - Wound cleansing for pressure ulcers.
AB  - BACKGROUND: Pressure ulcers (also called pressure sores, bed sores and decubitus
      ulcers) are areas of tissue damage that occur in the elderly, malnourished or
      acutely ill, who cannot reposition themselves. Pressure ulcers impose a
      significant financial burden on health care systems and negatively affect quality
      of life. Wound cleansing is considered an important component of pressure ulcer
      care. OBJECTIVES: This systematic review seeks to answer the following question:
      what is the effect of wound cleansing solutions and wound cleansing techniques on
      the rate of healing of pressure ulcers? SEARCH METHODS: For this third update, we
      searched the Cochrane Wounds Group Specialised Register (searched 3 January
      2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2012, Issue 12); Ovid MEDLINE (2010 to November Week 3 2012); Ovid
      MEDLINE (In-Process & Other Non-Indexed Citations December 31, 2012); Ovid EMBASE
      (2010 to 2012 Week 52); and EBSCO CINAHL (2010 to 21 December 2012). SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing wound cleansing with no
      wound cleansing, or different wound cleansing solutions, or different cleansing
      techniques, were eligible for inclusion if they reported an objective measure of
      pressure ulcer healing. DATA COLLECTION AND ANALYSIS: Two review authors
      extracted data independently and resolved disagreements through discussion. A
      structured narrative summary of the included studies was conducted. For
      dichotomous outcomes, risk ratio (RR), plus 95% confidence intervals (CI) were
      calculated; for continuous outcomes, mean difference (MD), plus 95% CI were
      calculated. Meta analysis was not conducted because of the small number of
      diverse RCTs identified. Two review authors independently assessed each included
      study using the Cochrane Collaboration tool for assessing risk of bias. MAIN
      RESULTS: One additional eligible study was identified from the updated searches,
      one study was added to the table of excluded studies. A total of three studies
      (169 participants) met the inclusion criteria for the review. No studies compared
      cleansing with no cleansing. Two studies compared different wound cleansing
      solutions. A statistically significant improvement in Pressure Sore Status Tool
      scores occurred for wounds cleansed with saline spray containing Aloe vera,
      silver chloride and decyl glucoside (Vulnopur) compared with isotonic saline (P
      value = 0.025), but no statistically significant change in healing was seen when
      water was compared with saline (RR 3.00, 95% CI 0.21 to 41.89). One study
      compared cleansing techniques; for pressure ulcers cleansed with pulsatile
      lavage, compared with sham (the lavage flow was directed into a wash basin
      positioned adjacent to the wound and not visible to the participants), there was
      a statistically significant reduction in ulcer volume at the end of the three
      week study period in the lavage group compared with the sham group (MD -6.60, 95%
      CI-11.23, -1.97). AUTHORS' CONCLUSIONS: We identified three small studies
      addressing cleansing of pressure ulcers. One reported a statistically significant
      improvement in pressure ulcer healing for wounds cleansed with saline spray
      containing Aloe vera, silver chloride and decyl glucoside (Vulnopur) compared
      with isotonic saline solution, a further study reported no statistically
      significant change in healing was seen when wounds were cleaned with water was
      compared with saline. A final study compared pulsatile lavage with sham and found
      a significantly greater reduction in ulcer volume at the end of the study period
      in the lavage group compared with the sham group. The authors conclude that there
      is no good trial evidence to support use of any particular wound cleansing
      solution or technique for pressure ulcers.

PMID- 23543539
TI  - Topical treatments for chronic plaque psoriasis.
AB  - BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis, and it
      is characterised by redness, thickness, and scaling. First-line management of
      chronic plaque psoriasis is with topical treatments, including vitamin D
      analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic
      acid, and topical retinoids. OBJECTIVES: To compare the effectiveness,
      tolerability, and safety of topical treatments for chronic plaque psoriasis,
      relative to placebo, and to similarly compare vitamin D analogues (used alone or
      in combination) with other topical treatments. SEARCH METHODS: We updated our
      searches of the following databases to February 2011: the Cochrane Skin Group
      Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE
      (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference
      Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993),
      Dissertation Abstracts via DialogClassic (all publication years), and Inside
      Conferences (all publication years).We identified ongoing and unpublished studies
      from the UK Clinical Research Network Study Portfolio and the metaRegister of
      Controlled Trials. We checked the bibliographies of published studies and reviews
      for further references to relevant trials, and we contacted trialists and
      companies for information about newly published studies.A separate search for
      adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from
      2005).Final update searches for both RCTs and adverse effects were undertaken in
      August 2012. Although it has not been possible to incorporate RCTs and adverse
      effects studies identified through these final searches within this review, we
      will incorporate these into the next update. SELECTION CRITERIA: Randomised
      trials comparing active topical treatments against placebo or against vitamin D
      analogues (used alone or in combination) in people with chronic plaque psoriasis.
      DATA COLLECTION AND ANALYSIS: One author extracted study data and assessed study
      quality. A second author checked these data. We routinely contacted trialists and
      companies for missing data. We also extracted data on withdrawals and on local
      and systemic adverse events. We defined long-term trials as those with a duration
      of at least 24 weeks. MAIN RESULTS: This update added 48 trials and provided
      evidence on 7 new active treatments. In total, the review included 177 randomised
      controlled trials, with 34,808 participants, including 26 trials of scalp
      psoriasis and 6 trials of inverse psoriasis, facial psoriasis, or both. The
      number of included studies counted by Review Manager (RevMan) is higher than
      these figures (190) because we entered each study reporting a placebo and an
      active comparison into the 'Characteristics of included studies' table as 2
      studies.When used on the body, most vitamin D analogues were significantly more
      effective than placebo, with the standardised mean difference (SMD) ranging from 
      0.67 (95% CI -1.04 to -0.30; 1 study, 119 participants) for twice-daily
      becocalcidiol to SMD -1.66 (95% CI -2.66 to -0.67; 1 study, 11 participants) for
      once-daily paricalcitol. On a 6-point global improvement scale, these effects
      translate into 0.8 and 1.9 points, respectively. Most corticosteroids also
      performed better than placebo; potent corticosteroids (SMD -0.89; 95% CI -1.06 to
      -0.72; I2 statistic = 65.1%; 14 studies, 2011 participants) had smaller benefits
      than very potent corticosteroids (SMD -1.56; 95% CI -1.87 to -1.26); I2 statistic
      = 81.7%; 10 studies, 1264 participants). On a 6-point improvement scale, these
      benefits equate to 1.0 and 1.8 points, respectively. Dithranol, combined
      treatment with vitamin D/corticosteroid, and tazarotene all performed
      significantly better than placebo.Head-to-head comparisons of vitamin D for
      psoriasis of the body against potent or very potent corticosteroids had mixed
      findings. For both body and scalp psoriasis, combined treatment with vitamin D
      and corticosteroid performed significantly better than vitamin D alone or
      corticosteroid alone. Vitamin D generally performed better than coal tar, but
      findings relative to dithranol were mixed. When applied to psoriasis of the
      scalp, vitamin D was significantly less effective than both potent
      corticosteroids and very potent corticosteroids. Indirect evidence from placebo
      controlled trials supported these findings.For both body and scalp psoriasis,
      potent corticosteroids were less likely than vitamin D to cause local adverse
      events, such as burning or irritation. Combined treatment with vitamin
      D/corticosteroid on either the body or the scalp was tolerated as well as potent
      corticosteroids, and significantly better than vitamin D alone. Only 25 trials
      assessed clinical cutaneous dermal atrophy; few cases were detected, but trials
      reported insufficient information to determine whether assessment methods were
      robust. Clinical measurements of dermal atrophy are insensitive and detect only
      the most severe cases. No comparison of topical agents found a significant
      difference in systemic adverse effects. AUTHORS' CONCLUSIONS: Corticosteroids
      perform at least as well as vitamin D analogues, and they are associated with a
      lower incidence of local adverse events. However, for people with chronic plaque
      psoriasis receiving long-term treatment with corticosteroids, there remains a
      lack of evidence about the risk of skin dermal atrophy. Further research is
      required to inform long-term maintenance treatment and provide appropriate safety
      data.

PMID- 23543540
TI  - Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV
      infection and AIDS.
AB  - BACKGROUND: UNAIDS estimates that 34 million people are currently living with the
      human immunodeficiency virus (HIV) worldwide. Currently recommended regimens for
      initiating HIV treatment consist of either a non-nucleoside reverse transcriptase
      inhibitor (NNRTI) or ritonavir-boosted protease inhibitor (PI) combined with two
      nucleoside reverse transcriptase inhibitors (NRTIs). However, there may be some
      patients for whom NNRTIs and PIs may not be appropriate. This is an update of the
      review published in the Cochrane Library Issue 3, 2009. OBJECTIVES: To evaluate
      the effects of any fixed-dose combination of three NRTIs (co-formulated abacavir
      lamivudine-zidovudine) for initial treatment of HIV infection. SEARCH METHODS:
      Between December 2010 and July 2011, we used standard Cochrane methods to search
      electronic databases and conference proceedings with relevant search terms
      without limits to language or publication status. SELECTION CRITERIA: We selected
      randomised controlled trials (RCTs) with a minimum follow-up time of six months
      which compared co-formulated abacavir-lamivudine-zidovudine with either PI-based
      or NNRTI-based therapy among antiretroviral-naive HIV-infected patients aged at
      least 13 years. DATA COLLECTION AND ANALYSIS: Three authors independently
      selected eligible studies, assessed risk of bias, and extracted data; resolving
      discrepancies by consensus. We calculated the risk ratio (RR) or mean difference
      (MD), as appropriate, with its 95% confidence interval (CI) and conducted meta
      analysis using the random-effects method because of significant statistical
      heterogeneity (P<0.1). MAIN RESULTS: We identified 15 potentially eligible RCTs,
      four of which met our inclusion criteria. The four included RCTs were conducted
      in the United States of America (USA); USA, Puerto Rico, Guatemala, Dominican
      Republic, and Panama; USA and Mexico; and Botswana, respectively. The RCTs
      compared co-formulated abacavir-lamivudine-zidovudine to treatment based on
      efavirenz (NNRTI), nelfinavir (PI), atazanavir (PI), and co-formulated lopinavir
      ritonavir (PI), respectively. Overall, there was no significant difference in
      virological suppression between co-formulated abacavir-lamivudine-zidovudine and
      NNRTI- or PI-based therapy (4 trials; 2247 participants: RR 0.73, 95% CI 0.39 to
      1.36). However, the results showed significant heterogeneity (I(2)=79%); with co
      formulated abacavir-lamivudine-zidovudine inferior to NNRTI (1 trial, 1147
      participants: RR 0.35, 95%CI 0.26 to 0.49) but with a trend towards co-formulated
      abacavir-lamivudine-zidovudine being superior to PI (3 trials, 1110 participants:
      RR 1.07, 95%CI 1.00 to 1.16; I(2)=0%). We found no significant differences
      between co-formulated abacavir-lamivudine-zidovudine and either PI or NNRTI on
      CD4+ cell counts (3 trials, 1687 participants: MD -0.01, 95%CI -0.11 to 0.09;
      I(2)=0%), severe adverse events (4 trials: RR 1.22, 95%CI 0.78 to 1.92; I(2)=62%)
      and hypersensitivity reactions (4 trials: RR 4.04, 95% CI 0.41 to 40.02;
      I(2)=72%). Only two studies involving PIs reported data on the lipid profile. One
      study found that the mean increase in total cholesterol from baseline to 96 weeks
      was significantly lower with co-formulated abacavir-lamivudine-zidovudine than
      with nelfinavir, but there were no differences with triglyceride levels. The
      second study found the fasting lipid profile to be comparable in both co
      formulated abacavir-lamivudine-zidovudine and atazanavir arms at 48 weeks.The
      significant heterogeneity of effects for most outcomes evaluated was largely due
      to differences in the control therapy used in the included trials (i.e. NNRTIs or
      PIs). Using the GRADE approach, we rated the overall quality of the evidence on
      the relative effects of co-formulated abacavir-lamivudine-zidovudine for initial
      treatment of HIV infection as moderate. The main reason for downgrading the
      quality of the evidence was imprecision of the findings. The estimate of the
      treatment effect for each outcome has wide confidence intervals, which extend
      from the fixed-dose NRTI combination regimen being appreciably better to the
      regimen being appreciably worse than PI- or NNRTI-based regimens. AUTHORS'
      CONCLUSIONS: This review provides evidence that co-formulated abacavir-lamivudine
      zidovudine remains a viable option for initiating antiretroviral therapy,
      especially in HIV-infected patients with pre-existing hyperlipidaemia. The varied
      geographical locations of the included trials augment the external validity of
      these findings. We are moderately confident in our estimate of the treatment
      effects of the triple NRTI regimen as initial therapy for HIV infection. In the
      context of the GRADE approach, such moderate quality of evidence implies that the
      true effects of the regimen are likely to be close to the estimate of effects
      found in this review; but there is a possibility that they could be substantially
      different.  Further research should be geared towards defining the subgroup of
      HIV patients for whom this regimen will be most beneficial.

PMID- 23543541
TI  - Corticosteroids for preventing postherpetic neuralgia.
AB  - BACKGROUND: Postherpetic neuralgia is a common, serious painful complication of
      herpes zoster. Corticosteroids are anti-inflammatory and might be beneficial.
      This is an update of a review first published in 2008 and previously updated in
      2010. OBJECTIVES: To examine the efficacy of corticosteroids in preventing
      postherpetic neuralgia. SEARCH METHODS: We updated the searches for randomised
      controlled trials (RCTs) of corticosteroids for preventing postherpetic neuralgia
      in the Cochrane Neuromuscular Disease Group Specialized Register (16 April 2012),
      CENTRAL (2012, Issue 3), MEDLINE (January 1966 to April 2012), EMBASE (January
      1980 to April 2012), LILACS (January 1982 to April 2012), and the Chinese
      Biomedical Retrieval System (1978 to 2012). We also reviewed the bibliographies
      of identified trials, contacted authors and approached pharmaceutical companies
      to identify additional published or unpublished data. SELECTION CRITERIA: We
      included all RCTs involving corticosteroids given by oral, intramuscular, or
      intravenous routes for people of all ages with herpes zoster of all degrees of
      severity within seven days after onset, compared with no treatment or placebo but
      not with other treatments. We did not include quasi-RCTs (trials in which a
      systematic method of randomisation such as alternation or hospital number was
      used). DATA COLLECTION AND ANALYSIS: Two authors identified potential articles,
      extracted data, and independently assessed the risk of bias of each trial.
      Disagreement was resolved by discussion among the co-authors. MAIN RESULTS: Five
      trials were included with 787 participants in total. All were randomised, double
      blind, placebo-controlled parallel-group studies. We conducted a meta-analysis of
      two trials (114 participants) and the results gave moderate quality evidence that
      oral corticosteroids did not prevent postherpetic neuralgia six months after the
      onset of herpes (RR 0.95, 95% CI 0.45 to 1.99). One of these trials was at high
      risk of bias because of incomplete outcome data, the other was at low risk of
      bias overall. The three other trials that fulfilled our inclusion criteria were
      not included in the meta-analysis because the outcomes were reported at less than
      one month or not in sufficient detail to add to the meta-analysis. These three
      trials were generally at low risk of bias. Adverse events during or within two
      weeks after stopping treatment were reported in all five included trials. There
      were no significant differences in serious or non-serious adverse events between
      the corticosteroid and placebo groups. There was also no significant difference
      between the treatment groups and placebo groups in other secondary outcome
      analyses and subgroup analyses. The review was first published in 2008 and no new
      RCTs were identified for inclusion in subsequent updates in 2010 and 2012.
      AUTHORS' CONCLUSIONS: There is moderate quality evidence that corticosteroids
      given acutely during zoster infection are ineffective in preventing postherpetic
      neuralgia. In people with acute herpes zoster the risks of administration of
      corticosteroids do not appear to be greater than with placebo, based on moderate
      quality evidence. Corticosteroids have been recommended to relieve the zoster
      associated pain in the acute phase of disease. If further research is designed to
      evaluate the efficacy of corticosteroids for herpes zoster, long-term follow-up
      should be included to observe their effect on the transition from acute pain to
      postherpetic neuralgia. Future trials should include measurements of function and
      quality of life.

PMID- 23543542
TI  - Parenting interventions for the prevention of unintentional injuries in
      childhood.
AB  - BACKGROUND: Parent education and training programmes can improve maternal
      psychosocial health, child behavioural problems and parenting practices. This
      review assesses the effects of parenting interventions for reducing child injury.
      OBJECTIVES: To assess the effects of parenting interventions for preventing
      unintentional injury in children aged under 18 years and for increasing
      possession and use of safety equipment and safety practices by parents. SEARCH
      METHODS: We searched CENTRAL, MEDLINE, EMBASE, BIOSIS Preview, PsycINFO,
      Sociological Abstracts, Social Science Citation Index, CINAHL, ProQuest
      Dissertations and Theses, ERIC, DARE, ASSIA, Web of Science, SIGLE and ZETOC. We
      also handsearched abstracts from the World Conferences on Injury Prevention &
      Control and the journal Injury Prevention. The searches were conducted in January
      2011. SELECTION CRITERIA: We included randomised controlled trials (RCTs), non
      randomised controlled trials (non-RCTs) and controlled before and after studies
      (CBAs), which evaluated parenting interventions administered to parents of
      children aged 18 years and under, and reported outcome data on injuries for
      children (unintentional or unspecified intent), possession and use of safety
      equipment or safety practices (including the Home Observation for Measurement of
      the Environment (HOME) scale which contained an assessment of home safety) by
      parents. Parenting interventions were defined as those with a specified protocol,
      manual or curriculum aimed at changing knowledge, attitudes or skills covering a
      range of parenting topics. DATA COLLECTION AND ANALYSIS: Studies were selected,
      data were extracted and quality appraised independently by two authors. Pooled
      relative risks (RR) were estimated using random effect models. MAIN RESULTS:
      Twenty two studies were included in the review: 16 RCTs, two non-RCTs, one
      partially randomised trial which contained two randomised intervention arms and
      one non-randomised control arm, two CBA studies and one quasi randomised
      controlled trial. Seventeen studies provided interventions comprising parenting
      education and other support services; 15 of which were home visiting programmes
      and two of which were paediatric practice-based interventions. Two provided
      solely educational interventions. Nineteen studies recruited families who were
      from socio-economically disadvantaged populations, were at risk of adverse child
      outcomes or people who may benefit from extra support, such as single mothers,
      teenage mothers, first time mothers and mothers with learning difficulties. Ten
      RCTs involving 5074 participants were included in the meta-analysis, which
      indicated that intervention families had a statistically significant lower risk
      of injury than control families (RR 0.83, 95% CI 0.73 to 0.94). Sensitivity
      analyses undertaken including only RCTs at low risk of various sources of bias
      found the findings to be robust to including only those studies at low risk of
      detection bias in terms of blinded outcome assessment and attrition bias in terms
      of follow up of fewer than 80% of participants in each arm. When analyses were
      restricted to studies at low risk of selection bias in terms of inadequate
      allocation concealment the effect size was no longer statistically significant.
      Several studies found statistically significant fewer home hazards or a greater
      number of safety practices in intervention families. Of ten studies reporting
      scores on the HOME scale, data from three RCTs were included in a meta-analysis
      which found no evidence of a difference in quality of the home environment
      between treatment arms (mean difference 0.57, 95% CI -0.59 to 1.72). Most of the
      studies reporting home safety practices, home hazards or composite home safety
      scores found statistically significant effects favouring intervention arm
      families. Overall, using GRADE, the quality of the evidence was rated as
      moderate. AUTHORS' CONCLUSIONS: Parenting interventions, most commonly provided
      within the home using multi-faceted interventions are effective in reducing child
      injury. There is fairly consistent evidence that they also improve home safety.
      The evidence relates mainly to interventions provided to families from
      disadvantaged populations, who are at risk of adverse child health outcomes or
      whose families may benefit from extra support. Further research is required to
      explore mechanisms by which these interventions may reduce injury, the features
      of parenting interventions that are necessary or sufficient to reduce injury and
      the generalisability to different population groups.

PMID- 23543543
TI  - Educational games for health professionals.
AB  - BACKGROUND: The use of games as an educational strategy has the potential to
      improve health professionals' performance (e.g. adherence to standards of care)
      through improving their knowledge, skills and attitudes. OBJECTIVES: The
      objective was to assess the effect of educational games on health professionals'
      performance, knowledge, skills, attitude and satisfaction, and on patient
      outcomes. SEARCH METHODS: We searched the following databases in January 2012:
      MEDLINE, AMED, CINAHL, Cochrane Central Database of Controlled Trials, EMBASE,
      EPOC Register, ERIC, Proquest Dissertations & Theses Database, and PsycINFO.
      Related reviews were sought in DARE and the above named databases. Database
      searches identified 1546 citations. We also screened the reference lists of
      included studies in relevant reviews, contacted authors of relevant papers and
      reviews, and searched ISI Web of Science for papers citing studies included in
      the review. These search methods identified an additional 62 unique citations for
      a total of 1608 for this update. SELECTION CRITERIA: We included randomized
      controlled trials (RCT), controlled clinical trials (CCT), controlled before and
      after (CBA) and interrupted time-series analysis (ITS). Study participants were
      qualified health professionals or in postgraduate training. The intervention was
      an educational game with "a form of competitive activity or sport played
      according to rules". DATA COLLECTION AND ANALYSIS: Using a standardized data form
      we extracted data on methodological quality, participants, interventions and
      outcomes of interest that included patient outcomes, professional behavior
      (process of care outcomes), and professional's knowledge, skills, attitude and
      satisfaction. MAIN RESULTS: The search strategy identified a total of 2079 unique
      citations. Out of 84 potentially eligible citations, we included two RCTs. The
      game evaluated in the first study used as a reinforcement technique, was based on
      the television game show "Family Feud" and focused on infection control. The
      study did not assess any patient or process of care outcomes. The group that was
      randomized to the game had statistically higher scores on the knowledge test (P =
      0.02). The second study compared game-based learning ("Snakes and Ladders" board
      game) with traditional case-based learning of stroke prevention and management.
      The effect on knowledge was not statistically different between the two groups
      immediately and 3 months after the intervention. The level of reported enjoyment
      was higher in the game-based group. AUTHORS' CONCLUSIONS: The findings of this
      systematic review neither confirm nor refute the utility of games as a teaching
      strategy for health professionals. There is a need for additional high-quality
      research to explore the impact of educational games on patient and performance
      outcomes.

PMID- 23543544
TI  - Prebiotics in infants for prevention of allergy.
AB  - BACKGROUND: Prebiotics (commonly oligosaccharides) added to infant feeds have the
      potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES:
      To determine the effect of prebiotic given to infants for the prevention of
      allergy. SEARCH METHODS: We performed an updated search in August 2012 of the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2012, Issue 8), MEDLINE, EMBASE, conference proceedings, citations, expert
      informants and clinical trials registries. SELECTION CRITERIA: Randomised and
      quasi-randomised controlled trials that compared the use of a prebiotic to no
      prebiotic, or a specific prebiotic compared to a different prebiotic in infants
      for prevention of allergy. DATA COLLECTION AND ANALYSIS: Assessment of trial
      quality, data extraction and synthesis of data were performed using the standard
      methods of The Cochrane Collaboration. MAIN RESULTS: The 2012 update identified
      13 studies classified as ongoing or awaiting classification (yet to report
      allergy outcomes). Forty-three studies were excluded, primarily as no allergy
      data were reported, although none of these enrolled infants were at high risk of
      allergy. Four studies enrolling 1428 infants were eligible for inclusion. All
      studies were at high risk of attrition bias. Allergy outcomes were reported from
      four months to two years of age.Meta-analysis of two studies (226 infants) found
      no significant difference in infant asthma although significant heterogeneity was
      found between studies. Meta-analysis of four studies found a significant
      reduction in eczema (1218 infants, typical risk ratio 0.68, 95% CI 0.48 to 0.97;
      typical risk difference -0.04, 95% CI -0.07 to -0.00; number needed to treat to
      benefit (NNTB) 25, 95% CI 14 to > 100; P = 0.03). No statistically significant
      heterogeneity was found between studies. One study reported no significant
      difference in urticaria.No statistically significant subgroup differences were
      found according to infant risk of allergy or type of infant feed. However,
      individual studies reported a significant reduction in asthma and eczema from
      supplementation with a mixture of galacto- and fructo-oligosaccharide (GOS/FOS
      9:1 ratio) (8 g/L) in infants at high risk of allergy; and in eczema from
      supplementation with GOS/FOS (9:1) (6.8 g/L) and acidic oligosacccharide (1.2
      g/L) in infants not selected for allergy risk. AUTHORS' CONCLUSIONS: Further
      research is needed before routine use of prebiotics can be recommended for
      prevention of allergy in formula fed infants. There is some evidence that a
      prebiotic supplement added to infant feeds may prevent eczema. It is unclear
      whether the use of prebiotic should be restricted to infants at high risk of
      allergy or may have an effect in low risk populations; or whether it may have an
      effect on other allergic diseases including asthma.

PMID- 23543545
TI  - Interventions to improve professional adherence to guidelines for prevention of
      device-related infections.
AB  - BACKGROUND: Healthcare-associated infections (HAIs) are a major threat to patient
      safety, and are associated with mortality rates varying from 5% to 35%. Important
      risk factors associated with HAIs are the use of invasive medical devices (e.g.
      central lines, urinary catheters and mechanical ventilators), and poor staff
      adherence to infection prevention practices during insertion and care for the
      devices when in place. There are specific risk profiles for each device, but in
      general, the breakdown of aseptic technique during insertion and care for the
      device, as well as the duration of device use, are important factors for the
      development of these serious and costly infections. OBJECTIVES: To assess the
      effectiveness of different interventions, alone or in combination, which target
      healthcare professionals or healthcare organisations to improve professional
      adherence to infection control guidelines on device-related infection rates and
      measures of adherence. SEARCH METHODS: We searched the following electronic
      databases for primary studies up to June 2012: the Cochrane Effective Paractice
      and Organisation of Care (EPOC) Group Specialised Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. We searched
      reference lists and contacted authors of included studies. We also searched the
      Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of
      Effectiveness (DARE) for related reviews. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs),
      controlled before-after (CBA) studies and interrupted time series (ITS) studies
      that complied with the Cochrane EPOC Group methodological criteria, and that
      evaluated interventions to improve professional adherence to guidelines for the
      prevention of device-related infections. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data and assessed the risk of bias of each
      included study using the Cochrane EPOC 'Risk of bias' tool. We contacted authors
      of original papers to obtain missing information. MAIN RESULTS: We included 13
      studies: one cluster randomised controlled trial (CRCT) and 12 ITS studies,
      involving 40 hospitals, 51 intensive care units (ICUs), 27 wards, and more than
      3504 patients and 1406 healthcare professionals. Six of the included studies
      targeted adherence to guidelines to prevent central line-associated blood stream
      infections (CLABSIs); another six studies targeted adherence to guidelines to
      prevent ventilator-associated pneumonia (VAP), and one study focused on
      interventions to improve urinary catheter practices. We judged all included
      studies to be at moderate or high risk of bias.The largest median effect on rates
      of VAP was found at nine months follow-up with a decrease of 7.36 (-10.82 to
      3.14) cases per 1000 ventilator days (five studies and 15 sites). The one
      included cluster randomised controlled trial (CRCT) observed, improved urinary
      catheter practices five weeks after the intervention (absolute difference 12.2
      percentage points), however, the statistical significance of this is unknown
      given a unit of analysis error. It is worth noting that N = 6 interventions that
      did result in significantly decreased infection rates involved more than one
      active intervention, which in some cases, was repeatedly administered over time,
      and further, that one intervention involving specialised oral care personnel
      showed the largest step change (-22.9 cases per 1000 ventilator days (standard
      error (SE) 4.0), and also the largest slope change (-6.45 cases per 1000
      ventilator days (SE 1.42, P = 0.002)) among the included studies. We attempted to
      combine the results for studies targeting the same indwelling medical device
      (central line catheters or mechanical ventilators) and reporting the same
      outcomes (CLABSI and VAP rate) in two separate meta-analyses, but due to very
      high statistical heterogeneity among included studies (I(2) up to 97%), we did
      not retain these analyses. Six of the included studies reported post-intervention
      adherence scores ranging from 14% to 98%. The effect on rates of infection were
      mixed and the effect sizes were small, with the largest median effect for the
      change in level (interquartile range (IQR)) for the six CLABSI studies being
      observed at three months follow-up was a decrease of 0.6 (-2.74 to 0.28) cases
      per 1000 central line days (six studies and 36 sites). This change was not
      sustained over longer follow-up times. AUTHORS' CONCLUSIONS: The low to very low
      quality of the evidence of studies included in this review provides insufficient
      evidence to determine with certainty which interventions are most effective in
      changing professional behaviour and in what contexts. However, interventions that
      may be worth further study are educational interventions involving more than one
      active element and that are repeatedly administered over time, and interventions
      employing specialised personnel, who are focused on an aspect of care that is
      supported by evidence e.g. dentists/dental auxiliaries performing oral care for
      VAP prevention.

PMID- 23543546
TI  - Exit interviews to reduce turnover amongst healthcare professionals.
AB  - BACKGROUND: Exit interviews are widely used in healthcare organisations to
      identify reasons for staff attrition, yet their usefulness in limiting turnover
      is unclear. OBJECTIVES: To determine the effectiveness of various exit interview
      strategies in decreasing turnover rates amongst healthcare professionals. SEARCH
      METHODS: We searched the Cochrane EPOC Group Specialised Register; Cochrane
      Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid
      (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID
      (1806-) between October 31 and November 6, 2012. We also screened the reference
      lists of included studies and relevant reviews; and searched trial registries for
      planned and on-going trials. We did not restrict searches by language or
      publication date. SELECTION CRITERIA: Randomised controlled trials, controlled
      clinical trials, controlled before-after studies and interrupted time series
      studies comparing turnover rates between healthcare professionals who had
      undergone one form of exit interview with another form of exit interview or with
      no interview. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted data. MAIN RESULTS: The original search
      identified 1560 citations, of which we considered 19 potentially relevant. The
      two authors independently reviewed the abstracts of these studies and retrieved
      the full texts of eight studies. We excluded all eight following independent
      assessment; they were either interviews, commentaries on how to do an exit
      interview or descriptive studies about reasons for leaving. We found no trials
      that matched our inclusion criteria. For this first update, we screened 2220
      citations and identified no new trials. AUTHORS' CONCLUSIONS: Evidence about the
      effectiveness of exit interviews to reduce turnover is currently not available.
      However, exit interviews may provide useful information about the work
      environment which, in turn, may be useful in the development of interventions to
      reduce turnover.

PMID- 23543547
TI  - Folic acid supplementation during pregnancy for maternal health and pregnancy
      outcomes.
AB  - BACKGROUND: During pregnancy, fetal growth causes an increase in the total number
      of rapidly dividing cells, which leads to increased requirements for folate.
      Inadequate folate intake leads to a decrease in serum folate concentration,
      resulting in a decrease in erythrocyte folate concentration, a rise in
      homocysteine concentration, and megaloblastic changes in the bone marrow and
      other tissues with rapidly dividing cells OBJECTIVES: To assess the effectiveness
      of oral folic acid supplementation alone or with other micronutrients versus no
      folic acid (placebo or same micronutrients but no folic acid) during pregnancy on
      haematological and biochemical parameters during pregnancy and on pregnancy
      outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (31 December 2012) and we contacted major organisations
      working in micronutrient supplementation, including UNICEF Nutrition Section,
      World Health Organization (WHO) Maternal and Reproductive Health, WHO Nutrition
      Division, and National Center on Birth defects and Developmnetal Disabilities, US
      Centers for Disease Control and Prevention (CDC). SELECTION CRITERIA: All
      randomised, cluster-randomised and cross-over controlled trials evaluating
      supplementation of folic acid alone or with other micronutrients versus no folic
      acid (placebo or same micronutrients but no folic acid) in pregnancy. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion, assessed risk of bias and extracted data. Data were checked for
      accuracy. MAIN RESULTS: Thirty-one trials involving 17,771 women are included in
      this review. This review found that folic acid supplementation has no impact on
      pregnancy outcomes such as preterm birth (risk ratio (RR) 1.01, 95% confidence
      interval (CI) 0.73 to 1.38; three studies, 2959 participants), and
      stillbirths/neonatal deaths (RR 1.33, 95% CI 0.96 to 1.85; three studies, 3110
      participants). However, improvements were seen in the mean birthweight (mean
      difference (MD) 135.75, 95% CI 47.85 to 223.68). On the other hand, the review
      found no impact on improving pre-delivery anaemia (average RR 0.62, 95% CI 0.35
      to 1.10; eight studies, 4149 participants; random-effects), mean pre-delivery
      haemoglobin level (MD -0.03, 95% CI -0.25 to 0.19; 12 studies, 1806
      participants), mean pre-delivery serum folate levels (standardised mean
      difference (SMD) 2.03, 95% CI 0.80 to 3.27; eight studies, 1250 participants;
      random-effects), and mean pre-delivery red cell folate levels (SMD 1.59, 95% CI 
      0.07 to 3.26; four studies, 427 participants; random-effects). However, a
      significant reduction was seen in the incidence of megaloblastic anaemia (RR
      0.21, 95% CI 0.11 to 0.38, four studies, 3839 participants). AUTHORS'
      CONCLUSIONS: We found no conclusive evidence of benefit of folic acid
      supplementation during pregnancy on pregnancy outcomes.

PMID- 23543548
TI  - Regular treatment with salmeterol and inhaled steroids for chronic asthma:
      serious adverse events.
AB  - BACKGROUND: Epidemiological evidence has suggested a link between beta2-agonists
      and increased asthma mortality. There has been much debate about possible causal
      links for this association, and whether regular (daily) long-acting beta2
      agonists are safe. This is an updated systematic review. OBJECTIVES: To assess
      the risk of mortality and non-fatal serious adverse events in trials which
      randomised patients with chronic asthma to regular salmeterol and inhaled
      corticosteroids in comparison to the same dose of inhaled corticosteroids. SEARCH
      METHODS: We identified randomised trials using the Cochrane Airways Group
      Specialised Register of trials. We checked websites of clinical trial registers
      for unpublished trial data. Food and Drug Administration (FDA) submissions in
      relation to salmeterol were also checked. The date of the most recent search is
      August 2012. SELECTION CRITERIA: We included parallel design controlled clinical
      trials on patients of any age and severity of asthma if they randomised patients
      to treatment with regular salmeterol and inhaled corticosteroids (in separate or
      combined inhalers), and were of at least 12 weeks duration. DATA COLLECTION AND
      ANALYSIS: We conducted the review according to standard procedures expected by
      the Cochrane Collaboration. We obtained unpublished data on mortality and serious
      adverse events from the sponsors, and from FDA submissions. We assessed the
      quality of evidence according to GRADE recommendations. MAIN RESULTS: We have
      included 35 studies (13,447 participants) in adults and adolescents, and 5
      studies (1862 participants) in children in this review. We judged that the
      overall risk of bias was low, and we obtained data on serious adverse events from
      all studies. All except 542 adults (and none of the children) who were randomised
      to salmeterol were given fluticasone in the same (combination) inhaler.Seven
      deaths occurred in 6986 adults on regular salmeterol with inhaled corticosteroids
      (ICS), and seven deaths in 6461 adults on regular inhaled corticosteroids at the
      same dose. The difference was not statistically significant (Peto odds ratio (OR)
      0.90; 95% confidence interval (CI) 0.31 to 2.60, moderate quality evidence). The
      risk of dying from any cause in adults on ICS was 10 per 10,000, and on
      salmeterol and ICS we would expect between 3 and 26 deaths per 10,000. No deaths
      were reported in 1862 children, and no deaths were reported to be asthma-related
      in adults or children.Non-fatal serious adverse events of any cause were reported
      in 167 adults on regular salmeterol with ICS, compared to 135 adults on regular
      ICS; again this was not a statistically significant increase (Peto OR 1.15; 95%
      CI 0.91 to 1.44, moderate quality evidence). The frequency of serious adverse
      events was 21 per 1000 in the adults treated with ICS and 24 per 1000 in those
      treated with salmeterol and ICS. The absolute difference in the risk of non-fatal
      serious adverse events was an increase of 3 per 1000, that was not statistically
      significant (risk difference (RD) 0.003; 95% CI -0.002 to 0.008).There were 6 of
      930 children with serious adverse events on regular salmeterol with ICS, compared
      to 5 out of 932 on regular ICS: there was no significant difference between
      treatments (Peto OR 1.20; 95% CI 0.37 to 3.91, moderate quality evidence).Asthma
      related serious adverse events were reported in 29 and 23 adults in each group
      respectively, a non-significant difference (Peto OR 1.12; 95% CI 0.65 to 1.94,
      moderate quality evidence), and only 1 asthma-related event was reported in
      children in each treatment group. AUTHORS' CONCLUSIONS: We found no statistically
      significant differences in fatal or non-fatal serious adverse events in trials in
      which regular salmeterol was randomly allocated with ICS, in comparison to ICS
      alone at the same dose. Although 13,447 adults and 1862 children have now been
      included in trials, the frequency of adverse events is too low and the results
      are too imprecise to confidently rule out a relative increase in all cause
      mortality or non-fatal adverse events with salmeterol used in conjunction with
      ICS. However, the absolute difference between groups in the risk of serious
      adverse events was very small. We could not determine whether the increase in all
      cause non-fatal serious adverse events reported in the previous meta-analysis on
      regular salmeterol alone is abolished by the additional use of regular ICS. We
      await the results of large ongoing surveillance studies mandated by the FDA to
      provide more information. There were no asthma-related deaths and few asthma
      related serious adverse events. Clinical decisions and information for patients
      regarding regular use of salmeterol have to take into account the balance between
      known symptomatic benefits of salmeterol and the degree of uncertainty and
      concern associated with its potential harmful effects.

PMID- 23543549
TI  - Medical treatments for incomplete miscarriage.
AB  - BACKGROUND: Miscarriage occurs in 10% to 15% of pregnancies. The traditional
      treatment, after miscarriage, has been to perform surgery to remove any remaining
      placental tissues in the uterus ('evacuation of uterus'). However, medical
      treatments, or expectant care (no treatment), may also be effective, safe and
      acceptable. OBJECTIVES: To assess the effectiveness, safety and acceptability of
      any medical treatment for incomplete miscarriage (before 24 weeks). SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 November 2012) and reference lists of retrieved papers. SELECTION
      CRITERIA: Randomised controlled trials comparing medical treatment with expectant
      care or surgery or alternative methods of medical treatment. Quasi-randomised
      trials were excluded. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the studies for inclusion, assessed risk of bias and
      carried out data extraction. Data entry was checked. MAIN RESULTS: Twenty studies
      (4208 women) were included. There were no trials specifically of miscarriage
      treatment after 13 weeks' gestation.Three trials involving 335 women compared
      misoprostol treatment (all vaginally administered) with expectant care. There was
      no statistically significant difference in complete miscarriage (average risk
      ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; two studies, 150
      women, random-effects), or in the need for surgical evacuation (average RR 0.62,
      95% CI 0.17 to 2.26; two studies, 308 women, random-effects). There were few data
      on 'deaths or serious complications'.Twelve studies involving 2894 women
      addressed the comparison of misoprostol (six studies used oral administration,
      four studies used vaginal, one study sub-lingual, one study combined vaginal +
      oral) with surgical evacuation. There was a slightly lower incidence of complete
      miscarriage with misoprostol (average RR 0.97, 95% CI 0.95 to 0.99, 11 studies,
      2493 women, random-effects) but with success rate high for both methods. Overall,
      there were fewer surgical evacuations with misoprostol (average RR 0.06, 95% CI
      0.02 to 0.13; 11 studies, 2654 women, random-effects) but more unplanned
      procedures (average RR 5.82, 95% CI 2.93 to 11.56; nine studies, 2274 women,
      random-effects). There were few data on 'deaths or serious complications'. Nausea
      was more common with misoprostol (average RR 2.41, 95% CI 1.44 to 4.03; nine
      studies, 2179 women, random-effects).Five trials compared different routes of
      administration and/or doses of misoprostol. There was no clear evidence of one
      regimen being superior to another. Limited evidence suggests that women generally
      seem satisfied with their care. Long-term follow-up from one included study
      identified no difference in subsequent fertility between the three approaches.
      AUTHORS' CONCLUSIONS: The available evidence suggests that medical treatment,
      with misoprostol, and expectant care are both acceptable alternatives to routine
      surgical evacuation given the availability of health service resources to support
      all three approaches. Women experiencing miscarriage at less than 13 weeks should
      be offered an informed choice. Future studies should include long-term follow-up.

PMID- 23543550
TI  - Wound drainage after plastic and reconstructive surgery of the breast.
AB  - BACKGROUND: Wound drains are often used after plastic and reconstructive surgery
      of the breast, in order to reduce potential complications. It is unclear whether
      there is any evidence to support this practice and we therefore undertook a
      systematic review of the best evidence available. OBJECTIVES: To compare the
      safety and efficacy of the use of wound drains following elective plastic and
      reconstructive surgery procedures of the breast. SEARCH METHODS: We searched the
      Cochrane Wounds Group Specialised Register (searched 3 August 2012); The Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      7); Ovid MEDLINE (1950 to July Week 4 2012); Ovid MEDLINE (In-Process & Other Non
      Indexed Citations August 2, 2011); Ovid EMBASE (1980 to 2012 Week 30); and EBSCO
      CINAHL (1982 to 2 August 2012). There were no restrictions on the basis of date
      or language of publication. SELECTION CRITERIA: Two review authors undertook
      independent screening of the search results. All randomised trials that compared
      the use of a wound drain with no wound drain following plastic and reconstructive
      surgery of the breast (breast augmentation, breast reduction and breast
      reconstruction) in women were eligible. DATA COLLECTION AND ANALYSIS: Two review
      authors undertook independent data extraction of study characteristics,
      methodological quality and outcomes (e.g. infection, other wound complications,
      pain, and length of hospital stay). Risk of bias was assessed independently by
      two review authors. We calculated the risk ratio (RR) for dichotomous outcomes
      and mean differences (MD) for continuous outcomes, with 95% confidence intervals.
      Analysis was on an intention-to-treat basis. MAIN RESULTS: Three randomised
      trials were identified and included in the review out of 109 studies that were
      initially screened; all evaluated wound drainage after breast reduction surgery.
      In total there were 306 women in the three trials, and 505 breasts were studied
      (254 drained, and 251 who were not drained). Apart from a significantly shorter
      duration of hospital stay for those participants who did not have drains (MD
      0.77; 95% CI 0.40 to 1.14), there was no statistically significant impact of the
      use of drains on outcomes. AUTHORS' CONCLUSIONS: The limited evidence available
      shows no significant benefit of using post-operative wound drains in reduction
      mammoplasty, though hospital stay may be shorter when drains are not used. No
      data are available for breast augmentation or breast reconstruction, and this
      requires investigation.

PMID- 23543551
TI  - Damage control surgery for abdominal trauma.
AB  - BACKGROUND: Trauma is one of the leading causes of death in any age group. The
      'lethal triad' of acidosis, hypothermia, and coagulopathy has been recognized as
      a significant cause of death in patients with traumatic injuries. In order to
      prevent the lethal triad two factors are essential, early control of bleeding and
      prevention of further heat loss. In patients with major abdominal trauma, damage
      control surgery (DCS) avoids extensive procedures on unstable patients,
      stabilizes potentially fatal problems at initial operation, and applies staged
      surgery after successful initial resuscitation. It is not currently known whether
      DCS is superior to immediate surgery for patients with major abdominal trauma.
      OBJECTIVES: To assess the effects of damage control surgery compared to
      traditional immediate definitive surgical treatment for patients with major
      abdominal trauma. SEARCH METHODS: We searched the Cochrane Injuries Group
      Specialised Register, CENTRAL (The Cochrane Library 2012, Issue 12 of 12),
      MEDLINE, EMBASE, Web of Science: Science Citation Index & ISI Proceedings,
      Current Controlled Trials MetaRegister, Clinicaltrials.gov, Zetoc, and CINAHL for
      all published and unpublished randomised controlled trials. We did not restrict
      the searches by language, date, or publication status. The search was through
      December 2012. SELECTION CRITERIA: Randomised controlled trials of damage control
      surgery versus immediate traditional surgical repair were included in this
      review. We included patients with major abdominal trauma (Abbreviated Injury
      Scale > 3) who were undergoing surgery. Patient selection was crucial as patients
      with relatively simple abdominal injuries should not undergo unnecessary
      procedures. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the
      search results. MAIN RESULTS: A total of 2551 studies were identified by our
      search. No randomised controlled trials comparing DCS with immediate and
      definitive repair in patients with major abdominal trauma were found. A total of
      2551 studies were excluded because they were not relevant to the review topic and
      two studies were excluded with reasons after examining the full-text. AUTHORS'
      CONCLUSIONS: Evidence that supports the efficacy of damage control surgery with
      respect to traditional laparotomy in patients with major abdominal trauma is
      limited.

PMID- 23543552
TI  - Maternal position during caesarean section for preventing maternal and neonatal
      complications.
AB  - BACKGROUND: During caesarean section mothers can be in different positions.
      Theatre tables could be tilted laterally, upwards, downwards or flexed and wedges
      or cushions could be used. There is no consensus on the best positioning at
      present. OBJECTIVES: We assessed all available data on positioning of the mother
      to determine if there is an ideal position during caesarean section that would
      improve outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (20 August 2012), PubMed (1966 to 20 August
      2012) and manually searched the references of retrieved articles. SELECTION
      CRITERIA: Randomised trials of woman undergoing caesarean section comparing
      different positions. DATA COLLECTION AND ANALYSIS: Two review authors assessed
      eligibility, trial quality and extracted data. MAIN RESULTS: We identified 22
      studies with a total of 857 women included. We included 11 studies and excluded
      11. Included trials were of variably quality with small sample sizes. Most
      comparisons had data from single trials. This is a shortcoming and applicability
      of results is limited.The incidence of air embolism was not affected by head up
      versus horizontal position (average risk ratio (RR) 0.85; 95% confidence interval
      (CI) 0.28 to 2.57; Tau2 = 0.50; I2 = 74%).We found no change in hypotensive
      episodes when comparing left lateral tilt (RR 0.11; 95% CI 0.01 to 1.94), right
      lateral tilt (RR 1.25; 95% CI 0.39 to 3.99), a right lumbar pelvic wedge (RR
      0.85; CI 0.53 to1.37) and head down tilt (RR 1.07; 95% CI 0.81 to 1.42) with
      horizontal positions. We found no change in hypotensive episodes when comparing
      full lateral tilt with 15-degree tilt (RR 1.20; 95% CI 0.80 to 1.79). Hypotensive
      episodes were decreased with manual displacers (RR 0.11; 95% CI 0.03 to 0.45),
      and increased with a right lumbar wedge compared with a right pelvic wedge (RR
      1.64; 95% CI 1.07 to 2.53) and increased with a right lateral tilt compared with
      a left lateral tilt (RR 3.30; 95% CI 1.20 to 9.08).Position did not affect
      systolic blood pressure when comparing left lateral tilt (MD 2.70; 95% CI -1.47
      to 6.87) or head down tilt (MD -3.00; 95% CI -8.38 to 2.38) with horizontal
      positions, or full lateral tilt with 15-degree tilt (MD -5.00; 95% CI -11.45 to
      1.45). Manual displacers showed decreased fall in mean systolic blood pressure
      compared with left lateral tilt (MD -8.80; 95% CI -13.08 to -4.52).Position did
      not affect diastolic blood pressures when comparing left lateral tilt versus
      horizontal positions (MD-1.90; 95% CI -5.28 to 1.48). The mean diastolic pressure
      was lower in head down tilt (MD -7.00; 95% CI -12.05 to -1.95) when compared with
      horizontal positions.There were no statistically significant changes in maternal
      pulse rate, five-minute Apgars, maternal blood pH or cord blood pH when comparing
      different positions. AUTHORS' CONCLUSIONS: There is limited evidence to support
      or clearly disprove the value of the use of tilting or flexing the table, the use
      of wedges and cushions or the use of mechanical displacers. A left lateral tilt
      may be better than a right lateral tilt and manual displacers may be better than
      a left lateral tilt but larger studies with more robust data are needed to
      confirm these findings.

PMID- 23543553
TI  - Long-term effects of weight-reducing drugs in hypertensive patients.
AB  - BACKGROUND: All major guidelines for antihypertensive therapy recommend weight
      loss; anti-obesity drugs might be a helpful option. OBJECTIVES:  PRIMARY
      OBJECTIVES: To assess the long-term effects of pharmacologically induced
      reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause
      mortality - cardiovascular morbidity - adverse events SECONDARY OBJECTIVES: -
      changes in systolic and/or diastolic blood pressure - body weight reduction even
      though sibutramine and rimonabant have been withdrawn from the market. SEARCH
      METHODS: Studies were obtained from computerised searches of Ovid MEDLINE,
      EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews
      (status as of 17(th) August, 2012). SELECTION CRITERIA: Randomized controlled
      trials in adult hypertensive patients with a study duration of at least 24 weeks
      comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for
      weight loss with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed risk of bias and extracted data. Studies were pooled using fixed-effect
      meta-analysis in the absence of significant heterogeneity between studies
      (p>0.1). Otherwise, we used the random effects method and investigated the cause
      of heterogeneity. MAIN RESULTS: After the updated literature search, the number
      of studies remained the same, with eight studies comparing orlistat or
      sibutramine to placebo fulfilling our inclusion criteria. No relevant studies
      investigating rimonabant for weight loss were identified. No study included
      mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of
      gastrointestinal side effects was consistently higher in orlistat treated vs.
      placebo treated patients. Most frequent side effects with sibutramine were dry
      mouth, constipation and headache. Patients assigned to weight loss diets,
      orlistat or sibutramine reduced their body weight more effectively than patients
      in the usual care/placebo groups. Blood pressure reduction in patients treated
      with orlistat was for systolic blood pressure (SBP): weighted mean difference
      (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure
      (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP
      increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm
      Hg. AUTHORS' CONCLUSIONS: In patients with elevated blood pressure, orlistat and
      sibutramine reduced body weight to a similar degree. In the same trials, orlistat
      reduced blood pressure and sibutramine increased blood pressure. No trials
      investigating rimonabant in people with elevated blood pressure could be
      included. Long-term trials assessing the effect of orlistat, sibutramine and
      rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine
      have been withdrawn from the market for the time being.

PMID- 23543554
TI  - Acupuncture for acute management and rehabilitation of traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) can be life threatening depending on the
      severity of the insult to the brain. It can also cause a range of debilitating
      sequelae which require cognitive, motor, communication, emotional, or behavioral
      rehabilitation of varying intensity and duration. A number of studies conducted
      and published in China have suggested that acupuncture may be beneficial in the
      acute treatment and rehabilitation of TBI. OBJECTIVES: To determine the efficacy
      and safety of acupuncture in the acute management or rehabilitation (or both) of
      patients with a TBI, including cognitive, neurological, motor, communication,
      emotional, or behavioral complications, or a combination of such complications.
      SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register,
      Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE,
      EMBASE, CINAHL, AMED, PsycINFO and others. We also searched the Chinese
      Acupuncture Studies Register, the Studies Register of the Cochrane Complementary
      Medicine Field, NCCAM, and NIH Clinical Studies Database. Three major Mainland
      Chinese academic literature databases (CNKI, VIP and Wang Fang Data) were also
      searched using keywords in simplified Chinese. We searched all databases through
      December 2009, and some searches have been updated to October 2012. SELECTION
      CRITERIA: Randomized controlled studies evaluating different variants of
      acupuncture and involving participants of any age who had suffered a TBI.
      Included trials compared acupuncture with placebo or sham treatment, or
      acupuncture plus other treatments compared with the same other treatments. We
      excluded trials that only compared different variants of acupuncture or compared
      acupuncture alone against other treatments alone, as they did not yield the net
      effect of acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors
      identified potential articles from the literature search and extracted data
      independently using a data extraction form. We performed methodological
      assessment of included studies using the Cochrane Collaboration's tool for
      assessing risk of bias. We were unable to perform quantitative data analysis due
      to insufficient included studies and available data. MAIN RESULTS: Four RCTs,
      including 294 participants, reported outcomes specified by this review. Three
      investigated electro-acupuncture for TBI while one investigated acupuncture for
      acute TBI. The results seem to suggest that acupuncture is efficacious for these
      indications, however the low methodological quality of these studies renders the
      results questionable. No adverse effects of acupuncture were reported in any of
      the studies. AUTHORS' CONCLUSIONS: The low methodological quality of the included
      studies does not allow us to make conclusive judgments on the efficacy and safety
      of acupuncture in either the acute treatment and/or rehabilitation of TBI. Its
      beneficial role for these indications remains uncertain. Further research with
      high quality trials is required.

PMID- 23543555
TI  - Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and
      psychological symptoms in older people with dementia.
AB  - BACKGROUND: Antipsychotic agents are often used to treat neuropsychiatric
      symptoms (NPS) in dementia, although the literature is sceptical about their long
      term use for this indication. Their effectiveness is limited and there is concern
      about adverse effects, including higher mortality with long-term use. When
      behavioural strategies have failed and drug therapy is instituted, regular
      attempts to withdraw these drugs are recommended. Physicians, nurses and families
      of older people with dementia are often reluctant to try to stop antipsychotics,
      fearing deterioration of NPS. Strategies to reduce antipsychotic use have been
      proposed, but a systematic review of interventions aimed at withdrawal of
      antipsychotic agents in older people with dementia has not yet been performed.
      OBJECTIVES: To evaluate whether withdrawal of antipsychotic agents is successful
      in older people with dementia in community or nursing home settings, to list the
      different strategies for withdrawal of antipsychotic agents in older people with
      dementia and NPS, and to measure the effects of withdrawal of antipsychotic
      agents on behaviour. SEARCH METHODS: ALOIS, the Specialized Register of the
      Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library,
      MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, clinical trials registries and grey
      literature sources were searched on 23 November 2012. The search included the
      following terms: antipsychotic* or neuroleptic* or phenothiazines or
      butyrophenones or risperidone or olanzapine or haloperidol or prothipendyl or
      methotrimeprazine or clopenthixol or flupenthixol or clothiapine or metylperon or
      droperidol or pipamperone or benperidol or bromperidol or fluspirilene or
      pimozide or penfluridol or sulpiride or veralipride or levosulpiride or
      sultopride or aripiprazole or clozapine or quetiapine or thioridazine combined
      wither terms such as discontinu* or withdraw* or cessat* or reduce* or reducing
      or reduct* or taper* or stop*.ALOIS contains records from all major healthcare
      databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), as
      well as from many clinical trials registries and grey literature sources.
      SELECTION CRITERIA: Randomised, placebo-controlled trials comparing an
      antipsychotic withdrawal strategy to continuation of antipsychotics in people
      with dementia. DATA COLLECTION AND ANALYSIS: Review authors independently
      assessed trials for inclusion, rated their risk of bias and extracted data. MAIN
      RESULTS: We included nine trials with 606 randomised participants. Seven trials
      were conducted in nursing homes, one trial in an outpatient setting and one in
      both settings. In these trials, different types of antipsychotics prescribed at
      different doses were withdrawn. Both abrupt and gradual withdrawal schedules were
      used. The risk of bias of the included studies was generally low regarding
      blinding and outcome reporting and unclear for randomisation procedures and
      recruitment of participants.There was a wide variety of outcome measures. Our
      primary efficacy outcomes were success of withdrawal (i.e. remaining in study off
      antipsychotics) and NPS. Eight of nine trials reported no overall significant
      difference between groups on the primary outcomes, although in one pilot study of
      people with psychosis and agitation that had responded to haloperidol, time to
      relapse was significantly shorter in the discontinuation group (Chi(2) = 4.1, P
      value = 0.04). The ninth trial included people with psychosis or agitation who
      had responded well to risperidone therapy for four to eight months and reported
      that discontinuation led to an increased risk of relapse, that is, increase in
      the Neuropsychiatric Inventory (NPI)-core score of 30% or greater (P value =
      0.004, hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.09 to 3.45 at four
      months). The only outcome that could be pooled was the full NPI-score, used in
      two studies. For this outcome there was no significant difference between people
      withdrawn from and those continuing on antipsychotics at three months (mean
      difference (MD) -1.49, 95% CI -5.39 to 2.40). These two studies reported subgroup
      analyses according to baseline NPI-score (14 or less versus > 14). In one study,
      those with milder symptoms at baseline were significantly less agitated at three
      months in the discontinuation group (NPI-agitation, Mann-Whitney U test z = 2.4,
      P value = 0.018). In both studies, there was evidence of significant behavioural
      deterioration in people with more severe baseline NPS who were withdrawn from
      antipsychotics (Chi(2) = 6.8; P value = 0.009 for the marked symptom score in one
      study).Individual studies did not report significant differences between groups
      on any other outcome except one trial that found a significant difference in a
      measure of verbal fluency, favouring discontinuation. Most trials lacked power to
      detect clinically important differences between groups.Adverse events were not
      systematically assessed. In one trial there was a non-significant increase in
      mortality in people who continued antipsychotic treatment (5% to 8% greater than
      placebo, depending on the population analysed, measured at 12 months). This trend
      became significant three years after randomisation, but due to dropout and
      uncertainty about the use of antipsychotics in this follow-up period this result
      should be interpreted with caution. AUTHORS' CONCLUSIONS: Our findings suggest
      that many older people with Alzheimer's dementia and NPS can be withdrawn from
      chronic antipsychotic medication without detrimental effects on their behaviour.
      It remains uncertain whether withdrawal is beneficial for cognition or
      psychomotor status, but the results of this review suggest that discontinuation
      programmes could be incorporated into routine practice. However, two studies of
      people whose agitation or psychosis had previously responded well to
      antipsychotic treatment found an increased risk of relapse or shorter time to
      relapse after discontinuation. Two other studies suggest that people with more
      severe NPS at baseline could benefit from continuing their antipsychotic
      medication. In these people, withdrawal might not be recommended.

PMID- 23543556
TI  - Multidimensional rehabilitation programmes for adult cancer survivors.
AB  - BACKGROUND: Multidimensional rehabilitation programmes (MDRPs) have developed in
      response to the growing number of people living with and surviving cancer. MDRPs
      comprise a physical component and a psychosocial component. Studies of the
      effectiveness of these programmes have not been reviewed and synthesised.
      OBJECTIVES: To conduct a systematic review of studies examining the effectiveness
      of MDRPs in terms of maintaining or improving the physical and psychosocial well
      being of adult cancer survivors. SEARCH METHODS: We conducted electronic searches
      in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      CINAHL and PsychINFO up to February 2012. SELECTION CRITERIA: Selection criteria
      focused on randomised controlled trials (RCTs) of multidimensional interventions
      for adult cancer survivors. Interventions had to include a physical component and
      a psychosocial component and to have been carried out on two or more occasions
      following completion of primary cancer treatment. Outcomes had to be assessed
      using validated measures of physical health and psychosocial well-being. Non
      English language papers were included. DATA COLLECTION AND ANALYSIS: Pairs of
      review authors independently selected trials, rated their methodological quality
      and extracted relevant data. Although meta-analyses of primary and secondary
      endpoints were planned there was a high level of study heterogeneity and only one
      common outcome measure (SF-36) could be statistically synthesised. In addition,
      we conducted a narrative analysis of interventions, particularly in terms of
      inspecting and identifying intervention components, grouping or categorising
      interventions and examining potential common links and outcomes. MAIN RESULTS:
      Twelve RCTs (comprising 1669 participants) met the eligibility criteria. We
      judged five studies to have a moderate risk of bias and assessed the remaining
      seven as having a high risk of bias. It was possible to include SF-36 physical
      health component scores from five studies in a meta-analysis. Participating in a
      MDRP was associated with an increase in SF-36 physical health component scores
      (mean difference (MD) 2.22, 95% confidence interval (CI) 0.12 to 4.31, P = 0.04).
      The findings from the narrative analysis suggested that MDRPs with a single
      domain or outcome focus appeared to be more successful than programmes with
      multiple aims. In addition, programmes that comprised participants with different
      types of cancer compared to cancer site-specific programmes were more likely to
      show positive improvements in physical outcomes. The most effective mode of
      service delivery appeared to be face-to-face contact supplemented with at least
      one follow-up telephone call. There was no evidence to indicate that MDRPs which
      lasted longer than six months improved outcomes beyond the level attained at six
      months. In addition, there was no evidence to suggest that services were more
      effective if they were delivered by a particular type of health professional.
      AUTHORS' CONCLUSIONS: There is some evidence to support the effectiveness of
      brief, focused MDRPs for cancer survivors. Rigorous and methodologically sound
      clinical trials that include an economic analysis are required.

PMID- 23543557
TI  - De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or
      septic shock.
AB  - BACKGROUND: Mortality rates among patients with sepsis, severe sepsis or septic
      shock are highly variable throughout different regions or services and can be
      upwards of 50%. Empirical broad-spectrum antimicrobial treatment is aimed at
      achieving adequate antimicrobial therapy, thus reducing mortality; however, there
      is a risk that empirical broad-spectrum antimicrobial treatment can expose
      patients to overuse of antimicrobials. De-escalation has been proposed as a
      strategy to replace empirical broad-spectrum antimicrobial treatment by using a
      narrower antimicrobial therapy. This is done by reviewing the patient's microbial
      culture results and then making changes to the pharmacological agent or
      discontinuing a pharmacological combination. OBJECTIVES: To evaluate the
      effectiveness and safety of de-escalation antimicrobial treatment for adult
      patients diagnosed with sepsis, severe sepsis or septic shock caused by any micro
      organism. SEARCH METHODS: In this updated version, we searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      10); MEDLINE via PubMed (from inception to October 2012); EMBASE (from inception
      to October 2012); LILACS (from inception to October 2012); Current Controlled
      Trials; bibliographic references of relevant studies; and specialists in the
      area. We applied no language restriction. We had previously searched the
      databases to August 2010. SELECTION CRITERIA: We planned to include randomized
      controlled trials (RCTs) comparing de-escalation (based on culture results)
      versus standard therapy for adults with sepsis, severe sepsis or septic shock.
      The primary outcome was mortality (at 28 days, hospital discharge or at the end
      of the follow-up period). Studies including patients initially treated with an
      empirical but not adequate antimicrobial therapy were not considered for
      inclusion. DATA COLLECTION AND ANALYSIS: Two authors planned to independently
      select and extract data and to evaluate methodological quality of all studies. We
      planned to use relative risk (risk ratio) for dichotomous data and mean
      difference (MD) for continuous data, with 95% confidence intervals. We planned to
      use the random-effects statistical model when the estimate effects of two or more
      studies could be combined in a meta-analysis. MAIN RESULTS: Our search strategy
      retrieved 493 studies. No published RCTs testing de-escalation of antimicrobial
      treatment for adult patients diagnosed with sepsis, severe sepsis or septic were
      included in this review. We found one ongoing RCT. AUTHORS' CONCLUSIONS: There is
      no adequate, direct evidence as to whether de-escalation of antimicrobial agents
      is effective and safe for adults with sepsis, severe sepsis or septic shock. This
      uncertainty warrants further research via RCTs and the authors are awaiting the
      results of an ongoing RCT testing the de-escalation of empirical antimicrobial
      therapy for severe sepsis.

PMID- 23543558
TI  - Oxcarbazepine for neuropathic pain.
AB  - BACKGROUND: Neuropathic pain is difficult to treat. Oxcarbazepine is an
      anticonvulsant drug closely related to carbamazepine and is reportedly better
      tolerated. Oxcarbazepine has been reported to be efficacious in the treatment of
      neuropathic pain. OBJECTIVES: To determine the benefits and harms of
      oxcarbazepine for different forms of neuropathic pain. SEARCH METHODS: We
      searched the Cochrane Neuromuscular Disease Group Specialized Register (30
      October 2012), CENTRAL (2012, Issue 10), MEDLINE (January 1966 to October 2012),
      EMBASE (January 1980 to October 2012) and the Chinese Biomedical Retrieval System
      (January 1978 to October 2012) for trials. We also searched the National
      Institutes of Health (NIH) databases and the World Health Organization (WHO)
      International Clinical Trials Registry Platform for ongoing trials, and wrote to
      the companies who make oxcarbazepine and to pain experts asking for additional
      information. SELECTION CRITERIA: All randomised controlled trials and cross-over
      studies of oxcarbazepine for the treatment of people of any age or sex with any
      neuropathic pain were eligible. We planned to include trials of oxcarbazepine
      compared with placebo or any other intervention, regardless of administration
      route, dosage or length of treatment. DATA COLLECTION AND ANALYSIS: Two review
      authors independently selected the studies for inclusion, assessed their risk of
      bias, extracted data and typed the data onto forms. The authors resolved any
      disagreements through discussion. MAIN RESULTS: Four multicentre, randomised,
      placebo-controlled, double-blind trials with a total of 779 participants were
      eligible for inclusion. These were from a series of studies funded by the
      manufacturer. Three of them investigated oxcarbazepine in people with painful
      diabetic neuropathy (634 participants) and one was a trial of oxcarbazepine for
      neuropathic pain due to radiculopathy (145 participants). Although these trials
      were well designed, the imbalanced and large amount of incomplete outcome data
      led to a risk of bias in the results. Results for painful diabetic neuropathy
      showed that compared to the baseline the proportion of participants who reported
      a 50% or 30% reduction of pain scores after 16 weeks of treatment was
      significantly higher in the oxcarbazepine group than the placebo group (50%
      reduction: risk ratio (RR) 1.91, 95% confidence interval (CI) 1.08 to 3.39,
      number of people needed to treat for an additional beneficial outcome (NNTB) 6.0,
      95% CI 3.3 to 41.0; 30% reduction: RR 1.57, 95% CI 1.01 to 2.44, NNTB 6.1, 95% CI
      3.1 to 113.6). However, both results were based on data from the single positive
      trial (146 participants) since the two negative trials did not provide data that
      could be included in a meta-analysis. For participants with neuropathic pain due
      to radiculopathy, the trial demonstrated no significant efficacy for
      oxcarbazepine. Although trial reports stated that most side effects were mild to
      moderate in severity, the proportion of events leading to withdrawals was
      statistically higher in the oxcarbazepine group than in the placebo group both
      for painful diabetic neuropathy (RR 3.86, 95% CI 2.29 to 6.40) and radiculopathy
      (RR 2.84, 95% CI 1.55 to 5.23). AUTHORS' CONCLUSIONS: On the basis of moderate
      quality evidence from one trial in diabetic peripheral neuropathy, oxcarbazepine
      is effective in reducing pain for this condition. However, this conclusion does
      not take into account negative results from other trials in diabetic peripheral
      neuropathy that could not be included in our meta-analysis. We did not find any
      evidence from randomised controlled trials to determine the efficacy or safety of
      oxcarbazepine for other kinds of neuropathic pain. Most adverse effects related
      to oxcarbazepine are rated as mild to moderate in severity, but adverse events
      leading to discontinuation of drug administration or serious adverse events are
      not uncommon. More well designed randomised controlled trials investigating
      oxcarbazepine for various types of neuropathic pain are needed.

PMID- 23543559
TI  - Human papillomavirus testing versus repeat cytology for triage of minor
      cytological cervical lesions.
AB  - BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) and low
      grade squamous intra-epithelial lesions (LSIL) are minor lesions of the cervical
      epithelium, detectable by cytological examination of cells collected from the
      surface of the cervix of a woman.Usually, women with ASCUS and LSIL do not have
      cervical (pre-) cancer, however a substantial proportion of them do have
      underlying high-grade cervical intra-epithelial neoplasia (CIN, grade 2 or 3) and
      so are at increased risk for developing cervical cancer. Therefore, accurate
      triage of women with ASCUS or LSIL is required to identify those who need further
      management.This review evaluates two ways to triage women with ASCUS or LSIL:
      repeating the cytological test, and DNA testing for high-risk types of the human
      papillomavirus (hrHPV) - the main causal factor of cervical cancer. OBJECTIVES:
      Main objective To compare the accuracy of hrHPV testing with the Hybrid Capture 2
      (HC2) assay against that of repeat cytology for detection of underlying cervical
      intraepithelial neoplasia of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+)
      in women with ASCUS or LSIL. For the HC2 assay, a positive result was defined as
      proposed by the manufacturer. For repeat cytology, different cut-offs were used
      to define positivity: Atypical squamous cells of undetermined significance or
      worse (ASCUS+), low-grade squamous intra-epithelial lesions or worse (LSIL+) or
      high-grade squamous intra-epithelial lesions or worse (HSIL+).Secondary objective
      To assess the accuracy of the HC2 assay to detect CIN2+ or CIN3+ in women with
      ASCUS or LSIL in a larger group of reports of studies that applied hrHPV testing
      and the reference standard (coloscopy and biopsy), irrespective whether or not
      repeat cytology was done. SEARCH METHODS: We made a comprehensive literature
      search that included the Cochrane Register of Diagnostic Test Accuracy Studies;
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library), MEDLINE (through PubMed), and EMBASE (last search 6 January 2011).
      Selected journals likely to contain relevant papers were handsearched from 1992
      to 2010 (December). We also searched CERVIX, the bibliographic database of the
      Unit of Cancer Epidemiology at the Scientific Institute of Public Health
      (Brussels, Belgium) which contains more than 20,000 references on cervical
      cancer.More recent searches, up to December 2012, targeted reports on the
      accuracy of triage of ASCUS or LSIL with other HPV DNA assays, or HPV RNA assays
      and other molecular markers. These searches will be used for new Cochrane reviews
      as well as for updates of the current review. SELECTION CRITERIA: Studies
      eligible for inclusion in the review had to include: women presenting with a
      cervical cytology result of ASCUS or LSIL, who had undergone both HC2 testing and
      repeat cytology, or HC2 testing alone, and were subsequently subjected to
      reference standard verification with colposcopy and colposcopy-directed biopsies
      for histologic verification. DATA COLLECTION AND ANALYSIS: The review authors
      independently extracted data from the selected studies, and obtained additional
      data from report authors.Two groups of meta-analyses were performed: group I
      concerned triage of women with ASCUS, group II concerned women with LSIL. The
      bivariate model (METADAS-macro in SAS) was used to assess the absolute accuracy
      of the triage tests in both groups as well as the differences in accuracy between
      the triage tests. MAIN RESULTS: The pooled sensitivity of HC2 was significantly
      higher than that of repeat cytology at cut-off ASCUS+ to detect CIN2+ in both
      triage of ASCUS and LSIL (relative sensitivity of 1.27 (95% CI 1.16 to 1.39; P
      value < 0.0001) and 1.23 (95% CI 1.06 to 1.4; P value 0.007), respectively. In
      ASCUS triage, the pooled specificity of the triage methods did not differ
      significantly from each other (relative specificity: 0.99 (95% CI 0.97 to 1.03; P
      value 0.98)). However, the specificity of HC2 was substantially, and
      significantly, lower than that of repeat cytology in the triage of LSIL (relative
      specificity: 0.66 (95% CI 0.58 to 0.75) P value < 0.0001). AUTHORS' CONCLUSIONS:
      HPV-triage with HC2 can be recommended to triage women with ASCUS because it has
      higher accuracy (significantly higher sensitivity, and similar specificity) than
      repeat cytology. When triaging women with LSIL, an HC2 test yields a
      significantly higher sensitivity, but a significantly lower specificity, compared
      to a repeat cytology. Therefore, practice recommendations for management of women
      with LSIL should be balanced, taking local circumstances into account.

PMID- 23543560
TI  - Anti-TNF-alpha treatment for pelvic pain associated with endometriosis.
AB  - BACKGROUND: Endometriosis is a chronic, recurring condition that can develop
      during the reproductive years. It is characterised by the development of
      endometrial tissue outside the uterine cavity. It is the most common cause of
      pelvic pain in women. This endometrial tissue development is dependent on
      oestrogen produced primarily by the ovaries and, therefore, traditional
      management has focused on suppression of ovarian function. Mounting evidence
      shows that altered immune function plays a crucial role in the genesis and
      development of endometriosis. In this review we considered modulation of the
      inflammation as an alternative approach. OBJECTIVES: To determine the
      effectiveness and safety of anti-tumour necrosis factor-alpha (anti-TNF-alpha)
      treatment in the management of endometriosis in premenopausal women. SEARCH
      METHODS: For the first publication of this review, we searched for trials in the
      following databases (from their inception to August 2009): Cochrane Menstrual
      Disorders and Subfertility Group Specialised Register, Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL,
      and PsycINFO. In addition, we searched all reference lists of included trials and
      contacted experts in the field in an attempt to locate trials. We reran this
      search to 3 September 2012 for this update. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) comparing anti-TNF-alpha drugs with placebo, no
      treatment, medical treatment, or surgery for pelvic pain associated with
      endometriosis were included. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected trials for inclusion, assessed trial quality, and
      extracted data using data extraction forms. The domains assessed for risk of bias
      were sequence generation, allocation concealment, blinding, incomplete outcome
      data, and selective outcome reporting. We used risk ratios (RR) for reporting
      dichotomous data with 95% confidence intervals (CI), whilst we expressed
      continuous data as mean differences (MD). We assessed statistical heterogeneity
      using the I(2) statistic. MAIN RESULTS: Only one trial involving 21 participants
      was included. The results showed no evidence of an effect of infliximab, one of
      the known anti-TNF-alpha drugs, on pelvic pain reduction using the Biberoglu
      Behrman (BB) score (0 to 3 scale) for participants (MD -0.14, 95% CI -0.43 to
      0.15), the BB score for clinicians (MD -0.14, 95% CI -0.39 to 0.11), or a visual
      analogue pain score (VAS, 100 mm scale) (MD -5.60, 95% CI -16.10 to 4.90), or on
      the use of pain killers (ibuprofen, g/day) (MD -0.10, 95% CI -0.30 to 0.10).
      There was no evidence of an increase in adverse events in the infliximab group
      compared with placebo (RR 3.73, 95% CI 0.22 to 63.66). We found no evidence of
      clinical benefits of infliximab for endometriotic lesions, dysmenorrhoea,
      dyspareunia, or pelvic tenderness. To date, there is no trial that has reported a
      cost-effectiveness analysis of anti-TNF-alpha drugs, or the odds of recurrence.
      AUTHORS' CONCLUSIONS: This review was updated in 2012. The results of the
      original review published in 2010 remain unchanged. There is still not enough
      evidence to support the use of anti-TNF-alpha drugs in the management of women
      with endometriosis for the relief of pelvic pain.

PMID- 23543561
TI  - Pre-treatment surgical para-aortic lymph node assessment in locally advanced
      cervical cancer.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in The Cochrane Library, Issue 4, 2011.Cervical cancer is the most common cause
      of death from gynaecological cancers worldwide. Locally advanced cervical cancer,
      FIGO stage (International Federation of Gynaecology and Obstetrics) equal or more
      than IB1 is treated with chemotherapy and external beam radiotherapy followed by
      brachytherapy. If there is metastatic para-aortic nodal disease, radiotherapy is
      extended to cover this area. Due to increased morbidity, ideally extended-field
      radiotherapy is given only when para-aortic nodal disease is confirmed.
      Therefore, accurate assessment of the extent of the disease is very important for
      planning the most appropriate treatment. OBJECTIVES: To evaluate the
      effectiveness and safety of pre-treatment surgical para-aortic lymph node
      assessment for woman with locally advanced cervical cancer (FIGO stage IB2 to
      IVA). SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials
      Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, 2012, Issue 10), MEDLINE and EMBASE (up to November 2012). We also
      searched registers of clinical trials, abstracts of scientific meetings,
      reference lists of included studies and contacted experts in the field. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) that compared surgical para-aortic
      lymph node assessment and dissection with radiological staging techniques, in
      adult women diagnosed with locally advanced cervical cancer. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed whether potentially relevant
      trials met the inclusion criteria, abstracted data and assessed risk of bias. One
      RCT was identified so no meta-analyses were performed. MAIN RESULTS: We found
      only one trial, which included 61 women, that met our inclusion criteria. This
      trial reported data on surgical versus clinical staging and an assessment of the
      two surgical staging techniques; laparoscopic (LAP) versus extraperitoneal (EXP)
      surgical staging. The clinical staging was either a contrast-enhanced computed
      tomography (CT) scan or magnetic resonance imaging (MRI) scan of the abdomen and
      pelvis to determine nodal status.In this trial, clinical staging appeared to
      significantly prolong overall and progression-free survival compared to surgical
      staging. There was no statistically significant difference in the number of women
      who experienced severe (grade 3 or 4) toxicity.There was no statistically
      significant difference in the risk of death, disease recurrence or progression,
      blood loss, severe toxicity and the duration of the operational procedure between
      LAP and EXP surgical staging techniques.The strength of the evidence is weak in
      this review as it is based on one small trial that was at moderate risk of bias.
      AUTHORS' CONCLUSIONS: Since the last version of this review no new studies were
      found.From the one available RCT we found insufficient evidence that pre
      treatment surgical para-aortic lymph node assessment for locally advanced
      cervical cancer is beneficial, and it may actually have an adverse effect on
      survival. However, this conclusion is based on analysis of a small single trial
      and therefore definitive guidance or recommendations for clinical practice cannot
      be made.Therefore, the decision to offer surgical pre-treatment assessment of
      para-aortic lymph nodes in locally advanced cervical cancer needs to be
      individualised. The uncertainty regarding any impact on survival from pre
      treatment para-aortic lymph node assessment should be discussed openly with the
      women.

PMID- 23543562
TI  - Thromboprophylaxis for trauma patients.
AB  - BACKGROUND: Trauma is a leading causes of death and disability in young people.
      Venous thromboembolism (VTE) is a principal cause of death. Trauma patients are
      at high risk of deep vein thrombosis (DVT). The incidence varies according to the
      method used to measure the DVT and the location of the thrombosis. Due to
      prolonged rest and coagulation abnormalities, trauma patients are at increased
      risk of thrombus formation. Thromboprohylaxis, either mechanical or
      pharmacological, may decrease mortality and morbidity in trauma patients who
      survive beyond the first day in hospital, by decreasing the risk of VTE in this
      population.A previous systematic review did not find evidence of effectiveness
      for either pharmacological or mechanical interventions. However, this systematic
      review was conducted 10 years ago and most of the included studies were of poor
      quality. Since then new trials have been conducted. Although current guidelines
      recommend the use of thromboprophylaxis in trauma patients, there has not been a
      comprehensive and updated systematic review since the one published. OBJECTIVES:
      To assess the effects of thromboprophylaxis in trauma patients on mortality and
      incidence of deep vein thrombosis and pulmonary embolism. To compare the effects
      of different thromboprophylaxis interventions and their effects according to the
      type of trauma. SEARCH METHODS: We searched The Cochrane Injuries Group
      Specialised Register (searched April 30 2009), Cochrane Central Register of
      Controlled Trials 2009, issue 2 (The Cochrane Library), MEDLINE (Ovid) 1950 to
      April (week 3) 2009, EMBASE (Ovid) 1980 to (week 17) April 2009, PubMed (searched
      29 April 2009), ISI Web of Science: Science Citation Index Expanded (SCI
      EXPANDED) (1970 to April 2009), ISI Web of Science: Conference Proceedings
      Citation Index-Science (CPCI-S) (1990 to April 2009). SELECTION CRITERIA:
      Randomized controlled clinical trials involving people of any age with major
      trauma defined by one or more of the following criteria: physiological:
      penetrating or blunt trauma with more than two organs and unstable vital signs,
      anatomical: people with an Injury Severity Score (ISS) higher than 9, mechanism:
      people who are involved in a 'high energy' event with a risk for severe injury
      despite stable or normal vital signs. We excluded trials that only recruited
      outpatients, trials that recruited people with hip fractures only, or people with
      acute spinal injuries. DATA COLLECTION AND ANALYSIS: Four authors, in pairs (LB
      and CM, EF and RC), independently examined the titles and the abstracts,
      extracted data, assessed the risk of bias of the trials and analysed the data. PP
      resolved any disagreement between the authors. MAIN RESULTS: Sixteen studies were
      included (n=3005). Four trials compared the effect of any type (mechanical and/or
      pharmacological) of prophylaxis versus no prophylaxis. Prophylaxis reduced the
      risk of DVT in people with trauma (RR 0.52; 95% CI 0.32 to 0.84). Mechanical
      prophylaxis reduced the risk of DVT (RR = 0.43; 95% CI 0.25 to 0.73).
      Pharmacological prophylaxis was more effective than mechanical methods at
      reducing the risk of DVT (RR 0.48; 95% CI 0.25 to 0.95). LMWH appeared to reduce
      the risk of DVT compared to UH (RR 0.68; 95% CI 0.50 to 0.94). People who
      received both mechanical and pharmacological prophylaxis had a lower risk of DVT
      (RR 0.34; 95% CI 0.19 to 0.60) AUTHORS' CONCLUSIONS: We did not find evidence
      that thromboprophylaxis reduces mortality or PE in any of the comparisons
      assessed. However, we found some evidence that thromboprophylaxis prevents DVT.
      Although the strength of the evidence was not high, taking into account existing
      information from other related conditions such as surgery, we recommend the use
      of any DVT prophylactic method for people with severe trauma.

PMID- 23543563
TI  - Stent graft types for endovascular repair of abdominal aortic aneurysms.
AB  - BACKGROUND: The UK prevalence of abdominal aortic aneurysm (AAA) is estimated at
      4.9% in over 65-year olds. Progressive and unpredictable enlargement can lead to
      rupture. Endovascular repair of AAAs involves a stent graft system being
      introduced via the femoral artery and manipulated within the aorta under
      radiological guidance. Following endograft deployment, a seal is formed at the
      proximal and distal landing zones to exclude the aneurysm sac from the
      circulation. With the increasing popularity of endovascular repair there has been
      an increase in the number of commercially available stent graft designs on the
      market. OBJECTIVES: This review aimed to assess the different stent graft types
      for endovascular repair of AAA. SEARCH METHODS: The Cochrane Peripheral Vascular
      Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register
      (last searched November 2012) and CENTRAL (2012, Issue 10). Trial databases were
      searched by the TSC for details of ongoing and unpublished studies. SELECTION
      CRITERIA: All published and unpublished randomised controlled trials (RCTs) of
      stent graft types in the repair of AAAs were sought without language restriction
      and in consultation with the Peripheral Vascular Disease Group TSC. DATA
      COLLECTION AND ANALYSIS: We planned to conduct data collection and analysis in
      accordance with the Cochrane Handbook for Systematic Reviews of Interventions.
      MAIN RESULTS: No studies were identified that met the inclusion criteria.
      AUTHORS' CONCLUSIONS: Unfortunately, no data exist regarding direct comparisons
      of the performance of different stent graft types. Therefore, this review cannot
      recommend guidance to clinicians in their selection of stent graft types. High
      quality randomised controlled trials evaluating stent graft types in abdominal
      endovascular aneurysm repair are required.

PMID- 23543564
TI  - Stent graft types for endovascular repair of thoracic aortic aneurysms.
AB  - BACKGROUND: The UK prevalence of thoracic aneurysm is estimated at 10.4 per
      100,000 person-years. Progressive and unpredictable enlargement can lead to
      rupture. Endovascular repair of thoracic aortic aneurysms involves a stent graft
      system being introduced via the femoral artery and manipulated within the aorta
      under radiological guidance. Following endograft deployment, a seal is formed at
      the proximal and distal landing zones to exclude the aneurysm sac from the
      circulation. With the increasing popularity of endovascular repair there has been
      an increase in the number of commercially available stent graft designs on the
      market. OBJECTIVES: This review aimed to assess the different stent graft types
      for endovascular repair of thoracic aortic aneurysms. SEARCH METHODS: The
      Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC)
      searched the Specialised Register (last searched November 2012) and CENTRAL
      (2012, Issue 11). Trial databases were searched by the TSC for details of ongoing
      and unpublished studies. SELECTION CRITERIA: All published and unpublished
      randomised controlled trials (RCTs) of stent graft types in the repair of
      thoracic aortic aneurysms were sought without language restriction. DATA
      COLLECTION AND ANALYSIS: Data collection and analysis was conducted in accordance
      with the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS:
      No studies were identified that met the inclusion criteria. AUTHORS' CONCLUSIONS:
      Unfortunately, no data exist regarding direct comparisons of the performance of
      different stent graft types. Therefore, this review cannot recommend guidance to
      clinicians in their selection of stent graft types. High quality RCTs evaluating
      stent graft types in thoracic endovascular aneurysm repair are required.

PMID- 23543565
TI  - Continuous versus intermittent infusions of antibiotics for the treatment of
      severe acute infections.
AB  - BACKGROUND: Intravenous broad-spectrum antibiotics are indicated for the
      treatment of severe infections. However, the emergence of infections caused by
      multi-drug resistant organisms in conjunction with a lack of novel antibiotics
      has prompted the investigation of alternative dosing strategies to improve
      clinical efficacy and tolerability. To optimise pharmacokinetic and
      pharmacodynamic antibiotic parameters, continuous antibiotic infusions have been
      compared to traditional intermittent antibiotic infusions. OBJECTIVES: To compare
      the clinical efficacy and safety of continuous intravenous administration of
      concentration-dependent and time-dependent antibiotics to traditional
      intermittent intravenous administration in adults with severe acute bacterial
      infections. SEARCH METHODS: The following electronic databases were searched in
      September 2012: The Cochrane Injuries Group Specialised Register, Cochrane
      Central Register of Controlled Trials (The Cochrane Library), MEDLINE (OvidSP),
      EMBASE (OvidSP), CINAHL, ISI Web of Science: Science Citation Index Expanded (SCI
      EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science
      (CPCI-S). The reference lists of all relevant material, the Internet and the
      trials registry www.clinicaltrials.gov for completed and ongoing trials were also
      searched. SELECTION CRITERIA: Randomized controlled trials in adults with a
      bacterial infection requiring intravenous antibiotic therapy comparing continuous
      versus intermittent infusions of antibiotics were included. Both time-dependent
      and concentration-dependent antibiotics were considered. DATA COLLECTION AND
      ANALYSIS: Three independent authors performed data extraction for the included
      studies. All data was cross-checked and disagreements resolved by consensus. An
      intention to treat analysis was conducted using a random-effects model. MAIN
      RESULTS: Twenty-nine studies met inclusion criteria with a combined total of over
      1,600 patients. The majority of included studies were judged to be at unclear or
      high risk of bias with regard to randomisation sequence generation, allocation
      concealment, blinding, management of incomplete outcome data, selective outcome
      reporting, and other potential threats to validity. No studies were judged to be
      at low risk of bias for all methodological quality items assessed. There were no
      differences in all-cause mortality (n=1241, RR 0.89, 95% CI 0.67 - 1.20, p=0.45),
      infection recurrence (n=398, RR 1.22, 95% CI 0.35 - 4.19, p=0.76), clinical cure
      (n=975, RR 1.00, 95% CI 0.93 - 1.08, p=0.98), and superinfection post-therapy
      (n=813, RR 1.08, 95% CI 0.60 - 1.94, p=0.79). There were no differences in safety
      outcomes including adverse events (n=575, RR 1.02, 95% CI 0.94 - 1.12, p=0.63),
      serious adverse events (n=871, RR 1.36, 95% CI 0.80 - 2.30, p=0.26), and
      withdrawal due to adverse events (n=871, RR 2.03, 95% CI 0.52 - 7.95, p=0.31). A
      difference was observed in the subgroup analyses of clinical cure in septic
      versus non-septic patients, where intermittent antibiotic infusions were favoured
      for clinical cure in septic patients. However, this effect was not consistent
      between random-effects and fixed-effects analyses. No differences were found in
      sensitivity analyses conducted. AUTHORS' CONCLUSIONS: There were no differences
      in mortality, infection recurrence, clinical cure, superinfection post-therapy,
      and safety outcomes when comparing continuous infusions of intravenous
      antibiotics to traditional intermittent infusions of antibiotics. However, the
      wide confidence intervals suggest that beneficial or harmful effects cannot be
      ruled out for all outcomes. Therefore, the current evidence is insufficient to
      recommend the widespread adoption of continuous infusion antibiotics in the place
      of intermittent infusions of antibiotics. Further large prospective randomised
      trials, with consistent and complete reporting of clinical outcome measures,
      conducted with concurrent pharmacokinetic and pharmacodynamic studies in special
      populations are required to determine whether adoption of continuous antibiotic
      infusions is warranted in specific circumstances.

PMID- 23543566
TI  - Non-pharmacological interventions for preventing secondary vascular events after
      stroke or transient ischemic attack.
AB  - BACKGROUND: Stroke is the second leading cause of death among adults worldwide.
      Individuals who have suffered a stroke are at high risk of having another stroke
      likely leading to greater disability and institutionalization. Non
      pharmacological interventions may have a role to play in averting a second
      stroke. OBJECTIVES: To determine the effectiveness of multi-modal programs of non
      pharmacological interventions compared with usual care in preventing secondary
      vascular events and reducing vascular risk factors after stroke or transient
      ischemic attack (TIA). SEARCH METHODS: We searched the Cochrane Stroke Group
      Trials Register (September 2012); The Cochrane Library databases CENTRAL, CDSR,
      DARE, HTA and NHS EED (2012 Issue 2); MEDLINE (1950 to February 2012); EMBASE
      (1974 to February 2012); CINAHL (1982 to February 2012); SPORTDiscus (1800 to
      February 2012); PsycINFO (1887 to February 2012) and Web of Science (1900 to
      February 2012). We also searched PEDro, OT Seeker, OpenSIGLE, REHABDATA and
      Dissertation Abstracts (February 2012). In an effort to identify further
      published, unpublished and ongoing trials we searched trials registers, scanned
      reference lists, and contacted authors and researchers. SELECTION CRITERIA: We
      included randomized controlled trials evaluating the use of non-pharmacological
      interventions that included components traditionally used in cardiac
      rehabilitation (CR) programs in adults with stroke or TIA. Primary outcomes were
      a cluster of second stroke or myocardial infarction or vascular death. Secondary
      outcomes were (1) secondary vascular events: second stroke, myocardial
      infarction, and vascular death, as well as (2) vascular risk factors: blood
      pressure, body weight, lipid profile, insulin resistance and tobacco use. We also
      recorded adverse events such as exercise-related musculoskeletal injuries or
      cardiovascular events. DATA COLLECTION AND ANALYSIS: Two review authors
      independently scanned titles and abstracts and independently screened full
      reports of studies that were potentially relevant. At each stage, we compared
      results. The two review authors resolved disagreements through discussion or by
      involving a third review author. MAIN RESULTS: We identified one study, involving
      48 participants, of a 10-week CR program for patients post-stroke that met the
      inclusion criteria. The results of this completed pilot trial show that patients
      post-stroke had significantly greater improvement in cardiac risk score in the CR
      group (13.4 +/- 10.1 to 12.4 +/- 10.5, P value < 0.05) when compared with usual
      care (9.4 +/- 6.7 to 15.0 +/- 6.1, P value < 0.05). In addition, five trials,
      which are ongoing, will likely meet the inclusion criteria for this review once
      completed. AUTHORS' CONCLUSIONS: There is limited applicable evidence. Therefore,
      no implications for practice can be drawn. Further research is required and
      several trials are underway, the findings of which are anticipated to contribute
      to the body of evidence.

PMID- 23543567
TI  - Computer-based diabetes self-management interventions for adults with type 2
      diabetes mellitus.
AB  - BACKGROUND: Diabetes is one of the commonest chronic medical conditions,
      affecting around 347 million adults worldwide. Structured patient education
      programmes reduce the risk of diabetes-related complications four-fold. Internet
      based self-management programmes have been shown to be effective for a number of
      long-term conditions, but it is unclear what are the essential or effective
      components of such programmes. If computer-based self-management interventions
      improve outcomes in type 2 diabetes, they could potentially provide a cost
      effective option for reducing the burdens placed on patients and healthcare
      systems by this long-term condition. OBJECTIVES: To assess the effects on health
      status and health-related quality of life of computer-based diabetes self
      management interventions for adults with type 2 diabetes mellitus. SEARCH
      METHODS: We searched six electronic bibliographic databases for published
      articles and conference proceedings and three online databases for theses (all up
      to November 2011). Reference lists of relevant reports and reviews were also
      screened. SELECTION CRITERIA: Randomised controlled trials of computer-based self
      management interventions for adults with type 2 diabetes, i.e. computer-based
      software applications that respond to user input and aim to generate tailored
      content to improve one or more self-management domains through feedback, tailored
      advice, reinforcement and rewards, patient decision support, goal setting or
      reminders. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened the abstracts and extracted data. A taxonomy for behaviour change
      techniques was used to describe the active ingredients of the intervention. MAIN
      RESULTS: We identified 16 randomised controlled trials with 3578 participants
      that fitted our inclusion criteria. These studies included a wide spectrum of
      interventions covering clinic-based brief interventions, Internet-based
      interventions that could be used from home and mobile phone-based interventions.
      The mean age of participants was between 46 to 67 years old and mean time since
      diagnosis was 6 to 13 years. The duration of the interventions varied between 1
      to 12 months. There were three reported deaths out of 3578 participants.Computer
      based diabetes self-management interventions currently have limited
      effectiveness. They appear to have small benefits on glycaemic control (pooled
      effect on glycosylated haemoglobin A1c (HbA1c): -2.3 mmol/mol or -0.2% (95%
      confidence interval (CI) -0.4 to -0.1; P = 0.009; 2637 participants; 11 trials).
      The effect size on HbA1c was larger in the mobile phone subgroup (subgroup
      analysis: mean difference in HbA1c -5.5 mmol/mol or -0.5% (95% CI -0.7 to -0.3);
      P < 0.00001; 280 participants; three trials). Current interventions do not show
      adequate evidence for improving depression, health-related quality of life or
      weight. Four (out of 10) interventions showed beneficial effects on lipid
      profile.One participant withdrew because of anxiety but there were no other
      documented adverse effects. Two studies provided limited cost-effectiveness data 
      with one study suggesting costs per patient of less than $140 (in 1997) or 105
      EURO and another study showed no change in health behaviour and resource
      utilisation. AUTHORS' CONCLUSIONS: Computer-based diabetes self-management
      interventions to manage type 2 diabetes appear to have a small beneficial effect
      on blood glucose control and the effect was larger in the mobile phone subgroup.
      There is no evidence to show benefits in other biological outcomes or any
      cognitive, behavioural or emotional outcomes.

PMID- 23543568
TI  - Osmotic therapies added to antibiotics for acute bacterial meningitis.
AB  - BACKGROUND: Every day children and adults throughout the world die from acute
      community-acquired bacterial meningitis, particularly in low-income countries.
      Survivors are at risk of deafness, epilepsy and neurological disabilities.
      Osmotic therapies have been proposed as an adjunct to improve mortality and
      morbidity from bacterial meningitis. The theory is that they will attract extra
      vascular fluid by osmosis and thus reduce cerebral oedema by moving excess water
      from the brain into the blood. The intention is to thus reduce death and improve
      neurological outcomes. OBJECTIVES: To evaluate the effects on mortality, deafness
      and neurological disability of osmotic therapies added to antibiotics for acute
      bacterial meningitis in children and adults. SEARCH METHODS: We searched CENTRAL
      2012, Issue 11, MEDLINE (1950 to November week 3, 2012), EMBASE (1974 to November
      2012), CINAHL (1981 to November 2012), LILACS (1982 to November 2012) and
      registers of ongoing clinical trials (April 2012). We also searched conference
      abstracts and contacted researchers in the field. SELECTION CRITERIA: Randomised
      controlled trials testing any osmotic therapy in adults or children with acute
      bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened the search results and selected trials for inclusion. We
      collected data from each study for mortality, deafness, seizures and neurological
      disabilities. Results are presented using risk ratios (RR) and 95% confidence
      intervals (CI) and grouped according to whether the participants received
      steroids or not. MAIN RESULTS: Four trials were included comprising 1091
      participants. All compared glycerol (a water-soluble sugar alcohol) with a
      control; in three trials this was a placebo, and in one a small amount of 50%
      dextrose. Three trials included comparators of dexamethasone alone or in
      combination with glycerol. As dexamethasone appeared to have no modifying effect,
      we aggregated results across arms where both treatment and control groups
      received corticosteroids and where both treatment and control groups did
      not.Compared to placebo, glycerol may have little or no effect on death in people
      with bacterial meningitis (RR 1.09, 95% confidence interval (CI) 0.89 to 1.33,
      1091 participants, four trials, low-quality evidence); or on death and
      neurological disability combined (RR 1.04, 95% CI 0.86 to 1.25).Glycerol may have
      little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI
      0.90 to 1.30, 909 participants, three trials, low-quality evidence).Glycerol may
      reduce the risk of subsequent deafness (RR 0.60, 95% CI 0.38 to 0.93, 741
      participants, four trials, low-quality evidence). AUTHORS' CONCLUSIONS: The only
      osmotic diuretic to have undergone randomised evaluation is glycerol. Data from
      trials to date have not demonstrated benefit on death, but it may reduce
      deafness. Osmotic diuretics, including glycerol, should not be given to adults
      and children with bacterial meningitis unless as part of carefully conducted
      randomised controlled trial.

PMID- 23543570
TI  - Methods for administering subcutaneous heparin during pregnancy.
AB  - BACKGROUND: Pregnant women with a history of venous thromboembolism (VTE),
      antithrombin deficiency, or other risk factors for VTE, need heparin
      (unfractionated heparin (UFH) or low-molecular weight heparin (LMWH))
      prophylaxis, mainly through administering subcutaneously. Several methods of
      administering heparin (UFH or LMWH) subcutaneously have been introduced to
      prevent adverse pregnant outcomes. The effectiveness and safety of different
      methods administering subcutaneous heparin (UFH or LMWH) during pregnancy have
      not been systematically evaluated. OBJECTIVES: To compare the effectiveness and
      safety of different methods of administering subcutaneous heparin (UFH or LMWH)
      to pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 January 2013) and reference lists of
      retrieved studies. SELECTION CRITERIA: All randomised controlled trials
      (individual and cluster) comparing the effectiveness and safety of different
      methods of administering subcutaneous heparin (UFH or LMWH) during pregnancy.
      Studies reported only as abstracts were eligible for inclusion and would have
      been placed in studies awaiting assessment, pending the full publication of their
      results. Quasi-randomised studies and cross-over trials were not eligible for
      inclusion..Methods of administering subcutaneous heparin include intermittent
      injections versus indwelling catheters or programmable (auto) external infusion
      pumps, or any other devices to facilitate the subcutaneous administration of
      heparin (UFH or LMWH) during pregnancy. DATA COLLECTION AND ANALYSIS: If eligible
      trials had been identified, trial quality would have been assessed and data
      extracted, unblinded by review authors independently. MAIN RESULTS: No trials met
      the inclusion criteria for the review. AUTHORS' CONCLUSIONS: There is no evidence
      from randomised controlled trials to evaluate the effectiveness and safety of
      different methods of administering subcutaneous heparin (UFH or LMWH) to pregnant
      women.

PMID- 23543569
TI  - Pathogen-reduced platelets for the prevention of bleeding.
AB  - BACKGROUND: Platelet transfusions are used to prevent and treat bleeding in
      patients who are thrombocytopenic. Despite improvements in donor screening and
      laboratory testing, a small risk of viral, bacterial or protozoal contamination
      of platelets remains. There is also an ongoing risk from newly emerging blood
      transfusion-transmitted infections (TTIs) for which laboratory tests may not be
      available at the time of initial outbreak.One solution to reduce further the risk
      of TTIs from platelet transfusion is photochemical pathogen reduction, a process
      by which pathogens are either inactivated or significantly depleted in number,
      thereby reducing the chance of transmission. This process might offer additional
      benefits, including platelet shelf-life extension, and negate the requirement for
      gamma-irradiation of platelets. Although current pathogen-reduction technologies
      have been proven significantly to reduce pathogen load in platelet concentrates,
      a number of published clinical studies have raised concerns about the
      effectiveness of pathogen-reduced platelets for post-transfusion platelet
      recovery and the prevention of bleeding when compared with standard platelets.
      OBJECTIVES: To assess the effectiveness of pathogen-reduced platelets for the
      prevention of bleeding in patients requiring platelet transfusions. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL,
      The Cochrane Library 2013, Issue 1), MEDLINE (1950 to 18 February 2013), EMBASE
      (1980 to 18 February 2013), CINAHL (1982 to 18 February 2013) and the Transfusion
      Evidence Library (1980 to 18 February 2013). We also searched several
      international and ongoing trial databases and citation-tracked relevant reference
      lists. We requested information on possible unpublished trials from known
      investigators in the field. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) comparing the transfusion of pathogen-reduced platelets with
      standard platelets. We did not identify any RCTs which compared the transfusion
      of one type of pathogen-reduced platelets with another. DATA COLLECTION AND
      ANALYSIS: One author screened all references, excluding duplicates and those
      clearly irrelevant. Two authors then screened the remaining references, confirmed
      eligibility, extracted data and analysed trial quality independently. We
      requested and obtained a significant amount of missing data from trial authors.
      We performed meta-analyses where appropriate using the fixed-effect model for
      risk ratios (RR) or mean differences (MD), with 95% confidence intervals (95%
      CI), and used the I2 statistic to explore heterogeneity, employing the random
      effects model when I2 was greater than 30%. MAIN RESULTS: We included 10 trials
      comparing pathogen-reduced platelets with standard platelets. Nine trials
      assessed Intercept(r) pathogen-reduced platelets and one trial Mirasol(r)
      pathogen-reduced platelets. Two were randomised cross-over trials and the
      remaining eight were parallel-group RCTs. In total, 1422 participants were
      available for analysis across the 10 trials, of which 675 participants received
      Intercept(r) and 56 Mirasol(r) platelet transfusions. Four trials assessed the
      response to a single study platelet transfusion (all Intercept(r)) and six to
      multiple study transfusions (Intercept(r) (N = 5), Mirasol(r) (N = 1)) compared
      with standard platelets.We found the trials to be generally at low risk of bias
      but heterogeneous regarding the nature of the interventions (platelet
      preparation), protocols for platelet transfusion, definitions of outcomes,
      methods of outcome assessment and duration of follow-up.Our primary outcomes were
      mortality, 'any bleeding', 'clinically significant bleeding' and 'severe
      bleeding', and were grouped by duration of follow-up: short (up to 48 hours),
      medium (48 hours to seven days) or long (more than seven days). Meta-analysis of
      data from five trials of multiple platelet transfusions reporting 'any bleeding'
      over a long follow-up period found an increase in bleeding in those receiving
      pathogen-reduced platelets compared with standard platelets using the fixed
      effect model (RR 1.09, 95% CI 1.02 to 1.15, I2 = 59%); however, this meta
      analysis showed no difference between treatment arms when using the random
      effects model (RR 1.14, 95% CI 0.93 to 1.38).There was no evidence of a
      difference between treatment arms in the number of patients with 'clinically
      significant bleeding' (reported by four out of the same five trials) or 'severe
      bleeding' (reported by all five trials) (respectively, RR 1.06, 95% CI 0.93 to
      1.21, I2 = 2%; RR 1.27, 95% CI 0.76 to 2.12, I2 = 51%). We also found no evidence
      of a difference between treatment arms for all-cause mortality, acute transfusion
      reactions, adverse events, serious adverse events and red cell transfusion
      requirements in the trials which reported on these outcomes. No bacterial
      transfusion-transmitted infections occurred in the six trials that reported this
      outcome.Although the definition of platelet refractoriness differed between
      trials, the relative risk of this event was 2.74 higher following pathogen
      reduced platelet transfusion (RR 2.74, 95% CI 1.84 to 4.07, I2 = 0%).
      Participants required 7% more platelet transfusions following pathogen-reduced
      platelet transfusion when compared with standard platelet transfusion (MD 0.07,
      95% CI 0.03 to 0.11, I2 = 21%), although the interval between platelet
      transfusions was only shown to be significantly shorter following multiple
      Intercept(r) pathogen-reduced platelet transfusion when compared with standard
      platelet transfusion (MD -0.51, 95% CI -0.66 to -0.37, I2 = 0%). In trials of
      multiple pathogen-reduced platelets, our analyses showed the one- and 24-hour
      count and corrected count increments to be significantly inferior to standard
      platelets. However, one-hour increments were similar in trials of single platelet
      transfusions, although the 24-hour count and corrected count increments were
      again significantly lower. AUTHORS' CONCLUSIONS: We found no evidence of a
      difference in mortality, 'clinically significant' or 'severe bleeding',
      transfusion reactions or adverse events between pathogen-reduced and standard
      platelets. For a range of laboratory outcomes the results indicated evidence of
      some benefits for standard platelets over pathogen-reduced platelets. These
      conclusions are based on data from 1422 patients included in 10 trials. Results
      from ongoing or new trials are required to determine if there are clinically
      important differences in bleeding risk between pathogen-reduced platelet
      transfusions and standard platelet transfusions. Given the variability in trial
      design, bleeding assessment and quality of outcome reporting, it is recommended
      that future trials apply standardised approaches to outcome assessment and follow
      up, including safety reporting.

PMID- 23543571
TI  - Vasopressin and its analogues for the treatment of refractory hypotension in
      neonates.
AB  - BACKGROUND: Neonatal hypotension that is refractory to volume expansion,
      catecholamines, or corticosteroids has a mortality of about 50%. Optimization of
      blood pressure and tissue perfusion in refractory hypotension may be crucial to
      improve clinical outcomes. Vasopressin, a neuropeptide hormone, or its analogue
      terlipressin has been used to treat refractory hypotension in neonates and may be
      effective. OBJECTIVES: Our primary objective was to evaluate the efficacy and
      safety of vasopressin and its synthetic analogues (e.g. terlipressin) in
      decreasing mortality and adverse neurodevelopmental outcomes, and improving
      survival in neonates with refractory hypotension. Our secondary objectives were
      to determine the effects of vasopressin and its analogues (terlipressin) on
      improvement in blood pressure, increase in urine output, decrease in inotrope
      score, necrotizing enterocolitis (NEC), periventricular leukomalacia,
      intraventricular hemorrhage, chronic lung disease, and retinopathy of prematurity
      (ROP) in neonates with refractory hypotension. SEARCH METHODS: We searched the
      literature in January 2012, using the search strategy recommended by the Cochrane
      Neonatal Group. We searched electronic databases (CENTRAL (The Cochrane Library),
      MEDLINE, CINAHL, EMBASE), abstracts of the Pediatric Academic Societies, web
      sites for registered trials at www.clinicaltrials.gov and www.controlled
      trials.com and in the reference list of identified articles. SELECTION CRITERIA:
      Randomized or quasi-randomized trials evaluating vasopressin or its analogues, at
      any dosage or duration used as an adjunct to standard therapy (any combination of
      volume expansion, inotropic agents and corticosteroids) to treat refractory
      hypotension in neonates. DATA COLLECTION AND ANALYSIS: We followed the standard
      methods of The Cochrane Collaboration for conducting a systematic review. Two
      review authors (BS and MP) independently assessed the titles and abstracts of
      studies identified by the search strategy for eligibility for inclusion. We
      obtained the full text version if eligibility could not be done reliably by title
      and abstract. We resolved any differences by mutual discussion. We designed
      electronic forms for trial inclusion/exclusion, data extraction, and for
      requesting additional published information from authors of the original reports.
      MAIN RESULTS: Our search did not identify any completed or ongoing trials that
      met our inclusion criteria. Three studies that did not include neonates and one
      study where the objective was not to treat neonates with refractory hypotension
      were excluded. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend
      or refute the use of vasopressin or its analogues in the treatment of refractory
      hypotension in neonates. Well-designed, adequately powered, randomized controlled
      studies are necessary to address efficacy, optimal dosing, safety and long-term
      neurodevelopmental and pulmonary outcomes. 

PMID- 23543572
TI  - Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and
      microalbuminuria in people with sickle cell disease.
AB  - BACKGROUND: Sickle cell disease is a group of disorders characterized by
      deformation of erythrocytes. Renal damage is a frequent complication in sickle
      cell disease as a result of long-standing anemia and disturbed circulation
      through the renal medullary capillaries. Due to the improvement in life
      expectancy of people with sickle cell disease, there has been a corresponding
      significant increase in the incidence of renal complications. Microalbuminuria
      and proteinuria are noted to be a strong predictor of subsequent renal failure.
      There is extensive experience and evidence with angiotensin-converting enzyme
      (ACE) inhibitors over many years in a variety of clinical situations for patients
      who do not have sickle cell disease, but their effect in patients with this
      disease is unknown. It is common practice to administer ACE inhibitors for sickle
      nephropathy due to their renoprotective properties; however, little is known
      about their effectiveness and safety in this setting. OBJECTIVES: To determine
      the effectiveness of ACE inhibitor administration in people with sickle cell
      disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria
      and to to assess the safety of ACE inhibitors as pertains to their adverse
      effects. SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group's Hameoglobinopathies Trials Register comprising
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference
      proceedings.Date of the most recent search: 05 July 2012. SELECTION CRITERIA:
      Randomized or quasi-randomized controlled trials of ACE inhibitors designed to
      reduce microalbuminuria and proteinuria in people with sickle cell disease
      compared to either placebo or standard treatment regimen. DATA COLLECTION AND
      ANALYSIS: Three authors independently applied the inclusion criteria in order to
      select studies for inclusion in the review. Two authors assessed the risk of bias
      of studies and extracted data and the third author verified these assessments.
      MAIN RESULTS: Five studies were identified through the searches, only one met our
      inclusion criteria. The included study randomized 22 participants (7 males and 15
      females) having proteinuria or microalbuminuria with sickle cell disease and
      treated the participants for six months (median length of follow-up of three
      months) with captopril or placebo. At six months, the study reported no
      significant difference in urinary albumin excretion between the captopril group
      and the placebo group, although the mean urinary albumin excretion in the
      captopril group was lower by a mean difference of -49.00 (95% confidence interval
      -124.10 to 26.10) compared to that of placebo. However, our analysis on the
      absolute change score showed significant changes between the two groups by a mean
      difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months
      albumin excretion in the captopril group was noted to decrease from baseline by a
      mean of 45 +/- 23 mg/day and the placebo group was noted to increase by 18 +/- 45
      mg/day. Serum creatinine and potassium levels were reported constant throughout
      the study. The potential for inducing hypotension should be highlighted; the
      study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic
      and mean blood pressure. AUTHORS' CONCLUSIONS: There is not enough evidence to
      show that the administration of ACE inhibitors is associated with a reduction of
      microalbuminuria and proteinuria in people with sickle cell disease, although a
      potential for this was seen. More long-term studies involving multiple centers
      and larger cohorts using a randomized-controlled design are warranted, especially
      among the pediatric age group. Detailed reporting of each outcome measure is
      necessary to allow a clear cut interpretation in a systematic review. One of the
      difficulties encountered in this review was the lack of detailed data reported in
      the included study.

PMID- 23543573
TI  - Helicopter emergency medical services for adults with major trauma.
AB  - BACKGROUND: Although helicopters are presently an integral part of trauma systems
      in most developed nations, previous reviews and studies to date have raised
      questions about which groups of traumatically injured patients derive the
      greatest benefit. OBJECTIVES: The purpose of this review is to determine if
      helicopter emergency medical services transport (HEMS) is associated with
      improved morbidity and mortality, compared to ground emergency medical services
      transport (GEMS), for adults with major trauma. The primary outcome was survival
      to hospital discharge. Secondary outcomes were quality-adjusted life years
      (QALYs) and disability-adjusted life years (DALYs). SEARCH METHODS: Searches were
      run in CENTRAL, MEDLINE, EMBASE, CINAHL (EBSCOhost), SCI-EXPANDED, CPCI-S, and
      ZETOC in January 2012. Relevant websites were also searched, including controlled
      trials registers, HSRProj, the World Health Organization (WHO) ICTRP, and
      OpenSIGLE. Searches were not restricted by date, language, or publication status.
      Attempts were made to contact authors in the case of missing data. SELECTION
      CRITERIA: Eligible trials included randomised controlled trials (RCTs) and non
      randomised intervention studies. Non-randomised studies (NRS), including
      controlled trials and cohort studies, were also evaluated. Each study was
      required to have a GEMS comparison group. An injury severity score (ISS) > 15 or
      an equivalent marker for injury severity was required. Only adults aged 16 years
      or older were included. DATA COLLECTION AND ANALYSIS: Three review authors
      independently extracted data and assessed the risk of bias of included studies.
      The Downs and Black quality assessment tool was applied for NRS. The results were
      analysed in a narrative review, and with studies grouped by methodology and
      injury type. A predefined subgroup was comprised of four additional studies that
      examined the role of HEMS versus GEMS for inter-facility transfer. Summary of
      findings tables were constructed in accordance with the GRADE Working Group
      criteria. MAIN RESULTS: Twenty-five studies met the entry criteria for this
      review. Four additional studies met the criteria for a separate, predefined
      subgroup analysis of patients transferred to trauma centres by HEMS or GEMS. All
      studies were non-randomised studies; no RCTs were found. Survival at hospital
      discharge was the primary outcome. Data from 163,748 people from 21 of the 25
      studies included in the primary analysis were available to calculate unadjusted
      mortality. Overall, considerable heterogeneity was observed and an accurate
      estimate of overall effect could not be determined. Based on the unadjusted
      mortality data from five trials that focused on traumatic brain injury, there was
      no decreased risk of death with HEMS (relative risk (RR) 1.02; 95% CI 0.85 to
      1.23). Nine studies used multivariate regression to adjust for confounding, the
      five largest indicated a statistically significant increased odds of survival
      associated with HEMS. All Trauma-Related Injury Severity Score (TRISS)-based
      studies indicated improved survival in the HEMS group as compared to the Major
      Trauma Outcomes Study (MTOS) cohort; some studies showed survival benefits in
      both the HEMS and GEMS groups as compared to MTOS. No studies were found to
      evaluate the secondary outcome of morbidity as assessed by QALYs and DALYs. All
      four studies suggested a positive benefit when HEMS was used to transfer patients
      to higher level trauma centres. Overall, the quality of the included studies was
      very low as assessed by the GRADE Working Group criteria. AUTHORS' CONCLUSIONS:
      Due to the methodological weakness of the available literature, and the
      considerable heterogeneity of effects and study methodologies, an accurate
      composite estimate of the benefit of HEMS could not be determined. Although five
      of the nine multivariate regression studies indicated improved survival
      associated with HEMS, the remainder did not. All were subject to a low quality of
      evidence as assessed by the GRADE Working Group criteria due to their non
      randomised design. Similarly, TRISS-based studies, which all demonstrated
      improved survival, cannot be considered strong evidence because of their
      methodology, which did not randomize the use of HEMS. The question of which
      elements of HEMS may be beneficial for patients has not been fully answered. The
      results from this review provide motivation for future work in this area. This
      includes an ongoing need for diligent reporting of research methods, which is
      imperative for transparency and to maximise the potential utility of results.
      Large, multicentre studies are warranted as these will help produce more robust
      estimates of treatment effects. Future work in this area should also examine the
      costs and safety of HEMS, since multiple contextual determinants must be
      considered when evaluating the effects of HEMS for adults with major trauma.

PMID- 23543574
TI  - Different types of dietary advice for women with gestational diabetes mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) affects a significant number of
      women each year and is associated with a wide range of adverse outcomes for women
      and their babies. Dietary counselling is the main strategy in managing GDM, but
      it remains unclear which dietary therapy is best. OBJECTIVES: To assess the
      effects of different types of dietary advice for women with GDM on pregnancy
      outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (17 May 2012) and the WOMBAT Perinatal Trials Registry
      (17 April 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) and
      cluster-RCTs assessing the effects of different types of dietary advice for women
      with GDM on pregnancy outcomes.We intended to compare two or more forms of the
      same type of dietary advice against each other, i.e. standard dietary advice
      compared with individualised dietary advice, individual dietary education
      sessions compared with group dietary education sessions. We intended to compare
      different intensities of dietary intervention with each other, i.e. single
      dietary counselling session compared with multiple dietary counselling sessions.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study
      eligibility, extracted data and assessed risk of bias of included studies. Data
      were checked for accuracy. MAIN RESULTS: We included nine trials; 429 women (436
      babies) provided outcome data. All nine included trials had small sample sizes
      with variation in levels of risk of bias. A total of 11 different types of
      dietary advice were assessed under six different comparisons, including:low
      moderate glycaemic index (GI) food versus high-moderate GI food, low-GI diet
      versus high-fibre moderate-GI diet, energy-restricted diet versus no energy
      restriction diet, low-carbohydrate diet (<= 45% daily total energy intake from
      carbohydrate) versus high-carbohydrate diet (>= 50% daily total energy intake
      from carbohydrate), high-monounsaturated fat diet (at least 20% total energy from
      monounsaturated fat) versus high-carbohydrate diet (at least 50% total energy
      from carbohydrate), standard-fibre diet (American Diabetes Association (ADA)
      diet) (20 grams fibre/day) versus fibre-enriched diet (80 grams fibre/day).In the
      low-moderate GI food versus moderate-high GI food comparison, no significant
      differences were seen for macrosomia or large-for-gestational age (LGA), (two
      trials, 89 babies) (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.10 to
      2.08), (RR 0.95, 95% CI 0.27 to 3.36), respectively; or caesarean section (RR
      0.66, 95% CI 0.29 to 1.47, one trial, 63 women).In the low-GI diet versus high
      fibre moderate-GI diet comparison, no significant differences were seen for
      macrosomia or LGA (one trial, 92 babies) (RR 0.32, 95% CI 0.03 to 2.96), (RR
      2.87, 95% CI 0.61 to 13.50), respectively; or caesarean section (RR 1.80, 95% CI
      0.66 to 4.94, one trial, 88 women).In the energy-restricted versus unrestricted
      diet comparison, no significant differences were seen for macrosomia (RR 1.56,
      95% CI 0.61 to 3.94, one trial, 122 babies); LGA (RR 1.17, 95% CI 0.65 to 2.12,
      one trial, 123 babies); or caesarean section (RR 1.18, 95% CI 0.74 to 1.89, one
      trial, 121 women).In the low- versus high-carbohydrate diet comparison, none of
      the 30 babies in a single trial were macrosomic; and no significant differences
      in caesarean section rates were seen (RR 1.40, 95% CI 0.57 to 3.43, one trial, 30
      women).In the high-monounsaturated fat versus high-carbohydrate diet comparison,
      neither macrosomia or LGA (one trial 27 babies) (RR 0.65, 95% CI 0.91 to 2.18),
      (RR 0.54 95% CI 0.21 to 1.37), respectively showed significant differences. Women
      having a high-monounsaturated fat diet had a significantly higher body mass index
      (BMI) at birth (mean difference (MD) 3.90 kg/m2, 95% CI 2.41 to 5.39, one trial,
      27 women) and at six to nine months postpartum (MD 4.10 kg/m2, 95% CI 2.34 to
      5.86, one trial, 27 women) when compared with those having a high-carbohydrate
      diet. However, these findings were based on a single, small RCT with baseline
      imbalance in maternal BMI.Perinatal mortality was reported in only trial which
      recorded no fetal deaths in either the energy- restricted or unrestricted diet
      group.A single trial comparing ADA diet (20 grams gram fibre/day) with fibre
      enriched fibre enriched diet (80 grams gram fibre/day) did not report any of our
      prespecified primary outcomes.Very limited data were reported on the prespecified
      outcomes for each of the six comparisons. Only one trial reported on early
      postnatal outcomes. No trial reported long-term health outcomes for women and
      their babies. No data were reported on health service cost or women's quality of
      life. AUTHORS' CONCLUSIONS: Data for most comparisons were only available from
      single studies and they are too small for reliable conclusions about which types
      of dietary advice are the most suitable for women with GDM. Based on the current
      available evidence, we did not find any significant benefits of the diets
      investigated.Further larger trials with sufficient power to assess the effects of
      different diets for women with GDM on maternal and infant health outcomes are
      needed. Outcomes such as longer-term health outcomes for women and their babies,
      women's quality of life and health service cost should be included.

PMID- 23543575
TI  - Inhaled corticosteroids for subacute and chronic cough in adults.
AB  - BACKGROUND: Persistent cough is a common clinical problem. Despite thorough
      investigation and empirical management, a considerable proportion of those people
      with subacute and chronic cough have unexplained cough, for which treatment
      options are limited. While current guidelines recommend inhaled corticosteroids
      (ICS), the research evidence for this intervention is conflicting. OBJECTIVES: To
      assess the effects of ICS for subacute and chronic cough in adults. SEARCH
      METHODS: We searched the Cochrane Airways Group Register of Trials, Cochrane
      Central Register of Controlled Trials, MEDLINE, EMBASE and ClinicalTrials.gov in
      December 2012 and conducted handsearches. SELECTION CRITERIA: Two authors
      independently assessed all potentially relevant trials. All published and
      unpublished randomised comparisons of ICS versus placebo in adults with subacute
      or chronic cough were included. Participants with known chronic respiratory
      disease and asthma were excluded. Studies of cough-variant asthma and
      eosinophilic bronchitis were eligible. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data pertaining to pre-defined outcomes. The primary
      outcome was the proportion of participants with clinical cure or significant
      improvement (over 70% reduction in cough severity measure) at follow up (clinical
      success). The secondary outcomes included proportion of participants with
      clinical cure or over 50% reduction in cough severity measure at follow up, mean
      change in cough severity measures, complications of cough, biomarkers of
      inflammation and adverse effects. We requested additional data from study
      authors. MAIN RESULTS: Eight primary studies, including 570 participants, were
      included. The overall methodological quality of studies was good. Significant
      clinical heterogeneity resulting from differences in participants and
      interventions, as well as variation in outcome measures, limited the validity of
      comparisons between studies for most outcomes. Data for the primary outcome of
      clinical cure or significant (> 70%) improvement were available for only three
      studies, which were too heterogeneous to pool. Similarly, heterogeneity in study
      characteristics limited the validity of meta-analysis for the secondary outcomes
      of proportion of participants with clinical cure or over 50% reduction in cough
      severity measure and clinical cure. One parallel group trial of predominantly
      chronic cough with 'cough-variant asthma' identified a significant treatment
      effect and contributed to the majority of statistical heterogeneity for these
      outcomes. While ICS treatment resulted in a mean decrease in cough score of 0.34
      standard deviations (SMD -0.34; 95% CI -0.56 to -0.13; 346 participants), the
      quality of evidence was low. Heterogeneity also prevented meta-analysis for the
      outcome of mean change in visual analogue scale score. Meta-analysis was not
      possible for the outcomes of pulmonary function, complications of cough or
      biomarkers of inflammation due to insufficient data. There was moderate quality
      evidence that treatment with ICS did not significantly increase the odds of
      experiencing an adverse event (OR 1.67; 95% CI 0.92 to 3.04). AUTHORS'
      CONCLUSIONS: The studies were highly heterogeneous and results were inconsistent.
      Heterogeneity in study design needs to be addressed in future research in order
      to test the efficacy of this intervention. International cough guidelines
      recommend that a trial of ICS should only be considered in patients after
      thorough evaluation including chest X-ray and consideration of spirometry and
      other appropriate investigations.

PMID- 23543576
TI  - Subintimal angioplasty for chronic lower limb arterial occlusion.
AB  - BACKGROUND: Subintimal angioplasty (SIA) has become an established percutaneous
      procedure for the treatment of symptomatic lower limb arterial occlusions in
      recent years. However, the clinical benefits of this practice remain unclear. The
      aim of the review was to determine the effectiveness of SIA on clinical outcomes.
      OBJECTIVES: To assess the effectiveness of SIA versus any other treatment for
      patients with chronic lower limb artery occlusion. This will be determined by the
      effects on clinical improvement, technical success rate, patency rate, limb
      salvage rate, and morbidity rates. SEARCH METHODS: The Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised
      Register (last searched January 2013) and CENTRAL (2012, Issue 12). Clinical
      trials databases were also searched. SELECTION CRITERIA: We planned to include
      data from randomized controlled trials comparing the effectiveness of SIA and any
      other management method in the treatment of chronic lower limb arterial
      occlusion. DATA COLLECTION AND ANALYSIS: Two authors evaluated the trials
      identified from the searches for appropriateness of inclusion. MAIN RESULTS:
      There were no randomized controlled trials in which SIA was compared with any
      other treatment. AUTHORS' CONCLUSIONS: Randomized controlled trial evidence for
      the effectiveness of SIA is lacking. There is a need for high-quality randomized
      controlled trials comparing SIA with any other treatment.

PMID- 23543577
TI  - Sulthiame add-on therapy for epilepsy.
AB  - BACKGROUND: Epilepsy is a common neurological condition characterised by
      recurrent seizures. Most patients respond to conventional antiepileptic drugs,
      however, around 30% will continue to experience seizures despite multiple
      antiepileptic drugs. Sulthiame is a widely used antiepileptic drug in Europe and
      Israel. We present a summary of the evidence for the use of sulthiame as add-on
      therapy in epilepsy. OBJECTIVES: To compare the efficacy and side-effect profile
      of sulthiame as add-on therapy compared with placebo or another antiepileptic
      drug. SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialised
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      and the WHO IRCTRP Search Portal on 28th August 2012. No language restrictions
      were imposed. We contacted the manufacturers of sulthiame and researchers in the
      field to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised
      placebo-controlled add-on trials of sulthiame in people of any age with epilepsy
      of any aetiology. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected trials for inclusion and extracted relevant data. The following outcomes
      were assessed: (1) reduction in seizure frequency of 50% or greater between
      baseline and end of follow-up (2) complete cessation of seizures during follow-up
      (3) mean seizure frequency (4) time to treatment withdrawal (5) adverse drug
      effects (6) quality of life scoring. Primary analyses were intention-to-treat.
      Narrative analysis is presented. MAIN RESULTS: One trial was included
      representing 37 patients with a new diagnosis of West syndrome. Sulthiame was
      given as an add-on therapy to pyridoxine. No data were reported for outcomes (1),
      (3) or (6). Overall risk ratio (RR) with 95% confidence intervals (CI) for
      complete cessation of seizures during a nine-day follow-up period versus placebo
      was 0.71 (95% CI 0.53 to 0.96). Meaningful analysis of time to treatment
      withdrawal and adverse drug effects was impossible due to incomplete data.
      AUTHORS' CONCLUSIONS: Sulthiame may lead to a cessation of seizures when used as
      an add-on therapy to pyridoxine in patients with West syndrome. The included
      study was small and had a significant risk of bias which limits the impact of the
      evidence. No conclusions can be drawn on the occurrence of adverse drug effects,
      change in quality of life or mean reduction in seizure frequency. No evidence
      exists for the use of sulthiame as an add-on therapy in patients with epilepsy
      outside West syndrome. Large, multi-centre randomised controlled trials are
      necessary to inform clinical practice if sulthiame is to be used as an add-on
      therapy for epilepsy.

PMID- 23543578
TI  - Effectiveness of the Valsalva Manoeuvre for reversion of supraventricular
      tachycardia.
AB  - BACKGROUND: Patients with the cardiac arrhythmia supraventricular tachycardia
      (SVT) frequently present to clinicians in the prehospital and emergency medicine
      settings. Restoring sinus rhythm by terminating the SVT involves increasing the
      refractoriness of AV nodal tissue within the myocardium by means of vagal
      manoeuvres, pharmacological agents or electrical cardioversion. A commonly used
      first-line technique to restore the normal sinus rhythm (reversion) is the
      Valsalva Manoeuvre (VM). This is a non-invasive means of increasing myocardial
      refractoriness by increasing intrathoracic pressure for a brief period, thus
      stimulating baroreceptor activity in the aortic arch and carotid bodies,
      resulting in increased parasympathetic (vagus nerve) tone. OBJECTIVES: To assess
      the evidence of effectiveness of the Valsalva Manoeuvre in terminating
      supraventricular tachycardia. SEARCH METHODS: We electronically searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library
      (Issue 1 of 12, 2012); MEDLINE Ovid (1946 to January 2012); EMBASE Ovid (1947 to
      January 2012); Web of Science (1970 to 27 January 2012); and BIOSIS Previews
      (1969 to 27 January 2012). Trials registries, the Index to Theses and the
      bibliographies of all relevant publications identified by these strategies were
      also checked. SELECTION CRITERIA: We included all randomised controlled trials
      (RCTs) that examined the effectiveness of the Valsalva Manoeuvre in terminating
      SVT. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data
      using a standardised form. Each trial was assessed for internal validity with
      differences resolved by discussion. Data were then extracted and entered into
      Review Manager 5.1 (RevMan). MAIN RESULTS: We identified three randomised
      controlled trials including 316 participants. All three studies compared the
      effectiveness of VM in reverting SVT with that of other vagal manoeuvres in a
      cross-over design. Two studies induced SVT within a controlled laboratory
      environment. Participants had ceased all medications prior to engaging in these
      studies. The third study reported on patients presenting to a hospital emergency
      department with an episode of SVT. These patients were not controlled for
      medications or other factors prior to intervention.The two laboratory studies
      demonstrated reversion rates of 45.9% and 54.3%, whilst the clinical study
      demonstrated reversion success of 19.4%. This discrepancy may be due to
      methodological differences between studies, the effect of induced SVT versus
      spontaneous episodic SVT, and participant factors such as medications and
      comorbidities. We were unable to assess any of these factors further, nor adverse
      effects, since they were either not described in enough detail or not reported at
      all.Statistical pooling was not possible due to heterogeneity between the
      included studies. AUTHORS' CONCLUSIONS: We did not find sufficient evidence to
      support or refute the effectiveness of the Valsalva Manoeuvre for termination of
      SVT. Further research is needed and this should include a standardised approach
      to performance technique and methodology.

PMID- 23543579
TI  - The role of maintenance therapy in acute promyelocytic leukemia in the first
      complete remission.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is the most curable type of
      leukemia. A consensus exists regarding the need for administration of both
      induction and consolidation treatments, albeit using different approaches.
      However, there is conflicting evidence for the role of maintenance treatment in
      APL patients. OBJECTIVES: To examine the efficacy and safety of maintenance
      therapy in APL patients and to establish the optimal regimen for maintenance.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1966 to July
      2012), LILACS (1982 to July 2012), relevant conference proceedings (2000 to 2012)
      and databases of ongoing and unpublished trials. SELECTION CRITERIA: Randomized
      controlled trials assessing maintenance treatment in patients with newly
      diagnosed APL in first complete remission (CR) following induction or induction
      and consolidation therapy. DATA COLLECTION AND ANALYSIS: Two review authors
      assessed the quality of trials and extracted data. We estimated and pooled hazard
      ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) using the
      fixed-effect model. If significant heterogeneity was present we explored
      potential causes for such heterogeneity and if not found we used also the random
      effects model. MAIN RESULTS: We included 10 randomized controlled trials
      enrolling 2072 patients in the systematic review, and conducted meta-analysis on
      nine of them. There was no statistically significant effect on overall survival
      (OS) in the three main comparisons (HR for any maintenance treatment versus
      observation 0.79, 95% CI 0.49 to 1.27; HR for all-trans retinoic acid (ATRA)
      based maintenance versus non-ATRA based maintenance 1.21, 95% CI 0.73 to 1.98; HR
      for ATRA alone maintenance versus ATRA and chemotherapy 0.99, 95% CI 0.69 to
      1.43). However, disease free survival (DFS) was improved with any maintenance
      therapy compared to observation (HR 0.59, 95% CI 0.48 to 0.74; 5 trials, 1209
      patients) and with ATRA and chemotherapy compared to ATRA alone maintenance (HR
      for ATRA alone compared to ATRA and chemotherapy 1.38, 95% CI 1.09 to 1.76; 4
      trials, 1028 patients). DFS was not improved with ATRA-based regimens compared to
      non-ATRA based regimens (HR 0.72, 95% CI 0.51 to 1.01; 4 trials, 670 patients).
      Analysis of clinically relevant adverse events could not be conducted due to
      paucity of data. Yet, increased reports of grade 3/4 adverse events were noted
      for any maintenance versus observation and for combined ATRA and chemotherapy
      versus ATRA alone treatment. The major limitation of this review lies in the
      variability between the included trials in both maintenance and pre-maintenance
      parameters. We tried to address this variability and to reduce its potential
      biases by conducting three separate main comparisons, as outlined above, leaving
      less statistical power to the presented results. AUTHORS' CONCLUSIONS:
      Maintenance therapy compared to observation in APL patients improved DFS but not
      OS. Similarly, ATRA and chemotherapy compared to ATRA improved DFS but not OS. In
      contrast, ATRA based regimens compared to non-ATRA based regimens did not
      demonstrate a survival benefit. The significance of these findings is limited due
      to clinical heterogeneity between studies.

PMID- 23543580
TI  - Therapeutic ultrasound for carpal tunnel syndrome.
AB  - BACKGROUND: Therapeutic ultrasound may be offered to people experiencing mild to
      moderate symptoms of carpal tunnel syndrome (CTS). The effectiveness and duration
      of benefit of this non-surgical intervention remain unclear. OBJECTIVES: To
      review the effects of therapeutic ultrasound compared with no treatment, placebo
      or another non-surgical intervention in people with CTS. SEARCH METHODS: On 27
      November 2012, we searched the Cochrane Neuromuscular Disease Group Specialized
      Register, CENTRAL (2012, Issue 11 in The Cochrane Library), MEDLINE (January 1966
      to November 2012), EMBASE (January 1980 to November 2012), CINAHL Plus (January
      1937 to November 2012), and AMED (January 1985 to November 2012). SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing any regimen of
      therapeutic ultrasound with no treatment, a placebo or another non-surgical
      intervention in people with CTS. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected trials for inclusion, extracted data and assessed the risk
      of bias in the included studies. We calculated risk ratio (RR) and mean
      difference (MD) with 95% confidence intervals (CIs) for primary and secondary
      outcomes. We pooled results of clinically homogenous trials in a meta-analysis
      using a random-effects model, where possible, to provide estimates of the effect.
      MAIN RESULTS: We included 11 studies including 414 participants in the review.
      Two trials compared therapeutic ultrasound with placebo, two compared one
      ultrasound regimen with another, two compared ultrasound with another non
      surgical intervention, and six compared ultrasound as part of a multi-component
      intervention with another non-surgical intervention (for example, exercises and
      splint). The risk of bias was low in some studies and unclear or high in other
      studies, with only two reporting that the allocation sequence was concealed and
      six reporting that participants were blinded. Overall, there is insufficient
      evidence that one therapeutic ultrasound regimen is more efficacious than
      another. Only two studies reported the primary outcome of interest, short-term
      overall improvement (any measure in which patients indicate the intensity of
      their complaints compared with baseline, for example, global rating of
      improvement, satisfaction with treatment, within three months post-treatment).
      One low quality trial with 68 participants found that when compared with placebo,
      therapeutic ultrasound may increase the chance of experiencing short-term overall
      improvement at the end of seven weeks treatment (RR 2.36; 95% CI 1.40 to 3.98),
      although losses to follow-up and failure to adjust for the correlation between
      wrists in participants with bilateral CTS in this study suggest that this data
      should be interpreted with caution. Another low quality trial with 60
      participants found that at three months post-treatment therapeutic ultrasound
      plus splint increased the chance of short-term overall improvement (patient
      satisfaction) when compared with splint alone (RR 3.02; 95% CI 1.36 to 6.72), but
      decreased the chance of short-term overall improvement when compared with low
      level laser therapy plus splint (RR 0.87; 95% CI 0.57 to 1.33), though
      participants were not blinded to treatment, it was unclear if the random
      allocation sequence was adequately concealed, and there was a potential unit of
      analysis error. Differences between groups receiving different frequencies and
      intensities of ultrasound, and between ultrasound as part of a multi-component
      intervention versus other non-surgical interventions, were generally small and
      not statistically significant for symptoms, function, and neurophysiologic
      parameters. No studies reported any adverse effects of therapeutic ultrasound,
      but this outcome was only measured in three studies. More adverse effects data
      are required before any firm conclusions on the safety of therapeutic ultrasound
      can be made. AUTHORS' CONCLUSIONS: There is only poor quality evidence from very
      limited data to suggest that therapeutic ultrasound may be more effective than
      placebo for either short- or long-term symptom improvement in people with CTS.
      There is insufficient evidence to support the greater benefit of one type of
      therapeutic ultrasound regimen over another or to support the use of therapeutic
      ultrasound as a treatment with greater efficacy compared to other non-surgical
      interventions for CTS, such as splinting, exercises, and oral drugs. More
      methodologically rigorous studies are needed to determine the effectiveness and
      safety of therapeutic ultrasound for CTS.

PMID- 23543581
TI  - Anti-D administration after spontaneous miscarriage for preventing Rhesus
      alloimmunisation.
AB  - BACKGROUND: During pregnancy, a Rhesus-negative (Rh-negative) woman may develop
      antibodies if her fetus is Rh-positive, which can cause fetal morbidity or
      mortality in following pregnancies, if untreated. OBJECTIVES: To assess the
      effects of administering anti-D immunoglobulin (Ig) after spontaneous miscarriage
      in a Rh-negative woman, with no anti-D antibodies. SEARCH METHODS: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2012).
      SELECTION CRITERIA: Randomised controlled trials (RCT) in Rh-negative women
      without antibodies who were given anti-D Ig following spontaneous miscarriage
      compared with no treatment or placebo treatment following spontaneous miscarriage
      as control. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trials for inclusion and trial quality. Two review authors extracted
      data and checked it for accuracy. MAIN RESULTS: We included one RCT, involving 48
      women who had a miscarriage between eight to 24 weeks of gestation. Of the 19
      women in the treatment group, 14 had therapeutic dilatation & curettage (D&C) and
      five had spontaneous miscarriage; of the 29 women in the control group, 25 had
      therapeutic D&C and four had spontaneous miscarriage. The treatment group
      received 300 ug anti-D Ig intramuscular injection and were compared with a
      control group who received 1 cc homogenous gamma globulin placebo.This review's
      primary outcomes (development of a positive Kleihauer Betke test (a test that
      detects fetal cells in the maternal blood; and development of RhD
      alloimmunisation in a subsequent pregnancy) were not reported in the included
      study.Similarly, none of the review's secondary outcomes were reported in the
      included study: the need for increased surveillance for suspected fetal blood
      sampling and fetal transfusions in subsequent pregnancies, neonatal morbidity
      such as neonatal anaemia, jaundice, bilirubin encephalopathy, erythroblastosis,
      prematurity, hypoglycaemia (low blood sugar) in subsequent pregnancies, maternal
      adverse events of anti-D administration including anaphylactic reaction and blood
      borne infections.The included study did report subsequent Rh-positive pregnancies
      in three women in the treatment group and six women in the control group.
      However, due to the small sample size, the study failed to show any difference in
      maternal sensitisation or development of Rh alloimmunisation in the subsequent
      pregnancies. AUTHORS' CONCLUSIONS: There are insufficient data available to
      evaluate the practice of anti-D administration in an unsensitised Rh-negative
      mother after spontaneous miscarriage. Thus, until high-quality evidence becomes
      available, the practice of anti-D Immunoglobulin prophylaxis after spontaneous
      miscarriage for preventing Rh alloimmunisation cannot be generalised and should
      be based on the standard practice guidelines of each country.

PMID- 23543583
TI  - Nidotherapy for people with schizophrenia.
AB  - BACKGROUND: Nidotherapy is a therapeutic method that principally aims to modify
      the environment of people with schizophrenia and other serious mental illnesses,
      whilst working in conjunction with, or alongside other treatments. Rather than
      focusing on direct treatments or interventions, the aim is to help the individual
      identify the need for, and work to effect environmental change with the aim of
      minimising the impact of any form of mental disorder on the individual and
      society. OBJECTIVES: To review the effects of nidotherapy added to standard care,
      compared with standard care or no treatment for people with schizophrenia or
      related disorders. SEARCH METHODS: We searched the Cochrane Schizophrenia Group
      Trials Register (December 2011) and supplemented this by contacting relevant
      study authors, handsearching nidotherapy articles and manually searching
      reference lists. SELECTION CRITERIA: All randomised controlled trials (RCTs) that
      compared nidotherapy with standard care or no treatment. DATA COLLECTION AND
      ANALYSIS: We independently selected and quality assessed potential trials. We
      reliably extracted data. We calculated risk ratios (RR) and 95% confidence
      intervals (CI) of homogeneous dichotomous data. Scale data were only extracted
      from valid scales. For non-skewed continuous endpoint data, we estimated mean
      difference (MD) between groups. Skewed data have been presented in the Data and
      analyses as 'other data', with acknowledged means and standard deviations. We
      assessed risk of bias for the included study and used GRADE to create a 'Summary
      of findings' table. MAIN RESULTS: We included only one study that compared
      nidotherapy-enhanced standard care with standard care alone (total 52
      participants); this study was classified by its authors as a 'pilot study'. The
      duration of the included study was 18 months in total. The single study examined
      the short-term (up to six months) and medium-term (between six and 12 months)
      effects of nidotherapy-enhanced standard care versus standard care.Nidotherapy
      enhanced standard care was favoured over standard care for social functioning in
      both the short term (n = 50, 1 RCT, MD -2.10, 95% CI -4.66 to 0.46) and medium
      term (n = 37, 1 RCT, MD -1.70, 95% CI -4.60 to 1.20, Very low quality); however,
      these results did not reach statistical significance. Results concerning
      engagement with non-inpatient services favoured the intervention group in both
      the short term (n = 50, 1 RCT, MD 2.00, 95% CI 0.13 to 3.87) and medium term (n =
      37, 1 RCT, MD 1.70, 95% CI -0.09 to 3.49), with statistical significance evident
      in the short term, but not in the medium term. Results of people leaving the
      study early favoured the intervention in the short term (n = 52, 1 RCT, RR 0.86,
      95% CI 0.06 to 12.98), with slight favour of the control group at medium term (n
      = 50, 1 RCT, RR 0.99, 95% CI 0.39 to 2.54); again, these results did not reach
      statistical significance. Results for the adverse effects/events of death
      (measured by 12 months) favoured the intervention (n = 52, 1 RCT, RR 0.29, 95% CI
      0.01 to 6.74, Very low quality) but with no statistical significance. Skewed
      results were available for mental state, service use, and economic outcomes, and
      present a mixed picture of the benefits of nidotherapy. AUTHORS' CONCLUSIONS:
      Further research is needed into the possible benefits or harms of this newly
      formulated therapy. Until such research is available, patients, clinicians,
      managers and policymakers should consider it an experimental approach.

PMID- 23543582
TI  - Methods of term labour induction for women with a previous caesarean section.
AB  - BACKGROUND: Induction of labour is a common obstetric intervention, with between
      20% and 30% of births reported to occur following induction of labour. Women with
      a prior caesarean delivery have an increased risk of uterine rupture,
      particularly when labour is induced. For women who have had a previous caesarean
      birth and who require induction of labour in a subsequent pregnancy, it is
      unclear which method of cervical ripening and labour induction is preferable.
      OBJECTIVES: To assess the benefits and harms associated with different methods
      used to induce labour in women who have had a previous caesarean birth and
      require induction of labour in a subsequent pregnancy. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July
      2012) and reference lists of retrieved studies. SELECTION CRITERIA: All
      randomised controlled trials comparing any method of third trimester cervical
      ripening or labour induction, with placebo/no treatment or other methods in women
      with prior caesarean section requiring labour induction in a subsequent pregnancy
      were included.Methods of cervical ripening or labour induction could include:
      prostaglandin medication (including oral or vaginal prostaglandin E2 (PGE2) and
      misoprostol); mifepristone; mechanical methods (including Foley catheters and
      double balloon catheters); oxytocin, or placebo. DATA COLLECTION AND ANALYSIS:
      The two review authors independently assessed studies for inclusion and trial
      quality. Any disagreement was resolved by discussion. Both review authors
      independently extracted data and data were checked for accuracy. MAIN RESULTS:
      Two studies (involving a total of 80 women) were included. However, the two
      included studies used different methods and thus, meta-analysis was not
      appropriate. The two included studies compared 2.5 mg vaginal PGE2 inserts versus
      oxytocin (Taylor and colleagues) and misoprostol versus oxytocin (Wing and
      colleagues). Risk of bias in the included studies was judged 'low' and 'unclear'
      respectively.Vaginal PGE2 inserts versus oxytocin - Taylor and colleagues
      included 42 women, equally distributed over both groups. Baseline
      characteristics, and reasons for labour induction were comparable between the
      groups. There were no significant differences in any of the outcome measures
      reported (caesarean section, instrumental vaginal deliveries, epidural analgesia,
      Apgar score, perinatal death). One uterine rupture occurred in the prostaglandin
      group, after the use of prostaglandins and oxytocin, while no ruptures occurred
      in the oxytocin group (one study, 42 women; risk ratio (RR) 3.00, 95% confidence
      interval (CI) 0.13 to 69.70).Misoprostol versus oxytocin - the study conducted by
      Wing and colleagues was stopped prematurely due to safety concerns after the
      inclusion of 38 women. Seventeen women had been included in the misoprostol
      group, and 21 women in the oxytocin group. There were no significant difference
      in the only outcome measure reported by the authors, uterine rupture, which
      occurred twice in the misoprostol group, and did not occur in the oxytocin group
      (one study; 38 women; RR 6.11, 95% CI 0.31 to 119.33). AUTHORS' CONCLUSIONS:
      There is insufficient information available from randomised controlled trials on
      which to base clinical decisions regarding the optimal method of induction of
      labour in women with a prior caesarean birth.

PMID- 23543584
TI  - FSH replaced by low-dose hCG in the late follicular phase versus continued FSH
      for assisted reproductive techniques.
AB  - BACKGROUND: During controlled ovarian hyperstimulation (COH) follicle-stimulating
      hormone (FSH) is frequently used for several days to achieve follicular
      development. FSH is a relatively expensive drug, substantially contributing to
      the total expenses of assisted reproductive techniques (ART). When follicles
      achieve a diameter greater than 10 mm they start expressing luteinising hormone
      (LH) receptors. At this point, FSH might be replaced by low-dose human chorionic
      gonadotropin (hCG), which is less expensive. In addition to cost reduction,
      replacing FSH by low-dose hCG has a theoretical potential to reduce the incidence
      of ovarian hyperstimulation syndrome (OHSS). OBJECTIVES: To evaluate the
      effectiveness and safety of using low-dose hCG to replace FSH during the late
      follicular phase in women undergoing COH for assisted reproduction, compared to
      the use of a conventional COH protocol. SEARCH METHODS: We searched for
      randomised controlled trials (RCT) in electronic databases (Menstrual Disorders
      and Subfertility Group Specialized Register, CENTRAL, MEDLINE, EMBASE, PsycINFO,
      CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials,
      World Health Organization International Clinical Trials Registry Platform),
      conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey);
      additionally we handsearched the reference list of included studies and similar
      reviews. The last electronic search was performed in February 2013.. SELECTION
      CRITERIA: Only true RCTs comparing the replacement of FSH by low-dose hCG during
      late follicular phase of COH were considered eligible; quasi or pseudo-randomised
      trials were not included. Cross-over trials would be included only if data
      regarding the first treatment of each participant were available; trials that
      included the same participant more than once would be included only if each
      participant was always allocated to the same intervention and follow-up periods
      were the same in both/all arms, or if data regarding the first treatment of each
      participant were available. We excluded trials that sustained FSH after starting
      low-dose hCG and those that started FSH and low-dose hCG at the same time. DATA
      COLLECTION AND ANALYSIS: Study eligibility, data extraction, and assessment of
      the risk of bias were performed independently by two review authors, and
      disagreements were solved by consulting a third review author. We corresponded
      with study investigators in order to solve any query, as required. The overall
      quality of the evidence was assessed in a GRADE summary of findings table. MAIN
      RESULTS: The search retrieved 1585 records; from those five studies were
      eligible, including 351 women (intervention = 166; control = 185). All studies
      were judged to be at high risk of bias. All reported per-woman rather than per
      cycle data.When use of low-dose hCG to replace FSH was compared with conventional
      COH for the outcome of live birth, confidence intervals were very wide and
      findings were compatible with appreciable benefit, no effect or appreciable harm
      for the intervention (RR 1.56, 95% CI 0.75 to 3.25, 2 studies, 130 women, I2 =
      0%, very-low-quality evidence). This suggests that for women with a 14% chance of
      achieving live birth using conventional COH, the chance of achieving live birth
      using low-dose hCG would be between 10% and 45%.Similarly confidence intervals
      were very wide for the outcome of OHSS and findings were compatible with benefit,
      no effect or harm for the intervention (OR 0.30, 95% CI 0.06 to 1.59, 5 studies,
      351 women, I2 = 59%, very-low-quality evidence). This suggests that for women
      with a 3% risk of OHSS using conventional COH, the risk using low-dose hCG would
      be between 0% and 4%.The confidence intervals were wide for the outcome of
      ongoing pregnancy and findings were compatible with benefit or no effect for the
      intervention (RR 1.14, 95% CI 0.81 to 1.60, 3 studies, 252 women, I2 = 0%, low
      quality evidence). This suggests that for women with a 32% chance of achieving
      ongoing pregnancy using conventional COH, the chance using low-dose hCG would be
      between 27% and 53%.The confidence intervals were wide for the outcome of
      clinical pregnancy and findings were compatible with benefit or no effect for the
      intervention (RR 1.19, 95% CI 0.92 to 1.55, 5 studies, 351 women, I2 = 0%, low
      quality evidence). This suggests that for women with a 35% chance of achieving
      clinical pregnancy using conventional COH, the chance using low-dose hCG would be
      between 32% and 54%.The confidence intervals were very wide for the outcome of
      miscarriage and findings were compatible with benefit, no effect or harm for the
      intervention (RR 1.08, 95% CI 0.50 to 2.31, 3 studies, 127 pregnant women, I2 =
      0%, very-low-quality evidence). This suggests that for pregnant women with a 16%
      risk of miscarriage using conventional COH, the risk using low-dose hCG would be
      between 8% and 36%.The findings for the outcome of FSH consumption were
      compatible with benefit for the intervention (MD -639 IU, 95% CI -893 to -385, 5
      studies, 333 women, I2 = 88%, moderate-quality evidence).The findings for the
      outcome of number of oocytes retrieved were compatible with no effect for the
      intervention (MD -0.12 oocytes, 95% CI -1.0 to 0.8 oocytes, 5 studies, 351 women,
      I2 = 0%, moderate-quality evidence). AUTHORS' CONCLUSIONS: We are very uncertain
      of the effect on live birth, OHSS and miscarriage of using low-dose hCG to
      replace FSH during the late follicular phase of COH in women undergoing ART,
      compared to the use of conventional COH. The current evidence suggests that this
      intervention does not reduce the chance of ongoing and clinical pregnancy; and
      that it is likely to result in an equivalent number of oocytes retrieved
      expending less FSH. More studies are needed to strengthen the evidence regarding
      the effect of this intervention on important reproductive outcomes.

PMID- 23543585
TI  - Single dose oral ibuprofen plus codeine for acute postoperative pain in adults.
AB  - BACKGROUND: There is good evidence that combining two different analgesics in
      fixed doses in a single tablet can provide better pain relief in acute pain and
      headache than either drug alone, and that the drug-specific effects are
      essentially additive. This appears to be broadly true in postoperative pain and
      migraine headache across a range of different drug combinations and when tested
      in the same and different trials. Some combinations of ibuprofen and codeine are
      available without prescription (but usually only from a pharmacy) where the dose
      of codeine is lower, and with a prescription when the dose of codeine is higher.
      OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral
      dose of ibuprofen plus codeine for moderate to severe postoperative pain. We
      compared ibuprofen plus codeine with placebo and with the same dose of ibuprofen
      alone. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, ClinicalTrials.gov,
      and reference lists of articles. The date of the most recent search was 30
      September 2012. SELECTION CRITERIA: Randomised, double-blind, placebo- or active
      controlled clinical trials of single dose oral ibuprofen plus codeine for acute
      postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors
      independently considered trials for inclusion in the review, assessed quality,
      and extracted data. We used the area under the pain relief versus time curve to
      derive the proportion of participants prescribed ibuprofen plus codeine, placebo,
      or the same dose of ibuprofen alone with at least 50% pain relief over six hours,
      using validated equations. We calculated the relative risk (RR) and number needed
      to treat to benefit (NNT). We used information on the use of rescue medication to
      calculate the proportion of participants requiring rescue medication and the
      weighted mean of the median time to use. We also collected information on adverse
      effects. Analyses were planned for different doses of ibuprofen and codeine, but
      especially for codeine where we set criteria for low (< 10 mg), medium (10 to 20
      mg), and high (> 20 mg) doses. MAIN RESULTS: Information was available from six
      studies with 1342 participants, with a variety of doses of ibuprofen and codeine.
      In four studies (443 participants) using ibuprofen 400 mg plus codeine 25.6 to 60
      mg (high dose codeine) 64% of participants had at least 50% maximum pain relief
      with the combination compared to 18% with placebo. The NNT was 2.2 (95% CI 1.8 to
      2.6). In three studies (204 participants) ibuprofen plus codeine (any dose) was
      better than the same dose of ibuprofen (69% versus 55%) but the result was barely
      significant with a relative benefit of 1.3 (95% CI 1.01 to 1.6). In two studies
      (159 participants) ibuprofen plus codeine appeared to be better than the same
      dose of codeine alone (69% versus 33%), but no analysis was done. There was no
      difference between the combination and placebo in the reporting of adverse events
      in these acute studies. AUTHORS' CONCLUSIONS: The combination of ibuprofen 400 mg
      plus codeine 25.6 to 60 mg demonstrates good analgesic efficacy. Very limited
      data suggest that the combination is better than the same dose of either drug
      alone. Use of combination analgesics that contain codeine has been a source of
      some concern because of misuse from over-the-counter preparations.

PMID- 23543586
TI  - Preventing falls in older people: the story of a Cochrane review.

PMID- 23543587
TI  - Frequency of TP53 Mutations and its Impact on Drug Sensitivity in Acute Myeloid
      Leukemia?
AB  - The purpose of this study is to find out the frequency of TP53 mutations in acute
      myeloid leukemia (AML) patients and correlate sensitivity of drug response with
      TP53 mutations. In AML more than 90 % of cases comprise of wild type TP53. 94.2 %
      of TP53 mutations are found within exon 5-8 of which 73 % are point mutations.
      TP53 mutations were analysed with high resolution melting curve analysis. We
      analysed 106 AML samples of which we found nine mutations which represents 8.5 %
      mutation rate and found one rare SNP. The effect of TP53 mutations were studied
      on the chemosensitivity of two new drugs AZD115 and RHPS4, an Aurora Kinase B
      inhibitor and Telomerase inhibitor respectively. Four mutations were found out of
      17 for RHPS4 stating significant (p = 0.002) increase in sensitivity and no
      mutation found in AZD1152 database, but need more study to get definite
      conclusion.

PMID- 23543588
TI  - Neutrophilic eccrine hidradenitis: a new culprit-carbamazepine.
AB  - Neutrophilic eccrine hidradenitis (NEH) is a distinctive dermatosis occurring in
      patients with malignancy or undergoing chemotherapy. This disorder is
      characterized by a neutrophilic infiltrate around the eccrine glands and
      secretory coils, and is associated with necrosis. It must be distinguished from
      infections, drug eruptions, malignancies or other forms of skin diseases. As it
      is a self-limiting condition, establishing the diagnosis will avoid unnecessary
      investigations and treatment. Here we report a case of NEH in a 40-year-old woman
      suspected to be due to carbamazepine.

PMID- 23543589
TI  - Cohort Profile: The Likoma Network Study (LNS).
AB  - The Likoma network study (LNS) investigates the sexual networks connecting the
      inhabitants of Likoma, a small island of Lake Malawi with high HIV prevalence.
      Whereas previous studies of sexual networks and HIV/AIDS in sub-Saharan countries
      have focused solely on the personal networks of a small number of respondents,
      the LNS attempts to document the sexual networks of the entire adult population
      of Likoma. To do so, it uses a unique sociocentric study design, in which all
      members of the local population are contacted for a survey interview and are
      asked to nominate their five most recent sexual partners. Using these data, quasi
      complete 'maps' of the sexual networks connecting inhabitants of the island can
      be constructed. These maps allow investigation of the impact of networks on HIV
      epidemiology and can inform mathematical models of HIV prevention. In addition to
      data on sexual networks, the LNS data include information on the social networks
      (e.g. friendship), socioeconomic characteristics and HIV status of Likoma's
      residents. Baseline data were collected in 2005-06. A first follow-up was
      conducted in 2007-08 and a second follow-up is planned for early 2013. Access to
      the LNS data is contingent upon review of a short concept paper and forming
      collaborations with LNS investigators. 

PMID- 23543591
TI  - Donation from old living donors: how safe is it?
AB  - As the rate of living kidney donor (LKD) transplantations increases, the
      selection of extended criteria donors such as old donors (>60-65 years) becomes
      more common. The pool of these old donors is probably wider than we think,
      especially if we tolerate a lower glomerular filtration rate (GFR) than the gold
      standard of 80 mL/min/1.73 m(2). Several important studies with large cohorts of
      living donors including old subjects have been published these last few years and
      give insights on the outcome in this subpopulation. The risk of death and end
      stage renal disease (ESRD) is similar to that of matched controls from the
      general population. Post-donation GFR, as a result of glomerulopaenia, is lower
      in old than in younger donors but pre-donation as well as the rate of function
      loss is not different between young and old donors. Nearly 80% of donors over 60
      have <60 mL/min GFR post-donation, the risk of cardiovascular mortality and
      progression to ESRD in the long term, as in the general population, is under
      question. Despite reduced renal function of the old kidney, the results of
      transplantation from an old living donor appeared to be equivalent to deceased
      transplantation from a younger donor. Finally, transplantation from an old living
      donor appeared to be a reasonably safe procedure for both the donor and the
      recipient and the age per se is certainly not a contraindication to donation. 

PMID- 23543590
TI  - Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.
AB  - BACKGROUND: Recent experimental work suggests a paradox: although uremia evokes
      systemic toxicities, in the setting of AKI, it can induce intrarenal
      cytoprotective and anti-inflammatory effects. Whether these influences can
      attenuate post-ischemic kidney disease progression remains unknown. METHODS: To
      explore this possibility, male CD-1 mice were subjected to a 30-min unilateral
      (left) kidney ischemia model, previously shown to reduce renal mass by ~50% over
      2-3 weeks. Stepwise azotemia/acute uremia was superimposed by inducing different
      lengths of contralateral (right) kidney ischemia (0, 15, 18, 20 min). Subsequent
      loss of left renal mass (kidney weight) was assessed 2 weeks later and contrasted
      with the degree of initial azotemia 24-h BUN. RESULTS: A striking correlation
      between 24-h BUNs and 2-week left renal mass was observed (r, 0.77; P < 0.001).
      With 20 min of right kidney ischemia, left kidney size was completely preserved.
      This preservation did not result from increased tubular cell proliferation or
      decreased microvascular loss, as gauged by KI-67 and CD-34 immunohistochemistry,
      respectively. Rather, an early reduction in proximal tubule cell dropout (as
      judged by renal cortical N-acetyl-glucosaminidase content), with a subsequent
      preservation of tubule mass, was observed. CONCLUSIONS: In summary, these
      findings advance a novel concept: acute uremia can confer early post-ischemic
      cytoprotection resulting in a slowed progression of post-ischemic kidney disease.

PMID- 23543592
TI  - Global differences in dialysis modality mix: the role of patient characteristics,
      macroeconomics and renal service indicators.
AB  - BACKGROUND: An increase in the dialysis programme expenditure is expected in most
      countries given the continued rise in the number of people with end-stage renal
      disease (ESRD) globally. Since chronic peritoneal dialysis (PD) therapy is
      relatively less expensive compared with haemodialysis (HD) and because there is
      no survival difference between PD and HD, identifying factors associated with PD
      use is important. METHODS: Incidence counts for the years 2003-05 were available
      from 36 countries worldwide. We studied associations of population
      characteristics, macroeconomic factors and renal service indicators with the
      percentage of patients on PD at Day 91 after starting dialysis. With linear
      regression models, we obtained relative risks (RRs) with 95% confidence intervals
      (CIs). RESULTS: The median percentage of incident patients on PD was 12%
      (interquartile range: 7-26%). Determinants independently associated with lower
      percentages of patients on PD were as follows: patients with diabetic kidney
      disease (per 5% increase) (RR 0.93; 95% CI 0.89-0.97), health expenditure as %
      gross domestic product (per 1% increase) (RR 0.93; 95% CI 0.87-0.98), private-for
      profit share of HD facilities (per 1% increase) (RR 0.996; 95% CI 0.99-1.00; P =
      0.04), costs of PD consumables relative to staffing (per 0.1 increase) (RR 0.97;
      95% CI 0.95-0.99). CONCLUSIONS: The factors associated with a lower percentage of
      patients on PD include higher diabetes prevalence, higher healthcare
      expenditures, larger share of private-for-profit centres and higher costs of PD
      consumables relative to staffing. Whether dialysis modality mix can be influenced
      by changing healthcare organization and funding requires additional studies.

PMID- 23543595
TI  - Arteriovenous access failure: more than just intimal hyperplasia?
AB  - Haemodialysis vascular access patency is severely compromised by fistula non
      maturation and access stenosis. Intimal hyperplasia (IH) is considered the
      culprit lesion in failed fistulas, resulting in luminal narrowing and stenosis.
      This review focuses on the biology and pathophysiology of fistula failure and
      highlights not only the classically associated IH but also some relatively
      neglected but potentially important contributors such as inadequate outward
      remodelling. In addition, the complex process and fragile balance of successful
      fistula maturation might be partially hindered by pre-existent chronic kidney
      disease-mediated vasculopathy. Further unravelling the (patho)physiology of
      outward remodelling and IH could contribute to novel therapies and enhance
      fistula patency.

PMID- 23543593
TI  - Inhibition of Comt with tolcapone slows progression of polycystic kidney disease
      in the more severely affected PKD/Mhm (cy/+) substrain of the Hannover Sprague
      Dawley rat.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the
      most common human inherited diseases. Modifier genes seem to modulate the disease
      progression and might therefore be promising drug targets. Although a number of
      modifier loci have been already identified, no modifier gene has been proven to
      be a real modifier yet. METHODS: Gene expression profiling of two substrains of
      the Han:SPRD rat, namely PKD/Mhm and PKD/US, both harboring the same mutation,
      was conducted in 36-day-old animals. Catechol-O-methyltransferase (Comt) was
      identified as a potential modifier gene. A 3-month treatment with tolcapone, a
      selective inhibitor of Comt, was carried out in PKD/Mhm and PKD/US (cy/+)
      animals. RESULTS: Comt is localized within a known modifier locus of PKD (MOP2).
      The enzyme encoding gene was found upregulated in the more severely affected
      PKD/Mhm substrain and was hence presumed to be a putative modifier gene of PKD.
      The treatment with tolcapone markedly attenuated the loss of renal function,
      inhibited renal enlargement, shifted the size distribution of renal cysts and
      retarded cell proliferation, apoptosis, inflammation and fibrosis development in
      affected (cy/+) male and female PKD/Mhm and PKD/US rats. CONCLUSIONS: Comt has
      been confirmed to be the first reported modifier gene for PKD and tolcapone
      offers a promising drug for treating PKD.

PMID- 23543594
TI  - Uric acid and chronic kidney disease: which is chasing which?
AB  - Serum uric acid is commonly elevated in subjects with chronic kidney disease
      (CKD), but was historically viewed as an issue of limited interest. Recently,
      uric acid has been resurrected as a potential contributory risk factor in the
      development and progression of CKD. Most studies documented that an elevated
      serum uric acid level independently predicts the development of CKD. Raising the
      uric acid level in rats can induce glomerular hypertension and renal disease as
      noted by the development of arteriolosclerosis, glomerular injury and
      tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid
      concentrations may slow the progression of renal disease in subjects with CKD.
      While further clinical trials are necessary, uric acid is emerging as a
      potentially modifiable risk factor for CKD. Gout was considered a cause of CKD in
      the mid-nineteenth century, and, prior to the availability of therapies to lower
      the uric acid level, the development of end-stage renal disease was common in
      gouty patients. In their large series of gouty subjects Talbott and Terplan found
      that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis,
      glomerulosclerosis and interstitial fibrosis). Additional studies showed that
      during life impaired renal function occurred in half of these subjects. As many
      of these subjects had urate crystals in their tubules and interstitium,
      especially in the outer renal medulla, the disease became known as gouty
      nephropathy. The identity of this condition fell in question as the presence of
      these crystals may occur in subjects without renal disease; furthermore, the
      focal location of the crystals could not explain the diffuse renal scarring
      present. In addition, many subjects with gout also had coexistent conditions such
      as hypertension and vascular disease, leading some experts to suggest that the
      renal injury in gout was secondary to these latter conditions rather than to uric
      acid per se. Indeed, gout was removed from the textbooks as a cause of CKD, and
      the common association of hyperuricemia with CKD was solely attributed to the
      retention of serum uric acid that is known to occur as the glomerular filtration
      rate falls. Renewed interest in uric acid as a cause of CKD occurred when it was
      realized that invalid assumptions had been made in the arguments to dismiss uric
      acid as a risk factor for CKD. The greatest assumption was that the mechanism by
      which uric acid would cause kidney disease would be via the precipitation as
      crystals in the kidney, similar to the way it causes gout. However, when
      laboratory animals with CKD were made hyperuricemic, the renal disease progressed
      rapidly despite an absence of crystals in the kidney. Since this seminal study,
      there has been a renewed interest in the potential role uric acid may have in
      both acute and CKD. We briefly review some of the major advances that have
      occurred in this field in the last 15 years.

PMID- 23543596
TI  - Association analysis of HSP70A1A haplotypes with heat tolerance in Chinese
      Holstein cattle.
AB  - Single-nucleotide polymorphisms (SNPs) in the coding and untranslated regions of
      heat shock 70 kDa protein 1A (HSP70A1A), an inducible molecular chaperone that is
      responsible for cellular protection against heat stress, have been reported as
      being associated with heat tolerance. A fragment of the HSP70A1A gene was
      amplified in Chinese Holstein cattle and eight novel mutations were found. We
      performed comprehensive linkage disequilibrium (LD) and haplotype analyses of the
      eight SNPs of the HSP70A1A gene and examined their involvement in heat resistance
      in 600 Chinese Holstein cattle. Our results revealed the presence of significant
      differences between individuals carrying haplotype 1 and those without haplotype
      1 for most of the heat-tolerance traits. Haplotype 1 increased the risk of heat
      stress; however, association analysis of its combination with haplotype 2 showed
      the lowest rectal temperature and red blood cell K(+) level, moderate respiratory
      rate, and the highest red blood cell NKA level, suggesting a heterozygote
      advantage in the penetration of the phenotype. Protein expression levels in white
      blood cells among haplotype combinations further confirmed the hypothesis that
      heterozygotes for haplotypes 1 and 2 are more sensitive to heat stress. We
      presume that these mutations may be useful in the future as molecular genetic
      markers to assist selection for heat tolerance in cattle. 

PMID- 23543597
TI  - Patient-derived stem cells: pathways to drug discovery for brain diseases.
AB  - The concept of drug discovery through stem cell biology is based on technological
      developments whose genesis is now coincident. The first is automated cell
      microscopy with concurrent advances in image acquisition and analysis, known as
      high content screening (HCS). The second is patient-derived stem cells for
      modeling the cell biology of brain diseases. HCS has developed from the
      requirements of the pharmaceutical industry for high throughput assays to screen
      thousands of chemical compounds in the search for new drugs. HCS combines new
      fluorescent probes with automated microscopy and computational power to quantify
      the effects of compounds on cell functions. Stem cell biology has advanced
      greatly since the discovery of genetic reprograming of somatic cells into induced
      pluripotent stem cells (iPSCs). There is now a rush of papers describing their
      generation from patients with various diseases of the nervous system. Although
      the majority of these have been genetic diseases, iPSCs have been generated from
      patients with complex diseases (schizophrenia and sporadic Parkinson's disease).
      Some genetic diseases are also modeled in embryonic stem cells (ESCs) generated
      from blastocysts rejected during in vitro fertilization. Neural stem cells have
      been isolated from post-mortem brain of Alzheimer's patients and neural stem
      cells generated from biopsies of the olfactory organ of patients is another
      approach. These "olfactory neurosphere-derived" cells demonstrate robust disease
      specific phenotypes in patients with schizophrenia and Parkinson's disease. HCS
      is already in use to find small molecules for the generation and differentiation
      of ESCs and iPSCs. The challenges for using stem cells for drug discovery are to
      develop robust stem cell culture methods that meet the rigorous requirements for
      repeatable, consistent quantities of defined cell types at the industrial scale
      necessary for HCS.

PMID- 23543599
TI  - Cohort profile: The Gubbio Population Study.
AB  - The Gubbio Study is a prospective epidemiological study on the population
      residing in the city of Gubbio, Italy. Original objectives of the study were the
      control of hypertension and the role of cellular electrolyte handling in
      hypertension. Other objectives were added during the 30-year activity of the
      study. The original target cohort consists of individuals aged >=5 years residing
      within the medieval walls of the city. To complete family genealogies,
      individuals residing outside the city were also included. Three active screenings
      (exams) were conducted. A total of 5376 individuals (response rate 92%)
      participated in Exam 1 which was performed in 1983-86. Follow-up exams were
      completed between 1989-92 and 2001-2007. Data categories included demographics,
      personal and family medical history, lifestyle habits, education, type of work,
      anthropometry, blood pressure, pulse rate, blood biochemistry, urine biochemistry
      and special investigations on cellular electrolyte handling. Electrocardiogram,
      echocardiogram, 24-h ambulatory blood pressure and uroflowmetry were performed in
      selected subgroups defined by age and/or sex. Data about hospitalizations,
      mortality and causes of death were collected starting from completion of Exam 1.
      The study shared the data with other studies.

PMID- 23543600
TI  - Second-hand smoke in mental healthcare settings: time to implement total smoke
      free bans?
AB  - BACKGROUND: Second-hand smoke is associated with adverse health effects. Many
      countries have extended smoke-free policies to public buildings and workplaces
      such as hospitals, but mental health units have usually been exempted from
      complete smoke-free bans. The objective of this study was to evaluate second-hand
      smoke levels in mental health units with different types of smoking bans. Method
      We conducted a cross-sectional study to evaluate second-hand smoke in 64 mental
      health inpatient units (95.5% of the all such units) in Catalonia, Spain. We
      measured air concentrations of particulate matter <2.5 MUm (PM2.5) as a marker of
      second-hand smoke in different locations at each unit. RESULTS: The geometric
      mean (95% confidence interval) of the PM2.5 concentration was 8.81 MUg/m(3) (8.06
      9.56) in units with indoor and outdoor smoking bans, 13.80 MUg/m(3) (13.23-14.36)
      in units with indoor smoking bans that allowed smoking in outdoor areas, 24.29
      MUg/m(3) (23.50-25.03) in units with indoor smoking rooms and 51.00 MUg/m(3)
      (49.83-52.04) in units that allowed smoking in common indoor areas (P < 0.05).
      The regression model adjusted for confounding variables showed a linear increase
      of PM2.5. The PM2.5 concentration in smoking rooms was 286.50 MUg/m(3) (283.95
      288.89). CONCLUSIONS: Only units with indoor and outdoor smoking bans had PM2.5
      levels below the standard recommended WHO levels of 10 MUg/m(3). Units with more
      permissive smoking policies had PM2.5 levels from second-hand smoke that have
      harmful health effects.

PMID- 23543601
TI  - Theoretical considerations and practical approaches to address the effect of anti
      drug antibody (ADA) on quantification of biotherapeutics in circulation.
AB  - Continuous improvement in bioanalytical method development is desired in order to
      ensure the quality of the data and to better support pharmacokinetic (PK) and
      safety studies of biotherapeutics. One area that has been getting increasing
      attention recently is in the assessment of "free" and "total" analyte and the
      impact of the assay format on those assessments. To compliment these
      considerations, the authors provide a critical review of available literature and
      prospectively explore methods to mitigate the potential impact of anti-drug
      antibody on PK assay measurement. This challenge is of particular interest and
      importance since biotherapeutic drugs often elicit an immune response, and thus
      may have a direct impact on quantification of the drug for its PK and safety
      evaluations. 

PMID- 23543603
TI  - Sequential bioequivalence trial designs with increased power and controlled type
      I error rates.
AB  - Methods to implement two-stage designs in two-treatment, two-sequence, and two
      period crossover bioequivalence studies have only recently been developed. The
      two-stage methods have so far only been described for a targeted study power of
      80%. Since it is sometimes desirable to increase the targeted power to 90%, this
      study identifies sets of alphas that work for the recently developed two-stage
      methods while controlling type I error rates around 5% for assumed geometric mean
      test/reference ratios of 0.90 and 0.95 at targeted power of 90%, and provides a
      characterization of the methods in terms of the resulting sample sizes and power.
      Depending on the actual variability and the chosen sample size at stage 1, the
      actual power will be between 83% and 100%. The previously characterised methods
      at target power 80% as well as 90% result in trivial inflation of type 1 error,
      but the type 1 error inflation at 90% target powers with decreased alpha at the
      second stage result in slightly less inflation. These results may be useful for
      applicant wishing to achieve increased power in bioequivalence trials without a
      penalty for type I error rates. 

PMID- 23543602
TI  - Drug-drug interaction studies: regulatory guidance and an industry perspective.
AB  - Recently, the US Food and Drug Administration and European Medicines Agency have
      issued new guidance for industry on drug interaction studies, which outline
      comprehensive recommendations on a broad range of in vitro and in vivo studies to
      evaluate drug-drug interaction (DDI) potential. This paper aims to provide an
      overview of these new recommendations and an in-depth scientifically based
      perspective on issues surrounding some of the recommended approaches in emerging
      areas, particularly, transporters and complex DDIs. We present a number of
      theoretical considerations and several case examples to demonstrate complexities
      in applying (1) the proposed transporter decision trees and associated criteria
      for studying a broad spectrum of transporters to derive actionable information
      and (2) the recommended model-based approaches at an early stage of drug
      development to prospectively predict DDIs involving time-dependent inhibition and
      mixed inhibition/induction of drug metabolizing enzymes. We hope to convey the
      need for conducting DDI studies on a case-by-case basis using a holistic
      scientifically based interrogative approach and to communicate the need for
      additional research to fill in knowledge gaps in these areas where the science is
      rapidly evolving to better ensure the safety and efficacy of new therapeutic
      agents. 

PMID- 23543604
TI  - A case of CMV endotheliitis treated with intravitreal ganciclovir injection.
AB  - We report a case of CMV corneal endotheliitis that was treated with intravitreal
      ganciclovir injection. A 56-year-old man who has suffered from uveitis was
      referred to our clinic due to corneal endothelial abnormality. Slit lamp
      examination showed a localized sectoral corneal edema and linear keratic
      precipitates along the boundary of edema. In spite of treatment with oral steroid
      and acyclovir, the disease progressed and two new coin-like lesions were
      developed. After topical ganciclovir and intavitreal injection of ganciclovir,
      the corneal lesions disappeared.

PMID- 23543605
TI  - l-Carvyl esters as penetration enhancers for the transdermal delivery of 5
      fluorouracil.
AB  - To develop effective and safe penetration enhancers, a series of l-carvyl esters,
      namely, 5-isopropenyl-2-methylcyclohex-2-en-1-yl heptanoate (C-HEP), 5
      isopropenyl-2- methylcyclohex-2-en-1-yl octanoate (C-OCT), 5-isopropenyl-2
      methylcyclohex-2-en-1-yl decanoate (C-DEC), 5-isopropenyl-2-methylcyclohex-2-en-1
      yl dodecanoate (C-DOD), 5-isopropenyl-2-methylcyclohex-2-en-1-yl tetradecanoate
      (C-TET), and 5-isopropenyl-2-methylcyclohex-2-en-1-yl palmitate (C-PAL), was
      synthesized from l-carveol and saturated fatty acids (C7-C16). The volatility of
      l-carveol and l-carvyl esters was evaluated by a live weight loss experiment. The
      enhancing effects of l-carvyl esters on 5-fluorouracil (FU) were investigated in
      the in vitro permeation experiment on rat skin. The stratum corneum (SC) uptakes
      of the enhancers were tested in vitro by gas chromatography. Only the l-carvyl
      esters with a moderate SC uptake, namely, C-OCT (C8), C-DEC (C10), and C-DOD
      (C12), showed a potential to enhance FU skin permeation. An evident parabolic
      relationship was found between the permeation enhancement of FU and the SC uptake
      of the l-carvyl esters. The l-carvyl esters with a chain length of C8-C12 seemed
      to be favorable for FU.

PMID- 23543607
TI  - Influence of microcrystal formulation on in vivo absorption of celecoxib in rats.
AB  - The objective of this study was to prepare celecoxib microcrystals using
      different stabilizers in order to evaluate the influence of microcrystal
      formulation on the in vitro dissolution rate and in vivo absorption after oral
      administration of celecoxib in rats. Three celecoxib microcrystals (MC1, MC2, and
      MC3) were prepared using solvent change method. Microcrystals were evaluated for
      morphology, particle size, crystallinity, solubility, in vitro dissolution, and
      in vivo absorption in rats. Scanning electron microscopy images showed distinct
      differences in the morphologies and dimensions of various celecoxib
      microcrystals. The particle size of all microcrystals was significantly (P<0.05)
      reduced relative to plain celecoxib. The DSC and XRD results revealed that MC1
      retain drug crystallinity relative to control crystals, MC2, and MC3. All
      microcrystals showed marked increase in the drug dissolution parameters
      particularly MC1 that exhibited a prompt drug release and significantly (P<0.05)
      higher values of % dissolution efficiency as compared to control celecoxib and
      the other microcrystals. The influence of microcrystals on the in vivo absorption
      of celecoxib was studied in rats in comparison to plain drug. The results of in
      vivo absorption study in rats indicated that MC1 significantly improved the rate
      and extent of celecoxib absorption than plain celecoxib. The mean relative
      bioavailability of MC1 formulation to plain celecoxib was 157.55+/-20.18%. In
      conclusion, microcrystal formulation of celecoxib results not only in an
      enhancement of dissolution parameters but also improves the bioavailability of
      celecoxib in rats.

PMID- 23543608
TI  - Presence and dissemination of the multiresistance gene cfr in Gram-positive and
      Gram-negative bacteria.
AB  - The emergence of the multiresistance gene cfr in staphylococci is of global
      concern. In addition to conferring resistance to phenicols, lincosamides,
      pleuromutilins, streptogramin A antibiotics and selected 16-membered macrolides,
      the cfr gene also confers resistance to the oxazolidinone linezolid. Linezolid is
      a last-resort antimicrobial agent for the treatment of serious infections in
      humans caused by resistant Gram-positive bacteria. The cfr gene is often located
      on plasmids and several cfr-carrying plasmids have been described, which differ
      in their structure, their size and the presence of additional resistance genes.
      These plasmids are important vehicles that promote the spread of the cfr gene not
      only among bacteria of the same species, but also among those of different
      species and genera. Moreover, the cfr gene has been identified in close proximity
      to different insertion sequences, which most probably also play an important role
      in its dissemination. This review summarizes current knowledge on the genetic
      environment of the multiresistance gene cfr with particular reference to mobile
      genetic elements and co-located resistance genes that may support its emergence. 

PMID- 23543606
TI  - A review of polymeric refabrication techniques to modify polymer properties for
      biomedical and drug delivery applications.
AB  - Polymers are extensively used in the pharmaceutical and medical field because of
      their unique and phenomenal properties that they display. They are capable of
      demonstrating drug delivery properties that are smart and novel, such properties
      that are not achievable by employing the conventional excipients. Appropriately,
      polymeric refabrication remains at the forefront of process technology
      development in an endeavor to produce more useful pharmaceutical and medical
      products because of the multitudes of smart properties that can be attained
      through the alteration of polymers. Small alterations to a polymer by either
      addition, subtraction, self-reaction, or cross reaction with other entities have
      the capability of generating polymers with properties that are at the level to
      enable the creation of novel pharmaceutical and medical products. Properties such
      as stimuli-responsiveness, site targeting, and chronotherapeutics are no longer
      figures of imaginations but have become a reality through utilizing processes of
      polymer refabrication. This article has sought to review the different techniques
      that have been employed in polymeric refabrication to produce superior products
      in the pharmaceutical and medical disciplines. Techniques such as grafting,
      blending, interpenetrating polymers networks, and synthesis of polymer complexes
      will be viewed from a pharmaceutical and medical perspective along with their
      synthetic process required to attain these products. In addition to this, each
      process will be evaluated according to its salient features, impeding features,
      and the role they play in improving current medical devices and procedures.

PMID- 23543610
TI  - The identification of three sizes of core proteins during the establishment of
      persistent hepatitis C virus infection in vitro.
AB  - Similar to Hepatitis C virus (HCV) infection in humans, HCVcc infection can also
      result in persistent and chronic infection. The core protein is a variable
      protein and exists in several sizes. Some sizes of core proteins have been
      reported to be related to chronic HCV infection. To study the possible role of
      the core protein in persistent HCV infection, a persistent HCVcc infection was
      established, and the expression of the core protein was analysed over the course
      of the infection. The results show that there are three sizes of core proteins
      (p24, p21 and p19) expressed during the establishment of persistent HCVcc
      infection. Of these, the p21 core protein is the mature form of the HCV core
      protein. The p24 core protein is the phosphorylated form of p21. The p19 core
      protein appears to be a functional by-product generated during the course of
      infection. These three core proteins are all localized in the cytoplasm and can
      be encapsidated into the HCV virion. The appearance of the p19 and p24 core
      proteins might be related to acute HCVcc infection and chronic infection
      respectively and may play an important role in the pathology of a HCV infection.

PMID- 23543611
TI  - In vitro evaluation of anthelmintic property of ethno-veterinary plant extracts
      against the liver fluke Fasciola gigantica.
AB  - The present study was envisaged to evaluate the efficacy of ethno-medicinal plant
      aqueous extracts such as Allium sativum, Lawsonia inermis, and Opuntia ficus
      indica in vitro in comparison with the chemotherapeutic agent, Oxyclozanide on
      Fasciola gigantica adults. The efficacy was evaluated by gross visual motility
      and mortality of F. gigantica with score index, light microscopic examination of
      carmine stained flukes and histopathology of treated flukes. Based on the in
      vitro trials conducted using above plant extracts at 1 percent, 2.5 percent and 5
      percent concentration, the extracts of O. ficus indica showed flukicidal effect
      at 2.5 and 5% concentration. However A. sativum and L. inermis were effective at
      5% concentration only. The study indicated the potential for developing herbal
      based anthelmintics to control F. gigantica in livestock.

PMID- 23543612
TI  - Microbes on the cliff: alpine cushion plants structure bacterial and fungal
      communities.
AB  - Plants affect the spatial distribution of soil microorganisms, but the influence
      of the local abiotic context is poorly documented. We investigated the effect of
      a single plant species, the cushion plant Silene acaulis, on habitat conditions,
      and microbial community. We collected soil from inside (In) and outside (Out) of
      the cushions on calcareous and siliceous cliffs in the French Alps along an
      elevation gradient (2,000-3,000 masl). The composition of the microbial
      communities was assessed by Capillary-Electrophoresis Single Strand Conformation
      Polymorphism (CE-SSCP). Univariate and multivariate analyses were conducted to
      characterize the response of the microbial beta-diversity to soil parameters
      (total C, total N, soil water content, [Formula: see text], and pH). Cushions
      affected the microbial communities, modifying soil properties. The fungal and
      bacterial communities did not respond to the same abiotic factors. Outside the
      cushions, the bacterial communities were strongly influenced by bedrock. Inside
      the cushions, the bacterial communities from both types of bedrock were highly
      similar, due to the smaller pH differences than in open areas. By contrast, the
      fungal communities were equally variable inside and outside of the cushions.
      Outside the cushions, the fungal communities responded weakly to soil pH. Inside
      the cushions, the fungal communities varied strongly with bedrock and elevation
      as well as increases in soil nutrients and water content. Furthermore, the
      dissimilarities in the microbial communities between the In and Out habitats
      increased with increasing habitat modification and environmental stress. Our
      results indicate that cushions act as a selective force that counteracts the
      influence of the bedrock and the resource limitations on the bacterial and fungal
      communities by buffering soil pH and enhancing soil nutrients. Cushion plants
      structure microbial communities, and this effect increases in stressful, acidic
      and nutrient-limited environments.

PMID- 23543613
TI  - A study on tubal recanalization.
AB  - OBJECTIVES: To study the various factors affecting the success rate of tubal
      recanalization and the reasons for failure of the procedure. METHODS: A
      retrospective study was conducted during 2000-2007 @ KIMS, Hubli. RESULTS: Of the
      25 subjects who underwent tubal recanalization, 44 % of women conceived and they
      were >35 years of age. Laparoscopically sterilized patients had better chances of
      conception (50 %) following reversal than those who were sterilized by Pomeroy's
      method (30 %). With post-reversal tubal length of >4 cm, pregnancy rate was 50 %.
      Isthumus-Isthumus and Isthumus-Ampullary anastomosis have 50 % success rates.
      CONCLUSION: Tubal recanalization by microsurgical technique is one of the methods
      to solve infertility after sterilization.

PMID- 23543609
TI  - Invasive candidiasis in intensive care units in China: a multicentre prospective
      observational study.
AB  - OBJECTIVES: To describe the epidemiology, microbiology and management of invasive
      Candida infection (ICI) in intensive care units (ICUs) in China. METHODS: A
      multicentre, prospective, observational study in 67 hospital ICUs across China.
      Patients were >=18 years old with clinical signs of infection and at least one of
      the following diagnostic criteria: (i) histopathological, cytopathological or
      microscopic confirmation of yeast cells from a normally sterile site; (ii) at
      least one peripheral blood culture positive for Candida; and (iii) positive
      Candida culture from a normally sterile site. The China-SCAN study is registered
      with ClinicalTrials.gov (NCT T01253954). RESULTS: ICI incidence was 0.32% (306
      patients/96,060 ICU admissions) and median time between ICU admission and
      diagnosis was 10.0 days. Candida albicans was the most prevalent single isolate
      (41.8% of patients), although non-albicans species accounted for the majority of
      infections. Diagnostic confirmation was based solely on at least one positive
      blood culture in 290 (94.8%) cases. Treatment was initiated after diagnostic
      confirmation in 166/268 (61.9%) patients. Triazoles (62.7%) and echinocandins
      (34.2%) were the most commonly used antifungal agents; first-line therapy was
      typically fluconazole (37.7%). The median duration of antifungal therapy was 14
      days. The mortality rate was 36.6% (112/306); the median time between diagnosis
      and death was 14.5 days. Mortality was higher in older individuals, those with
      solid tumours, those with recent invasive mechanical ventilation and those with a
      higher sequential organ failure assessment score at diagnostic confirmation.
      Susceptibility to first-line antifungals was associated with lower mortality than
      dose-dependent susceptibility or complete resistance (P=0.008). CONCLUSIONS: More
      infections were caused by non-albicans than Candida albicans strains. The
      majority of patients were treated only after diagnostic confirmation, rather than
      empirically. First-line antifungal susceptibility was associated with lower
      mortality.

PMID- 23543614
TI  - Proboscis lateralis of nose-a case report.
AB  - Lateral proboscis is a rare craniofacial malformation characterized by a
      rudimentary tubular, nose-like structure located off-center from the vertical
      midline of the face, and occur in association with a wide spectrum of other
      anomalies, including heminasal aplasia spectrum,mental retardation, callosal
      agenesis, heminasal hypoplasia, microphthalmia, and atypical clefting syndrome.
      Evaluation of a patient should include CT scan examination to look for growth of
      facial and skull bones. Reconstruction should start at an early age. Proboscis
      itself is the best option for heminose formation. Cartilaginous or bony support
      can be planned later in the late teens. Esthetic and psychological problems are
      often concern of the patient and families. Here we presented a male infant of 2
      months with Proboscis Lateralis. There was no e/o cleft lip or cleft palate.
      Staged repair was done at an early age to avoid anxiety of parents and to allow
      proportionate growth of nose and face.

PMID- 23543615
TI  - Platelet function testing and tailored antiplatelet therapy.
AB  - Dual antiplatelet therapy, consisting of aspirin and a P2Y12 receptor inhibitor,
      has dramatically reduced the incidence of atherothrombotic events for patients
      with acute coronary syndrome and those undergoing a percutaneous coronary
      intervention (PCI). However, the platelet inhibitory effect of clopidogrel, the
      most commonly used P2Y12 inhibitor, is variable between patients. Patients
      exhibiting high platelet reactivity (HPR) despite clopidogrel treatment are at
      higher risk of recurrent atherothrombotic events after PCI. In order to reduce
      the incidence of HPR, the more potent P2Y12 receptor inhibitors prasugrel and
      ticagrelor are used. However, these drugs increase the risk of bleeding. As there
      is evidence of a therapeutic window for platelet inhibition, platelet function
      tests could be helpful for tailoring antiplatelet therapy based on the patient's
      thrombotic and bleeding risk. In the present article, we review the most commonly
      used platelet function tests and the current evidence for tailoring of
      antiplatelet therapy in PCI patients.

PMID- 23543616
TI  - CASK and CaMKII function in the mushroom body alpha'/beta' neurons during
      Drosophila memory formation.
AB  - Ca(2+)/CaM serine/threonine kinase II (CaMKII) is a central molecule in
      mechanisms of synaptic plasticity and memory. A vital feature of CaMKII in
      plasticity is its ability to switch to a calcium (Ca(2+)) independent
      constitutively active state after autophosphorylation at threonine 287 (T287). A
      second pair of sites, T306 T307 in the calmodulin (CaM) binding region once
      autophosphorylated, prevent subsequent CaM binding and inactivates the kinase
      during synaptic plasticity and memory. Recently a synaptic molecule called
      Ca(2+)/CaM-dependent serine protein kinase (CASK) has been shown to control both
      sets of CaMKII autophosphorylation events and hence is well poised to be a key
      regulator of memory. We show deletion of full length CASK or just its CaMK-like
      and L27 domains disrupts middle-term memory (MTM) and long-term memory (LTM),
      with CASK function in the alpha'/beta' subset of mushroom body neurons being
      required for memory. Likewise directly changing the levels of CaMKII
      autophosphorylation in these neurons removed MTM and LTM. The requirement of CASK
      and CaMKII autophosphorylation was not developmental as their manipulation just
      in the adult alpha'/beta' neurons was sufficient to remove memory. Overexpression
      of CASK or CaMKII in the alpha'/beta' neurons also occluded MTM and LTM.
      Overexpression of either Drosophila or human CASK in the alpha'/beta' neurons of
      the CASK mutant completely rescued memory, confirming that CASK signaling in
      alpha'/beta' neurons is necessary and sufficient for Drosophila memory formation
      and that the neuronal function of CASK is conserved between Drosophila and human.
      At the cellular level CaMKII overexpression in the alpha'/beta' neurons increased
      activity dependent Ca(2+) responses while reduction of CaMKII decreased it.
      Likewise reducing CASK or directly expressing a phosphomimetic CaMKII T287D
      transgene in the alpha'/beta' similarly decreased Ca(2+) signaling. Our results
      are consistent with CASK regulating CaMKII autophosphorylation in a pathway
      required for memory formation that involves activity dependent changes in Ca(2+)
      signaling in the alpha'/beta' neurons.

PMID- 23543617
TI  - MicroRNAs in Ewing Sarcoma.
AB  - MicroRNAs (miRs) have emerged recently as important regulators of gene expression
      in the cell. Frequently dysregulated in cancer, miRs have shed new light on
      molecular mechanisms of oncogenesis, and have generated substantial interest as
      biomarkers, and novel therapeutic agents and targets. Recently, a number of
      studies have examined miR biology in Ewing sarcoma. Findings indicate that
      alterations in miR expression in Ewing Sarcoma are widespread, involve both
      EWS/Ets oncogenic fusion-dependent and independent mechanisms, and contribute to
      malignant phenotypes. miRs with prognostic potential have been identified, and
      several preclinical studies suggest that miR manipulation could be
      therapeutically useful in this aggressive disease. These and future studies of
      miR biology stand to expand our understanding of Ewing sarcoma pathogenesis, and
      may identify new biomarkers and treatment options.

PMID- 23543618
TI  - The Corpus Callosum Wallerian Degeneration in the Unilateral Brain Tumors:
      Evaluation with Diffusion Tensor Imaging (DTI).
AB  - PURPOSE: The purpose of this study was to evaluate whether DTI could demonstrate
      the water diffusivity changes in the corpus callosum (CC), which were not visible
      on the morphologic imaging in patients with glioblastoma multiforme (GBM) and
      brain metastases with no midline CC infiltration. MATERIALS AND METHODS: Twenty
      seven patients with treatment naive unilateral GBM and eleven patients with a
      solitary brain metastasis with no midline CC infiltration underwent DTI. Ten
      controls with normal brain MRI were also included. Based on the tensors, the
      principal diffusion directions, the anisotropy values, and the prior information
      about the diffusivity pattern in CC, a similarity measure was proposed.
      Subsequently, the CC was automatically divided into the Witelson subdivisions.
      RESULTS: We observed significantly decreased fractional anisotropy values in all
      the regions of CC in the patients with GBM and metastases as compared to those in
      the controls. The mean diffusivity values showed a significant increase in all
      the regions of CC, except the splenium in patients with GBM and the isthmus in
      the patients with metastases, as compared to that in the controls respectively.
      CONCLUSION: In conclusion, DTI is more sensitive than the morphologic MR imaging
      in the evaluation of changes within the CC, in brain tumours which do not
      infiltrate the CC. However, these changes of the DTI metrics in the CC are due to
      a Wallerian degeneration rather than a tumour infiltration, as was shown by our
      results, as similar changes were seen in the GBM as well as the non-infiltrating
      metastases patients.

PMID- 23543619
TI  - Psychosocial aspects of child and adolescent obesity.
AB  - In addition to counselling families about regular physical activity and healthy
      nutrition, clinicians need to identify and help them to address the psychosocial
      factors that may be contributing to their child's or adolescent's obesity.
      Affected individuals may suffer from depression, low self-esteem, bullying, and
      weight bias, experiences that can make achieving desired health outcomes more
      difficult. Clinicians should try to identify these underlying stressors and
      ensure that appropriate counselling is implemented.

PMID- 23543620
TI  - Asynchronous variational integration using continuous assumed gradient elements.
AB  - Asynchronous variational integration (AVI) is a tool which improves the numerical
      efficiency of explicit time stepping schemes when applied to finite element
      meshes with local spatial refinement. This is achieved by associating an
      individual time step length to each spatial domain. Furthermore, long-term
      stability is ensured by its variational structure. This article presents AVI in
      the context of finite elements based on a weakened weak form (W2) Liu (2009) [1],
      exemplified by continuous assumed gradient elements Wolff and Bucher (2011) [2].
      The article presents the main ideas of the modified AVI, gives implementation
      notes and a recipe for estimating the critical time step.

PMID- 23543621
TI  - The effect of hydro-ethanolic extract of Achillea millefolium on muscarinic
      receptors of guinea pig tracheal smooth muscle.
AB  - OBJECTIVE: To investigate one possible mechanism for the observed relaxant effect
      of A. millefolium (Achillea millefolium), in the present study the inhibitory
      effect of the extract of this plant on muscarinic receptors was examined.
      MATERIALS AND METHODS: The effects of three concentrations of aqueous-ethanolic
      extract, 10 nM atropine, and saline on muscarinic receptors were tested in three
      conditions: In non incubated tracheal smooth muscle (group 1), tracheal chain
      incubated with propranolol and chlorpheniramine (group 2), and the one incubated
      with propranolol (group 3). RESULTS: The EC50 obtained in the presence of all
      three concentrations of the extract were significantly higher compared to saline
      in groups 2 and 3 (P < 0.001 and P < 0.01 in group 2 and 3 respectively). The
      EC50 obtained in the presence of all concentrations of the extract in group 2
      were significantly improved compared to groups 1 and 3 (P < 0.05 to P < 0.001).
      The maximum responses to methacholine in presence of only the higher
      concentration of the extract (0.8 mg/ml) was significantly lower than that of
      saline in groups 1 (P < 0.05). There was neither significant difference between
      slopes of methacholine-response curves obtained in the presence of different
      concentrations of the extract and that of saline nor between the three groups.
      The values of (CR-1), obtained in the presence of all concentrations of the
      extract, were significantly lower compared to atropine in the first group but
      were not significantly different in other groups. The values of (CR-1) obtained
      in the presence of all concentrations of the extract were significantly improved
      in groups 2, compared to groups 1 and 3 (P < 0.05 to P < 0.001). CONCLUSION:
      These results showed an inhibitory effect for the extract of A. millefolium on
      muscarinic receptors of tracheal smooth muscle. A histamine (H1) receptor
      blockade was also suggested for the extract.

PMID- 23543622
TI  - "Toxic Pancreatitis with an Intra-Abdominal Abscess which was Caused by
      Organophosphate Poisoning (OP)".
AB  - Organophosphate insecticides are the potent inhibitors of the
      acetylcholinesterase enzyme which lead to an increased acetylcholine activity,
      which are responsible for symptoms such as abdominal pain, diarrhoea, vomiting
      and hypersalivation. We are reporting on a young male with acute organophosphate
      poisoning, who presented with unusual complications like toxic pancreatitis with
      an intraabdominal abscess.

PMID- 23543623
TI  - Extreme Depletion of PIP3 Accompanies the Increased Life Span and Stress
      Tolerance of PI3K-null C. elegans Mutants.
AB  - The regulation of animal longevity shows remarkable plasticity, in that a variety
      of genetic lesions are able to extend lifespan by as much as 10-fold. Such
      studies have implicated several key signaling pathways that must normally limit
      longevity, since their disruption prolongs life. Little is known, however, about
      the proximal effectors of aging on which these pathways are presumed to converge,
      and to date, no pharmacologic agents even approach the life-extending effects of
      genetic mutation. In the present study, we have sought to define the downstream
      consequences of age-1 nonsense mutations, which confer 10-fold life extension to
      the nematode Caenorhabditis elegans - the largest effect documented for any
      single mutation. Such mutations insert a premature stop codon upstream of the
      catalytic domain of the AGE-1/p110alpha subunit of class-I PI3K. As expected, we
      do not detect class-I PI3K (and based on our sensitivity, it constitutes <14% of
      wild-type levels), nor do we find any PI3K activity as judged by immunodetection
      of phosphorylated AKT, which strongly requires PIP3 for activation by upstream
      kinases, or immunodetection of its product, PIP3. In the latter case, the upper
      95%-confidence limit for PIP3 is 1.4% of the wild-type level. We tested a variety
      of commercially available PI3K inhibitors, as well as three phosphatidylinositol
      analogs (PIAs) that are most active in inhibiting AKT activation, for effects on
      longevity and survival of oxidative stress. Of these, GDC-0941, PIA6, and PIA24
      (each at 1 or 10 MUM) extended lifespan by 7-14%, while PIAs 6, 12, and 24 (at 1
      or 10 MUM) increased survival time in 5 mM peroxide by 12-52%. These effects may
      have been conferred by insulinlike signaling, since a reporter regulated by the
      DAF-16/FOXO transcription factor, SOD-3::GFP, was stimulated by these PIAs in the
      same rank order (PIA24 > PIA6 > PIA12) as lifespan. A second reporter,
      PEPCK::GFP, was equally activated (~40%) by all three.

PMID- 23543624
TI  - Fatal anaphylactic reaction to iron sucrose in pregnancy.
AB  - Iron-deficiency anemia in pregnancy can have serious deleterious effects for both
      mother and fetus. Parenteral iron therapy in iron-deficiency anemia is
      recommended in patients where oral iron therapy is ineffective due to
      malabsorption states and non-compliance. Compared to oral iron therapy,
      intravenous iron results in much more rapid resolution of iron-deficiency anemia
      with minimal adverse reactions. Iron sucrose has a favorable safety profile and
      is an alternative to other forms of parenteral iron therapy in correction of iron
      stores depletion. Immune mechanisms and iron agent releasing bioactive, partially
      unbound iron into the circulation, resulting in oxidative stress appears to cause
      severe adverse reactions. Although iron sucrose has a favorable safety profile in
      comparison to other parenteral iron preparations, this report highlights a fatal
      anaphylactic shock to iron sucrose in a pregnant woman with severe iron
      deficiency non-compliant to oral iron therapy.

PMID- 23543625
TI  - Maternal anemia in various trimesters and its effect on newborn weight and
      maturity: an observational study.
AB  - BACKGROUND: Anemia has been a very important nutritional disorder in the world.
      India has reported high prevalence of anemia in pregnancy. Most of the articles
      have reported an adverse pregnancy outcome related to anemia. Of late, reports
      are emerging suggesting anemia could be indeed beneficial. Apart from that, there
      was no consistency in the timing of hemoglobin considered for analysis. Hence, we
      designed an observational study to look into these aspects. METHODS: 1000 mothers
      admitted for delivery were recruited and their hemoglobin was measured.
      Hemoglobin in previous trimesters was noted from their antenatal record. We
      followed up these mothers till delivery and looked into the gestation and birth
      weight of the babies. Descriptive statistics was used for baseline
      characteristics. Comparison of means was done using Student's t-test. Qualitative
      variables were compared using Fisher's exact test. RESULTS: More than 50% of the
      mothers were anemic at some point of time during their pregnancy and 39% of the
      mothers were anemic throughout. Mean birth weight of babies born to anemic
      mothers was marginally lower compared to that of babies born to nonanemic
      mothers. This difference was statistically significant. There was 6.5% increase
      in the incidence of low birth weight babies and 11.5% increase in preterm
      deliveries in mothers who were anemic in their third trimester. CONCLUSIONS: The
      incidence of low birth weight babies was significantly more in mothers who were
      anemic in their third trimester. Preterm deliveries occurred more frequently in
      mothers who were anemic in their second and third trimesters. Higher hemoglobin
      did not show any effect on either birth weight or gestation in our study.

PMID- 23543626
TI  - Keratitis with Elizabethkingia meningoseptica occurring after contact lens wear:
      a case report.
AB  - To report keratitis with Elizabethkingia meningoseptica, which occurred in a
      healthy patient after wearing contact lenses for 6 months. A 24-year-old male
      patient visited our hospital with ocular pain. This patient had a history of
      wearing soft contact lenses for 6 months, about 10 hours per day. At initial
      presentation, slit lamp examination showed corneal stromal infiltrations and
      small epithelial defect. Microbiological examinations were performed from corneal
      scrapings, contact lenses, and the contact lens case and solution. The culture
      results from contact lenses, contact lens case and solution were all positive for
      Elizabethkingia meningoseptica. Thus, we could confirm that the direct cause of
      keratitis was contamination of the contact lenses. The patient was treated with
      0.3% gatifloxacin. After treatment, the corneal epithelial defect was completely
      healed, and a slight residual subepithelial corneal opacity was observed. We
      diagnosed keratitis with Elizabethkingia meningoseptica in a healthy young male
      wearing soft contact lenses. We conclude that Elizabethkingia meningoseptica
      should be considered as a rare but potential pathogen for lens-related keratitis
      in a healthy host.

PMID- 23543627
TI  - Extracellular Methemoglobin Mediated Early ROS Spike Triggers Osmotic Fragility
      and RBC Destruction: An Insight into the Enhanced Hemolysis During Malaria.
AB  - Malaria infection is known to cause severe hemolysis due to production of
      abnormal RBCs and enhanced RBC destruction through apoptosis. Infected RBC lysis
      exposes uninfected RBC to the large amount of pro-oxidant molecules such as
      methemoglobin. Methemoglobin (MetHb) exposure dose dependently makes RBCs
      susceptible to osmotic stress and causes hemolysis. MetHb mediated oxidative
      stress in RBC correlated well with osmotic fragility and hemolysis.
      Interestingly, a reactive oxygen species (ROS) spike at 15 min was responsible
      for the observed effects on RBC cells. Two natural antioxidants N-acetyl cysteine
      and mannitol protected the RBC from MetHb-mediated defects, which clearly
      indicated involvement of oxidative stress in the process. MetHb due to its pseudo
      peroxidase activity produces ROS in the external microenvironment. Therefore,
      classical peroxidase inhibitors were tested to probe peroxidase activity mediated
      ROS production with defects in RBCs. Clotrimazole (CLT), which irreversibly
      inactivates the MetHb (CLT-MetHb) and abolishes peroxidase activity, did not
      produce significant ROS outside RBC and was inefficient to cause osmotic
      fragility and hemolysis. Hence, initiating a chain reaction, MetHb released from
      ruptured RBC produces significant ROS in the external microenvironment to make
      RBC membrane leaky and enhanced hemolysis. Together data presented in the current
      work explored the role of MetHb in accelerated humorless during malaria which
      could be responsible for severe outcomes of pathological disorders.

PMID- 23543628
TI  - On two new species of the genus Cornudescoides Kulkarni, 1969 (Monogenea:
      Ancyrocephalinae) from a freshwater fish Mystus vittatus from Meerut (U.P.),
      India.
AB  - During study of freshwater monogeneans of Meerut region, we came across five
      infected specimen of fish Mystus vittatus, infected with monogeneans belonging to
      the genus Cornudescoides Kulkarni 1969. On subsequent study, the worms appear new
      to us and are described here in as such. C. kulkarnii n. sp. is characterized by
      four pairs of head organs, nut cracker shaped accessory piece of cirrus,
      capitulum or patches with proximal conical protruberance, longer inner root of
      dorsal anchor and difference in shape and extension of dorsal bars. While C.
      susanii n. sp. is characterized by presence of seven pairs of head organs,
      caliper like accessory piece of cirrus, longer and inwardly curved lateral hooks,
      prominently protruded outer roots and larger inner roots of dorsal anchor.

PMID- 23543629
TI  - Pharmacokinetic characterization of CK2 inhibitor CX-4945.
AB  - Over-expression of protein kinase CK2 is highly linked to the survival of cancer
      cells and the poor prognosis of patients with cancers. CX-4945, a potent and
      selective orally bioavailable ATP-competitive inhibitor of CK2, inhibits the
      oncogenic cellular events such as proliferation and angiogenesis, and the
      increase of tumor growth in mouse xenograft model. In this study, the
      pharmacokinetic information about CX-4945 was provided; at 10 MUM, CX-4945 with
      high stability in human and rat liver microsome exhibited low percentage of
      inhibition (<10 %) in CYP450 isoforms (1A2, 2C19, 3A4), but considerable
      inhibition (~70 %) in CYP450 2C9 and 2D6. In hERG potassium channel inhibition
      assay, CX-4945 exhibited relatively low inhibition rate. Additionally, CX-4945
      showed high MDCK cell permeability (>10 * 10(-6) cm/s) and above 98 % of plasma
      protein binding in the rat. After intravenous administration, Vss (1.39 l/kg) and
      extremely low CL (0.08 l/kg/h) were observed. Moreover, orally administrated CX
      4945 showed high bioavailability (>70 %) and these data might be related to the
      MDCK cell permeability results.

PMID- 23543630
TI  - The ameliorating effects of 5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H
      chromene-4-one, an oroxylin A derivative, against memory impairment and
      sensorimotor gating deficit in mice.
AB  - We previously reported that oroxylin A, a gamma-aminobutyric acid A (GABAA)
      receptor antagonist, ameliorates drugs-induced memory impairments. We synthesized
      several oroxylin A derivatives in efforts to find a substance that has pro
      cognitive effects as well as improves sensorimotor gating. The aim of the present
      study is to investigate the effect of a novel oroxylin A derivative, 5,7
      dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on
      pharmacological models of schizophrenia, which exhibit memory impairment and
      sensorimotor gating deficit. Memory impairment was induced by scopolamine, a
      muscarinic receptor antagonist, or MK-801, an N-methyl-D-aspartate receptor
      antagonist. Sensorimotor gating deficits were induced by MK-801 and measured by
      prepulse inhibition (PPI) of the acoustic startle response task. DMPC treatment
      (20 mg/kg) significantly attenuated scopolamine- or MK-801-induced memory
      impairment and it even enhanced cognitive performance of normal animals.
      Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the
      acoustic startle response task. In an in vitro study, DMPC (20 MUM) inhibited
      intracellular Cl(-) influx induced by muscimol, a selective GABAA receptor
      agonist. These results suggest that DMPC would be a potential candidate for
      alleviating cognitive dysfunction and sensorimotor gating deficits in
      schizophrenia, and that its effects may be mediated, in part, via blockade of the
      GABAergic neurotransmitter system.

PMID- 23543631
TI  - Progress in the studies on tryptanthrin, an alkaloid of history.
AB  - Tryptanthrin, an indoloquinazoline alkaloid, was first obtained by sublimation of
      natural indigo and later isolated from the culture of fungus Candida lipolytica
      and a variety of other natural sources. Tryptanthrin showed a variety of
      intriguing biological properties such as antibacterial, antifungal,
      antiprotozoal, and antiparasitic activities, inhibitory activities against COX-2,
      5-LOX, NO synthase and PGE(2) expression, as well as cytotoxic and antitumor
      activities. Present review covers recent studies on the natural sources,
      biological activities and mechanisms of their actions, synthesis, structure
      activity relationship, and metabolism of tryptanthrin.

PMID- 23543632
TI  - Design, synthesis, in vitro cytotoxicity evaluation and structure-activity
      relationship of goniothalamin analogs.
AB  - A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from
      commercially available (3,4-dihydro-2H-pyran-2-yl)methanol/5
      (hydroxymethyl)dihydrofuran-2(3H)-one in three steps with good to moderate
      overall yields and their cytotoxicity against lymphoblastic leukemic T cell line
      (Jurkat E6.1) have been evaluated. Among the synthesized analogs, (Z)
      Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 MUM).
      Structure-activity relationship study indicates that introducing substituent in
      phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the
      ring size of lactones (from six to five member) do not increase the cytotoxicity.

PMID- 23543633
TI  - Healthy active living: Physical activity guidelines for children and adolescents.
AB  - The epidemic of childhood obesity is rising globally. Although the risk factors
      for obesity are multifactorial, many are related to lifestyle and may be amenable
      to intervention. These factors include sedentary time and non-exercise activity
      thermogenesis, as well as the frequency, intensity, amounts and types of physical
      activity. Front-line health care practitioners are ideally suited to monitor
      children, adolescents and their families' physical activity levels, to evaluate
      lifestyle choices and to offer appropriate counselling. This statement presents
      guidelines for reducing sedentary time and for increasing the level of physical
      activity in the paediatric population. Developmentally appropriate physical
      activity recommendations for infants, toddlers, preschoolers, children and
      adolescents are provided. Advocacy strategies for promoting healthy active living
      at the local, municipal, provincial/territorial and federal levels are included.

PMID- 23543634
TI  - On the relevance of assumptions associated with classical factor analytic
      approaches.
AB  - A personal trait, for example a person's cognitive ability, represents a
      theoretical concept postulated to explain behavior. Interesting constructs are
      latent, that is, they cannot be observed. Latent variable modeling constitutes a
      methodology to deal with hypothetical constructs. Constructs are modeled as
      random variables and become components of a statistical model. As random
      variables, they possess a probability distribution in the population of
      reference. In applications, this distribution is typically assumed to be the
      normal distribution. The normality assumption may be reasonable in many cases,
      but there are situations where it cannot be justified. For example, this is true
      for criterion-referenced tests or for background characteristics of students in
      large scale assessment studies. Nevertheless, the normal procedures in
      combination with the classical factor analytic methods are frequently pursued,
      despite the effects of violating this "implicit" assumption are not clear in
      general. In a simulation study, we investigate whether classical factor analytic
      approaches can be instrumental in estimating the factorial structure and
      properties of the population distribution of a latent personal trait from
      educational test data, when violations of classical assumptions as the
      aforementioned are present. The results indicate that having a latent non-normal
      distribution clearly affects the estimation of the distribution of the factor
      scores and properties thereof. Thus, when the population distribution of a
      personal trait is assumed to be non-symmetric, we recommend avoiding those factor
      analytic approaches for estimation of a person's factor score, even though the
      number of extracted factors and the estimated loading matrix may not be strongly
      affected. An application to the Progress in International Reading Literacy Study
      (PIRLS) is given. Comments on possible implications for the Programme for
      International Student Assessment (PISA) complete the presentation.

PMID- 23543635
TI  - Prevalence of High and Low Level Mupirocin Resistance among Staphylococcal
      Isolates from Skin Infection in a Tertiary Care Hospital.
AB  - BACKGROUND: Mupirocin has been used for the treatment of skin infections and for
      the eradication of the nasal carriage of Methicillin -resistant Staphylococcus
      aureus (MRSA). The increased use of this antibiotic has been accompanied by its
      resistance, resulting in treatment failures. OBJECTIVE: This study was aimed at
      determining the prevalences of low and high level Mupirocin resistance among the
      clinical isolates of Staphylococcus species which were obtained from pyogenic
      infections. MATERIAL AND METHOD: Clinical samples such as wound swabs, tissues
      and pus which were submitted to the microbiology laboratory during a period of
      six months were screened for the growth of Staphylococcus species, which were
      identified as Staphylococcus aureus and Coagulase negative Staphylococcus species
      by the routine microbiological procedures. All the isolates were tested for their
      Mupirocin susceptibilities by using 5 and 200 MUg discs and their resistance was
      confirmed from their Minimum Inhibitory Concentrations (MICs). RESULT: Out of 400
      samples, 150 samples grew Staphylococcus species, of which 113 were
      Staphylococcus aureus and 37 were Coagulase negative Staphylococcus (CoNS). Only
      5(3.3%) mupirocin resistant Staphylococcus species: three high level and two low
      level strains were detected. The MICs for the two low level and three high level
      Mupirocin resistant strains were 256 mg/L and >=512mg/L each respectively.
      CONCLUSION: We conclude that the screening for mupirocin resistance, in terms of
      high-level and low-level resistance among the Staphylococcus species from
      patients with skin and soft tissue infections is warranted and that it is
      important for the clinicians in selecting the appropriate, empirical, topical,
      antimicrobial therapy. It also provides useful information about the prevalence
      of these resistant pathogens.

PMID- 23543636
TI  - Pseudomyxoma peritonea: uncommon presentation.
AB  - Pseudomyxoma peritonei is rare being characterized by intraperitoneal
      accumulation of mucinous ascites produced by neoplastic cells, mostly originating
      from a perforated appendiceal adenoma. The clinical presentatation of the disease
      is variable, and preoperative diagnosis is often difficult. We describe the
      clinical case of a 60-year-old patient who presentated predominantly with
      urological symptoms. CECT revealed an appendiceal lesion infiltrating and
      projecting into the urinary bladder. Surgical cytoreduction was performed and
      patient remains symptomatically better on follow up.

PMID- 23543637
TI  - Detection of HPV by PCR-A Novel Step in the Prevention of Cancer Cervix.
AB  - OBJECTIVES: (1) To compare the efficacy of Pap smear and HPV PCR for detection of
      CIN; and (2) To study the distribution of HPV genotypes. METHODS: One hundred
      women presenting at the female Outpatient Department with unhealthy cervices were
      subjected to a detailed history, clinical examination, Pap smear, HPV DNA PCR
      test, and colposcopic-directed biopsy (where indicated). RESULTS: This study has
      shown that there is a strong association of HPV infection with higher grades of
      CIN (100 % in patients with CIN 2, CIN 3, and CIS). The detection of CIN by HPV
      PCR was more accurate than by Pap smear. The most prevalent HPV genotype found in
      our study was HPV 16. CONCLUSION: The advent of HPV testing has opened the doors
      for more accurate cervical cancer surveillance strategies than Pap smear. Early
      detection and treatment of CIN will considerably reduce the incidence of cervical
      cancer.

PMID- 23543638
TI  - Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and
      hexokinase activity in human brain.
AB  - In hyperglycemia, glucagon-like peptide-1 (GLP-1) lowers brain glucose
      concentration together with increased net blood-brain clearance and brain
      metabolism, but it is not known whether this effect depends on the prevailing
      plasma glucose (PG) concentration. In hypoglycemia, glucose depletion potentially
      impairs brain function. Here, we test the hypothesis that GLP-1 exacerbates the
      effect of hypoglycemia. To test the hypothesis, we determined glucose transport
      and consumption rates in seven healthy men in a randomized, double-blinded
      placebo-controlled cross-over experimental design. The acute effect of GLP-1 on
      glucose transfer in the brain was measured by positron emission tomography (PET)
      during a hypoglycemic clamp (3 mM plasma glucose) with (18)F-fluoro-2-deoxy
      glucose (FDG) as tracer of glucose. In addition, we jointly analyzed
      cerebrometabolic effects of GLP-1 from the present hypoglycemia study and our
      previous hyperglycemia study to estimate the Michaelis-Menten constants of
      glucose transport and metabolism. The GLP-1 treatment lowered the vascular volume
      of brain tissue. Loading data from hypo- to hyperglycemia into the Michaelis
      Menten equation, we found increased maximum phosphorylation velocity (V max) in
      the gray matter regions of cerebral cortex, thalamus, and cerebellum, as well as
      increased blood-brain glucose transport capacity (T max) in gray matter, white
      matter, cortex, thalamus, and cerebellum. In hypoglycemia, GLP-1 had no effects
      on net glucose metabolism, brain glucose concentration, or blood-brain glucose
      transport. Neither hexokinase nor transporter affinities varied significantly
      with treatment in any region. We conclude that GLP-1 changes blood-brain glucose
      transfer and brain glucose metabolic rates in a PG concentration-dependent
      manner. One consequence is that hypoglycemia eliminates these effects of GLP-1 on
      brain glucose homeostasis.

PMID- 23543639
TI  - A prospective randomized comparative study of vicryl rapide versus chromic catgut
      for episiotomy repair.
AB  - BACKGROUND AND OBJECTIVES: A significant number of women experience perineal
      trauma following vaginal deliveries and they require stitches. This may result in
      perineal pain, dyspareunia and faulty healing. The type of suture material which
      is used, will influence these factors. This study was conducted to compare the
      impact of two absorbable suture materials which were used for episiotomy repair,
      namely vicryl rapide and chromic catgut in relation to a short term maternal
      morbidity, in terms of the perineal pain and the wound healing. METHODS: This was
      a prospective, randomized study which was conducted in the hospitals which were
      attached to JJMMC, Davangere. Four hundred women with episiotomies were randomly
      allocated to repair with either vicrylrapide or chromic catgut (200 each). The
      outcome measures which were assessed were perineal pain and wound healing at 24
      48 hours, 3-5 days and 6 weeks postpartum. RESULTS: The two groups were similar
      at the trial entry. As compared to the chromic catgut group, the vicryl rapide
      group was associated with less pain (32.5% vs 57%) and a less need for analgesia
      (15.5% vs 0.5) at 3-5 days. There was also a signifi- cant reduction in the wound
      indurations, uncomfortable stitches and wound dehiscence (4% vs 13.5%) and a
      better wound healing (p<0.05 significant) in the vicrylrapide group. No
      significant difference was noted in the perineal pain at 6 weeks postpartum.
      Wound infections (3.5%) and wound resuturing (2%) were seen in the chromic catgut
      group and they were absent in the vicrylrapide group. INTERPRETATION AND
      CONCLUSION: So, this study concluded that vicrylrapide was the ideal suture
      material for episiotomy repair, which resulted in less perineal pain and a better
      wound healing.

PMID- 23543641
TI  - Metaheuristics for the dynamic stochastic dial-a-ride problem with expected
      return transports.
AB  - The problem of transporting patients or elderly people has been widely studied in
      literature and is usually modeled as a dial-a-ride problem (DARP). In this paper
      we analyze the corresponding problem arising in the daily operation of the
      Austrian Red Cross. This nongovernmental organization is the largest organization
      performing patient transportation in Austria. The aim is to design vehicle routes
      to serve partially dynamic transportation requests using a fixed vehicle fleet.
      Each request requires transportation from a patient's home location to a hospital
      (outbound request) or back home from the hospital (inbound request). Some of
      these requests are known in advance. Some requests are dynamic in the sense that
      they appear during the day without any prior information. Finally, some inbound
      requests are stochastic. More precisely, with a certain probability each outbound
      request causes a corresponding inbound request on the same day. Some stochastic
      information about these return transports is available from historical data. The
      purpose of this study is to investigate, whether using this information in
      designing the routes has a significant positive effect on the solution quality.
      The problem is modeled as a dynamic stochastic dial-a-ride problem with expected
      return transports. We propose four different modifications of metaheuristic
      solution approaches for this problem. In detail, we test dynamic versions of
      variable neighborhood search (VNS) and stochastic VNS (S-VNS) as well as modified
      versions of the multiple plan approach (MPA) and the multiple scenario approach
      (MSA). Tests are performed using 12 sets of test instances based on a real road
      network. Various demand scenarios are generated based on the available real data.
      Results show that using the stochastic information on return transports leads to
      average improvements of around 15%. Moreover, improvements of up to 41% can be
      achieved for some test instances.

PMID- 23543642
TI  - Lessons learnt in Europe on tuberculosis surveillance, outbreaks and BCG
      vaccination in 2011.

PMID- 23543640
TI  - Morpho-functional architecture of the Golgi complex of neuroendocrine cells.
AB  - In neuroendocrine cells, prohormones move from the endoplasmic reticulum to the
      Golgi complex (GC), where they are sorted and packed into secretory granules. The
      GC is considered the central station of the secretory pathway of proteins and
      lipids en route to their final destination. In most mammalian cells, it is formed
      by several stacks of cisternae connected by tubules, forming a continuous ribbon.
      This organelle shows an extraordinary structural and functional complexity, which
      is exacerbated by the fact that its architecture is cell type specific and also
      tuned by the functional status of the cell. It is, indeed, one the most beautiful
      cellular organelles and, for that reason, perhaps the most extensively
      photographed by electron microscopists. In recent decades, an exhaustive
      dissection of the molecular machinery involved in membrane traffic and other
      Golgi functions has been carried out. Concomitantly, detailed morphological
      studies have been performed, including 3D analysis by electron tomography, and
      the precise location of key proteins has been identified by immunoelectron
      microscopy. Despite all this effort, some basic aspects of Golgi functioning
      remain unsolved. For instance, the mode of intra-Golgi transport is not known,
      and two opposing theories (vesicular transport and cisternal maturation models)
      have polarized the field for many years. Neither of these theories explains all
      the experimental data so that new theories and combinations thereof have recently
      been proposed. Moreover, the specific role of the small vesicles and tubules
      which surround the stacks needs to be clarified. In this review, we summarize our
      current knowledge of the Golgi architecture in relation with its function and the
      mechanisms of intra-Golgi transport. Within the same framework, the
      characteristics of the GC of neuroendocrine cells are analyzed.

PMID- 23543643
TI  - Differences between asthmatics and nonasthmatics hospitalised with influenza A
      infection.

PMID- 23543644
TI  - Antithrombotics in pulmonary hypertension: more work needed before we turn to
      newer agents!

PMID- 23543645
TI  - Genetic predisposition to sarcoidosis: another brick in the wall.

PMID- 23543646
TI  - Treatment of pulmonary hypertension in interstitial lung disease: do not throw
      out the baby with the bath water.

PMID- 23543647
TI  - A molecular comparison of microbial communities in bronchiectasis and cystic
      fibrosis.

PMID- 23543648
TI  - Exacerbation of respiratory symptoms in COPD patients may not be exacerbations of
      COPD.

PMID- 23543649
TI  - Tracheal oxalosis associated with Aspergillus niger tracheobronchitis.

PMID- 23543651
TI  - Urethane increases reactive oxygen species and activates extracellular signal
      regulated kinase in RAW 264.7 macrophages and A549 lung epithelial cells.
AB  - Urethane, which is used as an anesthetic for animal experiments, causes
      inflammation and cancer in the lung. BALB/c mice received 1 mg/g of urethane once
      a week for four consecutive weeks via intraperitoneal injections developed
      interstitial infiltration of inflammatory cells and tumors in the lung. However,
      the intracellular signaling events which urethane causes inflammation and cancer
      are largely unknown. Here we show that urethane caused overproduction of reactive
      oxygen species (ROS) in RAW 264.7 macrophages and A549 lung epithelial cells.
      Pretreatment of these cells with the antioxidant N-acetylcysteine attenuated the
      urethane-induced ROS production. Urethane increased heme oxygenase-1 expression
      to protect these cells from cytotoxicity caused by overproduced ROS. In addition,
      urethane activated extracellular signal-regulated kinase (ERK) in both cell
      types. Overall, our data imply that urethane stimulates ROS production and ERK
      activation in macrophages and lung epithelial cells, and the overproduced ROS and
      activated ERK may promote tumor formation in the lung.

PMID- 23543652
TI  - Long-acting injectable formulations of antipsychotic drugs for the treatment of
      schizophrenia.
AB  - Antipsychotic drugs have been used to treat patients with schizophrenia and other
      psychotic disorders. Long-acting injectable antipsychotic drugs are useful for
      improving medication compliance with a better therapeutic option to treat
      patients who lack insight or adhere poorly to oral medication. Several long
      acting injectable antipsychotic drugs are clinically available. Haloperidol
      decanoate and fluphenazine decanoate are first-generation depot drugs, but the
      use of these medicines has declined since the advent of second-generation depot
      agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine
      pamoate. The second-generation depot drugs are better tolerated and have fewer
      adverse neurological side effects. Long-acting injectable risperidone, the first
      depot formulation of an atypical antipsychotic drug, was prepared by
      encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate
      is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a
      microcrystalline salt of olanzapine and pamoic acid suspended in aqueous
      solution. This review summarizes the characteristics and recent research of
      formulations of each long-acting injectable antipsychotic drug.

PMID- 23543653
TI  - Novel 4-substituted-2(1H)-phthalazinone derivatives: synthesis, molecular
      modeling study and their effects on alpha-receptors.
AB  - Novel 4-(4-bromophenyl)phthalazine derivatives connected via an alkyl spacer to
      amine or N-substituted piperazine were designed and synthesized as promising
      alpha-adrenoceptor antagonists. The structures of the phthalazine derivatives
      were established using elemental and spectral analyses. Twelve of the tested
      compounds displayed significant alpha-blocking activity. Molecular modeling
      studies were performed to rationalize the biological results. Among the tested
      compounds, 7j displayed the best-fitting score and the highest in vitro activity.

PMID- 23543654
TI  - Renoprotective effect of aged garlic extract in streptozotocin-induced diabetic
      rats.
AB  - OBJECTIVE: Aged garlic extract (AGE) has been proven to exhibit antioxidant,
      hypolipidemic, hypoglycemic and antidiabetic properties. However, its effect on
      diabetic nephropathy was unexplored. Therefore, the present study was designed to
      investigate the renoprotective effect of AGE in streptozotocin-induced diabetic
      rats. MATERIALS AND METHODS: Albino Wistar rats were induced with diabetes by a
      single intraperitoneal injection of 45 mg/kg b.w. of streptozotocin. Commercially
      available AGE was supplemented orally at a dose of 500 mg/kg body weight/day.
      Aminoguanidine, which has been proven to be an anti-glycation agent was used as
      positive control and was supplemented at a dose of 1 g/L in drinking water. The
      serum and urinary biochemical parameters were analyzed in all the groups and at
      the end of 12 weeks follow up, the renal histological examination were performed
      using H & E and PAS staining. RESULTS: The diabetic rats showed a significant
      change in the urine (P < 0.001) and serum (P < 0.01) constituents such as
      albumin, creatinine, urea nitrogen and glycated hemoglobin. In addition, the
      serum lipid profile of the diabetic rats were altered significantly (P < 0.05)
      compared to that of the control rats. However, the diabetic rats supplemented
      with aged garlic extract restored all these biochemical changes. The efficacy of
      the extract was substantiated by the histopathological changes in the kidney.
      CONCLUSION: From our results, we conclude that aged garlic extract has the
      ability to ameliorate kidney damage in diabetic rats and the renoprotective
      effect of AGE may be attributed to its anti-glycation and hypolipidemic
      activities.

PMID- 23543655
TI  - NR5A1 (SF-1) mutations are not a major cause of primary ovarian insufficiency.
AB  - CONTEXT: Primary ovarian insufficiency (POI) is a disorder affecting
      approximately 1% of women under the age of 40 years. NR5A1 (SF-1) mutations have
      been recently reported in association with POI. OBJECTIVE: Our objective was to
      evaluate the frequency and functional impact of NR5A1 variants in POI. PATIENTS
      AND METHODS: One hundred eighty patients diagnosed with idiopathic POI were
      screened for NR5A1 mutations and functional analysis was performed for the
      identified variants. The DNA-binding capacity of the variants was evaluated by
      means of EMSA, while their transcriptional activity was assessed using luciferase
      reporter assays. RESULTS: Sequencing the NR5A1 gene revealed 4 missense variants
      in 3 patients. These patients were aged 20, 25, and 33 years at diagnosis and
      presented with secondary amenorrhea. None of them presented a syndromic form,
      although 2 had a familial history of POI. The functional analysis carried out for
      these missense variants showed no significant difference in DNA binding capacity
      or in transcriptional activity compared to wild-type NR5A1. CONCLUSIONS: Our
      study in a large cohort of patients with POI showed the prevalence of NR5A1
      mutations to be low (1.6%, upper 95% confidence interval 3.5%). Moreover, no
      functional impact was observed. Overall, in contrast with the initial report, our
      results exclude NR5A1 mutations as a major genetic cause of POI.

PMID- 23543656
TI  - Variations in the size of the major omentum are primarily determined by fat cell
      number.
AB  - OBJECTIVE: Accumulation of visceral adipose tissue (VAT) is strongly linked to
      insulin resistance. Variations in the size of any adipose depot are determined by
      alterations in adipocyte volume and/or number. The individual contribution of
      each of the latter factors was determined in the major omentum, a fully
      resectable VAT depot. SUBJECTS: Total removal of the major omentum (omentectomy)
      was performed in conjunction with bariatric surgery in 55 obese patients. Tissue
      weight as well as mean adipocyte size and number in the omentum were determined.
      In subgroups, total VAT was estimated by computerized tomography (n = 17) or dual
      energy x-ray absorptiometry (n = 34). RESULTS: The weight of the major omentum
      (on average 0.6 kg) correlated significantly with total VAT mass estimated by
      computerized tomography or dual-energy x-ray absorptiometry (r = 0.48-0.7; P <
      .01). Omental weight in relation to total body fat correlated with several
      features of the metabolic syndrome and inversely with serum-leptin (P < .001).
      Mean adipocyte size and total adipocyte number correlated strongly with omental
      weight (r = 0.6-0.8; P < .0001), irrespective of body mass index and total body
      fat mass, and accounted almost in total for interindividual variations in omental
      size. However, stepwise regression analysis demonstrated that adipocyte number
      was significantly (P < .0001) more important (62%) than adipocyte size (35%).
      CONCLUSION: The size of the major omentum is representative for VAT mass and
      correlates with a pernicious metabolic profile. Variations in omental weight are
      primarily determined by adipocyte number and to a lesser degree by adipocyte
      size, suggesting that increased VAT mass in obesity is predominantly dependent on
      adipocyte proliferation.

PMID- 23543657
TI  - Effects of transoral gastroplasty on glucose homeostasis in obese subjects.
AB  - CONTEXT AND OBJECTIVE: Transoral gastroplasty (TOGA) is a safe and less invasive
      procedure than traditional bariatric surgery. We studied the effects of TOGA on
      the risk of progression from prediabetes to overt type 2 diabetes mellitus (T2DM)
      or on regression from diabetes or prediabetes to a lower risk category. DESIGN
      AND SETTING: Prospective, observational study (October 2008 to October 2010)
      performed at Catholic University, Rome, Italy. Fifty consecutive subjects 18-60
      years old, 35 >= body mass index < 55 kg/m2, were enrolled. Glucose tolerance,
      insulin sensitivity, and secretion were studied at baseline and 1 week and 1, 6,
      and 12 months after TOGA. Plasma glucagon-like peptide-1 (GLP-1), glucose
      dependent insulinotropic peptide (GIP), and ghrelin levels were measured.
      RESULTS: Forty-three patients (86%) completed the 1-year postoperative follow-up.
      Patients lost 16.90% of baseline weight (P level * factor time <0.001). Body mass
      index decreased from 42.24 +/- 3.43 to 34.65 +/- 4.58 kg/m2 (P < .001). Twenty
      three patients (53.5%) were diagnosed as normal glucose tolerance (NGT) before
      treatment, 2 (4.6%) were impaired fasting glucose (IFG), 12 (27.9%) were impaired
      glucose tolerance (IGT), 1 (2.3%) had both IFG and IGT, and 5 (11.6%) had T2DM.
      At 1-year posttreatment, the percentages changed to 86.0% NGT, 2.3% IFG, 11.6%
      IGT, 0% IFG plus IGT, and 0% T2DM, respectively. Peripheral insulin resistance
      and homeostasis model of assessment-insulin resistance improved significantly.
      Fasting glucose-dependent insulinotropic peptide and ghrelin decreased from 316.9
      +/- 143.1 to 156.2 +/- 68.2 pg/mL (P < .001) and from 630.6 +/- 52.1 to 456.7 +/-
      73.1 pg/mL (P < .001), respectively, whereas GLP-1 increased from 16.2 +/- 4.9 to
      23.7 +/- 9.5 pg/mL (P < .001). CONCLUSIONS: TOGA induced glucose disposal
      improvement with regression of diabetes to NGT or IGT and regression of IGT and
      IFG to NGT in half of the cases. Regressors showed a much larger increase of GLP
      1 levels than progressors.

PMID- 23543658
TI  - Drug prescription patterns in patients with Addison's disease: a Swedish
      population-based cohort study.
AB  - CONTEXT: There are no published data on drug prescription in patients with
      Addison's disease (AD). OBJECTIVE: Our objective was to describe the drug
      prescription patterns in Swedish AD patients before and after diagnosis compared
      with population controls. DESIGN AND SETTING: We conducted a population-based
      cohort study in Sweden. PATIENTS: Through the Swedish National Patient Register
      and the Swedish Prescribed Drug Register, we identified 1305 patients with both a
      diagnosis of AD and on combination treatment with hydrocortisone/cortisone
      acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient
      charts was not available. We identified 11 996 matched controls by the Register
      of Population. MAIN OUTCOME MEASURE: We determined the ratio of observed to
      expected number of patients treated with prescribed drugs. RESULTS: Overall,
      Swedish AD patients received more prescribed drugs than controls, and 59.3% of
      the AD patients had medications indicating concomitant autoimmune disease.
      Interestingly, both before and after the diagnosis of AD, patients used more
      gastrointestinal medications, antianemic preparations, lipid-modifying agents,
      antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive
      airway disease (all P values < .05). Notably, an increased prescription of
      several antihypertensive drugs and high-ceiling diuretics was observed after the
      diagnosis of AD. CONCLUSION: Gastrointestinal symptoms and anemia, especially in
      conjunction with autoimmune disorders, should alert the physician about the
      possibility of AD. The higher use of drugs for cardiovascular disorders after
      diagnosis in patients with AD raises concerns about the replacement therapy.

PMID- 23543659
TI  - Relationships between serum adiponectin and bone density, adiposity and calcified
      atherosclerotic plaque in the African American-Diabetes Heart Study.
AB  - CONTEXT: Adiposity, bone mineral density (BMD), and calcified atherosclerotic
      plaque (CP) exhibit complex interrelationships that are not well understood.
      Adipokines vary in relation to changes in body composition and may play roles in
      regulation of BMD and risk of cardiovascular disease. OBJECTIVE: Our objective
      was to examine the relationship between serum adiponectin and quantitative
      computed tomography-derived measures of volumetric BMD (vBMD) in thoracic and
      lumbar vertebrae, adipose tissue volumes, and CP in coronary, carotid, and
      infrarenal aortoiliac arteries. Generalized linear models were fitted to test for
      associations between adiponectin and measured phenotypes. PARTICIPANTS: A total
      of 479 unrelated African Americans with type 2 diabetes, 57% female with a mean
      +/- SD (median) age of 55.6 +/- 9.5 (55.0) years and diabetes duration of 10.3 +/
      8.2 (8.0) years. RESULTS: Serum adiponectin was 8.26 +/- 7.41 (6.10) MUg/mL,
      coronary artery CP mass score was 280 +/- 634 (14), carotid artery CP was 47 +/-
      133 (0), and aortoiliac CP was 1616 +/- 2864 (319). Women had significantly
      higher body mass index and serum adiponectin and lower coronary and carotid
      artery calcium than males (all P < .05). Before and after adjusting for age, sex,
      body mass index, mean arterial pressure, smoking status, hemoglobin A1c,
      thiazolidinedione use, and low-density lipoprotein-cholesterol, adiponectin was
      inversely associated with thoracic and lumbar vertebral vBMD [parameter estimates
      (PEs) of -0.06 and -0.021, respectively; both P < .0005], visceral adipose tissue
      (PE -0.02; P < 0.0001), and C-reactive protein (PE -0.07; P < .0001) and
      positively associated with intermuscular adipose tissue (PE 0.01; P = .03). After
      covariate adjustment, significant associations were not observed between
      adiponectin and CP in any vascular bed (P > .1). CONCLUSION: Serum adiponectin
      levels were inversely associated with cross-sectional measures of thoracic and
      lumbar vertebral vBMD, inflammation, and visceral adiposity in African Americans
      but not with vascular CP after adjustment for covariates. The data support a
      regulatory/signaling role for adiponectin in the modulation of bone density.

PMID- 23543661
TI  - Direct effects of locally administered lipopolysaccharide on glucose, lipid, and
      protein metabolism in the placebo-controlled, bilaterally infused human leg.
AB  - CONTEXT: Accumulating evidence suggests that chronic exposure to
      lipopolysaccharide (LPS, endotoxin) may create a constant low-grade inflammation,
      leading to insulin resistance and diabetes. All previous human studies assessing
      the metabolic actions of LPS have used systemic administration, making
      discrimination between direct and indirect effects impossible. OBJECTIVE: We
      sought to define the direct, placebo-controlled effects of LPS on insulin
      resistance and protein and lipid metabolism in the infused human leg without
      systemic interference from cytokines and stress hormones. DESIGN: This was a
      randomized, placebo-controlled, single-blinded study. PARTICIPANTS AND
      INTERVENTION: We studied 8 healthy volunteers with bilateral femoral vein and
      artery catheters during a 3-hour basal and 3-hour hyperinsulinemic-euglycemic
      clamp period with bilateral muscle biopsies in each period during infusion with
      saline and LPS. RESULTS: Overall, LPS perfusion significantly decreased leg
      glucose uptake, and during the clamp LPS decreased glucose arteriovenous
      differences (0.65 +/- 0.07 mmol/L vs 0.73 +/- 0.08 mmol/L). Net palmitate release
      was increased by LPS, and secondary post hoc testing indicated increased
      palmitate isotopic dilution, although primary ANOVA tests did not reveal
      significant dilution. Leg blood flows, phenylalanine, lactate kinetics,
      cytokines, and intramyocellular insulin signaling were not affected by LPS. LPS
      thus directly inhibits insulin-stimulated glucose uptake and increases palmitate
      release in the perfused human leg without detectable effects on amino acid
      metabolism. CONCLUSIONS: These data strongly suggest that the primary metabolic
      effect of LPS is increased lipolysis and muscle insulin resistance, which,
      together with secondary insulin resistance, caused by systemic cytokine and
      stress hormone release may lead to overt glucose intolerance and diabetes.

PMID- 23543660
TI  - Teriparatide for idiopathic osteoporosis in premenopausal women: a pilot study.
AB  - CONTEXT: Premenopausal women with idiopathic osteoporosis (IOP) have abnormal
      cortical and trabecular bone microarchitecture. OBJECTIVE: The purpose of this
      study was to test the hypotheses that teriparatide increases bone mineral density
      (BMD) and bone formation and improves trabecular microarchitecture and stiffness
      in women with IOP. DESIGN: This was an open-label pilot study. SETTING: The
      setting was a tertiary care referral center. PATIENTS: Participants were 21
      premenopausal women with unexplained fragility fractures or low BMD.
      INTERVENTION: Teriparatide was administered at 20 MUg daily for 18 to 24 months.
      MAIN OUTCOME MEASURES: The primary endpoint was within-subject percent change in
      lumbar spine BMD. Secondary endpoints included percent change in hip and forearm
      BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture,
      stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1
      (P1NP), and C-telopeptide. RESULTS: BMD increased at the spine (10.8 +/- 8.3%
      [SD]), total hip (6.2 +/- 5.6%), and femoral neck (7.6 +/- 3.4%) (all P < .001).
      Serum P1NP doubled by 1 month, peaked at 6 months, and returned to baseline by 18
      to 24 months. Transiliac biopsies demonstrated significant increases in cortical
      width and porosity and trabecular bone volume and number increased, mirrored by a
      71% increase in trabecular bone stiffness (P < .02-.001). Adipocyte area,
      perimeter, and volume/marrow volume decreased, with no change in adipocyte
      number. Four women had no increase in BMD and a blunted, delayed increase in
      serum P1NP. Nonresponders had markedly lower baseline bone formation rate (0.002
      +/- 0.001 vs 0.011 +/- 0.006 mm2/mm/y; P < .001) and higher serum IGF-1 (208 +/-
      54 vs 157+/- 44 ng/mL; P = .03). CONCLUSIONS: Teriparatide was associated with
      increased spine and hip BMD and improved trabecular microarchitecture and
      stiffness at the iliac crest in the majority of women with IOP.

PMID- 23543662
TI  - Comparison of mortality in hyperthyroidism during periods of treatment with
      thionamides and after radioiodine.
AB  - CONTEXT: Hyperthyroidism is common, but opinions regarding optimal therapy with
      antithyroid drugs or radioiodine (131-I) differ. There are no randomized trials
      comparing these options in terms of mortality. OBJECTIVE: The aim of the study
      was to determine whether mortality associated with hyperthyroidism varies with
      treatment administered or other factors. DESIGN, SETTING, AND PATIENTS: We
      conducted a prospective observational population-based study of 1036 subjects
      aged >= 40 years presenting to a single specialist clinic from 1989-2003 with a
      first episode of hyperthyroidism who were followed until June 2012.
      INTERVENTIONS: Antithyroid drugs or radioiodine (131-I) were administered. MAIN
      OUTCOME MEASURES: We compared causes of death with age-, sex-, and period
      specific mortality in England and Wales and used within-cohort analysis of
      influence of treatment modality, outcome, disease etiology, severity and control,
      and comorbidities. RESULTS: In 12 868 person-years of follow-up, 334 died vs
      290.6 expected (standardized mortality ratio [SMR], 1.15 [95% confidence interval
      (CI),1.03-1.28]; P = .01). Increased all-cause mortality largely reflected
      increased circulatory deaths (SMR, 1.20 [95% CI, 1.01-1.43]; P = .04). All-cause
      mortality was increased for the person-years accumulated during thionamide
      treatment (SMR, 1.30 [95% CI, 1.05-1.61]; P = .02) and after 131-I not associated
      with hypothyroidism (SMR, 1.24 [95% CI, 1.04-1.46]; P = .01) but not during T4
      replacement for 131-I-induced hypothyroidism (SMR, 0.98 [95% CI, 0.82-1.18]; P =
      .85). Within-cohort analysis comparing mortality during thionamide treatment
      showed a similar hazard ratio (HR) for all-cause mortality when 131-I did not
      result in hypothyroidism (HR, 0.95 [95% CI, 0.70-1.29]), but reduced mortality
      with 131-I-induced hypothyroidism (HR, 0.70 [95% CI, 0.51-0.96]). Reduced
      mortality associated with hypothyroidism was seen only in those without
      significant comorbidities and not in those with other serious diseases. Atrial
      fibrillation at presentation (P = .02) and an increment of 10 pmol/L in serial
      free T4 concentration during follow-up (P = .009) were independently associated
      with mortality. CONCLUSIONS: Among hyperthyroid subjects aged 40 years or older,
      mortality was increased during periods of thionamide treatment and after
      radioiodine not resulting in hypothyroidism, but not during follow-up after
      radioiodine-induced hypothyroidism. Independent associations of mortality with
      atrial fibrillation and incomplete biochemical control during treatment indicate
      potential causative links with poor outcome.

PMID- 23543663
TI  - Assessment of OPG/RANK/RANKL gene expression levels in peripheral blood
      mononuclear cells (PBMC) after treatment with strontium ranelate and ibandronate
      in patients with postmenopausal osteoporosis.
AB  - CONTEXT: Recent research results have confirmed the high significance of the
      OPG/RANK/RANKL system in the development of bone diseases. AIM: The aim of the
      reported study was to assess gene expression levels of the OPG/RANK/RANKL system
      in peripheral blood mononuclear cells (PBMCs) after strontium ranelate (SR) and
      ibandronate administered to patients with postmenopausal osteoporosis. PATIENTS
      AND METHODS: A total of 89 postmenopausal women, aged 51 to 85 years, patients of
      the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz,
      were enrolled into the study. The patients were randomly assigned to different
      medical therapies: ibandronate and SR. Patients of the control group received
      only calcium and vitamin D3 supplements. Patient visits were repeated after 3 and
      6 months. Measurements of serum alkaline phosphatase concentrations and of RNA
      expression in PBMCs as well as of total serum calcium and phosphate levels and of
      their 24-hour urine excretion rates were carried out in material, collected at
      baseline and after 3 and 6 months of the therapy. Densitometry of the left hip
      and of the lumbar spine was done at the baseline visit and after 6 months.
      RESULTS: The differences in gene expressions of RANKL and RANK were not
      significant during the study period and did not differ between the groups in a
      statistically significant manner. No OPG gene expression was observed in PBMCs of
      patients in any of the studied groups and at any time point. The tendency of
      correlation (P = .07) was observed between decreasing RANK gene expression and
      increasing bone mineral density in the patients treated with SR. CONCLUSIONS:
      Both ibandronate and SR do not seem to cause any significant changes in gene
      expression levels of OPG/RANK/RANKL in PBMCs during the first 6 months of
      treatment.

PMID- 23543665
TI  - Up-regulation of miR-146b and down-regulation of miR-200b contribute to the
      cytotoxic effect of histone deacetylase inhibitors on ras-transformed thyroid
      cells.
AB  - CONTEXT: Histone deacetylase inhibitors (HDACis) are anticancer agents that
      inhibit tumor cell growth and/or survival. However, their mechanism of action
      remains largely undefined. Recently, we have demonstrated that HDACis induce
      apoptosis in a model of rat thyroid cells transformed by the v-ras-Ki oncogene
      (FRTL-5 v-ras-Ki). The stabilization of TNF-related apoptosis-inducing ligand
      (TRAIL) protein, due to its reduced ubiquitination and proteasome degradation,
      accounts for the apoptotic effect induced specifically by suberoylanilide
      hydroxamic acid (SAHA, Vorinostat) in the v-ras-Ki thyroid transformed cells.
      OBJECTIVE: The aim of this work was to investigate whether SAHA may induce its
      cytotoxic effects also deregulating microRNA (miRNA) expression levels. DESIGN:
      We analyzed the miRNA expression profile of the thyroid transformed cells, FRTL-5
      v-ras-Ki, upon SAHA treatment. RESULTS: Here we report that SAHA induces the down
      regulation of 18 and the up-regulation of 11 miRNAs with a fold change higher
      than 2 in the transformed cells. Then, we focus on the miR-146b and miR-200b,
      respectively up-regulated and down-regulated by SAHA. We show that both these
      miRNAs target genes coding for proteins with a critical role in proteasome
      composition and ubiquitin degradation. CONCLUSION: These results suggest a role
      of miRNA deregulation in TRAIL protein stabilization responsible for SAHA-induced
      apoptotic effect in thyroid transformed cells.

PMID- 23543666
TI  - Body composition variation and impact of low skeletal muscle mass in patients
      with advanced medullary thyroid carcinoma treated with vandetanib: results from a
      placebo-controlled study.
AB  - OBJECTIVES: Vandetanib was approved by the U.S. Food and Drug Association for the
      treatment of advanced medullary thyroid cancer (MTC). Because body weight (BW)
      loss is observed in MTC and because low skeletal muscle mass (SM) is associated
      with drug toxicity, this study assessed effects of vandetanib on SM and adipose
      tissue (AT) and explored the association between SM, toxicity, and serum
      concentration of vandetanib. METHODS: Thirty-three patients with MTC received
      vandetanib (n = 23) or placebo (n = 10) in the ZETA study. Visceral AT (VAT), sc
      AT (SAT), and SM were assessed with computed tomography imaging by measuring
      tissue cross-sectional areas (square centimers per square meter). Dose-limiting
      toxicities (DLTs) were prospectively recorded. RESULTS: Early at 3 months,
      compared with placebo group who lost BW, muscle, and SAT, patients treated with
      vandetanib gained 1.5 kg BW (P = 0.02), 1.3 cm(2)/m(2) (~0.7 kg) of SM (P =
      0.009), and 4.5 cm(2)/m(2) (~0.5 kg) of SAT (P = 0.004) and gained more VAT, 5.1
      cm(2)/m(2) (~0.7 kg) (P = 0.02). Patients with DLT had lower SM index (37.2 vs
      44.3 cm(2)/m(2), P = 0.003) and a higher vandetanib serum concentration (1091 vs
      739 ng/mL, P = 0.03). Patients with SM index <43.1 cm(2)/m(2) had a higher
      probability of DLT (73% vs 14%, P = 0.004) and a higher vandetanib serum
      concentration (1037 vs 745 ng/mL, P = 0.04). Patients with the highest compared
      with the intermediate and lower levels of vandetanib serum concentration
      experienced more DLT, respectively, 78% vs 40% vs 20% (P = 0.04). CONCLUSIONS:
      Muscle and adipose tissues are restored after only 3 months of vandetanib
      treatment. Patients with low muscle mass had high vandetanib serum concentration
      and high incidence of toxicities.

PMID- 23543664
TI  - GrowthHormone Research Society workshop summary: consensus guidelines for
      recombinant human growth hormone therapy in Prader-Willi syndrome.
AB  - CONTEXT: Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has
      been used by the medical community and advocated by parental support groups since
      its approval in the United States in 2000 and in Europe in 2001. Its use in PWS
      represents a unique therapeutic challenge that includes treating individuals with
      cognitive disability, varied therapeutic goals that are not focused exclusively
      on increased height, and concerns about potential life-threatening adverse
      events. OBJECTIVE: The aim of the study was to formulate recommendations for the
      use of rhGH in children and adult patients with PWS. EVIDENCE: We performed a
      systematic review of the clinical evidence in the pediatric population, including
      randomized controlled trials, comparative observational studies, and long-term
      studies (>3.5 y). Adult studies included randomized controlled trials of rhGH
      treatment for >= 6 months and uncontrolled trials. Safety data were obtained from
      case reports, clinical trials, and pharmaceutical registries. METHODOLOGY: Forty
      three international experts and stakeholders followed clinical practice guideline
      development recommendations outlined by the AGREE Collaboration
      (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive
      multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). CONCLUSIONS: Following
      a multidisciplinary evaluation, preferably by experts, rhGH treatment should be
      considered for patients with genetically confirmed PWS in conjunction with
      dietary, environmental, and lifestyle interventions. Cognitive impairment should
      not be a barrier to treatment, and informed consent/assent should include
      benefit/risk information. Exclusion criteria should include severe obesity,
      uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active
      cancer, or psychosis. Clinical outcome priorities should vary depending upon age
      and the presence of physical, mental, and social disability, and treatment should
      be continued for as long as demonstrated benefits outweigh the risks.

PMID- 23543668
TI  - Vasohibin-1 is a new predictor of disease-free survival in operated patients with
      renal cell carcinoma.
AB  - BACKGROUND: Vasohibin-1 (VASH1) is an endothelium-produced angiogenesis
      inhibitor. Renal cell carcinoma is highly vascularised, but the significance of
      endogenous VASH1 in renal cell carcinoma has not been defined. AIMS: To identify
      VASH1 expression and its possible relationship with various clinicopathological
      factors and prognosis in renal cell carcinoma. METHODS: A retrospective analysis
      of 122 tumours obtained from 118 consecutive patients with renal cell carcinoma
      was performed. The expression patterns of VASH1, CD31, vascular endothelial
      growth factor (VEGF) and VEGF receptor type 2 (VEGFR2) were examined
      immunohistochemically and their relationships with clinicopathological factors
      were analysed. RESULTS: Microvessel density, VASH1 and VEGFR2 expression were
      significantly higher in clear cell carcinoma than in other subtypes. The VEGF
      expression pattern differed significantly between clear cell carcinoma and other
      histological subtypes. VASH1, pT factor and TNM stage were significantly
      associated with disease-free survival (p=0.030, p = 0.0012 and p = 0.0018,
      respectively). Cox models of multivariable disease-free survival analyses
      indicated that VASH1 and stage are independent prognostic factors (p=0.019 and p
      = 0.024). CONCLUSIONS: VASH1 expression may be useful for estimating the
      prognosis of renal cell carcinoma. Further studies of the role of VASH1 in renal
      cell carcinoma involving larger sample sizes are warranted.

PMID- 23543667
TI  - Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid
      malignancy.
AB  - CONTEXT: Hurthle cell cancer (HCC) is an understudied cancer with poor prognosis.
      OBJECTIVE: Our objective was to elucidate the genomic foundations of HCC. DESIGN
      AND SETTING: We conducted a large-scale integrated analysis of mutations, gene
      expression profiles, and copy number alterations in HCC at a single tertiary-care
      cancer institution. METHODS: Mass spectrometry-based genotyping was used to
      interrogate hot spot point mutations in the most common thyroid oncogenes: BRAF,
      RET, NRAS, HRAS, KRAS, PIK3CA, MAP2K1, and AKT1. In addition, common oncogenic
      fusions of RET and NTRK1 as well as PAX8/PPARgamma and AKAP9-BRAF were also
      assessed by RT-PCR. Global copy number changes and gene expression profiles were
      determined in the same tumor set as the mutational analyses. RESULTS: We report
      that the mutational, transcriptional, and copy number profiles of HCC were
      distinct from those of papillary thyroid cancer and follicular thyroid cancer,
      indicating HCC to be a unique type of thyroid malignancy. Unsupervised
      hierarchical clustering of gene expression showed the 3 groups of Hurthle tumors
      (Hurthle cell adenoma [HA], minimally invasive Hurthle cell carcinoma [HMIN], and
      widely invasive Hurthle cell carcinoma [HWIDE] clustered separately with a marked
      difference between HWIDE and HA. Global copy number analysis also indicated
      distinct subgroups of tumors that may arise as HWIDE and HMIN. Molecular pathways
      that differentiate HA from HWIDE included the PIK3CA-Akt-mTOR and Wnt/beta
      catenin pathways, potentially providing a rationale for new targets for this type
      of malignancy. CONCLUSIONS: Our data provide evidence that HCC may be a unique
      thyroid cancer distinct from papillary and follicular thyroid cancer.

PMID- 23543669
TI  - Neonatal meningoventriculitis due to proteus mirabilis - a case report.
AB  - A five day old full term born baby was admitted to our Neonatal Intensive Care
      Unit with seizures, opisthotonous posture and was icteric upto thigh. Baby had a
      three day history of poor feeding, lethargy and abnormal body movements. Mother
      was a 29 years old primigravida and had a normal vaginal delivery at home. Sepsis
      profile of the patient was requested, lumbar puncture and ventricular tap was
      performed. Patient was put on third generation cephalosporins, aminoglycosides
      and phenobarbitone. Culture and sensitivity report of blood, Cerebro spinal fluid
      and ventricular fluid showed Proteus mirabilis. Computerized Tomography scan
      showed a large parenchymal lesion in the right frontal lobe and diffuse ependymal
      enhancement along both the lateral ventricles suggestive of meningoventriculitis.
      We hereby present a fatal case of neonatal meningoventriculitis due to Proteus
      mirabilis.

PMID- 23543670
TI  - Detection and characterization of megasatellites in orthologous and
      nonorthologous genes of 21 fungal genomes.
AB  - Megasatellites are large DNA tandem repeats, originally described in Candida
      glabrata, in protein-coding genes. Most of the genes in which megasatellites are
      found are of unknown function. In this work, we extended the search for
      megasatellites to 20 additional completely sequenced fungal genomes and extracted
      216 megasatellites in 203 out of 142,121 genes, corresponding to the most
      exhaustive description of such genetic elements available today. We show that
      half of the megasatellites detected encode threonine-rich peptides predicted to
      be intrinsically disordered, suggesting that they may interact with several
      partners or serve as flexible linkers. Megasatellite motifs were clustered into
      several families. Their distribution in fungal genes shows that different motifs
      are found in orthologous genes and similar motifs are found in unrelated genes,
      suggesting that megasatellite formation or spreading does not necessarily track
      the evolution of their host genes. Altogether, these results suggest that
      megasatellites are created and lost during evolution of fungal genomes, probably
      sharing similar functions, although their primary sequences are not necessarily
      conserved.

PMID- 23543671
TI  - Central carbon metabolism and electron transport in Chlamydomonas reinhardtii:
      metabolic constraints for carbon partitioning between oil and starch.
AB  - The metabolism of microalgae is so flexible that it is not an easy task to give a
      comprehensive description of the interplay between the various metabolic
      pathways. There are, however, constraints that govern central carbon metabolism
      in Chlamydomonas reinhardtii that are revealed by the compartmentalization and
      regulation of the pathways and their relation to key cellular processes such as
      cell motility, division, carbon uptake and partitioning, external and internal
      rhythms, and nutrient stress. Both photosynthetic and mitochondrial electron
      transfer provide energy for metabolic processes and how energy transfer impacts
      metabolism and vice versa is a means of exploring the regulation and function of
      these pathways. A key example is the specific chloroplast localization of
      glycolysis/gluconeogenesis and how it impacts the redox poise and ATP budget of
      the plastid in the dark. To compare starch and lipids as carbon reserves, their
      value can be calculated in terms of NAD(P)H and ATP. As microalgae are now
      considered a potential renewable feedstock, we examine current work on the
      subject and also explore the possibility of rerouting metabolism toward lipid
      production.

PMID- 23543672
TI  - An expanded genetic code in Candida albicans to study protein-protein
      interactions in vivo.
AB  - For novel insights into the pathogenicity of Candida albicans, studies on
      molecular interactions of central virulence factors are crucial. Since methods
      for the analysis of direct molecular interactions of proteins in vivo are scarce,
      we expanded the genetic code of C. albicans with the synthetic photo-cross
      linking amino acid p-azido-L-phenylalanine (AzF). Interacting molecules in close
      proximity of this unnatural amino acid can be covalently linked by UV-induced
      photo-cross-link, which makes unknown interacting molecules available for
      downstream identification. Therefore, we applied an aminoacyl-tRNA synthetase and
      a suppressor tRNA pair (EcTyrtRNA(CUA)) derived from Escherichia coli, which was
      previously reported to be orthogonal in Saccharomyces cerevisiae. We further
      optimized the aminoacyl-tRNA synthetase for AzF (AzF-RS) and EcTyrtRNA(CUA) for
      C. albicans and identified one AzF-RS with highest charging efficiency.
      Accordingly, incorporation of AzF into selected model proteins such as Tsa1p or
      Tup1p could be considerably enhanced. Immunologic detection of C-terminally
      tagged Tsa1p and Tup1p upon UV irradiation in a strain background containing
      suppressor tRNA and optimized AzF-RS revealed not only the mutant monomeric forms
      of these proteins but also higher-molecular-weight complexes, strictly depending
      on the specific position of incorporated AzF and UV excitation. By Western
      blotting and tandem mass spectrometry, we could identify these higher-molecular
      weight complexes as homodimers consisting of one mutant monomer and a differently
      tagged, wild-type version of Tsa1p or Tup1p, respectively, demonstrating that
      expanding the genetic code of C. albicans with the unnatural photo-cross-linker
      amino acid AzF and applying it for in vivo binary protein interaction analyses is
      feasible.

PMID- 23543673
TI  - Diverse Hap43-independent functions of the Candida albicans CCAAT-binding
      complex.
AB  - The CCAAT motif is ubiquitous in promoters of eukaryotic genomes. The CCAAT
      binding complex (CBC) is conserved across a wide range of organisms, specifically
      recognizes the CCAAT motif, and modulates transcription directly or in
      cooperation with other transcription factors. In Candida albicans, CBC is known
      to interact with the repressor Hap43 to negatively regulate iron utilization
      genes in response to iron deprivation. However, the extent of additional
      functions of CBC is unclear. In this study, we explored new roles of CBC in C.
      albicans and found that CBC pleiotropically regulates many virulence traits in
      vitro, including negative control of genes responsible for ribosome biogenesis
      and translation and positive regulation of low-nitrogen-induced filamentation. In
      addition, C. albicans CBC is involved in utilization of host proteins as nitrogen
      sources and in repression of cellular flocculation and adhesin gene expression.
      Moreover, our epistasis analyses suggest that CBC acts as a downstream effector
      of Rhb1-TOR signaling and controls low-nitrogen-induced filamentation via the
      Mep2-Ras1-protein kinase A (PKA)/mitogen-activated protein kinase (MAPK) pathway.
      Importantly, the phenotypes identified here are all independent of Hap43.
      Finally, deletion of genes encoding CBC components slightly attenuated C.
      albicans virulence in both zebrafish and murine models of infection. Our results
      thus highlight new roles of C. albicans CBC in regulating multiple virulence
      traits in response to environmental perturbations and, finally, suggest potential
      targets for antifungal therapies as well as extending our understanding of the
      pathogenesis of other fungal pathogens.

PMID- 23543674
TI  - Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb
      in anesthetized and awake states.
AB  - The acquisition of olfactory information and its early processing in mammals are
      modulated by brain states through sniffing behavior and neural feedback. We
      imaged the spatiotemporal pattern of odor-evoked activity in a population of
      output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head
      restrained mice expressing a genetically-encoded calcium indicator. The temporal
      dynamics of MTC population activity were relatively simple in anesthetized
      animals, but were highly variable in awake animals. However, the apparently
      irregular activity in awake animals could be predicted well using sniff timing
      measured externally, or inferred through fluctuations in the global responses of
      MTC population even without explicit knowledge of sniff times. The overall
      spatial pattern of activity was conserved across states, but odor responses had a
      diffuse spatial component in anesthetized mice that was less prominent during
      wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were
      the likely source of spatially disperse responses in the anesthetized animal. Our
      data demonstrate that the temporal and spatial dynamics of MTCs can be
      significantly modulated by behavioral state, and that the ensemble activity of
      MTCs can provide information about sniff timing to downstream circuits to help
      decode odor responses.

PMID- 23543675
TI  - Zotepine-induced convulsive seizures in a chronic case of treatment resistant
      paranoid schizophrenia.
AB  - Adverse effects to antipsychotics are varied, frequently intolerable, often
      serious and sometimes fatal in clinical practice. Seizures are one of these
      adverse effects. Almost all first and second generation antipsychotics elicit
      dose-dependent lowering of seizure threshold, indicating increased seizure risk
      at higher drug dosages. The adverse event of zotepine induced seizure is
      published in few case reports. We report the occurrence of myoclonic seizure
      progressing to generalized tonic-clonic seizures with zotepine along with clear
      temporal association of dose dependent modulation evident in this case.

PMID- 23543676
TI  - The central role of comorbidity in predicting ambulatory care sensitive
      hospitalizations.
AB  - BACKGROUND: Ambulatory care sensitive hospitalizations (ACSHs) are commonly used
      as measures of access to and quality of care. They are defined as
      hospitalizations for certain acute and chronic conditions; yet, they are most
      commonly used in analyses comparing different groups without adjustment for
      individual-level comorbidity. We present an exploration of their roles in
      predicting ACSHs for acute and chronic conditions. METHODS: Using 1998-99 US
      Medicare claims for 1 06 930 SEER-Medicare control subjects and 1999 Area
      Resource File data, we modelled occurrence of acute and chronic ACSHs with
      logistic regression, examining effects of different predictors on model
      discriminatory power. RESULTS: Flags for the presence of a few comorbid
      conditions-congestive heart failure, chronic obstructive pulmonary disease,
      diabetes, hypertension and, for acute ACSHs, dementia-contributed virtually all
      of the discriminative ability for predicting ACSHs. C-statistics were up to 0.96
      for models predicting chronic ACSHs and up to 0.87 for predicting acute ACSHs. C
      statistics for models lacking comorbidity flags were lower, at best 0.73, for
      both acute and chronic ACSHs. CONCLUSION: Comorbidity is far more important in
      predicting ACSH risk than any other factor, both for acute and chronic ACSHs.
      Imputations about quality and access should not be made from analyses that do not
      control for presence of important comorbid conditions. Acute and chronic ACSHs
      differ enough that they should be modelled separately. Unaggregated models
      restricted to persons with the relevant diagnoses are most appropriate for
      chronic ACSHs.

PMID- 23543677
TI  - Influences of definition ambiguity on hospital performance indicator scores:
      examples from The Netherlands.
AB  - RESEARCH OBJECTIVE: Reliable and unambiguously defined performance indicators are
      fundamental to objective and comparable measurements of hospitals' quality of
      care. In two separate case studies (intensive care and breast cancer care), we
      investigated if differences in definition interpretation of performance
      indicators affected the indicator scores. DESIGN: Information about possible
      definition interpretations was obtained by a short telephone survey and a Web
      survey. We quantified the interpretation differences using a patient-level
      dataset from a national clinical registry (Case I) and a hospital's local
      database (Case II). In Case II, there was additional textual information
      available about the patients' status, which was reviewed to get more insight into
      the origin of the differences. PARTICIPANTS: For Case I, we investigated 15 596
      admissions of 33 intensive care units in 2009. Case II consisted of 144 admitted
      patients with a breast tumour surgically treated in one hospital in 2009.
      RESULTS: In both cases, hospitals reported different interpretations of the
      indicators, which lead to significant differences in the indicator values. Case
      II revealed that these differences could be explained by patient-related factors
      such as severe comorbidity and patients' individual preference in surgery date.
      CONCLUSIONS: With this article, we hope to increase the awareness on pitfalls
      regarding the indicator definitions and the quality of the underlying data. To
      enable objective and comparable measurements of hospitals' quality of care,
      organizations that request performance information should formalize the
      indicators they use, including standardization of all data elements of which the
      indicator is composed (procedures, diagnoses).

PMID- 23543678
TI  - Not smoking is associated with lower risk of hypertension: results of the
      Olivetti Heart Study.
AB  - BACKGROUND: Few epidemiological investigations evaluated the role of smoking
      cessation on blood pressure (BP), and the results are not univocal. Therefore,
      the aim of this study was to assess the effect of smoking cessation on the risk
      to develop hypertension (HPT) and on BP values. METHODS: This longitudinal study,
      with a follow-up period of 8 years, included the participants of the Olivetti
      Heart Study. Participants were 430 untreated normotensive non-diabetic men with
      normal renal function, examined twice in 1994-95 and in 2002-04. The sample
      included current smokers (S, n = 212), former smokers (ES, n = 145) and never
      smokers (NS, n = 73) at baseline. RESULTS: Basal body mass index (BMI), systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher
      in ES than in S (ES vs. S; BMI: 27.0 +/- 2.5 vs. 26.1 +/- 2.9 kg/m2; P < 0.01;
      SBP/DBP: 121.2 +/- 9.3/80.0 +/- 5.8 vs. 19.1 +/- 9.9/77.4 +/- 6.7 mm Hg; P <
      0.05; M +/- SD). After 8 years of follow-up, BP changes (Delta) were
      significantly lower in ES than in S (DeltaSBP/DBP: 12.6 +/- 13.4/7.9 +/- 8.1 vs.
      16.0 +/- 14.9/10.3 +/- 10.1 mm Hg; P < 0.05; M +/- SD), also after adjustment for
      potential confounders. Moreover, at the last examination, the overall HPT
      prevalence was 33%, with lower values in ES than in S (25 vs. 38%, P = 0.01).
      After accounting for age, BP and BMI at baseline, and changes in smoking habit
      over the 8-year period, ES still had significant lower risk of HPT than S (odds
      ratio 0.30, 95% confidence interval 0.15-0.58; P < 0.01). CONCLUSIONS: In this
      sample of healthy men, smoking cessation was associated with lower BP increment
      and minor HPT risk, independently of potential confounders.

PMID- 23543680
TI  - Vitiligo and autoantibodies of celiac disease.
AB  - BACKGROUND: Vitiligo is an acquired, idiopathic disorder characterized by
      circumscribed depigmented macules and patches. The exact etiology and
      pathogenesis of vitiligo is not clear. Many theories have been presented
      regarding this subject among them aautoimmune theory is the most important one.
      The association of vitiligo with other autoimmune disorders has been reported,
      but the relationship between vitiligo and celiac disease is controversial. The
      aim of this study was to study the frequency of celiac autoantibodies in a group
      of vitiligo patients compared with control. METHODS: This was a cross sectional
      case control study that involved 128 individuals, 64 vitiligo patients and 64
      individuals as control group. The means age of participants was 30.3 +/- 14.4
      years. IgA anti Endomysial antibody and IgA anti-glutaminase antibody were
      measured by ELISA method in the serum of all participants. Data were analyzed by
      SPSS software version 15. RESULTS: The serum of two vitiligo patients (3.1%) was
      positive for antibodies. All control groups were seronegative for these
      antibodies (P < 0.05). There was no significant effect of sex and job on
      seropositivity. CONCLUSION: There may be a relationship between celiac disease
      and vitiligo. This may indicate a common basic autoimmune mechanism that is an
      explanation for few case reports that gluten free diets were effective in the
      treatment of vitiligo patients. Both T test and exact fisher test showed no
      effect of age, sex and job on seropositivity of these patients (P = 0.56 and P =
      0.74, respectively).

PMID- 23543679
TI  - Manganese concentrations in maternal and umbilical cord blood: related to birth
      size and environmental factors.
AB  - BACKGROUND: Manganese (Mn) is an essential element and a potential toxicant for
      developing organism. Deficiency and excess of it were both deleterious to fetal
      growth in experimental animals. However, literature on relationship between Mn
      status and birth outcome in humans is sparse. METHODS: Mn concentrations were
      measured in mother whole blood (MWB) and umbilical cord blood (UCB) in 125 pairs
      of mother-infant; birth size was examined and relationship between them was
      analysed. Potentially environmental factors influencing Mn loads in maternal and
      fetal organisms were investigated through epidemiological method. RESULTS: Mn
      level in UCB was significantly higher than that in MWB (mean value: 54.98 vs.
      78.75 ug/L), and a significant positive correlation was shown between them. There
      was a quadratic curvilinear (inverted U-shaped curve) relationship between MWB Mn
      and birth size, and between UCB Mn and birth size. Both univariate analysis and
      multiple linear regression analysis showed that exposure to harmful occupational
      factors during gestation remarkably increased maternal and fetal Mn levels.
      Living close to major transportation routes (<500 m) also increased the MWB Mn
      levels. CONCLUSION: Our results suggested that lower or higher Mn level in
      maternal and umbilical blood may induce adverse effect on birth size in humans.
      In addition, increased levels of Mn in MWB or UCB may be associated with exposure
      to some environmental hazard factors.

PMID- 23543681
TI  - Kimura disease involving a caruncle.
AB  - A 35-year-old woman presented with history of a painless, slow-growing nodule in
      a left eye caruncle over the last 2 months. The visual acuity was 20 / 20 and the
      ocular movements were in the normal range. The venereal disease research
      laboratory test, erythrocyte sedimentation rate, serum angiotensin converting
      enzyme level, and chest radiograph were all normal. An excisional biopsy was done
      to confirm the diagnosis. A 1.3 * 0.5 * 0.3 cm sized nodule was extracted and
      sent for histopathologic examination. Hematoxylin-eosin staining showed
      follicular hyperplasia with perifollicular fibrosis, an eosinophil infiltrate,
      and proliferation of capillary vessels. The capillaries were lined by normal
      appearing, flat, spindle-shaped endothelial cells. On the basis of these
      histopathologic findings, the diagnosis of Kimura disease in a caruncle was
      established. This is the first report describing Kimura disease localized to a
      caruncle. Kimura disease should be suspected and included in the differential
      diagnosis of a caruncular mass lesion.

PMID- 23543683
TI  - Effect of vitamin e supplementation on biochemical parameters in pesticides
      sprayers of grape gardens of Western maharashtra (India).
AB  - The aim of this study was to see the biochemical effects of pesticides on
      sprayers of grape gardens before and after 15 days of vitamin E supplementations
      in Western Maharashtra (India), who were occupationally exposed to various
      pesticides over a long period of time (about 5 to 15 years). Blood samples were
      collected from all study group subjects for biochemical parameters assays before
      and after 15 days of vitamin E supplementation. Sprayers of grape gardens were
      given 400 mg of vitamin E tablet/day for 15 days. After 15 days of vitamin E
      supplementation to sprayers of grape gardens, we observed significantly decreased
      aspartate transaminase (10.88 %, P < 0.05, r = 0.88), alanine transaminase (25.92
      %, P < 0.01, r = 0.46) and total proteins (3.32 %, P < 0.01, r = 0.33), whereas,
      no statistically significant change was found in serum acetyl cholinesterase, C
      reactive proteins, albumin (ALB), globulins and ALB/globulin ratio as compared to
      before vitamin E supplementation. Sprayers of grape gardens, who received vitamin
      E supplementation, showed significantly decreased serum lipid peroxide (LP)
      (18.75 %, P < 0.001, r = 0.63) and significantly increased RBC-superoxide
      dismutase (SOD) (12.88 %, P < 0.001, r = 0.85), RBC-Catalase (CAT) (24.49 %, P <
      0.001, r = 0.70), plasma ceruloplasmin (CP) (4.6 %, P < 0.01, r = 0.80), serum
      zinc (4.57 %, P < 0.01, r = 0.83) and serum copper (4.37 %, P < 0.01, r = 0.79)
      as compared to values before vitamin E supplementation. These results showed that
      vitamin E supplementation has ameliorating effects on these transaminase enzymes,
      suggesting that it may have a protective effect on liver, from pesticides induced
      damage. In this study vitamin E supplementation might have decreased LP levels by
      breaking chain reaction of lipid peroxidation. Present results indicate that
      vitamin E plays a crucial role in restoring the antioxidant enzymes such as SOD,
      CAT and CP, in population exposed to pesticides. This helps to enhance its
      antioxidant ability. Therefore, it is suggested that farmers, pesticide
      applicators, workers in the pesticide industry and other pesticide users, who
      come in regular contact with pesticides, may be benefited by supplementation with
      vitamin E.

PMID- 23543682
TI  - Factors controlling nascent high-density lipoprotein particle heterogeneity: ATP
      binding cassette transporter A1 activity and cell lipid and apolipoprotein AI
      availability.
AB  - Nascent high-density lipoprotein (HDL) particles arise in different sizes. We
      have sought to uncover factors that control this size heterogeneity. Gel
      filtration, native PAGE, and protein cross-linking were used to analyze the size
      heterogeneity of nascent HDL produced by BHK-ABCA1, RAW 264.7, J774, and HepG2
      cells under different levels of two factors considered as a ratio, the
      availability of apolipoprotein AI (apoAI) -accessible cell lipid, and
      concentration of extracellular lipid-free apoAI. Increases in the available cell
      lipid:apoAI ratio due to either elevated ATP-binding cassette transporter A1
      (ABCA1) expression and activity or raised cell density (i.e., increasing
      numerator) shifted the production of nascent HDL from smaller particles with
      fewer apoAI molecules per particle and fewer molecules of choline-phospholipid
      and cholesterol per apoAI molecule to larger particles that contained more apoAI
      and more lipid per molecule of apoAI. A further shift to larger particles was
      observed in BHK-ABCA1 cells when the available cell lipid:apoAI ratio was raised
      still higher by decreasing the apoAI concentration (i.e., the denominator). These
      changes in nascent HDL biogenesis were reminiscent of the transition that occurs
      in the size composition of reconstituted HDL in response to an increasing initial
      lipid:apoAI molar ratio. Thus, the ratio of available cell lipid:apoAI is a
      fundamental cause of nascent HDL size heterogeneity, and rHDL formation is a good
      model of nascent HDL biogenesis.

PMID- 23543684
TI  - A sense of place.
AB  - We have to be cautious about the safety to both individual and environmental
      health of all materials that we use and advocate.

PMID- 23543685
TI  - Oral examinations.

PMID- 23543686
TI  - Authors' response.

PMID- 23543687
TI  - Creating value.

PMID- 23543688
TI  - Author's response.

PMID- 23543689
TI  - A landmark report on understanding the human dentition.

PMID- 23543690
TI  - Assessing bone's adaptive capacity around dental implants: a literature review.
AB  - BACKGROUND: Increased stress (force) on prostheses induces strain (deformation)
      in the peri-implant bone. Elevated stress and strain could result in the failure
      of implants that support prostheses. However, the survival rate of implants
      supporting prostheses under increased stress is high. Either the bone is stronger
      than expected or it adapts to increased stress. Concepts regarding bone's
      adaptive capacity continue to evolve and are the focus of this literature review.
      TYPES OF STUDIES REVIEWED: The authors searched the literature to find studies
      that addressed the bone's capacity to adjust to increased stress and strain. They
      assessed experimental and clinical trials in which investigators monitored
      healing after placement of dental implants. RESULTS: The data indicate that
      forces greater than the bone's adaptive ability can induce loss of
      osseointegration, as well as osseous resorption. In contrast, it is possible that
      increased stress on prostheses initiates a reparative process, thereby
      facilitating retention of implants experiencing increased stress. Numerous lines
      of evidence support the concept that bone can modify itself to withstand
      increased mechanical forces. PRACTICAL IMPLICATIONS: The authors provide an
      explanation for the high success rate of prostheses and implants in bone that are
      exposed to increased stress and strain.

PMID- 23543691
TI  - The association between periodontitis and coronary heart disease: a quality
      assessment of systematic reviews.
AB  - BACKGROUND: The existence of an association between periodontitis and
      cardiovascular disease has been proposed by investigators in several clinical
      studies and further confirmed by the results of several systematic reviews. The
      aim of the authors' study was to assess the quality of published systematic
      reviews focused on the association between periodontitis and coronary heart
      disease (CHD) by using established systematic review assessment checklists.
      METHODS: Two reviewers conducted a search for systematic reviews focusing on the
      association between periodontitis and CHD. Three independent reviewers appraised
      the quality of the selected 13 reviews by using an established and validated
      assessment tool for systematic reviews and another checklist. They gave each
      article a total score according to the number of criteria on each checklist that
      the article fulfilled. RESULTS: Nine reviews satisfied six or more items on the
      assessment tool, whereas two reviews each satisfied only one item. This
      assessment shows that published systematic reviews of the periodontitis-CHD
      association exhibit significant structural and methodological variation, which
      the authors further confirmed by using the second checklist. CONCLUSION:
      Systematic reviews of the association between periodontitis and CHD exhibited
      significant differences in their methodological quality. PRACTICAL IMPLICATIONS:
      Clinicians should be aware that not all systematic reviews of the periodontitis
      CHD association are conducted in a rigorous manner and should be capable of
      differentiating well-conducted reviews from poorly conducted ones.

PMID- 23543692
TI  - Breaking bad medical news in a dental care setting.
AB  - BACKGROUND: Dental care providers may diagnose diseases and conditions that
      affect a patient's general health. The authors reviewed issues related to
      breaking bad medical news to dental practice patients and provide guidance to
      clinicians about how to do so. METHODS: To help reduce the potentially negative
      effects associated with emotionally laden communication with patients about
      serious health care findings, the authors present suggestions for appropriately
      and sensitively delivering bad medical news to both patients and their families
      in a supportive fashion. RESULTS: Preparing to deliver bad news by means of
      education and practice is recommended to help prevent or reduce psychological
      distress. One form of communication guidance is the ABCDE model, which involves
      Advance preparation, Building a therapeutic relationship or environment,
      Communicating well, Dealing with patient and family reactions, and Encouraging
      and validating emotions. An alternative model is the six-step SPIKES sequence
      Setting, Perception, Invitation or Information, Knowledge, Empathy, and
      Strategize and Summarize. Using either model can assist in sensitive and
      empathetic communication. CONCLUSIONS: For both practitioners' and patients' well
      being, empathetic and effective delivery of bad medical news should be included
      in dental school curricula and continuing education courses. PRACTICAL
      IMPLICATIONS: Dental care providers should be familiar with the oral
      manifestations of diseases and the care needed before the patient undergoes
      medical treatment and use effective communication necessary to share bad news
      with patients.

PMID- 23543693
TI  - Inferior alveolar nerve block and third-molar agenesis: a retrospective clinical
      study.
AB  - BACKGROUND: Children often receive inferior alveolar nerve blocks (IANBs) when
      their third molars are just beginning to develop. The location of the third-molar
      follicle is close to where the needle penetrates during an IANB. The authors
      examined the possible association between IANBs and missing third molars.
      METHODS: The authors examined 439 potential sites of third-molar development for
      evidence of third-molar follicles on panoramic radiographs of randomly selected
      children 7 years and older. The authors conducted a statistical comparison of the
      incidence of missing third-molar follicles in a control group of children who had
      no history of receiving IANBs with children in a test group who had a definitive
      history of receiving IANBs by means of generalized estimating equations. RESULTS:
      The authors found a statistically significant greater incidence of missing third
      molar follicles in mandibular quadrants that had a definitive history of
      receiving IANBs compared with mandibular quadrants that had no history of
      receiving IANB. CONCLUSION: IANBs administered to young children when the third
      molar tooth bud is immature may stop third-molar development. Owing to the
      significant clinical implications, further research is needed to verify these
      results. PRACTICAL IMPLICATIONS: Dentists inadvertently may be stopping the
      development of third molars when administering IANBs to children.

PMID- 23543694
TI  - An assessment of the usefulness of jaw kinesiography in monitoring
      temporomandibular disorders: correlation of treatment-related kinesiographic and
      pain changes in patients receiving temporomandibular joint injections.
AB  - BACKGROUND: The authors conducted a study in patients with temporomandibular
      joint (TMJ) osteoarthritis to assess whether treatment-related changes in pain
      levels and chewing ability coincide with a change in jaw kinesiographic (KG)
      parameters. METHODS: The authors selected 34 patients with a diagnosis of TMJ
      osteoarthritis that met Research Diagnostic Criteria for Temporomandibular
      Disorders (RDC/TMD) to undergo a cycle of five weekly arthrocentesis procedures
      with injections of 1 milliliter hyaluronic acid. They performed a permutation
      test to assess the correlation between changes across time (from baseline to end
      of treatment) in two clinical outcome parameters-pain level and chewing ability
      and changes across time in the KG outcome parameters. RESULTS: The authors
      observed improvement across time in both chewing ability (F = 8.328; P = .005)
      and pain level (F = 10.903; P = .002). The authors observed no significant
      changes in any KG variables. With minor exceptions, no significant correlations
      were shown between changes in the clinical and KG parameters during the treatment
      period. CONCLUSIONS: Treatment-related changes in pain levels and chewing ability
      in patients with TMJ osteoarthritis do not coincide with changes in KG
      parameters. PRACTICAL IMPLICATIONS: If one assumes pain variables to be the
      primary outcome measures in assessing treatment of TMJ osteoarthritis, KG
      recordings of the jaw are not useful for monitoring TMJ osteoarthritis in the
      clinical setting.

PMID- 23543695
TI  - Assessing the association between bisphosphonate exposure and delayed mucosal
      healing after tooth extraction.
AB  - BACKGROUND: Tooth extraction in patients exposed to bisphosphonates (BPs) is
      considered a risk factor for osteonecrosis. The authors evaluated the time to
      mucosal healing and frequency of osteonecrosis after tooth extraction in
      participants exposed to BPs. METHODS: The authors compared wound healing after
      tooth extraction in participants exposed to BPs with that in control participants
      who had not been exposed to BPs. Variables included age, sex, type of BP therapy
      (oral or intravenous), BP exposure time and C-terminal telopeptide (CTX) test
      results. The authors followed up patients weekly or biweekly until healing was
      complete. They used multivariable analyses to model time to healing in the
      presence of covariates, and estimates provided hazard ratios (HRs) and 95 percent
      confidence intervals (CIs) adjusted for all variables in the model. RESULTS: The
      authors enrolled 53 participants with BP exposure and 39 control participants.
      Postextraction healing was significantly longer in participants exposed to BPs (P
      < .001) than it was in control participants. One patient (1.9 percent) developed
      osteonecrosis. A Cox proportional hazards model in which the authors controlled
      for age, sex and CTX values showed that BP exposure alone significantly (adjusted
      HR, 0.27; 95 percent confidence interval, 0.16-0.48) increased mucosal healing
      time [corrected]. CONCLUSIONS: The study results showed that postextraction
      healing was impaired in patients exposed to BPs. CTX values were not associated
      with delayed healing after tooth extraction. PRACTICAL IMPLICATIONS:
      Postextraction healing was delayed in patients receiving BP therapy. However, the
      risk of developing osteonecrosis was low.

PMID- 23543696
TI  - How willing are dentists to treat young children?: a survey of dentists
      affiliated with Medicaid managed care in New York City, 2010.
AB  - BACKGROUND: Despite recommendations for children to have a dental visit by the
      age of 1 year, access to dental care for young children, including children
      enrolled in Medicaid, remains limited. The authors conducted a survey to assess
      the availability of dentists to see young children enrolled in Medicaid managed
      care (MMC) in New York City (NYC), to determine barriers to the provision of
      dental care to young children and, within the context of MMC, to identify
      strategies to facilitate the delivery of dental care to children. METHODS: The
      authors mailed a survey to assess the provision of dental services to young
      children and perceived barriers and facilitators to 2,311 general dentists (GDs)
      and 140 pediatric dentists (PDs) affiliated with NYC MMC. A total of 1,127
      surveys (46 percent) were received. The authors analyzed the responses according
      to provider type, youngest aged child seen, provider's ability to see additional
      children and practice location. The authors compared responses by using the
      chi(2) test. RESULTS: Fewer than one-half (47 percent) of GDs saw children aged 0
      through 2 years. Provider type, years in practice and percentage of Medicaid
      insured patients were associated significantly (P < .005) with youngest age of
      child seen. Among respondents seeing children aged 0 through 2 years, PDs were
      significantly more likely to provide preventive therapy (P = .004) and
      restorative treatment (P < .001). Additional training and access to consulting
      PDs were identified by GDs as potential facilitators to seeing young children.
      CONCLUSION: A high proportion of NYC GDs affiliated with MMC do not see young
      children. PRACTICE IMPLICATIONS: Ninety-four percent of NYC MMC- affiliated
      dentists are GDs, but 53 percent of GD respondents did not see children aged 0
      through 2 years in their practices. Improving access to dental care for young
      children requires changes in GDs' practices, possibly by means of additional
      training and access to consulting PDs.

PMID- 23543697
TI  - Recommending the best treatment for patients.

PMID- 23543698
TI  - The ability to let go.

PMID- 23543699
TI  - What are the ethical implications of helping a colleague obtain unearned
      continuing education credit?

PMID- 23543701
TI  - Prevalence and impact of gastrointestinal helminths on body weight gain in
      backyard chickens in subtropical and humid zone of Jammu, India.
AB  - Necropsy of gastrointestinal tract of 125 free-range chickens from a subtropical
      and humid zone of northwestern India revealed four nematode spp. (Ascaridia
      galli, Heterakis gallinarum, Capillaria spp. and Cheilospirura hamulosa) and four
      cestode spp. (Raillietina cesticillus, Raillietina echinobothrida, Raillietina
      tetragona and Amoebotaenia cuneata) The overall prevalence of the helminth
      parasites was 72.0%. Amongst various helminth species encountered in the region,
      A. galli emerged out as the most prevalent, followed by H. gallinarum, R.
      cesticillus and R. echinobothrida. The impact of helminthic infections on body
      weight gain in growing chickens was investigated. One hundred growing chickens,
      aged 40 days were randomly assigned to two groups (treated and untreated
      controls) of 50 birds each. The birds in treated group were given fenbendazole at
      7.5 mg per kg body weight in drinking water, while the birds in other group
      served as untreated controls. At the end of the 90 days of the field trial, the
      mean body weight gain of untreated controls was 1232.2 +/- 7.28 g (13.7 g/day)
      compared with 1617.6 +/- 5.43 g (18.0 g/day) in the treated group. It was
      associated with a significantly (P < 0.05) higher mean worm burden (32.92 +/-
      6.12) in untreated controls than the treated group (2.46 +/- 1.14). The
      prevalences of helminthic species and their impact on body weight gain in growing
      backyard chickens have been discussed.

PMID- 23543700
TI  - Sealants and dental caries: insight into dentists' behaviors regarding
      implementation of clinical practice recommendations.
AB  - BACKGROUND: The authors conducted a qualitative study of private-practice
      dentists in their offices by using vignette-based interviews to assess barriers
      to the use of evidence-based clinical recommendations in the treatment of
      noncavitated carious lesions. METHODS: The authors recruited 22 dentists as a
      convenience sample and presented them with two patient vignettes involving
      noncavitated carious lesions. Interviewers asked participants to articulate their
      thought processes as they described treatment recommendations. Participants
      compared their treatment plans with the American Dental Association's
      recommendations for sealing noncavitated carious lesions, and they described
      barriers to implementing these recommendations in their practices. The authors
      recorded and transcribed the sessions for accuracy and themes. RESULTS: Personal
      clinical experience emerged as the determining factor in dentists' treatment
      decisions regarding noncavitated carious lesions. Additional factors were lack of
      reimbursement and mistrust of the recommendations. The authors found that
      knowledge of the recommendations did not lead to their adoption when the
      recommendation was incongruent with the dentist's personal experience.
      CONCLUSIONS: The authors found that ingrained practice behavior based on personal
      clinical experience that differed substantially from evidence-based
      recommendations resulted in a rejection of these recommendations. PRACTICAL
      IMPLICATIONS: Attempts to improve the adoption of evidence-based practice must
      involve more than simple dissemination of information to achieve a balance
      between personal clinical experience and scientific evidence.

PMID- 23543702
TI  - Therapeutic strategies, including a high surgical ligation rate, for patent
      ductus arteriosus closure in extremely premature infants in a North American
      centre.
AB  - OBJECTIVE: To document the rate of surgical ligation of a patent ductus
      arteriosus (PDA) in extremely premature infants who had received more than one
      course of indomethacin. Outcomes were compared among three subgroups (ligation,
      further indomethacin and no further treatment) of infants who received at least
      one course of indomethacin, and between two subgroups (one course of indomethacin
      and more than one course) among infants who underwent ligation. STUDY DESIGN: A
      retrospective chart review of all 23 weeks+0 days to 26 weeks+6 days' gestational
      age infants with a PDA born between 1994 and 2005 was performed. Secondary
      outcomes were compared among the subgroups. RESULTS: The final study population
      consisted of 196 extremely premature infants with a PDA. The rate of surgical
      ligation in the 88 infants who received more than one course of indomethacin was
      64%. The ligation subgroup, in comparison with the no further treatment subgroup,
      spent a greater median time on mechanical ventilation (39 versus 29 days,
      P<0.001) and in hospital (115 versus 92 days P=0.002), while trending toward
      lower mortality (18% versus 40%, P=0.07). The PDA closed following the first
      course of indomethacin in only 20% of infants. CONCLUSIONS: A majority of
      extremely premature infants receiving more than one course of indomethacin
      underwent surgical ligation. Repeated indomethacin courses were generally well
      tolerated, but were mostly unsuccessful. Ligation appears to have potential risks
      and benefits. A randomized trial should be performed after studies define a
      hemodynamically significant PDA that will result in morbidity and/or mortality
      unless treated.

PMID- 23543704
TI  - Serratia marcescens- a rare opportunistic nosocomial pathogen and measures to
      limit its spread in hospitalized patients.
AB  - BACKGROUND: In November 2011, 6 patients who were in the ICU of the Sri Guru Ram
      Dass Institute of Medical Sciences and Research acquired an infection which was
      caused by Serratia marcescens. We investigated the cause of the increase in
      frequency of the isolation of Serratia marcesens from hospitalized patients.
      METHODS: Various samples from patients and environmental sources, which were
      collected from the ICU of Sri Guru Ram Das Institute of Medical Sciences and
      Research during the 6 month period from November 2011 to April 2011, were
      included in the study. The isolates from the patients and the surrounding
      environmental sources were examined by using standard techniques. Further, the
      isolates of Serratia marcescens were identified, depending upon their biochemical
      and morphological characteristics. RESULTS: Seven isolates of Serratia marcescens
      were identified (six from the patients in the ICU and one from the soap dispenser
      in the ICU) among a total of 327 isolates from the clinical samples and 84
      isolates were identified from the environmental sources in the ICU. DISCUSSION
      AND CONCLUSION: An outbreak of the Serratia marcescens infection in the ICU was
      traced to the extrinsic contamination of the soap dispenser in the ICU, as after
      the removal of the dispenser, no further case occurred.

PMID- 23543705
TI  - Stapled haemorrhoidopexy for haemorrhoids: a review of our early experience.
AB  - Haemorrhoids is one of the most common problems seen in surgical OPD. Open
      haemorrhoidectomy has remained the gold standard for a long time with a high post
      operative morbidity. The quest for a better understanding of the pathology of
      haemorrhoids resulted in the evolvement of stapler haemorrhoidopexy. Our aim is
      to study the efficacy of stapler haemorrhoidopexy with regards to role of
      immediate post-operative morbidity. A prospective study of 50 patients (n = 50)
      with the second- and third-degree symptomatic haemorrhoids was done. The mean age
      of the patients was 44.1 years. Fourteen patients had co-morbid conditions. The
      average duration of the operation was 29 min. Patients with the second-degree
      haemorrhoids had higher rate of complication. The complication rate was 32%.
      Three patients had urinary retention. Two patients had minor bleeding, and one
      patient experienced transient discharge. The mean analgesic requirement was 2.4
      tramadol, 50 mg injections. Ten patients had significant post-operative pain.
      Average length of hospital stay was 2.7 days. There were no symptomatic
      recurrences till date.

PMID- 23543703
TI  - NMDA hypofunction as a convergence point for progression and symptoms of
      schizophrenia.
AB  - Schizophrenia is a disabling mental illness that is now recognized as a
      neurodevelopmental disorder. It is likely that genetic risk factors interact with
      environmental perturbations to affect normal brain development and that this
      altered trajectory results in a combination of positive, negative, and cognitive
      symptoms. Although the exact pathophysiology of schizophrenia is unknown, the N
      methyl-D-aspartate receptor (NMDAR), a major glutamate receptor subtype, has
      received great attention. Proper expression and regulation of NMDARs in the brain
      is critical for learning and memory processes as well as cortical plasticity and
      maturation. Evidence from both animal models and human studies implicates a
      dysfunction of NMDARs both in disease progression and symptoms of schizophrenia.
      Furthermore, mutations in many of the known genetic risk factors for
      schizophrenia suggest that NMDAR hypofunction is a convergence point for
      schizophrenia. In this review, we discuss how disrupted NMDAR function leads to
      altered neurodevelopment that may contribute to the progression and development
      of symptoms for schizophrenia, particularly cognitive deficits. We review the
      shared signaling pathways among the schizophrenia susceptibility genes DISC1,
      neuregulin1, and dysbindin, focusing on the AKT/GSK3beta pathway, and how their
      mutations and interactions can lead to NMDAR dysfunction during development.
      Additionally, we explore what open questions remain and suggest where
      schizophrenia research needs to move in order to provide mechanistic insight into
      the cause of NMDAR dysfunction, as well as generate possible new avenues for
      therapeutic intervention.

PMID- 23543706
TI  - Evidence-Based Medicine: An Obstetrician and Gynaecologist's Perspective.
AB  - OBJECTIVES: Evidence based medicine (EBM) has transformed the way healthcare is
      delivered all over the world. It combines individual clinical expertise with best
      available research evidence so that the patients get a high standard of care. The
      growth of information technology has provided us with tools which enable us to
      scrutinise vast amounts of data within a very short amount of time. EBM is a
      lifelong learning process and is an effort to make the most effective use of
      medical knowledge for best outcomes in terms of patient benefit and safety. It is
      important to understand the basic concepts of EBM and practice as well as
      propagate evidence based healthcare in Obstetrics and Gynaecology. CONCLUSION:
      Obstetricians and Gynaecologists need to be able to access and critically
      appraise the latest evidence in their area of expertise and apply it in clinical
      practice to provide best outcomes to women under their care.

PMID- 23543707
TI  - Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor
      immunotherapy with therapeutic antibodies.
AB  - In the last decade several therapeutic antibodies have been Federal Drug
      Administration (FDA) and European Medicines Agency (EMEA) approved. Although
      their mechanisms of action in vivo is not fully elucidated, antibody-dependent
      cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is presumed to
      be a key effector function. A substantial role of ADCC has been demonstrated in
      vitro and in mouse tumor models. However, a direct in vivo effect of ADCC in
      tumor reactivity in humans remains to be shown. Several studies revealed a
      predictive value of FcgammaRIIIa-V158F polymorphism in monoclonal antibody
      treatment, indicating a potential effect of ADCC on outcome for certain
      indications. Furthermore, the use of therapeutic antibodies after allogeneic
      hematopoietic stem cell transplantation is an interesting option. Studying the
      role of the FcgammaRIIIa-V158F polymorphism and the influence of Killer-cell
      Immunoglobuline-like Receptor (KIR) receptor ligand incompatibility on ADCC in
      this approach may contribute to future transplantation strategies. Despite the
      success of approved second-generation antibodies in the treatment of several
      malignancies, efforts are made to further augment ADCC in vivo by antibody
      engineering. Here, we review currently used therapeutic antibodies for which ADCC
      has been suggested as effector function.

PMID- 23543708
TI  - Activity and regulation of various forms of CwlJ, SleB, and YpeB proteins in
      degrading cortex peptidoglycan of spores of Bacillus species in vitro and during
      spore germination.
AB  - Germination of Bacillus spores requires degradation of a modified layer of
      peptidoglycan (PG) termed the spore cortex by two redundant cortex-lytic enzymes
      (CLEs), CwlJ and SleB, plus SleB's partner protein, YpeB. In this study, in vitro
      and in vivo analyses have been used to clarify the roles of individual SleB and
      YpeB domains in PG degradation. Purified mature Bacillus cereus SleB without its
      signal sequence (SleB(M)) and the SleB C-terminal catalytic domain (SleB(C))
      efficiently triggered germination of decoated Bacillus megaterium and Bacillus
      subtilis spores lacking endogenous CLEs; previously, SleB's N-terminal domain
      (SleB(N)) was shown to bind PG but have no enzymatic activity. YpeB lacking its
      putative membrane anchoring sequence (YpeB(M)) or its N- and C-terminal domains
      (YpeB(N) and YpeB(C)) alone did not exhibit degradative activity, but YpeB(N)
      inhibited SleB(M) and SleB(C) activity in vitro. The severe germination defect of
      B. subtilis cwlJ sleB or cwlJ sleB ypeB spores was complemented by ectopic
      expression of full-length sleB [sleB(FL)] and ypeB [ypeB(FL)], but normal levels
      of SleB(FL) in spores required normal spore levels of YpeB(FL) and vice versa.
      sleB(FL) or ypeB(FL) alone, sleB(FL) plus ypeB(C) or ypeB(N), and sleB(C) or
      sleB(N) plus ypeB(FL) did not complement the cortex degradation defect in cwlJ
      sleB ypeB spores. In addition, ectopic expression of sleB(FL) or cwlJ(FL) with a
      Glu-to-Gln mutation in a predicted active-site residue failed to restore the
      germination of cwlJ sleB spores, supporting the role of this invariant glutamate
      as the key catalytic residue in SleB and CwlJ.

PMID- 23543709
TI  - Characterization of the ospZ promoter in Shigella flexneri and its regulation by
      VirB and H-NS.
AB  - OspZ is an effector protein of the type III secretion system in Shigella spp.
      that downregulates the human inflammatory response during bacterial infection.
      The ospZ gene is located on the large virulence plasmid of Shigella. Many genes
      on this plasmid are transcriptionally repressed by the nucleoid structuring
      protein H-NS and derepressed by VirB, a DNA-binding protein that displays
      homology to the plasmid partitioning proteins ParB and SopB. In this study, we
      characterized the ospZ promoter and investigated its regulation by H-NS and VirB
      in Shigella flexneri. We show that H-NS represses and VirB partially derepresses
      the ospZ promoter. H-NS-mediated repression requires sequences located between 
      731 and -412 relative to the beginning of the ospZ gene. Notably, the VirB
      dependent derepression of ospZ requires the same VirB binding sites as are
      required for the VirB-dependent derepression of the divergent icsP gene. These
      sites are centered 425 bp upstream of the ospZ gene but over 1 kb upstream of the
      icsP transcription start site. Although these VirB binding sites lie closer to
      ospZ than icsP, the VirB-dependent increase in ospZ promoter activity is lower
      than that observed at the icsP promoter. This indicates that the proximity of
      VirB binding sites to Shigella promoters does not necessarily correlate with the
      level of VirB-dependent derepression. These findings have implications for
      virulence gene regulation in Shigella and other pathogens that control gene
      expression using mechanisms of transcriptional repression and derepression.

PMID- 23543710
TI  - Maltose uptake by the novel ABC transport system MusEFGK2I causes increased
      expression of ptsG in Corynebacterium glutamicum.
AB  - The Gram-positive Corynebacterium glutamicum efficiently metabolizes maltose by a
      pathway involving maltodextrin and glucose formation by 4-alpha
      glucanotransferase, glucose phosphorylation by glucose kinases, and maltodextrin
      degradation via maltodextrin phosphorylase and alpha-phosphoglucomutase. However,
      maltose uptake in C. glutamicum has not been investigated. Interestingly, the
      presence of maltose in the medium causes increased expression of ptsG in C.
      glutamicum by an unknown mechanism, although the ptsG-encoded glucose-specific
      EII permease of the phosphotransferase system itself is not required for maltose
      utilization. We identified the maltose uptake system as an ABC transporter
      encoded by musK (cg2708; ATPase subunit), musE (cg2705; substrate binding
      protein), musF (cg2704; permease), and musG (cg2703; permease) by combination of
      data obtained from characterization of maltose uptake and reanalyses of
      transcriptome data. Deletion of the mus gene cluster in C. glutamicum Deltamus
      abolished maltose uptake and utilization. Northern blotting and reverse
      transcription-PCR experiments revealed that musK and musE are transcribed
      monocistronically, whereas musF and musG are part of an operon together with
      cg2701 (musI), which encodes a membrane protein of unknown function with no
      homologies to characterized proteins. Characterization of growth and
      [(14)C]maltose uptake in the musI insertion strain C. glutamicum IMcg2701 showed
      that musI encodes a novel essential component of the maltose ABC transporter of
      C. glutamicum. Finally, ptsG expression during cultivation on different carbon
      sources was analyzed in the maltose uptake-deficient strain C. glutamicum
      Deltamus. Indeed, maltose uptake by the novel ABC transport system MusEFGK2I is
      required for the positive effect of maltose on ptsG expression in C. glutamicum.

PMID- 23543711
TI  - Relaxed cleavage specificity within the RelE toxin family.
AB  - Bacterial type II toxin-antitoxin systems are widespread in bacteria. Among them,
      the RelE toxin family is one of the most abundant. The RelE(K-12) toxin of
      Escherichia coli K-12 represents the paradigm for this family and has been
      extensively studied, both in vivo and in vitro. RelE(K-12) is an endoribonuclease
      that cleaves mRNAs that are translated by the ribosome machinery as these
      transcripts enter the A site. Earlier in vivo reports showed that RelE(K-12)
      cleaves preferentially in the 5'-end coding region of the transcripts in a codon
      independent manner. To investigate whether the molecular activity as well as the
      cleavage pattern are conserved within the members of this toxin family, RelE-like
      sequences were selected in Proteobacteria, Cyanobacteria, Actinobacteria, and
      Spirochaetes and tested in E. coli. Our results show that these RelE-like
      sequences are part of toxin-antitoxin gene pairs, and that they inhibit
      translation in E. coli by cleaving transcripts that are being translated. Primer
      extension analyses show that these toxins exhibit specific cleavage patterns in
      vivo, both in terms of frequency and location of cleavage sites. We did not
      observe codon-dependent cleavage but rather a trend to cleave upstream purines
      and between the second and third positions of codons, except for the
      actinobacterial toxin. Our results suggest that RelE-like toxins have evolved to
      rapidly and efficiently shut down translation in a large spectrum of bacterial
      species, which correlates with the observation that toxin-antitoxin systems are
      spreading by horizontal gene transfer.

PMID- 23543712
TI  - Posttranslational modification of flagellin FlaB in Shewanella oneidensis.
AB  - Shewanella oneidensis is a highly motile organism by virtue of a polar,
      glycosylated flagellum composed of flagellins FlaA and FlaB. In this study, the
      functional flagellin FlaB was isolated and analyzed with nano-liquid
      chromatography-mass spectrometry (MS) and tandem MS. In combination with the
      mutational analysis, we propose that the FlaB flagellin protein from S.
      oneidensis is modified at five serine residues with a series of novel O-linked
      posttranslational modifications (PTMs) that differ from each other by 14 Da.
      These PTMs are composed in part of a 274-Da sugar residue that bears a
      resemblance to the nonulosonic acids. The remainder appears to be composed of a
      second residue whose mass varies by 14 Da depending on the PTM. Further
      investigation revealed that synthesis of the glycans initiates with PseB and
      PseC, the first two enzymes of the Pse pathway. In addition, a number of lysine
      residues are found to be methylated by SO4160, an analogue of the lysine
      methyltransferase of Salmonella enterica serovar Typhimurium.

PMID- 23543713
TI  - A critical role for the cccA gene product, cytochrome c2, in diverting electrons
      from aerobic respiration to denitrification in Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae is a microaerophile that, when oxygen availability is
      limited, supplements aerobic respiration with a truncated denitrification
      pathway, nitrite reduction to nitrous oxide. We demonstrate that the cccA gene of
      Neisseria gonorrhoeae strain F62 (accession number NG0292) is expressed, but the
      product, cytochrome c2, accumulates to only low levels. Nevertheless, a cccA
      mutant reduced nitrite at about half the rate of the parent strain. We previously
      reported that cytochromes c4 and c5 transfer electrons to cytochrome oxidase cbb3
      by two independent pathways and that the CcoP subunit of cytochrome oxidase cbb3
      transfers electrons to nitrite. We show that mutants defective in either
      cytochrome c4 or c5 also reduce nitrite more slowly than the parent. By combining
      mutations in cccA (Deltac2), cycA (Deltac4), cycB (Deltac5), and ccoP (ccoP
      C368A), we demonstrate that cytochrome c2 is required for electron transfer from
      cytochrome c4 via the third heme group of CcoP to the nitrite reductase, AniA,
      and that cytochrome c5 transfers electrons to nitrite reductase by an independent
      pathway. We propose that cytochrome c2 forms a complex with cytochrome oxidase.
      If so, the redox state of cytochrome c2 might regulate electron transfer to
      nitrite or oxygen. However, our data are more consistent with a mechanism in
      which cytochrome c2 and the CcoQ subunit of cytochrome oxidase form alternative
      complexes that preferentially catalyze nitrite and oxygen reduction,
      respectively. Comparison with the much simpler electron transfer pathway for
      nitrite reduction in the meningococcus provides fascinating insights into niche
      adaptation within the pathogenic neisseriae.

PMID- 23543714
TI  - Three of four GlnR binding sites are essential for GlnR-mediated activation of
      transcription of the Amycolatopsis mediterranei nas operon.
AB  - In Amycolatopsis mediterranei U32, genes responsible for nitrate assimilation
      formed one operon, nasACKBDEF, whose transcription is induced by the addition of
      nitrate. Here, we characterized GlnR as a direct transcriptional activator for
      the nas operon. The GlnR-protected DNA sequences in the promoter region of the
      nas operon were characterized by DNase I footprinting assay, the previously
      deduced Streptomyces coelicolor double 22-bp GlnR binding consensus sequences
      comprising a1, b1, a2, and b2 sites were identified, and the sites were then
      mutated individually to test their roles in both the binding of GlnR in vitro and
      the GlnR-mediated transcriptional activation in vivo. The results clearly showed
      that only three GlnR binding sites (a1, b1, and b2 sites) were required by GlnR
      for its specific binding to the nas promoter region and efficient activation of
      the transcription of the nas operon in U32, while the a2 site seemed unnecessary.

PMID- 23543715
TI  - Multiple roles of RNase Y in Streptococcus pyogenes mRNA processing and
      degradation.
AB  - Control over mRNA stability is an essential part of gene regulation that involves
      both endo- and exoribonucleases. RNase Y is a recently identified
      endoribonuclease in Gram-positive bacteria, and an RNase Y ortholog has been
      identified in Streptococcus pyogenes (group A streptococcus [GAS]). In this
      study, we used microarray and Northern blot analyses to determine the S. pyogenes
      mRNA half-life of the transcriptome and to understand the role of RNase Y in
      global mRNA degradation and processing. We demonstrated that S. pyogenes has an
      unusually high mRNA turnover rate, with median and mean half-lives of 0.88 min
      and 1.26 min, respectively. A mutation of the RNase Y-encoding gene (rny) led to
      a 2-fold increase in overall mRNA stability. RNase Y was also found to play a
      significant role in the mRNA processing of virulence-associated genes as well as
      in the rapid degradation of rnpB read-through transcripts. From these results, we
      conclude that RNase Y is a pleiotropic regulator required for mRNA stability,
      mRNA processing, and removal of read-through transcripts in S. pyogenes.

PMID- 23543716
TI  - The delta subunit of RNA polymerase is required for rapid changes in gene
      expression and competitive fitness of the cell.
AB  - RNA polymerase (RNAP) is an extensively studied multisubunit enzyme required for
      transcription of DNA into RNA, yet the delta subunit of RNAP remains an enigmatic
      protein whose physiological roles have not been fully elucidated. Here, we
      identify a novel, so far unrecognized function of delta from Bacillus subtilis.
      We demonstrate that delta affects the regulation of RNAP by the concentration of
      the initiating nucleoside triphosphate ([iNTP]), an important mechanism crucial
      for rapid changes in gene expression in response to environmental changes.
      Consequently, we demonstrate that delta is essential for cell survival when
      facing a competing strain in a changing environment. Hence, although delta is not
      essential per se, it is vital for the cell's ability to rapidly adapt and survive
      in nature. Finally, we show that two other proteins, GreA and YdeB, previously
      implicated to affect regulation of RNAP by [iNTP] in other organisms, do not have
      this function in B. subtilis.

PMID- 23543717
TI  - Escherichia coli shapeshifters.

PMID- 23543718
TI  - Competence for natural genetic transformation in the Streptococcus bovis group
      streptococci S. infantarius and S. macedonicus.
AB  - Natural genetic transformation is common among many species of the genus
      Streptococcus, but it has never, or rarely, been reported for the Streptococcus
      pyogenes and S. bovis groups of species, even though many streptococcal
      competence genes and the competence regulators SigX, ComR, and ComS are well
      conserved in both groups. To explore the incidence of competence in the S. bovis
      group, 25 isolates of S. infantarius and S. macedonicus were surveyed by
      employing culture in chemically defined media devoid of peptide nutrients and
      treatment with synthetic candidate pheromone peptides predicted from the sequence
      of the gene comS. Approximately half of strains examined were transformable, many
      transforming at high rates comparable to those for the well-characterized
      streptococcal natural transformation systems. In S. infantarius, nanomolar
      amounts of the synthetic pheromone LTAWWGL induced robust but transient
      competence in high-density cultures, but mutation of the ComRS locus abolished
      transformation. We conclude that at least these two species of the S. bovis group
      retain a robust system of natural transformation regulated by a ComRS pheromone
      circuit and the alternative sigma factor SigX and infer that transformation is
      even more common among the streptococci than has been recognized. The tools
      presented here will facilitate targeted genetic manipulation in this group of
      streptococci.

PMID- 23543719
TI  - The Rcs stress response and accessory envelope proteins are required for de novo
      generation of cell shape in Escherichia coli.
AB  - Interactions with immune responses or exposure to certain antibiotics can remove
      the peptidoglycan wall of many Gram-negative bacteria. Though the spheroplasts
      thus created usually lyse, some may survive by resynthesizing their walls and
      shapes. Normally, bacterial morphology is generated by synthetic complexes
      directed by FtsZ and MreBCD or their homologues, but whether these classic
      systems can recreate morphology in the absence of a preexisting template is
      unknown. To address this question, we treated Escherichia coli with lysozyme to
      remove the peptidoglycan wall while leaving intact the inner and outer membranes
      and periplasm. The resulting lysozyme-induced (LI) spheroplasts recovered a rod
      shape after four to six generations. Recovery proceeded via a series of cell
      divisions that produced misshapen and branched intermediates before later progeny
      assumed a normal rod shape. Importantly, mutants defective in mounting the Rcs
      stress response and those lacking penicillin binding protein 1B (PBP1B) or LpoB
      could not divide or recover their cell shape but instead enlarged until they
      lysed. LI spheroplasts from mutants lacking the Lpp lipoprotein or PBP6 produced
      spherical daughter cells that did not recover a normal rod shape or that did so
      only after a significant delay. Thus, to regenerate normal morphology de novo, E.
      coli must supplement the classic FtsZ- and MreBCD-directed cell wall systems with
      activities that are otherwise dispensable for growth under normal laboratory
      conditions. The existence of these auxiliary mechanisms implies that they may be
      required for survival in natural environments, where bacterial walls can be
      damaged extensively or removed altogether.

PMID- 23543721
TI  - Oxidation of tricyclic antidepressant drugs with chloramine-T in acidic
      solutions: kinetic, mechanistic and thermodynamic studies.
AB  - The kinetics of the oxidation of two tricyclic antidepressants (TCA) namely,
      imipramine (IMP) and clomipramine (CLM) with sodium N-chloro-p-toluenesulfonamide
      or chloramine-T (CAT) in HClO4 medium was studied at 300 K. The two reactions
      followed identical kinetics with a first-order dependence of rate on [CAT]o and
      fractional order dependence on [TCA]o. The reaction is catalyzed by H(+) ions
      with a fractional order dependence. The reaction was studied at different
      temperatures and activation parameters were evaluated. The reaction constants
      involved in the mechanism were computed. The solvent isotope effect was studied
      using D2O. Addition of p-toluenesulfonamide retards the reaction rate. The rate
      increased with decreasing dielectric constant of the medium. Variation of ionic
      strength of the medium and addition of halide ions (Cl(-) or Br(-)) showed no
      effect on the rate. The stoichiometry of the reaction was found to be 1:1 and the
      oxidation products were identified as imipramine-5-N-oxide and clomipramine-5-N
      oxide. The rate of oxidation of IMP is faster than CLM. The observed results have
      been explained in terms of a mechanism and a relevant rate law has been deduced. 

PMID- 23543720
TI  - The Clostridium difficile cpr locus is regulated by a noncontiguous two-component
      system in response to type A and B lantibiotics.
AB  - The intestinal pathogen Clostridium difficile is known to grow only within the
      intestines of mammals, yet little is known about how the bacterium subsists in
      this environment. In the intestine, C. difficile must contend with innate
      defenses within the host, such as cationic antimicrobial peptides (CAMPs)
      produced by the host and the indigenous microbiota. In this study, we
      investigated the mechanism of activation and regulation of the CprABC transporter
      system, which provides resistance to multiple CAMPs and shows homology to the
      immunity systems of bacterial antimicrobial peptide producers. The CprABC system
      proved to be controlled by a noncontiguous two-component system consisting of the
      CprK sensor kinase and an orphan response regulator (CD3320; CprR). The CprK-CprR
      regulators were shown to activate cprABCK transcription in a manner similar to
      that by lantibiotic regulatory systems. Unlike lantibiotic producer regulation,
      regulation by CprK-CprR was activated by multiple lantibiotics produced by
      diverse Gram-positive bacteria. We identified a motif within these lantibiotics
      that is likely required for activation of cpr. Based on the similarities between
      the Cpr system and lantibiotic systems, we propose that the CprABC transporter
      and its regulators are relatives of lantibiotic systems that evolved to recognize
      multiple substrates to defend against toxins made by the intestinal microbiota.

PMID- 23543722
TI  - Evaluation of the Factors which Contribute to the Ocular Complaints in Computer
      Users.
AB  - CONTEXT: Use of information technology hardware given new heights to professional
      success rate and saves time but on the other hand its harmful effect has
      introduced an array of health related complaints causing hazards for our human
      health. Increased use of computers has led to an increase in the number of
      patients with ocular complaints which are being grouped together as computer
      vision syndrome (CVS). In view of that, this study was undertaken to find out the
      ocular complaints and the factors contributing to occurrence of such problems in
      computer users. AIMS: To evaluate the factors contributing to Ocular complaints
      in computer users in Teerthanker Mahaveer University, Moradabad, U.P. India.
      SETTINGS AND DESIGN: Community-based cross-sectional study of 150 subjects who
      work on computer for varying period of time in Teerthanker Mahaveer University,
      Moradabad, Uttar Pradesh. MATERIALS AND METHODS: Two hundred computer operators
      working in different institutes offices and bank of were selected randomly in
      Teerthanker Mahaveer University, Moradabad, and Uttar Pradesh. 16 were non
      responders 18 did not come for assessment and 16 were excluded due to complaints
      prior to computer use making no response rate Twenty-one did not participate in
      the study, making the no response rate 25%. Rest of the subjects (n = 150) were
      asked to fill a pre-tested questionnaire, after obtaining their verbal consent
      Depending on the average hours of usage in a day, they were categorized into
      three categories viz. <2 hrs, 2-6 hrs, >6 hrs of usage. All the responders were
      asked to come to the Ophthalmic OPD for further interview and assessment.
      STATISTICAL ANALYSIS USED: Simple proportions and Chi-square test. RESULTS: Among
      the 150 subjects studied major ocular complaint reported in descending order were
      eyestrain. (53%). Occurrence of eye strain, ( 53.8%), itching ( 47.6%) and
      burning (66.7%) in subjects using computer for more than 6 hours. distance from
      computer screen with respect to eyes, use of antiglare screen, taking frequent
      breaks, use of LCD monitor and adjustment of brightness of monitor screen bear a
      significant association with these ocular complaints in computer users.
      CONCLUSIONS: Eye strain is the most common ocular complaints among computer users
      working for more than 6 hours a day. We also found that maintaining ideal
      distance from screen, keeping level of eyes above the top of screen, taking
      frequent breaks, using LCD monitors and using antiglare screen and adjusting
      brightness levels according to workplace reduced these ocular complaints to a
      significant level.

PMID- 23543723
TI  - Con: Randomized controlled trials (RCT) have failed in the study of dialysis
      methods.
AB  - All progress in dialysis methods was made in research presented in case reports,
      case-control studies and other observational studies. On the contrary, randomized
      controlled trials (RCTs) did not bring any valuable results. Comparison of the
      value of peritoneal dialysis and hemodialysis (HD) in RCTs was not completed
      because of recruitment problems. Four RCTs in HD did not provide any useful data.
      The worst example was the National Cooperative Dialysis Study, which committed a
      Type II statistical error rejecting the time of dialysis as an important factor
      determining the quality of dialysis. This study also provided the basis for the
      establishment of the Kt/V index as a measure of dialysis adequacy. This index was
      accepted by the HD community, having been established in a sacrosanct RCT, led to
      short dialysis, and possibly higher mortality in the USA. The second trial (the
      HEMO study) committed a Type III statistical error asking the wrong question and
      did not bring any valuable results, but at least it did not lead to deterioration
      of dialysis outcomes in the USA. The third, the Frequent Hemodialysis Network
      Trial Group, did not bring forth any valuable results, but at least confirmed
      what was already known. The fourth, the Frequent Hemodialysis Network Nocturnal
      Trial, committed a Type II statistical error because of tremendous recruitment
      problems leading to an inadequate number of subjects. Moreover, the study
      methodology was absolutely unreliable.

PMID- 23543724
TI  - Pro: The value of randomized controlled studies in dialysis methods.

PMID- 23543725
TI  - Moderator's view: Are alternative dialysis strategies superior to conventional
      dialysis: what Popper tells us ...

PMID- 23543728
TI  - A qualitative analysis of GHB use among gay men: Reasons for use despite
      potential adverse outcomes.
AB  - This paper examines the use of gamma-hydroxybutyrate (GHB) among a sample of gay
      men in New York City, who identify GHB as their most frequently used club drug.
      The sample was drawn from a larger longitudinal investigation of club drug using
      men. Thematic analysis yielded findings regarding perceived stigma for GHB use,
      tolerance of potential adverse side effects, and reasons for why some prefer this
      substance to other club drugs. Specifically, our findings suggest that GHB is
      viewed unfavorably in many social circles, that side effects are tolerated by
      frequent GHB users, and that the drug is chosen over other substances because the
      short duration of action, energy boost, sleep assistance, increase in libido, and
      limited after-effects. Examining the reasons why men use this substance will lead
      to the development of GHB specific prevention strategies, which accurately
      address the consequences of use as well as the motivations that individuals
      possess for using the substance.

PMID- 23543729
TI  - Can the prognosis of individual patients with glioblastoma be predicted using an
      online calculator?
AB  - BACKGROUND: In an exploratory subanalysis of the European Organisation for
      Research and Treatment of Cancer and National Cancer Institute of Canada
      (EORTC/NCIC) trial data, Gorlia et al. identified a variety of factors that were
      predictive of overall survival, including therapy administered, age, extent of
      surgery, mini-mental score, administration of corticosteroids, World Health
      Organization (WHO) performance status, and O-methylguanine-DNA methyltransferase
      (MGMT) promoter methylation status. Gorlia et al. developed 3 nomograms, each
      intended to predict the survival times of patients with newly diagnosed
      glioblastoma on the basis of individual-specific combinations of prognostic
      factors. These are available online as a "GBM Calculator" and are intended for
      use in patient counseling. This study is an external validation of this
      calculator. METHOD: One hundred eighty-seven patients from 2 UK neurosurgical
      units who had histologically confirmed glioblastoma (WHO grade IV) had their
      information at diagnosis entered into the GBM calculator. A record was made of
      the actual and predicted median survival time for each patient. Statistical
      analysis was performed to assess the accuracy, precision, correlation, and
      discrimination of the calculator. RESULTS: The calculator gives both inaccurate
      and imprecise predictions. Only 23% of predictions were within 25% of the actual
      survival, and the percentage bias is 140% in our series. The coefficient of
      variance is 76%, where a smaller percentage would indicate greater precision.
      There is only a weak positive correlation between the predicted and actual
      survival among patients (R(2) of 0.07). Discrimination is inadequate as measured
      by a C-index of 0.62. CONCLUSIONS: The authors would not recommend the use of
      this tool in patient counseling. If departments were considering its use, we
      would advise that a similar validating exercise be undertaken.

PMID- 23543730
TI  - Common mental disorders and mortality in the West of Scotland Twenty-07 Study:
      comparing the General Health Questionnaire and the Hospital Anxiety and
      Depression Scale.
AB  - BACKGROUND: While various measures of common mental disorders (CMD) have been
      found to be associated with mortality, a comparison of how different measures
      predict mortality may improve our understanding of the association. This paper
      compares how the Hospital Anxiety and Depression Scale (HADS) and the 30-item
      General Health Questionnaire (GHQ-30) predict all cause and cause-specific
      mortality. METHODS: Data on 2547 men and women from two cohorts, aged
      approximately 39 and 55 years, from the West of Scotland Twenty-07 Study who were
      followed up for mortality over an average of 18.9 (SD 5.0) years. Scores were
      calculated for HADS depression (HADS-D), HADS Anxiety (HADS-A) and GHQ-30. Cox
      Proportional Hazards Models were used to determine how each CMD measure predicted
      mortality. RESULTS: After adjusting for serious physical illness, smoking, social
      class, alcohol, obesity, pulse rate and living alone, HRs (95% CI) per SD
      increase in score for all-cause mortality were: 1.15 (1.07 to 1.25) for HADS-D;
      1.13 (1.04 to 1.23) for GHQ-30 and 1.05 (0.96 to 1.14) for HADS-A. After the same
      adjustments, cardiovascular disease mortality was also related to HADS-D (HR 1.24
      (1.07 to 1.43)), to GHQ-30 (HR 1.24 (1.11 to 1.40)) and to HADS-A (HR 1.15 (1.01
      to 1.32)); respiratory mortality to GHQ-30 (HR 1.33 (1.13 to 1.55)) and mortality
      from other causes, excluding injuries, to HADS-D (HR 1.28 (1.05 to 1.55)).
      CONCLUSIONS: There were associations between CMD and both all-cause and cause
      specific mortality which were broadly similar for GHQ-30 and HADS-D and were
      still present after adjustment for important confounders and mediators.

PMID- 23543731
TI  - Paraspinal arteriovenous malformation Onyx embolization via an Ascent balloon.
AB  - Purely extradural lumbar spinal arteriovenous malformations (AVMs) are rare
      lesions that have diverse presentations and imaging features. The treatment of a
      symptomatic high flow paraspinal AVM with multiple feeders remains a challenge.
      We report the first use of an Ascent balloon (dual lumen balloon catheter) to
      deliver Onyx with excellent penetration to a paraspinal AVM. 

PMID- 23543732
TI  - Evaluation of antiemetic effect of intravenous palonosetron versus intravenous
      ondansetron in laparoscopic cholecystectomy: a randomized controlled trial.
AB  - OBJECTIVES: Incidence of postoperative nausea and vomiting (PONV), without active
      intervention, following laparoscopic cholecystectomy is unacceptably high. We
      evaluated the effectiveness of intravenous (IV) palonosetron in counteracting
      PONV during the first 24 hrs following laparoscopic cholecystectomy, using
      ondansetron as the comparator drug. MATERIALS AND METHODS: In a randomized,
      controlled, single blind, parallel group trial, single pre-induction IV doses of
      palonosetron (75 mcg) or ondansetron (4 mg) were administered to adult patients
      of either sex undergoing elective laparoscopic cholecystectomy. There were 49
      subjects per group. The pre-anesthetic regimen, anesthesia procedure and
      laparoscopic technique were uniform. The primary effectiveness measure was total
      number of PONV episodes in the 24 hrs period following end of surgery. The
      frequencies of individual nausea, retching and vomiting episodes, visual analog
      scale (VAS) score for nausea at 2, 6 and 24 hrs, use of rescue antiemetic
      (metoclopramide), number of complete responders (no PONV or use of rescue in 24
      hrs) and adverse events were secondary measures. RESULTS: There was no
      statistically significant difference between the groups in primary outcome.
      Similarly, the frequencies of nausea, retching and vomiting episodes, when
      considered individually, did not show significant difference. Nausea score was
      comparable at all time points. With palonosetron, 14 subjects (28.6%) required
      rescue medication while 13 (26.5%) did so with ondansetron. The number of
      complete responders was 14 (28.6%) and 16 (32.7%), respectively. Adverse events
      were few and mild. QTc prolongation was not encountered. CONCLUSION: Palonosetron
      is comparable to ondansetron for PONV prophylaxis in elective laparoscopic
      cholecystectomy when administered as single pre-induction dose.

PMID- 23543733
TI  - Multiple overlapping stents as monotherapy in the treatment of 'blister'
      pseudoaneurysms arising from the supraclinoid internal carotid artery: a single
      institution series and review of the literature.
AB  - BACKGROUND: The 'blister-type' aneurysm is one of the most devastating
      cerebrovascular lesions. Flow diversion with stent reconstruction is an emerging
      treatment and has shown promising initial results. OBJECTIVE: To evaluate the
      experience of one institution using stent reconstruction for pseudoaneurysms of
      the supraclinoid internal carotid artery and to compare with a review of the
      literature. METHODS: A retrospective review from one institution identified eight
      patients with 'blister' aneurysms over a 47-month period. The Raymond scale was
      used to classify the aneurysms. Clinical data were obtained using the modified
      Rankin Scale (mRS) and the National Institute of Health Stroke Scale. A
      literature review was performed and compared with our results. Clinical and
      angiographic data were obtained. RESULTS: After treatment, two aneurysms were
      Raymond class 1 (25%) and six were class 3 (75%). Of the class 3 aneurysms, two
      required retreatment, three (50%) progressed to complete occlusion and three
      (50%) had persistent aneurysm filling. Clinical data revealed two patients with
      mRS score of 0 (25%), five with mRS score of 1 (62.5%) and one with mRS score of
      2 (12.5%). From the literature review, residual filling was evident in nine
      patients (64.3%) and complete occlusion in four (28.6%). On follow-up
      angiography, nine (64.3%) were occluded, two (14.3%) had residual neck filling
      and one (7.1%) had persistent aneurysm filling. Thirteen patients (92.9%) had an
      mRS score of 2 or better. Combining the available experience, patients
      demonstrated either improvement (n=9, 41%) or stability (n=11, 50%). Only two
      (9%) had progression requiring retreatment. CONCLUSIONS: Endovascular stent
      remodeling of 'blister-type' aneurysms is a safe and effective strategy.

PMID- 23543734
TI  - Multispecificity of immunoglobulin M antibodies raised against advanced glycation
      end products: involvement of electronegative potential of antigens.
AB  - BACKGROUND: Advanced glycation end products (AGEs) can act as neoantigens to
      trigger immune responses. RESULTS: Natural IgM antibodies against AGEs recognize
      multiple molecules, including DNA and chemically modified proteins. CONCLUSION:
      There is a close relationship between the formation of AGEs and innate immune
      responses. SIGNIFICANCE: Our findings highlight AGEs and related modified
      proteins as a source of multispecific natural antibodies Advanced glycation end
      products (AGEs) are a heterogeneous and complex group of compounds that are
      formed when reducing sugars, such as dehydroascorbic acid, react in a
      nonenzymatic way with amino acids in proteins and other macromolecules. AGEs are
      prevalent in the diabetic vasculature and contribute to the development of
      atherosclerosis. The presence and accumulation of AGEs in many different cell
      types affect the extracellular and intracellular structure and function. In the
      present study, we studied the immune response to the dehydroascorbic acid-derived
      AGEs and provide multiple lines of evidence suggesting that the AGEs could be an
      endogenous source of innate epitopes recognized by natural IgM antibodies.
      Prominent IgM titers to the AGEs were detected in the sera of normal mice and
      were significantly accelerated by the immunization with the AGEs. Patients with
      systemic lupus erythematosus (SLE), a potentially fatal systemic autoimmune
      disease characterized by the increased production of autoantibodies, showed
      significantly higher serum levels of the IgM titer against the AGEs than healthy
      individuals. A progressive increase in the IgM response against the AGEs was also
      observed in the SLE-prone mice. Strikingly, a subset of monoclonal antibodies,
      showing a specificity toward the AGEs, prepared from normal mice immunized with
      the AGEs and from the SLE mice cross-reacted with the double-stranded DNA.
      Moreover, they also cross-reacted with several other modified proteins, including
      the acetylated proteins, suggesting that the multiple specificity of the
      antibodies might be ascribed, at least in part, to the increased electronegative
      potential of the proteins. These findings suggest that the protein modification
      by the endogenous carbonyl compounds, generating electronegative proteins, could
      be a source of multispecific natural antibodies.

PMID- 23543735
TI  - Lysine acetyltransferase GCN5 potentiates the growth of non-small cell lung
      cancer via promotion of E2F1, cyclin D1, and cyclin E1 expression.
AB  - The lysine acetyltransferases play crucial but complex roles in cancer
      development. GCN5 is a lysine acetyltransferase that generally regulates gene
      expression, but its role in cancer development remains largely unknown. In this
      study, we report that GCN5 is highly expressed in non-small cell lung cancer
      tissues and that its expression correlates with tumor size. We found that the
      expression of GCN5 promotes cell growth and the G1/S phase transition in multiple
      lung cancer cell lines. Further study revealed that GCN5 regulates the expression
      of E2F1, cyclin D1, and cyclin E1. Our reporter assays indicated that the
      expression of GCN5 enhances the activities of the E2F1, cyclin D1, and cyclin E1
      promoters. ChIP experiments suggested that GCN5 binds directly to these promoters
      and increases the extent of histone acetylation within these regions. Mechanistic
      studies suggested that GCN5 interacts with E2F1 and is recruited by E2F1 to the
      E2F1, cyclin D1, and cyclin E1 promoters. The function of GCN5 in lung cancer
      cells is abrogated by the knockdown of E2F1. Finally, we confirmed that GCN5
      regulates the expression of E2F1, cyclin D1, and cyclin E1 and potentiates lung
      cancer cell growth in a mouse tumor model. Taken together, our results
      demonstrate that GCN5 specifically potentiates lung cancer growth by directly
      promoting the expression of E2F1, cyclin D1, and cyclin E1 in an E2F1-dependent
      manner. Our study identifies a specific and novel function of GCN5 in lung cancer
      development and suggests that the GCN5-E2F1 interaction represents a potential
      target for lung cancer treatment.

PMID- 23543736
TI  - Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel potentiator of cyclin
      dependent kinases to enhance cell proliferation independently of its hydrolase
      activity.
AB  - Dysregulation of cell proliferation and the cell cycle are associated with
      various diseases, such as cancer. Cyclin-dependent kinases (CDKs) play central
      roles in cell proliferation and the cell cycle. Ubiquitin C-terminal hydrolase L1
      (UCH-L1) is expressed in a restricted range of tissues, including the brain and
      numerous types of cancer. However, the molecular functions of UCH-L1 remain
      elusive. In this study, we found that UCH-L1 physically interacts with CDK1,
      CDK4, and CDK5, enhancing their kinase activity. Using several mutants of UCH-L1,
      we showed that this enhancement is dependent upon interaction levels between UCH
      L1 and CDKs but is independent of the known ubiquitin-related functions of UCH
      L1. Gain- and loss-of-function studies revealed that UCH-L1 enhances
      proliferation of multiple cell types, including human cancer cells. Inhibition of
      the interaction between UCH-L1 and cell cycle-associated CDK resulted in the
      abolishment of UCH-L1-induced enhancement of cell proliferation. RNA interference
      of UCH-L1 reduced the growth of human xenograft tumors in mice. We concluded that
      UCH-L1 is a novel regulator of the kinase activities of CDKs. We believe that our
      findings from this study will significantly contribute to our understanding of
      cell cycle-associated diseases.

PMID- 23543738
TI  - Hyperoxidation of peroxiredoxins 2 and 3: rate constants for the reactions of the
      sulfenic acid of the peroxidatic cysteine.
AB  - Typical 2-Cys peroxiredoxins (Prxs) react rapidly with H2O2 to form a sulfenic
      acid, which then condenses with the resolving cysteine of the adjacent Prx in the
      homodimer or reacts with another H2O2 to become hyperoxidized. Hyperoxidation
      inactivates the Prx and is implicated in cell signaling. Prxs vary in
      susceptibility to hyperoxidation. We determined rate constants for disulfide
      formation and hyperoxidation for human recombinant Prx2 and Prx3 by analyzing the
      relative proportions of hyperoxidized and dimeric products using mass
      spectrometry as a function of H2O2 concentration (in the absence of reductive
      cycling) and in competition with catalase at a fixed concentration of H2O2. This
      gave a second order rate constant for hyperoxidation of 12,000 M(-1) s(-1) and a
      rate constant for disulfide formation of 2 s(-1) for Prx2. A similar
      hyperoxidation rate constant for Prx3 was measured, but its rate of disulfide
      formation was ~10-fold higher, making it is more resistant than Prx2 to
      hyperoxidation. There are two active sites within the homodimer, and at low H2O2
      concentrations one site was hyperoxidized and the other present as a disulfide.
      Prx with two hyperoxidized sites formed progressively at higher H2O2
      concentrations. Although the sulfenic acid forms of Prx2 and Prx3 are ~1000-fold
      less reactive with H2O2 than their active site thiols, they react several orders
      of magnitude faster than most reduced thiol proteins. This observation has
      important implications for understanding the mechanism of peroxide sensing in
      cells.

PMID- 23543737
TI  - Loss of calcium/calmodulin-dependent protein kinase II activity in cortical
      astrocytes decreases glutamate uptake and induces neurotoxic release of ATP.
AB  - The extent of calcium/calmodulin-dependent protein kinase II (CaMKII)
      inactivation in the brain after ischemia correlates with the extent of damage. We
      have previously shown that a loss of CaMKII activity in neurons is detrimental to
      neuronal viability by inducing excitotoxic glutamate release. In the current
      study we extend these findings to show that the ability of astrocytes to buffer
      extracellular glutamate is reduced when CaMKII is inhibited. Furthermore, CaMKII
      inhibition in astrocytes is associated with the rapid onset of intracellular
      calcium oscillations. Surprisingly, this rapid calcium influx is blocked by the N
      type calcium channel antagonist, omega-conotoxin. Although the function of N-type
      calcium channels within astrocytes is controversial, these voltage-gated calcium
      channels have been linked to calcium-dependent vesicular gliotransmitter release.
      When extracellular glutamate and ATP levels are measured after CaMKII inhibition
      within our enriched astrocyte cultures, no alterations in glutamate levels are
      observed, whereas ATP levels in the extracellular environment significantly
      increase. Extracellular ATP accumulation associated with CaMKII inhibition
      contributes both to calcium oscillations within astrocytes and ultimately
      cortical neuron toxicity. Thus, a loss of CaMKII signaling within astrocytes
      dysregulates glutamate uptake and supports ATP release, two processes that would
      compromise neuronal survival after ischemic/excitotoxic insults.

PMID- 23543739
TI  - Physical and functional interactions of a monothiol glutaredoxin and an iron
      sulfur cluster carrier protein with the sulfur-donating radical S-adenosyl-L
      methionine enzyme MiaB.
AB  - The biosynthesis of iron sulfur (FeS) clusters, their trafficking from initial
      assembly on scaffold proteins via carrier proteins to final incorporation into
      FeS apoproteins, is a highly coordinated process enabled by multiprotein systems
      encoded in iscRSUAhscBAfdx and sufABCDSE operons in Escherichia coli. Although
      these systems are believed to encode all factors required for initial cluster
      assembly and transfer to FeS carrier proteins, accessory factors such as
      monothiol glutaredoxin, GrxD, and the FeS carrier protein NfuA are located
      outside of these defined systems. These factors have been suggested to function
      both as shuttle proteins acting to transfer clusters between scaffold and carrier
      proteins and in the final stages of FeS protein assembly by transferring clusters
      to client FeS apoproteins. Here we implicate both of these factors in client
      protein interactions. We demonstrate specific interactions between GrxD, NfuA,
      and the methylthiolase MiaB, a radical S-adenosyl-L-methionine-dependent enzyme
      involved in the maturation of a subset of tRNAs. We show that GrxD and NfuA
      physically interact with MiaB with affinities compatible with an in vivo
      function. We furthermore demonstrate that NfuA is able to transfer its cluster in
      vitro to MiaB, whereas GrxD is unable to do so. The relevance of these
      interactions was demonstrated by linking the activity of MiaB with GrxD and NfuA
      in vivo. We observe a severe defect in in vivo MiaB activity in cells lacking
      both GrxD and NfuA, suggesting that these proteins could play complementary roles
      in maturation and repair of MiaB.

PMID- 23543740
TI  - Inducible tumor necrosis factor (TNF) receptor-associated factor-1 expression
      couples the canonical to the non-canonical NF-kappaB pathway in TNF stimulation.
AB  - The NF-kappaB transcription factor mediates the inflammatory response through
      distinct (canonical and non-canonical) signaling pathways. The mechanisms
      controlling utilization of either of these pathways are largely unknown. Here we
      observe that TNF stimulation induces delayed NF-kappaB2/p100 processing and
      investigate the coupling mechanism. TNF stimulation induces TNF-associated factor
      1 (TRAF-1) that directly binds NF-kappaB-inducing kinase (NIK) and stabilizes it
      from degradation by disrupting its interaction with TRAF2.cIAP2 ubiquitin ligase
      complex. We show that TRAF1 depletion prevents TNF-induced NIK stabilization and
      reduces p52 production. To further examine the interactions of TRAF1 and NIK with
      NF-kappaB2/p100 processing, we mathematically modeled TRAF1.NIK as a coupling
      signaling complex and validated computational inference by siRNA knockdown to
      show non-canonical pathway activation is dependent not only on TRAF1 induction
      but also NIK stabilization by forming TRAF1.NIK complex. Thus, these integrated
      computational-experimental studies of TNF-induced TRAF1 expression identified
      TRAF1.NIK as a central complex linking canonical and non-canonical pathways by
      disrupting the TRAF2-cIAP2 ubiquitin ligase complex. This feed-forward kinase
      pathway is essential for the activation of non-canonical pathway.

PMID- 23543741
TI  - The structural location of DNA lesions in nucleosome core particles determines
      accessibility by base excision repair enzymes.
AB  - BACKGROUND: Base excision repair is hindered by nucleosomes. RESULTS: Outwardly
      oriented uracils near the nucleosome center are efficiently cleaved; however,
      polymerase beta is strongly inhibited at these sites. CONCLUSION: The histone
      octamer presents different levels of constraints on BER, dependent on the
      structural requirements for enzyme activity. SIGNIFICANCE: Chromatin remodeling
      is necessary to prevent accumulation of aborted intermediates in nucleosomes.
      Packaging of DNA into chromatin affects accessibility of DNA regulatory factors
      involved in transcription, replication, and repair. Evidence suggests that even
      in the nucleosome core particle (NCP), accessibility to damaged DNA is hindered
      by the presence of the histone octamer. Base excision repair is the major pathway
      in mammalian cells responsible for correcting a large number of chemically
      modified bases. We have measured the repair of site-specific uracil and single
      nucleotide gaps along the surface of the NCP. Our results indicate that removal
      of DNA lesions is greatly dependent on their rotational and translational
      positioning in NCPs. Significantly, the rate of uracil removal with outwardly
      oriented DNA backbones is 2-10-fold higher than those with inwardly oriented
      backbones. In general, uracils with inwardly oriented backbones farther away from
      the dyad center of the NCP are more accessible than those near the dyad. The
      translational positioning of outwardly oriented gaps is the key factor driving
      gap filling activity. An outwardly oriented gap near the DNA ends exhibits a 3
      fold increase in gap filling activity as compared with one near the dyad with the
      same rotational orientation. Near the dyad, uracil DNA glycosylase/APE1 removes
      an outwardly oriented uracil efficiently; however, polymerase beta activity is
      significantly inhibited at this site. These data suggest that the hindrance
      presented by the location of a DNA lesion is dependent on the structural
      requirements for enzyme catalysis. Therefore, remodeling at DNA damage sites in
      NCPs is critical for preventing accumulation of aborted intermediates and
      ensuring completion of base excision repair.

PMID- 23543742
TI  - Trafficking of the transcription factor Nrf2 to promyelocytic leukemia-nuclear
      bodies: implications for degradation of NRF2 in the nucleus.
AB  - Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin
      ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is
      an extensively studied mechanism for regulating the cellular level of Nrf2.
      Although mechanistic details are lacking, reports abound that Nrf2 can also be
      degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for
      sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which
      enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3
      modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to
      promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key
      components of PML-NBs did not contain biologically active Keap1 but contained
      modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3
      ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically
      inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML
      NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this
      decrease, resulting in elevated levels of polysumoylated Nrf2 that was also
      ubiquitylated. Wild-type RNF4 accelerated the half-life (t&frac12;) of Nrf2,
      measured in PML-NB-enriched cell fractions. These results suggest that RNF4
      mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent
      degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for
      sumoylation and provides a novel mechanism for its degradation in the nucleus,
      independent of Keap1.

PMID- 23543744
TI  - Anterior Dislocation of the Shoulder Due to an Idiopathic Deltoid Contracture-the
      Report of a Rare Presentation.
AB  - Post injection fibrosis leading to muscle contracture is a known complication.
      Deltoid fibrosis is known to occur following trauma or an intramuscular
      injection. Idiopathic Deltoid fibrosis leading to abduction contracture and
      anterior dislocation of the shoulder is a rare entity. Prompt diagnosis and
      surgery by distal release of fibrosed Deltoid muscle will lead to good functional
      recovery.

PMID- 23543743
TI  - Semiquinone and cluster N6 signals in His-tagged proton-translocating
      NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli.
AB  - NADH:ubiquinone oxidoreductase (complex I) pumps protons across the membrane
      using downhill redox energy. The Escherichia coli complex I consists of 13
      different subunits named NuoA-N coded by the nuo operon. Due to the low abundance
      of the protein and some difficulty with the genetic manipulation of its large ~15
      kb operon, purification of E. coli complex I has been technically challenging.
      Here, we generated a new strain in which a polyhistidine sequence was inserted
      upstream of nuoE in the operon. This allowed us to prepare large amounts of
      highly pure and active complex I by efficient affinity purification. The purified
      complex I contained 0.94 +/- 0.1 mol of FMN, 29.0 +/- 0.37 mol of iron, and 1.99
      +/- 0.07 mol of ubiquinone/1 mol of complex I. The extinction coefficient of
      isolated complex I was 495 mM(-1) cm(-1) at 274 nm and 50.3 mM(-1) cm(-1) at 410
      nm. NADH:ferricyanide activity was 219 +/- 9.7 MUmol/min/mg by using HEPES-Bis
      Tris propane, pH 7.5. Detailed EPR analyses revealed two additional iron-sulfur
      cluster signals, N6a and N6b, in addition to previously assigned signals.
      Furthermore, we found small but significant semiquinone signal(s), which have
      been reported only for bovine complex I. The line width was ~12 G, indicating its
      neutral semiquinone form. More than 90% of the semiquinone signal originated from
      the single entity with P&frac12; (half-saturation power level) = 1.85 milliwatts.
      The semiquinone signal(s) decreased by 60% when with asimicin, a potent complex I
      inhibitor. The functional role of semiquinone and the EPR assignment of clusters
      N6a/N6b are discussed.

PMID- 23543745
TI  - Randomised trials on return-to-work programmes for major depressive disorder.

PMID- 23543746
TI  - Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?
AB  - The authors examined whether early adolescents (N = 90) solicit self-enhancing
      feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback
      congruent with self-views, even when these views are negative). Sixth, seventh,
      and eighth graders first completed a self-perception measure and then selected
      whether to receive positive or negative feedback from an unknown peer in
      different domains of self. Results were consistent with self-verification theory;
      adolescents who perceived themselves as having both strengths and weaknesses were
      more likely to seek negative feedback regarding a self-perceived weakness
      compared to a self-perceived strength. The authors found similar support for self
      verification processes when they considered the entire sample regardless of
      perceived strengths and weaknesses; hierarchical linear modeling (HLM) examined
      the predictive power of ratings of self-perceived ability, certainty, and
      importance on feedback seeking for all participants and provided additional
      evidence of self-verification strivings in adolescence.

PMID- 23543747
TI  - Translesion synthesis past acrolein-derived DNA adducts by human mitochondrial
      DNA polymerase gamma.
AB  - Acrolein, a mutagenic aldehyde, is produced endogenously by lipid peroxidation
      and exogenously by combustion of organic materials, including tobacco products.
      Acrolein reacts with DNA bases forming exocyclic DNA adducts, such as gamma
      hydroxy-1,N(2)-propano-2'-deoxyguanosine (gamma-HOPdG) and gamma-hydroxy-1,N(6)
      propano-2'-deoxyadenosine (gamma-HOPdA). The bulky gamma-HOPdG adduct blocks DNA
      synthesis by replicative polymerases but can be bypassed by translesion synthesis
      polymerases in the nucleus. Although acrolein-induced adducts are likely to be
      formed and persist in mitochondrial DNA, animal cell mitochondria lack
      specialized translesion DNA synthesis polymerases to tolerate these lesions.
      Thus, it is important to understand how pol gamma, the sole mitochondrial DNA
      polymerase in human cells, acts on acrolein-adducted DNA. To address this
      question, we investigated the ability of pol gamma to bypass the minor groove
      gamma-HOPdG and major groove gamma-HOPdA adducts using single nucleotide
      incorporation and primer extension analyses. The efficiency of pol gamma
      catalyzed bypass of gamma-HOPdG was low, and surprisingly, pol gamma preferred to
      incorporate purine nucleotides opposite the adduct. Pol gamma also exhibited ~2
      fold lower rates of excision of the misincorporated purine nucleotides opposite
      gamma-HOPdG compared with the corresponding nucleotides opposite dG. Extension of
      primers from the termini opposite gamma-HOPdG was accomplished only following
      error-prone purine nucleotide incorporation. However, pol gamma preferentially
      incorporated dT opposite the gamma-HOPdA adduct and efficiently extended primers
      from the correctly paired terminus, indicating that gamma-HOPdA is probably
      nonmutagenic. In summary, our data suggest that acrolein-induced exocyclic DNA
      lesions can be bypassed by mitochondrial DNA polymerase but, in the case of the
      minor groove gamma-HOPdG adduct, at the cost of unprecedented high mutation
      rates.

PMID- 23543748
TI  - Role of replication protein A in double holliday junction dissolution mediated by
      the BLM-Topo IIIalpha-RMI1-RMI2 protein complex.
AB  - The conserved BTR complex, composed of the Bloom's syndrome helicase (BLM),
      topoisomerase IIIalpha, RMI1, and RMI2, regulates homologous recombination in
      favor of non-crossover formation via the dissolution of the double Holliday
      Junction (dHJ). Here we show enhancement of the BTR-mediated dHJ dissolution
      reaction by the heterotrimeric single-stranded DNA binding protein replication
      protein A (RPA). Our results suggest that RPA acts by sequestering a single
      stranded DNA intermediate during dHJ dissolution. We provide evidence that RPA
      physically interacts with RMI1. The RPA interaction domain in RMI1 has been
      mapped, and RMI1 mutants impaired for RPA interaction have been generated.
      Examination of these mutants ascertains the significance of the RMI1-RPA
      interaction in dHJ dissolution. Our results thus implicate RPA as a cofactor of
      the BTR complex in dHJ dissolution.

PMID- 23543749
TI  - Regulatory interactions between a bacterial tyrosine kinase and its cognate
      phosphatase.
AB  - The cyclic process of autophosphorylation of the C-terminal tyrosine cluster (YC)
      of a bacterial tyrosine kinase and its subsequent dephosphorylation following
      interactions with a counteracting tyrosine phosphatase regulates diverse
      physiological processes, including the biosynthesis and export of polysaccharides
      responsible for the formation of biofilms or virulence-determining capsules. We
      provide here the first detailed insight into this hitherto uncharacterized
      regulatory interaction at residue-specific resolution using Escherichia coli Wzc,
      a canonical bacterial tyrosine kinase, and its opposing tyrosine phosphatase,
      Wzb. The phosphatase Wzb utilizes a surface distal to the catalytic elements of
      the kinase, Wzc, to dock onto its catalytic domain (WzcCD). WzcCD binds in a
      largely YC-independent fashion near the Wzb catalytic site, inducing allosteric
      changes therein. YC dephosphorylation is proximity-mediated and reliant on the
      elevated concentration of phosphorylated YC near the Wzb active site resulting
      from WzcCD docking. Wzb principally recognizes the phosphate of its
      phosphotyrosine substrate and further stabilizes the tyrosine moiety through ring
      stacking interactions with a conserved active site tyrosine.

PMID- 23543750
TI  - Olanzapine induced neuroleptic malignant syndrome.
AB  - An 18 year old male diagnosed as a case of bipolar affective disorder (BPAD),
      developed neuroleptic malignant syndrome (NMS) following treatment with
      olanzapine (20 mg per day), an atypical antipsychotic drug. NMS is usually seen
      with typical antipsychotic drugs. The patient was diagnosed as a case of NMS,
      offending agent was immediately withdrawn and prompt treatment with bromocriptine
      and levodopa produced a good recovery. The various features of the case are
      discussed in view of the potential mortality of the syndrome.

PMID- 23543751
TI  - ZmLEA3, a multifunctional group 3 LEA protein from maize (Zea mays L.), is
      involved in biotic and abiotic stresses.
AB  - Late embryogenesis abundant (LEA) proteins accumulate to high levels during the
      late stage of seed maturation and in response to water deficit, and are involved
      in protecting higher plants from damage caused by environmental stresses,
      especially drought. In the present study, a novel maize (Zea mays L.) group 3 LEA
      gene, ZmLEA3, was identified and later characterized using transgenic tobacco
      plants to investigate its functions in abiotic and biotic stresses. Transcript
      accumulation demonstrated that ZmLEA3 was induced in leaves by high salinity, low
      temperature, osmotic and oxidative stress as well as by signaling molecules such
      as ABA, salicylic acid (SA) and methyl jasmonate (MeJA). The transcript of ZmLEA3
      could also be induced by pathogens [Pseudomonas syringae pv. tomato DC3000 (pst
      dc3000)]. ZmLEA3 is located in the cytosol and the nucles. Further study
      indicated that the ZmLEA3 protein could bind Mn(2+), Fe(3+), Cu(2+) and Zn(2+).
      Overexpression of ZmLEA3 in transgenic tobacco (Nicotiana tabacum) and yeast
      (GS115) conferred tolerance to osmotic and oxidative stresses. Interestingly, we
      also found that overexpression of ZmLEA3 in transgenic tobacco increased the
      hypersensitive cell death triggered by pst dc3000 and enhanced the expression of
      PR1a, PR2 and PR4 when compared with the wild type. Thus, we proposed that the
      ZmLEA3 protein plays a role in protecting plants from damage by protecting
      protein structure and binding metals under osmotic and oxidative stresses. In
      addition, ZmLEA3 may also enhance transgenic plant tolerance to biotic stress.

PMID- 23543752
TI  - The AP-1 MU adaptin is required for KNOLLE localization at the cell plate to
      mediate cytokinesis in Arabidopsis.
AB  - Formation of clathrin-coated vesicles (CCVs) requires the scaffolding adaptor
      protein (AP) complexes, which are conserved across all eukaryotes. The
      Arabidopsis genome encodes five AP complexes (AP-1 to AP-5), and each complex
      consists of four subunits. In this study, we characterized the poorly defined AP
      1 complex by using genetics, proteomics and live cell imaging. We showed that the
      AP-1 u adaptin subunit (AP1M2) was localized to the trans-Golgi network (TGN) and
      interacted physically with the AP-1 subunits in Arabidopsis. During treatment
      with brefeldin A (BFA), the functional fluorophore-tagged AP1M2 relocated to the
      BFA compartment. The AP1M2 loss-of-function mutant ap1m2 displayed deleterious
      growth defects, which were particularly evident in the compromised cytokinesis
      that was revealed by the presence of cell wall stubs in multinucleate cells.
      Immunolocalization of the cytokinesis-specific syntaxin KNOLLE (KN) in ap1m2
      showed that KN was mislocalized and aggregated around the division plane, while a
      secretory marker targeting to the cell plate remained unaffected. Taken together,
      we propose that the AP-1 complex is required for cell plate-targeted trafficking
      of KN in dividing plant cells, and that it has a common role in mediating plant
      and yeast/animal cytokinesis systems which are fundamentally different.

PMID- 23543753
TI  - Cutting Edge: memory regulatory t cells require IL-7 and not IL-2 for their
      maintenance in peripheral tissues.
AB  - Thymic Foxp3-expressing regulatory T cells are activated by peripheral self
      antigen to increase their suppressive function, and a fraction of these cells
      survive as memory regulatory T cells (mTregs). mTregs persist in nonlymphoid
      tissue after cessation of Ag expression and have enhanced capacity to suppress
      tissue-specific autoimmunity. In this study, we show that murine mTregs express
      specific effector memory T cell markers and localize preferentially to hair
      follicles in skin. Memory Tregs express high levels of both IL-2Ralpha and IL
      7Ralpha. Using a genetic-deletion approach, we show that IL-2 is required to
      generate mTregs from naive CD4(+) T cell precursors in vivo. However, IL-2 is not
      required to maintain these cells in the skin and skin-draining lymph nodes.
      Conversely, IL-7 is essential for maintaining mTregs in skin in the steady state.
      These results elucidate the fundamental biology of mTregs and show that IL-7
      plays an important role in their survival in skin.

PMID- 23543754
TI  - Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a
      chromatin-remodeling complex that contains KAP1/TRIM28.
AB  - Regulatory T cells (Tregs) play a pivotal role in the maintenance of
      immunological self-tolerance. Deficiency or dysfunction of Tregs leads to severe
      autoimmune diseases. Although the forkhead/winged-helix family member FOXP3 is
      critical for Treg differentiation and function, the molecular basis for FOXP3
      function remains unclear. In this study, we identified and characterized a human
      specific FOXP3-interacting protein, referred to as FIK (FOXP3-interacting KRAB
      domain-containing protein). FIK is highly expressed in Tregs and acts as a
      bridging molecule to link FOXP3 with the chromatin-remodeling scaffold protein
      KAP1 (TIF-1beta/TRIM28). Disruption of the FOXP3-FIK-KAP1 complex in Tregs
      restored expression of FOXP3-target genes and abrogated the suppressor activity
      of the Tregs. These data demonstrate a critical role for FIK in regulating FOXP3
      activity and Treg function.

PMID- 23543755
TI  - Impaired neutrophil function in 24p3 null mice contributes to enhanced
      susceptibility to bacterial infections.
AB  - Lipocalin 24p3 (24p3) is a neutrophil secondary granule protein. 24p3 is also a
      siderocalin, which binds several bacterial siderophores. It was therefore
      proposed that synthesis and secretion of 24p3 by stimulated macrophages or
      release of 24p3 upon neutrophil degranulation sequesters iron-laden siderophores
      to attenuate bacterial growth. Accordingly, 24p3-deficient mice are susceptible
      to bacterial pathogens for which siderophores would normally be chelated by 24p3.
      Specific granule deficiency (SGD) is a rare congenital disorder characterized by
      complete absence of proteins in secondary granules. Neutrophils from SGD
      patients, who are prone to bacterial infections, lack normal functions, but the
      potential role of 24p3 in neutrophil dysfunction in SGD is not known. In this
      study, we show that neutrophils from mice genetically deficient for lipocalin
      24p3 (24p3(-/-)) are defective in many neutrophil functions. Specifically,
      neutrophils in 24p3(-/-) mice do not extravasate to sites of infection and are
      defective for chemotaxis. A transcriptome analysis revealed that genes that
      control cytoskeletal reorganization are selectively suppressed in 24p3(-/-)
      neutrophils. Additionally, small regulatory RNAs (microRNAs) that control
      upstream regulators of cytoskeletal proteins are also increased in 24p3(-/-)
      neutrophils. Further, 24p3(-/-) neutrophils failed to phagocytose bacteria, which
      may account for the enhanced sensitivity of 24p3(-/-) mice to both intracellular
      (Listeria monocytogenes) and extracellular (Candida albicans and Staphylococcus
      aureus) pathogens. Listeria does not secrete siderophores, and additionally, the
      siderophore secreted by Candida is not sequestered by 24p3. Therefore, the
      heightened sensitivity of 24p3(-/-) mice to these pathogens is not due to
      sequestration of siderophores limiting iron availability, but is a consequence of
      impaired neutrophil function.

PMID- 23543756
TI  - Noradrenergic neurons regulate monocyte trafficking and mortality during gram
      negative peritonitis in mice.
AB  - Effective host defense requires a robust, yet self-limited response to pathogens.
      A poorly calibrated response can lead to either bacterial dissemination due to
      insufficient inflammation or organ injury due to excessive inflammation. Recent
      evidence suggests that the cholinergic anti-inflammatory reflex helps calibrate
      the immune response. However, the influence of peripheral noradrenergic neurons,
      which are primarily sympathetic neurons, in regulating immunity remains
      incompletely characterized. Using a model of 6-hydroxydopamine-mediated
      noradrenergic nerve ablation, we show that elimination of noradrenergic neurons
      improves survival during Klebsiella pneumoniae peritonitis (67 versus 23%, p <
      0.005) in mice. The survival benefit results from enhanced MCP-1-dependent
      monocyte recruitment and a subsequent decrease in bacterial loads. Splenectomy
      eliminated both the survival benefit of 6-hydroxydopamine and monocyte
      recruitment, suggesting that monocytes recruited to the peritoneum originate in
      the spleen. These results suggest that noradrenergic neurons regulate the immune
      response through two pathways. First, sympathetic nerve-derived norepinephrine
      directly restrains MCP-1 production by peritoneal macrophages during infection.
      Second, norepinephrine derived from the vagally innervated splenic nerve
      regulates splenic monocyte egress. Removal of these two modulators of the immune
      response enhances antibacterial immunity and improves survival. These results may
      have implications for how states of catecholamine excess influence the host
      response to bacterial infections.

PMID- 23543757
TI  - Cutting edge: the pathogenicity of IFN-gamma-producing Th17 cells is independent
      of T-bet.
AB  - During the development of experimental autoimmune encephalomyelitis (EAE), the
      proportion of pathogenic and myelin-specific cells within CNS-infiltrating
      cytokine-producing Th cells is unknown. Using an IL-17A/IFN-gamma double reporter
      mouse and I-A(b)/myelin oligodendrocyte glycoprotein 38-49 tetramer, we show in
      this study that IL-17(+)IFN-gamma(+) Th cells, which are expanded in the CNS
      during EAE, are highly enriched in myelin oligodendrocyte glycoprotein-specific T
      cells. We further demonstrate that IL-23 is essential for the generation and
      expansion of IFN-gamma-producing Th17 cells independently of the Th1-associated
      transcription factors T-bet, STAT1, and STAT4. Furthermore, Th17 and IL-17(+)IFN
      gamma(+) Th cells can induce CNS autoimmunity independently of T-bet. Whereas T
      bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell-mediated
      autoimmunity. Our results suggest the existence of different epigenetic programs
      that regulate IFN-gamma expression in Th1 and Th17 cells.

PMID- 23543758
TI  - Differential binding of pyruvate dehydrogenase complex-E2 epitopes by DRB1*08:01
      and DRB1*11:01 Is predicted by their structural motifs and correlates with
      disease risk.
AB  - DRB1*08:01 (DR0801) and DRB1*11:01 (DR1101) are highly homologous alleles that
      have opposing effects on susceptibility to primary biliary cirrhosis (PBC).
      DR0801 confers risk and shares a key feature with other HLA class II alleles that
      predispose to autoimmunity: a nonaspartic acid at beta57. DR1101 is associated
      with protection from PBC, and its sequence includes an aspartic acid at beta57.
      To elucidate a mechanism for the opposing effects of these HLA alleles on PBC
      susceptibility, we compared the features of epitopes presented by DR0801 and
      DR1101. First, we identified DR0801- and DR1101-restricted epitopes within
      multiple viral Ags, observing both shared and distinct epitopes. Because DR0801
      is not well characterized, we deduced its motif by measuring binding affinities
      for a library of peptides, confirming its key features through structural
      modeling. DR0801 was distinct from DR1101 in its ability to accommodate charged
      residues within all but one of its binding pockets. In particular, DR0801
      strongly preferred acidic residues in pocket 9. These findings were used to
      identify potentially antigenic sequences within PDC-E2 (an important hepatic
      autoantigen) that contain a DR0801 motif. Four peptides bound to DR0801 with
      reasonable affinity, but only one of these bound to DR1101. Three peptides, PDC
      E2145-159, PDC-E2(249-263), and PDC-E2(629-643), elicited high-affinity T cell
      responses in DR0801 subjects, implicating these as likely autoreactive
      specificities. Therefore, the unique molecular features of DR0801 may lead to the
      selection of a distinct T cell repertoire that contributes to breakdown of self
      tolerance in primary biliary cirrhosis, whereas those of DR1101 promote
      tolerance.

PMID- 23543759
TI  - Cutting edge: allergen-specific CD4 T cells respond indirectly to thymic stromal
      lymphopoietin to promote allergic responses in the skin.
AB  - Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that has
      been implicated in the initiation of allergic responses. CD4 T cells and
      dendritic cells are able to respond to TSLP in vitro; however, there has not been
      a careful dissection of the spatiotemporal response to TSLP by CD4 T cells in
      vivo during an allergic response. Previous work has suggested a requirement for
      TSLP in amplifying Th2 responses during allergen challenge by direct action on
      CD4 T cells; however, these studies did not determine whether there is an effect
      of TSLP on CD4 T cells during allergen sensitization. In this study we
      demonstrate an indirect role for TSLP on CD4 T cells during sensitization and
      challenge phases of an allergic response. This indirect effect of TSLP on CD4 T
      cells is due in part to the presence of TSLP exclusively in the allergen
      sensitized and -challenged skin, rather than the draining lymph nodes.

PMID- 23543760
TI  - Cutting Edge: defective follicular exclusion of apoptotic antigens due to
      marginal zone macrophage defects in autoimmune BXD2 mice.
AB  - Marginal zone macrophages (MZMs) act as a barrier to entry of circulating
      apoptotic debris into the follicles of secondary lymphoid organs. In autoimmune
      BXD2 mice, there is a progressive reduction in the function and numbers of MZMs.
      Absence of MZMs results in retention of apoptotic cell (AC) debris within the
      marginal zone (MZ) and increased loading of AC Ags on MZ B cells and MZ-precursor
      (MZ-P) B cells. The MZ-P B cells are capable of translocating the AC Ags to the
      follicular zone and stimulating T cells. Both MZMs and MZ-P B cells from BXD2
      mice express low levels of tolerogenic signals and high levels of inflammatory
      signals. Thus, the current study suggests a multifaceted mechanism in which MZMs
      maintain tolerance to apoptotic autoantigens and suppress their translocation to
      follicles. Lack of clearance of apoptotic debris by MZMs drives follicular Ag
      transportation by MZ-P B cells to stimulate an autoimmune response.

PMID- 23543761
TI  - Cathepsin K is involved in development of psoriasis-like skin lesions through TLR
      dependent Th17 activation.
AB  - Cathepsins (CTSs) are lysosomal cysteine proteases that play an important role in
      the turnover of intracellular proteins and extracellular proteins, such as the
      degradation of extracellular matrices and the processing of antigenic proteins. A
      CTS inhibitor, NC-2300, not only suppresses bone erosion by inhibition of
      cathepsin K (CTSK), but also ameliorates paw swelling at inflamed joints in
      adjuvant-induced arthritis in rats. It has been demonstrated that the
      amelioration of joint inflammation by NC-2300 is mediated by the downregulation
      of cytokine expression in dendritic cells, which are essential for Th17
      activation. In this work, we studied the role for CTSs in the pathogenesis of
      psoriasis-like lesion in K5.Stat3C mice, a mouse model of psoriasis, in which
      Th17 contributes to lesion development similar to psoriasis. Psoriatic lesions
      expressed increased levels of Ctsk and Ctss mRNA compared with uninvolved skin
      and normal control skin. Similarly, the epidermis and dermis in K5.Stat3C mice
      demonstrated increased CTSK activities, which were sensitive to NC-2300. Topical
      treatment with NC-2300 significantly ameliorated 12-O-tetradecanoylphorbol-13
      acetate-induced psoriasis-like lesions in K5.Stat3C mice, and downregulated the
      expression of IL-12, IL-23, and Th17 cytokines. In vitro experiments revealed
      that TLR7 activation of bone marrow-derived myeloid dendritic cells led to
      increase in IL-23 at mRNA and protein levels, which were downregulated by NC
      2300. These results suggest that CTSK plays a role in development of psoriatic
      lesions through TLR7-dependent Th17 polarization.

PMID- 23543763
TI  - Comparison of standard and low dose intraoperative mitomycin C in prevention of
      corneal hazeafter photorefractive keratectomy.
AB  - BACKGROUND: This study aimed to compare two doses of Mitomycin C in reducing haze
      formation after photorefractive keratectomy. METHODS: 170 eyes of 85 patients
      enrolled; in each patient one eye randomly assigned to be treated by low dose
      intraoperative MMC (LDMMC) and other eye by standard dose MMC (SDMMC). Then the
      patients were followed up to 6 months and refraction, Uncorrected Distant Visual
      Acuity (UCDVA), Best Corrected Distant Visual Acuity (BCDVA) and haze formation
      submitted in each postoperative exam. RESULTS: The mean preoperative refraction
      in LDMMC eyes was -3.08 (SD 1.65) sphere and 0.92 (SD 0.88) cylinder. These
      values for SDMMC eyes were -3.25 (SD 1.80) sphere and 0.81 (SD 0.84) cylinder.
      Mean postoperative sphere in LDMMC group was -0.132 (SD 0.503) and -0.138 (SD
      0.484) in 3 and 6 months after PRK. These results was -0.041 (SD 0.501) and 
      0.076 (SD 0.489) for SDMMC group. Mean postoperative cylinder 3 and 6 month after
      PRK was 0.435 (SD 0.218) and 0.423 (SD 0.255). In LDMMC group and 0.435 (SD
      0.247) and 0.426 (SD 0.261) in SDMMC group. In third month 14 eyes in LDMMC group
      presented with grade 1 score of clinical haze. From these eyes only 2 still had
      this haze after 6 month. 7 eyes in SDMMC group had grade 1 clinical haze at third
      month- but no clinical haze was seen at the end of 6(th) month. CONCLUSION: The
      results of the two doses of Mitomycin C were not significant. We suggest to use
      the lower dose to reduce its side effects.

PMID- 23543764
TI  - Increased intraocular pressure after extensive conjunctival removal: a case
      report.
AB  - A 50-year-old woman, who had undergone extensive removal of conjunctiva on the
      right eye for cosmetic purposes at a local clinic 8 months prior to presentation,
      was referred for uncontrolled intraocular pressure (IOP) elevation (up to 38
      mmHg) despite maximal medical treatment. The superior and inferior conjunctival
      and episcleral vessels were severely engorged and the nasal and temporal bulbar
      conjunctival areas were covered with an avascular epithelium. Gonioscopic
      examination revealed an open angle with Schlemm's canal filled with blood to 360
      degrees in the right eye. Brain and orbital magnetic resonance imaging and
      angiography results were normal. With the maximum tolerable anti-glaucoma
      medications, the IOP gradually decreased to 25 mmHg over 4 months of treatment.
      Extensive removal of conjunctiva and Tenon's capsule, leaving bare sclera, may
      lead to an elevation of the episcleral venous pressure because intrascleral and
      episcleral veins may no longer drain properly due to a lack of connection to
      Tenon's capsule and the conjunctival vasculature. This rare case suggests one
      possible mechanism of secondary glaucoma following ocular surgery.

PMID- 23543762
TI  - Dissociation of endotoxin tolerance and differentiation of alternatively
      activated macrophages.
AB  - Endotoxin tolerance is a complex phenomenon characterized primarily by decreased
      production of proinflammatory cytokines, chemokines, and other inflammatory
      mediators, whereas the expression of other genes are induced or unchanged.
      Endotoxin tolerance is induced by prior exposure of murine macrophages/human
      monocytes, experimental animals, or people to TLR ligands. Although recent
      studies reported a possible relationship between endotoxin tolerance and
      differentiation of alternatively activated macrophages (AA-MPhis or M2), we show
      in this study that LPS pretreatment of IL-4Ralpha(-/-) and STAT6(-/-)
      macrophages, which fail to develop into AA-MPhis, resulted in tolerance of
      proinflammatory cytokines, as well as molecules and chemokines previously
      associated with AA-MPhis (e.g., arginase-1, mannose receptor, CCL2, CCL17, and
      CCL22). In contrast to LPS, wild-type (WT) MPhis pretreated with IL-4, the
      prototype inducer of AA-MPhis, did not induce endotoxin tolerance with respect to
      proinflammatory cytokines, AA-MPhi-associated chemokines, negative regulators, NF
      kappaB binding and subunit composition, and MAPKs; conversely, IL-13(-/-)
      macrophages were tolerized equivalently to WT MPhis by LPS pretreatment. Further,
      IL-4Ralpha deficiency did not affect the reversal of endotoxin tolerance exerted
      by the histone deacetylase inhibitor trichostatin A. Like WT mice, 100% of LPS
      tolerized IL-4Ralpha-deficient mice survived LPS + d-galactosamine-induced lethal
      toxicity and exhibited decreased serum levels of proinflammatory cytokines and AA
      MPhi-associated chemokines induced by LPS challenge compared with nontolerized
      mice. These data indicate that the signaling pathways leading to endotoxin
      tolerance and differentiation of AA-MPhis are dissociable.

PMID- 23543765
TI  - Neurochemical and neurobehavioral effects of low lead exposure on the developing
      brain.
AB  - Lead is found in small but appreciable quantities in air, soil drinking water and
      food. Exposure to such amounts of lead does not cause acute lead toxicity, but
      produces subtle effects, particularly in children. The CDC advocates "safe" or
      "acceptable" levels of blood lead up to 10 MUg/dl, while OSHA declares blood lead
      levels up to 40 MUg/dl as "safe" or "acceptable" in the occupationally exposed.
      The objective of the study was to see if blood levels considered "safe" can cause
      changes in the biogenic neurotransmitters in the developing brain which may cause
      neurobehavioral defects like hyperactivity and other cognitive disorders. Albino
      Wistar rats were divided into the control and lead-treated groups. The control
      group was given unleaded water, while the lead-treated group was fed with 50 ppm
      lead acetate in drinking water. On day 45 the animals were subjected to a passive
      avoidance test, their blood analysed for ZPP and lead. They were then sacrificed
      and the neurotransmitters-Norepinephrine (NE) and its metabolite
      methoxyhydroxyphenylglycol (MHPG) estimated in the brain areas associated with
      learning and memory-the frontal cortex, hippocampus and the striatum by HPLC-ECD.
      Our results showed significant increases in blood lead, NE and MHPG, while ZPP
      increase was insignificant. The rats showed neurobehavioral abnormalities as
      assessed by the passive avoidance test. We concluded that low blood levels of
      lead cannot be considered "safe" or "acceptable" as it causes neurotransmitter
      alterations. Increased NE turnover is implicated in hyperactivity disorders such
      as ADHD and Tourette syndrome.

PMID- 23543766
TI  - RAGE regulation and signaling in inflammation and beyond.
AB  - RAGE is a key molecule in the onset and sustainment of the inflammatory response.
      New studies indicate that RAGE might represent a new link between the innate and
      adaptive immune system. RAGE belongs to the superfamily of Ig cell-surface
      receptors and is expressed on all types of leukocytes promoting activation,
      migration, or maturation of the different cells. RAGE expression is prominent on
      the activated endothelium, where it mediates leukocyte adhesion and
      transmigration. Moreover, proinflammatory molecules released from the inflamed or
      injured vascular system induce migration and proliferation of SMCs. RAGE binds a
      large number of different ligands and is therefore considered as a PRR,
      recognizing a structural motif rather than a specific ligand. In this review, we
      summarize the current knowledge about the signaling pathways activated in the
      different cell types and discuss a potential activation mechanism of RAGE, as
      well as putative options for therapeutic intervention. 

PMID- 23543767
TI  - Ly6 family proteins in neutrophil biology.
AB  - The murine Ly6 complex was identified 35 years ago using antisera to lymphocytes.
      With advances in mAb development, molecular cloning, and genome sequencing, >20
      structurally related genes have been identified within this complex on chromosome
      15. All members of the Ly6 family and their human homologues share the highly
      conserved LU domain and most also possess a GPI anchor. Interestingly, many Ly6
      proteins are expressed in a lineage-specific fashion, and their expression often
      correlates with stages of differentiation. As a result, Ly6 proteins are
      frequently used as surface markers for leukocyte subset identification and
      targets for antibody-mediated depletion. Murine neutrophils display prominent
      surface expression of several Ly6 proteins, including Ly6B, Ly6C, and Ly6G.
      Although the physiology of most Ly6 proteins is not well understood, a role in
      neutrophil functions, such as migration, is recognized increasingly. In this
      review, we will provide an overview of the Ly6 complex and discuss, in detail,
      the specific Ly6 proteins implicated in neutrophil biology. 

PMID- 23543768
TI  - The roles of complement receptor 3 and Fcgamma receptors during Leishmania
      phagosome maturation.
AB  - Leishmania are intracellular parasites adapted to surviving in macrophages, whose
      primary function is elimination of invading pathogens. Leishmania entry into host
      cells is receptor-mediated. These parasites are able to engage multiple host cell
      surface receptors, including MR, TLRs, CR3, and FcgammaRs. Here, we investigated
      the role of CR3 and FcgammaR engagement on the maturation of Leishmania
      containing phagosomes using CD11b-/- and FcgammaR-/- macrophages, and assessing
      EEA1 and lysosome-associated proteins is necessary for the phagosome maturation
      delay, characteristic of Leishmania infection. Leishmania-containing phagosomes
      do not fuse with lyosomes until 5 h postinfection in WT mice. Phagolysosome
      fusion occurs by 1 h in CD11b and FcgammaR common chain KO macrophages, although
      receptor deficiency does not influence Leishmania entry or viability. We also
      investigated the influence of serum components and their effects on phagosome
      maturation progression. Opsonization with normal mouse serum, complement
      deficient serum, or serum from Leishmania-infected mice all influenced phagosome
      maturation progression. Our results indicate that opsonophagocytosis influences
      phagosomal trafficking of Leishmania without altering the intracellular fate.

PMID- 23543769
TI  - IL-4Ralpha on CD4+ T cells plays a pathogenic role in respiratory syncytial virus
      reinfection in mice infected initially as neonates.
AB  - RSV is the major cause of severe bronchiolitis in infants, and severe
      bronchiolitis as a result of RSV is associated with subsequent asthma
      development. A biased Th2 immune response is thought to be responsible for
      neonatal RSV pathogenesis; however, molecular mechanisms remain elusive. Our data
      demonstrate, for the first time, that IL-4Ralpha is up-regulated in vitro on
      human CD4(+) T cells from cord blood following RSV stimulation and in vivo on
      mouse pulmonary CD4(+) T cells upon reinfection of mice, initially infected as
      neonates. Th cell-specific deletion of Il4ra attenuated Th2 responses and
      abolished the immunopathophysiology upon reinfection, including airway hyper
      reactivity, eosinophilia, and mucus hyperproduction in mice infected initially as
      neonates. These findings support a pathogenic role for IL-4Ralpha on Th cells
      following RSV reinfection of mice initially infected as neonates; more
      importantly, our data from human cells suggest that the same mechanism occurs in
      humans.

PMID- 23543770
TI  - Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive
      to arachidonic acid and docosahexaenoic acid intake in growing piglets.
AB  - The dose-responsiveness of plasma oxylipins to incremental dietary intake of
      arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was
      determined in piglets. Piglets randomly received one of six formulas (n = 8 per
      group) from days 3 to 27 postnatally. Diets contained incremental ARA or
      incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.1/1.0; (A2)
      0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D1) 0.66/0.33; and (D2) 0.67/0.62,
      resulting in incremental intake (g/kg BW/day) of ARA: 0.07 +/- 0.01, 0.43 +/-
      0.03, 0.55 +/- 0.03, and 0.82 +/- 0.05 at constant DHA intake (0.82 +/- 0.05), or
      incremental intake of DHA: 0.27 +/- 0.02, 0.49 +/- 0.03, and 0.81 +/- 0.05 at
      constant ARA intake (0.54 +/- 0.04). Plasma oxylipin concentrations and free
      plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary
      ARA intake dose-dependently increased plasma ARA levels. In parallel, ARA intake
      dose-dependently increased ARA-derived diols 5,6- and 14,15
      dihydroxyeicosatrienoic acid (DiHETrE) and linoleic acid-derived 12,13
      dihydroxyoctadecenoic acid (DiHOME), downstream metabolites of cytochrome P450
      expoxygenase (CYP). The ARA epoxide products from CYP are important in vascular
      homeostatic maintenance. Incremental DHA intake increased plasma DHA and most
      markedly raised the eicosapentaenoic acid (EPA) metabolite 17,18
      dihydroxyeicosatetraenoic acid (DiHETE) and the DHA metabolite 19,20
      dihydroxydocosapentaenoic acid (DiHDPE). In conclusion, increasing ARA and DHA
      intake dose-dependently influenced endogenous n-6 and n-3 oxylipin plasma
      concentrations in growing piglets, although the biological relevance of these
      findings remains to be determined.

PMID- 23543771
TI  - Soil moisture effects on the activity of three entomopathogenic nematodes
      (Steinernematidae and Heterorhabditidae) isolated from Meghalaya, India.
AB  - Entomopathogenic nematodes (EPNs) are obligate parasites of insects that are
      widely distributed in soils throughout the world. They have great potential for
      use as biological control agents for insect pests. It is known that strains of
      Steinernema and Heterorhabditis isolated from different geographical regions
      exhibit differences in their ecological traits, such as infectivity,
      establishment, survival, reproduction, etc. A precise knowledge of these factors
      is therefore an essential pre-requisite for devising successful strategies to use
      these nematodes in biological control programmes. The present study investigated
      the effect of soil moisture on the activity (as measured by number of nematodes
      established in hosts) of three entomopathogenic nematode species (Heterorhabditis
      indica Poinar, Karunakar & David; Steinernema thermophilum Ganguly & Singh;
      Steinernema glaseri Steiner), isolated from forest soils in Meghalaya, India,
      under laboratory conditions. The experiments for EPNs were conducted at 25 +/- 2
      degrees C (30 +/- 2 degrees C for S. thermophilum) in a sandy loam soil (85%
      sand, 12% silt and 3% clay, pH 6.54). Last instar larvae of wax moth, Galleria
      mellonella served as the experimental insect host. The soil moistures tested were
      3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 25% (w/w). The study revealed that
      soil moisture has marked influences on establishment of infective juveniles of
      different nematode species in insect host. While, S. thermophilum showed
      establishment at 4% and above soil moistures, H. indica and S. glaseri showed
      establishment at 5% and above soil moistures. The optimum soil moisture for
      different nematode species were noted as: H. indica 8-18%, S. thermophilum 6-20%,
      and S. glaseri 8-25%. Further, a minimum of 6% soil moisture was noted to be
      essential for achieving 100% host mortality for all the three nematode species.

PMID- 23543773
TI  - Differentiating the wild from the attenuated during a measles outbreak.
AB  - In the midst of a local measles outbreak, a recently immunized child was
      investigated for a new-onset measles-type rash. Nucleic acid testing identified
      that a vaccine-type measles virus was being shed in the urine. Clinically
      differentiating measles from a nonmeasles rash is challenging, but can be
      supported by a thorough medical history evaluation. Rashes are expected to occur
      after immunization; nucleic acid testing can be used when it is difficult to
      differentiate between wild and attenuated strains.

PMID- 23543774
TI  - Fat body, hemolymph and ovary routes for delivery of substances to ovary in
      Melipona quadrifasciata anthidioides: differences among castes through the use of
      electron-opaque tracers.
AB  - The yolk protein precursor, vitellogenin (Vg), in bees is synthesized in the fat
      body trophocytes, delivered to the hemolymph and ultimately absorbed from there
      during the vitellogenic phase of oocytes in the active ovary. The routes tracing
      the material exchange that occurs between the trophocytes and the hemolymph, in
      addition to the transportation from the hemolymph to the ovarian follicles, were
      marked by alkaline phosphatase and lanthanum nitrate (LN). Active ovaries from
      nurse workers and physogastric queens, as well as inactive ovaries of virgin
      queens, were examined by transmission electron microscopy. The LN permitted
      better visualization of the routes of exchanges between the organs and the
      hemolymph. Both methods demonstrate the apparent differences between the phases
      of the ovary and the bee caste. In inactive ovaries of the virgin queens, the
      routes from the follicular epithelium to the oocyte remain closed; conversely,
      they are open in active ovaries of the nurse workers and physogastric queens. The
      differences between the methods and classes of bees are discussed. 

PMID- 23543772
TI  - Unraveling the complexities of the HDL lipidome.
AB  - Plasma high density lipoproteins (HDL) are small, dense, protein-rich particles
      compared with other lipoprotein classes; roughly half of total HDL mass is
      accounted for by lipid components. Phospholipids predominate in the HDL lipidome,
      accounting for 40-60% of total lipid, with lesser proportions of cholesteryl
      esters (30-40%), triglycerides (5-12%), and free cholesterol (5-10%). Lipidomic
      approaches have provided initial insights into the HDL lipidome with
      identification of over 200 individual molecular lipids species in normolipidemic
      HDL. Plasma HDL particles, however, reveal high levels of structural,
      compositional, and functional heterogeneity. Establishing direct relationships
      between HDL structure, composition, and atheroprotective functions bears the
      potential to identify clinically relevant HDL subpopulations. Furthermore,
      development of HDL-based therapies designed to target beneficial subspecies
      within the circulating HDL pool can be facilitated using this approach. HDL
      lipidomics can equally contribute to the identification of biomarkers of both
      normal and deficient HDL functionality, which may prove useful as biomarkers of
      cardiovascular risk. However, numerous technical issues remain to be addressed in
      order to make such developments possible. With all technical questions resolved,
      quantitative analysis of the molecular components of the HDL lipidome will
      contribute to expand our knowledge of cardiovascular and metabolic diseases. 

PMID- 23543776
TI  - Increasing antimicrobial resistance of campylobacter jejuni isolated from
      paediatric diarrhea cases in a tertiary care hospital of new delhi, India.
AB  - INTRODUCTION: The resistance to the clinically important antimicrobial agents,
      particularly the fluoroquinolones and the macrolides, is increasing among the
      Campylobacter isolates. Only limited data is available regarding the changing
      antimicrobial resistance pattern in the Indian scenario. METHODOLOGY: Three
      hundred fifty cases (ages <=12years) of acute diarrhoea, who were admitted to a
      tertiary-care hospital, were investigated for Campylobacter spp. The
      antimicrobial susceptibilities of all the C. jejuni isolates were assessed by the
      disk diffusion method according to the CLSI guidelines. RESULTS: A total of 36
      isolates of C. jejuni were tested for their antimicrobial susceptibilities. A
      high degree of resistance to the fluoroquinolones (100% to Nalidixic acid and
      86.66% to Ciprofloxacin) was detected in the Campylobacter isolates. The
      frequency of resistance against Tetracycline was 33.33% and that against
      Erythromycin was 22.2%. Fifteen (41.66%) isolates were multiresistant, being
      resistant to 3 or more antimicrobial agents. CONCLUSIONS: An increased resistance
      to the quinolones and the macrolides and multidrug resistance warrant a
      reconsideration of their use as the drugs of choice in patients with severe
      gastroenteritis when Campylobacter is the presumed cause.

PMID- 23543775
TI  - Dopamine Genetics and Function in Food and Substance Abuse.
AB  - Having entered the genomics era with confidence in the future of medicine,
      including psychiatry, identifying the role of DNA and polymorphic associations
      with brain reward circuitry has led to a new understanding of all addictive
      behaviors. It is noteworthy that this strategy may provide treatment for the
      millions who are the victims of "Reward Deficiency Syndrome" (RDS) a genetic
      disorder of brain reward circuitry. This article will focus on drugs and food
      being mutuality addictive, and the role of dopamine genetics and function in
      addictions, including the interaction of the dopamine transporter, and sodium
      food. We will briefly review our concept that concerns the genetic antecedents of
      multiple-addictions (RDS). Studies have also shown that evaluating a panel of
      established reward genes and polymorphisms enables the stratification of genetic
      risk to RDS. The panel is called the "Genetic Addiction Risk Score (GARS)", and
      is a tool for the diagnosis of a genetic predisposition for RDS. The use of this
      test, as pointed out by others, would benefit the medical community by
      identifying at risk individuals at a very early age. We encourage, in depth work
      in both animal and human models of addiction. We encourage further exploration of
      the neurogenetic correlates of the commonalities between food and drug addiction
      and endorse forward thinking hypotheses like "The Salted Food Addiction
      Hypothesis".

PMID- 23543777
TI  - Rapid discrimination between Anopheles gambiae s.s. and Anopheles arabiensis by
      High-Resolution Melt (HRM) analysis.
AB  - There is a need for more cost-effective options to more accurately discriminate
      among members of the Anopheles gambiae complex, particularly An. gambiae and
      Anopheles arabiensis. These species are morphologically indistinguishable in the
      adult stage, have overlapping distributions, but are behaviorally and
      ecologically different, yet both are efficient vectors of malaria in equatorial
      Africa. The method described here, High-Resolution Melt (HRM) analysis, takes
      advantage of minute differences in DNA melting characteristics, depending on the
      number of incongruent single nucleotide polymorphisms in an intragenic spacer
      region of the X-chromosome-based ribosomal DNA. The two species in question
      differ by an average of 13 single-nucleotide polymorphisms giving widely
      divergent melting curves. A real-time PCR system, Bio-Rad CFX96, was used in
      combination with a dsDNA-specific dye, EvaGreen, to detect and measure the
      melting properties of the amplicon generated from leg-extracted DNA of selected
      mosquitoes. Results with seven individuals from pure colonies of known species,
      as well as 10 field-captured individuals unambiguously identified by DNA
      sequencing, demonstrated that the method provided a high level of accuracy. The
      method was used to identify 86 field mosquitoes through the assignment of each to
      the two common clusters with a high degree of certainty. Each cluster was defined
      by individuals from pure colonies. HRM analysis is simpler to use than most other
      methods and provides comparable or more accurate discrimination between the two
      sibling species but requires a specialized melt-analysis instrument and software.

PMID- 23543778
TI  - Synchronous jejunal gastrointestinal stromal tumor and primary adenocarcinoma of
      the colon.
AB  - Synchronous gastrointestinal stromal tumors (GIST) and primary epithelial cancers
      of the gastrointestinal tract is an uncommon occurrence. We report a case of
      jejunal GIST which was detected incidentally in a patient during surgery for
      carcinoma of the sigmoid colon. The uncommon association of such synchronous
      tumors prompts a search for a common molecular pathway for carcinogenesis in
      gastrointestinal epithelial and stromal tumors.

PMID- 23543780
TI  - The effect of estrogen plus progestin hormone therapy on breast cancer mortality:
      still unresolved.

PMID- 23543779
TI  - Estrogen plus progestin and breast cancer incidence and mortality in the Women's
      Health Initiative Observational Study.
AB  - BACKGROUND: In the Women's Health Initiative (WHI) randomized trial, estrogen
      plus progestin increased both breast cancer incidence and mortality. In contrast,
      most observational studies associate estrogen plus progestin with favorable
      prognosis breast cancers. To address differences, a cohort of WHI observational
      study participants with characteristics similar to the WHI clinical trial was
      studied. METHODS: We identified 41 449 postmenopausal women with no prior
      hysterectomy and mammogram negative within 2 years who were either not hormone
      users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable
      adjusted Cox proportional hazard regression was used to calculate hazard ratios
      (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.
      RESULTS: After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers,
      incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs
      0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P <
      .001). Women initiating hormone therapy closer to menopause had higher breast
      cancer risk with linear diminishing influence as time from menopause increased (P
      < .001). Survival after breast cancer, measured from diagnosis, was similar in
      combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35).
      On a population basis, there were somewhat more deaths from breast cancer,
      measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more
      all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001)
      in estrogen plus progestin users than in nonusers. CONCLUSIONS: Consistent with
      WHI randomized trial findings, estrogen plus progestin use is associated with
      increased breast cancer incidence. Because prognosis after diagnosis on combined
      hormone therapy is similar to that of nonusers, increased breast cancer mortality
      can be expected.

PMID- 23543781
TI  - Visual task enhances spatial selectivity in the human auditory cortex.
AB  - The auditory cortex represents spatial locations differently from other sensory
      modalities. While visual and tactile cortices utilize topographical space maps,
      for audition no such cortical map has been found. Instead, auditory cortical
      neurons have wide spatial receptive fields and together they form a population
      rate code of sound source location. Recent studies have shown that this code is
      modulated by task conditions so that during auditory tasks it provides better
      selectivity to sound source location than during idle listening. The goal of this
      study was to establish whether the neural representation of auditory space can
      also be influenced by task conditions involving other sensory modalities than
      hearing. Therefore, we conducted magnetoencephalography (MEG) recordings in which
      auditory spatial selectivity of the human cortex was probed with an adaptation
      paradigm while subjects performed a visual task. Engaging in the task led to an
      increase in neural selectivity to sound source location compared to when no task
      was performed. This suggests that an enhancement in the population rate code of
      auditory space took place during task performance. This enhancement in auditory
      spatial selectivity was independent of the direction of visual orientation.
      Together with previous studies, these findings suggest that performing any
      demanding task, even one in which sounds and their source locations are
      irrelevant, can lead to enhancements in the neural representation of auditory
      space. Such mechanisms may have great survival value as sounds are capable of
      producing location information on potentially relevant events in all directions
      and over long distances.

PMID- 23543782
TI  - Diversity of endophytic fungi from roots of Panax ginseng and their saponin yield
      capacities.
AB  - Endophytes of medicinal plants have the capacity to synthesis same or similar
      active substances with their hosts. To investigate the diversity and capacity to
      produce saponins of endophytic fungi of Panax ginseng, thirty-eight strains of
      were isolated. Polymerase chain reaction (PCR) and sequencing were used to
      identify the isolates, and saponins concentrations in the cultures were measured.
      Agar diffusion method was used to test antimicrobial activity. High-performance
      liquid chromatography (HPLC) was used to analyze ginsenosides produced by
      representative strains. Nectria, Aspergillus, Fusarium, Verticillium,
      Engyodontium, Plectosphaerella, Penicillium, Cladosporium, and Ascomycete species
      were isolated. Overall, 18.4% of the isolates belonged to Nectria (Nectria
      haematococca), 13.2% belonged to Aspergillus, and 10.5% belonged to Penicillium.
      The highest concentration of triterpenoid saponin was 0.181 mg/ml (Pg27),
      followed by 0.144 mg/ml (Pg30 and Pg42-1). According to the results of the
      phylogenetic results, these isolates were species of Fusarium, Aspergillus and
      Verticillium, respectively. The culture filtrate of Pg30 exhibited its
      antibacterial activity Staphylococcus aureus. Pg 27 and Pg30 could excrete the
      substances to inhibit the growth of Rhizoctonia solani. Pg42-1 showed strong
      inhibition against Klebsiella pneumoniae. From HPLC results, the ginsenoside Rb2
      was detected in both Pg27 and Pg30 cultures. The ginsenoside Rc was found in Pg42
      1 cultures. In conclusion, thirty-eight endophytic fungal strains were isolated
      and Pg27 (Fusarium sp.) has a potential application value in saponins production.

PMID- 23543783
TI  - Vitamin d deficiency among postmenopausal women with osteoporosis.
AB  - BACKGROUND: Hypovitaminosis D is widely prevalent in India and is a formidable
      issue especially in postmenopausal women. The study intends to estimate the
      prevalence of vitamin D deficiency among postmenopausal women with osteoporosis.
      METHODS: The study was performed at a referral teaching institute in north India
      between 2007 and 2009. One hundred and ninety postmenopausal osteoporotic women
      were enrolled and the clinical information was collected along with the
      assessment of biochemical parameters. RESULTS & CONCLUSION: Serum vitamin D was
      found to be de- ficient in two third of patients. A significant correlation was
      observed between body mass index and bone mineral density at lumbar spine.
      Prevention and early detection of hypovitaminosis D is the key to reduce the
      incidence of osteoporosis among postmenopausal women.

PMID- 23543784
TI  - Interlocking feedback loops govern the dynamic behavior of the floral transition
      in Arabidopsis.
AB  - During flowering, primordia on the flanks of the shoot apical meristem are
      specified to form flowers instead of leaves. Like many plants, Arabidopsis
      thaliana integrates environmental and endogenous signals to control the timing of
      reproduction. To study the underlying regulatory logic of the floral transition,
      we used a combination of modeling and experiments to define a core gene
      regulatory network. We show that FLOWERING LOCUS T (FT) and TERMINAL FLOWER1
      (TFL1) act through FD and FD PARALOG to regulate the transition. The major floral
      meristem identity gene LEAFY (LFY) directly activates FD, creating a positive
      feedback loop. This network predicts flowering behavior for different genotypes
      and displays key properties of the floral transition, such as signal integration
      and irreversibility. Furthermore, modeling suggests that the control of TFL1 is
      important to flexibly counterbalance incoming FT signals, allowing a pool of
      undifferentiated cells to be maintained despite strong differentiation signals in
      nearby cells. This regulatory system requires TFL1 expression to rise in
      proportion to the strength of the floral inductive signal. In this network, low
      initial levels of LFY or TFL1 expression are sufficient to tip the system into
      either a stable flowering or vegetative state upon floral induction.

PMID- 23543786
TI  - The linear stochastic order and directed inference for multivariate ordered
      distributions.
AB  - Researchers are often interested in drawing inferences regarding the order
      between two experimental groups on the basis of multivariate response data. Since
      standard multivariate methods are designed for two sided alternatives they may
      not be ideal for testing for order between two groups. In this article we
      introduce the notion of the linear stochastic order and investigate its
      properties. Statistical theory and methodology are developed to both estimate the
      direction which best separates two arbitrary ordered distributions and to test
      for order between the two groups. The new methodology generalizes Roy's classical
      largest root test to the nonparametric setting and is applicable to random
      vectors with discrete and/or continuous components. The proposed methodology is
      illustrated using data obtained from a 90-day pre-chronic rodent cancer bioassay
      study conducted by the National Toxicology Program (NTP).

PMID- 23543785
TI  - Roles of N-terminal fatty acid acylations in membrane compartment partitioning:
      Arabidopsis h-type thioredoxins as a case study.
AB  - N-terminal fatty acylations (N-myristoylation [MYR] and S-palmitoylation [PAL])
      are crucial modifications affecting 2 to 4% of eukaryotic proteins. The role of
      these modifications is to target proteins to membranes. Predictive tools have
      revealed unexpected targets of these acylations in Arabidopsis thaliana and other
      plants. However, little is known about how N-terminal lipidation governs membrane
      compartmentalization of proteins in plants. We show here that h-type thioredoxins
      (h-TRXs) cluster in four evolutionary subgroups displaying strictly conserved N
      terminal modifications. It was predicted that one subgroup undergoes only MYR and
      another undergoes both MYR and PAL. We used plant TRXs as a model protein family
      to explore the effect of MYR alone or MYR and PAL in the same family of proteins.
      We used a high-throughput biochemical strategy to assess MYR of specific TRXs.
      Moreover, various TRX-green fluorescent protein fusions revealed that MYR
      localized protein to the endomembrane system and that partitioning between this
      membrane compartment and the cytosol correlated with the catalytic efficiency of
      the N-myristoyltransferase acting at the N terminus of the TRXs. Generalization
      of these results was obtained using several randomly selected Arabidopsis
      proteins displaying a MYR site only. Finally, we demonstrated that a
      palmitoylatable Cys residue flanking the MYR site is crucial to localize proteins
      to micropatching zones of the plasma membrane.

PMID- 23543787
TI  - Insulin sensitizing effect of 3 Indian medicinal plants: an in vitro study.
AB  - OBJECTIVE: Measurement of glucose uptake into peripheral tissue is an important
      mechanism to assess Insulin sensitivity. The present in vitro study was conducted
      to evaluate the Insulin sensitizing activity of Phyllanthus emblica (Pe),
      Tinospora cordifolia (Tc) and Curcuma longa (Cl) by assessing glucose uptake
      activity in a 3T3L1 adipocyte model. MATERIALS AND METHODS: The 3T3 L1 fibroblast
      cells were differentiated to adipocytes, using a cocktail of insulin, isobutyl-1
      methylxanthine and dexamethazone. These adipocytes were initially treated with
      different concentrations of the selected plants following which 2-deoxy glucose
      uptake was estimated using a radioactive assay. The effects of plants on glucose
      uptake both in the presence and absence of insulin was evaluated and compared
      with pioglitazone, a known insulin sensitizer. RESULTS: Pe and Tc per se
      significantly stimulated glucose uptake in 3T3-L1 adipocytes in a dose dependent
      manner with maximal effect at higher concentrations (200 MUg/ml). The effect of
      both Pe and Tc at 200 MUg/ml was comparable to insulin and greater than
      pioglitazone. Cl per se stimulated glucose uptake with maximal effect at 50
      MUg/ml. However, this effect was lesser as compared to insulin with higher
      concentrations inhibiting glucose uptake. When combined with insulin, an
      antagonist effect was observed between Pe, Tc and insulin indicating a possible
      plant-drug interaction while Cl in combination with insulin showed an increase in
      the glucose uptake as compared to Cl alone. CONCLUSION: The results suggest that
      one of the mechanisms for the anti-diabetic effect of Pe, Cl and Tc may be
      through an insulin sensitizing effect (stimulation of glucose uptake into
      adipocytes). Further studies using other target sites viz. skeletal muscle and
      hepatocytes models and in an insulin resistant state would help substantiate this
      conclusion.

PMID- 23543788
TI  - The pathology of lithium induced nephropathy: a case report and review, with
      emphasis on the demonstration of mast cells.
AB  - Lithium is a psychotropic agent which is widely employed in the psychiatric
      practice throughout the world. The therapeutic index of lithium is low and an
      acute intoxication may appear, which may lead to death or a permanent disability.
      A frequent side effect of lithium is renal toxicity. The collecting tubules have
      been identified as the site of action of lithium, due to the down regulation of
      Acquaporin-2. The mast cells have been associated with a wide range of human
      renal diseases. They have been documented to be associated with interstitial
      fibrosis and an impaired renal function. We are reporting a case of a 42 year old
      male who was admitted with a history of an altered sensorium of short duration.
      He had bipolar disorder and was on lithium. Investigations revealed a severely
      compromised renal function. The patient's condition worsened and he expired. A
      necropsy was performed. The kidneys and the lungs were subjected to a
      histopathological examination. The kidneys showed a significant Chronic
      Tubulointerstitial Nephropathy [CTIN] and a considerable glomerular pathology.
      Toludine blue [1%] staining demonstrated mast cells in the interstitium and the
      connective tissue of the renal pelvis. This appears to be the first time that
      mast cells were demonstrated in a case of lithium induced nephropathy in humans.
      It may be hypothesized that mast cells may possibly play a role in lithium
      induced nephropathy as a concurrent mechanism.

PMID- 23543789
TI  - Multilanthanide Systems for Medical Imaging Applications.
AB  - Molecules containing multiple lanthanide ions have unique potential in
      applications for medical imaging including the areas of magnetic resonance
      imaging (MRI) and fluoresence imaging. The study of multilanthanide complexes as
      contrast agents for MRI and as biologically responsive fluorescent probes has
      resulted in an improved understanding of the structural characteristics that
      govern the behavior of these complexes. This review will survey the last five
      years of progress in multinuclear lanthanide complexes with a specific focus on
      the structural parameters that impact potential medical imaging applications. The
      patents cited in this review are from the last five years and describe contrast
      agents that contain multiple lanthanide ions.

PMID- 23543790
TI  - Predictors of Accessing Substance Abuse Services Among Individuals With Mental
      Disorders Released From Correctional Custody.
AB  - OBJECTIVE: In the context of an increasing correctional population and
      corresponding rates of mental illness and substance abuse among this population,
      this study focuses on describing the predictors of substance abuse service
      utilization for ex-inmates with dual disorders. Our aim is to assess the
      likelihood and characteristics of ex-inmates with mental disorders who access
      substance abuse treatment services within two years of correctional release.
      METHODS: Using merged administrative data on all ex-inmates with open mental
      health cases released from Massachusetts Department of Corrections and two County
      Houses of Corrections from 2007 to 2009 (N=2,280) and substance abuse treatment
      outcome data through 2011, we analyze the influence of demographics, behavioral
      and mental disorders, and criminal justice variables on entry into substance
      abuse treatment within 24 months post release. We also describe primary drug use
      and services utilized for all the ex-inmates who accessed substance abuse
      services (N=1,383). Regression techniques were used to analyze the probability of
      utilizing substance abuse treatment services by various demographic, behavioral,
      and criminal involvement characteristics. RESULTS: The prevalence of a history of
      substance use disorders is high in this population (69%; n = 1,285).
      Subsequently, at 24 months post release 61% (n = 1,383) of ex-inmates with open
      mental health cases utilized substance abuse treatment services. This group was
      disproportionately female, with a preincarceration history of substance abuse, an
      increased number of previous incarcerations, and more likely released under
      correctional supervision. CONCLUSIONS: Substance abuse is a chronic relapsing
      disorder and dual diagnosis is common among individuals with mental disorders
      involved with the criminal justice system. Their service needs and contacts
      across substance abuse, mental health, and criminal justice systems highlight
      individuals caught up in the institutional circuit. Study results point to the
      need for expanded and targeted dual diagnosis treatment approaches and relapse
      prevention for ex-inmates with mental disorders post correctional release.

PMID- 23543791
TI  - Race and Ethnicity, Religion Involvement, Church-based Social Support and
      Subjective Health in United States: A Case of Moderated Mediation.
AB  - BACKGROUND: To test if social support and ethnicity mediate/moderate the
      association between religion involvement and subjective health in the United
      States. METHODS: This is a secondary analysis of National Survey of American
      Life, 2003. Hierarchical regression was fit to a national household probability
      sample of adult African Americans (n = 3570), Caribbean Blacks (n = 1621), and
      Whites (n = 891). Frequency of church attendance, positive/negative church-based
      social support, ethnicity, and subjective health (overall life satisfaction and
      self-rated mental health) were considered as predictor, mediator, moderator and
      outcome, respectively. RESULTS: Frequency of church attendance had a significant
      and positive association with mental health and life satisfaction among all
      ethnic groups. Frequency of church attendance was also correlated with positive
      and negative social support among all ethnic groups. Church-based social support
      fully mediated the association between frequency of church attendance and overall
      life satisfaction among African Americans but not among Caribbean Blacks, or
      Whites. Church-based social support, however, partially mediated the association
      between frequency of church attendance and overall mental health among African
      Americans but not among Caribbean Blacks or Whites. CONCLUSION: Ethnicity shapes
      how church-based social support mediates the association between religious
      involvement and subjective health. Our results showed a moderating mediation
      effect of ethnicity and social support on the religious involvement-subjective
      health linkage, in a way that it is only among African Americans that social
      support is a pathway for the beneficial health effect of religious involvement.

PMID- 23543792
TI  - Safe excision of a large overhanging cystic bleb following autologous blood
      injection and compression suture.
AB  - Here, we report a large, overhanging cystic bleb that compromised vision and
      induced a foreign body sensation in a patient who underwent a trabeculectomy
      surgery with anti-metabolite therapy 4 years prior. Ultrasound biomicroscopy
      revealed multiple loculations with thin septa inside the bleb and a high risk of
      damage to the bleb was anticipated with a straight forward surgical excision. We
      injected autologous blood and placed a compression suture 6 weeks prior to
      surgical excision of the overhanging portion of the bleb. The operation was
      successful in preserving excellent bleb function, restoring visual acuity, and
      alleviating symptoms in our patient with up to 9 months of follow-up.

PMID- 23543793
TI  - Co-inheritance of HbD (Iran)/Beta Thalassemia IVS1-5 (G > C) Trait in a Punjabi
      Lady with Diabetes.
AB  - The present report describes the molecular study of HbD (Iran) (beta) 22 Glu ->
      Gln associated with beta-Thalassemia IVS1-5 (G > C) found in India, and the first
      case in which mutation has been identified using mass spectrometry. Given the
      apparent ethnic origin and the mobility of the variant hemoglobin at alkaline pH,
      hemoglobin D-Punjab would be suspected, but HPLC excluded this possibility.
      Further characterization of hemoglobinopathy was made by using nondenaturing gel
      electrophoresis and matrix assisted laser desorption ionization mass spectrometry
      and IVS1-5 being validated by reverse dot blot hybridization followed by
      sequencing of the beta-globin gene.

PMID- 23543795
TI  - Filariasis in an infant with B-cell acute lymphoblastic leukemia: a rare enigma.
AB  - Filariasis, a tropical parasitic infection, is a common public health problem in
      the Indian sub-continent. Occurrence of filariasis with acute lymphoblastic
      leukemia (ALL) is unusual, particularly in infants, since filariasis has a long
      incubation period of about 1 year. Though, there are case reports of
      leishmaniasis, malaria and other vector borne diseases seen in association with
      leukemias, filariasis co-existing with ALL has not been documented to the best of
      our knowledge. We report an incidental finding of Bancroftian filariasis in an 11
      month old female already diagnosed as B-cell ALL.

PMID- 23543796
TI  - Commentary: Getting to compliance. Multisector dialogue, collaboration and the
      International Code of Marketing of Breast Milk Substitutes.

PMID- 23543794
TI  - TDP-43 frontotemporal lobar degeneration and autoimmune disease.
AB  - BACKGROUND: The aetiology and pathogenesis of non-genetic forms of frontotemporal
      dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis
      remains elusive. Given the association between systemic inflammation and other
      neurodegenerative processes, links between autoimmunity and FTD need to be
      explored. OBJECTIVE: To describe the prevalence of systemic autoimmune disease in
      semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in
      progranulin (PGRN) mutation carriers compared with neurologically healthy normal
      controls (NC) and Alzheimer's disease (AD) as dementia controls. DESIGN: Case
      control. SETTING: Academic medical centres. PARTICIPANTS: 129 svPPA, 39 PGRN, 186
      NC and 158 AD patients underwent chart review for autoimmune conditions. A large
      subset of svPPA, PGRN and NC cohorts underwent serum analysis for tumour necrosis
      factor alpha (TNF-alpha) levels. OUTCOME MEASURES: chi(2) Comparison of
      autoimmune prevalence and follow-up logistic regression. RESULTS: There was a
      significantly increased risk of autoimmune disorders clustered around
      inflammatory arthritides, cutaneous disorders and gastrointestinal conditions in
      the svPPA and PGRN cohorts. Elevated TNF-alpha levels were observed in svPPA and
      PGRN compared with NC. CONCLUSIONS: svPPA and PGRN are associated with increased
      prevalence of specific and related autoimmune diseases compared with NC and AD.
      These findings suggest a unique pattern of systemic inflammation in svPPA and
      PGRN and open new research avenues for understanding and treating disorders
      associated with underlying transactive response DNA-binding protein 43
      aggregation.

PMID- 23543797
TI  - A new concept for classifying skull base defects for reconstructive surgery.
AB  - To classify the defects of the skull base, we present a new concept that is
      intuitive, simple to use, and consistent with subsequent reconstructive
      procedures. The centers of defects are determined in the anterior (I) or middle
      (II) skull base. The defects are classified as localized in the defect's center
      (Ia, IIa) or extended horizontally (Ib, IIb) or vertically (Ic, IIc) from the
      defect's center. Accompanying defects of the orbital contents and skin are
      indicated by "O" and "S," respectively. An algorithm for selecting subsequent
      reconstructive procedures was based on the classification. Using the new system,
      we retrospectively reclassified 90 skull base defects and examined how the defect
      classifications were related to the reconstructive flaps used and postoperative
      complications. All defects were reclassified with the new system without
      difficulty or omission. The mean correlation rate was high (88%) between the
      flaps indicated by the new classification and the flaps that had actually been
      used. The rate of postoperative complications tended to be higher with Ia, Ic,
      and IIb defects and combined defects. Our new classification concept can be used
      to classify defects and to help select flaps used for subsequent reconstructive
      procedures.

PMID- 23543798
TI  - The emerging role of high-dose-rate (HDR) brachytherapy as monotherapy for
      prostate cancer.
AB  - High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new
      brachytherapy procedure for prostate cancer. In addition to the intrinsic
      advantages of brachytherapy, including radiation dose concentration to the tumor
      and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can
      yield a more homogeneous and conformal dose distribution through image-based
      decisions for source dwell positions and by optimization of individual source
      dwell times. Indication can be extended even to T3a/b or a part of T4 tumors
      because the applicators can be positioned at the extracapsular lesion, into the
      seminal vesicles, and/or into the bladder, without any risk of source migration
      or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter
      /intra-fraction organ motion is not problematic. However, HDR monotherapy
      requires patients to stay in bed for 1-4 days during hospitalization, even though
      the actual overall treatment time is short. Recent findings that the alpha/beta
      value for prostate cancer is less than that for the surrounding late-responding
      normal tissue has made hypofractionation attractive, and HDR monotherapy can
      maximize this advantage of hypofractionation. Research on HDR monotherapy is
      accelerating, with a growing number of publications reporting excellent
      preliminary clinical results due to the high 'biologically effective dose (BED)'
      of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model
      of extreme hypofractionation tend to be applied to other radiotherapy techniques
      such as stereotactic radiotherapy. All these developments point to the emerging
      role of HDR brachytherapy as monotherapy for prostate cancer. 

PMID- 23543799
TI  - Photoinduced Cleavage of N-N Bonds of Aromatic Hydrazines and Hydrazides by
      Visible Light.
AB  - A photocatalytic system involving [Ru(bpyrz)3](PF6)2.2H2O, visible light, and air
      has been developed for cleavage of the N-N bonds of hydrazines and hydrazides.
      This catalytic system is generally effective for N,N-disubstituted hydrazine and
      hydrazide derivatives, including arylhydrazides, N-alkyl-N-arylhydrazines, and
      N,N-diarylhydrazines. The utility of this cleavage reaction has been demonstrated
      by synthesizing a variety of secondary aromatic amines.

PMID- 23543800
TI  - iTRAQ based quantitative proteomics approach validated the role of calcyclin
      binding protein (CacyBP) in promoting colorectal cancer metastasis.
AB  - Keeping continuity with our previous study that revealed direct correlations
      between CRC metastasis and enhanced CacyBP protein levels, here we attempt to
      improve our understanding of the mechanisms involved within this enigmatic
      process. Overexpression of CacyBP (CacyBP-OE) in primary CRC cell and its knock
      down (CacyBP-KD) in the metastatic CRC cells revealed (through phenotypic
      studies) the positive impact of the protein on metastasis. Additionally, two
      individual 4-plex iTRAQ based comparative proteomics experiments were carried out
      on the CacyBP-OE and CacyBP-KD cells, each with two biological replicates. Mining
      of proteomics data identified total 279 (63.80% up-regulated and 36.20% down
      regulated) proteins to be significantly altered in expression level for the OE
      set and in the KD set, this number was 328 (48.78% up-regulated and 51.22% down
      regulated). Functional implications of these significantly regulated proteins
      were related to metastatic phenotypes such as cell migration, invasion, adhesion
      and proliferation. Gene ontology analysis identified integrin signaling as the
      topmost network regulated within CacyBP-OE. Further detection of caveolar
      mediated endocytosis in the top hit list correlated this phenomenon with the
      dissociation of integrins from the focal adhesion complex which are known to
      provide the traction force for cell movement when transported back to the leading
      edge. This finding was further supported by the data obtained from CacyBP-KD data
      set showing down-regulation of proteins necessary for integrin endocytosis.
      Furthermore, intracellular calcium levels (known to influence integrin mediated
      cell migration) were found to be lowered in CacyBP-KD cells indicating decreased
      cell motility and vice versa for the CacyBP-OE cells. Actin nucleation by ARP
      WASP complex, known to promote cell migration, was also identified as one of the
      top regulated pathways in CacyBP-OE cells. In short, this study presents CacyBP
      as a promising candidate biomarker for CRC metastasis and also sheds light on the
      underlying molecular mechanism by which CacyBP promotes CRC metastasis. 

PMID- 23543801
TI  - Effects of nasopore packing on dacryocystorhinostomy.
AB  - PURPOSE: To investigate the effects of placement of the absorbable packing
      material Nasopore at the anastomosis site of newly formed mucosal flaps on
      postoperative re-bleeding, discomfort, and on the success rate of
      dacryocystorhinostomy (DCR). METHODS: A review of the medical records of patients
      with primary acquired nasolacrimal duct obstruction that underwent external or
      endonasal DCR by a single surgeon was performed. The degree of re-bleeding,
      discomfort, and postoperative results, including anatomical success, functional
      success and postoperative nasal findings such as granulation, synechiae, and
      membrane formation were compared in patients whose anastomosis site was packed
      with either Nasopore or Merocel, a non-absorbable packing material. RESULTS: A
      total of 77 patients (101 eyes) were included. Of the 101 eyes, 30 were packed
      with Nasopore, while 71 were packed with Merocel. The Nasopore group showed
      significantly better results than the Merocel group in the degree of re-bleeding
      and the level of patient discomfort (p = 0.000, 0.039, respectively; Pearson's
      chi-square test), whereas there were no statistically significant differences
      between the two groups in postoperative anatomical and functional success (p >
      0.05). CONCLUSIONS: Nasopore significantly reduced postoperative nasal re
      bleeding and patient discomfort during the early post-surgical period, but failed
      to show an effect on the postoperative anatomical and functional success of DCR.

PMID- 23543802
TI  - The prevalence of fungi in fingernail onychomycosis.
AB  - BACKGROUND: Fingernail onychomycosis is a fungal infection of the finger nails.
      It is mainly produced by yeasts, dermatophytes and molds and sometimes it shows a
      mixed infection. It is a cosmetic issue rather than a medical problem. AIMS: This
      study was conducted with the aim of exposing the fungal concept in nail diseases,
      to introduce nail testing which was underutilized as a diagnostic tool despite
      being involved in many dermatological conditions, as well as to introduce
      microbiological techniques in the diagnosis of nail diseases, based on the
      clinical parameters only. MATERIALS AND METHODS: A total of 45 samples were
      tested in our laboratory by using 20% KOH and culture plates of Sabouraud's
      Dextrose Agar (SDA) which were mixed with chloramphenicol and cycloheximide.
      RESULTS: A total of 37.78% samples were identified as positive by culture, among
      which 17.78% were KOH positive and 20.00% were KOH negative. 62.22% were culture
      negative. The predominant pathogen was yeast (64.71%), followed by dermatophytes
      (17.65%). A mixed infection was identified in 11.76%. Scytalidium hyalinum was
      identified in 5.88% of the cases. Fungi commonly presented in the middle age,
      between 31-40 years of age, due to trauma at the work site and in women, due to
      their wet work. CONCLUSION: This study highlighted the yeast, genus Candida as
      the main pathogen which caused fingernail onychomycosis in our region. So, it is
      imperative to diagnose it properly by using microbiological techniques and to
      treat it properly.

PMID- 23543803
TI  - 'Doctor, what would you do in my position?' Health professionals and the decision
      making process in pregnancy monitoring.
AB  - OBJECTIVE: Routine prenatal screening for Down syndrome challenges professional
      non-directiveness and patient autonomy in daily clinical practices. This paper
      aims to describe how professionals negotiate their role when a pregnant woman
      asks them to become involved in the decision-making process implied by screening.
      METHODS: Forty-one semi-structured interviews were conducted with gynaecologists
      obstetricians (n=26) and midwives (n=15) in a large Swiss city. RESULTS: Three
      professional profiles were constructed along a continuum that defines the
      relative distance or proximity towards patients' demands for professional
      involvement in the decision-making process. The first profile insists on
      enforcing patient responsibility, wherein the healthcare provider avoids any form
      of professional participation. A second profile defends the idea of a shared
      decision making between patients and professionals. The third highlights the
      intervening factors that justify professionals' involvement in decisions.
      CONCLUSIONS: These results illustrate various applications of the principle of
      autonomy and highlight the complexity of the doctor-patient relationship amidst
      medical decisions today.

PMID- 23543804
TI  - Efficacy and safety of a polyherbal sedative-hypnotic formulation NSF-3 in
      primary insomnia in comparison to zolpidem: a randomized controlled trial.
AB  - OBJECTIVES: To assess the efficacy and safety of NSF-3, a polyherbal sedative
      hypnotic (containing standardized extracts of Valeriana officinalis, Passiflora
      incarnate and Humulus lupulus), in comparison to zolpidem in primary insomnia.
      MATERIALS AND METHODS: The present study was designed as a parallel group, double
      blind, randomized, controlled trial and registered with Clinical Trials Registry
      India (CTRI/2011/12/002197). Patients diagnosed with primary insomnia with a
      perceived total sleep time of <6 hours per night and insomnia severity index >7
      were included. They were treated with either NSF-3 (one tablet) or zolpidem (one
      10 mg tablet) at bedtime for two weeks. Total sleep time, sleep latency and
      number of awakenings per night were assessed using a sleep diary. Quality of life
      and daytime sleepiness were evaluated by insomnia severity index and Epworth
      sleepiness score respectively. Vital signs, routine blood counts, liver and renal
      function tests, and treatment emergent adverse events were recorded for safety
      assessment. RESULTS: A total of 91 subjects were recruited, of which 39 in each
      group completed the study. There was significant improvement in total sleep time,
      sleep latency, number of nightly awakenings and insomnia severity index scores in
      both groups. However, no statistically significant difference was observed
      between the groups. Epworth sleepiness scores did not change significantly over
      the study period. Although 12 treatment emergent adverse events were reported
      with NSF-3 and 16 with zolpidem (commonest was drowsiness in both), most were
      mild and no serious adverse events were encountered. CONCLUSIONS: NSF-3 is a safe
      and effective short-term alternative to zolpidem for primary insomnia. It remains
      to be explored whether the benefits are sustained and whether there is dependence
      liability with this formulation upon long term use.

PMID- 23543805
TI  - Juvenile hormone esterase: biochemistry and structure.
AB  - Normal insect development requires a precisely timed, precipitous drop in
      hemolymph juvenile hormone (JH) titer. This drop occurs through a coordinated
      halt in JH biosynthesis and increase in JH metabolism. In many species, JH
      esterase (JHE) is critical for metabolism of the resonance-stabilized methyl
      ester of JH. JHE metabolizes JH with a high kcat/KM ratio that results primarily
      from an exceptionally low KM. Here we review the biochemistry and structure of
      authentic and recombinant JHEs from six insect orders, and present updated
      diagnostic criteria that help to distinguish JHEs from other carboxylesterases.
      The use of a JHE-encoding gene to improve the insecticidal efficacy of
      biopesticides is also discussed.

PMID- 23543806
TI  - Does LDL-C Estimation Using Anandaraja's Formula Give a Better Agreement with
      Direct LDL-C Estimation than the Friedewald's Formula?
AB  - Estimation of low density lipoprotein cholesterol (LDL-C) is crucial in
      management of coronary artery disease patients. Though a number of homogenous
      assays are available for estimation of LDL-C, use of calculated LDL-C by
      Friedewald's formula (FF) is common in Indian laboratories for logistic reasons.
      Recently Anandaraja and colleagues have derived a new formula for calculating LDL
      C. This formula needs to be evaluated before it is extensively applied in
      diagnosis. We measured LDL-C by homogenous method (D-LDL-C) in 515 fasting
      samples. Friedewald's and Anandaraja's formulas were used for calculation of LDL
      C (F-LDL-C and A-LDL-C, respectively). The mean LDL-C levels were 123.3 +/- 53.2,
      112.4 +/- 50.2 and 109.2 +/- 49.8 mg/dl for D-LDL-C, F-LDL-C and A-LDL-C,
      respectively. There was a statistically significant difference between the
      results (P > 0.001) obtained by calculation formulas compared to the measured LDL
      C. There was underestimation of LDL-C by 10.8 and 14 mg/dl by Friedewald's and
      Anandaraja's formulas respectively. The Pearson's correlation between F-LDL-C and
      D-LDL-C was 0.931 and that between A-LDL-C and D-LDL-C was 0.930. Bland-Altman
      graphs showed a definite agreement between mean and differences of the
      calculation formulas and direct LDL-C with 95% of values lying with in +/-2 SD
      limits. The mean percentage difference (calculated as {(Calculated LDL-C)-(D-LDL
      C)}/D-LDL-C * 100) for F-LDL-C was maximum (-11.6%) at HDL-C >= 60 mg/dl and TG
      levels of 200-300 mg/dl (-10.4%) compared to D-LDL-C. A-LDL-C results gave
      highest mean percentage difference at total cholesterol concentrations <100 mg/dl
      (-37.3%) and HDL-C < 40 mg/dl (-17.1%), respectively. The results of our study
      showed that FF is better in agreement with D-LDL-C than Anandaraja's formula for
      estimation of LDL-C by calculation though both lead to its underestimation.

PMID- 23543807
TI  - C-terminal protein characterization by mass spectrometry using combined micro
      scale liquid and solid-phase derivatization.
AB  - A sample preparation method for protein C-terminal peptide isolation has been
      developed. In this strategy, protein carboxylate glycinamidation was preceded by
      carboxyamidomethylation and optional alpha- and epsilon-amine acetylation in a
      one-pot reaction, followed by tryptic digestion of the modified protein. The
      digest was adsorbed on ZipTip(C18) pipette tips for sequential peptide alpha- and
      epsilon-amine acetylation and 1-ethyl-(3-dimethylaminopropyl) carbodiimide
      mediated carboxylate condensation with ethylenediamine. Amino group
      functionalized peptides were scavenged on N-hydroxysuccinimide-activated agarose,
      leaving the C-terminal peptide in the flow-through fraction. The use of reversed
      phase supports as a venue for peptide derivatization enabled facile optimization
      of the individual reaction steps for throughput and completeness of reaction.
      Reagents were exchanged directly on the support, eliminating sample transfer
      between the reaction steps. By this sequence of solid-phase reactions, the C
      terminal peptide could be uniquely recognized in mass spectra of unfractionated
      digests of moderate complexity. The use of the sample preparation method was
      demonstrated with low-level amounts of a model protein. The C-terminal peptides
      were selectively retrieved from the affinity support and proved highly suitable
      for structural characterization by collisionally induced dissociation. The sample
      preparation method provides for robustness and simplicity of operation using
      standard equipment readily available in most biological laboratories and is
      expected to be readily expanded to gel-separated proteins.

PMID- 23543808
TI  - Purse string suturing in a neonatal prolapsed uterus.
AB  - Prolapsed uterus in a newborn is a rare condition. We present our purse-string
      suturing as a new technique to restore it to its normal position to avoid
      complications. Prolapse is usually associated with congenital spinal defects, and
      is often resistant to simple reduction.

PMID- 23543809
TI  - DARPP-32 to quantify intracerebral hemorrhage-induced neuronal death in basal
      ganglia.
AB  - Quantification of acute brain injury in basal ganglia is essential for
      mechanistic and therapeutic studies in experimental intracerebral hemorrhage
      (ICH). Using conventional counting of degenerating cells based on morphological
      or immunohistochemical criteria, it is hard to define the boundary of the whole
      lesion area. Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) is
      a cytosolic protein highly enriched in medium-sized spiny neurons of the
      striatum. We developed new methods for quantifying lesion area by detecting the
      difference of the DARPP-32 negative area and the hematoma clot, and by measuring
      DARPP-32 protein level for semi-qualification in rat model of ICH. We found that
      DARPP-32 negative area around hematoma was present at day-1, peaked at day-3, and
      decreased at day-14 after ICH, a time course paralleled by DARPP-32 Western
      blots. The DARPP-32 negative area matched well with the necrotic area determined
      using propidium iodide. Treatment with an iron chelator, deferoxamine, attenuated
      the ICH-induced reduction in DARPP-32 protein levels. These results suggest that
      DARPP-32 is a simple and quantifiable indicator of ICH-induced neuronal death in
      basal ganglia. 

PMID- 23543810
TI  - Kindergarten children's attachment security, inhibitory control, and the
      internalization of rules of conduct.
AB  - Starting from research on relations between attachment and the development of
      self-regulation, the present study aimed to investigate research questions on
      relations among inhibitory control, internalization of rules of conduct (i.e.,
      behavior regulation, concern occasioned by others transgressions, confession,
      reparation after wrongdoing), and attachment security. Attachment security and
      internalization of rules of conduct of German kindergarten children (N = 82) were
      assessed by maternal reports. Children's inhibitory control was measured with the
      Stop-task. Regression analyses revealed that inhibitory control was positively
      related to attachment security and to internalization of rules of conduct.
      Mediational analysis using a bootstrapping approach indicated an indirect effect
      of attachment security on internalization processes via inhibitory control.
      Implications for further research on the development of inhibitory control and
      internalization of rules of conduct are discussed.

PMID- 23543811
TI  - Stromal endometriosis of the intestine: an elusive presentation with a review of
      the literature: a case report.
AB  - Although endometriosis involves the small intestine only rarely, when present,
      this condition may simulate a variety of inflammatory and sometimes neoplastic
      conditions because of its nonspecific symptoms. We are reporting here, a case of
      ileal, caecal and appendiceal endometriosis which presented in the emergency as a
      case of an acute intestinal obstruction with a long history of symptoms which
      were referable to the GI tract. The patient had the diffuse involvement of a
      segment of the ileum with mural thickening and luminal narrowing, which led to
      obstruction. The literature on small bowel endometriosis has been reviewed and
      the clinical and pathological features have been discussed.

PMID- 23543812
TI  - Trill performance components vary with age, season, and motivation in the banded
      wren.
AB  - Acoustic displays with difficult-to-execute sounds are often subject to strong
      sexual selection, because performance levels are related to the sender's
      condition or genetic quality. Performance may also vary with age, breeding stage,
      and motivation related to social context. We focused on within-male variation in
      four components of trill performance in banded wren (Thryophilus pleurostictus)
      songs: note consistency, frequency bandwidth, note rate and vocal deviation. The
      latter is a composite measure reflecting deviation from the performance limit on
      simultaneously maximizing both frequency bandwidth and note rate. We compared the
      changes in these song parameters at three time scales: over the course of years,
      across the breeding season, and at different times of the day with contrasting
      agonistic contexts. Vocal deviation decreased and note consistency increased over
      years, suggesting that experience may improve individual proficiency at singing
      trills. Consistency also increased across the season, confirming that practice is
      important for this parameter. Although there was no significant seasonal change
      in vocal deviation, one of its components, note rate, increased during the
      season. Neither vocal deviation nor consistency varied with agonistic context.
      However, note rate increased during playback experiments simulating territorial
      intrusions compared to dawn chorus singing. The magnitude of a male's increase in
      note rate was positively correlated with his aggressive behavior during the
      playback experiment. Thus consistency, bandwidth, and vocal deviation indicate
      age, whereas trill rate flexibly indicates the singer's aggressive motivation. We
      also found evidence of a within-male trade-off between vocal deviation and
      consistency.

PMID- 23543813
TI  - Characterizing the metabolic heterogeneity in human breast cancer xenografts by
      3D high resolution fluorescence imaging.
AB  - We previously reported that tumor mitochondrial redox state and its heterogeneity
      distinguished between the aggressive and the indolent breast cancer xenografts,
      suggesting novel metabolic indices as biomarkers for predicting tumor metastatic
      potential. Additionally, we reported that the identified redox biomarkers
      successfully differentiated between the normal breast tissue and the cancerous
      breast tissue from breast cancer patients. The aim of the present study was to
      further characterize intratumor heterogeneity by its distribution of
      mitochondrial redox state and glucose uptake pattern in tumor xenografts and to
      further investigate the metabolic heterogeneity of the clinical biopsy samples.
      We employed the Chance redox scanner, a multi-section cryogenic fluorescence
      imager to simultaneously image the intratumor heterogeneity in the mitochondrial
      redox state and glucose uptake at a high spatial resolution (down to 50 * 50 * 20
      MUm(3)). The mitochondrial redox state was determined by the ratio of the
      intrinsic fluorescence signals from reduced nicotinamide adenine dinucleotide
      (NADH) and oxidized flavoproteins (Fp including FAD, i.e., flavin adenine
      dinucleotide), and the glucose uptake was measured using a near-infrared
      fluorescent glucose-analogue, pyropheophorbide 2-deoxyglucosamide (Pyro-2DG).
      Significant inter- and intratumor metabolic heterogeneity were observed from our
      imaging data on various types of breast cancer xenografts. The patterns and
      degrees of heterogeneity of mitochondrial redox state appeared to relate to tumor
      size and metastatic potential. The glucose uptake was also heterogeneous and
      generally higher in tumor peripheries. The oxidized and reduced regions mostly
      corresponded with the lower and the higher pyro-2DG uptake, respectively.
      However, there were some regions where the glucose uptake did not correlate with
      the redox indices. Pronounced glucose uptake and high NADH were observed in
      certain localized areas within the tumor necrotic regions, indicative of the
      existence of viable cells which was also supported by the H&E staining.
      Significant heterogeneity of the redox state indices was also observed in
      clinical specimens of breast cancer patients. As abnormal metabolism including
      the Warburg effect (high glycolysis) plays important roles in cancer
      transformation and progression, our observations that reveal the 3D intratumor
      metabolic heterogeneity as a characteristic feature of breast tumors are of great
      importance for understanding cancer biology and developing diagnostic and
      therapeutic methods. 

PMID- 23543814
TI  - Anxiety and depression in patients with amputated limbs suffering from phantom
      pain: a comparative study with non-phantom chronic pain.
AB  - BACKGROUND: Phantom limb pain (PLP) is approximately a common condition after
      limb amputation, which potentially affects the quality of life. We aimed to
      evaluate anxiety and depression in patients with amputated limbs suffering from
      PLP and to compare these psychological dysfunctions with that of patients with
      non-phantom chronic pain. METHODS: A total number of 16 male amputees with PLP
      and 24 male age-matched patients with non-phantom chronic pain were recruited in
      this study, which was performed at Khatam-Al-Anbia Pain Clinic, Tehran, Iran. A
      validated Persian version of the hospital anxiety and depression scale (HADS) was
      used to compare two psychological dysfunctions - anxiety and depression - between
      the two groups of study. RESULTS: The mean of total anxiety score was
      significantly lower in patients with PLP (8.00 +/- 3.93 vs. 11.25 +/- 5.23; P =
      0.041) and the prevalence of anxiety caseness (HADS-A score >= 11) was also lower
      in the PLP group (25% vs. 58.3%; P = 0.112, power = 31.7%). The mean of total
      depression score was 7.69 +/- 5.51 and 9.38 +/- 6.11 in patients of PLP and
      chronic pain groups, respectively (P = 0.340, power = 15%). Consequently, the
      prevalence of depression caseness (HADS-D score >= 11) was lower in PLP patients
      (37.5% vs. 50%; P = 0.710, power = 8%). CONCLUSION: Our results indicate that
      depression and anxiety are not more common in PLP patients, whereas they are more
      prevalent in subjects with non-phantom chronic pain. These lower levels of
      anxiety and depression in PLP compared with chronic pain is a new finding that
      needs to be evaluated further, which may lead to new insights into the
      pathogenesis of phantom pain in further studies.

PMID- 23543815
TI  - The Distribution of Family Sizes Under a Time-Homogeneous Birth and Death
      Process.
AB  - The number of extant individuals within a lineage, as exemplified by counts of
      species numbers across genera in a higher taxonomic category, is known to be a
      highly skewed distribution. Because the sublineages (such as genera in a clade)
      themselves follow a random birth process, deriving the distribution of lineage
      sizes involves averaging the solutions to a birth and death process over the
      distribution of time intervals separating the origin of the lineages. In this
      article, we show that the resulting distributions can be represented by
      hypergeometric functions of the second kind. We also provide approximations of
      these distributions up to the second order, and compare these results to the
      asymptotic distributions and numerical approximations used in previous studies.
      For two limiting cases, one with a relatively high rate of lineage origin, one
      with a low rate, the cumulative probability densities and percentiles are
      compared to show that the approximations are robust over a wide range of
      parameters. It is proposed that the probability distributions of lineage size may
      have a number of relevant applications to biological problems such as the
      coalescence of genetic lineages and in predicting the number of species in living
      and extinct higher taxa, as these systems are special instances of the underlying
      process analyzed in this article.

PMID- 23543816
TI  - Cancellous screw with tension band wiring for fractures of the olecranon.
AB  - BACKGROUND: Olecranon fractures are one of the most commonly seen orthopaedic
      injuries in the emergency room. The K-wire which is used in the AO Tension Band
      Wiring (TBW) technique resists the shear better than the figure of eight wire
      alone, but, it does not add compression to the fixation strength. But, the
      cancellous screw plus the tension band wire, in combination, provides the
      strength of fixation i.e., by converting the tensile force to a compressive force
      at the fracture site, with additional resistance to the displacement due to the
      lag screw compression. OBJECTIVE: To clinically evaluate the result of the
      cancellous screw with tension band wiring for fractures of the olecranon.To
      assess the elbow joint motion and stability after the procedure. MATERIAL AND
      METHODS: Tweenty five cases of fractures of the olecranon which were treated by
      using 6.5mm AO cancellous screws with a screw length of 80-105mm with a 16 gauge
      TBW, were evaluated . All the cases were followed up and the results were
      analyzed by using a 19 point scale. RESULTS: The results which were obtained in
      our series were excellent in 15(60%) patients, good in 3(12%) patients and fair
      in 7(28%) patients and there were no poor results. CONCLUSION: The technique of
      open reduction and internal fixation with a 6.5mm AO cancellous screw and TBW, is
      a simple and effective means of treating fractures of the olecranon and it is
      based on the biomechanical principle of sound.

PMID- 23543817
TI  - Clinicopathologic assay of 15 tumor resections in a family with neurofibromatosis
      type 2.
AB  - The objective of this study is the management of multiple family members with
      multiple neurofibromatosis type 2 (NF2) related tumors of the skull base that can
      be challenging, on purely technical, decision-making, and ethical levels. These
      issues are addressed in this manuscript based on an experience treating an unique
      large family with NF2. A retrospective chart review was performed, reviewing
      clinical, radiological, surgical, and pathological data. A unique family of 17
      siblings, whose father was the proband as a sporadic mutation is reported. Over a
      4-month period, five of eight affected siblings underwent 12 procedures for
      resection of 15 different NF2-related tumors. This single family experience of
      NF2-related skull base tumors underscores the importance of preservation of
      function and quality of life as the major determinants of treatment success.

PMID- 23543818
TI  - Changes in spherical aberration after various corneal surface ablation
      techniques.
AB  - PURPOSE: The corneal change induced by refractive procedures influence both the
      postoperative refractive status and the ocular spherical aberration (SA). We
      evaluated changes in corneal SA after three types of surface ablation:
      phototherapeutic keratectomy (PTK), myopic photorefractive keratectomy (PRK), and
      myopic wavefront-guided laser epithelial keratomileusis (LASEK). METHODS: Twenty
      six eyes (25 patients) were subjected to PTK 26 eyes (14 patients) to PRK, and 34
      eyes (17 patients) to wavefront-guided LASEK. Corneal SA was measured with the
      iTrace in all patients both preoperatively and 6 months postoperatively. RESULTS:
      Six months after surgery, mean corneal SA was -0.173 +/- 0.171 um in the PTK
      group, 0.672 +/- 0.200 um in the PRK group, and 0.143 +/- 0.136 um in the
      wavefront-guided LASEK group. The mean difference between the preoperative and
      postoperative corneal SA (DeltaSA) was -0.475 um in the PTK group, 0.402 um in
      the PRK group, and -0.143 um in the wavefront-guided LASEK group. CONCLUSIONS:
      Surgically induced changes in corneal SA vary with procedure. The prediction of
      the pattern of SA change induced by various surface ablation procedures may be
      helpful for developing future surgical procedures.

PMID- 23543819
TI  - Lower Respiratory Tract Infections (LTRIs): An Insight into the Prevalence and
      the Antibiogram of the Gram Negative, Respiratory, Bacterial Agents.
AB  - BACKGROUND: Community acquired respiratory tract infections are one of the
      commonest health issues globally, which demand frequent visits to the family
      practitioners. The emergence of antibiotic resistance in the frequently isolated
      pathogens has complicated the use of the empiric therapy with traditional agents.
      AIM: This study was focused on obtaining a comprehensive insight into the
      microbial profile, its prevalence and the susceptibility patterns of the gram
      negative bacilli isolates in lower respiratory tract infections. METHODS AND
      MATERIALS: Respiratory samples which were received from the patients at a Medical
      College Hospital in North Kerala, India were processed according to the standard
      protocol over a period of one year, from April 2011 to March 2012. The
      antimicrobial susceptibility was tested by the Kirby-Bauer disc diffusion method
      as per the CLSI guidelines. The data was interpreted by using the WHO Net
      antibiotic susceptibility surveillance soft ware Results: Out of 1750 respiratory
      samples, 298(17.03%) were culture positive for gram negative bacilli. The highest
      isolation rate was observed in the 61-80 years age group with a male
      preponderance and Klebsiella pneumoniae (41.95%) was found to be the predominant
      organism. The resistance pattern varied for different organisms. Among the
      different groups of antibacterial agents which were tested, levofloxacin was
      found to be an effective oral antibacterial against the pathogens which were
      isolated. The carbapenems (imipenem and meropenem), the betalactum/betalactamase
      inhibitors (piperacillin/tazobactum) and the aminoglycosides (amikacin) were
      effective among the parenteral antibacterials. The selection of the appropriate
      antibacterial therapy should be based on the organisms which are isolated and on
      the emerging resistance to the conventional therapies. CONCLUSION: Owing to the
      increased concern which surrounds antibiotic resistance and the changing patterns
      of the bacterial pathogens, the ongoing surveillance of disease and a regular
      review of the management guidelines are critical.

PMID- 23543820
TI  - Silver nano particles prevent platelet adhesion on immobilized fibrinogen.
AB  - Vascular thrombotic disorders have emerged as a serious threat to our society.
      Platelet adhesion to fibrinogen, collagen and other platelet activators exposed
      over the atherosclerotic plaques can trigger platelet signaling events, activate
      platelets and lead to thrombotic events. Since anticoagulant and thrombolytic
      treatment strategies are usually associated with serious bleeding complications,
      preventing platelets adhesion may help to maintain platelets in an inactive
      state. In this study we tried to find out the effect of Silver nanoparticles,
      through their interaction with various platelet surface integrins on platelet
      adhesion on immobilized fibrinogen. Platelets, isolated from anti-coagulated
      human whole blood sample from healthy donors, were suspended in physiological
      buffer and each sample was divided into four tubes. In three of them 0.05, 0.5,
      and 5 MUM concentrations of Silver nanoparticles were added, fourth tube served
      as control. Platelet adhesion on immobilized fibrinogen matrices and integrin
      mediated cell signaling events were studied in all the four samples. In the
      present study we show that nanosilver prevent platelet adhesion without
      conferring any lytic effect on them and effectively prevents integrin-mediated
      platelet responses in a concentration-dependent manner.

PMID- 23543822
TI  - Mechanical Properties and Tensile Failure Analysis of Novel Bio-absorbable Mg-Zn
      Cu and Mg-Zn-Se Alloys for Endovascular Applications.
AB  - In this paper, the mechanical properties and tensile failure mechanism of two
      novel bio-absorbable as-cast Mg-Zn-Se and Mg-Zn-Cu alloys for endovascular
      medical applications are characterized. Alloys were manufactured using an ARC
      melting process and tested as-cast with compositions of Mg-Zn-Se and Mg-Zn-Cu,
      being 98/1/1 wt.% respectively. Nanoindentation testing conducted at room
      temperature was used to characterize the elastic modulus (E) and surface hardness
      (H) for both the bare alloys and the air formed oxide layer. As compared to
      currently available shape memory alloys and degradable as-cast alloys, these
      experimental alloys possess superior as-cast mechanical properties that can
      increase their biocompatibility, degradation kinetics, and the potential for
      medical device creation.

PMID- 23543821
TI  - Rational pharmacotherapy training for fourth-year medical students.
AB  - OBJECTIVES: In this study we aimed to evaluate the impact of Rational
      Pharmacotherapy (RPT) course program, reinforced by video footages, on the
      rational pharmacotherapy skills of the students. MATERIALS AND METHODS: RPT
      course program has been conducted in Dokuz Eylul University School of Medicine
      since 2008/9. The course has been organised in accordance with World Health
      Organisation (WHO) Good Prescribing Guide. The aim of the course was to improve
      the problem solving skills (methodology for selection of the (p)ersonel-drug,
      prescription writing and informing patient about his illness and drugs) and
      communication skills of students. The impact of the course has been measured by
      pre/post-test design by an objective structured clinical examination (OSCE). In
      academic year 2010/11, to further improve OSCE score of the students we added
      doctor-patient communication video footages to the RPT course programme. During
      training, the students were asked to evaluate the doctor-patient communication
      and prescription on two video footages using a checklist followed by group
      discussions. RESULTS: Total post-test OSCE score was significantly higher for
      2010/11 academic year students (n = 147) than it was for 2009/10 year students (n
      = 131). The 2010/11 academic year students performed significantly better than
      the 2009/10 academic year students on four steps of OSCE. These steps were
      "defining the patient's problem", "specifying the therapeutic objective",
      "specifying the non-pharmacological treatment" and "choosing a (drug) treatment,
      taking all relevant patient characteristics into account". CONCLUSIONS: The
      present study demonstrated that the implementation of video footages and group
      discussions to WHO/Good Prescribing Method improved the fourth-year medical
      students' performance in rational pharmacotherapy skills.

PMID- 23543823
TI  - Parotid gland tuberculosis: a case report.
AB  - Tuberculosis of the major salivary gland is a rare entity. Only 100 cases have
      been reported so far in world literature, mostly in post parotidectomy specimens.
      Here we are reporting a case of tuberculosis of parotid gland diagnosed on
      histological evaluation after surgery.

PMID- 23543824
TI  - Peptidoglycan glycosyltransferase substrate mimics as templates for the design of
      new antibacterial drugs.
AB  - Peptidoglycan (PG) is an essential net-like macromolecule that surrounds
      bacteria, gives them their shape, and protects them against their own high
      osmotic pressure. PG synthesis inhibition leads to bacterial cell lysis, making
      it an important target for many antibiotics. The final two reactions in PG
      synthesis are performed by penicillin-binding proteins (PBPs). Their
      glycosyltransferase (GT) activity uses the lipid II precursor to synthesize
      glycan chains and their transpeptidase (TP) activity catalyzes the cross-linking
      of two glycan chains via the peptide side chains. Inhibition of either of these
      two reactions leads to bacterial cell death. beta-lactam antibiotics target the
      transpeptidation reaction while antibiotic therapy based on inhibition of the GTs
      remains to be developed. Ongoing research is trying to fill this gap by studying
      the interactions of GTs with inhibitors and substrate mimics and utilizing the
      latter as templates for the design of new antibiotics. In this review we present
      an updated overview on the GTs and describe the structure-activity relationship
      of recently developed synthetic ligands.

PMID- 23543825
TI  - Cold tolerance in Osmotin transgenic tomato (Solanum lycopersicum L.) is
      associated with modulation in transcript abundance of stress responsive genes.
AB  - Our containment trials have established cold tolerance in Nicotiana tabacum
      osmotin (Nt Osm) transgenic tomato (Solanum lycopersicum L. cv. Pusa Ruby).
      Though, the stress tolerance mechanisms have been studied at physio-biochemical
      levels, molecular mechanisms underlying the tolerant response are still not well
      studied. Therefore, quantitative transcript expression of Osmotin and other
      stress responsive genes (CBF1, P5CS and APX) was studied in response to cold (4
      degrees C; 2 and 24 h) treatment in the transgenic and wild type tomato plants.
      The expression analysis revealed differential transcript regulation in the
      transgenic and wild type plants on the cold exposure. In general, the genes were
      either earlier induced or the extent of fold change in transcript expression over
      the respective untreated controls was higher in transgenic than in the wild type
      plants on cold exposure. The transcript expression data also supported the
      metabolite analysis on free Proline and ascorbate content. The results thus
      suggest that constitutive over expression of the Osmotin modulate transcript
      abundance and functional expression products of the other stress responsive genes
      thereby, imparting cold tolerance in the transgenic tomato plants. 

PMID- 23543826
TI  - A Comparison between International Obesity Task Force and Center for Disease
      Control References in Assessment of Overweight and Obesity Among Adolescents in
      Babol, Northern Iran.
AB  - OBJECTIVE: This study compares the Center for Disease Control (CDC) and
      International Obesity Task Force (IOTF) references in assessment of overweight
      and obesity among Iranian adolescents. METHODS: The data of this study was drawn
      from a cross sectional study of a representative sample of 1200 adolescents aged
      12-17 years in Babol, northern Iran. A standard procedure was used to measure
      height and weight and the body mass index was calculated. Each subject was
      classified as overweight and obese based on IOTF cut off values of BMI and CDC
      references BMI percentile sets by age and sex. The kappa coefficients were
      estimated for the degree of agreement. RESULTS: In assessment of
      obesity/overweight prevalence, the CDC and IOTF references produced a similar
      estimate by age group and sex. The maximum differences was about 1% and the kappa
      coefficients was 0.96 to 1 (P = 0.001). While for assessment of obesity, the CDC
      reference produced slightly a higher rate of obesity and the difference in
      prevalence between the two sets of references was ranged from 1.4% to 3.2% with
      kappa coefficients: 0.90 to 0.70 (P = 0.001) depending on the age group and sex
      and a greater difference was observed among younger age group. CONCLUSION: The
      findings suggest an excellent agreement between the TOTF and CDC references in
      assessment of overall overweight/obesity prevalence among adolescent boys and
      girls. While in assessment of obesity prevalence alone the degree of agreement
      between the two sets of references slightly diminished. Overall, the two
      references are comparable and the agreement varies a little with respect to age
      and sex.

PMID- 23543827
TI  - Multiple musculovascular anomalies in the superior extremities of a cadaver: a
      case report.
AB  - During the evolution from the lower animals to man, the upper limbs have acquired
      a great mobility, but at the cost of their stability. The reverse is true for the
      lower limbs. The muscular anomalies which are common in the upper limbs are
      largely explainable on a phylogenetic basis. The same is true for the vascular
      anomalies. However, such anomalies are usually seen singly and they are never
      together in the same limb or in two limbs of the same body. The upper limbs which
      are being reported here had multiple musculovascular anomalies and some of these
      were bilateral. These include the superficial brachial artery, the accessory head
      of the biceps brachii, the accessory muscular slips which arose from the common
      flexor origin and went to the tendons of the flexor digitorum profundus and the
      flexor pollicis longus separately, bifurcation of the tendon of insertion of the
      brachioradialis and bifurcated (split) insertion of the third lumbrical on the
      adjacent fingers. Though all these variations have been described in the standard
      text books of Anatomy, their occurrence, together in one limb and the bilateral
      presentations of some of these, have never been encountered. Almost all these
      variations have been explained phylogenically, thus supporting the dictum, "The
      ontogeny repeats the phylogeny." Furthermore, their clinical significance has
      also been discussed.

PMID- 23543829
TI  - An epidermal cyst in the floor of the mouth: a rare presentation.
AB  - Epidermal cysts rarely occur in the head and neck region as compared to the
      dermoid cysts and when they do occur in this region, they present in the floor of
      the mouth. We are reporting a rare case of an epidermal cyst in the floor of the
      mouth, with a brief review of the literature.

PMID- 23543828
TI  - Determining fungi rRNA copy number by PCR.
AB  - The goal of this project is to improve the quantification of indoor fungal
      pollutants via the specific application of quantitative PCR (qPCR). Improvement
      will be made in the controls used in current qPCR applications. This work focuses
      on the use of two separate controls within a standard qPCR reaction. The first
      control developed was the internal standard control gene, benA. This gene encodes
      for beta-tubulin and was selected based on its single-copy nature. The second
      control developed was the standard control plasmid, which contained a fragment of
      the ribosomal RNA (rRNA) gene and produced a specific PCR product. The results
      confirm the multicopy nature of the rRNA region in several filamentous fungi and
      show that we can quantify fungi of unknown genome size over a range of spore
      extractions by inclusion of these two standard controls. Advances in qPCR have
      led to extremely sensitive and quantitative methods for single-copy genes;
      however, it has not been well established that the rRNA can be used to quantitate
      fungal contamination. We report on the use of qPCR, combined with two controls,
      to identify and quantify indoor fungal contaminants with a greater degree of
      confidence than has been achieved previously. Advances in indoor environmental
      health have demonstrated that contamination of the built environment by the
      filamentous fungi has adverse impacts on the health of building occupants. This
      study meets the need for more accurate and reliable methods for fungal
      identification and quantitation in the indoor environment.

PMID- 23543830
TI  - Structure Activity Relationship Study of the Cleistriosides and Cleistetrosides
      for Antibacterial/Anticancer Activity.
AB  - Two known cleistriosides and six known cleistetrosides were synthesized and
      evaluated for anticancer and antibacterial activity. This study, for the first
      time, reports anticancer activity and comprehensively the antibacterial activity
      for these oligosaccharide natural products. In addition, two new unnatural
      cleistetroside analogues were synthesized and tested. Biological activities for
      the ten oligosaccharides against B. subtilis were found to range between 4 and
      >64 uM, and for NCI-H460 human lung cancer epithelial cells between 7.5 and 90.9
      uM. Similar activities were found for seven of the oligosaccharides against the
      NCI panel of 60 cell lines. The degree of acylation and location of the specific
      acetate groups had significant effects on the anticancer and antibacterial
      activity of both the cleistriosides and cleistetrosides.

PMID- 23543831
TI  - Patterning of Protein/Quantum Dot Hybrid Bionanostructures.
AB  - Here we demonstrate patterning of protein/quantum dot hybrid bionanostructures
      via electrostatic assembly of engineered negatively charged fluorescent protein
      with positively charged CdSe/ZnS QD patterns formed through e-beam lithography
      and post-patterning modification with cationic ligands.

PMID- 23543832
TI  - Effects of a novel push-through technique using the implantable collamer lens
      injector system for graft delivery during endothelial keratoplasty.
AB  - PURPOSE: To investigate effects of a new push-through insertion method for donor
      lenticules using an injector system on endothelial viability ex vivo and in a
      clinical case series of endothelial keratoplasty. METHODS: An ex vivo delivery
      model was used with porcine corneoscleral rims. We compared the endothelial
      viability in a new push-through insertion method using the Visian Implantable
      Collamer Lens (ICL) injector versus that of standard forceps-assisted insertion
      for lenticule delivery. Twenty porcine corneal lenticules were divided into four
      groups by insertion method and wound size. Vital dye staining was performed and
      devitalized areas were semi-quantitatively assessed by digital imaging. In the
      clinical case series, Descemet's stripping endothelial keratoplasty (DSEK) using
      the push-through method was performed in seven patients and endothelial outcome
      was determined six months postoperatively. RESULTS: Mean devitalized areas for
      the push-through method were significantly lower than for forceps-assisted
      insertion through 3.2 mm incision (23.99 +/- 2.17% vs. 50.48 +/- 5.07%, p =
      0.009) in the ex vivo model. Average endothelial cell counts of donor tissues of
      patients who underwent DSEK were 26.4% lower six months postoperatively.
      CONCLUSIONS: Push-through delivery of donor lenticules using the Visian ICL
      injector system appears to be less harmful to endothelial cells than conventional
      forceps-assisted delivery.

PMID- 23543833
TI  - The Profiles in Science Digital Library: Behind the Scenes.
AB  - This demonstration shows the Profiles in Science(r) digital library. Profiles in
      Science contains digitized selections from the personal manuscript collections of
      prominent biomedical researchers, medical practitioners, and those fostering
      science and health. The Profiles in Science Web site is the delivery mechanism
      for content derived from the digital library system. The system is designed
      according to our basic principles for digital library development [1]. The
      digital library includes the rules and software used for digitizing items,
      creating and editing database records and performing quality control as well as
      serving the digital content to the public. Among the types of data managed by the
      digital library are detailed item-level, collection-level and cross-collection
      metadata, digitized photographs, papers, audio clips, movies, born-digital
      electronic files, optical character recognized (OCR) text, and annotations (see
      Figure 1). The digital library also tracks the status of each item, including
      digitization quality, sensitivity of content, and copyright. Only items
      satisfying all required criteria are released to the public through the World
      Wide Web. External factors have influenced all aspects of the digital library's
      infrastructure.

PMID- 23543834
TI  - Recurrent acute pancreatitis and cholangitis in a patient with autosomal dominant
      polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder
      associated with multiple cyst formation in the different organs. Development of
      pancreatic cyst in ADPKD is often asymptomatic and is associated with no
      complication. A 38-year-old man with ADPKD was presented with six episodes of
      acute pancreatitis and two episodes of cholangitis in a period of 12 months.
      Various imaging studies revealed multiple renal, hepatic and pancreatic cysts,
      mild ectasia of pancreatic duct, dilation of biliary system and absence of
      biliary stone. He was managed with conservative treatment for each attack. ADPKD
      should be considered as a potential risk factor for recurrent acute and/or
      chronic pancreatitis and cholangitis.

PMID- 23543835
TI  - The NFTI-QOL: A Disease-Specific Quality of Life Questionnaire for
      Neurofibromatosis 2.
AB  - The objective of this study was to develop a reliable, validated disease-specific
      score measuring quality of life (QOL) in clinical practice and treatment trials
      in Neurofibromatosis 2 (NF2) individuals. In NF2 patients, qualitative interviews
      (n = 15) and a focus group session (n = 30) generated items for a pilot
      questionnaire. This was tested and refined (n = 20). The final version (NFTI-QOL)
      was validated (n = 50) with two generic QOL questionnaires (SF-36 and EuroQOL).
      The NFTI-QOL was also administered to patients with solitary vestibular
      schwannoma (SVS) (n = 30) and normal controls (n = 30). The participants were NF2
      patients, SVS patients, and normal controls. NFTI-QOL score, SF-36 score, and
      EuroQOL score were the main outcome measures. Mean NFTI-QOL score was 9.4 (range:
      0 to 20, maximum possible score = 24). The NFTI-QOL score correlated strongly
      with EuroQOL (r = 0.71, p < 0.001) and SF-36 (r = 0.81, p < 0.001). NF2
      individuals were significantly worse than the SVS patients, who in turn were
      worse than the controls on the NIFTI-QOL. The NFTI-QOL showed good internal
      reliability (Cronbach's alpha = 0.87). We developed an eight-item disease
      specific QOL score for NF2 patients, validated against SF-36 and EuroQOL. It
      correlated strongly with clinician-rated disease severity in NF2, with better
      correlation than the SF-36 in this regard.

PMID- 23543836
TI  - Anti-convulsant action and amelioration of oxidative stress by Glycyrrhiza glabra
      root extract in pentylenetetrazole- induced seizure in albino rats.
AB  - OBJECTIVES: The aim of the present study was to evaluate the anti-convulsant
      potential of aqueous and ethanol e xtract of Glycyrrhiza glabra (AEGG and EEGG)
      and its action on markers of oxidant stress in albino rats. MATERIALS AND
      METHODS: The aqueous and ethanol extract of Glycyrrhiza glabra was tested at
      three doses viz. 100, 200, and 400 mg/kg i.p. for its anti-convulsant activity
      using pentylenetetrazole (PTZ)-induced seizure in rat. The effect of EEGG (400
      mg/kg, i.p.) on oxidative stress markers like malondialdehyde (MDA), superoxide
      dismutase (SOD), and catalase (CAT) of rat brain tissue homogenate was tested.
      RESULTS: The onset of seizure was delayed (P < 0.01) by all the three doses of
      EEGG, but the duration of convulsion was reduced (P < 0.01) only in higher dose
      level (200 and 400 mg/ kg), whereas AEGG up to 400 mg/kg did not alter any of the
      parameters significantly. Biochemical analysis of rat brain tissue revealed that
      MDA was increased (P < 0.01), whereas SOD and CAT were decreased (P < 0.01) in
      PTZ-induced seizure rat, whereas pre-treatment with EEGG (400 mg/kg) decreased (P
      < 0.01) the MDA and increased (P < 0.01) both SOD and CAT, indicating attenuation
      of lipid peroxidation due to increase in antioxidant enzymes. CONCLUSION: The
      results demonstrated that EEGG poses anti-convulsant potential and ameliorates
      ROS induced neuronal damage in PTZ-induced seizure.

PMID- 23543837
TI  - The prevalence of nasal carriage of Staphylococcus aureus among healthcare
      workers at a tertiary care hospital in assam with special reference to MRSA.
AB  - BACKGROUND: The recent years have witnessed the increasing resistance of
      Staphylococcus aureus to many antimicrobial agents. The most notable example is
      the emergence of Methicillin-resistant Staphylococcus aureus (MRSA), which was
      reported just one year after the launch of methicillin. The ecological niches of
      the S. aureus strains are the anterior nares. The identification of
      Staphylococcus aureus by using a proper antibiogram and the detection of
      methicillin resistant Staphylococcus aureus greatly contribute towards the
      effective treatment of the patients. AIMS AND OBJECTIVES: To isolate
      Staphylococcus aureus from the nasal swabs of healthcare workers (HCWs) and to
      study their antimicrobial susceptibility patterns, which include methicillin
      resistance. MATERIALS AND METHODS: Nasal swabs were collected from the healthcare
      workers of various clinical departments of the hospital over a period of one
      year. The isolation of Staphylococcus aureus and their antimicrobial
      susceptibility patterns were carried out by standard bacteriological procedures.
      RESULTS: Staphylococcus aureus was isolated in 70 cases (22.22%). The prevalence
      of the S.aureus nasal carriage was higher among the male HCWs (54.28%) than among
      the female HCWs (45.71%). The carriage rate was the highest in the orthopaedics
      department, followed by those in the surgery and the gynaecology departments. All
      the Staphylococcus aureus isolates were sensitive to vancomycin and linezolid
      (100%). Penicillin and ampicillin were the most resistant, (90% and 88.6%)
      respectively. Methicillin resistance was seen in11.43% of the S.aureus isolates,
      both by the disc diffusion test and by the Oxacillin Resistance Screen Agar
      (ORSA) test. CONCLUSIONS: The compliance with the sanitary and the antibacterial
      guidelines of the health professionals is the single most important factor in
      preventing nosocomial infections. Simple preventive measures like hand washing
      before and after the patient examination, the use of sterile aprons and masks in
      the postoperative wards, awareness during the examination of the
      immunocompromised patients, and avoiding touching one's nose during work, can
      reduce the disease transmission rate considerably.

PMID- 23543839
TI  - Malignant Tumor at D-4 Mimicking Wilkie's Syndrome.
AB  - Primary carcinoma of the duodenum is rare. Here we present a case of megaduodenum
      due to duodenal adenocarcinoma mimicking Wilkie's syndrome which was managed by
      resection and anastomosis.

PMID- 23543838
TI  - Beyond human intentions and emotions.
AB  - Although significant advances have been made in our understanding of the neural
      basis of action observation and intention understanding in the last few decades
      by studies demonstrating the involvement of a specific brain network (action
      observation network; AON), these have been largely based on experimental studies
      in which people have been considered as strictly isolated entities. However, we,
      as social species, spend much more of our time performing actions interacting
      with others. Research shows that a person's position along the continuum of
      perceived social isolation/bonding to others is associated with a variety of
      physical and mental health effects. Thus, there is a crucial need to better
      understand the neural basis of intention understanding performed in interpersonal
      and emotional contexts. To address this issue, we performed a meta-analysis using
      of functional magnetic resonance imaging (fMRI) studies over the past decade that
      examined brain and cortical network processing associated with understanding the
      intention of others actions vs. those associated with passionate love for others.
      Both overlapping and distinct cortical and subcortical regions were identified
      for intention and love, respectively. These findings provide scientists and
      clinicians with a set of brain regions that can be targeted for future
      neuroscientific studies on intention understanding, and help develop
      neurocognitive models of pair-bonding.

PMID- 23543840
TI  - Feelings of Gratitude Toward God Among Older Whites, Older African Americans, and
      Older Mexican Americans.
AB  - The first goal of this study is to see if social relationships in the church
      influence feelings of gratitude toward God. The second goal is to assess the
      impact of race and ethnicity on this relationship. The data support the following
      hypotheses: (1) older people who go to church more often tend to receive more
      spiritual support from fellow church members; (2) older adults who receive more
      spiritual support at church will derive a deeper understanding of themselves and
      others; (3) older people who develop greater insight into themselves and others
      will derive a greater sense of religious meaning in life; and (4) older adults
      who develop a deeper sense of religious meaning in life will feel more grateful
      to God. The results also indicate that the study model explains how feelings of
      gratitude toward God arise among older blacks and whites, but not older Mexican
      Americans.

PMID- 23543841
TI  - Molecular design of the phenol type extractants.
AB  - A method of optimisation of new extractants structure using the desirable
      function has been developed. Earlier the desirable function has been proposed by
      Harrington (Ind Qual Control 21: 494-498, 1965) for the optimisation of processes
      with several response functions. The developed method of optimisation of new
      extractants structure has been used for construction of phenolic type extractants
      (PTE) (a class of N-(2-hydroxy-5-nonylbenzil)-dialkylamines). It has been offered
      to use the charge on the nitrogen atom, the heat of dissociation of phenolic
      group, the logarithm of distribution factor of extractant between water and
      octanol (computed data) and maximum permissible concentration of extractants in
      aqueous phase (MPC) of the o-replaced phenols (the literary data) as the
      controllable parameters, defining efficiency of extractants for molecular design
      of PTE. During optimisation of extractants structure the quantity of alkyl
      substitutes at nitrogen atom, the carbon atoms number in these substitutes and
      the electronegative substitutes in o-position to phenolic group have been varied.
      As the result of the molecular design, the optimal structure of PTE found is N
      (2,3-dihydroxy-5-nonylbenzil)-didecylamine, which perfectly meets the
      requirements to industrial extractants. 

PMID- 23543842
TI  - A rare case of the lenz syndrome.
AB  - We are reporting here, a case of the Lenz syndrome in a neonate who was brought
      to the Paediatric OPD, Kasturba Medical College Hospital, Attavar, Mangalore
      India, with the complaints of poor suckling since birth and abnormal facial
      features. Altogether, the characteristic congenital abnormal findings in Lenz
      syndrome, which comprise of microophthalmia, ear anomalies, microcephaly,
      skeletal and digital deformities, and urogenital malformations were observed,
      with an exception of a dental anomaly. Dental abnormalities were not pertinent,
      as the patient was a neonate.

PMID- 23543843
TI  - Askin's Tumour in an Adult, with a Varied Clinical Presentation.
AB  - We are reporting a case of Askin's tumour in a 28 year old male, on the right
      side of the chest wall, with no symptoms and signs of a pulmonary involvement or
      a distant metastasis. A wide excision of the tumour mass was done.
      Immunohistochemistry strongly expressed MIC-2. The prognosis of Askin's tumour is
      poor. An early diagnosis and treatment are important to improve the chances of a
      survival.

PMID- 23543844
TI  - Impact of Dual Disorders, Trauma, and Social Support on Quality of Life Among
      Women in Treatment for Substance Dependence.
AB  - OBJECTIVE: Women with dual disorders report lower levels of social support than
      women with substance dependence alone, and lower levels of social support have
      been associated with lower quality of life among individuals with substance use
      disorders. However, little is known about the impact of trauma symptoms and
      violence exposure on quality of life for women with dual disorders. The purpose
      of this study was to examine the impact of dual disorders, trauma, and social
      support related to recovery on various domains of quality of life among women in
      substance abuse treatment. METHODS: This study utilized multiple standardized
      measures and hierarchical ordinary least squares regression to examine quality of
      life, trauma, and social support in women with dual disorders. Four domains of
      quality of life were measured (Physical, Psychological, Social, and Environmental
      Domains). Participants (N=369) were recruited from three inner city women only
      addiction treatment programs. IRB approval was obtained prior to sample
      recruitment. RESULTS: Presence of a dual disorder was significantly associated
      with lower quality of life in the Physical and Psychological domains. However,
      this difference was no longer significant when trauma symptoms were added to the
      model. Trauma symptoms and Support for Recovery significantly predicted quality
      of life across all four domains and Friends Support for Abstinence across three
      domains. CONCLUSIONS: Findings suggest that the presence of a dual disorder in
      women may indicate a history of trauma. They also support the importance of both
      friend's support for abstinence and recovery support as predictors of quality of
      life in women with dual disorders. Interventions that focus on social support and
      quality of life in treatment with women with substance use disorders may
      potentially enhance treatment outcomes.

PMID- 23543845
TI  - Sugar is an endogenous cue for juvenile-to-adult phase transition in plants.
AB  - The transition from the juvenile to adult phase in plants is controlled by
      diverse exogenous and endogenous cues such as age, day length, light, nutrients,
      and temperature. Previous studies have shown that the gradual decline in
      microRNA156 (miR156) with age promotes the expression of adult traits. However,
      how age temporally regulates the abundance of miR156 is poorly understood. We
      show here that the expression of miR156 responds to sugar. Sugar represses miR156
      expression at both the transcriptional level and post-transcriptional level
      through the degradation of miR156 primary transcripts. Defoliation and
      photosynthetic mutant assays further demonstrate that sugar from the pre-existing
      leaves acts as a mobile signal to repress miR156, and subsequently triggers the
      juvenile-to-adult phase transition in young leaf primordia. We propose that the
      gradual increase in sugar after seed germination serves as an endogenous cue for
      developmental timing in plants. DOI:http://dx.doi.org/10.7554/eLife.00269.001.

PMID- 23543846
TI  - Refractive changes after removal of anterior IOLs in temporary piggyback IOL
      implantation for congenital cataracts.
AB  - PURPOSE: To assess the refractive change and prediction error after temporary
      intraocular lens (IOL) removal in temporary polypseudophakic eyes using IOL power
      calculation formulas and Gills' formula. METHODS: Four consecutive patients (7
      eyes) who underwent temporary IOL explantation were enrolled. Postoperative
      refractions calculated using IOL power calculation formulas (SRK-II, SRK-T,
      Hoffer-Q, Holladay, and the modified Gills' formula for residual myopia and
      residual hyperopia) were compared to the manifest spherical equivalents checked
      at 1 month postoperatively. RESULTS: The mean ages of temporary piggyback IOL
      implantation and IOL removal were 6.71 +/- 3.68 months (range, 3 to 12 months)
      and 51.14 +/- 18.38 months (range, 29 to 74 months), respectively. The average
      refractive error was -13.11 +/- 3.10 diopters (D) just before IOL removal, and
      improved to -1.99 +/- 1.04 D after surgery. SRK-T showed the best prediction
      error of 1.17 +/- 1.00 D. The modified Gills' formula for myopia yielded a
      relatively good result of 1.47 +/- 1.27 D, with only the variable being axial
      length. CONCLUSIONS: Formulas to predict refractive change after temporary IOL
      removal in pediatric polypseudophakia were not as accurate as those used for
      single IOL implantation in adult eyes. Nonetheless, this study will be helpful in
      predicting postoperative refraction after temporary IOL removal.

PMID- 23543847
TI  - Identifying the Non-recurrent Laryngeal Nerve: Preventing a Major Risk of
      Morbidity During Thyroidectomy.
AB  - Non-recurrent laryngeal nerve (NRLN) is a rare anomaly which is reported in 0.3%
      0.8% of people on the right side and in 0.004% (extremely rare) on the left side.
      Damage to this nerve during the surgical procedure may lead to severe iatrogenic
      morbidity and should therefore be prevented from being damaged. The best way to
      avoid this damage to the nerve is to identify the nerve with a systematic
      diligent dissection based on usual anatomical landmarks and awareness about the
      possibility of their existence. Hereby, we are going to present a 26-year-old
      woman, a case of NRLN on the right side which was identified during
      thyroidectomy. The nervous anomaly was accompanied with vascular abnormality
      which was confirmed by computerized tomography (CT) angiography, post
      operatively.

PMID- 23543848
TI  - The Dynamics of Global Chromatin Remodeling are Pivotal for Tracking the Normal
      Pluripotency of Human Embryonic Stem Cells.
AB  - Pluripotent Human Embryonic Stem Cells (hESCs) have the unconstrained capacity
      for long-term stable undifferentiated growth in culture and unrestricted
      developmental capacity. Packaging of the eukaryotic genome into chromatin confers
      higher order structural control over maintaining stem cell plasticity and
      directing differentiation. We recently reported the establishment of a defined
      culture system for sustaining the epiblast pluripotence of hESCs, serving as a
      platform for de novo derivation of clinically-suitable hESCs and effectively
      directing such hESCs uniformly towards functional lineages. To unveil the
      epigenetic mechanism in maintaining the epiblast pluripotence of hESCs, in this
      study, the global chromatin dynamics in the pluripotent hESCs maintained under
      the defined culture were examined. This study shows that the genomic plasticity
      of pluripotent hESCs is enabled by an acetylated globally active chromatin
      maintained by Oct-4. The pluripotency of hESCs that display normal stable
      expansion is associated with high levels of expression and nuclear localization
      of active chromatin remodeling factors that include acetylated histone H3 and H4,
      Brg-1, hSNF2H, HAT p300, and HDAC1; weak expression or cytoplasmic localization
      of repressive chromatin remodeling factors that are implicated in transcriptional
      silencing; and residual H3 K9 methylation. A dynamic progression from acetylated
      to transient hyperacetylated to hypoacetylated chromatin states correlates with
      loss-of-Oct4-associated hESC differentiation. RNA interference directed against
      Oct-4 and HDAC inhibitor analysis support this pivotal link between chromatin
      dynamics and hESC differentiation. These findings reveal an epigenetic mechanism
      for placing global chromatin dynamics as central to tracking the normal
      pluripotency and lineage progression of hESCs.

PMID- 23543849
TI  - Cardioprotective effect of Saraca indica against cyclophosphamide induced
      cardiotoxicity in rats: a biochemical, electrocardiographic and histopathological
      study.
AB  - OBJECTIVES: Cardioprotective activity of alcoholic extract of Saraca indica (SI)
      bark was investigated against cyclophosphamide induced cardiotoxicity. MATERIALS
      AND METHODS: Cardiotoxicity was induced in Wistar rats by administering
      cyclophosphamide (200 mg/kg, i.p.) single injection on first day of experimental
      period. Saraca indica (200 and 400 mg/kg, p.o.) was administered immediately
      after administration of cyclophosphamide on first day and daily for 10 days. The
      general observations and mortality were measured. RESULTS: Cyclophosphamide
      administration significantly (p < 0.05) increased lipid peroxidation (LPO) and
      decreased the levels of antioxidant markers such as reduced glutathione (GSH),
      superoxide dismutase (SOD) and catalase (CAT). Cyclophosphamide elevated the
      levels of biomarker enzymes like creatine kinase (CK), creatine kinase isoenzyme
      MB (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine
      transaminase (ALT) and alkaline phosphatase (ALP). Further, the cyclophosphamide
      treated rats showed changes in electrocardiogram (ECG) along with increased
      levels of cholesterol and triglycerides. Treatment with Saraca indica
      significantly (p < 0.05) reversed the status of cardiac biomarkers, ECG,
      oxidative enzymes and lipid profile in cyclophosphamide induced cardiotoxicity.
      Potential cardioprotective effect of Saraca indica was supported by
      histopathological examination that reduced severity of cellular damage of the
      myocardium. CONCLUSION: The biochemical, ECG and histopathology reports support
      the cardioprotective effect of Saraca indica which could be attributed to
      antioxidant activity.

PMID- 23543850
TI  - The Evaluation of Carotid Atherosclerosis in Patients with the HIV-1 Infection:
      The Role of the Antiretroviral Therapy.
AB  - BACKGROUND AND OBJECTIVE: The recognition and the assessment of the carotid
      intimal thickness helps in predicting the risk of the cardiovascular events in
      Human Immunodeficiency Virus (HIV) infected patients who are on Antiretroviral
      Therapy (ART). The objective of this study was to assess and compare the carotid
      intimal thickness in HIV positive individuals who were on antiretroviral therapy
      with HIV positive individuals who were not on anti-retroviral therapy. SUBJECTS
      AND METHODS: All the HIV positive individuals who were 20 years old and above,
      who had been diagnosed by the National AIDS Control Organization (NACO)
      guidelines were included in the study. The HIV positive individuals who were
      diagnosed with diabetes mellitus and hypertension were excluded from the study.
      The study subjects were divided into 2 groups i.e. HIV patients who were on anti
      retroviral therapy and HIV patients who were not on anti-retroviral therapy. The
      patients had to be on anti-retroviral therapy for a minimum of 6 months for them
      to be included in the first group. The data was collected by using a semi
      structured, pre-tested proforma, which included the demographic details, the
      duration of the HIV infection, details of the antiretroviral treatment, a history
      of smoking/ alcohol consumption and details on the assessments of the metabolic
      syndrome. RESULTS: A total of 42 patients were included in the study. Among them,
      28 were males (66.7%) and 14 were females (33.3%). Twenty six patients were on
      ART and the remaining patients were treatment naive. There were significant
      differences with regards to their age and the duration of the HIV infection,
      which was longer in the patients who were on ART (p= 0.049, p=0.003
      respectively). The Body Mass Index (BMI), the waist: hip ratio, the mid-arm
      circumference, the waist circumference, the skin fold thickness and the carotid
      intimal-media thickness were higher in the HIV patients who were on ART as
      compared to those in the treatment naive patients, though the difference was
      statistically insignificant. CONCLUSION: The carotid intimal thickness was higher
      in the HIV patients who were on ART as compared to those in the treatment naive
      HIV infected patients.

PMID- 23543851
TI  - A Cellular Automata Model of Infection Control on Medical Implants.
AB  - S. epidermidis infections on medically implanted devices are a common problem in
      modern medicine due to the abundance of the bacteria. Once inside the body, S.
      epidermidis gather in communities called biofilms and can become extremely hard
      to eradicate, causing the patient serious complications. We simulate the complex
      S. epidermidis-Neutrophils interactions in order to determine the optimum
      conditions for the immune system to be able to contain the infection and avoid
      implant rejection. Our cellular automata model can also be used as a tool for
      determining the optimal amount of antibiotics for combating biofilm formation on
      medical implants.

PMID- 23543852
TI  - Exploring the movement dynamics of deception.
AB  - BOTH THE SCIENCE AND THE EVERYDAY PRACTICE OF DETECTING A LIE REST ON THE SAME
      ASSUMPTION: hidden cognitive states that the liar would like to remain hidden
      nevertheless influence observable behavior. This assumption has good evidence.
      The insights of professional interrogators, anecdotal evidence, and body language
      textbooks have all built up a sizeable catalog of non-verbal cues that have been
      claimed to distinguish deceptive and truthful behavior. Typically, these cues are
      discrete, individual behaviors-a hand touching a mouth, the rise of a brow-that
      distinguish lies from truths solely in terms of their frequency or duration.
      Research to date has failed to establish any of these non-verbal cues as a
      reliable marker of deception. Here we argue that perhaps this is because simple
      tallies of behavior can miss out on the rich but subtle organization of behavior
      as it unfolds over time. Research in cognitive science from a dynamical systems
      perspective has shown that behavior is structured across multiple timescales,
      with more or less regularity and structure. Using tools that are sensitive to
      these dynamics, we analyzed body motion data from an experiment that put
      participants in a realistic situation of choosing, or not, to lie to an
      experimenter. Our analyses indicate that when being deceptive, continuous
      fluctuations of movement in the upper face, and somewhat in the arms, are
      characterized by dynamical properties of less stability, but greater complexity.
      For the upper face, these distinctions are present despite no apparent
      differences in the overall amount of movement between deception and truth. We
      suggest that these unique dynamical signatures of motion are indicative of both
      the cognitive demands inherent to deception and the need to respond adaptively in
      a social context.

PMID- 23543853
TI  - FDG-PET/CT of sarcoidosis and sarcoid reactions following antineoplastic
      treatment.
AB  - Sarcoidosis or sarcoid reactions, which appear as FDG-avid lesions in oncologic
      patients, need to be differentiated from disseminated malignancies. We aimed to
      promote awareness of development of sarcoidosis or sarcoid reactions after
      antineoplastic therapy to avoid diagnostic errors with FDG-PET/CT findings and
      assess the utility of FDG-PET/CT for follow-up. We retrospectively reviewed
      radiological reports of FDG-PET/CT scans performed between January 2009 and
      December 2011. Among oncologic patients with more than 2 FDG-PET/CT scans, those
      with nearly symmetrical increases in FDG uptake in the hilar or mediastinal lymph
      nodes were identified, and those with known sarcoidosis, concurrent diagnoses of
      sarcoidosis with malignancy, or histopathologically proven malignancies were
      excluded. Then, only those cases were selected for which sarcoidosis or sarcoid
      reactions were diagnosed. Four of 376 oncologic cases met the criteria. At 9
      months to 6 years after antineoplastic therapy, abnormal FDG uptakes were
      observed in the hilar, mediastinal, abdominal, pelvic, and inguinal nodes, and/or
      spleen and lung parenchyma with SUVmax up to 17.7. On the basis of these
      findings, 1 patient received anticancer chemotherapy because of tumor recurrence
      suspicion. A gradual decrease in FDG uptake was observed on subsequent PET/CT
      scans. Sarcoidosis or sarcoid reactions should be considered in differential
      diagnosis of oncologic patients who have developed FDG-avid lesions any time
      after antineoplastic therapy. FDG-PET/CT can be used for follow-up in
      nondiagnostic situations to detect decreases in FDG uptake due to presence of
      sarcoidal granulomas. 

PMID- 23543854
TI  - Anomalous origin of the hepatic artery from the hepatomesenteric trunk.
AB  - During the routine dissection of the abdominal cavity of a 75 years old,
      embalmed, male cadaver in the Department of Anatomy, an anomalous origin of the
      common hepatic artery from the hepatomesenteric trunk was observed. The
      Hepatomesenteric trunk originated from the ventral surface of the aorta at the L1
      level. After coursing anteriorly, the trunk divided into the common hepatic
      artery and the superior mesenteric artery. The common hepatic artery is normally
      a branch of the coeliac trunk, but in the present case, the coeliac trunk gave
      two branches i.e. the left gastric and the splenic arteries. The length and the
      external diameter of the variant arteries were measured by using a Vernier
      calliper. The type V of Adachi's classification resembled closely with the
      variation which was observed. A knowledge on such a variation is important to
      avoid upheavals during surgical procedures. It is also helpful for the
      radiologists in interventional processes such as embolization of the hepatic
      artery and chemotherapy.

PMID- 23543855
TI  - Conducting Functional Communication Training via Telehealth to Reduce the Problem
      Behavior of Young Children with Autism.
AB  - Functional communication training (FCT) was conducted by parents of 17 young
      children with autism spectrum disorders who displayed problem behavior. All
      procedures were conducted at regional clinics located an average of 15 miles from
      the families' homes. Parents received coaching via telehealth from behavior
      consultants who were located an average of 222 miles from the regional clinics.
      Parents first conducted functional analyses with telehealth consultation (Wacker,
      Lee, et al., in press) and then conducted FCT that was matched to the identified
      function of problem behavior. Parent assistants located at the regional clinics
      received brief training in the procedures and supported the families during the
      clinic visits. FCT, conducted within a nonconcurrent multiple baseline design,
      reduced problem behavior by an average of 93.5%. Results suggested that FCT can
      be conducted by parents via telehealth when experienced applied behavior analysts
      provide consultation.

PMID- 23543856
TI  - Relationship between the morphology of diabetic macular edema and renal
      dysfunction in diabetes.
AB  - PURPOSE: To determine the correlation between renal dysfunction and the
      morphologic changes of macular edema in diabetes. METHODS: The current study
      included 93 patients with diabetic macular edema based on optical coherence
      tomography (OCT) who completed systemic condition testing one month before or
      after the OCT. Based on the OCT findings, patients were divided into the
      following five groups: group A (diffuse), group B (cystoid), group C (serous),
      group D (vitreomacular tractional), and group E (a mixed presence of cystoid and
      serous types). In each group, we performed a retrospective analysis of serum
      albumin, urine albumin, and serum creatinine. We also analyzed the patients in
      whom serum albumin was <3.0 mg/dL and serum creatinine was >1.6 mg/dL. Urine
      albumin was measured in all five groups. In each group, a comparative analysis
      was performed using Fisher's exact test. RESULTS: The number of patients who were
      assigned to groups A to E was 15, 46, 6, 3, and 23, respectively. According to a
      comparison of the patients in whom the serum albumin and serum creatinine were
      abnormal, there was no significant difference among the five groups. The
      proportion of patients in whom the urine albumin was abnormal was significantly
      greater in group C (67%) than in groups A (7%), B (20%), or E (22%). CONCLUSIONS:
      Serous-type macular edema occurred more frequently than other types of macular
      edema in patients with albuminuria.

PMID- 23543857
TI  - Copy Number Variation within Human beta-Defensin Gene Cluster Influences
      Progression to AIDS in the Multicenter AIDS Cohort Study.
AB  - STUDY BACKGROUND: DEFB4/103A encoding beta-defensin 2 and 3, respectively,
      inhibit CXCR4-tropic (X4) viruses in vitro. We determined whether DEFB4/103A Copy
      Number Variation (CNV) influences time-to-X4 and time-to-AIDS outcomes. METHODS:
      We utilized samples from a previously published Multicenter AIDS Cohort Study
      (MACS), which provides longitudinal account of viral tropism in relation to the
      full spectrum of rates of disease progression. Using traditional models for time
      to-event analysis, we investigated association between DEFB4/103A CNV and the two
      outcomes, and interaction between DEFB4/103A CNV and disease progression groups,
      Fast and Slow. RESULTS: Time-to-X4 and time-to-AIDS were weakly correlated. There
      was a stronger relationship between these two outcomes for the fast progressors.
      DEFB4/103A CNV was associated with time-to-AIDS, but not time-to-X4. The
      association between higher DEFB4/103A CNV and time-to-AIDS was more pronounced
      for the slow progressors. CONCLUSION: DEFB4/103A CNV was associated with time-to
      AIDS in a disease progression group-specific manner in the MACS cohort. Our
      findings may contribute to enhancing current understanding of how genetic
      predisposition influences AIDS progression.

PMID- 23543858
TI  - Evaluation of sesamol and buspirone in stress induced anxiety in mice.
AB  - OBJECTIVES: The present study was designed to elucidate the effects of sesamol,
      buspirone and their combination in immobilization stress induced behavioral and
      biochemical alterations in mice. MATERIALS AND METHODS: Male Laca mice (divided
      into 10 groups with 6 animals each) were pre-treated with sesamol (5 and 10
      mg/kg; p.o.), buspirone (5 and 10 mg/kg; p.o.) and combination of sesamol (5 and
      10 mg/kg; p.o.) with buspirone (5 mg/kg; p.o.) for consecutive five days. On the
      6(th) day, animals were immobilized for 6 h and various behavioral tests such as
      body weight, locomotor activity, mirror chamber test and elevated plus maze were
      carried out. Biochemical estimations such as lipid peroxidation and nitrite
      concentration, glutathione and catalase levels were done. Data was analyzed using
      One way ANOVA followed by Tukey's test (P < 0.05) was considered statistical
      significant. RESULTS: Immobilization stress significantly (P < 0.05) impaired
      body weight, locomotor activity, induced anxiety like behavioral and oxidative
      damage as compared to naomicronve animal. Pretreatment with sesamol (5 and 10
      mg/kg; p.o.) and buspirone (5 and 10 mg/ kg; p.o.) significantly (P < 0.05)
      improved body weight, locomotor activity, and anxiety like behavior in mirror
      chamber as well as plus maze performance tasks and anti-oxidant like effect as
      evidenced by reduced lipid peroxidation, nitrite concentration and restoration of
      reduced glutathione and catalase activity as compared to control animals.
      Further, co- administration of sesamol (5 and 10 mg/kg) with buspirone (5 mg/kg)
      significantly (P < .05) potentiated the anti anxiety effects as compared to their
      effects alone. CONCLUSIONS: The present study suggests that combination of
      sesamol and buspirone potentiated the antianxiety effects against anxiety induced
      by immobilization stress and oxidative damage in mice.

PMID- 23543859
TI  - Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by
      diethylnitrosamine in alcohol-fed rats.
AB  - Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which
      is associated with hepatocarcinogenesis. We investigated whether treatment with
      chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated
      hepatic carcinogenesis in rats. Rats were fed either an ethanol liquid diet or a
      non-ethanol liquid diet, with or without CMZ for one and ten months. A single
      intraperitoneal injection of diethylnitrosamine (DEN, 20 mg/kg) was given to
      initiate hepatic carcinogenesis. CYP2E1 expression, inflammatory proteins, cell
      proliferation, protein-bound 4-HNE, etheno-DNA adducts, 8-hydroxy-2'
      deoxyguanosine (8-OHdG), retinoid concentrations, and hepatic carcinogenesis were
      examined. Ethanol feeding for 1 month with DEN resulted in significantly
      increased hepatic CYP2E1 levels and increased nuclear accumulation of NF-kappaB
      protein and TNF-alpha expression, which were associated with increased cyclin D1
      expression and p-GST positive altered hepatic foci. All of these changes induced
      by ethanol feeding were significantly inhibited by the one month CMZ treatment.
      At 10-months of treatment, hepatocellular adenomas were detected in ethanol-fed
      rats only, but neither in control rats nor in animals receiving ethanol and CMZ.
      The 8-OHdG formation was found to be significantly increased in ethanol fed
      animals and normalized with CMZ treatment. In addition, alcohol-reduced hepatic
      retinol and retinoic acid concentrations were restored by CMZ treatment to normal
      levels in the rats at 10 months of treatment. These data demonstrate that the
      inhibition of ethanol-induced CYP2E1 as a key pathogenic factor can counteract
      the tumor-promoting action of ethanol by decreasing TNF-alpha expression, NF
      kappaB activation, and oxidative DNA damage as well as restoring normal hepatic
      levels of retinoic acid in DEN-treated rats.

PMID- 23543860
TI  - Incentive Motivation, Cognitive Control, and the Adolescent Brain: Is It Time for
      a Paradigm Shift?
AB  - It can be argued that adolescents' decision making is biased more by motivational
      factors than by cognitively driven calculations of outcome probabilities. Brain
      based models, derived from structural and functional neuroimaging perspectives to
      account for this bias, have focused on purported differences in rates of
      development of motivational and regulatory-control systems. This article proposes
      a neurochemically based framework for understanding adolescents' behavioral
      biases_and suggests that there should be an increased focus on the dopaminergic
      substrates of incentive motivation, which increases into adolescence and
      decreases thereafter. The article also discusses the manner in which this
      increase interacts with executive control systems in affecting self-regulation.

PMID- 23543861
TI  - Imagining the future: Community perceptions of a family-based economic
      empowerment intervention for AIDS-orphaned adolescents in Uganda.
AB  - AIDS-orphaned children and adolescents in sub-Saharan Africa have inadequate
      access to basic services, including health and education. Using a qualitative
      approach, the study explores the meaning of education in rural Uganda, obstacles
      faced by AIDS-orphaned adolescents and their caregivers to access secondary
      education, and the potential of an economic empowerment intervention SEED in
      addressing the challenges of accessing educational opportunities for AIDS
      orphaned adolescents. The findings come from 29 semi-structured interviews
      conducted with eleven adolescents study participants, four caregivers and
      fourteen community leaders involved in the pilot SEED intervention. Study
      participants and community members indicated that the savings accounts offer a
      unique opportunity for orphaned adolescents to stay in school and imagine the
      future with optimism.

PMID- 23543862
TI  - Low temperature geomicrobiology follows host rock composition along a geochemical
      gradient in lau basin.
AB  - The East Lau Spreading Center (ELSC) and Valu Fa Ridge (VFR) comprise a ridge
      segment in the southwest Pacific Ocean where rapid transitions in the underlying
      mantle chemistry manifest themselves as gradients in seafloor rock geochemistry.
      We studied the geology and microbial diversity of three silicate rock samples and
      three inactive sulfide chimney samples collected, from north to south, at the
      vent fields Kilo Moana, ABE, Tui Malila, and Mariner. This is the first study of
      microbial populations on basaltic andesite, which was sampled at Mariner vent
      field. Silicate rock geochemistry exhibits clear latitudinal trends that are
      mirrored by changes in bacterial community composition. alpha-proteobacteria,
      epsilon-proteobacteria, and Bacteroidetes are most common on a silicate collected
      from Kilo Moana and their proportions decrease linearly on silicates collected
      further south. Conversely, a silicate from Mariner vent field hosts high
      proportions of a unique lineage of Chloroflexi unrelated (<90% sequence
      similarity) to previously recovered environmental clones or isolates, which
      decrease at ABE and are absent at Kilo Moana. The exteriors of inactive sulfide
      structures are dominated by lineages of sulfur oxidizing alpha-proteobacteria,
      gamma-proteobacteria, and epsilon-proteobacteria, while the interior of one
      chimney is dominated by putative sulfur-reducing delta-proteobacteria. A
      comparison of bacterial communities on inactive sulfides from this and previous
      studies reveals the presence of a clade of uncultured Bacteroidetes exclusive to
      sulfidic environments, and a high degree of heterogeneity in bacterial community
      composition from one sulfide structure to another. In light of the heterogeneous
      nature of bacterial communities observed here and in previous studies of both
      active and inactive hydrothermal sulfide structures, the presence of numerous
      niches may be detected on these structures in the future by finer scale sampling
      and analysis.

PMID- 23543863
TI  - Comparative Evaluation of Gingival Depigmentation using Tetrafluoroethane
      Cryosurgery and Gingival Abrasion Technique: Two Years Follow Up.
AB  - OBJECTIVE: A comparative evaluation of the gingival depigmentation by using
      Tetrafluoroethane cryosurgery and the gingival abrasion technique - 2 years of
      follow up. MATERIAL AND METHODS: Ten systemically healthy patients who were aged
      18 to 36 years were selected for the study. Tetrafluoroethane was used for the
      cryosurgical depigmentation and the gingival abrasion technique used a coarse
      flame shaped bur. The presence or absence of pigmentation was tabulated, based on
      the GPI (Gingival Pigmentation Index). For the statistical analysis, Freidman's
      test was used. RESULTS: The keratinization was completed within a week after the
      application of the cryogen and about 10 days after the gingival abrasion
      technique was done. The statistical analysis which was done after 90th, 180th
      days and 2 years. The p-value which was obtained (p<.001) showed the superiority
      of cryosurgery over the gingival abrasion. During the follow up period, no side
      effects were seen for both the techniques and the improved aesthetics was
      maintained upto 2 years. CONCLUSION: The use of cryogen Tetrafluoroethane is
      easy, practical and inexpensive as compared to gingival abrasion, due to its high
      rate of recurrence. Hence, it is more acceptable to the patients and the
      operator. Further studies are needed to assess the long term effectiveness of the
      cryosurgical method of depigmentation.

PMID- 23543864
TI  - Mass and Ion Transport in Ketones and Ketone Electrolytes: Comparison with
      Acetate Systems.
AB  - Self-diffusion coefficient measurements were performed for pure n-alkyl ketone
      liquids using the pulsed field gradient NMR spin-echo technique. Ionic
      conductivities and dielectric constants of 0.0055 mol.L-1 tetrabutylammonium
      trifluoromethanesulfonate in 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 2
      nonanone, and 2-decanone were also measured. The temperature-dependent
      conductivities and diffusion coefficients over the range 5-80  degrees C can be
      described using the compensated Arrhenius formalism. Compensated Arrhenius
      equation plots were used to calculate the average activation energy for both sets
      of data. The average activation energy from conductivity data is approximately
      equal to that from diffusion data. The data for the pure ketones and ketone-based
      electrolytes are compared with analogous data for pure n-alkyl acetates and n
      alkyl acetate-based electrolytes.

PMID- 23543865
TI  - Factors influencing the seasonal patterns of infectious diseases.
AB  - The recognition of seasonal patterns in infectious disease occurrence dates back
      at least as far as the hippocratic era, but the mechanisms underlying these
      fluctuations remain poorly understood. Many classes of mechanistic hypotheses
      have been proposed to explain seasonality of various directly transmitted
      diseases, including at least the following; human activity, seasonal variability
      in human immune system function, seasonal variations in vitamin D levels,
      seasonality of melatonin, and pathogen infectivity. In this short paper will
      briefly discuss the role of these factors in the seasonal patterns of infectious
      diseases.

PMID- 23543866
TI  - Instruction Matters: Spelling of Vowels by Children in England and the US.
AB  - Letter names are stressed in informal and formal literacy instruction with young
      children in the US, whereas letters sounds are stressed in England. We examined
      the impact of these differences on English children of about 5 and 6 years of age
      (in reception year and Year 1, respectively) and US 6 year olds (in
      kindergarten). Children in both countries spelled short vowels, as in bag, more
      accurately than long vowels, as in gate. The superiority for short vowels was
      larger for children from England, consistent with the instructional emphasis on
      letter sounds. Errors such as gat for words with long vowels such as gate were
      more common among US children, reflecting these children's use of vowels' names
      as a guide to spelling. The English children's performance on a letter knowledge
      task was influenced by the fact that they are often taught letter sounds with
      reference to lowercase letters and letter names with reference to uppercase
      letters, and their spellings showed some effects of this practice. Although
      emphasis on letter sounds as opposed to letter names influences children's
      patterns of performance and types of errors, it does not make the difficult
      English writing system markedly easier to master.

PMID- 23543867
TI  - Survival benefits of terlipressin and non-responder state in hepatorenal
      syndrome: a meta-analysis.
AB  - OBJECTIVES: Terlipressin improves renal function in hepatorenal syndrome (HRS) is
      a known fact. However the reason for lack of its long-term survival benefits
      despite improvement in renal function remains unclear. The aim of this study was
      to analyze the survival benefits of terlipressin in HRS and to address the issue
      of non-responder state to terlipressin. MATERIALS AND METHODS: Electronic
      databases and relevant articles were searched for all types of studies related to
      HRS and use of terlipressin in HRS. Reduction in all-cause mortality rate was the
      primary outcome measure. Reduction in mortality rate due to HRS and other causes
      of death were also analyzed. RESULTS: With total 377 patients analyzed from eight
      eligible studies; terlipressin reduced all-cause mortality rate by 15% (Risk
      Difference: -0.15%, 95% CI:-0.26 to -0.03). Reduction in the mortality rate due
      to HRS at three months was 9% (Risk Difference:-0.09%, 95% CI:-0.18 to 0.00).
      CONCLUSION: Terlipressin has long term survival benefits perhaps at least up to
      three months but only with HRS as a cause of death not for other causes of death.
      Benefits and role of antioxidants like N- Acetylcysteine (NAC) in non-responder
      patients' needs to be studied further. Long-term use of low dose terlipressin (<4
      mg/d) plus albumin and addition of antioxidant NAC to this regimen may help in
      improving both HRS reversal rate and survival rate in non-responders to
      terlipressin.

PMID- 23543868
TI  - Drug Resistant Breast Cancer Cell Line Displays Cancer Stem Cell Phenotype and
      Responds Sensitively to Epigenetic Drug SAHA.
AB  - Cancer stem cell (CSC) population in solid human breast tumor was identified by
      CD44(+)/CD24(-) phenotype, characterized by high tumorigenicity, invasiveness and
      drug resistance. In this study, we characterized drug resistant breast cancer
      cell line-MCF-7/Adr and a number of breast cancer cell lines using flow
      cytometry, immunofluorescence, mammosphere formation assay and migration assay,
      examining their CSC immunophenotypes, presence of CSC proteins, tumorigenicity in
      vitro and migratory rates, respectively. Our results show that MCF-7/Adr cells
      uniformly display CSC characteristics yet retain low migratory rate. They are
      also able to self-renew and differentiate under floating culture conditions.
      Furthermore, MCF-7/Adr is selectively sensitive to epigenetic drug,
      suberoylanilide hydroxamic acid (SAHA), losing drug resistance and changes
      morphology yet retaining CSC immunophenotypes. In conclusion, we show that
      resistant breast cancer cell line MCF-7/Adr demonstrates uniform CSC like
      characteristics and are sensitive to epigenetic drug treatment. 

PMID- 23543869
TI  - Correlation of MTDH/AEG-1 and HOTAIR Expression with Metastasis and Response to
      Treatment in Sarcoma Patients.
AB  - BACKGROUND: Chemoresistance and metastasis are the main reasons for the failure
      of current treatments with sarcoma patients. Novel biomarkers are required to
      predict metastasis and response to treatment. The oncogene MTDH/AEG1 and the long
      noncoding RNA (lincRNA) HOTAIR are two novel factors involved in drug resistance
      and metastasis in various types of solid tumors. However, the correlation between
      MTDH/AEG-1 and HOTAIR expression with metastasis and drug resistance in sarcoma
      is unknown. METHODS: Expression of MTDH protein or HOTAIR was detected by Western
      blotting or qRT-PCR, respectively, in primary and metastatic sarcoma patient
      tissue samples. RESULTS: High individual or co-expression of MTDH/AEG1 and HOTAIR
      was observed in three of four primary and six of eight metastatic sarcoma patient
      tumor samples. High level expression of both of MTDH/AEG1 and HOTAIR in the
      primary tumor correlated with a likelihood to metastasize. MTDH expression was
      lower in samples pre-treated with irradiation and/or chemotherapy as compared to
      those that had not been treated. HOTAIR expression seemed to correlate with the
      percent necrosis seen in different sarcoma samples. CONCLUSIONS: High levels of
      both MTDH/AEG-1 and HOTAIR in primary sarcoma are correlated with a high
      probability of metastasis. By contrast, reduced expression of both MTDH/AEG-1 and
      HOTAIR is correlated with a good response to treatment in terms of necrosis,
      suggesting that levels of MTDH and HOTAIR are potential biomarkers for treatment
      efficacy. Whether we can predict disease progression in sarcoma remains to be
      seen. Additional study is needed to better define the best clinical application
      of MTDH/AEG-1 and HOTAIR expression with metastasis and outcome.

PMID- 23543870
TI  - An Advanced, Interactive, High-Performance Liquid Chromatography Simulator and
      Instructor Resources.
AB  - High-Performance Liquid Chromatography (HPLC) simulation software has long been
      recognized as an effective educational tool, yet we found that existing HPLC
      simulators are either too expensive, out-dated, or lack many important features
      we deemed necessary to make them widely useful for educational purposes. Here we
      describe a free, open-source HPLC simulator we developed that we believe meets
      this need. The web-based simulator is uniquely sophisticated, yet accessible to a
      diverse user group with varied expertise in HPLC. It features intuitive controls
      and indicators for a wide range of experimental conditions, and it displays a
      graphical chromatogram to provide immediate feedback when conditions are changed.
      The simulator can be found at hplcsimulator.org. At that website, we also provide
      a number of example problem sets that can be used by educators to more easily
      incorporate the simulator into their curriculum. Comments from students who used
      the simulator in an undergraduate Analytical Chemistry class were very positive.

PMID- 23543871
TI  - S-Nitrosation Mediates Multiple Pathways That Lead to Tumor Progression in
      Estrogen Receptor-Negative Breast Cancer.
AB  - Chronic inflammation within the tumor microenvironment is a major driver of tumor
      progression and poor prognosis. Inducible nitric oxide synthase (NOS2) is present
      in numerous solid tumors. Estrogen receptor-negative (ER-) patients with high
      expression of tumor NOS2 have a poorer outcome than patients with low expression
      of NOS2. Furthermore, expression of NOS2 is associated with the basal-like breast
      cancer phenotype. Using an in vitro model, we have found that nitrosation of
      critical thiols and nitration of tyrosines lead to the activation of membrane
      receptors such as epithelial growth factor receptor, Src, Ras, and CD63. These
      nitric oxide-mediated events in itiate oncogenic signaling pathways such as
      PI3K/Akt, Ras/ERK, beta-catenin, nuclear factor-kappaB, and AP-1. These data
      suggest that NOS2 can serve as a major "nonmutatational driver" of ER- breast
      cancer.

PMID- 23543872
TI  - Closed-loop response properties of a visual interneuron involved in fly optomotor
      control.
AB  - Due to methodological limitations neural function is mostly studied under open
      loop conditions. Normally, however, nervous systems operate in closed-loop where
      sensory input is processed to generate behavioral outputs, which again change the
      sensory input. Here, we investigate the closed-loop responses of an identified
      visual interneuron, the blowfly H1-cell, that is part of a neural circuit
      involved in optomotor flight and gaze control. Those behaviors may be triggered
      by attitude changes during flight in turbulent air. The fly analyses the
      resulting retinal image shifts and performs compensatory body and head rotations
      to regain its default attitude. We developed a fly robot interface to study H1
      cell responses in a 1 degree-of-freedom image stabilization task. Image shifts,
      induced by externally forced rotations, modulate the cell's spike rate that
      controls counter rotations of a mobile robot to minimize relative motion between
      the robot and its visual surroundings. A feedback controller closed the loop
      between neural activity and the rotation of the robot. Under these conditions we
      found the following H1-cell response properties: (i) the peak spike rate
      decreases when the mean image velocity is increased, (ii) the relationship
      between spike rate and image velocity depends on the standard deviation of the
      image velocities suggesting adaptive scaling of the cell's signaling range, and
      (iii) the cell's gain decreases linearly with increasing image accelerations. Our
      results reveal a remarkable qualitative similarity between the response dynamics
      of the H1-cell under closed-loop conditions with those obtained in previous open
      loop experiments. Finally, we show that the adaptive scaling of the H1-cell's
      responses, while maximizing information on image velocity, decreases the cell's
      sensitivity to image accelerations. Understanding such trade-offs in biological
      vision systems may advance the design of smart vision sensors for autonomous
      robots.

PMID- 23543873
TI  - Microglial control of neuronal activity.
AB  - Fine-tuning of neuronal activity was thought to be a neuron-autonomous mechanism
      until the discovery that astrocytes are active players of synaptic transmission.
      The involvement of astrocytes has changed our understanding of the roles of non
      neuronal cells and shed new light on the regulation of neuronal activity.
      Microglial cells are the macrophages of the brain and they have been mostly
      investigated as immune cells. However, recent data discussed in this review
      support the notion that, similarly to astrocytes, microglia are involved in the
      regulation of neuronal activity. For instance, in most, if not all, brain
      pathologies a strong temporal correlation has long been known to exist between
      the pathological activation of microglia and dysfunction of neuronal activity.
      Recent studies have convincingly shown that alteration of microglial function is
      responsible for pathological neuronal activity. This causal relationship has also
      been demonstrated in mice bearing loss-of-function mutations in genes
      specifically expressed by microglia. In addition to these long-term regulations
      of neuronal activity, recent data show that microglia can also rapidly regulate
      neuronal activity, thereby acting as partners of neurotransmission.

PMID- 23543875
TI  - Production of HlyA and ClyA haemolysins among quinolone-resistant Escherichia
      coli isolated from clinical samples.
AB  - Most Escherichia coli resistant to quinolones are not haemolytic. The objective
      of this study was to determine the phylogroup, clonal relationship, mechanism of
      quinolone resistance and virulence factors in 70 haemolytic E. coli resistant to
      nalidixic acid. Sixty-six isolates contained the hlyA gene, belonged to
      phylogroup B2, and 61 of them presented low-level resistance to fluoroquinolones.
      Four isolates presented high-level resistance to fluoroquinolones, contained the
      clyA gene and were included in phylogroup D. One single isolate (phylogroup D,
      with low level resistance to fluoroquinolones) contained both cytotoxins. 

PMID- 23543874
TI  - Epidemiologic evidence on serum adiponectin level and lipid profile.
AB  - The concentration of adiponectin, a hormone which is secreted from adipose
      tissue, is inversely correlated with body fat mass. This hormone has anti
      inflammatory and anti atherogenic properties. Its concentration reduces in
      metabolic syndrome and cardiovascular diseases. This study reviews the evidence
      on the relationship between serum adiponectin concentration and lipid profile. In
      this study former clinical trials, cross sectional and prospective studies have
      been reviewed. The PubMed search engine has been used to find related research
      for the topic by considering dyslipidemia, total cholesterol (TC), high and low
      density protein (HDL and LDL), triglyceride (TG), lipid profile (LP) and
      adiponectin as the key words. Finally, 25 articles were recruited to review in
      the present article. Serum adiponectin level was positively correlated with
      plasma HDL cholestrol concentrations. There was a significant inverse
      relationship between plasma triglyceride and serum adiponectin. An inverse
      correlation between very low density lipoprotein (VLDL) and LDL levels and
      adiponectin was reported from the studies. So, Adiponectin has an important role
      in the metabolism of lipid profile including HDLc.

PMID- 23543876
TI  - Biochemical and histopathological effects on liver due to acute oral toxicity of
      aqueous leaf extract of Ecliptaalba on female Swiss albino mice.
AB  - BACKGROUND: Limited data is available about the toxicity of herbal remedies used
      for self-medication. Since a popular medicinal plant Ecliptaalba contains various
      bioactive molecules, the present study aimed to observe the biochemical and
      histological changes in liver associated with acute oral toxicity (LD50) of
      aqueous extract of E. alba (L.) Hassk. in female Swiss albino mice. MATERIALS AND
      METHODS: For the acute oral toxicity study, the animals were divided into six
      groups of 6 mice each. Group- I was normal control and the treatment groups were
      administered aqueous leaf extract of E. alba orally at different doses of 500 mg
      (group - I),1750 mg (group-III), 2000 mg (group- IV), 2500 mg (group- V) and 3000
      mg/ kg/b.wt.(group- VI) for seven consecutive days. The mice were sacrificed on
      the eighth day and blood was collected for the analysis of ALP (alkaline
      phosphatase), SGPT (serum glutamic pyruvic transferase), total protein and
      albumin. The liver was dissected, weighed, and processed for histopathological
      analysis. RESULTS: The LD50 was found to be 2316.626 mg/kg /body weight in female
      mice. Serum SGPT, total protein and albumin increased in treated group- IV (P <
      0.05), V (P < 0.01), and VI (P < 0.01) as compared to the control (group- I). ALP
      level significantly decreased in the treated group- IV (P < 0.05), V (P < 0.01)
      and VI (P < 0.01). Histopathological changes were observed at dose of 2000 mg
      (group- IV), 2500 mg (group- V) and 3000 mg (group- VI). CONCLUSION: It was
      concluded that oral administration of aqueous leaf extract of E. alba had
      detrimental effects on biochemical parameters and induced histopathological
      alterations in liver of female Swiss albino mice at doses higher than 2000
      mg/kg/day indicating that its indiscriminate use should be avoided.

PMID- 23543877
TI  - Studies Toward the Synthesis of (-)-Zampanolide: Preparation of the Macrocyclic
      Core.
AB  - Studies towards the synthesis of the macrocyclic core of (-)-zampanolide are
      reported. The synthetic approach features a one-pot reduction/vinylogous aldol
      reaction for construction of the C15-C20 fragment, an intramolecular silyl
      modified Sakurai (ISMS) reaction for construction of the 2,6-cis-disubstituted
      exo-methylene pyran subunit, and use of an sp2-sp3 Stille reaction for
      macrocyclization.

PMID- 23543878
TI  - Orthodontic Camouflage Treatment in an Adult Patient with a Class II, Division 1
      Malocclusion - A Case Report.
AB  - Since so many decades, various treatment modalities have been presented for the
      treatment for the class II, div 1 malocclusions. In recent times, we have seen
      enormously increasing numbers of young adults who desire the shortest, cost
      effective and a non surgical correction of Class II malocclusions and they accept
      dental camouflage as a treatment option to mask the skeletal discrepancy. This
      case report presents one such case of a 22 year old non-growing female who had a
      skeletal Class II, division 1 malocclusion with an orthognathic maxilla, a
      retrognathic mandible, a negative VTO and an overjet of 12mm, who did not want a
      surgical treatment. We considered the camouflage treatment by extracting the
      upper first premolars. Following the treatment, a satisfactory result was
      achieved with an ideal, static and a functional occlusion, facial profile, smile
      and lip competence and stability of the treatment results.

PMID- 23543879
TI  - Changes in alkaline band formation and calcification of corticated charophyte
      Chara globularis.
AB  - Calcification by charophytes improves the quality of water, although most studies
      on calcification have only examined ecorticate species. We investigated the
      formation and relationship of alkalines and acids with regard to calcification on
      internodal cells in Chara corallina, an ecorticate species, and Chara globularis,
      a corticate species. We observed that alkaline and acidic areas with distinct
      banding patterns form on the internodal cells of C. corallina. The entire
      periphery of internodal cells was alkalized, and no distinct acidic area
      developed in C. globularis. By electron microscopy of these internodal cells, the
      calcified areas occurred primarily in alkaline areas with a banding pattern in C.
      coralline. However, phenomenon also occurred homogeneously inside of the entire
      cortex and cell wall in C. globularis. We also investigated the formation and
      relatiohship of alkalines and acids with regard to calcification on internodal
      cells of various ages from a single thallus of C. globularis. For internodal
      cells of C. globularis, a uniform calcified area lay between the cell wall and
      cortex on all cells, irrespective of age. In contrast, young cells bore an
      alkaline area that was uniform and widespread throughout their entire periphery,
      but the alkaline area in older cells was split into smaller segments in a banding
      pattern. Acidic areas were absent in young cells. These results indicate that the
      mechanisms by which alkaline and acid areas form differ in the presence and
      absence of cortex and between species. 

PMID- 23543880
TI  - Does Unemployment Lead to Greater Alcohol Consumption?
AB  - Using panel data from Waves 1 and 2 of the NESARC, we estimate gender-specific
      effects of changes in employment status on overall alcohol consumption, binge
      drinking episodes, and a diagnosis of alcohol abuse and/or dependence. We employ
      various fixed-effects models to address potential bias from unobserved and time
      invariant individual heterogeneity. All results show a positive and significant
      effect of unemployment on drinking behaviors and the findings are robust to
      numerous sensitivity tests. Perhaps macroeconomic policy decisions intended to
      stimulate the economy during economic downturns should also consider the avoided
      personal costs and externalities associated with alcohol misuse.

PMID- 23543882
TI  - Child center closures: Does nonprofit status provide a comparative advantage?
AB  - Reliable access to dependable, high quality childcare services is a vital concern
      for large numbers of American families. The childcare industry consists of
      private nonprofit, private for-profit, and governmental providers that differ
      along many dimensions, including quality, clientele served, and organizational
      stability. Nonprofit providers are theorized to provide higher quality services
      given comparative tax advantages, higher levels of consumer trust, and management
      by mission driven entrepreneurs. This study examines the influence of ownership
      structure, defined as nonprofit, for-profit sole proprietors, for-profit
      companies, and governmental centers, on organizational instability, defined as
      childcare center closures. Using a cross sectional data set of 15724 childcare
      licenses in California for 2007, we model the predicted closures of childcare
      centers as a function of ownership structure as well as center age and capacity.
      Findings indicate that for small centers (capacity of 30 or less) nonprofits are
      more likely to close, but for larger centers (capacity 30+) nonprofits are less
      likely to close. This suggests that the comparative advantages available for
      nonprofit organizations may be better utilized by larger centers than by small
      centers. We consider the implications of our findings for parents, practitioners,
      and social policy.

PMID- 23543881
TI  - Dissociable circuits for visual shape learning in the young and aging human
      brain.
AB  - Recognizing objects in cluttered scenes is vital for successful interactions in
      our complex environments. Learning is known to play a key role in facilitating
      performance in a wide range of perceptual skills not only in young but also older
      adults. However, the neural mechanisms that support our ability to improve visual
      form recognition with training in older age remain largely unknown. Here, we
      combine behavioral and fMRI measurements to identify the brain circuits involved
      in the learning of global visual forms in the aging human brain. Our findings
      demonstrate the learning enhances perceptual sensitivity in the discrimination of
      visual forms similarly in both young and older adults. However, using fMRI we
      show that the neural circuits involved in visual form learning differ with age.
      Our results show that in young adults visual shape learning engages a network of
      occipitotemporal, parietal, and frontal regions that is known to be involved in
      perceptual decisions. In contrast, in older adults visual shape learning engages
      primarily parietal regions, suggesting a stronger role of attentionally-guided
      learning in older age. Interestingly, learning-dependent changes are maintained
      in higher occipitotemporal and posterior parietal regions, but not in frontal
      circuits, when observers perform a control task rather than engaging in a visual
      form discrimination task. Thus, learning may modulate read-out signals in
      posterior regions related to global form representations independent of the task,
      whereas task-dependent frontal activations may reflect changes in sensitivity
      with training in the context of perceptual decision making.

PMID- 23543883
TI  - In vitro selection of transgenic sugarcane callus utilizing a plant gene encoding
      a mutant form of acetolactate synthase.
AB  - Selection genes are routinely used in plant genetic transformation protocols to
      ensure the survival of transformed cells by limiting the regeneration of non
      transgenic cells. In order to find alternatives to the use of antibiotics as
      selection agents, we followed a targeted approach utilizing a plant gene,
      encoding a mutant form of the enzyme acetolactate synthase, to convey resistance
      to herbicides. The sensitivity of sugarcane callus (Saccharum spp. hybrids, cv.
      NCo310) to a number of herbicides from the sulfonylurea and imidazolinone classes
      was tested. Callus growth was most affected by sulfonylurea herbicides,
      particularly 3.6 MUg/l chlorsulfuron. Herbicide-resistant transgenic sugarcane
      plants containing mutant forms of a tobacco acetolactate synthase (als) gene were
      obtained following biolistic transformation. Post-bombardment, putative
      transgenic callus was selectively proliferated on MS medium containing 3 mg/l 2,4
      dichlorophenoxyacetic acid (2,4-D), 20 g/l sucrose, 0.5 g/l casein, and 3.6 MUg/l
      chlorsulfuron. Plant regeneration and rooting was done on MS medium lacking 2,4-D
      under similar selection conditions. Thirty vigorously growing putative transgenic
      plants were successfully ex vitro-acclimatized and established under glasshouse
      conditions. Glasshouse spraying of putative transgenic plants with 100 mg/l
      chlorsulfuron dramatically decreased the amount of non-transgenic plants that had
      escaped the in vitro selection regime. PCR analysis showed that six surviving
      plants were als-positive and that five of these expressed the mutant als gene.
      This report is the first to describe a selection system for sugarcane
      transformation that uses a selectable marker gene of plant origin targeted by a
      sulfonylurea herbicide.

PMID- 23543884
TI  - Translation and cultural adaptation of the oxford hip score for Iranian
      population.
AB  - INTRODUCTION: In recent years, outcome assessment related to orthopedic surgeries
      has increasingly focused on patient-reported questionnaires. The Oxford Hip Score
      (OHS), self-administered questionnaire, is a reliable, valid, and responsive
      instrument for assessing hip in patients undergoing Arthroplasty. METHODS: The
      study involved 105 adult Persian-speaking patients admitted for primary Total Hip
      Arthroplasty in two hospitals in Isfahan in Iran from September 2009 until April
      2011. All of them filled out their scales (Persian OHS, WOMAC, and SF12) in
      preoperative examination. RESULTS: Mean scores of OHS in first administrations
      was 42.7 +/- 12.7. The Persian OHS overall score demonstrated high
      reproducibility (ICC,0.93, P < 0.001) and internal consistency (CA, 0.94).
      PersianOHS had high correlations with WOMAC total score (r = 0.86), function
      score (r = 0.86), and pain score (r = 0.79), the relationship between the Persian
      OHS and the WOMAC stiffness subscale was somewhat lower (r = 0.69). The
      correlation coefficient between the Persian OHS and the PCS of the SF-12 in our
      study was moderate (r = 0.58). Persian OHS had low correlation with MCS of the SF
      12 (r = 0.40). DISCUSSION: Persian OHS had high correlations with WOMAC total
      score, function score, and pain score. It had moderate correlation with PCS of
      the SF-12 and low correlation with MCS of the SF-12. CONCLUSIONS: Our study
      demonstrated the trans-cultural adaptation and validation of the Persian OHS is a
      reliable and practicable instrument for assessment of function and pain in
      Iranian patients with hip osteoarthritis.

PMID- 23543885
TI  - Multiple splenic artery aneurysms secondary to extra hepatic portal vein
      obstruction.

PMID- 23543886
TI  - Why personalized medicine will fail if we stay the course.
AB  - Genomic science and associated technologies are providing scientists and
      clinicians with novel insights that are transforming the delivery of healthcare
      and the overall well-being of society. However, these insights inform us that
      historical population sampling approaches for investigating rare and common
      genetic variations are not representative of the complex ancestral backgrounds of
      today's patients. In order for personalized medicine to be meaningful and
      applicable to the global populations, we will need to know how common and rare
      genetic variants found in different parts of the world influence health and drug
      response. This article demonstrates the importance of increasing ethnic and
      racial diversity among participants in genomic research, highlights areas of
      opportunity for improving our understanding of genomic diversity among
      populations, and provides examples of successful models that help to resolve
      these concerns.

PMID- 23543887
TI  - Water flows, energy demand, and market analysis of the informal water sector in
      Kisumu, Kenya.
AB  - In rapidly growing urban areas of developing countries, infrastructure has not
      been able to cope with population growth. Informal water businesses fulfill unmet
      water supply needs, yet little is understood about this sector. This paper
      presents data gathered from quantitative interviews with informal water business
      operators (n=260) in Kisumu, Kenya, collected during the dry season. Sales
      volume, location, resource use, and cost were analyzed by using material flow
      accounting and spatial analysis tools. Estimates show that over 76% of the city's
      water is consumed by less than 10% of the population who have water piped into
      their dwellings. The remainder of the population relies on a combination of water
      sources, including water purchased directly from kiosks (1.5 million m3 per day)
      and delivered by hand-drawn water-carts (0.75 million m3 per day). Energy audits
      were performed to compare energy use among various water sources in the city.
      Water delivery by truck is the highest per cubic meter energy demand (35 MJ/m3),
      while the city's tap water has the highest energy use overall (21,000 MJ/day). We
      group kiosks by neighborhood and compare sales volume and cost with neighborhood
      level population data. Contrary to popular belief, we do not find evidence of
      price gouging; the lowest prices are charged in the highest-demand low-income
      area. We also see that the informal sector is sensitive to demand, as the number
      of private boreholes that serve as community water collection points are much
      larger where demand is greatest.

PMID- 23543889
TI  - Microbiologically active Mannich bases derived from 1,2,4-triazoles. The effect
      of C-5 substituent on antibacterial activity.
AB  - Our research proved that chemical character of the C-5 substituent significantly
      determines the antibacterial activity of the Mannich bases derived from 4,5
      disubstituted 1,2,4-triazole-3-thiones. This activity was considerably increased
      by an introduction of a chlorine atom to the phenyl ring. The obtained compounds
      were particularly active against opportunistic bacteria (Bacillus subtilis and
      Bacilluscereus). The antibacterial activity of some Mannich bases was similar or
      higher than the activity of commonly used antibiotics such as ampicillin and
      cefuroxime.

PMID- 23543888
TI  - Mapping the spatio-temporal structure of motor cortical LFP and spiking
      activities during reach-to-grasp movements.
AB  - Grasping an object involves shaping the hand and fingers in relation to the
      object's physical properties. Following object contact, it also requires a fine
      adjustment of grasp forces for secure manipulation. Earlier studies suggest that
      the control of hand shaping and grasp force involve partially segregated motor
      cortical networks. However, it is still unclear how information originating from
      these networks is processed and integrated. We addressed this issue by analyzing
      massively parallel signals from population measures (local field potentials,
      LFPs) and single neuron spiking activities recorded simultaneously during a
      delayed reach-to-grasp task, by using a 100-electrode array chronically implanted
      in monkey motor cortex. Motor cortical LFPs exhibit a large multi-component
      movement-related potential (MRP) around movement onset. Here, we show that the
      peak amplitude of each MRP component and its latency with respect to movement
      onset vary along the cortical surface covered by the array. Using a comparative
      mapping approach, we suggest that the spatio-temporal structure of the MRP
      reflects the complex physical properties of the reach-to-grasp movement. In
      addition, we explored how the spatio-temporal structure of the MRP relates to two
      other measures of neuronal activity: the temporal profile of single neuron
      spiking activity at each electrode site and the somatosensory receptive field
      properties of single neuron activities. We observe that the spatial
      representations of LFP and spiking activities overlap extensively and relate to
      the spatial distribution of proximal and distal representations of the upper
      limb. Altogether, these data show that, in motor cortex, a precise spatio
      temporal pattern of activation is involved for the control of reach-to-grasp
      movements and provide some new insight about the functional organization of motor
      cortex during reaching and object manipulation.

PMID- 23543890
TI  - A knowledge representation approach using fuzzy cognitive maps for better
      navigation support in an adaptive learning system.
AB  - In this paper a knowledge representation approach of an adaptive and/or
      personalized tutoring system is presented. The domain knowledge should be
      represented in a more realistic way in order to allow the adaptive and/or
      personalized tutoring system to deliver the learning material to each individual
      learner dynamically taking into account her/his learning needs and her/his
      different learning pace. To succeed this, the domain knowledge representation has
      to depict the possible increase or decrease of the learner's knowledge.
      Considering that the domain concepts that constitute the learning material are
      not independent from each other, the knowledge representation approach has to
      allow the system to recognize either the domain concepts that are already partly
      or completely known for a learner, or the domain concepts that s/he has
      forgotten, taking into account the learner's knowledge level of the related
      concepts. In other words, the system should be informed about the knowledge
      dependencies that exist among the domain concepts of the learning material, as
      well as the strength on impact of each domain concept on others. Fuzzy Cognitive
      Maps (FCMs) seem to be an ideal way for representing graphically this kind of
      information. The suggested knowledge representation approach has been implemented
      in an e-learning adaptive system for teaching computer programming. The
      particular system was used by the students of a postgraduate program in the field
      of Informatics in the University of Piraeus and was compared with a corresponding
      system, in which the domain knowledge was represented using the most common used
      technique of network of concepts. The results of the evaluation were very
      encouraging. 

PMID- 23543891
TI  - First Report on Self-Rated Health in a Nationally-Representative Sample of
      Iranian Adolescents: The CASPIAN-iii study.
AB  - OBJECTIVE: To evaluate predictive factors of adolescents' appraisal of their
      health. METHODS: The nationwide study, entitled "Childhood and Adolescence
      Surveillance and Prevention of Adult Non-communicable Diseases (CASPIAN) study",
      was conducted in 2010 among Iranian school students, aged 10-18. In addition to
      demographic factors and physical examination, variables as family structure,
      nutrition habits, physical activity, smoking, hygienic habits, violence, school
      attachment, family smoking, and family history of chronic diseases were assessed.
      The dependent variable is the self-rated health (SRH) and it was measured by 12
      items, which had already been combined through latent class analysis. We had
      taken a dichotomous variable, i.e. the higher values indicate better SRH. The
      dependent variable was regressed on all predictors by generalized additive
      models. RESULTS: 75% of adolescents had a good SRH. The linear and smooth effects
      of independent variables on SRH were observed. Among all the variables, physical
      activity had a positive linear effect on SRH (beta = 0.08, P value = 0.003).
      Smoking, violence, and family history of disease associated to SRH non-linearly
      (P value < 0.05). Family smoking (beta = -0.01) and hygienic habits (beta = 0.27)
      related to SRH both linearly and non-linearly. CONCLUSIONS: Physical health and
      high risk behavior, either of linear or non-linear effect, are factors, which
      seem to shape the adolescents' perception of health.

PMID- 23543892
TI  - Ochronotic spondyloarthropathy.

PMID- 23543893
TI  - Radiative and Non-Radiative Lifetime Engineering of Quantum Dots in Multiple
      Solvents by Surface Atom Stoichiometry and Ligands.
AB  - CdTe quantum dots have unique characteristics that are promising for applications
      in photoluminescence, photovoltaics or optoelectronics. However, wide variations
      of the reported quantum yields exist and the influence of ligand-surface
      interactions that are expected to control the excited state relaxation processes
      remains unknown. It is important to thoroughly understand the fundamental
      principles underlying these relaxation processes to tailor the QDs properties to
      their application. Here, we systematically investigate the roles of the surface
      atoms, ligand functional groups and solvent on the radiative and non-radiative
      relaxation rates. Combining a systematic synthetic approach with X-ray
      photoelectron, quantitative FT-IR and time-resolved visible spectroscopies, we
      find that CdTe QDs can be engineered with average radiative lifetimes ranging
      from nanoseconds up to microseconds. The non-radiative lifetimes are
      anticorrelated to the radiative lifetimes, although they show much less
      variation. The density, nature and orientation of the ligand functional groups
      and the dielectric constant of the solvent play major roles in determining charge
      carrier trapping and excitonic relaxation pathways. These results are used to
      propose a coupled dependence between hole-trapping on Te atoms and strong ligand
      coupling, primarily via Cd atoms, that can be used to engineer both the radiative
      and non-radiative lifetimes.

PMID- 23543894
TI  - Genome-Scale Mapping of MicroRNA Signatures in Human Embryonic Stem Cell
      Neurogenesis.
AB  - To date, lacking of a clinically-suitable source of engraftable human
      stem/progenitor cells with adequate neurogenic potential has been the major
      setback in developing effective cell-based therapies against a wide range of
      neurological disorders. Derivation of human embryonic stem cells (hESCs) provides
      a powerful tool to investigate the molecular controls in human embryonic
      neurogenesis as well as an unlimited source to generate the diversity of human
      neuronal cell types in the developing CNS for repair. However, realizing the
      developmental and therapeutic potential of hESCs has been hindered by
      conventional multi-lineage differentiation of pluripotent cells, which is
      uncontrollable, inefficient, highly variable, difficult to reproduce and scale
      up. We recently identified retinoic acid (RA) as sufficient to induce the
      specification of neuroectoderm direct from the pluripotent state of hESCs under
      defined platform and trigger progression to human neuronal progenitors (hESC-I
      hNuPs) and neurons (hESC-I hNus) in the developing CNS with high efficiency,
      which enables hESC neuronal lineage-specific differentiation and opens the door
      to investigate human embryonic neurogenesis using the hESC model system. In this
      study, genome-scale profiling of microRNA (miRNA) differential expression
      patterns in hESC neuronal lineage-specific progression was used to identify
      molecular signatures of human embryonic neurogenesis. These in vitro
      neuroectoderm-derived human neuronal cells have acquired a neuron al identity by
      down-regulating pluripotence-associated miRNAs and inducing the expression of
      miRNAs linked to regulating human CNS development to high levels in a stage
      specific manner, including silencing of the prominent pluripotence-associated hsa
      miR-302 family and drastic expression increases of the Hox hsa-miR-10 and let-7
      miRNAs. Following transplantation, hESC-I hNuPs engrafted and yielded well
      integrated neurons at a high prevalence within neurogenic regions of the brain.
      In 3D culture, these hESC-I hNuPs proceeded to express subtype neuronal markers,
      such as dopaminergic and motor neurons, demonstrating their therapeutic potential
      for CNS repair. Our study provides critical insight into molecular neurogenesis
      in human embryonic development as well as offers an adequate human neurogenic
      cell source in high purity and large quantity for scale-up CNS regeneration.

PMID- 23543895
TI  - Development of the hypothalamic melanocortin system.
AB  - The melanocortin system is a critical component of the forebrain and hindbrain
      regulatory systems involved in energy balance. This system is composed of pro
      opiomelanocortin (POMC) neurons that act, in part, through the melanocortin-4
      receptor (MC4R). Although the importance of the melanocortin system in
      controlling feeding has been established for two decades, the understanding of
      the developmental substrates underlying POMC and MC4R neuron development and
      function has just begun to emerge. The formation of the melanocortin system
      involves several discrete developmental steps that include the birth and fate
      specification of POMC- and MC4R-containing neurons and the extension and guidance
      of POMC axons to their MC4R-expressing target nuclei. Each of these developmental
      processes appears to require specific sets of genes and developmental cues that
      include perinatal hormones. Recent evidence has also highlighted the importance
      of perinatal nutrition in controlling the ultimate architecture of the
      melanocortin system.

PMID- 23543896
TI  - Experimental evaluation of analgesic and anti-inflammatory potential of Oyster
      mushroom Pleurotus florida.
AB  - BACKGROUND: Edible mushrooms have been used as flavorful foods and as health
      nutritional supplements for several centuries. A number of bioactive molecules
      have been identified in numerous mushroom species. OBJECTIVE: To evaluate the
      analgesic and anti-inflammatory potential of Oyster Mushroom Pleurotus florida
      using various experimental models in Wistar rats. MATERIALS AND METHODS: Acute
      toxicity studies were performed whereby dose of 250 mg/ kg and 500 mg/kg was
      selected for present study, Analgesic activity was determined using hot plate
      method, tail flick method, acetic acid induced writhing and formalin induced pain
      in rats, while carrageenan was used to induce inflammation and anti-inflammatory
      studies were performed. RESULTS: HEE showed significant (P < 0.01) analgesic and
      anti-inflammatory response against all experimental models. CONCLUSION: These
      studies conclude that Pleurotus florida possesses analgesic and anti-
      inflammatory potential which might be due to presence of myochemicals like
      flavonoids, phenolics and polysaccharides.

PMID- 23543897
TI  - Metabolomic profiling of lung and prostate tumor tissues by capillary
      electrophoresis time-of-flight mass spectrometry.
AB  - Metabolic microenvironment of tumor cells is influenced by oncogenic signaling
      and tissue-specific metabolic demands, blood supply, and enzyme expression. To
      elucidate tumor-specific metabolism, we compared the metabolomics of normal and
      tumor tissues surgically resected pairwise from nine lung and seven prostate
      cancer patients, using capillary electrophoresis time-of-flight mass spectrometry
      (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon
      metabolism were also quantified. Metabolomic profiles of lung and prostate
      tissues comprised 114 and 86 metabolites, respectively, and the profiles not only
      well distinguished tumor from normal tissues, but also squamous cell carcinoma
      from the other tumor types in lung cancer and poorly differentiated tumors from
      moderately differentiated tumors in prostate cancer. Concentrations of most amino
      acids, especially branched-chain amino acids, were significantly higher in tumor
      tissues, independent of organ type, but of essential amino acids were
      particularly higher in poorly differentiated than moderately differentiated
      prostate cancers. Organ-dependent differences were prominent at the levels of
      glycolytic and tricarboxylic acid cycle intermediates and associated energy
      status. Significantly high lactate concentrations and elevated activating
      phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors
      confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based
      metabolomics combined with phosphorylated enzyme analysis for understanding
      tissue-specific tumor microenvironments, which may lead to the development of
      more effective and specific anticancer therapeutics.

PMID- 23543899
TI  - When does Iconicity in Sign Language Matter?
AB  - We examined whether iconicity in American Sign Language (ASL) enhances
      translation performance for new learners and proficient signers. Fifteen hearing
      nonsigners and 15 proficient ASL-English bilinguals performed a translation
      recognition task and a production translation task. Nonsigners were taught 28 ASL
      verbs (14 iconic; 14 non-iconic) prior to performing these tasks. Only new
      learners benefited from sign iconicity, recognizing iconic translations faster
      and more accurately and exhibiting faster forward (English-ASL) and backward (ASL
      English) translation times for iconic signs. In contrast, proficient ASL-English
      bilinguals exhibited slower recognition and translation times for iconic signs.
      We suggest iconicity aids memorization in the early stages of adult sign language
      learning, but for fluent L2 signers, iconicity interacts with other variables
      that slow translation (specifically, the iconic signs had more translation
      equivalents than the non-iconic signs). Iconicity may also have slowed
      translation performance by forcing conceptual mediation for iconic signs, which
      is slower than translating via direct lexical links.

PMID- 23543898
TI  - Association of the epithelial-to-mesenchymal transition phenotype with
      responsiveness to the p21-activated kinase inhibitor, PF-3758309, in colon cancer
      models.
AB  - The p21-activated kinase (PAK) family of serine/threonine kinases, which are
      overexpressed in several cancer types, are critical mediators of cell survival,
      motility, mitosis, transcription, and translation. In the study presented here,
      we utilized a panel of colorectal cancer (CRC) cell lines to identify potential
      biomarkers of sensitivity or resistance that may be used to individualize therapy
      to the PAK inhibitor PF-03758309. We observed a wide range of proliferative
      responses in the CRC cell lines exposed to PF-03758309, this response was
      recapitulated in other phenotypic assays such as anchorage-independent growth,
      three-dimensional (3D) tumor spheroid formation, and migration. Interestingly, we
      observed that cells most sensitive to PF-03758309 exhibited up-regulation of
      genes associated with a mesenchymal phenotype (CALD1, VIM, ZEB1) and cells more
      resistant had an up-regulation of genes associated with an epithelial phenotype
      (CLDN2, CDH1, CLDN3, CDH17) allowing us to derive an epithelial-to-mesenchymal
      transition (EMT) gene signature for this agent. We assessed the functional role
      of EMT-associated genes in mediating responsiveness to PF-3758309, by targeting
      known genes and transcriptional regulators of EMT. We observed that suppression
      of genes associated with the mesenchymal phenotype conferred resistance to PF
      3758309, in vitro and in vivo. These results indicate that PAK inhibition is
      associated with a unique response phenotype in CRC and that further studies
      should be conducted to facilitate both patient selection and rational combination
      strategies with these agents.

PMID- 23543900
TI  - Tuberculosis awareness program and associated changes in knowledge levels of
      school students.
AB  - BACKGROUND: This study aimed to assess the effectiveness of tuberculosis
      awareness program amongst school students. METHODS: This school-based
      interventional study was done on 135 secondary school students. They were
      randomly selected in field practice area of Urban Health Training Center (UHTC)
      of a private medical college in Pune city. Health awareness session on
      tuberculosis was conducted by using various visual and audiovisual aids by the
      medical college undergraduate students. A pre-test and post-proforma was filled
      before and after the session. Paired t-test was used to assess the effectiveness
      of awareness program. RESULTS: There was a highly significant (P = 0) increase in
      the knowledge of school students after the tuberculosis awareness program by
      medical undergraduate students. The mean pre-test scores were 6.31 (52.58%), and
      the mean post-test scores were 10.20 (85%). This activity also helped medical
      undergraduate students to acquire skills related to communication, working in a
      team, preparation and presentation of various visual aids for health awareness
      program; they also gained knowledge of research methodology. CONCLUSIONS: Health
      education program by medical students helped significantly to improve the
      knowledge of school students regarding tuberculosis. Thus, medical college
      students can be involved to some extent for conducting health-related behavioral
      change communication (BCC) activities in schools during their Community Medicine
      morning posting. Collaboration of private medical colleges, schools, and district
      tuberculosis units (DTUs) can be ideally achieved under public private
      partnership (PPP) for health awareness programs.

PMID- 23543901
TI  - Risk of behavioral and adaptive functioning difficulties in youth with previous
      and current sleep disordered breathing.
AB  - OBJECTIVES: To examine the rates of behavioral and adaptive functioning
      difficulties among youth who never had sleep disordered breathing (SDB), had
      remitted SDB, had incident SDB, or had persistent SDB; and to determine if there
      were increased odds of behavioral difficulties among youth with varying SDB
      histories relative to those who never had SDB. METHODS: 263 youth had valid
      polysomnography and neurobehavioral data at two time points approximately 5 years
      apart from the prospective Tucson Children's Assessment of Sleep Apnea study.
      Primary outcomes were the behavior assessment scale for children-2(nd) Edition
      parent report form (BASC-PRF) and Self-Report of Personality (SRP), and the
      Adaptive Behavior Assessment System-2(nd) Edition (ABAS-2). RESULTS: Compared to
      those who never had SDB, individuals with persistent SDB had significant odds and
      met more cutoff scores on the BASC-2-PRF externalizing problems composite (odds
      ratio [OR] 3.29; 8.92% vs. 35.3%), behavioral symptoms index (OR 6.82; 7.4% vs.
      35.3%) and Hyperactivity subscale (OR 6.82; 11.1% vs. 41.2%). Similarly, greater
      difficulties was seen for the group with persistent SDB (relative to never) on
      the ABAS-2 social domain (OR 3.39; 22% vs. 50%), and Communication (OR 4.26; 15%
      vs. 42.9%) and Self-Care subscales (OR = 2.97; 25.2% vs. 50%). Relative to youth
      who never had SDB, youth who developed SDB at Time 2 had compromised adaptive
      skills as evidenced by the BASC-2 PRF adaptive behavior composite (OR 3.34; 15.6%
      vs. 38.1%) and the ABAS-2 general adaptive composite (OR 2.83; 20.5% vs. 42.1%).
      CONCLUSIONS: Youth with current SDB exhibited hyperactivity, attention problems,
      aggressivity, lower social competency, poorer communication, and/or diminished
      adaptive skills.

PMID- 23543902
TI  - Optimal Sparse Segment Identification with Application in Copy Number Variation
      Analysis.
AB  - Motivated by DNA copy number variation (CNV) analysis based on high-density
      single nucleotide polymorphism (SNP) data, we consider the problem of detecting
      and identifying sparse short segments in a long one-dimensional sequence of data
      with additive Gaussian white noise, where the number, length and location of the
      segments are unknown. We present a statistical characterization of the
      identifiable region of a segment where it is possible to reliably separate the
      segment from noise. An efficient likelihood ratio selection (LRS) procedure for
      identifying the segments is developed, and the asymptotic optimality of this
      method is presented in the sense that the LRS can separate the signal segments
      from the noise as long as the signal segments are in the identifiable regions.
      The proposed method is demonstrated with simulations and analysis of a real data
      set on identification of copy number variants based on high-density SNP data. The
      results show that the LRS procedure can yield greater gain in power for detecting
      the true segments than some standard signal identification methods.

PMID- 23543903
TI  - Mother-son relationship as a risk factor for depressive symptoms among
      methamphetamine users.
AB  - Retrospective reports of children's relationships with their parents have been
      associated with increased risk for depressive symptoms in adulthood. This study
      examined four dimensions of the current mother-child relationship (affection,
      criticism, over-involvement, conflict) in relation to depressive symptoms in a
      sample of 270 HIV-positive men who have sex with men (MSM). Depressive symptoms
      were positively associated with overt conflict or disagreement with mothers and
      perceived over-involvement by mothers, and inversely related to frequency of
      contact with mothers. These findings suggest that clinicians who treat HIV
      positive methamphetamine-using MSM with depressive symptoms should evaluate
      issues in the mother-son relationship and consider family-based therapies as an
      adjunct to treatment.

PMID- 23543904
TI  - New Modulators for IGF-I Activity within IGF-I Processing Products.
AB  - Insulin-like growth factor I (IGF-I) is a key regulator of muscle development and
      growth. The pre-pro-peptide produced by the Igf1 gene undergoes several post
      translational processing steps to result in a secreted mature protein, which is
      thought to be the obligate ligand for the IGF-I receptor (IGF-IR). However, the
      significance of the additional forms and peptides produced from Igf1 is not
      clear. For instance, the C-terminal extensions called the E-peptides that are
      part of pro-IGF-I, have been implicated in playing roles in cell growth,
      including cell proliferation and migration and muscle hypertrophy in an IGF-IR
      independent manner. However, the activity of these peptides has been
      controversial. IGF-IR independent actions suggest the existence of an E-peptide
      receptor, yet such a protein has not been discovered. We propose a new concept:
      there is no E-peptide receptor, rather the E-peptides coordinate with IGF-I to
      modulate activity of the IGF-IR. Growing evidence reveals that the presence of an
      E-peptide alters IGF-I activity, whether as part of pro-IGF-I, or as a separate
      peptide. In this review, we will examine the past literature on IGF-I processing
      and E-peptide actions in skeletal muscle, address the previous attempts to
      separate IGF-I and E-peptide effects, propose a new model for IGF-I/E-peptide
      synergy, and suggest future experiments to test if the E-peptides truly modulate
      IGF-I activity.

PMID- 23543905
TI  - Aluminium phosphide-induced genetic and oxidative damages in vitro: attenuation
      by Laurus nobilis L. leaf extract.
AB  - OBJECTIVE: The present investigation was undertaken to assess the protective
      effect of Laurus nobilis leaf extract (LNE) against aluminum phosphide (AIP)
      induced genotoxic and oxidative damages stress in cultured human blood cells in
      the presence of a metabolic activator (S9 mix). MATERIALS AND METHODS: Sister
      chromatid exchange (SCE) and chromosome aberration (CA) assays were used to
      assess AlP-induced genotoxicity and to establish the protective effects of LNE.
      In addition, we determined total antioxidant capacity (TAC) and total oxidative
      status (TOS) levels in AlP and LNE treated cultures for biomonitoring the
      oxidative alterations. RESULTS: There was significant increases (P < 0.05) in
      both SCE and CA frequencies of cultures treated with AlP as compared to controls.
      Our results also showed that AlP (58 mg/l) caused oxidative stress by altering
      TAC and TOS levels. However, co-application of LNE (25, 50, 100 and 200 mg/l) and
      AlP resulted in decreases of SCE, CA rates and TOS level and increases of TAC
      level as compared to the group treated with AlP alone. CONCLUSION: The preventive
      role of LNE in alleviating AlP-induced DNA and oxidative damages was indicated
      for the first time in the present study.

PMID- 23543906
TI  - Synthesis and anticancer evaluation of novel 3,5-diaryl-thiazolo[4,5-d]pyrimidin
      2-one derivatives.
AB  - The 2-oxo analogs of thiazolo[4,5-d]pyrimidine-2-thiones were prepared to study
      their cytotoxic activity. Five of the newly synthesized compounds were selected
      by the National Cancer Institute (Bethesda, MD, USA) for a primary in vitro
      antitumor assay. 7-Chloro-3,5-diphenyl-thiazolo[4,5-d]pyrimidin-2-one (5a) proved
      to be the most active one among the screened derivatives and was further
      evaluated in the full panel of 60 cell lines at five different concentrations.
      The structures of compounds were determined by IR, 1H-NMR, 13C-NMR, X-ray, and
      elemental analysis.

PMID- 23543907
TI  - Neurophysiological, metabolic and cellular compartments that drive neurovascular
      coupling and neuroimaging signals.
AB  - Complete understanding of the mechanisms that coordinate work and energy supply
      of the brain, the so called neurovascular coupling, is fundamental to
      interpreting brain energetics and their influence on neuronal coding strategies,
      but also to interpreting signals obtained from brain imaging techniques such as
      functional magnetic resonance imaging. Interactions between neuronal activity and
      cerebral blood flow regulation are largely compartmentalized. First, there exists
      a functional compartmentalization in which glutamatergic peri-synaptic activity
      and its electrophysiological events occur in close proximity to vascular
      responses. Second, the metabolic processes that fuel peri-synaptic activity are
      partially segregated between glycolytic and oxidative compartments. Finally,
      there is cellular segregation between astrocytic and neuronal compartments, which
      has potentially important implications on neurovascular coupling. Experimental
      data is progressively showing a tight interaction between the products of energy
      consumption and neurotransmission-driven signaling molecules that regulate blood
      flow. Here, we review some of these issues in light of recent findings with
      special attention to the neuron-glia interplay on the generation of neuroimaging
      signals.

PMID- 23543909
TI  - Multinight recording and analysis of continuous positive airway pressure airflow
      in the home for titration and management of sleep disordered breathing.
AB  - OBJECTIVES: The authors examined magnitude/variability of residual sleep
      disordered breathing (SDB) at pressures around the therapeutic continuous
      positive airway pressure (CPAP), and described a multinight approach to CPAP
      titration/retitration consisting of recording airflow and summarizing SDB over
      multiple nights at multiple pressures and choosing an optimal pressure from these
      summarized data. DESIGN: Prospective, single-center nonblinded study. PATIENTS:
      Ten female/18 male patients with obstructive sleep apnea-hypopnea syndrome
      (OSAHS) (respiratory disturbance index [RDI] 67/h), 17 newly-initiated, 11
      chronic CPAP users. INTERVENTIONS: A custom CPAP device (Fisher & Paykel
      Healthcare) recording airflow and pre-programmed to vary CPAP between 2-3 cm H2O
      below and 1-2 cm H2O above prescription pressure as determined by a full
      laboratory titration. RESULTS: Airflow and pressure continuously recorded for
      multiple nights (15.9 +/- 5.1 nights) at four to seven different pressures in
      each patient. SDB events manually scored from the airflow as apnea (airflow
      reduction > 90%), hypopnea (airflow reduction > 30% lasting 10 to 120 sec with
      inspira-tory flow limitation [IFL]) and runs of sustained IFL > 2 min identified.
      RDI = (apnea + hypopnea)/total sleep time calculated for each night and an
      obstruction index, including sustained IFL, also was calculated.
      PressureMultinight was obtained for each patient from multiple nights of data
      using two mathematical techniques. Night-to-night variability of SDB indices was
      low in some patients and significant in others. PressureMultinight could be
      determined in 17 of 28 patients and was similar to the in-laboratory pressure.
      CONCLUSIONS: This study showed that recording multiple nights of CPAP airflow in
      the home and analyzing these data for residual SDB provided useful information,
      including the possibility of determining a therapeutic prescription for fixed
      CPAP in most patients and identification of others with significant physiologic
      variability of SDB.

PMID- 23543908
TI  - Safety of Anti-Diabetic Therapies on Bone.
AB  - Osteoporosis and diabetic disease have reached epidemic proportion and create
      significant public health concerns. The prevalence of these diseases is alarming,
      and indicates that in the US, 50% of elderly individuals are osteoporotic and
      almost 20% of population has either diabetic or prediabetic conditions (Centers
      for Disease Control and Prevention; http://www.cdc.gov). Osteoporosis and
      diabetes share many features including genetic predispositions and molecular
      mechanisms. The linkage between these two chronic diseases, which stems from
      overlapping molecular controls involved in bone homeostasis and energy
      metabolism, creates a possibility that certain anti-diabetic therapies may affect
      bone. This concurs with recent findings indicating that bone status is closely
      linked to regulation of energy metabolism and insulin sensitivity. Indeed, bone
      and energy homeostasis are under the control of the same regulatory factors,
      including insulin, peroxisome proliferator activated receptor gamma (PPARgamma),
      gastrointestinal hormones such as glucose inhibitory protein (GIP) and glucagon
      inhibitory peptide (GLP), and bone derived hormone osteocalcin. These factors and
      related mechanisms control glucose homeostasis and fatty acids metabolism in fat
      tissue, pancreas and intestine, which are pharmacological targets for anti
      diabetic therapies. The same factors contribute to the bone quality by their
      effect on bone cell differentiation and bone remodeling process. This implies
      that bone should be considered as a vital target for therapies which modulate
      energy metabolism. This review is summarizing available data on the skeletal
      effects of clinically approved anti-diabetic therapies.

PMID- 23543910
TI  - Using Logic Analysis to Evaluate Knowledge Transfer Initiatives: The Case of the
      Research Collective on the Organization of Primary Care Services.
AB  - Models that shift more responsibility onto researchers for the process of
      incorporating research results into decision-making have greatly gained in
      popularity during the past two decades. This shift has created a new area of
      research to identify the best ways to transfer academic results into the
      organizational and political arenas. However, evaluating the utilization of
      information coming out of a knowledge transfer (KT) initiative remains an
      enormous challenge. This article demonstrates how logic analysis has proven to be
      a useful evaluation method to assess the utilization potential of KT initiatives.
      We present the case of the evaluation of the Research Collective on the
      Organization of Primary Care Services, an innovative experiment in knowledge
      synthesis and transfer. The conclusions focus not only on the utilization
      potential of results coming out of the Research Collective, but also on the
      theoretical framework used, in order to facilitate its application to the
      evaluation of other knowledge transfer initiatives.

PMID- 23543911
TI  - Multifunctional hybrid silica nanoparticles for controlled doxorubicin loading
      and release with thermal and pH dually response.
AB  - Controlled drug loading and release into tumor cells to increase the
      intracellular drug concentration is a major challenge for cancer therapy due to
      resistance and inefficient cellular uptake. Here a temperature and pH dually
      responsive PNiPAM/AA@SiO2 core-shell particles with internal controlled release
      were designed and fabricated for efficient cancer treatment, which could
      recognize the intrinsic pH differences between cancers and normal tissues. Upon
      lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO2
      nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin
      was quickly released. Comparing with common mesoporous silica particles (MSNs),
      this core-shell particle has more uniform size and better dispersity. In
      addition, dried PNiPAM/AA@SiO2 nanoparticles could be easily redispersed in
      distilled water. The in vitro cell culture experiments showed that not only
      PNiPAM/AA@SiO2 particles were more biocompatible and lower cytotoxic than MSN,
      but also DOX@PNiPAM/AA@SiO2 had higher drug releasing efficiency in the lysosomes
      and stronger inhibitory effect on tumor cell growth than DOX@MSN. All these
      features indicated that PNiPAM/AA@SiO2 particles have great potential in therapy
      applications.

PMID- 23543913
TI  - Translational biomarker discovery in clinical metabolomics: an introductory
      tutorial.
AB  - Metabolomics is increasingly being applied towards the identification of
      biomarkers for disease diagnosis, prognosis and risk prediction. Unfortunately
      among the many published metabolomic studies focusing on biomarker discovery,
      there is very little consistency and relatively little rigor in how researchers
      select, assess or report their candidate biomarkers. In particular, few studies
      report any measure of sensitivity, specificity, or provide receiver operator
      characteristic (ROC) curves with associated confidence intervals. Even fewer
      studies explicitly describe or release the biomarker model used to generate their
      ROC curves. This is surprising given that for biomarker studies in most other
      biomedical fields, ROC curve analysis is generally considered the standard method
      for performance assessment. Because the ultimate goal of biomarker discovery is
      the translation of those biomarkers to clinical practice, it is clear that the
      metabolomics community needs to start "speaking the same language" in terms of
      biomarker analysis and reporting-especially if it wants to see metabolite markers
      being routinely used in the clinic. In this tutorial, we will first introduce the
      concept of ROC curves and describe their use in single biomarker analysis for
      clinical chemistry. This includes the construction of ROC curves, understanding
      the meaning of area under ROC curves (AUC) and partial AUC, as well as the
      calculation of confidence intervals. The second part of the tutorial focuses on
      biomarker analyses within the context of metabolomics. This section describes
      different statistical and machine learning strategies that can be used to create
      multi-metabolite biomarker models and explains how these models can be assessed
      using ROC curves. In the third part of the tutorial we discuss common issues and
      potential pitfalls associated with different analysis methods and provide readers
      with a list of nine recommendations for biomarker analysis and reporting. To help
      readers test, visualize and explore the concepts presented in this tutorial, we
      also introduce a web-based tool called ROCCET (ROC Curve Explorer & Tester,
      http://www.roccet.ca). ROCCET was originally developed as a teaching aid but it
      can also serve as a training and testing resource to assist metabolomics
      researchers build biomarker models and conduct a range of common ROC curve
      analyses for biomarker studies.

PMID- 23543914
TI  - Study of interaction of tramadol with amlodipine in mice.
AB  - OBJECTIVE: To study a possible interaction between tramadol, an opioid analgesic
      and amlodipine, a dihydropyridine calcium channel blocker with proposed
      antinociceptive property. MATERIALS AND METHODS: Albino mice of Haffkine strain
      were used for the study. The experiment was carried out using tail-flick method.
      Different doses of tramadol (50 mg/kg, 22.8 mg/kg and 10 mg/kg) were administered
      intraperitoneally to select the nonanalgesic dose. The animals were treated with
      different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg, 3.5 mg/kg) to study its
      antinociceptive action. Combination of different doses of both the drugs were
      administered to study antinociceptive effect of the combination. RESULTS:
      Tramadol, showed dose dependent antinociception which persisted for entire two
      hours of the study period. Antinociceptive action was seen with amlodipine at a
      dose of 3.5 mg/kg. Different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg) in
      combination with the nonanalgesic dose of tramadol (10 mg/kg) produced a
      significant enhancement of antinociceptive effect of tramadol. Combination of 3.5
      mg/kg dose of amlodipine with nonanalgesic dose of tramadol (10 mg/kg) further
      enhances antinociceptive activity. CONCLUSION: It is concluded that combination
      of amlodipine, a N - type calcium channel blocker, with tramadol produce
      significant enhancement of antinociceptive activity of tramadol.

PMID- 23543912
TI  - Serotonin and the regulation of mammalian energy balance.
AB  - Maintenance of energy balance requires regulation of the amount and timing of
      food intake. Decades of experiments utilizing pharmacological and later genetic
      manipulations have demonstrated the importance of serotonin signaling in this
      regulation. Much progress has been made in recent years in understanding how
      central nervous system (CNS) serotonin systems acting through a diverse array of
      serotonin receptors impact feeding behavior and metabolism. Particular attention
      has been paid to mechanisms through which serotonin impacts energy balance
      pathways within the hypothalamus. How upstream factors relevant to energy balance
      regulate the release of hypothalamic serotonin is less clear, but work addressing
      this issue is underway. Generally, investigation into the central serotonergic
      regulation of energy balance has had a predominantly "hypothalamocentric" focus,
      yet non-hypothalamic structures that have been implicated in energy balance
      regulation also receive serotonergic innervation and express multiple subtypes of
      serotonin receptors. Moreover, there is a growing appreciation of the diverse
      mechanisms through which peripheral serotonin impacts energy balance regulation.
      Clearly, the serotonergic regulation of energy balance is a field characterized
      by both rapid advances and by an extensive and diverse set of central and
      peripheral mechanisms yet to be delineated.

PMID- 23543915
TI  - Rhythm, movement, and autism: using rhythmic rehabilitation research as a model
      for autism.
AB  - Recently, there has been increased focus on movement and sensory abnormalities in
      autism spectrum disorders (ASD). This has come from research demonstrating
      cortical and cerebellar differences in autism, with suggestion of early
      cerebellar dysfunction. As evidence for an extended profile of ASD grows, there
      are vast implications for treatment and therapy for individuals with autism.
      Persons with autism are often provided behavioral or cognitive strategies for
      navigating their environment; however, these strategies do not consider
      differences in motor functioning. One accommodation that has not yet been
      explored in the literature is the use of auditory rhythmic cueing to improve
      motor functioning in ASD. The purpose of this paper is to illustrate the
      potential impact of auditory rhythmic cueing for motor functioning in persons
      with ASD. To this effect, we review research on rhythm in motor rehabilitation,
      draw parallels to motor dysfunction in ASD, and propose a rationale for how
      rhythmic input can improve sensorimotor functioning, thereby allowing individuals
      with autism to demonstrate their full cognitive, behavioral, social, and
      communicative potential.

PMID- 23543916
TI  - Relations between Preschool Attention Span-Persistence and Age 25 Educational
      Outcomes.
AB  - This study examined relations between children's attention span-persistence in
      preschool and later school achievement and college completion. Children were
      drawn from the Colorado Adoption Project using adopted and non-adopted children
      (N = 430). Results of structural equation modeling indicated that children's age
      4 attention span-persistence significantly predicted math and reading achievement
      at age 21 after controlling for achievement levels at age 7, adopted status,
      child vocabulary skills, gender, and maternal education level. Relations between
      attention span-persistence and later achievement were not fully mediated by age 7
      achievement levels. Logistic regressions also revealed that age 4 attention span
      persistence skills significantly predicted the odds of completing college by age
      25. The majority of this relationship was direct and was not significantly
      mediated by math or reading skills at age 7 or age 21. Specifically, children who
      were rated one standard deviation higher on attention span-persistence at age 4
      had 48.7% greater odds of completing college by age 25. Discussion focuses on the
      importance of children's early attention span-persistence for later school
      achievement and educational attainment.

PMID- 23543917
TI  - RNA blood levels of osteopontin splice variants are cancer markers.
AB  - PURPOSE: Despite a sizeable and continuously growing literature on osteopontin
      and cancer the molecule has not yet found entry into clinical diagnostics. Our
      identification of spliced variants that are more specific for cancer than the
      full-length transcript has opened new possibilities for reaching this goal.
      METHODS: Here we have developed a real-time RT-PCR blood test and evaluated it in
      a pilot study of breast, lung, pancreatic, gynecologic, and other cancers,
      compared to non-cancer controls. RESULTS: Osteopontin-b was increased in lung
      cancers and pancreatic cancers. When applying a cutoff of 2 standard deviations
      above normal, elevation in osteopontin-b transcripts detected over 40% of lung
      cancers. Osteopontin-c was increased in gynecologic and pancreatic cancers.
      Elevation in osteopontin-c of 2 standard deviations above the normal mean value
      also detected a fraction of breast cancers and lung cancers, suggesting
      heterogeneity within those types of tumors. Specifically, breast carcinomas were
      associated with significantly higher levels of osteopontin-c mRNA in the blood
      than carcinomas in situ. In lung cancer patients, the osteopontin-c blood RNA
      levels had an increasing trend with tumor grade. CONCLUSIONS: Osteopontin-b and 
      c in the blood are biomarkers for distinct cancers. Our investigations may have
      bearing on cancer screening and diagnosis.

PMID- 23543918
TI  - When interference helps: increasing executive load to facilitate deception
      detection in the concealed information test.
AB  - The possibility to enhance the detection efficiency of the Concealed Information
      Test (CIT) by increasing executive load was investigated, using an interference
      design. After learning and executing a mock crime scenario, subjects underwent
      three deception detection tests: an RT-based CIT, an RT-based CIT plus a
      concurrent memory task (CITMem), and an RT-based CIT plus a concurrent set
      shifting task (CITShift). The concealed information effect, consisting in
      increased RT and lower response accuracy for probe items compared to irrelevant
      items, was evidenced across all three conditions. The group analyses indicated a
      larger difference between RTs to probe and irrelevant items in the dual-task
      conditions, but this difference was not translated in a significantly increased
      detection efficiency at an individual level. Signal detection parameters based on
      the comparison with a simulated innocent group showed accurate discrimination for
      all conditions. Overall response accuracy on the CITMem was highest and the
      difference between response accuracy to probes and irrelevants was smallest in
      this condition. Accuracy on the concurrent tasks (Mem and Shift) was high, and
      responses on these tasks were significantly influenced by CIT stimulus type
      (probes vs. irrelevants). The findings are interpreted in relation to the
      cognitive load/dual-task interference literature, generating important insights
      for research on the involvement of executive functions in deceptive behavior.

PMID- 23543919
TI  - Retrospective analysis of Steven Johnson syndrome and toxic epidermal necrolysis
      over a period of 5 years from northern Karnataka, India.
AB  - OBJECTIVE: Cutaneous drug reactions are the most common type of adverse drug
      reactions. Adverse cutaneous drug reactions form 2-3% of the hospitalized
      patients. 2% of these are potentially serious. This study aims to detect the
      drugs commonly implicated in Steven Johnson Syndrome-Toxic Epidermal Necrosis
      (SJS-TEN). MATERIALS AND METHODS: A retrospective analysis was done in all
      patients admitted in the last five years in SDM hospital with the diagnosis of
      SJS-TEN. RESULTS: A total of 22 patients with SJS-TEN were studied. In 11
      patients anti-epileptics was the causal drug and in 7, anti-microbials was the
      causal drug. Recovery was much faster in case of anti epileptics induced SJS-TEN
      as compared to that induced by ofloxacin. CONCLUSION: SJS-TEN induced by
      ofloxacin has a higher morbidity and mortality compared to anti convulsants.

PMID- 23543920
TI  - Local histograms and image occlusion models.
AB  - The local histogram transform of an image is a data cube that consists of the
      histograms of the pixel values that lie within a fixed neighborhood of any given
      pixel location. Such transforms are useful in image processing applications such
      as classification and segmentation, especially when dealing with textures that
      can be distinguished by the distributions of their pixel intensities and colors.
      We, in particular, use them to identify and delineate biological tissues found in
      histology images obtained via digital microscopy. In this paper, we introduce a
      mathematical formalism that rigorously justifies the use of local histograms for
      such purposes. We begin by discussing how local histograms can be computed as
      systems of convolutions. We then introduce probabilistic image models that can
      emulate textures one routinely encounters in histology images. These models are
      rooted in the concept of image occlusion. A simple model may, for example,
      generate textures by randomly speckling opaque blobs of one color on top of blobs
      of another. Under certain conditions, we show that, on average, the local
      histograms of such model-generated-textures are convex combinations of more basic
      distributions. We further provide several methods for creating models that meet
      these conditions; the textures generated by some of these models resemble those
      found in histology images. Taken together, these results suggest that histology
      textures can be analyzed by decomposing their local histograms into more basic
      components. We conclude with a proof-of-concept segmentation-and-classification
      algorithm based on these ideas, supported by numerical experimentation.

PMID- 23543922
TI  - The promise of stem cell technology.

PMID- 23543921
TI  - Comparative proteomics of chloroplasts envelopes from bundle sheath and mesophyll
      chloroplasts reveals novel membrane proteins with a possible role in c4-related
      metabolite fluxes and development.
AB  - As the world population grows, our need for food increases drastically. Limited
      amounts of arable land lead to a competition between food and fuel crops, while
      changes in the global climate may impact future crop yields. Thus, a second
      "green revolution" will need a better understanding of the processes essential
      for plant growth and development. One approach toward the solution of this
      problem is to better understand regulatory and transport processes in C4 plants.
      C4 plants display an up to 10-fold higher apparent CO2 assimilation and higher
      yields while maintaining high water use efficiency. This requires differential
      regulation of mesophyll (M) and bundle sheath (BS) chloroplast development as
      well as higher metabolic fluxes of photosynthetic intermediates between cells and
      particularly across chloroplast envelopes. While previous analyses of overall
      chloroplast membranes have yielded significant insight, our comparative
      proteomics approach using enriched BS and M chloroplast envelopes of Zea mays
      allowed us to identify 37 proteins of unknown function that have not been seen in
      these earlier studies. We identified 280 proteins, 84% of which are
      known/predicted to be present in chloroplasts. Seventy-four percent have a known
      or predicted membrane association. Twenty-one membrane proteins were 2-15 times
      more abundant in BS cells, while 36 of the proteins were more abundant in M
      chloroplast envelopes. These proteins could represent additional candidates of
      proteins essential for development or metabolite transport processes in C4
      plants. RT-PCR confirmed differential expression of 13 candidate genes.
      Chloroplast association for seven proteins was confirmed using YFP/GFP labeling.
      Gene expression of four putative transporters was examined throughout the leaf
      and during the greening of leaves. Genes for a PIC-like protein and an ER-AP-like
      protein show an early transient increase in gene expression during the transition
      to light. In addition, PIC gene expression is increased in the immature part of
      the leaf and was lower in the fully developed parts of the leaf, suggesting a
      need for/incorporation of the protein during chloroplast development.

PMID- 23543923
TI  - An ethicist's commentary on the pharmaceutical supply house.

PMID- 23543924
TI  - Transabdominal ultrasonographic findings in goats with paratuberculosis.
AB  - This study describes the transabdominal ultrasonographic findings in 54 goats
      with confirmed Johne's disease (JD). Compared with the control group (0.8 +/- 0.4
      mm thick), the test group presented with mild (2.8 +/- 0.2 mm), moderate (4.2 +/-
      0.4 mm), and severe (6.9 +/- 1.1 mm) thickening of the intestinal wall. The most
      outstanding ultrasonographic findings were pronounced enlargement of the
      mesenteric lymph nodes in 49 goats. In 36 goats, the enlarged lymph nodes showed
      a hypoechoic cortex and a hyperechoic medulla. In 7 goats, the cortex and medulla
      were hypoechoic. In 5 goats, the cortex and the medulla could not be
      differentiated. In the remaining cases, the cortex and medulla contained small
      hypoechoic lesions. Necropsy findings included enlarged mesenteric lymph nodes in
      52 goats and thickening of the small intestinal wall in 30 goats. Compared with
      the postmortem results, the antemortem ultrasound sensitivity in detecting
      intestinal wall thickness and enlarged mesenteric lymph nodes was 80% and 94%,
      respectively.

PMID- 23543925
TI  - Prevalence of contagious mastitis pathogens in bulk tank milk in Quebec.
AB  - The objective of this study was to estimate the prevalence of mycoplasma,
      Staphylococcus aureus, and Streptococcus agalactiae in bulk tank milk (BTM) in
      Quebec dairy herds. BTM was sampled 3 times a month in 117 randomly selected
      dairy herds. Samples were submitted for S. aureus, S. agalactiae, and mycoplasma
      and for direct mycoplasma detection by polymerase chain reaction (PCR).
      Mycoplasma spp. was identified at least once in 3 herds (2.6%) by primary culture
      and/or PCR and in 4 herds (3.4%) by enrichment culture and/or PCR. Staphylococcus
      aureus was isolated at least once in 99 (84.6%) and 112 (95.7%) herds in primary
      culture and after enrichment, respectively. Streptococcus agalactiae was isolated
      at least once in 9 (7.7%) and 10 (8.6%) herds in primary culture and after
      enrichment, respectively. Herd prevalence of mycoplasma was similar to that
      previously reported in Canada. Staphylococcus aureus is still by far the most
      important contagious mastitis pathogen.

PMID- 23543926
TI  - Development of osteochondrosis in Lusitano foals: a radiographic study.
AB  - This study aimed to detect, by radiographic examination, the evolution of
      osteochondral lesions in the tarsocrural and femoropatellar joints of Lusitano
      foals. Within 1 month of age, 76.08% of foals had radiographic signs of
      osteochondrosis, but only 16.20% had lesions at 18 months. The radiographic signs
      resolved by 5 mo of age in most foals, but some cases that involved either joint,
      were not resolved until 12 mo of age. It is thought that the "age of no return"
      is 5 mo for the tarsocrural and 8 mo for the femoropatellar joint but this study
      demonstrated regression of osteochondral lesions in both joints of Lusitano foals
      up to 12 months of age.

PMID- 23543927
TI  - Indirect magnetic resonance lymphography of the head and neck of dogs using
      Gadofluorine M and a conventional gadolinium contrast agent: a pilot study.
AB  - The purpose of this pilot study was to evaluate lymph node enhancement with an
      indirect magnetic resonance (MR) lymphography technique using 2 different
      contrast agents in the head and neck region of healthy dogs. Five dogs were
      imaged at various times after intradermal injection of gadoversetamide and
      Gadofluorine M (minimum of 1 week apart) in the right and left mandibular,
      temporal, and lateral neck regions. We observed consistent progressive
      enhancement with time in the mandibular, retropharyngeal, and superficial
      cervical lymph nodes. The node enhancement was comparable for both contrast
      agents. Contrast enhancement of the parotid lymph nodes was not seen. We conclude
      that this technique of indirect MR lymphography using either agent could be used
      to identify those lymph nodes at highest risk of metastatic disease in dogs with
      cancer, and to guide staging and treatment.

PMID- 23543928
TI  - Seroprevalence of canine influenza virus (H3N8) in Iditarod racing sled dogs.
AB  - We conducted a cross-sectional convenience sampling study of dogs racing in the
      2010 Iditarod to determine the seroprevalence of canine influenza virus (CIV) in
      the sled dog population. Questionnaires were completed detailing medical and CIV
      vaccination history, kennel size and location, travel history, and social
      interactions for each team. A total of 399 dogs were tested for CIV antibodies by
      hemagglutination inhibition assay. None of these, including 39 samples from dogs
      reported as CIV vaccinated, were seropositive for CIV antibodies. All of the
      vaccinated dogs were also negative on virus microneutralization assay. Risk
      factors for CIV seropositivity could not be determined due to a lack of positive
      samples. This is the first published study investigating the prevalence of CIV in
      sled dogs and additional studies are warranted to assess CIV infection among
      racing sled dogs and to evaluate the ecology of CIV and the vaccine efficacy in
      this population of dogs.

PMID- 23543929
TI  - Comparison of radiographic osteoarthritis scores in dogs less than 24 months or
      greater than 24 months following tibial plateau leveling osteotomy.
AB  - Radiographic osteoarthritis scores were determined in 60 dogs up to 3 years
      following tibial plateau leveling osteotomy. Radiographs taken immediately
      following surgery and at long-term follow-up 1 to 3 years later were evaluated by
      2 certified radiologists using a modified 32-point osteoarthritis scale. Changes
      in osteoarthritis scores were evaluated by paired t-tests and regression
      analysis. Sub-groups of dogs were formed to evaluate if osteoarthritis scores
      changed differently for follow-up periods of < 24 months compared with those > 24
      months. There was a significant increase in osteoarthritis score from post
      operative to follow-up evaluations for all dogs studied. Regression analysis of
      the relationship of months after surgery to change in osteoarthritis score was
      not significant. These results indicate that osteoarthritis did progress
      following tibial plateau leveling osteotomy, but not in a linear fashion over
      time.

PMID- 23543930
TI  - Paraneoplastic hypercalcemia in a dog with thyroid carcinoma.
AB  - This case report describes a dog with thyroid carcinoma and paraneoplastic
      hypercalcemia. Following thyroidectomy the dog became hypocalcemic and required
      supplementation with calcitriol and calcium carbonate. During the following 2
      years, attempts to reduce the supplementation resulted in hypocalcemia. The dog
      died from renal failure with no evidence of thyroid carcinoma.

PMID- 23543931
TI  - Female pseudo-hermaphroditism with cloacal malformation and related anomalies in
      a dog.
AB  - A 7-month-old intact female German shepherd dog was presented with recurrent
      urinary tract infections and incontinence, ambiguous external genitalia (enlarged
      vulva containing a penis), and an anovestibular fistula. Anatomical structures,
      histopathology, and karyotyping supported a diagnosis of female pseudo
      hermaphrodite, hypothesized to be a result of in utero androgenization with
      consequential cloacal malformation.

PMID- 23543932
TI  - Atypical pneumonia associated with a Mycoplasma isolate in a kitten.
AB  - An atypical case of Mycoplasma pneumonia with an unusual radiographic and
      computed tomographic pattern was diagnosed in a Siamese kitten. The cat showed no
      response to broad-spectrum antibiotic therapy including enrofloxacin. The
      administration of doxycycline led to a dramatic clinical and radiographic
      improvement.

PMID- 23543933
TI  - Total venous inflow occlusion and pericardial auto-graft reconstruction for right
      atrial hemangiosarcoma resection in a dog.
AB  - A sizeable right atrial hemangiosarcoma in a 6-year-old Bordeaux dog, World
      Health Organization (WHO) stage 2, was excised using total venous inflow
      occlusion. The defect was restored with a non-vascularized pericardial auto
      graft. The dog had a disease-free interval of 7 mo. The dog was euthanized 9
      months later, at which time there were distant metastases but no indication of
      local recurrence.

PMID- 23543934
TI  - Time to clearance of mycoplasma mastitis: the effect of management factors
      including milking time hygiene and preferential culling.
AB  - Factors associated with time to clearance of mycoplasma mastitis were studied in
      18 dairy cattle herds. Most herds cleared mycoplasma mastitis within 1 month; <
      50% of the herds culled diseased cows preferentially, yet culling was not
      associated with hastened clearance. Other known mastitis biosecurity and
      management practices were not associated with clearance time.

PMID- 23543935
TI  - Anthrax and the taiga.

PMID- 23543936
TI  - The art of veterinary practice: a personal approach to praise and criticism.

PMID- 23543937
TI  - Racial Differences in Exposure and Reactivity to Daily Family Stressors.
AB  - Using data from the National Study of Daily Experiences (NSDE), this study
      examined racial differences in exposure and reactivity to daily stressors
      involving family members. Respondents included African American and European
      American adults aged 34 to 84 (N = 1,931) who participated in 8 days of daily
      interviews where they reported on daily stressors, affect, and physical health
      symptoms. Results revealed racial similarities in family stressor exposure. Both
      races were also emotionally reactive to family arguments and family network
      events (i.e., events that happen to a family member), whereas African Americans
      were more physically reactive to family arguments. For African Americans,
      reactivity to family arguments endured; the increased negative affect and
      physical symptoms associated with family arguments lasted into the next day.
      Findings provide evidence for racial similarities and differences, suggesting
      that family relationships are universally stressful, whereas the negative effects
      of family stressors are more enduring among African Americans.

PMID- 23543938
TI  - Illumination with a Dim Bulb? What do social scientists learn by employing
      qualitative data analysis software (QDAS) in the service of multi-method designs?
AB  - Although there has been much optimistic discussion of integrating quantitative
      and qualitative findings into sociological analysis, there remains a gap
      regarding the application of mixed approaches. We examine the potential gains and
      pitfalls of such integration in the context of the growing analytic power of
      contemporary qualitative data analysis software (QDAS) programs. We illustrate
      the issues with our own research in a mixed-methods project examining low
      fertility in Italy, a project that combines analysis of large nationally
      representative survey data with qualitative in-depth interviews with women across
      four (4) cities in Italy. Despite the enthusiasm for mixed-methods research, the
      available software appears to be underutilized. In addition, we suggest that the
      sociological research community will want to address several conceptual and
      inferential issues with these approaches.

PMID- 23543939
TI  - SCREENING FOR AND PREVALENCE OF HIV AND HEPATITIS C AMONG AN OUTPATIENT URBAN
      SAMPLE OF PEOPLE WITH SERIOUS MENTAL ILLNESS AND CO-OCCURRING SUBSTANCE ABUSE.
AB  - BACKGROUND: To assess rates of screening and testing of HIV and HCV among those
      with serious mental illness and co-occurring substance use disorders. METHODS:
      One hundred fifty-three people with serious mental illness and cooccurring
      substance use disorders completed measures and were screened for HIV and HCV.
      RESULTS: Six percent were HIV positive and 25% were HCV positive. Almost a
      quarter reported a history of injection drug use and 86% reported a history of
      unprotected sexual encounters. Compared to those without a diagnosis of Hepatitis
      C, those diagnosed with Hepatitis C were significantly more likely to have a
      sexually transmitted infection, (p = 0.01), have a lifetime history of injection
      drug use, (p < 0.001), and a lifetime history of sniffing drugs, (p = 0.01).
      CONCLUSIONS: Given the high levels of infection of HIV and HCV and high levels of
      transmission risk factors efforts to improve screening and provide risk reduction
      counseling are warranted.

PMID- 23543940
TI  - SMART Design Issues and the Consideration of Opposing Outcomes: Discussion of
      "Evaluation of Viable Dynamic Treatment Regimes in a Sequentially Randomized
      Trial of Advanced Prostate Cancer" by by Wang, Rotnitzky, Lin, Millikan, and
      Thall.

PMID- 23543941
TI  - Integrated teaching in medicine - Indian scene.

PMID- 23543942
TI  - Introducing team based learning in undergraduate pharmacology.

PMID- 23543943
TI  - Normative data for arterial blood gas and electrolytes in anesthetized rats.

PMID- 23543944
TI  - Updates on clinical pharmacology of dengue.

PMID- 23543945
TI  - Taxing essential medicines is inhuman.

PMID- 23543946
TI  - 2-Seleno-1-alkylbenzimidazoles and their Diselenides: Synthesis and Structural
      Characterization of a 2-Seleno-1-methylbenzimidazole Complex of Mercury.
AB  - 2-Seleno-1-methylbenzimidazole, H(sebenzimMe), can be synthesized from 1
      methylbenzimidazole by sequential treatment with (i) BunLi, (ii) elemental
      selenium and (iii) HCl(aq). This method is also applicable to the synthesis of 2
      seleno-1-t-butylbenzimidazole, H(sebenzimBut ). Single crystal X-ray diffraction
      and NMR spectroscopic data demonstrate that H(sebenzimMe) and H(sebenzimBut )
      exist as the selone rather than the selenol tautomers, which is in accord with
      the results of density functional theory (B3LYP) calculations. The data also
      indicate that the selone is best represented as a C+-Se- zwitterion rather than
      as a C=Se doubly bonded species. Aerobic oxidation of H(sebenzimMe) and
      H(sebenzimBut ) in the presence of Et3N yields the diselenides, (sebenzimMe)2 and
      (sebenzimBut )2. In addition, H(sebenzimMe) reacts with HgCl2 to give
      [H(sebenzimMe)]2HgCl2, the first structurally characterized example of a 2-seleno
      1-alkylimidazole mercury complex.

PMID- 23543947
TI  - Using Crash Data to Develop Simulator Scenarios for Assessing Novice Driver
      Performance.
AB  - Teenage drivers are at their highest crash risk in their first 6 months or first
      1,000 mi of driving. Driver training, adult-supervised practice driving, and
      other interventions are aimed at improving driving performance in novice drivers.
      Previous driver training programs have enumerated thousands of scenarios, with
      each scenario requiring one or more skills. Although there is general agreement
      about the broad set of skills needed to become a competent driver, there is no
      consensus set of scenarios and skills to assess whether novice drivers are likely
      to crash or to assess the effects of novice driver training programs on the
      likelihood of a crash. The authors propose that a much narrower, common set of
      scenarios can be used to focus on the high-risk crashes of young drivers. Until
      recently, it was not possible to identify the detailed set of scenarios that were
      specific to high-risk crashes. However, an integration of police crash reports
      from previous research, a number of critical simulator studies, and a nationally
      representative database of serious teen crashes (the National Motor Vehicle Crash
      Causation Survey) now make identification of these scenarios possible. In this
      paper, the authors propose this novel approach and discuss how to create a common
      set of simulated scenarios and skills to assess novice driver performance and the
      effects of training and interventions as they relate to high-risk crashes.

PMID- 23543948
TI  - Hepatocyte apoptosis in dairy cattle during the transition period.
AB  - The objective of this study was to investigate hepatocyte apoptosis in dairy cows
      during the transition period. Four clinically healthy, pregnant dairy cattle were
      used. The cows had no clinical diseases throughout this study. Blood samples were
      collected and livers were biopsied from the cows at 3 different times: 3 weeks
      before expected partition (wk -3); during parturition (wk 0), and 3 weeks (wk +3)
      after parturition. The damage to deoxyribonucleic acid (DNA) caused by
      hepatocytes was evaluated by comet assay. The apoptotic features of hepatocytes
      were examined by immunohistochemistry and electron microscopic analyses. The
      hepatic triglyceride content markedly increased at wk 0 and wk +3 compared with
      the values at wk -3. The results of the comet assay showed increases in the mean
      tail moment values of hepatic cells after parturition in all cows, which
      suggested increased DNA damage. Histopathologically, the hepatocytes began to
      contain lipid droplets at wk 0 and were severely opacified at wk +3. Caspase-3
      positive and single-stranded DNA-(ssDNA)-positive cells were first detected in
      the liver after parturition. Condensation of nuclear chromatin, a typical sign of
      apoptosis, was confirmed by transmission electron microscopy after parturition.
      These results suggest that apoptosis is induced in hepatocytes of dairy cows
      around parturition and may result from lipotoxicity in hepatocytes.

PMID- 23543949
TI  - Toxin-associated and other genes in Clostridium perfringens type A isolates from
      bovine clostridial abomasitis (BCA) and jejunal hemorrhage syndrome (JHS).
AB  - This study examined known or possible virulence-associated genes in type A
      Clostridium perfringens from cases of both bovine clostridial abomasitis (BCA)
      and jejunal hemorrhage syndrome (JHS) and compared these to isolates from calves
      that were healthy or had undifferentiated diarrheal illness. A real-time
      polymerase chain reaction (PCR) assay was used to genotype the 218 C. perfringens
      isolates. Isolates were sourced from healthy and diarrheic young and mature
      cattle (n = 191), from calves with confirmed or suspected BCA (n = 22), and from
      mature cattle with JHS (n = 5). Of 216 isolates (96%), 208 were positive for the
      cpa gene and 13% (29/218) were positive for atypical cpb2. Three of 8 (37.5%)
      confirmed BCA isolates, 2 of 13 (15.4%) suspected BCA isolates, and no JHS
      isolates tested positive for atypical cpb2. As all isolates were negative for
      cpb, cpb2, cpe, etx, netB, and tpeL, the results of the present study do not
      support a role for these genes in BCA or JHS. A subset of unique genes identified
      in 1 bovine clostridial abomasitis isolate (F262), for which a genome sequence is
      available, was searched for in 8 BCA isolates by PCR. None of the 10 genes was
      consistently present in all or even in a majority of BCA isolates. Many of these
      genes were also variably and inconsistently present in type A isolates from
      calves that did not have BCA. Although a virulence signature to aid in the
      diagnosis of BCA caused by C. perfringens type A was not identified, further work
      may discover a gene or group of genes that would constitute such a signature.

PMID- 23543950
TI  - Suppression of immune responses in pigs by nonstructural protein 1 of porcine
      reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is characterized by a
      delayed and defective adaptive immune response. The viral nonstructural protein 1
      (NSP1) of the PRRS virus (PRRSV) is able to suppress the type I interferon (IFN)
      response in vitro. In this study, recombinant adenoviruses (rAds) expressing NSP1
      (rAd-NSP1), glycoprotein 5 (GP5) (rAd-GP5), and the NSP1-GP5 fusion protein (rAd
      NSP1-GP5) were constructed, and the effect of NSP1 on immune responses was
      investigated in pigs. Pigs inoculated with rAd-NSP1 or rAd-NSP1-GP5 had
      significantly lower levels of IFN-gamma and higher levels of the
      immunosuppressive cytokine IL-10 than pigs inoculated with rAd-GP5, wild-type
      adenovirus, or cell culture medium alone. The antibody response to vaccination
      against classic swine fever virus (CSFV) was significantly decreased by
      inoculation of NSP1 7 d after CSFV vaccination in pigs. Thus, NSP1-mediated
      immune suppression may play an important role in PRRSV pathogenesis.

PMID- 23543951
TI  - Prior determination of baseline minimum alveolar concentration (MAC) of
      isoflurane does not influence the effect of ketamine on MAC in rabbits.
AB  - The objective of this study was to compare the effect on the minimum alveolar
      concentration (MAC) of isoflurane when ketamine was administered either after or
      without prior determination of the baseline MAC of isoflurane in rabbits. Using a
      prospective randomized crossover study, 8 adult, female New Zealand rabbits were
      allocated to 2 treatment groups. Anesthesia was induced and maintained with
      isoflurane. Group 1 (same-day determination) had the MAC-sparing effect of
      ketamine [1 mg/kg bodyweight (BW) bolus followed by a constant rate infusion
      (CRI) of 40 MUg/kg BW per min, given by intravenous (IV)], which was determined
      after the baseline MAC of isoflurane was determined beforehand. A third MAC
      determination was started 30 min after stopping the CRI. Group 2 (separate-day
      determination) had the MAC-sparing effect of ketamine determined without previous
      determination of the baseline MAC of isoflurane. A second MAC determination was
      started 30 min after stopping the CRI. In group 1, the MAC of isoflurane (2.15 +/
      0.09%) was significantly decreased by ketamine (1.63 +/- 0.07%). After stopping
      the CRI, the MAC was significantly less (2.04 +/- 0.11%) than the baseline MAC of
      isoflurane and significantly greater than the MAC during the CRI. In group 2,
      ketamine decreased isoflurane MAC (1.53 +/- 0.22%) and the MAC increased
      significantly (1.94 +/- 0.25%) after stopping the CRI. Minimum alveolar
      concentration (MAC) values did not differ significantly between the groups either
      during ketamine administration or after stopping ketamine. Under the study
      conditions, prior determination of the baseline isoflurane MAC did not alter the
      effect of ketamine on MAC. Both methods of determining MAC seemed to be valid for
      research purposes.

PMID- 23543952
TI  - Antimicrobial susceptibility and molecular subtypes of Staphylococcus aureus
      isolated from pig tonsils and cow's milk in China.
AB  - This study investigated and compared the antimicrobial resistance patterns and
      ribotypes of Staphylococcus aureus isolated from pig tonsils and cow's milk in
      China. A total of 90 isolates of S. aureus was included: 42 strains were isolated
      from tonsils of pigs and 48 from half-udder milk. The broth microdilution method
      and the double-disc diffusion test (D test) were used for antimicrobial
      susceptibility testing. The mecA gene for methicillin-resistant S. aureus (MRSA)
      and the ermA, ermB, ermC, and msrA genes for erythromycin-resistant strains were
      detected by polymerase chain reaction (PCR). The isolates were ribotyped with the
      Riboprinter system. The highest frequency of resistance was observed with
      clindamycin (91.1%), followed by penicillin (90.0%), and erythromycin (85.6%).
      All strains were susceptible to vancomycin and trimethoprim-sulfamethoxazole. The
      D test showed that 54.5% (42/77) of erythromycin-resistant isolates had the
      constitutive resistance phenotype and 45.5% (35/77) had the inducible resistance
      phenotype to clindamycin. A higher proportion of resistance to cephalosporins,
      macrolides, fluoroquinolones, and pleuromutilins was observed in pig isolates
      than in milk isolates (P < 0.05). The mecA gene was detected in all MRSA
      isolates; 89.6% of erythromycin-resistant strains harbored the ermC gene and
      16.9% harbored the ermB gene. A total of 35 different ribogroups was found among
      the isolates investigated; 83.3% of pig strains belonged to 1 cluster with a
      similarity coefficient of 0.84. In contrast, 3 main clusters were observed among
      68.8% of milk strains, which indicates a high degree of host specificity.

PMID- 23543953
TI  - Hypercapnic respiratory acidosis: a protective or harmful strategy for critically
      ill newborn foals?
AB  - This paper reviews both the beneficial and adverse effects of permissive
      hypercapnic respiratory acidosis in critically ill newborn foals. It has been
      shown that partial carbon dioxide pressure (PCO2) above the traditional safe
      range (hypercapnia), has beneficial effects on the physiology of the respiratory,
      cardiovascular, and nervous system in neonates. In human neonatal critical care
      medicine permissive hypercapnic acidosis is generally well-tolerated by patients
      and is more beneficial to their wellbeing than normal carbon dioxide (CO2)
      pressure or normocapnia. Even though adverse effects of hypercapnia have been
      reported, especially in patients with central nervous system pathology and/or
      chronic infection, critical care clinicians often artificially increase PCO2 to
      take advantage of its positive effects on compromised neonate tissues. This is
      referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is
      common in critically ill newborn foals and has traditionally been considered as
      not beneficial. A search of online scientific databases was conducted to survey
      the literature on the effects of hypercapnia in neonates, with emphasis on
      newborn foals. The dynamic status of safety levels of PCO2 and data on the
      effectiveness of different carbon dioxide levels are not available for newborn
      foals and should be scientifically determined. Presently, permissive hypercapnia
      should be implemented or tolerated cautiously in compromised newborn foals and
      its use should be based on relevant data from adult horses and other species.

PMID- 23543954
TI  - Effects of selenium source on measures of selenium status and immune function in
      horses.
AB  - The effects of selenium (Se) supplementation and source on equine immune function
      have not been extensively studied. This study examined the effects of oral Se
      supplementation and Se source on aspects of innate and adaptive immunity in
      horses. Fifteen horses were assigned to 1 of 3 groups (5 horses/group): control,
      inorganic Se (sodium selenite), organic Se (Se yeast). Immune function tests
      performed included: lymphocyte proliferation in response to mitogen concanavalin
      A, neutrophil phagocytosis, antibody production after rabies vaccination,
      relative cytokine gene expression in stimulated lymphocytes [interferon gamma
      (IFNgamma), interleukin (IL)-2, IL-5, IL-10, tumor necrosis factor alpha
      (TNFalpha)], and neutrophils (IL-1, IL-6, IL-8, IL-12, TNFalpha). Plasma, red
      blood cell Se, and blood glutathione peroxidase activity were measured. Plasma
      and red blood cell Se were highest in horses in the organic Se group, compared
      with that of inorganic Se or control groups. Organic Se supplementation increased
      the relative lymphocyte expression of IL-5, compared with inorganic Se or no Se.
      Selenium supplementation increased relative neutrophil expression of IL-1 and IL
      8. Other measures of immune function were unaffected. Dietary Se content and
      source appear to influence immune function in horses, including alterations in
      lymphocyte expression of IL-5, and neutrophil expression of IL-1 and IL-8.

PMID- 23543955
TI  - Serum IgG response in calves to the putative pneumonic virulence factor Gs60 of
      Mannheimia haemolytica A1.
AB  - Bovine pneumonic pasteurellosis vaccines incorporate various antigens of
      Mannheimia haemolytica, including the acknowledged virulence factor leukotoxin
      (Lkt), and Gs60, a surface lipoprotein. To examine the role of antibodies to Gs60
      in protection, an enzyme-linked immunosorbent assay (ELISA) was developed for
      retrospective analysis of serum samples from previous trials in which vaccines
      containing native or recombinant Gs60 were administered parenterally. The
      analysis revealed a positive correlation between the titer of antibodies to Gs60
      and protection against experimental challenge in both vaccinates and naturally
      exposed controls. There was a strong correlation between production of IgG
      antibodies to Gs60 and Lkt neutralizing antibodies. Analysis of the relationship
      between the serum antibody titers and resistance to experimental challenge using
      linear statistical models revealed a significant association between prechallenge
      titers of serum antibodies to Lkt and protection. Further analysis suggested that
      antibodies against Gs60 were beneficial when Lkt neutralizing antibody titers
      were low.

PMID- 23543956
TI  - Efficacy of parenteral vaccination against porcine circovirus type 2 (PCV2) in
      seropositive piglets.
AB  - This study investigated if parenteral administration of a prototype adjuvanted
      vaccine against porcine circovirus type 2 (PCV2) could override maternally
      derived antibodies and induce acquired immunity in young piglets. Piglets with
      high levels of maternal PCV2 antibodies at 1 wk of age were randomly grouped into
      vaccinates and controls on the basis of body weight and inoculated with the
      vaccine or a control preparation twice, with an interval of 3 wk. Both groups
      were challenged 3 wk after the booster vaccination and euthanized 3 wk after
      challenge. The pigs were evaluated for clinical disease, histologic lesions in
      sections of gastric and left inguinal lymph nodes stained with hematoxylin and
      eosin, and the amount of PCV2 antigen in the lymph nodes by immunohistochemical
      study. The PCV2 antibody titers were monitored by competitive enzyme-linked
      immunosorbent assay throughout the experiment. The vaccinates showed
      significantly less decline (P < 0.05) in PCV2 antibody titers after the booster
      vaccination. Clinical disease did not develop in any of the piglets. The
      vaccinates and controls did not differ in either histologic lesions or amount of
      PCV2 antigen in the lymph nodes. This study demonstrated some evidence of priming
      of young piglets in the presence of maternal antibodies. Further studies are
      recommended to determine the optimum concentration of PCV2 antigen and a suitable
      adjuvant for the vaccine to achieve the full potential of the strategy of
      inducing acquired immunity in young piglets that have maternally derived
      antibodies.

PMID- 23543957
TI  - Effects of 2 different infusion rates of medetomidine on sedation score,
      cardiopulmonary parameters, and serum levels of medetomidine in healthy dogs.
AB  - The effects of 2 different continuous rate infusions (CRIs) of medetomidine over
      an 8-hour period on sedation score, selected cardiopulmonary parameters, and
      serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a
      crossover study design. The treatment groups were: CONTROL = saline bolus
      followed by saline CRI; MED1 = 2 MUg/kg body weight (BW) medetomidine loading
      dose followed by 1 MUg/kg BW per hour CRI; and MED2 = 4 MUg/kg BW medetomidine
      loading dose followed by 2 MUg/kg BW per hour CRI. Sedation score (SS), heart
      rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure
      (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP),
      arterial and mixed venous blood gas analyses, lactate, and plasma levels of
      medetomidine were evaluated at baseline, at various intervals during the
      infusion, and 2 h after terminating the infusion. Statistical analysis involved a
      repeated measures linear model. Both infusion rates of medetomidine-induced dose
      dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP
      were measured. Respiratory rate (RR), TEMP, central venous pH, central venous
      oxygen tension, and oxygen extraction ratio also decreased significantly in the
      MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions
      were not significantly affected by either infusion rate. In healthy dogs, both
      infusion rates of medetomidine-induced clinically relevant sedative effects,
      accompanied by typical alpha2 agonist-induced hemodynamic effects, which
      plateaued during the infusion and subsequently returned to baseline. While
      additional studies in unhealthy animals are required, the results presented here
      suggest that medetomidine infusions at the doses studied may be useful in canine
      patients requiring sedation for extended periods.

PMID- 23543958
TI  - Effects of body weight on antibody titers against canine parvovirus type 2,
      canine distemper virus, and canine adenovirus type 1 in vaccinated domestic adult
      dogs.
AB  - The objective of this study was to determine whether post-vaccination antibody
      titers vary according to body weight in adult dogs. Antibody titers against
      canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine
      adenovirus type 1 (CAdV-1) were measured for 978 domestic adult dogs from 2 to 6
      y of age. The dogs had been vaccinated approximately 12 mo earlier with a
      commercial combination vaccine. The dogs were divided into groups according to
      their weight. It was found that mean antibody titers in all weight groups were
      sufficient to prevent infection. Intergroup comparison, however, revealed that
      CPV-2 antibody titers were significantly higher in the Super Light (< 5 kg) group
      than in the Medium (10 to 19.9 kg) and Heavy (> 20 kg) groups and were also
      significantly higher in the Light (5 to 9.9 kg) group than in the Heavy group.
      Antibody titers against CDV were significantly higher in the Super Light, Light,
      and Medium groups than in the Heavy group. There were no significant differences
      among the groups for the CAdV-1 antibody titers.

PMID- 23543959
TI  - Do You See What I See? School Perspectives of Deaf Children, Hearing Children,
      and Their Parents.
AB  - Perspectives on academic and social aspects of children's school experiences were
      obtained from deaf and hearing children and their (deaf or hearing) parents.
      Possible differences between (1) the views of children and their parents and (2)
      those of hearing children and their parents compared to deaf children and their
      parents were of particular interest. Overall, parents gave their children higher
      school friendship ratings than the children gave themselves, and hearing children
      and their parents were more positive about children's friendships than were deaf
      children and their parents. Both children and parents also saw deaf children as
      less successful in reading than hearing children. However, deaf children's having
      deaf parents, attending a school for the deaf, and using sign language at home
      all were associated with more positive perceptions of social success. Use of
      cochlear implants was not associated with perceptions of greater academic or
      social success. These and related findings are discussed in the context of parent
      and child perspectives on social and academic functioning and particular
      challenges confronted by deaf children in regular school settings.

PMID- 23543960
TI  - Model for the cost-efficient delivery of continuous quality cancer care: a
      hospital and private-practice collaboration.
AB  - Cancer care is expensive due to the high costs of treatment and preventable
      utilization of resources. Government, employer groups, and insurers are seeking
      cancer care delivery models that promote both cost-efficiency and quality care.
      Baylor University Medical Center at Dallas (BUMC), a large tertiary care
      hospital, in collaboration with Texas Oncology, a large private oncology
      practice, established two independent centers that function cooperatively within
      the Baylor Charles A. Sammons Cancer Center, the Oncology Evaluation and
      Treatment Center (OETC) and Infusion Center, to deliver urgent care and infusions
      after hours to oncology patients. Quality measures based on evidence-based care
      and cost-efficiency measures were implemented within these centers. Ability to
      meet predetermined goals for these measures will be a guide for implementing
      continuous quality and cost-efficiency interventions. During the first two
      quarters of operations, 2023 patients received care in the OETC (n = 423) and
      Infusion Center (n = 1600). The average time spent in the OETC was 48% less than
      the time spent in the BUMC emergency department (ED). Eighty-nine percent of the
      cancer center' patients who received urgent care at BUMC were referred to the
      OETC for this care, instead of the BUMC ED. The hospital admission rate in the
      OETC was 59% lower than it was in the BUMC ED, a high-volume level I trauma
      center. The addition of the OETC and Infusion Center to the cancer center holds
      promise for providing continuous quality cancer care that is cost-efficient.

PMID- 23543962
TI  - Impact of sham-controlled vertebroplasty trials on referral patterns at two
      academic medical centers.
AB  - Debate persists regarding the merit of vertebroplasty following publication of
      blinded vertebroplasty trials in 2009, one of which was the Investigational
      Vertebroplasty Efficacy and Safety Trial (INVEST). This study was performed to
      determine whether referring physicians at two academic medical centers were aware
      of the trial results and to assess if this awareness prompted a change in their
      treatment of osteoporotic fractures. E-mail surveys were distributed to
      physicians within the Mayo Clinic and Baylor Health Care System (BHCS). Of 1390
      surveys sent, 194 (14%) were returned. Results showed that 92 of 158 respondents
      (58%) reported familiarity with INVEST; 66 of 92 (72%) agreed that INVEST changed
      their understanding of vertebroplasty efficacy; and 64 of 92 (70%) agreed that
      INVEST diminished their enthusiasm to refer patients for vertebroplasty. However,
      105 of 159 respondents (66%) felt vertebroplasty was an effective procedure in
      appropriate patients. Mayo physicians were more likely than BHCS physicians to be
      aware of INVEST (73% vs 67%, P < .0001), respond that INVEST changed their
      understanding of the appropriate treatment for osteoporotic compression fractures
      (79% vs 57%, P = 0.026), view vertebroplasty less favorably (45% vs 21%, P =
      0.005), and treat osteoporotic compression fractures with medical therapy/pain
      management alone (73% vs 48%, P = 0.003). INVEST changed referring physicians'
      understanding of the role of vertebroplasty and diminished their willingness to
      refer osteoporotic compression fracture patients; the impact varied by location.

PMID- 23543961
TI  - Thermoregulatory catheter-associated inferior vena cava thrombus.
AB  - The use of thermoregulatory catheters (TRCs) in critically ill patients has
      become increasingly popular. TRCs have been shown to be effective in regulating
      patient body temperature with improved outcomes. Critically ill patients,
      especially multitrauma patients and those with femoral catheters, are at high
      risk for deep vein thrombosis (DVT). Among patients for whom chemical DVT
      prophylaxis is not an option, inferior vena cava (IVC) filters are often placed
      prophylactically. The development of intravascular ultrasound (IVUS) has allowed
      placement of IVC filters at the bedside for patients who are too ill for
      transport to the operating room or cardiac catheterization lab. After
      encountering several patients with occult DVT of the IVC during bedside IVC
      filter placement, we performed a retrospective review to determine the incidence
      of DVT or pulmonary embolus (PE) in patients who had been treated with a TRC at
      Baylor University Medical Center at Dallas. Since 2008, IVC filters have been
      deployed at the bedside with the use of IVUS at Baylor University Medical Center.
      During that same time period, 83 patients had a TRC placed for either
      intravascular warming or cooling during their resuscitation. Forty-seven out of
      83 patients who had a TRC placed survived their injuries. Ten of 47 patients
      (21%) were diagnosed with DVT or PE, and 6 of these 10 (60%) were found to have
      caval thrombus. We present this case series as evidence that undiagnosed IVC
      thrombus associated with TRCs may be higher than previously suspected, given that
      5 out of 10 patients who had IVUS of their IVC for prophylactic IVC filter
      placement, as well as one patient diagnosed with PE, were found to have caval
      thrombus.

PMID- 23543963
TI  - High-intensity, occupation-specific training in a series of firefighters during
      phase II cardiac rehabilitation.
AB  - Six male firefighters who were referred to phase II cardiac rehabilitation after
      coronary revascularization participated in a specialized regimen of high
      intensity, occupation-specific training (HIOST) that simulated firefighting
      tasks. During each session, the electrocardiogram, heart rate, and blood pressure
      were monitored, and the patients were observed for adverse symptoms. No patient
      had to discontinue HIOST because of adverse arrhythmias or symptoms. For
      physicians who must make decisions about return to work, the information
      collected over multiple HIOST sessions might be more thorough and conclusive than
      the information gained during a single treadmill exercise stress test (the
      recommended evaluation method).

PMID- 23543964
TI  - Morphological features of temporal arteritis.
AB  - Although it varies from center to center, the frequency of temporal artery biopsy
      in patients suspected of having temporal arteritis (TA) is relatively small. Most
      commonly, patients suspected of having TA are placed on prednisone for varying
      periods of time, and if symptoms disappear or lessen the diagnosis is made.
      During a recent 13-year period at Baylor University Medical Center at Dallas, 15
      patients with TA had the diagnosis of TA confirmed by histological examination of
      a biopsy of one temporal artery. The length of the biopsied artery varied from
      0.7 to 5.5 cm (mean 2.7). The 15 patients ranged in age from 68 to 94 years (mean
      82, median 85), and 11 (73%) were women. In 13 of the 15 patients (87%), the
      lumen of the temporal artery was narrowed >95% in cross-sectional area by the
      panarteritis, and the temporal artery was associated with giant cells in 11
      patients (73%). Large collections of erythrocytes were present in the inflamed
      arterial walls in 5 patients (33%). All 15 patients were treated with varying
      doses of prednisone with favorable response in each. Eight patients (53%) died
      from 1 to 105 months (mean 52, median 57) after biopsy of the temporal artery. We
      have neither positive nor negative evidence that the TA played a role in the
      patients' death. Despite the present study and numerous others in the last 70
      years, the cause of TA remains a mystery.

PMID- 23543965
TI  - Quality of life of HIV/AIDS patients in a secondary health care facility, Ilorin,
      Nigeria.
AB  - This study evaluated the quality of life (QoL) and associated factors for 160
      HIV/AIDS patients in Sobi Specialist Hospital, Ilorin, Nigeria. The patients were
      assessed with the World Health Organization Quality of Life Questionnaire-Short
      Version. Frequency distribution, percentages, and means were employed for the
      statistical analysis of the results. The mean age of the HIV/AIDS patients was
      38.0 years; 70% were females, 55% were literates, more than three quarters were
      married, and one third were businessmen/women. The overall mean scores for health
      related QoL were 72 for the physical domain, 67 for the psychological domain, 65
      for the environment domain, and 47 for the social domain. Significant differences
      were observed in all domains among patients who had received 12 months of
      antiretroviral therapy compared with those who had just begun therapy. Marital
      status, fewer pills, and longer duration of therapy appeared to predict better
      QoL in this study. The improved QoL in the physical, psychological, and
      environmental domains is suggestive of the interventions offered to the patients
      by the pharmacists in this setting.

PMID- 23543966
TI  - Timing and causes of death after injuries.
AB  - Currently, long-term outcomes are significant because health care system changes
      will likely lead to a single payment for each occurrence of care, including
      readmissions-the "bundled payment" system. Therefore, it is essential to
      understand the outcomes of trauma patients discharged alive from trauma centers.
      This article reviews the current knowledge base on the timing and causes of
      deaths after trauma. The trimodal mortality model (immediate deaths, early
      deaths, and late deaths) is utilized as the early research describing trimodal
      distribution is discussed. Also covered is the successive work as trauma systems
      matured, showing a shift toward a bimodal distribution with a decline in late
      deaths. Finally, studies of long-term outcomes are highlighted. Deaths occurring
      within minutes or a few hours of injury are largely unchanged, which underscores
      the enormity of injuries to the central nervous and cardiovascular systems. Late
      deaths caused by multiple organ failure and sepsis have declined considerably,
      however. Also, the causes of death in this patient population remain constant.
      Lastly, a considerable number of deaths after discharge may be due to
      nontraumatic causes.

PMID- 23543968
TI  - Our experience as a Health Volunteers Overseas-sponsored team in Hue', Vietnam.
AB  - A group from Texas Oncology and Baylor Charles A. Sammons Cancer Center traveled
      to Hue', Vietnam, as part of Health Volunteers Overseas. From February 21 to
      March 6, 2012, five Baylor Sammons medical oncologists and an oncology nurse
      worked with a medical oncologist and a surgeon at the Hue' College of Medicine
      and Pharmacy, suggesting approaches based on available resources. The two groups
      worked together to find optimal solutions for the patients. What stood out the
      most for the Baylor Sammons group was the Hue' team's remarkable work ethic,
      empathy for patients, and treatment resourcefulness. The Baylor Sammons group
      also identified several unmet needs that could potentially be addressed by future
      volunteers in Hue', including creation of an outpatient hospice program,
      establishment of breast cancer screening, modernization of the pathology
      department, instruction in and better utilization of pain management, better use
      of clinic space, and the teaching of oncology and English to medical students.
      There was a mutual exchange of knowledge between the two medical teams. The
      Baylor Sammons group not only taught but also learned how to take good care of
      patients with limited resources.

PMID- 23543969
TI  - A forgotten landmark medical study from 1932 by the Committee on the Cost of
      Medical Care.

PMID- 23543967
TI  - Facts and principles learned at the 39th Annual Williamsburg Conference on Heart
      Disease.

PMID- 23543970
TI  - The debate on national health insurance ... 80 years ago.

PMID- 23543971
TI  - Lymphoma in the breast.
AB  - Lymphoma is a rare neoplasm in the breast. In this location, it may be primary or
      secondary, depending on whether there is lymphoma elsewhere in the body. The most
      common presentation of breast lymphoma is a painless palpable mass,
      indistinguishable from that of breast carcinoma, although the treatment regimens
      for these two neoplasms differ vastly. Knowledge of the varied mammographic and
      sonographic presentations of breast lymphoma should prompt more frequent
      recognition of this unusual malignant entity. Proper diagnosis of this neoplasm
      is of the utmost importance to guide appropriate treatment planning and prevent
      unnecessary and potentially harmful surgery. We describe secondary breast
      lymphoma in a woman who had been diagnosed and treated for non-Hodgkin's lymphoma
      several years earlier.

PMID- 23543972
TI  - Inflammatory breast carcinoma.
AB  - Inflammatory breast carcinoma is a rare form of invasive breast cancer often
      characterized by erythema, warmth, and a classic "peau de orange" or "orange
      peel" appearance of the affected breast. The average age of onset is within the
      fourth and fifth decades. Lesions are usually detected and evaluated with
      mammography, sonography, and recently, breast magnetic resonance imaging. We
      present the case of a 49-year-old woman with inflammatory breast carcinoma in her
      left breast and describe the imaging appearance of this aggressive lesion on the
      modalities listed above. Because this lesion may be misdiagnosed as infection
      (i.e., mastitis) or as the sequelae of a dermatologic disorder, proper
      characterization of inflammatory breast carcinoma is of the utmost clinical and
      radiologic importance.

PMID- 23543973
TI  - Plasmablastic lymphoma following transplantation.
AB  - Posttransplant lymphoproliferative disorder is a serious complication following
      solid organ as well as hematopoietic stem cell transplantation due to prolonged
      immunosuppressive therapy. Plasmablastic lymphoma, although classically
      associated with HIV infection, has since been described in transplant patients as
      a variant of posttransplant lymphoproliferative disorder with varying clinical
      presentations. Here we add two additional cases to the literature: one following
      lung transplantation and one following pancreatic transplantation. In addition,
      the demographic, therapeutic, and immunophenotypic characteristics from prior
      reported cases are summarized.

PMID- 23543974
TI  - Recurrent acute inflammatory demyelinating polyradiculoneuropathy following R
      CHOP treatment for non-Hodgkin lymphoma.
AB  - Acute flaccid paralysis following chemotherapy has a wide differential diagnosis,
      including drug toxicity, acute inflammatory demyelinating polyradiculoneuropathy
      (AIDP), and malignant nerve infiltration. We present a case of recurrent acute
      quadriparesis due to AIDP following chemotherapy for non-Hodgkin lymphoma, which
      resolved each time following administration of intravenous immunoglobulin.
      Although many chemotherapeutic agents can cause neurologic side effects, such as
      peripheral neuropathy, drug toxicity as a cause is a diagnosis of exclusion.

PMID- 23543975
TI  - Endolymphatic sac tumor and otalgia.
AB  - Otalgia is a common complaint seen by general practitioners, but its etiology is
      vast. Rarely, otalgia could be secondary to a neoplasm. We describe a case of
      otalgia and ear discharge in which the imaging revealed a rare neoplasm, an
      endolymphatic sac tumor, which contributed to the patient's symptoms. The primary
      diagnosis was made via characteristic imaging features that were later confirmed
      by histology.

PMID- 23543976
TI  - Inguinal lymphadenopathy as the initial presentation of sarcoidosis.
AB  - Sarcoidosis is a multisystem disease of unknown etiology characterized by
      granuloma formation. Despite pulmonary involvement in most patients, sarcoidosis
      can have a varied presentation. Lymph node involvement is rarely found in
      isolation. Even rarer are cases of sarcoidosis presenting with peripheral edema.
      We describe a case of sarcoidosis presenting with isolated unilateral peripheral
      edema.

PMID- 23543977
TI  - Levamisole-induced vasculitis.
AB  - Levamisole-contaminated cocaine is an increasingly reported cause of a syndrome
      characterized by vasculitic skin lesions and immunologic abnormalities. With
      approximately 70% of cocaine in the United States now contaminated with
      levamisole, the incidence of this syndrome is likely to increase. We report two
      cases of this syndrome and review its clinical presentation, course, and
      prognosis.

PMID- 23543978
TI  - Kayser-Fleischer rings of acute Wilson's disease.
AB  - Here we describe a case of a 22-year-old woman who presented with acute liver
      failure and Kayser-Fleischer rings suggesting the diagnosis of Wilson's disease.

PMID- 23543979
TI  - Ascites with elevated protein content as the presenting sign of constrictive
      pericardial disease.
AB  - Two men, one 63 and one 52 years old, presented with ascites. Analysis of the
      ascitic fluid in both patients revealed a high protein content and an elevated
      serum-ascites gradient. Various studies showed the cause of the ascites to be
      constrictive pericardial disease. Total excision of their parietal pericardia
      relieved their symptoms, decreased their cardiac filling pressures, and increased
      their cardiac indices. These cases highlight the importance of suspecting
      pericardial constriction as an etiology for high-protein-count ascites.

PMID- 23543980
TI  - Congenitally bicuspid aortic valve in brothers: coarctation of the aorta with a
      normally functioning aortic valve in one and no coarctation but severe aortic
      stenosis in the other.
AB  - Described herein are two brothers, both with a congenitally bicuspid aortic valve
      one of which was stenotic and one of which functioned normally-and one with
      associated aortic isthmic coarctation. Summarized also are previously reported
      families with more than one member with a congenitally bicuspid aortic valve.

PMID- 23543981
TI  - A 21-year-old pregnant woman with congenital heart disease.

PMID- 23543982
TI  - Persistent giant U wave inversion with anoxic brain injury.
AB  - Various electrocardiographic changes have been reported in the setting of acute
      neurological events, among them large, upright U waves. In contrast, the
      occurrence of inverted U waves is strongly suggestive of cardiovascular disease,
      most commonly hypertension, coronary artery disease, or valvular abnormalities.
      Presented herein is the case of a 29-year-old man with previous anoxic brain
      injury (but without apparent cardiovascular disease) whose electrocardiogram
      demonstrated persistent giant inverted U waves.

PMID- 23543983
TI  - The calcium-alkali syndrome.
AB  - The milk-alkali syndrome was a common cause of hypercalcemia, metabolic
      alkalosis, and renal failure in the early 20th century. It was caused by the
      ingestion of large quantities of milk and absorbable alkali to treat peptic ulcer
      disease. The syndrome virtually vanished after introduction of histamine-2
      blockers and proton pump inhibitors. More recently, a similar condition called
      the calcium-alkali syndrome has emerged as a common cause of hypercalcemia and
      alkalosis. It is usually caused by the ingestion of large amounts of calcium
      carbonate salts to prevent or treat osteoporosis and dyspepsia. We describe a 78
      year-old woman who presented with weakness, malaise, and confusion. She was found
      to have hypercalcemia, acute renal failure, and metabolic alkalosis. Upon further
      questioning, she reported use of large amounts of calcium carbonate tablets to
      treat recent heartburn symptoms. Calcium supplements were discontinued, and she
      was treated with intravenous normal saline. After 5 days, the calcium and
      bicarbonate levels normalized and renal function returned to baseline. In this
      article, we review the pathogenesis of the calcium-alkali syndrome as well as the
      differences between the traditional and modern syndromes.

PMID- 23543984
TI  - Hepatitis C and recurrent treatment-resistant acute ischemic stroke.
AB  - Since the introduction of recombinant tissue plasminogen activator and
      thrombolysis, acute ischemic stroke has become a treatable disorder if the
      patient presents within the 4.5-hour time window. Typically, sporadic stroke is
      caused by atherosclerotic disease involving large or small cerebral arteries or
      secondary to a cardioembolic source often associated with atrial fibrillation. In
      the over-65-year age group, more rare causes of stroke, such as antiphospholipid
      syndromes, are unusual; such stroke etiologies are mostly seen in a younger age
      group (<55 years). Here we describe acute ischemic stroke in three patients >65
      years with hepatitis C-associated antiphospholipid antibodies. We suggest that
      screening for antiphospholipid disorders in the older patient might be warranted,
      with potential implications for therapeutic management and secondary stroke
      prevention.

PMID- 23543985
TI  - Diagnosis and management of delayed hemoperitoneum following therapeutic
      paracentesis.
AB  - Abdominal paracentesis is a frequently employed diagnostic and therapeutic
      procedure for patients with refractory ascites, typically in patients with
      cirrhosis. It is generally regarded as a safe procedure with significant
      complications occurring in <1% of cases. Most hemorrhagic complications are due
      to abdominal wall trauma, during which clear evidence of active bleeding is
      usually visualized during the procedure. Delayed hemoperitoneum is a rare
      complication of large-volume paracentesis in which clinical evidence of active
      bleeding is typically absent until substantial blood loss has taken place (often
      several days to a week later), leading to an exceedingly high mortality rate.
      Herein we describe a case of delayed hemoperitoneum in a 55-year-old man with
      heart failure. This case emphasizes the importance of identifying patients who
      are at high risk for delayed hemoperitoneum as well as the need to closely
      monitor complete blood counts in the days following a large-volume paracentesis.

PMID- 23543986
TI  - Facts and ideas from anywhere.

PMID- 23543987
TI  - Myeloperoxidase: a new twist to an old tale.

PMID- 23543988
TI  - Identification of novel mutations in exon 14 of the f8 gene in malaysian patients
      with severe hemophilia a.

PMID- 23543989
TI  - Various Anticoagulants and Fluoride do not Affect HbA1C Level.

PMID- 23543990
TI  - Universal Screening for Gestational Diabetes Mellitus (GDM): Mandatory.

PMID- 23543991
TI  - Indian contribution to obstetric & gynecological.

PMID- 23543992
TI  - Huge peritoneal hydatidosis mimicking ovarian cyst.

PMID- 23543993
TI  - Live birth following resection of multiple submucous myomas: a unique case
      report.

PMID- 23543994
TI  - Successful pregnancy after chemotherapy for choriocarcinoma.

PMID- 23543995
TI  - Androgen insensitivity syndrome (testicular feminization).

PMID- 23543996
TI  - Adrenal mass with pregnancy.

PMID- 23543997
TI  - Acute Abdomen in a Young Girl with Factor XIII Deficiency Perianesthetic Issues.

PMID- 23543998
TI  - President's Message.

PMID- 23543999
TI  - Training in trauma care.

PMID- 23544000
TI  - Reexpansion pulmonary edema.

PMID- 23544001
TI  - Gossipyboma-a case report.

PMID- 23544002
TI  - Trocar site hernia- a case series.

PMID- 23544003
TI  - A schwannoma in the middle mediastinum originated from the phrenic nerve.

PMID- 23544005
TI  - Wisdom: What is it?

PMID- 23544004
TI  - Repopulation of ovarian cancer cells after chemotherapy.
AB  - The high mortality rate caused by ovarian cancer has not changed for the past
      thirty years. Although most patients diagnosed with this disease respond to
      cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci
      of cells almost always escape therapy, manage to survive, and acquire the
      capacity to repopulate the tumor. Repopulation of ovarian cancer cells that
      escape front-line chemotherapy, however, is a poorly understood phenomenon. Here
      I analyze cancer-initiating cells, transitory senescence, reverse ploidy, and
      cellular dormancy as putative players in ovarian cancer cell repopulation. Under
      standard of care, ovarian cancer patients do not receive treatment between
      primary cytotoxic therapy and clinical relapse; understanding the mechanisms
      driving cellular escape from chemotherapy should lead to the development of low
      toxicity, chronic treatment approaches that can be initiated right after primary
      therapy to interrupt cell repopulation and disease relapse by keeping it dormant
      and, therefore, subclinical.

PMID- 23544006
TI  - Case 1: Why does my eye keep turning in?

PMID- 23544007
TI  - Case 2: Green vaginal discharge in a 7-year-old girl.

PMID- 23544009
TI  - Considerations in the initial management of follicular lymphoma.

PMID- 23544010
TI  - A systems biology approach reveals that tissue tropism to West Nile virus is
      regulated by antiviral genes and innate immune cellular processes.
AB  - The actions of the RIG-I like receptor (RLR) and type I interferon (IFN)
      signaling pathways are essential for a protective innate immune response against
      the emerging flavivirus West Nile virus (WNV). In mice lacking RLR or IFN
      signaling pathways, WNV exhibits enhanced tissue tropism, indicating that
      specific host factors of innate immune defense restrict WNV infection and
      dissemination in peripheral tissues. However, the immune mechanisms by which the
      RLR and IFN pathways coordinate and function to impart restriction of WNV
      infection are not well defined. Using a systems biology approach, we defined the
      host innate immune response signature and actions that restrict WNV tissue
      tropism. Transcriptional profiling and pathway modeling to compare WNV-infected
      permissive (spleen) and nonpermissive (liver) tissues showed high enrichment for
      inflammatory responses, including pattern recognition receptors and IFN signaling
      pathways, that define restriction of WNV replication in the liver. Assessment of
      infected livers from Mavs(-/-) * Ifnar(-/-) mice revealed the loss of expression
      of several key components within the natural killer (NK) cell signaling pathway,
      including genes associated with NK cell activation, inflammatory cytokine
      production, and NK cell receptor signaling. In vivo analysis of hepatic immune
      cell infiltrates from WT mice demonstrated that WNV infection leads to an
      increase in NK cell numbers with enhanced proliferation, maturation, and effector
      action. In contrast, livers from Mavs(-/-) * Ifnar(-/-) infected mice displayed
      reduced immune cell infiltration, including a significant reduction in NK cell
      numbers. Analysis of cocultures of dendritic and NK cells revealed both cell
      intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate
      NK cell effector activity. Taken together, these observations reveal a complex
      innate immune signaling network, regulated by the RLR and IFN signaling pathways,
      that drives tissue-specific antiviral effector gene expression and innate immune
      cellular processes that control tissue tropism to WNV infection.

PMID- 23544011
TI  - Rational engineering of recombinant picornavirus capsids to produce safe,
      protective vaccine antigen.
AB  - Foot-and-mouth disease remains a major plague of livestock and outbreaks are
      often economically catastrophic. Current inactivated virus vaccines require
      expensive high containment facilities for their production and maintenance of a
      cold-chain for their activity. We have addressed both of these major drawbacks.
      Firstly we have developed methods to efficiently express recombinant empty
      capsids. Expression constructs aimed at lowering the levels and activity of the
      viral protease required for the cleavage of the capsid protein precursor were
      used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells
      at levels potentially attractive to industry using both vaccinia virus and
      baculovirus driven expression. Secondly we have enhanced capsid stability by
      incorporating a rationally designed mutation, and shown by X-ray crystallography
      that stabilised and wild-type empty capsids have essentially the same structure
      as intact virus. Cattle vaccinated with recombinant capsids showed sustained
      virus neutralisation titres and protection from challenge 34 weeks after
      immunization. This approach to vaccine antigen production has several potential
      advantages over current technologies by reducing production costs, eliminating
      the risk of infectivity and enhancing the temperature stability of the product.
      Similar strategies that will optimize host cell viability during expression of a
      foreign toxic gene and/or improve capsid stability could allow the production of
      safe vaccines for other pathogenic picornaviruses of humans and animals.

PMID- 23544012
TI  - Identification of a BRCA2-specific modifier locus at 6p24 related to breast
      cancer risk.
AB  - Common genetic variants contribute to the observed variation in breast cancer
      risk for BRCA2 mutation carriers; those known to date have all been found through
      population-based genome-wide association studies (GWAS). To comprehensively
      identify breast cancer risk modifying loci for BRCA2 mutation carriers, we
      conducted a deep replication of an ongoing GWAS discovery study. Using the ranked
      P-values of the breast cancer associations with the imputed genotype of 1.4 M
      SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina
      array that included a total of 211,155 SNPs as part of a multi-consortial
      project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2
      mutation carriers from 47 studies belonging to the Consortium of Investigators of
      Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated
      previously reported breast cancer susceptibility alleles in these BRCA2 mutation
      carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH)
      identified SNPs that have stronger evidence of association than those previously
      published. We also identified a novel susceptibility allele at 6p24 that was
      inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele
      HR = 0.85, 95% CI 0.80-0.90, P = 3.9 * 10(-8)). This SNP was not associated with
      breast cancer risk either in the general population or in BRCA1 mutation
      carriers. The locus lies within a region containing TFAP2A, which encodes a
      transcriptional activation protein that interacts with several tumor suppressor
      genes. This report identifies the first breast cancer risk locus specific to a
      BRCA2 mutation background. This comprehensive update of novel and previously
      reported breast cancer susceptibility loci contributes to the establishment of a
      panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This
      panel may have clinical utility for women with BRCA2 mutations weighing options
      for medical prevention of breast cancer.

PMID- 23544015
TI  - Can studies of pain help to bridge the gap between sensory and social impairments
      in autism?

PMID- 23544017
TI  - "The journey of a thousand miles...".

PMID- 23544014
TI  - Evidence of gene-environment interactions between common breast cancer
      susceptibility loci and established environmental risk factors.
AB  - Various common genetic susceptibility loci have been identified for breast
      cancer; however, it is unclear how they combine with lifestyle/environmental risk
      factors to influence risk. We undertook an international collaborative study to
      assess gene-environment interaction for risk of breast cancer. Data from 24
      studies of the Breast Cancer Association Consortium were pooled. Using up to
      34,793 invasive breast cancers and 41,099 controls, we examined whether the
      relative risks associated with 23 single nucleotide polymorphisms were modified
      by 10 established environmental risk factors (age at menarche, parity,
      breastfeeding, body mass index, height, oral contraceptive use, menopausal
      hormone therapy use, alcohol consumption, cigarette smoking, physical activity)
      in women of European ancestry. We used logistic regression models stratified by
      study and adjusted for age and performed likelihood ratio tests to assess gene
      environment interactions. All statistical tests were two-sided. We replicated
      previously reported potential interactions between LSP1-rs3817198 and parity
      (Pinteraction = 2.4 * 10(-6)) and between CASP8-rs17468277 and alcohol
      consumption (Pinteraction = 3.1 * 10(-4)). Overall, the per-allele odds ratio
      (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous
      women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26
      (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per
      allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and
      1.45 (1.14-1.85) in those who drank >= 20 g/day. Additionally, interaction was
      found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 * 10(
      5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92
      1.05) in nulliparous women. These data provide first strong evidence that the
      risk of breast cancer associated with some common genetic variants may vary with
      environmental risk factors.

PMID- 23544018
TI  - Conducting a winning literature search.
AB  - So what is a "winning literature search"? Simply put, it is one that provides you
      with the information you need to find the types of articles that will help you
      with clinical practice or research. Literature searching is a combination of an
      art and a science. Understanding the basic anatomy and physiology of searching
      can get you started on finding the information you need.

PMID- 23544016
TI  - Motor neglect and future directions for research.

PMID- 23544019
TI  - Heterotopic ossification in cervical disc arthroplasty: Is it clinically
      relevant?
AB  - STUDY DESIGN:  Retrospective cohort study. OBJECTIVE:  To analyze the presence
      and clinical relevance of heterotopic ossification (HO) at 3 years mean follow
      up. METHODS:  Thirty patients suffering from cervical radiculopathy and/or
      myelopathy treated with anterior disc replacement (ADR) were studied. HO was
      classified using the McAfee grading system. Range of motion was measured from
      flexion and extension x-rays. Short-form 36 and neck disability index (NDI)
      assessed functional outcome. RESULTS:  Forty-five prostheses were implanted in 30
      patients with cervical radiculopathy and/or myelopathy, mean age 40.9 years.
      Nineteen patients received 1 level and 11 patients received multilevel disc
      replacement. The incidence rate of HO was 42.2% (19 levels). Segmental range of
      motion was >=3 degrees  in 93.8% of patients with HO. There was no significant
      difference in functional scores between those who did and those who did not
      develop HO. Males tended to develop HO more frequently than females, though this
      was not statistically significant. The indication for surgery (soft disc hernia
      or spondylosis) was not associated with the formation of HO. CONCLUSIONS: 
      Functional improvement is maintained despite the presence of HO following
      cervical disc arthroplasty. Indications for arthroplasty should not be halted by
      the risk of HO. [Table: see text] The definiton of the different classes of
      evidence is available on page 83.

PMID- 23544013
TI  - Genome-wide association study in BRCA1 mutation carriers identifies novel loci
      associated with breast and ovarian cancer risk.
AB  - BRCA1-associated breast and ovarian cancer risks can be modified by common
      genetic variants. To identify further cancer risk-modifying loci, we performed a
      multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with
      breast and 1,839 were diagnosed with ovarian cancer), with a further replication
      in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast
      cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 * 10(
      8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian
      cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 * 10(-8), HR = 1.27, 95%
      CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 * 10(-8), HR = 1.20, 95% CI: 1.17
      1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the
      general population or BRCA2 carriers, suggesting a BRCA1-specific association.
      The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2
      carriers (P = 2*10(-4)). These loci may lead to an improved understanding of the
      etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint
      distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated
      that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk
      are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on
      the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest
      risk have an estimated lifetime risk of developing ovarian cancer of 28% or
      lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such
      differences in risk may have important implications for risk prediction and
      clinical management for BRCA1 carriers.

PMID- 23544020
TI  - Treating thoracic-disc herniations: Do we always have to go anteriorly?
AB  - STUDY DESIGN:  Retrospective cohort study. OBJECTIVE:  To determine if there is a
      difference in outcome and complications in surgically managed patients with
      thoracic-disc herniations (TDH) undergoing a modified transfacet pedicle-sparing
      decompression and fusion (posteriorly) compared to those undergoing anterior
      transthoracic discectomies (anteriorly). METHODS:  Thirty-five consecutive
      operatively managed TDH underwent operative management between March 2003 and
      November 2009. Outcomes and complications were reviewed from patient records and
      x-rays assessing differences between those treated posteriorly and those treated
      anteriorly. RESULTS:  Twenty-four patients underwent posterior management for 35
      TDH and ten patients underwent anterior management for twelve TDH. Mean age was
      50 years in both groups. Body mass index (BMI) averaged 28.8 in the anterior
      group and 32.0 in the posterior group. Follow-up averaged 38 weeks with four
      patients lost to follow-up (all posterior). Major complications secondary to
      surgery occurred in three patients (30%) in the anterior group (pulmonary
      embolus, pneumonia, and wrong level surgery) and in seven patients (35%) in the
      posterior group (seroma, misplaced instrumentation requiring revision, recurrence
      requiring an additional operation, and four infections). No neurological
      complications occurred and all patients noted improvement from baseline. Average
      length of stay was 7.3 days in the anterior group and 4.2 days in the posterior
      group (P < .003). Final pain as assessed by visual analog scale (VAS) improved
      from 6.7 to 4.3 in the anterior group and 6.9 to 2.3 in the posterior group (P =
      .05). CONCLUSIONS:  Complication rates are similar between groups and are
      approach related. Posteriorly managed patients had greater improvement in pain
      and shorter length of stay. [Table: see text] The definition of the different
      classes of evidence is available on page 83.

PMID- 23544021
TI  - Fueling the debate: Are outcomes better after posterior lumbar interbody fusion
      (PLIF) or after posterolateral fusion (PLF) in adult patients with low-grade
      adult isthmic spondylolisthesis?
AB  - STUDY DESIGN:  Retrospective cohort study. CLINICAL QUESTION:  Do more adult
      patients affected by low grade isthmic spondylolisthesis have significant
      clinical and radiological improvement following posterior lumbar interbody fusion
      (PLIF) than those who receive posterolateral fusion (PLF)? METHODS:  One hundred
      and fourteen patients affected by adult low grade isthmic spondylolisthesis,
      treated with posterior lumbar interbody fusion or posterolateral fusion, were
      reviewed. Clinical outcome was assessed by means of the questionnaires ODI, RMDQ
      and VAS. Radiographic evaluation included CT, MRI, and x-rays. The results were
      analyzed using the Student t-test. RESULTS:  The two groups were similar with
      respect to demographic and surgical characteristics. At an average follow-up of
      62.1 months, 71 patients were completely reviewed. Mean ODI, RMDQ and VAS scores
      didn't show statistically significant differences. Fusion rate was similar
      between the two groups (97% in PLIF group, 95% in PLF group). Major complications
      occurred in 5 of 71 patients reviewed (7%): one in the PLIF group (3.6%), four in
      the PLF group (9.3%). Pseudarthrosis occurred in one case in the PLIF group
      (3,6%) and in two cases in PLF group (4.6%). CONCLUSIONS:  In our series, there
      does not appear to be a clear advantage of posterior lumbar interbody fusion
      (PLIF) over posterolateral fusion (PLF) in terms of clinical and radiological
      outcome for treatment of adult low grade isthmic spondylolisthesis.

PMID- 23544022
TI  - The effect of body mass index on lumbar lordosis on the Mizuho OSI Jackson spinal
      table.
AB  - STUDY DESIGN:  Prospective cohort study. CLINICAL QUESTION:  Does the patients'
      body mass index (BMI) influence the degree of intraoperative lumbar lordosis in
      patients undergoing operative treatment on the Mizuho Orthopedic Systems
      Incorporated (OSI) Jackson spinal table? METHODS:  Twenty-four consecutive
      patients undergoing posterior spinal instrumentation and fusion on the Jackson
      table, excluding those with sagittal malalignment, underwent standing
      preoperative and prone intraoperative lateral x-rays. Intervertebral body angle
      measurements were obtained from L1-S1 using the modified method of Cobb. Changes
      in angle measurements were compared to BMI using linear regression and ANOVA.
      RESULTS:  We found a mean lordosis of 52.6 degrees  in standing preoperative x
      rays compared to a prone position mean lordosis of 61.5 degrees  on the Jackson
      table. The mean change was 8.88 degrees  with a range of 0 degrees -18 degrees .
      A linear association between lordosis and BMI was demonstrated (P < .0022). As
      BMI increased, so did lordosis (correlation coefficient, 0.59). CONCLUSIONS:  The
      current study is the first in which a correlation of patient body mass and use of
      the Jackson table has been evaluated. These data suggest that BMI influences
      lumbar lordosis on the Jackson table and that care must be used when dealing with
      a population with large BMI on the Jackson table. [Table: see text] The definiton
      of the different classes of evidence is available on page 83.

PMID- 23544023
TI  - Dynamic anterior cervical plating for multi-level spondylosis: Does it help?
AB  - STUDY DESIGN:  Randomized controlled trial. OBJECTIVE:  To compare fusion rates,
      time to fusion, complication rates and subsidence between 1) a static, 2) a
      dynamic angulation, and 3) a dynamic translation plate in anterior cervical
      discectomy and fusion for symptomatic degenerative cervical disease. METHODS: 
      Thirty-six patients with two level, symptomatic cervical degenerative changes
      requiring surgery were randomized in a blinded fashion to receive a statically
      locked plate, Cervical Spine Locking Plate (CSLP) (Synthes, Paoli, PN, USA), an
      Atlantis Vision((r)) Anterior Cervical Plate System (Medtronic, Memphis, TN, USA)
      which allows angular dynamization, or a Premier((r)) Anterior Cervical Plate
      System (Medtronic) which allows translational dynamization. Structured data
      collection and measurement protocols were used. Intervertebral composite
      allograft cages were used in all groups. Identical external immobilization and
      antiinflammatory medication protocols were followed. X-rays were obtained at
      preset time points postoperatively. Assessment of the primary outcomes was
      blinded. Rate of and time to fusion, graft/instrumentation complications,
      subsidence, and reoperation for adjacent level disease were measured. Paired t
      test and three-way Analysis of Variance test (ANOVA) were used to assess
      statistical differences between groups. RESULTS:  The three groups were similar
      demographically. Fusion rates in the CSLP, Atlantis and Premier plate groups were
      100%, 91%, and 92% respectively. Mean time to fusion was 6.1, 8.3 and 6.3 months
      respectively but differences were not statistically significant. Mean subsidence
      in the groups was 1.9, 1.6, and 2.6 mm respectively. Subsidence was found even
      for the static (CSLP) plate, but no statistically significant differences were
      found. CONCLUSIONS:  We found no clinical advantage of dynamic plates over static
      plates with regards to fusion rates, time to fusion, subsidence, complications,
      or adjacent-level surgery. Static plating allows for subsidence at similar levels
      to dynamic plating. [Table: see text] The definiton of the different classes of
      evidence is available on page 83.

PMID- 23544024
TI  - Kyphoplasty: Traditional imaging compared with computer-guided intervention-time
      to rethink technique?
AB  - STUDY DESIGN:  Equivalence trial (IRB not required for cadaveric studies).
      OBJECTIVE:  To compare computer-guided and fluoroscopic kyphoplasty. Factors of
      interest were radiation exposure, position of cannula within pedicles and
      procedure time. METHODS:  Kyphoplasty was performed on two cadavers. Computer
      navigated, cross-sectional images from a cone-beam CT were used for one and
      fluoroscopic imaging for the other. In each, T6-9 and T11-L2 vertebrae were
      selected. For both imaging methods, anteroposterior and lateral x-rays were
      taken. Radiation exposure for both procedures was measured by four dosimeters.
      Procedure time, radiation to surgeon and cadaver, and position of cannula
      placement within pedicles were recorded. The surgeon wore one under the lead
      gown, another on the lead gown at shoulder level, and a third as a ring on the
      dominant hand. A dosimeter was also placed on the cadaver. RESULTS:  The
      radiation from the cone-beam, computer-guided imaging system was 0.0 mrem to the
      surgeon and 0.52 rads to the cadaver. Using fluoroscopic imaging, surgeon's and
      cadaver's exposure was 5 mrem and 0.047 rads, respectively. Procedure times were
      similar and neither device resulted in cannula malposition. CONCLUSIONS:  Cone
      beam CT appears as accurate as the fluoroscopy; radiation exposure to the surgeon
      is eliminated, and radiation levels to the patient are acceptable.

PMID- 23544025
TI  - ProDisc-C versus fusion with Cervios chronOS prosthesis in cervical degenerative
      disc disease: Is there a difference at 12 months?
AB  - STUDY DESIGN:  Prospective cohort study. OBJECTIVE:  The aim of the study was to
      compare clinical results and to determine differences in outcomes between
      anterior cervical discectomy and fusion (ACDF) and disc arthroplasty in patients
      treated for symptomatic cervical degenerative disc disease. METHODS:  Forty
      patients with cervical degenerative disc disease were treated with ProDisc-C disc
      arthroplasty and 40 patients with fusion using an intervetebral spacer with
      integrated fixation (Cervios chronoOS) implants without additional anterior
      fixation. Fifty disc prostheses were placed in the first group and 52
      intervertebral spacers were implanted in the second group. Clinical outcomes were
      assessed before and 12 months following the procedure using the neck disability
      index (NDI) and visual analog scale (VAS) for neck and arm pain, with 15%
      improvement in NDI and 20% in VAS defined as a clinically significant. RESULTS: 
      Eighty patients with cervical degenerative disc disease with a mean age of 49.7
      years were included in the study with a minimum follow-up of 12 months. The
      groups were similar at baseline both clinically and statistically (P > .05)
      except for age and VAS for arm pain. Both groups had a statistically significant
      improvement in NDI and VAS for neck and arm pain (P < .05) and the arthroplasty
      group had a better improvement according to NDI (74.3% of patients in the
      arthroplasty group achieved >=15% improvement in NDI versus 65.7% of patients in
      ACDF group). CONCLUSIONS:  Both ProDisc C and Cervios chronoOS prostheses
      resulted in significant pain reduction and functional outcome for the patients
      with slightly better results in the group treated with disc arthroplasty 12
      months after the surgery. [Table: see text] The definiton of the different
      classes of evidence is available on page 83.

PMID- 23544026
TI  - Unilateral facet dislocations: Is surgery really the preferred option?
AB  - STUDY DESIGN:  Systematic review. OBJECTIVE:  To compare the safety and
      effectiveness of initial surgery versus nonoperative management of unilateral
      facet dislocations with or without fractures. SUMMARY OF BACKGROUND:  Unilateral
      facet injuries represent between 6%-10% of all cervical spine injuries and yet
      optimal treatment for these injuries has not been established. The surgeon is
      faced with the decision of whether to manage the injury operatively or
      nonoperatively. Providing evidence to support this decision is necessary and is
      the rationale behind this article. METHODS:  A systematic review of the English
      language literature was undertaken for articles published between 1970 and August
      2009. Electronic databases and reference lists of key articles were searched to
      identify studies evaluating surgery and nonoperative management of unilateral
      facet dislocations. Bilateral facet dislocations, isolated facet fractures
      (without dislocation), and complete spinal cord injuries were excluded. Two
      independent reviewers assessed the level of evidence quality using the GRADE
      criteria and disagreements were resolved by consensus. RESULTS:  We identified
      six articles meeting our inclusion criteria. Treatment failure, neurological
      deterioration, and persistent pain occurred more frequently in patients treated
      nonoperatively versus patients treated with surgery. Surgical patients
      experienced infections and surgical related complications not experience by those
      managed nonoperatively. Patients treated surgically after failed nonoperative
      management also experienced better outcomes than those who continued to be
      managed nonoperatively. CONCLUSION:  When faced with a patient requesting
      treatment recommendations for their acute unilateral facet dislocation, the
      surgeon can state that treatment failure, persistent pain, and neurological
      deterioration occur more frequently with nonoperative treatment based on the
      available literature. Ultimately it will be the preference of the patient that
      will decide between these two treatment approaches.

PMID- 23544027
TI  - Addressing the challenges and controversies of managing os odontoideum: results
      of a systematic review.
AB  - INTRODUCTION:  Os odontoideum is a rare condition with a controversial
      pathogenesis and poorly understood natural history. As a result, it is difficult
      for clinicians to predict which patients require surgical fusion to prevent
      symptomatic progression and potentially devastating neurologic injury. METHODS: 
      We undertook a systematic review of the literature to evaluate the clinical
      outcomes in the treatment of asymptomatic and symptomatic cases of os
      odontoideum. Pubmed, EMBASE, Cochrane, National Guideline Clearinghouse Databases
      as well as bibliographies of key articles were searched. Articles were reviewed
      by two independently working reviewers. Inclusion and exclusion criteria were set
      and each article was subject to a predefined quality rating scheme. RESULTS:  We
      identified eleven articles meeting our inclusion criteria. Seven studies included
      patients with asymptomatic os odontoideum discovered incidentally from which it
      was possible to examine data on 18 individuals. Six studies were identified
      containing more than 15 patients with symptomatic os odontoideum. CONCLUSION: 
      The existing literature regarding both asymptomatic or symptomatic os odontoideum
      and its treatment is very limited. No definitive conclusions can be drawn from
      these studies. A basic approach to the management of os odontoideum is offered
      based on the findings of this study.

PMID- 23544028
TI  - Metachronous presentation of metastasis from renal cell carcinoma: evaluation and
      management of spinal metastasis.

PMID- 23544029
TI  - Transgenic models of cardiac arrhythmias and sudden death.

PMID- 23544030
TI  - Transcranial direct current stimulation: challenges, opportunities, and impact on
      psychiatry and neurorehabilitation.

PMID- 23544031
TI  - Scientific scholarship and impact factors.

PMID- 23544032
TI  - Editorial: Mechanisms regulating immunity in plants.

PMID- 23544033
TI  - How fMRI Can Inform Cognitive Theories.
AB  - How can functional magnetic resonance imaging (fMRI) advance cognitive theory?
      Some have argued that fMRI can do little beyond localizing brain regions that
      carry out certain cognitive functions (and may not even be able to do that).
      However, in this article, we argue that fMRI can inform theories of cognition by
      helping to answer at least four distinct kinds of questions. Which mental
      functions are performed in brain regions specialized for just that function (and
      which are performed in more general-purpose brain machinery)? When fMRI markers
      of a particular Mental Process X are found, is Mental Process X engaged when
      people perform Task Y? How distinct are the representations of different stimulus
      classes? Do specific pairs of tasks engage common or distinct processing
      mechanisms? Thus, fMRI data can be used to address theoretical debates that have
      nothing to do with where in the brain a particular process is carried out. 

PMID- 23544034
TI  - The ripple effect: systems-level interventions to ameliorate pediatric pain.
AB  - The focus of this brief review is to highlight to the reader some of the 'ripple
      effects' of broader systems-level healthcare issues and the implications they may
      have for effective treatment of pediatric chronic pain. Many healthcare providers
      focus almost exclusively on the patient, but lack the knowledge of how to
      intervene effectively at systems levels with families, schools and healthcare
      institutions surrounding the pediatric patient with pain. We provide a case
      example and consider this issue across three systems that are particularly
      relevant to pediatric pain management: the outpatient pain clinic, school and
      inpatient settings. The information presented will improve the healthcare
      provider's ability to effectively treat pediatric pain through an enhanced
      understanding of the multiple systems of care that surround children with pain.

PMID- 23544035
TI  - Cyclothymic disorder in youth: why is it overlooked, what do we know and where is
      the field headed?
AB  - Cyclothymic disorder is a chronic and impairing subtype of bipolar disorder,
      largely neglected in pediatric research. Consequently, it is rarely diagnosed
      clinically despite potentially being the most prevalent form of bipolar disorder.
      Lack of attention has added to confusion about the diagnosis and clinical
      presentation of cyclothymic disorder. In pediatric studies, cyclothymic disorder
      is commonly grouped with 'subthreshold' presentations of bipolar disorder under
      the undifferentiated label 'bipolar disorder not otherwise specified'. However,
      research indicates that cyclothymic disorder can be reliably distinguished from
      the other forms of bipolar disorder and from other childhood disorders.
      Importantly, cyclothymic disorder may be a diathesis for more acute presentations
      of bipolar disorder, warranting a prominent role in dimensional models of mood
      and psychopathology. Current evidence suggests that cyclothymic disorder has the
      potential to make unique contributions to our understanding of the risk factors
      and outcomes associated with bipolar disorder. This potential has yet to be fully
      realized, limiting our knowledge and ability to intervene in a meaningful way
      with youth who are exhibiting symptoms of a major mood disorder. Including
      cyclothymic disorder in future research studies of children - particularly
      longitudinal outcome studies - is essential for understanding the developmental
      trajectory of bipolar spectrum disorders and learning how to accurately diagnosis
      and treat the full spectrum of bipolar disorders.

PMID- 23544036
TI  - Comparison of NIMS and MALDI platforms for neuropeptide and lipid mass
      spectrometric imaging in C. borealis brain tissue.
AB  - Nanostructure-initiator mass spectrometry (NIMS) is a recently developed matrix
      free laser desorption/ionization technique that has shown promise for peptide
      analyses. It is also useful in mass spectrometric imaging (MSI) studies of small
      molecule drugs, metabolites, and lipids, minimizing analyte diffusion caused by
      matrix application. In this study, NIMS and matrix-assisted laser
      desorption/ionization (MALDI) MSI of a crustacean model organism Cancer borealis
      brain were compared. MALDI was found to perform better than NIMS in these
      neuropeptide imaging experiments. Twelve neuropeptides were identified in MALDI
      MSI experiments whereas none were identified in NIMS MSI experiments. In
      addition, lipid profiles were compared using each ionization method. Both
      techniques provided similar lipid profiles in the m/z range 700 - 900.

PMID- 23544037
TI  - From brain states to mental phenomena via phase space transitions and
      renormalization group transformation: proposal of a theory.

PMID- 23544038
TI  - Reducing neonatal mortality in India: critical role of access to emergency
      obstetric care.
AB  - BACKGROUND: Neonatal mortality currently accounts for 41% of all global deaths
      among children below five years. Despite recording a 33% decline in neonatal
      deaths between 2000 and 2009, about 900,000 neonates died in India in 2009. The
      decline in neonatal mortality is slower than in the post-neonatal period, and
      neonatal mortality rates have increased as a proportion of under-five mortality
      rates. Neonatal mortality rates are higher among rural dwellers of India, who
      make up at least two-thirds of India's population. Identifying the factors
      influencing neonatal mortality will significantly improve child survival outcomes
      in India. METHODS: Our analysis is based on household data from the nationally
      representative 2008 Indian District Level Household Survey (DLHS-3). We use
      probit regression techniques to analyse the links between neonatal mortality at
      the household level and households' access to health facilities. The probability
      of the child dying in the first month of birth is our dependent variable.
      RESULTS: We found that 80% of neonatal deaths occurred within the first week of
      birth, and that the probability of neonatal mortality is significantly lower when
      the child's village is closer to the district hospital (DH), suggesting the
      critical importance of specialist hospital care in the prevention of newborn
      deaths. Neonatal deaths were lower in regions where emergency obstetric care was
      available at the District Hospitals. We also found that parental schooling and
      household wealth status improved neonatal survival outcomes. CONCLUSIONS:
      Addressing the main causes of neonatal deaths in India--preterm deliveries,
      asphyxia, and sepsis--requires adequacy of specialised workforce and facilities
      for delivery and neonatal intensive care and easy access by mothers and neonates.
      The slow decline in neonatal death rates reflects a limited attention to factors
      which contribute to neonatal deaths. The suboptimal quality and coverage of
      Emergency Obstetric Care facilities in India require urgent attention.

PMID- 23544039
TI  - Characteristics of near-death experiences memories as compared to real and
      imagined events memories.
AB  - Since the dawn of time, Near-Death Experiences (NDEs) have intrigued and,
      nowadays, are still not fully explained. Since reports of NDEs are proposed to be
      imagined events, and since memories of imagined events have, on average, fewer
      phenomenological characteristics than real events memories, we here compared
      phenomenological characteristics of NDEs reports with memories of imagined and
      real events. We included three groups of coma survivors (8 patients with NDE as
      defined by the Greyson NDE scale, 6 patients without NDE but with memories of
      their coma, 7 patients without memories of their coma) and a group of 18 age
      matched healthy volunteers. Five types of memories were assessed using Memory
      Characteristics Questionnaire (MCQ--Johnson et al., 1988): target memories (NDE
      for NDE memory group, coma memory for coma memory group, and first childhood
      memory for no memory and control groups), old and recent real event memories and
      old and recent imagined event memories. Since NDEs are known to have high
      emotional content, participants were requested to choose the most emotionally
      salient memories for both real and imagined recent and old event memories.
      Results showed that, in NDE memories group, NDE memories have more
      characteristics than memories of imagined and real events (p<0.02). NDE memories
      contain more self-referential and emotional information and have better clarity
      than memories of coma (all ps<0.02). The present study showed that NDE memories
      contained more characteristics than real event memories and coma memories. Thus,
      this suggests that they cannot be considered as imagined event memories. On the
      contrary, their physiological origins could lead them to be really perceived
      although not lived in the reality. Further work is needed to better understand
      this phenomenon.

PMID- 23544040
TI  - Gene expression profile of the hippocampus of rats subjected to chronic
      immobilization stress.
AB  - OBJECTIVE: This study systematically investigated the effect of chronic stress on
      the hippocampus and its damage mechanism at the whole genome level. METHODS: The
      rat whole genome expression chips (Illumina) were used to detect gene expression
      differences in the hippocampus of rats subjected to chronic immobilization stress
      (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene
      expression profile was studied through gene ontology and signal pathway analyses
      using bioinformatics. A differentially expressed transcription regulation network
      was also established. Real-time quantitative polymerase chain reaction (RT-PCR)
      was used to verify the microarray results and determine expression of the Gabra1,
      Fadd, Crhr2, and Cdk6 genes in the hippocampal tissues. RESULTS: Compared to the
      control group, 602 differentially expressed genes were detected in the
      hippocampus of rats subjected to stress for 7 days, while 566 differentially
      expressed genes were expressed in the animals experiencing stress for 21 days.
      The stress significantly inhibited the primary immune system functions of the
      hippocampus in animals subjected to stress for both 7 and 21 days. Immobilization
      activated the extracellular matrix receptor interaction pathway after 7 day
      exposure to stress and the cytokine-cytokine receptor interaction pathway. The
      enhanced collagen synthesis capacity of the hippocampal tissue was the core
      molecular event of the stress regulation network in the 7-day group, while the
      inhibition of hippocampal cell growth was the core molecular event in the 21-day
      group. For the Gabra1, Fadd, Crhr2, and Cdk6 genes, RT-PCR results were nearly in
      line with gene chip assay results. CONCLUSION: During the 7-day and 21-day stress
      processes, the combined action of polygenic, multilevel, and multi-signal
      pathways leads to the disorder of the immunologic functions of the hippocampus,
      hippocampal apoptosis, and proliferation disequilibrium.

PMID- 23544041
TI  - Markers of disease severity are associated with malnutrition in Parkinson's
      disease.
AB  - OBJECTIVE: In Parkinson's disease (PD), commonly reported risk factors for
      malnutrition in other populations commonly occur. Few studies have explored which
      of these factors are of particular importance in malnutrition in PD. The aim was
      to identify the determinants of nutritional status in people with Parkinson's
      disease (PWP). METHODS: Community-dwelling PWP (>18 years) were recruited (n =
      125; 73M/52F; Mdn 70 years). Self-report assessments included Beck's Depression
      Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI), Scales for Outcomes
      in Parkinson's disease-Autonomic (SCOPA-AUT), Modified Constipation Assessment
      Scale (MCAS) and Freezing of Gait Questionnaire (FOG-Q). Information about age,
      PD duration, medications, co-morbid conditions and living situation was obtained.
      Addenbrooke's Cognitive Examination (ACE-R), Unified Parkinson's Disease Rating
      Scale (UPDRS) II and UPDRS III were performed. Nutritional status was assessed
      using the Subjective Global Assessment (SGA) as part of the scored Patient
      Generated Subjective Global Assessment (PG-SGA). RESULTS: Nineteen (15%) were
      malnourished (SGA-B). Median PG-SGA score was 3. More of the malnourished were
      elderly (84% vs. 71%) and had more severe disease (H&Y: 21% vs. 5%). UPDRS II and
      UPDRS III scores and levodopa equivalent daily dose (LEDD)/body weight (mg/kg)
      were significantly higher in the malnourished (Mdn 18 vs. 15; 20 vs. 15; 10.1 vs.
      7.6 respectively). Regression analyses revealed older age at diagnosis, higher
      LEDD/body weight (mg/kg), greater UPDRS III score, lower STAI score and higher
      BDI score as significant predictors of malnutrition (SGA-B). Living alone and
      higher BDI and UPDRS III scores were significant predictors of a higher log
      adjusted PG-SGA score. CONCLUSIONS: In this sample of PWP, the rate of
      malnutrition was higher than that previously reported in the general community.
      Nutrition screening should occur regularly in those with more severe disease and
      depression. Community support should be provided to PWP living alone.
      Dopaminergic medication should be reviewed with body weight changes.

PMID- 23544042
TI  - Urban scaling and the production function for cities.
AB  - The factors that account for the differences in the economic productivity of
      urban areas have remained difficult to measure and identify unambiguously. Here
      we show that a microscopic derivation of urban scaling relations for economic
      quantities vs. population, obtained from the consideration of social and
      infrastructural properties common to all cities, implies an effective model of
      economic output in the form of a Cobb-Douglas type production function. As a
      result we derive a new expression for the Total Factor Productivity (TFP) of
      urban areas, which is the standard measure of economic productivity per unit of
      aggregate production factors (labor and capital). Using these results we
      empirically demonstrate that there is a systematic dependence of urban
      productivity on city population size, resulting from the mismatch between the
      size dependence of wages and labor, so that in contemporary US cities
      productivity increases by about 11% with each doubling of their population.
      Moreover, deviations from the average scale dependence of economic output,
      capturing the effect of local factors, including history and other local
      contingencies, also manifest surprising regularities. Although, productivity is
      maximized by the combination of high wages and low labor input, high productivity
      cities show invariably high wages and high levels of employment relative to their
      size expectation. Conversely, low productivity cities show both low wages and
      employment. These results shed new light on the microscopic processes that
      underlie urban economic productivity, explain the emergence of effective
      aggregate urban economic output models in terms of labor and capital inputs and
      may inform the development of economic theory related to growth.

PMID- 23544043
TI  - Prevalence and associations of incomplete posterior vitreous detachment in adult
      Chinese: the Beijing Eye Study.
AB  - PURPOSE: To determine prevalence and associations of incomplete posterior
      vitreous detachment (PVD). METHODS: The population-based cross-sectional Beijing
      Eye Study 2011 included 3468 individuals with a mean age of 64.6+/-9.8 years
      (range: 50-93 years). A detailed ophthalmic examination was performed including
      spectral-domain optical coherence tomography (SD-OCT). Incomplete PVD was
      differentiated into type 1 (shallow PVD with circular perifoveal vitreous
      attachment), type 2 (PVD reaching fovea but not foveola), type 3 (shallow PVD
      with pinpoint vitreous attachment at the foveola), and type 4 (PVD completely
      detached from the macula, attached to the optic disc). RESULTS: An incomplete PVD
      was detected in 3948 eyes (prevalence: 60.5+/-0.6%; 95% Confidence Interval (CI):
      59.3%,61.7%) of 2198 subjects (67.1+/-0.8%;95%CI: 65.6%,68.7%). Type 1 PVD was
      seen in 3090 (78.3%) eyes, type 2 PVD in 504 (12.8%) eyes, type 3 PVD in 70
      (1.8%) eyes, and type 4 PVD in 284 (7.2%) eyes. Prevalence of incomplete PVD was
      associated with younger age (P<0.001;OR:0.91), male gender (P<0.001;OR:0.64),
      rural region of habitation (P<0.001;OR:0.49), larger corneal diameter (P =
      0.04;OR:0.91), better best corrected visual acuity (P = 0.02;OR:0.41), and
      hyperopic refractive error (P<0.001;OR:1.15). The type of incomplete PVD was
      associated with higher age (P<0.001), urban region of habitation (P<0.001),
      myopic refractive error (P = 0.001), thinner cornea (P = 0.005), and better best
      corrected visual acuity (P = 0.056). CONCLUSIONS: In adult Chinese in Greater
      Beijing, prevalence of an incomplete PVD (detected in 67.1% subjects) was
      associated with younger age, male gender, rural region of habitation, larger
      corneal diameter, better best corrected visual acuity and hyperopic refractive
      error.

PMID- 23544044
TI  - The systemic cytokine environment is permanently altered in multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable bone marrow malignancy of the B cell
      lineage. Utilizing multiplex Luminex technology we measured levels of 25
      cytokines in the plasma of normal donors (n = 177), those with monoclonal
      gammopathy of undetermined significance (n = 8), and MM patients (n = 55) with
      either active disease, on treatment, or in remission. The cytokine levels were
      compared between normal donors and MM patients as well as between various phases
      of MM, and discriminant analysis was used to create a predictive classification
      model based on the differentially expressed cytokines. Evaluating age- and gender
      dependence of cytokine expression, we determined that with age there is a shift
      toward a pro-inflammatory environment. Moreover, we observed a strong gender bias
      in cytokine expression. However, the profile of differentially expressed
      cytokines was heavily skewed toward an anti-inflammatory, pro-tumorigenic
      response in patients with MM. Significantly, our predictive model placed all
      patients in remission in the same category as those with active disease. Thus,
      our study demonstrates that the homeostasis of systemic cytokines is not restored
      when MM patients enter remission, suggesting that once an individual has cancer,
      the microenvironment is permanently altered and the system is primed for a
      relapse.

PMID- 23544045
TI  - Genes related to ion-transport and energy production are upregulated in response
      to CO2-driven pH decrease in corals: new insights from transcriptome analysis.
AB  - Since the preindustrial era, the average surface ocean pH has declined by 0.1 pH
      units and is predicted to decline by an additional 0.3 units by the year 2100.
      Although subtle, this decreasing pH has profound effects on the seawater
      saturation state of carbonate minerals and is thus predicted to impact on
      calcifying organisms. Among these are the scleractinian corals, which are the
      main builders of tropical coral reefs. Several recent studies have evaluated the
      physiological impact of low pH, particularly in relation to coral growth and
      calcification. However, very few studies have focused on the impact of low pH at
      the global molecular level. In this context we investigated global transcriptomic
      modifications in a scleractinian coral (Pocillopora damicornis) exposed to pH 7.4
      compared to pH 8.1 during a 3-week period. The RNAseq approach shows that 16% of
      our transcriptome was affected by the treatment with 6% of upregulations and 10%
      of downregulations. A more detailed analysis suggests that the downregulations
      are less coordinated than the upregulations and allowed the identification of
      several biological functions of interest. In order to better understand the links
      between these functions and the pH, transcript abundance of 48 candidate genes
      was quantified by q-RT-PCR (corals exposed at pH 7.2 and 7.8 for 3 weeks). The
      combined results of these two approaches suggest that pH>=7.4 induces an
      upregulation of genes coding for proteins involved in calcium and carbonate
      transport, conversion of CO2 into HCO3(-) and organic matrix that may sustain
      calcification. Concomitantly, genes coding for heterotrophic and autotrophic
      related proteins are upregulated. This can reflect that low pH may increase the
      coral energy requirements, leading to an increase of energetic metabolism with
      the mobilization of energy reserves. In addition, the uncoordinated
      downregulations measured can reflect a general trade-off mechanism that may
      enable energy reallocation.

PMID- 23544046
TI  - Neural sensitivity to absolute and relative anticipated reward in adolescents.
AB  - Adolescence is associated with a dramatic increase in risky and impulsive
      behaviors that have been attributed to developmental differences in neural
      processing of rewards. In the present study, we sought to identify age
      differences in anticipation of absolute and relative rewards. To do so, we
      modified a commonly used monetary incentive delay (MID) task in order to examine
      brain activity to relative anticipated reward value (neural sensitivity to the
      value of a reward as a function of other available rewards). This design also
      made it possible to examine developmental differences in brain activation to
      absolute anticipated reward magnitude (the degree to which neural activity
      increases with increasing reward magnitude). While undergoing fMRI, 18
      adolescents and 18 adult participants were presented with cues associated with
      different reward magnitudes. After the cue, participants responded to a target to
      win money on that trial. Presentation of cues was blocked such that two reward
      cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus,
      the relative value of the $1.00 reward varied depending on whether it was paired
      with a smaller or larger reward. Reflecting age differences in neural responses
      to relative anticipated reward (i.e., reference dependent processing), adults,
      but not adolescents, demonstrated greater activity to a $1 reward when it was the
      larger of the two available rewards. Adults also demonstrated a more linear
      increase in ventral striatal activity as a function of increasing absolute reward
      magnitude compared to adolescents. Additionally, reduced ventral striatal
      sensitivity to absolute anticipated reward (i.e., the difference in activity to
      medium versus small rewards) correlated with higher levels of trait Impulsivity.
      Thus, ventral striatal activity in anticipation of absolute and relative rewards
      develops with age. Absolute reward processing is also linked to individual
      differences in Impulsivity.

PMID- 23544047
TI  - A statistical physics view of pitch fluctuations in the classical music from Bach
      to Chopin: evidence for scaling.
AB  - Because classical music has greatly affected our life and culture in its long
      history, it has attracted extensive attention from researchers to understand laws
      behind it. Based on statistical physics, here we use a different method to
      investigate classical music, namely, by analyzing cumulative distribution
      functions (CDFs) and autocorrelation functions of pitch fluctuations in
      compositions. We analyze 1,876 compositions of five representative classical
      music composers across 164 years from Bach, to Mozart, to Beethoven, to
      Mendelsohn, and to Chopin. We report that the biggest pitch fluctuations of a
      composer gradually increase as time evolves from Bach time to Mendelsohn/Chopin
      time. In particular, for the compositions of a composer, the positive and
      negative tails of a CDF of pitch fluctuations are distributed not only in power
      laws (with the scale-free property), but also in symmetry (namely, the
      probability of a treble following a bass and that of a bass following a treble
      are basically the same for each composer). The power-law exponent decreases as
      time elapses. Further, we also calculate the autocorrelation function of the
      pitch fluctuation. The autocorrelation function shows a power-law distribution
      for each composer. Especially, the power-law exponents vary with the composers,
      indicating their different levels of long-range correlation of notes. This work
      not only suggests a way to understand and develop music from a viewpoint of
      statistical physics, but also enriches the realm of traditional statistical
      physics by analyzing music.

PMID- 23544048
TI  - Curcumin inhibits transforming growth factor-beta1-induced EMT via PPARgamma
      pathway, not Smad pathway in renal tubular epithelial cells.
AB  - Tubulointerstitial fibrosis (TIF) is the final common pathway in the end-stage
      renal disease. Epithelial-to-mesenchymal transition (EMT) is considered a major
      contributor to the TIF by increasing the number of myofibroblasts. Curcumin, a
      polyphenolic compound derived from rhizomes of Curcuma, has been shown to possess
      potent anti-fibrotic properties but the mechanism remains elusive. We found that
      curcumin inhibited the EMT as assessed by reduced expression of alpha-SMA and PAI
      1, and increased E-cadherin in TGF-beta1 treated proximal tubular epithelial cell
      HK-2 cells. Both of the conventional TGF-beta1/Smad pathway and non-Smad pathway
      were investigated. Curcumin reduced TGF-beta receptor type I (TbetaR-I) and TGF
      beta receptor type II (TbetaR II), but had no effect on phosphorylation of Smad2
      and Smad3. On the other hand, in non-Smad pathway curcumin reduced TGF-beta1
      induced ERK phosphorylation and PPARgamma phosphorylation, and promoted nuclear
      translocation of PPARgamma. Further, the effect of curcumin on alpha-SMA, PAI-1,
      E-cadherin, TbetaR I and TbetaR II were reversed by ERK inhibitor U0126 or
      PPARgamma inhibitor BADGE, or PPARgamma shRNA. Blocking PPARgamma signaling
      pathway by inhibitor BADGE or shRNA had no effect on the phosphorylation of ERK
      whereas the suppression of ERK signaling pathway inhibited the phosphorylation of
      PPARgamma. We conclude that curcumin counteracted TGF-beta1-induced EMT in renal
      tubular epithelial cells via ERK-dependent and then PPARgamma-dependent pathway.

PMID- 23544049
TI  - Do male and female cowbirds see their world differently? Implications for sex
      differences in the sensory system of an avian brood parasite.
AB  - BACKGROUND: Male and female avian brood parasites are subject to different
      selection pressures: males compete for mates but do not provide parental care or
      territories and only females locate hosts to lay eggs. This sex difference may
      affect brain architecture in some avian brood parasites, but relatively little is
      known about their sensory systems and behaviors used to obtain sensory
      information. Our goal was to study the visual resolution and visual information
      gathering behavior (i.e., scanning) of brown-headed cowbirds.
      METHODOLOGY/PRINCIPAL FINDINGS: We measured the density of single cone
      photoreceptors, associated with chromatic vision, and double cone photoreceptors,
      associated with motion detection and achromatic vision. We also measured head
      movement rates, as indicators of visual information gathering behavior, when
      exposed to an object. We found that females had significantly lower density of
      single and double cones than males around the fovea and in the periphery of the
      retina. Additionally, females had significantly higher head-movement rates than
      males. CONCLUSIONS: Overall, we suggest that female cowbirds have lower chromatic
      and achromatic visual resolution than males (without sex differences in visual
      contrast perception). Females might compensate for the lower visual resolution by
      gazing alternatively with both foveae in quicker succession than males,
      increasing their head movement rates. However, other physiological factors may
      have influenced the behavioral differences observed. Our results bring up
      relevant questions about the sensory basis of sex differences in behavior. One
      possibility is that female and male cowbirds differentially allocate costly
      sensory resources, as a recent study found that females actually have greater
      auditory resolution than males.

PMID- 23544050
TI  - Mid-Neolithic exploitation of mollusks in the Guanzhong Basin of Northwestern
      China: preliminary results.
AB  - Mollusk remains are abundant in archaeological sites in the Guanzhong Basin of
      Northwestern China, providing good opportunities for investigations into the use
      of mollusks by prehistoric humans. Here we report on freshwater gastropod and
      bivalve mollusks covering the time interval from about 5600 to 4500 cal. yrs BP
      from sites of Mid-Late Neolithic age. They are identified as Cipangopaludina
      chinensis and Unio douglasiae, both of which are currently food for humans. The
      shells are well preserved and have no signs of abrasion. They are all freshwater
      gastropods and bivalves found in pits without water-reworked deposits and have
      modern representatives which can be observed in rivers, reservoirs, and paddy
      fields in the studied region. Mollusk shells were frequently recovered in
      association with mammal bones, lithic artifacts, and pottery. These lines of
      evidence indicate that the mollusks are the remains of prehistoric meals. The
      mollusk shells were likely discarded into the pits by prehistoric humans after
      the flesh was eaten. However, these mollusk remains may not have been staple food
      since they are not found in large quantities. Mollusk shell tools and ornaments
      are also observed. Shell tools include shell knives, shell reaphooks and
      arrowheads, whereas shell ornaments are composed of pendants and loops. All the
      shell tools and ornaments are made of bivalve mollusks and do not occur in large
      numbers. The finding of these freshwater mollusk remains supports the view that
      the middle Holocene climate in the Guanzhong Basin may have been warm and moist,
      which was probably favorable to freshwater mollusks growing and developing in the
      region.

PMID- 23544051
TI  - Stress within a restricted time window selectively affects the persistence of
      long-term memory.
AB  - The effects of stress on emotional memory are distinct and depend on the stages
      of memory. Memory undergoes consolidation and reconsolidation after acquisition
      and retrieval, respectively. Stress facilitates the consolidation but disrupts
      the reconsolidation of emotional memory. Previous research on the effects of
      stress on memory have focused on long-term memory (LTM) formation (tested 24 h
      later), but the effects of stress on the persistence of LTM (tested at least 1
      week later) are unclear. Recent findings indicated that the persistence of LTM
      requires late-phase protein synthesis in the dorsal hippocampus. The present
      study investigated the effect of stress (i.e., cold water stress) during the late
      phase after the acquisition and retrieval of contextual fear memory in rats. We
      found that stress and corticosterone administration during the late phase (12 h)
      after acquisition, referred to as late consolidation, selectively enhanced the
      persistence of LTM, whereas stress during the late phase (12 h) after retrieval,
      referred to as late reconsolidation, selectively disrupted the restabilized
      persistence of LTM. Moreover, the effects of stress on the persistence of LTM
      were blocked by the corticosterone synthesis inhibitor metyrapone, which was
      administered before stress, suggesting that the glucocorticoid system is involved
      in the effects of stress on the persistence of LTM. We conclude that stress
      within a restricted time window after acquisition or retrieval selectively
      affects the persistence of LTM and depends on the glucocorticoid system.

PMID- 23544052
TI  - Familial sinistrals avoid exact numbers.
AB  - We report data from an internet questionnaire of sixty number trivia.
      Participants were asked for the number of cups in their house, the number of
      cities they know and 58 other quantities. We compare the answers of familial
      sinistrals--individuals who are left-handed themselves or have a left-handed
      close blood-relative--with those of pure familial dextrals--right-handed
      individuals who reported only having right-handed close blood-relatives. We show
      that familial sinistrals use rounder numbers than pure familial dextrals in the
      survey responses. Round numbers in the decimal system are those that are
      multiples of powers of 10 or of half or a quarter of a power of 10. Roundness is
      a gradient concept, e.g. 100 is rounder than 50 or 200. We show that very round
      number like 100 and 1000 are used with 25% greater likelihood by familial
      sinistrals than by pure familial dextrals, while pure familial dextrals are more
      likely to use less round numbers such as 25, 60, and 200. We then use Sigurd's
      (1988, Language in Society) index of the roundness of a number and report that
      familial sinistrals' responses are significantly rounder on average than those of
      pure familial dextrals. To explain the difference, we propose that the cognitive
      effort of using exact numbers is greater for the familial sinistral group because
      their language and number systems tend to be more distributed over both
      hemispheres of the brain. Our data support the view that exact and approximate
      quantities are processed by two separate cognitive systems. Specifically, our
      behavioral data corroborates the view that the evolutionarily older, approximate
      number system is present in both hemispheres of the brain, while the exact number
      system tends to be localized in only one hemisphere.

PMID- 23544053
TI  - Evidence that mast cells are not required for healing of splinted cutaneous
      excisional wounds in mice.
AB  - Wound healing is a complex biological process involving the interaction of many
      cell types to replace lost or damaged tissue. Although the biology of wound
      healing has been extensively investigated, few studies have focused on the role
      of mast cells. In this study, we investigated the possible role of mast cells in
      wound healing by analyzing aspects of cutaneous excisional wound healing in three
      types of genetically mast cell-deficient mice. We found that C57BL/6-Kit(W-sh/W
      sh), WBB6F1-Kit(W/W-v), and Cpa3-Cre; Mcl-1(fl/fl) mice re-epithelialized
      splinted excisional skin wounds at rates very similar to those in the
      corresponding wild type or control mice. Furthermore, at the time of closure,
      scars were similar in the genetically mast cell-deficient mice and the
      corresponding wild type or control mice in both quantity of collagen deposition
      and maturity of collagen fibers, as evaluated by Masson's Trichrome and Picro
      Sirius red staining. These data indicate that mast cells do not play a
      significant non-redundant role in these features of the healing of splinted full
      thickness excisional cutaneous wounds in mice.

PMID- 23544054
TI  - Sperm cell population dynamics in ram semen during the cryopreservation process.
AB  - BACKGROUND: Sperm cryopreservation has become an indispensable tool in biology.
      Initially, studies were aimed towards the development of efficient freezing
      protocols in different species that would allow for an efficient storage of semen
      samples for long periods of time, ensuring its viability. Nowadays, it is widely
      known that an important individual component exists in the cryoresistance of
      semen, and efforts are aimed at identifying those sperm characteristics that may
      allow us to predict this cryoresistance. This knowledge would lead, ultimately,
      to the design of optimized freezing protocols for the sperm characteristics of
      each male. METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated the changes that
      occur in the sperm head dimensions throughout the cryopreservation process. We
      have found three different patterns of response, each of one related to a
      different sperm quality at thawing. We have been able to characterize males based
      on these patterns. For each male, its pattern remained constant among different
      ejaculates. This latter would imply that males always respond in the same way to
      freezing, giving even more importance to this sperm feature.
      CONCLUSIONS/SIGNIFICANCE: Changes in the sperm head during cryopreservation
      process have resulted useful to identify the ability of semen of males for
      freezing. We suggest that analyses of these response patterns would represent an
      important tool to characterize the cryoresistance of males when implemented
      within breeding programs. We also propose follow-up experiments to examine the
      outcomes of the use of different freezing protocols depending on the pattern of
      response of males.

PMID- 23544055
TI  - Sex determining region Y-box 2 (SOX2) amplification is an independent indicator
      of disease recurrence in sinonasal cancer.
AB  - OBJECTIVES: The transcription factor SOX2 (3q26.3-q27) is an embryonic stem cell
      factor contributing to the induction of pluripotency in terminally differentiated
      somatic cells. Recently, amplification of the SOX2 gene locus has been described
      in squamous cell carcinoma (SCC) of different organ sites. Aim of this study was
      to investigate amplification and expression status of SOX2 in sinonasal
      carcinomas and to correlate the results with clinico-pathological data. MATERIALS
      AND METHODS: A total of 119 primary tumor samples from the sinonasal region were
      assessed by fluorescence in-situ hybridization and immunohistochemistry for SOX2
      gene amplification and protein expression, respectively. Of these, 59 were SSCs,
      18 sinonasal undifferentiated carcinomas (SNUC), 10 carcinomas associated with an
      inverted papilloma (INVC), 19 adenocarcinomas (AD) and 13 adenoid cystic
      carcinomas (ACC). RESULTS: SOX2 amplifications were found in subsets of SCCs
      (37.5%), SNUCs (35.3%), INVCs (37.5%) and ADs (8.3%) but not in ACCs. SOX2
      amplification resulted in increased protein expression. Patients with SOX2
      amplified sinonasal carcinomas showed a significantly higher rate of tumor
      recurrences than SOX2 non-amplified tumors. CONCLUSION: This is the first study
      assessing SOX2 amplification and expression in a large cohort of sinonasal
      carcinomas. As opposed to AD and ACC, SOX2 amplifications were detected in more
      than 1/3 of all SCCs, SNUCs and INVCs. We therefore suggest that SNUCs are
      molecularly closely related to SCCs and INVCs and that these entities represent a
      subgroup of sinonasal carcinomas relying on SOX2 acquisition during oncogenesis.
      SOX2 amplification appears to identify sinonasal carcinomas that are more likely
      to relapse after primary therapy, suggesting that these patients might benefit
      from a more aggressive therapy regime.

PMID- 23544056
TI  - The impact of study size on meta-analyses: examination of underpowered studies in
      Cochrane reviews.
AB  - BACKGROUND: Most meta-analyses include data from one or more small studies that,
      individually, do not have power to detect an intervention effect. The relative
      influence of adequately powered and underpowered studies in published meta
      analyses has not previously been explored. We examine the distribution of power
      available in studies within meta-analyses published in Cochrane reviews, and
      investigate the impact of underpowered studies on meta-analysis results. METHODS
      AND FINDINGS: For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane
      reviews, we calculated power per study within each meta-analysis. We defined
      adequate power as >=50% power to detect a 30% relative risk reduction. In a
      subset of 1,107 meta-analyses including 5 or more studies with at least two
      adequately powered and at least one underpowered, results were compared with and
      without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all
      included studies were underpowered; only 2,588 (17%) included at least two
      adequately powered studies. 34% of the meta-analyses themselves were adequately
      powered. The median of summary relative risks was 0.75 across all meta-analyses
      (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in
      underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in
      adequately powered studies, in meta-analyses of controlled pharmacological
      trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled
      non-pharmacological trials. The standard error of the intervention effect
      increased by a median of 11% (inter-quartile range -1% to 35%) when underpowered
      studies were omitted; and between-study heterogeneity tended to decrease.
      CONCLUSIONS: When at least two adequately powered studies are available in meta
      analyses reported by Cochrane reviews, underpowered studies often contribute
      little information, and could be left out if a rapid review of the evidence is
      required. However, underpowered studies made up the entirety of the evidence in
      most Cochrane reviews.

PMID- 23544057
TI  - Changes in task-related functional connectivity across multiple spatial scales
      are related to reading performance.
AB  - Reading requires the interaction of a distributed set of cortical areas whose
      distinct patterns give rise to a wide range of individual skill. However, the
      nature of these neural interactions and their relation to reading performance are
      still poorly understood. Functional connectivity analyses of fMRI data can be
      used to characterize the nature of interactivity of distributed brain networks,
      yet most previous studies have focused on connectivity during task-free (i.e.,
      "resting state") conditions. Here, we report new methods for assessing task
      related functional connectivity using data-driven graph theoretical methods and
      describe how large-scale patterns of connectivity relate to individual
      variability in reading performance among children. We found that connectivity
      patterns of subjects performing a reading task could be decomposed hierarchically
      into multiple sub-networks, and we observed stronger long-range interaction
      between sub-networks in subjects with higher task accuracy. Additionally, we
      found a network of hub regions known to be critical to reading that displays
      increased short-range synchronization in higher accuracy subjects. These
      individual differences in task-related functional connectivity reveal that
      increased interaction between distant regions, coupled with selective local
      integration within key regions, is associated with better reading performance.
      Importantly, we show that task-related neuroimaging data contains far more
      information than usually extracted via standard univariate analyses--information
      that can meaningfully relate neural connectivity patterns to cognition and task.

PMID- 23544058
TI  - Bacterial communities associated with the surfaces of fresh fruits and
      vegetables.
AB  - Fresh fruits and vegetables can harbor large and diverse populations of bacteria.
      However, most of the work on produce-associated bacteria has focused on a
      relatively small number of pathogenic bacteria and, as a result, we know far less
      about the overall diversity and composition of those bacterial communities found
      on produce and how the structure of these communities varies across produce
      types. Moreover, we lack a comprehensive view of the potential effects of
      differing farming practices on the bacterial communities to which consumers are
      exposed. We addressed these knowledge gaps by assessing bacterial community
      structure on conventional and organic analogs of eleven store-bought produce
      types using a culture-independent approach, 16 S rRNA gene pyrosequencing. Our
      results demonstrated that the fruits and vegetables harbored diverse bacterial
      communities, and the communities on each produce type were significantly distinct
      from one another. However, certain produce types (i.e., sprouts, spinach,
      lettuce, tomatoes, peppers, and strawberries) tended to share more similar
      communities as they all had high relative abundances of taxa belonging to the
      family Enterobacteriaceae when compared to the other produce types (i.e., apples,
      peaches, grapes, and mushrooms) which were dominated by taxa belonging to the
      Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla. Although
      potentially driven by factors other than farming practice, we also observed
      significant differences in community composition between conventional and organic
      analogs within produce types. These differences were often attributable to
      distinctions in the relative abundances of Enterobacteriaceae taxa, which were
      generally less abundant in organically-grown produce. Taken together, our results
      suggest that humans are exposed to substantially different bacteria depending on
      the types of fresh produce they consume with differences between conventionally
      and organically farmed varieties contributing to this variation.

PMID- 23544059
TI  - Marine mammal strandings and environmental changes: a 15-year study in the St.
      Lawrence ecosystem.
AB  - Understanding the effects of climatic variability on marine mammals is
      challenging due to the complexity of ecological interactions. We used general
      linear models to analyze a 15-year database documenting marine mammal strandings
      (1994-2008; n = 1,193) and nine environmental parameters known to affect marine
      mammal survival, from regional (sea ice) to continental scales (North Atlantic
      Oscillation, NAO). Stranding events were more frequent during summer and fall
      than other seasons, and have increased since 1994. Poor ice conditions observed
      during the same period may have affected marine mammals either directly, by
      modulating the availability of habitat for feeding and breeding activities, or
      indirectly, through changes in water conditions and marine productivity (krill
      abundance). For most species (75%, n = 6 species), a low volume of ice was
      correlated with increasing frequency of stranding events (e.g. R(2)adj = 0.59,
      hooded seal, Cystophora cristata). This likely led to an increase in seal
      mortality during the breeding period, but also to increase habitat availability
      for seasonal migratory cetaceans using ice-free areas during winter. We also
      detected a high frequency of stranding events for mysticete species (minke whale,
      Balaenoptera acutorostrata) and resident species (beluga, Delphinapterus leucas),
      correlated with low krill abundance since 1994. Positive NAO indices were
      positively correlated with high frequencies of stranding events for resident and
      seasonal migratory cetaceans, as well as rare species (R(2)adj = 0.53, 0.81 and
      0.34, respectively). This contrasts with seal mass stranding numbers, which were
      negatively correlated with a positive NAO index. In addition, an unusual multiple
      species mortality event (n = 114, 62% of total annual mortality) in 2008 was
      caused by a harmful algal bloom. Our findings provide an empirical baseline in
      understanding marine mammal survival when faced with climatic variability. This
      is a promising step in integrating stranding records to monitor the consequences
      of environmental changes in marine ecosystems over long time scales.

PMID- 23544060
TI  - Association between age at diagnosis of Graves' disease and variants in genes
      involved in immune response.
AB  - BACKGROUND: Graves' disease (GD) is a complex disease in which genetic
      predisposition is modified by environmental factors. The aim of the study was to
      examine the association between genetic variants in genes encoding proteins
      involved in immune response and the age at diagnosis of GD. METHODS: 735 GD
      patients and 1216 healthy controls from Poland were included into the study.
      Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and
      IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD
      and the association with genotype was analysed. RESULTS: Polymorphism in the HLA
      DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA
      DRB1*03 allele were more frequent in patients with age at GD diagnosis <=30 years
      than in patients with older age at GD diagnosis. CONCLUSIONS: HLADRB1*03 allele
      is associated with young age at diagnosis of Graves' disease in Polish
      population.

PMID- 23544061
TI  - Limitations of augmentation index in the assessment of wave reflection in
      normotensive healthy individuals.
AB  - OBJECTIVES: Augmentation index (AIx) is widely used as a measure of wave
      reflection. We compared the relationship between AIx and age, height and sex with
      'gold standard' measures of wave reflection derived from measurements of pressure
      and flow to establish how well AIx measures wave reflection. MATERIALS AND
      METHODS: Measurements of carotid pressure and flow velocity were made in the
      carotid artery of 65 healthy normotensive individuals (age 21-78 yr; 43 male) and
      pulse wave analysis, wave intensity analysis and wave separation was performed;
      waveforms were classified into type A, B or C. AIx, the time of the first
      shoulder (T(s)), wave reflection index (WRI) and the ratio of backward to forward
      pressure (P(b)/P(f)) were calculated. RESULTS: AIx did not correlate with log WRI
      or P(b)/P(f). When AIx was restricted to positive values AIx and log WRI were
      positively correlated (r = 0.33; p = 0.04). In contrast log WRI and P(b)/P(f)
      were closely correlated (r = 0.66; p<0.001). There was no correlation between the
      T(s) and the timing of Pb or the reflected wave identified by wave intensity
      analysis. Wave intensity analysis showed that the morphology of type C waveforms
      (negative AIx) was principally due to a forward travelling (re-reflected)
      decompression wave in mid-systole. AIx correlated positively with age, inversely
      with height and was higher in women. In contrast log WRI and P(b)/P(f) showed
      negative associations with age, were unrelated to height and did not differ
      significantly by gender. CONCLUSIONS: AIx has serious limitations as a measure of
      wave reflection. Negative AIx values derived from Type C waves should not be used
      as estimates of wave reflection magnitude.

PMID- 23544062
TI  - Universities scale like cities.
AB  - Recent studies of urban scaling show that important socioeconomic city
      characteristics such as wealth and innovation capacity exhibit a nonlinear,
      particularly a power law scaling with population size. These nonlinear effects
      are common to all cities, with similar power law exponents. These findings mean
      that the larger the city, the more disproportionally they are places of wealth
      and innovation. Local properties of cities cause a deviation from the expected
      behavior as predicted by the power law scaling. In this paper we demonstrate that
      universities show a similar behavior as cities in the distribution of the 'gross
      university income' in terms of total number of citations over 'size' in terms of
      total number of publications. Moreover, the power law exponents for university
      scaling are comparable to those for urban scaling. We find that deviations from
      the expected behavior can indeed be explained by specific local properties of
      universities, particularly the field-specific composition of a university, and
      its quality in terms of field-normalized citation impact. By studying both the
      set of the 500 largest universities worldwide and a specific subset of these 500
      universities--the top-100 European universities--we are also able to distinguish
      between properties of universities with as well as without selection of one
      specific local property, the quality of a university in terms of its average
      field-normalized citation impact. It also reveals an interesting observation
      concerning the working of a crucial property in networked systems, preferential
      attachment.

PMID- 23544063
TI  - Unilateral condylar hyperplasia: a 3-dimensional quantification of asymmetry.
AB  - PURPOSE: Objective quantifications of facial asymmetry in patients with
      Unilateral Condylar Hyperplasia (UCH) have not yet been described in literature.
      The aim of this study was to objectively quantify soft-tissue asymmetry in
      patients with UCH and to compare the findings with a control group using a new
      method. MATERIAL AND METHODS: Thirty 3D photographs of patients diagnosed with
      UCH were compared with 30 3D photographs of healthy controls. As UCH presents
      particularly in the mandible, a new method was used to isolate the lower part of
      the face to evaluate asymmetry of this part separately. The new method was
      validated by two observers using 3D photographs of five patients and five
      controls. RESULTS: A significant difference (0.79 mm) between patients and
      controls whole face asymmetry was found. Intra- and inter-observer differences of
      0.011 mm (-0.034-0.011) and 0.017 mm (-0.007-0.042) respectively were found.
      These differences are irrelevant in clinical practice. CONCLUSION: After
      objective quantification, a significant difference was identified in soft-tissue
      asymmetry between patients with UCH and controls. The method used to isolate
      mandibular asymmetry was found to be valid and a suitable tool to evaluate facial
      asymmetry.

PMID- 23544064
TI  - Migration routes and staging areas of trans-Saharan Turtle Doves appraised from
      light-level geolocators.
AB  - The identification of migration routes, wintering grounds and stopover sites are
      crucial issues for the understanding of the Palearctic-African bird migration
      system as well as for the development of relevant conservation strategies for
      trans-Saharan migrants. Using miniaturized light-level geolocators we report a
      comprehensive and detailed year round track of a granivorous trans-Saharan
      migrant, the European Turtle Dove (Streptopelia turtur). From five recovered
      loggers, our data provide new insights on migratory journeys and winter
      destinations of Turtle Doves originating from a breeding population in Western
      France. Data confirm that Turtle Doves wintered in West Africa. The main
      wintering area encompassed Western Mali, the Inner Delta Niger and the
      Malian/Mauritanian border. Some individuals also extended their wintering ranges
      over North Guinea, North-West of Burkina Faso and the Ivory-Coast. Our results
      reveal that all individuals did not spend the winter period at a single location;
      some of them experienced a clear eastward shift of several hundred kilometres. We
      also found evidence for a loop migration pattern, with a post-breeding migration
      flyway lying west of the spring route. Finally, we found that on their way back
      to breeding grounds Turtle Doves needed to refuel after crossing the Sahara
      desert. Contrary to previous suggestions, our data reveal that birds used
      stopover sites for several weeks, presumably in Morocco and North Algeria. This
      later finding is a crucial issue for future conservation strategies because
      environmental conditions on these staging areas might play a pivotal role in
      population dynamics of this declining species.

PMID- 23544065
TI  - Truncated and helix-constrained peptides with high affinity and specificity for
      the cFos coiled-coil of AP-1.
AB  - Protein-based therapeutics feature large interacting surfaces. Protein folding
      endows structural stability to localised surface epitopes, imparting high
      affinity and target specificity upon interactions with binding partners. However,
      short synthetic peptides with sequences corresponding to such protein epitopes
      are unstructured in water and promiscuously bind to proteins with low affinity
      and specificity. Here we combine structural stability and target specificity of
      proteins, with low cost and rapid synthesis of small molecules, towards meeting
      the significant challenge of binding coiled coil proteins in transcriptional
      regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues,
      strategically incorporating i->i+4 helix-inducing constraints, and positioning
      unnatural amino acids, we have produced short, water-stable, alpha-helical
      peptides that bind cFos. A three-dimensional NMR-derived structure for one
      peptide (24) confirmed a highly stable alpha-helix which was resistant to
      proteolytic degradation in serum. These short structured peptides are
      entropically pre-organized for binding with high affinity and specificity to
      cFos, a key component of the oncogenic transcriptional regulator Activator
      Protein-1 (AP-1). They competitively antagonized the cJun-cFos coiled-coil
      interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the
      binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased
      conformational entropy (TDeltaS <=7.5 kcal/mol). This study demonstrates that
      rational design of short peptides constrained by alpha-helical cyclic
      pentapeptide modules is able to retain parental high helicity, as well as high
      affinity and specificity for cFos. These are important steps towards small
      antagonists of the cJun-cFos interaction that mediates gene transcription in
      cancer and inflammatory diseases.

PMID- 23544066
TI  - High-throughput sequencing of small RNA transcriptome reveals salt stress
      regulated microRNAs in sugarcane.
AB  - Salt stress is a primary cause of crop losses worldwide, and it has been the
      subject of intense investigation to unravel the complex mechanisms responsible
      for salinity tolerance. MicroRNA is implicated in many developmental processes
      and in responses to various abiotic stresses, playing pivotal roles in plant
      adaptation. Deep sequencing technology was chosen to determine the small RNA
      transcriptome of Saccharum sp cultivars grown on saline conditions. We
      constructed four small RNAs libraries prepared from plants grown on hydroponic
      culture submitted to 170 mM NaCl and harvested after 1 h, 6 hs and 24 hs. Each
      library was sequenced individually and together generated more than 50 million
      short reads. Ninety-eight conserved miRNAs and 33 miRNAs* were identified by
      bioinformatics. Several of the microRNA showed considerable differences of
      expression in the four libraries. To confirm the results of the bioinformatics
      based analysis, we studied the expression of the 10 most abundant miRNAs and 1
      miRNA* in plants treated with 170 mM NaCl and in plants with a severe treatment
      of 340 mM NaCl. The results showed that 11 selected miRNAs had higher expression
      in samples treated with severe salt treatment compared to the mild one. We also
      investigated the regulation of the same miRNAs in shoots of four cultivars grown
      on soil treated with 170 mM NaCl. Cultivars could be grouped according to miRNAs
      expression in response to salt stress. Furthermore, the majority of the predicted
      target genes had an inverse regulation with their correspondent microRNAs. The
      targets encode a wide range of proteins, including transcription factors,
      metabolic enzymes and genes involved in hormone signaling, probably assisting the
      plants to develop tolerance to salinity. Our work provides insights into the
      regulatory functions of miRNAs, thereby expanding our knowledge on potential salt
      stressed regulated genes.

PMID- 23544067
TI  - The HD-GYP domain protein RpfG of Xanthomonas oryzae pv. oryzicola regulates
      synthesis of extracellular polysaccharides that contribute to biofilm formation
      and virulence on rice.
AB  - Bacterial leaf streak caused by Xanthomonas oryzae pv. oryzicola (Xoc) is one of
      the most important diseases in rice. However, little is known about the
      pathogenicity mechanisms of Xoc. Here we have investigated the function of three
      HD-GYP domain regulatory proteins in biofilm formation, the synthesis of
      virulence factors and virulence of Xoc. Deletion of rpfG resulted in altered
      production of extracellular polysaccharides (EPS), abolished virulence on rice
      and enhanced biofilm formation, but had little effect on the secretion of
      proteases and motility. In contrast, mutational analysis showed that the other
      two HD-GYP domain proteins had no effect on virulence factor synthesis and tested
      phenotypes. Mutation of rpfG led to up-regulation of the type III secretion
      system and altered expression of three putative glycosyltransferase genes gumD,
      pgaC and xagB, which are part of operons directing the synthesis of different
      extracellular polysaccharides. The pgaABCD and xagABCD operons were greatly up
      regulated in the Xoc DeltarpfG mutant, whereas the expression of the gum genes
      was unaltered or slightly enhanced. The elevated biofilm formation of the Xoc
      DeltarpfG mutant was dramatically reduced upon deletion of gumD, xagA and xagB,
      but not when pgaA and pgaC were deleted. Interestingly, only the DeltagumD
      mutant, among these single gene mutants, exhibits multiple phenotype alterations
      including reduced biofilm and EPS production and attenuated virulence on rice.
      These data indicate that RpfG is a global regulator that controls biofilm
      formation, EPS production and bacterial virulence in Xoc and that both gumD- and
      xagB-dependent EPS contribute to biofilm formation under different conditions.

PMID- 23544068
TI  - DNA methylation profiles at precancerous stages associated with recurrence of
      lung adenocarcinoma.
AB  - The aim of this study was to clarify the significance of DNA methylation
      alterations at precancerous stages of lung adenocarcinoma. Using single-CpG
      resolution Infinium array, genome-wide DNA methylation analysis was performed in
      36 samples of normal lung tissue obtained from patients without any primary lung
      tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with
      lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise
      progression of DNA methylation alterations from normal lung tissue to non
      cancerous lung tissue obtained from patients with lung adenocarcinomas, and then
      tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non
      cancerous lung tissue obtained from patients with lung adenocarcinomas was at
      precancerous stages with DNA methylation alterations. At CpG sites of 2,083
      genes, DNA methylation status in samples of non-cancerous lung tissue obtained
      from patients with lung adenocarcinomas was significantly correlated with
      recurrence after establishment of lung adenocarcinomas. Among such recurrence
      related genes, 28 genes are normally unmethylated (average beta-values based on
      Infinium assay in normal lung tissue samples was less than 0.2) and their DNA
      hypermethylation at precancerous stages was strengthened during progression to
      lung adenocarcinomas (Deltabeta(T-N)>0.1). Among these 28 genes, we focused on 6
      for which implications in transcription regulation, apoptosis or cell adhesion
      had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and
      TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza
      2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression
      levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was
      significantly correlated with tumor aggressiveness. These data suggest that DNA
      methylation alterations at precancerous stages determine tumor aggressiveness and
      outcome through silencing of specific genes.

PMID- 23544069
TI  - Heterologous stop codon readthrough of metazoan readthrough candidates in yeast.
AB  - Recent analysis of genomic signatures in mammals, flies, and worms indicates that
      functional translational stop codon readthrough is considerably more abundant in
      metazoa than previously recognized, but this analysis provides only limited clues
      about the function or mechanism of readthrough. If an mRNA known to be read
      through in one species is also read through in another, perhaps these questions
      can be studied in a simpler setting. With this end in mind, we have investigated
      whether some of the readthrough genes in human, fly, and worm also exhibit
      readthrough when expressed in S. cerevisiae. We found that readthrough was
      highest in a gene with a post-stop hexamer known to trigger readthrough, while
      other metazoan readthrough genes exhibit borderline readthrough in S. cerevisiae.

PMID- 23544070
TI  - Human chronotypes from a theoretical perspective.
AB  - The endogenous circadian timing system has evolved to synchronize an organism to
      periodically recurring environmental conditions. Those external time cues are
      called Zeitgebers. When entrained by a Zeitgeber, the intrinsic oscillator adopts
      a fixed phase relation psi to the Zeitgeber. Here, we systematically study how
      the phase of entrainment depends on clock and Zeitgeber properties. We combine
      numerical simulations of amplitude-phase models with predictions from
      analytically tractable models. In this way we derive relations between the phase
      of entrainment psi to the mismatch between the endogenous and Zeitgeber period,
      the Zeitgeber strength, and the range of entrainment. A core result is the "180
      degrees  rule" asserting that the phase psi varies over a range of about 180
      degrees  within the entrainment range. The 180 degrees  rule implies that clocks
      with a narrow entrainment range ("strong oscillators") exhibit quite flexible
      entrainment phases. We argue that this high sensitivity of the entrainment phase
      contributes to the wide range of human chronotypes.

PMID- 23544071
TI  - Networks in a large-scale phylogenetic analysis: reconstructing evolutionary
      history of Asparagales (Lilianae) based on four plastid genes.
AB  - Phylogenetic analysis aims to produce a bifurcating tree, which disregards
      conflicting signals and displays only those that are present in a large
      proportion of the data. However, any character (or tree) conflict in a dataset
      allows the exploration of support for various evolutionary hypotheses. Although
      data-display network approaches exist, biologists cannot easily and routinely use
      them to compute rooted phylogenetic networks on real datasets containing hundreds
      of taxa. Here, we constructed an original neighbour-net for a large dataset of
      Asparagales to highlight the aspects of the resulting network that will be
      important for interpreting phylogeny. The analyses were largely conducted with
      new data collected for the same loci as in previous studies, but from different
      species accessions and greater sampling in many cases than in published analyses.
      The network tree summarised the majority data pattern in the characters of
      plastid sequences before tree building, which largely confirmed the currently
      recognised phylogenetic relationships. Most conflicting signals are at the base
      of each group along the Asparagales backbone, which helps us to establish the
      expectancy and advance our understanding of some difficult taxa relationships and
      their phylogeny. The network method should play a greater role in phylogenetic
      analyses than it has in the past. To advance the understanding of evolutionary
      history of the largest order of monocots Asparagales, absolute diversification
      times were estimated for family-level clades using relaxed molecular clock
      analyses.

PMID- 23544072
TI  - Life history changes in coral fluorescence and the effects of light intensity on
      larval physiology and settlement in Seriatopora hystrix.
AB  - Fluorescence is common in both coral adult and larval stages, and is produced by
      fluorescent proteins that absorb higher energy light and emit lower energy light.
      This study investigated the changes of coral fluorescence in different life
      history stages and the effects of parental light environment on larval
      fluorescence, larval endosymbiotic dinoflagellate abundance, larval size and
      settlement in the brooding coral Seriatopora hystrix. Data showed that coral
      fluorescence changed during development from green in larvae to cyan in adult
      colonies. In larvae, two green fluorescent proteins (GFPs) co-occur where the
      peak emission of one GFP overlaps with the peak excitation of the second GFP
      allowing the potential for energy transfer. Coral larvae showed great variation
      in GFP fluorescence, dinoflagellate abundance, and size. There was no obvious
      relationship between green fluorescence intensity and dinoflagellate abundance,
      green fluorescence intensity and larval size, or dinoflagellate abundance and
      larval size. Larvae of parents from high and low light treatments showed similar
      green fluorescence intensity, yet small but significant differences in size,
      dinoflagellate abundance, and settlement. The large variation in larval
      physiology combined with subtle effects of parental environment on larval
      characteristics seem to indicate that even though adult corals produce larvae
      with a wide range of physiological capacities, these larvae can still show small
      preferences for settling in similar habitats as their parents. These data
      highlight the importance of environmental conditions at the onset of life history
      and parent colony effects on coral larvae.

PMID- 23544073
TI  - SeqEntropy: genome-wide assessment of repeats for short read sequencing.
AB  - BACKGROUND: Recent studies on genome assembly from short-read sequencing data
      reported the limitation of this technology to reconstruct the entire genome even
      at very high depth coverage. We investigated the limitation from the perspective
      of information theory to evaluate the effect of repeats on short-read genome
      assembly using idealized (error-free) reads at different lengths.
      METHODOLOGY/PRINCIPAL FINDINGS: We define a metric H(k) to be the entropy of
      sequencing reads at a read length k and use the relative loss of entropy
      DeltaH(k) to measure the impact of repeats for the reconstruction of whole-genome
      from sequences of length k. In our experiments, we found that entropy loss
      correlates well with de-novo assembly coverage of a genome, and a score of
      DeltaH(k)>1% indicates a severe loss in genome reconstruction fidelity. The
      minimal read lengths to achieve DeltaH(k)<1% are different for various organisms
      and are independent of the genome size. For example, in order to meet the
      threshold of DeltaH(k)<1%, a read length of 60 bp is needed for the sequencing of
      human genome (3.2 10(9) bp) and 320 bp for the sequencing of fruit fly (1.8*10(8)
      bp). We also calculated the DeltaH(k) scores for 2725 prokaryotic chromosomes and
      plasmids at several read lengths. Our results indicate that the levels of repeats
      in different genomes are diverse and the entropy of sequencing reads provides a
      measurement for the repeat structures. CONCLUSIONS/SIGNIFICANCE: The proposed
      entropy-based measurement, which can be calculated in seconds to minutes in most
      cases, provides a rapid quantitative evaluation on the limitation of idealized
      short-read genome sequencing. Moreover, the calculation can be parallelized to
      scale up to large euakryotic genomes. This approach may be useful to tune the
      sequencing parameters to achieve better genome assemblies when a closely related
      genome is already available.

PMID- 23544074
TI  - Dental health in smokers with and without COPD.
AB  - The association between chronic obstructive pulmonary disease (COPD) and
      periodontal disease is sparsely studied. The aim was to describe the co-variation
      of periodontitis and lung function impairment in smokers. The hypothesis was that
      the destructive processes in the mouth and the lungs are interdependent due to a
      general individual susceptibility to detrimental effects of tobacco smoke.
      Smokers with COPD (n = 28) stage II and III according to GOLD guidelines and
      smokers without COPD (n = 29) and healthy non-smokers (n = 23) participated in
      the study. The groups of smokers were matched for cumulative exposure to tobacco
      smoke. Radiographic, general and dental clinical examination, lung function
      measurements and quality of life (SF-36) assessment were conducted. The
      relationship between respiratory and dental outcomes was analyzed. Dental health,
      assessed by plaque, gingival bleeding, periodontal pocket depth and loss of teeth
      was impaired in the smokers compared with non-smokers with no major differences
      between smokers with and without COPD. There was, however, a weak correlation
      between periodontitis and emphysema/impaired diffusion capacity. Impaired quality
      of life was associated with smoking and impaired lung function but not influenced
      by dental status. In conclusion periodontitis was strongly associated with
      smoking, weakly associated with lung tissue destruction and very weakly or even
      not at all associated with chronic airflow limitation. The results indicate that,
      although there was a co-variation between periodontitis and pathologic lung
      processes in smokers, the risk of developing COPD, as defined by spirometric
      outcomes, is not associated with the risk of impaired dental health in smokers.

PMID- 23544075
TI  - IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active
      pulmonary tuberculosis.
AB  - BACKGROUND: Although Type 1 cytokine responses are considered protective in
      pulmonary tuberculosis (PTB), their role as well as those of Type 2, 17 and
      immunoregulatory cytokines in tuberculous lymphadenitis (TBL) and latent
      tuberculosis (LTB) have not been well studied. AIM AND METHODS: To identify
      cytokine responses associated with pulmonary tuberculosis (TB), TB lymphadenitits
      and latent TB, we examined mycobacterial antigen-specific immune responses of
      PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10
      induced Type 1, Type 2 and Type 17 cytokine production and their regulation using
      multiplex ELISA. RESULTS: PTB individuals exhibited a significantly lower
      baseline as well as antigen-specific production of Type 1 (IFNgamma, TNFalpha and
      IL-2); Type 2 (IL-4) and Type 17 (IL-17A and IL-17F) cytokines in comparison to
      both TBL and LTB individuals. TBL individuals exhibited significantly lower
      antigen-specific IFNgamma responses alone in comparison to LTB individuals.
      Although, IL-10 levels were not significantly higher, neutralization of IL-10
      during antigen stimulation resulted in significantly enhanced production of
      IFNgamma, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at
      least partially) the suppression of cytokine responses in PTB. CONCLUSION:
      Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression
      of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of
      these cytokines in the pathogenesis of active TB.

PMID- 23544076
TI  - Lack of systematic topographic difference between attention and reasoning beta
      correlates.
AB  - Based on previous evidence for individual-specific sets of cortical areas active
      during simple attention tasks, in this work we intended to perform within
      individual comparisons of task-induced beta oscillations between visual attention
      and a reasoning task. Since beta induced oscillations are not time-locked to task
      events and were first observed by Fourier transforms, in order to analyze the
      cortical topography of attention induced beta activity, we have previously
      computed corrected-latency averages based on spontaneous peaks of band-pass
      filtered epochs. We then used Independent Component Analysis (ICA) only to single
      out the significant portion of averaged data, above noise levels. In the present
      work ICA served as the main, exhaustive means for decomposing beta activity in
      both tasks, using 128-channel EEG data from 24 subjects. Given the previous
      observed similarity between tasks by visual inspection and by simple descriptive
      statistics, we now intended another approach: to quantify how much each ICA
      component obtained in one task could be explained by a linear combination of the
      topographic patterns from the other task in each individual. Our hypothesis was
      that the major psychological difference between tasks would not be reflected as
      important topographic differences within individuals. Results confirmed the high
      topographic similarity between attention and reasoning beta correlates in that
      few components in each individual were not satisfactorily explained by the
      complementary task, and if those could be considered "task-specific", their scalp
      distribution and estimated cortical sources were not common across subjects.
      These findings, along with those from fMRI studies preserving individual data and
      conventional neuropsychological and neurosurgical observations, are discussed in
      support of a new functional localization hypothesis: individuals use largely
      different sets of cortical association areas to perform a given task, but those
      individual sets do not change importantly across tasks that differ in major
      psychological processes.

PMID- 23544077
TI  - rs12512631 on the group specific complement (vitamin D-binding protein GC)
      implicated in melanoma susceptibility.
AB  - BACKGROUND: Solar radiation should be avoided in melanoma patients. Nevertheless,
      this is the main means by which the body produces vitamin D. Evidence suggests a
      protective role against cancer for vitamin D. Since vitamin D performs its
      function by binding the receptor encoded by the vitamin D-receptor gene (VDR),
      most studies have focused on polymorphisms (SNPs) within this gene. However, the
      gene encoding the vitamin D-binding protein (GC) appears in recent studies as a
      major player in the role of a serum vitamin D level regulator and in Cutaneous
      Melanoma (CM) predisposition. METHODS: We performed a case-control study of 12
      polymorphisms on GC and 9 on VDR among 530 cases and 314 controls from Spanish
      population. RESULTS: We found association between SNP rs12512631, located
      3'downstream of GC, and risk of CM that seems to fit a dominant model (OR 1.63
      95%CI 1.23-2.17 p-value 7*10(-4)). This association remained Bonferroni's
      correction and after adjustment for potential confounders (p-value 3*10(-3)) and
      even after increasing the sample size to 1729 individuals (p-value 0.0129).
      Moreover, we confirmed evidence of an association between CM susceptibility and
      the linkage disequilibrium block marked by tag-SNP rs222016 (p-value 0.032). This
      block covers the GC intron 1 region, with probable regulatory functions.
      CONCLUSION: To our knowledge, this is the first vitamin D pathway-related
      polymorphism study in melanoma risk conducted in the Spanish population.
      Furthermore, we show an association between polymorphisms in GC and melanoma
      risk, confirming recent studies in different populations.

PMID- 23544078
TI  - Constitutive expression of Yes-associated protein (Yap) in adult skeletal muscle
      fibres induces muscle atrophy and myopathy.
AB  - The aim of this study was to investigate the function of the Hippo pathway member
      Yes-associated protein (Yap, gene name Yap1) in skeletal muscle fibres in vivo.
      Specifically we bred an inducible, skeletal muscle fibre-specific knock-in mouse
      model (MCK-tTA-hYAP1 S127A) to test whether the over expression of constitutively
      active Yap (hYAP1 S127A) is sufficient to drive muscle hypertrophy or stimulate
      changes in fibre type composition. Unexpectedly, after 5-7 weeks of constitutive
      hYAP1 S127A over expression, mice suddenly and rapidly lost 20-25% body weight
      and suffered from gait impairments and kyphosis. Skeletal muscles atrophied by 34
      40% and the muscle fibre cross sectional area decreased by ~40% when compared to
      control mice. Histological analysis revealed evidence of skeletal muscle
      degeneration and regeneration, necrotic fibres and a NADH-TR staining resembling
      centronuclear myopathy. In agreement with the histology, mRNA expression of
      markers of regenerative myogenesis (embryonic myosin heavy chain, Myf5, myogenin,
      Pax7) and muscle protein degradation (atrogin-1, MuRF1) were significantly
      elevated in muscles from transgenic mice versus control. No significant changes
      in fibre type composition were detected using ATPase staining. The phenotype was
      largely reversible, as a cessation of hYAP1 S127A expression rescued body and
      muscle weight, restored muscle morphology and prevented further pathological
      progression. To conclude, high Yap activity in muscle fibres does not induce
      fibre hypertrophy nor fibre type changes but instead results in a reversible
      atrophy and deterioration.

PMID- 23544079
TI  - Serum amyloid P is a sialylated glycoprotein inhibitor of influenza A viruses.
AB  - Members of the pentraxin family, including PTX3 and serum amyloid P component
      (SAP), have been reported to play a role in innate host defence against a range
      of microbial pathogens, yet little is known regarding their antiviral activities.
      In this study, we demonstrate that human SAP binds to human influenza A virus
      (IAV) strains and mediates a range of antiviral activities, including inhibition
      of IAV-induced hemagglutination (HA), neutralization of virus infectivity and
      inhibition of the enzymatic activity of the viral neuraminidase (NA).
      Characterization of the anti-IAV activity of SAP after periodate or bacterial
      sialidase treatment demonstrated that alpha(2,6)-linked sialic acid residues on
      the glycosidic moiety of SAP are critical for recognition by the HA of
      susceptible IAV strains. Other proteins of the innate immune system, namely human
      surfactant protein A and porcine surfactant protein D, have been reported to
      express sialylated glycans which facilitate inhibition of particular IAV strains,
      yet the specific viral determinants for recognition of these inhibitors have not
      been defined. Herein, we have selected virus mutants in the presence of human SAP
      and identified specific residues in the receptor-binding pocket of the viral HA
      which are critical for recognition and therefore susceptibility to the antiviral
      activities of SAP. Given the widespread expression of alpha(2,6)-linked sialic
      acid in the human respiratory tract, we propose that SAP may act as an effective
      receptor mimic to limit IAV infection of airway epithelial cells.

PMID- 23544080
TI  - Partial deficiency of sphingosine-1-phosphate lyase confers protection in
      experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: Sphingosine-1-phosphate (S1P) regulates the egress of T cells from
      lymphoid organs; levels of S1P in the tissues are controlled by S1P lyase
      (Sgpl1). Hence, Sgpl1 offers a target to block T cell-dependent inflammatory
      processes. However, the involvement of Sgpl1 in models of disease has not been
      fully elucidated yet, since Sgpl1 KO mice have a short life-span. METHODOLOGY: We
      generated inducible Sgpl1 KO mice featuring partial reduction of Sgpl1 activity
      and analyzed them with respect to sphingolipid levels, T-cell distribution, and
      response in models of inflammation. PRINCIPAL FINDINGS: The partially Sgpl1
      deficient mice are viable but feature profound reduction of peripheral T cells,
      similar to the constitutive KO mice. While thymic T cell development in these
      mice appears normal, mature T cells are retained in thymus and lymph nodes,
      leading to reduced T cell numbers in spleen and blood, with a skewing towards
      increased proportions of memory T cells and T regulatory cells. The therapeutic
      relevance of Sgpl1 is demonstrated by the fact that the inducible KO mice are
      protected in experimental autoimmune encephalomyelitis (EAE). T cell immigration
      into the CNS was found to be profoundly reduced. Since S1P levels in the brain of
      the animals are unchanged, we conclude that protection in EAE is due to the
      peripheral effect on T cells, leading to reduced CNS immigration, rather than on
      local effects in the CNS. SIGNIFICANCE: The data suggest Sgpl1 as a novel
      therapeutic target for the treatment of multiple sclerosis.

PMID- 23544081
TI  - Androgen inhibits abdominal fat accumulation and negatively regulates the PCK1
      gene in male chickens.
AB  - Capons are male chickens whose testes have been surgically incised. Capons show a
      significant increase in fat accumulation compared to intact male chickens.
      However, while caponization leads to a significant reduction in androgen levels
      in roosters, little is known about the molecular mechanisms through which
      androgen status affects lipogenesis in avian species. Therefore, investigation of
      the influence of androgens on fat accumulation in the chicken will provide
      insights into this process. In this study, Affymetrix microarray technology was
      used to analyze the gene expression profiles of livers from capons and intact
      male chickens because the liver is the major site of lipogenesis in avian
      species. Through gene ontology, we found that genes involved in hepatic lipogenic
      biosynthesis were the most highly enriched. Interestingly, among the upregulated
      genes, the cytosolic form of the phosphoenolpyruvate carboxykinase (PCK1) gene
      showed the greatest fold change. Additionally, in conjunction with quantitative
      real-time PCR data, our results suggested that androgen status negatively
      regulated the PCK1 gene in male chickens.

PMID- 23544082
TI  - Foods and dietary patterns that are healthy, low-cost, and environmentally
      sustainable: a case study of optimization modeling for New Zealand.
AB  - OBJECTIVE: Global health challenges include non-communicable disease burdens,
      ensuring food security in the context of rising food prices, and environmental
      constraints around food production, e.g., greenhouse gas [GHG] emissions. We
      therefore aimed to consider optimized solutions to the mix of food items in daily
      diets for a developed country population: New Zealand (NZ). METHODS: We conducted
      scenario development and linear programming to model 16 diets (some with
      uncertainty). Data inputs included nutrients in foods, food prices, food wastage
      and food-specific GHG emissions. FINDINGS: This study identified daily dietary
      patterns that met key nutrient requirements for as little as a median of NZ$ 3.17
      per day (US$ 2.41/d) (95% simulation interval [SI] = NZ$ 2.86 to 3.50/d). Diets
      that included "more familiar meals" for New Zealanders, increased the cost. The
      optimized diets also had low GHG emission profiles compared with the estimate for
      the 'typical NZ diet' e.g., 1.62 kg CO2e/d for one scenario (95%SI = 1.39 to 1.85
      kg CO2e) compared with 10.1 kg CO2e/d, respectively. All of the optimized low
      cost and low-GHG dietary patterns had likely health advantages over the current
      NZ dietary pattern, i.e., lower cardiovascular disease and cancer risk.
      CONCLUSIONS: We identified optimal foods and dietary patterns that would lower
      the risk of non-communicable diseases at low cost and with low greenhouse gas
      emission profiles. These results could help guide central and local government
      decisions around which foods to focus policies on. That is which foods are most
      suitable for: food taxes (additions and exemptions); healthy food vouchers and
      subsidies; and for increased use by public institutions involved in food
      preparation.

PMID- 23544083
TI  - Factors predicting reversion from mild cognitive impairment to normal cognitive
      functioning: a population-based study.
AB  - INTRODUCTION: Mild cognitive impairment (MCI) is associated with an increased
      risk of developing dementia. However, many individuals diagnosed with MCI are
      found to have reverted to normal cognition on follow-up. This study investigated
      factors predicting or associated with reversion from MCI to normal cognition.
      METHODS: Our analyses considered 223 participants (48.9% male) aged 71-89 years,
      drawn from the prospective, population-based Sydney Memory and Ageing Study. All
      were diagnosed with MCI at baseline and subsequently classified with either
      normal cognition or repeat diagnosis of MCI after two years (a further 11
      participants who progressed from MCI to dementia were excluded). Associations
      with reversion were investigated for (1) baseline factors that included
      diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and
      physical and mental health; (2) longitudinal change in potentially modifiable
      factors. RESULTS: There were 66 reverters to normal cognition and 157 non
      reverters (stable MCI). Regression analyses identified diagnostic features as
      most predictive of prognosis, with reversion less likely in participants with
      multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive
      domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p =
      0.031). Reversion was also less likely for participants with arthritis (p =
      0.037), but more likely for participants with higher complex mental activity (p =
      0.003), greater openness to experience (p = 0.041), better vision (p = 0.014),
      better smelling ability (p = 0.040), or larger combined volume of the left
      hippocampus and left amygdala (p<0.040). Reversion was also associated with a
      larger drop in diastolic blood pressure between baseline and follow-up (p =
      0.026). DISCUSSION: Numerous factors are associated with reversion from MCI to
      normal cognition. Assessing these factors could facilitate more accurate
      prognosis of individuals with MCI. Participation in cognitively enriching
      activities and efforts to lower blood pressure might promote reversion.

PMID- 23544084
TI  - Genetic structure of wild bonobo populations: diversity of mitochondrial DNA and
      geographical distribution.
AB  - Bonobos (Pan paniscus) inhabit regions south of the Congo River including all
      areas between its southerly tributaries. To investigate the genetic diversity and
      evolutionary relationship among bonobo populations, we sequenced mitochondrial
      DNA from 376 fecal samples collected in seven study populations located within
      the eastern and western limits of the species' range. In 136 effective samples
      from different individuals (range: 7-37 per population), we distinguished 54
      haplotypes in six clades (A1, A2, B1, B2, C, D), which included a newly
      identified clade (D). MtDNA haplotypes were regionally clustered; 83 percent of
      haplotypes were locality-specific. The distribution of haplotypes across
      populations and the genetic diversity within populations thus showed highly
      geographical patterns. Using population distance measures, seven populations were
      categorized in three clusters: the east, central, and west cohorts. Although
      further elucidation of historical changes in the geological setting is required,
      the geographical patterns of genetic diversity seem to be shaped by
      paleoenvironmental changes during the Pleistocene. The present day riverine
      barriers appeared to have a weak effect on gene flow among populations, except
      for the Lomami River, which separates the TL2 population from the others. The
      central cohort preserves a high genetic diversity, and two unique clades of
      haplotypes were found in the Wamba/Iyondji populations in the central cohort and
      in the TL2 population in the eastern cohort respectively. This knowledge may
      contribute to the planning of bonobo conservation.

PMID- 23544085
TI  - Conditional deletion of Jak2 reveals an essential role in hematopoiesis
      throughout mouse ontogeny: implications for Jak2 inhibition in humans.
AB  - Germline deletion of Jak2 in mice results in embryonic lethality at E12.5 due to
      impaired hematopoiesis. However, the role that Jak2 might play in late gestation
      and postnatal life is unknown. To understand this, we utilized a conditional
      knockout approach that allowed for the deletion of Jak2 at various stages of
      prenatal and postnatal life. Specifically, Jak2 was deleted beginning at either
      mid/late gestation (E12.5), at postnatal day 4 (PN4), or at ~2 months of age.
      Deletion of Jak2 beginning at E12.5 resulted in embryonic death characterized by
      a lack of hematopoiesis. Deletion beginning at PN4 was also lethal due to a lack
      of erythropoiesis. Deletion of Jak2 in young adults was characterized by blood
      cytopenias, abnormal erythrocyte morphology, decreased marrow hematopoietic
      potential, and splenic atrophy. However, death was observed in only 20% of the
      mutants. Further analysis of these mice suggested that the increased
      survivability was due to an incomplete deletion of Jak2 and subsequent re
      population of Jak2 expressing cells, as conditional deletion in mice having one
      floxed Jak2 allele and one null allele resulted in a more severe phenotype and
      subsequent death of all animals. We found that the deletion of Jak2 in the young
      adults had a differential effect on hematopoietic lineages; specifically,
      conditional Jak2 deletion in young adults severely impaired erythropoiesis and
      thrombopoiesis, modestly affected granulopoiesis and monocytopoiesis, and had no
      effect on lymphopoiesis. Interestingly, while the hematopoietic organs of these
      mutant animals were severely affected by the deletion of Jak2, we found that the
      hearts, kidneys, lungs, and brains of these same mice were histologically normal.
      From this, we conclude that Jak2 plays an essential and non-redundant role in
      hematopoiesis during both prenatal and postnatal life and this has direct
      implications regarding the inhibition of Jak2 in humans.

PMID- 23544086
TI  - Prenatal ethanol exposure causes glucose intolerance with increased hepatic
      gluconeogenesis and histone deacetylases in adult rat offspring: reversal by
      tauroursodeoxycholic acid.
AB  - Prenatal ethanol exposure results in increased glucose production in adult rat
      offspring and this may involve modulation of protein acetylation by cellular
      stress. We used adult male offspring of dams given ethanol during gestation days
      1-7 (early), 8-14 (mid) and 15-21 (late) compared with those from control dams. A
      group of ethanol offspring was treated with tauroursodeoxycholic acid (TUDCA) for
      3 weeks. We determined gluconeogenesis, phosphoenolpyruvate carboxykinase
      (PEPCK), glucose-6-phosphatase, hepatic free radicals, histone deacetylases
      (HDAC), acetylated foxo1, acetylated PEPCK, and C/EBP homologous protein as a
      marker of endoplasmic reticulum stress. Prenatal ethanol during either of the 3
      weeks of pregnancy increased gluconeogenesis, gluconeogenic genes, oxidative and
      endoplasmic reticulum stresses, sirtuin-2 and HDAC3, 4, 5, and 7 in adult
      offspring. Conversely, prenatal ethanol reduced acetylation of foxo1 and PEPCK.
      Treatment of adult ethanol offspring with TUDCA reversed all these abnormalities.
      Thus, prenatal exposure of rats to ethanol results in long lasting oxidative and
      endoplasmic reticulum stresses explaining increased expression of gluconeogenic
      genes and HDAC proteins which, by deacetylating foxo1 and PEPCK, contribute to
      increased gluconeogenesis. These anomalies occurred regardless of the time of
      ethanol exposure during pregnancy, including early embryogenesis. As these
      anomalies were reversed by treatment of the adult offspring with TUDCA, this
      compound has therapeutic potentials in the treatment of glucose intolerance
      associated with prenatal ethanol exposure.

PMID- 23544087
TI  - Urban warming drives insect pest abundance on street trees.
AB  - Cities profoundly alter biological communities, favoring some species over
      others, though the mechanisms that govern these changes are largely unknown.
      Herbivorous arthropod pests are often more abundant in urban than in rural areas,
      and urban outbreaks have been attributed to reduced control by predators and
      parasitoids and to increased susceptibility of stressed urban plants. These
      hypotheses, however, leave many outbreaks unexplained and fail to predict
      variation in pest abundance within cities. Here we show that the abundance of a
      common insect pest is positively related to temperature even when controlling for
      other habitat characteristics. The scale insect Parthenolecanium quercifex was 13
      times more abundant on willow oak trees in the hottest parts of Raleigh, NC, in
      the southeastern United States, than in cooler areas, though parasitism rates
      were similar. We further separated the effects of heat from those of natural
      enemies and plant quality in a greenhouse reciprocal transplant experiment. P.
      quercifex collected from hot urban trees became more abundant in hot greenhouses
      than in cool greenhouses, whereas the abundance of P. quercifex collected from
      cooler urban trees remained low in hot and cool greenhouses. Parthenolecanium
      quercifex living in urban hot spots succeed with warming, and they do so because
      some demes have either acclimatized or adapted to high temperatures. Our results
      provide the first evidence that heat can be a key driver of insect pest outbreaks
      on urban trees. Since urban warming is similar in magnitude to global warming
      predicted in the next 50 years, pest abundance on city trees may foreshadow
      widespread outbreaks as natural forests also grow warmer.

PMID- 23544088
TI  - Derivation of multivariate syndromic outcome metrics for consistent testing
      across multiple models of cervical spinal cord injury in rats.
AB  - Spinal cord injury (SCI) and other neurological disorders involve complex
      biological and functional changes. Well-characterized preclinical models provide
      a powerful tool for understanding mechanisms of disease; however managing
      information produced by experimental models represents a significant challenge
      for translating findings across research projects and presents a substantial
      hurdle for translation of novel therapies to humans. In the present work we
      demonstrate a novel 'syndromic' information-processing approach for capitalizing
      on heterogeneous data from diverse preclinical models of SCI to discover
      translational outcomes for therapeutic testing. We first built a large, detailed
      repository of preclinical outcome data from 10 years of basic research on
      cervical SCI in rats, and then applied multivariate pattern detection techniques
      to extract features that are conserved across different injury models. We then
      applied this translational knowledge to derive a data-driven multivariate metric
      that provides a common 'ruler' for comparisons of outcomes across different types
      of injury (NYU/MASCIS weight drop injuries, Infinite Horizons (IH) injuries, and
      hemisection injuries). The findings revealed that each individual endpoint
      provides a different view of the SCI syndrome, and that considering any single
      outcome measure in isolation provides a misleading, incomplete view of the SCI
      syndrome. This limitation was overcome by taking a novel multivariate integrative
      approach for leveraging complex data from preclinical models of neurological
      disease to identify therapies that target multiple outcomes. We suggest that
      applying this syndromic approach provides a roadmap for translating therapies for
      SCI and other complex neurological diseases.

PMID- 23544089
TI  - Some soybean cultivars have ability to induce germination of sunflower broomrape.
AB  - Sunflower broomrape is a noxious parasitic weed which has caused severe damage to
      crop ecosystems. Trap crops can release a mixture of allelochemicals to induce
      the germination of sunflower broomrape. We studied the allelopathic effects of
      soybean on sunflower broomrape. Fourteen common soybean cultivars were grown in
      pots. Samples were collected from soybean plants and rhizosphere soil at five
      growth stages (V1, V3, V5, R2, and R4). The allelopathic effects of soybean
      reached highest at the V3 stage. Methanolic extracts of soybean roots induced
      higher broomrape germination than methanolic extracts of stems or leaves. The
      germination rates induced by root extracts (10-fold dilution) were positively
      correlated with germination rates induced by stem (10-fold dilution) and leaf
      extracts (10-fold dilution). The broomrape germination rates induced by root
      extracts were also positively correlated with soybean nodule diameter and dry
      weight. The results indicated that soybeans could induce sunflower broomrape
      germination. We conclude that soybean has the potential to be used as a trap crop
      for sunflower broomrape.

PMID- 23544091
TI  - Global taxonomic diversity of living reptiles.
AB  - Reptiles are one of the most ecologically and evolutionarily remarkable groups of
      living organisms, having successfully colonized most of the planet, including the
      oceans and some of the harshest and more environmentally unstable ecosystems on
      earth. Here, based on a complete dataset of all the world's diversity of living
      reptiles, we analyse lineage taxonomic richness both within and among clades, at
      different levels of the phylogenetic hierarchy. We also analyse the historical
      tendencies in the descriptions of new reptile species from Linnaeus to March
      2012. Although (non-avian) reptiles are the second most species-rich group of
      amniotes after birds, most of their diversity (96.3%) is concentrated in
      squamates (59% lizards, 35% snakes, and 2% amphisbaenians). In strong contrast,
      turtles (3.4%), crocodilians (0.3%), and tuataras (0.01%) are far less diverse.
      In terms of species discoveries, most turtles and crocodilians were described
      early, while descriptions of lizards, snakes and amphisbaenians are multimodal
      with respect to time. Lizard descriptions, in particular, have reached
      unprecedented levels during the last decade. Finally, despite such remarkably
      asymmetric distributions of reptile taxonomic diversity among groups, we found
      that the distributions of lineage richness are consistently right-skewed, with
      most clades (monophyletic families and genera) containing few lineages
      (monophyletic genera and species, respectively), while only a few have radiated
      greatly (notably the families Colubridae and Scincidae, and the lizard genera
      Anolis and Liolaemus). Therefore, such consistency in the frequency distribution
      of richness among clades and among phylogenetic levels suggests that the nature
      of reptile biodiversity is fundamentally fractal (i.e., it is scale invariant).
      We then compared current reptile diversity with the global reptile diversity and
      taxonomy known in 1980. Despite substantial differences in the taxonomies
      (relative to 2012), the patterns of lineage richness remain qualitatively
      identical, hence reinforcing our conclusions about the fractal nature of reptile
      biodiversity.

PMID- 23544090
TI  - Transcriptional profiling of rice early response to Magnaporthe oryzae identified
      OsWRKYs as important regulators in rice blast resistance.
AB  - Rice blast disease is a major threat to rice production worldwide, but the
      mechanisms underlying rice resistance to the causal agent Magnaporthe oryzae
      remain elusive. Therefore, we carried out a transcriptome study on rice early
      defense response to M. oryzae. We found that the transcriptional profiles of rice
      compatible and incompatible interactions with M. oryzae were mostly similar, with
      genes regulated more prominently in the incompatible interactions. The functional
      analysis showed that the genes involved in signaling and secondary metabolism
      were extensively up-regulated. In particular, WRKY transcription factor genes
      were significantly enriched among the up-regulated genes. Overexpressing one of
      these WRKY genes, OsWRKY47, in transgenic rice plants conferred enhanced
      resistance against rice blast fungus. Our results revealed the sophisticated
      transcriptional reprogramming of signaling and metabolic pathways during rice
      early response to M. oryzae and demonstrated the critical roles of WRKY
      transcription factors in rice blast resistance.

PMID- 23544092
TI  - Cunnilingus apparently increases duration of copulation in the Indian flying fox,
      Pteropus giganteus.
AB  - We observed a total of 57 incidences of copulation in a colony of the Indian
      flying fox, Pteropus giganteus, over 13 months under natural conditions. The
      colony consisted of about 420 individuals, roosting in a Ficus religiosa tree.
      Copulations occurred between 07.00 h and 09.30 h from July to January, with more
      occurring in October and November. Initially males groomed their penis before
      approaching a nearby female. Females typically moved away and males followed.
      When the female stopped moving, the male started licking her vagina
      (cunnilingus). Typically each bout of cunnilingus lasted for about 50 s. In 57
      out of 69 observations, the male mounted the female and copulated. The duration
      of copulation varied from 10 to 20 sec. After completion of copulation, the male
      continued cunnilingus for 94 to 188 sec. The duration of pre-copulatory
      cunnilingus and copulation was positively correlated whereas, the duration of pre
      and post-copulatory cunnilingus was negatively correlated. Apart from humans,
      oral sex as foreplay prior to copulation is uncommon in mammals. Another
      pteropodid bat, Cynopterus sphinx exhibits fellatio with females licking the
      penis of males during copulation. It appears that bats, especially pteropodids
      perform oral sex, either cunnilingus or fellatio, possibly for achieving longer
      copulation.

PMID- 23544093
TI  - Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre
      eclampsia.
AB  - The primary mechanism underlying pre-eclampsia (PE) remains one of the most
      burning problems in the obstetrics and gynecology. In this study, we performed an
      expression profiling screen and detected 1312 genes that were differentially
      expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and
      SH3PXD2A. After validating the microarray results, we conducted the quantitative
      methylation analysis of LEP and SH3PXD2A in preeclamptic (n = 16) versus normal
      placentas (n = 16). Our results showed that many CpG sites close to the
      transcriptional start site (TSS) of LEP gene were hypomethylated in placentas
      from pregnancies with PE compared with those of in controls, including the TSS
      position (p = 0.001), the binding sites of Sp1 (p = 1.57*10(-4)), LP1 (p = 0.023)
      and CEBPalpha (p = 0.031). Luciferase reporter analysis confirmed the aberrant
      methylation of LEP promoter and CEBPalpha co-transfection had a role in the
      regulation of gene expression. Our results indicated the aberrant LEP promoter
      methylation was involved in the development of PE. We did not find a significant
      methylation differences between groups in the promoter region of SH3PXD2A,
      however, a CGI region in the gene body (CGI34) presented a higher methylation in
      preeclamptic placentas (p = 1.57*10(-4)), which might promote the efficiency of
      gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis
      of PE through its role in the regulation of trophoblast cell invasion in the
      period of placenta formation.

PMID- 23544094
TI  - Plasmodium berghei MAPK1 displays differential and dynamic subcellular
      localizations during liver stage development.
AB  - Mitogen-activated protein kinases (MAPKs) regulate key signaling events in
      eukaryotic cells. In the genomes of protozoan Plasmodium parasites, the causative
      agents of malaria, two genes encoding kinases with significant homology to other
      eukaryotic MAPKs have been identified (mapk1, mapk2). In this work, we show that
      both genes are transcribed during Plasmodium berghei liver stage development, and
      analyze expression and subcellular localization of the PbMAPK1 protein in liver
      stage parasites. Live cell imaging of transgenic parasites expressing GFP-tagged
      PbMAPK1 revealed a nuclear localization of PbMAPK1 in the early schizont stage
      mediated by nuclear localization signals in the C-terminal domain. In contrast, a
      distinct localization of PbMAPK1 in comma/ring-shaped structures in proximity to
      the parasite's nuclei and the invaginating parasite membrane was observed during
      the cytomere stage of parasite development as well as in immature blood stage
      schizonts. The PbMAPK1 localization was found to be independent of integrity of a
      motif putatively involved in ATP binding, integrity of the putative activation
      motif and the presence of a predicted coiled-coil domain in the C-terminal
      domain. Although PbMAPK1 knock out parasites showed normal liver stage
      development, the kinase may still fulfill a dual function in both schizogony and
      merogony of liver stage parasites regulated by its dynamic and stage-dependent
      subcellular localization.

PMID- 23544095
TI  - Light-emitting channelrhodopsins for combined optogenetic and chemical-genetic
      control of neurons.
AB  - Manipulation of neuronal activity through genetically targeted actuator molecules
      is a powerful approach for studying information flow in the brain. In these
      approaches the genetically targeted component, a receptor or a channel, is
      activated either by a small molecule (chemical genetics) or by light from a
      physical source (optogenetics). We developed a hybrid technology that allows
      control of the same neurons by both optogenetic and chemical genetic means. The
      approach is based on engineered chimeric fusions of a light-generating protein
      (luciferase) to a light-activated ion channel (channelrhodopsin). Ionic currents
      then can be activated by bioluminescence upon activation of luciferase by its
      substrate, coelenterazine (CTZ), as well as by external light. In cell lines,
      expression of the fusion of Gaussia luciferase to Channelrhodopsin-2 yielded
      photocurrents in response to CTZ. Larger photocurrents were produced by fusing
      the luciferase to Volvox Channelrhodopsin-1. This version allowed chemical
      modulation of neuronal activity when expressed in cultured neurons: CTZ treatment
      shifted neuronal responses to injected currents and sensitized neurons to fire
      action potentials in response to subthreshold synaptic inputs. These luminescent
      channelrhodopsins--or luminopsins--preserve the advantages of light-activated ion
      channels, while extending their capabilities. Our proof-of-principle results
      suggest that this novel class of tools can be improved and extended in numerous
      ways.

PMID- 23544096
TI  - Responses of phosphate transporter gene and alkaline phosphatase in Thalassiosira
      pseudonana to phosphine.
AB  - Phosphine, which is released continuously from sediment, can affect the eco
      physiological strategies and molecular responses of phytoplankton. To examine the
      effects of phosphine on phosphorus uptake and utilization in Thalassiosira
      pseudonana, we examined the transcriptional level of the phosphate transporter
      gene (TpPHO) and the activity of alkaline phosphatase (AKP) in relation to
      supplement of various concentrations of phosphine. TpPHO expression was markedly
      promoted by phosphine in both the phosphate-deficient and phosphate-4 uM culture.
      However, high phosphine concentrations can inhibit TpPHO transcription in the
      declining growth phase. AKP activity was also higher in the phosphine treatment
      groups than that of the control. It increased with increasing phosphine
      concentration in the range of 0 to 0.056 uM but was inhibited by higher levels of
      phosphine. These responses revealed that phosphine can affect phosphate uptake
      and utilization in T. pseudonana. This result was consistent with the effect of
      phosphine on algal growth, while TpPHO expression and AKP were even more
      sensitive to phosphine than algal growth. This work provides a basic
      understanding for further research about how phosphine affects phytoplankton.

PMID- 23544098
TI  - Possible interbreeding in late Italian Neanderthals? New data from the Mezzena
      jaw (Monti Lessini, Verona, Italy).
AB  - In this article we examine the mandible of Riparo Mezzena a Middle Paleolithic
      rockshelter in the Monti Lessini (NE Italy, Verona) found in 1957 in association
      with Charentian Mousterian lithic assemblages. Mitochondrial DNA analysis
      performed on this jaw and on other cranial fragments found at the same
      stratigraphic level has led to the identification of the only genetically typed
      Neanderthal of the Italian peninsula and has confirmed through direct dating that
      it belongs to a late Neanderthal. Our aim here is to re-evaluate the taxonomic
      affinities of the Mezzena mandible in a wide comparative framework using both
      comparative morphology and geometric morphometrics. The comparative sample
      includes mid-Pleistocene fossils, Neanderthals and anatomically modern humans.
      This study of the Mezzena jaw shows that the chin region is similar to that of
      other late Neanderthals which display a much more modern morphology with an
      incipient mental trigone (e.g. Spy 1, La Ferrassie, Saint-Cesaire). In our view,
      this change in morphology among late Neanderthals supports the hypothesis of
      anatomical change of late Neanderthals and the hypothesis of a certain degree of
      interbreeding with AMHs that, as the dating shows, was already present in the
      European territory. Our observations on the chin of the Mezzena mandible lead us
      to support a non abrupt phylogenetic transition for this period in Europe.

PMID- 23544097
TI  - Polyanionic candidate microbicides accelerate the formation of semen-derived
      amyloid fibrils to enhance HIV-1 infection.
AB  - Polyanionic candidate microbicides, including cellulose sulfate, carrageenan, PRO
      2000, were proven ineffective in preventing HIV-1 transmission and even cellulose
      sulfate showed increased risk of HIV acquisition in the Phase III efficacy
      trials. Semen plays critical roles in HIV-1 sexual transmission. Specifically,
      amyloid fibrils formed by fragments of prostatic acidic phosphatase (PAP) in
      semen termed semen-derived enhancer of virus infection (SEVI) could drastically
      enhance HIV-1 infection. Here we investigated the interaction between polyanions
      and PAP248-286, a prototype peptide of SEVI, to understand the possible cause of
      polyanionic candidate microbicides to fail in clinical trials. We found anionic
      polymers could efficiently promote SEVI fibril formation, most likely mediated by
      the natural electrostatic interaction between polyanions and PAP248-286, as
      revealed by acid native PAGE and Western blot. The overall anti-HIV-1 activity of
      polyanions in the presence or absence of PAP248-286 or semen was evaluated. In
      the viral infection assay, the supernatants of polyanions/PAP248-286 or
      polyanions/semen mixtures containing the free, unbound polyanionic molecules
      showed a general reduction in antiviral efficacy, while the pellets containing
      amyloid fibrils formed by the polyanion-bound PAP248-286 showed aggravated
      enhancement of viral infection. Collectively, from the point of drug-host protein
      interaction, our study revealed that polyanions facilitate SEVI fibril formation
      to promote HIV-1 infection, thus highlighting a molecular mechanism underlying
      the failure of polyanions in clinical trials and the importance of drug-semen
      interaction in evaluating the anti-HIV-1 efficacy of candidate microbicides.

PMID- 23544099
TI  - Head-mounted eye tracking of a chimpanzee under naturalistic conditions.
AB  - This study offers a new method for examining the bodily, manual, and eye
      movements of a chimpanzee at the micro-level. A female chimpanzee wore a
      lightweight head-mounted eye tracker (60 Hz) on her head while engaging in daily
      interactions with the human experimenter. The eye tracker recorded her eye
      movements accurately while the chimpanzee freely moved her head, hands, and body.
      Three video cameras recorded the bodily and manual movements of the chimpanzee
      from multiple angles. We examined how the chimpanzee viewed the experimenter in
      this interactive setting and how the eye movements were related to the ongoing
      interactive contexts and actions. We prepared two experimentally defined contexts
      in each session: a face-to-face greeting phase upon the appearance of the
      experimenter in the experimental room, and a subsequent face-to-face task phase
      that included manual gestures and fruit rewards. Overall, the general viewing
      pattern of the chimpanzee, measured in terms of duration of individual fixations,
      length of individual saccades, and total viewing duration of the experimenter's
      face/body, was very similar to that observed in previous eye-tracking studies
      that used non-interactive situations, despite the differences in the experimental
      settings. However, the chimpanzee viewed the experimenter and the scene objects
      differently depending on the ongoing context and actions. The chimpanzee viewed
      the experimenter's face and body during the greeting phase, but viewed the
      experimenter's face and hands as well as the fruit reward during the task phase.
      These differences can be explained by the differential bodily/manual actions
      produced by the chimpanzee and the experimenter during each experimental phase
      (i.e., greeting gestures, task cueing). Additionally, the chimpanzee's viewing
      pattern varied depending on the identity of the experimenter (i.e., the
      chimpanzee's prior experience with the experimenter). These methods and results
      offer new possibilities for examining the natural gaze behavior of chimpanzees.

PMID- 23544100
TI  - Evolutionary thinking in microeconomic models: prestige bias and market bubbles.
AB  - Evolutionary models broadly support a number of social learning strategies likely
      important in economic behavior. Using a simple model of price dynamics, I show
      how prestige bias, or copying of famed (and likely successful) individuals,
      influences price equilibria and investor disposition in a way that exacerbates or
      creates market bubbles. I discuss how integrating the social learning and
      demographic forces important in cultural evolution with economic models provides
      a fruitful line of inquiry into real-world behavior.

PMID- 23544101
TI  - Cultural adaptation of a survey to assess medical providers' knowledge of and
      attitudes towards HIV/AIDS in Albania.
AB  - Though the HIV/AIDS epidemic in Southeastern Europe is one of low reported
      prevalence, numerous studies have described the pervasiveness of medical
      providers' lack of knowledge of HIV/AIDS in the Balkans. This study sought to
      culturally adapt an instrument to assess medical providers' knowledge of and
      attitudes towards HIV/AIDS in Albania. Cultural adaptation was completed through
      development of a survey from previously validated instruments, translation of the
      survey into Albanian, blinded back translation, expert committee review of the
      draft instrument, focus group pre-testing with community- and University Hospital
      Center of Tirana-based physicians and nurses, and test-retest reliability
      testing. Blinded back translation of the instrument supported the initial
      translation with slight changes to the idiomatic and conceptual equivalences.
      Focus group pre-testing generally supported the instrument, yet some experiential
      and idiomatic changes were implemented. Based on unweighted kappa and/or
      prevalence adjusted bias adjusted kappa (PABAK), 20 of the 43 questions were
      deemed statistically significant at kappa and/or PABAK >=0.5, while 12 others did
      not cross zero on the 95% confidence interval for kappa, indicating their
      probable significance. Subsequently, an instrument to assess medical providers'
      knowledge of and attitudes toward HIV/AIDS for an Albanian population was
      developed which can be expanded within Albania and potentially to other countries
      within the Balkans, which have an Albanian-speaking population.

PMID- 23544102
TI  - Interactions between genetic variants in AMH and AMHR2 may modify age at natural
      menopause.
AB  - The onset of menopause has important implications on women's fertility and
      health. We previously identified genetic variants in genes involved in initial
      follicle recruitment as potential modifiers of age at natural menopause. The
      objective of this study was to extend our previous study, by searching for
      pairwise interactions between tagging single nucleotide polymorphisms (tSNPs) in
      the 5 genes previously selected (AMH, AMHR2, BMP15, FOXL2, GDF9). We performed a
      cross-sectional study among 3445 women with a natural menopause participating in
      the Prospect-EPIC study, a population-based prospective cohort study, initiated
      between 1993 and 1997. Based on the model-based multifactor dimensionality
      reduction (MB-MDR) test with a permutation-based maxT correction for multiple
      testing, we found a statistically significant interaction between rs10407022 in
      AMH and rs11170547 in AMHR2 (p = 0.019) associated with age at natural menopause.
      Rs10407022 did not have a statistically significant main effect. However,
      rs10407022 is an eQTL SNP that has been shown to influence mRNA expression levels
      in lymphoblastoid cell lines. This study provides additional insights into the
      genetic background of age at natural menopause and suggests a role of the AMH
      signaling pathway in the onset of natural menopause. However, these results
      remain suggestive and replication by independent studies is necessary.

PMID- 23544103
TI  - Population structure and the colonization route of one of the oldest North
      American invasive insects: stories from the worn road of the Hessian fly,
      Mayetiola destructor (Say).
AB  - An integral part to understanding the biology of an invasive species is
      determining its origin, particularly in pest species. As one of the oldest known
      invasive species, the goals of this study were to evaluate the evidence of a
      westward expansion of Hessian fly into North America, from a potential singular
      introduction event, and the population genetic structure of current populations.
      Levels of genetic diversity and population structure in the Hessian fly were
      compared across North America, Europe, North Africa, Western Asia, and New
      Zealand. Furthermore, Old World populations were evaluated as possible sources of
      introduction. We tested diversity and population structure by examining 18
      microsatellite loci with coverage across all four Hessian fly chromosomes.
      Neither genetic diversity nor population genetic structure provided evidence of a
      westward movement from a single introduction in North America. Introduced
      populations in North America did not show identity or assignment to any Old World
      population, likely indicating a multiple introduction scenario with subsequent
      gene flow between populations. Diversity and selection were assessed on a
      chromosomal level, with no differences in diversity or selection between
      chromosomes or between native and introduced populations.

PMID- 23544104
TI  - Open-source 3D-printable optics equipment.
AB  - Just as the power of the open-source design paradigm has driven down the cost of
      software to the point that it is accessible to most people, the rise of open
      source hardware is poised to drive down the cost of doing experimental science to
      expand access to everyone. To assist in this aim, this paper introduces a library
      of open-source 3-D-printable optics components. This library operates as a
      flexible, low-cost public-domain tool set for developing both research and
      teaching optics hardware. First, the use of parametric open-source designs using
      an open-source computer aided design package is described to customize the optics
      hardware for any application. Second, details are provided on the use of open
      source 3-D printers (additive layer manufacturing) to fabricate the primary
      mechanical components, which are then combined to construct complex optics
      related devices. Third, the use of the open-source electronics prototyping
      platform are illustrated as control for optical experimental apparatuses. This
      study demonstrates an open-source optical library, which significantly reduces
      the costs associated with much optical equipment, while also enabling relatively
      easily adapted customizable designs. The cost reductions in general are over 97%,
      with some components representing only 1% of the current commercial investment
      for optical products of similar function. The results of this study make its
      clear that this method of scientific hardware development enables a much broader
      audience to participate in optical experimentation both as research and teaching
      platforms than previous proprietary methods.

PMID- 23544105
TI  - Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma:
      a meta-analysis of randomized placebo-controlled trials.
AB  - BACKGROUND: Interleukin (IL)-5 is believed to be a key cytokine in eosinophil
      inflammatory infiltration in asthma. Previous clinical trials have evaluated the
      efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in
      patients with asthma. However, most of these studies were small, the conclusions
      were inconsistent, and the precise effects are therefore debatable. METHODS: A
      meta-analysis of randomized placebo-controlled trials was conducted to evaluate
      the effect of intravenous infusion of mepolizumab on clinical outcomes in
      patients with asthma. Trials were searched in PubMed, Embase, Web of Science,
      Cochrane CENTRAL, Scopus, reviews, and reference lists of relevant articles. The
      outcome variables analyzed included eosinophil counts in blood and sputum,
      airways outcome measures, exacerbations, asthma control, and quality of life
      scores. RESULTS: Seven studies met final inclusion criteria (total n = 1131).
      From the pooled analyses, mepolizumab significantly reduced eosinophils in blood
      (MD -0.29*10(9)/L, 95% CI -0.44 to -0.14*10(9)/L, P = 0.0001) and sputum (MD 
      6.05%, 95% CI -9.34 to -2.77%, P = 0.0003). Mepolizumab was also associated with
      significantly decreased exacerbation risk than placebo (OR 0.30, 95%CI 0.13 to
      0.67, P = 0.004), and with a significant improvement in the scores on the Asthma
      Quality of Life Questionnaire (AQLQ) (MD 0.26, 95% CI 0.03 to 0.49, P = 0.03) in
      patients with eosinophilic asthma. There were no statistical differences between
      the groups with respect to FEV1, PEF, or histamine PC20 (all P>0.05), and a non
      significant trend for improvement in scores on the Juniper Asthma Control
      Questionnaire (JACQ) (MD -0.21, 95% CI -0.43 to 0.01, P = 0.06) in the
      mepolizumab group was observed. CONCLUSIONS: Mepolizumab reduces the risk of
      exacerbations and improves quality of life in patients with eosinophilic asthma,
      but no significant improvement in lung function outcomes was observed. Further
      research is required to establish the possible role of anti-IL-5 as a therapy for
      asthma.

PMID- 23544106
TI  - The influence of 150-cavity binders on the dynamics of influenza A neuraminidases
      as revealed by molecular dynamics simulations and combined clustering.
AB  - Neuraminidase inhibitors are the main pharmaceutical agents employed for
      treatments of influenza infections. The neuraminidase structures typically
      exhibit a 150-cavity, an exposed pocket that is adjacent to the catalytic site.
      This site offers promising additional contact points for improving potency of
      existing pharmaceuticals, as well as generating entirely new candidate
      inhibitors. Several inhibitors based on known compounds and designed to interact
      with 150-cavity residues have been reported. However, the dynamics of any of
      these inhibitors remains unstudied and their viability remains unknown. This work
      reports the outcome of long-term, all-atom molecular dynamics simulations of four
      such inhibitors, along with three standard inhibitors for comparison. Each is
      studied in complex with four representative neuraminidase structures, which are
      also simulated in the absence of ligands for comparison, resulting in a total
      simulation time of 9.6 us. Our results demonstrate that standard inhibitors
      characteristically reduce the mobility of these dynamic proteins, while the 150
      binders do not, instead giving rise to many unique conformations. We further
      describe an improved RMSD-based clustering technique that isolates these
      conformations--the structures of which are provided to facilitate future
      molecular docking studies--and reveals their interdependence. We find that this
      approach confers many advantages over previously described techniques, and the
      implications for rational drug design are discussed.

PMID- 23544107
TI  - Quantitative phenotyping of Duchenne muscular dystrophy dogs by comprehensive
      gait analysis and overnight activity monitoring.
AB  - The dystrophin-deficient dog is excellent large animal model for testing novel
      therapeutic modalities for Duchenne muscular dystrophy (DMD). Despite well
      documented descriptions of dystrophic symptoms in these dogs, very few
      quantitative studies have been performed. Here, we developed a comprehensive set
      of non-invasive assays to quantify dog gait (stride length and speed), joint
      angle and limb mobility (for both forelimb and hind limb), and spontaneous
      activity at night. To validate these assays, we examined three 8-m-old mix-breed
      dystrophic dogs. We also included three age-matched siblings as the normal
      control. High-resolution video recorders were used to digitize dog walking and
      spontaneous movement at night. Stride speed and length were significantly
      decreased in affected dogs. The mobility of the limb segments (forearm, front
      foot, lower thigh, rear foot) and the carpus and hock joints was significantly
      reduced in dystrophic dogs. There was also a significant reduction of the
      movement in affected dogs during overnight monitoring. In summary, we have
      established a comprehensive set of outcome measures for clinical phenotyping of
      DMD dogs. These non-invasive end points would be valuable in monitoring disease
      progression and therapeutic efficacy in translational studies in the DMD dog
      model.

PMID- 23544108
TI  - Symptomatic menopausal transition increases the risk of new-onset depressive
      disorder in later life: a nationwide prospective cohort study in Taiwan.
AB  - INTRODUCTION: The role of the menopausal transition and associated menopausal
      symptoms in the occurrence of depressive disorders has been discussed and debated
      for a long time. Most previous clinical studies had limited case samples, and did
      not control the attributable risk of medical comorbidities. METHODS: Patients
      with a diagnosis of symptomatic menopausal transition and without a psychiatric
      history were enrolled in 2000 in Taiwan, and compared with age-matched controls
      (1?4). These subjects were followed to the end of 2010 to investigate the
      association between symptomatic menopausal transition and new-onset depressive
      disorder; the effect of medical comorbidities was also assessed. RESULTS: A total
      of 5,837 women with symptomatic menopausal transition were identified, and
      compared with 23,348 age-matched controls in 2000. The follow-up showed that
      symptomatic menopausal transition was an independent risk factor for major
      depression (hazard ratio[HR]: 2.18, 95%CI: 1.79~2.65) and any depressive disorder
      (HR: 2.34, 95%CI: 2.08~2.63) after adjusting age at enrollment, monthly income,
      residence location, level of urbanization, and comorbid medical diseases. In
      addition, medical comorbidities, including cerebrovascular disease (HR: 1.77, 95%
      CI: 1.52~2.07), cardiovascular diseases (HR: 1.35, 95% CI: 1.15~1.57), congestive
      heart failure (HR: 1.35, 95% CI: 1.04~1.75), and liver diseases (HR: 1.19, 95%
      CI: 1.03~1.36) increased the risk of developing any depressive disorder.
      CONCLUSION: Our population cohort study, with the largest study sample and
      medical record diagnosis thus far, supports an association between symptomatic
      menopausal transition and depressive disorder in midlife women, and an increased
      risk of depressive disorder with medical comorbidities.

PMID- 23544109
TI  - The role of proteasome beta subunits in gastrin-mediated transcription of
      plasminogen activator inhibitor-2 and regenerating protein1.
AB  - The hormone gastrin physiologically regulates gastric acid secretion and also
      contributes to maintaining gastric epithelial architecture by regulating
      expression of genes such as plasminogen activator inhibitor 2 (PAI-2) and
      regenerating protein 1 (Reg1). Here we examine the role of proteasome subunit
      PSMB1 in the transcriptional regulation of PAI-2 and Reg1 by gastrin, and its
      subcellular distribution during gastrin stimulation. We used the gastric cancer
      cell line AGS, permanently transfected with the CCK2 receptor (AGS-GR) to study
      gastrin stimulated expression of PAI-2 and Reg1 reporter constructs when PSMB1
      was knocked down by siRNA. Binding of PSMB1 to the PAI-2 and Reg1 promoters was
      assessed by chromatin immunoprecipitation (ChIP) assay. Subcellular distribution
      of PSMB1 was determined by immunocytochemistry and Western Blot. Gastrin robustly
      increased expression of PAI-2 and Reg1 in AGS-GR cells, but when PSMB1 was
      knocked down the responses were dramatically reduced. In ChIP assays, following
      immunoprecipitation of chromatin with a PSMB1 antibody there was a substantial
      enrichment of DNA from the gastrin responsive regions of the PAI-2 and Reg1
      promoters compared with chromatin precipitated with control IgG. In AGS-GR cells
      stimulated with gastrin there was a significant increase in the ratio of
      nuclear:cytoplasmic PSMB1 over the same timescale as recruitment of PSMB1 to the
      PAI-2 and Reg1 promoters seen in ChIP assays. We conclude that PSMB1 is part of
      the transcriptional machinery required for gastrin stimulated expression of PAI-2
      and Reg1, and that its change in subcellular distribution in response to gastrin
      is consistent with this role.

PMID- 23544111
TI  - Selective leptin insensitivity and alterations in female-reproductive patterns
      linked to hyperleptinemia during infancy.
AB  - The dramatic increase in the prevalence of childhood obesity worldwide makes the
      investigation of its early developmental stages and effective prevention
      strategies an urgent issue. CCK1 deficient OLETF rats are a model of obesity
      previously used to study the early phases of this disorder. Here, we exposed wild
      type (LETO) females to an early obesogenic environment and genetically obese
      OLETF females to a lean postnatal environment, to assess long term alterations in
      leptin sensitivity, predisposition to diet induced obesity and adult female
      health. We found that genetically lean females reared by obese mothers presented
      early postnatal hyperleptemia, selectively reduced response to leptin and
      sensitivity to diet induced obesity when exposed to a high palatable diet as
      adults. The estrous cycle structure and intake profile were permanently
      disrupted, despite presenting normal adiposity/body weight/food intake.
      Genetically obese females reared by lean dams showed normalized early levels of
      leptin and reduced body weight, food intake and body fat at adulthood; normalized
      estrous cycle structure and food intake across the cycle, improved hormonal
      profile and peripheral leptin sensitivity and a remarkable progress in self
      control when exposed to a high fat/palatable diet. Altogether, it appears that
      the early postnatal environment plays a critical role in determining later life
      coping with metabolic challenges and has an additive effect on the genetic
      predisposition that makes OLETF females morbidly obese as adults. This work also
      links, for the first time, alterations in the leptin system during early
      development to later life abnormalities related to female reproduction and
      health.

PMID- 23544110
TI  - Increased antigen specific T cell numbers in the absence of altered migration or
      division rates as a result of mucosal cholera toxin administration.
AB  - Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune
      responses to co-administered antigens following oral or intranasal immunization
      of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell
      migration and proliferation profiles in vivo is not well characterized. In this
      study, the effect of CT on the migration pattern and proliferative responses of
      adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally
      vaccinated mice, was analyzed by flow cytometry. GFP-expressing or CFSE-labeled
      OT-II lymphocytes were adoptively transferred to naive C57BL/6 mice, and mice
      were subsequently vaccinated with OVA with or without CT via the oral or
      intranasal route. CT did not alter the migration pattern of antigen-specific T
      cells, regardless of the route of immunization, but increased the number of
      transgenic CD4(+) T cells in draining lymphoid tissue. This increase in the
      number of transgenic CD4(+) T cells was not due to cells undergoing more rounds
      of cellular division in vivo, suggesting that CT may exert an indirect adjuvant
      effect on CD4(+) T cells. The findings reported here suggest that CT functions as
      a mucosal adjuvant by increasing the number of antigen specific CD4(+) T cells
      independent of their migration pattern or kinetics of cellular division.

PMID- 23544112
TI  - From models to measurements: comparing downed dead wood carbon stock estimates in
      the U.S. forest inventory.
AB  - The inventory and monitoring of coarse woody debris (CWD) carbon (C) stocks is an
      essential component of any comprehensive National Greenhouse Gas Inventory
      (NGHGI). Due to the expense and difficulty associated with conducting field
      inventories of CWD pools, CWD C stocks are often modeled as a function of more
      commonly measured stand attributes such as live tree C density. In order to
      assess potential benefits of adopting a field-based inventory of CWD C stocks in
      lieu of the current model-based approach, a national inventory of downed dead
      wood C across the U.S. was compared to estimates calculated from models
      associated with the U.S.'s NGHGI and used in the USDA Forest Service, Forest
      Inventory and Analysis program. The model-based population estimate of C stocks
      for CWD (i.e., pieces and slash piles) in the conterminous U.S. was 9 percent
      (145.1 Tg) greater than the field-based estimate. The relatively small absolute
      difference was driven by contrasting results for each CWD component. The model
      based population estimate of C stocks from CWD pieces was 17 percent (230.3 Tg)
      greater than the field-based estimate, while the model-based estimate of C stocks
      from CWD slash piles was 27 percent (85.2 Tg) smaller than the field-based
      estimate. In general, models overestimated the C density per-unit-area from slash
      piles early in stand development and underestimated the C density from CWD pieces
      in young stands. This resulted in significant differences in CWD C stocks by
      region and ownership. The disparity in estimates across spatial scales
      illustrates the complexity in estimating CWD C in a NGHGI. Based on the results
      of this study, it is suggested that the U.S. adopt field-based estimates of CWD C
      stocks as a component of its NGHGI to both reduce the uncertainty within the
      inventory and improve the sensitivity to potential management and climate change
      events.

PMID- 23544113
TI  - Nonsuicidal self-injury and suicidal behavior: a latent class analysis among
      young adults.
AB  - Although there is a general consensus among researchers that engagement in
      nonsuicidal self-injury (NSSI) is associated with increased risk for suicidal
      behavior, little attention has been given to whether suicidal risk varies among
      individuals engaging in NSSI. To identify individuals with a history of NSSI who
      are most at risk for suicidal behavior, we examined individual variability in
      both NSSI and suicidal behavior among a sample of young adults with a history of
      NSSI (N = 439, Mage = 19.1). Participants completed self-report measures
      assessing NSSI, suicidal behavior, and psychosocial adjustment (e.g., depressive
      symptoms, daily hassles). We conducted a latent class analysis using several
      characteristics of NSSI and suicidal behaviors as class indicators. Three
      subgroups of individuals were identified: 1) an infrequent NSSI/not high risk for
      suicidal behavior group, 2) a frequent NSSI/not high risk for suicidal behavior
      group, and 3) a frequent NSSI/high risk for suicidal behavior group. Follow-up
      analyses indicated that individuals in the 'frequent NSSI/high risk for suicidal
      behavior' group met the clinical-cut off score for high suicidal risk and
      reported significantly greater levels of suicidal ideation, attempts, and risk
      for future suicidal behavior as compared to the other two classes. Thus, this
      study is the first to identity variability in suicidal risk among individuals
      engaging in frequent and multiple methods of NSSI. Class 3 was also
      differentiated by higher levels of psychosocial impairment relative to the other
      two classes, as well as a comparison group of non-injuring young adults. Results
      underscore the importance of assessing individual differences in NSSI
      characteristics, as well as psychosocial impairment, when assessing risk for
      suicidal behavior.

PMID- 23544114
TI  - Spontaneous mutation reveals influence of exopolysaccharide on Lactobacillus
      johnsonii surface characteristics.
AB  - As a competitive exclusion agent, Lactobacillus johnsonii FI9785 has been shown
      to prevent the colonization of selected pathogenic bacteria from the chicken
      gastrointestinal tract. During growth of the bacterium a rare but consistent
      emergence of an altered phenotype was noted, generating smooth colonies in
      contrast to the wild type rough form. A smooth colony variant was isolated and
      two-dimensional gel analysis of both strains revealed a protein spot with
      different migration properties in the two phenotypes. The spot in both gels was
      identified as a putative tyrosine kinase (EpsC), associated with a predicted
      exopolysaccharide gene cluster. Sequencing of the epsC gene from the smooth
      mutant revealed a single substitution (G to A) in the coding strand, resulting in
      the amino acid change D88N in the corresponding gene product. A native plasmid of
      L. johnsonii was engineered to produce a novel vector for constitutive expression
      and this was used to demonstrate that expression of the wild type epsC gene in
      the smooth mutant produced a reversion to the rough colony phenotype. Both the
      mutant and epsC complemented strains had increased levels of exopolysaccharides
      compared to the wild type strain, indicating that the rough phenotype is not
      solely associated with the quantity of exopolysaccharide. Another gene in the
      cluster, epsE, that encoded a putative undecaprenyl-phosphate
      galactosephosphotransferase, was deleted in order to investigate its role in
      exopolysaccharide biosynthesis. The DeltaepsE strain exhibited a large increase
      in cell aggregation and a reduction in exopolysaccharide content, while plasmid
      complementation of epsE restored the wild type phenotype. Flow cytometry showed
      that the wild type and derivative strains exhibited clear differences in their
      adhesive ability to HT29 monolayers in tissue culture, demonstrating an impact of
      EPS on surface properties and bacteria-host interactions.

PMID- 23544115
TI  - Macaque monkeys can learn token values from human models through vicarious
      reward.
AB  - Monkeys can learn the symbolic meaning of tokens, and exchange them to get a
      reward. Monkeys can also learn the symbolic value of a token by observing
      conspecifics but it is not clear if they can learn passively by observing other
      actors, e.g., humans. To answer this question, we tested two monkeys in a token
      exchange paradigm in three experiments. Monkeys learned token values through
      observation of human models exchanging them. We used, after a phase of object
      familiarization, different sets of tokens. One token of each set was rewarded
      with a bit of apple. Other tokens had zero value (neutral tokens). Each token was
      presented only in one set. During the observation phase, monkeys watched the
      human model exchange tokens and watched them consume rewards (vicarious rewards).
      In the test phase, the monkeys were asked to exchange one of the tokens for food
      reward. Sets of three tokens were used in the first experiment and sets of two
      tokens were used in the second and third experiments. The valuable token was
      presented with different probabilities in the observation phase during the first
      and second experiments in which the monkeys exchanged the valuable token more
      frequently than any of the neutral tokens. The third experiments examined the
      effect of unequal probabilities. Our results support the view that monkeys can
      learn from non-conspecific actors through vicarious reward, even a symbolic task
      like the token-exchange task.

PMID- 23544116
TI  - Expression levels of obesity-related genes are associated with weight change in
      kidney transplant recipients.
AB  - BACKGROUND: The aim of this study was to investigate the association of gene
      expression profiles in subcutaneous adipose tissue with weight change in kidney
      transplant recipients and to gain insights into the underlying mechanisms of
      weight gain. METHODOLOGY/PRINCIPAL FINDINGS: A secondary data analysis was done
      on a subgroup (n = 26) of existing clinical and gene expression data from a
      larger prospective longitudinal study examining factors contributing to weight
      gain in transplant recipients. Measurements taken included adipose tissue gene
      expression profiles at time of transplant, baseline and six-month weight, and
      demographic data. Using multivariate linear regression analysis controlled for
      race and gender, expression levels of 1553 genes were significantly (p<0.05)
      associated with weight change. Functional analysis using Gene Ontology and Kyoto
      Encyclopedia of Genes and Genomes classifications identified metabolic pathways
      that were enriched in this dataset. Furthermore, GeneIndexer literature mining
      analysis identified a subset of genes that are highly associated with obesity in
      the literature and Ingenuity pathway analysis revealed several significant gene
      networks associated with metabolism and endocrine function. Polymorphisms in
      several of these genes have previously been linked to obesity.
      CONCLUSIONS/SIGNIFICANCE: We have successfully identified a set of molecular
      pathways that taken together may provide insights into the mechanisms of weight
      gain in kidney transplant recipients. Future work will be done to determine how
      these pathways may contribute to weight gain.

PMID- 23544117
TI  - Effectiveness of music education for the improvement of reading skills and
      academic achievement in young poor readers: a pragmatic cluster-randomized,
      controlled clinical trial.
AB  - INTRODUCTION: Difficulties in word-level reading skills are prevalent in
      Brazilian schools and may deter children from gaining the knowledge obtained
      through reading and academic achievement. Music education has emerged as a
      potential method to improve reading skills because due to a common
      neurobiological substratum. OBJECTIVE: To evaluate the effectiveness of music
      education for the improvement of reading skills and academic achievement among
      children (eight to 10 years of age) with reading difficulties. METHOD: 235
      children with reading difficulties in 10 schools participated in a five-month,
      randomized clinical trial in cluster (RCT) in an impoverished zone within the
      city of Sao Paulo to test the effects of music education intervention while
      assessing reading skills and academic achievement during the school year. Five
      schools were chosen randomly to incorporate music classes (n = 114), and five
      served as controls (n = 121). Two different methods of analysis were used to
      evaluate the effectiveness of the intervention: The standard method was intention
      to-treat (ITT), and the other was the Complier Average Causal Effect (CACE)
      estimation method, which took compliance status into account. RESULTS: The ITT
      analyses were not very promising; only one marginal effect existed for the rate
      of correct real words read per minute. Indeed, considering ITT, improvements were
      observed in the secondary outcomes (slope of Portuguese = 0.21 [p<0.001] and
      slope of math = 0.25 [p<0.001]). As for CACE estimation (i.e., complier children
      versus non-complier children), more promising effects were observed in terms of
      the rate of correct words read per minute [beta = 13.98, p<0.001] and
      phonological awareness [beta = 19.72, p<0.001] as well as secondary outcomes
      (academic achievement in Portuguese [beta = 0.77, p<0.0001] and math [beta =
      0.49, p<0.001] throughout the school year). CONCLUSION: The results may be seen
      as promising, but they are not, in themselves, enough to make music lessons as
      public policy.

PMID- 23544118
TI  - Conservation priorities for Prunus africana defined with the aid of spatial
      analysis of genetic data and climatic variables.
AB  - Conservation priorities for Prunus africana, a tree species found across
      Afromontane regions, which is of great commercial interest internationally and of
      local value for rural communities, were defined with the aid of spatial analyses
      applied to a set of georeferenced molecular marker data (chloroplast and nuclear
      microsatellites) from 32 populations in 9 African countries. Two approaches for
      the selection of priority populations for conservation were used, differing in
      the way they optimize representation of intra-specific diversity of P. africana
      across a minimum number of populations. The first method (S1) was aimed at
      maximizing genetic diversity of the conservation units and their distinctiveness
      with regard to climatic conditions, the second method (S2) at optimizing
      representativeness of the genetic diversity found throughout the species' range.
      Populations in East African countries (especially Kenya and Tanzania) were found
      to be of great conservation value, as suggested by previous findings. These
      populations are complemented by those in Madagascar and Cameroon. The combination
      of the two methods for prioritization led to the identification of a set of 6
      priority populations. The potential distribution of P. africana was then modeled
      based on a dataset of 1,500 georeferenced observations. This enabled an
      assessment of whether the priority populations identified are exposed to threats
      from agricultural expansion and climate change, and whether they are located
      within the boundaries of protected areas. The range of the species has been
      affected by past climate change and the modeled distribution of P. africana
      indicates that the species is likely to be negatively affected in future, with an
      expected decrease in distribution by 2050. Based on these insights, further
      research at the regional and national scale is recommended, in order to
      strengthen P. africana conservation efforts.

PMID- 23544119
TI  - Distribution dynamics of recombinant Lactobacillus in the gastrointestinal tract
      of neonatal rats.
AB  - One approach to deliver therapeutic agents, especially proteins, to the gastro
      intestinal (GI) tract is to use commensal bacteria as a carrier. Genus
      Lactobacillus is an attractive candidate for use in this approach. However, a
      system for expressing exogenous proteins at a high level has been lacking in
      Lactobacillus. Moreover, it will be necessary to introduce the recombinant
      Lactobacillus into the GI tract, ideally by oral administration. Whether orally
      administered Lactobacillus can reach and reside in the GI tract has not been
      explored in neonates. In this study, we have examined these issues in neonatal
      rats. To achieve a high level of protein expression in Lactobacillus, we tested
      the impact of three promoters and two backbones on protein expression levels
      using mRFP1, a red fluorescent protein, as a reporter. We found that a
      combination of an L-lactate dehydrogenase (ldhL) promoter of Lactobacillus sakei
      with a backbone from pLEM415 yielded the highest level of reporter expression.
      When this construct was used to transform Lactobacillus casei, Lactobacillus
      delbrueckii and Lactobacillus acidophilus, high levels of mRFP1 were detected in
      all these species and colonies of transformed Lactobacillus appeared pink under
      visible light. To test whether orally administered Lactobacillus can be retained
      in the GI tract of neonates, we fed the recombinant Lactobacillus casei to
      neonatal rats. We found that about 3% of the bacteria were retained in the GI
      tract of the rats at 24 h after oral feeding with more recombinant Lactobacillus
      in the stomach and small intestine than in the cecum and colon. No mortality was
      observed throughout this study with Lactobacillus. In contrast, all neonatal rats
      died within 24 hours after fed with transformed E. coli. Taken together, our
      results indicate that Lactobacillus has the potential to be used as a vehicle for
      the delivery of therapeutic agents to neonates.

PMID- 23544120
TI  - Chito-oligosaccharide inhibits the de-methylation of a 'CpG' island within the
      leptin (LEP) promoter during adipogenesis of 3T3-L1 cells.
AB  - Chito-oligosaccharide (COS) is a natural bioactive compound, which has been shown
      to suppress lipid metabolic genes and lipid accumulation in differentiating
      adipocytes. Leptin has been identified as a key regulator of energy homeostasis
      and is known to be under epigenetic regulation during adipogenesis. Hence, the
      first objective of this experiment was to compare leptin gene (LEP) expression
      and leptin secretion during the different stages of adipogenesis and to
      investigate the effect of COS on these processes. As COS inhibited LEP expression
      during adipogenesis, the second aim was to investigate the methylation dynamics
      of a 'CpG' island in the proximal region of the LEP promoter during adipogenesis
      and to determine the effect of COS on this process. Mouse 3T3-L1 cells were
      stimulated to differentiate in the absence or presence of COS and the levels of
      leptin mRNA and protein were evaluated on days 0, 2, 4 and 6 post-induction of
      differentiation (PID). The extent of de-methylation of six CpG sites was
      evaluated. LEP mRNA transcript and protein could not be detected on either day
      0PID or 2PID. In contrast, both were detected on day 4PID (P<0.05) and 6PID
      (P<0.001) and both were inhibited by COS (P<0.001). Of the six CpG sites
      analyzed, CpG_52, CpG_62 and CpG_95 became 11.5, 5.0 and 5.0% de-methylated
      between day 2PID and 6PID, respectively. COS blocked this de-methylation event at
      CpG_52 (P<0.001), CpG_62 (P<0.01) and CpG_95 (P<0.01) on day 6PID. These data
      suggest that COS can have an epigenetic effect on differentiating adipocytes, a
      novel biological function of COS which has potential applications for the
      manipulation of leptin gene expression, adipogenesis, and conditions within the
      metabolic syndrome spectrum.

PMID- 23544122
TI  - Influence of natural thermal gradients on whole animal rates of protein synthesis
      in marine gammarid amphipods.
AB  - Although temperature is known to have an important effect on protein synthesis
      rates and growth in aquatic ectotherms held in the laboratory, little is known
      about the effects of thermal gradients on natural populations in the field. To
      address this issue we determined whole-animal fractional rates of protein
      synthesis (ks ) in four dominant species of gammarid amphipods with different
      distributions along the coasts of Western Europe from arctic to temperate
      latitudes. Up to three populations of each species were collected in the summer
      and ks measured within 48 h. Summer ks values were relatively high in the
      temperate species, Gammarus locusta, from Portugal (48 degrees N) and Wales (53
      degrees N) and were maintained across latitudes by the conservation of
      translational efficiency. In sharp contrast, summer ks remained remarkably low in
      the boreal/temperate species G. duebeni from Wales, Scotland (58 degrees N) and
      Tromso (70 degrees N), probably as a temporary energy saving strategy to ensure
      survival in rapidly fluctuating environments of the high intertidal. Values for
      ks increased in acclimated G. duebeni from Scotland and Tromso showing a lack of
      compensation with latitude. In the subarctic/boreal species, G. oceanicus, summer
      ks remained unchanged in Scotland and Tromso but fell significantly in Svalbard
      (79 degrees N) at 5 degrees C, despite a slight increase in RNA content. At 79
      degrees N, mean ks was 4.5 times higher in the circumpolar species G. setosus
      than in G. oceanicus due to a doubling in RNA content. The relationship between
      whole-animal protein synthesis rates and natural thermal gradients is complex,
      varies between species and appears to be associated with local temperatures and
      their variability, as well as changes in other environmental factors.

PMID- 23544121
TI  - Genome sequencing unveils a novel sea enterotoxin-carrying PVL phage in
      Staphylococcus aureus ST772 from India.
AB  - Staphylococcus aureus is a major human pathogen, first recognized as a leading
      cause of hospital-acquired infections. Community-associated S. aureus (CA-SA)
      pose a greater threat due to increase in severity of infection and disease among
      children and healthy adults. CA-SA strains in India are genetically diverse,
      among which is the sequence type (ST) 772, which has now spread to Australia,
      Europe and Japan. Towards understanding the genetic characteristics of ST772, we
      obtained draft genome sequences of five relevant clinical isolates and studied
      the properties of their PVL-carrying prophages, whose presence is a defining
      hallmark of CA-SA. We show that this is a novel prophage, which carries the
      structural genes of the hlb-carrying prophage and includes the sea enterotoxin.
      This architecture probably emerged early within the ST772 lineage, at least in
      India. The sea gene, unique to ST772 PVL, despite having promoter sequence
      characteristics typical of low expression, appears to be highly expressed during
      early phase of growth in laboratory conditions. We speculate that this might be a
      consequence of its novel sequence context. The crippled nature of the hlb
      converting prophage in ST772 suggests that widespread mobility of the sea
      enterotoxin might be a selective force behind its 'transfer' to the PVL prophage.
      Wild type ST772 strains induced strong proliferative responses as well as high
      cytotoxic activity against neutrophils, likely mediated by superantigen SEA and
      the PVL toxin respectively. Both proliferation and cytotoxicity were markedly
      reduced in a cured ST772 strain indicating the impact of the phage on virulence.
      The presence of SEA alongside the genes for the immune system-modulating PVL
      toxin may contribute to the success and virulence of ST772.

PMID- 23544123
TI  - Rapid and recent world-wide diversification of bluegrasses (Poa, Poaceae) and
      related genera.
AB  - Rapid species diversifications provide fascinating insight into the development
      of biodiversity in time and space. Most biological radiations studied to date,
      for example that of cichlid fishes or Andean lupines, are confined to isolated
      geographical areas like lakes, islands or island-like regions. Using DNA sequence
      data of the ribosomal internal transcribed spacer (ITS) for many species of the
      Poa alliance, a group comprising about 775 C3 grass species, revealed rapid and
      parallel diversifications in various parts of the world. Some of these radiations
      are restricted to isolated areas like the Andes, whereas others are typical of
      the lowlands of mainly the northern hemisphere. These radiations thus are not
      restricted to island-like areas and are seemingly actively ongoing. The ages of
      the diversifying clades are estimated to be 2.5-0.23 million years (Myr).
      Conservative diversification rates in the Poa alliance amount to 0.89-3.14
      species per Myr, thus are in the order of, or even exceeding, other instances of
      well-known radiations. The grass radiations of the mainly cold-adapted Poa
      alliance coincide with the Late Tertiary global cooling, which resulted in the
      retreat of forests and the subsequent formation of cold-adapted grasslands
      especially in the northern, but also in parts of the southern hemisphere. The
      cold tolerance, suggested to be one of the ecological key innovations, may have
      been acquired during the early diversification of the subfamily Pooideae, but
      became significant millions of years later during the Pliocene/Pleistocene
      radiation of the Poa alliance.

PMID- 23544124
TI  - Wengen, the sole tumour necrosis factor receptor in Drosophila, collaborates with
      moesin to control photoreceptor axon targeting during development.
AB  - Photoreceptor neurons (R cells) in the Drosophila eye define a map of visual
      space by connecting to targets in distinct layers of the optic lobe, with R1-6
      cells connecting to the lamina (the first optic ganglion) and R7 and R8 cells
      connecting to the medulla (the second optic ganglion). Here, we show that Wengen
      (Wgn) directly binds Moesin (Moe) through a cytosolic membrane proximal domain
      and this interaction is important for mediating two distinct aspects of axonal
      targeting. First, we show that loss of wgn or moe function disrupts cell
      autonomous R8 axon targeting. Second, we report that wgn or moe mutants show
      defects in R2-R5 targeting that result from disruption of non-cell autonomous
      effects, which are secondary to the cell autonomous R8 phenotype. Thus, these
      studies reveal that the Wgn-Moe signaling cascade plays a key role in
      photoreceptor target field innervations through cell autonomous and non-cell
      autonomous mechanisms.

PMID- 23544125
TI  - Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates
      circulating PCSK9 levels.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted
      inhibitor of the low-density lipoprotein (LDL) receptor and an important
      regulator of LDL metabolism. Elevated PCSK9 levels have been associated with
      cardiovascular risk. The purpose of this study was to investigate how ezetimibe
      and simvastatin, alone and in combination, affect PCSK9 circulating
      concentrations. METHODS: A single center, randomized, open-label parallel 3-group
      study in healthy men (mean age 32+/-9 years, body mass index 25.7+/-3.2 kg/m(2))
      was performed. Each group of 24 subjects was treated for 14 days with either
      simvastatin 40 mg/d, ezetimibe 10 mg/d, or with both drugs. Multivariate analysis
      was used to investigate parameters influencing the change in PCSK9 concentrations
      under treatment. RESULTS: The baseline plasma PCSK9 concentrations in the total
      cohort were 52+/-20 ng/mL with no statistically significant differences between
      the groups. They were increased by 68+/-85% by simvastatin (P = 0.0014), by 10+/
      38% by ezetimibe (P = 0.51) and by 67+/-91% by simvastatin plus ezetimibe (P =
      0.0013). The increase in PCSK9 was inversely correlated with baseline PCSK9
      concentrations (Spearman's R = -0.47, P<0.0001) and with the percent change in
      LDL cholesterol concentrations (Spearman's R = -0.30, P<0.01). In multivariate
      analyses, only baseline PCSK9 concentrations (beta = -1.68, t = -4.04, P<0.0001),
      percent change in LDL cholesterol from baseline (beta = 1.94, t = 2.52, P =
      0.014), and treatment with simvastatin (P = 0.016), but not ezetimibe (P = 0.42),
      significantly influenced changes in PCSK9 levels. Parameters without effect on
      PCSK9 concentration changes were age, body mass index, body composition, thyroid
      function, kidney function, glucose metabolism parameters, adipokines, markers of
      cholesterol synthesis and absorption, and molecular markers of cholesterol
      metabolism. CONCLUSIONS: Ezetimibe does not increase circulating PCSK9
      concentrations while simvastatin does. When added to simvastatin, ezetimibe does
      not cause an incremental increase in PCSK9 concentrations. Changes in PCSK9
      concentrations are tightly regulated and mainly influenced by baseline PCSK9
      levels and changes in LDL cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00317993.

PMID- 23544126
TI  - Bt crops producing Cry1Ac, Cry2Ab and Cry1F do not harm the green lacewing,
      Chrysoperla rufilabris.
AB  - The biological control function provided by natural enemies is regarded as a
      protection goal that should not be harmed by the application of any new pest
      management tool. Plants producing Cry proteins from the bacterium, Bacillus
      thuringiensis (Bt), have become a major tactic for controlling pest Lepidoptera
      on cotton and maize and risk assessment studies are needed to ensure they do not
      harm important natural enemies. However, using Cry protein susceptible hosts as
      prey often compromises such studies. To avoid this problem we utilized pest
      Lepidoptera, cabbage looper (Trichoplusia ni) and fall armyworm (Spodoptera
      frugiperda), that were resistant to Cry1Ac produced in Bt broccoli (T. ni),
      Cry1Ac/Cry2Ab produced in Bt cotton (T. ni), and Cry1F produced in Bt maize (S.
      frugiperda). Larvae of these species were fed Bt plants or non-Bt plants and then
      exposed to predaceous larvae of the green lacewing Chrysoperla rufilabris.
      Fitness parameters (larval survival, development time, fecundity and egg hatch)
      of C. rufilabris were assessed over two generations. There were no differences in
      any of the fitness parameters regardless if C. rufilabris consumed prey (T. ni or
      S. frugiperda) that had consumed Bt or non-Bt plants. Additional studies
      confirmed that the prey contained bioactive Cry proteins when they were consumed
      by the predator. These studies confirm that Cry1Ac, Cry2Ab and Cry1F do not pose
      a hazard to the important predator C. rufilabris. This study also demonstrates
      the power of using resistant hosts when assessing the risk of genetically
      modified plants on non-target organisms.

PMID- 23544127
TI  - Identification of multiple novel protein biomarkers shed by human serous ovarian
      tumors into the blood of immunocompromised mice and verified in patient sera.
AB  - The most cancer-specific biomarkers in blood are likely to be proteins shed
      directly by the tumor rather than less specific inflammatory or other host
      responses. The use of xenograft mouse models together with in-depth proteome
      analysis for identification of human proteins in the mouse blood is an under
      utilized strategy that can clearly identify proteins shed by the tumor. In the
      current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous
      tumors were identified based upon human vs. mouse species differences using a
      four-dimensional plasma proteome fractionation strategy. A multi-step
      prioritization and verification strategy was subsequently developed to
      efficiently select some of the most promising biomarkers from this large number
      of candidates. A key step was parallel analysis of human proteins detected in the
      tumor supernatant, because substantially greater sequence coverage for many of
      the human proteins initially detected in the xenograft mouse plasma confirmed
      assignments as tumor-derived human proteins. Verification of candidate biomarkers
      in patient sera was facilitated by in-depth, label-free quantitative comparisons
      of serum pools from patients with ovarian cancer and benign ovarian tumors. The
      only proteins that advanced to multiple reaction monitoring (MRM) assay
      development were those that exhibited increases in ovarian cancer patients
      compared with benign tumor controls. MRM assays were facilely developed for all
      11 novel biomarker candidates selected by this process and analysis of larger
      pools of patient sera suggested that all 11 proteins are promising candidate
      biomarkers that should be further evaluated on individual patient blood samples.

PMID- 23544128
TI  - Predictive value of the tuberculin skin test among newly arriving immigrants.
AB  - RATIONALE: Screening and treating newly arriving immigrants for latent
      tuberculosis infection (LTBI) in low-incidence countries could be promising to
      reduce the tuberculosis incidence among this population. The effectiveness of
      screening with the tuberculin skin test (TST) is unknown. OBJECTIVES: To estimate
      the risk of progression to tuberculosis within two years after entry, stratified
      by TST result at entry. METHODS: In a case-base design, we determined the
      prevalence of TST positives (10 mm and 15 mm) among a representative cohort of
      immunocompetent immigrants (n = 643) aged >=18 years who arrived between April
      2009 and March 2011 in The Netherlands (base cohort). Immigrants who progressed
      to tuberculosis within two years after arrival in 2005, 2006 or 2007 were
      extracted from the Netherlands Tuberculosis Register (case source cohort). The
      prevalence of TST positives from the base cohort was projected on the case source
      cohort to estimate the risk of progression to active tuberculosis by using
      bayesian analyses to adjust for the sensitivity of the TST and Poisson regression
      analyses to take into account the random error of the number of extracted cases.
      RESULTS: The prevalence of TST positives was 42% and 23% for a cut-off value of
      10 mm and 15 mm, respectively. The overall risk of progression to tuberculosis if
      TST positive was 238 per 100,000 population (95% CI 151-343) and 295 per 100,000
      population (95% CI 161-473) for a cut-off value of >=10 mm and >=15 mm,
      respectively. The corresponding risk for TST negatives was 19 (95% CI 0-59) and
      58 (95% CI 25-103). CONCLUSION: The TST has the discriminatory ability to
      differentiate between individuals at low and high risk of disease.

PMID- 23544129
TI  - Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis
      independent neuronal cell death.
AB  - The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by
      PIKfyve, regulates a number of intracellular membrane trafficking pathways.
      Genetic alteration of the PIKfyve complex, leading to even a mild reduction in
      PtdIns(3,5)P 2, results in marked neurodegeneration via an uncharacterised
      mechanism. In the present study we have shown that selectively inhibiting PIKfyve
      activity, using YM-201636, significantly reduces the survival of primary mouse
      hippocampal neurons in culture. YM-201636 treatment promoted vacuolation of
      endolysosomal membranes followed by apoptosis-independent cell death. Many
      vacuoles contained intravacuolar membranes and inclusions reminiscent of
      autolysosomes. Accordingly, YM-201636 treatment increased the level of the
      autophagosomal marker protein LC3-II, an effect that was potentiated by
      inhibition of lysosomal proteases, suggesting that alterations in autophagy could
      be a contributing factor to neuronal cell death.

PMID- 23544130
TI  - The tumor-suppressive miR-497-195 cluster targets multiple cell-cycle regulators
      in hepatocellular carcinoma.
AB  - MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and
      commonly deregulated in carcinogenesis. To explore functionally crucial tumor
      suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed
      integrative function- and expression-based screenings of TS-miRNAs in six HCC
      cell lines. The screenings identified seven miRNAs, which showed growth
      suppressive activities through the overexpression of each miRNA and were
      endogenously downregulated in HCC cell lines. Further expression analyses using a
      large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR
      101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs.
      Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth
      suppressive activity with induction of G1 arrest. Comprehensive exploration of
      their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq)
      and genome-wide expression profiling after their overexpression followed by
      pathway analysis, revealed a significant enrichment of cell cycle regulators.
      Among the candidates, we successfully identified CCNE1, CDC25A, CCND3, CDK4, and
      BTRC as direct targets for miR-497 and miR-195. Moreover, target genes frequently
      upregulated in HCC in a tumor-specific manner, such as CDK6, CCNE1, CDC25A and
      CDK4, showed an inverse correlation in the expression of miR-195 and miR-497, and
      their targets. These results suggest the molecular pathway regulating cell cycle
      progression to be integrally altered by downregulation of miR-195 and miR-497
      expression, leading to the aberrant cell proliferation in hepatocarcinogenesis.

PMID- 23544131
TI  - Single-cell measurements of IgE-mediated FcepsilonRI signaling using an
      integrated microfluidic platform.
AB  - Heterogeneity in responses of cells to a stimulus, such as a pathogen or
      allergen, can potentially play an important role in deciding the fate of the
      responding cell population and the overall systemic response. Measuring
      heterogeneous responses requires tools capable of interrogating individual cells.
      Cell signaling studies commonly do not have single-cell resolution because of the
      limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and
      DNA microarrays. Microfluidics devices are increasingly being used to overcome
      these limitations. Here, we report on a microfluidic platform for cell signaling
      analysis that combines two orthogonal single-cell measurement technologies: on
      chip flow cytometry and optical imaging. The device seamlessly integrates cell
      culture, stimulation, and preparation with downstream measurements permitting
      hands-free, automated analysis to minimize experimental variability. The platform
      was used to interrogate IgE receptor (FcepsilonRI) signaling, which is
      responsible for triggering allergic reactions, in RBL-2H3 cells. Following on
      chip crosslinking of IgE-FcepsilonRI complexes by multivalent antigen, we
      monitored signaling events including protein phosphorylation, calcium
      mobilization and the release of inflammatory mediators. The results demonstrate
      the ability of our platform to produce quantitative measurements on a cell-by
      cell basis from just a few hundred cells. Model-based analysis of the Syk
      phosphorylation data suggests that heterogeneity in Syk phosphorylation can be
      attributed to protein copy number variations, with the level of Syk
      phosphorylation being particularly sensitive to the copy number of Lyn.

PMID- 23544132
TI  - Wilm's tumor-1 protein levels in urinary exosomes from diabetic patients with or
      without proteinuria.
AB  - BACKGROUND: Podocyte injury is an early feature of diabetic nephropathy (DN).
      Recently, urinary exosomal Wilm's tumor-1 protein (WT1), shed by renal epithelial
      cells, has been proposed as a novel biomarker for podocyte injury. However, its
      usefulness as biomarker for early diabetic nephropathy has not been verified yet.
      We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its
      role as a non-invasive biomarker for predicting early renal function decline.
      METHODS: The expression of WT1 protein in urinary exosomes from spot urine
      samples of type-1 diabetes mellitus patients (n = 48) and healthy controls (n =
      25) were analyzed. Patients were divided based on their urinary albumin
      excretion, ACR (mg/g creatinine) into non- proteinuria group (ACR<30 mg/g, n =
      30) and proteinuria group (ACR>30 mg/g, n = 18). Regression analysis was used to
      assess the association between urinary exosomal levels of WT1 with parameters for
      renal function. Receiver Operating Characteristic (ROC) curve analysis was used
      to determine the diagnostic performance of exosomal WT-1. RESULTS: WT1 protein
      was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The
      levels of urinary exosomal WT1 protein is significantly higher (p = 0.001) in
      patients with proteinuria than in those without proteinuria. In addition, all the
      patients with proteinuria but only half of the patients without proteinuria were
      positive for exosomal WT1. We found that the level of exosomal WT1 were
      associated with a significant increase in urine protein-to-creatinine ratio,
      albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR.
      Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased
      renal function compared to WT1-negative patients. ROC analysis shows that WT-1
      effectively predict GFR<60 ml. min-1/1.73 m(2). CONCLUSION: The predominant
      presence of WT1 protein in urinary exosomes of diabetic patients and increase in
      its expression level with decline in renal function suggest that it could be
      useful as early non-invasive marker for diabetic nephropathy.

PMID- 23544133
TI  - Effective part-task training as evidence of distinct adaptive processes with
      different time scales.
AB  - For some types of visuo-motor transformations like large visuo-motor rotations or
      the complex transformation of a sliding first-order lever, distinct adaptive
      processes have been hypothesized that produce a rapid, discrete approximation of
      the transformation and a slow, graded fine tuning, respectively. Here we
      investigate whether part-task training of only the second of these processes,
      namely the fine tuning, transfers to the subsequent performance in a condition
      with the full transformation of the sliding first-order lever. Therefore, we
      compared performance of three groups with different practice conditions during
      transfer to the full transformation. While two groups only practiced the fine
      tuning without the right-left inversion of the lever prior to transfer, a third
      group practiced the full lever transformation. Our results show a positive, but
      less than perfect transfer of the isolated practice of the fine tuning on
      performance with the full transformation. For the fine tuning itself, transfer
      was not reliably different from being perfect. The observation that the fine
      tuning can be acquired separately and added to the later adaptation to the left
      right inversion of the lever supports the notion that these slow and fast
      processes progress rather independently. The additional finding that the
      preceding acquisition of the fine tuning also facilitates the subsequent rapid
      process could be due to generalized learning-to-learn or to a more precise
      assignment of movement errors to the process from which they originate.

PMID- 23544135
TI  - Exposure to the proton scavenger glycine under alkaline conditions induces
      Escherichia coli viability loss.
AB  - Our previous work described a clear loss of Escherichia coli (E. coli) membrane
      integrity after incubation with glycine or its N-methylated derivatives N
      methylglycine (sarcosine) and N,N-dimethylglycine (DMG), but not N,N,N
      trimethylglycine (betaine), under alkaline stress conditions. The current study
      offers a thorough viability analysis, based on a combination of real-time
      physiological techniques, of E. coli exposed to glycine and its N-methylated
      derivatives at alkaline pH. Flow cytometry was applied to assess various
      physiological parameters such as membrane permeability, esterase activity,
      respiratory activity and membrane potential. ATP and inorganic phosphate
      concentrations were also determined. Membrane damage was confirmed through the
      measurement of nucleic acid leakage. Results further showed no loss of esterase
      or respiratory activity, while an instant and significant decrease in the ATP
      concentration occurred upon exposure to either glycine, sarcosine or DMG, but not
      betaine. There was a clear membrane hyperpolarization as well as a significant
      increase in cellular inorganic phosphate concentration. Based on these results,
      we suggest that the inability to sustain an adequate level of ATP combined with a
      decrease in membrane functionality leads to the loss of bacterial viability when
      exposed to the proton scavengers glycine, sarcosine and DMG at alkaline pH.

PMID- 23544134
TI  - Mental rotation: effects of gender, training and sleep consolidation.
AB  - A wide range of experimental studies have provided evidence that a night of sleep
      contributes to memory consolidation. Mental rotation (MR) skill is characterized
      by fundamental aspect of both cognitive and motor abilities which can be improved
      within practice sessions, but little is known about the effect of consolidation
      after MR practice. In the present study, we investigated the effect of MR
      training and the following corresponding day- and sleep-related time
      consolidations in taking into account the well-established gender difference in
      MR. Forty participants (20 women) practiced a computerized version of the
      Vandenberg and Kuse MR task. Performance was evaluated before MR training, as
      well as prior to, and after a night of sleep or a similar daytime interval. Data
      showed that while men outperformed women during the pre-training test, brief MR
      practice was sufficient for women to achieve equivalent performance. Only
      participants subjected to a night of sleep were found to enhance MR performance
      during the retest, independently of gender. These results provide first evidence
      that a night of sleep facilitates MR performance compared with spending a similar
      daytime interval, regardless gender of the participants. Since MR is known to
      involve motor processes, the present data might contribute to schedule relevant
      mental practice interventions for fruitful applications in rehabilitation and
      motor learning processes.

PMID- 23544136
TI  - Flycatchers copy conspecifics in nest-site selection but neither personal
      experience nor frequency of tutors have an effect.
AB  - Using the behavior of others in guiding one's own behavior is a common strategy
      in animals. The prevailing theory predicts that young age and the inexperience of
      an individual are expected to increase the probability of adopting the behaviors
      of others. Also, the most common behavior in the population should be copied.
      Here, we tested the above predictions by examining social information use in the
      selection of nest-site features with a field experiment using a wild cavity
      nesting bird, the collared flycatcher (Ficedula albicollis). We used an
      experimental design in which geometric symbols depict nest-site features. By
      manipulating the apparent symbol choices of early settled individuals and
      monitoring the choices of later arriving birds, we can study social information
      use without bias from learned or innate preferences. Flycatchers were found to
      use social information in the selection of nest-site features, with about 60% of
      the population preferring the manipulated conspecific choices. However, age and
      experience as explanatory factors suggested by the social information use theory
      did not explain the choices. The present result, in concert with earlier similar
      experiments, implies that flycatchers may in some situations rely more on
      interspecific information in the selection of nest-site characteristics.

PMID- 23544137
TI  - The dynamic right-to-left translocation of Cerl2 is involved in the regulation
      and termination of Nodal activity in the mouse node.
AB  - The determination of left-right body asymmetry in mouse embryos depends on the
      interplay of molecules in a highly sensitive structure, the node. Here, we show
      that the localization of Cerl2 protein does not correlate to its mRNA expression
      pattern, from 3-somite stage onwards. Instead, Cerl2 protein displays a nodal
      flow-dependent dynamic behavior that controls the activity of Nodal in the node,
      and the transmission of the laterality information to the left lateral plate
      mesoderm (LPM). Our results indicate that Cerl2 initially localizes and prevents
      the activation of Nodal genetic circuitry on the right side of the embryo, and
      later its right-to-left translocation shutdowns Nodal activity in the node. The
      consequent prolonged Nodal activity in the node by the absence of Cerl2 affects
      local Nodal expression and prolongs its expression in the LPM. Simultaneous
      genetic removal of both Nodal node inhibitors, Cerl2 and Lefty1, sustains even
      longer and bilateral this LPM expression.

PMID- 23544138
TI  - Molecular determinants of mouse neurovirulence and mosquito infection for Western
      equine encephalitis virus.
AB  - Western equine encephalitis virus (WEEV) is a naturally occurring recombinant
      virus derived from ancestral Sindbis and Eastern equine encephalitis viruses. We
      previously showed that infection by WEEV isolates McMillan (McM) and IMP-181
      (IMP) results in high (~90-100%) and low (0%) mortality, respectively, in outbred
      CD-1 mice when virus is delivered by either subcutaneous or aerosol routes.
      However, relatively little is known about specific virulence determinants of
      WEEV. We previously observed that IMP infected Culex tarsalis mosquitoes at a
      high rate (app. 80%) following ingestion of an infected bloodmeal but these
      mosquitoes were infected by McM at a much lower rate (10%). To understand the
      viral role in these phenotypic differences, we characterized the pathogenic
      phenotypes of McM/IMP chimeras. Chimeras encoding the E2 of McM on an IMP
      backbone (or the reciprocal) had the most significant effect on infection
      phenotypes in mice or mosquitoes. Furthermore, exchanging the arginine, present
      on IMP E2 glycoprotein at position 214, for the glutamine present at the same
      position on McM, ablated mouse mortality. Curiously, the reciprocal exchange did
      not confer mouse virulence to the IMP virus. Mosquito infectivity was also
      determined and significantly, one of the important loci was the same as the mouse
      virulence determinant identified above. Replacing either IMP E2 amino acid 181 or
      214 with the corresponding McM amino acid lowered mosquito infection rates to McM
      like levels. As with the mouse neurovirulence, reciprocal exchange of amino acids
      did not confer mosquito infectivity. The identification of WEEV E2 amino acid 214
      as necessary for both IMP mosquito infectivity and McM mouse virulence indicates
      that they are mutually exclusive phenotypes and suggests an explanation for the
      lack of human or equine WEE cases even in the presence of active transmission.

PMID- 23544139
TI  - Depressive symptoms in Crohn's disease: relationship with immune activation and
      tryptophan availability.
AB  - Crohn's disease (CD) is associated with immune activation and depressive
      symptoms. This study determines the impact of anti-tumor necrosis factor (TNF)
      alpha treatment in CD patients on depressive symptoms and the degree to which
      tryptophan (TRP) availability and immune markers mediate this effect. Fifteen
      patients with CD, eligible for anti-TNF-alpha treatment were recruited. Disease
      activity (Harvey-Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI)),
      fatigue (Multidimensional Fatigue Inventory (MFI)), quality of life (Inflammatory
      Bowel Disease Questionnaire (IBDQ)), symptoms of depression and anxiety (Symptom
      Checklist (SCL-90), Beck Depression Inventory (BDI), Hamilton Depression Rating
      Scale (HDRS)), immune activation (acute phase proteins (APP)), zinc and TRP
      availability were assessed before treatment and after 2, 4 and 8 weeks. Anti-TNF
      alpha increased IBDQ scores and reduced all depression scores; however only SCL
      90 depression scores remained decreased after correction for HBI. Positive APPs
      decreased, while negative APPs increased after treatment. After correction for
      HBI, both level and percentage of gamma fraction were associated with SCL-90
      depression scores over time. After correction for HBI, patients with current/past
      depressive disorder displayed higher levels of positive APPs and lower levels of
      negative APPs and zinc. TRP availability remained invariant over time and there
      was no association between SCL-90 depression scores and TRP availability.
      Inflammatory reactions in CD are more evident in patients with comorbid
      depression, regardless of disease activity. Anti-TNF-alpha treatment in CD
      reduces depressive symptoms, in part independently of disease activity; there was
      no evidence that this effect was mediated by immune-induced changes in TRP
      availability.

PMID- 23544140
TI  - Nitrogen addition and warming independently influence the belowground micro-food
      web in a temperate steppe.
AB  - Climate warming and atmospheric nitrogen (N) deposition are known to influence
      ecosystem structure and functioning. However, our understanding of the
      interactive effect of these global changes on ecosystem functioning is relatively
      limited, especially when it concerns the responses of soils and soil organisms.
      We conducted a field experiment to study the interactive effects of warming and N
      addition on soil food web. The experiment was established in 2006 in a temperate
      steppe in northern China. After three to four years (2009-2010), we found that N
      addition positively affected microbial biomass and negatively influenced trophic
      group and ecological indices of soil nematodes. However, the warming effects were
      less obvious, only fungal PLFA showed a decreasing trend under warming.
      Interestingly, the influence of N addition did not depend on warming. Structural
      equation modeling analysis suggested that the direct pathway between N addition
      and soil food web components were more important than the indirect connections
      through alterations in soil abiotic characters or plant growth. Nitrogen
      enrichment also affected the soil nematode community indirectly through changes
      in soil pH and PLFA. We conclude that experimental warming influenced soil food
      web components of the temperate steppe less than N addition, and there was little
      influence of warming on N addition effects under these experimental conditions.

PMID- 23544141
TI  - Filtering across spatial scales: phylogeny, biogeography and community structure
      in bumble bees.
AB  - Despite the expansion of phylogenetic community analysis to understand community
      assembly, few studies have used these methods on mobile organisms and it has been
      suggested the local scales that are typically considered may be too small to
      represent the community as perceived by organisms with high mobility. Mobility is
      believed to allow species to mediate competitive interactions quickly and thus
      highly mobile species may appear randomly assembled in local communities. At
      larger scales, however, biogeographical processes could cause communities to be
      either phylogenetically clustered or even. Using phylogenetic community analysis
      we examined patterns of relatedness and trait similarity in communities of bumble
      bees (Bombus) across spatial scales comparing: local communities to regional
      pools, regional communities to continental pools and the continental community to
      a global species pool. Species composition and data on tongue lengths, a key
      foraging trait, were used to test patterns of relatedness and trait similarity
      across scales. Although expected to exhibit limiting similarity, local
      communities were clustered both phenotypically and phylogenetically. Larger
      spatial scales were also found to have more phylogenetic clustering but less
      trait clustering. While patterns of relatedness in mobile species have previously
      been suggested to exhibit less structure in local communities and to be less
      clustered than immobile species, we suggest that mobility may actually allow
      communities to have more similar species that can simply limit direct competition
      through mobility.

PMID- 23544142
TI  - Is active management the key to the conservation of saproxylic biodiversity?
      Pollarding promotes the formation of tree hollows.
AB  - Trees with hollows are key features sustaining biodiversity in wooded landscapes.
      They host rich assemblages of often highly specialised organisms. Hollow trees,
      however, have become rare and localised in Europe. Many of the associated biota
      is thus declining or endangered. The challenge of its conservation, therefore, is
      to safeguard the presence of hollow trees in sufficient numbers. Populations of
      numerous species associated with tree hollows and dead wood are often found in
      habitats that were formed by formerly common traditional silvicultural practices
      such as coppicing, pollarding or pasture. Although it has been occasionally
      mentioned that such practices increase the formation of hollows and the
      availability of often sun-exposed dead wood, their effect has never been
      quantified. Our study examined the hollow incidence in pollard and non-pollard
      (unmanaged) willows and the effect of pollarding on incremental growth rate by
      tree ring analysis. The probability of hollow occurrence was substantially higher
      in pollard than in non-pollard trees. Young pollards, especially, form hollows
      much more often than non-pollards; for instance, in trees of 50 cm DBH, the
      probability of hollow ocurrence was ~0.75 in pollards, but only ~0.3 in non
      pollards. No difference in growth rate was found. Pollarding thus leads to the
      rapid formation of tree hollows, a habitat usually associated with old trees. It
      is therefore potentially a very important tool in the restoration of saproxylic
      habitats and conservation of hollow-dependent fauna. If applied along e.g. roads
      and watercourses, pollarding could also be used to increase landscape
      connectivity for saproxylic organisms. In reserves where pollarding was formerly
      practiced, its restoration would be necessary to prevent loss of saproxylic
      biodiversity. Our results point to the importance of active management measures
      for maintaining availability, and spatial and temporal continuity of deadwood
      microhabitats.

PMID- 23544143
TI  - Endothelial NO synthase gene polymorphisms and risk of ischemic stroke in Asian
      population: a meta-analysis.
AB  - BACKGROUND: The association between polymorphism 4b/a, T-786C and G894T in
      endothelial NO synthase gene (eNOS) and ischemic stroke (IS) remains
      controversial in Asian. A meta-analysis was performed to better clarify the
      association between eNOS gene and IS risk. METHODS: Based on the search of
      PubMed, Web of Science (ISI), CNKI (National Knowledge Infrastructure), Wan Fang
      Med Online and CBM (Chinese Biology Medical Literature Database) databases, all
      eligible case-control or cohort studies were identified. Pooled odds ratios (ORs)
      with 95% confidence intervals (CIs) from fixed and random effect models were
      calculated. Heterogeneity among studies was evaluated using the I(2). Meta
      regression was used to explore the potential sources of between-study
      heterogeneity. Begg's test was used to estimate publication bias. RESULTS: Our
      study included 27 articles, contained 28 independent case-control studies,
      involved a total of 3,742 cases and 3,691 controls about 4b/a, 1,800 cases and
      1,751 controls about T-786C and 2,747 cases and 2,872 controls about G894T. A
      significant association of 4a allele with increased risk of IS was found in
      dominant (FEM: OR = 1.498, 95% CI = 1.329-1.689), recessive (FEM: OR = 2.132, 95%
      CI = 1.383-3.286) and codominant (REM: OR = 1.456, 95% CI = 1.235-1.716) models.
      For T-786C and G894T, there were significant associations with dominant and
      codominant genetic models, but not with recessive genetic model. CONCLUSIONS: The
      meta-analysis indicated that eNOS gene 4b/a, T-786C, G894T polymorphism might be
      associated with IS.

PMID- 23544144
TI  - The tyrosine kinase Btk regulates the macrophage response to Listeria
      monocytogenes infection.
AB  - In this study we investigated the role of Bruton's tyrosine kinase (Btk) in the
      immune response to the Gram-positive intracellular bacterium Listeria
      monocytogenes (Lm). In response to Lm infection, Btk was activated in bone marrow
      derived macrophages (BMMs) and Btk (-/-) BMMs showed enhanced TNF-alpha, IL-6 and
      IL-12p40 secretion, while type I interferons were produced at levels similar to
      wild-type (wt) BMMs. Although Btk-deficient BMMs displayed reduced phagocytosis
      of E. coli fragments, there was no difference between wt and Btk (-/-) BMMs in
      the uptake of Lm upon infection. Moreover, there was no difference in the
      response to heat-killed Lm between wt and Btk (-/-) BMMs, suggesting a role for
      Btk in signaling pathways that are induced by intracellular Lm. Finally, Btk (-/
      ) mice displayed enhanced resistance and an increased mean survival time upon Lm
      infection in comparison to wt mice. This correlated with elevated IFN-gamma and
      IL-12p70 serum levels in Btk (-/-) mice at day 1 after infection. Taken together,
      our data suggest an important regulatory role for Btk in macrophages during Lm
      infection.

PMID- 23544145
TI  - Influence of T-2 and HT-2 toxin on the blood-brain barrier in vitro: new
      experimental hints for neurotoxic effects.
AB  - The trichothecene mycotoxin T-2 toxin is a common contaminant of food and feed
      and is also present in processed cereal derived products. Cytotoxic effects of T
      2 toxin and its main metabolite HT-2 toxin are already well described with
      apoptosis being a major mechanism of action. However, effects on the central
      nervous system were until now only reported rarely. In this study we investigated
      the effects of T-2 and HT-2 toxin on the blood-brain barrier (BBB) in vitro.
      Besides strong cytotoxic effects on the BBB as determined by the CCK-8 assay,
      impairment of the barrier function starting at low nanomolar concentrations were
      observed for T-2 toxin. HT-2 toxin, however, caused barrier disruption at higher
      concentrations compared to T-2 toxin. Further, the influence on the tight
      junction protein occludin was studied and permeability of both toxins across the
      BBB was detected when applied from the apical (blood) or the basolateral (brain)
      side respectively. These results clearly indicate the ability of both toxins to
      enter the brain via the BBB.

PMID- 23544146
TI  - Decrease in blood pressure and regression of cardiovascular complications by
      angiotensin II vaccine in mice.
AB  - Vaccines have been recently developed to treat various diseases such as cancer,
      rheumatoid arthritis and Alzheimer's disease in addition to infectious diseases.
      However, before use in the clinical setting, vaccines targeting self-antigens
      must be demonstrated to be effective and safe, evoking an adequate humoral immune
      response from B cells while avoiding T cell activation in response to self.
      Although the vaccine targeting angiotensin II (Ang II) is efficient in rodents
      and humans, little is known regarding the immunological activation and safety of
      the vaccine. In this study, we evaluated the efficiency and safety of an Ang II
      peptide vaccine in mice. Immunization with Ang II conjugated to keyhole limpet
      hemocyanin (KLH) successfully induced the production of anti-Ang II antibody,
      which blocked Ang II signaling in human aortic smooth muscle cells. However, Ang
      II itself did not activate T cells, as assessed by the proliferation and
      lymphokine production of T cells in immunized mice, whereas KLH activated T
      cells. In an Ang II-infused model, the non-immunized mice showed high blood
      pressure (BP), whereas the immunized mice (Ang II-KLH) showed a significant
      decrease in systolic BP, accompanied by significant reductions in cardiac
      hypertrophy and fibrosis. Importantly, anti-Ang II antibody titer was not
      elevated even after the administration of large amounts of Ang II, indicating
      that Ang II itself boosted antibody production, most likely due to less
      activation of T cells. In addition, no accumulation of inflammatory cells was
      observed in immunized mice, because endogenous Ang II would not activate T cells
      after immunization with Ang II-KLH. Taken together, these data indicate that
      vaccines targeting Ang II might be effective to decrease high BP and prevent
      cardiovascular complications without severe side effects.

PMID- 23544147
TI  - SipB-SipC complex is essential for translocon formation.
AB  - The delivery of effector proteins by Salmonella across the host cell membrane
      requires a subset of effectors secreted by the type III secretion system (TTSS)
      known as translocators. SipC and SipB are translocator proteins that are inserted
      into host membranes and presumably form a channel that translocates type III
      effectors into the host cell. The molecular events of how these translocators
      insert into the host cell membrane remain unknown. We have previously shown that
      the SipC C-terminal amino acid region (321-409) is required for the translocation
      of effectors into host cells. In this study, we demonstrate that the ability to
      form SipC-SipB complex is essential for their insertion into the host membrane.
      The SipB-interacting domain of SipC is near its C-terminal amino acid region (340
      409). In the absence of SipB, SipC was not detected in the membrane fraction.
      Furthermore, SipC mutants that no longer interact with SipB are defective in
      inserting into the host cell membrane. We propose a mechanism whereby SipC binds
      SipB through its C-terminal region to facilitate membrane-insertion and
      subsequent translocon formation in the host cell membrane.

PMID- 23544148
TI  - Transcriptional instability during evolving sepsis may limit biomarker based risk
      stratification.
AB  - BACKGROUND: Sepsis causes extensive morbidity and mortality in children
      worldwide. Prompt recognition and timely treatment of sepsis is critical in
      reducing morbidity and mortality. Genomic approaches are used to discover novel
      pathways, therapeutic targets and biomarkers. These may facilitate diagnosis and
      risk stratification to tailor treatment strategies. OBJECTIVE: To investigate the
      temporal gene expression during the evolution of sepsis induced multi-organ
      failure in response to a single organism, Neisseria meningitidis, in previously
      healthy children. METHOD: RNA was extracted from serial blood samples (6 time
      points over 48 hours from presentation) from five critically ill children with
      meningococcal sepsis. Extracted RNA was hybridized to Affymetrix arrays. The RNA
      underwent strict quality control and standardized quantitation. Gene expression
      results were analyzed using GeneSpring software and Ingenuity Pathway Analysis.
      RESULT: A marked variability in differential gene expression was observed between
      time points and between patients revealing dynamic expression changes during the
      evolution of sepsis. While there was evidence of time-dependent changes in
      expected gene networks including those involving immune responses and
      inflammatory pathways, temporal variation was also evident in specific
      "biomarkers" that have been proposed for diagnostic and risk stratification
      functions. The extent and nature of this variability was not readily explained by
      clinical phenotype. CONCLUSION: This is the first study of its kind detailing
      extensive expression changes in children during the evolution of sepsis. This
      highlights a limitation of static or single time point biomarker estimation.
      Serial estimations or more comprehensive network approaches may be required to
      optimize risk stratification in complex, time-critical conditions such as
      evolving sepsis.

PMID- 23544149
TI  - DNA methylation program in developing hippocampus and its alteration by alcohol.
AB  - During hippocampal development, the Cornus Ammonis (CA) and the dentate gyrus
      (DG) undergo waves of neurogenesis and neuronal migration and maturation
      independently. This stage is widely known to be vulnerable to environmental
      stresses, but its underlying mechanism is unclear. Alcohol exposure has been
      shown to alter the expression of genes that regulate the fate, survival,
      migration and differentiation of pyramidal and granule cells. Undermining this
      process might compromise hippocampal development underlying the learning and
      memory deficits known in Fetal Alcohol Spectrum Disorders (FASD). We have
      previously demonstrated that DNA methylation was programmed along with neural
      tube development. Here, we demonstrated that DNA methylation program (DMP)
      proceeded along with hippocampal neuronal differentiation and maturation, and how
      this DMP was affected by fetal alcohol exposure. C57BL/6 mice were treated with
      4% v/v ethanol through a liquid diet along with pair-fed and chow-fed controls
      from gestation day (E) 7 to E16. We found that a characteristic DMP, including 5
      methylcytidine (5mC), 5-hydroxylmethylcytidine (5hmC) and their binding proteins,
      led the hippocampal neuronal differentiation and maturation spatiotemporally as
      indicated by their phenotypic marks in the CA and DG pre- and post-natally.
      Alcohol hindered the acquisition and progression of methylation marks, and
      altered the chromatin translocation of these marks in the nucleus, which was
      correlated with developmental retardation.

PMID- 23544150
TI  - Evolution of Sindbis virus with a low-methionine-resistant phenotype is dependent
      both on a pre-existing mutation and on the methionine concentration in the
      medium.
AB  - SVlm21 is a mutant of Sindbis virus which was isolated by serial passage of virus
      in mosquito cells maintained in low-methionine medium; it therefore has a low
      methionine-resistant (LMR) phenotype. This phenotype requires mutations at nts
      319 and 321; these mutations result in Arg to Leu and Ser to Cys changes at
      positions 87 and 88 respectively in the viral methyl transferase, nsP1. To better
      understand the genesis of SVlm21, we carried out serial passages of viruses
      having only one of these amino acid changes, but in mosquito cells maintained in
      normal methionine-medium. Whether the passage was begun with SV319 or with SV321,
      the dominant virus population which emerged always acquired the second SVlm21
      amino acid change. However, when the passage was begun with virus having neither
      the nt 319 or the nt321 mutation, even after many passages neither of these
      mutations was seen in the passaged virus population. Virus with the LMR phenotype
      emerged earlier when the virus encoded a wild-type RDRP (passage 4) rather than
      the mutant RDRP encoded by SVpzf (passage 7). When the methionine concentration
      in the medium of mosquito cells was increased to 250 uM, more than 20 passages
      were required until the LMR phenotype predominated. Competition experiments were
      carried out to compare the relative fitness of SVlm21, SVwt, SV319 and SV321 to
      each other. Our results indicated that SVlm21 was dominant to SVwt, as well as to
      both SV319 and SV321. However, SV319 and SV321 were able to co-exist with SVwt
      implying that in these mixed infection the presence of SVwt inhibited the
      emergence of SVlm21. Finally, our experiments highlight how a virus population by
      mutation and selection can adapt to the intracellular concentration of a simple
      metabolite, S-adenosylmethionine.

PMID- 23544151
TI  - The force synergy of human digits in static and dynamic cylindrical grasps.
AB  - This study explores the force synergy of human digits in both static and dynamic
      cylindrical grasping conditions. The patterns of digit force distribution, error
      compensation, and the relationships among digit forces are examined to quantify
      the synergetic patterns and coordination of multi-finger movements. This study
      recruited 24 healthy participants to perform cylindrical grasps using a glass
      simulator under normal grasping and one-finger restricted conditions. Parameters
      such as the grasping force, patterns of digit force distribution, and the force
      coefficient of variation are determined. Correlation coefficients and principal
      component analysis (PCA) are used to estimate the synergy strength under the
      dynamic grasping condition. Specific distribution patterns of digit forces are
      identified for various conditions. The compensation of adjacent fingers for the
      force in the normal direction of an absent finger agrees with the principle of
      error compensation. For digit forces in anti-gravity directions, the distribution
      patterns vary significantly by participant. The forces exerted by the thumb are
      closely related to those exerted by other fingers under all conditions. The index
      middle and middle-ring finger pairs demonstrate a significant relationship. The
      PCA results show that the normal forces of digits are highly coordinated. This
      study reveals that normal force synergy exists under both static and dynamic
      cylindrical grasping conditions.

PMID- 23544152
TI  - Mild endoplasmic reticulum stress promotes retinal neovascularization via
      induction of BiP/GRP78.
AB  - Endoplasmic reticulum (ER) stress occurs as a result of accumulation of unfolded
      or misfolded proteins in the ER and is involved in the mechanisms of various
      diseases, such as cancer and neurodegeneration. The goal of the present study was
      to clarify the relationship between ER stress and pathological neovascularization
      in the retina. Proliferation and migration of human retinal microvascular
      endothelial cells (HRMEC) were assessed in the presence of ER stress inducers,
      such as tunicamycin and thapsigargin. The expression of ER chaperone
      immunoglobulin heavy-chain binding protein (BiP), known as Grp78, was evaluated
      by real time RT-PCR, immunostaining, and Western blotting. Tunicamycin or
      thapsigargin was injected into the intravitreal body of oxygen-induced
      retinopathy (OIR) model mice at postnatal day 14 (P14) and retinal
      neovascularization was quantified at P17. The expression and localization of BiP
      in the retina was also evaluated in the OIR model. Exposure to tunicamycin and
      thapsigargin increased the proliferation and migration of HRMEC. Tunicamycin
      enhanced the expression of BiP in HRMEC at both the mRNA level and at the protein
      level on the cell surface, and increased the formation of a BiP/T-cadherin
      immunocomplex. In OIR model mice, retinal neovascularization was accelerated by
      treatments with ER stress inducers. BiP was particularly observed in the
      pathological vasculature and retinal microvascular endothelial cells, and the
      increase of BiP expression was correlated with retinal neovascularization. In
      conclusion, ER stress may contribute to the formation of abnormal vasculature in
      the retina via BiP complexation with T-cadherin, which then promotes endothelial
      cell proliferation and migration.

PMID- 23544153
TI  - The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans
      during bacterial infection, by modulating the nematode's innate immune response.
AB  - The nematode Caenorhabditis elegans has in recent years been proven to be a
      powerful in vivo model for testing antimicrobial compounds. We report here that
      the alkaloid compound Harmane (2-methyl-beta-carboline) increases the lifespan of
      nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia
      coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown
      to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E.
      coli EDL933, we showed that Harmane does not lower the colonization burden in the
      nematodes. We also found that the expression of the putative immune effector gene
      F35E12.5 was up-regulated in response to Harmane treatment. This indicates that
      Harmane stimulates the innate immune response of the nematode; thereby increasing
      its lifespan during bacterial infection. Expression of F35E12.5 is predominantly
      regulated through the p38 MAPK pathway; however, intriguingly the lifespan
      extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This
      indicates that Harmane has a complex effect on the innate immune system of C.
      elegans. Harmane could therefore be a useful tool in the further research into C.
      elegans immunity. Since the innate immunity of C. elegans has a high degree of
      evolutionary conservation, drugs such as Harmane could also be possible
      alternatives to classic antibiotics. The C. elegans model could prove to be
      useful for selection and development of such drugs.

PMID- 23544154
TI  - Genomic analysis by deep sequencing of the probiotic Lactobacillus brevis KB290
      harboring nine plasmids reveals genomic stability.
AB  - We determined the complete genome sequence of Lactobacillus brevis KB290, a
      probiotic lactic acid bacterium isolated from a traditional Japanese fermented
      vegetable. The genome contained a 2,395,134-bp chromosome that housed 2,391
      protein-coding genes and nine plasmids that together accounted for 191 protein
      coding genes. KB290 contained no virulence factor genes, and several genes
      related to presumptive cell wall-associated polysaccharide biosynthesis and the
      stress response were present in L. brevis KB290 but not in the closely related L.
      brevis ATCC 367. Plasmid-curing experiments revealed that the presence of plasmid
      pKB290-1 was essential for the strain's gastrointestinal tract tolerance and
      tendency to aggregate. Using next-generation deep sequencing of current and 18
      year-old stock strains to detect low frequency variants, we evaluated genome
      stability. Deep sequencing of four periodic KB290 culture stocks with more than
      1,000-fold coverage revealed 3 mutation sites and 37 minority variation sites,
      indicating long-term stability and providing a useful method for assessing the
      stability of industrial bacteria at the nucleotide level.

PMID- 23544155
TI  - Attentional modulation of emotional conflict processing with flanker tasks.
AB  - Emotion processing has been shown to acquire priority by biasing allocation of
      attentional resources. Aversive images or fearful expressions are processed
      quickly and automatically. Many existing findings suggested that processing of
      emotional information was pre-attentive, largely immune from attentional control.
      Other studies argued that attention gated the processing of emotion. To tackle
      this controversy, the current study examined whether and to what degrees
      attention modulated processing of emotion using a stimulus-response-compatibility
      (SRC) paradigm. We conducted two flanker experiments using color scale faces in
      neutral expressions or gray scale faces in emotional expressions. We found SRC
      effects for all three dimensions (color, gender, and emotion) and SRC effects
      were larger when the conflicts were task relevant than when they were task
      irrelevant, suggesting that conflict processing of emotion was modulated by
      attention, similar to those of color and face identity (gender). However, task
      modulation on color SRC effect was significantly greater than that on gender or
      emotion SRC effect, indicating that processing of salient information was
      modulated by attention to a lesser degree than processing of non-emotional
      stimuli. We proposed that emotion processing can be influenced by attentional
      control, but at the same time salience of emotional information may bias toward
      bottom-up processing, rendering less top-down modulation than that on non
      emotional stimuli.

PMID- 23544156
TI  - The yield of essential oils in Melaleuca alternifolia (Myrtaceae) is regulated
      through transcript abundance of genes in the MEP pathway.
AB  - Medicinal tea tree (Melaleuca alternifolia) leaves contain large amounts of an
      essential oil, dominated by monoterpenes. Several enzymes of the chloroplastic
      methylerythritol phosphate (MEP) pathway are hypothesised to act as bottlenecks
      to the production of monoterpenes. We investigated, whether transcript abundance
      of genes encoding for enzymes of the MEP pathway were correlated with foliar
      terpenes in M. alternifolia using a population of 48 individuals that ranged in
      their oil concentration from 39 -122 mg x g DM(-1). Our study shows that most
      genes in the MEP pathway are co-regulated and that the expression of multiple
      genes within the MEP pathway is correlated with oil yield. Using multiple
      regression analysis, variation in expression of MEP pathway genes explained 87%
      of variation in foliar monoterpene concentrations. The data also suggest that
      sesquiterpenes in M. alternifolia are synthesised, at least in part, from
      isopentenyl pyrophosphate originating from the plastid via the MEP pathway.

PMID- 23544157
TI  - Dendritic cell podosome dynamics does not depend on the F-actin regulator SWAP
      70.
AB  - In addition to classical adhesion structures like filopodia or focal adhesions,
      dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F
      actin structures called podosomes. They are involved in cellular processes such
      as extracellular matrix degradation, bone resorption by osteoclasts, and trans
      cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes
      enable dendritic cells to degrade connective tissue by matrix metalloproteinases.
      SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of
      dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring
      formation and bone resorption. In the present study, we demonstrate that SWAP-70
      is not required for podosome formation and F-actin turnover in dendritic cells.
      Furthermore, we found that toll-like receptor 4 ligand induced podosome
      disassembly and podosome-mediated matrix degradation is not affected by SWAP-70
      in dendritic cells. Thus, podosome formation and function in dendritic cells is
      independent of SWAP-70.

PMID- 23544158
TI  - Efficient B cell depletion via diphtheria toxin in CD19-Cre/iDTR mice.
AB  - B cells were first discovered as antibody producing cells, as B-1 B cells and
      finally as effector cells. In recent years their capacity to serve as antigen
      presenting cells is increasingly appreciated, and better tools are needed to
      study their function. We have previously described a new mouse model, the iDTR
      mice, that allow for the Cre-mediated expression of the diphtheria toxin
      receptor, thus rendering cells that express the Cre-recombinase sensitivity to
      diphtheria toxin. Herein we describe a new mouse line, the B-DTR mice, where the
      CD19-Cre was crossed to the iDTR mice. B-DTR allows for the efficient and cost
      effective depletion of different B cell subpopulations, but only partially plasma
      cells. These mice can therefore be used to study the importance of B cells versus
      plasma cells in different immune responses and autoimmune diseases.

PMID- 23544159
TI  - Doxycycline-regulated 3T3-L1 preadipocyte cell line with inducible, stable
      expression of adenoviral E4orf1 gene: a cell model to study insulin-independent
      glucose disposal.
AB  - Impaired glycemic control and excessive adiposity are major risk factors for Type
      2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves
      glycemic control, independent of dietary fat intake or adiposity. It is
      impractical to use Ad36 for therapeutic action. Instead, we identified that
      E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of
      insulin signaling. To further evaluate the therapeutic potential of E4orf1 to
      improve glycemic control, we established a stable 3T3-L1 cell system in which
      E4orf1 expression can be regulated. The development and characterization of this
      cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by
      PCR was cloned into a tetracycline responsive element containing vector (pTRE
      Tight-E4orf1). Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified
      the one with the highest expression of E4orf1 in response to doxycycline
      treatment. Furthermore, using this inducible system we characterized the ability
      of E4orf1 to improve glucose disposal in a time dependent manner. This stable
      cell line offers a valuable resource to carefully study the novel signaling
      pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin.

PMID- 23544160
TI  - The efflux inhibitor phenylalanine-arginine beta-naphthylamide (PAbetaN)
      permeabilizes the outer membrane of gram-negative bacteria.
AB  - Active efflux of antimicrobial agents is a primary mechanism by which bacterial
      pathogens can become multidrug resistant. The combined use of efflux pump
      inhibitors (EPIs) with pump substrates is under exploration to overcome efflux
      mediated multidrug resistance. Phenylalanine-arginine beta-naphthylamide
      (PAbetaN) is a well-studied EPI that is routinely combined with fluoroquinolone
      antibiotics, but few studies have assessed its utility in combination with beta
      lactam antibiotics. The initial goal of this study was to assess the efficacy of
      beta-lactams in combination with PAbetaN against the opportunistic pathogen,
      Pseudomonas aeruginosa. PAbetaN reduced the minimal inhibitory concentrations
      (MICs) of several beta-lactam antibiotics against P. aeruginosa; however, the
      susceptibility changes were not due entirely to efflux inhibition. Upon PAbetaN
      treatment, intracellular levels of the chromosomally-encoded AmpC beta-lactamase
      that inactivates beta-lactam antibiotics were significantly reduced and AmpC
      levels in supernatants correspondingly increased, potentially due to
      permeabilization of the outer membrane. PAbetaN treatment caused a significant
      increase in uptake of 8-anilino-1-naphthylenesulfonic acid, a fluorescent
      hydrophobic probe, and sensitized P. aeruginosa to bulky antibiotics (e.g.
      vancomycin) that are normally incapable of crossing the outer membrane, as well
      as to detergent-like bile salts. Supplementation of growth media with magnesium
      to stabilize the outer membrane increased MICs in the presence of PAbetaN and
      restored resistance to vancomycin. Thus, PAbetaN permeabilizes bacterial
      membranes in a concentration-dependent manner at levels below those typically
      used in combination studies, and this additional mode of action should be
      considered when using PAbetaN as a control for efflux studies.

PMID- 23544161
TI  - Electrophysiological study of supraspinal input and spinal output of cat's
      subnucleus reticularis dorsalis (SRD) neurons.
AB  - This work addressed the study of subnucleus reticularis dorsalis (SRD) neurons in
      relation to their supraspinal input and the spinal terminating sites of their
      descending axons. SRD extracellular unitary recordings from anesthetized cats
      aimed to specifically test, 1) the rostrocaudal segmental level reached by axons
      of spinally projecting (SPr) neurons collateralizing or not to or through the
      ipsilateral nucleus reticularis gigantocellularis (NRGc), 2) whether SPr fibers
      bifurcate to the thalamus, and 3) the effects exerted on SRD cells by
      electrically stimulating the locus coeruleus, the periaqueductal grey, the
      nucleus raphe magnus, and the mesencephalic locomotor region. From a total of 191
      SPr fibers tested to cervical 2 (Ce2), thoracic 5 (Th5) and lumbar5 (Lu5)
      stimulation, 81 ended between Ce2 and Th5 with 39 of them branching to or through
      the NRGc; 21/49 terminating between Th5 and Lu5 collateralized to or through the
      same nucleus, as did 34/61 reaching Lu5. The mean antidromic conduction velocity
      of SPr fibers slowed in the more proximal segments and increased with terminating
      distance along the cord. None of the 110 axons tested sent collaterals to the
      thalamus; instead thalamic stimulation induced long-latency polysynaptic
      responses in most cells but also short-latency, presumed monosynaptic, in 7.9% of
      the tested neurons (18/227). Antidromic and orthodromic spikes were elicited from
      the locus coeruleus and nucleus raphe magnus, but exclusively orthodromic
      responses were observed following stimulation of the periaqueductal gray or
      mesencephalic locomotor region. The results suggest that information from pain
      and-motor-related supraspinal structures converge on SRD cells that through SPr
      axons having conduction velocities tuned to their length may affect rostral and
      caudal spinal cord neurons at fixed delays, both directly and in parallel through
      different descending systems. The SRD will thus play a dual functional role by
      simultaneously regulating dorsal horn ascending noxious information and pain
      related motor responses.

PMID- 23544162
TI  - 2-hydroxyglutarate as a magnetic resonance biomarker for glioma subtyping.
AB  - Mutations in the isocitrate dehydrogenase (IDH) genes are frequently found in
      gliomas and in a fraction of acute myeloid leukemia patients. This results in the
      production of an oncometabolite, 2-hydroxyglutarate (2-HG). Glioma patients
      harboring IDH mutations have a longer survival than their wild-type counterparts.
      2-HG has been detected noninvasively in gliomas with IDH mutations using magnetic
      resonance spectroscopy (MRS), suggesting its potential clinical relevance for
      identifying glioma subtypes with better prognosis. In this paper, the recent
      developments in the MRS detection of the 2-HG in gliomas are reviewed, including
      the therapeutic potentials and translational values.

PMID- 23544163
TI  - LCN2 and TIMP1 as Potential Serum Markers for the Early Detection of Familial
      Pancreatic Cancer.
AB  - High-risk individuals of familial pancreatic cancer (FPC) families are considered
      to be good candidates for screening programs to detect early PC or its high-grade
      precursor lesions, especially pancreatic intraepithelial neoplasia (PanIN) 2/3
      lesions. There is a definite need for diagnostic markers as neither reliable
      imaging methods nor biomarkers are available to detect these lesions. On the
      basis of a literature search, the potential serum markers neutrophil gelatinase
      associated lipocalin (LCN2), metallopeptidase inhibitor 1 (TIMP1), chemokine (C-X
      C motif) ligand 16 (CXCL16), IGFBP4, and iC3a, which were first tested in
      transgenic KrasLSL.(G12D/+);p53(R172H/+);Pdx1-Cre mice, were identified. ELISA
      analyses of LCN2, TIMP1, and CXCL16 revealed significantly higher levels in mice
      with PanIN2/3 lesions or PC compared to mice with normal pancreata or PanIN1
      lesions. Analysis of preoperative human serum samples from patients with sporadic
      PC (n = 61), hereditary PC (n = 24), chronic pancreatitis (n = 28), pancreatic
      neuroendocrine tumors (n = 11), and FPC patients with histologically proven
      multifocal PanIN2/3 lesions (n = 3), as well as healthy control subjects (n =
      20), confirmed significantly higher serum levels of LCN2 and TIMP1 in patients
      with PC and multifocal PanIN2/3 lesions. The combination of LCN2 and TIMP1 as a
      diagnostic test for the detection of PC had a sensitivity, specificity, and
      positive predictive value of 100% each. Although this preliminary finding needs
      to be validated in a large series of individuals at high risk for FPC, serum
      measurement of LCN2 and TIMP1 might be a promising screening tool.

PMID- 23544164
TI  - Fusicoccin a, a phytotoxic carbotricyclic diterpene glucoside of fungal origin,
      reduces proliferation and invasion of glioblastoma cells by targeting multiple
      tyrosine kinases.
AB  - Glioblastoma multiforme (GBM) is a deadly cancer that possesses an intrinsic
      resistance to pro-apoptotic insults, such as conventional chemotherapy and
      radiotherapy, and diffusely invades the brain parenchyma, which renders it
      elusive to total surgical resection. We found that fusicoccin A, a fungal
      metabolite from Fusicoccum amygdali, decreased the proliferation and migration of
      human GBM cell lines in vitro, including several cell lines that exhibit varying
      degrees of resistance to pro-apoptotic stimuli. The data demonstrate that
      fusicoccin A inhibits GBM cell proliferation by decreasing growth rates and
      increasing the duration of cell division and also decreases two-dimensional
      (measured by quantitative video microscopy) and three-dimensional (measured by
      Boyden chamber assays) migration. These effects of fusicoccin A treatment
      translated into structural changes in actin cytoskeletal organization and a loss
      of GBM cell adhesion. Therefore, fusicoccin A exerts cytostatic effects but low
      cytotoxic effects (as demonstrated by flow cytometry). These cytostatic effects
      can partly be explained by the fact that fusicoccin inhibits the activities of a
      dozen kinases, including focal adhesion kinase (FAK), that have been implicated
      in cell proliferation and migration. Overexpression of FAK, a nonreceptor protein
      tyrosine kinase, directly correlates with the invasive phenotype of aggressive
      human gliomas because FAK promotes cell proliferation and migration. Fusicoccin A
      led to the down-regulation of FAK tyrosine phosphorylation, which occurred in
      both normoxic and hypoxic GBM cell culture conditions. In conclusion, the current
      study identifies a novel compound that could be used as a chemical template for
      generating cytostatic compounds designed to combat GBM.

PMID- 23544165
TI  - CXCR4 Expression and Treatment with SDF-1alpha or Plerixafor Modulate
      Proliferation and Chemosensitivity of Colon Cancer Cells.
AB  - BACKGROUND: Signaling through stromal cell-derived factor-1alpha (SDF-1alpha),
      strongly secreted by bone marrow stromal cells and the CXC chemokine receptor 4
      (CXCR4) exposed on tumor cells has pivotal roles in proliferation, metastasis,
      and tumor cell "dormancy." Dormancy is associated with cytostatic drug resistance
      and is probably a property of tumor stem cells and minimal residual disease.
      Thus, hampering the SDF-1alpha/CXCR4 cross talk by a CXCR4 antagonist like
      Plerixafor (AMD3100) should overcome tumor cell dormancy bymobilization of tumor
      cells from "sanctuary" niches. Our aim was to elucidate the direct effects
      exerted by SDF-1alpha and Plerixafor on proliferation, chemosensitivity, and
      apoptosis of CXCR4-expressing tumor cells. METHODS: The ability of SDF-1alpha and
      Plerixafor to regulate intracellular signaling, proliferation, and invasion was
      investigated using two colon cancer cell lines (HT-29 and SW480) with either high
      endogenous or lentiviral expression of CXCR4 compared to their respective low
      CXCR4-expressing counterparts as a model system. Efficacy of Plerixafor on
      sensitivity of these cell lines against 5-fluorouracil, irinotecan, or
      oxaliplatin was determined in a cell viability assay as well as stroma-dependent
      cytotoxicity and apoptosis assays. RESULTS: SDF-1alpha increased proliferation,
      invasion, and ERK signaling of endogenously and lentivirally CXCR4-expressing
      cells. Exposure to Plerixafor reduced proliferation, invasion, and extracellular
      signal-regulated kinase 1/2 (ERK1/2) signaling. Combination of chemotherapy with
      Plerixafor showed an additive effect on chemosensitivity and apoptosis in CXCR4
      overexpressing cells. An SDF-1-secreting feeder layer provideda"protective niche"
      for CXCR4-overexpressing cells resulting in decreased chemosensitivity.
      CONCLUSION: CXCR4-antagonistic therapy mobilizes and additionally sensitizes
      tumor cells toward cytoreductive chemotherapy.

PMID- 23544166
TI  - DW-MRI as a Predictive Biomarker of Radiosensitization of GBM through Targeted
      Inhibition of Checkpoint Kinases.
AB  - PURPOSE: The inherent treatment resistance of glioblastoma (GBM) can involve
      multiple mechanisms including checkpoint kinase (Chk1/2)-mediated increased DNA
      repair capability, which can attenuate the effects of genotoxic chemotherapies
      and radiation. The goal of this study was to evaluate diffusion-weighted magnetic
      resonance imaging (DW-MRI) as a biomarker for Chk1/2 inhibitors in combination
      with radiation for enhancement of treatment efficacy in GBM. EXPERIMENTAL DESIGN:
      We evaluated a specific small molecule inhibitor of Chk1/2, AZD7762, in
      combination with radiation using in vitro human cell lines and in vivo using a
      genetically engineered GBM mouse model. DW-MRI and T1-contrast MRI were used to
      follow treatment effects on intracranial tumor cellularity and growth rates,
      respectively. RESULTS: AZD7762 inhibited clonal proliferation in a panel of GBM
      cell lines and increased radiosensitivity in p53-mutated GBM cell lines to a
      greater extent compared to p53 wild-type cells. In vivo efficacy of AZD7762
      demonstrated a dose-dependent inhibitory effect on GBM tumor growth rate and a
      reduction in tumor cellularity based on DW-MRI scans along with enhancement of
      radiation efficacy. CONCLUSION: DW-MRI was found to be a useful imaging biomarker
      for the detection of radiosensitization through inhibition of checkpoint kinases.
      Chk1/2 inhibition resulted in antiproliferative activity, prevention of DNA
      damage-induced repair, and radiosensitization in preclinical GBM tumor models,
      both in vitro and in vivo. The effects were found to be maximal in p53-mutated
      GBM cells. These results provide the rationale for integration of DW-MRI in
      clinical translation of Chk1/2 inhibition with radiation for the treatment of
      GBM.

PMID- 23544167
TI  - Endoplasmic reticulum stress plays a pivotal role in cell death mediated by the
      pan-deacetylase inhibitor panobinostat in human hepatocellular cancer cells.
AB  - Panobinostat, a pan-deacetylase inhibitor, represents a novel therapeutic option
      for cancer diseases. Besides its ability to block histone deacetylases (HDACs) by
      promoting histone hyperacetylation, panobinostat interferes with several cell
      death pathways providing a potential efficacy against tumors. We have previously
      demonstrated that panobinostat has a potent apoptotic activity in vitro and
      causes a significant growth delay of hepatocellular carcinoma (HCC) tumor
      xenografts in nude mice models. Here, we show that treatment with panobinostat is
      able to induce noncanonical apoptotic cell death in HepG2 and in Hep3B cells,
      involving the endoplasmic reticulum (ER) stress by up-regulation of the molecular
      chaperone binding immunoglobulin protein/glucose-regulated protein 78, activation
      of eukaryotic initiation factor 2alpha-activating transcription factor 4 (tax
      responsive enhancer element B67) and inositol requiring 1alpha-X-box binding
      protein 1 factors, strong increase and nuclear translocation of the transcription
      factor C/EBP homologous protein/growth arrest and DNA damage-inducible gene 153,
      and involvement of c-Jun N-terminal kinase. These signaling cascades culminate
      into the activation of the ER-located caspase-4/12 and of executioner caspases,
      which finally lead to cell demise. Our results clearly show that panobinostat
      induces an alternative ER stress-mediated cell death pathway in HCC cells,
      independent of the p53 status.

PMID- 23544168
TI  - Imatinib and Dasatinib Inhibit Hemangiosarcoma and Implicate PDGFR-beta and Src
      in Tumor Growth.
AB  - Hemangiosarcoma, a natural model of human angiosarcoma, is an aggressive vascular
      tumor diagnosed commonly in dogs. The documented expression of several receptor
      tyrosine kinases (RTKs) by these tumors makes them attractive targets for
      therapeutic intervention using tyrosine kinase inhibitors (TKIs). However, we
      possess limited knowledge of the effects of TKIs on hemangiosarcoma as well as
      other soft tissue sarcomas. We report here on the use of the TKIs imatinib and
      dasatinib in canine hemangiosarcoma and their effects on platelet-derived growth
      factor receptor beta (PDGFR-beta) and Src inhibition. Both TKIs reduced cell
      viability, but dasatinib was markedly more potent in this regard, mediating
      cytotoxic effects orders of magnitude greater than imatinib. Dasatinib also
      inhibited the phosphorylation of the shared PDGFR-beta target at a concentration
      approximately 1000 times less than that needed by imatinib and effectively
      blocked Src phosphorylation. Both inhibitors augmented the response to
      doxorubicin, suggesting that clinical responses likely will be improved using
      both drugs in combination; however, dasatinib was significantly (P < .05) more
      effective in this context. Despite the higher concentrations needed in cell-based
      assays, imatinib significantly inhibited tumor growth (P < .05) in a tumor
      xenograft model, highlighting that disruption of PDGFR-beta/PDGF signaling may be
      important in targeting the angiogenic nature of these tumors. Treatment of a dog
      with spontaneously occurring hemangiosarcoma established that clinically
      achievable doses of dasatinib may be realized in dogs and provides a means to
      investigate the effect of TKIs on soft tissue sarcomas in a large animal model.

PMID- 23544169
TI  - Radiosensitization of Glioblastoma Cell Lines by the Dual PI3K and mTOR Inhibitor
      NVP-BEZ235 Depends on Drug-Irradiation Schedule.
AB  - Previous studies have shown that the dual phosphatidylinositide 3
      kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor NVP-BEZ235
      radiosensitizes tumor cells if added shortly before ionizing radiation (IR) and
      kept in culture medium thereafter. The present study explores the impact of
      inhibitor and IR schedule on the radiosensitizing ability of NVP-BEZ235 in four
      human glioblastoma cell lines. Two different drug-IR treatment schedules were
      compared. In schedule I, cells were treated with NVP-BEZ235 for 24 hours before
      IR and the drug was removed before IR. In schedule II, the cells were exposed to
      NVP-BEZ235 1 hour before, during, and up to 48 hours after IR. The cellular
      response was analyzed by colony counts, expression of marker proteins of the
      PI3K/AKT/mTOR pathway, cell cycle, and DNA damage. We found that under schedule
      I, NVP-BEZ235 did not radiosensitize cells, which were mostly arrested in G1
      phase during IR exposure. In addition, the drug-pretreated and irradiated cells
      exhibited less DNA damage but increased expressions of phospho-AKT and phospho
      mTOR, compared to controls. In contrast, NVP-BEZ235 strongly enhanced the
      radiosensitivity of cells treated according to schedule II. Possible reasons of
      radiosensitization by NVP-BEZ235 under schedule II might be the protracted DNA
      repair, prolonged G2/M arrest, and, to some extent, apoptosis. In addition, the
      PI3K pathway was downregulated by the NVP-BEZ235 at the time of irradiation under
      schedule II, as contrasted with its activation in schedule I. We found that,
      depending on the drug-IR schedule, the NVP-BEZ235 can act either as a strong
      radiosensitizer or as a cytostatic agent in glioblastoma cells.

PMID- 23544170
TI  - Down-regulation of miR-21 Induces Differentiation of Chemoresistant Colon Cancer
      Cells and Enhances Susceptibility to Therapeutic Regimens.
AB  - MicroRNAs are endogenous posttranscriptional modulators that negatively control
      the expression of their target genes and play an important role in the
      development and progression of many malignancies, including colorectal carcinoma.
      In particular, expression of microRNA-21 (miR-21) is greatly increased in
      chemotherapy-resistant (CR) colon cancer cells that are enriched in
      undifferentiated cancer stem/stem-like cells (CSCs/CSLCs). We hypothesize that
      miR-21 plays a critical role in regulating differentiation of CR colon cancer
      cells. Indeed, we observed that downregulation of miR-21 in CR colon cancer cells
      (HCT-116 or HT-29) by antisense miR-21 induced differentiation, as evidenced by
      marked increases in cytokeratin-20 (CK-20) expression and alkaline phosphatase
      activity. These changes were accompanied by a significant reduction in the
      expression of colon CSC/CSLC marker CD44, colonosphere formation, and T-cell
      factor/lymphoid enhancer factor (TCF/LEF) activity but increased the expression
      of proapoptotic programmed cell death 4 gene. Induction of differentiation
      greatly increased sensitivity of CR colon cancer cells to the growth inhibitory
      properties of all three regimens tested: 5-fluorouracil + oxaliplatin (FUOX),
      difluorinated curcumin (CDF), and the combination of CDF and FUOX. However, the
      magnitude of inhibition of growth by either CDF (75%) alone or CDF + FUOX (80%)
      was much higher than that observed with only FUOX (40%). Growth inhibition by CDF
      and CDF + FUOX in differentiating CR colon cancer cells was associated with a 98%
      to 99% reduction in the expression of CD44 and epidermal growth factor receptor
      (EGFR). However, down-regulation of CK-20 in CR colon cancer cells produced no
      significant change in cellular growth in the absence or presence of FUOX, when
      compared with the corresponding controls. The current observation suggests that
      CDF and CDF + FUOX are highly effective in inhibiting growth and reducing colon
      CSCs/CSLCs in anti-miR-21-induced differentiating CR colon cancer cells and
      supports our contention that differentiation enhances susceptibility of CR cancer
      cells to conventional and nonconventional therapeutic regimen.

PMID- 23544171
TI  - In Vitro and In Vivo Analysis of RTK Inhibitor Efficacy and Identification of Its
      Novel Targets in Glioblastomas.
AB  - Treatment for glioblastoma consists of radiotherapy and temozolomide-based
      chemotherapy. However, virtually all patients recur, leading to a fatal outcome.
      Receptor tyrosine kinase (RTK)-targeted therapy has been the focus of attention
      in novel treatment options for these patients. Here, we compared the efficacy of
      imatinib, sunitinib, and cediranib in glioblastoma models. In the present work,
      the biologic effect of the drugs was screened by viability, cell cycle,
      apoptosis, migration, and invasion in vitro assays or in vivo by chick
      chorioallantoic membrane assay. Intracellular signaling was assessed by Western
      blot and the RTK targets were identified using phospho-RTK arrays. The amplified
      status of KIT, PDGFRA, and VEGFR2 genes was assessed by quantitative polymerase
      chain reaction. In a panel of 10 glioblastoma cell lines, we showed that
      cediranib was the most potent. In addition, cediranib and sunitinib
      synergistically sensitize the cells to temozolomide. Cediranib efficacy was shown
      to associate with higher cytostatic and unique cytotoxic effects in vitro and
      both antitumoral and antiangiogenic activity in vivo, which could associate with
      its great capacity to inhibit mitogen-activated protein kinase (MAPK) and AKT
      pathways. The molecular status of KIT, PDGFRA, and VEGFR2 did not predict
      glioblastoma cell responsiveness to any of the RTK inhibitors. Importantly,
      phospho-RTK arrays revealed novel targets for cediranib and sunitinib therapy. In
      conclusion, the novel targets found may be of value as future biomarkers for
      therapy response in glioblastoma and lead to the rational selection of patients
      for effective molecular targeted treatment.

PMID- 23544172
TI  - Notch pathway is activated by MAPK signaling and influences papillary thyroid
      cancer proliferation.
AB  - Mutually exclusive genetic alterations in the RET, RAS, or BRAF genes, which
      result in constitutively active mitogen-activated protein kinase (MAPK)
      signaling, are present in about 70% of papillary thyroid carcinomas (PTCs).
      However, the effect of MAPK activation on other signaling pathways involved in
      oncogenic transformation, such as Notch, remains unclear. In this study, we
      tested the hypothesis that the MAPK pathway regulates Notch signaling and that
      Notch signaling plays a role in PTC cell proliferation. Conditional induction of
      MAPK signaling oncogenes RET/PTC3 or BRAF(T1799A) in normal rat thyroid cell line
      mediated activation of Notch signaling, upregulating Notch1 receptor and Hes1,
      the downstream effector of Notch pathway. Conversely, pharmacological inhibition
      of MAPK reduced Notch signaling in PTC cell. Thyroid tumor samples from
      transgenic mice expressing BRAF(T1799A) and primary human PTC samples showed high
      levels of Notch1 expression. Down-regulation of Notch signaling by gamma
      secretase inhibitor (GSI) or NOTCH1 RNA interference reduces PTC cell
      proliferation. Moreover, the combination of GSI with a MAPK inhibitor enhanced
      the growth suppression in PTC cells. This study revealed that RET/PTC and
      BRAF(T1799A) activate Notch signaling and promote tumor growth in thyroid
      follicular cell. Taken together, these data suggest that Notch signaling may be
      explored as an adjuvant therapy for thyroid papillary cancer.

PMID- 23544173
TI  - FAK Inhibition Decreases Hepatoblastoma Survival Both In Vitro and In Vivo.
AB  - Hepatoblastoma is the most frequently diagnosed liver tumor of childhood, and
      children with advanced, metastatic or relapsed disease have a disease-free
      survival rate under 50%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine
      kinase that is important in many facets of tumor development and progression. FAK
      has been found in other pediatric solid tumors and in adult hepatocellular
      carcinoma, leading us to hypothesize that FAK would be present in hepatoblastoma
      and would impact its cellular survival. In the current study, we showed that FAK
      was present and phosphorylated in human hepatoblastoma tumor specimens. We also
      examined the effects of FAK inhibition upon hepatoblastoma cells using a number
      of parallel approaches to block FAK including RNAi and small molecule FAK
      inhibitors. FAK inhibition resulted in decreased cellular survival, invasion, and
      migration and increased apoptosis. Further, small molecule inhibition of FAK led
      to decreased tumor growth in a nude mouse xenograft model of hepatoblastoma. The
      findings from this study will help to further our understanding of the regulation
      of hepatoblastoma tumorigenesis and may provide desperately needed novel
      therapeutic strategies and targets for aggressive, recurrent, or metastatic
      hepatoblastomas.

PMID- 23544174
TI  - CXCR2 macromolecular complex in pancreatic cancer: a potential therapeutic target
      in tumor growth.
AB  - The signaling mediated by the chemokine receptor CXC chemokine receptor 2 (CXCR2)
      plays an important role in promoting the progression of many cancers, including
      pancreatic cancer, one of the most lethal human malignancies. CXCR2 possesses a
      consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl termini, which might
      interact with potential PDZ scaffold/adaptor proteins. We have previously
      reported that CXCR2 PDZ motif-mediated protein interaction is an important
      regulator for neutrophil functions. Here, using a series of biochemical assays,
      we demonstrate that CXCR2 is physically coupled to its downstream effector
      phospholipase C-beta3 (PLC-beta3) that is mediated by PDZ scaffold protein
      Na(+)/H(+) exchange regulatory factor 1 (NHERF1) into a macromolecular signaling
      complex both in vitro and in pancreatic cancer cells. We also observe that
      disrupting the CXCR2 complex, by gene delivery or peptide delivery of exogenous
      CXCR2 C-tail, significantly inhibits the biologic functions of pancreatic cancer
      cells (i.e., proliferation and invasion) in a PDZ motif-dependent manner. In
      addition, using a human pancreatic tumor xenograft model, we show that gene
      delivery of CXCR2 C-tail sequence (containing the PDZ motif) by adeno-associated
      virus type 2 viral vector potently suppresses human pancreatic tumor growth in
      immunodeficient mice. In summary, our results suggest the existence of a physical
      and functional coupling of CXCR2 and PLC-beta3 mediated through NHERF1, forming a
      macromolecular complex that is critical for efficient and specific CXCR2
      signaling in pancreatic cancer progression. Disrupting this CXCR2 complex could
      represent a novel and effective treatment strategy against pancreatic cancer.

PMID- 23544175
TI  - Impossible or merely difficult? Two grand challenges from a biologist's
      perspective.
AB  - Here I propose two grand challenges for medicinal chemists: the deorphanization
      of orphan GPCRs via in silico methods and the design of multi-target drugs with
      enhanced safety and efficacy over current medications.

PMID- 23544176
TI  - Isn't it the Time for Working on Public Health Guidance in Health System of Iran?

PMID- 23544177
TI  - Blister beetle dermatitis: few observations helping in diagnosis.

PMID- 23544178
TI  - Utility of two novel multiplexing assays for the detection of gastrointestinal
      pathogens - a first experience.
AB  - BACKGROUND: Cause for gastroenteritis range from viral, bacterial to parasitic
      pathogens. Rapid Multiplexing techniques like ProGastro_SSCS and xTAG_GPP can
      detect broad panels of pathogens simultaneously. We performed a field test with a
      total number of 347 stool samples from adult hospitalized patients that were
      tested with the Luminex xTAG GPP assay; of the 157 samples positively tested for
      at least one pathogen by xTAG GPP a total number of 30 samples was retested with
      the ProGastro SSCS assay. Assays were compared to standard routine diagnostics.
      FINDINGS: Multiplexing significantly reduced the time to the initial
      identification of a pathogen. Moreover, multiplexing detected pathogens for which
      a diagnostic assays was not requested by the physician and thus may be an
      important tool for avoiding nosocomial outbreaks. CONCLUSION: This first
      frontline approach with these assays approves their utility compared to
      conventional microbiological methods.

PMID- 23544179
TI  - Diabetes and Cardiovascular Disease: Original Insights from the Framingham Heart
      Study.
AB  - The role of diabetes in the pathogenesis of cardiovascular disease (CVD) was
      unclear until 1979 when Kannel et al used data from the Framingham Heart Study
      (FHS) to identify diabetes as a major cardiovascular risk factor. It was also one
      of the first studies to demonstrate the higher risk of CVD in women with diabetes
      compared to men with diabetes. Since then, multiple studies have been done to
      recognize and curtail cardiovascular risk factors such as smoking, obesity,
      hypertension, hyperlipidemia, and insulin resistance. This review will examine
      the contribution of the Kannel article and subsequent studies in defining the
      contribution of several risk factors on cardiovascular disease.

PMID- 23544180
TI  - Nosocomial Candida infection in a rural tertiary care hospital.

PMID- 23544181
TI  - Hyponatraemia in head injuries caused by road traffic accidents.

PMID- 23544182
TI  - The Peak Expiratory Flow Rate (PEFR): the Effect of Stress in a Geriatric
      Population of Chennai- A Pilot Study.

PMID- 23544183
TI  - The respiratory health of rural Indian women: does the domestic cooking fuel
      really matter?

PMID- 23544185
TI  - ED-based protocols speed care to sickle cell patients, reduce repeat ED visits,
      and discharge admitted patients earlier.
AB  - Patients with sickle cell disease commonly experience episodes of extreme pain
      that prompt them to seek care in the ED. However, emergency providers sometimes
      mistake these patients as drug-seekers, delaying effective pain relief and often
      resulting in under-treatment that can prolong suffering and result in repeat
      visits. Experts recommend development of specialized sickle cell protocols that
      fast-track patients toward the care they need, and give patients some control
      over how much pain medication they need. Experts say ED-based sickle cell
      protocols can improve patient and provider satisfaction while also reducing
      repeat ED visits as well as length-of-stay when patients need to be admitted. New
      research suggests that ED use spikes as sickle patients reach adulthood. Experts
      say ED providers can play a role in helping these patients transition into
      effective primary care settings.

PMID- 23544184
TI  - 18F-FDG PET/CT for the assessment of myocardial sarcoidosis.
AB  - Cardiac involvement portends a poor prognosis inpatients with sarcoidosis.
      However, due to the non specific clinical manifestations of the disease, patchy
      myocardial involvement, and the limited diagnostic yield of diagnostic tests,
      early diagnosis of cardiac sarcoidosis has been exceedingly difficult. As a
      result, there is no standardized approach for the early diagnosis of cardiac
      sarcoidosis. Imaging modalities that can both identify disease and predict
      response to therapy are paramount to improve management of cardiac sarcoidosis.
      18F-FDG PET has many practical advantages in assessing disease activity and
      monitoring treatment response in patients with cardiac sarcoidosis. Accumulating
      data support the growing role of 18F-fluorodeoxyglucose (18F-FDG)PET in the
      diagnosis and risk stratification of patients with cardiac sarcoidosis.

PMID- 23544186
TI  - Study: emergency providers can play a role in helping sickle cell patients
      transition into effective primary care as they reach adulthood.

PMID- 23544187
TI  - Collaborative effort in Washington state slashes non-essential use of the ED by
      Medicaid patients, delivering millions in projected savings.
AB  - Early data suggest a coordinated, state-wide effort has reduced non-essential use
      of the ED by 10% among Medicaid recipients in Washington state, and is projected
      to save the state an estimated $31 million in the first year of the approach. The
      effort includes the adoption of seven best practices by hospitals across the
      state.These include the creation of an Emergency Department Information Exchange,
      so that EDs can immediately access a patient's utilization history, strict
      narcotic prescribing guidelines, and regular feedback reports to hospitals
      regarding ED utilization patterns. The effort was prompted by threats by the
      state legislature to limit Medicaid payments for ED visits deemed not medically
      necessary in the emergency setting. The legislature backed down when emergency
      physicians in the state countered with their own proposal to reduce nonessential
      use of the ED. They worked with other health care groups in the state to develop
      the plan. Data on the first six months of the effort are included in a report to
      the state legislature by the Washington State Health Care Authority. Among the
      findings are a 23% reduction in ED visits among Medicaid recipients with five or
      more visits, a 250% increase in providers who have registered with the state's
      Prescription Monitoring Program, aimed at identifying patients with narcotic
      seeking behavior, and a doubling in the number of shared care plans, intended to
      improve care coordination. Emergency providers say big challenges remain,
      including a need for more resources for patients with mental health and dental
      care needs.

PMID- 23544188
TI  - Experts: despite time constraints, motivational interviewing techniques can have
      lasting impact on drinkers, drug abusers.
AB  - Researchers have found that the Brief Negotiation Interview (BNI), a tool
      developed at Yale School of Medicine in New Haven, CT, can curb harmful drinking
      in patients when the tool is used with these patients in the emergency setting.
      Further, by using the same motivational interviewing techniques employed in the
      tool, experts say providers can help patients curb other harmful behaviors as
      well. The BNI consists of a series of questions that take about seven minutes to
      discuss with patients. The tool prompts patients to come up with their own
      reasons for changing harmful behaviors. To implement the BNI, emergency providers
      need training and constant reinforcement. Ideally, experts say the motivational
      interviewing techniques employed in the BNI need to become routine to have a
      lasting impact on patient care.

PMID- 23544189
TI  - Elements for successful functional result after surgical treatment of intra
      articular distal humeral fractures.
AB  - Intra-articular distal humeral fractures (DHF) present great challenge to an
      orthopedic-trauma surgeon. We analyzed the relationship between functional
      results of DHF surgical treatment and elements that can affect patient recovery.
      During the 5-year follow-up study, 32 patients were treated for DHF at our Trauma
      Department, 30 of them by surgical procedure. Functional results of surgical
      treatment were scored according to the Jupiter criteria. According to the A-O
      classification of DHF, there were 11 type A fractures, 5 type B fractures and 14
      type C fractures. Postoperative complications were infections, neural lesions,
      inadequate healing, and instability of osteosynthesis. Analysis of functional
      results in patients with operated C type fractures according to different
      elements influencing postoperative result revealed correct healing in 74% of
      patients, which was statistically significantly higher than the percentage of
      unsatisfactory results (p < 0.05). Study results provided evidence for patient
      age, sex, infection, neural function preservation, successful and rigid fixation,
      anatomical reconstruction of articular surface, and early rehabilitation to be
      significant elements for successful functional recovery.

PMID- 23544190
TI  - Response to Dr. Ambrosetto.

PMID- 23544191
TI  - Optimizing outcomes for octogenarians with invasive bladder cancer: One size does
      not fit all.

PMID- 23544192
TI  - No ischemia robotic partial nephrectomy: why and why not?

PMID- 23544193
TI  - Publishing: Open to possibilities.

PMID- 23544194
TI  - Author response.

PMID- 23544195
TI  - Author response.

PMID- 23544196
TI  - Under the gun.

PMID- 23544197
TI  - Disciplinary action.

PMID- 23544198
TI  - Push the boat out.

PMID- 23544199
TI  - Response to comment on "The role of naive T cell precursor frequency and
      recruitment in dictating immune response magnitude".

PMID- 23544201
TI  - Reply to T.G. Karrison.

PMID- 23544200
TI  - Ranibizumab for edema of the macula in diabetes study: 3-year outcomes and the
      need for prolonged frequent treatment.
AB  - OBJECTIVE: To assess the benefit of increased follow-up and treatment with
      ranibizumab between months 24 and 36 in the Ranibizumab for Edema of the Macula
      in Diabetes (READ-2) Study. DESIGN: Prospective, interventional, multicenter
      follow-up of a randomized clinical trial. METHODS: Patients who agreed to
      participate between months 24 and 36 (ranibizumab, 28 patients; laser, 22; and
      ranibizumab + laser, 24) returned monthly and received ranibizumab, 0.5 mg, if
      foveal thickness (FTH, center subfield thickness) was 250 MUm or greater. Main
      outcome measures were improvement in best-corrected visual acuity (BCVA) and
      reduction in FTH between months 24 and 36. RESULTS: Mean improvement from the
      baseline BCVA in the ranibizumab group was 10.3 letters at month 36 vs 7.2
      letters at month 24 (DeltaBCVA letters = 3.1, P = .009), and FTH at month 36 was
      282 MUm vs 352 MUm at month 24 (DeltaFTH = 70 MUm, P = .006). Changes in BCVA and
      FTH in the laser group (-1.6 letters and -36 MUm, respectively) and the
      ranibizumab + laser group (+2.0 letters and -24 MUm) were not statistically
      significant. The mean number of ranibizumab injections was significantly greater
      in the ranibizumab group compared with the laser group (5.4 vs 2.3 injections, P
      = .008) but not compared with the ranibizumab + laser group (3.3, P = .11).
      CONCLUSIONS: More aggressive treatment with ranibizumab during year 3 resulted in
      a reduction in mean FTH and improvement in BCVA in the ranibizumab group. More
      extensive focal/grid laser therapy in the other 2 groups may have reduced the
      need for more frequent ranibizumab injections to control edema. APPLICATION TO
      CLINICAL PRACTICE: Long-term visual outcomes for treatment of diabetic macular
      edema with ranibizumab are excellent, but many patients require frequent
      injections to optimally control edema and maximize vision. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier:NCT00407381

PMID- 23544202
TI  - Reply to J. Zhang et al.

PMID- 23544203
TI  - The Detection of Motion by Blind Subjects With the Epiretinal 60-Electrode (Argus
      II) Retinal Prosthesis.
AB  - OBJECTIVE: To investigate the ability of 28 blind subjects implanted with a 60
      electrode Argus II (Second Sight Medical Products Inc) retinal prosthesis system
      to detect the direction of a moving object. METHODS: Blind subjects (bare light
      perception or worse in both eyes) with retinitis pigmentosa were implanted with
      the Argus II prosthesis as part of a phase 1/2 feasibility study at multiple
      clinical sites worldwide. The experiment measured their ability to detect the
      direction of motion of a high-contrast moving bar on a flatscreen monitor in 3
      conditions: with the prosthesis system on and a 1-to-1 mapping of spatial
      information, with the system off, and with the system on but with randomly
      scrambled spatial information. RESULTS: Fifteen subjects (54%) were able to
      perform the task significantly better with their prosthesis system than they were
      with their residual vision, 2 subjects had significantly better performance with
      their residual vision, and no difference was found for 11 subjects. Of the 15
      better-performing subjects, 11 were available for follow-up testing, and 10 of
      them had significantly better performance with normal rather than with scrambled
      spatial information. CONCLUSIONS: This work demonstrates that blind subjects
      implanted with the Argus II retinal prosthesis were able to perform a motion
      detection task they could not do with their native vision, confirming that
      electrical stimulation of the retina provides spatial information from
      synchronized activation of multiple electrodes. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier:NCT00407602

PMID- 23544204
TI  - Reply to M. Rouanne et al.

PMID- 23544205
TI  - Reply to M.S. Hofman et al.

PMID- 23544207
TI  - Discussing driving concerns with older patients: I. vision care providers'
      attitudes and behaviors.
AB  - OBJECTIVE: To investigate the perspectives of vision care providers (VCPs) on
      inquiring about driving among their older adult patients. METHODS: We surveyed a
      stratified random sample of 500 VCPs, 404 of whom completed the survey (response
      rate, 80.8%), who had been identified using membership lists of the Michigan
      Optometric Association and the Michigan Society of Eye Physicians and Surgeons.
      The survey assessed VCPs' attitudes and behaviors in addressing driving concerns
      with older patients. Ordinal logistic regression analyses were performed to
      identify associations between provider or practice characteristics and survey
      responses. RESULTS: More than 80% of VCPs are confident in their ability to
      determine whether their patients' vision is adequate for safe driving. The VCPs
      cite liability risk (for reporting [24.2%] and for not reporting [43.6%]) as a
      barrier to reporting unsafe drivers. Almost two-thirds report routinely inquiring
      about their older patients' driving, and 86.3% consider that counseling patients
      about driving is their responsibility. Almost 60% (57.2%) worry that reporting
      patients negatively influences the physician-patient relationship, and 43.1%
      consider that reporting is a breach of physician-patient confidentiality.
      Attitudes and behaviors in discussing driving varied by VCP characteristics,
      particularly provider type. More than one-third of VCPs (35.6%) report sometimes,
      often, or always communicating concerns about patients' driving to their primary
      care physician. Resources endorsed by VCPs as helpful or very helpful include
      driving assessment guidelines (80.5%), clinical screening instruments (70.1%),
      and patient self-assessment tools (59.9%). CONCLUSION: While VCPs view that
      advising patients about driving is an important responsibility, further attention
      should be given to addressing barriers, providing resources, and devising
      communication strategies between VCPs and other members of the health care team.

PMID- 23544206
TI  - A novel rodent model of posterior ischemic optic neuropathy.
AB  - OBJECTIVES: To develop a reliable, reproducible rat model of posterior ischemic
      optic neuropathy (PION) and study the cellular responses in the optic nerve and
      retina. METHODS: Posterior ischemic optic neuropathy was induced in adult rats by
      photochemically induced ischemia. Retinal and optic nerve vasculature was
      examined by fluorescein isothiocyanate-dextran extravasation. Tissue sectioning
      and immunohistochemistry were used to investigate the pathologic changes. Retinal
      ganglion cell survival at different times after PION induction, with or without
      neurotrophic application, was quantified by fluorogold retrograde labeling.
      RESULTS: Optic nerve injury was confirmed after PION induction, including local
      vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining
      data revealed microglial activation and focal loss of astrocytes, with adjacent
      astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was
      observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared
      with a sham control group. Experimental treatment by brain-derived neurotrophic
      factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell
      loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion
      cells were saved by the application of neurotrophic factors. CONCLUSIONS: Rat
      PION created by photochemically induced ischemia is a reproducible and reliable
      animal model for mimicking the key features of human PION. CLINICAL RELEVANCE:
      The correspondence between the features of this rat PION model to those of human
      PION makes it an ideal model to study the pathophysiologic course of the disease,
      most of which remains to be elucidated. Furthermore, it provides an optimal model
      for testing therapeutic approaches for optic neuropathies.

PMID- 23544209
TI  - [Not Available].

PMID- 23544208
TI  - Discussing driving concerns with older patients II. vision care providers'
      approaches to assessment.
AB  - OBJECTIVES: To characterize situations that prompt vision care providers (VCPs)
      to ask about their older patients' driving, the types of information they
      consider, and the factors that influence these inquiries. METHODS: A survey was
      conducted among a random sample of 500 VCPs who were active members of their
      Michigan professional organizations and had patients 65 years or older in their
      practice. Factors associated with the survey responses were identified using
      ordinal logistic regression analyses. RESULTS: Survey results were obtained from
      404 respondents (80.8%). Common situations that prompted VCPs to ask patients
      about driving included poor visual function, inquiries from the patient or
      family, and requests from the state. Visual acuity and peripheral vision testing
      were frequently relied on (performed always or often by >80% of VCPs), but other
      ocular test results and nonocular information were infrequently obtained.
      Questioning about night driving, reading road signs, and experiencing glare were
      frequent, but inquiries about driving tasks (eg, making left turns) were
      infrequent. The likelihood of asking about specific driving tasks was
      significantly greater with more time in practice and with a higher percentage of
      older patients in their practice, and the likelihood was significantly less for
      ophthalmologist specialists vs optometrists. CONCLUSIONS: Vision care providers
      are often placed in a primary role of advising older patients about their ability
      to drive safely or legally. The most frequent tests they use fail to capture the
      complexities of visual function that contribute to safe driving. The driving
      tasks about which they usually inquire include some, but not all, tasks commonly
      associated with crash risk. Educating VCPs on useful resources, tests, and
      questions is needed.

PMID- 23544210
TI  - Retraction notice to Desalted deep-sea water improves cognitive function in mice
      by increasing the production of insulin-like growth factor-I in the hippocampus.

PMID- 23544211
TI  - [Cronkhite-Canada syndrome].

PMID- 23544213
TI  - [The "appropriate reimbursement" - an illusion!].

PMID- 23544214
TI  - [How can a gastroenterologist also become a proctologist?].

PMID- 23544215
TI  - Tzu-Ching (Teddy) Wu.

PMID- 23544212
TI  - Changes in sexual activity and risk behaviors among PLWHA initiating ART in rural
      district hospitals in Cameroon -- data from the STRATALL ANRS 12110/ESTHER trial.
AB  - The continued scaling-up of antiretroviral therapy (ART) in Sub-Saharan Africa
      provides an opportunity to further study its impact on sexual behaviors among
      people living with HIV/AIDS (PLWHA). We explored time trend and correlates of
      sexual activity among PLWHA initiating ART in Cameroon and compared sexual risk
      behaviors between patients sexually active before and after initiating ART and
      those resuming sexual activity after ART initiation. Analyses were based on
      longitudinal data collected within the randomized trial (n=459) conducted in nine
      rural district hospitals in Cameroon. Sexual activity was defined as reporting at
      least one sexual partner during the previous 3 months. Inconsistent condom use
      (ICU) was defined as reporting to have "never," "sometimes," or "nearly always"
      used condoms at least once with a partner(s) either HIV-negative or of unknown
      HIV status during the same period. Mc Nemar tests were used to assess time trend,
      while mixed-effect logistic regressions were conducted to analyze the effect of
      time since ART initiation on sexual activity. The proportion of sexually active
      patients significantly increased over time: from 31.8% at baseline to 40.2 and
      47.1% after 6 and 12 months of ART, respectively (p=0.001), to 55.9% after 24
      months (p=0.02). After adjustment for behavioral and psychosocial factors, time
      since ART initiation was independently associated with reporting sexual activity
      (AOR [95% CI]=1.30 [1.17-1.46] per 6-month increase, p=0.001). ICU was more
      frequent among patients sexually active both before and after ART initiation than
      among those who resumed sexual activity after ART initiation (82 vs. 59%,
      p<B0.001). To conclude, while ART initiation fosters resumption of sexual
      activity in patients who are inactive before starting treatment; unsafe sexual
      behaviors remain less frequent in this population than in patients who are
      already sexually active before starting ART. Risk reduction programs should be
      reinforced among PLWHA in the context of ART scaling-up.

PMID- 23544216
TI  - What's new in governance for conscious sedation in dental practice.

PMID- 23544217
TI  - Buffered local anaesthetics: the importance of pH and CO2.

PMID- 23544218
TI  - The use of intravenous midazolam and ketamine in paediatric dental sedation.
AB  - In the UK, Dental General Anaesthesia (DGA) was removed from primary care at the
      end of 2001. Since then anxious and 'difficult' paediatric dental patients have
      been treated using local anaesthesia with or without conscious sedation. Evidence
      has been lacking as to the safety and efficacy of paediatric dental sedation in
      primary care. Various centres have presented evidence of good clinical practice
      when anaesthetist-led. This study describes an audit of 500 children treated
      using intravenous midazolam and ketamine, by an operator-sedationist in a primary
      care setting.

PMID- 23544219
TI  - Intravenous ketamine and propofol in paediatric dental sedation: safe and
      effective?

PMID- 23544220
TI  - A retrospective audit to evaluate the effect of the change in midazolam
      concentration from 10 mg/5 ml to 5 mg/5 ml ampoules on midazolam doses given to
      sedation patients following the rapid response report (RRR).
AB  - The technique of intravenous sedation with a benzodiazepine is a well documented
      and successful method for reducing fear and anxiety in many patients who regard
      dental treatment as challenging and potentially painful. One of the most
      important factors to achieving a well sedated patient is ensuring the dose of the
      drug given is titrated to the individual patient. Five years ago, a Rapid
      Response Report issued by the National Patient Safety Agency changed the
      concentration of midazolam within a 5 ml ampoule from 10 mg/5 ml to 5 mg/5 ml. A
      retrospective audit of 300 patients undergoing oral surgery treatment under
      intravenous midazolam sedation at Birmingham Dental Hospital was carried out over
      a 6-month period to assess whether this difference in midazolam concentration had
      any influence on the average dose of midazolam given to these patients. STUDY
      GROUP: The midazolam doses given by five clinicians were audited both before and
      after the concentration change. RESULTS: the mean midazolam dose that was
      administered by three clinicians decreased following the change in concentration.
      In addition, the number of patients given greater than 5 mg midazolam following
      the change decreased with all five clinicians. CONCLUSIONS: The change in
      midazolam concentration from 10 mg/5 ml to 5 mg/5 ml ampoules has resulted in the
      overall average dose of midazolam given by five clinicians at Birmingham Dental
      Hospital to decrease.

PMID- 23544221
TI  - An audit of the sedation activity of participants following their attendance on
      SAAD conscious sedation courses.
AB  - The aim of this study was to analyse the results of a questionnaire given
      directly to participants of SAAD courses in 2011, and posted to previous
      participants, on their own use of conscious sedation. Apart from general
      interest, such data will help the SAAD Faculty to tailor the courses in future
      better to meet the needs of participants by providing insights into the attitudes
      and level of experience in sedation of course participants. Questionnaires were
      distributed to participants on all the 2011 SAAD courses and to all members of
      the dental team. In addition, the same questionnaire was posted to dentists who
      had attended courses in 2010 and 2007. In total 71% of the 157 dentists who
      completed questionnaires were providing conscious sedation in their practices.
      The most common technique used was intravenous sedation. Only 3% carried out any
      advanced techniques. 14% (n = 81) of dentists who had completed a SAAD course
      previously did not go on to use conscious sedation, and possible reasons for this
      are discussed. Participants' overall confidence in specific areas of sedation
      training were rated from 'good' to 'excellent' after completion of a SAAD course.
      Participants completing SAAD courses believe they have gained in confidence and
      in knowledge, and obtained the skills required to provide conscious sedation
      although some identify barriers which prevent them from putting these new skills
      into practice.

PMID- 23544222
TI  - Sedation of children--perspectives across hospital specialties.

PMID- 23544223
TI  - The role of dental therapists in pharmacological and non-pharmacological
      treatment of anxious and phobic patients.
AB  - Dental Therapists are in a prime position to be involved with the management of
      anxious and phobic patients. They earn less than dentists and are therefore a
      more cost-effective way of providing specialised care for anxious patients.
      Dental Therapists can spend more time educating and acclimatising these patients,
      do most if not all of the patient's treatment, only referring back to the dentist
      for RCT, crown/bridgework/dentures and permanent extractions. Ultimately this
      means that the patient receives high quality continuity of care. Treating anxious
      and phobic patients is time-consuming but ultimately very rewarding. If handled
      correctly and sensitively the anxious and phobic patient will not always be
      anxious or phobic, in the same way that children won't always be children. Dental
      Therapists can now extend their duties to include Relative Analgesia. This should
      enhance their employability and role within the dental team especially in the
      management of anxious and phobic patients. Employing a therapist with a toolbox
      of techniques at their disposal can be seen as part of a long-term practice plan
      to ensure that anxious and phobic patients become rehabilitated, happy, compliant
      and loyal to the practice! In fact .... the sort of patients every dentist really
      wants to see.

PMID- 23544224
TI  - The advantages and limitations of the analgesics available for control of
      postoperative pain after a dental procedure.

PMID- 23544225
TI  - Distraction techniques for anxious dental patients an arising field in analgesia
      for modern dentistry.

PMID- 23544226
TI  - Sedation scales and measures--a literature review.
AB  - The monitoring and assessment of the degree of conscious sedation experienced by
      patients is important for both clinical practice and in research. Whereas
      clinical monitoring remains the gold standard for safety in patient care,
      numerous measures are available to supplement this and to provide quantitative
      data on level of sedation. This manuscript provides an overview of existing
      measures of the degree of sedation. Scales that have been used in published
      research were identified from a search of Medline and Google Scholar, and for
      each scale we identified the characteristics of the scale and degree to which the
      reliability and validity of the scale had been measured.

PMID- 23544227
TI  - Reflections on six years as SAAD visiting professor.

PMID- 23544228
TI  - Advanced conscious sedation techniques for adult patients: a participant's
      perspective.

PMID- 23544229
TI  - DSTG Annual Symposium, 22nd May 2012, St Paul's Sheffield.

PMID- 23544230
TI  - Interview with Carole Boyle president of SAAD. Interview by Francis Collier.

PMID- 23544231
TI  - Paul Howlett. New SAAD Trustee.

PMID- 23544232
TI  - Sadie Hughes. New SAAD Trustee.

PMID- 23544233
TI  - Supersized storm. EMS crews faced unprecedented challenges responding to
      Hurricane Sandy.

PMID- 23544235
TI  - Annals hands over.

PMID- 23544234
TI  - [Autism spectrum disorders. How to better recognize?].

PMID- 23544236
TI  - Recommended composition of influenza virus vaccines for use in the 2013-2014
      northern hemisphere influenza season.

PMID- 23544237
TI  - Global report on Fukushima nuclear accident details health risks.

PMID- 23544238
TI  - Antigenic and genetic characteristics of zoonotic influenza viruses and
      development of candidate vaccine viruses for pandemic preparedness.

PMID- 23544240
TI  - Monthly report on dracunculiasis cases, January 2013 - first month with zero
      cases.

PMID- 23544239
TI  - Fact sheet on pneumonia.

PMID- 23544241
TI  - Meningococcal disease in countries of the African meningitis belt, 2012 -
      emerging needs and future perspectives.

PMID- 23544242
TI  - In reply.

PMID- 23544243
TI  - [Interview -- medical guidelines can not and must not replace the intuition of
      the physician].

PMID- 23544244
TI  - [Achilles tendinopathy - flexor hallucis-longus-transfer as therapy].

PMID- 23544245
TI  - [Osteoporosis - bisphosphonates increase atypical femur fractures!].

PMID- 23544246
TI  - [Knee and hip arthroplasty - influence on service life of various comorbidities].

PMID- 23544247
TI  - [Meniscus repair - technology does not matter].

PMID- 23544248
TI  - Biomarker agreement entered into by Verastem and Laboratory Corporation of
      America(r) Holdings.

PMID- 23544249
TI  - MacroGenics and Gilead Sciences to form new antibody alliance.

PMID- 23544250
TI  - Increased accessibility of next-generation sequencing?

PMID- 23544251
TI  - Launch of a US$5 million Parkinson's Disease Biomarkers Program in the USA.

PMID- 23544252
TI  - WILEX AG strikes deal with GeneDiagnostics over the serum HER-/neu ELISA test.

PMID- 23544263
TI  - Gastric cancer with minimal peritoneal metastasis: is this a sign to give up or
      to treat more aggressively?
AB  - Peritoneal metastasis from gastric cancer is often undetectable by routine
      imaging studies. Even a microscopic metastasis detected only by cytologic
      examination of the peritoneal washes denotes a dismal prognosis, and surgery is
      ruled out as futile for patients who turn out to be cytology-positive by staging
      laparoscopy. On the other hand, recent developments in cancer chemotherapy have
      improved the outcome of the cytology-positive population to the point where a
      certain proportion of these patients survive for 5 years through a
      straightforward strategy of radical surgery followed by chemotherapy. Thus, there
      is certainly a role for surgeons in patients with minimal peritoneal metastasis,
      both in clinical practice and in clinical trials where multimodal treatment
      strategies including surgery are to be explored. Even in this category of
      patients, surgery in combination with various types of chemotherapy remains the
      only hope for a cure.

PMID- 23544265
TI  - The regulation of sleep and wakefulness by the hypothalamic neuropeptide
      orexin/hypocretin.
AB  - Orexins, also known as hypocretins, are neuropeptides that are exclusively
      expressed by neurons in the lateral hypothalamic area. Although originally
      recognized as regulators of feeding behavior, orexins are now mainly regarded as
      key modulators of the sleep/wakefulness cycle. In addition, anatomical studies of
      neural networks and analyses of transgenic mice have revealed integrated roles
      for orexin neurons in the coordination of emotion, energy homeostasis, and the
      reward system. A functional link between the limbic system and orexin neurons may
      be important for increasing vigilance in response to emotional stimuli. These
      findings suggest that orexin neurons relay information about an organism's
      environment to maintain the proper amount of sleep and wakefulness in animals.

PMID- 23544264
TI  - What happens in the brain of schizophrenia patients?: an investigation from the
      viewpoint of neuropathology.
AB  - Studies that seek to determine the etiology of schizophrenia through pathological
      images and morphological abnormalities of the brain have been conducted since the
      era of E. Kraepelin, and pioneers in neuropathology such as A. Alzheimer have
      also eagerly pursued such studies. However, there have been no disease-specific
      findings, and there was a brief era in which it was said that "schizophrenia is
      the graveyard of neuropathologists." However, since the 1980s, neuroimaging
      studies with CT and MRI etc., have been used in many reports of cases of
      schizophrenia with abnormal brain morphology, thus generating renewed interest in
      developments within brain tissue and leading to new neuropathological studies.
      There are now many reports in which, in addition to morphological observations,
      cell distribution and the like are image-processed and statistically processed
      through computers. Due to methodological problems in making progress in the field
      of cerebral pathology, we have not yet been able to observe disease-specific
      findings, although there are several findings with high certainty. However, the
      neurodevelopmental hypothesis has been supported as being able to reasonably
      explain the accumulated findings of previous studies. At the same time, results
      of recent molecular-biological studies have revealed the risk genes for this
      disease, and because many of those genes are associated with functions related to
      nerve differentiation, development, and plasticity, there is growing interest in
      their correlations with cerebral pathology. We are now on the verge of uncovering
      the etiology of this disease by integrating cerebral neuroimaging, molecular
      genetics, and cerebral neuropathology. In that sense, neuropathological studies
      of this disease from new viewpoints have become essential.

PMID- 23544266
TI  - Cerebral hemorrhage and cerebral infarction in 30 cases of adult moyamoya
      disease: comparison between conservative therapy and superficial temporal artery
      middle cerebral artery anastomosis.
AB  - To clarify the effect of surgery on the prevention cerebral hemorrhage in adult
      moyamoya disease, we compared postoperative courses between superficial temporal
      artery-middle cerebral artery (STA-MCA) anastomosis and conservative therapy. The
      study subjects were 30 adults with moyamoya disease. Unilateral STA-MCA
      anastomosis was conducted in 7 of these 30 cases, and bilateral STA-MCA
      anastomosis was conducted in 8 of these 30 cases. Therefore, anastomosis was
      performed in a total of 23 sides. The postoperative clinical course was observed
      for more than 5 years after the STA-MCA anastomosis. Cerebral hemorrhage occurred
      after operation in 2 sides (8.7%) among the 23 sides that received STA-MCA
      anastomosis. On the contrary, hemorrhage occurred during conservative therapy in
      5 sides (13.5%) among 37 non-operation sides (no significance in chi2 test).
      Cerebral infarction occurred in 3 sides (13%) among 23 sides treated with STA-MCA
      anastomosis. However, the infarction occurred in 2 sides (5.4%) among the 37 non
      operation sides (no significance in chi2 test). Cerebral hemorrhage tended to
      occur less frequently after STA-MCA anastomosis, and bypass surgery was suggested
      to have some beneficial effect in preventing cerebral hemorrhage in adult
      moyamoya disease. However, it was revealed that STA-MCA anastomosis exacerbated
      the brain ischemia. Therefore, strict management is mandatory in the
      perioperative period.

PMID- 23544267
TI  - Atherothrombotic lesion of the middle cerebral artery: report of 21 cases with
      stenotic and obstructive lesions.
AB  - This was a retrospective analysis of 12 consecutive cases of middle cerebral
      artery stenosis and 9 consecutive cases of middle cerebral artery occlusion that
      presented to our hospital with acute cerebral ischemia. The degree and area of
      the cerebral infarctions were assessed with the Alberta Stroke Program Early CT
      Score (ASPECTS) and ASPECTS-DWI (APSECTS with assessment of white matter lesion
      using diffusion-weighted image). As for cerebral infarctions in the region of the
      perforating artery, lesions that were more than 20 mm long in the caudal-cranial
      direction were diagnosed as branch atheromatous disease (BAD). Activities of
      daily living (ADL) were poorer in the cases with lower ASPECTS and ASPECTS-DWI.
      ADL tended to be worse in cases with BAD than in those without. The prognosis was
      significantly poorer in the group with ASPECTS< or =7 points. ASPECTS tended to
      be lower in cases with BAD than in those without. ADL, ASPECTS and the presence
      of BAD were not significantly different between the stenosis and obstruction
      groups. In summary, the neurological prognosis was dependent on the extent of the
      cerebral infarction and was related to BAD to some extent. These findings will be
      important when considering medical treatment at the outpatient clinic setting.

PMID- 23544268
TI  - Impact of back muscle strength and aging on locomotive syndrome in community
      living Japanese women.
AB  - The Japanese Orthopaedic Association has proposed the term locomotive syndrome
      (LS) to designate a condition of individuals in high-risk groups with
      musculoskeletal disease who are highly likely to require nursing care. This study
      investigates the influence of spinal factors on LS in Japanese females. A total
      of 187 women > or =50 years old were enrolled in the study. Those answering yes
      to least one of the 7 categories in the self-assessment checklist for LS were
      defined as having LS. We evaluated lateral lumbar radiographs, sagittal
      parameters, sagittal balance using the spinal inclination angle (SIA) as an
      index, spinal range of motion (ROM) as determined with SpinalMouse, back muscle
      strength (BMS), and body mass index (BMI). Age, BMI, BMS, SIA, sacral slope angle
      (SSA), and lumbar spinal ROM showed significant correlations with LS. Multiple
      logistic regression analysis indicated that an increase in age (OR 1.054, p<0.05)
      and a decrease in BMS (OR 0.968, p<0.01) were significantly associated with LS.
      Age had significant negative correlations with BMS, SSA, thoracic and lumbar
      spinal ROM, and it had positive correlations with BMI, SIA, and lumbar kyphosis.
      BMS had significant negative correlations with age, SIA, thoracic and lumbar
      kyphosis, and it had positive correlations with SSA, lumbar and total spinal ROM.
      An increase in age and a decrease in BMS may be the most important risk factors
      for LS in Japanese women. Back muscle strengthening and spinal ROM exercises
      could be useful for improving the status of an individual suffering from LS.

PMID- 23544269
TI  - Simple and rapid quantitation of 21 bile acids in rat serum and liver by UPLC-MS
      MS: effect of high fat diet on glycine conjugates of rat bile acids.
AB  - In this report, we present a simple and rapid method for analysis of 21 kinds of
      bile acids and the conjugates in rat serum and liver samples by ultra-performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) in the negative
      ionization mode, using cholic-2, 2, 4, 4-d4 acid as internal standard. After
      liquid-liguid extraction from serum and liver samples, specimens were analyzed by
      UPLC equipped with an Acquity TQD tandem quadrupole mass spectrometer. All of the
      21 bile acids were sufficiently separated within 5 min. For most bile acids,
      calibration curves showed good linearities in the range of 0.25 to 5000 ng/mL for
      serum samples, 2.5 ng/g to 50 microg/g for liver samples. The limits of detection
      (LOD) were estimated to be less than 0.25 to 7.5 ng/mL in serum, less than 2.5 to
      10 ng/g in liver samples. The present method was validated with respect to
      repeatability; the coefficient of variation (CV) values were less than 26.7% in
      the serum and 25.9% in the liver. In the animal study, we compared 21 bile acids
      in the serum and liver samples of the stroke-prone spontaneously hypertensive
      (SHRSP) rats fed with control (SP) diet or high-fat and high-cholesterol
      containing (HFC) diet. By feeding with HFC diet, the glycine conjugates of some
      bile acids significantly increased and the taurine conjugate of ulsodeoxicolate
      (TUDC) decreased in serum and liver samples. Our results suggest that the change
      of bile acid profiles could be applied for the diagnosis of non-alcoholic fatty
      liver disease (NAFLD).

PMID- 23544270
TI  - DPP4 genetic variants influence baseline prostate-specific antigen levels: the J
      MICC study.
AB  - Prostate specific antigen (PSA) testing plays a major role in prostate cancer
      screening; however, the low positive predictive value of PSA testing leads to
      many unnecessary biopsies. Genetic background is one of factors that could cause
      it. That's why an association between genetic background and PSA levels should be
      elucidated. This study aimed to investigate whether DPP4 genetic variants are
      associated with baseline PSA levels. A cross-sectional study was performed on
      2,074 Japanese men aged between 35 and 69 in the Shizuoka area from the Japan
      Multi-institutional Collaborative Cohort (J-MICC) Study. Three DPP4 tagging
      single nucleotide polymorphisms (SNPs) were selected for genotyping: rs3788979
      (A/G), rs7608798 (T/C), and rs2268889 (A/G). Higher mean serum PSA levels were
      significantly associated with an increase in the number of the rs7608798 C allele
      (p for trend = 0.02). A stratified analysis by age groups demonstrated that PSA
      levels had positive significant trends with the numbers of the minor alleles of
      rs3788979 or rs7608798 in the oldest group (men aged between 60 and 69) (p for
      trend=0.004 for rs3788979 and p for trend=0.001 for rs7608798). Haplotype
      analysis showed that the C-A (rs7608798-rs2268889) haplotype was significantly
      associated with increased PSA levels (p=0.006), compared with the most common
      haplotype, T-A. In summary, our study suggests that DPP4 genetic variants
      influence baseline PSA levels, especially in men aged between 60 and 69.

PMID- 23544271
TI  - Glucocorticoid-induced hypertension and cardiac injury: effects of
      mineralocorticoid and glucocorticoid receptor antagonism.
AB  - Glucocorticoids are widely administered for the treatment of various disorders,
      although their long-term use results in adverse effects associated with
      glucocorticoid excess. We investigated the pathophysiological roles of
      glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the
      cardiac changes induced by exogenous corticosterone in rats. Corticosterone or
      vehicle was injected twice daily in rats from 8 to 12 weeks of age. The effects
      of the GR antagonist RU486, the MR antagonist spironolactone, or both agents on
      corticosterone action were also determined. Corticosterone induced hypertension,
      left ventricular (LV) fibrosis, and LV diastolic dysfunction. Neither RU486 nor
      spironolactone affected corticosterone-induced hypertension, whereas
      spironolactone, but not RU486, attenuated the effects of corticosterone on LV
      fibrosis and diastolic function. Corticosterone also increased cardiac oxidative
      stress and inflammation in a manner sensitive to spironolactone but not to RU486.
      The corticosterone-induced LV atrophy was not affected by either RU486 or
      spironolactone. Our results implicate MRs in the cardiac fibrosis and diastolic
      dysfunction, but not MRs or GRs in the cardiac atrophy, induced by
      corticosterone. Neither MRs nor GRs appear to contribute to corticosterone
      induced hypertension.

PMID- 23544272
TI  - No association between MTHFR C677T and serum uric acid levels among Japanese with
      ABCG2 126QQ and SLC22A12 258WW.
AB  - Several genome-wide association studies (GWAS) have revealed that single
      nucleotide polymorphisms (SNPs) of ABCG2 and SLC22A12 were strongly associated
      with serum uric acid (SUA), but those of methylene tetrahydrofolate reductase
      (MTHFR) were not. However, there were several studies indicating the association
      with MTHFR C677T polymorphism. This study examined the association with the
      polymorphism, taking into account the genotypes of ABCG2 Q126X and SLC22A12
      W258X. Subjects were 5,028 health checkup examinees of Seirei Preventive Health
      Care Center (3,416 males and 1,612 females) aged 35 to 69 years, who participated
      in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).
      Hyperuricemia was defined as SUA equal to 7 mg/dL or over. The genotype frequency
      was 35.9% for CC, 48.1% for CT, and 16.0% for TT, being in Hardy-Weinberg
      equilibrium (p=0.90). Among 4,425 participants with ABCG2 126QQ and SLC22A12
      258WW who were not under medication for hyperuricemia, the mean SUA was 5.6
      mg/dL, 5.6 mg/dL, and 5.7 mg/dL, respectively. When 114 participants with ABCG2
      126QQ and SLC22A12 258WW under medication for hyperuricemia were included in
      hyperuricemia cases, the sex-age adjusted odds ratio (OR) of hyperuricemia was
      not significant; OR=1.00 (95% confidence interval, 0.89-1.24) for CT genotype and
      OR=0.98 (0.84-1.32) for TT genotype, relative to CC genotype. The present study
      indicated no association between SUA and MTHFR C677T genotype, after the
      influences of ABCG2 Q126X and SLC22A12 W258X were removed.

PMID- 23544273
TI  - Surface markers and gene expression to characterize the differentiation of
      monolayer expanded human articular chondrocytes.
AB  - Autologous chondrocyte implantation (ACI) is a method of cartilage repair. To
      improve the quality of regenerated tissue by ACI, it is essential to identify
      surface marker expression correlated with the differentiation status of monolayer
      expanded human articular chondrocytes and to define the index for discriminating
      dedifferentiated cells from monolayer expanded human articular chondrocytes.
      Normal human articular chondrocytes were cultured in monolayer until passage 4.
      At each passage, mRNA expression of collagen type I, II, and X and aggrecan was
      analyzed by real-time quantitative PCR, and the surface marker expression of
      CD14, CD26, CD44, CD49a, CD49c, CD54, and CD151 was analyzed by fluorescence
      activated cell sorting (FACS). The ratios of mRNA levels of collagen type II to I
      (Col II/Col I) represented the differentiation status of chondrocytes more
      appropriately during monolayer culture. The surface marker expression of CD44,
      CD49c, and CD151 was upregulated according to the dedifferentiation status,
      whereas that of CD14, CD49a, and CD54 was downregulated. The most appropriate
      combination of the ratio of Col II/Col I was CD54 and CD44. Cell sorting was
      performed using a magnetic cell sorting system (MACS) according to CD54 and CD44,
      and real-time quantitative PCR was performed for the cell subpopulations before
      and after cell sorting. The expression of collagen type II and aggrecan of the
      chondrocytes after MACS was higher than that before sorting, but not
      significantly. The mean fluorescence intensity (MFI) ratio of CD54 to CD44 could
      be an adequate candidate as the index of the differentiation status.

PMID- 23544274
TI  - Reappraisal of importance of the left internal mammary artery to the left
      anterior descending artery in improving mid-term outcome in patients with severe
      left ventricular dysfunction.
AB  - We sought to investigate the effects of the left internal mammary artery
      anastomosed to the left anterior descending artery for improving mid-term outcome
      in patients with severe left ventricular dysfunction. Twenty consecutive coronary
      artery bypass grafts performed by a single surgeon for less than 35% ejection
      fraction patients were reviewed retrospectively from April 2000 to November 2008.
      There was one perioperative death (5.0% mortality). The mean survival was 55
      months with an actual 5-year survival rate of 75%. Echocardiography showed the
      ejection fraction improved to 10.7 +/- 0.32% (p < 0.01). The strongest
      correlation was observed between both the flow and the pulsatile index of the
      left internal mammary artery measured intraoperatively by transit time flow meter
      and the postoperative ejection fraction improvement (R2=0.737 and 0.639,
      respectively). We reappraised the mid-term beneficial effects of the internal
      mammary artery anastomosed to the left anterior descending artery in patients
      with severe left ventricular function.

PMID- 23544275
TI  - Advantage of a more central incision onto left atrium by using ultrasonic
      scalpel.
AB  - Exposure of the mitral valve is of critical importance in mitral valve surgery.
      The mitral valve is located near the interatrial groove. As we accumulated
      experience and learned from embryology, we found that a more central left
      atriotomy was advantageous, and was made possible by interatrial groove
      dissection using an ultrasonic scalpel. This crucial finding prompted us to
      report the technique.

PMID- 23544276
TI  - A surface-based hemangioma of the radius which posed radiological diagnostic
      difficulties.
AB  - Surface-based bone hemangiomas are uncommon, mostly occurring in long bones of
      the lower extremities. Radiographic surface-based bone hemangioma images may
      present various features that provide a diagnostic challenge. We report a case of
      surface-based hemangioma of the radius that posed radiological diagnostic
      difficulties. The tumor size was small and the cortical reaction was subtle. MRI
      findings were nonspecific and angiography was useful in the assessment of painful
      but less obvious surface-based bone hemangioma. The patient's pain improved
      following surgery and no tumor recurrence was observed at 3 years after surgery.

PMID- 23544277
TI  - Stabilizing incomplete reduction of the radial head using a hinged splint:
      conservative treatment for a Monteggia equivalent lesion.
AB  - Radial head dislocation associated with plastic bowing of the ulna is classified
      as a Monteggia equivalent lesion. This injury in children can be treated by
      closed reduction, but manipulative reduction may not completely correct plastic
      bowing of the ulna. We encountered two cases of incomplete reduction in which the
      radial head was reduced in a supination position, but redislocated during
      rotation from neutral to a pronation position. The patients were treated
      conservatively using an adjustable hinged elbow splint. Plain radiography at 6
      weeks after incomplete closed reduction showed that the radial head was reduced
      in all positions from supination to pronation; thus, both patients had good
      outcomes. Our method is non-invasive and may be an option for treatment of
      incomplete reduction of radial head dislocation with acute plastic bowing of the
      ulna.

PMID- 23544278
TI  - Selective IgA deficiency mimicking Churg-Strauss syndrome and hypereosinophilic
      syndrome: a case report.
AB  - Selective IgA deficiency (SIgAD) is the most common type of primary
      immunoglobulin deficiency. Most individuals with SIgAD are asymptomatic. However,
      some patients are associated with allergic and autoimmune disease. SIgAD is
      included in the list of differential diagnoses of eosinophilia. We experienced a
      patient who initially presented with abdominal pain and eosinophilia. A >1-year
      follow-up revealed SIgAD, and we had difficulty differentiating it from Churg
      Strauss syndrome (CSS) or hypereosinophilic syndrome (HES). A 66-year-old
      Japanese male presented with a history of recurrent abdominal pain. A diagnostic
      work-up revealed eosinophilia, eosinophilic gastritis, eosinophilic pneumonia,
      and SIgAD over 1 year of clinical observation. He also suffered from asthma and
      sinusitis. Anti-neutrophil cytoplasmic antibody was negative and vasculitis was
      not detected in the obtained tissue specimens of stomach, lung, nose and skin.
      The patient showed no evidence of drug ingestion, parasitic infections, or
      malignant neoplasms. Although we cannot rule out prevasculitic CSS and idiopathic
      HES, the whole clinical picture in this patient can be explained most
      consistently by SIgAD.

PMID- 23544279
TI  - Impalement injury to the left buttock with massive bleeding: a case report.
AB  - A 67-year-old man fell from the second floor of his home and was impaled on an
      iron pipe used for a garden stake. The pipe was 2 cm in diameter and had entered
      his left buttock to his anus. A plain abdominal X-ray film showed that the tip of
      the pipe was located in front of the 4th lumbar vertebra, so the penetration
      distance was 30 cm. An emergency operation was performed for hemorrhagic shock.
      Laparotomy revealed massive intra-abdominal bleeding, injuries of the sigmoid and
      transverse mesocolon, superior rectal artery, and the first part of the duodenum.
      Because of suspected lower rectal injury, division of the upper rectum, closure
      of the rectal stump, and sigmoidostomy were performed. Gauze packing into the
      pelvic cavity was performed for uncontrollable bleeding. All the gauze was
      postoperatively removed from the drain wound without laparotomy. Six months after
      the operation, he underwent a second operation including anastomosis of the
      descending colon and lower rectum, which allowed him to live a normal daily life.

PMID- 23544280
TI  - New hypothesis on the origin of metastases.
AB  - A new hypothesis for the origin of metastases is presented. It assumes that a
      cancer-transformed gene in a primary tumour is incorporated in its identical form
      via a virus-vector function into biologically potent recipient cells in other
      organs, such as stem cells, multipotent cells or cells in an early phase of
      division. The origin of metastases may thus possibly occur via a genetic pathway.

PMID- 23544281
TI  - Coverage is not enough: we need a transformation of the delivery of health care!

PMID- 23544282
TI  - Your license on the line: what you need to know about the disciplinary process.

PMID- 23544283
TI  - Workplace violence protection for healthcare providers needed in Tennessee.

PMID- 23544284
TI  - The triumph of evil.

PMID- 23544285
TI  - Concierge medicine, "keeper of the candles"?

PMID- 23544286
TI  - Drug-dependent at birth: neonatal abstinence syndrome in Tennessee.

PMID- 23544287
TI  - Verifying patient medical insurance eligibility--how did it get so complicated?

PMID- 23544288
TI  - Knowledge of addiction medicine among internal medicine residents and medical
      students.
AB  - OBJECTIVES: More than 22 million Americans are living with addiction, including
      nearly seven million who misuse prescription medications. However, most medical
      schools and residency programs provide little to no education addressing alcohol
      and drug addiction. Implementation of a new addiction medicine curriculum at a
      single internal medicine program provided an opportunity for knowledge assessment
      in a select population of health professionals. We hypothesized that knowledge of
      addiction medicine would not differ by training level or geographical location of
      medical school, but that knowledge would improve following a structured
      curriculum. METHODS: Study participants included internal medicine and
      transitional year residents, as well as a group of medical students who were
      enrolled in a single internal medicine program at the time of the didactic
      series. A pre-test was administered prior to a four-week structured curriculum.
      The topics addressed included but were not limited to: 1) an overview of
      addiction, 2) opioids and chronic pain, 3) benzodiazepines and illicit
      stimulants, and 4) alcohol. A panel discussion was convened at the end of the
      fourth session. Following participation in the symposium, participants completed
      an online post-test. ANOVA was used to compare means. Paired t-tests were used to
      compare pre-test and post-test scores. RESULTS: 36 of 44 eligible medical
      students and residents completed the pre-test. Mean pre-test percentage scores
      were 64 percent for fourth year medical students and 62.5 percent for all
      residents. For residents, U.S. medical school trainees answered 65 percent of the
      pre-test questions correctly, versus 58.6 percent correct responses among their
      international medical graduate peers. No inter-group differences were
      statistically significant. Of the 36 participants, 20 completed both pre-tests
      and post-tests. The mean post-test score of 68.75 percent was higher than the
      mean pre-test score of 61.75 percent, p = 0.009. CONCLUSIONS: Knowledge of
      addiction medicine can be improved for medical students and residents in an
      academic medicine department. Significant improvements were observed following
      completion of eight hours of interactive didactics.

PMID- 23544289
TI  - Hemoptysis and respiratory failure following sildenafil use for pulmonary
      hypertension.
AB  - Sildenafil, usually a well-tolerated drug traditionally used for erectile
      dysfunction (ED), was recently approved for pulmonary arterial hypertension. In
      the literature, there are few cases of hemoptysis following sildenafil use for
      ED; however, to our knowledge, we are reporting the first case of hemoptysis
      following sildenafil use for pulmonary hypertension. We are documenting a case of
      a 90-year-old male patient who was admitted to the intensive care unit with
      hemoptysis and respiratory failure two weeks after he was started on sildenafil.

PMID- 23544290
TI  - Pulmonary blastomycosis during pregnancy: case report and review of the
      literature.
AB  - Blastomycosis rarely presents in pregnancy. Pregnancy is a state of partial
      immunodeficiency that predisposes to blastomyces infection, especially in endemic
      areas. Blastomycosis in pregnancy has been reported in a few female patients and
      their offspring. We are reporting a 32-year-old pregnant patient at 34 weeks of
      gestation who presented with a lung mass. The cytopathological exam of the biopsy
      taken by fine needle aspiration showed evidence of Blastomyces organisms. She
      received Liposomal Amphotericin B and was followed closely until delivery. The
      placenta was examined and did not show evidence of infection in the fetus.
      Healthcare professionals in endemic areas such as Tennessee should be aware of
      blastomycosis in pregnancy.

PMID- 23544291
TI  - Tennessee emergency medicine workforce, 2009.
AB  - OBJECTIVE: Describe the characteristics of the Tennessee (TN) Emergency Medicine
      (EM) workforce. METHODS: A cross-sectional mail survey of all non-government
      emergency departments (EDs) in TN was performed between January and April 2009.
      Data collected included: number and residency training of physicians, ED volume,
      employment and type of mid-level providers. Survey datawere compared to recent
      national EM workforce data. Subgroup analysis of rural EDs using Rural-Urban
      Commuting Area Code (RUCA) criteria was conducted. RESULTS: We received responses
      from 50 of the 100 emergency departments surveyed. Roughly half (53 percent) were
      rural, based on RUCA criteria. Mid-level providers worked with physicians in 31
      departments, with physician assistants(PAs) being employed more commonly than
      nurse practitioners(NPs). Paramedics and emergency medical technicians (EMTs)
      were employed less frequently. Most EM residency trained physicians in Tennessee
      are working in EDs with approximately 39,000 annual visits per year or greater.
      Subspecialty physicians such as neurosurgeons, gastroenterologists and
      otorhinolaryngologists are generally not available to rural EDs, except by
      patient transfer, illustrating the marked differences in the work environments.
      CONCLUSION: While there is clearly a need for more emergency medicine residency
      training programs in Tennessee, the need to continue to provide advanced training
      for family medicine residency trained physicians is also clear. Family medicine
      doctors provide most of the rural emergency medicine in Tennessee.

PMID- 23544292
TI  - Why be an alliance member-at-large?

PMID- 23544293
TI  - The scream in medicine.

PMID- 23544294
TI  - Pap smear: what's new?

PMID- 23544295
TI  - Spontaneous pneumomediastinum with subcutaneous emphysema: report of two
      pediatric cases.
AB  - We present two children diagnosed with spontaneous pneumomediastinum. The first
      case is a 9-year-old male who developed neck pain with a history of poorly
      controlled asthma and recently diagnosed right middle lobe pneumonia. The second
      case is a 14-year-old male who developed chest pain with a history of cough and
      congestion for four days. We describe their clinical courses and discuss briefly
      the epidemiology, pathophysiology, diagnosis, and treatment of spontaneous
      pneumomediastinum. Though relatively rare in occurrence, we present these cases
      of spontaneous pneumomediastinum to demonstrate the variation in presentation.

PMID- 23544296
TI  - Ketosis-resistant diabetes: a rare case in unlikely territory.
AB  - BACKGROUND: Ketosis-resistant diabetes is a syndrome that has undergone numerous
      classification schemes in the past. In 1979, the National Diabetes Data Group
      (NDDG) introduced an association of malnutrition and diabetes. In 1985, the World
      Health Organization (WHO) created a new diabetes category called malnutrition
      related diabetes mellitus (MRDM). MRDM consisted of two subclasses:
      fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic
      diabetes (PDPD). Ketosis-resistant diabetes of the young (KRDY) was included in
      the subclass of PDPD. We report a rare case of a 37-year-old Sudanese immigrant
      with ketosis-resistant diabetes. CASE: A previously healthy 37-year-old male
      presented with increased lethargy, polydipsia, polyuria and weight loss for the
      last seven to eight months. The patient had immigrated to the U.S. from his
      native country of Sudan about seven years earlier. He was hemodynamically stable.
      Physical exam was unremarkable with no evidence of retinopathy or neuropathy.
      Initial laboratory findings revealed a random blood sugar of 1,409 mg/dl and
      hemoglobin A1C of 17.8 percent. Urinalysis showed negative proteinuria, positive
      glycosuria, but only trace ketones were detected. Interestingly, the patient's
      serum ketones were negative. Arterial blood gas revealed PH 7.37, PCO2 47, P02
      108 and HCO3 27. Further diagnostic workup revealed C-peptide 0.36, insulin
      antibodies less than 2, glutamic acid decarboxylase (GAD) antibodies less than
      0.5, ICA 512 antibodies 2.9 and negative anti-islet cell antibodies. An abdominal
      ultrasound did not show any evidence of pancreatic calcifications or any
      pathology. Aggressive fluid resuscitation and intravenous insulin was initiated.
      The patient's hospital course was uncomplicated. He responded well to intravenous
      insulin drip and hydration. He was eventually transitioned to subcutaneous
      insulin. He was discharged three days later on a home regimen that included
      Lantus 28 units SQ at night, Novolog 8 units SQ with meals and a sliding scale
      with Novolog as needed. The patient's recent follow-up appointment revealed
      adequate glycemic control with HbA1C level of 7 percent. CONCLUSION: Our patient
      did not meet criteria for either type 1 or type 2 diabetes mellitus. After a
      literature review of atypical etiologies of diabetes and comparing them to our
      patient, we concluded that the most likely diagnosis was KRDY. In light of a high
      influx of refugees and immigrants to the U.S., we should entertain. KRDY and
      other rare causes of diabetes mellitus in patients not satisfying criteria of
      either type 1 or type 2 diabetes.

PMID- 23544297
TI  - Meningioma mimicking Parkinson's disease: a case report and analysis.
AB  - An unusual case of apparent Parkinson's disease caused by a brain tumor
      (meningioma) is presented. The role of brain imaging in the evaluation of a
      patient with Parkinson's symptoms is discussed.

PMID- 23544298
TI  - Recent issues regarding controlled substances.

PMID- 23544299
TI  - The humility of diversification.

PMID- 23544300
TI  - Coping with rhubarb pie.

PMID- 23544301
TI  - South Dakota council on colorectal cancer releases the 2013 colorectal cancer
      monograph.

PMID- 23544302
TI  - DAKOTACARE approves Class C stock redemption and reserve payment.

PMID- 23544303
TI  - [Mechanical ventilation parameters associated to barotrauma in a neonatal
      intensive care unit].
AB  - OBJECTIVE: To identify the parameters of mechanical ventilation related to
      barotrauma and to identify associated diseases. MATERIAL AND METHODS: There was a
      partial retrospective study which included all the files and/or newborns (NB) who
      were in the Neonatal Intensive Care Unit during March 2003 to April 2008 met the
      inclusion criteria. Two groups were conformed, the group A, cases (those with
      barotrauma) and B controls (that did not show it). Area of significance was
      considered when p < 0.05. RESULTS: In multivariate analysis was only significant
      relevance in relation to the ventilatory parameters mean airway pressure (MAP) >
      10 cm H20 on the eighth day, and as confronted all variables including one
      different from the ventilator as arterial blood gases in the multivariate
      analysis also, the oxygenation index (OI) with a value > 10 showed statistical
      significance as it preceded to the barotrauma. The pathology associated with
      barotrauma was patent ductus arteriosus (PDA) hemodynamically significant with p
      < 0.05. CONCLUSIONS: Based on the foregoing its is concluded that when a NB
      patient with mechanical ventilatory support after the first days, to improve lung
      compliance should be going down different ventilatory parameters as soon as
      possible to avoid reaching a MAP > 10 cm H2O above the eighth day of ventilatory
      management, but OI > 10 at any time would be announcing the possibility of
      barotrauma and other side to treat the significant hemodynamically PDA either
      medically or surgically in the shortest time.

PMID- 23544304
TI  - Major craniofacial defects: case series and prenatal diagnosis at the Instituto
      Nacional de Perinatologia, Mexico.
AB  - OBJECTIVE: To describe the prenatal diagnosis, characteristics, development,
      perinatal outcome, and final diagnosis of pregnancies complicated by fetuses with
      major craniofacial defects, at the Instituto Nacional de Perinatologia, Mexico,
      1997-2008. MATERIAL AND METHODS: A retrospective, descriptive study from January
      of 1997 to January 2008, analyzed 152 pregnancies complicated by fetuses with
      major craniofacial defects, diagnosed at the Department of Fetal Medicine of the
      National Institute of Perinatology. Data were obtained from patients clinical
      records. RESULTS: . The mean age was 28 +/- 8 years, with the largest number of
      cases between 20 and 24. The mean gestational age at diagnosis was 27.5 +/- 6.4
      gestational weeks. The average termination of pregnancy was at 35 +/- 5
      gestational weeks. In 43.4% of cases there were no major structural defects
      associated with the facial defect. The most commonly associated structural
      alterations were cerebral, cardiac, and limb abnormalities. Karyotyping was
      performed in only 57 cases, and was abnormal in 25. CONCLUSIONS: Structural
      ultrasound should be performed on all pregnant women between weeks 18 and 24 for
      detection of major craniofacial defects. Where defects are found, a thorough
      review of other structures should be carried out to determine whether the defects
      are syndromic. A systematic and multidisciplinary approach is essential to
      providing the best care and appropriate advice to parents.

PMID- 23544305
TI  - Prenatal prevalence of skeletal dysplasias and a proposal ultrasonographic
      diagnosis approach.
AB  - OBJECTIVE: To determine the prevalence of fetal bone dysplasias diagnosed at the
      Department of Maternal Fetal Medicine (UNIMEF) of the Instituto Nacional de
      Perinatologia (INPer); and to describe the most frequent skeletal dysplasias and
      to propose a diagnostic flow chart. MATERIALS AND METHODS: This is a case series
      study including skeletal dysplasias cases from January 1995 until December 2009
      at the UNIMEF Statistical analysis was performed using SPSS 12 statistical
      software. RESULTS: A total of 81,892 births were registered at the institution
      during the study period. The prevalence of bone dysplasia was 8.1 per 10,000
      births. We used a diagnostic flow chart that was developed at our institution to
      diagnose skeletal dysplasias. Micromelia (n = 40, 59.7%) and both rhizomelia and
      mesomelia (n = 17, 25.3%) were highly prevalent. We found other structural
      anomalies in 40 cases (61.1%), which were associated with different skeletal
      dysplasias; these other anomalies were mainly congenital heart diseases (12
      cases) with a predominance of ventricular septal defects. There was
      polyhydramnios in 43.2% of cases. The mean of the gestational age at diagnosis
      was 24.5 weeks (SD 5.66). The karyotype was obtained in 11.9% (8/67) of cases. A
      total of 7 stillbirths and 11 neonatal deaths were registered, of which only 10
      cases received a necropsy. Births occurred in the third trimester for 88% of
      cases, of which 85% were born via Cesarean section, whereas in the second
      trimester, the vaginal approach was chosen in 100% of cases. CONCLUSIONS: The
      prenatal diagnosis of bone dysplasias is challenging due to the late development
      of the diagnostic features. Nevertheless, using ultrasonography in a systematic
      approach, in conjunction with a multidisciplinary approach, is a key factor in
      the diagnosis of this disease during the fetal period.

PMID- 23544306
TI  - [Reference values for the blood coagulation tests in Mexico: usefulness of the
      pooled plasma from blood donors].
AB  - INTRODUCTION: The blood coagulation system maintains the blood in a liquid state
      and bleeding and thrombosis are the manifestations of its malfunction. Blood
      coagulation laboratory evaluates the physiology of this system. OBJECTIVE: To
      establish both, the reference values for several tests performed at the blood
      coagulation laboratory as well as the utility of the pooled plasma to perform
      these assays. MATERIAL AND: METHODS: In this descriptive, cross-sectional,
      randomized study, we collected plasma from Mexican Mestizos. Each pooled plasma
      was prepared with the plasma from at least 20 blood donors. We performed
      screening and special tests and the Levey-Jennings graphs were built and
      interpreted after each pass. Results of the tests were analyzed and their
      distribution was established using the Kolmogorov-Smirnov test. To establish the
      reference values we used 95% confidence intervals. RESULTS: We collected 72
      pooled plasmas. The distribution for PT, APTT, and TT tests was abnormal.
      Although the PT test showed a bimodal distribution it was normal for factor VII.
      The reference values for the hemostatic, anticoagulant, and fibrinolytic factors
      were different from those suggested by the manufacturers. CONCLUSION: We
      established the reference values for the blood coagulation tests in the adult
      Mexican population. We have shown that the pooled plasma must be used for the
      screening tests. We suggest that each clinical laboratory should establish its
      own reference values (at least for the screening tests). To reach this objective,
      we encourage the use of the pooled plasma.

PMID- 23544307
TI  - Mortality trend by dengue in Mexico 1980 to 2009.
AB  - OBJECTIVE: To describe the mortality of dengue in Mexico during 1980 to 2009.
      MATERIAL AND METHODS: Dengue mortality data for Mexico were obtained from
      Instituto Nacional de Estadistica, Geografia e Informatica. We used standardized
      and non-standardized dengue mortality rates per 1,000,000 people and determined
      the mortality trend. The groups were based on International Classification of
      Diseases coding criteria (ICD-9 E061 and ICD-10 A91X). The results were
      stratified by age groups and the frequencies of dengue deaths were compared using
      relative risk (RR) with its 95% confidence interval. RESULTS: During 1980 to 2009
      in Mexico, 549 deaths due to dengue were reported. We found an important
      variation in the mortality rates during the years studied. We were able to
      identify three periods: 1980 to 1992, 1994 to 2000, and 2001 to 2009. The
      mortality rates found are from 0.88/1,000,000 through 0.00/1,000,000. The average
      mortality rates by decade: 1980 to 1989: 0.53/1,000,000; 1990 to 1999:
      0.06/1,000,000; 2000 to 2009: 0.12/1,000,000. In the analysis of mortality by
      community size during 2000 to 2009, we observed in the small communities with <
      2,499 people, the risk is 1.25 times higher than in those with more than 20,000
      people. CONCLUSIONS: We found, in general, a sustained decline in the number of
      deaths by dengue over the last 30 years in Mexico. However, a slow increase was
      observed since 1994, which may be related to the circulation of DENV2 and DENV3,
      among other factors. We need to strengthen prevention programs in smaller
      communities (< 2,499) where we found a higher risk of mortality due to dengue.

PMID- 23544308
TI  - [Effects of propofol pretreatment on endothelin in oleic acid-induced acute lung
      injury].
AB  - INTRODUCTION: Acute lung injury (ALI) is a pathological condition characterized
      by injury in the alveolar-capillary membrane that triggers local and systemic
      inflammation. Endothelin (ET) is a protein that regulates immune response and
      constricts blood vessels; when it is over-expressed, it may contribute to high
      blood pressure and lung injury. This work tries to determine if propofol may
      decrease hemodynamic, gasometric, microscopic, ET-1 plasmatic concentration, and
      immuno-histochemical alterations in an experimental model of oleic acid-induced
      acute lung injury. MATERIALS AND METHODS. Animals were classified into three
      groups (n = 6): group I was the control group; in group II, there was oleic acid
      induced ALI with no treatment, and group III with propofol pre-treatment and
      oleic acid-induced ALI. RESULTS: All animals survived until the end of the study,
      and 100% of group II and group III developed ALI, with hemodynamic, gasometric
      and gravimetric alterations. However, group III showed less inflammatory
      infiltration and lower ET-1 expression in lung tissue. CONCLUSIONS: Pretreatment
      with propofol in a canine model of OA-induced ALI indicates that the drug has
      anti-inflammatory action, with a potential therapeutic role against progression
      of anti-inflammation and lung damage.

PMID- 23544310
TI  - [Autoinflammatory diseases: a glimpse at the innate immunity and its pathology].

PMID- 23544309
TI  - [Toll-like receptors in development and function of the hematopoietic system].
AB  - Virus, bacteria, fungi and parasites are pathogens to which individuals are
      constantly exposed. Pathogen recognition by cells of the immune system is carried
      out by a growing list of pattern-recognition receptors (PRRs) which are
      evolutionally conserved and absent in mammals, named pathogen-associated
      molecular patterns (PAMPs). PRRs can be found in extracellular matrix, within
      cytoplasm and on cellular membranes. Among the membrane PRRs, Toll-like receptors
      (TLRs) induce the production of pro-inflammatory cytokines and the expression of
      co-stimulatory molecules upon stimulation on mature cells, resulting in the
      triggering of immune danger signals. Recent reports showing the regulation of
      hematopoiesis by TLRs, suggest that they are involved in the most primitive
      stages of hematopoietic development and contribute to emergent replenishment of
      innate immune cells. These data entail TLRs to hematopoiesis and also
      revolutionize our understanding of the mechanisms governing infection responses.
      In this review, we focus on the most relevant findings from the TLR discovery to
      the use of TLR agonists and antagonists in novel therapies for infectious,
      autoimmune and neoplastic diseases. Of special interest is the research progress
      in the TLR functional expression by primitive hematopoietic stem and progenitor
      cells.

PMID- 23544311
TI  - [Adeno-associated viral vectors: methods for production and purification for gene
      therapy applications].
AB  - Viral vectors based on adeno-associated virus (AAV) are widely used in gene
      therapy protocols, because they have characteristics that make them valuable for
      the treatment of genetic and chronic degenerative diseases. AAV2 serotype had
      been the best characterized to date. However, the AAV vectors developed from
      other serotypes is of special interest, since they have organ-specific tropism
      which increases their potential for transgene delivery to target cells for
      performing their therapeutic effects. This article summarizes AAV generalities,
      methods for their production and purification. It also discusses the use of these
      vectors in vitro, in vivo and their application in gene therapy clinical trials.

PMID- 23544312
TI  - [Frequency of mucopolysaccharidoses diseases at the Hospital Infantil de Mexico
      Federico Gomez].

PMID- 23544313
TI  - 'Europe divided will become more and more united'.

PMID- 23544314
TI  - Prisoners right to healthcare, a European perspective.
AB  - The right to healthcare applies regardless of a person's legal status. Prisoners
      have a right to a healthcare equivalent to the one in the community at large:
      access to medical care and preventive measures of good quality and costs covered.
      States have a positive duty to provide for appropriate healthcare in prison,
      including harm reduction policies (for instance health screening, vaccination and
      needle exchange). Denial of access to appropriate health facilities to prisoners
      and other detainees is likely to result in bodily harm, unnecessary morbidity and
      avoidable death. Essential elements of the social right to care for the health of
      prisoners are protected through the positive obligations individual human rights
      impose on States (e.g., the right to life, the prohibition of torture, degrading
      treatment and punishment, the right to liberty and the right to private life).
      Health related human rights standards for prison healthcare have been formulated
      over worldwide and in Europe. The Council of Europe's Committee of Prevention of
      Torture monitors the situation of prisoners in Member States. Still, healthcare
      for prisoners falls short of what is required. Prison healthcare is an essential
      part of public health. A major involvement of the Minister of Health is
      indispensable.

PMID- 23544315
TI  - A new approach to sex-based classifications in the context of procreative rights:
      S.H. & Others V. Austria in context.
AB  - A critical discussion of the recent First Section and Grand Chamber judgments of
      the European Court of Human Rights in the case of S.H. and Others v. Austria,
      which upheld an Austrian ban on in-vitro fertilisation (IVF) using donor gametes
      (ova and sperm). The author argues that the regulatory regime adopted by Austria
      is overbroad insofar as the regime it adopts fails to accurately reflect the
      legitimate interests of the state. This is not a conventional "controversial
      morals" case where, in the absence of a clear moral and/or policy consensus among
      the Council of Europe member states, states are properly accorded a wide margin
      of appreciation. The regime adopted by Austria embodies a clear sex bias (with
      their respective gametes standing as near perfect proxies for the sex of the
      applicants) with exceptions being made to address male infertility while leaving
      women without medical remedy. As such, the margin of appreciation should be
      significantly restricted and the classifications embodied by the regime subject
      to the highest possible scrutiny.

PMID- 23544316
TI  - Living organ donation and minors: a major dilemma.
AB  - In this article, the case of living organ donation by minors is discussed. A
      distinction can be made between minors who are in fact already competent and
      those who are not. Minors who are in fact competent, should be able to decide on
      organ donation under the same conditions as competent adults. Incompetent minors
      could be allowed to act as living organ donors under exceptional circumstances on
      the basis of a best interest test. Decisions on living organ donation by
      incompetent minors should be embedded into a procedural framework in which
      parental consent, the approval of an independent body of health professionals,
      and the minor's wishes play a substantial role.

PMID- 23544317
TI  - Risk assessment vs. right to privacy: the access to health information on the
      insurance candidate through questionnaires and the right to privacy.
AB  - The need of private insurers for information on the candidate's health risks is
      recognized by the law, which places pre-contractual duties of disclosure upon the
      candidates. When the risks are influenced by health factors, e.g. in the case of
      life- and health insurances, it implies the provision of health information by
      the candidates, who thus voluntarily limit their right to privacy. This consent,
      however, often happens in a context of factual coercion to contract. Next to
      this, from a legal standpoint, the collection of personal information must
      respond to the principle of proportionality. Against this background, this
      article assesses the compatibility of questionnaire techniques that rely on open
      ended health related questions with the right to privacy, as protected by
      Portuguese and international law. It then analyses the extent of pre-contractual
      duties of disclosure as defined by the Portuguese Insurance Act, which requires
      the candidate to volunteer all the relevant information independently of being
      asked for it. In doing so, the article also refers to some other European
      countries. It concludes that the relevant Portuguese legislation is incompatible
      both with Portuguese constitutional law and with international law.

PMID- 23544318
TI  - ECHR 2013/1 Case of Koch v. Germany, 19 July 2012, no. 497/09 (Former Fifth
      Section).

PMID- 23544319
TI  - ECHR 2013/2 Case of Munjaz v. The United Kingdom, 17 July 2012, no. 2913/06
      (Fourth Section).

PMID- 23544320
TI  - ECHR 2013/3 Case of Liuiza v. Lithuania, 31 July 2012, no. 13472/06 (Second
      Section).

PMID- 23544321
TI  - ECHR 2013/4 Case of Van der Velden v. The Netherlands, 31 July 2012, no. 21203/10
      (Third Section).

PMID- 23544322
TI  - ECJ 2012/11, Brain Products GmbH v. BioSemi VOF, et al, 22 November 2012 (C
      219/11).

PMID- 23544323
TI  - Danish medical doctor reprimanded for treatment of a four week-old child
      following reporting from the National Board of Health.

PMID- 23544324
TI  - [Bright and dark sides of the operating room efficiency--general ward is
      dangerous].

PMID- 23544325
TI  - [Translational research in anesthesiology: preface and comments].
AB  - According to Wikipedia, translational research is scientific research that
      facilitates the translation of findings from basic science to practical
      applications that enhance human health and well-being. In this special issue, the
      topic of translational research in anesthesiology was featured. Six subtopics
      including 1) adaptation of induced pluripotent stem (iPS) cells to central nerve
      injury, 2) signaling of granulocyte macrophage colony stimulating factor and its
      clinical application: host-defense and organ protection, 3) molecular mechanisms
      of chronic pain and its therapeutic strategy, 4) endoplasmic reticulum stress and
      opioid tolerance, 5) relationships of damage-associated molecular patterns and
      organ injury, and 6) translational research in omics science to clinical
      anesthesia, are presented and discussed in detail. Anesthesiologists always keep
      in mind that the goal of translational research is to improve our health through
      research and that there would be no bright future in anesthesiology without the
      fruits of translational research.

PMID- 23544326
TI  - [Application of induced pluripotent stem (iPS) cells for nerve injury in the
      central nervous system].
AB  - Induced pluripotent stem cells (iPSCs), with both pluripotency and replication
      competence similar to embryonic stem cells (ESCs), have been developed from mouse
      fibroblasts in 2006 by Yamanaka et al. iPSCs are unique in employing somatic
      cells for their production, and can avoid ethical issues existing in ESCs. It is
      clear that progress in technology to produce iPSCs is one of the most crucial
      achievements of medicine in this century. Technology with the new pluripotent
      cells will offer many advantages in the field of regeneration medicine supplying
      new tissues to the injured organ and/or development of methodology to uncover
      many genetic diseases. On the other hand, we have to await adequate progress in
      issues regarding iPSCs, including enhanced efficiency to obtain iPSCs, the
      technology to produce organs from the cells, avoidance of tumorigenesis and
      decrease in immunity in response to iPSCs.

PMID- 23544327
TI  - [Signaling of granulocyte macrophage colony stimulating factor and its clinical
      application: host-defense and organ protection].
AB  - Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine with
      multipotent properties. It has not only an activity to generate both granulocyte
      and macrophage lineages in the bone marrow, but also is capable of inducing
      terminal maturation of alveolar macrophages that is central for pulmonary host
      defense and pulmonary surfactant homeostasis. GM-CSF can stimulate mature myeloid
      cells (i.e. neutrophils and monocytes) with a known mechanism called "priming" to
      efficiently eliminate invading pathogens. Several clinical trials to evaluate
      therapeutic efficacy of GM-CSF in patients with diseases related to functional
      impairment of mature myeloid cells were reported. Inhalation of GM-CSF improved
      clinical severity of pulmonary alveolar proteionosis. Administration of GM-CSF
      for patients with immune compromised situation such as sepsis showed marginal
      benefits so far. Several animal experiments indicated neuroprotective effect of
      GM-CSE In the clinical setting, establishing reliable biomarkers to distinguish
      patients who will have benefit by administering GM-CSF may maximize its clinical
      efficacy.

PMID- 23544328
TI  - [Molecular mechanisms of chronic pain and its therapeutic strategy].
AB  - The contribution of numerous molecules for developing and maintaining the chronic
      pain state in patients has been gradually shown after the decade of pain control
      and research. However, many patients still have chronic pain which is difficult
      to treat even after the appearance of new analgesics. Therefore, a number of
      studies are still ongoing to find promising novel analgesics. We review several
      molecules being examined in ongoing studies including ionotropic and G-protein
      coupled receptors, which are mainly distributed in primary sensory afferents
      and/or spinal cord dorsal horn neurons.

PMID- 23544329
TI  - [Endoplasmic reticulum stress and opioid tolerance withdrawal].
AB  - Morphine is a potent analgesic, but its molecular mechanism for tolerance
      formation is not fully understood. Binding immunoglobulin protein (BiP) is an
      endoplasmic reticulum (ER) chaperone that is central to ER functions. We examined
      knock-in mice expressing a mutant BiP with the retrieval sequence deleted in
      order to elucidate physiological BiP functions. We tested thermal antinociceptive
      effects of morphine on heterozygous mutant BiP mice by a hot plate test. Repeated
      morphine administration caused the development of morphine tolerance in the wild
      type mice. The activation of glycogen synthase kinase 3beta (GSK3beta) was
      associated with morphine tolerance, since an inhibitor of GSK3beta prevented it.
      On the other hand, the mutant BiP mice showed less morphine tolerance, and the
      activation of GSK3beta was suppressed in their brain. These results suggest that
      BiP may play an important role in the development of morphine tolerance.
      Furthermore, we found that a chemical chaperone that improves ER protein folding
      capacity also attenuated the development of morphine tolerance in wild-type mice,
      suggesting a possible clinical application of chemical chaperones in preventing
      morphine tolerance.

PMID- 23544330
TI  - [Relationships between damage-associated molecular patterns and organ injury].
AB  - Recently studies have demonstrated that cell components called damage-associated
      molecular patterns (DAMPs) are secreted from cells in response to inflammation
      and organ injury. While DAMPs are maintained within the cell under normal
      conditions, they are secreted in response to systemic or chronic inflammation.
      DAMPs are recognized by pattern recognition receptors (PRRs) such as Toll-like
      receptor (TLR) and receptor for advanced glycation end products (RAGE). DAMPs
      also induce the phosphorylation of various intracellular proteins and activate NF
      kappaB signaling. This induces an inflammatory response via cytokine production
      and activation of macrophages and dendritic cells. In essence, DAMPs alert the
      immune system to danger. Some DAMPs are considered therapeutic targets for acute
      systemic inflammation (e.g., sepsis). Indeed, anti-HMGB1 and anti-histone
      antibodies attenuated the inflammatory response and organ injury in a systemic
      inflammation model. Anti-RAGE antibodies were also shown to have beneficial
      effects in an animal inflammation model. These findings suggest that DAMPs may
      serve as novel therapeutic targets against severe systemic inflammation as well.
      We anticipate that in the near future, anti-DAMP therapy may become more
      widespread in the clinical setting.

PMID- 23544331
TI  - [Introduction of translational research in omics science to clinical anesthesia].
AB  - Much progress has been made in omics research following completion of the Human
      Genome Project. This comprehensive analysis produced a new discipline (i.e.,
      bioinformatics), and its findings contributed to the clinical practice of
      anesthesiology. Genomes of patients show genetic variations and may predict the
      sensitivity to anesthetics and analgesics, incidence of adverse effects, and
      intensity of postsurgical pain. Changes in the transcriptomes of patients may
      also reflect anesthesia-related expression profiles of various types of neurons
      in the brain, and information on such changes may contribute to molecular
      targeted therapy in anesthetized patients. In addition, novel epigenome research
      may explain why environments change the phenotypes of clinical anesthesia. We
      currently hypothesize that female gender is associated with DNA methylation in
      pain-related and vomiting-related gene promoter regions at the genome-wide level
      and that epigenetic mechanisms are involved in gender differences in anesthesia
      practice.

PMID- 23544332
TI  - [The effect of rocuronium and sugammadex in hepatic tumor patients without
      preoperative hepatic impairment].
AB  - BACKGROUND: The effect of rocuronium and sugammadex in patients undergoing
      hepatectomy due to hepatic tumor without preoperative hepatic impairment were
      investigated. METHODS: We studied 15 patients undergoing hepatectomy and 20
      patients undergoing non-hepatic surgery No patients had preoperative hepatic
      impairment. Anesthesia was induced and maintained with propofol and remifentanil.
      Train-of-four (TOF) responses of the adductor pollicis to the supramaximal ulnar
      nerve stimulation were monitored by acceleromyography. A single dose of
      rocuronium 0.9 mg x kg(-1) was administered, and after spontaneous recovery of T1
      to 25%, rocuronium was infused continuously to keep the posttetanic count 1-2.
      After surgery, sugammadex 4 mg x kg(-1) was administered. RESULTS: In hepatectomy
      patients, duration from the administration of rocuronium to recovery of T1 to 25%
      was longer (88 +/- 20 vs 68 +/- 16 min, P < 0.01), and the total dose of
      rocuronium used during surgery was less (8.8 +/- 1.7 vs 11.4 +/- 2.7 microg x kg(
      1) x min(-1), P < 0.01). However, there were no differences in the duration from
      administration of sugammadex to recovery of TOF ratio to 0.9 between two groups
      (138 +/- 55 vs 164 +/- 79 sec, P = 0.29). CONCLUSIONS: Rocuronium-induced
      neuromuscular block was prolonged in hepatectomy patients even without
      preoperative hepatic impairment but the reversal with sugammadex was effective.

PMID- 23544333
TI  - [The preventive effect of flurbiprofen on preventing mesenteric traction
      syndrome].
AB  - BACKGROUND: Mesenteric traction syndrome (MTS) is associated with facial
      flushing, hypotension and tachycardia. The ways to treat MTS are fluid
      replacement, administration of vasopressors and nonsteroidal anti-inflammatory
      drugs (NSAIDs) such as flurbiprofen. In order to stabilize the hemodynamics
      during operation, preventing MTS is more reasonable. Thus, we investigated the
      preventive effect of flurbiprofen on MTS, the only injectable formulation which
      can be used in Japan. METHODS: In a prospective randomized study, 24 patients
      undergoing elective colorectal surgery were assigned to two groups. In one group
      (n = 11 group F), flurbiprofen (1 mg x kg(-1), 50 mg max) was administered before
      surgery. In the second group (n = 13; group C), flurbiprofen was not
      administered. After laparotomy, presence of facial flushing and blood pressure
      reduction were compared. MTS is defined as facial flushing with concomitant blood
      pressure reduction. RESULTS: MTS occurred in no patients in group F, but in 11
      patients in group C (84.6%, P < 0.05). In cases of the patients in which MTS
      appeared, facial flushing was observed at 5.9 +/- 5.2 min after starting
      mesenteric manipulation, and the mean reduction in blood pressure was 40.3% at
      9.9 +/- 4.4 min after starting mesenteric manipulation. CONCLUSIONS: Our results
      indicate that pretreatment with flurbiprofen might prevent MTS.

PMID- 23544334
TI  - [A case of intracranial subdural hematoma after thoracic epidural anesthesia].
AB  - Intracranial subdural hematoma (SDH) occurred in a 58-year-old female after
      laparoscopy-assisted distal gastrectomy under general and thoracic epidural
      anesthesia. On postoperative day 2, she complained of headache in sitting
      position, but there were no remarkable neurological defect and nausea. On
      postoperative day 5, her headache subsided and she could walk by herself. But on
      postoperative day 10, she felt heavy-headed again, and complained sensory
      abnormality of her right leg. Magnetic resonance imaging of the head showed small
      acute subdural hematoma in bilateral parietal regions with no mass effect. She
      was managed conservatively with bed rest and intravenous fluids. Her condition
      improved and was discharged on postoperative day 17 without subsequent
      complications. SDH after epidural anesthesia is rare, but diagnosis in early
      stage has a decisive influence on its prognosis. It is crucial to exclude the
      possibility of SDH and observe closely if the patient complains of severe
      headache or another unexplained symptom only with postdural puncture headache.

PMID- 23544335
TI  - [A case report of coronary artery fistula in which perioperative transthoracic
      and transesophageal echocardiography was useful for surgical decision].
AB  - Coronary artery fistula is rare in congenital heart diseases but is the major
      disease among "coronary" congenital diseases. In a coronary artery fistula, the
      coronary artery tip connects directly or via an unusual blood vessel to unusual
      parts, such as the inside of the heart chamber, pulmonary artery or superior vena
      cava. Left ventricular volume overload and coronary steal phenomenon are serious
      symptoms. The gold standard of diagnosis has been coronary angiography, but
      echocardiography using Doppler methods is now useful for its diagnosis. This is a
      case report of coronary artery fistula for which transthoracic echocardiography
      (TTE) during anesthetic induction and intraoperative transesophageal
      echocardiography (TEE) by anesthesiologists provided accurate diagnosis of the
      shunt position. A 62-year-old female was scheduled to undergo surgery for a
      coronary artery fistula and aneurysm. Two separate shunts from the coronary
      artery into the pulmonary artery had been suspected by preoperative TTE. Shunt
      orientation was reexamined by perioperative TTE and TEE. We confirmed that only
      one shunt was located at the supra pulmonary valve area, and we consulted the
      diagnosis to surgeons. As a result, one shunt was found in the surgical view at
      the same position. Perioperative TTE and TEE are useful for surgical decision.

PMID- 23544336
TI  - [Bilateral transversus abdominis plane block using catheterization for a patient
      with severe cardiac dysfunction and chronic kidney failure: a case report].
AB  - The transversus abdominis plane (TAP) block is a newly described technique
      introducing a local anesthetic agent between the internal oblique and the
      transversus abdominis muscles of the abdominal wall, which is safer and more
      reliable analgesia in recent years by ultrasound technique. We report the
      perioperative management of transversus abdominis plane block with
      catheterization for a patient with severe cardiac dysfunction and chronic kidney
      failure, who underwent bilateral inguinal hernioplasty. A bilateral TAP block was
      first performed with 0.5% ropivacaine 20 ml under ultrasonographic visualization
      on right side, and after sixty-minutes the other side injection was performed
      through the indwelling catheter. During the operation, the patient received a
      target-controlled infusion of 0.4-0.6 microg x ml(-1) propofol. The perioperative
      courses were uneventful and there was no adverse effect including central nervous
      system (CNS) symptoms.

PMID- 23544337
TI  - [Anesthetic management for laparoscopic Nissen fundoplication in a 18 trisomy
      patient with congestive heart disease].
AB  - A 21-month-old patient diagnosed as 18 trisomy, having large ventricular septal
      defect with pulmonary valve stenosis, and gastroesophageal reflux disease, was
      admitted for laparoscopic Nissen fundoplication and gastrostomy. Anesthesia was
      induced with midazolam, fentanyl, and rocuronium, and maintained with sevoflurane
      and remifentanil. After induction of anesthesia, oxygenation became worse,
      possibly due to diminished pulmonary blood flow, which was partially resolved
      with vasopressor administration and fluid infusion. After the abdomen was
      insufflated, oxygenation improved significantly. We supposed that an increase in
      systemic vascular resistance due to O2 insufflation augmented pulmonary blood
      flow and improved the oxygenation. She was extubated the next day and recovered
      uneventfully. However, we should bear in mind that 18 trisomy patients are
      frequently complicated by congestive heart disease, and require caution for
      hemodynamic changes during anesthesia.

PMID- 23544338
TI  - [A case of a giant ovarian cyst anesthetized with the use of an inferior vena
      cava filter].
AB  - An intraperitoneal giant tumor can form deep venous thrombosis (DVT), leading to
      pulmonary embolism (PE) when it is removed. We report a case of a giant ovarian
      cystic tumor with possible DVT. A 52-year-old woman (149 cm in height, 85 kg in
      weight, and 150 cm in ventral girth) underwent the laparoscopic resection of the
      cyst. Preoperative angiography showed the obstruction of the inferior vena cava
      (IVC) just below the level of the right renal vein due to the compression by the
      tumor, and computed tomography suggested the existence of distal DVT. Anesthesia
      was induced with propofol and fentanyl, and the trachea was intubated using
      rocuronium. A permanent type IVC filter was placed near the obstruction site to
      prevent PE. Transesophageal echocardiography (TEE) was employed to detect the
      thrombotic echogram at the right atrium. Anesthesia was maintained with
      inhalation of sevoflurane and intravenous infusion of remifentanil. The content
      of the cyst (40.5 l) was suctioned slowly in about 50 min to avoid reexpansion
      pulmonary edema and circulatory collapse. Neither thrombotic echogram nor the
      acute decrease in end-tidal carbon dioxide pressure was observed throughout the
      anesthesia. Operation was performed uneventfully, and she recovered from
      anesthesia. We consider that IVC filters and TEE are useful to manage surgical
      patients with a huge ovarian cyst.

PMID- 23544339
TI  - [Anesthetic management of an emergency open-heart surgery for entrapment of a
      circular mapping catheter by chordae tendineae with mitral valve damage
      undergoing atrial fibrillation ablation].
AB  - The entrapment of a circular mapping catheter by chordae tendineae during
      catheter ablation is a very rare but serious complication requiring, in some
      cases, surgical treatment. We report a case that required open heart surgery for
      catheter removal and mitral valve repair. A 79-year-old man underwent catheter
      ablation for paroxysmal atrial fibrillation in other hospital. During the
      operation, he moved accidentally, despite circular mapping catheter was in the
      left atrium. The circular mapping catheter was uncontrolable due to resistance
      interfering with catheter removal, and the patient was brought to our hospital
      for open heart surgery to remove catheter. General anesthesia was induced and
      maintained with midazolam, fentanyl. Transesophageal echocardiography was
      performed to monitor catheter position and mitral valve condition.
      Transesophageal echocardiography revealed that circular catheter tip was located
      adjacent to the posterior mitral leaflet and the presence of moderate mitral
      valve regurgitation. Circular catheter tip was entraped by chordae tendineae and
      caused posterior mitral leaflet damage. Intracardiac foreign body removal and
      posterior mitral leaflet repair were completed uneventfully under cardiopulmonary
      bypass. The postoperative course was uneventful. It is expected that catheter
      ablation for atrial fibrillation will increase in number. This rare complication
      of catheter ablation may become a threat to cardiologist, cardiac surgeon and
      anesthesiologist.

PMID- 23544340
TI  - [Cervical spine movement during bag-mask ventilation].
AB  - BACKGROUND: Every airway maneuver will cause some degree of neck movement.
      Ventilation via face-mask technique requires lifting the mandible (jaw thrust) to
      the facemask. A significant degree of cervical spine motion induced by bag-mask
      ventilation has been reported on human cadavers with destabilized cervical
      vertebrae. However, to our knowledge, no quantitative data have reported
      evaluating the effects of bag-mask ventilation on cervical spine motion in living
      humans. We measured the cervical spine movement during bag-mask ventilation.
      METHODS: Twenty patients requiring general anesthesia were studied. Each patient
      underwent bag-mask ventilation. Movements of cervical spine were measured by
      radiography in the same patient both at neutral head position and during bag-mask
      ventilation. RESULTS: The anterior movements of the vertebral bodies from
      baseline were 11.3 +/- 5.8 mm, 11.1 +/- 4.9 mm, 11.0 +/- 4.7 mm and 10.6 +/- 4.4
      mm at the atlas, C2, C3, and C4 vertebrae, respectively, during bag-mask
      ventilation. The changes in angle during bag-mask ventilation were 7.4 +/- 4.5
      degrees, 4.9 +/- 4.2 degrees, 1.7 +/- 3.2 degrees, and -0.1 +/- 2.3 degrees, at
      occiput/C1, C1/C2, C2/C3, and C3/C4 motion segments, respectively. The total
      change in angle between the occiput and C4 was 13.8 +/- 6.4 degrees (95% CI 10.9
      degrees-16.8 degrees). CONCLUSIONS: The lifting the mandible causes both
      extension and anterior disposition in the cervical vertebrae.

PMID- 23544341
TI  - [A case of prolonged hypercapnea after interscalene brachial plexus block].
AB  - An 83-year-old woman was scheduled for surgery of the left upper and lower
      extremity fracture. She had past history of lung partial resection for lung
      cancer and rheumatoid arthritis, and recent history of pneumonia. She also had
      fluid retention in the thoracic cavity. Open resection of the femoral neck
      fracture was first performed uneventfully under spinal anesthesia with
      bupivacaine 0.5% 2 ml. Then, interscalene blaxioplexus block was performed with
      0.75% ropivacaine 15 ml and 1% lidocaine 10 ml for tension band wiring of the
      fractured olecranon. Midazolam 1 mg and propofol 1.5 mg x kg(-1) x hr(-1) were
      administered for sedation. Thirty minutes after the block, oxgen saturation
      decreased to 92% under O2 3 l x min(-1) by a mask. She was intubated and arterial
      carbon dioxide tension was above 150 mmHg. A few hours later, she became
      conscious and mask CPAP was used after extubation for one day. Pa(CO2) was 90-100
      mmHg for 3 days and decreased to 56.9 mmHg on the 6th day, but her consciousness
      had been clear. Phrenic nerve palsy and sedation in the patient with decreased
      lung function might have induced prolonged hypercapnea.

PMID- 23544342
TI  - [Successful internal jugular venipuncture in an infant with a high risk of
      puncturing the vertebral artery].
AB  - A five-month-old baby girl, 61.8 cm in height and weighing 4.9 kg, underwent
      ventricular septal defect repair under general anesthesia. Authors checked for
      small vessels around the IJV using an ultrasound echo apparatus with a 5/10-MHz
      probe (TiTAN, SonoSite Co., Tokyo, Japan) at a point 28 mm from the clavicle over
      the IJV. We observed a 3.8-mm-wide and 8.7-mm-deep vertebral artery 1.3 mm behind
      the 5.5-mm-wide IJV with color Doppler flow imaging for CVC. It seemed difficult
      to avoid puncturing the vertebral artery. We checked for small arteries again at
      a point 40 mm from the clavicle. We also confirmed the 3.2-mm-wide and 13.4-mm
      deep vertebral artery 5.3 mm behind the IJV. It thus seemed possible to avoid
      puncturing the vertebral artery at this point. The operator punctured the IJV
      carefully using real-time ultrasound guidance with a 24 G plastic puncture needle
      (Jelco Plus, Smith Medical, Tokyo, Japan), and avoided puncturing the vertebral
      artery. The CVC was successful, and no after-effect was observed following the
      operation. Before inserting the puncture needle each time, one should check for
      small arteries behind the IJV with color Doppler flow imaging.

PMID- 23544343
TI  - [Anesthesia for removal of a screw compressing the aorta after posterior spinal
      surgery].
AB  - Iatrogenic vascular injury in posterior spinal surgery is a rare but potentially
      serious complication. We describe anesthetic management of a pedicle screw
      removal after posterior spinal surgery. A 60-year-old man underwent posterior
      spinal fusion due to ossification of posterior longitudinal ligament, but
      postoperative computed tomography scans of the chest demonstrated a compression
      of the posterior wall of the thoracic aorta by the pedicle screw at T10.
      Therefore, he was scheduled for screw removal. Surgery was performed in the right
      lateral decubitus position for emergency surgery. An occlusion balloon catheter,
      percutaneous cardiopulmonary support and a rapid infusion system were prepared in
      anticipation of massive hemorrhage. The operation was completed successfully
      without any adverse events. In conclusion, although major vascular injury during
      posterior spinal fusion is rare, we should be careful of massive hemorrhage.

PMID- 23544344
TI  - [A case of malignant hyperthermia with evident symptoms in the postoperative
      period].
AB  - A 36-year-old man (185 cm tall, weighing 85 kg) was scheduled for fixation of a
      right carpal bone fracture. He had no operative history, and his preoperative
      laboratory data were normal. A laryngeal mask was inserted after intravenous
      propofol and fentanyl administration without a muscle relaxant. Anesthesia was
      maintained by sevoflurane in a mixture of air and oxygen. A tourniquet was placed
      on the right upper arm. One hour after the operation, his heart rate increased to
      90-100 beats x min(-1) from 70-80 beats x min(-1) at the start of the operation,
      and tachycardic continued, even after release of the tourniquet. Although end
      tidal CO2 was 50-60 mmHg, his body temperature remained 37.6 degrees C, and
      neither muscle stiffness nor brown urine was observed. The duration of the
      operation and the duration of anesthesia were 2 hours 40 min and 4 hours,
      respectively. The patient went back to the ward without myalgia after removal of
      the laryngeal mask. On the postoperative day one, the patient had brown urine. On
      the postoperative day 2, he experienced myalgia of the upper and lower
      extremities and masseter muscle. On the postoperative day 3, myoglobinuria was
      detected. As in this case, although evident symptoms of malignant hyperthermia
      are not always observed during operations, some cases show obvious symptoms
      during the postoperative period. Thus, it is important to be aware of the
      symptoms of malignant hyperthermia postoperatively for early diagnosis and
      treatment.

PMID- 23544345
TI  - [Anesthetic management of a patient with carnitine palmitoyltransferase
      deficiency with a history of rhabdomyolysis].
AB  - Carnitine palmitoyltransferase (CPT) makes the fatty acids available through beta
      oxidation. Deficiency of CPT causes difficulties of muscle cells to metabolize
      fatty acid. In affected patients, exercise, fast for a prolonged period, and
      stress, lead to exhaustion of the store of glucose in the body, and
      rhabdomyolysis may occur, since muscle can not utilize fatty acid as an
      alternative energy source. Therefore, anesthetic management of CPT deficiency
      needs infusion of glucose continuously, avoiding the use of the drugs that cause
      rhabdomyolysis and suppressing the surgical stress. A 67-year-old man, who had
      previous history of rhabdmyolysis during the postoperative period, and diagnosed
      CPT deficiency was scheduled for total gastrectomy. General anesthesia was
      induced with remifentanil, thiamylal and rocuronium after epidural catheter
      insertion. During surgery, general anesthesia was maintained with remifentanil,
      sevoflurane, and blood glucose was monitored frequently, with continuous glucose
      infusion. No complications occurred during anesthesia and perioperative course
      was uneventful.

PMID- 23544346
TI  - [Perioperative management of a child with central diabetes insipidus who
      underwent two surgeries before and after desmopressin administration].
AB  - A 14-year-old girl weighing 32 kg was diagnosed with suprasellar tumor causing
      hydrocephalus, hypothyroidism, adrenal dysfunction and central diabetes
      insipidus. She was treated with levothyroxine and hydrocortisone and urged to
      take fluid to replace urine. She was scheduled to undergo ventricular drainage to
      relieve hydrocephalus prior to tumor resection. For the first surgery,
      desmopressin was not started and urine output reached 4,000 to 6,000 ml x day(
      1), urine osmolality 64 mOsm x l(-1) and urine specific gravity 1.002. Anesthesia
      was induced with sevoflurane and maintained with propofol and remifentanil.
      Maintenance fluid was with acetated Ringer's solution and urine loss was replaced
      with 5% dextrose. Bradycardia and hypotension occurred after intubation, which
      was treated with volume load. Infusion volume was 750 ml and urine output was
      1100 ml during 133 min of anesthesia. Postoperative day 1 nasal desmopressin was
      started. Ten days later, partial tumor resection was performed. Anesthesia was
      induced with propofol and fentanyl and maintained with sevoflurane and
      remifentanil. Infusion volume was 610 ml, urine output 380 ml, and blood loss 151
      ml during 344 min of anesthesia. Hemodynamic parameters were stable throughout
      the procedure. Pathology of the tumor was revealed to be germinoma. Bradycardia
      and hypotension experienced during the first surgery was suspected to be caused
      by preoperative hypovolemia brought by polyuria. Desmopressin was proved to be
      effective to treat excessive urine output and to maintain good perioperative
      water balance.

PMID- 23544347
TI  - [A case of respiratory distress due to massive pleural effusion after surgery for
      ovarian tumor].
AB  - A 59-year-old woman with ovarian tumor was scheduled for radical hysterectomy
      under general anesthesia. Preoperative examination showed massive ascites and
      slight pleural effusion. Since respiratory status had improved by oxgen therapy,
      she underwent a surgery as scheduled, although she complained of slight dyspnea
      and low Sp(O2). Induction of anesthesia was uneventful. However, oxygenation
      deteriorated and airway pressure increased after suction of ascites during the
      operation. We treated it with increased FI(O2). After surgery, we found bilateral
      massive pleural effusion on the chest X-ray and drained it. Oxygenation improved,
      and the endotracheal tube was removed. Patients with ovarian tumor with pleural
      effusion and ascites may have desaturation due to increased pleural effusion
      during the operation, or pleural effusion might increase preoperatively.
      Therefore, we need to be cautious about anesthetic management of them and examine
      chest X-ray and arterial blood gas frequently.

PMID- 23544348
TI  - [Wasn't the postoperative cardiac arrest caused by hyperkalemia?].

PMID- 23544350
TI  - [Preformed pediatric endotracheal tubes].
AB  - BACKGROUND: The goal of this investigation was to evaluate the details of
      preformed pediatric endotracheal tubes (PPETTs, I. D. 3.0-6.0 mm). METHODS:
      Dimensions of all PPETTs were measured as follows: the distance from tube tip to
      the distal border of depth markings, length and the number of depth markings,
      outer diameter and length of the tubes, the distance from tube tip to the bent
      section, the number of the Murphy eyes and calculated cross sectional area of the
      Murphy eyes, the distance from tube tip to the distal/proximal border of the
      cuff, cuff diameter and cuff volume at 20 cmH2O cuff pressure. RESULTS: A total
      of 80 PPETTs, including 18 brands from 5 manufacturers, were investigated, of
      which 30% of PPETTs are cuffed tubes. There are significant variability in the
      distance from tube tip to the bent section, the number and position of depth
      markings, the number of the Murphy eyes and position and diameter of cuff at 20
      cmH2O cuff pressure for a given I. D. CONCLUSIONS: There are no uniformity in the
      details of PPETTs. The details of PPETTs including those with high volume low
      pressure cuff should be updated.

PMID- 23544351
TI  - Generation 9 polyamidoamine dendrimer encapsulated platinum nanoparticle mimics
      catalase size, shape, and catalytic activity.
AB  - Poly(amidoamine) (PAMAM) encapsulated platinum nanoparticles were synthesized and
      used as catalase mimics. Acetylated generation 9 (Ac-G9) PAMAM dendrimer with a
      molecular size around 10 nm was used as a template to synthesize platinum
      nanoparticles. The feeding molar ratio of Pt(4+) and Ac-G9 is 2048, and the
      synthesized platinum nanoparticle (Ac-G9/Pt NP) has an average size of 3.3 nm. Ac
      G9/Pt NP has a similar molecular size and globular shape with catalase (~11 nm).
      The catalytic activity of Ac-G9/Pt NP on the decomposition of H2O2 is approaching
      that of catalase at 37  degrees C. Ac-G9/Pt NP shows differential response to the
      changes of pH and temperature compared with catalase, which can be explained by
      different catalytic mechanisms of Ac-G9/Pt NP and catalase. Ac-G9/Pt NP also
      shows horseradish peroxidase activity and is able to scavenge free radicals such
      as di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH). Furthermore, Ac-G9/Pt NP
      shows excellent biocompatibility on different cell lines and can down-regulate
      H2O2-induced intracellular reactive oxygen species (ROS) in these cells. These
      results suggest that dendrimers are promising mimics of proteins with different
      sizes and Ac-G9/Pt NP can be used as an alternative candidate of catalase to
      decrease oxidation stress in cells.

PMID- 23544352
TI  - Simultaneous determination of nine trace organophosphorous pesticide residues in
      fruit samples using molecularly imprinted matrix solid-phase dispersion followed
      by gas chromatography.
AB  - How to determine trace multipesticide residues in fruits is an important problem.
      This paper reports a molecularly imprinted polymer (MIP) that was prepared using
      4-(dimethoxyphosphorothioylamino)butanoic acid as the template, acrylamide as the
      functional monomer, and ethylene glycol dimethacrylate (EGDMA) as the cross
      linker. The novel imprinted polymer was characterized by static and kinetic
      adsorption experiments, and it exhibited good recognition ability and fast
      adsorption-desorption dynamicd toward trichlorfon, malathion, acephate,
      methamidophos, omethoate, dimethoate, phosphamidon, monocrotophos, and methyl
      parathion. Using this imprinted polymer as sorbent, matrix solid-phase dispersion
      coupled to gas chromatography for simultaneous determination of nine trace
      organophosphorus pesticide residues was first presented. Under the optimized
      conditions, the LOD (S/N = 3) of this method for the nine organophosphorus was
      0.3-1.6 MUg kg(-1); the RSD for three replicate extractions ranged from 1.2 to
      4.8%. The apple and pear samples spiked with nine organophosphate pesticides at
      levels of 20 and 100 MUg kg(-1) were determined according to this method with
      good recoveries ranging from 81 to 105%. Moreover, this developed method was
      successfully applied to the quantitative detection of the nine organophosphorus
      pesticide residues in orange samples. 

PMID- 23544353
TI  - Single-cell elemental analysis via high irradiance femtosecond laser ionization
      time-of-flight mass spectrometry.
AB  - In modern bioanalytics, elemental analysis of single cells is important yet
      challenging due to the complicated biological matrices and elemental contents. We
      have developed the high irradiance femtosecond laser ionization orthogonal time
      of-flight mass spectrometry (fs-LI-O-TOFMS) to determine the elemental
      composition of individual cells. The sample preparation procedure is simple and
      fast through heating and drying the cells. Under typical operating conditions,
      elements above femtogram levels in a single cell can be clearly observed in the
      spectrum with reasonable isotope ratios. Some of the nonmetallic elements that
      are difficult to measure by ICPMS, such as P, S, and Cl, can be easily determined
      by fs-LI-O-TOFMS. Replicate analyses show that signal variations are 15-35% for
      metallic elements and 25-50% for nonmetallic elements. The results demonstrate
      that fs-LI-O-TOFMS is a simple, rapid, and practical tool for the elemental
      determination of single cells.

PMID- 23544354
TI  - Direct (hetero)arylation: a new tool for polymer chemists.
AB  - The coupling of aryl halides with catalytically activated aryl C-H bonds provides
      a desirable and atom-economical alternative to standard cross-coupling reactions
      for the construction of new C-C bonds. The reaction, termed direct
      (hetero)arylation, is believed to follow a base-assisted, concerted metalation
      deprotonation (CMD) pathway. During this process, carboxylate or carbonate anions
      coordinate to the metal center, typically palladium, in situ and assist in the
      deprotonation transition state. Researchers have employed this methodology with
      numerous arenes and heteroarenes, including substituted benzenes, perfluorinated
      benzenes, and thiophenes. Thiophene substrates have demonstrated high reactivity
      toward C-H bond activation when appropriately substituted with electron-rich
      and/or electron-deficient groups. Because of the pervasive use of thiophenes in
      materials for organic electronics, researchers have used this chemistry to
      modularly prepare conjugated small molecules and, more recently, conjugated
      polymers. Although optimization of reaction conditions such as solvent system,
      phosphine ligand, carboxylate additives, temperature, and time is necessary for
      efficient C-H bond reactivity of each monomer, direct (hetero)arylation
      polymerization (DHAP) can afford high yielding polymeric materials with elevated
      molecular weights. The properties of these materials often rival those of
      polymers prepared by traditional methods. Moreover, DHAP provides a facile means
      for the synthesis of polymers that were previously inaccessible or difficult to
      prepare due to the instability of organometallic monomers. The major downfall of
      direct (hetero)arylation, however, is the lack of C-H bond selectivity,
      particularly for thiophene substrates, which can result in cross-linked material
      during polymerization reactions. Further fine-tuning of reaction conditions such
      as temperature and reaction time may suppress these unwanted side reactions.
      Alternatively, new monomers can be designed where other reactive bonds are
      blocked, either sterically or by substitution with unreactive alkyl or halogen
      groups. In this Account, we illustrate these methods and present examples of DHAP
      reactions that involve the preparation of common homopolymers used in organic
      electronics (P3HT, PEDOT, PProDOT), copolymers formed by activation of electron
      rich (bithiophene, fused bithiophenes) and electron-deficient monomers (TPD,
      1,2,4,5-tetrafluorobenzene, 2,2'-bithiazole). Our group is optimizing these
      reactions and developing ways to make DHAP a common atom-economical synthetic
      tool for polymer chemists.

PMID- 23544355
TI  - Profiles of international archives: Les archives Jean Piaget, University of
      Geneva, Switzerland.
AB  - This research report provides a look behind closed doors at the Jean Piaget
      Archives in Geneva, Switzerland. It situates the potential visitor,
      contextualizes the Archives in its own history, and then describes what scholars
      can expect to find. New details about Piaget's views on Equal Rights and Equal
      Pay are also provided, including a look at how they affected the women who worked
      his factory (esp. Barbel Inhelder). (PsycINFO Database Record (c) 2013 APA, all
      rights reserved).

PMID- 23544356
TI  - Efficacy and toxicity of conventionally fractionated pelvic radiation with a
      hypofractionated simultaneous versus conventionally fractionated sequential boost
      for patients with high-risk prostate cancer.
AB  - PURPOSE: To determine if high-risk prostate cancer responds differently to
      hypofractionation. MATERIAL AND METHODS: One hundred and fifty-seven men with
      NCCN high-risk (T3, PSA > 20, or Gleason >= 8) clinically localized prostate
      cancer treated between 1998 and 2010 met the inclusion criteria for the analysis.
      Eighty-two were treated with conventional WPRT with a conventionally fractionated
      sequential boost to the prostate (cRT), with the prostate receiving 75-77 Gy in
      1.8-2.0 Gy fractions. Seventy-five were treated with pelvic IMRT with a
      hypofractionated simultaneous boost to the prostate (hRT), with the prostate
      receiving 70 Gy in 2.5 Gy fractions. The dose to the pelvic lymph nodes was 45 Gy
      in the cRT group and 50.4 Gy in the hRT group, both at 1.8 Gy per fraction.
      Ninety-two percent received neoadjuvant hormonal ablation therapy, typically
      beginning two months prior to the start of RT. RESULTS: Median follow-up was 6.5
      years for men receiving cRT and 3.7 years for those receiving hRT. The actuarial
      rate of biochemical control at four years was 88% for cRT and 94% for hRT (p =
      0.82). The rates of early rectal and urinary grade >= 2 toxicities were 35% (29
      of 82) and 49% (40 of 82) for the cRT group and 36% (27 of 75) and 44% (33 of 75)
      for the hRT group. The actuarial rate of late grade >= 2 rectal toxicity at four
      years was 25% for the cRT group and 13% for the hRT group (p = 0.037). The rate
      of late grade 3 rectal complications was 4% (3 of 82) for patients receiving cRT
      and 1% (1 of 75) for patients receiving hRT. CONCLUSION: Initial follow-up
      indicates equivalent biochemical control between regimens. Patients receiving hRT
      experienced fewer late rectal complications.

PMID- 23544357
TI  - Androgen deprivation and high-dose radiotherapy for oligometastatic prostate
      cancer patients with less than five regional and/or distant metastases.
AB  - BACKGROUND: Substantial survival may be observed with oligometastatic prostate
      cancer. Combining androgen deprivation (AD) and high-dose external beam
      radiotherapy (RT) to isolated regional or distant lesions may be proposed for
      these patients and the outcome of this strategy is the purpose of the present
      report. MATERIAL AND METHODS: From 2003 to 2010, 50 prostate cancer patients were
      diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM).
      Among the relapsing patients, the recurrence occurred after radical prostatectomy
      in 33 patients and curative RT (+/- AD) in 10 patients. The median age at
      diagnosis was 63 years (range, 48-82). All patients underwent a bone scan and 18F
      choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing
      regional and/or distant nodal and bone and/or visceral metastases in 33 and 17
      patients, respectively. The median delivered effective dose was 64 Gy. All but
      one patient received neo-adjuvant and concomitant AD. RESULTS: After a median
      follow-up of 31 months (range, 9-89) the three-year biochemical relapse-free
      survival (bRFS), clinical failure-free survival, and overall survival rates were
      54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved
      bRFS was found to be significantly associated with the number of OM. The three
      year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A
      normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was
      also correlated with a better three-year bRFS compared to lower doses: 65% vs.
      41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy
      retained statistical significance (HR: 0.37, 95% CI 0.15-0.93). CONCLUSION:
      Oligometastatic patients may be successfully treated with short AD and high-dose
      irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment
      strategy may hypothetically succeed to prolong the failure-free interval between
      two consecutive AD courses.

PMID- 23544358
TI  - Individualized positioning for maximum heart protection during breast
      irradiation.
AB  - BACKGROUND: Prone positioning has been found feasible and appropriate for the
      reduction of radiation exposure of the lungs, but its effects on the heart dose
      remain controversial. Individual anatomical features were sought for the
      selection of optimal treatment positioning. MATERIAL AND METHODS: In 138 left
      sided breast cancer cases awaiting postoperative whole-breast radiotherapy,
      conformal radiotherapy plans were generated in both prone and supine positions.
      RESULTS: The radiation doses to the left anterior descending coronary artery
      (LAD) and heart in the two positions differed individually, and were strongly
      related to the body mass index (BMI). Image fusion of the CT scans revealed that
      prone positioning was detrimental if the heart was situated distant from the
      chest wall in the supine position, but moved to the chest wall in the prone
      position. For characterization of the geography of the heart and the breast, the
      median distance between the LAD and the chest wall (dmedian), and the heart area
      included in the radiation field on a single CT scan at the middle of the heart in
      the supine position (Aheart) proved most appropriate. CONCLUSION: A validated
      statistical model, utilizing the BMI, dmedian and Aheart, permits individualized
      positioning for maximum heart protection.

PMID- 23544360
TI  - Kinetic, electrochemical, and microscopic characterization of the thermophilic,
      anode-respiring bacterium Thermincola ferriacetica.
AB  - Thermincola ferriacetica is a recently isolated thermophilic, dissimilatory
      Fe(III)-reducing, Gram-positive bacterium with capability to generate electrical
      current via anode respiration. Our goals were to determine the maximum rates of
      anode respiration by T. ferriacetica and to perform a detailed microscopic and
      electrochemical characterization of the biofilm anode. T. ferriacetica DSM 14005
      was grown at 60  degrees C on graphite-rod anodes poised at -0.06 V (vs) SHE in
      duplicate microbial electrolysis cells (MECs). The cultures grew rapidly until
      they achieved a sustained current density of 7-8 A m(-2) with only 10 mM
      bicarbonate buffer and an average Coulombic Efficiency (CE) of 93%. Cyclic
      voltammetry performed at maximum current density revealed a Nernst-Monod response
      with a half saturation potential (EKA) of -0.127 V (vs) SHE. Confocal microscopy
      images revealed a thick layer of actively respiring cells of T. ferriacetica (~38
      MUm), which is the first documentation for a gram positive anode respiring
      bacterium (ARB). Scanning electron microscopy showed a well-developed biofilm
      with a very dense network of extracellular appendages similar to Geobacter
      biofilms. The high current densities, a thick biofilm (~38 MUm) with multiple
      layers of active cells, and Nernst-Monod behavior support extracellular electron
      transfer (EET) through a solid conductive matrix - the first such observation for
      Gram-positive bacteria. Operating with a controlled anode potential enabled us to
      grow T. ferriacetica that can use a solid conductive matrix resulting in high
      current densities that are promising for MXC applications.

PMID- 23544359
TI  - Validation of Na,K-ATPase pump function of corneal endothelial cells for corneal
      regenerative medicine.
AB  - Tissue-engineering approaches to cultivate corneal endothelial cells (CECs) or
      induce CECs from stem cells are under investigation for the treatment of
      endothelial dysfunction. Before clinical application, a validation method to
      determine the quality of these cells is required. In this study, we quantified
      the endothelial pump function required for maintaining the corneal thickness
      using rabbit CECs (RCECs) and a human CEC line (B4G12). The potential difference
      of RCECs cultured on a permeable polyester membrane (Snapwell), B4G12 cells on
      Snapwell, or B4G12 cells on a collagen membrane (CM6) was measured by an Ussing
      chamber system, and the effect of different concentrations of ouabain (Na,K
      ATPase specific inhibitor) was obtained. A mathematical equation derived from the
      concentration curve revealed that 2 mM ouabain decreases pump function of RCECs
      to 1.0 mV, and 0.6 mM ouabain decreases pump function of B4G12 on CM6 to 1.0 mV.
      Ouabain injection into the anterior chamber of rabbit eyes at a concentration of
      <2 mM maintained the corneal thickness, while those over 3 mM significantly
      increased the corneal thickness. B4G12 cell sheets transplanted into rabbit eyes
      treated with 0.6 mM ouabain maintained the corneal thickness, while 3.5 mM
      ouabain significantly increased the corneal thickness. Taken together, pump
      function >1.0 mV is required to maintain the corneal thickness. These results can
      be used for standardization of CEC pump function and validation of tissue
      engineered CEC sheets for clinical use.

PMID- 23544361
TI  - NBS-initiated electrophilic phenoxyetherification of olefins.
AB  - A one-pot electrophilic phenoxyetherification using an olefin, a cyclic ether, a
      phenol, and N-bromosuccinimide has been developed. This type of multicomponent
      reaction (MCR) is useful in the synthesis of building blocks that are potentially
      applicable to self-assembly complex construction.

PMID- 23544362
TI  - Cobryketone derived from vitamin B12 via palladium-catalyzed cleavage of the sp3
      sp3 carbon-carbon bond.
AB  - Heptamethyl cobyrinate was transformed into hexamethyl 8-nor-cobyrinate. The
      crucial step involved the synthesis of new, vitamin B12 derived cobryketone via
      palladium-catalyzed cleavage of the sp(3)-sp(3) carbon-carbon bond with the
      liberation of the ketone. The replacement of sp(3) carbon atom with sp(2) (C?O)
      at the 8-position produces a bathochromic shift of all absorption bands and makes
      alpha and beta bands equal as a consequence of the expansion of the existing
      conjugated system of double bonds.

PMID- 23544363
TI  - Adjustment of aortic annulus size during David re-implantation (how to do it).
AB  - Stability of the aortic annulus is a key factor in achieving long-term durability
      of the aortic valve re-implantation. We propose a new method of sub-annular
      fixation of the root prosthesis, enabling post-procedural transesophageal
      echocardiography (TEE)-guided adjustment of the aortic annulus dimensions.

PMID- 23544366
TI  - Comparison of physical activity energy expenditure in Japanese adolescents
      assessed by EW4800P triaxial accelerometry and the doubly labelled water method.
AB  - The present study compared the accuracy of triaxial accelerometry and the doubly
      labelled water (DLW) method for measuring physical activity (PA) in Japanese
      adolescents. A total of sixty adolescents aged 12-15 years were analysed. The
      total energy expenditure (TEE) was measured over 7 d by the DLW method and with
      an EW4800P triaxial accelerometer (Panasonic Corporation). The measured (RMR)(m)
      and predicted RMR (RMR(p)) were 5.7 (SD 0.9) and 6.0 (SD 1.0) MJ/d, respectively.
      TEE measured by the DLW method and accelerometry using RMR(m) or RMR(p) were 11.0
      (SD 2.6), 10.3 (SD 1.9), and 10.7 (SD 2.1) MJ/d, respectively. The PA levels
      (PAL) measured by the DLW method using RMR(m) or RMR(p) were 1.97 (SD 0.31) and
      1.94 (SD 0.31) in subjects who exercised, and 1.85 (SD 0.27) and 1.74 (SD 0.29)
      in subjects who did not exercise. The percentage of body fat correlated
      significantly with the percentage difference between RMR(m) v. RMR(p), TEE, PA
      energy expenditure (PAEE) and PAL using RMR(p), and PAL using RMR(m) assessed by
      the DLW method and accelerometry. The present data showed that while
      accelerometry estimated TEE accurately, it did not provide the precise
      measurement of PAEE and PAL. The error in accelerometry was attributed to the
      prediction error of RMR and assessment in exercise.

PMID- 23544367
TI  - A scalable memetic algorithm for simultaneous instance and feature selection.
AB  - Instance selection is becoming increasingly relevant due to the huge amount of
      data that is constantly produced in many fields of research. At the same time,
      most of the recent pattern recognition problems involve highly complex datasets
      with a large number of possible explanatory variables. For many reasons, this
      abundance of variables significantly harms classification or recognition tasks.
      There are efficiency issues, too, because the speed of many classification
      algorithms is largely improved when the complexity of the data is reduced. One of
      the approaches to address problems that have too many features or instances is
      feature or instance selection, respectively. Although most methods address
      instance and feature selection separately, both problems are interwoven, and
      benefits are expected from facing these two tasks jointly. This paper proposes a
      new memetic algorithm for dealing with many instances and many features
      simultaneously by performing joint instance and feature selection. The proposed
      method performs four different local search procedures with the aim of obtaining
      the most relevant subsets of instances and features to perform an accurate
      classification. A new fitness function is also proposed that enforces instance
      selection but avoids putting too much pressure on removing features. We prove
      experimentally that this fitness function improves the results in terms of
      testing error. Regarding the scalability of the method, an extension of the
      stratification approach is developed for simultaneous instance and feature
      selection. This extension allows the application of the proposed algorithm to
      large datasets. An extensive comparison using 55 medium to large datasets from
      the UCI Machine Learning Repository shows the usefulness of our method.
      Additionally, the method is applied to 30 large problems, with very good results.
      The accuracy of the method for class-imbalanced problems in a set of 40 datasets
      is shown. The usefulness of the method is also tested using decision trees and
      support vector machines as classification methods. 

PMID- 23544368
TI  - Pediatric patients with asthma: a high-risk population for subsequent
      hospitalization.
AB  - OBJECTIVES: Asthma is one of the most common chronic conditions among children
      and is one of the leading causes for pediatric hospitalizations. More evidence is
      needed to clarify the risks of repeat hospitalization and the underlying factors
      contributing to adverse health outcomes among pediatric patients hospitalized
      with asthma. The purpose of this study was to examine the risk of subsequent
      hospitalizations among pediatric patients hospitalized with asthma compared to a
      reference cohort of children hospitalized for all other diagnoses. METHODS: The
      Washington State (WA) Comprehensive Hospital Abstract Reporting System (CHARS)
      was used to obtain data for the study. Data describing 81,946 hospitalized
      pediatric patients admitted from 2004 to 2008 were available. The risk of
      subsequent hospitalization among children admitted for asthma as compared to a
      reference cohort was examined. RESULTS: The asthma cohort had a 33% (HR = 1.33
      [99% confidence interval (CI) 1.21-1.46]; p < .001) increased risk of subsequent
      hospitalization from 2004 to 2008. Children in the asthma cohort under the age of
      13 years demonstrated a significant increased risk of subsequent hospitalization
      as compared to the age-matched reference cohort of children without asthma. Those
      in the asthma cohort who were 3-5 years old demonstrated the highest risk (50%)
      of subsequent hospitalization (HR = 1.50 [99% CI 1.23-1.83]; p < .001).
      CONCLUSIONS: Study results can be utilized in the development of appropriate
      interventions aimed at preventing and reducing hospital admissions, improving
      patient care, decreasing overall costs, and lessening complications among
      pediatric patients with asthma.

PMID- 23544369
TI  - [Environment and health: the lessons of pesticides].

PMID- 23544370
TI  - [Adult cardiomyocytes wake up: a big step towards cardiac regeneration].

PMID- 23544371
TI  - [Contribution to new therapeutics against colorectal cancer: the CReMEC
      initiative].

PMID- 23544372
TI  - [Hyperprolactinemia and infertility: a new physiopathological approach].

PMID- 23544373
TI  - [Thyroid hormone T3 triggers the developmental loss of axonal regenerative
      capacity].

PMID- 23544374
TI  - [Arfaptine-1 controls secretory granule biogenesis].

PMID- 23544375
TI  - [E-selectin, a key regulator of the division of hematopoietic stem cells and
      their resistance to chemotherapy].

PMID- 23544376
TI  - [Control of energy metabolism by natriuretic peptides].

PMID- 23544377
TI  - [FGF9 and FGF20 maintain the stemness of nephron progenitors during kidney
      development].

PMID- 23544378
TI  - [An unexpected repressive role for Scl in the embryonic endothelium].

PMID- 23544379
TI  - [Importance of the location of NMDA glutamate receptors].

PMID- 23544380
TI  - [Blastocyst complementation in pigs allows development of a functional pancreas
      in vivo].

PMID- 23544381
TI  - [Neurotoxicity of pesticides: its relationship with neurodegenerative diseases].
AB  - Several epidemiological studies suggest that pesticides could lead to
      neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Among
      pesticides, insecticides appear more neurotoxic than others but the neurotoxic
      mechanisms leading to adverse health effects remain unclear. The currently used
      pesticides such as rotenone and paraquat could disrupt mitochondrial bioenergetic
      function, reactive oxygen metabolism, redox function and promote alpha-synuclein
      aggregation. In addition, recent studies demonstrate that genetic susceptibility
      to Parkinson's disease could monitor pesticide susceptibility, as demonstrated
      for polymorphisms in pesticide metabolizing enzymes that are involved in
      organophosphorus sensitivity.

PMID- 23544382
TI  - [Renal urinary shear stress: a novel actor in nephropathies].
AB  - The role of fluid shear stress is well established in vascular pathophysiology.
      However, urinary shear stress now also appears as a key mechanism in the
      regulation of renal function. In addition, there is a growing body of evidence
      showing that modified urinary shear stress is involved in the development of
      nephropathies. Therefore we review here the state-of-the-art on the
      pathophysiological roles of urinary shear stress.

PMID- 23544383
TI  - [Migration of melanocytic lineage-derived cells].
AB  - During development, neural crest cells-derived melanoblasts migrate along the
      dorso-lateral axis into the dermis, then cross the basal layer to reach the
      epidermis and differentiate into melanocytes. They finally colonize the hair
      follicles to become resident pigmented cells. Neoplastic transformation converts
      melanocytes into highly invasive melanoma cells, which can adopt two modes of
      interconvertible migration (mesenchymal and amoeboid). Through analysis of the
      coat color phenotype of natural mouse mutants and genetically modified animals,
      many of the genes regulating migration were identified. Deciphering of cell
      membrane protrusions and signaling molecules involved in melanoma cell motility
      was further achieved through 2D and 3D culture systems. Here, we summarize how
      these data allow a better understanding of the complex mechanisms controlling
      migration of normal and pathological cells of the melanocytic lineage.

PMID- 23544384
TI  - [Odontoblast: a key cell involved in the perception of dentinal pain].
AB  - Dentinal sensitivity is a clinical condition daily encountered by practitioners
      and constitutes the symptoms of dentinal hypersensitivity, a common dental pain
      affecting on average 30% of the population. However, the management of this
      pathology is not always effective due to the lack of knowledge particularly
      concerning the means by which dental nociceptive signals are transduced. The
      mechanisms underlying dentin sensitivity still remain unclear probably due to the
      structural and functional complexity of the players including odontoblasts, nerve
      endings and dentinal fluid running in the dentinal tubules. The unique spatial
      situation of odontoblasts, ciliated cells in close relationship with nerve
      terminals, suggests that they could play a pivotal role in the transduction of
      sensory events occurring within the dentin tissue. Our studies have identified
      mechano-thermosensitive transient receptor potential ion channels (TRPV1-4,
      TRPA8, TRPM3, KCa, TREK-1, PC1, PC2) localised on the odontoblastic membrane and
      at the base of the cilium. They could sense temperature variations or movements
      of dentinal fluid within tubules. Moreover, several voltage-gated sodium channels
      confer excitable properties to odontoblasts in response to injection of
      depolarizing currents. In vivo, these channels co-localize with nerve endings at
      the apical pole of odontoblasts, and their expression pattern seems to be
      correlated with the spatial distribution of stretch-activated KCa channels. All
      these data strengthen the hypothesis that odontoblasts could act as sensor cells
      able to transmit nociceptive signals. However, how cells sense signals and how
      the latter are transmitted to axons represent the main issue to be solved.

PMID- 23544385
TI  - [Functions of PALB2 and BRCA2 tumor suppressors in DNA double-strand break
      repair].
AB  - Cancer is now the leading cause of mortality in France. It has been clearly
      demonstrated that mutations in the genetic information is the initiating event of
      cancer. DNA damage such as DNA double-strand breaks leads to genomic instability
      and cancer development. Cells can repair DNA double-strand breaks through several
      mechanisms. Nevertheless, only homologous recombination repair is faithful and
      repairs DNA without creating mutations. Here, we review the roles of PALB2 and
      BRCA2 in homologous recombination and genome stability.

PMID- 23544386
TI  - [Nitric oxide is a major player in plant immune system].
AB  - In animals, nitric oxide (NO) functions as a ubiquitous signaling molecule
      involved in diverse physiological processes such as immunity. Recent studies
      provided evidence that plants challenged by pathogenic microorganisms also
      produce NO. The emerging picture is that NO functions as a signal in plant
      immunity and executes part of its effects through posttranslational protein
      modifications. Notably, the characterization of S-nitrosylated proteins provided
      insights into the molecular mechanisms by which NO exerts its activities. Based
      on these findings, it appears that NO is involved in both the activation and the
      negative control of the signaling pathways related to plant immunity.

PMID- 23544387
TI  - [Cellular and molecular motions: order and disorder].
AB  - Video-microscopy allows monitoring the dynamics of biological components,
      specifically labeled, usually by fluorescent tags such as GFP or quantum dots,
      either at the cellular or at the molecular scale. Reconstructing trajectories
      over time with dedicated algorithms allows to characterize on both scale
      different categories of movement, such as random, linear or confined, and to
      report events such as transient confinements among recorded species and with
      their environment. Single cell or molecule measurements hence provide detailed
      access not only to mean values of relevant descriptors, such as speed or
      interaction duration, but also to the exhaustive distribution of recorded values.

PMID- 23544388
TI  - [Is resilience an epigenetic phenomenon?].
AB  - The likelihood of adult psychiatric problems is increased by childhood trauma,
      particularly so in carriers of certain alleles of certain genes. I discuss here a
      recent paper that sheds light on the mechanism of this effect, showing that
      specific demethylation occurring at the time of the initial trauma persists at
      adulthood and induces an increased reactivity to stress.

PMID- 23544389
TI  - Herpetic (non-cytomegalovirus) retinal infections in patients with the acquired
      immunodeficiency syndrome.
AB  - Human herpes viruses cause significant morbidity in patients with the acquired
      immunodeficiency syndrome. Even after the introduction of highly active anti
      retroviral therapy (HAART), herpes viruses remain the leading causes of blindness
      in AIDS patients. Cytomegalovirus (CMV) retinitis and the closely-related immune
      reconstitution uveitis syndrome are the most common causes of blindness, but
      progressive outer retinal necrosis and acute retinal necrosis due to varicella
      zoster and herpes simplex are also important causes of vision loss. Successful
      treatment of these conditions requires an aggressive approach with multi-drug
      intravenous therapy or repeated intravitreal antiviral injections. Since the rate
      of retinal detachment is alarmingly high despite successful antiviral therapy,
      internists and ophthalmologists must work closely together to recognize and treat
      complications as they arise. Fortunately, Epstein-Barr virus is a rare cause of
      retinal infection and human herpes virus (HHV)-6, HHV-7, and HHV-8 do not appear
      to be primary pathogens. However, increasing evidence suggests that HHV-6 and HHV
      7 play important roles in modulating the immune system and potentiating infection
      by CMV. 

PMID- 23544390
TI  - The evaluation of sexual harassment litigants: reducing discrepancies in the
      diagnosis of posttraumatic stress disorder.
AB  - Relatively few targets of sexual harassment cope with the psychological sequelae
      of their experiences by engaging in litigation. Those who do are often subjected
      to forensic examination to evaluate their history of psychological distress or
      disorder and to determine whether such a condition could be reasonably attributed
      to the alleged harassment, as opposed to some other cause. An unbiased approach
      to such examinations is critical to all parties, as well as to the profession
      itself. This study investigates the relationship between the clinical and
      restructured clinical scales of the Minnesota Multiphasic Personality Inventory
      2, the Trauma Symptom Inventory subscales, the Crime-Related Posttraumatic Stress
      Disorder (CR-PTSD) scale, and an American Psychiatric Association diagnosis (APA,
      Diagnostic and statistical manual of mental disorders; DSM-IV-TR; 4th ed., text
      rev., 2000, Washington, DC, Author) of PTSD in a sample of sexual harassment
      plaintiffs. All measures performed well independently, but together provided
      improved predictive accuracy, suggesting that the use of multiple validated
      measures as well as structured diagnostic interviews may help us better
      understand litigants' experiences and reduce bias in evaluations.

PMID- 23544391
TI  - A prescriptive intergenerational-tension ageism scale: succession, identity, and
      consumption (SIC).
AB  - We introduce a novel ageism scale, focusing on prescriptive beliefs concerning
      potential intergenerational tensions: active, envied resource succession,
      symbolic identity avoidance, and passive, shared-resource consumption (SIC). Four
      studies (2,010 total participants) were used to develop the scale. Exploratory
      factor analysis formed an initial 20-item, 3-factor solution (Study 1). The scale
      converges appropriately with other prejudice measures and diverges from other
      social control measures (Study 2). It diverges from antiyouth ageism (Study 3).
      The Study 4 experiment yielded both predictive and divergent validity apropos
      another ageism measure. Structural equation modeling confirmed model fit across
      all studies. Per an intergenerational-tension focus, younger people consistently
      scored the highest. As generational equity issues intensify, the scale provides a
      contemporary tool for current and future ageism research.

PMID- 23544392
TI  - Evaluating fidelity to the wraparound service model for youth: application of
      item response theory to the Wraparound Fidelity Index.
AB  - The wraparound process is a mechanism for multisystem planning and care
      coordination for youth with serious emotional and behavioral problems. Fidelity
      monitoring is critical to effective implementation of evidence-based practices in
      children's mental health, as it helps ensure that complex interventions like
      wraparound are implemented as intended. The 40-item Wraparound Fidelity Index,
      Version 4 (WFI-4; Bruns, Burchard, Suter, Leverentz-Brady, & Force, 2004) is the
      most frequently used measure of fidelity to the wraparound process, but analysis
      of its psychometric properties is insufficient. An item response theory approach,
      Rasch partial credit models for ordered polytomous data, was used on ratings from
      1,234 facilitators, 1,006 caregivers, and 221 team members, focused on 1,478
      youths (55% male). Results indicated the WFI-4 measured a unidimensional
      construct, with little evidence of item bias and good item and model fit.
      However, the item information curve was skewed, with most people endorsing high
      fidelity responses, and several items had duplicative location estimates. A
      reduced 20-item measure is proposed. Internal reliability estimates for scores
      from this reduced measure were approximately equivalent to the longer measure.
      However, both versions would benefit from additional items located in the highest
      fidelity area of either version of the scale where scores by greater than half of
      our sample fall, but only 3 items are located.

PMID- 23544393
TI  - Rasch analysis of the Outcome Questionnaire with African Americans.
AB  - Effectively diagnosing African Americans' mental health with a single intake
      checklist has posed an unresolved challenge, as most intake checklists were
      developed from White perspectives. In this study, Rasch analysis was used to
      assess the psychometric characteristics of a common measure of clinical distress,
      the Outcome Questionnaire (OQ; Lambert, Lunnen, Umphress, Hansen, & Burlingame,
      1994), for a sample of African American students split into a calibration and
      validation subsample. OQ subscales were first identified and were then held up
      under cross-validation with a second subsample. Rasch analysis of the OQ clearly
      indicated the measure was multidimensional among African American students with 2
      subscales titled Well-Being and Psychological Distress. Our results also
      indicated appropriate response scale use, adequate person separation, strong
      stability across subsamples, and little differential item functioning. Moreover,
      our analysis showed items of the 2 subscales to be well-targeted for African
      American students. However, if subscales were to be revised for African American
      students, some items at the same logit position might be deleted and replaced
      with either very easy or more difficult items or with items at intermediate
      positions to extend and to fill in gaps in construct coverage. Implications for
      theory and research on multicultural mental health scales were discussed.

PMID- 23544394
TI  - Posttraumatic stress disorder in veterans: the utility of the MMPI-2-RF validity
      scales in detecting overreported symptoms.
AB  - The current investigation examined the utility of the overreporting validity
      scales of the Minnesota Multiphasic Personality Inventory-2-Restructured Form
      (MMPI-2-RF; Ben-Porath & Tellegen, 2008) in detecting noncredible reporting of
      symptoms of posttraumatic stress disorder (PTSD) in a sample of disability
      seeking veterans. We also examined the effect of mental health knowledge on the
      utility of these scales by investigating the extent to which these scales
      differentiate between veterans with PTSD and individuals with mental health
      training who were asked to feign symptoms of PTSD on the test. Group differences
      on validity scale scores indicated that these scales were associated with large
      effect sizes for differentiating veterans who overreported from those with PTSD
      and for differentiating between mental health professionals and veterans with
      PTSD. Implications of these results in terms of clinical practice are discussed.

PMID- 23544395
TI  - Structural and incremental validity of the Wechsler Adult Intelligence Scale
      Fourth Edition with a clinical sample.
AB  - Structural and incremental validity of the Wechsler Adult Intelligence Scale
      Fourth Edition (WAIS-IV; Wechsler, 2008a) was examined with a sample of 300
      individuals referred for evaluation at a university-based clinic. Confirmatory
      factor analysis indicated that the WAIS-IV structure was best represented by 4
      first-order factors as well as a general intelligence factor in a direct
      hierarchical model. The general intelligence factor accounted for the most common
      and total variance among the subtests. Incremental validity analyses indicated
      that the Full Scale IQ (FSIQ) generally accounted for medium to large portions of
      academic achievement variance. For all measures of academic achievement, the
      first-order factors combined accounted for significant achievement variance
      beyond that accounted for by the FSIQ, but individual factor index scores
      contributed trivial amounts of achievement variance. Implications for
      interpreting WAIS-IV results are discussed.

PMID- 23544396
TI  - The development and psychometric evaluation of the Smokeless Tobacco Expectancies
      Scale (STES).
AB  - Expectancies regarding the effects of various psychoactive substances are
      important predictors of the initiation and maintenance of substance use. Although
      measures of outcome expectancies exist for several addictive substances, there is
      currently no measure to assess smokeless tobacco (ST) expectancies in an adult
      population. This article presents 2 studies leading to the development and
      psychometric evaluation of the Smokeless Tobacco Expectancies Scale (STES).
      Initially, 155 individuals listed all outcomes they expected to occur if they
      were to use ST products. From these responses, an initial pool of potential STES
      items was identified. The STES was then administered to 2 samples totaling 813
      individuals (265 ST users, 270 cigarette smokers, and 278 nontobacco users). The
      first study included 315 participants who completed a 68-item measure. An
      exploratory factor analysis identified 10 items that may account for individuals'
      ST expectancies. Items loaded on 2 factors: Negative Health Consequences and
      Positive Reinforcement. A confirmatory factor analysis on an independent sample
      (n = 498) supported the proposed factor structure. Furthermore, in both samples,
      the STES accurately discriminated ST users from smokers and nonusers. Findings
      are discussed in terms of the potential uses of the STES for advancing the
      understanding of ST use.

PMID- 23544397
TI  - Estimating the severity of intellectual disability in adults: a Mokken scaling
      analysis of the Learning Disability Screening Questionnaire.
AB  - A Mokken scaling analysis of the learning disability screening questionnaire
      (LDSQ) suggested that, with the exception of 1 item, the scale conforms to the
      properties of a Mokken scale. This has advantages for estimating the severity of
      intellectual disability and inferring the difficulties likely to be experienced
      by an individual for whom there is incomplete information on intellectual and
      adaptive functioning.

PMID- 23544398
TI  - Decision curve analysis for assessing the usefulness of tests for making
      decisions to treat: an application to tests for prodromal psychosis.
AB  - For a test to be considered useful for making treatment decisions, it is
      necessary that making treatment decisions based on the results of the test be a
      preferable strategy to making treatment decisions without the test. Decision
      curve analysis is a framework for assessing when a test would be expected to be
      useful, which integrates evidence of a test's performance characteristics
      (sensitivity and specificity), condition prevalence among at-risk patients, and
      patient preferences for treatment. We describe decision curve analysis generally
      and illustrate its potential through an application to tests for prodromal
      psychosis. Clinical psychosis is often preceded by a prodromal phase, but not all
      those with prodromal symptoms proceed to develop full psychosis. Patients
      identified as at risk for developing psychosis may be considered for proactive
      treatment to mitigate development of clinically defined psychosis. Tests exist to
      help identify those at-risk patients most likely to develop psychosis, but it is
      uncertain when these tests would be considered useful for making proactive
      treatment decisions. We apply decision curve analysis to results from a
      systematic review of studies investigating clinical tests for predicting the
      development of psychosis in at-risk populations, and present resulting decision
      curves that illustrate when the tests may be expected to be useful for making
      proactive treatment decisions.

PMID- 23544399
TI  - The role of personality in the prediction of treatment outcome in pathological
      gamblers: a follow-up study.
AB  - The aim of the present study was to determine which domains in NEO Personality
      Inventory-Revised would predict relapse and dropout in treatment-seeking slot
      machine pathological gamblers after 1-year follow-up. The NEO PI-R was completed
      by 73 consecutive treatment-seeking outpatients before they began an open program
      of individual cognitive-behavioral therapy. Twelve months after starting
      treatment, patients were categorized in groups as abstinent versus relapsed or
      completers versus dropouts. At 1-year follow-up, 29% of patients were abstinent,
      and 48% had completed treatment. Those who had relapsed showed higher significant
      scores on Neuroticism and lower scores on Conscientiousness. The dropout group
      scored significantly higher on Neuroticism and lower on Agreeableness and
      Conscientiousness than the completer group. Low scores on Conscientiousness
      emerged as a significant predictor of relapse; while low scores on
      Conscientiousness and Agreeableness were significant predictors of dropout. It
      seems as if low Conscientiousness could be considered as a predictor of treatment
      failure measured by either relapses or dropouts, whereas, low Agreeableness seems
      to be a prognostic domain specifically for dropouts. Pathological gamblers with
      lower Conscientiousness and lower Agreeableness seem to be at risk of prematurely
      dropping out of treatment. Our findings support the importance of individual
      differences in personality on therapy outcomes. The NEO PI-R may constitute an
      important tool to identify treatment-seeking pathological gamblers who may be at
      risk of relapsing or dropping out of treatment.

PMID- 23544400
TI  - Criterion validity of interpreting scores from multi-informant statistical
      interactions as measures of informant discrepancies in psychological assessments
      of children and adolescents.
AB  - Parents and adolescents often provide discrepant reports of adolescent and family
      behavior. Recent work indicates that scores from indirect measures of
      discrepancies between parent and adolescent reports, namely, statistical
      interactions between reports, longitudinally predict adolescent psychopathology.
      However, no previous work supports the criterion validity of interpreting scores
      from these interactions as indirect measures of informant discrepancies. In a
      community sample of 50 parents and adolescents ages 14-17 years (M = 15.4 years,
      20 males and 30 females), we examined indirect measures of parent-adolescent
      reporting discrepancies, using parent and adolescent reports of parents'
      awareness of adolescents' whereabouts and activities (i.e., parental monitoring).
      We examined these reporting discrepancies in relation to a structured interview
      that directly assesses "discrepant beliefs" or perceived discrepancies between
      parent and adolescent views of daily life topics (e.g., doing chores and
      homework). Greater parent- and adolescent-reported parental monitoring related to
      lower perceived discrepant beliefs. Importantly, the interaction between parental
      monitoring reports provided additional information. Specifically, when
      adolescents provided relatively high parental monitoring reports, we observed
      greater parents' parental monitoring reports relating to lower perceived
      discrepant beliefs, but no such relation when adolescents provided relatively low
      parental monitoring reports. Overall, findings suggest that indirect assessments
      of parent-adolescent discrepancies in reports of parental monitoring relate to
      direct assessments of how parents and adolescents perceive everyday life topics
      differently. These findings have important implications for understanding the
      longitudinal links between informant discrepancies and adolescent
      psychopathology, as well as developing multimethod assessments of informant
      discrepancies in psychological assessments.

PMID- 23544401
TI  - Does cynicism play a role in failure to obtain needed care? Mental health service
      utilization among returning U.S. National Guard soldiers.
AB  - In the present study, the authors examined cynicism, a trait associated with
      mistrust and a misanthropic world view, as an impediment to seeking needed mental
      health services among a group of National Guard Soldiers with diagnoses of
      anxiety, depression, or substance abuse or dependence after a combat deployment.
      On their return from deployment, 40 National Guard soldiers were assessed for
      self-stigma, current distress, attitudes toward mental health care, and
      psychiatric diagnoses. Eight and a half months later, mental health service
      utilization was evaluated. Cynicism assessed prior to deployment was associated
      with lower odds of utilizing mental health services independent of self-stigma
      and negative attitudes toward mental health care. Further, neither self-stigma
      nor attitudes toward mental health care predicted engaging in needed mental
      health care when cynicism was included in the model.

PMID- 23544402
TI  - The Barratt Impulsiveness Scale-11: reassessment of its structure in a community
      sample.
AB  - The Barratt Impulsiveness Scale (Version 11; BIS-11; Patton, Stanford, & Barratt,
      1995) is a gold-standard measure that has been influential in shaping current
      theories of impulse control, and has played a key role in studies of impulsivity
      and its biological, psychological, and behavioral correlates. Psychometric
      research on the structure of the BIS-11, however, has been scant. We therefore
      applied exploratory and confirmatory factor analyses to data collected using the
      BIS-11 in a community sample (N = 691). Our goal was to test 4 theories of the
      BIS-11 structure: (a) a unidimensional model, (b) a 6 correlated first-order
      factor model, (c) a 3 second-order factor model, and (d) a bifactor model. Among
      the problems identified were (a) low or near-zero correlations of some items with
      others; (b) highly redundant content of numerous item pairs; (c) items with
      salient cross-loadings in multidimensional solutions; and, ultimately, (d) poor
      fit to confirmatory models. We conclude that use of the BIS-11 total score as
      reflecting individual differences on a common dimension of impulsivity presents
      challenges in interpretation. Also, the theory that the BIS-11 measures 3
      subdomains of impulsivity (attention, motor, and nonplanning) was not empirically
      supported. A 2-factor model is offered as an alternative multidimensional
      structural representation.

PMID- 23544403
TI  - An independent confirmatory factor analysis of the Wechsler Intelligence Scale
      for Children-fourth Edition (WISC-IV) integrated: what do the process approach
      subtests measure?
AB  - The Wechsler intelligence scale for children--fourth edition (WISC-IV) Integrated
      contains the WISC-IV core and supplemental subtests along with process approach
      subtests designed to facilitate a process-oriented approach to score
      interpretation. The purpose of this study was to examine the extent to which WISC
      IV Integrated subtests measure the constructs they are purported to measure. In
      addition to examining the measurement and scoring model provided in the manual,
      this study also tested hypotheses regarding Cattell-Horn-Carroll abilities that
      might be measured along with other substantive questions regarding the factor
      structure of the WISC-IV Integrated and the nature of abilities measured by
      process approach subtests. Results provide insight regarding the constructs
      measured by these subtests. Many subtests appear to be good to excellent measures
      of psychometric g (i.e., the general factor presumed to cause the positive
      correlation of mental tasks). Other abilities measured by subtests are described.
      For some subtests, the majority of variance is not accounted for by theoretical
      constructs included in the scoring model. Modifications made to remove demands
      such as memory recall and verbal expression were found to reduce construct
      irrelevant variance. The WISC-IV Integrated subtests appear to measure similar
      constructs across ages 6-16, although strict factorial invariance was not
      supported.

PMID- 23544404
TI  - Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of
      mouse splenocytes: a DNA microarray analysis.
AB  - Lactic acid bacteria confer a variety of health benefits. Here, we investigate
      the mechanisms by which Lactobacillus brevis KB290 (KB290) enhances cell-mediated
      cytotoxic activity. Female BALB/c mice aged 9 weeks were fed a diet containing
      KB290 (3 * 10(9) colony-forming units/g) or starch for 1 d. The resulting
      cytotoxic activity of splenocytes against YAC-1 cells was measured using flow
      cytometry and analysed for gene expression using DNA microarray technology. KB290
      enhanced the cell-mediated cytotoxic activity of splenocytes. DNA microarray
      analysis identified 327 up-regulated and 347 down-regulated genes that
      characterised the KB290 diet group. The up-regulated genes were significantly
      enriched in Gene Ontology terms related to immunity, and, especially, a positive
      regulation of T-cell-mediated cytotoxicity existed among these terms. Almost all
      the genes included in the term encoded major histocompatibility complex (MHC)
      class I molecules involved in the presentation of antigen to CD8(+) cytotoxic T
      cells. Marco and Signr1 specific to marginal zone macrophages (MZM), antigen
      presenting cells, were also up-regulated. Flow cytometric analysis confirmed that
      the proportion of MZM was significantly increased by KB290 ingestion.
      Additionally, the over-represented Kyoto Encyclopedia of Genes and Genomes
      pathways among the up-regulated genes were those for natural killer (NK) cell
      mediated cytotoxicity and antigen processing and presentation. The results for
      the selected genes associated with NK cells and CD8(+) cytotoxic T cells were
      confirmed by quantitative RT-PCR. These results suggest that enhanced cytotoxic
      activity could be caused by the activation of NK cells and/or of CD8(+) cytotoxic
      T cells stimulated via MHC class I presentation.

PMID- 23544405
TI  - Use of diffusion tensor imaging in glioma resection.
AB  - Diffusion tensor imaging (DTI) is increasingly used in the resection of both high
      and low-grade gliomas. Whereas conventional MRI techniques provide only
      anatomical information, DTI offers data on CNS connectivity by enabling
      visualization of important white matter tracts in the brain. Importantly, DTI
      allows neurosurgeons to better guide their surgical approach and resection. Here,
      the authors review basic scientific principles of DTI, include a primer on the
      technology and image acquisition, and outline the modality's evolution as a
      frequently used tool for glioma resection. Current literature supporting its use
      is summarized, highlighting important clinical studies on the application of DTI
      in preoperative planning for glioma resection, preoperative diagnosis, and
      postoperative outcomes. The authors conclude with a review of future directions
      for this technology.

PMID- 23544407
TI  - Letter to the editor: hemostasis.

PMID- 23544406
TI  - Imaging preictal hemodynamic changes in neocortical epilepsy.
AB  - OBJECT: The ability to predict seizure occurrence is extremely important to
      trigger abortive therapies and to warn patients and their caregivers. Optical
      imaging of hemodynamic parameters such as blood flow, blood volume, and tissue
      and hemoglobin oxygenation has already been shown to successfully localize
      epileptic events with high spatial and temporal resolution. The ability to
      actually predict seizure occurrence using hemodynamic parameters is less well
      explored. METHODS: In this article, the authors critically review data from the
      literature on neocortical epilepsy and optical imaging, and they discuss the
      preictal hemodynamic changes and their application in neurosurgery. RESULTS:
      Recent optical mapping studies have demonstrated preictal hemodynamic changes in
      both human and animal neocortex. CONCLUSIONS: Optical measurements of blood flow
      and oxygenation may become increasingly important for predicting and localizing
      epileptic events. The ability to successfully predict ictal onsets may be useful
      to trigger closed-loop abortive therapies.

PMID- 23544408
TI  - The role of advanced neuroimaging in intracerebral hemorrhage.
AB  - In this report, the authors sought to summarize existing literature to provide an
      overview of the currently available techniques and to critically assess the
      evidence for or against their application in intracerebral hemorrhage (ICH) for
      management, prognostication, and research. Functional imaging in ICH represents a
      potential major step forward in the ability of physicians to assess patients
      suffering from this devastating illness due to the advantages over standing
      imaging modalities focused on general tissue structure alone, but its use is
      highly controversial due to the relative paucity of literature and the lack of
      consolidation of the predominantly small data sets that are currently in
      existence. Current data support that diffusion tensor imaging and tractography,
      diffusion-perfusion weighted MRI techniques, and functional MRI all possess major
      potential in the areas of highlighting motor deficits, motor recovery, and
      network reorganization. Novel clinical studies designed to objectively assess the
      value of each of these modalities on a wider scale in conjunction with other
      methods of investigation and management will allow for their rapid incorporation
      into standard practice.

PMID- 23544409
TI  - Navigated transcranial magnetic stimulation for mapping the motor cortex in
      patients with rolandic brain tumors.
AB  - OBJECT: Navigated transcranial magnetic stimulation (nTMS) is a novel technology
      in the field of neurosurgery for noninvasive delineation of cortical functional
      topography. This study addresses the spatial accuracy and clinical usefulness of
      nTMS in brain tumor surgery in or near the motor cortex based on a systematic
      review of observational studies. METHODS: A systematic search retrieved 11
      reports published up to October 2012 in which adult patients were examined with
      nTMS prior to surgery. Quality criteria consisted of documentation of the
      influence of nTMS brain mapping on clinical decision making in a standardized
      prospective manner and/or performance of intraoperative direct electrical
      stimulation (DES) and comparison with nTMS results. Cross-observational
      assessment of nTMS accuracy was established by calculating a weighted mean
      distance between nTMS and DES. RESULTS: All studies reviewed in this article
      concluded that nTMS correlated well with the "gold standard" of DES. The mean
      distance between motor cortex identified on nTMS and DES by using the mean
      distance in 81 patients described in 6 quantitatively evaluated studies was 6.18
      mm. The nTMS results changed the surgical strategy based on anatomical imaging
      alone in 25.3% of all patients, based on the data obtained in 87 patients in 2
      studies. CONCLUSIONS: The nTMS technique spatially correlates well with the gold
      standard of DES. Its functional information benefits surgical decision making and
      changes the treatment strategy in one-fourth of cases.

PMID- 23544410
TI  - Integration of functional neuronavigation and intraoperative MRI in surgery for
      drug-resistant extratemporal epilepsy close to eloquent brain areas.
AB  - OBJECT: The authors performed a retrospective study to assess the impact of
      functional neuronavigation and intraoperative MRI (iMRI) on surgery of
      extratemporal epileptogenic lesions on postsurgical morbidity and seizure
      control. METHODS: Twenty-five patients (14 females and 11 males) underwent
      extratemporal resections for drug-resistant epilepsy close to speech/motor brain
      areas or adjacent to white matter tracts. The mean age at surgery was 34 years
      (range 12-67 years). The preoperative mean disease duration was 13.2 years. To
      avoid awake craniotomy, cortical motor-sensory representation was mapped during
      preoperative evaluation in 14 patients and speech representation was mapped in 15
      patients using functional MRI. In addition, visualization of the pyramidal tract
      was performed in 11 patients, of the arcuate fascicle in 7 patients, and of the
      visual tract in 6 patients using diffusion tensor imaging. The mean minimum
      distance of tailored resection between the eloquent brain areas was 5.6 mm.
      During surgery, blood oxygen level-dependent imaging and diffusion tensor imaging
      data were integrated into neuronavigation and displayed through the operating
      microscope. The postoperative mean follow-up was 44.2 months. RESULTS: In 20% of
      these patients, further intraoperative resection was performed because of
      intraoperatively documented residual lesions according to iMRI findings. At the
      end of resection, the final iMRI scans confirmed achievement of total resection
      of the putative epileptogenic lesion in all patients. Postoperatively, transient
      complications and permanent complications were observed in 20% and 12% of
      patients, respectively. Favorable postoperative seizure control (Engel Classes I
      and II) was achieved in 84% and seizure freedom in 72% of these consecutive
      surgical patients. CONCLUSIONS: By using functional neuronavigation and iMRI for
      treatment of epileptogenic brain lesions, the authors achieved a maximum extent
      of resection despite the lesions' proximity to eloquent brain cortex and fiber
      tracts in all cases. The authors' results underline possible benefits of this
      technique leading to a favorable seizure outcome with acceptable neurological
      deficit rates in difficult-to-treat extratemporal epilepsy.

PMID- 23544411
TI  - Integration of functional neuroimaging in CyberKnife radiosurgery: feasibility
      and dosimetric results.
AB  - OBJECT: The integration of state-of-the-art neuroimaging into treatment planning
      may increase the therapeutic potential of stereotactic radiosurgery. Functional
      neuroimaging, including functional MRI, navigated brain stimulation, and
      diffusion tensor imaging-based tractography, may guide the orientation of
      radiation beams to decrease the dose to critical cortical and subcortical areas.
      The authors describe their method of integrating functional neuroimaging
      technology into radiosurgical treatment planning using the CyberKnife
      radiosurgery system. METHODS: The records of all patients who had undergone
      radiosurgery for brain lesions at the CyberKnife Center of the University of
      Messina, Italy, between July 2010 and July 2012 were analyzed. Among patients
      with brain lesions in critical areas, treatment planning with the integration of
      functional neuroimaging was performed in 25 patients. Morphological and
      functional imaging data sets were coregistered using the Multiplan dedicated
      treatment planning system. Treatment planning was initially based on
      morphological data; radiation dose distribution was then corrected in relation to
      the functionally relevant cortical and subcortical areas. The change in radiation
      dose distribution was then calculated. RESULTS: The data sets could be easily and
      reliably integrated into the Cyberknife treatment planning. Using an inverse
      planning algorithm, the authors achieved an average 17% reduction in the
      radiation dose to functional areas. Further gain in terms of dose sparing
      compromised other important treatment parameters, including target coverage,
      conformality index, and number of monitor units. No neurological deficit due to
      radiation was recorded at the short-term follow-up. CONCLUSIONS: Radiosurgery
      treatments rely on the quality of neuroimaging. The integration of functional
      data allows a reduction in radiation doses to functional organs at risk,
      including critical cortical areas, subcortical tracts, and vascular structures.
      The relative simplicity of integrating functional neuroimaging into radiosurgery
      warrants further research to implement, standardize, and identify the limits of
      this procedure.

PMID- 23544412
TI  - Association of functional magnetic resonance imaging indices with postoperative
      language outcomes in patients with primary brain tumors.
AB  - OBJECT: Functional MRI (fMRI) has the potential to be a useful presurgical
      planning tool to treat patients with primary brain tumor. In this study the
      authors retrospectively explored relationships between language-related
      postoperative outcomes in such patients and multiple factors, including measures
      estimated from task fMRI maps (proximity of lesion to functional activation area,
      or lesion-to-activation distance [LAD], and activation-based language
      lateralization, or lateralization index [LI]) used in the clinical setting for
      presurgical planning, as well as other factors such as patient age, patient sex,
      tumor grade, and tumor volume. METHODS: Patient information was drawn from a
      database of patients with brain tumors who had undergone preoperative fMRI-based
      language mapping of the Broca and Wernicke areas. Patients had performed a
      battery of tasks, including word-generation tasks and a text-versus-symbols
      reading task, as part of a clinical fMRI protocol. Individually thresholded task
      fMRI activation maps had been provided for use in the clinical setting. These
      clinical imaging maps were used to retrospectively estimate LAD and LI for the
      Broca and Wernicke areas. RESULTS: There was a relationship between postoperative
      language deficits and the proximity between tumor and Broca area activation (the
      LAD estimate), where shorter LADs were related to the presence of postoperative
      aphasia. Stratification by tumor location further showed that for posterior
      tumors within the temporal and parietal lobes, more bilaterally oriented Broca
      area activation (LI estimate close to 0) and a shorter Wernicke area LAD were
      associated with increased postoperative aphasia. Furthermore, decreasing LAD was
      related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits
      were related to increasing patient age and a shorter Wernicke area LAD.
      CONCLUSIONS: Overall, LAD and LI, as determined using fMRI in the context of
      these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor
      location may influence postoperative deficits, the results indicated that tumor
      proximity to an activation area might also interact with how the language network
      is affected as a whole by the lesion. Although the derivation of LI must be
      further validated in individual patients by using spatially specific statistical
      methods, the current results indicated that fMRI is a useful tool for predicting
      postoperative outcomes in patients with a single brain tumor.

PMID- 23544413
TI  - The role of secondary motor and language cortices in morbidity and mortality: a
      retrospective functional MRI study of surgical planning for patients with
      intracranial tumors.
AB  - OBJECT: Functional MRI (fMRI) is commonly used by neurosurgeons preoperatively to
      identify brain regions associated with essential behaviors, such as language and
      motor abilities. In this study the authors investigated the relationship between
      patient morbidity and mortality and the distance from the tumor border area to
      functional activations in secondary motor and language cortices. METHODS:
      Patients with primary or metastatic brain tumors who underwent preoperative fMRI
      motor and language mapping were selected from a large database of patients with
      tumors. The lesion-to-activation distance (LAD) was measured in each patient
      relative to the supplementary motor area (SMA) for motor tasks and the
      presupplementary motor area (pSMA) for language tasks. The association between
      LAD and the incidence of deficits was investigated using the Fisher exact tests
      of significance. The impact of other variables, including age, handedness, sex,
      and tumor grade, was also investigated. In a subset of patients, logistic
      regression was performed to identify the likelihood of deficits based on the LAD
      to primary and secondary regions. Finally, Mantel-Cox log-rank tests were
      performed to determine whether survival time was significantly related to the LAD
      to secondary motor and language areas. RESULTS: A significant association was
      observed between the LAD to the SMA and the incidence of motor deficits, with the
      percentage of patients with deficits dropping for those in the LAD > 2 cm group.
      The relationship between the LAD to the pSMA and the incidence of language
      deficits was not significant. Logistic regression demonstrated that the LAD to
      primary sensorimotor cortex does affect the incidence of motor deficits, but that
      the LAD to SMA does not. Finally, the authors observed no relationship between
      the LAD to secondary regions and patient mortality rates. CONCLUSIONS: These
      results demonstrate that the LAD to SMA structures does affect morbidity,
      although not to the extent of LAD to primary structures. In addition, motor
      deficits are significantly associated with LAD to secondary structures, but
      language deficits are not. This should be considered by neurosurgeons for patient
      consultation and preoperative planning.

PMID- 23544414
TI  - Characterizing the relationship between functional MRI-derived measures and
      clinical outcomes in patients with vascular lesions.
AB  - OBJECT: Functional MRI (fMRI) has proven to be an effective component of
      pretreatment planning in patients harboring a variety of different brain lesions.
      The authors have recently reported significant relationships concerning distances
      between brain tumor borders and areas of functional activation (lesion-to
      activation distance; LAD) with regard to patient morbidity and mortality. This
      study further examines the relationship between LAD, focusing on a host of
      vascular lesions and pre- and posttreatment morbidity. METHODS: This study
      included a sample population of patients with vascular lesions (n = 106),
      primarily arteriovenous malformations (AVMs) and cavernomas. These patients
      underwent pretreatment fMRI-based motor mapping (n = 72) or language mapping (n =
      84). The impact of LAD and other variables derived from the patient medical
      record were analyzed with respect to functional deficits in terms of morbidity
      (weakness and/or aphasia). RESULTS: In patients with no pretreatment deficits,
      there was trend for a significant relationship between the Wernicke area LAD and
      posttreatment language deficits. In patients with or without pretreatment
      deficits, a trend toward significance was observed between sensorimotor LAD and
      posttreatment motor deficits. Additionally, lesion type (AVMs or cavernomas)
      affected posttreatment deficits, with more patients with cavernomas showing
      posttreatment language deficits than patients with AVMs. However, this difference
      was not observed for posttreatment motor deficits. CONCLUSIONS: These findings
      suggest that the proximity of a vascular lesion to sensorimotor and language
      areas is a relevant parameter in estimating patient prognosis in the
      perioperative period. Additionally, vascular lesion type and existence of
      pretreatment deficits play a significant role in outcomes.

PMID- 23544416
TI  - Introduction: functional imaging.

PMID- 23544415
TI  - Advances in myelin imaging with potential clinical application to pediatric
      imaging.
AB  - White matter development and myelination are critical processes in
      neurodevelopment. Myelinated white matter facilitates the rapid and coordinated
      brain messaging required for higher-order cognitive and behavioral processing.
      Whereas several neurological disorders such as multiple sclerosis are associated
      with gross white matter damage and demyelination, other disorders such as
      epilepsy may involve altered myelination in the efferent or afferent white matter
      pathways adjoining epileptic foci. Current MRI techniques including T1 weighting,
      T2 weighting, FLAIR, diffusion tensor imaging, and MR spectroscopy permit
      visualization of gross white matter abnormalities and evaluation of underlying
      white matter fiber architecture and integrity, but they provide only qualitative
      information regarding myelin content. Quantification of these myelin changes
      could provide new insight into disease severity and prognosis, reveal information
      regarding spatial location of foci or lesions and the associated affected neural
      systems, and create a metric to evaluate treatment efficacy. Multicomponent
      analysis of T1 and T2 relaxation data, or multicomponent relaxometry (MCR), is a
      quantitative imaging technique that is sensitive and specific to myelin content
      alteration. In the past, MCR has been associated with lengthy imaging times, but
      a new, faster MCR technique (mcDESPOT) has made quantitative analysis of myelin
      content more accessible for clinical research applications. The authors briefly
      summarize traditional white matter imaging techniques, describe MCR and mcDESPOT,
      and discuss current and future clinical applications of MCR, with a particular
      focus on pediatric epilepsy.

PMID- 23544417
TI  - Identification of sumoylation activating enzyme 1 inhibitors by structure-based
      virtual screening.
AB  - SUMO activating enzyme 1 (SUMO E1) is responsible for the activation of SUMO in
      the first step of the sumoylation cascade. SUMO E1 is linked to many human
      diseases including cancer, thus making it a potential therapeutic target. There
      are few reported SUMO E1 inhibitors including several natural products. To
      identify small molecule inhibitors of SUMO E1 with better drug-like properties
      for potential therapeutic studies, we have used structure-based virtual screening
      to identify hits from the Maybridge small molecule library for biological assay.
      Our virtual screening protocol involves fast docking of the entire small molecule
      library with rigid protein and ligands followed by redocking of top hits using a
      method that incorporates both ligand and protein flexibility. Subsequently, the
      top-ranking compounds were prioritized using the molecular dynamics simulation
      based binding free energy calculation. Out of 24 compounds that were acquired and
      tested using in vitro sumoylation assay, four of them showed more than 85%
      inhibition of sumoylation with the most active compound showing an IC50 of 14.4
      MUM. A similarity search with the most active compound in the ZINC database has
      identified three more compounds with improved potency. These compounds share a
      common phenyl urea scaffold and have been confirmed to inhibit SUMO E1 by in
      vitro SUMO-1 thioester bond formation assay. Our study suggests that these phenyl
      urea compounds could be used as a starting point for the development of novel
      therapeutic agents.

PMID- 23544418
TI  - Highly stereoselective synthesis of trisubstituted cyclohexanols using a
      guanidine-catalyzed tandem Henry-Michael reaction.
AB  - A highly diastereoselective (dr >99:1) and enantioselective (ee value up to 98%)
      synthesis of trisubstituted cyclohexanols was achieved by using a tandem Henry-
      Michael reaction between nitromethane and 7-oxo-hept-5-enals catalyzed by the
      Misaki-Sugimura guanidine.

PMID- 23544419
TI  - Evaluation of the quality of foods for special diets produced in a school
      catering facility within a HACCP-based approach: a case study.
AB  - A study was carried out to verify the appropriateness of the Hazard Analysis and
      Critical Control Point (HACCP) plan adopted in a school catering facility. To
      that end, the microbiological quality of foods, the correct implementation of
      special diets (lactose- and gluten-free) and the nutritional value of foods were
      assessed. Thirty-six samples of lactose-free and 87 samples of gluten-free
      special diet food preparations were subjected to microbiological, chemical, and
      nutritional analyses. The data collected demonstrate the effectiveness of the
      HACCP plan in reducing the occurrence of microbial and chemical (lactose and
      gluten) cross-contamination. The data obtained from the nutritional analyses
      showed that the dietary intake provided by the meals under study was
      satisfactory. 

PMID- 23544420
TI  - Respiratory complex II: role in cellular physiology and disease.

PMID- 23544421
TI  - Asthma in underserved schoolchildren in Miami, Florida: results of a school- and
      community-based needs assessment.
AB  - OBJECTIVE: Asthma is the most common chronic condition in childhood and
      disproportionately impacts the poorer and ethnic minorities. The objectives of
      the study were to estimate the prevalence of asthma in Miami-Dade County (MDC)
      schoolchildren to aid case-finding and linkage to care. METHODS: We used the CDC
      Youth Risk Behavior Surveillance System (YRBSS) definition of possible asthma
      ("Ever told by a doctor or nurse that they had asthma and still had asthma") and
      analyzed data from four sources. These included the: (1)-MDC YRBSS 2009, (2)-MDC
      Health Connect Asthma Survey of school nurses (>2008), (3)-parents' survey in the
      five HealthConnect survey elementary schools with highest asthma prevalence, and
      (4)-focus group with parents of asthmatic children. RESULTS: (1)-MDC YRBSS data
      showed that 21.3% of high- and 21.4% of middle-school students had been diagnosed
      with possible asthma. Prevalence was the highest in African-American middle
      school girls (26.9%). (2)-HealthConnect survey responders reported that 4.9% of
      the students in 131 MDC schools had possible asthma. Asthma prevalence was higher
      in elementary schools (median = 7.1%) and in low-income MDC zip codes. (3)-Of the
      parent survey responders, 24.9% indicated that their child had possible asthma,
      and 19.2% reported that their children had no usual source of care. (4)-Focus
      group participants reported frequent loss of Medicaid coverage for their
      children, landlords' indifference to the role of poorly maintained housing in
      asthma, and unmet needs regarding knowledge of health system navigation.
      CONCLUSIONS: Asthma may be common in MDC schoolchildren, particularly in poor
      communities. Formidable structural factors limit the caregivers' abilities to
      manage childhood asthma.

PMID- 23544422
TI  - Structure and lateral interaction in mixed monolayers of
      dioctadecyldimethylammonium chloride (DOAC) and stearyl alcohol.
AB  - pi-A isotherms, atomic force microscopy (AFM), and sum frequency generation (SFG)
      vibrational spectroscopy are employed to investigate the molecular structure and
      lateral interactions in mixed monolayers of dioctadecyldimethylammonium chloride
      (DOAC) and stearyl alcohol (SA) at air/water and air/solid interfaces. To avoid
      possible interference between the two molecules in the SFG spectroscopic
      measurements, perprotonated DOAC and perdeuterated SA (dSA) were used. The
      thermodynamic analyses for the pi-A isotherms show that DOAC is miscible with
      dSA. SFG observations reveal that DOAC molecules become conformationally ordered
      as dSA molecules are introduced into the monolayer. AFM observations demonstrate
      coexistence of DOAC-rich and dSA-rich domains in the mixed monolayer with ratios
      different from their initial composition in the subphase. The present study
      suggests that DOAC molecules in the mixed monolayer are condensed by mixing with
      dSA in which the repulsive interactions between positively charged head groups of
      the DOAC molecules are largely reduced along with an increase of van der Waals
      interactions with dSA.

PMID- 23544423
TI  - Essential role of Gli proteins in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common and malignant primary brain
      tumor in adults. Despite several advances, little is known about GBM-specific
      aberrant signalling processes. The hedgehog (Hh) signalling pathway plays a
      central role in GBM pathogenesis and tumor progression. Its activation is
      mediated by sonic hedgehog (Shh), which binds to its receptor patched, PTCH,
      promoting Gli1 activation. Gli1 is a member of the Kruppel family of zinc finger
      transcription factors. Hh/Gli1 axis controls glioma stem cells (GSCs) behaviour,
      which is essential to GBM chemoand radioresistance. Thus, Gli1 modulates the
      expression of stemness genes and the self-renewal of CD133(+) GSCs. The
      activation of Hh/Gli1 in GSCs seems to be dependent on the insulin-like growth
      factor (IGF) signaling, which also contributes to intrinsic and acquired
      resistance of GSCs to temozolomide (TMZ). Beyond Hh signals, Gli1 activity is
      also regulated by several elements, including Ras, Myc, Akt, p53 and PTEN.
      Recently, a truncated variant of Gli1 (tGli1) has been demonstrated to gain the
      ability to regulate expression of genes that are not modulated by Gli1, such as
      the migration/invasion-associated CD24 or the human vascular endothelial growth
      factor-A (VEGF-A), leading to their upregulation. This review will summarize the
      role of Gli proteins in GBM tumorigenesis and their potential impact on GBM
      therapy and treatment resistance.

PMID- 23544424
TI  - Hepatitis C replication inhibitors that target the viral NS4B protein.
AB  - We describe the preclinical development and in vivo efficacy of a novel chemical
      series that inhibits hepatitis C virus replication via direct interaction with
      the viral nonstructural protein 4B (NS4B). Significant potency improvements were
      realized through isosteric modifications to our initial lead 1a. The temptation
      to improve antiviral activity while compromising physicochemical properties was
      tempered by the judicial use of ligand efficiency indices during lead
      optimization. In this manner, compound 1a was transformed into (+)-28a which
      possessed an improved antiviral profile with no increase in molecular weight and
      only a modest elevation in lipophilicity. Additionally, we employed a chimeric
      "humanized" mouse model of HCV infection to demonstrate for the first time that a
      small molecule with high in vitro affinity for NS4B can inhibit viral replication
      in vivo. This successful proof-of-concept study suggests that drugs targeting
      NS4B may represent a viable treatment option for curing HCV infection. 

PMID- 23544425
TI  - Pyrosequencing reveals the key microorganisms involved in sludge alkaline
      fermentation for efficient short-chain fatty acids production.
AB  - Short-chain fatty acids (SCFAs) have been regarded as the excellent carbon source
      of wastewater biological nutrient removal, and sludge alkaline (pH 10)
      fermentation has been reported to achieve highly efficient SCFAs production. In
      this study, the underlying mechanisms for the improved SCFAs production at pH 10
      were investigated by using 454 pyrosequencing and fluorescent in situ
      hybridization (FISH) to analyze the microbial community structures in sludge
      fermentation reactors. It was found that sludge fermentation at pH 10 increased
      the abundances of Pseudomonas sp. and Alcaligenes sp., which were able to excrete
      extracellular proteases and depolymerases, and thus enhanced the hydrolysis of
      insoluble sludge protein and polyhydroxyalkanoates (PHA). Meanwhile, the
      abundance of acid-producing bacteria (such as Clostridium sp.) in the reactor of
      pH 10 was also higher than that of uncontrolled pH, which benefited the
      acidification of soluble organic substrates. Further study indicated that sludge
      fermentation at pH 10 significantly decreased the number of methanogenic archaea,
      resulting in lower SCFAs consumption and lower methane production. Therefore,
      anaerobic sludge fermentation under alkaline conditions increased the abundances
      of bacteria involved in sludge hydrolysis and acidification, and decreased the
      abundance of methanogenic archaea, which favored the competition of bacteria over
      methanogens and resulted in the efficient production of SCFAs.

PMID- 23544426
TI  - Description of the puparium of Protocalliphora nourtevai (Insecta: Diptera:
      Calliphoridae).
AB  - Avian blowflies are obligatory blood-sucking parasite larvae that typically
      pupariate in bird nests. The empty puparia are diagnostically important, as they
      are usually the only evidence for the presence of these parasites in nests.
      Compared to the Nearctic region, very little is known about puparia of Palearctic
      species. Here, we provide the first description of puparia of Protocalliphora
      nourtevai from nests of 2 bird species, namely, Phoenicurus phoenicurus and
      Phoenicurus ochruros from Finland. Puparia possessed irregular pronounced folds
      in the hyper-, meso-, and hypostigmatal region, and no spines were present in the
      entire stigmatal area. There are just 2 distinct spine bands on the ventral
      surface of the puparia. The medial band is absent. There are no plaques or spines
      in the medial region.

PMID- 23544427
TI  - Ortho-phosphinobenzenesulfonate: a superb ligand for palladium-catalyzed
      coordination-insertion copolymerization of polar vinyl monomers.
AB  - Ligands, Lewis bases that coordinate to the metal center in a complex, can
      completely change the catalytic behavior of the metal center. In this Account, we
      summarize new reactions enabled by a single class of ligands, phosphine
      sulfonates (ortho-phosphinobenzenesulfonates). Using their palladium complexes,
      we have developed four unusual reactions, and three of these have produced novel
      types of polymers. In one case, we have produced linear high-molecular weight
      polyethylene, a type of polymer that group 10 metal catalysts do not typically
      produce. Secondly, complexes using these ligands catalyzed the formation of
      linear poly(ethylene-co-polar vinyl monomers). Before the use of phosphine
      sulfonate catalysts, researchers could only produce ethylene/polar monomer
      copolymers that have different branched structures rather than linear ones,
      depending on whether the polymers were produced by a radical polymerization or a
      group 10 metal catalyzed coordination polymerization. Thirdly, these phosphine
      sulfonate catalysts produced nonalternating linear poly(ethylene-co-carbon
      monoxide). Radical polymerization gives ethylene-rich branched ethylene/CO
      copolymers copolymers. Prior to the use of phosphine-sulfonates, all of the metal
      catalyzed processes gave completely alternating ethylene/carbon monoxide
      copolymers. Finally, we produced poly(polar vinyl monomer-alt-carbon monoxide), a
      copolymerization of common polar monomers with carbon monoxide that had not been
      previously reported. Although researchers have often used symmetrical bidentate
      ligands such as diimines for the polymerization catalysis, phosphine-sulfonates
      are unsymmetrical, containing two nonequivalent donor units, a neutral phosphine,
      and an anionic sulfonate. We discuss the features that make this ligand unique.
      In order to understand all of the new reactions facilitated by this special
      ligand, we discuss both the steric effect of the bulky phosphines and electronic
      effects. We provide a unified interpretation of the unique reactivity by
      considering of the net charge and the enhanced back donation in the phosphine
      sulfonate complexes. 

PMID- 23544429
TI  - An examination of the factor structure of the Elemental Psychopathy Assessment.
AB  - The Elemental Psychopathy Assessment (EPA) is a self-report measure designed to
      assess the basic elements of psychopathy from a Five-Factor Model perspective.
      Using two large undergraduate samples, the aim of the current study was to
      further validate this new measure by examining its factor structure and the
      relations of the factors with established psychopathy measures and externalizing
      behaviors (Sample 2 only). Exploratory factor analytic results were highly
      consistent across the two samples and generated a four-factor structure
      characterized by Antagonism, Emotional Stability, Disinhibition, and Narcissism.
      These factors converged as expected with factors from alternative self-report
      conceptualizations of psychopathy and externalizing behaviors. The EPA factors
      also provided incremental validity in the prediction of the alternative
      psychopathy measures and externalizing behaviors above and beyond the other
      psychopathy measures. The stable factor structure and relations with constructs
      relevant to the study of psychopathy provide further support for the EPA as a
      stand-alone, comprehensive assessment of psychopathic personality.

PMID- 23544428
TI  - Sex differences in antisocial personality disorder: results from the National
      Epidemiological Survey on Alcohol and Related Conditions.
AB  - Despite the 3:1 prevalence ratio of men versus women with Antisocial Personality
      Disorder (ASPD), research on sex differences on correlates of ASPD in the general
      population is scarce. The purpose of this study was to examine sex differences in
      childhood and adult adverse events, lifetime psychiatric comorbidity, and
      clinical correlates of DSM-IV ASPD. The sample included 819 men and 407 women
      with DSM-IV ASPD diagnosis. Data were derived from the National Epidemiologic
      Survey on Alcohol and Related Conditions (NESARC) (N = 43,093). Compared to men,
      women with ASPD reported more frequent childhood emotional neglect (AOR = 2.25;
      95% CI: 1.52-3.34) and sexual abuse (AOR = 4.20; 95% CI: 2.78-6.35), any parent
      related adverse event during childhood (e.g., parental substance use disorder)
      (AOR = 2.47; 95% CI: 1.60-3.82), and adverse events during adulthood (AOR = 4.20;
      95% CI: 2.78-6.35). Although women with ASPD present less violent antisocial
      behaviors and higher rates of aggressiveness and irritability (OR = 0.46; 95% CI:
      0.31-0.67), they have higher rates of victimization, greater impairment, and
      lower social support. Our findings suggest increased mental health needs in women
      with ASPD, meriting development of different treatment programs for women and
      men.

PMID- 23544430
TI  - Development of electrolyte-free ozone sensors using boron-doped diamond
      electrodes.
AB  - The electrochemical detection of dissolved ozone in water was examined using
      boron-doped diamond (BDD) electrodes. A well-defined reduction peak was observed
      at ~380 mV for H-terminated BDD, whereas it was observed at ~200 mV in the case
      of O-terminated BDD for an ozone solution in a 0.1 M phosphate buffer solution at
      pH 7. The peak potential for ozone reduction was selective with respect to oxygen
      reduction at both H- and O-terminated BDD electrodes, whereas it occurred at
      approximately the same potential as oxygen reduction at other types of solid
      electrodes, including glassy-carbon, platinum, and gold electrodes. Interference
      from chlorine was not observed in lower concentration than 300 MUM ClO(-).
      Furthermore, in order to apply the detection technique to electrolyte-free media,
      BDD microelectrodes were also used. A linear calibration curve for dissolved
      ozone in water could be achieved between concentrations of 0.49 and 740 MUM, with
      an estimated detection limit (S/N = 3) of 0.185 MUM (S/N = 3). Excellent
      stability was demonstrated for repetitions of these calibration curves performed
      in 3 consecutive days.

PMID- 23544431
TI  - One-pot and regiospecific synthesis of 2,3-disubstituted indoles from 2
      bromoanilides via consecutive palladium-catalyzed Sonogashira coupling,
      amidopalladation, and reductive elimination.
AB  - A practical one-pot and regiospecific three-component process for the synthesis
      of 2,3-disubstituted indoles from 2-bromoanilides was developed via consecutive
      palladium-catalyzed Sonogashira coupling, amidopalladation, and reductive
      elimination.

PMID- 23544432
TI  - Synthesis and pharmacological characterization of 2-(acylamino)thiophene
      derivatives as metabolically stable, orally effective, positive allosteric
      modulators of the GABAB receptor.
AB  - Two recently reported hit compounds, COR627 and COR628, underpinned the
      development of a series of 2-(acylamino)thiophene derivatives. Some of these
      compounds displayed significant activity in vitro as positive allosteric
      modulators of the GABAB receptor by potentiating GTPgammaS stimulation induced by
      GABA at 2.5 and 25 MUM while failing to exhibit intrinsic agonist activity.
      Compounds were also found to be effective in vivo, potentiating baclofen-induced
      sedation/hypnosis in DBA mice when administered either intraperitoneally or
      intragastrically. Although displaying a lower potency in vitro than the reference
      compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in
      vivo: combination of these compounds with a per se nonsedative dose of baclofen
      resulted in shorter onset and longer duration of the loss of righting reflex in
      mice. Test compounds showed cytotoxic effects at concentrations comparable to or
      higher than those of GS39783 or BHF177.

PMID- 23544433
TI  - An efficient synthesis of fluorinated azaheterocycles by aminocyclization of
      alkenes.
AB  - A general and efficient approach to important fluorinated azaheterocycles has
      been developed by incorporating nucleophilic fluorination into alkene
      difunctionalization. This intramolecular aminofluorination transformation of
      alkenes has been achieved via the aminocyclization of reactive unsaturated N
      iodoamines, which can be generated in situ from either unsaturated N-chloramines
      or their amine precursors in a one-pot protocol.

PMID- 23544434
TI  - Survival of patients evaluated for intestinal and multivisceral transplantation -
      the Scandinavian experience.
AB  - OBJECTIVE: The current treatment of choice for patients with intestinal failure
      is parenteral nutrition, whereas medical therapy or resection is preferred for
      patients with neuroendocrine pancreatic tumors (NEPT) along with liver
      metastasis. As the survival of patients undergoing intestinal and multivisceral
      transplantation is improving, the discussion for expansion of treatment options
      has become a subject of debate. The aim was to investigate the outcome for
      patients referred for intestinal and multivisceral transplantation and to
      determine which patient group are the ones most likely to benefit the most from
      transplantation. METHODS: The authors included all patients evaluated for
      intestinal and multivisceral transplantation at the Sahlgrenska University
      Hospital and The Queen Silvia Children's Hospital center between February 1998
      and November 2009. Patients were classified according to proposed treatment
      strategy, and the outcome was evaluated. RESULTS: A total of 43 adults and 19
      children with either intestinal failure or NEPT with liver metastases were
      evaluated for transplantation. Of these patients, 15 adults and 5 children were
      transplanted. Transplantation was lifesaving for most children - all the children
      survived after transplantation, but 70% (4/6) died while awaiting
      transplantation. Among the adult patients with intestinal failure, the survival
      rate for patients considered to be stable on parenteral nutrition was higher than
      the transplanted adult patients. The survival rate of patients with NEPT was
      similar to the results seen among patients transplanted for intestinal failure.
      CONCLUSION: The results confirm the poor prognosis of patients with intestinal
      failure awaiting transplantation and indicate that different transplantation
      criteria may be applied for adults and children, especially when early
      transplantation is the preferred treatment. The role of multivisceral
      transplantation in patients with NEPT remains uncertain.

PMID- 23544435
TI  - Acute effects of second-hand smoke on complete blood count.
AB  - We assessed the acute effects of a 1-h exposure to second-hand smoke (SHS) on
      complete blood count (CBC) markers in a controlled simulated bar/restaurant
      environment. Nineteen adult never-smokers completed a 1-h .exposure to SHS at
      bar/restaurant levels, and a 1-h exposure to normal room air. Blood samples were
      collected at the baseline at 30 min during each exposure, and at 0, 0.5, 1, 2, 3,
      and 4 h after each exposure. The values of white blood cells (WBC) at 1 h (p =
      0.010), 3 h (p = 0.040), and 4 h (p = 0.008) following SHS were significantly
      increased compared with the baseline values. Also, there was a positive
      association between the WBC and cotinine levels (r = 0.28, p = 0.007). A 1-h
      exposure to SHS at bar/restaurant levels significantly increased the WBC for at
      least 4 h following the exposure time. This effect of SHS on WBC has dose
      response characteristics and should be considered to prescribing CBC. 

PMID- 23544436
TI  - Hierarchically structured nanoporous poly(ionic liquid) membranes: facile
      preparation and application in fiber-optic pH sensing.
AB  - Nanoporous polyelectrolyte membranes with hierarchical and unique pore
      architectures can be readily made via electrostatic complexation between
      imidazolium-based poly(ionic liquid)s and poly(acrylic acid) in a variety of
      morphologies. Coating the membrane onto the surface of an optical fiber resulted
      in a device with high pH-sensing performance in terms of the response rate and
      the sensitivity, due to the charge and porous nature of the membrane layer.

PMID- 23544437
TI  - Benzotriazole, benzothiazole, and benzophenone compounds in indoor dust from the
      United States and East Asian countries.
AB  - Organic corrosion inhibitors (OCIs), including ultraviolet light filters, are
      widely used in plastics, rubbers, colorants, and coatings to increase the
      performance of products. Derivatives of benzotriazole (BTR), benzothiazole (BTH),
      and benzophenone (BP) are high-production volume OCIs that have been detected in
      the environment and human tissues. However, knowledge of their occurrence in
      indoor environments, as well as human exposure to them, is still lacking. In this
      study, BTR, BTH, BP and their 12 derivatives were determined in indoor dust for
      the first time. All three groups of OCIs were found in all 158 indoor dust
      samples from the U.S. and three East Asian countries (China, Japan, and Korea).
      The geometric mean (GM) concentration of the sum of six BTRs (GM CSigmaBTRs)
      ranged from 20 to 90 ng/g among the four countries studied, with a maximum
      CSigmaBTRs of ~2000 ng/g found in a dust sample from China. Tolyltriazole was the
      major derivative of BTR measured in dust. GM CSigmaBTHs in indoor dust from the
      four countries ranged from 600 to 2000 ng/g. 2-OH-BTH was the predominant BTH in
      dust from the U.S., Japan, and Korea. GM CSigmaBPs in dust ranged from 80 to 600
      ng/g, with 2-OH-4-MeO-BP and 2,4-2OH-BP, contributing to the majority of ?BP
      concentrations. Based on the concentrations of three types of OCIs in indoor
      dust, human exposure through dust ingestion was calculated. Daily intake of OCIs
      through dust ingestion was higher for people in the U.S., Japan, and Korea than
      in China; the residents in urban China are exposed to higher levels of OCIs via
      dust ingestion than are those in rural China.

PMID- 23544438
TI  - Mitochondrial genome of Cryptocentrus yatsui (Perciformes, Gobioidei) and
      phylogenetic consideration within the genus Cryptocentrus.
AB  - The complete mitochondrial genome (mitogenome) of Cryptocentrus yatsui was first
      determined. The genome was 16,584 bp in length and consisted of 13 protein-coding
      genes, 22 tRNA genes, 2 ribosomal RNA genes, and 2 main noncoding regions (the
      control region and the origin of the light strand replication), the gene
      composition and order of which were similar to most other vertebrates. The
      overall base composition values of the heavy strand are 26.0% for T, 29.9% for C,
      26.4% for A, and 17.7% for G, with a slight A+T bias of 52.4%. To clarify the
      phylogenetic relationships of C. yatsui within the genus Cryptocentrus, 18
      sequences, which were generated from COI region of six species, were used to
      construct the neighbor-joining phylogenetic tree. And we found that C. yatsui was
      rooted with the other Cryptocentrus species and has a distant relationship with
      others. 

PMID- 23544439
TI  - Emerging therapeutic targets in inflammation and allergy drug discovery from
      patent perspective.

PMID- 23544440
TI  - Impact of Saharan dust particles on hospital admissions in Madrid (Spain).
AB  - Saharan dust intrusions make a major contribution to levels of particulate matter
      (PM) present in the atmosphere of large cities. We analysed the impact of
      different PM fractions during periods with and without Saharan dust intrusions,
      using time-series analysis with Poisson regression models, based on:
      concentrations of coarse PM (PM10 and PM10-2.5) and fine PM (PM2.5); and daily
      all-, circulatory- and respiratory-cause hospital admissions. While periods
      without Saharan dust intrusions were marked by a statistically significant
      association between daily mean PM2.5 concentrations and all- and circulatory
      cause hospital admissions, periods with such intrusions saw a significant
      increase in respiratory-cause admissions associated with fractions corresponding
      to PM10 and PM10-2.5. 

PMID- 23544442
TI  - Characterization of gastrins and their receptor in solid human gastric
      adenocarcinomas.
AB  - OBJECTIVE: The gastrin and the gastrin/CCK-B receptor genes are co-expressed in
      several carcinomas. The primary translational product, progastrin, however, is
      processed to several peptides of which only those that are alpha-amidated at
      their C-terminus are receptor ligands. So far, characterization of the progastrin
      derived peptides in gastric cancer has not been reported. The authors therefore
      examined the molecular nature of gastrin and its receptor in human gastric
      carcinomas. MATERIALS AND METHODS: Twenty patients with adenocarcinoma underwent
      partial or total gastrectomy. In samples from each carcinoma, gastrin peptides
      were characterized, using a library of sequence-specific immunoassays. Expression
      was also demonstrated by immunohistochemistry. In addition, the gastrin and
      gastrin/CCK-B receptor gene expression was quantitated using real-time PCR, and
      the receptor protein demonstrated by western blotting. RESULTS: alpha-Amidated
      gastrins were detectable in 16 of 20 carcinomas (median concentration 2.1 pmol/g
      tissue; range 0-386 pmol/g tissue). The tissue concentrations correlated closely
      to the gastrin mRNA contents (r = 0.75, p < 0.0001). Moreover, progastrin and non
      amidated processing intermediates, including glycine-extended gastrins, were
      detected in 19 carcinomas. Immunohistochemistry corroborated gastrin expression
      in carcinoma cells. Chromatography revealed extensive progastrin processing with
      alpha-amidated gastrin-34 and -17 (tyrosyl-sulfated as well as non-sulfated) as
      major products. Finally, gastrin/CCK-B receptor mRNA and protein were detected in
      all tumors. CONCLUSIONS: The results show that the elements for a local loop of
      alpha-amidated gastrins and their receptor are detectable in 80% of human gastric
      adenocarcinomas. Therefore, the results support the contention that locally
      expressed gastrin may be involved in the tumorigenesis of gastric
      adenocarcinomas.

PMID- 23544443
TI  - Dimensional comparison theory.
AB  - Although social comparison (Festinger, 1954) and temporal comparison (Albert,
      1977) theories are well established, dimensional comparison is a largely
      neglected yet influential process in self-evaluation. Dimensional comparison
      entails a single individual comparing his or her ability in a (target) domain
      with his or her ability in a standard domain (e.g., "How good am I in math
      compared with English?"). This article reviews empirical findings from
      introspective, path-analytic, and experimental studies on dimensional
      comparisons, categorized into 3 groups according to whether they address the
      "why," "with what," or "with what effect" question. As the corresponding research
      shows, dimensional comparisons are made in everyday life situations. They impact
      on domain-specific self-evaluations of abilities in both domains: Dimensional
      comparisons reduce self-concept in the worse off domain and increase self-concept
      in the better off domain. The motivational basis for dimensional comparisons,
      their integration with recent social cognitive approaches, and the
      interdependence of dimensional, temporal, and social comparisons are discussed.

PMID- 23544441
TI  - Development of affinity microcolumns for drug-protein binding studies in
      personalized medicine: interactions of sulfonylurea drugs with in vivo glycated
      human serum albumin.
AB  - This report used high-performance affinity microcolumns to examine the changes in
      binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from
      individual patients with diabetes. An immunoextraction approach was developed to
      isolate HSA and glycated HSA from clinical samples, using only 20 MUL of plasma
      or serum and 6-12 nmol of protein to prepare each affinity microcolumn. It was
      found that the affinity microcolumns could be used in either frontal analysis or
      zonal elution studies, which typically required only 4-8 min per run. The
      microcolumns had good stability and allowed data to be obtained for multiple
      drugs and experimental conditions over hundreds of sample application cycles.
      Both the overall binding, as measured by frontal analysis, and site-specific
      interactions, as examined by zonal elution, showed good agreement with previous
      data that had been obtained for in vitro glycated HSA with similar levels of
      modification. It was also possible to directly compare the changes in site
      specific binding that occurred between sulfonylurea drugs or as the level of HSA
      glycation was varied. This method is not limited to clinical samples of glycated
      HSA but could be adapted for work with other modified proteins of interest in
      personalized medicine. 

PMID- 23544444
TI  - Synthesis of a backbone hexasaccharide fragment of the pectic polysaccharide
      rhamnogalacturonan I.
AB  - Synthesis of the fully unprotected hexasaccharide backbone of the pectic
      polysaccharide rhamnogalacturonan I is described. The strategy relies on
      iterative coupling of a common pentenyl disaccharide glycosyl donor followed by a
      late-stage oxidation of the C-6 positions of the galactose residues. The
      disaccharide donor is prepared by an efficient chemoselective armed-disarmed
      coupling of a thiophenyl rhamnoside donor with a pentenyl galactoside acceptor
      bearing the strongly electron-withdrawing pentafluorobenzoyl ester (PFBz)
      protective group.

PMID- 23544445
TI  - Approach for expanding triterpenoid complexity via divergent Norrish-Yang
      photocyclization.
AB  - Triterpenoids comprise a very diverse family of polycyclic molecules that is well
      known to possess a myriad of medicinal properties. Therefore, triterpenoids
      constitute an attractive target for medicinal chemistry and diversity-oriented
      synthesis. Photochemical transformations provide a promising tool for the rapid,
      green, and inexpensive generation of skeletal diversity in the construction of
      natural product-like libraries. With this in mind, we have developed a diversity
      oriented strategy, whereby the parent triterpenoids bryonolic acid and lanosterol
      are converted to the pseudosymmetrical polyketones by sequential allylic
      oxidation and oxidative cleavage of the bridging double bond at the B/C ring
      fusion. The resultant polyketones were hypothesized to undergo divergent Norrish
      Yang cyclization to produce unique 6/4/8-fused triterpenoid analogues. The subtle
      differences between parent triterpenoids led to dramatically different spatial
      arrangements of reactive functionalities. This finding was rationalized through
      conformational analysis to explain unanticipated photoinduced pinacolization, as
      well as the regio- and stereochemical outcome of the desired Norrish-Yang
      cyclization.

PMID- 23544447
TI  - Germinal-center type B-cell classification and clinical characteristics of
      Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases.
AB  - Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease
      with unique clinical characteristics. This study analyzed the germinal-center
      type B-cell (GCB) classification and clinical characteristics of Chinese
      pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen
      University Cancer Center between February 2000 and May 2011, with an age younger
      than 18 years, were included in the analysis. The male/female ratio was 3.47:1.
      The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were
      at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9
      (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS)
      involvement, and 5 (6.6%) had bone involvement. The GCB classification was
      assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19
      (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen
      was administered to 50 patients, and the 4-year event-free survival (EFS) rate
      was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification:
      17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14
      (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our
      data indicate that bone marrow involvement and stage III/IV disease are common in
      Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB
      subtype is similar to that of patients with the non-GCB subtype. The modified B
      NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese
      pediatric patients with DLBCL. 

PMID- 23544448
TI  - A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with
      brentuximab vedotin.
AB  - At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and
      refractory, and therapeutic methods including chemotherapy, radiotherapy, and
      even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed
      of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that
      eradicates tumor cells by binding to the CD30 antigen on their surface. In
      clinical trials, the response rate and complete remission rate of this drug were
      73% and 40%, respectively, for relapsed and refractory HL. Here we report a case
      of CD30-positive relapsed and refractory HL that was treated with brentuximab.
      Before the treatment with brentuximab, the patient underwent chemotherapy,
      radiotherapy, and autologous stem cell transplantation. However, the disease
      continued to progress, affecting multiple organs and prompting symptoms such as
      persistent fever. After the treatment with brentuximab, the patient's condition
      improved. Body temperature returned to normal after 4 days. Lung nodules were
      reduced in size and number after a single course of treatment, and PET/CT showed
      partial remission and complete remission after 3 and 6 courses of treatment,
      respectively. The entire treatment process progressed smoothly, though the
      patient experienced some symptoms due to chemotherapy, including peripheral
      neuritis of the limbs, irritating dry cough, and mild increase in
      aminotransferase. No serious adverse effects were observed. The current general
      condition of the patient is good; the continuous complete remission has amounted
      to 6 months. 

PMID- 23544449
TI  - A modified radiofrequency ablation approach for treating distant lymph node
      metastasis in two patients with late-stage cancer.
AB  - Patients with late-stage cancer commonly have distant lymph node metastasis;
      however, poor health often contraindicates surgical treatment. Although the
      quality of life and overall survival for these patients are low, there is neither
      a consensus nor a guide for treatment. Ablation technique and surrounding tissue
      damage are two possible reasons for limited study of radiofrequency ablation in
      patients with superficial distant lymph node metastasis. Here, we report two
      patients treated successfully with ultrasound-guided radiofrequency ablation for
      superficial distant lymph node metastasis. In these patients, deionized water was
      injected to the surrounding tissues of the lymph node to decrease heat injury.
      Results from these patients suggest that radiofrequency ablation may play an
      important role in the treatment of patients with distant lymph node metastasis. 

PMID- 23544450
TI  - Cancer bioinformatics: detection of chromatin states, SNP-containing motifs, and
      functional enrichment modules.
AB  - In this editorial preface, I briefly review cancer bioinformatics and introduce
      the four articles in this special issue highlighting important applications of
      the field: detection of chromatin states; detection of SNP-containing motifs and
      association with transcription factor-binding sites; improvements in functional
      enrichment modules; and gene association studies on aging and cancer. We expect
      this issue to provide bioinformatics scientists, cancer biologists, and clinical
      doctors with a better understanding of how cancer bioinformatics can be used to
      identify candidate biomarkers and targets and to conduct functional analysis.

PMID- 23544451
TI  - Nudibaccatumone, a trimer comprising a phenylpropanoid and two sesquiterpene
      moieties from Piper nudibaccatum.
AB  - A new complex natural product with a C39 skeleton, named nudibaccatumone, and the
      known sesquiterpenes (+)-spathulenol, (-)-4beta,10alpha-aromadendranediol, and
      ent-T-muurolol, as well as the phenylpropanoid hydroxychavicol, were isolated
      from the aerial parts of Piper nudibaccatum. The structure and absolute
      configuration of nudibaccatumone were elucidated using spectroscopic methods and
      ECD calculations. A 1,8-Michael addition reaction and an intermolecular, inverse
      electron demand Diels-Alder reaction are proposed as the key steps in the
      biosynthesis of nudibaccatumone. 

PMID- 23544452
TI  - A selective turn-on fluorescent sensor for sulfur mustard simulants.
AB  - A fluorescent turn-on sensor for the selective and sensitive detection of sulfur
      mustard simulants in water that uses a metal-ion indicator displacement assay
      (IDA) has been devised. In this IDA approach, a sulfur mustard simulant (the
      analyte) is allowed to react with a dithiol (1) to form a podand (2). This podand
      has a strong affinity to bind with Cd(2+) and displaces an indicator (4
      methylesculetin, ME) from a Cd(2+)-indicator complex (8) to give a turn-on of
      fluorescence. The detection is rapid and highly selective, as we did not observe
      any interference from other electrophiles, even from the oxygen analogue of the
      mustard simulant. The protocol was successfully used for the detection of the
      simulant present on surfaces and in soil samples.

PMID- 23544453
TI  - Mitochondrial DNA of seven Italian sheep breeds shows faint signatures of
      domestication and suggests recent breed formation.
AB  - Italy represented a crucial zone for migration and formation of sheep breeds.
      However, few data on Italian breeds have been published so far. We analysed seven
      Italian sheep breeds using mitochondrial DNA (mtDNA) sequencing to gain
      information on their genetic diversity and history. A 721 bp mtDNA control region
      fragment was amplified and sequenced in a total of 138 samples belonging to seven
      breeds and to Italian mohuflon (Ovis orientalis musimon) to investigate genetic
      diversity and phylogenetic evolution. We retrieved 68 variable sites and 79
      haplotypes. The sheep breeds in our study are quite diverse, and phylogenetic
      analyses resulted in 3.6% of the samples belonging to A, 2.2% to D and 94.2% to B
      mtDNA haplogroups. Principal Component Analysis (PCA) showed a separation of
      breeds on both dimensions. The results of this study provide data on Italian
      breeds, presently scarcely investigated, and contribute to the knowledge of
      Italian sheep breeds and will be useful to the understanding of population
      genetics and breed evolution. 

PMID- 23544454
TI  - In situ treatment with activated carbon reduces bioaccumulation in aquatic food
      chains.
AB  - In situ activated carbon (AC) amendment is a new direction in contaminated
      sediment management, yet its effectiveness and safety have never been tested on
      the level of entire food chains including fish. Here we tested the effects of
      three different AC treatments on hydrophobic organic chemical (HOC)
      concentrations in pore water, benthic invertebrates, zooplankton, and fish
      (Leuciscus idus melanotus). AC treatments were mixing with powdered AC (PAC),
      mixing with granular AC (GAC), and addition-removal of GAC (sediment stripping).
      The AC treatments resulted in a significant decrease in HOC concentrations in
      pore water, benthic invertebrates, zooplankton, macrophytes, and fish. In 6
      months, PAC treatment caused a reduction of accumulation of polychlorobiphenyls
      (PCB) in fish by a factor of 20, bringing pollutant levels below toxic
      thresholds. All AC treatments supported growth of fish, but growth was inhibited
      in the PAC treatment, which was likely explained by reduced nutrient
      concentrations, resulting in lower zooplankton (i.e., food) densities for the
      fish. PAC treatment may be advised for sites where immediate ecosystem protection
      is required. GAC treatment may be equally effective in the longer term and may be
      adequate for vulnerable ecosystems where longer-term protection suffices.

PMID- 23544455
TI  - Parent-specific reciprocity from infancy to adolescence shapes children's social
      competence and dialogical skills.
AB  - Reciprocity - the capacity to engage in social exchange that integrates inputs
      from multiple partners into a unified social event - is a cornerstone of adaptive
      social life that is learned within dyad-specific attachments during an early
      period of neuroplasticity. Yet, very little research traced the expression of
      children's reciprocity with their mother and father in relation to long-term
      outcomes. Guided by evolutionary models, we followed mothers, fathers, and their
      firstborn child longitudinally and observed mother-child and father-child
      reciprocity in infancy, preschool, and adolescence. In preschool, children's
      social competence, aggression, and prosocial behavior were observed at
      kindergarten. In adolescence, children's dialogical skills were assessed during
      positive and conflict interactions with same-sex best friends. Father-child and
      mother-child reciprocity were individually stable, inter-related at each stage,
      and consisted of distinct behavioral components. Structural equation modeling
      indicated that early maternal and paternal reciprocity were each uniquely
      predictive of social competence and lower aggression in preschool, which, in
      turn, shaped dialogical skills in adolescence. Father-adolescent reciprocity
      contributed to the dialogical negotiation of conflict, whereas mother-adolescent
      reciprocity predicted adolescents' dialogical skills during positive exchanges.
      Results highlight the role of parent-child reciprocity in shaping children's
      social collaboration and intimate relationships with non-kin members of their
      social world. 

PMID- 23544457
TI  - Repeatability of the measurement of aortic pulse wave velocity (aPWV) in the
      clinical assessment of arterial stiffness in community-dwelling older patients
      using the Vicorder((r)) device.
AB  - BACKGROUND: Pulse wave velocity measured using the Vicorder((r)) apparatus is a
      non-invasive indicator of arterial stiffness. The objective of this study was to
      assess its repeatability in older patients when used by medical professionals
      with limited experience of the technique. METHODS: Aortic pulse wave velocity
      (aPWV) was measured using the Vicorder((r)) system four times using the
      conventional pathway and twice by adapted pathway in 25 consecutive ambulant
      patients (15 male) after they rested supine for 15 min. A nurse and a doctor
      independently and alternately measured PWV using the same equipment and were
      blinded to their colleague's PWV readings. 'Within' and 'between' observer
      differences were assessed using intra-class correlation coefficients (rI) and 95%
      limits of agreement (95% LoA) derived from Bland-Altman plots. RESULTS: Mean age
      was 79.8 (mean blood pressure [BP] = 133/69, Mean heart rate [HR]: 70.9). Mean
      PWV was 11.73 (Standard Deviation [SD] 2.6-3.6). 'Between' and 'within' observer
      repeatability was high, with rIs ranging from 0.8-0.93. The repeatability index
      for 'between' nurse and doctor measures was slightly lower (rI = 0.88) when an
      adapted cuff measure was used in assessing PWV compared to conventional cuff
      measures (rI = 0.93). Mean PWV readings 'between' observers differed by only
      0.094 (95% CI -0.24 to 1.59). CONCLUSION: When undertaken by operators with
      limited previous technical experience, both 'within' and 'between' observer
      repeatability of PWV measurement was high. This method has the potential to be
      included in the clinical assessment of arterial stiffness in older ambulant
      patients.

PMID- 23544456
TI  - Preparation of thyroid follicular cells for mRNA quantification after
      fluorescence-activated cell sorting.
AB  - We established a novel method to analyze cells collected by fluorescence
      activated cell sorting (FACS) named mRNA quantification after FACS (FACS-mQ) in
      which cells are labeled with a fluorescence dye in a manner that minimizes RNA
      degradation, and then cells sorted by FACS are examined by analyzing their gene
      expression profile. In order to analyze cells using FACS-mQ, it is essential to
      prepare single-cell suspensions without RNA degradation. We found that a new
      tissue preservation medium, ThelioKeepTM, which contains epigallocatechin-3
      gallate (EGCG), was suitable for preservation of thyroid tissues. The aim of this
      study was to establish a cell dispersion method of thyroid follicular cells using
      ThelioKeepTM. We compared the efficiency of cell dispersion between the two
      methods, the conventional cold pre-incubation method and the ThelioKeepTM method;
      then we determined if cells obtained by the ThelioKeepTM method were suitable for
      FACS-mQ analysis. We found that a larger number of cells were recovered using
      ThelioKeepTM than using the conventional cold pre-incubation method. Furthermore,
      cell viability was higher with the ThelioKeepTM method than with the cold pre
      incubation method. Thyroid cells collected by this method were analyzed by FACS
      mQ. A clear shift in flow cytometry analysis was observed when cells were stained
      with an anti-thyroglobulin or anti-thyroid transcription factor-1 antibody. After
      sorting, the same copy number of ACTB mRNA was detected in thyroid cells as in an
      anaplastic carcinoma cell line, 8305C. These findings imply that preparation of
      thyroid cells using the present method is suitable for FACS-mQ analysis.

PMID- 23544458
TI  - Use of limonene in countercurrent chromatography: a green alkane substitute.
AB  - Counter-current chromatography (CCC) is a preparative separation technique
      working with the two liquid phases of a biphasic liquid system. One phase is used
      as the mobile phase when the other, the stationary phase, is held in place by
      centrifugal fields. Limonene is a biorenewable cycloterpene solvent coming from
      orange peel waste. It was evaluated as a possible substitute for heptane in CCC
      separations. The limonene/methanol/water and heptane/methanol/water phase
      diagrams are very similar at room temperature. The double bonds of the limonene
      molecule allows for possible pi-pi interactions with solutes rendering limonene
      slightly more polar than heptane giving small differences in solute partition
      coefficients in the two systems. The 24% higher limonene density is a difference
      with heptane that has major consequences in CCC. The polar and apolar phases of
      the limonene/methanol/water 10/9/1 v/v have -0.025 g/cm(3) density difference
      (lower limonene phase) compared to +0.132 g/cm(3) with heptane (upper heptane
      phase). This precludes the use of this limonene system with hydrodynamic CCC
      columns that need significant density difference to retain a liquid stationary
      phase. It is an advantage with hydrostatic CCC columns because density difference
      is related to the working pressure drop: limonene allows one to work with high
      centrifugal fields and moderate pressure drop. Limonene has the capability to be
      a "green" alternative to petroleum-based solvents in CCC applications. 

PMID- 23544459
TI  - Catalytic asymmetric synthesis of gamma-butenolides by direct vinylogous
      reactions.
AB  - The gamma-butenolide structural motif is a prominent feature in many bioactive
      natural products and drugs. This short review summarizes catalytic asymmetric
      synthesis of gamma-butenolides through direct vinylogous reactions by metal
      complexes and organocatalysts. In light of building chiral gamma-tertiary and
      quaternary carbon centers of butenolides, three synthetic strategies are
      included: 1) the reactions with furanone derivatives as nucleophiles, 2)
      olefination of gamma,gamma- disubstituted butenolides and 3) the reactions by
      using gamma,gamma-disubstituted butenolides as nucleophiles.

PMID- 23544460
TI  - Nickel and cobalt-catalyzed coupling of alkyl halides with alkenes via heck
      reactions and radical conjugate addition.
AB  - Cross-coupling of alkyl halides with alkenes leading to Heck-type and addition
      products is summarized. The development of Heck reaction with aliphatic halides
      although has made significant progress in the past decade and particularly
      recently, it was much less explored in comparison with the aryl halides. The use
      of Ni- and Co-catalyzed protocols allowed efficient Heck coupling of activated
      and unactivated alkenes with 1 degrees , 2 degrees  and 3 degrees  alkyl halides.
      In addition, radical conjugate addition to activated alkenes has become a well
      established method that has led to efficient construction of many natural
      products. The utilization of Ni- and Co-catalyzed strategies would avoid toxic
      tin reagents, and therefore worth exploring. The recent development of Ni- and Co
      catalyzed addition of alkyl halides to alkenes displays much improved reactivity
      and functional group tolerance. In this mini-review, we also attempt to overview
      the mechanisms that are proposed in the reactions, aiming at providing insight
      into the nickel and cobalt-catalyzed coupling of alkyl halides with alkenes.

PMID- 23544461
TI  - Transition metal-catalyzed efficient and green transformations of P(O)-H
      compounds to functional organophosphorus compounds.
AB  - Organophosphorus compounds are of high importance in organic synthesis,
      catalysis, biochemistry, pharmaceuticals, and material science. In this mini
      review, we summarize our recent studies on transition metal-catalyzed green and
      atom efficient transformations of P(O)-H bonds to various versatile
      organophosphorus compounds, including the highly regio- and stereoselective P(O)
      H additions to carbon-carbon unsaturated compounds, asymmetric
      hydrophosphorylation reactions, and dehydrogenative coupling reactions of P(O)-H
      compounds with carbon-H and heteroatom-H compounds. These new reactions provide
      efficient, general and practical ways for the preparation of a variety of well
      defined functional organophosphorus compounds. Mechanistic aspects related to the
      catalytic processes are also discussed.

PMID- 23544462
TI  - Synthesis of selenium compounds by free radical addition based on visible-light
      activated se-se bond cleavage.
AB  - Upon irradiation with near-UV or visible light, organic diselenides undergo
      homolytic cleavage of their selenium-selenium linkage to generate the
      corresponding seleno radicals, which can add to alkynes, allenes, and related
      unsaturated compounds. In the case of alkynes, vicinally diselenated alkenes are
      synthesized successfully. Photoinduced bisselenation of allenes takes place
      selectively at the terminal double bond of allenes. In sharp contrast,
      photoinduced addition of organic diselenides to alkenes is an inefficient
      process. However, combination of diselenides and disulfides under
      photoirradiation conditions results in highly regioselective thioselenation of
      alkenes based on the higher reactivity of thio radicals toward alkenes and the
      higher carbon radical capturing ability of diselenides. Similar conditions can be
      employed with a variety of unsaturated compounds such as alkynes, allenes,
      conjugated dienes, vinylcyclopropanes, and isocyanides. This protocol can also be
      applied to selenotelluration, selenophosphination, and perfluoroalkylselenation
      of unsaturated compounds. The excellent carbon radical capturing ability of
      diselenides makes it possible to attain sequential addition of diselenides to
      several unsaturated compounds by suppression of polymerization of unsaturated
      compounds. When the sequential addition takes place intramolecularly under
      photoirradiation conditions, cyclic products are obtained successfully via a
      radical cyclization process. In addition, novel photoinduced electrocyclic
      reaction of o-alkynylaryl isocyanides with diselenides efficiently affords
      diselenated quinoline derivatives.

PMID- 23544463
TI  - Aqua mediated synthesis of bio-active compounds.
AB  - Recently the aqueous medium has attracted the interest of organic chemists, and
      many. Moreover, in the past 20 years, the drug-discovery process has undergone
      extraordinary changes, and high-throughput biological screening of potential drug
      candidates has led to an ever-increasing demand for novel drug-like compounds.
      Noteworthy advantages were observed during the course of study on aqua mediated
      synthesis of compounds of medicinal importance. The established advantages of
      water as a solvent for reactions are, water is the most abundant and available
      resource on the planet and many biochemical processes occur in aqueous medium.
      This review will focus on describing new developments in the application of water
      in medicinal chemistry for the synthesis of bio-active compounds possessing
      various biological properties.

PMID- 23544464
TI  - Nucleophilic phosphine organocatalysis: a practical synthetic strategy for the
      drug-like nitrogen heterocyclic framework construction.
AB  - Nucleophilic phosphine catalysis has proven to be a practical and powerful
      synthetic strategy in organic chemistry, which can provide easy access to five-,
      six-, seven-, and eight-membered nitrogen heterocyclic compounds. The reaction
      topologies can be controlled by a proper choice of the phosphine catalysts, as
      well as the functionalization of the reaction substrates. In many cases, the
      reactions take place smoothly at room temperature, with high efficiency and atom
      economy. This mini-review presents the recent advances in nucleophilic phosphine
      catalysis for the synthesis of drug-like nitrogen heterocylic compounds. The
      nitrogen heterocyclic compounds with significant biological activities derived
      from the library based on nucleophilic phosphine-catalyzed annulation reactions
      are also highlighted.

PMID- 23544465
TI  - Organic selenium resin in solid phase synthesis and its application in
      constructing medicinally relevant small organic molecules.
AB  - Heterocyclic compounds are of high importance in constructing active drug
      intermediates library. The emergence of solid-phase and combinatorial chemistry
      has led to renewed interest in using organoselenium resins to library drug-like
      production. In this mini review, we summarize the construction of heterocyclic
      compounds libraries such as isoxazoles, oxadiazoles, triazoles, pyrimidines,
      pyrrolines, indolines, benzopyrans, furans etc. using organoselenium resins. And
      it provided efficient and practical ways for the preparation of a variety of well
      defined functional heterocyclic compounds with the advantages of good yields,
      high purity, straightforward operations, broad range and high diversity of the
      products, lack of odor, and good stability of the resins, all of these give
      expression to green chemistry.

PMID- 23544466
TI  - The properties and the use of substituted benzofuroxans in pharmaceutical and
      medicinal chemistry: a comprehensive review.
AB  - Since the synthesis of 4,6-dinitrobenzofuroxan in 1899 by Drost, benzofuroxans
      have attracted particular attention. This peculiar series of compounds exhibit a
      broad spectrum of biological activity including antibacterial, antifungal,
      antileukemic, acaricide and immunodepressive properties. These works embrace a
      period of more than 50 years since the pioneering paper of Gosh and Whitehouse
      and papers in this major field of the heterocyclic chemistry are still published
      in 2013. The review has been built in two independent parts. The first one is
      directly dedicated to the structure of substituted benzofuroxans and will show
      many medicinal applications of these compounds such as nitric oxide-releasing
      abilities, induction of oxidative stress, potent anti-cancer agents, anti-chagas
      agent, target for antiamoebic agent, Ca2+ channel blockers or cytotoxic,
      mutagenic and genotoxic agent... The second part of this review will be in close
      connection with the use of benzofuroxans as synthetic precursors in the
      preparation of new biological compounds such as quinoxaline dioxide,
      benzimidazole and phenazine derivatives. The interaction of substituted
      benzofuroxans with electron rich heterocycles or carbanions is the key step in
      the synthesis of these new biological active compounds. These derivatives can be
      used as cytotoxic drugs, antimycobacterial agent and display anti-malarial,
      antileishmanial and antituberculosis activity. The nature of the substituent
      linked to the carbocyclic ring of benzofuroxan is of primary importance to
      understand the medicinal properties of this family of compounds. For example,
      when benzofuroxans are substituted by electron-releasing substituents, the
      chemical reactivity is transferred from the carbocyclic ring to the furoxan ring.

PMID- 23544467
TI  - Targeting Trypanosoma cruzi platelet-activating factor receptors: scope for the
      development of novel drugs to treat Chagas Disease.
AB  - Chagas Disease (CD), a tropical parasitic disease caused by the flagellate
      protozoan Trypanosoma cruzi, accounts for the highest burden of parasitic
      diseases in the Western hemisphere. Current drug treatments for CD are highly
      toxic and often ineffective, particularly for the chronic stage of the disease, a
      fact that clearly emphasizes the importance of identification/validation of
      molecular targets for the development of new drugs to treat the disease. Here, we
      review in details the evidences that suggest the existence of specific receptors
      for platelet-activating factor (PAF) in T. cruzi, the role of PAF on the control
      of parasite differentiation and the potential of exploring these putative
      receptors as new targets for the chemotherapy of CD.

PMID- 23544468
TI  - Unequivocal role of pyrazine ring in medicinally important compounds: a review.
AB  - Pyrazine is one of the important class of heterocyclic compounds that can be
      obtained naturally or synthesized chemically. Pyrazine ring has got importance in
      exhibiting various biological activities in association with other scaffolds like
      pyrrole, pyrazole, imidazole, triazole, tetrazole, thiophene, oxazole, pyridine,
      piperidine and piperazine. Presence of pyrazine ring as a basic scaffold in
      various clinically used drugs exhibits its importance in drug design. In this
      review, attempt has been made to disclose various therapeutic applications of
      pyrazine derivatives reported during the last decade. 

PMID- 23544469
TI  - Self-assembled potential bio nanocarriers for drug delivery.
AB  - Self-assembled nanocarriers attract increasing attention due to their wide
      application in various practical fields; among them, one of the most focused
      fields is drug delivery. Appropriate selection of surfactant is the basis for
      preparing a successful nanocarrier. Until now, from phospholipid to synthetic
      surfactants, many surfactants have been used to explore a suitable drug delivery
      vehicle for the complex in-vivo environment. Among all, bio surfactants are found
      to be more suitable due to their bio-origin, less-toxicity, biodegradability,
      cheaper rate and above all, their versatile molecular structures. This molecular
      property enables them to self assemble into fascinating structures. Moreover,
      binding DNA, enhancing pH sensitivity and stability allows novelty over their
      synthetic counterparts and phospholipid. This review paper focuses on the
      properties and applications of bio-nano-carriers for drug delivery. Micelle,
      microemulsion, and vesicle are the three nanocarriers which are discussed herein.

PMID- 23544470
TI  - Nutritional and medical applications of spirulina microalgae.
AB  - Spirulina spp. and its processing products are employed in agriculture, food
      industry, pharmaceutics, perfumery and medicine. Spirulina has several
      pharmacological activities such as antimicrobial (including antiviral and
      antibacterial), anticancer, metalloprotective (prevention of heavy-metal
      poisoning against Cd, Pb, Fe, Hg), as well as immunostimulant and antioxidant
      effects due to its rich content of protein, polysaccharide, lipid, essential
      amino and fatty acids, dietary minerals and vitamins. This article serves as an
      overview, introducing the basic biochemical composition of this algae and moves
      to its medical applications. For each application the basic description of
      disease, mechanism of damage, particular content of Spirulina spp. for treatment,
      in vivo and/or in vitro usage, factors associated with therapeutic role, problems
      encountered and advantages are given.

PMID- 23544471
TI  - Exome sequencing in diagnostic evaluation of colorectal cancer predisposition in
      young patients.
AB  - OBJECTIVE: Early-onset colorectal cancer (CRC), defined here as age of onset less
      than 40 years, develops frequently in genetically predisposed individuals. Next
      generation sequencing is an increasingly available option in the diagnostic
      workup of suspected hereditary susceptibility, but little is known about the
      practical feasibility and additional diagnostic yield of the technology in this
      patient group. MATERIALS AND METHODS: We analyzed 38 young CRC patients derived
      from a set of 1514 CRC cases. All 38 tumors had been tested in our laboratory for
      microsatellite instability (MSI), and Sanger sequencing had been used to screen
      for MLH1 and MSH2 mutations in MSI cases. Also, gastrointestinal polyposis had
      been diagnosed clinically and molecularly. Family histories were acquired from
      national registries. If inherited syndromes had not been diagnosed in routine
      diagnostic efforts (n = 23), normal tissue DNA was analyzed for mutations in a
      comprehensive set of high-penetrance genes (MLH1, MSH2, MSH6, PMS2, APC, MUTYH,
      SMAD4, BMPR1A, LKB1/STK11, and PTEN) by exome sequencing. RESULTS: CRC
      predisposition syndromes were confirmed in 42% (16/38) of early-onset CRC
      patients. Hereditary nonpolyposis colorectal cancer was diagnosed in 12 (32%)
      patients, familial adenomatous polyposis in three (7.9%), and juvenile polyposis
      in one (2.6%) patient. Exome sequencing revealed one additional MLH1 mutation.
      Over half of the patients had advanced cancers (Dukes C or D, 61%, 23/38). The
      majority of nonsyndromic patients had unaffected first-degree relatives and
      microsatellite-stable tumors. CONCLUSIONS: Microsatellite instability positivity
      or gastrointestinal polyposis characterized all patients with unambiguous highly
      penetrant germline mutations. In our series, exome sequencing produced little
      added value in diagnosing the underlying predisposition conditions.

PMID- 23544472
TI  - Feedback reduces the metacognitive benefit of tests.
AB  - Testing long-term memory has dual benefits: It enhances learning and it helps
      learners discriminate what they know from what they do not know. The latter
      benefit, known as delayed judgment of learning (dJOL) effect, has been well
      documented, but in prior research participants have not been provided with test
      feedback. Yet when people study they almost universally (a) get feedback and (b)
      judge their learning subsequent to receiving the feedback. Thus, in the first
      three experiments, participants made JOLs following tests with feedback. Adding
      feedback significantly decreased the dJOL effect relative to conditions taking a
      test without receiving feedback. In Experiment 4, participants made decisions
      about which items to restudy (without actually restudying); adding feedback also
      decreased the accuracy of these decisions. These findings suggest that, in
      realistic situations, tests enhance self-monitoring, but not as much as
      previously thought. Judging memory based on prior test performance and ignoring
      the effects of feedback appears to produce an "illusion of not knowing."

PMID- 23544473
TI  - The cost of concreteness: the effect of nonessential information on analogical
      transfer.
AB  - Most theories of analogical transfer focus on similarities between the learning
      and transfer domains, where transfer is more likely between domains that share
      common surface features, similar elements, or common interpretations of
      structure. We suggest that characteristics of the learning instantiation alone
      can give rise to different levels of transfer. We propose that concreteness of
      the learning instantiation can hinder analogical transfer of well-defined
      structured concepts, such as mathematical concepts. We operationalize the term
      concreteness as the amount of information communicated through a specific
      instantiation of a concept. The 5 reported experiments with undergraduate
      students tested the hypothesis by presenting participants with the concept of a
      commutative mathematical group of order 3. The experiments varied the level of
      concreteness of the training instantiation and measured transfer of learning to a
      new instantiation. The results support the hypothesis, demonstrating better
      transfer from more generic instantiations (i.e., ones that communicate minimal
      extraneous information) than from more concrete instantiations. Specifically,
      concreteness was found to create an obstacle to successful structural alignment
      across domains, whereas generic instantiations led to spontaneous structural
      alignment. These findings have important implications for the theory of learning
      and transfer and practical implications for the design of educational material.
      Although some concreteness may activate prior knowledge and perhaps offer a leg
      up in the learning process, this benefit may come at the cost of transfer.

PMID- 23544474
TI  - Mental effort in binary categorization aided by binary cues.
AB  - Binary cueing systems assist in many tasks, often alerting people about potential
      hazards (such as alarms and alerts). We investigate whether cues, besides
      possibly improving decision accuracy, also affect the effort users invest in
      tasks and whether the required effort in tasks affects the responses to cues. We
      developed a novel experimental tool to study binary categorization performance.
      In two experiments, participants decided whether items on a screen were intact or
      faulty, based on the configuration of lighter and darker areas in items. Cues
      were available in half of the experimental blocks, and participants could use
      them in their decisions. Experimental conditions differed in the effort required
      to perform the task, manipulated through the contrast between lighter and darker
      areas (higher contrast vs. lower contrast), and in the validity of cues (medium
      vs. high validity). In the NASA-TLX, participants reported that with highly valid
      cues, they invested less effort in the task, whereas with medium validity cues,
      they invested similar effort as without cues. Responses to the high-validity cues
      were stronger than responses to the medium-validity cues. The required effort in
      the task did not affect the strength of responses to cues. We conclude that the
      invested effort may decrease when cues are available, but users will not rely
      more strongly on cues in more demanding situations to reduce the invested effort.
      We therefore recommend integrating cues into work environments, as they reduce
      users' effort without necessarily leading to overdependence on the cues to reduce
      invested effort.

PMID- 23544475
TI  - The confidence-accuracy relationship for eyewitness identification decisions:
      Effects of exposure duration, retention interval, and divided attention.
AB  - Prior research points to a meaningful confidence-accuracy (CA) relationship for
      positive identification decisions. However, there are theoretical grounds for
      expecting that different aspects of the CA relationship (calibration, resolution,
      and over/underconfidence) might be undermined in some circumstances. This
      research investigated whether the CA relationship for eyewitness identification
      decisions is affected by three, forensically relevant variables: exposure
      duration, retention interval, and divided attention at encoding. In Study 1 (N =
      986), a field experiment, we examined the effects of exposure duration (5 s vs.
      90 s) and retention interval (immediate testing vs. a 1-week delay) on the CA
      relationship. In Study 2 (N = 502), we examined the effects of attention during
      encoding on the CA relationship by reanalyzing data from a laboratory experiment
      in which participants viewed a stimulus video under full or divided attention
      conditions and then attempted to identify two targets from separate lineups.
      Across both studies, all three manipulations affected identification accuracy.
      The central analyses concerned the CA relation for positive identification
      decisions. For the manipulations of exposure duration and retention interval,
      overconfidence was greater in the more difficult conditions (shorter exposure;
      delayed testing) than the easier conditions. Only the exposure duration
      manipulation influenced resolution (which was better for 5 s than 90 s), and only
      the retention interval manipulation affected calibration (which was better for
      immediate testing than delayed testing). In all experimental conditions, accuracy
      and diagnosticity increased with confidence, particularly at the upper end of the
      confidence scale. Implications for theory and forensic settings are discussed.

PMID- 23544476
TI  - Encouraging and clarifying "don't know" responses enhances interview quality.
AB  - Investigative interviewers seek to obtain complete and accurate accounts of
      events from witnesses. Two studies examined the influence of instructions about
      the use of don't know (DK) responses and of clarifying the meanings of DK
      responses on the quality of responding to questioning. Participants watched a
      video, and after a delay (Study 1, 30 min; Study 2, 1 week) were randomized to a
      DK encouraged, DK discouraged, or control group. They then responded to
      answerable and unanswerable questions, after which they clarified the meanings of
      DK responses. Across studies, individuals encouraged to use DK responses answered
      fewer questions and made fewer errors at initial questioning. Discouraged and
      control participants showed similar performance, suggesting that interviewees
      assume that DK responses are not desired unless otherwise instructed. Clarifying
      the meanings of DK responses revealed that a majority of DK responses were
      correct statements about the presence or nonpresence of information in the video.
      The encouraged group showed greater gains in output after clarification while
      maintaining lower errors. Encouragement and clarification of DK responses were
      each associated with higher diagnosticity that substantive answers were in fact
      correct responses to answerable questions. Encouraging DK responses and
      clarifying the meaning of DK responses leads to more accurate reports in response
      to questioning. Encouraging DK responses reduces the tendency to overreport,
      which can reduce the quality of responding. DK responses frequently convey
      different meanings that, if clarified, can lead to useful information about the
      occurrence or nonoccurrence of information.

PMID- 23544477
TI  - The effects of subjective time pressure and individual differences on hypotheses
      generation and action prioritization in police investigations.
AB  - When individuals perceive time pressure, they decrease the generation of
      diagnostic hypotheses and prioritize information. This article examines whether
      individual differences in (a) internal time urgency, (b) experience, and (c)
      fluid mental ability can moderate these effects. Police officers worked through a
      computer-based rape investigative scenario, in which 35 were subjected to a time
      pressure manipulation, with their hypotheses generation and prioritization skills
      compared with a control (n = 41). Group 1 was told they would "get less time to
      complete the scenario compared with other officers," although both groups had
      equal amounts of time. Regression analyses found that time pressure reduced
      hypothesis generation and that individual differences in time urgency moderated
      this effect; individuals who tend to perceive time to pass more slowly than it is
      continued to generate hypotheses despite the presence of time pressure. Time
      pressure also influenced the likelihood of action prioritization at the start of
      the investigation. Time pressure was found to increase action prioritization, but
      only for officers with low time urgency or high fluid ability. Experience had no
      effect on time pressure during the investigative scenario. Implications of these
      findings are discussed.

PMID- 23544478
TI  - Fruits of the ESF Research Networking Programme in Functional Genomics.
AB  - Foreword to the special issue of New Biotechnology comprising review articles by
      former steering committee members to mark the end of the European Science
      Foundation Research Networking Programme in Functional Genomics.

PMID- 23544479
TI  - Not all anger is created equal: the impact of the expresser's culture on the
      social effects of anger in negotiations.
AB  - The influence of culture on the social effects of emotions in negotiations has
      recently gained the attention of researchers, but to date this research has
      focused exclusively on the cultural background of the perceiver of the emotion
      expression. The current research offers the first investigation of how the
      cultural background of the expresser influences negotiation outcomes. On the
      basis of the stereotype that East Asians are emotionally inexpressive and
      European Americans are emotionally expressive, we predicted that anger will have
      a stronger signaling value when East Asians rather than European American
      negotiators express it. Specifically, we predicted that angry East Asian
      negotiators will be perceived as tougher and more threatening and therefore
      elicit great cooperation from counterparts compared with angry European American
      negotiators. Results from 4 negotiation studies supported our predictions. In
      Study 1, angry East Asian negotiators elicited greater cooperation than angry
      European American and Hispanic negotiators. In Study 2, angry East Asian
      negotiators elicited greater cooperation than angry European American ones, but
      emotionally neutral East Asian and European American negotiators elicited the
      same level of cooperation. Study 3 showed that this effect holds for both East
      Asian and European American perceivers and that it is mediated by angry East
      Asian negotiators being perceived as tougher and more threatening than angry
      European American negotiators. Finally, Study 4 demonstrated that the effect
      emerges only when negotiators hold the stereotype of East Asians being
      emotionally inexpressive and European Americans being emotionally expressive. We
      discuss implications for our understanding of culture, emotions, and
      negotiations.

PMID- 23544480
TI  - Idiosyncratic deals and employee outcomes: the mediating roles of social exchange
      and self-enhancement and the moderating role of individualism.
AB  - The majority of studies on idiosyncratic employment arrangements ("i-deals") are
      based on social exchange theory. The authors suggest that self-enhancement
      theory, in addition to social exchange, can be used to explain the effects of i
      deals. Using a multisource sample including 230 employees and 102 supervisors
      from 2 Chinese companies, the authors adopt a 3-wave lagged design to examine the
      mediating roles of social exchange and self-enhancement and the moderating role
      of individualism in the relationships between i-deals and employee outcomes, as
      indicated by proactive behaviors and affective commitment. The results of
      bootstrapping analyses confirm the mediating effects of social exchange and self
      enhancement. In addition, employees with high levels of individualism are more
      receptive to self-enhancement effects; in contrast, employees with low levels of
      individualism are more receptive to social exchange effects.

PMID- 23544481
TI  - The psychological and neurological bases of leader self-complexity and effects on
      adaptive decision-making.
AB  - Complex contexts and environments require leaders to be highly adaptive and to
      adjust their behavioral responses to meet diverse role demands. Such adaptability
      may be contingent upon leaders having requisite complexity to facilitate
      effectiveness across a range of roles. However, there exists little empirical
      understanding of the etiology or basis of leader complexity. To this end, we
      conceptualized a model of leader self-complexity that is inclusive of both the
      mind (the complexity of leaders' self-concepts) and the brain (the
      neuroscientific basis for complex leadership). We derived psychometric and
      neurologically based measures, the latter based on quantitative
      electroencephalogram (qEEG) profiles of leader self-complexity, and tested their
      separate effects on the adaptive decision-making of 103 military leaders. Results
      demonstrated that both measures accounted for unique variance in external ratings
      of adaptive decision-making. We discuss how these findings provide a deeper
      understanding of the latent and dynamic mechanisms that underpin leaders' self
      complexity and their adaptability.

PMID- 23544482
TI  - 8-Amino-BODIPYs: structural variation, solvent-dependent emission, and VT NMR
      spectroscopic properties of 8-R2N-BODIPY.
AB  - New 8-NR2-BODIPYs, R2 = H(i)Pr (3a), H(i)Bu (3b), and Et2 (4), are reported.
      Restricted rotation about the C8-N bond in such molecules has been observed for
      the first time (3a and 3b) and evaluated using VT NMR. The fluorophores 3a and 3b
      are blue emitters, and the efficiency of the emission is closely related to the
      polarity of the solvent, e.g., hexane > toluene > DCM > THF > MeOH > H2O, an
      effect also noted by emission variation in alcohol solvents H(CH2)nOH, n = 1-6.
      In mixed-solvent systems, addition of 10-15% of the more polar solvent results in
      transformation of the emission properties to those of the bulk polar solvent.
      Compound 4 has zero emission in all solvents. The crystal structures of 3a, 3b,
      and 4 are reported, along with that of the parent 8-NH2-BODIPY (2). Compounds 2,
      3a, and 3b exhibit trigonal planar N atoms which are coplanar with the BODIPY
      core; 4 exhibits a very significant distortion that breaks the planarity of the
      extended BODIPY pi system due to the steric impact of the two ethyl groups, an
      observation that explains the lack of emission for 4.

PMID- 23544486
TI  - [Investigation of ultrasound markers in screening fetal trisomy 21].
AB  - OBJECTIVE: To investigate the clinical value of ultrasound markers in screening
      fetal trisomy 21. METHODS: From Jan. 2001 to Dec. 2011, a retrospective study
      about sonographic information of 138 fetuses diagnosed as trisomy 21 was taken in
      the First Affiliated Hospital of Sun Yat-sen University. All fetuses were divided
      into 3 groups: isolated ultrasound markers, non-isolated ultrasound markers, and
      isolated structural malformations or other abnormalities. The relationship
      between trisomy 21 and ultrasound markers as well as structural anomalies or
      other abnormalities was analyzed. RESULTS: Sonographic anomalies were detected in
      132 fetuses (95.7%, 132/138), including ultrasound markers and structural
      malformations or other abnormalities. One hundred and twenty cases (87.0%,
      120/138) had ultrasound markers, 38 (31.7%, 38/120) had one marker and 82 (68.3%,
      82/120) had more than one marker (P < 0.01). Fifty-one fetuses (37.0%, 51/138)
      had isolated ultrasound markers and non-isolated markers were found in 69 fetuses
      (50.0%, 69/138). Only 12 fetuses (8.7%, 12/138) had isolated structural
      malformations or other abnormalities. In 20 fetuses on whom the first-trimester
      ultrasound screening were performed, all had ultrasound markers, 95% (19/20) had
      thickened nuchal translucency and 55% (11/20) had nasal bone hypoplasia. The most
      common ultrasound markers on the second-trimester screening were nasal bone
      hypoplasia, which accounted for 41.9% (52/124) cases, followed by thickened
      nuchal fold (25.0%, 31/124), short femurs and humerus (24.2%, 30/124), echogenic
      intracardiac focus (16.1%, 20/124), mild ventriculomegaly (15.3%, 19/124),
      hyperechoic bowel (12.9%, 16/124), mild renal pyelectasis (12.1%, 15/124).
      Furthermore, the common structural malformations or other abnormalities were as
      follows: cardiac defects (33.1%, 41/124), digestive system (26.6%, 33/124).
      CONCLUSIONS: Ultrasound markers are valuable for screening fetal trisomy 21. The
      fetuses of trisomy 21 usually had more than one ultrasound markers or associated
      with other abnormalities. Combinations of ultrasound markers with the results of
      serum screening and maternal age are necessary for evaluation.

PMID- 23544487
TI  - [Maternal cell contamination of prenatal samples and the potential effects on
      prenatal diagnosis results].
AB  - OBJECTIVE: To assess the frequency and significance of maternal cell
      contamination (MCC) in the invasive prenatal diagnosis, and to analysis the MCC
      effect on prenatal diagnosis results. METHODS: Totally 519 amniotic fluid samples
      from second trimester pregnancy, 57 chorionic villus samples from first trimester
      pregnancy, and 576 blood samples from corresponded pregnant women were collected
      and genotyped by Promega PowerPlex 16 system. MCC was determined according to the
      genotyping results. Karyotypic and molecular diagnosis results were contrasted
      between MCC and non-MCC specimen of the same fetal. RESULTS: MCC presented in
      3.1% (16/519) uncultured amniotic fluid, 1.3% (7/519) cultured amniotic fluid and
      5% (3/57) villi specimens. In the study of fetal karyotype, MCC had no
      significant effect on normal female fetus; but for male fetus and abnormal female
      fetus, there were risk of erroneous results of mosaics. As to molecular
      diagnosis, MCC resulted in more complex effects for the different diagnostic
      methods. And 10%MCC had led to misdiagnosis. CONCLUSIONS: For the prenatal
      cytogenetic tests, MCC should be excluded when there were mosaicism karyotype
      results or suspicious MCC of chorionic villi samples. The effects of MCC had more
      seriously impact on prenatal molecular testing, which suggesting the recommend
      regular identity test for MCC should be carried out.

PMID- 23544488
TI  - [Evaluation of the diagnostic criteria of gestational metabolic syndrome and
      analysis of the risk factors].
AB  - OBJECTIVES: To investigate gestational multiple metabolic abnormalities
      aggregation and diagnostic criteria for gestational metabolic syndrome (GMS), and
      to analyze the risk factors of GMS. METHODS: A cohort study recruiting 309
      pregnant women with preeclampsia, 627 pregnant women with gestational diabetes
      mellitus (GDM) and 1245 normal pregnant women was performed from January 2008 to
      December 2011 in Guangdong Women and Children's Hospital. Information regarding
      age, gestational weeks, basic blood pressure, admission blood pressure, height
      and body mass index(BMI)before pregnancy was recorded. Biochemical indicators
      including fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol
      (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density
      lipoprotein (LDL-C), free fatty acids (FFA) were tested. GMS was diagnosed with
      three or all of the following conditions: (1) overweight and/or obesity before
      pregnancy (BMI >= 25 kg/m(2)); (2) hypertension with blood pressure >= 140/90 mm
      Hg (1 mm Hg = 0.133 kPa); (3) hyperglycemia:diagnosed as GDM; (4) dyslipidemia
      with TG >= 3.23 mmol/L. The incidence of GMS of the three groups were calculated
      and the risk factors were analyzed. RESULTS: (1) The age, gestational weeks,
      basic blood pressure, admission blood pressure, BMI before pregnancy of women
      with preeclampsia and women with GDM were significantly different compared to
      normal women, respectively (P < 0.01). (2) Biochemical indicators of women with
      preeclampsia were as following: FPG (4.6 +/- 1.0) mmol/L, FINS (10.1 +/- 5.6)
      mU/L, TC (6.3 +/- 1.6) mmol/L, TG (3.9 +/- 1.8) mmol/L, HDL-C (1.4 +/- 0.4)
      mmol/L, LDL-C (3.0 +/- 1.0) mmol/L, FFA (0.8 +/- 0.4) mmol/L. And those in women
      with GDM were: FPG (4.7 +/- 0.9) mmol/L, FINS (10.2 +/- 5.8) mU/L, TC (5.7 +/-
      1.3) mmol/L, TG (3.2 +/- 1.1) mmol/L, HDL-C (1.4 +/- 0.4) mmol/L, LDL-C (2.7 +/-
      0.9) mmol/L, FFA (0.6 +/- 0.3) mmol/L. In normal pregnant women they were: FPG
      (4.3 +/- 0.5) mmol/L, FINS (9.0 +/- 4.4) mU/L, TC (5.7 +/- 1.1) mmol/L, TG (2.8
      +/- 1.1) mmol/L, HDL-C (1.5 +/- 0.4) mmol/L, LDL-C (2.9 +/- 0.8) mmol/L, FFA (0.6
      +/- 0.2) mmol/L. Statistic differences were found in preeclampsia and GDM women
      compared to normal women respectively (P < 0.01). (3) The prevalence of GMS in
      preeclampsia group and in GDM group was 26.2% (81/309) and 13.6% (85/627),
      statistically different from that of the control group (0)(P < 0.01). (4)
      Compared to normal women, women with preeclampsia had higher risk of developing
      GMS (OR = 1.62, 95%CI 1.31 - 2.00, P < 0.01). The risk factors were BMI (OR =
      1.29, 95%CI 1.13 - 1.47) and TG (OR = 2.49, 95%CI 1.87 - 3.31). Also, women with
      GDM had higher risk of developing GMS than normal women (OR = 1.27, 95%CI 1.09 -
      1.49, P < 0.01), and the risk factors were BMI (OR = 1.13, 95%CI 1.04 - 1.23) and
      TG (OR = 1.16, 95%CI 1.02 - 1.33). TG was the independent risk factor in both
      preeclampsia women and GDM women (P < 0.01, P < 0.05). HDL-C seemed to have less
      importance in identifying GMS (P > 0.05). CONCLUSIONS: According to the GMS
      diagnostic criteria used in this study, some preeclampsia patients and some GDM
      women had aggregation of multiple metabolic abnormalities including pre-pregnancy
      overweight/obesity, hyperglycemia, high blood pressure and dyslipidemia. TG was
      the independent risk factor for GMS. HDL-C seemed to have less importance in
      identifying GMS.

PMID- 23544489
TI  - [Study on mode of delivery and singleton newborns term birth weight in 3
      hospitals].
AB  - OBJECTIVE: To study newborns weight in singleton term births and the association
      between newborns birth weight and mode of delivery in 3 hospitals. METHODS: From
      Jan. 2005 to Dec. 2009, 13 963 singleton term live neonates born in the
      Department of Obstetrics and Gynecology of Peking University First Hospital (PU
      group), 6519 neonates in Affiliated Hospital of Binzhou Medical College (BMC
      group,) and 8725 neonates in Miyun Hospital Affiliated to Capital Medical
      University, Yanjing Medical College (MYC group) were enrolled in this
      retrospective study. The newborns weight and the rate of macrosomia was
      calculated and compared. Those newborns from PU group and MYC group were divided
      into 2288 neonates at macrosomia group and 20 400 neonates at non-macrosomia
      group, their mode of deliveries were analyzed. RESULTS: (1) The mean neonatal
      birth weight were (3386 +/- 414) g at PU group, (3389 +/- 446) g at BMC group and
      (3445 +/- 449) g at MYC group. Neonates born weight in MYC was significantly
      higher than those from in PU group and BMC group (P = 0.000). Neonates born
      weight in BMC showed higher than those in PU group, which did not reached
      statistical difference (P = 0.638). (2) The incidence of macrosomia were 7.935%
      (1108/13 963) in PU group, 9.802% (639/6519) in BMU group and 13.524% (1180/8725)
      in MYU group. The incidence of macrosomia in MYC group was higher than those in
      PU and BMC group, the incidence of macrosomia in BMC group was higher than that
      in PU group, which reached statistically difference (P = 0.000). (3)The
      proportion of cesarean delivery were 75.306% (1723/2288) at macrosomia group,
      50.765% (10 356/20 400) at non-macrosomia group, which showed statistical
      difference (P = 0.000). CONCLUSIONS: (1) The difference of newborns birth weight
      existed in different administrative level hospital. (2) The risk of cesarean
      delivery due to macrosomia is higher than that of non-macrosomia. (3)
      Obstetricians should pay more attention to nutrition in gestation period to
      lessen the incidence of macrosomia and cesarean section.

PMID- 23544490
TI  - [Effects of plasma from patients with preeclampsia on the proliferation and
      apoptosis of human umbilical vein endothelial cells and its relationship with
      lysophosphatidic acid receptors].
AB  - OBJECTIVES: To investigate the effects of plasma from the patients with
      preeclampsia on proliferation and apoptosis of human umbilical vein endothelial
      cells (HUVEC), and to explore the relationship between cell damage and
      lysophosphatidic acid (LPA) receptors. METHODS: Sixty patients with preeclampsia
      were recruited from October 2011 to June 2012 in the First Affiliated Hospital of
      Zhengzhou University. Among them, thirty cases were defined as the mild
      preeclampsia group and thirty cases were defined as the severe preeclampsia
      group. The other thirty healthy pregnant women were recruited in the healthy
      pregnant women group. The levels of plasma LPA in the three groups were measured.
      The HUVEC were cultured in vitro with plasma from the three groups, and a blank
      control group was set up as well. Proliferation and apoptosis of HUVEC were
      measured by MTT assay and flow cytometry. Immunohistochemistry of biotin
      streptomyces protein peroxidase (SP) method was used to measure the protein
      expression level of Edg 2, 4, 7. RESULTS: (1) The plasma LPA levels in the
      healthy pregnant woman group, mild preeclampsia group and severe preeclampsia
      group were (3.38 +/- 2.08) umol/L, (6.12 +/- 0.22) umol/L, (9.10 +/- 0.17)
      umol/L, respectively. The plasma levels of LPA in patients with preeclampsia were
      significantly higher than that in the healthy pregnant women (P < 0.01). (2) The
      proliferation rate of HUVEC in the mild and severe preeclampsia groups [(65.2 +/-
      2.7)% and (51.9 +/- 2.8)%] were significantly lower than that in the healthy
      pregnant women group and the control group [(84.3 +/- 3.1)% and (100.0 +/- 0.0)%,
      P < 0.01]. (3) The early apoptosis rate, middle-late apoptosis rate and total
      apoptosis rate of HUVEC in the mild and severe preeclampsia groups [total
      apoptosis rate were (30.4 +/- 2.0)% and (43.4 +/- 2.5)%] were significantly
      higher than those in the healthy pregnant women group and the control group
      [total apoptosis rate were (18.6 +/- 1.6)% and (8.0 +/- 1.5)%, P < 0.01]. (4) The
      expression positive rates of Edg 2, 4, 7 proteins in the four groups were as
      following: mild preeclampsia group 83%, 80% and 73%; severe preeclampsia group
      97%, 93% and 90%; healthy pregnant women group 40%, 40% and 37%, and the control
      group 10%, 10% and 7% respectively. The positive rates of HUVEC in the mild and
      severe preeclampsia groups were significantly higher than those in the healthy
      pregnant women group and the control group (P < 0.01). CONCLUSIONS: The plasma of
      patients with preeclampsia could inhibit proliferation and promote apoptosis of
      HUVEC, and induce the expression of Edg 2, 4, 7 proteins. It suggested that the
      increase of lysophosphatidic acid in plasma could be one of the reasons of
      endothelial cell damage in patients with preeclampsia.

PMID- 23544491
TI  - [Modulation of low molecular weight heparin and heparin-binding epidermal growth
      factor on biological functions of human first trimester trophoblast].
AB  - OBJECTIVE: To evaluate the effects of low molecular weight heparin (LMWH) and
      heparin-binding epidermal growth factor (HB-EGF) on the biological function of
      human trophoblast in first trimester. METHODS: From Feb. 2011 to Nov. 2011, the
      trophoblast isolated from human first trimester chorionic villi was cultured in
      vitro. Based on variation of LMWH concentration, the trophoblast was classified
      into 0.025 U/ml group, 0.25 U/ml group, 2.5 U/ml group, 25 U/ml group and 250
      U/ml group. In the mean time, based on treatment of heparin, the trophoblast was
      classified into LMWH group (0.25 U/ml), HB-EGF group (10 ug/L), combination group
      (LMWH at 0.25 U/ml + HB-EGF at 10 ug/L) and add with DMEM as control group. Cell
      proliferation was assessed by the methyl thiazolyl tetrazolium (MTT) test, which
      was showed with the mean absorbance as A value. Cell invasion was measured by
      transwell, which counted the number of cells migrated to the superficies inferia
      of filter membrane. Cell differentiation was assessed by the concentration of hCG
      secretion. RESULTS: Compared with control group, the trophoblast proliferation
      and invasion treated by LMWH at 0.025 U/ml did not show significant difference (P
      > 0.05). When treated by LWMH at 0.25 U/ml and 2.5 U/ml, trophoblast
      proliferation and invasion was increased significantly (P < 0.05). When LMWH at
      25 U/ml and 250 U/ml, it could inhibit trophoblast proliferation and invasion (P
      < 0.05). When compared with A value of 0.44 +/- 0.04 in control group, the
      increased A value were 0.51 +/- 0.05 in LMWH group, 0.56 +/- 0.04 in HB-EGF group
      and 0.69 +/- 0.06 in combination group (P < 0.05). In the transwell test, the
      cell number were 511 +/- 78 in LMWH group, 669 +/- 67 in HB-EGF group and 872 +/-
      64 in combination group, which were significantly higher than 405 +/- 67 in
      control group (P < 0.05), respectively. And the hCG concentration were (7143 +/-
      649) U/L in LMWH group, (11 762 +/- 1059) U/L in HB-EGF group and (11 015 +/-
      1084) U/L in combination group, which showed statistical difference with (8182 +/
      666) U/L in control group (P < 0.05). CONCLUSION: LMWH could modulate
      trophoblast proliferation, invasion, and differentiation. HB-EGF is one of
      important factors involved in effects of LMWH on trophoblast function.

PMID- 23544492
TI  - [Clinicopathological features of 151 cases with abdominal wall endometriosis].
AB  - OBJECTIVE: To investigate clinicopathological features of abdominal wall
      endometriosis (AWE). METHODS: A retrospective study was conducted on 151
      consecutive AWE patients undergoing treatment in Affiliated Obstetrics and
      Gynecology Hospital, Fudan University from January 2003 to December 2010. The
      period of following up was at range of 16 to 97 months. RESULTS: (1) The
      incidence of AWE was 1.96% (166/8469). All 151 AWE cases followed up had previous
      cesarean sections. The period between the previous cesarean section (CS) and the
      onset of symptoms of AWE was 24 months (3 - 192 months). However, the latency was
      not associated with the age at CS, incision site, gestational week at CS,
      duration of lactation, postpartum menstruation recovery, the choice of
      contraceptives and size of AWE (P > 0.05). The duration of disease, defined to be
      the time interval between the onset of symptoms and surgery, was 26 months (2 -
      168 months), which was negatively correlated with the latent period (r = -0.267,
      P < 0.05) and was positively with size of AWE (patients with large-scar
      endometrioma with diameter of lesions >= 3 cm had longer disease duration than
      those with small-scar endometriomas < 3 cm, r = 0.326, P < 0.05). (2) The rate of
      pre-operational ultrasonography detection was 97.4% (147/151). The lesion size
      detected by pre-operative ultrasonography was significantly smaller than that
      measured intraoperatively by palpation (20 mm versus 35 mm, P < 0.05). Moreover,
      only 26.5% (40/151) of AWE patients were found to have deep infiltration by pre
      operative ultrasonography. (3) All patients were managed by surgical treatment to
      completely excise lesions on the abdominal wall. Of all 34 patients (22.5%,
      34/151) took medicine pre-operatively while 57 patients (37.7%, 57/151) taking
      medicine post-operatively. The rate of recurrence was 3.1% (3/96) of cases with
      lesions >= 3 cm, which was significantly lower than 17.8% (8/45) in cases with
      lesion < 3 cm (P < 0.05). (4) After surgery, the symptoms were found to be
      relieved in 93.4% (141/151) of patients. The recurrence rate was 7.8% (11/141)
      while the average recurrent time was (20 +/- 16) months. CONCLUSION: Surgery is
      the main management on AWE. The risk factors associated with recurrence were size
      of lesion and postoperative medication.

PMID- 23544493
TI  - [Relationship of pelvic clinic-pathological features and the pain symptoms in
      ovarian endometrioma].
AB  - OBJECTIVE: To study the relationship between the clinic-pathological features and
      pain symptoms in patients with endometriotic cyst (EM). METHODS: The medical data
      of symptoms, laparoscopy and pathology examination in 416 patients with
      endometriosis were studied retrospectively. All cases were divided into two
      groups on the existence of ovarian endometrioma, including 338 patients in cyst
      group and 78 cases in non-cyst group. The relationship between clinical symptoms
      and location and type of endometrioma was studied. RESULTS: (1) Serum CA125
      level: the level of CA125 were (61 +/- 39) kU/L in cyst group (28 +/- 24) kU/L in
      non-cyst group, which reached statistical difference (P < 0.01). (2) Pathological
      features: among 338 cases, 34.0% of cyst were on left side (115/338), 26.3% were
      right side (89/338), and 39.6% were on both side (134/338). And 95.8% (324/338)
      of cases were combined with the other type of endometriosis, which were 48.5%
      (164/338) with peritoneal endometriosis, 47.3% (160/338) with deep infiltrating
      endometriosis (DIE). In cystic patients, the incidences of endometriosis lesion
      were 13.9% (47/338) on the uterine surface, 38.5% (130/338) on obstruction of cul
      de sac, 40.5% (137/338) on utero-sacral ligament of DIE, which were significantly
      higher than 5.1%, (4/78), 9.0% (7/78) and 28.2% (22/78) in noncyst group. (3)
      Pain symptom: the incidence and degree of dysmenorrhea and dyschezia had no
      statistical difference between two groups (P > 0.05), and the incidence of
      chronic pelvic pain (CPP) of 24.6% (83/338) and dyspareunia of 29.9% (101/338) in
      the cyst group were significantly lower than 35.9% (28/78) and 44.9% (35/78) in
      non-cyst group (P < 0.05). The incidence of dysmenorrheal was 85.1% (114/134) in
      cases with bilateral cyst, which was higher than 74.0% (151/204) in cases with
      single cyst. The incidence of dysmenorrheal and dyschezia in moderate-severe
      adhesion was 89.0% (138/155) and 18.7% (29/155), which was significantly higher
      than 68.8% (126/183) and 8.2% (15/183) in mild adhesion. In the patients cyst
      existed with DIE, the risk of dysmenorrheal, CPP, dyspareunia, and dyschezia were
      obviously raised (OR respectively was 5.17, 3.01, 3.05, 2.75). CONCLUSIONS: The
      endometriotic cyst often co-exists with other type of endometriotic lesions.
      Ovarian endometrioma was associated with lesion localized on uterine surface, cul
      de-sac, sacrum ligament. The risk of all the pain symptoms would be raised when
      the endometriotic cyst co-exit with the DIE lesions. So the treatment for DIE
      lesions was as same important as the endometriotic lesions in order to relieve
      pain symptoms and delay the relapse.

PMID- 23544494
TI  - [Clinical analysis of 44 cases with malignant transformation of ovarian mature
      cystic teratoma].
AB  - OBJECTIVE: To analyze the clinicopathologic characteristics, treatment and
      prognostic factors in malignant transformation of mature cystic teratoma (MCT) of
      ovary. METHODS: The clinical data of 44 patients with MCT from January 1961 to
      June 2009 were reviewed. RESULTS: The median age of the 44 patients was 48 years
      (range, 16 - 84 years). Mean tumor size was (16 +/- 6) cm. Thirty-two cases were
      diagnosed squamous cell carcinoma (73%, 32/44), and 5 of them with the elevated
      level of serumal squamous cell antigen (SCC-Ag). Three of 37 cases (8%, 3/37)
      were identified with malignant transformation in image examinations. Rapid frozen
      section examination and multiple-location biopsy were performed in 8 cases, and 5
      of them were detected with malignant diseases. Twenty-two patients with disease
      confined within the unilateral ovary (10 with intact capsule, and 12 with
      ruptured capsule). Diseases extended extra ovaries in the others 22 patients. The
      median cumulative overall survivals were 126 and 10 months, respectively. The
      difference between the two groups was significant (P < 0.01). Twenty-seven
      patients had no residual tumor after primary surgery. The median cumulative
      overall survivals between the patients with and without residual tumor were 10
      and 84 months respectively, and there were significant difference between two
      groups (P < 0.01). Seven selected patients with malignant disease confined within
      unilateral ovary underwent fertility-sparing surgery, and 2 cases of them had
      successful pregnancies and delivery, while other 4 cases with ruptured capsule
      recurred. CONCLUSIONS: The most common pathology type of malignant transformation
      in mature cystic teratoma of the ovary is squamous cell carcinoma. Comprehensive
      pre-operation image examination and tumor marker level detection might be of
      great help in diagnosis. Tumor extension extraovary and residual tumor after
      surgery are the most significant poor prognostic factors. Early stage patient
      with ruptured capsule should be very discreet to choose fertility-sparing
      surgery.

PMID- 23544495
TI  - [Influence of pertussis toxin on GPER-mediated activation of phosphatidylinositol
      3-kinase/protein kinase B signaling induced by 17beta-estradiol in endometrial
      carcinoma cells].
AB  - OBJECTIVE: To investigate the influence of pertussis toxin (PTX) on G protein
      coupled estrogen receptor (GPER)-mediated activation of phosphatidylinositol 3
      kinase (PI3K)/protein kinase B (Akt) signaling activated by 17beta-estradiol
      (17beta-E2) in endometrial carcinoma cells. METHODS: Expressions of GPER protein
      were detected by immunohistochemical SP method in Ishikawa and HEC-1A cells.
      Changes of levels of GPER, ERalpha and ERbeta protein and the activation of Akt
      protein were observed by western blot in the two cells after they were treated by
      PTX for 30 minutes at different concentrations (0, 0.1, 0.5, 1.0 ug/ml), and then
      co-stimulated with with 1*10(-6) mol/L 17beta-E2 respectively at different time
      (Ishikawa 30 minutes, HEC-1A 15 minutes). RESULTS: (1) Immunohistochemical SP
      method showed that GPER was positive stained in cell cytoplasm of Ishikawa and
      HEC-1A cell. (2) After co-treated with PTX at different concentrations (0, 0.1,
      0.5, 1.0 ug/ml) and 10(-6) mol/L 17beta-E2, in Ishikawa cell, the ratio of p
      Akt/Akt was 0.74 +/- 0.54, 0.34 +/- 0.06, 0.18 +/- 0.03, 0.07 +/- 0.15, the gray
      values of GPER was 0.872 +/- 0.490, 0.395 +/- 0.054, 0.145 +/- 0.014, 0.034 +/-
      0.008, and with increasing concentration of PTX, the ratio of p-Akt/Akt and the
      expression of GPER decreased gradually (P < 0.05), which was most obviously when
      the concentration was 1.0 ug/ml (F = 63.729, P = 0.0001; F = 160.284, P =
      0.0001); ERalpha and ERbeta protein had no significant change among different
      groups (P > 0.05). In HEC-1A cell, the ratio of p-Akt/Akt was 0.73 +/- 0.09, 0.26
      +/- 0.14, 0.11 +/- 0.03, 0, the Gray values of GPER is 0.927 +/- 0.134, 0.485 +/-
      0.022, 0.194 +/- 0.004, 0, and with increasing concentration of PTX, the ratio of
      p-Akt/Akt and the expression of GPER decreased gradually (P < 0.05), which were
      also completely inhibited when the concentration was 1 ug/ml (F = 1039.321, P =
      0.0001; F = 109.646, P = 0.0001), ERalpha protein had no significant differences
      (P > 0.05) among different groups. ERbeta was negatively expressed. CONCLUSION:
      The results proposed that the activation of PI3K/Akt signaling in Ishikawa and
      HEC-1A cells could be inhibited after blocking the role of GPER by PTX.

PMID- 23544496
TI  - Effects of bis(imidazolium) molten salts with different substituents of
      imidazolium cations on the performance of efficient dye-sensitized solar cells.
AB  - Bis(imidazolium) iodides (bis-Im(+)I(-)s) are synthesized with different
      substituents and used as electrolytes in dye-sensitized solar cells (DSSCs).
      Three kinds of low-volatility electrolytes are prepared by using 1,1'-methylene
      bis(3-imidazolium) diiodide (MIDI), 1,1'-methylene bis(3-n-methylimidazolium)
      diiodide (MMIDI), and 1,1'-methylene-bis(3-n-ethylimidazolium) diiodide (MEIDI)
      as the iodide sources. The effects of these substituents on the photovoltaic
      performance of the cells are investigated. It is found that the device shows a
      lower short-circuit photocurrent (Jsc), higher open-voltage (Voc) and fill factor
      (FF) with the increased cation size in electrolyte. These results are explained
      by electrostatic interactions between the solvated Im(+) and the negatively
      charged species. Meanwhile, the explanation is supported by electrochemical
      impedance spectroscopy (EIS), cyclic voltammetry (CV), open circuit voltage decay
      (OCVD), and dark current measurements.

PMID- 23544498
TI  - Nonprecious-metal-assisted photochemical hydrogen production from ortho
      phenylenediamine.
AB  - The combination of o-phenylenediamine (opda), which possesses two proton- and
      electron-pooling capability, with Fe(II) leads to the photochemical hydrogen
      evolution reaction (HER) in THF at room temperature without addition of
      photosensitizers. From the THF solution, the tris(o-phenylenediamine) iron(II)
      complex, [Fe(II)(opda)3](ClO4)2 (1), was isolated as a photoactive species, while
      the deprotonated oxidized species was characterized by X-ray crystallographic
      analysis, electrospray ionization mass spectrometry, and UV-vis NIR spectra.
      Furthermore, the HER is photocatalyzed by hydroquinone, which serves as a H(+)/e(
      ) donor. The present work demonstrates that the use of a metal-bound aromatic
      amine as a H(+)/e(-) pooler opens an alternative strategy for designing
      nonprecious-metal-based molecular photochemical H2 production/storage materials.

PMID- 23544499
TI  - Removal of estrogenic compounds from filtered secondary wastewater effluent in a
      continuous enzymatic membrane reactor. Identification of biotransformation
      products.
AB  - In the present study, a novel and efficient technology based on the use of an
      oxidative enzyme was developed to perform the continuous removal of estrogenic
      compounds from polluted wastewaters. A 2 L enzymatic membrane reactor (EMR) was
      successfully operated for 100 h with minimal requirements of laccase for the
      transformation of estrone (E1), 17beta-estradiol (E2), and 17alpha
      ethinylestradiol (EE2)from both buffer solution and real wastewater (filtered
      secondary effluent). When the experiments were performed at high and low
      concentrations of the target compounds, 4 mg/L and 100 MUg/L, not only high
      removal yields (80-100%) but also outstanding reduction of estrogenicity (about
      84-95%) were attained. When the EMR was applied for the treatment of municipal
      wastewaters with real environmental concentrations of the different compounds
      (0.29-1.52 ng/L), excellent results were also achieved indicating the high
      efficiency and potential of the enzymatic reactor system. A second goal of this
      study relied on the identification of the transformation products to elucidate
      the catalytic mechanism of estrogens' transformation by laccase. The formation of
      dimers and trimers of E1, E2, and EE2, as well as the decomposition of E2 into E1
      by laccase-catalyzed treatment, has been demonstrated by liquid chromatography
      atmospheric pressure chemical ionization (LC-APCI) analysis and confirmed by
      determination of accurate masses through liquid chromatography electrospray time
      of-flight mass spectrometry (LC-ESI-TOF). Dimeric products of E2 and EE2 were
      found even when operating at environmental concentrations. Moreover, the reaction
      pathways of laccase-catalyzed transformation of E2 were proposed.

PMID- 23544500
TI  - Complete mitochondrial genome of the Gansu zokor, Eospalax cansus (Rodentia,
      Spalacidae).
AB  - Mysopalacinae (zokors) is a group of fossorial rodents for which the taxonomy has
      yet to reach consensus. Furthermore, due to their fossorial lifestyle, little is
      known about their ecology. Molecular data are important to elucidate such
      aspects. In this paper, the complete mitochondrial DNA genome of Gansu zokor
      (Eospalax cansus) of the type found in Lintan, China was determined. The genome
      is 16,354 bp in length and consists of 13 protein-coding genes, 22 tRNA genes,
      two ribosomal RNA genes, and two main non-coding regions (the control region and
      the origin of the light strand replication), the gene composition and order of
      which are similar to most other mammals. The overall base composition is T 30.0%,
      C 24.2%, A 33.5%, and G 12.3%, with an A + T bias of 63.5%. These mitogenome
      sequence data are potentially important for evolutionary, population genetic, and
      ecological studies of the Mysopalacinae.

PMID- 23544501
TI  - Multiplexed orientation and structure analysis by imaging near-edge X-ray
      absorption fine structure (MOSAIX) for combinatorial surface science.
AB  - Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, as a technique,
      offers detailed information about the bonding environment of molecules at a
      surface. However, because it is a synchrotron based method, beam-time is limited
      and users must typically prioritize and narrowly define the scopes of
      experiments. In this study, we demonstrate a novel method that opens up the
      possibility of the use of large area NEXAFS imaging to pursue combinatorial
      studies. To explore the capabilities of the NIST full field NEXAFS microscope
      available at the National Synchrotron Light Source as a high throughput imaging
      instrument, we collected NEXAFS images from a sample array consisting of 144
      different elements with a periodic sequence of different surface modifications.
      NEXAFS images collected from this model system illustrate how hyperspectral
      NEXAFS data can be used for parallel analysis of large numbers of samples either
      directly from the overall image or by extracting spectra from regions of
      interest. 

PMID- 23544502
TI  - Novel microparticulate systems for the vaginal delivery of nystatin: development
      and characterization.
AB  - To develop more effective antifungal microparticulate therapeutic systems for the
      treatment of Candida vaginitis, microparticles containing nystatin were
      elaborated by emulsification/internal gelation method. Three types of
      microparticles were successfully prepared, alginate microparticles, chitosan and
      poloxamer 407 coated alginate microparticles. DSC and FT-IR studies were
      performed to test the efficacy of the method. After physicochemical
      characterization, mean particle sizes ranged from 36.088 MUm to 56.146 MUm. The
      encapsulation efficiency was found to be similar for alginate and chitosan coated
      microparticles and lower for poloxamer 407 coated. Optimal mucoadhesive
      properties in all kind of microparticles where exhibited. Release studies showed
      the best kinetic parameters for poloxamer 407 coated microparticles. After ex
      vivo permeation studies through porcine vaginal mucosa, and determination of the
      amount of nystatin retained as well as microbiologic studies performed, it could
      be inferred that the developed microparticulate systems offered an antifungal
      effect against Candida albicans without toxic systemic absorption.

PMID- 23544503
TI  - Effect of media components on cell growth and bacterial cellulose production from
      Acetobacter aceti MTCC 2623.
AB  - Acetobacter aceti MTCC 2623 was studied as an alternative microbial source for
      bacterial cellulose (BC) production. Effect of media components on cell growth
      rate, BC production and cellulose characteristics were studied. FTIR results
      showed significant variations in cellulose characteristics produced by A. aceti
      in different media. Results have shown the role of fermentation time on
      crystallinity ratio of BC in different media. Further, effect of six different
      media components on cell growth and BC production was studied using fractional
      factorial design. Citric acid was found to be the most significant media
      component for cell growth rate (95% confidence level, R(2)=0.95). However, direct
      role of these parameters on cellulose production was not established (p
      value>0.05).

PMID- 23544504
TI  - Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal
      microbubble gel.
AB  - In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl
      hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the
      NCHOSC was characterized by FTIR and (1)H NMR. The liposomal microbubble gel
      based on NCHOSC with a high encapsulation efficiency of curcumin was formed and
      improved the solubility of curcumin. The diameter of most liposomal microbubble
      was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room
      temperature and would form a gel at body temperature. Simultaneously, the
      ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The
      results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or
      Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G
      by ultrasound suppressed tumor growth most efficiently. These findings have shed
      some light on the potential NCHOSC material used to liposome-loaded microbubble
      gel for temperature and ultrasound dual-sensitive drug delivery.

PMID- 23544505
TI  - The preparation optimization and immune effect of epimedium polysaccharide
      propolis flavone liposome.
AB  - The preparation conditions of epimedium polysaccharide-propolis flavone liposome
      (EPL) were optimized by response surface methodology taking entrapment rates of
      epimedium polysaccharide and propolis flavone as indexes. The immunoenhancement
      of EPL prepared with optimized condition was determined taking epimedium
      polysaccharide-propolis flavone suspension (EPS) and epimedium polysaccharide
      propolis flavone watery solution (EPW) as control. The results showed that the
      optimized preparation condition was as follows: the ratio of drug to lipid was
      14:1, the ratio of soybean phospholipid to cholesterol was 6:1, and the
      ultrasonic time was 19 min. EPL could significantly promote the proliferation of
      T and B lymphocytes singly or synergistically with PHA or LPS, mRNA expression of
      IL-2 and IL-6 and secretion of IgG and IgM as compared with EPS and EPW. These
      results indicated that liposome could significantly improve the immunoenhancement
      of epimedium polysaccharide-propolis flavone immunopotentiator (EPI) and would be
      as the suitable dosage form of EPI.

PMID- 23544506
TI  - Effect of NaCl on the thermal behaviour of wheat starch in excess and limited
      water.
AB  - The effect of NaCl on the thermal behaviour of wheat starch was investigated with
      particular focus on starch at low moisture contents (25-45 wt%). Increasing the
      level of NaCl reduced the starch peak viscosity (in 90% water) as measured by RVA
      and shifted all of the thermal peaks (up to 120 degrees C) to higher temperatures
      as observed by DSC. Above a moisture content of 45%, the temperature difference
      of the first thermal transition of starch in the presence of 2% NaCl and in the
      absence of NaCl was found to be constant. In the absence of NaCl, the peak
      temperature of gelatinisation (Tp) increased by 12 degrees C (from 62 to 74
      degrees C) as the water content was reduced from 35% to 25%. In the presence of
      2% NaCl, the variation in Tp due to changes in water content was significantly
      reduced. At NaCl concentrations greater than 2% (w/w total), the Tp of the starch
      remained constant irrespective of water content. Evidence of this effect was
      observed in situ using confocal microscopy. In the presence of 2% NaCl, images
      taken at elevated temperatures show little difference in the extent of starch
      swelling at 25% compared to 45% water content. However, in the absence of NaCl,
      significantly more swelling was observed at 45% than at 25% water content. With
      increasing NaCl concentration, the interaction of starch and NaCl became
      dominate. Thus the on-set of the thermal transitions of starch granules is
      primarily controlled by the amount of NaCl present, and secondarily by the water
      content which becomes dominant when the NaCl concentration is low.

PMID- 23544507
TI  - Wheat straw cellulose dissolution and isolation by tetra-n-butylammonium
      hydroxide.
AB  - In this article, a novel and high efficient solvent, tetra-n-Butylammonium
      Hydroxide (TBAH), was used for dissolution and isolation of straw cellulose from
      wheat straw. The composition analysis with gas chromatography (GC) and the
      spectroscopic characterization analysis conducted by X-Ray diffraction
      (XRD)/Fourier transform infrared spectroscopy (FTIR) indicated that straw
      cellulose can be directly dissolved and isolated by TBAH without derivatization.
      The investigation on the properties of straw cellulose isolation was based on the
      results of single factor experiments and orthogonal experiments, with optimum
      conditions for straw cellulose isolation being obtained as follow: reaction
      temperature 60 degrees C, reaction time 40 min, concentration of TBAH 50% and
      ratio of TBAH to straw 10:1 (m/m). In addition, as a solvent for cellulose, TBAH
      could be recycled several times with high activity being retained.

PMID- 23544508
TI  - Fractionation and structural characterization of LiCl-DMSO soluble hemicelluloses
      from tomato.
AB  - To prepare and explore the structure of native hemicellulose from tomato,
      extraction of the natively acetylated polysaccharides was achieved from partially
      depectinated cell walls by DMSO doped with LiCl. DEAE anion exchange
      chromatography of the LiCl-DMSO extract allowed the removal of residual acidic
      pectin and the isolation of acetylated glucuronoxylan. The hemicellulose neutral
      fraction from the anion exchanger was fractionated by size exclusion
      chromatography into xyloglucan (XyG) and galactoglucomannan (GgM) either as
      single major constituents or as mixtures of both. Residual hemicellulose in the
      cell wall was extracted by 4.0 M and not 1.0 M KOH. The fine structure of all
      LiCl-DMSO fractions and alkali extracts was assessed by coupling beta-glucanase,
      beta-mannanase and beta-xylanase enzymatic degradations to the analysis of the
      resulting fragments by HPAEC and MALDI-TOF mass spectrometry. This approach
      revealed substitutions in part of the GgM fractions by pentose residues,
      presumably arabinose and/or xylose occurring in highly substituted block domains.
      It also demonstrated a different glucanase hydrolysis profile from 4.0 M KOH
      compared to LiCl-DMSO soluble fractions. The present extraction and purification
      scheme allow the recovery of several populations of acetylated hemicellulose
      families which emphasize the structural diversity and complexity of these
      polysaccharides.

PMID- 23544509
TI  - Hypolipidemic and antioxidant activities of polysaccharides from Rosae Laevigatae
      Fructus in rats.
AB  - Two major fractions (RLP-1 and RLP-2) were obtained by purifying the crude
      polysaccharides extracted from a traditional Chinese herb Rosae Laevigatae
      Fructus. The average molecular weight of RLP-1 and RLP-2 was 21.5 kDa and 16.1
      kDa, respectively. Monosaccharide analysis indicated that RLP-1 was composed of
      xylose, mannose and galactose in the molar ratio of 1:11:8, while RLP-2 was only
      a glucan. Oral administration of RLP-1 could significantly decrease levels of
      serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein
      cholesterol (LDL-C), inhibit hepatic lipid accumulation, increase antioxidant
      lipids and up-regulate expressions of peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) and lipoprotein lipase (LPL) in hyperlipidemia rats. These
      results suggest that RLP-1 improve hyperlipidemia possibly through regulating
      PPAR-mediated lipid metabolism. Therefore, could be explored as a possible agent
      for hyperlipidemia.

PMID- 23544510
TI  - The composites based on plasticized starch and graphene oxide/reduced graphene
      oxide.
AB  - The graphite was oxidized to prepare graphene oxide (GO), and GO was reduced by
      glucose to obtain reduced graphene oxide (RGO) sheet. There were abundant and
      residual oxygen-containing groups on GO and RGO, respectively. Compared to
      graphite, the GO and RGO sheets appeared flat and transparent, and the aqueous
      suspensions followed the Lambert-Beer's law well. The composites were also
      fabricated by using GO and RGO as the filler in plasticized-starch (PS) matrix.
      Because of more oxygen-containing groups, GO could form the stronger interaction
      with PS matrix than RGO. And GO/PS composites exhibited better tensile strength,
      elongation at break and moisture barrier than RGO/PS composites, but lower
      thermal stability. GO/PS composites could protect against UV light, while the
      conductivities of RGO/PS composites could reach 1.07*10(-4), 6.92*10(-4) and 0.01
      S/cm, respectively stored at RH50, 75 and 100%.

PMID- 23544511
TI  - Isolation of cellulose from rice straw and its conversion into cellulose acetate
      catalyzed by phosphotungstic acid.
AB  - Cellulose was isolated from rice straw by pretreatment with dilute alkaline and
      acid solutions successively, and it was further transferred into cellulose
      acetate in the presence of acetic anhydride and phosphotungstic acid
      (H3PW12O40.6H2O). The removal of hemicellulose and lignin was affected by the
      concentration of KOH and the immersion time in acetic acid solution, and 83wt.%
      content of cellulose in the treated rice straw was obtained after pretreatment
      with 4% KOH and immersion in acetic acid for 5h. Phosphotungstic acid was found
      to be an effective catalyst for the acetylation of the cellulose derived from
      rice straw. The degree of substitution (DS) values revealed a significant effect
      for the solubility of cellulose acetate, and the acetone-soluble cellulose
      acetate with DS values around 2.2 can be obtained by changing the amount of
      phosphotungstic acid and the time of acetylation. Both the structure of cellulose
      separated from rice straw and cellulose acetate were confirmed by FTIR and XRD.

PMID- 23544512
TI  - Synthesis and characterization of Eu(III) complexes of modified cellulose and
      poly(N-isopropylacrylamide).
AB  - A series of thermo-responsive copolymers of poly(N-isopropylacrylamide) (PNIPAM)
      and cellulose were synthesized via atom transfer radical polymerization (ATRP)
      using N-isopropylacrylamide as the monomer, cellulose acetate as the initiator,
      and CuCl/tris(2-dimethylaminoethyl)amine (Me6TREN) as a catalytic system. The
      resulting polymers had a narrow range of polydispersity indexes 1.27-1.37, and
      molecular weights of 8600-17,300 g mol(-1). Novel functional complexes of
      cellulose-g-PNIPAM/Eu(III) with excellent thermosensitive and fluorescent
      properties were then formed by the chelation of copolymers and europium(III)
      ions. The maximum emission intensity of the complexes at 613 nm was enhanced by a
      factor of approximately 10 relative to that of the corresponding Eu(III)
      complexes. Additionally, the lower critical solution temperatures (LCSTs) of
      cellulose-g-PNIPAM/Eu(III) were slightly greater than those of the copolymers.

PMID- 23544513
TI  - Diffusion of ions in a calcium alginate hydrogel-structure is the primary factor
      controlling diffusion.
AB  - The diffusion of solutes has been evaluated in an alginate hydrogel as a function
      of its structure. The role of solute and gel charge on the diffusion measurements
      were of particular interest. Diffusion coefficients were measured using
      fluorescence correlation spectroscopy as a function of solute charge and size,
      bulk solution ionic strength and pH, and gel density. Diffusion coefficients of
      fluorescent dextrans with hydrodynamic radii up to 6 nm were reduced by 30% in a
      1.8% (w/w) hydrogel whereas they were reduced by only 2% in a 0.2% (w/w)
      hydrogel. The role of ionic strength was examined for various concentrations (0.1
      100 mM) and compositions of ions (Na(+), Ca(2+) or mixtures thereof). The
      diffusion coefficient of a small charged probe (rhodamine 6G, R6G(+)) did not
      change significantly with increasing ionic strength when sodium was used as the
      counter ion. The diffusion coefficient was only moderately influenced by the
      charge of solutes (from +1 to -2). Similarly, pH variations from 3 to 9 had
      little impact on the diffusion coefficients of R6G(+) in the gel. On the other
      hand, the addition of Ca(2+) had a significant impact on gel compactness, which
      led to a significant reduction in solute diffusion. For the calcium alginate
      hydrogels, structural modifications resulting from Ca binding were much more
      important than electrostatic effects due to modifications of the gel Donnan
      potential.

PMID- 23544514
TI  - Preparation of peach gum polysaccharides using hydrogen peroxide.
AB  - Most polysaccharides cannot dissolve in water but can be hydrolysed using
      hydrogen peroxide (H2O2) to yield a water-soluble product. This study presents a
      method of preparing water-soluble polysaccharides from peach gum by hydrolysis
      using H2O2. Extraction was monitored by the recovery rate. Factors affecting the
      hydrolysis of peach gum were investigated, and the optimum hydrolysis conditions
      were determined as follows: time, 8 h; temperature, 55 degrees C; H2O2
      concentration, 4% (v/v); and NaOH concentration, 2.0 M. The hydrolysates were
      filtered, neutralised with HCl, concentrated to ~20% (w/v), precipitated with 5
      volumes of ethanol, freeze-dried, and ground to yield a water soluble and white
      powder. The polysaccharide content of the product was 97.8%, and the yield was
      83.6% (w/w).

PMID- 23544515
TI  - Agaricus bisporus and Agaricus brasiliensis (1->6)-beta-D-glucans show
      immunostimulatory activity on human THP-1 derived macrophages.
AB  - The (1->6)-beta-D-glucans from Agaricus bisporus and Agaricus brasiliensis were
      purified to evaluate their effects on the innate immune system. THP-1 macrophages
      were used to investigate the induction of the expression of TNF-alpha, IL1beta,
      and COX-2 by RT-PCR. The purification of the polysaccharides gave rise to
      fractions containing 96-98% of glucose. The samples were analyzed by GC-MS, HPSEC
      and (13)C NMR, which confirmed the presence of homogeneous (1->6)-beta-D-glucans.
      The beta-glucans were incubated with THP-1 derived macrophages, for 3 h and 6 h
      to evaluate their effects on the expression of pro-inflammatory genes. Both beta
      glucans stimulated the expression of such genes as much as the pro-inflammatory
      control (LPS). When the cells were incubated with LPS+beta-glucan, a significant
      inhibition of the expression of IL-1beta and COX-2 was observed for both
      treatments after 3 h of incubation. By the results, we conclude that the (1->6)
      beta-D-glucans present an immunostimulatory activity when administered to THP-1
      derived macrophages.

PMID- 23544516
TI  - Oral administration of heparin or heparosan increases the Lactobacillus
      population in gut microbiota of rats.
AB  - Heparin and heparosan have been confirmed to be effective blockers in inhibiting
      adhesion of pathogens in vitro. However, their effects on gut microbiota in vivo
      remain unknown. Here we have studied the effects of oral administration of
      heparin or heparosan on gut microbiota in rats by polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE). Results showed that the
      predominant bacterial communities in the feces of heparin- or heparosan-treated
      animals were different from those of the saline-treated animals, with increased
      Lactobacillus spp. and decreased Enterococcus sp. Different DGGE banding patterns
      were also observed for the subpopulations of Lactobacillus and Bacteroides
      groups. In conclusion, heparin or heparosan may be used as an effective gut
      microbiota modulator by increasing the subpopulation of Lactobacillus.

PMID- 23544517
TI  - Composite polyelectrolyte multilayer membranes for oligosaccharides
      nanofiltration separation.
AB  - In the present work, composite polyelectrolyte multilayer (C-PEM) membranes were
      fabricated by using layer-by-layer (LbL) assembly technique for oligosaccharides
      nanofiltration (NF) separation. Specifically, the (chitosan/poly(styrene
      sulfonate) (PSS))3 multilayers designated as the middle layer (ML) were first
      deposited on the hydrolyzed polyacrylonitrile (PAN) ultrafiltration membranes,
      which were designated as the support layer. Then, the (poly(allylamine
      hydrochloride) (PAH)/PSS)2 multilayers designated as the top layer (TL) were
      deposited on the ML to form C-PEM membranes. When utilized for oligosaccharides
      NF separation, C-PEM membranes exhibited desirable performance compared to single
      paired PEM membranes such as (PAH/PSS)5 and (chitosan/PSS)5 membranes owing to
      the collaboration of the TL and ML. In detail, C-PEM membranes acquired a
      permeation flux of 3.7+/-0.3 L m(-2) h(-1), 100% rejection of oligosaccharides
      and 63.0+/-0.5% rejection of glucose along with a high maltose/glucose
      selectivity of 46, demonstrating the promising potential for one-step membrane
      separation of oligosaccharides mixture.

PMID- 23544518
TI  - Extraction optimization of Angelica sinensis polysaccharides and its antioxidant
      activity in vivo.
AB  - Extraction of Angelica sinensis polysaccharides (ASP) was optimized by the
      utilization of response surface methodology, RSM. Through the analysis,
      extraction time and water/solid were found to be the most significant factors.
      Based on contour plots and variance analysis, optimum operational conditions for
      maximizing polysaccharides yield (5.6%) were found to be extraction time 130 min,
      water/solid 5, and extraction number 5. A. sinensis polysaccharides (150 and 300
      mg/kg) were administered for 15 days. The hepatoprotective activity was assessed
      using various biochemical parameters. Serum aspartate aminotransferase (AST),
      alanine aminotransfere (ALT) and alkaline phosphatase (ALP) levels were
      significantly restored toward normalization by the extracts (150 and 300 mg/kg
      body weight). ASP (150 and 300 mg/kg body weight) significantly increased the
      levels of antioxidant enzymes. It can be concluded that ASP possesses significant
      protective effect against hepatotoxicity induced by carbon tetrachloride (CCl4).
      This protective effect appears due to ASP antioxidant properties.

PMID- 23544519
TI  - Microwave-assisted synthesis of alkyl cellulose in aqueous medium.
AB  - Alkyl celluloses are commercial products that are made typically in an alcohol
      medium over the course of several hours. In this work an alternative, simplified
      synthesis of alkyl cellulose is reported, using microwave irradiation and aqueous
      alkaline medium. No alcohol is needed during the reaction. Reaction time is less
      than 30 min. Conversion varies from 54 to 87%. The degree of substitution varied
      from 0.2 to 1.0. The production of methyl cellulose and ethyl cellulose was
      confirmed by (13)C NMR and FTIR analysis.

PMID- 23544520
TI  - Aspects of determining the molecular weight of cyclodextrin polymers and
      oligomers by static light scattering.
AB  - Methodic issues affecting the use of static light scattering to determine the
      average molecular weight of cyclodextrin poly- and oligomers are discussed. The
      critical features which enable accurate measurement such as aggregation behavior
      and segment-segment interaction are elucidated. Static light scattering data
      supported with globule size and aggregate state analysis (as determined by
      dynamic light scattering) allowed the aggregate-free state of the samples to be
      justified and the ideal globular conformation of the macromolecules to be
      corroborated. These molecular characteristics were demonstrated for uncharged,
      charged and fluorescent randomly crosslinked water soluble cyclodextrin poly- and
      oligomers.

PMID- 23544521
TI  - Lactarius rufus (1->3),(1->6)-beta-D-glucans: structure, antinociceptive and anti
      inflammatory effects.
AB  - Medicinal health benefits uses of edible as well as non-edible mushrooms have
      been long recognized. The pharmacological potential of mushrooms, especially
      antitumor, immunostimulatory and anti-inflammatory activities has been
      documented. Wild ectomycorrhizal mushroom, Lactarius rufus had the anti
      inflammatory and antinociceptive potential of their polysaccharides evaluated
      using the formalin model. Two structurally different (1->3),(1->6)-linked beta-D
      glucans were isolated from fruiting bodies. Soluble (FSHW) beta-D-glucan 1-30 mg
      kg(-1) produced potent inhibition of inflammatory pain caused by formalin when
      compared with the insoluble one (IHW), suggesting that solubility and/or
      branching degree could alter the activity of beta-glucans. Their structures were
      determined using mono- and bi-dimensional NMR spectroscopy, methylation analysis,
      and controlled Smith degradation. They were beta-D-glucans, with a main chain of
      (1->3)-linked Glcp residues, substituted at O-6 by single-unit Glcp side chains
      (IHW), on average to every fourth residue of the backbone, or by mono- and few
      oligosaccharide side chains for soluble beta-glucan.

PMID- 23544522
TI  - The effect of poly-L-lysine structure on the pH response of polygalacturonic acid
      based multilayers.
AB  - The effect of poly-L-lysine (PLL) molecular weight and structure on pH stability
      of polygalacturonic acid (PGaLA)-based multilayer films is studied over a pH
      cycle 7.0-1.6-7.0. The multilayer assembled with the lowest molecular weight PLL
      (1 kDa) showed the largest pH response. Only 12% of the mass remained and a
      preferential loss of PLL was observed. Extensive structural reorganisation of the
      layer as the pH was increased was due to the PGaLA reionisation leading to
      extensive net loss of hydrated mass. The multilayers assembled with the higher
      molecular weight linear PLLs (10 kDa, 200 kDa) showed loss of about 50% of their
      initial polymer mass. The multilayer assembled with the dendrimer (22 kDa) showed
      a stronger response to pH compared to the linear higher molecular weight PLLs.
      Over the pH cycle a loss of about 60% polymer mass and a decrease in the film
      thickness was observed. Despite having a reduced density at pH 1.6, the density
      substantially recovered to 0.54 g mL(-1) on return to pH 7.0.

PMID- 23544523
TI  - Electrospun curcumin-loaded fibers with potential biomedical applications.
AB  - Polyvinyl alcohol (PVA) nanofibers loaded with curcumin or its beta-cyclodextrin
      (CD) inclusion complex were successfully prepared using an electrospinning
      process. The influence of curcumin or CD-curcumin complex content on fiber
      formation and quality was investigated. X-ray diffraction and differential
      scanning calorimetry analyses of the fibers, together with electron microscope
      evidence, demonstrated that curcumin is likely to be present as crystalline
      aggregates in the fibers, while its CD complex is more evenly distributed. (1)H
      NMR analysis indicated that the chemical structure of curcumin was preserved
      during the electrospinning process. Thermogravimetric analysis demonstrated that
      inclusion into nanofibers enhanced the thermal stability of curcumin. In vitro
      dissolution tests showed that the drug release profiles of the PVA/curcumin and
      PVA/complex fibers were different, with release from the latter occurring more
      rapidly. Release from both fiber types was found to be largely governed by a
      diffusion-controlled mechanism; two sequential stages for drug release were
      observed.

PMID- 23544524
TI  - Production of nanocrystalline cellulose from lignocellulosic biomass: technology
      and applications.
AB  - The use of renewables materials for industrial applications is becoming impellent
      due to the increasing demand of alternatives to scarce and unrenewable petroleum
      supplies. In this regard, nanocrystalline cellulose, NCC, derived from cellulose,
      the most abundant biopolymer, is one of the most promising materials. NCC has
      unique features, interesting for the development of new materials: the abundance
      of the source cellulose, its renewability and environmentally benign nature, its
      mechanical properties and its nano-scaled dimensions open a wide range of
      possible properties to be discovered. One of the most promising uses of NCC is in
      polymer matrix nanocomposites, because it can provide a significant
      reinforcement. This review provides an overview on this emerging nanomaterial,
      focusing on extraction procedures, especially from lignocellulosic biomass, and
      on technological developments and applications of NCC-based materials. Challenges
      and future opportunities of NCC-based materials will be are discussed as well as
      obstacles remaining for their large use.

PMID- 23544525
TI  - Ice-templated hydrogels based on chitosan with tailored porous morphology.
AB  - Preparation and morphological characterization of some novel hydrogels based on
      chitosan (CS) with porous structure tailored by ice-templating and porogen
      leaching are presented in the paper. Poly(methylmethacrylate) (PMMA), as
      fractionated particles, has been used as polymer porogen. The influence of the
      mesh of the fractionated PMMA particles, the weight ratio between CS and
      fractionated PMMA particles, and the speed of the crystallization, on the
      internal morphology of the hydrogels have been deeply investigated. The
      morphology of the obtained hydrogels was observed by scanning electron microscopy
      (SEM). As a function of the synthesis conditions, hydrogels with a heterogeneous
      morphology consisting of randomly and evenly distributed polyhedral pores, or
      with an oriented structure, which has microchanneled structures arranged along
      the freezing direction, were generated.

PMID- 23544526
TI  - Structure and antiviral activity of arabinogalactan with (1->6)-beta-D-galactan
      core from Stevia rebaudiana leaves.
AB  - Cell wall polysaccharides from leaves of Stevia rebaudiana were extracted
      successively with water and with aq. 10% KOH. After the purification steps,
      homogeneous fractions (SFW-10RM and SSFK-10RM) were analyzed by sugar
      composition, HPSEC, methylation and (13)C NMR spectroscopy analysis. The results
      showed that SFW-10RM is a pectic arabinogalactan with an unusual beta-(1->6)
      linked D-Galp residues forming the main chain. Approximately 38% of the beta-D
      Galp units of the backbone carry branches on position O-3, consisting of single D
      Galp units or arabinan side chains. Arabinose residues were found to occupy
      mostly the terminal positions in both furanose and pyranose forms and as 2-, 5-
      and 3,5-linked residues in these side chains. Fraction SSFK-10RM is a similar
      arabinogalactan, differing mainly in the relative proportions of arabinans
      attached to the galactan core and in the content of D-GalpA residues present in
      the pectic domain. The crude aqueous and alkaline extracts and homogeneous SSFK
      10RM showed antiviral activity against Herpes Simplex Virus type-1 (HSV-1) in
      vitro.

PMID- 23544527
TI  - Efficient gene transfection in the neurotypic cells by star-shaped polymer
      consisting of beta-cyclodextrin core and poly(amidoamine) dendron arms.
AB  - In order to develop the effective vectors that had high gene transfection
      capability and low cytotoxicity in the neuronal cells, we tested the star-shaped
      polymer consisting of beta-cyclodextrin core and poly(amidoamine) (PAMAM) dendron
      arms [beta-CD-(D3)7] as the vector to transfect the human neuroblastoma SH-SY5Y
      cells. The physicochemical properties of the beta-CD-(D3)7/plasmid DNA (pDNA)
      complexes were characterized by using gel electrophoresis, dynamic light
      scattering, transmission electron microscopy and zeta-potential experiments.
      Among the human neuroblastoma SH-SY5Y cells, beta-CD-(D3)7/pDNA complex
      demonstrated a lower toxicity compared to those of PAMAM (G=4, with an
      ethylenediamine core)/pDNA complex. When the N/P ratio was over 20, it was
      observed that PAMAM had a faster increment in toxicity compared to beta-CD-(D3)7.
      Fluorescent image, confocal microscopy image and flow cytometry showed that beta
      CD-(D3)7/pDNA complexes had significantly higher transgene activity than that of
      PAMAM/pDNA complexes. For example, the transfection efficiency was 20% and 7.5%
      for beta-CD-(D3)7/pDNA and PAMAM/pDNA complexes, respectively. These results
      indicated that beta-CD-(D3)7 might be a promising candidate for neurotypic cells
      gene delivery with the characteristics of good biocompatibility, relatively high
      gene transfection capability and potential in vivo gene delivery ability.

PMID- 23544528
TI  - Effect of preparation method on the properties of potato starch acetates with an
      equal degree of substitution.
AB  - Acetylated retrograded starch is one of the forms of resistant starch (RS3/4).
      Apart from the known resistance to amylolysis, it is characterized by the
      capability to form viscous pastes. Properties of this type of acetates are mainly
      determined by the degree of substitution and raw material used for
      esterification. The objective of this study was to produce starch acetates with a
      degree of substitution DS=0.1 from native potato starch and retrograded potato
      starch, and to compare selected properties of the resultant preparations.
      Retrograded starch was produced by freezing pastes with concentrations of 1, 4,
      10, 18 or 30 g/100 g. Starch acetates with a degree of substitution DS~0.1 were
      produced from native or retrograded starch through acetylation with various doses
      of acetic acid anhydride (6.5-26.0 cm(3)/100 g of starch). The preparations
      produced were characterized by various properties. A positive correlation was
      observed between resistance to amylolysis and the number of acetyl groups at C2
      and C3 the produced starch acetates.

PMID- 23544529
TI  - Physical-mechanical and antimicrobial properties of nanocomposite films with
      pediocin and ZnO nanoparticles.
AB  - This work aimed to develop nanocomposite films of methyl cellulose (MC)
      incorporated with pediocin and zinc oxide nanoparticles (nanoZnO) using the
      central composite design and response surface methodology. This study evaluated
      film physical-mechanical properties, including crystallography by X-ray
      diffraction, mechanical resistance, swelling and color properties, microscopy
      characterization, thermal stability, as well as antimicrobial activity against
      Staphylococcus aureus and Listeria monocytogenes. NanoZnO and pediocin affected
      the crystallinity of MC. Load at break and tensile strength at break did not
      differ among films. NanoZnO and pediocin significantly affected the elongation at
      break. Pediocin produced yellowish films, but nano ZnO balanced this effect,
      resulting in a whitish coloration. Nano ZnO exhibited good intercalation in MC
      and the addition of pediocin in high concentrations resulted crater-like pits in
      the film surfaces. Swelling of films diminished significantly compared to
      control. Higher concentrations of Nano ZnO resulted in enhanced thermal
      stability. Nanocomposite films presented antimicrobial activity against tested
      microorganisms.

PMID- 23544531
TI  - Simultaneous analysis of 18 mineral elements in Cyclocarya paliurus
      polysaccharide by ICP-AES.
AB  - The contents of 18 kinds of mineral elements in Cyclocarya paliurus
      polysaccharide samples were determined by ICP-AES. The limits of detection (LOD)
      of the method for 18 elements were in the range of 0.01-3.80 mg/kg. The average
      recoveries obtained by the standard addition method were found between 94.34% and
      105.69% (RSD, 1.01-4.23%). The results showed that C. paliurus polysaccharides
      were abundant in major and trace elements which are healthy for human body. The
      contents of Ca, Al, Mg, K, Fe, Mn and P were very high, ranging from 274.5+/-10.3
      to 5980.0+/-102.7 mg/kg, while the contents of Zn, Na, Se, Cr, Pb, Cu and As
      ranged from 0.9+/-0.1 to 37.1+/-4.2 mg/kg. Finally, the levels of Ni, Cd, V and
      Co were not detected in the samples. ICP-AES is a simple, precise and efficient
      method for the determination of many mineral elements in polysaccharide samples
      simultaneously.

PMID- 23544530
TI  - Organized polysaccharide fibers as stable drug carriers.
AB  - Many challenges arise during the development of new drug carrier systems, and
      paramount among them are safety, solubility and controlled release requirements.
      Although synthetic polymers are effective, the possibility of side effects
      imposes restrictions on their acceptable use and dose limits. Thus, a new drug
      carrier system that is safe to handle and free from side effects is very much in
      need and food grade polysaccharides stand tall as worthy alternatives. Herein, we
      demonstrate for the first time the feasibility of sodium iota-carrageenan fibers
      and their distinctive water pockets to embed and release a wide variety of drug
      molecules. Structural analysis has revealed the existence of crystalline network
      in the fibers even after encapsulating the drug molecules, and iota-carrageenan
      maintains its characteristic and reproducible double helical structure suggesting
      that the composites thus produced are reminiscent of cocrystals. The melting
      properties of iota-carrageenan:drug complexes are distinctly different from those
      of either drug or iota-carrageenan fiber. The encapsulated drugs are released in
      a sustained manner from the fiber matrix. Overall, our research provides an
      elegant opportunity for developing effective drug carriers with stable network
      toward enhancing and/or controlling bioavailability and extending shelf-life of
      drug molecules using GRAS excipients, food polysaccharides, that are inexpensive
      and non-toxic.

PMID- 23544532
TI  - Synthesis, physiochemical and optical properties of chitosan based dye containing
      naphthalimide group.
AB  - A new biopolymer dye containing naphthalimide moiety was synthesized by reaction
      of N-naphthaloyl chitosan with 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazino-3
      quinolinecarboxylic acid. N-naphthaloyl chitosan was synthesized by reaction of
      chitosan with 4-bromo-1,8-naphthalic anhydride in aqueous media by greener
      approach. The degree of substitution of chitosan biopolymer dye is 0.55 with a
      yield of 70%. The synthesized materials were characterized by using UV-vis, (1)H
      NMR, FTIR, and FT-Raman spectroscopy. Some physical properties and surface
      morphology were characterized by X-ray diffraction (XRD), thermogravimetric
      analysis (TGA), differential scanning calorimetry (DSC) and scanning electron
      microscopy (SEM). Optical properties of chitosan biopolymer dye were evaluated by
      photoluminescence (PL) spectroscopy that showed red shift (lambda(em)) peak at
      442 nm and 551 nm at excitation wavelength 325 nm in comparison to chitosan. The
      solubility of chitosan biopolymer dye increased in most of the organic solvents.
      These results may provide new perspectives in biomedical applications as an
      optical and sensitive biosensor material.

PMID- 23544533
TI  - Green synthesis of polysaccharide/gold nanoparticle nanocomposite: an efficient
      ammonia sensor.
AB  - A low cost eco-friendly method for the synthesis of gold nanoparticles (AuNPs)
      using guar gum (GG) as a reducing agent is reported. The nanoparticles obtained
      are characterized by UV-vis spectroscopy, scanning electron microscopy (SEM),
      transmission electron microscopy (TEM) and X-ray diffraction (XRD). Based on
      these results, a potential mechanism for this method of AuNPs synthesis is
      discussed. GG/AuNPs nanocomposite (GG/AuNPs NC) was exploited for optical sensor
      for detection of aqueous ammonia based on surface plasmon resonance (SPR). It was
      found to have good reproducibility, response times of ~10 s and excellent
      sensitivity with a detection limit of 1ppb (parts-per-billion). This system
      allows the rapid production of an ultra-low-cost GG/AuNPs NC-based aqueous
      ammonia sensor.

PMID- 23544534
TI  - Effect of castor oil enrichment layer produced by reaction on the properties of
      PLA/HDI-g-starch blends.
AB  - Blends of entirely bio-sourced polymers, namely polylactide (PLA) and starch,
      have been melt-compounded by lab-scale co-extruder with castor oil (CO) as a
      plasticizer. The enrichment of castor oil on starch had great effect on the
      properties of the blends. If the castor oil was mainly dispersed in PLA matrix,
      the properties of the blends were poor, but when the hexamethylenediisocyanate
      (HDI) was grafted on starch granules the ready reactions between the hydroxyl on
      CO and the isocyante on the HDI-grafted starch (HGSTs) brought CO molecules
      enriched on starch particles. DSC analysis shows that the CO layer on starch has
      a positive effect on the crystallization of PLA in the ternary blend. The
      accumulation of CO on starch greatly improves the toughness and impact strength
      of PLA/starch blends. The grafting content of HDI on the starch granules
      primarily determined the compatibility and properties of the resulted blends.

PMID- 23544535
TI  - Mucoadhesive 4-carboxybenzenesulfonamide-chitosan with antibacterial properties.
AB  - The mucoadhesive property of chitosan, especially in an acidic (<pH 6.0)
      environment, was increased by conjugating an aromatic sulfonamide group at the C2
      N position of chitosan. Four different feeding ratios of 4
      carboxybenzensulfonamide (4-CBS) to chitosan in the presence of 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide hydrochloride as a coupling agent were
      investigated. The 0.2:1 (w/w) ratio 4-CBS:chitosan revealed a 20-fold stronger
      mucoadhesion to mucin type II than the native chitosan in the simulated gastric
      fluid (SGF; pH 1.2), and a swelling ratio after 1 h in water, SGF and simulated
      intestinal fluid (pH 7.4) of about 2.9-, 3.0- and 3.4-fold higher than that of
      chitosan, respectively. In tissue culture, the 4-CBS-chitosan, like chitosan,
      were found to be non-cytotoxic to the Vero, KB, MCF-7 and NCI-H187 cell lines but
      showed potential antibacterial activity against Escherichia coli and
      Staphlyococcus aureus as model gram-negative and gram-positive bacteria,
      respectively.

PMID- 23544536
TI  - Structure of a novel exopolysaccharide produced by Burkholderia vietnamiensis, a
      cystic fibrosis opportunistic pathogen.
AB  - Burkholderia vietnamiensis belongs to the Burkholderia cepacia complex and is an
      opportunistic pathogen for cystic fibrosis patients. As many other Burkholderia
      species, it has a mucoide phenotype, producing abundant exopolysaccharide. In
      general, polysaccharides contribute to bacterial survival in a hostile
      environment, are recognised as virulence factors and as important components in
      biofilm formation. The primary structure of the exopolysaccharide produced by B.
      vietnamiensis LMG 10929 was determined mainly by use of 1D and 2D NMR
      spectroscopy and ESI mass spectrometry. The polymer consists of the
      trisaccharidic backbone 3)-beta-D-Glcp-(1->4)-alpha-D-Glcp-(1->3)-alpha-L-Fucp-(1
      > with the side chain alpha-D-Glcp-(1->4)-alpha-D-GlcAp-(1->3)-alpha-L-Fucp-(1->
      linked to C-3 of the alpha-D-Glcp residue. The polysaccharide also bears acetyl
      substituents on about 20% of its repeating units and on at least two different
      positions. The presence of fucose residues is a novel structural feature among
      the exopolysaccharides produced by species of the B. cepacia complex.

PMID- 23544537
TI  - Homogeneous synthesis of chitin-based acrylate superabsorbents in NaOH/urea
      solution.
AB  - A modified freezing-thawing cyclic (FTC) process was applied to dissolve the
      chitin in NaOH/urea solution. A transparent homogeneous solution was obtained. It
      was utilized directly for preparing the superabsorbent polymers (SAPs) by
      grafting copolymerization under static solution conditions without nitrogen
      protection. The acrylic acid was used conveniently without prior neutralization.
      The final products existed as hydrogels without excess reagent emissions. The
      adsorption capacity and yield of SAP that was prepared in the optimum conditions
      was 2833 g/g and 81.65%, respectively, higher than one-time FTC program prepared
      with 2527 g/g and 15.44%. Furthermore, it formed a uniform and transparent gel
      without any residual chitin particles. The regenerated chitin and SAPs were
      characterized by SEM, FTIR, XRD, and TG. The samples prepared by the new method
      presented a more amorphous state with good thermal stability, suggesting that
      this convenient preparation method for a potential industrial application's
      pathway.

PMID- 23544538
TI  - Chitosan and oligochitosan enhance the resistance of peach fruit to brown rot.
AB  - The effects of chitosan and oligachitosan on resistance induction of peach fruit
      against brown rot caused by Monilinia fructicola were investigated. Both chitosan
      and oligochitosan showed significant effect on controlling this disease.
      Moreover, chitosan and oligochitosan delayed fruit softening and senescence. The
      two antifungal substances enhanced antioxidant and defense-related enzymes, such
      as catalase (CAT), peroxidase (POD), beta-1,3-glucanase (GLU) and chitinase
      (CHI), and they also stimulated the transcript expression of POD and GLU. These
      findings suggest that the effects of chitosan and oligochitosan on disease
      control and quality maintenance of peach fruit may be associated with their
      antioxidant property and the elicitation of defense responses in fruit.

PMID- 23544539
TI  - Preparation of entangled nanocellulose fibers from APMP and its magnetic
      functional property as matrix.
AB  - Nanocellulose fibers (NCFs) aerogels were prepared from poplar alkaline peroxide
      mechanical pulp (APMP) using physical ultrasonication method. As raw materials,
      the unique mechanical effects of APMP cause the fiber folding and loose during
      the pulping process, which was beneficial to further chemical purification and
      subsequent treatment for long and entangled NCFs. The obtained NCFs exhibited
      higher crystallinity (77.8%) compared with that of APMP (72.6%) together with
      diameters range from 20 to 90 nm and self-assembled to network. The primary
      thermal degradation of NCFs occurred at 331.5 degrees C. The prepared NCFs
      network aerogels acted as matrix which can prevent the growth and aggregation of
      ferromagnetic CoFe2O4 nanoparticles. The ratio of the CoFe2O4 of magnetic
      composites increased from 34 wt% to 75 wt%, and the magnetic properties were all
      increased with increasing the reaction concentration of FeSO4/CoCl2 salt.

PMID- 23544540
TI  - Evaluation of tropicamide-loaded tamarind seed xyloglucan nanoaggregates for
      ophthalmic delivery.
AB  - The present study was aimed to prepare tamarind seed nanoaggregates and its
      evaluation for ophthalmic delivery. The preparation of tropicamide-loaded
      tamarind seed xyloglucan nanoaggregates was optimized using face centred central
      composite experimental design, employing the concentrations of tamarind seed
      xyloglucan and Poloxamer-407, as independent variables. The results revealed that
      concentration of TSX has a significant antagonistic effect on particle size,
      while poloxamer displayed a significant synergistic effect on encapsulation
      efficiency. The optimal concentrations of TSX and poloxamer were found to be
      0.45% (w/v) and 0.5% (w/v) respectively. The optimized formulation of tropicamide
      loaded TSX nanoaggregates showed a significantly higher corneal permeation of
      tropicamide across the isolated goat cornea compared to commercial conventional
      aqueous formulation. The results revealed excellent mucoadhesive properties of
      TSX nanoaggregates. Further, the tropicamide-loaded TSX nanoaggregates
      formulation showed excellent ocular tolerance and biocompatibility as determined
      by hen's egg test chorioallantoic membrane and resazurin assay on Vero cell
      lines.

PMID- 23544541
TI  - Supramolecular complexes of maltodextrin and furosemide polymorphs: a new
      approach for delivery systems.
AB  - We present new supramolecular complexes of two different solid forms of
      furosemide (I or II) with maltodextrin, in order to explore their application as
      delivery systems improving the bioavailability of the drug. The complexation in
      solution was evaluated by (1)H nuclear magnetic resonance experiments and phase
      solubility studies. The products in solid state were exhaustively characterized
      by using spectroscopic techniques ((13)C solid state nuclear magnetic resonance,
      infrared, scanning electron microscopy, X-ray powder diffractometry) and thermal
      analysis. (1)H relaxation times experiments gave further support in
      distinguishing the new solid forms. Dissolution studies in simulated gastric
      fluid showed that both supramolecular complexes presented significant increase in
      the dissolution, while the corresponding physical mixtures exhibited the most
      discriminating conditions between the furosemide forms I and II. Our results
      suggest the enhancement of the solubility and the dissolution of furosemide in
      the new complexes, making them promising candidates for the preparation of
      alternative matrices in oral pharmaceutical formulations.

PMID- 23544542
TI  - Stimulation of lymphocyte proliferation by oyster glycogen sulfated at C-6
      position.
AB  - In this study, glycogen was extracted from oyster Ostrea talienwhanensis Crosse
      and used as a model to investigate the structure-activity correlation of
      polysaccharides. Purified oyster glycogen was characterized by methylation
      analysis, nuclear magnetic resonance (NMR) spectroscopy and infrared spectroscopy
      (IR). The oyster glycogen was subsequently sulfated by chlorosulfonic acid
      pyridine method, and a C-6 substituted species (SOG) was identified to be the
      primary sulfated oyster glycogen species by (13)C NMR spectroscopy. The molecular
      weight and sulfate content of the SOG was determined to be 3.2*10(4) g/mol and
      33.6%, respectively. Another sulfated oyster glycogen species (SOG1) with C-2 and
      C-3 substitution was also identified at a lesser amount in the final product. SOG
      exhibited a much stronger stimulation effect to splenic lymphocyte proliferation
      than SOG1 in vitro, indicating that the position of sulfate substitution is a
      major determining factor on the efficacy of sulfated glycogens to stimulate
      lymphocyte proliferation.

PMID- 23544543
TI  - Self-assembled nanoparticles based on amphiphilic chitosan derivative and
      hyaluronic acid for gene delivery.
AB  - The present work described nanoparticles (NPs) made of oleoyl-carboxymethy
      chitosan (OCMCS)/hyaluronic acid (HA) using coacervation process as novel
      potential carriers for gene delivery. An N/P ratio of 5 and OCMCS/HA weight ratio
      of 4 were the optimal conditions leading to the smallest (164.94 nm), positive
      charged (+14.2 mV) and monodispersed NPs. OCMCS-HA/DNA (OHD) NPs showed higher in
      vitro DNA release rates and increased cellular uptake by Caco-2 cells due to the
      HA involved in NPs. The MTT survival assay indicated no significant cytotoxicity.
      The transfection efficiency of OHD NPs was 5-fold higher than OCMCS/DNA (OD) NPs;
      however, it decreased significantly in the presence of excess free HA. The
      results indicated that OHD NPs internalized in Caco-2 cells were mediated by the
      hyaluronan receptor CD44. The data obtained in the present research gave evidence
      of the potential of OHD NPs for the targeting and further transfer of genes to
      the epithelial cells.

PMID- 23544544
TI  - Amphiphilic copolymers of sucrose methacrylate and acrylic monomers: bio-based
      materials from renewable resource.
AB  - Regioselective sucrose 1'-O-methacrylate obtained by transesterification
      catalyzed by Proteinase-N was copolymerized with hydrophilic N
      isopropylacrylamide and hydrophobic methyl methacrylate in different molar ratios
      by free radical polymerization. The copolymers were characterized by (13)C
      nuclear magnetic resonance spectroscopy, gel permeation chromatography,
      differential scanning calorimetry and thermogravimetry. Solubility and phase
      behavior of aqueous solutions were also investigated. The glass transition of the
      copolymers presents a positive deviation from the values of the homopolymers due
      to the high density of inter and intramolecular hydrogen bonding. Their
      solubility is strongly dependent on the composition. Copolymers poor in methyl
      methacrylate are water soluble, while copolymers richer in methyl methacrylate
      behaves as hydrogel. These hydrogels are not chemically crosslinked and their
      form can be design prior swelling by the conventional processing methods, such as
      solvent casting and extrusion for instance. Copolymers of N-isopropylacrylamide
      are water soluble and their aqueous solutions present a lower critical solution
      temperature behavior forming thermoreversible hydrogels.

PMID- 23544545
TI  - Anionic ring-opening polymerization of ethylene oxide in DMF with cyclodextrin
      derivatives as new initiators.
AB  - Anionic polymerization initiated by cyclodextrins suffers from a poor solubility
      of those derivatives in standard polymerization solvents. The possibility to
      perform ethylene oxide polymerization initiated by monofunctional initiators
      (allyl alcohol, 2-methoxyethanol) by living ring opening polymerization in DMF, a
      good solvent for any CD derivative, was demonstrated by SEC, (1)H and (13)C NMR
      analyses. The study was extended to the use of native CD as initiator, leading to
      the synthesis of ill-defined structures, explained by the reactivity scale of the
      various hydroxyl functions. Two selectively modified CD derivatives are then used
      to synthesize a new family of star-shaped poly(ethylene oxide) polymers with CD
      core, having 14 or 21 arms. The polymerization was found to be living and DOSY
      experiments confirmed the well-defined structures for the synthesized star
      polymers.

PMID- 23544546
TI  - Structure and antioxidant activity of a novel poly-N-acetylhexosamine produced by
      a medicinal fungus.
AB  - A novel poly-N-acetylhexosamine (polyhexNAc) about 6 kDa average molecular weight
      (MW) was isolated from the low-MW fraction of exopolysaccharide produced by
      liquid fermentation of a medicinal fungus Cordyceps sinensis Cs-HK1. The
      composition and linkage of sugar residues were determined by mass spectrometry
      and methylation analysis, and the anomeric configuration and chain linkage were
      confirmed by NMR. From the analytical results, the molecular structure was
      elucidated as a [-4-beta-D-ManNAc-(1->3)-beta-D-GalNAc-(1->] disaccharide
      repeating unit in the main chain with a Gal branch occurring randomly at the 3
      position of ManNAc. This polyhexNAc showed notable antioxidant activities with a
      Trolox equivalent antioxidant capacity of 330 MUmol Trolox/g, a ferric reducing
      ability of plasma of 45.7 MUmol Fe(II)/g, and significant cytoprotective effect
      against H2O2-induced PC12 cell injury. This is the first report on the structure
      and bioactivity of an extracellular amino-polysaccharide from the Cordyceps
      species.

PMID- 23544547
TI  - Sodium alginate/graphene oxide composite films with enhanced thermal and
      mechanical properties.
AB  - Sodium alginate/graphene oxide (Al/GO) nanocomposite films with different loading
      levels of graphene oxide were prepared by casting from a suspension of the two
      components. The structure, morphologies and properties of Al/GO films were
      characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray
      diffraction (XRD), scanning (SEM) and transmission electron microscopy (TEM),
      thermal gravimetric (TG) analysis, and tensile tests. The results revealed that
      hydrogen bonding and high interfacial adhesion between GO filler and Al matrix
      significantly changed thermal stability and mechanical properties of the
      nanocomposite films. The tensile strength (sigma) and Young's modulus (E) of Al
      films containing 6 wt% GO increased from 71 MPa and 0.85 GPa to 113 MPa and 4.18
      GPa, respectively. In addition, TG analysis showed that the thermal stability of
      Al/GO composite films was better than that of neat Al film.

PMID- 23544548
TI  - Physicochemical and electrokinetic properties of silica/lignin biocomposites.
AB  - A new method of synthesis of novel composites obtained from silica and Kraft
      lignin has been proposed. Silica used in the study was obtained by three methods
      (hydrolysis and condensation of tetraethoxysilane, precipitation in a nonpolar
      and polar medium with the use of sodium silicate). To extend the possible range
      of applications, the silica was preliminary modified with N-2-(aminoethyl)-3
      aminopropyltrimethoxsysilane, and finally it was modified with Kraft lignin
      earlier oxidised with sodium periodate (lignin bonded to SiO2 by covalent
      interactions). The products physicochemical and electrokinetic properties were
      thoroughly analysed. The dispersive properties and surface morphology were
      evaluated on the basis of particle size distributions and SEM images. The
      stability of dispersion in inorganic-organic systems were characterised on the
      basis of the zeta potential, whose value also permitted concluding on the
      interactions between colloidal molecules dispersed in water solutions. The
      products were subjected to elemental analysis to get percentage contents of N, C,
      H, S elements and were also characterised by XPS and FT-IR spectroscopy. Results
      of the study are of practical importance in prospective applications of
      SiO2/lignin biocomposites.

PMID- 23544549
TI  - Aluminium and radiation cross-linked carboxymethyl sago pulp beads for colon
      targeted delivery.
AB  - The carboxymethyl sago pulp (CMSP) with a degree of substitution of 0.4% was
      synthesized from sago waste. The CMSP beads with an average diameter of 3.1-4.8
      mm were formed by aluminium chloride gelation as well as further cross-linked by
      irradiation. To evaluate colon targeted release, a model drug, 5-aminosalicylic
      acid (5-ASA) was encapsulated in CMSP beads. Fourier-transform infrared
      spectroscopy and X-ray diffraction studies indicated intact and amorphous nature
      of entrapped drug. A pH dependent drug release was observed, and about 90% of the
      drug was released only at pH 7.4 over 9 h. Irradiated beads were resisted the
      drug release in an acidic environment at a higher extent than non-irradiated
      beads. The drug release from 6% (w/w) of 5-ASA loaded bead followed zero order,
      whereas, 15 and 22% loaded beads followed first order. The release exponent n
      value suggests non-fickian transport of 5-ASA from the beads.

PMID- 23544550
TI  - Antimicrobial electrospun membranes of chitosan/poly(ethylene oxide)
      incorporating poly(hexamethylene biguanide) hydrochloride.
AB  - Here, antimicrobial nanofibrous membranes were produced by electrospinning of
      chitosan/poly(ethylene oxide) (PEO) solution in the presence of
      poly(hexamethylene biguanide) hydrochloride (PHMB). The influence of PHMB on the
      electrospinnability and antimicrobial properties of chitosan/PEO nanofibers were
      studied. Further, viscosity of the solutions as well as morphology of the
      nanofibrous structures were investigated. Results revealed that incorporation of
      PHMB in chitosan/PEO solutions led to decrease in the zero-shear rate viscosity
      up to 20%. Moreover, increasing PHMB from 0.5 mM to 1 mM led to formation of
      thinner fibers with diameters ranging from 240 nm to 60 nm, respectively. Fourier
      transform infrared (FT-IR) spectrums indicated the functional groups of chitosan,
      PEO and PHMB in nanofibrous structure. Differential scanning calorimetry (DSC)
      thermograms indicated interaction of PHMB with PEO and chitosan through
      alteration in the thermal behavior of the nanofibers. Inhibition of the bacteria
      growth for both Escherichia coli and Staphylococcus aureus were achieved on the
      PHMB loaded nanofibers. Also, a burst release of PHMB from mats has been observed
      in the first hour. These findings suggest that there is a great potential in
      fabrication of biomaterials with incorporation of PHMB using electrospinning.

PMID- 23544551
TI  - Thermal stability and flame resistance of cotton fabrics treated with whey
      proteins.
AB  - It is well described in the literature that whey proteins are able to form
      coatings, which exhibit high mechanical and oxygen barrier properties,
      notwithstanding a great water vapour adsorption. These peculiarities have been
      exploited for applying a novel protein-based finishing treatment to cotton and
      for assessing the protein effect on the thermal and thermo-oxidative stability
      and on the flame retardant properties of the cellulosic fabric. Indeed, the
      deposited whey protein coatings have turned out to significantly affect the
      thermal degradation of cotton in inert and oxidative atmosphere, and to somehow
      modify its combustion when a flame has been applied. Furthermore, the influence
      of the secondary and tertiary structure of these proteins on the morphology of
      the deposited coating, and thus on the thermal and flame retardant properties of
      the treated fabrics, has been evaluated by performing a denaturation thermal
      treatment before the protein application.

PMID- 23544552
TI  - Protective effect of the polysaccharide from Ophiopogon japonicus on
      streptozotocin-induced diabetic rats.
AB  - The present study was designed to investigate the effect of OJP1, a
      polysaccharide isolated from the roots of Ophiopogon japonica, on blood lipid
      metabolism, antioxidant activity, as well as its protective effect on the liver
      and kidneys in diabetic rats. Results showed that OJP1 significantly reduced the
      MDA concentration and increased the activity of both GPx and SOD in the serum,
      liver and kidneys of diabetic rats. Moreover, the values of TG, TC, LDL-C and HDL
      C in diabetic rats were significantly reversed by OJP1 treatment. Biochemical and
      histopathological analyses also showed that OJP1 can alleviate liver and kidneys
      injury in diabetic rats. The mRNA expression of transforming growth factor-beta1
      (TGF-beta1) and connective tissue growth factor (CTGF) in diabetic rats decreased
      significantly after administration of OJP1. Altogether, these results suggest
      that OJP1 possess potent antioxidant activity and can protect the liver and
      kidneys from the injurious effects of diabetes.

PMID- 23544553
TI  - Structure and properties of beta-cyclodextrin/cellulose hydrogels prepared in
      NaOH/urea aqueous solution.
AB  - beta-Cyclodextrin (beta-CD)/cellulose hydrogels were prepared in NaOH/urea
      aqueous solution by crosslinking with epichlorohydrin. The structure and
      morphology of the hydrogels were characterized with Fourier transform infrared
      spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM).
      The swelling test, 5-fluorouracil (5-FU) and bovine serum albumin (BSA), and
      aniline blue (AnB) were used to investigate the swelling capability, drug release
      behavior and the fluorescent property of the hydrogels. The results indicated
      that the swelling degree and water uptake of the hydrogels decreased with an
      increase of the beta-CD content. The in vitro release of 5-FU and BSA of the
      hydrogels showed an inclusion complex formed between 5-FU and beta-CD. beta
      CD/cellulose hydrogels adsorbed AnB lead to a fluorescence enhancement
      attributing to the formation of the host-guest complex between beta-CD and AnB.

PMID- 23544554
TI  - Amphiphilic N-(2,3-dihydroxypropyl)-chitosan-cholic acid micelles for paclitaxel
      delivery.
AB  - Self-assembled amphiphilic N-(2,3-dihydroxypropyl)-chitosan-cholic acid (DHP-CS
      CHO) micelle was prepared as a carrier for paclitaxel. DHP-CS-CHO was synthesized
      by grafted small molecules cholic acid and glycidol onto primary amine group of
      chitosan, respectively. The DHP-CS-CHO formed uniform micelles (size=212.4+/-3.1
      nm) with a low critical micelle concentration (0.024 mg/ml) in PBS. Hydrophobic
      anticancer drug, paclitaxel (PTX), was easily encapsulated into chitosan
      derivative micelles by a dialysis method with loading efficiency up to 80%. The
      PTX loaded micelles released the drug in a sustained manner more than a week in
      PBS containing 0.1% (w/v) Tween 80 at 37 degrees C. In vitro antitumor experiment
      demonstrated that PTX loaded chitosan derivative micelles could inhibit MCF-7
      cell growth and induce its apoptosis. These results suggested that DHP-CS-CHO may
      be a promising carrier for the anticancer drug PTX.

PMID- 23544555
TI  - Improved biosorption potential of Thuja orientalis cone powder for the
      biosorptive removal of Basic Blue 9.
AB  - This study focused on the development of an efficient and practical biosorbent, a
      low cost and promising plant waste with cellulose-lignin polymeric structure, for
      the treatment of dye containing solutions. Thuja orientalis biomass was modified
      by citric acid and its biosorption potential was investigated with respect to pH
      (2.0-10.0), contact time (1-60 min), sorbent dosage (0.01-0.05 g), initial dye
      concentration (10-725 mg L(-1)) and flow rate (0.5-4.0 mL min(-1)). Modification
      significantly increased the biosorption of dye by 30% as compared with unmodified
      biomass. Kinetic data followed the pseudo-second-order model while the
      equilibrium data were well predicted by the Langmuir isotherm model. Maximum dye
      biosorption capacities for natural and modified biomasses were found to be 91.03
      and 203.21 mg g(-1) at 30 degrees C, respectively. Modified biosorbent exhibited
      very good regeneration potential up to 10 cycles and it was successfully used for
      the decolorization of synthetic solution in dynamic flow mode. Zeta potential
      measurements, IR, SEM and EDX analysis were used to characterize the possible dye
      biosorbent interactions. Overall, the present study underlines the alternative
      use of modified T. orientalis cones for removal and recovery applications of
      cationic dye, Basic Blue 9.

PMID- 23544556
TI  - Thermostable, haloalkaline cellulase from Bacillus halodurans CAS 1 by conversion
      of lignocellulosic wastes.
AB  - An extracellular thermostable, haloalkaline cellulase by bioconversion of
      lignocellulosic wastes from Bacillus halodurans CAS 1 was purified to homogeneity
      with recovery of 12.54% and purity fold 7.96 with the molecular weight of 44 kDa.
      The optimum temperature, pH and NaCl for enzyme activity was determined as 60
      degrees C, 9.0 and 30% and it retained 80% of activity even at 80 degrees C, 12
      and 35% respectively. The activity was greatly inhibited by EDTA, indicating that
      it was a metalloenzyme and significant inhibition by PMSF revealed that serine
      residue was essential for catalytic activity. The purified cellulase hydrolyzed
      CMC, cellobiose and xylan, but not avicel, cellulose and PNPG. Furthermore, the
      cellulase was highly stable in the presence of detergents and organic solvents
      such as acetone, n-hexane and acetonitrile. Thus, the purified cellulase from B.
      halodurans utilizing lignocellulosic biomass could be greatly useful to develop
      industrial processes.

PMID- 23544557
TI  - Effects of extractives on some properties of bagasse/high density polypropylene
      composite.
AB  - In this study, the effects of two variable parameters, namely the extractives and
      filler loading level, on the physical properties of composites were examined.
      Composites based on high density polyethylene (HDPE), bagasse flour (BF) as
      filler were made by injection molding. In order to increase the interphase
      adhesion, maleic anhydride grafted polyethylene (MAPE) was added as a coupling
      agent to all the composites studied. Three different solvents, ethanol-benzene,
      1% NaOH and hot-water, were used to remove extractives. Physical properties,
      namely, water absorption (WA) and thickness swelling (TS) were investigated for a
      long period. At same filler loading, composites made with extracted bagasse had
      higher WA and TS values. In addition, the TS of samples showed a similar pattern
      to the water uptake data. The difference in WA between extracted and unextracted
      composites is due to blocking of -OH groups by extractives. The results also
      showed that as the BF content was increased, significant increase in WA and TS
      occurred. Statistical analysis confirmed that the effects of both variables and
      their interactions on the WA and TS properties were significant at 1% confidence
      level.

PMID- 23544558
TI  - Galactosylated chitosan-polycaprolactone nanoparticles for hepatocyte-targeted
      delivery of curcumin.
AB  - Galactosylated chitosan-polycaprolactone (Gal-CH-PCL) copolymers with a
      galactosylation degree of around 10% and varied PCL percentages less than 40 wt%
      were synthesized and used to produce nanoparticles for delivering curcumin. Some
      nanoparticles with encapsulation efficiency of 70% or higher and sizes changing
      from 100 to 250 nm were able to deliver curcumin in a controlled manner. PCL
      content in Gal-CH-PCLs was found to be a key factor for governing the release
      behavior of nanoparticles. Hepatocyte-targeted characteristic of nanoparticles
      was confirmed using human hepatocellular carcinoma (HepG2) cells. In comparison
      to free curcumin, curcumin-loaded Gal-CH-PCL nanoparticles well retained its
      anticancer activity. At an equivalent curcumin-dose of around 20 MUg/mL that was
      found to be relatively safe to human normal liver cells, the results obtained
      from flow-cytometry revealed that some optimized Gal-CH-PCL nanoparticles showed
      more than 6-fold increasing abilities to induce the apoptosis and necrosis of
      HepG2 cells during 72 h treatment compared to free curcumin.

PMID- 23544559
TI  - Superadsorption of LiOH solution on chitosan as a new type of solvent for
      chitosan by freezing/blasting.
AB  - The adsorption behavior and mechanism of chitosan in aqueous LiOH solution was
      studied systemically. The results showed that the adsorption of chitosan was
      mainly due to the breakage of its hydrogen bonds, which were destroyed by the
      reaction of LiOH with the acetyl and the hydroxyl groups of chitosan. Low
      temperature also played a crucial role in the adsorption of chitosan. The
      adsorption of chitosan decreased with increased DD. The adsorption ratio of LiOH
      to chitosan (nLiOH/nCS) increased linearly while the adsorption ratio of water to
      chitosan (n(H2O)/n(CS)) decreased with the increased DD. All chitosans reached
      their maximal swelling degree when the concentration of LiOH was 4.8 wt%.
      Chitosan was stable in LiOH aqueous solution. The LiOH solution may be a
      potential favorable solvent for chitosan.

PMID- 23544560
TI  - PEGylated chitosan complexes DNA while improving polyplex colloidal stability and
      gene transfection efficiency.
AB  - Chitosan is widely explored as a gene delivery vehicle due to its ability to
      condense DNA, facilitate transport, and subsequent release allowing gene
      expression, as well as protecting the DNA. Here, we investigate the enhancement
      of chitosan-DNA dispersion stability while maintaining transfection efficacy by
      PEGylation of chitosan. Molecular properties of fully deacetylated chitosans and
      degree of PEGylation were investigated with respect to compaction of DNA,
      stability and transfection efficacy. Each of the three chitosan samples with
      varying chain lengths was PEGylated at three different degrees. The chitosans
      with degree of PEGylation from 0.6 to 1.9% made polyplexes with DNA. PBS induced
      colloidal aggregation of polyplexes with initial radius of about 100 nm observed
      for nonPEGylated chitosans was suppressed for 1.9% PEGylated chitosans. The
      observed increase in transfection efficacy coinciding with increased polyplex
      colloidal stability suggests that aggregation of gene-delivery packages may
      reduce the transfection efficacy.

PMID- 23544561
TI  - Reversible pH-responsive aggregates based on the self-assembly of functionalized
      POSS and hyaluronic acid.
AB  - We report here the self-assembly of reversible pH intelligent aggregate from
      natural polysaccharide hyaluronic acid and functionalized polyhedral oligomeric
      silsesquioxane with tertiary amines and hydroxyls (POSS-AH). Various forms such
      as micelles, sacs and membranes were self-assembled through different procedures
      in this organic/inorganic hybrid system. The complex can be manipulated simply by
      changing pH to produce hydrogen-bond and ionic interaction. Furthermore the
      aggregates can form at a wide pH range by adjusting the proportion of the two
      constituents. These pH-responsive composites will offer potential opportunities
      in many fields, including cell immune barriers, drug and gene delivery systems
      and chemical sensors.

PMID- 23544562
TI  - pH-responsive sodium alginate-based superporous hydrogel generated by an anionic
      surfactant micelle templating.
AB  - A novel sodium alginate-based superporous hydrogel (SPH) was prepared by the
      grafting copolymerization and micelle templating formed by the self-assembled
      anionic surfactant sodium n-dodecyl sulfonate (SDS). Fourier transform infrared
      (FTIR) spectra demonstrated that SDS was removed from the final hydrogel network.
      The formation mechanism of NaAlg-based SPH was proposed. Effect of SDS
      concentration on the morphologies and pore structure of the hydrogel was
      evaluated by Scanning Electron Microscopy (SEM), and the SDS-1.92 mM sample
      displays homogeneous and well-defined pores, which contribute to improve swelling
      ratio and swelling rate. The time-dependent swelling behaviors of the SDS-1.92 mM
      samples in various salt and pH solutions were investigated. The swelling in
      multivalent salt (Ca(2+), Al(3+))/pH 2 solutions displayed a well-known
      "overshooting effect", whereas, its swelling kinetics in Na(+)/pH 3-12 solutions
      followed Schott's pseudo second-order swelling kinetics model.

PMID- 23544563
TI  - Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for
      controlled release drug delivery.
AB  - A novel interpenetrating polymer network (IPN) microspheres of locust bean gum
      (LBG) and poly (vinyl alcohol) (PVA) was developed for oral controlled release of
      buflomedil hydrochloride (BH) by emulsion crosslinking method using
      glutaraldehyde as crosslinker. The effects of gum-polymer ratio, concentration of
      crosslinker and internal phase viscosity were evaluated thoroughly. Drug
      entrapment efficiency, particle size distribution, swelling property and in vitro
      release characteristics with kinetic modelling of microspheres were evaluated.
      The microspheres were characterised by scanning electron microscopy (SEM),
      Fourier transform infrared spectroscopy (FT-IR), solid state C(13) NMR, X-ray
      diffraction study (XRD) and differential scanning colorimetry (DSC). The
      microspheres showed control release property without showing any incompatibility
      in IPN device. Hence, IPN microspheres of LBG and PVA can be used as a potential
      carrier for controlled oral delivery of highly water soluble drugs like BH.

PMID- 23544564
TI  - Correlations between steric/thermochemical parameters and O-/N-acylation
      reactions of cellulose.
AB  - N(alpha)-t-Butyloxycarbonyl (Boc)-amino acids (Xaa = Gly, Ala, or beta-Ala) were
      reacted with the cellulose hydroxyl groups (O-acylation) using N,N'-carbonyl
      diimidazole. The degrees of substitution toward the total hydroxyl groups
      (DS%(/OH)s) were 38% for O-(Boc-Gly)-Cellulose, 29% for O-(Boc-Ala)-Cellulose and
      53% for O-(Boc-beta-Ala)-Cellulose. The one-by-one N-acylation between the O
      (Xaa)-Celluloses and Boc-Ala-Gly using a water-soluble carbodiimide yielded the
      conjugates N-(Boc-Ala-Gly)-Xaa-Celluloses with DS%(/NH2) values of 25% (Xaa =
      Gly), 35% (Ala), and 48% (beta-Ala), respectively. The results were well
      correlated with DeltaG and DeltaEstrain profiles, which were predicted by semi
      empirical thermochemical parameter calculation coupled with conformer search
      (R(2)>0.90). N-acylation of the O-(beta-Ala)-Cellulose using various length of
      oligo-peptides, Boc-(Ala-Gly)n and Boc-(Gly-Ala)n (where, n = 0.5, 1.0, 1.5, 2.0,
      3.0), suggested that the DS%(/NH2) was dependent on the structural features of
      the symmetric anhydrides as the N-acylating agents, including conformer
      populations and their transition energy.

PMID- 23544565
TI  - Extraction of crude polysaccharides from Gomphidius rutilus and their antioxidant
      activities in vitro.
AB  - Response surface methodology was used to optimize the extraction of crude
      polysaccharides from the fruiting bodies of Gomphidius rutilus. A central
      composite design was adopted to determine the combination of factors (extraction
      time, extraction temperature, extraction frequency, and ratio of water to raw
      material) that resulted in the maximum crude polysaccharide production. Results
      showed that the optimum extraction conditions were as follows: extraction
      temperature, 95 degrees C; ratio of water to raw material, 16; extraction time,
      2.5 h; and extraction frequency, 4. Under these conditions, the experimental
      yield of crude polysaccharides was 8.02+/-0.15%, which well agreed with the
      predicted yield. Evaluation of the antioxidant activity in vitro suggested that
      the crude polysaccharides had high scavenging activity for superoxide anion,
      hydroxyl, and 1,1-diphenyl-2-picrylhydrazyl radicals. The crude polysaccharides
      also showed strong reducing power. Thus, they can be used as natural antioxidants
      in functional foods or medicine.

PMID- 23544566
TI  - Functionalisation of fabrics with conducting polymer for tuning capacitance and
      fabrication of supercapacitor.
AB  - Conducting polymer (polypyrrole (PPy) doped with anion) film has been coated on
      different textile substrates from a mild, room temperature wet in situ chemical
      polymerisation method exploiting pyrrole as a monomer and ferric chloride as an
      oxidant and compared their electrochemical capacitive behaviour by assembling as
      an unit cell supercapacitor. PPy composites were prepared with carbohydrate
      polymers like cotton, linen (Natural cellulosic fibre), modified cellulosic fibre
      viscose rayon and synthetic polymer polyester fabrics to investigate the
      influence on electrochemical capacitance. The surface morphology and chemistry of
      these materials were analysed by SEM, FT-IR, and XRD. It reveals that the PPy has
      greater interaction with the cellulosic fabrics, but whereas surface deposition
      only has taken place with synthetic fibres. The capacitive behaviour of the PPy
      coated textiles were evaluated using cyclic voltammetry, impedance spectroscopy
      and charge-discharge analysis. A unit cell was fabricated to investigate the
      capacitive behaviour by assembling two symmetric textile electrodes separated by
      a solid polymer (PVA/1M H2SO4 gel) electrolyte membrane. The textile electrodes
      prepared with PPy-Cotton and PPy-Viscose exhibited the highest specific
      capacitance value of 268 F g(-1) and 244 F g(-1), respectively at a scan rate of
      5 mV s(-1). The charge-discharge analysis also shows higher specific capacitance
      value for PPy-Viscose and PPy-Cotton. The focus of this research is to highlight
      a successful, simple and reproducible method for fabrication of the textile based
      supercapacitor and the chemistry of surface interaction of PPy molecule with
      natural and synthetic fabrics.

PMID- 23544567
TI  - Effects of thermal, alkaline and ultrasonic treatments on scleroglucan stability
      and flow behavior.
AB  - Aqueous solutions (0.2%, w/v) of scleroglucans from Sclerotium rolfsii ATCC
      201126 from different cultivation time or purification protocol (EPS I, EPS II,
      EPSi) as well as a commercial scleroglucan (LSCL) exhibited different sensitivity
      against thermal (65, 95 and 150 degrees C), ultrasonic (1, 5 and 10 min; 20%
      amplitude) or alkaline (0.01-0.2 N NaOH) treatments. Scleroglucan triple helix
      usually showed signs of denaturation at 150 degrees C or with 0.2 NaOH with a
      pronounced decrease in apparent viscosity and loss of pseudoplastic behavior.
      Differences in sensitivity could be noted depending on the scleroglucan sample,
      which may be likely related to polysaccharide conformational features, and these
      latter to production and/or downstream processing conditions. Transmission
      electron microscopy showed scleroglucan topologies in accordance with thermal and
      alkaline denaturation. Size exclusion chromatography of control scleroglucans
      revealed elution profiles compatible with macromolecular aggregates which tended
      to diminish or disappear as thermal, alkali or sonication treatments progressed.
      Scleroglucan granule dissolution process took ~8-14 s, according to DIC-light
      microscopy, and showed to be facilitated by addition of NaOH.

PMID- 23544568
TI  - A novel and simple procedure to synthesize chitosan-graft-polycaprolactone in an
      ionic liquid.
AB  - An ionic liquid, 1-ethyl-3-methylimidazolium acetate (EMIMAc), was synthesized
      and employed as a homogeneous and green reaction media to prepare chitosan-graft
      polycaprolactone (CS-g-PCL) via ring-opening polymerization, using stannous
      octoate (Sn(Oct)2) as a catalyst. The structures and compositions of copolymers
      could be facilely controlled by the reaction conditions and feed ratios. The
      grafting content of polycaprolactone (PCL) could reach as high as 630%. The
      chemical structures of the copolymers were systematically characterized by (1)H
      NMR, Fourier transform infrared spectroscopy (FTIR) and wide-angle X-ray
      diffraction (WAXD), while thermal properties were studied by thermogravimetric
      analysis (TGA) and differential scanning calorimetry (DSC). The thermal stability
      and glass transition temperature (Tg) of the graft copolymers vary regularly with
      the change of PCL grafting content.

PMID- 23544569
TI  - NMR and rheological study of Aloe barbadensis partially acetylated glucomannan.
AB  - The structural and rheological properties of the Aloe extract (AE) and the
      polysaccharidic fraction (PF) obtained from the leaves pulp of Aloe barbadensis
      Miller were investigated. Structural analyses carried out by composition,
      methylation analysis and NMR spectroscopy showed that PF is mainly constituted by
      a partially acetylated 4-linked beta-d-glucomannan. The acetyl groups are located
      at C-2, C-2 and C-3, C-3 and/or C-6. The acetylation pattern of this type of
      polysaccharide was for the first time established using bidimensional NMR
      analyses. AE and PF aqueous solutions at 25 degrees C showed a non-Newtonian
      behavior (with pseudoplastic characteristics), however PF showed higher apparent
      viscosity than AE. Dynamic oscillatory analyses showed that both samples, at the
      same concentration, behaved as a concentrated solution. PF presented higher
      values of G' compared with those of AE and this behavior could be consequence of
      its higher content in partially acetylated glucomannan.

PMID- 23544570
TI  - Effect of the ionic liquid 1-ethyl-3-methylimidazolium acetate on the phase
      transition of starch: dissolution or gelatinization?
AB  - This work revealed that the interactions between starch, the ionic liquid 1-ethyl
      3-methylimidazolium acetate ([Emim][OAc]), and water might contribute to the
      phase transition (gelatinization, dissolution, or both) of native starch at
      reduced temperature. Using mixtures of water and [Emim][OAc] at certain ratios
      (7.2/1 and 10.8/1 mol/mol), both the gelatinization and dissolution of the starch
      occur competitively, but also in a synergistic manner. At lower [Emim][OAc]
      concentration (water/[Emim][OAc] molar ratio>=25.0/1), mainly gelatinization
      occurs which is slightly impeded by the strong interaction between water and
      [Emim][OAc]; while at higher [Emim][OAc] concentration (water/[Emim][OAc] molar
      ratio<=2.8/1), the dissolution of starch is the major form of phase transition,
      possibly restricted by the difficulty of [Emim][OAc] to interact with starch.

PMID- 23544571
TI  - Adsorption of lignocelluloses of pre-hydrolysis liquor on calcium carbonate to
      induce functional filler.
AB  - In this work, we aimed at adsorbing the oligo-sugars of prehydrolysis liquor on
      precipitated calcium carbonate (PCC) to produce modified PCC. The results showed
      that the adsorptions of oligo-sugars, lignin and furfural were greater on porous
      PCC (PCC2) than on nano-sized PCC (PCC1) due to the larger surface area of PCC2.
      The adsorption reached its maximum in 5 h on PCC1, but it gradually increased on
      PCC2 due to the diffusion of oligo-sugars and lignin into the pores of PCC2.
      Also, the experimental isotherm and kinetic results were well fitted into
      Langmuir and pseudo-second order models, respectively. The adsorption was greater
      at a lower temperature (i.e. 40 degrees C) and pH (i.e. 7). Alternatively,
      cationic poly acrylamide (CPAM) was added to the PHL/PCC system, which led to
      more promising results (than that to PHL/PCC system) with the maximum
      lignocelluloses adsorption of 0.36 g/g on PCC2, among which 0.22 g/g was oligo
      sugars.

PMID- 23544572
TI  - Synthesis of wheat straw cellulose-g-poly (potassium acrylate)/PVA semi-IPNs
      superabsorbent resin.
AB  - To better use wheat straw and minimize its negative impact on environment, a
      novel semi-interpenetrating polymer networks (semi-IPNs) superabsorbent resin
      (SAR) composed of wheat straw cellulose-g-poly (potassium acrylate) (WSC-g-PKA)
      network and linear polyvinyl alcohol (PVA) was prepared by polymerization in the
      presence of a redox initiating system. The structure and morphology of semi-IPNs
      SAR were characterized by means of FTIR, SEM and TGA, which confirmed that WSC
      and PVA participated in the graft polymerization reaction with acrylic acid (AA).
      The factors that can influence the water absorption of the semi-IPNs SAR were
      investigated and optimized, including the weight ratios of AA to WSC and PVA to
      WSC, the content of initiator and crosslinker, neutralization degree (ND) of AA,
      reaction temperature and time. The semi-IPNs SAR prepared under optimized
      synthesis condition gave the best water absorption of 266.82 g/g in distilled
      water and 34.32 g/g in 0.9 wt% NaCl solution.

PMID- 23544573
TI  - Rheological characterization of galactomannans extracted from seeds of
      Caesalpinia pulcherrima.
AB  - The galactomannan from the seeds of Caesalpinia pulcherrima L. was isolated and
      purified by precipitation method using alcohol to get C. pulcherrima (CP) gum. CP
      gum was studied for its physicochemical and rheological properties. The
      composition of CP gum was found to contain mannose:galactose:glucose:xylose in a
      proportion of 2.8:1:0.1:0.08, with M/G ratio 2.80. The molecular weight (Mw) for
      CP gum was obtained to be approximately 2.72*10(6) Da by static light scattering
      measurements and 2.79*10(6) Da using Mark-Houwink relationship. The intrinsic
      viscosity by Huggins and Kraemer plots using capillary viscometry was obtained as
      12-12.5 dl/g. The rheological behavior of aqueous galactomannan solutions was
      studied at 25 degrees C, using steady-shear and dynamic oscillatory measurements.
      The various concentrations of CP gum exhibits shear thinning non newtonian
      behavior at high shear rate and newtonian flow at low shear rate. Experimental
      data in steady shear has been correlated and found a better fitting with the
      Cross and Carreau models. A graph of the specific viscosity at zero shear rate
      (eta(sp0)) against coil overlap parameter (C[eta]) was plotted and the slope of
      the lines in dilute and semi-dilute regions were found to be 1.23 and 4.1
      respectively. The critical concentration (C*) was found to be about 3.8/[eta].
      The linear viscoelastic region for CP gum solutions presented nature as that of
      macromolecular solutions. At all shear rates and frequencies, eta(ap) and eta*
      had almost similar magnitudes, which shows its reasonable agreement with the Cox
      Merz rule. The present investigation shows the suitability of CP gum as a
      pharmaceutical aid application like viscosity modifier, release retardants,
      binders.

PMID- 23544574
TI  - Improvement on the freeze-thaw stability of corn starch gel by the polysaccharide
      from leaves of Corchorus olitorius L.
AB  - Effect of the polysaccharide from leaves of Corchorus olitorius L. (PLC) on the
      freeze-thaw (FT) stability of corn starch gel was studied. PLC was incorporated
      into the starch gel at 0.7% and total solid was adjusted to 6.0%. The syneresis
      was measured by the centrifugal-filtration method and, as a result, addition of
      PLC reduced effectively the syneresis of the starch gel even after 5 FT cycles,
      which was less than one third that of the normal starch gel. The rheological
      changes of the starch/PLC gel during the FT treatments were evaluated while the
      gel remained on the rheometer plate. The starch/PLC gel had less significant
      changes in the rheological parameters during the FT cycles than starch/guar gum
      or xanthan gum gel systems. SEM images showed that PLC stabilized the gel matrix
      surrounding pores, which would contribute to both a lower syneresis production
      and a higher stability in the rheological behavior at FT.

PMID- 23544575
TI  - Hydrolysis of macroalgae using heterogeneous catalyst for bioethanol production.
AB  - Utilization of macroalgae biomass for bioethanol production appears as an
      alternative source to lignocellulosic materials. In this study, for the first
      time, Amberlyst (TM)-15 was explored as a potential catalyst to hydrolyze
      carbohydrates from Eucheuma cottonii extract to simple reducing sugar prior to
      fermentation process. Several important hydrolysis parameters were studied for
      process optimization including catalyst loading (2-5%, w/v), reaction temperature
      (110-130 degrees C), reaction time (0-2.5 h) and biomass loading (5.5-15.5%,
      w/v). Optimum sugar yield of 39.7% was attained based on the following optimum
      conditions: reaction temperature at 120 degrees C, catalyst loading of 4% (w/v),
      12.5% (w/v) of biomass concentration and reaction time of 1.5h. Fermentation of
      the hydrolysate using Saccharomyces cerevisiae produced 0.33 g/g of bioethanol
      yield with an efficiency of 65%. The strategy of combining heterogeneous
      catalyzed hydrolysis and fermentation with S. cerevisiae could be a feasible
      strategy to produce bioethanol from macroalgae biomass.

PMID- 23544577
TI  - Improving wet and dry strength properties of recycled old corrugated carton (OCC)
      pulp using various polymers.
AB  - In this study, the application of different dosages of low and high molecular
      weights (MW) of chitosan (Ch), cationic starch (CS) and poly vinyl alcohol (PVA)
      were systematically investigated using old corrugated carton (OCC) furnishes.
      Various sequences of above-mentioned polymeric additives were also examined to
      find out the optimal combination for improving both wet and dry tensile strength.
      For each treatment, 4 handsheets, each having basis weight of 100 g/m(2), were
      made. In general, the tensile strength of handsheets was significantly affected
      by the addition of polymeric agents. The enhancing effect of additives on dry
      tensile property was much higher than wet condition. The results also showed that
      the tensile strength of the samples made from OCC furnishes were improved upon
      the addition of high molecular weight chitosan (ChI) compared to the untreated
      ones (control). The low MW chitosan did not change the properties of handsheets
      dramatically. Application of polymeric agents moderately decreased the stretch to
      rupture, however with increasing dosage the stretch was improved. Sequential
      addition of used polymers showed that triple application of polymers was
      beneficial to both dry and wet tensile strength, although the effect was larger
      for dry. The best results in wet and dry tensile strengths were achieved using
      sequential of PVA-ChI-CS. Sequential addition of oppositely charged polymers
      forms a macromolecular layered structure of polyelectrolytes.

PMID- 23544576
TI  - Branching pattern of gluco-oligosaccharides and 1.5kDa dextran grafted by the
      alpha-1,2 branching sucrase GBD-CD2.
AB  - GBD-CD2, an engineered sucrose-acting enzyme of glycoside hydrolase family 70,
      transfers D-glucopyranosyl (D-Glcp) units from sucrose onto dextrans or gluco
      oligosaccharides (GOS) through the formation of alpha-(1->2) linkages leading to
      branched products of interest for health, food and cosmetic applications.
      Structural characterization of the branched products obtained from sucrose and
      pure GOS of degree of polymerization (DP) 4 or DP 5 revealed that highly alpha-(1
      >2) branched and new molecular structures can be synthesized by GBD-CD2. The
      formation of alpha-(1->2) branching is kinetically controlled and can occur onto
      vicinal alpha-(1->6)-linked D-Glcp residues. To investigate the mode of branching
      of 1.5 kDa dextran, simulations of various branching scenarios and resistance to
      glucoamylase degradation were performed. Analysis of the simulation results
      suggests that the branching process is stochastic and indicates that the enzyme
      acceptor site can accommodate both linear and poly-branched acceptors. This opens
      the way to the design of novel enzyme-based processes yielding carbohydrate
      structures varying in size and resistance to hydrolytic enzymes.

PMID- 23544578
TI  - Biocompatibility and characterization of renewable agricultural residues and
      polyester composites.
AB  - Composites of sesame husk and glycidyl methacrylate-grafted polytrimethylene
      terephthalate (PTT-g-GMA/SH) exhibit noticeably superior mechanical properties
      compared to PTT/SH composites due to greater compatibility between the two
      components. The dispersion of SH in the PTT-g-GMA matrix is highly homogeneous as
      a result of condensation reaction formations. Human lung fibroblasts (FBs) were
      seeded on these two series of composites to characterize the biocompatibility
      properties. In a time-dependent course, the FB proliferation results demonstrated
      higher performance from the PTT/SH series of composites than from the PTT-g
      GMA/SH composites. In addition, collagen production by FBs present in the PTT/SH
      series was 20% higher than in regular culture-plates after 7 days of incubation.
      The water resistance of PTT-g-GMA/SH was higher than that of PTT/SH, although the
      weight loss of both composites buried in soil compost indicated that they were
      both biodegradable, especially at higher levels of SH substitution. The PTT/SH
      and PTT-g-GMA/SH composites were more biodegradable than pure PTT, implying a
      strong connection between SH content and biodegradability.

PMID- 23544579
TI  - Chemical composition and functional properties of native chestnut starch
      (Castanea sativa Mill).
AB  - Starch isolation methods can change their physico-chemical and functional
      characteristics hindering the establishment of a starch-food functionality
      relation. A simple high yield and soft isolation method was applied for chestnut
      (Castanea sativa Mill) starch consisting in steeping and fruit disintegration in
      a 25 mM sodium bisulfite solution and purification by sedimentation. Starch
      integrity, physico-chemical composition, morphology and functional properties
      were determined, being observed significant differences from previous described
      methods for chestnut starch isolation. The X-ray pattern was of B-type, with a
      degree of crystallinity ranging from 51% to 9%, dependent on the starch moisture
      content. The onset, peak, and conclusion gelatinization temperatures were 57.1
      degrees C, 61.9 degrees C and 67.9 degrees C, respectively. Total amylose content
      was 26.6%, and there was not found any evidence for lipid complexed amylose.
      Swelling power at 90 degrees C was 19 g/g starch, and the amount of leached
      amylose was 78% of the total amylose content. Native chestnut starch presents a
      type B pasting profile similar to corn starch but with a lower gelatinization
      (56.1 degrees C) and peak viscosity (79.5 degrees C) temperatures, making native
      chestnut starch a potential technological alternative to corn starch, especially
      in application where lower processing temperatures are needed.

PMID- 23544580
TI  - Bacterial cellulose and bacterial cellulose-chitosan membranes for wound dressing
      applications.
AB  - Bacterial cellulose (BC) and bacterial cellulose-chitosan (BC-Ch) membranes were
      successfully produced in large scale. BC was synthesized by Acetobacter xylinum.
      BC-Ch was prepared by immersing BC in chitosan followed by freeze-drying. The
      surface morphology of BC and BC-Ch membranes were examined by a scanning electron
      microscope (SEM). SEM images showed that BC-Ch possessed a denser fibril network
      with smaller pores than BC. Infrared spectroscopy was used to confirm the
      incorporation of chitosan in BC-Ch. The swelling behavior, water retention
      capacity, and mechanical properties of BC and BC-Ch were further evaluated.
      Results indicated that both membranes maintained proper moisture contents for an
      extensive period without dehydration. The tensile strength and elongation at
      break for BC-Ch were slightly lower while the Young's modulus was higher. Cell
      culture studies demonstrated that BC and BC-Ch had no cytotoxicity. In the
      antibacterial test, the addition of chitosan in BC showed significant growth
      inhibition against Escherichia coli and Staphylococcus aureus. The effects of BC
      and BC-Ch on skin wound healing were assessed by rat models. Histological
      examinations revealed that wounds treated with BC-Ch epithelialized and
      regenerated faster than those treated with BC or Tegaderm. Therefore, BC-Ch was
      considered as a potential candidate for wound dressing materials.

PMID- 23544581
TI  - A smart approach to add antibacterial functionality to cellulosic pigment prints.
AB  - This study was devoted to enhancing the antibacterial functionality of pigment
      printed cotton, linen and viscose fabrics. Ag-NP's/PVP colloid, triclosan
      derivatives, chitosan or choline chloride was successfully incorporated into the
      pigment paste followed by printing and microwave curing to impart antibacterial
      activity to the cellulosic prints. Results obtained demonstrate that the modified
      pigment prints exhibit a remarkable antibacterial activity against the G+ve
      (Staphylococcus aureus) and G-ve (Escherichia coli) bacteria with a noticeable
      durability after 20 washing cycles without adversely affecting the printing and
      softness properties. The extent of printability and functionality of the
      nominated substrates are significantly governed by the type of: bio-active
      ingredient, binder, pigment and substrate. TEM, SEM and EDX analysis confirmed
      the formation of Ag-NP's/PVP colloid, of particle size range 7-14 nm, deposition
      of cross-linked-binder film onto the modified pigment prints, and the existence
      of elementary Ag and Si loaded onto fabrics surface, respectively.

PMID- 23544582
TI  - Cavitation effect on chitosan nanoparticle size: a possible approach to protect
      drugs from ultrasonic stress.
AB  - The objective of this study was to verify the influence of different modes of
      ultrasonic radiation on both the mean diameter and the polydispersity index (PI)
      of chitosan (CH) nanoparticles, which were prepared by means of the ionotropic
      gelation method. The variations in duration, intensity and mode of cycle of
      ultrasonic radiation allowed us to highlight several optimal treatments in order
      to obtain a potential carrier for site-specific drug delivery. Despite the high
      utility, ultrasound may be a risk factor for sensitive drug-loaded nanoparticles;
      in order to protect the drug from thermal or mechanical stress, the effects of
      ultrasonic radiation only on the CH dispersion (instead of the
      chitosan/tripolyphosphate (TPP) mixture) were studied, without damaging the drug
      added to the TPP solution. The increase of the wave amplitude, mode of cycle and
      time of sonication decreased the particle mean diameter; moreover, the mode of
      cycle showed a greater effect than the other parameters on the PI of the
      nanoparticle system. Both the mean diameter and the PI of CH nanoparticles
      increased with increasing CH concentration. The application of ultrasound only on
      the CH dispersion showed interesting results, particularly in regard to
      formulations prepared from low and medium molecular weight chitosan.

PMID- 23544583
TI  - Microwave superheated water extraction of polysaccharides from spent coffee
      grounds.
AB  - The spent coffee grounds (SCG) are a food industry by-product that can be used as
      a rich source of polysaccharides. In the present work, the feasibility of
      microwave superheated water extraction of polysaccharides from SCG was studied.
      Different ratios of mass of SCG to water, from 1:30 to 1:5 (g:mL) were used for a
      total volume of 80 mL. Although the amount of material extracted/batch (MAE1)
      increased with the increase of the concentration of the sample, the amount of
      polysaccharides achieved a maximum of 0.57 g/batch for 1:10. Glycosidic-linkage
      composition showed that all extraction conditions allowed to obtain mainly
      arabinogalactans. When the unextracted insoluble material was re-extracted under
      the same conditions (MAE2), a further extraction of polysaccharides was observed
      (0.34 g/batch for 1:10), mainly galactomannans. Also, a high amount of
      oligosaccharides, mainly derived from galactomannans, can be obtained in MAE2
      (0.96 g/batch for 1:10). This technology allows to obtain galactomannans and
      arabinogalactans in proportions that are dependent on the operating conditions.

PMID- 23544584
TI  - Construction of hyaluronic acid noisome as functional transdermal nanocarrier for
      tumor therapy.
AB  - To develop a functional nanosized transdermal drug delivery system for tumor
      therapy, amphiphilic hyaluronic acid (HA) based niosome was constructed combining
      transdermal and tumor targeting ability in one entity. HA esterified with
      monostearin, the conjugate labeled as HA-GMS self-assembled onto niosome surface
      and formed HA-niosome. The multilayer vesicle had small size (around 40 nm), good
      stability and desirable drug encapsulating efficacy, and well compatible with
      blood. It exhibited better endocytosis to mouse breast tumor cell (4T1) than the
      control chitosan nanoparticle, which was verified qualitatively and
      quantitatively. Skin permeation of HA-niosome was proven to be efficient using in
      vitro stratum corneum model and in vivo fluorescence observation. Histological
      section study confirmed the security and efficiency of transdermal permeation.
      The results evidence HA-niosome to be exciting and promising for tumor therapy
      through trandermal administration.

PMID- 23544585
TI  - Direct fluorination applied to wood flour used as a reinforcement for polymers.
AB  - Direct fluorination was applied to wood flour in order to improve its
      compatibility with polymers and thus enhance the properties of wood-polymer
      composites. Fourier-transform infrared spectra and (19)F solid-state nuclear
      magnetic resonance results underlined a successful covalent grafting of fluorine
      atoms onto the wood chemical structure. No physical damage of the wood particles
      was observed during scanning electron microscopy analysis. The thermal behaviour
      of the wood flour was also studied by thermogravimetric analysis. The hydrophilic
      property changes of wood flour were examined by evaluating the water content and
      the rate of water uptake of samples under different relative humidity conditions.
      A decrease in the wood flour water content was noted after fluorination. All
      these studies tend to prove the efficiency of this treatment on wood hydrophilia.

PMID- 23544586
TI  - A heparin-like compound isolated from a marine crab rich in glucuronic acid 2-O
      sulfate presents low anticoagulant activity.
AB  - A natural heparin-like compound isolated from the crab Goniopsis cruentata was
      structurally characterized and its anticoagulant and hemorrhagic activities were
      determined. Enzymatic and nuclear magnetic resonance analysis revealed that its
      structure is rich in disulfated disaccharides, possessing significant amounts of
      2-O-sulfated-beta-D-glucuronic acid units. Furthermore, low amounts of
      trisulfated disaccharide units containing 2-O-sulfated-alpha-L-iduronic acid were
      detected, when compared to mammalian heparin. In addition, this heparin-like
      structure showed negligible in vitro anticoagulant activity and low bleeding
      potency, facts that make it a suitable candidate for the development of structure
      driven, heparin based therapeutic agents with fewer undesirable effects.

PMID- 23544587
TI  - Structure and properties of polypyrrole/bacterial cellulose nanocomposites.
AB  - An electrically conducting composite based on bacterial cellulose (BC) and
      polypyrrole (PPy) was prepared through in situ oxidative polymerization of
      pyrrole (Py) in the presence of BC membrane using ammonium persulfate (APS), as
      an oxidant. The electrical conductivity, morphology, mechanical properties and
      thermal stability of the composites obtained using APS (BC/PPy.APS) were
      evaluated and compared with BC/PPy composites prepared using as oxidant agent
      Iron III chloride hexahydrate (FeCl3.6H2O). The morphology of the BC/PPy.APS
      composites is characterized by spherical conducting nanoparticles uniformly
      distributed on the BC nanofiber surface, while the composites produced with
      FeCl3.6H2O (BC/PPy.FeCl3) is composed of a continuous conducting polymer layer
      coating the BC-nanofibers. The electrical conductivity of BC/PPy.FeCl3 was 100
      fold higher than that found for BC/PPy.APS composites. In order to understand the
      site-specific interaction between PPy and BC functional groups, both composites
      were characterized by Fourier transform infrared (attenuated total reflectance
      mode) spectroscopy attenuation reflectance (FTIR-ATR) and X-ray photoelectron
      spectrometry (XPS). The affinity between functional groups of PPy.FeCl3 and BC is
      higher than that found for BC/PPy.APS composite. In addition, the tensile
      properties were also influenced by the chemical affinity of both components in
      the polymer composites.

PMID- 23544588
TI  - Synthesis of gas barrier starch by dispersion of functionalized multiwalled
      carbon nanotubes.
AB  - Nanocomposite films were prepared successfully by simple solution casting method
      from plasticized starch/functionalized multiwalled carbon nanotubes (PS/f
      MWCNTs). The interaction of starch with functionalized multiwalled carbon
      nanotube (f-MWCNT) was evidenced by ultraviolet-visible (UV-vis) spectroscopy and
      Fourier transforms infrared (FTIR) spectroscopy. The morphological and thermal
      properties of the composite films were investigated using scanning electron
      microscope (SEM), high resolution transmission electron microscope (HRTEM), X-ray
      diffraction (XRD) and thermo gravimetric analysis (TGA). The electrical
      conductivity of the composites was increased significantly by sixteen times, from
      0.1*10(-9) to 1.6*10(-9) S/cm. This reveals better dispersion of f-MWCNT with low
      concentration of f-MWCNT. The oxygen permeability of the composites was reduced
      by half as compared to virgin PS. This indicates better dispersion of f-MWCNT in
      PS matrix due to formation of strong hydrogen bonding with PS matrix.

PMID- 23544589
TI  - A comparative study of chitosan shielding effect on nano-carriers hydrophilicity
      and biodistribution.
AB  - Engineering polymer surfaces reduces nanoparticles (NPs) aggregation and
      phagocytosis due to effective shielding, hindering recognition by the
      reticuloendothelial system (RES). The shielding of NPs is complex and affected by
      the type of groups used in terms of charge and hydrophilicity. This will, in
      turn, affect NPs biodistribution which will determine the length of activity of
      the drug. Polysaccharides are nowadays recognized for decreasing the uptake of
      particulate carriers by the mononuclear phagocytic system (MPS). Chitosan is
      considered as an attractive candidate due to its biocompatibility,
      biodegradability, non-toxicity and low cost. In this study clozapine (CZP)-loaded
      NPs were coated with chitosan, pluronic F-68, polyethylene glycol (PEG) 4000 and
      polysorbate 80. The factors affecting drug encapsulation efficiency, particle
      size, surface charge, surface hydrophilicity, pharmacokinetics and
      biodistribution were studied. The results proved that although a similarity in
      surface hydrophilicity, chitosan-stealth NPs showed different pharmacokinetic
      profile and biodistribution behavior compared to polysorbate-stealth NPs.

PMID- 23544590
TI  - In situ preparation of silver nanocomposites on cellulosic fibers--microwave vs.
      conventional heating.
AB  - A green approach for the preparation of silver nanocomposites on viscose fibers
      using microwave and conventional heating is presented. Reduction of silver
      nitrate is induced by addition of 6-O chitosan sulfate (S-Chi) in aqueous media
      which provides steric protection and electrostatic stabilization to prevent
      agglomeration of the nanoparticles. The particles are formed in close spatial
      proximity to the fibers and adsorption of the particles via structural similarity
      takes place to create silver nanocomposites. All nanocomposites have been
      subjected to antimicrobial tests and high antimicrobial activity toward
      Escherichia coli bacteria has been determined. Further, the nanocomposites are
      characterized using different analytical techniques which reveal very similar
      results for both heating techniques. The only significant difference is observed
      concerning the shape of the nanoparticles on the viscose fibers which are
      slightly elongated for the microwave method in comparison to spheres observed by
      conventional heating. Therefore, detailed investigations on the formation of
      colloidal silver nanoparticles have been performed, comparing microwave
      dielectric and conventional heating at the exact same temperature and reaction
      times. These experiments resulted in nearly identical nanoparticle shape and size
      for both heating methods as demonstrated by dynamic light scattering, UV-vis
      spectroscopy and transmission electron microscopy. A wide range of parameters has
      been varied (temperature, AgNO3 to S-Chi ratio, reaction time, and stirring
      speed) to study the nanoparticle formation under microwave and conventional
      conditions. No evidence for the existence of so-called specific microwave effects
      was obtained.

PMID- 23544591
TI  - Use of polysaccharide based surfactants to stabilize organically modified clay
      particles aqueous dispersion.
AB  - Pure as well as organically modified clay minerals are widely applied particles
      in different research areas. For the incorporation of hydrophobic organically
      modified clay particles into the hydrogel matrix, a stable aqueous dispersion
      must be prepared. In this article we report on the stabilization of aqueous
      dispersions of hydrophobic organically modified clay particles by using a non
      ionic polysaccharide-based surfactant system-Inutec SP1 (based on chicory
      inulin). Different concentrations of surfactants were tested. Properties of the
      particulate surfactant-stabilized aqueous colloidal system were determined by
      electrophoretic mobility and dynamic light scattering measurements. Determination
      of contact angles gave us insight into the particles' surface interaction ability
      with water and also some information regarding the conformation of adsorbed
      surfactant molecules on the particle surface. By using Inutec SP1, the
      wettability of clay particles was improved, particle size was reduced and
      consequently, enhancement of their dispersion ability in water-based systems was
      observed.

PMID- 23544592
TI  - Chitosan-gellan electrostatic complexes: influence of preparation conditions and
      surfactant presence.
AB  - Nanoparticles were obtained by electrostatic complexation between chitosan and
      gellan gum at different polysaccharide ratios. The effect of the chitosan:gellan
      ratio on the particle charge and particle size distribution was determined by
      dynamic light scattering measurements. The particle stability was studied during
      storage in an aqueous medium at 25 degrees C for 100 h. The effect of the
      preparation procedure (mixing steps) on the characteristics of the complexes was
      also determined. In addition, the influence of a nonionic surfactant (polysorbate
      20) on the chitosan:gellan electrostatic complexes (PECs) was evaluated. The
      charge of the PECs depended on the polysaccharide ratio. During storage,
      structural reorganization of the complexes was observed. The mixture protocol was
      a determinant factor for PEC size. Multilayered particles formed by a 2-step
      mixing of polysaccharide solutions showed a considerable increase in size as
      compared to the complexes formed by a 1-step mixing. The PEC size, count rate and
      zeta potential were not affected by the presence of polysorbate-20.

PMID- 23544593
TI  - Structural characterization of a glucuronoarabinoxylan from pineapple (Ananas
      comosus (L.) Merrill) gum exudate.
AB  - Native polysaccharide from pineapple gum (PANP) was obtained following alkaline
      extraction of gum and fractionation with cetylpyridinium chloride. It was
      characterized as a glucuronoarabinoxylan using NMR, methylation data, controlled
      Smith degradation, carboxy-reduction, and ESI-MS of oligosaccharides produced on
      mild acid hydrolysis of PANP. HSPEC-MALLS-RI of carboxy-reduced fraction showed
      homogeneous profile (Mw 1.943*10(5) g/mol). PANP was composed of Ara, Xyl, Gal,
      and GlcpA (40:23:7:30 molar ratio). Its main chain presented (1->4)-linked beta
      xylan, highly substituted at O-2 and O-3 by side chains of 3-O- and 3,5-di-O
      linked alpha-Araf, 2-O- and 4-O-linked alpha-GlcpA, and nonreducing end-units of
      alpha-Araf, beta-Arap, beta-Galp, and alpha-GlcpA. ESI-MS of a mixture of
      oligosaccharides formed on the mild acid hydrolysis of PANP was consistent with
      repetitive structures of alpha-GlcpA O-3 linked at beta-Xylp units, whereas in
      others glucuronoarabinoxylan-type gum exudates, alpha-GlcpA units had been
      previously found to be linked at O-2.

PMID- 23544594
TI  - Aneuploidy characterizes adjacent non-malignant mucosa of ulcerative colitis
      associated but not sporadic colorectal carcinomas: a matched-pair analysis.
AB  - INTRODUCTION: Aneuploidy has been suggested as independent prognostic marker in
      ulcerative colitis (UC) patients for developing UC-associated colorectal
      carcinomas (UCCs). UCCs are associated with a poorer prognosis and more
      frequently present with synchronous carcinomas when compared with sporadic
      colorectal carcinomas (SCCs). The authors therefore investigated if the adjacent
      non-malignant mucosa of aneuploid UCCs and aneuploid SCCs shows differences
      regarding the frequency of aneuploidy and if this aneuploidy is associated with
      histomorphological alterations. METHODS: Primary tumors of 25 UCCs and 20 SCCs
      were selected showing exclusively aneuploid DNA patterns and matching DNA
      stemlines. The UCCs' (n = 82) and SCCs' (n = 40) adjacent non-malignant mucosa
      were evaluated for histopathology and assessed for DNA ploidy status by image
      cytometry. RESULTS: UCCs' non-malignant mucosa showed dysplasia in 31.7% and
      aneuploidy in 89%. In contrast, SCCs' non-malignant mucosa revealed no dysplasia
      and aneuploidy in only 5%. Irrespective of dysplastic lesions, aneuploidy was
      observed more frequently in adjacent non-malignant mucosa of UCCs than of SCCs (p
      < 0.001). Neither a correlation between aneuploidy and inflammation (p = 0.916)
      nor between aneuploidy and dysplastic lesions (p = 0.159) could be observed.
      CONCLUSION: Aneuploidy is more frequent in adjacent non-malignant mucosa of
      aneuploid UCCs than in adjacent non-malignant mucosa of aneuploid SCCs.
      Furthermore, aneuploidy seems to be irrespective of inflammation or dysplasia.
      The results therefore emphasize the importance of aneuploidy for UC-associated
      carcinogenesis and its potential as new diagnostic target.

PMID- 23544596
TI  - Pup odor and ultrasonic vocalizations synergistically stimulate maternal
      attention in mice.
AB  - Pup ultrasonic vocalizations (USVs), which are emitted by hypothermic pups, and
      pup odor are thought to be triggers of maternal behavior in mice. We investigated
      whether pup odor stimulated maternal responses to pup USVs in mother C57BL/6
      mice. Two-choice tests were conducted by introducing mothers into a test cage in
      which a tube was attached on each long wall, and the duration spent in each tube
      was compared. Pup USVs were reproduced by an ultrasonic speaker at the tube end.
      In some cases, cotton with pup odor was also presented at the end of the tube.
      Compared to no stimuli, mothers did not specifically approach the sole
      presentation of either reproduced pup USVs or pup odor. However, compared to the
      sole presentation of pup odor, the simultaneous presentation of pup USVs and odor
      induced a specific approach response. These results suggested that pup USVs and
      odor synergistically stimulated maternal behavior. In addition, it was confirmed
      that mothers approached hypothermic pups emitting pup USVs for longer than
      anesthetized silent pups. To investigate the underlying neural mechanisms, we
      observed neural responses to various stimuli with the immunohistochemistry of c
      fos expression. In the bed nucleus of the stria terminalis, the medial preoptic
      area, the central nucleus of the amygdala, and the basolateral amygdala, the
      numbers of c-fos-positive cells were significantly increased following the
      simultaneous presentation of pup USVs and odor compared to the presentation of
      each alone, suggesting that these nuclei were involved in multimodal processing
      related to maternal behavior.

PMID- 23544595
TI  - Modulation of male song by naloxone in the medial preoptic nucleus.
AB  - Studies in songbirds implicate opioid neuropeptides in singing behavior; however,
      past results are contradictory. In starlings, the effect of opioid manipulations
      on sexually motivated courtship song differed in birds naturally singing at low
      compared to high rates, and mu-opioid receptors were denser in several regions,
      including the medial preoptic nucleus (POM) in low singing males. In the present
      study, we found that low singing male starlings also had significantly higher
      enkephalin (ENK) immunolabeling densities in the POM than high singers. We
      blocked opioid receptor activity in the POM with naloxone injections and found
      that this increased both song rate and song bout length in low singers,
      suggesting that high densities of mu receptors and ENK in the POM actively
      suppress song in these males. In contrast to its effects on low singers, naloxone
      in the POM of high singers dose dependently decreased song rate and tended to
      reduce song bout length. This suggests that at least some level of opioid
      activity in POM is necessary for song production. Our results are the first to
      demonstrate that direct administration of naloxone into the POM influences
      sexually motivated song, and that effects differ depending on an individual's
      initial rate of song and associated density of ENK. We suggest that differential
      effects seen in past studies of opioids and song may in part be explained by
      differences in the natural song rate of subjects and accompanying differences in
      ENK activity and neural substrate sensitivity to opioids in POM.

PMID- 23544597
TI  - Endogenous opioids mediate the sexual inhibition but not the drug
      hypersensitivity induced by sexual satiation in male rats.
AB  - Ejaculation promotes endogenous opioid release. Copulation to exhaustion produces
      several enduring behavioral and physiological changes, among which a long-lasting
      sexual behavior inhibition and generalized drug hypersensitivity are the most
      conspicuous. Because copulation to exhaustion involves multiple successive
      ejaculations, in this work we hypothesized that the endogenous opioids released
      by multiple ejaculations during the copulation to exhaustion process might
      mediate the abovementioned sexual satiation-induced changes. To test this
      hypothesis, sexually experienced male rats were injected with the opioid receptor
      antagonist naltrexone before copulation to exhaustion and were tested for sexual
      behavior or drug hypersensitivity 24 h later. The latter was assessed by the
      appearance of the flat body posture sign of the serotonergic syndrome, in
      response to doses of the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist 8
      hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT), lower than those normally
      inducing this sign. The effect of administering naltrexone to already sexually
      exhausted animals (i.e., 24 h after the sexual satiation process) on both
      responses was also tested. Results showed that endogenous opioids mediate the
      establishment and maintenance of the long-lasting sexual behavior inhibition but
      not the drug hypersensitivity (to 8-OH-DPAT) characteristic of sexually exhausted
      male rats. It is concluded that although both phenomena appear as a consequence
      of copulation to satiation and follow a same time course of recovery, they are
      produced by distinct mechanisms.

PMID- 23544598
TI  - Paradoxical effects of stress and an executive task on decisions under risk.
AB  - In everyday life, decisions are often made under stress and while being occupied
      with multiple tasks. It has recently been shown that acute stress impairs
      decision making under risk. Performing a parallel executive task also caused
      riskier decision making. To investigate the effects of a combination of these two
      factors on decision making, we conducted a large (N = 126) experimental study
      with a 2 * 2 design (stress vs. no stress and parallel task vs. no parallel
      task). Stress was induced using the Trier Social Stress Test (TSST) and controls
      underwent the placebo TSST. Salivary samples were collected to assess cortisol
      and alpha amylase concentrations as markers of the two stress response systems.
      Decision making was measured using the Game of Dice Task (GDT). A 2-back task
      served as parallel executive task. Our results revealed a significant interaction
      between stress and the parallel executive task. In line with our earlier
      findings, acute stress and a parallel executive task individually tended to
      impair decision making under risk, manifested by more high risky than low risky
      choices. Interestingly, stressed participants in the parallel-task condition (GDT
      plus 2-back) showed similar decision-making behavior as nonstressed single-task
      participants. Regression analyses revealed executive functions to moderate stress
      effects on decisions under risk. Reasons for these paradoxical findings are
      discussed with respect to stress-evoked cognitive alterations that may benefit
      decision making under risk, if an executive task is performed simultaneously.

PMID- 23544601
TI  - Phospholipase A2 inhibitors isolated from medicinal plants: alternative treatment
      against snakebites.
AB  - Many plants are used in traditional medicine as active agents against various
      effects of snake bites. Phospholipase A2 enzymes are commonly found in venoms of
      snakes of the Viperidae and Elaphidae families, which are their main components.
      This article presents an overview of inhibitors isolated from plants, which show
      antiophidian properties. 

PMID- 23544599
TI  - Compared with DBA/2J mice, C57BL/6J mice demonstrate greater preference for
      saccharin and less avoidance of a cocaine-paired saccharin cue.
AB  - Rats avoid intake of a saccharin cue when paired with a drug of abuse. While this
      is true for most subjects, the degree of avoidance of the drug-paired cue depends
      upon many factors including an individual rat's preference for rewards. That
      said, the direction of this effect is complex. For example, reward-preferring
      Lewis rats exhibit greater cocaine-induced avoidance of a saccharin cue relative
      to Fischer 344 rats; while reward-preferring mice that overexpress DeltaFosB (NSE
      tTA * TetOp-DeltaFosB) exhibit less avoidance of the drug-paired taste cue
      compared to controls. The aim here was to use two strains of commonly used mice,
      C57BL/6J and DBA/2J, to determine whether known differences in sensitivity to
      rewards will facilitate or attenuate drug-induced suppression of intake of a drug
      paired taste cue. The results of Experiment 1 demonstrate that C57BL/6J mice,
      compared with DBA/2J mice, exhibit attenuated suppression of saccharin intake
      when it is paired with cocaine. The results of Experiment 2 demonstrate that
      strain differences in impulsivity are not likely to account for these
      differences. It is proposed that, while the C57BL/6J mice typically are more
      responsive to drug, they also are more responsive to natural rewards (in this
      case saccharin), and the stronger preference for saccharin serves to militate
      against drug.

PMID- 23544600
TI  - Two functional serotonin polymorphisms moderate the effect of food reinforcement
      on BMI.
AB  - Food reinforcement, or the motivation to eat, has been associated with increased
      energy intake, greater body weight, and prospective weight gain. Much of the
      previous research on the reinforcing value of food has focused on the role of
      dopamine, but it may be worthwhile to examine genetic polymorphisms in the
      serotonin and opioid systems as these neurotransmitters have been shown to be
      related to reinforcement processes and to influence energy intake. We examined
      the relationship among 44 candidate genetic polymorphisms in the dopamine,
      serotonin, and opioid systems, as well as food reinforcement and body mass index
      (BMI) in a sample of 245 individuals. Polymorphisms in the monoamine oxidase A
      (MAOA-LPR) and serotonin receptor 2A genes (rs6314) moderated the effect of food
      reinforcement on BMI, accounting for an additional 5-10% variance and revealed a
      potential role of the single nucleotide polymorphism, rs6314, in the serotonin 2A
      receptor as a differential susceptibility factor for obesity. Differential
      susceptibility describes a factor that can confer either risk or protection
      depending on a second variable, such that rs6314 is predictive of both high and
      low BMI based on the level of food reinforcement, while the diathesis stress or
      dual-gain model only influences one end of the outcome measure. The interaction
      with MAOA-LPR better fits the diathesis stress model, with the 3.5R/4R allele
      conferring protection for individuals low in food reinforcement. These results
      provide new insight into genes theoretically involved in obesity, and support the
      hypothesis that genetics moderate the association between food reinforcement and
      BMI.

PMID- 23544602
TI  - Computational methods in determination of pharmacophore models of 5-HT(1A), 5
      HT(2A) and 5-HT(7) receptors.
AB  - The present paper discusses models of 5-HT(1A) and 5-HT(2A) receptors, developed
      by conformational analysis and 3D-QSAR methods. Hypotheses concerning the ligand
      5-HT(7) receptor interaction were complemented by models constructed on the basis
      of the receptor's structure. Various pharmacophore concepts are supported by
      structures of exemplary ligands and groups of compounds, derived from chain
      polycyclic arylpiperazines, used for models generations.

PMID- 23544603
TI  - Novel research strategies of benzimidazole derivatives: a review.
AB  - Benzimidazole plays an important role in the medicinal chemistry and drug
      discovery with many pharmacological activities which have made an indispensable
      anchor for discovery of novel therapeutic agents. Substitution of benzimidazole
      nucleus is an important synthetic strategy in the drug discovery process.
      Therapeutic properties of the benzimidazole related drugs have encouraged the
      medicinal chemists to synthesize novel therapeutic agents. Therefore, it is
      required to couple the latest information with the earliest information to
      understand the current status of benzimidazole nucleus in drug discovery. In the
      present review, benzimidazole derivatives with different pharmacological
      activities are described on the basis of substitution pattern around the nucleus
      with an aim to help medicinal chemists for the development of SAR on
      benzimidazoles for each activity. This article aims to review the work reported,
      chemistry and pharmacological activities of benzimidazole derivatives during past
      years. 

PMID- 23544604
TI  - Pyrazolines: a biological review.
AB  - Pyrazoline is an important five membered nitrogen heterocycle, which has been
      extensively researched upon. The ring is quite stable and has inspired chemists
      to carry out various structural variations in the ring. This has propelled the
      development of distinct pyrazolines with an array of pharmacological activities
      viz. anti-inflammatory, analgesic, antimicrobial, anticancer, antidepressant etc.
      The review aims at highlighting this pharmacological diversity of pyrazolines.
      The review is a gist of latest work done describing the pharmacological aspects
      and potential of pyrazoline ring.

PMID- 23544605
TI  - MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4
      mediated apoptosis.
AB  - PURPOSE: The participation of microRNAs (miRNAs) in cardiovascular diseases
      suggests them as potential targets for novel preventive and therapeutic
      strategies. In this study, the key myocardial miRNA, miR-21, was identified in
      the murine coxsackievirus B3 (CVB3)-induced myocarditis model and its
      contribution to disease progression was explored. METHODS: Myocardial microRNA
      expression changes in CVB3-infected mice were analyzed by real-time PCR and miR
      21 was found to be the miRNA whose expression was significantly reduced. Mice
      were injected with plasmid encoding miR-21 (pMDH-miR-21) at day 1 post CVB3
      infection and myocarditis severity was evaluated 7 days post-infection. The
      underlying mechanism of miR-21 in viral myocarditis was also investigated.
      RESULTS: Myocardial miR-21 expression was negatively related to viral myocarditis
      severity. Recovery of miR-21 expression, by injecting with pMDH-miR-21,
      significantly relieved CVB3-induced myocarditis as shown by increased body
      weight, reduced myocardial injury, lowered myocarditis score and increased
      survival rate. Further study showed that miR-21 could protect myocardial
      apoptosis by specifically inhibiting its target programmed cell death 4 (PDCD4)
      expression. CONCLUSION: miR-21 administration efficiently alleviated CVB3-induced
      myocarditis by repressing PDCD4-mediated apoptosis. Our study not only helps to
      better understand the pathogenesis of viral myocarditis, but also proves the
      potential of miR-21 as a novel therapeutic target for treatment of CVB3-induced
      myocarditis and other apoptosis-mediated cardiovascular diseases.

PMID- 23544606
TI  - Dismantling sociocultural barriers to eye care with tele-ophthalmology: lessons
      from an Alberta Cree community.
AB  - PURPOSE: There are significant disparities in access to health care amongst
      Aboriginal Canadians. The purpose of this study was to determine whether tele
      ophthalmology services, provided to Aboriginal Canadians in a culturally
      sensitive community-based clinic, could overcome social and cultural barriers in
      ways that would be difficult in the traditional hospital-based setting. METHODS:
      The Aboriginal Diabetes Wellness Program of Alberta incorporates culturally
      sensitive health-related activities and rituals as a component of a diabetic
      retinopathy tele-ophthalmology screening program. Metrics of program attendance
      were collected while stakeholders participated in a survey to identify barriers
      to healthcare delivery. RESULTS: Aboriginal patients, cultural liaison, nurses
      and program administrators revealed economic, geographic, social and cultural
      barriers to healthcare faced by Aboriginal people. It was found that the
      introduction of culturally-sensitive programs led to increased appointment
      attendance; from 25% to 85%. Involvement of Aboriginal nurses, inclusion of
      culturally-sensitive activities and participation in spiritual ceremonies led to
      qualitative accounts of increased patient satisfaction, trust towards the
      healthcare team and communication amongst participants. CONCLUSIONS: A culturally
      sensitive model of healthcare delivery in a community-based health clinic
      improved access to tele-ophthalmology services. This was demonstrated by
      increased attendance at appointments and increased satisfaction amongst patients.

PMID- 23544607
TI  - Interferon-gamma and interleukin-17 production from PPD-stimulated PBMCss of
      patients with pulmonary tuberculosis.
AB  - PURPOSE: The purpose of this study was to evaluate Interferon (IFN)-gamma and
      Interleukin(IL)-17 profiles in patients with different clinical presentations of
      pulmonary tuberculosis (TB) and to compare them with those of tuberculin-negative
      and tuberculin-reactive healthy controls METHODS: Peripheral blood mononuclear
      cells (PBMCss), isolated from patients (n=52) and controls (n=30), were
      stimulated ex vivo with purified protein derivative (PPD) and IFN-gamma and IL-17
      levels in the supernatant were measured. RESULTS: At baseline, PBMCss from
      patients with TB released a significantly lower amount of IL-17 (p=0.043) than
      PBMCss from healthy controls, whereas IFN-gamma levels were similar in the two
      groups. After PPD stimulation, a significant rise in IL-17 levels was found only
      among healthy controls (p=0.02). This rise in IL-17 levels was similar between
      tuberculin-reactive and tuberculin-negative subjects. After PPD stimulation,
      patients with infiltrative TB secreted higher levels of IL-17 and IFN-gamma than
      those affected with chronic, miliary and cavitary TB (p < 0.01). IFN-gamma
      production from patients with infiltrative TB was even higher than for healthy
      controls (p < 0.01). PBMCss from tuberculin-reactive patients released higher
      levels of IFN-gamma than tuberculin-negative subjects after PPD stimulation (p <
      0.01). CONCLUSION: Ex vivo PPD stimulation of PBMCs from patients with pulmonary
      TB does not significantly stimulate IL-17 release; however, higher IL-17 and IFN
      gamma levels are found in patients with infiltrative disease, in comparison with
      those affected with miliary, cavitary and chronic TB.

PMID- 23544608
TI  - Pancreatic islet cell autophagy during aging in rats.
AB  - PURPOSE: Autophagy induces pancreatic beta cell death. The purpose of the present
      study was to examine the hypothesis that the extent of pancreatic autophagy is
      associated with aging and age-related diabetes. METHODS: Pancreatic tissue and
      blood samples were collected from Sprague Dawley rats receiving a normal diet at
      2 (the young group), 6 (the adult group), 12 (the middle-age group) and 20-24
      (the aged group) months of age. Body weight and fasting blood glucose, serum
      lipid levels and serum insulin levels were determined. Pancreatic cell structure
      and autophagy were determined using transmission electron microscopy of rats at
      6, 12 and 24 months of age. Lamp2 and LC3b protein expression levels were
      determined by both immunohistochemistry and Western blot analyses, and islet cell
      apoptosis was assessed using the TUNEL assay. RESULTS: Fasting blood glucose,
      triglyceride and FFA levels increased significantly with age (p < 0.05). Compared
      with levels seen in two-month-old rats, insulin secretion of islet cells in vitro
      was significantly reduced at 6, 12, and 20 months of age (p < 0.05).
      Autophagosomes were only observed in islet cells of 24 month-old rats. Increased
      expression of the autophagic markers, Lamp2 and LC3b, was observed with age. A
      significant increase in apoptotic index was observed between young rats (two
      months-old) and older rats (six-, 12- and 24-months-old), but no differences were
      observed between rats six, 12 and 24 months of age. CONCLUSION: Appearance of
      autophagosomes and increased Lamp2 and LC3b expression in pancreatic islet cells
      coincided with a significant decrease in insulin secretion and elevation of
      fasting blood glucose in aged rats.

PMID- 23544609
TI  - Significance of CAVI, hs-CRP and homocysteine in subclinical arteriosclerosis
      among a healthy population in China.
AB  - PURPOSE: The purpose of this study is to evaluate the ability of cardio-ankle
      vascular index (CAVI), high-sensitivity C-reactive protein (hs-CRP) levels and
      homocysteine (Hcy) levels to screen for subclinical arteriosclerosis (subAs) in
      an apparently healthy population, with the view to obtaining an optimal
      diagnostic marker or profile for subAs. METHODS: Subjects (152) undergoing
      routine health examinations were recruited and divided into two groups: carotid
      arteriosclerosis (CA) and non-carotid arteriosclerosis (NCA), according to
      carotid intima-media thickness (CMIT). CAVI was calculated based on blood
      pressure and pulse wave velocity. Serum hs-CRP and Hcy levels were also measured.
      A Receiver Operating Characteristic (ROC) curve was plotted to evaluate the
      efficacy of each in carotid arteriosclerosis screening. Ten parameter
      combinations, designated W1 to W10, were compared in terms of sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV).
      RESULTS: The levels of all three parameters were significantly higher in the CA
      group, compared with the NCA group. ROC curves showed that the area under the
      curve (AUC) for CAVI was 0.708 (95%CI: 0.615-0.800), which is significantly
      larger than that of either hs-CRP (0.622) or Hcy (0.630), respectively (P <
      0.001). Maximum sensitivity (100%) and NPV (100%) were attained with W10, while
      maximum specificity (86.2%) and PPV (46.7%) were obtained with W7. With W9, the
      maximum Youden index (0.416) was obtained, with a sensitivity of 77.8% and
      specificity of 63.8%. CONCLUSIONS: CAVI is more effective than hs-CRP or Hcy for
      subAs screening. The optimal profile was obtained with a combination of CAVI and
      other parameters.

PMID- 23544610
TI  - HDAC inhibitor trichostatin A suppresses esophageal squamous cell carcinoma
      metastasis through HADC2 reduced MMP-2/9.
AB  - PURPOSE: The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has been
      shown to act as an anti-tumor agent; however, the effect and mechanism of TSA on
      the invasion of esophageal squamous cell carcinoma (ESCC) remains unknown.
      METHODS: To determine whether TSA suppresses the invasiveness of ESCC cell via
      HDAC2, the expression of HDAC2 in ESCC tissues and adjacent non-tumor tissues
      were compared using Western blot and immunohistochemistry. Cells were transfected
      with HDAC2 siRNAs and non-targeting control siRNA using Lipofectamine TM 2000.
      Cell invasion was investigated using a transwell assay. The protein levels of
      matrix metalloproteinase-2/9 (MMP-2/9) were examined by Western blot analysis.
      RESULTS: Expression of HDAC2 was significantly higher in ESCC than in adjacent
      non-tumor tissues. Additionally, the in vitro invasion assay found that both
      downregulation of HDAC2 expression and TSA treatment inhibited ESCC cell invasion
      by approximately 75%. Also, an MMP2/9-specific inhibitor sharply suppressed ESCC
      cell invasion. Furthermore, both downregulation of HDAC2 and treatment with TSA
      decreased MMP-2 and MMP-9 protein levels in ESCC cells. CONCLUSIONS: These
      results suggest that the inhibitory effect of TSA on cancer invasion is mediated
      through the suppression of HDAC2 expression, and that the reduction of MMP-2 and
      MMP-9 expression induced by HDAC2 may be involved in the anti-invasive effect of
      TSA.

PMID- 23544611
TI  - The protective effect of dexmedetomidine on bupivacaine-induced sciatic nerve
      inflammation is mediated by mast cells.
AB  - PURPOSE: This study was designed to assess the correlation between the
      neuroprotective effect of dexmedetomidine and oxidative stress, neural
      inflammation and mast cell stability in rats with bupivacaine-induced sciatic
      nerve toxicity. METHODS: Forty adult Wistar Albino rats, eight rats per group,
      were used. Saline (0.3 ml of 0.9%), dexmedetomidine (20 ug/kg), 0.5% bupivacaine
      or 0.5% bupivacaine+dexmedetomidine (20 ug/kg) was injected into the sciatic
      nerve. A control group of rats received no injection. Fourteen days after
      injection, the sciatic nerves were harvested and total oxidant status, total anti
      oxidant status, paraoxonase-1, galectin-3 and matrix metalloproteinase 2 and 9
      levels were measured in the sciatic nerves. In addition, the presence and status
      of inflammation, edema, and mast cells were evaluated histopathologically.
      RESULTS: The combination of dexmedetomidine and bupivacaine alleviated oxidative
      stress. In addition, it decreased matrix metalloproteinase 9 and galectin-3
      levels and increased matrix metalloproteinase 2 levels. Moreover, it stabilized
      recruited mast cells at the injury site; however, it did not significantly
      decrease inflammation or edema. CONCLUSION: Dexmedetomidine may ameliorate
      bupivacaine-induced neurotoxicity by modulating mast cell degranulation. The
      neuroprotective effect of dexmedetomidine may make it a suitable adjuvant agent
      to local anesthetics in peripheral nerve blocks.

PMID- 23544613
TI  - Enzyme-catalyzed synthesis of aliphatic-aromatic oligoamides.
AB  - Enzymatically catalyzed polycondensation of p-xylylenediamine and diethyl
      sebacate resulted in oligo(p-xylylene sebacamide) with high melting temperatures
      (223-230  degrees C) and the enzymatic polycondensation of dimethyl terephthalate
      and 1,8-diaminooctane leads to oligo(octamethylene terephthalamide) with two
      melting temperatures at 186 and 218  degrees C. No oligoamides, but products 1
      and 2, were formed from the enzymatic reaction of dimethyl terephthalate and p
      xylylenediamine. All reactions were catalyzed by CAL-B, icutinase, or CLEA
      cutinase. All reactions catalyzed by CAL-B show higher conversion than reactions
      catalyzed by icutinase or CLEA cutinase. The highest DPmax of 15 was achieved in
      a one-step and two-step synthesis of oligo(p-xylylene sebacamide) catalyzed by
      CLEA cutinase.

PMID- 23544614
TI  - Colorimetric and fluorometric assays based on conjugated polydiacetylene
      supramolecules for screening acetylcholinesterase and its inhibitors.
AB  - Polydiacetylene supramolecules (PDAs) are unique sensing materials. Upon
      environmental stimulation, blue PDAs can undergo a colorimetric transition from
      blue to red accompanied by fluorescence enhancement. In this paper, we report a
      new PDA system polymerized from a mixed liposome comprising 2-(2-(2
      hydroxyethoxy)ethoxy)ethyl pentacosa-10,12-diynoate and pentacosa-10,12-diynoic
      acid at a 3:7 ratio. The PDA system provided new colorimetric and fluorometric
      assay methods for screening acetylcholinesterase and its inhibitors through three
      processes. First, myristoylcholine reacted with PDAs, which then underwent
      colorimetric and fluorometric transition. Second, acetylcholinesterase catalyzed
      the hydrolysis of myristoylcholine into tetradecanoic acid, which reduced the
      myristoylcholine concentration and led to faded color and fluorescence. Third and
      last, acetylcholinesterase inhibitors retarded the activity of
      acetylcholinesterase, thereby inducing the recovery of color and fluorescence.

PMID- 23544615
TI  - Impurity partitioning during colloidal crystallization.
AB  - We have found that an impurity partitioning takes place during growth of
      colloidal crystals, which was recognized by the fact that the impurity
      concentration in the solid (CS) was different from that in the initial solution
      (C0). The effective partition coefficient k(eff) (=CS/C0) was investigated for
      pure polystyrene and polystyrene dyed with fluorescent particles by changing the
      ratio of particle diameters d(imp)/d(cryst) and growth rate V. At each size ratio
      for the polystyrene impurity, k(eff) was less than unity and increased to unity
      with increasing V, whereas at a given growth rate, k(eff) increased to unity as
      d(imp)/d(cryst) approached unity. These results were consistent with the solute
      behavior analyzed using the Burton, Prim, and Slichter (BPS) model. The obtained
      k0, equilibrium partition coefficient, from a BPS plot increased as
      d(imp)/d(cryst) approached unity. In contrast, while the fluorescent particles
      also followed the BPS model, they showed higher k0 values than those of the same
      size of polystyrene particles. A k0 value greater than unity was obtained for
      impurities that were similar in size to the host particle. This behavior is
      attributed to the positive free energy of fusion associated with the
      incorporation of the fluorescent particles into the host matrix. Such positive
      free energy of fusion implies the presence of the enthalpy associated with
      interaction between particles.

PMID- 23544616
TI  - COI barcodes and phylogeny of doves (Columbidae family).
AB  - Cytochrome oxidase subunit I (COI) gene has been recognized as an authentic tool
      for species identification. Besides its potential barcoding capacity, COI
      sequences have also been used for inferring the phylogeny. Phylogenetic
      relationships among genera of Columbidae (pigeons and doves family) have not been
      fully resolved because of scarce sampling of taxa and limited availability of
      sequence data. In this study, we have evaluated the efficiency of COI barcodes
      for species identification and phylogenetic analysis of various doves. We
      sequenced the 693 bp region of COI gene of three species of doves including Oena
      capensis, Streptopelia decaocto, and Streptopelia senegalensis. After retrieving
      the relevant sequences from the GenBank, the entire data-set of 85 sequences
      represented 25 dove species from 11 different genera of the family Columbidae.
      The COI sequences of four species including Chalcophaps indica (two specimens),
      Columbina inca (five specimens), Geopelia striata (three specimens), and
      Macropygia phasianella (three specimens) were identical. The mean intraspecific
      base differences ranged from 0 to 37 while the P-distances ranged between 0 and
      0.058. For most of the species, the P-distances were <= 0.008. Phylogenetic
      analysis differentiated the taxa into three major clusters. One of the clusters
      grouped five genera including Claravis, Columbina, Gallicolumba, Geopelia, and
      Geotrygon. The remaining two clusters grouped three genera each including
      Chalcophaps, Oena, and Turtur in one cluster and Macropygia, Streptopelia, and
      Zenaida in another cluster. Further sub-clustering clearly separated all the
      genera into individual clusters except two discrepancies for the genera
      Streptopelia and Turtur. Species-level cladistics clearly separated all the
      species into distinctive clades. In conclusion, COI barcoding is a powerful tool
      for species identification with added information on phylogenetic inference. The
      finding of this study will help to understand the complex phylogeny of the family
      Columbidae.

PMID- 23544619
TI  - Life cycle responses of the midge Chironomus riparius to compounds with different
      modes of action.
AB  - Compounds with different modes of action may affect life cycles of biota
      differently. The aim of the present study was therefore to investigate the impact
      of four chemicals with different modes of action, including the essential metal
      copper, the nonessential metal cadmium, the organometal tributyltin, and the
      polycyclic aromatic compound phenanthrene, on chronic lethal and sublethal life
      cycle effect parameters of the nonbiting midge Chironomus riparius, applying a 28
      day sediment toxicity test. Tributyltin and cadmium delayed emergence
      significantly over a wide range of sublethal concentrations, while this range was
      narrow for copper and almost absent for phenanthrene. The chronic LC50/LOECEmT50
      ratio, expressing these differences, amounted to 1.5, 3.5, 12.0, and 18.2 for
      respectively phenanthrene, copper, cadmium, and tributyltin. Thus the more
      specific the compounds mode of action, the higher the chronic LC50/LOECEmT50
      ratio, as previously observed for acute-to-chronic ratios (ACRs). Comparison of
      our results with literature derived LC50/LOEC ratios showed a comparable trend
      and a lower variability compared to ACRs. We therefore conclude that the
      presently proposed chronic ratio is indicative for the specificity of a chemicals
      mode of action and that it is less variable than the ACR.

PMID- 23544620
TI  - Inducing rapid cellular response on RGD-binding threaded macromolecular surfaces.
AB  - The rapid response of integrin beta1 molecules to an RGD peptide on a dynamic
      polyrotaxane surface was successfully induced. As a result, RGD peptides
      introduced on a highly dynamic cyclodextrin molecule enhanced the frequency of
      contact with specific integrin molecules on the cell membrane at the early stage
      of material-cell interactions.

PMID- 23544621
TI  - Low-level shear stress induces human mesenchymal stem cell migration through the
      SDF-1/CXCR4 axis via MAPK signaling pathways.
AB  - Mesenchymal stem cells (MSCs) are able to home and migrate into damaged tissues
      and are thus, considered an optimal therapeutic strategy for clinical use. We
      previously demonstrated that higher shear stress (>2 Pa) hindered human MSC
      (hMSC) migration, whereas lower shear stress (0.2 Pa) induced cell migration
      through mitogen-activated protein kinase (MAPK) pathways. Here the mechanisms
      underlying shear stress-induced hMSC migration have been studied further. An MSC
      monolayer was mechanically wounded and subsequently exposed to low-level shear
      stress of 0.2 Pa. Image analysis was performed to quantify cell migration speeds
      under both flow and static conditions. hMSCs along both upstream- and downstream
      edges of the wound migrated at a similar speed to cover the wounded area under
      static conditions, whereas shear stress induced cells along the downstream edge
      of the wound to migrate significantly faster than those along the upstream edge.
      We also found that shear stress upregulated the secretion of stromal-derived
      factor-1 (SDF-1), which stimulated its receptor CXCR4 expression in hMSCs until
      the cells covered the wounded area. A CXCR4 antagonist repressed both cell
      migration and activation of c-Jun N-terminal kinase (JNK) and p38 MAPK but did
      not affect extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation.
      When MAPK activation in upstream- and downstream hMSCs was evaluated separately,
      ERK1/2 was activated earlier in downstream than in upstream cells. These results
      indicate that the SDF-1/CXCR4 axis mediates shear stress-induced hMSC migration
      through JNK and p38 MAPK pathways and that the difference in migration speeds
      between upstream- and downstream cells may be due to ERK1/2 activation. 

PMID- 23544622
TI  - Metformin overdose-induced hypoglycemia in the absence of other antidiabetic
      drugs.
AB  - CONTEXT: Lactic acidosis is a well-recognized consequence of metformin.
      Hypoglycemia has been reported previously in metformin overdose, but the presence
      of other co-ingestions (e.g., a sulfonylurea) was not definitively excluded. CASE
      DETAILS: A 15-year-old girl ingested 75 g of metformin and 3 g of quetiapine. On
      examination in the emergency department 2 h later, she was drowsy but had normal
      vital signs. She developed lactic acidosis, hypotension, and recurrent and severe
      hypoglycemia (15 mg/dL and 20 mg/dL), requiring boluses of 50%dextrose. The first
      episode of hypoglycemia occurred approximately 4 h after ingestion. Serum
      metformin level 2 h after ingestion was 267 mg/L (therapeutic range, 0.465-2.5),
      and serum insulin was 2 mU/L (normal range, 6-35). Extensive laboratory
      investigation using high-resolution mass-spectrometry ruled out other possible
      hypoglycemic agents. She recovered after hemodialysis. DISCUSSION: Metformin
      overdose can cause severe hypoglycemia in the absence of other antidiabetic
      drugs. Potential mechanisms of metformin-induced hypoglycemia include decreased
      hepatic glucose production, decreased glucose absorption, and poor oral intake.

PMID- 23544623
TI  - Detection of iron ligands in seawater and marine cyanobacteria cultures by high
      performance liquid chromatography-inductively coupled plasma-mass spectrometry.
AB  - Organic ligands dominate the speciation of iron in the ocean. Little is known,
      however, about the chemical composition and distribution of these compounds.
      Here, we describe a method to detect low concentrations of organic Fe ligands
      using reverse-phase high-performance liquid chromatography (HPLC) tandem
      multicollector inductively coupled plasma mass spectrometry. This technique can
      be used to screen seawater and marine cultures for target compounds that can be
      isolated and structurally characterized. Sensitive detection (<1 picomole Fe) is
      achieved using an iron-free HPLC system to reduce background Fe levels,
      minimizing (40)Ar(16)O(+) interferences on (56)Fe with a hexapole collision cell,
      and introducing oxygen into the sample carrier gas to prevent the formation of
      reduced carbon deposits that decrease sensitivity. This method was tested with a
      chromatographic separation of five trace metal complexes that represent the
      polarity range likely found in seawater. Good separation was achieved with a 20
      min water/methanol gradient, although sensitivity decreased by a factor of 2 at
      high organic solvent concentrations. Finally, Fe ligand complexes were detected
      from the organic extract of surface South Pacific seawater and from culture media
      of the siderophore producing cyanobacteria Synechococcus sp. PCC 7002. 

PMID- 23544624
TI  - Variation in family physicians' recording of auscultation abnormalities in
      patients with acute cough is not explained by case mix. A study from 12 European
      networks.
AB  - BACKGROUND: Conflicting data on the diagnostic and prognostic value of
      auscultation abnormalities may be partly explained by inconsistent use of
      terminology. OBJECTIVES: To describe general practitioners use of chest
      auscultation abnormality terms for patients presenting with acute cough across
      Europe, and to explore the influence of geographic location and case mix on use
      of these terms. METHODS: Clinicians recorded whether 'diminished vesicular
      breathing', 'wheezes', 'crackles' and 'rhonchi' were present in an observational
      study of adults with acute cough in 13 networks in 12 European countries. We
      describe the use of these terms overall and by network, and used multilevel
      logistic regression to explore variation by network, controlling for patients'
      gender, age, comorbidities, smoking status and symptoms. RESULTS: 2345 patients
      were included. Wheeze was the auscultation abnormality most frequently recorded
      (20.6% overall) with wide variation by network (range: 8.3-30.8%). There was
      similar variation for other auscultation abnormalities. After controlling for
      patient characteristics, network was a significant predictor of auscultation
      abnormalities with odds ratios for location effects ranging from 0.37 to 4.46 for
      any recorded auscultation abnormality, and from 0.25 to 3.14 for rhonchi.
      CONCLUSION: There is important variation in recording chest auscultation
      abnormalities by general practitioners across Europe, which cannot be explained
      by differences in patient characteristics. There is a need and opportunity for
      standardization in the detection and classification of lung sounds.

PMID- 23544625
TI  - Chitosan(PEO)/silica hybrid nanofibers as a potential biomaterial for bone
      regeneration.
AB  - New hybrid nanofibers prepared with chitosan (CTS), containing a total amount of
      polyethylene oxide (PEO) down to 3.6wt.%, and silica precursors were produced by
      electrospinning. The solution of modified sol-gel particles contained
      tetraethoxysilane (TEOS) and the organosilane 3-glycidyloxypropyltriethoxysilane
      (GPTEOS). This is rending stable solution toward gelation and contributing in
      covalent bonding with chitosan. The fibers encompass advantages of biocompatible
      polymer template silicate components to form self-assembled core-shell structure
      of the polymer CTS/PEO encapsulated by the silica. Potential applicability of
      this hybrid material to bone tissue engineering was studied examining its
      cellular compatibility and bioactivity. The nanofiber matrices were proved
      cytocompatible when seeded with bone-forming 7F2-cells, promoting attachment and
      proliferation over 7 days. These found to enhance a fast apatite formation by
      incorporation of Ca(2+) ions and subsequent immersion in modified simulated body
      fluid (m-SBF). The tunable properties of these hybrid nanofibers can find
      applications as active biomaterials in bone repair and regeneration.

PMID- 23544626
TI  - Effects of anionic structure on the dissolution of cellulose in ionic liquids
      revealed by molecular simulation.
AB  - Although ionic liquids (ILs) have shown promise in the pretreatment of cellulose
      and lignocellulosic biomass, there is no established rule to guide the rational
      design of such ILs up to date. In this work, the mixtures of cellulose with a
      series of ILs having the same cation [C2mim](+) but different anions have been
      simulated to study the effect of anionic nature on the dissolution of cellulose.
      It was shown that hydrogen bonds (HBs) were formed between anions of the ILs and
      hydroxyl protons of cellulose. Cl(-) anion and O atom of [CH3COO](-) and
      [(CH3O)2PO2](-) are better HB acceptors. Furthermore, the effects of
      electronegativity of HB acceptor atoms, steric effect of alkyl chain length and
      electron-withdrawing group of the anions on their HB acceptor ability have been
      investigated. The obtained results are expected to be important for the rational
      design of novel ILs for efficient dissolution of cellulose.

PMID- 23544627
TI  - Extraction and chemical characterization of Angelica sinensis polysaccharides and
      its antioxidant activity.
AB  - In the present study, the Angelica sinensis polysaccharides (ASP) extraction
      procedure was optimized by an L9 (3(4)) orthogonal array experimental design
      (OAD) with four factors at three levels. Under the optimal extraction condition
      (extraction time 180 min, ratio of water to solid 6, extraction temperature 100
      degrees C, and extraction number 4), extraction yield of ASP was 5.6%. Rabbits
      were fed for 40 days with A. sinensis polysaccharides at a dose of 150 or 300
      mg/kg body weight, respectively. At the end of 40 days, animals received cerebral
      ischemia reperfusion operation. CT perfusion imaging (CTP) analysis showed that
      rCBF and rCBV were significantly increased, whereas rMTT and rTTP were decreased
      in the ischemia cerebral tissue compared to CIR group rabbits. ASP significantly
      decreased oxidative damage, and increased antioxidant enzymes activities in
      brains of CIR animals. Moreover, ASP significantly enhanced the Ach, Na(+),K(+)
      ATPase, Ca(2+),Mg2(+)-ATPase and glucose levels, decreased AChE activity in brain
      tissue of the experimental animals. These results suggest a potent role of ASP in
      protection of brain oxidative injury in CIR animals.

PMID- 23544628
TI  - Influence of sericin/TiO2 nanocomposite on cotton fabric: part 1. Enhanced
      antibacterial effect.
AB  - Sericin as a biological material was extracted from raw silk by boiling in hot
      water and nano-TiO2 was dispersed in its solution. The prepared finishing agents
      with and without polycarboxylic acid cross-linking agents were treated on cotton
      fabric using pad-dry-cure. Presence of sericin, nano-TiO2, and cross-linking
      agents on cotton fabric was confirmed by at least one of the following
      experimental FTIR, SEM, EDX, and XRD. The antibacterial activity and the
      durability of modified cotton fabrics were investigated against one Gram-positive
      bacterium (Staphylococcus aureus) and one Gram-negative bacterium (Escherichia
      coli). The finishing treatment on the cotton fabric was more effective against S.
      aureus than E. coli. The fabrics treated with nano-TiO2 were possessed more
      activity against bacteria as compared to sericin and also considerably improved
      with given nanocomposite. The antibacterial activity of treated fabrics with
      cross-linking agents has not been considerably changed after 20 and 40
      launderings. The fabrics treated with given nanocomposites did not dramatically
      affect the breaking strength.

PMID- 23544629
TI  - Structure and properties of cellulose/poly(N-isopropylacrylamide) hydrogels
      prepared by SIPN strategy.
AB  - Semi-interpenetrating polymer network (SIPN) strategy was employed to fabricate a
      kind of novel hydrogels composed of cellulose and poly(N-isopropylacrylamide)
      (PNIPAAm) in the presence of N,N'-methylenebisacrylamide (MBAAm) as the
      crosslinker and benzoyl peroxide (BPO) as the initiator. The results from FTIR
      and TGA indicated that the network indeed existed in the SIPN hydrogels. The data
      from experiments, those related to the swelling behavior of the hydrogels at
      different temperatures in particular, demonstrated the thermal sensitivity of
      these hydrogels. The impact of crosslinker content on the hydrogel properties was
      discussed as well. The swelling ratio of hydrogels decreased with increasing the
      content of MBAAm. Besides, the loading and releasing behavior of the hydrogels
      were examined using dimethyl methylene blue as a model drug. These novel
      hydrogels combining the advantages of natural polymer with thermal responsive
      behavior are of great potential to be applied to drug delivery and control
      release systems.

PMID- 23544630
TI  - Amphiphilic polymers bearing gluconolactone moieties: synthesis and long side
      chain crystalline behavior.
AB  - The synthesis and characterization of amphiphilic polymers bearing gluconolactone
      moieties has been described. In a first step, an unprotected glycomonomer 2-[({[4
      (d-gluconamid-N-yl)butyl]amino}carbonyl)oxy]ethyl acrylate, HEAG, has been
      synthesized. Posterior, this glycomonomer has been copolymerized with methyl
      methacrylate at different compositions and the kinetic behavior has been also
      studied calculating the monomer reactivity ratios by Kelen-Tudos extended
      equation. In addition, the long side-chain crystalline behavior of these
      carbohydrate-based copolymers with high composition of glycomonomer has been
      examined by using conventional and modulated differential scanning calorimetry
      and X-ray diffraction measurements. At the same time, the phase separation
      behavior of carbohydrate-based copolymers with lower HEAG content has been
      determined by their glass transition temperature measurements. Finally, the
      thermal stability of all these amphiphilic copolymers has been evaluated by
      thermogravimetric analysis.

PMID- 23544631
TI  - Influence of citric acid and curing on moisture sorption, diffusion and
      permeability of starch films.
AB  - Starch films with different amounts of citric acid produced by solution casting
      were subjected to different curing temperatures and compared with films
      plasticized with glycerol. The films were tested in a controlled moisture
      generator, which enabled the moisture sorption to be measured and the diffusion
      coefficient and water vapor permeability to be calculated. It was shown that
      increasing the amount of citric acid added led to a reduction in the equilibrium
      moisture content, diffusion coefficient and water vapor permeability of the
      films, the values of which were all considerably lower than the values obtained
      for the films plasticized by glycerol. It was also seen that curing the film with
      30 pph citric acid at 150 degrees C led to a significant reduction in the
      equilibrium moisture content, the diffusion coefficient and the water vapor
      permeability at high relative humidity which suggests that crosslinking occurred.
      The calculated water vapor permeability data were comparable with the value
      obtained with direct measurements.

PMID- 23544632
TI  - Characterization of cellulose II nanoparticles regenerated from 1-butyl-3
      methylimidazolium chloride.
AB  - Regenerated cellulose nanoparticles (RCNs) including both elongated fiber and
      spherical structures were prepared from microcrystalline cellulose (MCC) and
      cotton using 1-butyl-3-methylimidazolium chloride followed by high-pressure
      homogenization. The crystalline structure of RCNs was cellulose II in contrast to
      the cellulose I form of the starting materials. Also, the RCNs have decreased
      crystallinity and crystallite size. The elongated RCNs produced from cotton and
      MCC had average lengths of 123 +/- 34 and 112 +/- 42 nm, and mean widths of 12 +/
      5 and 12 +/- 3 nm, respectively. The average diameter of spherical RCNs from MCC
      was 118 +/- 32nm. The dimensions of the various RCNs were all well fitted with an
      asymmetrical log-normal distribution function. The RCN has a two-step pyrolysis,
      different from raw MCC and cotton that have a one-step process.

PMID- 23544633
TI  - Suspensions of vacuum-freeze dried starch nanoparticles: influence of NaCl on
      their rheological properties.
AB  - The effect of addition of NaCl on rheological properties of suspensions
      containing vacuum freeze dried starch nanoparticles was studied. These starch
      nanoparticles were produced through high pressure homogenization and emulsion
      cross-linking technique. Rheological properties such as continuous shear
      viscosity, storage and loss moduli and creep-recovery were measured. The presence
      of NaCl at concentration (5-15%, w/v) increased viscosity marginally (p>0.05)
      while at 20% (w/v) it significantly (p<0.05) increased viscosity. The presence of
      NaCl enhanced heat stability and weakened gelling capacity of suspensions. NaCl
      concentration below 15% (w/v) marginally (p>0.05) increased the storage and loss
      moduli of suspensions. At 20% (w/v), NaCl increased both moduli significantly
      (p<0.05) within frequency range tested (0.1-10 rad/s). Creep-recovery behavior
      was affected by NaCl and recovery rate was the highest (98.6%) at 20% (w/v) NaCl.
      The Cross, Power Law and Burgers' models followed experimental shear viscosity,
      storage and loss moduli and creep-recovery data reasonably well (R(2)>0.94).

PMID- 23544634
TI  - Profiling of soluble neutral oligosaccharides from treated biomass using solid
      phase extraction and LC-TOF MS.
AB  - Thermochemical pretreatments of cellulosic biomass are known to improve cell wall
      enzymatic digestibility, while simultaneously releasing substantial amounts of
      soluble oligosaccharides. Profiling of oligosaccharides released during
      pretreatment yields information essential for choosing glycosyl hydrolases
      necessary for cost-effective conversion of cellulosic biomass to desired
      biofuel/biochemical end-products. In this report we present a methodology for
      profiling of soluble neutral oligosaccharides released from ammonia fiber
      expansion (AFEXTM)-pretreated corn stover. Our methodology employs solid phase
      extraction (SPE) enrichment of oligosaccharides using porous graphitized carbon
      (PGC), followed by high performance liquid chromatography (HPLC) separation using
      a polymeric amine based column and electrospray ionization time-of-flight mass
      spectrometry (ESI-TOF-MS). For structural elucidation on the chromatographic time
      scale, nonselective multiplexed collision-induced dissociation was performed for
      quasi-simultaneous acquisition of oligosaccharide molecular and fragment masses
      in a single analysis. These analyses revealed glucans up to degree of
      polymerization (DP) 22 without modifications. Additionally, arabinoxylans up to
      DP=6 were detected in pretreated biomass extracts (post-enzymatic digestion).
      Cross-ring fragment ion abundances were consistent with assignment of linkages
      between sugar units in glucans and also xylose backbone in arabinoxylans as 1-4
      linkages. Comprehensive profiling of soluble oligosaccharides also demonstrated
      decreases in levels of acetate esters of arabinoxylan oligosaccharides with
      concomitant increases in nonacetylated oligosaccharides that were consistent with
      earlier observations of 85% release of acetate esters by AFEXTM pretreatment.

PMID- 23544635
TI  - Effect of lubricant on mechanical and rheological properties of compatibilized
      PP/sawdust composites.
AB  - An investigation was performed regarding the effect of compatibilizer and
      lubricant concentrations on the mechanical and rheological properties of
      polypropylene/sawdust composites using two-level factorial central composite
      design. Maleic anhydride grafted PP (PP-g-MA) was used as compatibilizer and the
      lubricant used was Struktol TPW 113. Composites without these additives were also
      prepared. Processing was carried out in a co-rotating twin-screw extruder coupled
      to a Haake rheometer. Mechanical properties were assessed from tensile tests and
      rheological properties were evaluated by oscillatory measurements and melt flow
      index (MFI) test. Tensile strength improved with increasing compatibilizer
      concentration in the composites and reached a maximum value in the absence of
      lubricant. When both additives were present tensile strength decreased,
      suggesting a possible interaction between lubricant and compatibilizer, reducing
      efficiency of the latter. The general trend observed for rheological results was
      a decrease in complex viscosity, storage modulus and MFI when both additives were
      present.

PMID- 23544636
TI  - Efficient enzymatic hydrolysis of the bagasse pulp prepared with active oxygen
      and MgO-based solid alkali.
AB  - The enzymatic hydrolysis of the bagasse pulp prepared from the treatment process
      with active oxygen and MgO-based solid alkali was studied. The hydrolysates were
      tested by IC (ionic chromatography) for the analysis of monosaccharide.
      Additionally, the changes of pulp before and after hydrolysis were characterized
      with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy
      (SEM), X-ray diffraction (XRD), Kajaani cellulose automatic analyzer and atomic
      force microscopy (AFM) techniques. The results showed that an optimized sugar
      yield of 82.38% was obtained at the substrate concentration of 5% for 72h with
      the enzyme dosage of 15IU/g. Furthermore, as the length of the cellulose fiber
      decreased, the crystallinity of cellulose increased, and more depressions
      appeared on the surface of pulp after enzymatic hydrolysis.

PMID- 23544637
TI  - Locust bean gum: a versatile biopolymer.
AB  - Biopolymers or natural polymers are an attractive class of biodegradable polymers
      since they are derived from natural sources, easily available, relatively cheap
      and can be modified by suitable reagent. Locust bean gum is one of them that have
      a wide potentiality in drug formulations due to its extensive application as food
      additive and its recognized lack of toxicity. It can be tailored to suit its
      demands of applicants in both the pharmaceutical and biomedical areas. Locust
      bean gum has a wide application either in the field of novel drug delivery system
      as rate controlling excipients or in tissue engineering as scaffold formation.
      Through keen references of reported literature on locust bean gum, in this
      review, we have described critical aspects of locust bean gum, its manufacturing
      process, physicochemical properties and applications in various drug delivery
      systems.

PMID- 23544638
TI  - Structure and properties of poly (lactic acid)/Sterculia urens uniaxial fabric
      biocomposites.
AB  - Uniaxial cellulose fabric Sterculia urens reinforced poly (lactic acid) (PLA)
      matrix biocomposites were prepared by a two-roll mill. In order to assess the
      suitability of Sterculia fabric as reinforcement for PLA matrix, the
      PLA/Sterculia fabric biocomposites were prepared. Tensile parameters, such as
      maximum stress, Young's modulus and elongation-at-break, were determined using
      the Universal Testing Machine. The effect of alkali treatment and silane-coupling
      agent on the tensile properties of PLA-based biocomposites was studied. The
      results of thermogravimetric analysis show that uniaxial treatment of the fabric
      can improve the degradation temperature of the biocomposites. Moreover,
      morphological studies by scanning electron microscopy confirmed that better
      adhesion between the uniaxial fabric and the matrix was achieved. It was
      established that standard PLA resins are suitable for the manufacture of S. urens
      uniaxial fabric reinforced biocomposites with excellent engineering properties,
      useful for food packaging.

PMID- 23544639
TI  - Polysaccharide of Hohenbuehelia serotina as a defense against damage by whole
      body gamma irradiation of mice.
AB  - This study was designed to investigate the antioxidant, immunomodulation and
      radioprotective activities of the polysaccharides from Hohenbuehelia serotina
      (HSP) against the damages induced by (60)Co-radiation in vivo. Antioxidant
      results showed that the mice treated with HSP could effectively increase the
      superoxide dismutase (SOD) and catalase (CAT) activities, and reduce the
      malondialdehyde (MDA) level after 6Gy irradiation compared to irradiated, non
      treated controls. Administration with HSP (200mg/kg BW) significantly promote the
      proliferation of splenocytes (p<0.01), and prevent the number of the blood WBC
      decrease and the function of hematopoietic decline which caused by irradiation in
      whole blood. HSP displayed strong immunomodulation activity in vivo, and the
      effect was further verified by the assay of monocyte phagocytosis. In addition,
      HSP significantly inhibit irradiation-induced spleen cells arrest into G0/G1
      phase. These results suggested that HSP exerts an effective protection against
      radiation-induced injury by improving the antioxidant and immunomodulation
      activities.

PMID- 23544640
TI  - Biodegradable chitosan nanogels crosslinked with genipin.
AB  - Chitosan nanoparticles crosslinked with genipin were prepared by reverse
      microemulsion that allowed to obtain highly monodisperse (3-20 nm by TEM)
      nanogels. The incorporation of genipin into chitosan was confirmed and
      quantitatively evaluated by UV-vis and (1)H NMR. Loosely crosslinked chitosan
      networks showed higher water solubility at neutral pHs than pure chitosan. The
      hydrodynamic diameter of the genipin-chitosan nanogels ranged from 270 to 390 nm
      and no remarkable differences were found when the crosslinking degree was varied.
      The hydrodynamic diameters of the nanoparticles increased slightly at acidic pH
      and the protonation of ionizable amino groups with the pH was confirmed by the
      zeta potential measurements. The biocompatible and biodegradable nature, as well
      as the colloidal and monodisperse particle size of the prepared nanogels, make
      them attractive candidates for a large variety of biomedical applications.

PMID- 23544641
TI  - Polymorphic transformation of cellulose I to cellulose II by alkali pretreatment
      and urea as an additive.
AB  - The effect on crystalline structure transformation from cellulose I to cellulose
      II polymorph was studied of the cotton linter treated with NaOH with and without
      urea as an additive, analyzed by wide-angle X-ray diffraction analysis. Cotton
      linter treated with increasing NaOH concentration showed at 15 wt% sudden
      transformation from cellulose I to cellulose II polymorph. But when urea 5 wt%
      was used as additive along with 15 wt% NaOH concentration the magnitude of the
      transformation reduced largely. The crystallinity index showed a gradual decrease
      with increasing concentration of NaOH. The crystallinity index showed a gradual
      decrease with increasing concentration of NaOH with or without addition of urea,
      nevertheless with addition of urea a further slight more transformation was also
      observed.

PMID- 23544642
TI  - Doxorubicin loading fucoidan acetate nanoparticles for immune and chemotherapy in
      cancer treatment.
AB  - In order to develop immuno- and chemotherapy agents, self-organized acetylated
      fucoidan (AcFu) nanoparticles were designed. Doxorubicin (DOX), used as a model
      drug, was loaded into the AcFu nanoparticles by dialysis. The DOX loading
      efficacy and content were 71.1% and 3.6%, respectively. Approximately 140 nm of
      spherical nanoparticles were obtained. DOX-loaded AcFu nanoparticles (DOX-AcFu)
      exhibited first-order drug release behavior for 5 days. Interestingly, AcFu
      treated Raw264.7 macrophages overexpressed various anti-tumor cytokines, such as
      tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony
      stimulating factor (GM-CSF). The ability of DOX-AcFu to suppress drug efflux was
      revealed by confocal microscope images and FACS analysis in multidrug resistance
      (MDR) cells. IC50 (50% inhibitory concentration) value of DOX-AcFu was lower than
      that of free DOX in the MDR model cells. Based on these results, we strongly
      suggest that AcFu nanoparticles have a promising potential for development as a
      one-step therapy containing agents for both immuno- and chemotherapy.

PMID- 23544643
TI  - Characterization and lectin microarray of an immunomodulatory heteroglucan from
      Pleurotus ostreatus mycelia.
AB  - Glucans isolated from various mushroom and mycelia sources are interestingly
      being studied nowadays as a potent therapeutic agent. The present work was
      focused on the isolation, characterization and immunomodulatory study of a novel
      water soluble glucan from the pure mycelia of Pleurotus ostreatus. The extracted
      glucan was found to have a high molecular weight of ~2.7 * 10(6)Da and mainly
      comprised of glucose, mannose and fucose in a ratio of 3:2:1 with both beta and
      alpha linkages. Presence of terminal or interior glucose, mannose and fucose
      residues was also revealed using a high throughput miniaturized platform of
      lectin microarray. The heteroglucan folded into a triple helical conformation and
      exhibited enhanced immune cell activation and anti-tumor potential in tumor
      bearing mice model. Thus, potential biological functions incorporated in these
      glucan molecules acts in accord with its structural property and exploration of
      such structure-function relationship will unveil its diverse mechanism of action.

PMID- 23544644
TI  - Properties of the modified cellulosic fabrics using polyurethane acrylate
      copolymers.
AB  - Polyurethane acrylate copolymers (PAC) were synthesized via emulsion
      polymerization following three step synthesis process using toluene-2,4
      diisocyanate, hydroxy terminated poly(caprolactone) diol, 2-hydroxyethylacrylate
      (HEA) and butyl acrylate (BuA). Structural characteristics of the synthesized
      polyurethane acrylate copolymer (PAC) were studied using Fourier Transform
      Infrared (FT-IR) spectrophotometer and are with accordance with the proposed PAC
      structure. The physicochemical properties such as solid contents (%), tackiness,
      film appearance and emulsion stability were studied, discussed and co-related
      with other findings. The plain weave poly-cotton printed fabrics after
      application of PAC was evaluated applying colorfastness standard test method. The
      results revealed that emulsion stability is the main controlling factor of the
      synthesized material in order to get better applications and properties. The
      emulsion stability of the synthesized material increased with increase in
      molecular weight of the polycaprolactone diol.

PMID- 23544645
TI  - Plasticization effect of triacetin on structure and properties of starch ester
      film.
AB  - The aim of this work was to evaluate the plasticizing effect of triacetin on the
      structure and properties of starch ester film and further establish the structure
      property relationships. The presence of triacetin resulted in multiple structure
      changes of the film. The mobility of macromolecular chain was increased to form
      scattered crystallite during the film formation process. The amorphous region was
      enlarged to contain more triacetin squeezed from crystalline region. The
      plasticization of triacetin and restriction of crystallite oppositely influenced
      the mobility of macromolecular chains in different regions. The thermal stability
      of triacetin changed along with its fluctuant interaction with macromolecules.
      Comparatively, the enhanced ether bond and the restriction from crystalline
      regions on the mobility of the amorphous chain consequently improved the thermal
      stability of the film matrix. The interaction between triacetin and starch ester
      was essential to film forming but unexpectedly lowered the triacetin stability.

PMID- 23544646
TI  - Extracellular polymeric substances from two biofilm forming Vibrio species:
      characterization and applications.
AB  - The early biofilm colonizing Vibrio campbellii and Vibrio fortis produced 400 and
      134 mg L(-1) extracellular polymeric substances (EPS), respectively of distinct
      composition in planktonic cultures. The EPS of V. campbellii consisted of five
      monosaccharides: arabinose, galactose, glucose, mannose and rhamnose, however,
      that of V. fortis has only three monosaccharides: arabinose, galactose and
      mannose. The AFM topography analysis showed different morphology and physical
      characteristics of EPSs. FTIR and NMR spectral analyses revealed characteristic
      functional groups of the polysaccharides. EPSs were amorphous in nature and
      contained characteristic diffraction peaks. EPSs showed high emulsifying activity
      and pseudoplastic rheology. This is the first report of detailed characterization
      of EPS produced by V. campbellii and V. fortis, so far. Detailed analytical (FT
      IR, (1)H NMR, PXRD, etc.) and bio-physicochemical characteristics
      (thermostability, emulsifying and rheological properties) of EPSs showed
      potential for industrial applications.

PMID- 23544647
TI  - Phosphorylated curdlan microgels. Preparation, characterization, and in vitro
      drug release studies.
AB  - Curdlan derivative with anionic phosphate groups was used for the first time to
      obtain hydrogel microspheres. The chemical cross-linking of the phosphorylated
      curdlan was performed with epichlorohydrin using the water-in-oil inverse
      emulsion technique. The optical and scanning electron microscopies were used to
      analyze the morphology of the microgels, whereas the FTIR spectroscopy was used
      to investigate their chemical structure. The main characteristics such as the
      swelling degree, the exchange capacity, and the thermal resistance were also
      studied. These new anionic microgels could be used as potential carriers for
      controlled release of opposite charged drugs retained through electrostatic
      forces. Diphenhydramine, a cationic model drug, was used to investigate the
      loading and the release processes in various pH media simulating physiological
      fluids. Several mathematical models were applied to evaluate the drug transport
      processes and to calculate the drug diffusion coefficients. The synthesized
      microspheres presented an excellent biocompatibility.

PMID- 23544648
TI  - Sulfation and biological activities of konjac glucomannan.
AB  - The sulfation of konjac glucomannan and its anti-HIV and blood anticoagulant
      activities were investigated. Konjac glucomannan is a polysaccharide occurring
      naturally in konjac plant tubers and has high molecular weights. Solubility in
      water is very low, and the aqueous solutions at low concentrations have high
      viscosity. Before sulfation, hydrolysis by diluted sulfuric acid was carried out
      to decrease the molecular weights of M-n=19.2 * 10(4)-0.2 * 10(4). Sulfation with
      piperidine-N-sulfonic acid or SO3-pyridine complex gave sulfated konjac
      glucomannans with molecular weights of M-n=1.0 * 10(4)-0.4 * 10(4) and degrees of
      sulfation (DS) of 1.3-1.4. It was found that the sulfated konjac glucomannans had
      potent anti-HIV activity at a 50% effective concentration, (EC50) of 1.2-1.3
      MUg/ml, which was almost as high as that of an AIDS drug, ddC, whose EC50=3.2
      MUg/ml, and moderate blood anticoagulant activity, AA=0.8-22.7 units/mg, compared
      to those of standard sulfated polysaccharides, curdlan (10 units/mg) and dextran
      (22.7 units/mg) sulfates. Structural analysis of sulfated konjac glucomannans
      with negatively charged sulfated groups was performed by high resolution NMR, and
      the interaction between poly-l-lysine with positively charged amino groups as a
      model compound of proteins and peptides was measured by surface plasmon resonance
      measurement, suggesting that the sulfated konjac glucomannans had a high binding
      stability on immobilized poly-l-lysine. The binding of sulfated konjac
      glucomannan was concentration-dependent, and the biological activity of the
      sulfated konjac glucomannans may be due to electrostatic interaction between the
      sulfate and amino groups.

PMID- 23544649
TI  - X-ray scattering studies of lignocellulosic biomass: a review.
AB  - The high processing cost of lignocellulosic ethanol is one of the most important
      barriers to its profitable commercialization. Pretreatments have been used to
      change the structure of biomass significantly and to improve sugar and ethanol
      yield. Great efforts have been made to understand the structural changes of
      biomass during these processes, including the molecular assembly of crystalline
      cellulose. Wide-angle and small-angle X-ray scattering are powerful techniques in
      studying the biomass structure at a molecular level. In this review, after we
      introduce the basic structure of lignocellulosic biomass, the effects of commonly
      used pretreatment methods on biomass structure, and the principle of X-ray
      scattering technique, the application of X-ray scattering, including studies of
      crystallinity, crystallite size, orientation distribution, and pore structure,
      and the related results in biomass conversion are summarized and discussed.
      Future study of biomass with X-ray scattering also is proposed.

PMID- 23544650
TI  - Structural elucidation of an immunoenhancing heteroglycan isolated from Russula
      albonigra (Krombh.) Fr.
AB  - A water soluble heteroglycan (PS-II) of average molecular weight ~1.45 * 10(5)Da
      was isolated from the aqueous extract of an ectomycorrhizal edible mushroom,
      Russula albonigra (Krombh.) Fr. Structural characterization of PS-II was carried
      out using acid hydrolysis, methylation analysis, periodate oxidation, and 1D/2D
      NMR studies. Structural analysis revealed that PS-II was composed of terminal 2-O
      methyl-Fucp, terminal Manp, (1->2)-Fucp, (1->3)-Glcp, (1->3,4)-Glcp, (1->6)-Galp,
      and (1->2,6)-Galp residues in a relative proportion of approximately
      1:1:1:1:1:1:1. The proposed repeating unit of the PS-II had a backbone consisting
      of two (1->3)-beta-d-glucopyranosyl, two (1->6)-alpha-d-galactopyranosyl, and one
      (1->2)-alpha-l-fucopyranosyl residues, out of which one (1->3)-beta-d
      glucopyranosyl residue was branched at O-4 position with terminal 2-O-methyl
      alpha-l-fucopyranosyl and one (1->6)-alpha-d-galactopyranosyl residue was
      branched at O-2 position with terminal alpha-d-mannopyranosyl residue. This PS-II
      showed in vitro macrophage activation by NO production as well as splenocytes and
      thymocytes proliferation.

PMID- 23544651
TI  - Effect of particle size on the surface properties and morphology of ground flax.
AB  - Flax fibers were ground with a ball-mill and four fractions with different size
      ranges were collected by sieving. These were tested for water sorption, degree of
      polymerization (DP), copper number, hydroxyl number and analyzed by X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron
      microscopy (SEM) and inverse gas chromatography (IGC). Significant differences
      were found between the properties of the flax fiber and those of the ground
      versions, including fragmentation of fibers, increase of water sorption, copper
      number, hydroxyl number and surface O/C ratio, and decrease of DP, crystallite
      size and dispersive component of surface energy (gammas(d)). Some parameters
      depended on the particle size: O/C ratio and hydroxyl number had local maxima at
      315-630 MUm, while gammas(d) increased steadily with the decrease of particle
      size. These relationships were explained by fiber disintegration, destruction of
      waxy surface layer, exposure of cellulosic components, increase of surface area
      and crystalline imperfections.

PMID- 23544652
TI  - Preparation and enzymatic hydrolysis of nanoparticles made from single xyloglucan
      polysaccharide chain.
AB  - In this work, polysaccharide nanoparticles based on tamarind seeds xyloglucan are
      prepared, analyzed in term of characteristic sizes and morphology, and degraded
      by the action of a glycoside-hydrolase. Obtained in an aqueous NaNO2 solution
      (0.1M), these unaggregated nanoparticles have a characteristic diameter of ca. 60
      nm (DLS, AFM and TEM measures). They are not compact, but highly swollen and look
      like hyperbranched and dendrimer-like (soft sphere model) structures. This
      observation is coherent with the native structure of the xyloglucan
      macromolecules which are themselves branched. The enzymatic hydrolysis by
      cellulase of Trichoderma reesei of the xyloglucan nanoparticles is investigated.
      In particular, the apparent mass molecular weight drastically decreases meaning
      that the xyloglucan nanoparticles are effectively fully hydrolyzed by the endo
      beta-(1,4)-glucanase. Furthermore, we observe that the enzyme has to uncoil the
      nanoparticles before cutting the beta-(1->4) bonds and digesting the xyloglucan.

PMID- 23544653
TI  - Scalable ionic gelation synthesis of chitosan nanoparticles for drug delivery in
      static mixers.
AB  - The purpose of this study is to synthesize chitosan (CS) nanoparticles (NPs) by
      ionic gelation with tripolyphosphate (TPP) as crossslinker in static mixers. The
      proposed static mixing technique showed good control over the ionic gelation
      process and 152-376 nm CS NPs were achieved in a continuous and scalable mode.
      Increasing the flow rates of CS:TPP solution streams, decreasing the CS
      concentration or reducing the CS:TPP solution volume ratio led to the smaller
      particles. Sylicylic acid (SA) was used as a model drug and successfully loaded
      into the CS NPs during the fabrication process. Our work demonstrates that ionic
      gelation-static mixing is a robust platform for continuous and large scale
      production of CS NPs for drug delivery.

PMID- 23544654
TI  - Ordinal judgments in the rat: an understanding of longer and shorter for
      suprasecond, but not subsecond, durations.
AB  - An emerging corpus of clinical and neuroimaging data suggests that subsecond and
      suprasecond durations are represented via 2 distinct mechanisms in humans;
      however, surprisingly, behavioral data to this effect are lacking. In our first
      experiment, we perform the first systematic exploration of subsecond and
      suprasecond timing within the same session in nonhuman subjects. Rats were
      trained to judge the relative duration of 2 sequential stimuli, responding on one
      lever if the first stimulus was longer or on a second lever if the converse was
      true. Our data provide strong evidence of an abstract understanding of longer and
      shorter for durations in the suprasecond range, whereas responding was at chance
      levels for durations in the subsecond range. Data from a second experiment reveal
      that this pattern is not due to an inability to time subsecond signals, as rats
      respond systematically in subsecond and suprasecond bisection tasks. Together,
      our results provide the first clear behavioral evidence of a discontinuity in the
      mental time line. These data from rats are discussed in light of similar findings
      of a discontinuity in the mental number line in human infants.

PMID- 23544655
TI  - Communicating with the crowd: speakers use abstract messages when addressing
      larger audiences.
AB  - Audience characteristics often shape communicators' message framing. Drawing from
      construal level theory, we suggest that when speaking to many individuals,
      communicators frame messages in terms of superordinate characteristics that focus
      attention on the essence of the message. On the other hand, when communicating
      with a single individual, communicators increasingly describe events and actions
      in terms of their concrete details. Using different communication tasks and
      measures of construal, we show that speakers communicating with many individuals,
      compared with 1 person, describe events more abstractly (Study 1), describe
      themselves as more trait-like (Study 2), and use more desirability-related
      persuasive messages (Study 3). Furthermore, speakers' motivation to communicate
      with their audience moderates their tendency to frame messages based on audience
      size (Studies 3 and 4). This audience-size abstraction effect is eliminated when
      a large audience is described as homogeneous, suggesting that people use abstract
      construal strategically in order to connect across a disparate group of
      individuals (Study 5). Finally, we show that participants' experienced fluency in
      communication is influenced by the match between message abstraction and audience
      size (Study 6).

PMID- 23544656
TI  - Computed tomography and radioprotection: knowing and acting.

PMID- 23544657
TI  - Mac Cune-Albright syndrome. Answer to the e-quid "Painful lameness in a child".

PMID- 23544659
TI  - Computational study of H2 and O2 production from water splitting by small (MO2)n
      clusters (M = Ti, Zr, Hf).
AB  - Coupled cluster [CCSD(T)] theory and density functional theory (DFT) have been
      used to study the production of H2 and O2 from hydrolysis products generated from
      H2O addition to (MO2)n (M = Ti, Zr, Hf, n = 1-3) clusters on both the lowest
      singlet and triplet potential energy surfaces (PESs). H2 production occurs via
      the formation of an M-H containing intermediate followed by H-H recombination and
      H2 desorption from M(n)O(2n)(OH)2 and M(n)O(2n+2). The hydrogen transfer
      reactions to form the M-H bond are the rate determining steps and can be
      considered to be proton coupled, electron transfer (PCET) reactions with one or
      two electrons being transferred. Oxygen is produced by breaking two weak M-O
      bonds in an atomic oxygen saturated metal oxide from an M(n)O(2n)*O2
      intermediate. On the triplet PES, the activation energies for the first and
      second H transfer to the metal are calculated to be ~10 to 50 kcal/mol and ~75 to
      90 kcal/mol depending on the size of the clusters and the metal. The barriers on
      the singlet surface for the first and the second H transfer are predicted to be
      110 to 140 kcal/mol, in general larger than the H-O bond dissociation energy. The
      activation barriers for the step of H-H recombination are 15 to 50 kcal/mol, and
      the H2 desorption energies are less than 10 kcal/mol on the singlet and triplet
      PESs. The oxygen desorption energies follow the order Ti < Zr < Hf for the
      triplets and Ti < Zr ~ Hf for the singlets. The oxygen desorption energy is
      approximately independent of the size of the cluster for the same metal. The
      water splitting reactions prefer to take place on the triplet surface. A low
      excess potential energy is needed to generate 2H2 and O2 from 2H2O after the
      endothermicity of the reaction is overcome on the triplet PES.

PMID- 23544658
TI  - Reasoning about causal relationships: Inferences on causal networks.
AB  - Over the last decade, a normative framework for making causal inferences,
      Bayesian Probabilistic Causal Networks, has come to dominate psychological
      studies of inference based on causal relationships. The following causal networks
      [X->Y->Z, X<-Y->Z, X->Y<-Z]-supply answers for questions like, "Suppose both X
      and Y occur, what is the probability Z occurs?" or "Suppose you intervene and
      make Y occur, what is the probability Z occurs?" In this review, we provide a
      tutorial for how normatively to calculate these inferences. Then, we
      systematically detail the results of behavioral studies comparing human
      qualitative and quantitative judgments to the normative calculations for many
      network structures and for several types of inferences on those networks.
      Overall, when the normative calculations imply that an inference should increase,
      judgments usually go up; when calculations imply a decrease, judgments usually go
      down. However, 2 systematic deviations appear. First, people's inferences violate
      the Markov assumption. For example, when inferring Z from the structure X->Y->Z,
      people think that X is relevant even when Y completely mediates the relationship
      between X and Z. Second, even when people's inferences are directionally
      consistent with the normative calculations, they are often not as sensitive to
      the parameters and the structure of the network as they should be. We conclude
      with a discussion of productive directions for future research.

PMID- 23544660
TI  - Setting maximum limits for trace elements in baby food in European legislation:
      the outcome of International Measurement Evaluation Programme(r)-33.
AB  - The Institute for Reference Materials and Measurements (IRMM) of the Joint
      Research Centre (JRC), a Directorate-General of the European Commission, operates
      the International Measurement Evaluation Programme(r) (IMEP). It organises
      various types of inter-laboratory comparisons in support of European Union
      policies. This paper presents the results of a proficiency testing exercise (PT)
      focusing on the determination of total cadmium (Cd) and total lead (Pb) mass
      fractions in baby food in support to Commission Regulation (EC) 1881/2006 of 19
      December 2006 setting maximum levels for certain contaminants in foodstuffs. The
      test material used in this exercise was soya-based baby food formula purchased in
      a local pharmacy and prepared by the Reference Materials Unit of the IRMM for
      this exercise. Sixty-six laboratories from 23 countries registered to the
      exercise and 61 of them reported results. Each participant received one bottle
      containing approximately 15 g of test material. Participants were asked to
      quantify the measurands in the powder and in the reconstituted formula. Reference
      values independent from the participants' results were established using isotope
      dilution inductively coupled plasma mass spectrometry. The total Cd mass fraction
      was determined by IRMM and LGC Ltd (UK), while the total Pb was determined by
      IRMM. The standard deviation for proficiency assessment sigma^ was set at 22% of
      the assigned value for all measurands. Laboratories were rated with z- and zeta-
      (zeta) scores in accordance with ISO 13528. The outcome of this exercise is
      clearly influenced by the very low level of Cd and Pb content in the test
      material which triggered: a high number of 'less than' values; overestimated
      values especially for Pb very likely due to contamination; and a visible method
      influence in the case of Pb (methods based on atomic absorption were not
      sensitive enough to attain such low limits of detection). The results were also
      evaluated with regard to the reported limit of detection and some incoherencies
      were observed.

PMID- 23544661
TI  - Global variance in female population height: the influence of education, income,
      human development, life expectancy, mortality and gender inequality in 96
      nations.
AB  - Human height is a heritable trait that is known to be influenced by environmental
      factors and general standard of living. Individual and population stature is
      correlated with health, education and economic achievement. Strong sexual
      selection pressures for stature have been observed in multiple diverse
      populations, however; there is significant global variance in gender equality and
      prohibitions on female mate selection. This paper explores the contribution of
      general standard of living and gender inequality to the variance in global female
      population heights. Female population heights of 96 nations were culled from
      previously published sources and public access databases. Factor analysis with
      United Nations international data on education rates, life expectancy, incomes,
      maternal and childhood mortality rates, ratios of gender participation in
      education and politics, the Human Development Index (HDI) and the Gender
      Inequality Index (GII) was run. Results indicate that population heights vary
      more closely with gender inequality than with population health, income or
      education.

PMID- 23544664
TI  - Layer-by-layer all-transfer-based organic solar cells.
AB  - For the first time, we describe a novel cost- and time-effective vacuum-free
      process to fabricate bulk-heterojunction (BHJ) organic photovoltaics (OPVs) via
      layer-by-layer selective stamping transfer of all layers. By controlling the
      surface properties of polyurethane acrylate (PUA) stamping molds with ultraviolet
      (UV)-ozone (UVO) exposure, poly(3,4
      ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS), BHJ layer, and metal
      cathode were uniformly transferred layer by layer onto each of the bottom layers.
      Among several interfaces between each layer, we found that the interface between
      the active layer and metal cathode is a critical factor in obtaining conventional
      device-like efficiency. To enhance the interfacial connectivity between the BHJ
      layer and metal cathode and increase electron extraction from the BHJ layer, a
      titanium oxide (TiOx) interlayer was introduced. Cell performance was optimized
      by controlling the concentration of TiOx solution. The poly(3-hexylthiophene-2,5
      diyl)/[6,6]-phenyl-C61-butyric acid methyl ester (P3HT/PC60BM) BHJ device
      fabricated by transferring PEDOT/PSS, TiOx/active layer, and Al cathode showed
      2.01% power conversion efficiency. This efficiency is not comparable to those of
      conventional OPVs, but our approach shows the possibility of fabricating OPVs via
      the layer-by-layer transfer method for the first time.

PMID- 23544662
TI  - Racial and ethnic disparities in current asthma and emergency department visits:
      findings from the National Health Interview Survey, 2001-2010.
AB  - OBJECTIVES: Racial/ethnic disparities in current asthma prevalence and medical
      care are a major public health concern. We examined the differences in asthma
      prevalence and morbidity among major racial/ethnic populations in the US.
      METHODS: We analyzed data from the 2001-2010 National Health Interview Survey for
      adults (>=18 years) and children and adolescents (<18 years). Outcome variables
      were current asthma prevalence, at least one attack in the past 12 months, and at
      least one asthma-related emergency department/urgent care center (ED/UCC) visit
      in the past 12 months. We used multivariate logistic regression to calculate the
      model-adjusted prevalence and risk ratios (ARR). RESULTS: In our study, 9.0% of
      the children and 7.2% of the adults had current asthma. Non-Hispanic black and
      Puerto Rican children were more likely to have current asthma (ARR 1.46, 1.66,
      respectively) and to visit the ED/UCC (ARR 1.61, 1.67, respectively) than non
      Hispanic whites. American Indian/Alaskan Native children were more likely to have
      current asthma (ARR 1.76) than non-Hispanic whites. Mexican/Mexican American
      children and adults had lower prevalence of current asthma but higher ED/UCC use
      (adults only) than non-Hispanic whites. Among adults, Puerto Ricans and American
      Indian/Alaskan Natives were more likely to have current asthma (ARR 1.60, 1.39,
      respectively) than non-Hispanic whites, and all the studied racial/ethnic groups
      except Asians were more likely to have visited the ED/UCC than non-Hispanic
      whites. Adults and children who received emergency care for asthma in the past 12
      months more frequently received multiple components of asthma management and
      control (e.g., taking long-term medication, having an asthma management plan)
      compared to those without emergency care. CONCLUSIONS: Racial/ethnic differences
      in current asthma prevalence, asthma attacks, and increased utilization of
      emergency room visits for asthma among minorities persist among children and
      adults. Appropriate and effective asthma management and education may lead to
      better asthma control and reduce emergency care utilization.

PMID- 23544665
TI  - TRAINER: a general-purpose trainable short biosequence classifer.
AB  - Classifying sequences is one of the central problems in computational
      biosciences. Several tools have been released to map an unknown molecular entity
      to one of the known classes using solely its sequence data. However, all of the
      existing tools are problem-specific and restricted to an alphabet constrained by
      relevant biological structure. Here, we introduce TRAINER, a new online tool
      designed to serve as a generic sequence classification platform to enable users
      provide their own training data with any alphabet therein defined. TRAINER allows
      users to select among several feature representation schemes and supervised
      machine learning methods with relevant parameters. Trained models can be saved
      for future use without retraining by other users. Two case studies are reported
      for effective use of the system for DNA and protein sequences; candidate effector
      prediction and nucleolar localization signal prediction. Biological relevance of
      the results is discussed.

PMID- 23544666
TI  - Bioinspired catecholic copolymers for antifouling surface coatings.
AB  - We report here a synthetic approach to prepare poly(methyl methacrylate)
      polydopamine diblock (PMMA-PDA) and triblock (PDA-PMMA-PDA) copolymers combining
      mussel-inspired catecholic oxidative chemistry and atom transfer radical
      polymerization (ATRP). These copolymers display very good solubility in a range
      of organic solvents and also a broad band photo absorbance that increases with
      increasing PDA content in the copolymer. Spin-cast thin films of the copolymer
      were stable in water and showed a sharp reduction (by up to 50%) in protein
      adsorption compared to those of neat PMMA. Also the peak decomposition
      temperature of the copolymers was up to 43 degrees C higher than neat PMMA. The
      enhanced solvent processability, thermal stability and low protein adsorption
      characteristics of this copolymer makes it attractive for variety of applications
      including antifouling coatings on large surfaces such as ship hulls, buoys, and
      wave energy converters.

PMID- 23544667
TI  - Self-assembling behavior of cellulose nanoparticles during freeze-drying: effect
      of suspension concentration, particle size, crystal structure, and surface
      charge.
AB  - Cellulose nanocrystals and cellulose nanofibers with I and II crystalline
      allomorphs (designated as CNC I, CNC II, CNF I, and CNF II) were isolated from
      bleached wood fibers by alkaline pretreatment and acid hydrolysis. The effects of
      concentration, particle size, surface charge, and crystal structure on the
      lyophilization-induced self-assembly of cellulose particles in aqueous
      suspensions were studied. Within the concentration range of 0.5 to 1.0 wt %,
      cellulose particles self-organized into lamellar structured foam composed of
      aligned membrane layers with widths between 0.5 and 3 MUm. At 0.05 wt %, CNC I,
      CNF I, CNC II, and CNF II self-assembled into oriented ultrafine fibers with mean
      diameters of 0.57, 1.02, 1.50, and 1.00 MUm, respectively. The size of self
      assembled fibers became larger when more hydroxyl groups and fewer sulfates
      (weaker electrostatic repulsion) were on cellulose surfaces. Possible formation
      mechanism was inferred from ice growth and interaction between cellulose
      nanoparticles in liquid-crystalline suspensions.

PMID- 23544668
TI  - The complete mitochondrial genome of the three-spot seahorse, Hippocampus
      trimaculatus (Teleostei, Syngnathidae).
AB  - The complete mitochondrial genome of the three-spot seahorse was sequenced using
      a polymerase chain reaction-based method. The total length of mitochondrial DNA
      is 16,535 bp and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA genes, and a control region. The mitochondrial gene order of the
      three-spot seahorse also conforms to the distinctive vertebrate mitochondrial
      gene order. The base composition of the genome is A (32.7%), T (29.3%), C
      (23.4%), and G (14.6%) with an A + T-rich hallmark as that of other vertebrate
      mitochondrial genomes.

PMID- 23544669
TI  - Effect of the alkyl chain length on the rotational dynamics of nonpolar and
      dipolar solutes in a series of N-alkyl-N-methylmorpholinium ionic liquids.
AB  - Rotational dynamics of two dipolar solutes, 4-aminophthalimide (AP) and 6
      propionyl-2-dimethylaminonaphthalene (PRODAN), and a nonpolar solute, anthracene,
      have been studied in N-alkyl-N-methylmorpholinium (alkyl = ethyl, butyl, hexyl,
      and octyl) bis(trifluoromethansulfonyl)imide (Tf2N) ionic liquids as a function
      of temperature and excitation wavelength to probe the microheterogeneous nature
      of these ionic liquids, which are recently reported to be more structured than
      the imidazolium ionic liquids (Khara and Samanta, J. Phys. Chem. B2012, 116,
      13430-13438). Analysis of the measured rotational time constants of the solutes
      in terms of the Stokes-Einstein-Debye (SED) hydrodynamic theory reveals that with
      increase in the alkyl chain length attached to the cationic component of the
      ionic liquids, AP shows stick to superstick behavior, PRODAN rotation lies
      between stick and slip boundary conditions, whereas anthracene exhibits slip to
      sub slip behavior. The contrasting rotational dynamics of these probe molecules
      is a reflection of their location in distinct environments of the ionic liquids
      thus demonstrating the heterogeneity of these ionic liquids. The
      microheterogeneity of these media, in particular, those with the long alkyl
      chain, is further evidence from the excitation wavelength dependence study of the
      rotational diffusion of the dipolar probe molecules.

PMID- 23544671
TI  - Direct observation of a metastable crystal phase of Li(x)FePO4 under
      electrochemical phase transition.
AB  - The phase transition between LiFePO4 and FePO4 during nonequilibrium battery
      operation was tracked in real time using time-resolved X-ray diffraction. In
      conjunction with increasing current density, a metastable crystal phase appears
      in addition to the thermodynamically stable LiFePO4 and FePO4 phases. The
      metastable phase gradually diminishes under open-circuit conditions following
      electrochemical cycling. We propose a phase transition path that passes through
      the metastable phase and posit the new phase's role in decreasing the nucleation
      energy, accounting for the excellent rate capability of LiFePO4. This study is
      the first to report the measurement of a metastable crystal phase during the
      electrochemical phase transition of LixFePO4.

PMID- 23544670
TI  - Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances
      angiogenic pathways following ischemia-reperfusion injury.
AB  - There are a limited number of therapies available to prevent heart failure
      following myocardial infarction. One novel therapy that is currently being
      pursued is the implantation of cardiac progenitor cells (CPCs); however, their
      responses to oxidative stress during differentiation have yet to be elucidated.
      The objective of this study was to determine the effect of hydrogen peroxide
      (H2O2) treatment on CPC differentiation in vitro, as well as the effect of H2O2
      preconditioning before implantation following ischemia-reperfusion (I/R) injury.
      CPCs were isolated and cloned from adult rat hearts, and then cultured in the
      absence or presence of H2O2 for 2 or 5 days. CPC survival was assessed with
      Annexin V, and cellular differentiation was evaluated through mRNA expression for
      cardiogenic genes. We found that 100 MUM H2O2 decreased serum withdrawal-induced
      apoptosis by at least 45% following both 2 and 5 days of treatment. Moreover, 100
      MUM H2O2 treatment for 2 days significantly increased endothelial and smooth
      muscle markers compared to time-matched untreated CPCs. However, continued H2O2
      treatment significantly decreased these markers. Left ventricular cardiac
      function was assessed 28 days after I/R and I/R with the implantation of
      Luciferase/GFP(+) CPCs, which were preconditioned with 100 MUM H2O2 for 2 days.
      Hearts implanted with Luciferase/GFP(+) CPCs had significant improvement in both
      positive and negative dP/dT over I/R. Furthermore, cardiac fibrosis was
      significantly decreased in the preconditioned cells versus both I/R alone and I/R
      with control cells. We also observed a significant increase in endothelial cell
      density in the preconditioned CPC hearts compared to untreated CPC hearts, which
      also coincided with a higher density of Luciferase(+) vessels. These findings
      suggest that preconditioning of CPCs with H2O2 for 2 days stimulates
      neoangiogenesis in the peri-infarct area following I/R injury and could be a
      viable therapeutic option to prevent heart failure. 

PMID- 23544672
TI  - Multivariable adaptive closed-loop control of an artificial pancreas without meal
      and activity announcement.
AB  - BACKGROUND: Accurate closed-loop control is essential for developing artificial
      pancreas (AP) systems that adjust insulin infusion rates from insulin pumps.
      Glucose concentration information from continuous glucose monitoring (CGM)
      systems is the most important information for the control system. Additional
      physiological measurements can provide valuable information that can enhance the
      accuracy of the control system. Proportional-integral-derivative control and
      model predictive control have been popular in AP development. Their
      implementations to date rely on meal announcements (e.g., bolus insulin dose
      based on insulin:carbohydrate ratios) by the user. Adaptive control techniques
      provide a powerful alternative that do not necessitate any meal or activity
      announcements. MATERIALS AND METHODS: Adaptive control systems based on the
      generalized predictive control framework are developed by extending the recursive
      modeling techniques. Physiological signals such as energy expenditure and
      galvanic skin response are used along with glucose measurements to generate a
      multiple-input-single-output model for predicting future glucose concentrations
      used by the controller. Insulin-on-board (IOB) is also estimated and used in
      control decisions. The controllers were tested with clinical studies that include
      seven cases with three different patients with type 1 diabetes for 32 or 60 h
      without any meal or activity announcements. RESULTS: The adaptive control system
      kept glucose concentration in the normal preprandial and postprandial range (70
      180 mg/dL) without any meal or activity announcements during the test period.
      After IOB estimation was added to the control system, mild hypoglycemic episodes
      were observed only in one of the four experiments. This was reflected in a plasma
      glucose value of 56 mg/dL (YSI 2300 STAT; Yellow Springs Instrument, Yellow
      Springs, OH) and a CGM value of 63 mg/dL). CONCLUSIONS: Regulation of blood
      glucose concentration with an AP using adaptive control techniques was successful
      in clinical studies, even without any meal and physical activity announcement.

PMID- 23544673
TI  - Impaired fasting glucose in hypertensive patients: prevalence and cross-sectional
      analysis of associations with cardiovascular disease.
AB  - BACKGROUND: Impaired fasting glucose (IFG) is frequently present in hypertensive
      patients and might be induced or aggravated by antihypertensive treatment.
      However, it is unclear whether IFG is associated with increased cardiovascular
      risk in this population. PATIENTS AND METHODS: We performed a cross-sectional
      study in 1,810 hypertensive patients and recorded the presence of IFG, coronary
      heart disease (CHD), and ischemic stroke. RESULTS: IFG was present in 567
      patients (31.3%). The prevalence of CHD or ischemic stroke did not differ between
      patients with IFG and in patients with serum glucose levels <100 mg/dL. Among
      patients with IFG, 267 (47.0%) were on beta-blockers, diuretics, or both beta
      blockers and diuretics. The prevalence of CHD was numerically but not
      significantly higher in patients with IFG treated with beta-blockers or both beta
      blockers and diuretics than in patients with IFG treated with diuretics or not
      treated with either beta-blockers or diuretics and patients with serum glucose
      levels <100 mg/dL (11.1%, 13.6%, 1.4%, 3.7%, and 5.9%, respectively; P=not
      significant). The prevalence of ischemic stroke did not differ among these
      groups. CONCLUSIONS: IFG does not appear to be associated with increased
      prevalence of cardiovascular disease in hypertensive patients, regardless if it
      is associated with the antihypertensive treatment or not.

PMID- 23544674
TI  - Continuous flow ion mobility separation with mass spectrometric detection using a
      nano-radial differential mobility analyzer at low flow rates.
AB  - We describe a hybrid mass-mobility instrument in which a continuous-flow ion
      mobility classifier is used as a front-end separation device for mass
      spectrometric analysis of ions generated with an electrospray ionization source.
      Using nitrogen as a carrier gas, the resolving power of the nano-radial
      differential mobility analyzer (nRDMA) for nanometer-sized ions is 5-7 for
      tetraalkylammonium ions. Data are presented demonstrating the ability of the
      system to resolve the different aggregation and charge states of
      tetraalkylammonium ions and protonated peptides using a quadrupole ion trap (QIT)
      mass spectrometer to analyze the mobility-classified ions. Specifically, data are
      presented for the two charge states of the decapeptide Gramicidin S. A key
      feature of the new instrument is the ability to continuously transmit ions with
      specific mobilities to the mass spectrometer for manipulation and analysis. 

PMID- 23544675
TI  - Do behavioural self-blame and stigma predict positive health changes in survivors
      of lung or head and neck cancers?
AB  - Survivors of lung or head and neck cancers often change tobacco and alcohol
      consumption after diagnosis, but few studies have examined other positive health
      changes (PHCs) or their determinants in these groups. The present study aims to:
      (a) document PHCs in survivors of lung (n = 107) or head and neck cancers (n =
      99) and (b) examine behavioural self-blame and stigma as determinants of PHCs. We
      hypothesised that: (a) survivors would make a variety of PHCs; (b) behavioural
      self-blame for the disease would positively predict making PHCs; and (c) stigma
      would negatively predict making PHCs. METHODS: Respondents self-administered
      measures of PHC, behavioural self-blame, and stigma. Hierarchical multiple
      regression analysis tested the hypotheses. RESULTS: More than 65% of respondents
      reported making PHCs, the most common being changes in diet (25%), exercise (23%)
      and tobacco consumption (16.5%). Behavioural self-blame significantly predicted
      PHCs but stigma did not. However, both behavioural self-blame and stigma
      significantly predicted changes in tobacco consumption. CONCLUSIONS: Many
      survivors of lung or head and neck cancers engage in PHCs, but those who do not
      attribute the disease to their behaviour are less likely to do so. Attention to
      this problem and additional counselling may help people to adopt PHCs.

PMID- 23544676
TI  - Auditory stream segregation for alternating and synchronous tones.
AB  - Sound sequences, such as music, are usually organized perceptually into
      concurrent "streams." The mechanisms underlying this "auditory streaming"
      phenomenon are not completely known. The present study sought to test the
      hypothesis that synchrony limits listeners' ability to separate sound streams. To
      test this hypothesis, both perceptual-organization judgments and performance
      measures were used. In Experiment 1, listeners indicated whether they perceived
      sequences of alternating or synchronous tones as a single stream or as two
      streams. In Experiments 2 and 3, listeners detected rare changes in the intensity
      of "target" tones at one frequency in the presence of synchronous or asynchronous
      random-intensity "distractor" tones at another frequency. The results of these
      experiments showed that, for large frequency separations between the tones, the
      probability of perceiving two streams was lower on average for synchronous than
      for alternating tones, and that sensitivity to intensity changes in the target
      sequence was greater for asynchronous than for synchronous distractors. Overall,
      these results are consistent with the hypothesis that synchrony limits listeners'
      ability to form separate streams and/or to attend selectively to certain sounds
      in the presence of other sounds, even when the target and distractor sounds are
      well separated from each other in frequency.

PMID- 23544678
TI  - Contingency management treatments decrease psychiatric symptoms.
AB  - OBJECTIVE: Contingency management (CM) is an empirically validated treatment for
      substance use disorders, but its effects on psychiatric symptoms have not been
      systematically examined. The purpose of this study was to examine the impact of
      CM on psychiatric symptoms of cocaine dependent patients receiving CM with
      standard care versus standard care alone. METHOD: Psychiatric symptoms were
      evaluated in 393 patients participating in 1 of 3 randomized trials of CM at
      treatment initiation and 1, 3 (posttreatment), 6, and 9 months later. RESULTS:
      Patients randomized to CM evidenced significant reductions in psychiatric
      symptoms over time throughout the 9-month follow-up. In contrast, psychiatric
      symptoms remained stable relative to baseline in patients randomized to standard
      care. A significant time by treatment condition effect was noted (p < .05) for
      overall psychiatric distress as well as for specific indices of depression,
      hostility, interpersonal sensitivity, phobic anxiety and psychoticism symptoms.
      Reductions in drug use mediated the effects of CM on psychiatric symptoms.
      CONCLUSIONS: These data demonstrate that the effects of CM extend beyond their
      impact on drug use behaviors and the period in which reinforcers are in effect.

PMID- 23544680
TI  - The effect of placebo tailoring on smoking cessation: a randomized controlled
      trial.
AB  - OBJECTIVE: Previous research has found that smoking cessation messages can be
      designed to appear as tailored (placebo tailored) and result in superior outcomes
      compared to standard messages. In the current study, we aimed (a) to test the
      efficacy of placebo tailoring for smoking cessation and (b) to examine the
      influence of cognitive processing style. METHOD: In a 2-arm randomized controlled
      trial, 424 smokers (M = 19.66 cigarettes per day) from the community (57% female,
      30% Caucasian, 40% African American, 29% Hispanic; mean age = 42 years) were
      randomly assigned to receive 4 placebo-tailored booklets or 4 standard booklets
      over 3 months. Participants completed a measure of systematic versus heuristic
      cognitive processing style at baseline. The primary outcome was 7-day point
      prevalence abstinence (ppa). Twenty-eight-day continuous abstinence, content
      evaluations, and readiness to quit were secondary outcomes. We hypothesized that
      placebo tailoring would be superior to standard materials and that the effect
      would be moderated by cognitive processing style (systematic and heuristic).
      RESULTS: As expected, placebo tailoring led to greater 7-day ppa at 3 months and
      greater 28-day continuous abstinence at 6 months. Cognitive processing style
      moderated the effect on 7-day ppa, such that the placebo-tailored booklets
      produced greater cessation among participants with heuristic information
      processing tendencies. CONCLUSIONS: Findings support a causal role of placebo
      tailoring for short-term smoking cessation, particularly for individuals who
      process information using heuristic strategies. Implications for tailored
      interventions are discussed.

PMID- 23544679
TI  - The predictive utility of a brief kindergarten screening measure of child
      behavior problems.
AB  - OBJECTIVE: Kindergarten teacher ratings, such as those from the Teacher
      Observation of Classroom Adaptation-Revised (TOCA-R), are a promising cost- and
      time-effective screening method to identify children at risk for later problems.
      Previous research with the TOCA-R has been mainly limited to outcomes in a single
      domain measured during elementary school. The goal of the current study was to
      examine the ability of TOCA-R sum scores to predict outcomes in multiple domains
      across distinct developmental periods (i.e., late childhood, middle adolescence,
      late adolescence). METHOD: We used data from the Fast Track Project, a large
      multisite study with children at risk for conduct problems (n = 752; M age at
      start of study = 6.55 years; 57.7% male; 49.9% Caucasian, 46.3% African
      American). Kindergarten TOCA-R sum scores were used as the predictor in
      regression analyses; outcomes included school difficulties, externalizing
      diagnoses and symptom counts, and substance use. RESULTS: TOCA-R sum scores
      predicted school outcomes at all time points, diagnosis of ADHD in 9th grade,
      several externalizing disorder symptom counts, and cigarette use in 12th grade.
      CONCLUSIONS: The findings demonstrate the predictive utility of the TOCA-R when
      examining outcomes within the school setting. Therefore, these results suggest
      the 10-item TOCA-R may provide a quick and accurate screening of children at risk
      for later problems. Implications for prevention and intervention programs are
      discussed.

PMID- 23544677
TI  - Sympathetic- and parasympathetic-linked cardiac function and prediction of
      externalizing behavior, emotion regulation, and prosocial behavior among
      preschoolers treated for ADHD.
AB  - OBJECTIVE: To evaluate measures of cardiac activity and reactivity as prospective
      biomarkers of treatment response to an empirically supported behavioral
      intervention for attention-deficit/hyperactivity disorder (ADHD). METHOD: Cardiac
      preejection period (PEP), an index of sympathetic-linked cardiac activity, and
      respiratory sinus arrhythmia (RSA), an index of parasympathetic-linked cardiac
      activity, were assessed among 99 preschool children (ages 4-6 years) with ADHD
      both at rest and in response to behavioral challenge, before participants and
      their parents completed 1 of 2 versions of the Incredible Years parent and child
      interventions. RESULTS: Main effects of PEP activity and reactivity and of RSA
      activity and reactivity were found. Although samplewide improvements in behavior
      were observed at posttreatment, those who exhibited lengthened cardiac PEP at
      rest and reduced PEP reactivity to incentives scored higher on measures of
      conduct problems and aggression both before and after treatment. In contrast,
      children who exhibited lower baseline RSA and greater RSA withdrawal scored lower
      on prosocial behavior before and after treatment. Finally, children who exhibited
      greater RSA withdrawal scored lower on emotion regulation before and after
      treatment. CONCLUSIONS: We discuss these findings in terms of (a) individual
      differences in underlying neurobiological systems subserving appetitive (i.e.,
      approach) motivation, emotion regulation, and social affiliation and (b) the need
      to develop more intensive interventions targeting neurobiologically vulnerable
      children.

PMID- 23544681
TI  - Behavioral medicine and clinical health psychology: introduction to the special
      issue.
AB  - This issue represents the 4th Journal of Consulting and Clinical Psychology
      special issue on behavioral medicine and clinical health psychology over the past
      4 decades. Recent developments in health care policy, as well as in the
      maturation of the science, make a special issue in this area particularly timely.
      This collection includes state of the clinical science reviews, reports of
      clinical trials, and articles addressing theory and methods in behavioral
      medicine and clinical health psychology. A multilevel, ecological perspective
      that considers multiple levels of influences (e.g., cultural influences on
      behavior-health linkages, individual differences) is salient throughout many of
      the articles. Our hope is that this sampling of this broad field, and coverage of
      some key issues and areas, will play a role in stimulating the next 10 years of
      research, practice, and policy implementation in behavioral medicine and clinical
      health psychology.

PMID- 23544682
TI  - Climbing the level of evidence ladder: prospective, comparative-effectiveness
      knee ACL and PCL research.

PMID- 23544683
TI  - Suture bridge fixation for tibial eminence fractures.

PMID- 23544684
TI  - Author's reply: To PMID 22607830.

PMID- 23544685
TI  - Is it lateral retinacular lengthening versus lateral retinacular release or over
      release?

PMID- 23544686
TI  - Author's reply: To PMID 22301361.

PMID- 23544687
TI  - Comprehensive Arthroscopic Management (CAM) procedure: clinical results of a
      joint-preserving arthroscopic treatment for young, active patients with advanced
      shoulder osteoarthritis.
AB  - PURPOSE: The purpose of this study was to examine the surgical outcomes of 29
      active patients (30 shoulders) with end-stage, symptomatic glenohumeral arthritis
      undergoing the comprehensive arthroscopic management (CAM) procedure. METHODS: In
      this institutional review board-approved study, patients with advanced
      glenohumeral osteoarthritis (OA) underwent the CAM procedure, a joint-preserving
      arthroscopic treatment. All subjects were candidates for shoulder arthroplasty.
      The CAM procedure involves the combination of glenohumeral chondroplasty; removal
      of loose bodies if present; humeral osteoplasty and osteophyte resection (goat's
      beard deformity); anterior, posterior, and inferior capsular release; subacromial
      decompression; axillary nerve neurolysis; and biceps tenodesis. Outcome measures
      included pain, American Shoulder and Elbow Surgeons score, Single Assessment
      Numeric Evaluation score, QuickDASH (short version of Disabilities of the Arm,
      Shoulder and Hand questionnaire) score, and satisfaction. For survivorship
      analysis, failure was defined as progression to shoulder arthroplasty. RESULTS:
      The mean age was 52 years (range, 33 to 68 years), and there were 23 men and 6
      women. Of the 30 shoulders, 6 progressed to an arthroplasty at a mean of 1.9
      years (range, 0.9 to 3.4 years). Patients with less than 2.0 mm of joint space on
      radiographs were more likely to undergo arthroplasty (P = .037). For shoulders
      that did not progress to arthroplasty (n = 24), the mean follow-up was 2.6 years
      (range, 2.1 to 4.7 years). The American Shoulder and Elbow Surgeons scores
      significantly improved from 58 points (SE, 2.4) to 83 points (SE, 3.3) (P <
      .001), and pain levels decreased with activities of daily living, work,
      recreation, and sleep (P < .05). The median patient satisfaction rating was 9
      (range, 3 to 10). Survivorship analysis showed a 92% survival rate at 1 year and
      85% at 2 years. Patients with larger osteophytes had greater improvement in
      postoperative range of motion but were less satisfied (r = 0.479, P = .038).
      CONCLUSIONS: The CAM procedure reduced pain, improved function, and provided
      reasonable short-term durability for our cohort of young, active patients with
      advanced shoulder OA and may serve as a joint-preserving alternative to
      arthroplasty. Patients with less than 2 mm of joint space had a significantly
      higher failure rate. The CAM procedure is a viable surgical option in young,
      active patients with advanced OA, showing survivorship of 85% at 2 years. LEVEL
      OF EVIDENCE: Level IV, therapeutic case series.

PMID- 23544688
TI  - Open versus arthroscopic meniscus allograft transplantation: magnetic resonance
      imaging study of meniscal radial displacement.
AB  - PURPOSE: In this imaging study, the radial displacement of meniscal allograft
      transplants (MATs), inserted with 2 different techniques, namely open soft-tissue
      fixation and arthroscopic bone tunnel fixation, was compared 1 year
      postoperatively. METHODS: In this study, 37 patients received MATs: 16 MATs (10
      lateral and 6 medial) were inserted by an open soft-tissue technique (open MATs),
      whereas 21 MATs (14 lateral and 7 medial) were implanted by an arthroscopic bone
      tunnel procedure (arthroscopic MATs). Radial displacement, in millimeters, was
      evaluated 1 year postoperatively on 1.5-T magnetic resonance images. The number
      of MATs with radial displacement larger or smaller than 3 mm was determined. To
      compare radial displacement of open versus arthroscopic MATs, the Mann-Whitney U
      test was used. RESULTS: The radial displacement of open lateral and medial MATs
      was significantly larger (all reported P < .02) than that of arthros-copic MATs.
      In all cases, both open and arthroscopic, the radial displacement of MATs was
      significantly larger (all reported P < .007) than that of normal menisci. Radial
      displacement of less than 3 mm was found in 0 of 6 patients with open medial MATs
      versus 6 of 7 patients with arthroscopic MATs and was found in 1 of 10 patients
      with open lateral MATs versus 4 of 14 patients with arthroscopic MATs.
      CONCLUSIONS: The radial displacement of MATs arthroscopically inserted with bone
      tunnel fixation is significantly less than the radial displacement of MATs
      inserted with open soft-tissue fixation. In addition, normal menisci displace
      significantly less than meniscal allografts. The clinical importance of radial
      displacement remains to be determined. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 23544689
TI  - Anterior cruciate ligament reconstruction femoral tunnel characteristics using an
      accessory medial portal versus traditional transtibial drilling.
AB  - PURPOSE: To evaluate anterior cruciate ligament femoral tunnel characteristics
      using an accessory medial (AM) portal and transtibial (TT) drilling. METHODS: Ten
      matched pairs of cadaveric knees underwent arthroscopic AM portal or TT femoral
      drilling with 8-mm reamers. All knees underwent computed tomography scanning and
      were evaluated for tunnel aperture area, shape as described by the length of the
      long and short axes, location of the tunnel relative to the anterior and inferior
      aspects of the articular surface with the knee in extension, tunnel angle in the
      coronal and axial planes, and tunnel length. RESULTS: The femoral tunnel aperture
      area was 50.5 +/- 4.8 mm(2) for AM portal drilling and 51.9 +/- 4.6 mm(2) for TT
      drilling (P = .5). The femoral tunnel aperture long axis was 8.5 +/- 1.1 mm for
      AM portal drilling and 9.2 +/- 1.3 mm for TT drilling (P = .2), and the short
      axis was 8.0 +/- 0.5 mm for AM portal drilling and 8.0 +/- 0.5 mm for TT drilling
      (P = .8). The femoral tunnel aperture was 5.0 +/- 1.4 mm from the anterior wall
      for AM portal drilling and 9.9 +/- 1.7 mm for TT drilling (P < .001), and it was
      7.6 +/- 2.4 mm from the inferior articular surface for AM portal drilling and 8.9
      +/- 2.2 mm for TT drilling (P = .2). The femoral tunnel orientation in the
      coronal plane was 42.1 degrees  +/- 4.8 degrees  for AM portal drilling and 60.9
      degrees  +/- 6.7 degrees  for TT drilling (P < .001), and the orientation in the
      axial plane was 20.9 degrees  +/- 4.4 degrees  for AM portal drilling and 22.7
      degrees  +/- 13.5 degrees  for TT drilling (P = .7). The femoral tunnel length
      was 35.6 +/- 2.8 mm for AM portal drilling and 40.3 +/- 7.9 mm for TT drilling (P
      = .1). CONCLUSIONS: The use of an AM portal creates a tunnel more anterior and
      more horizontal than tunnels created by a TT technique. CLINICAL RELEVANCE: The
      femoral tunnel characteristics may have an effect on the strain placed on the
      graft, the graft bending angle, whether enough graft can be placed into the
      tunnel, and, ultimately, the ability of the body to fully heal the graft.

PMID- 23544690
TI  - Outcomes of osteochondral allograft transplantation in the knee.
AB  - PURPOSE: The objectives of this study were (1) to conduct a systematic review of
      clinical outcomes after osteochondral allograft transplantation in the knee and
      (2) to identify patient-, defect-, and graft-specific prognostic factors.
      METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register
      of Controlled Trials. Studies that evaluated clinical outcomes in adult patients
      after osteochondral allograft transplantation for chondral defects in the knee
      were included. Pooled analyses for pertinent continuous and dichotomous variables
      were performed where appropriate. RESULTS: There were 19 eligible studies
      resulting in a total of 644 knees with a mean follow-up of 58 months (range, 19
      to 120 months). The overall follow-up rate was 93% (595 of 644). The mean age was
      37 years (range, 20 to 62 years), and 303 patients (63%) were men. The methods of
      procurement and storage time included fresh (61%), prolonged fresh (24%), and
      fresh frozen (15%). With regard to etiology, the most common indications for
      transplantation included post-traumatic (38%), osteochondritis dissecans (30%),
      osteonecrosis from all causes (12%), and idiopathic (11%). Forty-six percent of
      patients had concomitant procedures, and the mean defect size across studies was
      6.3 cm(2). The overall satisfaction rate was 86%. Sixty-five percent of patients
      (72 of 110) showed little to no arthritis at final follow-up. The reported short
      term complication rate was 2.4%, and the overall failure rate was 18%.
      Heterogeneity in functional outcome measures precluded a meta-analysis; a
      qualitative synthesis allowed for the identification of several positive and
      negative prognostic factors. CONCLUSIONS: Osteochondral allograft transplantation
      for focal and diffuse (single-compartment) chondral defects results in
      predictably favorable outcomes and high satisfaction rates at intermediate follow
      up. Patients with osteochondritis dissecans and traumatic and idiopathic
      etiologies have more favorable outcomes, as do younger patients with unipolar
      lesions and short symptom duration. Future studies should include comparative
      control groups and use established outcome instruments that will allow for
      pooling of data across studies. LEVEL OF EVIDENCE: Level IV, systematic review of
      Level IV studies.

PMID- 23544691
TI  - Complications and reoperations during and after hip arthroscopy: a systematic
      review of 92 studies and more than 6,000 patients.
AB  - PURPOSE: To determine the prevalence of complications and reoperations during and
      after hip arthroscopy. METHODS: A systematic review of multiple medical databases
      was performed using the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines and checklist. All clinical outcome studies that
      reported the presence or absence of complications and/or reoperations were
      eligible for inclusion. Length of follow-up was not an exclusion criterion.
      Complication and reoperation rates were extracted from each study. Duplicate
      patient populations within separate distinct publications were analyzed and
      reported only once. RESULTS: Ninety-two studies (6,134 participants) were
      included. Most were Level IV evidence studies (88%) with short-term follow-up
      (mean 2.0 years). Labral tears and femoroacetabular impingement (FAI) were the 2
      most common diagnoses treated, and labral treatment and acetabuloplasty/femoral
      osteochondroplasty were the 2 most common surgical techniques reported. Overall,
      major and minor complication rates were 0.58% and 7.5%, respectively. Iatrogenic
      chondrolabral injury and temporary neuropraxia were the 2 most common minor
      complications. The overall reoperation rate was 6.3%, occurring at a mean of 16
      months. Total hip arthroplasty (THA) was the most common reoperation. The
      conversion rate to THA was 2.9%. CONCLUSIONS: The rate of major complications was
      0.58% after hip arthroscopy. The reoperation rate was 6.3%, and the most common
      reason for reoperation was conversion to THA. Minor complications and the
      reoperation rate are directly related to the learning curve of hip arthroscopy.
      As surgical indications evolve, patient selection should limit the number of
      cases that would have been converted to THA. Similarly, the number of minor
      complications is directly related to technical aspects of the procedure and
      therefore will decrease with surgeon experience and improvement in
      instrumentation. LEVEL OF EVIDENCE: Level IV, a systematic review of Level I to
      IV studies.

PMID- 23544698
TI  - Theoretical strategy to build structural models of microhydrated inorganic
      systems for the knowledge of their vibrational properties: the case of the
      hydrated nitrate aerosols.
AB  - This study provides theoretical anharmonic calculations for microhydrated NaNO3
      labeled (NaNO3, nH2O)x with a water-to-solute ratio (n) ranging from 1 to 3. A
      representative geometrical model of these forms was first investigated by
      simulating the molecular clusters as (NaNO3,1H2O)x with x = 1 to 4. The
      comparison between the calculated time independent anharmonic frequencies using
      the B3LYP-D/6-311+G(d,p) method and their experimental counterparts led to the
      choice of a supercluster model. The most probable structures of (NaNO3,nH2O)3
      molecular system were investigated by using our global search algorithm we
      developed recently (GSAM code) both at the B3LYP/6-311+G(d,p) and the B3LYP-D/6
      311+G(d,p) levels of theory. The quality of the structural model is illustrated
      by comparing the B3LYP/6-311+G(d,p) and B3LYP-D/6-311+G(d,p) anharmonic
      vibrational signatures with those obtained from IR experiments. While an average
      deviation of 16 cm(-1) is observed in the case of the B3LYP computations, the
      deviation is reduced to 7 cm(-1) for the B3LYP-D computations. 

PMID- 23544697
TI  - Sonographically suspicious thyroid nodules with initially benign cytologic
      results: the role of a core needle biopsy.
AB  - PURPOSE: To evaluate the diagnostic role of core needle biopsy (CNB) in
      sonographically suspicious thyroid nodules with initially benign cytologic
      results through a histologic analysis of CNB specimens. METHODS: Between October
      2008 and July 2011, 88 patients underwent ultrasound (US)-guided CNB for
      initially benign cytologic results with suspicious US features at our
      institution. In all, 85 patients with 85 focal thyroid nodules were included in
      the study after surgery or concordant benign readings following fine-needle
      aspiration biopsy (FNAB) and CNB. We evaluated the risk of malignancy, diagnostic
      performance of CNB, and histologic findings for these nodules. RESULTS: Of the 85
      nodules, 28 (32.9%) were histologically upgraded on CNB specimens including one
      case of atypia of undetermined significance (AUS), seven cases of follicular
      neoplasm, one case of suspicious for malignancy, and 19 cases of malignancy. Of
      these, 27 (31.8%) were finally confirmed as malignant, and one as follicular
      adenoma at surgery. The 27 malignant nodules included 21 papillary thyroid
      carcinomas (PTCs), five follicular thyroid carcinomas, and one Hurthle cell
      carcinoma. All PTCs were diagnosed from CNB readings of AUS suspicious for
      malignancy or malignancy. Follicular thyroid carcinomas and Hurthle cell
      carcinoma were diagnosed from CNB readings of follicular neoplasm. Histologic
      analysis of benign CNB specimens revealed severe fibrosis (96.4%), hemosiderin
      (21.4%), calcification (17.9%), granulation tissue (12.5%), and focal lymphocytic
      thyroiditis (12.5%). CONCLUSIONS: The histologic information obtained by analysis
      of CNB specimens may enable more confident diagnosis for benign nodules with
      suspicious US features and reduce the need for repetitive FNABs or diagnostic
      surgery.

PMID- 23544701
TI  - Enantioselective synthesis of 4-heterosubstituted cyclopentenones.
AB  - Racemic 4-hydroxycyclopentenone, readily derived from furfuryl alcohol, can be
      transformed via its O-Boc derivative to 4-acyloxy, 4-aryloxy-, 4-amino-, or 4
      thio-substituted cyclopentenones with high enantioselectivity by palladium
      catalyzed kinetic resolution via nucleophilic allylic substitutions. Applying
      this methodology, a short formal synthesis of ent-noraristeromycin was readily
      accomplished.

PMID- 23544702
TI  - The management of recurrent croup in children.
AB  - OBJECTIVE: To review the aetiology, investigation, diagnosis, treatment and
      clinical outcome of children with recurrent croup. METHOD: Retrospective case
      note review of all children with recurrent croup referred to the otolaryngology
      service at our hospital from November 2002 to March 2011. RESULTS: Ninety
      children with recurrent croup were identified. Twenty-five children (28 per cent)
      had anatomical airway abnormalities, of which 16 (18 per cent) demonstrated
      degrees of subglottic stenosis. Twenty-three children (26 per cent) had positive
      microlaryngobronchoscopy findings suggestive of reflux. Eleven children were
      treated for gastroesophageal reflux disease, 10 (91 per cent) of whom responded
      well to anti-reflux medication (p = 0.006). No cause was identified for 41 (45
      per cent) of the children; this was the group most likely to continue having
      episodes of croup at follow up. One death occurred in this group. CONCLUSION:
      Airway anomalies are common in children that present with recurrent croup.
      Laryngobronchoscopy allows identification of the cause of croup and enables a
      more accurate prognosis. In the current study, laryngobronchoscopy findings that
      indicated reflux were predictive of benefit from anti-reflux medications, whereas
      the clinical presentation of reflux was not. Routine measurement of
      immunoglobulin E and complement proteins did not appear to be helpful.

PMID- 23544703
TI  - Physiotherapy in asthma--seeking consensus.
AB  - OBJECTIVE: The evidence base for or against physiotherapy interventions in
      asthmatic adults remains ambiguous, and there are discrepancies between different
      clinical practice guidelines. We evaluated the level of agreement between the
      recommendations about physiotherapy for adults with asthma in two major clinical
      practice guidelines: the Global Initiative for Asthma (GINA 2011) and the British
      Thoracic Society and the Association of Chartered Physiotherapists in Respiratory
      Care (BTS/ACPRC 2009). METHODS: We used the Appraisal of Guidelines for Research
      & Evaluation (AGREE II) instrument to assess the methodological rigor of the
      guideline development, the Assessment of Multiple Systematic Reviews (AMSTAR)
      tool and the Physiotherapy Evidence Database (PEDro) scale to assess the
      methodological quality of systematic reviews and clinical trials included in the
      analyzed documents. Additionally, we compared the reference lists of the analyzed
      sections to establish the overlap in included primary and secondary studies.
      RESULTS: We observed no agreement between the two guidelines in the choice of
      source research articles. Only two studies out of 18 used in BTS guidelines were
      used in the GINA. The reason why GINA developers did not use the body of evidence
      included in BTS is that it is not clear. Three independent investigators
      indicated higher scores in all domains of the AGREE II in the BTS/ACPRC document
      in comparison with the GINA guidelines. CONCLUSIONS: The significant differences
      in the content and in the development processes of the examined sections of the
      two guidelines suggest the need for more frequent and careful updating or
      directing the readers of the GINA to the BTS/ACPRC, a guideline addressing
      specifically and more comprehensively physiotherapy interventions in asthma.

PMID- 23544704
TI  - Production of viable cloned miniature pigs by aggregation of handmade cloned
      embryos at the 4-cell stage.
AB  - The aim of the present study was to improve the quality of handmade cloned
      porcine embryos by multiple embryo aggregations. Embryos derived from aggregation
      of three cloned embryos (3*) had a better blastocyst rate than cloned control
      (1*) embryos (73.6% vs 35.1%, respectively; P<0.05), but did not differ from
      those produced by aggregation of two cloned embryos (2*; 63.0%). Total cell
      numbers differed among treatments (P<0.05), with the greatest cell numbers (126)
      in the 3* group and the lowest (55) in the control group. The ratio of inner cell
      mass:total cell number was comparable in the 2* and 3* groups (25.1% vs 26.1%,
      respectively) and was significantly better than that in the control group
      (15.3%). The proportion of apoptotic cells in 2* and 3* groups was lower than
      that in the control group (2.7% and 2.2% vs 4.7%, respectively; P<0.05).
      Expression of Oct4 and Cdx2 was higher, whereas that of Bax was lower (P<0.05),
      in the 3* compared with non-aggregate group. Seven piglets were born to two
      surrogate mothers after embryo transfer of 3* aggregated blastocysts. In
      conclusion, aggregated embryos had greater total cell numbers and better
      pluripotency gene expression, with reduced expression of the pro-apoptosis gene
      Bax. Collectively, these improvement may be associated with the development of
      cloned embryos to term. 

PMID- 23544705
TI  - Density functional theory predictions of the composition of atomic layer
      deposition-grown ternary oxides.
AB  - The surface reactivity of various metal precursors with different alkoxide,
      amide, and alkyl ligands during the atomic layer deposition (ALD) of ternary
      oxides was determined using simplified theoretical models. Quantum chemical
      estimations of the Bronsted reactivity of a metal complex precursor at a
      hydroxylated surface are made using a gas-phase hydrolysis model. The geometry
      optimized structures and energies for a large suite of 17 metal precursors
      (including cations of Mg, Ca, Sr, Sc, Y, La, Ti, Zr, Cr, Mn, Fe, Co, Ni, Cu, Zn,
      Al, and Ga) with five different anionic ligands (conjugate bases of tert-butanol,
      tetramethyl heptanedione, dimethyl amine, isopropyl amidine, and methane) and the
      corresponding hydrolyzed complexes are calculated using density functional theory
      (DFT) methods. The theoretically computed energies are used to determine the
      energetics of the model reactions. These DFT models of hydrolysis are used to
      successfully explain the reactivity and resulting stoichiometry in terms of metal
      cation ratios seen experimentally for a variety of ALD-grown ternary oxide
      systems.

PMID- 23544706
TI  - Genetic structure of a Japanese brown frog (Rana japonica) population implies
      severe restriction of gene flow caused by recent urbanization in a satoyama
      landscape.
AB  - Rapid urbanization is one of the major pressures on amphibian species.
      Elucidating changes in genetic structure will be useful in evaluating the effects
      of urbanization on amphibian populations. Our study focused on Rana japonica,
      which is common in complex agricultural landscapes known as satoyama, which are
      also under intense development pressure. We conducted landscape genetic analyses
      based on mitochondrial DNA haplotype frequencies of 13 breeding sites in a
      rapidly urbanizing area of Japan. We found several breeding sites had
      significantly higher F(st) values, and we also identified the barriers to gene
      flow between these sites. Observation of past aerial photographs revealed that
      these barriers coincided with the construction of man-made structures in the last
      few decades, suggesting that urbanization has restricted gene flow in R.
      japonica. Our results show that landscape genetic approaches are useful in
      conservation planning where rapid habitat degradation has taken place.

PMID- 23544707
TI  - The role of omega-3 polyunsaturated fatty acids supplementation in childhood: a
      review.
AB  - Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) benefits are not
      clearly defined in childhood although already well-defined in adults. Recent
      studies have demonstrated their positive effects on bronchial asthma,
      neuropsychiatric disorders and cognitive brain function in childhood.
      Furthermore, it has been demonstrated as a relationship between the increased
      incidence of childhood obesity and the role of omega-3 PUFAs in reducing the
      metabolic and vascular alterations induced by the fat accumulation since young
      age. Such relationship could be more important in prevention of future
      cardiovascular events. In fact, omega-3 PUFAs could improve endothelial function
      and structure since childhood. By considering endothelial dysfunction as a well
      known early marker of atherosclerosis, its amelioration in the beginning years of
      individuals' life will certainly reduce the cardiovascular risk profile in
      adulthood. Nevertheless, their use is limited by several factors, such as the
      lack of studies in children and the awful taste of the products enriched with
      omega-3 PUFAs, although several patents have managed to overcome such defects and
      developed the use of these molecules. This paper is a literature study and
      patents analysis aiming to explore key issues regarding omega-3 PUFAs
      administration in childhood in order to take into account its routine intake
      daily. However, it is well-established that further studies are needed to endorse
      the promising results outlined by literature analysis. 

PMID- 23544709
TI  - Particle deformation and concentration polarization in electroosmotic transport
      of hydrogels through pores.
AB  - In this article, we report detection of deformable, hydrogel particles by the
      resistive-pulse technique using single pores in a polymer film. The hydrogels
      pass through the pores by electroosmosis and cause formation of a characteristic
      shape of resistive pulses indicating the particles underwent dehydration and
      deformation. These effects were explained via a non-homogeneous pressure
      distribution along the pore axis modeled by the coupled Poisson-Nernst-Planck and
      Navier-Stokes equations. The local pressure drops are induced by the
      electroosmotic fluid flow. Our experiments also revealed the importance of
      concentration polarization in the detection of hydrogels. Due to the negative
      charges as well as branched, low-density structure of the hydrogel particles, the
      concentration of ions in the particles is significantly higher than in the bulk.
      As a result, when an electric field is applied across the membrane, a depletion
      zone can be created in the vicinity of the particle observed as a transient drop
      of the current. Our experiments using pores with openings between 200 and 1600 nm
      indicated the concentration polarization dominated the hydrogels' detection of
      pores wider than 450 nm. The results are of importance for all studies that
      involve transport of molecules, particles, and cells through pores with charged
      walls. The developed inhomogeneous pressure distribution can potentially
      influence the shape of the transported species. The concentration polarization
      changes the interpretation of the resistive pulses; the observed current change
      does not necessarily reflect only the particle size but also the size of the
      depletion zone that is formed in the particle vicinity.

PMID- 23544710
TI  - Trans effect in halobismuthates and haloantimonates revisited. Molecular
      structures and vibrations from theoretical calculations.
AB  - Ab initio and density functional theory computations have been carried out to
      calculate the structures and vibrational spectra of halobismuthates and
      haloantimonates of formulas MX6(3-), M2X10(4-), and M2X9(3-) for M = Bi or Sb and
      X = I, Br, or Cl. The results have been compared to experimental crystal
      structures and the infrared and Raman spectra of these species as well as the
      (MX5(2-))n and (MX4(1-))n anions. Even though the calculations neglect the effect
      of which cation is present, they do a good job in verifying the observed trends
      in bond distances and bond stretching vibrational frequencies. External bonds
      across from bridging bonds are the shortest and have the highest stretching
      frequencies for all of the ions investigated. This supports the previously
      postulated "trans effect". Since the calculations were carried out for individual
      noninteracting anions, the computed results can be expected to best represent the
      idealized species unperturbed by the effect of the cations present. The trans
      effect results in shortening of the M-X bonds by 0.08-0.13 A. It also leads to
      frequency increases of about 20% for the M-X stretching vibrations.

PMID- 23544708
TI  - Functional proteome of macrophage carried nanoformulated antiretroviral therapy
      demonstrates enhanced particle carrying capacity.
AB  - Our laboratory developed long-acting nanoformulations of antiretroviral therapy
      (nanoART) to improve drug compliance, reduce toxicities, and facilitate access of
      drug to viral reservoirs. These all function to inevitably improve treatment of
      human immunodeficiency virus (HIV) infection. Formulations are designed to
      harness the carrying capacities of mononuclear phagocytes (MP; monocytes and
      macrophages) and to use these cells as Trojan horses for drug delivery. Such a
      drug distribution system limits ART metabolism and excretion while facilitating
      access to viral reservoirs. Our prior works demonstrated a high degree of nanoART
      sequestration in macrophage recycling endosomes with broad and sustained drug
      tissue biodistribution and depots with limited untoward systemic toxicities.
      Despite such benefits, the effects of particle carriage on the cells' functional
      capacities remained poorly understood. Thus, we employed pulsed stable isotope
      labeling of amino acids in cell culture to elucidate the macrophage proteome and
      assess any alterations in cellular functions that would affect cell-drug carriage
      and release kinetics. NanoART-MP interactions resulted in the induction of a
      broad range of activation-related proteins that can enhance phagocytosis,
      secretory functions, and cell migration. Notably, we now demonstrate that
      particle-cell interactions serve to enhance drug loading while facilitating drug
      tissue depots and transportation.

PMID- 23544711
TI  - Unraveling the enigmatic mechanism of L-asparaginase II with QM/QM calculations.
AB  - In this paper, we have studied the catalytic mechanism of L-asparaginase II
      computationally. The reaction mechanism was investigated using the ONIOM
      methodology. For the geometry optimization we used the B3LYP/6-31G(d):AM1 level
      of theory, and for the single points we used the M06-2X/6-311++G(2d,2p):M06-2X/6
      31G(d) level of theory. It was demonstrated that the full mechanism involves
      three sequential steps and requires the nucleophilic attack of a water molecule
      on the substrate prior to the release of ammonia. There are three rate-limiting
      states, which are the reactants, the first transition state, and the last
      transition state. The energetic span is 20.2 kcal/mol, which is consistent with
      the experimental value of 16 kcal/mol. The full reaction is almost thermoneutral.
      The proposed catalytic mechanism involves two catalytic triads that play
      different roles in the reaction. The first triad, Thr12-Lys162-Asp90, acts by
      deprotonating a water molecule that subsequently binds to the substrate. The
      second triad, Thr12-Ty25-Glu283, acts by stabilizing the tetrahedral intermediate
      that is formed after the nucleophilic attack of the water molecule to the
      substrate. We have shown that a well-known Thr12-substrate covalent intermediate
      is not formed in the wild-type mechanism, even though our results suggest that
      its formation is expected in the Thr89Val mutant. These results have provided a
      new understanding of the catalytic mechanism of L-asparaginases that is in
      agreement with the available experimental data, even though it is different from
      all earlier proposals. This is of particular importance since this enzyme is
      currently used as a chemotherapeutic drug against several types of cancer and in
      the food industry to control the levels of acrylamide in food.

PMID- 23544712
TI  - Advanced systems for glucocorticoids' dermal delivery.
AB  - INTRODUCTION: Although the skin provides a natural physical barrier against
      particle penetration, there are opportunities to deliver therapeutic agents
      through this barrier. With rapid developments in materials science,
      pharmaceutics, and biotechnology, new systems have emerged for topical
      glucocorticoids (TG) delivery. Despite being a mature class of drugs, TG are
      still the most frequently prescribed drugs by dermatologists, explaining the
      interest on this field. AREAS COVERED: Over the years, research has focused on
      strategies to optimize the potency of steroids while minimizing adverse effects.
      Several attempts have been made to increase the safety of TG treatment, including
      new application schedules, special vehicles, and new synthesized agents. This
      paper gives an overview on the conventional and advanced vehicles used to deliver
      TG, including strategies to improve the delivery and accumulation of TG. The
      therapeutic advantages of TG delivery to the epidermis are discussed with a
      special focus on new drug-delivery systems for topical application. EXPERT
      OPINION: New technologies have been developed for TG delivery, and studies are
      currently underway in order to obtain improved benefit/risk ratio. A rationale
      development approach that integrates simple formulations would help to develop
      vehicles with these features.

PMID- 23544713
TI  - Activity-based DNA-gold nanoparticle probe as colorimetric biosensor for DNA
      methyltransferase/glycosylase assay.
AB  - We have developed a novel biosensor platform for colorimetric detection of active
      DNA methyltransferase/glycosylase based on terminal protection of the DNA-gold
      nanoparticle (AuNP) probes by mechanistically covalent trapping of target
      enzymes. This biosensor relied on covalent capture of target enzymes by activity
      based DNA probes which created terminal protection of the DNA probes tethered on
      AuNPs from degradation by Exo I and III. This biosensor has the advantages of
      having highly sensitive, rapid, and convenient detection due to its use of the
      homogeneous assay format and strong surface plasmon absorption. Because the
      activity-based probes (ABPs) are mechanistically specific to target enzymes, this
      strategy also offers improved selectivity and can achieve the information about
      both abundance and activity of the enzymes. We have demonstrated this strategy
      using a human DNA (cytosine-5) methyltransferase (Dnmt 1) and a human 8
      oxoguanine glycosylase (hOGG 1). The results reveal that the colorimetric
      response increases dynamically with increasing activity of the enzymes, implying
      a great potential of this strategy for DNA methyltransferase/glycosylase
      detection and molecular diagnostics and drug screening. Our strategy can also be
      used as a promising and convenient approach for visualized screening of ABPs for
      DNA modifying enzymes. 

PMID- 23544714
TI  - Impact of high basal FSH/LH ratio in women with normal FSH levels on in vitro
      fertilization outcomes.
AB  - Basal luteinizing hormone (LH) levels have also been suggested to impact on
      ovarian responsiveness as well as basal follicular stimulating hormone (FSH)
      levels. The aim of this study was to compare the in vitro fertilization (IVF)
      outcomes according to cycle day 3 FSH/LH ratio and to assess the proper
      stimulation protocol between gonadotropin-releasing hormone (GnRH) agonist and
      GnRH antagonist protocols. The retrospective cohort study recruited a total of
      1211 women having the laboratory values of FSH (<10 IU/L) and LH within 3 months
      before IVF. Patients were treated with GnRH agonist long or GnRH antagonist
      protocols and stimulated with recombinant FSH (rFSH). The number of total
      retrieved oocytes and mature oocytes, implantation rate, clinical pregnancy rate
      and ongoing pregnancy rate were analyzed between groups: Group I: FSH/LH < 2 and
      Group II: FSH/LH >= 2. The Group II had the small number of retrieved oocytes and
      mature oocytes compared to the Group I (p = 0.000). Clinical and ongoing
      pregnancy rate were lower in Group II (p = 0.006, 0.006, respectively). In
      comparison of each protocol within groups, Group II showed significantly low
      pregnancy rate when GnRH antagonist was administered. In women with normal FSH
      level, high day 3 FSH/LH ratio can present subclinically low ovarian reserve and
      be predictive of lower pregnancy outcomes in fresh IVF cycles, and the choice of
      GnRH agonist can be related to favorable IVF outcomes.

PMID- 23544715
TI  - Abdominal adiposity through adipocyte secretion products, a risk factor for
      endometrial cancer.
AB  - BACKGROUND AND AIM: The adipose cell has been considered an inert cell from a
      secretory point of view. Studies over the past years have confirmed the capacity
      of the adipocyte to synthesize many substances including: adiponectin, leptin,
      which integrate multiple metabolic and endocrine signals. In the context of
      endometrial cancer, abdominal obesity as a risk factor is associated with a
      chronic inflammatory process, confirmed by the increase of inflammatory markers.
      The study aimed to identify a correlation between abdominal obesity, plasma
      adipokine levels and endometrial cancer. MATERIAL AND METHOD: Two groups of
      patients were included in the study: group I - 44 patients diagnosed with
      endometrial cancer, group II - 44 patients without gynecological pathology or
      inflammatory disorders. After the performance of clinical examination and
      anthropometric measurements, abdominal fat was determined by dual X-ray
      absorptiometry and plasma adiponectin and leptin levels were measured. RESULTS: A
      significantly higher abdominal fat and leptin value was found in the group of
      patients in with endometrial cancer (p < 0.0001), while the plasma adiponectin
      level was significantly lower, compared to the control group (p < 0.0001).
      Abdominal fat was in a negative linear correlation with the plasma adiponectin
      level and in a positive linear correlation with the plasma leptin level.
      CONCLUSIONS: The measurement of adiponectin and leptin levels associated with the
      determination of abdominal adipose tissue can be a useful predictor factor for
      endometrial cancer.

PMID- 23544716
TI  - Overview of the epidemiology, diagnosis, and disease progression associated with
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system that affects approximately 400,000 people in the United
      States. The etiology of MS is unknown, but it is likely the result of a complex
      interaction between genetic and environmental factors and the immune system. The
      clinical manifestations of MS are highly variable, but most patients initially
      experience a relapsing-remitting course. Patients accumulate disability as a
      result of incomplete recovery from acute exacerbations and/or gradual disease
      progression. This article briefly reviews the immunopathology of MS, the symptoms
      and natural course of the disease, and the recently revised MS diagnostic
      criteria.

PMID- 23544717
TI  - A review of current and emerging therapeutic strategies in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic immune-mediated disease that potentially
      requires symptomatic and disease-modifying therapies. Numerous symptoms (eg,
      fatigue, spasticity, depression, bowel and bladder dysfunction, pain, and
      impaired mobility) are associated with the neurologic damage that results from
      MS. Several therapies (eg, modafinil, dalfampridine, baclofen, diazepam,
      gabapentin, opioids) are used for symptomatic treatment of disability and
      symptoms, but these do not improve disease outcome. Intravenous corticosteroids
      (with or without an oral corticosteroid taper) are used in the management of MS
      exacerbations, but do not appear to affect the degree of improvement from acute
      exacerbations. A more definitive therapy for MS should reduce relapse rate,
      prolong remission, limit the onset of new MS lesions, and postpone the
      development of long-term disability. The currently available MS disease-modifying
      therapies have been shown to reduce relapse rate, have beneficial effects on
      magnetic resonance imaging measures, and delay accumulation of disability. In
      addition, a number of agents are in development, but thus far no beneficial agent
      has been established in primary-progressive MS.

PMID- 23544718
TI  - Managed care aspects of managing multiple sclerosis.
AB  - Multiple sclerosis (MS) is associated with significant direct and indirect costs.
      Pharmacoeconomic studies of MS therapies have generally shown results which were
      not considered to be cost-effective when incremental cost-effectiveness ratios
      were analyzed for quality-adjusted life-years. When prevented relapses were
      considered as an end point, the cost-effectiveness results were generally more
      favorable, although the studies analyzed were limited by assumptions, projected
      outcomes, and lack of data on adverse events. Managed care professionals and
      clinicians can ensure maximized effectiveness of therapy by supporting adherence
      and by providing disease therapy management programs. Specialty pharmacies are an
      effective way to control costs and optimize the involvement of patients in their
      care.

PMID- 23544719
TI  - [SEMERGEN XXXIV National Conference - the chronic patient: our responsibility].

PMID- 23544720
TI  - [Prevalence of neuropathic pain according to the NP4 test in primary care].
AB  - BACKGROUND: Primary Care Physicians are usually the first to see patients with
      neuropathic pain. The aim of this study is to assess the prevalence of
      neuropathic pain, its therapeutic management, and to clinically characterize
      these patients. MATERIAL AND METHODS: An epidemiological, observational, cross
      sectional study was carried out in Spanish Primary Care settings. The first 25
      patients older than 18 years with any type of pain (a total of 16,115) were
      registered, and the first 5 with a high neuropathic pain component according to
      the NP4 test, and was clinically confirmed (n= 3,836) were included in the study.
      Pain intensity and impact on daily activities, as well as overall satisfaction
      with treatment were assessed. RESULTS: A total of 45.7% of patients had
      neuropathic pain according to NP4 test. The median age was 59 years, and 60% were
      women. Patients took a mean of 2.4 drugs, with NSAIDs (53%) and non-opioid
      analgesics (51%) being the most common. The scores for Pain intensity and
      interference in daily activities were both 6.2. The overall opinion of the SATMED
      Q test was 47.3/100, which was 1.4 points lower than the standardised score
      according to Spanish population. CONCLUSIONS: Neuropathic pain according to NP4
      test is highly prevalent in Spanish Primary Care settings. The management of
      these patients with NSAIDs and non-opioid analgesics is not appropriate, as they
      are not recommended for this kind of pain. Although they were being treated with
      more than 2 analgesics, they still referred to high pain intensity, interference
      in daily activities, and a low general opinion of the treatment.

PMID- 23544721
TI  - [Madelung's disease].
AB  - Madelung's disease or Benign Symmetric Lipomatosis is a rare disease
      characterised by masses of adipose tissue spread symmetrically along the neck,
      trunk, shoulders and upper arms. It affects men from 30 to 60 years old with a
      previous history of alcoholism. Surgery is the only effective treatment.

PMID- 23544722
TI  - [Telephone interruptions in family doctor clinics in two health centres in
      Saragossa].
AB  - OBJECTIVES: To analyse disruptions due to telephone calls in primary care
      clinics, their reasons and distribution during the working day. DESIGN: Cross
      sectional descriptive study. SETTING: The study was conducted in primary care, 2
      urban Primary Care Health Centres in Area II of Zaragoza. METHODOLOGY: Seven
      primary care physicians recorded all calls, whether or not they were passed on
      from the admissions service to clinics, their origin and characteristics, over a
      period of 5.5 months. RESULTS: The overall mean percentage of calls per day for
      each doctor was of 1.39 (SD 1.5), being 1.66 (SD 1.53) in San Jose Norte and 1.22
      (SD 1.46) in San Jose Centro (P=.012), with a difference between 0.2 and 0.68
      calls per day per clinic. The mean number of calls per day in the morning clinics
      and per clinic was 1.37 (SD 1.53) and 1.44 (SD 1.41) in the afternoon clinics,
      there being a significant difference (P=. 62). Calls originated by the patients
      themselves to speak directly with their doctors are more frequent in the morning
      than afternoon hours (28.5% and 26.5%). The distribution of calls is mainly from
      the 10.30 to 1 p.m., and between the 17:00 and 18:00 hours. CONCLUSIONS:
      Quantifying the telephone calls that occur during the family physician clinics,
      as well as determining their distribution and reasons, allows strategies to be
      developed to take advantage of the phone calls, as well as minimising disruption
      in the clinics.

PMID- 23544723
TI  - [Pharmacological cost impact of the osteoarthritis of the knee in a primary care
      health centre].
AB  - OBJECTIVE: To establish the pharmacological cost incurred by an urban Primary
      Health Care centre for treating osteoarthritis (OA) of the knee, including the
      main drugs used in its treatment and its contribution to the total cost of each
      group studied. PATIENTS AND METHODS: A cross-sectional, descriptive study of 188
      patients diagnosed with OA of the knee. After counting the total number of pre
      packaged pharmaceutical products assigned to each patient over one year, the
      average cost of each product was calculated. The ratio between the total cost and
      the total number of patients was then calculated, which gave the cost per patient
      per year. RESULTS: NSAIDs (non-steroids anti-inflammatory drugs) were the most
      frequently prescribed. SYSADOAs (symptomatic slow-acting drugs for
      osteoarthritis) rated second in both frequency and cost. Acetaminophen rated
      third. Topical treatments, "other analgesics" and proton pump inhibitors (PPIs),
      cost much less. The total pharmacological cost per patient per year thus amounted
      to 151.6 ? (SD:+/-101,9). CONCLUSIONS: The pharmacological cost for treatment of
      osteoarthritis of the knee incurs an increase in cost of health resources in
      Primary Care. The total pharmacological cost per patient per year was 151.60 ?.
      In our centre, NSAIDs account for most of the pharmacological costs in the
      treatment of osteoarthritis of the knee.

PMID- 23544724
TI  - [An update on vaccines. Theory, realities and myths (and II) update in the
      Spanish vaccine schedule].
AB  - The criteria for modifying the immunization schedule depends on the disease
      (load, frequency, morbidity and mortality, killing potential) of the vaccine
      (immunogenicity, efficacy, effectiveness, efficiency, compatibility, safety and
      assurance of supply) and society (impact on the population and the health system,
      perception of disease in the population). In Spain there are 19 different vaccine
      schedules that are not justified from a health, epidemiological, social or
      economic perspective. The Spanish Association of Paediatrics recommends:
      vaccinating against rotavirus from the sixth week, against papillomavirus in
      preadolescent girls, achieving universal pneumococcal protection, administering a
      second dose of varicella at 3-4 years, changing the indications of the pertussis
      vaccine and flu vaccine and hepatitis A risk. We will review further the vaccines
      that have recently been introduced: rotavirus, pneumococcus and papillomavirus
      and mention the major changes in existing ones.

PMID- 23544725
TI  - [Therapeutic approach to insomnia].
AB  - Insomnia is the inability to reconcile or maintain sleep or the feeling of not
      having a good night's sleep, resulting in daytime dysfunction. It affects health
      and the quality of life of patients who suffer from it. However, up to 10% of
      insomniac patients do not receive an adequate treatment. Insomnia requires an
      integrated approach, treating the causes or triggers and symptoms, and assessing
      their impact on the patient. Treatment must be based on strategies of changing
      behaviour and changes in lifestyle that are associated, and when deemed
      necessary, pharmacological treatment. The main hypnotics are benzodiazepines and
      Z drugs or non-benzodiazepine hypnotics, on not finding any evidence of
      clinically significant differences between the use of one or the other. Both
      therapeutic groups are effective in the treatment of insomnia in the short term,
      but there is no evidence on their long-term effectiveness.

PMID- 23544726
TI  - [Rapid headache guidelines. Neurology consensus between Neurology (SAN) and
      Primary Care (SEMERGEN Andalucia). Referral criteria].
AB  - Headache is one of the most frequent reasons for consultation in our health
      centers, something which should not be surprising if we consider that is one of
      the most common symptoms experienced by the population. The main concern of the
      family physician and emergency physician is to reach a correct diagnosis by
      clinical history and a basic neurological examination and adapted to the time and
      means at its disposal. In case of diagnostic doubts or suspected secondary
      headache, the primary care physician or emergency medical have to refer the
      patient to be studied and/or treated for Neurology services, such referral shall
      be made with varying degrees of urgency depending on the presence, or not, of
      symptoms or signs of alarm. A working group consisting of Neurologists of
      Sociedad Andaluza de Neurologia (SAN) to provide services in different hospitals
      in Andalucia and Family Physicians representatives of the Sociedad Andaluza de
      Medicina Familiar y Comunitaria (SAMFyC) and the Sociedad Espanola de Medicos de
      Atencion Primaria (SEMERGEN Andalucia), has developed a Quick Guide headache,
      which addresses the more practical aspects for the diagnosis, treatment and
      monitoring of patients with headache. We show you in this paper, the chapter that
      deals the alarm criteria and referral.

PMID- 23544727
TI  - [Stevens-Johnson syndrome: presentation of a case of fever and a rash].
AB  - Stevens-Johnson syndrome is a rare acute process with a mortality rate of 20%.
      Stevens-Johnson syndrome is a reactive dermatosis consisting of an erythema
      multiforme with the presence of vesicles and or blisters in the mucosa
      (particularly oral). Its more severe presentation is toxic epidermal necrolysis.
      The most frequent cause is hypersensitivity to multiple drugs, followed by
      infections, connective tissue diseases, and neoplasms. Although it is a rare
      syndrome, we must consider it, as the rapid installation of an appropriate
      treatment, as well as the rapid withdrawal of the triggering drug, can
      considerably reduce the morbidity and mortality.

PMID- 23544728
TI  - [Malaise in an elderly woman: presentation of a case].
AB  - We report on an elderly patient who came to the clinic due to general malaise.
      The complicated progress and gradual worsening led us to conduct a deeper study
      of the status of the patient, finding a liver abscess that could be
      satisfactorily treated.

PMID- 23544729
TI  - [Low back pain with a "detachable balloons" image in a simple chest X-ray].
AB  - The "detachable balloons" image in simple chest-X-ray is not very common in
      Primary Care. We present the case of patient who consulted for uncomplicated low
      back pain. The spine X-ray was suggestive of arthrosis. A blood analysis was
      requested within the Preventive Activities Programme, which showed moderate
      anaemia. The patient was referred to the Hospital where a probable renal cell
      carcinoma was detected in the thoraco-abdominal Computed Axial Tomography.
      Finally, the initial symptom (low back pain) was due to bone metastasis, but
      further information was required to continue with the diagnostic process. The
      anaemia and the "detachable balloons" image were key factors in the final
      diagnosis.

PMID- 23544730
TI  - [A mortal cause of syncope].
AB  - Anaphylaxis is a generalized reaction produced by the massive release of
      mediators from mast cells, is rapid in onset and may cause death. The diagnosis
      is clinical, and the initial symptoms often overlap with those of many other
      disorders such as, vasovagal reactions, anxiety or asthma, and is often
      underdiagnosed. A high index of suspicion is necessary for the diagnosis. We
      report the case of a young woman who presented with syncope in a Primary Care
      Centre. In spite of the absence of skin lesions, we suspected an anaphylaxis
      because of the refractory low blood pressure. Thus treatment was started she was
      transferred to the Hospital. In the Emergency Department, the elevated serum
      tryptase levels supported our diagnosis. The absence of a clear exposure to a
      known allergen lead us to suspect a hydatid cysts rupture. The abdominal
      ultrasound and CT scan confirmed this.

PMID- 23544731
TI  - [A 45 year-old male with lumbar tumours].
AB  - A 45 year old Filipino male, with history of Hepatitis B virus infection, was
      seen in his primary care clinic with a lumbar mass for the past three months. On
      physical examination the lower limbs showed decrease strength, chest X-rays
      showed bilateral thickening of the apical pleura, the Mantoux skin test was
      positive and a lumbar magnetic resonance imaging study showed a compression
      fracture of D4 vertebral body and soft-tissue abscess in L1. Microbiological
      examination was positive for M. tuberculosis complex, and with the diagnosis of
      Potts disease, he began treatment. With the advent of anti-tuberculosis drugs,
      spinal involvement of tuberculosis is rare, but it continues to have a high
      impact on morbidity. Treatment of vertebral involvement is based on anti
      tuberculosis drugs and surgery.

PMID- 23544732
TI  - Centennial of the description of Hashimoto's thyroiditis: two thought-provoking
      events.

PMID- 23544733
TI  - Solid/liquid phase diagram of the ammonium sulfate/glutaric acid/water system.
AB  - We have studied the low temperature phase diagram and water activities of the
      ammonium sulfate/glutaric acid/water system using differential scanning
      calorimetry, infrared spectroscopy of thin films, and a new technique:
      differential scanning calorimetry-video microscopy. Using these techniques, we
      have determined that there is a temperature-dependent kinetic effect to the
      dissolution of glutaric acid in aqueous solution. We have mapped the solid/liquid
      ternary phase diagram, determined the water activities based on the freezing
      point depression, and determined the ice/glutaric acid phase boundary as well as
      the ternary eutectic composition and temperature. We have also modified our
      glutaric acid/water binary phase diagram previously published based on these new
      results. We compare our results for the ternary system to the predictions of the
      Extended AIM Aerosol Thermodynamics Model (E-AIM), and find good agreement for
      the ice melting points in the ice primary phase field of this system; however,
      significant differences were found with respect to phase boundaries,
      concentration and temperature of the ternary eutectic, and glutaric acid
      dissolution.

PMID- 23544738
TI  - Development of a large scale asymmetric synthesis of the glucocorticoid agonist
      BI 653048 BS H3PO4.
AB  - The development of a large scale synthesis of the glucocorticoid agonist BI
      653048 BS H3PO4 (1.H3PO4) is presented. A key trifluoromethyl ketone intermediate
      22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by an
      enolization/bromine-magnesium exchange/electrophile trapping reaction. A
      nonselective propargylation of trifluoromethyl ketone 22 gave the desired
      diastereomer in 32% yield and with dr = 98:2 from a 1:1 diastereomeric mixture
      after crystallization. Subsequently, an asymmetric propargylation was developed
      which provided the desired diastereomer in 4:1 diastereoselectivity and 75% yield
      with dr = 99:1 after crystallization. The azaindole moiety was efficiently
      installed by a one-pot cross coupling/indolization reaction. An efficient
      deprotection of the 4-methoxyphenethyl group was developed using H3PO4/anisole to
      produce the anisole solvate of the API in high yield and purity. The final form,
      a phosphoric acid cocrystal, was produced in high yield and purity and with
      consistent control of particle size.

PMID- 23544739
TI  - Management of incidental and non-incidental papillary thyroid microcarcinoma.
AB  - BACKGROUND: The incidence of papillary thyroid cancer is rising, with an increase
      in the number of microcarcinomas being discovered. There is controversy in the
      literature regarding the optimal management of these tumours. This study aimed to
      review our institution's experience with the presentation and management of
      papillary thyroid microcarcinoma. METHODS: Retrospective analysis from the Sydney
      Head and Neck Cancer Institute, from 1987 to 2009. RESULTS: A total of 228
      patients were analysed. Papillary thyroid microcarcinomas were discovered
      incidentally in 116 (50.9 per cent) patients and non-incidentally in the
      remaining 112 (49.1 per cent) patients. Amongst the non-incidental group, 11.6
      per cent of patients presented with lateral cervical lymph node involvement. Non
      incidental microcarcinomas were significantly associated with younger age (<45
      years) (p = 0.007) and larger tumours (5-10 mm) (p < 0.001). Only four patients
      in the incidental group suffered recurrent disease (locoregional). No patient
      developed distant metastatic disease or died during follow up. CONCLUSION:
      Papillary thyroid microcarcinomas present both incidentally and non-incidentally,
      with equal prevalence. Non-incidental tumours not infrequently present with
      cervical lymph node disease. The patient outcome is generally excellent.

PMID- 23544740
TI  - Lack of relationship between birth conditions and allergic disorders in Japanese
      children aged 3 years.
AB  - BACKGROUND: The current cross-sectional study examined the associations between
      low birth weight (LBW), preterm birth, and small-for-gestational-age (SGA) and
      the prevalence of wheeze, asthma, and eczema in Japanese children aged 3 years.
      METHODS: Study subjects were 2004 children. All data were obtained using a
      questionnaire. Outcomes were defined according to the criteria of the
      International Study of Asthma and Allergies in Childhood. Adjustment was made for
      sex, number of siblings, breastfeeding duration, paternal and maternal
      educational level, paternal and maternal history of allergic disorders, maternal
      smoking during pregnancy, secondhand smoke exposure at home, and gestational age
      at birth. RESULTS: The prevalence of wheeze, asthma, and eczema in the previous
      12 months were 22.1%, 9.0%, and 17.5%, respectively, and 8.4% were classified as
      LBW (<2500 g), 4.7% as preterm birth (<37 weeks), and 7.1% as SGA (<10th
      percentile). There were no significant associations between LBW, preterm birth,
      or SGA and the prevalence of wheeze, asthma, or eczema. A positive relationship
      between preterm birth and asthma was of borderline significance in children whose
      mothers had smoked during pregnancy (adjusted OR: 4.71 [95% CI: 0.97-21.39]), but
      not in those whose mothers had never smoked during pregnancy; the multiplicative
      interaction between preterm birth and maternal smoking during pregnancy with
      respect to asthma was significant (p = .04). CONCLUSIONS: The current study
      failed to detect significant associations between birth conditions and allergic
      disorders. Nevertheless, we did find evidence for an interaction between preterm
      birth and maternal smoking during pregnancy affecting asthma.

PMID- 23544742
TI  - Enhanced room temperature magnetoresistance and spin injection from metallic
      cobalt in Co/ZnO and Co/ZnAlO films.
AB  - Co/ZnO and Co/ZnAlO films were prepared by depositing ultrathin cobalt layers and
      semiconductor layers on glass substrates at room temperature. The films consist
      of metallic Co particles, semiconductor matrix, and an interfacial magnetic
      semiconductor with the substitution of Co(2+) for Zn(2+) in the ZnO lattice at
      the interface between Co particles and the semiconductor matrix. Large room
      temperature negative tunneling magnetoresistance was observed in the films. In
      addition, the magnetism and magnetoresistance were obviously enhanced by adding
      aluminum to the ZnO, and in one Co/ZnAlO sample, the room temperature negative
      magnetoresistance value reaches -12.3% at 18 kOe (compared with -8.4% of the
      corresponding Co/ZnO film) and the spin polarization of the tunneling electrons
      is about 37.5% which is characteristic of metallic Co. This enhancement of the
      tunneling spin polarization has been ascribed to the tunneling through an
      interfacial magnetic semiconductor, which causes the robust spin injection from
      cobalt metal into the semiconductors at room temperature resulting from the spin
      filter effect of the interfacial magnetic semiconductors.

PMID- 23544741
TI  - Evaluation of selected angiogenic and inflammatory markers in endometriosis
      before and after danazol treatment.
AB  - Angiogenesis and inflammation are pivotal processes in developing endometriosis
      in the peritoneal cavity. The aim of the present study was to evaluate these two
      processes in women with endometriosis who had been treated with danazol to
      determine the sensitivity of a non-invasive test in diagnosing endometriosis. The
      clinical follow-up study was conducted in a group of 103 women diagnosed
      laparoscopically with endometriosis. Thirty-five patients qualified for danazol
      treatment. Pain was assessed using a visual analogue scale, whereas endometriosis
      was assessed using the revised American Society of Reproductive Medicine (rASRM)
      scale. Cancer antigen (CA)-125 and C-reactive protein (CRP) concentrations in
      plasma and peritoneal fluid were determined by immunoenzymatic methods, whereas
      vascular endothelial growth factor (VEGF) and interleukin (IL)-1beta
      concentrations in plasma and peritoneal fluid were determined by ELISA.
      Endometrial expression of IL-8 and platelet-derived growth factor alpha
      polypeptide (PDGF-A) was determined using real-time polymerase chain reaction
      (PCR). Women with endometriosis (68.9% of patients) had higher plasma
      concentrations of CA-125, as well as higher concentrations of both CA-125 and
      VEGF in the peritoneal fluid. Endometrial expression of IL-8 mRNA was
      significantly higher, whereas that of PDGF-A was significantly lower, in
      contrast. After danazol treatment the patients reported lower pain scores; in
      addition, CA-125 concentrations in the plasma were decreased (P<0.001), whereas
      VEGF concentration in the plasma increased (P=0.009). For the diagnosis of
      endometriosis, none of the combinations of given markers had a sensitivity >60%.
      Danazol treatment is highly effective in relieving pain and decreasing CA-125
      concentrations in the plasma. Higher plasma concentrations of VEGF after
      treatment could imply stimulation of angiogenesis. 

PMID- 23544743
TI  - Strategically placing green infrastructure: cost-effective land conservation in
      the floodplain.
AB  - Green infrastructure approaches have attracted increased attention from local
      governments as a way to lower flood risk and provide an array of other
      environmental services. The peer-reviewed literature, however, offers few
      estimates of the economic impacts of such approaches at the watershed scale. We
      estimate the avoided flood damages and the costs of preventing development of
      floodplain parcels in the East River Watershed of Wisconsin's Lower Fox River
      Basin. Results suggest that the costs of preventing conversion of all projected
      floodplain development would exceed the flood damage mitigation benefits by a
      substantial margin. However, targeting of investments to high-benefit, low-cost
      parcels can reverse this equation, generating net benefits. The analysis
      demonstrates how any flood-prone community can use a geographic-information-based
      model to estimate the flood damage reduction benefits of green infrastructure,
      compare them to the costs, and target investments to design cost-effective
      nonstructural flood damage mitigation policies.

PMID- 23544744
TI  - Genetic differentiation of Trachurus japonicus from the Northwestern Pacific
      based on the mitochondrial DNA control region.
AB  - Trachurus japonicus is a pelagic fish widely distributed from China, Korea to
      Japan. To examine the gene flow of T. japonicus between Chinese and Japanese
      coastal waters, eight populations were collected for the present study. Eighty
      seven variable sites defined 168 haplotypes. The populations of T. japonicus
      showed high haplotype diversity (h) with a range from 0.964 +/- 0.027 to 1.000 +/
      0.016 and low nucleotide diversity with a range from 0.011 +/- 0.006 to 0.015 +/
      0.008. The topology of the neighbour-joining tree showed no significant
      genealogical branches or clusters corresponding to sampling localities. The
      starburst structure of the minimum spanning tree suggested a very recent origin
      for most haplotypes. Both pairwise F st and analysis of molecular variance
      revealed no significant genetic differentiation throughout the range examined.
      The results of neutrality tests and mismatch distributions indicated that T.
      japonicus may experience a recent population demographic expansion.

PMID- 23544746
TI  - Glial proteins and peptides: implications in neuroinflammation.

PMID- 23544747
TI  - Neuron-microglia interaction in neuroinflammation.
AB  - Microglia are monocyte-macrophage lineage cells, while other glial cells are
      neuroectodermal origin. Accumulation of microglia is commonly observed around
      degenerating neurons. There, microglia produce a variety of factors and function
      both neurotoxic and neuroprotective. Thus, accumulation of glia in various
      neurological disorders is not a static scar, gliosis, but more actively involved
      in degeneration and regeneration as neuroinflammation. We have shown previously
      that the most neurotoxic factor from activated microglia is glutamate, and that
      the suppression of glutamate release from microglia results in amelioration of
      disease progression in animal models of neurodegenerative disorders. On the other
      hands, when exposed to harmful stimuli, neurons also produce various factors as
      "help me" signals. Recently, we found that a CX3C chemokine, fractalkine (FKN),
      and interleukin-34 (IL-34) were secreted from damaged neurons. FKN and IL-34
      differently activated microglia to rescue neurons by upregulating phagocytosis of
      toxicants or damaged debris, and production of anti-oxidant enzyme. The bi
      directional interaction between neurons and microglia is important for
      understanding of chronic neuroinflammation, and gives us clues for future
      therapeutic strategy against neurodegenerative disorders.

PMID- 23544748
TI  - Self-assembling peptide nanofibrous scaffolds for tissue engineering: novel
      approaches and strategies for effective functional regeneration.
AB  - Tissue engineering requires an ideal scaffold that will aid in the regeneration
      of the damaged tissues both structurally and functionally. Conventionally,
      polymeric nanofibrous scaffolds have been extensively used due to their
      structural similarity to the native extracellular matrix. Thus far, top-down
      approaches like electrospinning and phase separation have been predominantly used
      for the nanofiber fabrication. Recently, self-assembling peptide nanofibers
      (SAPNF) have been identified as promising scaffolds for tissue engineering
      applications. Molecular self-assembly of peptides, which is a bottom-up approach
      has laid foundations for the development of such novel scaffolds. Designer self
      assembling peptides provide functional support as well as bio-recognition due to
      the presence of bioactive motifs embedded in them. However, there are certain
      limitations to both electrospun and SAPNF scaffolds in terms of synthesis, cues
      presented to the biological system and applications. Design of composite, hybrid
      scaffolds by super-positioning possible cues may result in effective functional
      tissue regeneration at multiple levels.

PMID- 23544749
TI  - Quantitative analysis of the human AKR family members in cancer cell lines using
      the mTRAQ/MRM approach.
AB  - Members of human aldo-keto reductase (AKR) superfamily have been reported to be
      involved in cancer progression, whereas the final conclusion is not generally
      accepted. Herein, we propose a quantitative method to measure human AKR proteins
      in cells using mTRAQ-based multiple reaction monitoring (MRM). AKR peptides with
      multiple transitions were carefully selected upon tryptic digestion of the
      recombinant AKR proteins, while AKR proteins were identified by SDS-PAGE
      fractionation coupled with LC-MS/MS. Utilizing mTRAQ triplex labeling to produce
      the derivative peptides, calibration curves were generated using the mixed lysate
      as background, and no significantly different quantification of AKRs was elicited
      from the two sets of calibration curves under the mixed and single lysate as
      background. We employed this approach to quantitatively determine the 6 AKR
      proteins, AKR1A1, AKR1B1, AKR1B10, AKR1C1/C2, AKR1C3, and AKR1C4, in 7 different
      cancer cell lines and for the first time to obtain the absolute quantities of all
      the AKR proteins in each cell. The cluster plot revealed that AKR1A and AKR1B
      were widely distributed in most cancer cells with relatively stable abundances,
      whereas AKR1Cs were unevenly detected among these cells with diverse dynamic
      abundances. The AKR quantitative distribution in different cancer cells,
      therefore, may assist further exploration toward how the AKR proteins are
      involved in tumorigenesis.

PMID- 23544750
TI  - Counterion-mediated hierarchical self-assembly of an ABC miktoarm star
      terpolymer.
AB  - Directed self-assembly processes of polymeric systems represent a powerful
      approach for the generation of structural hierarchy in analogy to biological
      systems. Herein, we utilize triiodide as a strongly polarizable counterion to
      induce hierarchical self-assembly of an ABC miktoarm star terpolymer comprising a
      polybutadiene (PB), a poly(tert-butyl methacrylate) (PtBMA), and a poly(N-methyl
      2-vinylpyridinium) (P2VPq) segment. Hereby, the miktoarm architecture in
      conjunction with an increasing ratio of triiodide versus iodide counterions
      allows for a stepwise assembly of spherical micelles as initial building blocks
      into cylindrical structures and superstructures thereof. Finally, micrometer
      sized multicompartment particles with a periodic lamellar fine structure are
      observed, for which we introduce the term "woodlouse". The counterion-mediated
      decrease in hydrophilicity of the corona-forming P2VPq block is the underlying
      trigger to induce this hierarchical structure formation. All individual steps and
      the corresponding intermediates toward these well-defined superstructures were
      intensively studied by scattering and electron microscopic techniques, including
      transmission electron microtomography.

PMID- 23544753
TI  - Communication patterns within a group of shelter dogs and implications for their
      welfare.
AB  - Keeping shelter dogs in groups provides them with a more socially and physically
      enriched environment, but eventually it may cause them stress. Understanding
      dogs' communication could help shelter staff recognize and prevent undesirable
      communicative patterns and encourage desirable ones. Therefore, the objective of
      this study was to determine communication patterns in a group of dogs in a
      shelter. The observed dogs were engaged in different classes of dyadic and group
      interactions. Certain dogs were frequently initiators of dyadic interactions, and
      different dogs were the recipients. The predominant form of dyadic interactions
      was a neutral one, and aggressive behavior was rarely observed. The tendency of
      certain dogs to interact continuously may represent a nuisance for less social
      individuals. All of the dogs participated in 3 defined classes of group
      interactions. At the group level, the dogs frequently interact vocally or
      olfactorily. A major welfare problem may be very vocal dogs because their
      vocalizations are noisy and broadcast far-reaching signals. The frequency of some
      group interactions was reduced by the amount of time the dogs had in the shelter.

PMID- 23544752
TI  - Efficient cooperative restraint training with rhesus macaques.
AB  - It is sometimes necessary for nonhuman primates to be restrained during
      biomedical and psychosocial research. Such restraint is often accomplished using
      a "primate chair." This article details a method for training adult rhesus
      macaques to cooperate with a chair restraint procedure using positive and
      negative reinforcement. Successful training was accomplished rapidly in
      approximately 14 training days. The success of this training technique suggests
      that this method represents a refinement to traditional techniques. Further, this
      method worked effectively for animals previously deemed unfit for traditional
      pole-and-collar training.

PMID- 23544754
TI  - Effect of breed, cage type, and reproductive phase on fecal corticosterone levels
      in doe rabbits.
AB  - Fecal corticosterone concentration (FCC) is increasingly being used as a
      noninvasive indicator of stress in assessment of nonhuman animal welfare. The aim
      of this study was to evaluate effects of breed, cage type, reproductive phase,
      and their interactions on FCC levels in doe rabbits. A total of 252 doe rabbits
      were randomly assigned to 2 groups. Does were individually housed in either
      standard dimension cages (SC) or in cages with a volume more than double that of
      the SC. Bigger cages (BC) were equipped with a plastic foot mat. Breed, cage
      type, and reproductive phase significantly affected FCC. New Zealand hybrids
      showed higher FCCs (p < .001) when compared with the autochthonous breed (27.77
      +/- 0.47 vs. 24.61 +/- 0.36 pg g(-1), respectively). Increased cage size coupled
      with a plastic foot mat resulted in a significant decrease in doe FCC. The
      highest FCCs were detected at partum (BC: 30.40 +/- 0.81 pg g(-1); SC: 33.36 +/-
      0.86 pg g(-1); p <= .05), followed by postweaning (BC: 25.09 +/- 0.95 pg g(-1);
      SC: 27.63 +/- 0.95 pg g(-1); p <= .05). These results support the hypothesis that
      measurement of FCC provides a useful indicator of chronic stress in doe rabbits.

PMID- 23544755
TI  - The welfare and productivity of dry sows in different group housing systems in
      New Zealand.
AB  - This research aimed to evaluate sow welfare and identify potential welfare
      compromise in specific group housing systems for sows in New Zealand. The
      relationship between overall welfare outcome on-farm and sow productivity was
      also investigated. Twenty commercial farms were chosen to represent the spectrum
      of layouts and management practices of New Zealand pork producers. During a farm
      visit, housing, management, behavior, welfare, and productivity data were
      collected. The following criteria were used to describe each farm: group size,
      the duration of time in a gestation stall, presence of bedding, feeding method,
      and feeding frequency. Sows in medium groups had the most piglets born alive per
      litter (13.14 piglets). Sows fed twice daily had significantly higher
      stereotypies than sows fed at a different frequency. A welfare index (WI; minimum
      possible WI = 0.33, maximum possible WI = 5.0) was calculated for each farm and
      accounted for the following parameters: injuries, lameness, stereotypies, coat
      condition, and soiling. The mean WI was 0.65 (+/- 0.14 SD). A low WI represented
      fewer indicators that were associated with compromised welfare. Thus, existing
      group housing systems are being managed effectively to achieve good standards of
      sow welfare.

PMID- 23544756
TI  - Owner attachment and problem behaviors related to relinquishment and training
      techniques of dogs.
AB  - Problematic behaviors are a significant reason for relinquishment, and
      relinquished dogs are more likely to have problem behaviors. This study utilized
      standardized surveys of owners (companion animal guardians) relinquishing their
      dogs to shelters and dog owners visiting vaccination clinics. "Relinquishing" and
      "continuing" owners were asked questions in the following categories: demographic
      information, training methods and tools, frequencies in which their dogs engaged
      in problematic behaviors, and attachment to their dogs. "Relinquishers" were also
      asked to provide their reasons for relinquishment. The results of 129 surveys (80
      relinquishing and 49 continuing) showed that relinquishers scored lower on
      companion animal attachment than continuing owners. Pit bull-type dogs were
      represented more in the relinquishing group. Relinquished dogs were no less
      likely to have attended training classes than continuing dogs. In both groups,
      owners who used punishment-based collars reported less satisfaction with their
      dogs' overall and leash-walking behaviors. Pit bull-type dogs were reported to be
      no less well behaved compared with all other breeds combined. Sixty-five percent
      of relinquishers reported some behavioral reason for relinquishment. Forty-eight
      percent of relinquishers indicated that at least 1 problem behavior was a strong
      influence on their decision to relinquish.

PMID- 23544757
TI  - A veterinary and behavioral analysis of dolphin killing methods currently used in
      the "drive hunt" in Taiji, Japan.
AB  - Annually in Japanese waters, small cetaceans are killed in "drive hunts" with
      quotas set by the government of Japan. The Taiji Fishing Cooperative in Japan has
      published the details of a new killing method that involves cutting (transecting)
      the spinal cord and purports to reduce time to death. The method involves the
      repeated insertion of a metal rod followed by the plugging of the wound to
      prevent blood loss into the water. To date, a paucity of data exists regarding
      these methods utilized in the drive hunts. Our veterinary and behavioral analysis
      of video documentation of this method indicates that it does not immediately lead
      to death and that the time to death data provided in the description of the
      method, based on termination of breathing and movement, is not supported by the
      available video data. The method employed causes damage to the vertebral blood
      vessels and the vascular rete from insertion of the rod that will lead to
      significant hemorrhage, but this alone would not produce a rapid death in a large
      mammal of this type. The method induces paraplegia (paralysis of the body) and
      death through trauma and gradual blood loss. This killing method does not conform
      to the recognized requirement for "immediate insensibility" and would not be
      tolerated or permitted in any regulated slaughterhouse process in the developed
      world.

PMID- 23544760
TI  - Mental health in ACOs: missed opportunities and low-hanging fruit.

PMID- 23544761
TI  - Effectiveness and cost-effectiveness of diabetes prevention among adherent
      participants.
AB  - OBJECTIVES: We report the 10-year effectiveness and within-trial cost
      effectiveness of the Diabetes Prevention Program (DPP) and its Outcomes Study
      (DPPOS) interventions among participants who were adherent to the interventions.
      STUDY DESIGN: DPP was a 3-year randomized clinical trial followed by 7 years of
      open-label modified intervention follow-up. METHODS: Data on resource
      utilization, cost, and quality of life were collected prospectively. Economic
      analyses were performed from health system and societal perspectives. Lifestyle
      adherence was defined as achieving and maintaining a 5% reduction in initial body
      weight, and metformin adherence as taking metformin at 80% of study visits.
      RESULTS: The relative risk reduction was 49.4% among adherent lifestyle
      participants and 20.8% among adherent metformin participants compared with
      placebo. Over 10 years, the cumulative, undiscounted, per capita direct medical
      costs of the interventions, as implemented during the DPP, were greater for
      adherent lifestyle participants ($4810) than adherent metformin participants
      ($2934) or placebo ($768). Over 10 years, the cumulative, per capita non
      interventionrelated direct medical costs were $4250 greater for placebo
      participants compared with adherent lifestyle participants and $3251 greater
      compared with adherent metformin participants. The cumulative quality-adjusted
      life-years (QALYs) accrued over 10 years were greater for lifestyle (6.80) than
      metformin (6.74) or placebo (6.67). Without discounting, from a modified societal
      perspective (excluding participant time) and a full societal perspective
      (including participant time), lifestyle cost < $5000 per QALY-gained and
      metformin was cost saving compared with placebo. CONCLUSIONS: Over 10 years,
      lifestyle intervention and metformin were cost-effective or cost saving compared
      with placebo. These analyses confirm that lifestyle and metformin represent a
      good value for money.

PMID- 23544763
TI  - Measuring quality in the early years of health insurance exchanges.
AB  - OBJECTIVES: To identify quality measures that health plans can reliably report
      during the early years of health insurance exchanges and over time, and to
      suggest strategies to increase the availability of quality results to use in
      rating and monitoring plans. STUDY DESIGN: Projection of a set of measures
      available for public reporting based on prevalence and experience with health
      plans' reporting of the quality measures. METHODS: For the quality measures
      included in the federal Initial Core Set of Adult Health Care Quality Measures
      for Medicaid-Eligible Adults, we looked at the proportion of people in the United
      States who would be eligible for each measure, and if available, the number of
      plans that in the past were not able to report reliable Healthcare Effectiveness
      Data and Information Set results to the National Committee for Quality Assurance
      because of low membership. We developed estimates of each state's exchange
      enrollment, and used the number of plans currently accredited in the state to
      estimate how many plans will offer coverage to determine the average exchange
      plan membership per state in 2014 and 2018. RESULTS: In the early years exchange
      plans should be able to report a set of 14 preventive, chronic care, and access
      to-service measures. As health plan membership grows through the years, more
      measures, including behavioral health, can be phased in. CONCLUSIONS: In 2015 and
      2016, all exchanges should require plans to report the 14 measures and if needed,
      use suggested strategies to build the results for public reporting.

PMID- 23544762
TI  - Multilevel predictors of colorectal cancer screening use in California.
AB  - BACKGROUND: Screening can detect colorectal cancer (CRC) early, yet its uptake
      needs to be improved. Social determinants of health (SDOH) may be linked to CRC
      screening use but are not well understood. OBJECTIVES: To examine geographic
      variation in CRC screening and the extent to which multilevel SDOH explain its
      use in California, the most populous and racially/ethnically diverse state in the
      United States. STUDY DESIGN: Analysis of individual and neighborhood data on
      20,626 adult respondents aged >50 years from the 2005 California Health Interview
      Survey. METHODS: We used multilevel logistic regression models to estimate the
      effects of individual characteristics and area-level segregation, socioeconomic
      status (SES), and healthcare resources at 2 different geographic levels on CRC
      screening use. RESULTS: We confirmed that individual-level factors (eg,
      race/ethnicity, income, insurance) were strong predictors and found that area
      level healthcare resources were associated with CRC screening. Primary care
      shortage in the Medical Service Study Area was associated with CRC screening for
      any modality (odds ratio [OR] = 0.89; 95% confidence interval [CI], 0.80-1.00).
      County-level HMO penetration (OR = 1.85; 95% CI, 1.47-2.33) and primary care
      shortage (OR = 0.73; 95% CI, 0.53-0.99) were associated with CRC screening with
      flexible sigmoidoscopy. CONCLUSIONS: Contextual factors including locality,
      primary care resources, and HMO membership are important determinants of CRC
      screening uptake; SES and segregation did not explain variation in screening
      behavior. More studies of contextual factors and varying geographic scales are
      needed to further elucidate their impact on CRC screening uptake.

PMID- 23544764
TI  - Engaging providers in underserved areas to adopt electronic health records.
AB  - OBJECTIVES: To assess Regional Extension Centers' (RECs') health IT outreach and
      provider engagement efforts among primary care providers (PCPs) based in
      underserved areas. STUDY DESIGN: A retrospective assessment of REC program
      enrollment. METHODS: We computed REC program enrollment rates among PCPs for the
      entire United States and across census regions and compared enrollment in
      underserved areas relative to non-underserved areas. Measures of area-level
      underserved status included rural and health professional shortage area (HPSA)
      designations. RESULTS: Of the estimated 302,689 ambulatory PCPs practicing in the
      United States, 120,783 (39.9%) were enrolled in an REC. REC enrollment rates
      among PCPs were higher in large rural (47.3%) and small rural (56.1%) areas
      relative to urban (37.9%) areas. REC enrollment rates among PCPs were also higher
      for single-county HPSAs (51.9%) relative to non-HPSAs (40.0%), geographic HPSAs
      (41.7%), and population group HPSAs (38.6%). The Northeast region exhibited the
      highest REC enrollment rates overall and across categories of underserved status
      relative to all other census regions. CONCLUSIONS: The REC program serves as a
      unique opportunity to address the health information technology needs of PCPs
      working in underserved areas. Over the course of 2 years, the program has
      exceeded its goal of enrolling 100,000 priority primary care providers. Provider
      engagement is the first step in a 3-step process aimed at getting providers to
      adopt and become meaningful users of electronic health records. Significant work
      remains for the RECs to meet these objectives, and future research should
      evaluate the success of the REC program in meeting subsequent milestones.

PMID- 23544765
TI  - Drug adherence after price changes in a previously compliant population.

PMID- 23544766
TI  - Rates of guideline adherence among US community oncologists treating NSCLC.
AB  - OBJECTIVES: To evaluate chemotherapy regimen utilization in patients with non
      small cell lung cancer (NSCLC) treated in US community oncology practices, to
      examine the relationship between evidence-based guideline adherence and the
      follow-up monitoring period (FUMP) over 1.5 years, and to understand the relative
      costs of commonly administered chemotherapy regimens. STUDY DESIGN: Retrospective
      data analysis. METHODS: Using a large US medical oncology clinical database
      derived from a proprietary web-based drug dispensing technology, we identified
      adult patients with NSCLC who started adjuvant therapy for early-stage disease or
      first-line therapy for advanced and metastatic disease from July 1, 2009, through
      June 30, 2010. Adjuvant or first-line regimen utilization and the FUMP within 1.5
      years were analyzed with respect to national evidence-based guideline adherence.
      Costs for commonly administered regimens based on 2010 Medicare reimbursement
      were compared. RESULTS: A total of 3505 patient treatment regimens were included
      in this study. Rates of guideline adherence were 75.0% and 61.3% for the first
      line and the adjuvant treatment groups, respectively (P < .0001). Treatment with
      guidelinebased regimens correlated with a significantly longer FUMP in the first
      line treatment groupcompared with non-guideline-based regimens (P = .005).
      Regimen costs for the top 11 regimens in the adjuvant and first-line treatment
      settings varied greatly. Low-cost regimens were prescribed more commonly.
      CONCLUSIONS: Rates of guideline adherence were significantly higher in the first
      line than in the adjuvant NSCLC treatment group. First-line treatment with
      guideline-based regimens correlated with an extended FUMP for advanced NSCLC
      patients.

PMID- 23544767
TI  - Synthesis, crystal structure, and solid-state NMR investigations of heteronuclear
      zn/co coordination networks--a comparative study.
AB  - Synthesis and solid-state NMR characterization of two isomorphous series of zinc
      and cobalt coordination networks with 1,2,4-triazolyl benzoate ligands are
      reported. Both series consist of 3D diamondoid networks with four-fold
      interpenetration. Solid-state NMR identifies the metal coordination of the
      ligands, and assignment of all (1)H and (13)C shifts was enabled by the
      combination of (13)C editing, FSLG-HETCOR spectra, and 2D (1)H-(1)H back-to-back
      (BABA) spectra with results from NMR-CASTEP calculations. The incorporation of
      Co(2+) replacing Zn(2+) ions in the MOF over the full range of concentrations has
      significant influences on the NMR spectra. A uniform distribution of metal ions
      is documented based on the analysis of (1)H T1 relaxation time measurements.

PMID- 23544768
TI  - Seed-mediated growth of shape-controlled wurtzite CdSe nanocrystals: platelets,
      cubes, and rods.
AB  - Prior investigations into the synthesis of colloidal CdSe nanocrystals with a
      wurtzite crystal structure (wz-CdSe) have given rise to well-developed methods
      for producing particles with anisotropic shapes such as rods, tetrapods, and
      wires; however, the synthesis of other shapes has proved challenging. Here we
      present a seed-mediated approach for the growth of colloidal, shape-controlled wz
      CdSe nanoparticles with previously unobserved morphologies. The synthesis, which
      makes use of small (2-3 nm) wz-CdSe nanocrystals as nucleation sites for
      subsequent growth, can be tuned to selectively yield colloidal wz-CdSe nanocubes
      and hexagonal nanoplatelets in addition to nanorod and bullet-shaped particles.
      We thoroughly characterize the morphology and crystal structures of these new
      shapes, as well as discuss possible growth mechanisms in the context of control
      over surface chemistry and the nucleation stage.

PMID- 23544769
TI  - A California sea lion (Zalophus californianus) can keep the beat: motor
      entrainment to rhythmic auditory stimuli in a non vocal mimic.
AB  - Is the ability to entrain motor activity to a rhythmic auditory stimulus, that is
      "keep a beat," dependent on neural adaptations supporting vocal mimicry? That is
      the premise of the vocal learning and synchronization hypothesis, recently
      advanced to explain the basis of this behavior (A. Patel, 2006, Musical Rhythm,
      Linguistic Rhythm, and Human Evolution, Music Perception, 24, 99-104). Prior to
      the current study, only vocal mimics, including humans, cockatoos, and
      budgerigars, have been shown to be capable of motoric entrainment. Here we
      demonstrate that a less vocally flexible animal, a California sea lion (Zalophus
      californianus), can learn to entrain head bobbing to an auditory rhythm meeting
      three criteria: a behavioral response that does not reproduce the stimulus;
      performance transfer to a range of novel tempos; and entrainment to complex,
      musical stimuli. These findings show that the capacity for entrainment of
      movement to rhythmic sounds does not depend on a capacity for vocal mimicry, and
      may be more widespread in the animal kingdom than previously hypothesized.

PMID- 23544770
TI  - Delay choice versus delay maintenance: different measures of delayed
      gratification in capuchin monkeys (Cebus apella).
AB  - Delaying gratification involves 2 components: (1) delay choice (selecting a
      delayed reward over an immediate one) and (2) delay maintenance (sustaining the
      decision to delay gratification even if the immediate reward is available during
      the delay). Two tasks most commonly have explored these components in primates:
      the intertemporal choice task and the accumulation task. It is unclear whether
      these tasks provide equivalent measures of delay of gratification. Here, we
      compared the performance on the intertemporal choice task and the accumulation
      task of capuchin monkeys (Cebus apella) belonging to 2 study populations. We
      found only limited evidence of a significant correlation in performance.
      Consequently, in contrast to what is often assumed, our data provide only partial
      support for the hypothesis that these tasks provide equivalent measures of delay
      of gratification.

PMID- 23544771
TI  - Symptomatic amyloid goiters: report of five cases.
AB  - BACKGROUND: Massive amyloid deposition in the thyroid to the point of goiter
      formation is rare. Here we describe the clinical presentation and outcomes of
      five patients with amyloid goiter (radiographically confirmed goiter in the
      context of tissue-proven thyroid amyloidosis) encountered in the past 23 years at
      our institution. METHODS: Mayo Clinic archives were searched between 1987 and
      2010 for a diagnosis of "thyroid amyloidosis," "amyloid deposits," "amyloid
      deposition," or "liquid chromatography consistent with amyloid." Inclusion
      criteria were symptomatic thyromegaly; tissue confirmation of thyroid enlarged by
      amyloid deposits; and radiologic confirmation of thyroid enlargement. RESULTS:
      Five patients were identified who met all inclusion criteria. Amyloid goiter
      etiology included both primary and secondary amyloidosis, and the goiters ranged
      in weight from 50 to 130 g each. Diagnosis was made by fine-needle aspiration
      biopsy with Congo red staining and, if needed, spectrophotometry. All five
      patients had histories of persistent hoarseness for several years before
      presentation with compressive symptoms referable to their enlarging thyroids, and
      all had some degree of thyroid dysfunction (both hypothyroidism and
      hyperthyroidism) by the end of our follow-up period, which ranged from 5 months
      to 13 years. Two patients underwent surgical interventions, two were managed
      conservatively, and in one, the goiter shrank after systemic therapy for
      amyloidosis. CONCLUSIONS: Our clinical observations suggest slower goiter
      progression and a higher prevalence of thyroid dysfunction than previously
      thought.

PMID- 23544772
TI  - [Vaccination against the human papilloma virus: a commitment of everybody].

PMID- 23544773
TI  - [CASERIA program (Healthy Habits in Primary School Questionnaire). Responses of 6
      to 10 year-old children].
AB  - In schoolchildren examinations, carried out periodically, we detect a continuous
      increase in obesity and sedentarism in our schoolchildren. In this study we
      attempt to compare, with objective data, the real situation of the childhood
      population in our area, as regards their eating habits, physical activity and
      hygiene. MATERIAL AND METHODS: Questionnaires on eating habits, preferences as
      regards diet, doing exercise, and dental hygiene, were handed out to 430
      schoolchildren between 6 and 10 years-old. A total of 366 were valid for the
      study. RESULTS: The majority (85.8%) of those surveyed lived within a
      "traditional" family; 22% had family members who were overweight; 96.7% had
      breakfast before going to school, with milk products being the most consumed; the
      cake and pastry industry was well used, both at breakfast (7.4%) and at playtime
      (16.9%). The favourite food was pasta in 29.8% of cases, followed by potatoes,
      particularly fried (10.4%). The least liked foods were vegetables (26.2%) and
      fish (8.2%). Television was watched for more than 2 hours by 70%; 34% exceeded 2
      hours or more per day playing with video consoles or similar. On the other hand,
      homework and studying took up more than 2 hours daily for 50% of pupils. A
      majority (55%) of those surveyed ate sweets 2 or more time a day, and to eat and
      watch television at the same time was an almost constant habit in more than 60%.
      Of the participants in the study, 9.29% never brushed their teeth. CONCLUSIONS:
      The theoretical knowledge of what should be a correct diet seems adequate, but
      its putting into practice is not. The population studies had fairly sedentary
      habits, with little fruit and they did not like pulses or vegetables or fish. All
      these factors decrease the cardiovascular protection associated with its practice
      and consumption. We have shown that they are already present since childhood in
      our population, which without a doubt will have repercussions in their future
      health status and well-being, if it is not changed.

PMID- 23544774
TI  - [A cross-sectional study to assess cardiovascular risk in the children of parents
      with diabetes mellitus or arterial hypertension].
AB  - INTRODUCTION: Cardiovascular disease in adults is the first cause of death, and
      in adolescents under 15 years old, it is the third cause of death. The purpose of
      this study was to investigate which risk factors for cardiovascular disease have
      the children of parents with diabetes or hypertension. MATERIAL AND METHODS: In a
      cross-sectional study conducted in the Family Medicine Unit No. 80 in Morelia,
      Michoacan, Mexico, were included 156 patients with diabetes mellitus,
      hypertension and without diabetes or hypertension (10 years of disease
      progression), and a biological child (age 7-15 years) to form pairs. Three groups
      were formed: child-parent with Diabetes; child-parent with Hypertension and child
      parent without Diabetes or Hypertension. Medical history, body mass index, blood
      glucose, cholesterol, triglycerides, c-LDL, c-HDL and signs of metabolic syndrome
      were recorded. RESULTS: The frequency of signs of metabolic syndrome was higher
      in parents with Diabetes (28.8%), and in children of parents without either
      diabetes or hypertension (11.5%). In binomial children-parents with Diabetes,
      serum glucose (OR=4.50: 95% CI; 2.32-8.73, P<.0001) was the most important risk
      factor to develop cardiovascular disease; in binomial children-parents with
      Hypertension it was total cholesterol (OR=4.143: 95% CI; 1.996-8.60, P<.0001);
      and, in binomial children-parents without either Diabetes or Hypertension, the
      abdominal circumference (OR=3.429: 95% CI; 1.621-7.251, P<.0001) was the most
      important risk factor. CONCLUSIONS: We conclude that children of parents with or
      without diabetes mellitus or hypertension are at increased risk for developing
      cardiovascular disease. Longitudinal studies are required using non
      pharmacological and pharmacological strategies that will have an impact on the
      most important risk factors for preventing cardiovascular disease.

PMID- 23544775
TI  - [Residual symptoms in elderly patients with depression].
AB  - OBJECTIVES: To look for residual symptoms in patients older than 65 years
      diagnosed with depression, and to find out if there are more residual symptoms in
      relation to physical comorbidity and the number of visits made to a Primary Care
      Centre. METHODS: A descriptive, randomised and cross-sectional multicentre study,
      with a sample of patients attending 3 urban Health Primary Care Centres. Patients
      older than 65 years with a diagnosis of depression and who had received more than
      3 months treatment were selected. Data was collected by means of questionnaires
      during personal interviews, which included universal data, time of onset,
      treatment recurrence, comorbidity, and residual symptoms. The Yesavage
      questionnaire, EQ-5D and VAS were also used. RESULTS: Of 100 patients studied,
      99% had residual symptoms, with 22% with 4 symptoms (from 10 asked). The most
      frequent symptom was the sadness (68%), followed by pain (55%), and loss of
      energy (55%). CONCLUSIONS: The prevalence of depression found in our study was
      13.8%, and a 99% had at least one residual symptom. Patients who lived as a
      couple and men (who performed more recreational activities) had a lower number of
      residual symptoms. No relationship was found between comorbidity and frequent use
      of Primary Care Centres with a higher number of residuals symptoms. The majority
      of patients suffered chronic depression (> 2 years). Benzodiazepines only were
      used as treatment in 18% of the patients.

PMID- 23544776
TI  - [Pharmacological compliance in the treatment of arterial hypertension. A review
      of studies published between 1975 and 2011].
AB  - A systematic review was performed from published articles on compliance (PubMed),
      between 1975 and first of June 2011. Specifically those which measured medication
      adherence using indirect methods (RCS and/or MEMS-Medication Event Monitoring
      System) were searched. Descriptors used were: hypertension AND patient compliance
      AND medication adherence. The main objective is to update the topic of
      therapeutic compliance in arterial hypertension worldwide, with special attention
      to Spain, as well as a critical evaluation of the evolution of therapeutic
      compliance over the period 1975-2011. After analysing 37 research studies
      published worldwide, the results were: total number of 8623 hypertensive
      patients, of whom 25.62% were non-compliers (n=2209; 95% CI; 23.82-27.42), and
      74.38% were compliers (n=6414; 95% CI; 73.32-75.44). The weighted average of non
      compliance was 37.60%. We conclude that the default rate in the pharmacological
      treatment of hypertension worldwide is high.

PMID- 23544777
TI  - [Organic and comorbid causes of depression: a first step].
AB  - The primary objective of this review is to obtain a clinical orientation as to
      evidence-supported common "other" causes of depressive symptomatology, which
      predominantly are: medical issues; life events; vitamin, mineral and diet-related
      deficiencies; and hormones. A secondary goal was to reflect those more frequent
      "other" causes in a checklist for clinical use, comprising also the preferred
      treatment (medical/dietary, antidepressants, or psychological) resulting from the
      available evidence. Medline, Cochrane and main related databases were searched
      from 4(th) October 2010 to 27(th) April 2011, no language limits, with keywords:
      depression; organic; comorbid; medication; life events; hormones; vitamin;
      mineral; diet; disease; as well as further searches into each upcoming possibly
      related issue. Total studies contemplated: 3.211; total studies reviewed: 301,
      with criteria of relevancy; date of study or review; size and type; journal
      status. Data were abstracted based upon probable clinical relevancy and use. The
      main results obtained were evidence-supported indications as to these other
      causes of depressive symptomatology, that warrant early screening, attention and
      treatment, possibly before antidepressant or psychological therapy is started.
      PRELIMINARY CONCLUSION: There appears to be a clinical rationale for early
      checking of a number of evidence-based causes of depressive symptoms for which
      first-line testing is readily available. In several cases clinical treatment may
      be simple, and improvements in depressive symptoms rapidly obtainable. Using a
      pre-treatment protocol, both patients and health systems could benefit from
      biological and comorbid causes of depressive symptoms being established early. An
      enhanced response to low-cost corrective measures can decrease the risk of
      suicide.

PMID- 23544778
TI  - [Vaccination against the human papilloma virus. Consensus statement 2011 of the
      scientific Spanish societies].

PMID- 23544779
TI  - [Presentation of a case of eosinophilia: practice management in primary care].
AB  - Eosinophilia is a common analytical disturbance in clinical practice and has a
      variety of aetiologies. Family physicians must be able to determine whether it is
      a benign finding or a serious disease. It is important to take a thorough
      clinical history and perform a physical examination for the correct differential
      diagnosis, as well as using the appropriate treatment guidelines specific to each
      cause. This is a case report of a man who presented with severe diarrhea and a
      laboratory finding of eosinophilia and his diagnosis and outcome.

PMID- 23544780
TI  - [Arnold-Chiari malformation and syringomyelia in primary care. A case report].
AB  - Rare diseases, due to their epidemiological characteristics, and sometimes to the
      non-specific symptoms, are difficult to diagnose routinely at Primary Care Level.
      A case is presented of Arnold Chiari malformation in a young male patient with
      early insidious presentation (neck pain and sub-occipital headaches) consulting
      due to the emergence of new symptoms (paresthesias, muscular weakness,
      cervicobrachial and radiating lumbar pain, and headaches after mild exertion).

PMID- 23544781
TI  - [Haemospermia: presentation of a case].
AB  - Haematospermia or haemospermia is a worrying symptom in the male population, but
      can be managed in many cases by primary care providers. As it is not often seen
      in clinics, it requires epidemiological knowledge and an appropriate clinical
      judgement to focus correctly on each case and to ensure the safety of our
      patients. The clinical history is the most important part of our intervention,
      and answering three questions, such as age, duration of bleeding and symptoms or
      risk factors may help in the diagnosis. More progress has been made in its
      diagnosis in recent years, due to determining the cause of the haematospermia in
      most cases.

PMID- 23544782
TI  - [Small fish, no thank you].

PMID- 23544783
TI  - [Staphylococcus lugdunensis and clear cell renal cell carcinoma].

PMID- 23544784
TI  - [Cat scratch disease. Is antibiotic treatment necessary?].

PMID- 23544786
TI  - Binding interactions in dimers of phenalenyl and closed-shell analogues.
AB  - Phenalenyl, an open-shell neutral radical that can form both pi-stacked dimers
      and conducting molecular crystals, has gained attention for its interesting and
      potentially useful electrical and magnetic properties. The properties of this
      complex physical system are fairly well understood, making it an ideal testing
      ground for the newly developed van der Waals density functional (vdW-DF). We
      invoke a simple approximation, allowing the vdW-DF to be used within spin
      polarized density functional theory and test this approximation on the pi-stacked
      phenalenyl dimer. The results indicate that the vdW-DF is capable of
      qualitatively describing the interaction between two neutral radicals in the pi
      stacked configuration, producing, in line with experiment, binding distances that
      are significantly below the sum of the van der Waals radii. This is a nontypical
      distance range where most other theories fail. We then investigate two
      hypothetical closed-shell analogues of this dimer, one formed by replacing the
      central carbon of phenalenyl with a nitrogen atom and the other formed by
      replacing the central carbon with a boron atom. In these cases, relatively strong
      interaction energies are obtained at more typical equilibrium distances for van
      der Waals dimers. The nitrogen-substituted dimer shows an unexpected rotational
      barrier that is dictated by the electronic kinetic energy within the system. The
      torsional curve of the boron-substituted dimer also exhibits a rotational
      barrier, but this is found to disappear when exact exchange is used in place of a
      local or semilocal exchange functional.

PMID- 23544787
TI  - Zinc catalyzed and mediated asymmetric propargylation of trifluoromethyl ketones
      with a propargyl boronate.
AB  - The development of zinc-mediated and -catalyzed asymmetric propargylations of
      trifluoromethyl ketones with a propargyl borolane and the N-isopropyl-l-proline
      ligand is presented. The methodology provided moderate to high stereoselectivity
      and was successfully applied on a multikilogram scale for the synthesis of the
      Glucocorticoid agonist BI 653048. A mechanism for the boron-zinc exchange with a
      propargyl borolane is proposed and supported by modeling at the density
      functional level of theory. A water acceleration effect on the zinc-catalyzed
      propargylation was discovered, which enabled a catalytic process to be achieved.
      Reaction progress analysis supports a predominately rate limiting exchange for
      the zinc-catalyzed propargylation. A catalytic amount of water is proposed to
      generate an intermediate that catalyzes the exchange, thereby facilitating the
      reaction with trifluoromethyl ketones.

PMID- 23544788
TI  - Articles from 2012. Editorial.

PMID- 23544789
TI  - Control region translocation and a tRNA gene inversion in the mitogenome of
      Paraplagusia japonica (Pleuronectiformes: Cynoglossidae).
AB  - Paraplagusia japonica (Cynoglossidae, Soleoidei) is characterized by a
      bilaterally asymmetrical and a series of fringes on the lips on the ocular side.
      Here we report for the first time the mitogenome of this tongue sole, which is
      16,694 bp in length, and the gene order has been reorganized. The tRNA-Gln gene
      translocated from the light strand (L-strand) to the heavy strand (H-strand),
      accompanied by tRNA-Ile gene shuffling. In addition, the putative control region
      translocated downstream to the place between the ND1 and the tRNA-Gln genes,
      leaving a 26-bp trace fragment in the original position. Nevertheless, the rest
      gene order is identical to that of the typical fish. In addition, it is the first
      report of the rare ATT as an initiation codon for ND3, and the ATP6 (- 26) and
      ND5 (+26) are unusually shorter or longer than those in other flatfish. These
      data will provide useful information for better understanding the molecular
      mechanisms of gene reorganization in fish mitogenome.

PMID- 23544790
TI  - Treatment algorithm for oral anticoagulant and antiplatelet therapy in epistaxis
      patients.
AB  - BACKGROUND AND OBJECTIVES: There is currently little published guidance on the
      management of anticoagulant and antiplatelet medication in patients admitted with
      epistaxis. The routine practice of withholding such medication in an attempt to
      control the epistaxis is common in the UK. However, this practice is not evidence
      based, is often unnecessary, and can be associated with significant morbidity.
      This study introduces a treatment algorithm for oral anticoagulant and
      antiplatelet therapy in epistaxis patients, validated through a completed audit
      cycle. METHODS: One hundred patients admitted with epistaxis to the University
      Hospital Southampton NHS Foundation Trust were studied via a two-audit cycle
      covering the implementation of a new treatment algorithm formulated jointly by
      the otolaryngology and haematology departments. RESULTS: On admission, 58 per
      cent of patients were taking some form of anticoagulant or antiplatelet
      medication. The number of patients having such medication withheld decreased
      significantly between the two audits, for all drugs studied (i.e. aspirin,
      clopidogrel and warfarin). There was no significant increase in re-bleeding or re
      admission rates between the audits. CONCLUSION: Implementation of this treatment
      algorithm would help standardise management for epistaxis patients taking
      anticoagulant or antiplatelet drugs, and should reduce morbidity associated with
      unnecessary routine discontinuation of such medication.

PMID- 23544791
TI  - In situ precipitation of Te nanoparticles in p-type BiSbTe and the effect on
      thermoelectric performance.
AB  - Through zone melting method, a certain amount of Te nano precipitations were in
      situ generated in the p-type BiSbTe matrix because of the addition of graphene.
      Both the microstructure and thermoelectric performance were investigated.
      Increased carrier concentration was obtained to improve the electrical
      performance, and the lattice thermal conductivity was simultaneously lowered
      about 25% by Te nano precipitations as phonon scattering centers. Consequently,
      an optimization of the thermoelectric figure-of-merit ZT between 375 and 550 K
      was achieved.

PMID- 23544792
TI  - Cystic ovaries in intermittently-suckled sows: follicle growth and endocrine
      profiles.
AB  - This paper presents follicle development and hormone profiles for sows with
      normal ovulation or cystic follicles during an intermittent-suckling (IS) regime
      that started at Day 14 of lactation. Sows were subjected to separation from their
      piglets during blocks of 6h or 12h. In total, 8 out of 52 sows developed cystic
      follicles; either full cystic ovaries (n=6) or partial ovulation (n=2). Increase
      in follicle size of these sows was similar to that of normal ovulating sows until
      pre-ovulatory size at Day 5 after the start of separation, but from then on
      became larger (P<0.05). LH surge was smaller or absent in sows that developed
      (partially) cystic ovaries (0.4 +/- 0.1 vs 3.6 +/- 0.3 ngmL(-1); P<0.01). Peak
      levels of oestradiol (E2) were similar but high E2 levels persisted in sows that
      developed (partly) cystic ovaries and duration of oestrus tended to be longer.
      The risk of developing (partly) cystic ovaries was higher when IS occurred in
      blocks of 6h versus 12h (33 vs 10%). In conclusion, the appearance of cystic
      ovaries at approximately Day 20 of ongoing lactation was related to an
      insufficient LH surge, as is also the case in non-lactating sows.

PMID- 23544793
TI  - The effect of spirometry on bronchial and alveolar nitric oxide in subjects with
      asthma.
AB  - OBJECTIVE: The effect of spirometric maneuvers on exhaled nitric oxide (NO) at
      the constant flow rate of 50 ml/s (FE(NO)) has been studied with equivocal
      results. Furthermore, the effects of spirometry on bronchial NO flux (J'aw(NO))
      and alveolar NO (CA(NO)), two measurements increasingly being used in clinical
      and research protocols, are unknown. The aim of this study was to evaluate the
      effect of spirometry on FE(NO), J'aw(NO), and CA(NO) in adults with asthma.
      METHODS: Forty-four adults with asthma were studied. To assess the impact of
      exhaled NO measurement itself on exhaled NO values, FE(NO), J'aw(NO), and CA(NO)
      were obtained twice, at baseline and after a resting period of 10 min. Then
      spirometry (with or without bronchodilator) was performed followed by exhaled NO
      measurements at 10 min. RESULTS: In the group with pre-bronchodilator study only
      (n = 26), mean (95% CI) values before spirometry were 37.3 ppb (22.2-52.4) for
      FE(NO), 2375 pl/s (1613-3137) for J'aw(NO), and 1.65 ppb (0.95-2.35) for CA(NO),
      compared with 35.5 ppb (21.1-49.0, p = .10), 2402 pl/s (1663-3141, p = .85), and
      1.60 ppb (0.64-2.56, p = .87) after spirometry, respectively. Spirometry-induced
      changes in exhaled NO values were also not significant in the group with both pre
      and post-bronchodilators (n = 18). Furthermore, changes in FE(NO), J'aw(NO), and
      CA(NO) values were similar in the two groups. CONCLUSIONS: Our findings
      demonstrate that spirometry (with or without bronchodilator) does not induce
      significant changes in bronchial NO flux or alveolar NO values. Therefore,
      exhaled NO values may be obtained after spirometric maneuvers.

PMID- 23544794
TI  - Nanoscale imaging of neutral atoms with a pulsed magnetic lens.
AB  - We present a scheme for imaging of neutral atoms to the nanoscale with a pulsed
      magnetic lens and show its viability through numerical calculations. This scheme
      achieves focal lengths on the order of several centimeters and focal spots of
      less than 10 nm. With these results, it is possible to create sub-10 nm
      structures on surfaces in a parallel and time-efficient manner. When used with
      metastable noble gas atoms, and in combination with electron spectroscopy, this
      scheme can create a chemically sensitive microscope which can probe surfaces on
      the nanometer scale.

PMID- 23544795
TI  - The interaction of fluoride with fluorogenic ureas: an ON1-OFF-ON2 response.
AB  - The anion binding tendencies of the two fluorogenic ureas L(1)H and L(2)H,
      containing the 2-anthracenyl and 1-pyrenyl moieties as signaling units,
      respectively, have been investigated in MeCN and DMSO by absorption, emission,
      and (1)H NMR spectroscopies. The formation of stable 1:1 receptor:anion H-bond
      complexes has been confirmed by structural studies on the crystalline
      [Bu4N][L(1)...Cl] and [Bu4N][L(2)H...CH3COO] salts. Complexation induces
      significant variations of the emission properties of L(1)H and L(2)H according to
      a multifaceted behavior, which depends upon the fluorogenic substituent, the
      solvent, and the basicity of the anion. Poorly basic anions (Cl(-), Br(-)) cause
      a red shift of the emission band(s). Carboxylates (CH3COO(-), C6H5COO(-)) induce
      fluorescence quenching due to the occurrence of an electron-transfer process
      taking place in the locally excited complex [*L-H...X](-). However, this excited
      complex may undergo an intracomplex proton transfer from one urea N-H fragment to
      the anion, to give the tautomeric excited complex [L...H-X](-)*, which emits at
      higher wavelength. F(-) displays a unique behavior: It forms with L(1)H a stable
      [L-H...F](-) complex which in the excited state undergoes intracomplex proton
      transfer, to give the poorly emissive excited tautomer [L...H-F](-)*. With L(2)H,
      on moderate addition of F(-), the 1:1 H-bond complex forms, and the blue
      fluorescence of pyrene is quenched. Large excess addition of F(-) promotes
      deprotonation of the ground-state complex, according to the equilibrium
      [L(2)H...F](-) + F(-) ? [L(2)](-) + HF2(-). The deprotonated receptor [L(2)](-)
      is distinctly emissive (yellow fluorescence), which generates the fluorimetric
      response ON(1)-OFF-ON(2) of receptor L(2)H with respect to F(-).

PMID- 23544796
TI  - The clinical and psychosocial impact of Peyronie's disease.
AB  - Peyronie's disease (PD) is characterized by the formation of palpable fibrotic
      tissue in the tunica albuginea of the penis. It is thought to manifest in
      response to recurrent microtrauma during erection in those with risk factors that
      may include wound-healing disorders. The initial stage of PD is thought to last
      from 6 to 18 months, and it is characterized by an inflammatory period with pain
      in approximately one-third of men. This initial phase is followed by a chronic
      phase when pain typically resolves and the deformity stabilizes with no
      additional plaque development. PD has been reported to develop in up to 9% of
      adult males according to published literature, but the incidence may be even
      higher. The most frequently affected age group is men between 50 and 59 years.
      Because of the associated penile deformity and effect on sexual relations,
      psychosocial distress is very common in those with PD. It has been reported to
      negatively affect self-image, sexual activity, intimacy, and mood, and it is
      often associated with depression and erectile dysfunction (ED). At this time,
      nonsurgical treatments are unreliable and have variable efficacy, and surgical
      treatments are reserved for those with disabling disfigurement. Moreover, surgery
      may result in loss of penile length and ED, and there are only a few physicians
      in the United States that perform such surgeries. There is a great need to
      increase awareness of PD in patients and general practitioners, to elucidate the
      pathogenesis of PD, and for the development of novel treatments for this
      disfiguring disease.

PMID- 23544797
TI  - A reactive molecular dynamics study of n-heptane pyrolysis at high temperature.
AB  - n-Heptane is the most important straight chain paraffin in the fossil-fuel
      industry. In this work, pyrolysis of n-heptane at high temperature is
      investigated by a series of ReaxFF based reactive molecular dynamic simulations.
      The pyrolysis correlated intermediate reactions, important product/intermediate
      distributions, and corresponding kinetics behaviors are systematically analyzed
      at atomistic level. The results indicate that the entire pyrolysis process is
      radical-dominated. The unimolecular dissociation is the main pathway of n-heptane
      decomposition. Initiation of the decomposition is mainly through C-C bond
      fission. Central C-C bonds would dissociate prior to the terminal ones. Besides,
      the Rice-Kossiakoff theory is proved for the pyrolysis of n-heptane at the
      atomistic level. To give a better description of the pyrolysis behavior, some
      alkane related intermolecular reactions should be considered in the mechanism.
      The apparent activation energy extracted from the present simulations is 43.02
      54.49 kcal/mol in the temperature range 2400-3000 K, which is reasonably
      consistent with the experimental results.

PMID- 23544798
TI  - Value of C-reactive protein in the assessment of organ-space surgical site
      infections after elective open and laparoscopic colorectal surgery.
AB  - BACKGROUND: Although C-reactive protein (CRP) has proved useful in the assessment
      of post-operative infections, its value at those time points useful to assess
      organ-space surgical site infection (OSI) after open and laparoscopic colorectal
      surgery has not been clarified. METHODS: We compared values of CRP on post
      operative days two and five and percentage of change between those days (Delta%D2
      5) in patients with and without OSI, after open (OPEN) and laparoscopic (LAP)
      colo-rectal surgery. Receiver-operating characteristic analysis was performed and
      indices of test performance of sensitivity, specificity, positive (PPV) and
      negative (NPV) predictive values, and likelihood ratios (LR+ and LR-) were
      assessed. RESULTS: The best CRP predictive values for OSI were D5 >120 mg/L (area
      under the curve [AUC] 0.959; 95% confidence interval [CI] 0.890-0.990) and
      Delta%D2-5 <40% (AUC 0.968; 95% CI 0.901-0.994; p=0.0001) in OPEN and D5 >66 mg/L
      (AUC 0.921; 95% CI 0.841-0.969) and Delta%D2-5 <48% (AUC 0.894-95% CI 0.806
      0.952; p=0.0001) in LAP. The best measure was NPV (100%; CI 93.6%-100% for D5 and
      Delta%D2-5 in OPEN and 98.4%, CI 91.3%-99.7% for D5 and 100%, CI 93.4%-100% for
      Delta%D2-5 in LAP). CONCLUSIONS: In patients with CRP <120.66 mg/L on post
      operative day 5 or a decay from post-operative day two to five of >40%-48% in
      OPEN and LAP, respectively, OSI may be ruled out and the patient discharged
      safely. Careful workup is needed in those patients with higher postoperative CRP
      concentrations or lower apparent decay values.

PMID- 23544799
TI  - Phlegmonous gastritis presenting as portal venous pneumatosis.
AB  - BACKGROUND: Phlegmonous gastritis is a rare and highly lethal primary bacterial
      infection of the stomach. The pathogenesis of this disease is understood poorly
      and no detailed description of its associated findings on computed tomography has
      been reported. METHODS: Case report and literature review. CASE REPORT: The
      authors describe an 84-year-old male with phlegmonous gastritis presenting as an
      abdominal catastrophe with portal venous pneumatosis observed on computed
      tomography. CONCLUSION: The association of portal venous air and related computed
      tomographic findings suggesting compromise of the gastric wall should be regarded
      with suspicion, and the possibility of phlegmonous gastritis should be
      entertained. Broad-spectrum antibiotic coverage should be instituted. Gram stain
      of the tissues of the stomach wall may help direct antibiotic therapy toward
      streptococcal infections as opposed to polymicrobial processes.

PMID- 23544800
TI  - Molybdenum nitride/N-doped carbon nanospheres for lithium-O2 battery cathode
      electrocatalyst.
AB  - Molybdenum nitride/N-doped carbon nanospheres (MoN/N-C) are synthesized by
      hydrothermal method followed by ammonia annealing. The as-prepared MoN/N-C
      nanospheres manifest considerable electrocatalytic activity toward oxygen
      reduction reaction in nonaqueous electrolytes because of its nanostructure and
      the synergetic effect between MoN and N-C. Furthermore, the MoN/N-C nanospheres
      are explored as cathode catalyst for Li-O2 batteries with tetra-(ethylene glycol)
      dimethyl ether as the electrolyte. The assembled batteries deliver alleviated
      overpotentials and improved battery lifespan, and their excellent performances
      should be attributed to the unique hierarchical structure and high fraction of
      surface active sites of cathode catalyst.

PMID- 23544802
TI  - Dehydrocoupling of dimethylamine borane catalyzed by Rh(PCy3)2H2Cl.
AB  - The Rh(III) species Rh(PCy3)2H2Cl is an effective catalyst (2 mol %, 298 K) for
      the dehydrogenation of H3B.NMe2H (0.072 M in 1,2-F2C6H4 solvent) to ultimately
      afford the dimeric aminoborane [H2BNMe2]2. Mechanistic studies on the early
      stages in the consumption of H3B.NMe2H, using initial rate and H/D exchange
      experiments, indicate possible dehydrogenation mechanisms that invoke turnover
      limiting N-H activation, which either precedes or follows B-H activation, to form
      H2B?NMe2, which then dimerizes to give [H2BNMe2]2. An additional detail is that
      the active catalyst Rh(PCy3)2H2Cl is in rapid equilibrium with an inactive
      dimeric species, [Rh(PCy3)H2Cl]2. The reaction of Rh(PCy3)2H2Cl with
      [Rh(PCy3)H2(H2)2][BAr(F)4] forms the halide-bridged adduct [Rh(PCy3)2H2(MU
      Cl)H2(PCy3)2Rh][BAr(F)4] (Ar(F) = 3,5-(CF3)2C6H3), which has been
      crystallographically characterized. This dinuclear cation dissociates on addition
      of H3B.NMe2H to re-form Rh(PCy3)2H2Cl and generate [Rh(PCy3)2H2(eta(2)
      H3B.NMe2H)][BAr(F)4]. The fate of the catalyst at low catalyst loadings (0.5 mol
      %) is also addressed, with the formation of an inactive borohydride species,
      Rh(PCy3)2H2(eta(2)-H2BH2), observed. On addition of H3B.NMe2H to Ir(PCy3)2H2Cl,
      the Ir congener Ir(PCy3)2H2(eta(2)-H2BH2) is formed, with concomitant generation
      of the salt [H2B(NMe2H)2]Cl.

PMID- 23544801
TI  - Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha
      conjugated gold nanoparticles for multimodal cancer therapy.
AB  - Surgery, radiation and chemotherapy remain the mainstay of current cancer
      therapy. However, treatment failure persists due to the inability to achieve
      complete local control of the tumor and curtail metastatic spread. Vascular
      disrupting agents (VDAs) are a class of promising systemic agents that are known
      to synergistically enhance radiation, chemotherapy or thermal treatments of solid
      tumors. Unfortunately, there is still an unmet need for VDAs with more favorable
      safety profiles and fewer side effects. Recent work has demonstrated that
      conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or
      nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor
      necrosis factor alpha, TNF-alpha). In this report, we show the potential of a
      gold conjugated TNF-alpha nanoparticle (NP-TNF) to improve multimodal cancer
      therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of
      prostate cancer, we found that NP-TNF disrupts endothelial barrier function and
      induces a significant increase in vascular permeability within the first 1-2 h
      followed by a dramatic 80% drop in perfusion 2-6 h after systemic administration.
      We also demonstrate that the tumor response to the nanoparticle can be verified
      using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in
      clinical use. Additionally, multimodal treatment with thermal therapies at the
      perfusion nadir in the sub- and supraphysiological temperature regimes increases
      tumor volumetric destruction by over 60% and leads to significant tumor growth
      delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance
      thermal therapy in the absence of neutrophil recruitment, suggesting that
      immune/inflammatory regulation is not central to its power as part of a
      multimodal approach. Our data demonstrate the potential of nanoparticle
      conjugated VDAs to significantly improve cancer therapy by preconditioning tumor
      vasculature to a secondary insult in a targeted manner. We anticipate our work to
      direct investigations into more potent tumor vasculature specific combinations of
      VDAs and nanoparticles with the goal of transitioning optimal regimens into
      clinical trials.

PMID- 23544803
TI  - Antipyretic use in children: more than just temperature.

PMID- 23544804
TI  - Oral Ibuprofen and the patent ductus arteriosus: a new approach to an old
      problem.

PMID- 23544805
TI  - Recommendations for long-term home oxygen therapy in children and adolescents.
AB  - OBJECTIVE: To advise pediatricians, neonatologists, pulmonologists, pediatric
      pulmonologists, and other professionals in the area on the main indications and
      characteristics of long-term home oxygen therapy in children and adolescents.
      DATA SOURCE: A literature search was carried out in the MEDLINE/PubMed database
      (1990 to 2011). Additionally, references from selected studies were included. As
      consistent scientific evidence does not exist for many aspects, some of the
      recommendations were based on clinical experience. DATA SYNTHESIS: Long-term home
      oxygen therapy has been a growing practice in pediatric patients and is indicated
      in bronchopulmonary dysplasia, cystic fibrosis, bronchiolitis obliterans,
      interstitial lung diseases, and pulmonary hypertension, among others. The
      benefits are: decrease in hospitalizations, optimization of physical growth and
      neurological development, improvement of exercise tolerance and quality of sleep,
      and prevention of pulmonary hypertension/cor pulmonale. The levels of oxygen
      saturation indicative for oxygen therapy differ from those established for adults
      with chronic obstructive pulmonary disease, and vary according to age and
      disease. Pulse oximetry is used to evaluate oxygen saturation; arterial blood gas
      is unnecessary. There are three available sources of oxygen: gas cylinders,
      liquid oxygen, and oxygen concentrators. The flows used are usually smaller, as
      are the number of hours/day needed when compared to the use in adults. Some
      diseases show improvement and oxygen therapy discontinuation is possible.
      CONCLUSIONS: Long-term home oxygen therapy is increasingly common in pediatrics
      and has many indications. There are relevant particularities when compared to its
      use in adults, regarding indications, directions for use, and monitoring.

PMID- 23544806
TI  - Effectiveness of probiotics in the prophylaxis of necrotizing enterocolitis in
      preterm neonates: a systematic review and meta-analysis.
AB  - OBJECTIVE: To elucidate the benefits of using probiotics in the prevention of
      necrotizing enterocolitis (NEC) and its complications in preterm newborns.
      METHOD: This was a systematic review of randomized controlled trials, which
      included studies retrieved from three databases (MEDLINE, Embase, and LILACS),
      using a combination of the terms (necrotizing enterocolitis) AND (probiotics).
      RESULTS: 11 randomized trials were included, totaling 2,887 patients, 1,431 in
      the probiotic group and 1,456 in the control group. There was a reduction in the
      incidence of NEC (NNT=25), overall death (NNT=34), and neonatal sepsis (NNT=34)
      in the probiotic group compared to the control group. Patients that received
      probiotic supplementation had lower food reintroduction time (p<0.001) and
      hospitalization time (p<0.001) when compared to those not receiving probiotics.
      There was no difference in mortality caused by NEC. CONCLUSION: In premature
      newborns, the use of probiotics is effective as a prophylaxis for NEC and its
      complications.

PMID- 23544807
TI  - Therapeutic procedures and use of alternating antipyretic drugs for fever
      management in children.
AB  - OBJECTIVE: The evidence on the effectiveness of alternating antipyretics in fever
      management is scarce and indicates clinically negligible differences. The present
      study aimed to describe therapeutic procedures and the use of alternating
      antipyretics in children, and to evaluate associated factors. METHODS: This was a
      cross-sectional study with 692 children aged 0 to 6 years, living in Southern
      Brazil. Household interviews of the children's caregivers were conducted through
      cluster sampling using a structured questionnaire. A descriptive analysis was
      carried out, and the association between the use of alternating antipyretics and
      sociodemographic factors was evaluated. A total of 630 cases were analyzed
      (91.0%), corresponding to children with a history of fever. RESULTS:
      Approximately 73% of caregivers reported that the first measure adopted during
      the last fever episode was the administration of medication. The mean temperature
      considered as fever by caregivers was 37.4 degrees C, and as high fever, 38.7
      degrees C. The use of alternating antipyretic therapy was reported by 26.7% of
      respondents, justified by the lack of response to monotherapy and medical
      indication, in most cases. The drugs most often used were dipyrone and
      paracetamol. Children whose primary caregiver was a parent with higher
      socioeconomic status and higher educational level received more alternating
      medications. Approximately 70% of the doses used were below the minimum
      recommended dose for the treatment of fever. CONCLUSIONS: The use of medication
      to control fever is a common practice, including alternating antipyretic
      regimens. Most caregivers consider as fever temperatures lower than those
      established and they reported lack of response to monotherapy and medical
      indication as the main reasons for alternating medication.

PMID- 23544808
TI  - Comparison of oral Ibuprofen and intravenous indomethacin for the treatment of
      patent ductus arteriosus in extremely low birth weight infants.
AB  - OBJECTIVE: There are few published reports concerning the efficacy of oral
      ibuprofen for the treatment of patent ductus arteriosus (PDA) in extremely low
      birth weight (ELBW) infants. Oral ibuprofen was compared to intravenous
      indomethacin regarding efficacy and safety in the treatment of PDA in infants
      weighting less than 1,000g at birth. METHOD: This was a retrospective study in a
      single center. Data on ELBW infants who had an echocardiographically confirmed
      PDA were collected. The infants were treated with either intravenous indomethacin
      or oral ibuprofen. Rate of ductal closure, need for additional treatment, drug
      related side effects or complications, and mortality were compared between the
      two treatment groups. RESULT: 26 infants who received indomethacin and 22 infants
      who received ibuprofen were studied. The overall rate of ductal closure was
      similar between the two treatments: it occurred in 23 of 26 infants (88.5%)
      treated with indomethacin, and in 18 of 22 infants (81.8%) treated with ibuprofen
      (p=0.40). The rate of surgical ligation (11.5% versus 18.2%; p=0.40) did not
      differ significantly between the two treatment groups. No significant difference
      was found in post-treatment serum creatinine concentrations between the two
      groups. There were no significant differences regarding additional side effects
      or complications. CONCLUSION: In ELBW infants, oral ibuprofen is as efficacious
      as intravenous indomethacin for the treatment of PDA. There were no differences
      between the two drugs with respect to safety. Oral ibuprofen could be used as an
      alternative agent for the treatment of PDA in ELBW infants.

PMID- 23544809
TI  - The impact of cystic fibrosis on the immunologic profile of pediatric patients.
AB  - OBJECTIVE: To compare the immunologic state of 44 pediatric patients with cystic
      fibrosis (CF) with a control group consisting of 16 healthy individuals. METHODS:
      CF patients aged 3 to 12 years with moderate to good clinical score were selected
      for the study. Erythrocytic glutathione, production of reactive oxygen species,
      cytokines (TNF-a, IFN-g, IL-8, IL-6, IL-10) in peripheral blood mononuclear cells
      cultures under spontaneous and BCG- or PHA-stimulated conditions, serum
      concentrations of TGF-b2, IgA, IgG, IgM, IgE, and salivary IgA were evaluated.
      RESULTS: The spontaneous production of TNF-a, IL-6, and IL-10, the PHA-stimulated
      production of IL-6, and the serum TGF-b2, IgA, and IgG were increased in samples
      from CF patients. Healthy subjects had a higher production of TNF-a in response
      to BCG. CONCLUSION: Although CF patients appeared clinically stable, the results
      of their peripheral blood examinations demonstrated an impact on the immune
      system.

PMID- 23544810
TI  - High-frequency oscillatory ventilation in children: a 10-year experience.
AB  - OBJECTIVES: The aim of the study was to describe the experience with high
      frequency oscillatory ventilation (HFOV) in a Portuguese Pediatric Critical Care
      Unit, and to evaluate whether HFOV allowed improvement in oxygenation and
      ventilation. METHODS: This was a retrospective observational cohort study of
      children ventilated by HFOV between January, 2002 and December, 2011. The
      following parameters were recorded: demographic and clinical data, and blood
      gases and ventilatory parameters during the first 48 hours of HFOV. RESULTS: 80
      children were included, with a median age of 1.5 months (min: one week; max: 36
      months). Pneumonia (n=50; 62.5%) and bronchiolitis (n=18; 22.5%) were the main
      diagnoses. Approximately 40% (n=32) of the patients developed acute respiratory
      distress syndrome (ARDS). Conventional mechanical ventilation was used in 68
      (85%) of patients prior to HFOV. All patients who started HFOV had hypoxemia, and
      56 (70%) also presented persistent hypercapnia. Two hours after starting HFOV, a
      significant improvement in SatO2/FiO2 ratio (128+/-0.63 vs. 163+/-0.72; p<0.001)
      that was sustained up to 24 hours of HFOV and a decrease in FiO2 were observed.
      Since the beginning of HFOV, the mean PCO2 significantly decreased (87+/-33 vs.
      66+/-25; p<0.001), and the pH significantly improved (7.21+/-0.17 vs. 7.32+/
      0.15; p<0.001). Overall survival was 83.8%. CONCLUSIONS: HFOV enabled an
      improvement in hypercapnia and oxygenation. It is a safe option for the treatment
      of ARDS and severe small airway diseases.

PMID- 23544811
TI  - Hypertriglyceridemic waist phenotype: association with metabolic abnormalities in
      adolescents.
AB  - OBJECTIVE: This study aimed to identify the prevalence of hypertriglyceridemic
      waist (HTW) phenotype, and to evaluate its association with metabolic
      abnormalities in adolescents of low socioeconomic status. METHOD: This was a
      cross-sectional study with a random sample of 1,076 adolescents between 11 and 17
      years, of both genders, from public schools. The participants underwent
      anthropometric measurements (weight, height, and waist circumference), and levels
      of total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), non-HDL cholesterol, triglyceride (TG), and
      fasting glucose were measured. Information regarding the socioeconomic status of
      the participants' families was obtained. The HTW phenotype was defined by the
      simultaneous presence of increased waist circumference (>= 90(th) percentile for
      age and gender) and serum triglyceride levels (>= 100mg/dL). A logistic
      regression analysis was used to evaluate the associations of interest. RESULTS:
      The prevalence of HTW phenotype was 7.2% among the adolescents, being higher in
      the presence of obesity (63.4%) and high levels of non-HDL cholesterol (16.6%)
      and LDL-C (13.7%). The bivariate analysis indicated that, of the metabolic
      variables, only blood glucose was not associated with the HTW phenotype.
      Multivariate analysis adjusted for age and gender indicated that the HTW
      phenotype was positively associated with high non-HDL cholesterol (odds ratio:
      7.0; 95% CI: 3.9-12.6) and low HDL-C levels (odds ratio: 2.7; 95% CI: 1.5-4.8).
      CONCLUSIONS: This study demonstrated that the HTW phenotype was associated with
      an atherogenic lipid profile, and this phenotype is suggested as a screening tool
      to identify adolescents with metabolic alterations.

PMID- 23544812
TI  - Acute lymphoblastic leukemia in infants: 20 years of experience.
AB  - OBJECTIVE: To analyze patients younger than 2 years with acute lymphoblastic
      leukemia, treated in the period between 1990 and 2010 in a state reference
      center. METHODS: This was a clinical-epidemiological, cross-sectional,
      observational, and descriptive study. It included patients younger than 2 years
      with acute lymphoblastic leukemia, treated in the period of 1990 to 2010 in a
      pediatric oncology unit of a state reference center, totaling 41 cases. RESULTS:
      All patients were white ethnicity, and 60.9% were females. Regarding age, 24.38%
      were younger than 6 months, 17.07% were between 6 months and 1 year, and 58.53%
      were older than 1 year. The age of 6 months was statistically significant for the
      outcome of death. Predominant signs and symptoms were fever, bruising, and
      petechiae. A leukocyte count > 100,000 was found in 34.14% of cases, hemoglobin
      count < 11 in 95.13%, and platelet count < 100,000 in 75.61. Infiltration of
      central nervous system was present in 12.91% of patients. According to the
      lineage, B-cell lineage predominated (73%), but the T-cell line was statistically
      significant for death. 39% of patients had disease recurrence. In relation to
      vital status, 70.73% of the patients died; septic shock was the main cause.
      CONCLUSIONS: Acute lymphoblastic leukemia in infants has a high mortality rate,
      especially in children under 1 year and those with T-cell derived lineage.

PMID- 23544813
TI  - Screening for motor dysgraphia in public schools.
AB  - OBJECTIVE: To screen for warning signs of dysgraphia in schoolchildren at the
      sixth grade of elementary school. METHOD: This was a descriptive, exploratory,
      cross-sectional cohort study performed with 630 schoolchildren assessed through
      the (adapted) Analytical Dysgraphia Inventory, which recognizes difficulties in
      writing through the tracing the graphics. RESULTS: A total of 22% (n=138) of the
      sample presented all indications of dysgraphia; the most prevalent indicator was
      ascending/descending/fluctuating lines (53.6%). When the indicators were
      correlated to gender, males showed a significant difference (p<0.05) in most of
      them. Among the warning signs of co-occurrences, dyslexia was the most prevalent
      indicator (22%). CONCLUSION: Given the large number of warning signs of
      dysgraphia observed in schoolchildren, it is advisable to screen for these signs,
      in order to implement early interventions.

PMID- 23544814
TI  - Characteristics and factors associated with health care in children younger than
      1 year with very low birth weight.
AB  - OBJECTIVES: To identify the characteristics of health care in infants with very
      low birth weight during the first year of life and the factors associated with
      this care. METHODS: This was a descriptive study with an analytical component
      conducted in the city of Maceio, Northeastern Brazil, with a sample of 53
      children with a median age of five months at the time of the interview, and their
      mothers. The mothers were interviewed at home regarding socioeconomic and
      demographic data and health care provided for the child. Health care was assessed
      through an index using 16 variables related to the recommended actions for this
      type of care. RESULTS: Multivariate linear regression analysis showed that
      maternal education and family income were the variables that best explained the
      health care index variation (18.9%), followed by parity (6.6%), and breastfeeding
      at the time of the interview (6.9%). CONCLUSIONS: Considering that families with
      lower socioeconomic status, women with a higher number of children, and women who
      did not breastfeed were factors associated with poor health care of children born
      with very low birth weight, these variables should be included in measures of
      public health planning.

PMID- 23544815
TI  - Factors associated with physical aggression in pregnant women and adverse
      outcomes for the newborn.
AB  - OBJECTIVE: To assess the socioeconomic, demographic, and reproductive factors
      associated with physical aggression during pregnancy, and the negative outcomes
      for the newborn in two groups of women: adolescents and young adults. METHOD:
      Cross-sectional study with a sample of 8,961 mothers who were admitted to
      hospitals of the city of Rio de Janeiro during delivery. To test the hypothesis
      of homogeneity of proportions, the chi-squared test was used. Odds ratio and
      confidence intervals were estimated using logistic regression. RESULTS: 5.0% of
      the adolescents and 2.5% of the young adult women suffered physical violence
      during pregnancy. In both groups, the variables associated with physical abuse
      were lower educational level, lower support from the child's father, and more
      attempts to interrupt the pregnancy. The increase in alcohol consumption was
      associated with physical abuse only in the group of adolescents; illicit drug use
      was only associated with physical abuse in young adults. The children of abused
      mothers had a two-fold increased chance of neonatal death, and a three-fold
      increased chance of post-neonatal death. Conversely, good quality prenatal care
      reduced the chance of physical aggression during pregnancy. CONCLUSIONS: The
      results emphasize the increased chance of neonatal and post-neonatal mortality
      among children of victims of physical abuse during pregnancy, and indicate the
      importance of prenatal care to identify women at higher risk of suffering
      aggression, the appropriate time to provide measures of protection and care for
      mother and baby.

PMID- 23544816
TI  - Bone mass in children and adolescents infected with human immunodeficiency virus.
AB  - OBJECTIVE: To describe bone mineral density (BMD) and bone mineral content (BMC)
      in children and adolescents infected with the human immunodeficiency virus (HIV),
      and to compare them with data from the National Health and Nutrition Examination
      Survey IV (NHANES IV). METHOD: The study included 48 children and adolescents (7
      to 17 years old) infected with HIV through vertical transmission. BMC and BMD
      were measured by dual energy absorptiometry X-ray, by calculating z-scores based
      on data from NHANES IV. The information on clinical and laboratory parameters of
      infection by HIV was obtained from medical records. Physical activity, calcium
      intake, and skeletal maturation were also assessed. Descriptive and inferential
      statistical procedures were used, with levels of significance set at 5%. RESULTS:
      Seropositive patients presented lower values compared to data from NHANES IV in
      all z-scores of bone mass (mean=-0.52 to -1.22, SD=0.91 and 0.84, respectively).
      Based on the subtotal z-BMD, there was a prevalence of 16.7% of children and
      adolescents with low bone mass for age. Individuals using protease inhibitors
      presented a lower total z-BMD when compared to the group that did not use (-1.31
      vs. -0.79, p=0.02). There were no bone mass differences in relation to physical
      activity and calcium intake. CONCLUSIONS: In the present sample children and
      adolescents living with HIV have low bone mass for age, and the use of protease
      inhibitors appears to be related to such decreases.

PMID- 23544817
TI  - Alcohol consumption and violence among Argentine adolescents.
AB  - OBJECTIVE: This study investigated the association between alcohol and violence
      among Argentine youth. METHODS: Data from the 2007 Argentina Global School-based
      Student Health Survey (GSHS), a nationally representative survey of middle school
      students, were examined using age-adjusted logistic regression models. RESULTS:
      Of the 1,328 participating students aged 13 to 15 years old, 51.9% reported
      drinking alcohol in the previous month, with higher rates among males (p=0.04)
      and older students (p<0.01). Both male and female drinkers were nearly twice as
      likely as non-drinkers to report being physically attacked, being in a physical
      fight, and having thoughts about self-directed violence. Among drinkers, those
      who reported poor mental health, were victims of bullying, used tobacco or drugs,
      or skipped school without permission were approximately twice as likely as other
      drinkers to have engaged in violent activities. CONCLUSION: Public health
      interventions targeting violence among young adolescents should be developed in
      combination with alcohol education programs.

PMID- 23544818
TI  - Chronic rhinosinusitis assessment using the Adelaide Disease Severity Score.
AB  - AIM: This study aimed to validate the use of the Adelaide Disease Severity Score
      for the assessment of chronic rhinosinusitis. STUDY DESIGN: A prospective cohort
      study supplying level 2b evidence. METHODS: Forty-eight patients, scheduled for
      endoscopic sinus surgery for failed management of chronic rhinosinusitis,
      completed the Sino-Nasal Outcome Test 22 and the Adelaide Disease Severity Score
      tool (the latter assessing symptoms (i.e. nasal obstruction, rhinorrhoea, post
      nasal drip, headache or facial pain, and olfaction) and quality of life). Lund
      Mackay computed tomography scores and Lund-Kennedy endoscopic scores were also
      recorded. The Adelaide Disease Severity Score results were then compared with
      those of the other three tools to assess correlation. RESULTS: Mean scores (95
      per cent confidence intervals) were 22.31 (21.47-24.15) for the Adelaide Disease
      Severity Score and 30.6 (27.15-34.05) for the Sino-Nasal Outcome Test 22; there
      was a statistically significant correlation (Spearman coefficient = 0.45; p =
      0.0015). A statistically significant correlation was also noted with the Lund
      Mackay score (p = 0.04) and with the Lund-Kennedy score (p = 0.03). CONCLUSION:
      The Adelaide Disease Severity Score is a simple, valid tool for clinical
      assessment of chronic rhinosinusitis, which correlates well with the Sino-Nasal
      Outcome Test 22, Lund-Mackay and Lund-Kennedy tools.

PMID- 23544819
TI  - Osteoporosis diagnosis and medical treatment.
AB  - Osteoporosis, the presence of either low bone mineral density or a history of a
      fragility fracture, is known to be associated with an increased risk of future
      fracture. Fracture prevention is possible through use of both nonpharmacologic
      and prescription treatments. Despite recent controversy regarding the safety of
      calcium supplementation and the appropriate dosing of calcium and vitamin D,
      calcium and vitamin D remain an important part of bone health. However,
      prescription osteoporosis treatments should be considered for those at higher
      risk for fracture, and there are currently several treatment options available.

PMID- 23544820
TI  - Bisphosphonate therapy and atypical fractures.
AB  - Atypical femoral fractures have attracted a great deal of attention and
      controversy in the osteoporosis community because of their association with
      prolonged bisphosphonate therapy. The purpose of this article is to review the
      epidemiologic evidence linking bisphosphonates to atypical fractures and to
      highlight the potential pathologic mechanisms involved in such fractures. A
      management plan is provided based on the available evidence.

PMID- 23544821
TI  - Cognitive dysfunction in hip fracture patients.
AB  - Hip fractures represent a widespread morbidity among the geriatric population. In
      North America, more than 320,000 hip fractures are sustained annually, a number
      that is expected to increase dramatically as the population continues to age.
      Disorders of cognition, primarily dementia and delirium, also have a higher-than
      average incidence and prevalence among the geriatric population. The co
      occurrence of cognitive dysfunction and hip fracture is an important entity for
      orthopedic surgeons and other clinicians involved in hip fracture care to
      recognize. This article provides an overview of the currently available evidence
      regarding cognitive dysfunction, specifically dementia and delirium, in patients
      with hip fractures.

PMID- 23544822
TI  - Hip fracture protocols: what have we changed?
AB  - Early surgical intervention is thought to reduce in-hospital morbidity and
      mortality as well as short-term mortality rates for elderly patients with hip
      fractures. However, hip fractures are also thought to be a symptom of progressive
      decline in elderly patients with multiple medical comorbidities. A measured
      approach to medical optimization, which may preclude rapid surgical intervention,
      is often required to improve the patient's ability to resume a prefracture
      standard of living. Of late, new models of geriatric hip-fracture care have
      emerged, most of which entail early involvement of geriatricians and
      interdisciplinary care pathways, while continuing to focus on rapid surgical
      treatment.

PMID- 23544823
TI  - Biomechanical considerations for surgical stabilization of osteoporotic
      fractures.
AB  - The incidence of osteoporotic fractures has been steadily rising along with the
      aging of the population. Surgical management of these fractures can be a
      challenge to orthopedic surgeons. Diminished bone mass and frequent comminution
      make fixation difficult. Advancements in implant design and fixation techniques
      have served to address these challenges and when properly applied, can improve
      overall outcome. The purpose of this review is to describe fixation challenges of
      common osteoporotic fractures and provide options for successful treatment.

PMID- 23544824
TI  - The osteoporotic acetabular fracture.
AB  - Fractures of the acetabulum are some of the most challenging fractures that face
      orthopedic surgeons. In geriatric patients, these challenges are enhanced by the
      complexity of fracture patterns, the poor biomechanical characteristics of
      osteoporotic bone, and the comorbidities present in this population. Nonsurgical
      management is preferable when the fracture is stable enough to allow
      mobilization, and healing in a functional position can be expected. When
      significant displacement and/or hip instability are present, operative management
      is preferred in most patients, which may include open reduction and internal
      fixation with or without total hip arthroplasty.

PMID- 23544825
TI  - Osteoporotic pelvic ring injuries.
AB  - As with most fractures associated with osteoporosis, the incidence of pelvic ring
      injuries in this population of patients is rising rapidly. Osteoporotic pelvic
      ring injuries are exceedingly different in their etiology, natural history, and
      treatment from the more recognizable patterns in young patients with high-energy
      pelvic ring injuries. Recognition of a potentially unstable fracture pattern,
      careful evaluation of the ambulatory and functional status of each patient before
      injury, and the potential pitfalls and benefits of operative versus nonoperative
      care are critical to the effective treatment.

PMID- 23544826
TI  - Osteoporotic ankle fractures.
AB  - Ankle fractures are one of the most common injuries in the elderly and their
      incidence is anticipated to increase over the next 20 years. Appropriate
      management of ankle fractures in this population requires an understanding of the
      issues unique to the elderly. Osteoporosis must be considered when counseling
      patients about their ankle fracture. Good outcomes can be achieved with surgical
      fixation of ankle fractures in the elderly. Postoperative complications are
      higher in patients with diabetes and peripheral vascular disease, and in patients
      who smoke. This article reviews how to evaluate and treat ankle fractures in
      elderly patients with osteoporosis, evaluates the outcomes, and discusses
      surgical techniques.

PMID- 23544827
TI  - Surgical stabilization of the spine in the osteoporotic patient.
AB  - Osteoporosis affects millions of US citizens, and millions more are at risk for
      developing the disease. Several operative techniques are available to the spine
      surgeon to provide care for those affected by osteoporosis. The types of
      osteoporosis, common surgical complications, medical optimization, and surgical
      techniques in the osteoporotic spine are reviewed, with an emphasis on
      preoperative planning.

PMID- 23544828
TI  - Managing atrophic nonunion in the geriatric population: incidence, distribution,
      and causes.
AB  - Osteoporosis is a systemic disease that affects millions of people worldwide. It
      is estimated that 50% of women and approximately 20% of men more than 50 years of
      age will sustain a fragility fracture. The cause of nonunion in patients with
      osteoporosis is likely multifactorial, and includes age-related changes in
      fracture repair as well as challenges in achieving stable internal fixation. This
      article discusses fracture healing in patients with osteoporosis and the
      principles of fixation. Pharmacotherapy for the patient with osteoporosis is also
      discussed.

PMID- 23544829
TI  - Osteoporosis and fragility fractures.

PMID- 23544830
TI  - Role of the unstructured N-terminal domain of the hAPE1 (human
      apurinic/apyrimidinic endonuclease 1) in the modulation of its interaction with
      nucleic acids and NPM1 (nucleophosmin).
AB  - The hAPE1 (human apurinic/apyrimidinic endonuclease 1) is an essential enzyme,
      being the main abasic endonuclease in higher eukaryotes. However, there is strong
      evidence to show that hAPE1 can directly bind specific gene promoters, thus
      modulating their transcriptional activity, even in the absence of specific DNA
      damage. Recent findings, moreover, suggest a role for hAPE1 in RNA processing,
      which is modulated by the interaction with NPM1 (nucleophosmin). Independent
      domains account for many activities of hAPE1; however, whereas the endonuclease
      and the redox-active portions of the protein are well characterized, a better
      understanding of the role of the unstructured N-terminal region is needed. In the
      present study, we characterized the requirements for the interaction of hAPE1
      with NPM1 and undamaged nucleic acids. We show that DNA/RNA secondary structure
      has an impact on hAPE1 binding in the absence of damage. Biochemical studies,
      using the isolated N-terminal region of the protein, reveal that the hAPE1 N
      terminal domain represents an evolutionary gain of function, since its
      composition affects the protein's stability and ability to interact with both
      nucleic acids and NPM1. Although required, however, this region is not sufficient
      itself to stably interact with DNA or NPM1.

PMID- 23544831
TI  - Associations of Helicobacter pylori infection and cytotoxin-associated gene A
      status with autoimmune thyroid diseases: a meta-analysis.
AB  - BACKGROUND: Helicobacter pylori infection is reportedly associated with
      extradigestive diseases such as immune thrombocytopenic purpura and coronary
      heart disease. The risk factors for autoimmune thyroid diseases (ATDs) remain
      largely unknown, and whether H. pylori infection is associated with ATDs is still
      controversial. The aim of this meta-analysis was to determine the association
      between H. pylori infection and ATDs. METHODS: Studies comparing the prevalence
      rate of H. pylori infection in patients with ATDs and healthy controls, published
      in English, were identified through a systematic search in MEDLINE and EMBAS up
      to June 2012. Serological or nonserological tests were used to confirm H. pylori
      infection and the presence of cytotoxin-associated gene A (CagA) antigens. The
      odds ratios (OR) and associated 95% confidence intervals [CI] were obtained.
      RESULTS: Seven studies involving a total of 862 patients met the inclusion
      criteria and thus were included in our meta-analysis. Overall, H. pylori
      infection was associated with ATDs (OR 1.92 [CI 1.41-2.61]); the association was
      significant for Graves' disease (OR 4.35 [CI 2.48-7.64]) but not for Hashimoto's
      thyroiditis (OR 1.45 [CI 0.92-2.26], p=0.11). No association was observed in the
      subanalysis of studies using only enzyme-linked immunosorbent assay to detect H.
      pylori infection (OR 1.38 [CI 0.86-2.19], p=0.18). Five of the seven articles
      reported the association of CagA seroprevalence and ATDs. CagA seropositivity
      significantly increased the risk for ATDs by 2.24-fold [CI 1.06-4.75].
      CONCLUSIONS: Both the prevalence of H. pylori infection and the seroprevalence of
      CagA-positive strains are associated with ATDs. These findings suggest that H.
      pylori infection potentially plays a part in the development of ATDs.

PMID- 23544832
TI  - The complete mitochondrial genome of Chinese sucker Myxocyprinus asiaticus
      (Cypriniformes, Catostomidae).
AB  - In this study, the complete mitogenome sequence of Chinese sucker Myxocyprinus
      asiaticus (Cypriniformes, Catostomidae) has been amplified and sequenced by
      employing long polymerase chain reaction method. The mitogenome, consisting of
      16,636 base pairs (bp), had the typical vertebrate mitochondrial gene
      arrangement, including 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal
      RNAs genes, and a noncoding control region (CR). CR of 944 bp length is located
      between tRNA(Pro) and tRNA(Phe). The overall base composition of M. asiaticus is
      28.62% for A, 27.90% for C, 24.8% for T, and 18.70% for G, with a slight AT bias
      of 53.40%. The complete mitogenome may provide important DNA molecular data for
      further phylogenetic analyses for higher taxa of teleost fishes especially for
      the members of Cypriniformes.

PMID- 23544838
TI  - Segmented assimilation and attitudes toward psychotherapy: a moderated mediation
      analysis.
AB  - The present study examines the relations between acculturative stress, mental
      health, and attitudes toward psychotherapy, and whether these relations are the
      same for immigrants of color and White immigrants. This study predicted that
      acculturative stress would have a significant, negative relation with attitudes
      toward psychotherapy and that this relation would be moderated by race
      (immigrants of color and White immigrants) so that as acculturative stress
      increases, attitudes toward psychotherapy become more negative for immigrants of
      color but not White immigrants. Finally, mental health was predicted to mediate
      the relation between acculturative stress and attitudes toward psychotherapy for
      immigrants of color, but not White immigrants. Participants were 149 first
      generation, immigrant, young adults, between the ages of 18 and 29, who
      identified as White, Black, Latino, or Asian. A significant negative correlation
      was found between acculturative stress and attitudes toward psychotherapy. A
      moderated mediation analysis demonstrated that the negative relation between
      acculturative stress and attitudes toward psychotherapy was mediated by mental
      health symptoms for immigrants of color but not White immigrants.

PMID- 23544839
TI  - Family support, self-esteem, and perceived racial discrimination among Asian
      American male college students.
AB  - This study was conducted to examine under what situation (i.e., when individuals
      used more or less family support) and for whom (i.e., those with high or low self
      esteem) perceived racial discrimination would or would not have a significant
      positive association with psychological distress. A total of 95 Asian American
      male college students completed an online survey. A hierarchical regression
      analysis indicated a significant 3-way interaction of family support, self
      esteem, and perceived racial discrimination in predicting psychological distress
      after controlling for perceived general stress. A simple effect analysis was used
      to explore the nature of the interaction. When Asian American male college
      students used more family support to cope with racial discrimination, the
      association between perceived racial discrimination and psychological distress
      was not significant for those with high or low self-esteem. The result from the
      simple interaction indicated that, when more family support was used, the 2
      slopes for high and low self-esteem were not significantly different from each
      other. Conversely, when they used less family support, the association between
      perceived racial discrimination and psychological distress was not significant
      for those with high self-esteem, but was significantly positive for those with
      low self-esteem. The result from the simple interaction indicated that, when less
      family support was used, the slopes for high and low self-esteem were
      significantly different. The result suggested that low use of family support may
      put these male students with low self-esteem at risk for psychological distress.
      Limitations, future research directions, and clinical implications were
      discussed.

PMID- 23544840
TI  - Next generation of mammalian target of rapamycin inhibitors for the treatment of
      cancer.
AB  - INTRODUCTION: Because of the central role of the mammalian target of rapamycin
      (mTOR) pathway in the control and distribution of signals essential for mRNA
      translation of mitogenic genes and generation of oncogenic proteins, effective
      targeting of mTOR remains a major goal in medical oncology. AREAS COVERED: This
      article summarizes preclinical and clinical studies relating to the next
      generation of mTOR inhibitors. While rapalogs have shown activity in the
      treatment of breast, renal and neuroendocrine tumors, these agents do not block
      mTORC2, one of the two major protein complexes in which mTOR participates. In
      addition, there is emerging evidence that these agents only partially block
      mTORC1, underscoring the need for more effective mTOR inhibitors. In recent
      years, catalytic mTOR inhibitors have been developed, which block both mTORC1 and
      mTORC2. Such inhibitors show generally better activity in preclinical models than
      rapalogs and some of them have been or are in clinical trials in humans. EXPERT
      OPINION: It is anticipated that with the continuous expansion of work in this
      research field, the therapeutic potential of targeting the mTOR pathway for the
      treatment of several malignancies will reach a maximum point in the next few
      years and may ultimately change the way we treat several malignant tumors.

PMID- 23544841
TI  - Inherently multimodal nanoparticle-driven tracking and real-time delineation of
      orthotopic prostate tumors and micrometastases.
AB  - Prostate cancer is the most common cancer among men and the second cause of male
      cancer-related deaths. There are currently three critical needs in prostate
      cancer imaging to personalize cancer treatment: (1) accurate intraprostatic
      imaging for multiple foci and extra-capsular extent; (2) monitoring local and
      systemic treatment response and predicting recurrence; and (3) more sensitive
      imaging of occult prostate cancer bone metastases. Recently, our lab developed
      porphysomes, inherently multimodal, all-organic nanoparticles with flexible and
      robust radiochemistry. Herein, we validate the first in vivo application of
      (64)Cu-porphysomes in clinically relevant orthotopic prostate and bony metastatic
      cancer models. We demonstrate clear multimodal delineation of orthotopic tumors
      on both the macro- and the microscopic scales (using both PET and fluorescence)
      and sensitively detected small bony metastases (<2 mm). The unique and
      multifaceted properties of porphysomes offers a promising all-in-one prostate
      cancer imaging agent for tumor detection and treatment response/recurrence
      monitoring using both radionuclide- and photonic-based strategies.

PMID- 23544842
TI  - Resistin in mid-trimester amniotic fluid in trisomy 21.
AB  - OBJECTIVE: The aim of this study was to examine whether resistin is present in
      second trimester amniotic fluid from trisomy 21 (also known as Down's syndrome)
      pregnancies and whether its concentration differs compared with euploid
      pregnancies. METHODS: The study cohort consisted of 58 women in the mid-trimester
      of pregnancy who underwent amniocentesis for prenatal diagnosis, 31 of whom
      carried a single fetus with diagnosed trisomy 21 (study group) and the rest with
      normal karyotype (control group, n = 27). Groups were matched for maternal and
      gestational age. Levels of resistin in amniotic fluid were measured by a
      commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS:
      Resistin was detected in all amniotic fluid samples. Its median concentration in
      the second trimester amniotic fluid of trisomy 21 pregnancies (2.1 ng/ml) was
      statistically significantly lower (p value <0.001) in comparison with that in
      euploid pregnancies (3.3 ng/ml). CONCLUSIONS: Resistin is a physiologic
      constituent of second trimester amniotic fluid. Lower levels of amniotic fluid
      resistin in pregnancies with trisomy 21 may reflect altered metabolic pathways in
      utero that could possibly be related with phenotypic features of the syndrome.

PMID- 23544843
TI  - Zona pellucida birefringence and meiotic spindle visualisation of human oocytes
      are not influenced by IVM technology.
AB  - The aim of the present study was to investigate the relationship between the
      presence of the meiotic spindle and zona pellucida (ZP) birefringence with
      morphology of in vivo- and in vitro-matured human oocytes. Germinal vesicles
      (n=47) and MI (n=38) oocytes obtained from stimulated ovaries of patients
      undergoing intracytoplasmic sperm injection (ICSI) underwent IVM. Using a
      PolScope (OCTAX PolarAID; Octax, Herbon, Germany), the presence of spindles and
      ZP birefringence was assessed in both in vivo-matured (n=56) and IVM (n=56)
      oocytes. In addition, the morphology of each matured oocyte was evaluated
      microscopically. There were insignificant differences for ZP birefringence and
      meiotic spindle between the in vivo-matured and IVM MII oocytes. Subanalysis
      revealed that the rates of morphologically abnormal oocytes did not differ
      significantly between the two groups, except in the case of irregular shape
      (P=0.001), refractile body (P=0.001) and fragmented polar body (P=0.03), which
      were higher in IVM oocytes. In the case of in vivo-matured oocytes, a
      significantly higher percentage of oocytes with intracytoplasmic and both intra-
      and extracytoplasmic abnormalities have a low birefringent ZP (P=0.007 and
      P=0.02, respectively). There was no relationship between morphological
      abnormalities and spindle detection. The findings suggest that clinical IVM is a
      safe technology that maintains the high maturation rate and integrity of oocytes.
      In addition, the use of the non-invasive PolScope is recommended for the
      detection of oocytes most suitable for ICSI. 

PMID- 23544844
TI  - A comprehensive mathematical model for three-body binding equilibria.
AB  - Three-component systems are often more complex than their two-component
      counterparts. Although the reversible association of three components in solution
      is critical for a vast array of chemical and biological processes, no general
      physical picture of such systems has emerged. Here we have developed a general,
      comprehensive framework for understanding ternary complex equilibria, which
      relates directly to familiar concepts such as EC50 and IC50 from simpler (binary
      complex) equilibria. Importantly, application of our model to data from the
      published literature has enabled us to achieve new insights into complex systems
      ranging from coagulation to therapeutic dosing regimens for monoclonal
      antibodies. We also provide an Excel spreadsheet to assist readers in both
      conceptualizing and applying our models. Overall, our analysis has the potential
      to render complex three-component systems--which have previously been
      characterized as "analytically intractable"--readily comprehensible to
      theoreticians and experimentalists alike.

PMID- 23544845
TI  - Acupuncture adverse events in China: a glimpse of historical and contextual
      aspects.
AB  - The article by He and colleagues, "Adverse Events Following Acupuncture: A
      Systematic Review of the Chinese Literature for the Years 1956-2010" is an
      important and timely contribution. In this commentary, the article is reviewed
      and issues are highlighted about how to interpret and contextualize the results
      of their study. While their review has been well performed, certain areas have
      been identified where the results may be inaccurate due to problems in the
      reporting of original incidents. For example, potential problems were found in
      the reporting of the minor adverse event (AE) of fainting and the more serious
      AEs of pneumothorax and hepatitis. The article by He and colleagues highlights
      the issue that almost all AEs associated with acupuncture in the modern period
      are due to the administration of the therapy rather than the therapy itself.
      Future prospective studies can address some of the shortcomings identified in
      this review.

PMID- 23544846
TI  - Optoelectronic and ferroelectric properties of cerium-doped
      (Na(0.5)Bi(0.5))(Ti(0.99)Fe(0.01))O3 nanocrystalline films on (111)
      Pt/TiO2/SiO2/Si: a composition-dependent study.
AB  - The optical and ferroelectric properties of (Na0.5Bi0.5)1-xCex(Ti0.99Fe0.01)O3
      (NBCTFx; 0 <= x <= 0.10) nanocrystalline films deposited on platinized silicon
      (Pt/TiO2/SiO2/Si) substrates using a sol-gel method were investigated. The
      microstructure, surface, and cross-sectional morphology and compositions of the
      films were analyzed by X-ray diffraction, scanning electron microscopy, and X-ray
      photoelectron spectroscopy, respectively. The X-ray diffraction patterns indicate
      that all films are polycrystalline and show the single perovskite structure. The
      dielectric functions of the NBCTFx films can be uniquely extracted by fitting the
      measured ellipsometric spectra with a four-phase-layered model (air/surface rough
      layer/NBCTFx/Pt) in the photon energy range of 0.6-6.4 eV. The Tauc-Lorentz model
      was successfully applied and reasonably describes the spectral response behavior
      of ferroelectric NBCTFx films in the light-frequency region. It was found that
      the optical band gap and grain size decrease with increasing cerium composition
      because of the introduction of disorder and defects. The electrical results show
      that the leakage current density of the films was decreased with increasing
      cerium composition by reducing the density of oxygen vacancies and forming the
      defect complexes. The optimal ferroelectric properties were obtained in the film
      doped with x = 0.10, whose remnant polarization and coercive field values are
      14.9 MUC/cm(2) and 217.3 kV/cm, respectively. The present results could be
      crucial for future applications of lead-free ferroelectric and optoelectronic
      devices.

PMID- 23544847
TI  - Comment on "Assessment and validation of density functional approximations for
      iron carbide and iron carbide cation".

PMID- 23544848
TI  - Nanocolloidal carriers of isotretinoin: antimicrobial activity against
      Propionibacterium acnes and dermatokinetic modeling.
AB  - Acne, a common skin disease in teenagers, is caused by Propionibacterium acnes
      (P. acnes). Isotretinoin (ITR) is though reported to have immense antiacne
      potential, yet there are hardly any reports vouching its antimicrobial activity.
      The present study, therefore, was undertaken to study the antimicrobial activity
      of ITR and evaluate the effect of its encasement in nanocarriers on its minimum
      inhibitory concentration (MIC). The nanocarriers were also evaluated for the skin
      transport characteristics. MICs of pure drug and entrapped drug in nanolipid
      carriers (ITR-NLCs) and in solid lipid nanoparticles (ITR-SLNs) were determined
      by broth dilution method against clindamycin phosphate as the reference
      antibiotic. It was observed that ITR possessed marked antimicrobial activity
      against anaerobic pathogen, P. acnes. Nanocarriers loaded with ITR, that is, SLNs
      and NLCs, enhanced the antimicrobial activity even at lower concentrations vis-a
      vis the drug alone and improved drug transport potential vis-a-vis the commercial
      gel. The unique findings could be the result of effective adhesion of ITR-loaded
      nanocarriers to the bacterial membranes and release of drug directly to the
      target. Besides establishing ITR as an antimicrobial agent against acne-causing
      bacteria, the current work ratifies immense potential of nanocolloidal carriers
      like SLNs and NLCs to treat acne in a more efficient manner.

PMID- 23544849
TI  - Trypanosoma cruzi genotyping supports a common source of infection in a school
      related oral outbreak of acute Chagas disease in Venezuela.
AB  - Trypanosoma cruzi I, a discrete typing unit (DTU) found in human infections in
      Venezuela and other countries of the northern region of South America and in
      Central America, has been recently classified into five intra-DTU genotypes (Ia,
      Ib, Ic, Id, Ie) based on sequence polymorphisms found in the spliced leader
      intergenic region. In this paper we report the genotype identification of T.
      cruzi human isolates from one outbreak of acute orally acquired Chagas disease
      that occurred in a non-endemic region of Venezuela and from T. cruzi triatomine
      and rat isolates captured at a guava juice preparation site which was identified
      as the presumptive source of infection. The genotyping of all these isolates as
      TcId supports the view of a common source of infection in this oral Chagas
      disease outbreak through the ingestion of guava juice. Implications for clinical
      manifestations and dynamics of transmission cycles are discussed.

PMID- 23544851
TI  - Specific phosphorylation of the PfRh2b invasion ligand of Plasmodium falciparum.
AB  - Red blood cell invasion by the malaria parasite Plasmodium falciparum relies on a
      complex protein network that uses low and high affinity receptor-ligand
      interactions. Signal transduction through the action of specific kinases is a
      control mechanism for the orchestration of this process. In the present study we
      report on the phosphorylation of the CPD (cytoplasmic domain) of P. falciparum
      Rh2b (reticulocyte homologue protein 2b). First, we identified Ser3233 as the
      sole phospho-acceptor site in the CPD for in vitro phosphorylation by parasite
      extract. We provide several lines of evidence that this phosphorylation is
      mediated by PfCK2 (P. falciparum casein kinase 2): phosphorylation is cAMP
      independent, utilizes ATP as well as GTP as phosphate donors, is inhibited by
      heparin and tetrabromocinnamic acid, and is mediated by purified PfCK2. We raised
      a phospho-specific antibody and showed that Ser3233 phosphorylation occurs in the
      parasite prior to host cell egress. We analysed the spatiotemporal aspects of
      this phosphorylation using immunoprecipitated endogenous Rh2b and minigenes
      expressing the CPD either at the plasma or rhoptry membrane. Phosphorylation of
      Rh2b is not spatially restricted to either the plasma or rhoptry membrane and
      most probably occurs before Rh2b is translocated from the rhoptry neck to the
      plasma membrane.

PMID- 23544852
TI  - Response to sorafenib in a pediatric patient with papillary thyroid carcinoma
      with diffuse nodular pulmonary disease requiring mechanical ventilation.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) presents with local and distant
      metastases more frequently in children than in adults. However, hypoxemia
      secondary to pulmonary metastases has not been reported in the literature.
      Sorafenib is a small-molecule multikinase inhibitor used in radioactive iodine
      ((131)I)-refractive papillary thyroid carcinoma. PATIENT FINDINGS: An eight-year
      old boy presented with fever and hypoxemia and was found to have H1N1 viral
      pneumonia requiring mechanical ventilation and antiviral and glucocorticoid
      treatment. After initial improvement, he was readmitted one month later because
      of persistent hypoxemia. A high-resolution computed tomography of the chest and
      neck revealed multiple 1-4 mm nodules and necrotic lymph nodes on the right side
      of the neck. Left lung wedge resection and right deep cervical node biopsies were
      consistent with PTC. He underwent a total thyroidectomy with a central neck node
      dissection and postoperatively required prolonged mechanical ventilation. Due to
      the inability to be weaned from mechanical ventilation, treatment with sorafenib
      200 mg daily (10 mg/kg/day, 250 mg/m(2)) was initiated. Eight days thereafter,
      ventilation support was discontinued and the child was extubated. However, he
      failed extubation secondary to supraglottic edema, and seven days later
      tracheostomy was performed. The dosage of sorafenib was increased to 200 mg twice
      daily (20 mg/kg/day, 500 mg/m(2)). After 52 days of therapy, a repeat computed
      tomography scan showed reduction in the lung nodule size to 1-2 mm. He underwent
      (131)I therapy 87 days after sorafenib was started. A post-treatment scan showed
      extensive uptake throughout the lungs and thyroid bed, supraclavicular nodes, and
      cervical nodes. CONCLUSIONS: This is the first reported case of a pediatric
      patient with respiratory failure possibly secondary to diffuse micronodular PTC
      requiring mechanical ventilation and subsequent delay in definitive therapy.
      Sorafenib could be considered for gap therapy when (131)I therapy cannot be
      administered in a timely manner. Treatment with this multikinase inhibitor does
      not seem to adversely affect the uptake of (131)I in radiation-naive patients.

PMID- 23544853
TI  - Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese
      rats.
AB  - BACKGROUND: Studies investigating the effects of dipeptidyl peptidase-4
      inhibitors on hepatic steatosis are lacking. We aimed to determine the effects of
      sitagliptin on nonalcoholic fatty liver disease (NAFLD) in rats with diet-induced
      obesity. METHODS: A total of 24 adult female Sprague-Dawley rats, which were 24
      weeks old and weighed 199-240 grams, were used. The rats were randomly separated
      into two groups. The control group (n=6) was fed with standard rat diet; the
      remaining rats (n=18) were fed with a high-fat diet (HFD) to induce NAFLD. After
      12 weeks, rats that were fed with a HFD were randomly separated into two groups:
      (1) HFD-only group (n=8) was fed with a HFD for an additional 4 weeks, (2) HFD
      sitagliptin group (n=10) received sitagliptin (3 mg/kg) for 4 weeks in addition
      to HFD. At the end of the study (16(th) week), blood samples were drawn from all
      rats to determine serum glucose, triglyceride, cholesterol, alanine
      aminotransferase (ALT), and plasma insulin levels. Insulin resistance was
      determined using the homeostasis model assessment of insulin resistance (HOMA-IR)
      index. Histopathologic evaluation of liver samples was undertaken. RESULTS: The
      HFD-sitagliptin group had significantly lower serum glucose (140.8+/-18.8 vs.
      224.7+/-20.6 mg/dL, P<0.001), plasma insulin (15.8+/-4.4 vs. 28.0+/-5.9 MUIU/L,
      P<0.001), HOMA-IR index (4.9+/-1.8 vs. 15.9+/-2.3, P<0.001), serum triglycerides
      (199.0+/-108.7 vs. 468.0+/-370.7 mg/dL, P<0.001), and cholesterol (82.0+/-26.7
      vs. 90.5+/-7.0, P<0.001) values compared to the HFD-only group. Hepatic steatosis
      was significantly less (mean score, 1 vs. 2; P<0.001) in the HFD-sitagliptin
      group compared to the HFD-only group, whereas there was no difference in hepatic
      inflammation (P=0.057), liver weight (P=0.068), and ALT levels (P=0.232).
      CONCLUSION: Sitagliptin may improve hepatic steatosis by increasing insulin
      sensitivity and improving lipid profiles in rats.

PMID- 23544854
TI  - Developmental and gender related differences in response switches after
      nonrepresentative negative feedback.
AB  - In many decision making tasks negative feedback is probabilistic and, as a
      consequence, may be given when the decision is actually correct. This feedback
      can be referred to as nonrepresentative negative feedback. In the current study,
      we investigated developmental and gender related differences in such switching
      after nonrepresentative negative feedback. Participants performed a new
      probabilistic negative feedback task in which properties of choice options were
      known to the participants; therefore, they did not have to learn the correct
      response. The task was administered to a developmental sample between 8 and 16
      years of age (N = 170). Results indicated that switching after nonrepresentative
      negative feedback decreased with age and that this switching was more pronounced
      in females than in males. We discuss results in light of an imbalance between
      emotional and inhibition systems and tentatively conclude that it is likely that
      the age related differences are predominantly related to the strength of the
      inhibition system, whereas the gender related differences are predominantly
      related to the strength of the emotional system.

PMID- 23544855
TI  - Evaluations of and reasoning about normative and deviant ingroup and outgroup
      members: development of the black sheep effect.
AB  - Research with adults has demonstrated a "black sheep effect" (BSE) whereby,
      relative to evaluations of normative group members, ingroup deviants are
      derogated more than outgroup deviants. The developmental subjective group
      dynamics (DSGD) model holds that the BSE should develop during middle childhood
      when children apply wider social norms. Three hundred and thirty-eight children
      who were between 5 and 12 years old judged a normative (socially desirable) and a
      deviant (socially undesirable) member from an ingroup or an outgroup school.
      Results confirmed a developmental increase in the BSE, the first time this has
      been demonstrated. Children's own evaluations of group members were mediated by
      their expectations about ingroup peers' evaluations. In line with DSGD and social
      domain theories, with age, children's explanations of peer evaluations for
      ingroup deviance focused relatively more on loyalty. Practical and theoretical
      implications for peer inclusion and exclusion are discussed.

PMID- 23544856
TI  - Deafness, thought bubbles, and theory-of-mind development.
AB  - The processes and mechanisms of theory-of-mind development were examined via a
      training study of false-belief conceptions in deaf children of hearing parents (N
      = 43). In comparison to 2 different control conditions, training based on thought
      bubble instruction about beliefs was linked with improved false-belief
      understanding as well as progress on a broader theory-of-mind scale. By combining
      intervention, microgenetic, and developmental scaling methods, the findings
      provide informative data about the nature and mechanisms of theory-of-mind change
      in deaf children, as well as an initial demonstration of a useful intervention
      for enhancing social cognition in deaf children of hearing parents. The methods
      and results also point to possible avenues for the study of conceptual change
      more generally.

PMID- 23544857
TI  - Development of planning abilities in normal aging: differential effects of
      specific cognitive demands.
AB  - In line with the frontal hypothesis of aging, the ability to plan ahead undergoes
      substantial change during normal aging. Although impairments on the Tower of
      London planning task were reported earlier, associations between age-related
      declines and specific cognitive demands on planning have not been studied. Here
      we investigated the impact of search depth and goal ambiguity on planning, which
      impose demands on the depth and breadth of look-ahead processes, respectively.
      Besides an overall age-related decline in planning accuracy of 106 healthy older
      adults, differential search depth effects were found: Whereas planning accuracy
      of subjects in the early 60s was not affected by variations in search depth,
      between the ages of 65 and 76 years, accuracy was significantly decreased for
      high versus low levels of search depth. For subjects older than 76, different
      search depth levels did not further impact on accuracy, which was lowest overall.
      This nonlinear pattern may reflect differential impairments in fluid abilities
      and working memory capacity across various stages of older age. As no age-related
      effects of goal ambiguity were found, normal aging seems to be specifically
      sensitive to planning demands on the depth but not the breadth of anticipatory
      search processes. Hence, cognitive functions subserved by the prefrontal cortex
      experience differential development over the course of normal aging.

PMID- 23544858
TI  - Modeling socioeconomic status effects on language development.
AB  - Socioeconomic status (SES) is an important environmental predictor of language
      and cognitive development, but the causal pathways by which it operates are
      unclear. We used a computational model of development to explore the adequacy of
      manipulations of environmental information to simulate SES effects in English
      past-tense acquisition, in a data set provided by Bishop (2005). To our
      knowledge, this is the first application of computational models of development
      to SES. The simulations addressed 3 new challenges: (a) to combine models of
      development and individual differences in a single framework, (b) to expand
      modeling to the population level, and (c) to implement both environmental and
      genetic/intrinsic sources of individual differences. The model succeeded in
      capturing the qualitative patterns of regularity effects in both population
      performance and the predictive power of SES that were observed in the empirical
      data. The model suggested that the empirical data are best captured by relatively
      wider variation in learning abilities and relatively narrow variation in (and
      good quality of) environmental information. There were shortcomings in the
      model's quantitative fit, which are discussed. The model made several novel
      predictions, with respect to the influence of SES on delay versus giftedness, the
      change of SES effects over development, and the influence of SES on children of
      different ability levels (gene-environment interactions). The first of these
      predictions was that SES should reliably predict gifted performance in children
      but not delayed performance, and the prediction was supported by the Bishop data
      set. Finally, the model demonstrated limits on the inferences that can be drawn
      about developmental mechanisms on the basis of data from individual differences.

PMID- 23544859
TI  - Effective coviewing: Preschoolers' learning from video after a dialogic
      questioning intervention.
AB  - Young preschoolers rapidly acquire new information from social partners but do
      not learn efficiently from people on video. We trained parents to use
      Whitehurst's dialogic reading questioning techniques while watching educational
      television with their children. Eighty-one parents coviewed storybook videos with
      their 3-year-old children in 1 of 4 conditions: dialogic questioning (pause, ask
      questions, and encourage children to tell parts of the story), directed attention
      (pause and comment but do not ask questions), dialogic actress (show the videos
      with dialogic questioning by an on-screen actress embedded in them), or no
      intervention (show the videos as usual). After 4 weeks, children in the dialogic
      questioning group scored higher than children in the directed attention and no
      intervention groups on story comprehension and story vocabulary measures. Scores
      from the dialogic actress group fell in between. On a standardized measure of
      expressive vocabulary, children in the 2 parent-interaction groups exhibited
      significant improvement over their pretest scores. Results indicate that parent
      led questioning enhances children's learning from video stories at age 3 and that
      a video incorporating an on-screen dialogic questioner may also be effective.
      Mechanisms behind the effect of dialogic reading-style interventions are
      discussed.

PMID- 23544860
TI  - Acting on observed social exclusion: Developmental perspectives on punishment of
      excluders and compensation of victims.
AB  - This study examined punishment of excluders and compensation of victims after
      observing an instance of social exclusion at various phases of adolescent
      development. Participants (n = 183; age 9 to 22 years) were first included in a
      virtual ball-tossing game, Cyberball, and then observed the exclusion of a peer.
      Subsequently, they played economic games in which they divided money between
      themselves and the including players, the excluders, and the victim. The results
      demonstrate a gradual age-related increase in money given to the victim from age
      9 to 22 and a gradual decrease in money allocated to the excluders from age 9 to
      16 with an increase in 22-year-olds. Affective perspective-taking predicted both
      compensation of the victim and punishment of the excluders. Taken together these
      results show that across adolescence individuals sacrifice an increasingly bigger
      share of their own resources to punish excluders and to compensate victims and
      that taking the perspective of the victim enhances these decisions.

PMID- 23544861
TI  - Quantitative understanding of guest binding enables the design of complex host
      guest behavior.
AB  - We report a detailed binding study addressing both the thermodynamics and
      kinetics of binding of a large set of guest molecules with widely varying
      properties to a water-soluble M4L6 metal-organic host. The effects of different
      guest properties upon the binding strength and kinetics were elucidated by a
      systematic analysis of the binding data through principal component analysis,
      thus allowing structure-property relationships to be determined. These insights
      enabled us to design more complex encapsulation sequences in which multiple
      guests that were added simultaneously were bound and released by the host in a
      time-dependent manner, thus allowing multiple states of the system to be accessed
      sequentially. Moreover, by inclusion of the pH-sensitive guest pyridine, we were
      able to further extend our control over the binding by creating a reversible pH
      controlled three-guest sequential binding cycle.

PMID- 23544862
TI  - Umbilical artery Doppler in relation to placental pathology and FV Leiden in
      pregnant women and their offspring.
AB  - OBJECTIVE: Abnormal umbilical artery blood flow has been implicated in pregnancy
      complications and fetal demise. Its relation to histopathological changes in the
      placenta and to maternal or fetal thrombophilia is less well understood. The aim
      of this study was to evaluate the relation between umbilical artery Doppler
      findings, placental histopathology, and maternal and fetal coagulation factor V
      Leiden (FVL) status. METHODS: Two previous studies on FVL in pregnancy made the
      placentas of 25 women with maternal FVL carriership and 43 randomly selected non
      carriers available for a histopathological examination. Umbilical artery Doppler
      velocimetry was performed on 54 women in late pregnancy. RESULTS: Abnormal
      umbilical artery Doppler velocimetry was associated with an approximately
      sevenfold increased risk of fetoplacental thrombotic vasculopathy (odds ratio
      [OR]: 7.5, 95% confidence intervals [CI]: 1.3-44.3), ischemic lesions (OR: 7.5,
      95% CI: 1.2-46.1) and fetal carriership of FVL (OR: 8.2, 95% CI: 1.5-43.5), but
      not maternal FVL. Fetal FVL carriership was also associated with a sevenfold
      increased risk of ischemic lesions (OR: 6.7, 95% CI: 1.3-35). CONCLUSIONS: Our
      results indicate that the fetal - not the maternal - FVL carriership matters
      regarding the umbilical artery blood flow and placental pathology, which might
      explain some of the heterogeneity of studies.

PMID- 23544864
TI  - Clay-based nanocomposite coating for flexible optoelectronics applying commercial
      polymers.
AB  - Transparency, flexibility, and especially ultralow oxygen (OTR) and water vapor
      (WVTR) transmission rates are the key issues to be addressed for packaging of
      flexible organic photovoltaics and organic light-emitting diodes. Concomitant
      optimization of all essential features is still a big challenge. Here we present
      a thin (1.5 MUm), highly transparent, and at the same time flexible nanocomposite
      coating with an exceptionally low OTR and WVTR (1.0 * 10(-2) cm(3) m(-2) day(-1)
      bar(-1) and <0.05 g m(-2) day(-1) at 50% RH, respectively). A commercially
      available polyurethane (Desmodur N 3600 and Desmophen 670 BA, Bayer
      MaterialScience AG) was filled with a delaminated synthetic layered silicate
      exhibiting huge aspect ratios of about 25,000. Functional films were prepared by
      simple doctor-blading a suspension of the matrix and the organophilized clay.
      This preparation procedure is technically benign, is easy to scale up, and may
      readily be applied for encapsulation of sensitive flexible electronics.

PMID- 23544865
TI  - A review of contraceptive practices among married and unmarried women in China
      from 1982 to 2010.
AB  - OBJECTIVE: To analyse the contraceptive prevalence rate (CPR) among - and
      contraceptive methods used by - married and unmarried women in China, from 1982
      to 2010. METHOD: Data concerning married women were collected from national
      surveys conducted by the Chinese government. Those pertaining to unmarried women
      were obtained by searching the China Academic Journal Network Publishing database
      and PubMed. RESULTS: CPR among married women in China was 89% in 2010, the
      highest in the world. Most married women use long-acting reversible
      contraceptives, particularly intrauterine devices, and sterilisation. CPR among
      sexually active unmarried women has fluctuated between 17 and 70% since 1988,
      although the frequency of condom use has increased (Cochran-Armitage trend test,
      chi(2) = 126.1, p < 0.001). More than 25% of unmarried women rely since at least
      1982 on less effective contraceptive methods, including rhythm and withdrawal.
      This has led to an annual induced abortion rate of approximately 20% among those
      women. CONCLUSION: In sharp contrast to the high CPR among married women, the
      rate among sexually active unmarried women in China has remained extremely low
      since 1988. More efforts should be directed at raising contraception awareness
      among this population to improve their reproductive health and reduce the rate of
      unwanted pregnancy.

PMID- 23544868
TI  - Alternating sites reactivity is a common feature of thiamin diphosphate-dependent
      enzymes as evidenced by isothermal titration calorimetry studies of substrate
      binding.
AB  - Thiamin diphosphate (ThDP)-dependent enzymes play vital roles in cellular
      metabolism in all kingdoms of life. In previous kinetic and structural studies, a
      communication between the active centers in terms of a negative cooperativity had
      been suggested for some but not all ThDP enzymes, which typically operate as
      functional dimers. To further underline this hypothesis and to test its
      universality, we investigated the binding of substrate analogue methyl
      acetylphosphonate (MAP) to three different ThDP-dependent enzymes acting on
      substrate pyruvate, namely, the Escherichia coli E1 component of the pyruvate
      dehydrogenase complex, E. coli acetohydroxyacid synthase isoenzyme I, and the
      Lactobacillus plantarum pyruvate oxidase using isothermal titration calorimetry.
      The results unambiguously show for all three enzymes studied that only one active
      center of the functional dimers accomplishes covalent binding of the substrate
      analogue, supporting the proposed alternating sites reactivity as a common
      feature of all ThDP enzymes and resolving the recent controversy in the field.

PMID- 23544869
TI  - Phosphino-boryl-naphthalenes: geometrically enforced, yet Lewis acid responsive P
      -> B interactions.
AB  - Three naphthyl-bridged phosphine-borane derivatives 2-BCy2, 2-BMes2, and 2-BFlu,
      differing in the steric and electronic properties of the boryl moiety, have been
      prepared and characterized by spectroscopic and crystallographic means. The
      presence and magnitude of the P -> B interactions have been assessed
      experimentally and theoretically. The naphthyl linker was found to enforce the P 
      > B interaction despite steric shielding, while retaining enough flexibility to
      respond to the Lewis acidity of boron.

PMID- 23544871
TI  - HUVEC biocompatibility and platelet activation of segmented polyurethanes
      prepared with either glutathione or its amino acids as chain extenders.
AB  - Novel biodegradable segmented polyurethanes (SPUs) were synthesized with
      polycaprolactone diol, 4,4'-methylen bis (cyclohexyl isocyanate) (HMDI), and
      either L-glutathione or its constituent amino acids (L-glutamic acid, L-cysteine
      and glycine) as chain extenders. Fourier transform infrared spectroscopy analysis
      revealed the feasibility of obtaining polyurethanes through the presence of NH
      (Amide II), C-N, C-O, and C=O bands and the absence of NCO band. Differential
      scanning calorimetry and X-ray diffraction revealed that a semicrystalline
      polymer (T m = 42-52  degrees C; 2theta = 21.3 degrees  and 23 degrees ) was
      obtained in all cases, while dynamic mechanical analysis (DMA) revealed an
      amorphous phase (T g = -30 to -36 (o)C). These properties, in addition to their
      high molecular weight, led to high moduli and higher extensibilities when glycine
      and glutamic acid were used as chain extenders. Clotting times (Lee-White test)
      and activated partial thromboplastin time determined on these polyurethanes were
      longer than with glass. In addition, all synthesized SPU exhibited platelet
      activation indexes below the collagen type I positive control. Human umbilical
      vein endothelial cells viability was higher in SPUs containing either glycine or
      cysteine. The obtained results indicate that SPUs that use cysteine as chain
      extender are promising candidates for cardiovascular applications. 

PMID- 23544872
TI  - A noninvasive encapsulated macrofollicular variant of papillary thyroid carcinoma
      presenting with gross lymph node metastasis: a case report and literature review.

PMID- 23544870
TI  - Antisense oligonucleotides for the treatment of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting ~1 in
      10,000 live births. The most striking component is the loss of alpha-motor
      neurons in the ventral horn of the spinal cord, resulting in progressive
      paralysis and eventually premature death. There is no current treatment paradigm
      other than supportive care, though the past 15 years has seen a striking
      advancement in understanding of both SMA genetics and molecular mechanisms. A
      variety of disease-modifying interventions are rapidly bridging the translational
      gap from the laboratory to clinical trials, including the application of
      antisense oligonucleotide (ASO) therapy for the correction of aberrant RNA
      splicing characteristic of SMA. Survival motor neuron (SMN) is a ubiquitously
      expressed 38-kD protein. Humans have two genes that produce SMN, SMN1 and SMN2,
      the former of which is deleted or nonfunctional in the majority of patients with
      SMA. These two genes are nearly identical with one exception, a C to T transition
      (C6T) within exon 7 of SMN2. C6T disrupts a modulator of splicing, leading to the
      exclusion of exon 7 from ~90% of the mRNA transcript. The resultant truncated
      Delta7SMN protein does not oligomerize efficiently and is rapidly degraded. SMA
      can therefore be considered a disease of too little SMN protein. A number of cis
      acting splice modifiers have been identified in the region of exon 7, the steric
      block of which enhances the retention of the exon and a resultant full-length
      mRNA sequence. ASOs targeted to these splice motifs have shown impressive
      phenotype rescue in multiple SMA mouse models.

PMID- 23544873
TI  - Cognitive predictors for five-year conversion to dementia in community-dwelling
      Chinese older adults.
AB  - BACKGROUND: This study evaluates which cognitive measure is best for predicting
      incident dementia in a population-based random sample of Chinese older adults
      without dementia over a five-year period. METHODS: A total of 787 community
      dwelling Chinese older adults without dementia in Hong Kong were assessed at
      baseline (T0), at two years (T1), and at five years (T2). RESULTS: The annual
      conversion rate to dementia was 1.6% and 6.3% for baseline normal participants
      and baseline mild cognitive impairment (MCI) participants, respectively. The
      Cantonese version of Mini-mental State Examination (CMMSE) scores declined
      significantly over time. In participants who progressed to dementia, Category
      Verbal Fluency Test (CVFT) scores dropped significantly from T0 to T1. A 1-SD
      drop of either CMMSE or CVFT in two years predicted dementia at five years with
      91.5% sensitivity and 62.0% specificity. A stable CMMSE and CVFT at two years
      predicted a 91% chance of not progressing to clinical dementia at five years.
      CONCLUSION: In this community sample of Chinese older adults, a decline in
      cognitive screening tests in short term (two years) offered useful information in
      predicting dementia conversion over a longer period.

PMID- 23544874
TI  - Synthesis and enhanced lithium storage properties of electrospun V2O5 nanofibers
      in full-cell assembly with a spinel Li4Ti5O12 anode.
AB  - We have successfully demonstrated the reversible electrochemical Li-insertion
      properties of electrospun vanadium pentoxide nanofibers (VNF) in full-cell
      assembly with a Li4Ti5O12 anode. Li-insertion in to VNF is restricted for the
      intercalation of 1 mol of Li by adjusting lower cutoff potential (2.5-4 V vs Li).
      The half-cell (Li/VNF) delivered a reversible capacity of ~148 mA h g(-1) with
      excellent cycleability and capacity retention of over 85% after 30 cycles. Full
      cell assembly is conducted for such VNF cathodes after the electrochemical
      lithiation (LiV2O5) with spinel Li4Ti5O12 anode under the optimized mass
      loadings. Full-cell (LiV2O5/Li4Ti5O12) delivered an excellent cycleability
      irrespective of applied current densities with good reversible capacity of ~119
      mA h g(-1) (at 20 mA g(-1) current density). This work clearly demonstrates the
      possibility of using LiV2O5/Li4Ti5O12 configuration for high power applications
      such as hybrid electric vehicles and electric vehicles in the near future.

PMID- 23544878
TI  - Evaluation of the degradation of clonidine-loaded PLGA microspheres.
AB  - CONTEXT: The release of an encapsulated drug is dependent on diffusion and/or
      degradation/erosion processes. OBJECTIVE: This work aimed to better understand
      the degradation mechanism of clonidine-loaded microparticles. METHODS: Gel
      permeation chromatography was used to evaluate the degradation of the polymer.
      The water-uptake and the weight loss were determined gravimetrically. The
      swelling behaviour and the morphological changes of the formulations were
      observed by microscopy. The glass transition temperature and the crystallinity
      were also determined by differential scanning calorimetry and X-ray diffraction,
      respectively. The pH of the medium and inside the microspheres was assessed.
      RESULTS: The microspheres captured a large amount of water, allowing a decrease
      in the molecular weight of the polymer. The pH of the medium decreased after
      release of the degradation products and the pH inside the microparticles remained
      constant due to the neutralization of these acidic products. CONCLUSION:
      Clonidine and buffers both had an action on the degradation.

PMID- 23544877
TI  - Biodistribution and pharmacokinetics of EGFR-targeted thiolated gelatin
      nanoparticles following systemic administration in pancreatic tumor-bearing mice.
AB  - The objective of this study was to evaluate qualitative and quantitative
      biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated
      type B gelatin nanoparticles in vivo in subcutaneous human pancreatic
      adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted
      nanoparticles showed preferential and sustained accumulation in the tumor mass,
      especially at early time points. Higher blood concentrations and higher tumor
      accumulations were observed with PEG-modified and EGFR-targeted nanoparticles
      during the study (AUClast: 17.38 and 19.56%ID/mL.h in blood, 187 and 322%ID/g.h
      in tumor for PEG-modified and EGFR-targeted nanoparticles, respectively), as
      compared to control, unmodified particles (AUClast: 10.71%ID/mL.h in blood and
      138%ID/g.h in tumor). EGFR-targeted nanoparticles displayed almost twice tumor
      targeting efficiency than either PEG-modified or the unmodified nanoparticles,
      highlighting the efficacy of the active targeting strategy. In conclusion, this
      study shows that EGFR-targeted and PEG-modified nanoparticles were suitable
      vehicles for specific systemic delivery in subcutaneous Panc-1 tumor xenograft
      models.

PMID- 23544879
TI  - Wheat germ agglutinin-functionalised crosslinked polyelectrolyte microparticles
      for local colon delivery of 5-FU: in vitro efficacy and in vivo gastrointestinal
      distribution.
AB  - We have previously reported the development and characterisation of wheat germ
      agglutinin (WGA)-functionalised chitosan-Ca-alginate (CTS-Ca-ALG) microparticles
      (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU). In the
      present work, our goal was to evaluate the potential of these carriers for
      efficient treatment of colon cancer by studying in vitro permeability and cell
      association of 5-FU and [methyl-3H]thymidine uptake in Caco-2 cells, as well as
      in vivo gastrointestinal distribution. The amount of 5-FU permeated through Caco
      2 cells was 15.1, 7.7 and 6.5% for 5-FU solution, CTS-Ca-ALG MPs and WGA
      conjugates. The concentration of 5-FU associated with Caco-2 cells was
      significantly greater when delivered from MPs. By incorporation of 5-FU into MPs
      and further decoration with WGA, an increased [methyl-3H]thymidine uptake was
      observed few hours after continuous drug treatment followed by significantly
      reduced uptake after 6 h. Gastrointestinal distribution was in favour of
      increased localisation and concentration of the particles in colon region.

PMID- 23544880
TI  - The distribution and functional properties of Pelizaeus-Merzbacher-like disease
      linked Cx47 mutations on Cx47/Cx47 homotypic and Cx47/Cx43 heterotypic gap
      junctions.
AB  - GJs (gap junctions) allow direct intercellular communication, and consist of Cxs
      (connexins). In the mammalian central nervous system, oligodendrocytes express
      Cx47, Cx32 and Cx29, whereas astrocytes express Cx43, Cx30 and Cx26. Homotypic
      Cx47/Cx47 GJs couple oligodendrocytes, and heterotypic Cx47/Cx43 channels are the
      primary GJs at oligodendrocyte/astrocyte junctions. Interestingly, autosomal
      recessive mutations in the gene GJC2 encoding Cx47 have been linked to a central
      hypomyelinating disease termed PMLD (Pelizaeus-Merzbacher-like disease). The aim
      of the present study was to determine the cellular distribution and functional
      properties of PMLD-associated Cx47 mutants (I46M, G149S, G236R, G236S, M286T and
      T398I). Expressing GFP (green fluorescent protein)-tagged mutant versions of Cx47
      in gap-junction-deficient model cells revealed that these mutants were detected
      at the cell-cell interface similar to that observed for wild-type Cx47.
      Furthermore, four of the six mutants showed no electrical coupling in both
      Cx47/Cx47 and Cx47/Cx43 GJ channels. These results suggest that most of the PMLD
      linked Cx47 mutants disrupt Cx47/Cx47 and Cx47/Cx43 GJ function in the glial
      network, which may play a role in leading to PMLD symptoms.

PMID- 23544881
TI  - Efficient tandem and triple-junction polymer solar cells.
AB  - We demonstrate tandem and triple-junction polymer solar cells with power
      conversion efficiencies of 8.9% and 9.6% that use a newly designed, high
      molecular weight, small band gap semiconducting polymer and a matching wide band
      gap polymer.

PMID- 23544882
TI  - Changes of red blood cell rheology in newborns with congenital hypothyroidism
      during treatment.
AB  - AIM: We aimed to evaluate the deformability characteristics of RBC and the
      affecting factors in newborns diagnosed with congenital hypothyroidism (CH) and
      to compare the outcomes after the L-thyroxin treatment. PATIENTS AND METHODS:
      Enrolled subjects were divided into two subgroups as "patients" and age-matched
      healthy "controls". First blood samples were taken from all subjects for
      measuring elongation index (rEI) and osmotic fragility of RBC (OF), hematic and
      biochemical analytes affecting the RBC deformability in the neonatal age. All
      parameters were repeated a month after provided euthyroid state following the
      treatment in patients and age-matched healthy controls. RESULTS: There was no
      difference between both groups in terms of complete blood count parameters and
      serum analytes (albumin, bilirubin and fibrinogen) except expected age-related
      changes in the first and second readings. Serum lipid/lipoprotein levels of both
      groups remained unchanged except triglyceride levels during the study period. The
      rEI of the patients were lower than that of controls in the first and second
      readings. The rEIs of the patients became increased, reaching (not equal) the
      levels of their controls during L-thyroxin treatment. Osmotic fragility of the
      patients was detected as lower than controls in the first and second readings,
      and became better during L-thyroxin treatment. CONCLUSION: Our results indicate
      that some changes may occur on the hematic and biochemical analytes affecting the
      RBC deformability features. Neonates with CH have the worst rEI initially, but
      they reached the indices of the healthy infants thanks to L-thyroxin treatment.
      Also, their OF features have been improved by L-thyroxin.

PMID- 23544883
TI  - Fabrication of three-dimensional carbon nanotube and metal oxide hybrid
      mesoporous architectures.
AB  - Three-dimensional (3D) vertically aligned carbon nanotube (CNT) patterns were
      utilized as templates for fabricating mesoporous hybrid architectures composed of
      CNTs and various crystalline metal oxide (MO; M = Co, Zn, Mn) nanoparticles by a
      microwave-assisted chemical approach. Post-synthesis thermal treatment of the
      CNT/MO patterns culminated in structural reorganization, depending on the
      treatment conditions. In air, CNTs were removed by oxidation. The remaining MO
      architectures preserved the shape and alignment of the original 3D CNT patterns,
      but with different porosity characteristics and improved MO crystallinity.
      Elastocapillary condensation and bending were demonstrated to be useful tools for
      further architecture alternation. The mesoporous nature of the CNT/MO hybrids and
      the MO materials were confirmed by N2-BET measurements. CNT/Co3O4 aligned strips
      were used as an example to demonstrate the potential application of the CNT/MO
      architectures as electrode materials for supercapacitive storage. Galvanostatic
      measurements showed that the CNT/Co3O4 strips were stable up to 1000 charge
      discharge cycles at a current density of 377 MUA/cm(2) with a specific
      capacitance as high as 123.94 F/g.

PMID- 23544886
TI  - Autoreactive bronchus-associated lymphoid tissue in interstitial lung disease:
      friend or foe?

PMID- 23544888
TI  - Dinuclear lanthanide(III) complexes by metal-ion-assisted hydration of di-2
      pyridyl ketone azine.
AB  - The initial employment of di-2-pyridyl ketone azine in 4f metal chemistry has led
      to a unique ligand transformation; the resulting anionic ligand is able to bridge
      two Ln(III) ions, affording neutral and cationic dinuclear complexes with
      interesting properties.

PMID- 23544889
TI  - Single surgeon experience with robot-assisted ureteroureterostomy for pathologies
      at the proximal, middle, and distal ureter in adults.
AB  - PURPOSE: To describe our initial experience with robot-assisted
      ureteroureterostomy (RUU) at the proximal, middle, and distal ureter. MATERIALS
      AND METHODS: Twelve consecutive patients underwent RUU by a single surgeon
      (D.D.E.) between July 2009 and November 2012. Indications included three
      iatrogenic injuries, two impacted stones, two ureterovaginal fistulas, two
      idiopathic ureteral strictures refractory to conservative treatment, one primary
      transitional cell carcinoma of the ureter, one colon cancer metastasis to the
      ureter, and one invasive endometriosis. There were two proximal, three middle,
      and seven distal ureteral pathologies. RESULTS: Tension-free anastomosis was
      achieved in all 12 patients. All patients with proximal and middle ureteral
      pathology received concomitant downward nephropexy (DN) as a standard part of
      RUU. Mean age of patients at the time of surgery was 52 years (range 30-69), mean
      body mass index was 30.0 kg/m(2) (range 21-38), mean operative room time was 190
      minutes (range 104-354), mean estimated blood loss was 181 mL (range 50-400), and
      mean length of excised ureter on pathologic analysis was 2.0 cm (range 1.0-4.5).
      There was one intraoperative complication in which liver and gallbladder
      laceration occurred during trocar placement. Mean length of hospital stay was 1.4
      days (range 1-5), and there were no postoperative complications. Mean follow up
      was 10 months (range 3-36). One patient had a ureteral stricture recurrence at 7
      months postoperatively that led to renal unit loss and eventual nephrectomy.
      CONCLUSION: RUU is feasible, safe, and demonstrates good outcomes for pathologies
      at the proximal, middle, and distal ureter. Concomitant DN during RUU may assist
      in achieving a tension-free anastomosis for proximal and middle ureteral repairs.

PMID- 23544891
TI  - In vitro fertilization outcomes in treated hypothyroidism.
AB  - BACKGROUND: Levothyroxine has been shown to enhance pregnancy outcomes in women
      with hypothyroidism requiring in vitro fertilization (IVF). However, the precise
      magnitude of these benefits remains to be determined. In particular, it has yet
      to be clarified whether levothyroxine may fully overcome the detrimental effects
      of hypothyroidism or, conversely, whether affected women remain at reduced
      prognosis for pregnancy outcomes. METHODS: Patients who underwent IVF
      intracytoplasmic sperm injection (ICSI) over a 3-year period were reviewed. Cases
      were deemed eligible if they were diagnosed with clinical or subclinical
      hypothyroidism and were receiving levothyroxine. Controls were two subsequently
      age-matched euthyroid women for every case. Both cases and controls were selected
      only if serum thyrotropin was <=2.5 mIU/L. RESULTS: In total, 137 women with
      treated hypothyroidism and 274 controls were included. Baseline characteristics
      of the two study groups were similar with the exception of body mass index, which
      was slightly higher among the cases (22.9+/-3.9 vs. 21.9+/-3.3 kg/m2, p=0.013).
      Most IVF-ICSI cycle outcome variables were also similar, with the exception of a
      higher rate of cancellation for poor response (3.6% vs. 0.7%, p=0.04), a longer
      duration of stimulation (10.9+/-2.2 vs. 10.1+/-2.0 days, p=0.001), a higher
      proportion of women failing to obtain viable embryos (17% vs. 7%, p=0.006), and a
      lower fertilization rate (75% vs. 86%, p=0.017) among cases. Conversely, the
      clinical pregnancy rate per started cycle, the implantation rate, and the live
      birth rate per started cycle did not differ; they were 36% and 34% (p=0.93), 28%
      and 22% (p=0.11), and 30% and 27% (p=0.50) in cases and controls, respectively.
      Subgroup analyses comparing women with (n=79) and without (n=58) thyroid
      autoimmunity and comparing women who were diagnosed with overt hypothyroidism
      (n=70) or subclinical hypothyroidism (n=67) failed to identify relevant
      differences. CONCLUSIONS: In our population, IVF-ICSI outcome was not
      significantly hampered in women with adequately treated hypothyroidism. The
      magnitude of the detected differences in cycle outcome was mild, and we failed to
      document any differences for the most relevant outcomes, i.e., pregnancy rate,
      implantation rate, and delivery rate. In conclusion, adequate levothyroxine
      treatment maintaining thyrotropin serum levels below 2.5 mIU/L may overcome the
      detrimental effects of hypothyroidism.

PMID- 23544892
TI  - Introduction: group psychotherapists as organizational consultants: diverse
      contexts, models, and approaches.

PMID- 23544890
TI  - Insulin, ascorbate, and glucose have a much greater influence than transferrin
      and selenous acid on the in vitro growth of engineered cartilage in chondrogenic
      media.
AB  - The primary goal of this study was to characterize the response of chondrocyte
      seeded agarose constructs to varying concentrations of several key nutrients in a
      chondrogenic medium, within the overall context of optimizing the key nutrients
      and the placement of nutrient channels for successful growth of cartilage tissue
      constructs large enough to be clinically relevant in the treatment of
      osteoarthritis (OA). To this end, chondrocyte-agarose constructs (o4*2.34 mm,
      30*10(6) cells/mL) were subjected to varying supplementation levels of insulin
      (0* to 30* relative to standard supplementation), transferrin (0* to 30*),
      selenous acid (0* to 10*), ascorbate (0* to 30*), and glucose (0* to 3*). The
      quality of resulting engineered tissue constructs was evaluated by their
      compressive modulus (E(-Y)), tensile modulus (E(+Y)), hydraulic permeability (k),
      and content of sulfated glycosaminoglycans (sGAG) and collagen (COL); DNA content
      was also quantified. Three control groups from two separate castings of
      constructs (1* concentrations of all medium constituents) were used. After 42
      days of culture, values in each of these controls were, respectively, E(-Y)=518+/
      78, 401+/-113, 236+/-67 kPa; E(+Y)=1420+/-430, 1140+/-490, 1240+/-280 kPa;
      k=2.3+/-0.8*10(-3), 5.4+/-7.0*10(-3), 3.3+/-1.3*10(-3) mm(4)/N.s; sGAG=7.8+/-0.3,
      6.3+/-0.4, 4.1+/-0.5%/ww; COL=1.3+/-0.2, 1.1+/-0.3, 1.4+/-0.4%/ww; and DNA=11.5+/
      2.2, 12.1+/-0.6, 5.2+/-2.8 MUg/disk. The presence of insulin and ascorbate was
      essential, but their concentrations may drop as low as 0.3* without detrimental
      effects on any of the measured properties; excessive supplementation of ascorbate
      (up to 30*) was detrimental to E(-Y), and 30* insulin was detrimental to both
      E(+Y) and E(-Y). The presence of glucose was similarly essential, and matrix
      elaboration was significantly dependent on its concentration (p<10(-6)), with
      loss of functional properties, composition, and cellularity observed at <=0.3*;
      excessive glucose supplementation (up to 3*) showed no detrimental effects. In
      contrast, transferrin and selenous acid had no influence on matrix elaboration.
      These findings suggest that adequate distributions of insulin, ascorbate, and
      glucose, but not necessarily of transferrin and selenous acid, must be ensured
      within large engineered cartilage constructs to produce a viable substitute for
      joint tissue lost due to OA.

PMID- 23544893
TI  - Cultural revelations: shining a light on organizational dynamics.
AB  - The aim of this paper is to provide a model for how elements of group relations
      and organization development perspectives can be combined in a successful
      organizational consultancy and to demonstrate through a case analysis what
      blending the two can look like in practice. The further aim of this paper is to
      provide readers-group therapists in particular-with an increased understanding of
      how to use therapeutic skills and theories in organizational consultation. The
      case study is provided to illustrate actual interventions and depict the use of
      self-as-instrument as one tool available to organizational change consultants.
      Throughout the paper, ideas are offered on how to engage organizational clients
      to work with what is irrational and unconscious as well as what is rational and
      conscious.

PMID- 23544894
TI  - Transforming medical practices: a significant opportunity for group
      psychotherapists.
AB  - Group therapists are in a unique position to be effective as change consultants
      to medical practices and hospital departments that wish to transition to
      patientcentered care (PCC) and patient- and family-centered care (PFCC). Medical
      groups are under increasing pressure to adopt PCC because it has been shown to be
      an important component of substantial improvements in health care delivery,
      including cost containment. The establishment of patient-centered care requires
      sensitive, repeated group-based interventions to be successful; group therapists
      have a deep understanding of such interventions. The paper outlines the
      literature on PCC and PFCC, considers the group processes underlying successful
      implementation, and then turns to various phases of the consulting process
      itself, including system-diagnostic interviewing, group meetings, resources, and
      tracking the consequences of the consultation.

PMID- 23544895
TI  - On the similarities of peace of mind and peace in the valley.
AB  - This article examines the practice of organization consultation using the
      adaptive leadership approach through a case example of a large system
      intervention in a peacemaking project in Nepal. The authors define core
      activities of the Adaptive Leadership model and provide parallels to
      psychodynamic group psychotherapy theory and technique that demonstrate how group
      therapists can apply their expertise to larger systems and arenas beyond the
      group therapy office.

PMID- 23544896
TI  - Applying systems-centered theory (SCT) and methods in organizational contexts:
      putting SCT to work.
AB  - Though initially applied in psychotherapy, a theory of living human systems
      (TLHS) and its systems-centered practice (SCT) offer a comprehensive conceptual
      framework replete with operational definitions and methods that is applicable in
      a wide range of contexts. This article elaborates the application of SCT in
      organizations by first summarizing systems-centered theory, its constructs and
      methods, and then using case examples to illustrate how SCT has been used in
      organizational and coaching contexts.

PMID- 23544897
TI  - The group psychotherapist consulting in organizations: toward less fear and more
      treading.

PMID- 23544898
TI  - Consulting in/to organizations/societies as traumatized living human social
      systems.

PMID- 23544899
TI  - On inveiglement.
AB  - Inveiglement is a mode of interpersonal influence and control that has particular
      relevance to group, organizational, and political life. In inveiglement, a person
      or group is diverted from knowing, believing, or thinking about an idea or a
      perception that exists mentally, or that could be generated. In the former
      situation, inveiglement may be conceived of as induced dissociation; in the
      latter, an impingement on the capacity to think and generate thoughts. In both
      situations, the individual or group becomes mentally bound by the parameters
      imposed by the other, constricting freedom to think and behave independently. I
      describe four subtypes: toxic, neurotic, communal, and presentational
      inveiglement, and provide clinical illustrations from group psychotherapy.

PMID- 23544901
TI  - Cognitive approaches to group therapy: prevention of relapse in major depressive
      and bipolar disorders.

PMID- 23544904
TI  - One day in the life of old age psychiatrists in the United Kingdom.
AB  - BACKGROUND: The provision of mental health care for older people will become
      increasingly important with rising demand related to global demographic changes.
      This project aimed to identify changes in work patterns of UK consultant old age
      psychiatrists between 1993 and 2012. METHOD: A link to an online questionnaire
      was circulated to consultant old age psychiatrists through the Faculty of Old Age
      Psychiatry, Royal College of Psychiatrists. RESULTS: In all 210 usable responses
      were received. On the survey day 71% of old age psychiatrists arrived at work
      before 9 am, and 40% left work after 6 pm. Over one-third (35%) worked for
      another hour or more at home. The range of activities was broader than previously
      reported. Administrative activity was undertaken by over 60% and acute ward work
      by only 26%. Few consultants reported time in long-stay care or day hospitals.
      Outpatient activity included Memory Clinics and Health Center Clinics. The main
      stressors reported by consultants were lack of resources and pressures from
      management-imposed, financially driven service changes. Relationships with people
      at work (including patients and their families) and outside work were the main
      identified support. CONCLUSIONS: Consultants' working hours have changed little
      since 1997, but the range and emphases of activities have changed. Changes in
      service organization are stressful and consultants are supported by relationships
      with colleagues and patients. Work patterns are changing in response to demands
      and constraints on the specialty. Research is needed into service design and work
      patterns, which can provide humane care in the current economic climate.

PMID- 23544905
TI  - Rheological study of two-dimensional very anisometric colloidal particle
      suspensions: from shear-induced orientation to viscous dissipation.
AB  - In the present study, we investigate the evolution with shear of the viscosity of
      aqueous suspensions of size-selected natural swelling clay minerals for volume
      fractions extending from isotropic liquids to weak nematic gels. Such suspensions
      are strongly shear-thinning, a feature that is systematically observed for
      suspensions of nonspherical particles and that is linked to their orientational
      properties. We then combined our rheological measurements with small-angle X-ray
      scattering experiments that, after appropriate treatment, provide the
      orientational field of the particles. Whatever the clay nature, particle size,
      and volume fraction, this orientational field was shown to depend only on a
      nondimensional Peclet number (Pe) defined for one isolated particle as the ratio
      between hydrodynamic energy and Brownian thermal energy. The measured
      orientational fields were then directly compared to those obtained for infinitely
      thin disks through a numerical computation of the Fokker-Plank equation. Even in
      cases where multiple hydrodynamic interactions dominate, qualitative agreement
      between both orientational fields is observed, especially at high Peclet number.
      We have then used an effective approach to assess the viscosity of these
      suspensions through the definition of an effective volume fraction. Using such an
      approach, we have been able to transform the relationship between viscosity and
      volume fraction (etar = f(phi)) into a relationship that links viscosity with
      both flow and volume fraction (etar = f(phi, Pe)).

PMID- 23544906
TI  - Fabrication of structured porous films by breath figures and phase separation
      processes: tuning the chemistry and morphology inside the pores using click
      chemistry.
AB  - Herein, a facile water-assisted templating technique, the so-called breath
      figures method, in combination with phase separation process, was employed to
      prepare multifunctional micropatterned films. Tetrahydrofuran solutions of
      incompatible ternary blends consisting of high-molecular-weight polystyrene, an
      amphiphilic block copolymer, polystyrene-b-poly[poly(ethylene glycol) methyl
      ether methacrylate] (PS40-b-P(PEGMA300)48), and a fluorinated homopolymer,
      poly(2,3,4,5,6-pentafluorostyrene) (P5FS21) were casted under humid atmosphere
      varying the proportion of the components. Two simultaneously occurring processes,
      i.e., the breath figures mechanism and the phase separation process, lead to
      unprecedented morphologies that could be tuned by simply varying the relative
      humidity or the composition of the blend. Confocal micro-Raman spectroscopy
      served to provide information about the location and distribution of the
      different functionalities in the films. As a result, both the amphiphilic block
      copolymer and the fluorinated polymer were mainly located in the cavities. Above
      a certain percentage of relative humidity, honeycomb structured films were
      obtained in which the block copolymer is distributed on the edge of the pore as a
      result of the affinity by the condensing water droplet and the coffee stain
      effect. The homopolymer is also preferentially situated at the pore edge, but
      forming spherical domains with narrow polydisperse sizes. Moreover, thiolated
      glucose molecules were specifically attached to the P5FS21 domains via thiol-para
      fluorine "click" reaction. Subsequently, the specific lectin (Concanavalin A,
      Canavalia ensiformis) was attached to the surface by conjugation with the glucose
      moieties. The successful binding of the Con A was demonstrated by the
      fluorescence, observed exclusively at the areas where P5FS21 domains are located.
      This nonlithographic method opens a new route to fabricate a huge variety of
      microstructured polymer films in terms of morphology not only for protein
      patterning, as illustrated in this manuscript, but also to produce a diversity of
      functional group arrangements.

PMID- 23544907
TI  - Cognitive deficits and end-of-life care among cancer patients: commentary on Gao
      et al.

PMID- 23544909
TI  - The inhibitory effects of cannabidiol on systemic malignant tumors.

PMID- 23544910
TI  - Authors' reply to Tendas et al.

PMID- 23544915
TI  - Clinical clerkship timing revisited: Support for non-uniform sequencing.
AB  - BACKGROUND: The logistical necessity of students taking required clinical
      clerkship rotations in non-uniform sequences may have significant consequences on
      performance. AIMS: To investigate (1) the impact of previous clinical clerkship
      experience and the national licensing examination (USMLE Step 1) rankings on end
      of-clerkship overall skills assessments and (2) the effect of clinical clerkship
      order on end-of-year objective structured clinical examination (OSCE)
      performance. METHOD: The core clinical phase of UCLA consists at six clinical
      clerkships during a 48-week continuum. The clerkships are structured in two
      different tracks with different rotation order. Clinical performance scores were
      analyzed for 124 year-3 students in the two different tracks. RESULTS:
      Performance, as reviewed on a standardized clinical clerkship evaluation form by
      faculty and residents, improved significantly across the clinical year,
      regardless of track suggesting an accumulated advantage of previous experiences.
      There were no significant differences between tracks on the OSCE. CONCLUSIONS:
      Overall clinical skills are more directly impacted by the time-of-year and not
      order whereas knowledge of specific specialties may be impacted by the order
      rotations that are taken. While this may not be obvious to students, perhaps we
      should share these results for their use in tracking their personal growth in
      clinical skills.

PMID- 23544916
TI  - Twelve tips for running successful junior doctor-led teaching programmes for
      medical students.
AB  - BACKGROUND: Medical students value teaching by junior doctors and find it
      comparable to consultant-led teaching. Although several junior doctor-led
      teaching programmes have been developed, there is insufficient information in the
      literature to guide junior doctors planning on developing such programmes. AIM:
      This article gives junior doctors 12 practical tips on how they might develop and
      run successful teaching programmes for medical students. RESULTS: The 12 tips are
      (1) Clearly define the scope of your programme, (2) Ensure student-defined
      learning goals are included at an early stage, (3) Inform and involve your fellow
      junior doctors in teaching, (4) Plan teaching rotas in advance, (5) Learn to
      teach effectively by attending courses, (6) Promote your programme to medical
      students as widely as possible, (7) Use varied and interactive teaching methods,
      (8) Establish rapport with students, (9) Include assessment as part of the
      teaching programme, (10) Seek feedback from attendees and senior faculty, (11)
      Establish rules for tutorials and (12) Secure formal recognition for your scheme.
      CONCLUSIONS: These 12 tips may help junior doctors to develop and manage
      successful teaching programmes. It may also be a useful guide for senior faculty
      advising junior doctors who aspire to establish such teaching programmes.

PMID- 23544917
TI  - Longitudinal assessment in an undergraduate longitudinal integrated clerkship:
      the mini Clinical Evaluation Exercise (mCEX) profile.
AB  - AIM: Student and assessor performance were examined over three academic years
      using the mini Clinical Evaluation Exercise (mCEX) as a continuous feedback tool
      across all disciplines, in all learning contexts, for an entire integrated
      undergraduate year. METHODS: Students could complete any number of mCEX, but had
      to submit a minimum number per discipline. Students were free to choose
      assessors. Assessors were not trained. Data were collected in a customised
      database, and analysed in SPSS ver 18.0.0. RESULTS: 5686 mCEX were submitted
      during 2008-2010 (Cronbach's alpha = 0.80). Marks were affected by doctor grade
      (F = 146.6, p < 0.000), difficulty of clinical encounter (F = 33.3, p < 0.000)
      and clinical discipline (F = 13.8, p < 0.000). Students most frequently sought
      harder markers (experienced general practitioner/hospital specialists). Increases
      in mCEX marks were greatest during the early, formative months (F = 42.7, p <
      0.000). More mCEX were submitted than required, without differentiation between
      weak or strong students (rxy = 0.22, p = 0.78). CONCLUSIONS: Undergraduate
      students in longitudinal clerkships acquire most skills during 'formative'
      learning. They seek 'hard' assessors, consistent with year-long mentoring
      relationships and educational/feedback value. Assessors mark consistent with a
      framework of encouraging student performance. Over an entire longitudinal
      clerkship, students complete mCEX in excess of course requirements. This study
      confirms the impact of the longitudinal context on assessor and student
      behaviour.

PMID- 23544918
TI  - Maternal protein restriction during pregnancy affects gene expression and
      immunolocalization of intestinal nutrient transporters in rats.
AB  - Intrauterine dietary restriction may cause changes in the functioning of
      offspring organs and systems later in life, an effect known as fetal programming.
      The present study evaluated mRNA abundance and immunolocalization of nutrient
      transporters as well as enterocytes proliferation in the proximal, median and
      distal segments of small intestine of rats born to protein-restricted dams.
      Pregnant rats were fed hypoproteic (6% protein) or control (17% protein) diets,
      and offspring rats were evaluated at 3 and 16 weeks of age. The presence of SGLT1
      (sodium-glucose co-transporter 1), GLUT2 (glucose transporter 2), PEPT1 (peptide
      transporter 1) and the intestinal proliferation were evaluated by
      immunohistochemical techniques and the abundance of specific mRNA for SGLT1,
      GLUT2 and PEPT1 was assessed by the real-time PCR technique. Rats born to protein
      restricted dams showed higher cell proliferation in all intestinal segments and
      higher gene expression of SGLT1 and PEPT1 in the duodenum. Moreover, in adult
      animals born to protein-restricted dams the immunoreactivity of SGLT1, GLUT2 and
      PEPT1 in the duodenum was more intense than in control rats. Taken together, the
      results indicate that changes in the small intestine observed in adulthood can be
      programmed during the gestation. In addition, they show that this response is
      caused by both up-regulation in transporter gene expression, a specific
      adaptation mechanism, and intestinal proliferation, an unspecific adaptation
      mechanism.

PMID- 23544919
TI  - Filial responsibility, perceived fairness, and psychological functioning of
      Latino youth from immigrant families.
AB  - The contributions of filial responsibility to psychological functioning were
      examined longitudinally among Latino young adolescents from immigrant families.
      Participants included 199 7th and 8th Grade Latino boys and girls (M age = 13.8)
      who were either immigrants (79%) or children of immigrants (21%). The term,
      filial responsibility, refers to children's family caregiving efforts (e.g.,
      household chores, caring for siblings). Perceived fairness, which refers to
      perceptions of equity, reciprocity, and acknowledgment, was examined as an
      important corollary describing the familial context in which youths'
      responsibilities are enacted. Over the course of this 1-year longitudinal study,
      a significant decline was observed in mean levels of caregiving, whereas a
      significant increase was observed in perceived fairness. Consistent with a
      conceptualization of filial responsibility as contributing to psychological
      development in positive and, in some contexts, negative ways, caregiving
      activities predicted increases in cooperative behavior and interpersonal self
      efficacy, whereas perceived fairness predicted declines in psychological
      distress. Implications for practitioners and policymakers working with this
      population are discussed.

PMID- 23544920
TI  - Alexithymia and marital quality: the mediating roles of loneliness and intimate
      communication.
AB  - This study examined the mediating roles of loneliness and intimate communication
      in the association between alexithymia and marital quality. Guided by a
      personality-behavioral approach to loneliness and affection exchange theory
      (AET), two actor-partner interdependence models (APIMs) were examined to test the
      associations among the variables. Path models (N = 155 couples) indicated that,
      for both spouses, loneliness and intimate communication fully mediated the
      association between alexithymia and marital quality. More specifically, higher
      alexithymia was associated with greater loneliness, which predicted lower
      intimate communication, which was related to lower marital quality. Multiple
      specific indirect effects were also significant, suggesting that the association
      between alexithymia and marital quality may be explained through divergent
      intrapersonal and interpersonal pathways. Although the magnitude of the
      intrapersonal associations was similar for both spouses, the results revealed
      gender differences in spousal interpersonal associations. For husbands,
      consistent differences were found between intrapersonal and interpersonal
      associations. Conversely, for wives, no significant differences were found
      between intrapersonal and interpersonal associations, suggesting that their
      marital quality was most strongly predicted by their own and their spouse's
      alexithymia, loneliness, and perceptions of intimate communication. Theoretical
      implications and future directions for research are also discussed.

PMID- 23544921
TI  - Ex-couples' unwanted pursuit behavior: an actor-partner interdependence model
      approach.
AB  - Unwanted pursuit behavior (UPB) refers to a wide range of repeated, unwanted, and
      privacy-violating intrusions that are inflicted to pursue an intimate or romantic
      relationship. These behaviors most often occur when partners end their romantic
      entanglements. Despite the fact that UPB is grounded in relationships,
      psychological explanations for post-breakup UPB perpetration have been restricted
      to actor effects assessed in samples of separated individuals. For that reason,
      the present study aimed to identify feasible partner effects that additionally
      explain UPB perpetration using a Flemish sample of 46 heterosexual divorced
      couples, beginning with the notion of interdependence. Using actor-partner
      interdependence models, we explored actor, partner, and gender main and
      interaction effects of anxious attachment, satisfaction, alternatives,
      investments, and conflict in the previous marriage on the perpetration of post
      divorce UPBs. The significant Partner * Gender interactions of anxious attachment
      and satisfaction, Actor * Partner interactions of anxious attachment and quality
      of alternatives, and the marginally significant partner effect of relational
      conflict underline the important role of the dyad in studying UPB perpetration.
      These findings shed new light on the nature of UPB perpetration that go beyond
      the individual and support the use of a systemic approach in clinical practices.

PMID- 23544922
TI  - Curvilinear associations between neuroticism and dyadic adjustment in treatment
      seeking couples.
AB  - Among personality traits, neuroticism has been shown to be the most significant
      predictor of dyadic adjustment. Despite some propositions arguing that low, as
      well as high levels of personality traits are maladaptive tendencies, only the
      negative linear relationship between neuroticism and couple satisfaction has been
      addressed in past research. The aim of this study was to examine the nonlinear
      association between neuroticism and dyadic adjustment for both partners of a
      clinically distressed sample of couples. The sample included 472 couples seeking
      couple therapy who completed the NEO-FFI (P. T. Costa & R. R. McCrae, 1992, NEO
      PI-R professional manual, Odessa, FL, Psychological Assessment Resources) and the
      Dyadic Adjustment Scale (G. B. Spanier, 1976, Measuring dyadic adjustment: New
      scales for assessing the quality of marriage and similar dyads, Journal of
      Marriage and the Family, 38, pp. 15-28). Results showed, for actor and partner
      effects, a significant nonlinear, inverted U-shaped relationship between
      neuroticism and dyadic adjustment. In particular, both very low levels and high
      levels of neuroticism were associated with lower dyadic adjustment for both the
      individual and his or her partner. This finding is in contrast with the
      traditional negative linear association between neuroticism and dyadic adjustment
      observed in previous research. Openness and agreeableness also positively
      predicted self and partner dyadic adjustment. Findings bear important clinical
      implications for therapists assessing and working with distressed couples.

PMID- 23544923
TI  - Attachment insecurity and infidelity in marriage: do studies of dating
      relationships really inform us about marriage?
AB  - Attachment theory provides a useful framework for predicting marital infidelity.
      However, most research has examined the association between attachment and
      infidelity in unmarried individuals, and we are aware of no research that has
      examined the role of partner attachment in predicting infidelity. In contrast to
      research showing that attachment anxiety is unrelated to infidelity among dating
      couples, 2 longitudinal studies of 207 newlywed marriages demonstrated that own
      and partner attachment anxiety interacted to predict marital infidelity, such
      that spouses were more likely to perpetrate infidelity when either they or their
      partner was high (vs. low) in attachment anxiety. Further, and also in contrast
      to research on dating couples, own attachment avoidance was unrelated to
      infidelity, whereas partner attachment avoidance was negatively associated with
      infidelity, indicating that spouses were less likely to perpetrate infidelity
      when their partner was high (vs. low) in attachment avoidance. These effects
      emerged controlling for marital satisfaction, sexual frequency, and personality;
      did not differ across husbands and wives; and did not differ across the two
      studies, with the exception that the negative association between partner
      attachment avoidance and own infidelity only emerged in 1 of the 2 studies. These
      findings offer a more complete understanding of the implications of attachment
      insecurity for marital infidelity and suggest that studies of unmarried
      individuals may not provide complete insights into the implications of various
      psychological traits and processes for marriage.

PMID- 23544924
TI  - Delinquent-oriented attitudes mediate the relation between parental inconsistent
      discipline and early adolescent behavior.
AB  - Although substantial research supports the association between parental
      inconsistent discipline and early adolescent behaviors, less is understood on
      mechanisms underlying this relation. This study examined the mediating influence
      of delinquent-oriented attitudes in early adolescence. Using a longitudinal
      sample of 324 rural adolescents and their parents, findings revealed that
      inconsistent discipline in sixth grade predicted an increase in adolescent
      delinquent-oriented attitudes by seventh grade which, in turn, predicted both an
      increase in early adolescent antisocial behaviors and a decrease in socially
      competent behaviors by eighth grade. Therefore, it appears that accepting
      attitudes toward delinquency may in part develop from experiencing inconsistent
      discipline at home and may offer a possible explanation as to why early
      adolescents later engage in more antisocial and less socially competent
      behaviors. Findings may inform family-based preventive intervention programs that
      seek to decrease behavior problems and promote social competence in early
      adolescents.

PMID- 23544925
TI  - Hazardous drinking and family functioning in National Guard veterans and spouses
      postdeployment.
AB  - The current study examined rates of alcohol misuse among National Guard (NG)
      service members and their spouses/partners, concordance of drinking behaviors
      among couples, and the effects of alcohol misuse, depression, and posttraumatic
      stress disorder (PTSD) on three measures of family functioning. This study is
      important because it addresses the topics of heavy drinking and family
      functioning in an at-risk population-NG service members returning from a combat
      zone deployment. We surveyed NG service members (1,143) and their partners (674)
      45-90 days after returning from a military deployment. Service member rates of
      hazardous drinking were 29.2% and spouses/partners 10.7%. Of the 661 linked
      couples, 26.2% were discrepant where only one member met the criteria for
      hazardous drinking and 5.4% were congruent for alcohol misuse where both members
      met hazardous drinking criteria. Service members belonging to either congruent or
      discrepant drinking groups were more distressed in their marriages/relationships
      than those in the nonhazardous group. In dyadic analyses, an unexpected partner
      effect was found for parenting outcomes; that is, when service members drink
      more, their spouses/partners are less stressed when it comes to parenting.
      Importantly, both service member and spouse/partner depression was significantly
      associated with negative family outcomes. Results from this study suggest that
      when working with these families, it is important to understand the drinking
      status of both soldier and spouse and to treat depression in addition to alcohol
      misuse.

PMID- 23544929
TI  - Amniocentesis and the risk of second trimester fetal loss in twin pregnancies:
      results from a prospective observational study.
AB  - AIM: To compare the rate of pregnancy loss between twin pregnancies undergoing a
      genetic amniocentesis (AC) and a control group with similar characteristics.
      METHODS: Prospective observational study on a population of twin pregnancies
      referred to our prenatal diagnosis unit for screening from 1990 to 2010. Those
      women referred for an AC were compared with those without indication for the
      procedure. Primary outcomes were pregnancy loss within the 4 weeks after
      procedure and pregnancy loss before 24 weeks. Secondary outcome included neonatal
      morbidity, gestational age at delivery and birth weight. results: Maternal
      characteristics were similar for both groups, except for maternal age. There was
      neither difference in the pregnancy loss rate within 4 weeks (2.7 versus 2.6%)
      nor in the loss rate before 24 weeks of gestation (1.2 versus 1.1%). Gestational
      age at birth was 36 weeks for both groups. Chorionicity and gestational age at
      procedure played no role in modifying the risk. CONCLUSION: Based on our results,
      there is no difference in the pregnancy loss rate in twin gestations, regardless
      of chorionicity or gestational age at procedure, either within 4 weeks after the
      procedure or before 24 weeks, in patients who undergo AC when compared with
      patients who do not.

PMID- 23544932
TI  - The new American Cancer Society Lung Cancer Screening guidelines and the role of
      the pathologist.

PMID- 23544933
TI  - The proposed new classification of pulmonary adenocarcinoma and the conservation
      of small tissue samples for testing.

PMID- 23544934
TI  - Graduated responsibility for pathology residents: no time for half measures.

PMID- 23544935
TI  - Ductal carcinoma in situ of the breast: current concepts and future directions.
AB  - CONTEXT: In situ carcinomas of the breast constitute 15% to 30% of all newly
      diagnosed breast cancer cases; 80% of these in situ lesions belong to the ductal
      carcinoma in situ (DCIS) category. Similar to invasive breast carcinomas, DCIS is
      not a single disease but rather many distinct diseases with different
      histopathologic and molecular characteristics, a propensity to progress to
      invasive disease, and differential response to treatment. OBJECTIVE: To review
      the classic pathologic parameters of clinical significance and the differential
      diagnosis of the DCIS lesions, present our new understanding of the importance of
      biomarkers, and discuss innovative approaches for targeted therapy in DCIS. DATA
      SOURCES: Extensive review of the relevant peer-reviewed literature. CONCLUSIONS:
      In DCIS, improved understanding of the underlying biologic pathways of tumor
      progression is expected to lead to more accurate classification and innovative
      targeted treatment approaches for the management of these lesions.

PMID- 23544936
TI  - Differential diagnosis of renal tumors with clear cytoplasm: clinical relevance
      of renal tumor subclassification in the era of targeted therapies and
      personalized medicine.
AB  - CONTEXT: The World Health Organization classification of renal tumors synthesizes
      morphologic, immunohistochemical, and molecular findings to define more than 40
      tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most
      common malignant tumor in adults and-with the exception of some rare tumors-the
      most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic
      grounds alone is generally straightforward, but challenging cases are not
      infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical
      consequences, particularly in the current era of targeted therapies. OBJECTIVE:
      To highlight morphologic mimics of clear cell renal cell carcinoma and provide
      strategies to help differentiate clear cell renal cell carcinoma from other renal
      tumors and lesions. The role of the pathologist in guiding treatment for renal
      malignancies will be emphasized to stress the importance of proper tumor
      classification in patient management. DATA SOURCES: Published literature and
      personal experience. CONCLUSIONS: In challenging cases, submission of additional
      tissue is often an inexpensive and effective way to facilitate a correct
      diagnosis. If immunohistochemical stains are to be used, it is best to use a
      panel of markers, as no one marker is specific for a given renal tumor subtype.
      Selection of limited markers, based on a specific differential diagnosis, can be
      as useful as a large panel in reaching a definitive diagnosis. For renal tumors,
      both the presence and absence of immunoreactivity and the pattern of labeling
      (membranous, cytoplasmic, diffuse, focal) are important when interpreting the
      results of immunohistochemical stains.

PMID- 23544937
TI  - Molecular profiling in non-small cell lung cancer: a step toward personalized
      medicine.
AB  - CONTEXT: Lung carcinoma is the result of sequential accumulation of genetic and
      epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse
      somatic mutations, and several of them include the so-called driver mutations,
      which may serve as "druggable" therapeutic targets. Thus, development of
      personalized approaches for the treatment of non-small cell lung carcinoma
      (NSCLC) mandates that pathologists make a precise histologic classification
      inclusive of routine molecular analysis of such tumors. OBJECTIVE: To address the
      molecular mechanisms underlying NSCLC and how this knowledge reflects the
      multidisciplinary approach in the diagnosis and management of these patients. We
      will also summarize the current available and investigational personalized
      therapies for patients with resectable early-stage, unresectable locally
      advanced, and metastatic NSCLC. DATA SOURCES: Peer-reviewed published literature
      and personal experience. CONCLUSIONS: There are multiple mechanisms involved in
      the pathogenesis of lung cancer, which operate in parallel and involve pathways
      of activation and inhibition of various cellular events. Further research is
      essential to characterize the histologic and mutational profiles of lung
      carcinomas, which will ultimately translate into improved and more personalized
      therapeutic management of patients with lung cancer.

PMID- 23544938
TI  - Central pathology review for phase III clinical trials: the enabling effect of
      virtual microscopy.
AB  - CONTEXT: Central pathology review (CPR) was initially designed as a quality
      control measure. The potential of CPR in clinical trials was recognized as early
      as in the 1960s and quickly became embedded as an integral part of many clinical
      trials since. OBJECTIVE: To review the current experience with CPR in clinical
      trials, to summarize current developments in virtual microscopy, and to discuss
      the potential advantages and disadvantages of this technology in the context of
      CPR. DATA SOURCES: A PubMed (US National Library of Medicine) search for
      published studies was conducted, and the relevant articles were reviewed,
      accompanied by the authors' experience at their practicing institution.
      CONCLUSIONS: The review of the available literature strongly suggests the growing
      importance of CPR both in the clinical trial setting as well as in second opinion
      cases. However, the currently applied approach significantly impedes efficient
      transfer of slides and patient data. Recent advances in imaging, digital
      microscopy, and Internet technologies suggest that the CPR process may be
      dramatically streamlined in the foreseeable future to allow for better diagnosis
      and quality assurance than ever before. In particular, whole slide imaging may
      play an important role in this process and result in a substantial reduction of
      the overall turnaround time required for slide review at the central location.
      Above all, this new approach may benefit the large clinical trials organized by
      oncology cooperative groups, since most of those trials involve complicated
      logistics owing to enrollment of large number of patients at several remotely
      located participating institutions.

PMID- 23544939
TI  - Recent trends in performance and current state of creatinine assays.
AB  - CONTEXT: Measured plasma or serum creatinine concentration is a primary component
      of equations used to calculate estimated glomerular filtration rate (eGFR). In
      recent years, most assay manufacturers have adopted creatinine calibration
      procedures that are traceable to the National Institute of Standards and
      Technology's Standard Reference Material 967. OBJECTIVES: To examine the current
      performance of creatinine assays, to compare changes in assay performance since
      2003, and to examine the reliability of laboratory eGFR calculations. DESIGN:
      Serum samples spiked with different concentrations of creatinine were analyzed by
      participating laboratories in the College of American Pathologists' LN24 survey.
      Participants' reported values were compared against values measured by liquid
      chromatography-isotope dilution mass spectrometry. Participants were asked to
      calculate the eGFR for certain samples, and results were compared with those
      obtained from the 4-parameter Modification of Diet in Renal Disease equation.
      RESULTS: Biases among current creatinine methods are in the range of -5% to 10%,
      compared with -7% to 34% seen in a 2003 study. This degree of bias in eGFR
      calculations is of clinical significance only for concentrations near the cut
      points used to stage chronic kidney disease. Approximately 20% of laboratories
      report eGFR values that exceed +/-1 mL/min per 1.73 m(2) from the expected eGFR
      using the 4-parameter Modification of Diet in Renal Disease equation.
      CONCLUSIONS: Since 2003, there have been improvements in the performance of
      creatinine assays, which appear to be related to the adoption of standard
      reference materials for calibration. The effect of the observed method biases in
      clinical practice now appears minimal. Laboratories should continue to monitor
      the accuracy of eGFR calculations.

PMID- 23544941
TI  - Integrity and amplification of nucleic acids from snap-frozen prostate tissues
      from robotic-assisted laparoscopic and open prostatectomies.
AB  - CONTEXT: Recently, robotic-assisted laparoscopic prostatectomy has replaced open
      retropubic radical prostatectomy as the surgical procedure of choice. This less
      invasive approach offers many advantages but exposes prostate tissue to longer
      periods of warm ischemia that may affect subsequent analysis of biomarkers.
      OBJECTIVE: To analyze the nucleic acid quality and quantity isolated from open
      versus laparoscopic prostatectomies. DESIGN: Nucleic acids were isolated from 10
      open-obtained and 10 laparoscopic-obtained tissues stored in our prostate sample
      repository. Nucleic acid integrity was assessed via electrophoresis and
      polymerase chain reaction amplification of RNA and DNA targets ranging in size
      from 125 to 939 base pairs. RESULTS: The DNA yield, integrity, and polymerase
      chain reaction amplification were identical between samples obtained from both
      surgical approaches. The RNA integrity number and yield were similar, as was beta
      2 microglobulin mRNA amplification up to 652 base pairs. However, 2 of 10 samples
      (20%) collected robotically showed decreased real-time reverse transcriptase
      polymerase chain reaction amplification of prostate-specific antigen messenger
      RNA, especially with targets larger than 300 base pairs. CONCLUSIONS: Generally,
      the quality and quantity of nucleic acids isolated from prostate tissue obtained
      via open or laparoscopic approaches are equivalent, suggesting that procurement
      of tissues is appropriate from either procedure. However, some loss of reverse
      transcriptase-polymerase chain reaction amplification of larger RNA targets was
      noted in the laparoscopic samples; appropriate design of assays to keep amplicon
      sizes small and the use of internal controls to assess RNA integrity is
      recommended.

PMID- 23544940
TI  - Diagnostic and clinical considerations in concomitant bone marrow involvement by
      plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell
      lymphocytosis: a series of 15 cases and review of literature.
AB  - CONTEXT: Plasma cell myeloma and chronic lymphocytic leukemia are both common
      hematologic malignancies, sharing many epidemiologic features. Concomitant
      detection of the 2 conditions poses special diagnostic challenges for the
      pathologist. OBJECTIVE: To describe the pathologic findings in cases of
      concomitant bone marrow involvement by myeloma and CD5(+) monoclonal B cells and
      to outline the differential diagnostic possibilities, suggest a workup for
      correct diagnosis, and examine clinical outcome. DESIGN: Fifteen cases that met
      the diagnostic criteria were identified from pathology databases at 4
      participating institutions. Morphologic findings were reviewed, additional
      immunohistochemical stains performed, and flow cytometric, cytogenetic, and
      relevant laboratory and clinical information was summarized. Previously published
      cases were searched from electronic databases and cross-references. RESULTS: Most
      patients (13 of 15) were older males. Often (11 of 15) they presented clinically
      with myeloma, yet had both monotypic plasma cells and B cells in the diagnostic
      marrow. In 4 patients, myeloma developed 24 months or later after chronic
      lymphocytic leukemia. In 7 patients, myeloma and CD5(+) B cells showed identical
      immunoglobulin light-chain restriction. Primary differential diagnoses include
      lymphoplasmacytic lymphoma, marginal zone lymphoma, and chronic lymphocytic
      leukemia with plasmacytoid differentiation. CD56 and/or cyclin D1 expression by
      plasma cells was helpful for correct diagnosis. Most patients in our cohort and
      published reports were treated for plasma cell myeloma. CONCLUSIONS: Concomitant
      detection of myeloma and chronic lymphocytic leukemia in the bone marrow is a
      rare event, which must be carefully differentiated from lymphomas with
      lymphoplasmacytic differentiation for correct treatment.

PMID- 23544942
TI  - Nonneoplastic renal cortical scarring at tumor nephrectomy predicts decline in
      kidney function.
AB  - CONTEXT: Evaluating nontumor portions of tumor nephrectomies is useful to
      diagnose nonneoplastic renal disease. OBJECTIVE: To determine the medical renal
      disease frequency and to assess the prognostic significance of the various renal
      pathologic variables with long-term follow-up in tumor nephrectomy patients.
      DESIGN: We reviewed nonneoplastic kidney sections of 456 consecutive cases from
      1998 to 2008. Seventy-five cases were excluded (19 tumor compression, 25 no
      nonneoplastic tissue, 22 embolized kidneys, 9 end stage). Special staining,
      immunofluorescence, and/or electron microscopy was performed where appropriate.
      Vascular sclerosis was scored from mild to severe; interstitial fibrosis/tubular
      atrophy and global glomerulosclerosis (GS) were expressed as percentages. Follow
      up, minimum 12 months, was evaluated in 156 cases. All renal pathologic variables
      were compared with regard to change in creatinine level from preoperative
      assessment to follow-up. RESULTS: Of 381 cases, 57 had additional medical renal
      disease (15%), most frequently diabetic nephropathy (28) and hypertensive
      nephropathy (11). Postoperative creatinine levels increased significantly in
      patients with severe arteriosclerosis or arteriolosclerosis, >5% GS, and >10%
      interstitial fibrosis/tubular atrophy. Seventy-four percent of cases with
      additional nonneoplastic diagnoses showed severe arteriolosclerosis. Higher
      corresponding GS was seen in the more affected vascular cases: mean, 5.56% GS for
      mild versus 23% GS for severe. Three patients progressed to renal failure 1 to 4
      years after nephrectomy, 2 with hypertensive nephrosclerosis and 1 with diabetic
      nephropathy. CONCLUSIONS: Medical renal disease was identified in 15% of tumor
      nephrectomy specimens. The degrees of vascular sclerosis, GS, and interstitial
      fibrosis/tubular atrophy are predictive of elevated creatinine levels in
      postnephrectomy patients. Prognostic implications of the nontumor pathology are
      important in nephrectomized patients.

PMID- 23544943
TI  - Immunocytochemistry for MUC4 and MUC16 is a useful adjunct in the diagnosis of
      pancreatic adenocarcinoma on fine-needle aspiration cytology.
AB  - CONTEXT: Diagnoses rendered as atypical/suspicious for malignancy on fine-needle
      aspiration (FNA) of pancreatic mass lesions range from 2% to 29% in various
      studies. We have identified the expression of 3 genes, MUC4, MUC16, and NGAL that
      are highly upregulated in pancreatic adenocarcinoma. In this study, we analyzed
      the expression of these markers in FNA samples to determine whether they could
      improve sensitivity and specificity. OBJECTIVE: To evaluate the utility of MUC4,
      MUC16, and NGAL in the evaluation of pancreatic FNA specimens. DESIGN: Records of
      pancreatic FNAs performed during 10 consecutive years were reviewed. Unstained
      sections from corresponding cell blocks were immunostained for MUC4, MUC16, and
      NGAL (polyclonal). Immunostaining was assessed using the H-score (range, 0-3).
      Any case with an H-score of >0.5 was considered positive. RESULTS: Cases were
      classified using cytomorphologic criteria as adenocarcinoma (31 of 64; 48.4%),
      benign (17 of 64; 26.6%), and atypical/suspicious (16 of 64; 25%). On follow-up,
      all cases (100%; 31 of 31) diagnosed as carcinoma on cytology were confirmed on
      biopsy/resection samples or by clinical follow-up (such as unresectable disease).
      Of the cases diagnosed as atypical/suspicious, 69% (11 of 16) were found to be
      positive for adenocarcinoma and 31% (5 of 16) were benign on subsequent follow
      up. Overall sensitivity and specificity, respectively, for the various markers
      for the detection of pancreatic adenocarcinoma were as follows: MUC4 (74% and
      100%), MUC16 (62.9% and 100%), and NGAL (61.3% and 58.8%). In cases that were
      atypical/suspicious on cytology, expression of MUC4 and MUC16 was 100% specific
      for carcinoma with sensitivities of 63.6% and 66.7%, respectively. CONCLUSION:
      Immunocytochemistry for MUC4 and MUC16 appears to be a useful adjunct in the
      classification of pancreatic FNA samples, especially in cases that are equivocal
      (atypical/suspicious) for adenocarcinoma on cytomorphologic assessment.

PMID- 23544944
TI  - Immunohistochemical expression of phospho-mTOR is associated with poor prognosis
      in patients with gallbladder adenocarcinoma.
AB  - CONTEXT: Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor
      prognosis and few therapeutic alternatives. The mammalian target of rapamycin
      (mTOR) is a serine/threonine kinase that plays a central role in cell growth and
      homeostasis. Its regulation is frequently altered in various tumors and is an
      attractive target for cancer therapy; however, its status in GBC remains unclear.
      OBJECTIVE: To characterize immunohistochemical expression and prognostic
      significance of phospho-mTOR in advanced gallbladder carcinoma. DESIGN: Phospho
      mTOR expression was examined by immunohistochemistry in tissue microarrays
      containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were
      divided into 2 groups according to the presence or absence of metaplasia. To
      evaluate the association of the level of phospho-mTOR expression with clinical
      variables and patient survival, the advanced GBCs were classified as having low
      or high expression. Statistical analysis was performed by using a significance
      level of P < .05, and Kaplan-Meier curves were constructed for survival analysis.
      RESULTS: Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%)
      and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with
      metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR
      immunohistochemical expression was associated with poorer prognosis in patients
      with advanced GBC (P = .02). CONCLUSIONS: Metaplasia is a common finding in
      chronic cholecystitis and is considered a precursor lesion of dysplasia. Our
      results suggest that the activation of mTOR occurs very early during the
      development of GBC, contributing to the carcinogenesis process. Phospho-mTOR
      expression is correlated with poor survival, supporting the potential of mTOR for
      targeted therapy.

PMID- 23544945
TI  - Understanding sources of bias in diagnostic accuracy studies.
AB  - CONTEXT: Accuracy is an important feature of any diagnostic test. There has been
      an increasing awareness of deficiencies in study design that can create bias in
      estimates of test accuracy. Many pathologists are unaware of these sources of
      bias. OBJECTIVE: To explain the causes and increase awareness of several common
      types of bias that result from deficiencies in the design of diagnostic accuracy
      studies. DATA SOURCES: We cite examples from the literature and provide
      calculations to illustrate the impact of study design features on estimates of
      diagnostic accuracy. In a companion article by Schmidt et al in this issue, we
      use these principles to evaluate diagnostic studies associated with a specific
      diagnostic test for risk of bias and reporting quality. CONCLUSIONS: There are
      several sources of bias that are unique to diagnostic accuracy studies. Because
      pathologists are both consumers and producers of such studies, it is important
      that they be aware of the risk of bias.

PMID- 23544946
TI  - Quality appraisal of diagnostic accuracy studies in fine-needle aspiration
      cytology: a survey of risk of bias and comparability.
AB  - CONTEXT: The quality of diagnostic accuracy studies is determined by 2 key
      factors: risk of bias and comparability. Bias can distort accuracy estimates and
      poor reporting impairs comparability. While diagnostic accuracy studies for fine
      needle aspiration cytology (FNAC) are frequently published, the methodologic
      issues associated with this body of literature have never been reviewed.
      OBJECTIVE: To assess the quality of design and reporting of diagnostic test
      accuracy studies in FNAC. DATA SOURCES: Diagnostic accuracy studies were
      identified by a Medline (US National Library of Medicine) search. Sixty-four FNAC
      diagnostic test accuracy studies were randomly selected for structured review
      with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) survey.
      Studies were divided between 2 time periods: 2000-2001 and 2009-2011.
      CONCLUSIONS: Diagnostic test accuracy studies of FNAC suffer from numerous
      deficiencies in study design, which negatively affect the reliability of accuracy
      estimates.

PMID- 23544948
TI  - Lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia.
AB  - Lymphoplasmacytic lymphoma (LPL) is a low-grade, B-cell neoplasm composed of
      small lymphocytes, plasmacytoid lymphocytes, and plasma cells that typically
      involve the bone marrow, and it is associated with an immunoglobulin M (IgM)
      gammopathy. The definition of Waldenstrom macroglobulinemia (WM) and its
      relationship to LPL has been confusing in the past. In addition, the diagnosis of
      LPL itself can be challenging because LPL lacks disease-specific morphologic,
      immunophenotypic, and genetic features to differentiate it from other mature B
      cell neoplasms. Accurate diagnosis of LPL/WM rests on recognition of the
      differential diagnostic features between LPL and other diagnostic possibilities
      and the use of the recently refined definition of WM and its relationship with
      LPL: The presence of an IgM monoclonal gammopathy of any level in the setting of
      bone marrow involvement by LPL. This review summarizes the clinical, laboratory,
      and histologic features of LPL/WM, with particular emphasis on unique aspects of
      LPL/WM that may aid in accurate diagnosis.

PMID- 23544947
TI  - Verrucous cyst with melanocytic and sebaceous differentiation: a case report and
      review of the literature.
AB  - A 58-year-old woman presented with a cystic skin lesion. Microscopic examination
      showed an intradermal cyst lined by acanthotic squamous epithelium with squamous
      eddies and compact hyperkeratosis, and changes typical of verrucous lesions.
      Mature sebaceous cells and dendritic melanocytes were present as well. To our
      knowledge, this is the first report of a verrucous cyst with areas of sebaceous
      differentiation and melanocytes. Verrucous cysts are well-known, benign lesions
      with a clear histologic pattern. Histologically, they resemble verruca vulgaris
      with acanthosis, hypergranulosis, dense keratohyaline granules, and viral
      cytopathic effects seen. Until now, melanocytes and mature sebaceous cells in the
      cyst lining have not been reported. We do not feel that these findings alter the
      expected benign nature of this lesion. Instead, we report this case to suggest
      the possible adnexal embryonic origin, given the presence of sebaceous cells and
      dendritic melanocytes that support this histologic lineage in our specific case.

PMID- 23544949
TI  - Renal oxygenation measurement during partial nephrectomy using hyperspectral
      imaging may predict acute postoperative renal function.
AB  - BACKGROUND AND PURPOSE: Digital Light Processing hyperspectral imaging (HsI)
      produces a highly sensitive, real-time tissue oxygenation map to monitor renal
      perfusion/oxygenation during partial nephrectomy (PN). Our initial experience
      with HsI revealed considerable variation in the baseline renal oxygenation, and
      we sought to correlate these differences with postoperative renal function.
      PATIENTS AND METHODS: Hyperspectral images were collected intraoperatively in
      patients undergoing PN for cortical tumors. The kidney was illuminated with
      visible light (520-645 nm), the spectrum corresponding to that of oxyhemoglobin.
      Reflectance images were captured and digitally processed to determine the
      percentage of oxyhemoglobin (HbO2) at each image pixel. Images were taken before
      hilar occlusion; these %HbO2 values were used to categorize patients as high
      (>75% HbO2) or low (<75% HbO2) oxygenation, and postoperative eGFR was assessed.
      RESULTS: There were 26 patients who underwent PN with ice cooling and HsI
      imaging. Nineteen patients had a "low" preclamp oxygenation (mean 69%) while the
      other 7 had a "high" HbO2 (mean 77%). There was no difference in tumor size,
      hematocrit value, clamp time, or preoperative eGFR between the two groups.
      Patients with a higher baseline %HbO2 had no significant postoperative change in
      their eGFR (mean 0 mL/min/1.73 m(2), +4%), while those with the lower baseline
      %HbO2 had a significant acute decline (mean 15 mL/min/1.73 m(2), -20%, P=0.02,
      0.006). CONCLUSIONS: Baseline renal oxygenation, as measured with HsI, may help
      predict risk of postoperative renal insufficiency and may distinguish between
      patients with otherwise similar baseline characteristics, such as eGFR. HsI may
      provide individualized assessment of renal function to influence intraoperative
      decision-making to help preserve renal function.

PMID- 23544950
TI  - Neuronal differentiation of embryonic stem cell derived neuronal progenitors can
      be regulated by stretchable conducting polymers.
AB  - Electrically conducting polymers are prospective candidates as active substrates
      for the development of neuroprosthetic devices. The utility of these substrates
      for promoting differentiation of embryonic stem cells paves viable routes for
      regenerative medicine. Here, we have tuned the electrical and mechanical cues
      provided to the embryonic stem cells during differentiation by precisely
      straining the conducting polymer (CP) coated, elastomeric-substrate. Upon
      straining the substrates, the neural differentiation pattern occurs in form of
      aggregates, accompanied by a gradient where substrate interface reveals a higher
      degree of differentiation. The CP domains align under linear stress along with
      the formation of local defect patterns leading to disruption of actin
      cytoskeleton of cells, and can provide a mechano-transductive basis for the
      observed changes in the differentiation. Our results demonstrate that along with
      biochemical and mechanical cues, conductivity of the polymer plays a major role
      in cellular differentiation thereby providing another control feature to modulate
      the differentiation and proliferation of stem cells. 

PMID- 23544951
TI  - Respiratory source control versus receiver protection: impact of facemask fit.
AB  - BACKGROUND: Placing a surgical mask on an infected patient (respiratory source
      control) may offer a health-care worker (HCW) more protection than donning an N95
      respirator (receiver protection). This observation was made in an in vitro study
      that used hard, nondeformable faces, and the lack of proper N95 fit may have
      accounted for the observed results. In the present study, we test the effects of
      fit on respiratory source control protection, using a soft, deformable mannequin
      head. METHODS: Resusci Anne CPR mannequin heads were placed in a chamber allowing
      6 air exchanges/hr (14 cubic feet per minute), to simulate an infected patient
      (source) and an HCW (receiver). The heads were ventilated with a tidal breathing
      pattern. The source exhaled radioactive aerosols, and a filter was attached to
      the receiver to quantify inhaled exposure. N95 respirators and surgical masks
      were tested on both heads. The degree of protection was expressed by calculating
      the reduction in exposure expressed as a simulated workplace protection factor
      (sWPF; the ratio of exposure with mask to exposure without mask) compared
      statistically using confidence intervals. RESULTS: Use of the Resusci Anne heads
      resulted in improved fit, with higher sWPF than previously reported, for example,
      for source N95 mask combinations (7,174 vs. 317) as well as receiver (7.53 vs.
      1.37). Masks placed on the receiver provided minimal exposure protection (sWPF
      range 0.99-7.53), except when sealed with Vaseline (sWPF 63.1). Any mask applied
      to the source mannequin resulted in significant reductions in exposure (sWPF
      range 214-17,038). CONCLUSION: Improved fit significantly enhanced the effects of
      source control protection. A Vaseline-sealed N95 respirator on the receiver
      offered less protection when compared with any mask on the source. Respiratory
      source control can offer more protection to HCW and potentially decrease the
      spread of aerosolized infections.

PMID- 23544952
TI  - Extemporaneous compounding in veterinary practice: a New Zealand perspective.
AB  - AIMS: The aims of this study were to explore the extent of extemporaneous
      compounding in veterinary centres throughout New Zealand and to determine whether
      pharmacists could collaborate with veterinarians to improve this service in New
      Zealand. METHODS: Questionnaires were sent to 200 randomly selected veterinarians
      in New Zealand. Semi-structured interviews were also conducted with selected
      participants from four animal facilities (zoos, research facilities and animal
      shelters) and two compounding pharmacies. RESULTS: Of the 200 veterinarian
      questionnaire recipients, 99 responded. Ten replies were withdrawn from the study
      giving a response rate of 44.5%. Of these 89, 33 (37%) compounded in their
      practice. Of the 33 compounding professionals, 3 (9%) compounded daily for
      animals under their care; 11 (34%) weekly, 18 (54%) monthly and 1 (3%) compounded
      yearly. Compounding was done by 29/33 (88%) veterinarians, 16/33 (48%) veterinary
      nurses or 6/33 (18%) others. It was carried out due to the unavailability of
      commercial products, or the need for dose adjustment to ease administration or
      improve compliance. The animals most commonly requiring veterinary compounding
      were dogs (21/33; 64%), cats (19/33; 58%) or cattle (15/33; 46%). Products which
      were commonly compounded included cyclosporin eye drops, methimazole gels and
      potassium bromide solutions. Issues commonly faced when compounding included
      unavailability of dosage forms (18/33; 55%) or appropriate ingredients (14/33;
      42%), stability (12/33; 36%), time constraints (10/33; 30%) or unavailability of
      equipment (9/33; 27%). Reasons given for not compounding included medicines being
      commercially available (38/56; 68%), pharmacy compounding for those particular
      practices (24/56; 43%), lack of training (21/56; 38%), ingredients (16/56; 29%)
      or equipment (15/56; 11%). All participants who worked with a pharmacist (11/33;
      33%) described this relationship as beneficial and indicated they would continue
      to do so in the future. CONCLUSIONS: Veterinary extemporaneous compounding exists
      in New Zealand. As pharmacists have extensive knowledge in formulating
      medications and compounding they could be of greater value to veterinarians and
      their patients. Educating both professions on the opportunities available to them
      from this collaboration could be an important step forward. CLINICAL RELEVANCE:
      This study provides new information regarding extemporaneous compounding for
      veterinary patients in New Zealand.

PMID- 23544953
TI  - A pilot Web based positive parenting intervention to help bipolar parents to
      improve perceived parenting skills and child outcomes.
AB  - BACKGROUND: Children of bipolar parents are at elevated risk for psychiatric
      disorders including bipolar disorder. Helping bipolar parents to optimize
      parenting skills may improve their children's mental health outcomes. Clear
      evidence exists for benefits of behavioural parenting programmes, including those
      for depressed mothers. However, no studies have explored web-based self-directed
      parenting interventions for bipolar parents. AIMS: The aim of this research was
      to conduct a pilot study of a web-based parenting intervention based on the
      Triple P-Positive Parenting Programme. METHOD: Thirty-nine self-diagnosed bipolar
      parents were randomly allocated to the web-based intervention or a waiting list
      control condition. Parents reported on their index child (entry criterion age 4
      10 years old). Perceived parenting behaviour and child behaviour problems
      (internalizing and externalizing) were assessed at inception and 10 weeks later
      (at course completion). Fifteen participants (4 control group and 11 intervention
      group) did not provide follow-up data. RESULTS: Levels of child behaviour
      problems (parent rated; Strengths and Difficulties Questionnaire) were above
      clinical thresholds at baseline, and problematic perceived parenting (self-rated;
      Parenting Scale) was at similar levels to those in previous studies of children
      with clinically significant emotional and behavioural problems. Parents in the
      intervention group reported improvements in child behaviour problems and
      problematic perceived parenting compared to controls. CONCLUSIONS: A web-based
      positive parenting intervention may have benefits for bipolar parents and their
      children. Initial results support improvement in child behaviour and perceived
      parenting. A more definitive study addressing the limitations of the current work
      is now called for.

PMID- 23544954
TI  - Photogeneration of reactive oxygen species on uncoated silver, gold, nickel, and
      silicon nanoparticles and their antibacterial effects.
AB  - Oxidative stress induced by reactive oxygen species (ROS) is one of the major
      toxicity mechanisms of engineered nanoparticles (NPs). To advance our knowledge
      of the photogeneration of ROS on NPs, this Letter reports the ROS generation
      kinetics of uncoated silver (AgNPs), gold (AuNPs), nickel (NiNPs), and silicon
      (SiNPs) NPs in aqueous suspension under UV irradiation (365 nm) and analyzes the
      potential ROS photogeneration mechanisms as well as the associated antibacterial
      effects. The results showed that AgNPs generated superoxide and hydroxyl
      radicals, whereas AuNPs, NiNPs, and SiNPs generated only singlet oxygen. The
      electronic structure and redox potentials of SiNPs were shown to mediate ROS
      generation. By contrast, ROS generation on AuNPs, AgNPs, and NiNPs was primarily
      due to surface plasmon resonance. The antibacterial activities of these NPs
      toward E. coli cells under UV irradiation were AgNPs (strongest) > SiNPs > NiNPs
      > AuNPs. ROS generation and metal ion release significantly enhanced the NPs'
      antibacterial activity.

PMID- 23544955
TI  - An aptamer-siRNA chimera silences the eukaryotic elongation factor 2 gene and
      induces apoptosis in cancers expressing alphavbeta3 integrin.
AB  - Small interfering RNAs (siRNAs) silence gene expression by triggering the
      sequence-specific degradation of mRNAs, but the targeted delivery of such
      reagents remains challenging and a significant obstacle to therapeutic
      applications. One promising approach is the use of RNA aptamers that bind tumor
      associated antigens to achieve the delivery of siRNAs to tumor cells displaying
      specific antigens. Wholly RNA-based constructs are advantageous because they are
      inexpensive to synthesize and their immunogenicity is low. We therefore joined an
      aptamer-recognizing alpha V and integrin beta 3 (alphavbeta3) integrin to a siRNA
      that targets eukaryotic elongation factor 2 and achieved for the first time the
      targeted delivery of a siRNA to tumor cells expressing alphavbeta3 integrin,
      causing the inhibition of cell proliferation and the induction of apoptosis
      specifically in tumor cells. The impact of our results on the development of
      therapeutic aptamer-siRNA constructs is discussed.

PMID- 23544956
TI  - Impact of soft annealing on the performance of solution-processed amorphous zinc
      tin oxide thin-film transistors.
AB  - It is demonstrated that soft annealing duration strongly affects the performance
      of solution-processed amorphous zinc tin oxide thin-film transistors. Prolonged
      soft annealing times are found to induce two important changes in the device: (i)
      a decrease in zinc tin oxide film thickness, and (ii) an increase in oxygen
      vacancy concentration. The devices prepared without soft annealing exhibited
      inferior transistor performances, in comparison to devices in which the active
      channel layer (zinc tin oxide) was subjected to soft annealing. The highest
      saturation field-effect mobility-5.6 cm(2) V(-1) s(-1) with a drain-to-source on
      off current ratio (Ion/Ioff) of 2 * 10(8)-was achieved in the case of devices
      with 10-min soft-annealed zinc tin oxide thin films as the channel layer. The
      findings of this work identify soft annealing as a critical parameter for the
      processing of chemically derived thin-film transistors, and it correlates device
      performance to the changes in material structure induced by soft annealing.

PMID- 23544957
TI  - Engineering the thermopower of C60 molecular junctions.
AB  - We report the measurement of conductance and thermopower of C60 molecular
      junctions using a scanning tunneling microscope (STM). In contrast to previous
      measurements, we use the imaging capability of the STM to determine precisely the
      number of molecules in the junction and measure thermopower and conductance
      continuously and simultaneously during formation and breaking of the molecular
      junction, achieving a complete characterization at the single-molecule level. We
      find that the thermopower of C60 dimers formed by trapping a C60 on the tip and
      contacting an isolated C60 almost doubles with respect to that of a single C60
      and is among the highest values measured to date for organic materials. Density
      functional theory calculations show that the thermopower and the figure of merit
      continue increasing with the number of C60 molecules, demonstrating the
      enhancement of thermoelectric preformance by manipulation of intermolecular
      interactions.

PMID- 23544958
TI  - Kinetics of phosphate absorption in lactating dairy cows after enteral
      administration of sodium phosphate or calcium phosphate salts.
AB  - Hypophosphataemia is frequently encountered in dairy cows during early lactation.
      Although supplementation of P is generally recommended, controversy exists over
      the suitability of oral P supplementation in animals with decreased or absent
      rumen motility. Since the effects of transruminal P absorption and the reticular
      groove reflex on the absorption kinetics of P are not well understood, it is
      unclear in how far treatment efficacy of oral P supplementation is affected by
      decreased rumen motility. Phosphate absorption was studied in six phosphate
      depleted dairy cows fitted with rumen cannulas and treated with test solutions
      containing either NaH2PO4 or CaHPO4 with acetaminophen. Each animal was treated
      orally, intraruminally and intra-abomasally in randomised order. Absorption
      kinetics of P were studied and compared with the absorption kinetics of
      acetaminophen, a marker substance only absorbed from the small intestine. Intra
      abomasal treatment with NaH2PO4 resulted in the most rapid and highest peaks in
      plasma inorganic P (Pi) concentration. Oral and intraruminal administration of
      NaH2PO4 resulted in similar increases in plasma Pi concentration from 4 to 7 h in
      both groups. Treatment with NaH2PO4 caused more pronounced peaks in plasma Pi
      concentration compared with CaHPO4. Neither transruminal P absorption nor the
      reticular groove reflex affected P absorption kinetics as determined by comparing
      plasma concentration-time curves of P and acetaminophen after administration of
      1M-phosphate salt solutions. It is concluded that oral treatment with NaH2PO4 but
      not CaHPO4 is effective in supplementing P in hypophosphataemic cows with
      adequate rumen motility. Decreased rumen motility is likely to hamper the
      efficacy of oral phosphate treatment.

PMID- 23544959
TI  - A simple approach to detect caffeine in tea beverages.
AB  - The photophysical properties of commercially available dye Acridine Orange (AO)
      describe an excellent probe for selective and sensitive detection of caffeine in
      aqueous solution. AO exists in monomer-dimer equilibrium in water. AO monomer is
      a fluorophore, but the dimer is not. Addition of caffeine to the AO leads to a
      shift in the monomer-dimer equilibrium toward the direction of AO monomer
      (fluorophore) and results in enhancement of AO fluorescence intensity.
      Enhancement of AO fluorescence intensity in the presence of caffeine has been
      treated as a signal for caffeine sensor. Furthermore, the caffeine-induced shift
      in AO monomer-dimer equilibrium is attributed to the binding of caffeine with AO
      monomer, and the binding constant was higher at a low pH range (pH ~2) compared
      to pH ~7, which results in superior caffeine sensitivity at pH ~2. Finally,
      caffeine content in commercial tea beverages has been evaluated and compared with
      the value obtained with a standard HPLC method.

PMID- 23544960
TI  - Single cell amperometry reveals glycocalyx hinders the release of
      neurotransmitters during exocytosis.
AB  - The diffusional hindrance of the glycocalyx along the cell surface on exocytotic
      peaks, observed with single cell amperometry, was investigated. Partial digestion
      of the glycocalyx with neuraminidase led to the observation of faster peaks, as
      shown by varied peak parameters. This result indicates that diffusion of small
      molecules in the partially digested glycocalyx is 2.2 faster than in the intact
      glycocalyx. Similarly, neutralization of the negative charges present in the cell
      microenvironment led to faster peak kinetics. The analysis of the vesicular
      efflux indicates that the diffusion coefficient of dopamine at the cell surface
      is at most 45% of the diffusion coefficient in free solution. This study shows
      that the glycocalyx plays an important role in the diffusion kinetics of
      processes along the cell surface, including exocytotic events. 

PMID- 23544961
TI  - Fetal magnetic resonance imaging and neurosonography in congenital neurological
      anomalies: supplementary diagnostic and postnatal prognostic value.
AB  - OBJECTIVE: To compare the diagnostic conclusions between fetal neurosonography
      and MRI in the cases of congenital neurological abnormalities, and with postnatal
      clinical and imaging evaluation, when available. METHODS: A retrospective study
      of 28 patients who underwent a fetal MRI study for suspected congenital
      neurological anomalies. The diagnoses obtained by neurosonography and MRI were
      collected and compared. Both of them were compared with the final diagnosis when
      available by necropsy or postnatal evaluation. Postnatal imaging tests were
      performed only when clinically indicated. RESULTS: The indications for the fetal
      MRI examination were: fetal ventriculomegaly, posterior fossa anomalies,
      suspected midline defects, small-for-gestational-age cephalic biometry and
      confirmed congenital CMV infection. There was a good degree of agreement beyond
      chance between both techniques (kappa test = 0.76). CONCLUSIONS: Both imaging
      modalities give a high-diagnostic performance with a good degree of agreement
      between them, when made by specialized staff. Fetal MRI is a valuable
      complementary tool to detailed neurosonography which allows an evaluation of the
      normal brain maturation from the second trimester. It also offers a higher
      diagnostic performance for some congenital abnormalities such as cortical
      development or acquired lesions.

PMID- 23544963
TI  - Severe diabetic ketoacidosis in combination with starvation and anorexia nervosa
      at onset of type 1 diabetes: a case report.
AB  - We here report a case of diabetic ketoacidosis at onset of type 1 diabetes after
      a prolonged period of starvation due to anorexia nervosa. A 53-year-old female
      with a history of anorexia nervosa was admitted to the psychiatric clinic due to
      psychotic behaviour and inability to take care of herself. Twenty-four hours
      after admission she was transferred to the clinic of internal medicine due to
      altered mental status, and laboratory screening revealed a pH of 6.895 and blood
      glucose concentration of 40 mmol/L. Due to the unusual combination of prolonged
      starvation and diabetic ketoacidosis we implemented some modifications of
      existing treatment guidelines and some special considerations regarding nutrition
      in order to prevent a re-feeding syndrome.

PMID- 23544964
TI  - Cognitive change in newly-diagnosed patients with Parkinson's disease: a 5-year
      follow-up study.
AB  - Cognitive change is frequently observed in patients with Parkinson's disease
      (PD). However, the exact profile and extent of cognitive impairments remain
      unclear due to the clinical heterogeneity of PD and methodological issues in many
      previous studies. In this study, we aimed to examine the severity, frequency, and
      profile of cognitive changes in newly diagnosed PD patients over 5 years. At
      baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59)
      and healthy controls (n = 40) were given neuropsychological tests covering six
      cognitive domains. Patients showed greater decline over time than healthy
      controls on all cognitive domains, except for attention. The profile of decline
      showed that psychomotor speed and memory were most affected. At the individual
      level 53% of the patients showed more cognitive decline than controls. Age at
      onset and memory impairment at baseline predicted cognitive decline. Cognitive
      functions in PD patients show greater decline in most domains than in healthy
      elderly over the course of 5 years. Due to selection bias as a result of
      attrition, the actual degree of decline may be greater than reported here.

PMID- 23544966
TI  - Improving asthma management: the case for mandatory inclusion of dose counters on
      all rescue bronchodilators.
AB  - BACKGROUND: Asthma remains a serious global health challenge. Poor control of
      asthma symptoms is due in part to incorrect use of oral inhaler devices that
      deliver asthma medications, such as poor inhalation technique or use of a metered
      dose inhaler (MDI) after the recommended number of doses is expelled. OBJECTIVE:
      To review published research on the potential for patients to overestimate or
      underestimate the amount of asthma rescue medication in MDIs without integrated
      dose-counting mechanisms. METHODS: We searched PubMed and EMBASE using search
      terms "dose counter and asthma" and "dose counter and metered dose inhaler" for
      English language publications up to July, 2012, with a manual search of
      references from relevant articles. RESULTS: Up to 40% of patients believe they
      are taking their asthma medication when they actually are activating an empty or
      nearly empty MDI. Device design makes it impossible for an MDI to cease
      delivering drug doses at an exact point, and the number of actuations in an MDI
      may be twice the nominal number of recommended medication doses. Once the
      recommended number of medication doses is expelled, remaining actuations deliver
      decreasing concentrations of active medication and increasing concentrations of
      propellants and excipients. This phenomenon, called "tail-off," is particularly
      problematic when medications are formulated as suspensions, as are rescue
      medications to control acute bronchospasm. Reliable inhalation of rescue
      medication could reduce asthma-related morbidity. CONCLUSION: By helping to
      ensure that patients receive accurate metered doses of asthma rescue medication
      to relieve bronchoconstriction, dose counters may help to improve asthma
      management.

PMID- 23544967
TI  - Sliding indentation enhances collagen content and depth-dependent matrix
      distribution in tissue-engineered cartilage constructs.
AB  - BACKGROUND: Current tissue-engineered cartilage constructs contain insufficient
      amounts of collagen, whose function is to resist tension. We postulate that
      dynamic tension is necessary to stimulate collagen formation. Another shortcoming
      is that tissue-engineered cartilage does not possess native zonal variations. We
      hypothesize that applying depth-varying mechanical cues would stimulate
      extracellular matrix (ECM) synthesis depth dependently. We developed a dedicated
      loading regime called sliding indentation, which enables us to apply dynamic
      tension as well as depth-varying strain fields to the chondrocyte-seeded agarose
      constructs. OBJECTIVE: In 2 study designs, we explored whether sliding
      indentation would increase collagen content and induce depth-varying ECM
      distribution. METHODS: In the first study, we developed an agarose-sandwich model
      that involves embedding of a thin chondrocyte-seeded 0.5% agarose layer between
      two cell-free 3% agarose layers. In the second study, 3-mm-thick chondrocyte
      seeded agarose constructs were created. Sliding indentation at 10% depth and 1 Hz
      was applied to constructs in both studies for 4 h/day during 28 days, and
      unloaded constructs served as control. RESULTS: Sliding indentation resulted in
      an increased amount of collagen in the produced cartilage layer. Further, sliding
      indentation for 7 days resulted in a depth-dependent response at gene expression
      levels, with the highest response in the regions that received highest strains.
      Analysis of protein expression after 28 days showed a similar depth-dependent
      distribution in all constructs, which further enhanced by sliding indentation.
      CONCLUSIONS: Sliding indentation can increase collagen content and enhances depth
      dependent ECM distribution, and is therefore a promising strategy for culturing
      cartilage with improved properties.

PMID- 23544968
TI  - Rivaroxaban for the treatment of acute coronary syndromes.
AB  - INTRODUCTION: Recurrent ischemic events after an acute coronary syndrome (ACS)
      are frequent, despite current antiplatelet therapies and revascularization.
      Warfarin reduces recurrent ischemia but increases bleeding. Warfarin is difficult
      to administer with the proportion of time achieving therapeutic international
      normalized ratios varying within and among individuals. The newer oral
      anticoagulants have predictable dose-effect relationships and no monitoring is
      required. AREAS COVERED: The pharmacology of rivaroxaban , evidence for the use
      of rivaroxaban in ACS, and the management of bleeding complications are covered
      in this article. EXPERT OPINION: Arterial thrombosis is traditionally thought to
      be more platelet mediated than clotting factor mediated. Nonetheless, in the
      acute therapy for ACS, anticoagulation is a cornerstone treatment and there is
      persistent thrombin generation. Research has focused on finding a "sweet spot" of
      anticoagulation with high anti-ischemic and low bleeding effects. It follows that
      with chronic therapy post-ACS, there could also be a "sweet-spot" of
      anticoagulation. This may depend on the intrinsic vascular disease burden, the
      intervention delivered (stenting or bypass surgery), and background antiplatelet
      therapy. Rivaroxaban, a new oral factor Xa inhibitor, in a low-dose regimen
      reduced ischemic events including mortality across a broad ACS population in the
      ATLAS-ACS trial with increased bleeding but without increasing fatal bleeding.
      Rivaroxaban is an attractive new treatment option for ACS.

PMID- 23544969
TI  - Lipid membrane domains for the selective adsorption and surface patterning of
      conjugated polyelectrolytes.
AB  - Conjugated polyelectrolytes (CPEs) are promising materials for generating
      optoelectronics devices under environmentally friendly processing conditions, but
      challenges remain to develop methods to define lateral features for improved
      junction interfaces and direct optoelectronic pathways. We describe here the
      potential to use a bottom-up approach that employs self-assembly in lipid
      membranes to form structures to template the selective adsorption of CPEs. Phase
      separation of gel phase anionic lipids and fluid phase phosphocholine lipids
      allowed the formation of negatively charged domain assemblies that selectively
      adsorb a cationic conjugated polyelectrolyte (P2). Spectroscopic studies found
      the adsorption of P2 to negatively charged membranes resulted in minimal
      structural change of the solution phase polymer but yielded an enhancement in
      fluorescence intensity (~50%) due to loss of quenching pathways. Fluorescence
      microscopy, dynamic light scattering, and AFM imaging were used to characterize
      the polymer-membrane interaction and the polymer-bound domain structures of the
      biphasic membranes. In addition to randomly formed circular gel phase domains, we
      also show that predefined features, such as straight lines, can be directed to
      form upon etched patterns on the substrate, thus providing potential routes
      toward the self-organization of optoelectronic architectures.

PMID- 23544979
TI  - [Pharmacological treatment of idiopathic overactive bladder: a literature
      review].
AB  - OBJECTIVE: To depict the recent advances in the field of pharmacological
      treatment of idiopathic overactive bladder (iOAB). METHODS: A literature search
      was conducted, using the PubMed/Medline database. Articles were included if
      published as full papers, after 2008 and before September 2012, and focused on
      recent pharmacologic treatment options for iOAB management. Publications having
      the highest level of evidence have been analyzed to summarize the available
      evidence, prioritizing the treatments available in France. RESULTS: Some meta
      analyses have been published between 2008 and 2012, gathering information about
      82 level 1 evidence studies about efficacy and safety of anticholinergics.
      According to the most recent meta-analysis, anticholinergics have proved their
      efficacy for iOAB management, reducing the number of micturitions per day by up
      to 1.59, the number of incontinence episodes per day by up to 0.7, the number of
      urgency episodes by up to 1.7, the number of urgency incontinence episodes by up
      to 2.25, and the number of nocturnal voids by up to 0.24. Safety profile was
      good, especially for solifenacin and fesoterodine, supported by strong scientific
      evidence. However, data were limited to short-term follow-up, with no
      anticholinergic drug superior to another. Few data were available about
      observance, risk factors for failure and results in specific populations.
      Anticholinergics can be used safely for management of lower urinary tract
      symptoms in men, but their role is still to be determined. Data about innovative
      drugs were still preliminary. CONCLUSIONS: Anticholinergics are a valuable option
      for management of iOAB, and have a growing role in management of lower urinary
      tract symptoms in men without bladder outlet obstruction.

PMID- 23544978
TI  - Acute stimulation of transplanted neurons improves motoneuron survival, axon
      growth, and muscle reinnervation.
AB  - Few options exist for treatment of pervasive motoneuron death after spinal cord
      injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis.
      Local transplantation of embryonic motoneurons into an axotomized peripheral
      nerve is a promising approach to arrest the atrophy of denervated muscles;
      however, muscle reinnervation is limited by poor motoneuron survival. The aim of
      the present study was to test whether acute electrical stimulation of
      transplanted embryonic neurons promotes motoneuron survival, axon growth, and
      muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to
      mimic the widespread denervation seen after disease or injury. Acutely
      dissociated rat embryonic ventral spinal cord cells were transplanted into the
      distal tibial nerve stump as a neuron source for muscle reinnervation.
      Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h.
      Other groups were used to control for the cell transplantation and stimulation.
      When neurons were stimulated acutely, there were significantly more neurons,
      including cholinergic neurons, 10 weeks after transplantation. This led to
      enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and
      more medial and lateral gastrocnemius muscles were functionally connected to the
      transplant. Reinnervation reduced muscle atrophy significantly. These data
      support the concept that electrical stimulation rescues transplanted motoneurons
      and facilitates muscle reinnervation.

PMID- 23544980
TI  - [Safety and 12-month results on stage 3-4 cystocele repair by the vaginal route
      using a light-weight mesh].
AB  - OBJECTIVE: To assess safety and efficacy at short-term of a light-weight
      polypropylene mesh (28 g/m2) for stage 3-4 cystocele repair by the vaginal route.
      MATERIAL AND METHODS: A multicentric prospective cohort study, performed between
      2010 and 2011 in seven centers. Pre-operative assessment included prolapse
      quantification using the POP-Q. Pre- and postoperative validated symptoms and
      quality of life questionnaires were used. Main objective was mesh safety.
      Secondary objectives were anatomical and functional success. RESULTS: One hundred
      and eleven patients, with a mean age of 67+/-9 years, were included in the study,
      and 94 were included in the analysis (84.7%). In 14 cases (12.8%), it was a
      secondary surgery. Two intra-operative complications occurred (2.2%). Safety
      analysis on 86 patients followed up at 12 months (91.5%) has shown satisfaction
      rate of 98.8% (85/86), mesh contraction rate of 9.3% (8/86), one case of vaginal
      mesh exposure (1.2%), no cases of pelvic pain and rate of postoperative
      dyspareunia of 5.5% (3/55). Anatomic success rate on cystocele (Ba point < -1) at
      short-term was 82/86 (95.3%) and improvement of symptoms and quality of life was
      highly significant. Five patients (5.3%) were reoperated. CONCLUSION: Cystocele
      repair by the vaginal route using a light-weight transobturator polypropylene
      mesh was safe and efficient at short-term. Long-term data are needed.

PMID- 23544981
TI  - [Translation and linguistic validation in classical Arabic of the urinary symptom
      profile (USP) questionnaire].
AB  - OBJECTIVE: The objective was to translate and linguistically validate in
      classical Arabic; the French version of the Urinary Symptom Profile (USP), the
      scale adapted to vesico-sphincter disorders. PATIENTS AND METHODS: Prospective
      study of 30 patients suffering the vesico-sphincter disorders. The translation
      was obtained by the method: translation back-translation. Patients completed the
      final questionnaire on day 0 and day 15. The feasibility, acceptability, internal
      consistency using Cronbach's alpha and test-retest repeatability by the
      interclass correlation coefficient (ICC) with the confidence interval (CI) were
      studied. RESULT: The sample consisted of 30 subjects including 20 men (66.6%) and
      10 women (33.3%). The mean age was 48+/-18, 14 years ranging from 25 to 70 years.
      The questionnaire was feasible and acceptable. The Cronbach's alpha of the three
      dimensions, urinary stress incontinence, overactive bladder and voiding
      difficulties was respectively 0.9880, 0.9774 and 0.9683, respectively; the ICC
      was 0.9762 (95% CI: 0.9307-0.9919), 0.9558 (CI 95%: 0.8738-0.9849) and 0.9385
      (95% CI: 0.8274-0.9789). CONCLUSION: The Arabic version of the classic USP had
      excellent internal consistency and excellent repeatability enable a full
      assessment of all urinary disorders and their severity.

PMID- 23544982
TI  - Urinary incontinence in women: study of surgical practice in France.
AB  - OBJECTIVE: To assess the number and the types of surgical intervention for
      urinary incontinence among women in France. We are assuming that techniques by
      suburethral sling (SUS) have replaced Burch colposuspension. MATERIAL: Using
      French hospital discharge data from the 2009 medical information system program
      (PMSI), we analyzed with regard to three relatively homogeneous diagnosis-related
      groups of patients (DRG) comprising the majority of stress urinary incontinence
      surgical interventions (cervicocystopexy, repair of the female genital apparatus,
      and hysterectomy) the detailed distribution of the different operations indexed
      in that information system. RESULTS: More than 42,000 cervicocystopexies (42,223)
      were carried out in France in 2009, and a SUS was used in 92% of the procedures
      (n=38,929). In 58% of the cases (n=24,387) this surgery was the only one, and in
      the others, it was associated with static pelvic intervention in 25% of the cases
      (n=10,741) or with a hysterectomy in 16% (n=6671). When a cervicocystopexy was
      the only operation performed, the average age of the women was 56.5 years and the
      average stay in hospital was 12.9 days. Fifty-seven percent of the
      cervicocystopexies by SUS (n=24,037) were carried out in private sector. Mean
      durations of stay were significantly shorter in the private sector than in the
      public sector for the diagnosis-related groups undergoing cervicocystopexy or
      repair of the female genital apparatus. CONCLUSION: In 2009, 10 years after its
      introduction in France, the suburethral sling is used in the overwhelming
      majority of cervicocystopexies in France. Among an estimated 4,000,000
      incontinent women in France in 2009, this surgery was undergone by approximately
      1% of them each year.

PMID- 23544983
TI  - [Urinary disorders and metabolic syndrome: prospective study].
AB  - OBJECTIVE: Metabolic syndrome (MS) risk factors are potentially implicated in the
      development of lower urinary tract symptoms (LUTS). The goals of this study were
      to analyze the prevalence of the LUTS in patients presenting with MS and to
      evaluate the correlation between the MS components and LUTS. METHODS: A
      prospective study was conducted on a group of 34 patients with MS according to
      the criteria of the NCEP ATP III. Urinary symptom profile (USP) questionnaire was
      used to evaluate LUTS. The physical examination included: weight, waist
      circumference, body mass index (BMI) and blood pressure looking for orthostatic
      hypotension. The following laboratory data were obtained: fasting blood sugar,
      postprandial glycemia, glycosylated hemoglobin (HbA1c), HDL-cholesterol, LDL
      cholesterol, triglycerides and total cholesterol. RESULTS: The mean age was 56.2
      years (+/-9.2). Twenty of the patients (58.8%) were females. All patients
      underwent diabetic and hypertension therapy. The mean BMI was 30.2+/-4.8 and
      waist circumference was 107.8+/-9.3 cm. USP total score was 8.3+/-6. Besides, 29
      (85.2%) patients had overactive bladder symptom, and 13 (38.2%) patients
      presented with urinary stress incontinence. The overactive bladder USP score was
      significantly correlated with age, waist circumference, BMI and postprandial
      glycemia. The other parameters of MS were not correlated with urinary symptoms.
      CONCLUSION: The most frequent urinary symptom in the MS was overactive bladder
      symptoms and urinary incontinence. The components of MS that influenced the USP
      score were abdominal obesity and hyperglycemia. The hypothesis of a link between
      MS and overactive bladder in diabetic patients with MS is plausible.

PMID- 23544984
TI  - [Repeat mid-urethral sling procedure for recurrent female urinary stress
      incontinence after previous mid-urethral sling].
AB  - INTRODUCTION: There are few data concerning the results of the treatment of
      recurrent stress urinary incontinence (SUI) after redo mid-urethral sling (MUS)
      procedure. METHODS: Retrospective study concerning 34 patients presenting with
      recurrent SUI following the placement of a first MUS procedure and who have
      undergone a second MUS procedure. Results were evaluated objectively (cough
      stress test) and subjectively using international consultation on incontinence
      questionnaire-short form (ICIQ-SF). RESULTS: The surgical technique for the
      placement of the first MUS was a retropubic approach in seven (20.5%) cases and a
      transobturator approach in 27 (79.5%) cases. Concerning the redo MUS procedure, a
      retropubic procedure was performed in 25 (73.5%) patients and a transobturator
      procedure in nine (26.5%) patients. Among the 34 patients, 32 (94%) were re
      examined at 2 months follow-up, and contacted through telephone after 1-year
      follow-up. Post-operatively, the cough stress test revealed no urine leakage in
      27/32 (84%) patients. Median follow-up was 15.5 months. ICIQ-SF score was 0
      (complete continence) in 19/32 (59%) patients; between 4 and 12 in 11/32 (34%)
      and between 13 and 20 in 2/32 (6%) patients. A bladder injury was diagnosed
      during the surgical procedure in two patients. A reintervention was required in
      2/34 (5%) patients because of postoperative urinary retention or bladder outlet
      obstruction. A partial sling resection was required in 2/34 (5%) patients because
      of vaginal exposure of the synthetic sling. CONCLUSION: In this study, redo MUS
      procedure was associated with good functional results despite a high rate of
      complications.

PMID- 23544985
TI  - Genital prolapse repair with Avaulta Plus mesh: functional results and quality of
      life.
AB  - PURPOSE: Evaluate anatomic and functional outcomes of genital prolapse repair by
      vaginal route using a mixed polypropylene and porcine skin mesh. PATIENTS AND
      METHODS: Prospective pilot study from January 2009 to January 2011 in the
      gynecologic department of a tertiary university hospital. Twenty patients with
      stage II-III genital prolapse underwent anterior wall prolapse repair with
      anterior Avaulta Plus mesh. Functional results were evaluated using the pelvic
      floor distress inventory-short form (PFDI-20), the pelvic floor impact
      questionnaire-7 (PFIQ-7) and the Pelvic Organ Prolapse/Urinary Incontinence
      Sexual questionnaires (PISQ-12). RESULTS: No per-operative complications
      occurred. One postoperative hematoma (5%) occurred requiring a second surgery. At
      a mean follow-up of 19.7 months, three patients had vaginal mesh exposure (15%)
      requiring a second surgery for two of them. Of the 20 women, 17 (85%) had optimal
      anatomic results and three (15%) had residual genital prolapse (Ba=-2 in two
      cases and Bp = -2 in the one). No recurrence was observed during the study
      period. A significant improvement in the PFDI-20 (P<0.001) and PFIQ-7 scores
      (P<0.001) was observed but no improvement in the PISQ-12 score. CONCLUSION: In
      this series, we reported that genital prolapse repair using Avaulta Plus mesh
      resulted in a high success rate and improved quality of life but with an
      important prevalence of vaginal mesh exposure.

PMID- 23544986
TI  - [ACT device: what place in the treatment of female urinary incontinence?].
AB  - OBJECTIVES: Assessment of the adjustable continence therapy device (ACT) in the
      treatment of female stress or mixed urinary incontinence in terms of efficacy and
      complications. MATERIAL: Between April 2005 and September 2011, the device ACT
      was put by two different operators to treat a stress and/or mixed urinary
      incontinence at women. The results were studied under two shutters: complications
      and efficacy. RESULTS: Seventy-seven women were operated. Mean age of the
      patients was of 68 years (34-87). Mean follow-up was of 22 months (1-72). Over
      the 77 patients, eight peroperative complications (10%) were noted. Twenty-five
      explantations were required in 22 patients (28%). In terms of efficacy, after an
      average follow-up of 22 months, the results were: 19 patients (25%) were
      continents, 25 (33%) very improved and five (6%) improved regards to the initial
      stage preceding the implantation. Fifteen patients (19%) were in failure. Seven
      patients (9%) were unchanged and in the course of adjustment (recent
      implantation) and six others (8%) explanted waiting for another implantation.
      CONCLUSION: The ACT procedure was feasible on a population of multi-operated
      women with 64% of improvement in our hands. Complications were rare, easily
      detected and repaired. The risk of explantation was reported to be 28%.

PMID- 23544987
TI  - Encapsulation of the herbicide picloram by using polyelectrolyte biopolymers as
      layer-by-layer materials.
AB  - Microcapsules of the herbicide picloram (PLR) were formulated by a layer-by-layer
      (LbL) self-assembly method using the polyelectrolyte biopolymers of biocompatible
      chitosan (CS) and the UV-absorbent sodium lignosulfonate (SL) as shell materials.
      The herbicide PLR was recrystallized and characterized using XRD analysis. The
      obtained PLR-loaded microcapsules were characterized by using SEM, FTIR, CLSM,
      and zeta-potential measurements. The herbicide loading and encapsulation
      efficiency were also analyzed for the PLR-loaded microcapsules. The influence of
      LbL layer numbers on herbicide release and photodegradation rates was
      investigated in vitro. The results showed that the release rates and
      photodegradation rates of PLR in microcapsules decreased with increasing number
      of CS/SL self-assembly layers. The results demonstrated that polyelectrolyte
      biopolymer-based LbL multilayer microcapsules can be a promising approach for the
      controlled release of PLR as well as other pesticides with poor photostability or
      short half-release time. 

PMID- 23544988
TI  - Chimeric RNA-DNA molecular beacons for quantification of nucleic acids, single
      nucleotide polymophisms, and nucleic acid damage.
AB  - Single nucleotide polymorphisms (SNPs) are the main cause for variations in the
      human genome. DNA lesions, such as cyclobutane pyrimidine dimers (CPDs), [6-4]
      pyrimidine-pyrimidinones, dewar pyrimidinones, and photohydrates, can
      subsequently lead to mutagenesis, carcinogenesis, and cell death. Much effort has
      focused on methods for detecting DNA, SNPs, or damaged nucleic acids. However,
      almost all of the proposed methods consist of multistep procedures, are limited
      to specific types of damage, some of these methods require expensive instruments,
      and some suffer from a high level of interferences. In this paper, we present a
      novel, simple, mix-and-read assay for the detection of nucleic acids that is
      general for all types of SNPs and nucleic acid damage. This method uses a
      chimeric RNA-DNA molecular beacon (chMB). The calibration curve of the chMB for
      detecting single base mismatch and ultraviolet (UV)-induced DNA damage shows good
      linearity (R(2) = 0.981 and 0.996, respectively) and limits of detection of 10.4
      +/- 2.2 and 8.64 +/- 1.2 nM, respectively. The chimeric RNA-DNA MB proves to be a
      more sensitive and selective tool for the quantification of nucleic acids, DNA
      mismatches, and UV-induced DNA damage than DNA MBs. 

PMID- 23544989
TI  - An expedient route to imidazo[1,4]diazepin-7-ones via a post-Ugi gold-catalyzed
      heteroannulation.
AB  - A novel diversity-oriented post-Ugi/gold(I)-catalyzed heteroannulation process
      for the synthesis of imidazo[1,4]diazepin-7-ones is elaborated. The scope and
      limitations of the protocol are discussed.

PMID- 23544990
TI  - Targeted overexpression of CKI-insensitive cyclin-dependent kinase 4 increases
      functional beta-cell number through enhanced self-replication in zebrafish.
AB  - beta-Cells of the islet of Langerhans produce insulin to maintain glucose
      homeostasis. Self-replication of beta-cells is the predominant mode of postnatal
      beta-cell production in mammals, with about 20% of rodent beta cells dividing in
      a 24-hour period. However, replicating beta-cells are rare in adults. Induction
      of self-replication of existing beta-cells is a potential treatment for diabetes.
      In zebrafish larvae, beta-cells rarely self-replicate, even under conditions that
      favor beta-cell genesis such overnutrition and beta-cell ablation. It is not
      clear why larval beta-cells are refractory to replication. In this study, we
      tested the hypothesis that insufficient activity of cyclin-dependent kinase 4 may
      be responsible for the low replication rate by ectopically expressing in beta
      cells a mutant CDK4 (CDK4(R24C)) that is insensitive to inhibition by cyclin
      dependent kinase inhibitors. Our data show that expression of CDK4(R24C) in beta
      cells enhanced beta-cell replication. CDK4(R24C) also dampened compensatory beta
      cell neogenesis in larvae and improved glucose tolerance in adult zebrafish. Our
      data indicate that CDK4 inhibition contributes to the limited beta-cell
      replication in larval zebrafish. To our knowledge, this is the first example of
      genetically induced beta-cell replication in zebrafish.

PMID- 23544991
TI  - A retrospective study of the prevalence and classification of intestinal
      neoplasia in zebrafish (Danio rerio).
AB  - For over a decade, spontaneous intestinal neoplasia has been observed in
      zebrafish (Danio rerio) submitted to the ZIRC (Zebrafish International Resource
      Center) diagnostic service. In addition, zebrafish displayed preneoplastic
      intestinal changes including hyperplasia, dysplasia, and enteritis. A total of
      195 zebrafish, representing 2% of the total fish submitted to the service, were
      diagnosed with these lesions. Neoplastic changes were classified either as
      adenocarcinoma or small cell carcinoma, with a few exceptions (carcinoma not
      otherwise specified, tubular adenoma, and tubulovillous adenoma). Tumor
      prevalence appeared similarly distributed between sexes and generally occurred in
      zebrafish greater than 1 year of age, although neoplastic changes were observed
      in fish 6 months of age. Eleven lines displayed these preneoplastic and
      neoplastic changes, including wild-types and mutants. Affected zebrafish
      originated from 18 facilities, but the majority of fish were from a single
      zebrafish research facility (hereafter referred to as the primary facility) that
      has submitted numerous samples to the ZIRC diagnostic service. Zebrafish from the
      primary facility submitted as normal sentinel fish demonstrate that these lesions
      are most often subclinical. Fish fed the diet from the primary facility and held
      at another location did not develop intestinal lesions, indicating that diet is
      not the etiologic agent.

PMID- 23544992
TI  - Evaluating the initial impact of the revised Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC) food packages on dietary intake
      and home food availability in African-American and Hispanic families.
AB  - OBJECTIVE: The present study assessed the impact of the 2009 food packages
      mandated by the Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) on dietary intake and home food availability in low-income African
      American and Hispanic parent/child dyads. DESIGN: A natural experiment was
      conducted to assess if the revised WIC food package altered dietary intake, home
      food availability, weight and various lifestyle measures immediately (6 months)
      following policy implementation. SETTING: Twelve WIC clinics in Chicago, IL, USA.
      SUBJECTS: Two hundred and seventy-three Hispanic and African-American children
      aged 2-3 years, enrolled in WIC, and their mothers. RESULTS: Six months after the
      WIC food package revisions were implemented, we observed modest changes in
      dietary intake. Fruit consumption increased among Hispanic mothers (mean = 0.33
      servings/d, P = 0.04) and low-fat dairy intake increased among Hispanic mothers
      (0.21 servings/d, P = 0.02), Hispanic children (0.34 servings/d, P < 0.001) and
      African-American children (0.24 servings/d, P = 0.02). Home food availability of
      low-fat dairy and whole grains also increased. Dietary changes, however, varied
      by racial/ethnic group. Changes in home food availability were not significantly
      correlated with changes in diet. CONCLUSIONS: The WIC food package revisions are
      one of the first efforts to modify the nutrition guidelines that govern foods
      provided in a federal food and nutrition assistance programme. It will be
      important to examine the longer-term impact of these changes on dietary intake
      and weight status.

PMID- 23544994
TI  - Evaluation of the psychometric properties of the Pediatric Parenting Stress
      Inventory (PPSI).
AB  - OBJECTIVE: This work evaluated the psychometric properties of the Pediatric
      Parenting Stress Inventory (PPSI), a new measure of problems and distress
      experienced by parents of children with chronic illnesses. METHOD: This secondary
      data analysis used baseline data from 1 sample of English-, Spanish-, and Hebrew
      speaking mothers of children recently diagnosed with cancer (n = 449) and 1
      sample of English- and Spanish-speaking mothers of children recently diagnosed
      with cancer (n = 399) who participated in 2 problem-solving skills training
      interventions. The PPSI was administered at baseline with other measures of
      maternal distress. Factor structure was evaluated using exploratory factor
      analysis (EFA) on the first sample and confirmatory factor analysis (CFA) on both
      samples. Internal consistency was evaluated using Cronbach's alpha. Construct
      validity was assessed via Spearman correlations with measures of maternal
      distress. RESULTS: EFA resulted in a stable four-factor solution with 35 items.
      CFA indicated that the four-factor solution demonstrated reasonable fit in both
      samples. Internal consistency of the subscales and full scale was adequate to
      excellent. Construct validity was supported by moderate to strong correlations
      with measures of maternal distress, depression, and posttraumatic stress
      symptoms. CONCLUSIONS: The PPSI demonstrated good psychometric properties in
      assessing current problems and distress experienced by mothers of children newly
      diagnosed with cancer. This tool may be used to identify individualized targets
      for intervention in families of children with cancer. Future studies could
      evaluate the utility and psychometrics of the PPSI with other pediatric
      populations.

PMID- 23544996
TI  - Recombinant human bone morphogenetic protein-2 stimulates the osteogenic
      potential of the Schneiderian membrane: a histometric analysis in rabbits.
AB  - This study evaluated the osteoinductive effect of the recombinant human bone
      morphogenetic protein-2 (rhBMP-2)-coated biphasic calcium phosphate (BCP) carrier
      system on the grafted sinus area, including surrounding tissues and the
      Schneiderian membrane. A total of 18 male rabbits were used in this study; two
      for in vitro and 16 for in vivo experiments. Schneiderian membranes taken from
      two animals were cultured with or without rhBMP-2, and quantitative reverse
      transcriptase-polymerase chain reaction analysis was performed. Both maxillary
      sinuses in each of the 16 animals were used to compare the in vivo effects of
      rhBMP-2-coated BCP (experimental group) and BCP alone (control group). In each
      animal, rhBMP-2-coated BCP was grafted into one of the maxillary sinuses, and the
      same amount of BCP alone was grafted into the contralateral site in random order.
      Radiologic and histometric analyses were performed at 2 and 8 weeks after
      surgery. After 2 days of culturing with or without rhBMP-2, a significant
      increase in the expression of early osteoblasts (RUNX2, type I collagen, alkaline
      phosphatase, and osteopontin) could be observed. Different histologic healing
      patterns were observed in experimental and control sites: newly formed bone
      lining the reflected sinus membrane without bone formation was observed at the
      central areas of experimental sites (window=0.06%; center=0%; membrane=20.86% of
      new bone), whereas evenly distributed new bone formation was observed at the
      control sites (window=7.27%; center=7.41%; membrane=15.58% of new bone).The
      augmented volume was well maintained at both the experimental and control sites
      during the experimental period, but at 2 weeks, the augmented volume was greater
      at the experimental sites than at the control sites (232.62 and 195.29 mm(3),
      respectively; p<0.001). These results suggest that good space maintenance in
      sinus augmentation is achieved with BCP, while the osteoinductive potential of
      the sinus membrane is activated at the early stage of healing with rhBMP-2.

PMID- 23544995
TI  - Quick to berate, slow to sleep: interpartner psychological conflict, mental
      health, and sleep.
AB  - OBJECTIVE: Relations between interpartner psychological conflict (IPC) and the
      sleep of men and women were examined, and depression and anxiety symptoms were
      assessed as intervening variables of these associations. METHOD: Participants
      were 135 cohabiting or married couples. The mean age was 36.50 (SD = 5.93) for
      women and 39.37 (SD = 7.33) for men. Most women (76%) and men (78%) were European
      American (EA) and the rest were predominantly African American (AA); there was a
      wide socioeconomic representation. Men and women reported on IPC used by their
      partner against them. Sleep was examined objectively with actigraphs, and
      multiple sleep quantity and quality measures were derived. RESULTS: Dyadic path
      analysis in which both actor and partner effects were assessed was conducted. For
      women, greater IPC by the partner was related to elevated levels of anxiety,
      which in turn was associated with shorter sleep duration and worse sleep
      efficiency; anxiety was an intervening variable. For men, IPC by the partner was
      related to greater symptoms of anxiety and depression; the latter was an
      intervening variable linking IPC with sleep quality (lower efficiency, longer
      latency). Some partner effects were observed and indicate that for both men and
      women, one's perpetration of IPC is related to increased anxiety in the partner,
      which in turn is related to longer sleep latency for the actor. CONCLUSION:
      Results build on this scant literature, and using objective well-validated
      measures of sleep highlight the importance of relationship processes and mental
      health for the sleep of men and women.

PMID- 23544997
TI  - Intramolecular oxyallyl-carbonyl (3 + 2) cycloadditions.
AB  - Cycloadditions involving oxyallyl intermediates typically require an electron
      rich diene or alkene, but we have discovered the first examples of the
      cycloaddition of heteroatom-stabilized oxyallyls onto carbonyl groups. An
      oxazolidinone-substituted oxyallyl undergoes chemoselective (3 + 2) cycloaddition
      onto the carbonyl group of a tethered dienone in preference to formation of the
      expected (4 + 3) cycloadduct. Density functional theory calculations indicated
      that the (3 + 2) cycloaddition takes place through a concerted, highly
      asynchronous mechanism. The transition state features simultaneous interactions
      of the oxyallyl LUMO with the carbonyl pi and lone-pair orbitals, making this
      reaction "hemipseudopericyclic" (halfway between purely pericyclic and purely
      pseudopericyclic). Further (3 + 2) cycloadditions involving tethered phenyl
      ketones and a tethered enone were predicted theoretically and verified
      experimentally.

PMID- 23544998
TI  - Association of TRPC1 gene polymorphisms with type 2 diabetes and diabetic
      nephropathy in Han Chinese population.
AB  - The recent genome-wide association studies reveal that chromosome 3q resides
      within the linkage region for diabetic nephropathy (DN) in type 1 and type 2
      diabetes mellitus (T1D and T2D). The TRPC1 gene is on chromosome 3q22-24, and it
      has been demonstrated that TRPC1 expression is reduced in the kidney of diabetic
      animal models. Genetic association of TRPC1 polymorphism with T1D and DN has been
      reported in European Americans. However, there are no studies reporting the
      association of TRPC1 genetic polymorphism with T2D with and without DN in Chinese
      population. This study aimed to demonstrate the genetic role of TRPC1 in the
      development of T2D with and without DN in Chinese Han population. A genetic
      association study of TRPC1 was performed in T2D cases and in nondiabetic controls
      from Han population located in Northern Chinese areas. Six tag single nucleotide
      polymorphism (SNP) markers derived from HapMap data were genotyped. Among the six
      SNPs, only rs7638459 was suspected as risk factor of T2D without DN, fitting the
      log-additive model. The adjusted odds ratio (OR) for the CC genotyping was 2.39
      (95% confidence interval (CI) = 1.00-5.68), compared with the TT genotyping. In
      addition, rs953239 was found to be a protective factor of getting DN in T2D, also
      fitting the log-additive model. When compared with the AA genotyping for SNP
      rs953239, the adjusted OR for CC genotyping was 0.63 (95% CI = 0.44-0.99). To
      summarize, this study shows that TRPC1 genetic polymorphisms are associated with
      T2D and DN in T2D in the Han Chinese population.

PMID- 23544999
TI  - ERK phosphorylation is not increased in papillary thyroid carcinomas with
      BRAF(V600E) mutation compared to that of corresponding normal thyroid tissues.
AB  - BACKGROUND: An association between a BRAF(V600E) mutation and upregulation of
      mitogen-activated protein kinase (MAPK) pathways in human papillary thyroid
      carcinoma (PTC) tissues has not been demonstrated well outside of in vitro
      studies. The aims of this study were to evaluate the activation status of
      extracellular signal-regulated kinase 1/2 (ERK1/2) in human PTCs with BRAF(V600E)
      mutations compared to that of corresponding normal thyroid tissue and to
      determine the expressions of Raf kinase inhibitor protein (RKIP) and MAPK
      phosphatase 3 (MKP-3), possible regulators of ERK1/2 activation. METHODS: We
      analyzed the presence of BRAF(V600E) mutation and the expressions of BRAF, total
      ERK, p-ERK, RKIP, and MKP-3 in 33 PTCs and corresponding normal thyroid gland
      tissues using western blot analysis. RESULTS: BRAF(V600E) mutation was found in
      28 (84.8%) of 33 PTCs, 96.4% (27/28) of which showed decreased p-ERK activity,
      while 75% (21/28) showed increased MKP-3 expression. There were significant
      differences in p-ERK and MKP-3 expressions between BRAF(V600E) (+) PTCs and
      normal thyroid glands (p < 0.001). There were no differences in expressions of
      BRAF, total ERK, and RKIP between PTCs and normal thyroid tissue, irrespective of
      the presence of BRAF(V600E) mutation. CONCLUSIONS: In human BRAF(V600E) (+) PTCs,
      ERK phosphorylation is decreased compared to normal thyroid glands and the
      observed decrease in ERK1/2 MAPK phosphorylation in BRAF(V600E) (+) PTCs may be
      associated with increased MKP-3 activity.

PMID- 23545000
TI  - Molecular mechanisms of actions of formulations of the thyroid hormone analogue,
      tetrac, on the inflammatory response.
AB  - BACKGROUND: Tetraiodothyroacetic acid (tetrac) and its nanoparticulate
      formulation (Nanotetrac) act at a cell surface receptor to block angiogenesis and
      tumor cell proliferation. OBJECTIVE: The complex anti-angiogenic properties of
      tetrac and Nanotetrac caused us to search in the literature and in certain of our
      unpublished mRNA experiments for evidence that these agents affect the early
      inflammatory response, perhaps through actions on specific cytokines and
      chemokines. RESULTS AND DISCUSSION: Tetrac and Nanotetrac inhibit expression in
      tumor cells of cytokine genes, e.g., specific interleukins, and chemokine genes,
      such as fractalkine (CX3CL1), and chemokine receptor genes (CX3CR1) that have
      been identified as high priority targets in the development of inflammation
      suppressant drugs. The possibility is also examined that tetrac formulations have
      an effect on the function of inflammatory cells.

PMID- 23545001
TI  - Characterization of focal pancreatic lesions using normalized apparent diffusion
      coefficient at 1.5-Tesla: preliminary experience.
AB  - PURPOSE: To compare the capabilities of apparent diffusion coefficient (ADC) and
      normalized ADC using the pancreatic parenchyma as reference organ in the
      characterization of focal pancreatic lesions. PATIENTS AND METHODS: Thirty-six
      patients with focal pancreatic lesions (malignant, n=18; benign tumors, n=10;
      focal pancreatitis, n=8) underwent diffusion-weighted MR imaging (DWI) at 1.5
      Tesla using 3 b values (b=0, 400, 800 s/mm(2)). Lesion ADC and normalized lesion
      ADC (defined as the ratio of lesion ADC to apparently normal adjacent pancreas)
      were compared between lesion types using nonparametric tests. RESULTS:
      Significant differences in ADC values were found between malignant (1.150 * 10(
      3)mm(2)/s) and benign tumors (2.493 * 10(-3)mm(2)/s) (P=0.004) and between benign
      tumors and mass-forming pancreatitis (1.160 * 10(-3)mm(2)/s) (P=0.0005) but not
      between malignant tumors and mass-forming pancreatitis (P=0.1092). Using
      normalized ADC, significant differences were found between malignant tumors
      (0.933 * 10(-3)mm(2)/s), benign tumors (1.807 * 10(-3)mm(2)/s) and mass-forming
      pancreatitis (0.839 * 10(-3)mm(2)/s) (P<0.0001). CONCLUSION: Our preliminary
      results suggest that normalizing ADC of focal pancreatic lesions with ADC of
      apparently normal adjacent pancreatic parenchyma provides higher degrees of
      characterization of focal pancreatic lesions than the conventional ADC does.

PMID- 23545002
TI  - Ultralow friction induced by tribochemical reactions: a novel mechanism of
      lubrication on steel surfaces.
AB  - The tribological properties of two steel surfaces rubbing against each other are
      measured while they are in contact with 1,3-diketones of varying structure. Such
      systems show after a short running-in period ultralow friction properties with a
      coefficient of friction of as low as MU = 0.005. It is suggested that the
      extremely favorable friction properties are caused by a tribochemical reaction
      between the 1,3-diketones and the steel surfaces, leading to formation of a
      chelated iron-diketo complex. The influence of temperature and the molecular
      structure of the 1,3 diketo-lubricants onto the friction properties of the system
      is elucidated under both static and dynamic conditions. With progression of the
      tribochemical reaction, the sliding surfaces become very conformal and smooth, so
      that the pressure is greatly reduced and further wear is strongly reduced. All
      iron particles potentially generated by wear during the initial running-in period
      are completely dissolved through complex formation. It is proposed that the
      tribochemical polishing reaction causes a transition from boundary lubrication to
      fluid lubrication.

PMID- 23545003
TI  - [Effects of phosphodiesterase type 5 inhibitors on lower urinary tract symptoms
      secondary to benign prostatic hyperplasia].
AB  - PURPOSE: The objective of this literature review was to report currently
      available clinical data on the effects of phosphodiesterase type 5 inhibitors
      (PDE5I) on lower urinary tract symptoms (LUTS) secondary to benign prostatic
      hyperplasia (BPH). METHODS: An international literature review was carried out in
      February 2012 from the Medline database (National Library of Medicine, United
      States). Studies on the effects of PDE5I on LUTS secondary to BPH published
      within the last 15 years (1997 to 2012) were extracted. In total, 12 studies were
      selected: four studies on sildenafil including one randomized, controlled, double
      blind study; one randomized, controlled, double-blind study on vardenafil; and
      seven studies on tadalafil including five randomized, controlled, double-blind
      studies and a 1-year open-label extension study. RESULTS: PDE5Is significantly
      improve the overall international prostatic symptom score (IPSS) compared to
      placebo. Most often, the maximum urinary flow rate (Qmax) was not significantly
      increased versus placebo. A statistically significant improvement of Qmax was
      nevertheless observed in certain studies. CONCLUSION: The available clinical data
      assessing the efficacy of PDE5 inhibition in LUTS secondary to BPH are
      convincing. PDE5Is thus are a new therapeutic class in the treatment of this
      disease and are especially interesting in patients suffering from both LUTS and
      erectile dysfunction (ED), two frequently associated diseases.

PMID- 23545004
TI  - [Lower urinary tract dysfunctions in parkinsonian syndromes: a review by the
      Neuro-Urology Comittee of the French Association of Urology].
AB  - INTRODUCTION: Lower urinary tract disorders (LUTD) are common in Parkinson's
      disease (PD) and other parkinsonian syndromes (PS). They are responsible for a
      significant morbidity and mortality and impair patients' quality of life. The
      therapeutic management of these LUTD requires to know how to distinguish the PD
      from other PS and their epidemiology and pathophysiology. OBJECTIVE: To provide a
      diagnostic and therapeutic management of LUTD in patients with PS. METHOD: A
      review of litterature using PubMed library was performed using the following
      keywords: Parkinson's disease, multiple system atrophy, lower urinary tract
      disorders, neurogenic bladder, overactive bladder, obstruction, anticholinergics,
      dopamine, prostate surgery. RESULTS: Sometimes revealing the neurological
      disease, LUTD in PS raise a diagnostic problem because they occur at an age when
      various urogynecological disorders can be intricated with neurogenic bladder
      dysfunction. The differential diagnosis between PD and multiple system atrophy is
      important to know by the urologist. The distinction is based on the semiological
      analysis, the clinical response to dopaminergic therapy and the clinical outcome
      but also on data from urodynamic explorations. The therapeutic management of
      these LUTD cannot be easy due to the difficulty of use of some pharmacological
      treatments and the risk of deterioration after inappropriate surgery. The
      different treatments include the careful use of anticholinergics, posterior
      tibial nerve stimulation, deep thalamic stimulation and low-dose intradetrusor
      injections of botulinum toxin without approval. The decision to perform prostate
      surgery will be taken with caution after proving the bladder obstruction.
      CONCLUSION: When analysing LUTD in PS, the urologist must know to question the
      initial diagnosis of PD. Treatments in order to reduce morbidity and mortality of
      these LUTD and to improve the quality of life of patients suffering from these
      degenerative diseases, will be proposed after multidisciplinary neuro-urologic
      concertation. The decision to perform prostate surgery must be taken with caution
      after proving sub-vesical obstruction.

PMID- 23545005
TI  - [Expert opinion on surgical care pathway management of neurologic patients from
      Neuro-Urology Committee of the French National Association of Urology (AFU)].
AB  - The surgical care pathway of neurologic patients has two aims: preventing urinary
      morbidity and mortality and improving their quality of life. It requires taking
      into account the specificities of disabilities in domains of body functions:
      circulatory, ventilation and digestive physiology, motor functions, sensory
      functions, mental functions, and skin fragility which are responsible of
      dependencies in this heterogeneous group of patients. This management is
      necessarily multidisciplinary to be optimal and through specific clinical care
      pathway, providing guidance to the surgical procedure: preparation of the
      surgery, its realization, and post-operative rehabilitation. The indication for
      surgery must be coordinated and validated in neuro-urology multidisciplinary
      staff. Preoperative stay in a physical and rehabilitation medicine center may be
      useful to ensure a complete assessment and anticipate problems related to
      surgery. The patient will be hospitalized in the urology department in a single
      room suited to their disabilities and handicaps. The chronic treatments should be
      not modified if possible. The lack of sensitivity does not dispense anesthesia to
      prevent autonomic hyperreflexia, the most severe complication after high complete
      spinal cord injury. The laparoscopy and sub-peritoneal surgery, the early removal
      nasogastric tube and early refeeding make it possible to early resumption of
      intestinal transit. In many cases, the patients should be transferred to a
      physical and rehabilitation medicine during post-operative period where the
      nursing care will be most suitable. A quickly adapted rehabilitation must be able
      to reduce loss of function and physical dependence.

PMID- 23545006
TI  - [The use of haemostatic agent: impact on perioperative outcomes of partial
      nephrectomy].
AB  - OBJECTIVE: To evaluate impact of the use of haemostatic agent in partial
      nephrectomy on perioperative outcomes. MATERIAL AND METHODS: We reviewed the
      files of patients candidates for partial nephrectomy in our center between 2005
      and 2010. The use of haemostatic agent and surgical procedure data were noted.
      Perioperative outcomes in haemostatic agent group were compared with
      perioperative outcomes in conventional surgical haemostasis group. RESULTS: Among
      the 131 patients included, haemostatic agent was used in 91 cases (69.5%). There
      was no statistically difference between the two groups on age, sex, BMI, ASA
      score, tumor size and RENAL score. The use of haemostatic agent was more frequent
      for patients operated with laparoscopy (10.7%, P=0.04). Concerning perioperative
      outcomes, there was no difference between the two groups on surgical
      complications, transfusions, conversion to radical nephrectomy and hospital stay.
      Median warm ischaemia time was comparable into the two groups. In multivariate
      analysis, haemorrhage, complications and transfusions were not predicted by the
      use of haemostatic agent. CONCLUSION: Use of haemostatic agent in partial
      nephrectomy had no benefice on perioperative outcomes in our series. Rapport
      between utility and cost for these agents must be discussed in partial
      nephrectomy.

PMID- 23545007
TI  - [Robotic partial nephrectomy: five years retrospective analysis at a single
      center].
AB  - INTRODUCTION: The aim of this study is to assess perioperative outcomes in a
      large series of robotic partial nephrectomy. PATIENTS AND METHODS: We performed a
      retrospective analysis of 413 patients undergoing a robotic partial nephrectomy
      in a single center between June 2006 and December 2011. We analyzed demographic
      characteristics, operative and postoperative outcomes. RESULTS: Mean age was
      58.6+/-11.9 years, body mass index was 30.5+/-7.1 kg/m2 and median ASA score 3.
      Mean tumor size was 3.2+/-1.66 cm and was divided in low, moderate and high RENAL
      nephrometry score respectively in 40%, 44% and 16%. Operative time and warm
      ischemia time were respectively 191 and 21min. Mean estimated blood loss was 200
      mL and there were 4.3% major complications (Clavien-Dindo System). Mean length of
      stay was 3.6 days. The latest estimated glomerular filtration rate (eGFR) was
      74.84 mL/min*1.73 m2 with a mean decrease of 8.6%. In multivariate analysis,
      Charlson comorbidity index (P=0.005), preoperative eGFR (P<0.001) and warm
      ischemia time (P=0.0025) were found to be independent predictors of latest
      postoperative renal function. CONCLUSION: Robotic partial nephrectomy is feasible
      and safe in experienced hands. In our study preoperative renal function, Charlson
      comorbidity index and warm ischemia time were independent predictors of latest
      eGFR.

PMID- 23545008
TI  - [Arterial anastomotic aneurysms after kidney and pancreas transplantation:
      diagnosis and management].
AB  - OBJECTIVE: The objective of our study was to assess the frequency, circumstances
      of diagnosis and treatment of anastomotic arterial aneurysms and compare them to
      the literature. MATERIAL AND METHOD: A single-center series of 3000 kidney
      transplants and 126 pancreas transplants between 1974 and 2010 was studied
      retrospectively. Ten patients had anastomotic arterial aneurysms: eight after
      kidney transplantation and two after pancreas-kidney transplantation. Diagnosis
      was based on the association Doppler ultrasonography-angioscanner. RESULTS: Ten
      arterial anastomotic aneurysms were identified. The circumstances of discovery
      were clinical in eight cases, half of them by hemodynamic collapsus. A majority
      of our patients (60%) were diagnosed in the year following the transplantation
      and two cases were discovered after transplantectomy. Pancreas-kidney
      transplantation had a high risk for arterial anastomotic aneurysm. Candida
      albicans was isolated in preoperative samples in four cases. The management
      consisted to transplantectomy in seven patients, revascularization of the lower
      limb in six patients and one renal transplant preservation. We found two lower
      limb ischemia and two deaths by a fatal intraoperative haemorrhage and vascular
      cerebral haemorrhage. No recurrence was identified after in the follow-up ranged
      from 20 months to 12 years. CONCLUSION: Arterial anastomotic aneurysm was in our
      study a serious complication that requires emergency surgery. The
      transplantectomy followed by revascularization of the limb is the treatment of
      choice associated to an appropriate antifungal or antibiotic treatment.

PMID- 23545009
TI  - [Bacillus Calmette-Guerin maintenance treatment in non-invasive bladder tumors: 1
      year follow-up results of multicenter URO-BCG-4 trial].
AB  - INTRODUCTION: Intravesical instillations of BCG remains the gold standard for
      intermediate and high risk NMIBC management. Maintenance treatment is
      recommended, however, the frequency of side effects responsible for the
      discontinuation of maintenance therapy over four out of five patients before the
      third year suggest a reduction or even spacing instillations. The objective of
      the study URO-BCG-4 was the evaluation of a new maintenance schedule by
      intravesical instillations of BCG combined reduced dose (third dose) and a
      decrease number of instillations per cycle (two or three). MATERIAL AND METHODS:
      Multicenter study of the French Association Oncologic Committee (12 university
      hospital centers), randomized, prospective, comparing reference diagram of BCG
      maintenance therapy one third of usual dose (group I) to a regimen combining
      third dose and decrease the number of instillations per cycle (two instead of
      three) (group II). We present the preliminary results at 1year of this Program of
      Clinical Research (CHU Rouen Promoter 2003-081). RESULTS: The rate of recurrence
      was respectively 9 and 7% (P=0.678) in groups I and II. The rate of tumor
      progression are 3 and 2.8% in groups I and II (P=1). Tolerance of intravesical
      instillations of BCG scored according to the WHO classification (Geneva 1979) was
      similar in the two groups. CONCLUSION: The decrease in the BCG dose (third dose)
      and the changes in the number and rate of instillations did not alter free tumor
      recurrence survival. The toxicity of intravesical instillations of BCG was
      identical in both groups. The use of the WHO classification has shown its
      limitations in the study of side effects of BCG as too complex and often not
      exhaustive. The rate of increase muscle was comparable in the two groups;
      however, a larger clinical experience is required.

PMID- 23545010
TI  - [The management of prostate cancer: a retrospective chart review in 808 French
      men undergoing biopsy].
AB  - OBJECTIVE: We explored the characteristics of a sample of men who had undergone a
      biopsy in clinical practice in France and evaluated initial treatment choice in
      men with a positive biopsy. METHODS: This was a multi-centre, retrospective chart
      review including men who had undergone a biopsy in France. Clinical variables
      were collected using an electronic data capture system. RESULTS: Eight hundred
      and eight men were included; 632 men (78%) had an initial biopsy and 176 men
      (22%) had one or more repeat biopsy. The mean age was 64 years and 9% of men were
      75 years or more. The mean (median) PSA was 11.6 (7.0) ng/mL; 25% of men had a
      PSA greater than 10 ng/mL. Twenty-eight percent of men had a suspicious DRE. A
      total of 52% of men had a positive initial and 26% a positive repeat biopsy. One
      hundred and eleven patients (34%) had low-risk PCa (stage T1c-2a, PSA<10 ng/mL,
      Gleason sum<7) and 195 (59%) were at intermediate/high risk of disease
      progression. The most common treatment was radical therapy (54% of patients),
      even in men with low-risk PCa (40% of patients). A total of 38% of low-risk
      patients chose active surveillance. CONCLUSIONS: The French biopsy sample
      appeared to be at a relatively high risk of having PCa at initial biopsy. Radical
      therapy was the most common treatment choice in men with a positive biopsy. In
      patients with low-risk PCa, radical therapy and active surveillance were used
      most often and to the same extent.

PMID- 23545011
TI  - [Economic and organizational impact of the use of a disposable sheath with a
      flexible cystoscope].
AB  - PURPOSE: To assess both economical and organizational impact as well as
      bacteriologic safety of a flexible cystoscope with sterile disposable sheath
      (FCSDS) compared to standard flexible cystoscopy (SFC) in two French urologic
      academic units. PATIENTS: Two-center prospective study, comparing the use of the
      FCSDS to the SFC on two consecutive periods of time. Two hundred and five
      patients were included and divided into each group. Duration procedures and costs
      were analysed in the two techniques. The urinary tract infection rate was also
      described. A dedicated sheaths leaks test after use was performed systematically.
      RESULTS: The preparation time of the fibroscope was longer for the sheathed
      cystoscopy group: 16.2 minutes versus 10.9 minutes for the standard group. The
      mean duration of disinfection was significantly shorter for the sheathed
      cystoscopy group: 53.8 minutes saved compared to the standard group; 99.01% of
      the tested sheaths, after their use, had no breaches. Urinary tract infections
      rate were similar in the two groups. The average cost of a sheathed cystoscopy
      compared to the standard was significantly cheaper in Lyon and almost equivalent
      in Marseille. CONCLUSION: The FCSDS allows significant saving over the
      disinfection duration, consumable costs and staff costs, while ensuring patient
      bacteriologic safety similar to SFC.

PMID- 23545012
TI  - [Vascular complication of an acute pyelonephritis].
AB  - This article reports a rare case of acute pyelonephritis with bacteriemia due to
      non-tiphoidal Salmonella associated with a mycotic aneurysm. The patient was a 75
      year-old woman without histories of immunosuppression or urologic deformation. It
      was about a patient presenting a feverish access and urinary symptoms. Blood
      culture and urine culture showed Salmonella enteritidis; in spite of a prolonged
      antibiotic treatment, the multiple bacteriological explorations remained
      positive. The research for this infection source allowed the discovery of a
      thoracic aorta aneurysm with hypermetabolism in the PET-scan carrying the
      diagnosis of mycotic aneurysm. Urinary salmonellosis represents 0.07% (Tena et
      al., 2007 [1]) of the urinary tract infections. They are rarely found in healthy
      patients; their eradication can turn out to be difficult when the infection
      source persists.

PMID- 23545013
TI  - Methodology for setup and data processing of mobile air quality measurements to
      assess the spatial variability of concentrations in urban environments.
AB  - A case study is presented to illustrate a methodology for mobile monitoring in
      urban environments. A dataset of UFP, PM2.5 and BC concentrations was collected.
      We showed that repeated mobile measurements could give insight in spatial
      variability of pollutants at different micro-environments in a city. Streets of
      contrasting traffic intensity showed increased concentrations by a factor 2-3 for
      UFP and BC and by <10% for PM2.5. The first quartile (P25) of the mobile
      measurements at an urban background zone seems to be good estimate of the urban
      background concentration. The local component of the pollutant concentrations was
      determined by background correction. The use of background correction reduced the
      number of runs needed to obtain representative results. The results presented,
      are a first attempt to establish a methodology for setup and data processing of
      mobile air quality measurements to assess the spatial variability of
      concentrations in urban environments. 

PMID- 23545014
TI  - The physical impacts of microplastics on marine organisms: a review.
AB  - Plastic debris at the micro-, and potentially also the nano-scale, are widespread
      in the environment. Microplastics have accumulated in oceans and sediments
      worldwide in recent years, with maximum concentrations reaching 100 000 particles
      m(3). Due to their small size, microplastics may be ingested by low trophic
      fauna, with uncertain consequences for the health of the organism. This review
      focuses on marine invertebrates and their susceptibility to the physical impacts
      of microplastic uptake. Some of the main points discussed are (1) an evaluation
      of the factors contributing to the bioavailability of microplastics including
      size and density; (2) an assessment of the relative susceptibility of different
      feeding guilds; (3) an overview of the factors most likely to influence the
      physical impacts of microplastics such as accumulation and translocation; and (4)
      the trophic transfer of microplastics. These findings are important in guiding
      future marine litter research and management strategies.

PMID- 23545015
TI  - Synthesis and degradation of backbone photodegradable polyester dendrimers.
AB  - Dendrimers with fully photodegradable backbones were synthesized through the
      incorporation of photodegradable o-nitrobenzyl esters into a new dendrimer
      monomer based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA). Dendrons were
      synthesized using a divergent approach, and were subsequently coupled to a core
      molecule in the final step. Photodegradation was performed and it was
      demonstrated that the molecules degrade to release bis-MPA. The accessibility of
      these molecules opens new avenues for the preparation of well-defined, fully
      photodegradable materials.

PMID- 23545017
TI  - Riding the waves of change.

PMID- 23545018
TI  - Early success for Australia's bowel screening program: let's move it along.

PMID- 23545016
TI  - Antiangiogenesis effects of endostatin in retinal neovascularization.
AB  - PURPOSE: Pathological retinal angiogenesis is a major cause of vision loss.
      Endostatin is a natural antiangiogenesis antitumor protein that is widely used in
      cancer studies. In this study, we investigated the efficacy and potential
      mechanisms of endostatin for the prevention of retinal neovascularization both in
      vitro and in vivo. METHODS: Human umbilical vein endothelial cells (HUVECs) were
      used for the in vitro studies. HUVECs were incubated with endostatin or the
      vascular endothelial growth factor (VEGF) and endostatin for different time
      points. Cell proliferation, migration, cell cycling, and tube formation studies
      were carried out using a Cell Counting Kit-8 assay, a Transwell assay, flow
      cytometry, and a Matrigel assay, respectively. Enzyme-Linked Immunosorbent Assay
      (ELISA) was used to study VEGF and pigment epithelial-derived factor (PEDF)
      protein secretion from the HUVECs at different time points. A murine oxygen
      induced retinopathy (OIR) model was used for the in vivo studies. Seven-day-old
      C57BL/6J pups (p7) were exposed to 75% oxygen for 5 days. On p12, the animals
      were returned to a normal atmosphere and were immediately injected
      intravitreously with 1.5 MUL of a 5 mg/mL endostatin solution. At p18, the mice
      were perfused with fluorescein-dextran-FITC, and their retinas were flat mounted
      to measure the nonperfused area. Retinal VEGF and PEDF levels were also measured
      by ELISA Kits in the OIR mice at p18. RESULTS: In vitro, endostatin inhibited
      HUVEC proliferation in a dose-dependent manner and also inhibited HUVEC
      proliferation in a VEGF-containing medium. Additionally, endostatin can inhibit
      migration, tube formation, and VEGF secretion in HUVECs, while also inducing
      apoptosis in HUVECs at several time points. These effects were statistically
      significant when compared to the control group (P<0.05). In vivo, a single
      intravitreous injection of endostatin reduced the retinal nonperfused area from
      30% in the control group to 23% in the treatment group (P<0.0001). Intravitrous
      injection of endostatin reduced VEGF levels in retinas, while it increased PEDF
      levels. CONCLUSIONS: Endostatin showed convincing inhibitory effects on
      angiogenesis both in vitro and in vivo. The inhibitory effects may be, at least
      partly, resulted from the restoration of the PEDF/VEGF ratio. These data suggest
      that endostatin could offer an innovative pharmaceutical strategy for the
      prevention of retinal neovascularization.

PMID- 23545019
TI  - Improving coordination of care between specialist and general practice for people
      with chronic pain.

PMID- 23545020
TI  - Is autism one or multiple disorders?

PMID- 23545021
TI  - Should Australian medical students deliver babies?

PMID- 23545022
TI  - Should hospitals have intensivist consultants in-house 24 hours a 01? - Yes.

PMID- 23545023
TI  - Should hospitals have intensivist consultants in-house 24 hours a 01? - No.

PMID- 23545024
TI  - Comparative effectiveness research - the missing link in evidence-informed
      clinical medicine and health care policy making.

PMID- 23545025
TI  - Improving flu prevention posters and reducing the risk of infection during
      outbreaks.

PMID- 23545026
TI  - The need for quality and quantity in emergency medical care rotations for
      interns.

PMID- 23545027
TI  - An audit of dabigatran etexilate prescribing in Victoria.

PMID- 23545028
TI  - The quality of international normalised ratio control in southern Tasmania.

PMID- 23545029
TI  - Global health training and postgraduate medical education in Australia: the case
      for greater integration.
AB  - Global health (GH) training is well established overseas (particularly in North
      America) and reflects an increasing focus on social accountability in medical
      education. Despite significant interest among trainees, GH is poorly integrated
      with specialty training programs in Australia. While there are numerous benefits
      from international rotations in resource-poor settings, there are also risks to
      the host community, trainee and training provider. Safe and effective placements
      rely on firm ethical foundations as well as strong and durable partnerships
      between Australian and overseas health services, educational institutions and GH
      agencies. More formal systems of GH training in Australia have the potential to
      produce fellows with the skills and knowledge necessary to engage in regional
      health challenges in a global context.

PMID- 23545030
TI  - Risk of measles transmission on aeroplanes: Australian experience 2007-2011.
AB  - OBJECTIVE: To quantify the risk of transmission of measles associated with
      infectious people who travelled on aeroplane flights to or within Australia.
      DESIGN, SETTING AND SUBJECTS: Data were obtained from state and territory health
      authorities on all measles notifications from January 2007 to June 2011 for
      people who were likely to have been infectious or infected while travelling on
      aeroplanes in Australia. RESULTS: Forty-five infectious people travelled on
      aeroplanes. Twenty secondary infections occurred in people on seven of 49 flights
      (14%; 95% CI, 6%-29%), comprising 19% (95% CI, 8%-40%) of the 36 international
      flights and none of 13 (95% CI, 0-28%) domestic flights that carried infectious
      people. Secondary infections occurred in nine people who were seated within two
      rows of the index case and in 11 people who were seated outside of two rows.
      Secondary transmission was more likely to occur with younger index cases (P =
      0.025) and when there were multiple infectious people travelling (P = 0.018).
      About a third(15/49) of flight manifests were available to health authorities
      within 5 days oftravel. CONCLUSION: Despite secondary measles transmission
      occurring on 19% of international flights carrying infectious people, risk was
      not clearly related to seating proximity, and contact tracing was ineffective,
      especially given delays in diagnosis, notification and accessing flight
      manifests. We recommend that direct contact tracing to identify susceptible
      people exposed to people infected with measles on aeroplane flights should not be
      undertaken routinely, and other strategies should be considered.

PMID- 23545031
TI  - International medical electives undertaken by Australian medical students:
      current trends and future directions.
AB  - OBJECTIVES: To estimate the proportion of students in Australian medical schools
      who undertake international medical electives (IMEs), particularly in developing
      countries, and to ascertain which medical schools provide predeparture training
      and postelective debriefing. DESIGN, SETTING AND PARTICIPANTS: Extraction of data
      on the number of students undertaking electives from the Medical Schools Outcomes
      Database (MSOD) for the 2013s 2006 to 2010; and interviews with the directors of
      each medical school in Australia in May to July 2012 to ascertain the
      availability of predeparture training and postelective debriefing. MAIN OUTCOME
      MEASURES: The proportion of medical students undertaking IMEs overall and within
      developing countries and the proportion of medical schools with optional and
      mandatory predeparture training and postelective debriefing. RESULTS: Fifty-three
      per cent of graduate-entry (GE) program students and 35% of high-school entry
      (HSE) program students undertook IMEs. Fifty-nine per cent of electives
      undertaken by GE program students were in developing countries, compared with 56%
      for HSE program students. Predeparture training was offered by 12 of the 16
      Australian medical schools, but it was mandatory in only six. Only eight schools
      offer postelective debriefing. CONCLUSIONS: A large proportion of Australian
      medical students undertake IMEs in developing countries. However, a considerable
      proportion of students do not undertake formal preparation for, or reflection on,
      their experiences. Predeparture training and postelective debriefing should be
      scaled up across Australian medical schools to provide students with the guidance
      and support to maximise the benefits and minimise risks associated with
      undertaking IMEs in developing countries.

PMID- 23545032
TI  - Shift to earlier stage at diagnosis as a consequence of the National Bowel Cancer
      Screening Program.
AB  - OBJECTIVE: To assess the impact of the National Bowel Cancer Screening Program
      (NBCSP) in South Australia. DESIGN, SETTING AND PARTICIPANTS: A cohort comparison
      of colorectal cancer (CRC) patient data from the NBCSP register and the South
      Australian Cancer Registry. Patient records of those invited to take part in
      screening through the NBCSP, those who participated in the program, and those
      with positive test results were compared with those of the rest of the study
      population (excluding the group of interest) on an intention-to-screen basis.
      MAIN OUTCOME MEASURE: Stage of CRC at diagnosis as a surrogate marker for effect
      on CRC mortality. RESULTS: Of 3481 eligible patients, 221 had been invited to the
      NBCSP. Invitees were more likely to have stage A lesions compared with all other
      patients (34.8% versus 19.2%; P < 0.001), and half as likely to have stage D CRC
      (5.4% versus 12.4%; P < 0.001). A further shift towards earlier stage was seen in
      those who participated in screening and those with positive test results compared
      with all other patients (38.8% stage A and 3.0% stage D in screening participants
      versus 19.3% stage A and 12.4% stage D in all other patients; and 39.7% stage A
      and 2.6% stage D in those with positive test results versus 19.3% stage A and
      12.4% stage D in all other patients; P < 0.001). CONCLUSIONS: CRCs were diagnosed
      at a significantly earlier stage in people invited to the NBCSP compared with
      those who were not invited, regardless of participation status or test result.
      The NBCSP should lead to reductions in CRC mortality in Australia.

PMID- 23545033
TI  - Visceral leishmaniasis in a patient taking adalimumab for rheumatoid arthritis.

PMID- 23545034
TI  - Emerging inequality and potential unconstitutionality - the case for reform of
      the intern priority system.
AB  - Internship selection is becoming more competitive due to substantial increases in
      numbers of medical graduates. Australian states operate a "priority system" for
      medical internship selection which discriminates against Australian interstate
      applicants. This discrimination arguably infringes section 117 of the Australian
      Constitution, which seeks to ensure that all citizens are treated equally and
      promotes national unity. The priority system should be reformed. It is
      inequitable and inconsistent with other aspects of medical training and
      regulation.

PMID- 23545035
TI  - Dr Burnt's consultation. A day in the life of an oncology registrar.

PMID- 23545040
TI  - Analysis of influence of voltage on potential barrier on BiCuVOX and BiTiVOX
      ceramics.
AB  - The BiMeVOx family of compounds appears to be more attractive for applications at
      low temperatures when ionic conductivity is the determining parameter. The
      objective of this study was to analysis the influence of voltage of the behavior
      of the Schottky barrier in both BiCuVOX and BiTiVOX. The samples were analyzed by
      atomic force microscopy and electric force microscopy (EFM). EFM experiments were
      conducted to map the electric field distribution on the surface. The formation of
      Schottky barriers was observed, and their height and width measured. BiCuVOX
      samples show a barrier width of 140 nm, and BiTiVOX shows a barrier width of 350
      nm. The applied voltage has no effect on the barrier width but increases the peak
      height as observed in the cantilever frequency as measured with the EFM
      technique.

PMID- 23545041
TI  - Annihilation of the acromion: a rare case of primary scapular lymphoma.

PMID- 23545043
TI  - Advances in immune regulation in transplantation.
AB  - In the last three decades, we have observed a substantial progress in the organ
      and cell transplantation. New immune suppressive agents including calcineurin
      blockers and mTOR inhibitors improved transplantation outcome, but two key
      problems -- rejection of transplanted organs and graft versus host disease (GVHD)
      -- continue to be main obstacles after transplantation. Immune response is
      regulated with coordination of a varying number of cells. T regulatory cells
      orchestrate other cell responses and eventually limit immune activation and
      induce immune tolerance. Stimulation of negative costimulatory molecules and
      adoptive transfer of immunosuppressive cells including regulatory cells are
      promising therapies that would improve outcome of patients with organ or cell
      transplantation.

PMID- 23545042
TI  - Novel therapeutic approaches for Leber's hereditary optic neuropathy.
AB  - Many human childhood mitochondrial disorders result from abnormal mitochondrial
      DNA (mtDNA) and altered bioenergetics. These abnormalities span most of the
      mtDNA, demonstrating that there are no "unique" positions on the mitochondrial
      genome that when deleted or mutated produce a disease phenotype. This diversity
      implies that the relationship between mitochondrial genotype and clinical
      phenotype is very complex. The origins of clinical phenotypes are thus unclear,
      fundamentally difficult-to-treat, and are usually clinically devastating. Current
      treatment is largely supportive and the disorders progress relentlessly causing
      significant morbidity and mortality. Vitamin supplements and pharmacological
      agents have been used in isolated cases and clinical trials, but the efficacy of
      these interventions is unclear. In spite of recent advances in the understanding
      of the pathogenesis of mitochondrial diseases, a cure remains elusive. An optimal
      cure would be gene therapy, which involves introducing the missing gene(s) into
      the mitochondria to complement the defect. Our recent research results indicate
      the feasibility of an innovative protein-transduction ("protofection")
      technology, consisting of a recombinant mitochondrial transcription factor A
      (TFAM) that avidly binds mtDNA and permits efficient targeting into mitochondria
      in situ and in vivo. Thus, the development of gene therapy for treating
      mitochondrial disease offers promise, because it may circumvent the clinical
      abnormalities and the current inability to treat individual disorders in affected
      individuals. This review aims to focus on current treatment options and future
      therapeutics in mitochondrial disease treatment with a special emphasis on
      Leber's hereditary optic neuropathy.

PMID- 23545044
TI  - Challenges in the diagnosis of chronic immune-mediated rheumatic diseases.
AB  - Diagnosing patients with immune-mediated rheumatic diseases has many facets to be
      considered, but early and rapid diagnosis is an important prerequisite for
      correct and straight-forward future management of the patients. For optimal
      results physicians should not miss any diagnosis (assuring high sensitivity of
      the diagnostic process), and high specificity is needed in view of future
      therapeutic interventions. This review focuses on select principal aspects of
      diagnosis in clinical practice: Challenges of diagnostic approaches in immune
      mediated rheumatic diseases include the frequent lack of diagnostic criteria
      (with subsequent misuse of classification criteria), the urgent need for
      diagnostic values of history and further examinations to support diagnosis
      finding strategies, and differential diagnoses to be excluded (e.g., infections
      during early disease and follow-up). First, pure application of classification
      criteria without expert's experience as diagnostic criteria may lead to
      inappropriate diagnoses in 4-32% of all patients with immune-mediated rheumatic
      diseases. Second, sensitivity and specificity data for history and clinical
      examination are necessary not only for routine clinical work, but also for
      purposes of teaching students and learning physicians. Third, conditions to be
      excluded before classification of a certain disease are not necessarily excluding
      a certain diagnosis. Specific interest is given to differentiate infections from
      early onset or relapse of immune-mediated rheumatic diseases.

PMID- 23545045
TI  - Cancer immunotherapy: present status, future perspective, and a new paradigm of
      peptide immunotherapeutics.
AB  - A promising new era of cancer therapeutics with agents that inhibit specific
      growth stimulatory pathways is finding a new niche in our armamentarium in the
      war against cancer. Targeted cancer therapeutics, including humanized monoclonal
      antibodies (mAbs) and tyrosine kinase inhibitors (TKIs), are amongst the major
      treatment options for cancer today together with cytotoxic chemotherapies.
      Targeted therapies are more selective for cancer cells and improve the quality of
      life for cancer patients undergoing treatment. Many of these drugs have been
      approved by the FDA, and several more are being studied in clinical trials.
      Although development of targeted therapeutics has improved cancer treatment
      significantly, the harsh reality is that the "War on Cancer" still exists. Major
      challenges still exist with the currently marketed inhibitors, including
      limitations associated with mAbs and TKIs drug types, acquired mechanisms of drug
      resistance that cause patient relapse, and tumor heterogeneity. Today, there is
      an urgent need for the development of novel anti-tumor agents that are cheaper,
      stable, can selectively target cancer dependent pathways without affecting normal
      cells, and most importantly, avoid development of resistance mechanisms. Peptide
      mimics have the potential benefits of being highly selective, stable, cheap, and
      non-toxic. The focus of this review is to discuss the disadvantages associated
      with the use of monoclonal antibodies and tyrosine kinase inhibitors. A special
      emphasis will be placed on efforts taken in our laboratory to 1) design peptide
      vaccines and therapeutics that target cancer dependent pathways and 2) use a
      combination approach that will shut down alternative mechanisms that lead to
      resistance.

PMID- 23545046
TI  - Therapies for mantle cell lymphoma: current challenges and a brighter future.
AB  - Mantle cell lymphoma (MCL), which accounts for about 6% of non-Hodgkin lymphoma
      (NHL), is characterized by the chromosomal translocation t(11;14)(q13;q32),
      resulting in de-regulated expression of cyclin D1. Managing MCL is challenging,
      because it is incurable with conventional chemotherapy as with indolent NHL, but
      has a more aggressive natural history. Therapeutic advances have been made in the
      past decade with the incorporation of targeted therapies into the frontline
      setting, use of aggressive combination regimens followed by consolidation with
      high dose therapy and autologous stem cell rescue for a younger population, use
      of less aggressive combinations in the elderly, and translation of pre-clinical
      findings to the clinical trial realm with novel agents that hold significant
      promise in the treatment of this disease. The authors review current standard
      approaches in the treatment of MCL, and novel findings in the pathogenesis of
      this disease that may guide the way for further development of modern therapeutic
      approaches.

PMID- 23545048
TI  - How can we trick the immune system into overcoming the detrimental effects of
      oncolytic viral therapy to treat glioblastoma?

PMID- 23545047
TI  - Tumor heterogeneity, clonal evolution, and therapy resistance: an opportunity for
      multitargeting therapy.
AB  - Heterogeneity within the cell population is a feature of many tumors. This lack
      of cellular homogeneity may originate from a number of sources, including
      differential nutrient status due to the de novo microcirculations of tumors, to
      infiltration of normal cells into the tumor, and to the hierarchical natures of
      the cell populations from which cancers arise. Tumors are thought to arise from
      one or more tumor initiating cells (TIC) within the population and to found
      hierarchies of progenitors and more differentiated cancer cells. TIC are often
      derived from tissue stem cells and these cancer stem cells are characterized by
      resistance to most cytotoxic treatments and by a high metastatic rate. Many of
      the properties of tumor populations, including the ability to express mutated
      oncogenes and to evolve new features such as treatment resistance and invasive
      and metastatic potential appear to depend on the molecular chaperone Hsp90. We
      discuss the potential of targeting the heterogeneous cell population with Hsp90
      inhibitory drugs and its potential ability to inactivate TIC and to block the
      evolution of new phenotypes in cancer.

PMID- 23545049
TI  - ADHD and criminality: could treatment benefit prisoners with ADHD who are at
      higher risk of reoffending?

PMID- 23545051
TI  - Primary brain tumors, delta 24 and tumor metabolism. Interview by Rona
      Williamson.
AB  - Interview by Rona Williamson, Commissioning Editor Mark R Gilbert studied
      medicine at the Johns Hopkins School of Medicine in Baltimore (MD, USA). He
      completed residency training in internal medicine and neurology at the Johns
      Hopkins Hospital, then was named the first Keck Foundation Fellow in Neuro
      Oncology at Johns Hopkins. After 2 years on the faculty at Johns Hopkins, he
      moved to the University of Pittsburgh to head the Brain Tumor Program. During his
      tenure at Pittsburgh (PA, USA), he was named Chair of the Brain Tumor Committee
      of the Eastern Cooperative Oncology Group. In 1996, Dr Gilbert moved to the Emory
      University in Atlanta (GA, USA) to lead the Medical Neuro-Oncology Program and
      successfully competed for the program's membership in the New Approaches to Brain
      Tumor Treatment consortium. Dr Gilbert moved to the MD Anderson Cancer Center in
      Houston (TX, USA) in 2000 as Deputy Chair of the Department of Neuro-Oncology.
      During his tenure at MD Anderson, he has created two brain tumor consortia. The
      Collaborative Ependymoma Research Network is an international effort that is
      focusing research efforts on patients, both adult and pediatric, with this
      uncommon central nervous system tumor. The Brain Tumor Trials Collaborative is a
      23-institution consortium that focuses on innovative clinical trials for primary
      glial malignancies. In addition, Dr Gilbert holds a leadership position in the
      Radiation Therapy Oncology Group and has served as the principal investigator on
      several large randomized brain tumor clinical trials. His research focus has been
      in the area of clinical and translational research for primary brain tumors. This
      includes novel clinical trial designs and the integration of correlative tumor
      biology with these clinical studies.

PMID- 23545052
TI  - Genetic and phenotypic variability of optic neuropathies.
AB  - Hereditary optic neuropathies comprise a group of clinically and genetically
      heterogeneous disorders. Two subgroups can be formed: isolated hereditary optic
      atrophies and optic neuropathy as part of complex disorders. In group 1 of
      hereditary optic neuropathies, optic nerve dysfunction is typically the only
      manifestation of the disease. This group comprises autosomal dominant, autosomal
      recessive and X-linked recessive optic atrophy and the maternally inherited
      Leber's hereditary optic neuropathy. Among the autosomal-dominant forms of optic
      atrophy, Kjer's disease is most frequently observed. In the second group of
      complex disorders, various neurologic and other systemic abnormalities are
      regularly observed. Most frequent in this group are mtDNA mutations, inherited
      peripheral neuropathies, Charcot-Marie-Tooth disorders (CMT2A2, CMTX5),
      hereditary sensory neuropathy type 3 (HSAN3), Friedreich's ataxia,
      leukodystrophies, sphingolipidoses, ceroid-lipofuscinoses and neurodegeneration
      with brain iron accumulation. We review current knowledge about the underlying
      genetic predispositions, the most urgent open questions and how this may affect
      our management of this heterogeneous group of disorders in the future.

PMID- 23545053
TI  - Current and future directions for Phase II trials in high-grade glioma.
AB  - Despite surgery, radiation and chemotherapy, the prognosis for high-grade glioma
      (HGG) is poor. Our understanding of the molecular pathways involved in
      gliomagenesis and progression has increased in recent years, leading to the
      development of novel agents that specifically target these pathways. Results from
      most single-agent trials have been modest at best, however. Despite the initial
      success of antiangiogenesis agents in HGG, the clinical benefit is short-lived
      and most patients eventually progress. Several novel agents, multi-targeted
      agents and combination therapies are now in clinical trials for HGG and several
      more strategies are being pursued.

PMID- 23545054
TI  - Pseudoprogression after glioma therapy: a comprehensive review.
AB  - Over the last decade, pseudoprogression as a clinically significant entity
      affecting both glioma patient management and the conduct of clinical trials has
      been recognized as a significant issue. The authors have summarized the
      literature relative to the incidence, chronological sequence, therapy
      relatedness, impact of O-6-methylguanine-DNA methyltransferase methylation status
      and clinical features of pseudoprogression. Evidence regarding numerous
      neuroradiologic techniques to differentiate pseudoprogression from tumor
      recurrence is summarized. The implications of pseudoprogression on prognosis and
      clinical trial design are substantial, and are reviewed. Relative to this, the
      overlapping terms pseudoprogression and radiation necrosis are clarified to
      produce an appropriate basis for future consideration and research regarding this
      important biological phenomenon.

PMID- 23545055
TI  - Clinical trials in cellular immunotherapy for brain/CNS tumors.
AB  - High-grade gliomas are the most common type of primary malignant brain/CNS tumor.
      There have been only modest advances in surgical techniques, radiotherapy and
      chemotherapy for high-grade gliomas over the past several decades. None of these
      have provided a major improvement in survival for patients. Recently,
      immunotherapy has been explored for the treatment of high-grade gliomas.
      Immunotherapy capitalizes on the specificity of the host immune system to
      selectively target tumor cells for destruction, while sparing normal brain
      parenchyma, thus making it a particularly attractive option. This article
      provides a comprehensive review of published clinical trials evaluating cellular
      immunotherapy in primary brain/CNS tumors.

PMID- 23545056
TI  - Individual treatment response in attention-deficit/hyperactivity disorder:
      broadening perspectives and improving assessments.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a highly complex disorder with
      multiple treatment options. Impairments associated with ADHD, rather than
      symptoms defining the disorder, are the primary reason for referral of
      individuals to clinical services; consequently, they should also be key targets
      for intervention. Impairments are moderated by factors such as comorbidities,
      family environment and intelligence quotient, and particular challenges may vary
      between patients. The understanding of patient and family treatment preferences,
      as well as identification of treatment needs and goals, should drive future
      clinical practice. This review addresses the assessment of ADHD treatment goals
      and outcomes in clinical practice, and discusses changes in future clinical
      research studies necessary to progress the utilization of an individualized
      medicine approach in ADHD.

PMID- 23545057
TI  - Genetics of attention-deficit/hyperactivity disorder: current findings and future
      directions.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      affecting 5.29% of children worldwide. It presents a heterogeneous clinical
      expression, and both environmental and genetic factors are involved in the
      etiology. Despite high heritability estimates, identification of genes that
      confer susceptibility to ADHD has been a slow and difficult process. The first
      genetic studies targeted dopaminergic genes, but the effects were small and only
      explained a small portion of ADHD heritability. Recent studies focus on the
      identification of novel genes and pathways that may underlie ADHD. The main goal
      of this review is to present evidence from genome-wide association, copy number
      variation and family-based studies of genetic susceptibility to ADHD. The
      challenges involved to disclose ADHD susceptibility genes will be reviewed in
      order to provide directions for future studies.

PMID- 23545060
TI  - Adolescent fruit and vegetable intake: influence of family support and moderation
      by home availability of relationships with afrocentric values and taste
      preferences.
AB  - Economically disadvantaged African-American adolescents have fruit and vegetable
      (F/V) intakes that are less than optimal. To facilitate intervention planning to
      address low F/V intake in this population, an understanding of determinants of
      youths' intake is needed. The influence of determinants consistently supported by
      evidence (ie, home F/V availability, F/V taste preferences, and parental
      modeling/intake) and variables hypothesized to influence intake in the targeted
      population (ie, family support for F/V consumption and Afrocentric values) were
      examined. Participants were African-American adolescents recruited in 2011
      through summer camps serving low-income youths (N=93). Youths completed a cross
      sectional survey. Hierarchical logistic regression analysis was used to examine
      whether availability directly influenced (ie, explained variations in) intake and
      whether it moderated (ie, affected the direction and/or strength of) the
      relationships between the other hypothesized determinants and intake. The
      dependent variable was intake of five or more daily servings of F/V estimated
      with the Block 7-item food frequency questionnaire. Family support was directly
      related to intake (odds ratio=1.062; 95% CI 1.007 to 1.120; P=0.026). The
      relationships between F/V intake and taste preferences and Afrocentric values
      were moderated by (ie, differed based on) home F/V availability. When
      availability was high, taste preferences (odds ratio=1.081; 95% CI 1.007 to
      1.161; P=0.032) and Afrocentric values (OR=2.504; 95% CI 1.303 to 4.811; P=0.006)
      had positive influences on intake. To enhance intervention effectiveness, more
      research is warranted on approaches for increasing home F/V availability and
      family support for F/V consumption in the targeted population.

PMID- 23545058
TI  - Treatments in context: transcranial direct current brain stimulation as a
      potential treatment in pediatric psychosis.
AB  - Childhood-onset schizophrenia is a chronic, severe form of schizophrenia, and is
      typically treatment resistant. Even after optimized pharmacotherapy, a majority
      (over 70%) of these pediatric patients present lasting psychotic symptoms and
      impaired cognition, necessitating the need for novel treatment modalities. Recent
      work in transcranial magnetic stimulation suggests moderate efficacy in symptom
      reduction in adult patients with schizophrenia; however, the transcranial
      magnetic stimulation treatment is cumbersome for this severely ill population.
      Transcranial direct current stimulation may provide a safe and effective adjuvant
      treatment for continued residual symptoms of schizophrenia.

PMID- 23545061
TI  - A SRCF cell line from snowtrout, Schizothorax richardsonii: development and
      characterization.
AB  - Schizothorax richardsonii, commonly called snowtrout, is an important indigenous
      coldwater fish of the Himalayas, India with high commercial values as food and
      game fish. A cell line named as SRCF was developed from the caudal fin tissue of
      S. richardsonii. The cell line has been maintained in Leibovitz's L-15 medium
      supplemented with 10% fetal bovine serum (FBS) at 24 degrees C. The cells showed
      fibroblastic morphology, high plating efficiency and cell doubling time of 48h.
      Chromosomal analysis of SRCF cells revealed a diploid count of 98 chromosomes.
      The origin of the cell line was confirmed by the amplification of 655 and 578bp
      of cytochrome oxidase subunit I (COI) and 16S rRNA of mitochondrial DNA (mt-DNA)
      genes, respectively. Transfection of SRCF cells with pEGFP-C1 plasmid resulted in
      bright fluorescent signals, suggesting the application of cell line in transgenic
      and genetic improvement programme. In addition, genotoxicity assessment
      illustrated the utility of the cell line as an in vitro model for aquatic
      toxicological studies.

PMID- 23545062
TI  - Nurse-delivered collaborative care for depression and long-term physical
      conditions: a systematic review and meta-analysis.
AB  - BACKGROUND: Depression will be the second largest cause of disease burden by
      2020. It is commonly associated with long term physical health conditions
      resulting in worsened clinical outcome and increased costs. Nurses would appear
      ideally placed to facilitate depression management in those people with long term
      health problems within health care clinics. This article reviews the evidence to
      support such a clinical approach. METHOD: A systematic review and meta-analysis
      of randomised trials of nurse led management of depression in patients with long
      term health problems. Databases were searched between December 2011 and May 2012,
      data were extracted and analysed using Comprehensive Meta Analysis software.
      Subgroup analysis and meta-regression were used to explore the impact of study
      level moderators of effect. RESULTS: Nurse delivered collaborative care was
      compared to usual care in 14 studies including 4440 participants. The mean effect
      size at follow-up was d=0.43 95% CI 0.34 to 0.52 p<0.001 NNT 4.23, representing a
      moderate impact on depression severity. Results were consistent across studies
      and maintained at longer term follow up. LIMITATIONS: Data were only available on
      depression outcomes and with most studies being USA based generalizability is
      somewhat limited. To date only one study reported cost effectiveness outcomes.
      CONCLUSIONS: Based upon the research literature nurse led depression management
      provides effective treatment across a range of long term health conditions.
      Nurses are ideally placed to deliver such interventions and further research is
      required to examine the cost utility of the approach and its durability outside
      of the USA.

PMID- 23545063
TI  - Woodland as working space: where is the restorative green idyll?
AB  - Much has been written on the beneficial, restorative qualities of 'natural' (non
      built) rural or urban 'green' space, including woodland, in promoting mental and
      physical health when accessed for leisure, sport and education. In contrast, with
      the exception of rural health studies, there is relatively little debate about
      the health benefits of 'green space' as work place, especially in woodland and
      forests. In the developed world, this apparent gap in the literature may be
      partly due to an assumption of the forest work place as inherently healthy, and
      also the invisibility of a tiny percentage of the workforce now employed in
      forestry. However, in the UK and parts of Europe over recent years there has been
      a small, though significant, increase in opportunities to train and work in
      woodlands using traditional, sustainable management such as coppicing, and an
      exploration of health issues of woodland work is timely. This paper reports on
      findings from a secondary narrative analysis of oral history interviews selected
      from two phases of the Woodland Recollections Project and newsletters written by
      local people historically and currently engaged in coppicing and woodland work in
      North West England. Perceptions of healthy working in green space are examined by
      applying key concepts of Attention Restoration Theory (ART). Findings suggest
      that woodland work environments involve many counter-restorative factors that can
      render the 'green idyll' detrimental to health and wellbeing. To benefit from
      restorative elements requires drawing on a high level of specialist skills that
      empower individuals to manage and maintain healthy working practices in these
      diverse and challenging environments. 

PMID- 23545064
TI  - (6R,10S)-Pallantione: the first ketone identified as sex pheromone in stink bugs.
AB  - This work describes the structural elucidation of the sex pheromone of the
      soybean stink bug, Pallantia macunaima. The biological activity of the synthetic
      pheromone was demonstrated by behavioral and EAD experiments. Furthermore, the
      absolute configuration of the natural pheromone was determined as (6R,10S)
      6,10,13-trimethyltetradecan-2-one. This is the first ketone identified as a male
      produced sex pheromone in Pentatomidae, and the trivial name, pallantione, was
      assigned to this novel pheromone molecule.

PMID- 23545066
TI  - Perinatal outcomes in preterm growth-restricted twins: effects of gestational age
      and fetal condition.
AB  - OBJECTIVE: To evaluate the perinatal outcome of intrauterine growth-restricted
      preterm twins and contribution of prematurity to morbidity and mortality. STUDY
      DESIGN: A case-control study of 211 preterm twins: 108 growth-restricted twins
      matched with 103 normal growth twins of the same gestational age. Mortality and
      morbidity rates were compared between groups. RESULT: Fetal and overall perinatal
      mortality rates of growth-restricted fetuses were higher than normal growth ones.
      Respiratory distress syndrome incidence was lower and neurologic sequelae
      incidence higher in growth-restricted twins. No differences were observed between
      groups with respect to neonatal mortality, low Apgar score, neonatal intensive
      care unit admission, periventricular hemorrhage, sepsis, jaundice, and
      hematologic or metabolic disorders. CONCLUSION: Adverse perinatal outcomes of
      preterm twins complicated with intrauterine growth restriction are represented by
      a higher antepartum mortality rate, but once born alive, neonatal outcomes seem
      to be associated only with gestational age at birth, excluding a protective
      effect on lung maturation and a higher risk of long-term neurologic sequelae.

PMID- 23545067
TI  - Age-related mitochondrial alterations without neuronal loss in the hippocampus of
      a transgenic model of Alzheimer's disease.
AB  - The Tg2576 mouse, which carries the Swedish mutant form of human beta-amyloid
      precursor protein (hAPP(swe)), develops Alzheimer's Disease (AD)-like phenotype
      (synaptic pathology, cognitive impairment and beta amyloid -Abeta- plaques.) in
      the absence of significant neuronal loss. We have analyzed the hippocampal
      proteome of Tg2576, focusing on changes at 7 months of age, when Abeta levels
      begin to increase but cognitive symptoms are still not evident, and at 16 months,
      when most AD-like features are manifested. Proteins differentially expressed with
      respect to wild-type animals were grouped according to their biological function
      and assessed in the context of AD. Metabolic enzymes, propionyl- CoA carboxylase,
      which has not been previously related to AD, and glutamine synthetase, which is a
      key enzyme for ammonium removal, were among deregulated proteins. Mitochondria of
      young animals have to cope with the metabolic stress and elevated ATP demand
      caused by overexpression of hAPP(swe). Significantly, a large number of
      mitochondrial proteins (16, 28% of the total) were deregulated in young Tg2576
      mice and seven of them were found at normal levels in aged animals. Mitochondrial
      dysfunction in 7-month-old mice was confirmed by reduction in the inner membrane
      integrity and increase in the activity of cytochrome c oxidase. The proteome
      analysis indicates that mitochondrial and overlapping metabolic alterations are
      adaptive upon aging, and may explain the synaptic pathology and cognitive
      impairment in the absence of neuronal loss. Animal models such as 7-month-old
      Tg2576 mice and tools to investigate synaptic alterations before appearance of
      neuronal death may help in understanding the pathological mechanisms occurring at
      early stages of AD.

PMID- 23545068
TI  - Activity of Bacillus thuringiensis cyt1Ba crystal protein against hymenopteran
      forest pests.
AB  - A crystal-spore suspension of PS201T6 was toxic to larvae of Diprion similis
      (Hymenoptera: Diprionidae). Toxicity was at least in part attributable to the
      Cyt1Ba crystal protein, as demonstrated by bioassays of solubilized protein
      produced by Escherichia coli expressing PS201T6's cyt1Ba gene. PS201T6 reduced
      survival and growth of D. similis in a 2-week field experiment. In laboratory
      bioassays, both toxin and parental strain affected Acantholyda erythrocephala
      (Pamphiliidae), Pikonema alaskensis (Tenthredinidae), and Neodiprion sertifer
      (Diprionidae), as well as spruce budworm, Choristoneura fumiferana (Lepidoptera:
      Tortricidae). Affecting insects across at least four orders (Diptera, Coleoptera,
      Hymenoptera, Lepidoptera), Cyt1Ba has the broadest insecticidal activity spectrum
      among Bacillus thuringiensis crystal proteins documented to date.

PMID- 23545069
TI  - Performance of submerged membrane bioreactor (SMBR) with and without the addition
      of the different particle sizes of GAC as suspended medium.
AB  - In this study the effect of different particle sizes of granular activated carbon
      (GAC) on the performance of a submerged membrane bioreactor (SMBR) was
      investigated. The sizes of GAC used were 150-300, 300-600 and 600-1200 MUm. The
      SMBR was operated at a filtration flux of 20 L/m(2)h. The removal of dissolved
      organic carbon (DOC) and chemical oxygen demand (COD) with the addition of GAC
      was 95%. The concentration of biopolymers, humic, building block and low
      molecular weight neutral and acids in the SMBR effluent was reduced by 20%, 66
      76%, 20-50%, 30-56%, respectively. It helped to reduce the sludge volume index
      (SVI) and transmembrane pressure (TMP) development by 30-40% and 58%,
      respectively. However, the removal of NH4(+) and PO4(3-) was relatively low of 35
      45% and 34-43%, respectively. The SMBR effluent was rich in PO4(3-) and was
      removed/recovered using hydrated ferric oxide (HFO). The removal of PO4(3-) was
      almost 90%.

PMID- 23545070
TI  - Coupling reactions of trehalose synthase from Pyrococcus horikoshii: cost
      effective synthesis and anti-adhesive activity of alpha-galactosyl
      oligosaccharides using a one-pot three-enzyme system with trehalose.
AB  - A new sugar nucleotide cycling (SNC) process was established in a one-pot three
      enzyme-coupled reaction using disaccharide trehalose. Trehalose synthase from
      Pyrococcus horikoshii could be applied to the SNC process for the synthesis of
      functional alpha-galactosyl oligosaccharides, alpha-galactose (Gal) epitopes and
      globotriose, using the effective regeneration of UDP-Gal. The alpha-Gal epitopes
      and globotriose were found to attach to the cell-surface of enteropathogenic
      Escherichia coli O127 (EPEC) which were bound to human Caco-2 cells. These alpha
      galactosyl oligosaccharides were able to prohibit the attachment of EPEC, which
      could have resulted in colonization and disease. The alpha-Gal epitope III with a
      lactulose acceptor showed the most inhibitory activity of anti-adhesion. The
      results suggest that the alpha-galactosyl oligosaccharides may be alternative
      anti-adhesion molecules that overcome antibiotic resistance.

PMID- 23545071
TI  - Effects of light availability on the biomass production, CO2 fixation, and
      bioethanol production potential of Thermosynechococcus CL-1.
AB  - A thermophilic cyanobacterium named Thermosynechococcus CL-1 (TCL-1) was
      cultivated in this study to eliminate the energy input of cooling system in flat
      plate photobioreactors. Cultivating TCL-1 in the 1.5 cm light path flat plate
      photobioreactor exhibited stable characteristics for biomass production, CO2
      fixation, and carbohydrate production under high illumination conditions (1000 or
      2000 MUE m(-2) s(-1)). The greatest biomass and carbohydrate productivity, and
      CO2 fixation rate were recorded at 116, 67, and 170 mg/L/h, respectively, in the
      1.5c m light path photobioreactor and under optimal biomass concentration (about
      3 g/L). Cultivating Thermosynechococcus CL-1 in flat plate photobioreactors
      exhibits high potential for biomass production, CO2 fixation and bioethanol
      production.

PMID- 23545072
TI  - Evaluating consistency in the interpretation of NTP rodent cancer bioassays: an
      examination of mouse lung tumor effects in the 4-MEI study.
AB  - The potential carcinogenicity of 4-methylimidazole (4-MEI) was evaluated in a
      National Toxicology Program (NTP) rodent cancer bioassay in Fischer 344 rats and
      B6C3F1 mice (NTP, 2007; Chan et al., 2008). The NTP concluded that there was
      "clear evidence of carcinogenic activity" in male and female mice, based on an
      increased incidence of lung tumors. The "category of evidence" that the NTP
      assigns to a rodent cancer bioassay outcome can have significant regulatory
      implications. This is especially important for 4-MEI, which forms in caramel
      colorings and other foods during cooking, with potential widespread human
      exposure in a broad spectrum of food and beverage products. A detailed analysis
      of all NTP mouse-lung-tumor-only carcinogens reveals that the proper call for
      lung tumors in the 4-MEI study should have been "some evidence" rather than
      "clear evidence" of carcinogenic activity for both male and female mice in order
      to be consistent with the NTP's interpretation of other mouse lung carcinogens
      showing a similar strength of response. Suggestions are given as to measures the
      NTP should consider in the preparation of some or all future Technical Reports in
      order to enhance consistency of interpretation of experimental results.

PMID- 23545073
TI  - The importance of problem formulations in risk assessment: a case study involving
      dioxin-contaminated soil.
AB  - The need to remediate contaminated soils is typically accomplished by applying
      standard risk assessment methods followed by risk management to select remedial
      options. These human health risk assessments (HHRAs) have been largely conducted
      in a formulaic manner that relies heavily on standard deterministic exposure,
      toxicity assumptions and fixed mathematical formulas. The HHRA approach, with its
      traditional formulaic practice, does not take advantage of problem formulation in
      the same manner as is done in ecological risk assessment, and historically, has
      generally failed to emphasize incorporation of site-specific information. In
      response to these challenges, the National Academy of Sciences recently made
      several recommendations regarding the conduct of HHRAs, one of which was to begin
      all such assessments with problem formulation. These recommendations have since
      been extended to dose response assessment. In accordance with these
      recommendations, a group of experts presented and discussed findings that
      highlighted the importance and impact of including problem formulation when
      determining the need for remediation of dioxin contamination in soils, focusing
      in particular on exposure assessment is described.

PMID- 23545074
TI  - Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in
      feeding- and reward-related brain areas of young OLETF rats.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in
      brain areas involved in the control of appetite, drug reward and homeostatic
      regulation and it has an overall anorexigenic effect. Recently, we have shown
      that CART peptide immunoreactivity was significantly reduced in the rostral part
      of the nucleus accumbens and in the rostro-medial part of the nucleus of the
      solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans
      Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean
      controls. It is not clear, however, whether altered CART expression is caused
      primarily by the deficiency in CCK-1 signaling or whether is related to the obese
      and diabetic phenotype of the OLETF strain which develops at a later age.
      Therefore, in the present study, CART-immunoreaction in feeding-related areas of
      the brain was compared in young, age-matched (6-7 weeks old) non-obese, non
      diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic
      OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and
      axons throughout the brain when compared to age-matched LETO rats. In contrast to
      previous results observed in the obese diabetic adult rats, intensity of CART
      immunoreaction did not differ in the areas related to control of food-intake and
      reward in the young OLETFs compared to young LETO rats. Our findings suggest that
      factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor
      signaling may contribute to altered CART expression in the OLETF strain.

PMID- 23545075
TI  - Optimal continuous-monitoring design of single-arm phase II trial based on the
      simulated annealing method.
AB  - Simon's two-stage design is commonly used in phase II single-arm clinical trials
      because of its simplicity and smaller sample size under the null hypothesis
      compared to the one-stage design. Some studies extend this design to accommodate
      more interim analyses (i.e., three-stage or four-stage designs). However, most of
      these studies, together with the original Simon's two-stage design, are based on
      the exhaustive search method, which is difficult to extend to high-dimensional,
      general multi-stage designs. In this study, we propose a simulated annealing (SA)
      based design to optimize the early stopping boundaries and minimize the expected
      sample size for multi-stage or continuous monitoring single-arm trials. We
      compare the results of the SA method, the decision-theoretic method, the
      predictive probability method, and the posterior probability method. The SA
      method can reach the smallest expected sample sizes in all scenarios under the
      constraints of the same type I and type II errors. The expected sample sizes from
      the SA method are generally 10-20% smaller than those from the posterior
      probability method or the predictive probability method, and are slightly smaller
      than those from the decision-theoretic method in almost all scenarios. The SA
      method offers an excellent alternative in designing phase II trials with
      continuous monitoring.

PMID- 23545076
TI  - What do non-randomized trials offer above and beyond randomized trials?

PMID- 23545077
TI  - Emotional reactivity at 12 months in very preterm infants born at <29 weeks of
      gestation.
AB  - The present study evaluated the socio-emotional development of very preterm born
      infants at 12 months corrected age. Forty-one infants born very preterm (<29
      weeks of gestation) were compared to 22 infants born full term on a standardized
      behavioral assessment and a parental temperament questionnaire, both measuring
      emotional reactivity to joy, anger and fear, as well as sustained attention. The
      behavioral assessment showed that very preterm infants exhibited as much joy as
      full term infants during a joy-eliciting episode. However, they expressed a
      significantly higher reactivity in anger-eliciting situations and a reduced
      reactivity toward fear-eliciting situations. For all three emotion-eliciting
      situations, the preterm infants reacted with a higher level of motor activity.
      The preterm infants also exhibited a distinct attention pattern with a
      significantly higher initial attention level which declined rapidly throughout
      the episode. The questionnaire did not show any group differences. The clinical
      relevance of these results in terms of preliminary hallmarks of later behavioral
      difficulties such attention deficit/hyperactivity disorder are discussed as well
      as the inconsistencies observed between the questionnaire and the behavioral
      assessment.

PMID- 23545078
TI  - Infant functional regulatory problems and gender moderate bidirectional effects
      between externalizing behavior and maternal depressive symptoms.
AB  - This longitudinal study of 251 families examined bidirectional associations
      between maternal depressive symptoms and toddler behavioral problems. Functional
      regulatory problems in infancy and gender were examined as moderators. Mothers
      rated children's regulatory problems of crying, feeding, and sleeping in infancy,
      toddler-age externalizing behavior, and their own depressive symptoms when
      children were ages 7, 15, and 33 months. Using a structural equation model we
      found that exposure to maternal depressive symptoms at 7 months predicted high
      levels of child externalizing behavior at 15 and 33 months. Gender moderated the
      effect, such that maternal depressive symptoms only predicted boys' externalizing
      behavior at 33 months. Toddler-age externalizing behavior predicted high levels
      of maternal depressive symptoms at 33 months, only among those who had relatively
      few regulatory problems as infants. Infancy seems to be a period of heightened
      vulnerability to effects of maternal depression and boys are more likely than
      girls to develop resulting externalizing problems. Mothers of infants with few
      regulatory problems may develop worse depressive symptoms in response to their
      children's preschool-age behavioral problems.

PMID- 23545079
TI  - Imaging 3.0: what is it?

PMID- 23545080
TI  - The 2012 JACR readership survey.

PMID- 23545081
TI  - The threat to radiologists from the multiple-procedure payment reduction.

PMID- 23545082
TI  - A tale of two exchanges.

PMID- 23545083
TI  - IT: from complement to substitute.

PMID- 23545084
TI  - Professional norms regarding how radiologists handle incidental findings.
AB  - The author reviews the dilemmas posed by incidental radiologic findings and
      provides an analysis of factors that underlie how radiologists handle them.
      Particular attention is paid to professional standards that mediate clinical
      decision making and communication in the setting of risk. The author concludes
      that individual radiologists should report the incidental findings they detect
      and use existing evidence-based recommendations when possible. Such
      recommendations, however, face their own challenge in maintaining consistency
      with norms around risk-related decision making in other clinical realms.

PMID- 23545085
TI  - A hospital CEO's perspective: radiology should lead the way in reforming health
      care delivery.
AB  - Radiology and medical imaging systems play a central role in most health care
      systems. As science and technology have advanced, the ability to medically image
      and diagnose anatomic and physiologic pathology has increased exponentially. This
      capability is identified as a necessary core competency of all "general
      hospitals" by the American Hospital Association. Medical imaging accounts for
      7.5% of health care spending in the United States, with $175 billion spent
      annually. Accordingly, the facilities and the physicians who provide this patient
      care will be a central focus in the crusade for patient-centered, efficient, and
      transportable patient care. As the demand in hospitals and health care systems
      for quality, safety, and efficiency through IT and clinical systems improvement
      continues to accelerate, the demand for more systems that use best-practice
      support and discrete data results for incorporation into systems reporting
      initiatives will also accelerate and grow. Medical imaging and the radiologist's
      report are central to creating this integrated, patient-centric system with
      hospitals. Ancillary to the patient care component of the functional use of the
      data reporting systems is the ability to use the clinical reporting information
      efficiently to support or defend clinical decisions associated with hospital care
      and to provide an improved means by which required quality metrics are made
      available for ensuring safety and improving care in the future.

PMID- 23545086
TI  - Utilization of dashboard technology in academic radiology departments: results of
      a national survey.
AB  - PURPOSE: The aim of this study was to identify the most widely used financial,
      productivity, and accessibility metrics used by academic radiology departments
      (ARDs) in a dashboard format via a national survey. The results provide a guide
      to the selection of preferred or commonly used indicators to facilitate dashboard
      implementation and use. METHODS: The study met the criteria for an exemption from
      institutional review board approval. A cross-sectional survey was conducted using
      a survey approved by the Society of Chairs of Academic Radiology Departments and
      sent to its members. The survey was designed to evaluate the adoption, access,
      and composition of dashboard technology in ARDs, particularly those related to
      measures of productivity and financial performance. RESULTS: The overall response
      rate was 42% (56 of 131 members). Sixty-two percent of responding ARDs currently
      use some form of dashboard technology, but 50% have used this technology for <=2
      years. Sixty-five percent of all ARDs use their dashboard information on a
      monthly basis. The two dashboard financial indicators most frequently used by
      ARDs are revenue and actual expenses. Similarly, the two productivity indicators
      used most widely are total examination volume and examination volume per
      modality. The two most important access indicators used are report turnaround
      time and backlog per unit time. CONCLUSIONS: Currently, fewer than two-thirds of
      the responding ARDs use dashboard technology, and one-half have used the
      technology for <=2 years. Although some fiscal and productivity indices are more
      frequently used, there are a diverse number of factors used to measure
      productivity, finance, access, and other operational parameters in ARD
      dashboards. Thus, the information provided by each institutional dashboard may be
      significantly different from that in other ARDs.

PMID- 23545087
TI  - Naturally Leishmania infantum-infected dogs display an overall impairment of
      chemokine and chemokine receptor expression during visceral leishmaniasis.
AB  - Dogs are the primary reservoir for Leishmania parasites. The immune response
      induced by Leishmania infantum infection in these animals has not been completely
      elucidated, and few studies have investigated the relationship between the
      expression levels of chemokines and chemokine receptors and the clinical status
      of dogs with canine visceral leishmaniasis (CVL). The aim of this study was to
      correlate the clinical status of naturally L. infantum-infected dogs (from rural
      areas of Mossoro city, State of Rio Grande do Norte, Brazil) with the expression
      levels of chemokines (ccl1, ccl2, ccl3, ccl4, ccl5, ccl17, ccl20, ccl24, ccl26,
      cxcl9, cxcl10) and chemokine receptors (cxcr3, ccr3, ccr4, ccr5, ccr6, ccr8) in
      the liver and spleen determined using real-time PCR. Twenty-one dogs were
      clinically evaluated and classified as asymptomatic (n=11) or symptomatic (n=10).
      Splenomegaly, weight loss and onychogryphosis were the most pronounced symptoms.
      In the liver, the mRNA expression levels of ccl1, ccl17, ccl26, ccr3, ccr4, ccr5,
      ccr6, and ccr8 were lower in symptomatic animals than in asymptomatic animals.
      Compared with uninfected animals, symptomatic dogs had lower expression levels of
      almost all molecules analyzed. Moreover, high clinical scores were negatively
      correlated with ccr5 and ccr6 expression and positively correlated with cxcl10
      expression. We conclude that the impairment of the expression of chemokines and
      chemokine receptors results in deficient leukocyte migration and hampers the
      immune response, leading to the development of disease.

PMID- 23545088
TI  - Impregnation of implantable polypropylene mesh with S-nitrosoglutathione-loaded
      poly(vinyl alcohol).
AB  - Clinical complications of implantable polypropylene (PP) meshes used to repair
      urinary incontinence and vaginal prolapse may be associated with their low
      surface energy and consequent poor tissue integration. For improving tissue
      integration, we impregnated monofilament PP meshes with physically crosslinked
      poly(vinyl alcohol) (PVA), resulting in PVA deposits tightly attached inside the
      knot spaces of the PP knit. While preserving the mesh porosity, the PVA deposits
      acted as an array of hydrophilic regions leading to a great increase in the
      overall mesh wettability, reflected by a contact angle decrease from 111 to ca.
      66 degrees . The PVA deposits were also used as reservoirs for the local release
      of S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor. Plain and impregnated
      PP meshes (1.0cm*1.0cm) were implanted in the subcutaneous tissue of 21 adult
      female Wistar rats. Histological analysis of the abdominal wall 21 days after the
      surgeries revealed lower edema and greater angiogenesis while a marked decrement
      of NOx concentration in the tissue surrounding the impregnated meshes was
      observed after 2 days. These results indicate that PVA and PVA/GSNO impregnation
      might be a new strategy for decreasing the frequency of mesh extrusion after PP
      mesh implants.

PMID- 23545089
TI  - Production and structural characterization of biosurfactant produced by an
      alkaliphilic bacterium, Klebsiella sp.: evaluation of different carbon sources.
AB  - The potential of an alkaliphilic bacterium Klebsiella sp. strain RJ-03, to
      utilize different carbon sources for the production of an extracellular
      biosurfactant was evaluated. Among the several carbon substrates tested,
      production of the crude biosurfactant was found to be the highest with starch
      (10.1+/-0.11g/L) followed by sucrose (5.1+/-0.11g/L), xylose (3.25+/-0.08g/L),
      galactose (3.1+/-0.16g/L) glucose (2.75+/-0.11g/L) and fructose (2.62+/-0.07g/L).
      The crude biosurfactant production was done using starch, sucrose, xylose,
      galactose and glucose containing medium, that exhibited significantly high
      viscosity, emulsification activity and maximum reduction in surface tension as
      compared to those obtained from fructose and maltose. The carbon source has
      significant effect on the quantity as well as the quality of biosurfactant
      production. The chemical characteristics of purified biosurfactant was compared
      by NMR, FT-IR, SEM, GPC, MALDI TOF-TOF MS, GC-MS, TG and DSC analysis, indicating
      variation in the functional groups, bonds, elements, monosaccharide composition,
      molecular mass and thermo stability.

PMID- 23545090
TI  - Palladium(II)-catalyzed ortho-olefination of benzylic phosphonic monoesters.
AB  - The new monophosphonic acid directing group is successfully utilized in the
      Pd(II)-catalyzed ortho-olefination of benzylic phosphonic monoesters and offers
      further development of other phosphoryl-related directing groups in the
      transition-metal-catalyzed C-H activations.

PMID- 23545091
TI  - Typical and atypical metastatic sites of recurrent endometrial carcinoma.
AB  - The purpose of this article is to illustrate the imaging findings of typical and
      atypical metastatic sites of recurrent endometrial carcinoma. Typical sites
      include local pelvic recurrence, pelvic and para-aortic nodes, peritoneum, and
      lungs. Atypical sites include extra-abdominal lymph nodes, liver, adrenals,
      brain, bones and soft tissue. It is important for radiologists to recognize the
      typical and atypical sites of metastases in patients with recurrent endometrial
      carcinoma to facilitate earlier diagnosis and treatment.

PMID- 23545092
TI  - Spot stenting of the tear in type B aortic dissection.
AB  - BACKGROUND: In selected type B acute aortic dissection with aortic growth and
      patent false lumen, an intervention may be required to prevent aortic rupture.
      Apart from stent grafting of the thoracic aorta, aimed at occluding the primary
      intimal tear, some have advocated closure of reentry tears by stent grafting of
      the aortic true lumen after hybrid revascularization of the excluded viscera or
      by branched aortic endografts. METHODS: We describe a simple technique for
      occluding a major reentry tear in the visceral abdominal aorta, using on-the
      shelf covered stent grafts, arising from the aortic true lumen, crossing the
      dissection septum tear and aortic false lumen, and being distally anchored in the
      visceral branch vessel, acting as a rivet on the dissection septum tear,
      achieving aortic false lumen thrombosis. RESULTS: In selected cases, we achieved
      aortic false lumen thrombosis by spot stenting of the tear. CONCLUSIONS: This
      spot stenting technique may be a useful way of achieving complete false lumen
      thrombosis or lowering the false lumen pressure of degenerating dissecting
      aneurysms.

PMID- 23545093
TI  - Persistent type B aortic dissection treatment by renal artery reentry stent
      grafting as an alternative to open surgery.
AB  - Type B aortic dissections complicated by pain, malperfusion, or aneurysm
      expansion mandate surgical intervention. Success of this therapy is predicated on
      exclusion and thrombosis of the false lumen of the aneurysm. This report presents
      a case in which cessation of flow was achieved using a covered stent graft to
      close a renal reentry tear after a previous closing and overstenting of the main
      tear. This approach may provide a helpful adjunct to the endovascular treatment
      of complicated type B aortic dissections.

PMID- 23545094
TI  - Rapid development of aneurysmal formation after successful endovascular treatment
      of chronic total occlusion of a persistent sciatic artery.
AB  - Persistent sciatic artery (PSA) is a rare congenital anomaly that is frequently
      complicated by atherosclerotic changes, such as occlusion and aneurysmal
      formation. This report describes a case of a chronic total occlusion (CTO) of a
      unilateral, complete-type PSA in the right thigh of a 74-year-old woman that was
      treated successfully with endovascular angioplasty and stent placement. Within 3
      months, however, a PSA aneurysm developed in the gluteal region. This aneurysm
      was repaired endovascularly through placement of a stent graft. To the authors'
      knowledge, rapid formation of a PSA aneurysm and successful endovascular
      treatment of both CTO of a PSA and of a PSA aneurysm have not been reported
      previously.

PMID- 23545095
TI  - Trajectory of illness for patients with congestive heart failure.
AB  - BACKGROUND AND OBJECTIVE: This study describes progression to death for patients
      with congestive heart failure (CHF). METHODS: We used SAS procedure Proc Traj to
      fit a semiparametric model to longitudinal data on prognosis of patients with CHF
      in the 12 months prior to death. Data were collected on 744 patients with CHF in
      2010 at Bay Pines VA Healthcare System; 386 subjects had sufficient data points
      (minimum of five encounters) to trace their risk in 12 months prior to death. The
      prognosis of the patient was calculated using the comorbidities of the patient.
      RESULTS: Unexpected death occurred in 20.5% of patients; all remaining patients
      had a gradual progression toward death. For 13.3% of patients, progression toward
      death started 12 months prior to death. For 29.9% of patients, increased risk
      started at 6 months prior to death. For 36.3% of patients, it started 3 months
      prior to death. One month prior to death, 79.5% of the patients had a more than
      97% chance of mortality. It may be possible to use progression toward death over
      3 consecutive months as a predictor of need for hospice consultation.
      CONCLUSIONS: Five typical illness trajectories have been described for patients
      with progressive heart failure. The needs of patients and their caregivers are
      likely to vary according to the trajectory patients are following. Contrary to
      reports in the literature about unexpected death in patients with CHF, the
      majority of decedents in our study had a predictable and gradual progression
      toward death. Recognizing these trajectories may help clinicians implement an
      appropriate plan to meet the needs of patients and their caregivers.

PMID- 23545096
TI  - Executive functioning and psychopathological profile in relatives of individuals
      with deficit v. non-deficit schizophrenia: a pilot study.
AB  - Aims. Heterogeneity of schizophrenia is known to be reflected in
      neuropsychological functioning of patients, but its expression in relatives is
      understudied. This study aims at exploring relationship between executive
      functioning and clinical profiles of first-degree relatives of patients who are
      classified as having or not having the deficit subtype of schizophrenia (DSRELs
      v. non-DSRELs), with the prediction of greater executive impairment in DSRELs.
      Methods. DSRELs (n = 15) and non-DSRELs (n = 40) were compared with community
      controls (CCs, n = 55) on executive functioning measured by the Wisconsin Card
      Sorting Test (WCST) and the phonemic verbal fluency (PVF), and clinical measures.
      Effects of psychopathology and intelligence quotient (IQ) measures were
      investigated to determine their association with executive performance. Results.
      DSRELs showed more executive dysfunction on WCST and poorer social functioning
      than CCs and more severe negative symptoms than non-DSRELs. Differences on WCST
      categories achieved (WCST-CA) remained significant after adjustment for clinical
      confounders and IQ. WCST-CA was associated with apathy and paranoid ideation only
      within the DSREL subgroup. Conclusions. Executive functioning and negative
      symptoms are severely impaired in first-degree relatives of deficit syndrome
      patients, thus suggesting that some neurocognitive deficits in patients may be
      transmitted within families according to the pathophysiology of the probands. 

PMID- 23545097
TI  - Presence of phosphodiesterase type 5 in the spinal cord and its involvement in
      bladder outflow obstruction related bladder overactivity.
AB  - PURPOSE: Phosphodiesterase type 5 inhibitors were recently introduced as a new
      treatment option for men with lower urinary tract symptoms. Safety and clinical
      effectiveness are well documented but the mode of action is still unclear. We
      determined and compared the expression of phosphodiesterase type 5 in the spinal
      cord of normal (sham operated) rats and rats with partial urethral obstruction
      induced bladder overactivity. We also assessed the urodynamic effects of
      intravenously and intrathecally administered sildenafil in the rats to determine
      whether phosphodiesterase type 5 inhibitors exert effects on the sacral spinal
      cord. MATERIALS AND METHODS: A total of 65 male Sprague-Dawley rats were used for
      molecular/morphological and functional experiments. Bladder overactivity was
      induced via surgical partial urethral obstruction in 39 of 65 rats. Spinal
      phosphodiesterase type 5 expression was assessed by histology and polymerase
      chain reaction. The effects of sildenafil administered intravenously or
      intrathecally were studied urodynamically. RESULTS: Phosphodiesterase type 5 was
      expressed in various regions of the lumbosacral spinal cord, including the sacral
      regions of micturition control. Expression was similar in normal rats and rats
      with partial urethral obstruction/bladder overactivity. In normal rats
      intravenous and intrathecal sildenafil had no urodynamic effect. When
      administered intravenously and intrathecally to rats with partial urethral
      obstruction/bladder overactivity, sildenafil decreased micturition frequency and
      bladder pressure. Doses tested intrathecally had no effect when given
      intravenously. CONCLUSIONS: Phosphodiesterase type 5 is expressed in the rat
      spinal cord. Intravenous sildenafil may exert part of its urodynamic effect in
      rats with partial urethral obstruction/bladder overactivity via an effect on the
      sacral spinal cord.

PMID- 23545098
TI  - Dysfunctional elimination syndromes--how closely linked are constipation and
      encopresis with specific lower urinary tract conditions?
AB  - PURPOSE: It is recognized that there is a strong association between bladder and
      bowel dysfunction. We determined the association of constipation and/or
      encopresis with specific lower urinary tract conditions. MATERIALS AND METHODS:
      We reviewed our database of children with lower urinary tract dysfunction and
      divided cases into 3 categories of bowel dysfunction (constipation, encopresis
      and constipation plus encopresis) and 4 lower urinary tract conditions
      (dysfunctional voiding, idiopathic detrusor overactivity disorder, detrusor
      underutilization disorder and primary bladder neck dysfunction). Associations
      between bowel dysfunction types and each lower urinary tract condition were
      determined. RESULTS: Of 163 males and 205 females with a mean age of 8.5 years
      constipation was the most common bowel dysfunction (27%). Although encopresis is
      generally thought to reflect underlying constipation, only half of children with
      encopresis in this series had constipation. Dysfunctional voiding was associated
      with the highest incidence of bowel dysfunction. All but 1 patient with
      encopresis had associated urgency and detrusor overactivity, and the encopresis
      resolved in 75% of patients after initiation of anticholinergic therapy.
      Constipation was significantly more common in girls (27%) than in boys (11%, p
      <0.01), while encopresis was more common in boys (9%) than in girls (3%, p =
      0.02), likely reflecting the higher incidence of dysfunctional voiding in girls
      and idiopathic detrusor overactivity disorder in boys. CONCLUSIONS: Active bowel
      dysfunction was seen in half of the children with a lower urinary tract
      condition. Constipation was more common in patients with dysfunctional voiding,
      while encopresis was significantly increased in those with idiopathic detrusor
      overactivity disorder and in those with dysfunctional voiding, severe urgency and
      detrusor overactivity. Anticholinergics, despite their constipating effect, given
      for treatment of detrusor overactivity resolved encopresis in most children with
      this bowel dysfunction.

PMID- 23545099
TI  - Comparative effectiveness review: prostate cancer antigen 3 testing for the
      diagnosis and management of prostate cancer.
AB  - PURPOSE: We compared the effectiveness of PCA3 (prostate cancer antigen 3) and
      select comparators for improving initial or repeat biopsy decision making in men
      at risk for prostate cancer, or treatment choices in men with prostate cancer.
      MATERIALS AND METHODS: MEDLINE(r), EMBASE(r), Cochrane Database and gray
      literature were searched from January 1990 through May 2012. Included studies
      were matched, and measured PCA3 and comparator(s) within a cohort. No matched
      analyses were possible. Differences in independent performance estimates between
      PCA3 and comparators were computed within studies. Studies were assessed for
      quality using QUADAS (Quality Assessment of Diagnostic Accuracy Studies) and for
      strength of evidence using GRADE (Grading of Recommendations Assessment,
      Development and Evaluation) criteria. RESULTS: Among 1,556 publications
      identified, 34 observational studies were analyzed (24 addressed diagnostic
      accuracy and 13 addressed treatment decisions). Most studies were conducted in
      opportunistic cohorts of men referred for procedures and were not designed to
      answer key questions. Two study biases (partial verification and sampling) were
      addressed by analyses, allowing some conclusions to be drawn. PCA3 was more
      discriminatory than total prostate specific antigen increases (eg at an observed
      50% specificity, summary sensitivities were 77% and 57%, respectively). Analyses
      indicated that this finding holds for initial and repeat biopsies, and that the
      markers were independent predictors. For all other biopsy decision making
      comparisons and associated health outcomes, strength of evidence was
      insufficient. For treatment decision making, strength of evidence was
      insufficient for all outcomes and comparators. CONCLUSIONS: PCA3 had a higher
      diagnostic accuracy than total prostate specific antigen increases, but strength
      of evidence was low (limited confidence in effect estimates). Strength of
      evidence was insufficient to conclude that PCA3 testing leads to improved health
      outcomes. For all other outcomes and comparators, strength of evidence was
      insufficient.

PMID- 23545100
TI  - Expression and functional role of Cdx2 in intestinal metaplasia of cystitis
      glandularis.
AB  - PURPOSE: Cdx2 is an essential transcription factor in intestinal epithelial cell
      differentiation and proliferation. However, to our knowledge the expression and
      role of Cdx2 in the development of intestinal cystitis glandularis, a metaplastic
      lesion induced by chronic inflammation, remained to be explored. MATERIALS AND
      METHODS: Real-time polymerase chain reaction was used to examine Cdx2, LI
      cadherin and villin expression in typical and intestinal cystitis glandularis,
      and normal bladder tissue. Cdx2 cDNA was subcloned to the retroviral vector
      pLNCX2 for subsequent transfection into human bladder urothelium cells and rat
      bladder urothelium. Cdx2 mRNA and protein levels, and cell morphology and
      proliferation were assessed after transfection using real-time polymerase chain
      reaction, phase contrast microscopy, transmission electron microscopy and MTT
      assay, respectively. RESULTS: Higher mRNA levels of Cdx2, villin and LI-cadherin
      were detected in intestinal cystitis glandularis compared to normal bladder and
      typical cystitis glandularis. Only Cdx2 groups attained statistical significance
      (p <0.001). Retroviral over expression of Cdx2 resulted in increased mRNA and
      protein expression of Cdx2 as well as villin and LI-cadherin levels, and
      increased cell proliferation. A distinct change in cellular morphology, in which
      cells resembled intestinal-like cells, was also observed in vitro and in vivo.
      CONCLUSIONS: Cdx2 may have a critical role in regulating intestinal metaplasia in
      cystitis glandularis. Further studies are planned to assess the potential of
      using Cdx2 as a marker and therapeutic target for cystitis glandularis.

PMID- 23545101
TI  - The impact of intravesical gemcitabine and 1/3 dose Bacillus Calmette-Guerin
      instillation therapy on the quality of life in patients with nonmuscle invasive
      bladder cancer: results of a prospective, randomized, phase II trial.
AB  - PURPOSE: Bacillus Calmette-Guerin and intravesical chemotherapy represent viable
      adjuvant options for intermediate risk nonmuscle invasive bladder cancer.
      Although bacillus Calmette-Guerin is perceived as less tolerable than
      intravesical chemotherapy, to our knowledge no comparative studies have addressed
      quality of life issues. We compared the quality of life of patients with
      nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine
      or 1/3 dose bacillus Calmette-Guerin. MATERIALS AND METHODS: Our multicenter,
      prospective, randomized, phase II study included 120 patients with intermediate
      risk nonmuscle invasive bladder cancer. Of these patients 88 remained assessable
      at 1-year followup. Only 1 patient was withdrawn because of adverse events.
      Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks
      (maintenance monthly for 1 year) while 59 received 1/3 dose bacillus Calmette
      Guerin Connaught weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6
      and 12 months). Quality of life was measured by the EORTC QLQ-C30 (European
      Organization for the Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30 version 3.0) and QLQ-BLS24 (Quality of Life Superficial
      Bladder Cancer-Specific 24) questionnaires. Group differences were calculated
      using ANOVA (ANOVA/MANOVA). RESULTS: Treatment was well tolerated in both groups,
      although local and systemic side effects were more frequently reported in the
      bacillus Calmette-Guerin arm. Multivariate analyses showed no significant
      differences between the 2 groups in all quality of life dimensions. No
      significant changes over time in quality of life domains were detected for
      patients on bacillus Calmette-Guerin and gemcitabine except for physical
      functioning, which decreased significantly in both groups (p = 0.002). No
      significant differences were detected in terms of recurrence and progression
      between the 2 groups at 1-year followup. CONCLUSIONS: While a higher rate of side
      effects, albeit mild to moderate, was detected with 1/3 dose bacillus Calmette
      Guerin compared to gemcitabine, our study failed to show significant differences
      between the 2 drugs in terms of quality of life.

PMID- 23545102
TI  - Transcutaneous parasacral electrical neural stimulation in children with primary
      monosymptomatic enuresis: a prospective randomized clinical trial.
AB  - PURPOSE: Parasacral transcutaneous electrical neural stimulation is widely used
      to treat hyperactive bladder in children and adults. Its use in
      nonmonosymptomatic enuresis has demonstrated improvement in number of dry nights.
      We assessed the effectiveness of parasacral transcutaneous electrical neural
      stimulation in the treatment of monosymptomatic primary enuresis. MATERIALS AND
      METHODS: This prospective randomized clinical trial included 29 girls and 16 boys
      older than 6 years with primary monosymptomatic enuresis. Children were randomly
      divided into 2 groups consisting of controls, who were treated with behavioral
      therapy, and an experimental group, who were treated with behavioral therapy plus
      10 sessions of parasacral transcutaneous electrical neural stimulation. Neural
      stimulation was performed with the electrodes placed in the sacral region
      (S2/S3). Sessions always followed the same pattern, with duration of 20 minutes,
      frequency of 10 Hz, a generated pulse of 700 MUs and intensity determined by the
      sensitivity threshold of the child. Sessions were done 3 times weekly on
      alternate days. Patients in both groups were followed at 2-week intervals for the
      first month and then monthly for 6 consecutive months. RESULTS: Rate of wet
      nights was 77% in controls and 78.3% in the experimental group at onset of
      treatment (p = 0.82), and 49.5% and 31.2%, respectively, at the end of treatment
      (p = 0.02). Analyzing the average rate of improvement, there was a significantly
      greater increase in dry nights in the group undergoing neural stimulation (61.8%)
      compared to controls (37.3%, p = 0.0038). At the end of treatment percent
      improvement in children undergoing electrical stimulation had no relation to
      gender (p = 0.391) or age (p = 0.911). CONCLUSIONS: Treatment of primary
      monosymptomatic enuresis with 10 sessions of parasacral transcutaneous electrical
      neural stimulation plus behavioral therapy proved to be effective. However, no
      patient had complete resolution of symptoms.

PMID- 23545103
TI  - Effects of silodosin, a selective alpha1A-adrenoceptor antagonist, on bladder
      blood flow and bladder function in a rat model of atherosclerosis induced chronic
      bladder ischemia without bladder outlet obstruction.
AB  - PURPOSE: We investigated the effects of the selective alpha1A-adrenoceptor
      antagonist silodosin on bladder blood flow and bladder function in a rat model of
      atherosclerosis induced chronic bladder ischemia without bladder outlet
      obstruction. MATERIALS AND METHODS: The chronic bladder ischemia model was
      prepared by creating balloon endothelial injury of the bilateral iliac arteries
      in male rats. Using an osmotic pump, chronic bladder ischemia rats received
      silodosin subcutaneously at a rate of 0.1 or 0.3 mg/kg per day, or vehicle for 8
      weeks. All groups received a 2% cholesterol diet throughout the experiment. For
      each alpha1-adrenoceptor subtype mRNA expression in bladder microvessels was
      examined by in situ hybridization. Bladder blood flow was measured using a laser
      speckle blood flow imager. Malondialdehyde in bladder tissue and 8-hydroxy-2'
      deoxyguanosine in urine were measured as markers of oxidative stress. A metabolic
      cage study and cystometry were performed in conscious rats. RESULTS: The
      expression of all alpha1-adrenoceptor subtype mRNA was observed in rat bladder
      microvessels. Silodosin abrogated the decreased bladder blood flow in the empty
      bladder and during bladder distention that were evident in rats with chronic
      bladder ischemia. Levels of oxidative stress markers in these rats were
      significantly decreased by silodosin administration. Silodosin ameliorated
      bladder dysfunction in rats with chronic bladder ischemia in the metabolic cage
      study and on cystometry. CONCLUSIONS: Results suggest that in ischemic conditions
      alpha1-adrenoceptor antagonists such as silodosin may improve bladder function by
      restoring bladder blood flow.

PMID- 23545104
TI  - Preparation of 1,3-bis(allyloxy)benzene under a new multi-site phase-transfer
      catalyst combined with ultrasonication--a kinetic study.
AB  - In the present work, kinetics of synthesis of 1,3-bis(allyloxy)benzene was
      successfully carried out by O-allylation of resorcinol with allyl bromide using
      aqueous potassium hydroxide and catalyzed by a new multi-site phase-transfer
      catalyst viz., 1,3,5,7-tetrabenzylhexamethylenetetraammonium tetrachloride, MPTC
      under ultrasonic (40 kHz, 300 W) assisted organic solvent condition. The pseudo
      first-order kinetic equation was applied to describe the overall reaction. Under
      ultrasound irradiation (40 kHz, 300 W) in a batch reactor, it shows that the
      overall reaction rate can be greatly enhanced to seven fold faster with
      ultrasound irradiation than without ultrasound. The present study provides a
      method to synthesize ethers by ultrasound assisted liquid-liquid phase-transfer
      catalysis condition.

PMID- 23545106
TI  - Effects of ultrasound treatment in purple cactus pear (Opuntia ficus-indica)
      juice.
AB  - Cactus pear (Opuntia ficus-indica) fruit is a berry with a tasty pulp full of
      seeds that constitutes about 10-15% of the edible pulp. In Mexico, cactus pear is
      mainly consumed fresh, but also has the potential to be processed in other
      products such as juice. The objective of this study was to evaluate the effect of
      different ultrasound conditions at amplitude levels ranging (40% and 60% for 10,
      15, 25 min; 80% for 3, 5, 8, 10, 15 and 25 min) on the characteristics of purple
      cactus pear juice. The evaluated parameters were related with the quality
      (stability,  degrees Brix, pH), microbial growth, total phenolic compounds,
      ascorbic acid and antioxidant activity (ABTS, DPPH and % chelating activity) of
      purple cactus pear juices. The ultrasound treatment for time period of 15 and 25
      min significantly reduced the microbial count in 15 and 25 min, without affecting
      the juice quality and its antioxidant properties. Juice treated at 80% of
      amplitude level showed an increased of antioxidant compounds. Our results
      demonstrated that sonication is a suitable technique for cactus pear processing.
      This technology allows the achievement of juice safety and quality standards
      without compromising the retention of antioxidant compounds.

PMID- 23545105
TI  - Resourceful synthesis of pyrazolo[1,5-a]pyrimidines under ultrasound irradiation.
AB  - Pyrazolo[1,5-a]pyrimidines were synthesized via the ultrasonic sonochemical
      method using the cyclocondensation reaction of 4-alkoxy-1,1,1-trifluoro-3-alken-2
      ones [CF3C(O)CH=C(R)(OMe) - where R=Me, Bu, i-Bu, Ph, 4-Me-C6H4, 4-F-C6H4, 4-Cl
      C6H4, 4-Br-C6H4, naphth-2-yl and biphen-4-yl] - with 3-amino-5-methyl-1H-pyrazole
      in the presence of EtOH for 5 min. This methodology has several advantages, for
      example, it is a simple procedure, it has an easy work-up, mild conditions, short
      reaction times (5 min) and produces satisfactory yields (61-98%).

PMID- 23545108
TI  - Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase
      inhibitors.
AB  - A novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors
      were derived from a fragment-based approach using information from X-ray
      crystallographic analysis of NS5B-inhibitor complexes and iterative rounds of
      parallel synthesis. Structure-based drug design strategies led to the discovery
      of potent sub-micromolar inhibitors 11a-c and 12a-c from a weak-binding fragment
      like structure 1 as a starting point.

PMID- 23545107
TI  - Nucleotide competing reverse transcriptase inhibitors: discovery of a series of
      non-basic benzofurano[3,2-d]pyrimidin-2-one derived inhibitors.
AB  - A HTS screen led to the identification of a benzofurano[3,2-d]pyrimidin-2-one
      core structure which upon further optimization resulted in 1 as a potent HIV-1
      nucleotide competing reverse transcriptase inhibitor (NcRTI). Investigation of
      the SAR at N-1 allowed significant improvements in potency and when combined with
      the incorporation of heterocycles at C-8 resulted in potent analogues not
      requiring a basic amine to achieve antiviral activity. Additional modifications
      at N-1 resulted in 33 which demonstrated excellent antiviral potency and improved
      physicochemical properties.

PMID- 23545109
TI  - Virtual medicinal chemistry: in silico pre-docking functional group
      transformation for discovery of novel inhibitors of botulinum toxin serotype A
      light chain.
AB  - A novel method for applying high-throughput docking to challenging metalloenzyme
      targets is described. The method utilizes information-based virtual
      transformation of library carboxylates to hydroxamic acids prior to docking,
      followed by compound acquisition, one-pot (two steps) chemical synthesis and in
      vitro screening. In two experiments targeting the botulinum neurotoxin serotype A
      metalloprotease light chain, hit rates of 32% and 18% were observed.

PMID- 23545110
TI  - 1,8-Naphthalimide-Cu(II) ensemble based turn-on fluorescent probe for the
      detection of thiols in organic aqueous media.
AB  - A 1,8-naphthalimide-Cu(II) ensemble was rationally designed and synthesized as a
      new turn-on fluorescent probe utilizing the 'chemosensing ensemble' method for
      detections of thiols (Cys, Hcy and GSH) with high selectivity over other alpha
      amino acids at pH 7.4 in organic aqueous media (EtOH/HEPES, v/v=9:1). The
      recognition mechanism was attributed to the remove Cu(II) from the 1,8
      naphthalimide-Cu(II) ensemble by thiols and the release of flurescence of ligand
      1. Remarkable fluorescence enhancements were therefore observed in the sensing
      process of thiols by the 1,8-naphthalimide-Cu(II) ensemble. Furthermore, the 1,8
      naphthalimide-Cu(II) ensemble was successfully applied to the fluorescence
      imaging of thiols in CHO cells with high sensitivity and selectivity.

PMID- 23545111
TI  - Identification of PDZ ligands by docking-based virtual screening for the
      development of novel analgesic agents.
AB  - Disrupting the interaction between the PDZ protein, PSD-95, and its target
      ligands (such as the glutamate NMDA receptor or the serotonin 5-HT2A receptor)
      was found to reduce hyperalgesia in various models of neuropathic pain. Here, we
      set out to identify lead molecules which would interact with PSD-95, and hence,
      would potentially display analgesic activity. We describe the virtual screening
      of the Asinex and Cambridge databases which together contain almost one million
      molecules. Using three successive docking filters and visual inspection, we
      identified three structural classes of molecules and synthesized a potential lead
      compound from each class. The binding of the molecules with the PDZ domains of
      PSD-95 was assessed by (1)H-(15)N HSQC NMR experiments. The analgesic activity of
      the best ligand, quinoline 2, was evaluated in vivo in a model of neuropathic
      pain and showed promising results.

PMID- 23545112
TI  - Voice recognition and altered connectivity in schizophrenic patients with
      auditory hallucinations.
AB  - Auditory verbal hallucination (AVH) is a pathological hallmark of schizophrenia;
      however, their neural basis is unclear. Voice identity is an important
      phenomenological feature of AVHs. Certain voice identity recognition deficits are
      specific to schizophrenic patients with AVHs. We tested our hypothesis that among
      schizophrenia patients with hallucination, dysfunctional voice identity
      recognition is associated with poor functional integration in the neural networks
      involved in the evaluation of voice identity. Using functional magnetic resonance
      imaging (fMRI) during a voice recognition task, we examined the modulation of
      neural network connectivity in 26 schizophrenic patients with or without AVHs,
      and 13 healthy controls. Our results showed that the schizophrenic patients with
      AVHs had altered frontotemporal connectivity compared to the schizophrenic
      patients without AVHs and healthy controls. The latter two groups did not show
      any differences in functional connectivity. In addition, the strength of
      frontotemporal connectivity was correlated with the accuracy of voice
      recognition. These findings provide preliminary evidence that impaired functional
      integration may contribute to the faulty appraisal of voice identity in
      schizophrenic patients with AVHs.

PMID- 23545113
TI  - Cement augmentation of the proximal femoral nail antirotation for the treatment
      of osteoporotic pertrochanteric fractures--a biomechanical cadaver study.
AB  - INTRODUCTION: Proximal femoral fractures will gain increasing importance in the
      future due to the epidemiological development. Osteoporosis is often a limiting
      factor in the achievement of implant stability. New nailing systems offer the
      possibility of augmentation of the femoral neck component with cement. The aim of
      this study was to perform a biomechanical comparison of implant stability in
      osteoporotic pertrochanteric fractures using the proximal femoral nail
      antirotation (PFNA, Synthes GmbH, Umkirch, Germany) with cement augmented and non
      augmented blades. MATERIALS AND METHODS: Bone mineral density (BMD) was measured
      by dual-energy X-ray absorptiometry (DEXA) in six pairs of fresh-frozen human
      femurs. Standardised pertrochanteric fractures (AO31-A2.3) were treated with a
      PFNA. Cement augmentation was performed in six constructs. Axial loading was
      applied according to a single-leg-stance model using a hydraulic testing machine
      increasing to 1400N over 10,000 cycles. Biomechanical comparisons between the two
      groups that were comparable concerning BMD, tip-apex-distance and native
      stiffness were made with regard to postoperative stiffness, survived cycles, load
      to failure, failure mechanism and axial displacement. RESULTS: The stiffness of
      all stabilised femurs was significantly lower than for native specimens (native
      702.5+/-159.6N/mm vs. postoperative 275.4+/-53.8N/mm, p<0.001). Stiffness after
      instrumentation was significantly greater for the cement augmented group than for
      the non-augmented group (300.6+/-46.7N/mm vs. 250.3+/-51.6N/mm, respectively,
      p=0.001). Five of the twelve constructs survived cyclic testing. Statistically
      significant differences of the BMD were detected between survived and failed
      constructs (0.79+/-0.17g/cm(2) vs. 0.45+/-0.12g/cm(2), respectively, p=0.028).
      The failure loads for specimens surviving 10,000 cycles were 4611.9+/-2078.9N in
      the cement augmented group (n=3) and 4516.3N and 3253.5N in the non-augmented
      group (n=2). Postoperative stiffness was found to be a positive predictor of
      maximum force to failure (R(2)=0.83, p=0.02). CONCLUSIONS: The results of this
      biomechanical study show that cement augmentation of the PFNA increases the
      implant stability in osteoporotic pertrochanteric fractures. Further studies are
      necessary to evaluate this procedure in providing long term clinical results.

PMID- 23545114
TI  - Analysis of fatigue properties and failure mechanisms of Ti6Al4V in the very high
      cycle fatigue regime using ultrasonic technology and 3D laser scanning
      vibrometry.
AB  - Accelerated fatigue tests with Ti6Al4V were carried out using a 20kHz ultrasonic
      testing facility to investigate the cyclic deformation behavior in the Very High
      Cycle Fatigue (VHCF) regime in detail. Beside parameters like the ultrasonic
      generator power and the displacement of the specimen, a 3D laser scanning
      vibrometer was used to characterize the oscillation and fatigue behavior of the
      Ti-alloy. The course of the S-N(f) curve at the stress ratio R=-1 shows a
      significant decrease of the bearable stress amplitude and a change from surface
      to subsurface failures in the VHCF regime for more than 107 cycles. Microscopic
      investigations of the distribution of the alpha- and beta-phase of Ti6Al4V
      indicate that inhomogeneities in the phase distribution are reasons for the
      internal crack initiation. High resolution vibrometry was used to visualize the
      eigenmode of the designed VHCF-specimen at 20 kHz in the initial state and to
      indicate local changes in the eigenmodes as a result of progressing fatigue
      damage. Non-contact strain measurements were realized and used to determine the
      stress amplitude. The determined stress amplitudes were correlated with strain
      gauge measurements and finite element analysis.

PMID- 23545115
TI  - Modified lipoproteins as biomarkers of cardiovascular risk in diabetes mellitus.
AB  - Prevention of high incidence of cardiovascular disease in diabetes is one of the
      challenges of endocrinology. Validation of new biomarkers that may contribute to
      a better assessment of cardiovascular risk and help implement treatment
      strategies is one of the promising approaches in research on prevention and
      reduction of cardiovascular risk. Modification of low density lipoprotein (LDL)
      is a key element in development of atherosclerotic lesions. Several
      pathophysiological characteristics of diabetes are crucial for the LDL of these
      patients to have higher modification rates as compared to the healthy population.
      Diabetic dyslipidemia, hyperglycemia, and oxidative stress synergistically
      promote the occurrence of lipoperoxidation, glycosylation and glycoxidation
      processes, which will generate modified lipoproteins that stimulate development
      of atherosclerosis. This article reviews the role of different types of modified
      LDL in development of atherosclerosis in diabetes, as well as the possibility of
      using its quantification in cardiovascular risk prediction. 

PMID- 23545116
TI  - [Neurolymphomatosis as initial manifestation of recurrence in lymphoma].

PMID- 23545117
TI  - Genome wide array analysis indicates that an amyotrophic lateral sclerosis
      mutation of FUS causes an early increase of CAMK2N2 in vitro.
AB  - Mutations in the RNA binding protein FUS (fused in sarcoma) have been linked to a
      subset of familial amyotrophic lateral sclerosis (ALS) cases. The mutations are
      clustered in the C-terminal nuclear localization sequence (NLS). Various FUS
      mutants accumulate in the cytoplasm whereas wild-type (WT) FUS is mainly nuclear.
      Here we investigate the effect of one ALS causing mutant (FUS-DeltaNLS, also
      known as R495X) on pre-mRNA splicing and RNA expression using genome wide exon
      junction arrays. Using a non-neuronal stable cell line with inducible FUS
      expression, we detected early changes in RNA composition. In particular, mutant
      FUS-DeltaNLS increased calcium/calmodulin-dependent protein kinase II inhibitor 2
      (CAMK2N2) at both mRNA and protein levels, whereas WT-FUS had no effect.
      Chromatin immunoprecipitation experiments showed that FUS-DeltaNLS accumulated at
      the CAMK2N2 promoter region, whereas promoter occupation by WT-FUS remained
      constant. Given the loss of FUS-DeltaNLS in the nucleus through the mutation
      induced translocation, this increase of promoter occupancy is surprising. It
      indicates that, despite the obvious cytoplasmic accumulation, FUS-DeltaNLS can
      act through a nuclear gain of function mechanism.

PMID- 23545118
TI  - The contribution of goal specificity to goal achievement in collaborative goal
      setting for the management of asthma.
AB  - BACKGROUND: Goal setting was investigated as part of an implementation trial of
      an asthma management service (PAMS) conducted in 96 Australian community
      pharmacies. Patients and pharmacists identified asthma-related issues of concern
      to the patient and collaboratively set goals to address these. Although goal
      setting is commonly integrated into disease state management interventions, the
      nature of goals, and their contribution to goal attainment and health outcomes
      are not well understood. OBJECTIVES: To identify and describe: 1) goals set
      collaboratively between adult patients with asthma and their pharmacist, 2) goal
      specificity and goal achievement, and 3) describe the relationships between
      specificity, achievement, asthma control and asthma-related quality of life.
      METHODS: Measures of goal specificity, and goal achievement were developed and
      applied to patient data records. Goals set were thematically analyzed into goal
      domains. Proportions of goals set, goals achieved and their specificity were
      calculated. Correlational and regression analyses were undertaken to determine
      the relationships between goal specificity, goal achievement, asthma control and
      asthma-related quality of life. RESULTS: Data were drawn from 498 patient
      records. Findings showed that patients set a wide range and number of asthma
      related goals (N = 1787) and the majority (93%) were either achieved or being
      working toward by the end of the study. Goal achievement was positively
      associated with specific and moderately specific goals, but not non-specific
      goals. However, on closer inspection, an inconsistent pattern of relationships
      emerged as a function of goal domain. Findings also showed that goal setting was
      associated with end-of-study asthma control but not to asthma-related quality of
      life. CONCLUSIONS: Pharmacists can help patients to set achievable and specific
      asthma management goals, and these have the potential to directly impact health
      outcomes such as asthma control. Goal specificity appears to be an important
      feature in the achievement of goals, but other factors may also play a role.

PMID- 23545119
TI  - Fast oscillations during gasping and other non-eupneic respiratory behaviors:
      Clues to central pattern generation.
AB  - The mammalian nervous system exhibits fast synchronous oscillations, which are
      especially prominent in respiratory-related nerve discharges. In the phrenic
      nerve, they include high- (HFO), medium- (MFO), and low-frequency (LFO)
      oscillations. Because motoneurons firing at HFO-related frequencies had never
      been recorded, an epiphenomenological mechanism for their existence had been
      posited. We have recently recorded phrenic motoneurons firing at HFO-related
      frequencies in unanesthetized decerebrate rats and showed that they exhibit
      dynamic coherence with the phrenic nerve, validating synchronous motoneuronal
      discharge as a mechanism underlying the generation of HFO. In so doing, we have
      helped validate the conclusions of previous studies by us and other investigators
      who have used changes in fast respiratory oscillations to make inferences about
      central respiratory pattern generation. Here, we seek to review changes occurring
      in fast synchronous oscillations during non-eupneic respiratory behaviors, with
      special emphasis on gasping, and the inferences that can be drawn from these
      dynamics regarding respiratory pattern formation.

PMID- 23545120
TI  - The Changing landscape of health care delivery and the Heart Rhythm community.

PMID- 23545122
TI  - Personalizing the management of men with intermediate-risk prostate cancer.

PMID- 23545123
TI  - Facile Cu(I)-catalyzed oxidative coupling of anilines to azo compounds and
      hydrazines with diaziridinone under mild conditions.
AB  - A mild and highly efficient Cu(I)-catalyzed oxidative coupling of anilines is
      described. Various primary and secondary anilines can be efficiently coupled
      under mild conditions to the corresponding azo compounds and hydrazines in high
      yields. This method provides a direct and practical access to these compounds and
      is also amenable to gram scale with no special precautions to exclude air or
      moisture.

PMID- 23545124
TI  - Dating violence must be addressed in the public health forum.

PMID- 23545125
TI  - Imaging of thyroid carcinoma with CT and MRI: approaches to common scenarios.
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) can play an
      important role in preoperative and post-treatment assessment of thyroid
      malignancy. The radiologist should be aware of the pathological behavior of
      thyroid carcinoma, and the characteristic imaging appearance of the primary tumor
      and metastases. This review describes the approach to imaging thyroid cancer on
      CT and MRI for four common scenarios: detection of the incidental thyroid nodule,
      evaluation of thyroid metastases, presurgical imaging for invasive disease, and
      evaluation for recurrence in the post-treatment neck.

PMID- 23545126
TI  - Shift worked, quality of sleep, and elevated body mass index in pediatric nurses.
AB  - Using the Neuman Systems Model framework, the relationship between shift worked,
      quality of sleep, and body mass index (BMI) was explored in nurses working at
      least 8 hours per shift on units providing 24-hour care at a Magnet recognized,
      Midwestern free-standing pediatric hospital. Electronic surveys collected
      demographic data and the Pittsburgh Quality of Sleep Index (PSQI) measured sleep
      quality. Sleep quality was not significantly correlated to elevated BMI >30.
      Night shift participants' reported fairly bad to very bad sleep quality scores at
      higher rates than day shift participants. Study findings will inform nurses and
      organizations concerned with maintaining a healthy workforce.

PMID- 23545127
TI  - Parasite-induced and parasite development-dependent alteration of the swimming
      behavior of fish hosts.
AB  - Parasites with complex life cycles have the ability to change the behavior of
      their intermediate host in a way that increases their transmission rate to the
      next host. However, the level of behavioral changes can vary considerably,
      depending on the stage of parasite development and parasite intensity. To
      investigate the influence of such parameters, we evaluated the locomotory
      activity of the fish Poecilia vivipara prior to experimental infections, 7 days
      post-infection (dpi) and 14dpi with cercariae of the digenean Ascocotyle
      (Phagicola) pindoramensis. The locomotory activity was monitored using an image
      system, Videomex((r)), linked to with a video camera able to record the swimming
      behavior of the fishes. At the end of the experiments, fishes were dissected and
      all metacercariae from the gills and mesenteries, the specific sites utilized by
      A. (P.) pindoramensis, were recovered and counted. There was a significant
      decrease in the swimming behavior of fishes after 14dpi. Similarly, we found a
      significant correlation between the swimming behavior of the fishes and parasite
      intensity in both sites of infection. It is surmised that the decrease in
      locomotory activity of P. vivipara caused by A. (P.) pindoramensis can disturb
      its predator-prey relationship in natural environment.

PMID- 23545128
TI  - The role of traditional treatment on health care seeking by caregivers for sick
      children in Sierra Leone: results of a baseline survey.
AB  - In Sierra Leone, traditional treatment is at times used in lieu of seeking
      allopathic healthcare for major illnesses causing child death. This paper
      describes the nature of traditional treatment for diarrhea and fever (presumed
      malaria). Weighted analysis and multi-logistic regression was applied to a
      household cluster survey (n=5951) conducted in 4 districts in June 2010. Using
      structured questionnaires, heads of households, and caregivers of children under
      five years of age were interviewed about child morbidity and care seeking. A
      thematic analysis of qualitative data based on focus group discussions and in
      depth interviews with family members from twelve villages in these same four
      districts, was also done. Illness-specific herbal remedies were described by
      respondents. Among 1511 children with diarrhea, 31% used traditional treatment.
      Among 3851 children with fever, 22% used traditional treatment. Traditional
      treatment for diarrhea was associated with being from a tribe other than the
      Mende, using government recommended salt sugar solution, not having a vaccine
      card, having more than two illnesses, and not seeking any allopathic medical
      treatment for diarrhea. For fever, traditional treatment was associated with
      being a tribe other than the Mende, having more than two illnesses, not having a
      vaccine card, Muslim religion, and not seeking any allopathic medical treatment
      for fever. Qualitatively, respondents describe herbalists as trusted with
      remedies that are seen to be appropriate due to the perceived cause of illness
      and due to barriers to seeking care from government providers. The social
      determinants of traditional treatment use and the prominent role of herbalists in
      providing them need to be addressed to improve child survival in Sierra Leone.

PMID- 23545129
TI  - Reduction of mosquito biting-pressure: spatial repellents or mosquito traps? A
      field comparison of seven commercially available products in Israel.
AB  - The present study assessed the personal protection efficiency of seven
      commercially available mosquito control devices (MCD) under field conditions in
      Israel. Trials were performed in a high biting-pressure area inhabited by large
      populations of mosquito and biting midge species, using human volunteers as bait
      in landing catch experiments. Results show that under minimal air-movement, three
      spatial repellent based products (ThermaCELL((r)) Patio Lantern, OFF!((r))
      PowerPad lamp, and Terminix((r)) ALLCLEAR Tabletop Mosquito Repeller)
      significantly reduced the biting-pressure (t-test - P<0.01) when positioned at
      short distances from a volunteer (3, 7.5, and 10ft.), with the ThermaCELL unit
      being most effective (96.1, 89.9, and 76.66% reduction, respectively). No
      significant differences were seen between the three aforementioned devices at
      distances of 3 and 7.5ft., while at a distance of 10ft., only the ThermaCELL
      patio lantern repelled significantly more mosquitoes then the Terminix ALLCLEAR
      Tabletop Mosquito Repeller (t-test, P<0.05). In contrast, mosquito traps using
      attracting cues to bait mosquitoes (Dynatrap((r)), Vortex((r)) Electronic Insect
      Trap, Blue Rhino((r)) SV3100) either significantly increased or had no effect on
      the biting-pressure at short distances compared with the unprotected control.
      Trials conducted over large areas showed that only the Blue Rhino trap was able
      to significantly reduce the biting-pressure (40.1% reduction), but this was only
      when operating four units at the corners of an intermediate sized area.

PMID- 23545130
TI  - Fumigant toxicity of Citrus sinensis essential oil on Musca domestica L. adults
      in the absence and presence of a P450 inhibitor.
AB  - Essential oils (EOs) are potential tools for controlling Musca domestica L. In a
      fumigant assay, M. domestica adults treated with Citrus sinensis EO
      (LC50=3.9mg/dm(3)), with (4R)(+)-limonene (95.1%) being its main component, died
      within 15min or less. The terpenes absorbed by the flies and their metabolites,
      analyzed using SPME fiber, were (4R)(+)-limonene (LC50=6.2mg/dm(3)), alpha-pinene
      (LC50=11.5mg/dm(3)), beta-pinene (LC50=6.4mg/dm(3)), and two new components,
      carveol (LC50=1122mg/dm(3)) and carvone (LC50=19mg/dm(3)), in a proportion of 50,
      6.2, 12.5, 6.3 and 25%, respectively. Carveol and carvone were formed by
      oxidation of (4R)(+)-limonene mediated by cytochrome P450, as was suggested by a
      fumigation assay on flies previously treated with piperonyl butoxide, a P450
      inhibitor. In this experiment, an increase in the toxicity of the EO and (4R)(+)
      limonene was observed, as well as a lower production of carveol and carvone.

PMID- 23545131
TI  - New molecular identifiers for Simulium limbatum and Simulium incrustatum s.l. and
      the detection of genetic substructure with potential implications for
      onchocerciasis epidemiology in the Amazonia focus of Brazil.
AB  - The Amazonia onchocerciasis focus of southern Venezuela and northern Brazil is
      the larger of the two remaining Latin American onchocerciasis foci where disease
      transmission still occurs and is often regarded as the most challenging of all
      the Latin American foci to eliminate onchocerciasis. The site is home to a
      population of over 20,000 semi-nomadic, hunter-gatherer Yanomami people and is
      made-up of a mosaic of rainforest and savannah ecologies, which are influenced by
      the area's undulating terrain and rich geological diversity. At least six
      blackfly vectors have been implicated in onchocerciasis transmission in this
      focus; however, because of the difficulty in their routine identification the
      relative importance of each has been obscured. Simulium limbatum and Simulium
      incrustatum s.l. have both been recorded as vectors in the Amazonia focus, but
      they are difficult to discriminate morphologically and thus the ecological range
      of these species, and indeed the presence of S. limbatum in the Amazonia focus at
      all, have remained controversial. In the work described here, we report 15 S.
      incrustatum s.l. CO1 sequences and 27 S. limbatum sequences obtained from field
      caught adult female blackflies collected from forest and savannah localities,
      inside and just outside the Amazonia focus. Phylogenetic analysis with the
      sequences generated in this study, showed that both the S. limbatum and the S.
      incrustatum s.l. CO1 sequences obtained (even from specimens living in sympatry)
      all fell into discrete species-specific bootstrap-supported monophyletic groups
      and thus confirmed the utility of the CO1 gene for identifying both these species
      inside the Amazonia focus. As the S. limbatum-exclusive cluster included CO1
      sequences obtained from forest-caught and morphologically identified specimens
      these results provide the clearest evidence yet of the presence of S. limbatum
      inside the Amazonia focus. The question, however, of whether S. limbatum is
      actually a vector in the focus still remains unanswered as the data presented
      here also suggest that S. limbatum found in the savannahs adjacent to, but
      outside the Amazonia focus (and which represent the only S. limbatum population
      to be unambiguously incriminated as a host of Onchocerca volvulus), are
      genetically distinct from those living inside the focus. These findings highlight
      the need for a clearer picture of the vector taxonomy inside the Amazonia
      onchocerciasis focus.

PMID- 23545132
TI  - A review of epidural simulators: where are we today?
AB  - Thirty-one central neural blockade simulators have been implemented into clinical
      practice over the last thirty years either commercially or for research. This
      review aims to provide a detailed evaluation of why we need epidural and spinal
      simulators in the first instance and then draws comparisons between computer
      based and manikin-based simulators. This review covers thirty-one simulators in
      total; sixteen of which are solely epidural simulators, nine are for epidural
      plus spinal or lumbar puncture simulation, and six, which are solely lumbar
      puncture simulators. All hardware and software components of simulators are
      discussed, including actuators, sensors, graphics, haptics, and virtual reality
      based simulators. The purpose of this comparative review is to identify the
      direction for future epidural simulation by outlining necessary improvements to
      create the ideal epidural simulator. The weaknesses of existing simulators are
      discussed and their strengths identified so that these can be carried forward.
      This review aims to provide a foundation for the future creation of advanced
      simulators to enhance the training of epiduralists, enabling them to
      comprehensively practice epidural insertion in vitro before training on patients
      and ultimately reducing the potential risk of harm. 

PMID- 23545133
TI  - Nonparametric Bayesian methods for one-dimensional diffusion models.
AB  - In this paper we review recently developed methods for nonparametric Bayesian
      inference for one-dimensional diffusion models. We discuss different possible
      prior distributions, computational issues, and asymptotic results.

PMID- 23545134
TI  - Chronic dietary exposure to chlorpyrifos causes behavioral impairments, low
      activity of brain membrane-bound acetylcholinesterase, and increased brain
      acetylcholinesterase-R mRNA.
AB  - Chlorpyrifos (CPF) is an organophosphate (OP) insecticide that is metabolically
      activated to the highly toxic chlorpyrifos oxon. Dietary exposure is the main
      route of intoxication for non-occupational exposures. However, only limited
      behavioral effects of chronic dietary exposure have been investigated. Therefore,
      male Wistar rats were fed a dose of 5mg/kg/day of CPF for thirty-one weeks.
      Animals were evaluated in spatial learning and impulsivity tasks after 21 weeks
      of CPF dietary exposure and one week after exposure ended, respectively. In
      addition, the degree of inhibition of brain acetylcholinesterase (AChE) was
      evaluated for both the soluble and particulate forms of the enzyme, as well as
      AChE gene expression. Also, brain acylpeptide hydrolase (APH) was investigated as
      an alternative target for OP-mediated effects. All variables were evaluated at
      various time points in response to CPF diet and after exposure ended. Results
      from behavioral procedures suggest cognitive and emotional disorders. Moreover,
      low levels of activity representing membrane-bound oligomeric forms (tetramers)
      were also observed. In addition, increased brain AChE-R mRNA levels were detected
      after four weeks of CPF dietary exposure. However, no changes in levels of brain
      APH were observed among groups. In conclusion, our data point to a relationship
      between cognitive impairments and changes in AChE forms, specifically to a high
      inhibition of the particulate form and a modification of alternative splicing of
      mRNA during CPF dietary exposure.

PMID- 23545135
TI  - Mapping the Vif-A3G interaction using peptide arrays: a basis for anti-HIV lead
      peptides.
AB  - Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3G (A3G) is a
      cytidine deaminase that restricts retroviruses, endogenous retro-elements and DNA
      viruses. A3G plays a key role in the anti-HIV-1 innate cellular immunity. The HIV
      1 Vif protein counteracts A3G mainly by leading A3G towards the proteosomal
      machinery and by direct inhibition of its enzymatic activity. Both activities
      involve direct interaction between Vif and A3G. Disrupting the interaction
      between A3G and Vif may rescue A3G antiviral activity and inhibit HIV-1
      propagation. Here, mapping the interaction sites between A3G and Vif by peptide
      array screening revealed distinct regions in Vif important for A3G binding,
      including the N-terminal domain (NTD), C-terminal domain (CTD) and residues 83
      99. The Vif-binding sites in A3G included 12 different peptides that showed
      strong binding to either full-length Vif, Vif CTD or both. Sequence similarity
      was found between Vif-binding peptides from the A3G CTD and NTD. A3G peptides
      were synthesized and tested for their ability to counteract Vif action. A3G 211
      225 inhibited HIV-1 replication in cell culture and impaired Vif dependent A3G
      degradation. In vivo co-localization of full-length Vif with A3G 211-225 was
      demonstrated by use of FRET. This peptide has the potential to serve as an anti
      HIV-1 lead compound. Our results suggest a complex interaction between Vif and
      A3G that is mediated by discontinuous binding regions with different affinities.

PMID- 23545136
TI  - Synthesis and cytotoxic activity of metallic complexes of lawsone.
AB  - In the present study, a series of metallic complexes of the 1,4-naphthoquinone
      lawsone (2-6) were synthesized and evaluated for potential cytotoxicity in a
      mouse leukemic macrophagic RAW 264.7 cell line. Cell viability was determined by
      the MTT assay. Significant growth inhibition was observed for the copper complex
      (4) with an IC(50) value of 2.5 MUM. This compound was selected for further
      evaluation of cytotoxic activity on several human cancer cells including HT-29
      (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and
      HeLa, (human cervical adenocarcinoma cells). Significant cell viability decrease
      was also observed in HepG2 cells. The apoptotic potential of this complex was
      evaluated in these cells. Compound 4 induced apoptosis by a mechanism that
      involves the activation of caspases 3, 8 and 9 and modulation of apoptotic
      related proteins such as Bax, Bad, and p53. These results indicate that metal
      complexes of lawsone derivatives, in particular compound 4, might be used for the
      design of new antitumoral agents.

PMID- 23545137
TI  - Traceless Staudinger acetylation of azides in aqueous buffers.
AB  - In this paper, we demonstrate the applicability of water-soluble p
      dimethylaminoethyl substituted phosphinomethanethiol in acetyl transfer reactions
      by the traceless Staudinger ligation with unprotected epsilon-azido lysine
      containing peptides in aqueous buffer systems. Additionally, we present an
      improved synthesis pathway for the water-soluble phosphinothiol linkers requiring
      less steps in a comparable overall yield in comparison to previously published
      protocols.

PMID- 23545138
TI  - (3R,4S,5R,6R,7S)-3,4,5,7-Tetrahydroxyconidine, an azetidine analogue of 6,7
      diepicastanospermine and a conformationally constrained d-deoxyaltronojirimycin,
      from l-arabinose.
AB  - The synthesis from l-arabinose of an azetidine analogue of 6,7
      diepicastanospermine and its glycosidase inhibition profile are described. 

PMID- 23545140
TI  - Intention to stay of nurses in current posts in difficult-to-staff areas of
      Yemen, Jordan, Lebanon and Qatar: a cross-sectional study.
AB  - BACKGROUND: The nursing workforce shortages in difficult-to-staff areas have
      implications not only for quality of care but also for population health
      outcomes. An understanding of attrition and of retention is important to inform
      policies on the nursing workforce. OBJECTIVES: This paper draws on questionnaire
      survey data from nurses working in difficult-to-staff areas in four countries in
      the Eastern Mediterranean Region (Yemen, Jordan, Lebanon and Qatar). It aims to
      identify the specific and common factors associated with nurses' intention to
      stay in their current post for the coming 1-3 years in three countries with an
      internally trained nursing workforce and in a fourth where the workforce is
      externally recruited. METHODS: Nurses working in 'difficult to staff' areas in
      Yemen, Jordan, Lebanon and Qatar were surveyed. A conceptual model composed of 6
      dimensions based on that of the World Health Organization was constructed with
      'intent to stay' (Career Decisions) as the main outcome. Regression models were
      constructed for each of the dimensions in the conceptual model with 'intent to
      stay' as the dependent variable for each of the study countries. Subsequently, a
      collective model that combined Lebanon, Jordan and Yemen was constructed to
      identify common factors that are associated with intent to stay. RESULTS: Factors
      associated with intent to stay differed for study countries. Marriage was
      positively associated with intent to stay in Lebanon and Jordan whereas years of
      experience were positively significant for Lebanon and Yemen. Shorter commuting
      time was significantly associated with intent to stay in Jordan whereas a
      preference for village life was significant for Lebanon. Job satisfaction was
      significantly associated with intent to stay in all study countries. Nurses in
      Lebanon, Jordan and Qatar who indicated that they would choose nursing if they
      had the opportunity to choose a career all over again were significantly more
      likely to intend to stay in their current post. CONCLUSIONS: Studies of nurses
      working in these areas can help national policymakers and local nursing directors
      better manage the sparse nursing workforce in these localities and to provide
      them with appropriate incentives and support to encourage them to stay.

PMID- 23545141
TI  - Palliative care case management in primary care settings: a nationwide survey.
AB  - BACKGROUND: In case management an individual or small team is responsible for
      navigating the patient through complex care. Characteristics of case management
      within and throughout different target groups and settings vary widely. Case
      management is relatively new in palliative care. Insight into the content of care
      and organisational characteristics of case management in palliative care is
      needed. OBJECTIVES: To investigate how many case management initiatives for
      palliative care there are in the Netherlands for patients living at home; to
      describe the characteristics of these initiatives with regard to content and
      organisation of care. SETTING: Primary care. DESIGN AND PARTICIPANTS: A
      nationwide survey of all 50 coordinators of networks in palliative care in the
      Netherlands was conducted. Additional respondents were found through snowball
      sampling. We looked at 33 possible initiatives using interviews (n=33) and
      questionnaires (n=30). RESULTS: We identified 20 initiatives for case management.
      All stated that case management is supplemental to other care. In all initiatives
      the case managers are registered nurses and most possess higher vocational
      education and/or further training. All initiatives seek to identify the
      multidimensional care needs of the patients and the relatives and friends who
      care for them. Almost all provide information and support and refer patients who
      need care. Differences are found between the organisations offering the case
      management, their target groups, the names of the initiatives and whether direct
      patient care is provided by the case manager. CONCLUSIONS: In the Netherlands,
      case management in palliative care is new. Several models of delivery were
      identified. Research is needed to gain insight into the best way to deliver case
      management. By describing characteristics of case management in palliative care,
      an important first step is made in identifying effective elements of case
      management.

PMID- 23545139
TI  - Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC
      and 2011 ACCF/AHA/HRS recommendations): a report of the American College of
      Cardiology/American Heart Association Task Force on practice guidelines.

PMID- 23545142
TI  - Ancient invasion of an extinct gammaretrovirus in cetaceans.
AB  - Endogenous gammaretroviruses (EGVs) have been widely studied in terrestrial
      mammals but seldom so in marine species. A genomic mining of the bottlenose
      dolphin (Tursiops truncatus) genome revealed a new EGV, termed Tursiops truncatus
      endogenous retrovirus (TTEV), which is divergent from extant mammalian EGVs.
      Molecular clock dating estimated the invasion time of TTEV into the host genome
      to be approximately 10-19 million years ago (MYA), while a previously identified
      killer whale endogenous gammaretrovirus (KWERV) was estimated to have invaded the
      host genome approximately 3-5 MYA. Using a PCR-based technique, we then verified
      that similar endogenous viruses exist in nine cetacean genomes. Phylogenetic
      analysis revealed that these cetacean EGVs are highly divergent from their
      counterparts in other mammals, including KWERV from the killer whale. In sum, we
      conclude that there have been at least two invasion episodes of EGVs into
      cetaceans during their evolutionary history.

PMID- 23545143
TI  - An insight into the PB1F2 protein and its multifunctional role in enhancing the
      pathogenicity of the influenza A viruses.
AB  - PB1F2 is the 11th protein of the influenza A virus. The protein has variable
      sizes with truncations either at the C- or N-terminal ends. The most recent
      example being the 2009 pandemic H1N1 virus which codes for only 11 amino-acids of
      the C-terminus. A review of the reports since the discovery of PB1F2 in 2001
      suggests a multifunctional role for this protein that includes a proapoptotic
      function in immune cells and an ability to cause increased pathogenesis in animal
      models by dysregulating cytokines and inducing inflammation. It has also been
      suggested that PB1F2 regulates polymerase activity via co-localization with PB1
      and causes enhanced secondary bacterial pneumonia. This review primarily focuses
      on understanding the proapoptotic ability of PB1F2, its sub-cellular localization
      and the mechanism through which it brings about apoptosis. We believe there is
      much more to learn about PB1F2, as many of its proposed functions are strain,
      host or cell-line specific.

PMID- 23545144
TI  - DNA methyltransferases 1 and 3B are required for hepatitis C virus infection in
      cell culture.
AB  - DNA methyltransferases (DNMTs) are responsible for establishing and maintaining
      DNA methylation, which are dysregulated in hepatitis C virus (HCV)-associated
      hepatocellular carcinoma (HCC). In this report, using lentivirus-mediated shRNA
      interference technology, we identified DNMT1 and DNMT3B as host factors involved
      in HCV propagation. Our results demonstrated that down-regulation of DNMT1 or
      DNMT3B expression in Huh7.5.1 cells severely impaired cell culture-produced HCV
      (HCVcc) infection. Furthermore, knockdown of DNMT1 or DNMT3B did not affect HCV
      entry and internal ribosome entry site (IRES)-directed translation but did
      inhibit subgenomic replication. In contrast, knockdown of DNMT3A had no
      significant effect on HCV infection, entry, translation, or replication, which
      suggested that DNMT3A did not play a significant role in HCV life cycle.
      Moreover, we showed that DNMT inhibitors 5-Aza-C and 5-Aza-dC significantly
      suppressed HCVcc infection, viral RNA replication, and protein expression. These
      results suggest that DNMTs are critical for HCV replication and may represent
      potent targets for the treatment of HCV infection.

PMID- 23545145
TI  - Dermatomyositis-erythrodermia: clinical presentation not associated to
      malignancy. A case report.
AB  - The association of erythroderma and dermatomyositis is rare. In 6 reported cases
      found by searching Pubmed, half of them were associated with digestive tract
      neoplasms (stomach and liver). We report the case of a 69 years-old woman with
      bilateral proximal weakness, joint pain, photosensitivity, facial and heliotrope
      erythema lasting 18 months. One month prior to hospital admission she showed
      progressive dysphagia and a universal erythema and scaling that affected mucosa,
      palms and soles with an accompanying weight loss of 10 kg in 6 months. No
      malignancy was identified at any level despite an exhaustive search.

PMID- 23545146
TI  - Direct compression of chitosan: process and formulation factors to improve powder
      flow and tablet performance.
AB  - Chitosan is a polymer derived from chitin that is widely available at relatively
      low cost, but due to compression challenges it has limited application for the
      production of direct compression tablets. The aim of this study was to use
      certain process and formulation variables to improve manufacturing of tablets
      containing chitosan as bulking agent. Chitosan particle size and flow properties
      were determined, which included bulk density, tapped density, compressibility and
      moisture uptake. The effect of process variables (i.e. compression force, punch
      depth, percentage compaction in a novel double fill compression process) and
      formulation variables (i.e. type of glidant, citric acid, pectin, coating with
      Eudragit S(r)) on chitosan tablet performance (i.e. mass variation, tensile
      strength, dissolution) was investigated. Moisture content of the chitosan powder,
      particle size and the inclusion of glidants had a pronounced effect on its flow
      ability. Varying the percentage compaction during the first cycle of a double
      fill compression process produced chitosan tablets with more acceptable tensile
      strength and dissolution rate properties. The inclusion of citric acid and pectin
      into the formulation significantly decreased the dissolution rate of isoniazid
      from the tablets due to gel formation. Direct compression of chitosan powder into
      tablets can be significantly improved by the investigated process and formulation
      variables as well as applying a double fill compression process. 

PMID- 23545147
TI  - The times they're a-changing: effects of circadian desynchronization on
      physiology and disease.
AB  - Circadian rhythms are endogenous and need to be continuously entrained
      (synchronized) with the environment. Entrainment includes both coupling internal
      oscillators to external periodic changes as well as synchrony between the central
      clock and peripheral oscillators, which have been shown to exhibit different
      phases and resynchronization speed. Temporal desynchronization induces diverse
      physiological alterations that ultimately decrease quality of life and induces
      pathological situations. Indeed, there is a considerable amount of evidence
      regarding the deleterious effect of circadian dysfunction on overall health or on
      disease onset and progression, both in human studies and in animal models. In
      this review we discuss the general features of circadian entrainment and
      introduce diverse experimental models of desynchronization. In addition, we focus
      on metabolic, immune and cognitive alterations under situations of acute or
      chronic circadian desynchronization, as exemplified by jet-lag and shiftwork
      schedules. Moreover, such situations might lead to an enhanced susceptibility to
      diverse cancer types. Possible interventions (including light exposure, scheduled
      timing for meals and use of chronobiotics) are also discussed. 

PMID- 23545148
TI  - Non-HDL-cholesterol/HDL-cholesterol is a better predictor of metabolic syndrome
      and insulin resistance than apolipoprotein B/apolipoprotein A1.
AB  - BACKGROUND: The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has
      been reported to be associated with metabolic syndrome (MetS) and insulin
      resistance (IR). Non-HDL-C is regarded as a surrogate marker for apoB in routine
      clinical practice. However, it is unclear whether the ratio of non-HDL-C to HDL-C
      is an equal or a better predictor than the apoB/apoA1 ratio for the
      identification of MetS and IR. METHODS: We performed a retrospective study of
      41,821 Korean adults who participated in a routine health screening examination.
      Anthropometry, fasting glucose, fasting insulin, HOMA-IR, CRP, lipid profiles,
      apoB, and apoA1 were measured. RESULTS: To compare the predictive value for MetS
      between different lipid ratios, we analyzed the ROC curves of apoB/apoA1 and non
      HDL-C/HDL-C ratios. ROC analysis showed that the AUCs of non-HDL-C/HDL-C (0.75
      [95% CI=0.74-0.76] in men and 0.84 [95% CI=0.83-0.85] in women) were
      significantly higher than those of apoB/apoA1 (0.66 [95% CI=0.65-0.67] in men and
      0.77 [95% CI=0.76-0.78] in women). The non-HDL-C/HDL-C ratio also showed a
      significantly stronger association with HOMA-IR than the apoB/apoA1 ratio. The
      optimal cutoff value of the non-HDL-C/HDL-C ratio for detection of MetS in men
      was 3.39, with a sensitivity of 66.7% and a specificity of 71.8%, whereas the
      optimal ratio cutoff value in women was 2.89, with a sensitivity of 75.7% and a
      specificity of 78.1%. CONCLUSIONS: Our findings indicate that the non-HDL-C/HDL-C
      ratio is a better marker than the apoB/apoA1 ratio for identifying IR and MetS in
      Koreans.

PMID- 23545149
TI  - The human female heart incorporates glucose more efficiently than the male heart.
AB  - BACKGROUND: Oestrogen is known to play a cardioprotective role in cardiovascular
      diseases, as demonstrated in a number of animal studies. However, few human
      studies have investigated sex-based differences with regard to cardiac glucose
      uptake using (18)F-fluorodeoxyglucose-positron emission tomography/computed
      tomography (FDG-PET/CT). METHODS: Therefore, we evaluated healthy male and female
      subjects who underwent FDG-PET/CT examination to determine whether there was a
      sex-related difference in cardiac glucose uptake with age. RESULTS: In females,
      the prevalence of maximal FDG uptake (PET score 2) demonstrated a convex pattern
      with ageing, and it peaked at age 51-60 years in the females, gradually
      decreasing to a minimum at age >70 years. In contrast, the prevalence of maximal
      FDG uptake by age in males was a mirror image of that in females, i.e. it formed
      a concave pattern with a nadir at 61-70 years, followed by an increase in the
      prevalence. These findings suggest that female hearts depend more on glucose as
      an energy substrate as they age, however, efficient glucose uptake is attenuated
      with increasing age. In contrast, the male heart sustains its glucose uptake
      capacity at age >70 years. CONCLUSION: This characteristic sex-based difference
      in cardiac glucose uptake might be related to the female predominance of
      Takotsubo cardiomyopathy.

PMID- 23545150
TI  - Effect of inhaled iloprost on the exercise function of Fontan patients: a
      demonstration of concept.
AB  - BACKGROUND: Exercise capacity following Fontan surgery is often depressed. An
      inability to reduce pulmonary vascular resistance appropriately during exercise
      may contribute to this phenomenon. The aim of this study was to determine whether
      administration of iloprost, a selective pulmonary vasodilator, would improve
      exercise function after Fontan procedure. METHODS: Double-blind, randomized,
      placebo controlled, crossover trial. Patients performed two cardiopulmonary
      exercise tests (CPX) separated by <1 month. A single nebulizer treatment
      (iloprost or placebo) was administered before each CPX. RESULTS: 18 patients aged
      12-49 (median 17) years were recruited. Mild throat discomfort developed in 10/18
      patients during iloprost administration; all but 1 were able to complete
      treatment. No symptoms developed during placebo treatments (p<0.001). Two
      additional patients did not complete CPX: one with atrial flutter; another with
      developmental issues that precluded adequate CPX. In the 15 remaining subjects
      oxygen pulse (a surrogate for forward stroke volume) at peak exercise was higher
      following iloprost (median increase 1.2 ml/beat; p<0.001). Peak VO2 also rose
      (median increase 1.3 ml/kg/min; p<0.04). Nine patients had peak VO2 <30
      ml/kg/min; each of these patients had higher peak VO2 following iloprost. Only
      3/6 patients with peak VO2 >30 ml/kg/min had higher peak VO2 following iloprost
      (p<0.04). CONCLUSIONS: Iloprost improves the peak oxygen pulse and peak VO2 of
      patients with Fontan physiology and appears to be particularly beneficial among
      patients with impaired exercise function. Treatment is associated with minor side
      effects. These findings support the concept of pulmonary vasodilator therapy in
      Fontan patients with limited functional capacity.

PMID- 23545151
TI  - Characteristics of intracranial aneurysms associated with extracranial carotid
      artery disease in South Korea.
AB  - OBJECTIVE: Although it is hypothesized that inflammatory signals and/or
      hemodynamic stress resulting from carotid disease increase the risk of aneurysm
      formation and growth, a relationship between intracranial aneurysms and
      extracranial carotid artery disease (ECAD) has not been explored. Here, we
      examined the characteristics of intracranial aneurysms associated with ECAD.
      METHODS: A total of 606 consecutive patients with stenosis of 50% or more of the
      proximal internal carotid artery (pICA) were enrolled. Stenosis was identified by
      conventional angiography between January 2003 and December 2009. We determined
      the prevalence of intracranial aneurysms in this population. The characteristics
      of the aneurysms were analyzed according to the degree and laterality of
      stenosis. The changes in the aneurysms were tracked for the evaluation of
      stability. RESULTS: In 86 patients (14.2%), 120 aneurysms were detected in
      association with pICA stenosis. In this group, 97 were associated with unilateral
      pICA stenosis. The distribution of aneurysms was independent of the laterality of
      stenosis, but aneurysms were more prevalent in the contralateral side as the
      stenosis grade increased (P<0.001). All aneurysms with an imaging follow-up (28.9
      +/- 14.3 months) were stable, and the course was not affected by treatment of the
      carotid stenosis. In 23 aneurysms associated with bilateral pICA stenosis, there
      was only one case that increased in size during a 41-month period. CONCLUSION:
      Intracranial aneurysms were most likely associated with ECAD, but were evenly
      distributed irrespective of the laterality of the stenosis. The distribution was
      related to the severity of the contralateral pICA stenosis. The low incidence of
      aneurysm growth or rupture in patients with significant ECAD indicates that these
      aneurysms do not require immediate intervention more than other conditions.

PMID- 23545152
TI  - A synthetic oxygen carrier in fibrin matrices promotes sciatic nerve regeneration
      in rats.
AB  - Tissue-engineering nerve conduits have been studied for a long time in bridging
      large nerve defects. However, the low oxygen availability within the nerve
      conduits, which results in death of migratory Schwann cells (SC) or loss of the
      newly formed tissue's function, is still an obstacle for axonal regeneration.
      Thus, it was hypothesized that an oxygen-enriched conduit would enhance axonal
      regeneration and functional recovery in vivo. To address this issue,
      perfluorotributylamine (PFTBA) enriched fibrin hydrogel was prepared and injected
      into collagen-chitosan conduits. The conduit containing PFTBA-enriched fibrin
      hydrogel was then used to bridge a 12-mm sciatic nerve defect in rats. The
      control rats were bridged with collagen-chitosan conduits filled with fibrin
      matrices without PFTBA. It was found that axonal regeneration and functional
      recovery in the combined PFTBA group were significantly higher than those in the
      control group without PFTBA. Further investigations showed that the mRNA and
      protein levels of S-100, brain-derived neurotrophic factor and nerve growth
      factor were enhanced by PFTBA at 1 and 3weeks after surgery. However, the mRNA
      and protein levels of vascular endothelial growth factor were in a similar range
      between the combined PFTBA group and the control group without PFTBA. In
      addition, immunohistochemical results showed that the morphological appearances
      of regenerated nerve and survival of SC were enhanced by PFTBA at 4 and 12weeks
      after surgery. In conclusion, PFTBA-enriched nerve conduit is capable of
      enhancing axonal regeneration, which provides a new avenue for achieving better
      functional recovery in the treatment of nerve defect.

PMID- 23545153
TI  - Serum complement enhances the responses of genotoxin- and oxidative stress
      sensitive Escherichia coli bioreporters.
AB  - Bacterial bioreporters are limited in their abilities to detect large polar
      molecules due to their membrane selectivity. In this study, the activity of serum
      complement was used to bypass this undesired selectivity. Initially, the serum
      complement activity was assessed using the responses of a bacterial bioreporter
      harboring a recA::luxCDABE transcriptional fusion when exposed to the
      chemotherapy drug, mitomycin C (MMC). Using 50  degrees C-treated serum, the
      limit of detection for this bacterial sensor was lowered by nearly 450-fold, from
      31 MUg/L to 0.07 MUg/L MMC. Real-time quantitative PCR demonstrated that serum
      treated cultures responded more strongly to 100 MUg/L MMC, with 3.1-fold higher
      recA expression levels. Subsequent experiments with other bioreporter strains
      also found enhanced sensitivities and responses. Finally, combining each of the
      above findings, tests were performed to demonstrate the potential application of
      the recA::luxCDABE bioreporter within a lab-on-a-CD platform as a point-of-care
      diagnostic to measure chemotherapeutic drug concentrations within blood.

PMID- 23545154
TI  - Hepatic transarterial chemoembolization and retroperitoneal lymph node
      radiofrequency ablation in the multidisciplinary approach of an overt metastatic
      leiomyosarcoma.
AB  - Metastatic leiomyosarcoma has a dismal prognosis, and therapy mainly consists of
      palliative systemic chemotherapy. A selected subgroup of patients with limited
      metastatic disease may eventually derive benefit from more aggressive strategies,
      including resection of isolated metastasis. We report here the successful use of
      hepatic transarterial chemoembolization and retroperitoneal lymph node
      radiofrequency ablation in a patient with advanced leiomyosarcoma metastatic to
      the liver and retroperitoneum.

PMID- 23545155
TI  - Single-hidden-layer feed-forward quantum neural network based on Grover learning.
AB  - In this paper, a novel single-hidden-layer feed-forward quantum neural network
      model is proposed based on some concepts and principles in the quantum theory. By
      combining the quantum mechanism with the feed-forward neural network, we defined
      quantum hidden neurons and connected quantum weights, and used them as the
      fundamental information processing unit in a single-hidden-layer feed-forward
      neural network. The quantum neurons make a wide range of nonlinear functions
      serve as the activation functions in the hidden layer of the network, and the
      Grover searching algorithm outstands the optimal parameter setting iteratively
      and thus makes very efficient neural network learning possible. The quantum
      neuron and weights, along with a Grover searching algorithm based learning,
      result in a novel and efficient neural network characteristic of reduced network,
      high efficient training and prospect application in future. Some simulations are
      taken to investigate the performance of the proposed quantum network and the
      result show that it can achieve accurate learning. 

PMID- 23545156
TI  - Event-based 3D reconstruction from neuromorphic retinas.
AB  - This paper presents a novel N-ocular 3D reconstruction algorithm for event-based
      vision data from bio-inspired artificial retina sensors. Artificial retinas
      capture visual information asynchronously and encode it into streams of
      asynchronous spike-like pulse signals carrying information on, e.g., temporal
      contrast events in the scene. The precise time of the occurrence of these visual
      features are implicitly encoded in the spike timings. Due to the high temporal
      resolution of the asynchronous visual information acquisition, the output of
      these sensors is ideally suited for dynamic 3D reconstruction. The presented
      technique takes full benefit of the event-driven operation, i.e. events are
      processed individually at the moment they arrive. This strategy allows us to
      preserve the original dynamics of the scene, hence allowing for more robust 3D
      reconstructions. As opposed to existing techniques, this algorithm is based on
      geometric and time constraints alone, making it particularly simple to implement
      and largely linear. 

PMID- 23545157
TI  - G protein-coupled estrogen receptor is required for the neuritogenic mechanism of
      17beta-estradiol in developing hippocampal neurons.
AB  - Estradiol promotes neuritogenesis in developing hippocampal neurons by a
      mechanism involving the upregulation of neurogenin 3, a Notch-regulated
      transcription factor. In this study we have explored whether G-protein coupled
      estrogen receptor 1 (GPER) participates in this hormonal action. GPER agonists
      (17beta-estradiol, G1, ICI 182,780) increased neurogenin 3 expression and
      neuritogenesis in mouse primary hippocampal neurons and this effect was blocked
      by the GPER antagonist G15 and by a siRNA for GPER. In addition, GPER agonists
      increased Akt phosphorylation in ser473, which is indicative of the activation of
      phosphoinositide-3-kinase (PI3K). G15 or GPER silencing prevented the estrogenic
      induction of Akt phosphorylation. Furthermore, the PI3K inhibitor wortmannin
      prevented the effect of G1 and estradiol on neurogenin 3 expression and the
      effect of estradiol on neuritogenesis. These findings suggest that GPER
      participates in the control of hippocampal neuritogenesis by a mechanism
      involving the activation of PI3K signaling.

PMID- 23545158
TI  - Phenotype and steroidogenic potential of PDGFRalpha-positive rat neonatal
      peritubular cells.
AB  - Platelet-derived growth factor receptor alpha (PDGFRalpha)-positive peritubular
      cells (PTCs) are suggested to be putative stem Leydig cells. At present little is
      known about their phenotype and steroidogenic potential. We isolated highly
      purified PDGFRalpha-positive neonatal PTCs by magnetic cell sorting (MACS) from
      8dpp rat testes and characterized them in vitro. We have demonstrated that
      PDGFRalpha-positive PTCs have a mixed phenotype. They expressed PTC-specific
      genes (alphaSma, Myh11), pluripotency markers (Pou5f1, nestin, Lifr) and genes
      encoding steroidogenic enzymes. Treatment with the cAMP-analog (Bu)2cAMP for 7
      days upregulated steroidogenic enzyme gene expression and significantly increased
      their steroidogenic potential. The main end-point steroid was progesterone due to
      rapid inactivation of CYP17 and 17betaHSD. Long-term culturing of PDGFRalpha
      positive PTCs increased the expression of Myh11, and treatment with (Bu)2cAMP
      attenuated this process. All together, our findings support the hypothesis that
      neonatal PDGFRalpha-positive PTCs are steroidogenic competent progeny of stem
      Leydig cells (SLCs) which give rise to the adult Leydig cell lineage.

PMID- 23545159
TI  - Chromatin architecture defines the glucocorticoid response.
AB  - The glucocorticoid receptor (GR) functions to regulate a wide group of
      physiological processes through hormone inducible interaction with genomic loci
      and subsequent manipulation of the transcriptional output of target genes.
      Despite expression in a wide variety of tissues, the GR has diverse roles that
      are regulated tightly in a cell type specific manner. With the advent of whole
      genome approaches, the details of that diversity and the mechanisms regulating
      them are beginning to be elucidated. This review aims describe the recent
      advances detailing the role chromatin structure plays in dictating GR
      specificity. 

PMID- 23545161
TI  - Acetaminophen reduces lipopolysaccharide-induced fever by inhibiting
      cyclooxygenase-2.
AB  - Acetaminophen is one of the world's most commonly used drugs to treat fever and
      pain, yet its mechanism of action has remained unclear. Here we tested the
      hypothesis that acetaminophen blocks fever through inhibition of cyclooxygenase-2
      (Cox-2), by monitoring lipopolysaccharide induced fever in mice with genetic
      manipulations of enzymes in the prostaglandin cascade. We exploited the fact that
      lowered levels of a specific enzyme make the system more sensitive to any further
      inhibition of the same enzyme. Mice were immune challenged by an intraperitoneal
      injection of bacterial wall lipopolysaccharide and their body temperature
      recorded by telemetry. We found that mice heterozygous for Cox-2, but not for
      microsomal prostaglandin E synthase-1 (mPGES-1), displayed attenuated fever,
      indicating a rate limiting role of Cox-2. We then titrated a dose of
      acetaminophen that did not inhibit the lipopolysaccharide-induced fever in wild
      type mice. However, when the same dose of acetaminophen was given to Cox-2
      heterozygous mice, the febrile response to lipopolysaccharide was strongly
      attenuated, resulting in an almost normalized temperature curve, whereas no
      difference was seen between wild-type and heterozygous mPGES-1 mice. Furthermore,
      the fever to intracerebrally injected prostaglandin E2 was unaffected by
      acetaminophen treatment. These findings reveal that acetaminophen, similar to
      aspirin and other non-steroidal anti-inflammatory drugs, is antipyretic by
      inhibiting cyclooxygenase-2, and not by inhibiting mPGES-1 or signaling cascades
      downstream of prostaglandin E2.

PMID- 23545162
TI  - Scanning transmission electron microscopic tomography of cortical bone using Z
      contrast imaging.
AB  - Previously we presented (McNally et al., 2012) a model for the ultrastructure of
      bone showing that the mineral resides principally outside collagen fibrils in the
      form of 5 nm thick mineral structures hundreds of nanometers long oriented
      parallel to the fibrils. Here we use high-angle annular dark-field electron
      tomography in the scanning transmission electron microscope to confirm this model
      and further elucidate the composite structure. Views of a section cut parallel to
      the fibril axes show bundles of mineral structures extending parallel to the
      fibrils and encircling them. The mineral density inside the fibrils is too low to
      be visualized in these tomographic images. A section cut perpendicular to the
      fibril axes, shows quasi-circular walls composed of mineral structures, wrapping
      around apparently empty holes marking the sites of fibrils. These images confirm
      our original model that the majority of mineral in bone resides outside the
      collagen fibrils.

PMID- 23545160
TI  - Suppression of cytokine signaling: the SOCS perspective.
AB  - The discovery of the Suppressor of Cytokine Signaling (SOCS) family of proteins
      has resulted in a significant body of research dedicated to dissecting their
      biological functions and the molecular mechanisms by which they achieve potent
      and specific inhibition of cytokine and growth factor signaling. The Australian
      contribution to this field has been substantial, with the initial discovery of
      SOCS1 by Hilton, Starr and colleagues (discovered concurrently by two other
      groups) and the following work, providing a new perspective on the regulation of
      JAK/STAT signaling. In this review, we reflect on the critical discoveries that
      have lead to our current understanding of how SOCS proteins function and discuss
      what we see as important questions for future research. 

PMID- 23545163
TI  - Progesterone blunts vascular endothelial cell secretion of endothelin-1 in
      response to placental ischemia.
AB  - OBJECTIVE: Preeclampsia (PE) is associated with hypertension and elevated
      endothelin (ET-1), an indicator of endothelial cell activation and dysfunction.
      Reduction of uteroplacental perfusion (RUPP) in the pregnant rat model of PE is
      characterized by elevated mean arterial pressure, inflammatory cytokines, and
      activation of the ET-1 system. We aim to determine whether 17-alpha
      hydroxyprogesterone caproate (17-OHPC) or progesterone suppresses these pathways.
      STUDY DESIGN: Plasma progesterone was purified from normal pregnant (NP) and PE
      patients and measured via enzyme-linked immunosorbent assay. Human umbilical vein
      endothelial cells were exposed to the sera with or without progesterone added and
      ET-1 was measured. Pregnant rats underwent the RUPP procedure with or without
      intraperitoneal 17-OHPC. Mean arterial pressure was compared in RUPP vs NP rats.
      Human umbilical vein endothelial cells were exposed to NP or RUPP sera, with and
      without progesterone and ET-1 measured. RESULTS: Progesterone was significantly
      decreased in PE women compared with NP women. In response to human sera, ET-1 was
      elevated in PE women compared to NP women, and decreased with addition of
      progesterone. Mean arterial pressure was significantly elevated in RUPP vs NP
      rats but was attenuated by 17-OHPC. ET-1 secretion was stimulated significantly
      by RUPP compared to NP rat sera, but attenuated by progesterone. CONCLUSION:
      Circulating progesterone is significantly lower in PE women compared to controls.
      17-OHPC attenuates hypertension in response to placental ischemia in RUPP rats.
      Progesterone blunts vascular ET-1 stimulated at cellular level by sera from PE
      women or RUPP rats. Decreased circulating progesterone is associated with
      stimulation of ET-1. 17-OHPC supplementation blunts hypertension and progesterone
      blunts endothelial cell ET-1 secretion in response to placental ischemia.

PMID- 23545164
TI  - Cost-effectiveness of endometrial evaluation prior to morcellation in surgical
      procedures for prolapse.
AB  - OBJECTIVE: The objective of the study was to compare the cost-effectiveness of 3
      screening options for endometrial cancer in asymptomatic, postmenopausal women
      prior to undergoing morcellation in minimally invasive supracervical hysterectomy
      and minimally invasive sacral colpopexy for the treatment of pelvic organ
      prolapse. STUDY DESIGN: A decision tree model was constructed to compare no
      screening, endometrial biopsy, and transvaginal ultrasound for asymptomatic,
      postmenopausal women prior to surgery. Effectiveness was measured by life-years.
      The incremental cost-effectiveness ratio, defined as the difference in cost
      between 2 screening options divided by the difference in life-years between the 2
      options, was calculated in 2012 US dollars for endometrial biopsy and
      transvaginal ultrasound, in comparison with no screening. RESULTS: Using an
      endometrial cancer prevalence of 0.6% and a 40% risk of upstaging after
      morcellation, the expected per-patient cost was $8800, $9023, and $9112 over 5
      years for no screening, endometrial biopsy, and transvaginal ultrasound,
      respectively. The expected life-years saved compared with no screening were
      0.00108 for endometrial biopsy and 0.00105 for transvaginal ultrasound, ie, 0.39
      and 0.38 days, respectively. The estimated incremental cost-effectiveness ratio
      was $207,348 for endometrial biopsy and $298,038 for transvaginal ultrasound
      compared with no screening. A sensitivity analysis showed that the prevalence of
      endometrial cancer and the risk of endometrial cancer upstaging after
      morcellation had the greatest impact on the cost-effectiveness of screening.
      CONCLUSION: For asymptomatic, postmenopausal women, preoperative endometrial
      evaluation via endometrial biopsy or transvaginal ultrasound helps improve the
      preoperative detection of endometrial cancer, but universal screening is not cost
      effective.

PMID- 23545165
TI  - Antimicrobial PVK:SWNT nanocomposite coated membrane for water purification:
      performance and toxicity testing.
AB  - This study demonstrated that coated nitrocellulose membranes with a nanocomposite
      containing 97% (wt%) of polyvinyl-N-carbazole (PVK) and 3% (wt%) of single-walled
      carbon nanotubes (SWNTs) (97:3 wt% ratio PVK:SWNT) achieve similar or improved
      removal of bacteria when compared with 100% SWNTs coated membranes. Membranes
      coated with the nanocomposite exhibited significant antimicrobial activity toward
      Gram-positive and Gram-negative bacteria (~ 80-90%); and presented a virus
      removal efficiency of ~ 2.5 logs. Bacterial cell membrane damage was considered a
      possible mechanism of cellular inactivation since higher efflux of intracellular
      material (Deoxyribonucleic acid, DNA) was quantified in the filtrate of PVK-SWNT
      and SWNT membranes than in the filtrate of control membranes. To evaluate
      possible application of these membrane filters for drinking water treatment,
      toxicity of PVK-SWNT was tested against fibroblast cells. The results
      demonstrated that PVK-SWNT was non toxic to fibroblast cells as opposed to pure
      SWNT (100%). These results suggest that it is possible to synthesize
      antimicrobial nitrocellulose membranes coated with SWNT based nanocomposites for
      drinking water treatment. Furthermore, membrane filters coated with the
      nanocomposite PVK-SWNT (97:3 wt% ratio PVK:SWNT) will produce more suitable
      coated membranes for drinking water than pure SWNTs coated membranes (100%),
      since the reduced load of SWNT in the nanocomposite will reduce the use of costly
      and toxic SWNT nanomaterial on the membranes.

PMID- 23545166
TI  - PKC activation during training restores mushroom spine synapses and memory in the
      aged rat.
AB  - Protein kinase C (PKC) epsilon and alpha activation has been implicated in
      synaptogenesis. We used aged rats to test whether the PKCepsilon/alpha activator
      bryostatin and PKCepsilon-specific activator DCP-LA combined with spatial memory
      training could restore mushroom dendritic spinogenesis and synaptogenesis.
      Compared with young rats, aged, learning-impaired rats had lower memory
      retention; lower densities of mushroom spines and synapses in the apical
      dendrites of CA1 pyramidal neurons; fewer PKCepsilon-containing presynaptic
      axonal boutons; and lower activation and expression of two PKCepsilon/alpha
      substrates, the mRNA-stabilizing protein HuD and brain-derived neurotrophic
      factor (BDNF). PKC activator treatment combined with spatial memory training
      restored mushroom spines and mushroom spine synapses; rescued PKCepsilon/alpha
      expression and PKC/HuD/BDNF signaling; and normalized memory to the levels seen
      in young rats. These effects were produced by treatment with either bryostatin or
      the PKCepsilon-specific activator, DCP-LA. Bryostatin also reversed alterations
      in GABAergic inhibitory postsynaptic currents (IPSPs) in aged, learning-impaired
      rats. Thus, our results support the therapeutic potential of PKC activators when
      added to cognitive rehabilitation for inducing mushroom spine synaptogenesis and
      reversing memory decline associated with aging.

PMID- 23545167
TI  - HUH site-specific recombinases for targeted modification of the human genome.
AB  - Site-specific recombinases (SSRs) have been crucial in the development of
      mammalian transgenesis. For gene therapy purposes, this approach remains
      challenging, because, for example, SSR delivery is largely unresolved and SSR DNA
      substrates must pre-exist in target cells. In this review, we discuss the
      potential of His-hydrophobic-His (HUH) recombinases to overcome some of the
      limitations of conventional SSRs. Members of the HUH protein family cleave single
      stranded (ss)DNA, but can mediate site-specific integration with the aid of the
      host replication machinery. Adeno-associated virus (AAV) Rep remains the only
      known example to support site-specific integration in human cells, and AAV is an
      excellent gene delivery vector that can be targeted to specific cells and
      organelles. Bacterial protein TrwC catalyzes integration into human sequences and
      can be delivered to human cells covalently linked to DNA, offering attractive new
      features for targeted genome modification.

PMID- 23545168
TI  - Proteomic analysis of strawberry achenes reveals active synthesis and recycling
      of L-ascorbic acid.
AB  - Although the commonly named strawberry fruit (Fragaria*ananassa) is the sum of
      achenes and receptacles, the true fruit in the botanical sense is the achene.
      Here we report the protein changes occurring in the achene when developing from
      immature to mature stage. We have used 2-DE followed by image analysis, and
      protein identification by PMF combined with MS/MS, to investigate the protein
      variations associated to this transition. From a total of 331 spots analyzed, the
      corresponding 315 proteins have been identified. Differentially accumulated
      proteins between immature and mature achenes mostly reflect the physiological
      events associated to seed development and maturation, with only a few changes
      related to the development of the dry pericarp. We have focused our attention on
      vitamin C biosynthesis. Interestingly, GDP-mannose 3',5'-epimerase, a key enzyme
      in the l-ascorbate biosynthesis pathway, and ascorbate peroxidase, involved in l
      ascorbic acid oxidation, accumulate in immature achenes. The higher amount of
      these enzymes found in the green achene is coincident with a higher content of l
      ascorbate, and higher expression levels of these and other gene encoding enzymes
      of the l-ascorbic acid biosynthesis pathway. Altogether our results suggest an
      important role of l-ascorbic acid at the early developmental stage of the achene.
      BIOLOGICAL SIGNIFICANCE: In this manuscript we report the identification of the
      most abundant proteins in strawberry (F.*ananassa) achenes at early and late
      stages of development, thus providing a proteomic view of the events that occur
      during the development of this organ. Despite the importance of strawberry as a
      commercial fruit, the molecular changes governing its growth and ripening
      processes are largely unknown. The lack of information is even greater in the
      case of the achenes, which are the true fruit and play a critical role in the
      developmental process of the receptacle. Our original proteomic study reported
      here, restricted to the achenes, completes the previous transcriptomic (very
      limited) and metabolomic maps of this organ, adding clarity to the role of the
      achene in the global ripening process. The results obtained not only complement
      the previous "omics" studies significantly, but also open new key questions that
      deserve further research (role of hormones). We finally focus on the biosynthesis
      of l-ascorbic acid, which appears to be tightly regulated by some specific
      pathways, and whose content is important in the achene. The information provided
      here will be of interest not only for the groups studying strawberry, but also
      for many other groups interested in the fruit ripening process, as well as for
      groups studying the regulation of l-ascorbic acid content in different plant
      tissues.

PMID- 23545169
TI  - Differential proteome analysis of serum proteins associated with the development
      of type 2 diabetes mellitus in the KK-A(y) mouse model using the iTRAQ technique.
AB  - To identify candidate serum molecules associated with the progression of type 2
      diabetes mellitus (T2DM), we carried out differential proteomic analysis using
      the KK-A(y) mouse, an animal model of T2DM with obesity. We employed an iTRAQ
      based quantitative proteomic approach to analyze the proteomic changes in the
      sera collected from a pair of 4-week-old KK-A(y) versus C57BL/6 mice. Among the
      227 proteins identified, a total of 45 proteins were differentially expressed in
      KK-A(y) versus C57BL/6 mice. We comparatively analyzed a series of the sera
      collected at 4 and 12weeks of age from KK-A(y) and C57BL/6 mice for the target
      protein using multiple reaction monitoring analysis, and identified 8
      differentially expressed proteins between the sera of these mice at both time
      points. Among them, serine (or cysteine) peptidase inhibitor, clade A, member 3K
      (SERPINA3K) levels were elevated significantly in the sera of KK-A(y) mice
      compared to C57BL/6 mice. An in vitro assay revealed that the human homologue
      SERPINA3 increased the transendothelial permeability of retinal microvascular
      endothelial cells, which may be involved in the pathogenesis of diabetes and/or
      diabetic retinopathy. With the identified proteins, our proteomics study could
      provide valuable clues for a better understanding of the underlying mechanisms
      associated with T2DM. BIOLOGICAL SIGNIFICANCE: In this paper, we investigated the
      serum proteome of KK-A(y) mice in a pre-diabetic state compared to that of wild
      type controls in an attempt to uncover early diagnostic markers of diabetes that
      are maintained through a diabetic phenotype. We used iTRAQ-based two-dimensional
      LC-MS/MS serum profiling, and identified several differentially expressed
      proteins at the pre-diabetic stage. The differential expression was confirmed by
      multiple reaction monitoring assay, which is fast gaining ground as a sensitive,
      specific, and cost-effective methodology for relative quantification of the
      candidate proteins. Using these techniques, we have identified eight candidate
      proteins of interest including SERPINA3K, which may be important in the pathology
      of T2DM and/or diabetic retinopathy.

PMID- 23545170
TI  - Eosinophilic oesophagitis: from physiopathology to treatment.
AB  - Eosinophilic oesophagitis is a chronic inflammatory disease characterized by
      eosinophilic infiltration of the oesophageal mucosa. Food and aero-allergens are
      involved in its pathogenesis. Dysphagia and food impaction are the dominant
      symptoms in adult with eosinophilic oesophagitis. However, a wide range of
      symptoms has been noticed such as chest pain or gastro-oesophageal reflux disease
      like symptoms. Upper gastro-intestinal endoscopy and oesophageal biopsies are
      crucial for the diagnosis of eosinophilic oesophagitis. Endoscopy might be normal
      or reveal typical patterns such as rings, furrows, exudates, oedema, and
      stricture. Two to four biopsies should be performed both in the distal and in the
      proximal oesophagus, and 15 eosinophils per high power field within the
      oesophageal epithelium are the minimal threshold to diagnose eosinophilic
      oesophagitis. Allergy testing is recommended, although its impact to orient
      treatment remains to be demonstrated. Eosinophilic oesophagitis treatment
      includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors
      are the first-line therapy as some eosinophilic oesophagitis phenotypes respond
      well to proton pump inhibitors. Topical viscous corticosteroids or diet
      elimination are the treatment of choice. There is no clear evidence in the
      literature to prefer one to the other. Finally endoscopic dilation should be
      considered in case of persistent symptomatic stenosis despite medical therapy. 

PMID- 23545171
TI  - Quantifying tumour heterogeneity with CT.
AB  - Heterogeneity is a key feature of malignancy associated with adverse tumour
      biology. Quantifying heterogeneity could provide a useful non-invasive imaging
      biomarker. Heterogeneity on computed tomography (CT) can be quantified using
      texture analysis which extracts spatial information from CT images (unenhanced,
      contrast-enhanced and derived images such as CT perfusion) that may not be
      perceptible to the naked eye. The main components of texture analysis can be
      categorized into image transformation and quantification. Image transformation
      filters the conventional image into its basic components (spatial, frequency,
      etc.) to produce derived subimages. Texture quantification techniques include
      structural-, model- (fractal dimensions), statistical- and frequency-based
      methods. The underlying tumour biology that CT texture analysis may reflect
      includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging
      studies show that CT texture analysis has the potential to be a useful adjunct in
      clinical oncologic imaging, providing important information about tumour
      characterization, prognosis and treatment prediction and response.

PMID- 23545172
TI  - A thermostabilized magnetogenosensing assay for DNA sequence-specific detection
      and quantification of Vibrio cholerae.
AB  - Vibrio cholerae is a human pathogen that causes mild to severe diarrheal
      illnesses and has major public health significance. Herein, we present a
      thermostabilized electrochemical genosensing assay combining the use of magnetic
      beads as a biorecognition platform and gold nanoparticles as a hybridization tag
      for the detection and quantification of V. cholerae lolB gene single-stranded
      asymmetric PCR amplicons as an alternative to the time-consuming classical
      isolation method. This thermostabilized, pre-mixed, pre-aliquoted and ready-to
      use magnetogenosensing assay simplified the procedures and permitted the reaction
      to be conducted at room temperature. The asymmetric PCR amplicons were hybridized
      to a magnetic bead-functionalized capture probe and a fluorescein-labeled
      detection probe followed by tagging with gold nanoparticles. Electrochemical
      detection of the chemically dissolved gold nanoparticles was performed using the
      differential pulse anodic stripping voltammetry method. The real-time stability
      evaluation of thermostabilized assay was found to be stable for at least 180 days
      at room temperature (25-30 degrees C). The analytical specificity of the assay
      was 100%, while its analytical sensitivity was linearly related to different
      concentrations of 200-mer synthetic target, purified genomic DNA, and bacterial
      culture with a limit of detection (LoD) of 3.9nM, 5pg/ul, and 10(3)CFU/ml,
      respectively. The clinical applicability of the assay was successfully validated
      using spiked stool samples with an average current signal-to-cut-off ratio of
      10.8. Overall, the precision of the assay via relative standard deviation was
      <10%, demonstrating its reliability and accuracy.

PMID- 23545173
TI  - Photoelectrochemical sensing for hydroquinone based on porphyrin-functionalized
      Au nanoparticles on graphene.
AB  - A novel light "on-off" photoelectrochemical sensing for the sensitive
      determination of hydroquinone was developed based on the porphyrin-functionalized
      Au nanoparticles on graphene (porphyrin/AuNPs/graphene). Gold nanoparticles
      (AuNPs) were firstly modified onto graphene sheets using NaBH4 as reductant and
      the porphyrin/AuNPs/graphene nanocomposites were then synthesized by self
      assembly decoration of sulfhydryl porphyrin on AuNPs modified graphene sheets by
      S-Au bond. The porphyrin/AuNPs/graphene nanocomposites were characterized by
      transmission electron microscopy, X-ray photoelectron, and ultraviolet-visible
      absorption spectroscopies. The nanocomposites showed good dispersion in water and
      on indium tin oxide (ITO) surface. The resulting porphyrin/AuNPs/graphene
      modified ITO electrode showed good photoelectrochemical behavior toward the
      oxidation of hydroquinone (HQ) at 0V under white light illumination. The proposed
      photoelectrochemical method could detect hydroquinone with a wide linear response
      ranging from 20 to 240nM (R=0.9914). The detection limit was 4.6nM for HQ
      (S/N=3). Thus, the nanocomposites would be expected to be a novel photoactive
      material for photoelectrochemical biosensing.

PMID- 23545174
TI  - Microbial fuel cell type biosensor for specific volatile fatty acids using
      acclimated bacterial communities.
AB  - Volatile fatty acid (VFA) concentration is one of the most important parameters
      for monitoring bio-processes such as anaerobic digestion and microbial fuel
      cells. In this study the correlation between VFA concentration and
      current/voltage responses and electrochemical properties by using the MFC
      technology was evaluated. The discrimination between different species of VFA by
      using two methods i.e., coulombic efficiency and cyclic voltammetry was
      investigated. Columbic efficiency gave a slow response of greater than 20h,
      particularly at concentration levels of 20mgl(-1). By using cyclic voltammetry to
      measure the oxidation peak at a consistent scan rate showed linear correlation to
      VFA concentration and peak current produced, up to <40mgl(-1)) in a rapid
      response time of 1-2min. The results presented showed good correlations between
      the individual VFA species concentration and charge, and also current generated.
      A MFC based biosensor array was produced capable of measuring individual acetate,
      propionate and butyrate concentrations with sensitivity down to 5mgl(-1) and up
      to 40mgl(-1).

PMID- 23545175
TI  - Optical sensing of urinary melatonin with molecularly imprinted poly(ethylene-co
      vinyl alcohol) coated zinc oxide nanorod arrays.
AB  - In this work, aligned zinc oxide (ZnO) nanorods were selectively hydrothermally
      grown on acetate-seeded spots on a gold substrate; the nanorods had an average
      length and diameter of 1.7MUm and 240nm, respectively. Melatonin was imprinted
      into poly(ethylene-co-vinyl alcohol), EVAL, which was coated onto ZnO nanorod
      arrays. The ZnO nanorods not only increased the surface area for sensing target
      molecules, but also constituted an optical sensing element, as the ZnO
      fluorescence decreases when targets bind to the imprinted EVAL film; the
      fluorescence decrease, as a function of melatonin concentration, is well fit by a
      Langmuir adsorption isotherm. Poly(ethylene-co-vinyl alcohol) with 44mol%
      ethylene showed the best imprinting effectiveness (ratio of the fluorescence
      decrease on binding melatonin to imprinted vs. non-imprinted EVAL-coated ZnO
      nanorod arrays) among the several compositions studied. In real urine analysis,
      the MIP films responded linearly to added (exogenous) melatonin, even in the
      presence of many possible interfering compounds in urine. This demonstrates the
      feasibility of using these MIPs as part of a total urinalysis MIP system.

PMID- 23545176
TI  - Hierarchical segmentation-assisted multimodal registration for MR brain images.
AB  - Information theory-based metric such as mutual information (MI) is widely used as
      similarity measurement for multimodal registration. Nevertheless, this metric may
      lead to matching ambiguity for non-rigid registration. Moreover, maximization of
      MI alone does not necessarily produce an optimal solution. In this paper, we
      propose a segmentation-assisted similarity metric based on point-wise mutual
      information (PMI). This similarity metric, termed SPMI, enhances the registration
      accuracy by considering tissue classification probabilities as prior information,
      which is generated from an expectation maximization (EM) algorithm. Diffeomorphic
      demons is then adopted as the registration model and is optimized in a
      hierarchical framework (H-SPMI) based on different levels of anatomical structure
      as prior knowledge. The proposed method is evaluated using Brainweb synthetic
      data and clinical fMRI images. Both qualitative and quantitative assessment were
      performed as well as a sensitivity analysis to the segmentation error. Compared
      to the pure intensity-based approaches which only maximize mutual information, we
      show that the proposed algorithm provides significantly better accuracy on both
      synthetic and clinical data.

PMID- 23545177
TI  - SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal
      transition via regulation of WNT/beta-catenin signal network.
AB  - SOX2 was reported to promote metastasis in various tumor tissues; however the
      underlying mechanisms remain elusive. Here, we disclosed that SOX2 improves
      metastasis of breast and prostate cancer cells by promoting epithelial-to
      mesenchymal transition (EMT) through WNT/beta-catenin, but not TGF-beta or Snail1
      signaling. Dual luciferase assay and chromatin immunoprecipitation revealed
      activation and binding of SOX2 on promoter region of beta-catenin. In addition,
      SOX2 affects the protein expression levels of DKK3, DVL1 and DVL3, which are
      regulators or downstream molecules of WNT signaling. Taken together, our findings
      demonstrated beta-catenin as one of vital downstream molecules that mediate the
      EMT induced by SOX2. 

PMID- 23545178
TI  - Quercitrin protects skin from UVB-induced oxidative damage.
AB  - Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to
      skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed
      that the skin damage induced by UV irradiation is a consequence of generation of
      reactive oxygen species (ROS). Recently, there is an increased interest in the
      use of natural products as chemopreventive agents for non-melanoma skin cancer
      (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin,
      glycosylated form of quercetin, is the most common flavonoid in nature with
      antioxidant properties. The present study investigated the possible beneficial
      effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in
      vitro and in vivo. Our results showed that quercitrin decreased ROS generation
      induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression
      and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes,
      leading to reductions of oxidative DNA damage and apoptosis and protection of the
      skin from inflammation caused by UVB exposure. The present study demonstrated
      that quercitrin functions as an antioxidant against UVB irradiation-induced
      oxidative damage to skin.

PMID- 23545179
TI  - Bisphenol A differentially activates protein kinase C isoforms in murine
      placental tissue.
AB  - Bisphenol A is utilized to make polycarbonate plastics and is an environmental
      pollutant. Recent research has indicated that it is an endocrine disruptor and
      may interfere with reproductive processes. Our lab has previously shown that
      bisphenol A could regulate corticotrophin releasing hormone and aromatase in
      cultured placental cells. In the present study, the effect of bisphenol A on
      these two genes in the placenta was investigated in mice. Pregnant ICR mice were
      gavaged with bisphenol A at 2, 20 and 200mg/kg body weight/day from E13 to E16
      and were euthanized at E17. Compared to the control mice, increased plasma
      estrogen and corticotrophin releasing hormone were observed in bisphenol A
      treated mice. Messenger RNA quantification indicated that placental crh but not
      cyp19 was induced in mice treated with bisphenol A. Tracking the related
      signaling pathway, we found that protein kinase C zeta/lambda and delta were
      activated in the placentas of bisphenol A-treated mice. As the gene promoter of
      crh contains CRE and the half site of ERE, either phospho-PKC or estrogen could
      stimulate the gene transactivation. These results indicate that bisphenol A might
      increase plasma concentrations of estradiol, testosterone, corticotrophin
      releasing hormone and placental phospho-PKC zeta/lambda and delta in mice.
      Ultimately, the incidence of premature birth in these mice could increase.

PMID- 23545180
TI  - Protective effects of the compounds isolated from the seed of Psoralea
      corylifolia on oxidative stress-induced retinal damage.
AB  - The mechanism underlying glaucoma remains controversial, but apoptosis caused by
      increased levels of reactive oxygen species (ROS) is thought to play a role in
      its pathogenesis. We investigated the effects of compounds isolated from Psoralea
      corylifolia on oxidative stress-induced cell death in vitro and in vivo.
      Transformed retinal ganglion cells (RGC-5) were treated with l-buthione-(S,R)
      sulfoximine (BSO) and glutamate in the presence or with pre-treatment with
      compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell
      death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the
      oxidative stress-induced decrease of mitochondrial membrane potential (MMP,
      DeltaPsim). Furthermore, while intracellular Ca(2+) was high in RGC-5 cells after
      exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo
      study, in which rat retinal damage was induced by intravitreal injection of N
      methyl-d-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and
      release of cytochrome c, and inhibited up-regulation of cleaved caspase-3,
      cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells
      (RGCs) 7days after optic nerve crush (ONC) in mice was significantly decreased;
      however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated
      ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved
      caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited
      translocation of mitochondrial AIF into the nuclear fraction and release of
      mitochondrial cytochrome c into the cytosol. These results demonstrate that
      bakuchiol isolated from P. corylifolia has protective effects against oxidative
      stress-induced retinal damage, and may be considered as an agent for treating or
      preventing retinal degeneration.

PMID- 23545181
TI  - Soil microbial communities respond differently to three chemically defined
      polyphenols.
AB  - High molecular weight polyphenols (e.g. tannins) that enter the soil may affect
      microbial populations, by serving as substrates for microbial respiration or by
      selecting for certain microbes. In this study we examined how three phenolic
      compounds that represent some environmentally widespread tannins or their
      constituent functional groups were respired by soil microorganisms and how the
      compounds affected the abundance and diversity of soil bacteria and archaea,
      including ammonia oxidizers. An acidic, silt loam soil from a pine forest was
      incubated for two weeks with the monomeric phenol methyl gallate, the small
      polyphenol epigallocatechin gallate, or the large polyphenol oenothein B.
      Respiration of the polyphenols during the incubation was measured using the
      MicrorespTM system. After incubation, metabolic diversity was determined by
      community level physiological profiling (CLPP), and genetic diversity was
      determined using denaturing gradient gel electrophoresis (DGGE) analysis on DNA
      extracted from the soil samples. Total microbial populations and ammonia
      oxidizing populations were measured using real time quantitative polymerase chain
      reaction (qPCR). Methyl gallate was respired more efficiently than the higher
      molecular weight tannins but not as efficiently as glucose. Methyl gallate and
      epigallocatechin gallate selected for genetically or physiologically unique
      populations compared to glucose. None of the polyphenols supported microbial
      growth, and none of the polyphenols affected ammonia-oxidizing bacterial
      populations or ammonia-oxidizing archaea. Additional studies using both a wider
      range of polyphenols and a wider range of soils and environments are needed to
      elucidate the role of polyphenols in determining soil microbiological diversity. 

PMID- 23545182
TI  - Reduced adiponectin receptor signalling accelerates atherosclerosis and may
      worsen the outcome in type 2 diabetes mellitus - another one of those missing
      links?

PMID- 23545183
TI  - High PLTP activity is associated with depressed left ventricular systolic
      function.
AB  - Phospholipid transfer protein (PLTP) modulates lipoprotein metabolism and plays
      an important role in inflammation and oxidative stress. High PLTP activity is
      associated with atherosclerosis and its risk factors, which also predispose to
      left ventricular systolic (LV) dysfunction and/or congestive heart failure.
      However there are few data linking PLTP activity directly to LV function.
      According, we sought to determine the relation between PLTP activity and LV
      ejection fraction (EF) in a Chinese cohort of 732 patients referred for coronary
      angiography. Weak but significant correlations of PLTP activity levels were found
      with age (r = -0.09, p = 0.017), male gender (r = 0.09, p = 0.019), diabetes (r =
      0.08, p = 0.036), TG (r = 0.11, p = 0.003), HDL-C (r = -0.18, p = <0.001), apo A
      (-0.30, p < 0.001) apo B (r = 0.20, p < 0.001), fibrinogen (r = 0.32, p < 0.001)
      and LVEF (r = -0.12, p = 0.003). Median PLTP activity levels were higher among
      patients with reduced than in normal LV systolic function (LVEF <50%) [26.7
      pmol/microl/h (IQR 20.2, 38.6) vs. 19.9 pmol/microl/h (IQR 12.2, 31.0), p <
      0.001]. There was a step-wise increase in median PLTP levels in patients with
      normal, mild, and moderate-severe degrees of LV dysfunction (19.9 pmol/microl/h
      vs. 25.1 pmol/microl/h vs. 34.7 pmol/microl/h, p < 0.001). Median PLTP activity
      levels were higher among patients with unstable rather than stable AP and non-CHD
      patients (25.9 pmol/microl/h vs 20.2 vs 21.9, p = 0.012). On multivariate
      analyzes, higher median PLTP activity levels were associated with depressed LV
      systolic function as a dichotomous variable and with lower LVEF as a continuous
      variable. In conclusion, higher PLTP activity is associated with depressed LV
      systolic function in a dose-dependent manner independent of coronary heart
      disease as well as to unstable CHD.

PMID- 23545184
TI  - Human exceptionalism.
AB  - How the unique capacities of human cognition arose in evolution is a question of
      enduring interest. The difficulty of finding the best allometric and
      developmental frame for brain evolution and growth, however, leads researchers to
      routinely identify predictable features of the human brain as exceptional.

PMID- 23545185
TI  - Falsely increased HCG in patients with high leukocyte counts.

PMID- 23545186
TI  - Standardized quantitative assessment of BCR-ABL1 transcripts on an international
      scale.

PMID- 23545187
TI  - Fate of (14)C-organic pollutant residues in composted sludge after application to
      soil.
AB  - Organic micropollutants may be present in biosolids, leading to soil
      contamination when they are recycled in agriculture. A sludge spiked with (14)C
      labelled glyphosate (GLY), sodium linear dodecylbenzene sulphonate (LAS),
      fluoranthene (FLT) or 4-n-nonylphenol (NP) was composted with green waste and the
      fate of the (14)C-micropollutant residues remaining after composting was assessed
      after the compost application to the soil. (14)C-residues were mineralised in the
      soil and represented after 140d 20-32% of the initial activity for LAS, 16-25%
      for GLY, 6-9% for FLT and 4-7% for NP. The (14)C-residues at the end of
      composting that could not be extracted with methanol or ammonia were minimally
      remobilised or even increased for FLT. After 140d, non-extractable residues
      represented 38-52% of all of the (14)C-residues remaining in the soil for FLT, 50
      67% for GLY, 91-92% for NP and 94-97% for LAS and in most cases, less than 1% of
      the (14)C-residues were water soluble, suggesting a low direct availability for
      leaching and microbial or plant assimilation. FLT was identified as the main
      compound among the methanol-extractable (14)C-residues that may be potentially
      available. The fate of the (14)C-organic pollutant residues in composts after
      application to soil could be assessed through a sequential chemical extraction
      scheme and depended on the chemical nature of the pollutant. 

PMID- 23545188
TI  - Phosphate removal ability of biochar/MgAl-LDH ultra-fine composites prepared by
      liquid-phase deposition.
AB  - Morphological structures and adsorption properties of biochar/MgAl-LDH ultra-fine
      composites prepared by liquid-phase deposition have been determined in
      laboratory. X-ray diffraction (XRD), scanning electron microscopy (SEM), energy
      dispersive X-ray analysis (EDS), and Fourier transform infrared (FTIR) were used
      to characterize the biochar based ultra-composites. The XRD and FTIR data
      indicated that the biochar/MgAl-LDHs ultra-fine composites can successfully be
      obtained by liquid-phase deposition. The SEM images showed the dispersion of
      colloidal and nanosized LDH flakes on the carbon surfaces within the biochar
      matrix. The thickness and size of single LDH platelet are 20-40 nm and 100-300
      nm. Batch sorption experiments were also conducted and the results indicated that
      the biochar/MgAl-LDHs ultra-fine composites is an effective sorbent for the
      removal of phosphate from aqueous solutions.

PMID- 23545189
TI  - Dissipation kinetics of trifloxystrobin and tebuconazole on apple (Malus
      domestica) and soil--a multi location study from north western Himalayan region.
AB  - A new combinational fungicide formulation trifloxystrobin 25%+tebuconazole 50%
      (Nativo 75WG), introduced as a part of resistance management strategy, was
      studied for dissipation behaviour on apple fruits. Nativo 75WG was sprayed twice
      at the rate of 400 g and 800 g a.i. ha(-1) equal to trifloxystrobin application
      rate of 100 and 200 g a.i. ha(-1) and tebuconazole at application rate of 200 and
      400 g a.i. ha(-1) at four different locations in the Northwest Himalayan region
      of India. The fruit samples collected at 10d interval and soil samples taken at
      harvest time were analyzed after second spray. The residual concentrations of
      trifloxystrobin, its acid metabolite CGA 321113 and tebuconazole were measured.
      Residues of both fungicides were determined by using gas chromatograph, Agilent
      6890N having electron capture detector. The mean initial deposits of
      trifloxystrobin at four locations were found to be in the range of 0.333-0.387 mg
      kg(-1) and 0.512-0.714 mg kg(-1) at the application rate of 100 and 200 g a.i.
      ha(-1), and half-life were found between 19.38-24.93 d and 19.84-28.86 d at the
      respective doses. The Sigma-trifloxystrobin and tebuconazole residues were below
      determination limit in 40 d apple fruits and soil samples. Initial deposits of
      trifloxystrobin and tebuconazole were below their Codex MRLs at the respective
      single doses. The half life value of the tebuconazole deposits ranged between
      19.38-25.99 d and 19.84-28.86 d at the respective single and double dose. The
      study thus suggests 1d pre harvest interval for safe consumption of apple fruit
      after the application of Nativo 75 WG at single dose.

PMID- 23545190
TI  - Can rainwater induce Fenton-driven degradation of herbicides in natural waters?
AB  - Microcosm experiments were conducted to examine Fenton reaction-driven
      degradation of three common herbicides exposed to a variety of Fe(2+)-H2O2
      combinations that are likely to be encountered in natural water environments. The
      results show that these combinations had significant (P<0.05) effects on removing
      the water-borne herbicides. This discovery sheds some light on the possible role
      of rainwater-borne H2O2 in inducing Fenton reaction in many natural waters such
      as lakes, streams, estuaries and tidal zones, fishponds and paddy fields that may
      contain ferrous ion at micromolar levels. The research findings obtained from
      this preliminary work provide a rationale for undertaking further study to
      confirm the presence of an overlooked naturally-occurring process that may lead
      to rapid dissipation of many herbicides and other organic pollutants in open
      water environments. Our immediate follow-up work is to continue the laboratory
      scale investigations under more complex experimental conditions, including the
      uses of various natural water samples for the experiments. This will provide a
      basis for future field-based study.

PMID- 23545191
TI  - Denitrification performance and biofilm characteristics using biodegradable
      polymers PCL as carriers and carbon source.
AB  - In this study, a fixed bed bioreactor filled with biopolymer polycaprolactone
      (PCL) was developed to remove nitrate from groundwater through denitrification.
      PCL serves both as carbon source and biofilm carriers. During a long-term
      operation of 561 d, the performance of the reactor in nitrogen removal,
      characteristics of biofilm attached to biodegradable carriers, and the hydrolysis
      and utilization of solid carbon source were studied. With temperatures exceeding
      24  degrees C, the average nitrate concentration in the effluent was lower than
      3.7 mg NL(-1), and more than 95% of TN was removed at hydraulic retention time of
      3-6h. Nitrite and ammonium remained at low levels (less than 0.32 and 0.78 mg NL(
      1), respectively). The calculated PCL amount consumed ranged between 1.6 and 3.7
      g PCL g(-1) NO3-N. The FT-IR spectrum of the used PCL indicated the chain
      scission by hydrolytic degradation. A pyrosequencing analysis of the biofilm
      showed that genus Diaphorobacter belonging to family Comamonadaceae accounted for
      most of the sequences. Bacteria of genera Hydrogenophaga, Rhodocyclaceae
      uncultured and Desulfovibrio were highly enriched in the PCL biofilm.
      Microelectrode data indicated that the biofilm had an average thickness of around
      800 MUm and the intensive denitrification activities occurred in the area of 300
      500 MUm of biofilm with values up to 400 MUmol cm(-3)h(-1).

PMID- 23545192
TI  - Selective tryptophan determination using tryptophan oxidases involved in bis
      indole antibiotic biosynthesis.
AB  - A novel tryptophan assay was developed using tryptophan oxidases. Although many l
      amino acid oxidases (LAAOs) have been reported to catalyze tryptophan oxidation,
      most of them have broad substrate specificity and oxidize multiple amino acids
      besides tryptophan. To obtain a tryptophan-specific LAAO, we focused on bis
      indole antibiotic biosynthesis, a bacterial secondary metabolic pathway. A
      putative LAAO from Streptomyces sp. TP-A0274, StaO involved in staurosporine
      biosynthesis, was heterologously expressed, biochemically characterized, and
      shown to serve as a selective tryptophan oxidase for the first time. In addition,
      another LAAO, VioA involved in violacein biosynthesis in Chromobacterium
      violaceum, was characterized for comparison with StaO. Interestingly, StaO and
      VioA share similar properties, namely narrow substrate specificity and high
      affinity for l-tryptophan, despite the phylogenetic distance between these
      enzymes. Owing to these features, uncommon among known LAAOs, StaO and VioA
      assays can be used for selective and accurate quantification of l-tryptophan via
      a coupled colorimetric reaction. Indeed, StaO and VioA assays provided tryptophan
      concentrations in human plasma as accurately as those obtained by high
      performance liquid chromatography. Therefore, these enzymes were clearly shown to
      offer an effective method for determining tryptophan in biological samples
      rapidly, inexpensively, and accurately. The results shown here also suggest the
      possibility of metabolism-oriented screening as a strategy to obtain enzymes
      highly selective for individual biomolecules.

PMID- 23545193
TI  - Pressure-assisted sample preparation for proteomic analysis.
AB  - Pressure-assisted digestion of proteins, also known as pressure cycling
      technology (PCT), using a Barocycler NEP 2320 was compared with the conventional
      method using atmospheric pressure. Our objective was to demonstrate that PCT
      provides more controlled enzymatic digestion of proteins than prolonged digestion
      at atmospheric pressure ranging from 18 to 24 h. More controlled digestion would
      be beneficial for studies of highly posttranslationally modified protein such as
      histones. For the comparison of these two techniques, recombinant and native
      histone H4 were used as model proteins. PCT was optimized for pressure and time,
      and it was found to be most effective at 15 kpsi for 120 min of incubation. In
      conclusion, the PCT method was found to be much faster than using atmospheric
      pressure. PCT was also found to allow for unambiguous control of digestion
      parameters and to provide a high yield of sequence coverage compared with
      atmospheric pressure.

PMID- 23545194
TI  - Stage IIIA non-small cell lung cancer: morbidity and mortality of three distinct
      multimodality regimens.
AB  - BACKGROUND: Although concurrent chemoradiation therapy can cure stage IIIA non
      small cell lung cancer (NSCLC), studies have demonstrated that anatomic resection
      following high-dose or standard-dose chemoradiation may benefit selected
      patients. We examined morbidity and mortality associated with 3 multimodality
      treatment regimens for stage IIIA disease. METHODS: Institutional databases
      identified patients with stage IIIA (N2) NSCLC who underwent concurrent platinum
      based chemoradiotherapy with or without pulmonary resection between 1998 and
      2011. Exclusion criteria included palliative regimens, sequential
      chemoradiotherapy, radiation-surgery interval greater than 12 weeks, superior
      sulcus tumors, or radiotherapy other than standard external beam radiation.
      Treatment-related morbidity and mortality were examined for the following
      treatment regimens: neoadjuvant chemoradiotherapy with 45 Gy followed by surgery
      (trimodality-45); neoadjuvant chemoradiotherapy with 60 Gy or more followed by
      surgery (trimodality-60); and definitive chemoradiotherapy with 60 Gy or more
      without surgery (D-CRT). RESULTS: During the study period, 144 patients met
      eligibility criteria including 27 trimodality-45, 29 trimodality-60, and 88 D-CRT
      patients. Treatment-related morbidity and mortality rates for D-CRT were 74% [65
      of 88] and 2.3% [2 of 88], respectively. Postoperative morbidity and mortality
      rates for patients who proceeded to surgery were 48% [27 of 56] and 1.8% [1 of
      56], respectively, and did not differ based on dose of neoadjuvant radiation.
      Despite varied anatomic resections and methods of bronchial closure and coverage,
      no bronchopleural fistulae were observed. CONCLUSIONS: Chemoradiotherapy carries
      a significant morbidity profile. However, high-dose neoadjuvant radiation is not
      associated with increased postoperative morbidity or mortality relative to
      standard-dose radiation in patients selected for anatomic resection.

PMID- 23545195
TI  - Does pneumonectomy have a role in the treatment of stage IIIA non-small cell lung
      cancer?
AB  - BACKGROUND: The role of surgical resection for stage IIIA non-small cell lung
      cancer (NSCLC) is unclear. We sought to examine outcomes after pneumonectomy for
      patients with stage IIIA disease. METHODS: All patients with stage IIIA NSCLC who
      had pneumonectomy at a single institution between 1999 and 2010 were reviewed.
      The Kaplan-Meier method was used to estimate long-term survival and multivariable
      Cox proportional hazards regression was used to identify clinical characteristics
      associated with survival. RESULTS: During the study period, 324 patients had
      surgical resection of stage IIIA NSCLC. Pneumonectomy was performed in 55
      patients, 23 (42%) of whom had N2 disease. Induction treatment was used in 17
      patients (31%) overall and in 11 of the patients (48%) with N2 disease.
      Perioperative mortality was 9% (n = 5) overall and 18% (n = 3) in patients that
      had received induction therapy (p = 0.17). Complications occurred in 32 patients
      (58%). Three-year survival was 36% and 5-year survival was 29% for all patients.
      Three-year survival was 40% for N0-1 patients and 29% for N2 patients (p = 0.59).
      In multivariable analysis, age over 60 years (hazard ratio [HR] 3.65, p = 0.001),
      renal insufficiency (HR 5.80, p = 0.007), and induction therapy (HR 2.17, p =
      0.05) predicted worse survival, and adjuvant therapy (HR 0.35, p = 0.007)
      predicted improved survival. CONCLUSIONS: Long-term survival after pneumonectomy
      for stage IIIA NSCLC is within an acceptable range, but pneumonectomy may not be
      appropriate after induction therapy or in patients with renal insufficiency.
      Patient selection and operative technique that limit perioperative morbidity and
      facilitate the use of adjuvant chemotherapy are critical to optimizing outcomes.

PMID- 23545196
TI  - Transcriptome-wide identification of RNA binding sites by CLIP-seq.
AB  - An emergent strategy for the transcriptome-wide study of protein-RNA interactions
      is CLIP-seq (crosslinking and immunoprecipitation followed by high-throughput
      sequencing). We combined CLIP-seq and mRNA-seq to identify direct RNA binding
      sites of eIF4AIII in human cells. This RNA helicase is a core constituant of the
      Exon Junction Complex (EJC), a multifunctional protein complex associated with
      spliced mRNAs in metazoans. Here, we describe the successive steps of the CLIP
      protocol and the computational tools and strategies we employed to map the
      physiological targets of eIF4AIII on human RNAs.

PMID- 23545198
TI  - Skin and soft tissue infection caused by Aeromonas species in cancer patients.

PMID- 23545197
TI  - Flow cytometry based assays for the measurement of apoptosis-associated
      mitochondrial membrane depolarisation and cytochrome c release.
AB  - Mitochondria play a pivotal role in life and death of the cell because they
      produce the majority of energy required for survival and also regulate the
      intrinsic pathway to apoptosis. The involvement of mitochondria in cell death is
      generally measured by following mitochondrial membrane depolarisation or
      mitochondrial outer membrane permeabilisation (MOMP). These events can be assayed
      using cationic dyes that are attracted to the negative charge across the inner
      membrane of healthy mitochondria or by following translocation of cytochrome c
      from the mitochondria to the cytoplasm respectively. These events progress
      rapidly in individual cells but are observed as bi-phasic peaks in flow cytometry
      assays because cell death generally occurs asynchronously in a population. This
      allows researchers to use flow cytometry to easily distinguish healthy cells with
      intact mitochondria healthy from dying cells with permeabilised mitochondria.
      This article will therefore review methods using flow cytometry to follow
      mitochondrial membrane depolarisation and cytochrome c release during apoptosis,
      and will highlight some studies that resulted in development of these assays.

PMID- 23545199
TI  - Intracellular ribonucleases involved in transcript processing and decay:
      precision tools for RNA.
AB  - In order to adapt to changing environmental conditions and regulate intracellular
      events such as division, cells are constantly producing new RNAs while discarding
      old or defective transcripts. These functions require the coordination of
      numerous ribonucleases that precisely cleave and trim newly made transcripts to
      produce functional molecules, and rapidly destroy unnecessary cellular RNAs. In
      recent years our knowledge of the nature, functions and structures of these
      enzymes in bacteria, archaea and eukaryotes has dramatically expanded. We present
      here a synthetic overview of the recent development in this dynamic area which
      has seen the identification of many new endoribonucleases and exoribonucleases.
      Moreover, the increasing pace at which the structures of these enzymes, or of
      their catalytic domains, have been solved has provided atomic level detail into
      their mechanisms of action. Based on sequence conservation and structural data,
      these proteins have been grouped into families, some of which contain only
      ribonuclease members, others including a variety of nucleolytic enzymes that act
      upon DNA and/or RNA. At the other extreme some ribonucleases belong to families
      of proteins involved in a wide variety of enzymatic reactions. Functional
      characterization of these fascinating enzymes has provided evidence for the
      extreme diversity of their biological functions that include, for example,
      removal of poly(A) tails (deadenylation) or poly(U) tails from eukaryotic RNAs,
      processing of tRNA and mRNA 3' ends, maturation of rRNAs and destruction of
      unnecessary mRNAs. This article is part of a Special Issue entitled: RNA Decay
      mechanisms.

PMID- 23545200
TI  - [The quiet, but severe winter is likely gone].

PMID- 23545201
TI  - Raman spectroscopy investigation of load-assisted microstructural alterations in
      human knee cartilage: Preliminary study into diagnostic potential for
      osteoarthritis.
AB  - A preliminary investigation into the diagnostic potential of Raman spectroscopy
      for assessing pathological articular cartilage was conducted. Five arthritic
      human tibial cartilages retrieved after total knee arthroplasty were examined
      using near-infrared (NIR) Raman spectroscopy excited with 647.1nm lines of a Kr
      ion laser. A "healthy" cartilage obtained from cadaver donor was also examined as
      a control sample. Degradation severity was first visually classified into five
      grades (Grade 0-VI) on the surface of both medial and lateral zones in each
      tibial plateau, according to the Collins scale. Raman spectra were then collected
      from selected zones with different damage severity. A systematic increase in
      relative intensity ratio between the Raman bands located at 1241 and 1269cm(-1)
      (amide III doublet) was observed with increasing degradation grades, which could
      be related to structural changes under loading in type II collagen. This finding
      suggests that the present spectroscopic approach might be useful for recognizing
      and quantitatively assessing the degree of osteoarthritis (OA) in its early
      manifestation stage. 

PMID- 23545202
TI  - Microstructure-based constitutive modeling for the large intestine validated by
      histological observations.
AB  - Other than its transport role, the large bowel performs numerous sophisticated
      functions, e.g. water, electrolyte, and vitamin absorption, optimized by its
      contractile properties and passive recoil capacity, but these properties have
      attracted limited attention than has been the case for other parts of the
      gastrointestinal tract. Accordingly, we investigated in vitro the pseudo-elastic
      properties of tubular specimens from the ascending, mid, and descending colon,
      and the rectum of healthy Wistar rats under passive quasi-static conditions and a
      physiologic range of pressures/axial stretches. A neo-Hookean and five-fiber
      family model was chosen as a microstructure-based material model for its
      efficiency in producing accurate representations of the three-dimensional
      inflation/extension data in relation to the underlying microstructure. Guided by
      our optical microscopy observations, this model took account of isotropic elastin
      properties and multi-directional collagen organization, but suffered from
      parameter covariance. Moreover, the contributions to the total model of the neo
      Hookean and circumferential-fiber family were negligible, given the tiny amounts
      of elastin and circumferentially-arranged collagen fibers that were disclosed
      histologically, and the contributions of the diagonal and radial-fiber families
      to data representation were similar. The multiaxial response of the intestinal
      wall was fit equally accurately but without over-parameterization problems by the
      neo-Hookean and three-fiber (diagonal and axial) family model. The preferred
      alignment of collagen fibers towards the axial direction bestowed increased axial
      stiffness to the tissue. The mid colon was the stiffest region by virtue of its
      greatest material parameters, as validated by its higher collagen content than
      that of the distal regions. The present findings generate a more cohesive
      understanding of the large bowel in histomechanical terms, with potential for
      clinical and biomedical applications.

PMID- 23545203
TI  - Thermal-induced residual stresses affect the fractographic patterns of zirconia
      veneer dental prostheses.
AB  - Veneer fractures in dental zirconia-veneer prostheses are more frequent
      clinically than in conventional metal-ceramic systems. This is thought to be due
      to the increased residual stresses generated within the veneer during fabrication
      when zirconia is the infrastructure material. This investigation aimed to analyze
      the fractographic features of fractured zirconia-veneer dental crowns submitted
      to a load-to-failure test and to a more clinically relevant in vitro chewing
      simulation fatigue test. As-sintered and sandblasted zirconia copings were
      veneered with glass-ceramic with different coefficients of thermal expansion and
      cooled following two cooling rates, creating, this way, different levels of
      stresses within the veneer. Crowns with different thermal mismatch combinations
      and different cooling rates were hypothesized to present particular fracture
      patterns. A careful examination of >1000 scanning electron microscopy images of
      the fracture surfaces was conducted in search of characteristic fractographic
      markings of fracture mechanisms connected to the stress state of the veneer.
      Distinctive structural features could be observed between groups veneered with
      the two different glass-ceramics and between fractured crowns under static and
      cyclic loading. The presence/absence of residual stresses zones within the veneer
      have shown to play the major role in the fracture pattern of zirconia-veneer
      dental prostheses. For the fatigue crowns, the zirconia core was never exposed,
      either for sandblasted and as-sintered groups.

PMID- 23545204
TI  - Molecular cloning and characterization of three cryptochrome genes from the fern
      Asplenium yunnanense.
AB  - Cryptochromes are blue light sensing photoreceptors involved in regulating
      various growth and developmental responses in plants. Using degenerate PCR,
      genome-walking and RT-PCR approaches, three full-length genomic sequences of
      cryptochrome genes (CRY1, 2 and 4) were isolated from the fern Asplenium
      yunnanense. These genes encode proteins with 581, 665 and 697 amino acids and are
      similar to Adiantum capillus-veneris blue-light photoreceptor AcCRY1, AcCRY2 and
      AcCRY4 proteins in identity at 83%, 81% and 77%, respectively. Sequence and
      structure analysis indicate that these proteins possess the typical PHR and CCT
      domains characteristic of other higher plant CRYs. Phylogenetic analysis showed
      that the three CRYs were grouped together with the CRYs from A. capillus-veneris,
      which comprise two distinct groups that cluster separately from other plants. 

PMID- 23545206
TI  - High temperature stress monitoring and detection using chlorophyll a fluorescence
      and infrared thermography in chrysanthemum (Dendranthema grandiflora).
AB  - Modern highly insulated greenhouses are more energy efficient than conventional
      types. Furthermore applying dynamic greenhouse climate control regimes will
      increase energy efficiency relatively more in modern structures. However, this
      combination may result in higher air and crop temperatures. Too high temperature
      affects the plant photosynthetic responses, resulting in a lower rate of
      photosynthesis. To predict and analyse physiological responses as stress
      indicators, two independent experiments were conducted, to detect the effect of
      high temperature on photosynthesis: analysing photosystem II (PSII) and stomatal
      conductance (gs). A combination of chlorophyll a fluorescence, gas exchange
      measurements and infrared thermography was applied using Chrysanthemum
      (Dendranthema grandiflora Tzvelev) 'Coral Charm' as a model species. Increasing
      temperature had a highly significant effect on PSII when the temperature exceeded
      38  degrees C for a period of 7 (+/-1.8) days. High temperature decreased the
      maximum photochemical efficiency of PSII (Fv/Fm), the conformation term for
      primary photochemistry (Fv/Fo) and performance index (PI), as well as increased
      minimal fluorescence (Fo). However, at elevated CO2 of 1000 MUmol mol(-1) and
      with a photosynthetic photon flux density (PPFD) of 800 MUmol m(-2) s(-1), net
      photosynthesis (Pn) reached its maximum at 35  degrees C. The thermal index (IG),
      calculated from the leaf temperature and the temperature of a dry and wet
      reference leaf, showed a strong correlation with gs. We conclude that 1)
      chlorophyll a fluorescence and a combination of fluorescence parameters can be
      used as early stress indicators as well as to detect the temperature limit of
      PSII damage, and 2) the strong relation between gs and IG enables gs to be
      estimated non-invasively, which is an important first step in modelling leaf
      temperature to predict unfavourable growing conditions in a (dynamic) semi closed
      greenhouse. 

PMID- 23545205
TI  - Looking for Arabidopsis thaliana peroxidases involved in lignin biosynthesis.
AB  - Monolignol polymerization into lignin is catalyzed by peroxidases or laccases.
      Recently, a Zinnia elegans peroxidase (ZePrx) that is considered responsible for
      monolignol polymerization in this plant has been molecularly and functionally
      characterized. Nevertheless, Arabidopsis thaliana has become an alternative model
      plant for studies of lignification, filling the gaps that may occur with Z.
      elegans. The arabidopsis genome offers the possibility of performing
      bioinformatic analyses and data mining that are not yet feasible with other plant
      species, in order to obtain preliminary evidence on the role of genes and
      proteins. In our search for arabidopsis homologs to the ZePrx, we performed an
      exhaustive in silico characterization of everything from the protein to the
      transcript of Arabidopsis thaliana peroxidases (AtPrxs) homologous to ZePrx, with
      the aim of identifying one or more peroxidases that may be involved in monolignol
      polymerization. Nine peroxidases (AtPrx 4, 5, 52, 68, 67, 36, 14, 49 and 72) with
      an E-value greater than 1e-80 with ZePrx were selected for this study. The
      results demonstrate that a high level of 1D, 2D and 3D homology between these
      AtPrxs and ZePrx are not always accompanied by the presence of the same
      electrostatic and mRNA properties that indicate a peroxidase is involved in
      lignin biosynthesis. In summary, we can confirm that the peroxidases involved in
      lignification are among AtPrx 4, 52, 49 and 72. Their structural and mRNA
      features indicate that exert their action in the cell wall similar to ZePrx. 

PMID- 23545207
TI  - Role of spinal opioid receptor on the antiallodynic effect of intrathecal
      nociceptin in neuropathic rat.
AB  - The purpose of this study was to examine the effects of intrathecal nociceptin
      for neuropathic pain and determine the role of spinal opioid receptor types.
      Neuropathic pain was induced by ligation of L5 and L6 spinal nerves in male
      Sprague-Dawley rats. Several antagonists were intrathecally administered to
      evaluate the action mechanisms of nociceptin: nonselective opioid receptor
      antagonist (naloxone), MU opioid receptor antagonist (CTOP), delta opioid
      receptor antagonist (naltrindole) and kappa opioid receptor antagonist (GNTI).
      The levels of opioid receptor proteins were examined by Western blotting.
      Intrathecal nociceptin produced dose-dependent antiallodynia. Intrathecal
      naloxone reversed the antinociception of nociceptin. Intrathecal CTOP,
      naltrindole and GNTI reversed the antinociceptive effect of nociceptin. Western
      blots showed that the levels of spinal opioid receptor proteins did not differ
      between rats with neuropathic pain and naive rats. Intrathecal nociceptin
      increased the level of delta opioid receptor protein compared with that of nerve
      ligated rats, while the levels of MU, and kappa opioid receptor proteins were
      unchanged. These results suggest that intrathecal nociceptin produced
      antiallodynic effect in spinal nerve ligation-induced neuropathic pain. All three
      types of spinal MU, delta, and kappa opioid receptors were involved in the
      antiallodynic mechanism of nociceptin.

PMID- 23545208
TI  - Streptozotocin-induced diabetes affects the development and maintenance of
      morphine reward in rats.
AB  - Diabetes mellitus is a chronic illness that has been associated with the decrease
      of insulin in type I diabetes. Insulin has an impact not only on the direct
      control of food intake and plasma glucose levels, but also on brain pathways
      associated with reward. It affects brain reward pathways through regulation of
      the dopamine (DA) transporter (DAT). Moreover, it has been found to affect the
      ability of drugs that target the DA system. In the present study, the effects of
      streptozotocin (STZ)-induced diabetes on the acquisition (development) and
      maintenance of morphine-induced conditioned place preference (CPP) were
      investigated in rats. Forty adult male Albino Wistar rats were used in these
      experiments. For induction of diabetes, STZ was administered at a dose of 60
      mg/kg. After seven days, the CPP paradigm was done; conditioning score and
      locomotor activity were recorded by Ethovision software. The results showed that
      diabetes significantly increased the magnitude of conditioning scores,
      acquisition of morphine-induced CPP in compared to naive animals (P<0.05).
      Moreover, in the diabetic group, there were significant differences among
      conditioning scores in the post-conditioning phase and the last four days (7th
      10th), but these differences elongated up to 10 days after the CPP protocol while
      the extinction period was eight days in the naive group. Our findings indicated
      that the magnitude and maintenance of morphine rewarding properties have been
      changed in STZ-induced diabetic animals. It seems that a level of insulin and
      their receptors are involved in the development and maintenance of morphine
      induced CPP in the rats.

PMID- 23545209
TI  - Astrogliosis in the brain of obese Zucker rat: a model of metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a disorder characterized primarily by the
      development of insulin resistance. Insulin resistance and subsequent
      hyperinsulinemia, originating from abdominal obesity, increases the risk of
      cerebrovascular and cardiovascular disease and all-cause mortality. Obesity is
      probably a risk factor for Alzheimer's disease and vascular dementia and is
      associated with impaired cognitive function. The obese Zucker rat (OZR)
      represents a model of type 2 diabetes exhibiting a moderate degree of arterial
      hypertension and of increased oxidative stress. To clarify the possible
      relationships between MetS and brain damage, the present study has investigated
      brain microanatomy in OZRs compared with their littermate controls lean Zucker
      rats (LZRs). Male OZRs and LZRs of 12 weeks of age were used. Their brain was
      processed for immunochemical and immunohistochemical analysis of glial fibrillary
      acidic protein (GFAP). In frontal and parietal cortex of OZRs a significant
      increase in the number of GFAP immunoreactive astrocytes was observed. Similar
      findings were found in the hippocampus, where an increased number of GFAP
      immunoreactive astrocytes were detected in the CA1 and CA3 subfields and dentate
      gyrus of OZRs compared to the LZRs. These findings indicating the occurrence of
      brain injury accompanied by astrogliosis in OZRs suggest that these rats,
      developed as an animal model of type 2 diabetes, may also represent a model for
      assessing the influence of MetS on brain. The identification of neurodegenerative
      changes in OZRs may represent the first step for better characterizing neuronal
      involvement in this model of MetS and possible treatment for countering it.

PMID- 23545210
TI  - Cultural influences on oculomotor inhibition of remote distractors: evidence from
      saccade trajectories.
AB  - This study investigated whether low-level attentional processes as indicated by
      saccade trajectories are modulated by higher-order factors as indicated by
      participants' cultural background. We hypothesized that if the East Asian
      participants engage in context-dependent attentional processing to a greater
      extent than the Western participants, then the magnitude of the distractor effect
      on saccade trajectories (Doyle & Walker, 2001) should be larger with the East
      Asian participants than with the Western participants. Participants executed
      vertical saccades towards targets presented on the vertical meridian above or
      below fixation. Simultaneously with the target, a distractor appeared in one of
      the screen quadrants. Consistently with our hypothesis, we found evidence that
      the saccades of the Chinese participants tended to curve away from the
      distractors more strongly than the saccades of the German participants. However,
      this effect was restricted to the upper distractors and the lower targets. The
      findings are discussed in terms of cross-cultural differences in distractor
      related activation and inhibition and functional specialization of hemifields.

PMID- 23545211
TI  - Community structure of non-coding RNA interaction network.
AB  - Rapid technological advances have shown that the ratio of non-protein coding
      genes rises to 98.5% in humans, suggesting that current knowledge on genetic
      information processing might be largely incomplete. It implies that protein
      coding sequences only represent a small fraction of cellular transcriptional
      information. Here, we examine the community structure of the network defined by
      functional interactions between non-coding RNAs (ncRNAs) and proteins related bio
      macromolecules (PRMs) using a two-fold approach: modularity in bipartite network
      and k-clique community detection. First, the high modularity scores as well as
      the distribution of community sizes showing a scaling-law revealed manifestly non
      random features. Second, the k-clique sub-graphs and overlaps show that the
      identified communities of the ncRNA molecules of H. sapiens can potentially be
      associated with certain functions. These findings highlight the complex modular
      structure of ncRNA interactions and its possible regulatory roles in the cell.

PMID- 23545212
TI  - An integrative clinical database and diagnostics platform for biomarker
      identification and analysis in ion mobility spectra of human exhaled air.
AB  - Over the last decade the evaluation of odors and vapors in human breath has
      gained more and more attention, particularly in the diagnostics of pulmonary
      diseases. Ion mobility spectrometry coupled with multi-capillary columns
      (MCC/IMS), is a well known technology for detecting volatile organic compounds
      (VOCs) in air. It is a comparatively inexpensive, non-invasive, high-throughput
      method, which is able to handle the moisture that comes with human exhaled air,
      and allows for characterizing of VOCs in very low concentrations. To identify
      discriminating compounds as biomarkers, it is necessary to have a clear
      understanding of the detailed composition of human breath. Therefore, in addition
      to the clinical studies, there is a need for a flexible and comprehensive
      centralized data repository, which is capable of gathering all kinds of related
      information. Moreover, there is a demand for automated data integration and semi
      automated data analysis, in particular with regard to the rapid data
      accumulation, emerging from the high-throughput nature of the MCC/IMS technology.
      Here, we present a comprehensive database application and analysis platform,
      which combines metabolic maps with heterogeneous biomedical data in a well
      structured manner. The design of the database is based on a hybrid of the entity
      attribute-value (EAV) model and the EAV-CR, which incorporates the concepts of
      classes and relationships. Additionally it offers an intuitive user interface
      that provides easy and quick access to the platform&rsquo;s functionality:
      automated data integration and integrity validation, versioning and roll-back
      strategy, data retrieval as well as semi-automatic data mining and machine
      learning capabilities. The platform will support MCC/IMS-based biomarker
      identification and validation. The software, schemata, data sets and further
      information is publicly available at http://imsdb.mpi-inf.mpg.de.

PMID- 23545213
TI  - Space-time dynamics of stem cell niches: a unified approach for plants.
AB  - Many complex systems cannot be analyzed using traditional mathematical tools, due
      to their irreducible nature. This makes it necessary to develop models that can
      be implemented computationally to simulate their evolution. Examples of these
      models are cellular automata, evolutionary algorithms, complex networks, agent
      based models, symbolic dynamics and dynamical systems techniques. We review some
      representative approaches to model the stem cell niche in Arabidopsis thaliana
      and the basic biological mechanisms that underlie its formation and maintenance.
      We propose a mathematical model based on cellular automata for describing the
      space-time dynamics of the stem cell niche in the root. By making minimal
      assumptions on the cell communication process documented in experiments, we
      classify the basic developmental features of the stem-cell niche, including the
      basic structural architecture, and suggest that they could be understood as the
      result of generic mechanisms given by short and long range signals. This could be
      a first step in understanding why different stem cell niches share similar
      topologies, not only in plants. Also the fact that this organization is a robust
      consequence of the way information is being processed by the cells and to some
      extent independent of the detailed features of the signaling mechanism.

PMID- 23545214
TI  - Evidence of neurotrophic events due to peritoneal endometriotic lesions.
AB  - To investigate the neurotrophic properties of endometriosis, as well as the
      involvement of neurotrophic factors in the development of chronic pelvic pain in
      patients with endometriosis, we performed a prospective clinical study. The
      presence of neurotrophins was investigated in the peritoneal fluid (PF) of
      patients with peritoneal endometriotic lesions or adenomyosis, as well as from
      women with non-endometriotic adhesions and from women without
      endometriosis/adenomyosis/adhesions. The PF from patients with peritoneal
      endometriotic lesions was divided in three groups: asymptomatic endometriosis,
      minimal pain and severe pain. PF from patients with adenomyosis or with non
      endometriotic adhesions and the control group were divided in patients without
      pain and with pain. Neurotrophin expression in PF was analyzed using Elisa and
      the neuronal growth assay with cultured chicken sensory ganglia (dorsal-root
      ganglia, DRG) and sympathetic ganglia. PF from women with peritoneal
      endometriotic lesions overexpress nerve growth factor (NGF) and neurotrophin-3
      (NT-3), but not brain derived neurotrophic factor (BDNF), whereas the PF of women
      with adenomyosis or adhesions seems to express normal amounts of these factors.
      Neurotrophin expression did not differ among the pain groups. Furthermore, the PF
      from patients with peritoneal endometriotic lesions induced a strong sensory and
      a marginal sympathetic neurite outgrowth, while the PF from women with
      adenomyosis and non-endometriotic adhesions induced an outgrowth similar to the
      control group. The induced neurite outgrowth could only be inhibited in DRG
      incubated with peritoneal endometriotic lesions. Interestingly, the outgrowth of
      sympathetic ganglia was inhibited in all studied groups. The present study
      suggests that only peritoneal endometriotic lesions lead to an increased release
      of NGF and NT-3 into the PF and that NGF modulates the nerve fiber growth in
      endometriosis.

PMID- 23545215
TI  - Serum levels of the adipokine fibroblast growth factor-21 are increased in
      preeclampsia.
AB  - BACKGROUND: Preeclampsia (PE) is a serious cardiovascular complication in
      pregnancy, which is associated with an increased future metabolic and
      cardiovascular risk for mother and newborn. Fibroblast growth factor (FGF)-21 was
      recently introduced as a novel adipokine improving glucose metabolism in vitro
      and in vivo. MATERIAL AND METHODS: We investigated serum FGF-21 levels in
      patients with PE (n=51) as compared to healthy, age-matched controls (n=51)
      during and 6 months after pregnancy. Furthermore, association of FGF-21 with
      markers of renal function, glucose and lipid metabolism, as well as inflammation,
      was elucidated in all individuals. RESULTS: Median maternal FGF-21 serum
      concentrations adjusted for body mass index and gestational age at blood sampling
      were significantly, almost 3-fold increased in PE patients (309.6 ng/l) as
      compared to healthy, age-matched pregnant women (105.2 ng/l) (p<0.001).
      Furthermore, FGF-21 concentrations were independently and positively correlated
      with triglycerides whereas an independent and negative association was observed
      with glomerular filtration rate and low density lipoprotein (LDL) cholesterol in
      pregnant women. Moreover, FGF-21 serum levels significantly decreased in former
      PE patients 6 months after pregnancy approaching levels found in control
      patients. CONCLUSIONS: Maternal FGF-21 serum concentrations are significantly
      increased in PE during pregnancy. Furthermore, triglycerides, glomerular
      filtration rate, and LDL cholesterol are independent predictors of circulating
      FGF-21 in pregnant women.

PMID- 23545216
TI  - Solid phase analytical derivatization as a sample preparation method.
AB  - Analytical derivatization (AD) is an important procedure in analysis as it
      improves the sensitivity, selectivity and chromatographic separation. Solid phase
      analytical derivatization (SPAD) combines extraction and derivatization into a
      single step fulfilling many aspects of a good sample preparation technique, which
      includes low organic solvent consumption, economical, ease of automation with any
      chromatographic system and applicability in a wide range of complicated matrices.
      In this review we have focused on wide applications of SPAD when used in
      combination with different sample preparation methods, such as solid phase
      extraction, ion exchange resins, solid phase microextraction, in-tube,
      microfluidic devices, and hollow fiber extraction methods.

PMID- 23545217
TI  - The host bias of three epiphytic Aeridinae orchid species is reflected, but not
      explained, by mycorrhizal fungal associations.
AB  - PREMISE OF THE STUDY: The three co-occurring epiphytic orchid species,
      Sarcochilus hillii, Plectorrhiza tridentata, and Sarcochilus parviflorus vary in
      host specificity; all are found predominantly on the tree Backhousia myrtifolia
      but some also associate with a broad range of species. Despite this
      specialization, no fitness advantage has been detected for adult orchid plants
      growing on the preferred host. Therefore, we predicted that the host
      specialization of these orchid species is a consequence of a bias toward
      particular orchid mycorrhizal fungi, which are in turn biased toward particular
      woody plant species. METHODS: To test this hypothesis, we sampled representatives
      of each orchid species on B. myrtifolia and other host species across sites.
      Rhizoctonia-like fungi were isolated from orchid roots and identified using
      molecular markers. KEY RESULTS: Three groups of fungi were identified, and the
      orchid species varied in their specificity for these. All fungal groups were
      found on the host B. myrtifolia; yet at all sites, only one orchid species, S.
      hillii, associated with all three groups. CONCLUSIONS: Our results demonstrate
      that these orchid species did vary in their mycorrhizal specificity; however, the
      distribution of their mycorrhizal associates did not directly explain their host
      associations. Rather, we propose that the mycorrhizal relationship of these
      orchid species is complex and have suggested future avenues of research.

PMID- 23545218
TI  - Understanding rice domestication and implications for cultivar improvement.
AB  - Considerable insights were recently gained into the history and process of rice
      domestication. It becomes increasingly clear that artificial and natural
      selections coupled with extensive introgression have shaped the genomes of
      cultivated rice. The interplay of these evolutionary forces gave rise to the
      cultivated species, Oryza sativa, with divergent genomic backgrounds from two
      wild species, O. rufipogon and O. nivara, governed by a set of domestication
      alleles which had originated primarily at one location of initial cultivation.
      The mechanistic understanding of domestication suggests that the combination of
      quantitative trait locus mapping, genome-wide association study, and genome scan
      will be effective means for discovering potentially valuable alleles from the
      cultivated and wild species. The accumulation and appropriate sampling of
      germplasm collections for these analyses should effectively grow the useful
      allele pool, which combined with molecular breeding may get to a point literally
      triggering the re-domestication of rice varieties for sustainable food
      production.

PMID- 23545219
TI  - Hydraulic signals in long-distance signaling.
AB  - Higher plants are sessile organisms that continuously adapt their metabolism and
      development in response to a changing environment. Control of water uptake and
      the maintenance of water status are key for the survival and optimal growth of
      plants. Environmental factors such as radiation, air temperature, rainfall, and
      humidity have a high impact on plant water relations. Hence, plants require a
      coordinated and timely response in above-ground and below-ground organs to cope
      with the changing need to take up and preserve water. In this review we will
      focus on changes in plant water availability and on how information on the water
      status is communicated to remote plant organs. We will summarize the current
      knowledge of long-distance signaling by hydraulic cues and of potential sensors
      required to convert a physical signal into a chemical messenger, namely the plant
      hormone abscisic acid (ABA).

PMID- 23545220
TI  - Cholesterol favors the emergence of a long-range autocorrelated fluctuation
      pattern in voltage-induced ionic currents through lipid bilayers.
AB  - The present paper was aimed at evaluating the effect of cholesterol (CHO) on the
      voltage-induced lipid pore formation in bilayer membranes through a global
      characterization of the temporal dynamics of the fluctuation pattern of ion
      currents. The bilayer model used was black lipid membranes (BLMs) of
      palmitoyloleoylphosphatidylethanolamine and palmitoyloleoylphosphatidylcholine
      (POPE:POPC) at a 7:3 molar ratio in the absence (BLM0) or in the presence of 30
      (BLM30), 40 (BLM40) or 50(BLM50)mol% of cholesterol with respect to total
      phospholipids. Electrical current intensities (I) were measured in voltage
      (DeltaV) clamped conditions at DeltaV ranging between 0 and +/-200mV. The
      autocorrelation parameter alpha derived from detrended fluctuation analysis (DFA)
      on temporal fluctuation patterns of electrical currents allowed discriminating
      between non-correlated (alpha=0.5, white noise) and long-range correlated
      (0.5<alpha<1) behaviors. The increase in |DeltaV| as well as in cholesterol
      content increased the number of conductance states, the magnitude of conductance
      level, the capacitance of the bilayers and increased the tendency towards the
      development of long-range autocorrelated (fractal) processes (0.5<alpha<1) in
      lipid channel generation. Experiments were performed above the phase transition
      temperature of the lipid mixtures, but compositions used predicted a superlattice
      like organization. This leads to the conclusion that structural defects other
      than phase coexistence may promote lipid channel formation under voltage clamped
      conditions. Furthermore, cholesterol controls the voltage threshold that allows
      the percolation of channel behavior where isolated channels become an
      interconnected network.

PMID- 23545221
TI  - Middle Miocene Pierolapithecus provides a first glimpse into early hominid pelvic
      morphology.
AB  - Here we describe the pelvis from the holotype specimen of Pierolapithecus
      catalaunicus (IPS-21350), a middle Miocene (11.9 Ma [millions of years ago]) stem
      hominid from Barranc de Can Vila 1 in Abocador de Can Mata (Catalonia, Spain) for
      which a partial skeleton is preserved. This skeleton includes the oldest known
      great ape pelvic materials, which have implications for reconstructing the basal
      hominid body plan from which later hominids evolved. The P. catalaunicus pelvis
      is composed of a fragment from the ilium (IPS-21350.38) and one from the ischium
      (IPS-21350.39). Although the P. catalaunicus ischium consists of just a small
      fragment from the caudal acetabulum, the preserved morphology is consistent with
      the basal hominoid Proconsul nyanzae. The ilium is similar to Pr. nyanzae in its
      concave gluteal surface and linea arcuata form, which suggests much of the iliac
      and pubic form was primitive. However, the ilium was relatively more flaring than
      Pr. nyanzae and most monkeys, and could be within the range of extant lesser
      apes. In addition, the iliac tuberosity width was probably intermediate between
      extant great apes and monkeys, although maximum and minimum estimates could be
      accommodated within either group. The P. catalaunicus ilium reflects incipient
      modifications of the basal hominoid torso for the more frequent use of orthograde
      behaviors described for this taxon on the basis of other preserved anatomical
      regions, and also supports claims that extant ape pelvic morphology could be
      homoplastic given the hypothesized phylogenetic positions of Pierolapithecus.

PMID- 23545222
TI  - Nievesia sossisensis, a new anchomomyin (Adapiformes, Primates) from the early
      Late Eocene of the southern Pyrenees (Catalonia, Spain).
AB  - A new genus and species attributed to the tribe Anchomomyini is described from
      the early Late Eocene locality of Sossis (MP17a), one of the most important
      Paleogene fossil sites from the Iberian Peninsula. Nievesia sossisensis is
      characterized by its buccolingually compressed P(4) and its upper molars with no
      pericone, medium-sized hypocone, straight postcingulum and minuscule mesostyle,
      and the extremely reduced metacone on the M(3). Its lower dentition presents a P4
      with an incipient metaconid, lower molars with no paraconid and a premetacristid
      closing the trigonid basin, and M3 with the trigonid wider than the talonid.
      Phylogenetic analyses suggest a close relationship between Nievesia and
      Mazateronodon, although the new genus is also related to Anchomomys and, to a
      lesser extent, Buxella and Periconodon. These analyses, which also include
      djebelemurines, no longer relate European anchomomyins with crown strepsirhines,
      and suggest their closer relationship with asiadapines and sivaladapids.

PMID- 23545223
TI  - A flange on electron spectromicroscope with spherical deflector analyzer-
      simultaneous imaging of reciprocal and real spaces.
AB  - An instrumental realization of the idea for the electron emission
      spectromicroscope based on the newly developed imaging energy filter called alpha
      SDA (Spherical Deflector Analyzer) is reported. Its compact design enables the
      realization of the flange-on spectromicroscope concept. It is equipped with two
      independent energy selective imaging channels: one for real and another for
      reciprocal space visualization. These images can be acquired quasi
      simultaneousely by means of the software based on the switching on and off
      potentials of the energy filter. An electron gun located inside the immersion
      objective lens allows a new kind of sample illumination by high energy primary
      electrons and thus, opens a new application field for electron spectromicroscopy
      under laboratory conditions. 

PMID- 23545224
TI  - Effects of Fam83h overexpression on enamel and dentine formation.
AB  - OBJECTIVE: The aim of this study was to determine if FAM83H over-expression
      causes dentine or enamel malformations. MATERIALS AND METHODS: The full-length
      mouse Fam83h cDNA was inserted into the pCAGIG vector between a beta-actin
      promoter and beta-globin enhancer for ubiquitous expression in transgenic mice.
      Recombinant mouse FAM83H was expressed and used to generate polyclonal
      antibodies. Western blots showed enhanced expression of the Fam83h transgene. The
      effects of transgene expression on tooth development were assessed by
      microhardness measurements of enamel and dentine. Total thickness of incisor
      enamel at the level of the alveolar crest was measured and decussating rod
      patterns were visualized by scanning electron microscopy (SEM). RESULTS: Three
      transgenic mouse lines were selected based upon their transgene expression
      levels. There was no statistically significant difference in the Vickers
      microhardness values of enamel or dentine between the transgenic lines or between
      the transgenic lines and wild type mice. No statistically significant differences
      in enamel thickness were observed between the transgenic lines and the wild type
      mice. SEM analysis revealed no apparent differences in the enamel crystal and rod
      morphologies. CONCLUSION: Our findings demonstrate that over-expression of FAM83H
      in mice does not produce a phenotype in dentine or enamel.

PMID- 23545225
TI  - Expression of curcin-transferrin receptor binding peptide fusion protein and its
      anti-tumor activity.
AB  - Curcin can inhibit the proliferation of tumor cells and promote tumor cell
      apoptosis, but the cytotoxicity of curcin is not selective for tumors or normal
      cells. In order to enhance the targeting of the anti-tumor ability of curcin, a
      transferrin receptor (TfR) binding peptide, TfRBP9, was fused with curcin. The
      curcin-TfRBP9 gene was cloned into pQE-30 and the recombinant vector pQE-30
      curcin-TfRBP9 was established. Then the recombinant vector pQE-30-curcin-TfRBP9
      was transferred into Escherichia coli M15. After being induced by 0.5mM IPTG for
      6h at 37 degrees C, the expressed quantity of the recombinant protein was about
      30% of the total protein. Recombinant curcin-TfRBP9 was expressed in the form of
      an inclusion body. After dissolution, purification and renaturation, the purity
      of the recombinant curcin-TfRBP9 reached 95%. Immunofluorescence analysis showed
      that the TfRBP9 significantly enhanced the ability of the curcin binding to
      HepG2, and was enriched in the cytoplasm. The curcin-TfRBP9 fusion protein had
      significant proliferation inhibition effects on the HepG2 cells that over
      expressed transferrin receptors, had lower inhibitory effects on the SKBR-3 cells
      that expressed low transferrin receptors, and had the lowest inhibitory effects
      on the LO-2 cells that were normal human liver cells. Compared with curcin, the
      curcin-TfRBP9 induced higher apoptosis rates in the HepG2 cells.

PMID- 23545226
TI  - Practice of split-thickness skin graft storage and histological assessment of
      tissue quality.
AB  - Storage of split-thickness skin grafts (STSGs) represents a standard procedure in
      burn surgery. The purpose of this study was to evaluate clinical routine of STSG
      preservation. Further, we aimed at investigating the effect of storage on tissue
      integrity and cell viability, proliferation, apoptosis and vascularization. A
      survey was performed among plastic surgery centres in Europe. STSGs were
      harvested from healthy patients and analysed by histology (HE, Verhoeff's,
      Masson's Trichrome, Sirius Red) and immunohistochemistry (Ki67, TUNEL, CD31).
      Cell viability was determined by MTT assay. The survey revealed that storage of
      STSGs up to 10 days is common practice. STSGs mostly were stored at 4  degrees C
      in saline-moisturized gauze. Histology showed no disintegration of the tissue or
      a decrease of collagen and elastic fibres. Proliferation increased to 22.5% of
      total cells after 3 days. On day 7 of STSG storage apoptotic cells amounted for
      25% of total cells. Cell viability decreased by 50% after day 3 of storage. Even
      though reportedly superior methods for skin grafts storage exist, most study
      participants applied the simplest method of storage. Our data underscore this
      practice. However, a reduced cell viability after 3 days of storage may have an
      influence on graft healing.

PMID- 23545227
TI  - HIV-associated lipodystrophy in South Africa: the impact on the patient and the
      impact on the plastic surgeon.
AB  - BACKGROUND: With 67% of the world's human immunodeficiency virus (HIV)-infected
      population existing in sub-Saharan Africa and recent access to highly active
      antiretroviral therapy (HAART), the demand for plastic surgical intervention in
      addressing lipodystrophy has expanded dramatically. We assessed the rate of
      lipodystrophy in a random clinic cohort, the demand for surgical correction and
      risk of treatment non-compliance. METHOD: Questionnaire and database cross
      sectional review of 554 patients over a 3-month period at the Themba Lethu
      Clinic, Johannesburg, South Africa. RESULTS: A total of 479 patients completed
      the questionnaire, 83% were female. Nearly 90% of patients were on, or had been
      on, stavudine (d4T). The prevalence of lipodystrophy was 11.7%. Nearly 5.9% of
      patients had considered stopping treatment due to the development of
      lipodystrophy; 47% would consider surgery to correct unwanted physical changes.
      Male patients were satisfied by the changes they noted in their physical features
      following treatment (pre-treatment satisfaction 38% vs. post-treatment
      satisfaction of 94%). Female patients had 6.5 times more breast hypertrophy
      related symptoms than in their pre-treatment state. CONCLUSION: We identify a
      prevalence of 11.7% of patients with HIV-associated lipodystrophy, of whom 5.9%
      would consider non-compliance on the basis of this side effect alone. The demand
      for surgical correction is significant and needs to be addressed.

PMID- 23545229
TI  - Skeletal site-specific effects of whole body vibration in mature rats: from
      deleterious to beneficial frequency-dependent effects.
AB  - Whole body vibration (WBV) is receiving increasing interest as an anti
      osteoporotic prevention strategy. In this context, selective effects of different
      frequency and acceleration magnitude modalities on musculoskeletal responses need
      to be better defined. Our aim was to investigate the bone effects of different
      vibration frequencies at constant g level. Vertical WBV was delivered at 0.7 g
      (peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats
      10 min daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or
      bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed
      similar values between adjacent skin and bone sites. Local accelerations were
      greater at 8 Hz compared with 52 and 90 Hz and were greater in vertebra than
      tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen
      in L2 vertebral body and were characterized by trabecular reorganization and
      stimulated mineral apposition rate (MAR) without any bone volume alteration. At
      90 Hz, axial and appendicular skeletons were affected as were the cortical and
      trabecular compartments. Cortical thickness increased in femur diaphysis (17%)
      along with decreased porosity; trabecular bone volume increased at distal femur
      metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased
      SMI and increased trabecular connectivity. Trabecular thickness increased at the
      tibia proximal metaphysis. Bone cellular activities indicated a greater bone
      formation rate, which was more pronounced at vertebra (300%) than at long bone
      (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however,
      hyperosteoidosis with reduced MAR along with increased resorption surfaces
      occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also
      seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and
      tibia. Thus the most favorable regimen is 90 Hz, while deleterious effects were
      seen at 8 Hz. We concluded that the skeleton is frequency-scalable, thus
      highlighting the importance of WBV regimen conditions and suggesting that
      cautions are required for frequencies less than 10 Hz, at least in rats.

PMID- 23545228
TI  - Modeling hepatic osteodystrophy in Abcb4 deficient mice.
AB  - Hepatic osteodystrophy (HOD) denotes the alterations in bone morphology and
      metabolism frequently observed in patients with chronic liver diseases, in
      particular in case of cholestatic conditions. The molecular mechanisms underlying
      HOD are only partially understood. In the present study, we characterized the
      bone phenotypes of the ATP-binding cassette transporter B4 knockout mouse (Abcb4(
      /-)), a well-established mouse model of chronic cholestatic liver disease, with
      the aim of identifying and characterizing a mouse model for HOD. Furthermore, we
      investigated the influence of vitamin D on bone quality in this model. The bone
      morphology analyses revealed reduced bone mineral contents as well as changes in
      trabecular bone architecture and decreased cortical bone densities in Abcb4(-/-)
      mice with severe liver fibrosis. We observed dysregulation of genes involved in
      bone remodeling (osteoprotegerin, osteocalcin, osteopontin) and vitamin D
      metabolism (7-dehydrocholesterol reductase, Gc-globulin, Cyp2r1, Cyp27a1) as well
      as alterations in calcium and vitamin D homeostasis. In addition, serum RANKL and
      TGF-beta levels were increased in Abcb4(-/-) mice. Vitamin D dietary intervention
      did not restore the bone phenotypes of Abcb4(-/-) animals. We conclude that the
      Abcb4(-/-) mouse provides an experimental framework and a preclinical model to
      gain further insights into the molecular pathobiology of HOD and to study the
      systemic effects of therapeutic interventions.

PMID- 23545231
TI  - [Quality of life in diabetes mellitus assessed on the basis of Hungarostudy
      Health Panel survey].
AB  - INTRODUCTION: Examining the quality of life has a great importance in the
      treatment of chronic patients. AIM: The aim of the authors was to assess the
      national status on the basis of the database of the Hungarostudy Health Panel
      using statistical evaluation. METHODS: Three validated questionnaries in the test
      battery served as instruments: the shortened version of the WHO Well-being
      Questionnaire, the Shortened Beck's Depression Scale Rating and the Illness
      Intrusiveness Rating Scale. RESULTS: It was found that in accordance with
      international data, the quality of life index of Hungarian diabetic patients was
      significantly worse than that of the non-diabetic population. CONCLUSIONS:
      International data also show that the decline in quality of life is correlated
      with a decline of cooperation and life expectancy of diabetic patients. This
      explains why methods of behavioral medicine focusing on improving life quality
      are of great importance, that have not yet been considered currently in
      psychoeducation. Referring to international examples the authors make a proposal
      on an extensive survey among Hungarian diabetic patients with the help of
      validated disease-specific questionnaires and using Transtheoretical Model in
      order to make education more efficient.

PMID- 23545230
TI  - [Methods and conditions of fertility preservation in early-stage ovarian tumors].
AB  - The aim of this study is to review the literature of fertility-sparing techniques
      and their safety in early-stage malignant ovarian tumors, especially in
      epithelial ovarian cancer. Fertility preservation is widely accepted in early
      stage borderline, germ cell and sex cord-stromal tumors. Based on data from
      retrospective studies, fertility-sparing surgery in epithelial ovarian cancer can
      be recommended in stage IA, grade 1-2 and favorable hystologic type ovarian
      cancer. Above stage IA, or in grade 3, or in clear-cell tumors decision making
      process about fertility-sparing surgery should be individual. Correct surgical
      staging is mandatory and oncologic safety should be of primary importance. In the
      group of carefully selected patients oncological outcomes are identical to those
      of radical surgery. Spontaneous pregnancy rates vary, but they are generally
      high. Adequate counseling with patients, detailed documentation and careful
      follow-up is of outstanding importance. In order to improve the quality of
      fertility preservation techniques, establishment of treatment centers is
      recommended.

PMID- 23545232
TI  - [Mineral content of some herbs and plant extracts with anti-inflammatory effect
      used in gastrointestinal diseases].
AB  - INTRODUCTION: In gastrointestinal diseases folk medicine usually recommends herbs
      and teas with antiinflammatory activities, especially mucilage and bitter agent
      containing plants. The use of stomatics as adjuvant therapy in medical practice
      is frequent. AIM: The authors explored the mineral element content of some herbs,
      because mineral elements may have significant role in the development and
      treatment of gastrointestinal diseases, and a close connection between the
      presence or absence of mineral elements and inflammatory mediators was noted.
      METHODS: The mineral content in Trigonellae foenugraeci semen, Farfarae folium et
      flos, Taraxaci radix and Cichorii radix and teas prepared from these herbs was
      determined using inductively coupled plasma optical emission spectrometry. The
      results were evaluated from nutritional and biomedical points of view. RESULTS:
      Farfarae folium et flos tea was found to be a rich source of calcium, chromium,
      manganese and molybdenum. Trigonellae foenugraeci semen, Taraxaci radix and
      Cichorii radix displayed favourable calcium to magnesium ratio (1-1.5) and they
      contained other elements (manganese, iron, copper, zinc) which may have
      significant role in the immune defence system. CONCLUSION: The beneficial
      therapeutic effect of the studied herbs may be related to their mineral element
      content.

PMID- 23545233
TI  - [Carcinoid heart disease].
AB  - Carcinoids are rare tumors originating from neuroendocrine cells. A large
      proportion of these tumors produce serotonin and other biologically active
      hormones which may produce carcinoid syndrome characterized by flushing,
      diarrhoea and bronchospasm. Carcinoid heart disease, a rare complication of
      carcinoid syndrome, may itself have a great impact on life expectancy of patients
      with carcinoid syndrome. The authors present a case history of a patients with
      carcinoid heart disease and they review the symptoms, diagnosis and therapeutic
      options of this rare complication of carcinoid syndrome.

PMID- 23545234
TI  - [The Institute of Pathology in Budapest was first named Experimental Cancer
      Research Institute in 1934].

PMID- 23545236
TI  - [Bone biomarkers in haemodialysis patients: bone alkaline phosphatase or beta
      Crosslaps?].
AB  - BACKGROUND: Bone turnover (BT) abnormalities are frequently observed in patients
      with chronic kidney disease. Bone biopsy remains the gold standard for diagnosis;
      however, its invasive nature has led to its decreased utilisation. The serum
      parathyroid hormone (PTH) level is not a reliable bone marker (BM) for BT
      assessment. The latest international recommendations suggest the use of total
      alkaline phosphatase (t-ALP) or bone-specific alkaline phosphatase (b-ALP), but
      not beta-CrossLaps (CTX). We compared b-ALP, t-ALP, and CTX levels in patients on
      haemodialysis (HD). METHODS: All HD patients at a single institution following a
      standard 3*4 to 3*5 hours schedule were included in the study, provided they were
      free from liver disease. Serum intact PTH, t-ALP, b-ALP, and CTX values were
      compared at baseline and after 18 months of treatment. A kinetic study was
      performed for pre- and postdialysis CTX values over a 2-week period. We described
      the longitudinal evolution of these BMs in two typical patients. RESULTS: A total
      of 98 patients on HD (46% female) were evaluated. The mean age was 69.8+/-11
      years and the mean duration of dialysis was 54.4+/-61 months. At baseline, CTX
      (2.1+/-1 MUg/L) correlated well with b-ALP (18+/-11 MUg/L; r=0.64; P<0.001) and
      PTH (221+/-165 pg/mL; r=0.62; P<0.001). The changes in these values at 18 months
      were also correlated (DeltaCTX compared with Deltab-ALP: r=0.51; P<0.001; Deltab
      ALP compared with DeltaPTH: r=0.37, P<0.01). b-ALP and t-ALP (245+/-132 U/L) were
      closely correlated (r=0.78), as was their variation over 18 months (r=0.67), but
      t-ALP did not correlate with PTH, and correlated poorly with CTX (r=0.38). The
      CTX reduction ratio during standard dialysis was approximately 70 to 75% over
      each session, although predialysis values remained stable. CONCLUSION: In HD
      patients, mean CTX values are five times higher than the normal range. CTX
      appears to be an alternative to b-ALP for assessing BT. b-ALP remains the
      standard BM, despite being expensive, infrequently available in many
      laboratories, and not useful for patients with liver disease.

PMID- 23545237
TI  - Magnetoencephalography reveals altered auditory information processing in youth
      with obsessive-compulsive disorder.
AB  - Patients with obsessive-compulsive disorder (OCD) often report sensory
      intolerances which may lead to significant functional impairment. This study used
      auditory evoked fields (AEFs) to address the question of whether neural
      correlates of sensory auditory information processing differ in youth with OCD
      compared with healthy comparison subjects (HCS). AEFs, recorded with a whole head
      275-channel magnetoencephalography system, were elicited in response to binaural
      auditory stimuli from 10 pediatric subjects with OCD (ages 8-13, mean 11 years, 6
      males) and 10 age- and gender-matched HCS. Three major neuromagnetic responses
      were studied: M70 (60-80 ms), M100 (90-120 ms), and M150 (130-190 ms). When
      compared with HCS, subjects with OCD demonstrated delayed latency of the M100
      response. In subjects with OCD the amplitude of the M100 and M150 responses was
      significantly greater in the right hemisphere compared with the left hemisphere.
      Current results suggest that when compared with HCS, subjects with OCD have
      altered auditory information processing, evident from the delayed latency of the
      M100 response, which is thought to be associated with the encoding of physical
      stimulus characteristics. Interhemispheric asymmetry with increased M100 and M150
      amplitudes over the right hemisphere compared with the left hemisphere was found
      in young OCD subjects. These results should be interpreted with caution due to
      the high variability rate of responses in both HCS and OCD subjects, as well as
      the possible effect of medication in OCD subjects.

PMID- 23545238
TI  - In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by
      (13)C turnover from hyperpolarized [1-(13)C]acetate to [1-(13)C]acetylcarnitine.
AB  - BACKGROUND: Acetate metabolism in skeletal muscle is regulated by acetylCoA
      synthetase (ACS). The main function of ACS is to provide cells with acetylCoA, a
      key molecule for numerous metabolic pathways including fatty acid and cholesterol
      synthesis and the Krebs cycle. METHODS: Hyperpolarized [1-(13)C]acetate prepared
      via dissolution dynamic nuclear polarization was injected intravenously at
      different concentrations into rats. The (13)C magnetic resonance signals of [1
      (13)C]acetate and [1-(13)C]acetylcarnitine were recorded in vivo for 1min. The
      kinetic rate constants related to the transformation of acetate into
      acetylcarnitine were deduced from the 3s time resolution measurements using two
      approaches, either mathematical modeling or relative metabolite ratios. RESULTS:
      Although separated by two biochemical transformations, a kinetic analysis of the
      (13)C label flow from [1-(13)C]acetate to [1-(13)C]acetylcarnitine led to a
      unique determination of the activity of ACS. The in vivo Michaelis constants for
      ACS were KM=0.35+/-0.13mM and Vmax=0.199+/-0.031MUmol/g/min. CONCLUSIONS: The
      conversion rates from hyperpolarized acetate into acetylcarnitine were quantified
      in vivo and, although separated by two enzymatic reactions, these rates uniquely
      defined the activity of ACS. The conversion rates associated with ACS were
      obtained using two analytical approaches, both methods yielding similar results.
      GENERAL SIGNIFICANCE: This study demonstrates the feasibility of directly
      measuring ACS activity in vivo and, since the activity of ACS can be affected by
      various pathological states such as cancer or diabetes, the proposed method could
      be used to non-invasively probe metabolic signatures of ACS in diseased tissue.

PMID- 23545240
TI  - Body composition and fitness in the obesity paradox--body mass index alone does
      not tell the whole story.

PMID- 23545239
TI  - Evasion from accelerated blood clearance of nanocarrier named as "Lactosome"
      induced by excessive administration of Lactosome.
AB  - BACKGROUND: Nanoparticle of Lactosome, which is composed of poly(l-lactic acid)
      base depsipeptide with diameter of 35nm, accumulates in solid tumors by the
      enhanced permeability and retention (EPR) effect. However, a pharmacokinetic
      alteration of Lactosome was observed when Lactosome was repeatedly administered.
      This phenomenon is named as the Lactosome accelerated blood clearance (ABC)
      phenomenon. In this study, the effect of Lactosome dose on the ABC phenomenon was
      examined and discussed in terms of immune tolerance. METHODS: To tumor
      transplanted mice, Lactosome (0-350mg/kg) was administrated. At 7days after the
      first administration, indocyanine green (ICG)-labeled Lactosome (ICG-Lactosome, 0
      350mg/kg) was injected. Near-infrared fluorescence imaging was performed, and
      biodistribution of ICG-Lactosome was evaluated. Further, the produced amounts of
      anti-Lactosome IgM were determined by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: ICG-Lactosome accumulated in the tumor region when the first Lactosome
      dose exceeded over 150mg/kg. The amounts of anti-Lactosome IgM were inversely
      correlated with the first Lactosome doses. Even after establishment of the
      Lactosome ABC phenomenon with the first Lactosome dose as low as 5.0mg/kg, the
      Lactosome ABC phenomenon can be evaded apparently by dosing ICG-Lactosome over
      50mg/kg regardless of anti-Lactosome IgM production. CONCLUSIONS: There are two
      different mechanisms for evasion from the Lactosome ABC phenomenon before and
      after its establishment. In either mechanism, however, the Lactosome ABC
      phenomenon can be evaded by excessive administration of Lactosome. GENERAL
      SIGNIFICANCE: Lactosome is a potential nanocarrier for drug and/or imaging agent
      delivery, which can be used for frequent administrations without significant
      pharmacokinetic alterations.

PMID- 23545241
TI  - Re: a new discussion for "The projected effect of increasing physical activity on
      reducing the prevalence of common mental disorders among Canadian men and women:
      a national population-based community study".

PMID- 23545242
TI  - Fabrication of amphiphobic surface by using titanium anodization for large-area
      three-dimensional substrates.
AB  - Superamphiphobic functional Ti foils were fabricated using anodization
      techniques. By varying the supply voltage and anodization time, a two-step
      anodization method was used to maximize the contact angle of water and various
      oils. The morphology of the TiO2 nanotube surface is important to achieve
      superamphiphobicitiy. The anodized surface maintained good superamphiphobic
      stability with long-term storage. Furthermore, the wettability properties toward
      both water and various oils can be easily and reversibly switched from
      hydrophobic and oleophobic to hydrophilic and oleophilic, respectively, and vice
      versa via air-plasma treatment and fluorination. The developed simple technique
      can be applied to any large-area three-dimensional surfaces to fabricate
      amphiphobic Ti surfaces.

PMID- 23545243
TI  - Using the pseudophase kinetic model to interpret chemical reactivity in ionic
      emulsions: determining antioxidant partition constants and interfacial rate
      constants.
AB  - Kinetic results obtained in cationic and anionic emulsions show for the first
      time that pseudophase kinetic models give reasonable estimates of the partition
      constants of reactants, here t-butylhydroquinone (TBHQ) between the oil and
      interfacial region, P(O)(I), and the water and interfacial region, P(W)(I), and
      of the interfacial rate constant, k(I), for the reaction with an arenediazonium
      ion in emulsions containing a 1:1 volume ratio of a medium chain length
      triglyceride, MCT, and aqueous acid or buffer. The results provide: (a) an
      explanation for the large difference in pH, >4 pH units, required to run the
      reaction in CTAB (pH 1.54, added HBr) and SDS (pH 5.71, acetate buffer)
      emulsions; (b) reasonable estimates of PO(I) and k(I) in the CTAB emulsions; (c)
      a sensible interpretation of added counterion effects based on ion exchange in
      SDS emulsions (Na(+)/H3O(+) ion exchange in the interfacial region) and Donnan
      equilibrium in CTAB emulsions (Br(-) increasing the interfacial H3O(+)); and (d)
      the significance of the effect of the much greater solubility of TBHQ in MCT
      versus octane, 1000/1, as the oil. These results should aid in interpreting the
      effects of ionic surfactants on chemical reactivity in emulsions in general and
      in selecting the most efficient antioxidant for particular food applications.

PMID- 23545244
TI  - Multiscale entropy analysis of electroencephalography during sleep in patients
      with Parkinson disease.
AB  - Sleep disorders are frequently seen in patients with Parkinson disease (PD),
      including rapid eye movement (REM) behavior disorder and periodic limb movement
      disorder. However, knowledge about changes in non-REM sleep in patients with PD
      is limited. This study explored the characteristics of electroencephalography
      (EEG) during sleep in patients with PD and non-PD controls. We further conducted
      multiscale entropy (MSE) analysis to evaluate and compare the complexity of sleep
      EEG for the 2 groups. There were 9 patients with PD (Hoehn-Yahr stage 1 or 2) and
      11 non-PD controls. All participants underwent standard whole-night
      polysomnography (PSG), which included 23 channels, 6 of which were for EEG. The
      raw data of the EEG were extracted and subjected to MSE analysis. Patients with
      PD had a longer sleep onset time and a higher spontaneous EEG arousal index.
      Sleep stage-specific increased MSE was observed in patients with PD during non
      REM sleep. The difference was more marked and significant at higher time scale
      factors (TSFs). In conclusion, increased biosignal complexity, as revealed by MSE
      analysis, was found in patients with PD during non-REM sleep at high TSFs. This
      finding might reflect a compensatory mechanism for early defects in neuronal
      network control machinery in PD. 

PMID- 23545245
TI  - Lambda waves and occipital generators.
AB  - The objective of this study was to identify the relationship between lambda waves
      (LWs) and other occipital waveforms, in a retrospective analysis of
      electroencephalograms (EEGs) of clinic and hospitalized patients at a single
      center. The LWs were correlated with alpha rhythm, photic driving, and positive
      occipital sharp transients of sleep (POSTS). A computer-generated cursor
      quantified amplitude and duration of POSTS and LWs (3 waveforms and both
      hemispheres). Fisher exact test was used for significance (P <= .05). A total of
      116 patients were evaluated. Of 111 patients, with interpretable results, 74
      (66.67%) had visual scanning during EEG, with 37 (50.0%) having LWs. The LWs
      (17.69 uV) were consistently smaller than POSTS (31.40 uV) despite similar
      morphology. Patients with an alpha rhythm of >8.5 Hz were strongly correlated
      with the presence of LWs (P < .0001), and those with LWs were strongly predictive
      of normal EEG (P = .001). Of the 37 patients, 27 (73.0%) with LWs had photic
      driving (P = .0496). No correlation was found between LWs and POSTS (P = .45).
      The presence of LWs and a low normal posterior dominant rhythm (PDR) suggests
      intact electrocerebral health. LWs and the photic driving response suggest
      similar generators but stimulus-specific networks. POSTS differ from LWs despite
      similar morphology, suggesting different network activation of occipital
      generators. LWs have clinical significance in excluding encephalopathy. Occipital
      generators are differentiated by state and stimulus-dependent network activation
      and not by location and morphology. 

PMID- 23545246
TI  - Meta-analytic review of P3 components in posttraumatic stress disorder and their
      clinical utility.
AB  - Patients with posttraumatic stress disorder (PTSD) exhibiting disturbances in
      information processing, including trouble with attention, were studied. Event
      related potentials (ERPs)-specifically, the P3 components (P3a, P3b, and P3
      working memory {P3wm})-provide an objective, non-invasive, and cost-effective
      method for evaluating such disturbances. We evaluated the potential clinical
      utility of P3 components by examining the differences between PTSD and several
      control groups: normal participants, non-PTSD patients with trauma, and medicated
      patients with PTSD. We performed a meta-analysis of the ERP literature between
      1990 and 2010 using a random effects model. P3a amplitude was larger in patients
      with PTSD compared to non-PTSD patients having trauma in the context of trauma
      related distracters. P3b amplitude was also larger in patients with PTSD than in
      patients having trauma without PTSD, but in the context of trauma-related
      stimuli. P3b amplitude was smaller in patients with PTSD compared to normal
      controls in the context of neutral stimuli. P3wm signals were smaller with
      shorter latencies in patients with PTSD compared to normal controls or medicated
      patients with PTSD. The receiver-operator characteristic (ROC) analysis revealed
      that each P3 component had some potential to accurately classify patients,
      typically using amplitude for at least one lead. In conclusion, differences in P3
      amplitude and latency between patients with PTSD and control patients confirm the
      results of Karl et al and extend our understanding of P3 as a neural correlate of
      working memory. These results further provide guidance on the potential design of
      future clinical trials supporting the development of P3 components as a PTSD
      diagnostic aid.

PMID- 23545247
TI  - Resting parietal electroencephalogram asymmetries and self-reported attentional
      control.
AB  - Research on electroencephalogram (EEG) asymmetries and anxiety proneness has
      recently spread to emotion regulation capabilities. We studied whether
      attentional control (AC), a temperamental construct related to emotional
      regulation, was associated with asymmetrical patterns of resting EEG activity at
      the frontal and parietal regions, reflected not only in the alpha frequency band
      (8-13 Hz) but also in higher bands beta1 (13-20 Hz) and beta2 (20-30 Hz). Self
      reports of AC and trait anxiety, and resting EEG recordings, were obtained from
      58 healthy participants. Correlational analysis showed that lower levels of self
      reported AC were associated with less alpha, beta1, and beta2 powers in the left
      parietal cortex, while no significant relationships were found between the AC and
      EEG oscillations in the prefrontal cortex. The role of the left and right
      parietal lobes in the attentional processes is discussed. 

PMID- 23545248
TI  - Ambient intelligence for monitoring and research in clinical neurophysiology and
      medicine: the MIMERICA* project and prototype.
AB  - Ambient Intelligence (AmI) provides extended but unobtrusive sensing and
      computing devices and ubiquitous networking for human/environment interaction. It
      is a new paradigm in information technology compliant with the international
      Integrating Healthcare Enterprise board (IHE) and eHealth HL7 technological
      standards in the functional integration of biomedical domotics and informatics in
      hospital and home care. AmI allows real-time automatic recording of
      biological/medical information and environmental data. It is extensively
      applicable to patient monitoring, medicine and neuroscience research, which
      require large biomedical data sets; for example, in the study of spontaneous or
      condition-dependent variability or chronobiology. In this respect, AML is
      equivalent to a traditional laboratory for data collection and processing, with
      minimal dedicated equipment, staff, and costs; it benefits from the integration
      of artificial intelligence technology with traditional/innovative sensors to
      monitor clinical or functional parameters. A prototype AmI platform (MIMERICA*)
      has been implemented and is operated in a semi-intensive unit for the vegetative
      and minimally conscious states, to investigate the spontaneous or environment
      related fluctuations of physiological parameters in these conditions.

PMID- 23545249
TI  - A case of schizencephaly has a normal surface EEG but abnormal intracranial EEG:
      epilepsia partialis continua or dystonia?
AB  - Schizencephaly is a congenital malformation of the cerebral hemispheres, with
      communication between the lateral ventricle and the subarachnoid space. Marinelli
      reported that schizencephaly may be associated with continuous involuntary hand
      movements, such as dystonia or epilepsia partialis continua (EPC). We describe a
      young Chinese patient with continuous involuntary movements of the contralateral
      hand affected by schizencephaly. He has a normal scalp electroencephalogram (EEG)
      but abnormal intracranial EEG, with synchronized periodic lateralized
      epileptiform discharges. The results obtained from these EEG investigations and
      the clinical features of the involuntary movements are in favor of a diagnosis of
      secondary EPC. 

PMID- 23545250
TI  - Spatiotemporal analysis of relative convergence of EEGs reveals differences
      between brain dynamics of depressive women and men.
AB  - A new nonlinear technique for analysis of brain dynamics called spatiotemporal
      analysis of relative convergence (STARC) of electroencephalograms (EEGs) is
      introduced, based on the relative convergence of EEGs of different loci. This
      technique shows how many times EEGs of each loci pair converge together, which in
      turn is used as an indicator to determine the different neuronal regions involved
      in performing the same task. A higher STARC value indicates that more regions are
      recruited to perform the same task. The STARC methodology was used to reveal sex
      difference pathophysiology and brain dynamics, using EEG data from 11 male and 11
      female adults with major depressive disorder (MDD). The results show significant
      differences in relative convergences of EEGs of intraleft temporal and frontoleft
      temporal lobes at delta band, between male and female patients. 

PMID- 23545252
TI  - Mutant mice: experimental organisms as materialised models in biomedicine.
AB  - Animal models have received particular attention as key examples of material
      models. In this paper, we argue that the specificities of establishing animal
      models-acknowledging their status as living beings and as epistemological tools
      necessitate a more complex account of animal models as materialised models. This
      becomes particularly evident in animal-based models of diseases that only occur
      in humans: in these cases, the representational relation between animal model and
      human patient needs to be generated and validated. The first part of this paper
      presents an account of how disease-specific animal models are established by
      drawing on the example of transgenic mice models for Alzheimer's disease. We will
      introduce an account of validation that involves a three-fold process including
      (1) from human being to experimental organism; (2) from experimental organism to
      animal model; and (3) from animal model to human patient. This process draws upon
      clinical relevance as much as scientific practices and results in disease
      specific, yet incomplete, animal models. The second part of this paper argues
      that the incompleteness of models can be described in terms of multi-level
      abstractions. We qualify this notion by pointing to different experimental
      techniques and targets of modelling, which give rise to a plurality of models for
      a specific disease. 

PMID- 23545251
TI  - HPV16 E5 and KGFR/FGFR2b interplay in differentiating epithelial cells.
AB  - The E5 oncogenic protein of the human papillomavirus type 16 (HPV16 E5)
      cooperates in epithelial transformation perturbing the behaviour of
      differentiating suprabasal cells. Among the receptor tyrosine kinases deregulated
      by 16E5 expression, the key paracrine mediator of epithelial homeostasis
      keratinocyte growth factor receptor (KGFR/FGFR2b) is altered in its signaling and
      endocytic traffic in undifferentiated keratinocytes expressing 16E5 and it would
      represent a major target of the viral protein in differentiated cells. With the
      aim to specifically address the possible interplay of 16E5 with KGFR/FGFR2b in
      cells already committed to differentiation, we took advantage of an in vitro
      model for forced overexpression or depletion of KGFR in E5 expressing human
      keratinocytes under synchronous waves of differentiation. Quantitative RT-PCR,
      biochemical and immunofluorescence analysis showed that KGFR down-modulation is
      responsible for a E5-mediated decrease of the early differentiation marker K1 and
      that the receptor re-expression as well as triggering of its kinase activity and
      signaling are able to efficiently counteract the impairment of differentiation,
      providing a further demonstration of the tumor-suppressive role of KGFR in the
      new unexplored context of HPV16 E5-mediated carcinogenesis. In addition, KGFR
      induced a ligand-dependent decrease of p63 through a miR-203 independent
      mechanism and this effect was blocked by inhibition of the PI3K/Akt signaling,
      which is the main pathway involved in KGFR-dependent keratinocyte
      differentiation, suggesting that alterations of the KGFR/p63 crosstalk are
      responsible for the impairment of keratinocyte differentiation induced by 16E5
      and that the opposite tumor-suppressive action of KGFR and oncogenic role of E5
      might both involve p63.

PMID- 23545253
TI  - Constitutive and herbivore-induced structural defenses are compromised by
      inbreeding in Solanum carolinense (Solanaceae).
AB  - PREMISE OF THE STUDY: A growing number of studies document effects of inbreeding
      on plant interactions with insect herbivores, including deleterious effects on
      direct and indirect plant defenses. However, our understanding of the specific
      mechanisms mediating such effects remains limited. Here we examine how inbreeding
      affects constitutive and induced expression of structural defenses (spines and
      trichomes) in common horsenettle, Solanum carolinense. * METHODS: Inbred and
      outbred progeny from nine maternal families of horsenettle were assigned to three
      treatments: control, Manduca sexta caterpillar damage, or mechanical damage.
      Numbers of internode spines and the density of abaxial and adaxial trichomes were
      assessed before and after (21 d) damage treatments. Data on internode length,
      flowering time, and total flower production was also collected to explore the
      costs of defense induction. * KEY RESULTS: Inbreeding adversely affected
      constitutive and induced physical/structural defenses: undamaged outbred plants
      produced more abaxial and adaxial leaf trichomes and internode spines than did
      inbred plants. Foliar damage by M. sexta larvae also induced more trichomes (on
      new leaves) and internode spines on outbred plants. Both inbred and outbred
      plants exposed to mechanical or caterpillar damage had shorter internodes than
      did control plants, but inbred damaged plants had longer internodes than did
      outbred damaged plants. Control outbred plants produced significantly more
      flowers than did control inbred plants or damaged plants of either breeding type.
      * CONCLUSIONS: Constitutive and induced structural defenses in horsenettle were
      negatively affected by inbreeding. Reduced flower production and internode length
      on damaged plants compared to controls suggests that defense induction entails
      significant costs.

PMID- 23545254
TI  - Knockdown of HMGA1 inhibits human breast cancer cell growth and metastasis in
      immunodeficient mice.
AB  - The high mobility group A1 gene (HMGA1) has been previously implicated in breast
      carcinogenesis, and is considered an attractive target for therapeutic
      intervention because its expression is virtually absent in normal adult tissue.
      Other studies have shown that knockdown of HMGA1 reduces the tumorigenic
      potential of breast cancer cells in vitro. Therefore, we sought to determine if
      silencing HMGA1 can affect breast cancer development and metastatic progression
      in vivo. We silenced HMGA1 expression in the human breast cancer cell line MDA-MB
      231 using an RNA interference vector, and observed a significant reduction in
      anchorage-independent growth and tumorsphere formation, which respectively
      indicate loss of tumorigenesis and self-renewal ability. Moreover, silencing
      HMGA1 significantly impaired xenograft growth in immunodeficient mice, and while
      control cells metastasized extensively to the lungs and lymph nodes, HMGA1
      silenced cells generated only a few small metastases. Thus, our results show that
      interfering with HMGA1 expression reduces the tumorigenic and metastatic
      potential of breast cancer cells in vivo, and lend further support to
      investigations into targeting HMGA1 as a potential treatment for breast cancer.

PMID- 23545255
TI  - Analysis of ischemic neuronal injury in Cav2.1 channel alpha1 subunit mutant
      mice.
AB  - One of the main instigators leading to cell death and brain damage following
      ischemia is Ca(2+) dysregulation. Neuronal membrane depolarization results in the
      activation of voltage-gated Ca(2+) (CaV) channels and intracellular Ca(2+)
      influx. We investigated the physiological role of the CaV2.1 (P/Q-type) channel
      in ischemic neuronal injury using CaV2.1 channel alpha1 subunit mutant mice,
      rolling Nagoya and leaner mice. The in vivo ischemia model with a complete
      occlusion of the middle cerebral artery showed that the infarct area at 24h was
      significantly smaller in rolling Nagoya (27.1+/-3.5% of total brain volume) and
      leaner (20.1+/-3.5%) mice compared to wild-type (42.9+/-4.5%) mice. In an in
      vitro Ca(2+) imaging study, oxygen-glucose deprivation using a hippocampal slice
      induced a significantly slower rate of increase in intracellular Ca(2+)
      concentration ([Ca(2+)]i) in rolling Nagoya (0.083+/-0.007/min) and leaner
      (0.062+/-0.006/min) mice compared to wild-type (0.105+/-0.008/min) mice. These
      results demonstrate that the mutant CaV2.1 channel in rolling Nagoya and leaner
      mice plays a different protective role in a ([Ca(2+)]i)-dependent manner in
      ischemic models and indicate that CaV2.1 channel blockers may be used
      preventively against ischemic injury.

PMID- 23545256
TI  - Crystal structure of the response regulator spr1814 from Streptococcus pneumoniae
      reveals unique interdomain contacts among NarL family proteins.
AB  - Spr1814 belongs to the NarL/FixJ subfamily of signal transduction response
      regulators (RR), and has been predicted to regulate the neighboring ABC
      transporter, which translocates antibiotic molecules in Streptococcus pneumoniae.
      Here, we report the crystal structure of full-length unphosphorylated spr1814 at
      1.7A resolution. The asymmetric unit contains two spr1814 molecules, which
      display very different conformations. Through comparisons with other RRs
      structures, we concluded that one molecule adopts a general inactive
      conformation, whereas the other molecule adopts an intermediate conformation. The
      superposition of each molecule showed that rotational change of the effector
      domain occurred in intermediate conformational state, implying that domain
      rearrangement could occur upon phosphorylation.

PMID- 23545257
TI  - Structural insights into the coordination of iron by Thermus thermophilus HB8
      ferric binding protein A.
AB  - The ferric binding protein belongs to the substrate-binding protein super-family
      and transports ferric ions across the periplasmic space in gram negative
      bacteria. This process involves the binding and release of ferric ions through
      conformational changes of the ferric binding protein, and the assistance of a
      synergistic anion. Here we report the crystal structure of Thermus thermophilus
      HB8's (TtFbpA) ferric binding protein A in four different forms, which represent
      the apo state (apo-TtFbpA), the carbonate-bound state (TtFbpACO3),and the iron-
      and carbonate-bound state (TtFbpAFeCO3). The ferric ion in TtFbpAFeCO3 is bound
      by three tyrosine residues from TtFbpA and one synergistic carbonate ion.
      Structural comparisons among the three different states reveal the molecular
      mechanisms of iron-binding by TtFbpA. Our results, together with previous studies
      on other bacterial periplasmic ferric binding proteins, provide a complete
      understanding of the structural basis for iron binding and release in the
      periplasm of gram-negative bacteria.

PMID- 23545258
TI  - The blockage of Ras/ERK pathway augments the sensitivity of SphK1 inhibitor SKI
      II in human hepatoma HepG2 cells.
AB  - The treatment of hepatocellular carcinoma (HCC) remains a challenge and the
      future of cancer therapy will incorporate rational combinations directed to
      molecular targets that cooperate to drive critical pro-survival signaling.
      Sphingosine kinase 1 (SphK1) has been shown to regulate various processes
      important for cancer progression. Given the up-regulated expression of SphK1 in
      response to the silence of N-ras and other interactions between Ras/ERK and
      SphK1, it was speculated that combined inhibition of Ras/ERK and SphK1 would
      create enhanced antitumor effects. Experimental results showed that dual blockage
      of N-ras/ERK and SphK1 resulted in enhanced growth inhibitions in human hepatoma
      cells. Similarly, MEK1/2 Inhibitor U0126 potentiated SKI II-induced apoptosis in
      hepatoma HepG2 cells, consistently with the further attenuation of Akt/ERK/NF
      kappaB signaling pathway. It was also shown that the combination of SKI II and
      U0126 further attenuated the migration of hepatoma HepG2 cells via FAK/MLC-2
      signaling pathway. Taken together, the dual inhibition of SphK1 and Ras/ERK
      pathway resulted in enhanced effects, which might be an effective therapeutic
      approach for the treatment of HCC.

PMID- 23545259
TI  - Amyloid fibril formation of peptides derived from the C-terminus of CETP
      modulated by lipids.
AB  - Cholesteryl-ester transfer protein (CETP) is a plasmatic protein involved in
      neutral lipid transfer between lipoproteins. Focusing on the last 12 C-terminus
      residues we have previously shown that mutation D470N promotes a conformational
      change towards a beta-secondary structure. In turn, this modification leads to
      the formation of oligomers and fibrillar structures, which cause cytotoxic
      effects similar to the ones provoked by amyloid peptides. In this study, we
      evaluated the role of specific lipid arrangements on the structure of peptide
      helix-Z (D470N) through the use of thioflavin T fluorescence, peptide bond
      absorbance, circular dichroism and electron microscopy. The results indicate that
      the use of micelles formed with lysophosphatidylcholine and lysophosphatidic acid
      (LPA) under neutral pH induce a conformational transition of peptide helix-Z
      containing a beta-sheet conformation to a native alpha-helix structure, therefore
      avoiding the formation of amyloid fibrils. In contrast, incubation with
      phosphatidic acid does not change the profile for the beta-sheet conformation.
      When the electrostatic charge at the surface of micelles or vesicles is regulated
      through the use of lipids such as phospholipid and LPA, minimal changes and the
      presence of beta-structures were recorded. Mixtures with a positive net charge
      diminished the percentage of beta-structure and the amount of amyloid fibrils.
      Our results suggest that the degree of solvation determined by the presence of a
      free hydroxyl group on lipids such as LPA is a key condition that can modulate
      the secondary structure and the consequent formation of amyloid fibrils in the
      highly flexible C-terminus domain of CETP.

PMID- 23545260
TI  - Identification and characterization of a unique leucine-rich repeat protein
      (LRRC33) that inhibits Toll-like receptor-mediated NF-kappaB activation.
AB  - Toll-like receptors (TLRs) are important initiators in innate immune responses
      against pathogenic microbes such as viruses, intracellular bacteria or parasites.
      Although the innate immune system is designed to fight infectious pathogens,
      excessive activation of TLR signaling may lead to unwarranted inflammation with
      hazardous outcomes. Mechanisms of restraining excessive inflammation and
      controlling homeostasis for innate immunity are the focus of intense study. Here
      we showed that LRRC33, a novel member of leucine-rich repeat (LRR) protein
      family, plays a critical role in desensitizing TLR signaling. LRRC33 is TLR
      homolog that contains 17 putative LRRs in the extracellular region but lacks a
      cytoplasmic Toll/IL-1 receptor (TIR) domain. Expression of LRRC33 appears to be
      ubiquitous with high level of expression found in bone marrow, thymus, liver,
      lung, intestine and spleen. The LRRs of LRRC33 is required for the interaction
      with TLR and its inhibitory effect on NF-kappaB and AP-1 activation as well as
      cytokine production. Our study sheds new insight into the TLR signaling and
      inflammatory response in development and human diseases.

PMID- 23545261
TI  - Salicylic acid resistance is conferred by a novel YRR1 mutation in Saccharomyces
      cerevisiae.
AB  - Yeast cells can extrude intracellular drugs through membrane-associated efflux
      pumps, such as ATP-binding cassette (ABC) transporters and members of the major
      facilitator superfamily. Gene expression of drug efflux pumps is regulated by
      several transcription factors involved in pleiotropic drug resistance (PDR).
      Salicylic acid (SA) possesses weak antifungal activity. Although the excretion
      mechanisms of some antifungal drugs have been revealed, the mechanism of SA
      extrusion remains unclear. To elucidate the mechanism of SA excretion, we
      screened SA-resistant mutants from random mutagenized Saccharomyces cerevisiae
      BY4741 cells. We successfully isolated 60 SA-resistant clones (KinSal001-060).
      KinSal052, one of the strongest SA-resistant clones, also exhibited resistance to
      4-nitroquinoline-1-oxide and cycloheximide, indicating that it acquired the PDR
      phenotype. We identified a novel mutation in YRR1 conferring SA resistance to
      KinSal052. YRR1 encodes a Zn(II)2Cys6-type zinc-finger transcription factor that
      reportedly activates gene expression involved in PDR. Yeast cells carrying the
      yrr1 allele (yrr1-52) activated expression of several efflux pump-encoding genes,
      including YOR1, SNQ2, AZR1, and FLR1. These results suggested that SA resistance
      in KinSal052 is conferred by the overexpression of efflux pumps constitutively
      activated by the mutant form of Yrr1p.

PMID- 23545262
TI  - DAPK1 modulates a curcumin-induced G2/M arrest and apoptosis by regulating STAT3,
      NF-kappaB, and caspase-3 activation.
AB  - Curcumin, an active polyphenol extracted from the perennial herb Curcuma longa,
      controls various molecules involved in tumor cell death. In this study, we found
      that the tumor suppressor death-associated protein kinase 1 (DAPK1) plays a vital
      role in the anti-carcinogenic effects of curcumin. We found that curcumin
      increased DAPK1 expression at the mRNA and protein levels in U251 cells, and that
      the siRNA-mediated knockdown of DAPK1 attenuated the curcumin-induced inhibition
      of STAT3 and NF-kappaB. Moreover, DAPK1 suppression diminished curcumin-induced
      caspase-3 activation. In addition, we confirmed that DAPK1 was required for a
      curcumin-induced G2/M cell cycle arrest and apoptosis. Thus, DAPK1 is involved in
      curcumin-mediated death pathways. Our data suggest novel mechanisms for curcumin
      in cancer therapy.

PMID- 23545263
TI  - Short-term sleep deprivation reinstates memory retrieval in mice: the role of
      corticosterone secretion.
AB  - While the effects of sleep deprivation (SD) on the acquisition and consolidation
      phases of memory have been extensively characterized, its effects on memory
      retrieval remain overlooked. SD alone is a stressor, and stress-activated
      glucocorticoids promote bimodal effects on memory. Because we have recently
      demonstrated that 72h SD impairs memory retrieval in the plus-maze discriminative
      avoidance task (PM-DAT) in mice, this study investigated whether shorter SD
      periods would facilitate retrieval. In Experiment I, the temporal forgetting
      curve of the PM-DAT was determined and an interval between training/testing in
      which retrieval was no longer present was used in all subsequent experiments. In
      Experiments II and III, retrieval performance and corticosterone concentration,
      respectively, were quantified in mice that were sleep deprived for 12 or 24h
      before testing. In Experiments IV and V, the effects of the corticosterone
      synthesis inhibitor metyrapone were evaluated on 12h SD-induced retrieval
      reinstatement and corticosterone concentration enhancement, respectively.
      Experiment VI determined whether pre-test acute administration of exogenous
      corticosterone would mimic the facilitatory effects of 12h SD on retrieval.
      Thirty days after training, mice presented poor performance of the task; however,
      SD for 12h (but not for 24) before testing reinstated memory retrieval. This
      facilitatory effect was accompanied by increased corticosterone concentration,
      abolished by metyrapone, and mimicked by pre-test acute corticosterone
      administration. Collectively, short-term SD can facilitate memory retrieval by
      enhancing corticosterone secretion. This facilitatory effect is abolished by
      longer periods of SD. 

PMID- 23545264
TI  - Effects of pre- or post-processing storage conditions on high-hydrostatic
      pressure inactivation of Vibrio parahaemolyticus and V. vulnificus in oysters.
AB  - The effects of storage conditions on subsequent high-hydrostatic pressure (HHP)
      inactivation of Vibrio parahaemolyticus and Vibrio vulnificus in oysters were
      investigated. Live oysters were inoculated with V. parahaemolyticus or V.
      vulnificus to ca. 7-8 log MPN/g by feeding and stored at varying conditions
      (i.e., 21 or 35  degrees C for 5h, 4 or 10  degrees C for 1 and 2 days and -18 
      degrees C for 2 weeks). Oyster meats were then treated at 225-300 MPa for 2 min
      at 4, 21 or 35  degrees C. HHP at 300 MPa for 2 min achieved a >5-log MPN/g
      reduction of V. parahaemolyticus, completely inactivating V. vulnificus (negative
      by enrichment) in oysters. Treatment temperatures of 4, 21 and 35  degrees C did
      not significantly affect pressure inactivation of V. parahaemolyticus or V.
      vulnificus (P>0.05). Cold storage at -18, 4 and 10  degrees C, prior to HHP,
      decreased V. parahaemolyticus or V. vulnificus populations by 1.5-3.0 log MPN/g,
      but did not increase their sensitivity to subsequent HHP treatments. The effects
      of cold storage after HHP on inactivation of V. parahaemolyticus in oysters were
      also determined. Oysters were inoculated with V. parahaemolyticus and stored at
      21  degrees C for 5h or 4  degrees C for 1 day. Oyster meats were then treated at
      250-300 MPa for 2 min at 21 or 35  degrees C and stored for 15 days in ice or in
      a freezer. V. parahaemolyticus populations in HHP-treated oysters gradually
      decreased during post-HHP ice or frozen storage. A validation study using whole
      shell oysters was conducted to determine whether the presence of oyster shells
      influenced HHP inactivation of V. parahaemolyticus. No appreciable differences in
      inactivation between shucked oyster meat and whole-shell oysters were observed.
      HPP at 300 MPa for 2 min at 21  degrees C, followed by 5-day ice storage or 7-day
      frozen storage, and HPP at 250 MPa for 2 min at 21  degrees C, followed by 10-day
      ice or 7-day frozen storage, completely inactivated V. parahaemolyticus in whole
      shell oysters (>7 log reductions). The combination of HHP at a relatively low
      pressure (e.g., 250 MPa) followed by short-term frozen storage (7 days) could
      potentially be applied by the shellfish industry as a post-harvest process to
      eliminate V. parahaemolyticus in oysters.

PMID- 23545265
TI  - Characterisation of breast implant surfaces and correlation with fibroblast
      adhesion.
AB  - INTRODUCTION: Capsular contracture formation is a common complication following
      breast augmentation surgery. Breast implant shells have either a smooth or a
      textured surface. Smooth surfaces demonstrate a higher incidence of contracture
      formation. The 3-dimensional surface of textured implants is thought to disrupt
      contractile forces and reduce capsular contracture rates. AIM: To investigate the
      interaction of fibroblasts with silicone breast implant surfaces through
      characterization of their unique features. METHOD: Surfaces of smooth and
      textured breast implants were characterized using a confocal laser scanning
      microscope, a microtest 5 kN tensile testing device, and a contact angle
      goniometer. The kinetics of fibroblast interaction with these surfaces was
      further analysed. RESULTS: The textured surfaces were rough, and nodular
      containing high peaks and deep crevasses with roughness (Sa) values in the range
      8.88-18.83 MUm and contact angles between 130 degrees  and 142 degrees . The
      smooth implant surfaces were less rough, more regular and repetitive with 0.06
      0.07 MUm surface roughness, and contact angles between 110.9 degrees  and 111.8
      degrees . The textured surfaces displayed higher bending stiffness than the
      smooth surfaces (0.19 and 0.26 N mm). Significant (p<0.05) numbers of fibroblasts
      were attached to the textured surfaces compared to the smooth surfaces which had
      higher levels of cell adhesion with surface roughness above 8 MUm and contact
      angles above 130 degrees . CONCLUSIONS: In summary, surfaces with arithmetical
      mean deviation of greater roughness and reduced hydrophilicity with high water
      contact angles enhanced cell adhesion. These features aid design of improved
      surfaces, which may help, in prevention of breast capsular formation.

PMID- 23545266
TI  - Disease resistance and health parameters of growth-hormone transgenic and wild
      type coho salmon, Oncorhynchus kisutch.
AB  - To extend previous findings regarding fish health and disease susceptibility of
      growth-enhanced fish, hematological and immunological parameters have been
      compared between growth hormone (GH) transgenic and wild-type non-transgenic coho
      salmon (Oncorhynchus kisutch). Compared to non-transgenic coho salmon, transgenic
      fish had significantly higher hematocrit (Hct), hemoglobin (Hb), mean cellular
      hemoglobin (MCH), mean cellular volume (MCV), and erythrocyte numbers, and lower
      white cell numbers. In addition, resistance to the bacterial pathogen Aeromonas
      salmonicida (causal agent of furunculosis) has been assessed between the strains.
      Higher susceptibility of transgenic fish to this disease challenge was observed
      in two separate year classes of fish. The present findings provide fundamental
      knowledge of the disease resistance on GH enhanced transgenic coho salmon, which
      is of importance for assessing the fitness of transgenic strains for
      environmental risk assessments, and for improving our understanding effects of
      growth modification on basic immune functions.

PMID- 23545267
TI  - The sensitivity of the calculation of DeltaV to vehicle and impact parameters.
AB  - DeltaV is frequently used to describe collision severity, and is often used by
      accident investigators to estimate speeds of vehicles prior to a collision, and
      by researchers looking for correlations between severity and outcome. This study
      identifies how DeltaV varies over a wide range of input uncertainties allowing
      the direct comparison of different methods of input data collection in terms of
      their effect on uncertainty in the calculation of DeltaV. Software was developed
      to implement this sensitivity analysis and was validated against examples
      presented in the CRASH3 manual. The findings are therefore representative of, and
      relevant to, commercially available tools such as CRASH3 and AIDamage. It is
      possible to measure the vehicle and collision parameters with sufficient accuracy
      to determine DeltaV to a level of precision that is useful to predict occupant
      fatality. In many cases, DeltaV is largely insensitive to the input parameter and
      category values or values determined from photographs may be used. A vehicle
      specific value of the stiffness parameter B should be used. Direct measurement of
      crush measurements and vehicle mass (including the best estimates of fluid loss)
      should be used. Similarly the mass of occupants and cargo should be measured
      directly rather than estimated from 50th centile values. Calculation of DeltaV is
      sensitive to PDOF which should be measured with a precision of better than +/-6
      degrees .

PMID- 23545268
TI  - Pregnant driver-associated motor vehicle crashes in North Carolina, 2001-2008.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of maternal injury
      related mortality during pregnancy in the United States, yet pregnant women
      remain an understudied population in motor vehicle safety research. METHODS: We
      estimated the risk of being a pregnant driver in a crash among 878,546 pregnant
      women, 16-46 years, who reached the 20th week of pregnancy in North Carolina (NC)
      from 2001 to 2008. We also examined the circumstances surrounding the crash
      events. Pregnant drivers in crashes were identified by probabilistic linkage of
      live birth and fetal death records and state motor vehicle crash reports.
      RESULTS: During the 8-year study period, the estimated risk of being a driver in
      a crash was 12.6 per 1000 pregnant women. Pregnant women at highest risk of being
      drivers in serious crashes were 18-24 years old (4.5 per 1000; 95% confidence
      interval, CI,4.3, 4.7), non-Hispanic black (4.8 per 1000; 95% CI=4.5, 5.1), had
      high school diplomas only (4.5 per 1000; 95% CI=4.2, 4.7) or some college (4.1
      per 1000; 95% CI=3.9, 4.4), were unmarried (4.7 per 1000; 95% CI=4.4, 4.9), or
      tobacco users (4.5 per 1000; 95% CI=4.1, 5.0). A high proportion of crashes
      occurred between 20 and 27 weeks of pregnancy (45%) and a lower proportion of
      crashes involved unbelted pregnant drivers (1%) or airbag deployment (10%). Forty
      percent of crashes resulted in driver injuries. CONCLUSIONS: NC has a relatively
      high pregnant driver crash risk among the four U.S. states that have linked vital
      records and crash reports to examine pregnancy-associated crashes. Crash risks
      were especially elevated among pregnant women who were young, non-Hispanic black,
      unmarried, or used tobacco. Additional research is needed to quantify pregnant
      women's driving frequency and patterns.

PMID- 23545269
TI  - Public satisfaction as a measure of health system performance: a study of nine
      countries in the former Soviet Union.
AB  - Measurement of health system performance increasingly includes the views of
      healthcare users, yet little research has focussed on general population
      satisfaction with health systems. This study is the first to examine public
      satisfaction with health systems in the former Soviet Union (fSU). Data were
      derived from two related studies conducted in 2001 and 2010 in nine fSU
      countries, using nationally representative cross-sectional surveys. The
      prevalence of health system satisfaction in each country was compared for 2001
      and 2010. Patterns of satisfaction were further examined by comparing
      satisfaction with the health system and other parts of the public sector, and the
      views of health care users and non-users. Potential determinants of population
      satisfaction were explored using logistic regression. For all countries combined,
      the level of satisfaction with health systems increased from 19.4% in 2001 to
      40.6% in 2010, but varied considerably by country. Changes in satisfaction with
      the health system were similar to changes with the public sector, and non-users
      of healthcare were slightly more likely to report satisfaction than users.
      Characteristics associated with higher satisfaction include younger age, lower
      education, higher economic status, rural residency, better health status, and
      higher levels of political trust. Our results suggest that satisfaction can
      provide useful insight into public opinion on health system performance,
      particularly when used in conjunction with other subjective measures of
      satisfaction with government performance. 

PMID- 23545270
TI  - Understanding stress-effects in the brain via transcriptional signal transduction
      pathways.
AB  - Glucocorticoid hormones exert crucial effects on the brain in relation to
      physiology, endocrine regulation, mood and cognition. Their two receptor types,
      glucocorticoid and mineralocorticoid receptors (GR and MR), are members of the
      nuclear receptor superfamily and act in large measure as transcription factors.
      The outcome of MR/GR action on the genome depends on interaction with members
      from different protein families, which are of crucial importance for cross-talk
      with other neuronal and hormonal signals that impinge on the glucocorticoid
      sensitive circuitry. Relevant interacting proteins include other transcription
      factors that may either tether the receptor to the DNA, or that bind in the
      vicinity of GR and MR to tune the transcriptional response. In addition,
      transcriptional coregulator proteins constitute the actual signal transduction
      pathway to the transcription machinery. We review the current evidence for
      involvement of individual coregulators in GR-dependent effects on stress
      responses, and learning and memory. We discuss the use of in vitro and in silico
      tools to predict those coregulators that are of importance for particular brain
      processes. Finally, we discuss the potential of selective receptor modulators
      that may only allow a subset of all interactions, thus allowing more selective
      targeting of glucocorticoid-dependent processes in the brain.

PMID- 23545271
TI  - Neuroprotection induced by N-acetylcysteine against cytosolic glutathione
      depletion-induced Ca2+ influx in dorsal root ganglion neurons of mice: role of
      TRPV1 channels.
AB  - Glutathione (GSH) and N-acetylcysteine (NAC) are thiol-containing antioxidants,
      and also act through a direct reaction with free radicals. Transient receptor
      potential vanilloid 1 (TRPV1) is the principal transduction channel serving as a
      polymodal detector. Despite the importance of oxidative stress in pain
      sensitivity, its role in TRPV1 modulation is poorly understood. NAC may also have
      a regulator role on TRPV1 channel activity in the dorsal root ganglion (DRG)
      neuron. Therefore, we tested the effects of GSH and NAC on TRPV1 channel current,
      Ca(2+) influx, oxidative stress and caspase activity in the DRG of mice. DRG
      neurons were freshly isolated from mice and the neurons were incubated for 6 and
      24h with buthionine sulfoximine (BSO). Pretreatment of cultured DRG neurons with
      NAC, results in a protection against oxidative damages. This neuroprotection is
      associated with the attenuation of a Ca(2+) influx triggered by oxidative agents
      such as H2O2, 5,5'-dithiobis-(2-nitrobenzoic acid) and GSH depletion via BSO.
      Here, we demonstrate the contribution of cytosolic factors (related to thiol
      group depletion) on the activation of TRPV1 channels in this mechanism. TRPV1
      channels are activated by various agents including capsaicin (CAP), the pungent
      component of hot chili peppers, and are blocked by capsazepine. An oxidative
      environment also increased CAP-evoked TRPV1 currents in the neurons. When NAC and
      GSH were included in the patch pipette as well as extracellularly in the chamber,
      TRPV1 channels were not activated by CAP and H2O2. TRPV1 inhibitors, 2-aminoethyl
      diphenylborinate and N-(p-amylcinnamoyl)anthranilic acid strongly reduced BSO
      induced oxidative toxicity and Ca(2+) influx, in a manner similar to pretreatment
      with NAC and GSH. Caspase-3 and -9 activities of all groups were not changed by
      the agonists or antagonists. In conclusion, in our experimental model, TRPV1
      channels are involved in the oxidative stress-induced neuronal death, and
      negative modulation of this channel activity by GSH and NAC pretreatment may
      account for their neuroprotective activity against oxidative stress.

PMID- 23545273
TI  - Hygiene and the cytokine jungle in Brazil.

PMID- 23545272
TI  - A grey mullet enzyme displaying both lipase and phospholipase activities:
      purification and characterization.
AB  - A lipase from the golden grey mullet viscera was purified to homogeneity by
      ammonium sulphate precipitation, gel filtration, anionic and cation exchange
      chromatographies. The pure enzyme tentatively named grey mullet digestive lipase
      (GmDL) is a monomer having a molecular mass of about 35 kDa, as determined by SDS
      PAGE analysis. No similarity was found between the NH2-terminal amino acid
      residues of GmDL and those of other known digestive lipases. GmDL is a serine
      enzyme, like all known lipases from different origins. Interestingly, GmDL has
      not only lipase activity but also a phospholipase activity which requires the
      presence of Ca(2+) and bile salts. Specific activities of 64 U/mg, 55 U/mg and 63
      U/mg were measured using tributyrin, olive oil emulsion or phosphatidylcholine as
      substrate, respectively at pH 8 and at 50 degrees C. GmDL is therefore a thermo
      active enzyme as compared to other fish lipases studied so far. It is worth to
      notice that grey mullet lipase was active in the presence of salt concentrations
      as high as 0.8M.

PMID- 23545274
TI  - Comparative outcomes of leukotriene receptor antagonists and long-acting beta
      agonists as add-on therapy in asthmatic patients: a population-based study.
AB  - BACKGROUND: Recent evidence suggests that the use of leukotriene receptor
      antagonists (LTRAs) in addition to inhaled corticosteroids (ICSs) in asthmatic
      patients provides comparable benefits to the addition of long-acting beta
      agonists (LABAs) to ICSs. OBJECTIVE: We sought to compare, in a unified
      framework, adherence, outcomes, and costs associated with ICS+LTRA versus
      ICS+LABA as step-up therapies for asthma. METHODS: Using the administrative
      databases of British Columbia, Canada (years 1997-2007), we created a propensity
      score-matched sample of asthmatic patients (12-45 years old) receiving ICS+LTRA
      therapy versus ICS+LABA therapy after a period of monotherapy with an ICS. We
      compared the outcomes using 2 analyses: an intention-to-treat (ITT) analysis that
      followed subjects for a fixed period of 2 years and an uninterrupted treatment
      analysis that followed subjects for as long as they continuously dispensed their
      index medications. RESULTS: The matched cohort consisted of 1032 subjects in each
      group (mean age at entry, 27.4 years; 52.5% female). Adherence, which was defined
      as the proportion of days covered, was higher in the ICS+LABA group compared with
      the ICS+LTRA group. In both the ITT and uninterrupted treatment analyses, use of
      ICS+LTRA therapy was associated with more asthma-related outpatient visits,
      asthma-related medication dispensations, and dispensation of reliever
      medications. Dispensation of oral corticosteroids and rate of asthma
      exacerbations were higher in the ICS+LTRA group in the uninterrupted treatment
      analysis but not in the ITT analysis. CONCLUSIONS: In a real-world clinical
      setting subjects were more adherent to ICS+LABA therapy than ICS+LTRA therapy.
      ICS+LABA therapy seems to be more effective than ICS+LTRA therapy in the
      management of asthma, regardless of adherence.

PMID- 23545275
TI  - A novel splice variant of FcgammaRIIa: a risk factor for anaphylaxis in patients
      with hypogammaglobulinemia.
AB  - BACKGROUND: Our index case was a patient with common variable immunodeficiency
      (CVID). She had anaphylactoid reactions on administration of intravenous
      immunoglobulin (IVIg) associated with the presence of IgG antibodies against IgA.
      OBJECTIVE: We sought to determine the role of Fcgamma receptor (FcgammaR) IIa in
      IVIg-induced anaphylactoid reactions. METHODS: Neutrophils and PBMCs were
      isolated from healthy subjects and IVIg-treated patients. FcgammaRIIa mRNA and
      DNA were analyzed by using real-time PCR and sequencing. IgG-mediated elastase
      release and intracellular Ca(2+) mobilization were determined in neutrophils and
      transfected cell lines, respectively. RESULTS: A novel splice variant of
      FcgammaRIIa containing an expressed cryptic exon 6* (FcgammaRIIa(exon6*)) was
      identified in our index patient. This exon is normally spliced out of all
      FcgammaRII isoforms, except the inhibitory FcgammaRIIb1. Compared with healthy
      control subjects, the heterozygous FCGR2A(c.742+871A>G) mutation was more
      frequent in patients with CVID (n = 53, P < .013). Expression in patients with
      CVID was associated with anaphylaxis on IVIg infusion (P = .002). On screening of
      additional IVIg-treated patient cohorts, we identified 6 FCGR2A(c.742+871A>G)
      allele-positive patients with Kawasaki disease (n = 208) and 1 patient with
      idiopathic thrombocytopenia (n = 93). None had adverse reactions to IVIg.
      Moreover, FcgammaRIIa(exon6*) was also demonstrated in asymptomatic family
      members. Functional studies in primary cells and transfected murine cells
      demonstrated enhanced cellular activation by FcgammaRIIa(exon6*) compared with
      its native form, as shown by increased elastase release and intracellular calcium
      mobilization. CONCLUSION: A novel splice variant, FcgammaRIIa(exon6*), was
      characterized as a low-frequency allele, coding for a gain-of-function receptor
      for IgG. In the presence of immune complexes, FcgammaRIIa(exon6*) can contribute
      to anaphylaxis in patients with CVID.

PMID- 23545276
TI  - Significant cost savings achieved by in-sourcing urine drug testing for
      monitoring medication compliance in pain management.
AB  - INTRODUCTION: Reference laboratory testing can represent a significant component
      of the laboratory budget. Therefore, most laboratories continually reassess the
      feasibility of in-sourcing various tests. We describe the transfer of urine drug
      testing performed for monitoring medication compliance in pain management from a
      reference laboratory into an academic clinical laboratory. METHODS: The process
      of implementing of both screening immunoassays and confirmatory LC-MS/MS testing
      and the associated cost savings is outlined. RESULTS: The initial proposal for in
      sourcing this testing, which included the tests to be in-sourced, resources
      required, estimated cost savings and timeline for implementation, was approved in
      January 2009. All proposed testing was implemented by March 2011. CONCLUSIONS:
      Keys to the successful implementation included budgeting adequate resources and
      developing a realistic timeline, incorporating the changes with the highest
      budget impact first. We were able to in-source testing in 27 months and save the
      laboratory approximately $1 million in the first 3 year.

PMID- 23545277
TI  - A clinical PCR fragment analysis assay for TA repeat sizing in the UGT1A1
      promoter region.
AB  - BACKGROUND: A genetic TA repeat length polymorphism in the UGT1A1 promoter has
      been shown to affect UDP-glucuronosyltyransferase (UGT1A1) expression levels with
      significant clinical implications. The presence of 7 TA repeats has been
      associated with lowered UGT1A1 expression and the mild hyperbilinrubinemia
      manifested in Gilbert's syndrome. Furthermore, cancer patients carrying this
      variant exhibit irinotecan-related toxicity and require lower doses of this
      chemotherapeutic agent compared to patients carrying the 6 TA repeat allele. This
      polymorphism is very common and, therefore, necessitates the development of
      reliable means of detecting it in the clinical laboratory to deliver better
      personalized therapy regimens. METHODS: We used 45 whole blood samples from
      patients previously tested with the FDA-approved Invader UGT1A1 assay (Hologic,
      Madison, WI) to assess extraction method, analytical sensitivity, accuracy and
      precision of this assay. In addition, cell line controls were used to test for
      the common and rare alleles of this polymorphism. The assay was based on PCR
      amplification and capillary electrophoresis for accurate sizing of the TA repeat
      copy number. RESULTS: All samples tested and controls gave the expected results.
      CONCLUSIONS: We have developed and validated a simple and sensitive PCR fragment
      analysis assay for accurately determining TA repeat length in the UGT1A1
      promoter. At our medical center, this testing is used primarily for guiding
      irinotecan dosing decisions for our cancer patients.

PMID- 23545278
TI  - Utility of neut-X, neut-Y and neut-Z parameters for rapidly assessing sepsis in
      tumor patients.
AB  - BACKGROUND: The Sysmex XE-5000 hematology analyzer evaluates toxic granulation
      and the nuclear maturity of toxic granulation neutrophils via the parameters neut
      X and neut-Y. This study investigated whether neut-X and neut-Y could facilitate
      the auxiliary diagnosis of sepsis. METHODS: Blood samples were collected from 113
      patients with tumors and 130 healthy individuals to detect neut-X, neut-Y, and C
      reactive protein (CRP) values. Then, we created a new parameter, neut-Z, the
      vector sum of neut-X and neut-Y. Furthermore, we assessed procalcitonin (PCT)
      concentrations in patients with sepsis and compared the values with those for
      neut-X, neut-Y, and neut-Z. RESULTS: Neut-X, neut-Y, neut-Z, and CRP values were
      significantly higher in the sepsis group than in the non-sepsis and healthy
      groups. The ROC-AUCs for neut-X, neut-Y, neut-Z, and CRP for a diagnosis of
      sepsis were 0.87 (sensitivity 82%, specificity 79%), 0.87 (78 and 94%,
      respectively), 0.91 (82 and 88%, respectively), and 0.95 (96 and 89%,
      respectively), respectively. Additionally, neut-X, neut-Y, and neut-Z were
      correlated with CRP and PCT levels. CONCLUSIONS: Neut-X and neut-Y can be used as
      rapid and simple auxiliary indicators in the diagnosis of sepsis in patients with
      tumors, and neut-Z appears to display better performance than its 2 components.

PMID- 23545279
TI  - Efficacy and safety of weekly nab-paclitaxel plus carboplatin in patients with
      advanced non-small cell lung cancer.
AB  - PURPOSE: In a large multicenter international phase III study (CA031) of nab
      paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C)
      vs solvent-based paclitaxel (sb-P) + C, conducted in 6 countries including Japan,
      nab-PC produced significantly higher overall response rate (ORR), primary end
      point compared with sb-PC, and acceptable safety profile. The aim of this
      analysis was to evaluate the efficacy and tolerability of nab-PC vs sb-PC in
      Japanese patients with advanced non-small-cell lung cancer (NSCLC) who were
      enrolled in the CA031 study. PATIENTS AND METHODS: In the CA031 study, a total of
      1052 patients were randomized to receive either nab-P 100 mg/m(2) weekly or sb-P
      200 mg/m(2) every 3 weeks both in combination with C at area under the
      concentration-time curve (AUC) = 6 on day 1 of each 3-week cycle. This analysis
      included 149 Japanese patients with previously untreated stage IIIB or IV NSCLC.
      RESULTS: The baseline and histologic characteristics of patients were well
      balanced between the two arms. ORR was higher with nab-PC vs sb-PC (35% vs 27%;
      response rate ratio = 1.318). Progression-free survival (median 6.9 vs 5.6
      months; hazard ratio [HR] = 0.845) and overall survival (median 16.7 vs 15.9
      months; HR = 0.930) were better with nab-PC vs sb-PC. Of the grade >=3 treatment
      related adverse events, anemia and thrombocytopenia were more common in nab-PC
      arm, but sensory neuropathy was less common. CONCLUSION: The nab-PC treatment
      yielded promising results regarding the efficacy endpoint, and it was generally
      well tolerated as first-line therapy for Japanese patients with advanced NSCLC.

PMID- 23545280
TI  - An evaluation of memory accuracy in food hoarding marsh tits Poecile palustris-
      how accurate are they compared to humans?
AB  - Laboratory studies of scatter hoarding birds have become a model system for
      spatial memory studies. Considering that such birds are known to have a good
      spatial memory, recovery success in lab studies seems low. In parids (titmice and
      chickadees) typically ranging between 25 and 60% if five seeds are cached in 50
      128 available caching sites. Since these birds store many thousands of food items
      in nature in one autumn one might expect that they should easily retrieve five
      seeds in a laboratory where they know the environment with its caching sites in
      detail. We designed a laboratory set up to be as similar as possible with
      previous studies and trained wild caught marsh tits Poecile palustris to store
      and retrieve in this set up. Our results agree closely with earlier studies, of
      the first ten looks around 40% were correct when the birds had stored five seeds
      in 100 available sites both 5 and 24h after storing. The cumulative success curve
      suggests high success during the first 15 looks where after it declines. Humans
      performed much better, in the first five looks most subjects were 100% correct.
      We discuss possible reasons for why the birds were not doing better. 

PMID- 23545281
TI  - Antihypertensives suppress the emergence of fluoroquinolone-resistant mutants in
      pneumococci: an in vitro study.
AB  - BACKGROUND: The antihypertensives reserpine and verapamil are also inhibitors of
      pneumococcal efflux pumps. We addressed the following questions: (i) Do verapamil
      and reserpine influence the mutation ratio of pneumococci in the presence of
      ciprofloxacin? (ii) At which concentrations does this occur? (iii) Is this
      limited to isolates with efflux phenotype? METHODS: 14 clinical isolates, nested
      in 6 genetically similar clusters, were used, 7 strains with efflux and 7
      without. The mutation ratio in the presence of ciprofloxacin (3 * MIC) and
      increasing concentrations of reserpine and verapamil was determined and the
      quinolone-resistance determining regions (QRDR) of selected mutants were
      sequenced. Analysis of the efficacy was performed using a mixed linear model,
      supported by descriptive statistics. RESULTS: Reserpine and verapamil reduced the
      mutation ratio of QRDR in the presence of ciprofloxacin with the required
      concentration for a reduction >= 50% of 1mg/l for reserpine and 50mg/l for
      verapamil. The mutation prevention effect is not limited to, but is more
      pronounced in efflux positive phenotypes. CONCLUSION: Reserpine and verapamil can
      prevent the selection of ciprofloxacin resistant isolates by reduction of the
      mutation ratio, particularly in strain with an efflux phenotype. However, the
      required concentrations are too toxic for clinical use.

PMID- 23545282
TI  - [Follow-up of children conceived by assisted reproductive technologies].
AB  - Since the birth of the first baby conceived by in vitro fertilization (IVF) 30
      years ago (Louise Brown in 1978), there has been a rapid and constant increase in
      the number of couples using assisted reproductive technologies (ART). Around four
      million of children have been born from couples experiencing fertility problems,
      through the use of ART, comprising roughly 2-3 % of all births in Europe and U.S.
      That highlights that these modes of fertilization are now well assumed by our
      societies. However, several questions on health of these children remain to be
      elucidated. As evoked in this review, even if methodological limitations exist,
      numerous studies have reported increased risks of birth defects, like
      prematurity, foetal hypotrophy, neonatal complications, congenital malformations
      and epigenetic diseases among ART-conceived children as compared to naturally
      conceived children. Nowadays, it is difficult to determine if these increased
      risks found in ART infants are a consequence of the ART procedures or are
      inherent to the infertility problems per se. However, absolute risks remain
      moderate and reassuring as well as the data on follow-up into infancy and early
      childhood. Nevertheless, because the effects may occur at the adulthood, there is
      a need for long-term follow-up of children born after ART.

PMID- 23545283
TI  - Dynamic state allocation for MEG source reconstruction.
AB  - Our understanding of the dynamics of neuronal activity in the human brain remains
      limited, due in part to a lack of adequate methods for reconstructing neuronal
      activity from noninvasive electrophysiological data. Here, we present a novel
      adaptive time-varying approach to source reconstruction that can be applied to
      magnetoencephalography (MEG) and electroencephalography (EEG) data. The method is
      underpinned by a Hidden Markov Model (HMM), which infers the points in time when
      particular states re-occur in the sensor space data. HMM inference finds short
      lived states on the scale of 100ms. Intriguingly, this is on the same timescale
      as EEG microstates. The resulting state time courses can be used to intelligently
      pool data over these distinct and short-lived periods in time. This is used to
      compute time-varying data covariance matrices for use in beamforming, resulting
      in a source reconstruction approach that can tune its spatial filtering
      properties to those required at different points in time. Proof of principle is
      demonstrated with simulated data, and we demonstrate improvements when the method
      is applied to MEG.

PMID- 23545284
TI  - Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a
      randomized phase 2 study of neoadjuvant combined modality chemoradiation for
      distal rectal cancer.
AB  - PURPOSE: To assess the efficacy of 2 different approaches to neoadjuvant
      chemoradiation for distal rectal cancers. METHODS AND MATERIALS: One hundred six
      patients with T3/T4 distal rectal cancers were randomized in a phase 2 study.
      Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5
      FU), 225 mg/m(2) per day, 7 days per week plus pelvic hyperfractionated radiation
      (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4
      cancers (Arm 1), or CVI of 5-FU, 225 mg/m(2) per day, Monday to Friday, plus
      irinotecan, 50 mg/m(2) once weekly * 4, plus pelvic radiation therapy (RT), 45 Gy
      at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2).
      Surgery was performed 4 to 10 weeks later. RESULTS: All eligible patients (n=103)
      are included in this analysis; 2 ineligible patients were excluded, and 1 patient
      withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four
      patients did not undergo surgery for either disease progression or patient
      refusal, and 1 patient died during induction chemotherapy. The median time of
      follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological
      complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional
      recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates
      were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1
      and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and
      1 second primary occurred in Arm 2. CONCLUSIONS: High rates of disease-specific
      survival were seen in each arm. Overall survival appears affected by the
      development of unrelated second cancers. The high pCR rates with 5-FU and higher
      dose radiation in T4 cancers provide opportunity for increased R0 resections and
      improved survival.

PMID- 23545285
TI  - Macrophage migration inhibitory factor of Sciaenops ocellatus regulates immune
      cell trafficking and is involved in pathogen-induced immune response.
AB  - Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine
      involved in immunoregulation and inflammation. In this study, we examined the
      expression and biological function of a MIF, SoMIF, from red drum Sciaenops
      ocellatus. SoMIF is composed of 115 residues and shares 85-99% overall sequence
      identities with the MIF of a number of teleost. SoMIF expression was detected in
      a wide range of tissues and upregulated by bacterial and viral infection in a
      time-dependent manner. In head kidney (HK) leukocytes, pathogen infection induced
      SoMIF expression, and the expressed SoMIF was secreted into the extracellular
      milieu. Recombinant SoMIF (rSoMIF) purified from Escherichia coli inhibited the
      migration of both HK monocytes and lymphocytes, and this inhibitory effect was
      abolished by the presence of anti-rSoMIF antibodies. When rSoMIF was administered
      into red drum, it stimulated the production of reactive oxygen species in HK
      monocytes both in the presence and absence of pathogen infection. In vivo
      infection study showed that compared to untreated fish, fish pre-treated with
      rSoMIF before bacterial infection exhibited significantly lower bacterial loads
      in blood, kidney, spleen, and liver. Taken together, these results indicate that
      SoMIF is a secreted protein that regulates immune cell trafficking and is
      involved in pathogen-induced immune response.

PMID- 23545286
TI  - The Drosophila clotting system and its messages for mammals.
AB  - Drosophila has been increasingly used as a model to study hemolymph clotting.
      Proteomics and bioinformatics identified candidate clotting-factors, several of
      which were tested using genetics. Mutants and lines with reduced expression of
      clotting-factors show subtle effects after wounding, indicating that sealing
      wounds may rely on redundant mechanisms. More striking effects are observed after
      infection, in particular when a natural infection model involving
      entomopathogenic nematodes is used. When translated into mammalian models these
      results reveal that mammalian blood clots serve a similar immune function, thus
      providing a new example of the usefulness of studying invertebrate models. 

PMID- 23545287
TI  - The performance of silk scaffolds in a rat model of augmentation cystoplasty.
AB  - The diverse processing plasticity of silk-based biomaterials offers a versatile
      platform for understanding the impact of structural and mechanical matrix
      properties on bladder regenerative processes. Three distinct groups of 3-D
      matrices were fabricated from aqueous solutions of Bombyx mori silk fibroin
      either by a gel spinning technique (GS1 and GS2 groups) or a solvent-casting/salt
      leaching method in combination with silk film casting (FF group). SEM analyses
      revealed that GS1 matrices consisted of smooth, compact multi-laminates of
      parallel-oriented silk fibers while GS2 scaffolds were composed of porous (pore
      size range, 5-50 MUm) lamellar-like sheets buttressed by a dense outer layer. Bi
      layer FF scaffolds were comprised of porous foams (pore size, ~400 MUm) fused on
      their external face with a homogenous, nonporous silk film. Silk groups and small
      intestinal submucosa (SIS) matrices were evaluated in a rat model of augmentation
      cystoplasty for 10 weeks of implantation and compared to cystotomy controls.
      Gross tissue evaluations revealed the presence of intra-luminal stones in all
      experimental groups. The incidence and size of urinary calculi was the highest in
      animals implanted with gel spun silk matrices and SIS with frequencies >=57% and
      stone diameters of 3-4 mm. In contrast, rats augmented with FF scaffolds
      displayed substantially lower rates (20%) and stone size (2 mm), similar to the
      levels observed in controls (13%, 2 mm). Histological (hematoxylin and eosin,
      Masson's trichrome) and immunohistochemical (IHC) analyses showed comparable
      extents of smooth muscle regeneration and contractile protein (alpha-smooth
      muscle actin and SM22alpha) expression within defect sites supported by all
      matrix groups similar to controls. Parallel evaluations demonstrated the
      formation of a transitional, multi-layered urothelium with prominent uroplakin
      and p63 protein expression in all experimental groups. De novo innervation and
      vascularization processes were evident in all regenerated tissues indicated by
      Fox3-positive neuronal cells and vessels lined with CD31 expressing endothelial
      cells. In comparison to other biomaterial groups, cystometric analyses at 10
      weeks post-op revealed that animals implanted with the FF matrix configuration
      displayed superior urodynamic characteristics including compliance, functional
      capacity, as well as spontaneous non voiding contractions consistent with control
      levels. Our data demonstrate that variations in scaffold processing techniques
      can influence the in vivo functional performance of silk matrices in bladder
      reconstructive procedures.

PMID- 23545288
TI  - Targeting delivery of saquinavir to the brain using 83-14 monoclonal antibody
      grafted solid lipid nanoparticles.
AB  - 83-14 monoclonal antibody (MAb) was modified on solid lipid nanoparticles (SLNs)
      to improve the brain-targeting delivery of saquinavir (SQV). The endocytosis of
      83-14 MAb-grafted SQV-loaded SLNs (83-14 MAb/SQV-SLNs) into human brain
      microvasscular endothelial cells (HBMECs) was studied by staining cell nuclei,
      insulin receptors, and drug carriers. An increase in the weight fraction of
      palmitic acid in lipid core enhanced the particle size, absolute value of zeta
      potential, and viability of HBMECs and reduced the entrapment efficiency and
      release rate of SQV. In addition, an increase in the weight fraction of poloxamer
      407 in surfactant layer reduced the particle size, absolute value of zeta
      potential, phagocytosis by RAW246.7 cells, permeability across the blood-brain
      barrier (BBB), and uptake by HBMECs and enhanced the viability of HBMECs.
      Moreover, an increase in the concentration of surface 83-14 MAb enhanced the
      percentage of surface nitrogen, permeability across the BBB, and uptake by HBMECs
      and did not significantly vary the viability of HBMECs and phagocytosis by
      RAW264.7 cells. 83-14 MAb/SQV-SLNs can ameliorate the bioavailability
      characteristics of SQV, inhibit the lymphatic particle uptake, and promote the
      transport of SQV into brain endothelia.

PMID- 23545289
TI  - Cell penetration and cell-selective drug delivery using alpha-helix peptides
      conjugated with gold nanoparticles.
AB  - Cell penetrating peptides (CPPs) have been developed as vectors for molecular
      delivery into various cells for use in drug delivery, gene therapy and cancer
      treatment by their property transporting various molecules into cytoplasm. CPPs
      with high internalization, cell specificity, and low cytotoxicity have been
      considered to increase the applicability for cell engineering. Gold nanospheres
      (GNSs) are a useful tool for molecular imaging, because they are non-cytotoxic
      and have high solubility, ease of synthesis and excellent light scattering
      property. Here, we investigated the cell penetrability using alpha-helix peptides
      of 17-amino acids conjugated to gold nanospheres (P-GNS). Depending on the
      peptide sequence had the different cell penetrating (CP) activity for three kinds
      of cell lines. P-GNS showed low cytotoxicity and high selectivity against three
      cell types, despite just one amino acid difference between the peptide. We
      studied the cytotoxic activity of an anti-cancer drug doxorubicin (DOX)
      conjugated to the P-GNS. They showed different cytotoxicity against the three
      cell lines, depending on the peptide sequence, with a higher efficiency than free
      DOX at the same concentration. The cytotoxicity by DOX was correlated with the CP
      activity of the peptides against the three cell lines. These results demonstrated
      that P-GNS would be a useful tool for the development of a new cell-selective
      drug delivery system.

PMID- 23545290
TI  - Functional recovery of urethra by plasmid DNA-loaded injectable agent for the
      treatment of urinary incontinence.
AB  - Stress urinary incontinence (SUI) is an embarrassing problem affecting a large
      number of women and interfering with their quality of life. The injury or
      weakness of urethral supporting tissues by childbirth and aging has been
      considered as key factors in the development of the SUI. In this study, plasmid
      DNA (pDNA; encoding for bFGF) complex-loaded poly(DL-lactic-co-glycolic acid)
      (PLGA)/Pluronic F127 mixture dispersed with polycaprolactone (PCL) microspheres
      was prepared as an injectable bioactive bulking agent that may provide bulking
      effect (by PCL microspheres) and allow stimulation of the defect tissues around
      urethra (by synthesis of bFGF from cells or tissues transfected by the pDNA
      complex) for the effective treatment of SUI. From in vitro experiments, the pDNA
      complex incorporated in the bulking agent was released in a sustained manner over
      84 days (>=80% of the initial loading amount). The pDNA complex was effectively
      transfected into fibroblasts and the cells were continuously producing the target
      protein, bFGF. From the in vivo study using hairless mice and Sprague-Dawley
      rats, it was confirmed that the pDNA complex released from the bulking agent is
      transfected into surrounding cells/tissue, and the cells/tissues synthesize
      sufficient bFGF to regenerate smooth muscle with biological function around the
      urethra. Basis on these results, the pDNA (encoding for bFGF) complex-loaded
      PLGA/Pluronic F127 mixture dispersed with PCL microspheres can be a promising
      bioactive bulking agent system for the fundamental cure of SUI.

PMID- 23545291
TI  - Forced-convective vitrification with liquid cryogens.
AB  - Cell cryopreservation by vitrification generally requires using vitrification
      solutions with high concentrations of cryoprotectants (CPAs), which are toxic and
      induce osmotic stresses associated with the addition and removal of CPAs. To
      increase the cooling rate and reduce the CPA concentration required for
      vitrification, this study proposed an innovative approach, named forced
      convective vitrification with liquid cryogens, in which liquid oxygen at a
      temperature below its boiling point (LOX(bbp)) was used as the cryogen to reduce
      the generation of insulating bubbles of gaseous oxygen and the sample was
      subjected to a constant velocity to remove insulation bubbles from the sample.
      Results show that changing the cryogen from liquid nitrogen at its boiling
      temperature (LN(abp)) to LOX(bbp), increasing the sample velocity and reducing
      the test solution volume increased the cooling rate and thereby decreased the CPA
      concentration required for vitrification. Using the same velocity (1.2 m/s), the
      cooling rate achieved with LOX(bbp) was 2.3-fold greater than that achieved with
      LN(abp). With LOX(bbp), the increase in the sample velocity from 0.2 to 1.2 m/s
      enhanced the cooling rate by 1.9 times. With LOX(bbp), a velocity of 1.2m/s and a
      test solution volume of 1.73 MUl, the CPA concentration required for
      vitrification decreased to 25%. These results indicate that the new approach
      described here can reduce the CPA concentration required for vitrification, and
      thus decreases the toxicity and osmotic stresses associated with adding and
      removing the CPA.

PMID- 23545292
TI  - Stacked planar micro coils for single-sided NMR applications.
AB  - This paper describes planar micro structured coils fabricated in a novel
      multilayer assembly for single-sided NMR experiments. By arranging the coil's
      turns in both lateral and vertical directions, all relevant coil parameters can
      be tailored to a specific application. To this end, we implemented an
      optimization algorithm based on simulations applying finite element methods
      (FEMs), which maximizes the coil's sensitivity and thus signal-to-noise ratio
      (SNR) while incorporating boundary conditions such as the coil's electrical
      properties and a localized sensitivity needed for single-sided applications.
      Utilizing thin-film technology and microstructuring techniques, the planar
      character is kept by a sub-millimeter overall thickness. The coils are adapted to
      the Profile NMR-MOUSE(r) magnet with a homogeneous slice of about 200 MUm in
      height and a uniform depth gradient of about 20T/m. The final design of a coil
      with 20 turns, separated in four layers with five turns each, and an outer
      dimension of 4*4 mm(2) is able to measure a sample volume almost five times
      smaller than that of a state-of-the-art 14*16 mm(2) Profile NMR-MOUSE(r) coil
      with the same SNR. This allows for volume-limited measurements with high SNR and
      enables different future developments. The minimal dead time of 4 MUs facilitates
      further improvements of the SNR by echo adding techniques and the
      characterization of samples with short T2 relaxation times. Measurements on solid
      polymers like polyethylene (PE) and polypropylene (PP) with T2 components as
      short as 200 MUs approve the overall beneficial coil properties. Furthermore the
      ability to perform depth profiling with microscopic resolution is demonstrated.

PMID- 23545293
TI  - Nicotiana tabacum actin-depolymerizing factor 2 is involved in actin-driven,
      auxin-dependent patterning.
AB  - Polar transport of auxin has been identified as a central element of pattern
      formation. To address the underlying cellular mechanisms, we use the tobacco cell
      line (Nicotiana tabacum L. cv. Bright Yellow 2; BY-2) as model. We showed
      previously that cell divisions within a cell file are synchronized by polar auxin
      flow, linked to the organization of actin filaments (AF) which, in turn, is
      modified via actin-binding proteins (ABPs). From a preparatory study for
      disturbed division synchrony in cell lines overexpressing different ABPs, we
      identified the actin depolymerizing factor 2 (ADF2). A cell line overexpressing
      GFP-NtADF2 was specifically affected in division synchrony. The cell division
      pattern could be rescued by addition of Phosphatidylinositol 4,5-bisphosphate
      (PIP2) or by phalloidin. These observations allow to draw first conclusions on
      the pathway linking auxin signalling via actin reorganization to synchronized
      cell division placing the regulation of cortical actin turnover by ADF2 into the
      focus.

PMID- 23545294
TI  - Evidence for exposure-induced DNA repair abnormality is indicative of health and
      genetic risk.
AB  - A recent focus has been targeted toward the development of functional biomarkers
      that can be used to predict disease more reliably. One such biomarker is the
      challenge assay for DNA repair deficiency. Briefly, the assay involves
      challenging lymphocytes in culture to a DNA damaging agent in vitro and
      determining the repair outcome in chromosome aberrations and/or DNA strand
      breaks. The aim is to show that individuals who have chronic exposure to toxic
      substances will develop exposure-induced DNA repair deficiencies. Many studies
      around the world have shown that the assay detects DNA repair deficiency in
      environmentally/occupationally exposed populations and with significant exposure
      dose-response relationship. The prediction of health risk was also validated. In
      addition, exposure-induced repair deficiency which was apparently passed through
      the germ cells had caused genetic consequences in a 3-generation population. The
      assay is simple to conduct and is more sensitive than some traditional biomarker
      assays. Together with the functional significance of the assay, the challenge
      assay can be used with confidence in population studies for health risk
      assessment. 

PMID- 23545295
TI  - Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection
      and intestinal inflammation only in the context of the dense granule protein
      GRA15.
AB  - Toxoplasma gondii transmission between intermediate hosts is dependent on the
      ingestion of walled cysts formed during the chronic phase of infection.
      Immediately following consumption, the parasite must ensure survival of the host
      by preventing adverse inflammatory responses and/or by limiting its own
      replication. Since the Toxoplasma secreted effectors rhoptry 16 kinase (ROP16)
      and dense granule 15 (GRA15) activate the JAK-STAT3/6 and NF-kappaB signaling
      pathways, respectively, we explored whether a particular combination of these
      effectors impacted intestinal inflammation and parasite survival in vivo. Here we
      report that expression of the STAT-activating version of ROP16 in the type II
      strain (strain II+ROP16I) promotes host resistance to oral infection only in the
      context of endogenous GRA15 expression. Protection was characterized by a lower
      intestinal parasite burden and dampened inflammation. Host resistance to the
      II+ROP16I strain occurred independently of STAT6 and the T cell coinhibitory
      receptors B7-DC and B7-H1, two receptors that are upregulated by ROP16. In
      addition, coexpression of ROP16 and GRA15 enhanced parasite susceptibility within
      tumor necrosis factor alpha/gamma interferon-stimulated macrophages in a STAT3/6
      independent manner. Transcriptional profiling of infected STAT3- and STAT6
      deficient macrophages and parasitized Peyer's patches from mice orally challenged
      with strain II+ROP16I suggested that ROP16 activated STAT5 to modulate host gene
      expression. Consistent with this supposition, the ROP16 kinase induced the
      sustained phosphorylation and nuclear localization of STAT5 in Toxoplasma
      infected cells. In summary, only the combined expression of both GRA15 and ROP16
      promoted host resistance to acute oral infection, and Toxoplasma may possibly
      target the STAT5 signaling pathway to generate protective immunity in the gut.

PMID- 23545296
TI  - Formalin-inactivated Coxiella burnetii phase I vaccine-induced protection depends
      on B cells to produce protective IgM and IgG.
AB  - To further understand the mechanisms of formalin-inactivated Coxiella burnetii
      phase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell,
      CD4(+) T cell, or CD8(+) T cell deficiency in mice significantly affects the
      ability of PIV to confer protection against a C. burnetii infection.
      Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels
      of protection in CD4(+) T cell- or CD8(+) T cell-deficient mice and partial
      protection in T cell-deficient mice but did not provide measurable protection in
      B cell-deficient mice. These results suggest that PIV-induced protection depends
      on B cells. In addition, anti-PI-specific IgM was the major detectable antibody
      (Ab) in immune sera from PIV-vaccinated CD4(+) T cell-deficient mice, and passive
      transfer of immune sera from PIV-vaccinated CD4(+) T cell-deficient mice
      conferred significant protection. These results suggest that T cell-independent
      anti-PI-specific IgM may contribute to PIV-induced protection. Our results also
      suggested that PIV-induced protection may not depend on complement activation and
      Fc receptor-mediated effector functions. Furthermore, our results demonstrated
      that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibit C.
      burnetii infection in vivo, but only IgM from PIV-vaccinated CD4(+) T cell
      deficient mouse sera inhibited C. burnetii infection. Collectively, these
      findings suggest that PIV-induced protection depends on B cells to produce
      protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play
      a critical role in PIV-induced protection against C. burnetii infection.

PMID- 23545298
TI  - Localization of phosphatidylinositol 4,5-bisphosphate to lipid rafts and uroids
      in the human protozoan parasite Entamoeba histolytica.
AB  - Entamoeba histolytica is an intestinal protozoan parasite and is the causative
      agent of amoebiasis. During invasive infection, highly motile amoebae destroy the
      colonic epithelium, enter the blood circulation, and disseminate to other organs
      such as liver, causing liver abscess. Motility is a key factor in E. histolytica
      pathogenesis, and this process relies on a dynamic actomyosin cytoskeleton. In
      other systems, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is known to
      regulate a wide variety of cellular functions, including signal transduction,
      actin remodeling, and cell motility. Little is known about the role of PI(4,5)P2
      in E. histolytica pathogenicity. In this study, we demonstrate that PI(4,5)P2 is
      localized to cholesterol-rich microdomains, lipid rafts, and the actin-rich
      fractions of the E. histolytica membrane. Microscopy revealed that the trailing
      edge of polarized trophozoites, uroids, are highly enriched in lipid rafts and
      their constituent lipid, PI(4,5)P2. Polarization and enrichment of uroids and
      rafts with PI(4,5)P2 were enhanced upon treatment of E. histolytica cells with
      cholesterol. Exposure to cholesterol also increased intracellular calcium, which
      is a downstream effector of PI(4,5)P2, with a concomitant increase in motility.
      Together, our data suggest that in E. histolytica, PI(4,5)P2 may signal from
      lipid rafts and cholesterol may play a role in triggering PI(4,5)P2-mediated
      signaling to enhance the motility of this pathogen.

PMID- 23545297
TI  - Identification of a peptide-based neutralizer that potently inhibits both Shiga
      toxins 1 and 2 by targeting specific receptor-binding regions.
AB  - Shiga toxin (Stx) is a major virulence factor of enterohemorrhagic Escherichia
      coli that occasionally causes fatal systemic complications. We recently developed
      a tetravalent peptide (PPP-tet) that neutralizes the cytotoxicity of Stx2 using a
      multivalent peptide library approach. In this study, we used this technique to
      identify a series of tetravalent peptides that bound to Stx1, another major Stx
      family member, with high affinity by targeting one receptor-binding site of the B
      subunit. One peptide, MMA-tet, markedly inhibited Stx1 and Stx2 cytotoxicity with
      greater potency than PPP-tet. After forming a complex with Stx1 through its
      specific receptor-binding region, MMA-tet did not affect vesicular transport of
      the toxin to the endoplasmic reticulum but substantially rescued inhibition of
      the protein synthesis induced by Stx1. Oral application of MMA-tet protected mice
      from a fatal dose of an E. coli O157:H7 strain producing both toxins. MMA-tet may
      be a promising therapeutic agent against the infection.

PMID- 23545299
TI  - Hookworm excretory/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T
      cell responses and suppress pathology in a mouse model of colitis.
AB  - Evidence from human studies and mouse models shows that infection with parasitic
      helminths has a suppressive effect on the pathogenesis of some inflammatory
      diseases. Recently, we and others have shown that some of the suppressive effects
      of hookworms reside in their excretory/secretory (ES) products. Here, we
      demonstrate that ES products of the hookworm Ancylostoma caninum (AcES) suppress
      intestinal pathology in a model of chemically induced colitis. This suppression
      was associated with potent induction of a type 2 cytokine response characterized
      by coexpression of interleukin-4 (IL-4) and IL-10 by CD4(+) T cells,
      downregulation of proinflammatory cytokine expression in the draining lymph nodes
      and the colon, and recruitment of alternatively activated (M2) macrophages and
      eosinophils to the site of ES administration. Protease digestion and heat
      denaturation of AcES resulted in impaired induction of CD4(+) IL-4(+) IL-10(+)
      cell responses and diminished ability to suppress colitis, indicating that
      protein component(s) are responsible for some of the immunosuppressive effects of
      AcES. Identification of the specific parasite-derived molecules responsible for
      reducing pathology during chemically induced colitis could lead to the
      development of novel therapeutics for the treatment of human inflammatory bowel
      disease.

PMID- 23545300
TI  - Intranasal prophylaxis with CpG oligodeoxynucleotide can protect against Yersinia
      pestis infection.
AB  - Immunomodulatory agents potentially represent a new class of broad-spectrum
      antimicrobials. Here, we demonstrate that prophylaxis with immunomodulatory
      cytosine-phosphate-guanidine (CpG) oligodeoxynucleotide (ODN), a toll-like
      receptor 9 (TLR9) agonist, confers protection against Yersinia pestis, the
      etiologic agent of plague. The data establish that intranasal administration of
      CpG ODN 1 day prior to lethal pulmonary exposure to Y. pestis strain KIM D27
      significantly improves survival of C57BL/6 mice and reduces bacterial growth in
      hepatic tissue, despite paradoxically increasing bacterial growth in the lung.
      All of these CpG ODN-mediated impacts, including the increased pulmonary burden,
      are TLR9 dependent, as they are not observed in TLR9-deficient mice. The capacity
      of prophylactic intranasal CpG ODN to enhance survival does not require adaptive
      immunity, as it is evident in mice lacking B and/or T cells; however, the
      presence of T cells improves long-term survival. The prophylactic regimen also
      improves survival and reduces hepatic bacterial burden in mice challenged
      intraperitoneally with KIM D27, indicating that intranasal delivery of CpG ODN
      has systemic impacts. Indeed, intranasal prophylaxis with CpG ODN provides
      significant protection against subcutaneous challenge with Y. pestis strain CO92
      even though it fails to protect mice from intranasal challenge with that fully
      virulent strain.

PMID- 23545301
TI  - CD137 expressed on neutrophils plays dual roles in antibacterial responses
      against Gram-positive and Gram-negative bacterial infections.
AB  - Severe sepsis and septic shock caused mainly by bacterial infections are life
      threatening conditions that urge the development of novel therapies. However,
      host responses to and pathophysiology of sepsis have not been clearly understood,
      which remains a major obstacle for the development of effective therapeutics.
      Recently, we have shown that stimulation of a costimulatory molecule, CD137,
      enhanced survival of mice infected with the Gram-positive (G(+)) intracellular
      bacterium Listeria monocytogenes but decreased survival in a polymicrobial sepsis
      model. Herein, we report that CD137 deficiency or blocking of CD137 signaling
      decreased antibacterial responses of mice infected with G(+) bacteria
      (Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis) but
      increased these responses in mice infected with Gram-negative (G(-)) bacteria
      (Escherichia coli, Pseudomonas aeruginosa, and Salmonella enterica serovar
      Typhimurium). Consistent with these findings, stimulation of CD137 by
      administration of agonistic antibody enhanced responses against G(+) bacteria,
      whereas it decreased these responses against G(-) bacteria. Neutrophils were
      responsible for CD137-mediated opposite roles in control of G(+) and G(-)
      bacterial infections. Stimulation of CD137 enhanced activities of neutrophils
      against S. aureus but decreased these activities against E. coli, while CD137
      blocking produced opposite results with the stimulation of CD137 in vivo and in
      vitro. Furthermore, we found that combined signaling of CD137 and Toll-like
      receptor 2 (TLR2) induced synergistic production of tumor necrosis factor alpha
      (TNF-alpha) and interleukin-6 (IL-6) by neutrophils, but combined signaling of
      CD137 and TLR4 did not. Our data strongly suggest that CD137 may play a dual role
      in sepsis in association with TLRs.

PMID- 23545302
TI  - Heterozygosity at the A625C polymorphic site of the MyD88 gene is associated with
      Mycobacterium bovis infection in cattle.
AB  - The study demonstrates that in cattle, animals heterozygous at the MyD88 A625C
      polymorphic marker have a 5-fold reduced risk for active pulmonary tuberculosis
      (odds ratio [OR] = 0.19; P = 6 * 10(-12)). The reduced risk, however, does not
      extend to animals with latent pulmonary tuberculosis (OR = 0.83; P = 0.40).
      Heterozygosity at the A625C single nucleotide polymorphism is associated with
      intermediate levels of tumor necrosis factor alpha, gamma interferon, and nitric
      oxide synthase (NOS). Accordingly, deficiency as well as overexpression of
      proinflammatory cytokines or NOS favor tuberculosis, while heterozygosity
      provides the animals with the optimal level of inflammation.

PMID- 23545303
TI  - Candida albicans-Staphylococcus aureus polymicrobial peritonitis modulates host
      innate immunity.
AB  - Despite advances in medical device fabrication and antimicrobial treatment
      therapies, fungal-bacterial polymicrobial peritonitis remains a serious
      complication for surgery patients, those on peritoneal dialysis, and the
      critically ill. Using a murine model of peritonitis, we have demonstrated that
      monomicrobial infection with Candida albicans or Staphylococcus aureus is
      nonlethal. However, coinfection with these same doses leads to a 40% mortality
      rate and increased microbial burden in the spleen and kidney by day 1
      postinfection. Using a multiplex enzyme-linked immunosorbent assay, we have also
      identified a unique subset of innate proinflammatory cytokines (interleukin-6,
      granulocyte colony-stimulating factor, keratinocyte chemoattractant, monocyte
      chemoattractant protein-1, and macrophage inflammatory protein-1alpha) that are
      significantly increased during polymicrobial versus monomicrobial peritonitis,
      leading to increased inflammatory infiltrate into the peritoneum and target
      organs. Treatment of coinfected mice with the cyclooxygenase (COX) inhibitor
      indomethacin reduces the infectious burden, proinflammatory cytokine production,
      and inflammatory infiltrate while simultaneously preventing any mortality.
      Further experiments demonstrated that the immunomodulatory eicosanoid
      prostaglandin E2 (PGE2) is synergistically increased during coinfection compared
      to monomicrobial infection; indomethacin treatment also decreased elevated PGE2
      levels. Furthermore, addition of exogenous PGE2 into the peritoneal cavity during
      infection overrode the protection provided by indomethacin and restored the
      increased mortality and microbial burden. Importantly, these studies highlight
      the ability of fungal-bacterial coinfection to modulate innate inflammatory
      events with devastating consequences to the host.

PMID- 23545304
TI  - Toll-like receptor 4/stem cell antigen 1 signaling promotes hematopoietic
      precursor cell commitment to granulocyte development during the granulopoietic
      response to Escherichia coli bacteremia.
AB  - In response to severe bacterial infection, bone marrow hematopoietic activity
      shifts toward promoting granulopoiesis. The underlying cell signaling mechanisms
      remain obscure. To study the role of Toll-like receptor 4 (TLR4)/stem cell
      antigen-1 (Sca-1) signaling in this process, bacteremia was induced in mice by
      intravenous injection of Escherichia coli. A subgroup of animals also received
      intravenous 5-bromo-2-deoxyuridine (BrdU). In a separate set of experiments, bone
      marrow lineage-negative (lin(-)) stem cell growth factor receptor-positive (c
      kit(+)) Sca-1(-) cells containing primarily common myeloid progenitors were
      cultured in vitro without or with E. coli lipopolysaccharide (LPS). In genotypic
      background control mice, bacteremia significantly upregulated Sca-1 expression by
      lin(-) c-kit(+) cells, as reflected by a marked increase in BrdU-negative lin(-)
      c-kit(+) Sca-1(+) cells in the bone marrow. In mice with the TLR4 gene deletion,
      this bacteremia-evoked Sca-1 response was blocked. In vitro, LPS induced a dose
      dependent increase in Sca-1 expression by cultured marrow lin(-) c-kit(+) Sca-1(
      ) cells. LPS-induced upregulation of Sca-1 expression was regulated at the
      transcriptional level. Inhibition of c-Jun N-terminal kinase/stress-activated
      protein kinase (JNK) activity with the specific inhibitor SP600125 suppressed LPS
      induced upregulation of Sca-1 expression by marrow lin(-) c-kit(+) Sca-1(-)
      cells. Engagement of Sca-1 with anti-Sca-1 antibodies enhanced the expression of
      Sfpi1 spleen focus-forming virus (SFFV) proviral integration 1 (PU.1) in marrow
      lin(-) c-kit(+) Sca-1(-) cells cultured with LPS. Sca-1 null mice failed to
      maintain the marrow pool of granulopoietic cells following bacteremia. These
      results demonstrate that TLR4/Sca-1 signaling plays an important role in the
      regulation of hematopoietic precursor cell programming and their enhancement of
      granulocyte lineage commitment in response to E. coli bacteremia.

PMID- 23545306
TI  - A Populus euphratica NAC protein regulating Na+/K+ homeostasis improves salt
      tolerance in Arabidopsis thaliana.
AB  - NAC transcription factors are plant-specific and play an important role in
      responses to biotic and abiotic stresses. Populus euphratica is a salt-tolerant
      tree species growing in semi-arid saline areas. A stress responsive gene was
      successfully isolated from this species and named PeNAC1. The isolated cDNA
      encoded a protein containing a conserved NAC domain that belonged to the ATAF
      subgroup of the NAC protein family. The protein was localized to the nucleus and
      its C-terminus had transcriptional activation activity. Northern hybridization
      showed that its expression was strongly induced by drought and salt stress, but
      only slightly induced by ABA treatment in P. euphratica. Transgenic Arabidopsis
      overexpressing PeNAC1 showed enhanced tolerance to salt stress, with lower
      Na(+)/K(+) ratios in the roots and leaves, and significantly inhibited expression
      levels of AtHKT1. Our results suggest that PeNAC1 plays a role in the plant
      response to salt stress by regulating Na(+)/K(+) homeostasis.

PMID- 23545307
TI  - Cellular overexpression of aquaporins slows down the natural HIF-2alpha
      degradation during prolonged hypoxia.
AB  - Overexpression of cell membrane aquaporins (AQPs) has recently been associated
      with tumor formation, particularly with angiogenesis, cell migration and
      proliferation. Additionally, the hypoxia inducible factor (HIF) family has been
      extensively implicated in tumor growth and recent studies evidence interplay
      between AQP expression and HIF stability. Therefore, we decided to explore the
      effect that AQP overexpression has on the long-term stability of HIF-2alpha in
      PC12 cells exposed to chronic hypoxia, characteristic of a growing tumor. HIF
      2alpha levels were analyzed in five PC12 clones with stable overexpression of
      different proteins (AQP1, AQP3, AQP5, G6PD, and GDNF), in PC12 transiently
      expressing G6PD or Kv4.2, and in wild-type PC12 cells. Overexpression of AQP1, 3
      or 5 in PC12 cells (o-AQP-c) prevented the HIF-2alpha down-expression otherwise
      observed, after 16 h at 1% O2, in wt-PC12 and in PC12 overexpressing non-AQP
      proteins. Longer HIF-2alpha stability was also observed in o-AQP-c exposed to
      cobalt chloride or dimethyloxallyl glycine. Normal proteasome activity was
      confirmed in all clones analyzed. Levels of HIF target genes (PHD2 and 3, VEGF,
      and PGK1) were 2-4 fold higher in hypoxic o-AQP-c than in wt-PC12 cells, and
      morphological changes in colony shape together with higher cell proliferation
      rates were observed in all o-AQP-c. Interestingly, analysis of PHD levels under
      normoxia revealed lower (50%) PHD3 expression in o-AQP-c than in controls. Our
      results indicate that AQP overexpression in PC12 cells prolongs HIF-2alpha
      stability during chronic hypoxia, leading to higher level of induction of its
      target genes and likely conferring to these cells a more tumor-like phenotype.

PMID- 23545305
TI  - Toll-like receptor 5-dependent immunogenicity and protective efficacy of a
      recombinant fusion protein vaccine containing the nontoxic domains of Clostridium
      difficile toxins A and B and Salmonella enterica serovar typhimurium flagellin in
      a mouse model of Clostridium difficile disease.
AB  - Clostridium difficile is a spore-forming bacillus that produces toxin-mediated
      enteric disease. C. difficile expresses two major virulence factors, toxin A
      (TcdA) and toxin B (TcdB). Human and animal studies demonstrate a clear
      association between humoral immunity to these toxins and protection against C.
      difficile infection (CDI). The receptor binding-domains (RBDs) of TcdA and TcdB
      are known to be immunogenic. Here, we tested the immunoadjuvant properties of
      Salmonella enterica serovar Typhimurium flagellin (FliC) subunit D1 as an innate
      immune agonist expressed as a recombinant fusion vaccine targeting the RBDs of
      TcdA and TcdB in mice. Intraperitoneally immunized mice developed prominent anti
      TcdA and anti-TcdB immunoglobulin G in serum. The protective efficacy of the
      recombinant vaccines, with or without an adjuvant, was tested in a mouse model of
      CDI that closely represents the human disease. Following intraperitoneal
      immunization equivalent to two doses of toxoid A and toxoid B vaccine adjuvanted
      with alum and oral challenge with C. difficile VPI 10463, C57BL/6 mice were able
      to mount a protective immune response that prevented diarrhea and death compared
      to mice immunzed with alum alone. These results are significantly different from
      those for control mice (P < 0.001). These results provide evidence that a
      recombinant protein-based vaccine targeting the RBDs of the C. difficile toxins
      adjuvanted with S. Typhimurium flagellin can induce rapid, high-level protection
      in a mouse model of CDI when challenged with the homologous strain from which the
      vaccine antigens were derived and warrant further preclinical testing against
      clinically relevant C. difficile strains in the mouse and hamster models of CDI.

PMID- 23545308
TI  - Association between miR-146a rs2910164 polymorphism and autoimmune diseases
      susceptibility: a meta-analysis.
AB  - Published data on the rs2910164 in microRNA-146a (miR-146a) are shown to be
      associated with increased or decreased autoimmune diseases risk. To derive a more
      precise estimation of the relationship, we performed a meta-analysis to
      systematically summarize the possible. A meta-analysis including 11 studies with
      3042 controls and 2197 cases was performed for genotypes CC (recessive effect),
      CC+CG (dominant effect) and C allele in fixed or random-effects models based on
      between-study heterogeneity. Overall, no significant association between miR-146a
      G/C rs2910164 polymorphism and autoimmune diseases risk was found in all genetic
      models when all studies were pooled into the meta-analysis. SLE (OR=0.99, 95% CI:
      0.90-1.10), RA (OR=0.98, 95% CI: 0.85-1.14) did not yield statistical
      significance as for C allele pooled studies. In the subgroup analysis by
      ethnicity, still no significant association was detected in all genetic models.
      Our meta-analysis suggests that there is no association between miR-146a G/C
      rs2910164 polymorphism and the development of autoimmune diseases.

PMID- 23545309
TI  - Molecular cloning of a plasma membrane Ca2+ ATPase (PMCA) from Y-organs of the
      blue crab (Callinectes sapidus), and determination of spatial and temporal
      patterns of PMCA gene expression.
AB  - Existing data indicate that a stage-specific increase in intracellular free
      Ca(2+) stimulates ecdysteroid production by crustacean molting glands (Y-organs).
      The concentration of Ca(2+) in cytosol is controlled mainly by proteins intrinsic
      to the plasma membrane and to the membranes of organelles. Several families of
      proteins are involved, including Ca(2+) channels, Ca(2+) pumps (ATPases), and
      Ca(2+) exchangers. The family of Ca(2+) pumps includes plasma membrane calcium
      ATPases (PMCAs). As a step toward understanding the involvement of calcium
      signaling in regulation of ecdysteroidogenesis, we used a PCR-based cloning
      strategy (RT-PCR followed by 3'- and 5'-RACE) to clone from Y-organs of the blue
      crab (Callinectes sapidus) a cDNA encoding a putative PMCA. The 4292 base pair
      (bp) cDNA includes a 3510 bp open reading frame encoding a 1170-residue protein
      (Cas-PMCA). The conceptually translated protein has a relative molecular mass of
      128.8*10(3) and contains all signature domains of an authentic PMCA, including
      ten transmembrane domains and a calmodulin binding site. The predicted membrane
      topography of Cas-PMCA is as expected for an authentic PMCA protein. A
      phylogenetic analysis of nonredundant amino acid sequences of PMCA proteins from
      different species showed Cas-PMCA clusters with other arthropod PMCA proteins. An
      assessment of tissue distribution showed the Cas-PMCA transcript to be broadly
      distributed in both neural and non-neural tissues. Studies using quantitative
      real-time PCR revealed stage-specific changes in Cas-PMCA abundance during the
      molting cycle, with peak expression occurring during premolt stage D2, a pattern
      consistent with the hypothesis that Cas-PMCA functions to maintain cellular
      Ca(2+) homeostasis in Y-organs.

PMID- 23545310
TI  - Association between -251A>T polymorphism in the interleukin-8 gene and oral
      cancer risk: a meta-analysis.
AB  - BACKGROUND: Emerging evidence showed that the most common functional polymorphism
      (-251A>T, rs4073) in the promoter region of the interleukin-8 (IL-8) gene is
      involved in the regulation of the activities of interleukin-8, thus increasing an
      individual's susceptibility to oral cancer; but individually published results
      are inconclusive. The aim of this meta-analysis was to investigate the
      associations between IL-8 -251A>T polymorphism and oral cancer risk. METHODS: The
      PubMed, Embase, Web of Science and CBM databases were searched for all articles
      published up to October 1st, 2012 that addressed IL-8 -251A>T polymorphism and
      oral cancer risk. Statistical analyses were performed using STATA 12.0 software.
      Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess
      the strength of associations. RESULTS: Six case-control studies were included
      with a total of 1324 oral cancer cases and 1879 healthy controls. When all
      available studies were pooled into the meta-analysis, the results showed that the
      AA and AT genotypes of IL-8 -251A>T polymorphism were associated with increased
      risk of oral cancer (OR=1.23, 95% CI: 1.03-1.46, P=0.025; OR=1.25, 95% CI: 1.07
      1.47, P=0.006; respectively). In the subgroup analysis by ethnicity, significant
      associations were observed between the AA and AT genotypes of IL-8 -251A>T
      polymorphism and increased risk of oral cancer among Caucasian populations
      (OR=1.40, 95% CI: 1.14-1.72, P=0.001; OR=1.29, 95% CI: 1.06-1.57, P=0.011;
      respectively). However, no statistically significant associations were found
      between IL-8 -251A>T polymorphism and oral cancer risk among Asian populations.
      CONCLUSIONS: Results from the current meta-analysis indicate that the AA and AT
      genotypes of IL-8 -251A>T polymorphism might increase the risk of oral cancer,
      especially among Caucasian populations.

PMID- 23545311
TI  - Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is
      associated with pro-inflammatory, oxidative-glycation markers and sRAGE in
      diabetic retinopathy.
AB  - BACKGROUND: Receptor for advanced glycation end-product (RAGE) gene polymorphism
      2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on
      how it affects the disease development is still unclear. AIM: This study aims to
      investigate the relationship between 2245G/A RAGE gene polymorphism and selected
      pro-inflammatory, oxidative-glycation markers in DR patients. METHODS: A total of
      371 unrelated type 2 diabetic patients [200 with retinopathy, 171 without
      retinopathy (DNR)] and 235 healthy subjects were recruited. Genotyping was
      performed by polymerase chain reaction-restriction fragment length polymorphism
      method followed by DNA sequencing. The nuclear and cytosolic extracts from
      peripheral blood mononuclear cells were used for nuclear factor kappa B (NF
      kappaB) p65 and superoxide dismutase activity measurement respectively. Plasma
      was used for glutathione peroxidase activity, advanced oxidation protein product
      (AOPP), monocyte chemoattractant protein (MCP)-1, pentosidine and soluble RAGE
      (sRAGE) measurements. RESULTS: DR patients with 2245GA genotype had significantly
      elevated levels of activated NF-kappaB p65, plasma MCP-1, AOPP and pentosidine
      but lower level of sRAGE when compared to DR patients with wild-type 2245GG.
      CONCLUSION: The RAGE gene polymorphism 2245G/A is associated with pro
      inflammatory, oxidative-glycation markers and circulating sRAGE in DR patients.
      Patients with 2245GA RAGE genotype could aggravate DR possibly via NF-kappaB
      mediated inflammatory pathway.

PMID- 23545312
TI  - Identification of one novel mutation in the C-propeptide of COL2A1 in a Chinese
      family with spondyloperipheral dysplasia.
AB  - Spondyloperipheral dysplasia (SPD; OMIM 271700) is an autosomal dominant
      connective tissue disorder characterized by vertebral body abnormalities
      (platyspondyly, end-plate indentations), hip dysplasia and brachydactyly type E.
      Here, we identified a novel truncating mutation (p.Lys1444AsnfsX27) in the C
      propeptide of type II collagen in an affected Chinese individual with SPD. Our
      findings will provide clues to the phenotype-genotype relations and may assist
      not only in the clinical diagnosis of SPD but also in the interpretation of
      genetic information used for prenatal diagnosis and genetic counseling.

PMID- 23545313
TI  - Prenatal diagnosis and molecular cytogenetic characterization of a de novo
      interstitial deletion of 7q (7q22.1->q31.1).
AB  - We present prenatal diagnosis and molecular cytogenetic characterization of de
      novo interstitial deletion of 7q (7q22.1->q31.1) by aCGH, FISH and QF-PCR in a
      fetus with an abnormal maternal serum screening result and ultrasound findings of
      facial cleft and hypogenitalism. We discuss the genotype-phenotype correlation
      and the consequence of haploinsufficiency of ZKSCAN5, ARPC1A, CYP3A43, RELN,
      LAMB1, IMMP2L and DOCK4 in this case.

PMID- 23545314
TI  - Familial porphyria cutanea tarda in Spain: characterization of eight novel
      mutations in the UROD gene and haplotype analysis of the common p.G281E mutation.
AB  - Porphyria cutanea tarda (PCT) results from decreased activity of uroporphyrinogen
      decarboxylase (UROD) in the liver. Deficiency in this enzyme results in
      accumulation of highly carboxylated porphyrins responsible for the disease. PCT
      usually occurs in adulthood and is characterized by cutaneous photosensitivity,
      hyperpigmentation, skin fragility and hypertrichosis. Familial PCT (F-PCT) occurs
      in 20-30% of patients in whom UROD gene mutations in heterozygosity decrease the
      enzymatic activity to about 50% in all tissues. The rare homozygous form of F-PCT
      (hepatoerythropoietic porphyria) has more severe clinical features and onset in
      childhood. In Spain, F-PCT is molecularly heterogeneous and the most frequent
      UROD mutation is p.G281E. In the present study, we searched for the molecular
      defect causing F-PCT in a group of Spanish patients and investigated whether the
      p.G281E mutation in the Spanish population came from a single or various origins.
      Among seventeen F-PCT patients, sixteen UROD mutations were identified, including
      eight novel ones: six missense (p.A23V, p.L78P, p.W180G, p.T196I, p.E278G and
      p.V279M), one frameshift (c.233delT) and one splice site mutation (c.774G>C).
      Prokaryotic expression studies showed the detrimental effect for each missense
      mutation, whereas reverse transcription-PCR and sequencing demonstrated that the
      novel splice site mutation caused exon 7 skipping. Moreover, haplotype analysis
      performed in Spanish families with the p.G281E mutation indicated that this
      lesion is associated with at least five haplotype backgrounds. These results
      extend knowledge on the molecular heterogeneity of F-PCT and suggest multiple
      origins of the p.G281E mutation.

PMID- 23545315
TI  - Further evidence for the contribution of the vascular endothelial growth factor
      gene in coronary artery disease susceptibility.
AB  - Coronary artery disease (CAD) receives intensive attentions in the research of
      cardiovascular diseases, due to its high incidence and severe impact on the
      quality of life vascular endothelial growth factor (VEGF), a potent angiogenic
      and vascular permeability factor, has been strongly implicated in the
      pathogenesis of CAD. Genetic markers in different regions of the VEGF gene have a
      plausible role in modulating the risk of CAD. To identify the markers
      contributing to the genetic susceptibility to CAD, we examined the potential
      association between CAD and 10 single nucleotide polymorphisms (SNPs, rs699947,
      rs1570360, rs2010963, rs833068, rs3024997, rs3025000, rs3025010, rs3025020,
      rs3025030, rs3025039) of the VEGF gene using the MassARRAY system. Participants
      included 242 CAD patients and 253 healthy controls from a Chinese Han Population
      (He'nan Province, China). The allelic or genotypic frequencies of the rs699947
      (5' untranslated regions, 5'UTR) and rs2010963 (5'UTR) polymorphisms in the CAD
      patients were significantly different from those in the healthy controls. The CAD
      patients had significantly higher frequency of the rs699947 A allele
      (chi(2)=11.141, P=0.001, OR=1.665, 95% CI=1.232-2.250) and rs2010963 C allele
      (chi(2)=13.593, P=0.0002, OR=1.611, 95% CI=1.249-2.077). Strong linkage
      disequilibrium was observed in the rs699947-rs1570360-rs2010963 haplotype block
      (D'>0.9). Significantly more C-G-C haplotypes (P=0.040) and significantly fewer C
      G-G haplotypes (P=0.0004) were found in the CAD patients. The possible
      association of rs699947 and rs2010963 with CAD risks warrant confirmation in
      independent case-control studies and may be informative for future investigations
      on the pathogenesis of CAD.

PMID- 23545316
TI  - Ring chromosome 21 presenting with sacrococcygeal teratoma: prenatal diagnosis,
      molecular cytogenetic characterization and literature review.
AB  - We present perinatal findings and molecular cytogenetic characterization of a
      prenatally detected sacrococcygeal teratoma associated with mosaic r(21). This is
      the first report of mosaic r(21) presenting with a fetal sacrococcygeal teratoma.
      We discuss cytogenetic abnormalities associated with fetal sacrococcygeal
      teratomas.

PMID- 23545317
TI  - Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: a meta
      analysis.
AB  - Studies investigating the association between interleukin-13 (IL-13) single
      nucleotide polymorphism (SNP) rs20541 and allergic rhinitis (AR) risk have
      reported conflicting results. The aim of the present study was to conduct a meta
      analysis assessing the possible association of IL-13 SNP rs20541 with AR risk.
      Eight studies were included in the present meta-analysis (2153 cases and 3931
      controls). The combined results based on all studies showed that IL-13 SNP
      rs20541 was associated with increased AR risk (Gln versus Arg: odds ratio
      (OR)=1.18, 95% confidence interval (CI)=1.08-1.30; Gln/Gln versus Arg/Arg:
      OR=1.52, 95% CI=1.20-1.92; Arg/Gln+Gln/Gln versus Arg/Arg: OR=1.19, 95% CI=1.06
      1.33; Gln/Gln versus Arg/Gln+Arg/Arg: OR=1.42, 95% CI=1.13-1.79). When
      stratifying for race, IL-13 SNP rs20541 exhibited increased AR risk in Asians
      (Gln versus Arg: OR=1.20, 95% CI=1.06-1.36; Gln/Gln versus Arg/Arg: OR=1.57, 95%
      CI=1.17-2.12; Arg/Gln+Gln/Gln versus Arg/Arg: OR=1.22, 95% CI=1.04-1.44; Gln/Gln
      versus Arg/Gln+Arg/Arg: OR=1.45, 95% CI=1.09-1.93), while no significant
      association was detected in Caucasians (Gln versus Arg: OR=1.28, 95%
      CI=0.93~1.78; Gln/Gln versus Arg/Arg: OR=1.42, 95% CI=0.96-2.11; Arg/Gln+Gln/Gln
      versus Arg/Arg: OR=1.35, 95% CI=0.89-2.05; Gln/Gln versus Arg/Gln+Arg/Arg:
      OR=1.37, 95% CI=0.93-2.02). This meta-analysis supported that IL-13 SNP rs20541
      was associated with AR, particularly in Asians.

PMID- 23545318
TI  - Validation of minor stroke definitions for thrombolysis decision making.
AB  - BACKGROUND: Patients with low National Institutes of Health Stroke Scale (NIHSS)
      scores are frequently excluded from thrombolysis, but more than 25% of them
      remain disabled. We sought to define a validated minor stroke definition to
      reduce the inappropriate treatment exclusion. METHODS: From an outcome database,
      untreated patients with an NIHSS score of 5 or less presenting within a 4.5-hour
      window were identified and 3-month modified Rankin Scale (mRS) outcomes were
      analyzed according to individual isolated symptoms and total NIHSS scores. The
      validity of the following minor stroke definitions were assessed: (1) the
      National Institute of Neurological Disorders and Stroke Tissue Plasminogen
      Activator (NINDS-TPA) trials' definition, (2) the total NIHSS score, varying a
      cutoff point from 0 to 4, and (3) our proposed definition that included an NIHSS
      score = 0 or an NIHSS score = 1 on the items of level of consciousness (LOC),
      gaze, facial palsy, sensory, or dysarthria. RESULTS: Of 647 patients, 172
      patients (26.6%) had a 3-month unfavorable outcome (mRS score 2-6). Favorable
      outcome was achieved in more than 80% of patients with an NIHSS score of 1 or
      less or with an isolated symptom on the LOC, gaze, facial palsy, sensory, or
      dysarthria item. In contrast, unfavorable outcome proportion was more than 25% in
      patients with an NIHSS score of 2 or more. When the NINDS-TPA trials' definition,
      our definition, or the definition of an NIHSS score of 1 or less were applied,
      more than 75% of patients with an unfavorable outcome were defined as a non-minor
      stroke and less than 15% of patients with an unfavorable outcome were defined as
      a minor stroke. CONCLUSION: Implementation of an optimal definition of minor
      stroke into thrombolysis decision-making process would decrease the unfavorable
      outcomes in patients with low NIHSS scores.

PMID- 23545319
TI  - Recent trends in inpatient mortality and resource utilization for patients with
      stroke in the United States: 2005-2009.
AB  - BACKGROUND: The aim of the study is to evaluate recent trends in mortality,
      length of stay, costs, and charges for patients admitted to the US hospitals with
      the principal diagnosis of stroke. METHODS: This was a retrospective temporal
      trends study using data from the Nationwide Inpatient Sample from 2005 to 2009.
      RESULTS: During the study period, there were 2.7 million hospital admissions with
      the diagnosis of stroke in the United States (470,000 intracerebral hemorrhage,
      130,000 subarachnoid hemorrhage, and 2.1 million ischemic strokes). In-hospital
      mortality decreased from 10.2% in 2005 to 9.0% in 2009 (26.0%-23.0%, 23.4%-23.1%,
      and 6.0%-5.1% for the stroke subtypes, respectively), the average length of stay
      decreased from 6.3 days to 5.9 days (5.6-5.2 days for ischemic stroke, remained
      the same for hemorrhagic stroke), and the average number of 1.3 +/- 0.1
      procedures per admission remained the same. The proportion of patients with major
      or extreme severity of illness increased from 39.2% to 47.0% (P < .0001). After
      adjustment for inflation, the average total charge per admission increased from
      $36,215 to $46,518 (P < .0001), whereas the average cost of treatment remained
      the same. Higher treatment cost is associated with lower in-hospital mortality
      after adjustment for demographic, hospital-related, and clinical confounders
      (odds ratio = .968 [.965-.970] per each extra $1000). CONCLUSIONS: Between 2005
      and 2009, in-hospital mortality for patients hospitalized with stroke improved
      despite increasing severity of illness. At the same time, the average charge for
      hospitalization increased by 28% despite unchanged cost of treatment and shorter
      length of stay.

PMID- 23545320
TI  - Electrocardiographic assessment of coronary artery disease and stroke risk
      factors in rural and urban Tanzania: a case-control study.
AB  - BACKGROUND: Although the association between cerebrovascular and coronary artery
      disease (CAD) is well known in high-income countries, this association is not
      well documented in black Africans. AIMS: The aim of this study was to document
      electrocardiographic (ECG) evidence of CAD in stroke cases and controls and to
      identify other common ECG abnormalities related to known stroke risk factors in a
      community-based population of incident stroke cases in Tanzania, East Africa.
      METHODS: This was a case-control study. Incident stroke cases were identified by
      the Tanzanian Stroke Incidence Project. Age- and sex-matched controls were
      randomly selected from the background population. Electrocardiograms were
      manually analyzed using the Minnesota Coding System, looking for evidence of
      previous myocardial infarction (MI), atrial fibrillation (AF) or atrial flutter
      (AFl), and left ventricular hypertrophy (LVH). RESULTS: In Hai, there were 93
      cases and 241 controls with codable electrocardiograms, and in Dar-es-Salaam,
      there were 39 cases and 72 controls with codable electrocardiograms. Comparing
      cases and controls, there was a higher prevalence of MI and AF or AFl (but not
      LVH) in cases compared with controls. CONCLUSIONS: This is the first published
      study of ECG assessment of CAD and other stroke risk factors in an incident
      population of stroke cases in sub-Saharan Africa. It suggests that concomitant
      CAD in black African stroke cases is more common than previously suggested.

PMID- 23545321
TI  - Fatal multiple systemic emboli after intravenous thrombolysis for cardioembolic
      stroke.
AB  - Our objective is to present a case of fatal multiple systemic emboli after
      intravenous thrombolysis for cardioembolic stroke. A 64-year-old woman with
      atrial fibrillation was admitted for evaluation of sudden consciousness
      disturbance, right hemiplegia, and aphasia. Diffusion-weighted imaging showed no
      early ischemic changes of the brain, and magnetic resonance angiography (MRA)
      showed occlusion of the left middle cerebral artery (MCA). One hour after
      initiation of 0.6 mg/kg of intravenous alteplase, the MCA was partially
      recanalized. Her symptoms disappeared the following day. We began intravenous
      heparin for secondary prevention of cardioembolic stroke. However, on the third
      day (52 hours after thrombolysis), she suddenly developed a coma and left
      hemiplegia. MRA showed acute occlusion of the right internal carotid artery
      (ICA). She developed acute kidney injury and sudden shock and then died of fatal
      cardiorespiratory arrest on the fourth day. Autopsy revealed occlusion of the
      mitral valve orifice by a spherical fresh red thrombus that led from the left
      atrial appendage. Acute embolic infarcts were identified in the spleen and right
      kidney, the latter secondary to occlusion of the right renal artery with fresh
      red thrombus. Intravenous thrombolysis and subsequent anticoagulation therapy may
      destabilize pre-existing intracardiac thrombus, potentially leading to recurrent
      stroke, multiple systemic embolisms, and the fatal "hole-in-one" effect. 

PMID- 23545322
TI  - The expression of the let-7 miRNAs and Lin28 signalling pathway in human term
      gestational tissues.
AB  - INTRODUCTION: Labour and delivery are processes associated with inflammation
      within intrauterine and cervical tissues. The mechanisms that induce labour
      associated changes and, in particular, the role of microRNAs (miRNAs) remain to
      be elucidated. MiRNAs are small non-coding RNAs that repress gene expression via
      mRNA degradation and translational repression. Let-7 miRNAs are negatively
      regulated by RNA-binding protein, Lin28, and both function downstream of NF
      kappaB signalling. In non-gestational tissues, let-7 and Lin28 reportedy function
      as negative and positive regulators of IL-6 expression. We hypothesised that
      labour-associated inflammation involves the downregulation of let-7 miRNAs and
      upregulation of Lin28 expression. AIM: To determine the expression of Lin28
      protein and let-7 miRNA in human gestational tissue obtained before and after
      labour. METHOD: Gestational tissues were collected from women at term by
      Caesarean section with and without labour and following normal vaginal delivery
      (n = 6 per group). Protein and RNA was extracted and Lin28 and let-7 miRNA
      expression was measured by Western blotting and real-time PCR. RESULTS: The data
      obtained established that let-7 miRNA and Lin28 display tissue-specific
      expression: Lin28 was strongly expressed in the placenta and choriodecidua, but
      not measurable in amnion; and let-7b and -7c expression were significantly lower
      in choriodecidua compare to placenta and amnion, whereas the amnion expressed
      less let-7d and -7f than other tissues. CONCLUSION: While the expression of Lin28
      protein and let-7 miRNA did not vary significantly with labour onset and
      delivery, changes in their bioactivity and impact on nuclear signalling pathways
      in human gestational tissues remain to be established.

PMID- 23545323
TI  - Evidence of vertical transmission of lumpy skin disease virus in Rhipicephalus
      decoloratus ticks.
AB  - Lumpy skin disease (LSD) is an economically important acute or sub-acute disease
      of cattle that occurs across Africa and in the Middle East. The aim of this study
      was to assess whether Rhipicephalus decoloratus ticks were able to transmit lumpy
      skin disease virus (LSDV) transovarially. Uninfected, laboratory-bred R.
      decoloratus larvae were placed to feed on experimentally infected "donor" cattle.
      After completion of the life cycle on donor animals, fully engorged adult female
      ticks were harvested and allowed to lay eggs. Larvae that hatched from these eggs
      were then transferred to feed on uninfected "recipient" cattle. The latter became
      viraemic and showed mild clinical disease with characteristic skin lesions and
      markedly enlarged precrural and subscapular lymph nodes. This is the first report
      of transovarial transmission of poxviruses by R. decoloratus ticks, and the
      importance of this mode of transmission in the spread of LSDV in endemic settings
      requires further investigation.

PMID- 23545325
TI  - Synthesis and conformational analysis of neoglycoconjugates derived from O- and S
      glucose.
AB  - Using olefin metathesis as a key step, four neoglycoconjugates incorporating
      alpha-O-glucose, alpha-S-glucose or beta-S-glucose as a carbohydrate unit and L
      serine or L-cysteine as an amino acid moiety have been synthesized. The four-atom
      carbon spacer allows the carbohydrate to explore a wide-ranging conformational
      space, which may have important implications for the molecular recognition of
      these molecules.

PMID- 23545324
TI  - Electrochemical characterization of globotriose-containing self-assembled
      monolayers on nanoporous gold and their binding of soybean agglutinin.
AB  - Self-assembled monolayers (SAMs) of alpha-D-Gal-(1->4)-beta-D-Gal-(1->4)-beta-D
      Glc-mercaptooctane (globotriose, Gb3-C8-SH) were prepared both as single
      component SAMs and as mixed SAMs with either octanethiol (OCT) or 8-mercapto-3,6
      dioxaoctanol (HO-PEG2-SH), on flat gold and on nanoporous gold (NPG) electrodes.
      The binding of soybean agglutinin (SBA) to the globotriose (Gb3) unit in the SAMs
      was then studied using electrochemical impedance spectroscopy (EIS), which is a
      label free method found to be quite sensitive to SAM composition and to the
      differences in SAM structure on NPG versus on flat Au. The affinity of SBA to the
      mixed SAM of HO-PEG2-SH and Gb3-C8-SH on NPG is found to be greater on NPG than
      on flat gold, and indicates a potential advantage for NPG as a substrate. The
      SAMs of HO-PEG2-SH were found to resist protein adsorption on either NPG or flat
      gold. The non-specific adsorption of SBA to OCT SAMs on flat Au was observed in
      EIS by the increase in charge transfer resistance; whereas, the increase seen on
      the NPG surface was smaller, and suggests that EIS measurements on NPG are less
      affected by non-specific protein adsorption. Atomic force microscopy (AFM) images
      of the SBA binding to mixed SAM of HO-PEG2-SH and Gb3-C8-SH on NPG showed a
      greater number of proteins on top of the OCT containing SAMs.

PMID- 23545326
TI  - Impact of four training conditions on physician use of a web-based clinical
      decision support system.
AB  - BACKGROUND: Training has been identified as an important barrier to
      implementation of clinical decision support systems (CDSSs), but little is known
      about the effectiveness of different training approaches. METHODS: Using an
      observational retrospective cohort design, we examined the impact of four
      training conditions on physician use of a CDSS: (1) computer lab training with
      individualized follow-up (CL-FU) (n=40), (2) computer lab training without follow
      up (CL) (n=177), (3) lecture demonstration (LD) (n=16), or (4) no training (NT)
      (n=134). Odds ratios of any use and ongoing use under training conditions were
      compared to no training over a 2-year follow-up period. RESULTS: CL-FU was
      associated with the highest percent of active users and odds for any use (90.0%,
      odds ratio (OR)=10.2, 95% confidence interval (CI): 3.2-32.9) and ongoing use
      (60.0%, OR=6.1 95% CI: 2.6-13.7), followed by CL (any use=81.4%, OR=5.3, CI: 2.9
      9.6; ongoing use=28.8%, OR=1.7, 95% CI: 1.0-3.0). LD was not superior to no
      training (any use=47%, ongoing use=22.4%). CONCLUSION: Training format may have
      differential effects on initial and long-term follow-up of CDSSs use by
      physicians.

PMID- 23545327
TI  - A pilot study of distributed knowledge management and clinical decision support
      in the cloud.
AB  - OBJECTIVE: Implement and perform pilot testing of web-based clinical decision
      support services using a novel framework for creating and managing clinical
      knowledge in a distributed fashion using the cloud. The pilot sought to (1)
      develop and test connectivity to an external clinical decision support (CDS)
      service, (2) assess the exchange of data to and knowledge from the external CDS
      service, and (3) capture lessons to guide expansion to more practice sites and
      users. MATERIALS AND METHODS: The Clinical Decision Support Consortium created a
      repository of shared CDS knowledge for managing hypertension, diabetes, and
      coronary artery disease in a community cloud hosted by Partners HealthCare. A
      limited data set for primary care patients at a separate health system was
      securely transmitted to a CDS rules engine hosted in the cloud. Preventive care
      reminders triggered by the limited data set were returned for display to
      clinician end users for review and display. During a pilot study, we (1)
      monitored connectivity and system performance, (2) studied the exchange of data
      and decision support reminders between the two health systems, and (3) captured
      lessons. RESULTS: During the six month pilot study, there were 1339 patient
      encounters in which information was successfully exchanged. Preventive care
      reminders were displayed during 57% of patient visits, most often reminding
      physicians to monitor blood pressure for hypertensive patients (29%) and order
      eye exams for patients with diabetes (28%). Lessons learned were grouped into
      five themes: performance, governance, semantic interoperability, ongoing
      adjustments, and usability. DISCUSSION: Remote, asynchronous cloud-based decision
      support performed reasonably well, although issues concerning governance,
      semantic interoperability, and usability remain key challenges for successful
      adoption and use of cloud-based CDS that will require collaboration between
      biomedical informatics and computer science disciplines. CONCLUSION: Decision
      support in the cloud is feasible and may be a reasonable path toward achieving
      better support of clinical decision-making across the widest range of health care
      providers.

PMID- 23545329
TI  - Transcriptional regulation of the peripheral nervous system in Ciona
      intestinalis.
AB  - The formation of the sensory organs and cells that make up the peripheral nervous
      system (PNS) relies on the activity of transcription factors encoded by proneural
      genes (PNGs). Although PNGs have been identified in the nervous systems of both
      vertebrates and invertebrates, the complexity of their interactions has
      complicated efforts to understand their function in the context of their
      underlying regulatory networks. To gain insight into the regulatory network of
      PNG activity in chordates, we investigated the roles played by PNG homologs in
      regulating PNS development of the invertebrate chordate Ciona intestinalis. We
      discovered that in Ciona, MyT1, Pou4, Atonal, and NeuroD-like are expressed in a
      sequential regulatory cascade in the developing epidermal sensory neurons (ESNs)
      of the PNS and act downstream of Notch signaling, which negatively regulates
      these genes and the number of ESNs along the tail midlines. Transgenic embryos
      mis-expressing any of these proneural genes in the epidermis produced ectopic
      midline ESNs. In transgenic embryos mis-expressing Pou4, and MyT1 to a lesser
      extent, numerous ESNs were produced outside of the embryonic midlines. In
      addition we found that the microRNA miR-124, which inhibits Notch signaling in
      ESNs, is activated downstream of all the proneural factors we tested, suggesting
      that these genes operate collectively in a regulatory network. Interestingly,
      these factors are encoded by the same genes that have recently been demonstrated
      to convert fibroblasts into neurons. Our findings suggest the ascidian PNS can
      serve as an in vivo model to study the underlying regulatory mechanisms that
      enable the conversion of cells into sensory neurons.

PMID- 23545330
TI  - Environmental tobacco smoke exposure and brain development: the case of attention
      deficit/hyperactivity disorder.
AB  - Environmental tobacco smoke, inhaled by active firsthand smokers and their
      entourage, is associated with morbidity and mortality. Many children are
      passively exposed to secondhand smoke worldwide. Infants and young children
      account for the largest global disease burden associated with prenatal and
      postnatal secondhand smoke, probably due to underdeveloped neurological, immune,
      and respiro-circulatory systems. There is an increasingly robust association
      between tobacco smoke exposure, before and after birth, and executive function
      problems in children, adding to current and future disease burden estimates in
      public health. This review summarizes research advancements which address the
      link between environmental tobacco smoke and the development of attention
      deficits and hyperactive behavior, both as symptoms and as part of a mental
      health disorder in childhood. The multiple effects of tobacco smoke inhalation
      are best understood in terms of disruptions in normative processes involving
      cellular communication, structural development, and epigenetic influences which
      have the potential to become intergenerational. It is concluded that public
      health efforts be directed toward increasing parental awareness and compliance
      with existing guidelines that recommend no safe level of exposure. 

PMID- 23545331
TI  - Neuropsychological and neurobehavioral functioning in Duchenne muscular
      dystrophy: a review.
AB  - Duchenne muscular dystrophy (DMD) is a genetic condition affecting predominantly
      boys that is characterized by fatal muscle weakness. While there is no cure,
      recent therapeutic advances have extended the lifespan of those with DMD
      considerably. Although the physiological basis of muscle pathology is well
      documented, less is known regarding the cognitive, behavioral, and psychosocial
      functioning of those afflicted. Several lines of evidence point to central
      nervous system involvement as an organic feature of DMD, challenging our view of
      the disorder as strictly neuromuscular. This report provides a review of the
      literature on neuropsychological and neurobehavioral functioning in DMD. Recent
      research identifying associations with DMD and neuropsychiatric disorders is also
      discussed. Lastly, the review presents implications of findings related to
      nonmotor aspects of DMD for improving the quality of life in those affected.
      While the literature is often contradictory in nature, this review highlights
      some key findings for consideration by clinicians, educators and parents when
      developing therapeutic interventions for this population.

PMID- 23545332
TI  - Anatomy of a successful practice-changing study: a Blood and Marrow
      Transplantation Clinical Trials Network-National Cancer Institute Cooperative
      Group collaboration.

PMID- 23545333
TI  - Pharmacophore modeling, homology modeling, and in silico screening reveal
      mammalian target of rapamycin inhibitory activities for sotalol, glyburide,
      metipranolol, sulfamethizole, glipizide, and pioglitazone.
AB  - Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and member of
      the PI3K-related kinase (PIKK) family. It plays a central role in integrating
      signals from metabolism, energy homeostasis, cell cycle, and stress response.
      Aberrant PI3K/mTOR activation is commonly observed in diseases such as cancer,
      diabetes and Alzheimer's disease. Accordingly, we developed common feature
      binding hypotheses for a set of 6 potent mTOR antagonists. The generated models
      were validated using receiver operating characteristic (ROC) curve analyses. To
      gain better insight into ligand-mTOR interactions, a homology model for the
      kinase domain of mTOR was built using the crystallographic structure of PI3Kgamma
      as template. The optimal pharmacophore model was further improved based on
      detailed docking studies of potent training compound in the homology model. The
      modified binding model was employed as 3D search query to screen our in-house
      built database of established drugs. Subsequent in vitro screening of captured
      hits showed that six of them have submicromolar to low micromolar bioactivities,
      namely, glyburide, metipranolol, sulfamethizole, glipizide, pioglitazone, and
      sotalol.

PMID- 23545328
TI  - Following the 'tracks': Tramtrack69 regulates epithelial tube expansion in the
      Drosophila ovary through Paxillin, Dynamin, and the homeobox protein Mirror.
AB  - Epithelial tubes are the infrastructure for organs and tissues, and tube
      morphogenesis requires precise orchestration of cell signaling, shape, migration,
      and adhesion. Follicle cells in the Drosophila ovary form a pair of epithelial
      tubes whose lumens act as molds for the eggshell respiratory filaments, or dorsal
      appendages (DAs). DA formation is a robust and accessible model for studying the
      patterning, formation, and expansion of epithelial tubes. Tramtrack69 (TTK69), a
      transcription factor that exhibits a variable embryonic DNA-binding preference,
      controls DA lumen volume and shape by promoting tube expansion; the tramtrack
      mutation twin peaks (ttk(twk)) reduces TTK69 levels late in oogenesis, inhibiting
      this expansion. Microarray analysis of wild-type and ttk(twk) ovaries, followed
      by in situ hybridization and RNAi of candidate genes, identified the
      Phospholipase B-like protein Lamina ancestor (LAMA), the scaffold protein
      Paxillin, the endocytotic regulator Shibire (Dynamin), and the homeodomain
      transcription factor Mirror, as TTK69 effectors of DA-tube expansion. These genes
      displayed enriched expression in DA-tube cells, except lama, which was expressed
      in all follicle cells. All four genes showed reduced expression in ttk(twk)
      mutants and exhibited RNAi phenotypes that were enhanced in a ttk(twk)/+
      background, indicating ttk(twk) genetic interactions. Although previous studies
      show that Mirror patterns the follicular epithelium prior to DA tubulogenesis, we
      show that Mirror has an independent, novel role in tube expansion, involving
      positive regulation of Paxillin. Thus, characterization of ttk(twk)
      differentially expressed genes expands the network of TTK69 effectors, identifies
      novel epithelial tube-expansion regulators, and significantly advances our
      understanding of this vital developmental process.

PMID- 23545334
TI  - Worksite wellness: increasing adoption of workplace health promotion programs.
AB  - Worksite wellness programs are important interventions to protect and promote
      employee health. They help reduce direct and indirect health care costs,
      absenteeism, and presenteeism; avoid illness or injury; and improve the quality
      of work life and morale. This Tool introduces key concepts and strategic tips for
      planning workplace-based wellness programs rather than individual health
      promotion events, while highlighting organizational change and development
      theories central to introducing and implementing effective proactive worksite
      wellness programs.

PMID- 23545335
TI  - Needs assessment in genomic education: a survey of health educators in the United
      States.
AB  - The knowledge of genomic discoveries has been expanding daily, holding enormous
      potential to improve population health. Nevertheless, the training of health
      educators about genomics is lagging behind. To facilitate the movement of
      genomics into health promotion practice, as the first step, we conducted the
      first national survey to examine genomic education needs among health educators
      in the United States. A total of 980 health educators holding the Certified
      Health Education Specialist designation completed our web-based survey. The
      majority of participants reported that they had limited knowledge and training in
      genomics and were interested in seeking genomic education. Their first three
      preferred educational topics included genomic disorders/diseases (68.2%), family
      health history or genetic risk assessments (55.5%), and how to link genomics to
      health promotion (51.0%). A few contents, including basic genomic concepts,
      communication skills, and how to integrate genomics into routine professional
      tasks, were important to health educators' practice in genomics, but respondents
      seemed to be less favorable toward learning these contents. Continuing education
      (89.4%), web-based training (85.9%), and professional conferences (76.7%) were
      participants' top three desired delivery methods. This study will help guide the
      development, implementation, and evaluation of future genomic training programs
      for U.S. health educators. 

PMID- 23545336
TI  - [Ocular and neuro-ophthalmic manifestations of sarcoidosis: retrospective study
      of 30 cases].
AB  - INTRODUCTION: The purpose of this study was to describe the diagnostic strategy
      and therapeutic approach when sarcoidosis of the visual pathways is suspected, by
      way of a descriptive study of sarcoidosis patients in the ophthalmology services
      in Tours, Rennes and Angers. PATIENTS AND METHODS: A multicenter, retrospective
      chart review was performed for 30 patients diagnosed with sarcoidosis and
      followed at the university hospitals of Tours, Rennes and Angers between January
      1997 and August 2011. The diagnosis of sarcoidosis was based on a combination of
      clinical and ancillary tests, including pathologic confirmation and/or
      hyperlymphocytosis with a CD4/CD8 ratio greater than 5 on bronchoalveolar lavage.
      RESULTS: We identified 30 patients with ocular and/or neuro-ophthalmic
      sarcoidosis (25 female [83%], five male [17%], median age 48 years (36-87).
      Histologic confirmation of epithelioid granuloma was obtained in 24 (80%) of the
      30 included patients. Sarcoid uveitis was present in 83% of patients;
      neurosarcoidosis was found in 37% of patients. Additional complaints at
      presentation included dyspnea (31%), arthralgia (41%), myalgia (24%) and
      paresthesia (27%). Bilateral ocular involvement was found in 89% of cases. In 83%
      of patients, there was an active anterior uveitis on slit lamp examination at
      initial presentation. Funduscopic abnormalities included vitritis in 67%,
      snowbanking in 13%, snowballs in 27% and disc edema in 30%. Eight patients (27%)
      had retinal vasculitis and nine patients (30%) were diagnosed with multifocal
      choroiditis on angiography. An elevated angiotensin-converting enzyme was present
      in 13 (52%) of 25 patients tested, with an average of 71 (range 36-241). Evidence
      of sarcoidosis was present on chest CT in 22 (79%) of 28 patients. Neuroimaging
      abnormalities on brain MRI were found in eight of ten tested patients. The 10 IU
      tuberculin skin test was negative in all tested patients (12). Median
      lymphocytosis in the bronchoalveolar lavage fluid (BALF) was 0.3 (0.2-0.7) in the
      15 tested patients. BALF CD4/CD8 ratio was positive in all tested patients (12).
      Oral corticosteroids were initiated at 1mg/kg per day and then tapered in 20
      (67%) of 30 patients. Median duration of steroid treatment was 12 months (5-127),
      resulting in rapid improvement in 84% of cases. However, nearly half of patients
      experienced a recurrence of the disease. CONCLUSION: Positive diagnosis of
      sarcoidosis requires a careful history and clinical examination, ancillary
      testing, and collaboration among several medical specialties. Normal angiotensin
      converting enzyme levels do not rule out the diagnosis, since in our series, they
      were normal in almost half the cases. The tests with highest sensitivity
      included: a negative tuberculin skin test (100%), an elevated CD4/CD8 ratio in
      the BALF (100%), radiographic evidence of sarcoidosis on chest CT (79%) and brain
      MRI (80%). Other factors contributing to the diagnosis were: female gender (83%),
      age over 40 (67%), arthralgia (41%), asthenia (50%), vitritis (67%) and
      multifocal choroiditis (30%). In our study, treatment with corticosteroids
      resulted in significant improvement in over 80% of patients.

PMID- 23545337
TI  - [Features of the electronic eikonometer for the study of binocular function].
AB  - After presenting the components of this electronic eikonometer (device schematic
      and organizational chart) for the analysis and measurement of perceptive effects
      of binocular disparity, we review the specifics (tests with incorporated
      magnifications seen in polarized light) and the advantages of this device as
      compared to existing eikonometers (absence of any intermediary optical system).
      We provide a list of available tests in the test library and their parametric
      characteristics: Ogle Spatial Test for Aniseikonia, Fixation Disparity Test:
      binocular nonius, and Linear and Random stereoscopic tests. We develop a
      methodology adapted to each type of test and the manipulations to be performed by
      the operators and observers. We then provide some results of examinations
      performed with this eikonometer for a sample of observers equipped with glasses,
      contact lenses or implants. We propose an analysis of these various perceptive
      effects from experimental and theoretical studies: association between Depth,
      Disparity and Fusion; brief review of theoretical studies by automatic matrix
      calculus of retinal image size for various types of eyes: emmetropic and
      isometropic eyes based on various dioptric elements from Gullstrand's eye, axial
      anisometropia, anisometropia of conformation, aphakia resulting from these
      various eyes. We demonstrate the role of these studies in the analysis of
      subjective measurements of aniseikonia and for the choice of best correction:
      variations in amplitude and sign of the monocular components of the fixation
      disparity as a function of the viewing distance, Complexity of depth perception,
      according to the test used. Considering the evolution of the technology used for
      the realization of this prototype, we propose that this eikonometer be updated,
      in particular by using high-resolution flat screens, which would allow
      improvement and enrichment of the test library (definition, contrast and size of
      the observed images).

PMID- 23545338
TI  - Histamine 4 receptor plays an important role in auto-antibody-induced arthritis.
AB  - Rheumatoid arthritis is a widespread autoimmune disease. In the murine K/B*N
      arthritis model, anti-GPI (anti-glucose 6-phosphate isomerase) antibodies lead to
      the formation of immune complexes. In the course of pathogenesis, these complexes
      activate the immune system and induce degranulation of mast cells, which are
      essential in this model of rheumatoid arthritis. A major mediator in mast cell
      granules is histamine, which is proven to be indispensable for joint inflammation
      in K/B*N mice. Histamine is known to bind to four different receptors (HR1-4),
      which have different expression profiles and exert a variety of different
      functions, including activation of the immune system. To analyze the contribution
      of the different histamine receptors, we employed histamine receptor antagonists
      (cetirizine, ranitidine, thioperamide and clozapine) blocking the receptors in
      C57BL/6 mice. Arthritis was induced via K/B*N serum injection. The results
      demonstrated that mice treated with all four histamine receptor antagonists
      simultaneously showed no arthritic symptoms, while positive control mice injected
      with K/B*N serum and vehicle suffered from severe symptoms. When antagonists
      specific for HR1-4 were applied individually, only the HR4 antagonist clozapine
      could protect mice from arthritis, reflecting its expression and functionality in
      the immune system. 

PMID- 23545340
TI  - Validation of an educational booklet targeted to patients candidate for total
      knee arthroplasty.
AB  - BACKGROUND: Knee osteoarthritis is a highly prevalent condition and the leading
      reason for total knee arthroplasty (TKA). No consensus exists about the optimal
      content of preoperative patient information and, to the best of our knowledge, no
      validated information document is available. Our objective here was to obtain
      validation by healthcare professionals and patients of an educational booklet for
      patients awaiting TKA. MATERIALS AND METHODS: The booklet was developed and
      validated in six phases: systematic literature review, drafting of the first
      version, critical revision by a panel of experts, modification of the booklet,
      validation by a multidisciplinary panel of experts, and validation by two groups
      of patients, one composed of patients awaiting TKA and the other of patients in
      the immediate post-TKA period. We assessed the impact of the booklet based on
      knowledge and belief scores before and 2 days after receiving the booklet.
      RESULTS: Critical revision of the first draft led to changes to meet the concerns
      voiced by the experts. Knowledge improved only in the patient group given the
      booklet preoperatively (from 6/10 to 9/10, P=0.005). The booklet did not modify
      beliefs in either patient group. DISCUSSION: We used a rigorous methodology to
      develop and validate the contents of an educational booklet. Receiving this
      document before TKA resulted in improved patient knowledge but had no impact on
      beliefs. LEVEL OF EVIDENCE: Level IV.

PMID- 23545341
TI  - Differential effects of metal contamination on the transcript expression of
      immune- and stress-response genes in the Sydney Rock oyster, Saccostrea
      glomerata.
AB  - Environmental contamination by metals is a serious threat to the biological
      sustainability of coastal ecosystems. Our current understanding of the potential
      biological effects of metals in these ecosystems is limited. This study tested
      the transcriptional expression of immune- and stress-response genes in Sydney
      Rock oysters (Saccostrea glomerata). Oysters were exposed to four metals
      (cadmium, copper, lead and zinc) commonly associated with anthropogenic pollution
      in coastal waterways. Seven target genes (superoxide dismutase, ferritin,
      ficolin, defensin, HSP70, HSP90 and metallothionein) were selected. Quantitative
      (real-time) PCR analyses of the transcript expression of these genes showed that
      each of the different metals elicited unique transcriptional profiles.
      Significant changes in transcription were found for 18 of the 28 combinations
      tested (4 metals * 7 genes). Of these, 16 reflected down-regulation of gene
      transcription. HSP90 was the only gene significantly up-regulated by metal
      contamination (cadmium and zinc only), while defensin expression was
      significantly down-regulated by exposure to all four metals. This inhibition
      could have a significant negative effect on the oyster immune system, promoting
      susceptibility to opportunistic infections and disease.

PMID- 23545339
TI  - Notch signaling in pancreatic cancer: oncogene or tumor suppressor?
AB  - The Notch signaling pathways are known to play critical roles during pancreatic
      development, but it remains unclear what functions are important in the adult
      organ. One area of debate is the role of Notch signaling in the development of
      pancreatic ductal adenocarcinoma (PDAC) and proposed precursor lesions,
      pancreatic intraepithelial neoplasia (PanIN). Initial studies revealed that Notch
      signaling is reactivated during PDAC initiation and development, suggesting that
      Notch promotes PDAC and may therefore represent a target for drug development.
      However, more recent work reveals a tumor suppressive role for Notch receptors in
      the context of PanIN development. Here, we summarize the current literature
      describing Notch signaling in the development of PDAC, and discuss the potential
      of the Notch pathway as a therapeutic target.

PMID- 23545342
TI  - The impact of aluminium smelter shut-down on the concentration of fluoride in
      vegetation and soils.
AB  - Although a great deal is known about the deposition of fluoride on vegetation,
      and the hazards associated with uptake by grazing herbivores, little is known
      about what happens to the concentration of fluoride in vegetation and soil at
      polluted sites once deposition ceases. The closure of Anglesey Aluminium Metals
      Ltd smelter, in September 2009, provided a unique opportunity to study fluoride
      loading once deposition stopped. Fluoride was monitored in plants and soil within
      1 km of the former emission source. Fluoride concentrations in a range of plant
      material had decreased to background levels of 10 mg F kg(-1) after 36 weeks.
      Concentrations of fluoride in mineral-rich soils decreased steadily demonstrating
      their limited potential to act as contaminating sources of fluoride for forage
      uptake. There were significant differences in the rate of decline of fluoride
      concentrations between plant species.

PMID- 23545343
TI  - Reclamation of copper-contaminated soil using EDTA or citric acid coupled with
      dissolved organic matter solution extracted from distillery sludge.
AB  - Soil washing using a strong chelating agent is a common practice for restoring
      contaminated soils, but significant soil fertility degradation and high operation
      costs are the major disadvantages. Washing soil with a dissolved organic matter
      (DOM) solution has been identified as a method that can moderate the loss of
      nutrients in the soil and enhance metal removal. The DOM solutions were extracted
      from waste sludge obtained from a local whisky distillery. Single chelating
      washing and chelate-DOM washing were carried out using ethylenediaminetetraacetic
      acid (EDTA), citric acid, and DOM solutions to remediate highly Cu-contaminated
      soil. Two-phase washing using 0.34 M citric acid and then 1500 mg L(-1) DOM
      solution (pH 8.5) was found to be most favorable for the soil. With this
      treatment, 91% Cu was removed from the topsoil; the organic matter, cation
      exchange capacity, plant-available nitrogen, and available phosphate content
      increased by 28.1%, 103%, 17.7%, and 422%, respectively.

PMID- 23545344
TI  - Sex- and age-related differences of myocardial perfusion at rest assessed with
      multidetector computed tomography.
AB  - BACKGROUND: The clinical presentation of ischemic heart disease in women differs
      from men, which could reflect sex-related differences of normal physiology.
      Cardiac CT angiography provides a noninvasive method to assess both regional and
      transmural myocardial perfusion in addition to coronary atherosclerosis.
      OBJECTIVE: The aim of this study was to evaluate potential sex-related
      differences of (1) left ventricular (LV) myocardial perfusion measured as LV
      myocardial attenuation density/LV blood pool attenuation density (MyoAD-ratio) at
      rest and (2) transmural perfusion ratio (TPR) as a measure of endocardial
      perfusion relative to epicardial perfusion. METHODS: Myocardial perfusion at rest
      and coronary artery atherosclerosis were evaluated with multidetector CT in 206
      asymptomatic women and 203 age-matched men from the Copenhagen General Population
      Study. RESULTS: LV myocardial perfusion at rest (LV MyoAD-ratio) was higher in
      women than in men (9% difference; P = 0.039). In a multivariable analysis,
      including age, sex, cardiovascular risk factors, Agatston score, and presence of
      coronary stenosis, global LV MyoAD-ratio remained significantly higher in women
      than in men (P = 0.045). No effect of cardiovascular risk factors on myocardial
      perfusion at rest was noted. Myocardial perfusion at rest was correlated to age
      in men (r = 0.15, P = 0.031) but not in women (r = -0.01, P = 0.83). TPR was
      slightly lower in women than in men (1.12 vs 1.14; P = 0.0019). CONCLUSION: LV
      myocardial perfusion at rest is higher in women than men independent of coronary
      atherosclerosis in asymptomatic subjects with risk factors.

PMID- 23545345
TI  - Perioperative anesthetic and surgical complications of the Nuss procedure.
AB  - OBJECTIVE: The Nuss procedure is a chest wall remodeling surgery performed in
      patients with pectus excavatum. This study was performed to analyze perioperative
      surgical and anesthetic complications with the Nuss procedures. DESIGN: A
      retrospective analysis. SETTING: An academic hospital. PARTICIPANTS: Two hundred
      fourteen patients (children, adolescents, and adults) undergoing the Nuss
      procedure over 6 years. INTERVENTIONS: Patient age and sex, premorbid diseases,
      indications for surgery, patient position during the procedure, the length of
      surgery, time to hospital discharge, postoperative analgesia method, and the
      presence of perioperative complications were recorded. MEASUREMENTS: No mortality
      was observed. The overall complication rate was 18.7%, but the overall event rate
      was 42.6% (91 events in 40 patients). Intraoperative hypotension, tachycardia,
      and hypercapnia were the most common complications (4.7%), followed by
      postoperative ileus (3.2%), pneumothorax (right, left, or bilateral; 4.2%), lung
      parenchymal laceration (2.3%), and postoperative nausea and vomiting (2.3%). Two
      patients had an ulnar nerve palsy and 1 patient had a brachial nerve palsy as a
      result of surgical position. CONCLUSION: Although the Nuss procedure is reported
      to be minimally invasive, some serious complications concerning both surgery and
      anesthesia should not be overlooked.

PMID- 23545346
TI  - Low-dose spinal morphine for post-thoracotomy pain: a prospective randomized
      study.
AB  - OBJECTIVE: To compare the results of 0.2 mg and 0.3 mg of spinal morphine in
      patients with post-thoracotomy pain. DESIGN: A prospective, randomized, double
      blind study. SETTING: A university hospital and a tertiary referral center.
      PARTICIPANTS: Forty patients undergoing thoracotomy for lung resection.
      INTERVENTIONS: Spinal morphine: 0.2 mg or 0.3 mg. METHODS AND MAIN RESULTS:
      Patients were randomly allocated to receive either 0.2 mg or 0.3 mg of spinal
      morphine for post-thoracotomy pain prior to general anesthesia. Cumulative 24-
      and 48-hour intravenous patient-controlled analgesia meperidine consumption and
      numeric rating scale score for pain were recorded. The severity score (4-point
      scale) of sedation, nausea, vomiting, and pruritus was assessed for interval
      during the postoperative period. The times to first
      drinking/eating/sitting/walking were recorded. There was no statistically
      significant difference in 24-hour postoperative meperidine usages between the 2
      groups, which were 110 (interquartile range 90-180) and 95 (interquartile range
      57.5-175) mg, respectively. The median pain free times, time to first drinking,
      eating, sitting, and walking showed no differences between the 2 groups. The
      numeric rating scale score for pain and incidences of side effects were not
      different between the 2 groups. One patient who received 0.3 mg of spinal
      morphine developed respiratory acidosis with a respiratory rate of 10 per minute
      at 44 minutes after extubation. CONCLUSIONS: In patients who underwent elective
      thoracotomy, 0.2 mg of spinal morphine was as effective as 0.3 mg. Increasing the
      dosage of spinal morphine does not decrease postoperative meperidine consumption,
      but may lead to respiratory depression in rare cases.

PMID- 23545347
TI  - Effects of high-dose ulinastatin on inflammatory response and pulmonary function
      in patients with type-A aortic dissection after cardiopulmonary bypass under deep
      hypothermic circulatory arrest.
AB  - OBJECTIVES: To investigate effects of high-dose ulinastatin on the release of
      proinflammatory cytokines and lung injury in patients with aortic dissection
      after cardiopulmonary bypass (CPB) under deep hypothermic circulatory arrest
      (DHCA). DESIGN: A prospective, randomized and double-blinded study. SETTING: A
      teaching hospital. PARTICIPANTS: Thirty-six patients with acute type-A aortic
      dissection undergoing cardiac surgery using CPB under DHCA. INTERVENTIONS: These
      patients randomly were selected to received total doses of 20,000 units/kg of
      ulinastatin (n = 18) or 0.9% saline (control, n = 18) at 3 time points (after
      anesthetic induction, before aortic cross-clamp, and after aortic cross-clamp
      release). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor-alpha, interleukin
      6, interleukin 8 and polymorphonuclear neutrophil elastase (PMNE) were measured
      after anesthetic induction (T0), 30 minutes (T1) after aortic cross-clamp, 3
      (T2), 6 (T3) and 9 (T4) hours after weaning from CPB. Except for T1, pulmonary
      data, such as alveolar-arterial oxygen pressure difference, physiologic
      deadspace, peak inspiratory pressure, plateau pressure, static compliance and
      dynamic compliance, were obtained at the same time points. Concentrations of
      cytokines and PMNE were significantly lower in the ulinastatin group than the
      control group from T1 to T4, and peaked at T2 between the 2 groups. Compared with
      the pulmonary data of the control group at T2~T4, postoperative alveolar-arterial
      oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, and
      plateau pressure significantly were lower, and static compliance and dynamic
      compliance higher in the ulinastatin group. Significantly shorter intubation time
      and intensive care unit stay were found in the ulinastatin group. CONCLUSIONS:
      High-dose ulinastatin attenuates the elevation of cytokines and PMNE, reduces the
      pulmonary injury and improves the pulmonary function after CPB under DHCA.
      Consequently, it shortens the time of intubation and intensive care unit stay.

PMID- 23545348
TI  - Species differences in the neuromuscular activity of post-synaptic neurotoxins
      from two Australian black snakes (Pseudechis porphyriacus and Pseudechis
      colletti).
AB  - Bites by Australian black snakes (Pseudechis spp.) do not cause neurotoxicity in
      human envenoming. This is unusual as in vitro neurotoxicity has been reported for
      all Pseudechis spp. venoms. The present study aimed to identify, isolate and
      characterise neurotoxins from the venoms of Pseudechis porphyriacus and
      Pseudechis colletti to elucidate the reason for the lack of neurotoxicity in
      humans. alpha-Elapitoxin-Ppr1 and alpha-elapitoxin-Pc1 were isolated from P.
      porphyriacus and P. colletti, respectively, using reverse-phase high performance
      liquid chromatography. Each toxin consisted of 62 amino acids with molecular
      weights of 6746.5Da and 6759.6Da, respectively. alpha-Elapitoxin-Ppr1 and alpha
      elapitoxin-Pc1 caused concentration-dependent (0.1-0.3MUM) inhibition of indirect
      twitches in the chick biventer cervicis nerve-muscle preparation. Both toxins
      inhibited contractile responses to exogenous ACh and CCh, but not KCl, suggesting
      a post-synaptic mode of action at the nicotinic acetylcholine receptor (nAChR).
      CCh concentration-response curves obtained in the presence or absence of alpha
      elapitoxin-Ppr1 or alpha-elapitoxin-Pc1 indicated pA2 values of 6.97+/-0.03 and
      7.04+/-0.07, respectively. Neither alpha-elapitoxin-Ppr1 (0.1MUM) nor alpha
      elapitoxin-Pc1 (0.1MUM) had a significant effect on the electrically-induced
      twitches of the rat isolated phrenic nerve-diaphragm preparation. When the venom
      with the toxin removed (10MUg/ml) was added to both the rat and chick
      preparations, the inhibition was significantly less than that caused by the
      intact whole venoms (10MUg/ml). The current study shows that alpha-elapitoxin
      Ppr1 and alpha-elapitoxin-Pc1 act as pseudo-irreversible antagonists at the nAChR
      of the skeletal neuromuscular junction and that the avian preparation is more
      sensitive to the neurotoxic effects of these toxins than the mammalian
      preparation.

PMID- 23545349
TI  - Increasing exposure to antibody-stimulating proteins and polysaccharides in
      vaccines is not associated with risk of autism.
AB  - OBJECTIVE: To evaluate the association between autism and the level of
      immunologic stimulation received from vaccines administered during the first 2
      years of life. STUDY DESIGN: We analyzed data from a case-control study conducted
      in 3 managed care organizations (MCOs) of 256 children with autism spectrum
      disorder (ASD) and 752 control children matched on birth year, sex, and MCO. In
      addition to the broader category of ASD, we also evaluated autistic disorder and
      ASD with regression. ASD diagnoses were validated through standardized in-person
      evaluations. Exposure to total antibody-stimulating proteins and polysaccharides
      from vaccines was determined by summing the antigen content of each vaccine
      received, as obtained from immunization registries and medical records. Potential
      confounding factors were ascertained from parent interviews and medical charts.
      Conditional logistic regression was used to assess associations between ASD
      outcomes and exposure to antigens in selected time periods. RESULTS: The aOR (95%
      CI) of ASD associated with each 25-unit increase in total antigen exposure was
      0.999 (0.994-1.003) for cumulative exposure to age 3 months, 0.999 (0.997-1.001)
      for cumulative exposure to age 7 months, and 0.999 (0.998-1.001) for cumulative
      exposure to age 2 years. Similarly, no increased risk was found for autistic
      disorder or ASD with regression. CONCLUSION: In this study of MCO members,
      increasing exposure to antibody-stimulating proteins and polysaccharides in
      vaccines during the first 2 years of life was not related to the risk of
      developing an ASD.

PMID- 23545350
TI  - Pediatric cutaneous bleach burns.
AB  - Bleach is a common household product which can cause caustic injuries. Its
      effects on mucosal tissues and the eye have been well-described in the
      literature. However, there is little information published regarding the
      appearance and effect of bleach on a child's skin. We report three children who
      sustained chemical burns after contact with bleach. All three children sustained
      accidental bleach burns while at home, and each child had a distinct brown
      discoloration to the skin from the injury. All three children had treatment and
      follow-up for their burns. Two of the children sustained more severe burns, which
      were extensive and required more time to heal. There was also long-term scarring
      associated with the severe burns. Like most burns, pain control is required until
      the injury heals. 

PMID- 23545351
TI  - Bullying vs. school violence: a response to Williams and Stelko-Pereira (2013).

PMID- 23545352
TI  - A case series of twenty one maternal filicides in the UK.
AB  - OBJECTIVE: This study reports a case-series study of 21 women from the United
      Kingdom convicted of the murder or manslaughter of their child (maternal
      filicide: MF). These cases were reviewed using data provided from police forces
      and from publicly available resources. METHODS: Content and thematic analysis and
      multidimensional scaling techniques were used to analyse the relationships
      between the variables present in the commission of the crimes. RESULTS: Mothers
      who killed their children could be categorised as emotionally driven and in
      despair at their situation, or rejecting their children due to perceiving them as
      a threat. Mothers who killed their babies (neonaticides) appeared to form two
      distinct subgroups: reluctant and detached neonaticidal offenders. CONCLUSION:
      These findings offer an insight into the factors that may be of relevance in
      understanding how a mother may come to commit MF, and are interpreted in terms of
      disturbed attachment processes.

PMID- 23545353
TI  - Disruption of the intestinal mucosal barrier in Candida albicans infections.
AB  - Candida albicans is a common microorganism in the intestine. However, invasive C.
      albicans infection has emerged as a life-threatening disease in recent years. The
      mortality rate of invasive candidiasis is high in critically ill hosts. C.
      albicans can switch from the yeast to the hyphal morphology, and take advantage
      of the impaired intestinal mucosal barrier and insufficient immunity of the host
      to facilitate its colonization and penetration. Despite the availability of
      potent new antifungal drugs in recent years, the treatment of severe candidiasis,
      especially candidaemia, has not been substantially improved. In this review, the
      virulence factors of C. albicans, as well as the antagonistic role of the
      intestinal mucosal barrier will be discussed to illuminate the mechanisms of C.
      albicans enterogenic infections.

PMID- 23545354
TI  - Isolation and identification of antifungal peptides from Bacillus BH072, a novel
      bacterium isolated from honey.
AB  - A bacterial strain BH072 isolated from a honey sample showed antifungal activity
      against mold. Based on morphological, biochemical, physiological tests, and
      analysis of 16S rDNA sequence, the strain was identified to be a new subspecies
      of Bacillus sp. It had a broad spectrum of antifungal activity against various
      mold, such as Aspergillus niger, Pythium, and Botrytis cinerea. Six pairs of
      antifungal genes primers were designed and synthesized, and ituA, hag, tasA genes
      were detected by PCR analysis. The remarkable antifungal activity could be
      associated with the co-production of these three peptides. One of them was
      purified by 30-40% ammonium sulfate precipitation, Sephadex G-75 gel filtration
      and anion exchange chromatography on D201 resin. The purified peptide was
      estimated to be 35.615 kDa and identified to be flagellin by micrOTOF-Q II. By
      using methanol extraction, another substance was isolated from fermentation
      liquor, and determined to be iturin with liquid chromatography-mass spectrometry
      (LC-MS) method. The third possible peptide encoded by tasA was not isolated in
      this study. The culture liquor displayed antifungal activity in a wide pH range
      (5.0-9.0) and at 40-100 degrees C. The result of the present work suggested that
      Bacillus BH072 might be a bio-control bacterium of research value.

PMID- 23545355
TI  - Isolation and characterization of a glyphosate-degrading rhizosphere strain,
      Enterobacter cloacae K7.
AB  - Plant-growth-promoting rhizobacteria exert beneficial effects on plants through
      their capacity for nitrogen fixation, phytohormone production, phosphate
      solubilization, and improvement of the water and mineral status of plants. We
      suggested that these bacteria may also have the potential to express degradative
      activity toward glyphosate, a commonly used organophosphorus herbicide. In this
      study, 10 strains resistant to a 10 mM concentration of glyphosate were isolated
      from the rhizoplane of various plants. Five of these strains--Alcaligenes sp. K1,
      Comamonas sp. K4, Azomonas sp. K5, Pseudomonas sp. K3, and Enterobacter cloacae
      K7--possessed a number of associative traits, including fixation of atmospheric
      nitrogen, solubilization of phosphates, and synthesis of the phytohormone indole
      3-acetic acid. One strain, E. cloacae K7, could utilize glyphosate as a source of
      P. Gas-liquid chromatography showed that E. cloacae growth correlated with a
      decline in herbicide content in the culture medium (40% of the initial 5mM
      content), with no glyphosate accumulating inside the cells. Thin-layer
      chromatography analysis of the intermediate metabolites of glyphosate degradation
      found that E. cloacae K7 had a C-P lyase activity and degraded glyphosate to give
      sarcosine, which was then oxidized to glycine. In addition, strain K7 colonized
      the roots of common sunflower (Helianthus annuus L.) and sugar sorghum (Sorghum
      saccharatum Pers.), promoting the growth and development of sunflower seedlings.
      Our findings extend current knowledge of glyphosate-degrading rhizosphere
      bacteria and may be useful for developing a biotechnology for the cleanup and
      restoration of glyphosate-polluted soils.

PMID- 23545356
TI  - Intra-arterial radioembolization of breast cancer liver metastases: a structured
      review.
AB  - Radioembolization using yttrium-90 microspheres (90Y-RE) is an emerging treatment
      option for breast cancer liver metastases (BCLM) patients if other locoregional
      and systemic treatment options fail. The purpose of this study was to provide a
      systematic overview of the current literature concerning 90Y-RE for BCLM
      patients. A systematic search for relevant articles was performed in MEDLINE,
      EMBASE, and The Cochrane Library (January 2012) by combining an extensive list of
      synonyms for the determinants 'radioembolization', 'yttrium-90' and 'microsphere'
      with synonyms for the domain 'liver'. Data on tumor response, survival and
      toxicity were extracted and collected from all relevant articles. The search
      yielded 4078 studies, of which six were finally included for analysis, concerning
      a total of 198 patients. Tumor response was scored in five studies using either
      RECIST (n=3) or WHO criteria (n=2). Overall disease control rates (complete
      response, partial response and stable disease) at 2-4 months post treatment
      ranged from 78% to 96%. Median survival, available in four studies, ranged from
      10.8 to 20.9 months. In total, gastric ulceration was reported in ten patients
      (5%) and treatment related mortality in three patients (2%). The results from the
      analyzed studies consistently show that 90Y-RE is a safe and effective treatment
      option for BCLM patients. Comparative studies, especially combining 90Y-RE with
      systemic therapy are strongly encouraged.

PMID- 23545357
TI  - Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models.
AB  - In the present study, we have investigated the anti-nociceptive and anti
      allodynic activity of the renin inhibitor, aliskiren, in various pain models. The
      anti-nociceptive activity of aliskiren was investigated in chemically-induced
      pain, orofacial pain and centrally mediated pain models. Anti-allodynic activity
      was evaluated in post-operative and neuropathic pain models. The levels of TNF
      alpha and IL-6 were measured in homogenates of hind paw as markers of
      inflammation in formalin injected mice. Intraperitoneal administration of
      aliskiren (1-50mg/kg) showed anti-nociceptive activity in the writhing test,
      formalin hind paw test, capsaicin induced pain, and orofacial pain tests in ICR
      mice in a dose dependent manner. Aliskiren (50mg/kg, i.p.) reduced levels of TNF
      alpha and IL-6 in hind paw homogenates of formalin-injected mice. Aliskiren
      (50mg/kg, i.p.) did not show any analgesic activity in hot-plate and tail-flick
      tests, indicating the absence of centrally mediated anti-nociceptive effects. On
      the other hand, intra-plantar administration of aliskiren (0.1, 0.5 and 1mg)
      showed analgesic activity in rat formalin tests, indicating a locally mediated
      effect. Aliskiren (30-100mg/kg, i.p.) showed anti-allodynic activity in post
      operative pain and chronic constriction injury-induced neuropathic pain in
      Sprague Dawley rats. This data suggests that aliskiren may have the potential to
      be used as an anti-nociceptive and anti-allodynic agent.

PMID- 23545358
TI  - Current approaches for neoadjuvant chemotherapy in breast cancer.
AB  - Compared to adjuvant chemotherapy, the administration of the same regimen in the
      neoadjuvant setting provides women with identical improvements in disease free
      and overall survival. Neoadjuvant chemotherapy may offer benefits to properly
      selected women such as broadening surgical options and enhancing the likelihood
      of breast conservation. Assessment of response to neoadjuvant chemotherapy
      provides women with an individualized estimate of prognosis. For example, a woman
      who achieves a complete pathological response following neoadjuvant chemotherapy
      has a very low risk of recurrence compared to a woman with similar tumor
      characteristics and a large residual disease. In this review we will provide a
      historical perspective and discuss the aims of neoadjuvant chemotherapy in
      primary operable breast cancer; as well as appropriate patient selection,
      treatment strategies, response monitoring, and postoperative care. We will also
      discuss the attractiveness of this approach to study the mechanism of action of
      standard and novel agents, and the role of predictive biomarkers of response to
      treatment and outcomes. 

PMID- 23545359
TI  - Molecular imaging for monitoring treatment response in breast cancer patients.
AB  - Currently, tumour response following drug treatment is based on measurement of
      anatomical size changes. This is often done according to Response Evaluation
      Criteria in Solid Tumours (RECIST) and is generally performed every 2-3 cycles.
      Bone metastases, being the most common site of distant metastases in breast
      cancer, are not measurable by RECIST. The standard response measurement provides
      no insight in changes of molecular characteristics. In the era of targeted
      medicine, knowledge of specific molecular tumour characteristics becomes more
      important. A potential way to assess this is by means of molecular imaging.
      Molecular imaging can visualise general tumour processes, such as glucose
      metabolism with (18)F-fluorodeoxyglucose ((18)F-FDG) and DNA synthesis with (18)F
      fluorodeoxythymidine ((18)F-FLT). In addition, an increasing number of more
      specific targets, such as hormone receptors, growth factor receptors, and growth
      factors can be visualised. In the future molecular imaging may thus be of value
      for personalised treatment-selection by providing insight in the expression of
      these drug targets. Additionally, when molecular changes can be detected early
      during therapy, this may serve as early predictor of response. However, in order
      to define clinical utility of this approach results from (ongoing) clinical
      trials is required. In this review we summarise the potential role of molecular
      imaging of general tumour processes as well as hormone receptors, growth factor
      receptors, and tumour micro-environment for predicting and monitoring treatment
      response in breast cancer patients.

PMID- 23545360
TI  - Discrepancy between routine and expert pathologists' assessment of non-palpable
      breast cancer and its impact on locoregional and systemic treatment.
AB  - Histopathological parameters are essential for deciding on adjuvant treatment
      following breast cancer surgery. We assessed the impact of inter-observer
      variability on treatment strategy in patients operated for clinically node
      negative, non-palpable breast carcinomas. In the context of a multicenter
      randomised controlled trial, clinical and histological data of 310 patients with
      clinically node negative non-palpable invasive breast cancer were prospectively
      collected. Histological assessment of the primary tumour and sentinel nodes was
      first performed in a routine setting, subsequently central review took place. In
      case of discordance between local en central assessments, we determined the
      impact on locoregional and systemic treatment strategy. Discordance between local
      and central review was observed in 13% of the patients for type (kappa 0.60, 95%
      CI 0.50-0.71), in 12% for grade (k=0.796, 95% CI 0.73-0.86), in 1% for ER status
      (k=0.898, 95% CI 0.80-1.0), in 2% for PR status (k=0.940 95% CI 0.89-0.99).
      Discrepancy in the assessment of the sentinel node(s) was seen in 2% of the
      patients (k=0.954, 95% CI 0.92-0.98). Applying current Dutch Guidelines, central
      review would have affected locoregional treatment in 2% (7/310), systemic
      treatment in 5% (16/310) and both in 1% (2/310) of the patients. For the 9 (3%)
      patients in whom central review would have led to additional systemic treatment,
      Adjuvant! predicted 10 years mortality and recurrence rate would have decreased
      with a median of 4.6% and 15%, respectively. Discordance between routine
      histological assessment and central review of non-palpable breast carcinoma
      specimens and sentinel nodes was observed in 24% of patients. This inter-observer
      variation would have impacted locoregional and/or systemic treatment strategies
      in 8% of the patients. 

PMID- 23545361
TI  - Denosumab in breast cancer treatment.
AB  - The bone is the most common site to which breast cancer metastasises. Recently,
      denosumab, a fully human monoclonal antibody that binds to receptor activator of
      nuclear factor kappa-B ligand (RANKL) has been developed as a new targeted bone
      therapy. In a large randomized phase III study with a head-to-head comparison of
      denosumab to zoledronic acid in patients with bone metastases of breast cancer,
      denosumab significantly delayed the time to first skeletal related event. In the
      adjuvant setting denosumab significantly increased bone mineral density compared
      to placebo in a phase III study in patients treated with aromatase inhibitors.
      Preclinical data suggest an effect of denosumab on tumour growth and even on
      carcinogenesis. This review describes the current indications for denosumab in
      the various settings of breast cancer treatment, with special attention for
      efficacy, short and long term toxicity and other relevant issues for clinical
      practice. Furthermore possible and necessary future research questions are
      proposed.

PMID- 23545362
TI  - Treatment of breast cancer brain metastases.
AB  - Breast cancer represents the second most frequent cause of brain metastases.
      Treatment planning should consider several tumor and patient factors to estimate
      prognosis based on the Karnofsky Performance Status (KPS), age, extent of extra
      cerebral disease as well as genetic subtype. When systemic disease is under
      control patients with up to three metastases qualify for local therapy, such as
      surgical excision or stereotactic radiotherapy. After the local treatment the
      addition of whole brain radiation therapy may be postponed until disease
      progression in the brain is observed and overall survival will not be
      compromised. Asymptomatic brain metastases may be first approached with a
      systemic treatment to which the primary tumor is considered to be sensitive. 

PMID- 23545363
TI  - Novel strategies towards the use of anti-angiogenic agents in breast cancer.
AB  - Angiogenesis is essential for tumor growth and development of metastases in human
      breast cancer. Currently, bevacizumab (inhibitor of VEGF) is the most extensively
      studied agent in clinical trials. However, only modest improvement of overall
      survival and response rates is seen in these trials and the use of anti
      angiogenic agents in breast cancer is still controversial. It is of crucial
      importance to identify patients that respond to anti-angiogenic agents. Whether
      triple negative and BRCA1-related tumors are more sensitive to these type of
      agents should be further explored. In addition, we believe that treatment with
      anti-angiogenic agents could also be improved by optimizing treatment schedules
      and combinations. 

PMID- 23545364
TI  - An update on male breast cancer and future directions for research and treatment.
AB  - Male breast cancer is a rare disease for which treatment has been based on the
      evidence available from female breast cancer. The new genomic tools can better
      characterize the biology of breast cancer. It is hoping that these will help to
      clarify possible differences of breast cancer behaviour in male patients, which
      will have a major impact on treatment strategies and on the conduct of clinical
      trials in this setting. In this review we will summarize available information on
      epidemiology, risk factors for breast cancer in men, the new insights of the
      biology of this disease, current recommendations for treatment and insights for
      future research. 

PMID- 23545365
TI  - Tamoxifen resistance: from bench to bedside.
AB  - Although tamoxifen is a classical example of a targeted drug, a substantial
      proportion of estrogen receptor alpha positive breast cancer patients does not
      benefit from the drug. Over the last few decades, many potential biomarkers have
      been discovered in cell biological studies that may aid in the prediction of
      tamoxifen sensitivity and guide in treatment selection. Nonetheless, the
      transition of such a biomarker from the scientific community towards a diagnostic
      test that can be used in daily clinical practice has been far from ideal, and
      such markers seldom face clinical introduction. From a large number of potential
      predictive biomarkers as described in cell biological literature, the clinical
      (translational) scientist has to make a decision which of these biomarkers should
      be tested in clinical material to determine their clinical validity. This problem
      is not trivial, since patient samples with clinical follow-up are a valuable
      asset that should therefore be cherished. In this review, we will describe a
      number of 'cell biological biomarkers' for tamoxifen resistance and their
      possible clinical implications. This may guide the clinical scientist in choosing
      what potential biomarkers to test on tumour samples, which may catalyse the
      translation of scientific discoveries into daily clinical practice of breast
      cancer medicine.

PMID- 23545366
TI  - Dengue virus neutralization and antibody-dependent enhancement activities of
      human monoclonal antibodies derived from dengue patients at acute phase of
      secondary infection.
AB  - Public health concern about dengue diseases, caused by mosquito-borne infections
      with four serotypes of dengue virus (DENV-1-DENV-4), is escalating in tropical
      and subtropical countries. Most of the severe dengue cases occur in patients
      experiencing a secondary infection with a serotype that is different from the
      first infection. This is believed to be due to antibody-dependent enhancement
      (ADE), by which one DENV serotype uses pre-existing anti-DENV antibodies elicited
      in the primary infection to facilitate entry of a different DENV serotype into
      the Fc receptor-positive macrophages. Recently, we prepared a number of
      hybridomas producing human monoclonal antibodies (HuMAbs) by using peripheral
      blood lymphocytes from Thai patients at acute phase of secondary infection with
      DENV-2. Here, we characterized 17 HuMAbs prepared from two patients with dengue
      fever (DF) and one patient with dengue hemorrhagic fever (DHF) that were selected
      as antibodies recognizing viral envelope protein and showing higher
      neutralization activity to all serotypes. In vivo evaluation using suckling mice
      revealed near perfect activity to prevent mouse lethality following intracerebral
      DENV-2 inoculation. In a THP-1 cell assay, these HuMAbs showed ADE activities
      against DENV-2 at similar levels between HuMAbs derived from DF and DHF patients.
      However, the F(ab')2 fragment of the HuMAb showed a similar virus neutralization
      activity as original, with no ADE activity. Thus, these HuMAbs could be one of
      the therapeutic candidates against DENV infection.

PMID- 23545367
TI  - Attenuation of arsenic retention by resveratrol in lung of arsenic trioxide
      exposed rats.
AB  - Arsenic trioxide (As2O3) is an important environmental toxin. In this study, the
      effect of resveratrol on As2O3-induced lung injury in rats is evaluated. The
      results showed that pre-treatment with resveratrol protected As2O3-induced lung
      injury by the maintenance of glutathione redox system and decrease in arsenic
      retention. These suggest supplement with resveratrol may alleviate lung injury in
      the individuals with chronic exposure to arsenic.

PMID- 23545369
TI  - Melanoma death prevention: moving away from the sun.
AB  - This evidence-backed editorial addresses the limitations of solely primary
      prevention campaigns and outlines the proven efficacy of early
      detection/secondary prevention strategies with respect to melanoma. It
      synthesizes experience from several outreach efforts that have resulted in
      sustained improvements in knowledge and self-skin examination behaviors. Data
      demonstrate that educational campaigns emphasizing increased knowledge about
      melanoma and self-screening practices correlate with thinner tumors. The
      editorial also confronts the lack of data around skin cancer screening per the US
      Preventative Services Task Force. It explains how we might address the issue to
      obtain solid evidence to back a recommendation for screening of high-risk
      populations in the future. Cost-efficacy of skin cancer screening is also
      addressed. Lastly, lessons learned from other cancers, particularly breast
      cancer, with respect to successful educational campaign creation and development
      of an effective cause marketing campaign for advocacy are discussed. Hypothetical
      ideas for a screening algorithm and for educational/media campaigns are presented
      with the hope of triggering thoughtful discussion and forward momentum.

PMID- 23545368
TI  - Inner ear supporting cells: rethinking the silent majority.
AB  - Sensory epithelia of the inner ear contain two major cell types: hair cells and
      supporting cells. It has been clear for a long time that hair cells play critical
      roles in mechanoreception and synaptic transmission. In contrast, until recently
      the more abundant supporting cells were viewed as serving primarily structural
      and homeostatic functions. In this review, we discuss the growing information
      about the roles that supporting cells play in the development, function and
      maintenance of the inner ear, their activities in pathological states, their
      potential for hair cell regeneration, and the mechanisms underlying these
      processes. 

PMID- 23545370
TI  - A prospective observational study evaluating hypothalamic-pituitary-adrenal axis
      alteration and efficacy of intramuscular triamcinolone acetonide for steroid
      responsive dermatologic disease.
AB  - BACKGROUND: The lack of recommendations regarding dosing and administration, an
      undetermined risk of hypothalamic-pituitary-adrenal axis alteration, and the
      unknown effectiveness of intramuscular (IM) corticosteroid injection to treat
      dermatologic disease may be deterrents to use. OBJECTIVE: We sought to evaluate
      presence and duration of iatrogenic Cushing syndrome and secondary adrenal
      insufficiency in patients receiving IM triamcinolone acetonide (TAC), and to
      assess physician- and patient-reported outcomes. METHODS: We conducted a
      prospective observational study of 14 patients given the diagnosis of steroid
      responsive dermatologic disease who received either 1 or 2 doses 6 weeks apart of
      IM TAC. Baseline and follow-up cortisol, adrenocorticotropic hormone, Physician
      and Subject Global Assessments of Disease Activity Scale score, and the visual
      analog scale score of pruritus were evaluated at 6-week intervals. RESULTS:
      Although mean total cortisol was significantly decreased at 6 and 12 weeks
      compared with baseline, IM TAC did not result in iatrogenic Cushing syndrome or
      secondary adrenal insufficiency in any patient. Mean Physician and Subject Global
      Assessments of Disease Activity Scale scores were significantly improved at 6 and
      12 weeks compared with baseline. Mean visual analog scale pruritus scores were
      significantly improved at 6 weeks compared with baseline. LIMITATIONS: The study
      was limited by the cohort size and a lack of a comparator group. CONCLUSION: IM
      TAC appears safe when administered as 2 injections at 6-week intervals.
      Significant improvement was noted across a number of steroid-responsive
      dermatoses. These results may provide a guide to dosing, frequency, and
      administration for dermatologists considering the use of IM TAC in the
      appropriate clinical contexts.

PMID- 23545371
TI  - Influence of "GERD" label on parents' decision to medicate infants.
AB  - BACKGROUND: The factors that drive overtreatment of gastroesophageal reflux
      disease (GERD) are not well understood, but it has been proposed that the use of
      the "GERD" disease label could perpetuate use of medication in otherwise healthy
      infants. METHODS: To determine if use of the disease label GERD influences
      parents' perceived need to medicate an infant, we surveyed parents in a general
      pediatric clinic. Parents were given a hypothetical clinical scenario describing
      an infant who cries and spits up excessively but is otherwise healthy. Using a 2
      * 2 factorial design, parents were randomized to receive a scenario in which the
      doctor either gave a diagnosis of GERD or did not provide a disease label;
      additionally, half of parents were told that existing medications are probably
      ineffective, whereas the rest were not given any effectiveness information. We
      measured parent interest in medication, perception of illness severity, and
      appreciation of medication offer. RESULTS: Parents who received a GERD diagnosis
      were interested in medicating their infant, even when they were told that the
      medications are likely ineffective. However, parents not given a disease label
      were interested in medication only when medication effectiveness was not
      discussed (and hence likely assumed). CONCLUSIONS: Labeling an otherwise healthy
      infant as having a "disease" increased parents' interest in medicating their
      infant when they were told that medications are ineffective. These findings
      suggest that use of disease labels may promote overtreatment by causing people to
      believe that ineffective medications are both useful and necessary.

PMID- 23545372
TI  - Guided self-help for the treatment of pediatric obesity.
AB  - BACKGROUND AND OBJECTIVE: Clinic-based programs for childhood obesity are not
      available to a large proportion of the population. The purpose of this study was
      to evaluate the efficacy of a guided self-help treatment of pediatric obesity
      (GSH-PO) compared with a delayed treatment control and to evaluate the impact of
      GSH-PO 6-months posttreatment. METHODS: Fifty overweight or obese 8- to 12-year
      old children and their parents were randomly assigned to immediate treatment or
      to delayed treatment. The GSH-PO includes 12 visits over 5 months and addresses
      key components included in more intensive clinic-based programs. Children and
      parents in the immediate treatment arm were assessed at time 1 (T1), participated
      in GSH-PO between T1 and T2, and completed their 6-month posttreatment assessment
      at T3. Children and parents in the delayed treatment arm were assessed at T1,
      participated in GSH-PO between T2 and T3, and completed their 6-month
      posttreatment assessment at T4. The main outcome measures were BMI, BMI z score,
      and percentage overweight (%OW). RESULTS: Children in the immediate treatment GSH
      PO arm decreased their BMI significantly more than did the delayed treatment arm
      (BMI group * time = -1.39; P < .001). Similar results were found for BMI z score
      and %OW. At the 6-month posttreatment assessment, changes resulting from GSH-PO
      were maintained for BMI z score and %OW but not BMI (BMI time effect = -0.06, not
      significant; BMI z score time effect = -0.10, P < .001; %OW time effect = -4.86,
      P < .05). CONCLUSIONS: The GSH-PO showed initial efficacy in decreasing BMI for
      children in this study. Additional efficacy and translational studies are needed
      to additionally evaluate GSH-PO.

PMID- 23545374
TI  - A new model to decrease time-to-appointment wait for gastroenterology evaluation.
AB  - OBJECTIVE: To describe the implementation and evaluation of a quality improvement
      intervention to increase new-patient access and decrease time-to-appointment wait
      for gastroenterology care. METHODS: We used a new model of care for
      gastroenterology evaluation. For specified clinical complaints, we offered new
      patient appointments that were scheduled with a general pediatrician as an
      alternative to a subspecialist. A nurse navigator assisted in triaging patients.
      We analyzed all patient encounters over an 8-month period. To verify decreased
      time-to-appointment wait, mystery shoppers made semimonthly calls to centralized
      scheduling. We surveyed parents/families after visits with the pediatrician or
      subspecialists regarding satisfaction. RESULTS: The "access" pediatrician
      evaluated and treated ~40% of all new patients presenting to the division during
      the study period. Approximately 10% of new patients evaluated by the pediatrician
      (4% overall) were referred on to the subspecialist; fewer patients were
      reevaluated by the pediatrician in follow-up. The pediatrician ordered a minimal
      number of procedures. Semimonthly sampling revealed that overall new-patient
      access improved from an average time-to-appointment wait of 25 days to <1 day.
      Parent/family satisfaction was high for the patients evaluated by the
      pediatrician. CONCLUSIONS: Embedding a general pediatrician within a subspecialty
      division, and navigating patients to this provider, can increase access to
      treatment of new low- to moderate-complexity patients. The access pediatrician
      can maintain patient satisfaction, provide high-quality care, and decrease need
      for subspecialist evaluation. The model, in the setting of a large academic
      medical center, may provide a solution for barriers to patient care such as
      lengthy time-to-appointment wait.

PMID- 23545373
TI  - Sexual initiation, contraceptive use, and pregnancy among young adolescents.
AB  - OBJECTIVE: To present new data on sexual initiation, contraceptive use, and
      pregnancy among US adolescents aged 10 to 19, and to compare the youngest
      adolescents' behaviors with those of older adolescents. METHODS: Using nationally
      representative data from several rounds of the National Survey of Family Growth,
      we performed event history (ie, survival) analyses to examine timing of sexual
      initiation and contraceptive use. We calculated adolescent pregnancy rates by
      single year of age using data from the National Center for Health Statistics, the
      Guttmacher Institute, and the US Census Bureau. RESULTS: Sexual activity is and
      has long been rare among those 12 and younger; most is nonconsensual. By
      contrast, most older teens (aged 17-19) are sexually active. Approximately 30% of
      those aged 15 to 16 have had sex. Pregnancy rates among the youngest teens are
      exceedingly low, for example, ~1 per 10 000 girls aged 12. Contraceptive uptake
      among girls as young as 15 is similar to that of their older counterparts,
      whereas girls who start having sex at 14 or younger are less likely to have used
      a method at first sex and take longer to begin using contraception. CONCLUSIONS:
      Sexual activity and pregnancy are rare among the youngest adolescents, whose
      behavior represents a different public health concern than the broader issue of
      pregnancies to older teens. Health professionals can improve outcomes for
      teenagers by recognizing the higher likelihood of nonconsensual sex among younger
      teens and by teaching and making contraceptive methods available to teen patients
      before they become sexually active.

PMID- 23545375
TI  - Interventions for preschool children at high risk for ADHD: a comparative
      effectiveness review.
AB  - OBJECTIVES: The US Agency for Healthcare Research and Quality sponsored a
      comparative effectiveness review of interventions for preschoolers at risk for
      attention-deficit/hyperactivity disorder (ADHD). METHODS: Medline, Cochrane
      CENTRAL, Embase, PsycInfo, and Education Resources Information Center were
      searched from 1980 to November 24, 2011. Selected studies were comparative, and
      enrolled children <6 years with clinically significant disruptive behavior,
      including ADHD. The interventions evaluated were parent behavior training (PBT),
      combined home and school/day care interventions, and methylphenidate use. Data
      were extracted by using customized software. Two independent raters evaluated
      studies as good, fair, or poor by using the Effective Public Health Practice
      Project Quality Assessment Tool for Quantitative Studies Risk of Bias. Overall
      strength of evidence (SOE) was rated for each intervention's effectiveness,
      accounting for study design, systematic error, consistency of results, directness
      of evidence, and certainty regarding outcome. RESULTS: Fifty-five studies were
      examined. Only studies examining PBT interventions could be pooled statistically
      using meta-analysis. Eight "good" studies examined PBT, total n = 424; SOE was
      high for improved child behavior, standardized mean difference = -0.68 (95%
      confidence interval: -0.88 to -0.47), with minimal heterogeneity among studies.
      Only 1 good study evaluated methylphenidate, total n = 114; therefore, SOE for
      methylphenidate was low. Combined home and school/day care interventions showed
      inconsistent results. The literature reported adverse effects for methylphenidate
      but not for PBT. CONCLUSIONS: With more studies consistently documenting
      effectiveness, PBT interventions have greater evidence of effectiveness than
      methylphenidate for treatment of preschoolers at risk for ADHD.

PMID- 23545377
TI  - Molluscum BOTE sign: a predictor of imminent resolution.
AB  - Molluscum contagiosum is a common self-limited viral skin infection. The course
      of the infection often includes tender, crusted, erythematous lesions that prompt
      suspicion for bacterial infection. However, these signs of inflammation represent
      a host response that often precedes resolution of the viral disease, rather than
      bacterial superinfection, and do not require additional antibacterial treatment.
      We present a case report and retrospective review of 7 additional cases to
      characterize the clinical presentation of inflamed molluscum, assess the
      utilization of medical resources, and consider the psychosocial burden associated
      with mistaken diagnoses of bacterial infection. We propose the acronym "BOTE"*
      sign (for beginning of the end) to help underscore the significance of
      inflammation as an expected variant in the evolution of molluscum immunity.

PMID- 23545378
TI  - The hazards of medicalizing variants of normal.

PMID- 23545379
TI  - Epidemiology and predictors of failure of the infant car seat challenge.
AB  - OBJECTIVES: The American Academy of Pediatrics recommends all neonates born at
      <37 weeks' gestation receive a predischarge Infant Car Seat Challenge (ICSC), a
      resource-intensive test with little information on failure rates and risk
      factors. We sought to determine incidence and predictors of failure to allow more
      selective testing. METHODS: We conducted a retrospective medical record review of
      1173 premature neonates qualifying for the ICSC between 2009 and 2010. We looked
      at ICSC result and potential risk factors and then performed bivariate and
      multivariable logistic analyses to evaluate for predictors of failure. RESULTS:
      Overall incidence of failure was 4.3%. Infants who failed were less premature and
      had higher birth weights. Late-preterm infants made up 60% of our study
      population but accounted for 78% of failures (P = .019). Infants who passed had
      older chronologic ages at time of testing, were more likely to have been exposed
      to caffeine, and were more likely to have required some type of respiratory
      support than those that failed. Final multivariable model demonstrated that
      increasing birth gestational age (GA) increased the odds of failure when
      corrected for gender, race, and small for GA status. For every 1-day increase in
      birth GA the odds ratio of failure was 1.03 (95% confidence interval 1.01-1.05).
      CONCLUSIONS: We found that increasing birth GA was a significant predictor of
      failure, and that late-preterm infants comprised a significant percentage of
      infants who failed. This suggests that limiting testing to extremely premature
      infants would miss most cases of ICSC failure.

PMID- 23545380
TI  - Long-term effectiveness of varicella vaccine: a 14-Year, prospective cohort
      study.
AB  - BACKGROUND: Varicella vaccine was licensed in the United States in 1995 for
      individuals >=12 months of age. A second dose was recommended in the United
      States in June 2006. Varicella incidence and vaccine effectiveness were assessed
      in a 14-year prospective study conducted at Kaiser Permanente Northern
      California. METHODS: A total of 7585 children vaccinated with varicella vaccine
      in their second year of life in 1995 were followed up prospectively for
      breakthrough varicella and herpes zoster (HZ) through 2009. A total of 2826 of
      these children received a second dose in 2006-2009. Incidences of varicella and
      HZ were estimated and compared with prevaccine era rates. RESULTS: In this cohort
      of vaccinated children, the average incidence of varicella was 15.9 per 1000
      person-years, nine- to tenfold lower than in the prevaccine era. Vaccine
      effectiveness at the end of the study period was 90%, with no indication of
      waning over time. Most cases of varicella were mild and occurred early after
      vaccination. No child developed varicella after a second dose. HZ cases were
      mild, and rates were lower in the cohort of vaccinated children than in
      unvaccinated children during the prevaccine era (relative risk: 0.61 [95%
      confidence interval: 0.43-0.89]). CONCLUSIONS: This study confirmed that
      varicella vaccine is effective at preventing chicken pox, with no waning noted
      over a 14-year period. One dose provided excellent protection against moderate to
      severe disease, and most cases occurred shortly after the cohort was vaccinated.
      The study data also suggest that varicella vaccination may reduce the risks of HZ
      in vaccinated children.

PMID- 23545381
TI  - Extremely low birth weight and infant mortality rates in the United States.
AB  - OBJECTIVE: Infant mortality rates (IMR) and neonatal mortality rates (NMR) in the
      United States have not decreased recently. The purpose of this study was to
      determine the contributions of birth weight and gestational age subgroups to the
      IMR and NMR in the United States. METHODS: We used the most recent (1983-2005) US
      linked birth and infant death data and simple regression analysis to determine
      the contributions of specific birth weight and gestational age subgroups to
      trends in IMR and NMR. RESULTS: IMR and NMR decreased between 1983 and 2005 for
      all birth weight and gestational age subgroups. There was an increase in births
      of very low birth weight infants from 1.2% to 1.5% (P < .001) over this period.
      The proportion of very low birth weight-infant deaths increased from 42.9% to
      54.8%, resulting in recent nonsignificant declines in IMR and NMR. The proportion
      of live-birth infants <500 g increased from 0.12% to 0.18% (P < .001). The
      adjusted IMR and NMR over time (excluding infants <500 g) have steeper declining
      trends than the ones including infants <500 g. The changes in overall IMR and NMR
      in recent years (2000-2005) are not statistically significant. However, the
      adjusted IMR and NMR trends during this time are highly significant. CONCLUSIONS:
      The increased proportions of infants <500 g and other low birth weight infants
      contribute greatly to the lack of a decrease in IMR and NMR from 2000 to 2005,
      although birth weight- and gestational age-specific IMR and NMR continue to
      decrease.

PMID- 23545382
TI  - Evaluation of an office protocol to increase exclusivity of breastfeeding.
AB  - OBJECTIVE: The purpose of this study was to determine whether implementing a
      program based on a clinical protocol affects breastfeeding rates within a
      pediatric primary care setting. Increasing breastfeeding rates is an important
      public health initiative identified by multiple agencies. METHODS: The Academy of
      Breastfeeding Medicine (ABM) clinical protocol ("The Breastfeeding-Friendly
      Physician's Office, Part 1: Optimizing Care for Infants and Children") was used
      as a template for the provision of breastfeeding services within a pediatric
      primary care clinic. There were 757 mother-infant pairs included in the study. A
      retrospective before-and-after study design was used. Data collection points
      included the hospital stay, the newborn visit, and the 2-, 4-, and 6-month health
      maintenance visits. The 2 groups were compared to estimate the protocol's
      effectiveness as a method of increasing breastfeeding rates. RESULTS: The results
      of this evaluation were positive for exclusive breastfeeding, with group
      comparisons showing a statistically significant increase in exclusive
      breastfeeding rates at all 5 time points. CONCLUSIONS: Our diverse patient
      population within a pediatric practice had increased initiation rates and
      exclusive breastfeeding rates after implementation of the ABM's breastfeeding
      friendly protocol. Families who receive care in a pediatric primary care setting
      that has implemented the ABM clinical protocol may have increased rates of
      exclusive breastfeeding.

PMID- 23545383
TI  - Salinomycin inhibits Akt/NF-kappaB and induces apoptosis in cisplatin resistant
      ovarian cancer cells.
AB  - BACKGROUND: Despite advances in treatment, ovarian cancer is the most lethal
      gynecologic malignancy. Therefore significant efforts are being made to develop
      novel strategies for the treatment of ovarian cancer. Salinomycin has been shown
      to be highly effective in the elimination of cancer stem cells both in vitro and
      in vivo. The present study focused on investigating important cell signaling
      molecules such as Akt and NF-kappaB during salinomycin-induced apoptosis in
      cisplatin resistant ovarian cancer cells (A2780cis). METHODS: MTT assay was
      performed to determine cell viability. Flow cytometry and DNA fragmentation assay
      were performed to analyze the effect on cell cycle and apoptosis. The expression
      of apoptosis related proteins was evaluated by Western blot analysis. RESULTS:
      The cell viability was significantly reduced by salinomycin treatment in a dose
      dependent manner. The flow cytometry result showed an increase in sub-G1 phase.
      Salinomycin inhibited the nuclear transportation of NF-kappaB, and downregulated
      Akt expression. Declined Bcl-2, activation of caspase-3 and increased PARP
      cleavage triggered apoptosis. Moreover, DNA fragmentation assay also revealed
      apoptotic induction. CONCLUSION: The result suggested that salinomycin-induced
      apoptosis in A2780cis was associated with inhibition of Akt/NF-kappaB. It may
      become a potential chemotherapeutic agent for the cisplatin resistant ovarian
      cancer therapy.

PMID- 23545384
TI  - Plasma exchange as a complementary approach to snake bite treatment: an academic
      emergency department's experiences.
AB  - Snake bites are leading causes of morbidity and mortality worldwide, especially
      in rural areas. Therapeutic plasma exchange has been used in the treatment of
      many different conditions such as immunologic diseases, toxicologic disorders,
      and snake envenomation. The aim of this study is to evaluate the efficacy of
      plasma exchange treatment on clinical status, outcomes, and discharge of patients
      who were bitten by venomous snakes. The study was conducted retrospectively in
      the Emergency Department of Gaziantep University from January 2002 to December
      2011. Thirty-seven patients were included in the present study. Routine
      biochemical and hematologic laboratory parameters were studied before and after
      plasma exchange. Demographic data, clinical status, and outcomes of patients were
      recorded. Plasma exchange was performed by using centrifugation technology via an
      intravenous antecubital or subclavian vein catheter access. Human albumin/fresh
      frozen plasma was used as replacement fluids. A significant correlation was seen
      between therapeutic plasma exchange and improvement of laboratory results. None
      of the study patients lost their limbs. Eight patients were sent to the intensive
      care unit. The mean length of the hospital stay was 12.2 days (4-28). All
      patients were discharged with good recovery. No complications were seen during
      the 3 months following discharge. Plasma exchange appears to be an effective
      treatment intervention for snake bite envenomations, especially in the management
      of hematologic problems and in limb preservation/salvage strategies. In addition
      to traditional treatment methods, plasma exchange should be considered by
      emergency physicians in cases of snake bite envenomation as a therapeutic
      approach to facilitate rapid improvement.

PMID- 23545385
TI  - Interaction between language and vision: it's momentary, abstract, and it
      develops.
AB  - In this paper, we present a case study that explores the nature and development
      of the mechanisms by which language interacts with and influences our ability to
      represent and retain information from one of our most important non-linguistic
      systems - vision. In previous work (Dessalegn & Landau, 2008), we showed that 4
      year-olds remembered conjunctions of visual features better when the visual
      target was accompanied by a sentence containing an asymmetric spatial predicate
      (e.g., the yellow is to the left of the black) but not when the visual target was
      accompanied by a sentence containing a novel noun (e.g., look at the dax) or a
      symmetric spatial predicate (e.g., the yellow is touching the black). In this
      paper, we extend these findings. In three experiments, 3, 4 and 6 year-olds were
      shown square blocks split in half by color vertically, horizontally or diagonally
      (e.g., yellow-left, black-right) and were asked to perform a delayed-matching
      task. We found that sentences containing spatial asymmetric predicates (e.g., the
      yellow is to the left of the black) and non-spatial asymmetric predicates (e.g.,
      the yellow is prettier than the black) helped 4 year-olds, although not to the
      same extent. By contrast, 3 year-olds did not benefit from different linguistic
      instructions at all while 6 year-olds performed at ceiling in the task with or
      without the relevant sentences. Our findings suggest by age 4, the effects of
      language on non-linguistic tasks depend on highly abstract representations of the
      linguistic instructions and are momentary, seen only in the context of the task.
      We further speculate that language becomes more automatically engaged in
      nonlinguistic tasks over development.

PMID- 23545386
TI  - The case of the missing pronouns: does mentally simulated perspective play a
      functional role in the comprehension of person?
AB  - Language comprehenders can mentally simulate perceptual and motor features of
      scenes they hear or read about (Barsalou, 1999; Glenberg & Kaschak, 2002; Zwaan,
      Stanfield, & Yaxley, 2002). Recent research shows that these simulations adopt a
      particular perspective (Borghi, Glenberg, & Kaschak, 2004; Brunye, Ditman,
      Mahoney, Augustyn, & Taylor, 2009). Moreover, features of utterances influence
      the perspective that comprehenders are led to adopt. For instance, language about
      you primes a participant visual perspective, while third person he and she prime
      an observer perspective. But what role does perspectival mental simulation play
      in the comprehension of person? On the one hand, the different perspectives
      adopted during language understanding could be necessary for successfully
      determining the meaning of an utterance. However, current empirical evidence is
      also compatible with the possibility that adopting a perspective in mental
      simulation is not essential to comprehending who did what to whom. If the latter
      is the case, then we should be able to find cases where language comprehenders
      understand who did what to whom without measurably performing mental simulation
      from a particular perspective. A candidate language that might display such a
      case is Japanese, where grammatical subject pronouns can be omitted when the
      subject is inferable from context. We replicated a previously used method for
      assessing perspectival mental simulation during language comprehension, but
      tailored it to Japanese. The results showed that when pronouns were present, like
      in English, sentences facilitated identification of an image matching the
      proposed perspective associated with the mentioned pronoun. This replicated the
      previous finding for English. But when the subject pronoun was omitted, so that
      the sentence did not explicitly mention the subject, there was no such effect.
      Nonetheless, native comprehenders of Japanese automatically and easily tracked
      who the subjects of the sentences with omitted subjects were. Together, these
      findings suggest that while grammatical person modulates visual perspective in
      mental simulation, visual perspective is not necessary for successful
      identification and representation of event participants.

PMID- 23545387
TI  - Memory constraints on infants' cross-situational statistical learning.
AB  - Infants are able to map linguistic labels to referents in the world by tracking
      co-occurrence probabilities across learning events, a behavior often termed cross
      situational statistical learning. This study builds upon existing research by
      examining infants' developing ability to aggregate and retrieve word-referent
      pairings over time. 16- and 20-month-old infants (N=32) were presented with a
      cross-situational statistical learning task in which half of the object-label
      pairings were presented in immediate succession (massed) and half were
      distributed across time (interleaved). Results revealed striking developmental
      differences in word mapping performance; infants in both age groups were able to
      learn pairings presented in immediate succession, but only 20-month-old infants
      were able to correctly infer pairings distributed over time. This work reveals
      significant constraints on infants' ability to aggregate and retrieve object
      label pairings across time and challenges theories of cross-situational
      statistical learning that rest on retrieval processes as successful and
      automatic.

PMID- 23545388
TI  - Phonological development in relation to native language and literacy: variations
      on a theme in six alphabetic orthographies.
AB  - Phonological development was assessed in six alphabetic orthographies (English,
      French, Greek, Icelandic, Portuguese and Spanish) at the beginning and end of the
      first year of reading instruction. The aim was to explore contrasting theoretical
      views regarding: the question of the availability of phonology at the outset of
      learning to read (Study 1); the influence of orthographic depth on the pace of
      phonological development during the transition to literacy (Study 2); and the
      impact of literacy instruction (Study 3). Results from 242 children did not
      reveal a consistent sequence of development as performance varied according to
      task demands and language. Phonics instruction appeared more influential than
      orthographic depth in the emergence of an early meta-phonological capacity to
      manipulate phonemes, and preliminary indications were that cross-linguistic
      variation was associated with speech rhythm more than factors such as syllable
      complexity. The implications of the outcome for current models of phonological
      development are discussed.

PMID- 23545389
TI  - Substantive learning bias or an effect of familiarity? Comment on Culbertson,
      Smolensky, and Legendre (2012).
AB  - Typologists have long observed that there are certain distributional patterns
      that are not evenly distributed among the world's languages. This discussion note
      revisits a recent experimental investigation of one such intriguing case, so
      called "universal 18", by Culbertson, Smolensky, and Legendre (2012). The authors
      find that adult learners are less likely to generalize an artificial grammar that
      involves the word order combination Adjective-before-Noun and Noun-before
      Numeral, and they attribute this to two factors: (1) a domain-general preference
      for consistency-i.e., a preference for either N before Adj/Num, or N after, and
      (2) a domain-specific unlearned universal bias against Adj-N+N-Num order. An
      alternative explanation for the second factor is that it involves a transfer
      effect from either Spanish-type languages or from English. The case for possible
      transfer from English is based on the fact that adjectives regularly occur after
      the nouns they modify in several English constructions, whereas numerals only
      quantify the nouns they follow in one construction that occurs extremely
      infrequently.

PMID- 23545395
TI  - Neurophysiological bases underlying the organization of intentional actions and
      the understanding of others' intention.
AB  - Philosophical and neuroscientific investigation on intentional actions focused on
      several different aspects, making difficult to define what should be meant with
      the concept of intention. Most of our everyday actions are constituted by complex
      and finely organized motor sequences, planned and executed in order to attain a
      desired final goal. In this paper, we will identify the final goal of the action
      as the motor intention of the acting individual. First, we will review the
      relative contribution of the vast neuroscientific literature on the role of
      different cortical areas in the organization of goal-directed movement. In
      particular, we will describe recent data on the cortical organization of natural
      action sequences, showing that this organization could be at the basis not only
      of our capacity of acting intentionally, but also of our ability to understand
      the motor intentions underlying others' behaviour which is crucial during social
      interactions. 

PMID- 23545396
TI  - Embryonic exposure to PFOS induces immunosuppression in the fish larvae of marine
      medaka.
AB  - Perfluorooctane sulfonate (PFOS) is a global pollutant that has been studied
      because of its health risks. PFOS has been shown to have immune toxicity.
      However, few studies have focused on the immune responses of fish larvae exposed
      to PFOS at early embryonic stages. In this study, the larvae of marine medaka
      (Oryzias melastigma) were evaluated for postnatal immune toxicity after embryonic
      exposure to PFOS (0, 1, 4 and 16mg/L) from 2 days post fertilization (dpf). The
      physiological indices, survival rates, PFOS elimination kinetics, liver histology
      and gene transcription in the fish larvae were examined after depuration. The
      elimination rate constant (ke) of PFOS in the fish larvae ranged from 0.04+/-0.00
      to 0.07+/-0.01d(-1). Embryonic exposure to PFOS severely compromised the
      postnatal survival of fish larvae after depuration. The survival rate and body
      width decreased in a concentration dependent manner. PFOS impaired the liver
      structure in the fish larvae by enlarging the cell nuclei and damaging the cell
      structure. To explore the toxic mechanisms that affect the immune responses, fish
      larvae at 27 days post hatch (dph) were exposed to lipopolysaccharides (LPS) to
      elicit an inflammatory response. The inflammatory response and immune-related
      genes were generally up-regulated in the fish larvae following embryonic exposure
      to 0mg/L PFOS. In contrast, the genes were all markedly down-regulated in the
      fish larvae following embryonic exposure to 1 and 4mg/L PFOS. These results
      suggest that early life exposure to PFOS could alter immunoregulation functions,
      leading to functional dysfunction or weakness of the immune system in fish
      larvae. The immunosuppression effects caused by PFOS could reduce the efficiency
      of immune defense mechanisms and increase the susceptibility to infectious
      agents, which may contribute to various detrimental health effects in the fish
      larvae.

PMID- 23545397
TI  - Formulation of carbenoxolone for delivery to the skin.
AB  - Carbenoxolone (CEX), a semi-synthetic derivative of glycyrrhetinic acid, has
      previously been used as a disodium salt for the management of dyspepsia and
      peptic ulcer because of its anti-inflammatory properties. Although glycyrrhetinic
      acid is available in pharmaceutical and personal care products for skin care, the
      topical use of the free acid form of CEX, has not previously been reported. In
      this work we investigated the percutaneous penetration of CEX. Solubility and
      permeability studies were conducted using a range of solvents or skin permeation
      enhancers (SPEs) commonly used for skin delivery. Binary combinations of dimethyl
      isosorbide (DMI) and TranscutolTM (TC) with isopropyl myristate (IPM) were
      effective in promoting skin permeation of CEX although individual solvents were
      not. Alternative fatty acid esters to IPM were subsequently investigated with the
      most promising formulation consisting of TC and propylene glycol laurate (PGL).
      Interestingly, propylene glycol monolaurate (PGML) did not demonstrate comparable
      efficacy when combined with TC. A ternary formulation consisting of TC, PGL and
      IPM demonstrated the best permeation enhancement of CEX compared with all other
      vehicles. The findings confirm (i) the feasibility of promoting CEX penetration
      across the skin (ii) the synergistic effect of combinations of solvents and SPEs
      on dermal and transdermal delivery (iii) the necessity for more fundamental
      studies to explain the differential effects of fatty acid esters on the skin
      barrier.

PMID- 23545398
TI  - Thermodynamic study of binary system Propafenone Hydrocloride with Metoprolol
      Tartrate: solid-liquid equilibrium and compatibility with alpha-lactose
      monohydrate and corn starch.
AB  - Solid-liquid equilibrium (SLE) for binary mixture of Propafenone Hydrocloride
      (PP) with Metoprolol Tartrate (MT) was investigated using differential scanning
      calorimetry (DSC) and corresponding activity coefficients were calculated. Simple
      eutectic behavior for this system was observed. The excess thermodynamic
      functions: G(E) and S(E) for the pre-, post-, and eutectic composition have been
      obtained using the computed activity coefficients data of the eutectic phase with
      their excess chemical potentials MUi(E) (i=1, 2). The experimental solid-liquid
      phase temperatures were compared with predictions obtained from available
      eutectic equilibrium models. The results indicate non-ideality in this mixture.
      Also, the compatibility of each component and their eutectic mixture with usual
      excipients was investigated, and the DSC experiments indicate possible weak
      interactions with alpha-lactose monohydrate and compatibility with corn starch.
      The results obtained were confirmed by FT-IR measurements.

PMID- 23545400
TI  - Do events have effects? A commentary on Polizzi and Draper.
AB  - Polizzi and Draper offer an elegant application of a phenomenological approach to
      the practice of psychotherapy within the forensic context. They describe how-even
      though these contexts are constituted through layers of sedimented meanings that
      pre-signify setting and participants-therapists and inmates may find ways to be
      open to each other and to genuine encounters that they conceptualize as "events."
      In this commentary, I raise a question that the authors did not appear to
      consider, which is that of whether these "events" have "effects" either for the
      participants themselves or for the broader context as well. I contrast a
      hermeneutic-Heideggerian approach, which does not necessarily concern itself with
      such effects-as they are considered irrelevant to the genuineness of the
      interpersonal encounter-and a transcendental Husserlian-Deleuzian approach, in
      which such events are thought to have profound effects for all parties involved,
      including the broader context.

PMID- 23545399
TI  - Epidemiological and phylogenetic analysis of institutional mouse parvoviruses.
AB  - Mouse parvoviruses (MPVs) are small, single-stranded, 5 kb DNA viruses that are
      subclinical and endemic in many laboratory mouse colonies. MPVs cause more
      distinctive deleterious effects in immune-compromised or genetically-engineered
      mice than immuno-competent mice. At the University of Louisville (U of L), there
      was an unexpected increase of MPV sero-positivity for MPV infections in mouse
      colonies between January 2006 and February 2007, resulting in strategic husbandry
      changes aimed at controlling MPV spread throughout the animal facility. To
      investigate these MPVs, VP2 genes of seven MPVs were cloned and sequenced from
      eight documented incidences by PCR technology. The mutations in these VP2 genes
      were compared to those found at the Genbank database (NCBI;
      http://www.ncbi.nlm.nih.gov) and an intra-institutional phylogenetic tree for MPV
      infections at U of L was constructed. We discovered that the seven MPV isolates
      were different from those in Genbank and were not identical to each other. These
      MPVs were designated MPV-UL1 to 7; none of them were minute virus of mice (MVMs).
      Four isolates could be classified as MPV1, one was classified as MPV2, and two
      were defined as novel types with less than 96% and 94% homology with existing MPV
      types. Considering that all seven isolates had mutations in their VP2 genes and
      no mutations were observed in VP2 genes of MPV during a four-month time period of
      incubation, we concluded that all seven MPVs isolated at U of L between 2006 and
      2007 probably originated from different sources. Serological survey for MPV
      infections verified that each MPV outbreak was controlled without further
      contamination within the institution.

PMID- 23545402
TI  - Modelling nitrogen retention in floodplains with different degrees of degradation
      for three large rivers in Germany.
AB  - Floodplains perform a variety of ecosystem functions and services - more than
      many other ecosystems. One of these ecosystem services is the reduction in
      nitrogen (N) loads and a subsequent improvement to the water quality. Since
      diffuse and also point nitrogen sources continue to cause a variety of problems
      in rivers and floodplains, inundated floodplains could act as net sinks for N and
      are therefore of great importance throughout Germany and Europe. This study
      analyses the effects of riparian floodplains on N-retention on the landscape
      scale for three large river systems with different degrees of degradation. Two
      approaches, differing in terms of the complexity of their respective input data
      and methods, were applied under wet and dry conditions. Whereas the proxy-based
      approach considers proxy values for N-retention, the model-based approach
      accounts for event-driven dynamic input data such as the extent of the inundated
      floodplain and incoming loads. Comparing the results of the two approaches it can
      be observed that floodplains of the near-natural river can retain up to 4% of the
      river load under wet conditions. During such conditions N-retention in
      floodplains is similar to that of rivers. For the two other floodplains, the
      results of the two approaches were quite different, showing lower N-retention
      capacities. However, for these floodplains as well, both approaches are suitable
      for calculating measurable N-retention rates, which is an important result
      because it also suggests that even degraded floodplains still preserve this
      particular ecosystem function and therefore still contribute to improving the
      quality of river water.

PMID- 23545403
TI  - Nitric oxide (NO) in alleviation of heavy metal induced phytotoxicity and its
      role in protein nitration.
AB  - Nitric oxide (NO) is recognized as a biological messenger in various tissues to
      regulate diverse range of physiological process including growth, development and
      response to abiotic and biotic factors. The NO emission from plants is known
      since the 1970s, and there is copious information on the multiple effects of
      exogenously applied NO on different physiological and biochemical processes of
      plants. Heavy metal toxicity is one of the major abiotic stresses leading to
      hazardous effects in plants and its toxicity is based on chemical and physical
      property. A common consequence of heavy metal toxicity is the uncontrolled and
      excessive accumulation of reactive oxygen species (ROS) which leads to
      peroxidation of lipids, oxidation of protein, inactivation of enzymes, DNA damage
      and/or interact with other vital constituents of plant cells. Recently, an
      increasing number of articles have reported the effects of exogenous NO on
      alleviating heavy metal toxicity in plants but knowledge of physiological
      mechanisms of NO in alleviating heavy metal toxicity is quite limited, and some
      results contradict one another. Therefore, to help clarify the roles of NO in
      heavy metal tolerance, it is important to review and discuss the recent advances
      on this area of research. NO can provoke both beneficial and harmful effects,
      which depend on the concentration and location of NO in the plant cells. NO
      alleviates the harmfulness of the ROS, and reacts with other target molecules,
      and regulates the expression of stress responsive genes under various stress
      conditions. This manuscript includes, the latest advances in understanding the
      effects of endogenous NO on heavy metal toxicity and the mechanisms and role of
      NO as an antioxidant as well as in protein nitration are highlighted.

PMID- 23545405
TI  - Nitric oxide synthase-dependent "on/off" switch and apoptosis in freshwater and
      aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac
      muscle.
AB  - African lungfishes (Protopterus spp.) are obligate air breathers which enter in a
      prolonged torpor (aestivation) in association with metabolic depression, and
      biochemical and morpho-functional readjustments during the dry season. During
      aestivation, the lungfish heart continues to pump, while the skeletal muscle
      stops to function but can immediately contract during arousal. Currently, nothing
      is known regarding the orchestration of the multilevel rearrangements occurring
      in myotomal and myocardial muscles during aestivation and arousal. Because of its
      universal role in cardio-circulatory and muscle homeostasis, nitric oxide (NO)
      could be involved in coordinating these stress-induced adaptations. Western
      blotting and immunofluorescence microscopy on cardiac and skeletal muscles of
      Protopterus annectens (freshwater, 6months of aestivation and 6days after
      arousal) showed that expression, localization and activity of the endothelial
      like nitric oxide synthase (eNOS) isoform and its partners Akt and Hsp-90 are
      tissue-specifically modulated. During aestivation, phospho-eNOS/eNOS and phospho
      Akt/Akt ratios increased in the heart but decreased in the skeletal muscle. By
      contrast, Hsp-90 increased in both muscle types during aestivation. TUNEL assay
      revealed that increased apoptosis occurred in the skeletal muscle of aestivating
      lungfish, but the myocardial apoptotic rate of the aestivating lungfish remained
      unchanged as compared with the freshwater control. Consistent with the preserved
      cardiac activity during aestivation, the expression of apoptosis repressor (ARC)
      also remained unchanged in the heart of aestivating and aroused fish as compared
      with the freshwater control. Contrarily, ARC expression was strongly reduced in
      the skeletal muscle of aestivating lungfish. On the whole, our data indicate that
      changes in the eNOS/NO system and cell turnover are implicated in the morpho
      functional readjustments occurring in lungfish cardiac and skeletal muscle during
      the switch from freshwater to aestivation, and between the maintenance and
      arousal phases of aestivation.

PMID- 23545406
TI  - Pioglitazone protects against renal ischemia-reperfusion injury by enhancing
      antioxidant capacity.
AB  - BACKGROUND: In our previous study, we showed that pioglitazone exerts protective
      effects on renal ischemia-reperfusion injury (IRI) in mice by abrogating renal
      cell apoptosis. Oxidative stress due to excessive production of reactive oxygen
      species and subsequent lipid peroxidation plays a critical role in renal IRI. The
      purpose of the current study is to demonstrate the effect of pioglitazone on
      renal IRI by modulation of oxidative stress. MATERIALS AND METHODS: IRI was
      induced by bilateral renal ischemia for 45 min followed by reperfusion. Thirty
      healthy male Balb/c mice were randomly assigned to one of the following groups:
      phosphate buffer solution (PBS) + IRI, pioglitazone + IRI, PBS + sham IRI,
      pioglitazone + sham IRI. Kidney function tests and kidney antioxidant activities
      were determined 24 h after reperfusion. RESULTS: Pretreatment with pioglitazone
      produced reduction in serum levels of blood urea nitrogen and creatinine caused
      by IRI. Pretreatment with pioglitazone before IRI resulted in a higher level of
      kidney enzymatic activities of superoxide dismutase, glutathione, catalase, and
      total antioxidant capacity than in the PBS-pretreated IRI group. CONCLUSIONS: Our
      results indicate that pioglitazone can provide protection for kidneys against IRI
      by enhancing antioxidant capacity. Therefore, pioglitazone could be a potential
      therapeutic approach to prevent renal IRI relevant to various clinical
      conditions.

PMID- 23545404
TI  - Nitroxyl accelerates the oxidation of oxyhemoglobin by nitrite.
AB  - Angeli's salt (Na2N2O3) decomposes into nitroxyl (HNO) and nitrite (NO2(-)),
      compounds of physiological and therapeutic interest for their impact on
      biological signaling both through nitric oxide and nitric oxide independent
      pathways. Both nitrite and HNO oxidize oxygenated hemoglobin to methemoglobin.
      Earlier work has shown that HNO catalyzes the reduction of nitrite by
      deoxygenated hemoglobin. In this work, we have shown that HNO accelerates the
      oxidation of oxygenated hemoglobin by NO2(-). We have demonstrated this HNO
      mediated acceleration of the nitrite/oxygenated hemoglobin reaction with
      oxygenated hemoglobin being in excess to HNO and nitrite (as would be found under
      physiological conditions) by monitoring the formation of methemoglobin in the
      presence of Angeli's salt with and without added NO2(-). In addition, this
      acceleration has been demonstrated using the HNO donor 4-nitrosotetrahydro-2H
      pyran-4-yl pivalate, a water-soluble acyloxy nitroso compound that does not
      release NO2(-) but generates HNO in the presence of esterase. This HNO donor was
      used both with and without NO2(-) and acceleration of the NO2(-) induced
      formation of methemoglobin was observed. We found that the acceleration was not
      substantially affected by catalase, superoxide dismutase, c-PTIO, or IHP,
      suggesting that it is not due to formation of extramolecular peroxide, NO2 or
      H2O2, or to modulation of allosteric properties. In addition, we found that the
      acceleration is not likely to be related to HNO binding to free reduced
      hemoglobin, as we found HNO binding to reduced hemoglobin to be much weaker than
      has previously been proposed. We suggest that the mechanism of the acceleration
      involves local propagation of autocatalysis in the nitrite-oxygenated Hb
      reaction. This acceleration of the nitrite oxyhemoglobin reaction could affect
      studies aimed at understanding physiological roles of HNO and perhaps nitrite and
      use of these agents in therapeutics such as hemolytic anemias, heart failure, and
      ischemia reperfusion injury.

PMID- 23545407
TI  - Racial and ethnic disparities in the treatment of unruptured thoracoabdominal
      aortic aneurysms in the United States.
AB  - PURPOSE: Previous studies have found increased mortality in minority patients
      undergoing abdominal aortic aneurysm repair. The goal of this study was to
      identify racial and ethnic disparities in patients undergoing thoracoabdominal
      aortic aneurysm repair. MATERIALS AND METHODS: We queried the Nationwide
      Inpatient Sample (2005-2009) using International Classification of Diseases,
      Ninth Revision, Clinical Modification codes for repair of unruptured
      thoracoabdominal aneurysms. The primary outcome was death. Secondary outcomes
      included postoperative complications. We performed multivariate analysis
      adjusting for age, gender, race, comorbidities (Charlson index), insurance type,
      and surgeon and hospital operative volumes and characteristics. RESULTS: Overall,
      1541 white, 207 black, and 117 Hispanic patients underwent thoracoabdominal
      aortic aneurysm repair. White patients tended to be older (P = 0.003), whereas
      black patients had a higher incidence of diabetes mellitus (P = 0.04). Black and
      Hispanic patients were less likely to have an elective admission (P < 0.001) and
      more likely to have repair performed at a hospital with a lower average annual
      surgical volume (P = 0.04). Postoperative complications were similar among the
      groups (P = 0.31). On multivariate analysis, increased mortality was
      independently associated with Hispanic ethnicity (relative ratio [RR], 2.57; 95%
      confidence interval [CI], 1.25-5.25; P = 0.01), cerebrovascular disease (RR,
      1.88; 95% CI, 1.10-3.23; P = 0.02), and age (RR, 1.04; 95% CI, 1.01-1.07; P =
      0.004). CONCLUSIONS: Hispanic ethnicity is independently associated with
      increased mortality after repair of unruptured thoracoabdominal aneurysms. This
      finding was independent of preoperative comorbidities, postoperative
      complications, and surgeon and hospital operative volumes. Further studies are
      necessary to determine whether this mortality difference persists after the index
      hospitalization.

PMID- 23545408
TI  - Laparoscopic surgery for orthotopic kidney transplant in the pig model.
AB  - BACKGROUND: Laparoscopic surgery has become the preferred approach in surgical
      practice due to multiple benefits. Over the last decade, kidney transplant by
      laparoscopic or robotic techniques have been explored. The aim of this study is
      to establish a new laparoscopic technique for kidney orthotopic transplant.
      MATERIALS AND METHODS: The study was approved by the Animal Ethics Committee of
      the University. Ten live female pigs (Sus scrofa), weighing 45-50 kg, underwent
      laparoscopic kidney orthotopic transplant on left side under general anesthesia,
      and the opposite right kidney was defunctioned by complete ligation of the ureter
      at the same time. RESULTS: The vital signs of all pigs were stable during the
      surgery and postoperative period. There were no intraoperative complications and
      no conversion to open surgery. The laparoscopic kidney transplant was successful
      in seven of 10 pigs. Seven pigs were observed up to 4 wk as planned in the study.
      DISCUSSION: To our knowledge, this is the first study of laparoscopic kidney
      orthotopic transplant in pig model with satisfactory immediate graft function. It
      was demonstrated that laparoscopic kidney transplant is a feasible, reliable, and
      safe procedure. However, it is a very demanding technique. Adequate training is
      mandatory for performing laparoscopic kidney transplant. This study could be used
      as a training model for surgeons who wish to perform human laparoscopic kidney
      transplant in the future.

PMID- 23545409
TI  - Optimal pressure of abdominal gas insufflation for bleeding control in a severe
      swine splenic injury model.
AB  - BACKGROUND: We previously demonstrated that abdominal gas insufflation (AGI)
      reduces intra-abdominal bleeding. To date, this is the only method that holds
      promise for reducing mortality from internal bleeding in a pre-hospital setting.
      We aimed to assess the optimal AGI pressure and the effectiveness of a portable
      miniaturized insufflator in abdominal bleeding control. MATERIALS AND METHODS: We
      randomized 15 Yorkshire swine to receive AGI of 20, 25 or 30 mm Hg after
      sustaining a standardized severe splenic injury, to determine the ideal pressure
      for optimal bleeding control. We randomized six (40%) to insufflation with a
      custom-designed, battery-operated, 7-oz portable CO2 tank, whereas we used a
      standard laparoscopic insufflator for the remainder. Intravenous fluid boluses
      were administered as needed to maintain a mean arterial pressure of >60 mm Hg. At
      30 min, the animals were re-laparotomized and their hemoperitoneum was
      quantified. RESULTS: Target peritoneal pressures were achieved and maintained
      successfully with both insufflation methods. There was a trend toward greater
      blood loss and fluid requirements in the 30-mmHg group (P = 0.71 and 0.97,
      respectively). Increasing the AGI led to less predictable blood loss and fluid
      resuscitation requirements, as well as worsening of tissue perfusion markers (pH
      and lactate), likely because of iatrogenic abdominal compartment syndrome.
      CONCLUSIONS: All target peritoneal pressures were easily and reliably achieved
      with the portable CO2 insufflator. Abdominal gas insufflation produced optimal
      bleeding control at 20 mm Hg. This technology could be used in a pre-hospital
      setting to control otherwise lethal hemorrhage at pressures typically used for
      standard laparoscopic surgery and proven to be safe.

PMID- 23545410
TI  - Rac1 signaling regulates sepsis-induced pathologic inflammation in the lung via
      attenuation of Mac-1 expression and CXC chemokine formation.
AB  - Excessive neutrophil recruitment is a major feature in septic lung damage
      although the signaling mechanisms behind pulmonary infiltration of neutrophils in
      sepsis remain elusive. In the present study, we hypothesized that Rac1 might play
      an important role in pulmonary neutrophil accumulation and tissue injury in
      abdominal sepsis. Male C57BL/6 mice were treated with Rac1 inhibitor NSC23766 (5
      mg/kg) before cecal ligation and puncture (CLP). Bronchoalveolar lavage fluid and
      lung tissue were collected for the quantification of neutrophil recruitment and
      edema and CXC chemokine formation. Blood was collected for the determination of
      Mac-1 on neutrophils and proinflammatory compounds in plasma. Gene expression of
      CXC chemokines and tumor necrosis factor alpha was determined by quantitative
      reverse transcription-polymerase chain reaction in alveolar macrophages. Rac1
      activity was increased in lungs from septic animals, and NSC23766 significantly
      decreased pulmonary activity of Rac1 induced by CLP. Administration of NSC23766
      markedly reduced CLP-triggered neutrophil infiltration, edema formation, and
      tissue damage in the lung. Inhibition of Rac1 decreased CLP-induced neutrophil
      expression of Mac-1 and pulmonary formation of CXC chemokines. Moreover, NSC23766
      abolished the sepsis-evoked elevation of messenger RNA levels of CXC chemokines
      and tumor necrosis factor alpha in alveolar macrophages. Rac1 inhibition
      decreased the CLP-induced increase in plasma levels of high mobility group
      protein B1 and interleukin 6, indicating a role of Rac1 in systemic inflammation.
      In conclusion, our results demonstrate that Rac1 signaling plays a key role in
      regulating pulmonary infiltration of neutrophils and tissue injury via regulation
      of chemokine production in the lung and Mac-1 expression on neutrophils in
      abdominal sepsis. Thus, targeting Rac1 activity might be a useful strategy to
      protect the lung in abdominal sepsis. 

PMID- 23545411
TI  - Mammalian HECT ubiquitin-protein ligases: biological and pathophysiological
      aspects.
AB  - Members of the HECT family of E3 ubiquitin-protein ligases are characterized by a
      C-terminal HECT domain that catalyzes the covalent attachment of ubiquitin to
      substrate proteins and by N-terminal extensions of variable length and domain
      architecture that determine the substrate spectrum of a respective HECT E3. Since
      their discovery in 1995, it has become clear that deregulation of distinct HECT
      E3s plays an eminent role in human disease or disease-related processes including
      cancer, cardiovascular and neurological disorders, viral infections, and immune
      response. Thus, a detailed understanding of the structure-function aspects of
      HECT E3s as well as the identification and characterization of the substrates and
      regulators of HECT E3s is critical in developing new approaches in the treatment
      of respective diseases. In this review, we summarize what is currently known
      about mammalian HECT E3s, with a focus on their biological functions and roles in
      pathophysiology.This article is part of a Special Issue entitled: Ubiquitin
      Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. 

PMID- 23545412
TI  - Proteasome dynamics.
AB  - Proteasomes are highly conserved multisubunit protease complexes and occur in the
      cyto- and nucleoplasm of eukaryotic cells. In dividing cells proteasomes exist as
      holoenzymes and primarily localize in the nucleus. During quiescence they
      dissociate into proteolytic core and regulatory complexes and are sequestered
      into motile cytosolic clusters. Proteasome clusters rapidly clear upon the exit
      from quiescence, where proteasome core and regulatory complexes reassemble and
      localize to the nucleus again. The mechanisms underlying proteasome transport and
      assembly are not yet understood. Here, I summarize our present knowledge about
      nuclear transport and assembly of proteasomes in yeast and project our studies in
      this eukaryotic model organism to the mammalian cell system. This article is part
      of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas
      Sommer and Dieter H. Wolf. 

PMID- 23545413
TI  - The type II cGMP dependent protein kinase regulates GluA1 levels at the plasma
      membrane of developing cerebellar granule cells.
AB  - Trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
      (AMPARs) is regulated by specific interactions with other proteins and by post
      translational mechanisms, such as phosphorylation. We have found that the type II
      cGMP-dependent protein kinase (cGKII) phosphorylates GluA1 (formerly GluR1) at
      S845, augmenting the surface expression of AMPARs at both synaptic and
      extrasynaptic sites. Activation of cGKII by 8-Br-cGMP enhances the surface
      expression of GluA1, whereas its inhibition or suppression effectively diminished
      the expression of this protein at the cell surface. In granule cells, NMDA
      receptor activation (NMDAR) stimulates nitric oxide and cGMP production, which in
      turn activates cGKII and induces the phosphorylation of GluA1, promoting its
      accumulation in the plasma membrane. GluA1 is mainly incorporated into calcium
      permeable AMPARs as exposure to 8-Br-cGMP or NMDA activation enhanced AMPA
      elicited calcium responses that are sensitive to NASPM inhibition. We summarize
      evidence for an increase of calcium permeable AMPA receptors downstream of NMDA
      receptor activation that might be relevant for granule cell development and
      plasticity.

PMID- 23545414
TI  - Substrate recognition in selective autophagy and the ubiquitin-proteasome system.
AB  - Dynamic protein turnover through regulated protein synthesis and degradation
      ensures cellular growth, proliferation, differentiation and adaptation.
      Eukaryotic cells utilize two mechanistically distinct but largely complementary
      systems - the 26S proteasome and the lysosome (or vacuole in yeast and plants) -
      to effectively target a wide range of proteins for degradation. The concerted
      action of the ubiquitination machinery and the 26S proteasome ensures the
      targeted and tightly regulated degradation of a subset of commonly short-lived
      cellular proteins. Autophagy is a distinct degradation pathway, which transports
      a highly heterogeneous set of cargos in dedicated vesicles, called
      autophagosomes, to the lysosome. There the cargo becomes degraded and its
      molecular building blocks are recycled. While general autophagy randomly engulfs
      portions of the cytosol, selective autophagy employs dedicated cargo adaptors to
      specifically enrich the forming autophagosomes for a certain type of cargo as a
      response to various intra- or extracellular signals. Selective autophagy targets
      a wide range of cargos including long-lived proteins and protein complexes,
      organelles, protein aggregates and even intracellular microbes. In this review we
      summarize available data on cargo recognition mechanisms operating in selective
      autophagy and the ubiquitin-proteasome system (UPS), and emphasize their
      differences and common themes. Moreover, we derive general regulatory principles
      underlying cargo recognition in selective autophagy, and describe the system-wide
      crosstalk between these two cellular protein degradation systems. This article is
      part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors:
      Thomas Sommer and Dieter H. Wolf. 

PMID- 23545415
TI  - PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.
AB  - PRIMA-1 is a chemical compound identified as a growth suppressor of tumor cells
      expressing mutant p53. We previously found that in the MDA-MB-231 cell line
      expressing high level of the mutant p53-R280K protein, PRIMA-1 induced p53
      ubiquitination and degradation associated to cell death. In this study, we
      investigated the ability of PRIMA-1 to induce autophagy in cancer cells. In MDA
      MB-231 and HCT116 cells, expressing mutant or wild type p53, respectively,
      autophagy occurred following exposure to PRIMA-1, as shown by acridine orange
      staining, anti-LC3 immunofluorescence and immunoblots, as well as by electron
      microscopy. Autophagy was triggered also in the derivative cell lines knocked
      down for p53, although to a different extent than in the parental cells
      expressing mutant or wild type p53. In particular, while wild type p53 limited
      PRIMA-1 induced autophagy, mutant p53 conversely promoted autophagy, thus
      sustaining cell viability following PRIMA-1 treatment. Therefore, the autophagic
      potential of PRIMA-1, besides being cell context dependent, could be modulated in
      a different way by the presence of wild type or mutant p53. Furthermore, since
      both cell lines lacking p53 were more sensitive to the cytotoxic effect of PRIMA
      1 than the parental ones, our findings suggest that a deregulated autophagy may
      favor cell death induced by this drug.

PMID- 23545417
TI  - Mechanisms of action of Bcl-2 family proteins.
AB  - The Bcl-2 family of proteins controls a critical step in commitment to apoptosis
      by regulating permeabilization of the mitochondrial outer membrane (MOM). The
      family is divided into three classes: multiregion proapoptotic proteins that
      directly permeabilize the MOM; BH3 proteins that directly or indirectly activate
      the pore-forming class members; and the antiapoptotic proteins that inhibit this
      process at several steps. Different experimental approaches have led to several
      models, each proposed to explain the interactions between Bcl-2 family proteins.
      The discovery that many of these interactions occur at or in membranes as well as
      in the cytoplasm, and are governed by the concentrations and relative binding
      affinities of the proteins, provides a new basis for rationalizing these models.
      Furthermore, these dynamic interactions cause conformational changes in the Bcl-2
      proteins that modulate their apoptotic function, providing additional potential
      modes of regulation.

PMID- 23545416
TI  - Caspase functions in cell death and disease.
AB  - Caspases are a family of endoproteases that provide critical links in cell
      regulatory networks controlling inflammation and cell death. The activation of
      these enzymes is tightly controlled by their production as inactive zymogens that
      gain catalytic activity following signaling events promoting their aggregation
      into dimers or macromolecular complexes. Activation of apoptotic caspases results
      in inactivation or activation of substrates, and the generation of a cascade of
      signaling events permitting the controlled demolition of cellular components.
      Activation of inflammatory caspases results in the production of active
      proinflammatory cytokines and the promotion of innate immune responses to various
      internal and external insults. Dysregulation of caspases underlies human diseases
      including cancer and inflammatory disorders, and major efforts to design better
      therapies for these diseases seek to understand how these enzymes work and how
      they can be controlled.

PMID- 23545418
TI  - Replication clamps and clamp loaders.
AB  - To achieve the high degree of processivity required for DNA replication, DNA
      polymerases associate with ring-shaped sliding clamps that encircle the template
      DNA and slide freely along it. The closed circular structure of sliding clamps
      necessitates an enzyme-catalyzed mechanism, which not only opens them for
      assembly and closes them around DNA, but specifically targets them to sites where
      DNA synthesis is initiated and orients them correctly for replication. Such a
      feat is performed by multisubunit complexes known as clamp loaders, which use ATP
      to open sliding clamp rings and place them around the 3' end of primer-template
      (PT) junctions. Here we discuss the structure and composition of sliding clamps
      and clamp loaders from the three domains of life as well as T4 bacteriophage, and
      provide our current understanding of the clamp-loading process.

PMID- 23545419
TI  - Clinical and molecular features of POLG-related mitochondrial disease.
AB  - The inability to replicate mitochondrial genomes (mtDNA) by the mitochondrial DNA
      polymerase (pol gamma) leads to a subset of mitochondrial diseases. Many
      mutations in POLG, the gene that encodes pol gamma, have been associated with
      mitochondrial diseases such as myocerebrohepatopathy spectrum (MCHS) disorders,
      Alpers-Huttenlocher syndrome, myoclonic epilepsy myopathy sensory ataxia (MEMSA),
      ataxia neuropathy spectrum (ANS), and progressive external ophthalmoplegia (PEO).
      This chapter explores five important topics in POLG-related disease: (1) clinical
      symptoms that identify and distinguish POLG-related diseases, (2) molecular
      characterization of defects in polymerase activity by POLG disease variants, (3)
      the importance of holoenzyme formation in disease presentation, (4) the role of
      pol gamma exonuclease activity and mutagenesis in disease and aging, and (5)
      novel approaches to therapy and avoidance of toxicity based on primary research
      in pol gamma replication.

PMID- 23545420
TI  - Base excision repair.
AB  - Base excision repair (BER) corrects DNA damage from oxidation, deamination and
      alkylation. Such base lesions cause little distortion to the DNA helix structure.
      BER is initiated by a DNA glycosylase that recognizes and removes the damaged
      base, leaving an abasic site that is further processed by short-patch repair or
      long-patch repair that largely uses different proteins to complete BER. At least
      11 distinct mammalian DNA glycosylases are known, each recognizing a few related
      lesions, frequently with some overlap in specificities. Impressively, the damaged
      bases are rapidly identified in a vast excess of normal bases, without a supply
      of energy. BER protects against cancer, aging, and neurodegeneration and takes
      place both in nuclei and mitochondria. More recently, an important role of uracil
      DNA glycosylase UNG2 in adaptive immunity was revealed. Furthermore, other DNA
      glycosylases may have important roles in epigenetics, thus expanding the
      repertoire of BER proteins.

PMID- 23545421
TI  - Postreplicative mismatch repair.
AB  - The mismatch repair (MMR) system detects non-Watson-Crick base pairs and strand
      misalignments arising during DNA replication and mediates their removal by
      catalyzing excision of the mispair-containing tract of nascent DNA and its error
      free resynthesis. In this way, MMR improves the fidelity of replication by
      several orders of magnitude. It also addresses mispairs and strand misalignments
      arising during recombination and prevents synapses between nonidentical DNA
      sequences. Unsurprisingly, MMR malfunction brings about genomic instability that
      leads to cancer in mammals. But MMR proteins have recently been implicated also
      in other processes of DNA metabolism, such as DNA damage signaling, antibody
      diversification, and repair of interstrand cross-links and oxidative DNA damage,
      in which their functions remain to be elucidated. This article reviews the
      progress in our understanding of the mechanism of replication error repair made
      during the past decade.

PMID- 23545422
TI  - Endoplasmic reticulum structure and interconnections with other organelles.
AB  - The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle
      comprised of functionally and structurally distinct domains including the nuclear
      envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane
      contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and
      peroxisomes. These domains are required for multiple cellular processes,
      including synthesis of proteins and lipids, calcium level regulation, and
      exchange of macromolecules with various organelles at ER-membrane contact sites.
      The ER maintains its unique overall structure regardless of dynamics or transfer
      at ER-organelle contacts. In this review, we describe the numerous factors that
      contribute to the structure of the ER.

PMID- 23545423
TI  - Sphingolipid homeostasis in the endoplasmic reticulum and beyond.
AB  - Sphingolipids are a diverse group of lipids that have essential cellular roles as
      structural components of membranes and as potent signaling molecules. In recent
      years, a detailed picture has emerged of the basic biochemistry of sphingolipids
      from their initial synthesis in the endoplasmic reticulum (ER), to their
      elaboration into complex glycosphingolipids, to their turnover and degradation.
      However, our understanding of how sphingolipid metabolism is regulated in
      response to metabolic demand and physiologic cues remains incomplete. Here I
      discuss new insights into the mechanisms that ensure sphingolipid homeostasis,
      with an emphasis on the ER as a critical regulatory site in sphingolipid
      metabolism. In particular, Orm family proteins have recently emerged as key ER
      localized mediators of sphingolipid homeostasis. A detailed understanding of how
      cells sense and control sphingolipid production promises to provide key insights
      into membrane function in health and disease.

PMID- 23545424
TI  - Small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration
      in an Alzheimer's mouse model.
AB  - The p75 neurotrophin receptor (p75(NTR)) is associated with multiple mechanisms
      linked to Alzheimer's disease (AD); hence, modulating its function might confer
      therapeutic effects. In previous in vitro work, we developed small molecule
      p75(NTR) ligands that inhibited amyloid-beta-induced degenerative signaling and
      prevented neurite degeneration. In the present study, a prototype p75(NTR)
      ligand, LM11A-31, was administered orally to the Thy-1 hAPP(Lond/Swe) (APP(L/S))
      AD mouse model. LM11A-31 reached brain concentrations known to inhibit
      degenerative signaling without toxicity or induction of hyperalgesia. It
      prevented deficits in novel object recognition after 2.5 months and, in a
      separate cohort, deficits in Y-maze performance after 3 months of treatment.
      Stereology studies found that the number and size of basal forebrain cholinergic
      neurons, which are normal in APP(L/S) mice, were unaffected. Neuritic dystrophy,
      however, was readily apparent in the basal forebrain, hippocampus and cortex, and
      was significantly reduced by LM11A-31, with no effect on amyloid levels. These
      studies reveal that p75(NTR) is an important and tractable in vivo drug target
      for AD, with LM11A-31 representing a novel class of therapeutic candidates.

PMID- 23545425
TI  - Effect of high-fat diet on metabolic indices, cognition, and neuronal physiology
      in aging F344 rats.
AB  - The prevalence of obesity and type 2 diabetes increases with age. Despite this,
      few studies have examined these conditions simultaneously in aged animals, and
      fewer studies have measured the impact of these conditions on brain function.
      Using an established animal model of brain aging (F344 rats), we investigated
      whether a high-fat diet (HFD) exacerbates cognitive decline and the hippocampal
      calcium-dependent afterhyperpolarization (a marker of age-dependent calcium
      dysregulation). Young and mid-aged animals were maintained on control or HFD for
      4.5 months, and peripheral metabolic variables, cognitive function, and
      electrophysiological responses to insulin in the hippocampus were measured. HFD
      increased lipid accumulation in the periphery, although overt diabetes did not
      develop, nor were spatial learning and memory altered. Hippocampal adiponectin
      levels were reduced in aging animals but were unaffected by HFD. For the first
      time, however, we show that the AHP is sensitive to insulin, and that this
      sensitivity is reduced by HFD. Interestingly, although peripheral glucose
      regulation was relatively insensitive to HFD, the brain appeared to show greater
      sensitivity to HFD in F344 rats.

PMID- 23545426
TI  - Androgen receptor gene and sex-specific Alzheimer's disease.
AB  - Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD)
      (onset at 65 years of age or older) compared with men. During perimenopausal
      years, women undergo hormonal changes that are accompanied by metabolic,
      cardiovascular, and inflammatory changes. These all together have been suggested
      as risk factors for late-onset AD. However, not all perimenopausal women develop
      AD; we hypothesize that certain genetic factors might underlie the increased
      susceptibility for developing AD in postmenopausal women. We investigated the
      Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients
      and normal control subjects by sequencing all coding exons and evaluating the
      length and distribution of the CAG repeat in exon 1. We could not establish a
      correlation between the repeat length, sex, and the disease status, nor did we
      identify possible pathogenic variants. AR is located on the X chromosome; to
      assess its role in AD, X-inactivation patterns will need to be studied to
      directly correlate the actual expressed repeat length to a possible sex-specific
      phenotypic effect.

PMID- 23545428
TI  - Comparison of the efficacy and safety of dual-opioid treatment with morphine plus
      oxycodone versus oxycodone/acetaminophen for moderate to severe acute pain after
      total knee arthroplasty.
AB  - BACKGROUND: In acute pain models, coadministration of low doses of morphine and
      oxycodone markedly enhanced analgesia relative to either opioid given alone.
      Enhanced analgesia with coadministration of morphine and oxycodone has also been
      reported in acute and chronic moderate to severe pain conditions during double
      blind studies. OBJECTIVE: The goal of this study was to compare the efficacy and
      tolerability of a flexible dose regimen of the morphine/oxycodone combination
      versus oxycodone/acetaminophen and fixed low-dose morphine/oxycodone. METHODS:
      This was a 5-center, randomized, open-label study of hospitalized patients (n =
      44) with acute moderate to severe postoperative pain after total knee
      arthroplasty. Inpatients were randomized to a flexible dose regimen of
      morphine/oxycodone (3 mg/2 mg to 24 mg/16 mg), fixed low-dose morphine/oxycodone
      regimen (3 mg/2 mg), or oxycodone/acetaminophen (5 mg/325 mg). Treatment was
      initiated following surgery after intravenous (IV) morphine patient-controlled
      analgesia. An algorithm was evaluated for converting the patient-controlled
      analgesia morphine dose to an initial oral dose of morphine/oxycodone. The
      primary efficacy variable was the time-weighted sum of pain intensity difference
      from 0 to 48 hours. RESULTS: The median values for the sum of the pain intensity
      difference from 0 to 48 hours for the morphine/oxycodone flexible dose and
      oxycodone/acetaminophen were similar and approximately twice that of fixed
      morphine/oxycodone 3 mg/2 mg (148.0, 139.5, and 71.3, respectively). Moderate to
      severe gastrointestinal adverse events occurred in 50% of patients in the
      oxycodone/acetaminophen group compared with 15% of the equianalgesic
      morphine/oxycodone group. On several items of the Brief Pain Inventory (general
      activity, walking ability, and sleep), the morphine/oxycodone flexible dose
      produced greater benefit than oxycodone/acetaminophen. CONCLUSIONS: Flexible dose
      morphine/oxycodone was superior to low-dose morphine/oxycodone and comparable to
      oxycodone/acetaminophen. Flexible dose morphine/oxycodone-treated patients had a
      lower rate of moderate to severe nausea or vomiting than equianalgesic
      oxycodone/acetaminophen-treated patients. Thus, morphine/oxycodone offers an
      attractive alternative to oxycodone/acetaminophen for the management of moderate
      to severe postoperative pain.

PMID- 23545427
TI  - The dominant role of inhibition in creating response selectivities for
      communication calls in the brainstem auditory system.
AB  - This review is concerned with how communication calls are processed and
      represented by populations of neurons in both the inferior colliculus (IC), the
      auditory midbrain nucleus, and the dorsal nucleus of the lateral lemniscus
      (DNLL), the nucleus just caudal to the IC. The review has five sections where
      focus in each section is on inhibition and its role in shaping response
      selectivity for communication calls. In the first section, the lack of response
      selectivity for calls in DNLL neurons is presented and discusses why inhibition
      plays virtually no role in shaping selectivity. In the second section, the lack
      of selectivity in the DNLL is contrasted with the high degree of response
      selectivity in the IC. The third section then reviews how inhibition in the IC
      shapes response selectivities for calls, and how those selectivities can create a
      population response with a distinctive response profile to a particular call,
      which differs from the population profile evoked by any other call. The fourth
      section is concerned with the specifics of inhibition in the IC, and how the
      interaction of excitation and inhibition creates directional selectivities for
      frequency modulations, one of the principal acoustic features of communication
      signals. The two major hypotheses for directional selectivity are presented. One
      is the timing hypothesis, which holds that the precise timing of excitation
      relative to inhibition is the feature that shapes directionality. The other
      hypothesis is that the relative magnitudes of excitation and inhibition are the
      dominant features that shape directionality, where timing is relatively
      unimportant. The final section then turns to the role of serotonin, a
      neuromodulator that can markedly change responses to calls in the IC. Serotonin
      provides a linkage between behavioral states and processing. This linkage is
      discussed in the final section together with the hypothesis that serotonin acts
      to enhances the contrast in the population responses to various calls over and
      above the distinctive population responses that were created by inhibition. This
      article is part of a Special Issue entitled "Communication Sounds and the Brain:
      New Directions and Perspectives". 

PMID- 23545429
TI  - Determination of stage interconversion in vitro and in vivo by construction of
      transgenic Toxoplasma gondii that stably express stage-specific fluorescent
      proteins.
AB  - Detection of Toxoplasma gondii conversion from the tachyzoite stage to the
      bradyzoite stage in living brain tissue is difficult because the parasites are
      small and conversion and reactivation of the parasites are transient events. To
      better understand the mechanisms of T. gondii stage conversion between
      tachyzoites and bradyzoites, and to recognize stage conversion in an intermediate
      host, we constructed a transgenic cyst-forming strain (PLK) of T. gondii. The
      parasites stably expressed enhanced green fluorescence protein (EGFP) in the
      tachyzoite stage and red fluorescence protein (RFP) in the bradyzoite stage,
      under the control of the SAG1 and BAG1 promoters, respectively. The resulting
      transgenic parasite was designated as PLK/Bi. The PLK/Bi zoites expressed only
      green fluorescence in the tachyzoite stage and only red fluorescence in the
      bradyzoite stage in vitro and in vivo. Fluorescence analyses showed that
      recombinant GFP and RFP were located to the intracellular vacuolar spaces. In
      addition, an analysis of growth and culture conditions of transgenic T. gondii
      was performed in vitro and the virulence was evaluated in vivo. Our data
      suggested that the stage-specific fluorescence expression by PLK/Bi may be
      rationally designed for in vitro and in vivo studies on stage conversion and
      reactivation of T. gondii.

PMID- 23545430
TI  - Minimally invasive papillary muscle sling placement during mitral valve repair in
      patients with functional mitral regurgitation.
AB  - BACKGROUND: We evaluated the safety and feasibility of minimally invasive mitral
      valve repair with papillary muscle sling placement via a right anterior
      thoracotomy approach in patients with severe functional mitral regurgitation
      (MR). METHODS: We retrospectively reviewed all minimally invasive mitral valve
      repairs with papillary muscle sling placement in patients with severe functional
      MR performed at our institution between October 2011 and September 2012. The
      operative times, lengths of stay, postoperative complications, and mortality were
      analyzed. RESULTS: We identified a total of 19 consecutive patients. There were
      12 men (63%); the mean age was 60 +/- 13 years. The mean +/- SD left ventricular
      ejection fraction was 23% +/- 5.5%, and 4 (21%) of the patients underwent
      previous coronary artery bypass graft surgery. The median aortic cross-clamp and
      cardiopulmonary bypass times were 106 (interquartile range [IQR], 76-120) and 163
      (IQR, 119-170) minutes, respectively. The median intensive care unit length of
      stay was 64 (IQR, 43-75) hours, and the median postoperative length of stay was 7
      (IQR, 5-7.5) days. Postoperatively, 2 patients developed acute kidney injury.
      There were no reoperations for bleeding or any cerebrovascular accidents. The 30
      day mortality was 0. A follow-up echocardiogram, obtained at a median of 3 (IQR,
      1-7.5) months, demonstrated none to trivial MR in all patients. CONCLUSIONS:
      Minimally invasive mitral repair with papillary muscle sling placement for severe
      functional MR is safe and effective in the short-term. Long-term data are needed
      to evaluate the effects on left ventricular remodeling and to assess the
      durability of the repair.

PMID- 23545431
TI  - An unusually fast developing giant saphenous vein graft aneurysm.

PMID- 23545432
TI  - Clarification of the intent of ventricular assist devices before patient consent.

PMID- 23545434
TI  - Spatial high resolution energy dispersive X-ray spectroscopy on thin lamellas.
AB  - For conventional samples and measurement geometries the spatial resolution of
      energy dispersive X-ray spectroscopy is limited by a tear drop shaped emission
      volume to about 1 MUm. This restriction can be substantially improved using thin
      samples and high acceleration voltage. In this contribution the spatial
      resolution of energy dispersive X-ray spectroscopy in a scanning electron
      microscope using thin lamella samples is investigated. At an acceleration voltage
      of 30 kV, an edge resolution down to Deltadedge = 40 +/- 10 nm is observed
      performing linescans across an interface, using an 80 nm thin sample prepared
      from a GaAs/AlAs-heterostructure. Furthermore, Monte-Carlo simulations of pure
      elements ranging from sodium to mercury are performed for different sample
      thicknesses. From the simulations we can derive a simple empirical formula to
      predict the spatial resolution as a function of sample thickness.

PMID- 23545433
TI  - Measurement of spatial coherence of electron beams by using a small selected-area
      aperture.
AB  - A new method for measuring the spatial coherence of an electron beam in a
      transmission electron microscope is proposed. In this method, an Airy pattern
      produced by a circular selected-area (SA) aperture with an effective diameter of
      several nanometers is analyzed to obtain the degree of coherence as a function of
      separation in the specimen plane. Using typical TEM illumination conditions,
      demonstrative measurements were carried out to determine the spatial coherence
      length, angular size of the electron source and shape of the coherence function.
      Based on the results, it was shown that the ratio of the spatial coherence length
      to the beam radius is about 5% for a condenser aperture with a diameter of 100
      MUm. This means that perfectly coherent illumination exists within the small SA
      aperture for beam diameters larger than 560 nm. As an example application of
      these results, the advantage of SA diffraction over nano-beam diffraction in
      electron diffractive imaging is discussed. The proposed method is unaffected by
      temporal coherence or geometric aberrations of the lenses. The possibility of
      carrying out future measurements using SA apertures with conventional sizes is
      also discussed.

PMID- 23545435
TI  - Molecular structure, electronic properties, NLO, NBO analysis and spectroscopic
      characterization of Gabapentin with experimental (FT-IR and FT-Raman) techniques
      and quantum chemical calculations.
AB  - Gabapentin (GP), structurally related to the neurotransmitter GABA (gamma
      aminobutyric acid), mimics the activity of GABA and is also widely used in
      neurology for the treatment of peripheral neuropathic pain. It exists in
      zwitterionic form in solid state. The present communication deals with the
      quantum chemical calculations of energies, geometrical structure and vibrational
      wavenumbers of GP using density functional (DFT/B3LYP) method with 6-311++G(d,p)
      basis set. In view of the fact that amino acids exist as zwitterions as well as
      in the neutral form depending on the environment (solvent, pH, etc.), molecular
      properties of both the zwitterionic and neutral form of GP have been analyzed.
      The fundamental vibrational wavenumbers as well as their intensities were
      calculated and compared with experimental FT-IR and FT-Raman spectra. The
      fundamental assignments were done on the basis of the total energy distribution
      (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM)
      method. The electric dipole moment, polarizability and the first
      hyperpolarizability values of the GP have been calculated at the same level of
      theory and basis set. The nonlinear optical (NLO) behavior of zwitterionic and
      neutral form has been compared. Stability of the molecule arising from hyper
      conjugative interactions and charge delocalization has been analyzed using
      natural bond orbital analysis. Ultraviolet-visible (UV-Vis) spectrum of the title
      molecule has also been calculated using TD-DFT method. The thermodynamic
      properties of both the zwitterionic and neutral form of GP at different
      temperatures have been calculated.

PMID- 23545436
TI  - Quantitative analysis of cefalexin based on artificial neural networks combined
      with modified genetic algorithm using short near-infrared spectroscopy.
AB  - In this paper, a novel chemometric method was developed for rapid, accurate, and
      quantitative analysis of cefalexin in samples. The experiments were carried out
      by using the short near-infrared spectroscopy coupled with artificial neural
      networks. In order to enhancing the predictive ability of artificial neural
      networks model, a modified genetic algorithm was used to select fixed number of
      wavelength.

PMID- 23545437
TI  - Synthesis and characterization of structural, optical, thermal and dielectric
      properties of polyaniline/CoFe2O4 nanocomposites with special reference to
      photocatalytic activity.
AB  - In this study we have synthesized polyaniline/CoFe2O4 nanocomposites (PANI@CFs)
      by in situ polymerization method with different amounts of the CoFe2O4
      nanoparticles NPs (CF-NPs) (0.5 g and 1.0 g). The structural optical, thermal and
      dielectric properties of the as synthesized PANI@CFs were studied. The XRD
      analysis ensures that CF-NPs have a single phase spinel structure. The XRD and
      EDAX results confirmed that the CF-NPs were successfully incorporated in the PANI
      matrix. The crystalline size analysis revealed that the size increased with
      increasing CF-NPs amount in the PANI@CFs, because of the aggregation effect. TGA
      exhibited an enhanced thermal stability of the PANI@CFs as compare with PANI
      owing to the strong interaction between the CF-NPs and polymer matrix. The energy
      band gaps as calculated through the Tauc relation were found to be gradually
      higher with the increasing the amount of CF-NPs in PANI@CFs. The dielectric
      constants (epsilon', epsilon"), dielectric loss (tandelta) and AC conductivity
      (sigmaac) were studied as the function of frequency and composition, which have
      been explained by 'Maxwell Wagner Model'. The high dielectric constant and ac
      conductivity were observed of PANI@CFs than PANI. Moreover, PANI@CF 1:2 exhibited
      the promising photocatalytic activity for the photo-decoloration of the methyl
      orange (MO) dye under UV light irradiation. Results also showed protection of
      photo-decoloration of the MO dye by the disodium ethylenediaminetetraacetate
      dehydrate (EDTA-Na2; C10H14N2Na2O8.2H2O) (hole scavenger) and tert-butyl alcohol
      (C4H10O) (radical scavenger) clearly suggested the implication of reactive oxygen
      species (ROS) in the photocatalytic activity of PANI@CF 1:2. It is encouraging to
      conclude that PANI@CF bears the potential of its applications in photocatalysis.

PMID- 23545438
TI  - Upper limb automatisms differ quantitatively in temporal and frontal lobe
      epilepsies.
AB  - We quantitatively evaluated the localizing and lateralizing characteristics of
      ictal upper limb automatisms (ULAs) in patients with temporal lobe epilepsy (TLE;
      n=38) and frontal lobe epilepsy (FLE; n=20). Movement speed, extent, length, and
      duration of ULAs were quantitatively analyzed with motion capturing techniques.
      Upper limb automatisms had a larger extent (p<0.001), covered more distance
      (p<0.05), and were faster (p<0.001) in FLE than in TLE. In TLE, the maximum speed
      of ULAs was higher ipsilaterally than contralaterally (173 vs. 84pixels/s;
      p=0.02), with no significant difference in FLE (511 vs. 428). The duration of
      ictal automatisms in relation to the total seizure duration was shorter in TLE
      than in FLE (median 36% vs. 63%; p<0.001), with no difference in the absolute
      duration (26s vs. 27s). These results demonstrate that quantitative movement
      analysis of ULAs differentiates FLE from TLE, which may aid in the localization
      of the epileptogenic zone.

PMID- 23545440
TI  - The interplay between microevolution and community structure in microbial
      populations.
AB  - The structure of microbial communities is key to their functionality. However,
      this structure is likely to be influenced by adaptive genetic change in members
      of the community, which can occur over a matter of days. Changes in community
      structure can in turn influence the evolutionary trajectories of species within
      the community, further altering community structure. Microbial communities
      provide evidence for this interplay between rapid evolution and community
      structure. To date, studies are primarily limited to simple in vitro systems, but
      we suggest similar processes are inevitably operating in both natural and derived
      communities, which are important for biotechnology. 

PMID- 23545441
TI  - Engineering synthetic hydrogel microenvironments to instruct stem cells.
AB  - Advances in our understanding and ability to manipulate stem cell behavior are
      helping to move stem cell-based therapies toward the clinic. However, much of our
      knowledge has been gained from standard 2-dimensional culture systems, which
      often misrepresent many of the signals that stem cells receive in their native 3
      dimensional environments. Fortunately, the field of synthetic hydrogels is
      developing to better recapitulate many of these signals to guide stem cell
      behavior, both as in vitro models and as delivery vehicles for in vivo
      implantation. These include a multitude of structural and biochemical cues that
      can be presented on the cellular scale, such as degradation, adhesion, mechanical
      signals, topography, and the presentation of growth factors, often with precise
      spatiotemporal control.

PMID- 23545442
TI  - Enzyme and metabolic engineering for the production of novel biopolymers:
      crossover of biological and chemical processes.
AB  - The development of synthetic biology has transformed microbes into useful
      factories for producing valuable polymers and/or their precursors from renewable
      biomass. Recent progress at the interface of chemistry and biology has enabled
      the production of a variety of new biopolymers with properties that substantially
      differ from their petroleum-derived counterparts. This review touches on recent
      trials and achievements in the field of biopolymer synthesis, including chemo
      enzymatically synthesized aliphatic polyesters, wholly biosynthesized lactate
      based polyesters, polyhydroxyalkanoates and other unusual bacterially synthesized
      polyesters. The expanding diversities in structure and the material properties of
      biopolymers are key for exploring practical applications. The enzyme and
      metabolic engineering approaches toward this goal are discussed by shedding light
      on the successful case studies. 

PMID- 23545439
TI  - Optic neuritis in neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is an autoimmune demyelinating disease associated with
      recurrent episodes of optic neuritis and transverse myelitis, often resulting in
      permanent blindness and/or paralysis. The discovery of autoantibodies (AQP4-IgG)
      that target aquaporin-4 (AQP4) has accelerated our understanding of the cellular
      mechanisms driving NMO pathogenesis. AQP4 is a bidirectional water channel
      expressed on the plasma membranes of astrocytes, retinal Muller cells, skeletal
      muscle, and some epithelial cells in kidney, lung and the gastrointestinal tract.
      AQP4 tetramers form regular supramolecular assemblies at the cell plasma membrane
      called orthogonal arrays of particles. The pathological features of NMO include
      perivascular deposition of immunoglobulin and activated complement, loss of
      astrocytic AQP4, inflammatory infiltration with granulocyte and macrophage
      accumulation, and demyelination with axon loss. Current evidence supports a
      causative role of AQP4-IgG in NMO, in which binding of AQP4-IgG to AQP4
      orthogonal arrays on astrocytes initiates complement-dependent and antibody
      dependent cell-mediated cytotoxicity and inflammation. Immunosuppression and
      plasma exchange are the mainstays of therapy for NMO optic neuritis. Novel
      therapeutics targeting specific steps in NMO pathogenesis are entering the
      development pipeline, including blockers of AQP4-IgG binding to AQP4 and
      inhibitors of granulocyte function. However, much work remains in understanding
      the unique susceptibility of the optic nerves in NMO, in developing animal models
      of NMO optic neuritis, and in improving therapies to preserve vision. 

PMID- 23545443
TI  - Preventive antioxidant responses to extreme oxygen level fluctuation in a
      subterranean crustacean.
AB  - The principal aim of this work was to explore the responses of the groundwater
      crustacean Niphargus rhenorhodanensis to oxidative stress caused by short- and
      long-term drastic variations in oxygen level. To this end, we investigated
      thiobarbituric acid reactive substances (TBARS) levels and anti-oxidative enzyme
      (SOD and GPx) activities during 24 h anoxia and post-anoxia recovery, and during
      10 days of severe hypoxia and post-hypoxia recovery. We observed a decrease in
      TBARS amounts during recovery from severe hypoxia. Parallel to these results, we
      observed an overactivation of SOD activity after a 24 h anoxic stress. GPx
      activity measured at the end of anoxia or severe hypoxia and in the early hours
      of post-stress recovery also showed an overactivation compared to the control
      group. We can hypothesize that this overproduction of GPx corresponded to an
      anticipatory mechanism coping with the overproduction of reactive oxygen species
      (ROS) during the recovery phase in subterranean animals. This response could be
      considered as a major asset for life in alternately normoxic and hypoxic
      conditions, and therefore in extreme biotopes such as groundwaters.

PMID- 23545444
TI  - The relationship between energy expenditure and speed during pedestrian
      locomotion in birds: a morphological basis for the elevated y-intercept?
AB  - The slope of the typically linear relationship between metabolic rate and walking
      speed represents the net cost of transport (NCOT). The extrapolated y-intercept
      is often greater than resting metabolic rate, thus representing a fixed cost
      associated with pedestrian transport including body maintenance costs. The full
      cause of the elevated y-intercept remains elusive and it could simply represent
      experimental stresses. The present literature-based study compares the mass
      independent energetic cost of pedestrian locomotion in birds (excluding those
      with an upright posture, i.e. penguins), represented by the y-intercept, to a
      known predictor of cost of transport, hip height. Both phylogenetically informed
      and non-phylogenetically informed analyses were undertaken to determine if
      patterns of association between hip height, body mass, and the y-intercept are
      robust with respect to the method of analysis. Body mass and hip height were
      significant predictors of the y-intercept in the best phylogenetically-informed
      and non-phylogenetically informed models. Thus there is evidence that, in birds
      at least, the elevated y-intercept is a legitimate component of locomotion energy
      expenditure. Hip height is probably a good proxy of effective limb length and
      thus perhaps birds with greater hip heights have lower y-intercepts because their
      longer legs more efficiently accommodate body motion and/or because their limbs
      are more aligned with the ground reaction forces.

PMID- 23545445
TI  - Improved protocol for isolation of Campylobacter spp. from retail broiler meat
      and use of pulsed field gel electrophoresis for the typing of isolates.
AB  - To improve the detection of Campylobacter spp. in retail broiler meat, a
      reference method (R subsamples) based on the enrichment of 25 g of meat in Bolton
      broth at 42 degrees C under microaerobiosis was compared with an alternative
      method (A subsamples) consisting in the rinsing of meat samples for 30s in
      buffered peptone water with antimicrobials with incubation at 42 degrees C under
      aerobiosis. One piece of meat (breasts, tenderloins and thighs) was rinse in
      experiment 1 (A1) and two pieces in experiment 2 (A2). Campylobacter spp. were
      isolated on agar plates and identified by PCR. Retail samples in Alabama had less
      prevalence (P <= 0.05) than samples in the state of Washington. The percentage of
      positive was higher (P <= 0.05) in A than in R subsamples and rinsing two pieces
      of meat yielded the highest percentage of positive subsamples. R subsamples
      showed variations in the prevalence by product. However, A subsamples had similar
      prevalence of positives among products compare to the result from reference
      method. More Campylobacter coli isolates were collected in A2 subsamples. Pulse
      field gel electrophoresis (PFGE) was used as subtyping method to study the genome
      similarity among the isolates from all methods. A larger diversity of isolates
      were detected by PFGE in A2 subsamples. Denaturing gradient gel electrophoresis
      analysis suggested that the initial bacterial populations of the meat samples
      impact the final bacterial profile after enrichment. Rinsing broiler meats was
      less time consuming, required less sample preparation and was more sensitive than
      the reference method for the isolation of naturally occurring Campylobacter spp.
      This new method could help with epidemiological and intervention studies to
      control Campylobacter spp.

PMID- 23545446
TI  - New opportunities for improved ribotyping of C. difficile clinical isolates by
      exploring their genomes.
AB  - Clostridium difficile causes outbreaks of infectious diarrhoea, most commonly
      occurring in healthcare institutions. Recently, concern has been raised with
      reports of C. difficile disease in those traditionally thought to be at low risk
      i.e. community acquired rather than healthcare acquired. This has increased
      awareness for the need to track outbreaks and PCR-ribotyping has found widespread
      use to elucidate epidemiologically linked isolates. PCR-ribotyping uses conserved
      regions of the 16S rRNA gene and 23S rRNA gene as primer binding sites to produce
      varying PCR products due to the intergenic spacer (ITS1) regions of the multiple
      operons. With the explosion of whole genome sequence data it became possible to
      analyse the start of the 23S rRNA gene for a more accurate selection of regions
      closer to the end of the ITS1. However the following questions must still be
      asked: (i) Does the chromosomal organisation of the rrn operon vary between C.
      difficile strains? and (ii) just how conserved are the primer binding regions?
      Eight published C. difficile genomes have been aligned to produce a detailed
      database of indels of the ITS1's from the rrn operon sets. An iPad Filemaker Go
      App has been constructed and named RiboTyping (RT). It contains detail such as
      sequences, ribotypes, strain numbers, GenBank numbers and genome position
      numbers. Access to various levels of the database is provided so that details can
      be printed. There are three main regions of the rrn operon that have been
      analysed by the database and related to each other by strain, ribotype and
      operon: (1) 16S gene (2) ITS1 indels (3) 23S gene. This has enabled direct intra-
      and inter-genomic comparisons at the strain, ribotype and operon (allele) levels
      in each of the three genomic regions. This is the first time that such an
      analysis has been done. By using the RT App with search criteria it will be
      possible to select probe combinations for specific strains/ribotypes/rrn operons
      for experiments to do with diagnostics, typing and recombination of operons. Many
      more incomplete C. difficile whole genome sequencing projects are recorded in
      GenBank as underway and the rrn operon information from these can also be added
      to the RT App when available. The RT App will help simplify probe selection
      because of the complexity of the ITS1 in C. difficile even in a single genome and
      because other allele-specific regions (16S and 23S genes) of variability can be
      relationally compared to design extra probes to increase sensitivity.

PMID- 23545448
TI  - An easy, quick and cheap high-throughput method for yeast DNA extraction from
      microwell plates.
AB  - We herein present a high-throughput and cheap method for yeast DNA isolation in a
      96 well microplate. About 1500 yeast isolates can be processed within one working
      day and final DNA concentrations are suitable for direct application in PCR-based
      molecular typing methods.

PMID- 23545447
TI  - Simultaneous detection of Salmonella pathogenicity island 2 and its antibiotic
      resistance genes from seafood.
AB  - Salmonella enterica serovars are virulent pathogens of humans and animals with
      many strains possessing multiple drug resistance traits. They have been found to
      carry resistance to ampicillin, chloramphenicol, florfenicol, streptomycin,
      sulfonamides, and tetracycline (ACSSuT-resistant). A rapid and sensitive
      multiplex PCR (mPCR)-based assay was developed for the detection of Salmonella
      serovars from seafood. Six sets of primers which are one primer pair targeting
      Salmonella specific gene invA (284 bp), two Salmonella pathogenicity island 2
      (SPI-2) genes ssaT (780 bp) and sseF (888 bp) and three antibiotic resistance
      genes floR (198 bp), sul1 (425 bp), tetG (550 bp) were used for the study. The
      specificity and sensitivity of the assay were tested by spiking shrimp/fish/clam
      homogenate with viable cells of Salmonella. This assay allows for the cost
      effective and reliable detection of pathogenic Salmonella enterica from seafood.
      The mPCR developed in the present study proved to be a potent analytical tool for
      the rapid identification of multidrug-resistant Salmonella serovars from seafood.

PMID- 23545449
TI  - Virulence gene typing of methicillin-resistant Staphylococcus aureus as a
      complement in epidemiological typing.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has widely spread to all parts
      of the world. For surveillance and effective infection control molecular typing
      is required. We have evaluated the utility of virulence gene determination as a
      complementary tool for epidemiological typing of MRSA in relation to spa-typing
      and pulsed-field gel electrophoresis (PFGE). We assessed 63 community-acquired
      MRSA (CA-MRSA) isolates detected in the West part of Sweden for 30 virulence
      factor genes (VF) and agr allele variations by serial polymerase chain reaction
      (PCR) assays. These isolates belonged to sequence types (ST) 8, 80, 45 and 30 as
      classified by multilocus sequence typing. The isolates in each spa-type and PFGE
      type were examined over an extended time-period and constituted a varying number
      of PFGE-subtypes (5-14) and spa-types (3-11) within four major PFGE types. Each
      ST had a unique VF profile. For isolates within a major PFGE type showing high
      diversity both in PFGE subtypes and spa the VF profile varied as well in contrast
      to those with low diversity where no alterations were seen. Thus, the accuracy of
      each typing method does not only vary by the method per se but is rather
      dependent on the genetic repertoire of the typed strains and genes evaluated. For
      strains demonstrating high diversity VF typing may be a useful complement in the
      epidemiological investigations, and may highlight the accurate discriminatory
      power of spa or PFGE typing.

PMID- 23545450
TI  - Community college students with learning disabilities: evidence of impairment,
      possible misclassification, and a documentation disconnect.
AB  - Recent research suggests that most 4-year college students diagnosed with
      specific learning disability (SLD) do not meet objective criteria for the
      disorder, show normative deficits in academic skills, or have childhood histories
      of SLD. The purpose of this study was to examine the functioning of students
      diagnosed with SLD attending community college. We reviewed SLD documentation for
      359 community college students previously diagnosed with SLD and receiving
      academic accommodations. Most students met objective criteria (82.3%) and were
      first diagnosed in childhood (93.3%). Most students also showed average
      intellectual functioning and below-average to borderline academic achievement.
      However, 27.3% showed uniformly low ability and achievement scores, suggesting
      possible misclassification. Students who failed to meet objective criteria for
      SLD often submitted test data that lacked current, adult-normed standardized test
      scores; many were diagnosed based on response to intervention and submitted only
      an individualized education program or summary of performance. This finding
      provides initial evidence of a disconnect between the qualitative documentation
      that secondary schools provide and the quantitative documentation that
      postsecondary institutions require for SLD classification. 

PMID- 23545451
TI  - Diagnostic performance of qualitative shear-wave elastography according to
      different color map opacities for breast masses.
AB  - PURPOSE: To compare the diagnostic performance of qualitative shear-wave
      elastography (SWE) according to three different color map opacities for breast
      masses MATERIALS AND METHODS: 101 patients aged 21-77 years with 113 breast
      masses underwent B-mode US and SWE under three different color map opacities
      (50%, 19% and 100%) before biopsy or surgery. Following SWE features were
      reviewed: visual pattern classification (pattern 1-4), color homogeneity (Ehomo)
      and six-point color score of maximum elasticity (Ecol). Combined with B-mode US
      and SWE, the likelihood of malignancy (LOM) was also scored. The area under the
      curve (AUC) was obtained by ROC curve analysis to assess the diagnostic
      performance under each color opacity. RESULTS: A visual color pattern, Ehomo,
      Ecol and LOM scoring were significantly different between benign and malignant
      lesions under all color opacities (P<0.001). For 50% opacity, AUCs of visual
      color pattern, Ecol, Ehomo and LOM scoring were 0.902, 0.951, 0.835 and 0.975.
      But, for each SWE feature, there was no significant difference in the AUC among
      three different color opacities. For all color opacities, visual color pattern
      and Ecol showed significantly higher AUC than Ehomo. In addition, a combined set
      of B-mode US and SWE showed significantly higher AUC than SWE alone for color
      patterns, Ehomo, but no significant difference was found in Ecol. CONCLUSION:
      Qualitative SWE was useful to differentiate benign from malignant breast lesion
      under all color opacities. The difference in color map opacity did not
      significantly influence diagnostic performance of SWE.

PMID- 23545453
TI  - The effect of personality traits and psychosocial training on burnout syndrome
      among healthcare students.
AB  - AIMS: The aims of this paper were to explore the influence of personality factors
      on student burnout syndrome and to explore the effect of psychosocial training on
      burnout and personality predictors among university students in health care
      professions. DESIGN AND METHOD: A quasi-experimental pre-test/post-test design
      was used to evaluate the effect of psychosocial training. A sample of 111
      university students were divided into experimental and control groups (average
      age 20.7 years, SD=2.8 years; 86.1% females). The School Burnout Inventory (SBI),
      Sense of Coherence (SOC) questionnaire, and Rosenberg's Self-esteem scale were
      employed. Linear regression and analysis of variance were applied for statistical
      analysis. RESULTS: The results show that socio-psychological training had a
      positive impact on the level of burnout and on personality factors that are
      related to burnout. After completing the training, the level of burnout in the
      experimental group significantly decreased (95% confidence interval: 0.93, 9.25),
      and no significant change was observed in the control group. Furthermore,
      respondents' sense of coherence increased in the experimental group (95%
      confidence interval: -9.11, 2.64), but there were no significant changes in
      respondents' self-esteem levels in either group. CONCLUSIONS: Psychosocial
      training positively influenced burnout among students in health care professions.
      Because the coping strategies that were used during the study are similar to
      effective work coping strategies, psychosocial training can be considered to be
      an effective tool to prevent burnout in the helping professions.

PMID- 23545452
TI  - Antigenic peptide trimming by ER aminopeptidases--insights from structural
      studies.
AB  - Generation and destruction of antigenic peptides by ER resident aminopeptidases
      ERAP1 and ERAP2 have been shown in the last few years to be important for the
      correct functioning and regulation of the adaptive immune response. These two
      highly homologous aminopeptidases appear to have evolved complex mechanisms well
      suited for their biological role in antigen presentation. Furthermore,
      polymorphic variability in these enzymes appears to affect their function and
      predispose individuals to disease. This review discusses our current
      understanding of the molecular mechanisms behind ERAP1/2 function as suggested by
      several recently determined crystallographic structures of these enzymes.

PMID- 23545454
TI  - Antioxidant and anti-inflammatory activities of the phenolic extracts of Sapium
      sebiferum (L.) Roxb. leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Sapium sebiferum have long been
      used in Traditional Chinese Medicine (TCM) for the treatment of eczema, shingles,
      edema, swelling, ascites, scabs, and snakebites, among other maladies. AIM OF
      THIS STUDY: The present study aimed to investigate the antioxidant and anti
      inflammatory effects of the phenolic extracts of Sapium sebiferum leaves using in
      vitro and in vivo models. MATERIALS AND METHODS: The in vitro antioxidant
      activities of the extracts were measured using common chemical methods (total
      phenolic content; total flavonoid content; scavenging of DPPH., ABTS+.,
      superoxide, and nitrite radicals; reducing power; beta-carotene bleaching; and
      FTC assays). The in vivo topical anti-inflammatory activities were tested using
      the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis animal model.
      The SOD and CAT activities and the GSH content of ear tissue were also determined
      using test kits. RESULTS: The extracts of Sapium sebiferum leaves exhibited
      strong in vitro antioxidant activities. They also showed significant (P<0.001)
      and dose-dependent anti-inflammatory activities in an acute dermatitis model at
      the doses of 0.03 mg/ear, 0.1mg/ear, and 0.3mg/ear. The application of Sapium
      sebiferum leaf extracts increased the SOD and CAT activities and the GSH content
      relative to those of the TPA treatment group. The anti-inflammatory effect of the
      Sapium sebiferum leaf extract was positively correlated with its antioxidant
      activity. CONCLUSION: These results demonstrate that Sapium sebiferum leaf
      extract is an effective anti-inflammatory agent in the TPA-induced dermatitis
      model, and its anti-inflammatory effect is related, at least in part, to its
      antioxidant activity.

PMID- 23545455
TI  - Ginsenoside Re reduces insulin resistance through activation of PPAR-gamma
      pathway and inhibition of TNF-alpha production.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng is a well-known traditional Chinese
      medicine and has been used for treatment of various diseases for more than four
      thousand years in Asia. Ginseng saponins or ginsenosides, the active constituents
      are reported to possess antidiabetic activity, but their antihyperglycemic
      mechanisms are not fully elucidated. In the present study, the mechanisms of
      action of ginsenoside Re were investigated in vitro models. MATERIALS AND
      METHODS: 3T3-L1 cells were chosen as the model to investigate the molecular
      mechanisms of action of ginsenoside Re. Influence of ginsenoside Re on the
      adipogenesis was examined by determining TG levels in 3T3-L1 adipocytes by the
      method of TG oxidation enzyme. Glucose uptake in 3T3-L1 cells stimulated by
      insulin in the absence or presence of ginsenoside Re were quantified by measuring
      (3)H-2-deoxy-d-glucose levels. Cytokine proteins released into the medium
      including adiponectin and TNF-alpha were tested using respective ELISA kits. In
      addition, real time RT-PCR was conducted to investigate the expression changes of
      PPAR-gamma and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF
      alpha. And western blot analysis was performed to determine the translocation of
      GLUT4. Finally, effects of ginsenoside Re on NO production in 3T3-L1 adipocytes
      and in macrophages were investigated through measurement of nitrite concentration
      by Griess reagent. RESULTS: Ginsenoside Re induced adipogenesis of 3T3-L1
      adipocytes by accumulating TG, increased glucose uptake and up-regulated PPAR
      gamma2, IRS-1, ap2 and adiponectin genes expressions. Meanwhile, Re also
      increased production and release of adiponectin. Although having no effects on
      GLUT4 gene expression, Re facilitated GLUT4 protein translocation to the
      membranes. In addition, Re inhibited the expression and release of TNF-alpha.
      Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells
      stimulated by LPS, TNF-alpha and IFN-gamma and in LPS-stimulated mouse peritoneal
      macrophages. CONCLUSIONS: Ginsenoside Re exhibited the action of reducing insulin
      resistance through activation of PPAR-gamma pathway by directly increasing the
      expressions of PPAR-gamma2 and its responsive genes, adiponectin, IRS-1, ap2,
      inhibiting TNF-alpha production and facilitating the translocation of GLUT4 to
      promote glucose uptake and disposal in 3T3-L1 adipocytes.

PMID- 23545456
TI  - Antimicrobial activity of southern African medicinal plants with dermatological
      relevance: From an ethnopharmacological screening approach, to combination
      studies and the isolation of a bioactive compound.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical reports on more than 100 southern
      African medicinal plants with dermatological relevance have been highlighted, yet
      there is still limited scientific data to support claims for their antimicrobial
      effectiveness against skin pathogens. Guided by ethnobotanical data, this paper
      explores the antimicrobial efficacies of southern African medicinal plants used
      to treat skin ailments. AIM OF THE STUDY: To investigate the antimicrobial
      properties of southern African medicinal plants against dermatologically relevant
      pathogens. The study also aimed at providing a scientific rationale for the
      traditional use of plant combinations to treat skin diseases and the isolation of
      the bio-active compound from the most active species, Aristea ecklonii
      (Iridaceae). MATERIALS AND METHODS: Organic and aqueous extracts (132) were
      prepared from 47 plant species and screened for antimicrobial properties against
      dermatologically relevant pathogens using the micro-titre plate dilution method.
      Four different plant combinations were investigated for interactive properties
      and the sum of the fractional inhibitory concentration (?FIC) calculated.
      Isobolograms were used to further investigate the antimicrobial interactive
      properties of Pentanisia prunelloides combined with Elephantorrhiza elephantina
      at varied ratios. A bioactivity-guided fractionation process was adopted to
      fractionate the organic leaf extract of Aristea ecklonii. RESULTS: Plants
      demonstrating notable broad-spectrum activities (MIC values <=1.00mg/ml) against
      the tested pathogens included extracts from Aristea ecklonii, Chenopodium
      ambrosioides, Diospyros mespiliformis, Elephantorrhiza elephantina, Eucalyptus
      camaldulensis, Gunnera perpensa, Harpephyllum caffrum, Hypericum perforatum,
      Melianthus comosus, Terminalia sericea and Warburgia salutaris. The organic
      extract of Elephantorrhiza elephantina, a plant reportedly used to treat acne
      vulgaris, demonstrated noteworthy antimicrobial activity (MIC value of 0.05mg/ml)
      against Propionibacterium acnes. Similarly, Diospyros mespiliformis reported for
      its traditional use to treat ringworm, also displayed noteworthy antimicrobial
      activity against Trichophyton mentagrophytes (MIC 0.10mg/ml) and Microsporum
      canis (MIC 0.50mg/ml). The aqueous root extracts of Pentanisia prunelloides
      combined (1:1) with Elephantorrhiza elephantina displayed synergistic
      interactions (?FIC values 0.31-0.38) against Staphylococcus aureus, gentamycin
      methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis and
      Candida albicans. Fractionation of Aristea ecklonii resulted in the isolation of
      the known bio-active compound, plumbagin, displaying noteworthy antimicrobial
      activity (MIC range between 2.00MUg/ml and 16.00MUg/ml). CONCLUSION: Most of the
      plant extracts demonstrated pathogen specific antimicrobial effects with a few
      exhibiting broad-spectrum activities. Positive antimicrobial effects noted for
      plants such as Elephantorrhiza elephantina and Diospyros mespiliformis used for
      acne vulgaris and ringworm infections, respectively, give some validation to
      their reported traditiona l uses. Synergistic interactions noted for Pentanisia
      prunelloides combined with Elephantorrhiza elephantina validate an enhanced
      antimicrobial effect when used in combination. Noteworthy antimicrobial
      activities (MIC range between 2.00MUg/ml and 16.00MUg/ml) were observed for
      plumbagin isolated from Aristea ecklonii.

PMID- 23545457
TI  - Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration
      of Ajuga decumbens Thunb extract in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ajuga decumbens Thunb is a medicinal plant native
      to China popularly used to treat chronic pelvic inflammation and hysteromyoma.
      Its main bioactive components are iridoid glycosides, such as 8-O-acetylharpagide
      and harpagide that had presented antibacterial, anti-inflammatory, and antiviral
      activities. AIM OF THE STUDY: To establish a sensitive LC-MS/MS method and
      compare the pharmacokinetics of 8-O-acetylharpagide and harpagide in rats after
      oral administration of their pure forms and from compounds obtained from Ajuga
      decumbens extract. MATERIALS AND METHODS: Rats received orally 15 mg/kg
      (equivalent of 6 mg/kg 8-O-acetylharpagide and 1.5mg/kg harpagide), 30 mg/kg and
      60 mg/kg of Ajuga decumbens Thunb extract and were compared to animals that
      received 12 mg/kg of 8-O-acetylharpagide or 3mg/kg of harpagide p.o.
      Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by
      LC-MS/MS method at different time points and all pharmacokinetic parameters were
      estimated by non-compartmental analysis. RESULTS: Results showed that the iridoid
      glycosides were quickly absorbed by oral route and showed a dose-dependence
      profile. Pharmacokinetic parameters of both glycosides were essentially the same
      except Tmax when dosed as the extract or pure forms. CONCLUSION: 8-O
      acetylharpagide was metabolized to harpagide, which affected the pharmacokinetic
      profiles of harpagide when dosed as the extract. This pharmacokinetic study seems
      to be useful for a further clinical study of Ajuga decumbens Thunb extract.

PMID- 23545459
TI  - Bitterness values for traditional tonic plants of southern Africa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bitterness values have been determined for
      southern African plant species that are traditionally used as tonics (imbizas or
      'musa-pelo) to alleviate the symptoms of stress and a variety of ailments related
      to the digestive system. AIM OF THE STUDY: To measure and present, for the first
      time, the bitterness values of 15 of the best-known and most widely used tonic
      plants in southern Africa in order to find a rationale for their traditional use
      in improving appetite and treating digestive ailments. RESULTS: Most of the
      plants were found to be very bitter, with bitterness values comparable to those
      reported for internationally well-known bitter tonics such as Artemisia
      absynthium L. and Gentiana lutea L. CONCLUSIONS: The relatively high bitterness
      values obtained for all of the plants indicate that their alleged value in
      improving digestion and appetite may at least be partly ascribed to the bitter
      tonic (amarum) effect, i.e., the stimulation of gastric juices via the nervus
      vagus. It may be interesting to examine the chemical compounds responsible for
      the bitter taste, as well as the possible links between bitterness and the
      anecdotal anti-stress properties ascribed to these species.

PMID- 23545460
TI  - Ontogeny of pronounced female-biased sexual size dimorphism in the Malaysian cat
      gecko (Aeluroscalabotes felinus: Squamata: Eublepharidae): a test of the role of
      testosterone in growth regulation.
AB  - Species differences in the effect of male gonadal androgens on male growth are
      considered a possible mechanism allowing shifts in magnitude and even direction
      of sexual size dimorphism (SSD) in squamate reptiles. According to the
      bipotential growth regulation hypothesis, the androgen testosterone (T) enhances
      male growth in species with male-biased SSD and conversely inhibits male growth
      in males of female-larger species. In the present study, we describe the ontogeny
      of the pronounced female-biased SSD and report the effect of T on growth via
      hormonal manipulations in males and females of the Malaysian cat gecko
      (Aeluroscalabotes felinus). In accord with the predictions of the bipotential
      growth regulation hypothesis, growth was inhibited by replacement of T in
      castrated males. Additionally, exogenous T inhibited growth of females to male
      typical levels. Nevertheless, male castration alone did not significantly affect
      growth, contrary to the prediction of the bipotential growth regulation
      hypothesis, which contradicts the generality of this hypothesis. Application of
      exogenous T to females can interfere with normal ovarian function. Therefore,
      although not directly tested in this study, we suggest that ovarian effects on
      the ontogeny of SSD in A. felinus are consistent with our results. The
      development of SSD is a function of differential growth between the sexes, and
      potential sex-specific growth regulation in both males and females should be
      taken into account as possible proximate mechanisms responsible for SSD.

PMID- 23545458
TI  - Total saponins of Panax notoginseng enhance VEGF and relative receptors signals
      and promote angiogenesis derived from rat bone marrow mesenchymal stem cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Total saponins of Panax notoginseng (tPNS), main
      constituents extracted from Panax Notoginseng, a highly valued traditional
      Chinese medicine, has been shown to increase protein expression and the secretion
      of vascular endothelial growth factor (VEGF) in human umbilical vein endothelial
      cells. AIMS OF THE STUDY: The effects of tPNS on angiogenesis were studied in rat
      bone marrow mesenchymal stem cells (rBMSCs). MATERIALS AND METHODS: rBMSCs were
      stimulated by tPNS of 48 h. The mRNA expression levels of VEGF-A, Flt-1 and Kdr
      in rBMSCs were determined by quantitative real time PCR (qRT-PCR). rBMSCs were
      induced to differentiate into endothelial-like cells and the effects of tPNS on
      the angiogenesis ability of rBMSCs and rBMSCs after endothelial differentiation
      were assayed by a Matrigel model in vivo and in vitro. RESULTS: tPNS (100 MUg/ml)
      significantly enhanced the mRNA expression level of VEGF-A and Kdr compared to
      the control group, while they had no obvious effect on the expression of Flt-1.
      tPNS (1 MUg/ml and 100 MUg/ml) significantly increased capillary network forming
      of rBMSCs after endothelial differentiation in Matrigel in vitro. tPNS (50
      MUg/kg, 100 MUg/kg and 150 MUg/kg) also significantly increased angiogenesis
      induced by the combination with implantation of rBMSCs and Matrigel in vivo.
      CONCLUSION: tPNS up-regulate VEGF-A and Kdr expression, and promote angiogenesis
      in rat bone marrow mesenchymal stem cells.

PMID- 23545461
TI  - Prospective-triggered sequential dual-source end-systolic coronary CT angiography
      for patients with atrial fibrillation: a feasibility study.
AB  - BACKGROUND: Obtaining diagnostic coronary CT angiography with low radiation
      exposure in patients with irregular heart rhythms such as atrial fibrillation
      (AF) remains challenging. OBJECTIVE: We evaluated image quality and inter-reader
      variability with the use of prospective electrocardiographic (ECG)-triggered
      sequential dual-source acquisition at end systole for coronary artery disease
      (CAD) evaluation in patients with AF. METHODS: Thirty consecutive patients with
      AF who underwent prospective ECG-triggered sequential dual-source acquisition
      were evaluated. Images were reconstructed every 50 milliseconds from 250 to 400
      milliseconds after the R wave. Two independent, blinded readers evaluated the
      coronaries for image quality on a 5-point scale (worst to best) and stenosis on 5
      point semiquantitative (none to severe) and binary scales (>50% or <50%).
      Diagnostic image quality was graded for each reconstruction. RESULTS: Eleven
      patients (37%) had significant (>=50% stenosis) CAD. Average heart rate was 82 +/
      20 beats/min and variability range was 71 +/- 22 beats/min. Mean effective
      radiation dose was 6.5 +/- 2.4 mSv. Diagnostic image quality was noted in 97.9%
      of 304 coronary segments with median image quality of 3.0. The 300-millisecond
      reconstruction phase provided the highest image quality; 70% of patients showed
      diagnostic image quality. Combination of all phases (250-400 milliseconds)
      performed significantly better than single or other phase combinations (P <
      0.0005 for all comparisons). Inter-reader variability for stenosis detection was
      excellent, with 98.4% concordance by using a binary scale (50% stenosis cutoff).
      CONCLUSIONS: Prospective ECG-triggered sequential dual-source CT acquisition with
      the use of end-systolic acquisition provides diagnostic image quality with
      potentially low radiation doses for evaluation of CAD in patients with AF. Use of
      multiple end-systolic phases over a 150-millisecond window improves diagnostic
      image quality.

PMID- 23545462
TI  - In vitro antimicrobial susceptibility of Brucella melitensis isolates from sheep
      in an area endemic for human brucellosis in Turkey.
AB  - The aim of this study was to assess in vitro antimicrobial susceptibility of
      Brucella melitensis isolates isolated from naturally infected sheep cases in an
      area where human brucellosis is endemic, focusing on rifampin (RIF), streptomycin
      (SM), ciprofloxacin (CPFX), trimethoprim/sulfamethoxazole (TMP/SMZ), gentamicin
      (GM) and tetracycline (TC) and on 11 other antimicrobials. The identification and
      typing of Brucella isolates were carried out using standard classification tests
      and polymerase chain reaction (PCR) methods. Antimicrobial susceptibility testing
      was carried out on Mueller-Hilton agar. The resistance to SM, CPFX and GM was
      determined at the rate of 7.3% and to RIF at the rate of 9.7%. The highest
      (46.3%) resistance was determined against TMP/SMZ. All strains were found to be
      sensitive to TC at the rate of 100.0%. In conclusion, ovine origin B. melitensis
      strains evaluated in this study were resistant to at least one antimicrobial
      (51.2%) that is commonly used in human clinical medicine against brucellosis. 

PMID- 23545463
TI  - Binding analysis of ferritin with heme using alpha-casein and biotinylated-hemin:
      detection of heme-binding capacity of Dpr derived from heme synthesis-deficient
      Streptococcus mutans.
AB  - Bacterial and mammalian ferritins are known to bind heme. The use of alpha-casein
      and biotinylated hemin could be applicable to detection of protein-bound heme and
      of proteins with heme-binding capacity, respectively. Although commercial horse
      spleen ferritin and purified horse spleen ferritin (L:H subunit ratio=4) bound to
      an alpha-casein-coated plate, and this binding could be inhibited by hemin,
      recombinant iron-binding protein (rDpr), derived from heme-deficient
      Streptococcus mutans and expressed in Escherichia coli, did not bind to an alpha
      casein-coated plate. Both horse spleen ferritins bound to alpha-casein
      immobilized beads. Commercial horse spleen ferritin and rDpr showed direct
      binding to hemin-agarose beads. After preincubation of commercial horse spleen
      ferritin or rDpr with biotinylated hemin, they showed indirect binding to avidin
      immobilized beads through biotinylated hemin. These results demonstrate that
      alpha-casein is useful for detection of heme-binding ferritin and that both hemin
      agarose and the combination of biotinylated hemin and avidin-beads are useful for
      detection of the heme-binding capacity of ferritin. In addition, this study also
      revealed that Dpr, a decameric iron-binding protein, from heme-deficient cells
      binds heme. 

PMID- 23545465
TI  - Perceptions and management of psychosocial factors affecting type 2 diabetes
      mellitus in Chinese Americans.
AB  - Diabetes has become a global pandemic and Chinese Americans are at least 60% more
      likely to develop type 2 diabetes than White Americans, despite having lower body
      weight, due to a combination of genetic and environmental factors. Because of the
      increased risk, it is vitally important to address the issues of treatment
      adherence and diabetes self-management in the Chinese American population. Many
      factors affect an individual's ability to manage diabetes, including cultural
      beliefs, immigration experience, language abilities/health literacy, educational
      background, employment, and accessibility of healthcare services. In treating
      Chinese American patients, these factors must be considered to determine
      appropriate treatment. Eastern cultural and individual beliefs differ greatly
      from Western beliefs and, therefore, may affect the presentation of the patients.
      If left unacknowledged, these differences might be misinterpreted by healthcare
      providers as merely treatment non-adherence or unwillingness to change.
      Suggestions for providing culturally competent healthcare are discussed. 

PMID- 23545466
TI  - The psychosocial effects of a companion robot: a randomized controlled trial.
AB  - OBJECTIVES: To investigate the psychosocial effects of the companion robot, Paro,
      in a rest home/hospital setting in comparison to a control group. DESIGN:
      Randomized controlled trial. Residents were randomized to the robot intervention
      group or a control group that attended normal activities instead of Paro
      sessions. Sessions took place twice a week for an hour over 12 weeks. Over the
      trial period, observations were conducted of residents' social behavior when
      interacting as a group with the robot. As a comparison, observations were also
      conducted of all the residents during general activities when the resident dog
      was or was not present. SETTING: A residential care facility in Auckland, New
      Zealand. PARTICIPANTS: Forty residents in hospital and rest home care.
      MEASUREMENTS: Residents completed a baseline measure assessing cognitive status,
      loneliness, depression, and quality of life. At follow-up, residents completed a
      questionnaire assessing loneliness, depression, and quality of life. During
      observations, behavior was noted and collated for instances of talking and
      stroking the dog/robot. RESULTS: In comparison with the control group, residents
      who interacted with the robot had significant decreases in loneliness over the
      period of the trial. Both the resident dog and the seal robot made an impact on
      the social environment in comparison to when neither was present. Residents
      talked to and touched the robot significantly more than the resident dog. A
      greater number of residents were involved in discussion about the robot in
      comparison with the resident dog and conversation about the robot occurred more.
      CONCLUSION: Paro is a positive addition to this environment and has benefits for
      older people in nursing home care. Paro may be able to address some of the unmet
      needs of older people that a resident animal may not, particularly relating to
      loneliness.

PMID- 23545467
TI  - Unraveling the neurobiology of nicotine dependence using genetically engineered
      mice.
AB  - This review article provides an overview of recent studies of nicotine dependence
      and withdrawal that used genetically engineered mice. Major progress has been
      made in recent years with mutant mice that have knockout and gain-of-function of
      specific neuronal nicotinic acetylcholine receptor (nAChR) subunit genes.
      Nicotine exerts its actions by binding to neuronal nAChRs that consist of five
      subunits. The different nAChR subunits that combine to compose a receptor
      determine the distinct pharmacological and kinetic properties of the specific
      nAChR. Recent findings in genetically engineered mice have indicated that while
      alpha4-containing and beta2-containing nAChRs are involved in the acquisition of
      nicotine self-administration and initial stages of nicotine dependence, alpha7
      homomeric nAChRs appear to be involved in the later stages of nicotine
      dependence. In the medial habenula, alpha5-containing, alpha3-containing, and
      beta4-containing nAChRs were shown to be crucially important in the regulation of
      the aversive aspects of nicotine. Studies of the involvement of alpha6 nAChR
      subunits in nicotine dependence have only recently emerged. The use of
      genetically engineered mice continues to vastly improve our understanding of the
      neurobiology of nicotine dependence and withdrawal. 

PMID- 23545468
TI  - Molecular cloning, characterization and expression analysis of a novel wap65-1
      gene from Plecoglossus altivelis.
AB  - Warm temperature acclimation associated 65-kDa protein 1 (WAP65-1) is a specific
      fish plasma glycoprotein that is possibly involved in various physiological or
      pathological processes. In this study, we obtained the cDNA and genomic DNA
      sequences of the Plecoglossus altivelis wap65-1 (Pawap65-1) gene. Multiple
      sequence alignment showed that Pawap65-1 is similar in structure to wap65-1 in
      fish. Phylogenetic analysis revealed that Pawap65-1 is most closely related to
      that of a rainbow trout. Pawap65-1 transcripts are present in various tissues and
      are most abundant in the liver. We expressed recombinant PaWAP65-1 in Escherichia
      coli and raised antiserum against it in mouse. Western blot analysis revealed
      that the higher molecular mass of PaWAP65-1 in blood plasma was caused by post
      translational N-glycosylation. Quantitative real-time quantitative PCR (qPCR) and
      Western blot analysis data showed that the hepatic mRNA and blood plasma levels
      of PaWAP65-1 were both influenced by warm temperature acclimation and cadmium
      exposure, but not by Listonella anguillarum infection, hypo-osmotic, or cold
      temperature acclimation. In conclusion, our data reveals that PaWAP65-1 is a
      stress-related protein, and may play a role in fish acclimation to warm
      temperature and cadmium exposure.

PMID- 23545469
TI  - Seasonal upregulation of catabolic enzymes and fatty acid transporters in the
      flight muscle of migrating hoary bats, Lasiurus cinereus.
AB  - The high energy density of fat, and limited capacity for carbohydrate storage
      suggest that migrating bats should fuel endurance flights with fat, as observed
      in migrating birds. Yet, cursorial mammals are unable to support high intensity
      exercise with fat stores. We hypothesized that migratory bats and birds have
      converged on similar physiological mechanisms to fuel endurance flight with fat.
      We predicted bats would seasonally upregulate fatty acid transport and oxidation
      pathways when migration demands were high. We studied seasonal variation in
      mitochondrial oxidative enzyme activities and fatty acid transport protein
      expression in the flight muscle of hoary bats (Lasiurus cinereus). Carnitine
      palmitoyl transferase, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase
      activity increased during migration. There were no changes in expression of fatty
      acid translocase or plasma membrane fatty acid binding protein. Heart-type fatty
      acid binding protein expression increased 5-fold in migrating females, but did
      not vary seasonally in males. An aerial insectivore lifestyle, and the
      coincidence of migration and pregnancy may explain differences in transporter
      expression compared to previously studied birds. Overall, our results are
      consistent with seasonal upregulation of lipid metabolism and aerobic capacity,
      and confirm that migration poses distinct physiological challenges for bats.

PMID- 23545470
TI  - Recurrent neuromas: a therapeutic challenge?

PMID- 23545471
TI  - Community structure and population dynamics of ammonia oxidizers in composting
      processes of ammonia-rich livestock waste.
AB  - This study investigated the relationship between the population dynamics of
      ammonia-oxidizing bacteria (AOB) and archaea (AOA), and changes in the
      concentrations of nitrogenous compounds during ammonia-rich livestock waste
      composting processes. The data showed that ammonia in beef and dairy cow
      livestock waste-composting piles was slowly oxidized to nitrite and nitrate after
      approximately 21-35 days under thermophilic or moderately thermophilic and
      mesophilic conditions. Real-time quantitative PCR (qPCR) assays showed a relative
      abundance of betaproteobacterial AOB during ammonia oxidation but did not detect
      AOA in any composting stage. Furthermore, real-time qPCR and terminal-restriction
      fragment length polymorphism (T-RFLP) analyses for the AOB in two composting
      processes (beef and dairy cow livestock waste) out of the three studied found
      that thermophilic or moderately thermophilic uncultured betaproteobacterial AOB
      from the "compost AOB cluster" contributed to ammonia oxidation during hot
      composting stages. Non-metric multidimensional scaling analyses of the data from
      T-RFLP showed that only a few analogous species predominated during composting of
      beef, dairy cow and pig livestock wastes, and thus, the AOB community structures
      in the three composting piles operating under different conditions were similar.
      AOB-targeted clone library analyses revealed that uncultured members of the
      "compost AOB cluster", which could be clearly distinguished from the authentic
      species of the genus Nitrosomonas, were the major constituents of the AOB
      populations. These results suggested that a limited and unique species of AOB
      played a role in ammonia oxidation during the composting of ammonia-rich
      livestock waste. 

PMID- 23545472
TI  - Stimulation of the pre-SMA influences cerebral blood flow in frontal areas
      involved with inhibitory control of action.
AB  - Selection of the most appropriate response necessitates inhibition of competing
      or prepotent responses. It is important to characterize which cortical areas are
      relevant to achieve response inhibition. Using the stop signal task, previous
      imaging studies revealed consistent activation in the right pre-supplementary
      motor area (pre-SMA). However, imaging alone suffers from the limitation that it
      can only provide neuronal correlates and cannot establish causality between brain
      activation and behavior. Repetitive transcranial magnetic stimulation (rTMS) can
      be used to temporarily interfere with the function of a cortical area considered
      to play a specific role in the behavior. Thus, we combined rTMS with H(2)(15)O
      positron emission tomography (PET) scans during the stop signal task, to test
      whether rTMS-induced changes in excitability of the right pre-SMA influenced
      response inhibition. We found that rTMS over the pre-SMA increased the efficiency
      of the inhibitory control over prepotent ongoing responses. A significant
      interaction was present in the left inferior frontal gyrus (IFG) along with an
      increase in regional cerebral blood flow (rCBF) in the left pre-SMA, left IFG,
      right premotor and right inferior parietal cortex. These areas best fitted the
      path analysis model in the effective connectivity model. The results of this
      study suggest that stimulation of the right pre-SMA, by interfering with its
      activity, may have a significant impact on response inhibition.

PMID- 23545473
TI  - Impaired motor cortex responses in non-psychotic first-degree relatives of
      schizophrenia patients: a cathodal tDCS pilot study.
AB  - BACKGROUND: Schizophrenia has recently been described as a disorder of impaired
      plasticity and dysconnectivity. Several lines of evidence suggest that
      alterations in glutamatergic neurotransmission underlie different symptom domains
      of schizophrenia. Little is known about the impact of genetic liability on
      cortical plasticity and connectivity in schizophrenia. OBJECTIVE: To compare N
      methyl-d-aspartate receptor (NMDAR)-dependent cortical plasticity and
      connectivity in schizophrenia patients and unaffected first-degree relatives to
      that in healthy subjects. METHODS: Cortical plasticity can be induced in the
      motor cortex with cathodal transcranial direct current stimulation (tDCS). Animal
      and human research indicates that this long-term depression-like plasticity (LTD
      like) is NMDAR dependent, and that these plasticity shifts can last for several
      hours. tDCS-induced plasticity was assessed by measuring motor-evoked potentials
      (MEPs) generated by applying transcranial magnetic stimulation (TMS) to both
      hemispheres in healthy controls, chronically ill schizophrenia patients and
      unaffected first-degree relatives. RESULTS: Compared to healthy controls, both
      first-degree relatives and schizophrenia patients showed abolished motor-cortical
      LTD-like plasticity of the stimulated hemisphere. On the non-stimulated
      hemisphere, plasticity was again abolished in schizophrenia patients, whereas
      first-degree relatives had a reversed plasticity. CONCLUSIONS: Non-psychotic and
      clinically unaffected first-degree relatives showed an alteration and a reversal
      of LTD-like cortical plasticity, indicating functional alterations of
      glutamatergic transmission as a result of a genetic liability for developing
      schizophrenia. These results provide new evidence for the association between
      plasticity dysregulation and functional cortical connectivity, and the importance
      of these networks in the pathophysiology of schizophrenia.

PMID- 23545475
TI  - [Ramadan and bipolar disorder: Example of circadian rhythm disturbance and its
      impact on patients with bipolar disorders].
AB  - INTRODUCTION: Fasting during the Ramadan month is a cornerstone of Islam. Several
      disorders of the chronobiological rhythms occur during this month and impact on
      mood. Through this paper the authors provide a literature review of the impact of
      fasting on patients with bipolar disorders. MATERIALS AND SUBJECTS: A literature
      review using Mesh keywords through Medline database. From 1970 to 2011, articles
      in French and English were selected. RESULTS: Circadian rhythm refers to the
      approximately 24-hour cycles that are generated by an organism. Most
      physiological systems demonstrate circadian variations. Many hormones and other
      metabolisms, such as gastric pH, insulin, glucose, calcium and plasmatic
      gastrine, have been shown to exhibit circadian oscillation. The role of social
      rhythm in behaviors and its influence on circadian rhythms in humans is now
      obvious. It has been shown that the lack of concentration and irritability
      increased continuously during Ramadan month and reached its peak at the end of
      the month. Mood and vigilance are significantly decreased during the fasting
      month. Several authors have stated that the course of bipolar illness may be
      affected by the changes in social rhythm that occur during Ramadan (fasting
      month). Studies which have been devoted to this topic are sparse. Kadri et al.,
      in 2000, studied 20 bipolar patients during the fasting month of Ramadan of 1417
      (Hegirian calendar, corresponding to January 1997). Diagnosis of bipolar disorder
      was made according to ICD-10 criteria. Patients were assessed during the week
      before Ramadan, the second and the fourth weeks of the fasting month and the
      first week after its end, with the Hamilton Depression and Bech-Rafaelsen scales.
      The plasma concentration of lithium was also assessed. The main finding of the
      study was that 45% of the patients relapsed, 70% during the second week, and the
      remaining patients at the end of Ramadan. These relapses were not related to
      plasma concentration of lithium. Most of the relapses were manic (71,4%).
      Patients who did not relapse had more insomnia and anxiety during the second and
      third weeks of the study. The side effects of lithium increased and were seen in
      48% of the sample, mostly dryness of the mouth with thirst and tremor. However,
      Farooq et al. in 2006 studied 62 bipolar patients during the fasting month of
      Ramadan 1427 (from 25 September to 24 October 2006). Serum lithium, electrolytes,
      Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were
      assessed, one week before Ramadan, mid Ramadan and one week after Ramadan. The
      side effects and toxicity were measured by symptoms and signs checklist. There
      was no significant difference in mean serum lithium levels at three time points.
      The scores on HDRS and YMRS showed significant decrease during Ramadan (F=34,12,
      P=0,00, for HDRS and F=15,6, P=0,000 for YMRS). Also the side effects and
      toxicity did not differ significantly at the three point's assessment.
      CONCLUSION: All physiologic parameters are influenced by the circadian rhythm,
      which is influenced in its turn by the food rhythm. So far, the results of these
      two main studies, with opposite results, do not help us advise bipolar patients
      to fast or not to fast. Other studies in this field are badly needed.

PMID- 23545476
TI  - [Nanopsychiatry. The potential role of nanotechnologies in the future of
      psychiatry. A systematic review].
AB  - INTRODUCTION: Nanomedicine is defined as the area using nanotechnology's concepts
      for the benefit of human beings, their health and well being. The field of
      nanotechnology opened new unsuspected fields of research a few years ago. AIM OF
      THE STUDY: To provide an overview of nanotechnology application areas that could
      affect care for psychiatric illnesses. METHODS: We conducted a systematic review
      using the PRISMA criteria (preferred reporting items for systematic reviews and
      meta-analysis). Inclusion criteria were specified in advance: all studies
      describing the development of nanotechnology in psychiatry. The research paradigm
      was: "(nanotechnology OR nanoparticles OR nanomedicine) AND (central nervous
      system)" Articles were identified in three research bases, Medline (1966
      present), Web of Science (1975-present) and Cochrane (all articles). The last
      search was carried out on April 2, 2012. Seventy-six items were included in this
      qualitative review. RESULTS: The main applications of nanotechnology in
      psychiatry are (i) pharmacology. There are two main difficulties in
      neuropharmacology. Drugs have to pass the blood brain barrier and then to be
      internalized by targeted cells. Nanoparticles could increase drugs'
      bioavailability and pharmacokinetics, especially improving safety and efficacy of
      psychotropic drugs. Liposomes, nanosomes, nanoparticle polymers, nanobubbles are
      some examples of this targeted drug delivery. Nanotechnologies could also add new
      pharmacological properties, like nanohells and dendrimers; (ii) living analysis.
      Nanotechnology provides technical assistance to in vivo imaging or metabolome
      analysis; (iii) central nervous system modeling. Research teams have modelized
      inorganic synapses and mimicked synaptic behavior, essential for further creation
      of artificial neural systems. Some nanoparticle assemblies present the same small
      world and free-scale network architecture as cortical neural networks.
      Nanotechnologies and quantum physics could be used to create models of artificial
      intelligence and mental illnesses. DISCUSSION: Even if nanotechnologies are
      promising, their safety is still tricky and this must be kept in mind.
      CONCLUSION: We are not about to see a concrete application of nanomedicine in
      daily psychiatric practice. However, it seems essential that psychiatrists do not
      forsake this area of research the perspectives of which could be decisive in the
      field of mental illness.

PMID- 23545477
TI  - [Self-esteem and giftedness: a Rorschach Comprehensive System study].
AB  - BACKGROUND: According to empirical literature, low self-esteem is highly
      correlated to behavioural and emotional problems in gifted children and
      adolescents. Since self-esteem is an indicator of social and emotional
      adjustment, it would be interesting to better understand the meaning of this
      construct, as it is evaluated explicitly with the use of self-report
      questionnaires. In order to explore the psychological processes underlying the
      explicit self-esteem, we studied the relation of a self-report questionnaire and
      an indirect measure of self and interpersonal perception using the Rorschach
      Comprehensive System (CS). METHOD: The participants were 93 children, aged
      between 9 and 15 years old, with an IQ>=130. They were attending regular classes
      (no curriculum difference). Self-esteem was evaluated using the Coopersmith Self
      Esteem Inventory (SEI). We used the Rorschach CS measures of self and
      interpersonal perception. RESULTS: The results showed no significant correlation
      between self-esteem and high IQ. A negative correlation between self-esteem
      evaluated on the SEI and the Rorschach Vista responses was found, which reflected
      self-critical introspection and painful self-appraisal. Then a positive
      correlation was observed between self-esteem and reflection answers on the
      Rorschach (Fr+rF>0), which are related to narcissistic-like features of
      personality. We also found a positive correlation between self-esteem and the
      Rorschach egocentricity index (EGO), which provides an estimate of self-concern.
      Finally, the strongest correlation was found between self-esteem and the
      dominance of good over poor human representations (GHR>PHR), which reveals
      effective interpersonal behaviour. DISCUSSION: The psychological processes which
      seem to be related to low self-esteem in gifted children and adolescents are
      maladaptive interpersonal behaviours, painful experience of introspection
      focusing on perceived negative aspects of the self, absence of narcissistic-like
      features of the personality and low self-concern. These findings may suggest that
      intervention planning with gifted children and adolescents with low self-esteem
      should emphasize the accurate interpretation of interpersonal data, develop
      social skills and restructure negative self-thoughts.

PMID- 23545478
TI  - Novel mouse model of chronic inflammatory and overactive bladder by a single
      intravesical injection of hydrogen peroxide.
AB  - There is so far no generally accepted animal model of chronic cystitis by which
      potential therapies can be evaluated. In this study, we aimed to establish a new
      mouse model of cystitis based on the proinflammatory effects of reactive oxygen
      species. A single intravesical injection of 1.5% hydrogen peroxide (H2O2)
      significantly increased the numbers of voids by 1 day after injection in female
      mice, which lasted up to 7 days. The H2O2 injection rapidly increased the bladder
      weight by 3 h in parallel with the histological damage and hyperpermeability of
      urothelial barrier. Although the urothelial dysfunction was recovered to normal
      by 7 days, increase in bladder weight, edematous thickening of the submucosa, and
      vascular hyperpermeability were apparent even 7 days after injection. During the
      time course, massive infiltration of neutrophils and increased expression of
      inflammatory cytokines were observed in the bladder. An intraperitoneal
      administration of oxybutynin, amitriptyline, indomethacin, or morphine attenuated
      the H2O2-induced frequent urination. These findings suggest that an intravesical
      injection of H2O2 induces relatively long-lasting inflammatory and overactive
      bladder, compared with existing cystitis models. The intravesical H2O2 injection
      model may be a simple and useful tool in the pathological study and drug
      discovery for chronic cystitis.

PMID- 23545479
TI  - Effects of Helicobacter pylori infection on gastric parietal cells and E-cadherin
      in Mongolian gerbils.
AB  - Atrophic gastritis caused by infection with Helicobacter pylori is characterized
      by parietal cell loss, which is a main risk factor for gastric cancer. Parietal
      cells play a crucial role in the regulation of cell lineage maturation and
      proliferation in the gastric units. Among the classical cadherins, E-cadherin
      plays an important role not only in epithelial cell-cell connections, but also in
      the maintenance of epithelial polarity and gastric glandular architecture and
      regulation of cell proliferation. The aim of this study is to elucidate how
      parietal cells and E-cadherin are altered in gastritis with Helicobacter pylori
      infection. We studied the effects of Helicobacter pylori on gastric mucosal E
      cadherin 2 weeks after inoculation and investigated the relationship between
      parietal cell loss and the amount of E-cadherin on parietal cells in Mongolian
      gerbils. The number of parietal cells and amount of staining of E-cadherin below
      the isthmus were investigated by immunohistochemistry. It was shown that a
      reduction in intercellular E-cadherin preceded the disappearance of parietal
      cells. The gastric glands where parietal cells were lost were replaced by mucus
      secreting cells without E-cadherin. These results suggest that Helicobacter
      pylori damaged E-cadherin on parietal cells and caused massive parietal cell
      loss, leading to the deregulation of gastric morphology.

PMID- 23545480
TI  - Vaccination of goats with DNA vaccine encoding Dim-1 induced partial protection
      against Haemonchus contortus: a preliminary experimental study.
AB  - Disorganized muscle family member (Dim-1) belongs to immunoglobulin superfamily,
      and is a structural protein localized to the region of the muscle cell membrane
      around and between the dense bodies. Strong immunogenicity to host's immune
      system was induced by Dim-1 from Ascaris suum, which indicated that Dim-1 could
      be a potential candidate for vaccine. The homologues of Dim-1 were also detected
      in nematodes Brugia malayi and Trichostrongylus colubriformis. However,
      information on the complete coding sequence and protection potential of this
      molecule in Haemonchus contortus is lacking. In this study, full length of Dim-1
      cDNA was cloned using a rapid amplification of cDNA ends (RACE) strategy and the
      DNA vaccine encoding Dim-1 open reading frame (ORF) was tested for protection
      against experimental H. contortus infections in goats. Fifteen goats were
      allocated into three trial groups. The animals of Dim-1 group were vaccinated
      with the DNA vaccine encoding Dim-1 on day 0 and 14, and challenged with 5000
      infective H. contortus third larval stage (L3) on day 28. An unvaccinated
      positive control group was challenged with L3 at the same time. An unvaccinated
      negative control group was not challenged with L3. The results indicated Dim-1
      DNA vaccines were transcribed at local injection sites and expressed in vivo post
      immunizations respectively. Following L3 challenge, the mean eggs per gram feces
      (EPG) and worm burdens of Dim-1 group were reduced by 45.7% and 51.1%,
      respectively. Significantly high levels of serum IgG, serum IgA, mucosal IgA,
      CD4(+) T lymphocytes and B lymphocytes of Dim-1 group were produced. While
      compared with the negative control group, increased numbers of blood eosinophils
      and lymphocytes and declined haemoglobin level were observed in the Dim-1 group
      after L3 challenge. The preliminary study suggest that recombinant H. contortus
      Dim-1 DNA vaccine induced partial immune response and has protective potential
      against goat haemonchosis.

PMID- 23545482
TI  - Does respiratory sinus arrhythmia (RSA) predict anxiety reduction during
      cognitive behavioral therapy (CBT) for social anxiety disorder (SAD)?
AB  - Modifying dysfunctional emotion regulation is an important goal in psychological
      treatments for social anxiety disorder (SAD). Antecedent-focused strategies
      learned in cognitive behavioral therapy (CBT), such as cognitive reappraisal,
      have proven more effective in reducing social anxiety than response-focused
      strategies, such as expressive suppression. Still, not all patients with SAD
      respond well to CBT. Medications and physiological factors may also influence the
      clinical response. The purpose of the present study was to examine the role that
      these factors play in determining treatment response following CBT for SAD. Using
      multilevel modeling, we examined associations across four separate laboratory
      visits between change in self-reported anxiety and indices of reappraisal,
      suppression, medication status, and resting respiratory sinus arrhythmia (RSA), a
      proxy measure of self-regulatory capacity, in 23 socially anxious adults during a
      12-week program of CBT. Most participants were ultimately classified as
      responders to CBT (n=15), but in some, anxiety levels remained unchanged (n=8).
      Medication use explained substantial variance related to individual differences
      in anxiety among participants. When modeled separately, reappraisal, suppression,
      and RSA each accounted for significant variance related to anxiety. However, the
      best-fitting model included reappraisal and RSA. Moreover, RSA reactivity (change
      in RSA levels over time) was more important for predicting anxiety reduction than
      were baseline levels of RSA. These findings suggest that reappraisal and
      parasympathetic responsiveness may be important in reducing anxiety in adults
      with SAD who respond well to CBT.

PMID- 23545481
TI  - In vitro intestinal and hepatic metabolism of Di(2-ethylhexyl) phthalate (DEHP)
      in human and rat.
AB  - Species and organ differences in the intrinsic clearance and the enzymes involved
      in the metabolism of DEHP were examined in subcellular fractions of the intestine
      and liver as well as by recombinant cytochrome P450 (CYP) isoforms of human and
      rat. Estimated clearance (CLint) of DEHP via esterase-mediated pathway in human
      intestine was 2.4-fold greater than that in human liver while its value in rat
      intestine was 1.7-fold less than that in rat liver. Ranks of CLint for CYP
      mediated oxidation/dealkylation of MEHP were human liver>rat liver>human
      intestine>rat intestine. Estimates of CLint for the production of mono(2-ethyl-5
      hydroxyhexyl) phthalate and mono(2-ethyl-5-oxohexyl) phthalate by human CYP2C9 1
      were 4.2- and 2.6-fold greater than those by rat CYP2C6, respectively. Total
      CLint via hCYP2C9 3-mediated oxidation was 1.9- and 2.6-fold less than those by
      hCYP2C9 2 and 2C9 1, respectively. Estimated CLint for phthalic acid production
      by hCYP3A4 was 24.5 MUL nmol CYP(-1)min(-1) while it was continuously produced by
      rCYP2C6 and 3A2 via passive mechanism. These species/organ differences in major
      metabolic pathway and CYP isoforms should be considered for appraisal of the
      potential adverse health effects of DEHP.

PMID- 23545483
TI  - Putting all your eggs in one basket: life-history strategies, bet hedging, and
      diversification.
AB  - Diversification of resources is a strategy found everywhere from the level of
      microorganisms to that of giant Wall Street investment firms. We examine the
      functional nature of diversification using life-history theory-a framework for
      understanding how organisms navigate resource-allocation trade-offs. This
      framework suggests that diversification may be adaptive or maladaptive depending
      on one's life-history strategy and that these differences should be observed
      under conditions of threat. In three studies, we found that cues of mortality
      threat interact with one index of life-history strategy, childhood socioeconomic
      status (SES), to affect diversification. Among those from low-SES backgrounds,
      mortality threat increased preferences for diversification. However, among those
      from high-SES backgrounds, mortality threat had the opposite effect, inclining
      people to put all their eggs in one basket. The same interaction pattern emerged
      with a potential biomarker of life-history strategy, oxidative stress. These
      findings highlight when, and for whom, different diversification strategies can
      be advantageous.

PMID- 23545474
TI  - Chemosignals, hormones and mammalian reproduction.
AB  - Many mammalian species use chemosignals to coordinate reproduction by altering
      the physiology and behavior of both sexes. Chemosignals prime reproductive
      physiology so that individuals become sexually mature and active at times when
      mating is most probable and suppress it when it is not. Once in reproductive
      condition, odors produced and deposited by both males and females are used to
      find and select individuals for mating. The production, dissemination and
      appropriate responses to these cues are modulated heavily by organizational and
      activational effects of gonadal sex steroids and thereby intrinsically link
      chemical communication to the broader reproductive context. Many compounds have
      been identified as "pheromones" but very few have met the expectations of that
      term: a unitary, species-typical substance that is both necessary and sufficient
      for an experience-independent behavioral or physiological response. In contrast,
      most responses to chemosignals are dependent or heavily modulated by experience,
      either in adulthood or during development. Mechanistically, chemosignals are
      perceived by both main and accessory (vomeronasal) olfactory systems with the
      importance of each system tied strongly to the nature of the stimulus rather than
      to the response. In the central nervous system, the vast majority of responses to
      chemosignals are mediated by cortical and medial amygdala connections with
      hypothalamic and other forebrain structures. Despite the importance of
      chemosignals in mammals, many details of chemical communication differ even among
      closely related species and defy clear categorization. Although generating much
      research and public interest, strong evidence for the existence of a robust
      chemical communication among humans is lacking.

PMID- 23545484
TI  - Responses of male sperm whales (Physeter macrocephalus) to killer whale sounds:
      implications for anti-predator strategies.
AB  - Interactions between individuals of different cetacean species are often observed
      in the wild. Killer whales (Orcinus orca) can be potential predators of many
      other cetaceans, and the interception of their vocalizations by unintended
      cetacean receivers may trigger anti-predator behavior that could mediate predator
      prey interactions. We explored the anti-predator behaviour of five typically
      solitary male sperm whales (Physeter macrocephalus) in the Norwegian Sea by
      playing sounds of mammal-feeding killer whales and monitoring behavioural
      responses using multi-sensor tags. Our results suggest that, rather than taking
      advantage of their large aerobic capacities to dive away from the perceived
      predator, sperm whales responded to killer whale playbacks by interrupting their
      foraging or resting dives and returning to the surface, changing their vocal
      production, and initiating a surprising degree of social behaviour in these
      mostly solitary animals. Thus, the interception of predator vocalizations by male
      sperm whales disrupted functional behaviours and mediated previously unrecognized
      anti-predator responses.

PMID- 23545485
TI  - Obesity: Behavioural weight-loss intervention in high-risk patients.

PMID- 23545486
TI  - Adrenal function: Cortisol metabolism during acute stress--an (IC)U turn.

PMID- 23545487
TI  - Maternal vitamin D status--not the key to offspring bone health?

PMID- 23545488
TI  - Metabolism: Contribution of B cells to obesity and insulin resistance.

PMID- 23545489
TI  - Characterisation of the ecotoxicity of hospital effluents: a review.
AB  - The multiple activities that take place in hospitals (surgery, drug treatments,
      radiology, cleaning of premises and linen, chemical and biological analysis
      laboratories, etc.), are a major source of pollutant emissions into the
      environment (disinfectants, detergents, drug residues, etc.). Most of these
      pollutants can be found in hospital effluents (HWW), then in urban sewer networks
      and WWTP (weakly adapted for their treatment) and finally in aquatic
      environments. In view to evaluating the impact of these pollutants on aquatic
      ecosystems, it is necessary to characterise their ecotoxicity. Several reviews
      have focused on the quantitative and qualitative characterisation of pollutants
      present in HWW. However, none have focused specifically on the characterisation
      of their experimental ecotoxicity. We have evaluated this according to two
      complementary approaches: (i) a "substance" approach based on the identification
      of the experimental data in the literature for different substances found in
      hospital effluents, and on the calculation of their PNEC (Predicted Non Effect
      Concentration), (ii) a "matrix" approach for which we have synthesised
      ecotoxicity data obtained from the hospital effluents directly. This work first
      highlights the diversity of the substances present within hospital effluents, and
      the very high ecotoxicity of some of them (minimum PNEC observed close to 0,01
      pg/L). We also observed that the consumption of drugs in hospitals was a
      predominant factor chosen by authors to prioritise the compounds to be sought.
      Other criteria such as biodegradability, excretion rate and the bioaccumulability
      of pollutants are considered, though more rarely. Studies of the ecotoxicity of
      the particulate phase of effluents must also be taken into account. It is also
      necessary to monitor the effluents of each of the specialised departments of the
      hospital studied. These steps is necessary to define realistic environmental
      management policies for hospitals (replacement of toxic products by less
      pollutant ones, etc.).

PMID- 23545490
TI  - Maternal Steller sea lion diets elevate fetal mercury concentrations in an area
      of population decline.
AB  - Total mercury concentrations ([THg]) measured in western Aleutian Island Steller
      sea lion pup hair were the highest maximum [THg] documented in this endangered
      species to date. Some pups exceeded concentrations at which other fish-eating
      mammals can exhibit adverse neurological and reproductive effects (21% and 15%
      pups above 20 and 30 MUg/g in hair, respectively). Of particular concern is fetal
      exposure to mercury during a particularly vulnerable stage of neurological
      development in late gestation. Hair and blood [THg] were highly correlated and
      20% of pups sampled in the western Aleutian Islands of Alaska exceeded mammalian
      risk thresholds established for each of these tissues. Higher nitrogen isotope
      ratios suggested that pups accumulated the highest [THg] when their dams fed on
      higher trophic level prey during late gestation.

PMID- 23545491
TI  - Debates, dialectic, and rhetoric: an approach to teaching radiology residents
      health economics, policy, and advocacy.
AB  - Arguing is an art and essential to the functioning of our political and legal
      system. Moderated debates between residents are a useful educational vehicle to
      teach residents health economics and health policy. Articulating the opposing
      arguments leads to greater mutual understanding, an appreciation of the limits of
      knowledge and improved advocacy.

PMID- 23545492
TI  - Genomic aspects of NAFLD pathogenesis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most predominant liver disease
      worldwide and hepatic manifestation of the metabolic syndrome. Its histology
      spectrum ranges from steatosis, to steatohepatitis (NASH) that can further
      progress to cirrhosis and hepatocellular carcinoma (HCC). The increasing
      incidence of NAFLD has contributed to rising numbers of HCC occurrences. NAFLD
      progression is governed by genetic susceptibility, environmental factors,
      lifestyle and features of the metabolic syndrome, many of which overlap with HCC.
      Gene expression profiling and genome wide association studies have identified
      novel disease pathways and polymorphisms in genes that may be potential
      biomarkers of NAFLD progression. However, the multifactorial nature of NAFLD and
      the limited number of sufficiently powered studies are among the current
      limitations for validated biomarkers of clinical utility. Further studies
      incorporating the links between circadian regulation and hepatic metabolism might
      represent an additional direction in the search for predictive biomarkers of
      liver disease progression and treatment outcomes. 

PMID- 23545493
TI  - Describing intrinsically disordered proteins at atomic resolution by NMR.
AB  - There is growing interest in the development of physical methods to study the
      conformational behaviour and biological activity of intrinsically disordered
      proteins (IDPs). In this review recent advances in the elucidation of
      quantitative descriptions of disordered proteins from nuclear magnetic resonance
      spectroscopy are presented. Ensemble approaches are particularly well adapted to
      map the conformational energy landscape sampled by the protein at atomic
      resolution. Significant advances in development of calibrated approaches to the
      statistical representation of the conformational behaviour of IDPs are presented,
      as well as applications to some biologically important systems where disorder
      plays a crucial role.

PMID- 23545494
TI  - Preventing adsorption of immunoglobulin G to solid surfaces using poloxamer 407
      eliminates artifactual stimulation of neutrophils.
AB  - To study the effect of polyclonal intravenous immunoglobulin G (IVIG) on
      neutrophils in vitro, adsorption of immunoglobulin G (IgG) to solid surfaces has
      to be prevented, because IgG bound to a solid surface can activate neutrophils
      through activating FcgammaRs. In this study we demonstrate that poloxamer 407, a
      non ionic surfactant, at low concentration (0.05%) prevented the adsorption of
      high concentrations of IgG (5 mg/ml) better than other blocking agents without
      interfering with the interaction of IgG with the neutrophils. Poloxamer 407 is
      therefore a suitable blocking agent to prevent the interaction of immunoglobulin
      with solid surfaces in cell-based in vitro experiments.

PMID- 23545495
TI  - A proteomic characterization of factors enriched at nascent DNA molecules.
AB  - DNA replication is facilitated by multiple factors that concentrate in the
      vicinity of replication forks. Here, we developed an approach that combines the
      isolation of proteins on nascent DNA chains with mass spectrometry (iPOND-MS),
      allowing a comprehensive proteomic characterization of the human replisome and
      replisome-associated factors. In addition to known replisome components, we
      provide a broad list of proteins that reside in the vicinity of the replisome,
      some of which were not previously associated with replication. For instance, our
      data support a link between DNA replication and the Williams-Beuren syndrome and
      identify ZNF24 as a replication factor. In addition, we reveal that SUMOylation
      is widespread for factors that concentrate near replisomes, which contrasts with
      lower UQylation levels at these sites. This resource provides a panoramic view of
      the proteins that concentrate in the surroundings of the replisome, which should
      facilitate future investigations on DNA replication and genome maintenance.

PMID- 23545496
TI  - ER stress causes rapid loss of intestinal epithelial stemness through activation
      of the unfolded protein response.
AB  - Stem cells generate rapidly dividing transit-amplifying cells that have lost the
      capacity for self-renewal but cycle for a number of times until they exit the
      cell cycle and undergo terminal differentiation. We know very little of the type
      of signals that trigger the earliest steps of stem cell differentiation and
      mediate a stem cell to transit-amplifying cell transition. We show that in normal
      intestinal epithelium, endoplasmic reticulum (ER) stress and activity of the
      unfolded protein response (UPR) are induced at the transition from stem cell to
      transit-amplifying cell. Induction of ER stress causes loss of stemness in a Perk
      eIF2alpha-dependent manner. Inhibition of Perk-eIF2alpha signaling results in
      stem cell accumulation in organoid culture of primary intestinal epithelium. Our
      findings show that the UPR plays an important role in the regulation of
      intestinal epithelial stem cell differentiation.

PMID- 23545497
TI  - UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by
      targeting MAVS.
AB  - RNA viruses are sensed by RIG-I-like receptors (RLRs), which signal through a
      mitochondria-associated adaptor molecule, MAVS, resulting in systemic antiviral
      immune responses. Although RLR signaling is essential for limiting RNA virus
      replication, it must be stringently controlled to prevent damage from
      inflammation. We demonstrate here that among all tested UBX-domain-containing
      protein family members, UBXN1 exhibits the strongest inhibitory effect on RNA
      virus-induced type I interferon response. UBXN1 potently inhibits RLR- and MAVS
      induced, but not TLR3-, TLR4-, or DNA-virus-induced innate immune responses.
      Depletion of UBXN1 enhances virus-induced innate immune responses, including
      those resulting from RNA viruses such as vesicular stomatitis, Sendai, West Nile,
      and dengue virus infection, repressing viral replication. Following viral
      infection, UBXN1 is induced, binds to MAVS, interferes with intracellular MAVS
      oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. These findings
      underscore a critical role of UBXN1 in the modulation of a major antiviral
      signaling pathway.

PMID- 23545498
TI  - C/EBPalpha induces highly efficient macrophage transdifferentiation of B lymphoma
      and leukemia cell lines and impairs their tumorigenicity.
AB  - Earlier work demonstrated that the transcription factor C/EBPalpha can convert
      immature and mature murine B lineage cells into functional macrophages. Testing
      >20 human lymphoma and leukemia B cell lines, we found that most can be
      transdifferentiated at least partially into macrophage-like cells, provided that
      C/EBPalpha is expressed at sufficiently high levels. A tamoxifen-inducible
      subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPalphaER, could
      be efficiently converted into phagocytic and quiescent cells with a transcriptome
      resembling normal macrophages. The converted cells retained their phenotype even
      when C/EBPalpha was inactivated, a hallmark of cell reprogramming. Interestingly,
      C/EBPalpha induction also impaired the cells' tumorigenicity. Likewise,
      C/EBPalpha efficiently converted a lymphoblastic leukemia B cell line into
      macrophage-like cells, again dramatically impairing their tumorigenicity. Our
      experiments show that human cancer cells can be induced by C/EBPalpha to
      transdifferentiate into seemingly normal cells at high frequencies and provide a
      proof of principle for a potential new therapeutic strategy for treating B cell
      malignancies.

PMID- 23545499
TI  - The SH2 domain interaction landscape.
AB  - Members of the SH2 domain family modulate signal transduction by binding to short
      peptides containing phosphorylated tyrosines. Each domain displays a distinct
      preference for the sequence context of the phosphorylated residue. We have
      developed a high-density peptide chip technology that allows for probing of the
      affinity of most SH2 domains for a large fraction of the entire complement of
      tyrosine phosphopeptides in the human proteome. Using this technique, we have
      experimentally identified thousands of putative SH2-peptide interactions for more
      than 70 different SH2 domains. By integrating this rich data set with orthogonal
      context-specific information, we have assembled an SH2-mediated probabilistic
      interaction network, which we make available as a community resource in the
      PepspotDB database. A predicted dynamic interaction between the SH2 domains of
      the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the
      extracellular signal-regulated kinase activation loop was validated by
      experiments in living cells.

PMID- 23545500
TI  - Macrohistone variants preserve cell identity by preventing the gain of H3K4me2
      during reprogramming to pluripotency.
AB  - Transcription-factor-induced reprogramming of somatic cells to pluripotency is a
      very inefficient process, probably due to the existence of important epigenetic
      barriers that are imposed during differentiation and that contribute to
      preserving cell identity. In an effort to decipher the molecular nature of these
      barriers, we followed a genome-wide approach, in which we identified macrohistone
      variants (macroH2A) as highly expressed in human somatic cells but downregulated
      after reprogramming to pluripotency, as well as strongly induced during
      differentiation. Knockdown of macrohistone variants in human keratinocytes
      increased the efficiency of reprogramming to pluripotency, whereas overexpression
      had opposite effects. Genome-wide occupancy profiles show that in human
      keratinocytes, macroH2A.1 preferentially occupies genes that are expressed at low
      levels and are marked with H3K27me3, including pluripotency-related genes and
      bivalent developmental regulators. The presence of macroH2A.1 at these genes
      prevents the regain of H3K4me2 during reprogramming, imposing an additional layer
      of repression that preserves cell identity.

PMID- 23545501
TI  - Mechanism of origin DNA recognition and assembly of an initiator-helicase complex
      by SV40 large tumor antigen.
AB  - The DNA tumor virus Simian virus 40 (SV40) is a model system for studying
      eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase
      that is essential for genome replication. LTag recognizes and assembles at the
      viral replication origin. We determined the structure of two multidomain LTag
      subunits bound to origin DNA. The structure reveals that the origin binding
      domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and
      assembly. Notably, the OBDs recognize the origin in an unexpected manner. The
      histidine residues of the AAA+ domains insert into a narrow minor groove region
      with enhanced negative electrostatic potential. Computational analysis indicates
      that this region is intrinsically narrow, demonstrating the role of DNA shape
      readout in origin recognition. Our results provide important insights into the
      assembly of the LTag initiator/helicase at the replication origin and suggest
      that histidine contacts with the minor groove serve as a mechanism of DNA shape
      readout.

PMID- 23545502
TI  - Balancing of histone H3K4 methylation states by the Kdm5c/SMCX histone
      demethylase modulates promoter and enhancer function.
AB  - The functional organization of eukaryotic genomes correlates with specific
      patterns of histone methylations. Regulatory regions in genomes such as enhancers
      and promoters differ in their extent of methylation of histone H3 at lysine-4
      (H3K4), but it is largely unknown how the different methylation states are
      specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the
      Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter
      elements in mouse embryonic stem cells and in neuronal progenitor cells.
      Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our
      data indicate that by restricting H3K4me3 modification at core promoters, Kdm5c
      dampens transcription, but at enhancers Kdm5c stimulates their activity.
      Remarkably, an impaired enhancer function activates the intrinsic promoter
      activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c
      demethylase plays a crucial and dynamic role in the functional discrimination
      between enhancers and core promoters.

PMID- 23545503
TI  - Robust on-line sampling and analysis during long-term perfusion cultivation of
      mammalian cells.
AB  - In an attempt to support robust automated sampling and analysis of mammalian cell
      bioreactors, an integrated platform, BaychroMA(r), was developed which includes
      an innovative sterile sampling device, automated sample transport, a sample
      preparation module, online analyzers, and communication interfaces to process
      automation systems. The robustness of this platform was verified by applying it
      to a laboratory-scale perfusion bioreactor that was operated for over 100 days.
      Both manual and automated samples were collected over the course of the run and a
      comparison was made for cell density, viability, glucose, and lactate
      concentrations. The highest variability (14.4%) was seen for cell density
      estimates while those for viability, glucose, and lactate were 0.7, 12.9, and
      8.2%, respectively. In addition, cell density set-point changes were made towards
      the end of the perfusion culture and the high frequency automated samples
      provided a higher resolution description of the dynamics of cell density change
      compared to less frequent manual sampling. Overall, our results indicate stable
      and robust operation of the BaychroMAT(r) platform in a long-term perfusion
      culture. This success should readily translate to shorter duration fed-batch
      cultures thereby enabling feed-back control based on real-time nutrient
      measurements.

PMID- 23545504
TI  - Penetration of nanoparticles in flax (Linum usitatissimum L.) calli and
      regenerants.
AB  - We demonstrate a method for direct delivery of metal nanoparticles to flax calli
      and regenerant cells by vacuum deposition of metal nanolayers on powdered hormone
      followed by dispersal of the combined hormone-metal in medium. The penetration
      and location of the gold (AuNPs) and silver (AgNPs) nanoparticles in calli and in
      plant regenerants were confirmed by optical absorption spectroscopy and scanning
      electron microscopy. We detected a significant effect of the AuNPs and AgNPs on
      the regeneration type of flax calli.

PMID- 23545505
TI  - Novel sphingosine-1-phosphate receptor modulator KRP203 combined with locally
      delivered regulatory T cells induces permanent acceptance of pancreatic islet
      allografts.
AB  - BACKGROUND: KRP203, a structural FTY720 analogue, has 5-fold greater selectivity
      for binding to sphingosine-1-phosphate receptor (S1PR) 1 (S1PR(1)) versus S1PR3
      and 100-fold greater selectivity over S1PR(2) and S1PR(5). Although the
      immunoregulatory effects of FTY720 have been tested in clinical and experimental
      research, the therapeutic efficacy of KRP203 in allograft models remains elusive.
      In this study, we investigated the potential of KRP203 alone and in combination
      with intragraft injection of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) to
      induce islet allograft tolerance. METHODS: BALB/c (H-2(d)) mice received
      transplants of fresh C57BL/10 (H-2(b)) islet allografts under the kidney capsule
      and were treated for 7 days with 0.3, 1.0, or 3.0 mg/kg KRP203 alone or in
      combination with intragraft-infused Tregs. RESULTS: Untreated BALB/c mice acutely
      rejected C57BL/10 islet allografts at a mean survival time of 13.8 +/- 2.7 days
      (n=5). A 7-day dosing of 0.3 or 1.0 mg/kg KRP203 produced long-term islet
      allograft survival (9200 days) in one of five and two of seven recipients,
      respectively. A 3 mg/kg KRP203 dose resulted in islet graft survival for more
      than 200 days in 5 of 12 recipients. Whereas recipients that received 500
      allogeneic islets admixed with 5 x 10(5) - 7 x 10(5) Tregssurvived 83.6 +/- 67.2
      days, addition of transient 3 mg/kg KRP203 therapy induced prolonged drug-free
      graft survival (9200 days) in all recipients. CONCLUSIONS: A brief treatment with
      KRP203 significantly prolonged islet allograft survival, whereas additional
      intragraft delivery of Tregs induced tolerogenic effects selective to islet
      alloantigens.

PMID- 23545506
TI  - Screening for BK viremia reduces but does not eliminate the risk of BK
      nephropathy: a single-center retrospective analysis.
AB  - BACKGROUND: This study reviewed the outcomes of a screening protocol for BK
      viremia to determine if early diagnosis, followed by immunosuppression
      minimization, would prevent progression to nephropathy and graft loss. METHODS:
      This review included 369 renal transplant recipients tested for BK virus at
      serial time points after transplantation. Management included immunosuppression
      minimization plus cidofovir treatment for BK nephropathy. RESULTS: Recipients
      received tacrolimus-based immunosuppression, with 8% prednisone-free and 6% who
      received desensitization. With a mean follow-up of 22 +/- 10 months, 16% (n = 57)
      of recipients became BK viremia positive. The median (range) time to diagnosis
      was 3 (1-17) months. Because renal biopsy was performed selectively, 59% of
      recipients underwent biopsy, with 47% showing BK nephropathy. Seventy-four
      percent of recipients cleared the virus at a median (range) time of 9 (3-33)
      months, with four grafts lost to BK nephropathy. Cidofovir-treated recipients
      displayed a higher viral load at diagnosis but showed equivalent renal function
      at last evaluation. In multivariate analysis, recipient age, Asian ethnicity,
      deceased donor, and prednisone use were factors independently associated with BK
      viremia. Actuarial survival of BK-positive grafts was worse than that of BK
      negative grafts (P<0.01, log-rank test). At 9 and 12 months, the mean estimated
      glomerular filtration rate of the BK-positive group was lower than that of the BK
      negative cohort (P = 0.02). CONCLUSIONS: Despite using a screening protocol
      combined with immunosuppression minimization, BK-positive recipients had a
      greater risk of graft loss and impaired function than recipients free of
      infection. Future investigations should focus on practices to prevent BK viremia.

PMID- 23545507
TI  - Prevention of de novo hepatitis B in recipients of core antibody-positive livers
      with lamivudine and other nucleos(t)ides: a 12-year experience.
AB  - BACKGROUND: Lamivudine (LAM) has been shown to prevent de novo hepatitis B virus
      (HBV) infection in recipients of hepatitis B core antibody (HBcAb)-positive liver
      transplants (LT) but primarily in small studies with limited follow-up. METHODS:
      We conducted a retrospective cohort study of HBcAb+ graft recipients at our
      institution from October 1999 to August 2008. RESULTS: One hundred nineteen
      recipients without prior HBV were identified (median age, 54 years; 70% male), of
      which 62 received LAM. The median follow-up was 2.6 years overall and 5.3 years
      in the LAM group. Among LAM recipients, 44% were HBV naive (HBsAb-/HBcAb-) at LT,
      of which 6% developed HBsAb+ and 3% developed HBcAb+ after LT. Eight percent
      developed de novo HBV: two recipients became hepatitis B surface antigen positive
      at 70 and 23 months and three experienced breakthrough with HBV DNA more than
      2000 IU at 1 to 9 months after LT. Sixty percent (3 of 5) were HBV naive. Four
      (6%) other recipients also had transiently detectable HBV less than 2000 IU,
      which did not require any changes to their prophylaxis regimen. When compared
      with recipients who received other nucleos(t)ide analogues, there was no
      difference in de novo rates: LAM 8% (5 of 62), adefovir 15% (5 of 33), tenofovir
      0% (0 of 3), entecavir 0% (0 of 1), and 5% (1 of 20) for those not given
      prophylaxis (P=0.59). CONCLUSIONS: LAM monoprophylaxis was effective in
      preventing de novo HBV in the vast majority of recipients over long-term follow
      up. Adefovir had a higher rate of de novo infections numerically, whereas
      tenofovir and entecavir had no cases and may be more effective, but this was
      limited by a small sample size.

PMID- 23545508
TI  - Management of the brain-dead organ donor: a systematic review and meta-analysis.
AB  - BACKGROUND: The shortage of organs is a limitation for transplantation, making
      the care of potential organ donors an important issue. The present systematic
      review and meta-analysis was carried out to assess the efficacy of interventions
      to stabilize hemodynamics in brain-dead donors or to improve organ function and
      outcomes of transplantation. METHODS: Medline, Embase, and Cochrane databases
      were searched. Of 5096 articles retrieved, 39 randomized controlled trials were
      selected. Twenty were included in a qualitative synthesis, providing data on 1277
      patients. The main interventions described were desmopressin use,
      triiodothyronine and methylprednisolone replacement, fluid management,
      vasopressor therapy, mechanical ventilation strategies, and surgical techniques.
      RESULTS: Three meta-analyses were conducted: the first included two studies and
      showed that desmopressin administered to brain-dead patients was not advantageous
      with respect to early organ function in kidney recipients (relative risk, 0.97;
      95% confidence interval [CI], 0.85-1.10; I(2) = 0%; P = 0.809). The second
      included four studies and showed that triiodothyronine did not add hemodynamic
      benefits versus standard management (weighted mean difference, 0.15; 95% CI, 
      0.13 to 0.42; I(2) = 17.4%; P = 0.304). The third meta-analysis (two studies)
      showed that ischemic liver preconditioning during harvesting procedures did not
      benefit survival (relative risk, 1.0; 95% CI, 0.93-1.08; I(2) = 0%; P = 0.459).
      CONCLUSION: The present results suggest limited efficacy of interventions
      focusing on the management of brain-dead donors.

PMID- 23545509
TI  - Outcomes in systemic sclerosis-related lung disease after lung transplantation.
AB  - BACKGROUND: Lung disease is the leading cause of death in systemic sclerosis
      (SSc). The diagnosis of SSc-related lung disease (SSc-LD) is often a
      contraindication to lung transplantation (LT) due to concerns that extrapulmonary
      involvement will yield worse outcomes. We sought to evaluate posttransplantation
      outcomes in persons with SSc-LD with esophageal involvement compared with persons
      with nonconnective tissue disease-related interstitial lung disease (nCTD-ILD).
      METHODS: From 1998 to 2012, persons undergoing LT for SSc-LD were age and gender
      matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal
      function was assessed by pH testing and manometry. We defined esophageal
      dysfunction as the presence of a DeMeester score >14 or dysmotility more severe
      than "mild nonspecific disorder". The primary outcome was posttransplantation
      survival. Secondary outcomes included freedom from bronchiolitis obliterans
      syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated
      with Kaplan-Meier methods. Acute rejection was compared with Student's t test.
      RESULTS: Survival was similar in 23 persons with SSc-LD and 46 controls who
      underwent LT (P = 0.47). For the SSc-LD group, 1- and 5-year survival was 83% and
      76% compared with 91% and 64% in the nCTD-ILD group, respectively. There were no
      differences in fBOS (P = 0.83). Rates of acute rejection were less in SSc-ILD (P
      = 0.05). Esophageal dysfunction was not associated with worse outcomes (P>0.55).
      CONCLUSIONS: Persons with SSc-LD appear to have similar survival and fBOS as
      persons transplanted for nCTD-ILD. The risk of acute rejection after
      transplantation may be reduced in persons with SSc-LD. Esophageal involvement
      does not appear to impact outcomes.

PMID- 23545510
TI  - Postliver transplantation pulmonary complications: is modified clinical pulmonary
      infection score applicable?

PMID- 23545511
TI  - Postliver transplantation pulmonary complications: is modified clinical pulmonary
      infection score applicable?

PMID- 23545512
TI  - Decreased donation: experience and further concern from developing countries.

PMID- 23545513
TI  - Transcranial sonography as a bridge to brain death diagnosis.

PMID- 23545514
TI  - The effect of donor kidney volume on recipient outcomes: "dose" matters.

PMID- 23545515
TI  - Organ donation and Rendu-Osler-Weber syndrome.

PMID- 23545516
TI  - Successful repair of kidney graft artery rupture using external stenting.

PMID- 23545517
TI  - Effects of oral paricalcitol on secondary hyperparathyroidism and proteinuria of
      kidney transplant patients.

PMID- 23545518
TI  - Actopaxin has a role in HCC metastasis.

PMID- 23545519
TI  - Sofosbuvir: a new milestone in HCV treatment?

PMID- 23545520
TI  - Novel pathway identified for glutamine metabolism in PDAC.

PMID- 23545521
TI  - Elderly-onset IBD: a milder disease?
AB  - Patients with elderly-onset IBD are more likely to have marked comorbidities and
      polypharmacy than those diagnosed at a younger age, which might affect
      therapeutic decision-making. Increased knowledge of this higher-risk group might
      guide patient management. Data from a large population-based study evaluating the
      clinical presentation and course of elderly-onset IBD are discussed.

PMID- 23545522
TI  - Childhood gastroenteritis--the rise of norovirus.

PMID- 23545524
TI  - Human organic cation transporters 1 (SLC22A1), 2 (SLC22A2), and 3 (SLC22A3) as
      disposition pathways for fluoroquinolone antimicrobials.
AB  - Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against
      a wide range of bacterial pathogens and excellent tissue permeation. They exist
      as charged molecules in biological fluids, and thus, their disposition depends
      heavily on active transport and facilitative diffusion. A recent review of the
      clinical literature indicated that tubular secretion and reabsorption are major
      determinants of their half-life in plasma, efficacy, and drug-drug interactions.
      In particular, reported in vivo interactions between FQs and cationic drugs
      affecting renal clearance implicated organic cation transporters (OCTs). In this
      study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin,
      lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin,
      rufloxacin, and sparfloxacin, were screened for their ability to inhibit
      transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3
      (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1
      mediated uptake under initial test conditions. None of the FQs inhibited hOCT2,
      and only moxifloxacin inhibited hOCT3 (~30%), even at a 1,000-fold excess.
      Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be
      competitive inhibitors of hOCT1. Inhibition constants (K(i)) were estimated to be
      250 +/- 18 MUM, 161 +/- 19 MUM, 136 +/- 33 MUM, and 94 +/- 8 MUM, respectively.
      Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a K(i) value of
      1,598 +/- 146 MUM. Despite expression in enterocytes (luminal), hepatocytes
      (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to
      contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal
      membrane of hepatocytes, and potentially the basolateral membrane of proximal
      tubule cells, is likely to play a role in the disposition of these antimicrobial
      agents.

PMID- 23545525
TI  - Pharmacokinetics of daptomycin in a patient with severe renal failure not
      receiving dialysis.

PMID- 23545523
TI  - Management of varices in patients with cirrhosis.
AB  - Variceal bleeding remains a life-threatening condition with a 6-week mortality
      rate of ~20%. Prevention of variceal bleeding can be achieved using nonselective
      beta-blockers (NSBBs) or endoscopic band ligation (EBL), with NSBBs as the first
      line treatment. EBL should be reserved for cases of intolerance or
      contraindications to NSBBs. Although NSBBs cannot be used to prevent varices, if
      the hepatic venous pressure gradient (HVPG) is <=10 mmHg, prognosis is excellent.
      Survival after acute variceal bleeding has improved over the past three decades,
      but patients with Child-Pugh grade C cirrhosis remain at greatest risk.
      Vasoactive drugs combined with endoscopic therapy and antibiotics are the best
      therapeutic strategy for these patients. Transjugular intrahepatic portosystemic
      shunts (TIPS) should be used in patients with uncontrolled bleeding or those who
      are likely to have difficult-to-control bleeding. Rebleeding from varices occurs
      in ~60% of patients 1-2 years after the initial bleeding episode, with a
      mortality rate of 30%. Secondary prophylaxis should start at day 6 after initial
      bleeding using a combination of NSBBs and EBL. TIPS with polytetrafluoroethylene
      covered stents are the preferred option in patients who fail combined treatment
      with NSBBs and EBL. Despite the improvement in patient survival, further studies
      are needed to direct the management of patients with gastro-oesophageal varices
      and variceal bleeding. 

PMID- 23545526
TI  - Emergence of extensively drug-resistant Haemophilus parainfluenzae in
      Switzerland.
AB  - Two homosexual men were colonized in the urethra with Haemophilus parainfluenzae
      nonsusceptible to ampicillin (MIC, 8 MUg/ml), amoxicillin-clavulanate (MIC, 4
      MUg/ml), cefotaxime (MIC, 1.5 MUg/ml), cefepime (MIC, 3 MUg/ml), meropenem (MIC,
      0.5 MUg/ml), cefuroxime, azithromycin, ciprofloxacin, tetracycline, and
      chloramphenicol (all MICs, >= 32 MUg/ml). Repetitive extragenic palindromic PCR
      (rep-PCR) showed that the strains were indistinguishable. The isolates had amino
      acid substitutions in PBP3, L4, GyrA, and ParC and possessed Mef(A), Tet(M), and
      CatS resistance mechanisms. This is the first report of extensively drug
      resistant (XDR) H. parainfluenzae.

PMID- 23545527
TI  - Comparative activities of telavancin combined with nafcillin, imipenem, and
      gentamicin against Staphylococcus aureus.
AB  - Beta-lactams enhance the killing activity of vancomycin. Due to structural and
      mechanistic similarities between vancomycin and telavancin, we investigated the
      activity of telavancin combined with nafcillin and imipenem compared to the known
      synergistic combination of telavancin and gentamicin. Thirty strains of
      Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10
      methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin
      intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology.
      Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in
      vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10
      mg/kg of body weight of telavancin once daily alone and combined with 2 g
      nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily
      over 72 h. In the synergy test, 67% of strains displayed synergy with the
      combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and
      63% with telavancin and imipenem. In the PK/PD model, the activities of all three
      combinations against MRSA and hVISA were superior to all individual drugs alone
      (P <= 0.002) and were similar to each other (P >= 0.187). The activities of all
      three combinations against MSSA were generally similar to each other except for
      one strain where the combination of telavancin and imipenem was superior to all
      other regimens (P <= 0.011). The activity of the combination of telavancin and
      beta-lactam agents was similar to that of telavancin and gentamicin against S.
      aureus, including resistant strains. Because beta-lactam combinations are less
      likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam
      combinations may have clinical utility.

PMID- 23545528
TI  - Use of rifamycin drugs and development of infection by rifamycin-resistant
      strains of Clostridium difficile.
AB  - The relationship between rifamycin drug use and the development of resistant
      strains of Clostridium difficile was studied at a large university hospital in
      Houston, TX, between May 2007 and September 2011. In 49 of 283 (17.3%) patients
      with C. difficile infection (CDI), a rifamycin-resistant strain of C. difficile
      was identified that compares to a rate of 8% using the same definitions in 2006
      2007 (P = 0.59). The 49 patients infected by a resistant organism were matched by
      date of admission to 98 control patients with CDI from whom a rifamycin
      susceptible C. difficile strain was isolated. Cases and controls did not differ
      according to demographic and clinical characteristics and showed similar but low
      rates of prior rifamycin use. Similar rates of rifamycin resistance were seen in
      cases of hospital-acquired CDI (38/112 [34%]) versus community-acquired CDI (7/20
      [35%]). At a university hospital in which rifaximin was commonly used, infection
      by rifamycin-resistant strains of C. difficile was not shown to relate to prior
      use of a rifamycin drug or to acquiring the infection in the hospital, although
      the rate of overall resistance appeared to be rising.

PMID- 23545529
TI  - Safety and tolerability of luliconazole solution 10-percent in patients with
      moderate to severe distal subungual onychomycosis.
AB  - The study objective was to evaluate the safety, tolerability, systemic exposure,
      and pharmacokinetics (PK) of 10% luliconazole solution (luliconazole) when
      topically applied once daily to all 10 toenails and periungual areas in patients
      with moderate to severe distal subungual onychomycosis. In this single-center,
      open-label study, 24 patients applied 20 mg/ml of luliconazole (twice the
      clinical dose) for 29 days with a 7-day follow-up. Complete PK profiles were
      determined on days 1, 8, 15, and 29. Safety/tolerability assessments included
      application site reactions, adverse events, vital signs, clinical laboratory
      findings, and electrocardiograms. Mean luliconazole plasma concentrations
      remained around the lower limit of quantitation (0.05 ng/ml) and were comparable
      on days 8, 15, and 29 (range, 0.063 to 0.090 ng/ml), suggesting steady state
      occurred by day 8. Every patient had undetectable plasma luliconazole levels for
      at least 11% of the time points, and 12 of the 24 patients had undetectable
      levels for at least 70% of the time points. The maximum plasma concentration of
      luliconazole (C(max)) observed in any patient was 0.314 ng/ml and the maximum
      area under the concentration-time curve from 0 to 24 h (AUC0-24) was 4.34 ng .
      h/ml. Five patients (21%) had measureable luliconazole levels in the plasma 7
      days after the last dose. The median concentration of luliconazole in the nail at
      this time point was 34.65 mg/g (from 42 of 48 collected toenail samples). There
      was one mild incidence of skin erythema on day 5 that resolved on day 8, there
      were no reports of drug-induced systemic side effects, and there was no evidence
      of QT prolongation. Luliconazole, when applied once daily to all 10 fungus
      infected toenails for 29 days, is generally safe and well tolerated and results
      in significant accumulation of drug in the nail. Systemic exposure is very low,
      with no evidence of drug accumulation.

PMID- 23545530
TI  - Kinetic and structural analysis for potent antifolate inhibition of Pneumocystis
      jirovecii, Pneumocystis carinii, and human dihydrofolate reductases and their
      active-site variants.
AB  - A major concern of immunocompromised patients, in particular those with AIDS, is
      susceptibility to infection caused by opportunistic pathogens such as
      Pneumocystis jirovecii, which is a leading cause of pneumonia in
      immunocompromised patients. We report the first kinetic and structural data for
      2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine (OAAG324),
      a potent inhibitor of dihydrofolate reductase (DHFR) from P. jirovecii (pjDHFR),
      and also for trimethoprim (TMP) and methotrexate (MTX) with pjDHFR, Pneumocystis
      carinii DHFR (pcDHFR), and human DHFR (hDHFR). OAAG324 shows a 9.0-fold
      selectivity for pjDHFR (Ki, 2.7 nM) compared to its selectivity for hDHFR (Ki,
      24.4 nM), whereas there is only a 2.3-fold selectivity for pcDHFR (Ki, 6.3 nM).
      In order to understand the determinants of inhibitory potency, active-site
      mutations of pj-, pc-, and hDHFR were explored to make these enzymes more like
      each other. The most unexpected observations were that the variant pcDHFR forms
      with K37Q and K37Q/F69N mutations, which made the enzyme more like the human
      form, also made these enzymes more sensitive to the inhibitory activity of
      OAAG324, with Ki values of 0.26 and 0.71 nM, respectively. A similar gain in
      sensitivity was also observed for the hDHFR N64F variant, which showed a lower Ki
      value (0.58 nM) than native hDHFR, pcDHFR, or pjDHFR. Structural data are
      reported for complexes of OAAG324 with hDHFR and its Q35K and Q35S/N64F variants
      and for the complex of the K37S/F69N variant of pcDHFR with TMP. These results
      provide useful insight into the role of these residues in the optimization of
      highly selective inhibitors of DHFR against the opportunistic pathogen P.
      jirovecii.

PMID- 23545532
TI  - The apparent quorum-sensing inhibitory activity of pyrogallol is a side effect of
      peroxide production.
AB  - There currently is more and more interest in the use of natural products, such as
      tea polyphenols, as therapeutic agents. The polyphenol compound pyrogallol has
      been reported before to inhibit quorum-sensing-regulated bioluminescence in
      Vibrio harveyi. Here, we report that the addition of 10 mg . liter(-1) pyrogallol
      protects both brine shrimp (Artemia franciscana) and giant river prawn
      (Macrobrachium rosenbergii) larvae from pathogenic Vibrio harveyi, whereas the
      compound showed relatively low toxicity (therapeutic index of 10). We further
      demonstrate that the apparent quorum-sensing-disrupting activity is a side effect
      of the peroxide-producing activity of this compound rather than true quorum
      sensing inhibition. Our results emphasize that verification of minor toxic
      effects by using sensitive methods and the use of appropriate controls are
      essential when characterizing compounds as being able to disrupt quorum sensing.

PMID- 23545531
TI  - Identification and characterization of a novel HIV-1 nucleotide-competing reverse
      transcriptase inhibitor series.
AB  - Several groups have recently reported on the identification of nucleotide
      competing reverse transcriptase inhibitors (NcRTIs), a new class of RT
      inhibitors. NcRTIs reversibly inhibit binding of the incoming nucleotide to the
      RT active site but do not act as chain terminators, unlike the nucleos(t)ide
      reverse transcriptase inhibitor (NRTI) class. We identified a novel
      benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI chemical series. Structure-activity
      relationship evaluation of this series with both RT and viral replication assays
      led to the identification of compound A, a new NcRTI. Compound A inhibited HIV-1
      RT in a primer extension assay (50% inhibitory concentration, 2.6 nM) but had no
      measurable activity against human DNA polymerase gamma at 10 MUM. It potently
      inhibited HIV-1 replication in vitro (50% effective concentration, 1.5 nM). The
      antiviral potency of compound A was unaffected by the presence of nonnucleotide
      RT inhibitor (NNRTI) mutations tested (L100I, K103N/Y181C, V106A, or Y188L).
      Notably, viruses encoding K65R were hypersusceptible to inhibition by compound A.
      Compound A also retained full activity against viruses encoding M184V. In vitro
      selection for resistant virus to compound A led to the selection of a single
      substitution within RT: W153L. A recombinant virus encoding the RT W153L was
      highly resistant to compound A (fold change, 160). W153 is a highly conserved
      residue in HIV RT and has not been previously associated with drug resistance. In
      summary, a novel NcRTI series with optimized antiviral activity, minimal cross
      resistance to existing RT inhibitor classes, and a distinct resistance profile
      has been discovered. These results further establish NcRTIs as an emerging class
      of antiretroviral agents.

PMID- 23545533
TI  - Evaluation of ceftaroline activity against heteroresistant vancomycin
      intermediate Staphylococcus aureus and vancomycin-intermediate methicillin
      resistant S. aureus strains in an in vitro pharmacokinetic/pharmacodynamic model:
      exploring the "seesaw effect".
AB  - A "seesaw effect" in methicillin-resistant Staphylococcus aureus (MRSA) has been
      demonstrated, whereby susceptibility to beta-lactam antimicrobials increases as
      glyco- and lipopeptide susceptibility decreases. We investigated this effect by
      evaluating the activity of the anti-MRSA cephalosporin ceftaroline against
      isogenic pairs of MRSA strains with various susceptibilities to vancomycin in an
      in vitro pharmacokinetic/pharmacodynamic (PK/PD) model. The activities of
      ceftaroline at 600 mg every 12 h (q12h) (targeted free maximum concentration of
      drug in serum [fC(max)], 15.2 MUg/ml; half-life [t(1/2)], 2.3 h) and vancomycin
      at 1 g q12h (targeted fC(max), 18 MUg/ml; t(1/2), 6 h) were evaluated against 3
      pairs of isogenic clinical strains of MRSA that developed increased MICs to
      vancomycin in patients while on therapy using a two-compartment hollow-fiber
      PK/PD model with a starting inoculum of ~10(7) CFU/ml over a 96-h period.
      Bacterial killing and development of resistance were evaluated. Expression of
      penicillin-binding proteins (PBPs) 2 and 4 was evaluated by reverse transcription
      (RT)-PCR. The achieved pharmacokinetic parameters were 98 to 119% of the targeted
      values. Ceftaroline and vancomycin were bactericidal against 5/6 and 1/6 strains,
      respectively, at 96 h. Ceftaroline was more active against the mutant strains
      than the parent strains, with this difference being statistically significant for
      2/3 strain pairs at 96 h. The level of PBP2 expression was 4.4* higher in the
      vancomycin-intermediate S. aureus (VISA) strain in 1/3 pairs. The levels of PBP2
      and PBP4 expression were otherwise similar between the parent and mutant strains.
      These data support the seesaw hypothesis that ceftaroline, like traditional beta
      lactams, is more active against strains that are less susceptible to vancomycin
      even when the ceftaroline MICs are identical. Further research to explore these
      unique findings is warranted.

PMID- 23545534
TI  - Efficacy and safety of liposomal clarithromycin and its effect on Pseudomonas
      aeruginosa virulence factors.
AB  - We investigated the efficacy and safety of liposomal clarithromycin formulations
      with different surface charges against clinical isolates of Pseudomonas
      aeruginosa from the lungs of cystic fibrosis (CF) patients. The liposomal
      clarithromycin formulations were prepared by the dehydration-rehydration method,
      and their sizes were measured using the dynamic-light-scattering technique.
      Encapsulation efficiency was determined by microbiological assay, and the
      stabilities of the formulations in biological fluid were evaluated for a period
      of 48 h. The MICs and minimum bactericidal concentrations (MBCs) of free and
      liposomal formulations were determined with P. aeruginosa strains isolated from
      CF patients. Liposomal clarithromycin activity against biofilm-forming P.
      aeruginosa was compared to that of free antibiotic using the Calgary Biofilm
      Device (CBD). The effects of subinhibitory concentrations of free and liposomal
      clarithromycin on bacterial virulence factors and motility on agar were
      investigated on clinical isolates of P. aeruginosa. The cytotoxicities of the
      liposome preparations and free drug were evaluated on a pulmonary epithelial cell
      line (A549). The average diameter of the formulations was >222 nm, with
      encapsulation efficiencies ranging from 5.7% to 30.4%. The liposomes retained
      more than 70% of their drug content during the 48-h time period. The highly
      resistant strains of P. aeruginosa became susceptible to liposome-encapsulated
      clarithromycin (MIC, 256 mg/liter versus 8 mg/liter; P < 0.001). Liposomal
      clarithromycin reduced the bacterial growth within the biofilm by 3 to 4 log
      units (P < 0.001), significantly attenuated virulence factor production, and
      reduced bacterial twitching, swarming, and swimming motilities. The
      clarithromycin-entrapped liposomes were less cytotoxic than the free drug (P <
      0.001). These data indicate that our novel formulations could be a useful
      strategy to enhance the efficacy of clarithromycin against resistant P.
      aeruginosa strains that commonly affect individuals with cystic fibrosis.

PMID- 23545536
TI  - Assessment of the genotoxicity and antigenotoxicity of (+)-usnic acid in V79
      cells and Swiss mice by the micronucleus and comet assays.
AB  - Usnic acid is one of the most common and abundant metabolites found in various
      lichen genera, which are important sources of biologically active compounds. The
      aim of this study was to evaluate the genotoxic and antigenotoxic potential of
      (+)-usnic acid (UA) by the micronucleus and comet assays in V79 cell cultures and
      Swiss mice. For assessment of genotoxicity, V79 cells were treated with 15, 30,
      60, and 120MUg/mL UA, established based on clonogenic efficiency cytotoxic assay.
      Swiss mice were treated with UA doses of 25, 50, 100, and 200mg/kg body weight.
      The same concentrations of UA were combined with methyl methanesulfonate (MMS)
      for evaluation of antigenotoxicity. The in vitro results demonstrated that UA
      induced DNA damage at concentrations of 60 and 120MUg/mL in the comet assay.
      However, no genotoxic effect was observed in the micronucleus test using V79
      cells at the concentrations tested. No genotoxic effects were observed for the
      different UA treatments in in vivo test system. Combined administration of UA and
      MMS significantly reduced the frequencies of micronuclei and DNA damage in vitro
      and in vivo when compared to treatment with MMS alone. Although the mechanisms
      underlying the protective effect of UA are not completely understood, the
      antioxidant activity of this metabolite may explain its protective effect against
      MMS-induced genotoxicity.

PMID- 23545537
TI  - Laser directed lithography of asymmetric graphene ribbons on a
      polydimethylsiloxane trench structure.
AB  - Recently, manipulating heat transport by asymmetric graphene ribbons has received
      significant attention, in which phonons in the carbon lattice are used to carry
      energy. In addition to heat control, asymmetric graphene ribbons might also have
      broad applications in renewable energy engineering, such as thermoelectric energy
      harvesting. Here, we transfer a single sheet of graphene over a 5 MUm trench of
      polydimethylsiloxane (PDMS) structure. By using a laser (1.77 mW, 1 MUm diameter
      spot size, 517 nm wavelength) focusing on one side of the suspended graphene, a
      triangular shaped graphene ribbon is obtained. As the graphene has a negative
      thermal expansion coefficient, local laser heating could make the affected
      graphene area shrink and eventually break. Theoretical calculation shows that the
      1.77 mW laser could create a local hot spot as high as 1462.5  degrees C, which
      could induce an asymmetric shape structure. We also find the temperature
      coefficient (-13.06 cm(-1) mW) of suspended graphene on PDMS trench substrate is
      ten times higher than that reported on SiO2/Si trench substrate. Collectively,
      our results raise the exciting prospect that the realization of graphene with
      asymmetric shape on thermally insulating substrate is technologically feasible,
      which may open up important applications in thermal circuits and thermal
      management.

PMID- 23545535
TI  - Anthracene-polyamine conjugates inhibit in vitro proliferation of
      intraerythrocytic Plasmodium falciparum parasites.
AB  - Anthracene-polyamine conjugates inhibit the in vitro proliferation of the
      intraerythrocytic human malaria parasite Plasmodium falciparum, with 50%
      inhibitory concentrations (IC50s) in the nM to MUM range. The compounds are taken
      up into the intraerythrocytic parasite, where they arrest the parasite cell
      cycle. Both the anthracene and polyamine components of the conjugates play a role
      in their antiplasmodial effect.

PMID- 23545538
TI  - Contractivity of a Markov operator on the space of normalised positive
      distributions.
AB  - The goal of the article is to establish the contractivity, on the space of
      normalised positive distributions, of a certain class of Markov operators defined
      by stochastic kernels. The motivation for this work is the promising use of
      stationary densities in characterising convergence properties of a certain class
      of discrete-time random algorithms, especially when the so-called associated
      ordinary differential equation has multiple asymptotically stable equilibria, and
      no other stable structures.

PMID- 23545539
TI  - Adaptive training of cortical feature maps for a robot sensorimotor controller.
AB  - This work investigates self-organising cortical feature maps (SOFMs) based upon
      the Kohonen Self-Organising Map (SOM) but implemented with spiking neural
      networks. In future work, the feature maps are intended as the basis for a
      sensorimotor controller for an autonomous humanoid robot. Traditional SOM methods
      require some modifications to be useful for autonomous robotic applications.
      Ideally the map training process should be self-regulating and not require
      predefined training files or the usual SOM parameter reduction schedules. It
      would also be desirable if the organised map had some flexibility to accommodate
      new information whilst preserving previous learnt patterns. Here methods are
      described which have been used to develop a cortical motor map training system
      which goes some way towards addressing these issues. The work is presented under
      the general term 'Adaptive Plasticity' and the main contribution is the
      development of a 'plasticity resource' (PR) which is modelled as a global
      parameter which expresses the rate of map development and is related directly to
      learning on the afferent (input) connections. The PR is used to control map
      training in place of a traditional learning rate parameter. In conjunction with
      the PR, random generation of inputs from a set of exemplar patterns is used
      rather than predefined datasets and enables maps to be trained without deciding
      in advance how much data is required. An added benefit of the PR is that, unlike
      a traditional learning rate, it can increase as well as decrease in response to
      the demands of the input and so allows the map to accommodate new information
      when the inputs are changed during training.

PMID- 23545540
TI  - The power of connectivity: identity preserving transformations on visual streams
      in the spike domain.
AB  - We investigate neural architectures for identity preserving transformations
      (IPTs) on visual stimuli in the spike domain. The stimuli are encoded with a
      population of spiking neurons; the resulting spikes are processed and finally
      decoded. A number of IPTs are demonstrated including faithful stimulus recovery,
      as well as simple transformations on the original visual stimulus such as
      translations, rotations and zoomings. We show that if the set of receptive fields
      satisfies certain symmetry properties, then IPTs can easily be realized and
      additionally, the same basic stimulus decoding algorithm can be employed to
      recover the transformed input stimulus. Using group theoretic methods we advance
      two different neural encoding architectures and discuss the realization of exact
      and approximate IPTs. These are realized in the spike domain processing block by
      a "switching matrix" that regulates the input/output connectivity between the
      stimulus encoding and decoding blocks. For example, for a particular connectivity
      setting of the switching matrix, the original stimulus is faithfully recovered.
      For other settings, translations, rotations and dilations (or combinations of
      these operations) of the original video stream are obtained. We evaluate our
      theoretical derivations through extensive simulations on natural video scenes,
      and discuss implications of our results on the problem of invariant object
      recognition in the spike domain.

PMID- 23545541
TI  - Highly sensitive fluorescent protein FRET detection using optofluidic lasers.
AB  - We achieved optofluidic protein lasing using genetically encoded fluorescent
      protein FRET pairs linked by length-tunable peptides. Up to 25-fold reduction in
      the donor laser emission was observed when the donor and the acceptor were
      brought to close proximity, as compared to only 17% reduction in the donor
      emission using the conventional FRET detection. Our work opens a door to a broad
      range of applications in studying protein-protein interactions and protein-drug
      interactions.

PMID- 23545542
TI  - Sevoflurane, but not propofol, reduces the lung inflammatory response and
      improves oxygenation in an acute respiratory distress syndrome model: a
      randomised laboratory study.
AB  - CONTEXT: Acute respiratory distress syndrome is characterised by activation of
      the inflammatory cascade. The only treatment that reduces the mortality rate
      associated with this syndrome is lung protective ventilation, which requires
      sedation of patients. Sedation in critical care units is usually induced
      intravenously, although there is reason to believe that inhaled anaesthetics are
      a suitable alternative. Sevoflurane has recently been shown to modulate the lung
      inflammatory response in a model of lung injury more favourably than propofol.
      OBJECTIVE: The goal of this study was to confirm whether or not sevoflurane is
      more effective than propofol in ameliorating the inflammatory response in an
      animal model of acute respiratory distress syndrome. DESIGN: A prospective,
      randomised, controlled study. SETTING: Research foundation laboratory at the
      Hospital Clinico Universitario, Valencia, Spain. EXPERIMENTAL ANIMALS: Sixteen
      Landrace/large white crossbred pigs weighing 30 to 45 kg. INTERVENTIONS: Animals
      were allocated randomly to one of two groups: one sedated with intravenous
      propofol 5 to 7 mg kg h (group P) and the other with sevoflurane, administered
      using an AnaConDa device to obtain an end-tidal concentration of 1.5% (group S).
      Monitoring, lung protective ventilation and anaesthetic management were identical
      in both groups. MAIN OUTCOME MEASURES: The PaO2/FiO2 ratio and cytokine
      concentrations in bronchoalveolar lavage specimens were determined at 10, 150 and
      240 min after confirmation of acute respiratory distress syndrome (PaO2/FiO2
      <26.7 kPa). RESULTS: At 240 min, median and interquartile range (IQR)
      concentrations of cytokines in bronchial lavage specimens in group S were lower
      than those in group P [interleukin-1beta (IL-1beta) 53, IQR 16-140 vs. 311, IQR
      183-637 pg ml, P = 0.04; tumour necrosis factor-alpha 347, IQR 161-433 vs. 552,
      IQR 475-649 pg ml, P = 0.04; and IL-6 101, IQR 76-282 vs. 580, IQR 369-701 pg ml,
      P = 0.03]. The polymorphonuclear neutrophil count was also lower in group S (P =
      0.007), which also had a higher PaO2/FiO2 ratio. TRIAL REGISTRATION: GE-015/09.
      CONCLUSION: In an animal model of acute respiratory distress syndrome,
      sevoflurane ameliorates the lung inflammatory response and improves oxygenation
      to a greater extent than propofol.

PMID- 23545543
TI  - Evidence for different patterns of natural inter-genotype recombination between
      two PCV2 parental strains in the field.
AB  - Co-infection with different virus strains is a precondition for genome
      recombination, which give rise to continuous evolution of porcine circovirus type
      2 (PCV2). In the present study, 32 PCV2 positive clinical samples from the
      diseased and dead pigs were identified by classic PCR. 15 of 32 (46.8%) clinical
      samples were identified as infection with both PCV2a and PCV2b using genotype
      specific PCR. 13/15 of PCV2 strains were identified as recombinants using
      sequencing analysis, phylogenetic analysis, recombination detection program and
      base-by-base comparison. Further analyses of the full-length sequences of these
      strains suggest that the natural recombination events occurred between strains
      DQ104423 (PCV2a) and AY579893 (PCV2b), yield two new recombinant clusters through
      different recombination patterns with crossover regions located in ORF2.
      Recombinant cluster 1 included 3 strains, and recombinant cluster 2 included 10
      strains. These results demonstrate that recombination between PCV2a and PCV2b
      strains can occur in cap protein coding region through different patterns and
      yield different recombinants. Our study not only provided new evidences that PCV2
      strains can undergo recombination through a variety of patterns, but also
      suggests that recombination events easily occur in the co-existence of different
      strains of PCV2.

PMID- 23545544
TI  - Within-host competition between barley yellow dwarf-PAV and -PAS.
AB  - The PAV and PAS species of barley yellow dwarf virus (Luteoviridae) share hosts,
      vectors, and have sympatric distributions. To better understand how competition
      between species influences virus growth within the host, transmission rate
      between hosts, and ultimately virus population structure two experiments were
      conducted. The first experiment varied the order of PAV and PAS inoculation and
      the time interval between the first and second inoculation. Relative virus
      concentration was measured at 8, 20, 33, and 45 days after primary virus
      inoculation (dpi). Regardless of the order of inoculation or the length of time
      between inoculations, PAV dominated the virus population by 33 dpi (PAV
      concentration ranged from 55% to 89%). The second experiment measured the rate of
      vector transmission from single and multiple infections. From single infections,
      the transmission rate was 67% for PAV and 60% for PAS. PAV had significantly
      greater odds of transmission for all competition treatments-except if PAS was
      given a 15-day head start before inoculation with PAV. In the latter treatment,
      PAS was transmitted with a greater frequency than PAV, but the difference was not
      statistically significant. Our data show persistent co-infection between PAV and
      PAS, but PAV is more likely to be transmitted from mixed infections. Thus, within
      host interactions between PAV and PAS create conditions that promote both the
      competitive exclusion of PAS, as well as co-existence between species and the
      maintenance of genetic diversity in the host community.

PMID- 23545546
TI  - Exploring the role of the buddy scheme for researchers.

PMID- 23545547
TI  - A child with high fever: Kawasaki disease.
AB  - Kawasaki disease (KD) is a systemic vasculitis and it predominantly affects young
      children. Fever with rash is a common presentation in children and is mostly due
      to a viral illness needing symptomatic treatment. However, KD should be
      considered if the child has a high fever lasting for more than 5 days and has got
      other cardinal features of KD. It is important to get the diagnosis correct as
      cardiac complications can only be reduced when intravenous immunoglobulin is
      administered within a critical time frame (maximum 10 days) from the onset of the
      illness. Nurses play a vital role in managing and supporting children and their
      families, both in the community and the hospital setting.

PMID- 23545548
TI  - Will health visiting survive?

PMID- 23545549
TI  - Professional indemnity: are you insured?

PMID- 23545550
TI  - Bereavement and the fallout for nurses.

PMID- 23545551
TI  - The assessment and management of falls in residential care settings.
AB  - Care of the older person has become more specialised in Ireland particularly
      since the introduction of national and international healthcare standards. In
      this regard, older people are receiving more evidence-based quality care when
      living in long-term healthcare facilities in Ireland. Assessment and management
      of falls is currently high on the quality agenda in terms of measuring quality
      outcomes. Clinical practice is being standardised using evidence-based practice
      and research. Residential care nurses caring for older people in Ireland are
      required to demonstrate clinical competence when assessing and managing falls in
      the residential care setting. Healthcare legislation, policy and in-service
      education, occurring in both the public and private sector, require a
      multidisciplinary-team approach. This article addresses the nursing priorities
      regarding falls assessment and management strategies that residential nurses
      should consider when caring for the older person at risk of falling.

PMID- 23545552
TI  - Focus group interviews part 3: analysis.
AB  - The use of focus group interviews as a means of qualitative data collection has
      gained popularity in health service research in recent years. Despite their
      popularity, analysing qualitative data-particularly focus-group interviews-poses
      a challenge to most researchers. This article follows the authors' previous
      articles on; focus group theory, and the preparation and conduct of focus group
      interviews. Despite the publications on conducting focus groups, little
      information exists regarding the analysis of data gathered in such groups in
      health services. The present paper focuses on the concepts and application of
      data analysis and the use of analysis frameworks. The article aims to assist
      researchers and provide practical steps for the analysis of focus-group data.
      Thus, the authors provide a framework for analysing focus group data through
      identifying data analysis techniques suited for the study of these data.

PMID- 23545553
TI  - How patient beliefs affect adherence to prescribed medication regimens.
AB  - This article analyses the evidence relating to patients' beliefs and adherence to
      prescribed medication regimens. Between 30% and 50% of patients question the
      appropriateness and effectiveness of their prescribed medication and often do not
      comply with their regimens, which means significant amounts of NHS cash is wasted
      on unused medications. A critical analysis of published literature from several
      electronic databases and professional journals was undertaken. This showed a
      strong qualitative relationship between patients' beliefs about their medication
      and adherence to regimens. Better communication with and involvement of patients
      in the decision-making process of medication prescribing is significant in
      reducing misconceptions, improve beliefs and promote adherence to prescribed
      regimens.

PMID- 23545554
TI  - Gastro-oesophageal reflux. Part 2: medical treatment.
AB  - INTRODUCTION AND BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a
      chronic disease characterised by retrograde movement of stomach contents into the
      oesophagus. It causes heartburn and oesophagitis and adversely affects quality of
      life. If left untreated it can lead to oesophageal stricture and carcinoma. The
      prevalence in Western countries is 30%. This paper presents a comparative review
      of the effectiveness of Omeprazole with Ranitidine for treatment of GORD.
      METHODS: A search for English language studies on adults was conducted using
      three databases, MEDLINE, EMBASE and the Cochrane Central Register of RCTs.
      Thirty relevant studies were included in the review. FINDINGS: Omeprazole is more
      effective in controlling heartburn symptoms, healing oesophagitis, improving
      quality of life and preventing relapses than Ranitidine, but takes time to reach
      therapeutic effect. Ranitidine is more effective at relieving symptoms on an as
      required basis. CONCLUSIONS: Nurses need to be aware of the effectiveness and use
      of these medications so that patients can make informed treatment choices and
      develop a greater understanding of the importance of concordance with
      prescriptions.

PMID- 23545555
TI  - Advancing practice: from staff nurse to nurse consultant. Part 5: leadership.

PMID- 23545556
TI  - Placements: stepping stones to excellent care.

PMID- 23545557
TI  - NICE consultation on developing social care standards.

PMID- 23545558
TI  - Mental health services must improve care provision.

PMID- 23545559
TI  - Having the courage to care-lessons learnt after Mid Staffordshire.

PMID- 23545560
TI  - Electroactive nanoparticle directed assembly of functionalized graphene
      nanosheets into hierarchical structures with hybrid compositions for flexible
      supercapacitors.
AB  - Hierarchical structures of hybrid materials with the controlled compositions have
      been shown to offer a breakthrough for energy storage and conversion. Here, we
      report the integrative assembly of chemically modified graphene (CMG) building
      blocks into hierarchical complex structures with the hybrid composition for high
      performance flexible pseudocapacitors. The formation mechanism of hierarchical
      CMG/Nafion/RuO2 (CMGNR) microspheres, which is triggered by the cooperative
      interplay during the in situ synthesis of RuO2 nanoparticles (NPs), was
      extensively investigated. In particular, the hierarchical CMGNR microspheres
      consisting of the aggregates of CMG/Nafion (CMGN) nanosheets and RuO2 NPs
      provided large surface area and facile ion accessibility to storage sites, while
      the interconnected nanosheets offered continuous electron pathways and mechanical
      integrity. The synergistic effect of CMGNR hybrids on the supercapacitor (SC)
      performance was derived from the hybrid composition of pseudocapacitive RuO2 NPs
      with the conductive CMGNs as well as from structural features. Consequently, the
      CMGNR-SCs showed a specific capacitance as high as 160 F g(-1), three-fold higher
      than that of conventional graphene SCs, and a capacitance retention of >95% of
      the maximum value even after severe bending and 1000 charge-discharge tests due
      to the structural and compositional features.

PMID- 23545561
TI  - Ultrasound-assisted surfactant-enhanced emulsification microextraction with
      solidification of floating organic droplet followed by high performance liquid
      chromatography for the determination of strobilurin fungicides in fruit juice
      samples.
AB  - A novel method, ultrasound-assisted surfactant-enhanced emulsification
      microextraction with solidification of floating organic droplet (UASEME-SFOD),
      has been developed for the extraction of four strobilurin fungicides (kresoxim
      methyl, picoxystrobin, pyraclostrobin and trifloxystrobin) in fruit juices. In
      the UASEME-SFOD technique, Tween 80 was used as emulsifier, and 1-undecanol was
      used as extraction solvent without using any organic dispersive solvent. Several
      parameters that affect the extraction efficiency, such as the kind and volume of
      extraction solvent, the type and concentration of the surfactant, extraction
      time, extraction temperature and salt addition were investigated and optimized.
      Under the optimum extraction condition, the method yields a linear calibration
      curve in the concentration range from 5 to 10,000 ng mL(-1) for the targeted
      analytes with the correlation coefficient ranging from 0.9991 to 0.9998. The
      enrichment factors were in the range between 95 and 135, and the limits of
      detection of the method were 2-4 ng mL(-1). The fruit juice samples were
      successfully analyzed using the proposed method, and the relative recoveries at
      fortified levels of 50 and 100 ng mL(-1) were in the range of 82.6-97.5%.

PMID- 23545562
TI  - Liquid chromatography/tandem mass spectrometry method for quantitative estimation
      of polyethylene glycol 400 and its applications.
AB  - A rapid sensitive and selective MRM based method for the determination of
      polyethylene glycol 400 (PEG 400) in rat plasma was developed using liquid
      chromatography/tandem mass spectrometry (LC-MS/MS). PEG 400 and telmisartan
      (Internal standard) were extracted from rat plasma with acetonitrile and analysed
      on C18 column (Waters Xbridge, 50*4.6 mm, 3.5 MUm) with the mobile phase (A -
      0.1% formic acid in water; B - methanol). A generic gradient method with a short
      run time of 3.5 min was developed for the analysis of PEG 400. A total of nine
      oligomers were identified for PEG 400. The most abundant ions corresponding to
      PEG 400 oligomers at m/z 327, 371, 432, 476, 520, 564, 608, 652 and 696 with
      daughter ion at m/z 89 were selected for multiple reaction monitoring (MRM) in
      electrospray mode of ionisation. Analyte peak area of the oligomers was summed up
      to calculate the plasma concentrations of total PEG 400. The standard curve was
      linear (0.9954) over the concentration range of 1.01-1013.40 MUg/mL. The lower
      limit of quantitation for PEG 400 was 1.01 MUg/mL using 50 MUL plasma. The
      coefficient of variation and relative error for inter and intraassay at three QC
      levels were 2.31-13.34 and -7.99 to 0.37, respectively. The method was validated
      for various parameters such as extraction recovery, matrix effect, autosampler
      stability, benchtop stability, freeze thaw stability, long term stability and was
      proved to be consistent across three QC levels with overall %CV less than 15. The
      developed method was successfully applied to the absolute bioavailability study
      of PEG 400 in male Sprague Dawley rats. Plasma concentrations of PEG 400 was
      measured after administration through oral and intravenous routes in male Sprague
      Dawley rats at a dose of 3.38 g/kg. Pharmacokinetic (PK) parameters were
      characterised by performing the analysis using Phoenix Winnonlin software (v
      6.3). PEG 400 has good oral bioavailability with mean absolute bioavailability of
      47.23%. Plasma concentration profile/PK parameters of PEG 400 was established in
      both intravenous and oral routes, which helps to qualify the analytical batch of
      NCEs having spiky plasma concentration profiles/erratic results. Purity of the
      PEG 400 oligomers was estimated using ELSD detection. Differences in
      pharmacokinetics of oligomers was studied. It was found that with increase in
      molecular weight of the oligomer, a decrease in absolute bioavailability was
      observed.

PMID- 23545563
TI  - Failure to engage hospitalized elderly patients and their families in advance
      care planning.
AB  - IMPORTANCE: Advance care planning can improve patient-centered care and
      potentially reduce intensification of care at the end of life. OBJECTIVES: To
      inquire about patients' advance care planning activities before hospitalization
      and preferences for care from the perspectives of patients and family members, as
      well as to measure real-time concordance between expressed preferences for care
      and documentation of those preferences in the medical record. DESIGN: Prospective
      study. SETTING: Twelve acute care hospitals in Canada. PARTICIPANTS: Elderly
      patients who were at high risk of dying in the next 6 months and their family
      members. MAIN OUTCOME MEASURES: Responses to an in-person administered
      questionnaire and concordance of expressed preferences and orders of care
      documented in the medical record. RESULTS: Of 513 patients and 366 family members
      approached, 278 patients (54.2%) and 225 family members (61.5%) consented to
      participate. The mean ages of patients and family members were 80.0 and 60.8
      years, respectively. Before hospitalization, most patients (76.3%) had thought
      about end-of-life (EOL) care, and only 11.9% preferred life-prolonging care;
      47.9% of patients had completed an advance care plan, and 73.3% had formally
      named a surrogate decision maker for health care. Of patients who had discussed
      their wishes, only 30.3% had done so with the family physician and 55.3% with any
      member of the health care team. Agreement between patients' expressed preferences
      for EOL care and documentation in the medical record was 30.2%. Family members'
      perspectives were similar to those of patients. CONCLUSIONS AND RELEVANCE: Many
      elderly patients at high risk of dying and their family members have expressed
      preferences for medical treatments at the EOL. However, communication with health
      care professionals and documentation of these preferences remains inadequate.
      Efforts to reduce this significant medical error of omission are warranted.

PMID- 23545564
TI  - A self-powered microfluidic origami electrochemiluminescence biosensing platform.
AB  - A self-powered 3D microfluidic electrochemiluminescence biosensing platform,
      integrated with a stable, environmentally-friendly and noble metal-free primary
      battery, was developed for the first time based on the principle of origami.

PMID- 23545566
TI  - Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine
      macrophages via Toll-like receptor 4 and stimulate bacterial clearance.
AB  - Sphingobacterium spiritivorum has five unusual sphingophospholipids (SPLs). Our
      previous study determined the complete chemical structures of these SPLs. The
      compositions of the long-chain bases/fatty acids in the ceramide portion,
      isoheptadecasphingosine/isopentadecanoate or isoheptadecasphingosine/2-hydroxy
      isopentadecanoate, are characteristic. The immune response against bacterial
      lipid components is considered to play important roles in microbial infections.
      It is reported that several bacterial sphingolipids composed of ceramide are
      recognized by CD1-restricted T and NKT cells and that a non-peptide antigen is
      recognized by gammadelta T cells. In this study, we demonstrated that these
      bacterial SPLs activated murine bone marrow macrophages (BMMs) via Toll-like
      receptor (TLR) 4 but not TLR2, although they slightly activated CD1d-restricted
      NKT and gammadeltaT cells. Interestingly, this TLR 4-recognition pathway of
      bacterial SPLs involves the fatty acid composition of ceramide in addition to the
      sugar moiety. A non-hydroxy fatty acid composed of ceramide was necessary to
      activate murine BMMs. The bacterial survival was significantly higher in TLR4-KO
      mice than in TLR2-KO and wild-type mice. The results indicate that activation of
      the TLR4-dependent pathway of BMMs by SPLs induced an innate immune response and
      contributed to bacterial clearance.

PMID- 23545567
TI  - Autophagy in obesity and atherosclerosis: Interrelationships between cholesterol
      homeostasis, lipoprotein metabolism and autophagy in macrophages and other
      systems.
AB  - The incidence of diseases characterized by a dysregulation of lipid metabolism
      such as obesity, diabetes and atherosclerosis is rising at alarming rates,
      driving research to uncover new therapies to manage dyslipidemias and resolve the
      metabolic syndrome conundrum. Autophagy and lipid homeostasis - both ancient
      cellular pathways - have seemingly co-evolved to share common regulatory
      elements, and autophagy has emerged as a prominent mechanism involved in the
      regulation of lipid metabolism. This review highlights recent findings on the
      role of autophagy in the regulation of cellular cholesterol homeostasis and
      lipoprotein metabolism, with special emphasis on macrophages. From modulation of
      inflammation to regulation of cellular cholesterol levels, a protective role for
      autophagy in atherosclerosis is emerging. The manipulation of autophagic activity
      represents a new possible therapeutic approach for the treatment complex
      metabolic disorders such as obesity and the metabolic syndrome.

PMID- 23545568
TI  - Stable and high-rate overcharge protection for rechargeable lithium batteries.
AB  - Rechargeable lithium or lithium-ion cells can be overcharge-protected by an
      electroactive polymer composite separator. The use of non-woven fibrous membranes
      instead of conventional microporous membranes as the composite substrates allowed
      better distribution of the electroactive polymer, which led to improved
      utilization and a 40-fold increase in sustainable current density. For the first
      time, stable overcharge protection for hundreds of cycles was demonstrated in
      several cell chemistries, including LiNi1/3Co1/3Mn1/3O2, LiFePO4, and spinel
      Li1.05Mn1.95O4 half-cells. Protection at a charging rate as high as 5 C was
      achieved at a steady state cell potential below 4.85 V.

PMID- 23545569
TI  - Psychological distress in parents of children with advanced cancer.
AB  - IMPORTANCE: Parent psychological distress can impact the well-being of childhood
      cancer patients and other children in the home. Recognizing and alleviating
      factors of parent distress may improve overall family survivorship experiences
      following childhood cancer. OBJECTIVES: To describe the prevalence and factors of
      psychological distress (PD) among parents of children with advanced cancer.
      DESIGN: Cohort study embedded within a randomized clinical trial (Pediatric
      Quality of Life and Evaluation of Symptoms Technology [PediQUEST] study).
      SETTING: Multicenter study conducted at 3 children's hospitals (Boston Children's
      Hospital, Children's Hospital of Philadelphia, and Seattle Children's Hospital).
      PARTICIPANTS: Parents of children with advanced (progressive, recurrent, or
      refractory) cancer. MAIN OUTCOME MEASURE: Parental PD, as measured by the Kessler
      6 Psychological Distress Scale. RESULTS: Eighty-six of 104 parents completed the
      Survey About Caring for Children With Cancer (83% participation); 81 parents had
      complete Kessler-6 Psychological Distress Scale data. More than 50% of parents
      reported high PD and 16% met criteria for serious PD (compared with US prevalence
      of 2%-3%). Parent perceptions of prognosis, goals of therapy, child
      symptoms/suffering, and financial hardship were associated with PD. In
      multivariate analyses, average parent Kessler-6 Psychological Distress Scale
      scores were higher among parents who believed their child was suffering highly
      and who reported great economic hardship. Conversely, PD was significantly lower
      among parents whose prognostic understanding was aligned with concrete goals of
      care. CONCLUSIONS AND RELEVANCE: Parenting a child with advanced cancer is
      strongly associated with high to severe levels of PD. Interventions aimed at
      aligning prognostic understanding with concrete care goals and easing child
      suffering and financial hardship may mitigate parental PD.

PMID- 23545570
TI  - Interface engineering of graphene for universal applications as both anode and
      cathode in organic photovoltaics.
AB  - The high transparency of graphene, together with its good electrical conductivity
      and mechanical robustness, enable its use as transparent electrodes in
      optoelectronic devices such as solar cells. While initial demonstrations of
      graphene-based organic photovoltaics (OPV) have been promising, realization of
      scalable technologies remains challenging due to their performance and,
      critically, poor device reproducibility and yield. In this work, we demonstrate
      by engineering the interface between graphene and organic layers, device
      performance and yield become close to devices using indium tin oxide. Our study
      confirms that the key issue leading to the poor performance or irreproducibility
      in graphene-based OPV originates from the graphene interface, and can be
      addressed by a simple interface modification method introduced in this work. We
      also show similar approach allows graphene to be used as cathode in inverted OPV
      geometry, thereby demonstrating the universal application of graphene as
      transparent conductors for both the anode and cathode.

PMID- 23545572
TI  - Mechanisms of Francisella tularensis intracellular pathogenesis.
AB  - Francisella tularensis is a zoonotic intracellular pathogen and the causative
      agent of the debilitating febrile illness tularemia. Although natural infections
      by F. tularensis are sporadic and generally localized, the low infectious dose,
      with the ability to be transmitted to humans via multiple routes and the
      potential to cause life-threatening infections, has led to concerns that this
      bacterium could be used as an agent of bioterror and released intentionally into
      the environment. Recent studies of F. tularensis and other closely related
      Francisella species have greatly increased our understanding of mechanisms used
      by this organism to infect and cause disease within the host. Here, we review the
      intracellular life cycle of Francisella and highlight key genetic determinants
      and/or pathways that contribute to the survival and proliferation of this
      bacterium within host cells.

PMID- 23545573
TI  - Erythropoiesis: development and differentiation.
AB  - Through their oxygen delivery function, red blood cells are pivotal to the
      healthy existence of all vertebrate organisms. These cells are required during
      all stages of life--embryonic, fetal, neonatal, adolescent, and adult. In the
      adult, red blood cells are the terminally differentiated end-product cells of a
      complex hierarchy of hematopoietic progenitors that become progressively
      restricted to the erythroid lineage. During this stepwise differentiation
      process, erythroid progenitors undergo enormous expansion, so as to fulfill the
      daily requirement of ~2 * 10(11) new erythrocytes. How the erythroid lineage is
      made has been a topic of intense research over the last decades. Developmental
      studies show that there are two types of red blood cells--embryonic and adult.
      They develop from distinct hemogenic/hematopoietic progenitors in different
      anatomical sites and show distinct genetic programs. This article highlights the
      developmental and differentiation events necessary in the production of
      hemoglobin-producing red blood cells.

PMID- 23545575
TI  - Historical overview of transplantation.
AB  - Except for legends and claims of miracles, most histories of transplantation
      cover only the last 60 years because there were no earlier successes. However,
      the story of even this era has been documented in such rich detail that a full
      account would fill several volumes. Thus, this brief summary must be limited to
      highly selected "landmarks." Some landmarks had an immediate impact, but the
      importance of others went unrecognized for decades. Some findings that deserved
      landmark status were overlooked or forgotten, whereas others of no biological
      significance had major impact. Placing these events in perspective is
      challenging. Several of transplantation's pioneers are still alive, and most of
      the others are within living memory. Virtually all of them have produced their
      own accounts. For the most part, they agree on what the "landmarks" are, but
      their differences in emphasis and perspective make an interesting story.

PMID- 23545574
TI  - Model systems for cardiovascular regenerative biology.
AB  - There is an urgent clinical need to develop new therapeutic approaches to treat
      heart failure, but the biology of cardiovascular regeneration is complex. Model
      systems are required to advance our understanding of biological mechanisms of
      cardiac regeneration as well as to test therapeutic approaches to regenerate
      tissue and restore cardiac function following injury. An ideal model system
      should be inexpensive, easily manipulated, easily reproducible, physiologically
      representative of human disease, and ethically sound. In this review, we discuss
      computational, cell-based, tissue, and animal models that have been used to
      elucidate mechanisms of cardiovascular regenerative biology or to test proposed
      therapeutic methods to restore cardiac function following disease or injury.

PMID- 23545576
TI  - Association of peroxisome proliferator-activated receptor alpha/delta/gamma with
      obesity, and gene-gene interaction, in the Chinese Han population.
AB  - BACKGROUND: We investigated the association of 10 single-nucleotide polymorphisms
      (SNPs) in the peroxisome proliferator-activated receptors (PPARs) with obesity
      and the additional role of gene-gene interaction. METHODS: Participants were
      recruited within the framework of the Prevention of Multiple Metabolic Disorders
      and MS in Jiangsu Province cohort population survey of an urban community in
      China. In total, 820 subjects (513 nonobese adults, 307 obese adults) were
      randomly selected, and no individuals were consanguineous. Ten SNPs (rs135539,
      rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158,
      rs3856806, and rs4684847) were genotyped and analyzed. RESULTS: After covariate
      adjustment, minor alleles of rs2016520 in PPARdelta and rs10865170 in PPARgamma
      were associated with lower BMI (P < 0.01 for all). Generalized multifactor
      dimensionality reduction analysis showed significant gene-gene interaction among
      rs2016520, rs9794, and rs10865170 in 3-dimensional models (P = 0.0010);
      prediction accuracy was 0.6011 and cross-validation consistency was 9/10. It also
      showed significant gene-gene interaction between rs2016520 and rs10865170 in all
      2-dimensional models (P = 0.0010); prediction accuracy was 0.6072 and cross
      validation consistency was 9/10. CONCLUSIONS: rs2016520 and rs10865170 were
      associated with lower obesity risk. In addition, interaction was identified among
      rs2016520, rs9794, and rs10865170 in obesity.

PMID- 23545577
TI  - Herpes zoster and subsequent risk of cancer: a population-based study.
AB  - BACKGROUND: In this cohort study, we investigated whether a diagnosis of herpes
      zoster (HZ) was associated with a higher risk of subsequent cancer as compared
      with the Taiwanese general population. METHODS: Data were obtained from the
      Taiwan National Health Insurance Research Database. In total, 38 743 patients who
      were aged 50 years or older and had received ambulatory care for HZ between 1997
      and 2006 were identified as the study cohort; 116 229 age- and sex-matched
      patients without HZ were included as the comparison cohort. We used Cox
      proportional hazards regression models to estimate the hazard ratios (HRs) for
      subsequent cancer, after controlling for potential confounders. RESULTS: The HR
      for subsequent cancer varied according to time since HZ diagnosis. The HR was
      1.58 (95% CI, 1.38-1.80) within the first year, 1.30 (95% CI, 1.15-1.46) between
      1 and 2 years, 1.10 (95% CI, 0.98-1.24) between 2 and 3 years, 1.02 (95% CI, 0.91
      1.15) between 3 and 4 years, and 1.08 (95% CI, 0.96-1.21) between 4 and 5 years.
      The risk of subsequent cancer, particularly lung cancer, was significantly higher
      during the first 2 years after initial diagnosis of HZ. CONCLUSIONS: Our findings
      suggest that an HZ diagnosis is a marker of occult malignancy, particularly in
      lung cancer. The HRs for cancer decreased gradually over time and were no longer
      significant after 2 years of follow-up, which indicates that the association
      between HZ and cancer is likely due to detection bias.

PMID- 23545571
TI  - Bacterial biofilms: development, dispersal, and therapeutic strategies in the
      dawn of the postantibiotic era.
AB  - Biofilm formation constitutes an alternative lifestyle in which microorganisms
      adopt a multicellular behavior that facilitates and/or prolongs survival in
      diverse environmental niches. Biofilms form on biotic and abiotic surfaces both
      in the environment and in the healthcare setting. In hospital wards, the
      formation of biofilms on vents and medical equipment enables pathogens to persist
      as reservoirs that can readily spread to patients. Inside the host, biofilms
      allow pathogens to subvert innate immune defenses and are thus associated with
      long-term persistence. Here we provide a general review of the steps leading to
      biofilm formation on surfaces and within eukaryotic cells, highlighting several
      medically important pathogens, and discuss recent advances on novel strategies
      aimed at biofilm prevention and/or dissolution.

PMID- 23545578
TI  - Suppression of renal cell carcinoma growth in vivo by forced expression of
      vascular endothelial growth inhibitor.
AB  - Vascular endothelial growth inhibitor (VEGI) has been associated with tumor
      related vasculature in certain malignancies. However, its implication in renal
      cell carcinoma (RCC), an angiogenesis-dependent tumor, remains unknown. In the
      present study, we investigated the role played by VEGI in RCC. The expression of
      VEGI was examined in human renal tissue and RCC cell lines using
      immunohistochemical staining and RT-PCR, respectively. The biological impact of
      modifying the expression of VEGI in RCC cells was evaluated using in vitro and in
      vivo models. We show that VEGI mRNA is expressed in a wide variety of human RCC
      cell lines, all of normal renal and most of RCC tissue specimens. VEGI protein
      expression was observed in normal renal tubular epithelial cells, but was
      decreased or absent in RCC specimens, particularly in tumors with high grade.
      Moreover, forced expression of VEGI led to an inhibition of vascular endothelial
      tube formation, decrease in the motility and adhesion of RCC cells in vitro.
      Interestingly, forced expression of VEGI had no bearing on growth, apoptosis and
      invasive capacity of RCC cells. However, tumor growth was reduced in xenograft
      models. Immunohistochemical staining showed that microvessel density decreased in
      VEGI forced expression xenograft tumor samples. Taken together, our findings
      showed that the expression of VEGI is decreased in RCC, particularly in tumors
      with higher grade. Together with its inhibitory effect on cellular motility,
      adhesion, vascular endothelial tube formation and tumor growth in vivo, this
      suggests that VEGI functions mainly through inhibition of angiogenesis and is a
      negative regulator of aggressiveness during the development and progression of
      RCC.

PMID- 23545579
TI  - Prognostic value of the diagnostic criteria distinguishing endometrial stromal
      sarcoma, low grade from undifferentiated endometrial sarcoma, 2 entities within
      the invasive endometrial stromal neoplasia family.
AB  - The World Health Organization (WHO 2003) recognizes 3 endometrial stromal
      neoplasms: noninvasive endometrial stromal nodule and the 2 invasive neoplasms,
      endometrial stromal sarcoma (ESS), low grade and undifferentiated endometrial
      sarcoma (UES). It is important to note that the WHO 2003 does not define moderate
      atypia (an important differentiating diagnostic criterion for ESS, low grade and
      UES), nor does it discuss its significance. Moreover, studies on reproducibility
      and additional prognostic value of other diagnostic features in large are
      lacking. Using strict definitions, we analyzed the agreement between routine and
      expert-review necrosis and nuclear atypia in 91 invasive endometrial stromal
      neoplasias (IESN). The overall 5-year and 10-year recurrence-free survival rate
      estimates of the 91 IESN patients were 82% and 75%, respectively. Necrosis was
      well reproducible, and nuclear atypia was reasonably well reproducible. The 10
      year recurrence-free survival rates for necrosis absent/inconspicuous versus
      prominent were 89% and 45% (P<0.001) and those for review-confirmed none/mild,
      moderate, severe atypia were 90%, 30%, and <20% (P<0.00001). Therefore, cases
      with moderate/severe atypia should be grouped together. Nuclear atypia and
      necrosis had independent prognostic values (Cox regression). Once these features
      were taken into account, no other feature had an independent additional
      prognostic value, including mitotic count. Using "none/mild atypia, necrosis
      absent/inconspicuous" as ESS, low grade versus "moderate/severe atypia present or
      necrosis present" as UES resulted in 68 ESS, low grade and 23 UES cases with
      disease-specific overall mortality-free survival of 99% versus 48% (P<0.00001,
      hazard ratio=45.4). When strictly defined microscopic criteria are used, the WHO
      2003 diagnoses of ESS, low grade and UES are well reproducible and prognostically
      strong.

PMID- 23545580
TI  - Ambipolar, low-voltage and low-hysteresis PbSe nanowire field-effect transistors
      by electrolyte gating.
AB  - Semiconductor nanowire field-effect transistors (FETs) are interesting for
      fundamental studies of charge transport as well as possible applications in
      electronics. Here, we report low-voltage, low-hysteresis and ambipolar PbSe
      nanowire FETs using electrolyte-gating with ionic liquids and ion gels. We obtain
      balanced hole and electron mobilities at gate voltages below 1 V. Due to the
      large effective capacitance of the ionic liquids and thus high charge carrier
      densities electrolyte-gated nanowire FETs are much less affected by external
      doping and traps than nanowire FETs with traditional dielectrics such as SiO2.
      The observed current-voltage characteristics and on/off ratios indicate almost
      completely transparent Schottky barriers and efficient ambipolar charge injection
      into a low band gap one-dimensional semiconductor. Finally, we explore the
      possibility of applying these ambipolar nanowire FETs in complementary inverters
      for printed electronics.

PMID- 23545581
TI  - Two new drugs for homozygous familial hyperchelesterolemia.

PMID- 23545582
TI  - Raxibacumab for anthrax.

PMID- 23545583
TI  - In brief: FDA azithromycin warning.

PMID- 23545584
TI  - Multiple roles of SOCS proteins: differential expression of SOCS1 and SOCS3 in
      atherosclerosis.
AB  - Pro-inflammatory cytokines play a key pathogenic role in atherosclerosis, which
      are induced by the Janus kinase/signal transducer and activator of transduction
      (JAK/STAT) pathway. Furthermore, the JAK/STAT pathway is negatively regulated by
      the suppressor of cytokine signaling (SOCS) proteins. However, the change in SOCS
      expression levels and the correlation between SOCS expression and cholesterol
      levels in atherosclerosis is not yet well understood. To this end, a mouse model
      of atherosclerosis was established using apolipoprotein-deficient (ApoE(-/-))
      mice. The mice were fed either a chow or high-fat diet. The mRNA and protein
      expression of SOCS1 and SOCS3 in plaque and vessels were determined at different
      time points. Furthermore, SOCS1 and SOCS3 mRNA expression was detected in the
      peripheral blood mononuclear cells (PBMCs) obtained from 18 male subjects with no
      coronary heart disease (non-CHD) population. The expression of SOCS1 in the ApoE(
      /-) mice first increased and then decreased and the high-fat diet accelerated the
      appearance of the peak; the expression of SOCS3 increased with the increased
      feeding duration, and this trend was more pronounced in the mice fed the high-fat
      diet. SOCS1/CD68 and SOCS3/CD68 showed opposite trends in expression with the
      increased duration of the high-fat diet. Interleukin-6 (IL-6) expression in the
      main aorta of the ApoE(-/-) mice fed the high-fat diet also increased with the
      increased feeding duration. In the non-CHD population, the total serum
      cholesterol levels positively correlated with SOCS3 mRNA expression in the PBMCs
      (r=0.433, P=0.012). These results demonstrate the differential expression of
      SOCS1 and SOCS3 in atherosclerosis and suggest that SOCS3, together with IL-6 may
      promote the formation and development of atherosclerosis.

PMID- 23545586
TI  - Patellofemoral osteoarthritis after Insall's proximal realignment for recurrent
      patellar dislocation.
AB  - PURPOSE: The aim of the present study was to retrospectively investigate the
      development of patellofemoral osteoarthritis after the historical Insall's
      proximal realignment for patellar stabilisation in patients with recurrent
      patellar dislocation. Furthermore, risk factors for recurrent patellar
      dislocation and for patellofemoral osteoarthritis development were evaluated.
      METHODS: Forty-two patients underwent patellofemoral stabilising surgery by the
      historic Insall's proximal realignment; they were evaluated with a mean follow-up
      period of 52 months. Plain radiography was used to document osteoarthritic
      changes by using the Iwano classification. MRIs obtained at the latest follow-up
      were evaluated for patellofemoral cartilage lesions. Univariate and multivariate
      logistic regression analyses were performed to evaluate the influence of
      trochlear dysplasia, tibial tubercle-trochlear groove distance and patellar
      height on redislocation. Pearson's chi (2) and the Spearman's correlation tests
      were used to assess a possible correlation between trochlear dysplasia and
      patellar dislocation, as well as between instability and development of
      patellofemoral osteoarthritis. RESULTS: At the latest follow-up, plain
      radiographs showed a significant increase in patellofemoral osteoarthritis
      (grades II-IV according to the Iwano classification) in 18 patients (43%)
      compared with 4 patients (10%) at the time of surgery (P = 0.001). Patellofemoral
      cartilage lesions (grades II-IV) were detected in 18 patients (43 %) on MRI. Nine
      patients (21%) had at least one incidence of redislocation at follow-up.
      Estimated redislocation-associated risk factors could not be determined.
      Trochlear dysplasia had a significant impact on patellofemoral osteoarthritis
      development (P = 0.001), whereas recurrent patellar instability had none (n.s.).
      CONCLUSION: Insall's proximal realignment technique leads to a significant
      progression of patellofemoral osteoarthritis. No risk factors for redislocation
      could be found; however, the presence of trochlear dysplasia did correlate with
      patellofemoral osteoarthritis. LEVEL OF EVIDENCE: IV.

PMID- 23545587
TI  - Decay of gamma-H2AX foci correlates with potentially lethal damage repair in
      prostate cancer cells.
AB  - To determine the relationship between ionizing radiation-induced levels of gamma
      H2AX foci and cell survival in cultured prostate cancer cell lines, three
      prostate cancer cell lines: LNCaP (wt TP53), DU145 (mut TP53) and PC3 (TP53
      null), were studied. For gamma-H2AX foci induction, cells were irradiated with a
      single dose of 2 Gy and foci levels were studied at 30 min and 24 h after
      irradiation. Cell survival was determined by clonogenic assay, directly and 24 h
      after irradiation with doses ranging from 0 to 8 Gy. Irradiation was performed
      with a Siemens Stabilipan 250 KeV X-ray machine at a dose rate of approximately 3
      Gy/min. Survival curves were analyzed using the linear-quadratic model
      S(D)/S(0)=exp-(alphaD+betaD2). LNCaP cells clearly demonstrated potentially
      lethal damage repair (PLDR) which was assessed as increased survival levels after
      delayed plating as compared to cells plated immediately after irradiation. DU145
      cells demonstrated only a slight PLDR and PC3 cells did not show PLDR at all.
      Levels of gamma-H2AX foci were significantly decreased in all cell lines at 24 h
      after irradiation, compared to levels after 30 min. The LNCaP cells which
      demonstrated a clear PLDR also showed the largest decay in the number of gamma
      H2AX foci. In addition, the PC cells which did not show PLDR had the lowest decay
      of gamma-H2AX foci. A clear correlation was demonstrated between the degree of
      decay of gamma-H2AX foci and PLDR.

PMID- 23545588
TI  - Glomerular disease: MicroRNA-193a--a new pathogenic player and target in focal
      segmental glomerulosclerosis.

PMID- 23545589
TI  - Vasculitis: Epitope specificity responsible for MPO-ANCA pathogenicity.

PMID- 23545590
TI  - Transplantation: Proteinuria in kidney transplantation: an ongoing story.

PMID- 23545591
TI  - Treatment of IgA nephropathy and Henoch-Schonlein nephritis.
AB  - Treatment options for primary IgA nephropathy (IgAN) and Henoch-Schonlein
      nephritis are still largely based on opinion or weak evidence. Consequently, the
      recent KDIGO Clinical Practice Guidelines for Glomerulonephritis have assigned
      low levels of evidence for almost all recommendations and suggestions related to
      these two diseases. In this Review, we describe an algorithm for structuring the
      treatment of IgAN depending on the clinical scenario. Key to therapeutic decision
      making is assessment of the individual's prognosis. Clinical parameters (such as
      proteinuria, hypertension, and impaired glomerular filtration rate [GFR]) are
      used to estimate risk, but the clinical value of the novel histological Oxford
      MEST classification remains to be determined. If these parameters indicate a risk
      of progressive GFR loss, comprehensive supportive care remains the mainstay of
      therapy. Two large trials, STOP-IgAN and TESTING, are underway to evaluate the
      value of adding corticosteroids after initiating such supportive care. At
      present, little evidence exists to suggest that any other immunosuppressive
      therapy beyond corticosteroids is effective in either IgAN or Henoch-Schonlein
      nephritis.

PMID- 23545592
TI  - Role of methotrexate polyglutamation and reduced folate carrier 1 (RFC1) gene
      polymorphisms in clinical assessment indexes.
AB  - The aims of the present study were to define inter-individual differences in
      response to methotrexate (MTX) through MTX polyglutamate (MTX-PG) levels in red
      blood cells (RBC) and MTX-related gene polymorphisms. A total of 145 rheumatoid
      arthritis patients were recruited. MTX-PG1-5 concentrations in RBC were measured,
      and 11 single nucleotide polymorphisms, all in MTX-related genes involved in the
      folate pathway, were analyzed. Disease activity was also assessed. There was no
      direct relationship between any MTX-PG concentration and the patient's disease
      condition, but detectability of MTX-PG5 was extracted as a candidate marker for
      response to MTX. When disease activity was compared between patients in which MTX
      PG5 was detectable and undetectable, all indexes except the visual analog scale
      (VAS) and C-reactive protein (CRP) were found to be significantly lower in the
      former patients. Reduced folate carrier 1 (RFC1) 80G>A was significantly
      associated with the detectability of MTX-PG5; detectability of MTX-PG5 was lower
      in patients with the A mutant allele. The present study suggests that
      detectability of MTX-PG5 in RBC is a possible biomarker for response to MTX, and
      the RFC1 80G>A mutation is associated with low detectability of MTX-PG5.
      Prospective studies with a sufficient number of patients are needed to confirm
      the present findings.

PMID- 23545593
TI  - A case-report of unpredictable and massive voriconazole intoxication in a patient
      with extensive CYP2C19 and CYP2C9 polymorphisms.
AB  - This case-report describes a massive voriconazole (VRZ) intoxication in a patient
      with a poor metabolizer profile, highlighted by low plasma main metabolite
      concentrations (N-oxide voriconazole), despite an extensive genetic profile for
      CYP2C19 and CYP2C9. The patient was treated with a therapeutic dose of VRZ but
      developed a neurotoxicity leading to hallucinations and coma while the plasma
      concentration of VRZ reached an exceptional level (20.0 ug/mL on day 10 of the
      treatment). Since neurological disorders diminished in parallel with the decrease
      of VRZ plasma concentrations, the coma was likely due to VRZ. The VRZ half-life,
      calculated to 58 h in this patient, was by far higher than the values reported in
      the literature. While VRZ concentrations slowly decreased, the N-oxide
      voriconazole concentrations slowly increased from day 15. Hypotheses for this
      lack of metabolization of VRZ are an inhibition of the metabolism by
      esomeprazole, a saturation of the metabolism or an enzymatic auto-inhibition of
      VRZ metabolism but none of these hypotheses have yet been explored. This case
      report of unpredictable accumulation of VRZ in a patient without any genetic risk
      factor is an advocacy for systematic therapeutic drug monitoring of VRZ.

PMID- 23545594
TI  - Dysregulations of intestinal and colonic UDP-glucuronosyltransferases in rats
      with type 2 diabetes.
AB  - Diabetes mellitus is a chronic disease of complex metabolic disorder associated
      with various types of complications. UDP-glucuronosyltransferases (UGTs), the
      major phase II conjugation enzymes, mediate the metabolism of both drugs and
      endogenous metabolites that may raise great concerns in the condition of
      diabetes. The aim of this study was to determine whether diabetes could affect
      UGTs in the intestinal and colonic tract. A high-fat diet combined with low-dose
      streptozotocin was used to induce a type 2 diabetic model in rats. The mRNA
      levels and enzymatic activities of UGT1A1, -1A6, and -1A7 in the diabetic
      intestine and colon were higher than those in nondiabetic rats. In contrast, both
      the activity and mRNA level of UGT2B1 in diabetic rats were lower than those in
      nondiabetic rats. Notably, the diabetic intestine and colon exhibited an
      inflammatory state with increased pro-inflammatory cytokines. Various
      transcriptional factors involved in UGT regulation were unanimously upregulated
      in the diabetic intestine and colon. These findings strongly suggest that the
      regulating pathways of the UGT1 family are adaptively upregulated in the diabetic
      gastrointestinal tract. Given the essential regulatory role of the
      gastrointestinal site in drug disposition, such changes in UGTs may have a
      dynamic and complex impact on therapeutic drugs and endogenous metabolomes.

PMID- 23545595
TI  - Transventricular endoscopic biopsy of suprasellar tumors: a pediatric case
      series.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the efficacy
      and safety of transventricular neuroendoscopic biopsies in pediatric patients
      with suprasellar tumors. METHODS: Twenty-three pediatric patients (12 males and
      11 females) with suprasellar tumors underwent transventricular neuroendoscopic
      biopsy at our institute by a single surgeon from 2000 to 2011. Neuronavigation
      has been combined with endoscopic procedures since 2008. Neuroendoscopic biopsies
      were performed to verify the histopathological diagnosis of neoplasms and to plan
      appropriate treatment strategies. RESULTS: Neuroendoscopic biopsy specimens were
      appropriate for diagnosis in 22 of the 23 patients (95.7%) and revealed 14 germ
      cell tumors (12 germinomas, one choriocarcinoma, and one immature teratoma),
      seven astrocytomas, and one craniopharyngioma. Subsequent treatment modalities
      including chemotherapy, radiation therapy, or microscopic surgery were determined
      according to the pathological findings. Seventeen of the 23 patients (73.9%)
      showed ventriculomegaly. Among them, ventriculomegaly in 14 patients was resolved
      after an endoscopic procedure and/or adjuvant chemotherapy, but the remaining
      three patients (17.6%) required a ventriculoperitoneal shunt to relieve the
      ventriculomegaly. The pathologic diagnosis of these three patients was uniformly
      a large astrocytoma. Navigational tracking was helpful to enter small ventricles
      and the narrow foramen of Monro in patients without hydrocephalus. No mortalities
      were related to the procedures, but three transient diabetes insipidus (13.0%)
      cases occurred but fully recovered before the patients received adjuvant therapy.
      CONCLUSION: Endoscopic biopsy is feasible and shows acceptable operation-related
      complications to obtain tissue from suprasellar tumors in pediatric patients.
      Navigation-assisted neuroendoscopic procedure improves the accuracy of the
      endoscopic approach. An associated endoscopic procedure can resolve
      hydrocephalus, but it has limitations with large ventricle-occupying tumors.

PMID- 23545596
TI  - Clinical outcomes and considerations of the lumbar interbody fusion technique for
      lumbar disk disease in adolescents.
AB  - PURPOSE: The posterior lumbar interbody fusion (PLIF) and transforaminal lumbar
      interbody fusion (TLIF) techniques are commonly used surgical methods for wide
      indications such as degeneration or trauma. Although they are rarely required for
      lumbar disk disease in younger patients, there are a few children and adolescents
      who are indicated for PLIF or TLIF for other reasons, such as congenital severe
      stenosis with or without lumbar instability that requires wide decompression or
      severe bony spur that need to be removed. In such cases, different
      pathophysiology and outcomes are expected compared with adult patients. METHODS:
      We retrospectively reviewed data of 23 patients who underwent PLIF or TLIF
      surgery when less than 20 years old. Clinical and radiographic outcomes were
      assessed during a mean of 36.4 months follow-up period. The indications of lumbar
      interbody fusion, success of fusion, complications, and visual analog scale (VAS)
      were analyzed. RESULTS: Radiographs of all patients taken 6 months after the
      surgery showed fusion. Clinical outcome was also satisfactory, with improvement
      of VAS score from 7.7 preoperatively to 2.3 at 6 months after surgery. Only one
      patient had reoperation due to adjacent segment disease. CONCLUSIONS: For
      adolescent patients with severe bony spur, massive central disk rupture, or
      severe spondylolisthesis, lumbar interbody fusion surgery has good surgical
      outcome with few complications.

PMID- 23545597
TI  - Dispersion-cancelled biological imaging with quantum-inspired interferometry.
AB  - Quantum information science promises transformative impact over a range of key
      technologies in computing, communication, and sensing. A prominent example uses
      entangled photons to overcome the resolution-degrading effects of dispersion in
      the medical-imaging technology, optical coherence tomography. The quantum
      solution introduces new challenges: inherently low signal and artifacts,
      additional unwanted signal features. It has recently been shown that entanglement
      is not a requirement for automatic dispersion cancellation. Such classical
      techniques could solve the low-signal problem, however they all still suffer from
      artifacts. Here, we introduce a method of chirped-pulse interferometry based on
      shaped laser pulses, and use it to produce artifact-free, high-resolution,
      dispersion-cancelled images of the internal structure of a biological sample. Our
      work fulfills one of the promises of quantum technologies: automatic-dispersion
      cancellation interferometry in biomedical imaging. It also shows how subtle
      differences between a quantum technique and its classical analogue may have
      unforeseen, yet beneficial, consequences.

PMID- 23545599
TI  - Enhancing the stability of polymer solar cells by improving the conductivity of
      the nanostructured MoO3 hole-transport layer.
AB  - This article demonstrates improvements in the operational stability of organic
      solar cells (OSCs) by taking advantage of the relationship between oxygen
      stoichiometry and conductivity in nanostructured metal oxide semiconductors (n
      MOS). OSCs in the inverted device configuration of ITO/Ca/P3HT:PCBM/MoO3/Ag were
      employed in the present study. A high degree of oxygen defects were introduced in
      the hole-conducting MoO3 layer by annealing the devices under vacuum (>=10(-5)
      mbar) for nominal temperature (120  degrees C) and time (10 min). The above
      devices had much higher operational stability, when tested following the ISOS-D-1
      (shelf) protocol, than control devices annealed conventionally, i.e., in nitrogen
      atmosphere. Employing current-voltage measurement as functions of temperature and
      photon flux, we show that the devices annealed under vacuum have a lesser density
      of traps than those annealed in nitrogen. The lesser trap density is shown to be
      beneficial in reducing the rate of electron recombination thereby increasing the
      operational stability of the corresponding device. A number of experiments were
      undertaken to show that the difference in the operation stability of the device
      results from the difference in conductivity of the nanostructured MoO3 hole
      transporting layer. The charge extraction by linear increasing voltage
      spectroscopy shows that charges are relaxed at the trap states in the device
      annealed in nitrogen whereas they are efficiently transported in the other
      device. We identify that building up of an interfacial potential barrier as a
      result of the charge relaxation at the trap states and the corresponding chemical
      changes in the devices annealed conventionally is the source of degradation of
      the device performance over time. To our knowledge, this is the first report that
      successfully overcomes hole-conductivity induced degradation in organic solar
      cells.

PMID- 23545603
TI  - Picture of the month. Hand-foot-and-mouth disease.

PMID- 23545605
TI  - Advice for patients. Adolescent volunteering.

PMID- 23545598
TI  - The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to
      enhance cognitive function in older adults.
AB  - IMPORTANCE: The prevalence of cognitive impairment and dementia are projected to
      rise dramatically during the next 40 years, and strategies for maintaining
      cognitive function with age are critically needed. Physical or mental activity
      alone result in relatively small, domain-specific improvements in cognitive
      function in older adults; combined interventions may have more global effects.
      OBJECTIVE: To examine the combined effects of physical plus mental activity on
      cognitive function in older adults. DESIGN: Randomized controlled trial with a
      factorial design. SETTING: San Francisco, California. PARTICIPANTS: A total of
      126 inactive, community-residing older adults with cognitive complaints.
      INTERVENTIONS: All participants engaged in home-based mental activity (1 h/d, 3
      d/wk) plus class-based physical activity (1 h/d, 3 d/wk) for 12 weeks and were
      randomized to either mental activity intervention (MA-I; intensive computer) or
      mental activity control (MA-C; educational DVDs) plus exercise intervention (EX
      I; aerobic) or exercise control (EX-C; stretching and toning); a 2 * 2 factorial
      design was used so that there were 4 groups: MA-I/EX-I, MA-I/EX-C, MA-C/EX-1, and
      MA-C/EX-C. MAIN OUTCOME MEASURES: Global cognitive change based on a
      comprehensive neuropsychological test battery. RESULTS: Participants had a mean
      age of 73.4 years; 62.7% were women, and 34.9% were Hispanic or nonwhite. There
      were no significant differences between the groups at baseline. Global cognitive
      scores improved significantly over time (mean, 0.16 SD; P < .001) but did not
      differ between groups in the comparison between MA-I and MA-C (ignoring exercise,
      P = .17), the comparison between EX-I and EX-C (ignoring mental activity, P =
      .74), or across all 4 randomization groups (P = .26). CONCLUSIONS AND RELEVANCE:
      In inactive older adults with cognitive complaints, 12 weeks of physical plus
      mental activity was associated with significant improvements in global cognitive
      function with no evidence of difference between intervention and active control
      groups. These findings may reflect practice effects or may suggest that the
      amount of activity is more important than the type in this subject population.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00522899.

PMID- 23545607
TI  - Idiopathic (primary) generalized epilepsy. Traditional versus new antiepileptic
      drugs.
AB  - Idiopathic generalized epilepsies (IGE) are genetic based seizures with normal
      neurologic exam, intelligence, and imaging studies. Based on the age of onset and
      prominent seizure type, different syndromes were identified. The purpose of this
      study is to summarize the characteristics, prognosis, and choices of
      antiepileptic drugs (AED) in common syndromes of IGE. In addition, we review the
      updated role of new AEDs in specific syndromes of IGE. The first choice AED is
      usually valproate. Most drug trials on the effects of new AEDs compared them with
      placebo and not valproate. However, some of the broad spectrum new AEDs may be
      considered as the first choice in specific conditions. In true refractory
      patients, combination therapy and vagal nerve stimulation could be the next
      option. In the proper management of IGE, neurologists should consider the
      predominant seizure type, patient gender, co-morbidities, and antiepileptic drugs
      that may aggravate a specific seizure type.

PMID- 23545606
TI  - Hypoxia inducible factor 1alpha-mediated LOX expression correlates with migration
      and invasion in epithelial ovarian cancer.
AB  - This study investigated the role of LOX in promoting invasion and metastasis of
      epithelial ovarian cancer in a hypoxic environment and its specific signal
      transduction pathway. Immunohistochemical detection of HIF-1alpha and LOX protein
      expression was performed on formalin-fixed paraffin sections of normal ovary,
      benign ovarian tumors, borderline and malignant epithelial ovarian tumor paraffin
      sample, using Mann-Whitney U test for independent comparisons and Wilcoxon signed
      ranks test for paired comparisons. HIF-1alpha and LOX were knocked down in
      epithelial ovarian cancer cells (EOC), and HIF-1alpha/LOX regulation mechanism
      and LOX catalytic activity under hypoxia/reoxygenation microenvironment were
      explored. Cell migration and invasion ability in LOX inhibited HO8910 cells were
      investigated under hypoxia/reoxygenation conditions, using matrigel cell invasion
      and migration assays. We found that HIF-1alpha and LOX are highly expressed in
      epithelial ovarian cancer tissues, and the expression of both proteins is
      significantly correlated with the tumor grade, tumor diameter and lymph node
      metastasis. HIF-1alpha expression is positively correlated with the expression of
      LOX. Specifically, the expression of LOX and HIF-1alpha markedly increases under
      hypoxic conditions and decreases after reoxygenation. siRNA knockdown of LOX or
      beta-aminoproprionitrile (betaAPN), an inhibitor of LOX activity, that attenuates
      LOX activity, downregulates HIF-1alpha protein expression and inhibits HO8910
      migratory and invasive abilities. LOX catalytic activity is significantly reduced
      under hypoxic conditions. Moreover, EOC cells display a marked increase in LOX
      dependent FAK/AKT activation and cell migration following hypoxia/reoxygenation.
      Collectively, our study demonstrates that the hypoxia-HIF-1alpha, LOX-FAK/AKT
      pathway regulates the migration and invasion of epithelial ovarian cancer cells
      under hypoxia/reoxygenation conditions, thus, promoting metastasis of ovarian
      cancer.

PMID- 23545608
TI  - Transcranial Doppler in brain death assessment. Perspective and implications in
      the Saudi Arabian health system.
AB  - Transcranial Doppler is a non-invasive, non-ionizing ultrasound-based imaging
      modality that is inexpensive with a short learning curve. It can be performed and
      interpreted at the bedside. This review explores the value of the transcranial
      Doppler technique as a confirmatory tool for brain death. The early confirmation
      of brain death enables the treating physicians in early decision-making and
      family counseling toward better care approaches, including the option of organ
      donation for transplantation at the appropriate time. We recommend this modality
      be incorporated as part of the brain death criteria in the Saudi Arabian health
      care system guidelines and utilized in different tiers of our hospital system.

PMID- 23545610
TI  - Protective effect of coenzyme Q10 in paclitaxel-induced peripheral neuropathy in
      rats.
AB  - OBJECTIVE: To investigate the possible protective effect of coenzyme Q10 (CQ10)
      on neuropathy in rats. METHODS: Experiments were conducted in the Department of
      Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey between
      January and March 2012. Forty rats were divided into 4 groups: group 1 (control),
      group 2 (paclitaxel), group 3 (control + CQ10), and group 4 (paclitaxel + CQ10).
      Group 2 and 4 rats received paclitaxel (2 mg/kg, intraperitoneally, on days 0, 2,
      4, 6). Group 3 and 4 rats were treated with CQ10 (10 mg/kg, intraperitoneally, on
      days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9). The rats that did not receive paclitaxel or
      CQ10 received vehicle. Mechanical allodynia tests were performed for each animal
      on day 0, 2, 6, 8, 10, 14, 16, 19, 39 and 41 for all groups with von Frey
      filaments. RESULTS: At day 0, mean mechanical withdrawal thresholds were similar
      among all groups. Starting from day 2, the threshold of the paclitaxel group
      decreased. Starting from day 10, paclitaxel+CQ10 treated rats had significantly
      higher thresholds compared with the paclitaxel group, but these values were still
      significantly lower than that of the controls. Control and control + CQ10 rats
      had similar threshold values during the protocol. CONCLUSION: The CQ10 treatment
      decreased the degree of paclitaxel-induced peripheral neuropathy in rats.

PMID- 23545609
TI  - Role of 17-beta estradiol in baroreflex sensitivity in the nucleus tractus
      solitarii via the autonomic system in ovariectomized rats.
AB  - OBJECTIVE: To investigate the effect of estrogen exerted through the autonomic
      system in the nucleus tractus solitarii (NTS) on increasing the sensitivity of
      the baroreflex under conditions of acute hypertension in ovariectomized rats.
      METHODS: In this experimental study, conducted in Kerman University of Medical
      Sciences, Kerman, Iran from March 2010 to October 2010, 36 female rats were
      ovariectomized and then estrogen capsules were implanted beneath their skin.
      After 2 weeks, the left femoral vein and artery were cannulated for phenylephrine
      infusion and recording of mean arterial pressure and heart rate. Subsequently,
      atropine, propranolol, and saline were injected into the NTS, followed by
      measurements of changes in heart rate and changes in mean arterial pressure just
      prior to phenylephrine infusion. RESULTS: Estrogen increased the bradycardia
      response and inhibited the rise of mean arterial pressure; namely, after
      phenylephrine infusion, the change in heart rate was significantly lower in the
      estrogen-receiving group compared with the control group (p<0.05). Baroreflex
      sensitivity was significantly increased in the estrogen-receiving group compared
      with the control group (p<0.01). Baroreflex sensitivity was significantly
      attenuated in both groups (estrogen-receiving and control) after atropine
      injection, compared with after propranolol or saline injection (p<0.01).
      CONCLUSION: It is probable that under conditions of acute hypertension, estrogen
      affects the NTS through the parasympathetic system and enhances baroreflex
      sensitivity.

PMID- 23545611
TI  - Study on serum zinc and selenium levels in epileptic patients.
AB  - OBJECTIVE: To estimate serum zinc and selenium levels in a group of healthy
      subjects and correlate these with epileptic patients. METHODS: This case-control
      study was conducted in the Department of Neurology, Valiasr Hospital, Iran,
      between November 2011 and May 2012 on 40 patients aged 26.63+/-5.78 years who
      were diagnosed with generalized and a single epileptic form of epilepsy by a
      neurologist for the first time. The control group was selected from healthy
      individuals, and matched to the case group. Serum zinc was measured by the
      calorimetric method using a Randox kit. Selenium was measured by atomic
      absorption spectroscopy. RESULTS: The mean zinc level was 151.2+/-29.75 ug/dl in
      the cases, and 181.63+/-60.19 ug/dl in the controls (p=0.006). The mean selenium
      level was 73.37+/-13.31 ug/l in cases compared with 85.55+/-19.39 ug/dl in
      controls (p=0.002). We also found a significant difference between the selenium
      levels by gender in the 2 groups (p=0.03). CONCLUSION: We observed statistically
      significant changes in serum zinc and selenium levels of epileptic adult patients
      in comparison with the control group. As zinc and selenium are used as potent
      antioxidants in cellular interactions, changes in their serum values may result
      in enzymatic changes, which in turn can cause neurological disorders.

PMID- 23545612
TI  - Ineffectiveness of topiramate and levetiracetam in infantile spasms non
      responsive to steroids. Open labeled randomized prospective study.
AB  - OBJECTIVE: To compare the effectiveness of 2 novel antiepileptic drugs,
      topiramate and levetiracetam, as a second line treatment for infantile spasm when
      oral steroids fail. METHODS: Forty infants under 2 years with clinically- and EEG
      proven infantile spasms that did not respond to prednisone (2mg/kg/day in 2
      divided doses) were recruited and randomized into 2 groups. They were randomly
      assigned to either topiramate (group 1; 1mg/kg/day for 3 days then increased by
      1mg/kg/day every third day up to 6mg/kg/day) or levetiracetam (group 2;
      10mg/kg/day for 5 days and then increased by 10mg/kg/day every 5 days up to
      60mg/kg/day). The study was conducted in the Pediatric Neurology Department at
      the National Neuroscience Institute of King Fahad Medical City, Riyadh, Kingdom
      of Saudi Arabia between January 2008 and December 2010. RESULTS: Of the 20
      patients included in the final data analysis, 11 (55%) were administered
      topiramate and 9 (45%) levetiracetam. Eighteen patients did not respond to the
      first drug, and subsequently to the other drug when crossed-over. Two patients
      with infantile spasm responded to either one drug without crossover. Their EEGs
      improved with time. CONCLUSION: The present study demonstrated the
      ineffectiveness of topiramate and levetiracetam suggesting current treatment
      modalities are grossly inadequate underscoring the urgent need for more research
      efforts to overcome current deficiencies. Two patients with cryptogenic infantile
      spasm responded to treatment suggesting the potential for treatment of such
      patients with these 2 drugs, and merits further multicenter investigation.

PMID- 23545613
TI  - The relationship between mean platelet volume and severity of acute ischemic
      brain stroke.
AB  - OBJECTIVE: To determine whether an association exists between mean platelet
      volume (MPV) and severity of acute ischemic stroke. Also, to investigate the
      power of MPV for discriminating more severe ischemic stroke from mild events.
      METHODS: We divided 100 patients with first ischemic stroke presenting to the
      Neurology Department, Fatemieh Hospital, Semnan, Iran between January 2010 and
      January 2011 into 2 groups based on Rankin score (group 1: score 0-2, and group
      2: score 3 or more). Blood samples were taken to measure MPV. Severity of
      ischemic stroke was assessed by the Modified Rankin scale. RESULTS: The MPV value
      was higher and more significant in group 2 than group 1 (9.36+/-0.95 versus
      8.55+/-0.65, p<0.001). Also, the mean platelet count was significantly lower in
      group 2 (238.8+/-89.2 versus 283.7+/-59.2, p=0.020). After controlling for the
      risk profile associated with ischemic stroke in the multivariate logistic
      regression model, the effect of MPV in ischemic stroke remained statistically
      significant (p=0.012). The area under the ROC curve was 0.77, indicating the high
      discriminative value of MPV for predicting severe ischemic stroke based on Rankin
      score >/= 3 from mild stroke. CONCLUSION: The MPV is associated with ischemic
      stroke severity and has a high value for discriminating severe from mild ischemic
      stroke.

PMID- 23545614
TI  - Management options of chronic low back pain. A randomized blinded clinical trial.
AB  - OBJECTIVE: To compare efficacies of 2 active programs in the management of
      chronic low back pain (CLBP). METHODS: This prospective, stratified, randomized
      single-blinded controlled study was conducted in the Department of Rehabilitation
      Medicine, King Abdullah University Hospital, Irbid, Jordan, between February and
      December 2010. A total of 100 patients were randomized to either 6-weeks of
      multidisciplinary rehabilitation (group A) or therapist-assisted exercise (group
      B). At baseline and 6 weeks, the visual analogue scale (VAS) pain score was
      estimated, as a primary outcome measure. McGill pain score, Oswestry Disability
      Index (ODI), trunk forward flexion and extension, left and right lateral bending,
      were applied before and after treatment and were employed as secondary outcome
      measures. RESULTS: All outcome measures significantly improved in group A after
      treatment, compared with group B. The VAS, McGill, ODI scores, left and right
      lateral bending decreased significantly, whereas forward and backward bending
      increased. A significant number of patients returned to work in group A at the
      end of 6 weeks, compared with group B. These effects were maintained over 12 and
      24 weeks of follow-up. CONCLUSION: Multidisciplinary rehabilitation improved
      functional indices and pain scale scores in group A compared with B. This would
      be an effective strategy in CLBP management.

PMID- 23545615
TI  - Primary antiphospholipid syndrome manifesting as partial status epilepticus.
AB  - Primary antiphospholipid syndrome (APS) is an autoimmune disease defined by
      vascular thrombosis, pregnancy complications, and persistent antiphospholipid
      antibodies. Neurological manifestations include stroke, seizures, and chorea
      among others. Seizures are often precipitated by an acute ischemic event, but
      occasionally, structural abnormalities are absent. We present a 61-year-old man
      who developed partial seizures that progressed into partial status epilepticus.
      His seizures were intractable and required aggressive treatment with multiple
      anti-epileptic medications. He was diagnosed with primary APS and treated with
      anticoagulation. Head imaging did not reveal any acute ischemic events. This case
      demonstrates that primary APS may present as a refractory status epilepticus
      unrelated to acute cerebral ischemia.

PMID- 23545616
TI  - Hypertensive encephalopathy as the initial manifestation of Guillain-Barre
      syndrome in a 7-year-old girl.
AB  - We report a case involving a 7-year-old girl who initially presented with seizure
      and hypertensive encephalopathy, serious autonomic manifestations associated with
      Guillain-Barre syndrome, followed by subsequent bilateral ascending flaccid
      paralysis. Cerebrospinal fluid analysis showed cytoalbuminous dissociation. Nerve
      conduction velocity tests showed features of demyelinating
      polyradiculoneuropathy. An immunofluorescence test of her serum was positive for
      mycoplasma immunoglobulin M antibody. The present case highlights the importance
      of considering the initial autonomic manifestations of Guillain-Barre syndrome in
      the differential diagnosis of unexplained acute hypertensive crisis.

PMID- 23545617
TI  - Co-morbid Guillain-Barre syndrome and acute disseminated encephalomyelitis.
AB  - Guillain-Barre syndrome (GBS) and acute disseminated encephalomyelitis (ADEM) are
      clinically distinct demyelinating disorders that share an autoimmune pathogenesis
      and prior history of viral infection or vaccination. Concurrent GBS and ADEM are
      uncommon with few reported cases. Our patient is a 10-year-old girl who presented
      with acute quadriparesis, areflexia, and urinary retention. Lumber puncture
      revealed mild pleocytosis and elevated protein. She required mechanical
      ventilation and failed to improve after intravenous immunoglobulins. She
      subsequently developed double vision and disturbed level of consciousness. Brain
      MRI revealed multiple white matter lesions suggestive of ADEM. Based on the
      temporal association and exclusion of alternative etiologies, we made a diagnosis
      of GBS and ADEM. She improved remarkably after intravenous methylprednisolone. We
      conclude that co-morbid GBS and ADEM is an uncommon entity presenting with severe
      neurological morbidity. Prompt recognition and treatment can hasten the recovery
      and therefore improve the neurological outcome.

PMID- 23545618
TI  - Clinical presentation and differential diagnosis of Lambert-Eaton myasthenic
      syndrome.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is frequently associated with
      malignancy, especially small cell lung cancer (SCLC). Here, we describe a patient
      with a 5-year history of cervical myelopathy who presented with recurrent limb
      weakness of her limbs and complained of recent progressive weakness. Following an
      examination that included electromyography, a chest CT scan, and a
      bronchofiberscopy examination with brushing biopsy, the patient was diagnosed
      with LEMS and SCLC. This case report highlights the ongoing need for clinicians
      to be observant for cases of LEMS, to consider both patient history and physical
      examination data, and to accurately obtain a differential diagnosis between LEMS
      and other diseases, which also cause weakness.

PMID- 23545619
TI  - Obstructive hydrocephalus caused by giant basilar artery aneurysm.
AB  - Giant basilar artery aneurysms are rarely associated with hydrocephalus. When it
      occurs the treatment usually addresses the hydrocephalus rather than the aneurysm
      itself, especially if it is already thrombosed. The treatment options include
      ventriculoperitoneal shunting and endoscopic third ventriculostomy, which may be
      related to high complication rates. However, reducing the intracranial
      hypertension may produce aneurysmal growth. We report a patient with obstructive
      hydrocephalus due to thrombosed giant basilar artery aneurysm. The patient
      initially presented with symptoms of increased intracranial pressure, and was
      managed by ventriculoperitoneal shunting with significant symptomatic
      improvement. Fifteen days after operation, the patient died due to a
      cerebrovascular event. We report a case that deteriorated because of cerebral
      infarction due to aneurysmal growth after ventriculoperitoneal shunting. We also
      discuss the treatment options in such cases.

PMID- 23545620
TI  - Diagnostic uncertainty of tumefactive cystic demyelinating lesions.

PMID- 23545621
TI  - Generalized anhidrosis.

PMID- 23545622
TI  - Radiological predictors of neurological compromise in adults with filum terminale
      lipoma.

PMID- 23545623
TI  - Depression and anxiety in parents of children with epilepsy. Are fathers
      involved?

PMID- 23545624
TI  - Platelet alloantigen polymorphism and migraine headaches.

PMID- 23545625
TI  - Intracranial hydatid cyst. Clinical features and outcomes of surgical treatment
      of a series of 8 Iraqi cases.

PMID- 23545626
TI  - Mechanically resilient electrospun TiC nanofibrous mats surface-decorated with Pt
      nanoparticles for oxygen reduction reaction with enhanced electrocatalytic
      activities.
AB  - Mechanically resilient mats consisting of overlaid electrospun nanofibers with
      self-generated TiC crystallites embedded in a carbon matrix are surface-decorated
      with Pt nanoparticles as a novel electrocatalytic system for oxygen reduction
      reaction. Electrocatalytic activities (e.g., on-set potential and current
      density) of Pt are substantially enhanced due to high specific surface area of
      the support and the synergetic effect of TiC and Pt on electrocatalysis.

PMID- 23545628
TI  - Bilateral nerve sparing robotic-assisted radical prostatectomy is associated with
      faster continence recovery but not with erectile function recovery compared with
      retropubic open prostatectomy: the need for accurate selection of patients.
AB  - Robotic-assisted radical prostatectomy (RARP) shows measurable advantages,
      compared to conventional open surgery, even if some aspects are, still, under
      debate. The aim of this study was to compare the potency recovery rate of
      patients with clinically localised prostate cancer treated by bilateral nerve
      sparing (BNS) RARP or retropubic radical prostatectomy (RRP), and secondarily,
      the urinary continence recovery evaluation and the oncological efficacy. All
      patients treated with BNS-RARP or BNS-RRP for clinically localised prostate
      cancer, performed by a single dedicated surgeon, between January 2004 and
      December 2008, were enrolled in this non-randomised prospective comparative
      study. The International Index of Erectile Function (IIEF) and erection hardness
      score (EHS), in the form of a questionnaire, were self-administered to each
      patient pre-operatively and after 12 months. The presence of surgical margins was
      considered as oncological outcome measure. Eighty-two patients underwent BNS-RARP
      while 48 underwent BNS-RRP. For BNS-RARP and BNS-RRP the median operative time
      was 221 and 103 min, respectively (P<0.001; df=128; t=721.43),and intra-operative
      blood loss was 280 and 565 ml, respectively (P<0.001; df=128; t=1742.44). At a
      mean follow-up period of 12.4+/-2.3 months, 12 patients (25%) in the BNS-RRP
      group and 22 (26.8%) in the BNS-RARP group were considered potent with or without
      drugs (P=0.81). Moreover, we did not find any statistically significant
      difference between the 2 groups in terms of IEFF and EHS scores after treatment
      (17.21 vs. 16.98; P=0.16 and 2.1 vs. 2.0; P=0.54). On the other hand,
      statistically significant differences between the 2 groups were found in terms of
      faster urinary continence recovery and the presence of positive surgical margins
      (P<0.001, P=0.009). Shorter catheterization duration (7 vs. 3 days) and post
      operative hospital stays (8 vs. 4 days; P<0.001) were found in the BNS-RARP group
      compared to the BNS-RRP group. In conclusion, our results demonstrate that BNS
      RARP does not improve erectile function recovery compared to open radical
      prostatectomy; however, it significantly improves urinary continence and
      decreases the presence of positive surgical margins.

PMID- 23545629
TI  - Genotype analysis of the NRF2 gene mutation in lung cancer.
AB  - Nuclear factor (erythroid derived 2)-like 2 (NRF2, gene name NFE2L2) gene
      mutations have been previously identified in lung cancers. The constitutive
      activation of NRF2 resulting from gene mutations has been correlated with the
      poor prognosis of patients with squamous cell lung cancer. However, DNA
      sequencing using PCR methods described to date is time-consuming and requires
      significant quantities of DNA. Thus, this existing approach is not suitable for a
      routine pre-therapeutic screening program. We genotyped the NRF2 gene mutation
      status in 262 surgically treated lung cancer cases using LightCycler analysis.
      The presence of the NRF2 gene mutation was confirmed by direct sequencing. We
      detected 6 cases (2.3%) with NRF2 gene mutations in our cohort, particularly
      smokers (P=0.04) with squamous histology (P=0.0001). NRF2 gene mutations were
      present in 10% (6/60) of the lung squamous cell carcinoma (SqCC) cases. The NRF2
      gene mutation was exclusive of epidermal growth factor receptor mutations. The
      NRF2 gene mutation occurred with a tendency towards a higher frequency in male
      patients. Patients with the NRF2 gene mutation (n=22, 11 succumbed to disease)
      had a significantly worse prognosis when compared with the patients with the wild
      type NRF2 gene (n=521, 98 succumbed to disease) from a larger cohort study (log
      rank test, P<0.0001) even upon multivariate analysis. In our study, NRF2 gene
      mutations played a role in the prognosis of patients with SqCC of the lung.

PMID- 23545633
TI  - The role of palliative care in patients with neurological diseases.
AB  - Palliative care aims to improve the quality of life of patients and their
      families affected by life-threatening illness. This approach applies to a large
      and growing proportion of neurological disorders, most prominently stroke and
      dementia. Challenges in the palliative care of patients with incurable
      neurological diseases include the broad spectrum of the rate of symptom
      progression, a lack of reliable prognostic markers, scarcity of evidence for
      efficacy of symptomatic treatments, and a high prevalence of difficulties with
      communication, cognitive impairment and behavioural disturbances. A genuinely
      multidisciplinary approach to neurological palliative care is, therefore,
      required. However, palliative care is not an integral part of neurological
      training in most countries. This Perspectives article aims to underscore the
      importance of integrating palliative care into daily clinical practice. The basic
      principles and challenges of neurological palliative care are also outlined in
      the light of relevant literature.

PMID- 23545635
TI  - Structure of the hypothetical DUF1811-family protein GK0453 from Geobacillus
      kaustophilus HTA426.
AB  - The crystal structure of a conserved hypothetical protein, GK0453, from
      Geobacillus kaustophilus has been determined to 2.2 A resolution. The crystal
      belonged to space group P4(3)2(1)2, with unit-cell parameters a = b = 75.69, c =
      64.18 A. The structure was determined by the molecular-replacement method and was
      refined to a final R factor of 22.6% (R(free) = 26.3%). Based on structural
      homology, the GK0453 protein possesses two independent binding sites and hence it
      may simultaneously interact with two proteins or with a protein and a nucleic
      acid.

PMID- 23545636
TI  - Organophosphorus acid anhydrolase from Alteromonas macleodii: structural study
      and functional relationship to prolidases.
AB  - The bacterial enzyme organophosphorus acid anhydrolase (OPAA) is able to catalyze
      the hydrolysis of both proline dipeptides (Xaa-Pro) and several types of
      organophosphate (OP) compounds. The full three-dimensional structure of the
      manganese-dependent OPAA enzyme is presented for the first time. This enzyme,
      which was originally isolated from the marine bacterium Alteromonas macleodii,
      was prepared recombinantly in Escherichia coli. The crystal structure was
      determined at 1.8 A resolution in space group C2, with unit-cell parameters a =
      133.8, b = 49.2, c = 97.3 A, beta = 125.0 degrees . The enzyme forms dimers and
      their existence in solution was confirmed by dynamic light scattering and size
      exclusion chromatography. The enzyme shares the pita-bread fold of its C-terminal
      domain with related prolidases. The binuclear manganese centre is located in the
      active site within the pita-bread domain. Moreover, an Ni(2+) ion from
      purification was localized according to anomalous signal. This study presents the
      full structure of this enzyme with complete surroundings of the active site and
      provides a critical analysis of its relationship to prolidases.

PMID- 23545637
TI  - Crystallization and X-ray structure determination of a thermoalkalophilic lipase
      from Geobacillus SBS-4S.
AB  - A thermoalkalophilic lipase (LIPSBS) from the newly isolated Geobacillus strain
      SBS-4S which hydrolyzes a wide range of fatty acids has been characterized. In
      the present study, the crystallization of purified LIPSBS using the sitting-drop
      vapour-diffusion method and its X-ray diffraction studies are described. The
      crystals belonged to the orthorhombic space group P212121, with unit-cell
      parameters a = 55.13, b = 71.75, c = 126.26 A. The structure was determined at
      1.6 A resolution by the molecular-replacement method using the lipase from G.
      stearothermophilus L1 as a model.

PMID- 23545638
TI  - Structure of glutaminyl cyclase from Drosophila melanogaster in space group I4.
AB  - The structure of ligand-free glutaminyl cyclase (QC) from Drosophila melanogaster
      (DmQC) has been determined in a novel crystal form. The protein crystallized in
      space group I4, with unit-cell parameters a = b = 122.3, c = 72.7 A. The crystal
      diffracted to a resolution of 2 A at the home source. The structure was solved by
      molecular replacement and was refined to an R factor of 0.169. DmQC exhibits a
      typical alpha/beta-hydrolase fold. The electron density of three monosaccharides
      could be localized. The accessibility of the active site will facilitate
      structural studies of novel inhibitor-binding modes.

PMID- 23545640
TI  - Investigating the active centre of the Scytalidium thermophilum catalase.
AB  - Almost all monofunctional haem catalases contain a highly conserved core
      containing the active site, which is connected to the exterior of the enzyme by
      three channels. These channels have been identified as potential routes for
      substrate flow and product release. To further investigate the role of these
      molecular channels, a series of mutants of Scytalidium thermophilum catalase were
      generated. The three-dimensional structures of four catalase variants, N155A,
      V123A, V123C and V123T, have been determined at resolutions of 2.25, 1.93, 1.9
      and 1.7 A, respectively. The V123C variant contains a new covalent bond between
      the S atom of Cys123 and the imidazole ring of the essential His82. This variant
      enzyme has only residual catalase activity and contains haem b instead of the
      normal haem d. The H82A variant demonstrates low catalase and phenol oxidase
      activities (0.2 and 20% of those of recombinant wild-type catalase-phenol
      oxidase, respectively). The N155A and N155H variants exhibit 4.5 and 3% of the
      wild-type catalase activity and contain haem d, showing that Asn155 is essential
      for catalysis but is not required for the conversion of haem b to haem d.
      Structural analysis suggests that the cause of the effect of these mutations on
      catalysis is the disruption of the ability of dioxygen substrates to efficiently
      access the active site. Additional mutants have been characterized biochemically
      to further probe the roles of the different channels. Introducing smaller or
      polar side chains in place of Val123 reduces the catalase activity. The F160V,
      F161V and F168V mutants show a marked decrease in catalase activity but have a
      much lower effect on the phenol oxidase activity, despite containing
      substoichiometric amounts of haem.

PMID- 23545639
TI  - Structure of Neisseria meningitidis lipoprotein GNA1162.
AB  - GNA1162, a predicted lipoprotein from Neisseria meningitidis, is a potential
      candidate for a universal vaccine against meningococcal disease caused by N.
      meningitidis serogroup B. Here, the crystal structure of GNA1162 at 1.89 A
      resolution determined by single-wavelength anomalous dispersion (SAD) is
      reported. The structure of GNA1162 appears to be a dimer in the crystallographic
      asymmetric unit as well as in solution. The overall structure of the dimer
      indicates that each monomer inserts its C-terminal alpha5 helix into the
      hydrophobic groove of the other molecule. Moreover, the beta4 strands of each
      monomer lie antiparallel to each other and interact through multiple main-chain
      hydrogen bonds. Through structural comparisons and operon predictions, it is
      hypothesized that GNA1162 is part of a transport system and assists in transport
      and reassembly. The crystal structure of GNA1162 sheds light on its possible
      function and provides potentially valuable information for the design of a
      vaccine against meningococcal disease.

PMID- 23545641
TI  - The 1.58 A resolution structure of the DNA-binding domain of bacteriophage SF6
      small terminase provides new hints on DNA binding.
AB  - DNA packaging in tailed bacteriophages and in evolutionarily related
      herpesviruses is controlled by a viral-encoded terminase. As in a number of other
      phages, in the Bacillus subtilis bacteriophages SF6 and SPP1 the terminase
      complex consists of two proteins: G1P and G2P. The crystal structure of the N
      terminal DNA-binding domain of the bacteriophage SF6 small terminase subunit G1P
      is reported. Structural comparison with other DNA-binding proteins allows a
      general model for the interaction of G1P with the packaging-initiation site to be
      proposed.

PMID- 23545643
TI  - Structure of PCNA from Drosophila melanogaster.
AB  - Proliferating cell nuclear antigen (PCNA) plays essential roles in DNA
      replication, DNA repair, cell-cycle regulation and chromatin metabolism. The PCNA
      from Drosophila melanogaster (DmPCNA) was purified and crystallized. The crystal
      of DmPCNA diffracted to 2.0 A resolution and belonged to space group H3, with
      unit-cell parameters a = b = 151.16, c = 38.28 A. The structure of DmPCNA was
      determined by molecular replacement. DmPCNA forms a symmetric homotrimer in a
      head-to-tail manner. An interdomain connector loop (IDCL) links the N- and C
      terminal domains. Additionally, the N-terminal and C-terminal domains contact
      each other through hydrophobic associations. Compared with human PCNA, the IDCL
      of DmPCNA has conformational changes, which may explain their difference in
      function. This work provides a structural basis for further functional and
      evolutionary studies of PCNA.

PMID- 23545642
TI  - Structure of a filament of stacked octamers of human DMC1 recombinase.
AB  - Eukaryal DMC1 proteins play a central role in homologous recombination in meiosis
      by assembling at the sites of programmed DNA double-strand breaks and carrying
      out a search for allelic DNA sequences located on homologous chromatids. They are
      close homologs of eukaryal Rad51 and archaeal RadA proteins and are remote
      homologs of bacterial RecA proteins. These recombinases (also called DNA strand
      exchange proteins) promote a pivotal strand-exchange reaction between homologous
      single-stranded and double-stranded DNA substrates. An octameric form of a
      truncated human DMC1 devoid of its small N-terminal domain (residues 1-83) has
      been crystallized. The structure of the truncated DMC1 octamer is similar to that
      of the previously reported full-length DMC1 octamer, which has disordered N
      terminal domains. In each protomer, only the ATP cap regions (Asp317-Glu323) show
      a noticeable conformational difference. The truncated DMC1 octamers further stack
      with alternate polarity into a filament. Similar filamentous assemblies of DMC1
      have been observed to form on DNA by electron microscopy.

PMID- 23545644
TI  - Deer mouse hemoglobin exhibits a lowered oxygen affinity owing to mobility of the
      E helix.
AB  - The deer mouse, Peromyscus maniculatus, exhibits altitude-associated variation in
      hemoglobin oxygen affinity. To examine the structural basis of this functional
      variation, the structure of the hemoglobin was solved. Recombinant hemoglobin was
      expressed in Escherichia coli and was purified by ion-exchange chromatography.
      Recombinant hemoglobin was crystallized by the hanging-drop vapor-diffusion
      method using polyethylene glycol as a precipitant. The obtained orthorhombic
      crystal contained two subunits in the asymmetric unit. The refined structure was
      interpreted as the aquo-met form. Structural comparisons were performed among
      hemoglobins from deer mouse, house mouse and human. In contrast to human
      hemoglobin, deer mouse hemoglobin lacks the hydrogen bond between alpha1Trp14 in
      the A helix and alpha1Thr67 in the E helix owing to the Thr67Ala substitution. In
      addition, deer mouse hemoglobin has a unique hydrogen bond at the alpha1beta1
      interface between residues alpha1Cys34 and beta1Ser128.

PMID- 23545645
TI  - Structure of an atypical FeoB G-domain reveals a putative domain-swapped dimer.
AB  - FeoB is a transmembrane protein involved in ferrous iron uptake in prokaryotic
      organisms. FeoB comprises a cytoplasmic soluble domain termed NFeoB and a C
      terminal polytopic transmembrane domain. Recent structures of NFeoB have revealed
      two structural subdomains: a canonical GTPase domain and a five-helix helical
      domain. The GTPase domain hydrolyses GTP to GDP through a well characterized
      mechanism, a process which is required for Fe(2+) transport. In contrast, the
      precise role of the helical domain has not yet been fully determined. Here, the
      structure of the cytoplasmic domain of FeoB from Gallionella capsiferriformans is
      reported. Unlike recent structures of NFeoB, the G. capsiferriformans NFeoB
      structure is highly unusual in that it does not contain a helical domain. The
      crystal structures of both apo and GDP-bound protein forms a domain-swapped
      dimer.

PMID- 23545646
TI  - Overexpression, crystallization and preliminary X-ray crystallographic analysis
      of hypothetical protein SAV0479 from Staphylococcus aureus Mu50.
AB  - SAV0479, a hypothetical protein from the Mu50 strain of methicillin- and
      vancomycin-resistant Staphylococcus aureus, was selected for structure and
      function determination as part of a structural genomics project. Here, the
      cloning, overexpression, purification and crystallization of SAV0479 are
      reported. Crystals were obtained by the hanging-drop vapour-diffusion method and
      diffraction data were collected to a resolution of 2.8 A. The crystals belonged
      to space group P3(1)21, with unit-cell parameters a = b = 81.48, c = 82.53 A.
      Three monomers of SAV0479 are present in each asymmetric unit.

PMID- 23545647
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of the mitochondrial tryparedoxin peroxidase from Leishmania
      braziliensis.
AB  - Tryparedoxin peroxidase (TXNPx) is an essential constituent of the main enzymatic
      scavenger system for reactive oxygen species (ROS) in trypanosomatids. Genetic
      studies have demonstrated the importance of this system for the development and
      virulence of these parasites, representing a potential target for the discovery
      of new trypanocidal drugs. In this work, the mitochondrial TXNPx from Leishmania
      braziliensis was cloned, overexpressed, purified and crystallized. The crystals
      diffracted to 3.3 A resolution and belonged to space group P4(2)2(1)2, with unit
      cell parameters a = b = 131.8, c = 44.4 A. These studies will contribute to a
      better understanding of the molecular mechanisms involved in ROS detoxification
      by trypanosomatids.

PMID- 23545648
TI  - Crystallization and preliminary crystallographic analysis of the first
      condensation domain of viomycin synthetase.
AB  - Nonribosomal peptide synthetases (NRPSs) are large multimodular enzymes that
      synthesize important secondary metabolites such as antibiotics. NRPSs follow a
      modular synthetic logic whereby each successive amino-acid monomer is added to
      the peptide chain by successive multi-domain modules. The condensation domain
      catalyzes the central chemical event in the synthetic cycle, peptide-bond
      formation, and is present in every elongation module of the NRPS. Viomycin is an
      antituberculosis nonribosomal peptide that is synthesized by a series of four
      NRPS proteins and then modified by tailoring proteins. In order to study the
      mechanisms of peptide-bond formation in viomycin and in NRPSs in general, a
      structural study of the first condensation domain of the viomycin synthetase
      protein VioA (VioA-C1) was initiated. The gene for VioA-C1 was cloned from
      genomic DNA of Streptomyces vinaceus, expressed as an octahistidine-tagged
      construct and purified by column chromatography. VioA-C1 was crystallized using
      the sitting-drop vapor-diffusion method. X-ray diffraction data were collected on
      a rotating-anode source to 2.9 A resolution. The data could be indexed in the
      orthorhombic space group P212121, with unit-cell parameters a = 46.165, b =
      68.335, c = 146.423 A. There is likely to be one monomer in the asymmetric unit,
      giving a solvent content of 49.2% and a Matthews coefficient (VM) of 2.42 A(3)
      Da(-1). Structural determination is in progress.

PMID- 23545649
TI  - Crystallization and preliminary crystallographic study of oligomers of the
      haemolytic lectin CEL-III from the sea cucumber Cucumaria echinata.
AB  - CEL-III is a Ca(2+)-dependent haemolytic lectin isolated from the marine
      invertebrate Cucumaria echinata. This lectin binds to Gal/GalNAc-containing
      carbohydrate chains on the cell surface and, after conformational changes,
      oligomerizes to form ion-permeable pores in cell membranes. CEL-III also forms
      soluble oligomers similar to those formed in cell membranes upon binding of
      specific carbohydrates in high-pH and high-salt solutions. These soluble and
      membrane CEL-III oligomers were crystallized and X-ray diffraction data were
      collected. Crystals of soluble oligomers and membrane oligomers diffracted X-rays
      to 3.3 and 4.2 A resolution, respectively, using synchrotron radiation and the
      former was found to belong to space group C2. Self-rotation functional analysis
      of the soluble oligomer crystal suggested that it might be composed of heptameric
      CEL-III.

PMID- 23545650
TI  - Purification, crystallization and preliminary crystallographic analysis of a 4
      thiouridine synthetase-RNA complex.
AB  - The sulfurtransferase 4-thiouridine synthetase (ThiI) is involved in the ATP
      dependent modification of U8 in tRNA. ThiI from Thermotoga maritima was cloned,
      overexpressed and purified. A complex comprising ThiI and a truncated tRNA was
      prepared and crystallized, and X-ray diffraction data were collected to a
      resolution of 3.5 A. The crystals belonged to the orthorhombic space group
      P212121, with unit-cell parameters a = 102.9, b = 112.8, c = 132.8 A.

PMID- 23545651
TI  - Crystallization and preliminary X-ray diffraction analysis of a DING protein from
      Pseudomonas aeruginosa PA14.
AB  - DING proteins form an emergent family of proteins consisting of an increasing
      number of homologues that have been identified in all kingdoms of life. They
      belong to the superfamily of phosphate-binding proteins and exhibit a high
      affinity for phosphate. In eukaryotes, DING proteins have been isolated by virtue
      of their implication in several diseases and biological processes. Some of them
      are potent inhibitors of HIV-1 replication/transcription, raising the question of
      their potential involvement in the human defence system. Recently, a protein from
      Pseudomonas aeruginosa strain PA14, named PA14DING or LapC, belonging to the DING
      family has been identified. The structure of PA14DING, combined with detailed
      biochemical characterization and comparative analysis with available DING protein
      structures, will be helpful in understanding the structural determinants
      implicated in the inhibition of HIV-1 by DING proteins. Here, the expression,
      purification and crystallization of PA14DING and the collection of X-ray data to
      1.9 A resolution are reported.

PMID- 23545652
TI  - Crystallization and preliminary crystallographic analysis of Axe2, an acetylxylan
      esterase from Geobacillus stearothermophilus.
AB  - Acetylxylan esterases are part of the hemi-cellulolytic system of many
      microorganisms which utilize plant biomass for growth. Xylans, which are
      polymeric sugars that constitute a significant part of the plant biomass, are
      usually substituted with acetyl side groups attached at position 2 or 3 of the
      xylose backbone units. Acetylxylan esterases hydrolyse the ester linkages of the
      xylan acetyl groups and thus improve the ability of main-chain hydrolysing
      enzymes to break down the sugar backbone units. As such, these enzymes play an
      important part in the hemi-cellulolytic utilization system of many microorganisms
      that use plant biomass for growth. Interest in the biochemical characterization
      and structural analysis of these enzymes stems from their numerous potential
      biotechnological applications. An acetylxylan esterase (Axe2) of this type from
      Geobacillus stearothermophilus T-6 has recently been cloned, overexpressed,
      purified, biochemically characterized and crystallized. One of the crystal forms
      obtained (RB1) belonged to the tetragonal space group I422, with unit-cell
      parameters a = b = 110.2, c = 213.1 A. A full diffraction data set was collected
      to 1.85 A resolution from flash-cooled crystals of the wild-type enzyme at 100 K
      using synchrotron radiation. A selenomethionine derivative of Axe2 has also been
      prepared and crystallized for single-wavelength anomalous diffraction
      experiments. The crystals of the selenomethionine-derivatized Axe2 appeared to be
      isomorphous to those of the wild-type enzyme and enabled the measurement of a
      full 1.85 A resolution diffraction data set at the selenium absorption edge and a
      full 1.70 A resolution data set at a remote wavelength. These data are currently
      being used for three-dimensional structure determination of the Axe2 protein.

PMID- 23545653
TI  - Crystallization and preliminary X-ray crystallographic studies of the CARD domain
      of human CARMA1.
AB  - The CARMA1 signalosome, which is composed of CARMA1 [caspase recruitment domain
      (CARD) containing MAGUK protein 1], BCL10 (B-cell lymphoma 10) and MALT1 (mucosa
      associated lymphoid tissue lymphoma translocation protein 1), is a molecular
      signalling complex that performs pivotal functions in T-cell receptor (TCR) and B
      cell receptor (BCR) mediated NF-kappaB activation. In this study, the CARD domain
      of human CARMA1 (CARMA1 CARD), corresponding to amino acids 14-109, was
      overexpressed in Escherichia coli using an engineered C-terminal His tag. CARMA1
      CARD was then purified to homogeneity and crystallized at 293 K. Finally, X-ray
      diffraction data were collected to a resolution of 3.2 A from a crystal belonging
      to space group P2(1)2(1)2(1) with unit-cell parameters a = 45.73, b = 53.37, c =
      91.89 A.

PMID- 23545654
TI  - Crystallization and preliminary X-ray diffraction analysis of the secreted
      protein Athe_0614 from Caldicellulosiruptor bescii.
AB  - The Athe_0614 protein is a component of the extracellular proteins secreted by
      the anaerobic, extremely thermophilic and cellulolytic bacterium
      Caldicellulosiruptor bescii. The recombinant protein was expressed in Escherichia
      coli, purified to near-homogeneity and crystallized using polyethylene glycol
      2000 monomethyl ether as a precipitant. The crystals belonged to the monoclinic
      space group P2(1), with unit-cell parameters a = 48.4, b = 42.2, c = 97.8 A, beta
      = 96.1 degrees , and diffracted to 2.7 A resolution using synchrotron radiation.

PMID- 23545655
TI  - Cloning, expression, purification, crystallization and preliminary
      crystallographic analysis of the N-terminal domain of serine glutamate repeat A
      (SgrA) protein from Enterococcus faecium.
AB  - Serine glutamate repeat A (SgrA) protein is an LPxTG surface adhesin of
      Enterococcus faecium and is the first bacterial nidogen-binding protein
      identified to date. It has been suggested that it binds to human nidogen, the
      extracellular matrix molecule of basal lamina, and plays a key role in the
      invasion and colonization of eukaryotic host cells. SgrA(28-288), having both a
      putative ligand-binding A domain and repetitive B domain, was expressed in
      Escherichia coli and purified using Ni-affinity and hydrophobic interaction
      chromatography. Further, the putative ligand-binding region, rSgrA(28-153), was
      subcloned, overexpressed and purified in both native and selenomethionine
      derivative forms. The native rSgrA(28-153) protein crystallized in the monoclinic
      space group P2(1) and diffracted to 3.3 A resolution using an in-house X-ray
      source, with unit-cell parameters a = 35.84, b = 56.35, c = 60.20 A, beta = 106.5
      degrees .

PMID- 23545656
TI  - Sample preparation, crystallization and structure solution of HisC from
      Mycobacterium tuberculosis.
AB  - Histidinolphosphate aminotransferase (HisC; Rv1600) from Mycobacterium
      tuberculosis was overexpressed in M. smegmatis and purified to homogeneity using
      nickel-nitrilotriacetic acid metal-affinity and gel-filtration chromatography.
      Diffraction-quality crystals suitable for X-ray analysis were grown by the
      hanging-drop vapour-diffusion technique using 30% polyethylene glycol monomethyl
      ether 2000 as the precipitant. The crystals belonged to the hexagonal space group
      P3221, with an unusual high solvent content of 74.5%. X-ray diffraction data were
      recorded to 3.08 A resolution from a single crystal using in-house Cu Kalpha
      radiation. The structure of HisC was solved by the molecular-replacement method
      using its Corynebacterium glutamicum counterpart as a search model. HisC is a
      dimer in the crystal as well as in solution.

PMID- 23545657
TI  - Preliminary crystallographic analysis of the kinase domain of SAD-1, a protein
      essential for presynaptic differentiation in Caenorhabditis elegans.
AB  - SAD-1 is a serine/threonine kinase which plays an important role in the
      regulation of both neuronal polarity and synapse formation in Caenorhabditis
      elegans. The kinase domain of SAD-1 from C. elegans was overexpressed in
      Escherichia coli BL21 (DE3) cells and purified to homogeneity using nickel
      nitrilotriacetic acid metal-affinity, ion-exchange and gel-filtration
      chromatography. Diffraction-quality crystals were grown using the sitting-drop
      vapour-diffusion technique from a condition consisting of 1 M CAPSO pH 9.6,
      10%(w/v) polyethylene glycol 3350. The crystals belonged to the monoclinic space
      group C2, with unit-cell parameters a = 205.4, b = 57.1, c = 71.7 A, beta = 106.1
      degrees . X-ray diffraction data were recorded to 3.0 A resolution from a single
      crystal using synchrotron radiation.

PMID- 23545658
TI  - Purification, crystallization and preliminary X-ray analysis of TP0435 (Tp17)
      from the syphilis spirochete Treponema pallidum.
AB  - Syphilis, caused by the bacterial spirochete Treponema pallidum, remains a
      prominent sexually transmitted infection worldwide. Despite sequencing of the
      genome of this obligate human pathogen 15 years ago, the functions of a large
      number of the gene products of T. pallidum are still unknown, particularly with
      respect to those of the organism's periplasmic lipoproteins. To better understand
      their functions, a structural biology approach has been pursued. To this end, the
      soluble portion of the T. pallidum TP0435 lipoprotein (also known as Tp17) was
      cloned, hyper-expressed in Escherichia coli and purified to apparent homogeneity.
      The protein crystals obtained from this preparation diffracted to 2.4 A
      resolution and had the symmetry of space group R3. In the hexagonal setting, the
      unit-cell parameters were a = b = 85.7, c = 85.4 A.

PMID- 23545659
TI  - Expression, purification, crystallization and preliminary X-ray analysis of
      tannase from Lactobacillus plantarum.
AB  - Tannase catalyses the hydrolysis of the galloyl ester bond of tannins to release
      gallic acid. It belongs to the serine esterases and has wide applications in the
      food, feed, beverage, pharmaceutical and chemical industries. The tannase from
      Lactobacillus plantarum was cloned, expressed and purified. The protein was
      crystallized by the sitting-drop vapour-diffusion method with microseeding. The
      crystals belonged to space group P1, with unit-cell parameters a = 46.5, b =
      62.8, c = 83.8 A, alpha = 70.4, beta = 86.0, gamma = 79.4 degrees . Although the
      enzyme exists mainly as a monomer in solution, it forms a dimer in the asymmetric
      unit of the crystal. The crystals diffracted to beyond 1.60 A resolution using
      synchrotron radiation and a complete data set was collected to 1.65 A resolution.

PMID- 23545660
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of the
      effector protein MoHrip1 from Magnaporthe oryzae.
AB  - The effector protein MoHrip1 from the pathogenic fungus Magnaporthe oryzae was
      purified and crystallized using the sitting-drop vapour-diffusion method. Native
      crystals appeared in a solution composed of 0.005 M cobalt(II) chloride
      hexahydrate, 0.005 M nickel(II) chloride hexahydrate, 0.005 M cadmium chloride
      hydrate, 0.005 M magnesium chloride hexahydrate, 0.1 M HEPES pH 7.5, 12%(w/v)
      polyethylene glycol 3350. A native data set was collected to 1.9 A resolution at
      100 K using an in-house X-ray source. The structure of MoHrip1 was successfully
      determined by molecular replacement using a homologous structure.

PMID- 23545661
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of
      effector protein MoHrip2 from Magnaporthe oryzae.
AB  - MoHrip2, a novel effector protein from the pathogenic fungus Magnaporthe oryzae,
      was purified and crystallized using the sitting-drop vapour-diffusion method.
      Native crystals and selenomethionine-labelled crystals were obtained using 2.2 M
      ammonium sulfate as a precipitant. A native data set was collected to 2.0 A
      resolution at 100 K using an in-house X-ray source and a selenomethionine
      labelled data set containing anomalous signal was collected to 1.8 A resolution
      at 100 K using a synchrotron source. Based on the anomalous signal generated from
      the Se atom, the MoHrip2 structure was successfully solved using the single
      wavelength anomalous dispersion (SAD) method.

PMID- 23545662
TI  - Crystallization and preliminary X-ray crystallographic studies of the coiled-coil
      domain of PIST.
AB  - PIST [PDZ (PSD-95, Discs-large and ZO-1) protein interacting specifically with
      TC10] functions as a regulator of membrane trafficking with Rab6A. Recently, the
      involvement of the fusion of PIST with ROS1 in cancer development has been
      identified. In this study, the coiled-coil domain of PIST, which is the domain
      responsible for interaction with Rab6A and fusion with ROS1, corresponding to
      amino acids 29-133, was overexpressed in Escherichia coli using engineered C
      terminal His tags. The coiled-coil domain of PIST was then purified to
      homogeneity and crystallized at 293 K. Finally, X-ray diffraction data were
      collected to a resolution of 4.0 A from a crystal belonging to the hexagonal
      space group P6(2)22 or P6(4)22, with unit-cell parameters a = b = 85.19, c =
      240.09 A, gamma = 120.00 degrees .

PMID- 23545663
TI  - Consideration of dual anti-platelet therapy duration after drug-eluting stent
      implantation in a Japanese population: a five-year follow-up after sirolimus
      eluting stent implantation.
AB  - OBJECTIVE: To investigate the risks and benefits of prolonged dual antiplatelet
      therapy (DAPT: thienopyridine plus aspirin) following placement of drug-eluting
      stents (DES). The optimal duration of DAPT is not well established. METHODS: We
      analyzed a prospective registry of 2,050 patients with sirolimus-eluting stents
      during a 5-year follow-up. We divided 1,691 patients into two groups according to
      DAPT duration (DAPT <=12 months (n=749) and DAPT >12 months (n=942)) and compared
      the clinical outcomes using a landmark analysis. RESULTS: The frequencies of
      major adverse cardiac events (MACE: 15.6% vs. 18.2%), death (10.0% vs. 11.5%),
      myocardial infarction (2.3% vs. 2.1%), target lesion revascularization (4.5% vs.
      6.3%) and stent thrombosis (0.8% vs. 0.8%) were similar between the two groups.
      However, the frequency of bleeding was higher in the DAPT >12 months group (1.1%
      vs. 2.6%, p=0.030). The adjusted 12-month landmark analysis showed no differences
      in the incidence of MACE (hazard ratio (HR) 0.892; 95% confidence interval (CI)
      0.689-1.155; p=0.385) or a composite of target vessel revascularization, cardiac
      death and myocardial infarction (target vessel failure: HR 0.922; 95% CI 0.678
      1.255; p=0.606). There were no differences in the frequency of stent thrombosis
      between the two groups during years 2 to 5 after stenting; however, with regard
      to bleeding, an increase in the frequency of hemorrhage events was observed after
      four years from the index procedures in the DAPT >12 months group. CONCLUSION:
      DAPT performed beyond 12 months is associated with increased an frequency of
      bleeding complications and does not prevent the incidence of MACE, including
      stent thrombosis, during five years of follow-up after sirolimus-eluting stent
      implantation. Conducting larger, randomized studies will therefore be needed to
      confirm this finding.

PMID- 23545664
TI  - Comparison of the efficacies of irbesartan and olmesartan after successful
      coronary stent implantation.
AB  - OBJECTIVE: We compared the efficacies of irbesartan and olmesartan after
      successful stent implantation in patients with stable angina. METHODS: Twenty-six
      patients were randomly divided into irbesartan and olmesartan groups and treated
      for approximately eight months (at follow-up coronary angiography). RESULTS:
      There were no differences in blood pressure (BP) reduction or late loss between
      the groups. The BP levels in both groups at follow-up were significantly reduced.
      The equality of variance of systolic (S)BP (i.e., the intragroup standard
      deviation of SBP) in the irbesartan group was significantly smaller than that
      observed in the olmesartan group at follow-up. In addition, log[pentraxin-3] was
      significantly decreased in all of the patients at follow-up, with no differences
      between the groups. Interestingly, the levels of log[high-sensitive C-reactive
      protein (hs-CRP)] measured at 0 weeks were positively associated with in-stent
      late loss, and among independent biochemical variables in addition to age,
      gender, body mass index and the kind of angiotensin receptor blockers at 0 weeks,
      only these levels were related to in-stent late loss, as assessed by a
      multivariate analysis. CONCLUSION: The ability of irbesartan to reduce BP is
      comparable to that of olmesartan, and irbesartan exhibits a lower variance of
      systolic BP after treatment. The level of log[hs-CRP] before stent implantation
      is a predictor of in-stent late loss.

PMID- 23545665
TI  - Metabolic syndrome is a poor predictor of diabetes in a Japanese health screening
      population.
AB  - OBJECTIVE: Although metabolic syndrome (MS) is considered to be a predictor of
      diabetes and cardiovascular disease, its value for predicting diabetes beyond the
      levels of fasting glucose (FG) and hemoglobin A1c (HbA1c) remains questionable.
      In this study, we evaluated the usefulness of MS and Japanese MS (JMS) as
      predictors of diabetes. METHODS: This study is a longitudinal study using data
      for 2,034 subjects who visited our Medical Check-up Center in both 2008 and 2011
      and were free from diabetes at baseline. The odds ratios (ORs) of developing
      diabetes in 2011 for MS and JMS were calculated after being adjusted for FG, age,
      sex and antihypertensive and antihyperlipidemic medication use, then further
      adjusted for HbA1c. The optimal cutoff points for FG, HbA1c and body mass index
      (BMI) to discriminate the development of diabetes and their
      sensitivities/specificities were obtained from receiver operating characteristic
      curves. These sensitivities/specificities were compared with the
      sensitivities/specificities of MS and JMS. RESULTS: The ORs (95% confidence
      intervals (CIs)) of developing diabetes for MS and JMS were 1.36 (0.57-3.23)
      (p=0.484) and 3.23 (1.25-8.36) (p=0.016), respectively, after being adjusted for
      FG and 1.06 (0.39-2.86) (p=0.915) and 2.34 (0.79-6.95) (p=0.126), respectively,
      after being further adjusted for HbA1c. The sensitivities/specificities of FG,
      HbA1c, BMI, MS and JMS were 0.625/0.897, 0.828/0/919, 0.625/0.734, 0.375/0.911,
      and 0.375/0.941, respectively. CONCLUSION: MS and JMS were found to be poor
      predictors of diabetes in a Japanese health screening population.

PMID- 23545666
TI  - Prognostic factors in 194 patients with chronic necrotizing pulmonary
      aspergillosis.
AB  - OBJECTIVE: The prognostic factors of chronic necrotizing pulmonary aspergillosis
      remain unclear. We assessed the prognostic factors of all-cause mortality in
      patients with chronic necrotizing pulmonary aspergillosis, focusing especially on
      underlying pulmonary disease, first-line treatment and host predisposition.
      METHODS: We retrospectively analyzed the medical records of 194 patients negative
      for HIV who had chronic necrotizing pulmonary aspergillosis treated at our
      institution in Saitama, Japan. RESULTS: The patients (median age, 68.5 years)
      were followed over a median follow-up time of 2.6 years. The underlying pulmonary
      diseases consisted of previous pulmonary tuberculosis in 59 (30.4%) patients,
      emphysema in 39 (20.1%) patients, interstitial lung disease in 32 (16.5%)
      patients, nontuberculous mycobacteriosis in 29 (14.9%) patients and other
      diseases in 35 (18%) patients. The first-line treatments included observation in
      65 (33.5%) patients, itraconazole in 56 (28.9%) patients, micafungin in 46
      (23.7%) patients, voriconazole in 22 (11.3%) patients and amphotericin B
      (including liposomal amphotericin B) in five (2.6%) patients. The overall
      cumulative mortality rate was 50.2% at five years and 67.4% at 10 years.
      Multivariate Cox proportional hazard modeling found an older age, the presence of
      systemic comorbidities, baseline corticosteroid use, a body mass index of <18.5
      kg/m(2) and a C-reactive protein level of >=5.0 mg/dL to be negative prognostic
      factors for all-cause mortality. CONCLUSION: The 5-year mortality rate of chronic
      necrotizing pulmonary aspergillosis was 50.2%. When clinical trials are designed
      and implemented to test effective drug therapies in patients with chronic
      necrotizing pulmonary aspergillosis, the trial patients should be stratified
      according to these prognostic factors prior to randomization.

PMID- 23545668
TI  - Evaluation of four hundred and forty seven brucellosis cases.
AB  - OBJECTIVE: Brucellosis remains as a widespread zoonosis, both worldwide and in
      our country that causes serious public health problems with the potential to
      create disease in humans and animals. The aim of the present study was to examine
      the characteristics of brucellosis patients followed in our clinic and to compare
      these cases with those reported in the literature. METHODS: Four hundred and
      forty-seven patients who were treated in our clinic between March 2004 and March
      2011 for a diagnosis of brucellosis and who were followed for one year after the
      completion of treatment were retrospectively examined. Data for the patients were
      obtained using brucellosis follow-up forms. RESULTS: Of the 447 patients, 261
      (58.4%) were women, and the mean age was 48+/-17 years. Focal organ involvement
      was detected in 178 (40%) cases, with the musculoskeletal system being the
      leading site (30.6%), followed by the central nervous system (5.4%).
      Spondylodiscitis exhibited a significant correlation with an advanced age, a high
      erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) level on
      admission (p=0.001, p=0.0001 and p=0.001, respectively). A significant
      correlation was found between sacroiliitis and a younger age (p=0.003). Relapse
      was observed in 35 (7.8%) cases. CONCLUSION: The present study allowed us to
      scrutinize the characteristics and complications of patients with brucellosis.
      Focal organ involvement of the musculoskeletal system was observed in the present
      cases, particularly spondylodiscitis and sacroiliitis. Spondylodiscitis was
      detected in elderly patients with high CRP and ESR values, whereas sacroiliitis
      was seen in younger patients. We believe that age, symptom duration and
      laboratory parameters should be evaluated in patients with brucellosis and that
      older patients in particular should be precisely examined for bone and joint
      complications.

PMID- 23545669
TI  - Use of patients' mobile phones to store and share personal health information:
      results of a questionnaire survey.
AB  - OBJECTIVE: To explore the opinions of outpatients concerning a new communication
      method: the self-management of assessed personal problems in health information
      records (SAPPHIRE) using patients' mobile phones to store and share medical
      content (medical SAPPHIRE, or m-SAPPHIRE). METHODS: A cross-sectional
      questionnaire survey. Patients Outpatients who visited us from March 1 to May 30,
      2012, were asked to complete a questionnaire survey regarding SAPPHIRE and m
      SAPPHIRE. The m-SAPPHIRE data consisted of a problem list, height, weight, waist
      size and active medication list. Ten questions were asked regarding the
      usefulness of m-SAPPHIRE, the sharing of m-SAPPHIRE and the use of mobile phones
      to store m-SAPPHIRE data. RESULTS: One hundred and ninety-three patients
      (male/female, 79/114; mean age, 57+/-21 years) were registered: 95.9% answered
      that m-SAPPHIRE would be useful, 98% agreed to manage their personal health
      records by themselves, and 95.8%, 93.8%, and 92.8% of the patients responded that
      they would allow m-SAPPHIRE information to be shared with family members, medical
      workers, and health care providers, respectively. Of the patients, 75.1%
      responded that they owned a mobile phone, and 43.5% answered that they could
      enter m-SAPPHIRE information into a mobile phone by themselves, while 27.5%
      responded that they could do so with someone's help. CONCLUSION: Patients believe
      that m-SAPPHIRE would be useful for retrieving their health records during
      emergency situations or for sharing with family members and medical and health
      care providers. SAPPHIRE using mobile phones could be an inexpensive and legal
      method for sharing medical data.

PMID- 23545667
TI  - Abacavir/lamivudine versus tenofovir/emtricitabine with atazanavir/ritonavir for
      treatment-naive Japanese patients with HIV-1 infection: a randomized multicenter
      trial.
AB  - OBJECTIVE: To compare the efficacy and safety of fixed-dose abacavir/lamivudine
      (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) with ritonavir-boosted atazanavir
      (ATV/r) in treatment-naive Japanese patients with HIV-1 infection. METHODS: A 96
      week multicenter, randomized, open-label, parallel group pilot study was
      conducted. The endpoints were times to virologic failure, safety event and
      regimen modification. RESULTS: 109 patients were enrolled and randomly allocated
      (54 patients received ABC/3TC and 55 patients received TDF/FTC). All randomized
      subjects were analyzed. The time to virologic failure was not significantly
      different between the two arms by 96 weeks (HR, 2.09; 95% CI, 0.72-6.13;
      p=0.178). Both regimens showed favorable viral efficacy, as in the intention-to
      treat population, 72.2% (ABC/3TC) and 78.2% (TDF/FTC) of the patients had an HIV
      1 viral load <50 copies/mL at 96 weeks. The time to the first grade 3 or 4
      adverse event and the time to the first regimen modification were not
      significantly different between the two arms (adverse event: HR 0.66; 95% CI,
      0.25-1.75, p=0.407) (regimen modification: HR 1.03; 95% CI, 0.33-3.19, p=0.964).
      Both regimens were also well-tolerated, as only 11.1% (ABC/3TC) and 10.9%
      (TDF/FTC) of the patients discontinued the allocated regimen by 96 weeks.
      Clinically suspected abacavir-associated hypersensitivity reactions occurred in
      only one (1.9%) patient in the ABC/3TC arm. CONCLUSION: Although insufficiently
      powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC,
      this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious
      initial regimen for HLA-B*5701-negative patients, such as the Japanese
      population.

PMID- 23545670
TI  - Gastric neuroendocrine carcinoma with non-islet cell tumor hypoglycemia
      associated with enhanced production of insulin-like growth factor II.
AB  - A 75-year-old man was admitted to the hospital with a loss of consciousness. His
      blood glucose level was 24 mg/dL. Abdominal computed tomography revealed multiple
      metastatic lesions in the liver, while upper endoscopy disclosed advanced gastric
      cancer. The hypoglycemia was refractory despite the administration of glucose and
      steroid therapy. The patient died within one month of admission. An autopsy
      revealed neuroendocrine-type gastric cancer, which, on examination with
      immunohistochemistry, was found to be negative for insulin and insulin-like
      growth factor I and positive for insulin-like growth factor II (IGF-II). The
      patient was diagnosed as having gastric cancer with non-islet cell tumor
      hypoglycemia (NICTH) caused by IGF-II.

PMID- 23545671
TI  - A rare case of propofol-induced liver injury during modified electroconvulsive
      therapy in an elderly woman.
AB  - A 75-year-old woman developed depression in 2010 and was treated with oral
      medications at our Department of Psychiatry. Since she showed no tendency toward
      improvement, she underwent modified electroconvulsive therapy (mECT). Later, she
      developed severe liver injury that was presumably induced by the propofol used
      for mECT. Propofol is an intravenous anesthetic agent that reportedly can be used
      relatively safely in the presence of liver dysfunction. We herein report the
      first case of propofol-induced liver injury definitively diagnosed based on
      positive drug lympocyte stimulation testing (DLST).

PMID- 23545672
TI  - Severe bradycardia caused by a single dose of lithium.
AB  - Lithium is used as a mood stabilizer in patients with manic-depressive disorder.
      It is a drug that requires close monitoring due to its narrow therapeutic window
      and many side effects. There are several case reports of lithium side effects and
      toxicity occurring even at the therapeutic levels. Cardiac toxicity is observed
      in approximately 5% of patients; however, severe bradycardia caused by a single
      dose of lithium is exceedingly rare. We herein report a case of severe
      symptomatic bradycardia in a young man that occurred after a single dose of
      lithium. This case emphasizes the need to closely monitor patients when
      initiating therapy, even before the lithium levels are high enough to be
      detected.

PMID- 23545673
TI  - Successful treatment of heart failure in an adult patient with Prader-Willi
      syndrome.
AB  - Prader-Willi Syndrome (PWS) is a rare genetic disorder characterized by physical,
      psychological and physiological abnormalities. Obesity and related cardiovascular
      diseases are a common problem in adult patients with PWS. This report describes a
      case of adult PWS with heart failure associated with marked obesity and sleep
      disordered breathing that was successfully treated with oxygen therapy, adaptive
      servoventilation, medications, diet therapy and rehabilitation.

PMID- 23545674
TI  - A mutant mRNA expression in an endomyocardial biopsy sample obtained from a
      patient with a cardiac variant of Fabry disease caused by a novel acceptor splice
      site mutation in the invariant AG of intron 5 of the alpha-galactosidase A gene.
AB  - We herein describe the case of a 58-year-old man who presented with dilated-phase
      hypertrophic cardiomyopathy (HCM) and required an implantable cardioverter
      defibrillator implant. Subsequently, the patient was diagnosed with Fabry disease
      (FD), which was suspected based on the results of an endomyocardial biopsy and
      diagnosed following demonstration of deficient alpha-galactosidase A (GLA)
      activity. Molecular studies showed a novel point mutation in the 3' splice site
      consensus sequence of intron 5 in the gene encoding GLA that created a new
      splicing site, resulting in the expression of mutant mRNA. FD should be
      considered a cause of HCM in patients with severe tachyarrhythmia without other
      remarkable manifestations of FD.

PMID- 23545676
TI  - Idiopathic orbital myositis associated with Graves' disease.
AB  - A 52-year-old man was referred to our clinic. One week before his visit, he had
      complained of left eye pain and double vision. His clinical features were
      exacerbated. Despite the acute onset, which is atypical of thyroid eye disease
      (TED), TED was suspected due to the patient's history of Graves' disease (GD).
      After conducting clinical examinations and orbital magnetic resonance imaging,
      the patient was diagnosed with idiopathic orbital myositis (IOM), and intravenous
      glucocorticoid therapy was administered. After treatment, the patient's clinical
      manifestations dramatically improved. This is a rare case in that the history of
      GD made it difficult to differentiate IOM from TED.

PMID- 23545675
TI  - Surgically proven normocalcemic primary hyperparathyroidism: speculation of the
      possible role of estrogen in the etiology of this disease in premenopausal women.
AB  - We herein report a rare case of surgically proven normocalcemic primary
      hyperparathyroidism (NCHPT). A premenopausal 51-year-old woman was referred to
      our clinic because parathyroid adenoma was detected on neck ultrasonography (US).
      The patient's serum calcium concentration was 9.3 mg/dL and the intact
      parathyroid hormone (PTH) level was 128.8 pg/mL. The findings of almost all other
      examinations were also compatible with a diagnosis of NCHPT. Then,
      parathyroidectomy was performed. The serum calcium and PTH concentrations reduced
      significantly but remained within the normal ranges. A histological examination
      demonstrated parathyroid adenoma. A review of this case and the associated
      literature suggests that estrogen plays a significant role in the etiology of
      NCHPT in premenopausal women.

PMID- 23545677
TI  - AA-amyloidosis in autosomal dominant polycystic kidney disease caused by chronic
      cyst infections lasting for 30 years.
AB  - We herein report the case of a 66-year-old Japanese woman who was admitted to our
      hospital due to diarrhea and malaise. She had been diagnosed with autosomal
      dominant polycystic kidney disease (ADPKD) at 35 years of age and had suffered
      from recurrent cyst infections since that time. Antibiotic therapy combined with
      hepatic cyst drainage and cyst sclerosing therapy led to transient improvements
      each time. At 66 years of age, watery diarrhea occurred. The patient's serum
      albumin level declined to 1.8 g/dL, and her C-reactive protein level was 4.5
      mg/dL. An endoscopic biopsy of the descending colon revealed amorphous deposits
      in the small arteries and tissues of the submucosal layer. The deposits were
      positive for Congo Red staining and amyloid A staining. Therefore, AA-amyloidosis
      was diagnosed. An endoscopic biopsy of the stomach and duodenum also showed AA
      amyloid deposits. If an ADPKD patient with a long history of cyst infection
      develops diarrhea and malaise, AA-amyloidosis should be considered as a possible
      complication.

PMID- 23545678
TI  - A bronchoesophageal fistula that developed shortly after the initiation of
      antituberculous chemotherapy.
AB  - A 26-year-old man visited our clinic because of a persistent cough. Although his
      chest roentgenography showed no abnormalities, a sputum culture revealed a
      positive result for Mycobacterium tuberculosis. Computed tomography (CT) prior to
      antituberculous chemotherapy demonstrated an esophagomediastinal fistula with
      subcarinal lymphadenopathy. One week after the treatment, he complained of a
      severe cough exacerbated by swallowing liquid. The development of a
      bronchoesophageal fistula (BEF) was suggested by esophagoscopy, and was confirmed
      by CT and bronchoscopy. The present case was unique because the process of BEF
      development could be followed by CT, and the BEF developed in an immunocompetent
      patient with relatively mild pulmonary tuberculosis.

PMID- 23545679
TI  - Tracheobronchial involvement in relapsing polychondritis diagnosed on
      endobronchial ultrasound.
AB  - Respiratory tract chondritis is not uncommon in patients with relapsing
      polychondritis (RP); however, diagnosing this condition remains problematic,
      especially in patients whose extrapulmonary manifestations do not predominate, as
      there are broad differential diagnoses of airway obstruction. We herein report
      the case of a 56-year-old man who presented with cough and dyspnea. Computed
      tomography of the chest demonstrated diffuse smooth thickening of the visualized
      tracheobronchial wall with a moderately narrowed lumen. Airway chondritis was
      diagnosed on endobronchial ultrasound following demonstration of thickening of
      the submucosal and cartilaginous layers in the anterior and lateral aspects of
      the bronchial wall, while the posterior region expressed less involvement. In
      conjunction with nasal and auricular chondritis, which were previously
      overlooked, RP was finally diagnosed.

PMID- 23545680
TI  - Acquired hemophilia associated with autoimmune bullous diseases: a report of two
      cases and a review of the literature.
AB  - Acquired hemophilia (AHA) is a relatively rare and life-threatening disease
      caused by autoantibodies against factor VIII. Autoimmune bullous diseases (ABD)
      are also caused by autoantibodies against specific skin proteins. We herein
      report two cases of AHA associated with ABD. These coincidences are extremely
      rare, and only 14 documented cases have been reported previously. We further
      analyzed the properties of the autoantibodies in our patients. The epitopes were
      the A2 domain in patient 1, and both the A2 domain and the light chain in patient
      2. Their isoforms were predominantly IgG4. Cross-reactivity could not be
      demonstrated. An accumulation of cases is required to unveil the pathogenesis of
      AHA.

PMID- 23545681
TI  - Cortical involvement in Marchiafava-Bignami disease can be a predictor of a poor
      prognosis: a case report and review of the literature.
AB  - Marchiafava-Bignami disease (MBD) is a rare alcohol-associated disorder
      characterized by demyelination and necrosis of the corpus callosum. We herein
      present the case of a 56-year-old man with chronic alcoholism who was admitted to
      our hospital in a coma without focal or lateralizing neurological signs. MRI
      revealed a callosal lesion consistent with MBD and additional bifrontal linear
      cortical lesions. The callosal lesion completely disappeared with intravenous
      administration of high-dose multivitamins and corticosteroids, although the
      patient remained in a vegetative state. This case further supports the notion
      that cortical involvement in patients with MBD is a predictor of a poor
      prognosis.

PMID- 23545682
TI  - Persistence of secondary restless legs syndrome in a phantom limb caused by end
      stage renal disease.
AB  - Our patient had secondary restless legs syndrome (RLS) in the left lower limb
      caused by end-stage renal disease (ESRD). Severe RLS symptoms persisted even
      after amputation of the affected limb. Considering that oral administration of a
      dopamine receptor agonist was effective in treating the RLS in the phantom limb
      in this case, dysfunction of the central dopaminergic system was thought to be
      involved in the phantom limb-RLS mechanism. The persistence of RLS symptoms even
      after amputation of the affected limb suggests that the area responsible for ESRD
      related RLS symptoms exists at the spinal level or in the higher central nervous
      system.

PMID- 23545683
TI  - Pulse-spray treatment of total occlusive jugular venous suppurative
      thrombophlebitis.
AB  - A 63-year-old man was diagnosed with jugular venous suppurative thrombophlebitis
      after undergoing strangulation ileus surgery. His condition was not stabilized by
      therapy with antibiotics, heparin or other supportive treatments. Pulse-spray
      treatment (PST) was administered, following which, the patient was afebrile
      without symptoms and the laboratory data improved. There were no complications
      such as sustained sepsis, septic embolisms or pulmonary embolisms. This is a
      unique case report of the use of a pulse-spray catheter in the treatment of total
      occlusive jugular venous suppurative thrombophlebitis following the failure of
      medical therapy.

PMID- 23545684
TI  - Rhabdomyolysis developing secondary to atorvastatin therapy in a patient with
      liver cirrhosis.
AB  - Atorvastatin is a lipid lowering agent that is widely used worldwide.
      Rhabdomyolysis is a rare but serious side effect that may lead to renal failure
      and dangerous electrolyte abnormalities in patients with decreased hepatic
      clearance of atorvastatin. We herein report the case of a patient with liver
      cirrhosis receiving atorvastatin therapy for ischemic heart disease and
      hyperlipidemia who developed rhabdomyolysis and acute renal failure.

PMID- 23545685
TI  - Intussusception caused by an ileocecal lymphoma disclosed on 18F-FDG-PET/CT.

PMID- 23545686
TI  - Multiple myeloma involving the extrahepatic bile duct.

PMID- 23545687
TI  - Ventricular tachycardia in a patient with Gorlin syndrome.

PMID- 23545688
TI  - Coronary tube detected on 64-multidetector row CT.

PMID- 23545689
TI  - Isolated pulmonary valve endocarditis detected on multislice CT.

PMID- 23545690
TI  - Acronecrosis with cold agglutinin disease mimics diabetic gangrene.

PMID- 23545691
TI  - Osteoma of the internal auditory canal.

PMID- 23545692
TI  - Tuberculous peritonitis incidentally diagnosed on FDG-PET/CT.

PMID- 23545693
TI  - Metronidazole-induced encephalopathy.

PMID- 23545694
TI  - Bilateral giant ovarian serous cystadenomas mimicking pregnancy.

PMID- 23545695
TI  - Jordanian mothers' beliefs about the causes of cancer in their children and their
      impact on the maternal role.
AB  - BACKGROUND: Arab culture and Islamic beliefs contribute to values and practices
      regarding cancer. Mothers in Jordanian society are expected to be the primary
      caregivers to children. PURPOSE: The purpose of this study was to explore
      Jordanian mothers' beliefs regarding the causes of cancer in their children and
      their impact on their role as mothers. DESIGN: A descriptive, qualitative design
      was used. Individual interviews were conducted with Jordanian mothers (n = 51) of
      hospitalized children with cancer. RESULTS: Causes of cancer were attributed to
      supernatural explanations and biomedical explanations. The impact of cancer on
      these mothers' lives varied. For some, their child's illness resulted in stronger
      family bonds, whereas for others, the families suffered a state of
      disequilibrium. CONCLUSIONS: Cultural beliefs helped assign meaning to their
      children's illness. The maternal role of Jordanian women was partially fulfilled
      or inadequately performed, which in turn affected the functioning and coping
      abilities of the entire household.

PMID- 23545696
TI  - Measurement equivalence of four psychological questionnaires in native-born
      Germans, Russian-speaking immigrants, and native-born Russians.
AB  - Psychological constructs depend on cultural context. It is therefore important to
      show the equivalence of measurement instruments in cross-cultural research. There
      is evidence that in Russian-speaking immigrants, cultural and language issues are
      important in health care. We examined measurement equivalence of the Patient
      Health Questionnaire-9 (PHQ-9), the Patient Health Questionnaire-15 (PHQ-15), the
      Hamburg Self-Care Questionnaire (HamSCQ), and the questionnaire on communication
      preferences of patients with chronic illness (KOPRA) in native-born Germans,
      Russian-speaking immigrants living in Germany, and native-born Russians living in
      the former Soviet Union (FSU). All four questionnaires fulfilled requirements of
      measurement equivalence in confirmatory factor analyses and analyses of
      differential item functioning. The Russian translations can be used in Russian
      speaking immigrants and native-born Russians. This offers further possibilities
      for cross-cultural research and for an improvement in health care research in
      Russian-speaking immigrants in Germany. The most pronounced differences occurred
      in the KOPRA, which point to differences in German and Russian health care
      systems.

PMID- 23545698
TI  - Through the eyes of the other: using event analysis to build cultural competence.
AB  - Cultural competence requires more than the accumulation of information about
      cultural groups. An awareness of the nurse's own culture, beliefs, and values is
      considered by several transcultural nursing theorists to be essential to the
      development of cultural competence and the provision of quality patient care.
      Using Transformational Learning Theory, this article describes event analysis, an
      active learning tool that uses the nurse's own practice to explore multiple
      perspectives of an experience, with the goal of transforming the nurse's approach
      to diversity from an ethnocentric stance, to one of tolerance and consideration
      for the patient's needs, values, and beliefs with regard to quality of care.
      Furthermore, the application of the event analysis to multiple settings,
      including inpatient, educational, and administrative environments, is discussed.

PMID- 23545697
TI  - Seeking life balance: the perceptions of health of Cambodian women in
      resettlement.
AB  - This grounded theory study in California, United States was an inquiry into the
      perceptions of health of Cambodian women in resettlement. The sequelae of
      significant life trauma on the health of women who escaped political conflict
      have received little attention in the nursing literature. Thirty-nine Cambodian
      women were recruited through a social service organization and verbal referrals.
      Open-ended questions and a conversational approach to dialogue and data gathering
      facilitated the interview process. Women were interviewed at home or the local
      temple. Seeking life balance emerged as the core perspective of this study. The
      relationships between thematic categories of seeking life balance, patterns of
      knowing, and caring for self were salient. Outcomes of these interrelationships
      further moved women's health toward disharmony or harmony. The findings of this
      study are limited by sampling participants in a tightly networked community and
      may serve as a pilot for future research.

PMID- 23545699
TI  - Disregard of patients' preferences is a medical error: comment on "Failure to
      engage hospitalized elderly patients and their families in advance care
      planning".

PMID- 23545700
TI  - Enzyme-based listericidal nanocomposites.
AB  - Cell lytic enzymes represent an alternative to chemical decontamination or use of
      antibiotics to kill pathogenic bacteria, such as listeria. A number of phage cell
      lytic enzymes against listeria have been isolated and possess listericidal
      activity; however, there has been no attempt to incorporate these enzymes onto
      surfaces. We report three facile routes for the surface incorporation of the
      listeria bacteriophage endolysin Ply500: covalent attachment onto FDA approved
      silica nanoparticles (SNPs), incorporation of SNP-Ply500 conjugates into a thin
      poly(hydroxyethyl methacrylate) film; and affinity binding to edible crosslinked
      starch nanoparticles via construction of a maltose binding protein fusion. These
      Ply500 formulations were effective in killing L. innocua (a reduced pathogenic
      surrogate) at challenges up to 10(5) CFU/ml both in non-growth sustaining PBS as
      well as under growth conditions on lettuce. This strategy represents a new route
      toward achieving highly selective and efficient pathogen decontamination and
      prevention in public infrastructure.

PMID- 23545701
TI  - NS-398 enhances the efficacy of bortezomib against RPMI8226 human multiple
      myeloma cells.
AB  - Bortezomib is commonly used in treating multiple myeloma (MM). However, a number
      of patients develop resistance to bortezomib over time. Cox-2 is overexpressed in
      MM cells and contributes to apoptosis resistance and MM development. In the
      present study, RPMI8226 MM cells were treated with the Cox-2 inhibitor NS-398 to
      investigate whether it enhanced the effect of bortezomib on MM. The results
      showed that NS-398 and bortezomib acted synergistically to inhibit growth, arrest
      the cell cycle at the G1 phase and to induce the apoptosis of MM cells. NS-398
      inhibited the NF-kappaB p65 protein levels and the expression of various NF
      kappaB target genes, including cyclin D1, c-Myc, survivin and Bcl-2. In
      conclusion, NS-398 enhanced the efficacy of bortezomib against MM cells in vitro
      and this was associated with the inhibition of NF-kappaB signaling. These
      findings suggest that the combined use of NS-398 and bortezomib may constitute a
      promising novel treatment protocol for MM patients.

PMID- 23545704
TI  - Photovoltaic devices and characterization of a dodecyloxybenzothiadiazole-based
      copolymer.
AB  - A conjugated copolymer based on alternating benzo[1,2-b;3,4-b']dithiophene (BDT)
      donor and dodecyloxy substituted benzo[c][1,2,5]thiadiazole (ABT) acceptor units
      was prepared for application in organic solar cells. A power conversion
      efficiency (PCE) of ~3% with a short-circuit current (Jsc) of 7.63 mA cm(-2), an
      open-circuit voltage (Voc) of 0.71 V and a fill-factor (FF) of 53.74% was
      obtained under the illumination of AM 1.5 solar irradiation (100 mW cm(-2)).
      Photovoltaic devices and their transient properties with a blend of the copolymer
      and the [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) at different ratios
      were studied using transient photovoltage (TPV), transient photocurrent (TPC) and
      atomic force microscopy (AFM) measurements. From the TPV and TPC measurements,
      the charge recombination times (taun) were found to be 21.1 MUs, 12.6 MUs and
      10.5 MUs, and the charge transport times (taud) were 1316 ns, 422 ns and 707 ns
      for the 1 : 0.5, 1 : 1 and 1 : 2 donor/acceptor (D/A) ratios, respectively. The 1
      : 1 D/A ratio showed the shortest charge transport time (taud) and the longest
      charge diffusion length (Ln) according to L(n) [proportionality]
      ?[tau(n)/tau(d)], leading to the highest device performance among the three
      ratios.

PMID- 23545705
TI  - Early postnatal nutrition determines adult physical activity and energy
      expenditure in female mice.
AB  - Decades of research in rodent models has shown that early postnatal overnutrition
      induces excess adiposity and other components of metabolic syndrome that persist
      into adulthood. The specific biologic mechanisms explaining the persistence of
      these effects, however, remain unknown. On postnatal day 1 (P1), mice were
      fostered in control (C) or small litters (SL). SL mice had increased body weight
      and adiposity at weaning (P21), which persisted to adulthood (P180). Detailed
      metabolic studies indicated that female adult SL mice have decreased physical
      activity and energy expenditure but not increased food intake. Genome-scale DNA
      methylation profiling identified extensive changes in hypothalamic DNA
      methylation during the suckling period, suggesting that it is a critical period
      for developmental epigenetics in the mouse hypothalamus. Indeed, SL mice
      exhibited subtle and sex-specific changes in hypothalamic DNA methylation that
      persisted from early life to adulthood, providing a potential mechanistic basis
      for the sustained physiological effects. Expression profiling in adult
      hypothalamus likewise provided evidence of widespread sex-specific alterations in
      gene expression. Together, our data indicate that early postnatal overnutrition
      leads to a reduction in spontaneous physical activity and energy expenditure in
      females and suggest that early postnatal life is a critical period during which
      nutrition can affect hypothalamic developmental epigenetics. 

PMID- 23545706
TI  - PD-1, but not PD-L1, expressed by islet-reactive CD4+ T cells suppresses
      infiltration of the pancreas during type 1 diabetes.
AB  - The inhibitory receptor programmed death-1 (PD-1) constrains type 1 diabetes
      (T1D) in the nonobese diabetic (NOD) mouse. However, how PD-1 influences
      diabetogenic CD4(+) T cells during natural diabetes is not fully understood. To
      address this question, we developed a novel model to investigate antigen-specific
      CD4(+) T cells under physiological conditions in vivo. We transferred a low
      number of naive CD4(+) T cells from the BDC2.5 mouse into prediabetic NOD mice to
      mimic a physiological precursor frequency and allowed the cells to become primed
      by endogenous autoantigen. Transferred BDC2.5 T cells became activated,
      differentiated into T-bet(+) IFN-gamma-producing cells, and infiltrated the
      pancreas. In this model, loss of PD-1, but not programmed death ligand-1 (PD-L1),
      on the antigen-specific CD4(+) T cell resulted in increased cell numbers in the
      spleen, pancreas-draining lymph node, and pancreas. PD-1 deficiency also
      increased expression of the chemokine receptor CXCR3. Lastly, histological data
      showed that a loss of PD-1 caused BDC2.5 cells to penetrate deep into the islet
      core, resulting in conversion from peri-insulitis to destructive insulitis. These
      data support a model by which PD-1 regulates islet-reactive CD4(+) T cells in a
      cell intrinsic manner by suppressing proliferation, inhibiting infiltration of
      the pancreas, and limiting diabetes. 

PMID- 23545707
TI  - Effect of losartan on prevention and progression of early diabetic nephropathy in
      American Indians with type 2 diabetes.
AB  - Angiotensin receptor blockers are renoprotective in hypertensive azotemic
      patients with type 2 diabetes, but their efficacy in early diabetic kidney
      disease is uncertain. We performed a 6-year randomized clinical trial in 169
      American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine
      ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30-299 mg/g; n = 78) at
      baseline. The primary outcome was decline in glomerular filtration rate (GFR) to
      <=60 mL/min or to half the baseline value in subjects who entered with GFR <120
      mL/min. Another outcome was differences in glomerular structure at end of
      treatment. Subjects received 100 mg losartan or placebo daily. GFR was measured
      annually; 111 subjects underwent kidney biopsies. Only nine subjects reached the
      GFR outcome, and the unadjusted hazard ratio (losartan vs. placebo) was 0.50 (95%
      CI, 0.12-1.99). Differences in mesangial fractional volume were not estimated in
      the combined albuminuria groups because of an interaction with treatment
      assignment. In separate analyses, mesangial fractional volume was lower in
      subjects treated with losartan in the microalbuminuria group (18.8 vs. 25.6%; P =
      0.02), but not in the normoalbuminuria group (19.6 vs. 17.8%; P = 0.86).
      Treatment with losartan may preserve some features of kidney structure in
      American Indians with type 2 diabetes and microalbuminuria. 

PMID- 23545708
TI  - Direct effects of exendin-(9,39) and GLP-1-(9,36)amide on insulin action, beta
      cell function, and glucose metabolism in nondiabetic subjects.
AB  - Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at
      its receptor. However, it is unclear if it has direct and unique effects of its
      own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have
      direct effects on hormone secretion and beta-cell function as well as glucose
      metabolism in healthy subjects. Glucose containing [3-(3)H]glucose was infused to
      mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide,
      or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were
      infused in random order on separate days. Integrated glucose concentrations were
      slightly but significantly increased by exendin-(9,39) (365 +/- 43 vs. 383 +/- 35
      vs. 492 +/- 49 vs. 337 +/- 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1
      [9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among
      groups. However, insulin action was lowered by exendin-(9,39) (25 +/- 4 vs. 20 +/
      4 vs. 18 +/- 3 vs. 21 +/- 4 10(-4) dL/kg[min per MUU/mL]; P = 0.02), resulting
      in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 +/- 118
      vs. 816 +/- 83 vs. 725 +/- 127 vs. 955 +/- 166 10(-14) dL/kg/min(2) per pmol/L; P
      = 0.003). Endogenous glucose production and glucose disappearance did not differ
      significantly among groups. We conclude that exendin-(9,39), but not GLP-1
      (9,36)amide, decreases insulin action and DI in healthy humans. 

PMID- 23545709
TI  - Fiber and functional gastrointestinal disorders.
AB  - Despite years of advising patients to alter their dietary and supplementary fiber
      intake, the evidence surrounding the use of fiber for functional bowel disease is
      limited. This paper outlines the organization of fiber types and highlights the
      importance of assessing the fermentation characteristics of each fiber type when
      choosing a suitable strategy for patients. Fiber undergoes partial or total
      fermentation in the distal small bowel and colon leading to the production of
      short-chain fatty acids and gas, thereby affecting gastrointestinal function and
      sensation. When fiber is recommended for functional bowel disease, use of a
      soluble supplement such as ispaghula/psyllium is best supported by the available
      evidence. Even when used judiciously, fiber can exacerbate abdominal distension,
      flatulence, constipation, and diarrhea.

PMID- 23545710
TI  - High economic burden of caring for patients with suspected extraesophageal
      reflux.
AB  - OBJECTIVES: Extraesophageal symptoms are common manifestations of
      gastroesophageal reflux disease (GERD). Lack of a definitive diagnostic or
      treatment standards complicate management, which often leads to multiple
      specialty consultations, procedures, pharmaceuticals and diagnostic tests. The
      aim of this study was to determine the economic burden associated with
      extraesophageal reflux (EER). METHODS: Direct costs of evaluation were estimated
      for patients referred with symptoms attributed to EER between 2007 and 2011.
      Medicare payment for evaluation and management and pharmaceutical prices was used
      to calculate first year and overall costs of evaluating and treating
      extraesophageal symptoms attributed to reflux. RESULTS: Overall, 281 patients
      were studied (cough (50%), hoarseness (23%), globus/post-nasal drainage (15%),
      asthma (9%), and sore throat (3%)). Over a median (interquartile range) of 32 (16
      46) months follow-up, patients had a mean (95% confidence interval) of 10.1 (9.4
      10.9) consultations with specialists and underwent 6.4 (3-9) diagnostic
      procedures. Overall, the mean initial year direct cost was $5,438 per patient
      being evaluated for EER. Medical and non-medical components contributed $5,154
      and $283. Of the overall cost, 52% were attributable to the use of proton pump
      inhibitors. During the initial year, direct costs were 5.6 times higher than
      those reported for typical GERD ($971). A total of 54% of patients reported
      improvement of symptoms. Overall cost per improved patient was $13,700.
      CONCLUSIONS: EER contributes substantially to health-care expenditures. In this
      cohort, the cost for initial year's evaluation and treatment of EER symptoms was
      quintuple that of typical GERD. Prescription costs and, in particular, proton
      pump inhibitors were the single greatest contributor to the cost of EER
      management.

PMID- 23545711
TI  - Biliary self-expandable metal stents do not adversely affect
      pancreaticoduodenectomy.
AB  - OBJECTIVES: Controversy exists regarding whether to place a plastic or a metal
      endobiliary stent in patients with resectable pancreatic cancer who require
      biliary drainage. Although self-expandable metal stents (SEMS) provide better
      drainage compared with plastic stents, concerns remain that SEMS may compromise
      resection and increase postoperative complications. Our objective was to compare
      surgical outcomes of patients undergoing pancreaticoduodenectomy (PD) with SEMS
      in place vs. plastic endoscopic stents (PES) and no stents (NS). METHODS: We
      performed a retrospective analysis from a prospective database of all patients
      undergoing either attempted or successful PD with SEMS, PES, or NS in place at
      the time of operation. Patients were compared with regard to perioperative
      complications, margin status, and the rate of intraoperative determination of
      unresectability. RESULTS: A total of 593 patients underwent attempted PD. Of
      these, 84 patients were locally unresectable intraoperatively and 509 underwent
      successful PD, of which 71 had SEMS, 149 had PES, and 289 had NS. Among patients
      who had a preoperative stent, SEMS did not increase overall or serious
      postoperative complications, 30-day mortality, length of stay, biliary
      anastomotic leak, or positive margin, but was associated with more wound
      infections and longer operative times. In those with adenocarcinoma,
      intraoperative determination of local unresectability was similar in the SEMS
      group compared with other groups, with 16 (19.3%) in SEMS compared with 29
      (17.7%) in PES (P=0.862), and 31 (17.5%) in NS (P=0.732). CONCLUSIONS: Placement
      of SEMS is not contraindicated in patients with resectable pancreatic cancer who
      require preoperative biliary drainage.

PMID- 23545712
TI  - The role of food in the functional gastrointestinal disorders: introduction to a
      manuscript series.
AB  - Functional gastrointestinal disorders (FGIDs) are characterized by the presence
      of chronic or recurrent symptoms that are felt to originate from the
      gastrointestinal (GI) tract, which cannot be attributed to an identifiable
      structural or biochemical cause. Food is associated with symptom onset or
      exacerbation in a significant proportion of FGID patients. Despite this, the role
      of food in the pathogenesis of the FGIDs has remained poorly understood. For this
      reason, diet has largely played an adjunctive rather than a primary role in the
      management of FGID patients. In recent years, there has been a rapid expansion in
      our understanding of the role of food in GI function and sensation and how food
      relates to GI symptoms in FGID patients. In a series of evidence-based
      manuscripts produced by the Rome Foundation Working Group on the role of food in
      FGIDs, comprehensive reviews of the physiological changes associated with
      nutrient intake, and the respective roles of carbohydrates, fiber, protein, and
      fats are provided. The series concludes with a manuscript that provides guidance
      on proper clinical trial design when considering the role of food in FGIDs.

PMID- 23545713
TI  - Relationship of non-alcoholic fatty liver disease with cholecystectomy in the US
      population.
AB  - OBJECTIVES: Other than weight-related conditions, risk factors for non-alcoholic
      fatty liver disease (NAFLD) are not well defined. We investigated the association
      of gallstones and cholecystectomy with NAFLD in a large, national, population
      based study. METHODS: Among adult participants in the third US National Health
      and Nutrition Examination Survey, 1988-1994, ultrasonography for gallstone
      disease was performed, and videotapes were subsequently evaluated for NAFLD. Odds
      ratios (ORs) for the association of gallstone disease with NAFLD were calculated
      using logistic regression analysis to adjust for common associated factors.
      RESULTS: Among 12,232 participants without viral hepatitis or significant alcohol
      intake, the prevalence of gallstones was 7.4%, cholecystectomy 5.6%, and NAFLD
      20.0%. Participants with cholecystectomy had higher age-sex-adjusted prevalence
      of NAFLD (48.4%) than those with gallstones (34.4%) or without gallstone disease
      (17.9%) (P<0.01 for all comparisons). Controlling for numerous factors associated
      with both NAFLD and gallstone disease, multivariate-adjusted analysis confirmed
      the association of NAFLD with cholecystectomy (OR=2.4; 95% confidence interval
      (CI): 1.8-3.3), but not with gallstones (OR=1.1; 95% CI: 0.84-1.4). CONCLUSIONS:
      The association of NAFLD with cholecystectomy, but not with gallstones, indicates
      that cholecystectomy may itself be a risk factor for NAFLD.

PMID- 23545715
TI  - The association of serum lipids with colorectal adenomas.
AB  - OBJECTIVES: There is suggestive but sparse evidence that dyslipidemia is
      associated with colorectal neoplasms. We investigated the association of serum
      lipid and apolipoprotein concentrations with the prevalence of colorectal
      adenomas. METHODS: Cross-sectional study of 19,281 consecutive participants aged
      40-79 years undergoing screening colonoscopy at the Center for Health Promotion
      of the Samsung Medical Center in Korea from January 2006 to June 2009. RESULTS:
      We identified 5,958 participants with colorectal adenomas (30.9%), including
      5,504 (28.5%) with non-advanced adenomas and 454 (2.4%) with advanced adenomas.
      The adjusted relative prevalence ratios (aRPRs) comparing the fourth with the
      first quartiles of serum triglycerides were 1.35 (95% confidence interval (CI)
      1.20-1.52; P trend<0.001) for non-advanced adenomas and 1.45 (95% CI 1.02-2.06; P
      trend=0.005) for advanced adenomas. Higher levels of high-density lipoprotein
      (HDL) cholesterol and apolipoprotein A-1 (ApoA-1) were significantly associated
      with 12% (Q4 vs. Q1 aRPR 1.12; 95% CI 1.00-1.26; P trend=0.049) and 17% (Q4 vs.
      Q1 aRPR 1.17; 95% CI 1.04-1.31; P trend=0.004) higher prevalence of non-advanced
      adenoma. There was also a non-significant association between higher levels of
      low-density lipoprotein (LDL) cholesterol (Q4 vs. Q1 aRPR 1.22; 95% CI 0.91-1.66;
      P trend= 0.12) and apolipoprotein B (ApoB) (Q4 vs. Q1 aRPR 1.32; 95% CI 0.94
      1.83; P trend=0.07) with higher prevalence of advanced adenoma. There was no
      association between total cholesterol levels with colorectal adenoma.
      CONCLUSIONS: In this large cross-sectional study, higher levels of serum
      triglycerides were significantly associated with an increasing prevalence of both
      non-advanced and advanced colorectal adenomas, while higher levels of ApoA-1 and
      HDL cholesterol were significantly associated with an increasing prevalence of
      non-advanced adenomas.

PMID- 23545714
TI  - The Western dietary pattern is prospectively associated with nonalcoholic fatty
      liver disease in adolescence.
AB  - OBJECTIVES: Poor dietary habits have been implicated in the development of
      nonalcoholic fatty liver disease (NAFLD); however, little is known about the role
      of specific dietary patterns in the development of NAFLD. We examined prospective
      associations between dietary patterns and NAFLD in a population-based cohort of
      adolescents. METHODS: Participants in the Western Australian Pregnancy Cohort
      (Raine) Study completed a food frequency questionnaire at 14 years and had liver
      ultrasound at 17 years (n=995). Healthy and Western dietary patterns were
      identified using factor analysis and all participants received a z-score for
      these patterns. Prospective associations between the dietary pattern scores and
      risk of NAFLD were analyzed using multiple logistic regression. RESULTS: NAFLD
      was present in 15.2% of adolescents. A higher Western dietary pattern score at 14
      years was associated with a greater risk of NAFLD at 17 years (odds ratio (OR)
      1.59; 95% confidence interval (CI) 1.17-2.14; P<0.005), although these
      associations were no longer significant after adjusting for body mass index at 14
      years. However, a healthy dietary pattern at 14 years appeared protective against
      NAFLD at 17 years in centrally obese adolescents (OR 0.63; 95% CI 0.41-0.96;
      P=0.033), whereas a Western dietary pattern was associated with an increased risk
      of NAFLD. CONCLUSIONS: A Western dietary pattern at 14 years in a general
      population sample was associated with an increased risk of NAFLD at 17 years,
      particularly in obese adolescents. In centrally obese adolescents with NAFLD, a
      healthy dietary pattern may be protective, whereas a Western dietary pattern may
      increase the risk.

PMID- 23545716
TI  - Suicide within two weeks of discharge from psychiatric inpatient care: a case
      control study.
AB  - OBJECTIVE: Suicide risk after discharge from psychiatric inpatient care is high,
      particularly in the first few weeks. The aim of the study was to identify risk
      factors and protective factors (that is, factors associated with a reduced risk
      of suicide), including variation in health care received, for suicide among
      patients in the two-week postdischarge period. METHODS: This was a national
      population-based retrospective case-control study of 100 psychiatric patients in
      England (2004-2006), age 18-65, who died by suicide within two weeks of hospital
      discharge. These patients were matched on discharge date with 100 living control
      group patients. RESULTS: Fifty-five percent of suicides occurred within a week of
      discharge, 49% of whom died before their first follow-up appointment. Conditional
      logistic regression analyses indicated that recent adverse life events and a
      short (less than one week) final admission were independently associated with
      postdischarge suicide, as were older age and comorbid psychiatric disorders.
      Receiving enhanced aftercare (under the Care Programme Approach) was protective
      of suicide. CONCLUSIONS: Discharged patients viewed as being at high risk of
      suicide require immediate community follow-up. Mental health services should be
      mindful of discharging patients after a short admission. The potential role of
      detrimental life experiences indicates that mental health clinicians need to be
      aware of the circumstances into which patients are being discharged. Use of
      enhanced levels of care, such as that offered by the Care Programme Approach, may
      play a strong role in preventing suicide within two weeks of discharge.

PMID- 23545718
TI  - Cytohesin-2 as a novel prognostic marker for hepatocellular carcinoma.
AB  - Cytohesin-2 is overexpressed in human lung cancer and it activates cytoplasmic
      ErbB receptors. Inhibition of cytohesin-2 by SecinH3 reduces growth of EGFR
      dependent lung cancer xenografts and improves the treatment of primarily EGFR-TKI
      resistant lung cancers. Cytohesin-2 promotes HepG2 proliferation through the IGF
      pathway, and VEGF-dependent initiation of angiogenesis by regulation of VEGFR-2
      internalization in endothelial cells, vessel permeability and ultimately
      endothelial proliferation. The purpose of this study was to evaluate the effects
      of cytohesin-2 in hepatocellular carcinoma (HCC). In the current study, we
      collected 40 HCC tissues and detected cytohesin-2 mRNA expression in the 40 HCC
      tissues by using quantitative real-time polymerase chain reaction (qRT-PCR), as
      well as its protein expression by using immunohistochemistry and western blot
      analysis. We found that cytohesin-2 was more highly expressed in HCC compared to
      adjacent non-tumorous liver tissues, and cytohesin-2 expression was significantly
      increased in specimens with high alpha-fetoprotein and vascular invasion. Both
      univariate and multivariate analyses indicated that there is an association
      between cytohesin-2 expression and overall survival (OS) and disease-free
      survival (DFS). Moreover, stratified analysis showed that patients in tumor-node
      metastasis (TNM) stage I with higher cytohesin-2 levels had shorter OS and DFS
      than those with lower cytohesin-2 levels. In conclusion, cytohesin-2 may identify
      low-and high-risk individuals with HCC and may be a valuable indicator for
      stratifying prognosis of TNM stage I patients. Cytohesin-2 may serve as a novel
      prognostic biomarker for HCC.

PMID- 23545719
TI  - Expression and localisation of osteopontin and prominin-1 (CD133) in patients
      with endometriosis.
AB  - In this study, we investigated the expression and localisation of the proteins,
      osteopontin (OPN) and prominin-1 (CD133), as well as the plasma OPN levels in the
      endometrium of patients with endometriosis. Samples of ectopic endometriotic
      lesions and normal endometrium were obtained from 31 women with endometriosis and
      28 healthy control subjects. The mRNA and protein expression of OPN and CD133 was
      analysed by real-time RT-PCR and immunohistochemistry. The plasma levels of OPN
      were determined by ELISA. Our results revealed that OPN mRNA and protein
      expression, as well as its release in the blood, was significantly increased in
      the endometriotic lesions in comparison to normal tissue. Although the presence
      of CD133+ cells was detected in the normal endometrium, as well as in the
      endometriosis specimens, a significant quantitative variation of this protein was
      not demonstrated in the patients with endometriosis. In conclusion, our data
      indicate that OPN is involved in the development of endometriosis by enhancing
      the invasiveness, proliferation and survival of endometrial cells in ectopic
      lesions. CD133 cannot be used as a disease marker for endometriosis, although an
      involvement of this protein in the pathogenesis of endometriosis cannot be
      excluded.

PMID- 23545720
TI  - "If it isn't ultimately aimed at policy, it's not worth doing": interview of
      George W. Comstock by Alfredo Morabia.
AB  - George W. Comstock (1915-2007), MD, MPH, DrPH, was lecturer and then professor of
      epidemiology at the Johns Hopkins University School of Hygiene and Public Health
      from 1956 to 2007 and served as editor-in-chief of the American Journal of
      Epidemiology from 1979 to 1988. This interview of George W. Comstock took place
      in Hagerstown, Maryland, in the spring of 1990. The selection of questions and
      answers published here represent approximately 10% of the whole interview, which
      had been reviewed and hand-corrected by Dr. Comstock. He first describes how
      epidemiology was taught at Hopkins in the 1950s and 1960s. He then distinguishes
      "epidemiology per se" from a "practical epidemiology" that works closely with
      local health departments, and he finally expresses his wish that in the future,
      epidemiology would become more widely involved in policy and accepted by policy
      makers.

PMID- 23545721
TI  - The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced
      cardiotoxicity.
AB  - Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18 %
      patients. The metabolic profile of MTX was assessed after incubation of 100 MUM
      MTX with hepatic S9 fraction isolated from rats. The presence of MTX and its
      metabolites was also assessed in vivo through the analysis of liver and heart
      extracts of MTX-treated rats. The cytotoxic effects of MTX and MTX metabolites
      were evaluated in the H9c2 cells after 24-h incubation with MTX alone and MTX +
      metabolites. The influence of CYP450- and CYP2E1-mediated metabolism for the
      cytotoxicity of MTX was assessed after 96-h incubation with MTX (100 nM and 1
      MUM) in the presence/absence of CYP450 or CYP2E1 inhibitors. After 4-h incubation
      in supplemented S9 fraction, the MTX content was 35 % lower and 5 metabolites
      were identified: an acetoxy ester derivative (never described before), two
      glutathione conjugates, a monocarboxylic acid derivative, and the
      naphtoquinoxaline, the later commonly related to MTX pharmacological effects. The
      presence of MTX and naphtoquinoxaline metabolite was evidenced in vivo in liver
      and heart of MTX-treated rats. The cytotoxicity caused by MTX + metabolites was
      higher than that observed in the H9c2 cells incubated with non-metabolized MTX
      group. The co-incubation of MTX with CYP450 and CYP2E1 inhibitors partially
      prevented the cytotoxicity observed in the MTX groups incubated with H9c2 cells,
      highlighting that the metabolism of MTX is relevant for its undesirable effects.
      The naphtoquinoxaline metabolite is described in heart and liver in vivo,
      highlighting that this metabolite accumulates in these tissues. It was
      demonstrated that MTX P450-mediated metabolism contributed to MTX toxicity.

PMID- 23545723
TI  - Displaced clavicle fractures in adolescents: facts, controversies, and current
      trends.

PMID- 23545724
TI  - Thank you, Adria.

PMID- 23545725
TI  - Update on surgery of the hand.

PMID- 23545726
TI  - Meniscal repair.
AB  - Historically, treatment of meniscus tears consisted of complete meniscectomy.
      Over the past few decades, however, the long-term morbidities of meniscal
      removal, namely the early development of knee osteoarthritis, have become
      apparent. Thus, management of meniscal tears has trended toward meniscal
      preservation. Recent technological advances have made repairs of the meniscus
      easier and stronger. In addition, adjunctive therapies used to enhance the
      healing process have advanced greatly in the past few years. Today, with
      increased understanding of the impact of meniscal loss and the principles of
      meniscal repair and healing, meniscal preservation is viewed as an increasingly
      realistic and important goal in the management of meniscus tears.

PMID- 23545727
TI  - Snapping scapula syndrome: diagnosis and management.
AB  - Scapulothoracic bursitis and snapping scapula syndrome are rare diagnoses that
      contribute to considerable morbidity in some patients. These conditions represent
      a spectrum of disorders characterized by pain with or without mechanical
      crepitus. They are commonly identified in young, active patients who perform
      repetitive overhead activities. Causes include anatomic scapular or thoracic
      variations, muscle abnormalities, and bony or soft-tissue masses. Three
      dimensional CT and MRI aid in detecting these abnormalities. Nonsurgical therapy
      is the initial treatment of choice but is less successful than surgical
      management in patients with anatomic abnormalities. In many cases, scapular
      stabilization, postural exercises, or injections eliminate symptoms. When
      nonsurgical treatment fails, open and endoscopic techniques have been used with
      satisfactory results. Familiarity with the neuroanatomic structures surrounding
      the scapula is critical to avoid iatrogenic complications. Although reported
      outcomes of both open and endoscopic scapulothoracic decompression are
      encouraging, satisfactory outcomes have not been universally achieved.

PMID- 23545728
TI  - Chondroblastoma and chondromyxoid fibroma.
AB  - Chondroblastoma and chondromyxoid fibroma are benign but locally aggressive bone
      tumors. Chondroblastoma, a destructive lesion with a thin radiodense border, is
      usually seen in the epiphysis of long bones. Chondromyxoid fibroma presents as a
      bigger, lucent, loculated lesion with a sharp sclerotic margin in the metaphysis
      of long bones. Although uncommon, these tumors can be challenging to manage. They
      share similarities in pathology that could be related to their histogenic
      similarity. Very rarely, chondroblastoma may lead to lung metastases; however,
      the mechanism is not well understood.

PMID- 23545729
TI  - Pediatric physeal ankle fracture.
AB  - Ankle fracture is the second most common fracture type in children, and physeal
      injury is a particular concern. Growing children have open physes that are
      relatively weak compared with surrounding bone and ligaments, and traumatic
      injuries can cause physeal damage and fracture. Tenderness to palpation over the
      physis can aid in the clinical diagnosis of ankle fracture. Swelling, bruising,
      and deformity may be identified, as well. Plain radiographs are excellent for
      initial evaluation, but CT may be required to determine displacement and to aid
      in surgical planning, particularly in the setting of intra-articular fractures.
      The Salter-Harris classification is the most widely used system to determine
      appropriate management and assess long-term prognosis. Complications of physeal
      injury include shortening and/or angular deformity. Tillaux and triplane
      fractures occur in the 18-month transitional period preceding physeal closure,
      which typically occurs at age 14 years in girls and age 16 years in boys.
      Management is determined by the amount of growth remaining, with the intent of
      maintaining optimum function while limiting the risk of physeal damage and joint
      incongruity.

PMID- 23545730
TI  - Understanding systematic reviews and meta-analyses in orthopaedics.
AB  - The systematic literature review is a powerful tool for summarizing and
      evaluating current knowledge related to a specific research question. Systematic
      reviews have many advantages over traditional narrative reviews. A meta-analysis
      of data from a systematic review can provide a better estimate of a treatment
      effect than can individual studies. To ensure quality conclusions, rigorous
      methods must be applied to systematic reviews, such as formulation of a specific
      research question, systematic literature search, selection and assessment of
      included studies, data extraction, quality assessment of included studies, meta
      analysis and presentation of results, and formation of conclusions. Threats to
      the internal validity and generalizability of the conclusions of systematic
      reviews include lack of clarity or appropriateness of the research question, poor
      quality of the included studies, heterogeneity of results between studies,
      inappropriate conclusions, and inappropriate application in clinical practice.

PMID- 23545731
TI  - Annexins: novel therapeutic targets for the treatment of osteoarthritis?

PMID- 23545732
TI  - Synovial stem cells in musculoskeletal regeneration.

PMID- 23545733
TI  - Bone: maternal vitamin D status--not the key to offspring bone health?

PMID- 23545736
TI  - [Excitation-Contraction coupling and intracellular calcium cycling in failing
      hearts].
AB  - Alterations in Excitation-Contraction coupling have recently been shown to play a
      crucial role in the pathogenesis of heart failure (HF). In failing hearts,
      abnormalities of neurohormonal mechanisms, which were included chronic activation
      of the sympathetic nervous system or of the renin-angiotensin system result in
      structural and functional changes in the calcium (Ca(2 +) ) regulatory proteins.
      These changes include the decreased sarcoplasmic reticulum (SR) load, which could
      be caused by reduced SR Ca(2 +) -ATPase (SERCA2A) function and increased SR Ca(2
      +) leak via cardiac ryanodine receptor (RyR2) , a functional defect in L-type
      Ca(2 +) channel and activation of the reversal mode of Na (+) /Ca(2 +) exchanger.
      The abnormal regulation of intracellular Ca(2 +) affects troponin C binding and
      actin-myosin cross bridging and modulates post signaling pathway, which in turn
      contributes to the contractile dysfunction of hearts and hence to the progression
      of HF. Moreover, diastolic Ca(2 +) leak may develop delayed after depolarization
      and triggered activity as a substrate for lethal arrhythmia and sudden cardiac
      death. In this review, we focus on the underlying mechanism of defective Ca(2 +)
      regulation in HF and on the possibility of proceeding to clinical application as
      a new treatment for HF by targeting Ca(2 +) regulatory proteins.

PMID- 23545737
TI  - [The role of angiogenetic factors in the pathogenesis and the progression of
      cardiac valve disease].
AB  - Recently, the aging of population and the changing dietary habit to western-style
      have led to increase in atherosclerotic diseases, such as myocardial infarction
      and cerebral infarction, in our country. Aortic valve diseases, whose mechanism
      is similar to atherosclerosis, are also increasing. The medication proved to be
      effective does not exist, and surgical management is major in treatment of these
      diseases. Although development of safer medication is expected, little is known
      about their molecular mechanism of the pathogenesis and the progression. The
      balance of angiogenetic and angioinhibitory factors is important for normal
      developing and homeostasis in many organs. The tissue of cardiac valves is mostly
      avascular like cartilages and tendons, although the heart is the organ having
      abundance of vessels. We focused on angiogenetitic and angioinhibitory factors
      expressing in the cartilages and tendons, and found Chondromodulin- I,
      Tenomodulin and Periostin have crucial roles in degeneration of the cardiac valve
      by controlling angiogenesis and production of Matrix metalloproteinase protein
      (MMP) . Now, we review the mechanism of cardiac valve disease focusing on the
      role of angiogenetic factors.

PMID- 23545735
TI  - Biologic agents in osteoarthritis: hopes and disappointments.
AB  - New treatment options are needed for osteoarthritis (OA) to slow down the
      structural progression of the disease; current therapies mostly target pain and
      function with minimal effectiveness. OA results from an imbalance between
      catabolic and anabolic factors, and biologic agents either target specific
      catabolic proinflammatory mediators, such as cytokines, nitric oxide synthesis,
      or affect anabolism more generally. Biologic agents have dramatic effects in
      other rheumatic inflammatory diseases such as rheumatoid arthritis; they were
      hoped to have similar effects in the treatment of OA. In this Review, we will
      discuss the three main types of cytokine blockers used in knee and hand OA, which
      target beta-nerve growth factor (beta-NGF), IL-1beta or TNF. We will also discuss
      inhibitors of nitrogen oxide production and the use of growth factors to treat
      OA. Among the targeted agents, anti-beta-NGF therapy has shown promising results,
      although cases of rapid destructive arthropathy caution against its widespread
      use. The future of therapies targeting cytokines, nitrogen oxide synthesis and
      growth factors in OA is questionable, as results from clinical trials have been
      repeatedly negative. Strategies in OA therapy need to be reconsidered. New
      molecules emerging from preclinical data should focus on treating the early phase
      of the disease where damage may be reversible, and treatment should be modified
      to fit each patient. 

PMID- 23545734
TI  - The phenotypic and genetic signatures of common musculoskeletal pain conditions.
AB  - Musculoskeletal pain conditions, such as fibromyalgia and low back pain, tend to
      coexist in affected individuals and are characterized by a report of pain greater
      than expected based on the results of a standard physical evaluation. The
      pathophysiology of these conditions is largely unknown, we lack biological
      markers for accurate diagnosis, and conventional therapeutics have limited
      effectiveness. Growing evidence suggests that chronic pain conditions are
      associated with both physical and psychological triggers, which initiate pain
      amplification and psychological distress; thus, susceptibility is dictated by
      complex interactions between genetic and environmental factors. Herein, we review
      phenotypic and genetic markers of common musculoskeletal pain conditions,
      selected based on their association with musculoskeletal pain in previous
      research. The phenotypic markers of greatest interest include measures of pain
      amplification and 'psychological' measures (such as emotional distress, somatic
      awareness, psychosocial stress and catastrophizing). Genetic polymorphisms
      reproducibly linked with musculoskeletal pain are found in genes contributing to
      serotonergic and adrenergic pathways. Elucidation of the biological mechanisms by
      which these markers contribute to the perception of pain in these patients will
      enable the development of novel effective drugs and methodologies that permit
      better diagnoses and approaches to personalized medicine.

PMID- 23545738
TI  - [Role of calcium and phosphate in atherosclerosis and vascular calcification].
AB  - Serum calcium and phosphate levels are tightly regulated by parathyroid hormone
      and vitamin D. Dysregulation of this homeostasis in patients with chronic kidney
      disease (CKD) contributes to the development of secondary hyperparathyroidism,
      which in turn induces cardiovascular disease as well as the further deterioration
      of the kidney function and bone abnormality, and eventually increases mortality
      and morbidity. Evidence for the relationship between circulating fibroblast
      growth factor 23 (FGF23) levels and the incidence of cardiovascular mortality has
      been accumulated. With the discovery of FGF23/klotho axis, we gained the
      understanding of adaptation and maladaptation of the phosphate handling in CKD
      patients. The research for the direct or indirect sequelae of increased serum
      FGF23 concentrations should be warranted.

PMID- 23545739
TI  - [Hypertension and osteoporosis].
AB  - The number of patients with high blood pressure and osteoporosis are increased
      year by year in our society. In hypertension patients, excess urinary calcium
      secretion induces secondary parathyroidism to increase serum calcium level by
      calcium release from bone, which may accelerate osteoporosis. In this aspect,
      there are several reports that anti-hypertensive drugs, especially thiazides,
      increase bone mineral density and decrease the incidence of bone fracture. In
      addition, we demonstrated that renin-angiotensin system can be involved in the
      process of osteoporosis. Angiotensin II significantly induced the expression of
      RANKL (receptor activator of NF-kappaB ligand) in osteoblasts, leading to the
      activation of osteoclasts, while these effects were completely blocked by an Ang
      II type 1 receptor blockade. Recently, it has been reported that angiotensin
      receptor blockade clinically decreased the incidence of bone fracture. Renin
      angiotensin system might be common molecule to regulate both hypertension and
      osteoporosis.

PMID- 23545740
TI  - [Calcium dependent signaling in cardiac hypertrophy and cell death].
AB  - Ca(2 +) plays a pivotal role in excitation-contraction coupling as well as
      activation of Ca(2 +) -dependent signaling pathways in the myocardium. The two
      main established Ca(2 +) -dependent pathways during cardiomyocyte hypertrophy are
      the Ca(2 +) /calmodulin-calcineurin-NFAT and the Ca(2 +) /calmodulin dependent
      kinases II -HDAC-MEF2. Both pathways are involved in the transcriptional control
      of many hypertrophic genes. Recently, cyclophilin D, an immunophilin located on
      mitochondrial inner membrane, has been highlighted as a regulator of calcium
      mediated mitochondrial permeability transition in necrotic cardiac cell death.

PMID- 23545741
TI  - [The physiological and pathological function of Ca(2 +) -dependent cysteine
      protease (Calpain) ].
AB  - Calpains are Ca(2 +) -dependent cysteine proteases. Fifteen gene products of
      calpains are expressed in mammals. Among them, Calpain 1 and Calpain 2 are
      ubiquitously expressed and have been investigated extensively. Under the
      physiological conditions, calpain activity is strictly regulated by endogenous
      inhibitory protein, Calpastatin. Calpains are activated in the various
      cardiovascular diseases and implicated in their pathogenesis by degrading
      numerous target proteins. Here we briefly summarize the physiological and
      pathological role of calpains in the cardiovascular diseases.

PMID- 23545742
TI  - [Spatiotemporal regulation of Ca(2 +) dynamics in live cells revealed by Ca(2 +)
      imaging].
AB  - Advance in the live imaging technology revealed that cells display a variety of
      Ca(2 +) dynamics, such as the wave, oscillation, blip, puff and spark.
      Accumulating evidences suggest that not only Ca(2 +) itself, but its spatio
      temporal dynamics are the important information carrier in the physiological
      responses. Here, we will introduce the pattern of Ca(2 +) dynamics along with the
      latest version of high-performance Ca(2 +) probes.

PMID- 23545743
TI  - [Modification of sarco-endoplasmic reticulum Ca(2 +) -ATPase in the failing
      cardiomyocyte].
AB  - The amplitude and velocity of intracellular Ca(2 +) cycling determines
      contractility in normal and failing hearts. Cardiac sarcoplasmic reticulum (SR)
      is a specialized membranous organelle which determines the property of such
      intracellular calcium transport in cardiomyocytes. In the SR membrane, sarco
      endoplasmic reticulum ATPase (SERCA2a) sequestrates Ca(2 +) from the cytosol to
      the SR, thereby regulating cardiac diastolic performance. In the failing hearts,
      depressed SERCA2a function has been shown to be associated with impaired
      contractility and aberrant increase in cytosolic Ca(2 +) concentration.
      Therefore, molecular targeting of SERCA2a complexes becomes an emerging
      therapeutic target. In this review, mechanisms modifying SERCA2a function and
      associated topics is reviewed.

PMID- 23545744
TI  - [TRIC channel and hypertension].
AB  - TRIC channel subtypes form bullet-shaped homo-trimeric assemblies and behave as K
      (+) channels in intracellular membrane systems. The pathophysiological defects
      observed in knockout mice suggest that TRIC channels mediate counter-K (+)
      movements to facilitate Ca(2 +) release from intracellular stores in various cell
      types. In vascular smooth muscle cells (VSMCs) , Ca(2 +) release mediated by
      ryanodine receptors (RyRs) generates local Ca(2 +) sparks, which activate cell
      surface Ca(2 +) -dependent K (+) channels and induce hyperpolarization. Tric-a
      knockout mice develop hypertension due to elevated resting tonus in the mutant
      VSMCs. In Tric-a-knockout VSMCs, RyR-mediated Ca(2 +) sparks are compromised and
      the hyperpolarization signaling is thus impaired. Under such depolarized
      conditions, voltage-dependent L-type Ca(2 +) channels are hyper-activated to
      enhance resting tonus in Tric-a-knockout VSMCs. Therefore, the expression level
      of TRIC-A channels in VSMCs seems to set resting blood pressure at whole animal
      level. Moreover, our association study identified several single nucleotide
      polymorphisms (SNPs) around the TRIC-A gene that increase a hypertension risk and
      restrict the efficiency of antihypertensive drugs. The observations suggest that
      the TRIC-A SNPs can provide biomarkers for the diagnosis and personalized medical
      treatment of essential hypertension.

PMID- 23545745
TI  - [Molecular pathogenesis of primary cardiomyopathy and calcium sensitivity].
AB  - Idiopathic cardiomyopathy (ICM) is defined as the cardiac disease caused by
      functional abnormality of cardiomyocytes, which can be classified into several
      clinical phenotypes such as hypertrophic cardiomyopathy (HCM) and dilated
      cardiomyopathy (DCM) . Familial occurrence is well recognized for ICM, and
      genetic analyses have revealed that mutations in genes for components of
      contractile elements, Z-disc, I band elements, sarcolemma, sarcoplasmic reticulum
      and nuclear membrane cause ICM. Functional abnormality caused by the mutations
      can be categorized into several groups including abnormal calcium sensitivity in
      contraction, abnormal stretch response, and abnormal response to metabolic
      stress.

PMID- 23545746
TI  - [Function and role of transient receptor potential channels].
AB  - Transient receptor potential (TRP) proteins are components of Ca(2 +) -permeable
      non-selective cation channels activated by physical and chemical stimulus except
      for membrane depolarization. The pathophysiological role of TRP channels is
      documented in heart failure. Especially, canonical TRP subfamily C (TRPC)
      channels activated by neurohumoral factors have been implicated in the structural
      remodeling of the heart. TRPC proteins act not only as components of receptor
      activated cation channels, but also as protein scaffold to form protein complex
      with intracellular signaling proteins, leading to amplification of receptor
      signaling. Recently, selective inhibitors of TRPC channels have been continuously
      identified, anticipating the possibility of drug discovery targeting TRPC
      channels for the treatment of heart failure.

PMID- 23545747
TI  - [Pleiotropic effects of new generation calcium channel blockers on cardiovascular
      protections].
AB  - Calcium channel blockers (CCBs) are widely used to treat hypertension and
      generally act on L-type calcium channels. Recent studies have reported that some
      CCBs can also block channels belonging to other subtypes, such as N-type and T
      type channels. N-type calcium channels are present at sympathetic nerve
      terminals. T-type calcium channels are identified as an important molecular
      target in various organs such as the cardiac sinus node and the afferent and
      efferent arterioles. Blockade of N-type or T-type calcium channels resulted in
      reduction of glomerular capillary pressure, a stabilization of renin-angiotensin
      aldosterone system and sympathetic nervous system. Therefore, the blockade of non
      L-type calcium channels has unique pharmacological features of renoprotective,
      vascular endothelial protective, and cardioprotective effects. These new
      generation CCBs have special therapeutic qualities beyond their primary blood
      pressure lowering effects through the blocking of L-type calcium channels. The
      strategy for hypertension treatment with CCBs has entered a new era. We review
      the pleiotropic effects of CCBs on cardiovascular protections.

PMID- 23545748
TI  - [Clinical significance of calcium sensitizer].
AB  - Oral inotropes did not always improve mortality of the patients with heart
      failure partly because of possible direct toxic effects of these agents on
      myocytes, exacerbating arrhythmias, enhancing neurohormonal activity. Ca(2 +)
      sensitizers such as pimobendan and levosimendan was expected to improve even
      mortality of the patients with heart failure through increasing cardiac
      contractility without a rise in intracellular calcium. However, the trials using
      these agents disappoint our expectations. We need the development of the agents
      which has more specific effect of Ca(2 +) sensitizing and the selection of the
      patients who will receive the benefits of Ca(2 +) sensitizers.

PMID- 23545749
TI  - [Associations between calcium intake and risk of cardiovascular disease].
AB  - We reviewed epidemiologic evidence regarding the associations between dietary or
      supplementary calcium intake and risk of cardiovascular disease. Dietary calcium
      intake, especially from milk and dairy foods, was inversely associated with risk
      of stroke among Asians and American women, but not among American men and
      Europeans. Supplementary calcium intake was not associated with risk of stroke.
      As for coronary heart disease, dietary calcium intake was not associated with the
      risk in most of the previous studies. Supplementary calcium intake was positively
      associated with risk of coronary heart disease. In conclusion, dietary calcium
      intake may be beneficial for the prevention of stroke in Japanese whose average
      intake of calcium is low.

PMID- 23545750
TI  - Prenatal human skin expresses the antimicrobial peptide RNase 7.
AB  - Antimicrobial peptides and proteins (AMPs) play important roles in skin immune
      defense due to their capacity to inhibit growth of microbes. During intrauterine
      life, the skin immune system has to acquire the prerequisites to protect the
      newborn from infection in the hostile environment after birth, which includes the
      production of skin AMPs. The aim of this study was to analyze the expression of
      RNase 7, HBD-2/3 and psoriasin during human skin development, thus, providing a
      deeper insight about the maturity of a fundamental component of the innate immune
      system. We found low RNase 7 expression levels in the periderm but no expression
      of HBD-2/3 and psoriasin in first trimester human skin using
      immunohistochemistry. At the end of the second trimester, RNase 7 is expressed
      weakly in all epidermal layers with a marked signal in the stratum corneum. HBD-3
      and psoriasin are focally expressed while HBD-2 is not detectable. Analysis of
      supernatants from cultured prenatal skin cells showed that in contrast to adult
      control, RNase 7 and psoriasin are not found in prenatal skin, suggesting that
      AMPs are detectable but are not secreted. This study shows the differential
      expression of AMPs in developing, non-perturbed human prenatal skin. It is
      conceivable that the combined expression of RNase 7, HBD-3 and psoriasin in fetal
      skin constitutes a developmental program to exert a broad spectrum of
      antimicrobial activity to maintain sterility in the amniotic cavity. 

PMID- 23545751
TI  - Calponin 3 regulates stress fiber formation in dermal fibroblasts during wound
      healing.
AB  - Skin wound healing is an intricate process involving various cell types and
      molecules. In granulation tissue, fibroblasts proliferate and differentiate into
      myofibroblasts and generate mechanical tension for wound closure and contraction.
      Actin stress fibers formed in these cells, especially those containing alpha
      smooth muscle actin (alpha-SMA), are the central machinery for contractile force
      generation. In the present study, calponin 3 (CNN3), which has a phosphorylation
      dependent actin-binding property, was identified in the molecular mechanism
      underlying stress fiber formation. CNN3 was expressed by
      fibroblasts/myofibroblasts in the proliferation phase of wound healing, and was
      associated with alpha-SMA in stress fibers formed by cultured dermal fibroblasts.
      CNN3 expression was post-transcriptionally regulated by tension, as demonstrated
      by disruption of actin filament organization under floating culture or
      blebbistatin treatment. CNN3 knockdown in primary fibroblasts impaired stress
      fiber formation, resulting in a phenotype of decreased cellular dynamics such as
      cell motility and contractile ability. These findings indicate that CNN3
      participates in actin stress fiber remodeling, which is required for cell
      motility and contraction of dermal fibroblasts in the wound healing process. 

PMID- 23545752
TI  - Detection of human herpesvirus 8 sequences in cutaneous cherry angiomas.
AB  - Cherry angiomas (CAs) are common vascular benign skin tumors, characterized by
      abnormal angiogenesis, whose etiology is still unclear and poorly studied. We
      investigated the presence of HHV8 in CAs due to virus ability of inducing
      neoangiogenesis in endothelial cells. A total of 29 patients were enrolled in a
      randomized, controlled, blinded analysis of skin specimens including various
      vascular lesions. All clinical samples were anonymized and analyzed by three
      different biomolecular assays to minimize the risk of false positive/negative
      results. Results showed that 53 % of eruptive CAs harbor HHV8 sequences, with the
      highest viral loads in samples derived from immunosuppressed patients. By
      contrast, no paucilesional CAs were positive for HHV8. Considering HHV8
      prevalence in the Mediterranean population (10-15 %), results obtained in
      eruptive CAs are significant and suggest for the first time a possible
      involvement of HHV8 in eruptive cherry angiomas development, particularly in the
      context of immunosuppression, similar to that recognized for major HHV8-induced
      pathologies. 

PMID- 23545753
TI  - Near-infrared room temperature emission from a novel class of Ru(II) heteroleptic
      complexes with quinonoid organometallic linker.
AB  - A novel class of luminescent octahedral ruthenium complexes 2-4 displaying a pi
      bonded quinonoid ligand is described. Remarkably, the presence of this
      organometallic ligand affects their UV-vis properties and transforms them into
      panchromatic absorbers. Furthermore, it turns on room temperature NIR emissions.

PMID- 23545754
TI  - Fluorescent photoremovable precursor (acridin-9-ylmethyl)ester: synthesis,
      photophysical, photochemical and biological applications.
AB  - A series of carboxylic acids including amino acids were protected as their
      corresponding fluorescent ester conjugates by coupling with an environment
      sensitive fluorophore 9-methylacridine. Photophysical properties of all the ester
      conjugates along with the protecting group have been investigated. Interestingly,
      the emission properties of the ester conjugates and 9-methylacridine were found
      to be highly sensitive to polarity, H-bonding and pH of the environment.
      Photolysis of all the ester conjugates was carried out using UV light above 360
      nm and it was found that in every case the corresponding carboxylic acids were
      released in high chemical yield. Further, intercalation and the preferred binding
      mode of acridine-9-methanol and its ester conjugates with DNA were studied. In
      vitro biological studies revealed that acridine-9-methanol has good
      biocompatibility, cellular uptake property and cell imaging ability.

PMID- 23545755
TI  - The management of gastrointestinal tract malignancies.
AB  - Surgery is the mainstay of treatment for many patients with malignancies of the
      gastrointestinal (GI) tract. The coordination of patient care and timing of
      surgical intervention require a multidisciplinary approach. It is not unusual for
      GI malignancies to be discovered in a hospital setting; patients with these
      malignancies are frequently admitted and discharged from nonsurgical services.
      Therefore, it is imperative that all physicians involved in the care of patients
      with GI malignancies have knowledge regarding the workup and surgical treatment
      of GI tract lesions. This article is a brief overview of the workup and surgical
      management of malignancies of the GI tract.

PMID- 23545756
TI  - A comparative trial of anti-factor Xa levels versus the activated partial
      thromboplastin time for heparin monitoring.
AB  - OBJECTIVE: To determine if laboratory monitoring of intravenous (IV)
      unfractionated heparin (UFH) using an anti-activated factor X (anti-factor Xa)
      assay, as opposed to the activated partial thromboplastin time (aPTT), would
      result in a higher percentage of results within the goal range, fewer monitoring
      tests, and fewer dose adjustments. METHODS: Retrospective, single-center, cohort
      study conducted at a community teaching hospital. A newly implemented deep vein
      thrombosis/pulmonary embolism treatment protocol, in which patients' doses of IV
      UFH were adjusted based on blood plasma anti-factor Xa level monitoring, was
      compared with a deep vein thrombosis/pulmonary embolism protocol, in which
      patients' IV UFH doses were adjusted based on monitoring with the blood plasma
      aPTT. We reviewed the medical records of 186 patients (88 managed by the anti
      factor Xa assay-based protocol and 98 managed by the aPTT-based protocol) to
      determine how often monitoring tests were within the goal range (aPTT, 75-110
      sec; anti-factor Xa, 0.3-0.7 U/mL), in addition to how many UFH dose adjustments
      and monitoring tests were required for each patient within a 24-hour period.
      RESULTS: In patients undergoing IV UFH therapy whose blood plasma was monitored
      with anti-factor Xa assay levels, as opposed to the aPTT, there was a higher
      percentage of UFH test results within the goal range (69% vs 41%; P < 0.0001),
      fewer monitoring tests were needed (2.08 vs 2.73; P = 0.001), and fewer dose
      adjustments were required per 24-hour period (0.62 vs 1.47; P < 0.0001).
      CONCLUSIONS: Use of an anti-factor Xa assay-based UFH-monitoring protocol
      resulted in a higher percentage of within-range blood plasma heparin monitoring
      tests, fewer monitoring tests for the patient to achieve blood plasma monitoring
      tests within goal range, and fewer dose adjustments compared with a protocol
      based on blood plasma monitoring using the aPTT.

PMID- 23545757
TI  - Can participation in mental and physical activity protect cognition in old age?:
      Comment on "The Mental Activity and eXercise (MAX) trial: a randomized controlled
      trial to enhance cognitive function in older adults".

PMID- 23545758
TI  - Determining the influence of type 1 diabetes on two common eating disorder
      questionnaires.
AB  - PURPOSE: This research evaluated the level of influence that having type 1
      diabetes (T1DM) has on responses to questions about food choices, eating
      concerns, dietary restraint, and others that are included on two widely used,
      validated eating disorder (ED) questionnaires and examined responses to these two
      questionnaires from patients with T1DM and an eating disorder (ED-T1DM) and an ED
      no-diabetes. METHOD: An expert panel rated each item on the Eating Disorders
      Examination Questionnaire (EDE-Q) and Eating Disorders Inventory, version 3 (EDI
      3) regarding T1DM level of influence on item interpretation. These questionnaires
      were completed by 2 matched samples (ED-T1DM, n = 48 and ED-no-diabetes, n = 96);
      responses were compared between the samples with particular attention to items of
      high T1DM influence. RESULTS: The expert panel identified that 50% (19/38) of the
      items on the EDE-Q and 6.6% (6/91) on the EDI-3 could be highly influenced by
      having T1DM. Before Bonferroni correction, the 2 groups responded statistically
      different on 9 out of 38 items on the EDE-Q and 27 out of 91 items on the EDI-3;
      generally responses were healthier for those with ED-T1DM than ED-no-diabetes. Of
      these items, on the EDE-Q, 5 were rated high T1DM influence and on the EDI-3, 3
      were rated high. CONCLUSION: Having T1DM influences responses on ED
      questionnaires developed for the general population. This influence may be
      greater when questionnaires focus on eating, weight, and shape and result in
      misinterpretation of total and subscale scores by even well-trained clinicians. A
      careful review of individual item responses by the treatment team is warranted.

PMID- 23545759
TI  - Continuous EEG monitoring in the pediatric and neonatal intensive care units.

PMID- 23545760
TI  - Continuous EEG monitoring in the neonatal intensive care unit.
AB  - Continuous EEG monitoring provides an opportunity to both accurately identify
      seizures and monitor the neurologic status of critically ill neonates in the
      intensive care unit. The incidence of seizures is higher in the neonatal period
      than at any other time in life. Seizures and abnormalities of EEG background are
      associated with significant risk of mortality and long-term neurodevelopmental
      morbidities. In the neonatal population the majority of seizures are not
      clinically evident and go undetected without EEG monitoring. We review the
      incidence and risk factors for neonatal seizures, and the utility of continuous
      EEG monitoring in the neonatal intensive care unit for seizure detection and for
      analysis of background to allow prognostication. We consider the role of
      amplitude-integrated EEG in the neonatal population. We consider the utility of
      continuous EEG for frequently encountered neurologic indications and discuss the
      outcome data and some new developments in continuous EEG monitoring.

PMID- 23545761
TI  - Diagnosing neonatal seizures and status epilepticus.
AB  - Continuous electroencephalographic (CEEG) monitoring is often applied in the
      Neonatal Intensive Care Unit to aid in the diagnosis and management of seizures.
      Neonatal seizures are particularly difficult to identify on the basis of clinical
      observation alone; diagnosis is greatly facilitated by CEEG monitoring. There is
      building evidence to suggest which neonates are at highest risk for seizures, and
      how CEEG can aid diagnosis. For the neurophysiologist, the unique features of
      neonatal seizures can distinguish them from nonictal patterns. These features
      include duration, location, morphology, and evolution. At the extreme, very
      frequent or prolonged neonatal seizures constitute status epilepticus. There is
      no consensus definition for neonatal status epilepticus, although the proposed
      criteria share some features. This article reviews available evidence to guide
      the application and interpretation of CEEG in the diagnosis of neonatal seizures
      and status epilepticus.

PMID- 23545762
TI  - EEG background patterns and prognostication of neonatal encephalopathy in the era
      of hypothermia.
AB  - Neonatal EEG can be useful for predicting outcome soon after acute hypoxia
      ischemia. There are techniques that can optimize the prognostic accuracy of EEG.
      Seizure medications and the time interval between hypoxia-ischemia and the EEG
      must be taken into account. Serial EEGs also improve the predictive ability of
      EEG.

PMID- 23545763
TI  - Utility of continuous EEG in children with acute traumatic brain injury.
AB  - Traumatic brain injury is a leading cause of childhood morbidity and mortality.
      The use of continuous EEG monitoring in the pediatric intensive care unit setting
      to aid in the management of acute traumatic brain injury is becoming more common,
      although practice does vary between institutions. This variability is a product
      of the relative paucity of data, particularly as it applies to prospective
      studies, in evaluating the use of continuous EEG after traumatic brain injury in
      the pediatric population. This review will summarize the current literature
      involving the utility of continuous EEG monitoring in children with acute
      traumatic brain injury, with focus on specific indications, impact on management,
      and prognostic value.

PMID- 23545765
TI  - Digital trend analysis in the pediatric and neonatal intensive care units.
AB  - Continuous EEG monitoring has become an essential modality for monitoring the
      central nervous system in the critically ill and has expanded beyond seizure
      detection. The massive amount of data generated and the associated logistical
      problems have limited the timely interpretation of these data. Digital trending
      analysis is a complimentary tool that creates a graphic display of the EEG data
      that may be visualized and interpreted at the bedside. This article reviews the
      use of digital trending analysis for pediatric and neonatal continuous EEG
      monitoring and its limitations.

PMID- 23545764
TI  - A review of long-term EEG monitoring in critically ill children with hypoxic
      ischemic encephalopathy, congenital heart disease, ECMO, and stroke.
AB  - Continuous EEG monitoring is being used with increasing frequency in critically
      ill children with hypoxic ischemic encephalopathy, congenital heart disease,
      stroke, and extracorporeal membrane oxygenation (ECMO). The primary indication
      for EEG monitoring is to identify electrographic seizures and electrographic
      status epilepticus, which have been associated with worse outcome in some
      populations. A secondary indication is to provide prognostic information. This
      review summarizes the available data regarding continuous EEG monitoring in
      critically ill children with special attention to hypoxic ischemic
      encephalopathy, congenital heart disease, stroke, and children undergoing ECMO.

PMID- 23545766
TI  - Pediatric ICU EEG monitoring: current resources and practice in the United States
      and Canada.
AB  - PURPOSE: To describe current continuous EEG monitoring (cEEG) utilization in
      critically ill children. METHODS: An online survey of pediatric neurologists from
      50 US and 11 Canadian institutions was conducted in August 2011. RESULTS:
      Responses were received from 58 of 61 (95%) surveyed institutions. Common cEEG
      indications are altered mental status after a seizure or status epilepticus
      (97%), altered mental status of unknown etiology (88%), or altered mental status
      with an acute primary neurologic condition (88%). The median number of patients
      undergoing cEEG per month per center increased from August 2010 to August 2011 (6
      to 10 per month in the United States; 2 to 3 per month in Canada). Few
      institutions have clinical pathways addressing cEEG use (31%). Physicians most
      commonly review cEEG twice per day (37%). There is variability regarding which
      services can order cEEG, the degree of neurology involvement, technologist
      availability, and whether technologists perform cEEG screening. CONCLUSIONS:
      Among the surveyed institutions, which included primarily large academic centers,
      cEEG use in pediatric intensive care units is increasing and is often considered
      indicated for children with altered mental status at risk for nonconvulsive
      seizures. However, there remains substantial variability in cEEG access and
      utilization among institutions.

PMID- 23545767
TI  - American clinical neurophysiology society standardized EEG terminology and
      categorization for the description of continuous EEG monitoring in neonates:
      report of the American Clinical Neurophysiology Society critical care monitoring
      committee.

PMID- 23545768
TI  - Inferring seizure frequency from brief EEG recordings.
AB  - Routine EEGs remain a cornerstone test in caring for people with epilepsy.
      Although rare, a self-limited seizure (clinical or electrographic only) may be
      observed during such brief EEGs. The implications of observing a seizure in this
      situation, especially with respect to inferring the underlying seizure frequency,
      are unclear. The issue is complicated by the inaccuracy of patient-reported
      estimations of seizure frequency. The treating clinician is often left to wonder
      whether the single seizure indicates very frequent seizures, or if it is of
      lesser significance. We applied standard concepts of probabilistic inference to a
      simple model of seizure incidence to provide some guidance for clinicians facing
      this situation. Our analysis establishes upper and lower bounds on the seizure
      rate implied by observing a single seizure during routine EEG. Not surprisingly,
      with additional information regarding the expected seizure rate, these bounds can
      be further constrained. This framework should aid the clinician in applying a
      more principled approach toward decision making in the setting of a single
      seizure on a routine EEG.

PMID- 23545769
TI  - EEG in silent small vessel disease: sLORETA mapping reveals cortical sources of
      vascular cognitive impairment no dementia in the default mode network.
AB  - INTRODUCTION: Vascular cognitive impairment, no dementia (vCIND) is a prevalent
      and potentially preventable disorder. Clinical presof the small vessel
      subcortical subtype may be insidious and difficult to diagnose in the initial
      stage. We investigated electroencephalographic sources of subcortical vCIND in
      comparison to amnesic multidomain mild cognitive impairment (amdMCI) to determine
      the additional diagnostic value of quantitative electroencephalograhy (EEG) in
      this setting. METHODS: Fifty-seven community residing patients with an uneventful
      central neurological history and first presentation of cognitive decline without
      dementia were included, 35 patients were diagnosed with vCIND and 22 with amdMCI.
      A cognitive control group, deliberately recruited from a cerebrovascular impaired
      cohort, consisted of cognitively healthy participants who experienced a fully
      recovered first ever transient ischemic attack (TIA) without clinical or magnetic
      resonance imaging evidence of stroke. From standard EEGs, the differences in
      standardized low-resolution brain electromagnetic tomography (sLORETA) sources
      were determined for the discrete frequency ranges 1-4 (delta), 4-8 (theta), 8
      10.5 (alpha1), 10.5-13 (alpha2), 13-22 (beta1), and 22-30 (beta2) Hz. RESULTS: In
      vCIND, a statistically significant decrease in parietooccipital alpha1 relative
      power current density compared with TIA and mild cognitive impairment patients
      was found. There was a significant decrease in frontal and parietooccipital beta1
      relative power current density in vCIND compared with TIA patients. A significant
      increase in (pre) frontal delta relative power current density in vCIND compared
      with amdMCI was found as well. In amdMCI, delta relative power current density
      was significantly increased in the core limbic system. DISCUSSION: Cortical
      sources of abnormal EEG activity in regions implicated in the default mode
      network are revealed by sLORETA at an early stage in vascular cognitive
      impairment. Mapping of parietooccipital alpha1, frontoparietooccipital beta1 and
      (pre) frontal delta loci in vCIND may reflect early executive and visuospatial
      dysfunction in this cohort. Standard EEG with sLORETA mapping might be an
      additional, noninvasive, and cost-effective tool in the diagnostic workup of
      patients presenting with a cognitive decline.

PMID- 23545770
TI  - Heightened beta EEG activity during nonrapid eye movement sleep in primary
      insomnia patients with reports of childhood maltreatment.
AB  - The present study explores the relationship between childhood maltreatment
      experiences and spectral power in high-frequency EEG activity during sleep in a
      sample of adults experiencing primary insomnia. Forty-five nontreated patients
      with primary insomnia spent three consecutive nights in the sleep laboratory,
      during which polysomnographic recordings were carried out. Nonrapid eye movement
      and rapid eye movement EEG data were analyzed using spectral analysis. In
      addition, each participant completed several self-report questionnaires assessing
      maltreatment in childhood and adolescence, current level of stress, and current
      depressivity. Insomnia patients with self-reported history of moderate to severe
      childhood maltreatment (MAL group; n = 25), as measured by the Childhood Trauma
      Questionnaire, were compared with insomnia patients without such a history (non
      MAL group; n = 20). The MAL group exhibited more absolute and relative beta 1 and
      beta 2 power in nonrapid eye movement sleep and more absolute beta 1 and beta 2
      activity in rapid eye movement sleep than the non-MAL group. Contrary to
      hypothesis, no group differences were found in gamma frequency band. The results
      suggest an association between history of childhood maltreatment and increased
      beta EEG activity particularly during nonrapid eye movement sleep in adult
      insomnia, what may reflect heightened psychophysiologic arousal during sleep.

PMID- 23545771
TI  - Electrophysiological features of taxane-induced polyneuropathy in patients with
      breast cancer.
AB  - Fifty-five patients with breast cancer were analyzed for electrophysiological
      characteristics of taxane-induced polyneuropathy. Based on the electrodiagnostic
      criteria, sensory motor polyneuropathy was found in 67% (37/55) of patients
      ranging between mild degree and moderate to severe degree. The polyneuropathy is
      predominantly axonal with three unique features: (1) frequent asymmetry, (2) high
      sural and radial sensory amplitude ratio in patients with mild polyneuropathy,
      and (3) slow conduction velocity seen only at the common entrapment sites, such
      as the carpal tunnel. The severity of polyneuropathy correlated positively with
      the cumulative dose received. Our study supports the clinical utility of
      electrodiagnostic study in both diagnosis and monitoring of taxane-induced
      polyneuropathy.

PMID- 23545772
TI  - Patient-centered care model in IONM: a review and commentary.
AB  - Both remote monitoring and nearby/available care models depend on waveform
      telemetry (a limited form of telemedicine) during intraoperative
      neurophysiological monitoring (IONM). These dominant models neither mandate
      preoperative patient contact nor assume co-practitioner collegiality. This review
      and commentary argues in favor of a routine, normative relationship between the
      patient and the IONM physician/professional (IONM-P). Similarly, normal collegial
      relations should be established and maintained over time between the IONM-P and
      fellow co-practitioners (the proceduralist and the anesthesiologist). This
      professional practice "upgrade" places the IONM-P in a much stronger bioethical
      position among peers (and third party reviewers of the field and its practices).
      This "upgrade" also improves the likelihood that correct context-driven decisions
      will be made by the co-practitioners (IONM-P, proceduralist, and
      anesthesiologist) during complex multimodality monitoring. Most current models of
      IONM can be accommodated by readily available telemedicine-mediated
      videoconferencing. Several lines of argument are used to support this "patient
      centered care model" of IONM.

PMID- 23545773
TI  - Interrater reliability of intensive care unit electroencephalogram revised
      terminology: pitfalls and challenges of using kappa value.

PMID- 23545774
TI  - In reply.

PMID- 23545775
TI  - Typical versus atypical triphasic morphology waveforms.

PMID- 23545776
TI  - Typical versus atypical triphasic waves.

PMID- 23545777
TI  - Assembly-driven synthesis of hybrid molecular capsules controlled by chiral
      sorting.
AB  - Chiral capsules with polar interiors (reversed capsules) undergo heterochiral
      sorting and exhibit positive mutalism - both hemispheres mutually benefit from
      the association. This feature can be coupled with partial reversibility of the
      formation reaction and utilized to amplify synthesis of hybrid capsules made of
      hemispheres that cannot be formed independently.

PMID- 23545778
TI  - Systematic breakdown of Amontons' law of friction for an elastic object locally
      obeying Amontons' law.
AB  - In many sliding systems consisting of solid object on a solid substrate under dry
      condition, the friction force does not depend on the apparent contact area and is
      proportional to the loading force. This behaviour is called Amontons' law and
      indicates that the friction coefficient, or the ratio of the friction force to
      the loading force, is constant. Here, however, using numerical and analytical
      methods, we show that Amontons' law breaks down systematically under certain
      conditions for an elastic object experiencing a friction force that locally obeys
      Amontons' law. The macroscopic static friction coefficient, which corresponds to
      the onset of bulk sliding of the object, decreases as pressure or system length
      increases. This decrease results from precursor slips before the onset of bulk
      sliding, and is consistent with the results of certain previous experiments. The
      mechanisms for these behaviours are clarified. These results will provide new
      insight into controlling friction.

PMID- 23545779
TI  - Generation of gene-modified mice via Cas9/RNA-mediated gene targeting.

PMID- 23545781
TI  - Electrical stimulation enhances peripheral nerve regeneration after crush injury
      in rats.
AB  - Injured peripheral nerves have the ability to regenerate; however, there is
      conflicting evidence with regard to whether electrical stimulation (ES)
      accelerates or hinders neural regeneration. To study the effect of ES on
      peripheral nerve regeneration following nerve crush injury, 54 Wistar rats were
      randomly divided into three groups (n=18/group); the control, crush and crush+ES
      group. Four weeks after surgery, the sciatic functional index (SFI), compound
      muscle action potential (CMAP) conduction velocity and amplitude in the
      regenerated nerve, nerve histomorphometry, and levels of myelin protein zero (P0)
      mRNA and protein at the crush site were assessed. The rats exposed to crush+ES
      had a significantly increased CMAP conduction velocity, enhanced myelin sheath
      thickness and increased P0 mRNA and protein levels compared with the rats exposed
      to crush alone. However, the CMAP amplitude and axonal diameter were similar in
      the crush and crush+ES rats. Findings of this study demonstrated that the
      application of ES (3 V, 0.1 ms, 20 Hz, 1 h) immediately after nerve injury
      accelerates remyelination and may provide a therapeutic clinical strategy.

PMID- 23545782
TI  - Recovering degraded quasi-solid-state dye-sensitized solar cells by applying
      electrical pulses.
AB  - We discovered a method of applying a forward pulsed bias to recover the degraded
      quasi-solid-state dye-sensitized solar cells (DSSCs). Up to 30.7% of the power
      conversion efficiency (eta) of a degraded poly(vinylidene fluoride) (PVDF) based
      DSSC was recovered by a double-pulse. The recovered eta remained higher than that
      before the double-pulse treatment for at least 28 days. It is deduced that the
      blocking of ion-transport channels in the quasi-solid-state electrolyte causes
      degradation of the DSSCs. This study will shed light on the efficiency
      enhancement and long-term stability of quasi-solid-state DSSCs.

PMID- 23545783
TI  - Molecularly imprinted polymers prepared using protein-conjugated cleavable
      monomers followed by site-specific post-imprinting introduction of fluorescent
      reporter molecules.
AB  - Molecularly imprinted polymers were prepared using a protein-conjugated disulfide
      cleavable monomer. After removing the protein by disulfide reduction, a thiol
      reactive fluorophore was introduced into the thiol residue located only inside
      the imprinted cavity, resulting in specific transduction of the binding events
      into fluorescence spectral change. 

PMID- 23545780
TI  - IFNbeta/TNFalpha synergism induces a non-canonical STAT2/IRF9-dependent pathway
      triggering a novel DUOX2 NADPH oxidase-mediated airway antiviral response.
AB  - Airway epithelial cells are key initial innate immune responders in the fight
      against respiratory viruses, primarily via the secretion of antiviral and
      proinflammatory cytokines that act in an autocrine/paracrine fashion to trigger
      the establishment of an antiviral state. It is currently thought that the early
      antiviral state in airway epithelial cells primarily relies on IFNbeta secretion
      and the subsequent activation of the interferon-stimulated gene factor 3 (ISGF3)
      transcription factor complex, composed of STAT1, STAT2 and IRF9, which regulates
      the expression of a panoply of interferon-stimulated genes encoding proteins with
      antiviral activities. However, the specific pathways engaged by the synergistic
      action of different cytokines during viral infections, and the resulting
      physiological outcomes are still ill-defined. Here, we unveil a novel delayed
      antiviral response in the airways, which is initiated by the synergistic
      autocrine/paracrine action of IFNbeta and TNFalpha, and signals through a non
      canonical STAT2- and IRF9-dependent, but STAT1-independent cascade. This pathway
      ultimately leads to the late induction of the DUOX2 NADPH oxidase expression.
      Importantly, our study uncovers that the development of the antiviral state
      relies on DUOX2-dependent H2O2 production. Key antiviral pathways are often
      targeted by evasion strategies evolved by various pathogenic viruses. In this
      regard, the importance of the novel DUOX2-dependent antiviral pathway is further
      underlined by the observation that the human respiratory syncytial virus is able
      to subvert DUOX2 induction.

PMID- 23545784
TI  - Experiencing community: perspectives of individuals diagnosed as having serious
      mental illness.
AB  - OBJECTIVE: Community integration is recognized as a crucial component of recovery
      from serious mental illness. Although the construct of community integration can
      be measured with structured instruments, little is known about the subjective and
      experiential meaning of community and community involvement for persons with
      serious mental illness. METHODS: In 2010, 30 individuals with serious mental
      illness treated in two public mental health clinics completed semistructured
      interviews that elicited the places and people that they associate with the
      experience of community and the larger meaning of community in their lives.
      RESULTS: Participants described four experiences as integral to their concepts of
      community: receiving help, minimizing risk, avoiding stigma, and giving back.
      Participants looked for communities that provide reliable support, and they
      described the need to manage community contact in order to protect themselves and
      others from their symptoms and from discrimination. Most participants experienced
      communities centered on mental health treatment or mentally ill peers as
      providing opportunities for positive engagement. CONCLUSIONS: The experience of
      having a serious mental illness shapes preferences for and perceptions of
      community in pervasive ways. Participants described community involvement not as
      a means to move away from illness experiences and identities but as a process
      that is substantially influenced by them. Mental health communities may help
      individuals with serious mental illness to both manage their illness and
      recognize and enjoy a sense of community. The findings indicate the need for
      further research on the relationship between community integration and outcome in
      serious mental illness.

PMID- 23545787
TI  - When addiction co-occurs with traumatic brain injury.

PMID- 23545788
TI  - Fetal and sociocultural environments and autism.

PMID- 23545785
TI  - Christia vespertilionis plant extracts as novel antiproliferative agent against
      human neuroendocrine tumor cells.
AB  - Neuroendocrine tumors respond poorly to radiation and conventional chemotherapy,
      hence surgical removal of the neoplastic tissue is still the most effective way
      of treatment. In an attempt to find new therapeutic plant extracts of Christia
      vespertilionis (CV) their antitumor potential in human medullary thyroid
      carcinoma (MTC) and human small intestinal neuroendocrine tumor (SI-NET) cell
      lines were tested. Proliferation and viability were analyzed using cell counting
      and WST-1 assay. Apoptosis was determined by microscopy, luminescence assays for
      caspases 3/7, and expression studies of apoptosis-related genes. CV extracts
      showed antiproliferative and proapoptotic effects in all MTC and SI-NET cell
      lines, whereby high growth inhibition was observed by treatment with the
      ethylacetate-extracts (CV-45) in tumor cell lines but not in normal human
      fibroblasts. Furthermore CV-45 treatment resulted in alterations of gene
      expression of PDCD5, MTDH and TNFRSF10b in MTC as well as in SI-NET cells. The
      results indicate that Christia vespertilionis could serve as an anticancer
      therapeutic for treatment of neuroendocrine tumors.

PMID- 23545789
TI  - Reduced binding to nicotinic receptors after nicotine vaccination: is the effect
      big enough to be clinically meaningful?

PMID- 23545790
TI  - Should mental health interventions be locally grown or factory-farmed?

PMID- 23545791
TI  - White blood cell monitoring during long-term clozapine treatment.
AB  - Late-onset agranulocytosis is rare during treatment with clozapine, especially in
      monotherapy. The authors describe a case of agranulocytosis that emerged after 19
      years of continuous clozapine monotherapy. The discovery of the agranulocytosis
      was due to the lifelong white blood cell counts that are now required for
      clozapine treatment. Despite the fact that this requirement probably saved the
      life of this patient, this monitoring is not evidence-based because the incidence
      of agranulocytosis does not exceed that of conventional antipsychotic drugs, for
      which no such requirement exists. For mentally competent and adequately informed
      patients, the Netherlands Clozapine Collaboration Group now permits quarterly
      monitoring after the first 6 months of clozapine treatment.

PMID- 23545792
TI  - Anorexia mirabilis: the practice of fasting by Saint Catherine of Siena in the
      late Middle Ages.

PMID- 23545793
TI  - Deviance in fetal growth and risk of autism spectrum disorder.
AB  - OBJECTIVE: Understanding the relationship between fetal growth and autism
      spectrum disorder (ASD) is likely to advance the search for genetic and
      nongenetic causes of ASD. The authors explored the associations between fetal
      growth, gestational age, and ASD with and without comorbid intellectual
      disability in a Scandinavian study population. METHOD: The authors conducted a
      matched nested case-control study within the Stockholm Youth Cohort that included
      all children ages 0-17 who resided in Stockholm County from 2001 to 2007
      (N=589,114). The authors identified 4,283 children with ASD: 1,755 with
      intellectual disability and 2,528 without, and they selected 36,588 age- and sex
      matched comparison subjects. ASD case subjects were ascertained from unique
      identifiers assigned to all Swedish residents and linkage with official registers
      covering all pathways of assessment or care of ASD in Stockholm County. The
      authors calculated z scores of deviance in fetal growth from a reference curve
      using records from the national Swedish Medical Birth Registry, which included
      ultrasound dating of gestational age as well as birth weight. Crude and adjusted
      odds ratios for ASD, ASD with intellectual disability, and ASD without
      intellectual disability were the main outcome measures. RESULTS: ASD risk
      increased with fetal growth 1.50 standard deviations below and >2.00 standard
      deviations above the mean for gestational age; the greatest risk was for fetal
      growth that was less than 2.00 standard deviations below the mean (adjusted odds
      ratio=1.70; 95% CI=1.44-2.01) or greater than 2.00 standard deviations above the
      mean (adjusted odds ratio=1.50; 95% CI=1.27-1.77). The same overall pattern was
      observed for ASD with and without intellectual disabilities. However, poor fetal
      growth (i.e., growth below the mean) was more strongly associated with ASD with
      intellectual disabilities than without. Regardless of fetal growth, preterm birth
      increased ASD risk. CONCLUSIONS: Deviance in fetal growth at either
      distributional extreme may be a significant antecedent to the development of ASD
      through genetic and/or nongenetic mechanisms.

PMID- 23545794
TI  - Effects of pharmacologically induced hypogonadism on mood and behavior in healthy
      young women.
AB  - OBJECTIVE: The relationship between depression and estrogen withdrawal remains
      controversial. The authors examined the effects of gonadotropin-releasing hormone
      agonist-induced ovarian suppression on mood, sleep, sexual function, and
      nighttime hot flushes. They focused on whether participating women experienced
      clinically significant depressive symptoms and whether specific symptoms
      associated with hypogonadism (nighttime hot flushes and disturbed sleep)
      increased susceptibility to depression. METHOD: Participants were 72 healthy
      premenopausal women, ages 19-52 years, with no current or past axis I psychiatric
      diagnosis or gynecological or other medical illness. After 2 months of baseline
      screening, women received monthly injections of leuprolide acetate (3.75 mg) for
      2-3 months. Outcomes were measured using the Beck depression inventory (BDI) and
      a daily rating scale measuring the severity of several affective and behavioral
      symptoms. Data were analyzed by repeated-measures analysis of variance using PROC
      MIXED (for mixed models). RESULTS: BDI scores >=10 were reported in four of the
      72 women (5.6%). Relative to baseline, induced hypogonadism was associated with
      significantly decreased sexual interest, disturbed sleep, and more severe
      nighttime hot flushes, but no significant change in any mood-related symptom
      score. Hot flush severity was significantly correlated with disturbed sleep.
      CONCLUSIONS: These data demonstrate that clinically significant depressive
      symptoms were rare accompaniments of short-term estradiol withdrawal and induced
      hypogonadism in healthy premenopausal women. Additionally, neither nighttime hot
      flushes nor disturbed sleep were sufficient to cause depressive symptoms in
      hypogonadal women.

PMID- 23545795
TI  - The DSM-5 field trials and reliability of alcohol use disorder.

PMID- 23545796
TI  - Response to Hasin et al. letter.

PMID- 23545798
TI  - Response to Ritvo and Ritvo letter.

PMID- 23545799
TI  - Treatment course with antidepressant therapy in late-life depression.

PMID- 23545801
TI  - Commentary on the application of DSM-5 criteria for autism spectrum disorder.

PMID- 23545802
TI  - Response to Irion et al. letter.

PMID- 23545803
TI  - Adrenergic receptor gene variation and selective norepinephrine reuptake
      inhibitors.

PMID- 23545805
TI  - The disintegrin domain of ADAM17 antagonises fibroblast-carcinoma cell
      interactions.
AB  - The malignant phenotype of carcinoma cells depends on their ability to invade
      into their microenvironment promoting metastasis. Therefore, carcinoma cells
      overexpress many proteins, including A disintegrin and metalloproteases (ADAMs).
      ADAM17 is expressed by different cancer cell lines and possesses adhesive as well
      as enzymatic activities. To address the adhesive properties in tumour progression
      the recombinantly expressed soluble disintegrin domain of ADAM17 was employed.
      Fibroblasts and carcinoma cells adhere to the immobilized disintegrin domain.
      Additionally, the soluble disintegrin domain impaired fibroblast-carcinoma cell
      interactions and increased the shedding activity of ADAM17. Silencing of ADAM17
      in fibroblasts or in carcinoma cells decreases cell-cell interaction between
      these cells. In summary, our results show that the adhesive properties of ADAM17
      are mediated by its disintegrin domain and enables carcinoma cells to interact
      with their microenvironment.

PMID- 23545806
TI  - In vitro metabolism and pharmacokinetic studies on methylone.
AB  - Abuse of the stimulant designer drug methylone (methylenedioxymethcathinone) has
      been documented in most parts of the world. As with many of the new designer
      drugs that continuously appear in the illicit drug market, little is known about
      the pharmacokinetics of methylone. Using in vitro studies, CYP2D6 was determined
      to be the primary enzyme that metabolizes methylone, with minor contributions
      from CYP1A2, CYP2B6, and CYP2C19. The major metabolite was identified as
      dihydroxymethcathinone, and the minor metabolites were N-hydroxy-methylone, nor
      methylone, and dihydro-methylone. Measuring the formation of the major
      metabolite, biphasic Michaelis-Menten kinetic parameters were determined:
      V(max,1) = 0.046 +/- 0.005 (S.E.) nmol/min/mg protein, K(m,1) = 19.0 +/- 4.2 MUM,
      V(max,2) = 0.22 +/- 0.04 nmol/min/mg protein, and K(m,2) = 1953 +/- 761 MUM; the
      low-capacity and high-affinity contribution was assigned to the activity of
      CYP2D6. Additionally, a time-dependent loss of CYP2D6 activity was observed when
      the enzyme was preincubated with methylone, reaching a maximum rate of
      inactivation at high methylone concentrations, indicating that methylone is a
      mechanism-based inhibitor of CYP2D6. The inactivation parameters were determined
      to be K(I) = 15.1 +/- 3.4 (S.E.) MUM and k(inact) = 0.075 +/- 0.005 minute(-1).

PMID- 23545807
TI  - Population pharmacokinetic analysis of daikenchuto, a traditional Japanese
      medicine (Kampo) in Japanese and US health volunteers.
AB  - We constructed population pharmacokinetic (PK) models for the five constituents
      of daikenchuto (DKT), a traditional Japanese herbal medicine. Data were collected
      from two randomized PK studies conducted in Japan and the United States.
      Participants received single oral doses of 2.5 g, 5 g, and 10 g of DKT. The
      plasma concentrations of five DKT constituents--hydroxy-alpha-sanshool (HAS),
      hydroxyl-beta-sanshool (HBS), 6-shogaol (6S), 10-shogaol (10S), and ginsenoside
      Rb1 (GRB1)--were determined by liquid chromatography-tandem mass spectrometry. A
      total of 1859 samples from 55 participants (US, n = 36; Japanese, n = 19) were
      included in the analysis. Population PK models of HAS, HBS, 6S, and 10S were best
      described by a one or two-compartment model with a bolus input. On the other
      hand, the model of GRB1 was best described by a one-compartment model with
      nonlinear extravascular input. Among the covariates evaluated, body mass index
      (BMI) and age were found to influence oral clearance (CL/F) and volume of
      distribution (Vd/F) for HAS and HBS, respectively. The influence of body weight
      on CL/F and Vd/F for 6S was demonstrated. Marked differences were observed in
      mean plasma concentrations of HAS and HBS between Japanese and US participants.
      However, the simulation results indicated that the difference in plasma
      concentrations may be attributed to the difference in demographic factors such as
      BMI, body weight, and age, whereas ethnic difference between the Japanese and US
      participants was considered minimal.

PMID- 23545808
TI  - Acid loading stimulates rat glomerular mesangial cells proliferation through
      Na(+)-H (+) exchanger isoform 1 (NHE1)-dependent pathway.
AB  - The role of metabolic acidosis in the progression of chronic kidney disease (CKD)
      remains unclear. The aim of the present study was to investigate the direct
      effects of acid loading on the proliferation of rat glomerular mesangial cells
      (GMCs) in vitro and the possible role of sodium-hydrogen ion exchanger isoform 1
      (NHE1). Rat GMCs were treated with acidic medium as acid loading. Growth and
      proliferation of GMCs was studied by the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay, thymidine ((3)H-TdR) incorporation, and
      flow cytometry. NHE1 protein expression and activity were quantified by Western
      blot and dual wavelength epifluorescent illumination with 2',7'-bis-(2
      carboxyethyl)-5(6)-carboxyfluorescein, respectively. 5-(N,N-dimethyl) amiloride
      hydrochloride (DMA), a specific inhibitor of NHE1, was used to investigate the
      possible involvement of NHE1 in the proliferation of GMCs. The MTT assay, (3)H
      TdR incorporation, and cell cycle distribution analysis indicated that acid
      loading stimulated the proliferation of GMCs. Acid loading increased NHE1
      activity, but had no effects on NHE1 expression at the protein level. The effects
      of acid loading on the proliferation of GMCs were inhibited by DMA. Acid loading
      induced GMC proliferation through NHE1-dependent pathways. Our findings may
      contribute to the understanding of metabolic acidosis in the progression of CKD.

PMID- 23545811
TI  - Small renal masses: Jury still out on robotic partial nephrectomy.

PMID- 23545810
TI  - Incontinence: OnabotulinumtoxinA safer than abobotulinumtoxinA for OAB.

PMID- 23545812
TI  - Infection: Trichomonas infection influences the vaginal microbiome.

PMID- 23545814
TI  - Small renal masses: Stable long-term renal function after partial nephrectomy in
      solitary kidney.

PMID- 23545813
TI  - Potential biofluid markers and treatment targets for renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the 13th most common cancer in the world and one of
      the few cancers for which incidence is increasing. This disease is generally
      asymptomatic at an early stage and is highly metastatic. Frequently discovered by
      physicians in the process of working up other diseases such as acute kidney
      injury, RCC is often discovered in an advanced form and many patients have
      metastases at the time of diagnosis. Given that life expectancy with currently
      approved therapies for metastatic RCC is approximately 1-2 years, biomarkers for
      RCC that will enable early detection are urgently needed. Although it is unlikely
      that highly sensitive and specific biomarkers will be identified in the near
      future that are useful for screening the general population, a noninvasive marker
      or set of markers could soon be used in general medicine, nephrology, and urology
      clinics to screen patients at increased risk of RCC. In addition to the ongoing
      need for RCC biomarkers, the frequent resistance reported with currently
      available targeted therapies makes the identification of new therapeutic targets
      similarly important. Many promising leads for new targeted therapies have come to
      light; some of these therapies are in clinical trials and others are still being
      evaluated in the laboratory.

PMID- 23545815
TI  - Small renal masses: the effect of illness uncertainty during active surveillance.

PMID- 23545816
TI  - [Clinical analysis of modified technique for pectus bar removal after Nuss
      procedure].
AB  - OBJECTIVE: To evaluate the safety and efficacy of modified technique for removing
      Nuss bar after Nuss procedure. METHODS: We reviewed 186 patients undergoing bar
      removal after repair of pectus excavatum with Nuss procedure at our institution
      from December 2008 to February 2012. All patients had unilateral incision
      (metallic stabilizers have been used on one side in all patients). Under general
      anesthesia with single lumen tracheal tube or laryngeal mask, with the patient
      lying down in supine position, the bar was pulled out along the thoracic wall
      without overturning or straightening. RESULTS: Totally 132 patients (71.0%) had
      the bar removed 2 years after the Nuss procedure, 1 (0.5%) removed within 1 year
      and 53 (28.5%) removed over 2 and half years. The operation time for bar removal
      was 9-20 (13.1 +/- 3.4) min, and the operative blood loss was 3-20 (5.2 +/- 2.7)
      mL. There was no hemorrhage. Three patients (1.6%) developed mild pneumothorax
      and none showed infection of incision after the operation. All patients were
      discharged 1 day after the surgery and followed up for 4-48 (21.4 +/- 6.8)
      months. Recurrence was found in the one who which had the bar removed within 1
      year (0.5%). CONCLUSION: With modified procedures, Nuss bar can be easily and
      safely removed 2 years or longer after the Nuss operation. After removing the
      metallic stabilizer, the bar should be turned and then pulled out along the
      original surgical incision without bending or turning.

PMID- 23545817
TI  - Efficacy of oral fludarabine in patients with chronic lymphocytic leukemia/small
      lymphocytic lymphoma.
AB  - OBJECTIVE: To investigate the efficacy and safety of oral fludarabine in patients
      with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). METHODS:
      The patients received oral fludarabine 40 mg/(m2.d) for 5 consecutive days, each
      treatment lasting 4 weeks. The efficacy was assessed with National Comprehensive
      Cancer Network (NCCN) criteria for response. RESULTS: Twenty-two patients
      received the treatment, a median of 4 cycles per patient. The rate of complete
      response (CR), partial response (PR), and overall response (OR) was 40.9% (9/22),
      45.5% (10/22), and 86.4% (19/22), respectively. Among the 17 previously untreated
      patients, 7 (41.2%) achieved CR and 8 (47.0%) achieved PR. Two of the 5 pre
      treated patients achieved CR and the other 2 achieved PR. During a median
      observation of 24 months, the overall survival rate was 81.8%. The main adverse
      reactions were myelosuppression and infection. Grade 1 to 3 granulocytopenia was
      found in 7 (31.8%) patients, and infection in 3 (13.6%) patients. Nonhematologic
      toxicity was mild. All the adverse reactions were reversible. CONCLUSION: The
      oral fludarabine is effective, safe, and well-tolerated in the patients with CLL/
      SLL.

PMID- 23545818
TI  - [Expression of HPV16 E6 protein in nonneoplastic epithelial disorder of the vulva
      and squamous cell carcinoma of the vulva].
AB  - OBJECTIVE: To investigate the expression of high risk human papilloma virus (HPV)
      16-E6 protein in non-neoplastic epithelial disorders of the vulva (NNEDV) and
      squamous cell carcinoma of the vulva (VSCC), and to explore whether HPV16-E6
      protein is the etiological factor in NNEDV and its correlation with squamous cell
      carcinoma of the vulvae. METHODS: We detected HPV16-E6 protein expression in 15
      normal vulvae cases, 40 NNEDV cases and 45 VSCC cases by immunohistochemistry SP
      method. RESULTS: The positive rate of HPV16-E6 in different vulva tissues: was 0%
      in the normal vulva, 30% in NNEDV and 66.67% in VSCC, respectively. The overall
      positive rate and two two comparison had statistical significance. In the NNEDV
      group, the positive rate of squamous hyperplasia type and lichen sclerosus type
      was 35% and 25%, respectively, with no statistical significance (P>0.05), but
      higher than that in the normal vulva skin group (P<0.05) and lower than that in
      the VSCC group (P<0.05). The positive rate of HPV16-E6 in VSCC was 66. 67%. The
      positive rate increased with the clinical stage. The positive rate between Phase
      I and Phase II, and that between Phase I and Phase III had statistical
      significance (P<0.017), but that between Phase II and Phase III had no
      statistical significance (P>0.017). The positive rate gradually decreased with
      the tumor differentiation. The difference in well-differentiated and poorly
      differentiated, moderately and poorly differentiated had statistical significance
      (P<0.017), but that of well-differentiated and moderately differentiated had no
      statistical significance (P>0.017). The positive rate of lymph node metastasis
      VSCC was significantly higher than that of non-lymph node metastasis VSCC
      (P<0.05). CONCLUSION: HPV infection may be an etiological factor for NNEDV. The
      rise of HPV16-E6 positive rate may be related to the occurrence and development
      of vulvar squamous cell carcinoma.

PMID- 23545819
TI  - [High field magnetic resonance background suppression diffusion imaging in the
      diagnosis of liver foci of space occupying lesion].
AB  - OBJECTIVE: To explore the diagnostic value of the 3.0T magnetic resonance liver
      diffusion weighted imaging with background suppression (DWIBS) in liver foci of
      space occupying lesion. METHODS: A total of 43 cases of liver bureau stove perch
      pathological change were included: 15 were hepatocellular carcinoma (HCC) with 24
      lesions; 7 were liver metastatic tumor with 13 lesions; 10 were liver hemangioma
      with 12 lesions; and 11 liver cyst with 20 lesions. After taking the conventional
      T1WI and T2WI sequence, the magnetic resonance background suppression diffusion
      imaging technology (diffusion weighted imaging with background suppression,
      DWIBS) was applied, following the dynamic enhanced scan. With the MRI to DWIBS
      workstation for classifying positron emission computed tomography (PET)
      processing, the T2WI diagram and dynamic enhanced diagram were compared
      respectively for the 3 sequences of lesion detection rate, T2WI, and DWIBS, to
      enhance the delay time between the two joint and combined lesion detection rate.
      With the MRI workstation software scanning image generation ADC diagram, the ADC
      values were measured for liver cancer, liver metastatic tumor, liver hemangioma
      and liver cysts. RESULTS: The 3 sequences of detection rates of the T2WI, DWIBS
      and enhanced delay period T1WI were 91.3%, 94.2%, and 95.6%. The detection rate
      of DWIBS plus T2WI was 92.7%; that of T2WI plus enhanced delay time was 94.9%,
      and that of DWIBS plus enhanced delay time was 96.3%, with the rate of DWIBS plus
      enhanced delay period obviously higher than that of the DWIBS plus T2WI (P<0.05).
      The ADC value of the benign liver tumor was obviously higher than that of the
      malignant tumors: hepatic cyst (2.614 +/- 0.57)*10-3 mm2/s, liver hemangioma
      (2.055 +/- 0.21)*10-3 mm2/s, metastatic carcinoma (1.374 +/- 0.32)* 10-3 mm2/s,
      and liver cancer (1.287 +/- 0.14)*10-3 mm2/s. Except for the liver cancer and the
      liver metastatic tumor, there was significant difference between the other groups
      (P<0.05). CONCLUSION: Combing the DWIBS technology, the PET-like images and the
      ADC value acquired, the combined enhanced sequences could further facilitate the
      demonstration of the liver foci of space occupying lesion, the accuracy of
      identification and diagnosis of the liver foci of space occupying lesion.

PMID- 23545820
TI  - [Magnetic resonance imaging for active ankylosing spondylitis].
AB  - OBJECTIVE: To diagnoze active ankylosing spondylitis (AAS) by magnetic resonance
      imaging (MRI). METHODS: MRI of the sacroiliac joint (SIJ) was performed on 48
      patients who were clinically diagnosed as probable AS without radiologic evidence
      of sacroiliitis. Among them 21 were diagnozed as active sacroiliitis with MRI,
      whose examination was terminated; 27 whose MRI of SIJ did not diagnoze as active
      sacroiliitis were performed MRI in the thoracic spine. The diagnostic criteria of
      MRI for AAS of SIJ and/or the thoracic spine were fomulated by consulting
      documents. The definite diagnosis of AAS was finally made after follow-up for
      half a year. The sensitivity and specificity of the MRI of SIJ and/or MRI of
      thoracic spine were assessed. RESULTS: In the 48 patients without radiologic
      evidence of sacroiliitis, 38 were finally diagnosed as AAS, with established
      consensus criteria as reference standard. The sensitivity and specificity of the
      MRI of SIJ were 52.6% and 90.0%, and for the MRI of SIJ and/or the MRI of the
      thoracic spine 76.3% and 90.0%, respectively. CONCLUSION: Clinically probable AS
      without MRI evidence of sacroiliitis, MRI of the thoracic spine can increase the
      sensitivity of AAS diagnosis.

PMID- 23545821
TI  - [Pathogen distribution and antibiotic resistance for hospital aquired pneumonia
      in respiratory medicine intensive care unit].
AB  - OBJECTIVE: To investigate the change of pathogen distribution and antibiotic
      resistance of pathogens isolated from in-patients with hospital acquired
      pneumonia (HAP) in the Department of Respiratory Medicine Intensive Care Unit
      (RICU) of Xiangya Hospital in 2005 and in 2011, and to provide reasonable anti
      infectious strategy. METHODS: The positive susceptibility test of sputum
      (bronchial secretions) culture was done in patients with HAP in RICU of Xiangya
      Hospital in 2005 and in 2011, and the distribution feature and antibiotic
      resistance were compared. RESULTS: 1) In the two years, the main pathogen in HAP
      patients was Gram negative bacteria (infection rate was 68.07% and 65.21% in 2005
      and in2011 respectively). The primary pathogenic bacteria were changed, and
      Acinetobacter baumanii became the most common Gram negative bacterium which
      replaced Pseudomonas aeruginosa, with infection rate 6.81% in 2005 to 40.87% in
      2011. The infection rate of Pseudomonas aeruginosa reduced from 20.42% in 2005 to
      15.60% in 2011. Haemophilus influenzae was rare. Staphylococcus aureus became the
      primary Gram positive bacteria, and its infection rate increased from 1.57% in
      2005 to 4.83% in 2011, all of which were methicillin-resistant Staphylococcus
      aureus (MRSA). Saccharomyces albicans' positive culture rate increased
      significantly. 2) Compared with in 2005, the antibiotic resistance of pathogen
      isolated from the HAP pationts changed a lot in 2011: increased antibiotic
      resistance rate and decreased sensitivity to many antibiotics. Pseudomonas
      aeruginosa was only relatively susceptible to meropenem, cefoperazone sulbactam,
      ceftazidime, cefpodoxime, and andamicaxin in 2011. The resistance rate of
      Pseudomonas aeruginosa to levofloxacin, cyclopropane, amicacin, gentamicin,
      meropenem, cematrixone, and piperacilintazobactam increased obviously (P<0.05).
      Compared with 2005, Acinetobacter baumanii was totally susceptible to polymyxin
      and relatively susceptible to sulbactam, but it was almost completely resistant
      to Aminoglycoside antibiotics in 2011, with significant difference (P<0.01).
      CONCLUSION: The main pathogen of HAP patients in RICU was Gram negative bacteria,
      with increased infection rate of Staphylococcus aureus and fungus. There is
      change pathogen distribution and antibiotic resistance, and the clinical initial
      experimental antibiotic therapy may be influenced. It is important to use
      antibiotics more rationally to delay the antibiotic resistance.

PMID- 23545822
TI  - [Clinical analysis of 45 patients with intracranial germinoma treated by
      radiotherapy].
AB  - OBJECTIVE: To report the prospective efficacy of 45 patients intracranial
      germinoma treated by radiotherapy and discuss its treatment. METHODS: From
      February 1998 to October 2007, a total of 45 intracranial germinoma patients were
      performed radiotherapy, including 15 combined chemotherapy in the Department of
      Oncology. Of them 23 were pathologically diagnosed while 22 cases were clinical
      diagnosed. Life table method showed the 5-year and 10-year survival rate.
      RESULTS: Forty patients were followed-up. Most symptoms of the patients were
      significantly reduced or disappeared completely. The 5-year and 10-year survival
      rate of all patients were 84% and 74%. CONCLUSION: Radiotherapy is the main
      treatment for intracranial germinoma. Craniospinal irradiation, whole brain
      irradiation and partial brain irradiation are the main treatments. Radiotherapy
      combined with chemotherapy, which can reduce the radiation range and dose will be
      the trend.

PMID- 23545823
TI  - [Curative effect of arthroscopic suture anchor fixation on shoulder bankart
      injury].
AB  - OBJECTIVE: To determine the curative effect of arthroscopic suture anchor
      fixation on shoulder bankart injury. METHODS: Sixteen patients with shoulder
      recurrent dislocation and diagnosed bankart injury were treated with suture
      anchor fixed by shoulder arthroscopy. Both shoulders of the patients had X-ray,
      MRI, physical examination before the operation. Suture anchors were used to fix
      the lesion labrum by shoulder arthroscopy. University of California at Los
      Angeles (UCLA) score and visual analogue scale (VAS) score were adopted for the
      final evaluation at the latest follow-up. RESULTS: All patients were followed for
      a period of 25 (7-68) months. At the latest follow-up, no redislocation and
      instability occured. The pre- and post-operation UCLA score was (20.8 +/- 0.8) vs
      (32.9 +/- 1.5), excellent in 6, good in 10, with no poor score, while the pre-
      and post-operation VAS score was (3.3 +/- 0.8) vs (0.6 +/- 0.5). CONCLUSION:
      Suture anchor fixation guided by arthroscopy is good for bankart injury caused by
      recurrent shoulder dislocation, which has many advantages, such as mini-invasion,
      rapid recovery and a satisfactory outcome in function and motion.

PMID- 23545825
TI  - [Meta analysis of efficacy and safety between mammotome minimally invasive
      operation and open excision for benign breast tumor].
AB  - OBJECTIVE: To compare the efficacy and safety between mammotome minimally
      invasive operation and conventional open excision for benign breast tumor.
      METHODS: A computer-based online search of Medline, PubMed, Embase, Ovid,
      Cochrane Library, VIP, Wanfang, CNKI and Chinese Biological Medicine Database was
      performed, and conference references were manually searched. With the Cochrane
      Collaboration Guidelines, all randomized controlled trials comparing mammotome
      minimally invasive operation and conventional open excision were systematically
      reviewed. The Cochrane Collaboration's RevMan 5.0 software was used for data
      analysis. RESULTS: A total of 15 studies involving 5256 patients was included.
      Meta-analyses showed no significant difference in the size of tumor,
      postoperative hematomas, ecchymosis, ecchymoma and residual disease between
      mammotome minimally invasive operation and conventional open excision. Mammotome
      minimally invasive operation was superior to open excision as to the size of
      incision, intraoperative blood loss, surgical duration, healing time, size of
      scar, wound infection and breast deformation. CONCLUSION: Mammotome minimally
      invasive surgery is an ideal method for benign breast tumor.

PMID- 23545824
TI  - [Meta analysis of acupuncture in the treatment of optic atrophy].
AB  - OBJECTIVE: To evaluate the efficacy and safety of acupuncture for optic atrophy.
      METHODS: All the randomized controlled trials (RCTs) on optic atrophy treatment
      with acupuncture were included after retrieving the PubMed, Embase, Cochrane
      Library, CBM, CNKI, VIP, Wanfang database from their establishment to November
      2012. The bibliographies of the included studies were retrieved as well. The
      quality of RCTs meeting the inclusion criteria was evaluated and the data were
      extracted. Meta-analyses were performed with Stata 11.2 software. RESULTS:
      Thirteen RCTs involving 1180 eyes were included. Meta-analyses showed that the
      effect of acupuncture or combined with medicine was superior to medicine alone in
      terms of total effectiveness [OR=3.281, 95% CI ( 2.517, 4.278)], visual acuity
      [3.287, 95% CI (2.193, 4.925)], and visual field [3.215, 95% CI (1.580, 6.543)].
      The visual sensitivity and P-VEP test showed the similar results. CONCLUSION:
      Acupuncture is superior to medicine in terms of improved visual acuity, visual
      field and P-VEP. However, large samples, and high-quality studies are needed for
      stronger evidence.

PMID- 23545826
TI  - [Weighted TOPSIS method and weighted RSR method in the construction of drug
      supervision and supply networks in rural areas of Hunan].
AB  - OBJECTIVE: To evaluate the rationality and validity of weighted TOPSIS method and
      weighted RSR method to evaluate drug supervision and supply networks construction
      in rural areas of Hunan . METHODS: Data of drug network construction in rural
      Hunan in 2010 were used to establish a comprehensive evaluation model, and
      weighted TOPSIS and RSR method were applied to this model and the results of
      which were compared to that of synthetical scored method to examine the validity.
      RESULTS: A comprehensive evaluation model was established, comprising of 3
      primary indices, 8 secondary indices and 56 tertiary ones. The result of weighted
      RSR method was highly correlated to that of synthetical scored method, yet the
      result of TOPSIS was less correlated to the formers. All correlations were
      significant (P<0.01). CONCLUSION: Both weighted RSR and TOPSIS are not perfect
      methods, but the application of the methods in drug network evaluation is
      scientific and effective.

PMID- 23545827
TI  - [Endothelial progenitor cells: the new target of anti-atherosclerosis drugs].
AB  - Endothelial progenitor cells (EPCs) are a kind of progenitor cells with high
      potential of proliferation, which exist in the bone marrow, umbilical cord blood,
      and peripheral blood. Under certain conditions, EPCs can differentiate into
      mature vascular endothelial cells. Many studies have shown that EPCs could delay
      the onset and development of atherosclerosis by promoting the repair of the
      endothelium and neovascularization. EPCs have also been considered to be a
      biological marker for cardiovascular diseases. Recent investigations demonstrate
      that EPCs can mediate the effect of some anti-atherosclerosis drugs. This paper
      reviews the role of EPCs in atherosclerosis and the influence of drugs on EPC
      function. The feasibility and the problem of using EPCs as a treatment strategy
      are also discussed.

PMID- 23545828
TI  - [Diagnosis and treatment of warfarin resistance].
AB  - Warfarin resistance is a phenomenon that patients need to take much higher than
      normally prescribed dosage of warfarin to maintain the target therapeutic
      international normalized ratio (INR) range, or even fail to reach the target INR.
      Warfarin resistance can be categorized in etiologic terms as hereditary vs
      acquired, or in pharmacologic terms as pharmacokinetic vs pharmacodynamic. Once
      warfarin resistance is diagnosed, the type of resistance should be determined as
      soon as possible so that treatment could be oriented toward the causes. Poor
      compliance, genetic mutations, concurrent medications that could decrease the
      absorption or increase the clearance of warfarin, and consumption of diet rich in
      vitamin K are the major reasons for warfarin resistance. Educating patients,
      increasing warfarin dosage and switching to other anticoagulants would be
      effective for warfarin resistance.

PMID- 23545829
TI  - [MicroRNA and metabolism regulation].
AB  - MicroRNAs have been identified as a new class of regulatory molecules that affect
      many biological functions by interferring the target gene expressions. Latest
      studies demonstrate that microRNAs can influence many pivotal bio-processes and
      deeply involve in the metabolism of glucose, lipid and amino acid and biological
      oxidation. For glucose metabolism, microRNAs are related to insulin secretion,
      insulin sensitivity, glucose uptake, glycolysis, oxidation and mitochondrial
      function. For lipid matebolism, microRNAs can regulate the target genes related
      to lipid biosynthesis, catabolism and transportation. MicroRNAs can influence
      glutamine catabolism.

PMID- 23545830
TI  - [MicroRNA in the regulation of nervous system development].
AB  - Several types of molecules, including the small non-coding RNAs, are involved in
      the precision regulation of neural development. The expression of microRNAs
      appears in a specific spatialtemporal sequence during the neural development, and
      abnormal expression may lead to neural dysplasia. MicroRNAs also play important
      roles in the regulation of cell biological behaviors in terms of survival,
      proliferation and differentiation. Neural stem cells are the mother cell of the
      nervous system. The proliferation, differentiation and migration of neural stem
      cells are tightly controlled so as to generate appropriate number and phenotype
      of daughter cells to ensure normal neural development. MicroRNAs are involved in
      the regulation of neural stem cell proliferation and differentiation via
      affecting the expression and function of their target mRNAs.

PMID- 23545831
TI  - [3-dimensional speckle tracking echocardiography for left ventricular rotation
      and twist in patients with hypertension].
AB  - OBJECTIVE: To analyze the characteristics of left ventricular rotation and twist
      in patients with essential hypertension (EH) of different left ventricular
      configurations by 3-dimensional speckle tracking echocardiography (3D-STE).
      METHODS: A total of 106 EH patients were divided into 4 groups: a left
      ventricular normal configuration (LVN) group (n=30), a concentric remodeling
      (CCR) group (n=31), a concentric hypertrophy (CCH) group (n=29), an eccentric
      hypertrophy (ECH) group (n=16), and a control group of 30 healthy subjects. The
      parameters of LVEF, peak basal rotation (Prot-B), peak apical rotation (Prot-A),
      left ventricular peak apical rotation (LV-rot), and left ventricular peak apical
      twist (LV-tw) were compared. RESULTS: The left ventricular mass index in the EH
      groups, which kept increasing, was higher than that in the normal control group
      (P<0.05). Compared with the normal control group, LVN and ECH group, the left
      ventricular posterior wall thickness, interventricular septum at end-diastole,
      and relative wall thickness significantly increased in the CCH and CCR group
      (P<0.05). LVEF showed no significant difference among the normal control, LVN,
      CCR and CCH group (P>0.05), but LVEF was lower in the ECH group than in other
      groups (P<0.05). Compared with the normal control group, Prot-B, Prot-A, LVrot
      and LVtw were significantly higher in the LVN, CCR and CCH group (P<0.05), but
      decreased in the ECH group (P<0.05). CONCLUSION: 3D-STE can evaluate the left
      ventricular rotation and twist in EH patients with different configurations, and
      reflect changes in the left ventricular systolic function in EH of different
      configurations.

PMID- 23545832
TI  - [Visfatin level after laparoscopic Roux-en-Y gastric bypass surgery in patients
      with Type 2 diabetes].
AB  - OBJECTIVE: To investigate the change in serum visfatin level after laparoscopic
      Roux-en-Y gastric bypass surgery in patients with Type 2 diabetes mellitus (T2DM)
      and to explore the relationship between visfatin insulin resistance and diabetes.
      METHODS: Thirty-three patients with Type 2 diabetes were studied before and after
      the gastric bypass surgery. The level of fasting serum visfatin was measured by
      enzyme-linked immunosorbent assay. Fasting plasma glucose (FPG), glycated
      hemoglobin (HbA1c) and fasting insulin (FINS) were measured before and after the
      gastric bypass surgery. RESULTS: Compared with before the operation, the
      indicators of HbA1c, FINS, and insulin resistance index (HOMA-IR) were decreased
      after the laparoscopic Roux-en-Y gastric bypass surgery. The body mass index
      (BMI) [(24.53 +/- 0.62) kg/m2 vs (26.71 +/- 0.69) kg/m2] was decreased, with
      significant difference (P<0.001). The serum visfatin level [(9.79 +/- 0.64)
      ng/mL] was significantly lower than before the operation [(38.24 +/- 5.32)
      ng/mL], with significant difference (P<0.001). CONCLUSION: Serum level of
      visfatin is decreased in T2DM patients who undergo gastric bypass surgry,
      reflecting an improvement in insulin resistance and diabetes.

PMID- 23545833
TI  - [Ventricular septal plication for post infarction anterior and anterior-septal
      aneurysm of the left ventricle].
AB  - OBJECTIVE: To determine the use of septal plication with Dor or Cooley procedure
      for post infarction anterior and anterior-septal aneurysm of the left ventricle.
      METHODS: A total of 23 patients with post infarction anterior and anterior-septal
      aneurysm of the left ventricle underwent septal plication and Dor or Cooley
      procedure along with coronary artery bypass grafting concomitantly. Data of NYHA
      grading, left ventricular end diastolic volume index (LVEDVI), left ventricular
      end systolic volume index (LVESVI) and left ventricular ejection fraction (LVEF)
      were recorded before the surgery, before discharge and 3 months after the
      surgery. RESULTS: Compared with the preoperative data, the NYHA grading before
      the discharge and 3 months after the surgery improved from 3.21 +/- 0.62 to 1.72
      +/- 0.31 and 1.57 +/- 0.23(P<0.05); LVEDVI decreased from (102.31 +/- 18.71)
      mL/m2 to (62.11 +/- 6.21) mL/m2 and (54.63 +/- 4.54) mL/m2 (P<0.05); LVESVI
      decreased from (69.32 +/- 17.48) mL/m2 to (30.23 +/- 3.25)mL/m2 and (28.34 +/-
      3.12) mL/m2; while LVEF increased from (32.92 +/- 8.12)% to (48.78 +/- 4.51)% and
      (50.52 +/- 4.68)% (P<0.05), respectively. CONCLUSION: Ventricular septal
      plication combined with Dor or Cooley procedure can remarkably improve the left
      heart function in patients with post infarction ventricular aneurysm.

PMID- 23545834
TI  - Initiation of ovarian stimulation independent of the menstrual cycle: a case
      control study.
AB  - PURPOSE: In the GnRH-antagonist protocol, ovarian stimulation with gonadotropins
      typically commences on cycle day 2 or 3. Initiation of ovarian stimulation with a
      spontaneously occurring menstruation, however, poses significant organizational
      challenges for treatment centres and patients alike. It has previously been
      demonstrated in the context of fertility preservation that initiation of
      stimulation in the luteal phase is feasible in terms of retrieval of mature
      oocytes for cryopreservation. Herein, we report the extension of this concept to
      a routine IVF setting with the aim of establishing an ovarian stimulation
      protocol, which can be utilized independent of menstruation. Because of
      asynchrony of endometrium and embryo in such a setting, all fertilized oocytes
      have to be cryopreserved for a later transfer. METHODS: This was a prospective,
      case-control study (trial registration: NCT00795041) on the feasibility of
      starting ovarian stimulation in a GnRH-antagonist protocol in the luteal phase.
      Inclusion criteria were: IVF or ICSI; 18-36 years; <=3 previous IVF/ICSI
      attempts; BMI 20-30 kg/m(2); regular cycle (28-35 days); luteal phase
      progesterone >7 ng/ml at initiation of stimulation. Exclusion criteria were:
      PCOS, endometriosis >=AFS III degrees , unilateral ovary, expected poor response.
      Stimulation was performed with highly purified uFSH (Bravelle(r)) 300 IU/day and
      0.25 mg/day GnRH-antagonist starting on cycle day 19-21 of a spontaneous
      menstrual cycle and commencing until hCG administration when three follicles >=17
      mm were present. All 2PN stage oocytes were vitrified for later transfers in
      programmed cycles. Feasibility was defined as the achievement of ongoing
      pregnancies progressing beyond the 12th gestational week in at least 2/10 study
      subjects (primary outcome). Secondary outcomes were gonadotropin consumption per
      oocyte obtained, stimulation duration, and fertilization rates. Study subjects
      were matched in a 1:3 ratio with concomitantly treated control cases of similar
      age, BMI, and duration of infertility who were treated in a conventional GnRH
      antagonist protocol with 150-225 rFSH or HP-HMG/day. RESULTS: The study group
      consisted of ten subjects, mean age 31.4 years, BMI 25.4 kg/m(2), of which one
      had fertilization failure. Mean stimulation duration was 11.7 (SD 1.6) vs. 9.1
      (SD 1.3) days, mean cumulative FSH dose was 3,495.0 (SD 447.5) vs. 2,040.5 (SD
      576.2) IU, and mean number of oocytes was 8.8 (SD 5.0) vs. 10.0 (SD 5.4) in study
      vs. control group, respectively. Per follicle >=10 mm, the cumulative FSH dose
      was 274.5 (SD 130.8) IU vs. 245.2 (SD 232.3) IU in study and control groups,
      respectively. Cumulative ongoing pregnancy rates were 1/10 (10 %) and 6/30 (20.0
      %) in study and control group, respectively (difference: 10 %, 95 % confidence
      interval of the difference: -29.2-22.2 %, p = 0.47). Fertilization rate was
      similar between groups, with 63.5 % (SD 32.9) in the study and 61.3 % (SD 26.7)
      in the control group, respectively. Serum estradiol levels were significantly
      lower on the day of triggering final oocyte maturation with 1,005.3 (SD 336.2)
      vs. 1,977.4 pg/ml (SD 1,106.5) in study and control group, respectively.
      Similarly, peak estradiol biosynthesis per growing follicle >=10 mm was lower in
      the study group (134 pg/ml, SD 158.4 vs. 186.7 pg/ml, SD 84.7). CONCLUSIONS: Per
      retrieved oocyte, a nearly threefold higher dose of FSH had to be administered
      when ovarian stimulation had been initiated in the luteal phase. Furthermore, the
      present study casts doubt on the efficacy of initiating ovarian stimulation in
      the luteal phase in terms of pregnancy achievement. Thus, this concept is
      currently not feasible for routine use, and it should also be explored further
      before using it at larger scale in the context of emergency stimulation for
      fertility preservation.

PMID- 23545835
TI  - Author's reply: To PMID 23296465.

PMID- 23545836
TI  - Combination of non-invasive and semi-invasive tests for diagnosis of minimal to
      mild endometriosis.
AB  - OBJECTIVES: Non-surgical diagnostic approach for endometriosis would be of great
      gain to both physicians and patients. The aim of this study was to evaluate the
      diagnostic value of serum measurement of IL-6 combined with the presence of nerve
      fibres in the functional layer of endometrium for diagnosis of minimal-mild
      endometriosis. METHODS: In this prospective study 114 women who underwent
      laparoscopy for infertility and/or pelvic pain were divided into two groups:
      control cases (40 cases) with no pathologic findings; and endometriosis patients
      (74 cases) [subdivided into stages 1-2 or minimal-mild (MM) and stages 3-4 or
      moderate-severe cases]. Blood was drawn one day before laparoscopy and stored for
      subsequent analysis of IL-6. Endometrial biopsy was obtained prior to laparoscopy
      and Immunohistochemistry was performed using the pan-neuronal marker protein gene
      product 9.5(PGP9.5). Then laparoscopic diagnosis of endometriosis confirmed by
      histopathology was done. RESULTS: Serum IL-6 with a threshold of 15.4 pg/ml was
      found to be able to diagnose MM endometriosis with 89.5 % sensitivity and 82.5 %
      specificity, but sensitivity and specificity of presence of nerve fibres in the
      functional layer of endometrium were 92 % and 80 % respectively. When two
      diagnostic modalities were combined the sensitivity and specificity were raised
      to 100 and 92.5 % respectively. CONCLUSIONS: Combination of both serum IL-6 and
      presence of nerve fibres in the endometrium is more reliable method for diagnosis
      of MM endometriosis than in single test.

PMID- 23545837
TI  - Modular generation of fluorescent phycobiliproteins.
AB  - Phycobiliproteins are brightly-fluorescent light-harvesting pigments for
      photosynthesis in cyanobacteria and red algae. They are also of interest as
      fluorescent biomarkers, but their heterologous generation in vivo has previously
      required multiple transformations. We report here a modular approach that
      requires only two DNA segments. The first codes for the apo-protein. The second
      codes for fusions capable of chromophore biosynthesis and its covalent attachment
      to the apo-protein; it contains the genes of heme oxygenase, a bilin reductase,
      and a chromophore lyase. Phycobiliproteins containing phycoerythrobilin
      (lambda(fluor) ~ 560 nm), phycourobilin (lambda(fluor) ~ 500 nm), phycocyanobilin
      (lambda(fluor) ~ 630 nm) or phycoviolobilin (lambda(fluor) ~ 580 nm) were
      obtained in high yield in E. coli. This approach facilitates chromophorylation
      studies of phycobiliproteins, as well as their use for fluorescence labeling
      based on their high fluorescence.

PMID- 23545838
TI  - Highly propylene-selective supported zeolite-imidazolate framework (ZIF-8)
      membranes synthesized by rapid microwave-assisted seeding and secondary growth.
AB  - Here we report a rapid and simple microwave-assisted seeding technique for the
      synthesis of high-quality ZIF-8 membranes with an average propylene-propane
      selectivity of about 40. The new seeding method was found to be applicable to
      other ZIFs including ZIF-7 and SIM-1.

PMID- 23545839
TI  - Effect of the ACGME 16-hour rule on efficiency and quality of care: duty hours
      2.0.

PMID- 23545841
TI  - Loneliness at the bench. Is the PhD experience as emotionally taxing as it is
      mentally challenging?

PMID- 23545842
TI  - Nanoscale analysis of the morphology and surface stability of calcium carbonate
      polymorphs.
AB  - Under earth surface conditions, in ocean and natural water, calcium carbonate is
      ubiquitous, forming anhydrous and hydrous minerals. These hydrous phases are of
      considerable interest for their role as precursors to stable carbonate minerals.
      Atomistic simulation techniques have been employed here to perform a
      comprehensive and quantitative study of the structural and energetic stability of
      dry and hydrous surfaces of calcium carbonate polymorphs using two recently
      developed forcefields. Results show that the dry forms are prone to ductility;
      while hydrous phases are found to be brittle. The (001) surface of
      monohydrocalcite appears to be the most stable (0.99 J/m(2)) whereas for the
      ikaite phase, the (001) surface is the most stable. The corresponding value is
      0.2 J/m(2), i.e. even lower than the surface energy of the Beautiful computed
      morphology pictures are obtained with Xiao's model and are very similar to the
      observed SEM images.

PMID- 23545843
TI  - Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)
      induced oxidative stress in HIT-T15 pancreatic beta cells.
AB  - Reactive oxygen species (ROS)-induced pancreatic beta cell death affects insulin
      secretion and is important in the pathogenesis of diabetes. Lagerstroemia
      speciosa, a traditional folk medicine, has been used for t he prevention and
      treatment of diabetes. However, whether Lagerstroemia speciosa has a
      cytoprotective effect on pancreatic beta cells remains to be elucidated. The
      present study aimed to investigate the cytoprotective effects of hot water
      extracts from Lagerstroemia speciosa leaves (LWE) on 3-morpholinosydnonimine (SIN
      1)-induced oxidative damage in Syrian hamster pancreatic insulinoma HIT-T15
      cells. The HIT-T15 cells were first treated with SIN-1 (50 uM) for 24 h and then
      co-incubated with LWE for 48 h. SIN-1 significantly decreased HIT-T15 cell
      viability (P<0.05); however, LWE did not exert a significant cytotoxic effect and
      increased the viability of HIT-T15 cells in a dose-dependent manner. To further
      investigate the protective effects of LWE on SIN-1-induced oxidative stress in
      HIT-T15 cells, the cellular levels of ROS, lipid peroxidation and endogenous
      antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GSH-px), were determined. LWE decreased the intracellular
      levels of ROS and lipid peroxidation, and increased the activities of antioxidant
      enzymes. These results suggest that LWE has a cytoprotective effect against SIN-1
      induced oxidative stress in HIT-T15 cells through the inhibition of lipid
      peroxidation, a decrease in ROS levels and an increase in antioxidant enzyme
      activity. In addition, LWE increased insulin secretion in SIN-1-treated HIT-T15
      cells. Our results suggested that LWE were effective in the treatment of
      diabetes. Further studies are required to study the anti-diabetic molecular
      mechanism in a cell model.

PMID- 23545844
TI  - Smart wormlike micelles.
AB  - A major scientific challenge of the past decade pertaining to the field of soft
      matter has been to craft 'adaptable' materials, inspired by nature, which can
      dynamically alter their structure and functionality on demand, in response to
      triggers produced by environmental changes. Amongst these, 'smart' surfactant
      wormlike micelles, responsive to external stimuli, are a particularly recent area
      of development, yet highly promising, given the versatility of the materials but
      simplicity of the design-relying on small amphiphilic molecules and their
      spontaneous self-assembly. The switching 'on' and 'off' of the micellar assembly
      structures has been reported using electrical, optical, thermal or pH triggers
      and is now envisaged for multiple stimuli. The structural changes, in turn, can
      induce major variations in the macroscopic characteristics, affecting properties
      such as viscosity and elasticity and sometimes even leading to a spontaneous and
      effective 'sol-gel' transition. These original smart materials based on wormlike
      micelles have been successfully used in the oil industry, and offer a significant
      potential in a wide range of other technological applications, including
      biomedicine, cleaning processes, drag reduction, template synthesis, to name but
      a few. This review will report results in this field published over the last few
      years, describe the potential and practical applications of stimuli-responsive
      wormlike micelles and point out future challenges. 

PMID- 23545845
TI  - Novel stable (3E,7E)-3,7-bis(2-oxoindolin-3-ylidene)benzo[1,2-b:4,5-b']difuran
      2,6(3H,7H)-dione based donor-acceptor polymer semiconductors for n-type organic
      thin film transistors.
AB  - (3E,7E)-3,7-Bis(2-oxoindolin-3-ylidene)benzo[1,2-b:4,5-b']difuran-2,6(3H,7H)
      dione (IBDF) was used as a new electron-acceptor building block for polymer
      semiconductors with very low-lying energy levels. A copolymer of IBDF and
      thiophene showed stable electron transport performance in thin film transistors.

PMID- 23545846
TI  - Determination of the mutagenic and genotoxic potential of simulated leachate from
      an automobile workshop soil on eukaryotic system.
AB  - Contamination of soil and water bodies with spent engine oil and petroleum
      products is a serious ecological problem, primarily in the automobile workshops
      and garages. This has potential short and chronic adverse health risks.
      Information is currently scarce on the potential mutagenicity and genotoxicity of
      such wastes. In this study, the potential mutagenic and genotoxic effects of
      simulated leachate from automobile workshop soil in Sagamu, Ogun state, Nigeria,
      were investigated. The assays utilized were bone marrow micronucleus (MN) and
      chromosome aberration (CA), sperm morphology and sperm count in mice. The
      physicochemical analysis of the leachate was also carried out. Experiments were
      carried out at concentrations of 1, 5, 10, 25, 50, 75 and 100% (volume per
      volume; leachate:distilled water) of the leachate sample. MN analysis showed a
      concentration-dependent induction of micronucleated polychromatic erythrocytes
      across the treatment groups. In the CA test, there was concentration-dependent
      significant reduction in mitotic index and induction of different types of CAs.
      Assessment of sperm shape showed a significant increase in sperm abnormalities
      with significant decrease in mean sperm count in treated groups. Heavy metals
      analyzed in the tested sample are believed to contribute significantly to the
      observed genetic damage. This indicates that automobile workshop soil-simulated
      leachate contains potential genotoxic agents and constitutes a genetic risk in
      exposed human population. 

PMID- 23545847
TI  - Smoking cessation care in state-operated or state-supported psychiatric
      hospitals: from policy to practice.
AB  - OBJECTIVES: The aims of this study were to identify changes in smoking policies
      and their implementation and to determine the level of smoking cessation care
      provided at state-operated or state-supported psychiatric inpatient hospitals.
      METHODS: Hospitals were surveyed in 2008 (N=219) and 2011 (N=206) about their
      smoking policies and practices, and changes in specific policies and practices,
      such as staff specialty training about smoking cessation care, assessment at
      intake, provision of smoking cessation treatment and education, and aftercare
      planning, were examined. Smoking cessation care was categorized as best, good,
      average, or poor. RESULTS: The survey was completed in both 2008 and 2011 by 108
      hospitals. The number of hospitals prohibiting smoking rose by 73%, from 48% in
      2008 to 83% in 2011. The provision of specialty training to staff did not
      significantly improve. Nearly all hospitals assessed smoking status at admission,
      and nicotine replacement therapy was provided by more hospitals than any other
      treatment in both 2008 and 2011. The number of hospitals providing no follow-up
      of smoking cessation care after discharge dropped significantly, from 64% to 41%,
      and significantly more provided good versus average smoking cessation care.
      CONCLUSIONS: Analysis of smoking policies at state-operated or state-supported
      psychiatric inpatient hospitals found significant movement in adopting nonsmoking
      policies and some increase in active treatment, notably wellness counseling.
      Educational resources have not reached full penetration, and continuum of care
      activities are also lagging behind. Additional resources and staff training may
      be needed to continue to address smoking cessation both during and after
      hospitalization.

PMID- 23545848
TI  - Prognostic value of changes in the expression of stem cell markers in the
      peripheral blood of patients with colon cancer.
AB  - Cancer stem cells play an important role in carcinogenesis and resistance to
      treatment and may lead to metastasis. The isolation of circulating stem cells
      involves cell sorting based on the presence of cell surface markers. Many surface
      markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the
      present study, we determined the expression of different stem cell markers and
      their variation in expression at different stages of the treatment process.
      Samples of EDTA blood were collected from metastatic colorectal cancer patients,
      and circulating cancer stem cells were isolated for the analysis of the
      expression of stem cell markers using RT-PCR. These findings were correlated with
      the response to therapy. All statistical analyses were performed using the
      GraphPad Prism 5.03 software. Significant differences were found in the
      expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences
      were found in c-Kit expression. Correlation in the expression levels of most of
      the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a
      predictive value for colon cancer behavior. Evaluation of this stem cell gene
      expression panel may be useful for predicting the response during the process of
      treatment, and the relative easy access to samples facilitates this method.
      Moreover the correlation between CD133 and TWIST1 expression may be associated
      with tumor regrowth and metastatic relapse.

PMID- 23545849
TI  - Chemical welding of binary nanoparticles: room temperature sintering of CuSe and
      In2S3 nanoparticles for solution-processed CuInS(x)Se(1-x) solar cells.
AB  - Chemical welding of oppositely charged dissimilar metal chalcogenide
      nanomaterials is reported to produce a quaternary metal chalcogenide. CuSe and
      In2S3 nanoparticles were synthesized with opposite surface charges by stabilizing
      with polyacrylic acid and polydiallyldimethylammonium chloride. Upon mixing these
      nanoparticles at room temperature, the electrostatic attraction induced
      coalescence of these nanoparticles and led to the formation of CuInSxSe1-x
      nanoparticles.

PMID- 23545852
TI  - Optical micromanipulation of active cells with minimal perturbations: direct and
      indirect pushing.
AB  - The challenge to wide application of optical tweezers in biological
      micromanipulation is the photodamage caused by high-intensity laser exposure to
      the manipulated living systems. While direct exposure to infrared lasers is less
      likely to kill cells, it can affect cell behavior and signaling. Pushing cells
      with optically trapped objects has been introduced as a less invasive
      alternative, but the technique includes some exposure of the biological object to
      parts of the optical tweezer beam. To keep the cells farther away from the laser,
      we introduce an indirect pushing-based technique for noninvasive manipulation of
      sensitive cells. We compare how cells respond to three manipulation approaches:
      direct manipulation, pushing, and indirect pushing. We find that indirect
      manipulation techniques lessen the impact of manipulation on cell behavior. Cell
      survival increases, as does the ability of cells to maintain shape and wiggle.
      Our experiments also demonstrate that indirect pushing allows cell-cell contacts
      to be formed in a controllable way, while retaining the ability of cells to
      change shape and move.

PMID- 23545853
TI  - Spatiotemporal quantification of cell dynamics in the lung following influenza
      virus infection.
AB  - Lung injury caused by influenza virus infection is widespread. Understanding lung
      damage and repair progression post infection requires quantitative spatiotemporal
      information on various cell types mapping into the tissue structure. Based on
      high content images acquired from an automatic slide scanner, we have developed
      algorithms to quantify cell infiltration in the lung, loss and recovery of Clara
      cells in the damaged bronchioles and alveolar type II cells (AT2s) in the damaged
      alveolar areas, and induction of pro-surfactant protein C (pro-SPC)-expressing
      bronchiolar epithelial cells (SBECs). These quantitative analyses reveal:
      prolonged immune cell infiltration into the lung that persisted long after the
      influenza virus was cleared and paralleled with Clara cell recovery; more rapid
      loss and recovery of Clara cells as compared to AT2s; and two stages of SBECs
      from Scgb1a1+ to Scgb1a1-. These results provide evidence supporting a new
      mechanism of alveolar repair where Clara cells give rise to AT2s through the SBEC
      intermediates and shed light on the understanding of the lung damage and repair
      process. The approach and algorithms in quantifying cell-level changes in the
      tissue context (cell-based tissue informatics) to gain mechanistic insights into
      the damage and repair process can be expanded and adapted in studying other
      disease models.

PMID- 23545854
TI  - Toward improving fine needle aspiration cytology by applying Raman
      microspectroscopy.
AB  - ABSTRACT. Medical diagnosis of biopsies performed by fine needle aspiration has
      to be very reliable. Therefore, pathologists/cytologists need additional
      biochemical information on single cancer cells for an accurate diagnosis.
      Accordingly, we applied three different classification models for discriminating
      various features of six breast cancer cell lines by analyzing Raman
      microspectroscopic data. The statistical evaluations are implemented by linear
      discriminant analysis (LDA) and support vector machines (SVM). For the first
      model, a total of 61,580 Raman spectra from 110 single cells are discriminated at
      the cell-line level with an accuracy of 99.52% using an SVM. The LDA
      classification based on Raman data achieved an accuracy of 94.04% by
      discriminating cell lines by their origin (solid tumor versus pleural effusion).
      In the third model, Raman cell spectra are classified by their cancer subtypes.
      LDA results show an accuracy of 97.45% and specificities of 97.78%, 99.11%, and
      98.97% for the subtypes basal-like, HER2+/ER-, and luminal, respectively. These
      subtypes are confirmed by gene expression patterns, which are important
      prognostic features in diagnosis. This work shows the applicability of Raman
      spectroscopy and statistical data handling in analyzing cancer-relevant
      biochemical information for advanced medical diagnosis on the single-cell level.

PMID- 23545855
TI  - Imetelstat (a telomerase antagonist) exerts off-target effects on the
      cytoskeleton.
AB  - Telomerase is a cellular ribonucleoprotein reverse transcriptase that plays a
      crucial role in telomere maintenance. This enzyme is expressed in approximately
      90% of human tumors, but not in the majority of normal somatic cells. imetelstat
      sodium (GRN163L), is a 13-mer oligonucleotide N3'->P5' thio-phosphoramidate lipid
      conjugate, which represents the latest generation of telomerase inhibitors
      targeting the template region of the human functional telomerase RNA (hTR)
      subunit. In preclinical trials, this compound has been found to inhibit
      telomerase activity in multiple cancer cell lines, as well as in vivo xenograft
      mouse models. Currently, GRN163L is being investigated in several clinical
      trials, including a phase II human non-small cell lung cancer clinical trial, in
      a maintenance setting following standard doublet chemotherapy. In addition to the
      inhibition of telomerase activity in cancer cell lines, GRN163L causes
      morphological cell rounding changes, independent of hTR expression or telomere
      length. This leads to the loss of cell adhesion properties; however, the
      mechanism underlying this effect is not yet fully understood. In the present
      study, we observed that GRN163L treatment leads to the loss of adhesion in A549
      lung cancer cells, due to decreased E-cadherin expression, leading to the
      disruption of the cytoskeleton through the alteration of actin, tubulin and
      intermediate filament organization. Consequently, the less adherent cancer cells
      initially cease to proliferate and are arrested in the G1 phase of the cell
      cycle, accompanied by decreased matrix metalloproteinase-2 (MMP-2) expression.
      These effects of GRN163L are independent of its telomerase catalytic activity and
      may increase the therapeutic efficacy of GRN163L by decreasing the adhesion,
      proliferation and metastatic potential of cancer cells in vivo.

PMID- 23545857
TI  - Evaluation of differential protein expression in Haliclona aquarius and sponge
      associated microorganisms under cadmium stress.
AB  - A comparative proteomic approach was used to assess differentially expressed
      proteins in marine sponges after 36 h of exposure to cadmium (Cd). After
      separation performed by 2-D polyacrylamide gel electrophoresis, 46 protein spots
      indicated differential expression, and 17 of these proteins were identified by
      electrospray ionization quadrupole time-of-flight mass spectrometry. From the
      proteins identified, 76% were attributed to sponge-associated microorganisms
      (fungi and bacteria), and 24% were attributed to Haliclona aquarius. Some of the
      proteins that were identified may be related to cell proliferation and
      differentiation or processes of oxidative stress repair and energy procurement.
      An integrated evaluation based on spot expression levels and the postulated
      functions of these proteins allowed a more accurate evaluation of the stress
      caused to the sponge holobiont system by cadmium exposure. This study could
      provide new insights into the use of a proteomic approach in the marine sponge to
      assess the effects of Cd pollution in a marine environment.

PMID- 23545858
TI  - Can Edman degradation be used for quantification? Isotope-dilution liquid
      chromatography-electrospray ionization tandem mass spectrometry and the long-term
      stability of 20 phenylthiohydantoin-amino acids.
AB  - Edman degradation is a well-known method for obtaining amino acid (AA) sequences
      from a peptide by means of sequential reactions that release the N-terminal AAs
      from the peptide as a phenylthiohydantoin (PTH) derivative. Because of unexpected
      loss during the reaction and handling, there are few reports of use of this
      reaction for quantification. This manuscript describes the development of isotope
      dilution liquid chromatography-electrospray ionization tandem mass spectrometry
      for 20 PTH-AA derivatives, and long-term stability testing of PTH-AAs to ensure
      quantitative quality in the reaction. The 20 corresponding [(13)C6]-PTH-AAs were
      prepared by use of a one-pot reaction involving a mixture of [(13)C6]-Edman
      reagent and 20 AAs. Good linearity was observed for standard curves for the PTH
      AAs, using the corresponding [(13)C6]-PTH-AAs as internal standards (1-100 pmol
      per injection, r(2) = 0.989-1.000). Serum albumin (human), pepsin (porcine
      stomach mucosa), alpha-casein (bovine milk), ribonuclease A (bovine), lysozyme
      (chicken egg white), and insulin (bovine) subjected to Edman degradation were
      examined as model proteins and peptides for N-terminal AA analysis. The results
      of the impurity test were satisfactory. Yield from the entire reaction with human
      serum albumin was estimated to be at least 75%, indicating great potential for
      absolute quantification of proteins without protein standards.

PMID- 23545859
TI  - Quantitative trace analysis of fullerenes in river sediment from Spain and soils
      from Saudi Arabia.
AB  - A quantitative method based on ultrasound-assisted toluene extraction followed by
      liquid chromatography-electrospray ionization-tandem mass spectrometry for the
      analysis of C60 and C70 fullerenes, N-methylfulleropyrrolidine, [6, 6]-phenyl C61
      butyric acid methyl ester and [6, 6]-thienyl C61 butyric acid methyl ester has
      been developed. The method was validated using fortified blank river sediments
      according to the criteria of Commission Decision 2002/657/EC. The method limits
      of detection ranged from 14 to 290 pg/g, making it suitable for its application
      in environmental analysis. The method has been applied to investigate fullerene
      content in 58 soil samples collected from different urban and industrial areas in
      Saudi Arabia and in river sediment from six different sites in the Llobregat
      River Basin. In addition, in the case of the Llobregat River, superficial water
      samples from the same sites of the sediments were collected and analysed using a
      previous method. In soils from Saudi Arabia, C60-fullerene was the only compound
      that was detected and quantified in 19% of samples. In the sediments of the
      Llobregat River, C60-fullerene was also the only one detected (33% of the
      samples), while in river water, C70-fullerene was the most frequent compound, and
      it was quantified in 67% of the samples. However, C60-fullerene was present in
      two of the six samples, but at higher concentrations than C70-fullerene, ranging
      from 0.9 to 7.8 ng/L.

PMID- 23545860
TI  - Three different brain tumours evolving from a common origin.
AB  - Despite an improved understanding of the molecular aberrations that occur in
      glioblastoma, the use of molecularly targeted therapies have so far been
      disappointing. We present a patient with three different brain tumours:
      astrocytoma, glioblastoma and gliosarcoma. Genetic analysis showed that the three
      different brain tumours were derived from a common origin but had each developed
      unique genetic aberrations. Included in these, the glioblastoma had PDGFRA
      amplification, whereas the gliosarcoma had MYC amplification. We propose that
      genetic heterogeneity contributes to treatment failure and requires comprehensive
      assessment in the era of personalised medicine.

PMID- 23545861
TI  - Acute aortic dissection: pitfalls in the diagnosis.

PMID- 23545862
TI  - Incidence and implications of coronary artery disease in patients undergoing
      valvular heart surgery: the Indian scenario.
AB  - AIMS AND OBJECTIVES: We evaluated the incidence and implications of coronary
      artery disease (CAD) in patients above 40 years presenting for valve surgery.
      MATERIALS AND METHODS: Between January 2009 and December 2010, coronary
      angiography (CAG) was performed in all such patients ( n = 140). RESULTS:
      Coronaries were normal in 119 (Group I), and diseased in 21 (Group II). In Group
      II, 11 patients were < 50 years, 3 were between 51 and 60 years and 7 were > 61
      years. In 8 of these, only valve replacement was performed. Coronary artery
      bypass grafting (CABG) and aortic valve replacement was performed in 10, CABG and
      mitral valve replacement in 2 and CABG with mitral and aortic valve replacement
      in one. The number of vessels grafted in these 13 patients was 1.54 +/- 0.66.
      Hypertension and diabetes were significant ( P < 0.05) in this group. The
      mortality was significant in Group II (11 vs. 6, P < 0.05). Six patients died in
      Group II, 5 had severe aortic stenosis and severe left ventricular hypertrophy;
      the sixth patient had severe mitral stenosis and was in CHF. The predominant
      cause of death was congestive heart failure (CHF). CONCLUSIONS: Fifteen
      percentage of these patients had CAD. CAG should be performed routinely in these
      patients while presenting for valve surgery. Combined CABG and valve replacement
      carries high mortality (28.5%), especially in patients with aortic stenosis. The
      study suggests that the cardio-protective measures should be applied more
      rigorously in this subset of patients.

PMID- 23545863
TI  - Effect of levosimendan on hemodynamic changes in patients undergoing off-pump
      coronary artery bypass grafting: a randomized controlled study.
AB  - AIMS AND OBJECTIVE: We tested the hypothesis that use of levosimendan would be
      associated with better perioperative hemodynamics and cardiac function during off
      pump coronary artery bypass grafting (OPCAB) in patients with good left
      ventricular function. MATERIALS AND METHODS: Thirty patients scheduled for OPCAB
      were randomized in a double-blind manner to receive either levosimendan 0.1
      MUg/kg/min or placebo after induction of general anesthesia. The hemodynamic
      variables were measured after induction of anesthesia, at 6 minute after
      application of tissue stabilizer for the anastomoses of left anterior descending
      artery, diagonal artery, left circumflex artery, and right coronary artery and at
      6, 12, 18, and 24 hours after completion of surgery. RESULTS: Compared with
      placebo group, cardiac index (CI) was significantly higher and systemic vascular
      resistance index (SVRI) was significantly lower at 6, 12, 18, and 24 hour after
      surgery in levosimendan group. Norepinephrine was infused in 60% of the patients
      in the levosimendan group compared to 6.7% in the control group ( P < 0.05).
      Lactate and mixed venous oxygen saturation were not significantly different
      between groups. CONCLUSIONS: Levosimendan significantly increased CI and
      decreased SVRI after OPCAB but it did not show any outcome benefit in terms of
      duration of ventilation and intensive care unit stay.

PMID- 23545864
TI  - Impact of monitoring cerebral oxygen saturation on the outcome of patients
      undergoing open heart surgery.
AB  - AIMS AND OBJECTIVES: We studied the usefulness of regional cerebral oxygen
      saturation (rSO 2 ) monitoring during cardiopulmonary bypass (CPB) and evaluated
      effects of cerebral oxygen desaturation on the postoperative neurological
      outcome. MATERIALS AND METHODS: 100 patients were randomly allocated to either
      control or intervention group. In the control group rSO 2 was recorded
      continuously, but the attending anesthesiologist was blinded. In the intervention
      group specific interventions were initiated in case of cerebral desaturation.
      Neurocognitive testing was done using a simplified antisaccadic eye movement test
      (ASEM) and mini-mental state examination (MMSE). Data was analyzed using Chi
      square test, and unpaired t-test. RESULTS: In both the groups rSO 2 declined
      during CPB. The decrease in rSO 2 was significant ( P < 0.001) in the control
      group compared to the intervention group. In the intervention group the rSO 2
      mainly responded to an increase in mean arterial pressure. The area under the
      curve below threshold rSO 2 was significantly more ( P < 0.0001) in the control
      group compared to intervention group and a significant decrease in the MMSE and
      ASEM scores occurred in control group at one week and three months
      postoperatively. CONCLUSIONS: Monitoring of rSO 2 during CPB can significantly
      decrease the incidence of postoperative neurocognitive decline.

PMID- 23545865
TI  - The efficacy of caudal dexmedetomidine on stress response and postoperative pain
      in pediatric cardiac surgery.
AB  - AIMS AND OBJECTIVES: We studied efficacy of caudal dexmedetomidine (DEX) on
      attenuation of perioperative stress response and postoperative pain in pediatric
      patients undergoing cardiac surgery. MATERIALS AND METHODS: Forty patients, (ASA
      II, III), 1-3-years old were randomly allocated into two groups; group BD
      received caudal bupivacaine 0.25%, 2.5 mg/kg and DEX 0.5 MUg/kg and group BF
      received bupivacaine 2.5 mg/kg and fentanyl 1 MUg/kg. RESULTS: Serum cortisol and
      blood glucose levels increased in both groups but increases were significantly
      less in group BD. Poststernotomy cortisol level (ug/dl) was 55.3 +/- 5.1 vs. 90.4
      +/- 6.5; after cardio-pulmonary bypass (CPB) 84.1 +/- 6.2 vs. 153.1 +/- 8.5;
      after operation 78.3 +/- 8.1 vs. 150.2 +/- 9.8. Poststernotomy blood glucose
      level (mg/dl) was 93.6 +/- 7.2 vs. 125.6 +/- 5.5; after CPB 115.3 +/- 3.7 vs.
      175.3 +/- 10.4; and after operation 97.3 2 +/- 3 vs. 162.2 +/- 12. Heart rate and
      mean arterial pressure decreased significantly after caudal block in group BD
      relative to the baseline and compared with group BF ( P < 0.05). Group BD had
      lower pain scores at first hour 2 +/- 0.7 vs. 3 +/- 1.1 ( P = 0.04); second hour
      1.9 +/- 0.5 vs. 3.7 +/- 0.8, ( P = 0.008); fourth hour 2.4 +/- 0.8 vs. 4.3 +/-
      0.5 ( P = 0.03); and eighth hour 2.5 +/- 0.5 vs. 4.2 +/- 1.1 ( P = 0.03).
      CONCLUSIONS: Caudal DEX attenuated stress response to surgical trauma and
      provided better postoperative analgesia.

PMID- 23545866
TI  - Antifibrinolytics in cardiac surgery.
AB  - Cardiac surgery exerts a significant strain on the blood bank services and is a
      model example in which a multi-modal blood-conservation strategy is recommended.
      Significant bleeding during cardiac surgery, enough to cause re-exploration
      and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis
      is one of the important contributors to increased bleeding. This knowledge has
      led to the use of anti-fibrinolytic agents especially in procedures performed
      under cardiopulmonary bypass. Nothing has been more controversial in recent times
      than the aprotinin controversy. Since the withdrawal of aprotinin from the world
      market, the choice of antifibrinolytic agents has been limited to lysine
      analogues either tranexamic acid (TA) or epsilon amino caproic acid (EACA). While
      proponents of aprotinin still argue against its non-availability. Health Canada
      has approved its use, albeit under very strict regulations. Antifibrinolytic
      agents are not without side effects and act like double-edged swords, the
      stronger the anti-fibrinolytic activity, the more serious the side effects.
      Aprotinin is the strongest in reducing blood loss, blood transfusion, and
      possibly, return to the operating room after cardiac surgery. EACA is the least
      effective, while TA is somewhere in between. Additionally, aprotinin has been
      implicated in increased mortality and maximum side effects. TA has been shown to
      increase seizure activity, whereas, EACA seems to have the least side effects.
      Apparently, these agents do not differentiate between pathological and
      physiological fibrinolysis and prevent all forms of fibrinolysis leading to
      possible thrombotic side effects. It would seem prudent to select the right agent
      knowing its risk-benefit profile for a given patient, under the given
      circumstances.

PMID- 23545867
TI  - Aortic dissection: to be or not to be?
AB  - Patients with acute aortic dissection present with such varied symptoms that
      diagnosis becomes difficult. Various imaging techniques like computed tomography
      angiography (CTA), magnetic resonance imaging and ultrasonography are used to
      diagnose this entity, but they too have their limitations. We present a case,
      which was falsely diagnosed as acute aortic dissection by CTA, which resulted in
      patient undergoing sternotomy.

PMID- 23545868
TI  - Mitral regurgitation jet around neoannulus: mitral valve replacement in
      erysipelothrix rhusiopathiae endocarditis.
AB  - A 50-year-old male presented with erysipelothrix rhusiopathiae (ER) endocarditis
      of the mitral valve, severe mitral regurgitation, and heart failure. The ER
      endocarditis destroyed the native mitral annulus therefore a new annulus was
      created for the suspension of the mitral bioprosthesis. Postoperative neoannulus
      dehiscence and leak prompted to redo surgery where transesophageal
      echocardiography (TEE) played an important role in pointing out the exact
      location of perineoannular leaks for repair.

PMID- 23545869
TI  - An unusual cause of intraoperative acute superior vena cava syndrome.
AB  - Acute intraoperative superior vena cava (SVC) syndrome is an exceedingly rare
      complication in the cardiac surgical population. We describe the case of a 71
      year-old female undergoing multi-vessel coronary artery bypass grafting who
      developed acute intraoperative SVC syndrome following internal thoracic artery
      harvest retractor placement. Her symptoms included severe plethora, facial
      engorgement and scleral edema, which was associated with hypotension and severe
      elevation of central venous pressure. Transesophageal echocardiography was
      crucial in the diagnosis, management, and optimal retractor placement ensuring
      adequate SVC flow. Potential causes of intraoperative SVC syndrome are reviewed
      as well as management options.

PMID- 23545870
TI  - Technology: an aid to clinical judgement.
AB  - Complete removal of renal cell tumor with thrombus which extends above the
      diaphragm often necessitates use of cardiopulmonary bypass. Transesophageal
      echocardiography (TEE) can play an important role in delineating the extent of
      tumor growth. We describe a patient with renal cell carcinoma with thrombosis
      invading into the right ventricle and its complete removal with the aid of TEE.

PMID- 23545871
TI  - Perioperative management of tracheobronchial injury following blunt trauma.
AB  - We describe tracheobronchial injury (TBI) in a 17-year-old teenager following
      blunt trauma resulting from a road traffic accident. The patient presented to a
      peripheral hospital with swelling over the neck and face associated with
      bilateral pneumothorax for which bilateral intercostal drains were inserted and
      the patient was transferred to our institute. Fiber-optic videobronchoscopy (FOB)
      was performed, the trachea and bronchi were visualized, and the site and extent
      of injury was assessed. Spontaneous respiration was maintained till assessment of
      the airway. Then the patient was anesthetized with propofol and paralyzed using
      succinylcholine and a double-lumen endobronchial tube was inserted; thereafter,
      the adequacy of controlled manual ventilation and air-leak through intercostal
      drains was assessed and the patient was transferred to operating room (OR) for
      repair of the airway injury. The OR was kept ready during FOB to manage any
      catastrophe. This case describes the need for proper preparation and
      communication between health care team members to manage all possible scenarios
      of traumatic TBI.

PMID- 23545872
TI  - A rare case of a left atrial hemangioma mimicking a myxoma.
AB  - A 68-year-old gentleman presented with a recent history of exertional dyspnea
      associated with anginal chest pain. Transthoracic echocardiography revealed a
      well-circumscribed mass in the left atrium attached to the inter-atrial septum. A
      provisional diagnosis of left atrial (LA) myxoma was made. Coronary angiography
      revealed significant single-vessel disease. The patient underwent coronary artery
      bypass grafting and resection of the LA tumor. The histopathological diagnosis of
      the tumor came out to be a cardiac hemangioma.

PMID- 23545873
TI  - Cardiac surgery in a patient with immunological thrombocytopenic purpura:
      complications and precautions.
AB  - Immune thrombocytopenic purpura (ITP) patients are at high-risk for bleeding
      complications during and after cardiac surgeries involving cardiopulmonary
      bypass. We report a patient with ITP with severe coronary artery disease and
      mitral valve regurgitation who underwent uncomplicated coronary artery bypass
      grafting and mitral valve replacement. Three weeks later, the patient was
      readmitted in a very low general condition with signs of pericardial tamponade.
      We describe our experience of managing the case.

PMID- 23545874
TI  - Agenesis of the lung.

PMID- 23545875
TI  - Giant aortic root after previous aortic valve replacement.

PMID- 23545876
TI  - In response to, 'Magnets and implantable cardioverter defibrillators'.

PMID- 23545877
TI  - Activated clotting time tube malfunction: a rare cause of heparin overdose.

PMID- 23545878
TI  - Anesthetic implications in Holt-Oram Syndrome.

PMID- 23545879
TI  - An unusual case of high central venous pressure.

PMID- 23545880
TI  - Whistling from deep within!

PMID- 23545881
TI  - Electronic coupling between photo-excited stacked bases in DNA and RNA strands
      with emphasis on the bright states initially populated.
AB  - In biology the interplay between multiple light-absorbers gives rise to complex
      quantum effects such as superposition states that are of extreme importance for
      life, both for harvesting solar energy and likely protecting nucleic acids from
      radiation damage. Still the characteristics of these states and their quantum
      dynamics are a much debated issue. While the electronic properties of single
      bases are fairly well understood, the situation for strands is complicated by the
      fact that stacked bases electronically couple when photoexcited. These newly
      arising states are denoted as exciton states and are simply linear combinations
      of localised wavefunctions that involve N - 1 ground-state bases and one base in
      its excited state (cf. the Frenkel exciton model). There is disagreement over the
      number of bases, N, that coherently couple, i.e., the spatial extent of the
      exciton, and how electronic deexcitation back to the ground state occurs. The
      importance of dark charge-transfer states has been inferred both from time
      resolved fluorescence and transient absorption experiments. These states were
      suggested to be responsible for long deexcitation times but it is unclear whether
      'long' is tens of picoseconds or nanoseconds. In this review paper, we focus on
      the bright states initially populated and discuss their nature based on
      information obtained from systematic absorption and circular dichroism
      experiments on single strands of different lengths. Our results from the last
      five years are compared with those from other groups, and are discussed in the
      context of successive deexcitation schemes. Pieces to the puzzle have come from
      different experiments and theory but a complete description has yet to emerge. As
      such the story about DNA/RNA photophysical decay mechanisms resembles the tale
      about the blind men and the elephant where all see the beast in different,
      correct but incomplete ways. 

PMID- 23545883
TI  - Use of cidofovir in recurrent respiratory papillomatosis.

PMID- 23545884
TI  - Medialization thyroplasty for voice restoration after transoral cordectomy.
AB  - Fourteen dysphonic patients who had previously undergone total or extended
      cordectomy underwent medialization thyroplasty. A minimum delay of 6 months was
      respected to allow the spontaneous "neocord" formation, to evaluate the voice
      recovery achieved by speech therapy alone and to avoid an undiagnosed early
      recurrence. Surgery was performed under general anaesthesia, using a laryngeal
      mask, because undermining the fibrous tissue at the inner side of the thyroid ala
      is a prolonged and difficult procedure. This step was essential to ensure an easy
      placement of the implant and to avoid tearing the fibrous tissue, with subsequent
      risk of implant extrusion. Visual control of the implant implementation was
      obtained by flexible videoendoscopy. The Montgomery((r)) implant system (Boston,
      Westborough, MA) was used for the majority of the cases. Hand-made modified
      Montgomery implants or Gore-tex((r)) were used in case of extended scarring or
      peculiar anatomic defect. The voice assessment showed a decrease of the VHI score
      from 50.5 to 39.4; a decrease of G from 2.4 to 2; an increase of maximum
      phonation time (MPT) from 6.2 to 7.3 s; a decrease of the maximum fundamental
      frequency (Fo-high) from 338.7 to 242.4 Hz and a decrease of the phonation
      quotient from 1,144.9 to 544.9 ml/s. The lower intensity (I-low) remained
      unchanged, from 60 to 58 dB. Statistically significant improvement was noted only
      for VHI and G grading. A decrease of the voice efforts and fatigue were noticed
      by all the patients.

PMID- 23545885
TI  - Expression of stefin A is of prognostic significance in squamous cell carcinoma
      of the head and neck.
AB  - Lysosomal proteases cathepsins B and L (CB, CL) and their endogenous inhibitors
      stefins A and B (SA, SB) are associated with tumor cell invasion and metastasis.
      The purpose of this study was to determine the immunohistochemical (IHC)
      localization of these parameters in tissue sections of 65 patients with operable
      head and neck squamous cell carcinoma (HNSCC) and to evaluate the prognostic
      significance of the observed IHC reactions. In SCC cells, a dot-like staining
      pattern for CB and CL was especially polarized in the perinuclear area and for
      stefins the characteristic IHC pattern was a diffuse cytoplasmic reaction. Higher
      SA immunoreactivity scores were found prognostically advantageous in univariate
      survival analysis [locoregional control (LRC), P = 0.003; disease-free survival
      (DFS), P = 0.023; disease-specific survival (DSS), P = 0.030] and appeared
      significant for predicting LRC (P = 0.019) in a multivariate setting. Among node
      positive extracapsular extension-negative patients, SA positivity correlated with
      a favorable outcome (LRC, P = 0.094; DFS, P = 0.013; DSS, P = 0.012). In
      conclusion, SA immunoreactivity in tumor cells was related to a favorable
      prognosis. In the neck node-positive extracapsular extension-negative subgroup,
      SA immunoreactivity scores can be used to identify patients at increased risk for
      disease relapse.

PMID- 23545886
TI  - Letter to the editor regarding the article by Yazici et al.

PMID- 23545887
TI  - Insulin therapy for challenging patient cases.
AB  - Initiating and advancing insulin therapy in patients with type 2 diabetes
      mellitus can be challenging. However, with the availability of insulin analogs
      with more physiologic profiles, and with the initiation of simple insulin
      regimens (eg, the use of basal insulin administered once daily), an opportunity
      is created to empower patients to self-titrate their insulin. Self-titration can
      reduce the burden on the physician as well as improve glycemic control in
      patients. More options for intensifying insulin now exist, including gradually
      adding prandial insulin (referred to as a basal "plus" strategy) or using
      premixed insulin analogs for patients with relatively consistent lifestyles and
      habits. More-concentrated forms of insulin, such as U-500 insulin, may be helpful
      for patients requiring very large doses of insulin. The key is to match the
      insulin regimen to the patient; engage in dialogue to understand the patient's
      lifestyle, concerns, and skill sets; and develop, through a shared decision
      making process, appropriate individualized treatment recommendations. The present
      review article focuses on the use of insulin replacement therapy in challenging
      patient cases.

PMID- 23545888
TI  - The future of insulin therapy for patients with type 2 diabetes mellitus.
AB  - Insulin therapy has been the mainstay of therapy for patients with type 2
      diabetes mellitus for the past 90 years. This trend is likely to continue as new
      formulations are developed to more closely mimic physiologic insulin secretion
      and to provide patients who have diabetes with more convenient options for
      integrating this therapy into their lifestyle. The present article reviews how
      the role of insulin continues to evolve, from its earlier use in the treatment
      paradigm (even at first diagnosis) to its role in combination therapy with
      incretin-based therapies, as well as new formulations that provide more
      convenient forms of insulin replacement therapy.

PMID- 23545889
TI  - Insulin therapy in type 2 diabetes mellitus: history drives patient care toward a
      better future.
AB  - "Insulin will never be a success in the treatment of diabetics without the aid of
      the general practitioner."(1) These words, written by Elliott P. Joslin, MD, in
      1923, still ring true today. After the first successful insulin injection was
      administered on January 23, 1922, to Leonard Thompson, a 14-year-old patient with
      type 1 diabetes mellitus at Toronto General Hospital, it did not take long before
      a diabetes clinic using insulin treatment was set up.(2) Insulin was subsequently
      provided to physicians in the United States for clinical trials, although many US
      patients with diabetes mellitus presented themselves to Sir Frederick Banting,
      MD, co-discover of insulin, in Toronto for insulin treatment. Within 2 years,
      insulin was being manufactured by multiple pharmaceutical companies and was
      available commercially in both the United States and Canada.(2) Almost
      immediately, health care professionals and others identified the problem of who
      was going to care for all of these patients. Patients were arriving at diabetes
      clinics expecting to receive insulin, often overwhelming the few physicians who
      were educated on the care of diabetic patients. For this reason, the physicians
      and nurses at the New England Deaconess Hospital in Boston initiated a teaching
      program so that general practitioners could learn all aspects of the management
      of diabetes.

PMID- 23545892
TI  - A heterogeneous palladium catalyst hybridised with a titanium dioxide
      photocatalyst for direct C-C bond formation between an aromatic ring and
      acetonitrile.
AB  - A palladium catalyst hybridised with a titanium dioxide photocatalyst can promote
      cyanomethylation of an aromatic ring by using acetonitrile, where the
      photocatalyst activates acetonitrile to form a cyanomethyl radical before the C-C
      bond formation using the palladium catalyst.

PMID- 23545891
TI  - Identifying and addressing barriers to insulin acceptance and adherence in
      patients with type 2 diabetes mellitus.
AB  - Progressive hyperglycemia is a characteristic of type 2 diabetes mellitus (T2DM)
      that poses a challenge to maintaining optimal glycemic control. Achieving
      glycemic control early in the course of disease can minimize or prevent serious
      complications. Most patients with T2DM eventually require insulin replacement
      therapy to attain and preserve satisfactory glucose control. For decades, the use
      of insulin to address the primary defect of T2DM has been a cornerstone of
      diabetes therapy. Insulin is indicated for patients with T2DM presenting with
      clinically significant hyperglycemia, and it is mandatory for patients exhibiting
      signs of catabolism. Insulin should be considered for patients in whom
      hyperglycemia persists despite attempts to control the condition through diet and
      exercise modifications and the use of noninsulin therapies. Many physicians delay
      initiation of insulin until absolutely necessary, sometimes overestimating
      patient concerns about its use. Modern insulin analogs, treatment regimens, and
      delivery devices make insulin more user friendly, and physicians can promote
      patient acceptance of insulin by reviewing the benefits of controlled glycated
      hemoglobin levels and addressing patient concerns.

PMID- 23545895
TI  - The long and winding helix.

PMID- 23545893
TI  - Adult mortality in a randomized trial of mass azithromycin for trachoma.

PMID- 23545896
TI  - Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in
      obsessive-compulsive disorder.
AB  - Numerous studies have reported on pharmacogenetics of antidepressant response in
      depression. In contrast, little is known of response predictors in obsessive
      compulsive disorder (OCD), a disorder with among the lowest proportion of
      responders to medication (40-60%). Our study is the largest investigation to date
      (N=184) of treatment response and side effects to antidepressants in OCD based on
      metabolizer status for CYP2D6 and CYP2C19. We observed significantly more failed
      medication trials in CYP2D6 non-extensive compared with extensive metabolizers
      (P=0.007). CYP2D6 metabolizer status was associated with side effects to
      venlafaxine (P=0.022). There were nonsignificant trends for association of CYP2D6
      metabolizer status with response to fluoxetine (P=0.056) and of CYP2C19
      metabolizer status with response to sertraline (P=0.064). Our study is the first
      to indicate that CYP genes may have a role in antidepressant response in OCD.
      More research is required for a future clinical application of genetic testing,
      which could lead to improved treatment outcomes. 

PMID- 23545898
TI  - Clinical significance of keratinocyte growth factor and K-sam gene expression in
      gastric cancer.
AB  - Although gastric cancer is increasingly being detected at an early stage of
      development, diffuse growth-type malignant tumors, such as scirrhous gastric
      cancer, are usually at an advanced stage at the time of diagnosis, resulting in
      poor treatment outcomes. The aim of this study was to determine whether the K-sam
      gene and keratinocyte growth factor (KGF) expression may be used to identify
      malignant tumors with a poor prognosis. K-sam and KGF expression was
      retrospectively evaluated in samples from 86 patients with early and advanced
      gastric cancer according to type, by examining serum levels and using
      immunohistochemical staining. The associations with clinicopathological
      characteristics and survival were also examined. The mean serum KGF levels were
      11.191+/-3.808 pg/ml in early stage and 10.715+/-3.4991 pg/ml in advanced gastric
      cancer patients. KGF levels were significantly higher in types 4 and 5 (14.498+/
      3.812 pg/ml, n=6) compared with types 1, 2 and 3 (10.747+/-3.571 pg/ml, n=80;
      P=0.028). Stage classification was identified as the only significant factor
      which determined overall survival. Patients with KGF-positive tumors had
      significantly higher serum KGF levels compared with those who had KGF-negative
      tumors. Patients with K-sam-positive tumors had significantly higher KGF levels
      compared with those who had K-sam-negative tumors. Pathological KGF expression
      was not significantly correlated with the degree of differentiation; however,
      there was a positive correlation between high K-sam expression in scirrhous
      gastric tumors and serum KGF levels. The present study revealed that high serum
      KGF levels are a risk factor for diffuse infiltrative gastric cancer and may
      provide a simple method of identifying patients with a poor prognosis among
      previously diagnosed preoperative gastric cancer patients.

PMID- 23545899
TI  - Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the
      mitochondrial pathway.
AB  - Brain glioma is the most common malignant intracranial tumor and has become the
      focus of research on diseases of the central nervous system due to its high
      incidence and poor prognosis. As a small-molecule inhibitor of X-linked inhibitor
      of apoptosis protein (XIAP), embelin has the ability to specifically inhibit XIAP
      to control and regulate the apoptosis of various types of tumor cells. However,
      to date, the mechanism of action for this effect is not well understood. The aim
      of this study was to investigate the role that the mitochondrial pathway plays in
      embelin-induced brain glioma cell apoptosis and the effect of embelin on the cell
      cycle. Brain glioma cells were treated with different doses of embelin. The MTT
      method was used to determine cell proliferation, and flow cytometry was used to
      determine apoptosis, as well as changes in the cell cycle and cell mitochondrial
      membrane potential. Western blot analysis was performed to determine the
      expression levels of apoptosis-associated proteins, Bcl-2, Bcl-xL, Bax and Bak as
      well as cytochrome c. We found that embelin induced a time- and dose-dependent
      apoptosis of brain glioma cells, and that it could arrest the cell cycle in the
      G0/G1 phase. Embelin also caused changes in brain glioma cell mitochondrial
      membrane potential. Additionally, embelin regulated the shifting of Bax and Bcl-2
      to promote the mitochondrial release of cytochrome c, thus activating the caspase
      proteins to cause apoptosis. Thus, embelin induces apoptosis in brain glioma
      cells which is closely associated with the mitochondrial pathway.

PMID- 23545897
TI  - Genetic variants associated with methotrexate efficacy and toxicity in early
      rheumatoid arthritis: results from the treatment of early aggressive rheumatoid
      arthritis trial.
AB  - Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe
      rheumatoid arthritis (RA), but individual variation in treatment response remains
      unexplained. We tested the associations between 863 known pharmacogenetic
      variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid
      Arthritis Trial participants with early RA. Efficacy and toxicity were modeled
      using multiple regression, adjusted for demographic and clinical covariates.
      Penalized regression models were used to test joint associations of markers
      and/or covariates with the outcomes. The strongest genetic associations with
      efficacy were in CHST11 (five markers with P<0.003), encoding carbohydrate
      (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity
      were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes
      SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The
      selected markers explained a consistently higher proportion of variation in
      toxicity than efficacy. These findings could inform future development of
      personalized therapeutic approaches. 

PMID- 23545900
TI  - Beneficial influence of topical extra virgin olive oil application on an
      experimental model of penile fracture in rats.
AB  - Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of
      corpus cavernosum. In this study, we aimed to investigate the healing influence
      of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some
      oxidative stress biomarkers for the first time. Histopathological evaluation was
      also realized. A total of 18 male Sprague-Dawley albino rats were divided into
      three groups of six rats each as control group, in PF (alone) group, and PF +
      EVOO group. Experimental PF was formed via incising from the proximal dorsal side
      of the penis in the rats of all groups except control. While in PF (alone) group,
      fracture was formed and the incision was primarily closed, in PF + EVOO group in
      addition to foregoing processes, EVOO was also administrated topically twice a
      day for 3 weeks. At the end of the experiment, all rats were killed and penectomy
      was carried out. While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and
      total oxidant status significantly (p < 0.05) increased, reduced glutathione and
      total free sulfhydryl groups markedly (p < 0.05) decreased in PF (alone) group
      when compared with PF + EVOO group. Levels of these parameters were reversed to
      nearly normal values by topical EVOO application. Protection by EVOO is further
      substantiated via the improved histological findings in PF + EVOO group as
      against degenerative changes in the rats of PF (alone) group. Our data revealed
      that EVOO has protective effect in penile cavernosal tissue through probably its
      antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects.

PMID- 23545901
TI  - GABAA receptor-binding protein promotes sensitivity to apoptosis induced by
      chemotherapeutic agents.
AB  - In the present study, the expression of human gamma-aminobutyrate type A (GABAA)
      receptor-binding protein (GABARBP) is downregulated in ovarian cancer cell lines
      and tissues. We also found that the specific function of GABAPBP was that of a
      novel pro-apoptotic protein. Both GABARBP and cisplatin suppressed cancer cell
      proliferation in a concentration-dependent manner. The combined treatment of
      GABARBP and cisplatin was more effective in inhibiting cell growth, as well as
      cell migration, than with either drug treatment alone. At the same time, the
      treatment combination is correlated with the downregulation of cyclin D1 and
      CDK4, arrested cell cycle progression in the G0-G1 phase and enhancing p53
      expression, while also reducing Bcl-2 and Bcl-xL expression. The p53 and p21
      promoter luciferase activities were induced by GABARBP, whereas there was no
      effect on the p53-/- and p21-/- system. In addition, p53 activity was validated
      with UV irradiation and siGABARBP. Taken together, our results indicate that
      GABARBP can regulate the pro-apoptotic activity of cisplatin via the upregulation
      of p53 expression.

PMID- 23545903
TI  - Service utilization for mental problems in a metropolitan migrant population in
      china.
AB  - OBJECTIVE: The purpose of this study was to investigate the prevalence and
      predictors of service utilization for mental health problems of the first
      generation migrant population in Shenzhen, China, a city that attracts millions
      of unskilled rural laborers each year. METHODS: Using the structured World Mental
      Health Composite International Diagnostic Interview, the investigators conducted
      face-to-face surveys between September 1, 2005, and January 30, 2006. A total of
      7,134 respondents age 18 years and above finished the surveys. The main outcomes
      were prevalence of mental disorders according to DSM-IV criteria, as well as
      prevalence of mental health services used in different sectors. RESULTS: Nine
      percent of the sample had ever used some type of service for mental health
      issues, and 6.3% used services outside of the health service sector, such as
      human services and complementary and alternative medicine. In addition, DSM
      criteria for a mental disorder over the lifetime were met by 18.1% of
      respondents; of the respondents with a mental disorder, 18.3% had used mental
      health services at least once. Migrants who were unmarried, had high family
      income, were raised in metropolitan areas, had histories of homelessness or
      attempted suicide, had a psychotic disorder, or had an anxiety disorder were more
      likely to use services for mental health care. CONCLUSIONS: In Shenzhen, few
      migrants used mental health services and most used complementary and alternative
      medicine services. Future studies of service utilization patterns in migrant
      populations should give special attention to personal characteristics, such as
      family support.

PMID- 23545905
TI  - Eye wall resections for intraocular tumors: our experience.
AB  - We conducted a retrospective review of 11 eyes undergoing eye wall resection
      between October 1998 and October 2009. The median age of 11 patients was 29
      years. Decreased vision (eight) was the most common presenting symptom. Ciliary
      body medulloepithelioma was the most common clinical diagnosis (six).
      Medulloepithelioma was the most common histopathological diagnosis (four). The
      duration of follow-up ranged from 0.5 to 67 months (median 11 months). Three eyes
      needed to be enucleated in the postoperative period (margin involvement two eyes,
      recurrence one eye). Postoperative complications among others included retinal
      detachment (three), vitreous hemorrhage (three), cataract (two), and
      suprachoroidal hemorrhage (two). To conclude, prognosis of this procedure
      continues to be guarded needing close postoperative follow-up. 

PMID- 23545904
TI  - Assessing the order of critical alterations in prostate cancer development and
      progression by IHC: further evidence that PTEN loss occurs subsequent to ERG gene
      fusion.
AB  - BACKGROUND: ERG rearrangements and PTEN (phosphatase and tensin homolog deleted
      on chromosome 10) loss are two of the most common genetic alterations in prostate
      cancer. However, there is still significant controversy regarding the order of
      events of these two changes during the carcinogenic process. We used
      immunohistochemistry (IHC) to determine ERG and PTEN status, and calculated the
      fraction of cases with homogeneous/heterogeneous ERG and PTEN staining in a given
      tumor. METHODS: Using a single standard tissue section from the index tumor from
      radical prostatectomies (N=77), enriched for relatively high grade and stage
      tumors, we examined ERG and PTEN status by IHC. We determined whether ERG or PTEN
      staining was homogeneous (all tumor cells staining positive) or heterogeneous
      (focal tumor cell staining) in a given tumor focus. RESULTS: Fifty-seven percent
      (N=44/77) of tumor foci showed ERG positivity, with 93% of these (N=41/44) cases
      showing homogeneous ERG staining in which all tumor cells stained positively.
      Fifty-three percent (N=41/77) of tumor foci showed PTEN loss, and of these 66%
      (N=27/41) showed heterogeneous PTEN loss. In ERG homogeneously positive cases,
      any PTEN loss occurred in 56% (N=23/41) of cases, and of these 65% (N=15/23)
      showed heterogeneous loss. In ERG-negative tumors, 51.5% (N=17/33) showed PTEN
      loss, and of these 64.7% (N=11/17) showed heterogeneous PTEN loss. In a subset of
      cases, genomic deletions of PTEN were verified by fluorescence in situ
      hybridization in regions with PTEN protein loss as compared with regions with
      intact PTEN protein, which did not show PTEN genomic loss. CONCLUSIONS: These
      results support the concept that PTEN loss tends to occur as a subclonal event
      within a given established prostatic carcinoma clone after ERG gene fusion. The
      combination of ERG and PTEN IHC staining can be used as a simple test to
      ascertain PTEN and ERG gene rearrangement status within a given prostate cancer
      in either a research or clinical setting.

PMID- 23545906
TI  - Evaluation of the efficacy, tolerability, and safety of an over-the-counter acne
      regimen containing benzoyl peroxide and salicylic acid in subjects with acne.
AB  - Benzoyl peroxide (BPO) is a widely used over-the-counter (OTC) topical acne
      treatment often used in combination with salicylic acid (SA) to achieve better
      comedone control than that achieved with BPO alone. MaxClarityTM is an OTC acne
      treatment system comprising BPO and SA in an aqueous foam delivery vehicle,
      VersaFoam AFTM. This paper describes 2 open-label, single-arm studies conducted
      to assess the efficacy, safety, tolerability, and patient preference of
      MaxClarity in the treatment of mild, moderate, and severe acne. Subjects applied
      MaxClarity twice daily for 8 weeks in study 402 and for 12 weeks in study 405.
      Reductions in all lesion types were seen throughout both studies. At week 8
      (study 402), there was a mean reduction from baseline of -56.9 +/- 32.7% in total
      lesions in subjects with mild, moderate, or severe acne. At week 12 (study 405),
      there was a reduction from baseline of -61.6 +/- 22.0% in total lesions in
      subjects with moderate or severe acne. Overall, both studies demonstrated that
      MaxClarity is a generally well tolerated and effective treatment for mild,
      moderate, and severe acne.

PMID- 23545907
TI  - Comparison of clindamycin 1% and benzoyl peroxide 5% gel to a novel composition
      containing salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric
      acid, and dioic acid in the treatment of acne vulgaris.
AB  - This study evaluated the tolerance and efficacy of 2 facial skin products in
      subjects with acne using the following acne treatments: 1) treatment A, a
      combination of salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid,
      citric acid, and dioic acid, and 2) treatment B (BenzaClin(r), clindamycin 1% and
      benzoyl peroxide 5% gel). The treatment design included the split-face
      application of treatment A and treatment B and the full-face application of the
      cleanser, moisturizer, and sunscreen. Data were collected through physician
      visual assessments, subject irritation questionnaires and assessments, along with
      clinical photography. Results showed similar tolerance and efficacy for both
      treatments.

PMID- 23545908
TI  - Comparison of a skin-lightening cream targeting melanogenesis on multiple levels
      to triple combination cream for melasma.
AB  - The safety and efficacy of a novel skin-lightening cream (SLC) with 4%
      hydroquinone (HQ), which additionally contains 4 skin-brightening actives, was
      compared with a triple combination cream (TCC) with 4% HQ, 0.05% tretinoin, and
      0.01% fluocinolone acetonide for the treatment of melasma under measures of sun
      protection. The study was a randomized, investigator-blinded, split-face study
      including 20 Caucasian females with at least mild epidermal or mixed melasma.
      Evaluations were made before treatment, after 4 and 8 weeks, and after 12 weeks
      at the end of the once-daily treatment period with the creams. The evaluations
      included the investigator's tolerability assessments, the Investigator's Global
      Assessment, the Melasma Area and Severity Index (MASI), and a participant
      questionnaire. Under the conditions of the present study, the SLC was comparable
      in both efficacy and tolerability with the well-established TCC treatment for
      facial melasma. The MASI reduction became significant for both creams after 4
      weeks and reached -77% for SLC and -79% for TCC cream after 12 weeks of once
      daily use under measures of sun protection. None of the subjects discontinued
      treatment because of an intolerability or adverse event. About one-third of the
      subjects experienced at least one local intolerability (eg, erythema, dryness, or
      peeling) with both creams over the entire study period, while the remaining
      subjects did not experience any intolerabilities.

PMID- 23545909
TI  - Efficacy and safety of tretinoin 0.025%/clindamycin phosphate 1.2% gel in
      combination with benzoyl peroxide 6% cleansing cloths for the treatment of facial
      acne vulgaris.
AB  - Combination therapy using medications with complementary mechanisms of action is
      the standard of care in treating acne. We report results of a clinical trial
      evaluating the use of a fixed-dose tretinoin 0.025%/clindamycin phosphate 1.2%
      (T/CP) gel in combination with a benzoyl peroxide 6% foaming cloth compared with
      T/CP alone for facial acne. At week 12, the combination therapy group showed a
      trend toward greater efficacy compared with T/CP alone. There was a high success
      rate observed in the study, which may be attributable to the large percentage of
      adult female acne patients enrolled. Cutaneous adverse events were not
      statistically different in using combination therapy compared with T/CP alone.

PMID- 23545910
TI  - Scoping scalp disorders: practical use of a novel dermatoscope to diagnose hair
      and scalp conditions.
AB  - BACKGROUND: Dermoscopy has been widely implemented to diagnose various skin and
      scalp disorders. However, existing devices that call for direct scalp contact may
      alter the appearance of hair features or perifollicular structures. OBJECTIVE:
      This paper will show how the Canfield DermScope can quickly and easily identify
      various nonscarring and scarring scalp disorders. Its open design does not change
      the direction of affected hairs or blanch certain features such as erythema.
      Features like perifollicular hyperkeratosis and loss of follicular orifices are
      still easily visible. METHODS AND MATERIALS: The author prospectively
      photographed patients with hair and scalp disorders in private practice between
      2011 to 2012 using the handheld Canfield DermScope device. RESULTS: The presence
      of scale, erythema, tufting, miniaturized or broken hairs, and loss of follicular
      orifices were quickly identified to make a diagnosis. CONCLUSION: The diagnosis
      of hair and scalp disorders can be greatly facilitated by the use of the
      DermScope device.

PMID- 23545911
TI  - Efficacy of extended-release 45 mg oral minocycline and extended-release 45 mg
      oral minocycline plus 15% azelaic acid in the treatment of acne rosacea.
AB  - Rosacea is one of the most commonly occurring dermatoses treated by
      dermatologists. There are multiple therapeutic options available for the
      treatment of papulopustular rosacea. Rosacea is an inflammatory condition,
      classically presenting with flushing and/or blushing along with erythema, edema,
      telangiectasia, papules, pustules, and nodules of the face. Minocycline, a member
      of the tetracycline family, has demonstrated benefit in the treatment of
      inflammatory lesions in patients with rosacea. This manuscript highlights the use
      of a new sustained-release low-dose minocycline 45 mg tablet, with or without
      azelaic acid, for the treatment of papulopustular rosacea.

PMID- 23545912
TI  - A multicenter, randomized, double-blind study of the efficacy and safety of
      calcipotriene foam, 0.005%, vs vehicle foam in the treatment of plaque-type
      psoriasis of the scalp.
AB  - BACKGROUND: Calcipotriene ointment and cream are effective treatments for
      psoriasis, but many patients with scalp psoriasis prefer lighter, less messy
      vehicles. OBJECTIVES: To evaluate the efficacy and safety of calcipotriene foam,
      0.005%, for plaque-type psoriasis of the scalp. METHODS: Subjects (n=363) were
      randomized into an 8-week, multicenter, double-blind, vehicle-controlled,
      parallel-group, phase 3b study of calcipotriene foam, 0.005% (NCT01139580).
      Primary end point was the proportion of subjects with an Investigator's Static
      Global Assessment (ISGA) score of 0 (clear) or 1 (almost clear) at week 8 for
      scalp involvement. Body involvement, target lesion score, and improvement for
      erythema, scaling, and plaque thickness were also assessed.<BR> RESULTS: At week
      8, more subjects in the calcipotriene foam, 0.005% group (40.9%) met the primary
      end point vs the vehicle foam group (24.2%; intent-to-treat [ITT] population; P
      <.001); a significant difference between groups was also observed at weeks 2 (P =
      .041) and 4 (P <.001). No significant difference was observed between treatment
      groups for ISGA of body psoriasis (ITT population; P = .544). In the per-protocol
      population, but not the ITT population, more subjects in the calcipotriene foam,
      0.005%, group than the vehicle foam group met the secondary end points for
      scaling (P = .019) and plaque thickness (P =.027). Incidence of adverse events in
      both treatment groups was low; calcipotriene foam, 0.005%, was associated with
      erythema. LIMITATIONS: An 8-week study provides limited safety and efficacy
      data.<BR> CONCLUSION: Calcipotriene foam, 0.005%, was more effective than vehicle
      foam for improving scalp psoriasis over an 8-week period, with improvements
      evident from week 2, and had a similar safety profile to vehicle foam.

PMID- 23545913
TI  - Topical amitriptyline combined with ketamine for the treatment of
      erythromelalgia: a retrospective study of 36 patients at Mayo Clinic.
AB  - BACKGROUND: Erythromelalgia is an uncommon neurovascular disorder characterized
      by redness, increased skin temperature, and pain that usually occurs in the
      extremities. Treatment remains challenging because of its varying response to
      medical therapy. The objective of this study was to assess the response of
      erythromelalgia to compounded topical amitriptyline-ketamine. METHODS: We
      retrospectively evaluated 36 patients with erythromelalgia who were treated with
      compounded topical amitriptyline-ketamine from January 1, 2004, through January
      31, 2011. RESULTS: Thirty-two patients (89%) were female. Mean (standard
      deviation) age was 44.7 (15.8) years (range, 5-74 years). Patients applied the
      medication 1 to 6 times per day (median, 5 times). One patient (3%) had complete
      relief from symptoms, 14 (39%) had substantial relief, 12 (33%) had some relief,
      7 (19%) had no relief, and 2 (6%) had local worsening of symptoms. No patients
      had systemic adverse effects. CONCLUSIONS: A majority of patients with
      erythromelalgia (75%) reported improvement in pain with topical application of a
      compounded amitriptyline-ketamine formulation. The medication was well tolerated.

PMID- 23545914
TI  - Efficacy of topical 4% Quassia amara gel in facial seborrheic dermatitis:a
      randomized, double-blind, comparative study.
AB  - BACKGROUND: Seborrheic dermatitis (SD) is a chronic mild skin disorder with high
      prevalence. Various treatment options are available, including topical
      antifungals and anti-inflammatories. Antifungal and anti-inflammatory properties
      of Quassia amara have been reported. AIM: To check the efficacy and safety of a
      topical gel with 4% Quassia amara extract and compare it with topical 2%
      ketoconazole and 1% topical ciclopiroxolamine in the treatment of facial SD.
      METHODS: A group of 60 patients displaying facial SD were randomly distributed in
      3 groups and given either a topical gel with 4% Quassia amara extract, a topical
      gel with 2% ketoconazole, or a topical gel with 1% ciclopirox olamine for 4
      weeks. Disease severity was assessed at the start and weekly along treatment, as
      well as 4 weeks after the end of treatment. In each selected area, severity of
      erythema, scaling, pruritus, and papules were scored from 0 to 3, the sum of
      these values representing the score of SD on the face. This evaluation was
      conducted at each visit. The decrease in SD score with all 3 products was
      compared at each visit. At each stage, overall improvement, safety, and
      tolerability were also assessed. RESULTS: Of the 60 patients, 54 (90%) completed
      the study. The 3 therapeutic options resulted to be very effective, with a
      significant advantage in efficacy for 4% Quassia extract. For the other 2 drugs,
      the results were in line with those previously published in the literature.
      CONCLUSION: Topical gel with 4% Quassia extract represents a new, safe, and
      effective treatment for facial SD.

PMID- 23545915
TI  - The efficacy of ustekinumab in psoriasis.
AB  - Psoriasis is an immune-mediated cutaneous disease affecting 2% of the worldwide
      population. While topical therapy, phototherapy, oral systemic therapy, and
      biologic agents have been used, the treatment of psoriasis still remains a
      challenge. Ustekinumab is a biologic therapy that provides a novel avenue for
      management by blocking interleukin-12/23. The purpose of this article is to
      review the mechanism of action of ustekinumab and its efficacy in psoriatic
      patients. The use of ustekinumab in other immune-mediated diseases is also
      discussed. It is our goal to provide dermatologists with the knowledge to enable
      them to incorporate ustekinumab into their practice.

PMID- 23545916
TI  - Study to evaluate the aesthetic clinical impact of an autologous antiaging serum.
AB  - Since ancient times, humans have fought a still-unwinnable battle against aging
      and time. The possibility of processing our own blood in order to obtain certain
      precious substances for a particular purpose has opened the gates for the
      development of new treatments, indications, and techniques. In this study, we
      obtained an autologous serum with very high concentrations of some growth factors
      and anti-inflammatory cytokines using a special syringelike device that exposed
      the blood to medical-grade glass spheres in a closed system. The application of
      this autologous conditioned antiaging serum achieved local beauty enhancement
      results by improving skin hydration, smoothness, and elasticity.

PMID- 23545917
TI  - A randomized, double-blind phase 4 study of the efficacy and safety of ethanol
      free clobetasol propionate foam, 0.05%, vs vehicle foam in the treatment of
      chronic hand dermatitis.
AB  - BACKGROUND: Chronic hand dermatitis may have a significant detrimental effect on
      daily home-related and work-related activities, and quality of life (QOL).
      Clobetasol propionate foam, 0.05%, is indicated for the treatment of inflammatory
      and pruritic manifestations of corticosteroid-responsive dermatoses in patients
      aged 12 years and older. OBJECTIVES: To demonstrate superior efficacy, similar
      safety, and superior QOL outcomes in subjects with moderate to severe chronic
      hand dermatitis following treatment with clobetasol propionate foam, 0.05%,
      compared with vehicle foam. METHODS: In this randomized, double-blind, vehicle
      controlled, parallel-group, multicenter study (ClinicalTrials.gov identifier
      NCT01323673), subjects aged 12 years and older with moderate to severe chronic
      hand dermatitis and an Investigator's Static Global Assessment (ISGA) score of 3
      or 4 at baseline were randomized 1:1 to receive clobetasol propionate foam,
      0.05%, or vehicle foam, twice daily over 15 days. The primary end point was the
      proportion of subjects who achieved treatment success, defined as improvement
      from baseline of >= 2 ISGA grades for the target hand at day 15. RESULTS: In
      total, 125 subjects were enrolled: 62 subjects were randomized to the clobetasol
      propionate foam group and 63 subjects were randomized to the vehicle foam group.
      The proportion of subjects with treatment success at day 15 did not differ
      significantly between treatment groups. Adverse events (AEs) were reported in 18%
      of subjects in the clobetasol propionate foam group and 8% of subjects in the
      vehicle foam group. No serious AEs, AEs resulting in discontinuation of study
      product, or severe AEs were reported in the clobetasol propionate foam group.
      CONCLUSIONS: Clobetasol propionate foam, 0.05%, was not significantly more
      efficacious than vehicle foam at improving chronic hand dermatitis on
      investigator-assessed end points. Emollient properties of the study product
      vehicle may be a confounder in the study.

PMID- 23545918
TI  - Topical formulation engendered alteration in p53 and cyclobutane pyrimidine dimer
      expression in chronic photodamaged patients.
AB  - While the clinical attributes of photoaging are well characterized in the
      literature, the pathogenic mechanisms that underlie these changes are
      incompletely elucidated. At the molecular level, p53 tumor-suppressor gene
      product mediated excision repair of ultraviolet (UV)-induced DNA damage is a
      critical effector in xeroderma pigmentosum (XP) and potentially in conventional
      photoaging. We examined p53 activity and measured UV-induced DNA damage via
      cyclobutane pyrimidine dimers (CPDs) quantitatively in 20 volunteers before and
      after an 8-week, open-label prospective topical application of a proprietary DNA
      recovery serum (Celfix). There was a statistically significant decrease in
      immunohistochemically determined p53 and CPD levels. While these data are
      preliminary, the findings lend support to the theoretical possibility of a
      topical agent reversing the effects of photodamage at the molecular level and,
      potentially, an ameliorative outcome clinically.

PMID- 23545919
TI  - Surgical corner:a poliglecaprone 25-only approach to wound closure:cosmetic and
      financial advantages.
AB  - The primary concerns when performing surgical excisions include adequate control
      of surgical margins and cosmetic outcome. The ideal repair combines perfect wound
      approximation, tensile strength, and minimal scarring. Various techniques and
      suture materials are utilized by dermatologic surgeons to achieve this goal. We
      describe a Monocryl-only bilayered repair, which can lead to excellent cosmetic
      results and may reduce the burden of return visits for patients. In this paper,
      we describe the technique used to place deep Monocryl sutures, as well as a
      running subcuticular suture, and illustrate this technique with photographs.

PMID- 23545920
TI  - Pterygium inversum unguis: report of an extensive case with good therapeutic
      response to hydroxypropyl chitosan and review of the literature.
AB  - Pterygium inversum unguis is a rare but not exceptional dermatological condition,
      with few descriptions in literature. It occurs more frequently in females and may
      be associated with several clinical conditions. About 50% of cases are concurrent
      with collagen diseases such as systemic lupus erythematosus and scleroderma.
      Severe cases are accompanied by moderate morbidity caused by discomfort when the
      patient has to perform minor tasks. The treatment has been considered complex,
      regardless of its underlying cause, with poor response to the topical therapies
      such as keratolytics and corticosteroids. This paper reports a case of pterygium
      inversum unguis with a good therapeutic response to hydroxypropyl chitosan and
      includes a review of the literature.

PMID- 23545921
TI  - Sustained clinical resolution of acquired epidermodysplasia verruciformis in an
      immunocompromised patient after discontinuation of oral acitretin with topical
      imiquimod.
AB  - Increased cases of acquired epidermodysplasia verruciformis (EDV) have been
      reported in patients with human immunodeficiency virus (HIV). With regard to
      management, there are no randomized controlled trials in either immunocompetent
      or immunocompromised patients, and only a limited number of anecdotal treatment
      options. Systemic retinoids, either independently or in combination with other
      treatment modalities, have been used with limited success, demonstrating
      transient clinical response and recurrence of lesions after cessation of therapy.
      We report a case of an HIV-positive patient with acquired EDV who achieved
      sustained clinical resolution even after discontinuation of oral acitretin by
      applying topical imiquimod to prevent recurrence of his lesions.

PMID- 23545922
TI  - Mycobacterium mucogenicum infection following a cosmetic procedure with poly-L
      lactic acid.
AB  - The emphasis on the preservation of youth is ever apparent as new antiaging
      products, cosmetic procedures, and advertising campaigns aim to address new ways
      to prevent the natural aging process. Many individuals prefer noninvasive
      surgical procedures involving minimal downtime and a speedy recovery. Although
      these cosmetic procedures are considered minor, complications do arise and
      infections can occur. While many species of bacteria can cause these infections,
      one such species that is usually over looked and can cause these infections are
      the atypical mycobacteria. Early diagnosis is important, as these infections can
      rapidly progress into more serious skin manifestations. We present a 31-year-old
      female with a 3-month history of a nonhealing ulcer on her cheek that started
      approximately 2 weeks following a cosmetic procedure with an injectable filler.
      This patient represents an uncommon complication that may occur in patients
      subjected to multiple facial injections, as their susceptibility to infection and
      secondary biofilm formation increases with their current and future injections.
      This case review highlights the growing number of cosmetic procedures in our
      society, the most common complications of these treatments, an emerging
      complication concerning the formation of biofilms, as well as a review of the
      literature on atypical mycobacteria infections.

PMID- 23545923
TI  - Use of lenalidomide in treating refractory prurigo nodularis.
AB  - Prurigo nodularis is a chronic, relapsing neurodermatitis that is often resistant
      to standard therapies with topical corticosteroids and oral antihistamines.
      Thalidomide, while efficacious in treating recalcitrant cases of prurigo
      nodularis, causes significant toxicity. Thalidomide-induced peripheral neuropathy
      frequently results in drug discontinuation. Lenalidomide (Revlimid; Celgene
      Corporation, Summit, NJ) is a derivative of thalidomide with less neurotoxicity
      approved for the treatment of multiple myeloma and myelodysplastic syndromes that
      has not been widely studied in dermatologic disorders. Here, we report a case of
      refractory prurigo nodularis effectively treated with lenalidomide. Given its
      favorable side-effect profile, lenalidomide may offer a superior alternative to
      thalidomide in the treatment of this condition.

PMID- 23545924
TI  - Nd:YAG laser hair removal in Fitzpatrick skin types IV to VI.
AB  - Safe and effective laser treatments are crucial, especially in darker-skinned
      individuals. Herein, we report our experience treating Fitzpatrick skin types IV
      to VI with a long-pulsed, 1,064-nm neodymium-doped yttrium aluminum garnet laser.
      With the right treatment settings, darkly pigmented individuals can undergo laser
      hair removal effectively.

PMID- 23545925
TI  - Infections associated with the use of tumor necrosis factor-alpha inhibitors in
      psoriasis.
AB  - Tumor necrosis factor (TNF)-alpha inhibitors have been shown to increase the
      risks of overall infection and serious infection in rheumatoid arthritis.
      However, it is uncertain whether we can draw the same conclusion in the psoriatic
      population. This article focuses on the 3 most commonly used TNF-alpha inhibitors
      in psoriasis: adalimumab, etanercept, and infliximab. In order to assess the
      risks of overall infection and serious infection in patients with psoriasis, we
      reviewed the underlying mechanism of the potential infection risk, different
      types of serious infection associated with TNF-alpha inhibitors, and current
      evidence in the psoriatic population. Results from 11 randomized controlled
      trials and open-label extension studies showed that there was no apparent
      significant association between the use of TNF-alpha inhibitors and increasing
      risks of overall infection and serious infection. Because of the limitations of
      current evidence, large, long-term follow-up studies with appropriate control
      groups using real-life data, such as postmarket surveillance, are warranted.

PMID- 23545926
TI  - The evaluation of hyaluronic acid, with and without lidocaine, in the filling of
      nasolabial folds as measured by ultrastructural changes and pain management.
AB  - BACKGROUND: Pain management is an important objective in procedures involving
      dermal fillers composed of hyaluronic acid (HA). OBJECTIVE: To compare the 1-year
      clinical results of filling the nasolabial fold with 2 types of filler: large-gel
      particle HA and large-gel particle HA plus 0.3% lidocaine (HA+L). We compared the
      level of pain during treatment and 10 minutes after treatment and assessed the
      safety and efficacy profile, satisfaction, and histological findings (using
      reflectance confocal microscopy [RCM]). MATERIALS AND METHODS: We performed a
      comparative, parallel-group, double-blind trial with an external observer
      (blinded to the type of treatment administered). The filler was applied to the
      nasolabial fold in 119 patients (HA in 62 patients and HA+L in 57). Patients were
      followed at months 3, 9, and 12. Pain was evaluated using a visual analog scale.
      Efficacy and satisfaction were evaluated using the Wrinkle Severity Rating Scale
      and the Global Aesthetic Improvement Scale. RCM images (n=32) were taken at
      baseline and at months 3 and 12. RESULTS: Pain: The severity of pain was
      decreased in patients treated with HA+L on application (P <.001) and 10 minutes
      later ( P=.008). Efficacy and satisfaction: No significant differences existed
      between the 2 groups at months 3, 9, and 12. RCM: Skin rejuvenation occurred with
      a 32% increase in the height of the dermoepidermal junction at month 12 (P
      <.001), which was similar in both groups. Adverse events: At month 3, the most
      common adverse events (AEs) were erythema (68%) and hematoma (11%). No AEs were
      recorded at months 9 or 12. CONCLUSION: The use of HA+L provides pain relief
      without affecting efficacy, satisfaction, safety, or the duration of results. RCM
      showed that the changes in the dermoepidermal junction represented a histological
      improvement in the skin with similar results in both groups.

PMID- 23545927
TI  - Assessment of syndecan-1 (CD138) and Ki-67 expression for differentiating
      keratoacanthoma and squamous cell carcinoma.
AB  - BACKGROUND: There is a major controversy over the natural behavior of
      keratoacanthoma (KA). KAs have been described as benign lesions, but also as
      variants of squamous cell carcinoma (SCC). Microscopic differentiation between
      these 2 entities is problematic, and sometimes impossible. Syndecan-1 (CD138) is
      an adhesion molecule whose expression appears to be inversely correlated with
      tumor invasiveness. Elevated Ki-67 expression is indicative of a high
      proliferation index, a feature of malignant tumors. METHODS: Syndecan-1 and Ki-67
      expression were assessed in 22 KA skin samples and in 17 SCC skin biopsies.
      RESULTS: Syndecan-1 expression was diminished in the SCC specimens compared with
      the KA specimens ( P =.000). Ki-67 expression was increased in the SCC specimens
      compared with the KA specimens, with mean values of 9 and 0.08, respectively ( P
      =.000). LIMITATIONS: Further studies that compare intermediate risk KAs to
      typical KAs and SCCs are required to corroborate these findings. CONCLUSION: The
      assessment of syndecan-1 and Ki-67 expression in skin biopsies is a helpful tool
      for differentiating KA and SCC

PMID- 23545928
TI  - Evaluation of a hydroquinone-free skin brightening product using in vitro
      inhibition of melanogenesis and clinical reduction of ultraviolet-induced
      hyperpigmentation.
AB  - BACKGROUND AND OBJECTIVE: Skin lightening preparations are used by people all
      over the world for a diverse range of dermatologic indications. Hydroquinone (HQ)
      is the gold standard and remains the only prescription product available in the
      United States for the treatment of generalized facial hyperpigmentation.
      Irritation and the risk of exogenous ochronosis are the main adverse effects for
      concern. Therefore, there has been a constant search for new treatment
      alternatives. Understanding the molecular mechanisms involved in pigmentation has
      resulted in the development of a series of formulations that utilize a multimodal
      treatment approach. These proprietary formulas combine skin lightening agents
      that act via different mechanisms of action. The actives included 4
      ethoxybenzaldehyde (anti-inflammatory and prostaglandin E2 suppressor), licorice
      extract (tyrosinase inhibitor), tetrahexyldecyl ascorbate (antioxidant),
      niacinamide (melanosome transport inhibitor), ethyl linoleate (tyrosinase
      inhibitor; enhances turnover of epidermis), hexylresorcinol (tyrosinase
      inhibitor), and retinol (tyrosinase transcription inhibitor; enhances turnover of
      epidermis). METHODS: Select formulations were tested in several studies using the
      MelanoDermTM Skin Model (MatTek Corporation, Ashland, MA) to assess the ability
      of the product to reduce melanin production and distribution. A single-center,
      double-blind comparison clinical study of 18 subjects was conducted to evaluate
      the efficacy of the product in reducing ultraviolet-induced hyperpigmentation.
      Test sites were irradiated with 1.0, 1.5, 2.0, and 2.5 minimal erythema doses.
      After 5 days, to allow for pigmentation development, the product or 4% HQ cream
      was applied to the respective test sites, once daily for 4 weeks. Chroma Meter
      measurements (L* brightness) and standardized digital photographs were taken of
      the test sites twice a week. RESULTS: The test product resulted in greater
      reduction in melanin as measured by melanin content and histological staining
      compared with the positive control in the MelanoDerm Skin Model. The product also
      demonstrated statistically significant reductions in pigmentation compared with
      baseline (all P <=.0001) at the end of the clinical study, and produced greater
      increases in L*, compared with 4% HQ. Results from these studies indicate that a
      product designed to affect multiple pathways of melanogenesis and melanin
      distribution may provide an additional treatment option beyond HQ for
      hyperpigmentation.

PMID- 23545929
TI  - Clinical efficacy and safety of a multimodality skin brightener composition
      compared with 4% hydroquinone.
AB  - There are numerous common skin disorders involving hyperpigmentation, including
      solar lentigines, postinflammatory hyperpigmentation, melasma, freckles, and
      dyschromia from photoaging. While these conditions are of an aesthetic nature,
      there is great interest in newer, safer, and more effective treatment modalities.
      Topical hydroquinone (HQ) has been the gold standard of skin lighteners for many
      years. However, regulatory authorities around the world are now questioning its
      safety. A randomized, double-blind, half-face study was conducted in females with
      moderate to severe facial hyperpigmentation to assess the efficacy and
      tolerability of 3 new skin brightener formulations containing SMA-432, a
      prostaglandin E2 inhibitor, compared with 4% HQ. Each subject was assigned 2 of
      the 4 test materials and was instructed to apply the product on the assigned side
      of the face twice daily for 12 weeks. Evaluation visits were conducted at
      baseline and at 4, 8, and 12 weeks. At each visit, subjects were evaluated by a
      blinded investigator for clinical efficacy and tolerability using grading scales.
      Standardized digital photography and Chroma Meter assessments were also taken.
      Self-assessment questionnaires were completed at weeks 4, 8, and 12. Sixty-eight
      Caucasian subjects (136 half faces) completed the study. All test materials
      significantly reduced Overall Hyperpigmentation and improved the Investigator's
      Global Hyperpigmentation Improvement rating at weeks 4, 8, and 12 compared with
      baseline. SMA-432 exhibited a dose-dependent improvement in hyperpigmentation.
      There were no major tolerability issues with any of the test materials. Self
      assessments were generally favorable for all test materials. At the completion of
      the trial, subjects rated one of the tested multimodality brightener compositions
      as the most favorable product and 4% HQ as the least favorable. This study
      demonstrated that the new non-HQ-containing skin brightener formulations were as
      effective and equally well tolerated as the gold standard, 4% HQ, in females with
      facial hyperpigmentation.

PMID- 23545930
TI  - Safety and efficacy of a novel multimodality hydroquinone-free skin brightener
      over six months.
AB  - BACKGROUND: Abnormal accumulation of melanin is a common aesthetic skin concern.
      For years, the gold standard for the treatment of hyperpigmentary disorders has
      been 4% hydroquinone (HQ). Due to regulatory agencies around the world
      questioning the safety of HQ, there has been interest in developing new HQ-free
      skin brightening/lightening products. A multimodality product (skin brightening
      complex) addressing various pathways for melanogenesis was developed as an
      alternative to HQ. OBJECTIVE: The skin brightening complex was studied for
      efficacy and tolerability in subjects with moderate to severe facial
      hyperpigmentation. METHODS: Subjects were instructed to apply skin brightening
      complex to the entire face twice daily and to follow a standard skin care regimen
      (facial cleanser, moisturizer, and sunscreen) during the course of the study. The
      study was conducted over a 12-week period and consisted of evaluation visits at
      baseline and at weeks 4, 8, and 12. At each visit, subjects were evaluated by an
      investigator for clinical efficacy and tolerability using grading scales.
      Standardized digital photographs and spectrophotometric assessments were also
      taken. Self-assessment questionnaires were completed at weeks 4, 8, and 12. To
      assess longer-term safety and efficacy, 10 subjects elected to continue treatment
      for an additional 12 weeks (24 weeks total), with evaluations at weeks 18 and 24.
      RESULTS: Twenty-six subjects completed the 12-week study, and 8 subjects
      completed treatment for an additional 12 weeks (24 weeks in total). In the 12
      week study, the skin brightening complex was shown to be effective and
      significantly improved Overall Hyperpigmentation at weeks 4, 8, and 12 compared
      with baseline. The skin brightening complex also significantly improved the
      Mottled Pigmentation Area and Severity Index ([MoPASI], a modified Melasma Area
      and Severity Index [MASI] scale) at weeks 8 and 12 compared with baseline. These
      efficacy benefits continued at 24 weeks. The product was well tolerated at all
      evaluation visits. Subject questionnaires showed 80% or more of the subjects
      reporting pigmentation improvement and satisfaction with the skin brightening
      complex at all evaluation visits. CONCLUSION: This HQ-free skin brightening
      complex was effective and well tolerated in subjects with facial
      hyperpigmentation who were treated for as long as 24 weeks.

PMID- 23545931
TI  - Comparative study of hydroquinone-free and hydroquinone-based hyperpigmentation
      regimens in treating facial hyperpigmentation and photoaging.
AB  - BACKGROUND: Photoaged skin, characterized by mottled, irregular areas of
      pigmentation, is a common skin condition that is often difficult to treat. The
      areas of hypermelanosis are an aesthetic concern to subjects and may lead to
      social distress and quality of life issues. There are many commercial
      hyperpigmentation regimens marketed to lighten dark spots and improve overall
      skin dyschromia. However, data to support efficacy of such kits are often
      lacking. OBJECTIVE: This investigator-blinded, randomized trial was conducted to
      compare a new hydroquinone (HQ)-free hyperpigmentation regimen against a leading
      HQ-based hyperpigmentation regimen for the treatment of facial hyperpigmentation
      and photoaging. METHODS: Subjects with mottled pigmentation and photodamaged
      facial skin were randomized to treatment with either the new 4-product (HQ-free)
      SkinMedica(r) Hyperpigmentation System (SKM; SkinMedica, an Allergan Company,
      Carlsbad, CA) kit or the 7-product (HQ-containing) Obagi Nu-Derm System (OMP;
      Obagi Medical Products, Long Beach, CA) kit. Subjects were evaluated by a blinded
      investigator for clinical efficacy and tolerability using grading scales at
      baseline and at weeks 4, 8, and 12. Standardized digital photographs were taken
      at baseline and week 12. Self-assessment questionnaires were completed at week
      12. RESULTS: Thirty-six female subjects (16: SKM; 20: OMP) completed the 12-week
      comparative study. Both hyperpigmentation regimens significantly reduced Overall
      Hyperpigmentation, Mottled Pigmentation Area and Severity Index (MoPASI), global
      photoaging, and sallowness at week 12 compared to baseline. Significant
      reductions in tactile roughness were seen with the OMP regimen at week 12. In
      these investigator-blinded assessments, there were no significant differences
      between treatment groups, nor was there a difference in global response to
      treatment. Investigator assessments of tolerability showed mean scores were mild
      or below for all parameters with both treatment regimens. CONCLUSION: A new 4
      product (HQ-free) regimen was shown to be as effective and tolerable as a 7
      product (HQ-based) regimen in reducing facial hyperpigmentation and photoaging in
      females with mottled pigmentation and photodamaged facial skin.

PMID- 23545933
TI  - Hydroquinone-free multimodal topical regimen for facial hyperpigmentation.
AB  - To assess the treatment of hyperpigmentation, a series of 5 case studies were
      conducted to evaluate the efficacy and tolerability of a novel hydroquinone-free
      treatment regimen combining a multimodal skin brightener with a cleanser, high
      strength retinol product and sunscreen SPF 30+. Patients presented with moderate
      to severe facial hyperpigmentation as determined by a score of 4 to 8 on the
      Overall Hyperpigmentation scale. Physician-graded Overall Hyperpigmentation,
      Global Improvement in Hyperpigmentation, and standardized photography were
      conducted at weeks 3, 6, and 12. At week 12, the majority of patients
      demonstrated Global Improvements in Hyperpigmentation of at least 50%, with at
      least a 2-grade reduction in Overall Hyperpigmentation scores, as assessed by the
      physician. Standardized photographs also support the physician and patient
      findings. Results from these case studies demonstrate that this unique 12-week
      treatment regimen can provide an effective and simple option for patients with
      facial hyperpigmentation.

PMID- 23545932
TI  - Assessment of a superficial chemical peel combined with a multimodal,
      hydroquinone-free skin brightener using in vivo reflectance confocal microscopy.
AB  - The combination of in-office procedures such as chemical peels with topical
      maintenance therapies has been shown to provide greater efficacy than either
      treatment by itself in the management of melasma. A series of 3 case studies were
      conducted to evaluate the efficacy and tolerability of one superficial chemical
      peel (containing a proprietary blend of resorcinol, lactic acid, salicylic acid,
      and retinol) combined with a topical multimodal, hydroquinone-free skin
      brightener as postpeel maintenance therapy. Patients presented with moderate to
      severe facial hyperpigmentation. At baseline, subjects received the superficial
      chemical peel treatment followed by a standard postpeel skin care regimen
      (cleanser, moisturizer, and SPF 30+ sunscreen). Approximately 1 week after the
      peel procedure, subjects initiated twice-daily application of the skin
      brightener. Subjects were then evaluated for Global Improvement in
      Hyperpigmentation by the investigator for up to 7 weeks postpeel. Standardized
      digital photographs of the subjects facial skin and in vivo reflectance confocal
      microscopy (RCM) images were taken of a target hyperpigmented lesion at baseline
      and at follow-up. Standardized photography and in vivo RCM images at baseline and
      at postpeel show the improvements observed by the investigator. Results from
      these case studies suggest that the combination of a superficial chemical peel
      with topical maintenance and the multimodal skin brightener may provide an
      effective treatment approach for subjects with moderate to severe facial
      hyperpigmentation.

PMID- 23545934
TI  - The only topical retinoid without a generic alternative: tazarotene.

PMID- 23545935
TI  - A status report on topical tazarotene in the management of acne vulgaris.
AB  - Tazarotene is a synthetic retinoid that, depending on the concentration and
      vehicle, is approved by the US Food and Drug Administration for the topical
      treatment of acne vulgaris (AV) and plaque psoriasis. Tazarotene is also used as
      adjunctive treatment for specified clinical manifestations of chronically
      photodamaged skin (facial fine wrinkling, mottled facial hypopigmentation and
      hyperpigmentation, and benign facial lentigines), along with comprehensive skin
      care and photoprotection from sunlight. The gel formulation was released in the
      United States in 1997, with the cream formulation made available in 2000.
      Multiple studies are available supporting the effective and safe use of topical
      tazarotene for each of its indications. This article provides an overview of the
      pharmacology of topically applied tazarotene, discussing in particular up-to-date
      information on the efficacy, tolerability, and safety of topical tazarotene for
      AV, including monotherapy and combination therapy studies. Topical tazarotene
      0.1% in both formulations is highly effective in reducing both inflammatory and
      noninflammatory acne lesions, and can be used in combination with other topical
      agents, including formulations containing benzoyl peroxide or dapsone 5% gel.
      Although many patients tolerate the use of topical tazarotene without significant
      issues or concerns, some patients experience application-site tolerability
      reactions, which can usually be managed with proper skin care and are less
      frequent with the cream formulation.

PMID- 23545937
TI  - Extracellular calcium-sensing receptor/PTH knockout mice colons have increased
      Wnt/beta-catenin signaling, reduced non-canonical Wnt signaling, and increased
      susceptibility to azoxymethane-induced aberrant crypt foci.
AB  - Epidemiological evidence suggests increased dietary calcium and dairy products
      reduce the onset of colon cancer. To understand a role of the colonic
      extracellular calcium-sensing receptor (CaSR) in calcium-mediated chemoprevention
      of colon cancer, we induced formation of aberrant crypt foci (ACF) caused by
      azoxymethane (AOM) injection in 'rescued' CaSR-/PTH- (C-/P-) double knockout
      colons compared with colons from control CaSR+/PTH+ (C+/P+) mice. C-/P- colonic
      epithelia had increased Wnt/beta-catenin signaling as evidenced by 3-8-fold
      increases in Wnt3a, CyclinD1, and MMP-7 proteins compared with C+/P+ colonic
      epithelia. The C-/P- colonic epithelia had reduced Wnt5a and Ror2, and a three
      fold increase in TNFR1 compared with C+/P+ epithelia. The C-/P- colons and small
      intestine had extensive neutrophil infiltration with myeloperoxidase (MPO) levels
      18-fold higher then C+/P+ small intestine and colon. Saline-injected C-/P- colons
      had the same number of ACF/cm(2) as C+/P+ colons, which were injected with AOM.
      However, there were eight times more ACF/cm(2) in the C-/P- injected with AOM
      compared with C+/P+ colons, which received AOM. Together our results suggest both
      inflammation and Wnt/beta-catenin signaling are increased in the epithelia of
      'rescued' CaSR/PTH double knockout colons, and the capacity for non-canonical Wnt
      signaling through Wnt5a/Ror2 engagement is reduced. The loss of the colonic CaSR
      increased the number of ACF/cm(2) in response to AOM injection, suggesting
      colonic CaSR may mediate the chemoprotective effect of increased dietary calcium
      against colorectal cancer observed in humans.

PMID- 23545936
TI  - Newer antipsychotics and upcoming molecules for schizophrenia.
AB  - BACKGROUND: The management of schizophrenia has seen significant strides over the
      last few decades, due to the increasing availability of a number of
      antipsychotics. Yet, the diminished efficacy in relation to the negative and
      cognitive symptoms of schizophrenia, and the disturbing adverse reactions
      associated with the current antipsychotics, reflect the need for better molecules
      targeting unexplored pathways. PURPOSE: To review the salient features of the
      recently approved antipsychotics; namely, iloperidone, asenapine, lurasidone and
      blonanserin. METHODS: We discuss the advantages, limitations and place in modern
      pharmacotherapy of each of these drugs. In addition, we briefly highlight the new
      targets that are being explored. RESULTS: Promising strategies include modulation
      of the glutamatergic and GABAergic pathways, as well as cholinergic systems.
      CONCLUSIONS: Although regulatory bodies have approved only a handful of
      antipsychotics in recent years, the wide spectrum of targets that are being
      explored could eventually bring out antipsychotics with improved efficacy and
      acceptability, as well as the potential to revolutionize psychiatric practice.

PMID- 23545938
TI  - RIP1 expression is necessary for CD30-mediated cell death induction in anaplastic
      large-cell lymphoma cells.
AB  - CD30, a member of the tumor necrosis factor receptor (TNFR) superfamily, is
      consistently expressed by tumor cells of anaplastic large-cell lymphoma (ALCL).
      CD30 stimulation induces massive caspase-dependent cell death of ALCL cells in
      case of canonical NFkappaB inhibition or proteasome inhibition. However, CD30, a
      TNFR lacking a death domain (DD), is unable to recruit a death inducing complex
      containing TRADD (TNFR1-associated DD-protein) or FADD (FAS-associated DD-domain
      protein) together with the receptor-interacting protein 1 (RIP1) and caspase-8.
      Thus, the mechanism explaining CD30-induced cell death of lymphocytes remains
      obscure. Here, we demonstrate that blockage of RIP1 by siRNA or pharmacological
      inhibition of RIP1 by Necrostatin-1 almost completely prevented CD30-induced cell
      death. In addition, we revealed CD30-induced accumulation of RIP1 at the
      cytoplasma membrane of NFkappaB-inhibited ALCL cells by confocal laser scanning
      microscopy. Finally, primary ALCL cases can be subdivided into two groups based
      on the presence or absence of RIP1 as revealed by immunohistology. Taken
      together, our study identified RIP1 as a crucial mediator of CD30-induced cell
      death that bears features of apoptosis as well as necroptosis. RIP1 expression in
      ALCL tumor cells might eligible for the therapeutic application of CD30
      antibodies in combination with NFkappaB/proteasome inhibitors that should result
      in CD30-induced cell death.

PMID- 23545939
TI  - Demand of words.

PMID- 23545940
TI  - Effects of matrine on oval cell-mediated liver regeneration and expression of RBP
      Jkappa and HES1.
AB  - In the present study a rat model of oval cell-mediated liver regeneration was
      constructed to examine the molecular mechanisms of matrine in oval cell-mediated
      liver regeneration and the effects of matrine on hepatic function and the
      expression of OV6 protein and recombination signal sequence-binding protein
      Jkappa (RBP-Jkappa) and HES1 mRNA. A total of 48 Sprague Dawley rats were equally
      and randomly assigned to two groups. The model group underwent oval cell-mediated
      liver regeneration, whereas the matrine group underwent oval cell-mediated liver
      regeneration and received oral gavage of matrine. Expression of OV6 protein was
      tested by immunohistochemistry and RBP-Jkappa and HES1 mRNA expression was
      determined by reverse-transcription polymerase chain reaction. Recovery of
      hepatic function was faster in the matrine group compared with the model
      (P<0.05). OV6 protein, RBP-Jkappa and HES1 mRNA expression levels were lower in
      the matrine than the model group (P<0.05). Matrine promotes oval cell-mediated
      liver regeneration through downregulation of the RBP-Jkappa-HES1 signaling
      pathway.

PMID- 23545942
TI  - A proteomics approach to study the molecular basis of enhanced salt tolerance in
      barley (Hordeum vulgare L.) conferred by the root mutualistic fungus
      Piriformospora indica.
AB  - Piriformospora indica is a root-interacting mutualistic fungus capable of
      enhancing plant growth, increasing plant resistance to a wide variety of
      pathogens, and improving plant stress tolerance under extreme environmental
      conditions. Understanding the molecular mechanisms by which P. indica can improve
      plant tolerance to stresses will pave the way to identifying the major mechanisms
      underlying plant adaptability to environmental stresses. We conducted greenhouse
      experiments at three different salt levels (0, 100 and 300 mM NaCl) on barley
      (Hordeum vulgare L.) cultivar "Pallas" inoculated with P. indica. Based on the
      analysis of variance, P. indica had a significant impact on the barley growth and
      shoot biomass under normal and salt stress conditions. P. indica modulated ion
      accumulation in colonized plants by increasing the foliar potassium (K(+))/sodium
      (Na(+)) ratio, as it is considered a reliable indicator of salt stress tolerance.
      P. indica induced calcium (Ca(2+)) accumulation and likely influenced the stress
      signal transduction. Subsequently, proteomic analysis of the barley leaf sheath
      using two-dimensional electrophoresis resulted in detection of 968 protein spots.
      Of these detected spots, the abundance of 72 protein spots changed significantly
      in response to salt treatment and P. indica-root colonization. Mass spectrometry
      analysis of responsive proteins led to the identification of 51 proteins. These
      proteins belonged to different functional categories including photosynthesis,
      cell antioxidant defense, protein translation and degradation, energy production,
      signal transduction and cell wall arrangement. Our results showed that P. indica
      induced a systemic response to salt stress by altering the physiological and
      proteome responses of the plant host.

PMID- 23545943
TI  - Remarkable fluorescence change based on the protonation-deprotonation control in
      organic crystals.
AB  - Insights into the origin of the fluorescence responsive to protonation
      deprotonation stimuli were provided through the study on the crystals of a new
      stimuli-responsive molecule BP3VA. And the transformation between microcrystals
      demonstrated the varying emissions of the BP3VA powder.

PMID- 23545941
TI  - The "DGPPN-Cohort": A national collaboration initiative by the German Association
      for Psychiatry and Psychotherapy (DGPPN) for establishing a large-scale cohort of
      psychiatric patients.
AB  - The German Association for Psychiatry and Psychotherapy (DGPPN) has committed
      itself to establish a prospective national cohort of patients with major
      psychiatric disorders, the so-called DGPPN-Cohort. This project will enable the
      scientific exploitation of high-quality data and biomaterial from psychiatric
      patients for research. It will be set up using harmonised data sets and
      procedures for sample generation and guided by transparent rules for data access
      and data sharing regarding the central research database. While the main focus
      lies on biological research, it will be open to all kinds of scientific
      investigations, including epidemiological, clinical or health-service research.

PMID- 23545944
TI  - Prognostic value of CAPZA1 overexpression in gastric cancer.
AB  - F-actin capping protein alpha1 subunit (CAPZA1) was previously identified in a
      proteomic analysis of human gastric cancer clinical specimens and selected for
      further study. The association between CAPZA1 overexpression, detected by
      immunohistochemistry, and clinicopathological features including survival were
      evaluated. In vitro gain-of-function and loss-of-function approaches were
      utilized to assess the function of CPAZA1 in malignancy. Univariate analysis
      revealed that poorly differentiated disease, according to the World Health
      Organization (WHO) classification, advanced T stage, positive lymph nodes, high
      TNM stage, D2 lymph node dissection, adjuvant chemotherapy and CAPZA1
      underexpression were significantly associated with cancer-related death (p<0.05);
      however, only high TNM stage remained significantly associated by multivariate
      analysis (p<0.01). CAPZA1 overexpression was associated with well differentiated
      histology, smaller tumor size, lower T stage, absence of lymph node metastasis,
      lower TNM stage, lower recurrence rate and longer survival time, compared to
      CAPZA1 underexpression. In vitro, forced expression of CAPZA1 caused a
      significant decrease in gastric cancer cell migration and invasion, whereas
      CAPZA1 depletion had the opposite effect. The present study suggests that CAPZA1
      could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is
      associated with decreased cancer cell migration and invasion.

PMID- 23545946
TI  - Expert opinion: why is MRI still an under-utilized modality for evaluating
      thoracic disorders?

PMID- 23545945
TI  - Angiotensin-converting enzyme 2 attenuates the metastasis of non-small cell lung
      cancer through inhibition of epithelial-mesenchymal transition.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin
      system (RAS). ACE2 plays a critical counterbalancing role by degrading
      angiotensin II (Ang II) to Ang 1-7. Recent studies suggest that RAS influences
      tumor growth and development by its paracrine effects on the tumor
      microenvironment. Epithelial-mesenchymal transition (EMT) is now thought to be a
      process that plays a fundamental role in tumor progression and metastasis. In the
      present study, we investigated the role of ACE2 in lung cancer metastasis and the
      mechanism of EMT. This is the first study to elucidate the mechanism through
      which the overexpression of ACE2 in the A549 lung cancer cell line decreases
      metastasis formation in vivo and upregulates the expression of E-cadherin both in
      vitro and in vivo. We also observed the downregulation of vimentin, which
      supports a role of ACE2 in influencing EMT in lung cancer. Further analysis
      indicated that ACE2 abrogated the upregulation of TGF-beta1-induced EMT markers,
      such as vimentin and alpha-smooth muscle actin (alphaSMA) in vitro in A549 cells.
      Finally, exposing A549 cells stably expressing ACE2 to DX600, an inhibitor of
      ACE2, recovered the sensitivity of lung cancer cells to TGF-beta1-mediated
      induction of EMT. Our study demonstrated that ACE2 attenuated the metastasis of
      lung cancer and may serve as a target for new strategies to inhibit EMT in cancer
      cells.

PMID- 23545947
TI  - Thoracic magnetic resonance imaging for the evaluation of pulmonary emphysema.
AB  - Pulmonary emphysema is a pathologic condition characterized by permanently
      enlarged airspaces distal to the terminal bronchiole with destruction of the
      alveolar walls. Functional information of the lungs is important to understand
      the pathophysiology of emphysema and that of chronic obstructive pulmonary
      disease. With the recent developments in magnetic resonance imaging (MRI)
      techniques, functional MRI with variable MR sequences can be used for the
      evaluation of different physiological and anatomic changes seen in cases of
      pulmonary emphysema. In this review article, we will focus on a brief description
      of each method, results of some of the most recent work, and the clinical
      application of such knowledge.

PMID- 23545948
TI  - Magnetic resonance imaging of cystic fibrosis lung disease.
AB  - Lung involvement in cystic fibrosis (CF) disease continues to be a major life
      limiting factor of this autosomal recessive genetic disorder. Efforts made toward
      early diagnosis and advances in therapy have led to sustained survival of
      affected patients, and many are now of adult age. Because imaging provides
      detailed information on regional distribution of CF lung disease, repetitive
      imaging is required for severity assessment and therapy monitoring not only in
      clinical routine but also for interventional trials. Computed tomography has long
      succeeded chest radiograph because it provides the highest morphologic detail of
      airway and parenchymal changes. This is inseparably accompanied by an increase in
      radiation exposure to CF individuals, who are critically susceptible to, and may
      accumulate, relevant doses during their lifetime. Magnetic resonance imaging
      (MRI) as an ionizing radiation-free cross-sectional imaging modality is capable
      of depicting anatomic hallmarks of CF lung disease at lower spatial resolution
      but with enhanced tissue characterization. Comprehensive functional lung imaging
      (imaging of respiratory mechanics, ventilation, and lung perfusion) provides
      valuable additional information that cannot or can hardly be obtained by any
      other single diagnostic procedure. The present review article strives to present
      the current state of lung MRI in CF, as well as its future perspectives.
      Functional MRI of the CF lung is at the threshold of being considered a routine
      application, which, supporting early diagnosis, may help to further improve the
      survival of CF patients.

PMID- 23545949
TI  - Thoracic magnetic resonance imaging: pulmonary thromboembolism.
AB  - Ongoing technical developments have substantially improved the potential of
      magnetic resonance imaging (MRI) in the assessment of the pulmonary circulation.
      These developments includes improved magnet and hardware design, new k-space
      sampling techniques (ie, parallel imaging), and alternative contrast materials.
      With these techniques, not only can pulmonary vessels be visualized by MR
      angiography with high spatial resolution but also the perfusion of the lungs and
      its changes in relation to pulmonary thromboembolism (PE) can be assessed.
      Considering venous thromboembolism as a systemic disease, MR venography might be
      added for the diagnosis of underlying deep venous thrombosis. A unique advantage
      of MRI over other imaging tests is its potential to evaluate changes in cardiac
      function as a result of obstruction of the pulmonary circulation, which may have
      a significant impact on patient monitoring and treatment. Finally, MRI does not
      involve radiation, which is advantageous, especially in young patients. Over the
      years, a number of studies have shown promising results not only for MR
      angiography but also for MRI of lung perfusion and for MR venography. This review
      article summarizes and discusses the current evidence on pulmonary MRI for
      patients with suspected PE.

PMID- 23545950
TI  - Workplace antistigma initiatives: a scoping study.
AB  - OBJECTIVE: The purpose of this scoping study was to identify and describe the
      principles and characteristics embedded in workplace mental health antistigma
      initiatives. Research in this area is diffuse and not well synthesized.
      Therefore, a scoping study is useful in generating a breadth of coverage and
      identifying all relevant literature on the topic regardless of study design.
      Results will inform evaluation strategies and can be used to distinguish the
      effectiveness of particular elements in future research. METHODS: The "York
      Framework," a five-stage methodological design (with an optional sixth stage) was
      used as the structure for this study. Eleven peer-reviewed and gray-literature
      databases were searched (2000-2011), and an extensive Internet review was also
      conducted. Two reviewers independently reviewed all abstracts to determine study
      selection. A data chart consisting of key issues and themes was utilized to
      extract data from the included studies. Preliminary results were used to inform a
      stakeholder consultation with seven international experts. RESULTS: Twenty-two
      antistigma interventions were included in the study. Most of the initiatives have
      appeared in the past four years and across geographic boundaries, reflecting the
      growing international interest in mental health in the workplace. A large
      proportion of the interventions utilize educational approaches to reducing
      stigma, and a substantial number target military personnel. CONCLUSIONS: Stronger
      evidence for effective practices needs to be established through the use of
      standardized workplace-specific interventions, reliable and valid evaluation
      tools, and overall enhanced scientific rigor.

PMID- 23545951
TI  - Transformation of potassium Lindquist hexaniobate to various potassium niobates:
      solvothermal synthesis and structural evolution mechanism.
AB  - This paper introduces the formation reactions and reaction mechanisms of a series
      of potassium niobates from a potassium salt of the Lindquist hexaniobate
      [Nb6O19](8-) ion under solvothermal conditions. The structure and particle
      morphology of the potassium niobate product can be controlled easily with the
      reaction solution alkalinity using this solvothermal process. KNb3O8 with a plate
      like morphology, K4Nb6O17.4.5H2O with a plate-like morphology, a new phase of
      K2Nb2O6.H2O with fibrous morphology, KNbO3 perovskites with cubic morphology are
      obtained at pH = 5.5, and in 0.3, 0.5, 1.0 mol L(-1) KOH solutions at 230 
      degrees C, respectively. The reaction conditions are much milder than those in
      the normal hydrothermal process. Furthermore, the K2Nb2O6.H2O fibers can be
      topotactically transformed into KNbO3 fibers, Nb2O5 fibers after H(+)-exchange
      treatment, and LiNbO3 fibers after Li(+)-exchange-treatment by heat-treatments at
      730, 560, and 520  degrees C, respectively. The formation reaction and structure
      of these potassium niobates were characterized by X-ray diffraction (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      selected-area electron diffraction (SAED), energy-dispersive spectroscopy (EDS),
      Raman spectra and TG-DTA. The formation mechanism of this series of potassium
      niobates from the [Nb6O19](8-) precursor is systematically explained via the
      correlation between the octahedrons [NbO6] sharing forms in the precursor
      structure and in the product structures.

PMID- 23545953
TI  - Characterization of surface modified ZnCuInS2 nanocrystals and its application to
      white light-emitting diodes.
AB  - Red-emitting ZnCuInS2 semiconductor nanocrystals (NCs) were synthesized and
      surface modification was performed on the NCs with oleylamine, trioctylphosphine,
      and 3-mercaptopropionic acid by the ligand exchange strategy. UV-visible
      spectroscopy, photoluminescence (PL) spectroscopy, time-resolved PL analysis, and
      attenuated total reflection Fourier transform infrared spectroscopy were used to
      verify the surface modification of NCs. Additionally, white light-emitting diodes
      (LEDs) were fabricated using surface modified red-emitting ZnCuInS2 NCs as red
      phosphor to compensate for the deficiency of red emission in white LEDs,
      consisting of blue LEDs as excitation sources and YAG:Ce as yellow phosphor.

PMID- 23545954
TI  - Thin-film thickness profile measurement by three-wavelength interference color
      analysis.
AB  - Conventional transparent film thickness measurement methods such as spectroscopy
      are essentially capable of measuring only a single point at a time, and their
      spatial resolution is limited. We propose a film thickness measurement method
      that is an extension of the global model-fitting algorithm developed for three
      wavelength interferometric surface profiling. It estimates the film thickness
      distribution from an interference color image captured by a color camera with
      three-wavelength illumination. The proposed method is validated through computer
      simulations and experiments.

PMID- 23545955
TI  - Maximum-likelihood estimation for frequency-modulated continuous-wave laser
      ranging using photon-counting detectors.
AB  - We analyze the minimum achievable mean-square error in frequency-modulated
      continuous-wave range estimation of a single stationary target when photon
      counting detectors are employed. Starting from the probability density function
      for the photon-arrival times in photodetectors with subunity quantum efficiency,
      dark counts, and dead time, we derive the Cramer-Rao bound and highlight three
      important asymptotic regimes. We then derive the maximum-likelihood (ML)
      estimator for arbitrary frequency modulation. Simulation of the ML estimator
      shows that its performance approaches the standard quantum limit only when the
      mean received photons are between two thresholds. We provide analytic
      approximations to these thresholds for linear frequency modulation. We also
      compare the ML estimator's performance to conventional Fourier transform (FT)
      frequency estimation, showing that they are equivalent if the reference arm is
      much stronger than the target return, but that when the reference field is weak
      the FT estimator is suboptimal by approximately a factor of ?2 in root-mean
      square error. Finally, we report on a proof-of-concept experiment in which the ML
      estimator achieves this theoretically predicted improvement over the FT
      estimator.

PMID- 23545956
TI  - Generalized ocean color inversion model for retrieving marine inherent optical
      properties.
AB  - Ocean color measured from satellites provides daily, global estimates of marine
      inherent optical properties (IOPs). Semi-analytical algorithms (SAAs) provide one
      mechanism for inverting the color of the water observed by the satellite into
      IOPs. While numerous SAAs exist, most are similarly constructed and few are
      appropriately parameterized for all water masses for all seasons. To initiate
      community-wide discussion of these limitations, NASA organized two workshops that
      deconstructed SAAs to identify similarities and uniqueness and to progress toward
      consensus on a unified SAA. This effort resulted in the development of the
      generalized IOP (GIOP) model software that allows for the construction of
      different SAAs at runtime by selection from an assortment of model
      parameterizations. As such, GIOP permits isolation and evaluation of specific
      modeling assumptions, construction of SAAs, development of regionally tuned SAAs,
      and execution of ensemble inversion modeling. Working groups associated with the
      workshops proposed a preliminary default configuration for GIOP (GIOP-DC), with
      alternative model parameterizations and features defined for subsequent
      evaluation. In this paper, we: (1) describe the theoretical basis of GIOP; (2)
      present GIOP-DC and verify its comparable performance to other popular SAAs using
      both in situ and synthetic data sets; and, (3) quantify the sensitivities of
      their output to their parameterization. We use the latter to develop a
      hierarchical sensitivity of SAAs to various model parameterizations, to identify
      components of SAAs that merit focus in future research, and to provide material
      for discussion on algorithm uncertainties and future emsemble applications.

PMID- 23545957
TI  - High-temperature sensor based on an abrupt-taper Michelson interferometer in
      single-mode fiber.
AB  - This study proposes a high-temperature sensor based on an abrupt fiber-taper
      Michelson interferometer (FTMI) in single-mode fiber fabricated by a fiber-taper
      machine and electric-arc discharge. The proposed FTMI is applied to measure
      temperature and refractive index (RI). A high temperature sensitivity of 118.6
      pm/ degrees C is obtained in the temperature range of 500 degrees C-800 degrees
      C. The wavelength variation is only -0.335 nm for the maximum attenuation peak,
      with the external RI changed from 1.333 to 1.3902, which is desirable for high
      temperature sensing to eliminate the cross sensitivity to RI.

PMID- 23545958
TI  - Absolute distance measurement using frequency-sweeping heterodyne interferometer
      calibrated by an optical frequency comb.
AB  - We present a frequency-sweeping heterodyne interferometer to measure an absolute
      distance based on a frequency-tunable diode laser calibrated by an optical
      frequency comb (OFC) and an interferometric phase measurement system. The laser
      frequency-sweeping process is calibrated by the OFC within a range of 200 GHz and
      an accuracy of 1.3 kHz, which brings about a precise temporal synthetic
      wavelength of 1.499 mm. The interferometric phase measurement system consisting
      of the analog signal processing circuit and the digital phase meter achieves a
      phase difference resolution better than 0.1 deg. As the laser frequency is
      sweeping, the absolute distance can be determined by measuring the phase
      difference variation of the interference signals. In the laboratory condition,
      our experimental scheme realizes micrometer accuracy over meter distance.

PMID- 23545959
TI  - Efficient generation of broad Raman sidebands in an index-guided photonic crystal
      fiber.
AB  - The efficient generation of broad Raman sidebands is experimentally demonstrated
      in a short piece of index-guided photonic crystal fiber, which is pumped by a
      high-peak-power pulse near the zero-dispersion wavelength and seeded by a
      continuous-wave Stokes signal centered at 1117 nm. The Raman sidebands generated
      via stimulated Raman scattering and cascaded four-wave mixing contain five Stokes
      and six anti-Stokes peaks and span from 827 to 1398 nm, and the 3 dB linewidth
      for each peak is smaller than 1 nm. However, the pure Raman sidebands are largely
      dependent on the pulse pump power as well as the fiber length.

PMID- 23545960
TI  - Analysis of optical damage in germanium induced by a continuous wave laser.
AB  - To analyze optical damage of germanium (Ge) induced by a continuous wave (CW)
      laser, numerical and experimental studies were carried out. Temperature and solid
      liquid phase transition with laser conditions were estimated by numerical
      simulation. In our experiments, we examined morphological changes with hillocks,
      material changes in the GeO2 layer by oxidation, and new crystal domains formed
      by recrystallization. The material damage process was explained. Transmittance
      reduction was also observed in the mid-infrared region. We confirmed that hillock
      formation, oxidation, and recrystallization through resolidification are critical
      factors in damaging the optical performance of Ge with a CW laser.

PMID- 23545961
TI  - Imaging characteristics of Zernike and annular polynomial aberrations.
AB  - The general equations for the point-spread function (PSF) and optical transfer
      function (OTF) are given for any pupil shape, and they are applied to optical
      imaging systems with circular and annular pupils. The symmetry properties of the
      PSF, the real and imaginary parts of the OTF, and the modulation transfer
      function (MTF) of a system with a circular pupil aberrated by a Zernike circle
      polynomial aberration are derived. The interferograms and PSFs are illustrated
      for some typical polynomial aberrations with a sigma value of one wave, and 3D
      PSFs and MTFs are shown for 0.1 wave. The Strehl ratio is also calculated for
      polynomial aberrations with a sigma value of 0.1 wave, and shown to be well
      estimated from the sigma value. The numerical results are compared with the
      corresponding results in the literature. Because of the same angular dependence
      of the corresponding annular and circle polynomial aberrations, the symmetry
      properties of systems with annular pupils aberrated by an annular polynomial
      aberration are the same as those for a circular pupil aberrated by a
      corresponding circle polynomial aberration. They are also illustrated with
      numerical examples.

PMID- 23545962
TI  - Color deviation controlling of phosphor conformal coating by advanced spray
      painting technology for white LEDs.
AB  - An advanced phosphor conformal coating technology is proposed, good correlated
      color temperature (CCT) and chromaticity uniformity samples are fabricated
      through phosphor spray painting technology. Spray painting technology is also
      suitable for phosphor conformal coating of whole LED wafers. The samples of
      different CCTs are obtained through controlling the phosphor film thickness in
      the range of 6-80 MUm; CCT variation of samples can be controlled in the range of
      +/-200 K. The experimental Deltauv reveals that the spray painting method can
      obtain a much smaller CCT variation (Deltauv of 1.36e(-3)) than the conventional
      dispensing method (Deltauv of 11.86e(-3)) when the light is emitted at angles
      from -90 degrees  to +90 degrees , and chromaticity area uniformity is also
      improved significantly.

PMID- 23545963
TI  - Regeneration of fiber Bragg gratings under strain.
AB  - The effect of strain on both the index modulation, Deltan(mod), and average
      index, Deltan, during grating regeneration within two types of fibers is studied.
      Significant tunability of the Bragg wavelength (lambda(B)>48 nm) is observed
      during postannealing at or above the strain temperature of the glass. The main
      reason for the grating wavelength shift during annealing with load is the
      elongation of the fiber. As well, the observed Moire interference cycling through
      regeneration indicates the presence of two gratings.

PMID- 23545964
TI  - Polarization-based refractive index sensor using dual asymmetric long-period
      gratings in ridge waveguides.
AB  - We propose a sensor scheme operating in the wavelength band of 1460-1530 nm (S
      band) that utilizes two orthogonally polarized eigenmodes in a ridge-waveguide
      geometry by employing a pair of nonidentical asymmetric long-period gratings.
      Numerical simulations show a high sensitivity ~4900 nm/RIU (refractive index
      unit) over the refractive index range 1.33-1.34 exhibiting a relative resonance
      shift of 1 pm for an index change of ~10(-7). Such high resolution sensors enable
      detection of minute changes with potential applications to various biochemical
      industries.

PMID- 23545965
TI  - Exciting higher-order radial Laguerre-Gaussian modes in a diode-pumped solid
      state laser resonator.
AB  - In this paper we experimentally demonstrate the intracavity generation of
      selected Laguerre-Gaussian modes of variable radial order, from 0 to 5. Our
      technique requires only an amplitude mask made up of absorbing rings to be placed
      inside the cavity, with the ring radii selected to coincide with the zeros of the
      desired Laguerre-Gaussian mode. We demonstrate high mode purity and a mode volume
      proportional to the order of the mode. Our results suggest a possible route to
      high brightness diode-pumped solid-state laser sources.

PMID- 23545966
TI  - Postanalyses of an optical multilayer interference filter using numerical reverse
      synthesis and Rutherford backscattering spectrometry.
AB  - Post nondestructive analyses of an all-dielectric multilayer Fabry-Perot
      interference filter developed through a reactive electron beam deposition process
      have been carried out through numerical reverse engineering of transmission
      spectra, Rutherford backscattering spectroscopy and quartz crystal monitoring
      data to derive multilayer geometry, deposited layer thicknesses, densities,
      refractive indices, compositions, and stoichiometry. These techniques are
      collectively used to fulfill the missing links with complementary and some
      supplementary information to inverse synthesize the multilayer geometry. During
      this investigation it is distinctly understood that the factors associated with
      real-time deposition have significantly influenced the microscopic parameters,
      namely, the densities and refractive indices of TiO2 and SiO2 layers. This in
      turn influenced the layers' geometric (physical) thicknesses during automated
      quarter-wave optical layer monitoring and consequently affected the experimental
      spectral characteristics. The role of oxygen has been observed to be significant
      in controlling the mass densities of these refractory oxide layers. It is further
      noticed that the layer density values have been significantly perturbed whether
      the associated TiO2 or SiO2 oxide dielectric films are substoichiometric (oxygen
      deficient), stoichiometric, or superstoichiometric (oxygen-enriched).

PMID- 23545967
TI  - Investigation of basal cell carcinoma using dynamic focus optical coherence
      tomography.
AB  - Optical coherence tomography (OCT) is becoming a popular modality for skin tumor
      diagnosis and assessment of tumor size and margin status. We conducted a number
      of imaging experiments on periocular basal cell carcinoma (BCC) specimens using
      an OCT configuration. This configuration employs a dynamic focus (DF) procedure
      where the coherence gate moves synchronously with the peak of the confocal gate,
      which ensures better signal strength and preservation of transversal resolution
      from all depths. A DF-OCT configuration is used to illustrate morphological
      differences between the BCC and its surrounding healthy skin in OCT images. The
      OCT images are correlated with the corresponding histology images. To the best of
      our knowledge, this is the first paper to look at DF-OCT imaging in examining
      periocular BCC.

PMID- 23545968
TI  - Cooled infrared filters and dichroics for the sea and land surface temperature
      radiometer.
AB  - The sea and land surface temperature radiometer (SLSTR) is a nine-channel visible
      and infrared high-precision radiometer designed to provide climate data of global
      sea and land surface temperatures. The SLSTR payload is destined to fly on the
      Ocean and Medium-Resolution Land Mission for the ESA/EU global monitoring for
      environment and security (GMES) programme Sentinel-3 mission to measure the sea
      and land temperature and topography for near real-time environmental and
      atmospheric climate monitoring of the Earth. In this paper we describe the
      optical layout of infrared optics in the instrument, the spectral thin-film
      multilayer design, and the system channel throughput analysis for the combined
      interference filter and dichroic beam splitter coatings to discriminate
      wavelengths at 3.74, 10.85, 12.0 MUm. The rationale for selection of thin-film
      materials, the deposition technique, and environmental testing, inclusive of
      humidity, thermal cycling, and ionizing radiation testing are also described.

PMID- 23545969
TI  - Algebraic and numerical analysis of imaging properties of thin tunable-focus
      fluidic membrane lenses with parabolic surfaces.
AB  - The theory of third-order aberrations for a system of rotationally symmetric thin
      tunable-focus fluidic membrane lenses with parabolic surfaces is described. A
      complex analysis of the third-order design of tunable fluidic lenses is performed
      considering all types of primary aberrations. Moreover, formulas are derived for
      the calculation of the change of aberration coefficients of the parabolic tunable
      fluidic membrane lens with respect to the wavelength. It is shown that spherical
      aberration of a simple tunable-focus fluidic membrane lens with parabolic
      surfaces can be corrected, which is not possible with a classical spherical lens.
      The presented analysis is explained on examples. Derived formulas make possible
      to calculate parameters of optical systems with fluidic membrane lenses with
      small residual aberrations.

PMID- 23545970
TI  - Heterodyne laser Doppler vibrometers integrated on silicon-on-insulator based on
      serrodyne thermo-optic frequency shifters.
AB  - Miniaturized laser Doppler vibrometers (LDVs) have many advantages over
      conventional bulk LDVs. In this paper, the realization of a miniaturized
      heterodyne LDV integrated on silicon-on-insulator substrate is reported. The
      optical frequency shifters in these on-chip LDVs employ a serrodyne technique,
      and they generate a frequency shift at 2 kHz. Vibrations of a mirror for the
      frequency range between 1.1 and 123 Hz and the velocity range between 0.8 and 400
      MUm/s are measured by both an on-chip LDV and a commercial LDV. The measurement
      results agree well. A compensation method for the influence of on-chip spurious
      reflections is also demonstrated.

PMID- 23545971
TI  - Coded aperture snapshot spectral polarization imaging.
AB  - We describe a single-shot polarization spectral imager that combines two
      birefringent crystals with a binary coded aperture to encode the spatial,
      spectral and polarization data cube for compressive sampling on a two-dimensional
      (2D) detector array. We use a total variation prior to reconstruct the four
      dimensional (4D) data cube from the single 2D measurement. The 4D data cube
      includes 1500*1240 pixels in the spatial domain, 19 wavelength channels between
      400 and 680 nm and two Stokes parameters.

PMID- 23545972
TI  - Light-folded projection three-dimensional display.
AB  - A light-folded projection three-dimensional (3D) display system with a single
      projection lens and a rectangular light tunnel which is composed of four folding
      mirrors on its inside walls is proposed. It is theoretically shown through the
      Wigner distribution function analysis that the proposed system can generate the
      same light field effectively as that of the conventional projection-type
      multiview 3D display system with plural projection lenses. Multiview 3D imaging
      of the proposed system configuration is experimentally demonstrated.

PMID- 23545973
TI  - High-contrast and narrow-linewidth resonant profile for continuous operation
      atomic clock.
AB  - We report a high-contrast and narrow-linewidth resonant line profile by measuring
      the magneto-optical rotation of the transmitted light in a forward-scattering
      arrangement. We also report the splitting of the transmitted line profile at a
      strong microwave excitation. This profile may provide a good competitive scheme
      for the passive Rb frequency standard.

PMID- 23545974
TI  - Feasibility study of integral property retrieval for tropospheric aerosol from
      Raman lidar data using principal component analysis.
AB  - A method is introduced to derive integral properties of the aerosol size
      distribution, e.g., aerosol mass, from tropospheric multiwavelength Raman lidar
      aerosol extinction and backscatter data, using an adapted form of the principal
      component analysis (PCA) technique. Since the refractive index of general
      tropospheric aerosols is variable and aerosol types can vary within one profile,
      an inversion technique applied in the troposphere should account for varying
      aerosol refractive indices. Using PCA, if a sufficiently complete set of
      appropriate refractive index dependent kernels is used, no a priori information
      about the aerosol type is necessary for the inversion of integral properties. In
      principle, the refractive index itself can be retrieved, but this quantity is
      more sensitive to measurement errors than the various integral properties of the
      aerosol size distribution. Here, the PCA technique adapted for use in the
      troposphere is introduced, the refractive index information content of the kernel
      sets is investigated, and error analyses are presented. The technique is then
      applied to actual tropospheric Raman lidar measurements.

PMID- 23545975
TI  - Impact of temporal and spectral aberrations on coherent beam combination of
      nanosecond fiber lasers.
AB  - The effects of aberrations on coherent beam combination (CBC) of nanosecond fiber
      lasers are analyzed in this paper. These effects include imperfect overlap of the
      pulses, spectral phase shift, and nonlinear phase shift, which are induced by
      optical path difference and self-phase modulation. A typical system of CBC of two
      lasers is calculated in detail and design guidelines are given.

PMID- 23545976
TI  - Investigations on the catastrophic damage in multilayer dielectric films.
AB  - HfO2/SiO2 coatings are always fluence-limited by a class of rare catastrophic
      failures induced by a nanosecond laser with a wavelength of 1053 nm. The
      catastrophic damage in HfO2/SiO2 coatings behaves as the damage growth with
      repeated laser irradiation, and thus eventually limits the mirror performance.
      Understanding the damage processes and mechanisms associated with the
      catastrophic damage are important for reducing the occurrence of the catastrophic
      failure and allowing the HfO2/SiO2 coatings to survive at the high fluence
      required by high laser systems. The rough damage behavior of the catastrophic
      failure at the proper critical fluence is present. The pit and delamination in
      the catastrophic failure are investigated to find the possible reasons leading to
      the catastrophic failure. The experimental results indicate that nodular defect
      originated from the substrate easily incurs the catastrophic damage. The electric
      field enhancements of the pit and the substrate impurities may contribute to this
      phenomenon. The delamination is always present on the left of the pit when laser
      irradiates from left to right at oblique incidence, which may be related to the
      plasma plume toward the laser incidence.

PMID- 23545977
TI  - Noise removal in extended depth of field microscope images through nonlinear
      signal processing.
AB  - Extended depth of field (EDF) microscopy, achieved through computational optics,
      allows for real-time 3D imaging of live cell dynamics. EDF is achieved through a
      combination of point spread function engineering and digital image processing. A
      linear Wiener filter has been conventionally used to deconvolve the image, but it
      suffers from high frequency noise amplification and processing artifacts. A
      nonlinear processing scheme is proposed which extends the depth of field while
      minimizing background noise. The nonlinear filter is generated via a training
      algorithm and an iterative optimizer. Biological microscope images processed with
      the nonlinear filter show a significant improvement in image quality and signal
      to-noise ratio over the conventional linear filter.

PMID- 23545978
TI  - Iterative image restoration using nonstationary priors.
AB  - In this paper, we propose an algorithm for image restoration based on fusing
      nonstationary edge-preserving priors. We develop a Bayesian modeling followed by
      an evidence approximation inference approach for deriving the analytic
      foundations of the proposed restoration method. Through a series of
      approximations, the final implementation of the proposed image restoration
      algorithm is iterative and takes advantage of the Fourier domain. Simulation
      results over a variety of blurred and noisy standard test images indicate that
      the presented method comfortably surpasses the current state-of-the-art image
      restoration for compactly supported degradations. We finally present experimental
      results by digitally refocusing images captured with controlled defocus,
      successfully confirming the ability of the proposed restoration algorithm in
      recovering extra features and rich details, while still preserving edges.

PMID- 23545979
TI  - Higher-order computational model for coded aperture spectral imaging.
AB  - Coded aperture snapshot spectral imaging systems (CASSI) sense the three
      dimensional spatio-spectral information of a scene using a single two-dimensional
      focal plane array snapshot. The compressive CASSI measurements are often modeled
      as the summation of coded and shifted versions of the spectral voxels of the
      underlying scene. This coarse approximation of the analog CASSI sensing phenomena
      is then compensated by calibration preprocessing prior to signal reconstruction.
      This paper develops a higher-order precision model for the optical sensing in
      CASSI that includes a more accurate discretization of the underlying signals,
      leading to image reconstructions less dependent on calibration. Further, the
      higher-order model results in improved image quality reconstruction of the
      underlying scene than that achieved by the traditional model. The proposed higher
      precision computational model is also more suitable for reconfigurable multiframe
      CASSI systems where multiple coded apertures are used sequentially to capture the
      hyperspectral scene. Several simulations and experimental measurements
      demonstrate the benefits of the discretization model.

PMID- 23545980
TI  - Image formation analysis and high resolution image reconstruction for plenoptic
      imaging systems.
AB  - Plenoptic imaging systems are often used for applications like refocusing,
      multimodal imaging, and multiview imaging. However, their resolution is limited
      to the number of lenslets. In this paper we investigate paraxial, incoherent,
      plenoptic image formation, and develop a method to recover some of the resolution
      for the case of a two-dimensional (2D) in-focus object. This enables the recovery
      of a conventional-resolution, 2D image from the data captured in a plenoptic
      system. We show simulation results for a plenoptic system with a known response
      and Gaussian sensor noise.

PMID- 23545981
TI  - Fast lapped block reconstructions in compressive spectral imaging.
AB  - The coded aperture snapshot spectral imager (CASSI) senses the spatial and
      spectral information of a scene using a set of K random projections of the scene
      onto focal plane array measurements. The reconstruction of the underlying three
      dimensional (3D) scene is then obtained by l1 norm-based inverse optimization
      algorithms such as the gradient projections for sparse reconstruction (GPSR). The
      computational complexity of the inverse problem in this case grows with order
      O(KN4L) per iteration, where N2 and L are the spatial and spectral dimensions of
      the scene, respectively. In some applications the computational complexity
      becomes overwhelming since reconstructions can take up to several hours in
      desktop architectures. This paper presents a mathematical model for lapped block
      reconstructions in CASSI with O(KB4L) complexity per GPSR iteration where B?N is
      the block size. The approach takes advantage of the structure of the sensing
      matrix thus allowing the independent recovery of smaller overlapping blocks
      spanning the measurement set. The reconstructed 3D lapped parallelepipeds are
      then merged to reduce the block-artifacts in the reconstructed scenes. The full
      data cube is reconstructed with complexity O(K(N4/(N')2)L), per iteration, where
      N'=?N/B?. Simulations show the benefits of the new model as data cube
      reconstruction can be accelerated by an order of magnitude. Furthermore, the
      lapped block reconstructions lead to comparable or higher image reconstruction
      quality.

PMID- 23545982
TI  - Compressive hyperspectral imaging by random separable projections in both the
      spatial and the spectral domains.
AB  - An efficient method and system for compressive sensing of hyperspectral data is
      presented. Compression efficiency is achieved by randomly encoding both the
      spatial and the spectral domains of the hyperspectral datacube. Separable sensing
      architecture is used to reduce the computational complexity associated with the
      compressive sensing of a large volume of data, which is typical of hyperspectral
      imaging. The system enables optimizing the ratio between the spatial and the
      spectral compression sensing ratios. The method is demonstrated by simulations
      performed on real hyperspectral data.

PMID- 23545983
TI  - Bounding pixels in computational imaging.
AB  - We consider computational imaging problems where we have an insufficient number
      of measurements to uniquely reconstruct the object, resulting in an ill-posed
      inverse problem. Rather than deal with this via the usual regularization
      approach, which presumes additional information which may be incorrect, we seek
      bounds on the pixel values of the reconstructed image. Formulating the inverse
      problem as an optimization problem, we find conditions for which a system's
      measurements can produce a bounded result for both the linear case and the non
      negative case (e.g., intensity imaging). We also consider the problem of
      selecting measurements to yield the most bounded results. Finally we simulate
      examples of the application of bounded estimation to different two-dimensional
      multiview systems.

PMID- 23545984
TI  - Adaptive method of dim small object detection with heavy clutter.
AB  - This paper investigates an adaptive method of dim small target detection in
      infrared images with a complex background. We analyze in depth the
      characteristics of the background, the target, and the noise in the gray
      intensity, space and frequency domain of the images. The modified top-hat
      transformation using interrelated structuring elements is adopted to adaptively
      detect the darker and the brighter targets and greatly suppress the cluttered
      background. Lateral pattern inhibition enhances the local contrast ratio and
      simultaneously identifies the targets of interest. The automatic threshold is
      used to enhance real dim targets in the cluttered background. A simulation based
      on the proposed algorithm is carried out and the results prove that the algorithm
      is effective and valid.

PMID- 23545985
TI  - Adaptive centroid-finding algorithm for freeform surface measurements.
AB  - Wavefront sensing systems measure the slope or curvature of a surface by
      calculating the centroid displacement of two focal spot images. Accurately
      finding the centroid of each focal spot determines the measurement results. This
      paper studied several widely used centroid-finding techniques and observed that
      thresholding is the most critical factor affecting the centroid-finding accuracy.
      Since the focal spot image of a freeform surface usually suffers from various
      types of image degradation, it is difficult and sometimes impossible to set a
      best threshold value for the whole image. We propose an adaptive centroid-finding
      algorithm to tackle this problem and have experimentally proven its effectiveness
      in measuring freeform surfaces.

PMID- 23545986
TI  - Multiple-frame photography for extended depth of field.
AB  - For extending the depth of field, we analyze the result of superimposing several
      snapshots, which are taken while changing the amount of focus error, at full
      pupil aperture. We unveil the use of a varifocal lens for controlling the amount
      of focus error, without modifying either the lateral magnification or light
      throughput. After recording a set of snapshots, we use suitable acquisition
      factors for shaping an optical transfer function, which has reduced sensitivity
      to focus errors.

PMID- 23545987
TI  - Phase retrieval using nonlinear diversity.
AB  - We extend the Gerchberg-Saxton algorithm to phase retrieval in a nonlinear
      system. Using a tunable photorefractive crystal, we experimentally demonstrate
      the noninterferometric technique by reconstructing an unknown phase object from
      optical intensity measurements taken at different nonlinear strengths.

PMID- 23545988
TI  - Enhancing layered 3D displays with a lens.
AB  - We augment layered three-dimensional (3D) displays using a lens placed in front
      of or between attenuation layers. The lens, or similar optical element, improves
      the angular resolution of the system and enables translation of the displayed
      scene from a near-field image to a far-field projection. We analyze the relation
      between angular resolution (scene depth) and the number of layers and
      characterize the phase-space trade-offs between spatial and angular frequency
      components. We also introduce an algorithm for determining the layers of the
      display, which significantly reduces the computational requirements. The method
      is demonstrated on a standard 4D light field scene.

PMID- 23545990
TI  - gamma-Catenin is expressed throughout normal human hematopoietic development and
      is required for normal PU.1-dependent monocyte differentiation.

PMID- 23545989
TI  - Interaction of local anesthetics with the K (+) channel pore domain: KcsA as a
      model for drug-dependent tetramer stability.
AB  - Local anesthetics and related drugs block ionic currents of Na (+) , K (+) and Ca
      ( 2+) conducted across the cell membrane by voltage-dependent ion channels. Many
      of these drugs bind in the permeation pathway, occlude the pore and stop ion
      movement. However channel-blocking drugs have also been associated with decreased
      membrane stability of certain tetrameric K (+) channels, similar to the
      destabilization of channel function observed at low extracellular K (+)
      concentration. Such drug-dependent stability may result from electrostatic
      repulsion of K (+) from the selectivity filter by a cationic drug molecule bound
      in the central cavity of the channel. In this study we used the pore domain of
      the KcsA K (+) channel protein to test this hypothesis experimentally with a
      biochemical assay of tetramer stability and theoretically by computational
      simulation of local anesthetic docking to the central cavity. We find that two
      common local anesthetics, lidocaine and tetracaine, promote thermal dissociation
      of the KcsA tetramer in a K (+) -dependent fashion. Docking simulations of these
      drugs with open, open-inactivated and closed crystal structures of KcsA yield
      many energetically favorable drug-channel complexes characterized by nonbonded
      attraction to pore-lining residues and electrostatic repulsion of K (+) . The
      results suggest that binding of cationic drugs to the inner cavity can reduce
      tetramer stability of K (+) channels.

PMID- 23545991
TI  - Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell,
      follicular and transformed lymphoma: a phase II clinical trial.
AB  - Lenalidomide-rituximab therapy is effective in grade 1-2 follicular and mantle
      cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL),
      transformed large cell lymphoma (TL) and grade 3 follicular lymphoma (FLG3) is
      unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL
      (n=32), TL (n=9) or FLG3 (n=4) who had received 1-4 prior lines of treatment were
      given 20 mg oral lenalidomide on days 1-21 of each 28-day cycle, and intravenous
      rituximab (375 mg/m(2)) weekly during cycle 1. Grade 3/4 hematological toxicities
      included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia
      (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7
      52.0 months). Overall response (OR) rate was 33%; median response duration was
      10.2 months. Median progression-free survival (PFS) and overall survival (OS)
      were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three
      partial response (PR), six complete response (CR)) proceeded with stem cell
      transplantation (SCT) and were censored at the time of transplantation. When data
      were analyzed without censoring, median PFS remained 3.7 months and response
      duration increased to 30.9 months. Rituximab plus oral lenalidomide is well
      tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT
      after lenalidomide-rituximab is associated with prolonged response duration. 

PMID- 23545992
TI  - Resistance training controls arterial blood pressure in rats with L-NAME- induced
      hypertension.
AB  - BACKGROUND: Arterial hypertension is a multifactorial chronic condition caused by
      either congenital or acquired factors. OBJECTIVE: To evaluate the effects of
      Resistance Training (RT) on arterial pressure, and on vascular reactivity and
      morphology, of L-NAME-treated hypertensive rats. METHODS: Male Wistar rats (200 -
      250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive
      (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L
      NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was
      evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10
      repetitions, 3 times per week for four weeks. Vascular reactivity was measured in
      rat mesenteric artery rings by concentration-response curves to sodium
      nitroprusside (SNP); phenylephrine (PHE) was also used for histological and
      stereological analysis. RESULTS: Resistance training inhibited the increase in
      mean and diastolic arterial pressures. Significant reduction was observed in Rmax
      (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries
      demonstrated normal intima, media and adventitia layers in all groups.
      Stereological analysis demonstrated no significant difference in luminal, tunica
      media, and total areas of arteries in the SH and TH groups when compared to the
      SN group. Wall-to-lumen ratio of SH arteries was significantly different compared
      to SN arteries (p<0.05) but there was no difference when compared to TH arteries.
      CONCLUSIONS: RT was able to prevent an increase in blood pressure under the
      conditions in this study. This appears to involve a vasoconstrictor regulation
      mechanism and maintenance of luminal diameter in L-NAME induced hypertensive
      rats.

PMID- 23545993
TI  - Peripheral artery disease and kidney function in hypertensive patients.
AB  - BACKGROUND: Patients with peripheral arterial disease (PAD) have a high risk of
      developing cardiovascular events. There is a high prevalence of PAD in
      individuals with kidney disease and both are important risk factors for
      cardiovascular events. OBJECTIVE: The aim of this study was to investigate the
      association between PAD and renal function in hypertensive patients. METHODS: The
      sample consisted of 909 individuals with arterial hypertension. The presence of
      PAD was evaluated using the ankle-brachial index (ABI) method and renal function
      was assessed based on the estimated glomerular filtration rate (eGFR). The
      subjects were divided into groups, according to abnormal (ABI < 0.9) and normal
      ABI (ABI 0.9-1.4). RESULTS: The percentage of subjects with abnormal ABI was 8%.
      In the group of individuals with abnormal ABI, prevalence of CKD was 23.4%,
      compared to a prevalence of 11.2% in patients with normal ABI. Multivariable
      logistic regression analysis, after adjusting the model to the conventional
      cardiovascular risk factors, identified a statistically significant and
      independent effect of eGFR on the likelihood of developing PAD, with an OR of
      0.987 (CI: 0.97-1.00). CONCLUSION: An independent association between PAD and
      chronic kidney disease was observed in the present study. Therefore, the
      combination of an accurate diagnosis of kidney disease and routine ABI evaluation
      could constitute a more efficient means to identify subclinical PAD, allowing
      individuals to benefit from early interventions, aiming at reducing
      cardiovascular risk.

PMID- 23545994
TI  - Effect of mitral valve repair on cardiopulmonary exercise testing variables in
      patients with chronic mitral regurgitation.
AB  - BACKGROUND: Mitral valve repair is the surgical procedure of choice for patients
      with chronic Mitral Regurgitation (MR). The good early and late results allow
      surgical indication before symptom onset. The cardiopulmonary exercise test
      (CPET) can objectively assess functional capacity, but little is known about the
      effect of surgery on their variables. OBJECTIVE: Evaluate the effects of mitral
      repair on CPET variables in patients with chronic MR. METHODS: A total of 47
      patients with severe MR were selected; these patients underwent mitral valve
      repair and were submitted to CPET +/- 30 days before surgery, as well as six to
      12 months after the surgery. RESULTS: There was predominance of functional class
      I or II NYHA in 30 (63.8%) and 34 patients (72.3%), respectively. A significant
      decrease in oxygen consumption (VO2) was observed after surgery, from 1,719 +/-
      571 to 1609 +/- 428 mL min-1, p = 0.036. There was a decrease in Oxygen Uptake
      Efficiency Slope (OUES) from 1,857 +/- 594 to 1763 +/- 514, p = 0.073 and oxygen
      pulse (O2) increased after surgery, from 11.1 +/- 3.2 to 11.9 +/- 3, 2 mL.beat-1
      (p = 0.003). CONCLUSION: The mitral valve repair did not increase peak VO2 and
      OUES despite positive cardiac remodeling observed seven months after surgery.
      However, O2 pulse increased postoperatively, suggesting improved LV systolic
      performance. The CPET is a useful tool to assist in the medical management of
      patients with MR.

PMID- 23545995
TI  - Implementation of the myocardial infarction system of care in city of Belo
      Horizonte, Brazil.
AB  - BACKGROUND: The creation of an acute myocardial infarction (AMI) system of care
      aims to optimize the management of patients from early diagnosis to proper and
      timely treatment. OBJECTIVE: To assess the establishment of an AMI System of Care
      in the city of Belo Horizonte, state of Minas Gerais, and its impact on AMI in
      hospital mortality. METHODS: The AMI system of care was established in the city
      of Belo Horizonte between 2010 and 2011, aiming at increasing the access of
      patients of the public health system to the treatment recommended by the existing
      guidelines. The teams at the emergency care units were trained, and the tele
      electrocardiography system was implanted in those units. The primary outcomes of
      this retrospective observational study were the number of admissions and AMI in
      hospital mortality, from 2009 to 2011. RESULTS: During the study period, 294
      professionals were trained and 563 electrocardiograms (ECGs) transmitted from
      emergency care units to coronary care units. A significant reduction was observed
      in the in-hospital mortality rate (12.3% in 2009 versus 7.1% in 2011, p < 0.001),
      while the number of admissions due to AMI remained stable. The mean cost of
      admission increased (mean R$ 2,480.00 versus R$ 3,501.00; p < 0.001), the
      proportion of admissions including intensive care unit stay increased (32.4% in
      2009 versus 66.1% in 2011; p < 0.001), and the number of patients admitted to
      tertiary hospitals increased (47.0% versus 69.6%; p < 0.001). CONCLUSION: The
      establishment of the AMI system of care improved the access of the population to
      proper treatment, thus reducing AMI in-hospital mortality. [corrected].

PMID- 23545996
TI  - Maximal heart rate: influence of sport practice during childhood and adolescence.
AB  - BACKGROUND: The heart rate (HR) achieved at the end of an exercise test (ET) is
      called maximal HR and is known to have clinical and epidemiological relevance.
      For its correct measurement, it is necessary that the ET be truly maximal.
      OBJECTIVE: To evaluate the influence of a history of intense physical activity
      and/or participation in sports competitions during youth on the maximal HR (% of
      age-predicted HR) on a clinical cardiopulmonary exercise test (CPET). METHODS: A
      total of 600 non-athlete individuals (65.8% males) with a mean age of 46 +/- 13.7
      years, under primary prevention of cardiovascular diseases and who underwent
      maximal CPET, were retrospectively selected. Their physical activity profile
      during childhood/adolescence (PAPCA) was classified in scores growing from 0 to
      4, with value 2 corresponding to their respective age-predicted levels. RESULTS:
      None of the 20 individuals with maximal HR values equal to or greater than 200
      bpm had been inactive or somewhat active during childhood/adolescence. A
      significant association was observed between PAPCA scores and maximal HR (% of
      age-predicted HR) (p = 0.02), with a 7-bpm higher value for PAPCA scores 3-4
      (32.9% of the sample) in comparison to PAPCA 0-2. CONCLUSION: Two hypotheses
      exist to explain these results in individuals who had been more active during
      youth: a) persistence of chronic adaptations to training on the cardiac
      chronotropism, or b) higher ability and/or motivation to achieve a truly maximal
      CPET. Information on the physical activity profile during childhood / adolescence
      may contribute to the interpretation of maximal HR on ET.

PMID- 23545997
TI  - Not just words: caring for the patient by caring about language.

PMID- 23545998
TI  - Systems biology and pediatric research.

PMID- 23545999
TI  - Isolation of five new flavonoids from Melicope triphylla.
AB  - Five new flavonoids, 5,8-dihydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone (1),
      7-hydroxy-3,5-dimethoxy-3',4'-methylenedioxyflavone (2), 7-(2,3-dihydroxy-3
      methylbutoxy)-3,5-dimethoxy-3',4'-methylenedioxyflavone (3), 7-(2,3-dihydroxy-3
      methylbutoxy)-3,3',4',5-tetramethoxyflavone (4), and 7-(2,3-dihydroxy-3
      methylbutoxy)-3,3',4',5,8-pentamethoxyflavone (5), were isolated from the leaves
      of Melicope triphylla. In addition, six known flavonoids were detected: 3,4',5
      trihydroxy-3',7,8-trimethoxyflavone (6), 5,7-dihydroxy-3-methoxy-3',4'
      methylenedioxyflavone (7), 4',5,7-trihydroxy-3,3'-dimethoxyflavone (8), 4',7
      dihydroxy-3,3',5,8-tetramethoxyflavone (9), 4',7-dihydroxy-3,3',5
      trimethoxyflavone (10), and 4',5,7-trihydroxy-3,3',8-trimethoxyflavone (11). The
      new compound structures were determined by spectroscopic methods. Compounds 1-5
      did not exhibit any ichthyotoxic activity against Japanese killifish (medaka in
      Japanese) (Oryzias latipes var.) at 10 ppm.

PMID- 23546001
TI  - In vitro anti-propionibacterium activity by curcumin containing vesicle system.
AB  - Propionibacterium acnes acts a critical role in the development of inflammatory
      acne when it overgrows in pilosebaceous units. The spread of multiple drug
      resistance bacteria indicates a growing need for new antimicrobial agents. The
      objective of this study is to develop lipid vehicles to deliver curcumin and
      inhibit P. acnes in the skin. The inhibitory activities of the curcumin
      containing vehicles against P. acnes were studied by the bioluminescence assay.
      Curcumin accumulation patterns in neonate pig skin were studied using Franz
      diffusion cells and confocal laser scanning microscopy. The physicochemical
      properties of the curcumin containing vehicles including interfacial tension,
      size distribution and viscosity were analyzed. Significant curcumin accumulation
      (362+/-8 ug/g skin) was observed with the lipid vehicles developed herein.
      Curcumin (0.43 ug/mL) in the vehicles significantly inhibited the growth of P.
      acnes. Confocal laser scanning microscopy confirmed the formation of curcumin
      reservoir in the skin by the curcumin-loaded vehicles. Curcumin-loaded vehicles
      could efficiently accumulate in the skin and inhibit P. acnes in vitro. Our
      results highlight the potential of using vehicles containing lauric acid and
      curcumin as an alternative treatment for acne vulgaris.

PMID- 23546000
TI  - Modulating the cyclic guanosine monophosphate substrate selectivity of the
      phosphodiesterase 3 inhibitors by pyridine, pyrido[2,3-d]pyrimidine derivatives
      and their effects upon the growth of HT-29 cancer cell line.
AB  - Analogues with the scaffolds of 3-cyano-4-alkoxyphenyl-6-bromoaryl-2-pyridone and
      2-amino-3-cyano-4-alkoxyphenyl-6-bromoarylpyridine were synthesized. Cyclization
      of the 2-amino derivatives with formic acid and formamide gave the corresponding
      pyrido[2,3-d]pyrimidin-4(3H)-one and the pyrido[2,3-d]-pyrimidin-4-amine
      derivatives, respectively. Active phosphodiesterase 3 (PDE3) inhibitors were
      identified from each of the four aforementioned scaffolds. This is the first
      report that pyrido[2,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4-amine
      derivatives can inhibit PDE3. The analogues with the pyridone and pyrido[2,3
      d]pyrimidin-4(3H)-one scaffolds inhibited both cAMP and cyclic guanosine
      monophosphate (cGMP) hydrolysis by PDE3, while the amine containing scaffolds
      were more selective for cGMP hydrolysis. This observation may set the base for
      substrate-selective pharmacological modulation of this important class of drug
      targets and with less side effects, particularly tachcardia. The dual inhibitors
      of PDE3 were more potent inhibitor towards the growth of HT-29 cancer cell lines.

PMID- 23546002
TI  - Influence of lipid composition on the structural stability of g-protein coupled
      receptor.
AB  - beta2 Adrenergic receptor (beta2AR) is a kind of G-protein coupled receptors
      (GPCRs) which transduce a wide range of extracellular signals into intracellular
      messages responsible for the regulation of diverse cell functions. Because of
      their functional ubiquity, GPCR is one of the most important drug targets in
      pharmaceutical industry. Although recent crystallographic studies provided both
      the active and the inactive states of some families of GPCRs, the influence of
      lipid composition of bilayer membrane on their activation is still poorly
      understood. In this work, we address the influence of lipid composition on the
      structural stability of GPCR, performing molecular dynamics simulations of three
      kinds of states: apo-, and agonist epinephrine-, or antagonist alprenolol-bound
      beta2AR. These three kinds of beta2ARs were embedded in four types of lipid
      membranes: (i) pure palmitoyl-oleoyl-phosphatidyl-choline (POPC), (ii)
      POPC/cholesterol (CHL), (iii) POPC/CHL/GM1 (GM1 ganglioside), (iv) POPC/palmitoyl
      oleoyl-phosphatidyl-ethanolamine (POPE)/CHL/sphingomyeline (SM). The side chains
      of Lys267(6.29) and Asp331(7.58) showed different conformations among the three
      states in all types of lipid membranes. The distances between Lys267(6.29) and
      Asp331(7.58) of apo- and alprenolol-bound beta2ARs are smaller than that of the
      epinephrine-bound beta2AR. In contrast, beta2ARs in POPC/CHL bilayer were
      unstable in which the salt bridge; i.e., ionic lock, was not formed between
      Arg131(3.50) and Glu268(6.30). We have also examined the distribution of lipid
      molecules. A stable hydrophobic interaction between CHL and beta2AR was observed
      at transmembrane helix5 in POPC/CHL/GM1 and POPC/POPE/CHL/SM membranes. These
      results suggest that the lipid composition strongly affects the conformation of
      GPCR and essentially concerns the GPCR activation.

PMID- 23546003
TI  - Synthesis of 2,3-bis(halomethyl)quinoxaline derivatives and evaluation of their
      antibacterial and antifungal activities.
AB  - Quinoxaline derivatives having bis(fluoromethyl), bis(chloromethyl), or
      bis(iodomethyl) groups at the 2- and 3-positions, and various electron
      donating/withdrawing substituents at the 6- and/or 7-positions, were synthesized.
      Their antibacterial and antifungal activities were evaluated by means of minimum
      inhibitory concentration assays. The relationships between the substituents and
      the antimicrobial activities of the quinoxaline derivatives indicate that the
      electrophilicity of the halomethyl units plays an important role in generating
      the antimicrobial activity.

PMID- 23546004
TI  - Medicinal flowers. XXXVIII. structures of acylated sucroses and inhibitory
      effects of constituents on aldose reducatase from the flower buds of Prunus mume.
AB  - The methanolic extract from the flower buds of Prunus mume, cultivated in
      Zhejiang province, China, showed an inhibitory effect on aldose reductase. From
      the methanolic extract, five new acylated sucroses, mumeoses F-J, were isolated
      together with 29 known compounds. The chemical structures of the new compounds
      were elucidated on the basis of chemical and physicochemical evidence. The
      inhibitory effects of the isolated compounds on aldose reductase were also
      investigated. Acylated quinic acid analogs, which are one of the major compounds
      of the flower buds of P. mume, were shown to substantially inhibit aldose
      reductase. In particular, mumeic acid-A was found to exhibit a potent inhibitory
      effect [IC50=0.4 um].

PMID- 23546005
TI  - Concise synthesis of a probe molecule enabling analysis and imaging of vizantin.
AB  - Trehalose 6,6'-dicorynomycolate (TDCM) was first characterized in 1963 as a cell
      surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows
      potent anti-tumor activity due to its immunoadjuvant properties. Furthermore, the
      toxicity of TDCM in mice is much weaker than the related trehalose diester of
      mycolic acid; trehalose 6,6'-dimycolate (TDM, formerly known as cord factor). We
      have investigated the chemical modification of this class of compound to generate
      novel agents that display increased immunoadjuvant activity with minimal
      associated toxicity. During the course of this work we recently developed 6,6'
      bis-O-(3-nonyldodecanoyl)-alpha,alpha'-trehalose (designated as vizantin). Our
      results show that vizantin exhibited a potent prophylactic effect on experimental
      lung metastasis of B16-F0 melanoma cells without a loss of body weight and death
      in mice. Furthermore, vizantin effectively stimulated human macrophages in an in
      vitro model, making it a promising candidate for a safe adjuvant in clinical
      applications. In order to elucidate the pharmacokinetics of vizantin, a probe
      molecule with similar activity was developed on the basis of a structure-activity
      relationship (SAR) study with vizantin. The distribution of the probe molecule
      after intravenous administration into a mouse was assessed by macro confocal
      microscopy, where it was found to accumulate in the lungs and liver.

PMID- 23546006
TI  - Niobium(V) chloride catalyzed oxidation of dithioacetals with 30% hydrogen
      peroxide: a concise preparation of bissulfonylmethylene compounds.
AB  - The oxidation of dithioacetals with 16 eq of 30% hydrogen peroxide in the
      presence of 10 mol% niobium(V) chloride at room temperature provides
      bissulfonylmethylenes in high yields.

PMID- 23546007
TI  - Synthesis of gamma- and delta-lactone natural products by employing a trans-cis
      isomerization/lactonization strategy.
AB  - Alkaline hydrolysis of 4-hydroxy- or/and 5-hydroxy-(2E)-alkenoate followed by
      acid treatment gave the corresponding (2E)-alkenoic acids which were subjected to
      lactone formation reaction without further purification. The crude acids were
      treated with 2,4,6-trichlorobenzoyl chloride in pyridine to afford gamma-lactone
      or delta-lactone, respectively, accompanied by trans-cis isomerization. By this
      procedure, (+/-)-(4,5)-trans-5-benzyloxy-2-hexen-4-olide (90% overall yield), (S)
      5-hydroxy-2-penten-4-olide (86% overall yield), (4S,5R)-5-hydroxy-2-hexen-4-olide
      (86% overall yield), (4R,5S)-5-hydroxy-2-hexen-4-olide (82% overall yield), (S)
      parasorbic acid (58% overall yield) and natural product, (5R,7S)-7-hydroxy-2
      octen-5-olide (euscapholide: 20% overall yield) were synthesized.

PMID- 23546008
TI  - Induced production of methyl bromodihydroxyphenyl acetates by the marine-derived
      fungus Aspergillus sp.
AB  - The addition of metal bromides (NaBr and CaBr2) during fermentation of a marine
      isolate of the fungus Aspergillus sp. induced production of two new brominated
      dihydroxyphenylacetic acid derivatives, methyl 2-(6-bromo-3,4
      dihydroxyphenyl)acetate (1) and methyl 2-(2,5-dibromo-3,4-dihydroxyphenyl)acetate
      (2), and a known compound, 2-(3,4-dihydroxyphenyl)acetic acid (3). The structures
      of the two new compounds (1, 2) were assigned through the combination of
      spectroscopic data analyses and comparison with the spectral data of compound 3.
      Compounds 1-3 exhibited potent radical-scavenging activity against 1,1-diphenyl-2
      picrylhydrazyl (DPPH) with IC50 values (14.2, 12.1, 11.0 um, respectively)
      demonstrating greater activity than the positive control (l-ascorbic acid; IC50,
      20.0 um).

PMID- 23546009
TI  - Design, synthesis and antiviral activity of 2-(3-amino-4
      piperazinylphenyl)chromone derivatives.
AB  - Previously, we have confirmed that the antiviral activities of the chromone
      derivatives were controlled by the type as well as the position of the
      substituents attached to the chromone core structure. In the course of our
      ongoing efforts to optimize the antiviral activity of the chromone derivatives,
      we have been attempting to derivatize the chromone scaffold via introduction of
      various substituents. In this proof-of-concept study, we introduced a 3-amino-4
      piperazinylphenyl functionality to the chromone scaffold and evaluated the
      antiviral activities of the resulting chromone derivatives. The synthesized 2-(3
      amino-4-piperazinylphenyl)-chromones showed severe acute respiratory syndrome
      corona virus (SARS-CoV)-specific antiviral activity. In particular, the 2
      pyridinylpiperazinylphenyl substituents provided the resulting chromone
      derivatives with selective antiviral activity. Taken together, this result
      indicates the possible pharmacophoric role of the 2-pyridinylpiperazine
      functionality attached to the chromone scaffold, which warrants further in-depth
      structure-activity relationship study.

PMID- 23546010
TI  - Six new cyclic peptides from the roots of Gypsophila oldhamiana.
AB  - Six new cyclic peptides, gypsophin A-F (1-6), were isolated from Gypsophila
      oldhamiana. Their structures were elucidated by extensive NMR and chemical
      degradation. Compound 3 exhibited moderate activity of antiplatelet aggregation
      in vitro.

PMID- 23546012
TI  - Electric field-assisted delivery of photofrin to human breast carcinoma cells.
AB  - The influence of electroporation on the Photofrin uptake and distribution was
      evaluated in the breast adenocarcinoma cells (MCF-7) and normal Chinese hamster
      ovary cells (CHO) lacking voltage-dependent channels in vitro. Photofrin was used
      at a concentration of 5 and 25 MUM. The uptake of Photofrin was assessed using
      flow cytometry and fluorescence microscopy methods. Cells viability was evaluated
      with crystal violet assay. Our results indicated that electropermeabilization of
      cells, in the presence of Photofrin, increased the uptake of the photosensitizer.
      Even at the lowest electric field intensity (700 V/cm) Photofrin transport was
      enhanced. Flow cytometry results for MCF-7 cells revealed ~1.7 times stronger
      fluorescence emission intensity for cells exposed to Photofrin and electric field
      of 700 V/cm than cells treated with Photofrin alone. Photofrin was effective only
      when irradiated with blue light. Our studies on combination of photodynamic
      reaction with electroporation suggested improved effectiveness of the treatment
      and showed intracellular distribution of Photofrin. This approach may be
      attractive for cancer treatment as enhanced cellular uptake of Photofrin in MCF-7
      cells can help to reduce effective dose of the photosensitizer and exposure time
      in this type of cancer, diminishing side effects of the therapy. 

PMID- 23546013
TI  - A multilabel model based on Chou's pseudo-amino acid composition for identifying
      membrane proteins with both single and multiple functional types.
AB  - Predicting membrane protein type is a meaningful task because this kind of
      information is very useful to explain the function of membrane proteins. Due to
      the explosion of new protein sequences discovered, it is highly desired to
      develop efficient computation tools for quickly and accurately predicting the
      membrane type for a given protein sequence. Even though several membrane
      predictors have been developed, they can only deal with the membrane proteins
      which belong to the single membrane type. The fact is that there are membrane
      proteins belonging to two or more than two types. To solve this problem, a system
      for predicting membrane protein sequences with single or multiple types is
      proposed. Pseudo-amino acid composition, which has proven to be a very efficient
      tool in representing protein sequences, and a multilabel KNN algorithm are used
      to compose this prediction engine. The results of this initial study are
      encouraging.

PMID- 23546016
TI  - Focus on chemical biology in Asia.

PMID- 23546015
TI  - Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that
      disrupt conserved arginine residues in the voltage sensor.
AB  - KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed
      rectifier K+ current (I Kr) in the heart. KCNH2 mutations cause type 2 long QT
      syndrome (LQT2), which increases the risk for life-threatening ventricular
      arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential
      (AP) by reducing I Kr during repolarization. Kv11.1 contains several conserved
      basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor
      that are important for normal channel trafficking and gating. This study sought
      to determine the mechanism(s) by which LQT2 mutations at conserved arginine
      residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot
      analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested
      that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed
      that R531Q or R531W dramatically altered Kv11.1 current (I Kv11.1) activation,
      inactivation, recovery from inactivation and deactivation. Coexpression of wild
      type (to mimic the patients' genotypes) mostly corrected the changes in I Kv11.1
      activation and inactivation, but deactivation kinetics were still faster.
      Computational simulations using a human ventricular AP model showed that
      accelerating deactivation rates was sufficient to prolong the AP, but these
      effects were minimal compared to simply reducing I Kr. These are the first data
      to demonstrate that coexpressing wild type can correct activation and
      inactivation dysfunction caused by mutations at a critical voltage-sensing
      residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate
      deactivation to cause LQT2 but that the ventricular AP duration is much more
      sensitive to mutations that decrease I Kr. This likely explains why most LQT2
      mutations are nonsense or trafficking-deficient.

PMID- 23546014
TI  - Endothelin-1 stimulates the expression of L-type Ca2+ channels in neonatal rat
      cardiomyocytes via the extracellular signal-regulated kinase 1/2 pathway.
AB  - The cardiac L-type Ca(2+) channel current (I(Ca,L)) plays an important role in
      controlling both cardiac excitability and excitation-contraction coupling and is
      involved in the electrical remodeling during postnatal heart development and
      cardiac hypertrophy. However, the possible role of endothelin-1 (ET-1) in the
      electrical remodeling of postnatal and diseased hearts remains unclear.
      Therefore, the present study was designed to investigate the transcriptional
      regulation of I(Ca,L) mediated by ET-1 in neonatal rat ventricular myocytes using
      the whole-cell patch-clamp technique, quantitative RT-PCR and Western blotting.
      Furthermore, we determined whether the extracellular signal-regulated kinase 1/2
      (ERK1/2) pathway is involved. ET-1 increased I(Ca,L) density without altering its
      voltage dependence of activation and inactivation. In line with the absence of
      functional changes, ET-1 increased L-type Ca(2+) channel pore-forming alpha1C
      subunit mRNA and protein levels without affecting the mRNA expression of
      auxiliary beta- and alpha2/delta-subunits. Furthermore, an actinomycin D chase
      experiment revealed that ET-1 did not alter alpha1C-subunit mRNA stability. These
      effects of ET-1 were inhibited by the ETA receptor antagonist BQ-123 but not the
      ETB receptor antagonist BQ-788. Moreover, the effects of ET-1 on I(Ca,L) and
      alpha1C-subunit expression were abolished by the ERK1/2 inhibitor (PD98059) but
      not by the p38 MAPK inhibitor (SB203580) or the c-Jun N-terminal kinase inhibitor
      (SP600125). These findings indicate that ET-1 increased the transcription of L
      type Ca(2+) channel in cardiomyocytes via activation of ERK1/2 through the ETA
      receptor, which may contribute to the electrical remodeling of heart during
      postnatal development and cardiac hypertrophy.

PMID- 23546017
TI  - Morroniside promotes bone marrow mesenchymal stem cell proliferation in rats.
AB  - The aim of this study was to explore the mechanism underlying the promotive
      effect of morroniside on rat mesenchymal stem cell (RMSC) proliferation and to
      provide an experimental basis for the development of potential new drugs. RMSCs
      were obtained from the bone marrow of Sprague-Dawley rats aged 3-4 months. The
      proliferation of primary and subcultured RMSCs in the high-, medium- and low
      concentration morroniside intervention and blank control groups was observed
      using light microscopy. Cell proliferation and survival conditions were detected
      using methyl thiazolyl tetrazolium (MTT) colorimetric tests. Light microscopy and
      the MTT assay revealed that RMSC adherence time in the morroniside groups was
      shorter compared with that of the control group. Twelve hours after the media of
      primary RMSCs were changed, the number of adherent cells in the morroniside
      groups increased and an elongated cell morphology was observed. The cells at the
      fourth passage in the morroniside groups fused completely 12-16 h after
      inoculation and then rapidly entered into the logarithmic phase. The primary
      RMSCs of the morroniside intervention groups grew into typical bone marrow
      mesenchymal stem cell (BMSC) colonies after 4 days of morroniside treatment and
      their fusion rate had reached 80% after 9-11 days. By contrast, the cell fusion
      rate of the control group only reached 75-80% after 14 days of morroniside
      treatment. Morroniside exhibited a similar promotive effect on proliferation in
      primary and subcultured RMSCs. Morroniside may promote RMSC proliferation through
      secreted factors, cell-to-cell interactions and/or the interactions between
      cellular adhesion molecules and extracellular matrices (ECMs). However, the
      specific mechanism underlying this effect remains to be fully elucidated.

PMID- 23546019
TI  - Acquired irinotecan resistance is accompanied by stable modifications of cell
      cycle dynamics independent of MSI status.
AB  - Irinotecan is a major anticancer agent specifically targeting DNA topoisomerase
      I. Its cytotoxicity is mediated via a two-step process involving accumulation of
      reversible DNA-topoisomerase I complexes associated with transient DNA single
      strand breaks which subsequently are converted into permanent DNA double-strand
      breaks by the replication fork during S phase. Irinotecan may be selectively
      active for treatment of colorectal cancers that show microsatellite instability
      (MSI) due to deficiencies in mismatch repair enzymes, compared to tumors that are
      microsatellite stable but show chromosome instability (CIN). Although the
      clinical activity of irinotecan is principally limited by acquired drug
      resistance, surprisingly little is known about the influence of prolonged
      irinotecan exposure on the cell cycle dynamics. We have developed two colon
      cancer cell lines resistant to SN-38, the active metabolite of irinotecan, one
      derived from HT-29 (CIN), the other from HCT-116 (MSI). We here show that besides
      classical resistance mechanisms, SN-38 resistance is accompanied by an increased
      generation doubling time, a decreased S phase fraction and an increased G2
      fraction in vitro as in tumor xenografts for both CIN and MSI models. As a
      consequence, SN-38-resistant cells and tumors show cross-resistance to the S
      phase selective agent 5-fluorouracil. The resistance is accompanied by increased
      basal levels of gamma-H2AX and phospho-Chk2 without notable changes in the levels
      of phospho-Chk1. Taken together, our results show that prolonged irinotecan
      exposure is accompanied by stable modifications of cell cycle dynamics which
      could have profound impact on tumor sensitivity to a wide range of antitumor
      agents and may influence tumor progression in patients.

PMID- 23546021
TI  - From discrete monomeric complexes to hydrogen-bonded dimeric assemblies based on
      sterically encumbered square planar palladium(II) ONN-pincers.
AB  - The 2-(3-biphenyl-2-ol)-6-iminepyridines, 2-(3-C12H8-2-OH)-6-(CH=NAr)C5H3N (Ar =
      2,6-i-Pr2C6H3 (L1a-H), 2,4,6-Me3C6H2 (L1b-H)), have been prepared in high yield
      via sequential Suzuki coupling, deprotection and condensation reactions from 2
      methoxybiphenyl-3-ylboronic acid and 2-bromo-6-formylpyridine. Treatment of L1-H
      with Pd(OAc)2 or (MeCN)2PdCl2 results in deprotonation of L1-H to afford the
      discrete square planar ONN-chelates, [{2-(3-C12H8-2-O)-6-(CHNAr)C5H3N}Pd(OAc)]
      (Ar = 2,6-i-Pr2C6H3 (1a), 2,4,6-Me3C6H2 (1b)) and [{2-(3-C12H8-2-O)-6
      (CH=NAr)C5H3N}PdCl] (Ar = 2,6-i-Pr2C6H3 (2a), 2,4,6-Me3C6H2 (2b)), in good yield,
      respectively; conversion of 1 to 2 using aqueous sodium chloride has been
      demonstrated. Selective reduction of the imino unit in L1-H with LiAlH4 proceeds
      smoothly to yield the 2-(3-biphenyl-2-ol)-6-(methylamine)pyridines, 2-(3-C12H8-2
      OH)-6-(CH2-NHAr)C5H3N (Ar = 2,6-i-Pr2C6H3 (L2a-H), 2,4,6-Me3C6H2 (L2b-H)), which
      on reaction with Pd(OAc)2 give [{2-(3-C12H8-2-O)-6-(CH2-NHAr)C5H3N}Pd(OAc)] (Ar =
      2,6-i-Pr2C6H3 (3a), 2,4,6-Me3C6H2 (3b)). Depending on the temperature of the
      reaction, the oxidised aldimine products 1a or 1b can also be observed as a
      competitive side-product during the formation of 3a or 3b. Similarly, ketimine
      containing, [{2-(3-C12H8-2-O)-6-(CMe=N(2,6-i-Pr2C6H3))C5H3N}Pd(OAc)] (5), can be
      detected during the preparation of chiral [{2-(3-C12H8-2-O)-6-(CMeH-NH(2,6-i
      Pr2C6H3))C5H3N}Pd(OAc)] (4) from 2-(3-C12H8-2-OH)-6-(CH2-NH(2,6-i-Pr2C6H3))C5H3N
      (L3-H) and Pd(OAc)2. Complexes 3a, 3b and 4 all exist as dimeric species in the
      solid state in which two anti-aligned square planar monomers are held together by
      two intermolecular NH(amine)...O(phenolate) interactions resulting in palladium
      palladium separations of between 3.141-3.284 A. The structurally related chloride
      containing dimeric assemblies, [{2-(3-C12H8-2-O)-6-(CH2-NHAr)C5H3N)}PdCl] (Ar =
      2,6-i-Pr2C6H3 (6a), 2,4,6-Me3C6H2 (6b)), can also be isolated on treatment of 3
      with aqueous sodium chloride or by reaction of L3-H with (MeCN)2PdCl2. Single
      crystal X-ray diffraction studies have been performed on L1a-H, L3-H, 1a, 1b, 2a,
      2b, 3a, 3b, 4, 6a and 6b.

PMID- 23546020
TI  - Expression of receptor tyrosine kinases in esophageal carcinosarcoma.
AB  - Esophageal carcinosarcoma (ECS) is a rare malignant neoplasm associated with a
      poor patient prognosis. It is characterized by the presence of both malignant
      epithelial and mesenchymal components. Molecular-targeted therapy of several
      receptor tyrosine kinases (RTKs) has been reported to be effective in the
      treatment of various malignant tumors, including carcinosarcoma of several
      organs. This study aimed to assess the therapeutic potential of targeting RTKs in
      ECS. Overexpression of RTKs was assessed in 21 ECS cases by immunohistochemistry
      (IHC). Positively stained cases were further examined for RTK gene mutations and
      amplifications by direct sequencing analysis and fluorescence in situ
      hybridization. In epithelial components, KIT, platelet-derived growth factor
      receptor (PDGFR)A, PDGFRB, MET, epidermal growth factor receptor (EGFR) and HER-2
      were overexpressed in 1 (4.8%), 1 (4.8%), 0 (0%), 11 (52.4%), 13 (61.9%) and 2
      (9.5%) cases, respectively. In the mesenchymal components the corresponding
      numbers of cases were 2 (9.5%), 2 (9.5%), 0 (0%), 12 (57.1%), 11 (52.4%) and 0
      (0%). No mutations in the c-kit, PDGFRA and c-met genes were found. Among 19 EGFR
      positive tumors, 2 had EGFR missense mutations (T790A, exon 20) only in the
      mesenchymal component. Gene amplification or high polysomy of c-kit, PDGFRA, c
      met and EGFR was observed in 1 (33.3%), 0 (0%), 3 (18.8%) and 10 (52.6%) cases,
      respectively. In conclusion, various RTKs, particularly MET and EGFR were
      overexpressed in ECSs suggesting that molecular-targeted therapies directed to
      MET, EGFR or other RTKs may be effective in inhibiting the growth or progression
      of the epithelial and/or mesenchymal component of ECS.

PMID- 23546022
TI  - Euthanasia: a matter of life or death?

PMID- 23546018
TI  - Condensin: crafting the chromosome landscape.
AB  - The successful transmission of complete genomes from mother to daughter cells
      during cell divisions requires the structural re-organization of chromosomes into
      individualized and compact structures that can be segregated by mitotic spindle
      microtubules. Multi-subunit protein complexes named condensins play a central
      part in this chromosome condensation process, but the mechanisms behind their
      actions are still poorly understood. An increasing body of evidence suggests
      that, in addition to their role in shaping mitotic chromosomes, condensin
      complexes have also important functions in directing the three-dimensional
      arrangement of chromatin fibers within the interphase nucleus. To fulfill their
      different functions in genome organization, the activity of condensin complexes
      and their localization on chromosomes need to be strictly controlled. In this
      review article, we outline the regulation of condensin function by
      phosphorylation and other posttranslational modifications at different stages of
      the cell cycle. We furthermore discuss how these regulatory mechanisms are used
      to control condensin binding to specific chromosome domains and present a
      comprehensive overview of condensin's interaction partners in these processes.

PMID- 23546023
TI  - Marie Curie (1867-1934): famed female face of science.

PMID- 23546024
TI  - Cytochrome P450 drug interactions with statin therapy.
AB  - Statins are commonly used in the treatment of hyperlipidaemia. Although the
      benefits of statins are well-documented, they have the potential to cause
      myopathy and rhabdomyolysis due to the complex interactions of drugs,
      comorbidities and genetics. The cytochrome P450 family consists of major enzymes
      involved in drug metabolism and bioactivation. This article aims to highlight
      drug interactions involving statins, as well as provide updated recommendations
      and approaches regarding the safe and appropriate use of statins in the primary
      care setting.

PMID- 23546025
TI  - Comparison of risk of malignancy indices in evaluating ovarian masses in a
      Southeast Asian population.
AB  - INTRODUCTION: The risk of malignancy index (RMI) is a scoring system used to
      triage benign from malignant ovarian masses. We compared the specificity and
      sensitivity of the four indices (RMI 1, RMI 2, RMI 3 and RMI 4) to discriminate a
      benign ovarian mass from a malignant one in a Southeast Asian population.
      METHODS: This was a five-year retrospective study of women who were admitted for
      surgery due to ovarian masses. RMI scores were calculated based on standardised
      preoperative cancer antigen (CA)-125 levels, ultrasonography findings, menopausal
      status and tumour size based on ultrasonography. Postoperative histopathologic
      diagnosis was regarded as the definite outcome. Data were analysed using the
      Statistical Package for the Social Sciences, and Mann-Whitney U test was used to
      compare the individual RMI scores between the benign and malignant cases.
      RESULTS: Out of the 480 patients reviewed, 228 women aged 10-65 years were
      included in the study. Of these, 17 (7.5%) had malignant disease and 211 (92.5%)
      had benign pathology. There was no statistical difference in the RMI 1, 2, 3 and
      4 scores between the benign and malignant cases. Individual variables that were
      analysed showed significant differences in median CA-125 level and tumour size (p
      = 0.044 and p < 0.0005, respectively) between the benign and malignant cases.
      CONCLUSION: Our study shows that RMI is not a valuable triage tool for our
      Southeast Asian population. Further prospective validation, with regard to
      standardising results in different patient populations and centres, is required.

PMID- 23546026
TI  - A prospective comparison of chronic primary angle-closure glaucoma versus primary
      open-angle glaucoma in Singapore.
AB  - INTRODUCTION: To describe the optic disc, visual field and ocular characteristics
      of a consecutive cohort of Asian patients with chronic primary angle-closure
      glaucoma (CPACG), and compare them with those having primary open-angle glaucoma
      (POAG). METHODS: In a prospective comparative case series of new patients with
      POAG or CPACG in Singapore, all patients underwent visual acuity assessment, slit
      lamp examination, tonometry, gonioscopy, refraction, Heidelberg Retina Tomograph
      (HRT) and Humphrey visual field (HVF) assessment. RESULTS: 98 patients were
      enrolled (POAG n = 48; CPACG n = 50). CPACG patients were significantly older
      (66.5 +/- 9.2 years vs. 64.1 +/- 13.5 years; p = 0.027) and mostly female (p =
      0.004). CPACG eyes had significantly higher intraocular pressure (26.9 +/- 6.9
      mmHg vs. 24.5 +/- 3.3 mmHg; p = 0.03), shorter axial length (22.89 +/- 0.97 mm
      vs. 24.26 +/- 1.79 mm; p < 0.001) and shallower anterior chamber depth (2.60 +/-
      0.25 mm vs. 3.16 +/- 0.48 mm; p < 0.001). HVF mean deviation or pattern standard
      deviation (PSD) did not differ significantly between POAG and CPACG eyes, but the
      latter had a lower PSD for a given mean deviation. HRT parameters between the two
      groups were not significantly different. CONCLUSION: In this study, CPACG eyes
      had significantly higher presenting intraocular pressure than POAG eyes, but
      there were no significant differences in optic disc topography. A majority of the
      patients in both groups had moderate field defects at the time of presentation,
      followed by severe and then mild defects. The field loss in CPACG eyes was more
      diffuse than that in POAG eyes.

PMID- 23546027
TI  - Sleeping posture and intraocular pressure.
AB  - INTRODUCTION: This prospective observational case series aimed to determine
      whether the lateral decubitus position, which is commonly adopted during sleep,
      has an effect on intraocular pressure (IOP) in normal controls. METHODS: Patients
      without glaucoma were recruited from those visiting outpatient clinics for non
      glaucomatous conditions. The left eye of each patient was included. IOP was first
      measured using Tono-Pen(r) XL applanation tonometer in the supine position,
      following which a second measurement was immediately obtained for the left
      lateral head position. Measurements were obtained with the patient lying on one
      soft and one hard pillow for each position, and patients remained awake during
      these measurements. One tonometry reading was obtained for each position.
      Readings were recorded only when the average of four independent readings
      produced a statistical confidence index of 5%. Results were analysed using the
      paired Student's t-test for comparison of the means. RESULTS: IOP in the left
      lateral decubitus position (17.48 +/- 3.18 mmHg) was significantly higher than in
      the supine position (14.48 +/- 3.09 mmHg) when using soft pillows (p < 0.001).
      When hard pillows were used, IOP in the left lateral decubitus position also
      exceeded that measured in the supine position (16.65 +/- 3.54 mmHg vs. 13.65 +/-
      3.58 mmHg; p < 0.001). There was no statistically significant difference in the
      IOPs measured for the same position when different kinds of pillows were used.
      CONCLUSION: The lateral decubitus position adopted during sleep is associated
      with changes in IOP in healthy volunteers.

PMID- 23546028
TI  - Variations in the posterior division branches of the mandibular nerve in human
      cadavers.
AB  - INTRODUCTION: The lingual, inferior alveolar and auriculotemporal nerves, being
      branches of the posterior division of the mandibular nerve, mainly innervate the
      mandibular teeth and all the major salivary glands. Anomalous communications
      among these branches are widely reported due to their significance to various
      treatment procedures undertaken in the region. This study was performed as
      detailed exploration of the functional perspectives of such communicating
      branches would further enhance the scope of these procedures. METHODS: A total of
      36 specimens were dissected to examine the infratemporal region. The branches
      from the posterior division of the mandibular nerve--namely the lingual, inferior
      alveolar and auriculotemporal nerves--were carefully dissected, and their
      branches were studied and analysed for abnormal course. RESULTS: Communication
      between branches of the posterior division of the mandibular nerve was observed
      in four specimens. In two of the four specimens, communication between the
      mylohyoid and lingual nerves was observed. A rare and seldom reported type of
      communication between the auriculotemporal and inferior alveolar nerves is
      described in this study. This communicating nerve split into two to form a
      buttonhole for the passage of the mylohyoid nerve. CONCLUSION: Such communicating
      branches between nerves found in this study are developmental in origin and
      thought to maintain functional integrity through an alternative route.

PMID- 23546029
TI  - Greater palatine foramen--key to successful hemimaxillary anaesthesia: a
      morphometric study and report of a rare aberration.
AB  - INTRODUCTION: Accurate localisation of the greater palatine foramen (GPF) is
      imperative while negotiating the greater palatine canal for blocking the
      maxillary nerve within the pterygopalatine fossa. The aim of this study was to
      define the position of the foramen relative to readily identifiable intraoral
      reference points in order to help clinicians judge the position of the GPF in a
      consistently reliable manner. METHODS: The GPF was studied in 100 dried, adult,
      unsexed skulls from the state of Maharashtra in western India. Measurements were
      made using a vernier caliper. RESULTS: The mean distances of the GPF from the
      midline maxillary suture, incisive fossa, posterior palatal border and pterygoid
      hamulus were 14.49 mm, 35.50 mm, 3.40 mm and 11.78 mm, respectively. The foramen
      was opposite the third maxillary molar in 73.38% of skulls, and the direction in
      which the foramen opened into the oral cavity was found to be most frequently
      anteromedial (49.49%). In one skull, the greater and lesser palatine foramina
      were bilaterally absent. Except for the invariably present incisive canals, there
      were no accessory palatal foramina, which might have permitted passage of the
      greater palatine neurovascular bundle in lieu of the absent GPF. To the best of
      our knowledge, this is the first study of such a non-syndromic presentation.
      CONCLUSION: The GPF is most frequently palatal to the third maxillary molar. For
      an edentulous patient, the foramen may be located 14-15 mm from the mid-palatal
      raphe or about 12 mm anterior to the palpable pterygoid hamulus.

PMID- 23546030
TI  - Incidence of hydronephrosis in severe uterovaginal or vault prolapse.
AB  - INTRODUCTION: We aimed to evaluate the local incidences of hydronephrosis and
      renal impairment in the presence of severe uterovaginal or vault prolapse, and
      determine whether treatment by surgery or ring pessary resulted in the resolution
      of hydronephrosis in these patients. METHODS: This was a retrospective case study
      of 121 patients who presented with severe uterovaginal or vault prolapse. All
      patients who had fourth degree uterovaginal or vault prolapse, and underwent
      renal ultrasonography and renal function blood tests were included in the study.
      Follow-up imaging for hydronephrosis was performed to determine the outcome after
      patients received treatment. RESULTS: The mean age of the study population was
      66.1 years. The overall incidence of hydronephrosis was 20.6%. The incidence of
      hydronephrosis in patients with severe vault prolapse was 7.1%, while that in
      patients with severe uterovaginal prolapse was 22.4%. Of the 25 patients with
      hydronephrosis, 16 (64.0%) had complete resolution of hydronephrosis after
      treatment, 5 (20.0%) had residual but smaller degrees of hydronephrosis, and 4
      (16.0%) were lost to follow-up. The incidence of renal impairment was 3.3%.
      CONCLUSION: The local incidence of hydronephrosis in patients with severe
      uterovaginal or vault prolapse was 20.6% in our study. We established that 3.3%
      of women with severe uterovaginal or vault prolapse had mild renal impairment.
      Treatment by vaginal surgery for severe uterovaginal or vault prolapse appears to
      result in either complete resolution or improvement of hydronephrosis in the
      majority of patients.

PMID- 23546031
TI  - Cervical screening uptake and its predictors among rural women in Malaysia.
AB  - INTRODUCTION: Cervical cancer is the third most common cancer among Malaysian
      women. However, the uptake of cervical cancer screening--Pap smear--by women in
      Malaysia has been low and remains a challenge. This study was conducted to assess
      the cervical screening practices of rural women in Malaysia and to examine the
      factors associated with such practices. METHODS: A cross-sectional survey was
      conducted in five rural districts in Perak, Malaysia. 1,000 households were
      selected through multistage random sampling. Women aged 20-64 years were
      interviewed by trained enumerators using structured questionnaires. Binomial
      logistic regression was used to identify predictors of cervical screening through
      univariate and multivariate analyses. RESULTS: Among the 959 respondents, only
      48.9% had undergone Pap smear at least once in the past three years. Women in the
      age group 40-49 years (odds ratio 3.027, 95% confidence interval 1.546-5.925; p <
      0.005) were found to be significantly more likely to attend cervical cancer
      screening as compared to those in the age group 20-29 years. Other significant
      predictors were being married with children, having knowledge of cervical cancer
      symptoms, receiving relevant information regarding cervical cancer from health
      personnel or campaigns, being engaged in family planning and receiving
      encouragement from husbands. CONCLUSION: Efforts to boost the uptake of Pap smear
      screening among the rural population should be targeted toward the predictors of
      positive uptake.

PMID- 23546032
TI  - Lifetime cost-effectiveness analysis of ticagrelor in patients with acute
      coronary syndromes based on the PLATO trial: a Singapore healthcare perspective.
AB  - INTRODUCTION: Ticagrelor is a novel antiplatelet drug developed to reduce
      atherothrombosis. The PLATO trial compared ticagrelor and aspirin to clopidogrel
      and aspirin in patients with acute coronary syndromes (ACS). Ticagrelor was found
      to be superior in the primary composite endpoint of cardiovascular death,
      myocardial infarction or stroke, without increasing major bleeding events. The
      current study estimates the lifetime cost-effectiveness of ticagrelor relative to
      generic clopidogrel from a Singapore public healthcare perspective. METHODS: This
      study used a two-part cost-effectiveness model. The first part was a 12-month
      decision tree (using PLATO trial data) to estimate the rates of major
      cardiovascular events, healthcare costs and health-related quality of life. The
      second part was a Markov model estimating lifetime quality-adjusted survival and
      costs conditional on events during the initial 12 months. Daily drug costs
      applied were SGD 1.05 (generic clopidogrel) and SGD 6.00 (ticagrelor). Cost per
      quality-adjusted life years (QALY) was estimated from a Singapore public
      healthcare perspective using life tables and short-term costs from Singapore, and
      long-term costs from South Korea. Deterministic and probabilistic sensitivity
      analyses were performed. RESULTS: Ticagrelor was associated with a lifetime QALY
      gain of 0.13, primarily driven by lower mortality. The resulting incremental cost
      per QALY gained was SGD 10,136.00. Probabilistic sensitivity analysis indicated
      that ticagrelor had a > 99% probability of being cost-effective, given the lower
      recommended WHO willingness-to-pay threshold of one GDP/capita per QALY.
      CONCLUSION: Based on PLATO trial data, one-year treatment with ticagrelor versus
      generic clopidogrel in patients with ACS, relative to WHO reference standards, is
      cost-effective from a Singapore public healthcare perspective.

PMID- 23546033
TI  - Spontaneous cerebrospinal fluid rhinorrhoea: computed tomography and magnetic
      resonance imaging findings.
AB  - Spontaneous cerebrospinal fluid rhinorrhoea is a rare clinical entity. The
      accurate localisation of the leakage site is essential for surgical planning.
      Imaging techniques such as high-resolution computed tomography (CT), CT
      cisternography and magnetic resonance cisternography in variable combinations are
      performed for this purpose. This pictorial essay aims to present the spectrum of
      imaging findings in cases of spontaneous cerebrospinal fluid rhinorrhoea, which
      may be useful for radiologists in the determination of the site of cerebrospinal
      fluid leakage.

PMID- 23546034
TI  - A case of linear morphoea mistaken for reflex sympathetic dystrophy.
AB  - Morphoea, or localised scleroderma, is a disease entity with poorly understood
      pathogenesis. Early diagnosis of the condition is crucial in order to prevent
      permanent morbidity. However, initial presentations of morphoea can be
      nonspecific and easily mistaken for other conditions, resulting in late treatment
      and permanent disability. We report a case of linear morphoea in a 22-year-old
      man who was initially diagnosed with reflex sympathetic dystrophy. By the time
      the diagnosis of morphoea was confirmed, the patient had already developed
      contractures.

PMID- 23546035
TI  - An uncommon case of haemorrhagic enteric fever treated successfully with super
      selective embolisation using polyvinyl alcohol particles and coils.
AB  - Lower gastrointestinal haemorrhage due to enteric fever is uncommon and
      potentially fatal. The majority of patients recover with conservative treatment,
      with surgery reserved for life-threatening bleeding. Given the advances in
      radiologically guided procedures, there have been numerous reports of successful
      embolisation for gastrointestinal haemorrhage, although few of these involved
      enteric fever as the causative agent. We report an uncommon case of haemorrhagic
      enteric fever treated successfully with embolisation using polyvinyl alcohol
      particles and coils.

PMID- 23546036
TI  - A rare case of obstructive azoospermia due to compression of the seminal vesicle
      and ejaculatory duct by a large lower ureteric stone.
AB  - Male infertility due to obstructive azoospermia is a well-known entity. It is
      characterised by obstruction to the outflow of sperms either in the epididymis,
      vas, seminal vesicles or the ejaculatory ducts. We describe a rare case of
      obstructive azoospermia due to compression of the ejaculatory duct and seminal
      vesicle by a large lower ureteric stone in a 30-year-old man who had infertility
      for the past ten years. The patient's azoospermia resolved after removal of the
      stone.

PMID- 23546037
TI  - Tubercular lesion of the foot presenting as epithelioma.
AB  - Tuberculosis continues to be the biggest public health problem worldwide.
      Tuberculosis verrucosa cutis (TVC) is a verrucose form of cutaneous tuberculosis
      that occurs in previously sensitised individuals due to exogenous reinfection
      with Mycobacterium tuberculosis or Mycobacterium bovis, and it reflects good cell
      mediated immunity. An elderly man presented with multiple fungating growths,
      which were painless but associated with mild itching and serous discharge, on the
      right foot for 40 years. The lesions were free from deeper structures and no
      inguinal lymphadenopathy was observed. A provisional diagnosis of epithelioma was
      made based on the features described. However, incisional biopsy indicated that
      the lesions were tuberculous. As part of the anti-tubercular therapy, the lesions
      were excised and the wounds covered with split-thickness skin graft. The
      patient's recovery was uneventful, with no graft loss or infection reported. This
      case illustrates the importance of recognising cutaneous forms of tuberculosis,
      especially TVC, as an important differential diagnosis of epithelioma.

PMID- 23546038
TI  - Difficult intubation in a patient with vallecular cyst.
AB  - Although rare, vallecular cysts can have catastrophic consequences in an
      anaesthetised patient if airway management is inappropriate. We report a case of
      difficult intubation in a 46-year-old man with a vallecular cyst, and detail the
      methods and strategies for successful endotracheal tube insertion. Following a
      review of the current literature, we also discuss airway management options in
      adult patients with vallecular cysts.

PMID- 23546039
TI  - Endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1.
AB  - Endogenous lipoid pneumonia is an uncommon condition. This is a report of a 29
      year-old woman diagnosed with endogenous lipoid pneumonia associated with
      Legionella pneumophila serogroup 1 infection. The patient's endogenous lipoid
      pneumonia resolved completely after treatment for Legionella pneumophila
      infection. This suggests that early diagnosis and aggressive treatment of the
      underlying infection may prevent any long-term sequelae of lipoid pneumonia.

PMID- 23546040
TI  - Rare occurrence of bilateral breast and peritoneal metastases from osteogenic
      sarcoma.
AB  - Breast metastases are uncommon and typically spread from contralateral breast
      carcinomas. Breast metastases that spread from extramammary malignancies are even
      less common, and account for 0.5%-6.6% of all malignant breast disease. As
      extrapulmonary metastases from osteosarcoma are uncommon, breast metastasis from
      osteosarcoma is extremely rare. We report a case of breast and peritoneal
      metastases from a tibial osteosarcoma 18 months after diagnosis, and 9 months
      after surgery and adjuvant chemotherapy. Computed tomography findings of multiple
      calcified and noncalcified tumour deposits in the lungs, pleura, peritoneum,
      chest wall and both breasts are described.

PMID- 23546041
TI  - p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the
      first clinical and molecular report of Indonesian patients.
AB  - Apert syndrome (AS) is a rare autosomal dominant disorder characterised by
      craniosynostosis and limb malformations, and is associated with congenital heart
      disease and other systemic malformations, including intellectual disability. We
      report two Indonesian patients with AS, in whom molecular analysis detected
      p.Ser252Trp (c.755C>G) and p.Pro253Arg (c.758C>G) mutations in the fibroblast
      growth factor receptor 2 (FGFR2) gene, respectively. Although the syndrome has
      been frequently described, this is the first clinical report of AS confirmed by
      molecular analysis in Indonesia. The difference in severity of clinical features
      in the two patients may be consistent with a genotype-phenotype correlation of
      the FGFR2mutation. The management of individuals with AS is best achieved within
      a multidisciplinary setting. However, in most developing countries, early
      intervention may be delayed due to late diagnosis, a lack of facilities and
      financial constraints. This report underpins the benefits of early diagnosis for
      AS management.

PMID- 23546042
TI  - Enhanced power conversion efficiencies in bulk heterojunction solar cells based
      on conjugated polymer with isoindigo side chain.
AB  - A novel conjugated side-chain polymer (PBDT-TID), based on benzo[1,2-b:4,5
      b']dithiophene (BDT) and isoindigo (ID) moieties, was designed and synthesized.
      The new polymer exhibited excellent microphase separation in active layers. Bulk
      heterojunction polymer solar cells fabricated from PBDT-TID and PC61BM showed
      promising power conversion efficiencies of 5.25% and 6.51% using conventional and
      inverted device structures, respectively.

PMID- 23546044
TI  - Rationale for chemotherapy, immunotherapy, and checkpoint blockade in SCLC:
      beyond traditional treatment approaches.
AB  - INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy that
      although initially sensitive to chemo- and radiation therapy, inevitably relapses
      resulting in poor survival. Increasing evidence suggests that immune responses
      against SCLC cells make immunotherapy a viable therapeutic approach. Furthermore,
      preclinical data have shown that certain chemotherapeutic regimens may augment
      the immunotherapeutic response in SCLC. This review discusses current evidence
      supporting immunotherapy for SCLC, progress made, and ongoing clinical trials.
      METHODS: We searched PubMed and abstracts presented at recent oncology congresses
      for publications on the clinical benefit of immunotherapy/checkpoint blockade for
      treatment of SCLC. RESULTS: Preliminary data from ongoing clinical trials in SCLC
      have shown that some antiangiogenic agents, vaccines, and immunomodulators,
      including interferon-alpha and immune checkpoint blockers (i.e., anticytotoxic T
      lymphocyte-associated antigen-4 [CTLA-4] antibodies) may be efficacious as single
      agents and in combination with standard-of-care regimens. Notably, in a phase II
      trial, ipilimumab--a fully human anti-CTLA-4 monoclonal antibody recently
      approved for treatment of unresectable or metastatic melanoma-demonstrated
      encouraging results when used as part of a chemoimmunotherapeutic regimen in
      patients with SCLC. Ipilimumab is undergoing further investigation in this
      population. CONCLUSIONS: Treatment options for SCLC are limited and prognosis
      poor, emphasizing the need for novel treatments. Although current strategies
      successfully induce a response, the response is not durable. Evidence of an
      immune response in SCLC and a better understanding of the immunosuppressive tumor
      environment support the combinatorial use of immunomodulators, such as
      ipilimumab, with traditional chemotherapy regimens to improve patient outcomes
      and potentially sustain the effect from chemotherapeutic induction.

PMID- 23546046
TI  - Phase-preserved optical elevator.
AB  - The unique superiority of transformation optics devices designed from coordinate
      transformation is their capability of recovering both ray trajectory and optical
      path length in light manipulation. However, very few experiments have been done
      so far to verify this dual-recovery property from viewpoints of both ray
      trajectory and optical path length simultaneously. The experimental difficulties
      arise from the fact that most previous optical transformation optics devices only
      work at the nano-scale; the lack of intercomparison between data from both
      optical path length and ray trajectory measurement in these experiments obscured
      the fact that the ray path was subject to a subwavelength lateral shift that was
      otherwise not easily perceivable and, instead, was pointed out theoretically [B.
      Zhang et al. Phys. Rev. Lett. 104, 233903, 2010]. Here, we use a simple
      macroscopic transformation optics device of phase-preserved optical elevator,
      which is a typical birefringent optical phenomenon that can virtually lift an
      optical image by a macroscopic distance, to demonstrate decisively the unique
      optical path length preservation property of transformation optics. The recovery
      of ray trajectory is first determined with no lateral shift in the reflected ray.
      The phase preservation is then verified with incoherent white-light
      interferometry without ambiguity and phase unwrapping.

PMID- 23546045
TI  - Phase 2 study of pemetrexed and itraconazole as second-line therapy for
      metastatic nonsquamous non-small-cell lung cancer.
AB  - INTRODUCTION: Preclinical studies have suggested that the oral antifungal agent
      itraconazole specifically inhibits proliferation, migration, and tube formation
      of endothelial cells. Itraconazole has potent antiangiogenic activity and
      enhances the efficacy of cytotoxic chemotherapy in multiple primary xenograft
      lung cancer models. On the basis of these data, we performed an exploratory
      clinical study, assessing the efficacy of itraconazole with cytotoxic
      chemotherapy in the treatment of patients with advanced lung cancer. METHODS: The
      study enrolled patients with progressive nonsquamous non-small-cell lung cancer
      after one prior cytotoxic therapy for metastatic disease, randomized 2:1 to
      intravenous administration of pemetrexed 500 mg/m2 on day 1, with or without
      itraconazole 200 mg orally daily, on a 21-day cycle. Outcome measures included
      percent progression-free at 3 months, progression-free survival, overall
      survival, and observed toxicity. RESULTS: A total of 23 patients were enrolled;
      the study was stopped early because of increasing use of pemetrexed in the first
      line setting. At 3 months, 67% of the patients on itraconazole plus pemetrexed
      were progression-free versus 29% on the control arm of pemetrexed alone (p =
      0.11). Median progression-free survivals were 5.5 months (itraconazole) versus
      2.8 months (control) (hazard ratio = 0.399, p = 0.089). Overall survival was
      longer in patients receiving itraconazole (median 32 months) versus control (8
      months) (hazard ratio = 0.194, p = 0.012). There were no evident differences in
      toxicity between the study arms. CONCLUSION: Itraconazole is well tolerated in
      combination with pemetrexed. Consistent with our preclinical data, daily
      itraconazole administration is associated with trends suggestive of improved
      disease control in patients receiving chemotherapy for advanced lung cancer.

PMID- 23546047
TI  - Measurements of the group delay and the group delay dispersion with resonance
      scanning interferometer.
AB  - We developed a method for group delay and group delay dispersion measurements,
      based on location of interference resonance peaks. Such resonance peaks can be
      observed in transmittance or in reflectance when two mirrors are placed parallel
      to each other and separated by a thin air spacer. By using a novel approach,
      based on simultaneous processing of the data acquired for different spacer
      distances we obtained reliable results with high resolution. Measurements were
      performed both in transmittance and reflectance layouts depending on the
      reflectivity of the mirror to be measured. The developed method allows dispersion
      measurements of ultraviolet mirrors and ultra-broadband mirrors spanning more
      than one optical octave to be performed.

PMID- 23546048
TI  - Displacement-enhanced entanglement distillation of single-mode-squeezed entangled
      states.
AB  - It has been shown that entanglement distillation of Gaussian entangled states by
      means of local photon subtraction can be improved by local Gaussian
      transformations. Here we show that a similar effect can be expected for the
      distillation of an asymmetric Gaussian entangled state that is produced by a
      single squeezed beam. We show that for low initial entanglement, our largely
      simplified protocol generates more entanglement than previous proposed protocols.
      Furthermore, we show that the distillation scheme also works efficiently on
      decohered entangled states as well as with a practical photon subtraction setup.

PMID- 23546050
TI  - Compact 2D nonlinear photonic crystal source of beamlike path entangled photons.
AB  - We demonstrate a method to generate entangled photons with controlled spatial
      shape by parametric down conversion (PDC) in a 2D nonlinear crystal. A compact
      and novel crystal source was designed and fabricated, generating directly path
      entangled photons without the use of additional beam-splitters. This crystal
      supports two PDC processes, emitting biphotons into two beamlike modes
      simultaneously. Two coherent path entangled amplitudes of biphotons were created
      and their interference observed. Our method enables the generation of entangled
      photons with controlled spatial, spectral and polarization properties.

PMID- 23546049
TI  - Experimental evidence for the formation of divalent ytterbium in the
      photodarkening process of Yb-doped fiber lasers.
AB  - In this work we present experimental evidence that the valence instability of the
      ytterbium ion play a key role for the observed photodarkening mechanism in Yb
      doped fiber lasers. Luminescence and excitation spectroscopy performed on UV
      irradiated Yb/Al doped silica glass preforms and near-infrared diode pumped
      photodarkened fibers show a concentration increase of Yb(2+) ions. A
      concentration decrease in Yb(3+) could also be observed for the UV irradiated
      preform. The findings contribute to an increased understanding of the kinetic
      processes related to photodarkening in Yb-doped high power fiber lasers.

PMID- 23546051
TI  - Light absorber based on nano-spheres on a substrate reflector.
AB  - We systematically study a type of plasmonic light absorber based on a monolayer
      of gold nano-spheres with less than 30 nm in diameters deposited on top of a
      continuous gold substrate. The influences of particle size, inter-particle
      distance, particle-substrate spacer size etc on the resonance are studied
      thoroughly with a 3D finite-element method. We identified that the high
      absorption resonance is mainly due to gap plasmon (coupled through particle
      bodies) when the separation between neighboring nano-spheres is small enough,
      such as close to 1 nm; at larger particle separations, the resonance is dominated
      by particle dipoles (coupled through the host dielectric). Experimentally, an
      absorber was fabricated based on chemically-synthesized gold nanoparticles coated
      with silica shell. The absorber shows a characteristic absorption band around 810
      nm with a maximum absorbance of approximately 90%, which agrees reasonably well
      with our numerical calculation. The fabrication technique can be easily adapted
      for devising efficient light absorbers of large areas.

PMID- 23546052
TI  - Highly efficient heralding of entangled single photons.
AB  - Single photons are an important prerequisite for a broad spectrum of quantum
      optical applications. We experimentally demonstrate a heralded single-photon
      source based on spontaneous parametric down-conversion in collinear bulk optics,
      and fiber-coupled bolometric transition-edge sensors. Without correcting for
      background, losses, or detection inefficiencies, we measure an overall heralding
      efficiency of 83%. By violating a Bell inequality, we confirm the single-photon
      character and high-quality entanglement of our heralded single photons which, in
      combination with the high heralding efficiency, are a necessary ingredient for
      advanced quantum communication protocols such as one-sided device-independent
      quantum key distribution.

PMID- 23546053
TI  - Single SOA based simultaneous amplitude regeneration for WDM-PDM RZ-PSK signals.
AB  - We propose and demonstrate all-optical amplitude regeneration for the wavelength
      division multiplexing and polarization division multiplexing (WDM-PDM) return-to
      zero phase shift keying (RZ-PSK) signals using a single semiconductor optical
      amplifier (SOA) and subsequent filtering. The regeneration is based on the cross
      phase modulation (XPM) effect in the saturated SOA and the subsequent narrow
      filtering. The spectrum of the distorted signal can be broadened due to the phase
      modulation induced by the synchronous optical clock signal. A narrow band pass
      filter is utilized to extract part of the broadened spectrum and remove the
      amplitude noise, while preserving the phase information. The working principle
      for multi-channel and polarization orthogonality preserving is analyzed. 4
      channel dual polarization signals can be simultaneously amplitude regenerated
      without introducing wavelength and polarization demultiplexing. An average power
      penalty improvement of 1.75dB can be achieved for the WDM-PDM signals.

PMID- 23546054
TI  - Dual-rail nanobeam microfiber-coupled resonator.
AB  - A microfiber-coupled dual-rail nanobeam resonator is proposed and demonstrated.
      The dual-rail scheme is employed to encourage the overlap between the light
      emitter and the air mode. The one-dimensional resonant cavity is formed by
      contacting a curved microfiber with the dual-rail nanobeam. The finite width of
      the dual-rail nanobeam turns out to be advantageous for both out-coupling with
      the microfiber and broader tuning of resonant wavelength. By employing InGaAsP
      quantum well gain medium, a simple and robust reconfigurable laser is created.
      Experimentally we measure a quality factor of 11,000 and out-coupling efficiency
      of 30%. The spontaneous emission factor (beta) of the nanobeam laser is measured
      to be 0.16. Computationally we identified a resonant cavity with a quality factor
      over 6 * 10(5) and out-coupling efficiency over 90%.

PMID- 23546055
TI  - Ultra-compact, flat-top demultiplexer using anti-reflection contra-directional
      couplers for CWDM networks on silicon.
AB  - Wavelength-division-multiplexing (WDM) networks with wide channel grids and
      bandwidths are promising for low-cost, low-power optical interconnects. Wide
      bandwidth, single-band (i.e., no free-spectral range) add-drop filters have been
      developed on silicon using anti-reflection contra-directional couplers with out
      of-phase Bragg gratings. Using such filter components, we demonstrate a 4
      channel, coarse-WDM demultiplexer with flat passbands of up to 13 nm and an ultra
      compact size of 1.2 * 10(-3) mm(2).

PMID- 23546056
TI  - Individual loss distribution measurement in 32-branched PON using pulsed pump
      probe Brillouin analysis.
AB  - We describe loss distribution measurement in a passive optical network (PON)
      using pulsed pump-probe Brillouin analysis. A preliminary experiment is
      demonstrated using a 32-branched PON constructed in the laboratory. We analyze
      the signal to noise ratio of this measurement and show that the method can
      realize a 25 dB dynamic range in 90 seconds (10000 times averaging), with an
      event location resolution of 10 m, and a fiber length identification resolution
      of 2 m.

PMID- 23546057
TI  - Silicon-on-insulator narrow-passband filter based on cascaded MZIs incorporating
      enhanced FSR for downconverting analog photonic links.
AB  - A silicon-on-insulator (SOI) narrow-passband filter based on cascaded Mach
      Zehnder interferometers (MZIs) is theoretically simulated and experimentally
      demonstrated, indicating that the free spectral range (FSR) of the proposed
      filter can be significantly enlarged by increasing the number of the MZI stages.
      A filter using three-stage cascaded MZIs structure is successfully realized in
      the experiment and a 3-dB bandwidth of about 1.536 GHz and FSR about 13.5 GHz
      have been achieved. The performance of a downconverting analog photonic link
      (APL) employing the designed filter for microwave signal processing is also
      measured and a spurious free dynamic range (SFDR) as high as 104.1dB-Hz(2/3) is
      observed.

PMID- 23546058
TI  - Interband scattering in a slow light photonic crystal waveguide under electro
      optic tuning.
AB  - The evolution of the transmission spectrum of a photonic crystal waveguide under
      electro-optic tuning was studied in the band of an odd TE-like mode. The spectral
      signature of the interband scattering from the TM-like mode to the odd TE-like
      mode was characterized at various bias levels. The shift of the odd-mode band was
      determined based on a statistical approach to overcome the spectral noise.
      Simulations were performed to explain the spectral shift based on electro-optic
      and thermo-optic effects in the active photonic crystal structures. Potential
      impact of interband scattering on indirect interband-transition-based optical
      isolators is discussed and potential remedies are offered.

PMID- 23546059
TI  - Consistent characterization of semiconductor saturable absorber mirrors with
      single-pulse and pump-probe spectroscopy.
AB  - We study the comparability of the two most important measurement methods used for
      the characterization of semiconductor saturable absorber mirrors (SESAMs). For
      both methods, single-pulse spectroscopy (SPS) and pump-probe spectroscopy (PPS),
      we analyze in detail the time-dependent saturation dynamics inside a SESAM. Based
      on this analysis, we find that fluence-dependent PPS at complete spatial overlap
      and zero time delay is equivalent to SPS. We confirm our findings experimentally
      by comparing data from SPS and PPS of two samples. We show how to interpret this
      data consistently and we give explanations for possible deviations.

PMID- 23546060
TI  - Tunable CW all-fiber optical parametric oscillator operating below 1 MUm.
AB  - CW all-fiber optical parametric oscillator (FOPO) with tuning range from 950 to
      1010 nm is demonstrated using birefringent photonic crystal fiber pumped by an
      Ytterbium-doped fiber laser (YDFL) near 1 MUm. CW parametric generation with
      spectral linewidth of 3.7 nm at 972 nm has been obtained with slope efficiency as
      high as 9.4% and output power of up to 460 mW. It is also shown that the FOPO
      slope efficiency reaches 25% after narrowing of the pump spectrum down to 40 pm.
      At that the generated power exceeds 1 W, but in this case the generated radiation
      is modulated with 48 ns period and 50% duty factor due to pump laser power
      modulation which is probably caused by stimulated Brillouin back scattering.

PMID- 23546061
TI  - Imaging by integrating stitched spectrograms.
AB  - A new diffractive imaging technique called Imaging By Integrating Stitched
      Spectrograms (IBISS) is presented. Both the data collection and phase retrieval
      algorithm used in IBISS are direct extensions of frequency resolved optical
      gating to higher dimensions. Data collection involves capturing an array of
      diffraction patterns generated by scanning a sample across a coherent beam of
      light. Phase retrieval is performed using the Principal Components Generalized
      Projections Algorithm (PCGPA) by reducing the four dimensional data set of images
      to two remapped two-dimensional sets. The technique is successfully demonstrated
      using a Helium Neon laser to image a 350MUm wide sample with 12MUm resolution.

PMID- 23546062
TI  - Simulations of high-Q optical nanocavities with a gradual 1D bandgap.
AB  - High-quality cavities in hybrid material systems have various interesting
      applications. We perform a comprehensive modeling comparison on such a design,
      where confinement in the III-V material is provided by gradual photonic crystal
      tuning, a recently proposed method offering strong resonances. The III-V cavity
      couples to an underlying silicon waveguide. We report on the device properties
      using four simulation methods: finite-difference time-domain (FDTD), finite
      element method (FEM), bidirectional eigenmode propagation (BEP) and aperiodic
      rigorous coupled wave analysis (aRCWA). We explain the major confinement and
      coupling effects, consistent with the simulation results. E.g. for strong
      waveguide coupling, we find quantitative discrepancies between the methods, which
      establishes the proposed high-index-contrast, lossy, 3D structure as a
      challenging modeling benchmark.

PMID- 23546063
TI  - Physical optics solution for the scattering of a partially-coherent wave from a
      statistically rough material surface.
AB  - The scattering of a partially-coherent wave from a statistically rough material
      surface is investigated via derivation of the scattered field cross-spectral
      density function. Two forms of the cross-spectral density are derived using the
      physical optics approximation. The first is applicable to smooth-to-moderately
      rough surfaces and is a complicated expression of source and surface parameters.
      Physical insight is gleaned from its analytical form and presented in this work.
      The second form of the cross-spectral density function is applicable to very
      rough surfaces and is remarkably physical. Its form is discussed at length and
      closed-form expressions are derived for the angular spectral degree of coherence
      and spectral density radii. Furthermore, it is found that, under certain
      circumstances, the cross-spectral density function maintains a Gaussian Schell
      model form. This is consistent with published results applicable only in the
      paraxial regime. Lastly, the closed-form cross-spectral density functions derived
      here are rigorously validated with scatterometer measurements and full-wave
      electromagnetic and physical optics simulations. Good agreement is noted between
      the analytical predictions and the measured and simulated results.

PMID- 23546064
TI  - Optimization of single-cycle terahertz generation in LiNbO3 for sub-50
      femtosecond pump pulses.
AB  - We compare different tilted-pulse-front pumping schemes for single-cycle THz
      generation in LiNbO(3) crystals both theoretically and experimentally in terms of
      conversion efficiency. The conventional setup with a single lens as an imaging
      element has been found to be highly inefficient in the case of sub-50 fs pump
      pulses, mainly due to the resulting chromatic aberrations. These aberrations are
      avoided in the proposed new setup, which employs two concave mirrors in a
      Keplerian telescope arrangement as the imaging sequence. This partially
      compensates spherical aberrations and results in a ca. six times higher
      conversion efficiency in the case of 35-fs optical pump pulse duration compared
      to the single-lens setup. A THz field strength of 60 kV/cm was obtained using 0.5
      mJ pump pulses. The divergence of the THz beam has been found experimentally to
      depend on the pump imaging scheme employed.

PMID- 23546065
TI  - Highly directional thermal emission from two-dimensional silicon structures.
AB  - We simulate, fabricate, and characterize near perfectly absorbing two-dimensional
      grating structures in the thermal infrared using heavily doped silicon (HdSi)
      that supports long wave infrared surface plasmon polaritons (LWIR SPP's). The
      devices were designed and optimized using both finite difference time domain
      (FDTD) and rigorous coupled wave analysis (RCWA) simulation techniques to satisfy
      stringent requirements for thermal management applications requiring high thermal
      radiation absorption over a narrow angular range and low visible radiation
      absorption over a broad angular range. After optimization and fabrication,
      characterization was performed using reflection spectroscopy and normal incidence
      emissivity measurements. Excellent agreement between simulation and experiment
      was obtained.

PMID- 23546066
TI  - Split ring aperture for optical magnetic field enhancement by radially polarized
      beam.
AB  - Inspired by Babinet's principle, we proposed a new plasmonic structure for
      enhancing the optical magnetic field, i.e. split ring aperture, whose complement
      is the well-known split ring. The split ring aperture exhibits a much better
      performance under radially polarized excitation than linearly polarized
      excitation. We attribute the ultra-high intensity enhancement in magnetic field
      to the symmetric matching between the aperture geometry and the direction of the
      electric field vector in each direction of radially excitation. The impact of the
      design parameters on the intensity enhancement and resonant wavelength is also
      investigated in details.

PMID- 23546067
TI  - Two-mirror telescope design with third-order coma insensitive to decenter
      misalignment.
AB  - Misalignments always occur in real optical systems. These misalignments do not
      generate new aberration forms, but they change the aberration field dependence.
      Two-mirror telescopes have been used in several applications. We analyze a two
      mirror telescope configuration that has negligible sensitivity to decenter
      misalignments. By applying the wave aberration theory for plane-symmetric optical
      systems it is shown that the asphericity in the secondary mirror, if properly
      chosen, can compensate for any decenter perturbation allowing third-order coma
      unchanged across the field of view. For any two-mirror system it is possible to
      find a configuration in which decenter misalignments do not generate field
      uniform coma.

PMID- 23546068
TI  - Spectrally tailored narrowband pulses for femtosecond stimulated Raman
      spectroscopy in the range 330-750 nm.
AB  - Spectral compression of femtosecond pulses by second harmonic generation in the
      presence of substantial group velocity dispersion provides a convenient source of
      narrowband Raman pump pulses for femtosecond stimulated Raman spectroscopy
      (FSRS). We discuss here a simple and efficient modification that dramatically
      increases the versatility of the second harmonic spectral compression technique.
      Adding a spectral filter following second harmonic generation produces narrowband
      pulses with a superior temporal profile. This simple modification i) increases
      the Raman gain for a given pulse energy, ii) improves the spectral resolution,
      iii) suppresses coherent oscillations associated with slowly dephasing
      vibrations, and iv) extends the useful tunable range to at least 330-750 nm.

PMID- 23546069
TI  - Capturing reflected cladding modes from a fiber Bragg grating with a double-clad
      fiber coupler.
AB  - We present a novel measurement scheme using a double-clad fiber coupler (DCFC)
      and a fiber Bragg grating (FBG) to resolve cladding modes. Direct measurement of
      the optical spectra and power in the cladding modes is obtained through the use
      of a specially designed DCFC spliced to a highly reflective FBG written into
      slightly etched standard photosensitive single mode fiber to match the inner
      cladding diameter of the DCFC. The DCFC is made by tapering and fusing two double
      clad fibers (DCF) together. The device is capable of capturing backward
      propagating low and high order cladding modes simply and efficiently. Also, we
      demonstrate the capability of such a device to measure the surrounding refractive
      index (SRI) with an extremely high sensitivity of 69.769 +/- 0.035 MUW/RIU and a
      resolution of 1.433 * 10(-5) +/- 8 * 10(-9) RIU between 1.37 and 1.45 RIU. The
      device provides a large SRI operating range from 1.30 to 1.45 RIU with sufficient
      discrimination for all individual captured cladding modes. The proposed scheme
      can be adapted to many different types of bend, temperature, refractive index and
      other evanescent wave based sensors.

PMID- 23546070
TI  - Observation of electromagnetically induced transparency in evanescent fields.
AB  - We observe and investigate, both experimentally and theoretically,
      electromagnetically-induced transparency experienced by evanescent fields arising
      due to total internal reflection from an interface of glass and hot rubidium
      vapor. This phenomenon manifests itself as a non-Lorentzian peak in the
      reflectivity spectrum, which features a sharp cusp with a sub-natural width of
      about 1 MHz. The width of the peak is independent of the thickness of the
      interaction region, which indicates that the main source of decoherence is likely
      due to collisions with the cell walls rather than diffusion of atoms. With the
      inclusion of a coherence-preserving wall coating, this system could be used as an
      ultra-compact frequency reference.

PMID- 23546071
TI  - Large current MOSFET on photonic silicon-on-insulator wafers and its monolithic
      integration with a thermo-optic 2 * 2 Mach-Zehnder switch.
AB  - n-channel body-tied partially depleted metal-oxide-semiconductor field-effect
      transistors (MOSFETs) were fabricated for large current applications on a silicon
      on-insulator wafer with photonics-oriented specifications. The MOSFET can drive
      an electrical current as large as 20 mA. We monolithically integrated this MOSFET
      with a 2 * 2 Mach-Zehnder interferometer optical switch having thermo-optic phase
      shifters. The static and dynamic performances of the integrated device are
      experimentally evaluated.

PMID- 23546072
TI  - Generalized Jones matrices for anisotropic media.
AB  - The interaction of arbitrary three-dimensional light beams with optical elements
      is described by the generalized Jones calculus, which has been formally proposed
      recently [Azzam, J. Opt. Soc. Am. A 28, 2279 (2011)]. In this work we obtain the
      parametric expression of the 3*3 differential generalized Jones matrix (dGJM) for
      arbitrary optical media assuming transverse light waves. The dGJM is intimately
      connected to the Gell-Mann matrices, and we show that it provides a versatile
      method for obtaining the macroscopic GJM of media with either sequential or
      simultaneous anisotropic effects. Explicit parametric expressions of the GJM for
      some relevant optical elements are provided.

PMID- 23546073
TI  - Black silicon: substrate for laser 3D micro/nano-polymerization.
AB  - We demonstrate that black silicon (b-Si) made by dry plasma etching is a
      promising substrate for laser three-dimensional (3D) micro/nano-polymerization.
      High aspect ratio Si-needles, working as sacrificial support structures, have
      flexibility required to relax interface stresses between substrate and the
      polymerized micro-/nano- objects. Surface of b-Si can be made electrically
      conductive by metal deposition and, at the same time, can preserve low optical
      reflectivity beneficial for polymerization by direct laser writing. 3D laser
      polymerization usually performed at the irradiation conditions close to the
      dielectric breakdown is possible on non-reflective and not metallic surfaces.
      Here we show that low reflectivity and high metallic conductivity are not counter
      exclusive properties for laser polymerization. Electrical conductivity of
      substrate and its permeability in liquids are promising for bio- and
      electroplating applications.

PMID- 23546074
TI  - Experimental demonstration of self-aligned InP/InGaAsP polarization converter for
      polarization multiplexed photonic integrated circuits.
AB  - Highly efficient, low-loss, and compact InP/InGaAsP polarization converter based
      on a half-ridge waveguide structure is fabricated and demonstrated
      experimentally. The device is fabricated by a simple self-aligned process and
      integrated with a ridge InP waveguide. Using a 150-MUm-long device, we obtain the
      mode conversion of more than 96% and the on-chip loss of less than 1.0 dB over
      the broad wavelength range from 1510 to 1575 nm. The experimental results are
      explained quantitatively using the full-vector eigenmode calculation, which also
      reveals large fabrication tolerance of the demonstrated device.

PMID- 23546076
TI  - Full field model for interleave-chirped arrayed waveguide gratings.
AB  - In this paper, a theoretical model for an Interleave-Chirped Arrayed Waveguide
      Grating (IC-AWG) is presented. The model describes the operation of the device by
      means of a field (amplitude and phase) transfer response. The validation of the
      model is accomplished by means of simulations, using parameters from previously
      fabricated devices. A novel design procedure is derived from the model, and it is
      later on employed to demonstrate the design of colorless universal IC-AWGs. The
      model can be readily applied to the analysis and design of future multi
      wavelength optical coherent communications receivers and optical waveform
      analyzers.

PMID- 23546075
TI  - Dynamic selective etching: a facile route to parabolic optical fiber nano-probe.
AB  - A dynamic etching approach is proposed through the appropriate variation of
      etchant composition ratio during the etching process, resulting in the parabolic
      shape of optical fiber nano-probe with a favorable changing of cone angle. The
      probe formation mechanism is thoroughly analyzed to illustrate the
      controllability and simplicity of this method. Optical properties of as-made
      probes are simulated and experimentally characterized and compared with the
      linear shape probes of different cone angles. It shows that the parabolic shape
      probes are superior to the linear shape ones with respect to the transmission
      efficiency and light focusing capability.

PMID- 23546077
TI  - Design of broadband and high-output power uni-traveling-carrier photodiodes.
AB  - In this paper, physically-based simulations are carried out to investigate and
      design broadband and high-output power uni-traveling carrier (UTC) photodiodes.
      The physical model is first verified by comparison to experimentally measured
      results. The graded-bandgap structure, which can induce potential gradient, is
      considered to be used in the absorption layers. It is shown that the electric
      field in the absorption layer is increased by the gradient, thus the performance
      of bandwidth and saturation current is improved by 36.6% and 40% respectively for
      our considered photodiode. Moreover, a modified graded-bandgap structure is
      proposed to further increase the electric field, and an additional 9.5%
      improvement in bandwidth is achieved. The final proposed UTC-PD structures will
      result in 399-GHz bandwidth and 49-mA DC saturation current.

PMID- 23546078
TI  - Demonstration of focus-tunable diffractive Moire-lenses.
AB  - In an earlier publication [Appl. Opt. 47, 3722 (2008)] we suggested an adaptive
      optical lens, which consists of two cascaded diffractive optical elements (DOEs).
      Due to the Moire-effect the combined optical element acts as a Fresnel zone lens
      with a refractive power that can be continuously adjusted by a mutual rotation of
      the two stacked DOEs. Here we present an experimental realization of this
      concept. Four designs of these Moire-DOEs (MDOEs) were fabricated in thin (0.7
      mm) glass slides by lithography and subsequent etching. Each element was realized
      as a 16 phase level DOE designed for 633 nm illumination. Our experimental
      investigation shows that the Moire-lenses have a broad adjustable refractive
      power range with a high efficiency, which allows one to use them for flexible
      beam steering and for imaging applications.

PMID- 23546079
TI  - Submicron optical waveguides and microring resonators fabricated by selective
      oxidation of tantalum.
AB  - Submicron tantalum pentoxide ridge and channel optical waveguides and microring
      resonators are demonstrated on silicon substrates by selective oxidation of the
      refractory metal, tantalum. The novel method eliminates the surface roughness
      problem normally introduced during dry etching of waveguide sidewalls and also
      simplifies fabrication of directional couplers. It is shown that the measured
      propagation loss is independent of the waveguide structure and thereby limited by
      the material loss of tantalum pentoxide in waveguides core regions. The achieved
      microring resonators have cross-sectional dimensions of ~600 nm * ~500 nm,
      diameters as small as 80 um with a quality, Q, factor of 4.5 * 10(4), and a
      finesse of 120.

PMID- 23546080
TI  - Cryogenic, high power, near diffraction limited, Yb:YAG slab laser.
AB  - A cryogenic slab laser that is suitable for scaling to high power, while taking
      full advantage of the improved thermo-optical and thermo-mechanical properties of
      Yb:YAG at cryogenic temperatures is described. The laser uses a conduction
      cooled, end pumped, zigzag slab geometry resulting in a near diffraction limited,
      robust, power scalable design. The design and the initial characterization of the
      laser up to 200W are presented.

PMID- 23546082
TI  - Detailed analysis of the longitudinal acousto-optical resonances in a fiber Bragg
      modulator.
AB  - The interaction frequencies between longitudinal acoustic waves and fiber Bragg
      grating are numerically and experimentally assessed. Since the grating modulation
      depends on the acoustic drive, the combined analysis provides a more efficient
      operation. In this paper, 3-D finite element and transfer matrix methods allow
      investigating the electrical, mechanical and optical resonances of an acousto
      optical device. The frequency response allows locating the resonances and
      characterizing their mechanical displacements. Measurements of the grating
      response under resonant excitation are compared to simulated results. A smaller
      than <1.5% average difference between simulated-measured resonances indicates
      that the method is useful for the design and characterization of optical
      modulators.

PMID- 23546081
TI  - Cylindrical Bragg mirrors on leg segments of the male Bolivian blueleg tarantula
      Pamphobeteus antinous (Theraphosidae).
AB  - The large male tarantula Pamphobeteus antinous is easily recognized at the
      presence of blue-violet iridescent bristles on some of the segments of its legs
      and pedipalps. The optical properties of these colored appendages have been
      measured and the internal geometrical structure of the bristles have been
      investigated. The coloration is shown to be caused by a curved coaxial multilayer
      which acts as a "cylindrical Bragg mirror".

PMID- 23546083
TI  - All-optical computation system for solving differential equations based on
      optical intensity differentiator.
AB  - We propose and experimentally demonstrate an all-optical differentiator-based
      computation system used for solving constant-coefficient first-order linear
      ordinary differential equations. It consists of an all-optical intensity
      differentiator and a wavelength converter, both based on a semiconductor optical
      amplifier (SOA) and an optical filter (OF). The equation is solved for various
      values of the constant-coefficient and two considered input waveforms, namely,
      super-Gaussian and Gaussian signals. An excellent agreement between the numerical
      simulation and the experimental results is obtained.

PMID- 23546084
TI  - Compact, flexible and versatile photonic differentiator using silicon Mach
      Zehnder interferometers.
AB  - We propose and experimentally demonstrate the flexibility and versatility of
      photonic differentiators using a silicon-based Mach-Zehnder Interferometer (MZI)
      structure. Two differentiation schemes are investigated. In the first scheme, we
      demonstrate high-order photonic field differentiators using on-chip cascaded
      MZIs, including first-, second-, and third-order differentiators. For single
      Gaussian optical pulse injection, the average deviations of all differentiators
      are less than 6.5%. In the second scheme, we demonstrate multifunctional
      differentiators, including intensity differentiator and field differentiator,
      using an on-chip single MZI structure. These different differentiator forms rely
      on the relative shift between the probe wavelength and the MZI resonant notch.
      Our schemes show the advantages of compact footprint, flexible functions and
      versatile differentiation forms. For example, high order field differentiators
      can be used to generate complex temporal waveforms, such as high order Hermite
      Gaussian waveforms. And intensity differentiators are useful for ultra-wideband
      pulse generation.

PMID- 23546085
TI  - Analytical description of subwavelength plasmonic MIM resonators and of their
      combination.
AB  - We show that a periodic array of metal-insulator-metal resonators can be
      described as a high refractive index metamaterial. This approach permits to
      obtain analytically the optical properties of the structure and thus to establish
      conception rules on the quality factor or on total absorption. Furthermore, we
      extend this formalism to the combination of two independent resonators.

PMID- 23546086
TI  - Wavelength independent multimode interference coupler.
AB  - We propose an ultra-broadband multimode interference (MMI) coupler with a
      wavelength range exceeding the O, E, S, C, L and U optical communication bands.
      For the first time, the dispersion property of the MMI section is engineered
      using a subwavelength grating structure to mitigate wavelength dependence of the
      device. We present a 2 * 2 MMI design with a bandwidth of 450nm, an almost
      fivefold enhancement compared to conventional designs, maintaining insertion
      loss, power imbalance and MMI phase deviation below 1dB, 0.6dB and 3 degrees ,
      respectively. The design is performed using an in-house tool based on the 2D
      Fourier Eigenmode Expansion Method (F-EEM) and verified with a 3D Finite
      Difference Time Domain (FDTD) simulator.

PMID- 23546087
TI  - Terahertz surface plasmon polaritons on a semiconductor surface structured with
      periodic V-grooves.
AB  - We demonstrate propagation of terahertz waves confined to a semiconductor surface
      that is periodically corrugated with V-shaped grooves. A one-dimensional array of
      V-grooves is fabricated on a highly-doped silicon surface, using anisotropic wet
      etching of crystalline silicon, thereby forming a plasmonic waveguide. Terahertz
      time domain spectroscopy is used to characterize the propagation of waves near
      the corrugated surface. We observe that the grating structure creates resonant
      modes that are confined near the surface. The degree of confinement and frequency
      of the resonant mode is found to be related to the pitch and depth of the V
      grooves. The surface modes are confirmed through both numerical simulations and
      experimental measurements. Not only does the V-groove geometry represent a new
      and largely unexplored structure for supporting surface waves, but it also
      enables the practical fabrication of terahertz waveguides directly on
      semiconductor surfaces, without relying on reactive-ion etching or electroplating
      of sub-millimeter metallic surfaces.

PMID- 23546088
TI  - Numerical and experimental validation of a three-dimensional combustion
      diagnostic based on tomographic chemiluminescence.
AB  - Three-dimensional (3D) measurements are highly desirable both for fundamental
      combustion research and practical monitoring and control of combustion systems.
      This work discusses a 3D diagnostic based on tomographic chemiluminescence (TC)
      to address this measurement need. The major contributions of this work are
      threefold. First, a hybrid algorithm is developed to solve the 3D TC problem. The
      algorithm was demonstrated in extensive tests, both numerical and experimental,
      to yield 3D reconstruction with high fidelity. Second, an experimental approach
      was designed to enable quantifiable metrics for examining key aspects of the 3D
      TC technique, including its spatial resolution and reconstruction accuracy.
      Third, based on the reconstruction algorithm and experimental results, we
      investigated the effects of the view orientations. The results suggested that for
      an unknown flame, it is better to use projections measured from random
      orientations than restricted orientations (e.g., coplanar orientations). These
      findings are expected to provide insights to the fundamental capabilities of the
      TC technique, and also to facilitate its practical application.

PMID- 23546089
TI  - Opto-thermal analysis of a lightweighted mirror for solar telescope.
AB  - In this paper, an opto-thermal analysis of a moderately heated lightweighted
      solar telescope mirror is carried out using 3D finite element analysis (FEA). A
      physically realistic heat transfer model is developed to account for the
      radiative heating and energy exchange of the mirror with surroundings. The
      numerical simulations show the non-uniform temperature distribution and
      associated thermo-elastic distortions of the mirror blank clearly mimicking the
      underlying discrete geometry of the lightweighted substrate. The computed
      mechanical deformation data is analyzed with surface polynomials and the optical
      quality of the mirror is evaluated with the help of a ray-tracing software. The
      thermal print-through distortions are further shown to contribute to optical
      figure changes and mid-spatial frequency errors of the mirror surface. A
      comparative study presented for three commonly used substrate materials, namely,
      Zerodur, Pyrex and Silicon Carbide (SiC) is relevant to vast area of large optics
      requirements in ground and space applications.

PMID- 23546090
TI  - Mie scattering and optical forces from evanescent fields: a complex-angle
      approach.
AB  - Mie theory is one of the main tools describing scattering of propagating
      electromagnetic waves by spherical particles. Evanescent optical fields are also
      scattered by particles and exert radiation forces which can be used for optical
      near-field manipulations. We show that the Mie theory can be naturally adopted
      for the scattering of evanescent waves via rotation of its standard solutions by
      a complex angle. This offers a simple and powerful tool for calculations of the
      scattered fields and radiation forces. Comparison with other, more cumbersome,
      approaches shows perfect agreement, thereby validating our theory. As examples of
      its application, we calculate angular distributions of the scattered far-field
      irradiance and radiation forces acting on dielectric and conducting particles
      immersed in an evanescent field.

PMID- 23546091
TI  - Simultaneous hyperspectral differential-CARS, TPF and SHG microscopy with a
      single 5 fs Ti:Sa laser.
AB  - We have developed a multimodal multiphoton laser-scanning microscope for cell
      imaging featuring simultaneous acquisition of differential Coherent Antistokes
      Raman Scattering (D-CARS), two-photon fluorescence (TPF) and second harmonic
      generation (SHG) using a single 5 fs Ti:Sa broadband (660-970 nm) laser. The
      spectral and temporal pulse requirements of these modalities were optimized
      independently by splitting the laser spectrum into three parts: TPF/SHG
      excitation (> 900 nm), CARS Pump excitation (< 730 nm), and CARS Stokes
      excitation (730-900 nm). In particular, by applying an equal linear chirp to pump
      and Stokes pulses using glass dispersion we achieved a CARS spectral resolution
      of 10 cm(-1), and acquired CARS images over the 1200-3800 cm(-1) vibrational
      range selected by the time delay between pump and Stokes. A prism pulse
      compressor in the TPF/SHG excitation was used to achieve Fourier limited 30 fs
      pulses at the sample for optimum TPF and SHG. D-CARS was implemented with few
      passive optical elements and enabled simultaneous excitation and detection of two
      vibrational frequencies with a separation adjustable from 20 cm(-1) to 150 cm(-1)
      for selective chemical contrast and background suppression. The
      excitation/detection set-up using beam-scanning was built around a commercial
      inverted microscope stand providing conventional bright-field, differential
      interference contrast and epi-fluorescence for user-friendly characterization of
      biological samples. Examples of CARS hyperspectral images and simultaneous
      acquisition of D-CARS, TPF and SHG images in both forward and epi-direction are
      shown on HeLa cells, stem-cell derived human adipocytes and mouse tissues.

PMID- 23546092
TI  - Experimental study of dispersion characteristics for a series of microstructured
      fibers for customized supercontinuum generation.
AB  - We demonstrate an experimental study of the chromatic dispersion properties for a
      series of microstructured fibers (MSFs) dedicated for a supercontinuum
      generation. With white-light interferometry application we analyze experimentally
      how the small variations of structural parameters, i.e. an air-hole diameter and
      a lattice constant, influence dispersion characteristics in different groups of
      MSFs. Our study provides useful information on how to design the fiber which is
      less sensitive to the fabrication imperfections. Moreover those investigations
      are the initial step to the development of the customized or tunable
      supercontinuum light sources based on MSFs with slightly changed structural
      parameters which can generate light with a different spectrum range, adapted to a
      proper application.

PMID- 23546093
TI  - Enhanced performance of InGaN/GaN based solar cells with an In(0.05)Ga(0.95)N
      ultra-thin inserting layer between GaN barrier and In(0.2)Ga(0.8)N well.
AB  - The effect of ultra-thin inserting layer (UIL) on the photovoltaic performances
      of InGaN/GaN solar cells is investigated. With UIL implemented, the open-circuit
      voltage was increased from 1.4 V to 1.7 V, short-circuit current density was
      increased by 65% and external quantum efficiency was increased by 59%, compared
      to its counterparts at room temperature under 1-sun AM1.5G illumination. The
      improvements in electrical and photovoltaic properties are mainly attributed to
      the UIL which can boost the crystal quality and alleviate strain. Moreover, it
      can act as a transition layer for higher indium incorporation and an effective
      light sub-absorption layer in multiple quantum wells.

PMID- 23546094
TI  - An improvement of light extraction efficiency for GaN-based light emitting diodes
      by selective etched nanorods in periodic microholes.
AB  - We have demonstrated the enhancement of a GaN-based light emitting diode (LED) by
      means of a selective etching technique. A conventional LED structure was
      periodically etched, to form periodic microholes. It showed an improvement of the
      light extraction efficiency (LEE) of approximately 15%, compared to that of a
      conventional LED. Furthermore, nano-sized rods inside the microholes were
      randomly formed by using a powder mask, resulting in an LEE of 43%. From the
      result of confocal scanning electroluminescence measurement, the light emission
      arises mainly from the vicinity of the nanorods in the periodic microholes.
      Therefore, we found that nanorods randomly distributed in periodic microholes in
      a LED structure play a significant role in the reduction of total internal
      reflection, by acting as photon wave-guides and scattering centers. This method
      would be valuable for the fabrication of high efficiency GaN-based LED, in terms
      of technical simplification and cost.

PMID- 23546096
TI  - Surface localized polymer aligned liquid crystal lens.
AB  - The surface localized polymer alignment (SLPA) method allows complete control of
      the polar pretilt angle as a function of position in liquid crystal devices. In
      this work, a liquid crystal (LC) cylindrical lens is fabricated by the SLPA
      method. The focal length of the LC lens is set by the polymerization conditions,
      and can be varied by a non-segmented electrode. The LC lens does not require a
      shaped substrate, or complicated electrode patterns, to achieve a desired
      parabolic phase profile. Therefore, both fabrication and driving process are
      relatively simple.

PMID- 23546097
TI  - Dual-coil magnetomotive optical coherence tomography for contrast enhancement in
      liquids.
AB  - Magnetomotive optical coherence tomography (MM-OCT) is a functional extension of
      OCT which utilizes magnetically responsive materials that are modulated by an
      external magnetic field for contrast enhancement and for elastography to assess
      the structural and viscoelastic properties of the surrounding tissues.
      Traditionally, magnetomotive contrast relies on the interaction between the
      displacement of magnetic particles induced by an external magnetic field and the
      micro-environmental restoring (elastic) force acting on the particles. When the
      restoring force from a sample containing magnetic particles is weak or non
      existent, the MM-OCT signal-to-noise ratio (SNR) can degrade significantly. We
      have developed a novel solenoid configuration to enable MM-OCT imaging in samples
      that do not have an elastic restoring force, such as liquids. This coil
      configuration may potentially enable real-time MM-OCT imaging.

PMID- 23546098
TI  - A high efficiency architecture for cascaded Raman fiber lasers.
AB  - We demonstrate a new high efficiency architecture for cascaded Raman fiber lasers
      based on a single pass cascaded amplifier configuration. Conversion is seeded at
      all intermediate Stokes wavelengths using a multi-wavelength seed source. A lower
      power Raman laser based on the conventional cascaded Raman resonator architecture
      provides a convenient seed source providing all the necessary wavelengths
      simultaneously. In this work we demonstrate a 1480nm laser pumped by an 1117nm Yb
      doped fiber laser with maximum output power of 204W and conversion efficiency of
      65% (quantum-limited efficiency is ~75%). We believe both the output power and
      conversion efficiency (relative to quantum-limited efficiency) are the highest
      reported for cascaded Raman fiber lasers.

PMID- 23546099
TI  - Wavelength switchable high-power diode-side-pumped rod Tm:YAG Laser around 2um.
AB  - We report a high-power diode-side-pumped rod Tm:YAG laser operated at either 2.07
      or 2.02 um depending on the transmission of pumped output coupler. The laser
      yields 115W of continuous-wave output power at 2.07 um with 5% output coupling,
      which is the highest output power for all solid-state 2.07 MUm cw rod Tm:YAG
      laser reported so far. With an output coupler of 10% transmission, the center
      wavelength of the laser is switched to 2.02 MUm with an output power of 77.1 W.
      This is the first observation of high-power wavelength switchable diode-side
      pumped rod Tm:YAG laser around 2 um.

PMID- 23546100
TI  - Strain induced bandgap and refractive index variation of silicon.
AB  - We present a study of the influence of high strain on the bandgap and the
      refractive index of silicon. The results of photoluminescence show that with the
      strain applied, the silicon bandgap can be adjusted to 0.84 eV and the refractive
      index of silicon increases significantly. 1.4% change of refractive index of
      silicon was observed. The strain-induced bandgap shrinkage and absorption
      coefficient change of silicon are considered as the main cause of the significant
      refractive index change. The present work indicates that the application of
      strain is promising to control the refractive index of silicon in devices so that
      applications such as compensation of thermal effect in optical devices can be
      achieved.

PMID- 23546101
TI  - Time-frequency analysis of long fiber Bragg gratings with low reflectivity.
AB  - A new technique to investigate the spatial distribution of the reflection
      spectrum along fabricated long weak fiber Bragg gratings (FBG) is experimentally
      demonstrated, together with its potential applications for distributed fiber
      sensing and broadband signal processing. A short pulsed coherent light signal is
      launched into a FBG and the signal frequency is scanned through the FBG
      reflection spectrum. When the pulse duration is set much shorter than the transit
      time through the grating a time-resolved reflected signal can be obtained for
      each signal frequency. It informs about the distribution of the refractive index
      periodic perturbation along the entire FBG length, hence the uniformity or
      frequency chirp information of the fabricated FBG. This technique has been
      implemented to demonstrate a distributed temperature sensing system with high
      spatial resolution and to also realize a robust all-fiber tunable delay line for
      broadband signals.

PMID- 23546102
TI  - Method to improve the noise figure and saturation power in multi-contact
      semiconductor optical amplifiers: simulation and experiment.
AB  - The consequences of tailoring the longitudinal carrier density along the active
      layer of a multi-contact bulk semiconductor optical amplifier (SOA) are
      investigated using a rate equation model. It is shown that both the noise figure
      and output power saturation can be optimized for a fixed total injected bias
      current. The simulation results are validated by comparison with experiment using
      a multi-contact SOA. The inter-contact resistance is increased using a focused
      ion beam in order to optimize the carrier density control. A chip noise figure of
      3.8 dB and a saturation output power of 9 dBm are measured experimentally for a
      total bias current of 150 mA.

PMID- 23546103
TI  - Plasmonically enhanced hot electron based photovoltaic device.
AB  - Hot electron photovoltaics is emerging as a candidate for low cost and ultra thin
      solar cells. Plasmonic means can be utilized to significantly boost device
      efficiency. We separately form the tunneling metal-insulator-metal (MIM) junction
      for electron collection and the plasmon exciting MIM structure on top of each
      other, which provides high flexibility in plasmonic design and tunneling MIM
      design separately. We demonstrate close to one order of magnitude enhancement in
      the short circuit current at the resonance wavelengths.

PMID- 23546104
TI  - Investigation of a planar optical waveguide in 2D PPLN using helium implantation
      technique.
AB  - In this work, we report the investigation of a planar waveguide in a 2D
      periodically-poled lithium niobate (PPLN). The waveguide is fabricated by helium
      (He(+)) implantation at 2 MeV and a fluence of 1.5 x 10(16) ions/cm(2). Second
      harmonic generation (SHG) at 532 nm using a Q-switched laser and a CW laser diode
      at 1064 nm, was measured as a function of angular distribution and temperature.
      The experimental results show higher gain in SHG conversion efficiency in the
      waveguide than in the bulk 2D PPLN. In particular, SHGs from 2D reciprocal
      lattice vectors (RLV) are observed and studied.

PMID- 23546105
TI  - Probing scattering mechanisms with symmetric quantum cascade lasers.
AB  - A characteristic feature of quantum cascade lasers is their unipolar carrier
      transport. We exploit this feature and realize nominally symmetric active regions
      for terahertz quantum cascade lasers, which should yield equal performance with
      either bias polarity. However, symmetric devices exhibit a strongly bias polarity
      dependent performance due to growth direction asymmetries, making them an ideal
      tool to study the related scattering mechanisms. In the case of an InGaAs/GaAsSb
      heterostructure, the pronounced interface asymmetry leads to a significantly
      better performance with negative bias polarity and can even lead to
      unidirectionally working devices, although the nominal band structure is
      symmetric. The results are a direct experimental proof that interface roughness
      scattering has a major impact on transport/lasing performance.

PMID- 23546106
TI  - Robust 9-QAM digital recovery for spectrum shaped coherent QPSK signal.
AB  - We propose 9-ary quadrature amplitude modulation (9-QAM) data recovery for
      polarization multiplexing-quadrature phase shift keying (PM-QPSK) signal in
      presence of strong filtering to approach Nyquist bandwidth. The decision-directed
      least radius distance (DD-LRD) algorithm for blind equalization is used for 9-QAM
      recovery and intersymbol interference (ISI) compression. It shows the robustness
      under strong filtering to recover 9-QAM signal rather than QPSK. We demonstrate
      112 Gb/s spectrum shaped PM-QPSK signal by wavelength selective switch (WSS) in a
      25-GHz channel spacing Nyquist wavelength division multiplexing (NWDM). The final
      equalized signal is detected by maximum likelihood sequence decision (MLSD) for
      data bit-error-ratio (BER) measurement. Optical signal-to-noise ratio (OSNR)
      tolerance is improved by 0.5 dB at a BER of 1x10(-3) compared to constant modulus
      algorithm (CMA) plus post-filter algorithm.

PMID- 23546107
TI  - Simultaneous multiple view high resolution surface geometry acquisition using
      structured light and mirrors.
AB  - Knowledge of the surface geometry of an imaging subject is important in many
      applications. This information can be obtained via a number of different
      techniques, including time of flight imaging, photogrammetry, and fringe
      projection profilometry. Existing systems may have restrictions on instrument
      geometry, require expensive optics, or require moving parts in order to image the
      full surface of the subject. An inexpensive generalised fringe projection
      profilometry system is proposed that can account for arbitrarily placed
      components and use mirrors to expand the field of view. It simultaneously
      acquires multiple views of an imaging subject, producing a cloud of points that
      lie on its surface, which can then be processed to form a three dimensional
      model. A prototype of this system was integrated into an existing Diffuse Optical
      Tomography and Bioluminescence Tomography small animal imaging system and used to
      image objects including a mouse-shaped plastic phantom, a mouse cadaver, and a
      coin. A surface mesh generated from surface capture data of the mouse-shaped
      plastic phantom was compared with ideal surface points provided by the phantom
      manufacturer, and 50% of points were found to lie within 0.1mm of the surface
      mesh, 82% of points were found to lie within 0.2mm of the surface mesh, and 96%
      of points were found to lie within 0.4mm of the surface mesh.

PMID- 23546108
TI  - ZnO nanorod optical disk photocatalytic reactor for photodegradation of methyl
      orange.
AB  - A low-cost and efficient photocatalytic reactor for environmental treatment and
      green technology was presented. ZnO nanorods firmly growing on polycarbonate
      optical disk substrate are generally perpendicular to the substrate as the
      immobilized photocatalyst of the spinning disk reactor. The photocatalytic
      efficiency and durability of the ZnO nanorods are effectively demonstrated.

PMID- 23546109
TI  - Study of coupling loss on strongly-coupled, ultra compact microring resonators.
AB  - Small-radius microring resonators with large free spectral range (FSR) are of
      great interest for optical communication and optical interconnect applications.
      The resonator loss of a waveguide-coupled ring resonator, if the gap width
      between the microring and the bus waveguide is extremely small, can be
      significantly influenced by the coupling loss which corresponds to the microring
      operated in a strong coupling regime. This effect is particularly prominent for
      small radius microrings. We have studied the coupling loss with respect to the
      gap width on a waveguide-coupled microring both experimentally and theoretically,
      using two-dimensional (2D) finite difference time domain (FDTD) and effective
      index method (EIM).The coupling loss was confirmed by measuring transmission
      spectra of Si microring filters fabricated on silicon-on-insulator (SOI) wafers.
      Our experimental data show that the ring loss increases rapidly as the coupling
      gap decreases to less than 200 nm. The measured results show that the ring loss
      of a silicon microring with a radius of 2.75 MUm is around 0.01382
      dB/circumference as the gap width is greater than 325 nm, referred to as the
      intrinsic ring loss. However, for a smaller gap of 150 nm, the loss of the
      microring increases to 0.07084dB/circumference. The added ring loss is attributed
      to the coupling loss at small coupling gap for small radius ring.

PMID- 23546110
TI  - Optomechanical and photothermal interactions in suspended photonic crystal
      membranes.
AB  - We present here an optomechanical system fabricated with novel stress management
      techniques that allow us to suspend an ultrathin defect-free silicon photonic
      crystal membrane above a Silicon-on-Insulator (SOI) substrate with a gap that is
      tunable to below 200 nm. Our devices are able to generate strong attractive and
      repulsive optical forces over a large surface area with simple in- and out-
      coupling and feature the strongest repulsive optomechanical coupling in any
      geometry to date (gOM/2pi ~65 GHz/nm). The interplay between the optomechanical
      and photo-thermal-mechanical dynamics is explored, and the latter is used to
      achieve cooling and amplification of the mechanical mode, demonstrating that our
      platform is well-suited for potential applications in low-power mass, force, and
      refractive-index sensing as well as optomechanical accelerometry.

PMID- 23546111
TI  - RF up/down-conversion based on optically injection-locked VCSEL.
AB  - All-optical radio frequency conversion is proposed by directly modulated
      optically injection-locked vertical-cavity surface-emitting lasers. The
      enhancement effect of second order products of RF signals by OIL technique is
      analyzed based on reflection-mode OIL model. Simulation results show that high
      injection ratio and large wavelength detuning of OIL condition lead to a high RF
      conversion gain. Compared with free running condition, more than 20 dB RF
      conversion gain enhancement is achieved in the simulation. The experimental
      results of the RF conversion gain improvement (+ 18 dB) by OIL show excellent
      agreement with our simulation results. The spurious free dynamic range
      improvement (+ 15 dB) of conversion signals by OIL is also experimentally
      demonstrated.

PMID- 23546112
TI  - Improvement and formation of UV-induced damage on LBO crystal surface during long
      term high-power third-harmonic generation.
AB  - We demonstrate the improvement and formation of UV-induced damage on LBO crystal
      output surface during long-term (130 h) high-power (20 W) high-repetition-rate
      (80 kHz) third-harmonic generation. The output surface was super-polished (RMS
      surface roughness <0.6 nm) to sub-nanometer scale super smooth roughness. The
      surface lifetime has been improved more than 20-fold compared with the as
      polished ones (RMS surface roughness 4.0~8.0 nm). The damage could be attributed
      to the consequence of thermal effects resulted from impurity absorptions.
      Simultaneously, it was verified that the impurities originated in part from the
      UV-induced deposition.

PMID- 23546113
TI  - Demonstration of a plenoptic microscope based on laser optical feedback imaging.
AB  - A new kind of plenoptic imaging system based on Laser Optical Feedback Imaging
      (LOFI) is presented and is compared to another previously existing device based
      on microlens array. Improved photometric performances, resolution and depth of
      field are obtained at the price of a slow point by point scanning. Main
      properties of plenoptic microscopes such as numerical refocusing on any curved
      surface or aberrations compensation are both theoretically and experimentally
      demonstrated with a LOFI-based device.

PMID- 23546114
TI  - Broadband directional coupling in aluminum nitride nanophotonic circuits.
AB  - Aluminum nitride (AlN)-on-insulator has emerged as a promising platform for the
      realization of linear and non-linear integrated photonic circuits. In order to
      efficiently route optical signals on-chip, precise control over the interaction
      and polarization of evanescently coupled waveguide modes is required. Here we
      employ nanophotonic AlN waveguides to realize directional couplers with a broad
      coupling bandwidth and low insertion loss. We achieve uniform splitting of
      incoming modes, confirmed by high extinction-ratio exceeding 33dB in integrated
      Mach-Zehnder Interferometers. Optimized three-waveguide couplers furthermore
      allow for extending the coupling bandwidth over traditional side-coupled devices
      by almost an order of magnitude, with variable splitting ratio. Our work
      illustrates the potential of AlN circuits for coupled waveguide optics, DWDM
      applications and integrated polarization diversity schemes.

PMID- 23546115
TI  - Blind-deconvolution optical-resolution photoacoustic microscopy in vivo.
AB  - Optical-resolution photoacoustic microscopy (OR-PAM) is becoming a vital tool for
      studying the microcirculation system in vivo. By increasing the numerical
      aperture of optical focusing, the lateral resolution of OR-PAM can be improved;
      however, the depth of focus and thus the imaging range will be sacrificed
      correspondingly. In this work, we report our development of blind-deconvolution
      optical-resolution photoacoustic microscopy (BD-PAM) that can provide a lateral
      resolution ~2-fold finer than that of conventional OR-PAM (3.04 vs. 5.78MUm),
      without physically increasing the system's numerical aperture. The improvement
      achieved with BD-PAM is demonstrated by imaging graphene nanoparticles and the
      microvasculature of mice ears in vivo. Our results suggest that BD-PAM may become
      a valuable tool for many biomedical applications that require both fine spatial
      resolution and extended depth of focus.

PMID- 23546116
TI  - Super-thin Mikaelian's lens of small index as a beam compressor with an extremely
      high compression ratio.
AB  - Based on a focusing Mikaelian's lens with small refraction index (0<n<<1), an
      optical device is designed as a super-thin optical beam compressor (e.g.,
      thickness = 3lambda0) with an extremely high beam compression ratio (more than
      19:1). This device can also be used as a beam collimator or a cylindrical-to
      plane wave convertor with a much higher transmissivity than a zero-index
      metamaterial slab. The output beam shows good directionality in both near field
      and far field. A metamaterial structure is also designed to realize this device
      and verify its performance with finite element method (FEM).

PMID- 23546117
TI  - Effect of non-vacuum thermal annealing on high indium content InGaN films
      deposited by pulsed laser deposition.
AB  - InGaN films with 33% and 60% indium contents were deposited by pulsed laser
      deposition (PLD) at a low growth temperature of 300  degrees C. The films were
      then annealed at 500-800  degrees C in the non-vacuum furnace for 15 min with an
      addition of N(2) atmosphere. X-ray diffraction results indicate that the indium
      contents in these two films were raised to 41% and 63%, respectively, after
      annealing in furnace. In(2)O(3) phase was formed on InGaN surface during the
      annealing process, which can be clearly observed by the measurements of auger
      electron spectroscopy, transmission electron microscopy and x-ray photoelectron
      spectroscopy. Due to the obstruction of indium out-diffusion by forming In(2)O(3)
      on surface, it leads to the efficient increment in indium content of InGaN layer.
      In addition, the surface roughness was greatly improved by removing In(2)O(3)
      with the etching treatment in HCl solution. Micro-photoluminescence measurement
      was performed to analyze the emission property of InGaN layer. For the as-grown
      InGaN with 33% indium content, the emission wavelength was gradually shifted from
      552 to 618 nm with increasing the annealing temperature to 800  degrees C. It
      reveals the InGaN films have high potential in optoelectronic applications.

PMID- 23546118
TI  - Design of cylindrical vector beams based on the rotating Glan polarizing prism.
AB  - Recently the cylindrically polarized beams have been gained highly attention in
      the fields of particle manipulation, material processing, nanoscale imaging, etc.
      So the methods to create the cylindrically polarized beams become more important.
      Here, based on the principle of the Glan polarizing prism, we design two types of
      the structures of the cylindrical polarization analyzer that can convert directly
      a linearly or circularly polarized beam into various cylindrical vector beams.
      The key optical element in the cylindrical polarization analyzer is the
      cylindrical polarizing prism with unique structure. We demonstrate the operating
      principle and the feasibility of the fabrication of the cylindrical polarization
      analyzer in detail. Analyses show that the cylindrical polarization analyzer
      designed by us not only have novel structures and excellent characteristics, such
      as the compact and stabile structures, high extinction ratio, high polarization
      purity, no requirements on the mode and the wavelength of the incident light
      (only for the first type), not changing the intensity distribution of the
      incident light, and easily integrated into the optical systems, but also is easy
      to be fabricated, especially for the second type.

PMID- 23546119
TI  - Nonlinearity mitigation for high-speed optical OFDM transmitters using digital
      pre-distortion.
AB  - Optical orthogonal frequency-division multiplexing (OOFDM) signal is sensitive to
      nonlinear distortions induced by optical modulators. We propose and
      experimentally demonstrate a digital pre-distortion (DPD) algorithm to linearize
      the optical modulators including electro-absorption modulated lasers (EML) and
      Mach-Zehnder modulators (MZM) used in high-speed OOFDM transmitters. By using an
      adaptive DPD algorithm with a learning structure, the inverse transfer function
      of a modulator, which is based on a polynomial model, has been obtained. In the
      experiment, the performance improvements with and without considering the memory
      effects of the DPD model are illustrated. The two typical kinds of high-speed
      OOFDM signals with a bit rate up to 30-Gb/s have been implemented experimentally.
      The results show that the nonlinear distortion induced by optical modulators can
      be compensated by using the DPD algorithm to substantially improve the optical
      modulation index.

PMID- 23546120
TI  - Differential interferometric particle tracking on the subnanometer- and
      submillisecond-scale.
AB  - We describe an interferometric method to measure the movement of a subwavelength
      probe particle relative to an immobilized reference particle with high spatial
      (Deltax = 0.9nm) and temporal (Deltat = 200MUs) resolution. The differential
      method eliminates microscope stage drift. An upright microscope is equipped with
      laser dark field illumination (lambda(0) = 532nm, P(0) = 30mW) and a compact
      modified Mach-Zehnder interferometer is mounted on the camera exit of the
      microscope, where the beams of scattered light of both particles are combined.
      The resulting interferograms provide in two channels subnanometer information
      about the motion of the probe particle relative to the reference particle. The
      interferograms are probed with two avalanche photodiodes. We applied this method
      to measuring the movement of kinesin along microtubules and were able to resolve
      the generic 8-nm steps at high ATP concentrations without external forces.

PMID- 23546121
TI  - Simulation of modulation transfer function using a rendering method.
AB  - We propose a novel simulation method based on rendering to evaluate the
      modulation transfer function (MTF) of optical imaging systems. The new simulation
      method corresponds to an experimental measurement of the MTF using imaging
      resolution test charts, and therefore allows an analysis of the resolving power
      of shift-variant optical systems that are difficult to evaluate with conventional
      methods based on the point spread function (PSF). Furthermore, the effects of
      stray light, such as from reflection or scattering, on the imaging performance
      can be analyzed. In contrast to methods based on illumination optics using Monte
      Carlo methods, the proposed method calculates the intensities on an image surface
      with rendering techniques used in three-dimensional computer graphics (3D CG),
      which results in calculations that are faster and have a higher precision. The
      proposed method is highly effective in analyzing the MTF of optical imaging
      systems through simulations.

PMID- 23546122
TI  - Comparison of single distance phase retrieval algorithms by considering different
      object composition and the effect of statistical and structural noise.
AB  - Phase retrieval is a technique for extracting quantitative phase information from
      X-ray propagation-based phase-contrast tomography (PPCT). In this paper, the
      performance of different single distance phase retrieval algorithms will be
      investigated. The algorithms are herein called phase-attenuation duality Born
      Algorithm (PAD-BA), phase-attenuation duality Rytov Algorithm (PAD-RA), phase
      attenuation duality Modified Bronnikov Algorithm (PAD-MBA), phase-attenuation
      duality Paganin algorithm (PAD-PA) and phase-attenuation duality Wu Algorithm
      (PAD-WA), respectively. They are all based on phase-attenuation duality property
      and on weak absorption of the sample and they employ only a single distance PPCT
      data. In this paper, they are investigated via simulated noise-free PPCT data
      considering the fulfillment of PAD property and weakly absorbing conditions, and
      with experimental PPCT data of a mixture sample containing absorbing and weakly
      absorbing materials, and of a polymer sample considering different degrees of
      statistical and structural noise. The simulation shows all algorithms can
      quantitatively reconstruct the 3D refractive index of a quasi-homogeneous weakly
      absorbing object from noise-free PPCT data. When the weakly absorbing condition
      is violated, the PAD-RA and PAD-PA/WA obtain better result than PAD-BA and PAD
      MBA that are shown in both simulation and mixture sample results. When
      considering the statistical noise, the contrast-to-noise ratio values decreases
      as the photon number is reduced. The structural noise study shows that the result
      is progressively corrupted by ring-like artifacts with the increase of structural
      noise (i.e. phantom thickness). The PAD-RA and PAD-PA/WA gain better density
      resolution than the PAD-BA and PAD-MBA in both statistical and structural noise
      study.

PMID- 23546123
TI  - Design and laboratory demonstration of an achromatic vector vortex coronagraph.
AB  - A vector vortex coronagraph (VVC) is one of promising means for imaging extremely
      faint objects around bright stars such as exoplanets. We present a design of an
      achromatic VVC, in which an axially-symmetric half-wave plate (AHP) is placed
      between crossed polarization filters (circular polarizer and analyzer). The
      circular polarizer and the analyzer are both composed of a polarizer and a
      quarter-wave plate (QWP). We demonstrate, via Jones calculus and Fourier
      analysis, that the achromatic stellar elimination can theoretically be realized
      by optimal polarization filters, even when chromatic AHP and QWPs are used. We
      carried out laboratory demonstrations of the designed VVC using a photonic
      crystal AHP. As a result, we observed achromatic coronagraphic performance, a
      light suppression level of 7 * 10(-5), over a wavelength from 543 nm to 633 nm.

PMID- 23546124
TI  - Chemical detection with hyperspectral lidar using dual frequency combs.
AB  - High-resolution spectral lidar measurements using dual frequency combs as a
      source is presented. The technique enables the range-resolved measurement of fine
      spectral features, such as gas absorption lines, provided that a suitable
      scatterer is present in the scene. Measurements of HCN absorption lines at 20
      meters are presented, with a water droplet cloud and a diffusely reflective
      surface as scatterers.

PMID- 23546125
TI  - Disentangling the effects of clustering and multi-exciton emission in second
      order photon correlation experiments.
AB  - In single particle spectroscopy, the degree of observed fluorescence anti
      bunching in a second-order cross correlation experiment is indicative of its bi
      exciton quantum yield and whether or not a particle is well isolated. Advances in
      quantum dot synthesis have produced single particles with bi-exciton quantum
      yields approaching unity. Consequently, this creates uncertainty as to whether a
      particle has a high bi-exciton quantum yield or if it exists as a cluster. We
      report on a time-gated anti-bunching technique capable of determining the
      relative contributions of both multi-exciton emission and clustering effects. In
      this way, we can now unambiguously determine if a particle is single.
      Additionally, this time-gated anti-bunching approach provides an accurate way for
      the determination of bi-exciton lifetime with minimal contribution from higher
      order multi-exciton states.

PMID- 23546126
TI  - Adjustable subwavelength localization in a hybrid plasmonic waveguide.
AB  - The hybrid plasmonic waveguide consists of a high-permittivity dielectric
      nanofiber embedded in a low-permittivity dielectric near a metal surface. This
      architecture is considered as one of the most perspective candidates for long
      range subwavelength guiding. We present qualitative analysis and numerical
      results which reveal advantages of the special waveguide design when dielectric
      constant of the cylinder is greater than the absolute value of the dielectric
      constant of the metal. In this case the arbitrary subwavelength mode size can be
      achieved by controlling the gap width. Our qualitative analysis is based on
      consideration of sandwich-like conductor-gap-dielectric system. The numerical
      solution is obtained by expansion of the hybrid plasmonic mode over single
      cylinder modes and the surface plasmon-polariton modes of the metal screen and
      matching the boundary conditions.

PMID- 23546127
TI  - 90 degrees  polarization rotator with rotation angle independent of substrate
      permittivity and incident angles using a composite chiral metamaterial.
AB  - We propose a more efficient way to obtain much stronger polarization rotatory
      power by constructing a composite chiral metamaterial (CCMM) which is achieved
      via the combination of the cut-wire pairs (CWPs) and a purely chiral metamaterial
      (PCMM) composed of conjugated gammadion resonators. Owing to the strong coupling
      between the CWPs and PCMM, the polarization rotation in our CCMM is more gigantic
      than that of the PCMM. Furthermore, the CCMM proposed in this paper can function
      as a wide-angle 90 degrees  polarization rotator for different substrate
      permittivity without needing to adjust its geometric parameters. Due to the
      unique properties, the CCMM may greatly benefit potential applications including
      designing a tunable 90 degrees -polarization rotator, microwave devices,
      telecommunication, and so on.

PMID- 23546128
TI  - Resonant two-photon absorption and electromagnetically induced transparency in
      open ladder-type atomic system.
AB  - We have experimentally and theoretically studied resonant two-photon absorption
      (TPA) and electromagnetically induced transparency (EIT) in the open ladder-type
      atomic system of the 5S(1/2) (F = 1)-5P(3/2) (F' = 0, 1, 2)-5D(5/2) (F" = 1, 2,
      3) transitions in (87)Rb atoms. As the coupling laser intensity was increased,
      the resonant TPA was transformed to EIT for the 5S(1/2) (F = 1)-5P(3/2) (F' = 2)
      5D(5/2) (F" = 3) transition. The transformation of resonant TPA into EIT was
      numerically calculated for various coupling laser intensities, considering all
      the degenerate magnetic sublevels of the 5S(1/2)-5P(3/2)-5D(5/2) transition. From
      the numerical results, the crossover from TPA to EIT could be understood by the
      decomposition of the spectrum into an EIT component owing to the pure two-photon
      coherence and a TPA component caused by the mixed term.

PMID- 23546129
TI  - Wavelet-based decomposition of high resolution surface plasmon microscopy V(Z)
      curves at visible and near infrared wavelengths.
AB  - Surface plasmon resonance is conventionally conducted in the visible range and,
      during the past decades, it has proved its efficiency in probing molecular scale
      interactions. Here we elaborate on the first implementation of a high resolution
      surface plasmon microscope that operates at near infrared (IR) wavelength for the
      specific purpose of living matter imaging. We analyze the characteristic angular
      and spatial frequencies of plasmon resonance in visible and near IR lights and
      how these combined quantities contribute to the V(Z) response of a scanning
      surface plasmon microscope (SSPM). Using a space-frequency wavelet decomposition,
      we show that the V(Z) response of the SSPM for red (632.8 nm) and near IR (1550
      nm) lights includes the frequential response of plasmon resonance together with
      additional parasitic frequencies induced by the objective pupil. Because the
      objective lens pupil profile is often unknown, this space-frequency decomposition
      turns out to be very useful to decipher the characteristic frequencies of the
      experimental V(Z) curves. Comparing the visible and near IR light responses of
      the SSPM, we show that our objective lens, primarily designed for visible light
      microscopy, is still operating very efficiently in near IR light. Actually,
      despite their loss in resolution, the SSPM images obtained with near IR light
      remain contrasted for a wider range of defocus values from negative to positive Z
      values. We illustrate our theoretical modeling with a preliminary experimental
      application to blood cell imaging.

PMID- 23546130
TI  - A novel transform domain processing based channel estimation method for OFDM
      radio-over-fiber systems.
AB  - In this paper, a transform domain processing (TDP) based channel estimation
      method for orthogonal frequency-division multiplexing (OFDM) Radio-over-Fiber
      (RoF) systems is proposed. Theoretically investigation shows that TDP can greatly
      reduce the number of required training symbols. An 8 x 4.65 Gb/s multi-user OFDM
      RoF system over 40 km fiber link and 60 GHz wireless link is experimentally
      demonstrated utilizing TDP scheme. Compared with conventional time domain
      averaging (TDA) scheme, the overhead can be reduced from several tens of training
      symbols to merely one symbol and the receiver sensitivity has been improved by
      1.8 dB at BER of 3.8 x 10(-3). The calculated BER performance for 8 wireless
      users clearly validates the feasibility of this TDP-based channel estimation
      method.

PMID- 23546131
TI  - Tomographic imaging via spectral encoding of spatial frequency.
AB  - Three-dimensional optical tomographic imaging plays an important role in
      biomedical research and clinical applications. We introduce spectral tomographic
      imaging (STI) via spectral encoding of spatial frequency principle that not only
      has the capability for visualizing the three-dimensional object at sub-micron
      resolution but also providing spatially-resolved quantitative characterization of
      its structure with nanoscale accuracy for any volume of interest within the
      object. The theoretical basis and the proof-of-concept numerical simulations are
      presented to demonstrate the feasibility of spectral tomographic imaging.

PMID- 23546132
TI  - Polarization holograms allow highly efficient generation of complex light beams.
AB  - We report a viable method to generate complex beams, such as the non-diffracting
      Bessel and Weber beams, which relies on the encoding of amplitude information, in
      addition to phase and polarization, using polarization holography. The holograms
      are recorded in polarization sensitive films by the interference of a reference
      plane wave with a tailored complex beam, having orthogonal circular
      polarizations. The high efficiency, the intrinsic achromaticity and the
      simplicity of use of the polarization holograms make them competitive with
      respect to existing methods and attractive for several applications. Theoretical
      analysis, based on the Jones formalism, and experimental results are shown.

PMID- 23546133
TI  - Transient thermal effect, nonlinear refraction and nonlinear absorption
      properties of graphene oxide sheets in dispersion.
AB  - The nonlinear refraction (NLR) properties of graphene oxide (GO) in N, N
      Dimethylformamide (DMF) was studied in nanosecond, picosecond and femtosecond
      time regimes by Z-scan technique. Results show that the dispersion of GO in DMF
      exhibits negative NLR properties in nanosecond time regime, which is mainly
      attributed to transient thermal effect in the dispersion. The dispersion also
      exhibits negative NLR in picosecond and femtosecond time regimes, which are
      arising from sp(2)- hybridized carbon domains and sp(3)- hybridized matrix in GO
      sheets. To illustrate the relations between NLR and nonlinear absorption (NLA),
      NLA properties of the dispersion were also studied in nanosecond, picosecond and
      femtosecond time regimes.

PMID- 23546134
TI  - A continuously tunable multi-tap complex-coefficient microwave photonic filter
      based on a tilted fiber Bragg grating.
AB  - The coupling coefficients of the cladding-mode resonances of a tilted fiber Bragg
      grating (TFBG) are linearly increasing or decreasing in different wavelength
      regions. Based on the Kramers-Kronig relations, when the coupling coefficients
      are linearly increasing, the phase shifts are linearly increasing
      correspondingly. This feature is employed, for the first time, for the
      implementation of a multi-tap continuously tunable microwave photonic filter with
      complex coefficients by using a TFBG. By locating the optical carriers of single
      sideband-modulated signals at the cladding-mode resonances of the TFBG which has
      linearly increasing depths, linearly increasing phase shifts are introduced to
      the optical carriers. By beating the optical carriers with the single sidebands,
      the phase shifts are translated to the microwave signals, and thus complex
      coefficients with the required linearly increasing phase shifts are generated.
      The tunability of the complex coefficients is realized by optically pumping the
      TFBG which is written in an erbium/ytterbium (Er/Yb) co-doped fiber. A proof-of
      concept experiment is performed; a three- and four-tap filter with a frequency
      tunable range of 150 and 120 MHz, respectively, are demonstrated.

PMID- 23546135
TI  - Axial nano-displacement measurement with high resolution and wide range based on
      asymmetrical illumination.
AB  - We propose a novel axial nano-displacement measuring approach. Based on
      asymmetrical illumination, the axial drifts of the sample plane can be measured
      by detecting the position of the centroid of the focal spot. Both CCD and QD are
      used as the detector in the system and two data processing models are designed.
      With a relatively simple and applicable configuration, the proposed system can
      realize a wide measuring range of >4lambdaand a high axial resolution of 2nm.
      Moreover, the presented approach is immune to the influence caused by the energy
      fluctuation of the laser source. Possessing these advantages, this measuring
      method has big potential to be applied in modern engineering and scientific
      researches.

PMID- 23546136
TI  - Interplay between electric and magnetic effect in adiabatic polaritonic systems.
AB  - We report on the possibility of realizing adiabatic compression of polaritonic
      wave on a metallic conical nano-structure through an oscillating electric
      potential (quasi dynamic regime). By comparing this result with an
      electromagnetic wave excitation, we were able to relate the classical lighting
      rod effect to adiabatic compression. Furthermore, we show that while the magnetic
      contribution plays a marginal role in the formation of adiabatic compression, it
      provides a blue shift in the spectral region. In particular, magnetic
      permeability can be used as a free parameter for tuning the polaritonic
      resonances. The peculiar form of adiabatic compression is instead dictated by
      both the source and the metal permittivity. The analysis is performed by starting
      from a simple electrostatic system to end with the complete electromagnetic one
      through intermediate situations such as the quasi-electrostatic and quasi-dynamic
      regimes. Each configuration is defined by a particular set of equations which
      allows to clearly determine the individual role played by the electric and
      magnetic contribution in the generation of adiabatic compression. We notice that
      these findings can be applied for the realization of a THz nano-metric generator.

PMID- 23546137
TI  - Toward real-time quantum imaging with a single pixel camera.
AB  - We present a workbench for the study of real-time quantum imaging by measuring
      the frame-by-frame quantum noise reduction of multi-spatial-mode twin beams
      generated by four wave mixing in Rb vapor. Exploiting the multiple spatial modes
      of this squeezed light source, we utilize spatial light modulators to selectively
      pass macropixels of quantum correlated modes from each of the twin beams to a
      high quantum efficiency balanced detector. In low-light-level imaging
      applications, the ability to measure the quantum correlations between individual
      spatial modes and macropixels of spatial modes with a single pixel camera will
      facilitate compressive quantum imaging with sensitivity below the photon shot
      noise limit.

PMID- 23546138
TI  - Femtosecond pulse shaping by modulating the refractive index modulation of volume
      holographic grating.
AB  - Based on the modified Kogelnik's coupled-wave theory, time- and frequency-domain
      diffractions of a femtosecond pulse from transmitted volume holographic gratings
      (VHGs) are theoretically studied. Results show that when the refractive index
      modulation of the VHG changes in a certain range, the number of temporal
      diffracted pulse will evolve from one to two, then to three, and this pulse
      number evolution is periodic. This particular phenomenon can be explained by
      diffraction intensity spectrum and the overmodulation effect of refractive index
      modulation of transmitted VHG. Moreover, we find centers of all temporal
      diffracted pulses translate along the negative time axis, and the translation is
      irrelevant to the refractive index modulations. We will use time delay of volume
      grating to give a reasonable explanation.

PMID- 23546139
TI  - Gain-switched pulses from InGaAs ridge-quantum-well lasers limited by intrinsic
      dynamical gain suppression.
AB  - Gain-switched pulses of InGaAs double-quantum-well lasers fabricated from
      identical epitaxial laser wafers were measured under both current injection and
      optical pumping conditions. The shortest output pulse widths were nearly
      identical (about 40 ps) both for current injection and optical pumping; this
      result attributed the dominant pulse-width limitation factor to the intrinsic
      gain properties of the lasers. We quantitatively compared the experimental
      results with theoretical calculations based on rate equations incorporating gain
      nonlinearities. Close consistency between the experimental data and the
      calculations was obtained only when we assumed a dynamically suppressed gain
      value deviated from the steady-state gain value supported by standard microscopic
      theories.

PMID- 23546140
TI  - Sub-wavelength focusing meta-lens.
AB  - We show that a planar plasmonic metamaterial with spatially variable meta-atom
      parameters can focus transmitted light into sub-wavelength hot-spots located
      beyond the near-field of the metamaterial. By nano-structuring a gold film we
      created an array of meta-lenses generating foci of 160 nm (0.2lambda) in diameter
      when illuminated by a wavelength of 800 nm. We attribute the occurrence of sub
      wavelength hotspots beyond the near field to the phenomenon of superoscillation.

PMID- 23546141
TI  - Influence of output coupling on the performance of a passively Q-switched Nd:YAG
      laser with intracavity optical parametric oscillator.
AB  - A singly-resonant intracavity optical parametric oscillator (OPO), pumped by a
      passively Q-switched Nd:YAG laser, is systematically investigated by means of a
      series of the output mirrors with various reflectivities for the fundamental
      wavelength at 1064 nm. Experimental results reveal that the output mirror with
      partial reflectivity instead of high reflection at 1064 nm not only is
      practicable to avoid the optical coatings damaged, but also enhances the dual
      wavelength output efficiency for the OPO signal and fundamental laser waves. The
      overall optical-to-optical conversion efficiency is enhanced from 6.4% to 8.2%
      for the reflectivity decreasing from 99.8% to 90%.

PMID- 23546143
TI  - High harmonic spectra contributed by HOMO-1 orbital of aligned CO2 molecules.
AB  - We observe the high harmonic generation (HHG) from anti-aligned CO(2) molecules
      when the on-axis peak of HHG from HOMO-2 orbital disappears. The harmonic
      emission at anti-alignment can be attributed to the contribution of HOMO-1
      orbital. Simulations reproduce these observations and reveal the angular
      distributions of tunneling ionization from HOMO and HOMO-1 respectively at
      different intensity. The determination of HOMO-1 orbital contributions in
      harmonic spectra is important for the tomography imaging of aligned molecules and
      analysis of the time evolved harmonic emission.

PMID- 23546142
TI  - Evidence of Tm impact in low-photodarkening Yb-doped fibers.
AB  - In contrast to Yb/Al-doped fibers, the influence of very low Tm(2)O(3)
      concentrations (>= 0.1 mol-ppm) on photodarkening (PD) is clearly detectable in
      Yb/P-doped fibers that are known to show little degradation effects. For
      Tm(2)O(3) additions of more than 50 mol-ppm, the measured PD loss is even similar
      to Yb/Al-doped fibers with comparable rare earth concentrations. Our work reveals
      the risk of color center generation by pumping at wavelengths of 915 nm or 976 nm
      even in Al-free Yb-doped fibers and emphasizes the importance of high purity of
      raw materials for the preparation of Yb laser fibers with expected very low PD.

PMID- 23546144
TI  - Complex liquid crystal alignments accomplished by Talbot self-imaging.
AB  - We introduce Talbot self-imaging into photoalignment technique to record Talbot
      carpet into an LC cell. Through the design of the setup, different images are
      presented on a single sample. By taking a simple 1D grating mask as an example,
      an LC cell with complex alignment structures applicable as Mach-Zehnder
      interferometer arrays is demonstrated. Further mask design permits feasibility of
      various structures which are practicable for many applications. This method may
      facilitate the fabrication of photonic applications such as optical
      communication, computing and sensing, etc.

PMID- 23546145
TI  - Graphene-based tunable hyperbolic metamaterials and enhanced near-field
      absorption.
AB  - We investigate a novel implementation of hyperbolic metamaterial (HM) at far
      infrared frequencies composed of stacked graphene sheets separated by thin
      dielectric layers. Using the surface conductivity model of graphene, we derive
      the homogenization formula for the multilayer structure by treating graphene
      sheets as lumped layers with complex admittances. Homogenization results and
      limits are investigated by comparison with a transfer matrix formulation for the
      HM constituent layers. We show that infrared iso-frequency wavevector dispersion
      characteristics of the proposed HM can be tuned by varying the chemical potential
      of the graphene sheets via electrostatic biasing. Accordingly, reflection and
      transmission properties for a film made of graphene-dielectric multilayer are
      tunable at terahertz frequencies, and we investigate the limits in using the
      homogenized model compared to the more accurate transfer matrix model. We also
      propose to use graphene-based HM as a super absorber for near-fields generated at
      its surface. The power emitted by a dipole near the surface of a graphene-based
      HM is increased dramatically (up to 5 * 10(2) at 2 THz), furthermore we show that
      most of the scattered power is directed into the HM. The validity and limits of
      the homogenized HM model are assessed also for near-fields and show that in
      certain conditions it overestimates the dipole radiated power into the HM.

PMID- 23546146
TI  - Terahertz conductivity of reduced graphene oxide films.
AB  - We performed time-domain terahertz (THz) spectroscopy on reduced graphene oxide
      (rGO) network films coated on quartz substrates from dispersion solutions by
      spraying method. The rGO network films demonstrate high conductivity of about 900
      S/cm in the THz frequency range after a high temperature reduction process. The
      frequency-dependent conductivities and the refractive indexes of the rGO films
      have been obtained and analyzed with respect to the Drude free-electron model,
      which is characterized by large scattering rate. Finally, we demonstrate that the
      THz conductivities can be manipulated by controlling the reduction process, which
      correlates well with the DC conductivity above the percolation limit.

PMID- 23546147
TI  - Route diversity analyses for free-space optical wireless links within turbulent
      scenarios.
AB  - Free-Space Optical (FSO) communications link performance is highly affected when
      propagating through the time-spatially variable turbulent environment. In order
      to improve signal reception, several mitigation techniques have been proposed and
      analytically investigated. This paper presents experimental results for the route
      diversity technique evaluations for a specific case when several diversity links
      intersects a common turbulent area and concurrently each passing regions with
      different turbulence flows.

PMID- 23546148
TI  - Analytical formulation of directly modulated OOFDM signals transmitted over an
      IM/DD dispersive link.
AB  - We provide an analytical study on the propagation effects of a directly modulated
      OOFDM signal through a dispersive fiber and subsequent photo-detection. The
      analysis includes the effects of the laser operation point and the interplay
      between chromatic dispersion and laser chirp. The final expression allows to
      understand the physics behind the transmission of a multi-carrier signal in the
      presence of residual frequency modulation and the description of the induced
      intermodulation distortion gives us a detailed insight into the diferent
      intermodulation products which impair the recovered signal at the receiver-end
      side. Numerical comparisons between transmission simulations results and those
      provided by evaluating the expression obtained are carried out for different
      laser operation points. Results obtained by changing the fiber length, laser
      parameters and using single mode fiber with negative and positive dispersion are
      calculated in order to demonstrate the validity and versatility of the theory
      provided in this paper. Therefore, a novel analytical formulation is presented as
      a versatile tool for the description and study of IM/DD OOFDM systems with
      variable design parameters.

PMID- 23546149
TI  - Effect of irregularities of nanosatellites position and size on collective
      electric and magnetic plasmonic resonances in spherical nanoclusters.
AB  - Spherical nanoclusters (NCs) with a central dielectric core surrounded by several
      satellite plasmonic nanospheres have been recently investigated as aggregates
      supporting electric and magnetic collective resonances. Notably, the collective
      magnetic resonance has been exploited to provide magnetic properties in optics,
      i.e., materials with macroscopic relative permeability different from unity. The
      NCs discussed in this paper can be realized using state-of-the-art nanochemistry
      self-assembly techniques. Accordingly, perfectly regular disposition of the
      nanoplasmonic satellites is not possible and this paper constitutes the first
      comprehensive analysis of the effect of such irregularities onto the electric and
      magnetic collective resonances. In particular we will show that the peak of the
      scattering cross section associated to the magnetic resonance is very sensitive
      to certain irregularities and significantly less to others. It is shown here that
      "artificial magnetic" properties of NCs are preserved for certain degrees of
      irregularities of the nanosatellites positions, however they are strongly
      affected by irregularities in the plasmonic nanosatellites sizes and by the
      presence of "defects" caused by the absence of satellites in the process of self
      assembly around the dielectric core. The "artificial electric" resonance is
      instead less affected by irregularities mainly because of its wider frequency
      bandwidth.

PMID- 23546150
TI  - Experimental investigation of the systematic error on photomechanic methods
      induced by camera self-heating.
AB  - The systematic error for photomechanic methods caused by self-heating induced
      image expansion when using a digital camera was systematically studied, and a new
      physical model to explain the mechanism has been proposed and verified. The
      experimental results showed that the thermal expansion of the camera outer case
      and lens mount, instead of mechanical components within the camera, were the main
      reason for image expansion. The corresponding systematic error for both image
      analysis and fringe analysis based photomechanic methods were analyzed and
      measured, then error compensation techniques were proposed and verified.

PMID- 23546151
TI  - Selection rule for Dirac-like points in two-dimensional dielectric photonic
      crystals.
AB  - We developed a selection rule for Dirac-like points in two-dimensional dielectric
      photonic crystals. The rule is derived from a perturbation theory and states that
      a non-zero, mode-coupling integral between the degenerate Bloch states guarantees
      a Dirac-like point, regardless of the type of the degeneracy. In fact, the
      selection rule can also be determined from the symmetry of the Bloch states even
      without computing the integral. Thus, the existence of Dirac-like points can be
      quickly and conclusively predicted for various photonic crystals independent of
      wave polarization, lattice structure, and composition.

PMID- 23546152
TI  - Adaptive broadband continuum source at 1200-1400 nm based on an all-fiber dual
      wavelength master-oscillator power amplifier and a high-birefringence fiber.
AB  - We experimentally analyze the stimulated Raman scattering characteristics of a
      high-birefringence fiber (HBF), which presents an extraordinary level of spectral
      broadening incurred by the strong nonlinear interaction between the pump and
      Stokes pulses via the polarization-mode dispersion and group-velocity dispersion
      of the fiber. We also investigate the impact of the inter-pulse time-delay on the
      additional spectra broadening when dual-wavelength pump pulses are used.
      Exploiting these unique SRS properties of the HBF, we develop a novel Raman
      continuum source based on an all-fiber dual-wavelength master-oscillator power
      amplifier that can generate a dip-free spectrum in the 1200-1400-nm spectral
      range. We finally obtain a broadband continuum having an average power of ~840 mW
      and a 3-dB bandwidth of ~240 nm centered at 1200-1400 nm, which also represents a
      good spectral flatness and conversion efficiency. This type of source is very
      useful and important for optical coherence tomography applications, for example.

PMID- 23546153
TI  - Resolution enhancement in digital holography by self-extrapolation of holograms.
AB  - It is generally believed that the resolution in digital holography is limited by
      the size of the captured holographic record. Here, we present a method to
      circumvent this limit by self-extrapolating experimental holograms beyond the
      area that is actually captured. This is done by first padding the surroundings of
      the hologram and then conducting an iterative reconstruction procedure. The
      wavefront beyond the experimentally detected area is thus retrieved and the
      hologram reconstruction shows enhanced resolution. To demonstrate the power of
      this concept, we apply it to simulated as well as experimental holograms.

PMID- 23546154
TI  - Reconfigurable photonic radar warning receiver based on cascaded grating.
AB  - A photonic radar warning receiver was conceived and practically demonstrated. The
      system was very flexible in terms of frequency measurement range and resolution.
      This was achieved using a cascaded grating which provided different time delays
      for different wavelengths. The system was thus able to become reconfigured to
      operate at both broadband, low resolution and narrow band, high resolution modes.

PMID- 23546155
TI  - High contrast ballistic imaging using femtosecond optical Kerr gate of tellurite
      glass.
AB  - We investigated the ballistic imaging technique using femtosecond optical Kerr
      gate of a tellurite glass. High contrast images of an object hidden behind turbid
      media were obtained. Compared to the conventional femtosecond optical Kerr gate
      using fused quartz, the optical Kerr gate using tellurite glass has more capacity
      to acquire high quality images of the object hidden behind a high optical density
      turbid medium. The experimental results indicated that the tellurite glass is a
      good candidate as the optical Kerr material for the ballistic imaging technique
      due to its large optical nonlinearity.

PMID- 23546156
TI  - Optimal design of suspended silica on-chip splitter.
AB  - Photonic splitters and couplers are one of the fundamental elements in integrated
      optical circuits. As such, over the past decade significant research efforts have
      been dedicated to the development of low loss, wide bandwidth devices. While
      silica-based devices have clear advantages in terms of bandwidth, silicon and
      silicon nitride devices have lead the field in terms of ease of integration. In
      the present work, we provide design parameters for a novel splitter based on a
      suspended silica device. Unlike previous coupler devices which have smooth
      transition regions, the proposed device has a small defect which enables coupling
      across a large membrane. The designs are based on 3D FDTD models, and incorporate
      wavelength, refractive index and polarization dependence. The model is
      experimentally verified at select wavelengths from the visible through the near
      IR. For comparison, we have also modeled the splitting ratio for several
      materials which are commonly used as waveguiding devices.

PMID- 23546157
TI  - Four-group stabilized zoom lens design of two focal-length-variable elements.
AB  - We present a theoretical method for analyzing the first-order optics of
      stabilized zoom lenses with two focal-length-variable elements. The zoom
      equations are established through the use of the Gaussian brackets method. This
      is done because the optical power of the focal-length-variable elements varies
      during the zooming process. The first and second derivatives and the Hessian
      matrix of the zoom equations with respect to the Gaussian parameters are
      determined using the equations. These parameters could represent the sensitivity
      of the zoom ratio of the system to changes in the corresponding system variables.
      We select the initial values of these system variables, i.e. the magnification of
      the focal-length-variable element and the structure parameters of the fixed lens
      group, to be close to the steepest gradient direction. Here the sensitivity of
      the system focal length is high with respect to variations in the zoom variables.
      This process leads to an increase in the zoom ratio of the zoom system. The
      results show successful four-group stabilized zoom lens designs with 2:1 and 5:1
      zoom ratios, using two deformable mirrors as focal-length-variable elements. This
      system, with the inherent characteristics of a steepest gradient, could
      miniaturize zoom systems.

PMID- 23546158
TI  - New methods of data calibration for high power-aperture lidar.
AB  - For high power-aperture lidar sounding of wide atmospheric dynamic ranges, as in
      middle-upper atmospheric probing, photomultiplier tubes' (PMT) pulse pile-up
      effects and signal-induced noise (SIN) complicates the extraction of information
      from lidar return signal, especially from metal layers' fluorescence signal.
      Pursuit for sophisticated description of metal layers' characteristics at far
      range (80~130km) with one PMT of high quantum efficiency (QE) and good SNR,
      contradicts the requirements for signals of wide linear dynamic range (i.e. from
      approximate 10(2) to 10(8) counts/s). In this article, Substantial improvements
      on experimental simulation of Lidar signals affected by PMT are reported to
      evaluate the PMTs' distortions in our High Power-Aperture Sodium LIDAR system. A
      new method for pile-up calibration is proposed by taking into account PMT and
      High Speed Data Acquisition Card as an Integrated Black-Box, as well as a new
      experimental method for identifying and removing SIN from the raw Lidar signals.
      Contradiction between the limited linear dynamic range of raw signal (55~80km)
      and requirements for wider acceptable linearity has been effectively solved,
      without complicating the current lidar system. Validity of these methods was
      demonstrated by applying calibrated data to retrieve atmospheric parameters (i.e.
      atmospheric density, temperature and sodium absolutely number density), in
      comparison with measurements of TIMED satellite and atmosphere model. Good
      agreements are obtained between results derived from calibrated signal and
      reference measurements where differences of atmosphere density, temperature are
      less than 5% in the stratosphere and less than 10K from 30km to mesosphere,
      respectively. Additionally, approximate 30% changes are shown in sodium
      concentration at its peak value. By means of the proposed methods to revert the
      true signal independent of detectors, authors approach a new balance between
      maintaining the linearity of adequate signal (20-110km) and guaranteeing good SNR
      (i.e. 10(4):1 around 90km) without debasing QE, in one single detecting channel.
      For the first time, PMT in photon-counting mode is independently applied to
      subtract reliable information of atmospheric parameters with wide acceptable
      linearity over an altitude range from stratosphere up to lower thermosphere (20
      110km).

PMID- 23546159
TI  - Toward an ultra-broadband emission source based on the bismuth and erbium co
      doped optical fiber and a single 830nm laser diode pump.
AB  - We demonstrate a broadband optical emission from Bi/Er co-doped fiber and a
      single 830nm laser diode pump. The ultra-broadband mechanism is studied and
      discussed in details based on a combination of experimental measurements,
      including luminescence, differential luminescence and ESA, on fiber samples of
      different Bi and Er concentrations. The Er co-doping in Bi doped fiber is found
      to be effective for broadband emission, by enhancing not only luminescence at C
      and L bands but also that at O and shorter wavelength bands. The luminescence
      intensity between 1100 and 1570nm is over -45dBm/5nm in single mode fiber using a
      few meters of Bi/Er co-doped fiber and offers a modest ~40dB dynamic range and a
      broad bandwidth of ~470nm for an OSA based spectral measurement.

PMID- 23546160
TI  - Fundamental limits to slow-light arrayed-waveguide-grating spectrometers.
AB  - We present an analytical model that describes the limiting spectral performance
      of arrayed-waveguide-grating (AWG) spectrometers that incorporate slow-light
      methods. We show that the loss-limited spectral resolution of a slow-light
      grating-based spectrometer scales as the loss-group-index ratio of the waveguide
      array. We further show that one can achieve a spectral resolution of a few GHz
      using currently available slow-light photonic crystal waveguides while greatly
      shrinking the on-chip footprint of the spectrometer.

PMID- 23546161
TI  - Fabrication of high-quality ZnTe nanowires toward high-performance rigid/flexible
      visible-light photodetectors.
AB  - ZnTe is an important p-type semiconductor with great applications as field-effect
      transistors and photodetectors. In this paper, individual ZnTe nanowires based
      field-effect transistors was fabricated, showing evident p-type conductivity with
      an effect mobility of 11.3 cm(2)/Vs. Single ZnTe nanowire based photodetectors on
      rigid silicon substrate exhibited high sensitivity and excellent stability to
      visible incident light with responstivity and quantum efficiency as high as 1.87
      * 10(5) A/W and 4.36 * 10(7)% respectively and are stable in a wide temperature
      range (25-250  degrees C). The polarization-sensitivity of the ZnTe nanowires was
      studied for the first time. The results revealed a periodic oscillation with the
      continuous variation of polarization angles. Besides, flexible photodetectors
      were also fabricated with the features of excellent flexibility, stability and
      sensitivity to visible incident light. Our work would enable application
      opportunities in using ZnTe nanowires for ultrahigh-performance photodetectors in
      scientific, commercial and industrial applications.

PMID- 23546162
TI  - Tunable plasmon resonances and two-dimensional anisotropy of angular optical
      response of overlapped nanoshells.
AB  - Symmetry breaking of metallic nanoparticles results in many unique optical
      properties. We use the discrete dipole approximation method to study the optical
      properties of overlapped nanoshells which further break the rotational symmetry
      compared with the semishells. The optical properties of the nanoparticles can be
      tuned from the visible to near infrared regime by varying the geometry parameters
      and the hybrid components of nanoparticles. The calculated extinction spectra
      show the two-dimensional anisotropy of the angular optical response of the
      nanoparticles. The plasmon hybridization model provides a way to interpret the
      resonance modes of the nanoparticles. The tunable plasmon resonances, the
      enhanced local fields and the anisotropic optical properties suggest that the
      overlapped nanoshells have potential applications in surface-enhanced
      spectroscopy and "smart" coating in windows or display devices.

PMID- 23546163
TI  - Self-frequency-doubled BaTeMo2O9 Raman laser emitting at 589 nm.
AB  - In this paper, the spontaneous Raman spectra and second harmonic generation (SHG)
      properties at 589 nm of a novel Raman crystal BaTeMo(2)O(9) (BTM) were
      investigated. The BTM crystal was cut along the type-II SHG phase-matching
      direction for the first-order Raman shift at 1178 nm to realize the SRS and SHG
      simultaneously. Pumped by a nanosecond 1064 nm laser source, a self-frequency
      doubled BTM Raman laser operating at 589 nm has been demonstrated for the first
      time. At the pump pulse energy of 48 mJ, the maximum yellow laser output pulse
      energy of 5.6 mJ was obtained with an optical-to-optical conversion efficiency of
      11.7%. Our results show that BTM crystal is one of the promising candidate Raman
      materials to generate yellow laser radiation.

PMID- 23546164
TI  - Polarization diversity DPSK demodulator on the silicon-on-insulator platform with
      simple fabrication.
AB  - We demonstrate a novel polarization diversity differential phase-shift keying
      (DPSK) demodulator on the SOI platform, which is fabricated in a single
      lithography and etching step. The polarization diversity DPSK demodulator is
      based on a novel polarization splitter and rotator, which consists of a tapered
      waveguide followed by a 2 * 2 multimode interferometer. A lowest insertion loss
      of 0.5 dB with low polarization dependent loss of 1.6 dB and low polarization
      dependent extinction ratio smaller than 3 dB are measured for the polarization
      diversity circuit. Clear eye-diagrams and a finite power penalty of only 3 dB
      when the input state of polarization is scrambled are obtained for 40 Gbit/s non
      return-to-zero DPSK (NRZ-DPSK) demodulation.

PMID- 23546165
TI  - Lateral light scattering in fibrous media.
AB  - Lateral light scattering in fibrous media is investigated by computing the
      modulation transfer function (MTF) of 22 paper samples using a Monte Carlo model.
      The simulation tool uses phase functions from infinitely long homogenous
      cylinders and the directional inhomogeneity of paper is achieved by aligning the
      cylinders in the plane. The inverse frequency at half maximum of the MTF is
      compared to both measurements and previous simulations with isotropic and
      strongly forward single scattering phase functions. It is found that the conical
      scattering by cylinders enhances the lateral scattering and therefore predicts a
      larger extent of lateral light scattering than models using rotationally
      invariant single scattering phase functions. However, it does not fully reach the
      levels of lateral scattering observed in measurements. It is argued that the
      hollow lumen of a wood fiber or dependent scattering effects must be considered
      for a complete description of lateral light scattering in paper.

PMID- 23546166
TI  - Nearly degenerate wavelength-multiplexed polarization entanglement by cascaded
      optical nonlinearities in a PPLN ridge waveguide device.
AB  - In this paper we report the generation of wavelength-multiplexed polarization
      entangled photon pairs in the 1.5-MUm communication wavelength band by using
      cascaded optical second nonlinearities (sum-frequency generation and subsequent
      spontaneous parametric down-conversion, c-SFG/SPDC) in a periodically poled
      LiNbO(3) ridge waveguide device. The c-SFG/SPDC method makes it possible to fully
      use the broad spectral bandwidth of SPDC in nearly frequency-degenerate
      conditions, and can provide more than 50 pairs of wavelength channels for the
      entangled photon pairs in the 1.5-MUm wavelength band, using only standard
      optical resources in the telecom field. Visibilities higher than 98% were clearly
      observed in two-photon interference fringes for all the wavelength channels under
      investigation (eight pairs). We further performed a detailed experimental
      investigation of the cross-talk characteristics and the impact of detuning the
      pump wavelengths.

PMID- 23546167
TI  - A label-free supersandwich electrogenerated chemiluminescence method for the
      detection of DNA methylation and assay of the methyltransferase activity.
AB  - A method based on electrogenerated chemiluminescence (ECL) for detection of DNA
      methylation and assay of the methyltransferase activity is developed, and it is
      demonstrated that the label-free ECL method is capable of detecting
      methyltransferase with a detection limit of 3 * 10(-6) U mL(-1), using a
      supersandwich amplification technique.

PMID- 23546168
TI  - Population structure confounds autism genetic classifier.

PMID- 23546170
TI  - Functional SNPs are enriched for schizophrenia association signals.

PMID- 23546169
TI  - Clinical application of brain imaging for the diagnosis of mood disorders: the
      current state of play.
AB  - In response to queries about whether brain imaging technology has reached the
      point where it is useful for making a clinical diagnosis and for helping to guide
      treatment selection, the American Psychiatric Association (APA) has recently
      written a position paper on the Clinical Application of Brain Imaging in
      Psychiatry. The following perspective piece is based on our contribution to this
      APA position paper, which specifically emphasized the application of neuroimaging
      in mood disorders. We present an introductory overview of the challenges faced by
      researchers in developing valid and reliable biomarkers for psychiatric
      disorders, followed by a synopsis of the extant neuroimaging findings in mood
      disorders, and an evidence-based review of the current research on brain imaging
      biomarkers in adult mood disorders. Although there are a number of promising
      results, by the standards proposed below, we argue that there are currently no
      brain imaging biomarkers that are clinically useful for establishing diagnosis or
      predicting treatment outcome in mood disorders.

PMID- 23546171
TI  - Systematic meta-analyses and field synopsis of genetic association studies of
      violence and aggression.
AB  - A large number of candidate gene studies for aggression and violence have been
      conducted. Successful identification of associations between genetic markers and
      aggression would contribute to understanding the neurobiology of antisocial
      behavior and potentially provide useful tools for risk prediction and therapeutic
      targets for high-risk groups of patients and offenders. We systematically
      reviewed the literature and assessed the evidence on genetic association studies
      of aggression and related outcomes in order to provide a field synopsis. We
      searched PubMed and Huge Navigator databases and sought additional data through
      reviewing reference lists and correspondence with investigators. Genetic
      association studies were included if outcome data on aggression or violent
      behavior either as a binary outcome or as a quantitative trait were provided.
      From 1331 potentially relevant investigations, 185 studies constituting 277
      independent associations on 31 genes fulfilled the predetermined selection
      criteria. Data from variants investigated in three or more samples were combined
      in meta-analyses and potential sources of heterogeneity were investigated using
      subgroup analyses. In the primary analyses, which used relaxed inclusion
      criteria, we found no association between any polymorphism analyzed and
      aggression at the 5% level of significance. Subgroup analyses, including by
      severity of outcome, age group, characteristics of the sample and ethnicity, did
      not demonstrate any consistent findings. Current evidence does not support the
      use of such genes to predict dangerousness or as markers for therapeutic
      interventions. 

PMID- 23546172
TI  - A randomized phase II non-comparative study of pemetrexed-carboplatin and
      gemcitabine-vinorelbine in anthracycline- and taxane-pretreated advanced breast
      cancer patients.
AB  - Pemetrexed-carboplatin and gemcitabine-vinorelbine combination therapies were
      efficacious in phase II and phase III studies as first-line breast cancer
      treatment. Thus, Arm A and Arm B combinations were investigated in patients
      pretreated with anthracycline and taxanes. Women with advanced breast cancer,
      with >=1 measurable lesion per RECIST, were stratified by line of treatment (1st,
      2nd), visceral disease (yes/no), ECOG PS (0-1 vs. 2) and randomized 1:1 to Arm A
      (pemetrexed 600 mg/m2, D1 i.v. q21; carboplatin, AUC 5, D1 i.v. q21) or Arm B
      (gemcitabine 1,200 mg/m2 D1, D8 i.v. q21; vinorelbine 30 mg/m2 D1, D8 i.v. q21).
      Treatment continued until progression. The primary endpoint was objective
      response rate (RR). Secondary endpoints were duration of response (DoR), time-to
      response (TTR), time-to-progressive disease (TTPD), time-to-treatment failure
      (TTTF) and safety. A two-stage design was employed independently for each arm. Of
      135 randomized patients, 125 (Arm A, n=64; Arm B, n=61) qualified for tumor
      response analysis. The mean (standard deviation) number of cycles administered
      was 6.3 (4.13) in Arm A and 6.2 (4.39) in Arm B. Efficacy in Arm A and Arm B
      were: RR (95% CI), 26.6 (16.3-39.1) and 29.5 (18.5-42.6); time-to-events
      (months), DoR 7.7 and 7.5; TTPD, 5.1 and 5.6; TTR, 1.8 and 1.8; TTTF, 4.8 and
      5.1; respectively. Most common grade 3/4 adverse events possibly related to study
      drug were neutropenia, thrombocytopenia, anemia and leucopenia in Arm A and
      neutropenia, leucopenia and fatigue in Arm B. In this study, both combinations
      showed moderate activity as predefined RR was not reached and were well
      tolerated.

PMID- 23546173
TI  - Implantable cardioverter-defibrillator shocks: epidemiology, outcomes, and
      therapeutic approaches.
AB  - IMPORTANCE: Implantable cardioverter-defibrillators (ICDs) have revolutionized
      the approach to the prevention of sudden cardiac death and are commonly used in a
      wide range of high-risk patients, including the large population of patients with
      severe left ventricular systolic dysfunction. The benefit of these devices
      derives from their therapies, including both antitachycardia pacing and high
      energy shocks. However, although these therapies may be life saving, devices can
      also deliver inappropriate shocks. OBJECTIVE: To review ICD therapies (shocks and
      antitachycardia pacing), their effects on health outcomes, and current methods to
      reduce these therapies. EVIDENCE REVIEW: We reviewed clinical evidence on ICD
      shocks and reference lists of retrieved articles. We also examined literature
      about the methods of reducing ICD therapy. FINDINGS: Both appropriate and
      inappropriate ICD shocks are common and are associated with an adverse effect on
      health outcomes, quality of life, and mortality. Several methods are available to
      reduce the risk of inappropriate ICD therapies. CONCLUSIONS AND RELEVANCE:
      Implantable cardioverter-defibrillators reduce the risk of sudden cardiac death
      and prolong life in selected populations; however, many patients will receive an
      ICD shock, either appropriate or inappropriate. It is imperative that patients be
      counseled regarding this risk and adverse outcomes associated with shocks.
      Reduction of ICD shock should be individualized to ensure that patients receiving
      these devices experience the maximal benefits of therapy while minimizing the
      adverse consequences.

PMID- 23546174
TI  - Overexpression of AKT decreases the chemosensitivity of gastric cancer cells to
      cisplatin in vitro and in vivo.
AB  - Cisplatin (CDDP) is one of the most efficacious and widely used cytotoxic
      anticancer drugs used for the treatment of numerous types of cancer. However, its
      efficacy is limited as a result of acquired drug resistance. AKT overexpression
      may provide a potential mechanism leading to the resistance of human gastric
      cancer cells; however, the precise mechanism of the development of CDDP drug
      resistance remains uncertain. In the present study, we demonstrate that CDDP
      resistance is associated with AKT overexpression at the cellular and molecular
      level. We also observed that increased expression levels of AKT were sufficient
      to inhibit the resistance of gastric cancer cells to CDDP and that overexpressed
      AKT interacted with reactive oxygen species which were generated by CDDP. These
      results indicate that AKT activity is essential for the regulation of CDDP
      resistance in gastric cancer cells. Our results further demonstrate that AKT
      induces gastric cancer cells to become resistant to CDDP through the Janus kinase
      2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling
      pathway. Taken together, these data support a potential role for AKT
      overexpression and the JAK2/STAT3 pathway in the development of CDDP drug
      resistance in human gastric cancer cells. We hypothesize that AKT may represent a
      future pharmacological target for the inhibition of CDDP resistance in human
      cancer.

PMID- 23546175
TI  - Halogen-bonded liquid crystals of 4-alkoxystilbazoles with molecular iodine: a
      very short halogen bond and unusual mesophase stability.
AB  - Complexes of molecular iodine with alkoxystilbazoles are liquid crystals with
      unusually high mesophase stability, predicated on an intermolecular I...I
      contact. Attempts to prepare analogous complexes with bromine led to an
      unexpected electrophilic substitution product.

PMID- 23546176
TI  - Rational morphology control of beta-NaYF4:Yb,Er/Tm upconversion nanophosphors
      using a ligand, an additive, and lanthanide doping.
AB  - We report the systematic control of the morphology of beta-NaYF4:Yb,Er/Tm
      upconversion nanophosphors (UCNPs) from large spheres (37.9 nm) to rods (length =
      60.1 nm, width = 21.5 nm) and from rods to hexagonal prisms (length = 48.8 nm,
      width = 44.0 nm) or small spheres (14.0 nm) by the use of a surfactant, an
      additive, and lanthanide doping. Increasing the ratio of oleic acid (OA) to 1
      octadecene (ODE) caused a decrease in the size of the UCNPs, and increasing the
      OA/ODE ratio above a critical value caused the particle shape to change from a
      sphere to a rod. The length-to-width aspect ratio (AR) of upconversion nanorods
      (UCNRs) was finely manipulated from 1.28 to 2.80. The rounded tips of the UCNRs
      were flattened by adding Cl(-) ions, and the UCNRs changed to hexagonal prisms
      with a controllable AR depending on the quantity of Cl(-) ions. Additionally, the
      morphology of the beta-NaYF4-based UCNPs was controlled by lanthanide doping. The
      size and AR of the UCNRs decreased with Gd(3+) doping, and the UCNRs ultimately
      transformed into small spheres (14.0 nm) with high monodispersity. Doping with
      Ce(3+) ions also decreased the AR of the UCNRs from 2.80 to 1.27. In addition,
      highly transparent polymer composites for 3D volumetric displays were fabricated
      by blending high-AR beta-NaYF4:Yb,Er/Tm UCNRs with polydimethylsiloxane. These
      composites exhibited bright green and blue upconversion light during excitation
      with 980 nm light.

PMID- 23546177
TI  - Regulations of microtubule sliding by Ca2+ and cAMP and their roles in forming
      flagellar waveforms.
AB  - The function of Ca(2+) and cAMP in extruding doublet microtubules from sea urchin
      sperm axoneme and generating flagellar waves was investigated in order to clarify
      the regulatory mechanism of microtubule sliding and the formation mechanism of
      beating patterns of cilia and flagella. Almost all potentially asymmetric
      spermatozoa that were demembranated with Triton in the absence of Ca(2+) and
      reactivated with MgATP(2-) (Gibbons, B.H. and Gibbons, I.R. (1980). J. Cell
      Biol., 84: 13-27), beat with planar waves closely resembling those of the intact
      spermatozoa, whereas potentially symmetric spermatozoa, in which axonemal
      calmodulin was removed by detergent extraction in the presence of millimolar
      Ca(2+) (Brokaw, C.J. and Nagayama, S.M. (1985). J. Cell Biol., 100: 1875-1883),
      beat with three-dimensional waves if they were reactivated with low MgATP(2-). At
      a high MgATP(2-), almost all demembranated spermatozoa beat with planar waves.
      cAMP enhanced the three-dimensionality of the flagellar waves at a low Ca(2+).
      These changes in the flagellar waves were caused by different regulations of the
      microtubule sliding by calcium, cAMP, and MgATP(2-).

PMID- 23546178
TI  - Ectopic expression of syntaxin3 affects behaviors of B16 melanoma by controlling
      actin dynamics.
AB  - The melanin granules are synthesized in melanocytes in the epidermal basal layer
      and the hair matrix. For the effective passage of melanin granules to the
      adjacent keratinocytes, melanocytes utilize unique cytoplasmic delivery system in
      which cytoskeletal network is prominently involved. Here, we show that the t
      SNARE protein syntaxin3, a member of a family of key mediators of the cytoplasmic
      vesicle fusion and potent modulators of cytoskeletal dynamics, dramatically
      affects melanocyte cell behavior. Although plasmalemmal syntaxin3 has been
      detected also on the melanosomes of normal human melanocytes, we noticed that
      mouse melanoma B16 cells had completely lost endogenous syntaxin3. In response to
      the forcible expression of syntaxin3, B16 cells formed well-developed dendritic
      filopodia and accumulated melanin granules in the cytoplasm. We found that
      exogenous syntaxin3 was not expressed at the plasma membrane, but rather,
      localized with non-fibrous F-actin and melanin-packed melanosomes in the
      cytoplasm, by which the assembly/polymerization of actin was dramatically
      impacted and the melanosome secretion was severely suppressed. The syntaxin3
      triggered phenotypic changes were also induced by a syntaxin3 mutant lacking
      SNARE and transmembrane domains, and they were completely reverted by the
      subsequent knockdown of exogenous syntaxin3. This t-SNARE protein may act as a
      regulator of the actin dynamics, rather than a direct vesicle fusion mediator, to
      determine the fundamental properties of melanocytes.

PMID- 23546181
TI  - Low temperature synthesis of wurtzite zinc sulfide (ZnS) thin films by chemical
      spray pyrolysis.
AB  - Zinc sulfide (ZnS) thin films have been synthesized by spray pyrolysis at 310 
      degrees C using an aqueous solution of zinc chloride (ZnCl2) and thioacetamide
      (TAA). Highly crystalline films were obtained by applying TAA instead of thiourea
      (TU) as the sulfur source. X-ray diffraction (XRD) analyses show that the films
      prepared by TAA contained a wurtzite structure, which is usually a high
      temperature phase of ZnS. The crystallinity and morphology of the ZnS films
      appeared to have a strong dependence on the spray rate as well. The asymmetric
      polar structure of the TAA molecule is proposed to be the intrinsic reason of the
      formation of highly crystalline ZnS at comparatively low temperatures. The violet
      and green emissions from photoluminescence (PL) spectroscopy reflected the sulfur
      and zinc vacancies in the film. Accordingly, the photodetectors fabricated using
      these films exhibit excellent response to green and red photons of 525 nm and 650
      nm respectively, though the band gaps of the materials, estimated from optical
      absorption spectroscopy, are in the range of 3.5-3.6 eV.

PMID- 23546179
TI  - Identification and characterization of a novel genetic mutation with prolonged QT
      syndrome in an unexplained postoperative death.
AB  - INTRODUCTION: The human ether-a-go-go-related gene (hERG) encodes the alpha
      subunit of a cardiac potassium channel. Various mutations of hERG, including
      missense mutations, have been reported to cause long QT syndrome (LQTS) and
      severe arrhythmic disorders such as sudden cardiac death. We identified a novel
      hERG frameshift mutation (hERG(DeltaAT)) in the S5-pore region from a LQTS
      patient who died suddenly and analyzed its genetic profile and the molecular and
      electrophysiological behaviors of the protein product to assess the pathogenicity
      of hERG(DeltaAT). METHODS AND RESULTS: We performed direct sequencing of hERG and
      evaluated its transcript level by using a whole blood sample from the patient. We
      performed immunoblotting, immunocytochemistry, and patch-clamp recordings of HEK
      293 T cells transfected with hERG(DeltaAT), wild-type hERG (hERG(WT)), or both.
      The patient demonstrated an AT deletion (c.1735_1736del) in hERG and a decrease
      in hERG mRNA transcripts. HEK-293 T cells showed lower production and cell
      surface expression of hERG(DeltaAT) compared with hERG(WT) protein. In addition,
      the hERG(?AT) protein failed to form functional channels, while the activation
      kinetics of functional channels, presumably consisting of hERG(WT) subunits, were
      unaffected. CONCLUSION: The DeltaAT mutation may decrease the number of
      functional hERG channels by impairing the posttranscriptional and
      posttranslational processing of the mutant product. This decrease may partly
      explain the cardiac symptoms of the patient who was heterozygous for
      hERG(DeltaAT).

PMID- 23546182
TI  - Management of childhood urticaria: current knowledge and practical
      recommendations.
AB  - Urticaria, defined by the presence of wheals and/or angio-edema, is a common
      condition in children, prompting parents to consult physicians. For its
      successful management, paediatric-specific features must be taken into account,
      regarding the identification of eliciting triggers and pharmacological therapy.
      This review systematically discusses the current best-available evidence on
      spontaneous acute and chronic urticaria as well as physical and other urticaria
      types in children. Potential underlying causes, namely infections, food and drug
      hypersensitivity, autoreactivity and autoimmune or other conditions, and
      eliciting stimuli are considered, with practical recommendations for specific
      diagnostic approaches. Second-generation antihistamines are the mainstay of
      pharmacological treatment aimed at relief of symptoms, which require dose
      adjustment for pae-diatric use. Other therapeutic interventions are also
      discussed. In addition, unmet needs are highlighted, aiming to promote research
      into the paediatric population, ultimately aiming at the effective management of
      childhood urticaria. 

PMID- 23546183
TI  - [Risk and (in)security in the police mission].
AB  - This paper introduces a discussion on the history and use of the concepts of risk
      and security applied to the police officer's mission. The text is developed in an
      essay format that shows how both terms developed under the constitution of modern
      industrial societies. The authors begin with the assumption that the
      organizational structure of the police in various parts of the world retains the
      same logic since they were created during the eighteenth and nineteenth centuries
      and that this format is in crisis: whether it is because the concept of risk and
      current management thereof has now become much broader; or because the concept of
      security has also deepened and broadened, fleeing from the scope of the police
      institution. The crisis of the police apparatus is an international issue and the
      authors point to the case of the French police. Reverting to the thoughts of
      important authors in the sociological area, the authors resume the debate on some
      issues that they consider urgent: reformulation of the breadth of the concepts of
      risk and security to understand the police mission; enhancement of the police
      inside and outside corporations; review of the weight of the hierarchical
      rigidity or inflexibility on careers in a plural and flexible society.

PMID- 23546184
TI  - [Transparency and control].

PMID- 23546185
TI  - [A police force for the 21st century: comments on the article by Minayo and
      Adorno].

PMID- 23546186
TI  - [The authors reply].

PMID- 23546187
TI  - [The identity of civil police officers and successive mirroring studies].
AB  - The scope of this paper was to analyze the perceptions of civil police officers
      regarding their professional identity, the institution they belong to and their
      opinion concerning the image society has of their performance. The data are
      derived from a survey focused on their work and health conditions, using a
      questionnaire, interviews and focus groups including managers, sheriffs and
      officers. The relative frequency and average return for answers about working
      conditions, professional fulfillment and life quality improvement after joining
      the institution were then determined. Qualitative questions were selected about
      the officers' opinion of how society perceives the civil police and what it is to
      be a police officer in the area under study using sense interpretation method
      analysis. The results point to a negative image that the police officers believe
      society has about them, which reaffirms the bad image associated with the
      profession. Rejecting this negative identity, they try to distinguish the
      differences between the civil police and the military police officers. The
      conclusion is that action is required to improve working conditions and develop
      channels of dialogue with the community and promote health campaigns.

PMID- 23546188
TI  - [Professional self-image from the perspective of police officers of the State of
      Rio de Janeiro].
AB  - This paper presents the viewpoint of civil and military police officers of the
      State of Rio de Janeiro on the issue of professional and human self-image. It
      adopts five qualitative indicators as parameter of analysis, namely dignity,
      achievement, recognition, security and promising prospects, drawn from the
      sociological theory of social roles and proposals for human resource management.
      From the methodological standpoint, the study provides a contextual analysis of
      texts written by these agents at the end of a closed questionnaire on work,
      health and life conditions, conducted in a series of studies that began in 2003
      and provided material for two books about these categories. The analysis
      considered the relevance given by the authors themselves when they describe their
      situation, using the five indicators mentioned as parameters. The results of this
      study show that the two categories have serious problems with professional self
      image, especially with regard to wages, housing conditions, access to health
      services and to institutional and psychological support.

PMID- 23546189
TI  - [Investigative police work in relation to youth homicides in Belo Horizonte].
AB  - Over the course of the past 30 years, Brazil has experienced an exponential
      increase in its homicide rates, which is a problem that has been aggravated by
      the slaughter of young nonwhite, poor, males living in the shantytowns and
      communities. Given the complexity and the resurgence of the homicide phenomenon
      in Brazil, this article seeks to discuss some of the main effects that these
      trends have had on investigative police work. For this purpose, a long process of
      ethnographic research in six Specialized Homicide Police Units of Belo Horizonte
      (BH) was conducted between the years 2009 and 2010. During this period,
      researchers accompanied the daily routine of these units and conducted several in
      depth interviews with investigators and civil police chiefs. Among the results,
      the mismatch between the increasing complexity of the homicide phenomenon and the
      legal procedures established for investigating the problem in BH should be
      stressed.

PMID- 23546190
TI  - [Psychic suffering among civil police officers in Rio de Janeiro State].
AB  - The paper discusses the relationship between work and psychic suffering among
      police officers in the State of Rio de Janeiro. A questionnaire was filled out by
      these professionals in three separate studies: Capital Baixada Fluminense and
      Interior. The socio-demographic profile, quality of life, health and working
      conditions were investigated. Psychic suffering was measured by the SRQ-20. A
      logistic regression model was used to identify factors associated with psychic
      suffering. The results showed it to be associated with the following variables:
      level of satisfaction with the ability to react to difficult situations;
      performing the work for which the officers were trained; suffering some
      victimization; unit location; problems in the nervous system; and degree of
      satisfaction with life in general. Those who reported problems in the nervous
      system and victimization showed an OR of 7.25 and 3.08, respectively. The
      professionals who considered themselves dissatisfied or very dissatisfied with
      the ability to react to difficult situations and life in general showed an OR of
      10.85 and 6.69, respectively, compared with those who considered themselves
      satisfied or very satisfied. Professionals from the Baixada showed an increased
      risk of psychic suffering compared to a reduced risk among those from the
      Interior.

PMID- 23546191
TI  - [The perception of risk among police officers from different areas of the State
      of Rio de Janeiro].
AB  - This article seeks to identify the perception of risk among police officers in
      the State of Rio de Janeiro based on their areas of operation: Capital, Interior
      and Baixada Fluminense (BF), by analyzing comparative victimization. It is a
      transversal study using the triangulation method. The quantitative research
      investigated 533 police officers in the Capital, 159 in the Interior and 222 in
      the BF; the qualitative approach included interviews with 17 police chiefs and 15
      focus groups in the three areas. The results indicate that risk perceptions of
      officers, and the strategies used to minimize them are characteristics that unite
      them. Despite its universal nature, risk has differentiated gradations in
      relation to function and territory of operation. In the Capital there is greater
      exposure to the risk of confrontation with criminals, less respect for the police
      from the population, though there is greater operational support from the
      corporation. Contrary to perception, victimization is related to the territory:
      67.8% of police officers were victimized in the Capital last year; 13.7% in the
      Interior; and 9.7% in the BF. The expectation is that the analyses will provide
      input for management of technical support and health assistance for police
      officers, considering the specificities of work in the different areas.

PMID- 23546192
TI  - [Occupational stress among female police officers].
AB  - The scope of this study is occupational stress among female police officers in
      Rio de Janeiro. A qualitative approach was initially used (interviews, focal
      groups and observations) to establish their perceptions regarding gender
      differences in the performance of police work, the relationship between
      occupational stress and health issues and the strategies used to mitigate this
      type of stress. A total of 42 participants including female officers and staff
      and operational and health professionals were involved. The participants link
      stress to their daily work, cite a number of symptoms and show how family
      relationships are affected. Stress originates primarily from work management and
      organizational issues. Gender discrimination and harassment are also perceived as
      stressors. Psychic suffering is greater among officers in commanding roles, and
      operational activities are perceived as more stressful due to the risks involved.
      Physical exercise is seen as the most effective strategy to mitigate the
      consequences of stress. The conclusions drawn are that, there is a need for
      organizational and managerial change from the perspective of gender and
      investment in preventive measures that can reduce the consequences of stress
      within the Rio de Janeiro police force.

PMID- 23546194
TI  - [Police and health: interview with the Director-General of Health of the Military
      Police for the State of Rio de Janeiro].

PMID- 23546193
TI  - [Consumption of licit and illicit substances by police officers in the city of
      Rio de Janeiro].
AB  - The consumption of psychoactive substances by civil and military police of the
      city of Rio de Janeiro was investigated. Data was gathered from two cross
      sectional studies on a questionnaire on work and health conditions given to a
      sample from the two corporations. The results show higher frequencies of regular
      consumption of tobacco (23.3% by civil police and 19.1% by military police),
      daily use of alcohol (12% by civil police and 11% by military police) and
      tranquilizers in the past year (13.3% by civil police and 10.1% by military
      police). The consumption of marijuana among officers was 0.1% by civil police and
      1.1% by military police, and cocaine use among the military police was 1.1%.
      Alcohol consumption proved to be intense and causes problems at work and in the
      social and family relationships of these officers. The need for preventive
      policies for addiction and the possible underestimation of information on illicit
      substances is emphasized.

PMID- 23546195
TI  - The response to gender violence among Brazilian health care professionals.
AB  - The scope of this paper is to identify the experience, attitudes and impressions
      of health care professionals (HCPs) in addressing the needs of women patients
      suffering from intimate partner violence (IPV). In-depth interviews were
      conducted with 14 doctors and 11 nurses in Ribeirao Preto. Results show that
      there is an 'apparent invisibility' of IPV, the convenience of a tacit compact of
      silence about such violence on the part of women and HCPs. We studied the reasons
      given by HCPs for failing to deal with IPV. We also addressed the health service
      facility context, and the diversity of the professioinals' responses to violence,
      with indications of the emergence of a more proactive and positive stance.
      Qualitative data analysis highlights previous survey findings. A positive
      response from HCPs shows that there is perhaps some change from a narrow,
      medically-focused model of health care, to a more broadly defined social model.

PMID- 23546196
TI  - [Repercussions of the Maria da Penha law in tackling gender violence].
AB  - This paper presents the declarations about the Maria da Penha law made by a
      sample of women victims and care workers who handle situations of gender violence
      in the city of Porto Alegre. The data are part of a study that investigated the
      critical path followed by women who decide to denounce violence. The statements
      were selected from 45 semi-structured interviews answered by 21 women and 25
      professionals from the police, legal, social and health services and
      nongovernmental institutions. Data were analyzed using NVivo software and one of
      the categories selected was the Maria da Penha law. Most respondents mentioned
      the positive and innovatory aspects of the law, though they also pointed out its
      limitations. The care workers see the legal device as an important tool for
      tackling violence, aligned with international conventions, bringing innovations
      and broadening women's access to justice. In terms of weaknesses, both women and
      care workers stress the inefficiency in the implementation of protective
      measures, the lack of material resources and manpower, the fragmentation of the
      health care network and the movement of conservative sectors in society to
      delegitimize the law.

PMID- 23546197
TI  - [History of adversity, health and psychopathology among prisoners: comparison
      between men and women].
AB  - Adversity in childhood, risk behaviors and psychopathology are highly prevalent
      phenomena in inmate populations and have a strong impact on health. Knowing the
      differences in these variables between the sexes is most important in order to
      develop appropriate intervention strategies in a prison context. By administering
      the Socio-demographic and Life History Questionnaire and the Brief Symptoms
      Inventory, we sought to characterize adverse childhood experiences and relate
      them to risk behaviors and to psychopathological symptoms, and study the
      differences between the 65 male and 42 female detainees in Portuguese prison
      establishments. Men and women report a complex web of adversity in childhood. In
      a range of ten possible categories, a medium value of 5.05 (DP = 2.63) in total
      adversity for women and 2.63 (DP = 2.18) for men was encountered, with the
      prevalence being significantly higher within the female population (Z = -4.33; p
      = .000). A high prevalence of risk behaviors and psychopathological symptoms was
      found in both groups, the latter being higher among females. We concluded that
      the differences between men and women calls for in depth studies in order to
      provide guidelines for intervention projects in specific populations.

PMID- 23546198
TI  - [Male mortality due to external causes in the State of Minas Gerais, Brazil].
AB  - A descriptive study of a time series seeking to assess mortality due to external
      causes in males in the State of Minas Gerais was conducted in the period from
      1999 to 2008, duly identifying the behavior of this group of causes throughout
      the time series. Data were obtained about the male population resident in the
      State of Minas Gerais recorded in the Unified Health System (SUS). Mortality
      rates per 100,000 inhabitants, divided by age group and specific cause were
      calculated. A simple linear regression model was used to check the trends of male
      deaths during the study period. An increase in male mortality in all years of the
      study period was found, rising from 82.7 deaths per 100,000 in 1999 to 95.7
      deaths per 100,000 in 2008, representing a 15.7% increase in the risk of death
      due to external causes. Young male adults (20-39 years) accounted for the
      majority of deaths due to external causes. In relation to traffic accidents,
      there was an increase in mortality rates, especially between 2000 and 2007. The
      rates of suicide and homicide also rose in the period. In conclusion, it is
      necessary to adopt preventive measures, since men are prone to death due to
      external causes, in order to contribute to the inclusion of specific aspects into
      educational programs geared to reverse this trend.

PMID- 23546199
TI  - [Motorcycle accidents in the municipality of Rio Branco in the State of Acre:
      characterization and trends].
AB  - The scope of this paper is to assess traffic accidents involving motorcycles, the
      victims involved and the increase in the fleet compared with other vehicles in
      Rio Branco, State of Acre. It is an epidemiological, descriptive and transversal
      study of accidents between 2005 and 2008 recorded by the Acre State Highway
      Department. There were 3,582 motorcycle accidents and 3,768 victims in the
      period. The motorcycle fleet increased by 72.8%, with involvement in accidents
      increasing by 42.2%, while accidents involving other vehicles only increased by
      9.2%. As regards victims, there is a predominance of men, with rates of 561.1,
      with the age groups of between 20 and 29 and 30 and 39 being the highest, with
      755.4 and 542.2, respectively. With reference to accident characteristics, the
      highest number of accidents - 32.4% - occurred in the afternoon, followed by the
      morning with 29.2% and the evening with 28.9%. 18.3% occurred on Saturdays and
      15.7% on Sundays. Collisions were the commonest kind of accident, with 3,036
      (84.8%) occurrences. The conclusion drawn is that it is essential to stage
      ongoing preventive programs and ensure greater integration among the institutions
      involved, with planning and campaigns to reverse the current situation.

PMID- 23546200
TI  - [The confrontation of sexuality in the professional practice of future
      physicians: the viewpoint of medical interns].
AB  - The subject of sexuality in academic and service institutions is perceived
      through predominantly biological conceptual perspectives, blurring the subjective
      component that is imbued in social and cultural processes. The meanings that
      medical staff construct around sexuality have implications in their professional
      development and practice. This work presents results from a qualitative study
      into the meaning of sexuality among medical interns from the Universidad Autonoma
      Metropolitana-Xochimilco. In-depth interviews were conducted with students during
      their community service. This group was selected because they had finished their
      studies and were performing an independent and autonomous professional practice.
      The results, which were analyzed based on Grounded Theory, revealed three
      dichotomies: biology vs. social construction, individual vs. professional and
      theoretical learning vs. experiences in the community. The most relevant aspect
      revealed was the antagonism found between a medical intern's biology-centered
      academic knowledge and the challenge posed by their patients' reproductive and
      sexual health needs. The interns recognize that they lack the necessary skills to
      face issues of sexuality in their professional practice.

PMID- 23546201
TI  - [Brazilian Comprehensive Health Care Policies for Adolescents, Young Men and the
      Health of Men: political debates and masculinity].
AB  - This paper analyzes the proposal of the Brazilian Comprehensive Health Care
      Policy for Adolescents and Young People - PNAISAJ, and the Brazilian
      Comprehensive Health Care Policy for Men - PNAISH, as policies that introduce a
      new way to address comprehensive health care for these population groups. From
      official documents, the debates among both policies were analyzed to identify: 1)
      how the relational perspective of gender and masculinity were considered in each
      policy; and 2) other key transversal concepts to the policies studied. While the
      category of life cycle marks the PNAISAJ proposal, the gender issue is paramount
      in the PNAISH proposal. We conclude that political texts express the interests
      and understanding of the field of knowledge of protagonists from each of the
      segments analyzed, constituting cultural policies with the power to establish
      some meanings for attention and care of health in different population groups.

PMID- 23546202
TI  - [Functional capacity of the elderly attended in a Unified Health System (SUS)
      program in Belem in the State of Para].
AB  - The objective of this study was to evaluate factors associated with functional
      capacity among the elderly attended in a public health program in Belem in the
      State of Para. A sectional study was conducted with 259 elderly people attended
      in the Hiperdia/SUS program in the period from March to July 2010. The elderly
      were assessed using the modified physical performance test duly validated in
      Brazil. Pearson's Chi-square Test, in addition to variance analysis and logistic
      regression were used for the analysis. The elderly were 68.3 years on average (SD
      +/- 6.2) and 71% were female. After adjustments for conflicting variables, it was
      seen that there were greater chances of worse performance on the test among
      women, the older and less educated individuals, and those complaining of knee
      pain and prior diagnosis of cataracts and fair/bad self-assessment of health.
      Functional capacity is an important health indicator to identify early risks of
      incapacity and requiring a periodic evaluation, in order to seek care strategies
      for maintaining the independence of the elderly.

PMID- 23546203
TI  - The relationship between shift work and sleep patterns in nurses.
AB  - The scope of this study was to evaluate the sleep/wake cycle in shift work
      nurses, as well as their sleep quality and chronotype. The sleep/wake cycle was
      evaluated by keeping a sleep diary for a total of 60 nurses with a mean age of
      31.76 years. The Horne & Ostberg Questionnaire (1976) for the chronotype and the
      Pittsburgh Sleep Quality Index (PSQI) for sleep quality were applied. The results
      revealed a predominance of indifferent chronotypes (65.0%), followed by
      moderately evening persons (18.3%), decidedly evening persons (8.3%), moderately
      morning persons (6.6%) and decidedly morning persons (1.8%). The sleep quality
      perception was analyzed by the visual analogical scale, showing a mean score of
      5.85 points for nighttime sleep and 4.70 points for daytime sleep, which
      represented a statistically significant difference. The sleep/wake schedule was
      also statistically different when considering weekdays and weekends. The PSQI
      showed a mean of 7.0 points, characterizing poor sleep quality. The results
      showed poor sleep quality in shift work nurses, possibly due to the lack of sport
      and shift work habits.

PMID- 23546204
TI  - [Public health policies for workers: analysis of the implementation of
      institutionalization measures in a Brazilian city].
AB  - The creation of the Brazilian Network of Comprehensive Occupational Health Care
      (Renast) in 2002 led to the appearance and increase of Reference Centers for
      Occupational Health (Cerest) in Brazil. In the North Fluminense Region, Cerest
      was inaugurated in 2006 and resulted from the transformation of the former
      Occupational Health Program of the city of Campos dos Goytacazes. In the broader
      context of the history of Occupational Health Programs in Brazil and the creation
      of Renast, this research analyzes the setting up of this Cerest in Campos in the
      State of Rio de Janeiro. In line with Foucault, it examines the specificity of
      its relations of provenance and emergence, conducting a review of the trajectory
      of the Occupational Health Program in the city in question. Documentary analysis,
      participant observation and interviews with Cerest team members were used as
      research tools. The survey revealed some political and social trouble spots. The
      results show that Cerest has a history of isolation and marginalization in the
      region's political and institutional structure. It acts continuously with a
      predominant logic of care since its inception, but it has faced serious political
      obstacles over the course of time in the implementation of actions to promote
      occupational health.

PMID- 23546205
TI  - [Quality of life of groups of women who suffer from breast cancer].
AB  - This study sought to investigate the quality of life of women who suffer from
      breast cancer and are part of a support group, comparing the data gathered from
      mastectomized women who had breast reconstruction and women who had not had
      surgery. It also compared data of women who had quadrantectomy surgery but did
      not need reconstruction and those who had not had reconstruction surgery. It is a
      quantitative transversal study, and data was collected by application of a
      questionnaire to the respondents and by the SF-36 of the WHO. Fifty women with
      average age of 57.2 years participated in the survey. The groups were compared
      against each other - two by two - considering types of surgery, using the Mann
      Whitney Test at a 5% level of significance. The results showed that women who had
      quadrantectomy surgery and did not need reconstruction are those who had the
      highest average scores in all fields and therefore have the best quality of life.
      They are followed by the group of women who had a mastectomy and reconstruction.
      The mastectomized group of women who had not had reconstruction surgery were seen
      to have a very low level of quality of life. They are followed by the group of
      women who had quadrantectomy surgery and also had not had reconstruction.

PMID- 23546206
TI  - [Nutritional care and weight gain in pregnant adolescents: a quantitative and
      qualitative approach].
AB  - This study sought to evaluate the impact of nutritional assistance (intervention)
      on total gestational weight gain in adolescents and to understand the perceptions
      of adolescents regarding the intervention. It is a quantitative and qualitative
      survey using triangulation methods conducted in a public maternity hospital in
      Rio de Janeiro with 204 adolescents, divided into pre-intervention and
      intervention groups. The hypothesis of homogeneity of proportions was tested by
      bivariate and multivariate analysis using Poisson regression with robust
      variance. The qualitative approach was conducted using semi-structured interviews
      with 12 adolescents, whose data were submitted to content analysis. The results
      indicate that the intervention did not have a positive effect on the adequacy of
      total gestational weight gain. The adolescents perceived the dietary plan as a
      set of rules incompatible with their conditions as pregnant women. The category
      "almost every consultation was the same" emerged as a synthesis of the
      perceptions on the intervention. It was concluded that there is a need to
      reassess the technical and scientific marker tools of nutritional assistance and
      turn it into care focused around making shared decisions.

PMID- 23546208
TI  - [Self-perception of people afflicted with leprosy regarding their oral health and
      the need for treatment].
AB  - Leprosy is an infectious disease that has an impact from a physical, social and
      psychological standpoint. The scope of this study was to assess the self
      perception on oral health and need for treatment in leprosy patients in the city
      of Fortaleza, State of Ceara, Brazil. This is a cross-sectional and descriptive
      study, where 100 leprosy patients were given a semi-structured questionnaire to
      fill out. The results of the bivariate analysis between need for treatment and
      socio-economic characteristics showed that only education revealed a statistical
      association (p=0.000). An association was verified between the classification of
      oral health and self-perception of need for treatment (p=0.05). With respect to
      the self-perception of oral health, 36% of the researched subjects classified
      their oral health as good. The self-perception of leprosy patients regarding
      their oral health and need for treatment, together with a clinical evaluation,
      should serve as a guide for the drafting of public policies that aim to foment
      more effective dental treatment for these patients.

PMID- 23546207
TI  - [Methylphenidate in Brazil: a decade of publications].
AB  - Methylphenidate is frequently associated with Attention Deficit Hyperactivity
      disorder (ADHD), though this psychostimulant has been on the market in
      Switzerland, Germany and the US since the 1950s. After its association with ADHD,
      Ritalin has become the world's most widely used psychostimulant. The scope of
      this article is to present the results of an analysis of publications concerning
      the use of Methylphenidate in Brazil over a decade. It seeks to understand how
      the information is presented or omitted in the different printed materials. For
      the analysis, the most important Brazilian psychiatric journals as well as major
      Brazilian newspapers and magazines for the general public for the 1998-2008
      period were consulted. One important point that resulted from analysis of the
      empirical material was the participation of pharmaceutical laboratories in the
      funding of research groups on ADHD. The findings reveal several controversial
      issues in the publications, such as the combination of drugs and psychotherapy,
      as well as issues of addiction and over-prescription.

PMID- 23546209
TI  - [Problems of adherence to the program of prevention of iron deficiency anemia and
      supplementation with iron salts in the city of Vicosa, Minas Gerais, Brazil].
AB  - The scope of this article is to analyze the understanding of mothers and persons
      responsible for infants taking ferrous sulfate supplement about anemia and its
      consequences, assessed by the level of adherence to supplementation. A
      prospective, qualitative and quantitative population study was conducted with non
      anemic children not taking supplements to receive prophylactic supplementation
      with ferrous sulfate for six months. After six months, there was adherence to
      supplementation. Among the 133 children initially eligible for the study, 97
      returned for the second evaluation. Of these, 4 had anemia during the follow-up
      and began treatment and 3 others were brought in by individuals who were unable
      to provide information on use of the supplement. High adherence was showed by
      56.7% of children and low adherence by 43.3%, while 23.3% had interrupted
      supplementation due to the lack of guidance and support of the health service.
      Mothers and persons responsible of the two groups (high and low adherence)
      manifested little knowledge about anemia, its prevention and health consequences
      for the child. More information regarding iron deficiency anemia, routine follow
      up by professionals and evaluation of the perception of individuals involved with
      iron supplementation is necessary.

PMID- 23546210
TI  - [Health conditions, lifestyles and occupational characteristics of teachers in a
      city in southern Brazil].
AB  - Various health complications have been identified among teachers and there is
      little information available about their lifestyle habits. The scope of this
      study was to investigate health conditions, lifestyles and occupational
      characteristics of municipal teachers in Bage in the south of Brazil. A cross
      sectional study involving 414 teachers was conducted by asking the teachers to
      fill out a standardized questionnaire. Descriptive and bivariate analysis
      techniques were employed. Most teachers were females (96.1%) and the mean age was
      40.1 years (SD 9.4). Average teaching experience was 12.4 years (SD 9.5); 59% of
      the teachers had a degree; they taught many working hours per week (31.7 hours,
      SD 10.5) and 62% were absent from work at least once in the last 12 months. Self
      rated heath was good (38.5%); 62.5% of them were physically active; 32.3% were
      overweight and 14.4% obese. They consumed hardly any fruit and vegetables
      (79.6%), had average stress levels of 14.9 points (SD 6.6) and 20.3% reported
      hypertension. Self-reported health was associated with teaching time,
      absenteeism, physical activity, number of meals per day, stress levels and
      hypertension. The prevalence of teachers who rated their health negatively was
      low, however several lifestyle issues were identified, which can be prejudicial
      to the health of these individuals.

PMID- 23546211
TI  - [Off-label prescriptions in Brazil and in the US: legal aspects and paradoxes].
AB  - The scope of this study is to review the legal aspects of off-label prescription
      in Brazil compared to the US regulatory environment, to verify whether or not it
      derives from the structure of the current administrative regulatory process. It
      involved a bibliographic study in English and Portuguese in public databases of
      legislation, articles, books and dissertations using the key words 'off-label,'
      'health law,' 'health regulation,' with respective translations into English. In
      Brasil and the US, health surveillance institutions have no jurisdiction on
      medical practices and cannot restrict off-label prescriptions beyond educational
      campaigns. Indications of use are a recommendation of minimum safety and efficacy
      for product commercialization, but are not a restrictive factor in practice,
      which does not exonerate physicians from civil liability lawsuits. Public
      measures to restrict off-label prescriptions are more common in the control of
      the incentives and dissemination of information to the medical community. Off
      label prescription is a risk-benefit assessment made by the clinician and the
      pros and cons are described in the literature. Brazilian legislation and its
      stance on the subject still lack greater investigation and subsequent measures.

PMID- 23546212
TI  - [Adherence to medication among patients with Parkinson's disease treated at a
      specialized outpatient unit].
AB  - Parkinson's disease is universal and the second most prevalent neurodegenerative
      disease among the elderly affecting between 0.5 and 1% of the population between
      65 and 69 years of age. Adherence to medication is considered the main
      determinant for the effectiveness of treatment, but only recently has it been
      studied in patients with Parkinson's disease. This cross-sectional and
      descriptive study assessed adherence to medication in 112 patients with
      Parkinson's disease who regularly attended the movement disorder outpatient unit
      at the Hospital das Clinicas of the School of Medicine of Ribeirao Preto,
      University of Sao Paulo, using the Morisky and Green test and an instrument that
      assesses attitudes of medicine intake (IAAFTR). Of the patients interviewed, 53%
      failed to adhere to treatment and 52% did not take the medication at the correct
      time. Patients should receive guidance about the importance of taking their
      medication at the correct time, understanding the benefits that adherence to
      medication can provide. They should also be aware that doses not taken, taken in
      excess or not taken at the prescribed times can reduce their response to
      treatment, having a negative effect on the clinical outcome and quality of life,
      thereby generating higher costs to public health in the country.

PMID- 23546213
TI  - [Women with disabilities and their double vulnerability: contributions for
      setting up comprehensive health care practices].
AB  - Women with disabilities have few measures geared to their needs in the primary
      health care services. Despite the attention given to the female population in
      these facilities, they still fail to address specificities of women with
      disabilities, such as issues related to their sexual and reproductive rights and
      their double vulnerability, both as women and as disabled individuals. This
      research is part of a qualitative study to identify the individual, social and
      programmed double vulnerability of fifteen women with different types and degrees
      of disabilities, who are frequenters of three primary health care facilities in
      Sao Paulo city. The women's narratives highlighted experiences of rejection or
      overprotection in their family relationships, difficulties in obtaining equipment
      for their autonomy, poor education and lack of professional qualification, lower
      social participation, obstacles in their sex lives and motherhood. They face
      physical and communication barriers and poor care from primary health care
      services. All of the dimensions of vulnerability are present and addressing them
      makes it possible to build comprehensive health care practices that ensure the
      human rights of groups that historically experience violations, namely women and
      disabled persons.

PMID- 23546214
TI  - [The impact of risk factors of non-communicable chronic diseases on quality of
      life].
AB  - Quality of life has become an important yardstick of the impact on health. Its
      evaluation related to diseases and associated risk factors has increased in the
      population in general. This article seeks to assess the quality of life and the
      presence of the association with risk factors for non-communicable chronic
      diseases in the urban population of the city of Montes Claros in the State of
      Minas Gerais. It is a population-based cross-sectional study. The sample was
      calculated considering the prevalence of risk factors of overweight of 30% and
      corrected for a variation of 30%. Cluster sampling was conducted on urban census
      sectors. Seventeen census sectors were selected and 648 residents aged e" 18
      years were interviewed. The risk factors for non-communicable chronic diseases as
      well as the quality of life were verified using the SF-36 questionnaire. Some
      risk factors were associated with the lowest scores on the SF-36 questionnaire.
      The presence of some risk factors for chronic diseases has an impact on quality
      of life.

PMID- 23546215
TI  - [Guidelines for an Expired Medication Collection Program in Brazil].
AB  - The scope of this paper is to outline and discuss fundamental guidelines for an
      expired medication collection program for Brazil and to provide evidence
      supporting campaigns to raise the population's awareness for the program's
      success. It is a document-based descriptive review that analyzes official,
      technical and regulatory documents from Portugal, Canada and Colombia, where
      there are expired medication collection programs in different stages of
      implementation. Some of them are already fully implemented, while others are in
      the preliminary stages, but all of them are achieving good results. The countries
      listed above were chosen in order to represent Europe, North America and Latin
      America. Six common guidelines were outlined: co-responsibility in the drug's
      manufacturing and distribution chain; a strategy of minimization of waste;
      setting up pilot programs; investigation and classification of waste generated;
      inter-sectorial communication between different government bodies; and campaigns
      to raise the community's awareness. These guidelines represent the ground rules
      for an Expired Medication Collection Program in Brazil.

PMID- 23546218
TI  - Simple heteroatom engineering for tuning the triplet energy of organometallic
      host materials for red, green and blue phosphorescent organic light-emitting
      diodes.
AB  - Triplet energy tuning from 2.48 eV to 2.94 eV by just a simple change of
      heteroatom in the ligand structure of Be complexes was studied using azole based
      triplet host materials. Three Be organometallic host materials with azole type
      ligands were synthesized and could be used as the host materials from red to deep
      blue phosphorescent organic light-emitting diodes. High quantum efficiency was
      obtained in red, green, blue and deep blue devices using the Be complexes. In
      particular, a high quantum efficiency of 26.1% was achieved in blue
      phosphorescent organic light-emitting diodes.

PMID- 23546219
TI  - Functional mesoporous materials for energy applications: solar cells, fuel cells,
      and batteries.
AB  - This feature article presents recent progress made in the synthesis of functional
      ordered mesoporous materials and their application as high performance electrodes
      in dye-sensitized solar cells (DSCs) and quantum dot-sensitized solar cells
      (QDSCs), fuel cells, and Li-ion batteries. Ordered mesoporous materials have been
      mainly synthesized using two representative synthetic methods: the soft template
      and hard template methods. To overcome the limitations of these two methods, a
      new method called CASH was suggested. The CASH method combines the advantages of
      the soft and hard template methods by employing a diblock copolymer, PI-b-PEO,
      which contains a hydrophilic block and an sp(2)-hybridized-carbon-containing
      hydrophobic block as a structure-directing agent. After discussing general
      techniques used in the synthesis of mesoporous materials, this article presents
      recent applications of mesoporous materials as electrodes in DSCs and QDSCs, fuel
      cells, and Li-ion batteries. The role of material properties and mesostructures
      in device performance is discussed in each case. The developed soft and hard
      template methods, along with the CASH method, allow control of the pore size,
      wall composition, and pore structure, providing insight into material design and
      optimization for better electrode performances in these types of energy
      conversion devices. This paper concludes with an outlook on future research
      directions to enable breakthroughs and overcome current limitations in this
      field.

PMID- 23546220
TI  - Application of fluorescence and PARAFAC to assess vertical distribution of
      subsurface hydrocarbons and dispersant during the Deepwater Horizon oil spill.
AB  - We evaluated the use of excitation and emission matrix (EEM) fluorescence and
      parallel factorial analysis (PARAFAC) modeling techniques for monitoring crude
      oil components in the water column. Four of the seven derived PARAFAC loadings
      were associated with the Macondo crude oil components. The other three components
      were associated with the dispersant, an unresolved component and colored
      dissolved organic matter (CDOM). The fluorescence of the associated benzene and
      naphthalene-like components of crude oil exhibited a maximum at ~1200 m. The
      maximum fluorescence of the component associated with the dispersant (i.e.,
      Corexit EC9500A) was observed at the same depth. The plume observed at this depth
      was attributed to the dispersed crude oil from the Deepwater Horizon oil spill.
      Results demonstrate the application of EEM and PARAFAC to simultaneously monitor
      selected PAH, dispersant-containing and humic-like fluorescence components in the
      oil spill region in the Gulf of Mexico.

PMID- 23546221
TI  - Analysis of Latvian familial melanoma patients shows novel variants in the
      noncoding regions of CDKN2A and that the CDK4 mutation R24H is a founder
      mutation.
AB  - Hereditary cutaneous melanoma is associated with mutations in the high-risk
      CDKN2A gene in about 40% of melanoma-prone families. Mutations in the CDK4 gene
      are the cause in only a few pedigrees. In this study, we analyzed 20 Latvian
      familial melanoma probands and carried out a comprehensive analysis of CDKN2A
      including sequencing of its promoter/intronic regions and deletion screening. We
      also analyzed the critical second exon of the CDK4 gene. One novel intronic
      variant (IVS2+82C>T) of the CDKN2A gene and a small deletion (c.-20677_
      20682delGTACGC) in its promoter region were found. Genotyping of the novel
      variants in larger melanoma and control groups indicated that the deletion
      increases the risk of melanoma (odds ratio=6.353, 95% confidence interval: 1.34
      30.22, P=0.0168). The CDK4 gene analysis showed a Latvian melanoma family with
      the mutation R24H carried on the same haplotype as in two previously described
      Latvian CDK4-positive families. Our study suggests that the main risk gene in
      Latvian families with a strong family history of melanoma is CDK4 and that most
      of the other cases analyzed could be sporadic or associated with low-penetrance
      risk genes.

PMID- 23546222
TI  - Highlights of the 2012 Congress of the Society for Melanoma Research, 8-11
      November 2012, Hollywood, CA.
AB  - The 2012 Congress of the Society for Melanoma Research was attended by
      researchers with widespread expertise in basic, translational, and clinical
      research. Exciting research has led to the discovery of therapies to target
      mutations found in melanoma; however, it is clear that much still needs to be
      learned about how to use these therapies and the role of the microenvironment in
      therapy resistance and melanoma progression. This summary highlights recent
      discoveries in genetics and epigenetics, biology, immunotherapy, and targeted
      therapies for melanoma discussed at this year's meeting.

PMID- 23546224
TI  - Mesalamine: a rare constituent of urinary tract concretions.

PMID- 23546223
TI  - Macrolide antibiotics block autophagy flux and sensitize to bortezomib via
      endoplasmic reticulum stress-mediated CHOP induction in myeloma cells.
AB  - The specific 26S proteasome inhibitor bortezomib (BZ) potently induces autophagy,
      endoplasmic reticulum (ER) stress and apoptosis in multiple myeloma (MM) cell
      lines (U266, IM-9 and RPMI8226). The macrolide antibiotics including concanamycin
      A, erythromycin (EM), clarithromycin (CAM) and azithromycin (AZM) all blocked
      autophagy flux, as assessed by intracellular accumulation of LC3B-II and p62.
      Combined treatment of BZ and CAM or AZM enhanced cytotoxicity in MM cell lines,
      although treatment with either CAM or AZM alone exhibited almost no cytotoxicity.
      This combination also substantially enhanced aggresome formation, intracellular
      ubiquitinated proteins and induced the proapoptotic transcription factor CHOP
      (CADD153). Expression levels of the proapoptotic genes transcriptionally
      regulated by CHOP (BIM, BAX, DR5 and TRB3) were all enhanced by combined
      treatment with BZ plus CAM, compared with treatment with each reagent alone. Like
      the MM cell lines, the CHOP+/+ murine embryonic fibroblast (MEF) cell line
      exhibited enhanced cytotoxicity and upregulation of CHOP and its transcriptional
      targets with a combination of BZ and one of the macrolides. In contrast, CHOP-/-
      MEF cells exhibited resistance against BZ and almost completely canceled enhanced
      cytotoxicity with a combination of BZ and a macrolide. These data suggest that ER
      stress-mediated CHOP induction is involved in pronounced cytotoxicity.
      Simultaneously targeting two major intracellular protein degradation systems such
      as the ubiquitin-proteasome system by BZ and the autophagy-lysosome system by a
      macrolide antibiotic enhances ER stress-mediated apoptosis in MM cells. This
      result suggests the therapeutic possibility of using a macrolide antibiotic with
      a proteasome inhibitor for MM therapy.

PMID- 23546225
TI  - Quantum dot imaging for HSP70 and HSF-1 kinetics in SCC-25 cells with or without
      leucine deprivation following heat shock.
AB  - The aim of this study was to develop a quantum dot-based approach for heat shock
      protein 70 (HSP70) and heat shock factor 1 (HSF-1) kinetics following heat shock,
      and to discover approaches to thermotherapy based on disrupting the effect of
      activation of HSF-1 and the accumulation of HSP70 by leucine deprivation. SCC-25
      cells cultured with limiting leucine or normal leucine were stressed at 42C for
      30 min, and were cultured for 2, 4, 6, 8 and 10 h, respectively. The expression
      of HSP70 and HSF-1 was observed using confocal laser microscopy and semi
      quantitative analysis was performed by Image-Pro Plus. At 6 h after heating, HSF
      1 in cells cultured with normal leucine was activated and translocated from the
      cytosol to the nucleus, and the synthesis of HSP70 reached the maximum value and
      had a tendency to gather in the nucleus. However, in cells cultured with limiting
      leucine, HSF-1 activity decreased and accumulation of HSP70 was not found.
      Leucine deprivation results in the inactivation of HSF-1 leading to slight
      accumulation of HSP70 and no tendency to gather in the nucleus. Thus, HSF-1 may
      serve as a novel therapeutic target in the treatment of oral cancer.

PMID- 23546226
TI  - Spontaneously walking discrete cavity solitons.
AB  - We study the dynamics of oscillating discrete solitons in an array of coupled
      Kerr-nonlinear cavities. They emanate from stationary discrete cavity solitons
      due to Hopf instability and are very robust. We show that these oscillating
      solitons can spontaneously lose their spatial symmetry and start rocking around
      the equilibrium position. Moreover they can suddenly jump to adjacent resonators
      starting a chaotic motion along the array, resembling the Brownian motion of
      particles. We also identify the parameter domain where they move with constant
      velocity across the array.

PMID- 23546227
TI  - Bistable liquid crystal devices with nanoparticle-coated polyimide alignment
      films.
AB  - Bistable hybrid-aligned nematic (HAN) liquid crystal devices (LCDs) with silica
      nanoparticle-coated polyimide alignment films were investigated. It was observed
      that the existence of the internal electric field produced from the
      triboelectrically charged silica nanoparticles layer and impurity ions in the LC
      reduced the total free energy of the HAN-LCD and stabilized the cell in the
      homeotropic state. The stable homeotropic state can be switched back to the HAN
      state by changing the ion distribution through a voltage pulse with proper
      polarity. The capability of controlling bistability through modification of ion
      density in the LC layer may have some applications, such as displaying a one-time
      password requiring a specific stable time.

PMID- 23546228
TI  - Compact optical switch based on 2D photonic crystal and magneto-optical cavity.
AB  - A compact optical switch based on a 2D photonic crystal (PhC) and a magneto
      optical cavity is suggested and analyzed. The cavity is coupled to two parallel
      and misaligned PC waveguides and operates with dipole mode. When the cavity is
      nonmagnetized, the dipole mode excited by a signal in the input waveguide has a
      node in the output waveguide. Therefore, the input signal is reflected from the
      cavity. This corresponds to the state off of the switch. Normal to the plane of
      the PhC magnetization by a dc magnetic field produces a rotation of the dipole
      pattern in the cavity providing equal amplitudes of the electromagnetic fields in
      the input and the output waveguides. This corresponds to the state on with high
      transmission of the input signal. Numerical calculations show that at the 1.55
      MUm wavelength the device has the insertion loss -0.42 dB in the on state, the
      isolation -19 dB in the off state and the switch off and on ratio P(on)/P(off)
      about 72. The frequency band at the level of -15 dB of the resonance curve in off
      state is about 160 GHz.

PMID- 23546229
TI  - Target-in-the-loop coherent beam combination of 100 W level fiber laser array
      based on an extended target with a scattering surface.
AB  - Target-in-the-loop coherent beam combination (TIL CBC) of a 100 W level fiber
      laser array has been demonstrated. In the experiment, the beams from nine 10 W
      level fiber amplifiers achieve a scattering surface target after transmitting 10
      m in free space. When the phase control system goes into close loop, atmosphere
      turbulence could be effectively compensated and a stable fringe pattern could be
      obtained on the scattering surface with 85% fringe contrast. To our best
      knowledge, this is the TIL CBC with the highest output power and the largest
      number of laser beams. Additionally, the effect of atmosphere turbulence on the
      backward paths on TIL CBC has been studied experimentally.

PMID- 23546230
TI  - 330 mJ single-frequency Ho:YLF slab amplifier.
AB  - We report on a double-pass Ho:YLF slab amplifier which delivered 350 ns long
      single-frequency pulses of up to 330 mJ at 2064 nm, with a maximum M2 of 1.5 at
      50 Hz. It was end pumped with a diode-pumped Tm:YLF slab laser and seeded with up
      to 50 mJ of single-frequency pulses.

PMID- 23546231
TI  - Coherent polarization locking: an approach to mitigating optical damage in a
      pulsed Ho:YAG laser.
AB  - Intracavity optical damage is mitigated in a pulsed Ho:YAG laser cavity using the
      coherent polarization locking (CPL) technique. By splitting the available pump
      power into two individual Ho:YAG laser rods, we passively coherently locked two
      orthogonal polarization lasers with 9.13 mJ output pulse energies and 14 ns
      pulsewidths, and operating at 800 Hz repetition rate. A conventional Ho:YAG laser
      cavity with the same pump and cavity configuration results in severe optical
      damage when operating at <2 kHz repetition rate, thus limiting the output pulse
      energies to <5 mJ. We also demonstrated, to the best of our knowledge, the first
      pulsed operation within the entire CPL Ho:YAG laser cavity by Q-switching in one
      of the polarization arms, producing nanosecond pulses with no sign of pulse
      instability.

PMID- 23546232
TI  - Two-dimensional subwavelength gratings with different frontside/backside
      reflectance.
AB  - A concept of two-dimensional periodic subwavelength gratings exhibiting different
      reflectance on the front and back sides is presented. This structure incorporates
      an arrangement of a metalized hole array and a nanodot array on top. We exemplify
      the optical properties for an aluminum grating with 243 nm period, and we
      demonstrate its color filtering properties for unpolarized light in reflectance
      as well as in transmittance yielding different colors for frontside and backside
      illumination. These findings have been confirmed by a numerical study. The
      gratings may be replicated by a simple nanoimprint process on plastic foils
      predestined for industrial mass production.

PMID- 23546233
TI  - Air-clad silicon pedestal structures for broadband mid-infrared microphotonics.
AB  - Toward mid-infrared (mid-IR) silicon microphotonic circuits, we demonstrate
      broadband on-chip silicon structures, such as: (i) straight and bent waveguides
      and (ii) beam splitters, utilizing an air-clad pedestal configuration which
      eliminates the need for typical mid-IR-lossy oxide cladding. We illustrate a
      sophisticated fabrication process that can create high-quality pedestal
      structures in crystalline silicon, while preserving its mid-IR transparency. A
      fundamental waveguide mode is observed between lambda=2.5 MUm and lambda=3.7 MUm,
      and an optical loss of 2.7 dB/cm is obtained at lambda=3.7 MUm. Our pedestal
      silicon structures show 50:50 mid-IR power splitting enabling the further
      development of mid-IR silicon microphotonics.

PMID- 23546234
TI  - Mechanism of elliptically polarized terahertz generation in two-color laser
      filamentation.
AB  - We investigate the mechanism of elliptically polarized terahertz (THz) pulse
      generation in femtosecond two-color laser-produced plasma. In the case of in-line
      laser focusing, we observe the THz polarization evolves from linear to elliptical
      with increasing plasma length. This ellipticity arises from two combined effects-
      successive polarization rotation of local THz plasma sources, caused by laser
      phase and polarization modulations, and the velocity mismatch between laser and
      THz, which produces an elliptical THz pulse from a series of time-delayed,
      polarization-rotating local THz fields.

PMID- 23546235
TI  - Guided-wave electro-optic characterization of BaTiO3 thin films using the prism
      coupling technique.
AB  - Ferroelectric BaTiO3 (BTO) thin films are grown by RF sputtering onto an indium
      tin oxide bottom electrode on a MgO single-crystal substrate. We have studied
      here the optical properties by the prism coupling technique. We report the
      ordinary and extraordinary refractive indices of the films, the film thickness,
      and the optical losses that are obtained on the planar waveguides: n0=2.224+/
      0.001 and n(e)=2.219+/-0.001 at 1539 nm. Furthermore, in order to demonstrate the
      active property of the BTO films, we have investigated the electro-optic (EO)
      properties by using the change of the resonant coupling angle (variation of
      fundamental TE0 guided mode) when the transverse electric field is applied. The
      latter is induced by the refractive index variation (Deltan) caused by the EO
      effect when a static electric field is applied transversely to the film. The EO
      coefficient obtain is about 18 pm/V for TE mode and 23 pm/V for TM modes at 1539
      nm. This value illustrates the suitability of the BTO material thin film with a
      polycrystalline structure for applications such as modulations, switching, and
      interconnections.

PMID- 23546236
TI  - Electron-beam-activated light-emitting polymer nanofibers.
AB  - We demonstrate a simple approach to high-stability light-emitting polymer
      nanofibers. We show that nonluminescent polyacrylamide (PAM) nanofibers, when
      being irradiated by electron beams, can be locally activated into light-emitting
      nanofibers with high resistance to photobleaching, precise emission patterns,
      spectrally tunable emission, high repeatability, and great mechanical
      flexibility. Compared to unirradiated nanofibers, the electron-beam-activated PAM
      nanofibers show an obvious increase in refractive index of about 0.1. Due to its
      high versatility, the electron-beam-activated nanofiber demonstrated here
      represents a promising nanometer-scale integratable light source for functional
      nanophotonic circuits or devices.

PMID- 23546237
TI  - Double pass, common path method for arbitrary polarization control using a
      ferroelectric liquid crystal spatial light modulator.
AB  - We present a method for arbitrary control of the polarization of a light beam.
      Our method uses two holograms on a binary ferroelectric liquid crystal spatial
      light modulator (FLCSLM), and so has the potential to allow polarization state
      switching at kilohertz rates. Unlike previous methods that achieve polarization
      control using FLCSLMs, our method is common path and requires only the simplest
      optical components. For this reason, the method is very easy to setup, align, and
      maintain. In addition, it has the ability to modulate unpolarized input light. We
      demonstrate the formation of radially, azimuthally, and circularly polarized
      beams by imaging their focal spots formed at low numerical aperture.

PMID- 23546238
TI  - Low-threshold lasing in active opal photonic crystals.
AB  - We theoretically study a low-threshold band-edge lasing in three-dimensional
      photonic crystals (PhCs) with a face-centered cubic lattice structure, using a
      complex-valued permittivity approach combined with the Korringa-Kohn-Rostoker
      method. We show that the lasing threshold at the low-frequency band edge is
      smaller than that at the high-frequency band edge for the first-order stop band
      of the PhC. We also analyze the impact of the number of the PhC's layers on the
      frequency of band-edge lasing and the lasing threshold near the first-order stop
      band in the GammaL direction, and demonstrate a broad tunability of the lasing
      frequency with change in the emission collection angle. The obtained results are
      beneficial for the performance enhancement of tunable, PhC-based chip lasers.

PMID- 23546239
TI  - Broadband amplification and highly efficient lasing in erbium-doped tellurite
      microstructured fibers.
AB  - We report broadband amplification and highly efficient lasing in erbium-doped
      tellurite microstructured fibers. A broad positive net gain bandwidth of 113 nm
      (1524-1637 nm) is obtained in a 17 cm long erbium-doped tellurite microstructured
      fiber upon a pump power of 94 mW at 1480 nm. An all-fiber lasing at 1561 nm with
      maximum unsaturated power of 140 mW and slope efficiency of 53.7% is achieved
      from the fiber by employing a linear cavity. In addition, the influence of the
      fiber length on amplification and lasing is investigated and laser oscillation at
      1535 nm is realized in a 4.3 cm long fiber.

PMID- 23546240
TI  - Enhancement of Faraday and Kerr rotations in three-layer heterostructure with
      extraordinary optical transmission effect.
AB  - We theoretically investigate and optimize a multilayer planar structure with
      enhanced magneto-optical (MO) activity. The extraordinary optical transmission
      observed in a periodically perforated metal plate with subwavelength holes is
      used to produce a higher MO activity. We consider a three-layer structure that
      consists of a dielectric layer placed between the perforated metal and the MO
      layers. In this structure, we obtained the enhancement of Faraday rotation by
      three times and the Kerr effect by an order as compared to the published results.

PMID- 23546241
TI  - Relative phase noise induced impairment in M-ary phase-shift-keying coherent
      optical communication system using distributed fiber Raman amplifier.
AB  - We show for the first time, to the best of our knowledge, that, in a coherent
      communication system that employs a phase-shift-keying signal and Raman
      amplification, besides the pump relative intensity noise (RIN) transfer to the
      amplitude, the signal's phase will also be affected by pump RIN through the pump
      signal cross-phase modulation. Although the average pump power induced linear
      phase change can be compensated for by the phase-correction algorithm, a relative
      phase noise (RPN) parameter has been found to characterize pump RIN induced
      stochastic phase noise. This extra phase noise brings non-negligible system
      impairments in terms of the Q-factor penalty. The calculation shows that
      copumping leads to much more stringent requirements to pump RIN, and relatively
      larger fiber dispersion helps to suppress the RPN induced impairment. A higher
      order phase-shift keying (PSK) signal is less tolerant to noise than a lower
      order PSK.

PMID- 23546242
TI  - Real-time polarimetric optical sensor using macroporous alumina membranes.
AB  - We report on the demonstration of real-time refractive index sensing within 60
      MUm thick free-standing macroporous alumina membranes with pore diameters of 200
      nm. The free-standing macroporous alumina membranes allow the analytes to flow
      through the pores for targeted delivery, resulting in fast sensing responses. The
      polarimetric measurement platform exploits the optical anisotropy of the
      membranes in monitoring the refractive index variations of the analytes that fill
      the pores, providing highly sensitive and real-time measurements. The
      experimental characterization of the membranes' birefringence at wavelengths of
      808, 980, and 1500 nm showed a decrease in birefringence for shorter wavelengths
      caused by the depolarization process that takes place when polarized light passes
      through a porous medium. Volumetric sensing experiments performed at the same
      wavelengths demonstrated detection limits of 8.1*10(-6), 5.2*10(-6), and 6*10(-6)
      refractive index units at wavelengths of 808, 980, and 1500 nm, respectively.

PMID- 23546243
TI  - Improved fabrication process of low-loss and efficient polarization converters in
      InP-based photonic integrated circuits.
AB  - We show an improved fabrication process of trapezoidal polarization converters
      for InP-based photonic integrated circuits. The new process has reduced
      complexity, and the fabricated converters have loss two times lower than reported
      previously. The measurements of the converters show an efficiency of polarization
      conversion of 97.9% at a wavelength of 1.535 MUm and loss below 0.5 dB.

PMID- 23546244
TI  - Nonlinear surface lattice coupler.
AB  - We study two-component surface solitons in a pair of linearly coupled truncated
      waveguiding arrays with the Kerr nonlinearity. Symmetric solitons have a very
      small stability area, while those that are antisymmetric and asymmetric are
      stable in vast regions. Below a critical value of the coupling constant, branches
      of the symmetric and asymmetric modes separate, and accordingly, asymmetric
      solitons cease to bifurcate from the symmetric ones, providing the first example
      of asymmetric modes in nonlinear couplers that do not originate from symmetric
      counterparts.

PMID- 23546246
TI  - Pulse duration and wavelength stability measurements of a midinfrared free
      electron laser.
AB  - We report the pulse duration and wavelength stability measurements of a
      midinfrared free-electron laser (FEL) where the wavelength fluctuation may not be
      negligible. The technique we employ is a fringe-resolved autocorrelation (FRAC)
      method that has good sensitivity on not only the pulse duration and the chirp but
      also the wavelength stability. By the simple manipulation of experimental FRAC
      signals, we can obtain the pulse duration even if the amounts of the chirp and
      the wavelength stability are not known in advance, which is further used to
      estimate the wavelength stability. Through this procedure we find that the pulse
      duration of the Kyoto University FEL at 12 MUm is about 0.58 ps without any
      notable chirp, and the wavelength stability is about 1.3%. We also carry out
      separate experiments for intensity autocorrelation and sum-frequency mixing. The
      difference we find for pulse duration and wavelength stability by the different
      measurements is attributed to the different operation conditions of FEL.

PMID- 23546247
TI  - Simultaneous measurement of temperature and force with high sensitivities based
      on filling different index liquids into photonic crystal fiber.
AB  - A double-filled photonic crystal fiber (PCF) was fabricated by filling liquids of
      different indexes into two air holes in the cladding. The core mode coupled to
      the local cladding modes LP(01) and LP(11) in the 1310 and 1550 nm wavebands,
      respectively. Due to the unique characteristics of the mode coupling, the
      resonant peaks in different resonance areas shifted to the opposite directions
      with the variations of the temperature or the force. The double-filled PCFs
      achieved in this work showed useful applications in the simultaneous measurement
      of both the temperature and the force.

PMID- 23546248
TI  - Limitations of the paraxial Debye approximation.
AB  - In the paraxial form of the Debye integral for focusing, higher order defocus
      terms are ignored, which can result in errors in dealing with aberrations, even
      for low numerical aperture. These errors can be avoided by using a different
      integration variable. The aberrations of a glass slab, such as a coverslip, are
      expanded in terms of the new variable, and expressed in terms of Zernike
      polynomials to assist with aberration balancing. Tube length error is also
      discussed.

PMID- 23546249
TI  - Thresholdless crescent waves in an elliptical ring.
AB  - By introducing symmetry-breaking in geometry, we reveal the existence of
      thresholdless crescent waves, i.e., nonlinear diffractionless modes pinged to the
      boundary of a curvature, in an elliptical ring. An effective nonlinear
      Schrodinger equation along the azimuthal direction is derived by taking the
      transformation in the curvilinear coordinate of elliptical symmetry, which
      illustrates the formation of trapping potentials (barriers) along the semi-major
      (minor) axis. Our results demonstrate an alternative but efficient approach to
      access optical modes with a variety of inhomogeneous potentials.

PMID- 23546250
TI  - Optic axis determination based on polarization flipping effect induced by optical
      feedback.
AB  - For many materials, particularly biological tissues, optic axis orientation
      directly correlates with the materials performance, such as refractive index. In
      this Letter, a system measuring the optic axis azimuth was built using the laser
      feedback method that the polarization state of laser output is linearly polarized
      when optic axis azimuth is consistent with the initial direction of the laser
      polarization, otherwise elliptical polarization will be observed. The
      polarization state of the laser output is highly sensitive to the relative
      position of the optic axis and the initial direction of the laser polarization.
      This may be used to determine the optic axis azimuth of a material with a high
      precision.

PMID- 23546251
TI  - Reflectometry based on a frequency-shifted interferometer using sideband
      interference.
AB  - Frequency-shifted interferometry has shown great potential in optical fiber
      sensor multiplexing. In this letter, we propose and demonstrate a frequency
      shifted interferometer (FSI) based on sideband interference. Comparing with
      previous implementation of FSI based on a Sagnac interferometer, this scheme is
      much simpler and compact. By scanning the driving frequency of a LiNbO3 phase
      modulator in the range of 4.5-5.5 GHz, we demonstrate a spatial resolution of 0.1
      m, which is 50 times better than the previously reported results.

PMID- 23546252
TI  - Analysis of dissolved C2H2 in transformer oils using laser Raman spectroscopy.
AB  - We have developed a laser Raman spectroscopy technique for assessing the working
      conditions of transformers by measuring dissolved C2H2 gas concentrations present
      in transformer oils. A frequency doubled Q-switched Nd:YAG laser (532 nm) was
      used as a laser source, and Raman signals at ~1972 cm(-1) originating from C2H2
      gas dissolved in oil were detected. The results show that laser Raman
      spectroscopy is a useful alternative method for detecting transformer faults.

PMID- 23546253
TI  - Frequency noise in frequency swept fiber laser.
AB  - This Letter presents a measurement of the spectral content of frequency shifted
      pulses generated by a lightwave synthesized frequency sweeper. We found that each
      pulse is shifted in frequency with very high accuracy. We also discovered that
      noise originating from light leaking through the acousto- optical modulators and
      forward propagating Brillouin scattering appear in the spectrum.

PMID- 23546254
TI  - Large-area fiber-optic gyroscope on a multiplexed fiber network.
AB  - We describe a fiber-optic gyroscope based on the Sagnac effect, realized on a
      multiplexed telecom fiber network. Our loop encloses an area of 20 km2 and
      coexists with Internet data traffic. This Sagnac interferometer is capable of
      detecting signals that are larger than 10(-8) (rad/s)/?Hz, thus approaching ring
      laser gyroscopes without using a narrow-linewidth laser or sophisticated optics.
      The proposed gyroscope could be useful for seismic applications, opening new
      possibilities for this kind of optical fiber sensor.

PMID- 23546255
TI  - Lifetime-based measurement of stress using mechanoluminescence of SrAl2O4:Eu2+.
AB  - The stress and loading rate on disks of SrAl2O4:Eu mixed epoxy resin were
      measured by a lifetime-based method. The concentration of the mechanoluminescence
      (ML) phosphor and the excitation power did not affect the measured lifetime. The
      lifetime was proportional to the stress and was inversely proportional to the
      loading rate. The concentration, the excitation power, the stress, and the
      loading rate affected the peak intensity of ML, while previous work estimated the
      stress using the absolute intensity under well-controlled excitation and
      concentration conditions. The method used here can shorten the measurement time
      and enhance the practicality of a ML phosphor.

PMID- 23546256
TI  - Stable radio frequency phase delivery by rapid and endless post error
      cancellation.
AB  - We propose and demonstrate a phase stabilization method for transfer and
      downconvert radio frequency (RF) signal from remote antenna to center station via
      a radio-over-fiber (ROF) link. Different from previous phase-locking-loop-based
      schemes, we post-correct any phase fluctuation by mixing during the
      downconversion process at the center station. A rapid and endless operation is
      predicted. The ROF technique transfers the received RF signal directly, which
      will reduce the electronic complexity at the antenna end. The proposed scheme is
      experimentally demonstrated, with a phase fluctuation compression factor of about
      200. The theory and performance are also discussed.

PMID- 23546257
TI  - Beam quality improvement by joint compensation of amplitude and phase.
AB  - The M2 factor could be decomposed as amplitude term and phase term. A method to
      improve the beam quality of laser beams is proposed. In our method, the amplitude
      and phase of a laser beam are both compensated in order to improve the beam
      quality completely. In experiment, a laser amplifier is set to modulate the
      amplitude to Gaussian type, and a deformable mirror is used to compensate the
      phase aberration. The laser beam is well compensated by our method; the beam
      quality factor of the laser is improved from 1.7 to 1.1.

PMID- 23546258
TI  - Coherent detection of terahertz pulses via gas plasma induced by few-cycle laser
      pulses with fixed carrier envelope phase.
AB  - The time behavior of gas plasma induced by a few-cycle laser pulse with a
      simultaneously incident terahertz (THz) pulse is investigated via a transient
      photocurrent model. The results show that the second-harmonic intensity emitted
      from the gas plasma can well replicate the THz waveform if the laser pulse has a
      fixed carrier envelope phase. Based on these we propose a approach for THz
      coherent detection, which could realize coherent THz detection with very low
      laser energies and without a bias field, and may be very useful in some fields,
      such as remote THz sensing.

PMID- 23546259
TI  - Extended Mueller-Stokes description of polarization-mode transformation in
      linearly birefringent single-mode optical fibers.
AB  - We derive a more general version of the commonly known quasi-monochromatic
      Mueller matrix of a linearly birefringent single-mode optical fiber. In the
      matrix, the complex degree of self-coherence of the illuminating field is
      replaced by the normalized cross-correlation of a pair of any jointly stationary
      light disturbances associated with the eigenpolarization modes, where both
      modulus and phase of the cross correlation are included. This allows one to write
      polychromatic Mueller-Stokes equations of multisection systems transmitting any
      uniformly polarized stationary field. A way for handling arbitrary phase
      birefringence dispersion is also suggested.

PMID- 23546260
TI  - Temperature-dependent bulk viscosity of nitrogen gas determined from spontaneous
      Rayleigh-Brillouin scattering.
AB  - Values for the bulk viscosity eta(b) of molecular nitrogen gas (N2) were derived
      from spontaneous Rayleigh-Brillouin scattering at ultraviolet wavelengths
      (lambda=366.8 nm) and at a 90 degrees  scattering angle. Analysis of the
      scattering profiles yields values showing a linear increasing trend, ranging from
      eta(b)=0.7*10(-5) to 2.0*10(-5) kg.m(-1).s(-1) in the temperature interval from
      255 to 340 K. The present values, pertaining to hypersound acoustics at
      frequencies in the gigahertz domain, are found to be in agreement with results
      from acoustic attenuation experiments in N2 performed at megahertz frequencies.

PMID- 23546261
TI  - Mode locking at terahertz frequencies using a distributed Bragg reflector laser
      with a sampled grating.
AB  - We present a highly reproducible method of producing terahertz (THz) optical
      pulses using a class of mode-locked AlGaInAs/InP laser operating in the 1.55 MUm
      wavelength range. The device uses a sample grating distributed Bragg reflector to
      provide strong frequency selectivity at the mode-locked frequency while the
      distributed reflectors relax the fabrication tolerances and ensure the cavity can
      self adjust to being an integral number of mode-locked periods in length. The
      measured devices provide nearly transform-limited pulse trains at 640 GHz or 1.28
      THz with a high degree of controllability and operate with consistent performance
      over a wide range of drive conditions. Being low cost and compact sources of THz
      radiation, these lasers will open up many applications, including systems for
      high-speed optical communication and THz imaging.

PMID- 23546262
TI  - Two-step spatial phase-shifting radial shearing interferometery with circular
      gratings.
AB  - This Letter presents a simple radial shearing interferometery with circular
      gratings to measure the radial first-order derivative of arbitrary wavefront
      phase. Two spatial phase-shifted radial shearing interferograms can be
      simultaneously obtained by the system, and a two-step phase-shifting algorithm
      with arbitrary phase-shift value is proposed for phase retrieval. The measurement
      for spherical wave has shown the feasibility and validity, and the optical system
      is used to measure the radial first-order derivative of projection wavefront
      phase of a propane flame with plane incident wave.

PMID- 23546263
TI  - Exact surface-plasmon polariton solutions at a lossy interface.
AB  - Making use of a rigorous electromagnetic treatment, we demonstrate that the
      approximate results that are customarily employed for the analysis of a plasmon
      field at a metal/dielectric boundary are incorrect even in some situations in
      which they are supposed to hold. We show further that a new type of surface
      plasmon solution exists that does not follow from the standard approximate
      analysis. Energy-flow considerations indicate that the new polariton is a
      backward-propagating surface wave, as encountered in manmade structures. Our
      results are likely to find applications in metal/semiconductor and metamaterial
      plasmonics.

PMID- 23546264
TI  - Suspended Si ring resonator for mid-IR application.
AB  - In this Letter we fabricate and characterize suspended silicon (Si) waveguides
      and ring resonators for mid-infrared wavelength range. Both tunable laser and
      thermal tuning are used to cover wavelength ranges near 5.2 and 3.4 MUm. The
      loaded quality factors are estimated at 2700 at 5.2 MUm and 7900 at 3.4 MUm. Heat
      induced spectrum distortion is observed. Absorption loss is analyzed based on the
      spectrum distortion, simulation, and all-optical modulation. It is shown that
      main loss comes from scattering at surface and should be possible to reduce by
      improving fabrication process.

PMID- 23546265
TI  - Dual-band absorption of mid-infrared metamaterial absorber based on distinct
      dielectric spacing layers.
AB  - We present the simulation, fabrication, and characterization of a dual-band
      metamaterial absorber in the mid-infrared regime. Two pairs of circular-patterned
      metal-dielectric stacks are employed to excite the dual-band absorption peaks.
      Dielectric characteristics of the dielectric spacing layer determine energy
      dissipation in each resonant stack, i.e., dielectric or ohmic loss. By
      controlling material parameters, both two mechanisms are introduced into our
      structure. Up to 98% absorption is obtained at 9.03 and 13.32 MUm in the
      simulation, which is in reasonable agreement with experimental results. The
      proposed structure holds promise for various applications, e.g., thermal
      radiation modulators and multicolor infrared focal plane arrays.

PMID- 23546266
TI  - Simple turbulence measurements with azopolymer thin films.
AB  - A simple method to measure the influence on the laser beam propagation by a
      turbid medium is proposed. This measurement is based on the inscription of a
      surface relief grating (SRG) on an azopolymer thin film. The grating obtained
      with a single laser beam after propagation into a turbulent medium is perturbed
      and directly analyzed by a CCD camera through its diffraction pattern. Later, by
      scanning the surface pattern with an atomic force microscope, the inscribed SRG
      is analyzed with the Radon transform. This method has the advantage of using a
      single beam to remotely inscribe a grating detecting perturbations during the
      beam path. A method to evaluate the refractive index constant structure is
      developed.

PMID- 23546267
TI  - Number of independent parameters in the Mueller matrix representation of
      homogeneous depolarizing media.
AB  - In general the transmission of polarized light through a homogeneous depolarizing
      sample has motion-reversal symmetry because the response remains the same for
      light traveling in the opposite direction. As a consequence, the optical
      properties of a sample, characterized by the differential Mueller matrix, must be
      invariant upon motion reversal. This Letter shows that the 16 parameters of the
      differential Mueller matrix must therefore obey six conditions to satisfy this
      symmetry. This limits the number of independent parameters to 10. The 10
      elementary optical properties of a depolarizing homogeneous medium are defined
      and discussed.

PMID- 23546268
TI  - Characterization of homogenous depolarizing media based on Mueller matrix
      differential decomposition.
AB  - In a depolarizing medium in which the optical properties are uniformly
      distributed, the logarithm of the Mueller matrix can be used to calculate the
      differential Mueller matrix. From the differential Mueller matrix, the 10 optical
      properties of a homogeneous depolarizing medium are recovered. A modified
      calculation is introduced for media showing small time-irreversal depolarization
      events. The benefits of this method are illustrated in the determination of
      circular dichroism and circular birefringence of a nickel sulfate hexahydrate
      crystal from spectroscopic Mueller matrix measurements.

PMID- 23546269
TI  - Internally sensed optical phased array.
AB  - Extending phased array techniques to optical frequencies is challenging because
      of the considerably smaller wavelengths and the difficulty of stabilizing the
      optical path lengths of multiple emitters to this level of precision. This is
      especially true under real-world conditions where thermal and vibrational
      disturbances cause path length variations that are considerable in relation to
      the wavelength. Earlier attempts have relied on an external mechanism to sense
      and compensate for any unwanted variations in the outgoing beams. Here we propose
      and demonstrate a method that does not rely on any external components. The
      method combines a pseudo-random noise phase modulation scheme together with
      conventional heterodyne interferometry to simultaneously measure phase variations
      between emitters. This information is then used to control the relative phases
      between the emitters and compensate for any unwanted disturbance. Experimental
      results are presented that support the viability of this design.

PMID- 23546270
TI  - Eutectic epsilon-near-zero metamaterial terahertz waveguides.
AB  - We present and analyze the unique phenomena of enhanced THz transmission through
      a subwavelength LiF dielectric rod lattice embedded in an epsilon-near-zero KCl
      host. Our experimental results in combination with theoretical calculations show
      that subwavelength waveguiding of terahertz radiation is achieved within an
      alkali-halide eutectic metamaterial as result of the coupling of Mie-resonance
      modes arising in the dielectric lattice.

PMID- 23546271
TI  - Spatiotemporal characterization of ultrabroadband Airy pulses.
AB  - We present experimental results of a full spatiotemporal characterization of an
      optical system for ultrabroadband Airy pulse generation with a liquid-crystal-on
      silicon spatial light modulator. Measurements with a few micrometer spatial and
      almost one-wave-cycle temporal resolution were performed using a white light
      spatial spectral interferometry setup based on the SEA TADPOLE ultrashort pulse
      characterization technique. The results were compared with the theoretical model
      for Airy pulse propagation.

PMID- 23546272
TI  - Ion-exchanged Tm3+:glass channel waveguide laser.
AB  - Continuous wave laser action around 1.9 MUm has been demonstrated in a Tm(3+)
      doped germanate glass channel waveguide laser fabricated by ion-exchange. Laser
      action was observed with an absorbed power threshold of only 44 mW and a slope
      efficiency of up to 6.8% was achieved. Propagation loss at the lasing wavelength
      was measured to be 0.3 dB/cm. We believe this to be the first ion-exchanged
      Tm(3+)-doped glass waveguide laser.

PMID- 23546273
TI  - Use of photonic crystal cavities for temporal differentiation of optical signals.
AB  - We show that general-form optical cavities are able to perform the temporal
      differentiation of optical signals. Analytical relationships to account for the
      scattering losses for such a cavity's characteristics are deduced on the basis of
      temporal coupled-mode theory. A compact nanocavity-aided differentiator based on
      a ridge photonic crystal waveguide is designed.

PMID- 23546274
TI  - Brillouin/Raman compensation of the Kerr-effect-induced bias in a nonlinear ring
      laser gyroscope.
AB  - In this Letter, the beat frequency at rest of a ring laser gyroscope with
      nonlinear effects is discussed in detail. Even without an additional intensity
      stabilizing system, the random nullshift bias induced by the Kerr effect is
      compensated by the phase shift associated with the stimulated Brillouin/Raman
      scattering. And the nonlinear stimulated scattering also serves as the gain
      mechanism of the gyroscope. And thus the influence of the fluctuation of the
      injected pump intensity on the beat frequency is eliminated.

PMID- 23546275
TI  - Milliwatt-level frequency combs in the 8-14 MUm range via difference frequency
      generation from an Er:fiber oscillator.
AB  - We report on the generation of mid-infrared (mid-IR) pulses with a maximum
      average optical power of 4 mW and wide tunability in the 8-14 MUm range via
      difference frequency generation (DFG) in GaSe from an Er:fiber laser oscillator.
      The DFG process is seeded with self-frequency shifted Raman solitons that are
      shown to be phase coherent within the whole tuning range, from 1.76 to 1.93 MUm.
      Interference measurements between adjacent pulses at the idler wavelengths attest
      coherence transfer to the mid-IR.

PMID- 23546276
TI  - Formation of temperature dependable holographic memory using holographic polymer
      dispersed liquid crystal.
AB  - Grating devices using photosensitive organic materials play an important role in
      the development of optical and optoelectronic systems. High diffraction
      efficiency and polarization dependence achieved in a holographic polymer
      dispersed liquid crystal (HPDLC) grating are expected to provide polarization
      controllable optical devices, such as the holographic memory for optically
      reconfigurable gate arrays (ORGAs). However, the optical property is affected by
      the thermal modulation around the transition temperature (T(ni)) that the liquid
      crystal (LC) changes from nematic to isotropic phases. The temperature dependence
      of the diffraction efficiency in HPDLC grating is discussed with two types of LC
      composites comprised of isotropic and LC diacrylate monomers. The holographic
      memory formed by the LC and LC diacrylate monomer performs precise reconstruction
      of the context information for ORGAs at high temperatures more than 150 degrees
      C.

PMID- 23546277
TI  - Multiple side-band generation for two-frequency components injected into a
      tapered amplifier.
AB  - We have experimentally studied multiple side-band generation for two-frequency
      components injected into a tapered amplifier (TA) and demonstrated its effects on
      atomic laser cooling. A heterodyne frequency-beat measurement and a Fabry-Perot
      interferometer have been applied to analyze the side-band generation with
      different experimental parameters, such as frequency difference, injection laser
      power, and TA current. In laser-cooling potassium40 and potassium41 with
      hyperfine splitting of 1.3 GHz and 254 MHz, respectively, the side-band
      generation with a small frequency difference has a significant effect on the
      number of trapped atoms.

PMID- 23546278
TI  - Shifted dispersion-induced radio-frequency fading in microwave photonic filters
      using a dual-input Mach-Zehnder electro-optic modulator.
AB  - A simple microwave photonic processor structure with single passband response,
      and widely tunable capability, is demonstrated. It is based on the principle of
      shifted dispersion-induced radio-frequency (RF) fading by using a dual-input Mach
      Zehnder electro-optic modulator (EOM) that is fed from a broadband optical source
      with unbalanced input fiber lengths into the upper and lower arms of the EOM, in
      combination with a dispersive medium. This topology consequently produces a
      spectral response equivalent to the curve of the dispersion-induced RF fading
      that is shifted from the conventional baseband location to high frequencies.
      Therefore, an equivalent single passband is formed without the requirement of the
      conventional tap coefficients. Experimental results verify the structure and
      demonstrate a continuously tunable microwave filter exhibiting shape invariance
      and a single passband. In addition, the filter response sidelobe suppression is
      also significantly improved by applying a Gaussian windowed profile to the
      broadband optical source.

PMID- 23546279
TI  - Implementation of wavelength reusing upstream service based on distributed
      intensity conversion in ultrawideband-over-fiber system.
AB  - We propose and demonstrate a simple scheme for generating the ultrawideband (UWB)
      signals and reusing the wavelength for upstream service simultaneously by using a
      distributed polarization modulation-to-intensity modulation convertor. Through
      adjusting the static phase difference between transverse electric and transverse
      magnetic modes of the optical carrier (OC) and the angle between the polarization
      direction of the OC and the principal axis of the polarizers, the UWB doublet
      like signals were generated. Meanwhile, the error-free transmission of the
      upstream signals with bit rate of 1.25 Gbit/s over 10 km fiber is achieved. The
      power penalty resulting from the interference of downstream signals is less than
      0.3 dB.

PMID- 23546280
TI  - Fiber coupler for mode selection and high-efficiency pump coupling.
AB  - A pump/signal fiber coupler with functions of pump light coupling and high-order
      mode suppression is reported. This coupler is composed of pump fibers and a
      double-clad fiber (DCF) with high pump-coupling efficiency. The core of DCF is
      microdeformed in the coupling region, which serves mode selection. Theoretical
      analysis and experimental results verify these functions. In the experiment, the
      pump-coupling and signal-transmitting efficiency of the coupler were ~98% and
      ~96%, respectively. This coupler can prevent mode distortion with fundamental
      mode launching, and improve the fiber laser beam quality with high-order-mode
      launching.

PMID- 23546281
TI  - Complete spatial characterization of an optical wavefront using a variable
      separation pinhole pair.
AB  - We present a technique for measuring the transverse spatial properties of an
      optical wavefront. Intensity and phase profiles are recovered by analysis of a
      series of interference patterns produced by the combination of a scanning X
      shaped slit and a static horizontal slit; the spatial coherence may be found from
      the same data. We demonstrate the technique by characterizing high harmonic
      radiation generated in a gas cell, however the method could be extended to a wide
      variety of light sources.

PMID- 23546282
TI  - Healing-block-assisted quasi-phase matching.
AB  - A quasi-phase matching (QPM) structure based on phase correction by inserting a
      "healing block" (HB) of length d(HB) into M regular domains of constant length d
      is proposed to enhance the nonlinear conversion efficiency when the first-order
      QPM domain length d1 is too short to be reliably fabricated. Second-harmonic
      conversion efficiency 4.69 times higher than that of a third-order QPM grating
      has been experimentally demonstrated by using HB-QPM where all the domains are
      longer than 1.08d1.

PMID- 23546283
TI  - Infrared perfect absorber based on nanowire metamaterial cavities.
AB  - An infrared perfect absorber based on a gold nanowire metamaterial cavities array
      on a gold ground plane is designed. The metamaterial made of gold nanowires
      embedded in an alumina host exhibits an effective permittivity with strong
      anisotropy, which supports cavity resonant modes of both electric dipole and
      magnetic dipole. The impedance of the cavity modes matches the incident plane
      wave in free space, leading to nearly perfect light absorption. The incident
      optical energy is efficiently converted into heat so that the local temperature
      of the absorber will increase. Results show that the designed absorber is
      polarization-insensitive and nearly omnidirectional for the incident angle.

PMID- 23546284
TI  - Singular diffraction-free surface plasmon beams generated by overlapping phase
      shifted sources.
AB  - We propose and experimentally demonstrate the singular surface plasmon beam that
      presents a dark channel generated by a point dislocation and a long diffraction
      free propagation distance up to 70lambda(sp). The singular surface beam is the
      result of the interference of two surface plasmon polariton (SPP) plane waves,
      which are launched by two coupling gratings with lateral displacement. An
      aperture-type near-field scanning optical microscope is used to map the intensity
      distribution of the singular SPP waves. The propagating point dislocation
      embedded in the beam is shown by full-wave calculations and is later verified by
      near-field interference in the experiment.

PMID- 23546285
TI  - Broadband supercontinuum generation in As2Se3 chalcogenide wires by avoiding the
      two-photon absorption effects.
AB  - We report the generation of a broadband supercontinuum (SC) spanning from 1260 to
      2200 nm using a 10 cm long As2Se3 chalcogenide (ChG) wire pumped at a wavelength
      of 1550 nm. Such a wide SC in As2Se3 is obtained by avoiding the effects of two
      photon absorption normally observed at a wavelength of 1550 nm. For this purpose,
      the pump soliton is initially self-frequency shifted toward longer wavelength by
      means of the Raman effect in standard silica fiber before being launched into the
      ChG wire for spectral broadening.

PMID- 23546286
TI  - A model of the central regulatory system for cough reflex.
AB  - Cough is an important defensive reflex that eliminates particles and secretions
      from the airways and protects the lower airways from the aspiration of foreign
      materials. Although the classical cough center is thought to be situated in or
      around the nucleus tractus solitarius (NTS) of the brainstem, our understanding
      of its profile is still incomplete. Accumulating evidence suggests a new concept
      of the central regulatory system for cough reflex. The cough pattern generator in
      the brainstem appears to be identical to the respiratory pattern generator and to
      function by reshaping of the discharge pattern of respiratory neurons. The
      generated cough motor task is transmitted to spinal motoneurons through the
      descending respiratory pathways. The cough-gating mechanism receives the
      peripheral tussigenic information through the relay neurons in the NTS and
      activates such a functionally flexible pattern generator by producing triggering
      signals. This review focuses on the cough-gating neurons that constitute the
      gating mechanism and play a crucial role in the generation of cough reflex.

PMID- 23546287
TI  - Cetylpyridinium chloride inhibits receptor activator of nuclear factor-kappaB
      ligand-induced osteoclast formation.
AB  - Osteoclasts are responsible for bone erosion in diseases as diverse as
      osteoporosis, periodontitis, and rheumatoid arthritis. Antiseptic products have
      received recent attention as potential therapeutic and preventive drugs in human
      disease. The purpose of this study was to investigate the effect of the
      antiseptic cetylpyridinium chloride (CPC) on osteoclast formation using mouse
      bone marrow-derived macrophages (BMMs). CPC inhibited receptor activator of
      nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclast formation in a dose
      dependent manner without causing cytotoxicity. The mRNA expression of cathepsin
      K, calcitonin receptor (CTR), and Prdm1 in osteoclasts was reduced by CPC. In
      experiments to elucidate its mechanism of action, CPC was found to suppress RANKL
      induced expression of c-Fos and nuclear factor of activated T cells (NFATc1),
      transcription factors that are essential for osteoclast differentiation. CPC also
      inhibited RANKL-induced activation of extracellular signal-regulated kinase (ERK)
      and NF-kappaB and expression of cyclooxygenase (COX)-2. These results
      collectively suggest that CPC inhibits osteoclast differentiation by suppressing
      the activation of ERK and NF-kappaB and reducing the expression of COX-2, c-Fos,
      and NFATc1. CPC may therefore be a useful drug in the prevention of bone loss.

PMID- 23546288
TI  - Effects of astragaloside IV on action potentials and ionic currents in guinea-pig
      ventricular myocytes.
AB  - Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus
      membranaceus, which has various actions on the cardiovascular system. However,
      its electrophysiological mechanisms are not clear. In the present study, we
      investigated the effects of AS-IV on action potentials and membrane currents
      using the whole-cell patch clamp technique in isolated guinea-pig ventricular
      myocytes. AS-IV prolonged the action potential duration (APD) at all three tested
      concentrations. The peak effect was achieved with 1*10(-6) M, at which
      concentration AS-IV significantly prolonged the APD at 95% repolarization from
      313.1+/-38.9 to 785.3+/-83.7 ms. AS-IV at 1*10(-6) M also enhanced the inward
      rectifier K(+) currents (I(K1)) and inhibited the delayed rectifier K(+) currents
      (I(K)). AS-IV (1*10(-6) M) strongly depressed the peak of voltage-dependent
      Ca(2+) channel current (I(CaL)) from -607.3+/-37.5 to -321.1+/-38.3 pA. However,
      AS-IV was not found to affect the Na(+) currents. Taken together, AS-IV prolonged
      APD of guinea-pig ventricular myocytes, which might be explained by its
      inhibition of I(K). AS-IV also influences Ca(2+) signaling through suppressing
      ICaL.

PMID- 23546289
TI  - Changes in small heat shock proteins HSPB1, HSPB5 and HSPB8 in mitochondria of
      the failing heart following myocardial infarction in rats.
AB  - The mechanisms underlying mitochondrial impairment in the failing heart are not
      yet clearly defined. In the present study, we examined the involvement of changes
      in small heat shock proteins (HSPs) such as HSPB1, HSPB5 and HSPB8 in
      mitochondrial dysfunction of the failing heart. Hemodynamic parameters of rats
      with myocardial infarction at the 2nd and 8th weeks (2W- and 8W-) after coronary
      artery ligation (CAL) were measured. The 8W-CAL rats, but not the 2W-CAL ones,
      showed the signs of the chronic heart failure concomitant with a reduced
      mitochondrial oxygen consumption rate. In the mitochondrial fraction prepared
      from the heart of the 2W-CAL animals, the contents of small HSPs and
      phosphorylated small HSPs were increased, suggesting that these increases
      contributed to the preservation of the mitochondrial energy-producing ability. In
      the failing heart, HSPB1 and HSPB8 contents and phosphorylated small HSP contents
      in the mitochondrial fraction were decreased, suggesting that a reduction in
      mitochondrial translocation of these small HSPs led to impaired mitochondrial
      energy-producing ability. To further define the submitochondrial locations of
      these small HSPs, we performed mitochondrial subfractionation. The contents of
      small HSPs in the 2W-CAL rats were increased in the mitochondrial inner-membrane
      fraction, whereas those of the 8W-CAL rats were reversed to those of the control
      animals. These findings suggest that small HSPs, at least in part, play an
      important role in the development of the impaired mitochondrial energy-producing
      ability that leads to heart failure after a myocardial infarction.

PMID- 23546290
TI  - Nobiletin induces inhibitions of Ras activity and mitogen-activated protein
      kinase kinase/extracellular signal-regulated kinase signaling to suppress cell
      proliferation in C6 rat glioma cells.
AB  - Ras, a small G-protein, physiologically directs cell proliferation and cell cycle
      via regulation of mitogen-activated protein kinase kinase (MEK)/extracellular
      signal-regulated kinase (ERK) signaling cascade. Dysregulation of Ras/MEK/ERK
      signaling has been reported to cause tumorigenesis and gliomas. Nobiletin, a
      citrus flavonoid, has been shown to have anti-tumor cells action. However, it
      remains elusive whether nobiletin could affect Ras activity. In this study, we
      provide the first evidence that nobiletin suppresses the proliferation by
      inhibiting Ras activity in C6 glioma cells, a rat glioma cell line. First, Ras
      pull-down assay showed that nobiletin inhibits Ras activity in a concentration
      dependent manner in C6 cells. Second, farnesyltransferase inhibitor I, a Ras
      inhibitor, and U0126, a MEK inhibitor, induced an inhibition of the cell
      proliferation in C6 cells, while the cell proliferation was inhibited by
      nobiletin as well. Third, western blotting revealed that nobiletin showed
      inhibitory effects on MEK and ERK phopsphorylation levels in a concentration
      dependent manner. Finally, such an inhibitory effect on the level of ERK
      phosphorylation by nobiletin was appreciably prevented by Go6976, a selective
      inhibitor of conventional protein kinase Cs (PKCs) showing Ca(2+)-sensitivity,
      while GF109203X, a general inhibitor for PKCs, and BAPTA, a cell-permeable Ca(2+)
      chelator, to a lesser extent, suppressed a reduction of the phosphorylation.
      These findings suggest that the proliferation of C6 cells is Ras- and MEK/ERK
      signaling-dependent, and that nobiletin suppresses the cell proliferation by
      inhibiting Ras activity and MEK/ERK signaling cascade probably via a Ca(2+)
      sensitive PKC-dependent mechanism. Thus, the natural compound has potential to be
      a therapeutic agent for glioma.

PMID- 23546291
TI  - Effects of cyanamide, an aldehyde dehydrogenase type 2 inhibitor, on glyceryl
      trinitrate- and isosorbide dinitrate-induced vasodilation in rabbit excised aorta
      and in anesthetized whole animal.
AB  - The contribution of aldehyde dehydrogenase type 2 (ALDH2) to bioactivation of
      glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN) was systematically
      examined in excised rabbit aorta and anesthetized whole animal with cyanamide, an
      ALDH2 inhibitor. In excised aortic preparation, the degree of inhibition by
      cyanamide in GTN-induced vasorelaxation (concentration ratio, calculated as
      EC(50) in the presence of cyanamide/EC(50) in the absence of cyanamide; 5.61) was
      twice that in ISDN-induced relaxation (2.78). However, the degree of inhibition
      by cyanamide, as assessed by the dose ratio (as described above, but calculated
      with doses) in anesthetized rabbits was 2.29 in GTN-induced hypotension (assessed
      by area under the curve (AUC) of 50 mmHg.min) and 7.68 in ISDN-induced
      hypotension. Thus, the inhibitor was 3 times more potent in ISDN-induced
      hypotension, a finding in conflict with to that obtained in excised aortic
      preparation. The rate of increase in plasma nitrite (NO(2)(-)) concentration at
      certain hypotensive effect (50 mmHg.min of AUC) in the presence and absence of
      cyanamide (DeltaNO(2)(-) ratio) was larger in ISDN-induced hypotension (15.01)
      than in GTN-induced hypotension (3.28). These results indicate that the
      bioactivation pathway(s) of GTN is ALDH2-dependent in aortic smooth muscle, while
      ADLH2-independent mechanism(s) largely take place in the whole body. In contrast,
      the activation mechanism(s) of ISDN is largely ALDH2-dependent in both aortic
      smooth muscle and whole body. Plasma NO(2)(-) may be derived from pathways other
      than the cyanamide-sensitive metabolic route.

PMID- 23546292
TI  - The effect of sex hormones on peroxisome proliferator-activated receptor gamma
      expression and activity in mature adipocytes.
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma plays a major role in the
      regulation of lipid and carbohydrate metabolism. Pioglitazone is a PPARgamma
      agonist that is widely used for the treatment of type 2 diabetes mellitus.
      However, female patients have been reported to experience stronger efficacy and
      adverse effects than male patients. This study evaluated the effects of sex
      hormones on PPARgamma expression and activity in adipocytes. Mouse 3T3-L1
      preadipocytes were used after being grown into matured adipocytes. The sex
      hormones 17beta-estradiol (E2), testosterone (T), or 5alpha-androstan-17beta-ol-3
      one (dihydrotestosterone; DHT) were added to the matured adipocytes and the cells
      were then maintained for short (24-72 h) or long (1- or 2-weeks) periods. E2
      significantly upregulated PPARgamma protein expression in a concentration
      dependent manner after extended exposure, whereas T and DHT did not have such an
      effect. When cells were co-treated with pioglitazone and E2, PPARgamma protein
      expression significantly increased in an E2-dependent manner, whereas this
      expression seemed to be reduced by pioglitazone mono-treatment and co-treatment
      with DHT at higher concentrations. The secretion levels of adiponectin protein, a
      major indicator of PPARgamma activity, were significantly decreased by DHT, but
      were not affected by E2. Finally a luciferase assay was performed using a PPAR
      response element-Luk reporter gene. Transcriptional activity was not changed by
      any of single sex hormone treatment, but was significantly downregulated by co
      treatment with pioglitazone and DHT. Taken together, our results suggest that sex
      hormones may influence PPARgamma expression and function, which may explain the
      observed sex-specific different effect of pioglitazone.

PMID- 23546293
TI  - Protective effects of apomorphine against zinc-induced neurotoxicity in cultured
      cortical neurons.
AB  - There is evidence that excessive zinc (Zn(2+)) release from presynaptic terminals
      following brain injuries such as ischemia and severe epileptic seizures induces
      neuronal cell death. Apomorphine (Apo), a dopamine receptor agonist, has been
      shown to have pleiotropic biological functions. In this study, we investigated
      whether Apo protects cultured cortical neurons from neurotoxicity provoked by
      excessive Zn(2+) exposure. Pretreatment with Apo dose- and time-dependently
      ameliorated Zn(2+) neurotoxicity. In addition, pretreatment with Apo prevented
      intracellular nicotinamide adenine dinucleotide (NAD(+)) and ATP depletion caused
      by Zn(2+) exposure. Dopamine receptor antagonists did not influence Apo
      protection against Zn(2+) neurotoxicity. Apo is shown to be autoxidized to
      produce oxidized products such as reactive oxygen species and quinones. N
      Acetylcysteine, a thiol compound, partially reduced Apo protection. Entry of
      Zn(2+) into neurons is thought to be a critical step of Zn(2+) neurotoxicity.
      Interestingly, we found that pretreatment with Apo decreased elevation of
      intracellular Zn(2+) levels after Zn(2+) exposure and induced mRNA expression of
      the zinc transporter ZnT1, which transports intracellular Zn(2+) out of cells,
      and metallothionein. Taken together, these results suggest that the protective
      effects of Apo are regulated, at least in part, by its oxidized products, and
      preventing intracellular accumulation of Zn(2+) contributes to Apo protection
      against Zn(2+) neurotoxicity.

PMID- 23546294
TI  - In vivo evaluation of a radiogallium-labeled bifunctional radiopharmaceutical, Ga
      DOTA-MN2, for hypoxic tumor imaging.
AB  - On the basis of the findings obtained by X-ray crystallography of Ga-DOTA
      chelates and the drug design concept of bifunctional radiopharmaceuticals, we
      previously designed and synthesized a radiogallium-labeled DOTA chelate
      containing two metronidazole moieties, (67)Ga-DOTA-MN2, for hypoxic tumor
      imaging. As expected, (67)Ga-DOTA-MN2 exhibited high in vivo stability, although
      two carboxyl groups in the DOTA skeleton were conjugated with metronidazole
      moieties. In this study, we evaluated (67/68)Ga-DOTA-MN2 as a nuclear imaging
      agent for hypoxic tumors. (67)Ga-labeling of DOTA-MN2 with (67)GaCl(3) was
      achieved with high radiochemical yield (>85%) by 1-min of microwave irradiation
      (50 W). The pharmacokinetics of (67)Ga-DOTA-MN2 were examined in FM3A tumor
      bearing mice, and compared with those of (67)Ga-DOTA-MN1 containing one
      metronidazole unit and (67)Ga-DOTA. Upon administration, (67)Ga-DOTA-MN2
      exhibited higher accumulation in the implanted tumors than (67)Ga-DOTA. Tumor-to
      blood ratios of (67)Ga-DOTA-MN2 were about two-fold higher than those of (67)Ga
      DOTA-MN1. Autoradiographic analysis showed the heterogeneous localization of
      (67)Ga-DOTA-MN2 in the tumors, which corresponds to hypoxic regions suggested by
      well-established hypoxia marker drug, pimonidazole. Furthermore, in positron
      emission tomography (PET) study, the tumors of mice administered (68)Ga-labeled
      DOTA-MN2 were clearly imaged by small-animal PET at 1 h after administration.
      This study demonstrates the potential usefulness of (67/68)Ga-DOTA-MN2 as a
      nuclear imaging agent for hypoxic tumors and suggests that two functional
      moieties, such as metronidazole, can be conjugated to radiogallium-DOTA chelate
      without reducing the complex stability. The present findings provide useful
      information about the chemical design of radiogallium-labeled
      radiopharmaceuticals for PET and single photon emission computed tomography
      (SPECT) studies.

PMID- 23546296
TI  - High-throughput and sensitive assay for amphotericin B interaction with lipid
      membrane on the model membrane systems by surface plasmon resonance.
AB  - In the present study, we developed a high-throughput and sensitive assay for
      interactions of amphotericin B (AmB) with two model lipid membranes, which
      mimicked mammal cell membrane and fungal membrane using surface plasmon resonance
      (SPR). The binding kinetics of AmB to the membrane could be analyzed by multiple
      sensorgrams obtained at different AmB concentrations, indicating that the binding
      properties could be clarified for an approximately 7-fold concentration range.
      AmB showed an approximately 18-fold higher affinity for ergosterol-containing
      membrane than for cholesterol-containing membrane. We also optimized the
      procedure for the reproducible immobilization of liposome containing the sterols
      and the estimation of binding kinetics of AmB to the lipid membranes, and the
      sensitivity of AmB to membrane interaction was 20-fold higher, compared with the
      reported method. The throughput of the established method for the binding
      kinetics characterization was calculated to be 10 compounds a day. The results
      demonstrate that the established SPR method could be a valuable tool for
      predicting selective binding to sterol-containing membranes.

PMID- 23546295
TI  - Antioxidant action of ellagic acid ameliorates paraquat-induced A549
      cytotoxicity.
AB  - Ellagic acid (EA) is a natural dietary polyphenol whose benefits in a variety of
      diseases shown in epidemiological and experimental studies involve anti
      inflammation, anti-proliferation, anti-angiogenesis, anti-carcinogenesis and anti
      oxidation properties. This study aimed to evaluate the effect of EA against
      paraquat (PQ)-induced oxidative stress. PQ decreased the viability of A549 cells
      in dose- and time-dependent manners, which was associated with the massive
      generation of reactive oxygen species (ROS). However, cell viability was
      significantly recovered by the treatment of EA, from 47.01+/-1.59% to 66.04+/
      2.84%. The release of lactate dehydrogenase (LDH) was also decreased with the
      treatment of EA in PQ-treated A549 cells. EA induced the level of expression and
      activation of nuclear factor-erythroid 2-related factor (Nrf2) and its target
      cytoprotective and antioxidant genes, heme oxygenase-1 (HO-1) and quinone
      oxidoreductase 1 (NQO1). The antioxidant potential of EA might be directly
      correlated with the increased expression of HO-1 and NQO1, whose expression may
      have surmounted the oxidative stress generated by PQ. Notably, EA treatment
      significantly reduced the levels of biochemical markers as lipid peroxidation,
      reduced the intracellular ROS level, and surmounted total glutathione level in
      A549 cells. Data indicate that the antioxidant and cytoprotective properties of
      EA reduce PQ-induced cytotoxicity in human alveolar A549 cells.

PMID- 23546297
TI  - Peptide structure modifications: effect of radical species generated by
      controlled gamma ray irradiation approach.
AB  - The present work aimed at evaluating the radiolysis effect upon a set of
      peptides, most of them involved in physiological functions. To generate reactive
      radical species, a Co(60) source (up to 15 kGy) was used for controlled gamma
      irradiation of some peptide solutions including derivatives attaching the stable
      free radical Toac (2,2,6,6-tetramethypiperidine-1-oxyl-4-amino-4-carboxylic
      acid). Regardless of the peptide sequence, a nonlinear and progressive
      degradation of a total of nine peptides was detected. The results were
      interpreted in the light of the half-life dose (D(1/2)) parameter which
      represents the dose necessary for 50% peptide structure degradation. The
      vasoactive angiotensin II (AngII)'s analogue Ang-(1-7) showed greater stability
      towards gamma ray radiation than bradykinin (BK), Toac(0)-BK, Pro(4)-BK (D(1/2)
      around 4 and 2 kGy, respectively) which decreased to about 0.5-1.0 kGy in the
      case of acetyl-alpha-melanocyte-stimulating hormone (Ac-alpha-MSH) and substance
      P (SP). In terms of peptide structural modifications, the data acquired from
      different analytical methods suggested a Phe to Tyr (or its ortho and/or meta
      isomers) transformation as a consequence of the hydroxyl moiety insertion.
      Noteworthy, this effect seemed to be position-dependent as only Phe located at or
      near the C-terminal portion seemed to display this transformation. In contrast,
      Met is comparatively more easily oxidized, thus allowing to conclude that gamma
      irradiation may induce a complex position and/or sequence-dependent effect on
      peptides. As previously applied for BK, some irradiated peptides were submitted
      to their by-products purification, indeed a complementary target of the present
      approach for development of uncommon analogues for further structure-function
      investigation.

PMID- 23546298
TI  - Plasma and serum from nonfasting men and women differ in their lipidomic
      profiles.
AB  - Biomarkers will play important roles in disease diagnosis, drug development, and
      the proper use of drugs. Blood is considered the best biofluid for biomarker
      research because it is easy to access and a wealth of data are available.
      However, previous studies revealed that several ionic metabolites showed
      different levels (including presence or absence) in plasma and serum. Thus,
      attention should be paid to selecting the best biofluid for biomarker
      exploration. Many lipid molecules have biological significance and thus would be
      candidate biomarkers. However, no comprehensive study revealing differences in
      lipid metabolite levels between plasma and serum has been undertaken.
      Furthermore, gender differences have not been reported. To clarify the difference
      in the levels of lipid metabolites between human plasma and serum from both
      genders, we performed lipid metabolomic analysis using liquid chromatography-mass
      spectrometry-based systems for phospholipids (PLs), lysoPLs, sphingomyelins,
      ceramides and oxidative fatty acids. Our results revealed that most of the lipid
      metabolites were present at similar levels in plasma and serum and in males and
      females. However, several oxidative fatty acid metabolites showed differences. Of
      the metabolites related to clotting processes, three showed higher levels in
      serum than in plasma, and three were detected only in serum. Furthermore, four
      metabolites were present at different levels between males and females, and two
      were detected only in males. Thus, attention should be paid to the selection of
      plasma or serum when utilizing these lipid metabolites as biomarkers.

PMID- 23546299
TI  - Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune
      responses in cancer patients.
AB  - Oncolytic adenoviruses and certain chemotherapeutics can induce autophagy and
      immunogenic cancer cell death. We hypothesized that the combination of oncolytic
      adenovirus with low-dose temozolomide (TMZ) is safe, effective, and capable of
      inducing antitumor immune responses. Metronomic low-dose cyclophosphamide (CP)
      was added to selectively reduce regulatory T-cells. Preclinically, combination
      therapy inhibited tumor growth, increased autophagy, and triggered immunogenic
      cell death as indicated by elevated calreticulin, adenosine triphosphate (ATP)
      release, and nuclear protein high-mobility group box-1 (HMGB1) secretion. A total
      of 41 combination treatments given to 17 chemotherapy-refractory cancer patients
      were well tolerated. We observed anti- and proinflammatory cytokine release,
      evidence of virus replication, and induction of neutralizing antibodies. Tumor
      cells showed increased autophagy post-treatment. Release of HMGB1 into serum--a
      possible indicator of immune response--increased in 60% of treatments, and seemed
      to correlate with tumor-specific T-cell responses, observed in 10/15 cases
      overall (P = 0.0833). Evidence of antitumor efficacy was seen in 67% of evaluable
      treatments with a trend for increased survival over matched controls treated with
      virus only. In summary, the combination of oncolytic adenovirus with low-dose TMZ
      and metronomic CP increased tumor cell autophagy, elicited antitumor immune
      responses, and showed promising safety and efficacy.

PMID- 23546301
TI  - Core-shell VO2@TiO2 nanorods that combine thermochromic and photocatalytic
      properties for application as energy-saving smart coatings.
AB  - Vanadium dioxide (VO2) is a Mott phase transition compound that can be applied as
      a thermochromic smart material for energy saving and comfort, and titanium
      dioxide (TiO2) is a well-known photocatalyst for self-cleaning coatings. In this
      paper, we report a VO2@TiO2 core-shell structure, in which the VO2 nanorod core
      exhibits a remarkable modulation ability for solar infrared light, and the TiO2
      anatase shell exhibits significant photocatalytic degradation of organic dye. In
      addition, the TiO2 overcoating not only increased the luminous transmittance of
      VO2 based on an antireflection effect, but also modified the intrinsic colour of
      VO2 films from yellow to light blue. The TiO2 also enhanced the chemical
      stability of VO2 against oxidation. This is the first report of such a single
      nanoparticle structure with both thermochromic and photocatalytic properties that
      offer significant potential for creating a multifunctional smart coating.

PMID- 23546300
TI  - TALEN-based gene correction for epidermolysis bullosa.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is characterized by a
      functional deficit of type VII collagen protein due to gene defects in the type
      VII collagen gene (COL7A1). Gene augmentation therapies are promising, but run
      the risk of insertional mutagenesis. To abrogate this risk, we explored the
      possibility of using engineered transcription activator-like effector nucleases
      (TALEN) for precise genome editing. We report the ability of TALEN to induce site
      specific double-stranded DNA breaks (DSBs) leading to homology-directed repair
      (HDR) from an exogenous donor template. This process resulted in COL7A1 gene
      mutation correction in primary fibroblasts that were subsequently reprogrammed
      into inducible pluripotent stem cells and showed normal protein expression and
      deposition in a teratoma-based skin model in vivo. Deep sequencing-based genome
      wide screening established a safety profile showing on-target activity and three
      off-target (OT) loci that, importantly, were at least 10 kb from a coding
      sequence. This study provides proof-of-concept for TALEN-mediated in situ
      correction of an endogenous patient-specific gene mutation and used an unbiased
      screen for comprehensive TALEN target mapping that will cooperatively facilitate
      translational application.

PMID- 23546302
TI  - High permeability and salt rejection reverse osmosis by a zeolite nano-membrane.
AB  - The possibility of employing a zeolite nano-membrane for seawater desalination is
      studied using comprehensive molecular dynamics simulations. Two types of zeolite
      with different wetting properties, the hydrophilic FAU and hydrophobic MFI, are
      used as the reverse osmosis (RO) membrane. Both can reach nearly 100% rejection
      of salt ions, and when the membrane thickness is smaller than 3.5 nm, the
      permeability is about 2 * 10(-9) m Pa(-1) s(-1), which is two orders of magnitude
      higher than that of the commercial state-of-the-art RO membrane. The relation
      between the permeability and thickness of the zeolite membrane is studied through
      the pressure drop-flux dependence. The pressure drop is linearly dependent on the
      thickness of the zeolite membrane. As the thickness approaches nanoscale, the end
      effect of water molecules entering the zeolite membrane has apparent influence on
      the pressure drop. For the FAU membrane the hydrophilicity can assist the water
      molecules entering the nanopore with reduced pressure drop, while for the
      hydrophobic MFI zeolite additional pressure drop arises from the capillary
      resistance. In order to sustain the pressure drop during desalination, the
      nanoscale zeolite membrane should be placed on a porous substrate and the ratio
      of the thickness of the nano-membrane to the radius of the supporting pore in the
      substrate should be properly optimized.

PMID- 23546303
TI  - Risk of topical anesthetic-induced methemoglobinemia: a 10-year retrospective
      case-control study.
AB  - IMPORTANCE: Methemoglobinemia is a rare but serious disorder, defined as an
      increase in oxidized hemoglobin resulting in a reduction of oxygen-carrying
      capacity. Although methemoglobinemia is a known complication of topical
      anesthetic use, few data exist on the incidence of and risk factors for this
      potentially life-threatening disorder. OBJECTIVE: To examine the incidence of and
      risk factors for procedure-related methemoglobinemia to identify patient
      populations at high risk for this complication. DESIGN AND SETTING: Retrospective
      study in an academic research setting. PARTICIPANTS: Medical records for all
      patients diagnosed as having methemoglobinemia during a 10-year period were
      reviewed. EXPOSURES: All cases of methemoglobinemia that occurred after the
      following procedures were included in the analysis: bronchoscopy, nasogastric
      tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and
      endoscopic retrograde cholangiopancreatography. MAIN OUTCOMES AND MEASURES:
      Comorbidities, demographics, concurrent laboratory values, and specific topical
      anesthetic used were recorded for all cases. Each case was compared with matched
      inpatient and outpatient cases. RESULTS: In total, 33 cases of methemoglobinemia
      were identified during the 10-year period among 94,694 total procedures. The mean
      (SD) methemoglobin concentration was 32.0% (12.4%). The methemoglobinemia
      prevalence rates were 0.160% for bronchoscopy, 0.005% for
      esophagogastroduodenoscopy, 0.250% for transesophageal echocardiogram, and 0.030%
      for endoscopic retrograde cholangiopancreatography. Hospitalization at the time
      of the procedure was a major risk factor for the development of methemoglobinemia
      (0.14 cases per 10,000 outpatient procedures vs 13.7 cases per 10,000 inpatient
      procedures, P < .001). CONCLUSIONS AND RELEVANCE: The overall prevalence of
      methemoglobinemia is low at 0.035%; however, an increased risk was seen in
      hospitalized patients and with benzocaine-based anesthetics. Given the potential
      severity of methemoglobinemia, the risks and benefits of the use of topical
      anesthetics should be carefully considered in inpatient populations.

PMID- 23546304
TI  - Spongiform encephalopathy in siblings with no evidence of protease-resistant
      prion protein or a mutation in the prion protein gene.
AB  - We discuss relevant aspects in two siblings with a neurodegenerative process of
      unclear aetiology who developed progressive dementia with global aphasia and
      hyperoral behaviour at the ages of 39 and 46 years and who died 6 and 5 years
      after disease onset. The cases were reported to the National Reference Center for
      TSE Surveillance in Gottingen, Germany. Detailed clinical examinations, CSF,
      blood samples, and copies of the important diagnostic tests (magnetic resonance
      imaging, electroencephalogram, laboratory tests) were obtained. Further
      neuropathological and genetic analyses were performed. Cerebral magnetic
      resonance imaging of both siblings showed prominent changes in signal intensity,
      especially in the left medial temporal cortex, but also the hippocampal
      formation. Neuropathological examination revealed spongiform changes, neuronal
      loss, and astrocytic gliosis, which are typical in Creutzfeldt-Jakob disease.
      However, no prion protein deposits were detectable by immunohistochemical
      analysis, Western blot, or PET blot, though abundant tau protein deposits were
      observed. A mutation in the coding region of the prion protein genes of both
      siblings was excluded. A detailed search of the literature revealed no other
      cases with a similar clinical and neuropathological appearance. While the disease
      aetiology remains unclear, the findings point to a neurodegenerative process and
      most likely a genetic disease.

PMID- 23546305
TI  - High-dose praziquantel therapy for cerebral sparganosis.

PMID- 23546306
TI  - Expression of 11beta-HSD in steroid-induced avascular necrosis of the femoral
      head.
AB  - The aim of the present study was to investigate the association between
      glucocorticoid receptors and steroid-induced avascular necrosis of the femoral
      head (SANFH). Healthy New Zealand rabbits were randomly divided into 3 groups
      (n=16/group); the normal (no treatment), control (horse serum injections) and
      treatment (horse serum and methylprednisolone injections) groups.
      Methylprednisolone and horse serum injections were used to establish a SANFH
      model in rabbits; magnetic resonance imaging (MRI) and histopathological analysis
      were used to evaluate the SANFH rabbit model. Total cholesterol and triglyceride
      contents in the blood of SANFH rabbits were determined. The protein expression
      levels of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and type 2
      (11beta-HSD2) were determined using western blotting. The total cholesterol and
      triglyceride levels in the blood of methylprednisolone-treated rabbits were
      significantly increased compared with the control and normal groups, which
      provides evidence in support of the metabolic disorder theory. Based on the
      results obtained from western blotting, the expression levels of 11beta-HSD1
      protein were increased, whereas the expression levels of 11beta-HSD2 protein were
      decreased following injection. The results of the present study indicate that
      11beta-HSDs are important in the development of SANFH. Furthermore, 11beta-HSDs
      may be important targets for preventing the development of ANFH in patients
      treated with steroids, which has a significant reference value for the use of
      steroids in clinical practice.

PMID- 23546307
TI  - Multidisciplinary care for stroke patients living in the community: a systematic
      review.
AB  - OBJECTIVE: A systematic review of randomized controlled trials was performed to
      evaluate the effectiveness of multidisciplinary care for stroke patients living
      in the community. DATA SOURCES: Databases PubMed, EMBASE, CINAHL and the Cochrane
      Library from January 1980 until July 2012. STUDY SELECTION: Randomized controlled
      trials focused on multidisciplinary interventions for stroke patients living at
      home after hospitalization or inpatient rehabilitation were selected. The outcome
      domains were activities of daily living, social participation and quality of
      life. A total of 14 studies were included. DATA EXTRACTION: Two authors
      independently extracted the data and independently assessed the quality of
      reporting of the included studies using the Consolidated Standards of Reporting
      Trials (CONSORT) statement 2010. DATA SYNTHESIS: None of the studies showed
      favourable effects of the intervention on activities of daily living and none
      assessed social participation. Furthermore, two studies reported favourable
      effects of the intervention in terms of quality of life. These concerned an
      intervention combining assessment with follow-up care and a rehabilitation
      intervention. CONCLUSION: There is little evidence for the effectiveness of
      multidisciplinary care for stroke patients being discharged home. Additional
      research should provide more insight into potentially effective multidisciplinary
      care for community-living stroke patients.

PMID- 23546308
TI  - Evaluating the feasibility of Goal Attainment Scaling as a rehabilitation outcome
      measure for veterans.
AB  - OBJECTIVE: The increasing number of veterans with complex health conditions
      accessing rehabilitation leads to the need for an outcome measure that identifies
      success in areas beyond return to work. The current study was designed to assess
      the feasibility of goal attainment scaling as a routine measure of outcomes of
      rehabilitation. METHODS: Fifteen organisations contracted by the Australian
      Department of Veterans' Affairs to work with veterans were invited to trial goal
      attainment scaling. Training was provided to rehabilitation professionals, and
      existing documentation was modified by the Australian Department of Veterans
      Affairs to introduce the goal attainment scaling approach. RESULTS: Analysis of
      the use of goal attainment scaling supported the feasibility and potential
      usefulness of the tool in a veteran population. Rehabilitation providers set
      goals across a range of domains including medical, psychological, social, as well
      as return to work. The quality of the goals and the outcome measures was
      generally good. CONCLUSIONS: The goal attainment scaling approach was seen to
      support a client-focussed approach to rehabilitation. Data obtained through the
      use of goal attainment scaling can be summarised at different levels to be useful
      for clients, providers, rehabilitation coordinators, and senior executives to
      monitor and report on the overall success of the different types of
      rehabilitation provided to veteran clients.

PMID- 23546309
TI  - Epstein-Barr virus latent membrane protein 1 induces CD69 expression through
      activation of nuclear factor-kappaB.
AB  - Latent membrane protein-1 (LMP-1) of Epstein-Barr virus (EBV) promotes
      tumorigenesis. Here, we report that LMP-1 activates the immunoregulatory molecule
      CD69 gene transcription through a nuclear factor-kappaB (NF-kappaB)-dependent
      pathway. CD69 expression was upregulated in LMP-1-expressing EBV-immortalized
      human B-cell lines and an EBV-positive Burkitt's lymphoma cell line. LMP-1
      expression increased CD69 expression at the transcriptional level. CD69 promoter
      was regulated by LMP-1 activation of NF-kappaB via the carboxy-terminal
      activation region 1 and 2. Promoter deletion analysis indicated that two NF
      kappaB binding sites are necessary for activation of the CD69 promoter.
      Electrophoretic mobility shift analysis demonstrated that LMP-1 activates both NF
      kappaB binding sites in the CD69 promoter. This is the first report of the
      regulation of CD69 expression by LMP-1, and this novel finding may, thus,
      represent an important link between the EBV oncoprotein LMP-1 and its critical
      role in the development of EBV-associated diseases.

PMID- 23546310
TI  - Nursing knowledge construction and occupational health.

PMID- 23546311
TI  - Moral distress in everyday nursing: hidden traces of power and resistance.
AB  - OBJECTIVE: To know the strategies of resistance adopted by nursing staff, facing
      situations of moral distress, from an ethical perspective. METHOD: The authors
      conducted qualitative research through semi-structured interviews, with fifteen
      nursing staff members of a university hospital in the extreme south of Brazil,
      using textual discourse analysis and the theoretical reference of Foucault.
      RESULTS: Two categories were constructed: denial of oneself and the other - in
      which one perceives that the nursing staff can perform actions that are governed
      predominantly by immobility and conformism, avoiding confrontations with whoever
      represents power in situations that provoke moral distress in them; possibility
      to care for oneself and for the other - in which nursing workers in situations
      that provoke moral distress for them exercise power and endurance. CONCLUSION: it
      was perceived that some professionals seem to use ethical coping strategies, in
      order to ensure and preserve their professional values. However, often the choice
      of some nursing professionals may be to relapse into immobility and the absence
      of building strategies of endurance. This situation may represent their reduced
      exercise of power and insufficient resistance in the face of ethical problems,
      contributing to the intensification of their invisibility in the area of health.

PMID- 23546313
TI  - Analysis of occupational accidents with biological material among professionals
      in pre-hospital services.
AB  - OBJECTIVE: To estimate the prevalence of accidents due to biological material
      exposure, the characteristics and post-accident conduct among professionals of
      pre-hospital services of the four municipalities of Minas Gerais, Brazil. METHOD:
      A cross-sectional study, using a structured questionnaire that was developed to
      enable the calculation of prevalence, descriptive analysis and analytical
      analysis using logistic regression. The study included 228 professionals; the
      prevalence of accidents due to biological material exposure was 29.4%, with 49.2%
      percutaneous, 10.4% mucousal, 6.0% non-intact skin, and 34.4% intact skin.
      RESULTS: Among the professionals injured, those that stood out were nursing
      technicians (41.9%) and drivers (28.3%). CONCLUSION: Notification of the
      occurrence of the accident occurred in 29.8% of the cases. Percutaneous exposure
      was associated with time of work in the organization (OR=2.51, 95% CI: 1.18 to
      5.35, p<0.017). Notification about accidents with biological material should be
      encouraged, along with professional evaluation/monitoring.

PMID- 23546312
TI  - Intervention strategies for the health of university hospital nursing staff in
      Brazil.
AB  - OBJECTIVE: The aim of this study was to propose intervention strategies for the
      health of hospital-based nursing staff. METHOD: It was a field study, with a
      quantitative and qualitative approach, developed from data collected through the
      Monitoring System of Nursing Workers' Health in seven public and university
      hospitals of Brazil. Intervention strategies proposed considered regional
      specificities and the demands presented by professionals in each setting.
      RESULTS: The interventions were developed for: each workload to which nursing
      staff was exposed; processes of strain generated; and intervention strategies at
      the settings, according to the needs of the national scenario. CONCLUSION:
      Monitoring the health of nursing staff is a beginning point for building
      strategies directed at the health profile of each reality.

PMID- 23546314
TI  - Is vaccination against hepatitis B a reality among primary health care workers?
AB  - OBJECTIVE: To verify the prevalence and factors associated with vaccination
      against hepatitis B among Primary Health Care workers in Montes Claros/MG.
      METHOD: A cross-sectional, analytic study was undertaken. Data were collected
      through a form, which contained sociodemographic, occupational, general health
      and behavioral variables. Associations were investigated through bivariate
      analysis and Poisson's multivariate regression, using SPSS 17.0. RESULTS: 95.5%
      answered the question about vaccination; 47.5% did not complete the vaccination
      scheme. The prevalence of vaccinated professionals was lower among older workers,
      who were hired, did not participate in occupational health updates and consumed
      alcohol. Prevalence levels were higher among professionals with more years of
      education and who reported contact with piercing and cutting instruments .
      CONCLUSIONS: Professional education, knowledge and perception of infection risks
      are important determinants of the vaccination scheme. Instability at work may
      lead to negligence and negligent behaviors may repeat themselves. The
      characterization of professionals who did not get vaccinated will direct
      educative actions in occupational health.

PMID- 23546315
TI  - Presence of depressive symptoms in patients with a first episode of acute
      coronary syndrome.
AB  - AIM: to compare possible differences regarding the presence of depressive
      symptoms according to the clinical diagnosis of Acute Coronary Syndrome, gender
      and age, one week before the first cardiac event. METHOD: cross-sectional,
      descriptive and exploratory study, which used the Beck Depression Inventory. The
      sample consisted of 253 patients. RESULTS: it was found that patients with a
      clinical diagnosis of unstable angina, female and under 60 years of age reported
      the presence of depressive symptoms more frequently. CONCLUSION: a high
      percentage of patients presented depressive symptoms at the time of
      hospitalization for the first episode of Acute Coronary Syndrome, and this
      prevalence was significantly higher among women, under 60 years of age, with
      unstable angina. These results should provide support for the care in the
      hospitalization, discharge and planning of the rehabilitation of these patients,
      as it is known that depression impairs the control of coronary disease.

PMID- 23546316
TI  - Understanding the process of living as signified by myocardial revascularization
      surgery patients.
AB  - OBJECTIVE: To understand the meanings for the process of living, for patients
      undergoing myocardial revascularization surgery, and to construct an explanatory
      theoretical model. METHOD: Grounded Theory was used, with data collection
      undertaken between October 2010 and May 2012, in a health institution which
      specializes in cardiac surgery, located in the south of Brazil. Thirty-three
      subjects were interviewed (patients, health care professionals and family
      members), distributed in four sample groups. RESULT: The explanatory theoretical
      model was comprised of 11 categories and the central phenomenon. The specialized
      service and the cardiac rehabilitation program formed the context, the discovery
      of the cardiac disease and the feelings experienced during the perioperative
      period were the cause and intervening conditions in the process of experiencing
      the myocardial revascularization surgery. The strategies were relying on the
      family's support, having faith and hope, and participating in the rehabilitation
      program. This process's main consequences were the confrontation of the changes
      and the resulting limitations, difficulties and adaptations to the new lifestyle
      after surgery. CONCLUSION: The process of experiencing the myocardial
      revascularization surgery constitutes an opportunity for maintaining the
      patient's life associated with the needs for confronting the significant changes
      in lifestyle.

PMID- 23546317
TI  - Care needs and workload required by institutionalised psychiatric patients.
AB  - OBJECTIVES: This descriptive study used a quantitative approach to assess the
      nursing care needs of patients with mental disorders, the mean number of care
      hours these patients were provided and the workload these patients require
      nursing team. METHODS: The research was conducted in a public neuropsychiatric
      hospital located in south eastern Brazil in 2010 and included 105 patients as
      subjects. A patient classification tool was applied to characterise care
      profiles. Statistical analysis was performed using principal component analysis
      and analysis of variance. RESULTS: Patients were predominantly in the low care
      category (73.3%). The mean care hours ranged from 0.57 to 0.88 for nurses and
      1.97 to 3.16 for nursing assistants, and the workload ranged from 119.6 to 183
      hours . CONCLUSIONS: The present study showed that the care needs of most
      patients were at a low level of dependency and that most patients did not need to
      be institutionalised. Furthermore, it was found that the care hours provided by
      the nursing staff were not sufficient to meet the care needs of the patients.

PMID- 23546318
TI  - Assessment of a neonatal unit nursing staff: application of the Nursing
      Activities Score.
AB  - OBJECTIVE: The study proposes to analyze the nursing staff workload of the
      sectors of a neonatal unit by means of the Nursing Activities Score - NAS and to
      calculate the quantitative ideal for the team, comparing it with the current
      workload. METHOD: The NAS tool was applied for all newborns interned for at least
      24 hours; the sum of the NAS points provided the unit workload which was used for
      calculating the team assessment by means of mathematical equation. RESULTS: The
      sector of Low Risk presented a workload of 267 NAS points and an imbalance of 8.8
      professionals daily; the Medium Risk sector a workload of 446.7 and an imbalance
      of 22.3; the High Risk sector a workload of 359 and a deficit of 17.9; the
      Isolation sector a demand of 609 and an imbalance of 18.2; and NICU a workload of
      568.6 with a deficit of 16.1 professionals. CONCLUSION: The study disclosed an
      important imbalance of professionals in relation to the exalted work demand they
      are subjected to daily. The application of the Nursing Activities Score in
      neonatal units contributes to the evaluation of the workload and assessment of
      the nursing team.

PMID- 23546319
TI  - Stress related to care: the impact of childhood cancer on the lives of parents.
AB  - OBJECTIVES: The objective was to assess the stress levels of parents of children
      with cancer and to identify correlations among demographic data and anxiety
      levels. METHODS: A descriptive, cross-sectional study, conducted in two Brazilian
      institutions, with 101 parents of children with cancer. Through interviews,
      parents responded to two instruments: Pediatric Inventory for Parents - Brazilian
      version, which assesses stress levels, and State-Trait Anxiety Inventory, for the
      measurement of anxiety. The correlations between the instruments and the
      sociodemographic variables of the parents and children were evaluated using the
      Spearman correlation coefficient. RESULTS: Higher levels of stress and anxiety
      were seen by young parents, young children and with less time since diagnosis.
      The fear of death and the disease impact on the life of a child were the events
      considered the most stressful for the parents . CONCLUSIONS: In clinical
      practice, the nurse who can identify the occurrence of these symptoms becomes
      capable of planning nursing care that includes the family in decisions about the
      care. Moreover, she can provide support to help parents manage their stress
      levels and positively face the illness of their children.

PMID- 23546320
TI  - Evaluation of an educational technology regarding clinical evaluation of preterm
      newborns.
AB  - AIM: To evaluate, from the students' point of view, educational software
      developed as a tool to help teachers and students in neonatal nursing. METHOD:
      The study evaluates the contents and simulations addressed in the software. A
      total of 57 undergraduate nursing students affiliated with five Brazilian public
      colleges participated. RESULTS: The general assessment of the software was highly
      satisfactory: 82.4% of the sample characterized the software as quite effective
      as a teaching tool. Most components were assessed as good or very good. The
      participants' suggestions and comments are being considered in the improvement
      and adaptation of the new software version. CONCLUSION: The results show that the
      product is adequate for use in neonatal nursing courses and nursing training on
      the physical examination techniques and semiology of preterm newborns, falling
      within the pedagogical framework of active methods.

PMID- 23546321
TI  - Apparent and content validation of maternal self-efficiency scale for prevention
      of childhood diarrhea.
AB  - AIM: The aim of this paper is to describe the apparent and content validation for
      the Maternal Self-Efficiency Scale for the Prevention of Childhood Diarrhoea.
      METHOD: Methodological study with the execution of apparent and content
      validation by seven judges; semantic analysis, by 30 mothers of children under 5
      years old and also a pre-test involving 31 mothers who have been selected through
      convenience. It has been considered necessary to have the agreement of at least
      70% of the judges for apparent validation and a minimum of 80% for pertinence and
      Index of Content Validation. RESULTS: This paper shows that most items have been
      considered clear, comprehensive and relevant by the judges. The final Content
      Validity Index of the scale was 0.96. The suggestions of the mothers were
      accepted. CONCLUSION: The scale ended up having 25 items and two domains (family
      hygiene and general/eating practices) which assess the maternal self-efficiency
      for the prevention of diarrhea in their children, thereby contributing to the
      planning of nursing interventions.

PMID- 23546322
TI  - The process of end-of-life care delivery to the families of elderly patients
      according to the Family Health Strategy.
AB  - OBJECTIVE: To understand the process of end-of-life care delivery to the families
      of elderly patients according to a Family Health Strategy (FHS) team, to identify
      the meanings the team attributes to the experience and to build a theoretical
      model. METHOD: Symbolic Interactionism and Grounded Theory were applied. Fourteen
      professionals working in an FHS located in a country town in the state of Sao
      Paulo were interviewed. RESULTS: Through comparative analysis, the core category
      overcoming challenges to assist the family and the elderly during the dying
      process was identified, and it was composed of the following sub-processes:
      Identifying situational problems, Planning a new care strategy, Managing the care
      and Evaluating the care process. CONCLUSION: the team faces difficulties to
      achieve better performance in attending to the biological and emotional needs of
      families, seeking to ensure dignity to the elderly at the end of their lives and
      expand access to healthcare.

PMID- 23546323
TI  - Transcultural adaptation and validation of the Stanford Presenteeism Scale for
      the evaluation of presenteeism for Brazilian Portuguese.
AB  - OBJECTIVE: describe the process of transcultural adaptation and validation of the
      Stanford Presenteeism Scale for Brazilian Portuguese. METHODS: Methodological
      study of the cultural adaptation and validation of the tool which involved 153
      nursing staff and included six aspects of equivalence, obtained through the
      following stages: translation, first version of consent, retranslation,
      specialist committee, pre-test, study of test-retest credibleness and dimensional
      validity. RESULTS: The stability of the items varied from moderate to almost
      perfect and the sequence constancy was almost perfect. Two factors were
      identified through the exploratory fact analysis: the first one included the
      physical aspects - completing work; and the second one the psychological aspects 
      avoided distraction . CONCLUSIONS: the results suggest adequacy of the tool in
      the Brazilian Portuguese version, indicating its use in the context of the study
      group and in similar groups, contributing to the study of evidences which
      consolidate strategies that favor the health conditions of the jobholders.

PMID- 23546324
TI  - Psychometric analysis of the scale for the predisposition to the occurrence of
      adverse events in nursing care provided in ICUs.
AB  - OBJECTIVE: to present the result of the validity and reliability studies
      concerning the Scale for the Predisposition to the Occurrence of Adverse Events
      (EPEA). METHOD: construct validity was based on Principal Components Analysis.
      RESULTS: reliability verified through Cronbach's alpha indicated good reliability
      (structure alpha=0.80; process alpha=0.92). CONCLUSION: based on its psychometric
      indicators, the EPEA can be considered a valid measure to assess the attitudes of
      nurses in relation to factors that potentially lead to the occurrence of adverse
      events in ICUs.

PMID- 23546325
TI  - Adaptation and validation of the instrument positions on the nursing process.
AB  - OBJECTIVE: estimate the psychometric properties in the adaptation of the
      instrument Positions on Nursing Diagnosis to assess nursing staff members'
      attitudes towards the nursing process. METHOD: methodological study with a non
      probabilistic sample of 973 nursing assistants and 632 baccalaureate nurses from
      35 hospitals and outpatient clinics affiliated with the Sao Paulo State Health
      Secretary. The validity of the 20-items instrument was checked through
      confirmatory factor analysis, which identified a more generally secondary-level
      factor, constituted by the three classical attitude factors. Reliability
      corresponded to 0.954 for the total instrument. RESULTS: the validity and
      reliability of the instrument Posicoes sobre o Processo de Enfermagem are
      appropriate . CONCLUSIONS: further research is needed to verify whether the items
      behave differently according to the respondent's professional category and to
      verify the instrument's behavior when applied to student samples.

PMID- 23546326
TI  - The image of care delivery by public health nurses as disseminated in Revista da
      Semana (1929).
AB  - OBJECTIVE: to analyze the images of Public Health Nurses in care delivery to
      society, disseminated by the Revista da Semana, in 1929. METHOD: historical
      semiotic study. The documents used were images, to which an analysis matrix was
      applied, including fashion and body language literature, besides others to
      address the study object. The data were interpreted in the light of the
      sociologist Pierre Bourdieu's notions of object representations and body hexis.
      RESULTS: the distinctive use of uniforms for the Public Health Nurses' activities
      was a non-verbal communication strategy to gain visibility and credibility during
      home visits . CONCLUSIONS: Public Health Nurses were particularly responsible for
      patient care and guidance to prevent illnesses, with a view to the qualitative
      development of Public Health. The intent in this study was to produce knowledge
      on image records about nurses' care practice at the National Public Health
      Department's School of Nurses, as well as to strengthen Public Health Nursing
      History research in Brazil, thus contributing to a better understanding about the
      construction process of nurses' image.

PMID- 23546327
TI  - Educational intervention for liver transplantation candidates.
AB  - OBJECTIVE: The objective in this study was to analyze candidates' knowledge on
      the liver transplantation process before and after putting in practice an
      educational intervention. METHOD: A quasi-experimental, one-group pretest
      posttest research design was adopted. The final sample included 15 subjects.
      Research data were collected between January and March 2010 in three phases,
      which were: pretest, implementation of the educational intervention (two
      meetings) and posttest. RESULTS: The results evidenced significant cognitive
      gains after the intervention, with improvements in the participants' performance
      . CONCLUSIONS: The research presents evidence that putting in practice a patient
      education strategy can enhance candidates' knowledge on the liver transplantation
      process and consequently contribute to a successful treatment.

PMID- 23546329
TI  - Prevalence and factors associated with alcohol use among pregnant adolescents.
AB  - AIM: to identify alcohol use and the associated factors in pregnant adolescents
      of the municipality of Teresina-PI. METHOD: this is cross-sectional study with
      256 pregnant adolescents whose data were obtained through questionnaires covering
      socioeconomic, pregnancy and alcohol consumption characteristics and through the
      application of the Alcohol Use Disorders Identification Test, an instrument
      developed by the World Health Organization for screening for the excessive use of
      alcohol. Descriptive statistical analysis was performed using the chi-square test
      and odds ratio. RESULTS: the study indicates a prevalence of 32.4% for alcohol
      use during pregnancy in adolescents. Of these, 36.1% had scores consistent with
      risky use. The factors associated with an increased risk of alcohol use during
      pregnancy are: not having a partner, living on less than 1 minimum wage, not
      being religious, performing up to 3 prenatal consultations, having suffered
      violence and alcohol use in previous pregnancies. CONCLUSION: a high prevalence
      of alcohol consumption by pregnant adolescents and various risk factors involved
      in this process were identified. These data reflect the need for the use, by
      nurses, of screening technologies for alcohol consumption during pregnancy and
      health promotion strategies among groups of adolescents.

PMID- 23546328
TI  - The importance of protecting surgical instrument tables from intraoperative
      contamination in clean surgeries.
AB  - OBJECTIVE: to compare the degree of bacterial contamination of surgical
      instrument tables used in clean surgical procedures, either protected with
      plastic fields, sterilized with ethylene oxide, or disinfected with 70% alcohol
      and 1% iodine solutions. This is a randomized clinical trial in which samples
      were collected from the surfaces of surgical instrument tables before and after
      each procedure. Microbiological analysis was performed to identify microorganisms
      and their respective antimicrobial resistance. RESULTS: Bacterial growth in the
      surgeries using sterilized plastic was 5.71% before and 28.6% after surgery and,
      2.9% and 45.7% respectively in surgeries using disinfection with 70% alcohol and
      1% iodine solutions; no statistical difference was found between the methods.
      CONCLUSION: both methods present similar protection, however, 70% alcohol and 1%
      iodine do not generate solid waste.

PMID- 23546330
TI  - Using an experimental model for the study of therapeutic touch.
AB  - OBJECTIVE: to verify whether the Paw Edema Model can be used in investigations
      about the effects of Therapeutic Touch on inflammation by measuring the variables
      pain, edema and neutrophil migration. METHOD: this is a pilot and experimental
      study, involving ten male mice of the same genetic strain and divided into
      experimental and control group, submitted to the chemical induction of local
      inflammation in the right back paw. The experimental group received a daily
      administration of Therapeutic Touch for 15 minutes during three days. RESULTS:
      the data showed statistically significant differences in the nociceptive
      threshold and in the paw circumference of the animals from the experimental group
      on the second day of the experiment. CONCLUSION: the experiment model involving
      animals can contribute to study the effects of Therapeutic Touch on inflammation,
      and adjustments are suggested in the treatment duration, number of sessions and
      experiment duration.

PMID- 23546331
TI  - Atypical mycobacterias associated to acupuncuture: an integrative review.
AB  - AIM: to evaluate evidence concerning sources or mechanisms of infection
      transmission of atypical mycobacteria associated with acupuncture, and the
      species causing infections. METHOD: research was performed in December 2011 in
      the databases of LILACS, MEDLINE, EMBASE, OvidSP and the Cochrane Library,
      without restrictions regarding publication date, study type or language. RESULTS:
      of the 16 publications, only one identified the contamination source: diluted
      glutaraldehyde solution used to clean equipment. Three established likely
      sources: towels, hot packs or boiling tank water, and the reuse of reprocessed
      needles. Four indicated possible sources: contaminated needles, reuse of personal
      needles, patient's skin colonized by mycobacteria and reuse of needles at
      different sites in the same patient. Eight of the studies did not mention the
      sources. CONCLUSION: among 295 cases, M. abscessus was the pathological agent in
      over 96%. Well-established control practices for infection prevention should be
      implemented and adapted for complementary and alternative medicine.

PMID- 23546332
TI  - Integrative review: evidences on the practice of intermittent/indwelling urinary
      catheterization.
AB  - OBJECTIVE: to seek the best evidence available in the literature concerning the
      knowledge produced and related to the techniques of intermittent and indwelling
      urinary catheterization, so as to place the nursing care given to patients
      submitted to urinary catheterization on a scientific foundation and to prevent
      urinary tract infections. METHOD: the literature search was undertaken in the
      Pubmed and Cochrane databases for the development of the integrative review. The
      sample was of 34 articles. These were analyzed by two independent researchers
      using an instrument adapted for ascertaining the level of evidence and the grade
      of recommendation, in addition to the use of the Jadad scale. RESULTS: the
      evidence available related to the nursing care for patients submitted to urinary
      catheterization is: the infection rate in the urinary tract does not alter
      whether the perineum is cleaned with sterile water or not, or with the use of
      povidone-iodine solution or chlorhexidine; or using clean or sterile technique.
      The use of an intermittent catheter with clean technique results in low rates of
      complications or infections compared to the use of an indwelling catheter. The
      removal of the catheter in up to 24 hours after surgery and the use of an
      antimicrobial-impregnated or hydrophilic-coated catheter reduce urinary tract
      infection . CONCLUSIONS: there are controversies in relation to periurethral
      cleansing technique, the type of material the catheter is made of, and some
      procedures for the maintenance and removal of the catheter. This review's results
      represent an updating of the nurse's conducts and decision-making for the
      prevention of urinary tract infections in urinary catheterization.

PMID- 23546333
TI  - Baicalin attenuates acute myocardial infarction of rats via mediating the mitogen
      activated protein kinase pathway.
AB  - Baicalin is a bioactive ingredient from the herb and has possessed various
      pharmacological actions. The present study was performed to evaluate the
      cardioprotective potential of baicalin against myocardial infarction and explore
      the potential mechanism. Baicalin was intraperitoneally injected into the rats by
      the doses of 50, 100 and 200 mg/kg, respectively, once a day for 7 d and, 30 min
      after the last administration, the left coronary artery was ligated. Infarct size
      was measured to analyze the myocardial damage. Myocardial specific enzymes,
      including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB),
      lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were determined with
      the colorimetric method. Evidence for myocardial apoptosis was detected by
      caspase-3 activity measurement and Western blot analysis. We also examined the
      protein levels of three major subgroups of mitogen-activated protein kinases
      (MAPKs), namely, extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK) and p38 by immuoblotting. Our results indicated that baicalin
      significantly reduced the infarct size and myocardial enzymes (CK, CK-MB, LDH and
      cTnT). Administration of baicalin also suppressed the activity and protein
      expression of caspase-3. Moreover, the protein level of phosphorylated ERK (p
      ERK) was found to be evidently augmented while the phosphorylated JNK (p-JNK) and
      phosphorylated p38 (p-p38) were strikingly diminished in infarcted rats with
      baicalin treatment. These findings suggest that the baicalin's cardioprotection
      associates with mediation of MAPK cascades in acute myocardial infarction of
      rats.

PMID- 23546334
TI  - Anodic aluminium oxide membranes for immunoisolation with sufficient oxygen
      supply for pancreatic islets.
AB  - Immunoisolation membranes have been developed for various cell encapsulations for
      therapeutic purposes. However effective encapsulation systems have been hindered
      by low oxygen (O2) permeability or imperfect immunoisolation caused by either low
      porosity or non-uniform pore geometry. Here, we report an encapsulation method
      that uses an anodic aluminum oxide membrane formed by polyethylene oxide self
      assembly to obtain nanochannels with both high selectivity in excluding immune
      molecules and high permeability of nutrients such as glucose, insulin, and O2.
      The extracorporeal encapsulation system composed of these membranes allows O2
      flux to meet the O2 demand of pancreatic islets of Langerhans and provides
      excellent in vitro viability and functionality of islets.

PMID- 23546335
TI  - Children's exposure to mercury-contaminated soils: exposure assessment and risk
      characterization.
AB  - Exposure to mercury (Hg)-contaminated soils may pose a health risk to children by
      way of oral, dermal, and inhalatory pathways. However, risk characterization
      studies, including contaminant bioaccessibility with child-specific exposure
      parameters and scenarios, are lacking. The objectives of this study were (1) to
      assess children's Hg exposure using characterization and oral bioaccessibility
      data from Hg-contaminated soils characterized in previous studies (n = 8); and
      (2) to characterize probabilistic risk in terms of hazard index (HI) considering
      ingestion, dermal, and inhalation pathways. Total Hg concentrations in soils
      ranged from 2.61 to 1.15 * 10(4) mg kg(-1). For moderately contaminated soils (S1
      S5: Hg <= 12.15 mg kg(-1)), low oral bioaccessibility values (1.5-7.5 %) lead to
      HI < 1 in all scenarios. However, exposure to highly contaminated soils (S6-S8)
      may pose serious risks to children under normal exposure (HI 0.89-66.5) and soil
      pica behaviour scenarios (HI up to 131). All three pathways significantly
      contributed to the risk. Using total Hg concentrations in calculations (assuming
      100 % bioavailability) instead of considering Hg bioavailability leads to risk
      overestimation. Further research on oral, inhalatory, and dermal bioavailability
      of Hg, as well as child play behaviour, is recommended to obtain more accurate
      risk estimates.

PMID- 23546336
TI  - Are symptoms of restless legs syndrome generated in the periphery of the nervous
      system or are they born centrally?

PMID- 23546337
TI  - The current role of endoscopes in intracranial tumor surgery.

PMID- 23546338
TI  - Recurrent intraventricular cysticercal cyst.

PMID- 23546339
TI  - On the trail of cerebral sinus venous events in inflammatory bowel diseases.

PMID- 23546340
TI  - Effect of hyperglycemia on conduction parameters of tibial nerve's fibers to
      different muscles: A rat model.
AB  - INTRODUCTION: Routine conduction studies reflect the summation of all nerve
      fibers in a peripheral nerve. Nerve fiber groups to distal, small muscles have
      smaller diameters than the ones to large proximal muscles. There may be minimal
      differences between the diameters of nerve fiber groups innervating different
      muscles; even they are all same type of fibers. So, in neuropathic processes some
      nerve fiber groups may be more seriously affected. MATERIALS AND METHODS: 14 rats
      ( 7 diabetic, 7 control) were studied. Tibial nerve was stimulated from two
      points and while recorded from a distal (foot intrinsic muscles) and a proximal
      (gastrocnemius) muscle. RESULTS: There was a significant difference between the
      proximal and distal recorded conduction velocities. Both proximal and distal
      recorded conduction velocities decreased during the hyperglycemic process.
      DISCUSSION: Our method successfully demonstrated different nerve fiber groups;
      but, the neuropathic process seemed to be homogeneous in both fiber groups.

PMID- 23546341
TI  - Injection nerve palsy.
AB  - OBJECTIVE: To study the clinical profile and outcome of surgery for injection
      nerve palsies. MATERIALS AND METHODS: This is a retrospective study of patients
      with INP who were treated at our institute during May 2000 to May 2009. Clinical,
      electroneuromyography (ENMG), and operative findings were noted. Intraoperative
      nerve action potential monitoring was not used in any case. Outcome of patients
      who were followed was reviewed. RESULTS: INP comprised 92 (11%) of 837 nerve
      injury patients. Seventy one patients were children less than 16 years. The
      nerves involved were sciatic in 80 patients, radial in 8, and others in four.
      Fifty seven patients had power, grade 0/5. ENMG studies revealed absent compound
      muscle action potential in 64 and absent sensory nerve action potential in 67
      patients. Thirty nine (42.3%) of 92 patients underwent surgery. The mean duration
      since injury in these patients was 5.2 months (3 months to 11 months). All
      underwent neurolysis. Only 18 patients who underwent surgery had a follow up of
      more than 3 months. Ten (55.5%) patients had good or fair outcome after surgery.
      Except for grade of motor deficit prior to surgery, none of the variables were
      found to significantly affect the outcome. CONCLUSION: The outcome of INP is
      generally good and many patients recover spontaneously. The outcome of surgery is
      dependent on preoperative motor power.

PMID- 23546342
TI  - Domestic animal-related neuro-trauma: An account, from a tertiary institute.
AB  - CONTEXT: Experience of animal-related neurotrauma at an apex institute, National
      Institute of Mental Health and Neurosciences, Bangalore, India. AIMS: The aim of
      this study is to review epidemiology, clinical findings, and outcome of animal
      related traumatic brain injury (TBI) evaluated and treated at our institute.
      SETTINGS AND DESIGN: A retrospective study consisting of demographic data,
      clinical findings, radiological details, and outcomes. MATERIALS AND METHODS: The
      clinical and imaging records of 30 patients treated for animal-related TBI at the
      emergency services, from January to July 2010. Outcome was assessed by Glasgow
      outcome scale (GOS). STATISTICAL ANALYSIS USED: SPSS 15.0 version, descriptive
      statistics. RESULTS: A total of 6190 neurotrauma cases were evaluated and treated
      during the study period. Among them, 30 (0.48%) were animal-inflicted injuries.
      Of these cases, animal-vehicle collision and directly animal-inflicted injuries
      were 15 (50%) each. The mean age of patients were 39.46 (6-71 years). Twenty-nine
      (96.66%) cases were from rural areas. Twenty-three (76.6%) had mild, 6 (20%) had
      moderate, and 1 (3.3%) had severe head injury (Glasgow coma scale). Four (13.3%)
      patients had abnormal pupillary reaction. Associated injuries were found in 25
      (83.3%) patients. CT scan was abnormal in 50% (15/30), common finding was
      contusion in 8 (26.6%) patients, followed by edema in 6 (20%). There were 3 (10%)
      spine injuries, 1 (3.3%) internal carotid artery (ICA) dissection, and 2 (6.6%)
      brachial plexuses injuries. Three (10%) required surgery, and 1 (3.3%) patient
      expired. As per the GOS, good recovery was seen in 8 (80%) patients, moderate
      disability in 1 (10%), and vegetative state in 1 (10%) patient.

PMID- 23546343
TI  - Hyponatremia after aneurysmal subarachnoid hemorrhage: Implications and outcomes.
AB  - BACKGROUND: Hyponatremia is the most common electrolyte abnormality seen in
      patients with aneurysmal SAH. Clinically significant hyponatremia (Serum Sodium
      <131 mEq/L) which needs treatment, has been redefined recently and there is a
      paucity of outcome studies based on this. This study aims to identify the mean
      Serum Sodium (S.Na+) level and its duration among inpatients with SAH and to
      identify the relationship between hyponatremia and the outcome status of patients
      undergoing surgery for SAH. MATERIALS AND METHODS: This outcome study is
      undertaken in the department of neurosurgery, The Sree Chitra Tirunal Institute
      for Medical Sciences and Technology, Trivandrum, Kerala. Medical records of all
      patients with SAH from 1(st) January to 31(st) July 2010 were reviewed.
      Preoperative status was assessed using World Federation of Neurosurgical
      Societies (WFNS) grading system. Discharge status was calculated using the
      Glasgow outcome score scale. RESULTS: Fifty nine patients were included in the
      study and 53 (89.8%) of them have undergone surgical treatment. Hyponatremia was
      observed in 22 of 59 patients (37%). The mean Sodium level of hyponatremic
      patients was 126.97 mEq/L for a median duration of two days. Glasgow outcome
      score was good in 89.8% of patients. We lost two patients, one of whom had
      hyponatremia and vasospasm. CONCLUSION: Hyponatremia is significantly associated
      with poor outcome in patients with SAH. Anticipate hyponatremia in patients with
      aneurysmal subarachnoid hemorrhage, timely detect and appropriately treat it to
      improve outcome. It is more common in patients who are more than 50 years old and
      whose aneurysm is in the anterior communicating artery. Our comprehensive
      monitoring ensured early detection and efficient surgical and nursing management
      reduced morbidity and mortality.

PMID- 23546344
TI  - Elderly pedestrian neurotrauma: A descriptive study from a premier neurotrauma
      center in India.
AB  - CONTEXT: Experience with elderly pedestrian neurotrauma at a major neurotrauma
      tertiary center. AIMS: To highlight the specific injuries and outcome of the
      elderly pedestrian neurotrauma patients within the city of Bangalore and its
      surrounding districts. SETTINGS AND DESIGN: A retrospective study consisting of
      demographic data, clinical findings, radiological details, and outcomes.
      MATERIALS AND METHODS: A study was conducted at the casualty services, in which
      143 consecutive elderly pedestrian (age >60 years) head injury victims were
      studied from June to September 2009. The records from the hospital mortuary were
      analyzed from 2007 to 2009. An analysis of 77 elderly patients who died as a
      pedestrian in accidents during this period was performed. STATISTICAL ANALYSIS
      USED: SPSS 15. RESULTS: The elderly pedestrians constituted 27% (143/529) of all
      pedestrian traumas. Two wheelers were the most common accident vehicle (56.6%,
      81/143). Most of the injuries (38.5%, 55/143) occurred during peak traffic hours,
      that is, 4 pm to 9 pm. Majority sustained moderate to severe head injury (61%,
      87/143). More than three-fourths of patients required a computed tomography (CT)
      scan (77%, 110/143), in which there was a higher frequency of contusion (31.5%,
      45/143), and subdural hemorrhage (23.1%, 33/143). Most of the injured (43.3%,
      13/30) underwent surgery for intracranial hematoma. The mortality rate was 22.8%
      (8/35). Nearly one-fourth of conducted postmortems among pedestrians belonged to
      the elderly age group (77/326, 23.6%). CONCLUSIONS: Elderly pedestrian
      neurotrauma patients sustain a more severe injury as evident by poorer Glasgow
      Coma Score (GCS) scores and CT scan findings, and hence have a higher mortality
      rate.

PMID- 23546345
TI  - Initial management of traumatic brain injury in the rural setting.
AB  - Healthcare workers in the rural setting face unique problems when dealing with
      head injured patients however the basic principle of medical management are the
      same in any situation. The key initial elements remain aggressive early
      resuscitation followed by a comprehensive assessment of conscious level and
      either early consultation or transfer to a neurosurgical facility. What has
      improved considerably over recent years is the understanding of the
      pathophysiology of traumatic brain injury and as such some of the medical
      management strategies have changed. A basic understanding of some of these
      concepts is useful in the clinical setting and serves to emphasis the importance
      of effective early medical management. Thereafter consideration must be given to
      which patients require radiological investigations and possible discussion with
      or transfer to a neurosurgical facility.

PMID- 23546346
TI  - Wernicke's encephalopathy and central pontine myelinolysis in hyperemesis
      gravidarum.
AB  - A pregnant woman, who had been suffering from hyperemesis gravidarum, presented
      with alteration of consciousness, ocular nystagmus and ataxia. Magnetic Resonance
      Imaging of the brain showed typical findings of Wernicke's encephalopathy and
      central pontine myelinolysis. The clinical features responded dramatically to
      thiamine supplementation.

PMID- 23546347
TI  - Commentary.

PMID- 23546348
TI  - Commentary.

PMID- 23546349
TI  - Symptomatic bilateral isolated perforator infarction following aneurysmal
      subarachnoid hemorrhage.
AB  - Vasospasm following aneurysmal subarachnoid hemorrhage (SAH) occurs in the
      extraparenchymal vessels in the subarachnoid space at the base of the brain.
      Ischemia/ Infarction affecting primarily the perforator vessels in isolation,
      following aneurysmal SAH is uncommon. A 28-year-old man with a ruptured middle
      cerebral artery aneurysm underwent clipping of the aneurysm. He developed delayed
      bilateral deep seated infarcts involving both internal capsular regions, the
      thalamus and basal ganglia without any major vessel infarct. The patient was
      managed with triple H (hypertensive hypervolemic hemodilutional) therapy and
      calcium channel antagonists but did not show any improvement and remained in poor
      neurological status. Perforator vasospasm occurring secondary to aneurysmal SAH,
      though documented in experimental animal studies, has rarely been reported in
      humans in a clinical setting. The present case provides evidence, albeit
      indirect, of isolated perforator vasospasm, which possibly should be the target
      of future therapeutic strategies.

PMID- 23546350
TI  - Commentary.

PMID- 23546351
TI  - Commentary.

PMID- 23546352
TI  - Three cases of acute myositis in adults following influenza-like illness during
      the H1N1 pandemic.
AB  - Acute viral myositis is a rare condition that occurs during the recovery phase of
      an illness, most commonly influenza. It is characterized by muscle pain and
      weakness with an isolated laboratory finding of elevated serum creatine kinase
      (CK). We describe three previously healthy patients who were hospitalized after
      developing myositis following influenza-like illness during the 2009 influenza A
      (H1N1) virus pandemic. All experienced myalgias and weakness in all four
      extremities, including distal upper extremities, associated with an elevated CK
      level that resolved along with their myalgias and weakness within one week with
      supportive care. These cases serve as a reminder that influenza-related myositis
      may have atypical characteristics depending on the strain of influenza, and
      clinicians should be open to this possibility when new outbreaks occur.

PMID- 23546353
TI  - Limb-shaking transient ischemic attack.
AB  - Limb shaking Transient Ischemic Attack is a rare manifestation of carotid
      occlusive disease. The symptoms usually present with seizure like activity and
      often misdiagnosed as focal seizures. Only on careful history the important
      clinical clues-which may help in differentiating from seizure-are revealed: Lack
      of Jacksonian march or aura; precipitation by maneuvers that lead to carotid
      compression. We present the case of an elderly gentleman with recurrent limb
      shaking transient ischemic attacks that was initially diagnosed as a case of
      epilepsy. His symptoms responded to optimization of blood pressure. The case
      report highlights the importance of accurate diagnosis as the treatment of the
      associated carotid artery occlusion may not only abolish the attacks but also
      reduce the risk of future stroke.

PMID- 23546354
TI  - Transient electromyographic findings in serotonergic toxicity due to combination
      of essitalopram and isoniazid.
AB  - Here, we report a case of serotonergic toxicity due to combination of
      essitalopram and isoniazid, which was rarely reported before. Moreover, we
      observed transient neurogenic denervation potentials in needle electromyography,
      which disappeared with the treatment of serotonergic toxicity. As to our best
      knowledge, this is the first case, reporting transient electromyographic changes
      probably due to serotonergic toxicity.

PMID- 23546355
TI  - Role of intraoperative squash smear cytology as a diagnostic modality in lipoma
      of quadrigeminal cistern.
AB  - Quadrigeminal lipoma is a rare tumor that has been categorized as developmental
      malformation rather than a hamartoma or true neoplasm, due to its origin from
      abnormal persistence and mal-differentiation of meninx primitiva during the
      development of the subarachnoid cisterns. Reported admixture of adipose tissue
      with heterotopic elements also supports a developmental origin. Quadrigeminal
      lipomas are frequently asymptomatic and detected incidentally. Though a favorable
      clinical course is usually expected, recurrences may occur due to partial removal
      of lesions in close relation to vital structure. We describe the role of
      intraoperative squash smear cytology as a diagnostic aid in quadrigeminal cistern
      lipoma and an alternative to frozen sections that are technically difficult to
      obtain due to presence of lobules of fibro-adipose tissue. With radiological
      correlation, squash cytology can be an economical method for intraoperative
      diagnosis, pending subsequent histopathological confirmation.

PMID- 23546356
TI  - Charles bonnet syndrome, management with simple behavioral technique.
AB  - Charles Bonnet syndrome occurs in visually impaired but cognitively normal
      individuals. This report describes a condition of vivid visual hallucination
      (phantom images) in an 85-year-old conscious man, who had been blind by bilateral
      progressively worsening glaucoma. This common, but rarely reported, condition was
      managed by behavioral approach of repeated blinking, intermittent eyes closure,
      and reassurance. While emotional, mood and cognitive disorders need to be ruled
      out, the condition, though frightening to the afflicted, is benign and remediable
      with simple, inexpensive approach. Health workers managing people with terminal
      blindness should always ask for the presence of hallucinations from their
      patients to forestall a preventable distress resulting from wrong perception
      without visual stimulus.

PMID- 23546357
TI  - Commentary.

PMID- 23546358
TI  - Is neurocysticercosis a risk factor for glioblastoma multiforme or a mere
      coincidence: A case report with review of literature.
AB  - Simultaneous occurrence of Neurocysticercosis (NC) along with Glioblastoma
      Multiforme (GBM) is a very rare presentation. We herein describe a case report of
      treated case of NC 2 years back who presented with secondary GBM. The brief
      report highlights that there may be some associated factors which may lead to
      development of secondary GBM in preexisting helminthic infection.

PMID- 23546359
TI  - Generalized hyperpigmentation in Wilson's disease: An unusual association.
AB  - Wilson's disease, an autosomal recessive disorder of copper metabolism, most
      commonly presents either with hepatic or neurological features. But, it may
      sometimes have certain atypical presentations posing diagnostic difficulties. We
      report here a case of Wilson's disease presenting with generalized
      hyperpigmentation of skin who also developed neurological manifestations
      subsequently. We aim to highlight the importance of keeping Wilson's disease as
      one of the differentials in patients who present with hyperpigmentation and
      neurological symptoms compatible with copper deposits in the central nervous
      system and proceed for investigations accordingly.

PMID- 23546360
TI  - Commentary.

PMID- 23546361
TI  - Commentary.

PMID- 23546362
TI  - Phenytoin induced life threatening macroglossia in a child.
AB  - Isolated acquired macroglossia of tongue rarely reported. It occurs due to causes
      like hereditary angioedema, localized angioedema, etc., Here we describe an 8
      year-old boy developing life threatening localized angioedema of tongue due to
      phenytoin without any association with drug reaction with eosinophilia and
      systemic symptoms (DRESS) syndrome or pseudolymphoma encountered in rural medical
      college. Anticonvulsants, that is, phenytoin induced this isolated peculiar
      complication, which was not described before.

PMID- 23546363
TI  - Restlessness in right upper limb as sole presentation of restless legs syndrome.
AB  - Restless legs syndrome (RLS) rarely affects the upper limb during the initial
      course of disease. We present a patient who complained of symptoms suggesting RLS
      in the right upper limb as the sole manifestation of illness. Bilateral cervical
      ribs and depression were co-incidental findings. Patient responded well to
      dopaminergic therapy.

PMID- 23546364
TI  - Commentary.

PMID- 23546365
TI  - Commentary.

PMID- 23546366
TI  - Commentary.

PMID- 23546367
TI  - Cerebral venous thrombosis in ulcerative colitis.
AB  - Ulcerative colitis has been reported to show hyper coagulation leading to
      peripheral and rarely central thrombosis. A 35-year-old female was admitted with
      chief complaints of increased frequency of bloody diarrhea, abdominal pain, and
      weight loss for 2 months. The patient was diagnosed to have ulcerative colitis
      after sigmoidoscopy and biopsy and she was started on treatment. Two days later,
      the patient developed headache and seizures. Magnetic resonance imaging of brain
      showed cerebral venous thrombosis with venous infarcts. A high index of clinical
      suspicion is needed to diagnose this uncommon condition so that appropriate
      treatment can be initiated.

PMID- 23546368
TI  - Repeated hydrocephalus in recurrent intraventricular neurocysticercosis: An
      uncommon presentation.
AB  - A rare case of a 42-years old man presented with repeated hydrocephalus due to
      the neurocysticercosis cyst (NCC) in the lateral ventricle. Patient was operated
      previously 21/2 years back for a similar lesion at same site. Both times he was
      treated endoscopically with removal of the cyst. Interestingly there was no
      parenchymatous lesion at any stage of follow up. Isolated recurrent
      intraventricular NCC is a rare condition that has never been reported in the
      literature.

PMID- 23546369
TI  - Commentary.

PMID- 23546370
TI  - Commentary.

PMID- 23546371
TI  - Commentary.

PMID- 23546372
TI  - Commentary.

PMID- 23546373
TI  - Total intracranial shunt migration.

PMID- 23546374
TI  - Commentary.

PMID- 23546375
TI  - Jacob Mathew v. State of Punjab, the judgment stipulates the guidelines to be
      followed before launching a prosecution against a doctor for negligence.
AB  - In a landmark judgment, the supreme court of India laid down guidelines in cases
      of alleged negligence against medical practitioners in India. It clearly stated
      that there is a need for protecting doctors from frivolous or unjust prosecution.

PMID- 23546376
TI  - Anesthetic management of spinal decompression in double vessel coronary artery
      disease.

PMID- 23546377
TI  - Opalski's syndrome: A rare variant of lateral medullary syndrome.

PMID- 23546378
TI  - Bregmatic dermoid cyst in a patent anterior fontanelle.

PMID- 23546379
TI  - Delayed cerebral vasospasm following surgery for craniopharyngioma.

PMID- 23546380
TI  - Commentary.

PMID- 23546381
TI  - A comment on effect of fluoride exposure on the intelligence of school children
      in Madhya Pradesh, India.

PMID- 23546382
TI  - Authors' reply.

PMID- 23546383
TI  - An invisible sign stimulus: completion of occluded visual images in the Bengalese
      finch in an ecological context.
AB  - An object that includes occluded parts is sometimes perceived as a complete image
      and this phenomenon is known as amodal or visual completion. A sign stimulus is a
      minimum set of information that elicits a behavior, but this notion raises
      questions about whether animals ever engage in the behavior when they cannot see
      the occluded sign stimulus, but they can visually complete it. Male Bengalese
      finches engage in courtship behavior toward video images of female finches. We
      conducted three experiments with Bengalese finches to show both sign stimuli and
      visual completion function in an ecological context. We used three types of
      visual images recorded from female finches as stimuli: the head, the body, and
      the whole. Results showed that male Bengalese finches showed courtship behavior
      toward the head-occluded stimuli whereas they did not toward the headless body
      image. The results imply that the males completed this occluded sign stimulus
      through the process of visual completion. Exposure to a sign stimulus combined
      with the process of visual completion may operate cooperatively to facilitate
      adaptive responses under conditions of limited information.

PMID- 23546384
TI  - Multidentate zwitterionic chitosan oligosaccharide modified gold nanoparticles:
      stability, biocompatibility and cell interactions.
AB  - Surface engineering of nanoparticles plays an essential role in their colloidal
      stability, biocompatibility and interaction with biosystems. In this study, a
      novel multidentate zwitterionic biopolymer derivative is obtained from
      conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl
      phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles
      (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under
      extreme conditions including high salt conditions, wide pH range and serum or
      plasma containing media. The AuNPs also show strong resistance to competition
      from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate
      low cytotoxicity investigated by both MTT and LDH assays, and good
      hemocompatibility evaluated by hemolysis of human red blood cells. In addition,
      the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed
      that the AuNPs are uptaken by cells in a concentration dependent manner, and they
      can escape from endosomes/lysosomes to cytosol and tend to accumulate around the
      nucleus after 24 h incubation but few of them are excreted out of the cells. Gold
      nanorods are also stabilized by this ligand, which demonstrates robust dispersion
      stability and excellent hemocompatibility. This kind of multidentate zwitterionic
      chitosan derivative could be widely used for stabilizing other inorganic
      nanoparticles, which will greatly improve their performance in a variety of bio
      related applications.

PMID- 23546385
TI  - NeuroGPS: automated localization of neurons for brain circuits using L1
      minimization model.
AB  - Drawing the map of neuronal circuits at microscopic resolution is important to
      explain how brain works. Recent progresses in fluorescence labeling and imaging
      techniques have enabled measuring the whole brain of a rodent like a mouse at
      submicron-resolution. Considering the huge volume of such datasets, automatic
      tracing and reconstruct the neuronal connections from the image stacks is
      essential to form the large scale circuits. However, the first step among which,
      automated location the soma across different brain areas remains a challenge.
      Here, we addressed this problem by introducing L1 minimization model. We
      developed a fully automated system, NeuronGlobalPositionSystem (NeuroGPS) that is
      robust to the broad diversity of shape, size and density of the neurons in a
      mouse brain. This method allows locating the neurons across different brain areas
      without human intervention. We believe this method would facilitate the analysis
      of the neuronal circuits for brain function and disease studies.

PMID- 23546386
TI  - Different adaptations in AMPA receptor transmission in the nucleus accumbens
      after short vs long access cocaine self-administration regimens.
AB  - Ca(2+)-permeable AMPA receptors (CP-AMPARs) accumulate in the nucleus accumbens
      (NAc) after ~1 month of withdrawal from a long-access cocaine self-administration
      regimen (6 h/d, 10d). This is functionally significant because CP-AMPARs mediate
      the 'incubated' cue-induced cocaine craving produced by this regimen. Our present
      goal was to determine if other commonly employed cocaine self-administration
      regimens also elicit CP-AMPAR accumulation. We compared four regimens, named
      according to whether sessions were short-access (ShA, 2 h) or long-access (LgA, 6
      h) and the total number of sessions: LgA/10d (already shown to elicit CP-AMPAR
      accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latter regimens, rats
      began with 10 days of ShA and then entered a differential phase (10-14 days) in
      which ShA sessions either continued or switched to LgA. Controls self
      administered saline. After >40 days of withdrawal, whole-cell patch-clamp
      recordings were performed in NAc core medium spiny neurons to assess the
      contribution of CP-AMPAR transmission, based on the magnitude of synaptic
      suppression elicited by bath application of the selective CP-AMPAR antagonist
      naspm (100 MUM). Naspm produced a non-significant (~10%) attenuation of
      electrically evoked local excitatory postsynaptic current in the saline and ShA
      groups. By contrast, a significant naspm-induced synaptic attenuation (25-30%)
      was observed in both the LgA groups. Further analyses indicate that this
      emergence of CP-AMPAR transmission in the LgA groups is associated with increased
      baseline responsiveness of MSN to excitatory drive. Together with data on cocaine
      infusions in each group, our results show that CP-AMPAR accumulation and enhanced
      glutamate transmission is associated with longer sessions (6 h), rather than the
      number of sessions or cocaine infusions.

PMID- 23546388
TI  - "Benzation" of graphene upon addition of monovalent chemical species.
AB  - The chemical bonding analysis using the adaptive natural density partitioning
      method of the C4F fluorinated graphene sheet revealed a chemical bonding model
      explaining its particular stability. We proposed that the stability of the C4F
      fluorinated graphene is due to the so-called "benzation" of graphene. On the
      basis of our chemical bonding model we predicted that other high-symmetry
      structures of the C7F4, C3F2, C13F10, etc. stoichiometries, containing planar
      hexagons, which are separated from each other by 2, 3, 4, etc. C-F fragments
      could also possess additional stability. We also suggested that other
      functionalized graphene structures of the C4X and C7X4, C3X2, C13X10
      stoichiometries, where X is a monovalent atom (H, F, Cl) or a monovalent group
      (CN, CCH etc.), could also have extra stability. We hope that the developed
      model, obtained for the functionalization of pristine graphene, will give an
      impetus for experimentalists to devise methods, which could serve as useful tools
      for producing this kind of materials with the tailored properties.

PMID- 23546387
TI  - Cocaine cue-induced dopamine release in amygdala and hippocampus: a high
      resolution PET [18F]fallypride study in cocaine dependent participants.
AB  - Drug-related cues are potent triggers for relapse in people with cocaine
      dependence. Dopamine (DA) release within a limbic network of striatum, amygdala
      and hippocampus has been implicated in animal studies, but in humans it has only
      been possible to measure effects in the striatum. The objective here was to
      measure drug cue-induced DA release in the amygdala and hippocampus using high
      resolution PET with [(18)F]fallypride. Twelve cocaine-dependent volunteers (mean
      age: 39.6 +/- 8.0 years; years of cocaine use: 15.9 +/- 7.4) underwent two
      [(18)F]fallypride high-resolution research tomography-PET scans, one with
      exposure to neutral cues and one with cocaine cues. [(18)F]Fallypride non
      displaceable-binding potential (BPND) values were derived for five regions of
      interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative
      striatum, and sensorimotor striatum). Subjective responses to the cues were
      measured with visual analog scales and grouped using principal component
      analysis. Drug cue exposure significantly decreased BPND values in all five ROI
      in subjects who had a high-, but not low-, craving response (limbic striatum:
      p=0.019, associative striatum: p=0.008, sensorimotor striatum: p=0.004, amygdala:
      p=0.040, and right hippocampus: p=0.025). Individual differences in the cue
      induced craving response predicted the magnitude of [(18)F]fallypride responses
      within the striatum (ventral limbic: r=0.581, p=0.048; associative: r=0.589,
      p=0.044; sensorimotor: r=0.675, p=0.016). To our knowledge this study provides
      the first evidence of drug cue-induced DA release in the amygdala and hippocampus
      in humans. The preferential induction of DA release among high-craving responders
      suggests that these aspects of the limbic reward network might contribute to drug
      seeking behavior.

PMID- 23546389
TI  - DNA hypermethylation of a selective gene panel as a risk marker for colon cancer
      in patients with ulcerative colitis.
AB  - Patients with inflammatory bowel disease (IBD) which includes ulcerative colitis
      (UC) and Crohn's disease (CD) of the colon are at risk of developing colorectal
      cancer (CRC). Here, we analyzed the methylation status of selected genes as a
      risk marker in UC patients. We assessed methylation frequency of 4 genes
      [secreted frizzled-related protein 1 (SFRP1), transcription elongation regulator
      1-like (TCERG1L), fibrillin 2 (FBN2) and tissue factor pathway inhibitor 2
      (TFPI2)] in biopsies of 36 UC patients. SFRP1 and TCERG1L genes showed high
      methylation frequencies but FBN2 and TFPI2 genes showed methylation frequencies
      of 50% in UC patients which suggests that our sensitive selective markers could
      detect half of the UC patients. We also confirmed the methylation status in UC
      tissues by bisulfite sequencing analysis. We compared the levels of methylation
      in terms of quantification between UC patients and CRC tumors. Importantly,
      methylation levels of these 4 genes were found to be significantly higher in CRC
      compared to UC patients, even though we noted a frequent methylation pattern in
      UC patients. Our data suggest that sensitive DNA methylation markers are able to
      identify UC patients and this would implicate the risk of CRC. Therefore,
      assessing the methylation of these 4 genes in UC patients could contribute to
      prevent the progression of severe disease with regular colonoscopic surveillance.

PMID- 23546390
TI  - Are barriers in accessing health services in the Roma population associated with
      worse health status among Roma?
AB  - OBJECTIVES: The health of Roma has been found to be poorer than that of the
      majority population. The aim of this study was to explore the differences between
      Roma and non-Roma regarding perceived barriers in accessing health services.
      Furthermore, we aimed to assess the association between self-rated health status
      and Roma ethnicity and explore to what degree barriers in accessing health
      services explain this association. METHODS: We used data from the cross-sectional
      HepaMeta study conducted in 2011 in Slovakia. The final sample comprised 452 Roma
      (mean age 34.7; 35.2 % men) and 403 (mean age 33.5; 45.9 % men) non-Roma
      respondents. RESULTS: Roma ethnicity was found to be significantly associated
      with poorer self-rated health status. A considerable part of this association can
      be explained by barriers in accessing health services as perceived by Roma.
      CONCLUSIONS: Worse health in Roma is partially mediated by worse access to health
      services, apart from a large educational gap between Roma living in settlements
      and the majority population. Interventions should focus not only on health
      literacy among Roma but also on the health care system and health care
      professionals.

PMID- 23546391
TI  - Changes in family socio-economic status as predictors of self-efficacy in 13-year
      old Polish adolescents.
AB  - OBJECTIVES: The aim of this study is to determine the impact that raised mother's
      education and a relative change in family affluence might have on adolescent
      general self-efficacy (GSE). METHODS: Data on 600 children born in Poland in
      January 1995 and their families were used. Data from early childhood and
      adolescence (2008) were considered and the change between these two periods was
      determined. RESULTS: Family affluence increased in 37.3 % of families with
      mothers, who had raised their education level (12.6 % of the sample), in
      comparison to 26.8 % in the group with no change, p < 0.001. The average GSE
      scores in those groups were 73.4 and 68.1, respectively, p < 0.001. In the best
      linear regression model adjusted for gender, the independent predictors of GSE
      turned out to be mother's education change and the family's current affluence.
      CONCLUSIONS: Raised mother's education level may encourage building up
      developmental assets in older children. Based on the structural model, where self
      efficacy is the mediator of the relationship between socio-economic status change
      and the quality of life (KIDSCREEN-10) these results may be of importance in
      further research.

PMID- 23546392
TI  - Ilex kudingcha C.J. Tseng (Kudingcha) prevents HCl/ethanol-induced gastric injury
      in Sprague-Dawley rats.
AB  - Ilex kudingcha C.J. Tseng (kudingcha) is a traditional Chinese beverage widely
      consumed in East Asia. In the present study, the preventative effect of kudingcha
      on gastric injury was determined in Sprague-Dawley (SD) rats. High concentrations
      of kudingcha were observed to reduce the levels of the serum proinflammatory
      cytokines, interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha),
      compared with low concentrations of kudingcha. Gastric secretion volumes were
      highest in control rats and reduced in the following order; 250, 500 and 1,000
      mg/kg kudingcha-treated and normal rats. The pH levels of gastric juice samples
      obtained from each group revealed the opposite correlation. Gastric injury levels
      in rats treated with kudingcha were identified to be significantly reduced,
      demonstrating its anti-inflammatory properties. Administration of 1,000 mg/kg
      kudingcha (73.9%) by gavage was demonstrated to induce the highest inhibitory
      effect on gastric injury. Results of the current study indicate that kudingcha
      exhibits marked preventive effects on gastric injury.

PMID- 23546393
TI  - RPS12-specific shRNA inhibits the proliferation, migration of BGC823 gastric
      cancer cells with S100A4 as a downstream effector.
AB  - Our previous study using suppression subtractive hybridization (SSH), cDNA
      microarray and semi-quantitative RT-PCR showed that RPS12 was overexpressed in
      gastric cancer and it was closely related to metastasis. However, the role of
      RPS12 in gastric cancer is not clear, which led us to conduct the current study
      to further investigate the effects of RPS12 on the proliferation and migration of
      gastric cancer cells, and also to explore the underlying molecular mechanisms.
      RNA interference was used to inhibit the expression of RPS12. The expression of
      RPS12 and S100A4 in gastric cancer cells was determined using semi-quantitative
      RT-PCR and western blot analysis. Cell proliferation and migration were detected
      by MTT and transwell assay, respectively. In addition, the promoter activity of
      S100A4 was measured by a Dual-Luciferase Reporter Assay System. We found that
      RNAi-mediated RPS12 downregulation led to reduced proliferation and migration of
      BGC823 and SGC7901 gastric cancer cells. Further results showed that RPS12
      inhibition led to reduced S100A4 expression and decreased promoter activity of
      S100A4 in BGC823 cells. We demonstrated that ectopic expression of S100A4
      reversed the reduced proliferation and migration ability after RPS12 inhibition
      in BGC823 cells. Our findings provide the first demonstration that RPS12 plays
      important roles in regulating the proliferation and migration of gastric cancer
      cells. S100A4 can mediate the effects of RPS12 as a downstream effector.

PMID- 23546394
TI  - Serious adverse effects can occur with minor procedures: comment on "Risk of
      topical anesthetic-induced methemoglobinemia".

PMID- 23546395
TI  - Antimutagenic and genoprotective effects of Saraca asoca bark extract.
AB  - AIM OF THE STUDY: Traditionally herbal formulations have been used effectively
      for the management of disorders that are now being accepted worldwide. Saraca
      asoca bark extract (SAE) finds use in traditional herbal medicine. In the present
      study, SAE were studied for their antioxidant, antimutagenic, and antigenotoxic
      properties. METHODS: SAE were evaluated for antimutagenic property in Salmonella
      strains (TA97a, TA98, TA100, and TA102), in the presence and absence of metabolic
      activation (S9). The SAE was also studied for antigenotoxic property against
      cyclophosphamide (CP) in Swiss albino male mice in vivo. The extract was analyzed
      using high-performance liquid chromatography (HPLC). RESULTS: The study reveals
      antimutagenic property of the bark extract in Salmonella strains in the presence
      and absence of metabolic activation (S9). The study reports antigenotoxic
      property of the bark extract against CP in vivo. Thiobarbituric acid reactive
      species assay on the bark extract revealed antioxidant property. HPLC revealed
      the presence of two peaks corresponding to gallic acid and (-)-epicatechin,
      respectively. CONCLUSION: The study clearly reveals the antimutagenic and
      antigenotoxic properties of SAE.

PMID- 23546396
TI  - Randomly amplified polymorphic-DNA analysis for detecting genotoxic effects of
      Boron on maize (Zea mays L.).
AB  - This study was carried out to investigate the genotoxic effect of boron (B) on
      maize using randomly amplified polymorphic DNA (RAPD) method. Experimental design
      was conducted under 0, 5, 10, 25, 50, 100, 125, and 150 ppm B exposures, and
      physiological changes have revealed a sharp decrease in root growth rates from
      28% to 85%, starting from 25 ppm to 150 ppm, respectively. RAPD-polymerase chain
      reaction (PCR) analysis shows that DNA alterations are clearly observed from
      beginning to 100 ppm. B-induced inhibition in root growth had a positive
      correlation with DNA alterations. Total soluble protein, root and stem lengths,
      and B content analysis in root and leaves encourage these results as a
      consequence. These preliminary findings reveal that B causes chromosomal
      aberration and genotoxic effects on maize. Meanwhile, usage of RAPD-PCR technique
      is a suitable biomarker to detect genotoxic effect of B on maize and other crops
      for the future.

PMID- 23546397
TI  - Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol
      induced oxidative stress-mediated cytotoxicity in HepG2 cells.
AB  - The present investigations were carried out to study the protective potential of
      four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM),
      ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula
      coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known
      hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were
      pretreated with LCR, LCM, LCE, and LCL extracts (10-50 MUg/ml) of L.
      coronopifolia for 24 h and then ethanol was added and incubated further for 24 h.
      After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) and neutral red uptake assays and morphological
      changes in HepG2 cells were studied. Pretreatment with various extracts of L.
      coronpifolia was found to be significantly effective in countering the cytotoxic
      responses of ethanol. Antioxidant properties of these L. coronopifolia extracts
      against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and
      glutathione (GSH) levels induced by ethanol were investigated. Results show that
      pretreatment with these extracts for 24 h significantly inhibited ROS generation
      and LPO induced and increased the GSH levels reduced by ethanol. The data from
      the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia
      showed hepatoprotective activity against ethanol-induced damage in HepG2 cells.
      However, a comparative study revealed that the LCE extract was found to be the
      most effective and LCL the least effective. The hepatoprotective effects observed
      in the study could be associated with the antioxidant properties of these
      extracts of L. coronopifolia.

PMID- 23546398
TI  - Differential propensity of citrate- and polyethylene glycol-coated silver
      nanoparticles to bovine hemoglobin.
AB  - Propensity of two different silver nanoparticles (Ag-NPs) to bovine hemoglobin
      (BHb) was investigated by means of spectroscopic methods. We have combined
      spectrophotometric and calorimetric methods to show that there is no significant
      interaction between citrate-coated Ag-NPs and BHb at physiological pH and 20
      degrees C. However, our previous results show that polyethylene glycol-coated Ag
      NPs strongly bind to Hb and effect on the secondary and tertiary structures of
      BHb. Thus, a suitable surface coating and modification of surface charge would
      increase the NPs safety and reduce adverse biological responses. 

PMID- 23546399
TI  - Comparison between intracameral moxifloxacin administration methods by assessing
      intraocular concentrations and drug kinetics.
AB  - BACKGROUND: Studies have indicated that intracameral administration of
      moxifloxacin (MFLX), a fourth-generation fluoroquinolone, is safe and effective.
      However, administration methods vary between studies, and no definite protocol
      exists. A prospective study clarifying the incidence of endophthalmitis and
      complication rates associated with each administration method would require an
      extremely large sample size because endophthalmitis has a low incidence rate.
      Therefore, we investigated appropriate intracameral MFLX administration methods
      by assessing intraocular concentrations following simple injection and flushing,
      and by measuring drug kinetics (half-life). METHODS: Experiment 1: (human eyes).
      Irrigation (flushing) with 33.33 MUg/ml MFLX (150-fold dilution) and simple
      injection with 0.1 ml of 500 MUg/ml MFLX (10-fold dilution) were assessed after
      cataract surgery. Experiment 2: (rabbits: kinetics study). Flushing with 30-fold
      or 150-fold dilutions of MFLX was assessed. Aqueous humor samples (0.1 ml)
      obtained immediately after irrigation and 1, 3, and 5 h after irrigation were
      analyzed using high-performance liquid chromatography. RESULTS: Experiment 1:
      MFLX (500 MUg/ml) administered using simple injection in humans underwent a 3.3
      fold dilution (152.33 MUg/ml). Total anterior chamber displacement after flushing
      with 33.33 MUg/ml MFLX resulted in a concentration of 29.54 MUg/ml (90%
      displacement). Experiment 2: Concentrations at baseline were 52% at 1 and 15% at
      3 h respectively, suggesting that the half-life of intracameral MFLX was >1 h.
      CONCLUSIONS: Considering that the half-life of MFLX was >1 h, a final
      concentration of 150 MUg/ml results in a 2 h concentration of 38 MUg/ml, which
      was beyond the minimum inhibitory concentration required to inhibit the growth of
      90% of bacteria (MIC90) for most resistant pathogens. We postulate that a final
      concentration of 150 MUg/ml is considerably effective and safe. However, more
      resistant bacteria will evolve in the future, and the standard MIC90 may change
      accordingly. Therefore, even if a suitable concentration is determined, it may
      not necessarily remain constant. This effective concentration should be
      continually revised on the basis of safety and effectiveness assessments.

PMID- 23546400
TI  - Early retinopathy of prematurity findings identified with fluorescein
      angiography.
AB  - BACKGROUND: Fluorescein angiography has been fundamental for the understanding
      and description of vascular disorders affecting the retina and choroid. The aim
      of this report is to assess the early anatomic retinal changes visible with
      angiography, and their relation with the clinical findings of retinopathy of
      prematurity. METHODS: Ten babies were included in the study, the initial
      examination being at 2 weeks after birth. Two cycles of tropicamide 0.8 % and
      phenylephrine 5 % eye drops were instilled into both eyes 30 min before
      examination. A RetCam II was used to obtain digital retinal images, after
      instilling topical anesthesia (tetracain 0.5 %) and using a contact gel.
      Fluorescein angiography was undertaken following administration of an intravenous
      bolus of 0.1 ml/kg saline fluorescein 10 % followed by a 3.0-ml isotonic saline
      flush, with the assistance of the neonatologist; the right and left eyes were
      imaged. RESULTS: We observed that some of the vascular abnormalities described
      for threshold disease by Lepore were already present at the second week of life,
      preceding the diagnosis of threshold disease by 3-4 weeks in two cases. The main
      findings in our cases were arterio-venous shunts, surrounded by areas of
      capillary non-perfusion, rosary-bead-like hyper-fluorescence, tortuosity and
      leakage from distal arterioles, none of which were detectable in the digital
      fundus pictures. CONCLUSIONS: Early ROP screening at the NICU that includes FA is
      a safe procedure, and gives the examiner details of vascular changes that are not
      detectable by indirect ophthalmoscopy, which could predict the progression to
      threshold disease, and provide an alert about the need of therapeutic
      interventions.

PMID- 23546401
TI  - [American Trypanosomiasis (Chagas disease) in the municipality of Chilon,
      Chiapas: a clinicoepidemiologic survey].

PMID- 23546402
TI  - [Comment on the article "DNA mutations associated to rifampicin or isoniazid
      resistance in M. tuberculosis clinical isolates from Sonora, Mexico" by Enrique
      Bolado-Martinez and collaborators].

PMID- 23546403
TI  - [Response to comment on the article "DNA mutations associated to rifampicin or
      isoniazid resistance in M. tuberculosis clinical isolates from Sonora, Mexico" by
      Enrique Bolado-Martinez and collaborators].

PMID- 23546404
TI  - [Mortality from Rickettsia rickettsii spotted fever in patients at a pediatric
      hospital in the state of Sonora, 2004-2012].

PMID- 23546405
TI  - [Universal health coverage in Mexico: the persistent gaps].

PMID- 23546406
TI  - Association between light absorption measurements of PM2.5 and distance from
      heavy traffic roads in the Mexico City metropolitan area.
AB  - OBJECTIVE: To study the relationship between light absorption measurements of
      PM2.5 at various distances from heavy traffic roads and diesel vehicle counts in
      Mexico City. MATERIALS AND METHODS: PM2.5 samples were obtained from June 2003
      June 2005 in three MCMA regions. Light absorption (b abs) in a subset of PM2.5
      samples was determined. We evaluated the effect of distance and diesel vehicle
      counts to heavy traffic roads on PM2.5 b abs using generalized estimating
      equation models. RESULTS: Median PM2.5 b abs measurements significantly decrease
      as distance from heavy traffic roads increases (p<0.002); levels decreased by 7%
      (CI95% 0.9-14) for each 100 additional meters from heavy traffic roads. Our model
      predicts that PM2.5 b abs measurements would increase by 20% (CI95% 3-38) as the
      hourly heavy diesel vehicle count increases by 150 per hour. CONCLUSION: PM2.5 b
      abs measurements are significantly associated with distance from motorways and
      traffic density and therefore can be used to assess human exposure to traffic
      related emissions.

PMID- 23546407
TI  - HPV vaginal self-sampling among women non-adherent to Papanicolaou screening in
      Chile.
AB  - OBJECTIVE: To evaluate acceptance, preference and compliance with referral of
      vaginal self-sampling for the detection of Human papillomavirus (HPV) among women
      non-adherent to Papanicolaou (Pap) screening in Santiago, Chile. MATERIALS AND
      METHODS: Using multistage sampling we identified women aged 30-64 years who
      reported not receiving a Pap test in the previous three years and offered them
      Pap testing at the health center or vaginal self-sampling for HPV testing at
      home. Self-collected samples were analyzed with hybrid capture. All HPV+ women
      were referred for colposcopy, biopsy and treatment when needed. RESULTS: 1 254
      eligible women were contacted; 86.5% performed self-sampling and 8.1% refused;
      124 women were HPV+ (11.4%: 95%CI 9.6-13.5) of whom 85.5% attended colposcopy; 12
      had CIN2+ (1.1%: 95 %CI 0.5-1.7). CONCLUSION: HPV vaginal self-sampling can be
      easily implemented in Chile and could improve coverage, successfully reaching
      women who drop out of the screening program.

PMID- 23546408
TI  - [Local conditions of vulnerability associated with dengue in two communities of
      Morelos].
AB  - OBJECTIVE: To evaluate the vulnerability associated with the occurrence of dengue
      in two villages of Morelos, Mexico from 2006 to 2009. MATERIALS AND METHODS. A
      survey on knowledge, risk perception, prevention practices and water use was
      applied in two villages of Morelos. Using a principal component analysis, an
      index of local vulnerability to dengue (IVL) was constructed. The association of
      IVL with the disease at home was assessed using a Chi-square test. RESULTS: The
      IVL included five components explaining 63% of the variance and was classified in
      three categories: low, medium and high. There was a significant association
      between increased vulnerability and prevalence of reported cases of dengue in
      Temixco and Tlaquiltenango. CONCLUSION: The study of vulnerability to dengue
      allows us to identify local needs in the field of health promotion.

PMID- 23546409
TI  - [A qualitative study on health care to chronically ill people in Popular Health
      Insurance program].
AB  - OBJECTIVE: To examine health care provided to chronically ill people in the
      Popular Health Insurance (Seguro Popular) from the perspective of patients and
      health professionals. MATERIALS AND METHODS: A qualitative study was carried out
      in Guadalajara, Mexico. 40 chronically ill people, and 14 health professionals of
      primary health centers participated in the study. Information was gathered using
      semi-structured interviews; critical discourse analysis was carried out. RESULTS:
      Seguro Popular has meant gains and losses to participants. Cronically ill people
      value it positively since it is perceived as a gift, not a social right. Some
      obstacles impede participants accessing health care, obtaining medications and
      analysis. Conflictive relations also cause tensions between patients and health
      professionals. CONCLUSION: The initial goals of Seguro Popular are not achieved
      regarding health care to chronically ill people. The perspectives of sick people
      should be prioritized.

PMID- 23546410
TI  - [Problems of the health system in Mexican states with high incidence of maternal
      mortality].
AB  - OBJECTIVE: To identify and prioritize problems in states' health systems which
      limit the efficacy of interventions to prevent maternal mortality. MATERIALS AND
      METHODS: We made a conceptual mapping of priority problems perceived as such by
      communities of practice (COP) in four states with high ratios of maternal
      mortality in Mexico. Then, the four COP reviewed the literature and refined their
      formulation of previously identified problems. RESULTS: Priority problems focused
      on emergency obstetric care (EmOC), specifically: inadequate financial resources
      (Guerrero), substandard training among available EmOC providers (State of
      Mexico), inefficiencies in existing EmOC networks (Oaxaca) and inadequate
      knowledge of, and/or compliance to, standard EmOC protocols (Veracruz). The
      literature review confirmed the pertinence of problems previously identified by
      COP through conceptual mapping. CONCLUSIONS. The four COP showed a high level of
      congruency between their original perception of problems in the states' health
      systems and international scientific evidence. Identified problems and their
      reformulation based on evidence help identify solutions adaptable to local
      contexts.

PMID- 23546411
TI  - [Molecular detection of hepatitis E virus in pig livers destined for human
      consumption in the state of Nuevo Leon, Mexico].
AB  - OBJECTIVE: Molecular detection of HEV in pig livers destined for human
      consumption in Nuevo Leon, Mexico. MATERIALS AND METHODS: 87 livers were
      collected from pigs slaughtered in TIF and 40 livers from butchers. A 212 pb
      fragment of HEV ORF2 gene was amplified by semi-nested RT-PCR. RESULTS: 19.54%
      (17) of tif's and 22.5% (9) of butcher's livers were positive for HEV. Sequencing
      of the amplified products showed a 94%-95% homology with the sequences reported
      for genotype 3. CONCLUSIONS: Our results indicate that HEV is circulating in
      swine herds in the state, constituting a probable source of contamination of pig
      meat products.

PMID- 23546412
TI  - [Counseling interventions for smoking cessation: systematic review].
AB  - OBJECTIVE: A systematic review on efficacy and safety of smoking cessation
      counseling was developed. MATERIALS AND METHODS: The ADAPTE methodology was used
      with a search of Clinical Practice Guidelines (CPG) in Medline, EMBASE, CINAHL,
      LILACS, and Cochrane. DELBI was used to select CPG with score over 60 in
      methodological rigor and applicability to the Colombian health system. Smoking
      cessation rates at 6 months were assessed according to counseling provider,
      model, and format. In total 5 CPG out of 925 references were selected comprising
      44 systematic reviews and meta-analyses. RESULTS: Physician brief counseling and
      trained health professionals' intensive counseling (individual, group, proactive
      telephone) are effective with abstinence rates between 2.1% and 17.4%. Only
      practical counseling and motivational interview were found effective intensive
      interventions. The clinical effect of smoking cessation counseling is low and
      long term cessation rates uncertain. CONCLUSION: Cost-effectiveness analyses are
      recommended for the implementation of counseling in public health programs.

PMID- 23546413
TI  - [The quest for universal health coverage: achieving social protection for all in
      Mexico].

PMID- 23546415
TI  - What future does the pharmaceutical industry have in the cardiovascular world?

PMID- 23546416
TI  - Plasma driven ammonia decomposition on a Fe-catalyst: eliminating surface
      nitrogen poisoning.
AB  - Strongly adsorbed N atoms inhibit the ammonia decomposition reaction rate. Plasma
      driven catalysis can solve this problem and increase the ammonia conversion from
      7.8% to 99.9%. (15)NH(3) isotope tracing and optical emission spectroscopy show
      that gas-phase active species (NH(3)*, NH) in the plasma zone facilitate the
      desorption step by an Eley-Rideal (E-R) interaction.

PMID- 23546417
TI  - Beyond the SYNTAX score--advantages and limitations of other risk assessment
      systems in left main percutaneous coronary intervention.
AB  - Risk stratification is an emerging topic in the modern management of patients
      with left main disease referred for percutaneous coronary intervention (PCI).
      Recent years have witnessed an explosive multiplication of risk models for
      prognostic stratification in complex PCI. Many of this models deal with
      modification of the angiographic SYNTAX score, or seek to overcome its known
      pitfalls and limitations, including lack of clinical and functional information,
      inter- and intra-observer variabilities, and poor calibration. Risk scoring
      systems beyond the SYNTAX score may be classified into angiographic (residual
      SYNTAX score, coronary artery bypass grafting SYNTAX score), clinical (EuroSCORE
      I and II, ACEF score and modified ACEF scores), combined clinical and
      angiographic (Global Risk Classification, Clinical SYNTAX score, logistic
      Clinical SYNTAX score, SYNTAX score II) and functional (Functional SYNTAX score).
      This article reviews current concepts in risk modeling and explores the
      advantages and limitations of the alternatives to the SYNTAX score in patients
      undergoing left main PCI. 

PMID- 23546419
TI  - Effects of encapsulated Lactobacillus acidophilus along with pasteurized longan
      juice on the colon microbiota residing in a dynamic simulator of the human
      intestinal microbial ecosystem.
AB  - The effect of encapsulated Lactobacillus acidophilus LA5 along with pasteurized
      longan juice on the colon microbiota was investigated by applying a dynamic model
      of the human gastrointestinal tract. Encapsulated L. acidophilus LA5 in
      pasteurized longan juice or sole encapsulated L. acidophilus LA5 exhibited the
      efficiency of colonizing the colon and enabling the growth of colon lactobacilli
      as well as beneficial bifidobacteria but inhibited the growth of fecal coliforms
      and clostridia. Moreover, these treatments gave rise to a significant increase of
      lactic acid and short-chain fatty acids such as acetate, propionate, and
      butyrate. Although acetate displayed the highest quantity, it was likely that
      after incorporating encapsulated L. acidophilus LA5 plus pasteurized longan
      juice, quantity of butyrate exceed propionate, and acetate in comparison with
      their controls. Denaturant gradient gel electrophoresis patterns confirmed that
      various treatments affected the alteration of microbial community within the
      simulator of the human intestinal microbial ecosystem. 

PMID- 23546420
TI  - Investigation of antimicrobial physiology of orthorhombic and monoclinic
      nanoallotropes of sulfur at the interface of transcriptome and metabolome.
AB  - Nanosized elemental sulfur (ES) is already reported to exert superior
      antimicrobial efficacy than micron-sized ES, which encourages their use in drugs
      and therapeutics. The aim of the present study is to explore the possible route
      and mode of antimicrobial action of orthorhombic (alpha-SNPs) and monoclinic
      (beta-SNPs) allotropes of sulfur, respectively, at their nano-dimensions. The
      antimicrobial efficacy of alpha- and beta-SNPs was determined against both the
      conventionally ES-resistant and ES-susceptible fungi and bacteria. Both the SNPs
      inhibited the microbial growth, irrespective of their resistance profile to ES
      and caused significant deformities on the microbial cell surfaces. However, the
      extent of antimicrobial efficacy was found to be optimum for alpha-SNPs, which
      can be attributed to their size, shape, and surface modification. Subsequent
      transcript profiling, metabolite profiling, and enzymatic analyses revealed that
      alpha- and beta-SNPs impaired a cluster of mitochondrial enzymes involved in
      cellular respiration and oxidative phosphorylation. ES and SNPs stress were found
      to elicit the NADPH-dependent glutathione reductase mediated ES-detoxification
      response in fungi and caused them to undertake the glyoxylate shunt in favor of
      energy conservation. A simultaneous study was also undertaken to assess the
      biocompatible or bio-adverse properties of SNPs in terms of their cytotoxic and
      genotoxic effects against the human derived lung fibroblast cell line (MRC-5).
      The present study hence explores the antimicrobial physiology of two novel
      functional materials and demonstrates their compatibility as a future putative
      antimicrobial drug.

PMID- 23546421
TI  - Differentiation of species of the genus Saccharomyces using biomolecular
      fingerprinting methods.
AB  - The genus Saccharomyces comprises very closely related species. This high degree
      of relationship makes a simple identification and differentiation of strains
      difficult since these species are hardly discriminable by their morphological and
      physiological features. A sequence analysis of ribosomal DNA and the
      corresponding internal transcribed spacers can only rarely be successfully
      applied. In this study, we proved the applicability of a novel DNA fingerprinting
      method, the SAPD-PCR (specifically amplified polymorphic DNA) and of MALDI-TOF-MS
      (matrix-assisted laser desorption ionization time-of-flight mass spectrometry)
      fingerprinting with the MALDI Biotyper for the differentiation of species
      belonging to the genus Saccharomyces. It was possible with SAPD-PCR to create
      specific banding patterns for all Saccharomyces species. Different strains of the
      same species produced nearly the same banding patterns. Specific and reproducible
      reference spectra could be generated for each of the strains with the MALDI
      Biotyper. Therefore, SAPD-PCR and MALDI-TOF-MS can be fast and reliable tools to
      identify these related Saccharomyces species which are applied in many
      biotechnological processes.

PMID- 23546422
TI  - Bacterial metabolism of environmental arsenic--mechanisms and biotechnological
      applications.
AB  - Arsenic causes threats for environmental and human health in numerous places
      around the world mainly due to its carcinogenic potential at low doses. Removing
      arsenic from contaminated sites is hampered by the occurrence of several
      oxidation states with different physicochemical properties. The actual state of
      arsenic strongly depends on its environment whereby microorganisms play important
      roles in its geochemical cycle. Due to its toxicity, nearly all organisms possess
      metabolic mechanisms to resist its hazardous effects, mainly by active extrusion,
      but also by extracellular precipitation, chelation, and intracellular
      sequestration. Some microbes are even able to actively use various arsenic
      compounds in their metabolism, either as an electron donor or as a terminal
      electron acceptor for anaerobic respiration. Some microorganisms can also
      methylate inorganic arsenic, probably as a resistance mechanism, or demethylate
      organic arsenicals. Bioavailability of arsenic in water and sediments is strongly
      influenced by such microbial activities. Therefore, understanding microbial
      reactions to arsenic is of importance for the development of technologies for
      improved bioremediation of arsenic-contaminated waters and environments. This
      review gives an overview of the current knowledge on bacterial interactions with
      arsenic and on biotechnologies for its detoxification and removal.

PMID- 23546423
TI  - Regulation of poly-(R)-(3-hydroxybutyrate-co-3-hydroxyvalerate) biosynthesis by
      the AtoSCDAEB regulon in phaCAB+ Escherichia coli.
AB  - AtoSC two-component system (TCS) upregulates the high-molecular weight poly-(R)-3
      hydroxybutyrate (PHB) biosynthesis in recombinant phaCAB (+) Escherichia coli
      strains, with the Cupriavidus necator phaCAB operon. We report here that AtoSC
      upregulates also the copolymer P(3HB-co-3HV) biosynthesis in phaCAB (+) E. coli.
      Acetoacetate-induced AtoSC maximized P(3HB-co-3HV) to 1.27 g/l with a 3HV
      fraction of 25.5 % wt. and biopolymer content of 75 % w/w in a time-dependent
      process. The atoSC locus deletion in the ?atoSC strains resulted in 4.5-fold
      P(3HB-co-3HV) reduction, while the 3HV fraction of the copolymer was restricted
      to only 6.4 % wt. The ?atoSC phenotype was restored by extrachromosomal
      introduction of AtoSC. Deletion of the atoDAEB operon triggered a significant
      decrease in P(3HB-co-3HV) synthesis and 3HV content in ?atoDAEB strains. However,
      the acetoacetate-induced AtoSC in those strains increased P(3HB-co-3HV) to 0.8
      g/l with 21 % 3HV, while AtoC or AtoS expression increased P(3HB-co-3HV)
      synthesis 3.6- or 2.4-fold, respectively, upon acetoacetate. Complementation of
      the ?atoDAEB phenotype was achieved by the extrachromosomal introduction of the
      atoSCDAEB regulon. Individual inhibition of beta-oxidation and mainly fatty acid
      biosynthesis pathways by acrylic acid or cerulenin, respectively, reduced P(3HB
      co-3HV) biosynthesis. Under those conditions, introduction of atoSC or atoSCDAEB
      regulon was capable of upregulating biopolymer accumulation. Concurrent
      inhibition of both the fatty acid metabolic pathways eliminated P(3HB-co-3HV)
      production. P(3HB-co-3HV) upregulation in phaCAB (+) E. coli by AtoSC signaling
      through atoDAEB operon and its participation in the fatty acids metabolism
      interplay provide additional perceptions of AtoSC critical involvement in E. coli
      regulatory processes towards biotechnologically improved polyhydroxyalkanoates
      biosynthesis.

PMID- 23546424
TI  - Bioaugmentation accelerates the shift of bacterial community structure against
      shock load: a case study of coking wastewater treatment by zeolite-sequencing
      batch reactor.
AB  - Bioaugmentation with degrading bacteria is an effective method to improve the
      treatment of refractory industrial wastewater; nevertheless there were
      controversial opinions about the fate of inoculated bacteria and microbial
      community dynamics. In this study, two lab-scale sequencing batch reactors filled
      with modified zeolite were used to treat a coking wastewater with pyridine and
      quinoline shock load, and a bacterial consortium containing three degrading
      strains was added in one reactor for bioaugmentation. During 120-day operation,
      the bioaugmented reactor removed over 99 % pyridine, 99 % quinoline, 85 % TOC, 65
      % COD, and 95 % NO3---N with higher resistance to the shock load than the non
      bioaugmented reactor. Based on the terminal restriction fragment length
      polymorphism of 16S rDNA, bacterial community diversity increased in the
      bioaugmented reactor. Principal component analysis revealed that, to cope with
      the shock load, the indigenous bacterial community recovered to the initial
      structure by acclimatizing itself constantly to the inhospitable environment; but
      bioaugmentation accelerated the shift of whole bacterial community, resulting in
      a far different structure from the initial one. Canonical correspondence analysis
      indicated that the environmental parameters of pyridine, quinoline, TOC, and NO3-
      -N had close negative correlations with bioaugmentation; and NH3--N and COD were
      the main parameters to impact on the bacterial community changes and treatment
      efficiency.

PMID- 23546426
TI  - The necessity of simple X-ray examination: a case report of button battery
      migration into the nasal cavity.
AB  - BACKGROUND: Since the discovery of button battery, it has been widely applied in
      various electric devices. However, the button battery has a potential risk as a
      foreign body in the nasopharyngeal field. Thus, there is a need for early
      diagnosis and removal of these batteries. METHODS: We experienced a case of
      foreign body in the nasal cavity. A battery was lost around a 2-year-old patient.
      He visited a local pediatric clinic. X-ray examination of the neck, chest. and
      abdomen showed no sign of a foreign body. He subsequently exhibited left cheek
      swelling and came to our clinic. RESULTS: X-ray examination of head revealed a
      metallic foreign body in the left nasal cavity. The foreign body was approached
      using an endoscope under general anesthesia. The nasal cavity was filled with
      necrotic tissue. We removed the foreign body using forceps. After surgery,
      perforation of nasal cavity was identified. CONCLUSIONS: The button battery was a
      potential risk because it contained toxic substances, could release an electrical
      current, and exerted direct pressure on the surrounding tissues. Surgical removal
      of button battery is the treatment of first choice. As for late complications,
      saddle nose is reported. Our patient would receive nasoplastic surgery around the
      age of 18 years. In summary, our patient's nose was not initially examined using
      x-ray study. It is very important to keep in mind the possibility of a nasal
      foreign body, not only for ear, nose, and throat doctors but also for
      pediatricians.

PMID- 23546425
TI  - Ku70 and ku80 null mutants improve the gene targeting frequency in Monascus ruber
      M7.
AB  - Normally, gene targeting by homologous recombination occurs rarely during a
      transformation process since non-homologous recombination is predominant in
      filamentous fungi. In our previous researches, the average gene replacement
      frequency (GRF) in Monascus ruber M7 was as low as 15 %. To develop a highly
      efficient gene targeting system for M. ruber M7, two M. ruber M7 null mutants of
      ku70 (MrDeltaku70) and ku80 (MrDeltaku80) were constructed which had no apparent
      defects in the development including vegetative growth, colony phenotype,
      microscopic morphology and spore yield compared with M. ruber M7. In addition,
      the production of some significant secondary metabolites such as pigments and
      citrinin had no differences between the two disruptants and the wild-type strain.
      Further results revealed that the GRFs of triA (encoding a putative
      acetyltransferase) were 42.2 % and 61.5 % in the MrDeltaku70 and MrDeltaku80
      strains, respectively, while it was only about 20 % in M. ruber M7. Furthermore,
      GRFs of these two disruptants at other loci (the pigE, fmdS genes in MrDeltaku70
      and the ku70 gene in MrDeltaku80) were investigated, and the results indicated
      that GRFs in the MrDeltaku70 strain and the MrDeltaku80 strain were doubled and
      tripled compared with that in M. ruber M7, respectively. Therefore, the ku70 and
      ku80 null mutants of M. ruber M7, especially the ku80-deleted strain, will be
      excellent hosts for efficient gene targeting.

PMID- 23546427
TI  - Massive hemoptysis in a post-Fontan procedure patient.
AB  - Aortopulmonary collateral vessels (AP collaterals) are frequently seen in
      patients with cyanotic heart disease. However, massive hemoptysis leading to life
      threatening hemorrhage is rare. In this case, we present a 7-year-old girl who
      presented to the pediatric emergency department with massive hemoptysis secondary
      to AP collateral hemorrhage. We were able to control her hemoptysis initially
      through calming techniques, but the patient eventually went on to have 2 cardiac
      catherization procedures, during which coiling of many AP collateral vessels was
      performed.

PMID- 23546428
TI  - An uncommon Salter-Harris I fracture of the distal femoral physis with marked
      epiphyseal dislocation.
AB  - This is a report of an uncommon Salter-Harris I fracture of the distal femoral
      physis with complete dislocation of the distal epiphysis. These fractures are
      most frequently sustained during sports injuries, with motor vehicle accidents as
      another leading cause. They are at high risk of nonanatomic healing with
      subsequent varus or valgus deformity or premature growth arrest of the physis
      with subsequent leg length difference. Although certain fractures of the distal
      femoral physis may be very rarely encountered in the emergency department, the
      unavailability of appropriate consult service or risk of vascular compromise may
      necessitate reduction by the emergency physician. This fracture-dislocation was
      reduced with intravenous opioid analgesia, gentle traction along the axis of the
      lower extremity, and firm but gentle manual reduction of the proximal femoral
      fragment. External casts alone have a high rate of failure in sustaining anatomic
      alignment, so percutaneous pinning is recommended as the definitive treatment.
      After reduction, this patient was transferred to a pediatric hospital capable of
      performing the necessary operative fixation.

PMID- 23546429
TI  - Reducing the time in making the diagnosis and improving workflow with point-of
      care ultrasound.
AB  - BACKGROUND: During the past decade, point-of-care ultrasound (POC US) has been
      increasingly performed in emergency medicine for a variety of indications.
      However, pediatric emergency physicians have been slower to understand the
      importance of POC US in the diagnosis of critical care cases. OBJECTIVE: This
      study aimed to illustrate the usefulness of POC US in improving workflow in the
      emergency department (ED) with an early diagnosis in a critically ill child by a
      pediatric emergency attending physician. CASE: On arrival to the ED, an early
      diagnosis of intussusception was made using real-time POC US by a pediatric
      emergency medicine attending physician well trained in pediatric US. CONCLUSIONS:
      This report illustrates the impact that POC US can make during an early diagnosis
      of intussusception. With thorough knowledge of the US features characteristic of
      intussusception, its accurate diagnosis using POC US has the potential to reduce
      morbidity and mortality as well as improve patient flow and throughput time in
      the ED.

PMID- 23546430
TI  - Subconjunctival hemorrhages in infants and children: a sign of nonaccidental
      trauma.
AB  - Subconjunctival hemorrhages in infants and children can be a finding after
      nonaccidental trauma. We describe 14 children with subconjunctival hemorrhages on
      physical examination, who were subsequently diagnosed by a child protection team
      with physical abuse. Although infrequent, subconjunctival hemorrhage may be
      related to abuse. Nonaccidental trauma should be on the differential diagnosis of
      subconjunctival hemorrhage in children, and consultation with a child abuse
      pediatrics specialist should be considered.

PMID- 23546431
TI  - Spontaneous spinal epidural hematoma in a teenage boy with cholestasis: a case
      report.
AB  - Spontaneous spinal epidural hematoma (SSEH) is a rare condition, often causing
      significant neurologic morbidity owing to its insidious nature and difficulty in
      diagnosis. Initial nonspecific clinical findings make the timely diagnosis
      challenging. A variety of underlying etiologies predispose patients to SSEH such
      as anticoagulation therapy, bleeding diatheses, vascular malformations, tumors,
      as well as spontaneous and idiopathic cases. Early diagnosis and intervention are
      critical for optimal patient outcomes. Here, we present a case of SSEH where
      coagulopathy was originating from underlying cholestasis. This, to our knowledge,
      represents the first case reported in the literature where a primary cholestatic
      disease is the underlying etiology.

PMID- 23546432
TI  - Use of conivaptan for refractory syndrome of inappropriate secretion of
      antidiuretic hormone in a pediatric patient.
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the
      most common form of hyponatremia in hospitalized patients. The available
      treatment options for SIADH are limited and not completely effective. A more
      recent and specific option for treatment of hyponatremia secondary to SIADH are
      the vasopressin-receptor antagonists. Conivaptan, an intravenous vasopressin
      receptor antagonist, is Food and Drug Administration approved for the treatment
      of euvolemic and hypervolemic hyponatremia in adults; however, data regarding its
      use in pediatric patients are extremely limited. Conivaptan played an integral
      role in the treatment of hyponatremia in this situation when conventional
      treatment modalities were ineffective. This patient did not experience any
      adverse effects, and his sodium level corrected slowly over a 24-hour period,
      avoiding complications of rapid sodium correction.

PMID- 23546433
TI  - A "shocking" appendicitis.
AB  - We report a case of Klebsiella oxytoca sepsis as a complication of nonperforated
      appendicitis in an 11-year-old immunocompetent boy. Even if septicemia is not
      mentioned in major reviews as a complication of nonperforated appendicitis,
      several cases have occasionally been reported in adult patients in the
      literature. The pathogenesis of sepsis with nonperforated appendicitis is still
      not clear, but a mechanism of bacterial translocation has been taken into account
      to explain the spread of microorganisms from the intestinal lumen to the systemic
      blood stream. Clinicians should therefore be aware of this occurrence.

PMID- 23546434
TI  - Encephalitis.
AB  - Encephalitis is a serious and potentially treatable infection of the central
      nervous system. A pathogen is identified in less than 50% of cases. The
      differential diagnosis includes acute infection, immune-mediated causes, and
      other central nervous system processes. Emergent investigations include blood
      work, cerebrospinal fluid analysis, and neuroimaging. Empiric acyclovir and
      antibiotics should be started immediately to maximize the child's chance of
      neurologic recovery.

PMID- 23546436
TI  - Applications of nitrous oxide for procedural sedation in the pediatric
      population.
AB  - OBJECTIVE: The objective of this review was to provide a general descriptive
      account of the physical properties, end-organ effects, therapeutic applications,
      and delivery techniques of nitrous oxide (N2O) as used in the arena of procedural
      sedation. DATA SOURCE: A computerized bibliographic search regarding the
      applications of nitrous for provision of sedation and analgesia during procedures
      with an emphasis on the pediatric population was performed. RESULTS: The end
      organ effects of N2O have been well described in the operating room setting.
      Aside from its effects on the central nervous system of sedation and analgesia,
      N2O may alter intracerebral dynamics and alter cerebral blood flow and
      intracranial pressure especially in patients with altered intracranial
      compliance. Effects on ventilation include a dose-related depression of
      ventilatory function and control of upper airway patency. These effects are
      generally limited in the absence of comorbid diseases and potentiated by other
      sedative and analgesic agents. The more clinically significant respiratory effect
      of N2O on ventilatory function is a dose-dependent depression of the ventilatory
      response to hypoxemia. Hemodynamic effects include a mild direct depressant
      effect on myocardial function, which in the absence of comorbid cardiac disease
      is generally compensated by stimulation of the sympathetic nervous system.
      Nitrous oxide may potentially aggravate pulmonary hypertension. Additional
      physiologic effects on neurologic and hematologic function may result in
      inactivation of the enzyme, methionine synthetase. Recent concern has also been
      raised regarding the potential effects of N2O on immune function and its
      relationship to perioperative surgical site infections. Given differences in the
      solubility, N2O will diffuse into and significantly expand gas-filled cavities.
      Chronic exposure of health care works to N2O is also a concern. Although there
      are limited data in the literature to clearly substantiate concerns regarding the
      reproductive toxicity of occupational exposure to N2O, appropriate scavenging and
      use of other techniques are mandatory. Nitrous oxide has been shown to be
      effective for a variety of minor surgical procedures such as venipuncture,
      intravenous cannula placement, lumbar puncture, bone marrow aspiration,
      laceration repair, dental care, and minor dermatologic procedures. It is
      generally as effective as midazolam, with several studies demonstrating it to be
      more effective. However, its utility is not as great in severely painful
      procedures such as fracture reduction. Demonstrated advantages to parenteral
      sedation include a more rapid onset and a shorter recovery time with the majority
      of patients preferring it to over other agents or agreeing to its use for
      subsequent procedures. The literature also suggests increased success rates with
      simple procedures such as intravenous cannula placement when compared with
      placebo. In general, life-threatening adverse events have not been reported. Most
      common adverse effects include dysphoria and vomiting. For more painful
      procedures, combination with another agent may be used, and in all cases, topical
      or infiltrative local anesthesia is recommended. CONCLUSIONS: In general, N2O is
      a useful adjunct for procedural sedation. Given the variety of procedures
      performed in the pediatric patient, ongoing research is required to identify the
      most appropriate and effective use of this agent. This may be particularly
      relevant when evaluating its use for procedures associated with significant pain.
      In these scenarios, the combination of N2O with other agents needs to be
      evaluated. Given the potential for adverse effects, strict adherence to published
      guidelines regarding procedural sedation and monitoring is suggested.

PMID- 23546437
TI  - Pediatric emergency medicine: legal briefs.

PMID- 23546438
TI  - ECGs in the ED.

PMID- 23546439
TI  - Gas-assisted growth of boron-doped nickel nanotube arrays: rapid synthesis,
      growth mechanisms, tunable magnetic properties, and super-efficient reduction of
      4-nitrophenol.
AB  - Highly ordered noncrystalline boron-doped nickel nanotube arrays are rapidly
      synthesized within 150 s by template-based electroless deposition. The as
      prepared nanotubes have tunable magnetic properties and exhibit super efficient
      catalytic activity (~70 s) for the reduction of 4-nitrophenol.

PMID- 23546440
TI  - Key reconciliation for high performance quantum key distribution.
AB  - Quantum Key Distribution is carving its place among the tools used to secure
      communications. While a difficult technology, it enjoys benefits that set it
      apart from the rest, the most prominent is its provable security based on the
      laws of physics. QKD requires not only the mastering of signals at the quantum
      level, but also a classical processing to extract a secret-key from them. This
      postprocessing has been customarily studied in terms of the efficiency, a figure
      of merit that offers a biased view of the performance of real devices. Here we
      argue that it is the throughput the significant magnitude in practical QKD,
      specially in the case of high speed devices, where the differences are more
      marked, and give some examples contrasting the usual postprocessing schemes with
      new ones from modern coding theory. A good understanding of its implications is
      very important for the design of modern QKD devices.

PMID- 23546441
TI  - Protective effect of lentivirus-mediated siRNA targeting ADAMTS-5 on cartilage
      degradation in a rat model of osteoarthritis.
AB  - The etiology of osteoarthritis (OA) is complex and multifaceted. Osteoarthritis
      is a chronic and progressive disease of the joints that is characterized by the
      degradation of articular cartilage. A disintegrin and metalloproteinase with
      thrombospondin motifs-5 (ADAMTS-5) is the major aggrecanase in cartilage. The aim
      of this study was to evaluate the effect of ADAMTS-5 knockdown on cartilage
      degradation. Rat articular chondrocytes were transfected with lentivirus-mediated
      ADAMTS-5 small interfering RNA (siRNA) or with empty vector control plasmid DNA
      (as the control). The suppression efficiency was measured using real-time
      polymerase chain reaction (RT-PCR) and western blot analysis. We then selected
      the most effective siRNA (siRNA1) and constructed the lentivirus-mediated siRNA
      targeting ADAMTS-5 for stable transfection. An animal model of OA was created
      using male Sprague-Dawley rats. OA was induced by performing anterior cruciate
      ligament transection (ACL-T) and partial medial meniscectomy (PM). The animals
      (n=80, weight 250-300 g) received an intra-articular injection of the empty
      vector control plasmid DNA or lentivirus-mediated ADAMTS-5 siRNA1 (20 ul, 1x108
      TU/ml). The progression of OA was analyzed using Osteoarthritis Research Society
      International (OARSI) scores. Compared with the control, ADAMTS-5 gene expression
      was decreased by approximately 80% by siRNA1 in a monolayer culture of
      chondrocytes. The intra-articular injection of lentivirus-mediated ADAMTS-5
      siRNA1 in vivo resulted in the downregulation of ADAMTS-5 protein expression and
      improved OARSI scores (p<0.05). A single injection of lentivirus-mediated ADAMTS
      5 siRNA prevented the degradation of articular cartilage. This method may provide
      a novel therapeutic strategy for the treatment of human OA.

PMID- 23546442
TI  - Risk factors. One less excuse for not quitting smoking.

PMID- 23546443
TI  - Atrial fibrillation: Anticoagulation for AF: can we GRASP-AF patients?

PMID- 23546444
TI  - Position statement of the World Heart Federation on the prevention and control of
      rheumatic heart disease.
AB  - In the 21(st) century, rheumatic fever (RF) and rheumatic heart disease (RHD) are
      neglected diseases of marginalized communities. Globally, RHD remains the most
      common cardiovascular disease in young people aged <25 years. Although RF and RHD
      have been almost eradicated in areas with established economies, migration from
      low-income to high-income settings might be responsible for a new burden of RHD
      in high-income countries. The World Heart Federation (WHF) and its Working Group
      on RF and RHD unites global experts, combines their experience and enthusiasm,
      and provides a platform for RHD control. This paper is a declaration of the WHF
      institutional strategic goal--a 25% reduction in premature deaths from RF and RHD
      among individuals aged <25 years by the year 2025. The position statement affirms
      WHF commitments to five key strategic targets: comprehensive register-based
      control programmes, global access to benzathine penicillin G, identification and
      development of public figures as 'RHD champions', expansion of RHD training hubs,
      and support for vaccine development. In this paper, we also review existing
      barriers to RF and RHD control and identify the actions required to change the
      trajectory of control for these diseases. This approach provides the foundation
      for governments, civil society, patient advocates, clinicians, researchers, and
      funding agencies to develop partnerships and unify global efforts to control RF
      and RHD. The WHF plans to expand this position statement to an operational plan
      that will be founded on science, research, and quantifiable progress indicators
      to impact positively on the millions of people who are affected by RHD and its
      long-term sequelae.

PMID- 23546445
TI  - Heart failure: Aldosterone antagonism for HFpEF.

PMID- 23546446
TI  - Dyslipidaemia: Failure to THRIVE: the end for niacin?

PMID- 23546447
TI  - Coronary artery disease: a gene-expression score to predict obstructive CAD.

PMID- 23546448
TI  - Self-assembly of semiconductor/insulator interfaces in one-step spin-coating: a
      versatile approach for organic field-effect transistors.
AB  - Self-assembly of interfaces is of great interest in physical and chemical
      domains. One of the most challenging targets is to obtain an optimal interface
      structure showing good electronic properties by solution-processing. Interfaces
      of semiconductor/semiconductor, semiconductor/insulator and insulator/insulator
      have been successfully manipulated to obtain high-performance devices. In this
      review we discuss a special class of interface, semiconductor/insulator
      interface, formed by vertical phase separation during spin-coating and focus on
      the versatile applications in organic field-effect transistors (OFETs). The
      formation of such an interface can be finished within tens of seconds and its
      mechanism is related to the materials, surfaces and dynamics. Fascinatingly, such
      self-assembly could be used to simplify the fabrication procedure, improve film
      spreading, change interfacial properties, modify semiconductor morphology, and
      encapsulate thin films. These merits lead to OFETs with high performance and good
      reliability. Also, the method is very suitable for combining with other solution
      processed techniques such as patterning and post-annealing, which leads to facile
      paper electronics, in situ purification and single crystal formation. Research on
      this topic not only provides an in-depth understanding of self-assembly in
      solution processing, but also opens new paths towards flexible organic
      electronics.

PMID- 23546449
TI  - Scutellarin inhibits the growth and invasion of human tongue squamous carcinoma
      through the inhibition of matrix metalloproteinase-2 and -9 and alphavbeta6
      integrin.
AB  - Scutellarin can inhibit the growth and migration of tongue cancer cells in vitro
      and can regulate cell adhesion; such agents will be the next generation
      anticancer therapeutics. In this study, we evaluated the antitumor effects of the
      scutellarin on human tongue squamous carcinoma (SAS) cell line and investigated
      its molecular mechanism. To explore the possible mechanisms underlying the
      antitumor effect of scutellarin, we studied its impact on the growth and invasion
      of SAS cells xenografted into nude mice, on the expression of MMP-2, MMP-9,
      integrin alphavbeta6, and c-JUN, and also on changes in collagen fibers. We
      observed that the growth of xenograft SAS tumors in nude mice was significantly
      inhibited by the administration of scutellarin without major adverse effects.
      Results showed that scutellarin mediated inhibition of tumor cell proliferation,
      induced apoptosis, and regulated expression of matrix metallo-proteinase (MMP)-2
      and -9, and integrin alphavbeta6 at the mRNA and protein levels in vivo.
      Moreover, scutellarin regulated the expression of collagen fibers in the tumor
      microenvironment (surrounding the tumor), thereby inhibiting cell invasion and
      metastasis. Our in vitro and in vivo studies have shown that scutellarin reduces
      the expression of MMP-2 and -9, and integrin alphavbeta6 in SAS cells, possibly
      through the regulation of expression of transcription factor AP-1. These results
      suggest that scutellarin can have an anti-tumor therapeutic effect by inhibition
      of the ability of SAS cells to invade and metastasize.

PMID- 23546450
TI  - miRNA-200c increases the sensitivity of breast cancer cells to doxorubicin
      through the suppression of E-cadherin-mediated PTEN/Akt signaling.
AB  - Doxorubicin (ADR) is successfully used to treat breast cancer, however, it is
      often associated with the acquired resistance of breast cancer cells which
      eliminates the therapeutic efficiency of ADR, leading to relapse and a poorer
      prognosis. It has been reported that microRNA-200c (miRNA-200c), a non-coding
      RNA, is important in the epithelial to mesenchymal transition (EMT) and
      metastasis in breast cancer cells. Recent evidence demonstrated that miRNA-200c
      is also regulated in chemotherapeutic drug resistance, however, the precise
      mechanism by which this occurs remains unclear. In this study, we demonstrated
      that the loss of miRNA-200c correlates with the acquired resistance of breast
      cancer cells to ADR. In addition, the loss of miRNA-200c correlated with
      decreased levels of E-cadherin and PTEN, and increased levels of ZEB1 and phospho
      Akt (p-Akt) in ADR-resistant breast cancer cells (MCF-7/ADR cells). More
      importantly, we demonstrated that the gain of miRNA-200c results in an increased
      sensitivity of cells to ADR, downregulation of ZEB1, upregulation of E-cadherin
      and PTEN, and inactivation of Akt signaling. Following the co-transfection of E
      cadherin siRNA, the miRNA-200c-mediated regulation of Akt signaling and PTEN was
      inhibited. Results of the present study also demonstrated that Akt signaling is
      involved in the ADR resistance of breast cancer cells since LY294002, an
      inhibitor of Akt signaling, partially restored the sensitivity of MCF-7/ADR cells
      to ADR. In conclusion, miRNA-200c inhibited Akt signaling through its effects on
      E-cadherin and PTEN, resulting in the inhibition of ADR resistance in breast
      cancer cells.

PMID- 23546451
TI  - Tonometric devices for central aortic systolic pressure measurements in patients
      with type 1 diabetes: comparison of the BPro and SphygmoCor devices.
AB  - OBJECTIVE: Central blood pressure may be a better risk marker than brachial blood
      pressure and can be measured noninvasively by tonometric devices. We investigate
      whether tonometric measurements are feasible in patients with diabetes and
      whether the degree of albuminuria or increased arterial stiffness affects
      measurements. PATIENTS AND METHODS: In 676 patients with type 1 diabetes,
      comparison of central aortic systolic pressure (CASP) measurements by the BPro
      and the SphygmoCor devices were made. The BPro device can obtain both office and
      24-h measurements, whereas the SphygmoCor device is an accepted device for CASP
      measurements. RESULTS: Measurements of CASP with both BPro and SphygmoCor were
      available in 598 (88.5%) patients (mean age 54 years; mean diabetes duration 33
      years; 45.2% women), and mean+/-SD of CASP was 122+/-17 and 118+/-17 mmHg,
      respectively (P<0.001). Linear and intraclass correlation coefficients between
      CASP estimated from BPro and SphygmoCor were r equal to 0.96 and 0.95 (P<0.001
      for both). The mean+/-SD difference between devices was 3.6+/-4.8 mmHg
      (P<0.001).Analyses according to the level of albuminuria or degree of arterial
      stiffness were confirmatory. CONCLUSION: In patients with type 1 diabetes,
      tonometric measurements of CASP with BPro and SphygmoCor showed strong
      correlations, although values differed by ~4 mmHg between devices. Level of CASP,
      arterial stiffness, and degree of albuminuria did not interfere with the
      agreement between devices.In addition, the BPro device can obtain 24-h
      measurements and may thus be useful to assess the diurnal patterns of CASP.

PMID- 23546452
TI  - The power of video recording: taking quality to the next level.

PMID- 23546453
TI  - A rapid rotation to an inverted seated posture inhibits muscle force, activation,
      heart rate and blood pressure.
AB  - Although previous studies have demonstrated neuromuscular and cardiovascular
      changes with slow inversion rates, emergencies, such as overturned vehicles and
      helicopters can occur rapidly. The purpose of this study was to investigate
      changes in neuromuscular and cardiovascular responses with rapid (1 s) and slower
      (3 s) transitions from upright to inverted seated positions. Twenty-two subjects
      performed separate and concurrent unilateral elbow flexion and leg extension
      maximal voluntary contractions (MVCs) for 6 s in an upright seated position and
      when inverted with 1 and 3 s rotations. Elbow flexion and leg extension force;
      biceps, triceps, quadriceps and hamstrings electromyographic (EMG) activity,
      heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP)
      were measured. Whether the elbow flexion or leg extension contractions occurred
      concurrently or individually, significant (p < 0.05) decreases in MVC force and
      EMG activity were found when inverted within 1 and 3 s rotations as compared to
      upright. Triceps and hamstrings EMG activity (p < 0.05) decreased when inverted
      within 1 s rotation as compared to upright. Following rotation, the maintenance
      of the inverted position (3-6 s timepoint) resulted in a significant (p < 0.05)
      increase in leg extension MVC as compared to the initial second of rotation to
      inversion. HR, SBP and DBP demonstrated (p < 0.001) decreases when inverted
      within 1 and 3 s rotations as compared to upright. In conclusion, this is the
      first study to show that irrespective of rotation speed, inversion inhibited
      neuromuscular and cardiovascular responses, similar to the more deliberate,
      slower rotation of previous inversion studies.

PMID- 23546454
TI  - Facile synthesis of a ruthenium assembly and its application for light-driven
      oxidation of alcohols in water.
AB  - A supramolecular assembly containing two light harvesting fragments
      [Ru(tpy)2](2+) and one catalytic unit [Ru(tpy)(bpy)Cl](+) was synthesized in a
      facile manner in 90% yield, and exhibited high photocatalytic product-selectivity
      compared with the corresponding bimolecular system in the light-driven oxidation
      of alcohols using [Co(NH3)5Cl]Cl2 as a sacrificial oxidant in water at room
      temperature.

PMID- 23546455
TI  - [Use of peripheral catheters: too much to learn].
AB  - Frequently incident complications due to the use of peripheral catheters are
      considered not relevant. However, recently multiple observational studies have
      demonstrated its role causing nosocomial bacteraemia. Guidelines about prevention
      of catheter-related infection are focused in central lines instead of peripheral
      ones. This approach causes an important lack of knowledge about the best manner
      to manipulate peripheral lines. Risk factors related to the development of a
      peripheral phlebitis, its clinical relevance and doubts related to prevention are
      presented and discussed in this article. The main objective is to alert about the
      importance of peripheral catheters in the prevention of nosocomial infection.

PMID- 23546456
TI  - [Malaria diagnosis and treatment: analysis of a cohort of hospitalised patients
      at a tertiary level hospital (1998-2010)].
AB  - INTRODUCTION: The increasing frequency of malaria infection in our area is due to
      the rise in international travel and immigration from endemic malaria areas. The
      aim of this study is to describe the chemoprophylaxis taken and treatment given
      as well as the clinical, epidemiological and microbiological characteristics for
      those patients admitted to our hospital with malaria. METHODS: A retrospective
      study of patients with malaria admitted to the Hospital Virgen de la Arrixaca,
      between January 1998 and December 2010, was carried out. RESULTS: During this
      period, fifty one cases of malaria were diagnosed. 78.3% of them were immigrants
      of whom 65% resided in Spain and had travelled to their country of origin for a
      short stay. Seventy four per cent acquired the infection in central and west
      Africa, and Plasmodium falciparum was responsible for the majority of the cases
      (88%). Only four patients had taken antimalarial chemoprophylaxis but none
      correctly. The most frequently treatment used was a combination of quinine and
      doxycicline (64.7%). Inappropriate anti-malarial treatment occurred in 9 patients
      (17.6%). At least one indicator of severe malaria was established in 23.5% of the
      cases; however, the clinical outcome was successful in every case and no patient
      died. CONCLUSIONS: Imported malaria is observed mostly among immigrants who
      travel to their countries of origin for a short stay and do not take anti
      malarial prophylaxis, increasing the risk of acquiring malaria. Inappropriate
      malarial treatment is relatively frequent in the case management of imported
      malaria.

PMID- 23546458
TI  - Morbidity and mortality associated with primary and catheter-related bloodstream
      infections in critically ill patients.
AB  - PURPOSE: To analyze the impact of primary and catheterrelated bloodstream
      infections (PBSI/CRBSI) on morbidity and mortality. METHODS: A matched case
      control study (1:4) was carried out on a Spanish epidemiological database of
      critically ill patients (ENVIN-HELICS). To determine the risk of death in
      patients with PBSI/CRBSI a matched Cox proportional hazard regression analysis
      was performed. RESULTS: Out of the 74,585 registered patients, those with at
      least one episode of monomicrobial PBSI/CRBSI were selected and paired with
      patients without PBSI/CRBSI for demographic and diagnostic criteria and
      seriousness of their condition on admission to the Intensive Care Unit (ICU). for
      mortality analysis, 1,879 patients with PBSI/CRBSI were paired with 7,516
      controls. The crude death rate in the ICU was 28.1% among the cases and 18.7%
      among the controls. Attributable mortality 9.4% (HR:1.20; 95% confidence
      interval: 1.07-1.34; p<0.001). Risk of death varied according to the source of
      infection, aetiology, moment of onset of bloodstream infection and severity on
      admission to the ICU. The median stay in the ICU of patients who survived
      PBSI/CRBSI was 13 days longer than the controls, also varying according to
      aetiology, moment of onset of bloodstream infection and severity on admission.
      CONCLUSIONS: Acquisition of PBSI/CRBSI in critically ill patients significantly
      increases mortality and length of ICU stay, which justifies prevention efforts.

PMID- 23546460
TI  - Invasion of solid culture media: a widespread phenotypic feature of clinical
      bacterial isolates.
AB  - OBJECTIVES: The in-depth growth in solid culture media is a common feature in
      filamentous fungi and yeasts. However, there are very few bacterial species in
      which this phenomenon has been documented. The aim of this work was to assess the
      agar invasiveness of a wide range of Gram-positive and Gram-negative bacterial
      species of clinical interest. MATERIAL AND METHODS: Three different clinical
      isolates for each of eleven bacterial species were plated onto Columbia blood
      agar and let grow up to 15 days. Isolated colonies were processed by histological
      methods, embedded in epoxy resin, and then, semithin sections were stained with
      toluidine blue and visualized by light microscopy. RESULTS: Growth within the
      agar was observed in at least one strain in 9 of the 11 studied species.
      Invasions of Gram-negative rods were small, not plentiful, and round or triangle
      shaped. In Gram-positive cocci, invasions were of big size, abundant and of
      variable shape (lentiform, globular, irregular, arrowhead) depending on the
      species. CONCLUSIONS: We propose that the growth within the agar can indicate a
      survival strategy common to many bacterial species, and so far, not previously
      reported. This strategy could be either a nutrient gradient tropism or the spread
      and colonization of new ecological niches, with potential implications in
      pathogeny.

PMID- 23546459
TI  - Pyelonephritis in pregnancy. How adequate is empirical treatment?
AB  - OBJECTIVE: To ascertain the adequacy of empirical antimicrobial treatment in
      pregnant women with acute pyelonephritis. MATERIAL AND METHODS: We have conducted
      a retrospective observational study of women admitted to the hospital with acute
      pyelonephritis between May 2004 and April 2011. Patients were included if the
      results of urine cultures and susceptibility testing to antibiotics were
      available. Epidemiological, clinical, therapeutical and outcome variables were
      collected from chart review. We considered inappropriate empirical antimicrobial
      treatment (IEAT) as the occurrence of microorganism that were not effectively
      treated at the time when the causative microorganism and its antibiotic
      susceptibility were known. RESULTS: Fifty women with appropriate microbiological
      data from a total of 93 cases of acute pyelonephritis were included in the study.
      The women's mean age was 26.4 years, and 58% were nulliparous. Pyelonephritis was
      developed in the 2nd and 3rd trimester in 88% of cases. Previous urinary tract
      infections were recorded in 34%. Escherichia coli was the most frequent
      microorganism (70%). The proportion of patients who received IEAT was 10%.
      Amoxicillin-clavulanate and cephalosporines were the most predominant antibiotics
      used, with a proportion of IEAT of 10.3% and 5.9%, respectively. CONCLUSIONS:
      Pregnant women with pyelonephritis received IEAT in a small but significant
      number of cases. Amoxicillin-clavulante and cephalosporines were adequate in most
      cases. More studies are needed to define the clinical impact of IEAT on
      prognosis.

PMID- 23546461
TI  - [Relevance of the detection of Streptococcus pneumoniae antigen in human urine in
      the diagnosis of lower respiratory tract infections].
AB  - BACKGROUND AND OBJECTIVE: Techniques membrane antigen immunochromatographic
      detecting in urine the pneumococcal polysaccharide C, have developed
      significantly, increasing requests for antigenuria to clinical microbiology
      laboratories. We evaluated the impact of the application of this test in the
      diagnosis of infections of lower respiratory tract. PATIENTS AND METHOD: Six
      hundred and sixteen determinations were performed by antigenuria BinaxNOW((r)) S.
      pneumoniae in as many patients over 14 years admitted to the Hospital
      Universitario Virgen de las Nieves (Granada) between November 2010 and March
      2011. RESULTS: In 91.1% of patients who were determined antigenuria the presence
      of respiratory symptoms justified the request. Only 8.4% of 616 antigenurias
      performed were positive. S. pneumoniae was isolated from the respiratory sample
      culture in 8 of these 52 patients. In 29.8% of patients the diagnosis of lower
      respiratory tract infection was based on clinical, radiological and/or
      analytical, as antigenurias were negative and did not involve any other
      additional microbiological test. CONCLUSIONS: We believe that this technique
      should be used in a complementary manner, and never to the detriment of other
      microbiological tests, especially in hospitalized patients.

PMID- 23546463
TI  - Detection and genotyping of human respiratory viruses in clinical specimens from
      children with acute respiratory tract infections.
AB  - Respiratory virus infections are a major health concern and represent the primary
      cause of testing consultation and hospitalization for young children. The
      application of nucleic acid amplification technology, particularly multiplex PCR
      coupled with fluidic or fixed microarrays, provides an important new approach for
      the detection of multiple respiratory viruses in a single test. The aim of this
      study was to analyze respiratory samples from children with acute respiratory
      tract infection (ARTI) using a commercial array-based method (CLART((r))
      PneumoVir Genomica, Coslada, Spain). These tests were used to identify viruses in
      281 nasopharyngeal samples obtained from children affected by ARTI. Samples were
      obtained form October 2008 to April 2009. Viruses were identified in 80% of the
      studied ARTI providing useful information on clinical features and epidemiology
      of specific agents affecting children in cold months. Multiple viral infections
      were found in 33.45% of the specimens.

PMID- 23546462
TI  - [Increasing prevalence of fosfomycin resistance in extended-spectrum-beta
      lactamase-producing Escherichia coli urinary isolates (2005-2009-2011)].
AB  - INTRODUCTION: Escherichia coli is the most important uropathogen. The appearance
      of extended- spectrum beta-lactamase (ESBL)-producing E.coli in urinary tract
      infections (UTI) constitutes an important therapeutic challenge that requires the
      study of its evolution throughout time in order to establish a suitable empirical
      treatment. Our aim was to determine the prevalence of ESBL-producing E. coli
      urinary isolates in 2005, 2009 and 2011. We also determined the antimicrobial
      coresistance to several agents, including fosfomycin. METHODS: We analyzed 5053,
      6324 and 6644 E. coli isolates obtained from urine cultures in 2005, 2009 and
      2011 respectively. Duplicate isolates were excluded. Antimicrobial susceptibility
      was determined by the Wider microdilution system (Soria Melguizo S.A.) and the
      phenotypic pattern of resistance that indicated a BLEE-producing E.coli was
      selected (CLSI 2009). RESULTS: 3.9% of strains (198) were ESBL producers in 2005,
      7.3% (463) in 2009 and 8.7% (584) in 2011. Resistance to carbapenems was detected
      in 2009, they inhibited more than the 95% of strains in 2011. Among the non-beta
      lactams, colistin was the most active antibiotic followed by nitrofurantoin.
      Ciprofloxacin and sulfamethoxazole-trimethoprim were not effective with 80% and
      60% resistant isolates, respectively. An increasing resistance trend, from 0% to
      9.3% in 2009 and 14.4% in 2011 was observed for fosfomycin. CONCLUSIONS: From
      2005 our institution had an increasing prevalence of ESBL-producing E. coli
      rising to 8.7% in 2011. Carbapenems are still the most active agents. The
      increase of resistance was significant for fosfomycin.

PMID- 23546457
TI  - [Physicians with access to point-of-care tests significantly reduce the
      antibiotic prescription for common cold].
AB  - OBJECTIVE: This study was aimed at evaluating the effect of two levels of
      intervention on the antibiotic prescribing in patients with common cold. METHODS:
      Before and after audit-based study carried out in primary healthcare centres in
      Spain. General practitioners registered all the episodes of common cold during 15
      working days in January and February in 2008 (preintervention). Two types of
      intervention were considered: full intervention, consisting in individual
      feedback based on results from the first registry, courses in rational antibiotic
      prescribing, guidelines, patient information leaflets, workshops on rapid tests 
      rapid antigen detection and C-reactive protein tests- and provision of these
      tests in the surgeries; and partial intervention, consisting of all the above
      intervention except for the workshop and they did not have access to rapid tests.
      The same registry was repeated in 2009 (postintervention). In addition, new
      physicians filled out only the registry in 2009 (control group). RESULTS: 210
      physicians underwent the full intervention, 71 the partial intervention and 59
      were assigned to the control group. The 340 doctors prescribed antibiotics in 274
      episodes of a total of 12,373 cases registered (2.2%).The greatest percentage of
      antibiotic prescription was found in the control group (4.6%). The partial
      intervention increased the antibiotic prescription percentage from 1.1% to 2.7%
      while only doctors who underwent the complete intervention lead to a significant
      reduction of antibiotics prescribed, from 2.9% before to 0.7% after the
      intervention (p<0.001). CONCLUSION: Only physicians with access to rapid tests
      significantly reduced antibiotic prescription in patients with common cold.

PMID- 23546464
TI  - [Candida sp endocarditis. Experience in a third-level hospital and review of the
      literature].
AB  - Despite the relative high frequency of Candida bloodstream infection, Candida
      endocarditis is a rare entity. We report five cases of Candida endocarditis
      admitted to our hospital in the period between 2005 and 2011. Two cases were
      caused by C. albicans, two cases were caused by C. parapsilosis and in the last
      one, we didn't identify the species of Candida. All but one had clear risk
      factors for candidemia. Treatment consisted of amphotericin B with / without
      flucytosine in four patients, and they all underwent surgery for valve
      replacement and / or removal of intravascular devices. Overall mortality was 60%
      (40% of mortality was directly related to endocarditis). All patients who
      survived were given suppressive therapy with fluconazole for a minimum of two
      years.After stopping fluconazole there was a case of recurrence.

PMID- 23546465
TI  - Use of tigecycline in critically ill patients with serious nosocomial intra
      abdominal infections.
AB  - Intra-abdominal infection (IAI) is a frequent complication found in surgical
      intensive care unit (SICU) and continues to be associated with considerable
      mortality. Tigecycline, the first-in-class glycylcycline has demonstrated a broad
      spectrum of activity against a wide range of bacteria commonly found in IAI. This
      observational retrospective study aimed to describe the experience with
      tigecycline for serious nosocomial IAI in the SICU. Data were collected from 23
      consecutive patients admitted to SICU with serious nococomial IAI who had
      received empirical treatment with tigecycline. In all cases, IAI was diagnosed
      via emergency surgery. Severe sepsis was found in 56.5% and 43.5% developed
      septic shock. Oncological disease was the most common comorbidity (60%). The mean
      Simplified Acute Physiology Score (SAPS) III within 24 hours from IAI diagnosis
      was 57.5+/-14.7, and 87% showed a McCabe score >1 (2 or 3). Escherichia coli was
      the most common pathogen (43.5%), followed by Bacteroides spp. and Streptococcus
      spp. (30.4%, respectively). All but one patient received tigecycline in
      combination (95.7%), particularly with fluconazole (52.2%), followed by
      piperacillin-tazobactam (43.5%). Empirical antibiotic therapy was considered
      adequate in 95%. The mean duration of treatment was 8.5+/-4.5 days. A favorable
      response was achieved in 78%. Failure of the antibiotic therapy was not observed
      in any patient. None of the patients discontinued tigecycline due to adverse
      reactions. SICU mortality was 13%, with no deaths attributable to tigecycline.
      These findings suggest that tigecycline combination therapy is an effective and
      well tolerated empirical treatment of serious nosocomial IAI in the SICU.

PMID- 23546466
TI  - Treatment of invasive fungal infections in high risk hematological patients. The
      outcome with liposomal amphotericin B is not negatively affected by prior
      administration of mold-active azoles.
AB  - There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given
      sequentially after mold-active azoles due to a possible antagonism in their
      antifungal mechanism. To investigate this possible effect in the clinic, we
      retrospectively studied 182 high risk hematologic patients with invasive fungal
      infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had
      possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC
      classification. Most had suspected or proven invasive aspergillosis. We compared
      patients with prior exposure to mold-active azoles (n=100) to those having not
      (n=82). The group with prior mold-active azoles included more patients with poor
      risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged
      neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or
      partial response, was achieved in 75% and 74.4% of patients in the whole cohort,
      and in 66% and 74.4% of patients with probable or proven IFI in the two groups.
      None of these differences were significant. Multivariate analysis showed that
      refractory baseline disease and renal dysfunction were adverse factors for
      response in the IFI (p<0.05). Survival was poorer for patients with prior broad
      spectrum azoles (p<0.05), and for those who did not recover from neutropenia
      (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal
      infection with L-AmB is not likely to be affected by prior exposure to mold
      active azoles prophylaxis, but survival largely depends on host and disease
      factors.

PMID- 23546467
TI  - [Serologic diagnosis of an outbreak of Mycoplasma pneumoniae pneumonia in a city
      of Santa Cruz de Tenerife].

PMID- 23546468
TI  - [Diabetic leg ulcer colonized by Bordetella trematum].

PMID- 23546469
TI  - [Identification of Mycobacteria in clinical specimens. Two cases].

PMID- 23546470
TI  - [Rapid identification of gram-positive cocci in blood cultures by latex
      agglutination techniques].

PMID- 23546471
TI  - [Acute meningitis by Streptococcus agalactiae in a immunocompetent male].

PMID- 23546472
TI  - Extent of late gadolinium enhancement on cardiovascular magnetic resonance
      imaging and its relation to left ventricular longitudinal functional reserve
      during exercise in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: The aim of this study was to investigate whether the extent of late
      gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging
      reflecting myocardial fibrosis correlates with left ventricular (LV) longitudinal
      function during exercise in hypertrophic cardiomyopathy (HCM). METHODS AND
      RESULTS: Mitral annular velocities (E' and S') were measured on echocardiography
      at rest and during graded bicycle exercise (25 W, 3-min increments) in 46 HCM
      patients (mean age, 53 years; 32 men). LV longitudinal diastolic and systolic
      functional reserve indices were calculated as DeltaE'*E'base and DeltaS'*S'base,
      where DeltaE' and DeltaS' are the changes in E' and S' from baseline to 50 W of
      exercise, respectively. The patients were divided into 2 groups according to the
      extent of LGE (as "percentage of LV mass containing LGE": %LV with LGE; range, 0
      37%; median, 6%): group 1 (n=23), %LV with LGE <6%, and group 2, %LV with LGE
      >=6%. Baseline echocardiographic parameters were similar between the 2 groups,
      but changes in E' and S' during exercise were smaller in group 2 (DeltaE': 2.8+/
      1.8 cm/s vs.1.5+/-1.0 cm/s, P=0.007; DeltaS': 2.2+/-1.2 cm/s vs. 0.9+/-0.8 cm/s,
      P<0.0001). LV functional reserve indices were also significantly lower in group 2
      (DeltaE'*E'(base): 12.8+/-7.7 vs. 5.5+/-3.4, P=0.001; DeltaS'*S'(base): 12.6+/
      7.4 vs. 4.7+/-4.5, P<0.0001). CONCLUSIONS: LV longitudinal function during
      exercise is influenced by the extent of LGE in HCM. Myocardial fibrosis may
      represent a pathologic substrate that determines LV functional reserve in
      patients with HCM.

PMID- 23546473
TI  - Long-term benefits following catheter ablation of atrial fibrillation.
AB  - Catheter ablation has acquired a prominent role in the management of symptomatic
      atrial fibrillation (AF). Attempting to accurately assess the benefit of ablation
      can be quite challenging and is influenced by many variables, including the type
      of AF, procedural technique, operator experience, and duration and method of
      follow-up. Equally elusive is the proper definition of a successful ablation
      outcome. Should a "successful" ablation necessitate complete resolution of AF and
      AF symptoms documented by long-term monitoring, or does a more clinical approach
      evaluating for symptomatic improvement constitute a favorable outcome?
      Furthermore, at what point following an ablation should a recurrence be an
      acceptable, if not an expected, occurrence and should a significant decrease in
      AF burden warrant consideration as success? Our goal here will be to explore the
      current data evaluating outcomes for ablation of AF. We will examine
      electrophysiologic and other clinical endpoints, and hope to provide long-term
      expectations following ablation of paroxysmal and persistent AF.  

PMID- 23546474
TI  - Variation in the incidence and timing of acute lung injury: the role of race.

PMID- 23546475
TI  - Joining the crowd: cystic fibrosis and cardiovascular disease risk factors.

PMID- 23546476
TI  - Systemic treatment of advanced lung carcinoid tumors: show me the data!

PMID- 23546478
TI  - Point: are >50 supervised procedures required to develop competency in performing
      endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal
      staging? Yes.

PMID- 23546479
TI  - Counterpoint: are >50 supervised procedures required to develop competency in
      performing endobronchial ultrasound-guided transbronchial needle aspiration for
      lung cancer staging? No.

PMID- 23546482
TI  - Protein misfolding and endoplasmic reticulum stress in chronic lung disease.
AB  - The pathogenesis of chronic lung disorders is poorly understood but is often
      thought to arise because of repeated injuries derived from exposure to exogenous
      or endogenous stress factors. Protein-misfolding events have been observed in a
      variety of genetic and nongenetic chronic lung disorders and may contribute to
      both the initiation and the progression of lung disease through endoplasmic
      reticulum (ER) stress and activation of the unfolded protein response (UPR).
      Evidence indicates that exposure to common lung irritants such as cigarette
      smoke, environmental pollutants, and infectious viral or bacterial agents can
      induce ER stress and protein misfolding. Although the UPR is thought to be a
      molecular mechanism involved in the repair and restoration of protein homeostasis
      or "proteostasis," prolonged activation of the UPR may lead to compromised
      cellular functions, cellular transformation, or cell death. Here, we review
      literature that associates protein-misfolding events with ER stress and UPR
      activation and discuss how this basic molecular repair mechanism may contribute
      to the initiation and progression of various genetic and nongenetic chronic lung
      diseases.

PMID- 23546483
TI  - Moving toward a more ideal anticoagulant: the oral direct thrombin and factor Xa
      inhibitors.
AB  - Thromboembolic diseases are common. Heparins and the vitamin K antagonists have
      been the mainstay of therapy for > 60 years, but both classes of agents have
      limitations. The "ideal" anticoagulant should be as effective and safe as heparin
      and vitamin K antagonists but should also be available in both a parenteral and
      an oral formulation, have predictable pharmacokinetics, and lack significant
      toxicities unrelated to the anticoagulant activity. Moreover, it should target a
      specific coagulation factor and have an antidote that leads to rapid reversal.
      There are now agents that fulfill some of these criteria. Here we review the
      pharmacology and effectiveness of the oral activated factor X inhibitors
      rivaroxaban and apixaban and the oral direct thrombin inhibitor dabigatran. These
      agents have undergone extensive phase 3 testing and are currently approved for
      various indications in the United States, Canada, or Europe. Rivaroxaban is
      approved in the United States for VTE prevention after major orthopedic surgery
      and for stroke prevention in atrial fibrillation and is approved in Europe and
      Canada for secondary prevention of VTE. Apixaban is currently under review by the
      US Food and Drug Administration for stroke prevention and is approved in Europe
      for VTE prevention following major orthopedic surgery. Dabigatran is approved in
      the United States for stroke prevention in nonvalvular atrial fibrillation and is
      being reviewed for secondary prevention of VTE.

PMID- 23546484
TI  - Lung cancer in China: challenges and interventions.
AB  - In 2008, lung cancer replaced liver cancer as the number one cause of death among
      people with malignant tumors in China. The registered lung cancer mortality rate
      increased by 464.84% in the past 3 decades, which imposes an enormous burden on
      patients, health-care professionals, and society. We performed a systematic
      review of the published data on lung cancer in China between 1990 and 2011 to
      analyze the incidence and mortality rates, economic burden, and risk factors of
      cancer and the effectiveness of interventions. Lung cancer incidence varies
      within China. People in eastern China, especially women, likely have a higher
      risk of developing lung cancer than those in western China. The crude mortality
      rates from lung cancer in 2008 were 47.51 per 100,000 men and 22.69 per 100,000
      women. The crude mortality rate was highest in Shanghai (76.49 per 100,000 men
      and 35.82 per 100,000 women) and lowest in Tibet (25.14 per 100,000 men) and
      Ningxia (12.09 per 100,000 women). Smoking and environmental pollution are major
      risk factors for lung cancer in China. Continuous efforts should be concentrated
      on education of the general public regarding lung cancer to increase prevention
      and early detection. Specific interventions need to be implemented to reduce
      smoking rates and environmental risk factors. Standardized treatment protocols
      should be adapted in China.

PMID- 23546486
TI  - Making paracentesis safer: a proposal for the use of bedside abdominal and
      vascular ultrasonography to prevent a fatal complication.
AB  - Paracentesis has been considered a relatively safe procedure; however,
      hemorrhagic complications do occur and can be fatal, especially in the context of
      coagulopathy. We describe the case of a 47-year-old man with coagulopathy
      secondary to end-stage liver disease, whose hospital course was complicated by
      paracentesis-related hemoperitoneum leading to abdominal compartment syndrome.
      Emergent laparotomy revealed left inferior epigastric artery laceration caused by
      paracentesis. Despite operative control of bleeding, postoperatively, the patient
      developed severe metabolic acidosis, disseminated intravascular coagulation, and
      ultimately died from complications of hemorrhagic shock. Understanding key
      anatomic structures is essential for patient safety in the setting of
      paracentesis. While recognizing the lack of clinical studies demonstrating the
      effectiveness of ultrasonography use in paracentesis, we discuss the benefit of
      bedside abdominal ultrasonography to locate ascites and avoid intraabdominal
      structures, as well as vascular ultrasonography, during needle insertion to avoid
      abdominal wall vessels.

PMID- 23546485
TI  - Limitations of medical research and evidence at the patient-clinician encounter
      scale.
AB  - We explore some philosophical and scientific underpinnings of clinical research
      and evidence at the patient-clinician encounter scale. Insufficient evidence and
      a common failure to use replicable and sound research methods limit us. Both
      patients and health care may be, in part, complex nonlinear chaotic systems, and
      predicting their outcomes is a challenge. When trustworthy (credible) evidence is
      lacking, making correct clinical choices is often a low-probability exercise.
      Thus, human (clinician) error and consequent injury to patients appear
      inevitable. Individual clinician decision-makers operate under the philosophical
      influence of Adam Smith's "invisible hand" with resulting optimism that they will
      eventually make the right choices and cause health benefits. The presumption of
      an effective "invisible hand" operating in health-care delivery has supported a
      model in which individual clinicians struggle to practice medicine, as they see
      fit based on their own intuitions and preferences (and biases) despite the
      obvious complexity, errors, noise, and lack of evidence pervading the system. Not
      surprisingly, the "invisible hand" does not appear to produce the desired
      community health benefits. Obtaining a benefit at the patient-clinician encounter
      scale requires human (clinician) behavior modification. We believe that serious
      rethinking and restructuring of the clinical research and care delivery systems
      is necessary to assure the profession and the public that we continue to do more
      good than harm. We need to evaluate whether, and how, detailed decision-support
      tools may enable reproducible clinician behavior and beneficial use of evidence.

PMID- 23546487
TI  - Preparing for accountable care organizations: a physician primer.
AB  - The concept of the accountable care organization (ACO) offers the opportunity to
      better integrate the health system into a value proposition aligned toward
      improved care, more efficient delivery, and higher patient satisfaction. As a
      significant component of health reform, the ACO has many implications for
      physicians. Physicians interested in joining ACOs have a variety of options,
      including forming their own, integrating (virtual or otherwise) with larger
      health systems, or joining multiple, existing ACOs. To succeed, fundamental
      changes away from the past fee-for-service model will be necessary. Clinical and
      financial data will become of paramount importance. The data will need to be more
      accessible, more accurate, and more appropriately used to align with the greater
      ACO value proposition. Physicians will also need to embrace the "era of
      persuasion" with its underlying assumption that engaging patients and other
      physicians are as necessary as a proper diagnosis and treatment plan. As there is
      a wide array of options in the marketplace, providers must have a clear
      understanding of patient attribution, financial incentives, and quality metrics
      within any ACO agreement. Finally, the health-care system must acknowledge the
      difficulties associated with the pace of change itself and invest in resources to
      aid in the adaptive reserve of all components of the health-care system.

PMID- 23546488
TI  - Fentanyl-induced chest wall rigidity.
AB  - Fentanyl and other opiates used in procedural sedation and analgesia are
      associated with several well-known complications. We report the case of a man who
      developed the uncommon complication of chest wall rigidity and ineffective
      spontaneous ventilation following the administration of fentanyl during an
      elective bronchoscopy. His ventilation was assisted and the condition was
      reversed with naloxone. Although this complication is better described in
      pediatric patients and with anesthetic doses, chest wall rigidity can occur with
      analgesic doses of fentanyl and related compounds. Management includes
      ventilatory support and reversal with either naloxone or a short-acting
      neuromuscular blocking agent. This reaction does not appear to be a
      contraindication to future use of fentanyl or related compounds. Chest wall
      rigidity causing respiratory compromise should be readily recognized and treated
      by bronchoscopists.

PMID- 23546489
TI  - Successful treatment of severe amiodarone pulmonary toxicity with polymyxin B
      immobilized fiber column direct hemoperfusion.
AB  - Amiodarone pulmonary toxicity (APT) is the most serious side effect of
      amiodarone. Although severe APT, such as ARDS, is rare, mortality of severe APT
      is high. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is a
      medical device that reduces blood endotoxin levels in sepsis. Recent reports have
      shown that PMX-DHP improves oxygenation in patients with acute exacerbation of
      idiopathic pulmonary fibrosis and drug-induced severe interstitial pneumonia.
      Here, we present a case study of a patient with severe APT treated with PMX-DHP
      with complete recovery. The patient rapidly developed respiratory failure and
      required mechanical ventilation. Despite corticosteroid pulse therapy, no
      clinical improvement was noted. PMX-DHP was then started, and severe respiratory
      failure improved with reduction of serum levels of amiodarone and its metabolite
      monodesethylamiodarone. The patient was weaned from mechanical ventilation and
      has done well without recurrence. To our knowledge, this is the first reported
      case of PMX-DHP therapy for severe APT. We speculate that PMX-DHP could be a new
      treatment strategy for severe APT.

PMID- 23546490
TI  - Balancing the risks and benefits of oxygen therapy in critically III adults.
AB  - Oxygen therapy is an integral part of the treatment of critically ill patients.
      Maintenance of adequate oxygen delivery to vital organs often requires the
      administration of supplemental oxygen, sometimes at high concentrations. Although
      oxygen therapy is lifesaving, it may be associated with deleterious effects when
      administered for prolonged periods at high concentrations. Here, we review the
      recent advances in our understanding of the molecular responses to hypoxia and
      high levels of oxygen and review the current guidelines for oxygen therapy in
      critically ill patients.

PMID- 23546491
TI  - A 59-year-old woman who is awake yet unresponsive and stuporous after liver
      transplantation.

PMID- 23546492
TI  - A 51-year-old man presenting with shock and lower-lobe consolidation with
      interlobar bulging fissure.

PMID- 23546493
TI  - A 46-year-old woman with atelectasis from an endobronchial tumor.

PMID- 23546494
TI  - Spontaneous pneumothorax in a 50-year-old man with diffuse pulmonary nodules.

PMID- 23546496
TI  - Neurally adjusted ventilatory assist vs pressure support ventilation during
      noninvasive mechanical ventilation: another physiologic evaluation to consider?

PMID- 23546497
TI  - Response to Dr Esquinas.

PMID- 23546498
TI  - Backup respiratory rate during noninvasive positive pressure ventilation in
      obesity hypoventilation syndrome: can this difficult puzzle be resolved?

PMID- 23546499
TI  - Response to Dr Esquinas.

PMID- 23546500
TI  - Telemedicine programs in ICUs are proven to drive hospitals' clinical, financial,
      and operational success.

PMID- 23546501
TI  - Response to Dr Gorman.

PMID- 23546502
TI  - Probiotics for prevention of ventilator-associated pneumonia.

PMID- 23546503
TI  - Response to Drs Siempos and Ntaidou.

PMID- 23546504
TI  - Obesity, dyslipidemia, and sleep disorders: complexity requires complementary
      analysis.

PMID- 23546505
TI  - Response to Mr Polesel and colleagues.

PMID- 23546506
TI  - Hypersensitivity pneumonitis due to metalworking fluid exposures.

PMID- 23546507
TI  - Response to Dr Barber and colleagues.

PMID- 23546508
TI  - American College of Chest Physicians guidelines for heparin-induced
      thrombocytopenia: a need for evidence-based assessment of the baseline risk of
      heparin-induced thrombocytopenia.

PMID- 23546509
TI  - Response to Dr Junqueira.

PMID- 23546510
TI  - Significance of lymphadenopathy in IgG4-related sclerosing disease and
      sarcoidosis.

PMID- 23546511
TI  - A 47-year-old man with dyspnea and hypotension.

PMID- 23546512
TI  - Posterior acetabular arc angle of the femoral head assesses instability of
      posterior fracture-dislocation of the hip.
AB  - PURPOSE: Unstable posterior fracture-dislocation of the hip is determined by the
      wall defect or acetabular fracture index. The unstable hip is a result of
      inadequate posterior acetabular coverage of the femoral head from the posterior
      acetabular wall fracture. In order to measure total posterior acetabular coverage
      of the femoral head and avoid using the contralateral acetabulum as a calculation
      reference, the posterior acetabular arc angle of the femoral head was measured to
      assess stability of posterior fracture-dislocation of the hip. METHODS: Using
      coronal computed tomography (CT) scan of the normal contralateral acetabulum at
      the level of the widest acetabular diameter and thinnest medial wall of 60
      acetabular fractures, posterior acetabular arc angles of the femoral head in
      intact, 20 % and 50 % defects of posterior acetabular walls were measured. The
      angles were measured from the acetabular centre to the thinnest medial wall and
      to the top, inner cortex of 80 % and 50 % posterior acetabular walls. RESULTS:
      Average intact, 80 % and 50 % posterior acetabular walls were 33.82 +/- 4.30,
      26.88 +/- 3.33 and 16.91 +/- 2.15 mm which corresponded to 92.25 +/- 11.34, 77.42
      +/- 10.04 and 50.63 +/- 6.58 degrees  of posterior acetabular arc angles of the
      femoral head. The intraclass correlation coefficient (ICC) of the measurements
      including correlation of conversion of posterior acetabular wall depths to
      posterior acetabular arc angles of the femoral head were more than 0.82 and 0.89.
      CONCLUSIONS: The measurement technique of posterior acetabular arc angle of the
      femoral head has strong reliability. Therefore, stable or unstable posterior
      fracture-dislocation of the hip can be determined in terms of more than 77
      degrees or less than 50 degrees of posterior acetabular arc angles of the femoral
      head instead of less than 20 % or more than 50 % posterior acetabular wall
      defect.

PMID- 23546513
TI  - Controlled release of human growth hormone fused with a human hybrid Fc fragment
      through a nanoporous polymer membrane.
AB  - Nanotechnology has been applied to the development of more effective and
      compatible drug delivery systems for therapeutic proteins. Human growth hormone
      (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human
      IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH
      hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared
      with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane
      with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of
      hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was
      found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B
      lymphocyte and to exhibit an almost identical circular dichroism spectrum to that
      of the original hGH-hyFc, suggesting that the released fusion protein should
      maintain the functional and structural integrity of hGH. Thus, the nanoporous
      release device could be a potential delivery system for the long-term controlled
      release of therapeutic proteins fused with the hybrid Fc fragment.

PMID- 23546514
TI  - Three-dimensional quantum photonic elements based on single nitrogen vacancy
      centres in laser-written microstructures.
AB  - To fully integrate quantum optical technology, active quantum systems must be
      combined with resonant microstructures and optical interconnects harvesting and
      routing photons in three diemsnsions (3D) on one chip. We fabricate such combined
      structures for the first time by using two-photon laser lithography and a
      photoresist containing nanodiamonds including nitrogen vacancy-centers. As an
      example for possible functionality, single-photon generation, collection, and
      transport is successfully accomplished. The single photons are efficiently
      collected via resonators and routed in 3D through waveguides, all on one optical
      chip. Our one-step fabrication scheme is easy to implement, scalable and
      flexible. Thus, other complex assemblies of 3D quantum optical structures are
      feasible as well.

PMID- 23546515
TI  - Potential implication of IL-24 in lymphangiogenesis of human breast cancer.
AB  - Lymphangiogenesis is involved in the dissemination of malignant cells from solid
      tumours to regional lymph nodes and possibly to various distant sites.
      Lymphangiogenesis is regulated by vascular endothelial growth factor (VEGF)-C and
      VEGF-D. Interleukin (IL)-24 is known as a cytokine with potent antitumour and
      tumour-suppressive activity which functions through its receptor (IL-22R).
      Expression of IL-24 has been shown to be reduced in breast cancer, and the
      reduced expression is associated with lymphatic metastases and a poor prognosis.
      However, the involvement of IL-24 in lymphangiogenesis during lymphatic
      metastasis remains unclear. The aim of the present study was to determine whether
      there is an association between IL-24, IL-22R and lymphangiogenic factors and
      markers in breast cancer. Analysis of IL-24, IL-22R and lymphangiogenic factors
      in malignant breast tissue samples (n=127) revealed a correlation between
      increased expression of lymphangiogenic markers (podoplanin, Prox-1 and LYVE-1)
      and reduced levels of IL-24 and IL-22R. Samples stained with a high degree of
      positivity for lymphangiogenic factors and markers whereas staining for IL-24 was
      weak. In vitro assays showed that the average perimeter length of microtubules
      formed by endothelial cells treated with IL-24 was significantly reduced compared
      to the control. The growth of endothelial cells was significantly reduced when
      exposed to a high concentration of IL-24 (250 ng/ml). Treatment of HECV cells
      with IL-24 resulted in significantly reduced expression of VEGF-C (P<0.05) and
      VEGF-D (P<0.001). In conclusion, reduced expression of IL-24 and IL-22R in breast
      cancer is correlated with increased expression of specific lymphangiogenic
      markers. IL-24 suppressed in vitro growth and microtubule formation of
      endothelial cells. IL-24 may downregulate the expression of lymphangiogenic
      markers and factors although further research is required. This suggests that IL
      24 plays a profound role in suppressing tumour lymphangiogenesis, thereby,
      reducing the likelihood of cancer metastasis via the lymphatic route.

PMID- 23546516
TI  - Diagnosis: CT colonography has finally arrived.

PMID- 23546517
TI  - Radiotherapy: Sparing early stage patients with Hodgkin lymphoma.

PMID- 23546518
TI  - Haematological cancer: Nilotinib reduces emergence of BCR-ABL mutations in CML.

PMID- 23546519
TI  - Haematological cancer: Lenalidomide improves response.

PMID- 23546520
TI  - Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen
      receptors.
AB  - Most B-cell malignancies express CD19, and a majority of patients with B-cell
      malignancies are not cured by current standard therapies. Chimeric antigen
      receptors (CARs) are fusion proteins consisting of antigen recognition moieties
      and T-cell activation domains. T cells can be genetically modified to express
      CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in
      clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was
      first reported in 2010 after a patient with advanced-stage lymphoma treated at
      the NCI experienced a partial remission of lymphoma and long-term eradication of
      normal B cells. Additional patients have subsequently obtained long-term
      remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR
      T cells. Long-term eradication of normal CD19(+) B cells from patients receiving
      infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific
      activity of these T cells. Some patients treated with anti-CD19 CAR T cells have
      experienced acute adverse effects, which were associated with increased levels of
      serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early
      stage of development, the potent antigen-specific activity observed in patients
      suggests that infusions of anti-CD19 CAR T cells might become a standard therapy
      for some B-cell malignancies.

PMID- 23546522
TI  - Singapore Pharmacogenomics Portal: a web resource for evaluating human genetic
      variations of genes responsible for drug responses.
AB  - The Singapore Pharmacogenomics Portal is the first genomics web platform that
      links public resources from PharmGKB and DrugBank with population genetics data
      from the International HapMap Project and the Singapore Genome Variation Project.
      The web portal provides the opportunity to survey genetic differences across
      populations for all autosomal genes in the genome, and serves as an integrated
      platform for linking these data with drugs and genetic variants that affect drug
      responses, adverse reactions, and dosage requirements. We envisage that the
      information provided by the portal will be useful to drug regulators and clinical
      researchers when evaluating the transferability of results from clinical trials
      conducted in one population to other populations for which no direct clinical
      testing has been conducted. The utility of this resource may extend to other
      countries in the region that also have significant populations of Chinese, Malay,
      or Indian ancestry.

PMID- 23546521
TI  - The future of epigenetic therapy in solid tumours--lessons from the past.
AB  - The promise of targeting epigenetic abnormalities for cancer therapy has not been
      realized for solid tumours, although increasing evidence is demonstrating its
      worth in haematological malignancies. In fact, true clinical efficacy in
      haematopoietic-related neoplasms has only become evident at low doses of
      epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA
      methyltransferases). Describing data from preclinical studies and early clinical
      trial results, we hypothesize that in using low-dose epigenetic-modulating
      agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic
      and off-target effect observed at high dose. We suggest that such optimization of
      drug dosing and scheduling of currently available agents could give these agents
      a prominent place in cancer management--when used alone or in combination with
      other therapies. If so, optimal use of these known agents might also pave the way
      for the introduction of other agents that target the epigenome.

PMID- 23546524
TI  - Insight into Sweet's syndrome and associated-malignancy: a review of the current
      literature.
AB  - Sweet's syndrome (acute febrile neutrophilic dermatosis) is an infrequent skin
      disease characterized by sudden onset of fever, leucocytosis and erythematous
      plaques or nodules infiltrated by neutrophils. There are three main clinical
      settings in which Sweet's syndrome has been described: classical or idiopathic
      Sweet's syndrome, malignancy-associated Sweet's syndrome and drug-induced Sweet's
      syndrome. Classical Sweet's is often preceded by an upper respiratory tract
      infection and may be associated with inflammatory bowel disease and pregnancy.
      Approximately 21% of patients have an associated malignancy, most commonly
      hematological disease. The syndrome may occur as a paraneoplastic accompaniment
      to established cancer or may be a first sign of malignancy or its recurrence. The
      incidence is said to be increasing in recent years due to the frequent use of
      growth factors in cancer patients. Several anticancer agents including all-trans
      retinoic acid proteosome inhibitors, hypomethylating agents, tyrosine kinase
      inhibitors and lenalidomide are potential harbingers of Sweet's syndrome.
      Unfortunately, little is known about the pathophysiology of Sweet's syndrome and
      there are no established guidelines for treatment of malignancy-associated
      Sweet's syndrome. Systemic corticosteroids are the mainstay of treatment. Sweet's
      syndrome caused by anticancer agents sometimes involves withdrawal or temporary
      discontinuation of anticancer agents, use of systemic corticosteroids and/or
      rechallenge with either with the same anticancer agents or different agents. This
      report provides insights into the pathophysiology, clinical presentation,
      diagnostic work, differential diagnosis and management of malignancy-associated
      Sweet's syndrome published in reported cases.

PMID- 23546523
TI  - Peripheral inflammation in neurodegeneration.
AB  - Neuroinflammation is now a well-characterised feature of neurodegenerative
      diseases. Immune dysfunction outside the central nervous system is also
      increasingly recognised as part of the diseases. Peripheral inflammation has
      emerged as a modulator of disease progression and neuropathology in several
      neurodegenerative diseases, making it targetable in new therapeutic approaches.
      In addition, the easy accessibility of blood immune cells and markers makes them
      ideal candidates for use as possible biomarkers and a potential model of central
      immune cells.

PMID- 23546525
TI  - Azidoacetylene--interpretation of gas phase infrared spectra based on high-level
      vibrational configuration interaction calculations.
AB  - Azidoacetylene is a highly explosive substance, which has been synthesized and
      characterized for the first time quite recently [Banert et al., Angew. Chem.,
      Int. Ed., 2012, 51, 7515]. As outlined in this work, the vibrational spectrum of
      azidoacetylene is dominated by strong couplings. For that reason, we have studied
      the vibrational spectrum of the title compound by gas phase measurements and high
      level vibrational structure calculations beyond the harmonic approximation. Based
      on the interplay of theory and experiment, we were able to identify all
      fundamentals, strong Fermi resonances and intense overtones, which contribute to
      the spectrum.

PMID- 23546526
TI  - Nocturnal cramps: a nerve problem.

PMID- 23546527
TI  - Alzheimer's phenotypes induced by overexpression of human presenilin 2 mutant
      proteins stimulate significant changes in key factors of glucose metabolism.
AB  - Alzheimer's disease (AD) is closely associated with significant defects in
      glucose metabolism. To investigate whether AD pathology induced by overexpression
      of human mutant presenilin 2 (PS2) protein induces changes in glucose metabolism,
      glucose-related factors were analyzed in the brain of 12-month-old neuron
      specific enolase (NSE)/hPS2m transgenic (Tg) mice. NSE/hPS2m Tg mice used in this
      study showed AD-like phenotypes such as the accumulation of Abeta-42, the
      increase of gamma-secretase activity and Tau hyperphosphorylation. A significant
      increase of glucose levels accompanied by a decrease of insulin levels was
      detected in NSE/hPS2m Tg mice, while the expression levels of insulin receptors
      were significantly decreased in NSE/hPS2m Tg mice compared to the non-Tg
      littermates without affecting the insulin-like growth factor (IGF) receptor.
      Moreover, the levels of AKT phosphorylation involved in the downregulation of the
      insulin receptor signaling pathway were reduced in the brain of NSE/hPS2m Tg mice
      compared with non-Tg littermate, although the levels of glycogen synthase kinase
      3 (GSK-3) beta phosphorylation were higher in the NSE/hPS2m Tg mice compared to
      non-Tg littermates. Furthermore, the levels of the expression of Glut-1 and -3
      were significantly reduced in the NSE/hPS2m Tg mice compared to those of control
      mice without affecting the Glut-4 protein expression between the two groups of
      mice. In particular, the levels of the Abeta-42 peptide in the brain of insulin
      treated NSE/hPS2m Tg mice were found to be slightly lower compared with those of
      the Abeta-42 peptide in the non-treated PS2 transgenic mice. Thus, the data
      presented in this study provide strong evidence that key factors of glucose
      metabolism are closely associated with the AD pathology induced by the hPS2m
      protein, and that insulin can serve as a potential therapeutic for AD patients.

PMID- 23546529
TI  - Wide-complex tachycardia in a patient with coronary disease--quiz case.

PMID- 23546528
TI  - Genome-wide characterization of phenylalanine ammonia-lyase gene family in
      watermelon (Citrullus lanatus).
AB  - Phenylalanine ammonia-lyase (PAL), the first enzyme in the phenylpropanoid
      pathway, plays a critical role in plant growth, development, and adaptation. PAL
      enzymes are encoded by a gene family in plants. Here, we report a genome-wide
      search for PAL genes in watermelon. A total of 12 PAL genes, designated ClPAL1
      12, are identified . Nine are arranged in tandem in two duplication blocks
      located on chromosomes 4 and 7, and the other three ClPAL genes are distributed
      as single copies on chromosomes 2, 3, and 8. Both the cDNA and protein sequences
      of ClPALs share an overall high identity with each other. A phylogenetic analysis
      places 11 of the ClPALs into a separate cucurbit subclade, whereas ClPAL2, which
      belongs to neither monocots nor dicots, may serve as an ancestral PAL in plants.
      In the cucurbit subclade, seven ClPALs form homologous pairs with their
      counterparts from cucumber. Expression profiling reveals that 11 of the ClPAL
      genes are expressed and show preferential expression in the stems and male and
      female flowers. Six of the 12 ClPALs are moderately or strongly expressed in the
      fruits, particularly in the pulp, suggesting the potential roles of PAL in the
      development of fruit color and flavor. A promoter motif analysis of the ClPAL
      genes implies redundant but distinctive cis-regulatory structures for stress
      responsiveness. Finally, duplication events during the evolution and expansion of
      the ClPAL gene family are discussed, and the relationships between the ClPAL
      genes and their cucumber orthologs are estimated. 

PMID- 23546530
TI  - PEGylated hybrid ytterbia nanoparticles as high-performance diagnostic probes for
      in vivo magnetic resonance and X-ray computed tomography imaging with low
      systemic toxicity.
AB  - Novel nanoparticulate contrast agents with low systemic toxicity and inexpensive
      character have exhibited more advantages over routinely used small molecular
      contrast agents for the diagnosis and prognosis of disease. Herein, we designed
      and synthesized PEGylated hybrid ytterbia nanoparticles as high-performance
      nanoprobes for X-ray computed tomography (CT) imaging and magnetic resonance (MR)
      imaging both in vitro and in vivo. These well-defined nanoparticles were facile
      to prepare and cost-effective, meeting the criteria as a biomedical material.
      Compared with routinely used Iobitridol in clinic, our PEG-Yb2O3:Gd nanoparticles
      could provide much significantly enhanced contrast upon various clinical voltages
      ranging from 80 kVp to 140 kVp owing to the high atomic number and well
      positioned K-edge energy of ytterbium. By the doping of gadolinium, our
      nanoparticulate contrast agent could perform perfect MR imaging simultaneously,
      revealing similar organ enrichment and bio-distribution with the CT imaging
      results. The super improvement in imaging efficiency was mainly attributed to the
      high content of Yb and Gd in a single nanoparticle, thus making these
      nanoparticles suitable for dual-modal diagnostic imaging with a low single
      injection dose. In addition, detailed toxicological study in vitro and in vivo
      indicated that uniformly sized PEG-Yb2O3:Gd nanoparticles possessed excellent
      biocompatibility and revealed overall safety.

PMID- 23546532
TI  - Optically programmable excitonic traps.
AB  - With atomic systems, optically programmed trapping potentials have led to
      remarkable progress in quantum optics and quantum information science.
      Programmable trapping potentials could have a similar impact on studies of
      semiconductor quasi-particles, particularly excitons. However, engineering such
      potentials inside a semiconductor heterostructure remains an outstanding
      challenge and optical techniques have not yet achieved a high degree of control.
      Here, we synthesize optically programmable trapping potentials for indirect
      excitons of bilayer heterostructures. Our approach relies on the injection and
      spatial patterning of charges trapped in a field-effect device. We thereby
      imprint in-situ and on-demand electrostatic traps into which we optically inject
      cold and dense ensembles of excitons. This technique creates new opportunities to
      improve state-of-the-art technologies for the study of collective quantum
      behavior of excitons and also for the functionalisation of emerging exciton-based
      opto-electronic circuits.

PMID- 23546531
TI  - Adequacy of lymph node retrieval for ampullary cancer and its association with
      improved staging and survival.
AB  - BACKGROUND: The aim of the present study was to determine the optimal number of
      lymph nodes (LN) examined to stage pN0 tumors after surgery for ampulla of Vater
      carcinoma (AVC). METHODS: We reviewed retrospectively 127 patients with AVC who
      underwent pancreaticoduodenectomy (1990-2008). Univariate and multivariate
      analysis was performed. RESULTS: Fifty-nine patients (46.5 %) were pN0, whereas
      68 patients (53.5 %) were pN1. The 5-year disease-specific survival (DSS) was
      worse for pN1 patients than for pN0 patients (46 vs. 77 %; P < 0.0001). In the
      pN0 cohort, the optimal cut-off number of LN analyzed was found to be 12. The 5
      year DSS for patients with <= 12 LN was 50 %, compared with 89 % in those with
      >12 LN (P = 0.001). By multivariate analysis, a LN count >12 was the only
      independent predictor associated with improved survival (HR 0.16, P = 0.003)
      among pN0 patients. Among pN1 patients, a LN count >12 was associated with a
      significantly better 5-year DSS (59 vs. 22 %; P = 0.027). Patients with a lymph
      node ratio (LNR) >0.20 had a 5-year DSS of 24 %, compared with 58 % in those with
      0 < LNR <= 0.20 (P = 0.038). CONCLUSIONS: Removal of more than 12 LN for
      examination is associated with improved survival rate after surgery for AVC in
      both pN0 and pN1 patients.

PMID- 23546533
TI  - Discoidin domain receptor 2 regulates the adhesion of fibroblasts to 3D collagen
      matrices.
AB  - The collagen matrix constitutes the primary extracellular matrix (ECM) portion of
      mammalian connective tissues in which the interaction of the cell and the
      surrounding collagen fibers has a significant impact on cell and tissue
      physiology, including morphogenesis, development and motility. Discoidin domain
      receptors (DDR1 and DDR2) have been identified as the receptor tyrosine kinases
      that are activated upon collagen binding. However, there is a lack of evidence
      regarding the effect of DDRs on the mechanical interaction between fibroblasts
      and ECM. In this study, we demonstrated that one of the major phosphotyrosine
      proteins in human fibroblasts during 3D collagen matrix polymerization is DDR2.
      Treatment of fibroblasts in 3D collagen matrices with platelet-derived growth
      factor (PDFG) has been shown to increase DDR2 phosphorylation. Silencing of DDR2
      with siRNA in fibroblasts significantly reduced the number of dendritic
      extensions regardless of whether cells were cultured in the collagen or
      fibronectin 3D matrices. Decreasing dendritic extensions in DDR2-silenced cells
      has also been shown to decrease the ability of fibroblast entanglement to
      collagen fibrils in 3D collagen matrices. Finally, we also showed that the
      silencing of DDR2 decreased the cell migration in 3D nested collagen matrices but
      had no effect on 3D floating matrix contraction. Collectively, these results
      suggest that DDR2 functioning is required for the membrane dynamics to control
      the mechanical attachment of fibroblasts to the 3D collagen matrices in an
      integrin-independent manner.

PMID- 23546534
TI  - Seasonal respiratory syncytial virus prophylaxis based on predetermined dates
      versus regional surveillance data.
AB  - BACKGROUND: In Ontario, Canada, the respiratory syncytial virus (RSV) prophylaxis
      period onset is defined by a fixed-date set provincially each year and offset by
      local hospital RSV admission activity. Inaccurate timing can result in inadequate
      or more costly prophylaxis. METHODS: RSV positivity (2002/03 to 2010/11) was
      obtained from a local database. RSV activity was described: season start/end
      dates, duration and optimum number of palivizumab doses required compared with
      doses administered for the final 4 RSV seasons (2007 to 2011). Three prophylaxis
      period-setting methods were evaluated for seasons 2007/08 to 2010/11: 1) the
      provincial method currently in use, 2) a local fixed-date method based on
      laboratory data accrued from the previous 5 seasons and 3) an exploratory
      prospective method based on surveillance of laboratory data. These were compared
      with the observed RSV seasons. RESULTS: The local RSV pattern closely reflects
      provincial seasonality. The local median season duration was 125 days (range 90
      181). Median season onset and offset dates were December 19 and April 16,
      respectively. The prophylactic period definitions corresponded similarly, but the
      provincially set and local fixed-date methods provided longer immunity periods
      than required for the actual RSV season and involved the administration of more
      than 5 palivizumab doses compared with the prospective method. CONCLUSIONS: The
      provincial prophylactic period aligned with the local fixed-date and prospective
      methods. However, the adoption of any of the first 2 strategies merits close
      observation to minimize excess healthcare expenditure. The prospective
      surveillance of laboratory isolates should be further explored as a preferred
      option to better define prophylactic periods.

PMID- 23546535
TI  - Clostridium difficile infection in the hospitalized pediatric population:
      increasing trend in disease incidence.
AB  - To determine whether the incidence of Clostridium difficile infection continues
      to increase in hospitalized pediatric patients, we evaluated data from a United
      States national inpatient database. For the period of 2003 to 2009, we found an
      increasing trend in the incidence of C. difficile infection. These data suggest
      greater effort be given to prevent and treat this infection in children. 

PMID- 23546537
TI  - Longitudinal associations between caregiver burden and patient and spouse
      distress in couples coping with lung cancer.
AB  - PURPOSE: While spouses play a vital role in the care of cancer patients,
      caregiving exerts a physical and psychological toll. Caregiving burden may not
      only compromise spouses' quality of life but also the quality of care and support
      they are able to provide. Consequently, spousal caregiving burden may also
      negatively impact patients' psychological adjustment. However, the effect of
      caregiving burden on patients' psychological distress is unknown. Thus, this 6
      month longitudinal study examined the associations between caregiving burden and
      distress in both lung cancer patients and their spouses. METHODS: Patients and
      their spouses individually completed questionnaires within 1 month of treatment
      initiation (baseline) and at 3- and 6-month follow-up. Distress was measured with
      the Brief Symptom Inventory and caregiving burden with the Caregiver Reaction
      Assessment. RESULTS: Multilevel modeling of data from 158 couples revealed that
      baseline spouses' reports of caregiving-related health problems were
      significantly associated with 3-month (p < 0.001) and 6-month (p = 0.01) follow
      up distress in both patients and spouses even when controlling for baseline
      distress and dyadic adjustment. Furthermore, there was evidence that baseline
      spouses' reports of schedule disruption (p = 0.05) predicted 3-month patients'
      distress and baseline spouses' reports of financial strain (p < 0.05) and lack of
      support (p < 0.10) predicted their own distress at 6 month. CONCLUSION:
      Caregiving burden is problematic for both patients and spouses. Couples in which
      spouses report caregiving-related health problems may be at particular high risk
      of long-term elevated distress. Targets of future couple-focused interventions
      such as self-care and use of social support are discussed.

PMID- 23546538
TI  - Fossil mesostigmatid mites (Mesostigmata: Gamasina, Microgyniina, Uropodina),
      associated with longhorn beetles (Coleoptera: Cerambycidae) in Baltic amber.
AB  - Fossil mesostigmatid mites are extremely rare. Inclusions assignable to the
      tortoise mites (Mesostigmata, Uropodina) are described here for the first time
      from Eocene (ca. 44-49 Ma) Baltic amber. This is the oldest record of Uropodina
      and documents the first unequivocal amber examples potentially assignable to the
      extant genus Uroobovella Berlese, 1903 (Uropodoidea: Urodinychidae). Further
      mites in the same amber pieces are tentatively assigned to Microgynioidea
      (Microgyniina) and Ascidae (Gamasina), both potentially representing the oldest
      records of their respective superfamily and family groups. This new material also
      preserves behavioural ecology in the form of phoretic deutonymphs attached to
      their carriers via a characteristic anal pedicel. These deutonymphs in amber are
      intimately associated with longhorn beetles (Coleoptera: Cerambycidae), probably
      belonging to the extinct species Nothorhina granulicollis Zang, 1905. Modern
      uropodines have been recorded phoretic on species belonging to several beetle
      families, including records of living Uroobovella spp. occurring on longhorn
      beetles. Through these amber inclusions, a uropodine-cerambycid association can
      now be dated back to at least the Eocene.

PMID- 23546539
TI  - PTEN expression and suppression of proliferation are associated with Cdx2
      overexpression in gastric cancer cells.
AB  - The prognosis of gastric cancer (GC) is associated with Cdx2 and nuclear PTEN
      coexpression. This study aimed to determine the expression patterns of Cdx2 and
      PTEN in various GC tissues and cell lines to identify their relationship in GC.
      Immunohistochemistry was undertaken to assess the expression patterns of Cdx2 and
      PTEN in paraffin-embedded specimens of 228 GC patients who had undergone radical
      D2 gastrostomy with long-term follow-up. Cell growth and tumorigenicity were
      analyzed in the BGC823 cells with exogenous Cdx2 and any changes in the
      associated signaling pathways were interpreted in exogenous cdx2 expression and
      cdx2 knockdown. Cdx2 was found in the nuclei of GC cells in 43.4% (99/228) of the
      paraffin-embedded biopsies. A higher expression of nuclear PTEN was observed in
      36.4% (83/228). Coexpression of Cdx2 and nuclear PTEN was detected in GC tumors
      (59/228, 25.9%) which correlated with the prognosis of advanced GC patients
      (p<0.001). The expression levels of Cdx2 and PTEN were variable in the different
      GC cell lines. However, the trends were similar between PTEN and Cdx2 in GC
      tissues and cell lines. High expression of Cdx2 and PTEN significantly reduced
      tumorigenicity in BGC823 cells compared with the empty vector control. Exogenous
      expression of Cdx2 triggered the upregulation of PTEN expression and decreased
      PI3K and pAkt expression and vice versa. The coexpression levels of PTEN and Cdx2
      in GC tumors correlated with prognosis in GC patients. Cdx2 may play a role in
      the upregulation of PTEN by triggering PI3K/Akt inactivation in GC cells.

PMID- 23546540
TI  - Single-enzyme analysis in a droplet-based micro- and nanofluidic system.
AB  - The kinetic activity of individual enzyme molecules was determined in aqueous
      droplets generated in a nano- and microfluidic device. To avoid high background
      noise, the enzyme and substrate solution was confined into femtoliter carriers,
      achieving high product concentrations from single-molecule encapsulation. The
      tiny droplets (phi ~ 2.5-3 MUm) generated from this fluidic system were highly
      monodisperse, beneficial for an analysis of single enzyme activity. The method
      presented here allows to follow large numbers of individual droplets over time.
      The instrumental requirements are furthermore modest, since the small droplet
      size allows to use of standard microscope and standard Pyrex glass chips as well
      as the use of relatively high enzyme concentrations (nM range) for single
      molecule encapsulation.

PMID- 23546541
TI  - Corneomandibular reflex (Wartenberg reflex) in coma: a rarely elicited sign.

PMID- 23546542
TI  - Fast phase formation of double-filled p-type skutterudites by ball-milling and
      hot-pressing.
AB  - Filled-skutterudites are promising mid-temperature thermoelectric materials for
      heat-to-electricity conversion. Traditional preparation methods need a very long
      time annealing (7 to 14 days) to form the right skutterudite phase. Annealing is
      especially critical for p-type filled-skutterudites, since Fe4Sb12 needs filler
      atoms to enter the cage to form a stable phase. In this work, we prepared Ce and
      Nd double-filled p-type skutterudite materials by directly ball-milling the
      quenched ingot without annealing followed by hot-pressing. The results showed
      that with appropriate ball-milling time, a pure p-type filled-skutterudite phase
      can be obtained in just 5 minutes by hot-pressing. The samples prepared in this
      way have the same quality as those prepared by traditional long time annealing
      methods, and showed ZT values above 1 between 700 and 800 K. This simple and
      efficient method is very useful for the preparation of many other materials that
      are kinetically difficult to make.

PMID- 23546543
TI  - Genome-wide analysis of DNA methylation in rat lungs with lipopolysaccharide
      induced acute lung injury.
AB  - Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are
      associated with high morbidity and mortality in patients, however, the precise
      pathogenesis of ALI/ARDS remains unknown. Lipopolysaccharide (LPS) exhibits a
      number of critical functions and may be associated with the DNA methylation of
      genes in the lungs. In the present study a genome-wide analysis of DNA
      methylation was performed in rat lungs with LPS-induced ALI/ARDS. Normal and LPS
      induced lung tissues with ALI were analyzed using methylated DNA
      immunoprecipitation and a rat DNA methylation promoter plus CpG island microarray
      and the candidate genes were validated by quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR). Aberrant DNA methylation of the promoter
      regions of 1,721 genes and the CpG islands of 990 genes was identified when
      normal lung tissues and lung tissues with LPS-induced ALI/ARDS were compared.
      These genes were commonly located on chromosomes 1, 3, 5, 7 and 10 (P<0.01).
      Methylation level and CpG density were compared and it was found that genes
      associated with high CpG density promoters had a high ratio of methylation.
      Furthermore, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis. In addition, three genes (Mapk3, Pak1 and Rac2)
      were validated in the control and lung tissues with ALI by RT-PCR. The results
      indicate that aberrant DNA methylation of lung tissues may be involved in the
      pathophysiology of LPS-induced ALI/ARDS. Future studies are required to evaluate
      the therapeutic and prognostic value of the current novel observations in
      ALI/ARDS.

PMID- 23546544
TI  - Prognostic implication of infiltrative growth pattern and establishment of novel
      risk stratification model for survival in patients with upper urinary tract
      urothelial carcinoma.
AB  - PURPOSE: To investigate the prognostic significance of infiltrative growth
      pattern (INF) and to develop a novel risk stratification model for disease
      specific survival (DSS) in patients with upper urinary tract urothelial carcinoma
      (UTUC). METHODS: This study included 113 patients with UTUC treated with radical
      nephroureterectomy. Pathological features, including INF, were compared with DSS.
      INF was classified into 3 patterns (INFa, INFb, and INFc). The prognostic factors
      of DSS were evaluated with univariate and multivariate Cox proportional hazard
      model analyses. A risk stratification model based on the relative risks of DSS
      was then established. RESULT: Univariate analysis revealed that patients with
      high-grade tumor, pathological T stage >=T3, a non-expanding infiltration pattern
      (INF >=b), sessile-type carcinoma, the presence of lymphovascular invasion and
      positive lymph node involvement showed significantly lower survival rates than
      their respective counterparts. In the multivariate analysis, high grade tumor,
      positive lymph node involvement and INF >=b were independent predictors for DSS
      (p < 0.05). The patients were stratified into 3 risk groups. The 5-year DSS rates
      were 94.4 % in the low-risk group, 67.5 % in the intermediate-risk group and 20.5
      % in the high-risk group. CONCLUSION: In addition to lymph node involvement and
      pathological tumor grade, INF is a novel independent prognostic factor in
      patients with UTUC treated with radical nephroureterectomy. Our risk
      stratification model developed using these 3 factors may help clinicians identify
      patients with a poor prognosis who might be good candidates for clinical trials
      of innovative therapies.

PMID- 23546545
TI  - Feasibility of extended-field irradiation and intracavitary brachytherapy
      combined with weekly cisplatin chemosensitization for IB2-IIIB cervical cancer
      with positive paraaortic or high common iliac lymph nodes: a retrospective
      review.
AB  - BACKGROUND: The aim of this retrospective study was to investigate the
      feasibility of primary treatment with extended-field irradiation and weekly
      cisplatin (extended-field concurrent chemoradiotherapy, EFCCRT) as initial
      therapy in patients with International Federation of Gynecology and Obstetrics
      IB1 to IIIB cervical cancer with paraaortic or high common iliac lymph node
      metastases. METHODS: Participants comprised patients with confirmed cervical
      cancer, showing paraaortic or high common iliac lymph node metastases on
      diagnostic imaging, treated with EFCCRT. Total external radiation doses were 50.4
      Gy to the whole pelvis and 45.0 Gy to the lumbar paraaortic region. High-dose
      rate intracavitary brachytherapy was performed to deliver a total dose of 18-24
      Gy in 6-Gy fractions prescribed at point A. Weekly cisplatin (30-40 mg/m(2)) was
      given concurrently with radiotherapy. RESULTS: Twenty-four patients were treated.
      Median follow-up interval was 34 months. The dose of cisplatin was 30 mg/m(2) in
      2 cases, 35 mg/m(2) in 8 cases, and 40 mg/m(2) in 14 cases. Twenty-two cases (92
      %) received more than 160 mg/m(2) cisplatin. Ten cases (42 %) experienced acute
      grade 3/4 hematological toxicity, and 9 cases (38 %) experienced acute grade 3
      nonhematological toxicity. No case presented late grade 3/4 toxicity. Three-year
      progression-free and overall survival rates were 54 % and 72 %, respectively.
      Eleven cases recurred during follow-up. Sites of recurrence were within the
      irradiation field in 4 cases, outside the field in 6 cases, and in both fields in
      1 case. CONCLUSION: EFCCRT and high-dose-rate intracavitary brachytherapy for
      patients with paraaortic or high common iliac lymph node metastases from cervical
      cancer is feasible.

PMID- 23546546
TI  - Pathological outcomes of Japanese men eligible for active surveillance after
      radical prostatectomy.
AB  - BACKGROUND: The aim of this study was to analyze the pathological features of
      prostatectomy specimens from patients with low-risk prostate cancer eligible for
      active surveillance (AS) and evaluate preoperative data suitable for predicting
      upstaged (>=pT3) or upgraded disease (Gleason score of >=7), defined as
      'reclassification'. METHODS: A retrospective analysis of 521 consecutive radical
      prostatectomy procedures (January 2005 through to December 2011) performed at our
      institution without neoadjuvant hormonal therapy was performed. Eighty-four
      patients fulfilled the following criteria-clinical T1 or T2 disease, prostate
      specific antigen (PSA) level of <=10 ng/ml, one or two positive biopsies, and
      Gleason score of <7. Clinicopathological features at diagnosis were compared
      between patients with and without reclassification after radical prostatectomy.
      RESULTS: Forty of 84 patients (47.6 %) had a Gleason score of >=7, and 8 (9.5 %)
      had upstaged disease (>=pT3). Seven patients with upstaged disease also showed
      upgraded reclassification. Two patients with reclassification showed biochemical
      recurrence at 59 and 89 months after surgery, respectively. Preoperative
      parameters evaluated included age, PSA level, PSA density (PSAD), clinical T
      stage, and number and percentage of positive prostate cores. Among 82 patients
      with complete data, univariate analysis showed that PSAD (ng/ml(2)) was a
      significant parameter to discriminate patients with reclassified disease and
      those without reclassified disease (p < 0.001). Multivariate analysis revealed
      that PSAD was the only independent variable to predict disease with
      reclassification (p = 0.006). CONCLUSIONS: Preoperative PSAD may be a good
      indicator for selecting patients eligible for AS in the Japanese population.

PMID- 23546547
TI  - Functional mapping of the circuits involved in the expression of contextual fear
      responses in socially defeated animals.
AB  - In this study, we have aimed at outlining the neural systems underlying the
      expression of contextual fear to social defeat. First, we have developed an
      experimental procedure, where defeated animals could express, without the
      presence of a dominant aggressive male, robust and reliable conditioned fear
      responses to the context associated with social defeat. Next, by examining the
      pattern of Fos expression, we have been able to outline a brain circuit
      comprising septal and amygdalar sites, as well as downstream hypothalamic paths,
      putatively involved in the expression of contextual fear to social threat. Of
      particular relevance, we have found that exposure to a defeat-associated context
      results in a striking Fos up-regulation in the dorsomedial part of the dorsal
      premammillary nucleus (PMDdm). To further understand the role of the PMDdm in the
      circuit organizing conditioned fear to social threats, we have been able to
      observe that pharmacological blockade of the PMDdm reduced fear responses to a
      social defeat-associated context. Next, we observed that pharmacological blockade
      of the dorsomedial part of the periaqueductal gray, one of the main targets of
      the PMDdm, produced an even higher reduction of conditioned fear in defeated
      intruders, and appears as an important node for the expression of contextual
      defensive responses to social threats. The present results help to elucidate the
      basic organization of the neural circuits underlying contextual conditioned
      responses to social defeat, and reveal that they share at least part of the same
      circuit involved in innate responses to social defeat to an aggressive
      conspecific. 

PMID- 23546548
TI  - TiO2 coated Au/Ag nanorods with enhanced photocatalytic activity under visible
      light irradiation.
AB  - A facile method was used to prepare uniform Au NR/TiO2 and Au/Ag NR/TiO2 core
      shell composite nanoparticles. Au/Ag NR/TiO2 nanoparticles were found to display
      significantly enhanced visible light photo-catalytic activity compared to Au
      NR/TiO2 and the commercially available TiO2 nanoparticles. The enhancement
      mechanism was ascribed to injection of hot electrons of photo-excited Au/Ag NRs
      to TiO2, which was confirmed by 633 nm laser induced reduction of silver ions on
      the surface of Au/Ag NR/TiO2 composite nanoparticles.

PMID- 23546549
TI  - Large shape-persistent metal-invertible 15-Nsp(2)-donor-atom macrocycles
      functioning as trinucleating ligands.
AB  - Reaction of 4,6-dihydrazinopyrimidines with 2,6-dicarbonylpyridines produces,
      under metal-free or template conditions, a new class of [3 + 3] macrocycles with
      15 Nsp(2) donor atoms. Nine Nsp(2) atoms are on the external circumference of the
      macrocycle. The macrocycle can bind metal ions and produce trinuclear complexes
      along with the motion of the nine outer Nsp(2) atoms to inner positions (a motion
      of inversion of the macrocycle).

PMID- 23546551
TI  - Accountable care organizations in pediatrics: irrelevant or a game changer for
      children?

PMID- 23546552
TI  - Trends in breast cancer incidence and mortality in the United States:
      implications for prevention.
AB  - While debate continues regarding short-term changes in breast cancer incidence
      and the impact of screening on mortality, a long-term view of trends in incidence
      and mortality may better inform our understanding of the changing patterns of
      disease and ultimately guide in population-based prevention. Although many
      factors have influenced breast cancer incidence over the past seven decades, some
      have played more prominent roles at various times. Changing reproductive
      patterns, greater longevity, and post-menopausal hormone (estrogen +
      progesterone) were important in the steady increase before 1980, while
      mammographic screening, probably in conjunction with escalating combined estrogen
      + progesterone use, played dominant roles in the post-1980 surge. Accruing
      evidence also indicates that the rapid drop in 2003 was mostly due to a sharp
      decline in estrogen + progesterone use. The most paradoxical observation relates
      to the divergence in incidence and mortality trends most noticeable when
      mortality rates started to decline shortly after the surge in incidence rates
      started in 1980. In addition to the dynamic changes in risk factor profiles, the
      divergence reflects wider uptake of screening mammography, better
      characterization of tumor biology, and improvements in treatment. The rise in
      incidence rates over the past three decades is due to an increase in estrogen
      receptor positive (ER+) tumors, which respond favorably to treatment. On the
      other hand, the incidence of estrogen receptor negative (ER-) tumors, which
      respond poorly to hormonal therapy, has been decreasing for almost three decades.
      Furthermore, widespread adoption of screening mammography has led to tumors being
      diagnosed at earlier stages when treatment is effective and advances in treatment
      have ensured adoption of targeted and better tolerated therapies. To achieve long
      term success in the primary prevention of breast cancer, a greater understanding
      of factors responsible for the decrease in ER- tumors is essential. In addition,
      improving the sensitivity of breast cancer screening to facilitate earlier
      detection of tumors with very aggressive phenotypes would go a long way in
      bridging the divergence between incidence and mortality.

PMID- 23546553
TI  - Genetic associations with toxicity-related discontinuation of aromatase inhibitor
      therapy for breast cancer.
AB  - Up to 25 % of patients discontinue adjuvant aromatase inhibitor (AI) therapy due
      to intolerable symptoms. Predictors of which patients will be unable to tolerate
      these medications have not been defined. We hypothesized that inherited variants
      in candidate genes are associated with treatment discontinuation because of AI
      associated toxicity. We prospectively evaluated reasons for treatment
      discontinuation in women with hormone receptor-positive breast cancer initiating
      adjuvant AI through a multicenter, prospective, randomized clinical trial of
      exemestane versus letrozole. Using multiple genetic models, we evaluated
      potential associations between discontinuation of AI therapy because of toxicity
      and 138 variants in 24 candidate genes, selected a priori, primarily with roles
      in estrogen metabolism and signaling. To account for multiple comparisons,
      statistical significance was defined as p < 0.00036. Of the 467 enrolled patients
      with available germline DNA, 152 (33 %) discontinued AI therapy because of
      toxicity. Using a recessive statistical model, an intronic variant in ESR1
      (rs9322336) was associated with increased risk of musculoskeletal toxicity
      related exemestane discontinuation [HR 5.0 (95 % CI 2.1-11.8), p < 0.0002]. An
      inherited variant potentially affecting estrogen signaling may be associated with
      exemestane-associated toxicity, which could partially account for intra-patient
      differences in AI tolerability. Validation of this finding is required.

PMID- 23546554
TI  - Feasibility of increasing access to healthy foods in neighborhood corner stores.
AB  - The feasibility of working with neighborhood corner stores to increase the
      availability of fresh fruit and vegetables in low-income neighborhoods in New
      Orleans was assessed. Household interviews and 24-hour dietary recalls (n = 97),
      corner store customer intercept interviews (n = 60) and interviews with corner
      store operators (owners/managers) (n = 12) were conducted in three neighborhoods
      without supermarkets. Regional produce wholesalers were contacted by phone.
      Results indicated that the majority of neighborhood residents use supermarkets or
      super stores as their primary food source. Those who did shop at corner stores
      typically purchased prepared foods and/or beverages making up nearly one third of
      their daily energy intake. Most individuals would be likely to purchase fresh
      fruit and vegetables from the corner stores if these foods were offered. Store
      operators identified cost, infrastructure and lack of customer demand as major
      barriers to stocking more fresh produce. Produce wholesalers did not see much
      business opportunity in supplying fresh produce to neighborhood corner stores on
      a small scale. Increasing availability of fresh fruit and vegetables in corner
      stores may be more feasible with the addition of systems changes that provide
      incentives and make it easier for neighborhood corner stores to stock and sell
      fresh produce. 

PMID- 23546555
TI  - Adherence to repeat fecal occult blood testing in an urban community health
      center network.
AB  - Annual fecal occult blood testing (FOBT) has the potential to reduce colorectal
      cancer mortality, but in practice it is challenging to complete FOBT every year.
      Repeat FOBT adherence may be especially low in community health center (CHC)
      settings, where many patients face barriers to annual FOBT completion. We
      conducted a retrospective cohort analysis to investigate adherence to annual FOBT
      in an urban CHC network that serves a predominantly Spanish-speaking, uninsured
      adult patient population. This study used data from the two-year period between
      January 2010 and December 2011, and included adults aged 50-74 who completed a
      screening FOBT with a negative result during the first 6 months of 2010. We
      examined whether each patient completed a second FOBT between 9 and 18 months
      after the initial negative FOBT, and tested whether repeat FOBT adherence was
      associated with patient characteristics or the number of clinic visits after the
      initial negative FOBT. Only 69 of 281 included patients completed repeat FOBT
      (24.6 % adherence), and none of 62 patients (0 %) with 0 clinic visits completed
      repeat FOBT. We detected no significant differences in adherence by age, sex,
      preferred language, insurance status, or number of chronic conditions. In
      multivariable regression, the adjusted relative risk of repeat FOBT was 1.66 (95
      % CI 1.09-2.54; p = 0.02) among patients with 3 or more clinic visits (referent:
      patients with 1-2 visits). The observed low rate of adherence greatly diminishes
      the effectiveness of FOBT in reducing CRC mortality. Findings demonstrate the
      need for systems-based interventions that increase adherence without requiring
      face-to-face encounters. 

PMID- 23546556
TI  - Repression of exogenous gene expression by the retinoic acid target gene G0S2.
AB  - The G0/G1 switch gene 2 (G0S2) is rapidly induced by all-trans-retinoic acid (RA)
      treatment of acute promyelocytic leukemia (APL) and other cells. G0S2 regulates
      lipolysis via inhibition of adipose triglyceride lipase (ATGL). This study found
      that retinoic acid receptor (RAR), but not retinoid X receptor (RXR) agonists
      induced G0S2 expression in APL cells. Novel G0S2 functions were uncovered that
      included repression of exogenous gene expression and transcriptional activity.
      Transient G0S2 transfection repressed the activities of multiple reporter
      constructs (including the retinoid-regulated species RARbeta, UBE1L and G0S2);
      this occurred in diverse cell contexts. This inhibition was antagonized by siRNA
      mediated G0S2 knockdown. To determine the inhibitory effects were not due to
      transient G0S2 expression, G0S2 was stably overexpressed in cells without
      appreciable basal G0S2 expression. As expected, this repressed transcriptional
      activities. Intriguingly, transfection of G0S2 did not affect endogenous RARbeta,
      UBE1L or G0S2 expression. Hence, only exogenously expressed genes were affected
      by G0S2. The domain responsible for this repression was localized to the G0S2
      hydrophobic domain (HD). This was the same region responsible for the ability of
      G0S2 to inhibit ATGL activity. Whether an interaction with ATGL accounted for
      this new G0S2 activity was studied. Mimicking the inhibition of ATGL by oleic
      acid treatment that increased lipid droplet size or ATGL siRNA knockdown did not
      recapitulate G0S2 repressive effects. Engineered gain of ATGL expression did not
      rescue G0S2 transcriptional repression either. Thus, transcriptional repression
      by G0S2 did not depend on the ability of G0S2 to inhibit ATGL. Subcellular
      localization studies revealed that endogenous and exogenously-expressed G0S2
      proteins were localized to the cytoplasm, particularly in the perinuclear region.
      Expression of a mutant G0S2 species that lacked the HD domain altered cytosolic
      G0S2 localization. This linked G0S2 subcellular localization to G0S2
      transcriptional repression. The potential mechanisms responsible for this G0S2
      repression are examined.

PMID- 23546557
TI  - Evaluation of diagnostic criteria for Crohn's disease in Japan.
AB  - BACKGROUND: In Japan, Crohn's disease (CD) is diagnosed according to a single,
      well-established set of diagnostic criteria. However, no nationwide attempt has
      been made to determine which specific criteria within these diagnostic criteria
      are used to make diagnoses. METHODS: A questionnaire-based survey was conducted
      of patients given a definitive or suspected diagnosis of CD before January 2011
      according to the Japanese Diagnostic Criteria for Crohn's Disease. The survey
      included 579 patients with a definitive diagnosis of CD and 59 patients with a
      suspected diagnosis of CD at 34 Japanese medical institutions. RESULTS: A total
      of 87.4 % of definitive diagnoses of CD were based on the criterion in the
      definite category: major finding A "longitudinal ulcer (LU)" or B "cobblestone
      like appearance (CSA)". A total of 30.4 % of definitive diagnoses were based on
      the criterion: major finding C "non-caseating epithelioid cell granuloma (NCEG)"
      with minor finding a "irregularshaped and/or quasi-circular ulcers or aphthous
      ulcerations found extensively in the gastrointestinal tract" or b "characteristic
      perianal lesions". Finally, 7.1 % of definitive diagnoses were made according to
      the criterion: all minor findings a, b and c "characteristic gastric and/or
      duodenal lesions". Among suspected diagnoses of CD, 74.6 % were based on the
      criterion in the suspected category: one or two minor findings. CONCLUSIONS: The
      Japanese diagnostic criteria for Crohn's disease consist of combinations of
      specific morphological findings. Many of the diagnoses were based on the findings
      of LU or CSA.

PMID- 23546558
TI  - Availability of monitoring serum HBV DNA plus RNA during nucleot(s)ide analogue
      therapy.

PMID- 23546559
TI  - Comparison of nitrous oxide to no sedation and deep sedation for diagnostic upper
      gastrointestinal endoscopy.
AB  - BACKGROUND: In China, great efforts are dedicated to reducing discomfort and
      minimizing undesirable complications for patients undergoing upper
      gastrointestinal (UGI) endoscopy. METHODS: This study was conducted to compare
      the diagnostic accuracy, safety, complications, and patient and examiner
      satisfaction for different sedation approaches. We carried out a prospective and
      randomized study on 450 patients undergoing diagnostic UGI endoscopy. During the
      procedure, patients received N(2)O by inhalation; an intravenous mixture of
      midazolam, remifentanil, and propofol; or no sedative. The cardiorespiratory
      functions, procedure duration, recovery time, length of hospital stay,
      complications, and ratings of patient and examiner satisfaction were recorded.
      RESULTS: Compared to those deeply sedated, patients inhaling N(2)O had comparable
      diagnostic accuracy, significantly shorter procedure and recovery times, a lower
      risk of cardiorespiratory distress, but a higher number of minor complications
      and post-procedure mental issues. The procedural satisfaction ratings were
      highest for those receiving deep sedation; fewer patients reported willingness to
      reconsider N(2)O for a future upper GI endoscopy. The lowest satisfaction rating
      was given by those who received no sedation. CONCLUSIONS: Multiple factors should
      be considered before selecting N(2)O as the sedative for diagnostic UGI
      endoscopy, including the patient's economic status, potential risk of
      cardiorespiratory distress, and sensitivity to potential adverse effects of N(2)O
      administration.

PMID- 23546560
TI  - The role of minimally invasive percutaneous embolisation technique in the
      management of bleeding stomal varices.
AB  - INTRODUCTION: Stomal varices can develop in patients with ostomy in the setting
      of portal hypertension. Bleeding from the stomal varices is uncommon, but the
      consequences can be disastrous. Haemorrhage control measures that have been
      described in the literature include pressure dressings, stomal revision,
      mucocutaneous disconnection, variceal suture ligation and sclerotherapy. These
      methods may only serve to temporise the stomal bleeding and have a high risk of
      recurrent bleed. While transjugular intrahepatic porto-systemic shunting has been
      advocated as the treatment of choice in patients with underlying liver cirrhosis,
      histoacryl glue or coil embolisation has been successfully employed in patients
      who are not suitable candidates for TIPS. METHODS AND RESULTS: Direct
      percutaneous embolisation of the dominant varices was performed successfully
      under ultrasound and fluoroscopic guidance in two patients using a combination of
      coils and histoacryl glue. RESULTS: While transjugular intrahepatic porto
      systemic shunting has been advocated as the treatment of choice in patients with
      underlying liver cirrhosis, histoacryl glue or coil embolisation has been
      successfully employed in patients who are not suitable candidates for TIPS.
      CONCLUSION: Direct percutaneous embolisation is a safe and effective treatment
      for stomal varices in selected patients.

PMID- 23546561
TI  - Endoscopic ultrasound in staging esophageal cancer after neoadjuvant chemotherapy
      -results of a multicenter cohort analysis.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is considered a gold standard in the
      initial staging of esophageal cancer. There is an ongoing debate whether EUS is
      useful for tumor staging after neoadjuvant chemotherapy (NAC). METHODS: Ninety
      five patients with esophageal cancer were retrospectively analyzed. In 45
      patients, EUS was performed prior to and after NAC, while 50 patients had no
      induction therapy. Histological correlation through surgery was available. uT/uN
      classifications were compared to pT/pN stages. Statistical analysis included
      calculation of sensitivity, specificity, and accuracy rates. Agreement between
      endosonography and T staging was assessed with Cohen's kappa statistics. RESULTS:
      For those patients with prior NAC, overall accuracy of yuT and yuN classification
      was 29 and 62%, respectively. Sensitivity, specificity, and accuracy rates for
      local tumor extension after NAC were as follows (%): T1: -/97/84, T2: 13/76/53,
      T3:86/29/46, T4:20/100/91, T1/2: 27/83/56, T3/4: 89/31/56. Cohen's kappa
      indicated poor agreement (kappa = 0.129) between yuT classification and ypT
      stage. Relative to positive lymph node detection, sensitivity and specificity
      were 100 and 6%, respectively (kappa = 0.06). T stage was overstaged in 23 (51%)
      and understaged in seven (16%) patients. CONCLUSION: EUS is an unreliable tool
      for staging esophageal cancer after NAC. Overstaging of the T stage is common
      after NAC.

PMID- 23546562
TI  - Individual- versus group-based financial incentives for weight loss: a
      randomized, controlled trial.
AB  - BACKGROUND: Data on the effectiveness of employer-sponsored financial incentives
      for employee weight loss are limited. OBJECTIVE: To test the effectiveness of 2
      financial incentive designs for promoting weight loss among obese employees.
      DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT01208350) SETTING:
      Children's Hospital of Philadelphia. PARTICIPANTS: 105 employees with a body mass
      index between 30 and 40 kg/m2. INTERVENTION: 24 weeks of monthly weigh-ins
      (control group; n = 35); individual incentive, designed as $100 per person per
      month for meeting or exceeding weight-loss goals (n = 35); and group incentive,
      designed as $500 per month split among participants within groups of 5 who met or
      exceeded weight-loss goals (n = 35). MEASUREMENTS: Weight loss after 24 weeks
      (primary outcome) and 36 weeks and changes in behavioral mediators of weight loss
      (secondary outcomes). RESULTS: Group-incentive participants lost more weight than
      control participants (mean between-group difference, 4.4 kg [95% CI, 2.0 to 6.7
      kg]; P < 0.001) and individual-incentive participants (mean between-group
      difference, 3.2 kg [CI, 0.9 to 5.5 kg]; P = 0.008). Twelve weeks after incentives
      ended and after adjustment for 3-group comparisons, group-incentive participants
      maintained greater weight loss than control group participants (mean between
      group difference, 2.9 kg [CI, 0.5 to 5.3 kg]; P = 0.016) but not greater than
      individual-incentive participants (mean between-group difference, 2.7 kg [CI, 0.4
      to 5.0 kg]; P = 0.024). LIMITATION: Single employer and short follow-up.
      CONCLUSION: A group-based financial incentive was more effective than an
      individual incentive and monthly weigh-ins at promoting weight loss among obese
      employees at 24 weeks. PRIMARY FUNDING SOURCE: National Institute on Aging.

PMID- 23546563
TI  - Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific
      mortality in older adults: a cohort study.
AB  - BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids (omega3-PUFAs),
      including eicosapentaenoic acid (EPA) (20:5omega-3), docosapentaenoic acid (DPA)
      (22:5omega-3), and docosahexaenoic acid (DHA) (22:6omega-3), have been shown to
      reduce cardiovascular risk, but effects on cause-specific and total mortality and
      potential dose-responses remain controversial. Most observational studies have
      assessed self-reported dietary intake and most randomized trials have tested
      effects of adding supplements to dietary intake and evaluated secondary
      prevention, thus limiting inference for dietary omega3-PUFAs or primary
      prevention. OBJECTIVE: To investigate associations of plasma phospholipid EPA,
      DPA, DHA, and total omega3-PUFA levels with total and cause-specific mortality
      among healthy older adults not receiving supplements. DESIGN: Prospective cohort
      study. SETTING: 4 U.S. communities. PARTICIPANTS: 2692 U.S. adults aged 74 years
      (+/-5 years) without prevalent coronary heart disease (CHD), stroke, or heart
      failure at baseline. MEASUREMENTS: Phospholipid fatty acid levels and
      cardiovascular risk factors were measured in 1992. Relationships with total and
      cause-specific mortality and incident fatal or nonfatal CHD and stroke through
      2008 were assessed. RESULTS: During 30 829 person-years, 1625 deaths (including
      570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal
      and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of
      omega3-PUFA biomarkers were associated with lower total mortality, with extreme
      quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend =
      0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI,
      0.67 to 0.94; P for trend = 0.006), and 0.73 for total omega3-PUFAs (CI, 0.61 to
      0.86; P for trend < 0.001). Lower risk was largely attributable to fewer
      cardiovascular than noncardiovascular deaths. Individuals in the highest quintile
      of phospholipid omega3-PUFA level lived an average of 2.22 more years (CI, 0.75
      to 3.13 years) after age 65 years than did those in the lowest quintile.
      LIMITATION: Temporal changes in fatty acid levels and misclassification of causes
      of death may have resulted in underestimated associations, and unmeasured or
      imperfectly measured covariates may have caused residual confounding. CONCLUSION:
      Higher circulating individual and total omega3-PUFA levels are associated with
      lower total mortality, especially CHD death, in older adults. PRIMARY FUNDING
      SOURCE: National Institutes of Health.

PMID- 23546565
TI  - Medical management to prevent recurrent nephrolithiasis in adults: a systematic
      review for an American College of Physicians Clinical Guideline.
AB  - BACKGROUND: Optimum management to prevent recurrent kidney stones is uncertain.
      PURPOSE: To evaluate the benefits and harms of interventions to prevent recurrent
      kidney stones. DATA SOURCES: MEDLINE, Cochrane, and other databases through
      September 2012 and reference lists of systematic reviews and randomized,
      controlled trials (RCTs). STUDY SELECTION: 28 English-language RCTs that studied
      treatments to prevent recurrent kidney stones and reported stone outcomes. DATA
      EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2
      independently rated quality and graded strength of evidence. DATA SYNTHESIS: In
      patients with 1 past calcium stone, low-strength evidence showed that increased
      fluid intake halved recurrent composite stone risk compared with no treatment
      (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed
      that reducing soft-drink consumption decreased recurrent symptomatic stone risk
      (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones,
      most of whom were receiving increased fluid intake, moderate-strength evidence
      showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14
      to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced
      composite stone recurrence risk compared with placebo or control, although the
      benefit from allopurinol seemed limited to patients with baseline hyperuricemia
      or hyperuricosuria. Other baseline biochemistry measures did not allow prediction
      of treatment efficacy. Low-strength evidence showed that neither citrate nor
      allopurinol combined with thiazide was superior to thiazide alone. There were few
      withdrawals among patients with increased fluid intake, many among those with
      other dietary interventions and more among those who received thiazide and
      citrate than among control patients. Reporting of adverse events was poor.
      LIMITATIONS: Most trial participants had idiopathic calcium stones. Nearly all
      studies reported a composite (including asymptomatic) stone recurrence outcome.
      CONCLUSION: In patients with 1 past calcium stone, increased fluid intake reduced
      recurrence risk. In patients with multiple past calcium stones, addition of
      thiazide, citrate, or allopurinol further reduced risk. PRIMARY FUNDING SOURCE:
      Agency for Healthcare Research and Quality.

PMID- 23546566
TI  - Empirical evidence of the importance of comparative studies of diagnostic test
      accuracy.
AB  - BACKGROUND: Systematic reviews that "compare" the accuracy of 2 or more tests
      often include different sets of studies for each test. PURPOSE: To investigate
      the availability of direct comparative studies of test accuracy and to assess
      whether summary estimates of accuracy differ between meta-analyses of
      noncomparative and comparative studies. DATA SOURCES: Systematic reviews in any
      language from the Database of Abstracts of Reviews of Effects and the Cochrane
      Database of Systematic Reviews from 1994 to October 2012. STUDY SELECTION: 1 of 2
      assessors selected reviews that evaluated at least 2 tests and identified meta
      analyses that included both noncomparative studies and comparative studies. DATA
      EXTRACTION: 1 of 3 assessors extracted data about review and study
      characteristics and test performance. DATA SYNTHESIS: 248 reviews compared test
      accuracy; of the 6915 studies, 2113 (31%) were comparative. Thirty-six reviews
      (with 52 meta-analyses) had adequate studies to compare results of noncomparative
      and comparative studies by using a hierarchical summary receiver-operating
      characteristic meta-regression model for each test comparison. In 10 meta
      analyses, noncomparative studies ranked tests in the opposite order of
      comparative studies. A total of 25 meta-analyses showed more than a 2-fold
      discrepancy in the relative diagnostic odds ratio between noncomparative and
      comparative studies. Differences in accuracy estimates between noncomparative and
      comparative studies were greater than expected by chance (P < 0.001). LIMITATION:
      A paucity of comparative studies limited exploration of direction in bias.
      CONCLUSION: Evidence derived from noncomparative studies often differs from that
      derived from comparative studies. Robustly designed studies in which all patients
      receive all tests or are randomly assigned to receive one or other of the tests
      should be more routinely undertaken and are preferred for evidence to guide test
      selection. PRIMARY FUNDING SOURCE: National Institute for Health Research (United
      Kingdom).

PMID- 23546567
TI  - Preventing fungal disease in chronically immunosuppressed outpatients: time for
      action?

PMID- 23546564
TI  - Discontinuation of statins in routine care settings: a cohort study.
AB  - BACKGROUND: Systematic data on discontinuation of statins in routine practice of
      medicine are limited. OBJECTIVE: To investigate the reasons for statin
      discontinuation and the role of statin-related events (clinical events or
      symptoms believed to have been caused by statins) in routine care settings.
      DESIGN: A retrospective cohort study. SETTING: Practices affiliated with Brigham
      and Women's Hospital and Massachusetts General Hospital in Boston. PATIENTS:
      Adults who received a statin prescription between 1 January 2000 and 31 December
      2008. MEASUREMENTS: Information on reasons for statin discontinuations was
      obtained from a combination of structured electronic medical record entries and
      analysis of electronic provider notes by validated software. RESULTS: Statins
      were discontinued at least temporarily for 57 292 of 107 835 patients. Statin
      related events were documented for 18 778 (17.4%) patients. Of these, 11 124 had
      statins discontinued at least temporarily; 6579 were rechallenged with a statin
      over the subsequent 12 months. Most patients who were rechallenged (92.2%) were
      still taking a statin 12 months after the statin-related event. Among the 2721
      patients who were rechallenged with the same statin to which they had a statin
      related event, 1295 were receiving the same statin 12 months later, and 996 of
      them were receiving the same or a higher dose. LIMITATIONS: Statin
      discontinuations and statin-related events were assessed in practices affiliated
      with 2 academic medical centers. Utilization of secondary data could have led to
      missing or misinterpreted data. Natural-language-processing tools used to
      compensate for the low (30%) proportion of reasons for statin discontinuation
      documented in structured electronic medical record fields are not perfectly
      accurate. CONCLUSION: Statin-related events are commonly reported and often lead
      to statin discontinuation. However, most patients who are rechallenged can
      tolerate statins long-term. This suggests that many of the statin-related events
      may have other causes, are tolerable, or may be specific to individual statins
      rather than the entire drug class. PRIMARY FUNDING SOURCE: National Library of
      Medicine, Diabetes Action Research and Education Foundation, and Chinese National
      Key Program of Clinical Science.

PMID- 23546569
TI  - Statin discontinuation and intolerance: the challenge of lifelong therapy.

PMID- 23546568
TI  - Getting the most out of financial incentives for weight loss.

PMID- 23546570
TI  - Shirts and skins.

PMID- 23546571
TI  - Don't read this article.

PMID- 23546572
TI  - Family heroes.

PMID- 23546573
TI  - Predictive accuracy of the Liverpool Lung Project risk model.

PMID- 23546574
TI  - In response. Predictive accuracy of the Liverpool Lung Project risk model.

PMID- 23546575
TI  - Effects of testosterone replacement on response to sildenafil citrate.

PMID- 23546576
TI  - Effects of testosterone replacement on response to sildenafil citrate.

PMID- 23546577
TI  - Effects of testosterone replacement on response to sildenafil citrate.

PMID- 23546578
TI  - In response. Effects of testosterone replacement on response to sildenafil
      citrate.

PMID- 23546579
TI  - In response. Dispensing of electronically discontinued medications.

PMID- 23546580
TI  - Dispensing of electronically discontinued medications.

PMID- 23546582
TI  - Summaries for patients. Discontinuation of statins.

PMID- 23546583
TI  - In the clinic. Hearing loss.

PMID- 23546584
TI  - [Frontiers in researches of immune regulators].

PMID- 23546585
TI  - [Role of adaptor molecule Gab2 in mast cell-mediated allergy response].
AB  - Mast cells are major players in allergic responses. IgE-dependent activation
      through Fc epsilon RI leads to degranulation and cytokine production, both of
      which require Gab2. To clarify how the signals diverge at Gab2, we established
      Gab2 knock-in mice that express Gab2 mutated at either the PI-3K- or SHP-2
      binding sites. Examination of these mutants showed that both binding sites were
      required for the degranulation and anaphylaxis response, but not for cytokine
      production or contact hypersensitivity. Furthermore, the PI-3K- but not the SHP-2
      binding site was important for granule translocation during degranulation. We
      also identified a small GTPase, ARF1, as the downstream target of PI-3K that
      regulates granule translocation. Fc epsilon RI-stimulation induced ARF1
      activation, and this response was dependent on Fyn and the PI-3K-binding site of
      Gab2. ARF1 activity was required for the Fc epsilon RI-mediated granule
      translocation. These results indicate that Fyn/Gab2/PI-3K/ARF1-mediated signaling
      is specifically involved in granule translocation and the anaphylaxis response.
      In this review, I discussed how Gab2 controls biological events especially for
      mast cell degranulation and allergy response.

PMID- 23546586
TI  - [Role of STIM-dependent Ca(2+) influx in regulatory B cells].
AB  - B cells positively regulate immune responses through antibody production and
      effector T cell differentiation. In addition to such protective roles against
      pathogenesis, B cells also serve as negative regulators of autoimmunity by
      secreting an anti-inflammatory cytokine, interleukin-10 (IL-10). These B cell
      functions are caused by encountering their cognate antigens through their B cell
      receptors (BCR). A central response of BCR stimulation is intracellular Ca(2+)
      elevation, which is derived mainly from two pathways, Ca(2+) release from
      endoplasmic reticulum (ER) stores and Ca(2+) influx from the extracellular space
      across the plasma membrane. Although a chief Ca(2+) entry pathway in immune cells
      is store-operated Ca(2+) (SOC) influx, which is triggered by depletion of Ca(2+)
      from ER, its physiological role in B cells remains elusive. Stromal interaction
      molecules (STIM), which consist of STIM1 and its homolog, STIM2, serve as ER
      calcium sensors and are essential for SOC influx after antigen stimulation. We
      have recently found that STIM1- and STIM2-induced SOC influx is critical for
      regulatory B cell function required to limit experimental autoimmune
      encephalomyelitis (EAE), a mouse model of multiple sclerosis. Even through
      several B cell populations have been reported to suppress inflammation of
      autoimmune diseases through production of IL-10, which subset of them exerts
      their regulatory function during EAE is not fully understood. This review focuses
      on our recent progress in the role of STIM-dependent SOC influx as a key signal
      for B cell regulatory function and the latest findings for understanding how
      regulatory B cells suppress the development of EAE.

PMID- 23546587
TI  - [Understanding of immune system by visualization of spatiotemporal regulation of
      immune cells in the entire body].
AB  - Immune system is high-dimensional integrated system distributed in the whole
      body. Many kinds of, total 10(11) of immune cells are regulated by receiving
      appropriate signals in appropriate places. We have been attempting to understand
      immune system by revealing spatiotemporal regulation of immune cells at the whole
      body level by "Visualization of immune response in vivo". Photoconvertible
      protein, "Kaede"-Tg mice allowed us to monitor cell-replacement and cell-movement
      in the whole body by marking cells with color of Kaede from green to red with
      exposure to violet light. It is applicable to small cell number populations in
      both lymphoid organs and also peripheral tissues under both normal and
      pathophysiological conditions. By using this system, we have demonstrated novel
      findings that "Naive CD4(+) T cell recirculation is an active process that they
      recirculate through lymphoid organs to seek limited niche for interacting with
      endogenous antigens and upregulate their function." and "Activated regulatory T
      cells emigrating from cutaneous immune response is responsible for termination of
      immune reponse." I will introduce these new tools of us and would like to discuss
      what is needed to understand immune system in the entire body.

PMID- 23546588
TI  - [A pathophysiological role of cytochrome p450 involved in production of reactive
      oxygen species].
AB  - Dysregulation of the production of reactive oxygen species (ROS) determines
      cellular function. Cytochrome P450s (CYPs) regulates ROS production and
      contributes to the process of cell death. This review summarizes our recent
      findings, focusing on the involvement of CYPs in pathophysiology induced by ROS.
      1. Quinone toxicity in hepatocytes: CYPs require electrons supplied from NADPH
      cytochrome P450 reductase (NPR) during the process of metabolism. NPR also
      provides electrons to quinone compounds, which compete with CYPs over electrons.
      Inhibition of CYPs shifts NPR's electron flow more to quinones, which accelerates
      the redox cycle to enhance ROS production and quinone toxicity. 2. Myocardial
      ischemia-reperfusion injury: Reperfusion of blood flow after coronary artery
      occlusion induces cell damage, as evident by the extension of myocardial infarct
      size and caspase-independent cell apoptosis. CYP2C6 appears to be a source for
      ROS production, since sulfaphenazole, a selective inhibitor of CYP2C6, reduces
      this damage. ROS produced by CYP2C6 during the reperfusion causes translational
      activation of Noxa and BimEL, as well as the suppression of caspase activation,
      resulting in caspase-independent apoptosis. 3. Primary hepatocyte apoptosis:
      Inhibition of catalase and glutathione peroxidase increases intracellular ROS and
      elicits caspase-independent hepatocyte apoptosis. SKF-525A, a pan-CYP inhibitor,
      suppresses these ROS increases and hepatocyte apoptosis. Increased ROS activates
      ERK and AP-1 by inhibition of tyrosine phosphatase, and inhibits BimEL
      degradation by proteasome. These results in the accumulation of mitochondrial
      BimEL, which then induces the release of cytochrome c and endonuclease G (EndoG).
      Increased ROS also keeps caspases inactivated. As a result, EndoG executes
      nucleosomal DNA fragmentation.

PMID- 23546589
TI  - [Transporter-mediated regulation of pharmacokinetics of lifestyle-related
      substances].
AB  - Recent studies revealed the importance of transporters in the behaviors of small
      molecules in the body. In mammals, the presence of a lot of transporters has been
      suggested, such as ATP-binding cassette (ABC) transporters and solute ligand
      carrier (SLC) transporters, some of which are clarified to be causative genes for
      various kinds of genetic disorders. In addition, a lot of transporters are known
      to mediate cellular import or export of drugs, to contribute to the
      pharmacokinetics of substrate drugs and to be involved in the interindividual
      differences of drug responses. In this review, I introduce our recent work on the
      transporter-mediated regulation of pharmacokinetics of lifestyle-related
      substances, such as cholesterol and urate.

PMID- 23546590
TI  - [Causes of emergency hospitalization of elderly diabetic patients].
AB  - In recent years there has been a rise in the number of diabetic patients in
      Japan, with the increase in elderly diabetic patients becoming a serious problem.
      This study looked at 488 elderly type 2 diabetes patients who were admitted as
      emergency cases to the Department of Internal Medicine, JA Yoshida General
      Hospital, Akitakada City, Japan. All patients were classified by age into three
      groups: <70, 70-80 and >80. The most common cause of emergency hospitalization in
      each of the three age groups was infection. This was significantly higher in the
      >80 group in comparison with<70 (p<0.05). The most common infection among the
      three groups was respiratory infection, followed by urinary tract infection. The
      number of emergency hospitalization cases due to hypoglycemia was much higher in
      the over 80 group, particularly in comparison with<70-80 (p<0.05). The incidence
      of hypoglycemia in our patients could be explained mainly by reduced energy
      intake. Most cases were treated with oral administration of hypoglycemic drugs.
      As elderly diabetic patients have a number of underlying illnesses that are prone
      to aggravation and may lead to unfavorable prognosis, early medical examination
      and disease detection are considered to be important. Pharmacists are required to
      educate patients, home-visit nursing care personnel on sick-day rule, and provide
      diabetes care.

PMID- 23546591
TI  - Preclinical evaluation of combined TKI-258 and RAD001 in hepatocellular
      carcinoma.
AB  - PURPOSE: RAD001 targets at the mammalian target of rapamycin (mTOR), while TKI
      258 is a potent tyrosine kinase inhibitor targeting at fibroblast growth factor
      receptor, vascular endothelial growth factor receptor, platelet-derived growth
      factor receptor and c-kit. We aim to study the activity of combined RAD001 and
      TKI-258 in cell lines and xenograft model of hepatocellular carcinoma (HCC), with
      reference to the parallel and upstream pathways of Akt-mTOR axis. METHODS: A
      panel of 4 human HCC cell lines HepG2, Hep3B, PLC/PRF/5 and Huh7 and the Hep3B
      derived xenograft were treated with TKI-258 or/and RAD001, respectively. Related
      mechanistic studies (including apoptosis and angiogenesis) were conducted.
      RESULTS: There was an enhanced increase in suppression of cell proliferation with
      combined TKI-258 and RAD001 compared with either drug alone. The combination
      could significantly suppress the phosphorylation of mTOR, MEK1/2 and p38 MAPK.
      Although the addition of the TKI258 only slightly suppressed the phosphorylation
      of AKT induced by RAD001, the pi-mTOR and its downstream signaling pathways
      including pi-p70S6K, pi-S6 and pi-4EBP1 were lowered in the combination. In Hep3B
      derived xenograft, TKI-258 and RAD001 had shown an enhanced inhibition of tumor
      growth without impact on the weight of animals. There was a reduction in
      microvessel density in the xenograft with the combination, which indicated an
      enhanced inhibition on angiogenesis. Pro-caspases-3 and PARP cleavage were
      slightly detected at 48 h after treatment, suggesting that the combination mainly
      increased the cytostatic arrest ability. CONCLUSIONS: The combination of RAD001
      and TKI-258 was active in HCC via inhibition of both mTOR-mediated signaling and
      its parallel pathways.

PMID- 23546592
TI  - Diversity of sequences and expression patterns among alleles of a sugarcane
      loading stem gene.
AB  - Modern sugarcane cultivars are highly polyploid and aneuploid hybrids, which are
      propagated as clones. Their complex genome structure comprises 100-130
      chromosomes and 10-13 hom(e)ologous copies of most loci. There is preliminary
      evidence of very high heterozygosity, with implications for genetic improvement
      approaches ranging from marker-assisted selection to transgenics. Here, we report
      that sugarcane cultivar Q200 has at least nine alleles at the Loading Stem Gene
      (ScLSG) locus. Exon-intron structure is identical and the predicted protein
      products show at least 92 % identity, across sugarcane alleles and the Sorghum
      homologue Sb07g027880. There is substantial variation in the 5' UTR and promoter
      regions including numerous allele-specific nucleotide polymorphisms, insertions
      and deletions. We developed an allele-specific qRT-PCR method to undertake the
      first compelling test of allele-specific expression in polyploid sugarcane. Seven
      alleles distinguished by this method all showed peak expression in the sucrose
      loading zone of the stem, but there was apparent variability in expression
      patterns across other tissues. The ScLSG2 and ScLSG5 alleles appear promising for
      specificity of expression in stems, relative to leaf, meristem, emerging shoot
      and root tissues. Within the stem, there was activity in parenchyma, vascular and
      rind tissues. This expression pattern is of interest in basic research and
      biotechnology aimed at enhanced sucrose content, engineering value-added
      products, and manipulation of stem biomass composition. 

PMID- 23546593
TI  - Expression and significance of PTEN and miR-92 in hepatocellular carcinoma.
AB  - The aim of this study was to investigate the correlation between the expression
      levels of the tumor suppressor gene phosphatase and tensin homolog (PTEN) and the
      microRNA (miRNA) miR-92 in hepatocellular carcinoma (HCC) and paracancerous
      tissue. Immunohistochemistry [streptavidin-peroxidase (SP)] and quantitative
      reverse transcriptase-polymerase chain reaction (qRT-PCR) were used to detect the
      expression of PTEN and miR-92 in 15 cases of HCC and the corresponding
      paracancerous tissues. The correlation between PTEN and miR-92 was analyzed. The
      expression of PTEN mRNA and protein was significantly lower in HCC compared with
      that in paracancerous tissues (P<0.05). miR-92 showed the opposite expression
      pattern (P<0.05). Additionally, the mRNA levels of PTEN and miR-92 showed a
      significantly negative correlation with each other (r=-0.858, P<0.05). In
      conclusion, PTEN and miR-92 have different roles in the development of HCC. The
      combined detection of PTEN and miR-92 may provide critical clinical evidence for
      the early diagnosis and prognosis of HCC.

PMID- 23546594
TI  - Suppression of RND3 activity by AES downregulation promotes cancer cell
      proliferation and invasion.
AB  - Amino-terminal enhancer of split (AES) is a member of the Groucho/TLE family.
      Although it has no DNA-binding site, AES can regulate transcriptional activity by
      interacting with transcriptional factors. Emerging evidence indicates that AES
      may play an important role in tumor metastasis, but the molecular mechanism is
      still poorly understood. In this study, we found that knockdown of AES by RNA
      interference (RNAi) downregulated RND3 expression at the mRNA and protein levels
      in MDA-MB-231 and HepG2, two cancer cell lines. Furthermore, luciferase assays
      showed that overexpression of AES significantly enhanced RND3 promoter activity.
      Moreover, inhibition of AES both in MDA-MB-231 and HepG2 cells by RNAi
      significantly promoted cell proliferation, cell cycle progression and invasion,
      consistent with the effects of RNAi-mediated RND3 knockdown in these cells. For
      the first time, data are presented showing that alteration of the malignant
      behavior of cancer cells by AES is related to RND3 regulation, and these findings
      also provide new insights into the mechanism of AES action in regulating tumor
      malignancy.

PMID- 23546595
TI  - Identification and verification of transthyretin as a potential biomarker for
      pancreatic ductal adenocarcinoma.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal
      cancers worldwide and is difficult to detect at its early stages when treatment
      is most effective. Therefore, we performed a comparative proteomic study to
      identify new biomarkers for the detection of PDAC. METHODS: Serum samples from
      patients with PDAC, chronic pancreatitis and normal controls were compared using
      two-dimensional difference gel electrophoresis (2D-DIGE). Differentially
      expressed separated proteins were subsequently identified by matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS).
      Then, transthyretin (TTR), one of the differentially expressed proteins, was
      validated through real-time PCR, western blot and immunohistochemistry. Finally,
      enzyme-linked immunosorbent assays (ELISA) were employed to confirm the levels of
      transthyretin in the sera. RESULTS: A total of 21 protein spots showed greater
      than 1.5-fold changes in expression level in the sera from PDAC patients compared
      with the normal controls. Among the identified proteins, validation experiments
      verified the differential expression of transthyretin in PDAC tissue, confirming
      the proteomic data showing that transthyretin was significantly elevated in
      patients with PDAC. The ELISA results revealed that the sensitivity and
      specificity for TTR and CA19-9 in distinguishing PDAC patients from normal
      individuals were 90.5, 47.6, 66.7 and 85.7 %, respectively, and 81.0 and 85.7 %
      for their combination. CONCLUSIONS: These results suggest that the level of
      transthyretin is elevated in patients with PDAC. In combination with CA19-9,
      transthyretin may provide additional information for the detection of PDAC and
      should be further investigated.

PMID- 23546596
TI  - The promotional effect of Sn-beta zeolites on platinum for the selective
      hydrogenation of alpha,beta-unsaturated aldehydes.
AB  - Pt impregnated on a Sn-beta catalyst results in a very promising catalyst for the
      selective hydrogenation of alpha,beta-unsaturated aldehydes, compared to the PtSn
      co-impregnated beta catalysts. Framework tin ions in the Sn-beta sample stabilize
      the nucleation of platinum nanoparticles inside the zeolite channel. These Pt(0)
      Sn(4+) sites, which are only observed in the Pt/Sn-beta catalyst, have been shown
      to strongly activate the carbonyl group enhancing the hydrogenation rate of the
      C=O bond.

PMID- 23546597
TI  - Mentorship moves science forward.

PMID- 23546598
TI  - Controlled growth of Ni nanocrystals on SrTiO(3) and their application in the
      catalytic synthesis of carbon nanotubes.
AB  - Truncated pyramid-shaped Ni nanocrystals were epitaxially grown on SrTiO(3)(001)
      surfaces and characterised by scanning tunneling microscopy (STM). These
      nanocrystals were shown to be catalytically active for the synthesis of carbon
      nanotubes (CNTs). The narrow size distribution of the Ni nanocrystals results in
      a similar narrow distribution of CNT diameters.

PMID- 23546599
TI  - PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary
      bladder of female rat.
AB  - Acute bladder distension causes various morphologic and functional changes, in
      part through altered gene expression. We aimed to investigate the physiologic
      role of PTHrP, which is up-regulated in an acute bladder distension model in
      female rats. In the control Empty group, bladders were kept empty for 6 hours,
      and in the Distension group, bladders were kept distended for 3 hours after an
      artificial storing-voiding cycle for 3 hours. In the Distention group bladder, up
      regulation of transcripts was noted for 3 genes reported to be up-regulated by
      stretch in the cultured bladder smooth muscle cells in vitro. Further
      transcriptome analysis by microarray identified PTHrP as the 22nd highest gene up
      regulated in Distension group bladder, among more than 27,000 genes. Localization
      of PTHrP and its functional receptor, PTH/PTHrP receptor 1 (PTH1R), were analyzed
      in the untreated rat bladders and cultured bladder cells using real-time RT-PCR
      and immunoblotting, which revealed that PTH1R and PTHrP were more predominantly
      expressed in smooth muscle than in urothelium. Exogenous PTHrP peptide (1-34)
      increased intracellular cAMP level in cultured bladder smooth muscle cells. In
      organ bath study using bladder strips, the PTHrP peptide caused a marked
      reduction in the amplitude of spontaneous contraction but caused only modest
      suppression for carbachol-induced contraction. In in vivo functional study by
      cystometrogram, the PTHrP peptide decreased voiding pressure and increased
      bladder compliance. Thus, PTHrP is a potent endogenous relaxant of bladder
      contraction, and autocrine or paracrine mechanism of the PTHrP-PTH1R axis is a
      physiologically relevant pathway functioning in the bladder.

PMID- 23546601
TI  - Estrogen receptor-alpha variant, ER-alpha36, is involved in tamoxifen resistance
      and estrogen hypersensitivity.
AB  - Antiestrogens such as tamoxifen (TAM) provided a successful treatment for
      estrogen receptor (ER)-positive breast cancer for the past four decades. However,
      most breast tumors are eventually resistant to TAM therapy. The molecular
      mechanisms underlying TAM resistance have not been well established. Recently, we
      reported that breast cancer patients with tumors expressing high concentrations
      of ER-alpha36, a variant of ER-alpha, benefited less from TAM therapy than those
      with low concentrations of ER-alpha36, suggesting that increased ER-alpha36
      concentration is one of the underlying mechanisms of TAM resistance. Here, we
      investigated the function and underlying mechanism of ER-alpha36 in TAM
      resistance. We found that TAM increased ER-alpha36 concentrations, and TAM
      resistant MCF7 cells expressed high concentrations of ER-alpha36. In addition,
      MCF7 cells with forced expression of recombinant ER-alpha36 and H3396 cells
      expressing high concentrations of endogenous ER-alpha36 were resistant to TAM. ER
      alpha36 down-regulation in TAM-resistant cells with the short hairpinRNA method
      restored TAM sensitivity. We also found that TAM acted as a potent agonist by
      activating phosphorylation of the AKT kinase in ER-alpha36-expressing cells.
      Finally, we found that cells with high concentration of ER-alpha36 protein were
      hypersensitive to estrogen, activating ERK phosphorylation at picomolar range.
      Our results thus demonstrated that elevated ER-alpha36 concentration is one of
      the mechanisms by which ER-positive breast cancer cells escape TAM therapy and
      provided a rational to develop novel therapeutic approaches for TAM-resistant
      patients by targeting ER-alpha36.

PMID- 23546600
TI  - A 5'-flanking region of gonadotropin-regulated testicular RNA helicase
      (GRTH/DDX25) gene directs its cell-specific androgen-regulated gene expression in
      testicular germ cells.
AB  - Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is a
      posttranscriptional regulator of genes that are essential for spermatid
      elongation and completion of spermatogenesis. It also prevents Leydig cells (LCs)
      from gonadotropin overstimulation of androgen production. In transgenic (Tg) mice
      carrying deletions of the GRTH 5'-flanking regions, we previously demonstrated
      that the -1085 bp to ATG contains the elements for basal and androgen-induced LC
      specific expression. No expression in germ cells (GCs) was found with sequences
      extended up to -3.6 kb. To define regulatory regions of GRTH required for
      expression in GC, Tg mice were generated with 5'-flanking sequence 6.4 kb (6.4 Kb
      Tg) and/or deletion using green fluorescent protein (GFP) as reporter gene in the
      present study. GFP was expressed in all lines. Immunohistochemistry analysis
      showed that 6.4 Kb-Tg directed GFP expression in both GCs and LCs. Deletion of
      the sequence -205 bp to -3.6 kb (6.4 Kb/del-Tg) directs GFP expression only in
      meiotic and haploid GCs. This indicated that the distal region -6.4 kb/-3.6 kb is
      required for GRTH cell-specific expression in GC. Also, it inhibits the
      expression of GRTH in LC directed by the 205-bp promoter, an effect that is
      neutralized by the -3.6-kb/-205-bp sequence. Androgen receptor antagonist,
      flutamide treatment prevents GFP/GRTH expression in Tg lines, demonstrating in
      vivo direct and indirect effects of endogenous androgen on LCs and GCs,
      respectively. Our studies have generated and characterized Tg lines that can be
      used to define requirements for cell-specific expression of the GRTH gene and to
      further advance our knowledge on the regulation of GRTH by androgen in GCs.

PMID- 23546602
TI  - 17beta-estradiol activates glucose uptake via GLUT4 translocation and PI3K/Akt
      signaling pathway in MCF-7 cells.
AB  - The relationship between estrogen and some types of breast cancer has been
      clearly established. However, although several studies have demonstrated the
      relationship between estrogen and glucose uptake via phosphatidylinositol 3
      kinase (PI3K)/Akt in other tissues, not too much is known about the possible
      cross talk between them for development and maintenance of breast cancer. This
      study was designed to test the rapid effects of 17beta-estradiol (E2) or its
      membrane-impermeable form conjugated with BSA (E2BSA) on glucose uptake in a
      positive estrogen receptor (ER) breast cancer cell line, through the possible
      relationship between key components of the PI3K/Akt signaling pathway and acute
      steroid treatment. MCF-7 human breast cancer cells were cultured in standard
      conditions. Then 10 nM E2 or E2BSA conjugated were administered before obtaining
      the cell lysates. To study the glucose uptake, the glucose fluorescent analog 2
      [N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose was used. We
      report an ER-dependent activation of some of the key steps of the PI3K/Akt
      signaling pathway cascade that leads cells to improve some mechanisms that
      finally increase glucose uptake capacity. Our data suggest that both E2 and E2BSA
      enhance the entrance of the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa
      1,3-diazol-4-yl)amino]-2-deoxy-d-glucose, and also activates PI3K/Akt signaling
      pathway, leading to translocation of glucose transporter 4 to the plasma membrane
      in an ERalpha-dependent manner. E2 enhances ER-dependent rapid signaling
      triggered, partially in the plasma membrane, allowing ERalpha-positive MCF-7
      breast cancer cells to increase glucose uptake, which could be essential to meet
      the energy demands of the high rate of proliferation.

PMID- 23546603
TI  - Excess androgens in utero alters fetal testis development.
AB  - Prenatal androgenization induces a polycystic ovary syndrome-like phenotype in
      adult female offspring, which is associated with alterations that can be detected
      in the fetal ovary, suggesting gestational origins of this condition. We
      therefore investigated whether increased prenatal androgen exposure also altered
      testicular development using ovine animal models. Biweekly maternal testosterone
      propionate (TP; 100 mg) from day 62 to day 70/day 90 of gestation altered male
      developmental trajectory. In male fetuses serum LH was decreased (P < .01), and
      testicular STAR, CYP11, and CYP17 abundance were reduced. Coincident with this,
      basal testicular T synthesis was decreased in vitro (P < .001). Leydig cell
      distribution was severely perturbed in all testes prenatally exposed to TP (P <
      .001). To examine the contribution of estrogens, fetuses were injected with TP
      (20 mg), the potent estrogen agonist, diethylstilbestrol (DES; 20 mg), or vehicle
      control at day 62 and day 82 and assessed at day 90. The effects of fetal
      (direct) TP treatment, but not DES, paralleled maternal (indirect) TP exposure,
      supporting a direct androgen effect. Cessation of maternal androgenization at day
      102 returned Leydig cell distribution to normal but increased basal T output, at
      day 112, demonstrating Leydig cell developmental plasticity. Earlier maternal
      androgen exposure from day 30 similarly influenced Leydig cell development at day
      90 but additionally affected the expression of Sertoli and germ cell markers. We
      show in this study that increased prenatal androgen exposure alters development
      and function of Leydig cells at a time when androgen production is paramount for
      male development. This supports the concept that gestational antecedents
      associated with polycystic ovary syndrome may have effects on the male fetus.

PMID- 23546605
TI  - Ovarian expression of insulin-like peptide 3 (INSL3) and its receptor (RXFP2)
      during development of bovine antral follicles and corpora lutea and measurement
      of circulating INSL3 levels during synchronized estrous cycles.
AB  - Insulin-like peptide 3 (INSL3), a major product of testicular Leydig cells, is
      also expressed by the ovary, but its functional role remains poorly understood.
      Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna
      cell (TIC) and granulosa cell compartments of developing bovine antral follicles
      and in corpora lutea (CL). INSL3 and RXFP2 mRNA levels were much higher in TIC
      than granulosa cell and increased progressively during follicle maturation with
      INSL3 peaking in large (11-18 mm) estrogen-active follicles and RXFP2 peaking in
      9- to 10-mm follicles before declining in larger (11-18 mm) follicles. Expression
      of both INSL3 and RXFP2 in CL was much lower than in TIC. In situ hybridization
      and immunohistochemistry confirmed abundant expression of INSL3 mRNA and protein
      in TIC. These observations indicate follicular TIC rather than CL as the primary
      site of both INSL3 production and action, implying a predominantly
      autocrine/paracrine role in TIC. To corroborate the above findings, we showed
      that in vitro exposure of TIC to a luteinizing concentration of LH greatly
      attenuated expression of both INSL3 and its receptor while increasing
      progesterone secretion and expression of STAR and CYP11A1. Moreover, in vivo, a
      significant cyclic variation in plasma INSL3 was observed during synchronized
      estrous cycles. INSL3 and estradiol-17beta followed a similar pattern, both
      increasing after luteolysis, before falling sharply after the LH surge. Thus,
      theca-derived INSL3, likely from the dominant preovulatory follicle, is
      detectable in peripheral blood of cattle, and expression is down-regulated during
      luteinization induced by the preovulatory LH surge. Collectively, these findings
      underscore the likely role of INSL3 as an important intrafollicular modulator of
      TIC function/steroidogenesis, while raising doubts about its potential
      contribution to CL function.

PMID- 23546604
TI  - Palladin is a regulator of actin filament bundles at the ectoplasmic
      specialization in adult rat testes.
AB  - In rat testes, the ectoplasmic specialization (ES) at the Sertoli-Sertoli and
      Sertoli-spermatid interface known as the basal ES at the blood-testis barrier and
      the apical ES in the adluminal compartment, respectively, is a testis-specific
      adherens junction. The remarkable ultrastructural feature of the ES is the actin
      filament bundles that sandwiched in between the cisternae of endoplasmic
      reticulum and apposing plasma membranes. Although these actin filament bundles
      undergo extensive reorganization to switch between their bundled and debundled
      state to facilitate blood-testis barrier restructuring and spermatid
      adhesion/transport, the regulatory molecules underlying these events remain
      unknown. Herein we report findings of an actin filament cross-linking/bundling
      protein palladin, which displayed restrictive spatiotemporal expression at the
      apical and the basal ES during the epithelial cycle. Palladin structurally
      interacted and colocalized with Eps8 (epidermal growth factor receptor pathway
      substrate 8, an actin barbed end capping and bundling protein) and Arp3 (actin
      related protein 3, which together with Arp2 form the Arp2/3 complex to induce
      branched actin nucleation, converting bundled actin filaments to an
      unbundled/branched network), illustrating its role in regulating actin filament
      bundle dynamics at the ES. A knockdown of palladin in Sertoli cells in vitro with
      an established tight junction (TJ)-permeability barrier was found to disrupt the
      TJ function, which was associated with a disorganization of actin filaments that
      affected protein distribution at the TJ. Its knockdown in vivo also perturbed F
      actin organization that led to a loss of spermatid polarity and adhesion, causing
      defects in spermatid transport and spermiation. In summary, palladin is an actin
      filament regulator at the ES.

PMID- 23546606
TI  - Importance of cysteine residues in the thyroid hormone transporter MCT8.
AB  - The thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) is
      crucial for brain development as demonstrated by the severe psychomotor
      retardation in patients with MCT8 mutations. MCT8 contains 10 residues of the
      reactive amino acid cysteine (Cys) whose functional roles were studied using the
      Cys-specific reagent p-chloromercurybenzenesulfonate (pCMBS) and by site-directed
      mutagenesis. Pretreatment of JEG3 cells with pCMBS resulted in a dose- and time
      dependent decrease of subsequent T3 uptake. Pretreatment with dithiothreitol did
      not affect TH transport or its inhibition by pCMBS. However, pCMBS inhibition of
      MCT8 was reversed by dithiothreitol. Inhibition of MCT8 by pCMBS was prevented in
      the presence of T3. The single and double mutation of C481A and C497A did not
      affect T3 transport, but the single mutants were less sensitive and the double
      mutant was completely insensitive to pCMBS. Similar effects on MCT8 were obtained
      using HgCl2 instead of pCMBS. In conclusion, we have identified Cys481 and Cys497
      in MCT8 as the residues modified by pCMBS or HgCl2. These residues are probably
      located at or near the substrate-recognition site in MCT8. It remains to be
      investigated whether MCT8 function is regulated by modification of these Cys
      residues under pathophysiological conditions.

PMID- 23546607
TI  - Use of glucocorticoids and risk of venous thromboembolism: a nationwide
      population-based case-control study.
AB  - IMPORTANCE: Excess endogenous cortisol has been linked to venous thromboembolism
      (VTE) risk, but whether this relationship applies to exogenous glucocorticoids
      remains uncertain. Because the prevalence of glucocorticoid use and the incidence
      of VTE are high, an increased risk of VTE associated with glucocorticoid use
      would have important implications. BACKGROUND: To examine the association between
      glucocorticoid use and VTE. DESIGN: Population-based case-control study using
      nationwide databases. SETTING: Denmark (population 5.6 million). PARTICIPANTS: We
      identified 38,765 VTE cases diagnosed from January 1, 2005, through December 31,
      2011, and 387,650 population controls included through risk-set sampling and
      matched by birth year and sex. The VTE diagnosis date for the case was the index
      date for cases and matched controls. EXPOSURE: We classified individuals who
      filled their most recent glucocorticoid prescription 90 days or less, 91 to 365
      days, and more than 365 days before the index date as present, recent, and former
      users, respectively. Present users were subdivided into new (first-ever
      prescription 90 days or less before the index date) and continuing users
      (others). MAIN OUTCOMES AND MEASURES: We used conditional logistic regression
      adjusted for VTE risk factors to estimate incidence rate ratios (IRRs) and 95%
      CIs for glucocorticoid users vs nonusers. RESULTS: Systemic glucocorticoids
      increased VTE risk among present (adjusted IRR, 2.31; 95% CI, 2.18-2.45), new
      (3.06; 2.77-3.38), continuing (2.02; 1.88-2.17), and recent (1.18; 1.10-1.26)
      users but not among former users (0.94; 0.90-0.99). The adjusted IRR increased
      from 1.00 (95% CI, 0.93-1.07) for a prednisolone-equivalent cumulative dose of 10
      mg or less to 1.98 (1.78-2.20) for more than 1000 to 2000 mg, and to 1.60 (1.49
      1.71) for doses higher than 2000 mg. New use of inhaled (adjusted IRR, 2.21; 95%
      CI, 1.72-2.86) and intestinal-acting (2.17; 1.27-3.71) glucocorticoids also
      increased VTE risk. CONCLUSIONS AND RELEVANCE: The risk of VTE is increased among
      glucocorticoid users. Although residual confounding may partly explain this
      finding, we consider a biological mechanism likely because the association
      followed a clear temporal gradient, persisted after adjustment for indicators of
      severity of underlying disease, and existed also for noninflammatory conditions.
      Hence, our observations merit clinical attention.

PMID- 23546608
TI  - Late peritoneal leakage.

PMID- 23546609
TI  - Androgen deprivation therapy and the risk of colorectal cancer in patients with
      prostate cancer.
AB  - PURPOSE: Androgens are known to play an important protective role on colorectal
      carcinogenesis, and thus the objective of this study was to determine whether
      androgen deprivation therapy (ADT) is associated with an increased risk of
      incident colorectal cancer in patients with prostate cancer. METHODS: We
      conducted a population-based cohort study within the UK General Practice Research
      Database population which included all patients newly diagnosed with prostate
      cancer between 1 January 1988 and 31 December 2008, followed until 31 December
      2009. Time-dependent Cox proportional hazards models were used to estimate hazard
      ratios (HRs) and 95 % confidence intervals (CIs) of incident primary colorectal
      cancer associated with the use of ADT. Secondary analyses considered cumulative
      duration of use and specific ADTs. RESULTS: The cohort included a total of 21,503
      patients, of whom 184 were diagnosed with colorectal cancer during a mean (SD)
      follow-up 4.0 (3.0) years (rate 2.4/1,000 person-years). Overall, use of ADT was
      not associated with an increased risk of colorectal cancer (HR 0.99, 95 % CI 0.73
      1.35). Similarly, no association was observed in terms of duration use, although
      this secondary analysis may have been limited by statistical power. With respect
      to specific ADTs, bilateral orchiectomy was the only therapy associated with an
      increased risk of colorectal cancer (HR 2.50, 95 % CI 1.13-5.52). CONCLUSION:
      Overall, the use of ADT is not associated with an increased risk of incident
      colorectal cancer. The increased risk observed with bilateral orchiectomy may
      possibly be due to the prolonged androgen suppression of this therapy.

PMID- 23546610
TI  - Body fat and risk of colorectal cancer among postmenopausal women.
AB  - Studies of the relationship between anthropometric indices of obesity and
      colorectal cancer risk in women have shown only weak and inconsistent
      associations. Given the limitations of such indices, we used dual-energy X-ray
      absorptiometry (DXA)-derived measures of body fat obtained in the Women's Health
      Initiative to examine the association between body fat and risk of incident
      colorectal cancer. We compared these risk estimates with those obtained using
      conventional anthropometric measurements (body mass index and waist
      circumference). After exclusions, the study population consisted of 11,124
      postmenopausal women with DXA measurements at baseline and no history of
      colorectal cancer. After a median follow-up period of 12.9 years, 169 incident
      colorectal cancer cases were ascertained. Cox's proportional hazards models were
      used to estimate hazard ratios and 95 % confidence intervals for the exposures of
      interest. Neither DXA-derived body fat measures nor anthropometric measures
      showed significant associations with risk. In view of the limited number of
      cases, we cannot rule out the existence of weak associations of these measures
      with risk of colorectal cancer.

PMID- 23546611
TI  - Coffee consumption and risk of colorectal cancer: a dose-response analysis of
      observational studies.
AB  - Coffee consumption has been linked to risk of colorectal cancer theoretically,
      but the findings were conflicting from observational studies. Results from the
      recent meta-analysis suggested a moderate favorable effect of coffee consumption
      on colorectal cancer risk, especially for colon cancer. However, the
      relationship, if exists, between coffee consumption and colorectal cancer risk is
      unclear. Thus, the dose-response relationship was assessed by restricted cubic
      spline model and multivariate random-effect meta-regression. The results
      suggested that a significant association was found between coffee consumption and
      decreased risk of colorectal and colon cancer among subjects consuming >=4 cups
      of coffee per day. A potential nonlinear relationship should be assessed before
      assuming a linear relationship.

PMID- 23546612
TI  - Relationship of thyroid hormone levels and cardiovascular events in patients with
      type 2 diabetes.
AB  - Alterations in thyroid hormone levels are found associated with inflammation in
      patients with non-thyroidal illness (NTIS) and are common in patients with type 2
      diabetes mellitus (T2DM). Inflammation has also been linked with development of
      cardiovascular events (CVE) in T2DM. Our objective was to assess whether thyroid
      hormone abnormalities typical of NTIS in patients with T2DM are related to
      inflammation and CVE. This was a cross-sectional study of 140 subjects; 70 with
      T2DM and 70 as a control group paired by age, sex and body mass index (BMI). We
      recorded age, sex, BMI, waist/hip ratio, diabetes duration, HbA1c, CVE history,
      serum amyloid A (SAA), TSH, total (T) and free (F) T4 and T3, reverse T3 (rT3)
      and TT3/rT3 ratio. Patients with T2DM had lower levels of TT4 (p = 0.012), TT3 (p
      < 0.001), FT3 (p < 0.001) and TT3/rT3 (p = 0.002). They also showed higher FT4 (p
      < 0.001) and similar TSH levels (p = 0.627) compared to the control group. SAA
      levels correlated positively with rT3 (r = 0.45; p < 0.001) and inversely with
      TT3/rT3 (r = -0.38; p = 0.001). Patients with T2DM and history of CVE had higher
      rT3 (p = 0.006) and lower TT3/rT3 (p = 0.002), along with higher SAA levels (p =
      0.002) than patients without this characteristic. Multiple logistic regression
      showed that factors independently associated with CVE were older age (OR = 1.159,
      95 % CI 1.011-1.329), male sex (OR = 4.391, 95 % CI 1.081-17.829) and higher
      TT3/rT3 (OR = 0.993, 95 % CI 0.987-0.999). We have confirmed the presence of NTIS
      in T2DM. We also showed that thyroid hormone abnormalities are associated to
      inflammatory activity and to CVE in these patients.

PMID- 23546613
TI  - Colorectal cancer association with metabolic syndrome and its components: a
      systematic review with meta-analysis.
AB  - We performed a systematic review and meta-analysis of the empirical evidence on
      the association of metabolic syndrome and its components with colorectal cancer
      incidence and mortality. A systematic literature search of multiple electronic
      databases was conducted and complemented by cross-referencing to identify studies
      published before 31 October 2012. Every included study was to report risk
      estimates with 95 % confidence intervals for the association between metabolic
      syndrome and colorectal cancer (incidence or mortality). Core items of identified
      studies were independently extracted by two reviewers, and results were
      summarized by standard methods of meta-analysis. We identified 17 studies, which
      reported on 49 data sets with 11,462 cancer cases. Metabolic syndrome was
      associated with an increased risk of colorectal cancer incidence and mortality in
      both men (RR: 1.33, 95 % CI 1.18-1.50, and 1.36, 1.25-1.48, respectively) and
      women (RR: 1.41, 1.18-1.70, and 1.16, 1.03-1.30, respectively). The risk
      estimates changed little depending on type of study (cohort vs non cohort),
      populations (US, Europe, Asia), cancer site (colon and rectum), or definition of
      the syndrome. The risk estimates for any single factor of the syndrome were
      significant for higher values of BMI/waist (RR: 1.19, 95 % CI 1.10-1.28),
      dysglycemia (RR: 1.29, 1.11-1.49), and higher blood pressure (RR: 1.09, 1.01
      1.18). Dysglycemia and/or higher BMI/waist explained most of the risk associated
      with metabolic syndrome. Metabolic syndrome is associated with an increased risk
      of colorectal cancer incidence and mortality in both sexes. The risk conveyed by
      the full syndrome is not superior to the sum of its parts.

PMID- 23546614
TI  - The consumption of n-3 polyunsaturated fatty acids differentially modulates gene
      expression of peroxisome proliferator-activated receptor alpha and gamma and
      hypoxia-inducible factor 1 alpha in subcutaneous adipose tissue of obese
      adolescents.
AB  - The aim of this study was to evaluate the effect of long-chain omega-3
      polyunsaturated fatty acid (n-3 PUFA) supplementation on metabolic state and gene
      expression in subcutaneous adipose tissues of obese adolescents. Obese
      adolescents (n = 26, 10 girls and 16 boys) aged 12.4 +/- 2.1 years were assigned
      to a 12-week regimen of n-3 PUFA intake. Five times per day, subjects received a
      food supplement consisting of eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA) (3 g per day, 944 mg EPA, and 2,088 mg DHA). Blood parameters were
      measured, and subcutaneous adipose tissue biopsies were analyzed to determine
      gene expression at baseline and after 12 weeks. Student's t test and the Wilcoxon
      signed-rank test were used to estimate differences in arithmetic means of pre-
      and post-dietary supplementation for various anthropometric, biochemical,
      clinical, and gene expression parameters. After 12 weeks, n-3 PUFA consumption
      was associated with decreased body mass index (29.7 +/- 4.6 vs. 27.8 +/- 4.4
      kg/m(2); P < 0.001), waist circumference (93.2 +/- 9.9 vs. 90.5 +/- 10.0 cm; P <
      0.003), hip circumference (102.9 +/- 10.9 vs. 101.1 +/- 10.9 cm; P < 0.014), and
      blood triglyceride levels (220.8 +/- 27.4 vs. 99.7 +/- 32.7 mg/dL; P < 0.001).
      Fatty acid supplementation/n3 PUFA supplementation was associated with a
      downregulated expression of the genes encoding PPARgamma and PGC-1alpha (P <
      0.001), and an upregulated expression of the genes encoding PPARalpha (P < 0.007)
      and SREBP1 (P < 0.021). The expressions of SOD2 (P < 0.04), CAT (P < 0.001), GPX3
      (P < 0.032) and HIF-1alpha protein also decreased. Our study demonstrated that n
      3 PUFA consumption and dietary restriction improved the anthropometric parameters
      and decreased the triglycerides levels of the adolescents, suggesting a reduction
      in hypoxia in subcutaneous adipose tissue.

PMID- 23546615
TI  - The impact of parental migration on the mental health of children left behind.
AB  - This study aims to examine the impact of parental international migration on the
      mental health of children left behind. Data for this paper were taken from the
      "Child Health and Migrant Parents in South-East Asia, Thailand, 2008" project. A
      total of 1,030 children (519 from emigrant parents and 511 from non-migrant
      parents) were covered. Data were collected from the caregivers of children using
      the Strength and Difficulties Questionnaire. Multivariate analyses were performed
      to determine the association between parental migration and the mental health
      status of children left behind. Several factors were significantly associated
      with children's mental health. Our study did not find any association between
      current parental migration status and mental health status of the children left
      behind. The study found, however, that mother's earlier migration history had a
      significant, independent association with mental health problems of the children
      left behind. Therefore, effective strategies to prevent such mental health
      problems among children are warranted. 

PMID- 23546616
TI  - Acculturation and associated effects on abused immigrant women's safety and
      mental functioning: results of entry data for a 7-year prospective study.
AB  - Intimate partner violence has negative effects on women's safety and wellbeing.
      When immigrant women are victimized the danger and poor health may intensify. The
      purpose was to determine the impact of acculturation on severity of violence,
      danger for murder, mental health functioning, and safety behaviors of abused
      immigrant women. Entry data of a 7-year prospective study of 106 abused immigrant
      women who were first time users of safe shelter or justice services is presented.
      The interview included the Severity of Violence Against Women Scale, Danger
      Assessment, Brief Symptom Inventory (BSI), Safety Behavior Checklist, and
      Acculturation for Hispanics instruments. A significant (p < 0.05) positive
      correlation between acculturation and safety behaviors and BSI scores was
      established. Higher acculturation scores were associated with significantly more
      practiced safety behaviors and higher levels of depression. Understanding the
      specific needs of abuse immigrant women associated with acculturation is
      imperative to develop interventions to interrupt abuse and promote safety and
      mental well-being. 

PMID- 23546617
TI  - Factors that influence parental decisions to participate in clinical research:
      consenters vs nonconsenters.
AB  - IMPORTANCE: A child's health, positive perceptions of the research team and
      consent process, and altruistic motives play significant roles in the decision
      making process for parents who consent for their child to enroll in clinical
      research. This study identified that nonconsenting parents were better educated,
      had private insurance, showed lower levels of altruism, and less understanding of
      study design. OBJECTIVE: To determine the factors associated with parental
      consent for their child's participation in a randomized, placebo-controlled
      trial. DESIGN: Cross-sectional survey conducted from July 2008 to May 2011. The
      survey was an ancillary study to the Randomized Intervention for Children with
      VesicoUreteral Reflux Study. SETTING: Seven children's hospitals participating in
      a randomized trial evaluating management of children with vesicoureteral reflux.
      PARTICIPANTS: Parents asked to provide consent for their child's participation in
      the randomized trial were invited to complete an anonymous online survey about
      factors influencing their decision. A total of 120 of the 271 (44%) invited
      completed the survey; 58 of 125 (46%) who had provided consent and 62 of 144
      (43%) who had declined consent completed the survey. MAIN OUTCOMES AND MEASURES:
      A 60-question survey examining child, parent, and study characteristics; parental
      perception of the study; understanding of the design; external influences; and
      decision-making process. RESULTS Having graduated from college and private health
      insurance were associated with a lower likelihood of providing consent. Parents
      who perceived the trial as having a low degree of risk, resulting in greater
      benefit to their child and other children, causing little interference with
      standard care, or exhibiting potential for enhanced care, or who perceived the
      researcher as professional were significantly more likely to consent to
      participate. Higher levels of understanding of the randomization process,
      blinding, and right to withdraw were significantly positively associated with
      consent to participate. CONCLUSIONS AND RELEVANCE Parents who declined consent
      had a relatively higher socioeconomic status, had more anxiety about their
      decision, and found it harder to make their decision compared with consenting
      parents, who had higher levels of trust and altruism, perceived the potential for
      enhanced care, reflected better understanding of randomization, and exhibited low
      decisional uncertainty. Consideration of the factors included in the conceptual
      model should enhance the quality of the informed consent process and improve
      participation in pediatric clinical trials.

PMID- 23546618
TI  - Overview of electron crystallography of membrane proteins: crystallization and
      screening strategies using negative stain electron microscopy.
AB  - Electron cryomicroscopy, or cryoEM, is an emerging technique for studying the
      three-dimensional structures of proteins and large macromolecular machines.
      Electron crystallography is a branch of cryoEM in which structures of proteins
      can be studied at resolutions that rival those achieved by X-ray crystallography.
      Electron crystallography employs two-dimensional crystals of a membrane protein
      embedded within a lipid bilayer. The key to a successful electron
      crystallographic experiment is the crystallization, or reconstitution, of the
      protein of interest. This unit describes ways in which protein can be expressed,
      purified, and reconstituted into well-ordered two-dimensional crystals. A
      protocol is also provided for negative stain electron microscopy as a tool for
      screening crystallization trials. When large and well-ordered crystals are
      obtained, the structures of both protein and its surrounding membrane can be
      determined to atomic resolution.

PMID- 23546619
TI  - Neutron scattering techniques and applications in structural biology.
AB  - Neutron scattering is exquisitely sensitive to the position, concentration, and
      dynamics of hydrogen atoms in materials and is a powerful tool for the
      characterization of structure-function and interfacial relationships in
      biological systems. Modern neutron scattering facilities offer access to a
      sophisticated, nondestructive suite of instruments for biophysical
      characterization that provides spatial and dynamic information spanning from
      Angstroms to microns and from picoseconds to microseconds, respectively.
      Applications in structural biology range from the atomic-resolution analysis of
      individual hydrogen atoms in enzymes through to meso- and macro-scale analysis of
      complex biological structures, membranes, and assemblies. The large difference in
      neutron scattering length between hydrogen and deuterium allows contrast
      variation experiments to be performed and enables H/D isotopic labeling to be
      used for selective and systematic analysis of the local structure, dynamics, and
      interactions of multi-component systems. This overview describes the available
      techniques and summarizes their practical application to the study of
      biomolecular systems.

PMID- 23546621
TI  - Protein microarrays for identification of novel extracellular protein-protein
      interactions.
AB  - Functional protein microarrays offer the capability for high-throughput protein
      interaction analysis and have long promised to be a powerful tool for
      understanding protein interactions at the proteome scale. Although popular
      techniques for protein-protein interaction mapping like yeast-two-hybrid and
      affinity-purification mass spectrometry have performed well for identifying
      intracellular protein-protein interactions, the study of interactions between
      extracellular proteins has remained challenging for these methods. Instead, the
      use of protein microarrays appears to be a robust and efficient method for the
      identification of interactions among the members of this class of protein. This
      unit describes methods for extracellular protein microarray production,
      screening, and analysis. A protocol is described for enhanced detection of low
      affinity interactions by generating multivalent complexes using Fc-fusion bait
      proteins and protein A microbeads, along with a statistical method for hit
      scoring and identification of nonspecific interactions.

PMID- 23546620
TI  - Overview of protein microarrays.
AB  - Protein microarray technology is an emerging field that provides a versatile
      platform for the characterization of hundreds of thousands of proteins in a
      highly parallel and high-throughput manner. Protein microarrays are composed of
      two major classes: analytical and functional. In addition, tissue or cell lysates
      can also be fractionated and spotted on a slide to form a reverse-phase protein
      microarray. Applications of protein microarrays, especially functional protein
      microarrays, have flourished over the past decade as the fabrication technology
      has matured. In this unit, advances in protein microarray technologies are
      reviewed, and then a series of examples are presented to illustrate the
      applications of analytical and functional protein microarrays in both basic and
      clinical research. Relevant areas of research include the detection of various
      binding properties of proteins, the study of protein post-translational
      modifications, the analysis of host-microbe interactions, profiling antibody
      specificity, and the identification of biomarkers in autoimmune diseases.

PMID- 23546622
TI  - Preparation of recombinant protein spotted arrays for proteome-wide
      identification of kinase targets.
AB  - Protein microarrays allow unique approaches for interrogating global protein
      interaction networks. Protein arrays can be divided into two categories: antibody
      arrays and functional protein arrays. Antibody arrays consist of various
      antibodies and are appropriate for profiling protein abundance and modifications.
      Functional full-length protein arrays employ full-length proteins with various
      post-translational modifications. A key advantage of the latter is rapid parallel
      processing of large number of proteins for studying highly controlled biochemical
      activities, protein-protein interactions, protein-nucleic acid interactions, and
      protein-small molecule interactions. This unit presents a protocol for
      constructing functional yeast protein microarrays for global kinase substrate
      identification. This approach enables the rapid determination of protein
      interaction networks in yeast on a proteome-wide level. The same methodology can
      be readily applied to higher eukaryotic systems with careful consideration of
      overexpression strategy.

PMID- 23546623
TI  - Detecting low-affinity extracellular protein interactions using protein
      microarrays.
AB  - Low-affinity extracellular protein interactions are critical for cellular
      recognition processes, but are not generally detected by methods that can be
      applied in a high-throughput manner. This unit describes a protein microarray
      platform that significantly improves the throughput of assays capable of
      detecting transient extracellular protein interactions. These methodological
      improvements now permit screening for novel extracellular receptor-ligand
      interactions on a genome-wide scale.

PMID- 23546624
TI  - Refolding of SDS-denatured proteins using amphipathic cosolvents and osmolytes.
AB  - Currently, the investigation of protein refolding processes involves several time
      consuming stages that require large amounts of protein and costly chemicals.
      Consequently, there is great interest in developing new approaches to the study
      of protein renaturation that are more technically and economically feasible. It
      has recently been reported that certain cosolvents are able to modulate the
      denaturing properties of sodium dodecyl sulfate (SDS) and induce the refolding of
      proteins. This unit presents a protocol to study and follow the renaturation of a
      protein (membrane or soluble) starting from a native or SDS-unfolded state using
      a variety of candidate cosolvents and osmolytes.

PMID- 23546625
TI  - Neurologically generated electric currents of myocytes are the most rapid
      stimulus for the capillary pumps, even preceding muscle contraction.

PMID- 23546626
TI  - Reply to Pancheva, Panchev, and Pancheva.

PMID- 23546627
TI  - Advances and challenges in screening traditional Chinese anti-aging materia
      medica.
AB  - To provide a better service for senior health care, we summarized screening
      studies of traditional Chinese anti-aging materia medica (TCAM). We collected and
      analyzed literature of TCAM screening studies using the lifespan test and animal
      models of aging from 1984 to 2012. We found 26 screening methods for TCAM, and
      153 single herbs or active ingredients of TCAM that have been screened out during
      the past 28 years. The cell lifespan test, the fruit fly lifespan test, and D
      galactose aging model were the most widely used and intensively studied screening
      methods. However, the method for establishing the D-galactose aging model needs
      to be standardized, and the D-galactose aging model cannot completely be a
      substitute for the normal aging mouse model. Great success has been achieved in
      screening studies in TCAM. To further improve screening studies in TCAM, we
      suggest that the D-galactose aging model be incorporated into the lifespan test
      in the New Drugs of Traditional Chinese Medicine Research Guide.

PMID- 23546628
TI  - A herbal formula for prevention of influenza-like syndrome: a double-blind
      randomized clinical trial.
AB  - OBJECTIVE: To investigate the efficacy of a herbal formula in the prevention of
      influenza or influenza-like syndrome among elderies residing in old-people's home
      in Hong Kong. The secondary objectives are to investigate the quality of life
      (QOL) and symptomology changes among the herbal users and to evaluate the safety
      of this formula. METHODS: In ten old people's home or community centres in New
      Territories, Hong Kong, 740 eligible subjects agreed to join the study and were
      randomized to receive a herbal formula or a placebo on alternate days over 8
      weeks. Among those 740 participants, 113 had provided blood samples for
      immunological assessments before and after the study drug. Assessments were done
      at 0, 4, 8 and 12 weeks. Participants were instructed to keep a daily record of
      body temperature and any symptoms as sore throat, myalgia, running nose or cough,
      and to report to assessor accordingly. Those reporting body temperature of 37.8 
      degrees C and above would be visited and a proper nasopharyngeal swab be taken
      for viral study. RESULTS: Seventy-two participants developed influenza-like
      symptoms but none of them was proven influenza in their nasopharyngeal swabs, 40
      of these patients belonged to the herbal group and 32 to the placebo group,
      without significant differences between groups. The difference on the changes in
      QOL between the two groups was not statistically significant. However, in the
      immunological study, the natural killer cell absolute count was significantly
      increased in the herbal group compared with the placebo group (463 +/- 253 vs 413
      +/- 198, P<0.05). CONCLUSIONS: The herbal preparation was not effective compared
      with placebo in the prevention of influenza-like syndrome. It was however safe
      and possibly supporting immunological responses.

PMID- 23546629
TI  - Effectiveness of Bufei Yishen Granule combined with acupoint sticking therapy on
      quality of life in patients with stable chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the efficacy of Bufei Yishen Granule BFYSG) combined with
      Shufei Tie acupoint sticking therapy on quality of life of patients with stable
      chronic obstructive pulmonary disease (COPD). METHODS: A multi-center, double
      blinded, double-dummy and randomized controlled method was adopted in this trial.
      A total of 244 patients were randomly assigned to a trial group and a control
      group according to the random number, each with 122 patients; treatment
      allocation occurred when the participants met the inclusion criteria and signed
      the informed consent form. In the trial group, patients were treated with BFYSG
      combined with "Shufei Tie" acupoint sticking therapy and sustained-release
      theophylline dummy, and in the control group patients were treated with oral
      sustained-release theophylline and BFYSG dummy combined with "Shufei Tie"
      acupoint sticking therapy dummy. The therapeutic course for two groups was 4
      months and the follow-up was 6 months. The frequency and duration of acute
      exacerbation calculated by adding up each frequency and duration of acute
      exacerbation in treatment and follow-up time respectively, the quality of life
      measured by the World Health Organization Quality of Life (WHOQOL)-BREF scale and
      adult COPD quality of life (COPD-QOL) scale were observed. RESULTS: Among the 244
      enrolled patients, 234 were screened for full analysis set (FAS); 221 were
      screened for per-protocol analysis set (PPS). After 4-month treatment and 6-month
      follow-up there were differences between the trial group and the control group in
      frequency of acute exacerbation (FAS: P=0.013; PPS: P=0.046); duration of acute
      exacerbation (FAS: P=0.005; PPS: P=0.006); scores of physiological, psychological
      and environment aspects of the WHOQOL-BREF questionnaire (FAS: P=0.002, P=0.006,
      P=0.000; PPS: P=0.00, P=0.001, P=0.000); scores of daily living ability, social
      activity, depression symptoms aspects of the COPD-QOL questionnaire (FAS:
      P=0.000, P=0.000, P=0.006; PPS: P=0.002, P=0.001, P=0.001). CONCLUSION: BFYSG
      combined with acupoint sticking therapy could improve the quality of life of
      patients with stable COPD.

PMID- 23546630
TI  - A comparison of brain activity between healthy subjects and stroke patients on
      fMRI by acupuncture stimulation.
AB  - OBJECTIVE: To investigate brain activity patterns during acupuncture in stroke
      patients, and to compare the result with normal subjects using functional
      magnetic resonance imaging (fMRI). METHODS: A total of 11 stroke patients with
      motor weakness and 10 healthy subjects were studied. fMRI was performed during
      acupuncture on the left side at points Quchi (LI11) and Zusanli (ST36). Data were
      analyzed using statistical parametric maps of brain activation induced by
      acupuncture stimulation. RESULTS: The results showed that stimulation of both
      LI11 and ST36 produced significantly different brain activation patterns between
      the two groups. The normal group showed a greater overall activation than the
      stroke group. In the normal group, parts of the frontal lobe, parietal lobe, sub
      lobar, cerebellum and midbrain regions were activated by acupuncture at the left
      LI11. On the other hand, only the right side of the inferior parietal lobule
      region was activated in the stroke patients. When the left ST36 was stimulated in
      the normal group, both sides of the frontal lobe, parietal lobe, temporal lobe,
      and sub-lobar, and the left side of occipital lobe, and the right side of
      cerebellum and midbrain regions were activated. For the same stimulation in the
      stroke group, only both sides of the inferior parietal lobule and cerebellum
      regions were activated (P<0.05, cluster level). Deactivation pattern was not
      noted during any acupuncture stimulation in both groups. CONCLUSION: Brain signal
      activations during the same acupuncture were different between the healthy and
      the stroke patients, and the effects showed a correlation of different
      acupuncture points.

PMID- 23546631
TI  - Electroacupuncture on PC6 prevents opioid-induced nausea and vomiting after
      laparoscopic surgery.
AB  - OBJECTIVE: To investigate the treatment time dependence of electroacupuncture
      (EA) on Neiguan (PC6) for preventing postoperative nausea and vomiting (PONV).
      METHODS: One hundred and seventy-eight patients, who had received intravenous
      patient-controlled analgesia (PCA) with Fentanyl, were assigned randomly to three
      groups using random numbers: a pre-operative EA group (PrEA), a post-operative EA
      group (PoEA), and a non-acupuncture control group (NC). An anesthetist evaluated
      the incidence and severity of nausea and vomiting for 48 h after surgery blindly.
      The main outcomes were severity and freguency of PONV, which were measured with a
      self-reported questionnaire and a confirmation from the anesthetist. The data
      were analyzed with ANOVA and Z-test. RESULTS: The incidence of nausea and
      vomiting was significantly lower in the PrEA group than the NC group during 48 h
      after surgery (P<0.01, P<0.05). The incidence of vomiting was also significantly
      lower in the PrEA group than the PoEA group (P<0.05). The PoEA subjects evidenced
      no significant differences compared with the NC subjects in terms of the
      incidence of nausea and vomiting (P<0.05). The severity of nausea was
      significantly lower in the PrEA group than in the NC and PoEA groups (P<0.05).
      CONCLUSIONS: EA on PC6 is effective in the prevention of PONV, and pre-operative
      acupuncture is more effective than post-operative acupuncture.

PMID- 23546632
TI  - Treatment of posthepatitic cirrhosis by Fuzheng Huayu Tablet for reinforcing qi
      and resolving stasis.
AB  - OBJECTIVE: To investigate the efficacy and safety of the Fuzheng Huayu Tablet
      FZHYT), which is used to reinforce qi and resolve stasis in patients with
      posthepatitic cirrhosis (PHC). METHODS: A multicenter, randomized, controlled
      clinical trial was conducted in 180 patients with PHC. The patients were randomly
      assigned using random numbers to a treatment group treated with FZHYT and a
      placebo group; the treatment course was 6 months for both groups. Overall
      response, adverse events (AEs), and the 2-year survival rate were assessed after
      treatment. Evaluations were made on changes in liver function, liver fibrosis,
      coagulation, hemodynamics, degrees of esophagogastric varices, ascites, quality
      of life (QOL), and scores of main symptoms. RESULTS: The overall response was
      significantly higher in the treatment group than the placebo group (86.7% vs.
      62.2%, P<0.01). Patients in both groups had significant improvements in liver
      function [total bilirubin (TBIL), albumin (ALB)], liver fibrosis [hyaluronic acid
      (HA), type IV collagen (CIV)], coagulation [prothrombin time (PT), activated
      partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)],
      hemodynamics portal venous flow (PVF), and splenic vein flow (SVF) after
      treatment. Between-group comparisons showed that compared with the placebo group
      patients in the treatment group achieved significantly greater improvements in
      TBIL, ALB, HA, C IV, PT, APTT, PVF, SVF, time to ascites resolution, 2-year
      survival, QOL, and symptom scores (P<0.05 or P<0.01). There were no significant
      AEs during the treatment. CONCLUSION: FZHYT is effective and safe for the
      treatment of hepatic cirrhosis as it is associated with improved liver function,
      liver fibrosis, coagulation, portal hypertension state, QOL, 2-year survival
      rate, and fewer AEs.

PMID- 23546633
TI  - Scalp acupuncture for Parkinson's disease: a systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: To evaluate the effectiveness of scalp acupuncture (SA), a modern
      acupuncture technique specialized to neurological disorders, in managing motor
      function and symptoms for Parkinson's disease (PD) patients. METHODS: Two
      independent reviewers extracted data from all of the randomized clinical trials
      (RCTs) that assessed the efficacy of SA for PD compared with conventional
      therapies (CTs). Sixteen electronic databases were searched. The risk of bias was
      appraised with the Cochrane Collaboration tool, and the reporting of the included
      studies was evaluated by the Consolidated Standards of Reporting Trials (CONSORT)
      2010 checklist and the revised Standards for Reporting Interventions in Clinical
      Trials of Acupuncture (STRICTA) guidelines. RESULTS: In total, 4 RCTs met the
      inclusion criteria. As assessed by the Unified PD Rating Scale (UPDRS), 2 RCTs
      showed that SA combined with CTs proved superior to CTs alone [60 cases; weighted
      mean difference, -3.94; 95% confidence interval (CI), -6.05 to -1.84, P=0.01;
      I(2) =0%]. Based on the Webster scale, however, 3 RCTs showed no superior effect
      of SA when combined with CTs with high heterogeneity (154 cases; risk ratio,
      1.29; 95% CI, 0.79 to 2.12, P=0.30; I(2) =84%). The Cochrane risk of bias,
      adherence to the CONSORT and the STRICTA checklist showed that the quality of all
      the included RCTs was generally low. CONCLUSIONS: The result of our systematic
      review and meta-analysis suggested that the effectiveness of SA for PD is
      promising, however, the evidence is not convincing. A sham-controlled RCT design
      that adheres to the CONSORT and STRICTA guidelines to overcome methodological
      weakness and that includes a large sample size is strongly recommended to confirm
      the precise effect of SA on PD.

PMID- 23546635
TI  - Recent advances in the molecular basis of anti-neoplastic mechanisms of oridonin.
AB  - Oridonin, a diterpenoid isolated from Rabdosia rubescens, has been proven to
      possess various pharmacological and physiological effects such as anti
      inflammation, anti-bacterial, and anti-neoplastic, although in recent years, more
      attention has been paid to its anti-neoplastic effects. For example, oridonin can
      trigger cell cycle arrest, apoptosis, and autophagy in different neoplastic cell
      lines. This review summarizes the considerable knowledge about the action
      mechanisms of oridonin that has been studied in recent years. The present
      observations reveal the novel anti-neoplastic effects of oridonin, suggesting
      that it may be effective as a potent alternative or adjunct drug to conventional
      chemotherapy.

PMID- 23546634
TI  - Pulse waveform analysis as a bridge between pulse examination in Chinese medicine
      and cardiology.
AB  - Pulse examination was probably the earliest attempt to distinguish between health
      and illnesses. Starting at the pre-Hippocratic era, Chinese medicine
      practitioners developed techniques for pulse examination and defined pulse images
      based on their perceptions of pulse waveforms at the radial artery. Pulse images
      were described using basic variables (frequency, rhythm, wideness, length,
      deepness, and qualities) developed under philosophical trends such as Taoism and
      Confucianism. Recent advances in biomedical instrumentation applied to cardiology
      opened possibilities to research on pulse examination based on ancient Chinese
      medical theories: the pulse wave analysis. Although strongly influenced by
      philosophy, some characteristics used to describe a pulse image are interpretable
      as parameters obtained by pulse waveform analysis such as pulse wave velocity and
      augmentation index. Those clinical parameters reflect concepts unique to Chinese
      medicine - such as yinyang - while are based on wave reflection and resonance
      theories of fluids mechanics. Major limitations for integration of Chinese and
      Western pulse examination are related to quantitative description of pulse images
      and pattern differentiation based on pulse examination. Recent evidence suggests
      that wave reflection and resonance phenomena may bridge Chinese medicine and
      cardiology to provide a more evidence-based medical practice.

PMID- 23546636
TI  - Multiscale analysis for a vector-borne epidemic model.
AB  - Traditional studies about disease dynamics have focused on global stability
      issues, due to their epidemiological importance. We study a classical SIR-SI
      model for arboviruses in two different directions: we begin by describing an
      alternative proof of previously known global stability results by using only a
      Lyapunov approach. In the sequel, we take a different view and we argue that
      vectors and hosts can have very distinctive intrinsic time-scales, and that such
      distinctiveness extends to the disease dynamics. Under these hypothesis, we show
      that two asymptotic regimes naturally appear: the fast host dynamics and the fast
      vector dynamics. The former regime yields, at leading order, a SIR model for the
      hosts, but with a rational incidence rate. In this case, the vector disappears
      from the model, and the dynamics is similar to a directly contagious disease. The
      latter yields a SI model for the vectors, with the hosts disappearing from the
      model. Numerical results show the performance of the approximation, and a
      rigorous proof validates the reduced models. 

PMID- 23546637
TI  - Travelling waves in a neural field model with refractoriness.
AB  - At one level of abstraction neural tissue can be regarded as a medium for turning
      local synaptic activity into output signals that propagate over large distances
      via axons to generate further synaptic activity that can cause reverberant
      activity in networks that possess a mixture of excitatory and inhibitory
      connections. This output is often taken to be a firing rate, and the mathematical
      form for the evolution equation of activity depends upon a spatial convolution of
      this rate with a fixed anatomical connectivity pattern. Such formulations often
      neglect the metabolic processes that would ultimately limit synaptic activity.
      Here we reinstate such a process, in the spirit of an original prescription by
      Wilson and Cowan (Biophys J 12:1-24, 1972), using a term that multiplies the
      usual spatial convolution with a moving time average of local activity over some
      refractory time-scale. This modulation can substantially affect network
      behaviour, and in particular give rise to periodic travelling waves in a purely
      excitatory network (with exponentially decaying anatomical connectivity), which
      in the absence of refractoriness would only support travelling fronts. We
      construct these solutions numerically as stationary periodic solutions in a co
      moving frame (of both an equivalent delay differential model as well as the
      original delay integro-differential model). Continuation methods are used to
      obtain the dispersion curve for periodic travelling waves (speed as a function of
      period), and found to be reminiscent of those for spatially extended models of
      excitable tissue. A kinematic analysis (based on the dispersion curve) predicts
      the onset of wave instabilities, which are confirmed numerically.

PMID- 23546638
TI  - Sleep and suicide: an analysis of a cohort of 394,000 Taiwanese adults.
AB  - BACKGROUND: Sleep problems may lead to, or be symptomatic of, depression and
      other mental illnesses yet few studies have investigated their association with
      suicide risk. DESIGN: Prospective cohort study. SETTING: Taiwan. PARTICIPANTS:
      393,983 men and women aged 20 or above participating in the MJ health check-up
      programme. RESULTS: There were 335 suicides over a mean of 7.4 years follow-up.
      There was a reverse J-shaped association between sleep duration and suicide risk.
      When compared with those sleeping 6-8 h per night the adjusted hazard ratios (95%
      confidence intervals) for suicide associated with 0-4, 4-6 and >8 h sleep were
      3.5 (2.0-6.1), 1.5 (1.1-1.9) and 1.5 (1.1-2.0), respectively. People requiring
      sleeping pills to get to sleep (1.2% participants) were at over 11-fold increased
      risk; difficulty falling asleep (11.5% participants), frequent dreaming (16.7%)
      and being easily awoken (30.6%) were associated with a 2.0-, 1.6- and 1.3-fold
      increased risk of suicide, respectively. CONCLUSIONS: Less than 6 h sleep
      duration, sleep disturbances and reported use of sleep medicines are markers of
      suicide risk. Sleep problems should be assessed when evaluating suicide risk.

PMID- 23546639
TI  - Ulinastatin suppresses lipopolysaccharide-induced prostaglandin E2 synthesis and
      nitric oxide production through the downregulation of nuclear factor-kappaB in
      BV2 mouse microglial cells.
AB  - Ulinastatin is an intrinsic serine-protease urinary trypsin inhibitor that can be
      extracted and purified from human urine. Urinary trypsin inhibitors are widely
      used to treat patients with acute inflammatory disorders, such as shock and
      pancreatitis. However, although the anti-inflammatory activities of urinary
      trypsin inhibitors have been investigated, the mechanisms underlying their
      actions are not yet fully understood. In the present study, we evaluated the
      effect of ulinastatin on lipopolysaccharide (LPS)-induced inflammation in
      relation with nuclear factor-kappaB (NF-kappaB) activation using BV2 mouse
      microglial cells. To accomplish this, we performed a 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase
      chain reaction (RT-PCR), western blot analysis, electrophoretic mobility gel
      shift assay (EMSA), prostaglandin E(2) (PGE(2)) immunoassay and nitric oxide (NO)
      detection. The results demonstrated that ulinastatin suppressed PGE2 synthesis
      and NO production by inhibiting the LPS-induced mRNA and protein expression of
      cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) in BV2 mouse microglial
      cells. Ulinastatin suppressed the activation of NF-kappaB in the nucleus. These
      findings demonstrate that ulinastatin exerts analgesic and anti-inflammatory
      effects that possibly occur via the suppression of COX-2 and iNOS expression
      through the downregulation of NF-kappaB activity.

PMID- 23546640
TI  - Ultrasound-assisted epidural anesthesia to amyotrophic woman.

PMID- 23546641
TI  - Hypoxia of PC-3 prostate cancer cells enhances migration and vasculogenesis in
      vitro of bone marrow-derived endothelial progenitor cells by secretion of
      cytokines.
AB  - Hypoxia is a key inducer of neovascularization which is essential for tumor
      growth, invasion and metastasis. It has been proposed that the recruitment of
      bone-marrow-derived endothelial progenitor cells (BM-EPCs) is pivotal and
      requires the participation of several tumor-derived cytokines. However, it is not
      known whether prostate cancer (PCa) cells contribute to the recruitment and
      vasculogenesis of EPCs in PCa progression. In the present study, we demonstrated
      that all conditioned medium (CM) of PC-3 PCa cells promoted proliferation and
      migration, and augmented the vasculogenesis capacity of BM-EPCs, and 24-h hypoxia
      (24H)-CM presented stronger ability compared to 24-h normoxia (24N)-CM and 48H
      CM. Human cytokine antibody array with 174 anti-cytokine antibodies revealed the
      changes of cytokine in CMs. Twenty-five types of cytokines significantly
      increased in 24H-CM compared with 24N-CM. Eleven types of cytokines (5 factors
      increased and 6 decreased) were significantly different between 48H-CM and 48N
      CM. Twelve types of cytokines (4 factors increased and 8 decreased) were
      significantly different between 48H-CM and 24H-CM. Furthermore, according to the
      gene ontology analysis, all altered cytokines were involved in proliferation,
      chemotaxis, cell motility, cell migration, vasculogenesis and angiogenesis. Of
      note, the changed regularity of cytokines in the 24H-CM and 48H-CM of PC-3 cells
      was in concert with the functional changes of BM-EPCs treated by different CM of
      PC-3 cells in enhancing the proliferation, migration and vasculogenesis potential
      of BM-EPCs. These findings suggest that PCa cells may have the potential to
      modulate their microenvironment and facilitate BM-EPC migration and
      vasculogenesis by secretion of cytokines in the early stage of hypoxia.

PMID- 23546642
TI  - Weighing benefits and risks: comment on "Use of glucocorticoids and risk of
      venous thromboembolism".

PMID- 23546643
TI  - NMDA receptor expression and C terminus structure in the rotifer Brachionus
      plicatilis and long-term potentiation across the Metazoa.
AB  - The C termini of N-methyl-D-aspartate (NMDA) receptor NR2 subunits are thought to
      play a major role in the molecular establishment of memory across the Bilateria,
      via the phenomenon known as long-term potentiation (LTP). Despite their long
      history of use as models in the study of memory, the expression and structure of
      the NR2 subunit in the Lophotrochozoa has remained uncategorized. Here, we report
      the phylogenic relationships of NR subunits across the Bilateria, and the cloning
      and in situ analysis of expression of NMDA NR1 and NR2 subunits in the monogont
      rotifer Brachionus plicatilis. RNA in situ hybridization suggests expression of
      NMDA receptor subunits in B. plicatilis is neural, consistent with expression
      observed in other species, and ours is the first report confirming NR2 expression
      in the lophotrochozoan clade. However, the single NR2 subunit identified in B.
      plicatilis was found to lack the long C terminal domain found in vertebrates,
      which is believed to modulate LTP. Further investigation revealed that mollusc
      and annelid NR2 subunits possess long intracellular C terminal domains. As data
      from molluscs (and particularly Aplysia californica) are the basis for much of
      our understanding of LTP, understanding how these diverse lophotrochozoan C
      termini function in vivo will have many implications for how we consider the
      evolution of the molecular control of learning and memory across the Metazoa as a
      whole and interpret the results of experiments into this vital component of
      cognition. 

PMID- 23546644
TI  - Analysis of the molecular pathophysiology of sleep disorders relevant to a
      disturbed biological clock.
AB  - Genetic studies have revealed several clock gene variations/mutations involved in
      the manifestation of sleep disorders or interindividual differences in sleep-wake
      patterns, but only part of the genetic risk can be explained by the gene
      variations/mutations identified to date. Recent progress in research into
      circadian rhythm generation has provided efficient tools for eliciting the
      molecular basis of clock-relevant sleep disorders, complementing traditional
      genetic analysis. While the human master clock resides in the suprachiasmatic
      nucleus of the hypothalamus (central clock), peripheral tissue cells also
      generate self-sustained circadian oscillations of clock gene expression
      (peripheral clock), enabling estimation of individual human clock properties
      through a single collection of skin fibroblasts or venous blood cells. Some of
      the established cell lines exhibit autonomous circadian oscillations of clock
      gene expression, and introduction of clock gene variations into these cell lines
      by gene targeting makes it possible to investigate changes in the circadian
      phenotype induced by these variations/mutations without the need for generating
      transgenic animals. Estimation of human clock properties using peripheral tissue
      cells, in addition to genetic analysis, will facilitate comprehensive explication
      of the genetic risk of a variety of disorders relevant to biological clock
      disturbances, including sleep disorders, mood disorders, and metabolic diseases.

PMID- 23546645
TI  - Validation of the Chinese version of the Boston Carpal Tunnel Questionnaire.
AB  - PURPOSE: Carpal tunnel syndrome (CTS) is a common diagnosis occurring in the
      workplace when people experience hand or wrist symptoms and difficulty performing
      activities. This study aimed to investigate the psychometric properties of the
      Chinese version of the Boston Carpal Tunnel Questionnaire (BCTQ) used to evaluate
      patients with CTS. METHODS: A convenience sample of patients with CTS was
      recruited from two hospitals. The Symptom Severity Scale (SSS) and Functional
      Status Scale (FSS) of the BCTQ were used to assess symptoms and functional
      status. Test-retest reliability within 1 week was evaluated (n = 51). Construct
      validity was assessed by examining the relationship between the BCTQ and other
      well known measures (n = 99). Responsiveness of the scale was examined pre- and
      post-operatively for patients undergoing carpal tunnel surgery (n = 23). RESULTS:
      High reliability was demonstrated through intraclass correlation coefficients of
      0.81 and 0.83 for SSS and FSS, respectively. The minimal detectable change was
      0.86 and 0.75 for SSS and FSS, respectively. Convergent validity was supported by
      high correlation of both scales with Disability of the Arm, Shoulder and Hand
      (|rho| = 0.63, 0.75 for SSS and FSS), and moderate to high correlation with the
      subscales of the Short-Form 36 for SSS(|rho| = 0.72 for Body Pain) and FSS (|rho|
      = 0.48 for Physical Function). Responsiveness was confirmed by moderate to high
      standardized response means for SSS (1.03) and FSS (0.62). CONCLUSION: The
      Chinese BCTQ is a reliable, valid and responsive disease-specific measure for
      assessment of symptoms and functional status in patients with CTS.

PMID- 23546646
TI  - The growth trends of Korean adolescents with bialveolar protrusion: a nine year
      longitudinal cephalometric study.
AB  - Bialveolar protrusion and dental crowding seems to have common features in terms
      of aetiology and treatment method, although they result in different facial
      profiles and tooth alignment. The aim of this longitudinal study is to determine
      when children begin to show bialveolar protrusive traits in order to get more
      clue about the aetiology of bialveolar protrusion. Longitudinal lateral
      cephalometric data of children followed from 6 to 14 years of age were used. A
      total of 155 children (81 girls and 74 boys) with showing Class molar
      relationships at the age of 14 were assigned to either the protrusive group (PG)
      or the non-protrusive group (NPG), based on 5 cephalometric measurements. The
      cephalometric measurements of these 2 groups were compared at each age separately
      in both sexes by independent t-tests. Throughout the entire observation period,
      there were differences between PG and NPG in both sexes in measurements which
      were used for classification at 14 years of age. There were differences between
      sexes in both PG and NPG in several measurements of at several different ages.
      Individuals with bialveolar protrusive traits at the age of 14 exhibited the
      signs early in life, at least from the early mixed dentition.

PMID- 23546647
TI  - Axotomy-induced changes in the chemical coding pattern of colon projecting
      calbindin-positive neurons in the inferior mesenteric ganglia of the pig.
AB  - The present study examines the response of colon-projecting neurons localized in
      the inferior mesenteric ganglia (IMG) to axotomy in the pig animal model. In all
      animals (n = 8), a median laparotomy was performed under anesthesia and the
      retrograde tracer Fast Blue was injected into the descending colon wall. In
      experimental animals (n = 4), the descending colon was exposed and the bilateral
      caudal colonic nerves were identified and severed. All animals were euthanized
      and the inferior mesenteric ganglia were harvested and processed for double
      labeling immunofluorescence for calbindin-D28k (CB) in combination with either
      tyrosine hydroxylase (TH), neuropeptide Y (NPY), somatostatin (SOM), vasoactive
      intestinal polypeptide (VIP), nitric oxide synthase (NOS), Leu-enkephalin (LENK),
      substance P, vesicular acetylcholine transporter, or galanin.
      Immunohistochemistry revealed significant changes in the chemical coding pattern
      of injured inferior mesenteric ganglion neurons. In control animals, Fast Blue
      positive neurons were immunoreactive to TH, NPY, SOM, VIP, NOS, LENK, and CB. In
      the experimental group, the numbers of TH-, NPY-, and SOM-expressing neurons were
      reduced, whereas the number of neurons immunoreactive to LENK was increased. Our
      data indicate that the colon-projecting neurons of the porcine IMG react to the
      axotomy in a similar, but not an identical manner in a comparison to other
      species, especially rodents. Further studies are needed to elucidate the detailed
      factors/mechanisms involved in the response to nerve injury. 

PMID- 23546648
TI  - Association of serum total bilirubin levels with the severity, extent and
      subtypes of coronary atherosclerotic plaques detected by coronary CT angiography.
AB  - In this study, we aimed to evaluate whether serum total bilirubin was associated
      with the severity and morphology of coronary atherosclerotic plaques detected by
      computed tomography angiography (CTA). The study population consisted of 1,115
      patients (55.2 % men) who underwent dual-source 64-slice CTA for the assessment
      of coronary artery disease (CAD). Coronary arteries were evaluated on 16 segment
      basis and critical coronary plaque was described as luminal narrowing >50 %,
      whereas plaque morphology was assessed on per segment basis. Serum bilirubin
      levels were determined using commercially available assay kits. The critical
      atherosclerotic lesions were detected in 431/1,115 (38.6 %) subjects by CTA.
      Serum total bilirubin levels were found to be lower in patients with any coronary
      plaque (0.62 +/- 0.21 vs. 0.70 +/- 0.25 mg/dL, p = 0.002). Also bilirubin level
      was lower in patients with critical stenosis compared to non-critical stenosis
      (0.57 +/- 0.18 vs. 0.70 +/- 0.24 mg/dL, p < 0.001). Subjects having primarily
      noncalcified plaque (NCP) and mixed plaque (MP) have lower bilirubin levels
      compared to calcified plaque (CP) and normal subjects (0.62 +/- 0.20 for NCP and
      0.60 +/- 0.19 for MP, 0.65 +/- 0.26 for CP and 0.71 +/- 0.25 for normal subjects,
      p < 0.001). This independent association was remained for NCP after multinominal
      regression analysis (OR: 0.76; 95 % CI 0.58-0.88; p < 0.001). Our study
      demonstrated that serum bilirubin level was significantly associated with the
      presence, severity and the noncalcified morphology of atherosclerotic plaques
      detected by CTA. Further prospective clinical studies are needed to clarify the
      exact physiopathologic and prognostic role of bilirubin in CAD.

PMID- 23546649
TI  - Angiographic validation of magnetic resonance assessment of myocardium at risk in
      non-ST-elevation myocardial infarction.
AB  - In the setting of acute myocardial ischemia, the hypoperfused portion of the
      myocardium is in danger of becoming irreversibly injured. This portion is called
      the area at risk (AAR). It is of clinical interest to be able to estimate the AAR
      for further evaluation and improvement of different revascularization strategies.
      The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease
      Score (APPROACH-score) has been shown to be a jeopardy score with a good
      performance for angiographic assessment of the myocardium supplied by a coronary
      vessel, representing the AAR. Recently, cardiac magnetic resonance imaging (CMR)
      has been demonstrated to also provide good results in determining the AAR,
      especially in the setting of acute ST-elevation infarction patients. Therefore,
      the aim of our trial was to compare T2-weighted CMR imaging for assessment of AAR
      in patients with non-ST-elevation myocardial infarction (NSTEMI) and to validate
      this approach against the angiographic APPROACH-score. We enrolled sixty-four
      patients presenting with acute NSTEMI that underwent coronary X-ray angiography
      within 72 h of symptom onset. Two blinded readers performed offline angiographic
      AAR assessment using the modified APPROACH-score, as being described elsewhere.
      Furthermore, with the use of a semi-automatic T2w-CMR approach, the AAR was
      quantified by two fully blinded readers. The resulting mean AAR determined by the
      modified APPROACH-score was 28.6 +/- 10.0 %. The mean CMR derived AAR was 27.6 +/
      12.7 %. CMR assessment tended to slightly underestimate the AAR in comparison to
      angiographic scoring (difference -0.09 +/- 7.6 %). There is a good correlation
      between the AAR assessed by CMR and by angiography (r = 0.65, p < 0.001). T2
      weigthed CMR is able to quantify the AAR with very good correlation to the
      angiographic APPROACH-score in NSTEMI patients.

PMID- 23546650
TI  - Endoscopic findings of asymptomatic patients one year after Roux-en-Y gastric
      bypass for treatment of obesity.
AB  - BACKGROUND: In the late post-operative period, the necessity of performing an
      upper gastrointestinal endoscopy (GIE) to check for complications is
      controversial. Some authors suggest it should be routine for all patients, others
      selectively, but not all patients with endoscopic abnormalities are symptomatic
      and some abnormalities are potentially severe. The study was conducted to
      evaluate the endoscopic findings from asymptomatic obese patients after Roux-en-Y
      gastric bypass (RYGB) and correlate them with the demographic data and the
      presence of Helicobacter pylori (Hp). METHODS: A total of 715 asymptomatic
      patients were prospectively submitted to an upper GIE at the end of their first
      post-operative year. These examinations were evaluated for the presence of
      abnormalities, their prevalence and their potential severity. RESULTS:
      Abnormalities were found in 189 patients (26.5 %). Eighty-four (11.7 %) presented
      esophageal abnormalities, with 72 (10.1 %) characterized as esophagitis and 12
      (1.7 %) as hiatal hernia. Forty-five patients (6.3 %) presented abnormalities of
      the stomach and the anastomosis, with 26 (3.6 %) characterized as anastomotic
      ulcers, nine (1.3 %) as stenosis of the gastrojejunal anastomosis, ten (1.4 %) as
      band erosion and 72 (10.1 %) as jejunitis. There was a statistically significant
      correlation between super obesity and band erosion. CONCLUSIONS: An upper GIE at
      the end of the first year of RYGB plays an important role, even for asymptomatic
      patients. One fourth of these asymptomatic patients had their treatment modified
      after the upper GIE was performed.

PMID- 23546651
TI  - Do preoperative eating behaviors influence weight loss after biliopancreatic
      diversion?
AB  - BACKGROUND: The presence of disturbed eating patterns can affect the short- and
      long-term outcomes after bariatric surgery. Data about the influence of
      preoperative eating patterns on outcomes after biliopancreatic diversion (BPD)
      are lacking. The aim of the present study was to assess the role of preoperative
      eating behavior in patients' selection for biliopancreatic diversion. METHODS:
      Sixty-one consecutive patients who underwent BPD were evaluated for the present
      study. For each patient, the following preoperative eating patterns were
      evaluated: sweet eating, snacking, hyperphagia, and gorging. The primary outcome
      measure was the percentage of excess weight loss (%EWL) at 3, 6, and 12 months in
      the groups of patients with different eating patterns at the preoperative
      evaluation. RESULTS: At the preoperative evaluation, snacking was found in 31
      patients (50.8 %), sweet eating in 15 patients (24.6 %), hyperphagia in 48
      patients (78.7 %), and gorging in 45 patients (73.8 %). For each eating behavior,
      there was no significant difference in mean preoperative BMI and weight loss at
      3, 6, and 12 months between the group of patients with and the group of patients
      without the eating pattern considered. At the analysis of variance in the four
      groups of patients presenting the eating patterns considered, there was no
      difference in mean preoperative BMI (P = 0.66), %EWL at 3 months (P = 0.62), %EWL
      at 6 months (P = 0.94), and %EWL at 12 months (P = 0.95). CONCLUSIONS:
      Preoperative eating behaviors do not represent reliable outcome predictors for
      BPD, and they should not be used as a selection criterion for patients who are
      candidates to this operation.

PMID- 23546652
TI  - Self-locking first stitch in suture reinforcement of the laparoscopic gastric
      sleeve.

PMID- 23546653
TI  - Nanoparticle-GFP "chemical nose" sensor for cancer cell identification.
AB  - Nanoparticle-based sensor arrays have been used to distinguish a wide range of
      bio-related molecules through pattern recognition. This "chemical nose" approach
      uses nanoparticles as receptors to selectively identify the analytes, while a
      transducer reports the binding through a readable signal (fluorescence). Here we
      describe a procedure that uses functionalized gold nanoparticles as receptors and
      green fluorescent protein (GFP) as the transducer to identify and differentiate
      cell state (normal, cancerous, and metastatic), an important tool in early
      diagnosis and treatment of tumors.

PMID- 23546654
TI  - A method to map spatiotemporal pH changes in a multicellular living organism
      using a DNA nanosensor.
AB  - Environmental pH has a determining role in the structure of biomolecules, thus
      playing an important role in regulating cellular activities. Eukaryotic cells
      must, therefore, strive to stringently regulate pH in various intracellular
      organelles so as to confer normal functioning at the level of whole organism.
      Several pH-sensitive probes have been reported, each of which can be used to map
      the pH dependence of an in vivo process. However, these probes suffer from some
      inherent drawbacks. Here we demonstrate the utility of an externally introduced,
      pH-triggered DNA nanomachine inside the multicellular eukaryote Caenorhabditis
      elegans. The nanomachine uses FRET to effectively map spatiotemporal pH changes
      associated with endocytosis in coelomocytes of wild type as well as mutant worms,
      in a variety of genetic backgrounds. It shows highest dynamic range in the pH
      regime 5.3-6.6 and has a half-life of ~8 h, thus positioning it well to
      interrogate a variety of pH-correlated biological phenomena in vivo.

PMID- 23546655
TI  - A simple method to visualize and assess the integrity of lysosomal membrane in
      mammalian cells using a fluorescent dye.
AB  - Fluorescent dyes have been used as "nanosensors" for visualization and
      determination of various processes occurring inside a cell, or intracellular
      events, such as cell cycle progression and intracellular trafficking. Here, we
      describe a novel use of acridine orange to visualize lysosomes and discriminate
      cells with healthy lysosomes from cells with damaged lysosomes in two different
      types of mammalian cells: fibroblasts and macrophages. This method allows
      assessment of lysosomal membrane integrity upon exposure to various foreign
      particles, i.e., engineered nanoparticles. The uniqueness of this method enables
      investigators to acquire fluorescent images with a dye that is susceptible to
      photo-bleaching under UV light. These acquired images bolster the quantitative
      data, providing a visual representation of the cell morphology as well as assess
      its nucleus and lysosomes.

PMID- 23546656
TI  - Gold nanoparticle as a marker for precise localization of nano-objects within
      intracellular sub-domains.
AB  - Delivery of nano-objects to certain intracellular sub-domains is crucial for
      nanomedicine. Therefore delivery of nano-object to desirable cellular compartment
      has to be confirmed. The most valuable confirmation of the delivery comes from
      direct visualization of the nano-object. This visualization usually requires use
      of microscope and corresponding probe which has to be conjugated with the nano
      object. There are two most popular methods of the visualization: confocal and
      electron microscopy. The former has significant limitations due to diffraction
      limited resolution of confocal systems and three-dimensional convolution of
      fluorescence. The latter should be significantly modified for needs of the
      visualization. Here we describe the method for precise localization of nano
      object within the cell using electron microscopy and 1-2 nm gold particles as a
      nanomarker.

PMID- 23546657
TI  - Immunoisolation of nanoparticles containing endocytic vesicles for drug
      quantitation.
AB  - Cell-mediated nanoparticle delivery has recently emerged as an efficacious method
      of delivering therapeutic agents across physiological barriers. Use of cells as
      nanodelivery vehicles requires accurate assessment of their loading capacity and
      identification of intracellular compartments where nanoparticles are sequestered.
      This is of great interest since specific endocytic trafficking routes can
      ultimately influence the mode of nanoparticle release and their efficacy and
      function. Here, we describe a technique that allows for the isolation of
      individual populations of nanoparticle-containing endosomes for subsequent
      quantitative analysis and more accurate description of where nanoparticles are
      stored on a subcellular level.

PMID- 23546658
TI  - Methods for isolation and identification of nanoparticle-containing subcellular
      compartments.
AB  - Nanoparticle-based drug delivery systems have considerable potential for
      improvement of drug stability, bioavailability, and reduced dosing frequency.
      Important technological advantages of nanoparticles include high carrier capacity
      across biological membranes and controlled drug release. Ultimately, success of
      nanodelivery systems depends on toxicologic issues associated with the
      understanding of the fate of nanocarriers and their polymeric constituents within
      the targeted cells. Here we describe a method for determining subcellular
      distribution of nanoparticles by isolation and identification of organelles that
      come in direct contact with these structures.

PMID- 23546659
TI  - Permeabilization of cell membrane for delivery of nano-objects to cellular sub
      domains.
AB  - Delivery of nano-objects to specific cellular sub-domains is a challenging but
      intriguing task. There are two major barriers on the way of a nano-object to its
      intracellular target: (1) the cell membrane and (2) the intracellular barriers.
      The former is a common issue for all nanomedicine and a matter of very intense
      research. The latter is the primary problem for targeted delivery of nano-objects
      to specific cellular sub-domains and can be studied more easily using
      permeabilized cells. Membrane permeabilization for nanomedical research requires
      (1) perforation of the outer membrane, (2) development of a solution that will
      keep cellular sub-domains in the functional state, and (3) modification of the
      perimembrane cytoskeleton. We developed a very successful model of saponin
      membrane permeabilization of cardiomyocytes. This allowed us to deliver particles
      up to 20 nm in size to perinuclear and perimitochondrial space. Here we describe
      the method.

PMID- 23546660
TI  - A method to encapsulate molecular cargo within DNA icosahedra.
AB  - DNA self-assembly has yielded various polyhedra based on platonic solids. DNA
      polyhedra can act as nanocapsules by entrapping various molecular entities from
      solution and could possibly find use in targeted delivery within living systems.
      A key requirement for encapsulation is that the polyhedron should have maximal
      encapsulation volume while maintaining minimum pore size. It is well known that
      platonic solids possess maximal encapsulation volumes. We therefore constructed
      an icosahedron from DNA using a modular self-assembly strategy. We describe a
      method to determine the functionality of DNA polyhedra as nanocapsules by
      encapsulating different cargo such as gold nanoparticles and functional
      biomolecules like FITC dextran from solution within DNA icosahedra.

PMID- 23546661
TI  - Delivery of plasmid DNA to mammalian cells using polymer-gold nanorod assemblies.
AB  - Functionalized and surface-modified gold nanorods (GNRs) have emerged as
      promising vehicles for the delivery of several therapeutic agents. Ease of
      functionalization, increased stability, biocompatibility, and size-dependent
      plasmonic properties make gold nanorods attractive in sensing, imaging, and
      delivery to different cellular types. Here, we demonstrate the use of
      polyelectrolyte-coated GNRs (PE-GNRs) for delivering plasmid DNA to mammalian
      cells for transgene expression.

PMID- 23546662
TI  - Lipophilic-formulated gold porphyrin nanoparticles for chemotherapy.
AB  - Lipophilic formulation is an invaluable technique for the delivery of cancer
      drugs. Incorporation of poorly soluble and toxic compounds into a lipophilic
      carrier vehicle improves both the stability and compatibility in blood and body
      fluids. Currently, although a large proportion of novel cancer drugs are poorly
      water soluble, most existing drug carriers are only able to encapsulate
      hydrophilic drugs. As the ultimate goal of drug delivery (in particular cancer
      drug delivery) is to achieve high therapeutic effect with minimal toxicity, it
      would thus be beneficial to invest substantial efforts in the development of
      lipophilic carrier systems. Here we describe our technique to synthesize a
      lipophilic carrier for hydrophobic and toxic potent cancer drugs, such as
      gold(III) porphyrin.

PMID- 23546663
TI  - Mitochondria-specific nano-emulsified therapy for myocardial protection against
      doxorubicin-induced cardiotoxicity.
AB  - The quinonoid anthracycline, doxorubicin (Adriamycin), is a widely used potent
      antineoplastic agent, showing the broadest spectrum of antineoplastic activity
      against various types of solid carcinomas, hematological malignancies, and soft
      tissue sarcomas. Unfortunately, the clinical use of doxorubicin is associated
      with cumulative dose-limiting cardiac toxicity, manifested as cardiomyopathy and
      congestive heart failure, in which mitochondrial damage is primarily implicated.
      Free radical formation at and inside mitochondria, in particular the rise of
      reactive oxygen species (ROS), has long been hypothesized as the common mechanism
      by which doxorubicin causes this severe cardiotoxicity. Concomitant with newly
      gained insights into the central role of mitochondria in programmed cell death
      (apoptosis), irreversible destabilization of mitochondrial membrane permeability
      transition (mMPT), and disruption of mitochondrial Ca(2+) homeostasis have been
      strongly implicated in triggering myocardial apoptosis, due to accumulated
      doxorubicin dosing. Hence, our current protocols show the development of
      mitochondria-targeted nanoemulsions (NEs), based on previous work using nano
      vesicle surface modification with mitochondriotropic triphenylphosphonium (TPP)
      ligands, which have successfully been demonstrated to target drug and DNA-loaded
      liposomes to mitochondria in living mammalian cells. Our mitochondria-specific
      TPP-coated therapeutic NEs are prepared using tocopherol oxygen scavengers and
      are highly loaded with mitochondria-stabilizing therapeutics, namely,
      cyclosporine A (CsA). Our targeted nano-formulation, proposed as injectable
      adjuvant therapy, is capable of reaching target affected mitochondria in
      sufficient therapeutic concentration, in order to revert or at least limit
      oxidative and non-oxidative doxorubicin-induced mitochondrial damage, manifested
      in affected cardiac muscle tissues, Based on several encouraging studies using in
      vitro model rat cardiac muscle, H9C2 cardiomyocytes, and vascular media tunica
      media, A10, cell cultures, our proof-of principal mitochondriotropic nano-therapy
      demonstrates strong potential to improve not only the cardiac safety profile,
      through concurrent rescue administration of targeted nano-encapsulated FDA
      approved cyclosporine A (CSA), but also dosing range of the currently available
      potent adriamycin/doxorubicin-based chemotherapy regimens.

PMID- 23546664
TI  - Formation of pit-spanning phospholipid bilayers on nanostructured silicon dioxide
      surfaces for studying biological membrane events.
AB  - Zwitterionic phospholipid vesicles are known to adsorb and ultimately rupture on
      flat silicon dioxide (SiO2) surfaces to form supported lipid bilayers. Surface
      topography, however, alters the kinetics and mechanistic details of vesicles
      adsorption, which under certain conditions may be exploited to form a suspended
      bilayer. Here we describe the use of nanostructured SiO2 surfaces prepared by the
      colloidal lithography technique to scrutinize the formation of suspended 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers from a
      solution of small unilamellar lipid vesicles (SUVs). Atomic force microscopy
      (AFM) and quartz crystal microbalance with dissipation monitoring (QCM-D) were
      employed to characterize nanostructure fabrication and lipid bilayer assembly on
      the surface.

PMID- 23546665
TI  - Characterization of nanoparticle-lipid membrane interactions using QCM-D.
AB  - In vitro characterization of nanoparticles is becoming increasingly important due
      to the rapid development of novel nanoparticle formulations for applications in
      the field of nanomedicine and related areas. Commonly, nanoparticles are simply
      characterized with respect to their size and zeta potential, and additional in
      vitro characterization of nanoparticles is needed to develop useful nanoparticle
      structure-activity relationships. In this context it is highly interesting to
      characterize the interactions between nanoparticles and model interfaces, such as
      lipid membranes. Here, we describe a methodology to study such interactions using
      the quartz crystal microbalance with dissipation monitoring technique (QCM-D). In
      order to mimic some aspects of the native cell membrane, a supported lipid
      membrane is formed on the QCM-D sensor surface. Subsequently the membrane is
      exposed to nanoparticles, and the nanoparticle-lipid membrane interactions are
      monitored in real time. The outcome of such analysis provides information on the
      adsorption process (importantly kinetics and adsorbed amounts) as well as on the
      integrity of both the nanoparticles and the lipid membrane upon interaction. QCM
      D analyses are suitable for screening of nanoparticle-lipid membrane interactions
      due to the fair throughput of the technique, which can be complemented, when
      needed, by additional analyses by other surface-sensitive analytical techniques.

PMID- 23546666
TI  - Single-cell nanosurgery.
AB  - This chapter explains the steps necessary to perform laser surgery upon single
      adherent mammalian cells, where individual organelles are extracted from the
      cells by optical tweezers and the cells are monitored post-surgery to check their
      viability. Single-cell laser nanosurgery is used in an increasing range of
      methodologies because it offers great flexibility. Its main advantages are (a)
      there is not any physical contact with the cells so they remain in a sterile
      environment, (b) high spatial selectivity so that single organelles can be
      extracted from specific areas of individual cells, (c) the method can be
      conducted in the cell's native media, and (d) in comparison to other techniques
      that target single cells, such as micromanipulators, laser nanosurgery has a
      comparatively high throughput.

PMID- 23546667
TI  - Single quantum dot imaging in living cells.
AB  - Direct visualization of biological processes at single-molecule level provides a
      detailed perspective which conventional bulk measurements are hard to achieve.
      Among various classes of fluorescent tags used in single-molecule tracking,
      quantum dots are particularly useful due to their unique photophysical
      properties. In this chapter, we describe the principles, methodologies, and
      experimental protocols for qdot-based single-molecule imaging. The first half
      provides an overview of fluorescent microscopy and advances in single-molecule
      tracking using quantum dots. The remainder of this chapter describes methods to
      carry out qdot-based single-molecule experiments. Detailed protocols including
      qdot labeling, microscopy setup, and single-molecule analysis using appropriate
      computational programs are given.

PMID- 23546668
TI  - Fabrication of fluorescent silica nanoparticles with aggregation-induced emission
      luminogens for cell imaging.
AB  - Fluorescence-based techniques have found wide applications in life science. Among
      various luminogenic materials, fluorescent nanoparticles have attracted much
      attention due to their fabulous emission properties and potential applications as
      sensors. Here, we describe the fabrication of fluorescent silica nanoparticles
      (FSNPs) containing aggregation-induced emission (AIE) luminogens. By employing
      surfactant-free sol-gel reaction, FSNPs with uniform size and high surface charge
      and colloidal stability are generated. The FSNPs emit strong light upon
      photoexcitation, due to the AIE characteristic of the silole -aggregates in the
      hybrid nanoparticles. The FSNPs are cytocompatible and can be utilized as
      fluorescent visualizer for intracellular imaging for HeLa cells.

PMID- 23546669
TI  - Monitoring the degradation of reduction-sensitive gene carriers with fluorescence
      spectroscopy and flow cytometry.
AB  - Polycations like poly(ethylene imine) (PEI) or poly(L-lysine) (pLL) form
      nanometer-sized complexes with nucleic acids (polyplexes) which can be used for
      gene delivery. It is known that the properties of these -carriers can be greatly
      improved by introducing disulfide bridges on the polymers, thus making them
      reduction sensitive. However, little is known about how such modified carriers
      behave intracellularly. Here, we describe a method that uses the reduction
      sensitive fluorescent dye BODIPY FL L-cystine to label PEI and pLL. Our probe is
      activated under reductive conditions leading to strongly increased fluorescence
      intensity. Subsequently, we show how the intracellular route of polyplexes made
      from these labeled polymers can be monitored by flow cytometry.

PMID- 23546670
TI  - Quantification of intracellular mitochondrial displacements in response to
      nanomechanical forces.
AB  - Mechanical stress affects various aspects of cell behavior, including cell
      growth, morphology, differentiation, and genetic expression. Here, we describe a
      method to quantify the intracellular mechanical response to an extracellular
      mechanical perturbation, specifically the displacement of mitochondria. A
      combined fluorescent-atomic force microscope (AFM) was used to simultaneously
      produce well-defined nanomechanical stimulation to a living cell while optically
      recording the real-time displacement of fluorescently labeled mitochondria. A
      single-particle tracking (SPT) approach was then applied in order to quantify the
      two-dimensional displacement of mitochondria in response to local forces.

PMID- 23546671
TI  - Imaging select mammalian organelles using fluorescent microscopy: application to
      drug delivery.
AB  - The microscopic imaging of specific organelles has become a staple of the single
      cell assay and has helped define the molecular regulation of many physiological
      processes. This definition has been made possible by utilizing different criteria
      to identify specific subpopulations of organelles. These criteria can be
      biochemical, immunological, or physiological, and in many cases, markers regulate
      fusion to the organelle they define (e.g., Rab-GTPase proteins). Single-cell
      imaging technology allows, within the context of drug delivery, an evaluation of
      the intracellular trafficking of both biological and synthetic macromolecules.
      However, it should be remembered that there are many limitations associated with
      this type of study and quantitation is not easy. The temporal dissection of novel
      and default trafficking of both macromolecular "drugs" and macromolecular drug
      delivery systems is possible. These methodologies are detailed herein.

PMID- 23546672
TI  - Real-time particle tracking for studying intracellular trafficking of
      pharmaceutical nanocarriers.
AB  - Real-time particle tracking is a technique that combines fluorescence microscopy
      with object tracking and computing and can be used to extract quantitative
      transport parameters for small particles inside cells. Since the success of a
      nanocarrier can often be determined by how effectively it delivers cargo to the
      target organelle, understanding the complex intracellular transport of
      pharmaceutical nanocarriers is critical. Real-time particle tracking provides
      insight into the dynamics of the intracellular behavior of nanoparticles, which
      may lead to significant improvements in the design and development of novel
      delivery systems. Unfortunately, this technique is not often fully understood,
      limiting its implementation by researchers in the field of nanomedicine. In this
      chapter, one of the most complicated aspects of particle tracking, the mean
      square displacement (MSD) calculation, is explained in a simple manner designed
      for the novice particle tracker. Pseudo code for performing the MSD calculation
      in MATLAB is also provided. This chapter contains clear and comprehensive
      instructions for a series of basic procedures in the technique of particle
      tracking. Instructions for performing confocal microscopy of nanoparticle samples
      are provided, and two methods of determining particle trajectories that do not
      require commercial particle-tracking software are provided. Trajectory analysis
      and determination of the tracking resolution are also explained. By providing
      comprehensive instructions needed to perform particle-tracking experiments, this
      chapter will enable researchers to gain new insight into the intracellular
      dynamics of nanocarriers, potentially leading to the development of more
      effective and intelligent therapeutic delivery vectors.

PMID- 23546673
TI  - Interactions of nanoparticles with proteins: determination of equilibrium
      constants.
AB  - The behavior of nanoparticles towards proteins is an important aspect across wide
      areas of nanotoxicology and nanomedicine. In this chapter, we describe a
      procedure to study the adsorption of proteins onto nanoparticle surfaces.
      Circular dichroism (CD) spectroscopy is utilized to quantify the amount of free
      protein in a solution, and the experimental information is evaluated to derive
      equilibrium constants for the protein adsorption/desorption equilibrium. These
      equilibrium constants are comparable parameters in describing the interactions
      between proteins and nanoparticles.

PMID- 23546674
TI  - Tracing the endocytic pathways and trafficking kinetics of cell signaling
      receptors using single QD nanoparticles.
AB  - Cellular signaling is the fundamental process through which cells communicate
      with each other and respond to their environment. Regulation of this cellular
      signaling is crucial for healthy cellular function. Malfunctions in signaling are
      the cause for many diseases and disorders and therefore are under heavy
      investigation. The molecular mechanisms that underlie cellular signaling rely
      upon complex and dynamic processes of receptor intracellular trafficking. The
      specific endosomal pathways and kinetics through which receptors are
      intracellularly transported regulate the strength and duration of cellular
      signaling. In even more subtle and complex aspects, the cell orchestrates the
      individual motions of many receptors, through multiple different pathways,
      simultaneously. Despite the fundamental role of endosomal trafficking in signal
      regulation, it has been technically challenging to study since intracellular
      trafficking is complex and dynamic, with millions of individual receptors
      simultaneously undergoing trafficking in different endocytic stages. Here, we
      describe the use of single nanoparticle quantum dot (QD) probes to quantitatively
      investigate the endocytic trafficking pathways that receptors undergo following
      ligand activation. This new capability to directly visualize and quantitate
      cellular signaling at the level of individual receptors inside the cell has broad
      and important value for understanding fundamental cell signaling processes and
      the action and effect of therapeutics upon signaling.

PMID- 23546675
TI  - Cellular internalization of quantum dots.
AB  - Cell-penetrating peptides (CPPs) can facilitate uptake of quantum dots (QDs) for
      a variety of basic and applied sciences. Here we describe a method that utilizes
      simple noncovalent interactions to complex QDs and CPPs. We further describe
      methods to study uptake mechanisms of the QD/CPP complex. The inhibitor study
      coupled with the RNA interference (RNAi) technique provides a comprehensive
      approach to elucidate cellular entry of the QD/CPP complex.

PMID- 23546676
TI  - Electrochemical scanning tunneling microscopy and spectroscopy for single
      molecule investigation.
AB  - The technique of electrochemical scanning tunneling microscopy (ECSTM) and
      spectroscopy (ECSTS) for studying electron transport through single redox
      molecules is here described. Redox molecules of both biological and organic
      nature have been studied by this technique with the aim of understanding the
      transport mechanisms ruling the flow of electrons via a single molecule placed in
      a nanometer-sized gap between two electrodes while elucidating the role of the
      redox density of states brought about by the molecule. The obtained results
      provide unique clues to single-molecule transport behavior and support the
      concept of single-molecule electrochemical gating.

PMID- 23546677
TI  - Intracellular delivery of biologically active proteins with peptide-based
      carriers.
AB  - The medical applications of protein-based therapeutics are hampered by low
      bioavailability associated with inefficient intracellular delivery. Various
      delivery materials have been developed and tested to interact with protein cargos
      in a manner of stabilizing proteins extracellularly and facilitating cellular
      uptake of proteins, thus enhancing delivery efficiency. Peptides that can form
      stable complexes with proteins through non-covalent interaction appear to be a
      promising tool to improve intracellular delivery of proteins. Here we describe
      the preparation of complexes formed between beta-galactosidase and peptide-based
      carrier, protein transfer of the complexes, and the methods to evaluate delivery
      efficiency qualitatively and quantitatively.

PMID- 23546678
TI  - Lipo-oligoarginine-based intracellular delivery.
AB  - Efficient cellular delivery, including plasma membrane permeability and
      intracellular metabolic stability, is a crucial factor determining the success of
      therapeutic agents. Cell-penetrating peptides (CPPs) have been widely used for
      the intracellular delivery of various bioactive molecules into cells to modify
      cellular functions. We have developed an improved CPP-based cellular delivery
      vector, named lipo-oligoarginine peptide (LOAP), by conjugating an oligoarginine
      peptide with a fatty acid moiety. The prepared LOAPs were further stabilized by
      introducing different combinations of D-Arg residues into the peptide backbone
      and were systematically evaluated for their membrane-penetrating properties and
      metabolic stabilities in cells.

PMID- 23546679
TI  - Fluorescent spherical monodisperse silica core-shell nanoparticles with a protein
      binding biofunctional shell.
AB  - The production of uniform protein-binding biofunctional fluorescent spherical
      silica core-shell nanoparticles by a modified Stober method is described.
      Fluorescent particle cores with diameters of 100 nm are synthesized in a two-step
      reaction. Functional shells for subsequent coupling reactions are provided by
      generating organic shells providing amine and carboxyl groups at the
      nanoparticles' shell surface. Conjugation of proteins to the nanoparticles is
      achieved using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)
      as coupling agent. The characterization of the nanoparticle systems and their
      surface functionalization is done by microelectrophoresis, dynamic light
      scattering (DLS), and a colorimetric detection of the amount of nanoparticle
      attached protein via a bicinchoninic acid (BCA) assay. Fluorescently spiked
      nanoparticle cores with biofunctional shells for molecular recognition reactions
      may be used as imaging tools or reporter systems.

PMID- 23546680
TI  - Direct quantification of PTD transduction using real-time monitoring.
AB  - Protein transduction domains (PTD or cell-permeable proteins) have attracted much
      attention as drug carriers because of their ability to penetrate cellular
      membranes. Although numerous PTD have been identified and their properties
      elucidated, their mechanism of action has not been fully understood due to the
      absence of a reliable quantification method. This chapter provides a direct
      method for quantifying cellular transduction of PTD in vitro and in vivo using
      bioluminescence imaging (BLI). This methodology exploits noninvasive techniques
      to create an environment suitable for the real-time imaging of PTD transduction
      and is therefore a promising tool for studying the mechanism of PTD transduction
      and the in vivo application of new therapeutic candidates.

PMID- 23546681
TI  - Genotoxic assessment of carbon nanotubes.
AB  - Carbon nanotubes are unique one-dimensional macromolecules with promising
      application in biology and medicine. Since their toxicity is still under debate,
      here we describe an investigation of genotoxic properties of purified single
      walled carbon nanotubes (SWCNT), multiwall carbon nanotubes (MWCNT), and amide
      functionalized purified SWCNT. We used two different cell systems: cultured human
      lymphocytes where we employed cytokinesis-block micronucleus test and human
      fibroblasts where we investigate the induction of DNA double-strand breaks (DSBs)
      employing H2AX phosphorylation assay.

PMID- 23546682
TI  - Separation science: Principles and applications for the analysis of
      bionanoparticles by asymmetrical flow field-flow fractionation (AF4).
AB  - Field-flow fractionation is an analytical technique that allows the separation of
      particles over a size range, from a few nanometers to several microns in
      diameter. The separation takes place under mild conditions and is suited for the
      analysis of neutral or charged particles. A single measurement yields the size
      and concentration of each component of a mixture. However, developing a suitable
      fractionation method can be tedious and time-consuming. In this chapter, we
      present asymmetrical flow field-flow fractionation (AF4) conditions that have
      proven their reliability for the analysis of quantum dots and other nanoparticles
      in the 5-50 nm size range. Common pitfalls are emphasized together with
      strategies to overcome them.

PMID- 23546683
TI  - Polymersomes-mediated delivery of fluorescent probes for targeted and long-term
      imaging in live cell microscopy.
AB  - Fluorescent microscopy becomes an essential tool for live imaging analysis of
      complex biological pathways and events as it enables noninvasive real-time/real
      space imaging. The design of fluorescent probes to provide dynamic information
      and long-term tracking of samples without altering physiological and structural
      integrity is critical in live imaging. In recent years, nanotechnology has
      produced a new generation of imaging probes with promising applications in live
      imaging. In particular, we describe the use of pH-sensitive amphiphilic block
      copolymer PMPC25-PDPA70. This polymer forms biomimetic nanometer-sized vesicles
      (known as polymersomes) that are readily uptaken by a wide variety of cell types.
      The pH sensitivity confers much needed endolysomal escape capability without
      inducing cellular toxicity or stress. Two different characteristic compartments
      in the polymersomes (hydrophilic core and hydrophobic membrane) allow for
      encapsulation of different labeling cargoes such as lipidic cell membrane probes,
      quantum dots, fluorescent dyes, and fluorescent biomolecules such as nucleic acid
      and protein probes.

PMID- 23546684
TI  - Protocol for the preparation of stimuli-responsive gold nanoparticles capped with
      elastin-based pentapeptides.
AB  - Stimuli-responsive materials are playing an increasingly important role in a wide
      range of applications such as drug delivery, diagnostics, sensors, and tissue
      engineering. Among them, gold nanoparticles responding to changes in their
      surrounding environment are of particular interest due to their size-related
      optical properties. Here, we present a novel strategy for the preparation of gold
      nanoparticles exhibiting a stimuli-responsive behavior. We rely on the use of a
      ligand consisting of only a single repeat of the elastin-based pentapeptide
      VPGVG. In this contribution, we describe a protocol for the solid-phase peptide
      synthesis of thiol-terminated VPGVG ligand, and for the preparation of gold
      nanoparticles covered with the pentapeptide through a ligand-exchange reaction.

PMID- 23546685
TI  - A novel adipocytokine, omentin, inhibits agonists-induced increases of blood
      pressure in rats.
AB  - Omentin is a recently identified adipocytokine, and we previously demonstrated
      that omentin played anti-inflammatory roles in vascular endothelial and smooth
      muscle cells. We also demonstrated that omentin induced vasodilation in rat
      isolated blood vessels. However, effects of omentin on blood pressure (BP) are
      not determined. Here, we examined whether intravenously injected omentin acutely
      alters BP of Wistar rats. Omentin (0.06-18 MUg/kg) alone did not alter BP of
      Wistar rats. On the other hand, omentin (18 MUg/kg) significantly inhibited
      noradrenaline (NA; 2 MUg/kg)-induced increases in systolic BP and mean BP.
      Omentin (18 MUg/kg) significantly inhibited angiotensin II (1 MUg/kg)-induced
      increases in diastolic BP. Omentin (18 MUg/kg) significantly inhibited
      dimorpholamine (3 mg/kg)-induced increases in diastolic BP. Omentin (18 MUg/kg)
      failed to inhibit the NA (0.02-2 MUg/kg)-induced increases of systolic BP in the
      nitric oxide (NO) synthase inhibitor, N(G)-nitro-l-arginine methyl ester (80
      mg/kg, 1 day)-treated Wistar rats. In summary, we for the first time demonstrated
      that omentin inhibited agonists-induced increases in BP. The effect of omentin
      was suggested to be mediated likely via NO-dependent mechanism. 

PMID- 23546686
TI  - Atypical canine mammary adenoma characterized by cystic ducts comprising a single
      layer of basaloid cells with myoepithelial differentiation.
AB  - This report describes an atypical mammary adenoma with a rare histological
      feature characterized by proliferating single-layered cystic ducts composed of
      basaloid cells with frequent myoepithelial differentiation. A 9-year-old, intact
      female Miniature Pinscher dog had mammary tumors on the thorax. Histologically,
      one of tumors comprised the proliferation of two types of tubular structures; the
      single-layered cystic ducts lined by flattened cells and double-layered tubules
      with luminal cells and outer spindle cells. The former ducts were predominant in
      the tumor and contained pale basophilic mucus, which was Alcian blue (pH 2.5)
      positive, but periodic acid Schiff-negative. Immunohistochemical staining
      indicated that the cells lining single-layered cystic ducts were negative for the
      luminal epithelial marker, cytokeratin (CK) CAM5.2, but were constantly positive
      for basal cell markers CK14 and p63 and frequently positive for SMA. Electron
      microscopy revealed fine, parallel myofilaments within these single-layered
      neoplastic cells. These histological and immunohistological examinations
      suggested that the origin of the tumor was bipotential mammary progenitor cells
      with predominant differentiation into the myoepithelial progenitor linage. 

PMID- 23546687
TI  - Organochlorine pesticides in squamate reptiles from southern Arizona, USA.
AB  - Despite recognition of the lack of reptile ecotoxicology data, the taxon remains
      poorly studied. Contaminant body burdens are useful in demonstrating exposures to
      contaminants do occur and may provide insight regarding risks. The purpose of
      this study was to determine organochlorine pesticide burdens in various tissues
      of terrestrial reptiles opportunistically collected in Arizona. Heptachlor, DDE,
      and endrin were the most common analytes detected in fat samples. Liver samples
      contained methoxychlor and heptachlor at greater frequency than other
      organochlorines. Investigations into chronic low-level exposures are rare for
      reptiles and research is needed to determine critical body residues associated
      with adverse impacts.

PMID- 23546688
TI  - Therapeutic potential of SIGIRR in systemic lupus erythematosus.
AB  - Single immunoglobulin IL-1-related receptor (SIGIRR), which is also known as
      Toll/interleukin-1 receptor 8, is a member of the interleukin-1 receptor (IL-1R)
      family. Different from other typical IL-1R superfamily members, SIGIRR seems to
      exert negatively modulates in immune responses. Several previous studies
      demonstrated that SIGIRR influences chronic inflammatory or autoimmune diseases,
      such as intestinal inflammation, rheumatoid arthritis and psoriatic arthritis.
      Recent work has explored the role of SIGIRR in systemic lupus erythematosus
      (SLE), for example, the role of SIGIRR protects the mice from hydrocarbon oil
      induced lupus has been reported. These results indicate that SIGIRR may represent
      a novel target for the treatment of SLE. In this review, we will discuss the
      SIGIRR and the therapeutic potential of modulating the pathway in SLE. 

PMID- 23546689
TI  - An increase in height of spinous process is associated with decreased heights of
      intervertebral disc and vertebral body in the degenerative process of lumbar
      spine.
AB  - PURPOSE: Currently degeneration of the intervertebral disc and joint in the
      degenerative process of the lumbar spine has mainly attracted the attention,
      however, there are very few literatures focusing on the height of the spinous
      process. Our objective was to examine in what generation the change in spinous
      process height occurs and how the change is involved in the degenerative process
      of the lumbar spine. METHODS: CT or CT myelography of 1,015 patients, 536 males
      and 579 females were measured in 6 items, including the heights of the L4 and L5
      vertebral bodies, the L4 and L5 spinous processes, the L4/5 intervertebral disc,
      and the L5/S1 intervertebral disc. All data of the 6 items were analyzed and
      compared between gender in 5 age groups (40s, 50s, 60s, 70s and 80s). RESULTS:
      The results indicated a significant increase in the height of the L4 and L5
      spinous process (P < 0.01) in the 60- to 70-year-old group for both genders, and
      also showed that the L4 and L5 vertebral body height was significantly decreased
      in the 50- to 60-year-old group (P < 0.01 in males, P < 0.001 in females).
      CONCLUSIONS: Changes in the spinous process morphology followed degenerative
      changes of the intervertebral disc and vertebral body in the degenerative process
      of the lumbar spine. This result may suggest that the morphological change of an
      increase in the height of the spinous process may be a kind of biological defense
      reaction to stabilize the intervertebral portion.

PMID- 23546691
TI  - A mental health clinician's view of cultural competence training.

PMID- 23546690
TI  - Sex- and age-dependent DNA methylation at the 17q12-q21 locus associated with
      childhood asthma.
AB  - Chromosomal region 17q12-q21 is one of the best-replicated genome-wide
      association study (GWAS) hits and associated with childhood-onset asthma.
      However, the mechanism by which the genetic association is restricted to
      childhood-onset disease is unclear. During childhood, more boys than girls
      develop asthma. Therefore, we tested the hypothesis that the 17q12-q21 genetic
      association was sex-specific. Indeed, a TDT test showed that in the Saguenay-Lac
      Saint-Jean familial collection, the 17q12-q21 association was significant among
      male, but not among female asthmatic subjects. We next hypothesized that the bias
      in the genetic association resulted from sex-specific and/or age-dependent DNA
      methylation at regulatory regions and determined the methylation profiles of five
      17q12-q21 gene promoters using the bisulfite sequencing methylation assay. We
      identified a single regulatory region within the zona pellucida binding protein 2
      (ZPBP2) gene, which showed statistically significant differences between males
      and females with respect to DNA methylation. DNA methylation also varied with age
      and was higher in adult males compared to boys. We have recently identified two
      functionally important polymorphisms, both within the ZPBP2 gene that influence
      expression levels of neighboring genes. Combined with the results of the present
      work, these data converge pointing to the same 5 kb region within the ZPBP2 gene
      as a critical region for both gene expression regulation and predisposition to
      asthma. Our data show that sex- and age-dependent DNA methylation may act as a
      modifier of genetic effects and influence the results of genetic association
      studies.

PMID- 23546692
TI  - Lateral migration of flexible fibers in Poiseuille flow between two parallel
      planar solid walls.
AB  - Dynamics of non-Brownian flexible fibers in Poiseuille flow between two parallel
      planar solid walls is evaluated from the Stokes equations which are solved
      numerically by the multipole method. Fibers migrate towards a critical distance
      from the wall zc, which depends significantly on the fiber length N and bending
      stiffness A. This effect can be used to sort fibers. Three types of accumulation
      are found, depending on a shear-to-bending parameter Gamma. In the first type,
      stiff fibers deform only a little and accumulate close to the wall, where their
      tendency to drift away from the channel is balanced by the repulsive hydrodynamic
      interaction with the wall. In the second type, flexible fibers deform
      significantly and accumulate far from the wall. In both types, the fiber shapes
      at the accumulation positions are repeatable, while in the third type, they are
      very compact and non-repeatable. The difference between the second and third
      accumulation types is a special case of the difference between the regular and
      irregular modes for the dynamics of migrating fibers. At the regular mode, far
      from walls, the fiber tumbling frequency satisfies Jeffery's expression, with the
      local shear rate and the aspect ratio close to N.

PMID- 23546693
TI  - Confined flows of a polymer microgel.
AB  - In this paper, we probe the influence of confinement on the flows of a polymer
      microgel, namely Carbopol. We compare its bulk rheological behavior, measured
      with a rheometer and well described by a Hershel-Bulkley law, to velocity
      profiles measured in rough microchannels, obtained with a particle tracking
      velocimetry technique. We show a strong disagreement between the bulk prediction
      for the velocity profiles and the measured ones in the microchannels. Velocity
      profiles in confined conditions are successfully analyzed within the framework of
      a non-local fluidity model introduced recently (J. Goyon et al. Nature, 454, 84
      (2008)). This allows to determine a cooperativity length xi, whose order of
      magnitude compares with the structure size of the microgel. Moreover, we measure
      flow curves using a rheometer for different gap conditions and also show that
      this set of data exhibit a strong effect of the confinement on the measured
      rheological properties. This is again characterized by a typical length of the
      same order as the cooperativity length scale xi. We thus evidence confinement
      effects with two complementary experiments which both give the same typical
      length for the rearrangements in the flows.

PMID- 23546698
TI  - Preventive saline irrigation of the bile duct after the endoscopic removal of
      common bile duct stones.
AB  - BACKGROUND: Small stone fragments after an endoscopic stone extraction for
      choledocholithiasis may act as the nidus for recurrent choledocholithiasis.
      Therefore, efforts to eliminate the nidus might reduce the recurrence of
      choledocholithiasis and cholangitis related to choledocholithiasis. AIMS: The
      purpose of this study was to determine whether an additional preventive saline
      irrigation of the bile duct after the endoscopic removal of common bile duct
      stones would decrease residual stones and the recurrence of cholangitis. METHODS:
      A retrospective analysis was performed for the consecutively collected data about
      the patients who underwent the complete endoscopic treatment for common bile duct
      stone. RESULTS: Among 99 patients, 45 patients underwent saline irrigation.
      Residual stones were detected in 18 patients (18.2 %). The incidences of residual
      stones were 8.9 % (4 of 45 patients) in the irrigation group and 25.9 % (14 of 54
      patients) in the non-irrigation group (P = 0.037). In multivariate analysis,
      preventive saline irrigation was found to be the only significant factor for the
      decrease of residual stones (HR = 0.258, P = 0.039). When analyzing the
      occurrence of recurrent cholangitis and the procedure related to complications,
      there were no significant differences according to the performance of preventive
      saline irrigation of the bile duct. CONCLUSIONS: Preventive saline irrigation
      could reduce the residual common bile duct stones without complications.

PMID- 23546699
TI  - For biliary dilatation, a negative endosonography needs additional image studies
      in weight loss suggesting malignancy.
AB  - BACKGROUND AND AIM: Biliary dilatation frequently raises concerns about the
      possibility of pancreatobiliary diseases. This study assessed the etiologic yield
      of endosonography (EUS) in this situation. METHODS: A retrospective review was
      completed with 163 consecutive patients who had undergone EUS for a dilated
      common bile duct (CBD) without definite pathology on ultrasonography. RESULTS:
      Binary logistic regression analysis disclosed that malignancy was positively
      related to weight loss and was inversely related to abdominal pain; nevertheless,
      choledocholithiasis was positively related to fever and elevated carbohydrate
      antigen 19-9 (p < 0.05). The accuracy of EUS was 95.1 % (155/163) for overall
      cause of biliary dilatation, 100 % (73/73) for no pathological finding, 96.3 %
      (26/27) for ampullary cancer, 84.6 % (11/13) for pancreatic cancer, 40.0 % (2/5)
      for CBD cancer, and 92.6 % (25/27) for choledocholithiasis, respectively. The
      accuracy of EUS decreased in the presence of malignancy (86.7 %, 39/45 vs. 98.3
      %, 116/118, p = 0.006). EUS missed three CBD cancers, two pancreatic cancers, and
      one ampullary cancer; however, the diagnosis was rescued by computed tomography
      in two pancreatic cancers and one CBD cancer. CONCLUSIONS: EUS is accurate in
      patients with fever suggestive of choledocholithiasis. However, a negative EUS
      finding should call for additional image studies in patients with weight loss
      suggestive of malignancy.

PMID- 23546700
TI  - The prevalence and clinical correlates of nonalcoholic fatty liver disease
      (NAFLD) in African Americans: the multiethnic study of atherosclerosis (MESA).
AB  - BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the number one
      cause of liver disease in the United States. The prevalence rates in African
      Americans (AA), while significantly lower than other ethnic groups with similar
      known risk factors, have been quoted as high as 24 %. We aim to determine if the
      presence of NAFLD in African Americans is associated with lower triglyceride
      and/or higher HDL-c levels and if NAFLD risk factors in African Americans differ
      from other ethnic groups. METHODS: A total of 3,056 participants of the Multi
      Ethnic Study of Atherosclerosis were included in this study. We utilized the
      baseline serum, anthropometric and radiographic measurements obtained between
      2000 and 2002. NAFLD was defined as liver spleen ratio <1 from CT measurements.
      RESULTS: The prevalence of NAFLD was and 11 % in AA. We found that age,
      education, triglyceride levels, HDL-c levels, waist circumference and HOMA-IR
      were independent correlates of NAFLD in this population. Among those with NAFLD,
      AA had significantly lower triglyceride levels than Hispanics [125 mg/dl (95 % CI
      107-143) versus 192 mg/dl (95 % CI 169-215), p < 0.001] and Caucasians [185 mg/dl
      (95 % CI 161-209), p = 0.001]. Serum HDL-c was significantly higher in AA with
      NAFLD (47 mg/dl; 95 % CI 45-50) when compared to Hispanics (44 mg/dl; 95 % CI 43
      66, p = 0.02) and Caucasians (44 mg/dl; 95 % CI 42-46, p = 0.02) with NAFLD.
      CONCLUSIONS: This study demonstrated that the clinical correlates of NAFLD in
      African Americans are similar to the correlates of NAFLD in other ethnic groups.
      Our data also suggests that when evaluating African Americans for NAFLD risk,
      lower cutoff values should be used to define abnormal triglyceride levels.

PMID- 23546701
TI  - The coagulation system in humans.
AB  - Complex, interrelated systems exist to maintain the fluidity of the blood in the
      vascular system while allowing for the rapid formation of a solid blood clot to
      prevent hemorrhaging subsequent to blood vessel injury. These interrelated
      systems are collectively referred to as haemostasis. The components involved in
      the haemostatic mechanism consist of vessel walls, platelets, coagulation
      factors, inhibitors, and the fibrinolytic system. In the broadest sense, a series
      of cascades involving coagulation proteins and enzymes, as well as cell surfaces
      (platelets and endothelial cells), work together to generate thrombin, the key
      enzyme in coagulation, subsequently leading to the formation of a fibrin clot.
      However, there also exist direct and indirect inhibitors of thrombin to ensure
      that clot formation does not go uncontrolled. Once the fibrin clot is formed, the
      fibrinolytic system ensures that the clot is lysed so that it does not become a
      pathological complication. Taken together, the systems exist to balance each
      other and maintain order. The balance of coagulation and fibrinolysis keeps the
      haemostatic system functioning efficiently.

PMID- 23546702
TI  - Platelet physiology.
AB  - Platelets are cell fragments which circulate in blood. They are of pivotal
      importance in blood clot formation, affecting thrombosis and haemostasis. By
      rapidly altering the activation and expression of surface receptors, platelets
      are able to quickly undergo structural and phenotypic changes in response to
      stimulation, such as collagen exposure on injured vascular endothelium. This
      response to stimulation allows platelets to become adhesive, aggregate to form a
      thrombus, and release a variety of mediators affecting coagulation, inflammation,
      and chemotaxis at the site of injury. Therefore, in addition to their critical
      role in thrombosis and haemostasis, platelets also play a role in immunity,
      inflammation, wound healing, haematologic malignancies, and metabolic disorders.
      The role of platelets in disease, particularly in atherothrombosis, is
      increasingly the focus of current research and antiplatelet therapy plays a
      significant role in the prevention and treatment of atherothrombotic and
      inflammatory diseases.

PMID- 23546703
TI  - The role of the vessel wall.
AB  - The role of the vessel wall is complex and its effects are wide-ranging. The
      vessel wall, specifically the endothelial monolayer that lines the inner lumen,
      possesses the ability to influence various physiological states both locally and
      systemically by controlling vascular tone, basement membrane component synthesis,
      angiogenesis, haemostatic properties, and immunogenicity. This is an overview of
      the function and structure of the vessel wall and how disruption and dysfunction
      in any of these regulatory roles can lead to disease states.

PMID- 23546704
TI  - Specimen requirements for the haemostasis laboratory.
AB  - Sample integrity is one of the most important details to consider for the
      production of quality results in the laboratory. Many factors have the potential
      to adversely affect the sample: intrinsic patient characteristics (caused by the
      underlying malady and/or treatment, incorrect patient preparation, etc.),
      difficult or incorrectly performed collection of sample, correct timing of sample
      collection relative to drug administration, incorrect processing and transport
      within the laboratory-just to name a few. This chapter outlines standard common
      requirements with explanations as a basis for those limitations, and practical
      laboratory advice to attain and maintain dependable samples.

PMID- 23546705
TI  - Methods of coagulation.
AB  - The investigation of haemostasis is aimed to replicate normal blood coagulation
      in the laboratory. There are a number of different methods employed including
      clot-based coagulation tests, chromogenic assays, immunological tests, and
      aggregation studies. Today automated machines are designed to be able to perform
      a number of different methodologies. To guarantee the results produced by a
      laboratory are reliable and accurate, laboratories need to follow international
      standards and guidelines and use established methodologies. The laboratory needs
      a quality management plan, to perform internal quality control and participate in
      an external quality assurance program.

PMID- 23546706
TI  - Reference ranges of coagulation tests.
AB  - Reference ranges are a set of values that correctly include most of the subjects
      with characteristics similar to the reference group and exclude the others. When
      accurate, reference ranges aid physicians to interpret results of clinical
      measurements and thus establish diagnosis. However, obtaining accurate reference
      ranges is a very demanding procedure. This chapter provides basic definitions and
      theories as well as a step-by-step procedure for the analysis of reference values
      and determination of reference ranges of coagulation, focusing on quantitative
      clinical laboratory assays. Preanalytical and analytical factors as well as
      dependence on the age influencing reference values for coagulation assays and
      their transference are discussed.

PMID- 23546708
TI  - Activated partial thromboplastin time.
AB  - Activated partial thromboplastin time (APTT) is a commonly used coagulation assay
      that is easy to perform, is affordable, and is therefore performed in most
      coagulation laboratories, both clinical and research, worldwide. The APTT is
      based on the principle that in citrated plasma, the addition of a platelet
      substitute, factor XII activator, and CaCl2 allows for formation of a stable
      clot. The time required for the formation of a stable clot is recorded in seconds
      and represents the actual APTT result.

PMID- 23546707
TI  - Lupus anticoagulant testing.
AB  - Antiphospholipid antibodies are a heterogenous group of autoantibodies directed
      against glycoproteins in concert with anionic phospholipids. In clinical
      laboratory practice, antiphospholipid antibody evaluations usually consist of a
      combination of the following: anticardiolipin antibody assay, anti-beta 2
      glycoprotein I assay, and at least two lupus anticoagulant assays with an
      appropriate confirmatory test. Lupus anticoagulants produce their laboratory
      effect by prolonging recalcification times in assays within which phospholipid
      content is limited. Although many assays are available, all are based on the
      fundamental principle of demonstrating normalization of prolonged recalcification
      times with the addition of exogenous phospholipid. The antibody specificity of an
      individual lupus anticoagulant is difficult or impossible to determine; however a
      small proportion do demonstrate avidity for selected proteins such as prothrombin
      or beta 2 glycoprotein I. The mechanism by which these antibodies cause their
      clinical manifestations remains unknown; however their relationship to increased
      risk of thrombosis, pregnancy loss, and autoimmune thrombocytopenia is undoubted.
      There is no correlation between the "strength" of lupus anticoagulants and the
      level of thrombotic risk; thus it is important to identify both "weak" and
      "strong" lupus anticoagulants.

PMID- 23546709
TI  - Prothrombin time/international normalized ratio.
AB  - Prothrombin time (PT) and/or International Normalized Ratio (INR) is the most
      commonly used coagulation assay in health care, to diagnose the risk of bleeding
      and to monitor oral anticoagulation therapy. This test is based on the principle
      that in citrated plasma, the addition of a thromboplastin and CaCl2 allows for
      formation of a stable clot. The time required for the formation of a stable clot
      is recorded in seconds and represents the actual PT result. INR is calculated
      from the PT and allows for worldwide standardization of results.

PMID- 23546710
TI  - Thrombin clotting time.
AB  - Thrombin clotting time (TCT) is a coagulation assay used to diagnose congenital
      and acquired fibrinogen deficiency (Adcock et al., Coagulation handbook, Esoterix
      Coagulation, Austin, TX, 2002), as well as to identify contamination by heparin,
      prior to performing additional coagulation assays. This test is based on the
      principle that in citrated plasma, the addition of Thrombin allows for formation
      of a stable clot. The time required for the formation of a stable clot is
      recorded in seconds and represents the actual TCT result.

PMID- 23546711
TI  - Thrombin generation.
AB  - Generation of thrombin has been established as the critical process leading to
      coagulation in vivo. Indeed, ex vivo markers of thrombin generation in patients
      have been useful in detecting thrombosis, while many standard global clot-time
      tests of haemostasis in blood or plasma samples are simple endpoint measures of
      the potential to generate thrombin. Thus, there has been a recent surge towards
      direct measurement of thrombin generation potential in plasma/blood samples as a
      refined methodology for more precisely assessing
      procoagulant/anticoagulant/hemorrhagic parameters of the haemostatic status.
      Presently, however, there is no consensus method for thrombin generation
      determination. The present treatise gives detailed procedures for available
      thrombin generation tests, with emphasis on the preferred technology.

PMID- 23546712
TI  - Activated clotting time (ACT).
AB  - The standard assay for monitoring anticoagulation during extracorporeal life
      support (ECLS) is the activated clotting time (ACT) test, with celite, kaolin,
      and glass beads being the most commonly used activators to initiate contact
      activation. The point-of-care ACT test has been the preferred test in
      catheterization labs and cardiac theatres because it has a number of advantages
      over laboratory tests (Spinler et al., Ann Pharmacother 39(7-8):1275-1285, 2005):
      Shorter time between sampling and results. Smaller blood sample size.
      Availability to have test performed by non-lab personnel. Reduced errors
      associated with sample mislabeling/mishandling. Decreased risk of sample
      degradation with time. There are other coagulation monitoring tests available;
      however these are usually specific and do not take into account the global
      picture of the entire clotting system. The standard coagulation tests
      (prothrombin time (PT), activated partial thromboplastin time, thrombin time
      (TT), and fibrinogen level) are plasma tests measuring plasma haemostasis and not
      patient haemostasis. The ACT measurement uses whole blood, thereby incorporating
      the importance of platelets and phospholipids in the role of coagulation. Many of
      the problems with the haemostatic system during ECLS are caused by the activation
      of platelets, which are not detected by standard tests. Because an ACT test is
      nonspecific there are many variables such as hypothermia, platelets, aprotinin,
      GP IIb/IIIa antagonists, haemodilution, etc. that can alter its results. For this
      reason it is important to gain an understanding as to how these variables
      interact for meaningful interpretation of the ACT test result.

PMID- 23546713
TI  - Factor XIII assays.
AB  - Factor XIII (FXIII) deficiency is a rare cause of bleeding and pregnancy loss
      that is easily treated with plasma products. Reliable assays for FXIII are
      necessary not only for the diagnosis of deficiency state but also to guide
      prophylaxis and replacement therapy in patients during times of increased risk.
      Diagnostic tests for FXIII activity whilst not technically demanding have a
      number of pitfalls including limited sensitivity and overestimation of activity
      at the lower end. Despite these shortcomings the performance of these assays is
      adequate for the diagnosis and management of the majority of patients with
      clinically significant deficiency.

PMID- 23546715
TI  - Platelet counting.
AB  - Platelet counting is a daily basic hematological analysis of crucial interest in
      many clinical situations. Historical manual techniques (phase-contrast
      microscopy) have been replaced by automated techniques (impedance or optical
      analyzers) more rapid and precise. More recently, flow cytometry techniques using
      labeled monoclonal antibodies have been proposed as reference techniques.
      Nevertheless, pre-analytical and analytical variables should be respected to
      obtain reliable results and avoid validation pitfalls.

PMID- 23546714
TI  - Fibrinogen.
AB  - Fibrinogen is the final essential building block of the clotting process. Thus,
      all of the preliminary "cause and effect" events in the clotting cascade rely on
      the work of this molecule to measure their success. The most commonly used
      laboratory method for measuring fibrinogen is the Clauss fibrinogen assay. The
      Clauss fibrinogen assay is a quantitative, clot-based, functional assay. The
      assay measures the ability of fibrinogen to form fibrin clot after being exposed
      to a high concentration of purified thrombin. Plasma samples are pre-diluted
      which minimize assay interference from substances like heparin and fibrinogen
      degradation products. In brief, the diluted plasma is incubated at 37 degrees C
      prior to the addition of the pre-warmed (37 degrees C) thrombin reagent. From the
      exact moment of the addition of thrombin, the time to clot is measured. The
      clotting time in seconds is interpolated from a standard curve made using various
      dilutions of assayed standard plasma. The following chapter includes detailed
      information on the Clauss fibrinogen assay. Other fibrinogen assays used include
      fibrinogen levels derived from prothrombin time assays and antigenic methods.
      Fibrinogen measurements using the prothrombin time and antigenic based assays are
      described in brief.

PMID- 23546716
TI  - Platelet morphology analysis.
AB  - Platelets are very small blood cells (1.5-3 MUm), which play a major role in
      primary haemostasis and in coagulation mechanisms. Platelet characterization
      requires their counting (see Chapter 15 ) associated with accurate morphology
      analysis. We describe the major steps in order to correctly obtain stained blood
      films, which can be analyzed by optical microscope. Platelet morphology
      abnormalities are found in acquired malignant hematological diseases such
      myeloproliferative or myelodysplastic syndromes and acute megakaryoblastic
      leukemia. A careful analysis of the platelet size and morphology, by detecting
      either normal platelets with or without excessive anisocytosis, microplatelets,
      or large/giant platelets, will contribute to inherited thrombocytopenia diagnosis
      and gather substantial data when looking for an acquired platelet disorders.

PMID- 23546717
TI  - Light transmission aggregometry.
AB  - Laboratory testing of platelet function is essential for the diagnosis of several
      congenital and acquired platelet disorders. Moreover, it is increasingly being
      utilized to monitor the efficacy of antiplatelet therapy. Light transmission
      platelet aggregation is the most useful in vitro test of platelet function
      currently available, and it is still the gold standard to detect platelet
      disorders and to initiate a more precise characterization.

PMID- 23546718
TI  - Platelet flow cytometry.
AB  - Flow cytometry is a powerful and versatile tool which can be used to provide
      substantial phenotypic data on platelets by yielding quantitative information of
      their physical and antigenic properties. This includes surface expression of
      functional receptors, bound ligands, expression of granule components,
      interaction of platelets with other platelets via aggregation, or interaction
      with other blood components, such as leukocytes or the plasma coagulation system.
      Quantitative assessment of these parameters may facilitate the diagnosis of
      inherited or acquired platelet disorders, assist in the diagnosis of diseases
      associated with platelet activation, or assist in the monitoring of safety and
      efficacy of antiplatelet therapy.

PMID- 23546719
TI  - Anti-factor Xa (anti-Xa) assay.
AB  - The anti-factor Xa (anti-Xa) assay is a functional assay that facilitates the
      measurement of antithrombin (AT)-catalyzed inhibition of factor Xa by
      unfractionated heparin (UFH) and direct inhibition of factor Xa by low-molecular
      weight heparin (LMWH) (Kitchen, Br J Haematol 111:397-406, 2000; Walenga et al.,
      Semin Thromb Hemost 11:17-25, 1985; Levine et al., Arch Intern Med 154:49-56,
      1994; Barrowcliffe et al., J Pharm Biomed Anal 7:217-226, 1989; Triplett, Ther
      Drug Monit 1:173-197, 1979; Nelson, Clin Lab Sci 12:359-364, 1999; Laffan and
      Manning, Dacie and Lewis: practical haematology, Churchill Livingstone, London,
      pp 465-479, 2001; Olson et al., Arch Pathol Lab Med 122:782-798, 1998). Whilst
      automated methods for the determination of the abilities of UFH and LMWH to
      inhibit factor Xa have been available since the 1970s, their cost was viewed to
      prohibit their broad use in the clinical management of UFH and LMWH until
      relatively recently. The anti-Xa assay can also be used to guide the
      determination of therapeutic APTT ranges in the clinical management of UFH (Hirsh
      and Raschke, Chest 126:188S-203S, 2004). As a result, the anti-Xa assay is
      commonly viewed as a heparin assay, despite the fact that it actually provides a
      measure of UFH effect as opposed to a measure of UFH concentration.

PMID- 23546720
TI  - Reptilase time (RT).
AB  - The reptilase time is a functional plasma clotting assay, which is based on the
      enzymatic activity of batroxobin. By specifically cleaving fibrinogen A from
      fibrinogen, batroxobin leads to the formation of a stable fibrin clot. The time,
      starting from the addition of batroxobin to the plasma sample, until clot
      formation is the reptilase time and is given in seconds. Clot formation can be
      detected manually or on automated coagulation systems. Reference values for
      healthy adults are 18-22 s. Healthy newborns may have a slightly prolonged
      reptilase time of up to 24 s. In addition to other coagulation assays, the
      reptilase time is usually performed to confirm or to exclude the suspicion of
      dysfibrinogenemias. The reptilase time is independent of thrombin generation
      disturbances or disturbances in the action of thrombin on fibrinogen. Therefore,
      it can be used to confirm heparin contamination or to obtain similar information
      as with the thrombin clotting time in heparinized and hemophiliac patients.

PMID- 23546721
TI  - Protamine titration.
AB  - Protamine titration is the gold standard method for the measurement of
      unfractionated heparin (UFH) concentration in plasma. Protamine titration
      produces reliable and reproducible results; however it is -generally not
      considered a convenient assay for current clinical management of UFH as it is not
      readily automated (Olson et al. Arch Pathol Lab Med 122(9):782-798, 1998). Early
      clinical trials of UFH therapy determined that a heparin concentration of 0.2-0.4
      U/ml by protamine titration correlated to an APTT of 1.5-2.5 times higher
      compared to baseline values produced desirable UFH safety and efficacy outcomes
      (Hull et al. N Engl J Med 315(18):1109-1114, 1986; Hull et al. N Engl J Med
      322:1260-1264, 1990; Turpie et al. N Engl J Med 320:352-357, 1989; Brill-Edwards
      et al. Ann Intern Med 119(2):104-109, 1993; Hull Int Angiol 14(1):32-34, 1995).
      Such studies paved the way to the current view that it is no longer ideal to
      manage UFH based solely upon a 1.5-2.5 times prolongation of the "normal" APTT.
      Most advisory bodies recommend therapeutic APTTs be determined by correlating
      APTT results with therapeutic UFH levels as measured by anti-Xa assay (0.35-0.7
      U/ml) or protamine titration (0.2-0.4 U/ml) (Hirsh and Raschke. Chest 126(3):188S
      203S, 2004) (see Note 1). The concentration of UFH in a sample is measured by
      determining the amount of protamine required to return the thrombin clotting time
      (TCT) test (prolonged by UFH) to a pre-UFH level (Laffan and Manning. Dacie and
      Lewis: practical haematology. Churchill Livingstone: London, 2001).

PMID- 23546722
TI  - Laboratory methods for the assay of tissue factor pathway inhibitor in human
      plasma.
AB  - Tissue factor pathway inhibitor (TFPI) is being assayed with increasing frequency
      by researchers attempting to further understand the complexities of the
      coagulation system. There are a number of methods available for measurement of
      TFPI; however immunological measurement by ELIZA is the most common assay used.
      There are a number of commercial kits available for this assay and close
      attention to detail is critical for accurate results.

PMID- 23546723
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating
      immunoglobulin (Ig) G antibodies that recognize multimolecular complexes of
      platelet factor 4 (PF4) bound to heparin or other polyanions. Most laboratory
      assays for HIT have a high sensitivity for anti-PF4/heparin antibodies and a
      negative test generally excludes HIT (high negative predictive value), especially
      in a setting of a low pretest probability. The magnitude of a positive test
      result correlates with greater likelihood of HIT. Therefore, a combined
      diagnostic approach that considers the clinical picture and the magnitude of a
      positive test result is recommended for accurate diagnosis of HIT.

PMID- 23546724
TI  - Nijmegen-Bethesda assay to measure factor VIII inhibitors.
AB  - Hemophilia A is an inherited bleeding disorder caused by a deficiency of factor
      VIII coagulant activity (FVIII:C). Patients are treated with infusions of either
      plasma-derived or recombinant factor VIII. However, some patients develop
      inhibitory antibodies (inhibitors) to infused factor VIII which render it
      ineffective. The original Bethesda method was developed to standardize
      measurement of inhibitors in a factor VIII neutralization assay. One Bethesda
      unit is defined as that amount of inhibitor that results in 50% residual FVIII:C
      activity of a defined test mixture. In the Nijmegen modification of the original
      Bethesda method, the pH and the protein concentration of the test mixture is
      further standardized. As a result, the FVIII:C in the test mixture is less prone
      to artifactual deterioration and the test has improved specificity. Even with a
      standardized procedure a number of factors can affect the performance of the test
      and it is important for laboratory staff to be aware of their impact on the
      result outcome.

PMID- 23546725
TI  - Kaolin clotting time.
AB  - The kaolin clotting time (KCT) is a sensitive test used in the laboratory
      detection of lupus anticoagulants (LA) (Derksen and de Groot, Thromb Res 114:521
      526, 2004). It is essentially an activated partial thromboplastin time (APTT)
      test with no added phospholipid. Kaolin acts as the activator in the KCT. In the
      absence of additional phospholipid reagent, the quality of the test sample is
      extremely important since the generation of thrombin completely depends on the
      presence of residual cell membranes and plasma lipids (Derksen and de Groot,
      Thromb Res 114:521-526, 2004). Since the test contains no exogenous phospholipid,
      a confirmatory test using excess phospholipid is required to confirm the presence
      of lupus anticoagulant in the sample (Court, Br J Biomed Sci 54:287-298, 1997).

PMID- 23546726
TI  - The dilute Russell's viper venom time.
AB  - The dilute Russell's viper venom time is a clot-based test used in the detection
      of the lupus anticoagulant in the laboratory. Lupus anticoagulants and the
      overall approach for their detection are described in Chapter 7.

PMID- 23546727
TI  - Platelet neutralization test.
AB  - The platelet neutralization test is used in the laboratorvy diagnosis of the
      lupus anticoagulant (Laffan and Manning, Dacie and Lewis practical haematology.
      Churchill Livingstone, Philadelphia, PA, pp 445-446, 2006). The lupus
      anticoagulant typically causes prolongation of phospholipid-dependent coagulation
      tests such as APTT, DRVVT, etc. The phospholipid-dependent nature of the LA can
      be demonstrated by adding washed and "fractured" platelets as a source of
      phospholipid and repeating the tests. If an LA is present in the sample, the
      addition of platelets will correct the prolonged clotting times. This appears to
      be due to the ability of the platelets to absorb the LA and negate its effect on
      the clotting time (Br J Haematol 109:704-715, 2001).

PMID- 23546728
TI  - Antithrombin.
AB  - Antithrombin (AT) is a heparin cofactor and a member of the serine protease
      inhibitor family (serpin). The mature AT molecule is composed of 432 amino acids
      and it is produced mainly in the liver. Initially, several different AT
      activities in plasma were reported, leading to the classification of antithrombin
      in a range from I to IV. It was subsequently shown that these various
      antithrombin activities were the function of one molecule, antithrombin III,
      whose name was reduced to antithrombin at the meeting of the International
      Society in Thrombosis and Haemostasis in 1993. AT is an important protease
      inhibitor of thrombin and factor Xa. However, AT is also able to inhibit factors
      IXa, XIa, XIIab, kallikrein, and plasmin. Given that AT is one of the major
      naturally occurring inhibitors of coagulation, acquired or hereditary
      deficiencies of this protein result in excessive thrombin generation. As a vast
      array of mutations are responsible for hereditary AT deficiencies, screening for
      their presence by DNA testing would require sequencing each entire gene involving
      numerous exons. Moreover, the knowledge of the gene mutation does not offer any
      benefit in the treatment of affected families, so the routine molecular
      characterization is not indicative. These defects are detected by functional or
      immunological assays. AT amidolytic assays are recommended for initial testing
      for AT deficiency. There is no need to routinely perform AT immunological assays.
      However, they are useful in order to distinguish type I from type II hereditary
      AT deficiency.

PMID- 23546729
TI  - Protein C.
AB  - Protein C (PC) is a 62-kDa vitamin K-dependent plasma zymogen which, after
      activation to serine protease, plays an important role in the physiologic
      regulation of blood coagulation. Given that PC is one of the major naturally
      occurring inhibitors of coagulation, acquired or hereditary deficiencies of this
      protein result in excessive thrombin generation. As a vast array of mutations are
      responsible for hereditary PC deficiencies, screening for their presence by DNA
      testing would require sequencing each entire gene involving numerous exons.
      Moreover, the knowledge of the gene mutation does not offer any benefit in the
      treatment of thrombophilic families, so the routine molecular characterization is
      not indicative. These defects are detected by functional or immunological assays.
      Measurement of PC activity is essential to identify subjects with both type I and
      type II PC defects. There is no need to routinely perform PC immunological
      assays. However, they are useful in order to distinguish type I from type II PC
      hereditary deficiency.

PMID- 23546730
TI  - Protein S.
AB  - Protein S (PS) is a vitamin K-dependent plasma glycoprotein. Around 60-70% of PS
      in plasma is noncovalently bound to C4-binding protein (C4BP). Free PS functions
      as a cofactor that enhances the activity of activated protein C (APC) in the
      proteolytic degradation of activated factors V and VIII. PS also has a more
      recently described APC-independent ability to directly inhibit prothrombinase and
      tenase by direct binding of activated factors V, VIII, and X. Given that PS is
      one of the major naturally occurring inhibitors of coagulation, acquired or
      hereditary deficiencies of this protein result in excessive thrombin generation.
      As a vast array of mutations are responsible for hereditary PS deficiencies,
      screening for their presence by DNA testing would require sequencing each entire
      gene involving numerous exons. Moreover, the knowledge of the gene mutation does
      not offer any benefit in the treatment of thrombophilic families, so the routine
      molecular characterization is not indicative. These defects are detected by
      functional or immunological assays for free and total PS forms. Given that
      functional PS assays may detect some forms of PS deficiency that free PS
      immunoassays may miss, it is recommended to include them for initial testing
      along with immunoassays for free PS, although they should be used with caution.
      Functional PS assays are subject to multiple interference. For example in the
      presence of lupus anticoagulant (LA), only free PS immunoassays are recommended
      for initial testing. PS antigen assays are more popular with most laboratories.

PMID- 23546731
TI  - Testing for hyperhomocysteinemia in subjects with a history of thromboembolic
      events using HPLC technique.
AB  - An elevated homocysteine level is a well-known thrombophilic risk factor.
      Determination of total plasma homocysteine therefore is an integrated part of the
      diagnostic setting after thromboembolic events; about 5-7% of the population do
      have elevated homocysteine levels. Some forms of hyperhomocysteinemia are
      treatable; thus a standardized and reliable diagnostic setting has to be at hand.
      HPLC analysis is widely available in routine diagnostic laboratories. We use the
      fluorogenic reagent SBD-F to derivate with plasma homocysteine after release of
      the amino acid from homo- and heterodimers and protein bond using TBP. Separation
      is performed using a c18 reverse-phase column with aqua and acetonitrile as
      solvent. Due to continuous release of homocysteine from blood cells
      centrifugation and separation of plasma within 30 min after venous puncture are
      crucial for reproducible results.

PMID- 23546732
TI  - Anticardiolipin antibody and anti-beta 2 glycoprotein I antibody assays.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease and is a risk factor for
      a number of clinical manifestations; the classic presentations include fetal
      death or thrombosis (arterial or venous thromboembolism), in the presence of
      persistently increased titers of antiphospholipid (aPL) antibodies. The actual
      cause of APS is unknown but thought to be multifactorial. The disease is
      characterized by the presence of a heterogenous population of autoantibodies
      against phospholipid-binding proteins. APS presents either in isolation with no
      evidence of an underlying disease or in concert with an autoimmune disease such
      as systemic lupus erythematosus or rheumatoid arthritis. The wide diversity in
      clinical presentation often causes difficulty in identifying and treating
      patients and therefore a concise laboratory report containing interpretative
      comments is required to provide needed guidance to the clinician. For a diagnosis
      of APS to be made both clinical and laboratory classification criteria must be
      met. Laboratory testing to identify aPL antibodies includes lupus anticoagulant
      (liquid-based clotting assays) and immunological solid-phase assays (usually
      enzyme-linked immunosorbent assay formats) for IgG and/or IgM anticardiolipin
      (aCL) antibodies and anti-beta 2 glycoprotein I (beta2-GPI) antibodies. Other
      autoantibodies, such as those directed against anionic phospholipids, can also be
      assayed; however they are not of clinical significance. Participation in a
      quality assurance program and an in-depth technical and clinical understanding of
      testing for aPL antibodies are required, as methods are limited by poor
      robustness, reproducibility, specificity, and standardization. Testing is further
      complicated by the lack of a "gold standard" laboratory test to diagnose or
      classify a patient as having APS. This chapter discusses the clinical and
      laboratory theoretical and technical aspects of aCL and anti-beta2GPI antibody
      assays.

PMID- 23546734
TI  - D-dimer and fibrinogen/fibrin degradation products.
AB  - Although clinical requests for D-dimer are generally in the minority of assays in
      the routine clinical laboratory, they are an important aspect-especially if the
      laboratory supports an active emergency room and hematology service. Throughout
      the literature, D-dimer assays have been used for many purposes in the research
      setting; however it is generally the negative predictive value of the assay that
      is the most common piece of information being utilized from the standpoint of a
      clinician. Research or clinical needs will dictate the type of assay required-a
      qualitative, semiquantitative, or quantitative D-dimer assay may be appropriate
      for a particular purpose. Commonalities and differences between these assay types
      are outlined here, as well as universal concerns regarding standardization of D
      dimer assay results.

PMID- 23546733
TI  - Testing for apolipoprotein(a) phenotype using isoelectric focusing and
      immunoblotting technique.
AB  - Increased levels of lipoprotein(a) are known as an independent risk factor for
      atherosclerosis, heart disease, and stroke in man. Even in children it could show
      that elevated levels of Lp(a) are an independent thromboembolic risk factor.
      Levels of Lp(a) are influenced by several factors like nutrition, kidney or liver
      function, or acute-phase reaction. But the most important factors are genetically
      determined. About 45% of genetic variation depends on polymorphisms and mutations
      in the promotor region. About 50% are dependent on the size polymorphism of
      Lp(a). The number of Kringle 4 domains varies between 12 and over 40. The number
      of Kringle 4 repeats correlates negatively with the level of Lp(a) in plasma. The
      determination of apo(a) phenotype is able to estimate thromboembolic risk due to
      this risk factor.

PMID- 23546735
TI  - A new genotype of Miscanthus sacchariflorus Geodae-Uksae 1, identified by growth
      characteristics and a specific SCAR marker.
AB  - Miscanthus is referred to as an ideal lignocellulosic bioenergy crop, which can
      be used to generate heat, power, and fuel, as well as to reduce carbon dioxide
      emissions. The new Miscanthus sacchariflorus genotype named Geodae-Uksae 1 was
      recently collected from damp land in southern Korea. This study investigated the
      growth characteristics of Miscanthus genotypes, and developed a specific,
      sensitive, and reproducible sequence characterized amplified region (SCAR) marker
      to distinguish new M. sacchariflorus genotype Geodae-Uksae 1 from other native
      Miscanthus species in Korea. Growth characteristics such as stem length, stem
      diameter, and dry weight of Geodae-Uksae 1 were greater than those of normal M.
      sacchariflorus. The genotypes within Geodae-Uksae 1 were had the highest genetic
      similarity. A putative 1,800-bp polymorphic sequence specific to Geodae-Uksae 1
      was identified with the random amplified polymorphic DNA (RAPD) N8018 primer. The
      sequence-characterized amplified region (SCAR) primers Geodae 1-F and Geodae 1-R
      were designed based on the unique RAPD amplicon. The SCAR primers produced a
      specific 1,799-bp amplicon in authentic Geodae-Uksae 1, whereas no amplification
      was observed in other Miscanthus species. The SCAR marker could contribute to
      identify Geodae-Uksae 1 among native Miscanthus species. The new Miscanthus
      genotype Geodae-Uksae 1 has great potential as an alternative lignocellulosic
      biomass feedstock for bioenergy productions.

PMID- 23546737
TI  - The uneasy (and changing) relationship of health care and religion in our legal
      system.
AB  - This article provides a brief introduction to the interplay between law and
      religion in the health care context. First, I address the extent to which the
      commitments of a faith tradition may be written into laws that bind all citizens,
      including those who do not share those commitments. Second, I discuss the law's
      accommodation of the faith commitments of individual health care providers-hardly
      a static inquiry, as the degree of accommodation is increasingly contested.
      Third, I expand the discussion to include institutional health care providers,
      arguing that the legal system's resistance to accommodating the morally distinct
      identities of institutional providers reflects a short-sighted view of the
      liberty of conscience. Finally, I offer some tentative thoughts about why these
      dynamics become even more complicated in the context of Islamic health care
      providers.

PMID- 23546736
TI  - Not quite dead: why Egyptian doctors refuse the diagnosis of death by
      neurological criteria.
AB  - Drawing on two years of ethnographic fieldwork in Egypt focused on organ
      transplantation, this paper examines the ways in which the "scientific" criteria
      of determining death in terms of brain function are contested by Egyptian
      doctors. Whereas in North American medical practice, the death of the "person" is
      associated with the cessation of brain function, in Egypt, any sign of biological
      life is evidence of the persistence, even if fleeting, of the soul. I argue that
      this difference does not exemplify an irresolvable culture clash but points to an
      unsettling aspect of cadaveric organ procurement that has emerged wherever organ
      transplantation is practiced. Further, I argue that a misdiagnosis of the
      problem, as one about "religious extremism" or a "civilizational clash," has
      obfuscated unresolved concerns about fairness, access, and justice within
      Egyptian medical spheres. This misdiagnosis has led to the suspension of a
      cadaveric procurement program for over 30 years, despite Egypt's pioneering
      efforts in kidney transplantation.

PMID- 23546738
TI  - Low birth weight and health expenditures from birth to late adolescence.
AB  - OBJECTIVES: The aim of this paper is to analyze the impact of low birth weight
      (LBW) and very low birth weight (VLBW) on health care utilization in childhood
      and early adolescence. DATA/METHODS: Using Austrian health insurance
      administrative panel data linked to the Austrian birth register, we estimate the
      effects of LBW and VLBW in comparison to normal birth weight (NBW) on the number
      of days spent in the hospital and on expenditures for medical assistance and
      medical drugs among children and young adults between birth and 21 years of age.
      To account for the time-invariant heterogeneity of mothers, we control for
      sibling fixed effects. RESULTS: We find that, in comparison to their NBW
      counterparts, LBW infants spend more days hospitalized and more is spent on
      medical drugs (particularly on anti-infectives) for them in their first year of
      life. Although the absolute differences in health service utilization between NBW
      and LBW groups diminish over time, LBW newborns still spend more days
      hospitalized, and their medical drug and medical assistance expenses are
      significantly higher in early childhood. During compulsory schooling, we observe
      a shift toward diseases of the nervous system and mental and behavioral disorders
      among children born with LBW. Some of these effects persist until early
      adulthood. CONCLUSIONS: We argue for further counseling efforts for expectant
      mothers on the determinants and risk factors of LBW. Moreover, pre-school
      screenings especially tailored to LBW infants with a particular focus on mental
      health and behavioral disorders can be easily integrated in the existing
      postnatal mother-child care program in Austria to mitigate the consequences of
      negative conditions during pregnancy.

PMID- 23546739
TI  - Education, cognition, health knowledge, and health behavior.
AB  - Using data from NLSY97, we analyze the impact of education on health behavior.
      Controlling for health knowledge does not influence the impact of education on
      health behavior, supporting the productive efficiency hypothesis. Accounting for
      cognitive ability does not significantly alter the relationship between education
      and health behavior. Similarly, the impact of education on health behavior is the
      same between those with and without a learning disability, suggesting that
      cognition is not likely to be a significant factor in explaining the impact of
      education on health behavior. 

PMID- 23546740
TI  - Involvement of volume-activated chloride channels in H2O 2 preconditioning
      against oxidant-induced injury through modulating cell volume regulation
      mechanisms and membrane permeability in PC12 cells.
AB  - The functions of chloride channels in preconditioning-induced cell protection
      remain unclear. In this report, we show that the volume-activated chloride
      channels play a key role in hydrogen peroxide (H2O2) preconditioning-induced cell
      protection in pheochromocytoma PC12 cells. The preconditioning with 100 MUM H2O2
      for 90 min protected the cells from injury induced by long period exposure to 300
      MUM H2O2. The protective effect was attenuated by pretreatment with the chloride
      channel blockers, 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB) and
      tamoxifen. H2O2 preconditioning directly activated a chloride current, which was
      moderately outward-rectified and sensitive to the chloride channel blockers and
      hypertonicity-induced cell shrinkage. H2O2 preconditioning functionally up
      regulated the activities of volume-activated chloride channels and enhanced the
      regulatory volume decrease when exposure to extracellular hypotonic challenges.
      In addition, acute application of H2O2 showed distinctive actions on cell volume
      and membrane permeability in H2O2 preconditioned cells. In H2O2 preconditioned
      cells, acute application of 300 MUM H2O2 first promptly induced a decrease of
      cell volume and enhancement of cell membrane permeability, and then, cell volume
      was maintained at a relatively stable level and the facilitation of membrane
      permeability was reduced. Conversely, in control cells, 300 MUM H2O2 induced a
      slow but persistent apoptotic volume decrease (AVD) and facilitation of membrane
      permeability. H2O2 preconditioning also significantly up-regulated the expression
      of ClC-3 protein, the molecular candidate of the volume-activated chloride
      channel. These results suggest that H2O2 preconditioning can enhance the
      expression and functional activities of volume-activated chloride channels,
      thereby modulate cell volume and cell membrane permeability, which may contribute
      to neuroprotection against oxidant-induced injury.

PMID- 23546743
TI  - Sources and derivation of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are pluripotent cells derived from the inner
      cell mass (ICM) of the developing embryo. hESCs culture as cell lines in vitro
      and possess great potential in such research fields as developmental biology and
      cell-based therapy, as well as such industrial purposes as drug screening and
      toxicology. When ESCs were first derived by Thomson and colleagues, traditional
      methods of immunostaining and culturing, using primary mouse embryonic
      fibroblasts and medium supplemented by serum were used. Considerable efforts have
      since led to improved methods for isolating new lines in defined and reproducible
      conditions. This chapter discusses sources for embryos for ESC isolation,
      commonly used methods for deriving hESC lines, and a number of possible culture
      systems.

PMID- 23546741
TI  - Laforin prevents stress-induced polyglucosan body formation and Lafora disease
      progression in neurons.
AB  - Glycogen, the largest cytosolic macromolecule, is soluble because of intricate
      construction generating perfect hydrophilic-surfaced spheres. Little is known
      about neuronal glycogen function and metabolism, though progress is accruing
      through the neurodegenerative epilepsy Lafora disease (LD) proteins laforin and
      malin. Neurons in LD exhibit Lafora bodies (LBs), large accumulations of
      malconstructed insoluble glycogen (polyglucosans). We demonstrated that the
      laforin-malin complex reduces LBs and protects neuronal cells against endoplasmic
      reticulum stress-induced apoptosis. We now show that stress induces polyglucosan
      formation in normal neurons in culture and in the brain. This is mediated by
      increased glucose-6-phosphate allosterically hyperactivating muscle glycogen
      synthase (GS1) and is followed by activation of the glycogen digesting enzyme
      glycogen phosphorylase. In the absence of laforin, stress-induced polyglucosans
      are undigested and accumulate into massive LBs, and in laforin-deficient mice,
      stress drastically accelerates LB accumulation and LD. The mechanism through
      which laforin-malin mediates polyglucosan degradation remains unclear but
      involves GS1 dephosphorylation by laforin. Our work uncovers the presence of
      rapid polyglucosan metabolism as part of the normal physiology of
      neuroprotection. We propose that deficiency in the degradative phase of this
      metabolism, leading to LB accumulation and resultant seizure predisposition and
      neurodegeneration, underlies LD.

PMID- 23546744
TI  - A new chemical approach to the efficient generation of mouse embryonic stem
      cells.
AB  - Here, we present a highly efficient and reproducible method for the establishment
      of mouse embryonic stem cells (mESCs) from embryonic day 3.5 (E3.5) whole
      blastocysts. This protocol involves the use of small molecules SB431542 and
      PD0325901, which inhibit transforming growth factor-beta (TGF-beta) and
      extracellular signal-regulated kinases (ERK1/2), respectively. This protocol is
      universal in the derivation of mESC lines from NMRI, C57BL/6, BALB/c, DBA/2, and
      FVB/N strains, which have previously been considered refractory or non-permissive
      for ESC establishment. The efficiency of mESC lines generation is 100%,
      regardless of genetic background.

PMID- 23546746
TI  - Generation of human-induced pluripotent stem cells by lentiviral transduction.
AB  - Human somatic cells can be reprogrammed to the pluripotent state to become human
      induced pluripotent stem cells (hiPSC). This reprogramming is achieved by
      activating signaling pathways that are expressed during early development. These
      pathways can be induced by ectopic expression of four transcription factors-Oct4,
      Sox2, Klf4, and c-Myc. Although there are many ways to deliver these
      transcription factors into the somatic cells, this chapter will provide protocols
      that can be used to generate hiPSC from lentiviruses.

PMID- 23546745
TI  - A review of the methods for human iPSC derivation.
AB  - The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs)
      offers an opportunity to generate pluripotent patient-specific cell lines that
      can help model human diseases. These iPSC lines could also be powerful tools for
      drug discovery and the development of cellular transplantation therapies. Many
      methods exist for generating iPSC lines but those best suited for use in studying
      human diseases and developing therapies must be of adequate efficiency to produce
      iPSCs from samples that may be of limited abundance, capable of reprogramming
      cells from both skin fibroblasts and blood, and footprint-free. Several
      reprogramming techniques meet these criteria and can be utilized to derive iPSCs
      in projects with both basic scientific and therapeutic goals. Combining these
      reprogramming methods with small molecule modulators of signaling pathways can
      lead to successful generation of iPSCs from even the most recalcitrant patient
      derived somatic cells.

PMID- 23546747
TI  - Generation of induced pluripotent stem cells with CytoTune, a non-integrating
      Sendai virus.
AB  - One of the major obstacles in generating induced pluripotent stem cells for
      research or downstream applications is the potential modifications of cellular
      genome as a result of using integrating viruses during reprogramming. Another
      major disadvantage of reprogramming cells with integrating vectors is that
      silencing and activation of transgenes are unpredictable, which may affect
      terminal differentiation potential and increase the risk of using iPSC-derived
      cells. Here we describe a protocol for the generation of induced pluripotent stem
      cells using a non-integrating RNA virus, Sendai virus, to efficiently generate
      transgene-free iPSCs starting with different cell types as well as in feeder-free
      conditions.

PMID- 23546742
TI  - The senescence hypothesis of disease progression in Alzheimer disease: an
      integrated matrix of disease pathways for FAD and SAD.
AB  - Alzheimer disease (AD) is a progressive, neurodegenerative disease characterised
      in life by cognitive decline and behavioural symptoms and post-mortem by the
      neuropathological hallmarks including the microtubule-associated protein tau
      reactive tangles and neuritic plaques and amyloid-beta-protein-reactive senile
      plaques. Greater than 95 % of AD cases are sporadic (SAD) with a late onset and
      <5 % of AD cases are familial (FAD) with an early onset. FAD is associated with
      various genetic mutations in the amyloid precursor protein (APP) and the
      presenilins (PS)1 and PS2. As yet, no disease pathway has been fully accepted and
      there are no treatments that prevent, stop or reverse the cognitive decline
      associated with AD. Here, we review and integrate available environmental and
      genetic evidence associated with all forms of AD. We present the senescence
      hypothesis of AD progression, suggesting that factors associated with AD can be
      seen as partial stressors within the matrix of signalling pathways that underlie
      cell survival and function. Senescence pathways are triggered when stressors
      exceed the cells ability to compensate for them. The APP proteolytic system has
      many interactions with pathways involved in programmed senescence and APP
      proteolysis can both respond to and be driven by senescence-associated
      signalling. Disease pathways associated with sporadic disease may be different to
      those involving familial genetic mutations. The interpretation we provide
      strongly points to senescence as an additional underlying causal process in
      dementia progression in both SAD and FAD via multiple disease pathways.

PMID- 23546748
TI  - Generation of human-induced pluripotent stem cells (hiPSCs) using episomal
      vectors on defined Essential 8TM Medium conditions.
AB  - Human-induced pluripotent stem cells (iPSCs) are an important potential source of
      cells for regenerative medicine due to their inherent ability to differentiate
      into all cell types of the three germ layers. Generation of iPSCs with a non
      integrating reprogramming method and in culture conditions that are completely
      absent of animal proteins will be ideal for such regenerative and cell therapy
      applications. Here we describe a method to generate non-integrating iPSCs using
      the Episomal iPSC Reprogramming Vectors.

PMID- 23546749
TI  - Feeder-free substrates for pluripotent stem cell culture.
AB  - A significant barrier to the therapeutic application of pluripotent stem cells
      (PSCs) is the risk associated with the presence of undefined, animal-derived
      elements that are routinely used to culture these cells. Originally, PSCs were
      derived on mouse feeder cells in media containing fetal calf serum. Such
      conditions could expose potential patients to animal pathogens or lead to immune
      rejection. Substantial efforts have been made to remove these components and
      successfully maintain these cells in a completely defined, xeno-free environment.
      In this chapter, we examine substrates consisting of animal-derived proteins,
      purified human proteins, recombinant human proteins, and synthetic polymers and
      their ability to maintain the undifferentiated growth of various pluripotent stem
      cell lines in a variety of supplemented media.

PMID- 23546750
TI  - Methods for culturing human embryonic stem cells on feeders.
AB  - Human embryonic stem cells can be cultured and maintained on fibroblast feeder
      cells of murine or human origin. Thorough protocols are provided for the growth
      and maintenance of human embryonic stem cells on either feeder cell type.

PMID- 23546751
TI  - Methods for culturing human embryonic stem cells in a xeno-free system.
AB  - Defined pluripotent stem cell culture media is a valuable tool for tracking and
      analyzing morphological, cell signaling and gene expression changes in human
      embryonic stem cells. Cultivation of hESC under xeno-free culture settings
      provides researchers with a consistent and reproducible environment to test
      experimental hypotheses and move towards translational and clinical research
      (Richards et al., Nat Biotechnol 20:933-936, 2002; Richards et al., Stem Cells
      21:546-556, 2003). One of the primary concerns of the xenogeneic culture is the
      transfer of foreign pathogens or antigens that induce disease or immune response
      by the patient. These undesirable by-products may come from the use of murine
      derived feeder cells, xenogeneic matrices, or from animal-derived components
      found in the cell culture medium or matrix used to isolate or expand the stem
      cells (Beattie et al., Stem Cells 23:489-495, 2005; Koivisto et al., Reprod
      Biomed Online 9:330-337, 2004). This chapter describes standardized protocols for
      obtaining consistent and reproducible results for culturing PSC under xeno-free,
      feeder-free, or feeder-based systems.

PMID- 23546752
TI  - Directed differentiation of human pluripotent stem cells along the pancreatic
      endocrine lineage.
AB  - Many research groups are engaged in using human pluripotent stem cells (hPSCs) to
      generate surrogate pancreatic beta-cells for transplantation into diabetic
      patients. However, to our knowledge, there is no report on the successful
      generation of glucose-responsive insulin-producing beta-cells from hPSCs in
      vitro. Below, we outline a method that is based on published protocols as well as
      our own experience by which one can differentiate hPSCs along the pancreatic
      lineage to generate insulin-producing beta-cell-like cells. The protocol, which
      spans five distinct stages, is an attempt to recapitulate the derivation of
      pancreatic beta-cells in vitro as they form in the developing embryo. We included
      details on materials and techniques, suggest ways to customize it to your hPSC
      line of choice, added notes on how to monitor and analyze the cells during
      differentiation, and indicate what results can be expected.

PMID- 23546753
TI  - Directed differentiation of pluripotent stem cells to functional hepatocytes.
AB  - Differentiation of human stem cells to hepatocytes is crucial for industrial
      applications as well as to develop new therapeutic strategies for liver disease.
      The protocol described here, using sequentially growth factors known to play a
      role in liver embryonic development, efficiently differentiates human embryonic
      stem cells (hESC) as well as human-induced pluripotent stem cells (hiPSC) to
      hepatocytes by directing them through defined embryonic intermediates, namely,
      mesendoderm/definitive endoderm and hepatoblast and hepatocyte phenotype. After
      28 days, the final differentiated progeny is a mixture of cells, comprising cells
      with characteristics of hepatoblasts and a smaller cell fraction with
      morphological and phenotypical features of mature hepatocytes. An extensive
      functional characterization of the stem cell progeny should be used to confirm
      that differentiated cells display functional characteristics of mature
      hepatocytes including albumin secretion, glycogen storage, and several
      detoxifying functions such as urea production, bilirubin conjugation, glutathione
      S-transferase activity, cytochrome activity and drug transporter activity.

PMID- 23546754
TI  - Highly efficient directed differentiation of human induced pluripotent stem cells
      into cardiomyocytes.
AB  - Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are a novel
      source of cells for patient-specific cardiotoxicity drug testing, drug discovery,
      disease modeling, and regenerative medicine. We describe a versatile and cost
      effective protocol for in vitro cardiac differentiation that is effective for a
      wide variety of hiPSC and human embryonic stem cell (hESC) lines. This highly
      optimized protocol produces contracting human embryoid bodies (hEB) with a near
      total efficiency of 94.7  +/-  2.4% in less than 9 days, and minimizes the
      variability in cardiac differentiation commonly observed between various hiPSC
      and hESC lines. The contracting hEB derived using these methods contain high
      percentages of pure functional cardiomyocytes, highly reproducible
      electrophysiological profiles, and pharmacologic responsiveness to known
      cardioactive drugs.

PMID- 23546755
TI  - Generation of transgene-free iPSC lines from human normal and neoplastic blood
      cells using episomal vectors.
AB  - Human induced pluripotent stem cells (iPSCs) have become an important tool for
      modeling human diseases and are considered a potential source of therapeutic
      cells. Original methods for iPSC generation use fibroblasts as a cell source for
      reprogramming and retroviral vectors as a delivery method of the reprogramming
      factors. However, fibroblasts require extended time for expansion and viral
      delivery of transgenes results in the integration of vector sequences into the
      genome which is a source of potential insertion mutagenesis, residual
      expressions, and reactivation of transgenes during differentiation. Here, we
      provide a detailed protocol for the efficient generation of transgene-free iPSC
      lines from human bone marrow and cord blood cells with a single transfection of
      non-integrating episomal plasmids. This method uses mononuclear bone marrow and
      cord blood cells, and makes it possible to generate transgene-free iPSCs 1-3
      weeks faster than previous methods of reprogramming with fibroblasts.
      Additionally, we show that this approach can be used for efficient reprogramming
      of chronic myeloid leukemia cells.

PMID- 23546756
TI  - Cellular characterization of human pluripotent stem cells.
AB  - Human pluripotent stem cells (PSCs), in particular induced PSCs, are very
      difficult to derive, grow, and bank. They require extensive amounts of resources
      and time to render them useful for basic and applied research. As the derivation
      methods, culture systems and tissues of origin differ, so does the quality of the
      PSCs themselves. Consequently, there are generally accepted molecular and
      cellular markers that serve as benchmarks of pluripotency. PSCs undergo rigorous
      qualification before they can be truly considered a stem cell or completely
      reprogrammed into a stem-like cell as in the case of iPSCs. Morphology is a good
      indicator of PSCs but the further qualification of cellular markers of
      pluripotency and differential potential is necessary. The standard methods
      enclosed in this chapter delineate the techniques necessary to qualify PSCs at
      the cellular level.

PMID- 23546757
TI  - TaqMan(r) OpenArray(r) high-throughput transcriptional analysis of human
      embryonic and induced pluripotent stem cells.
AB  - It is widely accepted that somatic cells can be reprogrammed by a set of
      transcription factors to become embryonic stem cell-like: These reprogrammed
      cells, induced pluripotent stem cells (iPSCs), are nearly identical to embryonic
      stem cells (ESCs), because both have the capacity to self-renew and to form all
      cellular lineages of the body. Transcriptional differences between ESCs, iPSCs,
      and fibroblasts can be analyzed by quantitative PCR (qPCR) using TaqMan((r)) Gene
      Expression assays, a widely used tool for rapid analysis of different cell types.
      In this chapter, we describe the OpenArray((r)) platform which generates qPCR
      data from high-throughput instrumentation. We examined the gene signature
      profiles of ESCs, fibroblasts, and iPSCs with a TaqMan((r)) OpenArray((r)) Human
      Stem Cell Panel containing 631 TaqMan((r)) Gene Expression assays that represent
      pathways involved in self-renewal, pluripotency, lineage patterning,
      transcriptional networks, stem cell differentiation, and development.

PMID- 23546759
TI  - Single cell gene expression analysis of pluripotent stem cells.
AB  - Analyzing gene expression profiles from cells en masse provides an average
      profile for the population which may obscure differences in individual cells.
      Using an optimized workflow for qRT-PCR, gene expression profiles of
      undifferentiated pluripotent stem cells reveal distinct gene expression profiles
      for individual cells, and a large expression level range of almost every gene.
      Importantly, this technique allows for the identification and characterization of
      small subpopulations.

PMID- 23546758
TI  - Epigenome analysis of pluripotent stem cells.
AB  - Mis-regulation of gene expression due to epigenetic abnormalities has been linked
      with complex genetic disorders, psychiatric illness, and cancer. In addition, the
      dynamic epigenetic changes that occur in pluripotent stem cells are believed to
      impact regulatory networks essential for proper lineage development. Chromatin
      immunoprecipitation (ChIP) is a technique used to enrich genomic fragments using
      antibodies against specific chromatin modifications, such as DNA-binding proteins
      or modified histones. Until recently, many ChIP protocols required large numbers
      of cells for each immunoprecipitation. This severely limited analysis of rare
      cell populations or post-mitotic, differentiated cell lines. Here, we describe a
      low cell number ChIP protocol with next generation sequencing and analysis that
      has the potential to uncover novel epigenetic regulatory pathways that were
      previously difficult or impossible to obtain.

PMID- 23546760
TI  - Profiling stem cells using quantitative PCR protein assays.
AB  - Reprogramming human somatic cells to induced pluripotent stem cells is an
      important avenue in biological research. Advances in the profiling of human stem
      cells have identified important pluripotency maintenance factors. The presence
      and relative expression levels of these essential markers are commonly used to
      define the pluripotency status and potential of reprogrammed stem cells. We
      reprogram human dermal fibroblasts with four transcription factors, OCT3/4, SOX2,
      KLF4, and cMYC delivered by viral vectors. We describe a real-time quantitative
      PCR methodology to quantify the levels of key protein factors and examine the
      kinetics during reprogramming as well as comparing protein expression in
      different iPS clones. This report describes three applications of TaqMan((r))
      Protein Assays for reprogramming studies: (1) monitoring of reprogramming
      proteins over the induction time course, (2) characterization of pluripotent
      cells by protein expression profiles, and (3) identification of potential iPSC
      colonies in high-throughput screening protocols. This approach is fast, simple,
      sensitive and generates a pluripotency scorecard for reprogrammed stem cells.

PMID- 23546761
TI  - Labeled stem cells as disease models and in drug discovery.
AB  - Human pluripotent stem cells provide unique possibilities for in vitro studies of
      human cells in basic research, disease modeling as well as in industrial
      applications. By introducing relevant genome engineering technology, and thereby
      creating, for example, reporter cell lines, one will facilitate and improve
      safety pharmacology, toxicity testing, and can help the scientists to better
      understand pathological processes in humans. This review discusses how the merger
      of these two fields, human pluripotent stem cells and genome engineering, form
      extremely powerful tools and how they have been implemented already within the
      scientific community. In sharp contrast to immortalized human cell lines, which
      are both easy to expand and very simple to transfect, the genetically modified
      pluripotent stem cell line can be directed to a specific cell lineage and provide
      the user with highly relevant information. We highlight some of the challenges
      the field had to solve and how new technology advancements has removed the early
      bottlenecks.

PMID- 23546762
TI  - Cloning technologies.
AB  - One major obstacle in realizing the potential behind human embryonic stem cells
      (hESC) is the availability of efficient and reliable engineering methods. Such
      methods require cloning technologies that can be applied to a variety of
      platforms and can serve multiple functions. In the last two decades cloning
      technologies have become more efficient, widening the bottleneck in creating
      engineered hESC lines. Using TOPO((r)) TA cloning kits, genes can be efficiently
      amplified and inserted into target vectors with minimal manipulation and
      purification. For more complex cloning procedures we introduce the Multisite
      Gateway((r)) system. This is a cloning platform based on integrase technology
      that allows for the generation of complex multicistronic gene configurations that
      can transverse a variety of platforms with ease. These technologies allow the end
      user to quickly and efficiently select clones, as well as combine multiple
      genetic elements of interest between platform technologies in a high-throughput
      manner, providing scientists with a toolbox to create tools to dissect stem cell
      biology.

PMID- 23546763
TI  - Stable transfection using episomal vectors to create modified human embryonic
      stem cells.
AB  - Gene delivery into stem cells can be achieved using viral and nonviral methods.
      Nonviral methods are more appealing and the use of episomal vectors that do not
      integrate into the genome enables expression of transgene that are not subject to
      genomic loci effects that could affect expression levels. Here we describe in
      detail transfection and stable pooled clone creation of human embryonic stem
      cells with episomal vectors.

PMID- 23546764
TI  - Site-specific integration in human ESC using Jump-InTM TITM technology.
AB  - Engineering of human embryonic stem cells (hESC) offers a great potential tool
      for the study of human gene function. There are many techniques that can be used
      to engineer human cells, but most are lacking in either specificity or
      efficiency. Jump-InTM TITM technology utilizes two bacteriophage recombinases
      (PhiC31 and R4) to specifically, efficiently, and stably introduce genetic
      elements into the genome of human ESCs. The techniques described here allow the
      user to first deliver a targeting site to a defined locus, and second to deliver
      the genetic elements of interest to that targeting site, allowing for stable,
      single copy integration into the genome. These integrated elements show high
      levels of expression in the pluripotent state, as well as in multiple
      differentiated lineages.

PMID- 23546765
TI  - Small high-density lipoprotein (HDL) subclasses are increased with decreased
      activity of HDL-associated phospholipase A2 in subjects with prediabetes.
AB  - Alterations in high-density lipoprotein (HDL) subclass distribution, as well as
      in the activities of HDL-associated enzymes, have been associated with increased
      cardiovascular disease (CVD) risk. HDL subclass distribution and the activities
      of HDL-associated enzymes remain unknown in prediabetic patients, a condition
      also associated with increased CVD risk. The aim of the present study was to
      assess any differences in HDL subclass distribution (using polyacrylamide gel
      electrophoresis) and in activities of HDL-associated enzymes between prediabetic
      (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105).
      Subjects with prediabetes had significantly increased waist circumference, blood
      pressure and triacylglycerol (TAG) levels compared with subjects with fasting
      glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL
      cholesterol (HDL-C) was significantly increased in prediabetic subjects compared
      with their controls (p < 0.05). The activity of the anti-atherogenic HDL
      associated lipoprotein-associated phospholipase A2 (HDL-LpPLA2) was significantly
      lower in subjects with prediabetes (p < 0.05), whereas the activity of
      paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not
      significantly differ between subjects with or without prediabetes. In a stepwise
      linear regression analysis, the proportion of small HDL3 over HDL-C concentration
      was independently associated with the presence of prediabetes and with total
      cholesterol and TAG concentration (positively), as well as with HDL-C levels
      (negatively). We also observed a trend of increased small dense low-density
      lipoprotein cholesterol levels in prediabetic subjects compared with their
      controls. Subjects with IFG exhibit increased proportion of small HDL3 particles
      combined with decreased activity of the anti-atherogenic HDL-LpPLA2.

PMID- 23546766
TI  - Design and methodology of the Swiss Transplant Cohort Study (STCS): a
      comprehensive prospective nationwide long-term follow-up cohort.
AB  - In Switzerland, organ procurement is well organized at the national-level but
      transplant outcomes have not been systematically monitored so far. Therefore, a
      novel project, the Swiss Transplant Cohort Study (STCS), was established. The
      STCS is a prospective multicentre study, designed as a dynamic cohort, which
      enrolls all solid organ recipients at the national level. The features of the
      STCS are a flexible patient-case system that allows capturing all transplant
      scenarios and collection of patient-specific and allograft-specific data. Beyond
      comprehensive clinical data, specific focus is directed at psychosocial and
      behavioral factors, infectious disease development, and bio-banking. Between May
      2008 and end of 2011, the six Swiss transplant centers recruited 1,677 patients
      involving 1,721 transplantations, and a total of 1,800 organs implanted in 15
      different transplantation scenarios. 10 % of all patients underwent re
      transplantation and 3% had a second transplantation, either in the past or during
      follow-up. 34% of all kidney allografts originated from living donation. Until
      the end of 2011 we observed 4,385 infection episodes in our patient population.
      The STCS showed operative capabilities to collect high-quality data and to
      adequately reflect the complexity of the post-transplantation process. The STCS
      represents a promising novel project for comparative effectiveness research in
      transplantation medicine.

PMID- 23546767
TI  - Intratumoral inflammation is associated with more aggressive prostate cancer.
AB  - PURPOSE: Inflammation may play a role in the development and progression of many
      cancers, including prostate cancer. We sought to test whether histological
      inflammation within prostate cancer was associated with more aggressive disease.
      METHODS: The slides of prostatectomy specimens were reviewed by a board-certified
      pathologist on 287 men from a Veterans Affairs Medical Center treated with
      radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden
      was scored in a blinded manner for the degree of inflammation: absent, mild, or
      marked. We used logistic and Cox proportional hazards regression analysis to
      examine whether categorically coded inflammation score was associated with
      adverse pathology and biochemical progression, respectively. RESULTS: No
      inflammation was found in 49 men (17%), while 153 (53%) and 85 (30%) had mild and
      marked inflammation. During a median follow-up of 77 months, biochemical
      recurrence occurred among 126 (44%) men. On multivariate analysis, more
      inflammation was associated with greater risk of positive margins, capsular
      penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was
      associated with increased PSA recurrence risk when adjusting for preoperative
      features only (HR 2.08, 95% CI 1.02-4.24), but not after adjusting for pathologic
      features. CONCLUSIONS: Inflammation within prostate cancer was associated with
      more advanced disease, although it is unclear whether aggressive disease caused
      increased inflammation or inflammation caused aggressive disease.

PMID- 23546768
TI  - Surgical resection of a giant mediastinal teratoma occupying the entire left
      hemithorax.
AB  - An 11-year-old female was referred to our hospital with a giant mediastinal mass
      occupying the entire left hemithorax. Percutaneous biopsy showed no evidence of
      immature components or malignant cells. Since the tumor compressed the vital
      structures of the mediastinum with total atelectasis of the left lung, we
      performed median sternotomy with left anterior thoracotomy. The tumor was
      punctured, and part of its fluid content was aspirated to achieve reduction in
      the size of the mass, making tumor resection easier. The tumor was totally
      resected without complications. A mediastinal tumor occupying the entire
      hemithorax is uncommon; its surgical strategy is discussed in this manuscript. 

PMID- 23546769
TI  - Changing strategy for aortic stenosis with coronary artery disease by
      transcatheter aortic valve implantation.
AB  - Coronary artery disease (CAD) is combined with aortic stenosis (AS) in 40-50 % of
      patients with typical angina. Recently, transcatheter aortic valve implantation
      (TAVI) has changed the guideline for AS in patients with high comorbidity. At the
      same time more than 60 % of isolated CABG has been performed without
      cardiopulmonary bypass in Japan. CABG is recommended and should be considered in
      patients with primary indication for AVR and luminal stenosis >70 % in major
      coronary arteries and the left internal thoracic artery (LITA) by guidelines. AVR
      is indicated for severe AS undergoing CABG. It is generally accepted to perform
      AVR for moderate AS at the time of CABG by valve guidelines. However,
      prophylactic AVR for moderate AS associated with CABG may increase the early
      operative risk and expose the patients to postoperative long-term valve related
      complications. AVR after previous CABG poses potential risk for mortality and
      morbidity. The presence of patent ITA is a significant risk of its injury and
      difficulty of myocardial protection during aortic cross-clamping. Therefore, at
      present, for severe AS previous CABG with patent ITA should be one of the
      definite indications of TAVI. Rationale of TAVI in patients with severe AS and
      CAD has not been clearly delineated. The safety of TAVI irrespective of the
      extent and anatomy of CAD is still controversial. PCI is not appropriate before
      TAVI in high-risk patients with CAD. In the near future hybrid TAVI will be
      realistic considering least operative mortality and morbidity in high-risk
      patients. 

PMID- 23546770
TI  - Mitral valve replacement and septal myectomy for hypertrophic obstructive
      cardiomyopathy.
AB  - A 76-year-old woman with a diagnosis of hypertrophic obstructive cardiomyopathy
      was referred to our hospital's surgical department. Her echocardiogram revealed
      diffuse left ventricular hypertrophy, moderate mitral valve regurgitation with
      systolic anterior motion of the mitral valve, and left ventricular obstruction
      with a peak outflow gradient of 108 mm Hg. We performed a transaortic rectangular
      septal myectomy with an incision at a width, depth, and length of 1 cm, 1 cm, and
      3 cm, respectively. However, the transesophageal echocardiogram revealed residual
      left ventricular obstruction and systolic anterior motion, and we subsequently
      replaced the mitral valve with a mechanical valve. The patient's postoperative
      course was uneventful, and the peak outflow gradient decreased to 15 mm Hg.
      Although transaortic septal myectomy is the most common surgery currently used
      for hypertrophic obstructive cardiomyopathy, mitral valve replacement should
      remain an option in patients with diffuse left ventricular hypertrophy who fail
      to improve after myectomy alone. 

PMID- 23546771
TI  - Introduction to "coping with environmental risk and uncertainty: individual and
      cultural responses".
AB  - The papers in this special issue of Human Nature collectively consider societal
      and individual responses to a wide variety of environmental and social risks. The
      first paper considers societal level effects of pathogen risk on collectivism and
      conformity, avoidance of outsiders, and in-group loyalty in a worldwide cross
      cultural sample. The second deals with societal-level effects of resource
      unpredictability on the nature and conduct of warfare in eastern Africa. The
      third deals with effects of volcanic eruptions and earthquakes and mediating
      factors on individual perceptions of risk in Mexico and Ecuador. The final paper
      deals with effects of various types of father absence on women's reproductive
      life histories in Bangladesh.

PMID- 23546772
TI  - The efficacy and safety of sertaconazole cream (2 %) in diaper dermatitis
      candidiasis.
AB  - AIM: Diaper dermatitis (DD) is an inflammatory irritating condition that is
      common in infants. Most cases are associated with the yeast colonization of
      Candida or diaper dermatitis candidiasis (DDC), and therefore, the signs and
      symptoms improve with antimycotic treatment. Sertaconazole is a broad-spectrum
      third-generation imidazole derivative that is effective and safe for the
      treatment for superficial mycoses, such as tineas, candidiasis, and pityriasis
      versicolor. Our goal was to assess the efficacy and safety of sertaconazole cream
      (2 %) in DDC. MATERIALS AND METHODS: Twenty-seven patients with clinical and
      mycological diagnosis of DDC were enrolled and treated with 2 daily applications
      for 14 days and were followed-up for 2 further weeks. RESULTS: Three etiologic
      agents were isolated: Candida albicans in 88.8 %, Candida parapsilosis in 7.3 %,
      and Candida glabrata in 3.2 %. There was an average symptom reduction from 7.1 to
      3.2 in the middle of treatment and to 1.2 and 0.4 units at the end of treatment
      and follow-up, respectively. The treatment evaluation at the end of the follow-up
      period showed a total clinical and mycological cure in 88.8 %, improvement in 3.7
      %, and failure in 7.4 %. There was side effect (3.7 %) of skin irritation, but
      the drug was not discontinued. CONCLUSIONS: Based on its safety and
      effectiveness, sertaconazole cream may be considered a new alternative for DDC
      treatment.

PMID- 23546773
TI  - Genotyping reveals no link between Candida albicans genotype and vaginitis
      severity in Turkish women.
AB  - Recent studies have clearly defined the vaginopathic Candida albicans strains
      that cause severe vulvovaginal candidiasis (VVC). Therefore, genotyping C.
      albicans isolates may predict the success of and assist in choosing the
      appropriate antifungal therapy. The purpose of this study was to compare the
      genotypes of C. albicans isolates causing VVC with those found in asymptomatic
      healthy pregnant and non-pregnant women in Adana, Turkey, as well as the
      antifungal susceptibility profiles of these isolates. A total of 216 independent
      C. albicans isolates were genotyped by allelic combination based on the
      microsatellite marker analysis of one such microsatellite, present in the
      promoter region of the elongation factor 3-encoding gene (CEF3) of C. albicans.
      The susceptibility testing profiles of all of the isolates against five
      antifungals and boric acid were obtained retrospectively from our laboratory
      records. We identified 20 genotypes on the basis of different allelic
      combinations at the CEF3 locus with a discriminatory power of 0.85. Genotypes 136
      144 and 126-135 were present in 50 % of the isolates. No differences existed in
      the genotypic profiles of fungal isolates between pregnant and non-pregnant
      women. Remarkably, we did not find a single vaginopathic genotype. All of the
      isolates were susceptible to amphotericin B and 5-fluorocytosine, and the
      fluconazole and ketoconazole resistance rates were 0.9 and 3.7 %, respectively.
      Therefore, we did not find any correlation between genotype, severity of VVC, and
      antifungal resistance (P > 0.05). Even so, additional molecular data may provide
      new insights into the management of VVC.

PMID- 23546774
TI  - Computerized determination scheme for histological classification of breast mass
      using objective features corresponding to clinicians' subjective impressions on
      ultrasonographic images.
AB  - It is often difficult for clinicians to decide correctly on either biopsy or
      follow-up for breast lesions with masses on ultrasonographic images. The purpose
      of this study was to develop a computerized determination scheme for histological
      classification of breast mass by using objective features corresponding to
      clinicians' subjective impressions for image features on ultrasonographic images.
      Our database consisted of 363 breast ultrasonographic images obtained from 363
      patients. It included 150 malignant (103 invasive and 47 noninvasive carcinomas)
      and 213 benign masses (87 cysts and 126 fibroadenomas). We divided our database
      into 65 images (28 malignant and 37 benign masses) for training set and 298
      images (122 malignant and 176 benign masses) for test set. An observer study was
      first conducted to obtain clinicians' subjective impression for nine image
      features on mass. In the proposed method, location and area of the mass were
      determined by an experienced clinician. We defined some feature extraction
      methods for each of nine image features. For each image feature, we selected the
      feature extraction method with the highest correlation coefficient between the
      objective features and the average clinicians' subjective impressions. We
      employed multiple discriminant analysis with the nine objective features for
      determining histological classification of mass. The classification accuracies of
      the proposed method were 88.4 % (76/86) for invasive carcinomas, 80.6 % (29/36)
      for noninvasive carcinomas, 86.0 % (92/107) for fibroadenomas, and 84.1 % (58/69)
      for cysts, respectively. The proposed method would be useful in the differential
      diagnosis of breast masses on ultrasonographic images as diagnosis aid.

PMID- 23546776
TI  - Time-lapse microscopy approaches to track cell cycle and lineage progression at
      the single-cell level.
AB  - Time-lapse microscopy can be described as the repeated collection of an image (in
      n-dimensions; x, y, z, lambda) or field of view from a microscope at discrete
      time intervals. The duration of the time interval defines the temporal
      resolution, which in turn characterizes the type of event detected. This unit
      describes the implementation of time-lapse microscopy to link initial cell cycle
      position during acute exposures to anti-cancer agents with anti-proliferative
      consequences for individual cells. The approach incorporates fundamental concepts
      arising from the ability to capture simple video sequences of cells from which it
      is possible to extract kinetic descriptors that reflect the interplay of mitosis
      and cell death in the growth of an unsynchronized tumor population. Utilizing a
      multi-well format enables the user to screen different drug derivatives, multiple
      dose ranges, or cell cultures with unique genetic backgrounds. The objective of
      this unit is to present the basic methodology for capturing time-lapse sequences
      and touch upon subsequent mining of the data for deriving event curves and
      possible cell lineage maps.

PMID- 23546775
TI  - A novel knowledge representation framework for the statistical validation of
      quantitative imaging biomarkers.
AB  - Quantitative imaging biomarkers are of particular interest in drug development
      for their potential to accelerate the drug development pipeline. The lack of
      consensus methods and carefully characterized performance hampers the widespread
      availability of these quantitative measures. A framework to support collaborative
      work on quantitative imaging biomarkers would entail advanced statistical
      techniques, the development of controlled vocabularies, and a service-oriented
      architecture for processing large image archives. Until now, this framework has
      not been developed. With the availability of tools for automatic ontology-based
      annotation of datasets, coupled with image archives, and a means for batch
      selection and processing of image and clinical data, imaging will go through a
      similar increase in capability analogous to what advanced genetic profiling
      techniques have brought to molecular biology. We report on our current progress
      on developing an informatics infrastructure to store, query, and retrieve imaging
      biomarker data across a wide range of resources in a semantically meaningful way
      that facilitates the collaborative development and validation of potential
      imaging biomarkers by many stakeholders. Specifically, we describe the semantic
      components of our system, QI-Bench, that are used to specify and support
      experimental activities for statistical validation in quantitative imaging. 

PMID- 23546777
TI  - Flow cytometric analysis of cell division by dilution of CFSE and related dyes.
AB  - The technique described in this unit uses the intracellular fluorescent label
      carboxyfluorescein diacetate succinimidyl ester (CFSE) to track proliferating
      cells. Covalently bound CFSE is divided equally between daughter cells, allowing
      discrimination of successive rounds of cell division. The technique is applicable
      to in vitro cell division, as well as to in vivo division of adoptively
      transferred cells and can resolve eight or more successive generations. CFSE is
      long lived, permitting analysis for several months after cell transfer, and has
      the same spectral characteristics as fluorescein, so monoclonal antibodies
      conjugated to phycoerythrin or other compatible fluorochromes may be used to
      immunophenotype the dividing cells. In addition, information is given on a second
      generation dye, Cell Trace Violet (CTV), excited by 405-nm blue laser light. CTV
      is chemically related to CFSE, but allows the 488-nm line of the Argon laser to
      be used for other probes.

PMID- 23546778
TI  - Assessment of cell viability.
AB  - Cell viability may be judged by morphological changes or by changes in membrane
      permeability and/or physiological state inferred from the exclusion of certain
      dyes or the uptake and retention of others. This unit presents methods based on
      dye exclusion, esterase activity, and mitochondrial membrane potential, as well
      as protocols for determining the pre-fixation viability of fixed cells either
      before or after fixation with amine-reactive dyes suitable for a range of
      excitation wavelengths. Membrane-impermeable dead cell and live cell dyes as well
      as dye-exclusion procedures for microscopy are also included.

PMID- 23546779
TI  - Flow cytometry of the side population (SP).
AB  - The side population (SP) has become an important hallmark for the definition of
      the stem-cell compartment, especially for the detection of stem cells and for
      their physical isolation by fluorescence-activated cell sorting (FACS). SP cells
      are CD34(-) and were discovered using ultraviolet excitation based on the efflux
      of Hoechst 33342 (Ho342). Although the method works as originally described, the
      protocol is difficult for most investigators to perform: first, because the
      ability to discriminate SP cells is based on the differential retention of Ho342
      during a functional assay; second, because of the difficulties in setting the
      right experimental and acquisition conditions; and third, because analysis of the
      acquired data requires extensive expertise in flow cytometry to accurately detect
      the SP events. More recently, a new assay based on the efflux of Vybrant DyeCycle
      Violet stain (DCV) has been documented to discriminate SP cells. This unit
      contains many helpful pointers to aid the user in obtaining the best possible
      results with these assays.

PMID- 23546780
TI  - Microsatellites: evolution and contribution.
AB  - Microsatellites are codominant molecular genetic markers, which are universally
      dispersed within genomes. These markers are highly popular because of their high
      level of polymorphism, relatively small size, and rapid detection protocols. They
      are widely used in a variety of fundamental and applied fields of biological
      sciences for plants and animal studies. Microsatellites are also extensively used
      in the field of agriculture, where they are used in characterizing genetic
      materials, plant selection, constructing dense linkage maps, mapping economically
      important quantitative traits, identifying genes responsible for these traits. In
      addition microsatellites are used for marker-assisted selection in breeding
      programs, thus speeding up the process. In this chapter, genomic distribution,
      evolution, and practical applications of microsatellites are considered, with
      special emphasis on plant breeding and agriculture. Moreover, novel advances in
      microsatellite technologies are also discussed.

PMID- 23546781
TI  - Screening of genomic libraries.
AB  - Microsatellites, or simple sequence repeats (SSRs), have proven to be an
      important molecular marker in plant genetics and breeding research. The main
      strategies to obtain these markers can be through genomic DNA and from expressed
      sequence tags (ESTs) from mRNA/cDNA libraries. Genetic studies using
      microsatellite markers have increased rapidly because they can be highly
      polymorphic, codominant markers and they show heterozygous conserved sequences.
      Here, we describe a methodology to obtain microsatellite using the enrichment
      library of DNA genomic sequences. This method is highly efficient to development
      microsatellite markers especially in plants that do not have available ESTs or
      genome databases. This methodology has been used to enrich SSR marker libraries
      in Citrus spp., an important tool to genotype germplasm, to select zygotic
      hybrids, and to saturate genetic maps in breeding programs.

PMID- 23546782
TI  - PCR-based isolation of microsatellite arrays (PIMA).
AB  - Microsatellite is one of the most high-speed developing genetic markers for its
      wide application in molecular biology researches. It is proved to be a powerful
      marker-assisted tool in genetic relationship identification, the inheritance
      breeding, the population genetics, the physical map construction, the management
      and security of germplasm. These short tandem repeats loci are distributed
      throughout the eukaryotic genome. They represent not only highly conservative
      trait but also significant differentiation properties between individuals, making
      it advantageous over other molecular markers. Traditionally, hard labor is
      required for isolating these loci and the flanking sequences, including small
      fragment DNA library construction, DNA cloning, radioactive hybridization,
      sequencing, and microsatellite test. PIMA is a relatively simple microsatellite
      isolation technique which avoids not only library construction but also
      radioactivity manipulation. This approach builds on random amplified polymorphic
      DNA (RAPD) process but investigates microsatellite arrays by repeat-specific PCR
      rather than radioactive hybridization. PIMA screening microsatellites use one
      repeat-specific and two vector primers to run PCR. A number of useful vectors are
      widely circulated and the repeat-specific primer is easy to obtain. The
      advantages of obtaining both flank sequences simultaneously, no need of specific
      sequencing primers, the ease of operation, and well amplification of bacterial
      colonies persuade us of its high value. It prevails other tools because of its
      traits of cheaper, high-efficient, and relatively lower requirement of
      specialized equipment tool. Since no protocol is universal and perfect for every
      species, it is recommended that modification should be made according to the
      objective of the experiments. Existing examples serve as good sources of future
      works.

PMID- 23546783
TI  - Fast isolation by AFLP of sequences containing repeats.
AB  - Fast isolation by AFLP of sequences containing repeats (FIASCO) is a rapid and
      simple method for separating microsatellite-containing DNA fragments from genomic
      DNA de novo. The method takes the advantage of the amplified fragment length
      polymorphism (AFLP) technique that relies on effective digestion-ligation
      reaction. The repeat-containing fragments are selectively hybridized to
      biotinylated probes and harvested by streptavidin-coated magnetic beads. The
      enriched microsatellite-containing fragments can be cloned and sequenced to yield
      a variety of microsatellite loci for applications in many different fields in
      molecular genetics.

PMID- 23546784
TI  - Microsatellite DNA capture from enriched libraries.
AB  - Microsatellites are DNA sequences of tandem repeats of one to six nucleotides,
      which are highly polymorphic, and thus the molecular markers of choice in many
      kinship, population genetic, and conservation studies. There have been
      significant technical improvements since the early methods for microsatellite
      isolation were developed, and today the most common procedures take advantage of
      the hybrid capture methods of enriched-targeted microsatellite DNA. Furthermore,
      recent advents in sequencing technologies (i.e., next-generation sequencing, NGS)
      have fostered the mining of microsatellite markers in non-model organisms,
      affording a cost-effective way of obtaining a large amount of sequence data
      potentially useful for loci characterization. The rapid improvements of NGS
      platforms together with the increase in available microsatellite information open
      new avenues to the understanding of the evolutionary forces that shape genetic
      structuring in wild populations. Here, we provide detailed methodological
      procedures for microsatellite isolation based on the screening of GT
      microsatellite-enriched libraries, either by cloning and Sanger sequencing of
      positive clones or by direct NGS. Guides for designing new species-specific
      primers and basic genotyping are also given.

PMID- 23546785
TI  - Next-generation sequencing for high-throughput molecular ecology: a step-by-step
      protocol for targeted multilocus genotyping by pyrosequencing.
AB  - Next-generation sequencing technology can now provide population biologists and
      phylogeographers with information at the genomic scale; however, many pertinent
      questions in population genetics and phylogeography can be answered effectively
      with modest levels of genomic information. For the past two decades, most
      population-level studies have lacked nuclear DNA (nDNA) sequence data due to the
      complications and cost of amplifying and sequencing diploid loci. However,
      pyrosequencing of emulsion PCR reactions, amplifying from only one molecule at a
      time, can generate megabases of clonally amplified loci at high coverage, thereby
      greatly simplifying allelic sequence determination. Here, we present a step-by
      step methodology for utilizing the 454 GS FLX Titanium pyrosequencing platform to
      simultaneously sequence 16 populations (at 20 individuals per population) at 10
      different nDNA loci (3,200 loci in total) in one plate of sequencing for less
      than the cost of traditional Sanger sequencing.

PMID- 23546786
TI  - Optimizing selection of microsatellite loci from 454 pyrosequencing via post
      sequencing bioinformatic analyses.
AB  - The comparatively low cost of massive parallel sequencing technology, also known
      as next-generation sequencing (NGS), has transformed the isolation of
      microsatellite loci. The most common NGS approach consists of obtaining large
      amounts of sequence data from genomic DNA or enriched microsatellite libraries,
      which is then mined for the discovery of microsatellite repeats using
      bioinformatics analyses. Here, we describe a bioinformatics approach to isolate
      microsatellite loci, starting from the raw sequence data through a subset of
      microsatellite primer pairs. The primary difference to previously published
      approaches includes analyses to select the most accurate sequence data and to
      eliminate repetitive elements prior to the design of primers. These analyses aim
      to minimize the testing of primer pairs by identifying the most promising
      microsatellite loci.

PMID- 23546787
TI  - Identification of DNA-microsatellite markers for the characterization of somatic
      embryos in Quercus suber.
AB  - Nuclear DNA-microsatellite markers led the possibility to characterize
      individually both Quercus suber trees and somatic embryos. The genotype inferred
      by SSR markers opens the possibility to obtain a fingerprint for clonal lines
      identification. Furthermore, allow to infer the origin of somatic embryos from
      haploid cells (microspores) or from diploid tissues. Using few SSR markers from
      other Quercus species and an automatic system based in fluorescence, it is
      possible to obtain a high discrimination power between genotypes. This method is
      sufficient to assign tissues to an individual tree with high statistical
      certainty. Nevertheless, it is necessary to take care to select the adequate DNA
      extraction method to avoid PCR inhibitors present in diverse Q. suber tissues.

PMID- 23546788
TI  - Simple sequence repeats amplification.
AB  - The technique of SSR amplification is a prerequisite to generate the molecular
      profiles of various alleles of an individual or genotype. Amplification is the
      multifold duplication and accumulation of a targeted region which is achieved by
      polymerase chain reaction. It needs ingredients such as buffer, MgCl2, dNTPs,
      primers, and DNA polymerase enzyme. The utilization of these essential PCR
      components in optimal concentrations determines the success of amplification.
      Thus SSRs, as primers, play an important role in enhancing the amplification and
      thereby generating the genotype profile. With the advent of technology,
      fluorophore-labeled primers along with automated capillary electrophoresis system
      have enhanced the efficiency of detection.

PMID- 23546789
TI  - Microsatellite amplification in plants: optimization procedure of major PCR
      components.
AB  - Microsatellites (SSRs) are the most informative and popular class of molecular
      markers used for diverse purposes, particularly in plants: genetic diversity
      study, marker assisted selection, breeding, mapping, phylogenetics and
      phylogeography, systematics, etc. They have become a routine technique
      practically in each laboratory for studying molecular plant genetics. Despite
      their wide utilization, however, setup and optimization of various conditions
      involved in PCR amplification is a prerequisite for reliable inference of
      results. In this chapter, we describe optimization of SSR-PCR conditions and give
      ranges of concentrations for different parameters. The protocol provided here is
      inspired from bench work on the use of microsatellite to study diversity of Vitis
      vinifera germplasm.

PMID- 23546790
TI  - Development of a multiplex PCR assay for characterization of embryonic stem
      cells.
AB  - Several molecular methods like real-time PCR (Q-PCR), expression sequence tag
      (EST) scan, microarray and microRNA analysis, and massively parallel signature
      sequencing (MPSS) have proved to be increasingly sensitive and efficient for
      monitoring human embryonic stem cell (hESC) differentiation. However, most of
      these high-throughput tests have a limited use due to high cost, extended
      turnaround time, and the involvement of highly specialized technical expertise.
      Hence, there is a need of rapid, cost-effective, robust, yet sensitive method for
      routine screening of hESCs. A critical requirement in hESC cultures is to
      maintain a uniform undifferentiated state and to determine their differentiation
      capacity by showing the expression of germ-layer-specific gene markers. To
      determine the modulation of gene expression in hESCs during propagation,
      expansion, and differentiation via embryoid body (EB) formation, we developed a
      simple, rapid, inexpensive, and definitive multimarker, semiquantitative
      multiplex RT-PCR (mxPCR) platform technology. Among the 15 gene primers tested, 4
      were pluripotent markers comprising of set 1; and 3 lineage-specific markers from
      each ecto-, meso-, and endoderm layers were combined as sets 2, 3, and 4,
      respectively. In summary, this study was performed to characterize hESCs on a
      molecular level and to determine the quality and degree of variability among hESC
      and their early progenies (EB). This single-reaction mxPCR assay was flexible
      and, by selecting appropriate reporter genes, can be designed for
      characterization of different hESC lines during routine maintenance and directed
      differentiation.

PMID- 23546791
TI  - Agarose gel electrophoresis and polyacrylamide gel electrophoresis for
      visualization of simple sequence repeats.
AB  - In the modern age of genetic research there is a constant search for ways to
      improve the efficiency of plant selection. The most recent technology that can
      result in a highly efficient means of selection and still be done at a low cost
      is through plant selection directed by simple sequence repeats (SSRs or
      microsatellites). The molecular markers are used to select for certain desirable
      plant traits without relying on ambiguous phenotypic data. The best way to detect
      these is the use of gel electrophoresis. Gel electrophoresis is a common
      technique in laboratory settings which is used to separate deoxyribonucleic acid
      (DNA) and ribonucleic acid (RNA) by size. Loading DNA and RNA onto gels allows
      for visualization of the size of fragments through the separation of DNA and RNA
      fragments. This is achieved through the use of the charge in the particles. As
      the fragments separate, they form into distinct bands at set sizes. We describe
      the ability to visualize SSRs on slab gels of agarose and polyacrylamide gel
      electrophoresis.

PMID- 23546792
TI  - Microsatellite fragment analysis using the ABI PRISM (r) 377 DNA sequencer.
AB  - The ABI PRISM ((r)) 377 DNA Sequencer is used for a variety of microsatellite
      based research. The platform provides researchers with a cost-effective means for
      high-throughput genotyping, which can be further optimized by multiplexing
      microsatellite loci or by using a tail-labeling approach to screen large sets of
      markers. The goals of this chapter are to present a protocol for performing
      microsatellite-based analyses on the ABI 377 and to provide researchers with
      information on how to troubleshoot common issues associated with running the ABI
      377 sequencers.

PMID- 23546793
TI  - Robust and inexpensive SSR markers analyses using LI-COR DNA analyzer.
AB  - Plant genotyping is performed for different purposes which dictate to a large
      extent the type of molecular makers and platform to be used. The level of
      throughput, the technical capacity of the genotyping facility, and the
      availability of reagents are also part of the decision towards a particular
      genotyping system. SSR markers are quite popular markers because they are easily
      implementable in standard laboratories, can be used on manual gel
      electrophoresis, require inexpensive reagents, are mostly randomly distributed in
      the genome, can be located within genes, have a good discriminatory power, and
      are codominant with Mendelian inheritance. These features have made SSR the
      marker of choice for low-resolution genetic mapping and genetic diversity studies
      including genetic identity verification. The LI-COR platform offers both
      qualitative and quantitative improvements over the conventional assays based on
      agarose and polyacrylamide (PAGE) gels with DNA stained with ethidium bromide and
      silver or radiolabeled. A fast run coupled with an automated detection system
      using fluorophores makes possible to achieve routinely in our genotyping facility
      five runs per day using the same gel up to four times which results in 48
      genotypes genotyped with ten SSR markers (two per gel electrophoresis using low
      cost M13-tailed primers). This gel-base, low cost per sample and equipment, and
      medium throughput makes the LI-COR platform -particularly useful for laboratories
      with intermediate skills and expectations in molecular genetics.

PMID- 23546794
TI  - The use of the MegaBACE for sequencing and genotype analysis.
AB  - Despite the advent of next generation sequencing techniques, which provide access
      to an enormous amount of genomic information in a relatively short time, the
      conventional Sanger sequencing and microsatellite genotyping analyses present a
      straightforward method to answer clearly defined questions in population
      genetics, phylogeography, or forensics. The MegaBACE is a platform that provides
      both applications with equally reliable performance. In this overview, protocols
      for the classical techniques of Sanger sequencing and microsatellite genotyping
      are described. This chapter aims to supply the user of the MegaBACE with
      methodological tools and some "insider" knowledge of this highly sensitive
      apparatus.

PMID- 23546795
TI  - Analyzing microsatellites using the QIAxcel system.
AB  - Microsatellites are ubiquitous throughout eukaryotic genomes and are useful in
      analyzing populations and genetic diversity. The QIAxcel system, an automated
      capillary electrophoresis device, allows the user to determine the size of
      microsatellite fragments, to discern allelic polymorphisms among individuals, and
      to differentiate homozygous and heterozygous individuals. This system provides
      comparable base pair resolution to more expensive systems at a relatively
      affordable cost.

PMID- 23546796
TI  - Microsatellite analysis of malaria parasites.
AB  - Microsatellites have been increasingly used to investigate the population
      structure of malaria parasites, to map genetic loci contributing to phenotypes
      such as drug resistance and virulence in laboratory crosses and genome-wide
      association studies and to distinguish between treatment failures and new
      infections in clinical trials. Here, we provide optimized protocols for
      genotyping highly polymorphic microsatellites sampled from across the genomes of
      the human malaria parasites Plasmodium falciparum and P. vivax that have been
      extensively used in research laboratories worldwide.

PMID- 23546797
TI  - Informativeness of microsatellite markers.
AB  - Simple sequence repeats (SSR) are extensively used as genetic markers for studies
      of diversity, genetic mapping, and cultivar discrimination. The informativeness
      of a given SSR locus or a loci group depends on the number of alleles, their
      frequency distribution, as well as the kind of application. Here I describe
      several methods for calculating marker informativeness, all of them suitable for
      SSR polymorphisms, proposed by several authors and synthesized in an Information
      Theory framework. Additionally, free access software resources are described as
      well as their application through worked examples.

PMID- 23546798
TI  - Microsatellite data analysis for population genetics.
AB  - Theories and analytical tools of population genetics have been widely applied for
      addressing various questions in the fields of ecological genetics, conservation
      biology, and any context where the role of dispersal or gene flow is important.
      Underlying much of population genetics is the analysis of variation at
      selectively neutral marker loci, and microsatellites continue to be a popular
      choice of marker. In recent decades, software programs to estimate population
      genetics parameters have been developed at an increasing pace as computational
      science and theoretical knowledge advance. Numerous population genetics software
      programs are presently available to analyze microsatellite genotype data, but
      only a handful are commonly employed for calculating parameters such as genetic
      variation, genetic structure, patterns of spatial and temporal gene flow,
      population demography, individual population assignment, and genetic
      relationships within and between populations. In this chapter, we introduce
      statistical analyses and relevant population genetic software programs that are
      commonly employed in the field of population genetics and molecular ecology.

PMID- 23546799
TI  - Molecular mapping and breeding with microsatellite markers.
AB  - In genetics databases for crop plant species across the world, there are
      thousands of mapped loci that underlie quantitative traits, oligogenic traits,
      and simple traits recognized by association mapping in populations. The number of
      loci will increase as new phenotypes are measured in more diverse genotypes and
      genetic maps based on saturating numbers of markers are developed. A period of
      locus reevaluation will decrease the number of important loci as those underlying
      mega-environmental effects are recognized. A second wave of reevaluation of loci
      will follow from developmental series analysis, especially for harvest traits
      like seed yield and composition. Breeding methods to properly use the accurate
      maps of QTL are being developed. New methods to map, fine map, and isolate the
      genes underlying the loci will be critical to future advances in crop
      biotechnology. Microsatellite markers are the most useful tool for breeders. They
      are codominant, abundant in all genomes, highly polymorphic so useful in many
      populations, and both economical and technically easy to use. The selective
      genotyping approaches, including genotype ranking (indexing) based on partial
      phenotype data combined with favorable allele data and bulked segregation event
      (segregant) analysis (BSA), will be increasingly important uses for
      microsatellites. Examples of the methods for developing and using microsatellites
      derived from genomic sequences are presented for monogenic, oligogenic, and
      polygenic traits. Examples of successful mapping, fine mapping, and gene
      isolation are given. When combined with high-throughput methods for genotyping
      and a genome sequence, the use of association mapping with microsatellite markers
      will provide critical advances in the analysis of crop traits.

PMID- 23546800
TI  - Scoring microsatellite loci.
AB  - Microsatellites have been utilized for decades for genotyping individuals in
      various types of research. Automated scoring of microsatellite loci has allowed
      for rapid interpretation of large datasets. Although the use of software produces
      an automated process to score or genotype samples, several sources of error have
      to be taken into account to produce accurate genotypes. A variety of problems
      (from extracting DNA to entering a genotype into a database) which can arise
      throughout this process might result in erroneous genotype assignment to one or
      more samples, potentially confounding the conclusions of your study. Correctly
      assigning a genotype to a sample requires knowledge of the chemistry you use to
      generate the data as well as the software you use to analyze these results. In
      this chapter we describe the critical and more common points that researchers
      experience when scoring microsatellite loci. More importantly we provide insight
      from an experienced perspective for these challenges.

PMID- 23546801
TI  - Arterial vascular cell line expressing SSAO: a new tool to study the
      pathophysiology of vascular amine oxidases.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) widely exists in nature, mainly
      expressed at significant levels in vasculature. It plays a detrimental role in
      vascular diseases, particularly atherosclerosis, which occurs mainly in arteries.
      Herein we for the first time present SSAO expression in arterial lineage of
      vascular cell line, i.e., human umbilical arterial endothelial cell (HUAEC).
      Firstly, two commercially available gene transfection reagents were compared to
      determine high transfection efficiency and then the expression behavior of
      HUAEC:SSAO was characterized. Furthermore, our model was also been compared with
      commonly used human embryonic kidney (HEK) cell transfected with the same vector.
      For enzymatic assay, an in-house developed highly sensitive high performance
      liquid chromatography electron spray ionization mass spectrometry method was
      applied. Results indicated that the maximal transfection efficiency in HUAEC was
      detected by JetPEITM and transfected protein was expressed at membrane and
      cytosol of different clones. No significant variations were observed in HUAEC
      between cell passages 1 and 7, although HEK cell displayed twofold higher SSAO
      expression level than HUAEC. The transfected SSAO was shown to be released into
      the cell-culture medium. Both cellular and released types of SSAO exhibited
      monomer and dimer structural forms. The cytotoxicity determination exhibited
      large number of viable cells after transfection with JetPEITM. Differential
      expression characterization of this new cell line demonstrates the correct
      behavior of SSAO in arterial endothelial cells and also provides a real
      physiological environment to elucidate the unclear role of this enzyme. In
      addition, our cellular model could partly solve the problems raised by the loss
      of enzyme expression found in cultured endothelial cells. This model could also
      be a useful tool for proteomic base study, screening of interacting protein and
      analysis of compounds that could modify its activity for therapeutic purposes.

PMID- 23546802
TI  - Quantum-chemical approach to determining the high potency of clorgyline as an
      irreversible acetylenic monoamine oxidase inhibitor.
AB  - Density functional theory calculations were employed to investigate the nature of
      chemical bond formation between the flavin co-factor of the enzyme monoamine
      oxidase (MAO) and its irreversible acetylenic inhibitor clorgyline in its
      terminally deprotonated anionic form. Since MAOs regulate the level of
      neurotransmitters in living cells, this reaction is pharmacologically relevant
      for treating depression and other mood disorders. The results revealed that this
      pathway is associated with the activation free energy of DeltaG act (#) = 17.4
      kcal mol(-1), which, together with our previous results, suggests that clorgyline
      is intrinsically a more effective MAO inhibitor than antiparkinsonian drugs
      rasagiline and selegiline considering the preferred MAO isoforms in each case,
      thus displaying a trend in agreement with experimental data. The reaction is
      facilitated by the pronounced electrophilic character of the flavin moiety, due
      to its ability to efficiently accommodate excess negative charge from the
      approaching anionic inhibitor through resonance effect. The investigated
      mechanism was additionally validated by the inspection of the geometry of the
      flavin moiety in the formed adduct, which exhibit distortion from planarity
      consistent with experimental observations. These results offer valuable insight
      for mechanistic studies on other flavoenzymes and for the design of new
      antidepressants and antiparkinsonian drugs.

PMID- 23546803
TI  - Ancient schwannoma involving the median nerve: a case report and review of the
      literature.
AB  - Ancient schwannomas are benign long standing schwannomas of the neural sheaths.
      Histological findings are these seen as in conventional schwannomas, but ancient
      schwannomas additionally demonstrate cystic hemorrhagic changes and degenerative
      nuclei with pleomorphism and hyperchromasia. Due to the nuclear atypia, and
      cystic degeneration, ancient schwannomas might be confused with malignant tumors
      on histology and imaging, leading to a radical surgical approach. The median
      nerve is rarely affected. We present a rare case of an ancient schwannoma
      involving the median nerve at the mid humerus. The tumor slowly grew up within
      ten years and become symptomatic with local pain, mild numbness in the
      distribution of the median nerve in the palm and Tinel's test. The tumor was
      successfully removed by separating it from the nerve fascicles to negative
      margins. Post-operatively local symptoms relieved but minor sensory loss in the
      median nerve distribution in the palm was noticed which improved in the following
      six months. Ancient schwannomas can be misdiagnosed as sarcomas due to specific
      imaging and histologic findings. Patients' physical examination, history and fine
      radiologic and pathology features should be cautiously interpreted in order to
      achieve correct diagnosis and avoid unnecessary wide tumor excisions.

PMID- 23546805
TI  - Lobomycosis successfully treated with posaconazole.
AB  - Lobomycosis is a chronic subcutaneous mycosis for which no standard treatment is
      available to date. We describe a patient in Peru with lobomycosis on the left
      earlobe that was successfully treated with posaconazole for 27 months. No
      evidence of recurrence was observed after five years of follow-up.

PMID- 23546804
TI  - Ecological suitability and spatial distribution of five Anopheles species in
      Amazonian Brazil.
AB  - Seventy-six sites characterized in Amazonian Brazil revealed distinct habitat
      diversification by examining the environmental factors associated with the
      distribution and abundance of five anopheline species (Diptera: Culicidae) in the
      subgenus Nyssorhynchus. These included three members of the Albitarsis Complex,
      Anopheles oryzalimnetes, Anopheles marajoara, Anopheles janconnae; Anopheles
      triannulatus, and Anopheles goeldii. Anopheles janconnae abundance had a positive
      correlation to water flow and a negative relationship to sun exposure. Abundance
      of An. oryzalimentes was associated with water chemistry. Anopheles goeldii
      larvae were abundant in shaded, more saline waters. Anopheles marajoara and An.
      triannulatus were negatively associated with available resources, although An.
      marajoara also showed several local correlations. These analyses suggest An.
      triannulatus is a habitat generalist, An. oryzalimentes and An. janconnae are
      specialists, and An. marajoara and An. goeldii could not be easily classified
      either way. Correlations described herein provide testable hypotheses for future
      research and identifying habitats for vector control.

PMID- 23546806
TI  - A systematic review of the literature on cystic echinococcosis frequency
      worldwide and its associated clinical manifestations.
AB  - A systematic literature review of cystic echinoccocosis (CE) frequency and
      symptoms was conducted. Studies without denominators, original data, or using one
      serological test were excluded. Random-effect log-binomial models were run for CE
      frequency and proportion of reported symptoms where appropriate. A total of 45
      and 25 articles on CE frequency and symptoms met all inclusion criteria.
      Prevalence of CE ranged from 1% to 7% in community-based studies and incidence
      rates ranged from 0 to 32 cases per 100,000 in hospital-based studies. The CE
      prevalence was higher in females (Prevalence Proportion Ratio: 1.35 [95% Bayesian
      Credible Interval: 1.16-1.53]) and increased with age. The most common
      manifestations of hepatic and pulmonary CE were abdominal pain (57.3% [95%
      confidence interval [CI]: 37.3-76.1%]) and cough (51.3% [95% CI: 35.7-66.7%]),
      respectively. The results are limited by the small number of unbiased studies.
      Nonetheless, the age/gender prevalence differences could be used to inform future
      models of CE burden.

PMID- 23546807
TI  - Placental malaria in Colombia: histopathologic findings in Plasmodium vivax and
      P. falciparum infections.
AB  - Studies on gestational malaria and placental malaria have been scarce in malaria
      endemic areas of the Western Hemisphere. To describe the histopathology of
      placental malaria in Colombia, a longitudinal descriptive study was conducted. In
      this study, 179 placentas were studied by histologic analysis (112 with
      gestational malaria and 67 negative for malaria). Placental malaria was confirmed
      in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical
      malaria-associated changes were observed in 37%. The most common changes were
      villitis, intervillitis, deciduitis, increased fibrin deposition, increased
      syncytial knots, mononuclear (monocytes/macrophages and lymphocytes),
      polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No
      association was found between type of placental changes observed and
      histopathologic classification of placental malaria. The findings are consistent
      with those reported for placental malaria in other regions. Plasmodium vivax was
      the main parasite responsible for placental and gestational malaria, but its role
      in the pathogenesis of placental malaria was not conclusive.

PMID- 23546808
TI  - Incidental focal FDG uptake in heart is a lighthouse for considering cardiac
      screening.
AB  - OBJECTIVES: Cardiac FDG uptake is known to show a variety of patterns under
      clinical fasting conditions. We hypothesized that focal FDG uptake in the heart
      (FUH) represents a sign of cardiac disease risk, especially in coronary artery
      disease (CAD).The aim of this study was to clarify the relationship between FUH
      and cardiac disease. METHODS: Cases showing FUH were selected based on comments
      in diagnostic reports or identification on retrospective review. Quantitative
      analysis was performed using maximum standardized uptake value (SUVmax), with
      regions of interest drawn over focal uptake areas in the heart as confirmed by
      PET/CT and in lateral side of the same slice showing focal FDG uptake. RESULTS:
      For the 20 patients (11 men, 9 women) with confirmed FUH, coronary artery
      stenosis or history of treatment for coronary disease was present in 11 patients
      (55.0 %), and 2 patients showed apical hypertrophy. Mean SUVmax of FUH did not
      differ significantly between patients with confirmed cardiac disease and those
      with no evidence of cardiac disease (P = 0.78). CONCLUSIONS: FUH suggests a high
      likelihood of CAD in patients without myocardial symptoms. Cardiac screening or a
      check of the history of cardiac disease is thus worth considering when FUH is
      seen incidentally on FDG-PET/CT.

PMID- 23546809
TI  - Platelet activity in Chinese obese adolescents with and without insulin
      resistance.
AB  - To investigate the platelet activity in Chinese obese adolescents with and
      without insulin resistance. A cross-sectional study was performed in 159 obese
      Chinese adolescents to investigate their platelet activity using anthropometrics
      and biochemical parameters, oral glucose tolerance test and platelet testing. An
      index of insulin sensitivity, homeostasis model assessment of insulin resistance
      (HOMA-IR), and plasma fibrinogen, prothrombin fragment 1.2 (PT 1.2),
      fibrinopeptide A (FPA) and the levels of aggregation to collagen 1 MUg/ml,
      adenosine diphosphate (ADP) 10 MUmol/L and arachidonic acid (AA) 0.5 mmol/L were
      measured. Obese adolescents with insulin resistance had significantly higher HOMA
      IR, glucose response curve (AUC), insulin AUC, PT 1.2, FPA and fibrinogen and
      aggregation (to collagen 1 MUg/ml, ADP 10 MUmol/L and AA 0.5 mmol/L) comparison
      with obese adolescents without insulin resistance (P < 0.05). Moreover, a
      positive correlation was found between both aggregation (to collagen, ADP and AA)
      and HOMA-IR (rho = 0.716; P < 0.01, rho = 0.682; P < 0.01 and rho = 0.699; P <
      0.01, respectively), glucose AUC (rho = 0.479; P < 0.01, rho = 0.416; P < 0.01
      and rho = 0.458; P < 0.01, respectively) and insulin AUC (rho = 0.585; P < 0.01,
      rho = 0.511; P < 0.01 and rho = 0.576; P < 0.01, respectively) in obese
      adolescents with insulin resistance. Insulin resistance is a major determinant of
      platelet activation in Chinese obese adolescents. 

PMID- 23546810
TI  - Selection of an autochthonous Saccharomyces strain starter for alcoholic
      fermentation of Sherry base wines.
AB  - Several indigenous Saccharomyces strains from musts were isolated in the Jerez de
      la Frontera region, at the end of spontaneous fermentation, in order to select
      the most suitable autochthonous yeast starter, during the 2007 vintage. Five
      strains were chosen for their oenological abilities and fermentative kinetics to
      elaborate a Sherry base wine. The selected autochthonous strains were
      characterized by molecular methods: electrophoretic karyotype and random
      amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) and by
      physiological parameters: fermentative power, ethanol production, sugar
      consumption, acidity and volatile compound production, sensory quality, killer
      phenotype, desiccation, and sulphur dioxide tolerance. Laboratory- and pilot
      scale fermentations were conducted with those autochthonous strains. One of them,
      named J4, was finally selected over all others for industrial fermentations. The
      J4 strain, which possesses exceptional fermentative properties and oenological
      qualities, prevails in industrial fermentations, and becomes the principal
      biological agent responsible for winemaking. Sherry base wine, industrially
      manufactured by means of the J4 strain, was analyzed, yielding, together with its
      sensory qualities, final average values of 0.9 g/l sugar content, 13.4 % (v/v)
      ethanol content and 0.26 g/l volatile acidity content; apart from a high
      acetaldehyde production, responsible for the distinctive aroma of "Fino". This
      base wine was selected for "Fino" Sherry elaboration and so it was fortified; it
      is at present being subjected to biological aging by the so-called "flor" yeasts.
      The "flor" velum formed so far is very high quality. To the best of our
      knowledge, this is the first study covering from laboratory to industrial scale
      of characterization and selection of autochthonous starter intended for alcoholic
      fermentation in Sherry base wines. Since the 2010 vintage, the indigenous J4
      strain is employed to industrially manufacture a homogeneous, exceptional Sherry
      base wine for "Fino" Sherry production.

PMID- 23546811
TI  - A Large Intragenic Deletion in the ACADM Gene Can Cause MCAD Deficiency but is
      not Detected on Routine Sequencing.
AB  - We report of a family who has three members affected by medium-chain acyl-CoA
      dehydrogenase (MCAD) deficiency, one of whom sadly died in the neonatal period
      prior to diagnosis. Routine sequencing, available on a service basis in the UK,
      identified only a heterozygous mutation in ACADM gene (c.985A>G, p.Lys329Glu) in
      this family. Linkage analysis suggested a possible intragenic deletion which was
      confirmed by the use of array-based comparative genomic hybridization (aCGH).
      This second mutation was a large intragenic deletion encompassing at least exons
      1-6 of the ACADM gene. Now that this deletion has been identified, several family
      members have come forward for carrier testing which was not possible previously.
      Larger deletions (20bp or more) have only previously been reported twice, but
      these may be a more frequent cause of MCAD deficiency than hitherto believed, due
      to fact that these are not anticipated and, therefore, the routine diagnostic
      techniques used will not identify them. This finding represents a useful learning
      point in the management of families with MCAD deficiency, and highlights that we
      should be routinely looking for larger deletions, when only one of the mutations
      can be identified on standard sequencing. 

PMID- 23546812
TI  - Motor and speech disorders in classic galactosemia.
AB  - Purpose To test the hypothesis that children with classic galactosemia and speech
      disorders are at risk for co-occurring strength and coordination disorders.
      Method This is a case-control study of 32 children (66% male) with galactosemia
      and neurologic speech disorders and 130 controls (50% male) ages 4-16 years.
      Speech was assessed using the Percentage of Consonants Correct (PCC) metric from
      responses to the Goldman-Fristoe Test of Articulation-2 and from a 5-min recorded
      speech sample, hand and tongue strength using the Iowa Oral Performance
      Instrument, and coordination using the Movement Assessment Battery for Children.
      The number of days on milk during the neonatal period was obtained by parent
      report. Analyses of covariance, distributions, and correlations were used to
      evaluate relationships among speech, strength, coordination, age, gender, and
      days on milk. Results Children with galactosemia had weaker hand and tongue
      strength and most (66%) had significant coordination disorders, primarily
      affecting balance and manual dexterity. Among children with galactosemia,
      children with more speech errors and classified as childhood apraxia of speech (n
      = 7) and ataxic dysarthria (n = 1), had poorer balance and manual dexterity, but
      not weaker hand or tongue strength, compared to the children with fewer speech
      errors. The number of days on milk during the neonatal period was associated with
      more speech errors in males but not in females. Conclusion Children with
      galactosemia have a high prevalence of co-occurring speech, coordination, and
      strength disorders, which may be evidence of a common underlying etiology, likely
      associated with diffuse cerebellar damage, rather than distinct disorders. 

PMID- 23546813
TI  - Defect of cobalamin intracellular metabolism presenting as diabetic ketoacidosis:
      a rare manifestation.
AB  - Hypoglycemia is the usual feature of commonly occurring organic acidemias.
      Organic acidemias manifesting as hyperglycemia or diabetic ketoacidosis are rare
      and only a few cases have been reported. We report a 13-month-old boy who
      presented with vomiting, dehydration, coma, hyperglycemia, high anion gap
      metabolic acidosis and ketosis, mimicking diabetic ketoacidosis (DKA). Treatment
      with parenteral fluid, electrolytes, and insulin infusion resulted in an
      improvement in hyperglycemia, but persistence of metabolic acidosis and lack of
      improvement of neurologic status led us to suspect an organic acidemia. Urinary
      organic acid analysis revealed increased methylmalonic acid levels. In addition,
      hyperhomocysteinemia and homocystinuria were also noted in presence of normal
      vitamin B12 levels. This confirmed the diagnosis of cobalamin metabolism defect
      leading to combined methylmalonic aciduria and homocystinuria. There was some
      improvement in neurologic status and metabolic parameters after treatment with
      low-protein diet, vitamin B12, folic acid, and L-carnitine, but he ultimately
      succumbed to polymicrobial nosocomial sepsis. The entire MMACHC gene of the
      patient was sequenced and no mutations were identified. This is probably the
      first case report of cobalamin intracellular metabolism defect
      (CblC/CblD/CblF/CblJ or ABCD4) presenting as diabetic ketoacidosis. 

PMID- 23546814
TI  - Early cardiac changes in children with anderson-fabry disease.
AB  - OBJECTIVE: Limited evidence is available about the early cardiac manifestation of
      Fabry disease (FD) in children. We aimed to evaluate cardiac involvement in
      children with FD by analysing serial structural and electrocardiographic changes.
      METHODS: The data were acquired from 22 children with FD [11 males; median age
      9.8 (ranging 2.5-16) years]. Seven patients (5 males) were on enzyme replacement
      therapy (ERT) with Agalasidase alpha. Echocardiography, ECG and 24-h ECG
      monitoring recordings were acquired during routine annual clinical controls. ECG
      data were compared to a group of age-and gender-matched controls. RESULTS: At
      baseline, ECG and ECHO parameters of left ventricular mass were similar in both
      males and females. Three boys (all were on ERT) developed left ventricular
      hypertrophy (LVH) during two-year follow-up. The progression to LVH was
      accompanied by the appearance of frequent ventricular premature beats in two
      cases and supraventricular premature beats (SPBs) with T wave inversion in one
      case. T wave inversion and SPBs were detected in two younger relatives of a
      patient with LVH, in the absence of detectable LVH. Seven out of 22 patients had
      T wave abnormalities. Five of them were males (p = 0.03) all carrying the N215S
      mutation (p = 0.03). At baseline, median PR intervals were prolonged in FD
      subjects compared to controls [143 (122-177) vs. 122 (82-165) ms; p < 0.0001].
      CONCLUSIONS: Cardiac complications of FD become apparent in childhood as subtle
      changes with slow but detectable progression over time, with males more
      frequently affected than females. Progression of LVH was apparent in three
      children despite ERT.

PMID- 23546817
TI  - Dynamic live imaging of bone: opening a new era with 'bone histodynametry'.
AB  - Recent advances in optical imaging with two-photon excitation microscopy have
      enabled visualization of the inside of intact bone tissues in living animals.
      Using these advanced techniques, the dynamic behaviors of live bone cells and
      static histological information on bone tissue structures can be elucidated. The
      migration and positioning of osteoclast precursor monocytes, the bone-resorbing
      function of mature osteoclasts, and its functional coupling with bone
      replenishing osteoblasts have been evaluated, including their dynamic properties
      in intact live bones. This novel 'bone histodynametric' methodology, combined
      with conventional histomorphometric analyses, will surely contribute to opening
      of a new era in bone and mineral research. 

PMID- 23546818
TI  - Vitamin D and calcium-sensing receptor polymorphisms differentially associate
      with resting energy expenditure in peripubertal children.
AB  - Given that calcium metabolism is influenced by genes and is tightly linked to
      energy-utilizing pathways, this study evaluated the association of single
      nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and calcium
      sensing receptor (CASR) with resting energy expenditure (REE). In 273 boys and
      girls, 7-12 years of age, cross-sectional REE was measured via indirect
      calorimetry, body composition by DXA, and dietary measures by 24-h recall. SNPs
      for VDR Cdx-2 (rs11568820) and CASR A986S (rs1801725) were genotyped using the
      Illumina Golden Gate assay. Multiple linear regression models were used to
      determine the association between SNPs and REE. African American carriers of the
      'A' VDR Cdx2 allele had increased levels of REE in the overall sample, and this
      association was apparent among participants with an adiposity level of <25 % and
      30 % body fat in males and females, respectively. For CASR, an association
      between carriers of the 'A' allele and REE was observed only in those in the
      upper median of calcium intake. VDR and CASR variants are associated with REE in
      children and are influenced by levels of calcium intake and adiposity. Our
      results bring awareness to mechanisms underlying the regulation of REE and
      biological and dietary influential factors. 

PMID- 23546819
TI  - The SERM raloxifene improves diaphyseal fracture healing in mice.
AB  - Although several studies reported that raloxifene treatment improves
      postmenopausal osteoporotic bone structure and reduces fracture risk, only a few
      animal and no human studies have examined its effects on the fracture healing
      process. Thus the aim of the present study was to determine, whether systemic
      application of the selective estrogen receptor modulator raloxifene promotes
      fracture healing compared to untreated control-, estrogen-deficient-, as well as
      estrogen-treated mice using a standardized femoral osteotomy model (n = 60 mice).
      Ten days after surgery, contact radiography and undecalcified histomorphometric
      analysis revealed that raloxifene administration significantly improved the early
      stage of fracture healing compared to all other groups. At day 20, raloxifene and
      estrogen treatment led to a significant increase in callus mineralization and
      trabecular thickness compared to control mice. MUCT analyses revealed no evidence
      of complete bony bridging of the fracture site in any control-, nor estrogen
      deficient mouse after 20 days, while all femoral fractures in the raloxifene and
      estrogen group already healed adequately at this time. These data indicate that
      raloxifene treatment significantly improves all phases of fracture healing at
      least in mice. Therefore, raloxifene could be a possible pharmaceutical to
      enhance fracture healing in women, without the known side effects of estrogen. 

PMID- 23546820
TI  - Do individuals with a family history of colorectal cancer adhere to medical
      recommendations for the prevention of colorectal cancer?
AB  - Individuals with a family history of colorectal cancer (CRC), have a two-to-five
      fold increased lifetime risk to develop CRC. Thus, they are particularly likely
      to benefit from adherence to medical recommendations for CRC prevention. Despite
      this increased risk, previous studies have shown an underutilization of
      colonoscopy for screening and a paucity of data on lifestyle habits that could
      enhance colonoscopy rates in this population. The primary aims were (a) to assess
      CRC screening patterns and lifestyle choices among siblings and children of CRC
      patients, (b) to ascertain discrepancies between actual behavior and medical
      recommendations, and (c) to identify family members with multiple unhealthy
      lifestyle habits. The secondary aim was to test for possible associations between
      utilization rates for CRC screening and other preventive health services. A cross
      sectional study was conducted among 318 first-degree relatives (FDRs) of 164 CRC
      patients treated at the Tel Aviv Sourasky Medical Center. Interviews were
      conducted with a structured questionnaire. There was significant underutilization
      of colonoscopy for screening with only 73 FDRs (23.0%) adhering to the
      recommended screening schedule. This rate was slightly improved (N = 58, 31.9%)
      among subjects aged 40 years and above, although it was still far below the
      optimum. A similar result (N = 70, 21.7%) was observed for other cancer screening
      tests and routine medical check-ups. A significant association (P < 0.0001) was
      found for healthful lifestyles, overall use of preventive health services, and
      adherence to CRC screening recommendations. CRC screening is significantly
      underutilized among FDRs of CRC patients. FDRs who do not comply with CRC
      screening guidelines, lead unhealthy lifestyles, and avoid other cancer screening
      tests are at increased risk and should be addressed specifically in future
      interventions.

PMID- 23546821
TI  - The history of Lynch syndrome.

PMID- 23546822
TI  - Dose-response relationships between physical activity, social participation, and
      health-related quality of life in colorectal cancer survivors.
AB  - PURPOSE: The purpose of this study was to examine the relationships between
      physical activity (PA), social participation, and health-related quality of life
      (HQOL) in older, long-term colorectal cancer survivors. METHODS: Male and female
      colorectal cancer survivors (n = 1,768), aged >=65 and >=5 years post-diagnosis,
      completed surveys on their current PA, social participation, HQOL, health
      history, and relevant covariates. Analysis of covariance was used to evaluate the
      cross-sectional relationship between PA and social participation with the SF-36
      subscales, as well as the physical component summary score (PCS) and mental
      health component summary score (MCS). RESULTS: The final analytic sample (n =
      832) was 81.5 +/- 5.8 years and 8.2 +/- 1.7 years post-diagnosis (mean +/- SD).
      Meeting the current recommendation of 150 min/week of PA was associated with
      higher PCS (p < 0.001) but not MCS (p = 0.30). Engaging in any social
      participation, vs. none, was associated with MCS (p = 0.003), but not PCS (p =
      0.13). There was a dose-response relationship between moderate-vigorous-intensity
      PA and PCS (p trend<0.001). Light-intensity PA was not associated with either
      summary score after adjustment for moderate-vigorous PA (p > 0.05), but in
      survivors performing no higher-intensity PA, it was associated with both (p <
      0.01, p = 0.02, respectively). Participants reporting greater amounts of both
      planned exercise and non-exercise PA had significantly higher PCS (p trend<0.01,
      p trend < 0.01, respectively). Individuals participating in greater weekly hours
      of social participation had higher PCS and MCS (p trend<0.05) than those
      participating in less. CONCLUSIONS: Among older, long-term colorectal cancer
      survivors, PA is related to their physical health, while social participation is
      predominantly related to their mental health. IMPLICATIONS FOR CANCER SURVIVORS:
      Older colorectal cancer survivors who participate socially and are engaged in PA,
      even non-exercise and light-intensity activities, have higher levels of physical
      and mental health.

PMID- 23546823
TI  - Features of perceived neighborhood environment associated with daily walking time
      or habitual exercise: differences across gender, age, and employment status in a
      community-dwelling population of Japan.
AB  - OBJECTIVE: Perceived neighborhood environment (NE) is considered a determinant of
      daily physical activity (PA). However, evidence concerning differences among
      types of PA, gender, and age is limited. The study purpose was to clarify the
      association between NE and walking time (WT) or habitual exercise (HE) across
      gender, age, and employment status in a community-dwelling population of Japan.
      METHODS: A questionnaire mail survey with a stratified random 7,515 sampling was
      conducted in a northeast city in January 2007. Multiple logistic analysis was
      conducted to examine the associations between seven NE indices and WT or HE
      across gender, age, and employment status: 20-39 (young-employed), 40-59 (middle
      employed), and 60-79 (old-employed or old-unemployed) after adjustment for age
      and means of transportation. RESULTS: A total of 3,806 residents (52.4 % females)
      completed the survey. Traffic and crime safety in old-unemployed males and
      proximity to service facilities and traffic and crime safety in middle-employed
      females were significantly associated with a low risk of insufficient WT.
      Proximity to service facilities in old-employed males, number of service
      facilities, places for walking, and good view in middle-employed females, and
      density of dwelling and proximity to service facilities in old-unemployed females
      were significantly associated with a low risk of non-HE. CONCLUSIONS: The
      association between NE and WT or HE differed across type of PA, gender, age, and
      employment status, and was observed mainly in middle- and old-aged females. The
      middle- and old-aged female residents' PA possibly were more influenced by their
      NE, and NE would contribute to promote active living.

PMID- 23546824
TI  - Inhibition of avian leukosis virus subgroup J replication by miRNA targeted
      against env.
AB  - No effective vaccine has been developed against the subgroup J avian leukosis
      virus (ALV-J). The genetic diversity of ALV-J might be related to the env gene,
      therefore, we selected conserved sequences of the env gene and designed
      interference sequence. In this study, microRNAs (miRNAs) were designed and
      synthesized, corresponding to conserved regions of the env gene. These miRNAs
      were cloned into the linearized eukaryotic expression vector. The recombinant
      plasmids were transfected into DF-1 cells. After transfection, the cells were
      inoculated with ALV-J. In reporter assays, the transfection efficiency is 80% by
      indirect immunofluorescence (IFA). Expression of the virus envelope glycoprotein
      was measured by IFA and western blotting assays. The relative expression of env
      gene was determined using quantitative PCR. Our results show that the mi-env 231
      and mi-env 1384 could effectively suppress the replication of ALV-J with an
      efficiency of 68.7-75.2%. These data suggest that the miRNAs targeting the env
      can inhibit replication of ALV-J efficiently. This finding provides evidence that
      miRNAs could be used as a potential tool against ALV infection.

PMID- 23546825
TI  - Complete genome sequence of enterovirus 87 isolated from a child with acute
      flaccid paralysis in China in 2000.
AB  - Enterovirus 87 (EV87) is a new member of species Human Enterovirus B. So far,
      only the genome sequence of the prototype strain from Bangladesh is available.
      Here, we report the genome sequence of EV87 strain LY02/SD/CHN/2000 isolated from
      an acute flaccid paralysis case in Shandong Province, China, in 2000. It has a
      genome of 7423 nucleotides. Compared with the prototype strain, it had 80.3%
      nucleotide and 95.5% amino acid similarity in the VP1 coding region and 82.8%
      complete genome similarity, reflecting distant genetic relationship between them.
      Phylogenetic analysis provided evidence of recombination with other serotypes in
      the P2 and P3 coding regions.

PMID- 23546826
TI  - Activity budget, diet, and use of space by two groups of squirrel monkeys
      (Saimiri sciureus) in eastern Amazonia.
AB  - Squirrel monkeys (Saimiri spp.) are widely distributed in the Amazon basin. This
      study describes the ecological and behavioral patterns of two social groups of S.
      sciureus in forests adjacent to the Tucurui hydroelectric reservoir in eastern
      Amazonia, including range size, activity budgets, and composition of the diet.
      The groups were monitored at Base 4 (group B4) and Germoplasma Island (group GI).
      Quantitative behavioral data were collected using instantaneous scan sampling to
      record behavior, substrate use, and height. Home ranges were delimited using a
      GPS to determine group position after each 50 m of movement. Home ranges were
      75.0 ha for group B4 (39 members) and 77.5 ha for group GI (32 members). The use
      of vertical strata was well defined, with a marked preference for the middle and
      lower levels of the canopy. The activity budgets of both groups were typical of
      those of other squirrel monkeys and were dominated by foraging (B4 = 48.7 %; GI =
      49.6 %), moving (both groups 28.9 %), and feeding (B4 = 14.6 %; GI = 12.4 %).
      Resting was rare (B4 = 3.5 %; GI = 2.6 %) and less common than social behavior
      (B4 = 4.3 %; GI = 6.4 %). The diet of both groups was dominated by plant material
      (B4 = 70.7 % of feeding records; GI = 71.4 %), which is in contrast with the more
      insectivorous diets recorded for Saimiri at other sites. Group GI spent more time
      foraging during the dry season, whereas group B4 spent more time in the rainy
      season when the consumption of fruit increased (significantly, in the case of
      group GI). The less insectivorous diet of these groups may be due to a number of
      factors, including the unique habitat configuration at the site and reduced
      hydrological stress due to the proximity of the reservoir.

PMID- 23546827
TI  - Current state of endovascular treatment for vasculogenic erectile dysfunction.
AB  - Normal erectile function requires adequate penile arterial inflow, normal penile
      architecture and an intact venous capacitance system. Vascular disease is the
      dominant etiology of erectile dysfunction (ED) and current medical therapy
      increases penile blood flow. However, in a large proportion of patients, medical
      therapy is inadequate or contraindicated requiring the use of mechanical
      constrictive devices or implantation of a penile prosthesis. Rapid advances in
      endovascular intervention have allowed safe and effective treatment of small
      arteries in other vascular beds. A minimally invasive approach targeting penile
      arterial inflow disease may prove to be safe and effective. In this paper, we
      discuss the normal arterial blood supply to the penis, describe angiographic
      findings in patients with ED, and critically review the published data on
      endovascular and microsurgical approaches at reestablishing penile blood flow.
      Lastly, we offer a potential algorithm and procedural tips for endovascular
      intervention for ED.

PMID- 23546828
TI  - Isolation of phytase-producing bacteria from Himalayan soils and their effect on
      growth and phosphorus uptake of Indian mustard (Brassica juncea).
AB  - Phytase-producing bacteria (PPB) is being investigated as plant growth promoting
      rhizobacteria (PGPR) to improve the phosphorus (P) nutrition and growth of plants
      grown in soil with high phytate content. Phytate is dominant organic P forms in
      many soils and must be hydrolyzed to be available for plants. Indian mustard
      (Brassica juncea) is a plant with economic importance in agriculture and
      phytoremediation, therefore biotechnological tools to improve growth and
      environmental stress tolerance are needed. In this study, we isolated and
      characterized PPB from Himalayan soils and evaluated their effect on growth and P
      uptake by B. juncea under greenhouse conditions. Sixty five PPB were isolated and
      based on phytate hydrolysis, three efficient PPB were chosen and identified as
      Acromobacter sp. PB-01, Tetrathiobacter sp. PB-03 and Bacillus sp. PB-13.
      Selected PPB showed ability to grow at wide range of pH, temperature and salt
      concentrations as well as to harbour diverse PGPR activities, such as:
      solubilization of insoluble Ca-phosphate (193-642 MUg ml(-1)), production of
      phytohormone indole acetic acid (5-39 MUg ml(-1)) and siderophore.
      Tetrathiobacter sp. PB-03 and Bacillus sp. PB-13 showed 50 and 70 % inhibition of
      phytopathogen Rhizoctonia solani, respectively. Greenhouse potting assay also
      showed that the bacterization of B. juncea seeds with Tetrathiobacter sp. PB-03
      and Bacillus sp. PB-13 significantly increased the biomass and P content in 30
      days old seedlings. This study reveals the potential of PPB as PGPR to improve
      the growth of B. juncea.

PMID- 23546829
TI  - Patagonian red wines: selection of Lactobacillus plantarum isolates as potential
      starter cultures for malolactic fermentation.
AB  - The aim of this study was to evaluate fifty-three Lactobacillus plantarum
      isolates obtained from a Patagonian red wine, molecularly identified and typified
      using RAPD analysis, in order to select starter cultures for malolactic
      fermentation (MLF). The results obtained suggest a considerable genetic
      diversity, taking into account that all L. plantarum isolates were obtained from
      one cellar and one vintage. Based on the capacity to tolerate a concentration of
      14 % ethanol in MRS broth for 2 days, eight isolates were selected for the
      subsequent analysis. The incidence of various wine stress factors (ethanol, acid
      pH, lysozyme and sulfur dioxide) on isolates growth was studied. Besides,
      glucosidase and tannase activities were evaluated, and the presence of genes
      involved in the synthesis of biogenic amines was examined by PCR. A previously
      characterized indigenous Oenococcus oeni strain was included with comparative
      purposes. Differences in technologically relevant characteristics were observed
      among the eight L. plantarum selected isolates, revealing an isolate-dependent
      behavior. Detectable glucosidase and tannase activities were found in all
      isolates. The presence of genes encoding histidine and tyrosine descarboxylases
      and putrescine carbamoyltransferase was not detected. The ability of L. plantarum
      isolates to grow and consume L-malic acid in simulated laboratory-scale
      vinifications revealed that two of them could be considered as possible MLF
      starter cultures for Patagonian red wines. These isolates will be subjected to
      further analysis, for a final winery technological characterization. 

PMID- 23546830
TI  - Immobilization and characterization of carbonic anhydrase purified from E. coli
      MO1 and its influence on CO2 sequestration.
AB  - The present investigation entails the immobilisation and characterisation of
      Escherichia coli MO1-derived carbonic anhydrase (CA) and its influence on the
      transformation of CO2 to CaCO3. CA was purified from MO1 using a combination of
      Sephadex G-75 and DEAE cellulose column chromatography, resulting in 4.64-fold
      purification. The purified CA was immobilised in chitosan-alginate
      polyelectrolyte complex (C-A PEC) with an immobilisation potential of 94.5 %.
      Both the immobilised and free forms of the enzyme were most active and stable at
      pH 8.2 and at 37  degrees C. The K(m) and V(max) of the immobilised enzyme were
      found to be 19.12 mM and 416.66 MUmol min-1 mg-1, respectively; whereas, the K(m)
      and V(max) of free enzyme were 18.26 mM and 434.78 MUmol min-1 mg-1,
      respectively. The presence of metal ions such as Cu2+, Fe2+, and Mg2+ stimulated
      the enzyme activity. Immobilised CA showed higher storage stability and
      maintained its catalytic efficiency after repeated operational cycles.
      Furthermore, both forms of the enzyme were tested for targeted application of the
      carbonation reaction to convert CO2 to CaCO3. The amounts of CaCO3 precipitated
      over free and immobilised CA were 267 and 253 mg/mg of enzyme, respectively. The
      results of this study show that immobilised CA in chitosan-alginate beads can be
      useful for CO2 sequestration by the biomimetic route.

PMID- 23546831
TI  - Germination and proliferation of emetic Bacillus cereus sensu lato strains in
      milk.
AB  - The Bacillus cereus sensu lato group includes potentially pathogenic bacteria
      that are ubiquitous in the environment and, importantly, could also be present in
      food products. This study focuses on emetic isolates which presumably could cause
      acute food poisoning and emetic syndrome. Here, we evaluate the ability of
      psychrotolerant Bacillus weihenstephanensis MC118 (isolated from soil) and
      mesophilic B. cereus BOD3/9 isolated from milk to germinate and multiply at 7 and
      30  degrees C. Whereas the rates of germination at 30  degrees C in milk and
      nutrient broth of MC118 and BOD3/9 were similar, MC118, but not BOD3/9,
      proliferated to achieve relatively high numbers (~10(6) colony-forming units/g)
      within 7 days of incubation at 7  degrees C. Mesophilic BOD3/9 showed a slight
      decrease of cell concentration in similar studies at 7  degrees C. Genotyping
      with repetitive extragenic palindromic sequence-based PCR and pulsed field gel
      electrophoresis revealed significant similarities between BOD3/9 and emetic
      reference B. cereus F4810/72 strain, while the B. weihenstephanensis MC118
      isolate was more similar to the B. weihenstephanensis non-emetic reference
      DSMZ11821 strain. Our data suggest that emetic isolates that are also
      psychrotolerant, such as MC118, could constitute a hazard in the dairy industry,
      where milk could be a suitable medium for germination and growth. 

PMID- 23546834
TI  - Deadly distractions.
AB  - In 2011, the National Transportation Safety Board urged all states to ban the use
      of portable electronic devices while driving, including hand-held and hands-free
      devices. Texting while driving concerns several Texas legislators, who have filed
      bills, backed by the Texas Medical Association, to ban the practice. TMA
      physicians recognize that the use of hand-held and hands-free devices and other
      factors associated with distracted driving affect their patients' safety.

PMID- 23546833
TI  - Identification of a New Delhi metallo-beta-lactamase-4 (NDM-4)-producing
      Enterobacter cloacae from a Czech patient previously hospitalized in Sri Lanka.

PMID- 23546832
TI  - Light regulation on growth, development, and secondary metabolism of marine
      derived filamentous fungi.
AB  - Effects of different light conditions on development, growth, and secondary
      metabolism of three marine-derived filamentous fungi were investigated. Darkness
      irritated sexual development of Aspergillus glaucus HB1-19, while white, red, and
      blue lights improved its asexual behavior. The red and blue lights improved
      asexual stroma formation of Xylaria sp. (no. 2508), but the darkness and white
      light inhibited it. Differently, development of Halorosellinia sp. (no. 1403)
      turned out to be insensitive to any tested light irradiation. Upon the
      experimental data, no regularity was observed linking development with secondary
      metabolism. However, fungal growth showed inversely correlation with productions
      of major bioactive compounds (aspergiolide A, 1403C, and xyloketal B) from
      various strains. The results indicated that aspergiolide A biosynthesis favored
      blue light illumination, while 1403C and xyloketal B preferred red light
      irradiation. With the favorite light sensing conditions, productions of
      aspergiolide A, 1403C, and xyloketal B were enhanced by 32.9, 21.9, and 30.8 %
      compared with those in the dark, respectively. The phylogenetic analysis
      comparing the light-responding proteins of A. glaucus HB 1-19 with those in other
      systems indicated that A. glaucus HB 1-19 was closely related to Aspergillus spp.
      especially A. nidulans in spite of its role of marine-derived fungus. It
      indicated that marine fungi might conserve its light response system when
      adapting the marine environment. This work also offers useful information for
      process optimization involving light regulation on growth and metabolism for drug
      candidate production from light-sensitive marine fungi. 

PMID- 23546835
TI  - Turning the corner.
AB  - Physicians have encountered various problems since Novitas Solutions Inc. took
      over from TrailBlazer last November as the Texas Medicare carrier. Novitas
      representatives acknowledge the company fell short in some areas, with customer
      service challenges and delays in appeals processing being the main ones. Texas
      Medical Association's Payment Advocacy staff members continue to closely monitor
      Novitas' operations. They remain in regular conversations with the carrier and
      the Centers for Medicare & Medicaid Services, which approved Novitas as the
      regional Medicare contractor in 2011.

PMID- 23546836
TI  - Preparing for the worst.
AB  - Unexpected deaths profoundly impact those left behind. And in the case of
      physicians, their deaths have financial and business implications they must
      address in advance. Professional planning allows physicians to address call
      coverage, management, and administration of the medical practice and helps ensure
      the orderly continuation of practice operations.

PMID- 23546837
TI  - Measure of success.

PMID- 23546839
TI  - Proton beam radiation therapy for prostate cancer-is the hype (and the cost)
      justified?
AB  - Although in use for over 40 years, proton beam therapy for prostate cancer has
      only recently come under public scrutiny, due to its increased cost compared to
      other forms of treatment. While the last decade has seen a rapid accumulation of
      evidence to suggest that proton beam therapy is both safe and effective in this
      disease site, a rigorous comparison to other radiotherapy techniques has not yet
      been completed. In this review, we provide an in-depth look at the evidence both
      supporting and questioning proton beam therapy's future role in the treatment of
      prostate cancer, with emphasis on its history, physical properties, comparative
      clinical and cost effectiveness, advances in its delivery and future promise.

PMID- 23546840
TI  - Unique substrate specificity of purine nucleoside phosphorylases from Thermus
      thermophilus.
AB  - The degradation of purine nucleoside is the first step of purine nucleoside
      uptake. This degradation is catalyzed by purine nucleoside phosphorylase, which
      is categorized into two classes: hexameric purine nucleoside phosphorylase (6PNP)
      and trimeric purine nucleoside phosphorylase (3PNP). Generally, 6PNP and 3PNP
      degrade adenosine and guanosine, respectively. However, the substrate specificity
      of 6PNP and 3PNP of Thermus thermophilus (tt6PNP and tt3PNP, respectively) is the
      reverse of that anticipated based on comparison to other phosphorylases.
      Specifically, in this paper we reveal by gene disruption that tt6PNP and tt3PNP
      are discrete enzymes responsible for the degradation of guanosine and adenosine,
      respectively, in T. thermophilus HB8 cells. Sequence comparison combined with
      structural information suggested that Asn204 in tt6PNP and Ala196/Asp238 in
      tt3PNP are key residues for defining their substrate specificity. Replacement of
      Asn204 in tt6PNP with Asp changed the substrate specificity of tt6PNP to that of
      a general 6PNP. Similarly, substitution of Ala196 by Glu and Asp238 by Asn
      changed the substrate specificity of tt3PNP to that of a general 3PNP. Our
      results indicate that the residues at these positions determine substrate
      specificity of PNPs in general. Sequence analysis further suggested most 6PNP and
      3PNP enzymes in thermophilic species belonging to the Deinococcus-Thermus phylum
      share the same critical residues as tt6PNP and tt3PNP, respectively.

PMID- 23546841
TI  - Broad nucleotide cofactor specificity of DNA ligase from the hyperthermophilic
      crenarchaeon Hyperthermus butylicus and its evolutionary significance.
AB  - The nucleotide cofactor specificity of the DNA ligase from the hyperthermophilic
      crenarchaeon Hyperthermus butylicus (Hbu) was studied to investigate the
      evolutionary relationship of DNA ligases. The Hbu DNA ligase gene was expressed
      under control of the T7lac promoter of pTARG in Escherichia coli BL21
      CodonPlus(DE3)-RIL. The expressed enzyme was purified using the IMPACTTM-CN
      system (intein-mediated purification with an affinity chitin-binding tag) and
      cation-ion (Arg-tag) chromatography. The optimal temperature for Hbu DNA ligase
      activity was 75  degrees C, and the optimal pH was 8.0 in Tris-HCl. The activity
      was highly dependent on MgCl2 or MnCl2 with maximal activity above 5 mM MgCl2 and
      2 mM MnCl2. Notably, Hbu DNA ligase can use ADP and GTP in addition to ATP. The
      broad nucleotide cofactor specificity of Hbu DNA ligase might exemplify an
      undifferentiated ancestral stage in the evolution of DNA ligases. This study
      provides new evidence for possible evolutionary relationships among DNA ligases.

PMID- 23546844
TI  - Feasibility of interactive text message response (ITR) as a novel, real-time
      measure of adherence to antiretroviral therapy for HIV+ youth.
AB  - Youth living with HIV/AIDS (YLH) face unique challenges to optimal adherence to
      antiretroviral therapy (ART). Accurate, real-time methods to assess adherence are
      needed to facilitate early intervention and promote viral suppression. The
      purpose of this study was to assess the feasibility and validity of interactive
      text message response (ITR) as a measure of adherence to ART among YLH. This
      study was part of a larger pilot text message reminder intervention conducted at
      a US community-based, LGBT-focused health center providing clinical services to
      YLH. Eligibility criteria for this pilot study included HIV-positive serostatus,
      aged 14-29, use of personal cell phone, English-speaking, and on ART with
      demonstrated adherence difficulties. During the 24-week study period,
      participants received personalized daily short message system reminders with a
      follow-up message 1 hour later asking whether they took medication and directing
      a response via return text message. To determine whether or not ITR would be a
      feasible, valid measure of adherence, we calculated the proportion of positive
      responses indicating medication had been taken divided by the total number of
      messages requesting a response and compared this response rate to a self-reported
      adherence measure, the visual analogue scale (VAS). Participants (n = 25) were on
      average 23 years old, largely male (92%), Black (60%) and behaviorally infected
      (84%). Over the course of the intervention, study participants responded to
      prompts via text to indicate whether or not they had taken their medication
      approximately 61% of the time. The overall mean ITR adherence rate (i.e.,
      positive responses) was 57.4% (SD = 28.5%). ITR and VAS measures were moderately,
      positively correlated (r = 0.52, p < 0.05) during the first 6 weeks of the study
      period. ITR adherence rates were significantly higher on weekdays versus weekends
      (p < 0.05). This pilot study showed both moderate responsiveness of individuals
      to daily ITR and a moderate correlation of ITR adherence rates with a reliable
      measure during the first 6 weeks of the study, suggesting that this method, with
      additional effort and improvements, may be a helpful tool to identify and respond
      to adherence patterns in real-time.

PMID- 23546845
TI  - Combined sonographic testing index and prediction of adverse outcome in preterm
      fetal growth restriction.
AB  - OBJECTIVE: We sought to test the hypothesis that a combined sonographic scoring
      system (CSTI) that incorporates features of the biophysical profile (BPP) and
      multivessel Doppler evaluation improves prediction of adverse outcomes in preterm
      intrauterine growth restriction. METHODS: This was a prospective cohort study of
      growth-restricted fetuses with abnormal umbilical artery (UA) Doppler studies,
      defined as pulsatility index (PI) > 95 th percentile for gestational age or
      absent/reversed end diastolic flow. Fetuses were followed with weekly BPP and
      Doppler evaluation of the UA, middle cerebral artery (MCA), and ductus venosus
      (DV) until the time of delivery. The cerebroplacental Doppler ratio (CPR) was
      then calculated (MCA PI/UA PI). MCA PI < 5 th percentile, MCA peak systolic
      velocity (PSV) > 1.5 multiples of the median, DV PI > 95 th percentile with or
      without absent/reversed flow, and CPR < 1.08 were considered abnormal. Using
      logistic regression modeling, a weighted scoring index for the prediction of a
      composite fetal vulnerability index (FVI), which included 5-minute Apgar score <
      3, cord pH < 7.2, seizures, necrotizing enterocolitis, grade 4 intraventricular
      hemorrhage, periventricular leukomalacia, and neonatal death, was developed. A
      receiver operating characteristic (ROC) curve was used to identify the best score
      associated with the FVI. RESULTS: Of 66 patients meeting inclusion criteria over
      a 5-year period, 17 (25.8%) had a positive FVI. Abnormal BPP (< 8), MCA PI, MCA
      PSV, DV PI, and CPR were observed in 6, 27.3, 13.6, 56.1, and 33.3% of patients,
      respectively. From the logistic regression model, a CSTI was developed including
      a score of 1 for abnormal BPP, 3 for MCA PSV, 1 for DV, 6 for CPR, and 3 for
      oligohydramnios. The ROC curve identified a score of >= 7 to be the best
      predictor of FVI with sensitivity of 35.1% and specificity of 91.8% and a
      positive likelihood ratio of 4.3 (area under ROC curve 0.73). These test
      characteristics were better than those for any of the individual component
      antenatal tests. CONCLUSION: Although this novel scoring system performs modestly
      in predicting adverse outcomes in FGR, it appears to perform better than any
      individual antenatal test currently available.

PMID- 23546846
TI  - Neonatal morbidity by week of gestational age for twins compared to singletons: a
      population-based cohort study.
AB  - OBJECTIVE: Quantify neonatal morbidity by week of gestation for twins compared
      with singletons. STUDY DESIGN: We performed a population-based retrospective
      cohort study of all Ohio births from 2006 to 2007. Composite neonatal morbidity
      consisting of Apgar score < 7 at 5 minutes, assisted ventilation > 6 hours,
      neonatal transport, or seizures was compared between singletons and twins from 34
      to 41 weeks. RESULTS: Neonatal morbidity was the lowest in twins delivered at 37
      completed weeks and 2 weeks later for singletons at 39 weeks. Twin morbidity
      rapidly increased after 37 weeks and reached 15.8% at 41 weeks versus the
      singleton morbidity rate of 3.4% at 41 weeks. Twins delivered at 39 weeks and
      beyond were more than twice as likely to incur neonatal morbidity compared with
      singletons. CONCLUSION: The lowest rate of neonatal morbidity occurs at 37 weeks
      for twins versus 39 weeks for singleton births. The increased risk after 37 weeks
      for twins accelerates at a faster rate compared with that for singletons born
      past 39 weeks.

PMID- 23546842
TI  - Purinergic signalling and diabetes.
AB  - The pancreas is an organ with a central role in nutrient breakdown, nutrient
      sensing and release of hormones regulating whole body nutrient homeostasis. In
      diabetes mellitus, the balance is broken-cells can be starving in the midst of
      plenty. There are indications that the incidence of diabetes type 1 and 2, and
      possibly pancreatogenic diabetes, is rising globally. Events leading to insulin
      secretion and action are complex, but there is emerging evidence that
      intracellular nucleotides and nucleotides are not only important as intracellular
      energy molecules but also as extracellular signalling molecules in purinergic
      signalling cascades. This signalling takes place at the level of the pancreas,
      where the close apposition of various cells-endocrine, exocrine, stromal and
      immune cells-contributes to the integrated function. Following an introduction to
      diabetes, the pancreas and purinergic signalling, we will focus on the role of
      purinergic signalling and its changes associated with diabetes in the pancreas
      and selected tissues/organ systems affected by hyperglycaemia and other stress
      molecules of diabetes. Since this is the first review of this kind, a
      comprehensive historical angle is taken, and common and divergent roles of
      receptors for nucleotides and nucleosides in different organ systems will be
      given. This integrated picture will aid our understanding of the challenges of
      the potential and currently used drugs targeted to specific organ/cells or
      disorders associated with diabetes.

PMID- 23546847
TI  - Association between measures of patella height, morphologic features of the
      trochlea, and patellofemoral joint alignment: the MOST study.
AB  - BACKGROUND: Patellofemoral joint (PFJ) malalignment (lateral patella displacement
      and tilt) has been proposed as a cause of patellofemoral pain. Patella height
      and/or the morphologic features of the femoral trochlea may predispose one to
      patella malalignment. QUESTIONS/PURPOSES: The purposes of our study were to
      assess the associations among patella height, morphologic features of the
      trochlea, and measures of PFJ alignment and to determine which measures of
      patella height and morphologic features of the trochlea were the best predictors
      of PFJ alignment. METHODS: Measures of patella height (Insall-Salvati ratio and
      modified Insall-Salvati ratio), morphologic features of the trochlea (sulcus
      angle, trochlear angle, lateral trochlear inclination, medial trochlear
      inclination), and PFJ alignment (bisect offset and patella tilt angle) were
      assessed in 566 knees from the Multicenter Osteoarthritis Study. RESULTS: Bisect
      offset was correlated with the Insall-Salvati ratio (r = 0.25) and lateral
      trochlear inclination (r = -0.38). Patella tilt angle correlated with the
      trochlear angle (-0.27) and lateral trochlear inclination (-0.32). Linear
      regression models including the Insall-Salvati ratio and lateral trochlear
      inclination explained 20% and 11% of the variance in bisect offset and patella
      tilt angle, respectively. CONCLUSIONS: Of the variables measured in the current
      study, the Insall-Salvati ratio and lateral trochlear inclination were the best
      predictors of lateral patella displacement and lateral tilt. This knowledge will
      aid clinicians in the identification of anatomic risk factors for PFJ
      malalignment and/or PFJ dysfunction.

PMID- 23546848
TI  - Editor's spotlight/Take 5: Orthopaedic surgeons frequently underestimate the cost
      of orthopaedic implants (DOI 10.1007/s11999-012-2757-x).

PMID- 23546849
TI  - Fee-based care is important for access to prompt treatment of hip fractures among
      veterans.

PMID- 23546850
TI  - Does early functional outcome predict 1-year mortality in elderly patients with
      hip fracture?
AB  - BACKGROUND: Hip fractures in the elderly are followed by considerable risk of
      functional decline and mortality. QUESTIONS/PURPOSES: The purposes of this study
      were to (1) explore predictive factors of functional level at discharge, (2)
      evaluate 1-year mortality after hip fracture compared with that of the general
      population, and (3) evaluate the affect of early functional outcome on 1-year
      mortality in patients operated on for hip fractures. METHODS: A total of 228
      consecutive patients (average age, 77.6 +/- 7.4 years) with hip fractures who met
      the inclusion criteria were enrolled in an open, prospective, observational
      cohort study. Functional level at discharge was measured with the motor
      Functional Independence Measure (FIM) score, which is the most widely accepted
      functional assessment measure in use in the rehabilitation community. Mortality
      rates in the study population were calculated in absolute numbers and as the
      standardized mortality ratio. Multivariate regression analysis was used to
      explore predictive factors for motor FIM score at discharge and for 1-year
      mortality adjusted for important baseline variables. RESULTS: Age, health status,
      cognitive level, preinjury functional level, and pressure sores after hip
      fracture surgery were independently related to lower discharge motor FIM scores.
      At 1-year followup, 57 patients (25%; 43 women and 14 men) had died. The 1-year
      hip fracture mortality rate compared with that of the general population was 31%
      in our population versus 7% for men and 23% in our population versus 5% for women
      65 years or older. The 1-year standardized mortality rate was 341.3 (95% CI,
      162.5-520.1) for men and 301.6 (95% CI, 212.4-391.8) for women, respectively. The
      all-cause mortality rate observed in this group was higher in all age groups and
      in both sexes when compared with the all-cause age-adjusted mortality of the
      general population. Motor FIM score at discharge was the only independent
      predictor of 1-year mortality after hip fracture. CONCLUSIONS: Functional level
      at discharge is the main determinant of long-term mortality in patients with hip
      fracture. Motor FIM score at discharge is a reliable predictor of mortality and
      can be recommended for clinical use.

PMID- 23546851
TI  - Supratentorial extraventricular anaplastic ependymoma in an adult with repeated
      intratumoral hemorrhage.
AB  - We report the case of a 61-year-old man with supratentorial extraventricular
      anaplastic ependymoma who presented with repeated intratumoral hemorrhage. The
      patient was admitted with headache. Computed tomography and magnetic resonance
      imaging showed an enhancing mass with intratumoral hemorrhage in the right
      temporal lobe. Gross total resection was performed. The tumor was well demarcated
      from the brain tissue, and showed no continuity with the ventricular system.
      Histopathological examination revealed the features of anaplastic ependymoma.
      Therefore, additional radiation therapy and adjuvant chemotherapy were
      administered. Ten months later, the tumor recurred with hemorrhage in the spinal
      canal. This case showed rapid malignant progression and repeated intratumoral
      hemorrhage within a short period of time, both of which are characteristics of
      anaplastic ependymomas. Close observation of the central nervous system and
      adjuvant radiotherapy are mandatory, even if the ependymoma presents with
      repeated intratumoral hemorrhage. 

PMID- 23546852
TI  - Acute oral toxicity and liver oxidant/antioxidant stress of halogenated benzene,
      phenol, and diphenyl ether in mice: a comparative and mechanism exploration.
AB  - The lethal doses (LD50s) of fluorinated, chlorinated, brominated, and iodinated
      benzene, phenol, and diphenyl ether in mice were ascertained respectively under
      the consistent condition. The acute toxicity of four benzenes orders in
      fluorobenzene (FB) < iodobenzene < chlorobenzene~bromobenzene, that of four
      phenols orders in 4-iodophenol~4-bromophenol < 4-chlorophenol (4-MCP) < 4
      fluorophenol (4-MFP), and that of four diphenyl ethers orders in 4,4'
      iododiphenyl ether < 4,4'-difluorodiphenyl ether < 4,4'-dichlorodiphenyl
      ether~4,4'-dibromodiphenyl ether. General behavior adverse effects were observed,
      and poisoned mouse were dissected to observe visceral lesions. FB, 4-MCP, and 4
      MFP produced toxic faster than other halogenated benzenes and phenols, as they
      had lower octanol-water partition coefficients. Pathological changes in liver and
      liver/kidney weight changes were also observed. Hepatic superoxide dismutase,
      catalase activities, and malondialdehyde level were tested after a 28-day
      exposure, which reflects a toxicity order basically consistent with that
      reflected by the LD50s. By theoretical calculation and building models, the
      toxicity of benzene, phenol, and diphenyl ether were influenced by different
      structural properties. 

PMID- 23546853
TI  - Development and implementation of surface water quality standards for protection
      of human health in Korea.
AB  - Current water quality standards for the protection of human health in Korea
      include 17 substances found in rivers and streams. Due to increasing concern over
      the release of hazardous chemicals into the aquatic environment, there has been a
      demand for additional water quality standards. Therefore, the Korean Ministry of
      the Environment plans to gradually increase the number of water quality standards
      to 30 substances, including 22 substances for protection of human health and 8
      substances for protection of aquatic ecosystems by 2015. In this study, new water
      quality standards for protection of human health were established for 1,4
      dioxane, formaldehyde, and hexachlorobenzene. We selected candidate hazardous
      chemicals, conducted a human health risk assessment to determine priority
      chemicals, established water quality standards based on technical analyses and
      comparison with domestic and developed countries' water quality standards, and
      conducted an expert review. Water quality standards for protection of aquatic
      ecosystems will be derived in the near future. This study describes how the water
      quality standards for protection of human health were developed and implemented.
      Current status, recent expansion, and future plans for water quality standards in
      Korea are also covered. 

PMID- 23546854
TI  - Influence of exogenous urea on photosynthetic pigments, (14)CO 2 uptake, and
      urease activity in Elodea densa-environmental implications.
AB  - This paper analyzes the effect of exogenous urea in increased concentration
      gradient (0, 100, 500 and 1,000 mg L(-1)) on photosynthetic pigments (measured
      spectrophotometrically), uptake of (14)CO2 (using radioisotope), and urease
      activity (by measuring ammonia with Nessler's reagent) in leaves of Elodea densa
      Planch. We have observed that low concentration of urea (100 mg L(-1)) stimulates
      the accumulation of photosynthetic pigments and intensifies photosynthesis in E.
      densa, whereas high concentration (1,000 mg L(-1)) suppresses these processes.
      Urease activity increased by approximately 2.7 and 8 fold when exogenous urea
      concentrations were 100 and 500 mg L(-1), respectively. However, exogenous urea
      in high concentration (1,000 mg L(-1)) decreased urease activity by 1.5 fold
      compared to the control. The necessity of mitigating urea and other nitrogen
      containing compounds (NH3 from urea) in water bodies has been discussed with
      emphasis on the potential for phytoremediation of urea using common water weed
      viz. E. densa. 

PMID- 23546855
TI  - Performance evaluation of various stormwater best management practices.
AB  - Many best management practices have been developed and implemented to treat the
      nonpoint source pollution of the aquatic environment in Korea's four major river
      basins. The performance and cost of these facilities were evaluated and compared
      using broad categories, including grassed swales, constructed wetlands, vegetated
      filter strips, hydrodynamic separators, media filters, and infiltration trenches,
      based on the monitoring and maintenance work undertaken between 2005 and 2012.
      Constructed wetlands, media filters, and infiltration trenches generally
      performed better in removing pollutants than other types of facilities, while
      media filters were the most expensive factor in terms of construction and
      operational costs. In addition, constructed wetlands incurred the least
      operational cost, as well as helping to control the quantity of runoff. This
      illustrates that a high cost facility does not necessarily give a better
      performance. A slightly more expensive facility, such as wetland, could prove to
      be a reasonably effective treatment. The selection of the most appropriate
      treatment for stormwater runoff should be based on an overall analysis of
      performance and cost. 

PMID- 23546856
TI  - Development of aquatic life criteria in China: viewpoint on the challenge.
AB  - While more developed countries have a well-established systems to develop water
      quality criteria (WQC), little research has been done on the adequacy of the
      current WQC to protect endemic species of China. In order to maintain the health
      of aquatic ecosystems in China, a series of projects to establish national WQC
      based on regional characteristics has recently been initiated. However, the
      establishment of a completely novel methodology would be costly and time
      consuming. Also, due to the similarities in physiologies and natural histories of
      classes of aquatic organisms, there is no reason to believe that WQC would not be
      sufficient to protect unique species in China. This review was undertaken to
      identify key outstanding issues regarding establishment of aquatic life criteria
      (ALC) to be applied in China, including prioritization of chemicals, test
      species, mode of action, field/semi-field data, and methods of aggregating the
      information and calculating the ALC. This was used to identify the principle
      issues that need to be addressed in order to better understand the methods for
      development of criteria for the protection of aquatic life and provide a
      reference to China and other developing countries committed to the establishment
      of their own WQC system. 

PMID- 23546857
TI  - Assessing heavy metal pollution in the surface soils of a region that had
      undergone three decades of intense industrialization and urbanization.
AB  - Heavy metals in the surface soils from lands of six different use types in one of
      the world's most densely populated regions, which is also a major global
      manufacturing base, were analyzed to assess the impact of urbanization and
      industrialization on soil pollution. A total of 227 surface soil samples were
      collected and analyzed for major heavy metals (As, Cd, Co, Cr, Cu, Fe, Hg, Mn,
      Ni, Pb, and Zn) by using microwave-assisted acid digestion and inductively
      coupled plasma-mass spectrometry (ICP-MS). Multivariate analysis combined with
      enrichment factors showed that surface soils from the region (>7.2 * 10(4) km(2))
      had mean Cd, Cu, Zn, and As concentrations that were over two times higher than
      the background values, with Cd, Cu, and Zn clearly contributed by anthropogenic
      sources. Soil pollution by Pb was more widespread than the other heavy metals,
      which was contributed mostly by anthropogenic sources. The results also indicate
      that Mn, Co, Fe, Cr, and Ni in the surface soils were primarily derived from
      lithogenic sources, while Hg and As contents in the surface soils were controlled
      by both natural and anthropogenic sources. The pollution level and potential
      ecological risk of the surface soils both decreased in the order of: urban areas
      > waste disposal/treatment sites ~ industrial areas > agricultural lands ~ forest
      lands > water source protection areas. These results indicate the significant
      need for the development of pollution prevention and reduction strategies to
      reduce heavy metal pollution for regions undergoing fast industrialization and
      urbanization. 

PMID- 23546858
TI  - The ruptured Achilles tendon: a current overview from biology of rupture to
      treatment.
AB  - The Achilles tendon (AT) is the most frequently ruptured tendon in the human body
      yet the aetiology remains poorly understood. Despite the extensively published
      literature, controversy still surrounds the optimum treatment of complete
      rupture. Both non-operative management and percutaneous repair are attractive
      alternatives to open surgery, which carries the highest complication and cost
      profile. However, the lack of a universally accepted scoring system has limited
      any evaluation of treatment options. A typical UK district general hospital
      treats approximately 3 cases of AT rupture a month. It is therefore important for
      orthopaedic surgeons to correctly diagnose and treat these injuries with respect
      to the best current evidence-based practice. In this review article, we discuss
      the relevant pathophysiology and diagnosis of the ruptured AT and summarize the
      current evidence for treatment.

PMID- 23546859
TI  - Paracoccus siganidrum sp. nov., isolated from fish gastrointestinal tract.
AB  - A bacterial strain, designated M26(T), was isolated from a fish gastrointestinal
      tract, collected from Zhanjiang Port, South China. 16S rRNA gene sequence
      analysis indicated that strain M26(T) belongs to the subclass alpha
      Proteobacteria, being related to the genus Paracoccus, and sharing highest
      sequence similarity with Paracoccus alcaliphilus JCM 7364(T) (98.1 %), Paracoccus
      huijuniae FLN-7(T) (97.3 %), Paracoccus stylophorae KTW-16(T) (97.1 %) and
      Paracoccus seriniphilus DSM 14827(T) (96.9 %). The major quinone was determined
      to be ubiquinone Q-10, with Q-9 and Q-8 as minor components. The major fatty acid
      was identified as C18:1omega7c, with smaller amounts of C18:0 and C16:0. The G+C
      content of the genomic DNA was determined to be 64.3 mol%. The DNA hybridization
      value between strain M26(T) and the most closely related type strain, P.
      alcaliphilus, was 29.0 +/- 1.0 %. The results of physiological and biochemical
      tests and low DNA-DNA relatedness showed that the strain could be readily
      distinguished from closely related species. On the basis of these phenotypic and
      genotypic data, strain M26(T) is concluded to represent a novel species of the
      genus Paracoccus, for which the name Paracoccus siganidrum sp. nov. is proposed.
      The type strain is M26(T) (=CCTCC AB 2012865(T) = DSM 26381(T)).

PMID- 23546861
TI  - Tractography demonstrates dentate-rubro-thalamic tract disruption in an adult
      with cerebellar mutism.
AB  - A 55-year-old female is presented with transient cerebellar mutism caused by a
      well-circumscribed left pontine infarction due to postoperative basilar
      perforator occlusion. Although conventional T2 imaging shows a well-demarcated
      lesion confined to the pontine region, diffusion tensor imaging shows an
      asymmetry in fractional anisotropy in the superior cerebellar peduncle. This
      supports the general hypothesis that cerebellar mutism is caused by functional
      disruption of the dentate-rubro-thalamic tract. Correlating postoperative
      anatomic changes to a heterogenic clinical syndrome remains challenging, however.

PMID- 23546862
TI  - Fifteen-year experience in managing obturator hernia: from open to laparoscopic
      approach.
AB  - PURPOSE: Obturator hernia is a rare disease and preoperative diagnosis is always
      difficult. There are increasing reports employing laparoscopic approach in the
      recent literature. Our aim was to review and compare the open and laparoscopic
      approach in repairing obturator hernia. METHODS: All patients with obturator
      hernia from 1997 to 2011 were recruited. Patient's demographics, presentation,
      operative details, morbidity, and mortality were retrospectively collected and
      reviewed. RESULTS: There were 36 patients during the 15-year period. All of them
      were elderly ladies (median 83). Nineteen underwent open surgery while 16
      received laparoscopic surgery. Both age and ASA were comparable. The median
      operative time was 68 and 65 min for laparoscopic and open group, respectively (p
      = 0.690). The median hospital stay was significantly longer in the open group (19
      vs 5 days, p = 0.007). There were less major complications (p = 0.004) and
      mortality (p = 0.049) in the laparoscopic group. Two recurrences were reported in
      the laparoscopic group, although statistically not significant (p = 0.202).
      CONCLUSIONS: Laparoscopic repair can achieve a shorter hospital stay and has
      lesser major complications and mortality in selected patients.

PMID- 23546863
TI  - Hernia sac of indirect inguinal hernia: invagination, excision, or ligation?
AB  - This study compares the effect of invaginating excision of hernia sac without
      ligation with the traditional method of high ligation of the hernia sac on
      postoperative pain and recurrence. PATIENTS AND METHODS: This multicenter
      prospective randomized study included 152 patients with 167 primary indirect
      inguinal hernias. In group I (54 hernias), the sac was not opened and was
      inverted with the finger into the peritoneal cavity. In group E (56 hernias), the
      sac was excised at the neck without ligation. In group L (57 hernias), the sac
      was transfixed at the neck and excised in the traditional manner. The repair of
      the posterior wall of the inguinal canal was done according to Lichtenstein
      tension-free technique. Mean length of follow-up was 81.50 +/- 22.34, 79.35 +/-
      26.76, and 77.83 +/- 21.26 months, respectively. RESULTS: Postoperative seroma
      occurred in 1 patient (0.60%) in group E and 1 patient (0.60%) in group L.
      Surgical site infection occurred in 2 patients (1.20%) in group I, 1 patient
      (0.60%) in group E, and 2 patients (1.20%) in group L. Mean postoperative pain
      score was 3.04 +/- 2.11, 3.98 +/- 2.33 and 4.06 +/- 2.43, respectively (p:
      0.049). Chronic pain occurred in 3 patients in group I (1.80%), 3 patients in
      group E (1.80%), and 5 patients in group L (3.00%) (p: 0.749). The difference
      between the complications in three groups was statistically insignificant (p:
      0.887). Hernia recurrence occurred in 3 patients (1.80%) in group I, 1 patient
      (0.60%) in group E, and 1 patient (0.60%) in group L (p: 0.429). CONCLUSION:
      Invagination and excision of the hernia sac do not have adverse effects on repair
      integrity. They limit the dissection and reduce the morbidity and risk of injury
      to the spermatic cord and surrounded structures. They are safer and more
      appropriate for repair of sliding hernia. Ligation of the hernia sac in inguinal
      hernia surgery is not only unnecessary and time consuming but also leads to
      increased postoperative pain. Recurrence rates are statistically unaffected by
      not ligating the sac.

PMID- 23546864
TI  - Randomized clinical trial of mesh fixation with "double crown" versus "sutures
      and tackers" in laparoscopic ventral hernia repair.
AB  - BACKGROUND: Although laparoscopic intra-peritoneal mesh repair (LVHR) is a well
      established treatment option to repair ventral and incisional hernias, no
      consensus in the literature can be found on the best method of fixation of the
      mesh to the abdominal wall. METHODS: Between December 2004 and July 2008, 76
      patients undergoing a LVHR were randomized between mesh fixation using a double
      row of spiral tackers (DC) (n = 33) and mesh fixation with transfascial sutures
      combined with one row of spiral tackers (S&T) (n = 43), in the WoW trial (with or
      without sutures). Patients were clinically examined and evaluated using a visual
      analog scale for pain (VAS) in rest and after coughing 4 h post-operatively,
      after 4 weeks and 3 months after surgery. Primary endpoint of the study was
      abdominal wall pain, defined as a VAS score of at least 1.0 cm, at 3 months post
      operative. Quality of life was quantified with the SF-36 questionnaire
      preoperatively and after 3 months. Secondary endpoint was the recurrence rate at
      24-month follow-up. RESULTS: The DC and S&T group were comparable in age, gender,
      ASA score, BMI, indication, hernia, and mesh variables. The DC group had a
      significant shorter operating time compared with the S&T group (74 vs 96 min; p =
      0.014) and a significant lower mean VAS score 4 h post-operatively (in rest; p =
      0.028/coughing; p = 0.013). At 3 months, there were significant more patients in
      the S&T group with VAS score >=1.0 cm (31.4 vs 8.3 %; p = 0.036). Clinical follow
      up at 24 months was obtained in 63 patients (82.9 %). The recurrence rate at 24
      months was 7.9 % overall (5/63). There were more recurrences in the S&T group
      (4/36) than in the DC group (1/27), but this difference was not significant (11.1
      vs 3.7 %; p = 0.381). CONCLUSION: We found that double-crown fixation of intra
      peritoneal mesh during laparoscopic ventral hernia repair was quicker, was less
      painful immediately post-operative and after 3 months, and did not increase the
      recurrence rate at 24 months. In hernias at a distance from the bony borders of
      the abdomen, transfascial sutures can be omitted if a double crown of tackers is
      placed.

PMID- 23546865
TI  - PORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro
      inflammatory cytokines via TLR2 activation in THP-1 cells.
AB  - Infection with Chlamydia trachomatis induces inflammatory pathologies in the
      urogenital tract that can lead to infertility and ectopic pregnancy. Pathogenesis
      of infection has been mostly attributed to excessive cytokine production.
      However, precise mechanisms on how C. trachomatis triggers this production, and
      which protein(s) stimulate inflammatory cytokines remains unknown. In the present
      study, the C. trachomatis pORF5 protein induced tumor necrosis factor alpha (TNF
      alpha), interleukin-1 beta (IL-1beta) and interleukin-8 (IL-8) in dose- and time
      dependent manners in the THP-1 human monocyte cell line. We found that
      intracellular p38/mitogen-activated protein kinase (MAPK) and extracellular
      signal-regulated kinase (ERK)/MAPK signaling pathways were required for the
      induction of TNF-alpha, IL-1beta and IL-8. Blockade of toll-like receptor 2
      (TLR2) signaling reduced induction levels of TNF-alpha, IL-8 and IL-1beta. We
      concluded that the C. trachomatis pORF5 protein might contribute to the
      inflammatory processes associated with chlamydial infections.

PMID- 23546866
TI  - Reactive oxygen species-mediated activation of the Akt/ASK1/p38 signaling cascade
      and p21(Cip1) downregulation are required for shikonin-induced apoptosis.
AB  - Shikonin derivatives exert powerful cytotoxic effects, induce apoptosis and
      escape multidrug resistance in cancer. However, the diverse mechanisms underlying
      their anticancer activities are not completely understood. Here, we demonstrated
      that shikonin-induced apoptosis is caused by reactive oxygen species (ROS)
      mediated activation of Akt/ASK1/p38 mitogen-activated protein kinase (MAPK) and
      downregulation of p21(Cip1). In the presence of shikonin, inactivation of Akt
      caused apoptosis signal-regulating kinase 1 (ASK1) dephosphorylation at Ser83,
      which is associated with ASK1 activation. Shikonin-induced apoptosis was enhanced
      by inhibition of Akt, whereas overexpression of constitutively active Akt
      prevented apoptosis through modulating ASK1 phosphorylation. Silencing ASK1 and
      MKK3/6 by siRNA reduced the activation of MAPK kinases (MKK) 3/6 and p38 MAPK,
      and apoptosis, respectively. Antioxidant N-acetyl cysteine attenuated ASK1
      dephosphorylation and p38 MAPK activation, indicating that shikonin-induced ROS
      is involved in the activation of Akt/ASK1/p38 pathway. Expression of p21(Cip1)
      was significantly induced in early response, but gradually decreased by prolonged
      exposure to shikonin. Overexpression of p21(Cip1) have kept cells longer in G1
      phase and attenuated shikonin-induced apoptosis. Depletion of p21(Cip1)
      facilitated shikonin-induced apoptosis, implying that p21(Cip1) delayed shikonin
      induced apoptosis via G1 arrest. Immunohistochemistry and in vitro binding assays
      showed transiently altered localization of p21(Cip1) to the cytoplasm by
      shikonin, which was blocked by Akt inhibition. The cytoplasmic p21(Cip1) actually
      binds to and inhibits the activity of ASK1, regulating the cell cycle progression
      at G1. These findings suggest that shikonin-induced ROS activated ASK1 by
      decreasing Ser83 phosphorylation and by dissociation of the negative regulator
      p21(Cip1), leading to p38 MAPK activation, and finally, promoting apoptosis.

PMID- 23546867
TI  - Ionizing radiation-inducible microRNA miR-193a-3p induces apoptosis by directly
      targeting Mcl-1.
AB  - The functions of microRNAs (miRNAs) as either oncogenes or tumor suppressors in
      regulating cancer-related events have been established. We analyzed the
      alterations in the miRNA expression profile of the glioma cell line U-251 caused
      by ionizing radiation (IR) by using an miRNA array and identified several miRNAs
      whose expression was significantly affected by IR. Among the IR-responsive
      miRNAs, we further examined the function of miR-193a-3p, which exhibited the most
      significant growth-inhibiting effect. miR-193a-3p was observed to induce
      apoptosis in both U-251 and HeLa cells. We also demonstrated that miR-193a-3p
      induces the accumulation of intracellular reactive oxygen species (ROS) and DNA
      damage as determined by the level of gammaH2AX and by performing the comet assay.
      The induction of both apoptosis and DNA damage by miR-193a-3p was blocked by
      antioxidant treatment, indicating the crucial role of ROS in the action of miR
      193a-3p. Among the putative target proteins, the expression of Mcl-1, an anti
      apoptotic Bcl-2 family member, decreased because of miR-193a-3p transfection. A
      reporter assay using a luciferase construct containing the 3'-untranslated region
      of Mcl-1 confirmed that Mcl-1 is a direct target of miR-193a-3p. Down-regulation
      of Mcl-1 by siRNA transfection closely mimicked the outcome of miR-193a-3p
      transfection showing increased ROS, DNA damage, cytochrome c release, and
      apoptosis. Ectopic expression of Mcl-1 suppressed the pro-apoptotic action of miR
      193a-3p, suggesting that Mcl-1 depletion is critical for miR-193a-3p induced
      apoptosis. Collectively, our results suggest a novel function for miR-193a-3p and
      its potential application in cancer therapy.

PMID- 23546868
TI  - Process characterization of hCTLA4Ig production in transgenic rice cell cultures
      using a 3-L bioreactor.
AB  - Most of the technical know-how and experience of bioreactor engineering is
      applicable to plant cell cultures. In this study, transgenic rice cell cultures
      using RAmy3D promoter were used for the production of human cytotoxic T
      lymphocyte antigen 4-immunoglobulin (hCTLA4Ig). In process aspect, the rice cells
      during production phase are strongly influenced by hydrodynamic stresses, such as
      shear stress and bubble burst. Therefore, the effects of agitation and aeration
      rates on cell growth and hCTLA4Ig production were investigated in a 3-L multi
      bioreactor. By increasing over 240 rpm, the detrimental effects on cell growth
      and hCTLA4Ig production were observed. At an aeration rate of 0.3 vvm, relative
      cell viability sharply decreased 2 days earlier than those of lower aeration
      rates. In addition, it was confirmed that the specific yields and the specific
      productivity at 0.3 vvm were superior to those values at 0.05 vvm. Overall,
      higher aeration rate showed the improved hCTLA4Ig production in combination
      experiment. High aeration rates in general, however, have an undesired effect as
      excessive aeration was found to negatively affect the quality of hCTLA4Ig.
      Consequently, the hydrodynamic conditions must be tightly regulated during
      bioreactor operation in order to enhance hCTLA4Ig productivity and quality in
      transgenic rice cell cultures.

PMID- 23546870
TI  - Role of Met93 and Thr96 in the lid hinge region of Rhizopus chinensis lipase.
AB  - We engineered Rhizopus chinensis lipase to study its critical amino acid role in
      catalytic properties. Based on the amino acid sequence and three-dimensional
      model of the lipase, residues located in its lid hinge region (Met93 and Thr96)
      were replaced with corresponding amino acid residues (Ile93 and Asn96) found in
      the lid hinge region of Rhizopus oryzae lipase. The substitutions in the lid
      hinge region affected not only substrate specificity but also the thermostability
      of the lipase. Both lipases preferred p-nitrophenyl laurate and glyceryl
      trilaurate (C12). However, the variant S4-3O showed a slight decline in activity
      toward long-chain fatty acid (C16-C18). When enzymes activities decreased by
      half, the temperature of the variant (45  degrees C) was 22  degrees C lower than
      the parent (67  degrees C), probably substantially destabilized the structure of
      the lid region. The interfacial kinetic analysis of S4-3O suggested that the
      lower catalytic efficiency was due to a higher K m* value. According to the
      lipase structure investigated, Ile93Met played a role of narrowing the size of
      the hydrophobic patch, which affected the substrate binding affinity, and
      Asn96Thr destabilized the structure of the lipase by disrupting the H-bond
      interaction in the lid region.

PMID- 23546869
TI  - Comparison of Yarrowia lipolytica and Pichia pastoris cellular response to
      different agents of oxidative stress.
AB  - Yeast cells exposed to adverse conditions employ a number of defense mechanisms
      in order to respond effectively to the stress effects of reactive oxygen species.
      In this work, the cellular response of Yarrowia lipolytica and Pichia pastoris to
      the exposure to the ROS-inducing agents' paraquat, hydrogen peroxide, and
      increased air pressure was analyzed. Yeast cells at exponential phase were
      exposed for 3 h to 1 mM paraquat, to 50 mM H2O2, or to increased air pressure of
      3 or 5 bar. For both strains, the cellular viability loss and lipid peroxidation
      was lower for the cells exposed to increased air pressure than for those exposed
      to chemical oxidants. The glutathione induction occurred only in Y. lipolytica
      strain and reached the highest level as a response to PQ exposure. In general,
      antioxidant enzymes were more expressed in Y. lipolytica than in P. pastoris. The
      enzyme superoxide dismutase was induced in both strains under all the oxidant
      conditions but was dependent on the cellular growth phase, being undetectable in
      non-growing cells, whereas glutathione reductase was more induced in those
      conditions. Hydrogen peroxide was the most efficient inducer of catalase. Both
      yeast cultures underwent no cellular growth inhibition with increased air
      pressure, indicating that these yeast species were able to adapt to the oxidative
      stressful environment.

PMID- 23546871
TI  - In vitro culture, determination, and directed differentiation of adult adipose
      derived stem cells towards cardiomyocyte-like cells induced by angiotensin II.
AB  - The in vitro basic biological characteristics and directed differentiation
      potential towards cardiomyocytes of adult adipose-derived stem cells (ADSCs)
      induced by angiotensin II were both investigated. ADSCs were isolated from adult
      adipose tissue and cultured in vitro, and were subsequently induced into
      adipocytes, chondrocytes, and osteoblasts for assays of multipotential
      differentiation. The morphological characteristics of ADSCs were observed under
      an inverted microscope in bright field and phase-contrast ways and a confocal
      laser scanning microscopy. Moreover, the directional differentiation potential
      was observed by Oil Red, alkaline phosphatase, von Kossa, and toluidine blue
      stainings, respectively. The expressions of CD34, CD44, CD45, CD105, and HLA-DR
      were also detected via flow cytometry. Following to this, ADSCs were induced by
      angiotensin II and basic fibroblast growth factor for the purpose of directional
      differentiation towards cardiomyocyte-like cells, and the cells treated with 5
      azacytidine were regarded as the control. The results showed that the isolated
      and cultured ADSCs presented a typical morphology of fusiform shape and also
      expressed CD44, CD105, but not CD34, CD45, and HLA-DR with assays of flow
      cytometry. The multi-differentiations to adipocytes, chondrocytes, and
      osteoblasts confirmed that the isolated cells maintained the stem characteristics
      generating from adipose tissues. After 4 weeks of induction by angiotensin II,
      the cells expressed myosin heavy chain, troponin I, and connexin43 by
      immunocytochemistry staining, but without beating of the cells. This current
      study indicated that ADSCs possessed the characteristics of mesenchymal stem
      cells and angiotensin II could induce ADSCs into cardiomyocyte-like cells.

PMID- 23546873
TI  - Analysis of 11 trials comparing muscle-sparing with posterolateral thoracotomy.
AB  - BACKGROUND: Muscle-sparing thoracotomy (MST) has recently been developed in an
      attempt to minimize tissue injuries during thoracic operation and postoperative
      sequelae. However, its potential advantages over traditional posterolateral
      thoracotomy (PLT) remain to be determined. Here, we performed a meta-analysis on
      all available studies that compare the pros and cons between the two approaches.
      METHODS: A total of 11 relevant studies were found to satisfy our inclusive
      criteria from three electronic databases. End points included postoperative pain,
      pulmonary function, postoperative mortality, and perioperative complications.
      RESULTS: Data from seven randomized controlled trials and four observational
      studies were included (n = 408 and 564, respectively). Compared with PLT group,
      MST group had a significantly reduced postoperative visual analog scale score on
      day 1 (weighted mean difference [WMD], -0.79; 95% confidence interval [CI], -1.10
      to -0.48), week 1 (WMD, -0.60; 95% CI, -0.98 to -0.22), and month 1 (WMD, -0.73;
      95% CI, -1.30 to -0.16). However, no difference between the two approaches was
      found on postoperative forced vital capacity and forced expiratory volume in 1
      second (week 1: standardized mean difference [SMD], 0.44; 95% CI, -0.18 to 1.07
      versus SMD, 0.53; 95% CI, -0.13 to 1.18; month 1: SMD 0.26; 95% CI, -0.26 to 0.78
      versus SMD, 0.38; 95% CI, -0.25 to 1.00), mortality (odds ratio [OR], 1.23; 95%
      CI, 0.49 to 3.09), and complications (OR, 0.86; 95% CI, 0.60 to 1.23).
      CONCLUSIONS: MST may improve postoperative pain, but shows less effect on other
      perioperative parameters.

PMID- 23546874
TI  - Comparison of the total length and areas of upper central incisors between males
      and females using computer-assisted morphometry.
AB  - The determination of measurements of teeth facilitates various procedures in
      dentistry. The purpose of this study was to evaluate the total length and the
      area of the non-extracted upper central incisors (UCI). Periapical radiographies
      of 42 UCI were placed over a lighted box. The outlines of the teeth and the pulp
      cavity were traced onto sheets and then measured using an image analyzer. The
      area of the upper left central incisor tooth (tooth 21) was statistically
      significantly larger in males than in females (p = 0.02). The total length of the
      right UCI was similar to that of the left one. This study demonstrates that
      computer-assisted morphometry is an important tool for the evaluation of the
      total length and areas of teeth and their pulp cavities. The significantly larger
      area of tooth 21 in males compared to females has anthropomorphic and clinical
      implications.

PMID- 23546875
TI  - SUMOylation of the farnesoid X receptor (FXR) regulates the expression of FXR
      target genes.
AB  - BACKGROUND: Small ubiquitin-like modifiers (SUMO) are covalently conjugated to
      other proteins including nuclear receptors leading to modification of various
      cellular processes. RESULTS: Ligand-dependent SUMOylation of farnesoid X receptor
      (FXR) negatively regulates the expression of its target genes. CONCLUSION: SUMO
      modification attenuates the capacity of FXR to function as a transcriptional
      activator. SIGNIFICANCE: Defining post-translation modification of FXR bySUMOis
      important to understanding how this nuclear receptor functions in health and
      disease. The farnesoid X receptor (FXR) belongs to a family of ligand-activated
      transcription factors that regulate many aspects of metabolism including bile
      acid homeostasis. Here we show that FXR is covalently modified by the small
      ubiquitin-like modifier (Sumo1), an important regulator of cell signaling and
      transcription. Well conserved consensus sites at lysine 122 and 275 in the AF-1
      and ligand binding domains, respectively, of FXR were subject to SUMOylation in
      vitro and in vivo. Chromatin immunoprecipitation (ChIP) analysis showed that
      Sumo1 was recruited to the bile salt export pump (BSEP), the small heterodimer
      partner (SHP), and the OSTalpha-OSTbeta organic solute transporter loci in a
      ligand-dependent fashion. Sequential chromatin immunoprecipitation (ChIP-ReChIP)
      verified the concurrent binding of FXR and Sumo1 to the BSEP and SHP promoters.
      Overexpression of Sumo1 markedly decreased binding and/or recruitment of FXR to
      the BSEP and SHP promoters on ChIP-ReChIP. SUMOylation did not have an apparent
      effect on nuclear localization of FXR. Expression of Sumo1 markedly inhibited the
      ligand-dependent, transactivation of BSEP and SHP promoters by FXR/retinoid X
      receptor alpha (RXRalpha) in HepG2 cells. In contrast, mutations that abolished
      SUMOylation of FXR or siRNA knockdown of Sumo1 expression augmented the
      transactivation of BSEP and SHP promoters by FXR. Pathways for SUMOylation were
      significantly altered during obstructive cholestasis with differential Sumo1
      recruitment to the promoters of FXR target genes. In conclusion, FXR is subject
      to SUMOylation that regulates its capacity to transactivate its target genes in
      normal liver and during obstructive cholestasis.

PMID- 23546876
TI  - The structure of Bradyrhizobium japonicum transcription factor FixK2 unveils
      sites of DNA binding and oxidation.
AB  - FixK2 is a regulatory protein that activates a large number of genes for the
      anoxic and microoxic, endosymbiotic, and nitrogen-fixing life styles of the alpha
      proteobacterium Bradyrhizobium japonicum. FixK2 belongs to the cAMP receptor
      protein (CRP) superfamily. Although most CRP family members are coregulated by
      effector molecules, the activity of FixK2 is negatively controlled by oxidation
      of its single cysteine (Cys-183) located next to the DNA-binding domain and
      possibly also by proteolysis. Here, we report the three-dimensional x-ray
      structure of FixK2, a representative of the FixK subgroup of the CRP superfamily.
      Crystallization succeeded only when (i) an oxidation- and protease-insensitive
      protein variant (FixK2(C183S)-His6) was used in which Cys-183 was replaced with
      serine and the C terminus was fused with a hexahistidine tag and (ii) this
      protein was allowed to form a complex with a 30-mer double-stranded target DNA.
      The structure of the FixK2-DNA complex was solved at a resolution of 1.77 A, at
      which the protein formed a homodimer. The precise protein-DNA contacts were
      identified, which led to an affirmation of the canonical target sequence, the so
      called FixK2 box. The C terminus is surface-exposed, which might explain its
      sensitivity to specific cleavage and degradation. The oxidation-sensitive Cys-183
      is also surface-exposed and in close proximity to DNA. Therefore, we propose a
      mechanism whereby the oxo acids generated after oxidation of the cysteine thiol
      cause an electrostatic repulsion, thus preventing specific DNA binding.

PMID- 23546877
TI  - The molecular basis of K+ exclusion by the Escherichia coli ammonium channel
      AmtB.
AB  - Members of the Amt family of channels mediate the transport of ammonium. The form
      of ammonium, NH3 or NH4(+), carried by these proteins remains controversial, and
      the mechanism by which they select against K(+) ions is unclear. We describe here
      a set of Escherichia coli AmtB proteins carrying mutations at the conserved twin
      histidine site within the conduction pore that have altered substrate specificity
      and now transport K(+). Subsequent work established that AmtB-mediated K(+)
      uptake occurred against a concentration gradient and was membrane potential
      dependent. These findings indicate that the twin-histidine element serves as a
      filter to prevent K(+) conduction and strongly support the notion that Amt
      proteins transport cations (NH4(+) or, in mutant proteins, K(+)) rather than NH3
      gas molecules through their conduction pores.

PMID- 23546878
TI  - Nitric oxide modifies global histone methylation by inhibiting Jumonji C domain
      containing demethylases.
AB  - Methylation of lysine residues on histone tails is an important epigenetic
      modification that is dynamically regulated through the combined effects of
      methyltransferases and demethylases. The Jumonji C domain Fe(II) alpha
      ketoglutarate family of proteins performs the majority of histone demethylation.
      We demonstrate that nitric oxide ((*)NO) directly inhibits the activity of the
      demethylase KDM3A by forming a nitrosyliron complex in the catalytic pocket.
      Exposing cells to either chemical or cellular sources of (*)NO resulted in a
      significant increase in dimethyl Lys-9 on histone 3 (H3K9me2), the preferred
      substrate for KDM3A. G9a, the primary methyltransferase acting on H3K9me2, was
      down-regulated in response to (*)NO, and changes in methylation state could not
      be accounted for by methylation in general. Furthermore, cellular iron
      sequestration via dinitrosyliron complex formation correlated with increased
      methylation. The mRNA of several histone demethylases and methyltransferases was
      also differentially regulated in response to (*)NO. Taken together, these data
      reveal three novel and distinct mechanisms whereby (*)NO can affect histone
      methylation as follows: direct inhibition of Jumonji C demethylase activity,
      reduction in iron cofactor availability, and regulation of expression of methyl
      modifying enzymes. This model of (*)NO as an epigenetic modulator provides a
      novel explanation for nonclassical gene regulation by (*)NO.

PMID- 23546879
TI  - Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the
      Porphyromonas gingivalis secreted cysteine protease (RgpB).
AB  - The colonic epithelial surface is protected by an inner mucus layer that the
      commensal microflora cannot penetrate. We previously demonstrated that Entamoeba
      histolytica secretes a protease capable of dissolving this layer that is required
      for parasite penetration. Here, we asked whether there are bacteria that can
      secrete similar proteases. We screened bacterial culture supernatants for such
      activity using recombinant fragments of the MUC2 mucin, the major structural
      component, and the only gel-forming mucin in the colonic mucus. MUC2 has two
      central heavily O-glycosylated mucin domains that are protease-resistant and has
      cysteine-rich N and C termini responsible for polymerization. Culture
      supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases
      responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N
      terminal region was unaffected. The active enzyme was isolated and identified as
      Arg-gingipain B (RgpB). Two cleavage sites were localized to IR?TT and NR?QA.
      IR?TT cleavage will disrupt the MUC2 polymers. Because this site has two
      potential O-glycosylation sites, we tested whether recombinant GalNAc
      transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT
      sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT,
      rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3
      was expressed in CHO cells expressing the MUC2 C terminus, the second threonine
      was glycosylated, and the protein became resistant to RgpB cleavage. These
      findings suggest that bacteria can produce proteases capable of dissolving the
      inner protective mucus layer by specific cleavages in the MUC2 mucin and that
      this cleavage can be modulated by site-specific O-glycosylation.

PMID- 23546880
TI  - TGF-beta-activated kinase 1 (Tak1) mediates agonist-induced Smad activation and
      linker region phosphorylation in embryonic craniofacial neural crest-derived
      cells.
AB  - BACKGROUND: The role of Smad-independent TGF-beta signaling in craniofacial
      development is poorly elucidated. RESULTS: In craniofacial mesenchymal cells,
      Tak1 regulates both R-Smad C-terminal and linker region phosphorylation in TGF
      beta signaling. CONCLUSION: Tak1 plays an irreplaceable role in craniofacial ecto
      mesenchyme during embryogenesis. SIGNIFICANCE: Understanding the mechanisms of
      TGF-beta signaling contributes to knowledge of pathogenetic mechanisms underlying
      common craniofacial birth defects. Although the importance of TGF-beta
      superfamily signaling in craniofacial growth and patterning is well established,
      the precise details of its signaling mechanisms are still poorly understood. This
      is in part because of the concentration of studies on the role of the Smad
      dependent (so-called "canonical") signaling pathways relative to the Smad
      independent ones in many biological processes. Here, we have addressed the role
      of TGF-beta-activated kinase 1 (Tak1, Map3k7), one of the key mediators of Smad
      independent (noncanonical) TGF-beta superfamily signaling in craniofacial
      development, by deleting Tak1 specifically in the neural crest lineage. Tak1
      deficient mutants display a round skull, hypoplastic maxilla and mandible, and
      cleft palate resulting from a failure of palatal shelves to appropriately elevate
      and fuse. Our studies show that in neural crest-derived craniofacial ecto
      mesenchymal cells, Tak1 is not only required for TGF-beta- and bone morphogenetic
      protein-induced p38 Mapk activation but also plays a role in agonist-induced C
      terminal and linker region phosphorylation of the receptor-mediated R-Smads.
      Specifically, we demonstrate that the agonist-induced linker region
      phosphorylation of Smad2 at Thr-220, which has been shown to be critical for full
      transcriptional activity of Smad2, is dependent on Tak1 activity and that in
      palatal mesenchymal cells TGFbetaRI and Tak1 kinases mediate both overlapping and
      distinct TGF-beta2-induced transcriptional responses. To summarize, our results
      suggest that in neural crest-derived ecto-mesenchymal cells, Tak1 provides a
      critical point of intersection in a complex dialogue between the canonical and
      noncanonical arms of TGF-beta superfamily signaling required for normal
      craniofacial development.

PMID- 23546881
TI  - Mass spectrometry-based footprinting reveals structural dynamics of loop E of the
      chlorophyll-binding protein CP43 during photosystem II assembly in the
      cyanobacterium Synechocystis 6803.
AB  - The PSII repair cycle is required for sustainable photosynthesis in oxygenic
      photosynthetic organisms. In cyanobacteria and higher plants, proteolysis of the
      precursor D1 protein (pD1) to expose a C-terminal carboxylate group is an
      essential step leading to coordination of the Mn4CaO5 cluster, the site of water
      oxidation. Psb27 appears to associate with both pD1- and D1-containing PSII
      assembly intermediates by closely interacting with CP43. Here, we report that
      reduced binding affinity between CP43 and Psb27 is triggered by the removal of
      the C-terminal extension of the pD1 protein. A mass spectrometry-based
      footprinting strategy was adopted to probe solvent-exposed aspartic and glutamic
      acid residues on the CP43 protein. By comparing the extent of footprinting
      between HT3DeltactpADelta27PSII and HT3DeltactpAPSII, two genetically modified
      PSII assembly complexes, we found that Psb27 binds to CP43 on the side of Loop E
      distal to the pseudo-symmetrical D1-D2 axis. By comparing a second pair of PSII
      assembly complexes, we discovered that Loop E of CP43 undergoes a significant
      conformational rearrangement due to the removal of the pD1 C-terminal extension,
      altering the Psb27-CP43 binding interface. The significance of this
      conformational rearrangement is discussed in the context of recruitment of the
      PSII lumenal extrinsic proteins and Mn4CaO5 cluster assembly. In addition to
      CP43's previously known function as one of the core PSII antenna proteins, this
      work demonstrates that Loop E of CP43 plays an important role in the functional
      assembly of the Water Oxidizing Center (WOC) during PSII biogenesis.

PMID- 23546882
TI  - MicroRNA-144 is regulated by activator protein-1 (AP-1) and decreases expression
      of Alzheimer disease-related a disintegrin and metalloprotease 10 (ADAM10).
AB  - BACKGROUND: MicroRNA (miR) dysregulation is found in Alzheimer disease (AD). A
      disintegrin and metalloprotease 10 (ADAM10) prevents generation of amyloid beta
      (Abeta) and decrease AD pathology. RESULTS: miR-144 suppresses ADAM10 expression
      and is up-regulated by activator protein-1. CONCLUSION: miR-144 is a negative
      regulator of ADAM10 and may be involved in AD pathogenesis. SIGNIFICANCE: The
      first work to demonstrate the function of miRNA-144 and its regulation in the
      pathogenesis of AD. Amyloid beta-peptide (Abeta) accumulating in the brain of
      Alzheimer disease (AD) patients is believed to be the main pathophysiologcal
      cause of the disease. Proteolytic processing of the amyloid precursor protein by
      alpha-secretase ADAM10 (a disintegrin and metalloprotease 10) protects the brain
      from the production of the Abeta. Meanwhile, dysregulation or aberrant expression
      of microRNAs (miRNAs) has been widely documented in AD patients. In this study,
      we demonstrated that overexpression of miR-144, which was previously reported to
      be increased in elderly primate brains and AD patients, significantly decreased
      activity of the luciferase reporter containing the ADAM10 3'-untranslated region
      (3'-UTR) and suppressed the ADAM10 protein level, whereas the miR-144 inhibitor
      led to an increase of the luciferase activity. The negative regulation caused by
      miR-144 was strictly dependent on the binding of the miRNA to its recognition
      element in the ADAM10 3'-UTR. Moreover, we also showed that activator protein-1
      regulates the transcription of miR-144 and the up-regulation of miR-144 at least
      partially induces the suppression of the ADAM10 protein in the presence of Abeta.
      In addition, we found that miR-451, a miRNA processed from a single gene locus
      with miR-144, is also involved in the regulation of ADAM10 expression. Taken
      together, our data therefore demonstrate miR-144/451 is a negative regulator of
      the ADAM10 protein and suggest a mechanistic role for miR-144/451 in AD
      pathogenesis.

PMID- 23546883
TI  - The Brucella abortus general stress response system regulates chronic mammalian
      infection and is controlled by phosphorylation and proteolysis.
AB  - BACKGROUND: Virulence of pathogenic bacteria is often determined by their ability
      to adapt to stress. RESULTS: The Brucella abortus general stress response (GSR)
      system is required for chronic mammalian infection and is regulated by
      phosphorylation and proteolysis. CONCLUSION: The B. abortus GSR signaling pathway
      has multiple layers of post-translational control and is a determinant of chronic
      infection. SIGNIFICANCE: This study provides new, molecular level insight into
      chronic Brucella infection. Brucella spp. are adept at establishing a chronic
      infection in mammals. We demonstrate that core components of the alpha
      proteobacterial general stress response (GSR) system, PhyR and sigma(E1), are
      required for Brucella abortus stress survival in vitro and maintenance of chronic
      murine infection in vivo. DeltaphyR and DeltarpoE1 null mutants exhibit decreased
      survival under acute oxidative and acid stress but are not defective in infection
      of primary murine macrophages or in initial colonization of BALB/c mouse spleens.
      However, DeltaphyR and DeltarpoE1 mutants are attenuated in spleens beginning 1
      month postinfection. Thus, the B. abortus GSR system is dispensable for
      colonization but is required to maintain chronic infection. A genome-scale
      analysis of the B. abortus GSR regulon identified stress response genes
      previously linked to virulence and genes that affect immunomodulatory components
      of the cell envelope. These data support a model in which the GSR system affects
      both stress survival and the interface between B. abortus and the host immune
      system. We further demonstrate that PhyR proteolysis is a unique feature of GSR
      control in B. abortus. Proteolysis of PhyR provides a mechanism to avoid spurious
      PhyR protein interactions that inappropriately activate GSR-dependent
      transcription. We conclude that the B. abortus GSR system regulates acute stress
      adaptation and long term survival within a mammalian host and that PhyR
      proteolysis is a novel regulatory feature in B. abortus that ensures proper
      control of GSR transcription.

PMID- 23546884
TI  - Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone
      (LDN).
AB  - Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome, which
      involves glial activation and central sensitization in the central nervous
      system. Here, we describe positive outcomes of two CRPS patients, after they were
      treated with low-dose naltrexone (a glial attenuator), in combination with other
      CRPS therapies. Prominent CRPS symptoms remitted in these two patients, including
      dystonic spasms and fixed dystonia (respectively), following treatment with low
      dose naltrexone (LDN). LDN, which is known to antagonize the Toll-like Receptor 4
      pathway and attenuate activated microglia, was utilized in these patients after
      conventional CRPS pharmacotherapy failed to suppress their recalcitrant CRPS
      symptoms.

PMID- 23546885
TI  - Regional variations of antioxidant capacity and oxidative stress responses in HIV
      1 transgenic rats with and without methamphetamine administration.
AB  - HIV infection and methamphetamine (Meth) abuse both may lead to oxidative stress.
      This study used HIV-1 transgenic (HIV-1Tg) rats to investigate the independent
      and combined effects of HIV viral protein expression and low dose repeated Meth
      exposure on the glutathione (GSH)-centered antioxidant system and oxidative
      stress in the brain. Total GSH content, gene expression and/or enzymatic
      activities of glutamylcysteine synthetase (GCS), gamma-glutamyltransferase (GGT),
      glutathione reductase (GR), glutathione peroxidase (GPx), glutaredoxin (Glrx),
      and glutathione-s-transferase (GST) were measured. The protein expression of
      cystine transporter (xCT) and oxidative stress marker 4-hydroxynonenal (HNE) were
      also analyzed. Brain regions studied include thalamus, frontal and remainder
      cortex, striatum, cerebellum and hippocampus. HIV-1Tg rats and Meth exposure
      showed highly regional specific responses. In the F344 rats, the thalamus had the
      highest baseline GSH concentration and potentially higher GSH recycle rate. HIV
      1Tg rats showed strong transcriptional responses to GSH depletion in the
      thalamus. Both HIV-1Tg and Meth resulted in decreased GR activity in thalamus,
      and decreased Glrx activity in frontal cortex. However, the increased GR and Glrx
      activities synergized with increased GSH concentration, which might have
      partially prevented Meth-induced oxidative stress in striatum. Interactive
      effects between Meth and HIV-1Tg were observed in thalamus on the activities of
      GCS and GGT, and in thalamus and frontal cortex on Glrx activity and xCT protein
      expression. Findings suggest that HIV viral protein and low dose repeated Meth
      exposure have separate and combined effects on the brain's antioxidant capacity
      and the oxidative stress response that are regional specific.

PMID- 23546886
TI  - Japanese encephalitis virus infection alters both neuronal and astrocytic
      differentiation of neural stem/progenitor cells.
AB  - Japanese encephalitis virus (JEV) predominantly infects neurons and causes damage
      to the central nervous system (CNS). Neural stem/progenitor cells (NSPCs)
      constitute multi-potent stem cell population in postnatal/adult brain, with
      capacity to differentiate into neurons, astrocytes or oligodendrocytes. NSPCs are
      known to play a pivotal role in CNS repair mechanisms during various neurological
      disorders. Previous studies from our laboratory have shown that JEV infection of
      NSPCs depletes the stem-cell pool, which may result in impaired repair functions
      leading to motor and cognitive deficits in survivors. In the present study, we
      evaluated the effect of JEV infection on differentiation potential of NSPCs
      isolated from BALB/c mouse pups (Post natal day 7). Results clearly indicated
      that, JEV infection was more robust in undifferentiated NSPCs as compared to
      differentiated ones. Further, JEV infected NSPCs showed hampered differentiation
      and arrested migration in adherent neurosphere cultures. Interestingly, the
      neuronal differentiation appeared to be more severely affected by JEV as compared
      to astrocyte differentiation. The transcription factors involved in both neuronal
      and astrocyte differentiations were significantly decreased upon JEV infection.
      Overall, results presented in this study comprehensively provide first evidence
      for JEV induced alteration of neuronal and astrocyte differentiation.

PMID- 23546887
TI  - The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's
      disease and other degenerative parkinsonisms.
AB  - Based on our previous finding of the p.A382T founder mutation in ALS patients
      with concomitant parkinsonism in the Sardinian population, we hypothesized that
      the same variant may underlie Parkinson's disease (PD) and/or other forms of
      degenerative parkinsonism on this Mediterranean island. We screened a cohort of
      611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67
      cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation
      of the TARDBP gene. The p.A382T mutation was identified in nine patients with
      parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two
      with familiar forms), while four patients (6.0 % of all other forms of
      parkinsonism) presented a peculiar clinical presentation quite different from
      classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal
      cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3
      %) consistent with a founder mutation in the island population. Our findings
      suggest that the clinical presentation of the p.A382T TARDBP gene mutation may
      include forms of parkinsonism in which the extrapyramidal signs are the crucial
      core of the disease at onset. These forms can present PSP or CBD-like clinical
      signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment.
      No evidence of association has been found between TARDBP gene mutation and
      typical PD.

PMID- 23546888
TI  - Disentangling desire and arousal: a classificatory conundrum.
AB  - A controversial proposal to collapse sexual disorders of desire and arousal is
      forthcoming in the diagnostic and statistical manual of mental disorders (5th
      ed.) (DSM-5). Yet, no study has attempted to empirically distinguish these
      disorders by using explicit criteria to recruit and compare distinct groups of
      low desire and arousal sufferers. The goal of the current study was to test the
      feasibility of finding medically healthy men and women meeting clearly
      operationalized DSM-IV-TR criteria for disorders of desire and/or arousal and
      compare them to matched controls. To assess operational criteria, participants
      completed a comprehensive telephone screening interview assessing DSM-IV-TR and
      DSM-5 criteria, as well as standardized self-report measures of sexual
      functioning. The use of operationalized DSM-IV-TR criteria to recruit
      participants led to the exclusion of over 75% of those reporting sexual
      difficulties, with the primary reason for exclusion being failure to meet at
      least one central diagnostic criterion. The application of the DSM-5 criteria was
      even more restrictive and led to the exclusion of all but four men and one woman
      using the original four-symptom criteria, and four men and five women using the
      revised three-symptom criteria. Cluster analyses supported the distinction
      between desire and genital arousal difficulties, and suggest that different
      groups with distinct clusters of symptoms may exist, two of which are consistent
      with the DSM-5 criteria. Overall, results highlight the need for revisions to the
      diagnostic criteria, which, as they stand, do not capture the full range of many
      people's sexual difficulties.

PMID- 23546889
TI  - The impact factor: just the facts.

PMID- 23546890
TI  - Body satisfaction and couple's daily sexual experience: a dyadic perspective.
AB  - Although it is widely believed that body satisfaction positively affects sexual
      experience, research on this topic has been limited by an almost exclusive focus
      on women and on individuals and by an overreliance on cross-sectional self-report
      data. To address these shortcomings, the current study used 1,598 daily sex
      reports completed by 144 couples over an average of 3 weeks to investigate the
      impact of satisfaction with one's own and one's partner's body on sexual
      experience. Results indicated that an individual's satisfaction with his or her
      own body was not as important to the overall quality of sexual experience as
      one's satisfaction with the partner's body or as the partner's satisfaction with
      the individual's body. Moreover, although effects were generally similar for men
      and women, women's sexual outcomes were more strongly shaped by partner
      satisfaction with her body than the reverse. Results highlight the need to adopt
      a dyadic perspective in efforts to understand the effects of body satisfaction on
      sexual experience. 

PMID- 23546891
TI  - Sex guilt and life satisfaction in Iranian-american women.
AB  - Although the experience of sex guilt has been considered among a variety of
      ethnic groups, the area has not yet been empirically explored among Iranian
      American women. The present study investigated the relationship between sexual
      self-schema (i.e., beliefs about the sexual aspects of oneself), acculturation,
      and sex guilt, and it further examined the association between sex guilt and life
      satisfaction in Iranian American women. A total of 65 Iranian American women,
      with a mean age of 31.3 years (SD = 11.7), completed five self-administered
      questionnaires. Findings indicated a significant inverse correlation between
      sexual self-schema and sex guilt. More specifically, women who endorsed negative
      self-views regarding their sexual self reported higher levels sex guilt. Results
      revealed that acculturation was unrelated to sex guilt, when the effect of being
      Muslim or non-Muslim was controlled. Women with high sex guilt reported
      significantly lower levels of life satisfaction. Moreover, analyses for mediation
      effects supported sex guilt as a partially mediating variable between sexual self
      schema and life satisfaction. Levels of sex guilt were higher among Muslim women
      when compared to women of other religious affiliations. Additionally, Muslim
      women appeared to be significantly less acculturated to Western ideals than other
      religious groups. The present findings suggest that mental health professionals
      who provide services to Iranian American women need to consider the negative
      effects of sex guilt, particularly among Muslim women. 

PMID- 23546892
TI  - Sexual positioning and race-based attraction by preferences for social dominance
      among gay Asian/Pacific Islander men in the United States.
AB  - For gay men in the United States, race/ethnicity has been demonstrated to factor
      importantly into sexual preferences, and race-based beliefs regarding certain
      racial groups are prevalent within the gay male community. For gay men of color,
      such beliefs may differentially influence their sexual preferences. Yet, little
      is known about the social-psychological factors underlying differences in sexual
      preferences among gay men of color. The present study examined how personal
      preferences for social hierarchy and dominance may explain variations in sexual
      positioning preferences, and how this relationship may be further qualified by
      their race-based sexual attraction among gay Asian/Pacific Islander (API) men. A
      total of 141 API gay men were recruited to participate in an online survey.
      Measures assessed participants' sexual positioning preferences, race-based sexual
      attraction, and preferences for social hierarchy or social dominance orientation
      (SDO). Self-identified tops scored higher on SDO than bottoms or versatiles.
      Participants attracted to non-API men scored higher on SDO compared to
      participants attracted to API men and participants who reported no race-based
      attraction. Finally, a significant two-way interaction indicated that tops
      attracted to non-API men scored the highest on SDO, and bottoms with no race
      based attraction in men scored the lowest. Race/ethnicity is a prominent factor
      in sexual attraction and sexual positioning preferences among gay men, and one's
      proclivity for social hierarchy and dominance explains differences in sexual
      preferences among API gay men. By demonstrating how API gay men negotiate sexual
      preferences, present findings help elucidate existing race-based sexual dynamics
      within gay male culture. 

PMID- 23546893
TI  - Accurate identification of a preference for insertive versus receptive
      intercourse from static facial cues of gay men.
AB  - In intercourse between men, one of the partners typically assumes the role of an
      insertive partner (top) while the other assumes a receptive role (bottom).
      Although some research suggests that the perceptions of potential partners'
      sexual roles in gay men's relationships can affect whether a man will adopt the
      role of top or bottom during sexual intercourse, it remains unclear whether
      sexual roles could be perceived accurately by naive observers. In Study 1, we
      found that naive observers were able to discern men's sexual roles from photos of
      their faces with accuracy that was significantly greater than chance guessing.
      Moreover, in Study 2, we determined that the relationship between men's perceived
      and actual sexual roles was mediated by perceived masculinity. Together, these
      results suggest that people rely on perceptions of characteristics relevant to
      stereotypical male-female gender roles and heterosexual relationships to
      accurately infer sexual roles in same-sex relationships. Thus, same-sex
      relationships and sexual behavior may be perceptually framed, understood, and
      possibly structured in ways similar to stereotypes about opposite-sex
      relationships, suggesting that people may rely on these inferences to form
      accurate perceptions. 

PMID- 23546894
TI  - Cross-sectional relationship between chronic stress and mineral concentrations in
      hair of elementary school girls.
AB  - Chronic stress exposure is associated with diverse negative health outcomes. It
      has been hypothesised that stress may also negatively affect the body's mineral
      status. This study investigates the association between chronic stress and long
      term mineral concentrations of calcium (Ca), copper (Cu), iron (Fe), magnesium
      (Mg), phosphorus (P) and zinc (Zn) in scalp hair among elementary school girls.
      Complete information on child-reported stress estimates (Coddington Life Events
      Scale (CLES)), hair cortisone and hair mineral concentrations, and predefined
      confounders in the stress-mineral relationship (i.e. age, body mass index,
      physical activity, diet, hair colour and parental education) was provided cross
      sectionally for 140 girls (5-10 years old). The relationship between childhood
      stress measures (predictor) and hair minerals (outcome) was studied using linear
      regression analysis, adjusted for the abovementioned confounders. Hair cortisone
      concentrations were inversely associated with hair mineral concentrations of Ca,
      Mg, Zn and the Ca/P ratio. Children at risk by life events (CLES) presented an
      elevated Ca/Mg ratio. These findings were persistent after adjustment for
      confounders. This study demonstrated an independent association between chronic
      stress measures and hair mineral levels in young girls, indicating the importance
      of physiological stress-mineral pathways independently from individual or
      behavioural factors. Findings need to be confirmed in a more heterogeneous
      population and on longitudinal basis. The precise mechanisms by which stress
      alters hair mineral levels should be further elucidated.

PMID- 23546895
TI  - Combined treatment with progesterone and magnesium sulfate positively affects
      traumatic brain injury in immature rats.
AB  - AIM: It is well known that head trauma results in damage in hippocampal and
      cortical areas of the brain and impairs cognitive functions. The aim of this
      study is to explore the neuroprotective effect of combination therapy with
      magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected
      to contusion injury. MATERIAL AND METHODS: Progesterone (8 mg/kg) and MgSO4 (150
      mg/kg) were injected intraperitoneally immediately after induction of traumatic
      brain injury. Half of groups were evaluated 24 hours later, the remaining animals
      3 weeks after trauma or sham surgery. Anxiety levels were assessed with open
      field activity and elevated plus maze; learning and memory performance were
      evaluated with Morris Water maze in postnatal 27 days. RESULTS: Combined therapy
      with progesterone and magnesium sulfate significantly attenuated trauma-induced
      neuronal death, increased brain VEGF levels and improved spatial memory deficits
      that appear later in life. Brain VEGF levels were higher in rats that received
      combined therapy compared to rats that received either medication alone.
      Moreover, rats that received combined therapy had reduced hipocampus and
      prefrontal cortex apoptosis in the acute period. CONCLUSION: These results
      demonstrate that combination of drugs with different mechanisms of action may be
      preferred in the treatment of head trauma.

PMID- 23546896
TI  - Surgical management of intracranial arachnoid cysts: clinical and radiological
      outcome.
AB  - AIM: Intracranial arachnoid cysts account for 1% of all intracranial mass lesions
      and may require drainage if symptomatic. MATERIAL AND METHODS: We retrospectively
      reviewed the medical records of 45 consecutive patients who underwent surgical
      drainage for symptomatic intracranial cysts at our institution from January 2000
      to January 2010. The average age of our patients was 36.2 years; 26 were female
      and 19 were males. The most common symptoms included headaches (73.3%) and
      dizziness (35.6%). RESULTS: Cyst wall fenestration was carried out in 29 (64.4%),
      Cystoperitoneal shunting in 6 (13.3%) and endoscopic fenestration and stealth
      guided craniotomy in 5 patients each (11.1%). Seven patients had perioperative
      complications, and on discharge 79.1% of all patients had partial or complete
      clinical relief and 85.7% showed radiological decompression. A maximum cyst
      dimension of more than 5.0 cm was significantly associated with worse outcome at
      discharge (p=0.02). There was no association between post-operative size cyst
      decompression and resolution of clinical symptoms. The clinical and radiological
      outcomes were comparable between different surgical methods. CONCLUSION: There
      was no difference in the outcomes between different modalities. The extent of
      post-operative radiological reduction had no correlation with clinical outcomes,
      and should be assessed in relation to the patient's clinical status.

PMID- 23546897
TI  - The effect of intracerebroventricular injection of beta amyloid peptide (1-42) on
      caspase-3 activity, lipid peroxidation, nitric oxide and NOS expression in young
      adult and aged rat brain.
AB  - AIM: Intracerebroventricular (icv) administration of beta amyloid peptide (Abeta)
      in rats can be used to model certain aspects of Alzheimer disease (AD).The
      purpose of this study was to examine the effects of intracerebroventricular Abeta
      (1-42) peptide injection on caspase-3 activity and expression of nNOS and iNOS,
      malondialdehyde (MDA), glutathione (GSH) and NOx in the hippocampus, temporal
      cortex and parietal cortex. MATERIAL AND METHODS: Groups were defined as 1) young
      adult control, 2) Abeta (1-42) injected young adult, 3) aged control and 4) Abeta
      (1-42) injected aged group. Stereotaxic surgery was performed. Abeta (1-42)
      peptide (5MUg/1MUl, in each icv) was administered bilateral
      intracerebroventricularly as a single injection. RESULTS: Caspase-3 activity
      significantly increased in Abeta (1-42) injected aged rats when compared with
      young adult rats. Abeta (1-42) significantly increased lipid peroxidation in both
      young adult and aged rats. There was an increase in nNOS expression in the
      temporal cortex of Abeta (1-42) injected aged rats. CONCLUSION: The most
      significant increase was seen in hippocampus in caspase-3 levels of the Aged-
      Abeta 1-42 group. nNOS expression in the hippocampus of aged rats was increased
      compared to young adult rats. However, nNOX expression in the hippocampus of
      Abeta (1-42) injected aged rats decreased significantly.

PMID- 23546898
TI  - Evaluation of TGF beta1, IL-8 and nitric oxide in the serum of diffuse axonal
      injury patients and its association with clinical status and outcome.
AB  - AIM: The aim was to evaluate the level of interleukin 8 (IL-8), transforming
      growth factor beta1 (TGF beta1) and Nitric oxide (NO) in diffuse axonal injury
      (DAI) and its association to the outcome and clinical status. MATERIAL AND
      METHODS: This cross-sectional study was conducted on 20 patients with DAI and 20
      patients with multiple traumas without head injury and 20 healthy subjects as
      controls. Blood levels of IL-8, TGF beta1 and nitric oxide in the 1st, 2nd, 3rd
      and 7th days of injury were measured. Glasgow coma scale (GCS) of patients was
      recorded. The patients' outcome was evaluated by Glasgow Outcome Scale (GOS).
      RESULTS: The level of TGF beta1 was increasing during the admission and had the
      maximum level at the 7th day. In the DAI group, there was significant correlation
      between GOS score and serum IL-8 at 7th day of admission (r=-0.68, p= 0.002). In
      this group the GCS was found to be significantly correlated with the IL-8
      concentration at 7th day of admission (p= 0.026, r=-0.55). CONCLUSION: IL-8 has
      negative correlation with GCS and GOS. TGF beta1 could protect the brain from
      cytotoxics, hypoxia and acidosis so its level comes down in brain injuries as a
      result of its overuse.

PMID- 23546899
TI  - Dose dependent morphological effects of alpha lipoic acid on vasospastic femoral
      artery in rats.
AB  - AIM: The dose dependent effects of alpha lipoic acid (alpha-LA) were investigated
      morphologically on rat vasospasm model. MATERIAL AND METHODS: 32 rats were
      divided into four groups: group I=control; group II=vasospasm; group
      III=vasospasm +low dose (20 mg/kg) intraperitoneal alpha-LA administered; and
      group IV=vasospasm +high dose (100 mg/kg) intraperitoneal alpha-LA administered.
      Histological and morphometric examinations were carried out for each groups under
      light microscope. RESULTS: The mean vascular wall thickness displayed significant
      increase in group II and III compared with group I (p < .05). Statistical
      comparison of group II and IV, regarding vascular wall thickness showed a
      significant decrease in group IV, and regarding vascular lumen area showed a
      significant increase in group IV (p < .05). CONCLUSION: It is demonstrated alpha
      LA reduces the effects of vasospasm in high dose treatment group by decreasing
      the wall thickness and increasing the lumen surface area. The present study
      suggests that adequate dose of alpha-LA is a potential therapeutic agent in
      experimental vasospasm model.

PMID- 23546900
TI  - Facial nerve function after large cystic vestibular schwannomas surgery via the
      retrosigmoid approach.
AB  - AIM: To evaluate long-term postoperative facial nerve function in patients
      undergoing large cystic vestibular schwannomas (VSs) surgery. MATERIAL AND
      METHODS: Surgical outcome of 36 patients with large cystic VS was retrospectively
      assessed, and compared with a group of 67 patients with large solid VS. RESULTS:
      The anatomical integrity of the facial nerve was preserved in 88.9% of cystic
      group patients and in 92.5% of solid group patients. At 1 year after surgery,
      75.8% of the patients with cystic VSs had favorable facial nerve function and
      24.2% had poor function. There was no significant difference in facial nerve
      outcomes between cystic and solid tumors. When the cyst wall was closely adherent
      to the facial nerve, near total or subtotal resection was associated with a
      better facial nerve outcome compared to total excision (P < 0.05). CONCLUSION: In
      most cystic VS patients, favorable facial nerve function can be attained by
      surgical treatment via retrosigmoid approach. Special care should be taken to
      remove entire cystic VSs as well as partial cystic VSs with anterior or medial
      located cysts. When a dissection plane cannot be developed between the cyst wall
      and the facial nerve, near total or subtotal resection is of benefit for facial
      nerve function.

PMID- 23546901
TI  - Single-stage operation for traumatic thoracolumbar fractures with severe
      dislocation via a posterior approach alone: a case series.
AB  - AIM: This study reports a technique for treating severe thoracolumbar fractures
      with single-stage decompression, reduction, reconstruction, and stabilization via
      an entirely posterior approach. MATERIAL AND METHODS: The cases of 11 patients
      with severe traumatic thoracolumbar fractures/dislocations that were managed with
      single-stage decompression, reduction, reconstruction, and stabilization via an
      entirely posterior approach were included. Data on age, sex, mechanism of injury,
      associated trauma, neurological status, surgical technique, and clinical outcome
      were reviewed retrospectively. RESULTS: Of the 11 patients, two presented with
      primarily coronal displacement and nine with sagittal displacement. Coronal
      displacement was corrected from 19% preoperatively to 4.0% at the last follow-up
      evaluation. Sagittal displacement was reduced from 73.0% preoperatively to 3.0%
      at the last follow-up evaluation. After a mean follow-up period of 20.7 (range 16
      30) months, no patient complained of local pain and no significant loss of
      correction or hardware failure was observed. CONCLUSION: Our experience proves
      that the single-stage posterior approach is safe and biomechanically reliable for
      treating severe thoracolumbar fractures/dislocations. Therefore, the presented
      technique is an alternative approach for this rare injury.

PMID- 23546902
TI  - Stent-jail technique in endovascular treatment of wide-necked aneurysm.
AB  - AIM: To describe a reconstructive technique using single stent for wide-necked
      aneurysms. MATERIAL AND METHODS: This technique was described as stent-jail
      technique consisting of the aneurismal catheterization before the deployment of a
      self-expandable stent across the aneurysm neck. Following the deployment of the
      stent, embolization coils were delivered with the microcatheter positioned within
      the aneurysm dome and wedged between the stent and the aneurysm dome. The
      microstents, such as Neuroform, Leo and Wingspan stents, were used in in our
      series for electively treated aneurysms. RESULTS: During a 3-year period,13
      patients with wide-necked aneurysms were treated electively with this technique.
      The aneurysms arose from the internal carotid artery (5), anterior cerebral
      artery (4), anterior communicating artery (1), vertebral artery ( 1), middle
      cerebral artery (1) and middle cerebral artery (1). Thirteen stents (6 Leo
      stents, 4 Neuroform stents and 3 Wingspan stents) were successfully deployed
      across the aneurysm neck to constrain subsequent embolization coils of a wide
      necked cerebral aneurysm. None of the patients experienced any periprocedural or
      delayed neurological complications. This maneuver enabled us to support the coil
      loops within the aneurismal sac with stabilization of the microcatheter.
      CONCLUSION: The stent-jail technique represents an efficacious adjuvant technique
      to assist coiling of selected wide-necked cerebral aneurysms. This technique is
      particularly helpful for wide-necked aneurysms.

PMID- 23546903
TI  - The value of touch imprint cytology of core needle biopsy in the diagnosis of
      spinal lesions.
AB  - AIM: We aimed to investigate the contribution of the touch imprint cytology (TIC)
      of core needle biopsies (CNBs) to the diagnosis in spinal lesions. MATERIAL AND
      METHODS: Sixty cases with spinal CNB and TIC were included in the study.
      Hematoxylin and Eosin (H&E) and May-Grunwald- Giemsa (MGG) stained TIC slides and
      CNB of each case were blindly reevaluated by two pathologists. TIC and CNB
      findings were categorized as follows: 1-Nondiagnostic 2- Benign nonneoplastic 3-
      Benign neoplastic 4- Malignant 5-Malignant lesions that can be typed. RESULTS:
      TIC and CNBs were nondiagnostic in 62% and 45% of all cases, respectively.
      Malignancy could be identified and typed in 23% of imprint preparations and 35%
      of CNBs. When TIC and CNB diagnosis were compared, it was seen that diagnostic
      categories were just the same in 70% of the cases. In 37% of the cases benign and
      malignant groups could be distinguished. In 20% of the cases diagnostic
      categories were totally different. CONCLUSION: The percentage of the
      nondiagnostic material in CNBs can reach up to 45%. The findings in TIC and CNBs
      were compatible with each other. We observed that TIC was diagnostic on its own
      especially in carcinoma metastasis and contributed to the assessment of cytologic
      detail in hematologic malignancies.

PMID- 23546904
TI  - Posterior dynamic stabilization for the treatment of patients with lumbar
      degenerative disc disease: long-term clinical and radiological results.
AB  - AIM: Comparison of long-term preoperative and postoperative clinical and
      radiological results for patients diagnosed with degenerative disc disease that
      underwent posterior dynamic stabilization. Lumbar disc degeneration is caused by
      a variety of factors. Disruptions in the vertebral endplate result in defects in
      disc nutrition and, thus, disc degeneration. The aims of dynamic stabilization
      are to unload the disc/facet joints, preserve motion under mechanical load, and
      restrict abnormal motion in the spinal segment. MATERIAL AND METHODS: Twenty-five
      patients diagnosed with lumbar degenerative disc disease were enrolled. Totally,
      25 vertebral segments were subjected to posterior dynamic stabilization. Patients
      were clinically evaluated in the preoperative and postoperative periods using the
      Oswestry Disability Index (ODI) and Visual Analog Scale (VAS). Segmental movement
      was evaluated radiologically in the late postoperative period by measuring the
      segmental angles during flexion and extension. RESULTS: Significant postoperative
      improvements were observed in the ODI and VAS measurements (P < 0.01). During the
      long postoperative period (averaging 5 years and 2 months), lumbar lordosis
      angles, intervertebral space ratio and segmental ratio were measured and compared
      statistically. Adjacent segment disease developed in two patients. Both patients
      received L5-S1 discectomy. CONCLUSION: Good clinical outcomes were observed in
      the treatment of lumbar degenerative disc disease with a posterior dynamic
      system.

PMID- 23546905
TI  - Missed injury in patients with severe traumatic brain injury complicated by
      multiple trauma.
AB  - AIM: The aim of this study was to investigate retrospectively the multiple
      injuries prone to be missed in 432 cases. MATERIAL AND METHODS: The cases were
      divided into two groups, i.e., whether the missed injury was found during
      admission or follow up. The mean ISS value, ratio of patients of cases with GCS <
      8, and mortality were calculated and compared. The incidences of missed diagnosis
      of various body parts were calculated and compared with one another to identify
      the multiple injuries prone to be missed during the diagnosis for severe
      traumatic brain injury patients accompanied by multiple trauma. RESULTS: Among
      the 432 patients, 54 patients had missed injuries. The mean ISS value and the
      ratio of patients of cases GCS < 8 in the missed group were higher compared with
      those in the non-missed group. The missed diagnosis ratio of various body parts
      had significant differences. Injuries in the optic nerve and abdomen were the
      more often missed injuries in the diagnosis. CONCLUSION: The multiple trauma
      severity and coma degree impact diagnoses for severe TBI complicated by multiple
      injuries is highly accurate. The early diagnosis of injury is of the highest
      importance so that the injury may be treated immediately.

PMID- 23546906
TI  - Supracondylar transjugular tubercle approach to intradural lesions anterior or
      anterolateral to the craniocervical junction without resection of the occipital
      condyle.
AB  - AIM: To clarify the usefulness of supracondylar transjugular tubercle approach
      for treatment intradural lesions anterior and anterolateral to foramen magnum, in
      which the posterior portion of the jugular tubercle is removed extradurally
      through the condylar fossa with the atlanto-occipital joint intact. MATERIAL AND
      METHODS: The supracondylar transjugular tubercle approach was applied to 28
      craniocervical junction surgeries. These surgeries included clipping a vertebral
      artery aneurysm in 12 cases and removing intradural tumors ventral and
      ventrolateral to foramen magnum in 16 cases. RESULTS: The approach offered very
      good visualization of the anterior and anterolateral part of the craniocervical
      junction region and sufficient working space. These surgeries were performed
      safely without major complications. In all 12 cases, the aneurysm was easily
      clipped without any problems. In 16 cases of tumors, 14 tumors were totally
      removed, the remaining 2 cases achieved subtotal resection due to medullary
      invasion of tumors. CONCLUSION: Supracondylar transjugular tubercle approach
      offered very good visualization of the anterior and anterolateral part of the
      craniocervical junction region and can be an ideal approach for accessing
      intradural lesions anterior and anterolateral part of the craniocervical junction
      region.

PMID- 23546907
TI  - Effects of intracisternal and intravenous dexmedetomidine on ischemia-induced
      brain injury in rat: a comparative study.
AB  - AIM: To compare the effect of dexmedetomidine administered by intracisternal
      route with by intravenous route on brain tissue of rat after incomplete cerebral
      ischemia. MATERIAL AND METHODS: Cerebral ischemia was produced by the combination
      of right common carotid artery occlusion and hemorrhagic hypotension during 30
      minutes. Thirty minutes before the ischemia, 0.1 ml 0.9% NaCl (Group SIC, n=6) or
      9 MUg/kg dexmedetomidine (Group DIC, n=6) was administered into the cisterna
      magna. For the intravenous groups, 9 MUg/kg dexmedetomidine (Group DIV, n=6) or
      0.9% NaCl (Group CONTROL, n=6) 5 ml/kg/h was given in 2 hours. After 24 hours,
      the lipid peroxidation levels were measured in the brain tissue and plasma.
      Hippocampal formations were used for histopathological examination. RESULTS:
      Intravenous dexmedetomidine produced a decrease in baseline mean arterial blood
      pressure and plasma glucose concentrations. There was a significant difference
      between the DIV group and DIC, SIC, CONTROL groups regarding the brain lipid
      peroxidation levels (p < 0.001, p < 0.001, p=0.001, respectively), and regarding
      the picnotic neuronal cell count (p < 0.001, p=0.01, p=0.009, respectively). Mean
      plasma lipid peroxidation levels of the DIV group was different from the DIC
      group (p=0.003). CONCLUSION: Systemically administered dexmedetomidine had
      neuroprotective effect in ischemia-induced neuronal damage, but centrally
      administered dexmedetomidine did not.

PMID- 23546908
TI  - MR cisternography in the posterior fossa: the evaluation of trigeminal
      neurovascular compression.
AB  - AIM: To evaluate the utility of 3D-magnetic resonance cisternography(MRC) of
      posterior cranial fossa in visualizing trigeminal neurovascular compression in
      patients with trigeminal neuralgia. MATERIAL AND METHODS: 146 consecutive
      patients in the period from June 2010 to July 2011 in our institute diagnosed
      with trigeminal neuralgia underwent MRC on the posterior cranial fossa. MR
      devices used for MRC included two sets of 3.0 tesla and one set of 1.5 tesla. The
      hydrography sequences for MRC included 3D-SPACE and 3D-DRIVE. RESULTS: In total,
      75 patients (51.4%) were found with trigeminal neurovascular compression on MRC.
      Among them, 25 patients underwent microvascular decompression. Intraoperatively,
      20 patients (80%) had related arteries consistent with imaging manifestations on
      MRC. Nevertheless, the arterial compression combined with petrosal vein could not
      be identified on MRC in 3 of the 20 patients. In the inconsistent 5 cases, the
      involved vessels were confirmed as superior petrosal veins during the surgery.
      CONCLUSION: 3D-MRC has prominent clinical value in determining the trigeminal
      neurovascular compression and identifying the related vessels. However, MRC does
      have certain limitations on identifying petrosal vein compression.

PMID- 23546909
TI  - Incidence, hormonal distribution and postoperative follow up of atypical
      pituitary adenomas.
AB  - AIM: To assess the incidence, hormonal activity and postoperative follow up of
      the cases that are histopathologically diagnosed as atypical pituitary adenoma
      (APA) in our series. MATERIAL AND METHODS: In this study, 13 atypical pituitary
      adenoma cases, by the WHO 2004 criteria, among the 146 pituitary adenoma patients
      operated on in our clinic between January 2009 and May 2012 by endoscopic
      endonasal transsphenoidal approach were included. RESULTS: In histological
      studies, 133 cases were diagnosed as typical pituitary adenoma (91.1%) and 13
      cases were APAs (8.9%) of which 10 were male (76.9%) and 3 were female (23.1%),
      ranged between 27 and 80 (mean 52.7) ages. Histopathological distribution of APAs
      was 9 nonsecretory adenomas (69.3%), 3 prolactinomas (23.1%) and 1
      somatostatinoma (7.6%). Asymptomatic pituitary apoplexy was diagnosed in 4 cases
      (30.7%). Eleven cases of typical pituitary adenomas (8.2%) and 5 cases of the
      atypical pituitary adenomas (38.4%) were re-operated due to tumor recurrences.
      CONCLUSION: Accurate histopathological examination shows that atypical pituitary
      adenoma is not a rare disease. Although it is not the only determinant, APAs are
      more prone to recurrence than typical adenomas. In our opinion, if total
      resection is not possible for the patients with APA, close postoperative follow
      up and additional curative therapy modalities are needed.

PMID- 23546910
TI  - Stent placement for the treatment of complex internal carotid bifurcation
      aneurysms: a review of 16 cases.
AB  - AIM: Stent placements for the treatment of complex internal carotid bifurcation
      aneurysms are not well documented yet. In this article, we reported a series of
      16 such cases to evaluate the feasibility, safety and effectiveness of stent
      placement for these particular lesions. MATERIAL AND METHODS: Between June 2001
      and August 2011, 16 patients with 16 ICA bifurcation aneurysms were treated by
      stent assisted coiling at our institution. Their clinical data, treatment results
      and follow-up were retrospectively collected and analyzed. RESULTS: Sixteen
      stents, including 10 Enterprise, 4 Neuroform, 1 Solitaire and 1 one balloon
      mounted coronary stent (BX), were successfully deployed in this series. Immediate
      angiogram showed complete occlusion in 5, neck remnant in 2 and residual sac in
      9. No procedure-related complication occurred. Angiographic follow-up results
      (mean, 12.1 months) were available in 15 patients, 9 of the aneurysms were cured,
      1 was improved, 3 were stable, 2 were recanalized, and 1 was retreated. Clinical
      follow-up (mean, 28.6 months) of all 16 patients demonstrated no neurologic
      deterioration or rebleeding. CONCLUSION: Our result suggests that stent placement
      for the treatment of complex ICA bifurcation aneurysms is feasible and safe.
      However, its efficacy should be further evaluated by larger case series and more
      adequate follow-up.

PMID- 23546911
TI  - Microvascular decompression for hemifacial spasm due to four offending vessels: a
      case report.
AB  - A 65-year-old woman presented with left facial involuntary movement and facial
      palsy for eight years. Brain magnetic resonance image (MRI) and magnetic
      resonance angiography (MRA) revealed multiple vascular compression of facial
      nerve root exit zone (REZ). Standard retromastoid suboccipital craniectomy and
      arachnoid dissection were performed. Right vertebral artery (VA), left VA, left
      anterior inferior cerebellar artery (AICA), and left posterior inferior
      cerebellar artery (PICA) compressed the facial nerve in that order. The offending
      vessels were dissected away from the facial nerve and transposed sequentially.
      Teflon was interposed between the arteries and the nerve. Electrophysiological
      monitoring showed disappearance of the abnormal hemifacial spasm response during
      the operation. The offending vessels were right VA, left VA, left AICA, and left
      PICA. Postoperatively, the patient's involuntary movement was completely
      resolved. We report a rare case of hemifacial spasm caused by four offending
      vessels that was treated by microvascular decompression (MVD) with wide arachnoid
      dissection.

PMID- 23546912
TI  - Cerebral hernia caused by a thoracic surgery for multiple schwannomas in a
      patient with Neurofibromatosis type 2.
AB  - Schwannoma is a benign nerve sheath tumor composed of Schwann cells. A solitary
      schwannoma in the thorax is not rare, but a patient with Neurofibromatosis type 2
      (NF2) and multiple thoracic schwannomas is extremely rare. We report the case of
      a 27-year-old woman with NF2 and two large schwannomas in her mediastinum and
      chest wall. We performed thoracic surgery on the patient, but she developed a
      cerebral hernia immediately after the operation. We report this case in order to
      analyze the relationship between the operation and cerebral hernia and find a way
      to prevent this consequence in the future. We conclude that a cranial MRI must be
      performed for patients with multiple thoracic schwannomas before the surgery. If
      there is a tumor inside the cranium, the disease in the brain must be treated
      first to prevent the occurrence of cerebral hernia or hemorrhage.

PMID- 23546913
TI  - Dural carotico-cavernous fistula: pre and postembolization appearances of bone
      subtracted CT angiography.
AB  - Digital subtraction angiography (DSA) is the best method of evaluating carotid
      cavernous fistulas (CCF). DSA, however, has the disadvantage of being an invasive
      procedure. Computerized tomography (CT) angiography which is noninvasive, have
      been shown to provide more information about the size and location of fistulas.
      As a new method, Bone-Subtraction CT Angiography (BSCTA), than conventional CT
      angiography, is a method that improves the detection and interpretation of
      vascular lesions near to the cavernous segment of carotid artery. In this case
      report, we report a case of a dural carotico-cavernous fistula (CCF), appearances
      of pre and postembolization BSCTA images, confirmed by on DSA. As far as we know,
      CCF demonstrated by BSCTA has not been reported yet.

PMID- 23546914
TI  - Intracranial blastomycosis presenting as an enhancing cerebellopontine mass.
AB  - Isolated Blastomyces dermatitidis infection of the central nervous system is an
      uncommonly encountered entity. If left untreated it can be fatal; thus accurate
      diagnosis in a timely manner is critical. A 37-year-old white male presented with
      a severe headache. An MRI scan revealed a right-sided enhancing cerebellopontine
      angle mass with extension into the internal acoustic canal and diffuse basilar
      enhancement. After thorough assessment of the patient, an open surgical biopsy of
      the lesion was performed for pathological evaluation. The biopsy demonstrated
      broad-based budding yeasts. The cerebrospinal fluid antigen enzyme immunoassay
      (EIA) (MVista(r)) for Blastomyces dermatitidis was also positive with a level of
      4.28 EIA units.

PMID- 23546915
TI  - Spondylocostal dysostosis associated with type I split cord malformation and
      double nipple on one side: a case report.
AB  - Jarcho Levin syndrome is a rare genetic disorder characterized by multipl
      vertebral and costal anomalies at birth. Jarcho Levin syndrome includes two
      phenotypic groups: spondylothoracic dysostosis and spondylocostal dysostosis. The
      prognosis of spondylothoracic dysostosis has worse than spondylocostal
      dysostosis, because of respiratory complications. Associated malformations
      include those of the congenital heart disease, urogenital malformation, skeletal
      anomalies and neural tube defects. We present a patient with spondylocostal
      dysostosis, who also had type I split cord malformation, tethered cord, scoliosis
      and double nipple on the right. Although the association of spondylocostal
      dysostosis and type I split cord malformation is very rare, double nipples on one
      side is no previously reported.

PMID- 23546916
TI  - Brown tumors of the anterior skull base as the initial manifestation of true
      normocalcemic primary hyperparathyroidism: report of three cases and review of
      the literature.
AB  - Brown tumor is a bone lesion secondary to hyperparathyroidism of various
      etiologies. Skeletal involvement in primary hyperparathyroidism secondary to
      parathyroid adenoma is very uncommon and brown tumor has become extremely a rare
      clinical entity. Hyperparathyroidism is usually associated with high levels of
      serum calcium. Brown tumor as the only and initial symptom of normocalcemic
      primary hyperparathyroidism is extremely rare. Moreover, involvement of the skull
      base and the orbit is exceedingly rare. The authors would report three cases of
      brown tumor of the anterior skull base that were associated with true
      normocalcemic primary hyperparathyroidism. Clinical manifestations, neuroimaging
      findings, pathological findings, diagnosis and treatment of the patients are
      discussed and the relevant literature is reviewed.

PMID- 23546917
TI  - Dumbbell-shaped primitive neuroectodermal tumor mimicking trigeminal schwannoma:
      a case report and review of literature.
AB  - Primitive neuroectodermal tumor (PNET) is presumably of neural crest origin, and
      cases of supratentorial PNET in adult are extremely rare. We reported a case of
      PNET presenting as a dumbbell-shaped tumor at the middle cranial fossa of skull
      base mimicking trigeminal schwannoma both clinically and radiologically. The
      patient underwent surgery on July 13, 2010, using a combination of subtemporal,
      pterional and retrosigmoid approaches, to achieve decompression and obtain a
      histological diagnosis. The patient worsened neurologically two weeks after
      surgery. Her consciousness level became comatose due to tumor bleeding with
      compression of the brain stem and her precarious physical condition prevented
      receiving further treatment with adjuvant radiation therapy and chemotherapy. The
      correct diagnosis of PNET is important because its management differs
      dramatically from that for trigeminal schwannoma.

PMID- 23546918
TI  - Thoracic spinal epidural angiolipoma: report of two cases and review of the
      literature.
AB  - AIM: Spinal angiolipoma is a benign uncommon neoplasm composed of mature
      lipocytes admixed with abnormal blood vessels, and accounts for only 0.14-1.2% of
      all spinal tumors. MATERIAL AND METHODS: Retrospective data analysis. RESULTS: We
      report two cases of a 64-year-old woman and a 65-year-old man with thoracic
      myelopathy due to spinal angiolipoma. Magnetic resonance imaging showed
      isointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging and
      enhance with gadolinium administration. In one case, angiography elucidated the
      vascularity of the tumor and the relationship with concomitant hemangioma.
      Laminoplasty was performed to achieve tumor resection, and the postoperative
      course was uneventful with neurological improvement. Histopathological
      examination of the resected tumors revealed angiolipomas. CONCLUSION: Although
      extremely rare, thoracic spinal epidural angiolipoma should be considered in the
      differential diagnosis of thoracic spinal lesions. Prognosis after surgical
      management of this lesion is favorable. Angiography was useful for preoperative
      evaluation of vascularity and the relationship with concomitant tumors.

PMID- 23546919
TI  - Reversible focal radiological changes due to non-convulsive status epilepticus of
      the right parietooccipital lobe.
AB  - We describe a 62-year-old woman suffering from visual hallucination due to focal
      status epilepticus investigated by means of Magnetic Resonance Imaging (MRI),
      Magnetic Resonance Angiography (MRA), Electroencephalography (EEG), and 99m
      Technetium ethylcysteinate dimer Single Photon Emission Computed Tomography (Tc
      99m ECD SPECT). EEG showed spikes in the right parietooccipital area. MRI
      demonstrated gyral swelling and signal hyperintensity in the right
      parietooccipital cortex with effacement of adjacent cortical sulci on T2-
      weighted and Fluid Attenuation Inversion Recovery (FLAIR) images. MRA indicated
      localized dilation of the right posterior cerebral artery (PCA) and parietal
      branch of the right middle cerebral artery (MCA), corresponding to the epileptic
      area shown on EEG. Hyperperfusion in the right parietooccipital lobe was observed
      by Tc-99m ECD SPECT. All these findings completely resolved on the follow-up
      studies 2 months later. We present the case showing the transient radiological
      alterations on MRA corresponding to the epileptic area.

PMID- 23546920
TI  - Hemifacial spasm and recurrent stroke due to vertebrobasilar dolichoectasia
      coexisting with saccular aneurysm of the basilar artery: a case report.
AB  - We describe a patient presented with sequential events of hemifacial spasm,
      cerebral infarction and fatal subarachnoid hemorrhage. All of them are seemingly
      separate entities. Radiological examination revealed that the cause was
      vertebrobasilar dolichoectasia (VBD) coexisting with a giant saccular aneurysm of
      basilar artery. VBD is a dilatation and elongation of vertebral artery (VA) and
      basilar artery (BA) which is of different mechanism from saccular aneurysm. The
      condition is very rare and its progression may result in compression of brainstem
      and cranial nerves, ischemic and/or hemorrhagic stroke. The treatment of such
      condition is difficult and further research on the risk stratification of VBD for
      predicting stroke. Close monitoring and aggressive surgical interventions might
      be needed for high-risk patients.

PMID- 23546921
TI  - Transoral protrusion of a peritoneal catheter due to gastric perforation 10 years
      after a ventriculoperitoneal shunting: case report and review of the literature.
AB  - Various complications following ventriculoperitoneal (VP) shunting have been
      reported but transoral protrusion of peritoneal catheter is a very rare
      situation. This case is the first adult with a transoral VP shunt protrusion in
      available literature. A 47-year-old female with pseudotumor cerebri admitted
      after the peritoneal catheter protruded from her mouth during retching.
      Endoscopic examination showed a catheter inside stomach entered through the
      anterior surface. The patient was treated via VP shunt extraction and remained
      stable. Extrusion of peritoneal catheter through vagina, anus, scrotal skin or
      gastrostomy wound is well-known. However transoral protrusion should be
      considered as a very rare complication of VP shunting, especially in an adult. We
      present a rare case of transoral protrusion of a peritoneal catheter 10 years
      after ventriculo-peritoneal shunting procedure and review of the literature
      through this article.

PMID- 23546922
TI  - Vertebral arteriovenous fistulae (AVF) in neurofibromatosis type 1: a report of
      two cases.
AB  - Spontaneous vertebral arteriovenous fistulae (AVF) associated with
      neurofibromatosis Type 1 (NF-1) is a rare occurrence in the previous reports. We
      presented two female NF-1 patients with a diagnosis of cervical vertebral AVF
      treated with endovascular approach. The fistula in the first case was
      successfully obliterated by feeder occlusion; whereas, for the second one, new
      fistulae were formed following the primary fistula closure. Anatomic and
      hemodynamic changes in combination with dysplastic vascular condition in NF-1 may
      contribute to fistulae formation de novo. The present case points out a rare
      challenge encountered in the treatment of vertebral arteriovenous fistula
      complicated by previous fistula obliteration in NF-1.

PMID- 23546923
TI  - Contralateral acute subdural hematoma after surgical evacuation of the initial
      hematoma: two case reports and review of the literature.
AB  - Remote intracranial hemorrhages after craniotomy or craniectomy may rarely
      develop. As the sparse literature on this phenomenon has focused on contralateral
      intraparenchymal and epidural clots, only seven cases of postoperative
      contralateral acute subdural hematomas have been reported in the literature. We
      presented two patients who developed contralateral acute subdural hematomas after
      surgical evacuation of their initial hematomas. Case 1: A 19-year-old male fell
      from a height. CT scan revealed a left parietal acute epidural hematoma. A left
      craniotomy and epidural hematoma evacuation were performed; however, the brain
      expanded towards the craniotomy site. Dural incision revealed a thick subdural
      hematoma. Evacuation of the subdural hematoma was performed. The bone flap was
      not replaced. An emergency CT scan revealed a right acute subdural hematoma, and
      a right decompressive craniectomy and hematoma evacuation were performed. Case 2:
      A 7-year-old boy was hit by a motor vehicle. CT scan revealed a right
      frontotemporal acute subdural hematoma. A right decompressive craniectomy and
      subdural hematoma evacuation were performed; however, the brain expanded towards
      the craniectomy site. An emergency CT scan revealed a left acute subdural
      hematoma. We also reviewed the literature and discussed about these
      characteristics.

PMID- 23546924
TI  - Drug shortages in Canadian anesthesia: a national survey.
AB  - BACKGROUND: Canadian physicians are faced with an increasing frequency of drug
      shortages. We hypothesized that drug shortages have a clinical impact on
      anesthesia care in Canada. METHODS: We conducted a self-administered survey of
      anesthesiologists in Canada using the membership list of the Canadian
      Anesthesiologists' Society. For survey development, we identified key domains,
      including types of drug shortages, impact on the ability of anesthesia
      practitioners to provide general anesthesia care, and impact on patient outcomes.
      We undertook assessments of face validity, clinical sensibility, and content
      validity. Respondents were surveyed from January-April 2012. RESULTS: Completed
      valid questionnaires were submitted by 1,187 respondents (61.4%), and 779 (65.7%)
      of respondents described a shortage of one or more anesthesia or critical care
      drugs. Changes in anesthesia practice resulting from drug shortages were common;
      586 (49%) respondents thought they had given an inferior anesthetic, and 361
      (30%) reported administering medications with which they were unfamiliar.
      Respondents also reported that drug shortages were, at times, responsible for
      changes in the conduct of patient care, with 28 (2.4%) noting cancellation or
      postponement of surgery and 92 (7.8%) witnessing a drug error. One hundred sixty
      five (13.9%) respondents regarded drug shortages as having prolonged recovery
      from anesthesia, and 124 (10.5%) viewed drug shortages as resulting in an
      increased number of postoperative complications, such as postoperative nausea and
      vomiting. INTERPRETATION: Drug shortages are common in anesthetic practice in
      Canada. This state of affairs may have a negative effect on how anesthesiologists
      practice anesthesia and may be associated with adverse patient outcomes.

PMID- 23546925
TI  - Isolated cor triatriatum sinistrum and pregnancy: case report and review of the
      literature.
AB  - PURPOSE: Isolated cor triatriatum sinistrum (CTS) is a heart malformation in
      which a perforated fibromuscular membrane divides the left atrium into two
      chambers. When communication between these chambers is restricted, a patient may
      have signs and symptoms of mitral stenosis. The later stages of pregnancy are
      associated with tachycardia and increases in intravascular volume. We describe
      how this altered physiology may affect pregnant women with asymptomatic CTS. We
      also review the literature relating to pregnancy in patients with CTS. CLINICAL
      FEATURES: A 30-yr-old primigravida, at 40 weeks of gestation with pre-pregnancy
      diagnosed asymptomatic CTS, was admitted for delivery. She had no cardiac
      symptoms during pregnancy, and her vaginal delivery under epidural analgesia was
      uneventful. This cardiac malformation is infrequently described in pregnant
      women, but a literature review showed that the physiology of late pregnancy with
      increases in hemodynamic variables may result in cardiac decompensation.
      CONCLUSION: While our patient with isolated CTS and an unrestrictive intra-atrial
      membrane had an asymptomatic pregnancy and an uneventful labour, the literature
      review suggests that the increase in intravascular volume and heart rate that
      occurs during late pregnancy and after delivery may result in cardiac
      decompensation, even in patients with asymptomatic CTS.

PMID- 23546926
TI  - Turing patterns from dynamics of early HIV infection.
AB  - We have developed a mathematical model for in-host virus dynamics that includes
      spatial chemotaxis and diffusion across a two-dimensional surface representing
      the vaginal or rectal epithelium at primary HIV infection. A linear stability
      analysis of the steady state solutions identified conditions for Turing
      instability pattern formation. We have solved the model equations numerically
      using parameter values obtained from previous experimental results for HIV
      infections. Simulations of the model for this surface show hot spots of
      infection. Understanding this localization is an important step in the ability to
      correctly model early HIV infection. These spatial variations also have
      implications for the development and effectiveness of microbicides against HIV.

PMID- 23546927
TI  - Second Sino-American Conference on Nuclear Medicine.

PMID- 23546928
TI  - FDA AD Drug Development Guidance.

PMID- 23546929
TI  - SNMMI/AACR Meeting looks at molecular imaging in cancer biology and therapy.

PMID- 23546931
TI  - SNMMI offers education, exhibits, and networking in Vancouver.

PMID- 23546933
TI  - Accelerated reactive oxygen scavenging system and membrane integrity of two
      Panicum species varying in salt tolerance.
AB  - Plant exhibits various patterns of survival under salinity and their growth and
      development depend on their capacity to overcome the stress. Present
      investigation was focused on the response and regulation of the antioxidant
      defense system and the level of lipid peroxidation in Panicum miliacium and
      Panicum sumatrense under salt treatments. NaCl stress was imposed for 20 days
      after sowing of two Panicum species. The changes in the antioxidant enzyme
      activity like superoxide dismutase, catalase, peroxidase, and ascorbate
      peroxidase and the rate of lipid peroxidation level in terms of malondialdehyde
      (MDA) were recorded in both Panicum species. A great correlation exists between
      the antioxidant enzymes and lipid peroxidation. The defense mechanism activated
      in Panicum species studied was confirmed by the increased antioxidant enzyme
      activities under progressive NaCl stress. MDA content remained close to control
      at moderate NaCl concentrations and increased at higher salinities. Although
      lipid peroxidation increased in both Panicum species under salt stress the
      percent of increase was low in P. sumatrense indicating its salt-tolerant nature.
      Another possible conclusion is that improved tolerance to salt stress may be
      accomplished by increased capacity of antioxidative system.

PMID- 23546932
TI  - Evolutionary origins of human handedness: evaluating contrasting hypotheses.
AB  - Variation in methods and measures, resulting in past dispute over the existence
      of population handedness in nonhuman great apes, has impeded progress into the
      origins of human right-handedness and how it relates to the human hallmark of
      language. Pooling evidence from behavioral studies, neuroimaging and
      neuroanatomy, we evaluate data on manual and cerebral laterality in humans and
      other apes engaged in a range of manipulative tasks and in gestural
      communication. A simplistic human/animal partition is no longer tenable, and we
      review four (nonexclusive) possible drivers for the origin of population-level
      right-handedness: skilled manipulative activity, as in tool use; communicative
      gestures; organizational complexity of action, in particular hierarchical
      structure; and the role of intentionality in goal-directed action. Fully testing
      these hypotheses will require developmental and evolutionary evidence as well as
      modern neuroimaging data.

PMID- 23546934
TI  - Correlation between cerebral infarction and ALOX5AP gene expression.
AB  - Linkage/linkage-disequilibrium analysis studies, based on positional information
      and gene function, indicated that ALOX5AP gene was an independent risk factor of
      cerebral infarction in humans; however, this needs to be verified among different
      populations. Herein, we verified whether ALOX5AP was a risk factor of cerebral
      infarction in the Chinese Han population. For this purpose, 547 cerebral
      infarction patients were enrolled as the case group; the control group comprised
      794 healthy, age-matched individuals unrelated to case group and had no history
      of cerebral infarction/transient ischemic attack. Regarding single-nucleotide
      polymorphism (SNP) selection and ALOX5AP genotyping, we selected four SNP loci
      (SG13S25, SG13S114, SG13S89, and SG13S32) and determined allelic frequencies.
      Genotyping of SG13S114 and SG13S32 adopted a method of combining real-time
      quantitative PCR and allele-specific PCR. A linkage-disequilibrium analysis of
      ALOX5AP was also performed. We found that the allelic frequencies of SG13S25 and
      SG13S89 were below 5% and those of SG13S114 and SG13S32 were above 5%. We did not
      find any differences between the case and control groups regarding allele, allele
      types, and haplotype gene frequencies of two SNP loci. The results indicate that
      the two genetic polymorphisms of ALOX5AP, SG13S114 and SG13S32, are not
      associated with cerebral infarction in Chinese Han population.

PMID- 23546935
TI  - Clinical benefit of delamanid (OPC-67683) in the treatment of multidrug-resistant
      tuberculosis patients in China.
AB  - The cure rates are much lower for multidrug-resistant (MDR) tuberculosis (TB)
      patients. Delamanid (OPC-67683) has been evaluated in phase-II MDR-TB clinical
      trials. Herein, we reviewed MDR-TB cases in which treatment regimens,
      with/without delamanid, were administered. Thirty-eight patients were enrolled;
      26 received delamanid-containing regimens (treatment group) while 12 received
      placebo-containing regimens (control group) for 56 days. Data regarding
      clinical/radio-microbiological characteristics, drug tolerability, and treatment
      outcomes were collected. We found that all patients had isolates resistant to a
      median of 5 (range 2-7) drugs; 24 (92.3%) patients in treatment group and 11
      (91.7%) in control group had cavities. Culture conversion was obtained in 32
      pulmonary TB cases (median 74.5 days). At data censure, 30/38 patients
      successfully completed therapy with documented negative cultures for at least 18
      months before the end of treatment. Two patients (5 consecutive negative
      cultures) are still on treatment. Six patients had poor outcome (3 failures/2
      lost/1 death). In 13 patients, adverse events were observed that included mental
      disorder, QT interval prolongation, and increased blood cortisol whereas only 3
      patients stopped delamanid treatment because of adverse events. It was,
      therefore, concluded that delamanid was well-tolerated, had low rates of
      discontinuation, and could be effective for treating MDR-TB.

PMID- 23546936
TI  - Coronary heart disease diagnosis bases on the change of different parts in
      treadmill exercise test ECG.
AB  - Summarize the value of the change of different parts in treadmill exercise test
      (TET) ECG to coronary heart disease (CHD) diagnosis. Four hundred and forty-five
      cases have been included in this investigation, which stayed in our hospital from
      January of 2006 to March of 2011 and underwent TET and coronary arteriography
      (CAG). The change of different parts in TET ECG in these patients had been
      retrospective summarized to determine its diagnosis value to CHD. (1) In the 445
      cases of TET testers, 200 cases showed positive in TET with 150 cases of positive
      CAG, and 50 cases of negative CAG; 245 cases showed negative in TET with 206
      cases of negative CAG, and 39 cases of positive CAG. The diagnosis sensitivity of
      CHD was 79.36% (150/189), the specificity was 80.47% (206/256), positive
      prediction value was 75.00% (150/200), negative prediction value was 84.08%
      (206/245), and false-positive rate was 25.00% (50/200) with prediction accuracy
      of 80.00% (356/445). (2) In the 200 cases with positive TET: 51 cases were in the
      limb lead group; 73 cases were in the chest lead group; and 76 cases were in the
      limb lead + chest lead group. There were 150 cases showing positive in CAG: 22
      cases were in the limb lead group; 58 cases were in the chest lead group; and 70
      cases were in the limb lead + chest lead group. The positive diagnosis rate of ST
      change in the chest lead was obviously higher than that of simple limb lead group
      (P < 0.05). (3) People with healthy coronary artery will have decreased amplitude
      of R wave while patients with coronary stenosis have elevated amplitude of R
      wave. (4) As for the T wave, the positive CAG had no statistical significance
      between normal T wave group and TET positive group (P > 0.05); CAG results had
      statistical significance between normal T wave group and TET negative group (P <
      0.05). (5) Positive CAG results had no statistical significance between U-wave
      inversion group and TET positive group (P > 0.05); positive CAG results has
      statistical significance when TET negative group compared with U-wave inversion
      group or TET positive group (P < 0.05). TET is a relatively idea invasive
      diagnosis method for coronary disease, which can be utilized to evaluate the
      stage of CHD when integrating with the change of TET ECG.

PMID- 23546937
TI  - Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of
      alcohol-related mortality in traumatic brain injury?
AB  - Alcohol-related traumatic brain injury (TBI) is a common condition in medical and
      forensic practice, and results in high prehospital mortality. We investigated the
      mechanism of chronic alcoholism-related mortality by examining the effects of
      alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy
      adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH)
      group, EtOH-TBI group, or control groups (water group, water-TBI group). To
      establish chronic alcoholism model, rats in the EtOH group were given EtOH twice
      daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received
      a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic
      and ultrastructure changes and the numerical density of the synapses in the
      medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95)
      in the medulla oblongata was measured by ELISA. Compared with rats in the control
      group, rats in the chronic alcoholism group showed: (1) minor axonal
      degeneration; (2) a significant decrease in the numerical density of synapses (p
      < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in
      the EtOH-TBI group showed: (1) high mortality (50%, p < 0.01); (2) inhibited
      respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95
      expression (p < 0.05). Chronic alcoholism induces significant synapse loss and
      axonal impairment in the medulla oblongata and renders the brain more susceptible
      to TBI. The combined effects of chronic alcoholism and TBI induce significant
      synapse and axon impairment and result in high mortality.

PMID- 23546938
TI  - Resveratrol suppresses microcirculatory disturbance in a rat model of severe
      acute pancreatitis.
AB  - The present study sought to understand the mechanisms of attenuation of severe
      acute pancreatitis (SAP) by resveratrol (RES). SAP was experimentally induced in
      rats by injection of 4% sodium taurocholate in the retrograde pancreatic duct.
      Three study groups were evaluated: Group I (sham-operated animals), Group II (SAP
      animals), and Group III (SAP animals treated with RES at 20 mg/kg/body weight, 5
      min after induction of SAP). The study outcomes were histopathologic changes and
      alterations in biochemical markers: plasma renin activity and levels of
      angiotensin II, endothelin, and nitric oxide in plasma. Biochemical markers were
      evaluated at 3, 6, and 12 h after induction of SAP. SAP was associated with
      significant (p < 0.05) histopathologic changes (saponification spots in the
      intraperitoneal cavity, severe pancreatic edema, blood congestion, varying
      degrees of necrosis, etc.), as well as with elevation of biochemical markers in
      blood plasma. RES treatment significantly (p < 0.05) attenuated changes of both
      histopathologic and biochemical markers induced by SAP. In conclusion, this study
      provides evidence that RES treatment is a promising therapeutic approach to
      suppress microcirculatory disturbance in SAP.

PMID- 23546939
TI  - Delayed ventricular septal perforation caused by minimal branches occlusion
      during coronary artery stenting.
AB  - A 75-year-old woman was admitted to our hospital with stable effort angina
      pectoris. The coronary angiogram showed 90 % stenosis at the left anterior
      descending artery and stenting was successfully performed. Three months later, a
      newly audible systolic heart murmur was heard. Computed tomography revealed a
      ventricular septal perforation. Coronary angiogram immediately after stenting
      showed major septal branch was intact but two small septal branches were
      occluded. In the angiography after septal perforation occurred, these small
      septal branches remained occluded and stent restenosis was not observed. The
      ventricular septal perforation was presumed to be due to occlusions of minimal
      septal branches.

PMID- 23546940
TI  - A new virus-induced gene silencing vector based on Euphorbia mosaic virus-Yucatan
      peninsula for NPR1 silencing in Nicotiana benthamiana and Capsicum annuum var.
      Anaheim.
AB  - Virus-induced gene silencing is based on the sequence-specific degradation of
      RNA. Here, a gene silencing vector derived from EuMV-YP, named pEuMV-YP:DeltaAV1,
      was used to silence ChlI and NPR1 genes in Nicotiana benthamiana. The silencing
      of the ChlI transcripts was efficient in the stems, petioles and leaves as
      reflected in tissue bleaching and reduced transcript levels. The silencing was
      stable, reaching the flowers and fruits, and was observed throughout the life
      cycle of the plants. Additionally, the silencing of the NPR1 gene was efficient
      in both N. benthamiana and Capsicum annuum. After silencing, the plants' viral
      symptoms increased to levels similar to those seen in wild-type plants. These
      results suggest that NPR1 plays a role in the compatible interactions of EuMV-YP
      N. benthamiana and EuMV-C. annum var. anaheim.

PMID- 23546941
TI  - Decreased expression of the DBC2 gene and its clinicopathological significance in
      breast cancer: correlation with aberrant DNA methylation.
AB  - Loss of DBC2 (deleted in breast cancer 2) gene expression is frequent in breast
      cancer tissues. This can be explained by homozygous deletions or other mutations
      in a minority of cases but alternative mechanisms need to be investigated. Here,
      DBC2 expression was significantly suppressed compared with normal breast tissues
      in breast cancer tissues when analyzed by RT-PCR. Furthermore, DNA methylation on
      DBC2 was more prevalent in breast tumors than in normal tissues. DBC2 mRNA levels
      correlated with the degree of DBC2 methylation in breast cancer tissues and in a
      breast cancer cell line (T47D). Clinico-pathological correlation analysis showed
      that DBC2 promoter methylation was associated with tumor-node-metastasis stages
      II and III/IV, lymph node metastasis, p53 mutation, and HER2-positive status.
      Thus loss of DBC2 expression is caused by abnormal methylation of DBC2 and might
      have a role in breast cancer development. 

PMID- 23546942
TI  - Cloning, expression and characterization of a
      phosphoglucomutase/phosphomannomutase from sphingan-producing Sphingomonas
      sanxanigenens.
AB  - Several strains of the genus Sphingomonas produce sphingans, extracellular
      polysaccharides used as thickeners, emulsifiers and gelling agents. The pgmG gene
      from Sphingomonas sanxanigenens, which encodes a bifunctional protein with
      phosphoglucomutase and phosphomannomutase activities, was cloned and sequenced.
      The predicted amino acid sequence of the PgmG protein possessed 460 amino acids
      and a calculated molecular mass of 49.8 kDa, and it was 80 % identical to PGM/PMM
      from S. elodea. We overexpressed pgmG in Escherichia coli, and the purified
      protein displayed a K m of 0.2 mM and a V max of 1.3 MUmol min(-1) mg(-1) with
      glucose 1-phosphate as substrate. The catalytic efficiency (K cat/K m) of PgmG
      was about 15-fold higher for glucose 1-phosphate than for mannose 1-phosphate.
      Overexpression of pgmG in S. sanxanigenens resulted in a 17 +/- 0.3 % increase in
      sphingan production to ~12.5 g l(-1).

PMID- 23546943
TI  - Identification and characterization of a novel C20-elongase gene from the marine
      microalgae, Pavlova viridis, and its use for the reconstitution of two pathways
      of long-chain polyunsatured fatty acids biosynthesis in Saccharomyces cerevisiae.
AB  - The marine microalga, Pavlova viridis, contains long-chain polyunsatured fatty
      acids including eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid
      (DPA, 22:5n-3). A full-length cDNA sequence, pvelo5, was isolated from P.
      viridis. From sequence alignment, the gene was homologous to fatty acyl elongases
      from other organisms. Heterologous expression of pvelo5 in Saccharomyces
      cerevisiae confirmed that it encoded a specific C20-elongase within the n-3 and n
      6 pathways. Elongation activity was confined exclusively to EPA and arachidonic
      acid (20:4n-6). GC analysis indicated that pvelo5 could co-express with other
      genes for biosynthesis to reconstitute the Delta8 and Delta6 pathways. Real-time
      PCR results and fatty acid analysis demonstrated that long-chain polyunsatured
      fatty acids production by the Delta8 pathway might be more effective than that by
      the Delta6 pathway. 

PMID- 23546944
TI  - Molecular taxonomy and evolutionary hypothesis concerning Astyanax fasciatus
      (Characiformes, Characidae) from Vila Velha State Park and Tibagi and Iguacu
      Rivers.
AB  - A species complex hypothesis involving Astyanax fasciatus from southern Brazil
      was tested using 12S mtDNA sequences. Phylogenetic inferences were performed with
      maximum likelihood, maximum parsimony and Bayesian as phylogenetic methods and
      Hemigrammus bleheri as the outgroup. Besides 11 sequences from A. fasciatus, the
      data set was comprised of other partial 12S sequences including material from
      Astyanax altiparanae (two sequences) and Astyanax sp (four sequences), both from
      the Iguacu River. The hypothesis of an A. fasciatus species complex was
      reinforced given the close relationship between A. altiparanae and Astyanax sp
      observed in the Bayesian tree. Consequently, a taxonomic revision is necessary
      for these species.

PMID- 23546945
TI  - Characterization of SNPs in strawberry cultivars in China.
AB  - Single nucleotide polymorphisms (SNPs) occur at high frequencies in both plant
      and animal genomes and can provide broad genome coverage and reliable estimates
      of genetic relationships. The availability of expressed sequence tag (EST) data
      has made it feasible to discover SNPs. DNA analysis is crucial in genetic studies
      not only for strawberry breeding programs but also for characterization of
      hybrids and species. We cloned 96 EST sequences, and 116 SNPs were discovered by
      comparing 16 strawberry cultivars grown in the region of Nanjing, China. Sequence
      alignment of 6 group sequences derived from 16 sample cultivars yielded 116 SNPs,
      within a total genomic sequence length of 1755 bp. The SNPs were discovered with
      a mean frequency of one SNP per 15 bp. These SNPs were comprised of 57%
      transitions, 32.7% transversions, 8.6% InDels, and 1.7% others, based on which a
      phylogenetic tree was constructed. Among the 116 SNPs, 75% were located within
      the open reading frame (ORF), while 25% were located outside the ORF. All 16
      cultivars scattered well in dendrogram derived from the SNP data, demonstrating
      that SNPs can be a powerful tool for cultivar identification and genetic
      diversity analysis in strawberries.

PMID- 23546946
TI  - Molecular analysis and frequency of Staphylococcus aureus virulence genes
      isolated from bloodstream infections in a teaching hospital in Tianjin, China.
AB  - Staphylococcus aureus is an important cause of bloodstream infections worldwide.
      We examined the prevalence of genes that encode erythromycin ribosome methylase
      and bacterial toxins in S. aureus collected from bloodstream infections. Sixty
      different S. aureus isolates were obtained from blood cultures of patients who
      were admitted to a Teaching Hospital in Tianjin from January 2006 to August 2011.
      The susceptibility of the isolates to 16 antibiotics was tested. Methicillin
      resistant S. aureus (MRSA) was identified using the disk diffusion method with
      cefoxitin. PCR was used to detect genes that encode the staphylococcal
      enterotoxins, Panton-Valentine leukocidin, toxic shock syndrome toxin 1 and
      erythromycin ribosome methylase. Molecular analysis of the MRSA strains was done
      using pulsed-field gel electrophoresis (PFGE) and staphylococcal cassette
      chromosome mec (SCCmec) typing. The positivity rates of mecA, ermA, ermB, and
      ermC in the isolates were 13/60, 10/60, 18/60, and 18/60, respectively. Among the
      60 isolates, 30 harbored enterotoxin genes, with sea as the most frequent toxin
      gene (33%), followed by sec (15%), sed (12%), and seb (5%). The see and tst genes
      were not found in any of the isolates. The pvl gene was detected in four strains.
      Eleven MRSA isolates were of the SCCmec type III; two MRSA isolates could not be
      determined through SCCmec typing. PFGE analysis of the 13 MRSA isolates produced
      8 distinct pulsotypes. Virulence genes and erythromycin ribosome methylase genes
      were highly prevalent in these isolates. The PFGE results demonstrated that the
      MRSA spread through cloning, mainly involving SCCmec type III.

PMID- 23546947
TI  - Genetic diversity of Burkholderia (Proteobacteria) species from the Caatinga and
      Atlantic rainforest biomes in Bahia, Brazil.
AB  - The genus Burkholderia (beta-Proteobacteria) currently comprises more than 60
      species, including parasites, symbionts and free-living organisms. Several new
      species of Burkholderia have recently been described showing a great diversity of
      phenotypes. We examined the diversity of Burkholderia spp in environmental
      samples collected from Caatinga and Atlantic rainforest biomes of Bahia, Brazil.
      Legume nodules were collected from five locations, and 16S rDNA and recA genes of
      the isolated microorganisms were analyzed. Thirty-three contigs of 16S rRNA genes
      and four contigs of the recA gene related to the genus Burkholderia were
      obtained. The genetic dissimilarity of the strains ranged from 0 to 2.5% based on
      16S rDNA analysis, indicating two main branches: one distinct branch of the
      dendrogram for the B. cepacia complex and another branch that rendered three
      major groups, partially reflecting host plants and locations. A dendrogram
      designed with sequences of this research and those designed with sequences of
      Burkholderia-type strains and the first hit BLAST had similar topologies. A
      dendrogram similar to that constructed by analysis of 16S rDNA was obtained using
      sequences of the fragment of the recA gene. The 16S rDNA sequences enabled
      sufficient identification of relevant similarities and groupings amongst isolates
      and the sequences that we obtained. Only 6 of the 33 isolates analyzed via 16S
      rDNA sequencing showed high similarity with the B. cepacia complex. Thus, over
      3/4 of the isolates have potential for biotechnological applications.

PMID- 23546948
TI  - Involvement of ERK1/2 signaling in proliferation of eight liver cell types during
      hepatic regeneration in rats.
AB  - It has been well established that ERK1/2 signaling, often subdivided into nine
      types of pathways, can regulate the hepatocyte proliferative response during
      liver regeneration. However, the effect of ERK1/2 signaling on the proliferation
      of other hepatic cell types remains unclear. We isolated and purified 8 liver
      cell types at 10 time points after 2/3 hepatectomy in adult rats. For each cell
      type, mRNA expression changes for ERK1/2 signaling-involved genes were monitored
      up to 168 h, using microarrays. Real-time PCR assays were performed for array
      data verification. The expression levels of these genes varied considerably
      between different cell types. Integrating microarray results with gene synergical
      analysis, at the priming phase, activation of integrin/Grb2/Ras pathway in
      hepatocytes apparently contributed to G0/G1 transition. Two other pathways, G
      protein/EPAC/Rap1 and G-protein/PKA/Rap1, were stimulated in hepatic stellate
      cells, while RTK/PKC/Ras and RTK/Grb2/Ras were stimulated in Kupffer cells. At
      the progressive phase, the ERK1/2 pathway is involved in hepatocyte replication;
      three pathways, namely Ca(2+)/PKC/Ras, RTK/Grb2/Ras and G-protein/EPAC/Rap1, were
      found to play roles in biliary epithelial cell proliferation, while RTK/PKC/Ras
      and RTK/Grb2/Ras were involved in Kupffer cell proliferation, and G
      protein/PKC/Ras in pit cell proliferation. At the terminal phase, the promotive
      effect of the ERK1/2 pathway on replication of hepatocytes, biliary epithelial
      cells, oval cells, hepatic stellate cells, Kupffer cells, and dendritic cells was
      considerably reduced, possibly due to their differentiation at the end of
      regeneration. G-protein/PKC/Ras, integrin/Grb2/Ras and G-protein/ PKA/Rap1
      pathways were active in sinusoidal endothelial cells, perhaps to aid in their
      proliferation. We conclude that ERK1/2 has a signaling role in the regulation of
      proliferation of 8 cell types during liver regeneration process.

PMID- 23546949
TI  - A novel COL7A1 mutation in a Korean patient with Hallopeau-Siemens recessive
      dystrophic epidermolysis bullosa.
AB  - Dystrophic epidermolysis bullosa (DEB) is an inherited skin fragility disorder
      that presents various clinical manifestations. DEB is characterized by separation
      of sublamina densa tissue and abnormalities in the anchoring fibrils that result
      from mutations in COL7A1 and subsequent defects in type VII collagen. A 16-month
      old boy was diagnosed with Hallopeau-Siemens recessive DEB on the basis of
      typical skin lesions composed of multiple blisters with moderately healed
      erosions, scarring on trauma-exposed body sites, including hands and feet,
      pseudosyndactyly and flexion contractures of the toes, and severely dystrophic
      nails on the right hand. Genomic DNA from the patient and parents were subjected
      to direct sequencing for the COL7A1 gene. Two heterozygous mutations were
      detected in the affected child; one novel mutation designated c.4232delC in exon
      38 and a single-base substitution (c.6573+1G>C) in intron 81. Deletion of a
      single cytosine at codon 1411 within exon 38 had produced a frameshift mutation
      that created a stop codon at codon 1427 (p.Pro1411Leufs*17). This intronic base
      substitution had led to aberrant splicing and a premature termination codon. This
      is a novel mutation of COL7A1 associated with DEB in a Korean patient, adding to
      the range of COL7A1 mutations related to DEB.

PMID- 23546950
TI  - Molecular cytogenetic characterization of the Aegilops biuncialis karyotype.
AB  - Aegilops biuncialis can be hybridized with wheat (Triticum spp) and has been used
      for wheat breeding and genetic studies. The A. biuncialis karyotype (U(b) U(b)
      M(b) M(b)) was investigated based on three A. biuncialis accessions grown in
      China. Two pairs of SAT chromosomes were identified as 1U(b) and 5U(b), with a
      karyotype formula of 2n = 4x = 28 = 14m + 10sm + 4st. Fluorescence in situ
      hybridization (FISH) and C-banding approaches were used to analyze the A.
      biuncialis accession chromosomes at the mitotic stage. Based on the C-banding and
      FISH patterns, all U(b) and M(b) chromosomes could be discriminated
      simultaneously; the three A. biuncialis accessions exhibited similar patterns,
      suggesting a common origin. The U(b) genome from A. biuncialis resembled the U
      genome in the diploid species A. umbellulata, and it may be related to the
      tetraploid species containing the U genome. The M(b) genome had some differences
      compared to the M genome in the diploid species A. comosa, and it may be related
      to the tetraploid species possessing the M genome. A generalized ideogram was
      proposed for the A. biuncialis genome, which could be useful for standardized and
      accurate identification of the A. biuncialis karyotype and chromosomes.

PMID- 23546951
TI  - Intracellular localization and association of MHC class I with porcine invariant
      chain.
AB  - The objective was to investigate the intracellular localization and association
      of pig major histocompatibility complex (MHC) class I subunits with invariant
      chain (Ii). Pig MHC class I subunit cDNAs were cloned by RT-PCR and eukaryotic
      expression plasmids of alpha and beta2m were constructed with fusions to red or
      enhanced green fluorescent protein (pDsRed2-N1-alpha, pEGFP-N1-alpha, pDsRed2-N1
      beta2m, and pEGFP-N1-beta2m). A pig Ii mutant with a deleted CLIP region (DCLIP
      Ii) was constructed by overlap extension PCR. Wild-type Ii and mutant Ii were
      cloned into pEGFP-C1 (pEGFP-C1-Ii, pEGFP-C1-DCLIP-Ii). The recombinant plasmids
      of MHC I subunits and pEGFP-C1-Ii (pEGFP-C1-DeltaCLIP-Ii) were transiently
      cotransfected into COS-7 cells with Lipofectamine 2000. Immunofluorescence
      microscopy was performed to detect expression and intracellular localization of
      Ii and MHC I subunits, and immunoprecipitation was used to analyze their
      association. Our results indicated that pig Ii associates with integrated MHC I
      subunits to form oligomers, but cannot associate with single MHC I subunits.
      Furthermore, deletion of the Ii CLIP sequence blocks association with integrated
      MHC I subunits. Thus, pig Ii cannot associate with a single MHC I molecule, the
      alpha or beta2m chain, but Ii and the integrated MHC I molecule can form
      complexes that colocalize in the endomembranes of COS-7 cells. The Ii of CLIP
      plays a key role in assembly of Ii and MHC I.

PMID- 23546952
TI  - A non-destructive genotyping system from a single seed for marker-assisted
      selection in watermelon.
AB  - Genomic tools for watermelon breeding are becoming increasingly available. A high
      throughput genotyping system would facilitate the use of DNA markers in marker
      assisted selection. DNA extraction from leaf material requires prior seed
      germination and is often time-consuming and cost prohibitive. In an effort to
      develop a more efficient system, watermelon seeds of several genotypes and
      various seed sizes were sampled by removing 1/3 or 1/2 sections from the distal
      ends for DNA extraction, while germinating the remaining proximal parts of the
      seed. Removing 1/3 of the seed from the distal end had no effect on seed
      germination percentage or seedling vigor. Different DNA extraction protocols were
      tested to identify a method that could yield DNA of sufficient quality for
      amplification by polymerase chain reaction. A sodium dodecyl sulfate extraction
      protocol with 1% polyvinylpyrrolidone yielded DNA that could be amplified with
      microsatellite primers and was free of pericarp contamination. In this study, an
      efficient, non-destructive genotyping protocol for watermelon seed was developed.

PMID- 23546953
TI  - Confirmation of a purple-leaved plum graft hybrid.
AB  - Fifty-seven scions from an adult purple-leaved plum tree were grafted onto the
      crown of a 6-year-old Yuhuang plum tree and compared to the control of a non
      grafted tree. The floral buds of the purple-leaved plum were fully removed before
      blossoming to avoid sexual hybridization between the two species. The seeds of
      the Yuhuang plum were picked in July and sown in the spring after stratification.
      Three, eleven and eight variants with purplish red leaves were found among the
      seedlings that grew from the seeds picked in 1999, 2000, and 2001, respectively.
      The ratio of variant occurrence ranged from 2.3 to 15.8%. Our results confirmed
      the observation of a graft hybrid by Luther Burbank.

PMID- 23546954
TI  - Accurate monitoring of promoter gene methylation with high-resolution melting
      polymerase chain reaction using the ABCB1 gene as a model.
AB  - Multidrug resistance is the major cause of cancer chemotherapy failure. This
      phenotype is mainly due to the overexpression of the human ABCB1 gene. Several
      studies have shown that the transcriptional regulation of this gene is complex.
      Yet, the impact of this transcriptional regulation has not been well studied in a
      clinical setting. The acquired expression of ABCB1 is associated with the genomic
      instability of cancer cells. This includes the occurrence of mutational events
      that alter chromatin structures through epigenetic modifications such as promoter
      methylation. Therefore, it is important to introduce new clinical methods to
      monitor the methylation status of ABCB1 and determine its association with gene
      expression in order to be able to predict response to therapies. The high
      resolution melting (HRM) method has emerged as a highly accurate and sensitive
      method to quantify methylation status at specific sites of DNA. Here, we
      established HRM parameters to evaluate the promoter methylation status of the
      ABCB1 gene. Our study is the first to standardize the HRM dissociation curve to
      evaluate ABCB1 gene methylation. The association between ABCB1 methylation status
      and gene expression in established cancer cell lines shows that this method is
      accurate and reliable.

PMID- 23546955
TI  - Assessment of phylogenetic relationship of rare plant species collected from
      Saudi Arabia using internal transcribed spacer sequences of nuclear ribosomal
      DNA.
AB  - The rare and endangered plants of any country are important genetic resources
      that often require urgent conservation measures. Assessment of phylogenetic
      relationships and evaluation of genetic diversity is very important prior to
      implementation of conservation strategies for saving rare and endangered plant
      species. We used internal transcribed spacer sequences of nuclear ribosomal DNA
      for the evaluation of sequence identity from the available taxa in the GenBank
      database by using the Basic Local Alignment Search Tool (BLAST). Two rare plant
      species viz, Heliotropium strigosum claded with H. pilosum (98% branch support)
      and Pancratium tortuosum claded with P. tenuifolium (61% branch support) clearly.
      However, some species, viz Scadoxus multiflorus, Commiphora myrrha and Senecio
      hadiensis showed close relationships with more than one species. We conclude that
      nuclear ribosomal internal transcribed spacer sequences are useful markers for
      phylogenetic study of these rare plant species in Saudi Arabia.

PMID- 23546956
TI  - Identification and analysis of phospholipid transfer protein polymorphisms and
      their association with marbling score in Hanwoo (Korean cattle).
AB  - Phospholipid transfer protein (PLTP) regulates high-density lipoprotein
      metabolism. The gene encoding PLTP is located on bovine chromosome 13. The
      objective of this study was to identify single nucleotide polymorphisms (SNPs) in
      the Hanwoo (Bos taurus coreanae) PLTP gene to detect novel mutations affecting
      economically important traits. Five SNPs were identified in the coding region
      (C7368T, G7453A, C9888T, and C9905T) and intron (A1750G). G7453A changes amino
      acid 362 of PLTP from alanine to threonine, and C9888T changes amino acid 491 of
      PLTP from proline to serine. Statistical analyses revealed that the G7453A and
      C9888T polymorphisms in the PLTP gene were significantly associated with marbling
      score (P < 0.05). The relationship between haplotype and economic traits was
      analyzed and found to be significantly associated with marbling score (P < 0.05).
      The results suggest that PLTP polymorphisms might be an important genetic
      influence on economic traits in Hanwoo.

PMID- 23546957
TI  - Protein interaction and microRNA network analysis in osteoarthritis meniscal
      cells.
AB  - Osteoarthritis is the most common form of arthritis among elderly adults. Herein,
      we performed protein-protein interaction (PPI) and miRNA network analysis to
      evaluate the global correlation between miRNA regulation and the PPI network in
      human osteoarthritis. Our results showed that desmoplakin (DSP), cystatin A
      (CSTA), calmodulin 1, tyrosine kinase endothelial, insulin-like growth factor 1
      (IGF-1), IGF-binding protein 7 (IGFBP7), syndecan 1 (SDC1), ephrin type-A
      receptor 4, and PDZ and LIM domain protein 1 were associated with osteoarthritis.
      Among these proteins, DSP and CSTA interaction and IGF-1, IGFBP7 and SDC1
      interaction were observed in our PPI network. Furthermore, these potential target
      proteins were also linked with individual miRNA in the network. Our findings shed
      light on the PPIs and mechanisms by which miRNA may regulate the protein
      interaction network in osteoarthritis, which might provide theoretical support
      for further studies aimed at discovering new therapeutic strategies.

PMID- 23546958
TI  - Genetic variability of watermelon accessions based on microsatellite markers.
AB  - We analyzed the genetic variability of 40 watermelon accessions collected from 8
      regions of Northeastern Brazil using microsatellite markers, in order to suggest
      strategies of conservation and utilization of genetic variability in this
      species. These accessions are not commercial cultivars. They were sampled in
      areas of traditional farmers that usually keep their own seeds for future
      plantings year after year. An UPGMA dendrogram was generated from a distance
      matrix of the Jaccard coefficient, based on 41 alleles of 13 microsatellite loci.
      Analysis of molecular variance was made by partitioning between and within
      geographical regions. The similarity coefficient between accessions ranged from
      37 to 96%; the dendrogram gave a co-phenetic value of 0.80. The among population
      genetic variability was high ( (^)phiST = 0.319). Specific clusters of accessions
      sampled in 3 regions of Maranhao were observed while the other 5 regions did not
      presented specific clusters by regions. We conclude that watermelon genetic
      variability is not uniformly dispersed in the regions analyzed, indicating that
      geographical barriers or edaphoclimatic conditions have limited open mating. We
      suggest sampling a greater number of populations, so regional species diversity
      will be better represented and preserved in the germplasm bank.

PMID- 23546959
TI  - Production of interspecific hybrids between commercial cultivars of the eggplant
      (Solanum melongena L.) and its wild relative S. torvum.
AB  - Interspecific hybrids between cultivars of eggplant (Solanum melongena L.) and
      its wild relative S. torvum, which has disease resistance and desirable traits
      for crop improvement, were obtained by cross-hybridization and embryo rescue.
      Twenty-one hybrid progenies were obtained and examined based on morphological
      traits, RAPD and ISSR markers. Five of them were confirmed to be true
      interspecific hybrids. Eighteen and 14 bands from 7 RAPD and 14 ISSR primers,
      respectively, were polymorphic and present in all five hybrid seedlings and their
      parents. The morphological characteristics of leaf margin, inflorescence type and
      spine positions of the five seedlings were intermediate to the parents. These
      interspecific hybrids had low pollen viability, probably due to abnormal meiosis.

PMID- 23546960
TI  - Serum lipid abnormalities are not associated with apoB 3' VNTR polymorphism in
      nephrotic children.
AB  - Apolipoprotein B (apoB) gene 3' variable number of tandem repeat (VNTR) is highly
      variable, and therefore can be an informative marker for associative analysis of
      lipid metabolism. This is the first report focusing on a possible association of
      apoB VNTR polymorphism with nephrotic hyperlipidemia. Genomic DNA was extracted
      from 500 children with primary nephrotic syndrome (PNS) and 500 healthy controls.
      The apoB genotype was determined by PCR analysis. Allele size distribution
      followed a unimodal curve, with the main peak at the hypervariable element 35
      (HVE35); the most prevalent genotype was HVE35/35 in both control and PNS
      children. The genotype and allele distributions of apoB variants in PNS children
      were not significantly different from controls. There was significant variation
      in serum lipid profiles among different genotypes in control children.
      Individuals with the long (L) allele exhibited significantly higher total
      cholesterol, low-density lipoprotein cholesterol (LDL-C) and apoB levels than
      those with the medium (M) or short (S) allele; consequently, M/L carriers had
      significantly higher total cholesterol, LDL-C and apoB concentrations than did
      S/S, S/M, S/L, or M/M carriers. However, in PNS children, no significant
      differences in serum lipid levels were observed among individuals with different
      genotypes and alleles of apoB 3' VNTR. We conclude that hyperlipidemia in
      nephrotic children is not associated with apoB 3' VNTR polymorphism.

PMID- 23546961
TI  - SNPs at 3'-UTR of the bovine CDIPT gene associated with Qinchuan cattle meat
      quality traits.
AB  - The CDIPT is crucial to the fatty acid metabolic pathway, intracellular signal
      transduction and energy metabolism in eukaryotic cells. We detected three SNPs at
      3'-untranslated regions (UTR), named 3'-UTR_108 A > G, 3'-UTR_448 G > A and 3'
      UTR_477 C > G, of the CDIPT gene in 618 Qinchuan cattle using PCR-RFLP and DNA
      sequencing methods. At each of the three SNPs, we found three genotypes named as
      follows: AA, AB, BB (3'-UTR_108 A > G), CC, CD, DD (3'-UTR_448 G > A) and EE, EF,
      FF (3'-UTR_477 C > G.). Based on association analysis of these SNPs with
      ultrasound measurement traits, individuals of genotype BB had a significantly
      larger loin muscle area than genotype AA. Individuals of genotype CC had
      significantly thicker back fat than individuals of genotype DD. Individuals of
      genotype EE also had significantly thicker back fat than did individuals of
      genotype FF. We conclude that these SNPs of the CDIPT gene could be used as
      molecular markers for selecting and breeding beef cattle with superior body
      traits, depending on breeding goals.

PMID- 23546962
TI  - Isolation and phylogenetic analysis of novel gamma-gliadin genes in genus
      Dasypyrum.
AB  - As the most ancient member of the wheat gluten family, the gamma-gliadin genes
      are suitable for phylogenetic analysis among wheat and related species. Species
      in the grass genus Dasypyrum have been widely used for wheat cross breeding.
      However, the genomic relationships among Dasypyrum species have been little
      studied. We isolated 22 novel gamma-gliadin gene sequences, among which 10 are
      putatively functional. The open reading frame lengths of these sequences range
      from 642 to 933 bp, and these putative proteins consist of five domains.
      Phylogenetic analyses showed that all Dasypyrum gamma-gliadin gene sequences
      clustered in a large group; D. villosum and tetraploid D. breviaristatum gamma
      gliadin gene sequences clustered in a subgroup, while diploid D. breviaristatum
      gamma-gliadin gene sequences clustered at the edge of the subgroup. All of the
      Dasypyrum gamma-gliadin gene sequences were absent in three major T cell
      stimulatory epitopes binding to HLA-DQ2/8 in celiac disease patients. Based on
      the phylogenetic analyses, we suggest that D. villosum and tetraploid D.
      breviaristatum evolved in parallel from a diploid ancestor D. breviaristatum.

PMID- 23546963
TI  - Genetic diversity among red swamp crayfish (Procambarus clarkii) populations in
      the middle and lower reaches of the Yangtze River based on AFLP markers.
AB  - The red swamp crayfish has become one of the most important freshwater
      aquaculture species in China. At present, although it is widely distributed in
      the middle and lower reaches of the Yangze River basin, little is known about its
      population genetics and geographic distribution in China. We estimated the
      genetic diversity among 6 crayfish populations from 4 lakes (Hongze Lake, Poyang
      Lake, Dongting Lake, and Yue Lake) using AFLPs. A total of 129 loci were
      generated with 5 EcoRI-MseI primer combinations and scored as binary data in 139
      individuals. These data were analyzed by cluster methods with the NTSYSpc
      software package. The 6 populations were separated into 3 major clusters by
      principal coordinate analysis and cluster analysis. Among the 6 populations, the
      highest gene diversity was found within the Nanjing population. Analysis of
      molecular variance demonstrated that most variation occurred within populations
      (91.20%). The estimated average GST value across all loci was 0.4186, suggesting
      (very) low gene flow among the different localities. We conclude that there is
      high genetic differentiation among crayfish in the middle and lower reaches of
      the Yangze River. This information will help in the selection of high-quality
      individuals for artificial reproduction.

PMID- 23546964
TI  - Frequency of MDR1 single nucleotide polymorphisms in a Jordanian population,
      including a novel variant.
AB  - The multidrug resistance gene (MDR1 or ABCB1) codes for P-glycoprotein, which
      plays an important role in regulating absorption, distribution, and elimination
      of drugs. We examined MDR1 gene variants in 100 unrelated subjects from various
      regions of Jordan. The MDR1 gene was scanned using direct sequencing. Six rare
      variants in MDR1 were detected, including a new variant, T3075A. This variant did
      not affect the protein sequence (synonym for threonine). Among the common SNPs,
      the frequencies of rs1128503 (C1236T) genotypes were: 0.23 (CC), 0.41 (CT) and
      0.36 (TT). For the rs2032582 (G2677T) SNP, genotype frequencies were 0.38 for GG,
      0.45 for GT, 0.13 for TT, 0.03 for GA, and 0.01 for TA, whereas for rs1045642
      (C3435T), genotype frequencies were 0.17 for CC, 0.5 for CT and 0.33 for TT. The
      observed distribution of the common variants in the Jordanian population was
      within the range detected in other populations. These data on MDR1 gene variants
      in the Jordanian population will be useful for investigations on response to P
      glycoprotein substrate drugs.

PMID- 23546965
TI  - Promoter methylation negatively correlated with mRNA expression but not tissue
      differential expression after heat stress.
AB  - DNA methylation plays a central role in gene expression. In this study, we
      detected the promoter methylation pattern of the chicken heat shock protein 70
      (HSP70) gene and its association with messenger RNA (mRNA) expression before and
      after heat shock. The results showed that mRNA expression increased in response
      to heat stress and peaked at 3 h before dropping. Hypomethylation of the HSP70
      promoter occurred in all of the groups studied, but the difference between groups
      within tissue type was not significant. The DNA methylation level of the control
      and the 6-h treatment groups was slightly higher than that of the 3-h treatment
      group in brain tissue and leg muscle. Correlation analysis between mRNA
      expression and DNA methylation of HSP70 showed that DNA methylation was
      negatively associated with mRNA expression in leg muscle (P = 0.0124), indicating
      that DNA methylation may be negatively associated with the expression of HSP70,
      although the difference was not significant. We concluded that the expression of
      HSP70 is heat inducible and tissue dependent and that heat induction may
      correlate with DNA methylation pattern in the HSP70 promoter, whereas tissue
      dependence is unrelated to DNA methylation pattern.

PMID- 23546966
TI  - Effect of IL-18 gene promoter polymorphisms on prostate cancer occurrence and
      prognosis in Han Chinese population.
AB  - Interleukin-18 (IL-18) has been implicated in a wide variety of cellular
      functions that affect the biological response to tumors. However, there is
      insufficient evidence to prove that IL-18 gene variants are associated with risk
      of prostate cancer. We examined a possible association between two promoter
      polymorphisms, -137G/C (rs187238) and -607C/A (rs1946518), in the IL-18 gene and
      prostate cancer occurrence and prognosis in Han Chinese. We used a high
      resolution melting method to genotype these two polymorphisms in 375 Chinese Han
      patients with prostate cancer and in 400 age-matched healthy controls. A hundred
      and eighty-one prostate cancer patients who had been receiving androgen
      deprivation therapy, including operational and medical castration, were enrolled
      to follow-up in this study. Carriers of the GG genotype of the -137G/ C
      polymorphism had a 2.165-times higher risk of prostate cancer progression than
      carriers of GC [95% confidence interval (CI) = 1.270-3.687]. Patients with the GG
      genotype at clinical stages III and IV also had significantly lower rates of
      progression-free survival (relative risk = 2.174, 95%CI = 1.211-3.906). However,
      we found no significant association of genotype or allele distributions of these
      two polymorphisms with occurrence of prostate cancer. We conclude that there is
      evidence that the IL-18 gene promoter polymorphism -137G/ C influences the
      prognosis of prostate cancer patients in androgen deprivation therapy, although
      neither of the two SNPs contributes to prostate cancer development.

PMID- 23546967
TI  - Mitochondrial DNA variability in populations of Centris aenea (Hymenoptera,
      Apidae), a crop-pollinating bee in Brazil.
AB  - Centris spp are oil-collecting solitary bees that are valuable pollinators of
      crops such as Brazil nut, cashew, and acerola. We investigated the genetic
      variability of populations of C. aenea in the northeastern region of Brazil.
      Total DNA was extracted from 59 individuals from 6 locations in the States of
      Pernambuco and Bahia and a 600-650-bp fragment of the mitochondrial COI/COII
      region amplified by PCR, followed by digestion with the restriction enzymes DraI
      and SspI. PCR-RFLP analysis revealed eight different haplotypes among the
      populations. Haplotype A1, revealed by DraI, was the most frequent (50%), and
      haplotypes A3 and A4 were exclusive to Feira de Santana, Bahia and Morro do
      Chapeu, Bahia, respectively. Among the haplotypes revealed by SspI, B2 was the
      most frequent (37%) and B3 was exclusive to Feira de Santana. This information
      revealing high haplotype diversity will be useful for developing management
      strategies for Centris, especially because of increasing interest in the rearing
      and/ or relocation of these bees for crop pollination.

PMID- 23546969
TI  - Same faces, different labels: generating the cross-race effect in face memory
      with social category information.
AB  - Recognition of own-race faces is superior to recognition of other-race faces. In
      the present experiments, we explored the role of top-down social information in
      the encoding and recognition of racially ambiguous faces. Hispanic and African
      American participants studied and were tested on computer-generated ambiguous
      race faces (composed of 50 % Hispanic and 50 % African American features; MacLin
      & Malpass, Psychology, Public Policy, and Law 7:98-118, 2001). In Experiment 1,
      the faces were randomly assigned to two study blocks. In each block, a group
      label was provided that indicated that those faces belonged to African American
      or to Hispanic individuals. Both participant groups exhibited superior memory for
      faces studied in the block with their own-race label. In Experiment 2, the faces
      were studied in a single block with no labels, but tested in two blocks in which
      labels were provided. Recognition performance was not influenced by the labeled
      race at test. Taken together, these results confirm the claim that purely top
      down information can yield the well-documented cross-race effect in recognition,
      and additionally they suggest that the bias takes place at encoding rather than
      testing. 

PMID- 23546968
TI  - Molecular response of human cervical and lumbar nucleus pulposus cells from
      degenerated discs following cytokine treatment.
AB  - We investigated the molecular response of degenerated human cervical and lumbar
      nucleus pulposus (NP) cells following cytokine treatment. Degenerated cervical
      and lumbar discs (8 each) were obtained from patients who underwent discectomy
      for degenerative disc disease; NP cells were isolated and cultured. The mRNA
      expressions of aggrecan, alkaline phosphatase, type I collagen, type II collagen,
      osteocalcin, and Sox9 in the 2 groups were compared by real-time PCR, before and
      following treatment with rhBMP-2 and TGF-beta1. Immunoreactivity was analyzed to
      check protein activity. Type I collagen expression was significantly higher in
      cervical compared with that in lumbar disc cells. The mRNA expression was
      significantly increased after rhBMP-2 and TGF-beta1 treatment. After rhBMP-2
      treatment, mRNA expression of type I and II collagens increased significantly
      more in cervical than in lumbar NP cells. Following TGF-beta1 treatment, the
      increase in mRNA expression was not significantly different between cervical and
      lumbar disc cells. Protein immunoreactivity, before and after cytokine treatment
      was similar to mRNA expression data. The matrix-related gene expression of
      cervical and lumbar NP after rhBMP-2 and TGF-beta1 treatment increased similarly,
      with the exception of collagen expression.

PMID- 23546970
TI  - Recycling of superfine resolution agarose gel.
AB  - Genetic markers are now routinely used in a wide range of applications, from
      forensic DNA analysis to marker-assisted plant and animal breeding. The usual
      practice in such work is to extract the DNA, prime the markers of interest, and
      sift them out by electrically driving them through an appropriate matrix, usually
      a gel. The gels, made from polyacrylamide or agarose, are of high cost, limiting
      their greater applications in molecular marker work, especially in developing
      countries where such technology has great potential. Trials using superfine
      resolution (SFR) agarose for SSR marker screening showed that it is capable of
      resolving SSR loci and can be reused up to 14 times, thus greatly reducing the
      cost of each gel run. Furthermore, for certain applications, low concentrations
      of agarose sufficed and switching to lithium borate buffer, instead of the
      conventional Tris-borate-ethylenediaminetetraacetic acid buffer, will further
      save time and cost. The 2.5% gel was prepared following the Agarose SFR(TM)
      manual by adding 2.5 g agarose powder into 100 mL 1X lithium borate buffer in a
      250-mL flask with rapid stirring. Two midigels (105 x 83 mm, 17 wells) or 4
      minigels (50 x 83 mm, 8 wells), 4 mm thickness can be prepared from 100 mL gel
      solution. A total of 1680 PCR products amplified using 140 SSR markers from oil
      palm DNA samples were tested in this study using SFR recycled gel. As average,
      the gel can be recycled 8 times with good resolution, but can be recycled up to
      14 times before the resolutions get blurred. 

PMID- 23546971
TI  - Phylogenetic analyses of the hemagglutinin gene of wild-type strains of canine
      distemper virus in southern Brazil.
AB  - This study examined the phylogenetic relationship of strains of canine distemper
      virus (CDV) collected from Parana State, Brazil, based on the hemagglutinin gene.
      Urine samples were collected from 4 dogs from northern Parana State that
      demonstrated clinical manifestations of canine distemper. The participation of
      CDV was initially confirmed by RT-PCR targeting the nucleocapsid protein, after
      which the complete hemagglutinin gene was sequenced from each sample. Sequences
      were deposited in and compared with those already in GenBank. Phylogenetic
      analyses, using amino acid and nucleotide sequences based on the hemagglutinin
      gene, demonstrated that these strains of CDV are closely related to those from
      the Europe 1 lineage of CDV, with marked differences from other recognized
      geographical clusters of CDV isolates and from the vaccine strains. The strains
      of CDV from this region of southern Brazil appear to be related to those from
      Europe 1. 

PMID- 23546972
TI  - Comparative genome-wide gene expression analysis of rheumatoid arthritis and
      osteoarthritis.
AB  - Both rheumatoid arthritis (RA) and osteoarthritis (OA) are complex diseases.
      Studies and treatment of RA and OA have mainly focused on individual factors.
      However, there is still no clear understanding of their causes and adequate
      treatment alternatives are still being sought. We applied gene set-enrichment
      analysis to microarray datasets of RA and OA to look for regulatory mechanisms.
      We found 32 highly significant pathways, including 18 downregulated and 14
      upregulated pathways associated with RA. We also identified 18 highly significant
      pathways, including 7 downregulated and 11 up-regulated pathways associated with
      OA. Several such pathways were found in both RA and OA, including an upregulated
      PPAR signaling pathway and downregulated leukocyte transendothelial migration.
      Regulatory mechanisms in RA seem to be more complex than in OA. This information
      could be useful for diagnosis and treatment of these two diseases. 

PMID- 23546973
TI  - Genetic relationships between Lolium (Poaceae) species revealed by RAPD markers.
AB  - The genus Lolium is one of the most important groupings of temperate forage
      grasses, including about eight recognized species that are native to some
      temperate and subtropical regions of the northern hemisphere. We examined genetic
      relationships among 18 accessions representing all Lolium species using RAPD
      markers. Among 50 random primers that we screened, 13 gave reproducible
      amplification banding patterns. Each of these 13 primers generated 19-43 scorable
      fragments. A total of 367 RAPD fragments were detected, of which 95.9% were
      polymorphic across all the Lolium accessions. Dice's coefficient of dissimilarity
      ranged from 0.016 to 0.622, which is indicative of substantial genetic variations
      in these Lolium accessions. A neighbor-joining cluster analysis, with bootstrap
      permutation, produced an unrooted dendrogram, which grouped 18 accessions into
      two main clades, supporting high bootstrap values (98 and 96%). The first clade
      included the self-pollinated species, L. persicum, L. temulentum, L. remotum, and
      L. subulatum. The cross-pollinated species, i.e., L. multiflorum, L. perenne, L.
      rigidum, and L. canariense, composed the second clade, in which L. canariense
      formed a distinct subclade, indicating its higher genetic separation from other
      allogamous species. The value of r = 0.97 in the Mantel test for cophenetic
      correlation applied to the cluster analysis indicated the high degree of fit of
      the accessions to a group. A principal coordinate analysis, whose first three
      coordinates explained 72.6% of the variation, showed similar groupings as in the
      cluster analysis. The genetic relationships estimated by the polymorphism of RAPD
      markers are basically in agreement with those previously inferred with other
      genetic markers.

PMID- 23546974
TI  - Prevalence of variants that confer risk for venous thromboembolism in an elderly
      population of northeastern Brazil.
AB  - Venous thromboembolism (VTE) is an important cause of morbidity and mortality
      stemming from cardiovascular disease. It is a multifactorial disease caused by a
      combination of acquired risk factors, of which advanced age is the most
      significant, and genetic factors, including the variants FV G1691A, FII G20210A,
      and MTHFR C677T. We estimated the prevalence of these genomic variants in an
      elderly population of northeastern Brazil. The study included 188 elderly persons
      (65-93 years), of which 68 (36.2%) were men and 120 (63.8%) were women. Variants
      were detected by polymerase chain reaction-restriction fragment length
      polymorphism analysis, and subsequent electrophoresis on an 8% polyacrylamide gel
      stained with silver nitrate. The study population was in Hardy-Weinberg
      equilibrium for the 3 loci. Of the individuals analyzed, none carried variants of
      FV or FII (0%), and 24.7% had the MTHFR C677T polymorphism: 59 subjects (31.4%)
      were heterozygous (CT) and 17 subjects (9%) were homozygous (TT). Based on the
      analysis of these particular genes, we conclude that the study population does
      not present an increased risk for the development of VTE. Faced with a growing
      aging population worldwide, similar studies in other countries will help in the
      prevention of VTE in older individuals. 

PMID- 23546976
TI  - Genetic diversity of gabiroba based on random amplified polymorphic DNA markers
      and morphological characteristics.
AB  - The fragmentation of the original vegetation of the Cerrado biome, caused by the
      expansion of agricultural areas, mainly in central-west Brazil, calls for an
      assessment of the native population of this vegetation, especially of the species
      of interest for domestication and sustainable use. The purpose of this study was
      to characterize the genetic diversity of 140 gabiroba mother plants (Campomanesia
      spp) and their progenies from 17 locations in Goias. The morphological
      characteristics of the mother plants were evaluated, and the leaflets were
      collected for molecular analysis using 12 random amplified polymorphic DNA
      primers. The seed progenies of these matrices were transplanted to the field and
      morphologically evaluated. Distance matrices of the morphological data of the
      mother plants and progenies as well as the molecular data of the mother plants
      were constructed, and groups were formed using the Tocher method and the
      unweighted pair-group method based on arithmetic averages. The polymorphism level
      in the matrix was 90.44%. The greatest molecular distance (0.66) was observed
      between mother plants from Santa Rita do Araguaia and Alexania. By the Tocher
      method, 10, 13, and 17 groups were formed. The morphological evaluation of the
      mother plants and progenies as well as the molecular analysis of the mother
      plants showed genetic diversity. Significant genetic variability was detected in
      the progenies of the gabiroba base collection planted in Campus Jatai, Goias.

PMID- 23546975
TI  - Roles of functional NFKB1 and beta-TrCP insertion/deletion polymorphisms in mRNA
      expression and epithelial ovarian cancer susceptibility.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of death among all
      gynecological cancers. Nuclear factor-kappa B (NF-kappaB) is involved in
      carcinogenesis and in the development of EOC. The beta-transducin repeat
      containing protein (beta-TrCP) is a positive regulator of the NF-kappaB signaling
      pathway. Recent studies have indicated that the -94 ins/del ATTG polymorphism in
      the promoter region of the NFKB1 gene, and the 9N ins/del polymorphism in the 3'
      untranslated region of the beta-TrCP gene are associated with increased
      susceptibility to a variety of cancers. We examined a potential association
      between these two polymorphisms and EOC. Genotypes were determined for 187
      patients with EOC and 221 healthy control subjects, using the MassARRAY system.
      We found a significant association between the -94 ins/del ATTG genotype
      distribution and EOC. The frequency of the -94 del ATTG allele was significantly
      lower in EOC patients compared to healthy controls. The NF-kappaB mRNA level in
      cancer tissue was significantly correlated with -94 ins/del ATTG genotypes.
      Compared to the ATTG1/ATTG1 phenotype, the NF-kappaB mRNA level was 2.089 and
      1.257 times higher in the ATTG2 (insertion)/ATTG2 homozygote and the ATTG1
      (deletion)/ATTG2 heterozygote, respectively. However, we found no evidence of
      association between the 9N ins/del polymorphism of the beta-TrCP gene and EOC in
      this Chinese population. Based on these results, we suggest that the NF-kappaB 
      94 ins/del ATTG polymorphism is a risk factor for EOC susceptibility.

PMID- 23546977
TI  - Use of morpho-agronomic traits and DNA profiling for classification of genetic
      diversity in papaya.
AB  - We examined the genetic diversity of papaya (Carica papaya) based on morpho
      agronomic and molecular data. Twenty-seven genotypes grown in Brazil were
      analyzed with 11 AFLP primer combinations, 23 ISSR markers, 22 qualitative, and
      30 quantitative descriptors. For the joint analyses, we used the Gower algorithm
      (Joint Gower) and the average value of the individual dissimilarity matrix for
      each type of data (Average-Joint Gower); 359 AFLP and 52 ISSR polymorphic bands
      were found. Approximately 29.2 and 7.7% of the AFLP and ISSR bands, respectively,
      were genotype-specific and may therefore be used for papaya variety protection.
      Although there was a significant correlation between the qualitative and
      quantitative descriptor dissimilarity matrices (r = 0.43), the morpho-agronomic
      data were not highly correlated with the molecular data. Moreover, correlation
      between AFLP and ISSR dissimilarity matrices was nearly null (r = -0.01). Joint
      Gower analysis of all data showed high correlations, especially for AFLP markers,
      most likely due to the larger number of bands, generating a strong bias in the
      diversity estimates. The Average-Joint Gower analysis allowed a better balance
      between the correlations for the continuous and the discrete variables. The
      results generated by clustering analysis distinguished 5 genetically distinct
      groups. While we found that papaya genotypes are significantly variable for many
      traits, we observed that Average-Joint Gower analysis allowed for genotype
      clustering based on the most widely used criterion for classifying papaya
      genotypes, which is fruit type ('Formosa' or 'Solo'). This information helps
      provide an accurate estimate of the genetic diversity and structure of papaya
      germplasm, which will be used for further breeding strategies. 

PMID- 23546978
TI  - Conservation genetics of Annamocarya sinensis (Dode) Leroy, an endangered endemic
      species.
AB  - The endangered perennial plant Annamocarya sinensis (Dode) Leroy is a tertiary
      relict tree restricted to southeastern China and northern Vietnam. To explore
      endangerment mechanisms, develop protection strategies, and guide reintroduction
      efforts for this species, we investigated genetic diversity and population
      structure by surveying 70 individuals from three distinct populations using 12
      polymorphic microsatellite markers. We found high genetic diversity for A.
      sinensis as indicated by high allelic diversity (allelic number = 4.667 +/-
      0.436, effective number of alleles = 2.913 +/- 0.249), excess heterozygosity
      (observed heterozygosity = 0.586 +/- 0.039, expected heterozygosity = 0.582 +/-
      0.029), and low fixation index (-0.028 +/- 0.057). Our research revealed low
      genetic differentiation (FST = 0.066 +/- 0.011) and no correlation between
      genetic distance and geographic distance. Analysis of molecular variance
      attributed 87% of the variance to differences within the population, whereas 13%
      was distributed among populations. The protection strategy should aim to protect
      as many populations as possible. Promoting sexual reproduction among various
      genotypes and establishing an outcrossing program are advisable for A. sinensis. 

PMID- 23546979
TI  - Genetic diversity of natural populations of Machilus thunbergii, an endangered
      tree species in eastern China, determined with ISSR analysis.
AB  - The genetic diversity of 10 Machilus thunbergii populations in eastern China was
      analyzed using inter-simple sequence repeat markers. The populations showed high
      genetic diversity, with an overall population genetic diversity of 0.2343.
      Genetic diversity varied largely among populations, and populations with the
      highest genetic diversity were mainly from the eastern and western parts of the
      natural distribution area. Small populations, lack of effective gene flow, and
      fragmentation of habitats have led to greater genetic differentiation among
      populations, with 41.18% of genetic variation existing among populations.
      Unweighted pair-group method with arithmetic mean cluster analysis indicated that
      populations distributed between latitudes 25 degrees  and 31 degrees N were
      clustered together and should be prioritized for in situ conservation. Northern,
      eastern, and southern populations were located in peripheral areas of the
      distribution range and were clustered separately. Collection of distinctive
      germplasm from peripheral populations should be promoted and ex situ conservation
      of elite germplasm should be implemented. 

PMID- 23546980
TI  - Regulation network analysis of testicular seminoma at various stages of
      progression.
AB  - Testicular seminoma has become the most common solid malignancy in young men,
      especially in the 20s group. We obtained the gene expression profile of human
      testicular seminoma cells from NCBI, identified the differentially expressed
      genes of testicular seminoma cells of different stages, and constructed the
      regulation networks of different stages of testicular seminoma using
      bioinformatics methodology. Forty differentially expressed genes of testicular
      seminoma cells of different stages were identified. These genes and pathways are
      apparently involved in the progression of testicular seminoma. 

PMID- 23546981
TI  - Denaturing gradient gel electrophoresis analysis of 16S ribosomal DNA to monitor
      changes in mouse gut bacterial communities during Salmonella enterica serovar
      Enteritidis latent infection.
AB  - Changes in intestinal microbial flora during a 4-week period of Salmonella
      enterica serovar Enteritidis colonization in resistant mice (latent carrier
      animals) were evaluated using a culture independent method involving denaturing
      gradient gel electrophoresis. The contents of the ileocecal portion of the
      intestines produced 26 bands. Fifty-seven percent of the bands were expressed in
      more than 80% of the samples. Forty percent of the bands present in the negative
      control were common to all samples, and 60% differed from those obtained 12 h and
      1, 5, 10, and 28 days post-inoculation (PI). A dendrogram distinguished the
      negative control as the external group, and 2 clusters were formed with 76%
      similarity, separating the 12-h PI and 3-day PI time points from the others.
      These groupings were also revealed through multivariate analysis in a principal
      component analysis and the Venn diagram. The production of interferon gamma 12 h
      and 3 days PI may explain this brief imbalance in microbiota that was quickly
      reversed in the subsequent days. These findings demonstrate that S. enterica
      serovar Enteritidis can colonize the gut and persist in balance with the
      microbiota of resistant hosts. 

PMID- 23546982
TI  - Isolation and characterization of polymorphic DNA microsatellite loci for
      Anopheles triannulatus sensu lato (Diptera: Culicidae) and cross-amplification in
      congeneric species.
AB  - Anopheles (Nyssorhynchus) triannulatus is a complex of 3 species. Thirteen
      polymorphic microsatellite loci were isolated and characterized in 20 to 25
      individuals from Manaus (AM, Brazil). The number of alleles per locus varied from
      3 to 10 (mean = 6.0). The observed heterozygosity ranged from 0.250 to 0.875
      (mean = 0.680) and expected heterozygosity ranged from 0.376 to 0.844 (mean =
      0.698). Two loci exhibited null alleles and all loci were in Hardy-Weinberg
      equilibrium. No linkage disequilibrium between loci was observed. These loci were
      used in 4 congeneric species and provide a useful tool for studying population
      genetics and other aspects of the biology of this and other Anopheles species.

PMID- 23546983
TI  - Genetic diversity studies in pea (Pisum sativum L.) using simple sequence repeat
      markers.
AB  - The genetic diversity among 28 pea (Pisum sativum L.) genotypes was analyzed
      using 32 simple sequence repeat markers. A total of 44 polymorphic bands, with an
      average of 2.1 bands per primer, were obtained. The polymorphism information
      content ranged from 0.657 to 0.309 with an average of 0.493. The variation in
      genetic diversity among these cultivars ranged from 0.11 to 0.73. Cluster
      analysis based on Jaccard's similarity coefficient using the unweighted pair
      group method with arithmetic mean (UPGMA) revealed 2 distinct clusters, I and II,
      comprising 6 and 22 genotypes, respectively. Cluster II was further
      differentiated into 2 subclusters, IIA and IIB, with 12 and 10 genotypes,
      respectively. Principal component (PC) analysis revealed results similar to those
      of UPGMA. The first, second, and third PCs contributed 21.6, 16.1, and 14.0% of
      the variation, respectively; cumulative variation of the first 3 PCs was 51.7%.

PMID- 23546984
TI  - Effect of chromosome constitution variations on the expression of Turner
      phenotype.
AB  - Turner syndrome (TS) is a chronic disease related to haploinsufficiency of genes
      that are normally expressed in both X chromosomes in patients with female
      phenotype that is associated with a wide range of somatic malformations. We made
      detailed cytogenetic and clinical analysis of 65 patients with TS from the region
      of Recife, Brazil, to determine the effects of different chromosome constitutions
      on expression of the TS phenotype. Overall, patients with X-monosomy exhibited a
      tendency to have more severe phenotypes with higher morbidity, showing its
      importance in TS prognosis. Additionally, we found rare genetic and phenotypic
      abnormalities associated with this syndrome. To the best of our knowledge, this
      is the first case of 45,X,t(11;12)(q22;q22) described as a TS karyotype. Turner
      patients usually have normal intelligence; however, moderate to severe levels of
      mental retardation were found in 5 TS cases, which is considerate a very uncommon
      feature in this syndrome. 

PMID- 23546985
TI  - Meta-analysis demonstrates lack of a relationship between XRCC1-399 gene
      polymorphisms and susceptibility to hepatocellular carcinoma.
AB  - XRCC1-399 allele polymorphisms have been reported to be associated with
      susceptibility to hepatocellular carcinoma (HCC), but the conclusions of the
      various studies have been inconsistent. We conducted a meta-analysis of available
      studies to determine whether XRCC1-399 alleles influence susceptibility to
      hepatocellular carcinoma. We searched English-language databases, including
      PubMed, Medline and Embase, using terms such as "hepatocellular carcinoma" (or
      "HCC"), "X-ray repair cross-complementing group 1" (or "XRCC1") and "genetic
      polymorphism" (or "SNP"), among others; we also searched Chinese-language
      databases, including CNKI, VIP, Wanfang Data, and CBM, using terms such as
      "ganai", "ganxibaoai", "ganzhongliu", "duotaixing", and "X-xian xiufu jiaocha
      hubu jiyin 1". Eight independent studies, including 1604 HCC cases and 2185
      controls, were included. The pooled odds ratio for XRCC1-399 was 0.99 (95%
      confidence interval = 0.75-1.31). We conclude that XRCC1- 399 gene polymorphisms
      are unrelated to risk for HCC. 

PMID- 23546986
TI  - Insulin-like growth factor I gene polymorphism associated with growth and carcass
      traits in Thai synthetic chickens.
AB  - Four Thai synthetic chicken lines (Kaen Thong, Khai Mook Esarn, Soi Nin, and Soi
      Pet) originated from Thai native and exotic commercial chickens were evaluated
      for their growth and carcass traits with the purpose of developing a Thai broiler
      breeding program. Insulin-like growth factor I (IGF-I) gene is known to play an
      important role in growth, proliferation and differentiation. Consequently, we
      investigated the possibility of using the IGF-I gene for marker-assisted
      selection in Thai synthetic chickens. We looked for variations in the IGF-I gene
      and studied their association with growth and carcass traits; 1046 chickens were
      genotyped using PCR-RFLP methods. A general linear model was used to analyze
      associations of the IGF-I polymorphism with growth and carcass traits. Kaen
      Thong, Khai Mook Esarn, and Soi Nin chickens were found to carry similar
      frequencies of alleles A and C (0.40-0.60), while Soi Pet chickens had high
      frequencies of allele C (0.75). The IGF-I gene was significantly associated with
      some growth traits (body weight at hatching, and at 4, 8, 12, and 14 weeks of
      age; average daily gain during 0-12 and 0-14 weeks of age) in all synthetic
      chickens. Carcass traits (the percentage of dressing and pectoralis major) were
      significantly different only in Khai Mook Esarn chickens. We conclude that IGF-I
      can be used as a marker gene for the selection of growth and carcass traits of
      synthetic chickens in a marker-assisted selection program.

PMID- 23546987
TI  - Molecular cloning and functional analysis of MRLC2 in Tianfu, Boer, and Chengdu
      Ma goats.
AB  - To determine the molecular basis of heterosis in goats, fluorescence quantitative
      polymerase chain reaction (PCR) was performed to investigate myosin-regulatory
      light chain 2 (MRLC2) gene expression in the longissimus dorsi muscle tissues of
      the Tianfu goat and its parents, the Boer and Chengdu Ma goats. The goat MRLC2
      gene was differentially expressed in the crossbreed, and the purebred mRNA were
      isolated and identified using fluorescence quantitative reverse transcription-PCR
      (RT-PCR). The complete coding sequence of MRLC2 was obtained using the cDNA
      method, and the full-length coding sequence consisted of 513 bp encoding 172
      amino acids. The EF-hand superfamily domain of the MRLC2 protein is well
      conserved in caprine and other animals. The deduced amino acid sequence of MRLC2
      shared significant identity with MRLC2 from other mammals. Phylogenetic tree
      analysis revealed that the MRLC2 protein was closely related to MRLC2 in other
      mammals. Several predicted miRNA target sites were found in the coding sequence
      of caprine MRLC2 mRNA. Analysis by RT-PCR showed that MRLC2 mRNA was present in
      the heart, stomach, liver, spleen, lung, small intestine, kidney, leg muscle,
      abdominal muscle, and longissimus dorsi muscles. In particular, the high
      expression of MRLC2 mRNA was detected in the longissimus dorsi, leg muscle,
      abdominal muscle, stomach, and heart, but low levels of expression were also
      observed in the liver, spleen, lung, small intestine, and kidney. The expression
      of the MRLC2 gene was upregulated in the longissimus dorsi muscle of Boer and
      Tianfu goats, and it was moderately upregulated in Chengdu Ma goats.

PMID- 23546988
TI  - Rheumatoid arthritis bone fragility is associated with upregulation of IL17 and
      DKK1 gene expression.
AB  - Our aim was to compare bone gene expression in rheumatoid arthritis (RA) and
      primary osteoporosis (OP) patients. Secondary aims were to determine the
      association of gene expression of the Wnt/beta-catenin signaling pathway with
      inflammatory cytokines in the bone microenvironment and to assess the serum
      levels of Wnt/beta-catenin proteins in both groups. RA patients referred for hip
      replacement surgery were recruited. Primary OP patients were used as controls.
      Gene expression of Wnt pathway mediators, matrix proteins, and pro-inflammatory
      cytokines were analyzed in bone samples. Bone turnover markers, inflammatory
      cytokines, and Wnt mediators were measured in serum. Twenty-two patients were
      included: 10 with RA and 12 with primary OP. The expressions of Wnt10b (p =
      0.034), its co-receptor LRP6 (p = 0.041), and its negative regulator DKK1 (p =
      0.008) were upregulated in RA bone. IL17 gene expression in bone was upregulated
      in RA patients (p = 0.031) and correlated positively with Wnt10b (r = 0.810, p =
      0.015), DKK2 (r = 0.800, p = 0.010), and RANKL/OPG ratio (r = 0.762, p = 0.028).
      DKK2 (p = 0.04) was significantly decreased in RA serum compared with primary OP.
      In conclusion, bone fragility in RA patients is induced by an unbalanced bone
      microenvironment and is associated with a specific gene expression pattern,
      namely, the upregulation of IL17 and DKK1, suggesting that the modulation of
      these two pathways might prevent RA systemic bone loss.

PMID- 23546989
TI  - Diagnosis and management of immediate hypersensitivity reactions to
      cephalosporins.
AB  - Cephalosporins are one of the most commonly prescribed classes of antibiotics.
      Immediate IgE-mediated hypersensitivity reactions have been reported with use of
      a specific cephalosporin, as a cross-reaction between different cephalosporins or
      as a cross-reaction to other beta-lactam antibiotics, namely, penicillin.
      Historically, frequent reports of anaphylaxis following administration of first-
      and second-generation cephalosporins to patients with a history of penicillin
      allergy led to the belief of a high degree of allergic cross-reactivity. More
      recent evidence reveals a significantly lower risk of cross-reactivity between
      penicillins and the newer-generation cephalosporins. The current thought is that
      a shared side chain, rather than the beta-lactam ring structure, is the
      determining factor in immunologic cross-reactivity. Understanding the chemical
      structure of these agents has allowed us to identify the allergenic determinants
      for penicillin; however, the exact allergenic determinants of cephalosporins are
      less well understood. For this reason, standardized diagnostic skin testing is
      not available for cephalosporins as it is for penicillin. Nevertheless, skin
      testing to the cephalosporin in question, using a nonirritating concentration,
      provides additional information, which can further guide the work-up of a patient
      suspected of having an allergy to that drug. Together, the history and the skin
      test results can assist the allergist in the decision to recommend continued drug
      avoidance or to perform a graded challenge versus an induction of tolerance
      procedure. 

PMID- 23546990
TI  - Acrylamide biodegradation ability and plant growth-promoting properties of
      Variovorax boronicumulans CGMCC 4969.
AB  - Species of the genus Variovorax are often isolated from nitrile or amide
      containing organic compound-contaminated soil. However, there have been few
      biological characterizations of Variovorax and their contaminant-degrading
      enzymes. Previously, we reported a new soil isolate, Variovorax boronicumulans
      CGMCC 4969, and its nitrile hydratase that transforms the neonicotinoid
      insecticide thiacloprid into an amide metabolite. In this study, we showed that
      CGMCC 4969 is able to degrade acrylamide, a neurotoxicant and carcinogen in
      animals, during cell growth in a mineral salt medium as well as in its resting
      state. Resting cells rapidly hydrolyzed 600 mg/L acrylamide to acrylic acid with
      a half-life of 2.5 min. In in vitro tests, CGMCC 4969 showed plant growth
      promoting properties; it produced a siderophore, ammonia, hydrogen cyanide, and
      the phytohormone salicylic acid. Interestingly, in soil inoculated with this
      strain, 200 mg/L acrylamide was completely degraded in 4 days. Gene cloning and
      overexpression in the Escherichia coli strain Rosetta (DE3) pLysS resulted in the
      production of an aliphatic amidase of 345 amino acids that hydrolyzed acrylamide
      into acrylic acid. The amidase contained a conserved catalytic triad, Glu59, Lys
      134, and Cys166, and an "MRHGDISSS" amino acid sequence at the N-terminal region.
      Variovorax boronicumulans CGMCC 4969, which is able to use acrylamide for cell
      growth and rapidly degrade acrylamide in soil, shows promising plant growth
      promoting properties. As such, it has the potential to be developed into an
      effective Bioaugmentation strategy to promote growth of field crops in acrylamide
      contaminated soil. 

PMID- 23546991
TI  - Effect of different frequencies of repetitive transcranial magnetic stimulation
      on acquisition of chemical kindled seizures in rats.
AB  - In the current study we investigated the effect of repetitive transcranial
      magnetic stimulation (rTMS) at different frequencies on chemical kindling in
      rats. Chemical kindling was induced by injection of pentylenetetrazol (PTZ; 45
      mg/kg) at the intervals of 48 h between the injections. In the first experiment,
      effect of 0.25, 1 and 5 Hz rTMS (four trains of 4 s at motor threshold intensity)
      on kindling acquisition was investigated. In the second experiment, the stability
      of rTMS effects was checked in animals of the first experiment during a follow-up
      period of 2 weeks. Animals received a single dose of PTZ at 7th and 14th day
      after the last PTZ injection (12th injection) and their seizure parameters were
      recorded. Obtained results showed that application of rTMS at the frequencies of
      0.25 and 1 Hz had anticonvulsant effect and decreased the PTZ kindling
      acquisition. However, when applied at the frequency of 5 Hz, it had an increasing
      effect on PTZ kindling rate. During the follow-up study, the seizure severity
      increased in animals treated with 0.25 Hz rTMS (and somehow in animals treated
      with 1 Hz rTMS), but did not change in animals treated with 5 Hz rTMS compared to
      the 12th PTZ injection. Our results showed that rTMS application may have an
      anticonvulsant effect during chemical kindling acquisition at very low frequency
      (0.25 Hz) and can increase the seizure severity at high frequency (5 Hz).
      However, during follow-up, the anticonvulsant effects of rTMS may be converted to
      proconvulsive effects.

PMID- 23546992
TI  - TOMM40 polymorphisms in Italian Alzheimer's disease and frontotemporal dementia
      patients.
AB  - Chromosome 19 is one of the several prominent chromosomes related to the risk of
      developing late-onset Alzheimer's disease (LOAD) and frontotemporal lobar
      degeneration (FTLD). However, only Apolipoprotein E (APOE) has been confirmed as
      a risk factor for both disorders. The aim of this study was to investigate a set
      of polymorphisms in the translocase of the outer mitochondrial membrane 40
      (TOMM40) gene, located in close proximity to APOE, to clarify if the TOMM40 gene
      may be considered a risk factor for AD and FTLD, independently of APOE status. We
      performed a case-control study in a dataset of Italian LOAD and FTLD patients,
      analyzing the following three single-nucleotide polymorphisms (SNPs): rs157580,
      rs2075650 and rs157581. The analysis was made in 710 Italian subjects: 282 LOAD
      patients, 156 FTLD patients and 272 healthy subjects. Our results confirm the
      presence of an association between TOMM40 SNPs and LOAD in our Italian
      population, suggesting that genetic variations proximate to APOE contributes to
      the LOAD risk. Genotype and allele distribution of the TOMM40 polymorphisms
      between the FTLD group and controls did not show any statistical difference. When
      we analyzed haplotype distribution of the SNPs, taking into account the presence
      of the APOE allele, we observed a strong association between the epsilon4 allele
      and the GAC haplotype both in LOAD and FTLD patients. In contrast, this
      association did not hold for epsilon3/GAC. These results demonstrate that the
      TOMM40 gene does not have an APOE-independent role in the risk of developing LOAD
      and FTLD.

PMID- 23546993
TI  - Expert-driven label fusion in multi-atlas-based segmentation of the prostate
      using weighted atlases.
AB  - PURPOSE: Automated segmentation is required for radiotherapy treatment planning,
      and multi-atlas methods are frequently used for this purpose. The combination of
      multiple intermediate results from multi-atlas segmentation into a single
      segmentation map can be achieved by label fusion. A method that includes expert
      knowledge in the label fusion phase of multi-atlas-based segmentation was
      developed. The method was tested by application to prostate segmentation, and the
      accuracy was compared to standard techniques. METHODS: The selective and
      iterative method for performance level estimation (SIMPLE) algorithm for label
      fusion was modified with a weight map given by an expert that indicates the
      importance of each region in the evaluation of segmentation results. Voxel-based
      weights specified by an expert when performing the label fusion step in atlas
      based segmentation were introduced into the modified SIMPLE algorithm. These
      weights incorporate expert knowledge on accuracy requirements in different
      regions of a segmentation. Using this knowledge, segmentation accuracy in regions
      known to be important can be improved by sacrificing segmentation accuracy in
      less important regions. Contextual information such as the presence of vulnerable
      tissue is then used in the segmentation process. This method using weight maps to
      fine-tune the result of multi-atlas-based segmentation was tested using a set of
      146 atlas images consisting of an MR image of the lower abdomen and a prostate
      segmentation. Each image served as a target in a set of leave-one-out
      experiments. These experiments were repeated for a weight map derived from the
      clinical practice in our hospital. RESULTS: The segmentation accuracy increased 6
      % in regions that border vulnerable tissue using expert-specified voxel-based
      weight maps. This was achieved at the cost of a 4 % decrease in accuracy in less
      clinically relevant regions. CONCLUSION: The inclusion of expert knowledge in a
      multi-atlas-based segmentation procedure was shown to be feasible for prostate
      segmentation. This method allows an expert to ensure that automatic segmentation
      is most accurate in critical regions. This improved local accuracy can increase
      the practical value of automatic segmentation.

PMID- 23546994
TI  - Cloning and expression analysis of Foxl2 during the reproductive cycle in Korean
      rockfish, Sebastes schlegeli.
AB  - Foxl2 is a member of the winged helix/forkhead family of transcription factors
      and is known to regulate ovarian aromatase, which plays a crucial role in ovarian
      differentiation. To address the role of Foxl2 in gonads and brain during gonadal
      development, we isolated the full-length cDNA of Foxl2 and analyzed its
      spatiotemporal expression patterns in the viviparous teleost Korean rockfish,
      Sebastes schlegeli. Tissue distribution pattern revealed that the Foxl2 was
      detected in the liver, fat, gill, brain, and ovary, but could hardly be found in
      the testis. Reverse transcriptase PCR suggested that Foxl2 in Korean rockfish may
      involve in ovary development in the study of expression level during gonads
      development. It also revealed that the stage of highest expression level for
      Foxl2 was almost much earlier than cyp19a1a and cyp19a1b during the gonadal
      development stage in gonads and brain except for cyp19a1a in brain. Furthermore,
      the expression pattern of Foxl2 as well as aromatases may imply the role of Foxl2
      in the up-regulation of aromatases not only in the female fish but also in male. 

PMID- 23546998
TI  - Acute acalculous cholecystitis in malaria: a review of seven cases from an adult
      cohort.
AB  - PURPOSE AND METHODS: Acute acalculous cholecystitis (AAC) is an uncommon
      condition related to serious clinical conditions, such as surgery, trauma, burn
      injuries and sepsis. The diagnosis of AAC remains challenging to make, since it
      generally occurs as a secondary event in acutely ill patients with another
      disease. Imaging evaluation is crucial, and well-known criteria are accepted for
      the diagnosis. To our knowledge, only case reports of AAC related to 12 malaria
      adult patients have been published. In this series, seven cases of AAC from a
      cohort of 42 adult patients with severe imported falciparum malaria [according to
      the World Health Organization (WHO) criteria] are presented. The aim is to report
      the cases and look for malaria conditions that may affect the incidence of this
      unusual malaria complication. RESULTS: Ultrasonography revealed gallbladder with
      wall thickening in all patients, plus other(s) major criteria. Each patient
      presented five to nine WHO severe malaria criteria: all had hyperparasitaemia and
      hyperbilirubinaemia. All patients developed renal failure, six pulmonary
      oedema/acute respiratory distress syndrome (ARDS) (five were mechanically
      ventilated) and five shock. Treatment was non-operative in five patients,
      cutaneous cholecystostomy was done in two and the outcome was favourable in all.
      CONCLUSIONS: Patients with AAC have significantly more commonly five or more
      criteria of severe malaria: renal insufficiency, pulmonary oedema/ARDS,
      parasitaemia higher than 30 %, nosocomial infection and a prolonged intensive
      care unit (ICU) stay. Increased awareness for this unusual and potentially severe
      complication of malaria is needed.

PMID- 23546999
TI  - Successful ganciclovir treatment of primary cytomegalovirus infection containing
      the UL97 mutation N510S in an intestinal graft recipient.
AB  - In solid organ transplantation, human cytomegalovirus (HCMV) is considered to be
      the most important viral pathogen. We report a case of a CMV R-/D+ small
      intestine transplant recipient with a primary CMV infection on valganciclovir
      prophylaxis. Sequencing of the HCMV DNA for drug resistance-associated mutations
      revealed the UL97 mutation N510S. This mutation has been initially reported to
      confer ganciclovir resistance. Based on in vitro recombinant phenotyping, this
      assumption has recently been questioned. Switching the antiviral treatment to an
      intravenous regimen of ganciclovir eliminated HCMV DNAemia, showing the in vivo
      efficacy of ganciclovir for the UL97 mutation N510S. Hence, knowledge of drug
      efficacy is crucial for an adequate choice of antiviral medication, carefully
      balancing antiviral potency versus the risk of harmful side effects.

PMID- 23547001
TI  - Two fatty acid elongases possessing C18-Delta6/C18-Delta9/C20-Delta5 or C16
      Delta9 elongase activity in Thraustochytrium sp. ATCC 26185.
AB  - Thraustochytrids, unicellular eukaryotic marine protists, accumulate
      polyunsaturated fatty acids. Here, we report the molecular cloning and functional
      characterization of two fatty acid elongase genes (designated tselo1 and tselo2),
      which could be involved in the desaturase/elongase (standard) pathway in
      Thraustochytrium sp. ATCC 26185. TsELO1, the product of tselo1 and classified
      into a Delta6 elongase group by phylogenetic analysis, showed strong C18-Delta6
      elongase activity and relatively weak C18-Delta9 and C20-Delta5 activities when
      expressed in the budding yeast Saccharomyces cerevisiae. TsELO2, classified into
      a Delta9 elongase subgroup, showed only C16-Delta9 activity. When expressed in
      Aurantiochytrium limacinum mh0186 using a thraustochytrid-derived promoter and a
      terminator, TsELO1 exhibited almost the same specificity as expressed in the
      yeast but TsELO2 showed weak C18-Delta9 activity, in addition to its main C16
      Delta9 activity. These results suggest that TsELO1 functions not only as a C18
      Delta6 and a C20-Delta5 elongase in the main route but also as a C18-Delta9
      elongase in the alternative route of standard pathway, while TsELO2 functions
      mainly as a C16-Delta9 elongase generating vaccenic acid (C18:1n-7) in
      thraustochytrids. This is the first report describing a fatty acid elongase
      harboring C16-Delta9 activity in thraustochytrids. 

PMID- 23547002
TI  - Investigation of proteomic profiles of lamina of Ecklonia kurome (Laminariales):
      homology-based cross-species protein identification and analysis of the post
      translational processing of vanadium-dependent bromoperoxidases using MALDI
      TOF/TOF.
AB  - Proteomic profiles of the lamina of Ecklonia kurome Okamura, one of the Japanese
      dominant laminarialean kelps, were investigated by two-dimensional
      electrophoresis (2-DE) and MALDI-TOF/TOF. Due to the absence of E. kurome DNA or
      protein databases, homology-based cross-species protein identification was
      performed using a combination of three database-searching algorithms, Mascot
      peptide mass fingerprinting, Mascot MS/MS ion search, and mass spectrometry-based
      BLAST. Proteins were extracted from the lamina by an ethanol/phenol method and
      subjected to 2-DE (pI 4-7, 10 % polyacrylamide gel). More than 700 spots were
      detected in the 2-DE gel with CBB, and 93 spots (24 proteins) were successfully
      identified by MALDI-TOF/TOF and the cross-species database searching. The
      identified proteins mainly consisted of cytoplasmic carbohydrate metabolic
      enzymes, chloroplast proteins involved in photosynthesis, and haloperoxidases.
      Interestingly, vanadium-dependent bromoperoxidases (vBPO), which is thought to be
      involved in halogen uptake, synthesis of halogenated products, and detoxification
      of reactive oxygen species, were separated into at least 23 different spots. By
      comparing mass spectra, amino acid sequences predicted from tandem mass spectra
      and haloperoxidase activities of the vBPOs, we found that (1) at least two types
      of vBPOs were expressed in the lamina of E. kurome and (2) two pro-vBPOs might be
      activated by specific cleavage at N- and C-terminal regions.

PMID- 23547003
TI  - Transcriptome profiling of gill tissue in regionally bred and globally farmed
      rainbow trout strains reveals different strategies for coping with thermal
      stress.
AB  - Thermal stress can pose a major challenge to salmonid fish. A 4x44K
      oligonucleotide microarray approach was used to screen for genetically determined
      variations of a temperature stress response during acclimation in fish gills, a
      highly specialized and complex organ responsible for gas and electrolyte exchange
      as well as excretion. The comparison addressed transcriptional changes in the
      local breeding strain BORN and imported (TCO) rainbow trout after graded 2-week
      acclimation to 8 and 23  degrees C. Besides well-characterized mediators of
      thermoregulation such as genes encoding cold-inducible RNA-binding protein and
      heat shock proteins, the present microarray study suggests several new candidate
      genes commonly regulated in gills of the two trout lines. Having identified the
      differential expression of thermoregulated genes as duplicated paralogues, they
      were subsequently validated in a gill cell model. Moreover, the comparison of
      transcriptome profiles provides evidence for distinctively employed expression
      patterns. The induction of genes encoding factors of the early innate immunity in
      BORN trout upon warming contrasts with the increased expression of adaptive
      immune genes in import trout. Cold acclimation induced genes assigned to the
      functional categories "cell death" and "ion channel activity" in import trout,
      but repressed "lipid metabolism." This manuscript provides an overview of the
      genes of the multifunctional gills in rainbow trout that are mandated after
      temperature change, suggesting links between the different temperature-dependent
      pathways and gene networks. 

PMID- 23547009
TI  - Systematic validation of candidate reference genes for qRT-PCR normalization
      under iron deficiency in Arabidopsis.
AB  - A reliable result obtained by qRT-PCR highly depends on accurate transcript
      normalization using stably expressed reference genes. However, the transcript
      levels of traditional reference genes are not always stable. Also, the inaccurate
      normalization could easily lead to the false conclusions. In this report, by
      using geNorm and NormFinder algorithms, 12 candidate reference genes were
      evaluated in Arabidopsis under iron deficiency. Our results revealed that three
      novel reference genes (SAND, YLS8 and TIP41-like) were identified and validated
      as suitable reference genes for qRT-PCR normalization in both iron deprivation
      (the addition of Ferrozine to the medium) and starvation (withdrawal of iron from
      the medium) conditions. This conclusion was also confirmed by publicly available
      microarray data. In addition, when using SAND, YLS8 and TIP41-like as multiple
      reference genes, the expression patterns of FIT1 and IRT1, two iron deficiency
      marker genes, were approximately similar with that reported previously. However,
      a weaker inducible response was obtained from qRT-PCR by normalizating EF-1alpha
      alone. Together, we proposed that the combination of SAND, YLS8 and TIP41-like
      can be used for accurate normalization of gene expression in iron deficiency
      research. These results provide a valuable evidence for the importance of
      adequate reference genes in qRT-PCR normalization, insisting on the use of
      appropriate reference gene validation in all transcriptional analyses.

PMID- 23547012
TI  - Basic image analysis and manipulation in ImageJ.
AB  - Image analysis methods have been developed to provide quantitative assessment of
      microscopy data. In this unit, basic aspects of image analysis are outlined,
      including software installation, data import, image processing functions, and
      analytical tools that can be used to extract information from microscopy data
      using ImageJ. Step-by-step protocols for analyzing objects in a fluorescence
      image and extracting information from two-color tissue images collected by bright
      field microscopy are included.

PMID- 23547011
TI  - Prediction of postoperative pulmonary function: preliminary comparison of single
      breath dual-energy xenon CT with three conventional methods.
AB  - PURPOSE: To assess the use of xenon ventilation maps (Xe-images) for predicting
      postoperative pulmonary function. MATERIALS AND METHODS: After study approval by
      the institutional review board, written informed consent was obtained from 30
      patients with lung tumors who underwent pre- and postoperative spirometry,
      pulmonary perfusion SPECT and dual-energy CT (80 kV and 140 kV/Sn) after single
      breath inspiration of 35 % xenon. Xe-images were calculated by three-material
      decomposition. Sum of pixel values of the part to be resected (A) and of the
      whole lung (B) on Xe-images or lung perfusion SPECT, and volumes or the number of
      segments of the part to be resected (A) and of the whole lung (B) on Xe-images
      were enumerated, respectively. We multiplied (1 - A/B) by each preoperative value
      from spirometry for prediction. Predictions by each of the four methods were
      compared with postoperative values. RESULTS: Predicted values for vital capacity
      (VC), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) by
      the four methods regressed significantly with measured values (R (2) = 0.56-0.77,
      p < 0.001 for all). CONCLUSION: Analysis of Xe-images can predict postoperative
      VC, FVC and FEV1 with accuracy comparable to that of CT volumetry.

PMID- 23547013
TI  - DNA isolation from mammalian samples.
AB  - DNA isolation is a fundamental initial step for molecular genetic studies. Two
      quite different methodologies are described in this unit: silica spin column and
      phenol/chloroform extraction. Currently, the most commonly used technique is the
      silica-based spin column, although phenol/chloroform extraction is still widely
      used. This unit also presents basic procedures for extraction of DNA from both
      fresh tissues and formalin-fixed, paraffin-embedded (FFPE) tissue samples.

PMID- 23547010
TI  - A shift from N-glycolyl- to N-acetyl-sialic acid in the GM3 ganglioside impairs
      tumor development in mouse lymphocytic leukemia cells.
AB  - Humans, in contrast to other mammals, do not synthesize N-glycolyl-neuraminic
      acid (Neu5Gc) due to a deletion in the gene (cmah) encoding the enzyme
      responsible for this conversion, the cytidine monophospho-N-acetyl-neuraminic
      acid hydroxylase (CMP-Neu5Ac hydroxylase). The detection of considerable amounts
      of Neu5Gc-sialoconjugates, in particular gangliosides, in human malignancies
      makes these antigens attractive targets for immunotherapy, in particular with
      monoclonal antibodies (mAbs). We have previously described a GM3(Neu5Gc)
      ganglioside-specific mAb, named 14F7, with the ability to kill tumor cells in a
      complement-independent manner. Silencing the cmah gene in GM3(Neu5Gc)-expressing
      L1210 mouse lymphocytic leukemia B cells caused the abrogation of this cytotoxic
      effect. We now show that cmah-silenced L1210 cells (cmah-kd) express a high level
      of GM3(Neu5Ac) and have an impaired ability for anchorage-independent cell growth
      and tumor development in vivo. No evidences of increased immunogenicity of the
      cmah-kd cell line were found. These results provide new evidences on the role of
      GM3(Neu5Gc), or Neu5Gc-sialoconjugates in general, in tumor biology. As an
      important tool in this study, we used the humanized version (here referred to as
      7C1 mAb) of a recently described, rationally-designed mutant of 14F7 mAb that is
      able to bind to both GM3(Neu5Gc) and GM3(Neu5Ac). In contrast to its parental
      antibody, the humanized 14F7 (14F7hT) mAb, 7C1 mAb was able to kill not only
      GM3(Neu5Gc)-expressing L1210 wild type cells, but also GM3(Neu5Ac)-expressing
      cmah-kd cells, which endorses this antibody as a potential agent for cancer
      immunotherapy. 

PMID- 23547014
TI  - A detailed protocol for formaldehyde-assisted isolation of regulatory elements
      (FAIRE).
AB  - Nucleosome displacement is a key event in the regulation of gene expression in
      the eukaryotic genome. This unit details an approach called Formaldehyde-Assisted
      Isolation of Regulatory Elements (FAIRE) for isolating nucleosome-depleted
      regions. FAIRE does not rely on the use of antibodies or enzymes, and has proven
      successful in most eukaryotic cells and tissues. The set of regulatory elements
      enriched by FAIRE is similar to those identified through DNase hypersensitivity.
      The enriched fragments can be detected by quantitative PCR, tiling DNA
      microarrays, or next-generation sequencing. Although the signal-to-noise ratio is
      typically lower than that observed for DNase assays, FAIRE has high sample-to
      sample reproducibility, requires very low amounts of input material, is
      inexpensive, is amenable to high-throughput adaptations, and is a relatively
      simple procedure with a high rate of success, even for those without extensive
      experience in molecular biology protocols.

PMID- 23547015
TI  - Synthesis and labeling of RNA in vitro.
AB  - This unit discusses several methods for generating large amounts of uniformly
      labeled, end-labeled, and site-specifically labeled RNAs in vitro. The methods
      involve a number of experimental procedures, including RNA transcription, 5'
      dephosphorylation and rephosphorylation, 3' terminal nucleotide addition (via
      ligation), site-specific RNase H cleavage directed by 2'-O-methyl RNA-DNA
      chimeras, and 2-piece splint ligation. The applications of these RNA
      radiolabeling approaches are also discussed.

PMID- 23547016
TI  - Exome sequencing by targeted enrichment.
AB  - This unit describes methods for targeted enrichment of the exon-coding portions
      of the genome using Agilent SureSelect Human All Exon 50 Mb and Roche Nimblegen
      SeqCap EZ Exome platforms. Each platform targets and enriches a large overlapping
      portion of the greater human exome. The protocols here describe the biochemical
      procedures used to enrich exomic DNA with each platform, including recommended
      modifications to the manufacturers' protocols. In addition, a brief description
      of the sequencing protocol and estimation of the needed amount of sequencing for
      each platform is included. Finally, a detailed analytical pipeline for processing
      the subsequent data is described. These protocols focus specifically on human
      exome sequencing platforms, but can be applied with some modification to other
      organisms and targeted enrichment approaches.

PMID- 23547017
TI  - AhR expression is increased in hepatocellular carcinoma.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      implicated in multiple cellular processes and its expression has been shown to
      play a critical role in tumorigenesis. However, the role of AhR in tumorigenesis
      of hepatocellular carcinoma remains unclear. In the current study, we
      investigated the role of AhR in hepatocellular carcinoma tumorigenesis and
      progression by (a) measuring the expression levels of AhR in liver lesions and
      (b) assessing the correlation between AhR expression and clinicopathologic
      parameters. The tissue microarray used in this study contained hepatocellular
      carcinoma tissues (n = 94), cancer adjacent normal hepatic tissues (n = 5) and
      normal hepatic tissues (n = 5), which were immunohistochemically assessed for AhR
      expression. Significantly stronger AhR staining was observed for hepatocellular
      carcinoma tissues than for cancer adjacent normal hepatic tissues (P = 0.003) and
      normal hepatic tissues (P = 0.004). In addition, AhR expression was associated
      with T stage (P = 0.03). The results from this study suggest that an increase in
      AhR expression is associated with hepatocellular carcinoma progression and may
      have a potential role in the treatment of hepatocellular carcinoma.

PMID- 23547018
TI  - C-reactive protein measurements as a marker of the severity of chronic
      obstructive pulmonary disease exacerbations.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of
      the lungs. Acute exacerbations of COPD (AE-COPD) are a result of infectious or
      non-infectious instances. In our study, we aimed to determine whether serum C
      reactive protein (CRP) levels are predictive indicators for disease severity and
      prognosis in hospitalized patients with AE-COPD. A total of 64 patients (36
      regular ward and 28 ICU patients) were included in the study. Cases were
      identified and classified according to the Global Initiative for COPD. The first
      CRP test levels at acceptance at the ward or intensive care unit were counted in
      the study. CRP levels of patients in intensive care were significantly higher
      than those of patients in the regular ward. Mean values of CRP were detected to
      be 6.28 +/- 6.53 mg/dl in the regular ward cases and 16.9 +/- 12.03 mg/dl in the
      ICU patients (p < 0.01). The stage of COPD did not indicate a significant
      difference in terms of CRP values. Mean CRP values were found to be 16.02 +/-
      6.95 mg/dl in mortal cases and 9.76 +/- 11.09 mg/dl in survivors (p < 0.01). High
      CRP levels were considered as a prognostic parameter and indicator of severity of
      AE-COPD. Increased mortality risk was found to be associated with high CRP
      values.

PMID- 23547019
TI  - New interview and observation measures of the broader autism phenotype:
      impressions of interviewee measure.
AB  - A 20 item observational measure of social functioning, the Impression of
      Interviewee rating scale, is one of three measures devised to assess the broader
      autism phenotype. The sample studied included families containing at least two
      individuals with autism spectrum disorder; observations were undertaken by the
      researcher who interviewed the subject. An exploratory factor analysis suggested
      a single factor was most appropriate (Cronbach's alpha of 0.78). There was a
      modest but significant retest correlation of 0.42. Correlations between live
      ratings and blind consensus ratings of vignettes were high (0.93). Correlations
      with the interview measures were moderate but statistically significant. In
      conclusion, the observational scale provides a promising start but further work
      is required before general use can be recommended. 

PMID- 23547020
TI  - Intracytoplasmic morphologically selected sperm injection outcomes: the role of
      sperm preparation techniques.
AB  - PURPOSE: To compare the results of intracytoplasmic morphologically selected
      sperm injection (IMSI) between cycles in which the swim-up (SUP) or the density
      gradient centrifugation (DGC) techniques were used for sperm preparation.
      METHODS: We evaluated 70 IMSI cycles performed in women with age <= 37 years,
      undergoing IMSI as result of male factor. The couples were divided into two
      groups: DGC group (n = 26) and SUP group (n = 44). The groups were compared with
      regard to IMSI outcomes. RESULTS: There were no significant differences between
      SUP and DGC groups regarding the number of follicles, oocytes, mature oocytes,
      oocyte yield and mature oocyte rate. Fertilization rate and high-quality embryos
      rate on day 5 of development were similar between SUP and DGC groups.
      Implantation, pregnancy and miscarriage rates were not statistically different
      between SUP and DGC groups (28.8 vs 33.3 %, 46.2 vs 57.1 % and 8.3 vs 4.2 %,
      respectively). CONCLUSIONS: Both the SUP and the DGC techniques recover improved
      sperm fractions and result in similar IMSI outcomes. Further randomized trials
      analyzing both the quality of sperm through MSOME and the IMSI outcomes are
      needed to elucidate the role of sperm preparation techniques and morphology on
      IMSI outcomes.

PMID- 23547021
TI  - A German-Israeli comparison of informal and formal service use among aged 75+.
AB  - The paper focuses on filial norms and attitudes of older people about the care
      system of welfare states. It is a further investigation of the OASIS cross
      national study and examines three questions: First, what do older people in
      Israel and Germany consider to be the proper balance between the family and the
      welfare state regarding elder care? Second, what are the responsibilities of the
      family, the welfare state and other caregivers? Third, in what way do values,
      filial norms and personal resources relate to actual service use? The empirical
      data is based on information gathered from respondents living in Israel and
      Germany, aged 75+. The results of the study indicate that familial help has not
      been fully replaced by welfare state services. These findings support the
      complementary perspective. The results also show that most respondents favour a
      shared responsibility between the welfare state and the family. The findings
      indicate that familial norms are stable and strong as expressed by elders in both
      countries. The health situation is the main factor for receiving welfare services
      and familial help in Israel. In Germany the strong effect of living alone for
      receipt of welfare services underscores the influence of older adults' social and
      personal resources on actual service use. The article discusses the findings
      referring to the importance of a combined mix of the different sources of help
      for social policy implications.

PMID- 23547022
TI  - Effect of direct-to-consumer genetic tests on health behaviour and anxiety: a
      survey of consumers and potential consumers.
AB  - Direct-to-consumer (DTC) genetic tests can be purchased over the internet. Some
      companies claim to provide relative genetic risks for various diseases and thus
      encourage healthy behaviour. There are concerns that exposure to such information
      may actually discourage healthy behaviour or increase health anxiety. An online
      survey was conducted (n = 275). Respondents were composed of individuals who had
      purchased a DTC genetic test and received their results (consumers, n = 189), as
      well as individuals who were either awaiting test results or considering
      purchasing a test (potential consumers, n = 86). Consumers were asked if their
      health behaviour or health anxiety had changed after receiving their results.
      Respondents' current health behaviour and health anxiety were queried and
      compared. In total, 27.3 % of consumers claimed a change in health behaviour, all
      either positive or neutral, with no reported cessation of any existing health
      behaviour. A change in health anxiety was claimed by 24.6 % of consumers, 85.3 %
      of which were a reduction. Consumers had significantly better health behaviour
      scores than potential consumers (p = 0.02), with no significant difference in
      health anxiety. This study points towards an association between receipt of DTC
      genetic test results and increased adoption of healthy behaviours for a minority
      of consumers based on self-report, with more mixed results in relation to health
      anxiety.

PMID- 23547024
TI  - Physiology and Endocrinology Symposium: the current status of heat shock in early
      embryonic survival and reproductive efficiency.

PMID- 23547023
TI  - A closer look at the recommended criteria for disclosing genetic results:
      perspectives of medical genetic specialists, genomic researchers, and
      institutional review board chairs.
AB  - Next generation sequencing offers benefit of improved health through knowledge,
      but comes with challenges, such as inevitable incidental findings (IFs). The
      applicability of recommended criteria for disclosure of individual results when
      applied to disclosure of IFs is not well known. The purpose of this study was to
      examine how medical genetic specialists, genomic researchers, and Institutional
      Review Board (IRB) chairs perceive the importance of recommended criteria when
      applied to genetic/genomic IFs. We conducted telephone interviews with medical
      genetic specialists (genetic counselors, genetic nurses, medical geneticists,
      laboratory professionals), genomic researchers, and IRB chairs (N = 103).
      Respondents rated and discussed the importance of nine recommended criteria
      regarding disclosure of genetic/genomic IFs. Stakeholders agreed the most
      important criteria for disclosure were: (1) the IF points to a life-threatening
      condition; (2) there is a treatment; (3) individuals indicate in writing they
      wanted to be informed of IFs. Criteria rated less important were: analytic
      validity, high penetrance, association with a young age of onset and relative
      risk more than 2.0. Respondents indicated that some technical criteria were
      confusing, and in need of context. Our findings suggest that development of
      guidelines regarding management of IF include multiple stakeholders' perspectives
      and be based on a common language. 

PMID- 23547025
TI  - Joint Alpharma-Beef Species Symposium: redefining the replacement heifer
      paradigm.

PMID- 23547027
TI  - Sandhya Koushika: Building new models and communities. Interview with Caitlin
      Sedwick.

PMID- 23547028
TI  - Aneuploidy in health, disease, and aging.
AB  - Aneuploidy, an aberrant number of chromosomes, has been recognized as a feature
      of human malignancies for over a century, but compelling evidence for causality
      was largely lacking until mouse models for chromosome number instability were
      used. These in vivo studies have not only uncovered important new insights into
      the extremely complex aneuploidy-cancer relationship but also into the molecular
      mechanisms underlying proper and aberrant chromosome segregation. A series of
      diverse mouse models for the mitotic checkpoint protein BubR1 has provided
      evidence for a provocative novel link between aneuploidization and the
      development of age-related pathologies.

PMID- 23547029
TI  - Aurora A is involved in central spindle assembly through phosphorylation of Ser
      19 in P150Glued.
AB  - Knowledge of Aurora A kinase functions is limited to premetaphase events,
      particularly centrosome maturation, G2/M transition, and mitotic spindle
      assembly. The involvement of Aurora A in events after metaphase has only been
      suggested because appropriate experiments are technically difficult. We report
      here the design of the first human Aurora A kinase (as-AurA) engineered by
      chemical genetics techniques. This kinase is fully functional biochemically and
      in cells, and is rapidly and specifically inhibited by the ATP analogue 1
      Naphthyl-PP1 (1-Na-PP1). By treating cells exclusively expressing the as-AurA
      with 1-Na-PP1, we discovered that Aurora A is required for central spindle
      assembly in anaphase through phosphorylation of Ser 19 of P150Glued. This paper
      thus describes a new Aurora A function that takes place after the metaphase-to
      anaphase transition and a new powerful tool to search for and study new Aurora A
      functions.

PMID- 23547030
TI  - The BLOC-1 complex promotes endosomal maturation by recruiting the Rab5 GTPase
      activating protein Msb3.
AB  - Membrane microcompartments of the early endosomes serve as a sorting and
      signaling platform, where receptors are either recycled back to the plasma
      membrane or forwarded to the lysosome for destruction. In metazoan cells, three
      complexes, termed BLOC-1 to -3, mediate protein sorting from the early endosome
      to lysosomes and lysosome-related organelles. We now demonstrate that BLOC-1 is
      an endosomal Rab-GAP (GTPase-activating protein) adapter complex in yeast. The
      yeast BLOC-1 consisted of six subunits, which localized interdependently to the
      endosomes in a Rab5/Vps21-dependent manner. In the absence of BLOC-1 subunits,
      the balance between recycling and degradation of selected cargoes was impaired.
      Additionally, our data show that BLOC-1 is both a Vps21 effector and an adapter
      for its GAP Msb3. BLOC-1 and Msb3 interacted in vivo, and both mutants resulted
      in a redistribution of active Vps21 to the vacuole surface. We thus conclude that
      BLOC-1 controls the lifetime of active Rab5/Vps21 and thus endosomal maturation
      along the endocytic pathway.

PMID- 23547031
TI  - Binding to F-actin guides cadherin cluster assembly, stability, and movement.
AB  - The cadherin extracellular region produces intercellular adhesion clusters
      through trans- and cis-intercadherin bonds, and the intracellular region connects
      these clusters to the cytoskeleton. To elucidate the interdependence of these
      binding events, cadherin adhesion was reconstructed from the minimal number of
      structural elements. F-actin-uncoupled adhesive clusters displayed high
      instability and random motion. Their assembly required a cadherin cis-binding
      interface. Coupling these clusters with F-actin through an alpha-catenin actin
      binding domain (alphaABD) dramatically extended cluster lifetime and conferred
      direction to cluster motility. In addition, alphaABD partially lifted the
      requirement for the cis-interface for cluster assembly. Even more dramatic
      enhancement of cadherin clustering was observed if alphaABD was joined with
      cadherin through a flexible linker or if it was replaced with an actin-binding
      domain of utrophin. These data present direct evidence that binding to F-actin
      stabilizes cadherin clusters and cooperates with the cis-interface in cadherin
      clustering. Such cooperation apparently synchronizes extracellular and
      intracellular binding events in the process of adherens junction assembly.

PMID- 23547033
TI  - PathVisio-Faceted Search: an exploration tool for multi-dimensional navigation of
      large pathways.
AB  - PURPOSE: The PathVisio-Faceted Search plugin helps users explore and understand
      complex pathways by overlaying experimental data and data from webservices, such
      as Ensembl BioMart, onto diagrams drawn using formalized notations in PathVisio.
      The plugin then provides a filtering mechanism, known as a faceted search, to
      find and highlight diagram nodes (e.g. genes and proteins) of interest based on
      imported data. The tool additionally provides a flexible scripting mechanism to
      handle complex queries. AVAILABILITY: The PathVisio-Faceted Search plugin is
      compatible with PathVisio 3.0 and above. PathVisio is compatible with Windows,
      Mac OS X and Linux. The plugin, documentation, example diagrams and Groovy
      scripts are available at http://PathVisio.org/wiki/PathVisioFacetedSearchHelp.
      The plugin is free, open-source and licensed by the Apache 2.0 License.

PMID- 23547032
TI  - Global analysis of SUMO chain function reveals multiple roles in chromatin
      regulation.
AB  - Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form
      oligomeric "chains," but the biological functions of these superstructures are
      not well understood. Here, we created mutant yeast strains unable to synthesize
      SUMO chains (smt3(allR)) and subjected them to high-content microscopic
      screening, synthetic genetic array (SGA) analysis, and high-density transcript
      profiling to perform the first global analysis of SUMO chain function. This
      comprehensive assessment identified 144 proteins with altered localization or
      intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA
      transcripts (primarily consisting of stress- and nutrient-response genes) that
      displayed a >1.5-fold increase in expression levels. This information-rich
      resource strongly implicates SUMO chains in the regulation of chromatin. Indeed,
      using several different approaches, we demonstrate that SUMO chains are required
      for the maintenance of normal higher-order chromatin structure and
      transcriptional repression of environmental stress response genes in budding
      yeast.

PMID- 23547035
TI  - Arousals are frequent and associated with exacerbated blood pressure response in
      patients with primary hypertension.
AB  - BACKGROUND: Spontaneous arousals are relatively common during sleep, and induce
      hemodynamic responses. We sought to investigate the frequency and magnitude of
      blood pressure (BP) increases triggered by spontaneous arousals in patients with
      primary hypertension. METHODS: We conducted a study in which we divided 18
      nonobese, sedentary adults without sleep-disordered breathing into two groups,
      consisting of: (i) hypertensive (HT, n = 8) patients; and (ii) normotensive (NT,
      n = 10) controls. The groups were matched for age and body mass index. All
      subjects underwent full polysomnography with simultaneous monitoring of heart
      rate (HR) and beat-by-beat BP. Each subject's BP and HR were analyzed immediately
      before BP peaks triggered by spontaneous arousals during stage 2 of nonrapid eye
      movement sleep. RESULTS: The total sleep time, sleep efficiency, and sleep
      structure in the two study groups were similar. In contrast, the number of
      arousals was significantly higher in the HT than in the NT group, at 25 +/- 5 vs.
      12 +/- 3 events/h, respectively (P < 0.05). The HR of the HT and NT groups was
      similar before arousal (65 +/- 3 bpm vs. 67 +/- 3 bpm, respectively, P < 0.01)
      and increased significantly and similarly in the two groups upon arousal (to 79
      +/- 6 bpm vs. 74 +/- 4 bpm, respectively, P < 0.01). Systolic and diastolic BPs
      were significantly higher throughout sleep in the HT than in the NT group. During
      spontaneous arousals, BP increased in both groups (P < 0.05). However, the
      magnitude of the increase in systolic BP was significantly greater in the HT than
      in the NT group (22 +/- 3 mm Hg vs. 15 +/- 3 mm Hg, P < 0.05). CONCLUSIONS:
      Patients with hypertension who do not have sleep-disordered breathing have an
      increased cardiovascular burden during sleep, which may be due to the greater
      number of arousals and exacerbated systolic BP response that they experience
      during sleep. These novel findings may have cardiovascular implications in
      patients with hypertension.

PMID- 23547034
TI  - Sex differences in angiotensin-converting enzyme modulation of Ang (1-7) levels
      in normotensive WKY rats.
AB  - BACKGROUND: Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been
      reported to be greater in females than in males, although the molecular mechanism
      responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and
      neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study
      to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in
      the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin
      activity in females would result in enhanced Ang (1-7) formation as compared with
      that in males. METHODS: We measured the enzymatic activities of ACE, ACE2, and
      neprilysin in the renal cortex and medulla of 12-week-old male and female WKY
      rats. We treated additional rats with vehicle or enalapril (10 mg/kg/day in
      drinking water) for 14 days, and measured their Ang II and Ang (1-7) levels.
      RESULTS: Renal cortical activity of ACE was greater in female than in male WKY
      rats (P < 0.05), but the activity of ACE in the renal medulla was not
      significantly different in the two sexes. Renal cortical and medullary ACE2 and
      neprilysin activities were comparable in male and female WKY rats. Treatment with
      enalapril significantly decreased Ang II levels in the renal cortex and medulla
      of male and female WKY rats as compared with those in vehicle-treated controls (P
      < 0.05); enalapril did not change the plasma levels of Ang II. Cortical levels of
      Ang (1-7) were higher in vehicle-treated females than in vehicle-treated males (P
      < 0.05), and treatment with enalapril decreased Ang (1-7) levels only in females
      (P < 0.05). CONCLUSIONS: Our data supports a role for ACE in the formation of
      renal cortical Ang (1-7) in female WKY rats that is absent in males.

PMID- 23547036
TI  - Inaccuracy in determining mean arterial pressure with oscillometric blood
      pressure techniques.
AB  - OBJECTIVE: Accurate determination of MAP is important in the calibration of
      pressure waveforms for calculating central blood pressure (BP). Currently, a
      precise, individualized measurement of mean arterial pressure (MAP) can be
      obtained only with intra-arterial measurements of BP or with applanation
      tonometry. We conducted a study of whether easy-to-use oscillometric devices,
      validated for systolic and diastolic BP measurements (BHS protocol), give
      accurate determinations of MAP. METHODS: We compared measurements of MAP made
      with the WatchBP Office oscillometric monitor in 102 subjects with values of MAP
      assessed by pulse-wave analysis (PWA) (SphygmoCor). RESULTS: The mean (+/- SD)
      oscillometric MAP assessed with the WatchBP Office monitor was 97 +/- 12.5 mm Hg,
      which was equivalent to 23.6 +/- 9.1% of the pulse pressure (PP) above diastolic
      blood pressure (DBP). The MAP as assessed through PWA was 106 +/- 14.6 mm Hg (P <
      0.01), or 37.7 +/- 3.9% of the PP above DBP. In simultaneous measurements made on
      both arms with the WatchBP Office monitor we observed individual differences in
      pressure in the left vs. the right arm. CONCLUSIONS: The MAP displayed by the
      WatchBP Office monitor is too imprecise to be used for calibrations. We suggest
      that devices for measuring BP not display MAP unless their accuracy is tested.

PMID- 23547037
TI  - Socioeconomic status, psychosocial factors, race and nocturnal blood pressure
      dipping in a Hispanic cohort.
AB  - BACKGROUND: Little information is available about the relationship of
      socioeconomic status (SES) to blunted nocturnal ambulatory blood pressure (ABP)
      dipping among Hispanics and whether this relationship differs by race. We sought
      to characterize ABP nondipping and its determinants in a sample of Hispanics.
      METHODS: We enrolled 180 Hispanic participants not on antihypertensive
      medications. SES was defined by years of educational attainment. All participants
      underwent 24-hour ABP monitoring. A decrease of <10% in the ratio between average
      awake and average asleep systolic BP was considered nondipping. RESULTS: The mean
      age of the cohort was 67.1 +/- 8.7, mean educational level was 9.4 +/- 4.4 years,
      and 58.9% of the cohort was female. The cohort was comprised of 78.3% Caribbean
      Hispanics with the rest from Mexico and Central/South America; 41.4% self
      identified as white Hispanic, 34.4% self-identified as black Hispanic, and 24.4%
      did not racially self- identify. The percentage of nondippers was 57.8%.
      Educational attainment (10.5 years vs. 8.6 years; P <0.01) was significantly
      higher among dippers than nondippers. In multivariable analyses, each 1-year
      increase in education was associated with a 9% reduction in the likelihood of
      being a nondipper (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84
      0.98; P = 0.01). There were significantly greater odds of being a nondipper for
      black Hispanics than for white Hispanics (OR, 2.83, 95% CI, 1.29-6.23; P =
      0.005). Higher SES was significantly protective of nondipping in white Hispanics
      but not black Hispanics. CONCLUSIONS: These results document a substantial
      prevalence of nondipping in a cohort of predominantly normotensive Hispanics.
      Dipping status varied significantly by race. Lower SES is significantly
      associated with nondipping status, and race potentially impacts on this relation.

PMID- 23547038
TI  - Insulin resistance and the relationship between urinary Na(+)/K(+) and ambulatory
      blood pressure in a community of African ancestry.
AB  - BACKGROUND: Although groups of African descent are particularly sensitive to
      blood pressure (BP) effects of salt intake, the role of obesity and insulin
      resistance in mediating this effect is uncertain. We determined whether obesity
      or insulin resistance is independently associated with urinary Na(+)/K(+)-BP
      relationships in a community sample of African ancestry. METHODS: We measured 24
      hour urinary Na(+)/K(+), homeostasis model assessment of insulin resistance (HOMA
      IR), and nurse-derived conventional and 24-hour ambulatory BP in 331 participants
      from a South African community sample of black African descent not receiving
      treatment for hypertension. RESULTS: With adjustments for diabetes mellitus and
      the individual terms, an interaction between waist circumference and urinary
      Na(+)/K(+) was associated with day diastolic BP (P < 0.05) and an interaction
      between log HOMA-IR and urinary Na(+)/K(+) was associated with 24-hour and day
      systolic (P < 0.05) and 24-hour, day, and night diastolic (P < 0.002; P < 0.001)
      BP. The multivariable-adjusted relationship between urinary Na(+)/K(+) and night
      diastolic BP increased across tertiles of HOMA-IR (tertile 1: beta-coefficient = 
      0.79 +/- 0.47; tertile 2: beta-coefficient = 0.65 +/- 0.35; tertile 3: beta
      coefficient = 1.03 +/- 0.46; P < 0.05 tertiles 3 and 2 vs. 1). The partial
      correlation coefficients for relationships between urinary Na(+)/K(+) and 24-hour
      (partial r = 0.19; P < 0.02), day (partial r = 0.17; P < 0.05), and night
      (partial r = 0.18; P < 0.02) diastolic BP in participants with log HOMA-IR
      greater than or equal to the median were greater than those for relationships
      between urinary Na(+)/K(+) and 24-hour (partial r = -0.08; P = 0.29), day
      (partial r = -0.10; P < 0.22), and night (partial r = -0.06; P = 0.40) diastolic
      BP in participants with log HOMA-IR less than the median (comparisons of r
      values: P < 0.05). CONCLUSIONS: Insulin resistance may modify the relationship
      between salt intake, indexed by urinary Na(+)/K(+), and ambulatory BP in groups
      of African descent.

PMID- 23547042
TI  - Screening is not as simple as it may seem.

PMID- 23547043
TI  - Re: Childhood lipid screening: evidence and conflicts.

PMID- 23547044
TI  - Universal lipid screening: response regarding implications for primary care
      practice.

PMID- 23547045
TI  - Author's response. Universal lipid screening: in response to ongoing debate.

PMID- 23547046
TI  - The relationship between vitamin D status and adrenal insufficiency in critically
      ill children.
AB  - CONTEXT: Recent studies in critically ill populations have suggested both adrenal
      insufficiency (AI) and vitamin D deficiency to be associated with worse clinical
      outcome. There are multiple mechanisms through which these pleiotropic hormones
      might synergistically influence critical illness. OBJECTIVE: The aim of the study
      was to investigate potential relationships between vitamin D status, adrenal
      status, and cardiovascular dysfunction in critically ill children. DESIGN: We
      conducted a secondary analysis of data from a prospective cohort study. SETTING
      AND PATIENTS: The study was conducted on 319 children admitted to 6 Canadian
      tertiary-care pediatric intensive care units. MAIN OUTCOME MEASURES: Vitamin D
      status was determined through total 25-hydroxyvitamin D (25OHD) levels. AI was
      defined as a cortisol increment under 9 MUg/dL after low-dose cosyntropin.
      Clinically significant cardiovascular dysfunction was defined as catecholamine
      requirement during pediatric intensive care unit admission. RESULTS: Using 3
      different thresholds to define vitamin D deficiency, no association was found
      between vitamin D status and AI. Furthermore, linear regression failed to
      identify a relationship between 25OHD and baseline or post-cosyntropin cortisol.
      However, the association between AI and cardiovascular dysfunction was influenced
      by vitamin D status; compared to children with 25OHD above 30 nmol/L, AI in the
      vitamin D-deficient group was associated with significantly higher odds of
      catecholamine use (odds ratio, 5.29 vs 1.63; P = .046). CONCLUSIONS: We did not
      find evidence of a direct association between vitamin D status and critical
      illness-related AI. However, our results do suggest that vitamin D deficiency
      exacerbates the effect of AI on cardiovascular stability in critically ill
      children.

PMID- 23547047
TI  - Oral contraception vs insulin sensitization for 18 months in nonobese adolescents
      with androgen excess: posttreatment differences in C-reactive protein, intima
      media thickness, visceral adiposity, insulin sensitivity, and menstrual
      regularity.
AB  - BACKGROUND: An oral estro-progestagen is the standard medication given to
      adolescent girls with androgen excess, even when those girls are not at risk of
      pregnancy. AIM: The aim of this study was to compare on-treatment and post
      treatment effects of intervention with an oral contraceptive vs an insulin
      sensitizing treatment for androgen excess in nonobese adolescents. DESIGN: This
      was a randomized, open-label trial. STUDY POPULATION: Subjects were nonobese
      adolescent girls with hyperinsulinemic androgen excess and without risk of
      pregnancy (mean age, 16 years; body mass index, 23 kg/m2; n = 34). INTERVENTIONS:
      The effects of treatment with ethinylestradiol-cyproteroneacetate (EE-CA) vs a
      low-dose combination of pioglitazone (7.5 mg/d), flutamide (62.5 mg/d), and
      metformin (850 mg/d) (PioFluMet) for 18 months were studied. Posttreatment follow
      up was for 6 months. MAIN OUTCOME MEASURES: Androgen excess (hirsutism and acne
      scores and serum testosterone), glucose-stimulated insulinemia, circulating C
      reactive protein, carotid intima media thickness, body composition
      (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and
      menstrual regularity were measured. RESULTS: EE-CA and PioFluMet attenuated
      androgen excess similarly but had divergent, and even opposing, effects on other
      outcomes. Six months posttreatment, the PioFluMet-treated girls had a lower
      glucose-induced insulinemia, a lower C-reactive protein level, and a thinner
      intima media than the EE-CA-treated girls, and they were viscerally less adipose,
      had a higher lean mass, and were more likely to have regular cycles. CONCLUSIONS:
      The on-treatment and post-treatment effects of PioFluMet compared favorably with
      those of oral contraception in nonobese adolescents with androgen excess. The
      intervention whereby androgen excess is reduced in adolescence influences the
      post-treatment phenotype. PioFluMet-like interventions in adolescence may thus
      hold the potential to prevent part of the androgen-excess phenotype in adulthood,
      including adiposity and subfertility.

PMID- 23547049
TI  - CD44 regulates the apoptotic response and promotes disease development in chronic
      lymphocytic leukemia.
AB  - The cell-surface glycoprotein CD44 is expressed in chronic lymphocytic leukemia
      (CLL), but its functional role in this disease is poorly characterized. We
      therefore investigated the contribution of CD44 to CLL in a murine disease model,
      the Eu-TCL1 transgenic mouse, and in CLL patients. Surface CD44 increased during
      murine CLL development. CD44 expression in human CLL was induced by stimulation
      with interleukin 4/soluble CD40 ligand and by stroma cell contact. Engagement of
      CD44 by its natural ligands, hyaluronic acid or chondroitin sulfate, protected
      CLL cells from apoptosis, while anti-CD44 small interfering RNAs impaired tumor
      cell viability. Deletion of CD44 during TCL1-driven murine leukemogenesis reduced
      the tumor burden in peripheral blood and spleen and led to a prolonged overall
      survival. The leukemic cells from these CD44 knockout animals revealed lower
      levels of antiapoptotic MCL1, a higher propensity to apoptosis, and a diminished
      B-cell receptor kinase response. The inhibitory anti-CD44 antibodies IM7 and A3D8
      impaired the viability of CLL cells in suspension cultures, in stroma contact
      models, and in vivo via MCL1 reduction and by effector caspase activation. Taken
      together, CD44 expression in CLL is mediated by the tumor microenvironment. As a
      coreceptor, CD44 promotes leukemogenesis by regulating stimuli of MCL1
      expression. Moreover, CD44 can be addressed therapeutically in CLL by specific
      antibodies.

PMID- 23547048
TI  - Mineral metabolism and cortical volumetric bone mineral density in childhood
      chronic kidney disease.
AB  - CONTEXT: The relationships among cortical volumetric bone mineral density
      (CortBMD) and comprehensive measures of mineral metabolism have not been
      addressed in chronic kidney disease (CKD). OBJECTIVE: The aim of the study was to
      identify the determinants of CortBMD in childhood CKD. A secondary objective was
      to assess whether CortBMD was associated with subsequent fracture. DESIGN AND
      PARTICIPANTS: This prospective cohort study included 171 children, adolescents,
      and young adults (aged 5-21 years) with CKD stages 2-5D at enrollment and 89 1
      year later. OUTCOMES: Serum measures included vitamin D [25-hydroxyvitamin D
      (25[OH]D), 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D],
      vitamin D-binding protein, intact PTH, fibroblast growth factor 23, calcium, and
      phosphorus. Tibia quantitative computed tomography measures of CortBMD were
      expressed as sex-, race-, and age-specific Z-scores based on 675 controls.
      Multivariable linear regression identified the independent correlates of CortBMD
      Z-scores and the change in CortBMD Z-scores. RESULTS: Lower calcium (beta = .31/1
      mg/dL, P = .01) and 25(OH)D (beta = .18/10 ng/mL, P = .04) and higher PTH (beta =
      -.02/10%, P = .002) and 1,25(OH)2D (beta = -.07/10%, P < .001) were independently
      associated with lower CortBMD Z-scores at baseline. The correlations of total,
      free, and bioavailable 25(OH)D with CortBMD did not differ. Higher baseline
      1,25(OH)2D (P < .05) and greater increases in PTH (P < .001) were associated with
      greater declines in CortBMD Z-scores. Greater increases in calcium concentrations
      were associated with greater increases in CortBMD Z-scores in growing children
      (interaction P = .009). The hazard ratio for fracture was 1.75 (95% confidence
      interval 1.15-2.67; P = .009) per SD lower baseline CortBMD. CONCLUSIONS: Greater
      PTH and 1,25(OH)2D and lower calcium concentrations were independently associated
      with baseline and progressive cortical deficits in childhood CKD. Lower CortBMD Z
      score was associated with increased fracture risk.

PMID- 23547050
TI  - The shortest isoform of C/EBPbeta, liver inhibitory protein (LIP), collaborates
      with Evi1 to induce AML in a mouse BMT model.
AB  - Ecotropic viral integration site 1 (Evi1) is one of the master regulators in the
      development of acute myeloid leukemia (AML) and myelodysplastic syndrome. High
      expression of Evi1 is found in 10% of patients with AML and indicates a poor
      outcome. Several recent studies have indicated that Evi1 requires collaborative
      factors to induce AML. Therefore, the search for candidate factors that
      collaborate with Evi1 in leukemogenesis is one of the key issues in uncovering
      the mechanism of Evi1-related leukemia. Previously, we succeeded in making a
      mouse model of Evi1-related leukemia using a bone marrow transplantation (BMT)
      system. In the Evi1-induced leukemic cells, we identified frequent retroviral
      integrations near the CCAAT/enhancer-binding protein beta (C/EBPbeta) gene and
      overexpression of its protein. These findings imply that C/EBPbeta is a candidate
      gene that collaborates with Evi1 in leukemogenesis. Cotransduction of Evi1 and
      the shortest isoform of C/EBPbeta, liver inhibitory protein (LIP), induced AML
      with short latencies in a mouse BMT model. Overexpression of LIP alone also
      induced AML with longer latencies. However, excision of all 3 isoforms of
      C/EBPbeta (LAP*/LAP/LIP) did not inhibit the development of Evi1-induced
      leukemia. Therefore, isoform-specific intervention that targets LIP is required
      when we consider C/EBPbeta as a therapeutic target.

PMID- 23547051
TI  - C/EBPalpha is required for development of dendritic cell progenitors.
AB  - Dendritic cells (DCs) are master regulators of the immune system, but molecular
      regulation of early DC differentiation has been poorly understood. Here, we
      report that the transcription factor C/EBPalpha coordinates the development of
      progenitor cells required for production of multiple categories of DCs.
      C/EBPalpha was needed for differentiation from stem/progenitor cells to common DC
      progenitors (CDPs), but not for transition of CDP to mature DCs. C/EBPalpha
      deletion in mature DCs did not affect their numbers or function, suggesting that
      this transcription factor is not needed for maintenance of DCs in lymphoid
      tissues. ChIP-seq and microarrays were used to identify candidate genes regulated
      by C/EBPalpha and required for DC formation. Genes previously shown to be
      critical for DC formation were bound by C/EBPalpha, and their expression was
      decreased in the earliest hematopoietic compartments in the absence of
      C/EBPalpha. These data indicate that C/EBPalpha is important for the earliest
      stages of steady-state DC differentiation.

PMID- 23547052
TI  - Apc regulates the function of hematopoietic stem cells largely through beta
      catenin-dependent mechanisms.
AB  - Emerging evidence suggests that adenomatous polyposis coli (Apc) plays a critical
      role in the maintenance of hematopoietic stem/progenitor cells (HSCs/HPCs). The
      molecular pathways responsible for the function of Apc in HSCs/HPCs remain
      unclear. By genetic approach, we demonstrated that inactivation of beta-catenin
      rescued the exhaustion of Apc-deficient HSCs/HPCs, thereby preventing bone marrow
      failure in Apc-deficient mice. beta-catenin loss inhibited the excessive
      proliferation and apoptosis of Apc-deficient HSCs/HPCs, as well as their defects
      in myeloid and erythroid differentiation. In addition, loss of beta-catenin
      reversed the down-regulation of Cdkn1a, Cdkn1b, and Mcl1 induced by Apc ablation
      in Lin(-)Sca(+)c-Kit(+). In assays of long-term stem cell function, the HSCs with
      deficiency of both Apc and beta-catenin displayed a significantly enhanced self
      renewal capacity compared with beta-catenin-deficient and control HSCs. Our
      findings suggest that Apc regulates the survival, proliferation, and
      differentiation of HSCs/HPCs largely through a beta-catenin-mediated pathway.
      They also indicate that multiple downstream targets of Apc including beta-catenin
      may coordinately regulate HSC self-renewal.

PMID- 23547053
TI  - Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft
      versus-host disease.
AB  - Sclerotic chronic graft-versus-host disease (GVHD) can result in disability after
      allogeneic hematopoietic cell transplantation. We assessed the incidence and risk
      factors of sclerosis and its association with transplant outcomes among 977
      consecutive patients treated with systemic immunosuppression for chronic GVHD.
      Sclerosis was defined when cutaneous sclerosis, fasciitis, or joint contracture
      was first documented in the medical record. Seventy (7%) patients presented with
      sclerosis at the time of initial systemic treatment for chronic GVHD, and the
      cumulative incidence of sclerosis increased to 20% at 3 years. Factors associated
      with an increased risk of sclerosis included the use of a mobilized blood cell
      graft and a conditioning regimen with > 450 cGy total body irradiation. Factors
      associated with a decreased risk of sclerosis included the use of an HLA
      mismatched donor and a major ABO-mismatched donor. Development of sclerosis was
      associated with longer time to withdrawal of immunosuppressive treatment but not
      with risks of overall mortality, nonrelapse mortality, or recurrent malignancy.
      We found a substantial incidence of sclerosis in patients with chronic GVHD.
      Development of sclerosis can cause disability but does not affect mortality or
      recurrent malignancy in patients with chronic GVHD.

PMID- 23547055
TI  - A new pediatrics for a new century.
AB  - Is the field of pediatrics doing all that it can for the health of children? Many
      think that the field has gone off track and that we could do better. These
      articles highlight some different ways of judging the successes and failures of
      pediatrics in the United States today. The choices that we face are stark. To
      change the system, we would need to recalibrate the balance between utilitarian
      approaches to resource allocation, such as might be dictated by cost
      effectiveness analyses, and deontologic approaches that prioritize unbreakable
      commitments or promises to individuals. These changes would entail large-scale
      social engineering projects to reshape our health care system, our educational
      system, and our public health system. A failure to change, however, might
      perpetuate a system that is not doing all it can for the health of America's
      children and the society they will form.

PMID- 23547054
TI  - GSK-3alpha promotes oncogenic KRAS function in pancreatic cancer via TAK1-TAB
      stabilization and regulation of noncanonical NF-kappaB.
AB  - Mutations in KRAS drive the oncogenic phenotype in a variety of tumors of
      epithelial origin. The NF-kappaB transcription factor pathway is important for
      oncogenic RAS to transform cells and to drive tumorigenesis in animal models.
      Recently, TGF-beta-activated kinase 1 (TAK1), an upstream regulator of IkappaB
      kinase (IKK), which controls canonical NF-kappaB signaling, was shown to be
      important for chemoresistance in pancreatic cancer and for regulating KRAS-mutant
      colorectal cancer cell growth and survival. Here, we show that mutant KRAS
      upregulates glycogen synthase kinase 3alpha (GSK-3alpha), leading to its
      interaction with TAK1 to stabilize the TAK1-TAB complex to promote IKK activity.
      In addition, GSK-3alpha is required for promoting critical noncanonical NF-kappaB
      signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3
      suppresses growth of human pancreatic tumor explants, consistent with the loss of
      expression of oncogenic genes such as c-myc and TERT. These data identify GSK
      3alpha as a key downstream effector of oncogenic KRAS via its ability to
      coordinately regulate distinct NF-kappaB signaling pathways.

PMID- 23547056
TI  - "Big data" versus "big brother": on the appropriate use of large-scale data
      collections in pediatrics.
AB  - Discussions of "big data" in medicine often revolve around gene sequencing and
      biosamples. It is perhaps less recognized that administrative data in the form of
      vital records, hospital discharge abstracts, insurance claims, and other
      routinely collected data also offer the potential for using information from
      hundreds of thousands, if not millions, of people to answer important questions.
      However, the increasing ease with which such data may be used and reused has
      increased concerns about privacy and informed consent. Addressing these concerns
      without creating insurmountable barriers to the use of such data for research is
      essential if we are to avoid a "missed opportunity" in pediatrics research.

PMID- 23547057
TI  - The developmental approach to child and adult health.
AB  - Pediatricians should consider the costs and benefits of preventing rather than
      treating childhood diseases. We present an integrated developmental approach to
      child and adult health that considers the costs and benefits of interventions
      over the life cycle. We suggest policies to promote child health that are
      currently outside the boundaries of conventional pediatrics. We discuss current
      challenges to the field and suggest avenues for future research.

PMID- 23547058
TI  - From EPSDT to EHBs: the future of pediatric coverage design under government
      financed health insurance.
AB  - We review the evolution of federal financing for child health care over the past
      40 years. The Social Security Amendments of 1967 established the program of early
      and periodic screening, diagnosis and treatment (EPSDT) as a required Medicaid
      benefit. The EPSDT amendments directed agencies to cover "early and periodic"
      screening and diagnostic services to ascertain "defects" and "chronic conditions"
      in children, as well as health care and treatment needed to "correct or
      ameliorate" such defects and conditions discovered during the screening
      examinations. The 1997 enactment of the Children's Health Insurance Program
      (CHIP) shifted federal policy from the use of an early coverage standard to one
      that gives insurers much more discretion to define medical necessity and coverage
      exclusions. CHIP programs offer coverage that is narrower than the benefits
      available under Medicaid. The Affordable Care Act (ACA) requires significantly
      more classes of care to be covered than does CHIP but well below the level of
      coverage under Medicaid. Implementation of the ACA to date suggests that the US
      Department of Health and Human Services will only demand pediatric coverage
      pegged to the commercial insurance market standards, rather than Medicaid's
      unique pediatric coverage standard. Although EPSDT's emphasis on early,
      developmental, and ameliorative services might result in more comprehensive
      benefits for children, particularly those with special health needs, one might
      still describe the ACA coverage as providing a basic, minimal level of services
      from a distributive justice perspective. It may, however, vary from state to
      state. States have the authority to decide whether to use an EPSDT-style approach
      or to follow the more restrictive approach of commercial insurance plans.
      Advocacy at the state level will determine which approach different states take.

PMID- 23547060
TI  - Reforming Medicaid for medically complex children.
AB  - Children's hospitals play a central role in our child health care system. These
      hospitals face unique challenges under health care reform. They care for children
      with the most complex medical problems but often are not reimbursed for good
      preventive care, care coordination, or quality. We discuss a proposal by
      children's hospital leaders to create a network of Nationally Designated
      Children's Hospitals. These would be Centers of Excellence on which states and
      families could rely to care for a uniquely vulnerable and uniquely costly
      population of children. On a federal level, the proposal is focused on 3
      provisions: (1) creating and delivering a national coordinated delivery model for
      children with chronic and complex conditions in Medicaid and the State Child
      Health Insurance Program; (2) developing pediatric-specific care coordination
      guidelines, quality metrics, and network adequacy standards to improve pediatric
      care delivery; and (3) producing cost savings by reducing fragmentation in care
      delivery, while providing a payment model that provides a significant measure of
      budget certainty for states and the federal government, either through a bundled
      payment or a shared savings payment method. We believe that this approach will
      ensure access to appropriate care without compromising the quality of care. It
      will also provide enhanced budget certainty for Medicaid and the State Child
      Health Insurance Program.

PMID- 23547059
TI  - Does well-child care have a future in pediatrics?
AB  - The most common adult chronic diseases affect 1 in 3 adults and account for more
      than three-quarters of US health care spending. The major childhood drivers of
      adult disease are distinctly nonmedical: poverty, poor educational outcomes,
      unhealthy social and physical environments, and unhealthy lifestyle choices.
      Ideally, well-child care (WCC) would address these drivers and help create
      healthier adults with more productive lives and lower health care costs. For
      children without serious acute and chronic medical problems, however, traditional
      pediatric preventive services may be largely ineffective in addressing the
      outcomes that really matter; that is, improving lifelong health and reducing the
      burden of adult chronic disease. In this article, we examine what role WCC has in
      addressing the major childhood drivers of adult disease and consider various
      models for the future of WCC within pediatrics.

PMID- 23547061
TI  - Kawasaki disease.

PMID- 23547062
TI  - Pelvic inflammatory disease.

PMID- 23547064
TI  - How to approach neutropenia in childhood.

PMID- 23547065
TI  - Obese 11-month-old female with round facies.

PMID- 23547066
TI  - Index of suspicion. Case 1: Fatigue, weakness, body aches, and metabolic
      alkalosis in a 15-year-old boy. Case 2: Refractory hypotension, tachycardia,
      hyperglycemia, and metabolic acidosis in an afebrile teen.

PMID- 23547067
TI  - Bacillus cereus.

PMID- 23547068
TI  - A 3-month-old male with wheezing.

PMID- 23547069
TI  - BRAF V600E mutation identifies a subset of low-grade diffusely infiltrating
      gliomas in adults.

PMID- 23547070
TI  - Molecular profiling for druggable genetic abnormalities in carcinoma of unknown
      primary.

PMID- 23547071
TI  - Evolving panorama of treatment for metastatic pancreas adenocarcinoma.

PMID- 23547072
TI  - Juxtaglomerular cell tumor: multicentric synchronous disease associated with
      paraneoplastic syndrome.

PMID- 23547073
TI  - Radiotherapy for hepatocellular carcinoma with tumor vascular thrombus: ready for
      prime time?

PMID- 23547074
TI  - What is the role of stem-cell transplantation for follicular non-hodgkin lymphoma
      in the rituximab era?

PMID- 23547075
TI  - Sequential phase I and II trials of stereotactic body radiotherapy for locally
      advanced hepatocellular carcinoma.
AB  - PURPOSE: To describe outcomes of prospective trials of stereotactic body
      radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Two
      trials of SBRT for patients with active HCC unsuitable for standard locoregional
      therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh
      class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was
      24 to 54 Gy in six fractions. Primary end points were toxicity and local control
      at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by
      RECIST (Response Evaluation Criteria in Solid Tumors). RESULTS: A total of 102
      patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n
      = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C
      in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent
      received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61%
      had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to
      1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic
      disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard
      ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were
      associated with LC1y on univariate analysis. Toxicity >= grade 3 was seen in 30%
      of patients. In seven patients (two with TVT PD), death was possibly related to
      treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months
      (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being
      in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis.
      CONCLUSION: These results provide strong rationale for studying SBRT for HCC in a
      randomized trial.

PMID- 23547076
TI  - Decitabine in older adults with acute myeloid leukemia: why was the dream broken?

PMID- 23547077
TI  - Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with
      pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute
      leukemia.
AB  - PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow
      failure in patients with Fanconi anemia (FA). Data on outcomes in patients with
      pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or
      acute leukemia have not been separately analyzed. PATIENTS AND METHODS: We
      analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54),
      MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for
      International Blood and Marrow Transplant Research from 1985 to 2007. RESULTS:
      Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100,
      respectively. Day 100 cumulative incidences of acute graft-versus-host disease
      grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to
      19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI,
      55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%),
      respectively. In univariate analysis, younger age was associated with superior 5
      year survival (<= v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to
      53%], respectively; P = .001). In transplantations from HLA-matched related
      donors (n = 82), younger patients (<= v > 14 years: 78% [95% CI, 64% to 90%] v
      34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic
      abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95%
      CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. CONCLUSION:
      Our analysis indicates that long-term survival for patients with FA with
      cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients
      and recipients of HLA-matched related donor transplantations who have cytogenetic
      abnormalities only have the best survival.

PMID- 23547078
TI  - Rituximab purging and/or maintenance in patients undergoing autologous
      transplantation for relapsed follicular lymphoma: a prospective randomized trial
      from the lymphoma working party of the European group for blood and marrow
      transplantation.
AB  - PURPOSE: The objective of this randomized trial was to assess the efficacy and
      safety of rituximab as in vivo purging before transplantation and as maintenance
      treatment immediately after high-dose chemotherapy and autologous stem-cell
      transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma (FL).
      PATIENTS AND METHODS: Patients with relapsed FL who achieved either complete or
      very good partial remission with salvage chemotherapy were randomly assigned
      using a factorial design to rituximab purging (P+; 375 mg/m(2) once per week for
      4 weeks) or observation (NP) before HDC-ASCT and to maintenance rituximab (M+;
      375 mg/m(2) once every 2 months for four infusions) or observation (NM). RESULTS:
      From October 1999 to April 2006, 280 patients were enrolled. The median age was
      51 years (range, 26 to 70 years), and baseline characteristics were well balanced
      between groups. On average, patients were 44 months (range, 3 to 464 months) from
      diagnosis, with 79% having received two lines and 15% three lines of prior
      therapy. Median follow-up was 8.3 years. In contrast to purging, 10-year
      progression-free survival (PFS) was 48% for P+ and 42% for NP groups (hazard
      ratio [HR], 0.80; 95% CI, 0.58 to 1.11; P = .18); maintenance had a significant
      effect on PFS (10-year PFS, 54% for M+ and 37% for NM; HR, 0.66; 95% CI, 0.47 to
      0.91; P = .012). Overall survival (OS) was not improved by either rituximab
      purging or maintenance. CONCLUSION: Rituximab maintenance after HDC-ASCT is safe
      and significantly prolongs PFS but not OS in patients undergoing transplantation
      for relapsed FL. Pretransplantation rituximab in vivo purging, even in rituximab
      naive patients, failed to improve PFS or OS.

PMID- 23547079
TI  - 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage
      follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3
      years from the International, Randomized, Phase III First-LineIndolent trial.
AB  - PURPOSE: Updated results are presented after a median follow-up of 7.3 years from
      the phase III First-Line Indolent Trial of yttrium-90 ((90)Y) -ibritumomab
      tiuxetan in advanced-stage follicular lymphoma (FL) in first remission. PATIENTS
      AND METHODS: Patients with CD20(+) stage III or IV FL with complete response
      (CR), unconfirmed CR (CRu), or partial response (PR) after first-line induction
      treatment were randomly assigned to (90)Y-ibritumomab consolidation therapy
      (rituximab 250 mg/m(2) days -7 and 0, then (90)Y-ibritumomab 14.8 MBq/kg day 0;
      maximum 1,184 MBq) or no further treatment (control). Primary end point was
      progression-free survival (PFS) from date of random assignment. RESULTS: For 409
      patients available for analysis ((90)Y-ibritumomab, n = 207; control, n = 202),
      estimated 8-year overall PFS was 41% with (90)Y-ibritumomab versus 22% for
      control (hazard ratio [HR], 0.47; P < .001). For patients in CR/CRu after
      induction, 8-year PFS with (90)Y-ibritumomab was 48% versus 32% for control (HR,
      0.61; P = .008), and for PR patients, it was 33% versus 10% (HR, 0.38; P < .001).
      For (90)Y-ibritumomab consolidation, median PFS was 4.1 years (v 1.1 years for
      control; P < .001). Median time to next treatment (TTNT) was 8.1 years for (90)Y
      ibritumomab versus 3.0 years for control (P < .001) with approximately 80%
      response rates to second-line therapy in either arm, including autologous stem
      cell transplantation. No unexpected toxicities emerged during long-term follow
      up. Estimated between-group 8-year overall survival rates were similar.
      Annualized incidence rate of myelodysplastic syndrome/acute myeloblastic leukemia
      was 0.50% versus 0.07% in (90)Y-ibritumomab and control groups, respectively (P =
      .042). CONCLUSION: (90)Y-ibritumomab consolidation after achieving PR or CR/CRu
      to induction confers 3-year benefit in median PFS with durable 19% PFS advantage
      at 8 years and improves TTNT by 5.1 years for patients with advanced FL.

PMID- 23547080
TI  - But some neoadjuvant schedules are more equal than others.

PMID- 23547083
TI  - Short-course preoperative radiotherapy for low rectal cancer.

PMID- 23547082
TI  - Ring-enhancing lesion associated with radiation-induced liver disease.

PMID- 23547081
TI  - Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine
      alone in patients with locally advanced and metastatic pancreatic cancer in Japan
      and Taiwan: GEST study.
AB  - PURPOSE: The present phase III study was designed to investigate the
      noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with
      gemcitabine alone with respect to overall survival. PATIENTS AND METHODS: The
      participants were chemotherapy-naive patients with locally advanced or metastatic
      pancreatic cancer. Patients were randomly assigned to receive only gemcitabine
      (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120
      mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or
      gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80,
      or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day
      cycle). RESULTS: In the total of 834 enrolled patients, median overall survival
      was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1
      months in the gemcitabine plus S-1 group. The noninferiority of S-1 to
      gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P <
      .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not
      (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were
      generally well tolerated, although hematologic and GI toxicities were more severe
      in the gemcitabine plus S-1 group than in the gemcitabine group. CONCLUSION:
      Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall
      survival with good tolerability and presents a convenient oral alternative for
      locally advanced and metastatic pancreatic cancer.

PMID- 23547085
TI  - Cadherin adhesome at a glance.

PMID- 23547084
TI  - Associations between cigarette smoking status and colon cancer prognosis among
      participants in North Central Cancer Treatment Group Phase III Trial N0147.
AB  - PURPOSE: By using data from North Central Cancer Treatment Group Phase III Trial
      N0147, a randomized adjuvant trial of patients with stage III colon cancer, we
      assessed the relationship between smoking and cancer outcomes, disease-free
      survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by
      patient and tumor characteristics. PATIENTS AND METHODS Before random assignment
      to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus
      cetuximab, 1,968 participants completed a questionnaire on smoking history and
      other risk factors. Cox models assessed the association between smoking history
      and the primary trial outcome of DFS (ie, time to recurrence or death), as well
      as TTR, adjusting for other clinical and patient factors. The median follow-up
      was 3.5 years among patients who did not experience events. RESULTS: Compared
      with never-smokers, ever smokers experienced significantly shorter DFS (3-year
      DFS proportion: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This
      association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to
      1.49). There was significant interaction in this association by BRAF mutation
      status (P = .03): smoking was associated with shorter DFS in patients with BRAF
      wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95%
      CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer
      DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95%
      CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by
      KRAS mutation status was not statistically significant (P = .07). Associations
      were comparable in analyses of TTR. CONCLUSION: Overall, smoking was
      significantly associated with shorter DFS and TTR in patients with colon cancer.
      These adverse relationships were most evident in patients with BRAF wild-type or
      KRAS mutated colon cancer.

PMID- 23547086
TI  - Cycling around cell-cell adhesion with Rho GTPase regulators.
AB  - The formation and stability of epithelial adhesive systems, such as adherens
      junctions, desmosomes and tight junctions, rely on a number of cellular processes
      that ensure a dynamic interaction with the cortical cytoskeleton, and appropriate
      delivery and turnover of receptors at the surface. Unique signalling pathways
      must be coordinated to allow the coexistence of distinct adhesive systems at
      discrete sub-domains along junctions and the specific properties they confer to
      epithelial cells. Rho, Rac and Cdc42 are members of the Rho small GTPase family,
      and are well-known regulators of cell-cell adhesion. The spatio-temporal control
      of small GTPase activation drives specific intracellular processes to enable the
      hierarchical assembly, morphology and maturation of cell-cell contacts. Here, we
      discuss the small GTPase regulators that control the precise amplitude and
      duration of the levels of active Rho at cell-cell contacts, and the mechanisms
      that tailor the output of Rho signalling to a particular cellular event.
      Interestingly, the functional interaction is reciprocal; Rho regulators drive the
      maturation of cell-cell contacts, whereas junctions can also modulate the
      localisation and activity of Rho regulators to operate in diverse processes in
      the epithelial differentiation programme.

PMID- 23547087
TI  - Resistance of man and bug.

PMID- 23547088
TI  - Short QT syndrome (JANUARY 2013).

PMID- 23547089
TI  - Author's reply: To PMID 23288944.

PMID- 23547090
TI  - Implications of a prominent R wave in V1.

PMID- 23547091
TI  - Detecting and controlling diabetic nephropathy: what do we know?
AB  - Diabetic nephropathy is becoming increasingly common with the aging of our
      population and the obesity epidemic. The major ways to prevent or slow its
      progression are by reducing blood pressure, controlling blood sugar, and
      inhibiting the renin-angiotensin-aldosterone axis. New therapeutic agents are
      also being tried.

PMID- 23547092
TI  - A rapidly growing crusted nodule on the lip.

PMID- 23547093
TI  - Carbapenem-resistant Enterobacteriaceae: a menace to our most vulnerable
      patients.
AB  - The emergence of carbapenem-resistant Enterobacteriaceae (CRE) highlights the
      importance of effective antibiotics to maintain the safety of our health care
      system. Clinicians will encounter CRE as a cause of difficult-to-treat and often
      fatal infections in hospitalized patients. We review the mechanisms of carbapenem
      resistance, the dissemination and clinical impact of these resistant organisms,
      and challenges to their detection, treatment, and control.

PMID- 23547094
TI  - Bone mineral density testing: is a T score enough to determine the screening
      interval?
AB  - To find the rational intervals for bone mineral density screening, Gourlay et al
      (N Engl J Med 2012; 366:225-233) used T scores to calculate the time required for
      women age 67 and older with normal bone mineral density or osteopenia to progress
      to osteoporosis. They estimated that the screening interval for women with normal
      bone mineral density or mild osteopenia (T score -1.49 or higher) could be as
      long as 15 years. However, the investigators focused mainly on T scores and when
      these scores reached -2.5. In our opinion, the testing interval should be guided
      by an assessment of clinical risk factors and not just baseline T scores.

PMID- 23547095
TI  - What should be the interval between bone density screenings?

PMID- 23547096
TI  - Options for managing severe aortic stenosis: a case-based review.
AB  - The treatment of calcific aortic stenosis is well established and includes
      careful monitoring of patients who have no symptoms and surgical aortic valve
      replacement in the patients who do have symptoms. Patients who cannot undergo
      open heart surgery can now undergo valve replacement via a minimally invasive
      transcatheter approach. In this article, we use clinical vignettes to illustrate
      the management of patients with severe aortic stenosis.

PMID- 23547097
TI  - Aortic valve replacement: options, improvements, and costs.

PMID- 23547098
TI  - Systemic 4-1BB activation induces a novel T cell phenotype driven by high
      expression of Eomesodermin.
AB  - 4-1BB agonist antibody treatment induces a population of KLRG1(+) T cells that
      infiltrate melanoma tumors. We investigated the origin and function of these
      cells, as well as their place within established T cell paradigms. We find that
      these T cells, particularly the CD4 lineage, represent a novel phenotype
      characterized by enhanced, multipotent cytotoxicity. Distinct from described
      polarities, this T cell phenotype is driven by the T-box transcription factor
      Eomesodermin. Formation of this phenotype requires 4-1BB signaling on both T and
      antigen-presenting cells and the resulting production of the cytokines IL-27, IL
      15, and IL-10. Furthermore, we find CD4(+) T cells bearing the signature features
      of this phenotype in the livers of mice infected with both bacterial and viral
      intracellular pathogens, suggesting a role for these cells in infectious
      immunity. These T cells constitute a novel phenotype that resolves multiple
      questions associated with 4-1BB activation, including how 4-1BB enhances tumor
      specific cytotoxicity and how 4-1BB can promote tumor immunity while repressing
      autoimmunity.

PMID- 23547099
TI  - Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+
      regulatory T cell development via the CD27-CD70 pathway.
AB  - CD4(+)Foxp3(+) regulatory T cells (Treg cells) are largely autoreactive yet
      escape clonal deletion in the thymus. We demonstrate here that CD27-CD70 co
      stimulation in the thymus rescues developing Treg cells from apoptosis and
      thereby promotes Treg cell generation. Genetic ablation of CD27 or its ligand
      CD70 reduced Treg cell numbers in the thymus and peripheral lymphoid organs,
      whereas it did not alter conventional CD4(+)Foxp3(-) T cell numbers. The CD27
      CD70 pathway was not required for pre-Treg cell generation, Foxp3 induction, or
      mature Treg cell function. Rather, CD27 signaling enhanced positive selection of
      Treg cells within the thymus in a cell-intrinsic manner. CD27 signals promoted
      the survival of thymic Treg cells by inhibiting the mitochondrial apoptosis
      pathway. CD70 was expressed on Aire(-) and Aire(+) medullary thymic epithelial
      cells (mTECs) and on dendritic cells (DCs) in the thymic medulla. CD70 on both
      mTECs and DCs contributed to Treg cell development as shown in BM chimera
      experiments with CD70-deficient mice. In vitro experiments indicated that CD70 on
      the CD8alpha(+) subset of thymic DCs promoted Treg cell development. Our data
      suggest that mTECs and DCs form dedicated niches in the thymic medulla, in which
      CD27-CD70 co-stimulation rescues developing Treg cells from apoptosis, subsequent
      to Foxp3 induction by TCR and CD28 signals.

PMID- 23547100
TI  - Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth
      disease type 1B mice.
AB  - P0 glycoprotein is an abundant product of terminal differentiation in myelinating
      Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in
      humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del
      is retained in the endoplasmic reticulum of Schwann cells, where it promotes
      unfolded protein stress and elicits an unfolded protein response (UPR) associated
      with translational attenuation. Ablation of Chop, a UPR mediator, from S63del
      mice completely rescues their motor deficit and reduces active demyelination by
      half. Here, we show that Gadd34 is a detrimental effector of CHOP that
      reactivates translation too aggressively in myelinating Schwann cells. Genetic or
      pharmacological limitation of Gadd34 function moderates translational
      reactivation, improves myelination in S63del nerves, and reduces accumulation of
      P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic
      strategy in tissues impaired by misfolded proteins that are synthesized during
      terminal differentiation.

PMID- 23547101
TI  - Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote
      airway tolerance.
AB  - Airway tolerance is the usual outcome of inhalation of harmless antigens.
      Although T cell deletion and anergy are likely components of tolerogenic
      mechanisms in the lung, increasing evidence indicates that antigen-specific
      regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are
      also critical. Several lung antigen-presenting cells have been suggested to
      contribute to tolerance, including alveolar macrophages (MOs), classical
      dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the
      attributes required to directly promote the development of Foxp3(+) iTreg cells
      is unclear. Here, we show that lung-resident tissue MOs coexpress TGF-beta and
      retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and
      that their sampling of harmless airborne antigen and presentation to antigen
      specific CD4 T cells resulted in the generation of Foxp3(+) Treg cells. Treg cell
      induction in this model depended on both TGF-beta and retinoic acid. Transfer of
      the antigen-pulsed tissue MOs into the airways correspondingly prevented the
      development of asthmatic lung inflammation upon subsequent challenge with
      antigen. Moreover, exposure of lung tissue MOs to allergens suppressed their
      ability to generate iTreg cells coincident with blocking airway tolerance.
      Suppression of Treg cell generation required proteases and TLR-mediated signals.
      Therefore, lung-resident tissue MOs have regulatory functions, and strategies to
      target these cells might hold promise for prevention or treatment of allergic
      asthma.

PMID- 23547102
TI  - Veratrole biosynthesis in white campion.
AB  - White campion (Silene latifolia) is a dioecious plant that emits 1,2
      dimethoxybenzene (veratrole), a potent pollinator attractant to the nocturnal
      moth Hadena bicruris. Little is known about veratrole biosynthesis, although
      methylation of 2-methoxyphenol (guaiacol), another volatile emitted from white
      campion flowers, has been proposed. Here, we explore the biosynthetic route to
      veratrole. Feeding white campion flowers with [(13)C9]l-phenylalanine increased
      guaiacol and veratrole emission, and a significant portion of these volatile
      molecules contained the stable isotope. When white campion flowers were treated
      with the phenylalanine ammonia lyase inhibitor 2-aminoindan-2-phosphonic acid,
      guaiacol and veratrole levels were reduced by 50% and 63%, respectively. Feeding
      with benzoic acid (BA) or salicylic acid (SA) increased veratrole emission 2
      fold, while [(2)H5]BA and [(2)H6]SA feeding indicated that the benzene ring of
      both guaiacol and veratrole is derived from BA via SA. We further report guaiacol
      O-methyltransferase (GOMT) activity in the flowers of white campion. The enzyme
      was purified to apparent homogeneity, and the peptide sequence matched that
      encoded by a recently identified complementary DNA (SlGOMT1) from a white campion
      flower expressed sequence tag database. Screening of a small population of North
      American white campion plants for floral volatile emission revealed that not all
      plants emitted veratrole or possessed GOMT activity, and SlGOMT1 expression was
      only observed in veratrole emitters. Collectively these data suggest that
      veratrole is derived by the methylation of guaiacol, which itself originates from
      phenylalanine via BA and SA, and therefore implies a novel branch point of the
      general phenylpropanoid pathway.

PMID- 23547103
TI  - Visual consciousness and intertrial feature priming.
AB  - Intertrial repetition priming plays a striking role in visual search. For
      instance, when searching for a target with a unique color, performance is
      substantially better when the specific color of the target repeats on successive
      trials (Maljkovic & Nakayama, 1994). Recent research has relied on objective
      measures of performance to show that priming improves the perceptual quality of
      the repeated target. Here, we examined the relation between priming and conscious
      perception of the target by adding a subjective measure of perception. We used
      backward masking to create liminal perception, that is, different levels of
      subjectively conscious perception of the target using exactly the same stimulus
      conditions. The displays in either probe trials (in which priming benefits are
      measured, experiment 1) or in prime trials (in which memory traces are laid down,
      experiment 2) were masked. The results showed that intertrial priming improves
      full access to awareness of the repeated target but only for targets that already
      achieved partial access to awareness. In addition, they show that full awareness
      of the target is necessary in both the prime and probe trials for intertrial
      priming effects to emerge. Implications for the role of implicit short-term
      memory in visual search are discussed.

PMID- 23547104
TI  - Object-based saccadic selection during scene perception: evidence from viewing
      position effects.
AB  - The goal of the present study was to further test the hypothesis that objects are
      important units of saccade targeting and, by inference, attentional selection in
      real-world scene perception. To this end, we investigated where people fixate
      within objects embedded in natural scenes. Previously, we reported a preferred
      viewing location (PVL) close to the center of objects (Nuthmann & Henderson,
      2010). Here, we qualify this basic finding by showing that the PVL is affected by
      object size and the distance between the object and the previous fixation (i.e.,
      launch site distance). Moreover, we examined how within-object fixation position
      affected subsequent eye-movement behavior on the object. Unexpectedly, there was
      no refixation optimal viewing position (OVP) effect for objects in scenes. Where
      viewers initially placed their eyes on an object did not affect the likelihood of
      refixating that object, suggesting that some refixations on objects in scenes are
      made for reasons other than insufficient visual information. A fixation-duration
      inverted-optimal viewing (IOVP) effect was found for large objects: Fixations
      located at object center were longer than those falling near the edges of an
      object. Collectively, these findings lend further support to the notion of object
      based saccade targeting in scenes.

PMID- 23547105
TI  - Flash illusions induced by visual, auditory, and audiovisual stimuli.
AB  - When two objects are flashed at one location in close temporal proximity in the
      visual periphery, an intriguing illusion occurs whereby a single flash presented
      concurrently at another location appears to flash twice (the visual double-flash
      illusion: Chatterjee et al., 2011, Wilson & Singer, 1981). Here, for the first
      time, we investigate the time course of the effect, and directly compare it to
      the time course of the auditory (sound-induced flash illusion) effect, for both
      fission (single test flash, double inducer) and fusion (double test flash, single
      inducer) conditions, across stimulus onset asynchronies (SOAs) of 30 to 250 ms.
      In addition, using a novel audiovisual stimulus, we directly compare the cue
      strength of the two modalities, and whether they are additive in effect. The
      results show that the time course of fission and fusion is different for visual
      inducers, but not for auditory inducers. In audiovisual conditions, in situations
      of uncertainty, observers tended to follow the more reliable (auditory) cue.
      There was little evidence for a superadditive effect of auditory and visual cues;
      rather, observers tended to follow one or the other modality. The results suggest
      that the visually induced flash illusion and the auditory-induced effect may both
      stem from perceptual uncertainty, with the difference in time courses
      attributable to the lower temporal resolution of vision compared to audition.

PMID- 23547106
TI  - Life, redrawn: a memoir of Carl R. Woese (1928-2012).

PMID- 23547107
TI  - The Arabidopsis general transcription factor TFIIB1 (AtTFIIB1) is required for
      pollen tube growth and endosperm development.
AB  - Pollen tube growth and endosperm development are important for fertilization and
      seed formation. The genetic mechanism of the processes remains poorly understood.
      This study reports the functional characterization of AtTFIIB1 in pollen tube
      growth and endosperm development. AtTFIIB1 shares 86% and 44% similarity with
      AtTFIIB2 and AtTFIIB3/AtpBRP2, respectively. It is expressed in many tissues
      including vegetative nuclei and generative cells of pollen grains and pollen
      tubes, endosperm, and embryos. It is thus different from AtTFIIB2, whose
      expression is not found in the endosperm and vegetative nucleus of mature pollen,
      and AtTFIIB3/AtpBRP2, which is expressed mostly in male gametophytes and weakly
      in seeds. Mutations in AtTFIIB1 caused a drastic retardation of pollen tube
      growth and endosperm development, as well as impaired pollen tube guidance and
      reception, leading to disruption of fertilization and seed development.
      Expression of AtTFIIB2 driven by the AtTFIIB1 promoter could restore the
      defective pollen tube growth, guidance, and reception completely, but only
      partially recovered the seed development in attfiib1, whilst expression of
      AtTFIIB3/AtpBRP2 driven by the AtTFIIB1 promoter could rescue only the defective
      attfiib1 seeds. All these results suggest that AtTFIIB1 plays important roles in
      pollen tube growth, guidance, and reception as well as endosperm development and
      is partially functionally different from AtTFIIB2 and AtTFIIB3/AtpBRP2.

PMID- 23547108
TI  - Transgenic wheat expressing Thinopyrum intermedium MYB transcription factor
      TiMYB2R-1 shows enhanced resistance to the take-all disease.
AB  - The disease take-all, caused by the fungus Gaeumannomyces graminis, is one of the
      most destructive root diseases of wheat worldwide. Breeding resistant cultivars
      is an effective way to protect wheat from take-all. However, little progress has
      been made in improving the disease resistance level in commercial wheat
      cultivars. MYB transcription factors play important roles in plant responses to
      environmental stresses. In this study, an R2R3-MYB gene in Thinopyrum
      intermedium, TiMYB2R-1, was cloned and characterized. The gene sequence includes
      two exons and an intron. The expression of TiMYB2R-1 was significantly induced
      following G. graminis infection. An in vitro DNA binding assay proved that
      TiMYB2R-1 protein could bind to the MYB-binding site cis-element ACI. Subcellular
      localization assays revealed that TiMYB2R-1 was localized in the nucleus. TiMYB2R
      1 transgenic wheat plants were generated, characterized molecularly, and
      evaluated for take-all resistance. PCR and Southern blot analyses confirmed that
      TiMYB2R-1 was integrated into the genomes of three independent transgenic wheat
      lines by distinct patterns and the transgene was heritable. Reverse transcription
      PCR and western blot analyses revealed that TiMYB2R-1 was highly expressed in the
      transgenic wheat lines. Based on disease response assessments for three
      successive generations, the significantly enhanced resistance to take-all was
      observed in the three TiMYB2R-1-overexpressing transgenic wheat lines.
      Furthermore, the transcript levels of at least six wheat defence-related genes
      were significantly elevated in the TiMYB2R-1 transgenic wheat lines. These
      results suggest that engineering and overexpression of TiMYB2R-1 may be used for
      improving take-all resistance of wheat and other cereal crops.

PMID- 23547109
TI  - Arabidopsis thaliana as a model species for xylem hydraulics: does size matter?
AB  - While Arabidopsis thaliana has been proposed as a model species for wood
      development, the potential of this tiny herb for studying xylem hydraulics
      remains unexplored and anticipated by scepticism. Inflorescence stems of A.
      thaliana were used to measure hydraulic conductivity and cavitation resistance,
      whereas light and electron microscopy allowed observations of vessels. In wild
      type plants, measured and theoretical conductivity showed a significant
      correlation (R (2) = 0.80, P < 0.01). Moreover, scaling of vessel dimensions and
      intervessel pit structure of A. thaliana were consistent with structure-function
      relationships of woody plants. The reliability and resolution of the hydraulic
      methods applied to measure vulnerability to cavitation were addressed by
      comparing plants grown under different photoperiods or different mutant lines.
      Sigmoid vulnerability curves of A. thaliana indicated a pressure corresponding to
      50% loss of hydraulic conductance (P 50) between -3 and -2.5MPa for short-day and
      long-day plants, respectively. Polygalacturonase mutants showed a higher P 50
      value (-2.25MPa), suggesting a role for pectins in vulnerability to cavitation.
      The application of A. thaliana as a model species for xylem hydraulics provides
      exciting possibilities for (1) exploring the molecular basis of xylem anatomical
      features and (2) understanding genetic mechanisms behind xylem functional traits
      such as cavitation resistance. Compared to perennial woody species, however, the
      lesser amount of xylem in A. thaliana has its limitations.

PMID- 23547110
TI  - Pathway-based personalized analysis of cancer.
AB  - We introduce Pathifier, an algorithm that infers pathway deregulation scores for
      each tumor sample on the basis of expression data. This score is determined, in a
      context-specific manner, for every particular dataset and type of cancer that is
      being investigated. The algorithm transforms gene-level information into pathway
      level information, generating a compact and biologically relevant representation
      of each sample. We demonstrate the algorithm's performance on three colorectal
      cancer datasets and two glioblastoma multiforme datasets and show that our
      multipathway-based representation is reproducible, preserves much of the original
      information, and allows inference of complex biologically significant
      information. We discovered several pathways that were significantly associated
      with survival of glioblastoma patients and two whose scores are predictive of
      survival in colorectal cancer: CXCR3-mediated signaling and oxidative
      phosphorylation. We also identified a subclass of proneural and neural
      glioblastoma with significantly better survival, and an EGF receptor-deregulated
      subclass of colon cancers.

PMID- 23547111
TI  - Sex-biased gene expression at homomorphic sex chromosomes in emus and its
      implication for sex chromosome evolution.
AB  - Sex chromosomes originate from autosomes. The accumulation of sexually
      antagonistic mutations on protosex chromosomes selects for a loss of
      recombination and sets in motion the evolutionary processes generating
      heteromorphic sex chromosomes. Recombination suppression and differentiation are
      generally viewed as the default path of sex chromosome evolution, and the
      occurrence of old, homomorphic sex chromosomes, such as those of ratite birds,
      has remained a mystery. Here, we analyze the genome and transcriptome of emu
      (Dromaius novaehollandiae) and confirm that most genes on the sex chromosome are
      shared between the Z and W. Surprisingly, however, levels of gene expression are
      generally sex-biased for all sex-linked genes relative to autosomes, including
      those in the pseudoautosomal region, and the male-bias increases after gonad
      formation. This expression bias suggests that the emu sex chromosomes have become
      masculinized, even in the absence of ZW differentiation. Thus, birds may have
      taken different evolutionary solutions to minimize the deleterious effects
      imposed by sexually antagonistic mutations: some lineages eliminate recombination
      along the protosex chromosomes to physically restrict sexually antagonistic
      alleles to one sex, whereas ratites evolved sex-biased expression to confine the
      product of a sexually antagonistic allele to the sex it benefits. This difference
      in conflict resolution may explain the preservation of recombining, homomorphic
      sex chromosomes in other lineages and illustrates the importance of sexually
      antagonistic mutations driving the evolution of sex chromosomes.

PMID- 23547112
TI  - TAK1-JNK axis mediates survival signal through Mcl1 stabilization in activated T
      cells.
AB  - TAK1, a member of MAPK kinase kinase (MAPKK-K) family, can activate JNK, p38
      MAPK, and NF-kappaB signaling pathways. Although targeted gene disruption studies
      have demonstrated that TAK1 plays a critical role in T cell functions, precise
      functions of downstream mediators remain elusive. We used the chemical compound
      LL-Z1640-2, which preferentially suppressed MAPK activation but not NF-kappaB
      signal downstream of TAK1. LL-Z1640-2 blocked TCR-induced T cell proliferation
      and activation, confirming that a TAK1-mediated MAPK signal is essential for T
      cell activation. LL-Z1640-2 induced apoptosis of activated mouse splenic T cells
      in a caspase- and caspase-activated DNase-dependent manner. TAK1-JNK pathway,
      which is activated downstream of IL-2R, induced the phosphorylation of
      antiapoptotic protein Mcl1 in activated T cells, resulting in the stabilization
      of Mcl1 protein. Our data uncover that among signal transduction pathways
      downstream of TAK1, JNK mediates a survival program through Mcl1 stabilization
      downstream of IL-2R in activated T cells and that blockade of TAK1-JNK pathway
      can eliminate activated T cells by apoptosis.

PMID- 23547113
TI  - A stimulation-dependent alternate core promoter links lymphotoxin alpha
      expression with TGF-beta1 and fibroblast growth factor-7 signaling in primary
      human T cells.
AB  - Lymphotoxin (LT)-alpha regulates many biologic activities, yet little is known of
      the regulation of its gene. In this study, the contribution to LTA
      transcriptional regulation of the region between the transcription and
      translation start sites (downstream segment) was investigated. The LTA downstream
      segment was found to be required for, and alone to be sufficient for, maximal
      transcriptional activity in both T and B lymphocytes. The latter observation
      suggested that an alternate core promoter might be present in the downstream
      segment. Characterization of LTA mRNAs isolated from primary and from transformed
      human T cells under different stimulation conditions identified eight unique
      transcript variants (TVs), including one (LTA TV8) that initiated within a
      polypyrimidine tract near the 3' end of the downstream segment. Further
      investigation determined that the LTA downstream segment alternate core promoter
      that produces the LTA TV8 transcript most likely consists of a stimulating
      protein 1 binding site and an initiator element and that factors involved in
      transcription initiation (stimulating protein 1, TFII-I, and RNA polymerase II)
      bind to this LTA region in vivo. Interestingly, the LTA downstream segment
      alternate core promoter was active only after specific cellular stimulation and
      was the major promoter used when human T cells were stimulated with TGF-beta1 and
      fibroblast growth factor-7. Most importantly, this study provides evidence of a
      direct link for crosstalk between T cells and epithelial/stromal cells that has
      implications for LT signaling by T cells in the cooperative regulation of various
      processes typically associated with TGF-betaR and fibroblast growth factor-R2
      signaling.

PMID- 23547114
TI  - IkappaBzeta is a transcriptional key regulator of CCL2/MCP-1.
AB  - CCL2, also referred to as MCP-1, is critically involved in directing the
      migration of blood monocytes to sites of inflammation. Consequently, excessive
      CCL2 secretion has been linked to many inflammatory diseases, whereas a lack of
      expression severely impairs immune responsiveness. We demonstrate that
      IkappaBzeta, an atypical IkappaB family member and transcriptional coactivator
      required for the selective expression of a subset of NF-kappaB target genes, is a
      key activator of the Ccl2 gene. IkappaBzeta-deficient macrophages exhibited
      impaired secretion of CCL2 when challenged with diverse inflammatory stimuli,
      such as LPS or peptidoglycan. These findings were reflected at the level of Ccl2
      gene expression, which was tightly coupled to the presence of IkappaBzeta.
      Moreover, mechanistic insights acquired by chromatin immunoprecipitation
      demonstrate that IkappaBzeta is directly recruited to the proximal promoter
      region of the Ccl2 gene and is required for transcription-enhancing histone H3 at
      lysine-4 trimethylation. Finally, IkappaBzeta-deficient mice showed significantly
      impaired CCL2 secretion and monocyte infiltration in an experimental model of
      peritonitis. Together, these findings suggest a distinguished role of IkappaBzeta
      in mediating the targeted recruitment of monocytes in response to local
      inflammatory events.

PMID- 23547116
TI  - Clinical-grade multipotent adult progenitor cells durably control pathogenic T
      cell responses in human models of transplantation and autoimmunity.
AB  - A major goal of immunotherapy remains the control of pathogenic T cell responses
      that drive autoimmunity and allograft rejection. Adherent progenitor cells,
      including mesenchymal stromal cells (MSCs) and multipotent adult progenitor cells
      (MAPCs), represent attractive immunomodulatory cell therapy candidates currently
      active in clinical trials. MAPCs can be distinguished from MSCs on the basis of
      cellular phenotype, size, transcriptional profile, and expansion capacity.
      However, despite their ongoing evaluation in autoimmune and allogeneic solid
      organ transplantation settings, data supporting the immune regulatory potential
      of clinical-grade MAPCs are limited. In this study, we used allogeneic islet
      transplantation as a model indication to assess the ability of clinical-grade
      MAPCs to control T cell responses that drive immunopathology in human autoimmune
      disease and allograft rejection. MAPCs suppressed T cell proliferation and Th1
      and Th17 cytokine production while increasing secretion of IL-10 and were able to
      suppress effector functions of bona fide autoreactive T cells from individuals
      with type 1 diabetes mellitus, including killing of human islets. Furthermore,
      MAPCs favored the proliferation of regulatory T cells during homeostatic
      expansion driven by gamma-chain cytokines and exerted a durable, yet reversible,
      control of T cell function. MAPC suppression required licensing and proceeded via
      IDO-mediated tryptophan catabolism. Therefore, the common immune modulatory
      characteristics of clinical-grade MAPCs shown in this study suggest that they can
      be regarded as an alternative source of adult progenitor cells with similar
      clinical usefulness to MSCs. Taken collectively, these findings may guide the
      successful deployment of both MSCs and MAPCs for the amelioration of human
      autoimmunity and allograft rejection.

PMID- 23547117
TI  - IL-33-mediated innate response and adaptive immune cells contribute to maximum
      responses of protease allergen-induced allergic airway inflammation.
AB  - How the innate and adaptive immune systems cooperate in the natural history of
      allergic diseases has been largely unknown. Plant-derived allergen, papain, and
      mite allergens, Der f 1 and Der p 1, belong to the same family of cysteine
      proteases. We examined the role of protease allergens in the induction of Ab
      production and airway inflammation after repeated intranasal administration
      without adjuvants and that in basophil/mast cell stimulation in vitro. Papain
      induced papain-specific IgE/IgG1 and lung eosinophilia. Der f 1 induced Der f 1
      specific IgG1 and eosinophilia. Although papain-, Der f 1-, and Der p 1
      stimulated basophils expressed allergy-inducing cytokines, including IL-4 in
      vitro, basophil-depleting Ab and mast cell deficiency did not suppress the papain
      induced in vivo responses. Protease inhibitor-treated allergens and a catalytic
      site mutant did not induce the responses. These results indicate that protease
      activity is essential to Ab production and eosinophilia in vivo and basophil
      activation in vitro. IL-33-deficient mice lacked eosinophilia and had reduced
      papain-specific IgE/IgG1. Coadministration of OVA with papain induced OVA
      specific IgE/IgG1, which was reduced in IL-33-deficient mice. We demonstrated IL
      33 release, subsequent IL-33-dependent IL-5/IL-13 release, and activation of
      T1/ST2-expressing lineage(-)CD25(+)CD44(+) innate lymphoid cells in the lung
      after papain inhalation, suggesting the contribution of the IL-33-type 2 innate
      lymphoid cell-IL-5/IL-13 axis to the papain-induced airway eosinophilia. Rag2
      deficient mice, which lack adaptive immune cells, showed significant, but less
      severe, eosinophilia. Collectively, these results suggest cooperation of adaptive
      immune cells and IL-33-responsive innate cells in protease-dependent allergic
      airway inflammation.

PMID- 23547118
TI  - Intrarectal immunization and IgA antibody-secreting cell homing to the small
      intestine.
AB  - According to the current paradigm, lymphocyte homing to the small intestine
      requires the expression of two tissue-specific homing receptors, the integrin
      alpha4beta7 and the CCL25 receptor CCR9. In this study, we investigated the organ
      distribution and the homing molecule expression of IgA Ab-secreting cells (ASCs)
      induced by intrarectal immunization with a particulate Ag, in comparison with
      other mucosal immunization routes. Intrarectal immunization induces gut-homing
      IgA ASCs that localize not only in the colon but also in the small intestine,
      although they are not responsive to CCL25, unlike IgA ASCs induced by oral
      immunization. The mucosal epithelial chemokine CCL28, known to attract all IgA
      ASCs, does not compensate for the lack of CCL25 responsiveness, because the
      number of Ag-specific cells is not decreased in the gut of CCR10-deficient mice
      immunized by the intrarectal route. However, Ag-specific IgA ASCs induced by
      intrarectal immunization express the integrin alpha4beta7, and their number is
      considerably decreased in the gut of beta7-deficient mice immunized by the
      intrarectal route, indicating that alpha4beta7 enables these cells to migrate
      into the small intestine, even without CCL25 responsiveness. In contrast, IgA
      ASCs induced by intranasal immunization express low alpha4beta7 levels and are
      usually excluded from the gut. Paradoxically, after intranasal immunization, Ag
      specific IgA ASCs are significantly increased in the small intestine of beta7
      deficient mice, demonstrating that lymphocyte homing is a competitive process and
      that integrin alpha4beta7 determines not only the intestinal tropism of IgA ASCs
      elicited in GALTs but also the intestinal exclusion of lymphocytes primed in
      other inductive sites.

PMID- 23547115
TI  - Overexpression of SIRT1 protein in neurons protects against experimental
      autoimmune encephalomyelitis through activation of multiple SIRT1 targets.
AB  - Treatment of experimental autoimmune encephalomyelitis (EAE) with resveratrol, an
      activator of sirtuin 1 (SIRT1), reduces disease severity. This suggested that
      activators of SIRT1, a highly conserved NAD-dependent protein deacetylase, might
      have immune-modulating or neuroprotective therapeutic effects in EAE. Previously,
      we showed that SIRT1 expression increases in EAE, suggesting that it is an
      adaptive response. In this study, we investigated the potential function of SIRT1
      in regulating EAE using SIRT1-overexpressing mice. The current studies examine
      potential neuroprotective and immunomodulatory effects of SIRT1 overexpression in
      chronic EAE induced by immunization of C57BL/6 mice with myelin oligodendrocyte
      glycoprotein peptide 35-55. SIRT1 suppressed EAE clinical symptoms compared with
      wild-type EAE mice and prevented or altered the phenotype of inflammation in
      spinal cords; as a result, demyelination and axonal injury were reduced.
      Significant neuroprotective effects were observed, with fewer apoptotic cells
      found in the spinal cords of SIRT1-overexpressing EAE mice associated with
      increased brain-derived neurotrophic factor and NAD levels. Earlier, we showed
      that brain-derived neurotrophic factor and NAD play crucial neuroprotective roles
      in EAE. These results suggest that SIRT1 reduces neuronal loss in this chronic
      demyelinating disease model and that this is associated with a reduction in
      inflammation.

PMID- 23547119
TI  - Inoculation dose of Mycobacterium tuberculosis does not influence priming of T
      cell responses in lymph nodes.
AB  - The effect of Mycobacterium tuberculosis inocula size on T cell priming in the
      lymph node and effector T cells in the lung remains controversial. In this study,
      we used a naive mouse model, without the transfer of transgenic T cells, in
      conjunction with mathematical model to test whether infection with higher
      aerosolized inocula would lead to increased priming of M. tuberculosis-specific T
      cells in the lung-draining lymph node. Our data do not support that inoculum size
      has a measurable influence on T cell priming in the lymph nodes but is associated
      with more cells overall in the lung, including T cells. To account for increased
      T cells in the lungs, we tested several possible mechanisms, and recruitment of T
      cells to the lungs was most influenced by inoculum dose. We also identified IL-10
      as a possible mechanism to explain the lack of influence of inoculum dose on
      priming of T cells in the lymph node.

PMID- 23547121
TI  - Critical care nurse readers: our inspiration and design driving force.

PMID- 23547122
TI  - Alteplase treatment of acute pulmonary embolism in the intensive care unit.
AB  - Acute pulmonary embolism accounts for 50 000 to 100 000 deaths each year in the
      United States. Because of the wide spectrum of clinical manifestations, ranging
      from massive pulmonary embolism to small peripheral emboli, stratifying and
      treating patients according to their signs and symptoms is important when an
      acute embolism is suspected. Patients' clinical findings can range from no signs
      or symptoms to unstable hemodynamic status and shock. The 3-month mortality is
      10% to 15%, but can be as high as 60% in patients with hemodynamic shock. This
      article reviews the classifications of acute peripheral emboli, explains the
      treatment of acute peripheral emboli, reviews the pharmacology of alteplase, and
      presents an assessment of the literature evaluating alteplase for the treatment
      of acute peripheral emboli. Clinical pearls for the administration, monitoring,
      and care of a patient receiving alteplase in an intensive care unit also are
      discussed.

PMID- 23547123
TI  - Putting evidence into nursing practice: four traditional practices not supported
      by the evidence.
AB  - Evidence-based nursing practice is essential to the delivery of high-quality care
      that optimizes patients' outcomes. Studies continue to show improved outcomes
      when best evidence is used in the delivery of patient care. Despite awareness of
      the importance of practicing by using best evidence, achieving and sustaining
      evidence-based practice within practice environments can be challenging, and
      research suggests that integration of evidence-based practice into daily clinical
      practice remains inconsistent. This article addresses 4 practice issues that,
      first, are within the realm of nursing and if changed might improve care of
      patients and, second, are areas in which the tradition and the evidence do not
      agree and practice continues to follow tradition. The topics addressed are (1)
      noninvasive measurement of blood pressure in children, (2) oxygen administration
      for patients with chronic obstructive pulmonary disease, (3) intravenous catheter
      size and blood administration, and (4) infection control practices to prevent
      infections. The related beliefs, current evidence, and recommendations for
      practice related to each topic are described.

PMID- 23547125
TI  - Pharmacological considerations in human immunodeficiency virus-infected adults in
      the intensive care unit.
AB  - According to estimates, 1.2 million Americans are infected with human immuno
      deficiency virus (HIV). Because of antiretroviral therapy, persons who have HIV
      infection or have progressed to AIDS are living longer. As a result, the
      likelihood that they will need critical care nursing is increasing. Unlike in
      years past, when these patients were often admitted because of the consequences
      of immunosuppression, today they are also being cared for in critical care units
      for other conditions associated with aging, other chronic health conditions, and
      trauma. When persons who have HIV disease or AIDS are admitted to the intensive
      care unit, nurses must be prepared to provide care, especially management of
      complexities associated with antiretroviral therapy. Therefore, this article
      examines critical care nurses' role in initiating and administering
      antiretroviral therapy in the intensive care unit and reducing the risk of drug
      interactions associated with the therapy.

PMID- 23547127
TI  - Aortic stenosis: pathophysiology, diagnosis, and medical management of
      nonsurgical patients.
AB  - As the average lifespan continues to increase, nurses are managing more patients
      with aortic stenosis. When an asymptomatic patient begins to manifest signs and
      symptoms due to progressive narrowing and stiffening of the aortic valve, the
      only effective therapy is surgical replacement of the valve. But, some patients
      cannot undergo or do not opt for surgery. Nurses are challenged by the tenuous
      balance between the narrow range of preload and afterload to maintain forward
      blood flow and adequate cardiac output in patients with severe aortic stenosis.
      Understanding the complex normal anatomy and physiology of the aortic valve can
      help nurses appreciate the consequences of this type of stenosis. Nursing care
      for patients with aortic stenosis requires advanced skills in patient assessment
      and an appreciation of the hemodynamic responses to activities of daily living
      and to nursing interventions such as administration of medications.

PMID- 23547128
TI  - Inequity of patient assignments: fact or fiction?
AB  - The leadership group of the medical/surgical intensive care unit at Children's
      Hospital Boston, working within the healthy work environment guidelines of the
      American Association for Critical-Care Nurses, heard that some staff nurses
      thought that their patient care assignments were unfair; specifically, certain
      nurses always received a single assignment while other nurses always received a
      double assignment. The nurses' concerns were validated and addressed, and unit
      leaders continue to monitor the nurses' concerns, which has resulted in more
      equitable assignments. Acknowledging the concerns of staff nurses is a positive
      first step in maintaining a healthy work environment. Staff nurses' voices were
      heard, and their voices resulted in a positive change in the unit that embraced a
      healthy work environment and supported patient care.

PMID- 23547129
TI  - Neurologic assessment after fibrinolytic therapy for myocardial infarction.

PMID- 23547130
TI  - Practice makes perfect.

PMID- 23547131
TI  - A pediatric critical care practice group: use of expertise and evidence-based
      practice in identifying and establishing "best" practice.

PMID- 23547133
TI  - I am a critical care nurse.

PMID- 23547134
TI  - Working memory coding of analog stimulus properties in the human prefrontal
      cortex.
AB  - Building on evidence for working memory (WM) coding of vibrotactile frequency
      information in monkey prefrontal cortex, recent electroencephalography studies
      found frequency processing in human WM to be reflected by quantitative
      modulations of prefrontal upper beta activity (20-30 Hz) as a function of the to
      be-maintained stimulus attribute. This kind of stimulus-dependent activity has
      been observed across different sensory modalities, suggesting a generalized role
      of prefrontal beta during abstract WM processing of quantitative magnitude
      information. However, until now the available empirical evidence for such
      quantitative WM representation remains critically limited to the retention of
      periodic stimulus frequencies. In the present experiment, we used retrospective
      cueing to examine the quantitative WM processing of stationary (intensity) and
      temporal (duration) attributes of a previously presented tactile stimulus. We
      found parametric modulations of prefrontal beta activity during cued WM
      processing of each type of quantitative information, in a very similar manner as
      had before been observed only for periodic frequency information. In particular,
      delayed prefrontal beta modulations systematically reflected the magnitude of the
      retrospectively selected stimulus attribute and were functionally linked to
      successful behavioral task performance. Together, these findings converge on a
      generalized role of stimulus-dependent prefrontal beta-band oscillations during
      abstract scaling of analog quantity information in human WM.

PMID- 23547135
TI  - Whole-brain mapping of structural connectivity in infants reveals altered
      connection strength associated with growth and preterm birth.
AB  - Cerebral white-matter injury is common in preterm-born infants and is associated
      with neurocognitive impairments. Identifying the pattern of connectivity changes
      in the brain following premature birth may provide a more comprehensive
      understanding of the neurobiology underlying these impairments. Here, we
      characterize whole-brain, macrostructural connectivity following preterm delivery
      and explore the influence of age and prematurity using a data-driven,
      nonsubjective analysis of diffusion magnetic resonance imaging data. T1- and T2
      weighted and -diffusion MRI were obtained between 11 and 31 months
      postconceptional age in 49 infants, born between 25 and 35 weeks postconception.
      An optimized processing pipeline, combining anatomical, and tissue segmentations
      with probabilistic diffusion tractography, was used to map mean tract anisotropy.
      White-matter tracts where connection strength was related to age of delivery or
      imaging were identified using sparse-penalized regression and stability
      selection. Older children had stronger connections in tracts predominantly
      involving frontal lobe structures. Increasing prematurity at birth was related to
      widespread reductions in connection strength in tracts involving all cortical
      lobes and several subcortical structures. This nonsubjective approach to mapping
      whole-brain connectivity detected hypothesized changes in the strength of
      intracerebral connections during development and widespread reductions in
      connectivity strength associated with premature birth. 

PMID- 23547136
TI  - Motor cortex broadly engages excitatory and inhibitory neurons in somatosensory
      barrel cortex.
AB  - Anatomical studies have shown that primary somatosensory (S1) and primary motor
      (M1) cortices are reciprocally connected. The M1 to S1 projection is thought to
      represent a modulatory signal that conveys motor-related information to S1. Here,
      we investigated M1 synaptic inputs to S1 by injecting an AAV virus containing
      channelrhodopsin-2 and a fluorescent tag into M1. Consistent with previous
      results, we found labeling of M1 axons within S1 that was most robust in the deep
      layers and in L1. Labeling was sparse in L4 and was concentrated in the
      interbarrel septa, largely avoiding barrel centers. In S1, we recorded in vitro
      from regular-spiking excitatory neurons and fast-spiking and somatostatin
      expressing inhibitory interneurons. All 3 cell types had a high probability of
      receiving direct excitatory M1 input. Both excitatory and inhibitory cells within
      L4 were the least likely to receive such input from M1. Disynaptic inhibition was
      observed frequently, indicating that M1 recruits substantial inhibition within
      S1. Additionally, a subpopulation of L6 regular-spiking excitatory neurons
      received exceptionally strong M1 input. Overall, our results suggest that
      activation of M1 evokes within S1 a bombardment of excitatory and inhibitory
      synaptic activity that could contribute in a layer-specific manner to state
      dependent changes in S1.

PMID- 23547137
TI  - Differences in intrinsic functional organization between dorsolateral prefrontal
      and posterior parietal cortex.
AB  - The dorsolateral prefrontal and posterior parietal cortex are 2 components of the
      cortical network controlling attention, working memory, and executive function.
      Little is known about how the anatomical organization of the 2 areas accounts for
      their functional specialization. In order to address this question, we examined
      the strength of intrinsic functional connectivity between neurons sampled in each
      area by means of cross-correlation analyses of simultaneous recordings from
      monkeys trained to perform working memory tasks. In both areas, effective
      connectivity declined as a function of distance between neurons. However, the
      strength of effective connectivity was higher overall and more localized over
      short distances in the posterior parietal than the prefrontal cortex. The
      difference in connectivity strength between the 2 areas could not be explained by
      differences in firing rate or selectivity for the stimuli and task events, it was
      present when the fixation period alone was analyzed, and according to simulation
      results, was consistent with a systematic difference either in the strength or in
      the relative numbers of shared inputs between neurons. Our results indicate that
      the 2 areas are characterized by unique intrinsic functional organization,
      consistent with known differences in their response patterns during working
      memory. 

PMID- 23547138
TI  - Impact of T1r3 and Trpm5 on carbohydrate preference and acceptance in C57BL/6
      mice.
AB  - Knockout (KO) mice missing the sweet taste receptor subunit T1r3 or the signaling
      protein Trpm5 have greatly attenuated sweetener preferences but learn to prefer
      sucrose in 24-h tests. Here, we examined 24-h preferences of T1r3 KO, Trpm5 KO,
      and C57BL/6J wild-type (WT) mice for glucose, fructose, galactose, and corn
      starch. Unlike glucose, fructose has little postoral reward effect in WT mice,
      whereas conflicting data have been obtained with galactose. Naive KO mice were
      initially indifferent to dilute glucose solutions (0.5-4%) but exhibited strong
      preferences for 8-32% concentrations. In a second test, they strongly preferred
      (~90%) all glucose concentrations although they drank less sugar than WT mice.
      Naive KO mice were indifferent to 0.5-8% fructose and avoided 16-32% fructose.
      However, the glucose-experienced KO mice displayed significant preferences for
      all fructose solutions. Naive KO mice preferred only 8% galactose, whereas WT
      mice preferred 4-16% galactose, and all mice avoided 32% galactose. Galactose
      experience enhanced the preference for this sugar in KO and WT mice. Naive T1r3
      KO and WT mice displayed similar preferences for 0.5-32% corn starch, which were
      enhanced by starch experience. Naive Trpm5 KO mice did not prefer starch but did
      so after 1-bottle starch experience. The results confirm the sweet taste deficits
      of T1r3 KO and Trpm5 KO mice but demonstrate their ability to develop strong
      glucose and milder galactose preferences attributed to the postoral actions of
      these sugars. The acquired preference for the non-sweet flavor properties of
      glucose generalized to those of fructose. The findings further demonstrate that
      although Trpm5 (but not T1r3) signaling is essential for starch preference, Trpm5
      KO mice can learn to prefer starch based on its postoral effects.

PMID- 23547140
TI  - Reply to Hartjen et al.

PMID- 23547139
TI  - Dissecting the mechanisms of linezolid resistance in a Drosophila melanogaster
      infection model of Staphylococcus aureus.
AB  - BACKGROUND:  Mini-host models are simple experimental systems to study host
      pathogen interactions. We adapted a Drosophila melanogaster infection model to
      evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance
      in Staphylococcus aureus. METHODS:  Fly survival was evaluated after infection
      with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal
      RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of
      CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control).
      Flies were then fed food mixed with LNZ (concentration, 15-500 ug/mL). Results
      were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and
      120 mg/kg every 12 hours. RESULTS:  LNZ at 500 ug/mL in fly food protected
      against all strains, while concentrations of 15-250 ug/mL failed to protect
      against NRS119 (survival, 1.6%-20%). An in vivo effect of cfr was only detected
      at concentrations of 30 and 15 ug/mL. In the mouse peritonitis model, LNZ (at
      doses that mimic human pharmacokinetics) protected mice from challenge with the
      cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried
      23S rRNA mutations. CONCLUSIONS:  The fly model offers promising advantages to
      dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this
      model appear to be concordant with those from the mouse peritonitis model.

PMID- 23547141
TI  - Vgamma2Vdelta2 T cells are skewed toward a terminal differentiation phenotype in
      untreated HIV infection.

PMID- 23547142
TI  - The immune response to pneumococcal polysaccharides 14 and 23F among elderly
      individuals consists predominantly of switched memory B cells.
AB  - The phenotype of B cells that respond to vaccination with the purified
      pneumococcal polysaccharide (PPS) has been a topic of debate. We have recently
      identified the phenotype of cells from healthy young volunteers as CD27(+)IgM(+)
      B cells. However, the PPS-responding B-cell population has not yet been
      identified in high-risk populations, such as elderly individuals. Previous
      studies have shown that elderly individuals have a lower percentage of
      immunoglobulin M memory B cells than healthy young adults. In this study, we
      directly characterized the phenotype of PPS-specific B cells before and after
      vaccination with PPS vaccine (PPV) in elderly adults, using fluorescently labeled
      PPS14 and PPS23F. In contrast to our observations in healthy young volunteers,
      the PPS-responding B-cell population consisted primarily of switched memory
      (CD27(+)IgM(-)) B cells. In concurrence with these findings, postvaccination
      immunoglobulin M concentrations were not significantly increased in this
      population, and the opsonophagocytic response was decreased, compared with that
      in young adults. These findings identify a significant shift in the phenotype of
      the B-cell population in response to PPV among elderly individuals.

PMID- 23547143
TI  - Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with
      leprosy risk and regulates immune activation during mycobacterial infection.
AB  - Conflicting findings about the association between leprosy and TLR1 variants
      N248S and I602S have been reported. Here, we performed case-control and family
      based studies, followed by replication in 2 case-control populations from Brazil,
      involving 3162 individuals. Results indicated an association between TLR1 248S
      and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P =
      .004) and the family based study (z = 2.02; P = .05). This association was
      consistently replicated in other populations (combined OR, 1.51; P < .001),
      corroborating the finding that 248S is a susceptibility factor for leprosy.
      Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs)
      carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when
      stimulated with Mycobacterium leprae but not with lipopolysaccharide or
      PAM3cysK4. The same effect was observed after infection of PBMCs with the Moreau
      strain of bacillus Calmette-Guerin but not after infection with other strains.
      Finally, molecular dynamics simulations indicated that the Toll-like receptor 1
      structure containing 248S amino acid is different from the structure containing
      248N. Our results suggest that TLR1 248S is associated with an increased risk for
      leprosy, consistent with its hypoimmune regulatory function.

PMID- 23547144
TI  - Oral administration of carbonic anhydrase I ameliorates murine experimental
      colitis induced by Foxp3-CD4+CD25- T cells.
AB  - IBDs are thought to involve uncontrolled innate and adaptive immunity against
      intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal
      bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD.
      We show here that oral tolerization to CA I induced antigen-specific protection
      from intestinal inflammation in a murine model. Oral administration of CA I but
      not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine
      colitis and DSS-induced murine colitis. Next, we investigated the mechanisms
      involved in the therapeutic effects of oral administration, such as induction of
      ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation
      of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN
      and colon. When compared with PBS-treated mice, CA I-treated mice had higher
      Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon;
      had higher TGF-beta production in the MLN and colon; had lower RORgammat mRNA
      expression in the MLN and colon; and had lower IL-17 mRNA expression and
      production in the MLN. These results demonstrate that oral administration of CA I
      induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+)
      Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that
      oral tolerization with CA I is an effective therapeutic strategy for IBD
      regulation.

PMID- 23547145
TI  - Calcium-sensitive mini- and microelectrodes.
AB  - It is widely agreed that the best method for measuring the ionized free calcium
      concentration ([Ca(2+)]) in large volumes of biological solutions is to use
      Ca(2+)-sensitive macroelectrodes. These are commercially available. To measure
      [Ca(2+)] in small volumes of solution, minielectrodes with 1-2-mm tips can easily
      be made and used, and may also be commercially available. Ca(2+)-sensitive
      microelectrodes (CaSMs, with 0.5-2-MUm tips) can also be made and used
      extracellularly or intracellularly in robust cells, but interest in their use has
      recently been largely eclipsed. This is because of practical difficulties and the
      introduction of a large number of fluorescent and other optical calcium probes
      with calcium sensitivities varying from the nanomolar to the millimolar range,
      such as Fura-2, Indo-1, Fluo-4, and many others. In this article, we emphasize
      the utility of Ca(2+)-selective electrodes and show that their use is
      complementary to use of fluorescent and other optical methods. Each method has
      advantages and disadvantages. Because numerous reviews and books have been
      dedicated to the theoretical aspects of ion-selective electrode principles and
      technology, this article is mainly intended for investigators who have some
      degree of electrophysiological experience with ion-selective electrodes or
      microelectrodes.

PMID- 23547146
TI  - Purification and culture of spinal motor neurons.
AB  - Motor neurons are responsible for voluntary movement. Lower motor neurons are
      characterized by large soma, the potential to form very long axons, and wide
      ranging dendritic arborization. They receive direction from various neuronal cell
      types and induce movement of skeletal muscle fibers through acetylcholine release
      at the neuromuscular junction. Each lower motor neuron can communicate with 10 to
      several hundred muscle fibers at firing rates modulated by the balance of ongoing
      neurotransmitter signaling. Disease and trauma that affect lower motor neurons
      can cause paralysis and, in some cases, death. Studies using primary cultures of
      these cells have ongoing potential to facilitate a deeper understanding of their
      biology and function.

PMID- 23547147
TI  - Octodon degus (Molina 1782): a model in comparative biology and biomedicine.
AB  - One major goal of integrative and comparative biology is to understand and
      explain the interaction between the performance and behavior of animals in their
      natural environment. The Caviomorph, Octodon degu, is a native rodent species
      from Chile, and represents a unique model to study physiological and behavioral
      traits, including cognitive and sensory abilities. Degus live in colonies and
      have a well-structured social organization, with a mostly diurnal-crepuscular
      circadian activity pattern. More notable is the fact that in captivity, they
      reproduce and live between 5 and 7 yr and show hallmarks of neurodegenerative
      diseases (including Alzheimer's disease), diabetes, and cancer.

PMID- 23547148
TI  - Clonal analysis of olfaction in Drosophila: generation of flies with mosaic
      labeling.
AB  - Clonal analysis with the MARCM (mosaic analysis with a repressible cell marker)
      system can be used for studying cell lineage, development, and anatomy in the
      Drosophila olfactory system and other parts of the fly brain. This protocol gives
      a method for generating flies with mosaic labeling. It describes how to establish
      a mating cage for MARCM in PNs (projection neurons) of the fly antennal lobe and
      then select appropriate flies for dissection and staining using
      immunohistochemistry. The protocol can be adapted to determine the birth order of
      neuroblast lineages or individual cells. Alternatively, it can be used to dissect
      a complicated Gal4 line into its component neuroblast lineages to help elucidate
      projection patterns and connectivity. Collecting newly hatched larvae during a
      short time window allows for precise control of the stage during development at
      which the heat shock is applied.

PMID- 23547149
TI  - Clonal analysis of olfaction in Drosophila: immunochemistry and imaging of fly
      brains.
AB  - Clonal analysis with the MARCM (mosaic analysis with a repressible cell marker)
      system can be used for studying cell lineage, development, and anatomy in the
      Drosophila olfactory system and other parts of the fly brain. This protocol
      describes the dissection, staining, and imaging of brains from Drosophila with
      mosaic labeling. Staining for the presynaptic marker Bruchpilot (nc82) is
      performed in the example given here. The well-stained whole brain images that are
      obtained can be used to examine neuronal morphology. They are of sufficient
      quality to be used for image registration, which allows one to compare confocal
      images of labeled neurons in different brains.

PMID- 23547150
TI  - Clonal analysis of olfaction in Drosophila: image registration.
AB  - Clonal analysis with the MARCM (mosaic analysis with a repressible cell marker)
      system can be used for studying cell lineage, development, and anatomy in the
      Drosophila olfactory system and other parts of the fly brain. To compare confocal
      images of labeled neurons in different brains, it may be desirable to register
      them to a template or standard brain. There are various image registration
      approaches available. Some depend on manually specifying landmarks on the brains
      to be registered. Others depend only on the grayscale intensity value of one of
      the channels in the confocal image. Another important difference between
      registration approaches is whether they apply linear or nonlinear (warping)
      transformations. Linear transformations typically include translation, rotation,
      and scaling along each axis. Nonlinear transformations are much more
      computationally intensive, but are required to register brains with different
      shapes. Here we describe the practical steps required for an intensity-based
      nonlinear registration that has been used to map the higher olfactory centers of
      the Drosophila brain using the staining for the presynaptic marker Bruchpilot
      (nc82). This registration is in fact a two-step process. The first step is a
      linear transformation that roughly aligns the two brains, followed by a second
      nonlinear step that allows different parts of the brain to move in slightly
      different directions.

PMID- 23547151
TI  - Getting started in stereology.
AB  - Stereology involves sampling structural features in sections of tissue with
      geometrical probes. This article discusses some practical issues that must be
      dealt with when getting started in stereology, including tissue preparation
      methods and determining how many tissue sections and probes are needed to make a
      stereological estimate.

PMID- 23547152
TI  - RNA structure determination using nuclease digestion.
AB  - Determining RNA structures (i.e., single- and double-strand regions) is often
      useful when assessing the potential for certain RNAs to interact with proteins or
      when determining whether RNAs that are dissimilar in sequence can form the same
      structure. A number of ribonucleases (RNases) have been used to map RNA
      structure, but many of these are no longer available. However, three commonly
      available RNA endonucleases (RNase T1, RNase I, and RNase V1) can provide a
      wealth of structural information. Cleavages of end-labeled RNA are initiated by
      one of the RNases (H2O is used for mock-treated controls), terminated with
      aurintricarboxylic acid (a potent RNase inhibitor), and detected by
      electrophoresis on denaturing polyacrylamide gels. Because there are enzymes that
      can cleave only when the RNA is single stranded (e.g., RNase T1) or double
      stranded (e.g., RNase V1), it is possible to do parallel analyses.

PMID- 23547153
TI  - How to make calcium-sensitive minielectrodes.
AB  - In this protocol we describe how to make and use minielectrodes for measuring
      [Ca(2+)] in small volumes of solution. The minielectrodes are ~2 mm in diameter
      and have sufficiently low resistances to be used with a standard pH meter. They
      are made by dipping polyethylene or borosilicate glass tubes (~5 cm long) in a
      membrane solution. Although the chemicals used to make these Ca(2+)-sensitive
      minielectrodes are expensive, they can be used to make hundreds of electrodes,
      each with a useful life of several months.

PMID- 23547154
TI  - How to make calcium-sensitive microelectrodes.
AB  - Ca(2+)-sensitive microelectrodes (CaSMs) directly measure the pCa at their tip,
      which can be in a small extracellular space or inside a large and robust cell.
      They do not add to buffering and do not require expensive equipment. But they are
      time-consuming to make, require a reference electrode in the same location, and
      tend to create a leak around the point of insertion. In addition, CaSMs only work
      well with a tip diameter of >1 MUm. In this protocol, we describe how to make and
      use the electrodes and briefly consider possible problems.

PMID- 23547155
TI  - Husbandry and breeding in the Octodon degu (Molina 1782).
AB  - The Octodon degu is a native rodent species from South America, which lives in
      colonies with a well-structured social organization grouping of 5-10 young and 2
      5 adult animals sharing a burrow system. They show a temperature-dependent
      diurnal-crepuscular activity pattern. In nature they rarely survive 2 yr, mostly
      because of predation. However, in captivity, females reproduce for 4-4.5 yr, and
      both sexes live for 5-7 yr. Males remain fertile until death. Some care is
      required to maintain healthy degus, particularly breeding females. Here we
      describe husbandry and breeding guidelines from the experience of the University
      of Michigan degu colony. With the husbandry practices described here, 90% of pups
      born in our colony reach maturity (6 mo of age), and no diarrheal diseases are
      apparent in our adult population.

PMID- 23547156
TI  - All-optical in situ histology of brain tissue with femtosecond laser pulses.
AB  - This protocol describes the application of laser pulses to image and ablate
      neuronal tissue for the purpose of automated histology. The histology is
      accomplished in situ using serial two-photon imaging of labeled tissue and
      removal of the imaged tissue with amplified, femtosecond pulses. Together with
      the use of endogenous fluorescent indicators and/or deep penetration of antibody
      labels and organic dyes, this method may be used to automatically image,
      reconstruct, and vectorize structures of interest across millimeter to centimeter
      regions of brain with micrometer resolution.

PMID- 23547157
TI  - Preparation and use of reporter constructs for imaging morphogenesis in Xenopus
      embryos.
AB  - To understand dynamic cell and tissue mechanics during Xenopus laevis
      morphogenesis requires the use of live reporters of cell architecture as well as
      reporters for the location and activity of proteins in cells within a
      multicellular tissue. Fluorescently tagged proteins are some of the most useful
      reporters for live cell work. These fluorescent reporters are either proteins
      conjugated to small fluorochromes or molecularly engineered chimeric fluorescent
      proteins, and they can be distributed evenly across a tissue or localized within
      a subset of cells. An evenly distributed reporter is useful when visualizing
      patterns of protein localization within a field of cells. Alternatively,
      restricting the expression of a reporter to single cells or patches of cells in a
      mosaic can reveal patterns of subcellular localization. Here we discuss methods
      for synthesizing mRNA encoding fluorescent proteins and for expressing these
      proteins evenly as well as in scattered populations within a multicellular
      tissue.

PMID- 23547158
TI  - Microsurgical approaches to isolate tissues from Xenopus embryos for imaging
      morphogenesis.
AB  - To understand dynamic cell and tissue mechanics during Xenopus laevis
      morphogenesis requires the use of live reporters of cell architecture as well as
      reporters for the location and activity of proteins in cells within a
      multicellular tissue. Fluorescently tagged proteins are some of the most useful
      reporters for live cell work. Once the desired expression pattern of fluorescent
      reporters has been found, the next step is preparing samples of tissue explants
      to bring subcellular structures and protein dynamics within the range of high
      numerical aperture (NA) objectives. Visualization of dynamic living structures
      like the cytoskeleton requires the use of high-resolution confocal microscopes
      outfitted with oil-immersion, high-NA objectives. These objectives, typically
      40*, 63*, and 100*, have very short working distances (i.e., samples must be
      brought within 150 MUm of the coverslip, but perform optimally only when samples
      are <25 MUm from the coverslip). Thus, to visualize protein dynamics and follow
      cell behaviors during morphogenetic events, tissues must be isolated by
      microsurgery and cultured on the glass surface of custom-made culture chambers.
      To visualize multicellular tissues from Xenopus embryos, we microsurgically
      dissect tissues from the desired part of the embryo using fine tools made from
      human hair. In this protocol, we discuss tools, microsurgery technique, and
      specific surgical manipulations to isolate important tissues from the
      gastrulating embryo.

PMID- 23547159
TI  - Assembly of chambers for stable long-term imaging of live Xenopus tissue.
AB  - Understanding the molecular mechanisms and cellular mechanics that drive
      morphogenesis in Xenopus laevis embryos requires high-resolution quantitative
      imaging of cell movement and protein dynamics within multicellular tissues. To
      perform long-term tissue culture and stable imaging of live Xenopus tissue, we
      have developed a simple acrylic chamber that can be sealed and reused. The
      explants can be cultured on an adhesive substrate or within a nonadhesive
      microenvironment. We have developed a method for sandwiching isolated marginal
      zone (MZ) explants between thin agarose sheets. To manipulate the stiffness of
      the substrate or to measure cell traction generated by cells in an intact tissue,
      a fibronectin-conjugated polyacrylamide gel (FN-PAG) substrate can be used. The
      mechanical properties of this substrate can be easily modulated by varying the
      ratio of acrylamide to bis-acrylamide and the transparent nature of the PAG can
      allow observation of intracellular dynamics through the gel. Cell tractions are
      detected by following movements of fluorescent beads embedded in the gel.

PMID- 23547160
TI  - Investigating morphogenesis in Xenopus embryos: imaging strategies, processing,
      and analysis.
AB  - Methods have been developed for visualizing cell movement and protein dynamics
      during morphogenesis within live multicellular tissues isolated from Xenopus
      laevis embryos. These include the preparation and use of reporter constructs in
      Xenopus embryos, microsurgical techniques for isolating embryonic tissues, and
      methods for culturing live tissues for extended periods. In this article, we
      present strategies for successful imaging of large thick embryonic tissues by
      improving the signal and minimizing damage to cells and tissues from
      overexposure. We also describe strategies for image analysis, including
      construction of kymographs, use of time- and z-projected confocal stacks, and
      approaches to segment images using regions of interest. With these imaging tools,
      the "cut-and-paste" embryology of the Xenopus model system allows remarkable
      access to both the mechanics of cells and tissues as well as the complex cell
      biology of adhesion and the cytoskeleton during morphogenesis.

PMID- 23547161
TI  - Measuring angiogenesis and hemodynamics in mice.
AB  - This protocol outlines methods to measure vascular parameters, including
      angiogenesis (e.g., vascular density, length, diameter) and hemodynamics (e.g.,
      erythrocyte velocity), in tumors and normal vascular networks in mice.
      Fluorescein-isothiocyanate (FITC)-dextran is injected into the tail vein of mice
      to visualize microvessels within 150 MUm (using single-photon microscopy) or ~600
      MUm (using multiphoton laser-scanning microscopy [MPLSM]) of a tumor/window
      interface. Randomly selected areas (three to six locations/tumor or animal) are
      investigated using long-working-distance objectives with appropriate
      magnification. During each observation period, FITC-fluorescence images are
      recorded for 60 sec, and the videotapes are analyzed off-line for single-photon
      microscopy; or a three-dimensional (3D) image stack of the vessel network is
      generated, and vessel properties are measured for MPLSM. If desired, red blood
      cell (RBC) flux can be measured on a vessel-by-vessel basis using fluorescent
      tracer RBCs.

PMID- 23547162
TI  - Purification and culture of spinal motor neurons from rat embryos.
AB  - We describe an immunopanning protocol to isolate, enrich, and culture spinal
      motor neurons from rat embryonic spinal cords. The method takes advantage of
      several distinct properties of rat lower motor neurons to isolate them from
      neighboring cells. First, an ideal stage in development after motor neurons are
      born (embryonic day 14 during rat gestation), but prior to extensive axonal
      extension or developmental apoptosis, is exploited. Lower motor neurons cannot be
      viably isolated using this method after birth. After dissociating embryonic
      spinal cord tissue, which contains lower motor neurons among many other cell
      types, the uniquely large motor neurons are enriched using density gradient
      centrifugation. Finally, the collected cell population is further purified based
      on selective immunopanning for motor neurons, which express the low-affinity
      nerve growth factor (NGF) receptor often referred to as p75. The near-pure lower
      motor neuron cultures are plated and seeded in defined conditions optimal for
      survival and can be maintained for several weeks. The expected yield is
      approximately 70,000 cells per embryonic spinal cord.

PMID- 23547163
TI  - To "bee or not to bee" male or female? An educational primer for use with "the Am
      tra2 gene is an essential regulator of female splice regulation at two levels of
      the sex determination hierarchy of the honeybee".
AB  - An article by Nissen et al. in the November 2012 issue of GENETICS emphasizes the
      importance of alternative splicing in the sex determination cascade of the
      honeybee Apis mellifera. This study demonstrates the application of reverse
      transcriptase PCR and RNA interference screens as genetic tools to better
      understand the regulation of transcription and splicing. It also provides the
      opportunity to explore the evolutionary origins of genes by considering the
      functions of orthologs and paralogs in different species. This Primer article
      provides background information and explanations of the concepts and findings of
      Nissen et al. and offers discussion questions for use in the classroom.

PMID- 23547166
TI  - Reply to Soman et al.

PMID- 23547167
TI  - Reply to Soman et al and Frippiat et al.

PMID- 23547168
TI  - Are prolonged/continuous infusions of beta-lactams for all?

PMID- 23547169
TI  - Is extended or continuous infusion of carbapenems the obvious solution to improve
      clinical outcomes and reduce mortality?

PMID- 23547170
TI  - A dynamic H3K27ac signature identifies VEGFA-stimulated endothelial enhancers and
      requires EP300 activity.
AB  - Histone modifications are now well-established mediators of transcriptional
      programs that distinguish cell states. However, the kinetics of histone
      modification and their role in mediating rapid, signal-responsive gene expression
      changes has been little studied on a genome-wide scale. Vascular endothelial
      growth factor A (VEGFA), a major regulator of angiogenesis, triggers changes in
      transcriptional activity of human umbilical vein endothelial cells (HUVECs).
      Here, we used chromatin immunoprecipitation followed by high-throughput
      sequencing (ChIP-seq) to measure genome-wide changes in histone H3 acetylation at
      lysine 27 (H3K27ac), a marker of active enhancers, in unstimulated HUVECs and
      HUVECs stimulated with VEGFA for 1, 4, and 12 h. We show that sites with the
      greatest H3K27ac change upon stimulation were associated tightly with EP300, a
      histone acetyltransferase. Using the variation of H3K27ac as a novel epigenetic
      signature, we identified transcriptional regulatory elements that are
      functionally linked to angiogenesis, participate in rapid VEGFA-stimulated
      changes in chromatin conformation, and mediate VEGFA-induced transcriptional
      responses. Dynamic H3K27ac deposition and associated changes in chromatin
      conformation required EP300 activity instead of altered nucleosome occupancy or
      changes in DNase I hypersensitivity. EP300 activity was also required for a
      subset of dynamic H3K27ac sites to loop into proximity of promoters. Our study
      identified thousands of endothelial, VEGFA-responsive enhancers, demonstrating
      that an epigenetic signature based on the variation of a chromatin feature is a
      productive approach to define signal-responsive genomic elements. Further, our
      study implicates global epigenetic modifications in rapid, signal-responsive
      transcriptional regulation.

PMID- 23547171
TI  - MicroRNA-150: a novel marker of left ventricular remodeling after acute
      myocardial infarction.
AB  - BACKGROUND: Left ventricular (LV) remodeling after acute myocardial infarction is
      associated with adverse prognosis. MicroRNAs (miRNAs) regulate the expression of
      several genes involved in LV remodeling. Our aim was to identify miRNAs
      associated with LV remodeling after acute myocardial infarction. METHODS AND
      RESULTS: We studied 90 patients after first ST-segment-elevation acute myocardial
      infarction. A derivation cohort consisted of 60 patients characterized by
      echocardiography predischarge and at 6-month follow-up. Thirty patients
      characterized by magnetic resonance imaging predischarge and at 4-month follow-up
      were the validation cohort. Remodeling was defined as an increase in LV end
      diastolic volume (DeltaEDV>0) between discharge and follow-up. Circulating miRNAs
      were measured by microarrays and polymerase chain reaction. Using a systems-based
      approach, we identified several miRNAs potentially involved in LV remodeling. In
      the derivation cohort, one of these miRNAs, miR-150, was downregulated in
      patients with remodeling (DeltaEDV>0) compared with patients without remodeling
      (DeltaEDV<=0). In the validation cohort, patients with remodeling had 2-fold
      lower levels of miR-150 than those without (P=0.03). miR-150 outperformed N
      terminal pro-brain natriuretic peptide to predict remodeling (area under the
      receiver-operating characteristic curve of 0.74 and 0.60, respectively). miR-150
      reclassified 54% (95% confidence interval, 5-102; P=0.03) of patients
      misclassified by N-terminal pro-brain natriuretic peptide and 59% (95% confidence
      interval, 9-108; P=0.02) of patients misclassified by a multiparameter clinical
      model, including age, sex, and admission levels of troponin I, creatine kinase,
      and N-terminal pro-brain natriuretic peptide. CONCLUSIONS: Low circulating levels
      of miR-150 are associated with LV remodeling after first ST-segment-elevation
      acute myocardial infarction. miR-150 has potential as a novel biomarker in this
      setting.

PMID- 23547164
TI  - DNA repair mechanisms and the bypass of DNA damage in Saccharomyces cerevisiae.
AB  - DNA repair mechanisms are critical for maintaining the integrity of genomic DNA,
      and their loss is associated with cancer predisposition syndromes. Studies in
      Saccharomyces cerevisiae have played a central role in elucidating the highly
      conserved mechanisms that promote eukaryotic genome stability. This review will
      focus on repair mechanisms that involve excision of a single strand from duplex
      DNA with the intact, complementary strand serving as a template to fill the
      resulting gap. These mechanisms are of two general types: those that remove
      damage from DNA and those that repair errors made during DNA synthesis. The major
      DNA-damage repair pathways are base excision repair and nucleotide excision
      repair, which, in the most simple terms, are distinguished by the extent of
      single-strand DNA removed together with the lesion. Mistakes made by DNA
      polymerases are corrected by the mismatch repair pathway, which also corrects
      mismatches generated when single strands of non-identical duplexes are exchanged
      during homologous recombination. In addition to the true repair pathways, the
      postreplication repair pathway allows lesions or structural aberrations that
      block replicative DNA polymerases to be tolerated. There are two bypass
      mechanisms: an error-free mechanism that involves a switch to an undamaged
      template for synthesis past the lesion and an error-prone mechanism that utilizes
      specialized translesion synthesis DNA polymerases to directly synthesize DNA
      across the lesion. A high level of functional redundancy exists among the
      pathways that deal with lesions, which minimizes the detrimental effects of
      endogenous and exogenous DNA damage.

PMID- 23547173
TI  - On the mini-BESTest: scoring and the reporting of total scores.

PMID- 23547172
TI  - Prevalence and predictors of ischemia and outcomes in outpatients with diabetes
      mellitus referred for single-photon emission computed tomography myocardial
      perfusion imaging.
AB  - Background- The prevalence of ischemia and its prediction of events are unclear
      in outpatients with diabetes mellitus in the modern era of intensive medical
      management. We sought to identify the prevalence of ischemia, subsequent cardiac
      events, and impact of sex, stress type, and symptom status on these findings in a
      cohort of stable outpatients with diabetes mellitus referred for single-photon
      emission computed tomography myocardial perfusion imaging (MPI). Methods and
      Results- The study cohort included 575 consecutive outpatients with diabetes
      mellitus who underwent quantitative, gated single-photon emission computed
      tomography MPI. Clinical information, stress MPI variables, and cardiac events
      were prospectively collected and analyzed. The study population was at
      intermediate risk of coronary artery disease or had known coronary artery disease
      (40.3%); 29% of patients were asymptomatic at the time of stress testing.
      Scintigraphic ischemia and significant (>=10%) left ventricular ischemia were
      present in 126 patients (21.9%) and 29 patients (5.0%), respectively, and <1% of
      patients had early revascularization. The risk of ischemia was increased >2-fold
      by male sex (P<0.001), but was not impacted by pharmacological stress (P=0.15) or
      presence of symptoms (P=0.89). During a median 4.4 years follow-up, the rate of
      cardiac death/nonfatal myocardial infarction was moderate at 2.6%/y (cardiac
      death 0.8%/y) in the total cohort, but was 5.7%/y in those with ischemia
      (P<0.001). Pharmacological stress predicted a higher cardiac event rate (P<0.001)
      but symptoms did not (P=0.55). Conclusions- This cohort of stable outpatients
      with diabetes mellitus referred for single-photon emission computed tomography
      had low rates of significant ischemia and early revascularization; an initially
      low cardiac event rate increased after 2 years. Independent predictors of cardiac
      death/nonfatal myocardial infarction were known coronary artery disease,
      pharmacological stress, and MPI ischemia. Nearly one third of those with events
      had a normal MPI, indicating a need for improved risk stratification.

PMID- 23547174
TI  - Editorial: Fat chance to enhance B cell function.

PMID- 23547175
TI  - Editorial: Triple-agent TGF-beta.

PMID- 23547176
TI  - Integrated care for management of ventricular arrhythmias: can a specialized unit
      and catheter ablation improve mortality?

PMID- 23547177
TI  - Status of cardiovascular health in US adolescents: prevalence estimates from the
      National Health and Nutrition Examination Surveys (NHANES) 2005-2010.
AB  - BACKGROUND: The American Heart Association recently developed definitions and
      metrics for monitoring the spectrum of cardiovascular health in adolescents and
      children. Current nationally representative prevalence estimates according to sex
      and race/ethnicity are unavailable. METHODS AND RESULTS: We examined the
      components of cardiovascular health in 4673 participants aged 12 to 19 years
      (representing ~33.2 million US adolescents) from the 2005-2010 National Health
      and Nutrition Examination Surveys. Population prevalence of individual
      cardiovascular health behaviors and factors was estimated according to American
      Heart Association criteria for poor, intermediate, and ideal levels. Ideal blood
      pressure was most prevalent (males, 78%; females, 90%), whereas a dramatically
      low prevalence of ideal Healthy Diet Score was observed (males, <1%; females,
      <1%). Females exhibited a lower prevalence of ideal total cholesterol (65% versus
      72%, respectively) and ideal physical activity levels (44% versus 67%,
      respectively) yet a higher prevalence of ideal blood glucose (89% versus 74%,
      respectively) compared with males. Approximately two thirds of adolescents
      exhibited ideal body mass index (males, 66%; females, 67%) and ideal smoking
      status (males, 66%; females, 70%). Less than 50% of adolescents exhibited >=5
      ideal cardiovascular health components (45%, males; 50%, females). Prevalence
      estimates according to sex were consistent across race/ethnic groups.
      CONCLUSIONS: The low prevalence of ideal cardiovascular health behaviors in US
      adolescents, particularly physical activity and dietary intake, will likely
      contribute to a worsening prevalence of obesity, hypertension,
      hypercholesterolemia, and dysglycemia as the current US adolescent population
      reaches adulthood. Population-wide emphasis on establishment of ideal
      cardiovascular health behaviors early in life is essential for maintenance of
      ideal cardiovascular health throughout the lifespan.

PMID- 23547178
TI  - Association between physician follow-up and outcomes of care after chest pain
      assessment in high-risk patients.
AB  - BACKGROUND: Assessment of chest pain is one of the most common reasons for
      emergency department visits in developed countries. Although guidelines recommend
      primary care physician (PCP) follow-up for patients who are subsequently
      discharged, little is known about the relationship between physician follow-up
      and clinical outcomes. METHODS AND RESULTS: An observational study was conducted
      on patients with higher baseline risk, defined as having diabetes mellitus or
      established cardiovascular disease, who were evaluated for chest pain,
      discharged, and without adverse clinical outcomes for 30 days in Ontario from
      2004 to 2010. Multivariable proportional hazard models were constructed to adjust
      for potential confounding between physician groups (cardiologist, PCP, or none).
      Among 56767 included patients, 17% were evaluated by cardiologists, 58% were
      evaluated by PCPs alone, and 25% had no physician follow-up. The mean age was
      66+/-15 years, and 53% were male. The highest rates of diagnostic testing,
      medical therapy, and coronary revascularization were seen among patients treated
      by cardiologists. At 1 year, the rate of death or MI was 5.5% (95% confidence
      interval, 5.0-5.9) in the cardiology group, 7.7% (95% confidence interval, 7.4
      7.9) in the PCP group, and 8.6% (95% confidence interval, 8.2-9.1) in the no
      physician group. After adjustment, cardiologist follow-up was associated with
      significantly lower adjusted hazard ratio of death or MI compared with PCP
      (hazard ratio, 0.85; 95% confidence interval, 0.78-0.92) and no physician (hazard
      ratio, 0.79; 95% confidence interval, 0.71-0.88) follow-up. CONCLUSIONS: Among
      patients with higher baseline cardiovascular risk who were discharged from the
      emergency department after evaluation for chest pain in Ontario, follow-up with a
      cardiologist was associated with a decreased risk of all-cause mortality or
      hospitalization for MI at 1 year compared with follow-up with a PCP or no
      physician follow-up.

PMID- 23547179
TI  - Effect of race and ethnicity on outcomes with drug-eluting and bare metal stents:
      results in 423 965 patients in the linked National Cardiovascular Data Registry
      and centers for Medicare & Medicaid services payer databases.
AB  - BACKGROUND: Black, Hispanic, and Asian patients have been underrepresented in
      percutaneous coronary intervention clinical trials; therefore, there are limited
      data available on outcomes for these race/ethnicity groups. METHODS AND RESULTS:
      We examined outcomes in 423 965 patients in the National Cardiovascular Data
      Registry CathPCI Registry database linked to Medicare claims for follow-up.
      Within each race/ethnicity group, we examined trends in drug-eluting stent (DES)
      use, 30-month outcomes, and relative outcomes of DES versus bare metal stents.
      Overall, 390 351 white, 20 191 black, 9342 Hispanic, and 4171 Asian patients > 65
      years of age underwent stent implantation from 2004 through 2008 at 940 National
      Cardiovascular Data Registry participating sites. Trends in adoption of DES were
      similar across all groups. Relative to whites, black and Hispanic patients
      undergoing percutaneous coronary intervention had higher long-term risks of death
      and myocardial infarction (blacks: hazard ratio, 1.28; 95% confidence interval,
      1.24-1.32; Hispanics: hazard ratio, 1.15; 95% confidence interval, 1.10-1.21).
      Long-term outcomes were similar in Asians and whites (hazard ratio, 0.99; 95%
      confidence interval, 0.92-1.08). Use of DES was associated with better 30-month
      survival and lower myocardial infarction rates compared with the use of bare
      metal stents among all race/ethnicity groups except Hispanics, who had similar
      outcomes with DES or bare metal stents. CONCLUSIONS: Black and Hispanic patients
      undergoing percutaneous coronary intervention had worse long-term outcomes
      relative to white and Asian patients. Compared with bare metal stent use, DES use
      was generally associated with superior long-term outcomes in all racial and
      ethnic groups, although these differences were not statistically significant in
      Hispanic patients.

PMID- 23547180
TI  - Social media and clinical care: ethical, professional, and social implications.

PMID- 23547181
TI  - Mechanical and electrophysiological substrate for recurrent atrial flutter
      detected by right atrial speckle tracking echocardiography and electroanatomic
      mapping in myotonic dystrophy type 1.

PMID- 23547182
TI  - Third-degree atrioventricular block in an adult with a giant cardiac fibroma.

PMID- 23547183
TI  - A patient's guide to living confidently with chronic heart failure.

PMID- 23547185
TI  - Letter by Mehta Oza and Raman regarding article, "Ischemic preconditioning for
      prevention of contrast medium-induced nephropathy: randomized pilot RenPro Trial
      (Renal Protection Trial)".

PMID- 23547186
TI  - CrossTalk proposal: TARPs modulate AMPA receptor gating transitions.

PMID- 23547187
TI  - CrossTalk opposing view: TARPs modulate AMPA receptor conformations before the
      gating transitions.

PMID- 23547190
TI  - Your ageing brain: the lows and highs of cerebral metabolism.

PMID- 23547191
TI  - I think I(CAN): modulation of TRPM4 channels may contribute not only to the
      emergence of rhythm, but robust output and metabolic sensitivity of the
      preBotzinger Complex inspiratory network.

PMID- 23547192
TI  - It takes more than one opioid receptor to inhibit a POMC neuron.

PMID- 23547193
TI  - Sweet umami: the twain shall meet.

PMID- 23547194
TI  - Computed tomography angiography for transcatheter aortic valve replacement.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an established
      alternative to surgery for patients with severe, symptomatic aortic stenosis who
      are not suitable candidates for surgical replacement of the aortic valve. The
      computed tomography (CT) technologist has a critical role in the care of patients
      undergoing TAVR. Because image acquisition and postprocessing for TAVR planning
      are highly complex, it is important for CT technologists involved in the planning
      to understand clinical detail, protocols, potential pitfalls, and factors that
      may influence workflow. PURPOSE: To describe, from the CT technologist's point of
      view, the details of CT angiography acquisition and postprocessing at 1
      institution for patients being screened for TAVR. DISCUSSION: For TAVR patients,
      CT image acquisition and postprocessing is essential for a successful
      intervention. It is clinically essential to maintain and execute a detailed,
      standardized imaging approach. CONCLUSION: TAVR planning is among the most
      complex procedures in radiology. For these patients, meticulous image acquisition
      and image postprocessing protocols are paramount, and successful patient outcomes
      depend on attention to clinical detail, protocols, potential pitfalls, and
      factors that may influence workflow.

PMID- 23547195
TI  - Ultrasonographic kidney sizes among children in Benin, Nigeria: correlation with
      age and BMI.
AB  - PURPOSE: To determine kidney sizes among Nigerian children using ultrasonography
      to provide local reference data that could be compared with renal growth charts
      when assessing kidneys of Nigerian children for growth or pathology. METHODS: The
      study design was cross-sectional and a convenience sampling technique was used to
      select a sample. Consent was obtained from participants and ethical approval was
      obtained from the local ethics committee. A DP-1100 sector scanner with a 3.5 MHz
      probe was used for the study. Sonographers measured kidney length, width, and
      thickness and calculated renal volume. Renal sizes were correlated with
      somatometric parameters. Regression equations were derived for each pair of
      variables. RESULTS: No statistically significant difference was found in kidney
      sizes between male and female participants or between length, width, or volume of
      right and left kidneys. A strong correlation was found between kidney length and
      volume and the participant's age and body mass index. CONCLUSION: This study has
      provided values of kidney sizes in a normal Nigerian pediatric population.
      Regression equations also were derived for easy computation of kidney sizes.

PMID- 23547196
TI  - What imaging teaches us about pain.
AB  - Pain diminishes the quality of life for many people, although it also may be a
      vital teacher or a warning message to be heeded. How humans process pain is a
      complicated, individualized process affected by genetics, personality, life
      experiences, and straightforward physiological processes. Imaging provides
      investigators with insight into this complicated phenomenon, and it promises to
      continue to help experts understand not only how pain is processed, but also why
      chronic pain develops in some people but not others, how we might better manage
      pain, and how pain may have played a key role in human evolution.

PMID- 23547197
TI  - Managerial strategies for creating an effective work environment.
AB  - To create a highly functioning medical imaging team, radiology managers must be
      able to analyze their departments and identify areas for improvement. This type
      of analysis means assessing front-line personnel who already work in the
      department, along with identifying staffing needs and recruiting talented new
      employees. In addition, managers must develop effective retention tools such as
      career ladders and mentorship programs to improve the overall working
      environment. This article discusses a variety of different strategies to help
      managers develop a more effective department.

PMID- 23547198
TI  - A book report.

PMID- 23547200
TI  - Distal limb radiographic technique.

PMID- 23547201
TI  - Basis of CT: the radon transform.

PMID- 23547202
TI  - Moving to an E-book curriculum in an allied health program.

PMID- 23547203
TI  - A bibliometric analysis of radiologic technology (1963-2011).

PMID- 23547204
TI  - Esophageal achalasia.

PMID- 23547205
TI  - Safety matters.

PMID- 23547206
TI  - Luke, I am your father.

PMID- 23547207
TI  - Breast calcification imaging.
AB  - Breast calcifications are a common mammographic finding, present on 86% of
      images. Although usually benign, they also can be malignant. Characteristics such
      as their size, shape, number, distribution pattern, location, density, and other
      findings help determine their pathology. The American College of Radiology's BI
      RADS assessment categories and Appropriateness Criteria guidelines help
      radiologists and other physicians determine appropriate action when
      calcifications are discovered. This article reviews breast anatomy, the
      classification of calcifications, malignant vs benign characteristics, imaging
      techniques for calcifications, and biopsy procedures.

PMID- 23547208
TI  - Trends in serious infections in rheumatoid arthritis.
AB  - OBJECTIVE: To examine trends in the rates of serious infections among patients
      diagnosed with rheumatoid arthritis (RA) in 1995-2007 compared to rates
      previously reported from the same geographical area diagnosed 1955-1994. METHODS:
      A population-based inception cohort of patients with RA in 1995-2007 was
      assembled and followed through their complete medical records until death,
      migration, or December 31, 2008. All serious infections (requiring
      hospitalization or intravenous antibiotics) were recorded. Person-year (py)
      methods were used to compare rates of infection. RESULTS: Among 464 patients with
      incident RA in 1995-2007, 54 had >= 1 serious infection (178 total). These were
      compared to 609 patients with incident RA in 1955-1994 (290 experienced >= 1
      serious infection; 740 total). The rate of serious infections declined from 9.6
      per 100 py in the 1955-1994 cohort to 6.6 per 100 py in the 1995-2007 cohort.
      Serious gastrointestinal (GI) infection rates increased from 0.5 per 100 py in
      the 1955-1994 cohort to 1.25 per 100 py in the 1995-2007 cohort. Among patients
      with a history of serious infection, the rate of subsequent infection increased
      from 16.5 per 100 py in 1955-1994 to 37.4 per 100 py in 1995-2007. There was an
      increase in the rate of serious infections in patients who received biologic
      agents, but this did not reach significance. CONCLUSION: Aside from GI
      infections, the rate of serious infections in patients with RA has declined in
      recent years. However, the rate of subsequent infections was higher in recent
      years than previously reported.

PMID- 23547209
TI  - Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase
      II, randomized, double-blind, placebo-controlled, dose-ranging Study.
AB  - OBJECTIVE: To evaluate the efficacy/safety of belimumab in patients with
      rheumatoid arthritis (RA). METHODS: Patients fulfilling American College of
      Rheumatology (ACR) criteria for RA for >= 1 year who had at least moderate
      disease activity while receiving stable disease-modifying antirheumatic drug
      (DMARD) therapy and failed >= 1 DMARD were randomly assigned to placebo or
      belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28,
      and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional
      24-week extension (n = 237) in which all patients received belimumab. Primary
      efficacy endpoint was the Week 24 ACR20 response. RESULTS: Week 24 ACR20
      responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p =
      0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking
      any belimumab dose who continued with belimumab in the open-label extension had
      an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks
      was seen in patients taking placebo who switched in the extension to belimumab 10
      mg/kg. Greater response rates were observed in patients who at baseline were
      rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor
      necrosis factor inhibitor-naive, or had elevated C-reactive protein levels,
      Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858
      ng/ml). Adverse event rates were similar across treatment groups. CONCLUSION: In
      this phase II trial, belimumab demonstrated efficacy and was generally well
      tolerated in patients with RA who had failed previous therapies.
      [ClinicalTrials.gov identifier NCT00071812].

PMID- 23547210
TI  - Etanercept improves lipid profile and oxidative stress measures in patients with
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the effect of 1-year treatment with the anti-tumor
      necrosis factor-alpha (TNF-alpha) drug etanercept on lipid profile and oxidative
      stress in children and adolescents with juvenile idiopathic arthritis (JIA).
      METHODS: Thirty children with JIA (22 females; mean age 12.3 +/- SD 5.7 yrs), all
      eligible for anti-TNF-alpha treatment, were assessed at baseline and after 6- and
      12-month treatment with etanercept. Disease activity was determined using the
      Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to
      measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-alpha,
      interleukin-1beta (IL-1beta), IL-6 and interferon-gamma. To measure the oxidative
      stress marker 8-iso-prostaglandin F2alpha, 24-h urine samples were collected.
      RESULTS: Inflammatory indicators (CRP and ESR) and JADAS scores improved
      significantly after 1 year of etanercept treatment (all p < 0.001).
      Proinflammatory cytokines showed significant reduction during the study period
      (all p < 0.001). Similar reductions were detected in total cholesterol (p <
      0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p <
      0.001), whereas no significant change was found in high-density lipoprotein
      cholesterol. No side effects were observed during the treatment period.
      CONCLUSION: This study shows for the first time that anti-TNF-alpha therapy for
      JIA is associated not only with a beneficial effect on clinical disease activity
      and inflammatory indexes, but also with improved lipid profile and oxidative
      stress. These findings suggest that TNF-alpha blockers might reduce
      atherosclerotic risk in children with JIA.

PMID- 23547211
TI  - Cardiovascular events are not associated with MTHFR polymorphisms, but are
      associated with methotrexate use and traditional risk factors in US veterans with
      rheumatoid arthritis.
AB  - OBJECTIVE: C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate
      reductase (MTHFR) have been associated with increased cardiovascular (CV) events
      in non-rheumatoid arthritis (RA) populations. We investigated potential
      associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV
      event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry.
      METHODS: VARA participants were genotyped for MTHFR polymorphisms. Variables
      included demographic information, baseline comorbidities, RA duration,
      autoantibody status, and disease activity. Patients' comorbidities and outcome
      variables were defined using International Classification of Diseases-9 and
      Current Procedural Terminology codes. The combined CV event outcome included
      myocardial infarction (MI), percutaneous coronary intervention, coronary artery
      bypass graft surgery, and stroke. Cox proportional hazards regression was used to
      model the time-to-CV event. RESULTS: Data were available for 1047 subjects. Post
      enrollment CV events occurred in 97 patients (9.26%). Although there was a trend
      toward reduced risk of CV events, MTHFR polymorphisms were not significantly
      associated with time-to-CV event. Time-to-CV event was associated with prior
      stroke (HR 2.01, 95% CI 1.03-3.90), prior MI (HR 1.70, 95% CI 1.06-2.71),
      hyperlipidemia (HR 1.57, 95% CI 1.01-2.43), and increased modified Charlson-Deyo
      index (HR 1.23, 95% CI 1.13-1.34). MTX use (HR 0.66, 95% CI 0.44-0.99) and
      increasing education (HR 0.87, 95% CI 0.80-0.95) were associated with a lower
      risk for CV events. CONCLUSION: Although MTHFR polymorphisms were previously
      associated with CV events in non-RA populations, we found only a trend toward
      decreased association with CV events in RA. Traditional risk factors conferred
      substantial CV risk, while MTX use and increasing years of education were
      protective.

PMID- 23547212
TI  - Early local swelling and tenderness are associated with large-joint damage after
      8 years of treatment to target in patients with recent-onset rheumatoid
      arthritis.
AB  - OBJECTIVE: To assess whether early swelling and tenderness in large joints in
      patients with rheumatoid arthritis (RA) is predictive of later local damage and
      whether this leads to functional disability. METHODS: Two-year clinical and 8
      year radiological followup data from the BeSt study (trial numbers NTR262 and
      NTR265), a randomized controlled treat-to-target trial, were used. The
      association between early local joint swelling and/or tenderness (at least once,
      or for >= 2 consecutive visits) and later large-joint damage (Larsen score >= 1)
      was assessed using generalized estimating equations. The association between
      large-joint damage and functional ability [by Health Assessment Questionnaire
      (HAQ)] was assessed using logistic and linear regression analysis. RESULTS:
      Clinical and 8-year radiological data were available for 290 patients.
      Concomitant local joint swelling and tenderness at least once in the first 2
      years was independently associated with damage of the large joints (OR 2.5, 95%
      CI 1.7-3.6), as was swelling without tenderness (OR 2.0, 95% CI 1.1-3.6).
      Stronger effects were seen for persistent swelling and/or tenderness. Other
      independent predictors for joint damage were baseline erythrocyte sedimentation
      rate (OR 1.01, 95% CI 1.01-1.02) and the presence of rheumatoid factor and/or
      anticitrullinated protein antibodies (OR 2.5, 95% CI 1.5-4.1; and OR 2.2, 95% CI
      1.3-3.8, respectively). Patients with large-joint damage had a higher HAQ score
      after 8 years than patients without (difference 0.15). CONCLUSION: Early local
      swelling and tenderness are independent predictors of later joint damage in these
      joints after 8 years of Disease Activity Score-guided treatment in patients with
      RA. This suggests that suppression of local inflammation could help prevent local
      damage and functional disability.

PMID- 23547213
TI  - Patterns and associated risk of perioperative use of anti-tumor necrosis factor
      in patients with rheumatoid arthritis undergoing total knee replacement.
AB  - OBJECTIVE: The patterns and risks of perioperative use of anti-tumor necrosis
      factor (anti-TNF) medication in patients with rheumatoid arthritis (RA) are not
      well studied. We examined the patterns of perioperative anti-TNF use and risk of
      postoperative adverse events (AE) in patients undergoing total knee replacement
      (TKR). METHOD: Retrospective cohort study with followup. RA cases within a TKR
      registry were identified by ICD-9 code (714.0) or self-report. Mailed
      questionnaires queried anti-TNF use and duration of RA. AE were determined by
      chart review and patient self-report, and included surgical site infection,
      pulmonary embolus, deep venous thrombosis, pneumonia, and any infection or re
      operation within 6 months. RESULTS: There were 268 TKR cases with RA. The stop
      time for anti-TNF preoperatively correlated with dosing schedule; restart time
      was after wound healing. There were 7 surgical site infections (3%), one (0.4%)
      of which was a deep joint infection in bilateral TKA requiring explant. The anti
      TNF group had 3.26% (3/92) local site infection versus 2.10% (3/143) in the group
      without anti-TNF and this difference was not statistically significant (Fisher
      exact test, p = 0.68). The one deep joint infection was in the anti-TNF group.
      Six-month AE rate was 7.61% in the anti-TNF group versus 6.99% in the group
      without anti-TNF (Fisher exact test, p = 1.0). CONCLUSION: There was a low risk
      of infection and perioperative adverse events in patients with RA receiving anti
      TNF therapy who were undergoing TKR. This raises the question whether it is
      necessary to stop anti-TNF for a long period prior to surgery. Given the possible
      risks associated with stopping anti-TNF, including worsening of disease, further
      study is needed to determine optimal perioperative use of anti-TNF among patients
      with RA undergoing TKR.

PMID- 23547214
TI  - Expression of peroxisome proliferator-activated receptors alpha, beta, gamma, and
      H- and L-prostaglandin D synthase during osteoarthritis in the spontaneous
      hartley guinea pig and experimental dog models.
AB  - OBJECTIVE: To investigate the expression of peroxisome proliferator-activated
      receptors (PPAR) alpha, beta, and gamma, and hematopoietic and lipocalin-type
      prostaglandin D synthase (H- and L-PGDS) over the course of osteoarthritis (OA)
      in the spontaneous Hartley guinea pig and the anterior cruciate ligament
      transection dog models. METHODS: Guinea pigs were sacrificed at 2 (control
      group), 4, 8, and 12 months of age (n = 5 per group). Non-operated (control) and
      operated dogs were sacrificed at 4, 8, and 12 weeks postsurgery. Cartilage was
      evaluated histologically using the Osteoarthritis Research Society International
      (OARSI) guidelines. The expression of PPAR-alpha, beta, gamma, and H- and L-PGDS
      was evaluated by real-time PCR and immunohistochemistry. The nonparametric
      Spearman test was used for correlation analysis. RESULTS: PPAR-alpha, beta, and
      gamma were detected in medial tibial plateau from control animals in both the
      spontaneous and surgical models. Levels of PPAR-alpha and beta did not change
      over the course of OA, whereas PPAR-gamma levels decreased during progression of
      disease. We also observed that the expression of H-PGDS remained unchanged,
      whereas L-PGDS increased over the course of OA. PPAR-gamma levels correlated
      negatively, whereas L-PGDS levels correlated positively, with the histological
      score of OA. CONCLUSION: The level of PPAR-gamma decreased, whereas level of L
      PGDS increased during the progression of OA. These data suggest that reduced
      expression of PPAR-gamma may contribute to the pathogenesis of OA, whereas
      enhanced expression of L-PGDS may be part of a reparative process.

PMID- 23547215
TI  - Association of gastroesophageal factors and worsening of forced vital capacity in
      systemic sclerosis.
AB  - OBJECTIVE: Interstitial lung disease (ILD) is a common complication of systemic
      sclerosis (SSc) and causes death. Once lung fibrosis occurs, disease course may
      become stable or decline. Little is known about risks for progression. We studied
      SSc-gastroesophageal (GE) involvement in relation to worsening forced vital
      capacity (FVC) on pulmonary function tests (PFT) to investigate whether it was
      related to progression. Our objective was to determine whether GE reflux and
      dysphagia are associated with progressive moderate/severe ILD as measured by PFT
      over 3 years. METHODS: The Canadian Scleroderma Research Group is a multicenter
      SSc database that collects data annually. Using indicators of GE involvement and
      annual PFT, comparisons were made between no/mild ILD, stable moderate/severe
      ILD, and progressive moderate/severe ILD groups based on changes of FVC.
      Multivariate analyses determined associations between GE factors and ILD
      development and progression. RESULTS: There were 1043 patients with SSc (mean age
      55.7 yrs, mean disease duration 10.8 yrs); one-quarter had pulmonary fibrosis on
      chest radiograph that was related to FVC percentage predicted (Spearman's rho 
      0.39; p < 0.01). Physician indicators such as esophageal dysmotility (p = 0.009)
      and postesophageal dilatation (p = 0.041), and patient indicators such as
      difficulty swallowing (p = 0.016) and waking up choking (p = 0.026) were
      associated with low FVC. In comparing progressive and stable moderate/severe FVC
      (< 70% predicted), early satiety (p = 0.018) and a combination term of
      postdilatation and choking (p = 0.042) increased risk of progression of ILD.
      Topoisomerase I was not associated with progression over followup. CONCLUSION:
      Symptoms of esophageal dysmotility were associated with worsening FVC in SSc,
      especially if both need for esophageal dilatation and choking were present.

PMID- 23547216
TI  - Longterm effects of rituximab on B cell counts and autoantibody production in
      rheumatoid arthritis: use of high-sensitivity flow cytometry for more sensitive
      assessment of B cell depletion.
AB  - OBJECTIVE: To assess the efficacy and safety of longterm rituximab (RTX) therapy
      for rheumatoid arthritis (RA) and study correlations among B cell depletion,
      clinical response, and autoantibody production. METHODS: Seventy-seven patients
      with moderate or high RA activity received RTX and were re-treated every 6 months
      regardless of clinical response. All patients received at least 5 cycles. We
      assessed 28-joint Disease Activity Score (DAS28), IgM rheumatoid factor (RF), and
      anticitrullinated protein antibody (ACPA) levels at baseline, after 15 days, and
      then every 6 months for 24 months. Absolute CD19+ B lymphocyte counts were
      determined in 50 patients using high-sensitivity flow cytometry (hsFACS) by
      reading 100,000 events. RESULTS: After 6, 12, 18, and 24 months, 51.6%, 51.9%,
      73.3%, and 83.8% of patients, respectively, showed good European League Against
      Rheumatism responses. Significant and sustained decreases in IgM RF and ACPA
      levels were observed as early as 6 months and 12 months, respectively. The
      baseline mean absolute B cell number was 0.234 g/l. B cell numbers diminished
      significantly after the very first infusion by Day 15 (0.104 g/l; p = 0.007);
      they further decreased until 24 months (0.0013 g/l; p < 0.001). One RTX infusion
      resulted in incomplete depletion in 76.7% of patients. Upon RTX treatment,
      changes in CD19+ B cell numbers positively correlated with changes in DAS28 (r =
      0.963, p = 0.008) and IgM RF (r = 0.859, p = 0.028), but not with changes in ACPA
      production (r = 0.726, p = 0.102). The correlations between B cell numbers and
      DAS28 were observed in both ACPA-seropositive (r = 0.999, p < 0.0001) and ACPA
      negative patient subpopulations (r = 0.962, p = 0.009). The correlation between
      CD19+ cell numbers and IgM RF was observed only in the ACPA-positive population
      (r = 0.944, p = 0.005) but not in seronegative patients (r = 0.398, p = 0.435).
      No safety issues arose. CONCLUSION: In RA, clinical response to RTX is associated
      with the extent of B cell depletion and with autoantibody production. Changes in
      CD19+ B cell numbers correlate with those in disease activity and, in
      seropositive patients, also with IgM RF, but not with ACPA production. We found
      that hsFACS may be a useful method to more accurately assess incomplete B cell
      depletion.

PMID- 23547218
TI  - Safety of rituximab in combination with other biologic disease-modifying
      antirheumatic drugs in rheumatoid arthritis: an open-label study.
AB  - OBJECTIVE: To characterize the safety of rituximab (RTX) in combination with
      biologic disease-modifying antirheumatic drugs (DMARD) in patients with
      rheumatoid arthritis (RA). METHODS: We did an open-label study of the safety and
      efficacy of RTX in adult patients with active RA and an inadequate response to >=
      1 biologic for >= 12 weeks (stable dose >= 4 weeks). RTX (2 * 500 mg) was added
      to patients' current biologic and nonbiologic DMARD treatment. After 24 weeks,
      patients with 28-joint Disease Activity Score >= 2.6 were eligible for RTX
      retreatment. The primary endpoint was the proportion of patients developing a
      serious adverse event (SAE) within 24 weeks of initiating RTX. RESULTS: Patients
      (n = 176) received RTX with 18 different biologic/DMARD combinations. Adalimumab
      alone (n = 46; 26.1%) or etanercept alone (n = 37; 21.0%) plus RTX were the most
      common combinations. Overall, 90.9% and 76.1% of patients completed 24 and 48
      weeks, respectively; 147 patients (83.5%) received a second course of RTX. Over
      24 weeks, 9.1% of patients reported SAE (24.3 events/100 patient-yrs, 95% CI 15.5
      38.1). The SAE rate was similar over 48 weeks (22.4 events/100 patient-yrs, 95%
      CI 15.9-31.5). Four serious infections were reported over 48 weeks (2.7
      events/100 patient-yrs, 95% CI 1.0-7.2). No SAE occurred within 24 h of any RTX
      infusion. Efficacy responses improved numerically at Week 48 compared with Week
      24. CONCLUSION: The overall safety profile of RTX in combination with 1 other
      biologic was consistent with that previously reported for RTX plus methotrexate
      or other nonbiologic DMARD. (Clinicaltrials.gov NCT00443651).

PMID- 23547219
TI  - HLA-B27 predicts a more chronic disease course in an 8-year followup cohort of
      patients with juvenile idiopathic arthritis.
AB  - OBJECTIVE: We investigated associations of HLA-B27 with clinical manifestations
      and longterm outcome in a near population-based setting among patients with
      juvenile idiopathic arthritis (JIA). METHODS: We studied clinical and serological
      data from 410 patients with HLA-B27 results among 440 prospectively collected
      patients with JIA with 8-year followup data in a Nordic database. The study was
      structured to be as close to a population-based study as possible. RESULTS: HLA
      B27 was analyzed in 93% of patients, and was positive in 21% of the cohort, in
      18.4% of the girls and in 25.9% of the boys. Boys who were HLA-B27-positive had
      significantly higher age at onset compared to HLA-B27-negative boys and compared
      to both HLA-B27-negative and positive girls. This difference in onset age in
      relation to HLA-B27 was not found in girls. HLA-B27 was associated with clinical
      signs of sacroiliitis, enthesitis, and tenosynovitis in boys, but not in girls.
      After 8 years of disease, 46 children (11.2%) were classified as having
      enthesitis-related arthritis (ERA). Boys with ERA had clinical signs of
      sacroiliitis more often than girls with ERA. HLA-B27-positive children, as well
      as children with clinical signs of sacroiliitis, enthesitis, and hip arthritis,
      had higher odds of not being in remission off medication after 8 years of
      disease. CONCLUSION: In this near population-based Nordic JIA cohort we found
      significant differences between HLA-B27-positive boys and girls in age at disease
      onset, clinical signs of sacroiliitis, and ERA classification. HLA-B27 was
      negatively associated with longterm remission status, possibly because of its
      association with clinical disease characteristics, such as sacroiliitis, rather
      than being a general marker of persistent disease.

PMID- 23547220
TI  - Pathogen-specific risk of reactive arthritis from bacterial causes of foodborne
      illness.
AB  - OBJECTIVE: Reactive arthritis (ReA) is a sequelae of common bacterial infections
      of acute gastroenteritis. We assessed incidence of ReA following Campylobacter,
      Salmonella, Shigella, or Yersinia infection utilizing a U.S. Department of
      Defense medical database. METHODS: Subjects with acute gastroenteritis attributed
      to these pathogens were matched with >= 4 unexposed subjects. Medical history was
      analyzed for 6 months postinfection to assess for incident ReA. RESULTS: A total
      of 1753 cases of gastroenteritis were identified. ReA incidence ranged from 0 to
      4 per 100,000 person-years. CONCLUSION: These data are consistent with prior
      studies and highlight the need for continued primary prevention efforts.

PMID- 23547217
TI  - urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated
      vasculitis.
AB  - OBJECTIVE: Glomerulonephritis (GN) is common in antineutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of
      renal involvement are imperfect. We investigated 4 urinary proteins as markers of
      active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM
      1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase
      associated lipocalin (NGAL). METHODS: Patients with active renal AAV (n = 20),
      active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were
      identified within a longitudinal cohort. Urinary biomarker concentrations (by
      ELISA) were normalized for urine creatinine. Marker levels during active AAV were
      compared to baseline remission levels (from 1-4 visits) for each patient. Areas
      under receiver-operating characteristic curves (AUC), sensitivities,
      specificities, and likelihood ratios (LR) comparing disease states were
      calculated. RESULTS: Baseline biomarker levels varied among patients. All 4
      markers increased during renal flares (p < 0.05). MCP-1 discriminated best
      between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94%
      sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR
      8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently
      nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to
      distinguish active renal disease from remission (AUC 0.71-0.75). Hematuria was
      noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of
      remission samples. CONCLUSION: Either urinary MCP-1 is not specific for GN in
      AAV, or it identifies early GN not detected by standard assessment and thus has
      potential to improve care. A followup study with kidney biopsy as the gold
      standard is needed.

PMID- 23547222
TI  - Some existence results on nonlinear fractional differential equations.
AB  - In this paper, by using fixed-point methods, we study the existence and
      uniqueness of a solution for the nonlinear fractional differential equation
      boundary-value problem D(alpha)u(t)=f(t,u(t)) with a Riemann-Liouville fractional
      derivative via the different boundary-value problems u(0)=u(T), and the three
      point boundary condition u(0)=beta(1)u(eta) and u(T)=beta(2)u(eta), where T>0,
      t?I=[0,T], 0<alpha<1, 0<eta<T, 0<beta(1)<beta(2)<1.

PMID- 23547221
TI  - Statin use in giant cell arteritis: a retrospective study.
AB  - OBJECTIVE: (1) To examine the association between statin use and giant cell
      arteritis (GCA); (2) to compare the clinical features and disease course of GCA
      among statin users and nonusers. METHODS: For this retrospective study, we
      reviewed the medical records of all patients with biopsy-positive GCA diagnosed
      between 1998 and 2008. Using a case-control design, we compared the frequency of
      statin use in GCA patients to non-GCA population-based subjects who were randomly
      selected and individually matched by sex, age, and calendar year to the GCA
      cases. Statin use at diagnosis or index date and during followup was abstracted.
      In subjects with GCA, clinical information at diagnosis and followup was
      collected. RESULTS: We included 594 patients, 297 with GCA (73% female), mean age
      at diagnosis 75 years. The rate of statin exposure at index date was 18.1% for
      GCA patients versus 33.3% for controls (p < 0.001). Patients using statins were
      less likely to develop GCA compared with patients not using statins (OR 0.31, 95%
      CI 0.15-0.6, p < 0.001), even after adjustment for cardiovascular risk factors.
      Among patients with GCA, the presenting clinical features and acute-phase
      reactants were similar in patients receiving statins compared to those not on
      statin therapy. These 2 groups were also similar with regard to relapse rate,
      prednisone tapering, and overall survival. CONCLUSION: Patients using statins may
      be less likely to develop GCA compared to patients who are not using statins.
      Statin use does not appear to modify the clinical presentation or the course of
      the disease.

PMID- 23547223
TI  - On reflection symmetry and its application to the Euler-Lagrange equations in
      fractional mechanics.
AB  - We study the properties of fractional differentiation with respect to the
      reflection symmetry in a finite interval. The representation and integration
      formulae are derived for symmetric and anti-symmetric fractional derivatives,
      both of the Riemann-Liouville and Caputo type. The action dependent on the left
      sided Caputo derivatives of orders in the range (1,2) is considered and we derive
      the Euler-Lagrange equations for the symmetric and anti-symmetric part of the
      trajectory. The procedure is illustrated with an example of the action dependent
      linearly on fractional velocities. For the obtained Euler-Lagrange system, we
      discuss its localization resulting from the subsequent symmetrization of the
      action.

PMID- 23547224
TI  - Modelling heat transfer in heterogeneous media using fractional calculus.
AB  - This paper presents the results of modelling the heat transfer process in
      heterogeneous media with the assumption that part of the heat flux is dispersed
      in the air around the beam. The heat transfer process in a solid material (beam)
      can be described by an integer order partial differential equation. However, in
      heterogeneous media, it can be described by a sub- or hyperdiffusion equation
      which results in a fractional order partial differential equation. Taking into
      consideration that part of the heat flux is dispersed into the neighbouring
      environment we additionally modify the main relation between heat flux and the
      temperature, and we obtain in this case the heat transfer equation in a new form.
      This leads to the transfer function that describes the dependency between the
      heat flux at the beginning of the beam and the temperature at a given distance.
      This article also presents the experimental results of modelling real plant in
      the frequency domain based on the obtained transfer function.

PMID- 23547225
TI  - Fractional-order variational optical flow model for motion estimation.
AB  - A new class of fractional-order variational optical flow models, which
      generalizes the differential of optical flow from integer order to fractional
      order, is proposed for motion estimation in this paper. The corresponding Euler
      Lagrange equations are derived by solving a typical fractional variational
      problem, and the numerical implementation based on the Grunwald-Letnikov
      fractional derivative definition is proposed to solve these complicated
      fractional partial differential equations. Theoretical analysis reveals that the
      proposed fractional-order variational optical flow model is the generalization of
      the typical Horn and Schunck (first-order) variational optical flow model and the
      second-order variational optical flow model, which provides a new idea for us to
      study the optical flow model and has an important theoretical implication in
      optical flow model research. The experiments demonstrate the validity of the
      generalization of differential order.

PMID- 23547226
TI  - CRONE control system design toolbox for the control engineering community:
      tutorial and case study.
AB  - Fractional-order differentiation offers new degrees of freedom that simplify the
      design of high-performance dynamic controllers. The CRONE control system design
      (CSD) methodology proposes the design of robust controllers by using fractional
      order operators. A software toolbox has been developed based on this methodology
      and is freely available for the international scientific and industrial
      communities. This paper presents both the CRONE CSD methodology and its
      implementation using the toolbox. The design of two robust controllers for
      irrigation canals shows how to use the toolbox.

PMID- 23547227
TI  - Stability and convergence of an implicit numerical method for the space and time
      fractional Bloch-Torrey equation.
AB  - Fractional-order dynamics in physics, particularly when applied to diffusion,
      leads to an extension of the concept of Brownian motion through a generalization
      of the Gaussian probability function to what is termed anomalous diffusion. As
      magnetic resonance imaging is applied with increasing temporal and spatial
      resolution, the spin dynamics is being examined more closely; such examinations
      extend our knowledge of biological materials through a detailed analysis of
      relaxation time distribution and water diffusion heterogeneity. Here, the dynamic
      models become more complex as they attempt to correlate new data with a
      multiplicity of tissue compartments, where processes are often anisotropic.
      Anomalous diffusion in the human brain using fractional-order calculus has been
      investigated. Recently, a new diffusion model was proposed by solving the Bloch
      Torrey equation using fractional-order calculus with respect to time and space.
      However, effective numerical methods and supporting error analyses for the
      fractional Bloch-Torrey equation are still limited. In this paper, the space and
      time fractional Bloch-Torrey equation (ST-FBTE) in both fractional Laplacian and
      Riesz derivative form is considered. The time and space derivatives in the ST
      FBTE are replaced by the Caputo and the sequential Riesz fractional derivatives,
      respectively. Firstly, we derive an analytical solution for the ST-FBTE in
      fractional Laplacian form with initial and boundary conditions on a finite
      domain. Secondly, we propose an implicit numerical method (INM) for the ST-FBTE
      based on the Riesz form, and the stability and convergence of the INM are
      investigated. We prove that the INM for the ST-FBTE is unconditionally stable and
      convergent. Finally, we present some numerical results that support our
      theoretical analysis.

PMID- 23547228
TI  - Application of the principal fractional meta-trigonometric functions for the
      solution of linear commensurate-order time-invariant fractional differential
      equations.
AB  - A new and simplified method for the solution of linear constant coefficient
      fractional differential equations of any commensurate order is presented. The
      solutions are based on the R-function and on specialized Laplace transform pairs
      derived from the principal fractional meta-trigonometric functions. The new
      method simplifies the solution of such fractional differential equations and
      presents the solutions in the form of real functions as opposed to fractional
      complex exponential functions, and thus is directly applicable to real-world
      physics.

PMID- 23547229
TI  - A high-speed algorithm for computation of fractional differentiation and
      fractional integration.
AB  - A high-speed algorithm for computing fractional differentiations and fractional
      integrations in fractional differential equations is proposed. In this algorithm,
      the stored data are not the function to be differentiated or integrated but the
      weighted integrals of the function. The intervals of integration for the memory
      can be increased without loss of accuracy as the computing time-step n increases.
      The computing cost varies as n log n, as opposed to n(2) of standard algorithms.

PMID- 23547230
TI  - Matrix approach to discrete fractional calculus III: non-equidistant grids,
      variable step length and distributed orders.
AB  - In this paper, we further develop Podlubny's matrix approach to discretization of
      integrals and derivatives of non-integer order. Numerical integration and
      differentiation on non-equidistant grids is introduced and illustrated by several
      examples of numerical solution of differential equations with fractional
      derivatives of constant orders and with distributed-order derivatives. In this
      paper, for the first time, we present a variable-step-length approach that we
      call 'the method of large steps', because it is applied in combination with the
      matrix approach for each 'large step'. This new method is also illustrated by an
      easy-to-follow example. The presented approach allows fractional-order and
      distributed-order differentiation and integration of non-uniformly sampled
      signals, and opens the way to development of variable- and adaptive-step-length
      techniques for fractional- and distributed-order differential equations.

PMID- 23547231
TI  - Two-particle anomalous diffusion: probability density functions and self-similar
      stochastic processes.
AB  - Two-particle dispersion is investigated in the context of anomalous diffusion.
      Two different modelling approaches related to time subordination are considered
      and unified in the framework of self-similar stochastic processes. By assuming a
      single-particle fractional Brownian motion and that the two-particle correlation
      function decreases in time with a power law, the particle relative separation
      density is computed for the cases with time sub-ordination directed by a
      unilateral M-Wright density and by an extremal Levy stable density. Looking for
      advisable mathematical properties (for instance, the stationarity of the
      increments), the corresponding self-similar stochastic processes are represented
      in terms of fractional Brownian motions with stochastic variance, whose profile
      is modelled by using the M-Wright density or the Levy stable density.

PMID- 23547232
TI  - Chaos synchronization in fractional differential systems.
AB  - This paper presents a brief overview of recent developments in chaos
      synchronization in coupled fractional differential systems, where the original
      viewpoints are retained. In addition to complete synchronization, several other
      extended concepts of synchronization, such as projective synchronization, hybrid
      projective synchronization, function projective synchronization, generalized
      synchronization and generalized projective synchronization in fractional
      differential systems, are reviewed.

PMID- 23547233
TI  - Equivalent system for a multiple-rational-order fractional differential system.
AB  - The equivalent system for a multiple-rational-order (MRO) fractional differential
      system is studied, where the fractional derivative is in the sense of Caputo or
      Riemann-Liouville. With the relationship between the Caputo derivative and the
      generalized fractional derivative, we can change the MRO fractional differential
      system with a Caputo derivative into a higher-dimensional system with the same
      Caputo derivative order lying in (0,1). The stability of the zero solution to the
      original system is studied through the analysis of its equivalent system. For the
      Riemann-Liouville case, we transform the MRO fractional differential system into
      a new one with the same order lying in (0,1), where the properties of the Riemann
      Liouville derivative operator and the fractional integral operator are used. The
      corresponding stability is also studied. Finally, several numerical examples are
      provided to illustrate the derived results.

PMID- 23547234
TI  - A semi-discrete finite element method for a class of time-fractional diffusion
      equations.
AB  - As fractional diffusion equations can describe the early breakthrough and the
      heavy-tail decay features observed in anomalous transport of contaminants in
      groundwater and porous soil, they have been commonly used in the related
      mathematical descriptions. These models usually involve long-time-range
      computation, which is a critical obstacle for their application; improvement of
      computational efficiency is of great significance. In this paper, a semi-discrete
      method is presented for solving a class of time-fractional diffusion equations
      that overcome the critical long-time-range computation problem. In the procedure,
      the spatial domain is discretized by the finite element method, which reduces the
      fractional diffusion equations to approximate fractional relaxation equations. As
      analytical solutions exist for the latter equations, the burden arising from long
      time-range computation can effectively be minimized. To illustrate its efficiency
      and simplicity, four examples are presented. In addition, the method is used to
      solve the time-fractional advection-diffusion equation characterizing the bromide
      transport process in a fractured granite aquifer. The prediction closely agrees
      with the experimental data, and the heavy-tail decay of the anomalous transport
      process is well represented.

PMID- 23547235
TI  - Fractional calculus and its applications.

PMID- 23547237
TI  - Unexpected cardiac hypertrophy by epidermal growth factor receptor silencing.

PMID- 23547236
TI  - Proximal tubule angiotensin AT2 receptors mediate an anti-inflammatory response
      via interleukin-10: role in renoprotection in obese rats.
AB  - The angiotensin type 2 receptor (AT2R) has been shown to lower inflammation in
      the kidney. However, the role of the anti-inflammatory cytokine interleukin (IL)
      10 in AT2R-mediated attenuation of inflammation has not been elucidated. We
      hypothesized that AT2R activation is renoprotective by directly increasing the
      levels of anti-inflammatory cytokine IL-10 in the kidney via nitric oxide (NO)
      signaling. For in vitro studies, the human proximal tubule epithelial cell-line
      (human kidney-2 [HK-2]) was activated with lipopolysaccharide (10 MUg/mL) and
      AT2R agonist C21 (1 MUmol/L) for 24 hours, and media cytokine levels were
      assessed. Lipopolysaccharide modestly downregulated AT2R expression. Treatment
      with C21 lowered lipopolysaccharide-induced levels of both tumor necrosis factor
      alpha and IL-6, but increased IL-10 levels. Treatment with neutralizing IL-10
      antibody (1 MUg/mL) or NO synthase inhibitor L-NAME (1 mmol/L) abolished this
      effect. For in vivo studies, prehypertensive obese Zucker rats and age-matched
      lean Zucker rats were treated for 2 weeks with C21 (300 MUg/kg per day, IP) and
      AT2R antagonist (PD123319; 50 MUg/kg per minute, SC infusion). Compared with lean
      Zucker rats, obese Zucker rats had higher levels of renal AT2R expression, tumor
      necrosis factor-alpha, and IL-6. C21 treatment decreased levels of tumor necrosis
      factor-alpha by 75% and IL-6 by 60%. Conversely, PD treatment lowered the renal
      IL-10 levels in obese Zucker rats by ~60%. Renal morphometry revealed increased
      mesangial matrix expansion and glomerular macrophage infiltration, which was
      improved by C21 treatment in obese Zucker rats. Our findings suggest that
      proximal tubule AT2R activation is anti-inflammatory by increasing IL-10
      production, which is largely NO dependent and thus offers renoprotection by
      preventing early inflammation-induced renal injury in obesity.

PMID- 23547238
TI  - Chronic knockdown of the nucleus of the solitary tract AT1 receptors increases
      blood inflammatory-endothelial progenitor cell ratio and exacerbates hypertension
      in the spontaneously hypertensive rat.
AB  - AT1 receptor subtype a (AT1Ra) expression is increased in the nucleus of the
      solitary tract (NTS) in spontaneously hypertensive rat (SHR) compared with Wistar
      Kyoto controls. However, the chronic role of AT1Ra in the NTS for cardiovascular
      control is not well understood. In this study, we investigated the hypothesis
      that the NTS AT1Ra is involved in the neural regulation of the peripheral
      inflammatory status and linked with hypertension. Transduction of brain neuronal
      cultures with recombinant adeno-associated virus type 2 (AAV2)-AT1R-small hairpin
      RNA (shRNA) resulted in a 72% decrease in AT1Ra mRNA and attenuated angiotensin
      II-induced increase in extracellular signal-regulated kinase 1/2 phosphorylation
      and neuronal firing. Specific NTS microinjection of AAV2-AT1R-shRNA vector in the
      SHR resulted in a ~30 mm Hg increase in the mean arterial pressure compared with
      control vector-injected animals (Sc-shRNA: 154+/-4 mm Hg; AT1R-shRNA: 183+/-10 mm
      Hg) and induced a resetting of the baroreflex control of heart rate to higher
      mean arterial pressure. In addition, AAV2-AT1R-shRNA-treated SHRs exhibited a 74%
      decrease in circulating endothelial progenitor cells (CD90+, CD4- / CD5- / CD8-)
      and a 300% increase in the circulating inflammatory cells, including CD4+ + CD8+,
      CD45+ / 3+ T lymphocytes, and macrophages (CD68+). As a result, the endothelial
      progenitor cell/inflammatory cells ratio was decreased by 8- to 15-fold in the
      AT1R-shRNA-treated SHR. However, identical injection of AAV2-AT1R-shRNA into the
      NTS of Wistar Kyoto rats had no effect on mean arterial pressure and inflammatory
      cells. These observations suggest that increased expression of the AT1Ra in SHR
      NTS may present a counterhypertensive mechanism involving inflammatory/angiogenic
      cells.

PMID- 23547239
TI  - Integrated proteomics pipeline yields novel biomarkers for predicting
      preeclampsia.
AB  - Preeclampsia, a hypertensive pregnancy complication, is largely unpredictable in
      healthy nulliparous pregnant women. Accurate preeclampsia prediction in this
      population would transform antenatal care. To identify novel protein markers
      relevant to the prediction of preeclampsia, a 3-step mass spectrometric work flow
      was applied. On selection of candidate biomarkers, mostly from an unbiased
      discovery experiment (19 women), targeted quantitation was used to verify and
      validate candidate biomarkers in 2 independent cohorts from the SCOPE (SCreening
      fOr Pregnancy Endpoints) study. Candidate proteins were measured in plasma
      specimens collected at 19 to 21 weeks' gestation from 100 women who later
      developed preeclampsia and 200 women without preeclampsia recruited from
      Australia and New Zealand. Protein levels (n=25), age, and blood pressure were
      then analyzed using logistic regression to identify multimarker models (maximum 6
      markers) that met predefined criteria: sensitivity >=50% at 20% positive
      predictive value. These 44 algorithms were then tested in an independent European
      cohort (n=300) yielding 8 validated models. These 8 models detected 50% to 56% of
      preeclampsia cases in the training and validation sets; the detection rate for
      preterm preeclampsia cases was 80%. Validated models combine insulin-like growth
      factor acid labile subunit and soluble endoglin, supplemented with maximally 4
      markers of placental growth factor, serine peptidase inhibitor Kunitz type 1,
      melanoma cell adhesion molecule, selenoprotein P, and blood pressure. Predictive
      performances were maintained when exchanging mass spectrometry measurements with
      ELISA measurements for insulin-like growth factor acid labile subunit. In
      conclusion, we demonstrated that biomarker combinations centered on insulin-like
      growth factor acid labile subunit have the potential to predict preeclampsia in
      healthy nulliparous women.

PMID- 23547241
TI  - Determinants of the return to hometowns after the accident at Fukushima Dai-ichi
      nuclear power plant: a case study for the village of Kawauchi.
AB  - The Great East Japan Earthquake in March 2011 destroyed the Fukushima Dai-ichi
      Nuclear Power Plant (FNPP) and almost all residents in a 20 km radius from the
      plant eventually evacuated. FNPP reactors were stabilised in December 2011; some
      evacuees decided to return to their hometowns, and the other evacuees remained.
      Efforts were made to identify the determinants that affect the decision to return
      home in order to promote recovery of the surrounding area of FNPP. Seventy-one
      residents who had not returned to hometown and 56 residents who had returned were
      selected. Logistic regression analysis adjusted for confounding factors showed
      that being female [odds ratio (OR): 2.43, p = 0.03], living in areas with
      relatively higher ambient doses (OR: 3.60, p=0.01) and expressing anxiety over
      radiation exposure (OR: 8.91, p < 0.01) were independently associated with
      decisions not to return. Results of this study suggest the importance of active
      participation by scientists and local authorities in communicating the risk to
      the general population involved in returning home. 

PMID- 23547240
TI  - Differential effects of nebivolol versus metoprolol on functional sympatholysis
      in hypertensive humans.
AB  - In young healthy humans, sympathetic vasoconstriction is markedly blunted during
      exercise to optimize blood flow to the metabolically active muscle. This
      phenomenon known as functional sympatholysis is impaired in hypertensive humans
      and rats by angiotensin II-dependent mechanisms, involving oxidative stress and
      inactivation of nitric oxide (NO). Nebivolol is a beta1-adrenergic receptor
      blocker that has NO-dependent vasodilatory and antioxidant properties. We
      therefore asked whether nebivolol would restore functional sympatholysis in
      hypertensive humans. In 21 subjects with stage 1 hypertension, we measured muscle
      oxygenation and forearm blood flow responses to reflex increases in sympathetic
      nerve activity evoked by lower body negative pressure at rest, and during
      rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5-20 mg/d)
      or metoprolol (100-300 mg/d), using a double-blind crossover design. We found
      that nebivolol had no effect on lower body negative pressure-induced decreases in
      oxygenation and forearm blood flow in resting forearm (from -29+/-5% to -30+/-5%
      and from -29+/-3% to -29+/-3%, respectively; P=NS). However, nebivolol attenuated
      the lower body negative pressure-induced reduction in oxygenation and forearm
      blood flow in exercising forearm (from -14+/-4% to -1+/-5% and from -15+/-2% to 
      6+/-2%, respectively; both P<0.05). This effect of nebivolol on oxygenation and
      forearm blood flow in exercising forearm was not observed with metoprolol in the
      same subjects, despite a similar reduction in blood pressure. Nebivolol had no
      effect on sympathetic nerve activity at rest or during handgrip, suggesting a
      direct effect on vascular function. Thus, our data demonstrate that nebivolol
      restored functional sympatholysis in hypertensive humans by a mechanism that does
      not involve beta1-adrenergic receptors. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01502787.

PMID- 23547242
TI  - Pervasive competition between threat and reward in the brain.
AB  - In the current functional MRI study, we investigated interactions between reward
      and threat processing. Visual cues at the start of each trial informed
      participants about the chance of winning monetary reward and/or receiving a mild
      aversive shock. We tested two competing hypothesis: according to the 'salience
      hypothesis', in the condition involving both reward and threat, enhanced
      activation would be observed because of increased salience; according to the
      'competition hypothesis', the processing of reward and threat would trade-off
      against each other, leading to reduced activation. Analysis of skin conductance
      data during a delay phase revealed an interaction between reward and threat
      processing, such that the effect of reward was reduced during threat and the
      effect of threat was reduced during reward. Analysis of imaging data during the
      same task phase revealed interactions between reward and threat processing in
      several regions, including the midbrain/ventral tegmental area, caudate, putamen,
      bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus and
      dorsal anterior cingulate cortex. Taken together, our findings reveal conditions
      during which reward and threat trade-off against each other across multiple
      sites. Such interactions are suggestive of competitive processes and may reflect
      the organization of opponent systems in the brain.

PMID- 23547243
TI  - Differential patterns of nucleus accumbens activation during anticipation of
      monetary and social reward in young and older adults.
AB  - Recent studies have reported inconsistent results regarding the loss of reward
      sensitivity in the aging brain. Although such an age effect might be due to a
      decline of physiological processes, it may also be a consequence of age-related
      changes in motivational preference for different rewards. Here, we examined
      whether the age effects on neural correlates of reward anticipation are modulated
      by the type of expected reward. Functional magnetic resonance images were
      acquired in 24 older (60-78 years) and 24 young participants (20-28 years) while
      they performed an incentive delay task offering monetary or social rewards.
      Anticipation of either reward type recruited brain structures associated with
      reward, including the nucleus accumbens (NAcc). Region of interest analysis
      revealed an interaction effect of reward type and age group in the right NAcc:
      enhanced activation to cues of social reward was detected in the older subsample
      while enhanced activation to cues of monetary reward was detected in the younger
      subsample. Our results suggest that neural sensitivity to reward-predicting cues
      does not generally decrease with age. Rather, neural responses in the NAcc appear
      to be modulated by the type of reward, presumably reflecting age-related changes
      in motivational value attributed to different types of reward.

PMID- 23547244
TI  - Timing the fearful brain: unspecific hypervigilance and spatial attention in
      early visual perception.
AB  - Numerous studies suggest that anxious individuals are more hypervigilant to
      threat in their environment than nonanxious individuals. In the present event
      related potential (ERP) study, we sought to investigate the extent to which
      afferent cortical processes, as indexed by the earliest visual component C1, are
      biased in observers high in fear of specific objects. In a visual search
      paradigm, ERPs were measured while spider-fearful participants and controls
      searched for discrepant objects (e.g., spiders, butterflies, flowers) in visual
      arrays. Results showed enhanced C1 amplitudes in response to spatially directed
      target stimuli in spider-fearful participants only. Furthermore, enhanced C1
      amplitudes were observed in response to all discrepant targets and distractors in
      spider-fearful compared with non-anxious participants, irrespective of fearful
      and non-fearful target contents. This pattern of results is in line with
      theoretical notions of heightened sensory sensitivity (hypervigilance) to
      external stimuli in high-fearful individuals. Specifically, the findings suggest
      that fear facilitates afferent cortical processing in the human visual cortex in
      a non-specific and temporally sustained fashion, when observers search for
      potential threat cues.

PMID- 23547245
TI  - Experimental human endotoxemia enhances brain activity during social cognition.
AB  - Acute peripheral inflammation with corresponding increases in peripheral
      cytokines affects neuropsychological functions and induces depression-like
      symptoms. However, possible effects of increased immune responses on social
      cognition remain unknown. Therefore, this study investigated the effects of
      experimentally induced acute inflammation on performance and neural responses
      during a social cognition task assessing Theory of Mind (ToM) ability. In this
      double-blind randomized crossover functional magnetic resonance imaging study, 18
      healthy right-handed male volunteers received an injection of bacterial
      lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro
      and anti-inflammatory cytokines as well as mood ratings were analyzed together
      with brain activation during a validated ToM task (i.e. Reading the Mind in the
      Eyes Test). LPS administration induced pronounced transient increases in pro- (IL
      6, TNF-alpha) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as
      decreases in mood. Social cognition performance was not affected by acute
      inflammation. However, altered neural activity was observed during the ToM task
      after LPS administration, reflected by increased responses in the fusiform gyrus,
      temporo-parietal junction, superior temporal gyrus and precuneus. The increased
      task-related neural responses in the LPS condition may reflect a compensatory
      strategy or a greater social cognitive processing as a function of sickness.

PMID- 23547246
TI  - A neural signature of the creation of social evaluation.
AB  - Previous research has shown that receiving an unfair monetary offer in economic
      bargaining elicits also-called feedback negativity (FN). This scalp-recorded
      brain potential probably reflects a bad-vs-good evaluation in the medial frontal
      cortex and has been linked to fundamental processes of reinforcement learning. In
      the present study, we investigated whether the evaluative mechanism indexed by
      the FN is also involved in learning who is an unfair vs fair bargaining partner.
      An electroencephalogram was recorded while participants completed a computerized
      version of the Ultimatum Game, repeatedly receiving fair or unfair monetary
      offers from alleged other participants. Some of these proposers were either
      always fair or always unfair in their offers. In each trial, participants first
      saw a portrait picture of the respective proposer before the monetary offer was
      presented. Therefore, the faces could be used as predictive cues for the fairness
      of the pending offers. We found that not only unfair offers themselves induced a
      FN, but also (over the task) faces of unfair proposers. Thus, when interaction
      partners repeatedly behave in an unfair way, their faces acquire a negative
      valence, which manifests in a basal neural mechanism of bad-vs-good evaluation.

PMID- 23547248
TI  - Andalusian initiative for advanced therapies: fostering synergies.

PMID- 23547247
TI  - Variation in oxytocin receptor gene (OXTR) polymorphisms is associated with
      emotional and behavioral reactions to betrayal.
AB  - Variations in the gene that encodes the oxytocin receptor (OXTR) have been
      associated with many aspects of social cognition as well as several prosocial
      behaviors. However, potential associations of OXTR variants with reactions to
      betrayals of trust while cooperating for mutual benefit have not yet been
      explored. We examined how variations in 10 single-nucleotide polymorphisms on
      OXTR were associated with behavior and emotional reactions after a betrayal of
      trust in an iterated Prisoner's Dilemma Game. After correction for multiple
      testing, one haplotype (C-rs9840864, T-rs2268494) was significantly associated
      with faster retaliation post-betrayal-an association that appeared to be due to
      this haplotype's intermediate effect of exacerbating people's anger after they
      had been betrayed. Furthermore, a second haplotype (A-rs237887, C-rs2268490) was
      associated with higher levels of post-betrayal satisfaction, and a third
      haplotype (G-rs237887, C-rs2268490) was associated with lower levels of post
      betrayal satisfaction.

PMID- 23547250
TI  - A farewell and a welcome.

PMID- 23547249
TI  - Dynamic diagnosis of "fishmouthing" syndrome, an overlooked complication of
      blepharoplasty.
AB  - BACKGROUND: Dysfunction and/or dehiscence of the lateral canthus is 1 source of
      symptomatic eyelid closure disorder after blepharoplasty. Because the resulting
      concentric blinking movement resembles mouth closure in a fish, the name
      "fishmouthing" syndrome (FS) was given to this condition. Fishmouthing syndrome
      appears to be an overlooked complication of blepharoplasty. OBJECTIVES: The
      authors performed dynamic assessments of patients who had eyelid discomfort after
      blepharoplasty to establish the clinical signs of FS. METHODS: Preoperative and
      postoperative videos of 36 patients who presented for secondary blepharoplasty
      were analyzed retrospectively. All 36 patients experienced symptoms of dry eyes
      and eye discomfort after their initial blepharoplasty and desired symptomatic and
      cosmetic improvement. The dynamic signs and diagnostic criteria for FS were
      established clinically and through video analysis of patients' blinking
      movements. RESULTS: The most common clinical characteristics of FS included lash
      deformity ("cow lash" sign), abnormal medial displacement of the lateral canthus
      during blinking, deformity (rounding/narrowing) of the lateral scleral triangle,
      and visible eyelid closure deficiency or gapping. Other characteristics were
      lower-lid retraction and compensatory hypercontraction of the orbicularis oculi
      adjacent to the inner canthus. CONCLUSIONS: Patients with FS present with a
      combination of clinical symptoms and signs and are best diagnosed through dynamic
      visualization of the animated tissue during blinking. Evaluation of preoperative
      videos is an essential tool for surgical planning and for analyzing the results,
      both before and after corrective surgery, in patients with potential FS. LEVEL OF
      EVIDENCE: 4.

PMID- 23547251
TI  - In memoriam - Hugh A. Smythe, 1927-2012.

PMID- 23547252
TI  - Patients with rheumatoid arthritis have more vulnerable arterial plaques, but
      lowering disease activity may stabilize this threat.

PMID- 23547253
TI  - Patient-reported remission in rheumatoid arthritis.

PMID- 23547254
TI  - Adding new perspectives to the kaleidoscope of remission criteria in rheumatoid
      arthritis.

PMID- 23547255
TI  - Criteria for gout diagnosis?

PMID- 23547256
TI  - Ochronosis of the hip joint.

PMID- 23547257
TI  - ABC transporter genes and methotrexate response in rheumatoid arthritis.

PMID- 23547259
TI  - Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway
      alters stress granule formation.
AB  - Stress granules (SG) are cytoplasmic multimeric RNA bodies that form under stress
      conditions known to inhibit cap-dependent translation. SG contain translation
      initiation factors, RNA binding proteins, and signaling molecules. SG are known
      to inhibit apoptotic pathways, thus contributing to chemo- and radioresistance in
      tumor cells. However, whether stress granule formation involves oncogenic
      signaling pathways is currently unknown. Here, we report a novel role of the
      mTORC1-eukaryotic translation initiation factor 4E (eIF4E) pathway, a key
      regulator of cap-dependent translation initiation of oncogenic factors, in SG
      formation. mTORC1 specifically drives the eIF4E-mediated formation of SG through
      the phosphorylation of 4E-BP1, a key factor known to inhibit formation of the
      mTORC1-dependent eIF4E-eIF4GI interactions. Disrupting formation of SG by
      inactivation of mTOR with its specific inhibitor pp242 or by depletion of eIF4E
      or eIF4GI blocks the SG-associated antiapoptotic p21 pathway. Finally, pp242
      sensitizes cancer cells to death in vitro and inhibits the growth of
      chemoresistant tumors in vivo. This work therefore highlights a novel role of the
      oncogenic mTORC1-eIF4E pathway, namely, the promotion of formation of
      antiapoptotic SG.

PMID- 23547260
TI  - A regulatory role for microRNA 33* in controlling lipid metabolism gene
      expression.
AB  - hsa-miR-33a and hsa-miR-33b, intronic microRNAs (miRNAs) located within the
      sterol regulatory element-binding protein 2 and 1 genes (Srebp-2 and -1),
      respectively, have recently been shown to regulate lipid homeostasis in concert
      with their host genes. Although the functional role of miR-33a and -b has been
      highly investigated, the role of their passenger strands, miR-33a* and -b*,
      remains unclear. Here, we demonstrate that miR-33a* and -b* accumulate to steady
      state levels in human, mouse, and nonhuman primate tissues and share a similar
      lipid metabolism target gene network as their sister strands. Analogous to miR
      33, miR-33* represses key enzymes involved in cholesterol efflux (ABCA1 and
      NPC1), fatty acid metabolism (CROT and CPT1a), and insulin signaling (IRS2).
      Moreover, miR-33* also targets key transcriptional regulators of lipid
      metabolism, including SRC1, SRC3, NFYC, and RIP140. Importantly, inhibition of
      either miR-33 or miR-33* rescues target gene expression in cells overexpressing
      pre-miR-33. Consistent with this, overexpression of miR-33* reduces fatty acid
      oxidation in human hepatic cells. Altogether, these data support a regulatory
      role for the miRNA* species and suggest that miR-33 regulates lipid metabolism
      through both arms of the miR-33/miR-33* duplex.

PMID- 23547261
TI  - Bmal1 and beta-cell clock are required for adaptation to circadian disruption,
      and their loss of function leads to oxidative stress-induced beta-cell failure in
      mice.
AB  - Circadian disruption has deleterious effects on metabolism. Global deletion of
      Bmal1, a core clock gene, results in beta-cell dysfunction and diabetes. However,
      it is unknown if this is due to loss of cell-autonomous function of Bmal1 in beta
      cells. To address this, we generated mice with beta-cell clock disruption by
      deleting Bmal1 in beta cells (beta-Bmal1(-/-)). beta-Bmal1(-/-) mice develop
      diabetes due to loss of glucose-stimulated insulin secretion (GSIS). This loss of
      GSIS is due to the accumulation of reactive oxygen species (ROS) and consequent
      mitochondrial uncoupling, as it is fully rescued by scavenging of the ROS or by
      inhibition of uncoupling protein 2. The expression of the master antioxidant
      regulatory factor Nrf2 (nuclear factor erythroid 2-related factor 2) and its
      targets, Sesn2, Prdx3, Gclc, and Gclm, was decreased in beta-Bmal1(-/-) islets,
      which may contribute to the observed increase in ROS accumulation. In addition,
      by chromatin immunoprecipitation experiments, we show that Nrf2 is a direct
      transcriptional target of Bmal1. Interestingly, simulation of shift work-induced
      circadian misalignment in mice recapitulates many of the defects seen in Bmal1
      deficient islets. Thus, the cell-autonomous function of Bmal1 is required for
      normal beta-cell function by mitigating oxidative stress and serves to preserve
      beta-cell function in the face of circadian misalignment.

PMID- 23547262
TI  - Ablation of dihydroceramide desaturase 1, a therapeutic target for the treatment
      of metabolic diseases, simultaneously stimulates anabolic and catabolic
      signaling.
AB  - The lipotoxicity hypothesis posits that obesity predisposes individuals to
      metabolic diseases because the oversupply of lipids to tissues not suited for fat
      storage leads to the accumulation of fat-derived molecules that impair tissue
      function. Means of combating this have been to stimulate anabolic processes to
      promote lipid storage or to promote catabolic ones to drive fat degradation.
      Herein, we demonstrate that ablating dihydroceramide desaturase 1 (Des1), an
      enzyme that produces ceramides, leads to the simultaneous activation of both
      anabolic and catabolic signaling pathways. In cells lacking Des1, the most common
      sphingolipids were replaced with dihydro forms lacking the double bond inserted
      by Des1. These cells exhibited a remarkably strong activation of the
      antiapoptotic and anabolic signaling pathway regulated by Akt/protein kinase B
      (PKB), were resistant to apoptosis, and were considerably larger than their wild
      type counterparts. Paradoxically, Des1(-/-) cells exhibited high levels of
      autophagy. Mechanistic studies revealed that this resulted from impaired ATP
      synthesis due in part to decreased expression and activity of several complexes
      of the electron transport chain, particularly complex IV, leading to activation
      of AMP-activated protein kinase and its induction of the autophagosome. Thus,
      Des1 ablation enhanced starvation responses but dissociated them from the
      anabolic, prosurvival, and antiautophagic Akt/PKB pathways.

PMID- 23547263
TI  - Squeezers and leaf-cutters: differential diversification and degeneration of the
      venom system in toxicoferan reptiles.
AB  - Although it has been established that all toxicoferan squamates share a common
      venomous ancestor, it has remained unclear whether the maxillary and mandibular
      venom glands are evolving on separate gene expression trajectories or if they
      remain under shared genetic control. We show that identical transcripts are
      simultaneously expressed not only in the mandibular and maxillary glands, but
      also in the enigmatic snake rictal gland. Toxin molecular frameworks recovered in
      this study were three-finger toxin (3FTx), CRiSP, crotamine (beta-defensin),
      cobra venom factor, cystatin, epididymal secretory protein, kunitz, L-amino acid
      oxidase, lectin, renin aspartate protease, veficolin, and vespryn. We also
      discovered a novel low-molecular weight disulfide bridged peptide class in
      pythonid snake glands. In the iguanian lizards, the most highly expressed are
      potentially antimicrobial in nature (crotamine (beta-defensin) and cystatin),
      with crotamine (beta-defensin) also the most diverse. However, a number of
      proteins characterized from anguimorph lizards and caenophidian snakes with
      hemotoxic or neurotoxic activities were recruited in the common toxicoferan
      ancestor and remain expressed, albeit in low levels, even in the iguanian
      lizards. In contrast, the henophidian snakes express 3FTx and lectin toxins as
      the dominant transcripts. Even in the constricting pythonid and boid snakes,
      where the glands are predominantly mucous-secreting, low-levels of toxin
      transcripts can be detected. Venom thus appears to play little role in feeding
      behavior of most iguanian lizards or the powerful constricting snakes, and the
      low levels of expression argue against a defensive role. However, clearly the
      incipient or secondarily atrophied venom systems of these taxa may be a source of
      novel compounds useful in drug design and discovery.

PMID- 23547264
TI  - Seven benzimidazole pesticides combined at sub-threshold levels induce
      micronuclei in vitro.
AB  - Benzimidazoles act by disrupting microtubule polymerisation and are capable of
      inducing the formation of micronuclei. Considering the similarities in their
      mechanisms of action (inhibition of microtubule assembly by binding to the
      colchicine-binding site on tubulin monomers), combination effects according to
      the principles of concentration addition might occur. If so, it is to be expected
      that several benzimidazoles contribute to micronucleus formation even when each
      single one is present at or below threshold levels. This would have profound
      implications for risk assessment, but the idea has never been tested rigorously.
      To fill this gap, we analysed micronucleus frequencies for seven benzimidazoles,
      including the fungicide benomyl, its metabolite carbendazim, the anthelmintics
      albendazole, albendazole oxide, flubendazole, mebendazole and oxibendazole.
      Thiabendazole was also tested but was inactive. We used the cytochalasin-blocked
      micronucleus assay with CHO-K1 cells according to OECD guidelines, and employed
      an automated micronucleus scoring system based on image analysis to establish
      quantitative concentration-response relationships for the seven active
      benzimidazoles. Based on this information, we predicted additive combination
      effects for a mixture of the seven benzimidazoles by using the concepts of
      concentration addition and independent action. The observed effects of the
      mixture agreed very well with those predicted by concentration addition.
      Independent action underestimated the observed combined effects by a large
      margin. With a mixture that combined all benzimidazoles at their estimated
      threshold concentrations for micronucleus induction, micronucleus frequencies of
      ~15.5% were observed, correctly anticipated by concentration addition. On the
      basis of independent action, this mixture was expected to produce no effects. Our
      data provide convincing evidence that concentration addition is applicable to
      combinations of benzimidazoles that form micronuclei by disrupting microtubule
      polymerisation. They present a rationale for grouping these chemicals together
      for the purpose of cumulative risk assessment.

PMID- 23547265
TI  - Predicting cognitive decline: a dementia risk score vs. the Framingham vascular
      risk scores.
AB  - OBJECTIVE: Our aim was to compare 2 Framingham vascular risk scores with a
      dementia risk score in relation to 10-year cognitive decline in late middle age.
      METHODS: Participants were men and women with mean age of 55.6 years at baseline,
      from the Whitehall II study, a longitudinal British cohort study. We compared the
      Framingham general cardiovascular disease risk score and the Framingham stroke
      risk score with the cardiovascular risk factors, aging and dementia (CAIDE) risk
      score that uses risk factors in midlife to estimate risk of late-life dementia.
      Cognitive tests included reasoning, memory, verbal fluency, vocabulary, and
      global cognition, assessed 3 times over 10 years. RESULTS: Higher cardiovascular
      disease risk and higher stroke risk were associated with greater cognitive
      decline in all tests except memory; higher dementia risk was associated with
      greater decline in reasoning, vocabulary, and global cognitive scores. Compared
      with the dementia risk score, cardiovascular and stroke risk scores showed
      slightly stronger associations with 10-year cognitive decline; these differences
      were statistically significant for semantic fluency and global cognitive scores.
      For example, cardiovascular disease risk was associated with -0.06 SD (95%
      confidence interval [CI] = -0.08, -0.05) decline in the global cognitive scores
      over 10 years whereas dementia risk was associated with -0.03 SD (95% CI = -0.04,
      -0.01) decline (difference in beta coefficients = 0.03; 95% CI = 0.01, 0.05).
      CONCLUSIONS: The CAIDE dementia and Framingham risk scores predict cognitive
      decline in late middle age but the Framingham risk scores may have an advantage
      over the dementia risk score for use in primary prevention for assessing risk of
      cognitive decline and targeting of modifiable risk factors.

PMID- 23547266
TI  - The first steps of clinical neurology in South America.

PMID- 23547268
TI  - Vibration-induced reversal of spontaneous nystagmus in lateral medullary
      infarction.

PMID- 23547267
TI  - Meta-analysis of amyloid-cognition relations in cognitively normal older adults.
AB  - OBJECTIVE: We conducted a meta-analysis of relationships between amyloid burden
      and cognition in cognitively normal, older adult humans. METHODS: Methods of
      assessing amyloid burden included were CSF or plasma assays, histopathology, and
      PET ligands. Cognitive domains examined were episodic memory, executive function,
      working memory, processing speed, visuospatial function, semantic memory, and
      global cognition. Sixty-four studies representing 7,140 subjects met selection
      criteria, with 3,495 subjects from 34 studies representing independent cohorts.
      Weighted effect sizes were obtained for each study. Primary analyses were
      conducted limiting to independent cohort studies using only the most common
      assessment method (Pittsburgh compound B). Exploratory analyses included all
      assessment methods. RESULTS: Episodic memory (r = 0.12) had a significant
      relationship to amyloid burden. Executive function and global cognition did not
      have significant relationships to amyloid in the primary analysis of Pittsburgh
      compound B (r = 0.05 and r = 0.08, respectively), but did when including all
      assessment methods (r = 0.08 and r = 0.09, respectively). The domains of working
      memory, processing speed, visuospatial function, and semantic memory did not have
      significant relationships to amyloid. Differences in the method of amyloid
      assessment, study design (longitudinal vs cross-sectional), or inclusion of
      control variables (age, etc.) had little influence. CONCLUSIONS: Based on this
      meta-analytic survey of the literature, increased amyloid burden has small but
      nontrivial associations with specific domains of cognitive performance in
      individuals who are currently cognitively normal. These associations may be
      useful for identifying preclinical Alzheimer disease or developing clinical
      outcome measures.

PMID- 23547269
TI  - Brain disorders where resources are scarce: the unfinished agenda.

PMID- 23547270
TI  - Sleep-disordered breathing in multiple sclerosis.

PMID- 23547271
TI  - Clinical reasoning: Psychomotor regression in the young.

PMID- 23547272
TI  - Pearls and oy-sters: the utility of cytology and flow cytometry in the diagnosis
      of leptomeningeal leukemia.
AB  - Diagnosis of leptomeningeal leukemia (and more broadly, leptomeningeal metastasis
      [LM]) is based on:

PMID- 23547273
TI  - Teaching neuroimages: anoxic brain injury with unilateral hemispheric cortical
      involvement.
AB  - A 55-year-old woman collapsed with chest pain and cardiac arrest. Her pulse was
      restored after 6 minutes of cardiopulmonary resuscitation, but she remained
      comatose. Brain MRI (figure) revealed bilateral basal ganglia and right
      hemispheric cortical lesion, which was typical for anoxic brain injury except for
      the unilateral cortical involvement. Neck CT angiography showed severe stenosis
      in the right proximal internal carotid artery. The unilateral cortical injury
      could be explained by compromised cerebral blood flow due to preexisting carotid
      stenosis. This case demonstrates an atypical pattern of anoxic brain injury
      secondary to focal vascular stenosis.

PMID- 23547274
TI  - Teaching video neuroimages: orthostatic tremor: the helicopter sign.
AB  - A 63-year-old man presented with 4 years of orthostatic tremor while standing,
      resolving after sitting or leaning against a wall. There was marked subjective
      unsteadiness, but no falls. Surface EMG in arms and legs demonstrated a 14- to 16
      Hz synchronous tremor in antagonist muscles (video on the Neurology Web site at
      www.neurology.org.).

PMID- 23547275
TI  - Effectiveness of a health professional training program for treatment of tobacco
      addiction.
AB  - INTRODUCTION: Advice can have a small but clinically important effect in
      promoting smoking cessation. Where studied, the rate of delivery has been found
      to be low. Training has been found to increases this rates, but there is little
      research on effectiveness in terms of smoking cessation rates. This study aimed
      to assess the effectiveness and cost-effectiveness of an health professionals
      educational program to increase long-term rates of nicotine abstinence in smoking
      outpatients. METHODS: We conducted a pragmatic cluster-randomized, controlled
      trial in 35 primary health care centers in Spain. Participants were all 830
      health professionals who attended 5,970 smokers during recruiting period. After
      that we measured continuous abstinence 6 months after the intervention and
      biochemically validated (saliva cotinine test) 1 year following intervention.
      Cost-effectiveness was measured in terms of cost per life year gained. RESULTS:
      After 6 months, the rate of continuous abstinence was significantly higher in the
      intervention group (2.1% vs. 0.3%, p > .0001) with an odds ratio of 6.5 (95% CI =
      3.3-12.7). After 1 year, biochemical validation was performed on 31 of the 67
      patients previously registered as abstinent. All of them were abstinent and
      belonged to intervention group. The incremental cost per life year gained after 6
      months was ?969. CONCLUSIONS: A primary care training program on smoking
      cessation based on scientific evidence, behavioral theory, and active learning
      methods increases long-term continuous nicotine abstinence rate among outpatients
      in a significant way. These may be relevant for planning training of
      professionals, clinical assistance, and public health programs.

PMID- 23547276
TI  - Weight concerns among Finnish ever-smokers: a population-based study.
AB  - INTRODUCTION: Concern over weight gain after smoking cessation has been
      hypothesized to discourage quit attempts and consequently reduce smoking
      cessation rates. The aim of this study was to examine the association between
      smoking status and weight concerns among a population-based sample of Finnish
      ever-smokers. METHODS: Data were collected in conjunction with the National
      FINRISK 2007 Study from a population-based sample of 25- to 74-yearold Finns.
      These analyses were based on a subsample of 1,614 ever-smokers. Participants were
      divided into 4 groups (daily smokers, occasional smokers, recent quitters, and
      former smokers) based on the self-reported smoking status. Weight concerns were
      analyzed as a sum score including 6 items (range 0-24). Regression analyses were
      used to examine the association between smoking status and weight concerns, while
      adjusting for multiple confounders. RESULTS: Smoking status was significantly
      associated with weight concerns, current daily smokers reporting the highest
      levels of weight concerns. After adjusting for potential confounders (age,
      gender, body mass index, socioeconomic status, and health behavior), the weight
      concerns of daily smokers remained significantly higher in comparison with all
      other groups. Although women were more concerned about their weight than men, no
      gender-specific associations were found between weight concerns and smoking
      status. CONCLUSIONS: Current daily smokers are more concerned about their weight
      than recent quitters, as well as former and occasional smokers. Weight concerns
      should be taken into account in tobacco dependence treatment.

PMID- 23547277
TI  - Lower education level is a major risk factor for peritonitis incidence in chronic
      peritoneal dialysis patients: a retrospective cohort study with 12-year follow
      up.
AB  - BACKGROUND: Peritoneal dialysis (PD)-related peritonitis remains an important
      complication in PD patients, potentially causing technique failure and
      influencing patient outcome. To date, no comprehensive study in the Taiwanese PD
      population has used a time-dependent statistical method to analyze the factors
      associated with PD-related peritonitis. METHODS: Our single-center retrospective
      cohort study, conducted in southern Taiwan between February 1999 and July 2010,
      used time-dependent statistical methods to analyze the factors associated with PD
      related peritonitis. RESULTS: The study recruited 404 PD patients for analysis,
      150 of whom experienced at least 1 episode of peritonitis during the follow-up
      period. The incidence rate of peritonitis was highest during the first 6 months
      after PD start. A comparison of patients in the two groups (peritonitis vs null
      peritonitis) by univariate analysis showed that the peritonitis group included
      fewer men (p = 0.048) and more patients of older age (>=65 years, p = 0.049). In
      addition, patients who had never received compulsory education showed a
      statistically higher incidence of PD-related peritonitis in the univariate
      analysis (p = 0.04). A proportional hazards model identified education level
      (less than elementary school vs any higher education level) as having an
      independent association with PD-related peritonitis [hazard ratio (HR): 1.45; 95%
      confidence interval (CI): 1.01 to 2.06; p = 0.045). Comorbidities measured using
      the Charlson comorbidity index (score >2 vs <=2) showed borderline statistical
      significance (HR: 1.44; 95% CI: 1.00 to 2.13; p = 0.053). CONCLUSIONS: A lower
      education level is a major risk factor for PD-related peritonitis independent of
      age, sex, hypoalbuminemia, and comorbidities. Our study emphasizes that a
      comprehensive PD education program is crucial for PD patients with a lower
      education level.

PMID- 23547278
TI  - Effects of a pre-dialysis patient education program on the relative frequencies
      of dialysis modalities.
AB  - BACKGROUND: Pre-dialysis education can guide the choice of the dialysis modality
      best tailored to meet the needs and preferences of individual patients with
      chronic kidney disease. METHODS: In a retrospective single-center cohort study,
      we evaluated the impact of a pre-dialysis education program on the incidence
      rates of patients using hemodialysis (HD) and peritoneal dialysis (PD) in our
      unit. The frequency distribution of dialysis modalities between people attending
      our education program and people not attending the program (control group) was
      analyzed for the 4-year period 2004 - 2008. RESULTS: From among all the incident
      chronic kidney disease 5D patients presenting during the 4-year period, we
      analyzed 227 who started dialysis either with an arteriovenous fistula or a PD
      catheter. In that cohort, 70 patients (30.8%) took part in the education program,
      and 157 (69.2%) did not receive structured pre-dialysis counseling. In the group
      receiving education, 38 patients (54.3%) started with PD, and 32 (45.7%), with
      HD. In the standard-care group not receiving education, 44 patients (28%) started
      with PD, and 113 (72%), with HD (p < 0.001). CONCLUSIONS: Our multidisciplinary
      pre-dialysis program had a significant impact on the frequency distribution of
      dialysis modalities, increasing the proportion of patients initiating dialysis
      with PD.

PMID- 23547282
TI  - Mixed interests. Interview by Kristie Nybo.

PMID- 23547281
TI  - 30 years of methods.

PMID- 23547279
TI  - Blood pressure measurement in peritoneal dialysis: which method is best?
AB  - BACKGROUND: The optimal approach to monitoring blood pressure (BP) in the
      peritoneal dialysis (PD) population is unclear. Ambulatory BP monitoring reliably
      predicts prognosis, but can be inconvenient. The accuracy of home BP monitoring
      in this population is unproven. The automated BpTRU device (BpTRU Medical
      Devices, Coquitlam, BC, Canada), which provides an average of up to 6 successive
      in-office BP measurements, has not been studied in this patient group. METHODS:
      We studied 17 patients (average age: 54 +/- 12 years; 12 men, 5 women; 94% on
      automated PD) attending a single center. All patients underwent office, home,
      BpTRU, and ambulatory BP measurement. The reference standard for analysis was
      daytime ambulatory BP. Correlation between the referent method and each
      comparator method was determined (Pearson correlation coefficient), and Bland
      Altman scatter plots depicting the differences in the BP measurements were
      constructed. RESULTS: Mean office BP (126.4 +/- 16.9/78.8 +/- 11.6 mmHg) and
      BpTRU BP (123.8 +/- 13.7/80.7 +/- 11.1 mmHg) closely approximated mean daytime
      ambulatory BP (129.3 +/- 14.8/78.2 +/- 7.9 mmHg). Mean home BP (143.8 +/-
      15.0/89.9 +/- 28.1 mmHg) significantly overestimated mean daytime systolic BP by
      14.2 mmHg (95% confidence interval: 4.3 mmHg to 24.1 mmHg; p = 0.008). Bland
      Altman plots demonstrated poorest agreement between home BP and daytime
      ambulatory BP. No patient had "white-coat hypertension," and only 1 patient had
      false-resistant hypertension. Most patients showed abnormal nocturnal dipping
      patterns (non-dipping: n = 11; reverse-dipping: n = 5; normal dipping: n = 1).
      CONCLUSIONS: We report a novel finding that BP measurement using the BpTRU device
      is more accurate than home BP measurement in a PD population. Potential
      explanations for this observation include poor home BP measurement technique, use
      of poorly validated home BP measurement devices, or a reduced prevalence of white
      coat effect among PD patients. Our study also confirms that, in the PD
      population, BP measurements vary considerably with patient location, time of day,
      and measurement technique.

PMID- 23547280
TI  - Comparison of direct medical costs between automated and continuous ambulatory
      peritoneal dialysis.
AB  - OBJECTIVE: We set out to estimate the direct medical costs (DMCs) of peritoneal
      dialysis (PD) and to compare the DMCs for continuous ambulatory PD (CAPD) and
      automated PD (APD). In addition, DMCs according to age, sex, and the presence of
      peritonitis were evaluated. METHODS: Our retrospective cohort analysis considered
      patients initiating PD, calculating 2008 costs and, for comparison, updating the
      results for 2010. The analysis took the perspective of the Mexican Institute of
      Social Security, including outpatient clinic and emergency room visits, dialysis
      procedures, medications, laboratory tests, hospitalizations, and surgeries.
      RESULTS: No baseline differences were observed for the 41 patients evaluated (22
      on CAPD, 19 on APD). Median annual DMCs per patient on PD were US$15 072 in 2008
      and US$16 452 in 2010. When analyzing percentage distribution, no differences
      were found in the DMCs for the modality groups. In both APD and CAPD, the main
      costs pertained to the dialysis procedure (CAPD 41%, APD 47%) and
      hospitalizations (CAPD 37%, APD 32%). Dialysis procedures cost significantly more
      (p = 0.001) in APD (US$7 084) than in CAPD (US$6 071), but total costs (APD US$15
      389 vs CAPD US$14 798) and other resources were not different. The presence of
      peritonitis increased the total costs (US$16 075 vs US$14 705 for patients
      without peritonitis, p = 0.05), but in the generalized linear model analysis,
      DMCs were not predicted by age, sex, dialysis modality, or peritonitis. A similar
      picture was observed for costs extrapolated to 2010, with a 10% - 20% increase
      for each component--except for laboratory tests, which increased 52%, and
      dialysis procedures, which decreased 3%, from 2008. CONCLUSIONS: The annual DMCs
      per patient on PD in this study were US$15 072 in 2008 and US$16 452 in 2010.
      Total DMCs for dialysis procedures were higher in APD than in CAPD, but the
      difference was not statistically significant. In both APD and CAPD, 90% of costs
      were attributable to the dialysis procedure, hospitalizations, and medications.
      In a multivariate analysis, no independent variable significantly predicted a
      higher DMC.

PMID- 23547284
TI  - Method of the Year 2012.

PMID- 23547283
TI  - qPCR: Single copy targets.

PMID- 23547285
TI  - The author file: John Yates III.

PMID- 23547286
TI  - Stem cells: Blood matters.

PMID- 23547287
TI  - Molecular engineering: Changing the channel.

PMID- 23547288
TI  - Epigenetics: Reading methylated genomes.

PMID- 23547289
TI  - Genomics: Unknown polypeptides galore.

PMID- 23547290
TI  - Retracted: "Hydrogeochemical behavior of arsenic-enriched groundwater in the
      deltaic environment: comparison between two study sites in West Bengal, India"
      [Journal of Contaminant Hydrology 99 (2008) 22-30].

PMID- 23547291
TI  - Sequencing: Sequencing down the line.

PMID- 23547292
TI  - Sensors and probes: All-in-one optogenetics.

PMID- 23547293
TI  - Targeted proteomics.

PMID- 23547294
TI  - Mass spectrometry-based targeted proteomics.

PMID- 23547295
TI  - Italy's health system reforms on hold.

PMID- 23547296
TI  - The USA and global health diplomacy: goals and challenges.

PMID- 23547297
TI  - CASMI promises to boost productivity of medical R&D.

PMID- 23547298
TI  - Europe: good, bad, and beautiful.

PMID- 23547299
TI  - Spinal cord stimulation in cluster headache.
AB  - Neurostimulation techniques for the treatment of primary headache syndromes,
      particularly for chronic cluster headache (CCH), have received much interest in
      the recent years. Occipital nerve stimulation (ONS) has yielded favourable
      clinical results, and is becoming a routine treatment for refractory chronic
      cluster headache in specialized centres. Meanwhile, other promising techniques,
      such as spinal cord stimulation (SCS) or sphenopalatine ganglion stimulation, are
      emerging. This article reviews the current state of clinical research for
      neurostimulation techniques for chronic cluster headache, and particularly the
      pros and cons of SCS and ONS.

PMID- 23547300
TI  - NS3 genetic variability in HCV genotype-1b isolates from liver specimens and
      blood samples of treatment-naive patients with chronic hepatitis C.
AB  - BACKGROUND: Two distinct inhibitors of the HCV protease have been approved for
      the treatment of patients infected with HCV genotype-1. These drugs are highly
      efficient in suppressing HCV replication; however, their use is limited by the
      emergence of viral mutants resistant to them after a very short time of
      treatment. By analysing blood samples, it was shown that viral strains resistant
      to protease inhibitors (PIs) may exist prior to treatment. The aim of this study
      was to investigate the presence of viral variants resistant to PIs in isolates
      from liver and blood of HCV patients naive to any antiviral therapy. METHODS:
      Liver and blood HCV genotype-1b isolates from 10 patients with chronic hepatitis
      were analysed by cloning and sequencing procedures. RESULTS: The analyses of 10
      15 clones from liver isolates of each patient showed that 7/10 cases had single
      or multiple mutations potentially conferring resistance to PIs. However, the
      analysis of the corresponding blood samples excluded the presence of these
      mutations in all cases but one, which had the Q80R mutation in all clones from
      both liver and plasma samples. No PI-resistant variants were detected in isolates
      from either liver or plasma samples of three patients. CONCLUSIONS: Naturally
      occurring HCV variants resistant to PIs are commonly present at the intrahepatic
      level and this clearly explains their usual, very early emergence under
      treatment; however, the identification of these variants as circulating viral
      populations is not unusual in untreated patients.

PMID- 23547301
TI  - [General health checks--again].

PMID- 23547302
TI  - [General health checks--again. Reply].

PMID- 23547303
TI  - Nail stem cells.
AB  - Our knowledge on stem cells of the hair follicle has increased exponentially
      after the bulge was characterized as the stem cell niche two decades ago. In
      contrast, little is known about stem cells in the nail unit. Whereas hair
      follicles are plentiful and easy to access, the human body has only twenty nails
      and they are rarely biopsied. Therefore, examining fetal material offers unique
      advantages. In the following mini-review, our current knowledge on nail stem
      cells is summarized and analogies to the hair follicle stem cells are drawn.

PMID- 23547304
TI  - [Prohibition convention against nuclear weapons].

PMID- 23547306
TI  - "Through the valley of dry bones".

PMID- 23547305
TI  - Adherence challenges and long-acting injectable antipsychotic treatment in
      patients with schizophrenia.
AB  - Medication nonadherence has been associated with persistence of psychotic
      symptoms, relapse, and hospitalization in patients with schizophrenia. Patients
      with untreated psychosis are significantly less likely to achieve remission,
      whereas antipsychotic drug adherence has been associated with recovery. As such,
      adherence to antipsychotic drug treatment is a key issue for nurses and treatment
      team members caring for patients who typically are on chronic, progressive
      disease course. Long-acting injectable (LAI) anti-psychotic drugs, developed to
      improve adherence and provide and alternative antipsychotic drug treatment fro
      schizophrenia, have been associated with improved treatment outcomes including
      reduction of relapse rates approximately 30% and reduction in hospitalizations.
      However, LAI antipsychotic drugs remain underutilized in the United States
      despite a growing body of literature supporting positive outcomes of LAI versus
      oral antipsychotic drugs. Mental health nurses are in a key position to support
      improved adherence inpatients with schizophrenia through use of practical
      educational strategies that help patients, family members, and health care
      providers better understand and manage treatment.

PMID- 23547307
TI  - Bone densitometry and clinical decision making.

PMID- 23547308
TI  - The role of bone densitometry in the diagnosis and management of the severely
      burned patient with bone loss.
AB  - Children and adults who suffer severe burn injuries develop abnormalities in bone
      and mineral metabolism. The most prominent of these is a reduction in bone
      formation. Events occurring immediately following burn injury that are likely
      contributors to the reduced bone formation include an increase in endogenous
      glucocorticoid production, functional growth hormone deficiency,
      hypoparathyroidism, and interoperative immobilization. The proinflammatory
      cytokines interleukin-1 beta and interleukin-6 may also contribute. To date, the
      effects of burn injury on bone formation have been equivocal. However, the major
      reduction in bone formation without any consistent change in resorption suggests
      an uncoupling of formation and resorption. A consequence of this is lumbar spine
      bone loss as detected by dual-energy X-ray absorptiometry by 6 wk postburn. In
      both cross-sectional and longitudinal studies, the initial low bone density
      remains decreased in relation to unburned age-matched peers. The reduced bone
      density increases the risk for postburn fractures and for reduced peak bone mass,
      increasing the risk of these patients for adult-onset osteoporosis.

PMID- 23547309
TI  - Evaluation of Lunar small animal software for measuring bone mineral content in
      excised rat bones.
AB  - The purpose of this study was to evaluate software from Lunar Corporation
      (Madison, WI) designed for the measurement of bone mineral content ([BMC],g) in
      excised rat femurs using dual-energy X-ray absorptiometry (DXA). Femurs were
      harvested from intact 2- to 12-mo-old female Sprague-Dawley rats, stripped of
      soft tissues, wrapped in saline-soaked gauze, and frozen at -20 degrees F. Thawed
      bones were scanned in air on a 1.7-cm-thick Lucite plate that was laid on the
      manufacturer's supplied Delrin platform. Bones were in an anteroposterior
      position and scanned in a proximal-to-distal manner. Small animal software
      version 1.0d was used with a Lunar DPX-L densitometer. Regions of interest (ROIs)
      were the middle one-third of the diaphysis, a small central area of the distal
      metaphysis, and the total bone. Precision (n = 6 femurs) was calculated for each
      region of interest. After DXA scanning, one group of bones (n = 10 femurs) was
      dried and incinerated in a muffle furnace to obtain bone ash. The ash was then
      digested in acid and aliquots assayed for calcium using atomic absorption
      spectrophotometry. This group of bones was used to correlate BMC with ash weight
      and areal bone mineral density (BMD) with calcium concentration. A second group
      of bones (n = 14 femurs) was used to correlate BMC with maximal load to failure
      (N), a biomechanical variable that provides information about bone strength.
      Precision of repetitive measurements for the three ROIs was 1.2, 3.0, and 0.65%,
      respectively. Total femur BMC and total femur ash weights were significantly
      correlated (r = 0.974, p <0.0001). Total femur area BMD (g/cm2) was significantly
      correlated with calcium concentration (microM) of the bone hydrolysate (r =
      0.686, p = 0.029). Total femur BMC and maximum load to midshaft fracture were
      also significantly correlated (r = 0.914, p<0.0001). The greatest problem with
      the software was with edge detection: operator intervention was necessary to
      place edges manually during scan analyses. We conclude that the small animal
      software from Lunar Corporation accurately and precisely measured BMC in excised
      rat femurs. However, poor edge detection resulted in tedious and time-consuming
      analyses.

PMID- 23547310
TI  - A new X-ray based osteoporosis screening tool provides accurate and precise
      assessment of phalanx bone mineral content.
AB  - Many devices currently available for the assessment of osteoporosis require a
      significant capital investment, are not portable, and require specially trained
      operators. The objective of this study was to assess the accuracy and precision
      of a new tabletop dual-energy computed digital absorptiometry (CDA) device
      (accuDEXA, Schick Technologies, Long Island City, NY) designed to automatically
      and instantaneously assess bone mineral content (BMC) and bone mineral density
      (BMD) of the middle finger. BMC and BMD of 26 cadaveric forearms were measured by
      dual-energy X-ray absorptiometry, radiographic absorptiometry (RA), and CDA.
      accuDEXA measurements were repeated five times with and without repositioning on
      10 forearms. The portion of the finger evaluated by accuDEXA was then excised,
      measurements of the specimen were again obtained using the accuDEXA device, and
      the specimen was incinerated to determine ash weight. BMC assessed by accuDEXA
      and by RA were strongly correlated with ash weight of the excised phalanx
      specimens (r2 = 0.94 and r2 = 0.96, respectively). Short-term precision for BMD
      assessed by the accuDEXA device was 0.9% without repositioning, and 1.8% with
      repositioning. BMD determined by the accuDEXA device was strongly correlated with
      BMD of the hand and forearm (r2 = 0.56-0.69). Dual-energy CDA is a new bone
      densitometry technique that provides rapid, precise, and accurate measurements of
      the middle phalanx of the third finger. The technique may be useful for
      widespread testing of osteoporotic patients.

PMID- 23547311
TI  - Ultrasound measurements of the calcaneus: effects of ethnicity.
AB  - This study investigated whether there were differences in quantitative ultrasound
      (QUS) of the calcaneus between African-American and Caucasian females. QUS-1X, an
      ultrasonometer by Metra Biosystems Inc., was used to determine broadband
      ultrasound attenuation (UBI-4) using Burg Spectral Estimation in
      decibels/megahertz. The average transit time through the heel (TTH) in
      microseconds was used to estimate bone size. A multiple factor index taking into
      account bone size, UBI-4T, was calculated by dividing UBI-4 by TTH in
      decibels/(Megahertz x microseconds). Results showed that premenopausal Caucasian
      females (n = 37) have approx 6-8% lower values (p < 0.05) of QUS indices than
      their African-American (n = 54) counterparts. However, after adjusting for bone
      size, the differences in attenuation disappeared. Pilot data for males
      (Caucasian: n = 16, African-American: n = 18) suggest that the differences in QUS
      appear to be related to bone size. The limited scope of our study supports the
      fact that there are differences in QUS between premenopausal Caucasian and
      African-American females, but not with the same magnitude as evidenced by dual X
      ray absorptiometry. We recommend that more data be collected on ethnic
      differences across all age ranges, to help understand how QUS may be used to
      assess bone mass and determine its value either as a screening tool to diagnose
      low bone mass or as a tool to predict osteoporotic fracture within various ethnic
      groups.

PMID- 23547312
TI  - The use of different dual X-ray absorptiometry brands in a multicenter clinical
      trial: consequences and limits.
AB  - Accurate cross-calibration (CC) and quality control (QC) programs for dual X-ray
      absorptiometry (DXA) instruments are necessary in order to guarantee appropriate
      measurements of bone mineral density (BMD) during longitudinal studies. This
      article details the CC-QC program established for the STRATOS study, a
      multicenter clinical trial investigating the effects of strontium ranelate on
      osteoporotic women with vertebral fractures. Forty-five DXA instruments of
      different brands (namely, 27 Hologic, 9 Lunar, 5 Norland, and 4 Sopha) were cross
      calibrated at the beginning of the study. Twenty-seven of these were still in use
      by the end of the study. The CC was performed at the beginning and at the end of
      the study by measuring a unique spine phantom 20 times. The in vitro
      reproducibility of measurements. (coefficient of variation [CV]) was calculated
      from the results of the phantom measurements. The in vivo CV was obtained from
      pairs of measurements of the lumbar spine and the hip of the patients at the time
      of inclusion in the study. Initial in vitro CV averaged 0.5%. At the end of the
      study, the CC performed for the 27 apparatus in use at the end of the trial
      provided long-term intrabrand in vitro CV of 0.7% for the Hologic (n = 18), 1%
      for the Lunar (n = 5), and 0.3% for the Norland (n = 4) DXA instruments. The in
      vivo short-term CV for the lumbar spine BMD measurements was suboptimal, as
      opposed to the hip measurements, and was most likely due to the age of the
      population investigated. The results of measurements of multibrand DXA apparatus
      in this multicenter study suggest several practical conclusions: (1) the CC
      should be performed by using a single phantom independent of the DXA brand
      tested; (2) duplicate measurements should be performed at the time of patient
      inclusion; (3) the most efficient QC program should include CC, central reading
      of in vivo scans, and central review of daily QC.

PMID- 23547314
TI  - Images in densitometry: cervical osteoporosis.

PMID- 23547313
TI  - Calvarial doughnut lesions associated with high-turnover osteoporosis presenting
      in childhood.
AB  - Osteogenesis imperfecta and juvenile osteoporosis are two well-described
      syndromes of osteoporosis presenting in childhood. There are also several
      references in the radiology literature to calvarial doughnut lesions (CDLs),
      areas of radiolucency surrounded by a dense and well-defined area of sclerotic
      bone, either as an incidental finding or associated with childhood fracture. We
      have characterized the metabolic abnormalities in a 13-yr-old boy with CDLs and
      multiple fractures and followed him during his progression through puberty. The
      patient's paternal grandmother; father; and paternal aunt, uncle, and first
      cousin were similarly affected, and a mandibular lesion in the uncle was
      pathologically described as fibrous dysplasia. The subject's physical examination
      was significant for bony protuberances of the skull and normal hearing, sclearal
      hue, dentition, and joint flexibility. Radiographs revealed calvarial CDLs and
      osteopenia which was confirmed by bone mineral density (BMD) testing. Biochemical
      markers of bone formation and resorption were elevated compared to normal adult
      and a transiliac crest bone biopsy confirmed high-turnover osteoporosis. Over 6
      yr, with no specific therapy, BMD gradually normalized, but the CDLs increased in
      size, bone turnover remained elevated by biochemical markers, and he continued to
      fracture. The subject's affected father and maternal grandmother had normal BMD
      and no history of adult fracture. CDLs with high-turnover osteoporosis should be
      considered in the differential diagnosis of pediatric osteoporosis. During
      puberty the BMD normalizes but the high-turnover state persists, and the
      propensity to fracture eventually decreases in older affected adults. The CDLs
      may be a variant of fibrous dysplasia, and further study is necessary in order to
      elucidate the stimulus for increased bone turnover and the familial nature of
      this syndrome.

PMID- 23547315
TI  - Linkage, association, and the genetic analysis of bone mineral density and
      related phenotypes: an overview for clinicians.
AB  - Most medical genetic studies seek to answer one of two questions: What genes are
      important in determining disease risk? and What alleles of a candidate gene
      confer excess risk? This article seeks to provide physicians with a practical
      approach to assessing articles on genetic topics, using examples from bone
      mineral density and related areas. First, this article reviews the essential
      features of meiosis, crossing over, and allele detection. Second, mapping
      strategies are described and illustrated. Third, this article considers studies
      of the association between alleles of specific candidate genes and bone
      phenotypes. Linkage without association and association without linkage are both
      possible. Fourth, the ability of studies using inbred mice to establish both
      linkage and association is explained. Fifth, the transmission disequilibrium test
      is proposed as a superior design for investigating the association of alleles
      with bone phenotypes. Sixth and last, a systematic approach to reading medical
      genetic studies critically is developed. Common shortcomings in published
      articles include insufficient evidence for candidate choice, confusion between
      functionally significant alleles and markers, and failure to distinguish between
      identity by descent and identity by state.

PMID- 23547316
TI  - Osteoporosis in earlier human populations.
AB  - Skeletons excavated from archeological sites form a rich resource for research
      into ancient disease. This article takes the form of a brief review of some of
      the work that has been conducted on osteoporosis in past populations using
      collections of ancient skeletons. It is clear from this work that osteoporosis
      has a long history in humankind.

PMID- 23547317
TI  - Causes of secondary osteoporosis.
AB  - Primary osteoporosis associated with menopause and aging is by far the most
      frequent metabolic bone disease. However, there are many patients who present
      with secondary osteoporosis due to identifiable causal factors and many others in
      whom a secondary factor contributes to the severity or progression of primary
      osteoporosis. Recognition of these secondary causes is particularly important for
      the prevention of further vertebral fractures, which are often progressive in
      secondary osteoporosis. This review will summarize the major factors that cause
      secondary osteoporosis and will discuss their pathogenetic mechanisms. While the
      most frequent cause is glucocorticoid excess, a number of other diseases, as well
      as drugs and nutritional deficiencies, can cause secondary osteoporosis. It is
      important to identify secondary osteoporosis both because of the differences in
      clinical expression due to different pathogenetic mechanisms and because there
      are often effective interventions that can add to the more general approach used
      in primary osteoporosis.

PMID- 23547318
TI  - Martin A. Swerdlow, MD (1923-2012).

PMID- 23547319
TI  - Franz von Lichtenberg (1920-2012).

PMID- 23547320
TI  - Flow cytometry criteria for systemic mastocytosis: bone marrow mast cell counts
      do not always count.

PMID- 23547321
TI  - The authors' reply.

PMID- 23547322
TI  - More than half a million California adults seriously thought about suicide in the
      past year.
AB  - In 2009, nearly 2.4 million adults in California reported having seriously
      thought about suicide during their lifetimes. Among these adults, more than half
      a million had thought seriously about suicide sometime during the past year.
      Members of sexual minorities were almost three times as likely as all adults in
      California to have had suicidal thoughts during the past year. This policy brief,
      based on data from the 2009 California Health Interview Survey (CHIS), presents a
      comprehensive overview of risk factors associated with suicidal thoughts among
      adults ages 18 and older and highlights differences in suicidal ideation among
      demographic groups and geographic regions in California.

PMID- 23547323
TI  - [Not Available].

PMID- 23547324
TI  - The effects of California's paid family leave program on mothers' leave-taking
      and subsequent labor market outcomes.
AB  - This analysis uses March Current Population Survey data from 1999 to 2010 and a
      differences-in-differences approach to examine how California's first in the
      nation paid family leave (PFL) program affected leave-taking by mothers following
      childbirth, as well as subsequent labor market outcomes. We obtain robust
      evidence that the California program doubled the overall use of maternity leave,
      increasing it from an average of three to six weeks for new mothers--with some
      evidence of particularly large growth for less advantaged groups. We also provide
      evidence that PFL increased the usual weekly work hours of employed mothers of 1-
      to 3-year-old children by 10 to 17 percent and that their wage incomes may have
      risen by a similar amount.

PMID- 23547325
TI  - High-tech health care: lawmakers are building up telehealth by breaking down
      barriers.

PMID- 23547326
TI  - The heat is on: a new way to identify areas with large numbers of high-cost
      Medicaid patients may improve their health while saving states money.

PMID- 23547327
TI  - Legally green: the nation is watching closely as Colorado and Washington put new
      pot laws in place.

PMID- 23547328
TI  - It's go time: states have only a few months to get their health insurance
      exchanges up and running.

PMID- 23547329
TI  - What you should know: salmonella and listeria and E. coli--oh my!

PMID- 23547330
TI  - Resident rounds. Part III: Multicentric reticulohistiocytosis presenting as
      granuloma annulare.

PMID- 23547331
TI  - Practical aspects of topical corticosteroid selection.

PMID- 23547332
TI  - Not all topical corticosteroids are created equal! Optimizing therapeutic
      outcomes through better understanding of vehicle formulations, compound
      selection,and methods of application.
AB  - Since the first successful topical glucocorticosteroid, compound F, was applied
      to human skin to treat eczematous dermatitis approximately 60 years ago, several
      advances have been made in the development of topical corticosteroid (TC)
      compounds and vehicle formulations. The ability to apply a TC and improve skin
      disease revolutionized dermatologic therapy and has proven to be one of the
      biggest advances in the history of dermatology. The potency of a TC and their
      vehicle formulation can vary among brand and generic TC compounds, which can
      sometimes confound the clinical situation as one brand or generic formulation of
      a TC may be well tolerated while another generic formulation induced skin
      irritation or allergenicity in a patient who previously encountered no
      difficulties.

PMID- 23547333
TI  - Allergy to topical steroids.
AB  - Topical steroid allergy (TSA), as defined by an allergy to either the steroid
      molecule itself or to an ingredient in the vehicle, is common in clinical
      practice, but it is rarely diagnosed. This article elucidates the difficulties
      involved in clinically recognizing TSA, and also the appropriate protocols for
      its diagnosis and treatment.

PMID- 23547334
TI  - Reply: To PMID 22623539.

PMID- 23547335
TI  - Implementing the Affordable Care Act: choosing an essential health benefits
      benchmark plan.
AB  - To improve the adequacy of private health insurance, the Affordable Care Act
      requires insurers to cover a minimum set of medical benefits, known as "essential
      health benefits." In implementing this requirement, states were asked to select a
      "benchmark plan" to serve as a reference point. This issue brief examines state
      action to select an essential health benefits benchmark plan and finds that 24
      states and the District of Columbia selected a plan. All but five states will
      have a small-group plan as their benchmark. Each state, whether or not it made a
      benchmark selection, will have a set of essential health benefits that reflects
      local, employer-based health insurance coverage currently sold in the state.
      States adopted a variety of approaches to selecting a benchmark, including
      intergov-ernmental collaboration, stakeholder engagement, and research on
      benchmark options.

PMID- 23547336
TI  - Paying for value: replacing Medicare's sustainable growth rate formula with
      incentives to improve care.
AB  - This brief sets forth a set of policy options to improve the way health care
      providers are paid by Medicare. The authors suggest repealing Medicare's sustain
      able growth rate (SGR) formula for physician fees and replacing it with a pay-for
      value approach that would: 1) increase payments over time only for physicians and
      other provid-ers who participate in innovative care arrangements; 2) strengthen
      primary care and care teams; and 3) implement bundled payments for hospital
      related care. These reforms would be adopted by Medicare, Medicaid, and private
      plans in the new insurance marketplaces, with the goal of accelerating innovation
      in care delivery throughout the health system. Together, these policies could
      more than offset the cost of repealing the SGR formula, saving $788 billion for
      the federal government over 10 years and $1.3 trillion nationwide. Savings also
      would accrue to state and local governments ($163 billion), private employ-ers
      ($91 billion), and households ($291 billion).

PMID- 23547337
TI  - Insurers' medical loss ratios and quality improvement spending in 2011.
AB  - The Affordable Care Act's medical loss ratio (MLR) regulation requires insurers
      to spend 80 percent or 85 percent of premiums on medical claims and quality
      improvements. In 2011, insurers falling below this minimum paid more than $1
      billion in rebates. This brief examines how insurers spend their premium dollars-
      particularly their investment in quality improvement activities--focusing on
      differences among insurers based on corporate traits. In the aggregate, insurers
      paid less than 1 percent of premiums on either MLR rebates or quality improvement
      activities in 2011, with amounts varying by insurer type. Publicly traded
      insurers had significantly lower MLRs in each market segment (individual, small
      group, and large group), and were more likely to owe a rebate in most segments
      compared with non-publicly traded insurers. The median quality improvement
      expenditure per member among nonprofit and provider-sponsored insurers was more
      than the median among for-profit and non-provider-sponsored insurers.

PMID- 23547359
TI  - [Sexology: individuality in question].

PMID- 23547360
TI  - [Acquiring a sexual identity].
AB  - Progressive acquisition from childhood onwards to adulthood of a procreative and
      psycho-emotional sexual identity is presented in all its bio-psycho-social
      complexity. Gender identity disorders (GDI) and the different sexual orientations
      (hetero-, homo- or bisexual) are included with their possible etiologies.
      Different medico-psycho-social programs and projects are presented targeting
      persons having difficulties in this developmental process of their identity.

PMID- 23547361
TI  - [Sexuality between emotions and sensations].
AB  - All sexual activity seems to revolve around a mix of sensations and feelings. The
      complexity of this combination sometimes makes it difficult to determine which
      aspect predominates. Other times, on the contrary, it is very clear which one
      plays the main role. In addition comes the question of the level of consciousness
      implicated in a possible confrontation between reality and imaginary, reality and
      dreams.

PMID- 23547362
TI  - [Sexuality and cardiac arrhythmias].
AB  - For most patients, sexual activity represents a low risk of triggering cardiac
      arrhythmias. However, particularly in patients with an underlying heart disease,
      sexual activity may cause cardiac arrhythmias which may be sometimes serious.
      From a physiological point of view, sexual activity produces increased
      sympathetic activity and thereby probably reduced vagal tone which at different
      degrees may induce cardiac arrythmias. Several presently available autopsy
      studies have shown that this happens very rarely and that it mostly affects men.
      Finally, recently published recommendations allow us to better advise patients
      with cardiac arrhytmias to engage in sexual activity or to defer it until the
      condition is stabilized and optimally controlled.

PMID- 23547363
TI  - [Desire disorders in the couple: accident, dream, sexuality].
AB  - Eros, as few only would doubt about it, takes part in the deepest and most
      intimate area of the human being. Our contemporaries attach great importance to
      sexuality, but feed the illusion that mastering it could lead to miracles in the
      couple. We suggest that giving up control and committing himself to fully
      listening to the patient, the physician will be able to orient him in the blind
      rules of desire and to accept fortuity. Unexpected (?) accident, dream, hypnosis,
      often powerfully catalyze changes. Some clinical situations are described in this
      article with their evolution as consultations develop, without foreseeing their
      interpretation.

PMID- 23547364
TI  - [Sexuality, heart and chocolate].
AB  - All along the history, many kinds of magic and aphrodisiac properties were
      attributed to the chocolate. Because of the presence of certain active
      substances, cacao and chocolate are supposed to have some potentially beneficial
      effects on human health, particularly on cardiovascular system. Containing
      flavoniods, cacao and its products have antioxidant, anti-inflammatory, anti
      atherogenic, anti-thrombotic, antihypertensive and neuroprotective effects, as
      well as influence on insulin sensitivity, vascular endothelial function, and
      activation of nitric oxide. Other molecules, like methyxantin, biogenic amines
      and cannabinoid-like fatty acids, may have a psychoactive action. Synergic effect
      of all these substances could have a positive direct and indirect influence on
      sexual health and function. Nevertheless, randomized studies are needed to
      confirm these hypotheses and to elaborate recommendations about cacao
      consumption.

PMID- 23547365
TI  - [Sexuality, morphology and body weight].
AB  - The body is the place where the dimensions of space, time, subjectivity and
      objectivity meet and interact. These dimensions are considered with regard to
      eating, sleeping and sex within the couple. When a disfunctioning appears in one
      of these three fundamental aspects, it is, in general, treated alone. Eating,
      sleeping and sex are, on the contrary, interdependant, and in this perspective, a
      therapeutical intervention on one of these vital functions can lead to an
      amelioration of another one of them.

PMID- 23547366
TI  - [Renal glucosuria].
AB  - The occurrence of glucosuria in the absence of hyperglycemia is distinctive for
      renal glucosuria. SGLT2 mutations provoke familial renal glucosuria characterized
      by persistent glucosuria in the absence of any other renal tubular dysfunction.
      Renal glucosuria associated with others proximal tubular dysfunctions points to
      Fanconi syndrome. This generalized dysfunction of proximal tubule needs to be
      treated and may progress regarding its aetiology to chronic renal failure. The
      development and study of models of Fanconi syndrome has recently contributed to a
      better knowledge of the mechanisms implicated in the tubular transport of glucose
      and low-molecular-weight-proteins. This article reviews these recent
      developments.

PMID- 23547367
TI  - [France powerless against "sexual assistants"].

PMID- 23547368
TI  - [Traveling...Excerpts from the log, training in obstetrics and gynecology,
      Nicaragua].

PMID- 23547369
TI  - [High coronary risk: better to evaluate in primary prevention].

PMID- 23547370
TI  - [The latest diagnostics of Dr. House (9)].

PMID- 23547371
TI  - [The danger of good intentions].

PMID- 23547372
TI  - [Identification of Nam Dinh virus in China].
AB  - During 2009-2012, the Nam Dinh virus (NDiv) was detected from the samples of
      Culex pipiens quinquefasciatus in Shenzhen China. In this study, cell
      culture,SYBR Green I based real time RT-PCR and RT-PCR were performed to analyze
      the cell susceptibility and other biological characteristics of the NDiV
      isolates. The results showed that C6/36 cell line was susceptible to four
      isolates of Culex pipiens quinquefasciatus. The "S" type amplification curve and
      specific melting curve were obtained in the realtime fluorescence quantitative RT
      PCR based on SYBR Green I for the detection of the NDiV from the mosquito. The
      target bands from the RdRp gene and partial fragment of ZmHel1 gene were observed
      using agarose gel electrophoresis. Both the nucleotide and amino acid sequences
      of four Shenzhen isolates showed more than 99.00% homology with the Vietnam
      representative NDiV strain (02VN178). Phylogenetic analysis showed that four
      Shenzhen isolates shared the same evolution branch as the Vietnam representative
      NDiV strain. This is the first report of NDiV in China.

PMID- 23547374
TI  - [Development of real-time fluorescent quantitative PCR method for detecting
      Bombyx mori cytoplasmic polyhedrosis virus].
AB  - A pair of specific primers were designed according to the published 118 bp
      conserved sequence of polyhedrin gene of Bombyx mori cytoplasmic polyhedrosis
      virus (BmCPV) in GenBank and a serial dilutions of a recombinant plasmid were
      prepared and used to generate standard curves, to establish a real-time
      fluorescent quantitative PCR method for detection of BmCPV. The results showed
      that the linear relationship between virus concentration (X) and Ct (Y) was Y = 
      3. 582 lgX + 38.748 with the correlation coefficient R2 = 0999. The method was
      very sensitive, specific and reproducible. It can be applied in the rapid
      detection of BmCPV and the prevalence investigation of this disease.

PMID- 23547373
TI  - [Establishment of mammalian cell lines for constitutive expression of influenza
      virus matrix protein 2].
AB  - To establish a mammalian cell line for stable expression of the matrix protein 2
      (M2) of influenza virus type A. M2 gene was amplified by PCR from the influenza
      virus strain A/PR/8/34. The PCR product was cloned into eukaryotic expression
      vector pcDNA5/FRT. After identification with restriction enzyme digestion, the
      plasmid was co-transfected with plasmid pOG44 which expressed Flp in Flp-In-CHO
      cells. The target gene was integrated into chromosome of CHO cells by homologous
      recombination in vivo. Recombinant CHO-M2 cell lines were selected for hygromycin
      B resistance. A total of 15 recombinant cell strains with high expression of M2
      protein were screened by hygromycin, and the expression of M2 protein was
      determined by IFA and Western blot. After subculturing for 10 passages, the
      presence of M2 gene in the CHO-M2 cells was confirmed by PCR, and the expression
      of M2 protein were proved by IFA and Western blot. We successfully constructed a
      mammalian cell line which stably expressed M2 protein of influenza virus type A.
      The cell line will be useful for studies on function of M2 protein and provide
      tools for novel influenza virus vaccine development.

PMID- 23547375
TI  - [Study on using NSP2 protein of porcine reproductive and respiratory syndrome
      virus (HuN4-F112) to express E2 neutralizing epitope of classical swine fever
      virus].
AB  - Establishment of recombinant porcine reproductive and respiratory syndrome virus
      (PRRSV) with co-expression E2 Epitope of Classical Swine Fever virus (CSFV) is a
      crucial step to develop a genetic engineered vaccine against PRRSV and CSFV.
      Reverse genetic manipulation could be adopted as a com monly used technique. In
      this study, we focus on using nonessential regions of NSP2 (aa480-532 and aa508
      532) as viral vector to express E2 Epitope of CSFV. A neutralizing epitope of
      classical swine fever virus (CSFV) E2 protein was inserted into the two
      nonessential region of nsp2 by the method of mutant PCR, basing on the infectious
      clone of HuN4-F112 vaccine strain. The co-expressed full-length cDNA clones (psk
      HuN4-F112-delta508-532 + E2 and psk-HuN4-F112-delta480-532 + E2) were assembled
      by cloning and splice of the gene fragments. The completely assembled full-length
      cDNA clones were confirmed by sequence and Swa I enzyme digestion. Capped RNAs
      were transcribed in vitro from a full-length cDNA clone of the viral genome and
      transfected into BHK-21 cells by liposome to acquire the rescued virus. The
      rescued recombinant viruses were passaged on MARC-145 cells. The successfully
      rescued viruses were tested by RT-PCR, digestion, and genome sequence. The
      results showed that these rescued viruses could be distinguished from the
      parental virus (HuN4-F112) with the mutant genetic marker (Mlu I enzyme site of
      virual genome at 14 667nt was created by synonymous mutation) and the inserted
      nsp2 gene region. The results of IFA showed that the inserted E2 epitope could be
      expressed by the recombinant viruses and the E2 epitope gene was stable during
      the viral serial passage. The results of plaque assay and viral growth curve
      showed that the recovery viruses possessed similar characterses of viral growth
      to those of the parental virus. In summary, the full-length infectious cDNA
      clones containing the marker gene were constructed and the marker recombinant
      viruses were rescued. The results suggested that these stable infectious clones
      could be used as an important tool for development of novel vaccine against
      PRRSV.

PMID- 23547376
TI  - [Construction and immunogenicity analysis of recombinant replication-defective
      human adenovirus type 5 bearing the porcine circovirus type 2 Cap protein gene].
AB  - To construct a recombinant replication-defective human adenovirus type 5
      expressing Cap protein of PCV2 and test the immunological efficacy in mice. In
      this study, the recombinant replication-defective human adenovirus type 5, named
      as rAd5-Cap (wt-rAd5), was constructed through homologous recombination
      internally in the HEK293AD cells after co-transfection of the Pac I-linearized
      backbone plasmid and the shuttle plasmid pacAd5CMV-Cap containing the open
      reading frame (ORF2) of the porcine circovirus type 2 (PCV2) cap protein or
      pacAd5CMV without inserted fragment. Furthermore, the rAd5-Cap could induce the
      expression of PCV2 cap protein in the HEK293AD cells with high efficacy evaluated
      by the RT-PCR and indirect immunofluorescence assay (IFA). The virus titer of
      rAd5-Cap could reach up to 10(8.5) TCID50/mL similarly to that of wt-rAd5,
      indicating that there was little affect on the virus proliferation after the
      insertion of PCV2 cap protein gene. The humeral immune responses could be
      activated and detected 14 days after the inoculation of the mice with 10(7)
      TCID50 rAd5-Cap intramuscularly, and constantly in crease in another 14 days.
      These molecular biological and animal experiments results demonstrated that the
      PCV2 cap protein could be efficiently expressed by the recombinant adenovirus
      rAd5-Cap in eukaryotic cells and induce robust immune responses in mice, which
      laid a good foundation for the development of new type vaccine against porcine
      circovirus.

PMID- 23547377
TI  - [Virological characterization of influenza B virus in mainland China during 2011
      2012].
AB  - In order to understand the prevalence and variation of influenza B viruses, the
      antigenic and genetic characteristics of influenza B viruses circulating in
      Mainland China during April, 2011 to March, 2012 were analyzed. The results
      showed the B Victoria lineage viruses were much more prevalent than B Yamagata
      lineage during this period, phylogenetic analysis showed vast majority of
      Victoria lineage viruses belong to genetic group 1, intra-clade reassortant
      between HA1 and NA gene was identified in a minor proportion of the viruses.
      72.8% of the B/Victoria-lineage viruses were antigenically closely related to the
      vaccine strain B/Brisbane/60/2008. B Yamagata component was not included in the
      trivalent influenza vaccine in China during the study period, however vast
      majority of B Yamagata lineage viruses were antigenically and genetically closely
      related to the representative virus B/Hubei-Wujiagang/158/2009(97.8%) and
      B/Sichuan-Anyue/139/2011(85.2%) in China, reassortant between HA1 and NA was not
      identified in B Yamagata lineage viruses. Overall, the predominant circulating
      influenza B viruses in 2011-2012 season in China were matched by current
      influenza vaccine and the selected representative viruses were proved to
      represent the antigenic and genetic characteristics of the circulating viruses.

PMID- 23547378
TI  - [Utility of high throughput sequencing technology in analyzing the terminal
      sequence of caudovirales bacteriophage genome].
AB  - To confirm the hypothesis that the high frequency sequences of high throughput
      sequencing are the terminal sequences of the bacteriophage genome. An adaptor of
      specific sequence was linked to the end of the bacteriophage T3 genomic DNA,
      which was then subject to high throughput sequencing; as a control, the same T3
      genomic DNA without adaptor was also analyzed by high throughput sequencing. The
      sequencing results were examined with bioinformatics software. Similar high
      throughput sequencing technique was applied to analyze the genomic sequence of N4
      like bacteriophage IME11. Bioinformatics study showed that the sequences tagged
      with adaptors were consistent with the high frequency sequences without adaptor
      labeling. Our analysis also indicated that the end of the T4-like phage genome
      had specific sequences instead of random sequences, disagreeing with the previous
      assertion. Evidences were provided that N4-like bacteriophage had a particular
      terminal sequence: the left end of the genome was unique while the right end was
      permuted. The high throughput sequencing technique was convenient and practical
      to be used to simultaneously detect the terminal sequence and the complete
      sequence of bacteriophage genome.

PMID- 23547379
TI  - [Effect of RelB on HIV-1 Vpr-mediated transcription activation and cell G2/M
      arrest].
AB  - Vpr, an auxiliary protein of HIV-1(Human immunodeficiency virus type 1), exerts
      important functions to promote viral replication and AIDS progression. In this
      study, we performed a yeast two-hybrid screening assay using human cDNA library
      to further investigate the molecular mechanism of various functions of Vpr RelB,
      a key protein in NF-kappaB signaling pathway, was identified as a Vpr interaction
      protein by co-immunoprecipitation. Further investigations indicated that RelB not
      only promoted the Vpr-mediated activation of NF-kappaB reporter gene, but also
      enhanced the transactivation of HIV LTR. Moreover, the results showed that RelB
      promoted Vpr-induced cell cycle G2/M arrest. Collectively, these results
      indicated that RelB might interact with Vpr and regulate its transcriptional
      activation and cell cycle arrest.

PMID- 23547381
TI  - [Human bocavirus and its current epidemic status in China].
AB  - Human bocavirus (HBoV) is classified in the family of parvovirdae, genus
      bocavirus. Besides parvovirus B19 and human parvovirus 4 (PARV4), HBoV isone of
      the parvoviruses currently known to infect and cause illness in human. So far,
      four different HBoVs (HBoV1-4) have been successively reported. The incidence of
      HBoVs infection varies widely, the clinical presentations of patients are
      different, and HBoVs are often co-detected with other pathogens. There are
      already quite a few report of HBoVs infection, and this article reviews and
      discusses the biological characters, epidemic characters, pathogenic mechanism,
      phylogenetic analyses of HBoVs and the epidemiological situation in China.

PMID- 23547380
TI  - [Genotype features of norovirus associated with acute gastroenteritis through
      sentinel surveillance in Guizhou Province, 2011].
AB  - To study the genotype of Norovirus associated with acute gastroenteritis in
      Guizhou Province 2011, the patients' fecal specimens were collected from the
      Guizhou Province People's Hospital in the period of May to December 2011.
      Noroviruses in specimens were detected by a real-time reverse transcription
      polymerase chain reaction (Real-time RT-PCR). VP1 genes of norovirus-positive
      strains were then cloned and sequenced. Out of 70 clinical samples, the positive
      rates for norovirus G I (1 strain) and G II (34 strains) were 1.43% and 48.57,
      respectively. The VP1 sequencing results of seven norovirus G II showed thatthree
      strains were genotype G II . 4 and four strains were genotype G II . 3 Those
      genotype GIL . 4 strains were new variants (GII . 4 2011),closest to GII . 4
      2006b variant. One amino acid appeared back mutation. Those genotype G II . 3
      strains were divided into 2 gene clusters. One cluster was closest to Korean
      strain (HM635118) and Shanghai strain(GU991355). One cluster was closest to
      Japaness strain (AB629943) and 2007 Indian strain (EU921389), Four amino acids
      appeared back mutations.

PMID- 23547382
TI  - [Advances in recently identified coronaviruses].
AB  - Coronaviruses are a large family of viruses which include viruses that cause the
      common cold and severe acute respiratory syndrome (SARS) in humans and other
      diseases in animals. There are considerable genetic diversities within
      coronaviruses due to their wide rang hosts and their special gene replication and
      transcription mechanisms. During this process, gene recombinations often occur,
      resulting in novel subtype or coronavirus emerge constantly. Of note are SARS
      like-CoVs and novel HCoV-EMC identified in 2012. This minireview summarized major
      advances of recently identified coronaviruses, focusing on the genome structures
      and interspecies jumping mechanism of coronavirus.

PMID- 23547383
TI  - [Research progress of the molecule mechanisms of Ebola virus infection of cells].
AB  - Ebola virus can cause severe Ebola hemorrhagic fever. The mortality rate is 90
      percent. Up till now, there is no effective vaccine or treatment of Ebola virus
      infection. Relaed researches on Ebola virus have become a hot topic in virology.
      The understanding of molecular mechanisms of Ebola virus infection of cells are
      important for the development of vaccine and anti-virus drugs. Therefore, this
      review summarized the recent research progress on the mechanisms of Ebola virus
      infection.

PMID- 23547384
TI  - [Cell autophagy and virus infection].
AB  - Autophagy is a catabolic process including self-degradation of intracellular
      components via the lysosomal machinery. The biological behavior can be regarded
      as defense mechanism, maintaining the cell growth, metabolism and homeostasis
      etc. To date, plenty of autophagy related genes have been identified. In
      addition, it has been recognized that autophagy plays important roles in the
      context of virus infection: it can transport viruses from cytoplasm to lysosome
      to degrade viruses; it can transfer viral nucleic acid to intracellular sensors
      to activate innate immunity; it can also present viral antigens to MHC class II
      molecules to activate adaptive immune responses. Autophagy may serve as a double
      edged sword to intracellular pathogens. On one side, autophagy may degrade and
      clear invading microorganisms by xenophagy; on the other side, some
      microorganisms may develop mechanisms to escape from autophagy for their
      survival. In this paper, the notion of autophay and the function of autophagy
      related genes are reviewed. Furthermore, the association of autophagy with a
      variety of viruses is discussed.

PMID- 23547385
TI  - [Modulation of host immune defenses by cytomegalovirus: advanced insights from
      evolutionary game theory].
AB  - Human cytomegalovirus (HCMV) is an ubiquitous pathogen that infects a majority of
      the world's population. The virus can establish lifelong infection once the human
      body is infected by HCMV and virus can be reactivated from a latent state in
      immune suppressed individuals. HCMV has developed several strategies to evade
      host immune surveillance after millions of years of co-evolution with mankind.
      One of the classical tricks is encoding homologous to human immune factors or
      stealing host cellular genes that have significant functions in immune system.
      Virus encoded immune modulators which participate in regulating the major
      histocompatibility complex, cellular immunity, humoral immunity, cytokines and
      chemokines are supposed to play a significant role in the pathogenesis of HCMV.
      Evaluation of "mutually assured survival" relationship between virus and host
      provides important insights into viral immunopathogenesis and study of viral
      immunomodulatory proteins might help us to uncover new human genes that control
      immunity.

PMID- 23547387
TI  - [Address by the rector of the Pomeranian Medical University in Szczecin
      inaugurating the academic year of 2011/2012].

PMID- 23547386
TI  - [Detection methods for retroviruses and reverse transcriptase: commentary].
AB  - Retroviruses are often used as a carrier for expression of target protein or
      chimeric target gene. Although non-infectious viruses are selected in the
      laboratory, it does not exclude harms form these viruses. The monitoring and
      detection of retroviruses has a very important significance. Reverse
      transcriptase activity is an important indicator of retrovirus replication.
      Herein, methods for detection of retroviruses and reverse transcriptase are
      reviewed for further research references.

PMID- 23547388
TI  - [Some aspects of idiopathic myopathies of childhood].
AB  - Juvenile idiopathic myopathies are rare chronic autoimmune diseases with proximal
      muscle weakness and typical skin lesions. Juvenile dermatomyositis is the most
      common childhood myopathy. Juvenile idiopathic myopathies differ from adult-onset
      forms as regards prevalence, course, clinical picture, and very rare coincidence
      with a malignancy. Early diagnosis and combined long-term immunosuppressive
      therapy may significantly improve the prognosis.

PMID- 23547389
TI  - [Management of small bowel obstruction caused by a gallstone].
AB  - Bowel obstruction caused by a gallstone is a rare pathology in the abdomen. The
      high mortality associated with this condition has prompted the authors to present
      their experience over the past two years against the background of published case
      reports. This paper presents three different ways of management of gallstone
      ileus: enterolithotomy; two-stage surgery--enterolithotomy followed by
      cholecystectomy; one-stage surgery--enterolithotomy combined with cholecystectomy
      and fistula repair. The authors report on a case which was successfully managed
      with enterolithotomy only and discuss arguments in favor of each procedure.
      Enterolithotomy appears to be the safest approach in gallstone ileus, leaving
      time to qualify the patient for further surgery on the basis of clinical status
      and symptoms.

PMID- 23547390
TI  - [Some aspects of systemic and localized (limited) sclerosis in children].
AB  - Sclerosis is a rare connective tissue disease. Uncontrolled process of fibrosis
      and collagen accumulation in the tissues leads to functional impairment and
      structural changes in the skin and internal organs. A leading role in the
      pathogenesis of sclerosis is played by the interrelated mechanism of vascular
      injury, immune changes, and fibroblast activation. Fibrosis of the connective
      tissue of the skin and internal organs determines two forms of the disease:
      systemic sclerosis and localized (often called limited) sclerosis. Despite
      similarities in the histopathology of the skin, these two types differ
      fundamentally as to course and prognosis. The prevalence of sclerosis among
      children has not been determined. 2% to 11.5% of adults with systemic sclerosis
      noted the onset of the disease before the age of 16 years. The onset was prior to
      10 years of age in 1% to 2% of adult patients. According to some authors,
      localized sclerosis is found approximately 2.7 per 100,000 thousand of children,
      3 to 4 times more often in girls especially in the preschool and early school
      age. Localized sclerosis is seen 9 to 10 times more often than systemic
      sclerosis. This work discussed diagnostic criteria, differential diagnosis, and
      prognosis of sclerosis in children were.

PMID- 23547391
TI  - [Coexistence of systemic sclerosis and gout? Hyperuricemia in systemic sclerosis:
      case report and literature review].
AB  - INTRODUCTION: There are few reports in the literature on the coexistence of
      systemic sclerosis with gout. Gout is the most common cause of arthritis among
      men past the age of 40 years. Elevated levels of uric acid may be associated with
      the metabolic syndrome, administration of diuretics, and kidney or cardiovascular
      disease. MATERIAL AND METHODS: We present the case of a 47-year-old male who was
      diagnosed with arterial hypertension, hypertrophic cardiomyopathy, systemic
      sclerosis with interstitial lesions in lungs, and hyperuricemia. Large nodules
      resembling tophi were present on the right elbow and knee. Radiographs of these
      sites revealed numerous calcifications. CONCLUSIONS: Coexistence of gout should
      be considered in a patient with systemic sclerosis and hyperuricemia. The authors
      draw attention to the potential effect of elevated levels of uric acid on the
      prognosis, particularly in the context of cardiovascular complications. There are
      data in the literature on the relationship of hyperuricemia with pulmonary
      arterial hypertension in patients with systemic sclerosis.

PMID- 23547392
TI  - [Heart involvement in systemic sclerosis: analysis of four cases].
AB  - INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterized by
      multisystem involvement. Heart involvement occurs in 80-100% of cases and
      represents one of the more common risk factors of death. Myocardial fibrosis and
      vascular microangiopathy lead to arrhythmias and impaired contractility with
      secondary left and right heart failure. Pulmonary arterial hypertension in some
      patients with systemic sclerosis results in right heart failure and low output
      syndrome during the end-stage of the disease. The aim of the present study was to
      analyze four cases of systemic sclerosis with severe cardiovascular complications
      and a fatal outcome. CASE DESCRIPTIONS: Case 1: A 68-year-old female who probably
      suffered from limited SSc (lcSSc) and pulmonary arterial hypertension for more
      than 10 years was unsuccessfully treated with vasodilatators (sildenafil,
      iloprost). Case 2: A 52-year-old female with a 5-year history of diffuse
      cutaneous SSc (dcSSc), interstitial lung disease, and pulmonary arterial
      hypertension underwent aggressive therapy with immunosuppressive and
      antiproliferative (treprostinil) agents but without effect on the progression of
      the disease. Case 3: A 50-year-old male with dcSSc and coexistent cardiomyopathy
      with dominating symptoms of right heart failure was placed on high doses of
      immunosuppressants (i.v. cyclophosphamide) and had a cardioverter-defibrillator
      implanted as part of primary prevention. The patient died with symptoms of
      severe, therapy-resistant, two-sided heart failure. Case 4: A 58-year-old female
      with a 6-year history of dcSSc, interstitial lung disease, and heart involvement
      with severe ventricular arrhythmias and significant mitral and tricuspid
      insufficiency received intensive immunosuppressive therapy (i.v.
      cyclophosphamide) and underwent arrhythmia ablation. Sudden cardiac arrest in
      this patient was attributed to arrhythmia due to cardiomyopathy associated with
      systemic sclerosis. CONCLUSIONS: Lung and heart involvement is the most common
      reason for poor prognosis in systemic sclerosis. Arrhythmias, usually latent
      clinically, and right heart failure associated with cardiomyopathy or pulmonary
      hypertension are the main reasons of cardiac death in SSc patients. Severe and
      fatal cardiovascular complications occur more often in dcSSc, particularly during
      the first few years after diagnosis. Early detection of cardiovascular
      manifestations should be a priority in systemic sclerosis.

PMID- 23547393
TI  - [Level of depression in women undergoing gynecologic surgery].
AB  - STUDY OBJECTIVE: To determine the level of depression in women during the early
      post-operative period. MATERIAL AND METHOD: 220 women treated surgically for
      various gynecologic conditions were enrolled. The study was done between day 4-6
      after surgery using Beck's Depression Inventory (BDI). The results were analyzed
      statistically. RESULTS: It was found that the mean level of depression on the BDI
      scale in the study group of women was 12.24 +/- 8.73. The mean level of
      depression in patients who underwent surgery using the vaginal route was
      significantly greater (p = 0.003) than in patients after laparoscopy and patients
      after laparotomy. CONCLUSIONS: The mean level of depression in the study group
      approached values found in depression. Patients after surgery using the vaginal
      route demonstrated higher levels of depression than patients after laparoscopy.
      Age, education, source of subsistence, and number of children had an impact on
      the level of depression in the study group. Marital status and place of residence
      were without effect on the level of depression in the patients.

PMID- 23547394
TI  - The rationale behind hypofractionated high-dose intensity-modulated radiotherapy
      in patients with localized prostate cancer: short review.
AB  - The use of improved technology has fostered increasing interest in
      hypofractionated radiation therapy for prostate cancer. There also is convincing
      evidence that an unusual aspect of prostate cancer radiobiology allow a different
      approach to dose escalation that is radiobiological in nature. The aim of this
      paper is to explain the rationale behind hypofractionated high-dose intensity
      modulated radiotherapy in patients with localized prostate cancer.

PMID- 23547395
TI  - Dynamic renal scintigraphy with 99mTc-DTPA for the assessment of renal function
      after therapy of acute lymphoblastic leukemia in children.
AB  - INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may lead to
      impairment of kidney function. The aim of the present study was to evaluate
      kidney function in children after treatment of ALL. We used our 99mTc-DTPA
      (diethylene triamine pentaacetic acid labeled with 99mTc) dynamic scintigraphy
      protocol. MATERIAL AND METHODS: The study group consisted of 48 ALL patients,
      aged 79-275 months, in complete remission (mean duration 51 months). Treatment
      was according to the guidelines of the Berlin Frankfurt Munster (BFM) BFM 86 and
      BFM 90 protocols in 36 (75%) and 12 (25%) children, respectively. Follow-up after
      treatment was up to 12 months in 10 (21%) children (group I), 12-60 months in 21
      (44%) children (group II), and more than 60 months in 17 (35%) children (group
      III). 99mTc-DTPA dynamic renal scintigraphy was done in all patients. The
      glomerular filtration rate (GFR) was determined according to Gates and the
      diuretic test was done after 18 minutes of the examination. RESULTS: The
      glomerular filtration rate at the end of the 5-year follow-up was less than 80
      mL/min/1.73 m2 (p < 0.002) in 3 (25%) children treated with the BFM 86 protocol.
      In the remaining 45 (94%) patients, GFR exceeded 80 mL/ min/1.73 m2. Normal
      renogram curves were obtained in 40 (83%) patients. Eight (17%) children had
      cumulative curves with normal clearance. This finding was interpreted as non
      obstructive uropathy. There was no statistical correlation between outflow
      disorders seen during dynamic scintigraphy, type of chemotherapy protocol, and
      assignment to risks group. CONCLUSIONS: 1. There was no clinically significant
      kidney function impairment in children after treatment of ALL. 2. Dynamic renal
      scintigraphy can be a valuable and non-invasive method for the assessment of
      kidney function in patients with a risk factor in the form of previous
      potentially nephrotoxic antitumor treatment.

PMID- 23547396
TI  - [Macrophage activation syndrome: report on three cases].
AB  - The macrophage activation syndrome (MAS) is a rare and potentially fatal disease.
      This syndrome is founded on congenital or acquired dysfunction of NK cells
      resulting in secondary activation and proliferation of macrophages with excessive
      cytokine production and organ infiltration. Causes of acquired MAS include viral
      infections (chiefly EBV and CMV), malignancies, and autoimmune diseases. The
      macrophage activation syndrome is usually associated with juvenile idiopathic
      arthritis and adult-onset Still's disease and rarely with rheumatoid arthritis,
      systemic lupus erythematosus, dermatomyositis, and systemic sclerosis. Fever,
      hepatosplenomegaly, lymphadenopathy, and bi- or pancytopenia in peripheral blood
      represent typical symptoms of MAS. Hyperferritinemia, hypertriglyceridemia,
      hypertransaminasemia, and hypofibrinogenemia are among the common laboratory
      findings. The macrophage activation syndrome is a life-threatening condition
      requiring aggressive therapy due to multiple organ dysfunction. Treatment also
      includes elimination of the triggering infection and high-dose
      glucocorticosteroids. Second-line therapy is based on cyclosporin, intravenous
      immunoglobulins, and etoposide. The present work focuses on diagnostic and
      therapeutic difficulties in three patients with the macrophage activation
      syndrome.

PMID- 23547397
TI  - [Inulin: a valuable nutritional component].
AB  - Inulin, a natural oligomer of fructose, is classified as a food component. It can
      be found in some plants and vegetables, i.e. chicory, Jerusalem artichoke,
      elecampane, and dandelion. Following ingestion, inulin reaches the lower part of
      the gastrointestinal tract where it is fermented increasing the bifidobacterial
      population of the colon. The growth of bifidobacteria regulates cholesterol
      concentration and absorption of minerals. Inulin added to food may prevent the
      spread of civilization diseases, like diabetes and obesity.

PMID- 23547398
TI  - School phobia in children with dyslexia.
AB  - PURPOSE: Dyslexic disorders are found in many children, affecting the emotional
      and social sphere and producing negative consequences for school functioning of
      the child. The aim of the present work was to determine the impact of the type of
      therapy on school phobia in dyslexic children. MATERIAL AND METHODS: 165 dyslexic
      children were examined using the questionnaire "Me and my school" developed by
      Elzbieta Skrzypek-Siwinska. The therapeutic experience of the children was taken
      into account and three groups were formed: 1) children with regular therapy; 2)
      children with occasional therapy; 3) children without therapy. RESULTS: Children
      with occasional therapy demonstrated higher levels of school phobia. These
      children exhibited a higher level of fear in situations when their knowledge was
      tested. Girls revealed a higher level of school phobia and knowledge testing
      fear, regardless of their therapeutic experience. CONCLUSIONS: The present study
      disclosed that the quality of therapy affects the emotional sphere of dyslexic
      children. Irregular therapy can produce serious consequences in the form of
      enhanced school phobia.

PMID- 23547399
TI  - The influence of lipid compounds on the content of fluorides in antlers and
      cranial bones of roe deer (Capreolus capreolus L.).
AB  - INTRODUCTION: Fluorine is a lipophilic element and for this reason lipids play a
      significant role in the accumulation and metabolism of fluorides in organs and
      bodily fluids. One of the places where interactions between fluorides and lipids
      can be observed are bones and antlers of deer. Even though the overall content of
      fluorides and lipid compounds in bones has repeatedly been analysed, we still
      know little about their interactions in antlers which are shed every year. The
      aim of this study was to determine the relation between the total content of
      total lipids and five most important fatty acids, linoleic acid (C 18:2 delta
      9.12), oleic acid (C 18:1 delta 9), palmitic acid (C 16:0), stearic acid (C
      18:0), and eicosadienoic acid (C 20:2 delta 11.14), and the content of fluorides
      in cranial bones and antlers of roe deer (Capreolus capreolus L.). MATERIAL AND
      METHODS: The content of fluorides in antlers and cranial bones of roe deer was
      measured with an ion-selective electrode, total lipids were determined with a
      spectrophotometric method, and fatty acids were identified with gas
      chromatography and an internal standard (heptadecanoic acid C 17:0). RESULTS AND
      CONCLUSIONS: The mean amount of fluorides in antlers and cranial bones was 0.0004
      mg/g (SD: 0.10718) and 0.0004 mg/g (SD: 0.14988), respectively. The mean content
      of lipids in antlers and cranial bones was 64.63736 mg/g (SD: 17.62648) and
      73.03208 mg/g (SD: 22.69000), respectively. In older animals, a tendency for
      fluorides to accumulate in antlers and frontal bones may be the reason why
      antlers appear less impressive, i.e. undergo involution.

PMID- 23547401
TI  - Endocrine conditions.

PMID- 23547400
TI  - [57th Congress of the Polish Association of Surgeons in September 6-9, 1995. A
      contribution to the history of the West Pomeranian Branch of the Polish
      Association of Surgeons].
AB  - The scientific and educational activity of the West Pomeranian Branch of the
      Polish Association of Surgeons during its 60 years of existence is presented on
      occasion of the 120 anniversary of the Polish Association of Surgeons. We present
      the profile of Professor Seweryn Wiechowski, the first head of the Department of
      Cardiosurgery in Szczecin, as well as his educational and research contributions
      and role he played in the development of general surgery and cardiosurgery in
      West Pomeranian. Professor Seweryn Wiechowski, acting as president of the Polish
      Association of Surgeons in 1993-1995 organized the 57th Congress of the Polish
      Association of Surgeons in September 6-9, 1995 held for the first time in
      Szczecin.

PMID- 23547402
TI  - Care of the newborn.

PMID- 23547403
TI  - Health care reform.

PMID- 23547404
TI  - Valvular heart disease.

PMID- 23547405
TI  - Gastrointestinal malignancies.

PMID- 23547406
TI  - Carotid intima-media thickness in type 2 diabetes mellitus.

PMID- 23547407
TI  - Genetics of lupus-untying the Gordian knot!

PMID- 23547408
TI  - Carotid intima-media thickness in type 2 diabetes mellitus patients with cardiac
      autonomic neuropathy.
AB  - INTRODUCTION: Cardiac autonomic neuropathy (CAN) is an important complication of
      type 2 diabetes mellitus (T2DM). Accelerated atherosclerosis is also common in
      T2DM. Carotid intima media thickness (CIMT) is a surrogate marker of
      atherosclerosis. We conducted a study to assess the CIMT in T2DM patients with
      CAN. METHODS: In 84 T2DM patients cardiac autonomic function was assessed by five
      clinical tests including: 1) heart rate variation during deep breathing, 2) hear
      rate response to standing, 3) Valsalva ratio, 4) postural fall in systolic blood
      pressure (BP) three minutes after standing, and 5) resting heart rate. CAN was
      defined as two or more positive tests out of five for cardiac autonomic function.
      CIMT was measured by two dimensional (2D) ultrasound. We also examined for
      presence of any atherosclerotic plaque over intima of carotid artery as well as
      within the carotid bulb. RESULTS: Thirty six (42.85 percent) out of 84 patients
      were detected to have CAN. CAN was significantly associated with duration of
      disease after its detection (P = 0.0253), high LDL cholesterol (P = 0.0418), low
      HDL cholesterol (P = 0.0001), fasting blood sugar (FBS) level (P = 0.0012) and
      CIMT (P = 0.0001) equal to or more than 69 mm. CONCLUSION: Increased CIMT equal
      to or more than 69 mm is associated with high occurrence of CAN in diabetic
      population. Duration of diabetes, abnormal lipid tests and FBS level
      significantly influence the development of CAN.

PMID- 23547409
TI  - Carotid artery intima media thickness in relation with atherosclerotic risk
      factors in patients with type 2 diabetes mellitus.
AB  - The present study was carried out to study the correlation between carotid artery
      intima media thickness (CIMT) with risk factors for atherosclerosis and
      atherosclerotic events in Type 2 Diabetes mellitus patients. The predictive value
      of CIMT as an indicator of early atherosclerosis was determined and the various
      atherosclerotic risk factors in type 2 diabetes mellitus were studied. Our study
      showed that CIMT was significantly higher in those type 2 diabetic patients who
      had atherosclerotic events than in those patients who had no atherosclerotic
      events. It was also found that waist hip ratio showed a significant positive
      correlation and independent association with CIMT emphasizing the emerging
      concept of central obesity. Duration of diabetes, urinary albumin excretion rate,
      hypertension and glycated hemoglobin had positive correlation with CIMT, but
      could not assume statistical significance. Age, smoking and dyslipidemia did not
      show any association with CIMT.

PMID- 23547410
TI  - Status of carotid intima-media thickness and associated risk factors in diabetic,
      prediabetic and non-diabetic acute stroke.
AB  - OBJECTIVE: Measure carotid intima-medial thickness (CIMT), its variability, risk
      factors, their correlation, in type 2 diabetic (DM), pre-diabetic (PDM) and non
      diabetic (NDM) acute strokes. METHODS: Twenty four DM and a matched population of
      14 patients each of PDM and NDM strokes were studied. Each group was compared as
      whole and by gender and stroke segregation. Study parameters were right and left
      CIMTs (CIMTR, CIMTL), insulin resistance (IR), age, BMI and lipids, correlations
      between CIMTs and CIMTs with risk markers. RESULTS: CIMTR was higher in DM and
      PDM compared to NDM, but CIMTLs did not differ. CIMTs were similar in genders and
      stroke types of each group. The IR was significantly high only in DM. Age and BMI
      correlations were predominantly positive and lipids variable except in PDM. Age
      and IR had better impacts on CIMTs in DM while BMI was poor. Females and infarcts
      had a more congruous CIMT increment in DM and PDM but male and haemorrhage in
      NDM. CONCLUSION: With similar levels of risk markers, their impacts on the CIMTs
      are highly variable at various levels of glycaemia. CIMTs were similar in the
      genders and stroke types of each group, irrespective of the glycemic status. The
      pre-diabetes group had distinct features.

PMID- 23547411
TI  - APO1/F AS promoter polymorphism in systemic lupus erythematosus (SLE):
      significance in clinical expression of the disease.
AB  - AIM: To identify APO1/FAS promoter (-670A/G) genotypes in Indian Systemic Lupus
      Erythematosus (SLE) patients and correlate with clinical presentation and serum
      FAS (sFAS) levels. MATERIAL AND METHODS: Seventy clinically diagnosed SLE
      patients and seventy healthy normals were included. SLE patients were classified
      according to the American College of Rheumatology (ACR) criteria. Disease
      severity was assessed by Systemic Lupus Erythematosus Disease Activity Index
      (SLEDAI). PCR-RF LP method was used to detect -670A/G APO1/FAS promoter
      polymorphisms. sFASLEvels were detected by ELISA. RESULTS: Out of 70 SLE
      patients, 35 were LN and remaining 35 were Non- LN. SLEDAI score was higher in LN
      patients (6-32) as against in Non-LN patients (6-23). Among SLE patients APO1/F
      AS promoter polymorphisms (A/G) showed highest frequency (54%), followed by A/A
      (31%) and G/G (15%) as compared to 60%, 10% and 30% respectively among normal
      population. Among SLE patients AA genotype showed statistically significant
      association against normals and 47% patients with A/A genotype showed severe
      clinical presentation (SLEDAI > 18). Mean sFASLEvels in SLE patients were 4771.5
      +/- 3280.9 pg/ml as compared to 1131.4 +/- 375.8 pg/ml in normals. Among SLE
      patients showing positivity for sFAS, 57.5% had A/G genotype, 27.5% had A/A
      genotype and 15% had G/G genotypes. CONCLUSION: This study showed a significant
      association of A/A genotype with severe clinical presentation in Indian SLE
      patients where sFAS might influence the severity and extent of organ involvement.
      Still a larger study is needed to support these findings.

PMID- 23547412
TI  - Localizationism to neuroplasticity---the evolution of metaphysical neuroscience.
AB  - Neuroplasticity (also referred to as brain plasticity, cortical plasticity or
      cortical re-mapping) is the changing of neurons, organization of their networks,
      and their function via new experiences. The brain consists of nerve cells or
      neurons and glial cells which are interconnected, and learning may happen through
      changing of the strength of the connections between neurons, by adding or
      removing connections, or by adding new cells. "Plasticity" relates to learning by
      adding or removing connections, or adding cells. Contrary to the traditional
      belief of neurolocalizationism, which states that each region of brain is
      dedicated for a particular type of activity, neuroplasticity has struggled a long
      way and has created a safe niche in the neuroscientific hall of honor. Salute to
      the neuroplasticians for their efforts to revolutionize the doctrine of neurology
      for the better understanding of the remarkable powers of brain. This article is a
      brief attempt to fathom the mysterious and scientific ways of neuroplasticity.

PMID- 23547413
TI  - Primary hyperparathyroidism.

PMID- 23547414
TI  - Poland syndrome with a rare association.
AB  - Poland syndrome is a rare congenital anomaly typically characterized by
      unilateral chest wall hypoplasia and ipsilateral hand abnormalities. Occasionally
      functionally debilitating, the disorder is mostly benign in nature with the
      severe deformities requiring surgical correction. A need to watch for possible
      malignant associations is also warranted. We present a case of a young female
      with the quintessential features of Poland syndrome with a relatively rare
      association of ipsilateral renal hypoplasia. We review the literature and discuss
      the possible renal complications that may arise and their management.

PMID- 23547415
TI  - Wilson's disease presenting with hypokalemia, hypoparathyroidism and renal
      failure.
AB  - Wilson's disease (WD) is not as rare as once believed, and has a wide range of
      presentations with equally wide range of age of onset. Sometimes the primary
      presentation might be unusual and may require a thorough investigation to avoid a
      misdiagnosis. Our case presented with uncontrolled seizures, severe hypokalemia,
      renal failure, and hypoparathyroidism. After being diagnosed as WD and treated
      for the same patient made a remarkable recovery.

PMID- 23547416
TI  - Autoimmune hepatitis--SLE overlap syndrome.
AB  - Autoimmune hepatitis also known as Lupoid hepatitis is an autoimmune liver
      disease characterized by the presence of autoantibodies including antinuclear
      antibodies (ANA) and hyper gammaglobulinemia. SLE can be associated with
      hepatitis, which is referred to as lupus hepatitis. It is important to
      distinguish these two entities, as the course of the disease is different in
      both. It has also been noted that these two entities can co-exist when it is
      referred to as Autoimmune hepatitis--SLE overlap syndrome. We are reporting a
      case of Autoimmune hepatitis--SLE overlap syndrome in a 30 years old lady.

PMID- 23547417
TI  - Unilateral lobar pulmonary edema.
AB  - INTRODUCTION: Pulmonary edema is usually bilateral, but unilateral lobar
      pulmonary edema can also be encountered in clinical practice. CLINICAL PICTURE:
      We describe a case of unilateral lobar pulmonary edema in a patient without known
      cardiac history. It was first presentation of underlying cardiac disease in our
      patient and was difficult to differentiate from pneumonia. CONCLUSION: Unilateral
      pulmonary edema can mimic as pneumonia. Clinician should be aware of differential
      diagnosis of pulmonary edema, otherwise it can lead to unnecessary investigation
      and delay in starting definitive treatment.

PMID- 23547418
TI  - Rare treatable limb girdle muscle disease.
AB  - We report two cases of Limb Girdle pattern of muscle weakness caused by
      hyperparathyroidism due to parathyroid adenoma. It can be easily missed as early
      symptoms are non specific but once diagnosed it is easily treatable and complete
      recovery occurs over a period of time.

PMID- 23547419
TI  - Helen Taussig.

PMID- 23547420
TI  - Reflections on the time of initiating ART in HIV-TB patients.

PMID- 23547421
TI  - Hepatic encephalopathy masking myxedema coma.

PMID- 23547422
TI  - The humor Prescription.

PMID- 23547423
TI  - Sole mate. Eleanor Leinen helps women step out in style.

PMID- 23547424
TI  - Variety--the spice of life.

PMID- 23547425
TI  - What's NEWsworthy about breastfeeding?

PMID- 23547426
TI  - New Medicare provisions to recognize and pay for core nursing services. ANA
      advocated including care coordination, transitional care in reimbursement
      policies.

PMID- 23547427
TI  - Cytologic diagnosis of spinal cord ependymoma in cerebrospinal fluid.
AB  - Ependymoma cells are known to rarely exfoliate into cerebrospinal fluid (CSF).
      However, the frequency of CSF involvement in patients with ependymoma is unclear,
      and to the author's knowledge the cytomorphologic features of tumour cells have
      not been well described to date. In this study, the CSF findings in a patient
      with ependymoma and the cytopathological features of this tumor are reported. The
      patient presented at the University Hospital of Heraklion, Crete, suffering from
      a chest to back pain. Computed tomography, scanning and magnetic resonance
      imaging (MRI) were performed and a mass of 3x2 cm in the thoracic aspect of the
      spinal cord was found. A sample of cerebrospinal fluid (CSF) was sent for
      cytologic examination and a diagnosis of ependymoma was made. A biopsy was
      performed and histology confirmed the cytologic diagnosis of ependymoma grade II
      (WHO). Exfoliated cells from ependymomas of spinal cord are rarely recognizable
      in CSF samples. Except in patients with myxopapillary tumours and anaplastic
      tumours, cytomorphologic features of ependymoma have been described only in case
      reports of intraoperative imprinting or fine needle aspiration biopsies (FNABs)
      and not in CSF cytology.

PMID- 23547428
TI  - Diffuse leptomeningeal glioneuronal tumours: clinico-pathological follow-up.
AB  - Glioneuronal tumours are a group of primary brain neoplasms of relatively recent
      acquisition in the World Health Organization (WHO) Classification of the Central
      Nervous System tumours. In diagnostic practice it is still possible to encounter
      glioneuronal tumours that cannot be placed into any of the well-defined WHO
      categories despite a growing list of entities. We have recently published four
      paediatric cases of diffuse leptomeningeal tumours that cannot be easily
      classified in the currently used CNS WHO classification, but which have
      histological and immunohistochemical criteria to be considered as glioneuronal
      tumours. The clinical, neuroradiological and pathological long-term follow-up of
      an unusual diffuse leptomeningeal glioneuronal tumour is presented herein.

PMID- 23547429
TI  - Molecular pathology of colorectal carcinoma. A systematic review centred on the
      new role of the pathologist.
AB  - Colorectal carcinoma (CRC) is the second most frequent malignant disease in
      developed countries. Many aetiological factors have been reported in CRC
      development including genetic or non-genetic (environmental) elements.
      Independently of these, three groups of alterations have been implicated: 1)
      chromosomal instability (CIN); 2) microsatellite instability (MSI); 3) CpG island
      methylator phenotype (CIMP). A different multistep association between these
      alterations contributes to determine three distinct developmental pathways:
      traditional, alternative and serrated. Each genotypic CRC assessment is
      associated with specific morphologic or clinical features. Pathologists have to
      consider the morphologic and clinical features of each CRC when study tumours
      with molecular tests. Chromatin remodelling is extremely dynamic and depends on
      several DNA-based processes, such as transcription, DNA repair and replication.
      The recent results with whole genome sequencing in a vast array of cancers have
      provided a catalogue of genetic lesions in chromatin modifiers that were
      previously unappreciated. It has revealed surprising facts about mutations in
      several SWI/ SNF complex members in many malignancies including CRC. The loss of
      INI1 expression is detected at a low rate in CRC and may be associated with
      differentiation grade and survival. Accumulating evidence suggests a critical
      role of the epithelial mesenchymal transition (EMT) in cancer progression. Some
      results support the existence of crosstalk between EMT and epigenetic
      modifications in the MSI-CRC group. We have summarized the role of
      genetic/epigenetic changes in the origin of the multiple CRC pathway, taking into
      account current knowledge of pathogenesis and feasibility of designing novel
      therapeutic approaches.

PMID- 23547430
TI  - High-grade primary peritoneal serous papillary carcinoma with a wide differential
      diagnosis: a diagnostic challenge.
AB  - Serous surface papillary carcinoma of the peritoneum is a rare malignant
      epithelial tumour that is histologically indistinguishable from high-grade serous
      papillary carcinoma of ovarian origin. We herein report a case of 66-year-old
      female with a history of breast carcinoma who presented with abdominal distension
      and shortness of breath. Imaging studies at the time of initial workup revealed
      multiple masses in abdominal cavity, and suspicion was high for metastatic
      carcinoma. The patient underwent exploratory laparotomy with total abdominal
      hysterectomy and bilateral salpingo-oophorectomy, partial colectomy, and
      omentectomy. Gross inspection of the omentum showed diffuse tumour caking, and
      frozen section evaluation of the omental nodules revealed adenocarcinoma with
      papillary features. Histological examination showed a high-grade papillary
      carcinoma with numerous psammoma bodies predominantly present within the omentum
      and peritoneum. Eventually, this case was determined to be a high-grade primary
      peritoneal serous papillary carcinoma involving the omentum, colon, and appendix,
      as well as the surfaces of the uterus, bilateral ovaries, and bilateral fallopian
      tubes. Knowledge of the primary organ of origin in cases of advanced papillary
      serous carcinomas is essential for both prognosis and staging, as well as for
      initiation of appropriate treatment. Close post-therapy follow up is required.

PMID- 23547431
TI  - Pancreatic heterotopia in the gallbladder neck associated with chronic
      cholecystitis.
AB  - The gallbladder is an unusual location of pancreatic heterotopia defined as the
      presence of pancreatic tissue lacking anatomical and vascular continuity with the
      main body of the gland. A 55-year-old previously healthy male patient presented
      with repeated attacks of right hypochondriac pain and vomiting. On physical
      examination, the right upper abdomen was tender to palpation with a positive
      Murphy's sign. Abdominal ultrasonographic examination showed multiple gallstones
      within a thin-walled gallbladder. Laparoscopic cholecystectomy was performed with
      uneventful recovery. Macroscopic examination of the surgical specimen revealed a
      yellowish intramural nodule measuring 7 mm close to the neck of the gallbladder.
      Histological examination revealed chronic cholecystitis and subserosal foci of
      heterotopic pancreas made up of exocrine acinar and ductal elements without islet
      cells corresponding to incomplete heterotopia. Heterotopic pancreas is usually
      detected as an incidental microscopic finding in a gallbladder specimen removed
      by cholecystectomy. Pre-operative diagnosis is difficult primarily due to its non
      specific clinical features.

PMID- 23547432
TI  - Ovarian fibromatous tumours of uncertain biological potential: study of three
      cases.
AB  - BACKGROUND: The classification of ovarian fibromatous tumours with high mitotic
      activity is controversial. CASES REPORT: The first case was an 18 x 17 x 10 cm
      left ovarian fibromatous tumour with 17 mitoses/10 HPF detected in a 44-year-old
      woman. The second case consisted of a 4 x 2.5 x 2 and a 2.5 x 2.5 x 2 cm
      fibrmatous tumours found, respectively, in the left and right ovaries of a 67
      year-old woman. The mitotic count varied from 4 to 6/10 HPF. CONCLUSIONS: Prat &
      Scully reported that mitotic activity was the most important factor in diagnosing
      fibrosarcomas, and that cellular pleomorphism was not reliable. Irving et al.
      suggested that cellular fibromatous neoplasms with bland nuclear features and
      mitotic count of > or = 4 MFs/10 HPFs should be considered mitotically-active
      cellular fibromas rather than fibrosarcomas. We propose the term 'fibromatous
      tumours of uncertain biological potential' when an average mitotic count of 4 or
      more per 10 HPFs are found and nuclear atypia and necrosis are absent.

PMID- 23547433
TI  - Subscapular elastofibrolipoma: a new variant type among elastofibromas or
      lipomas? A case report.
AB  - Elastofibroma is a rare soft tissue benign fibrous proliferation that
      characteristically occurs in periscapular soft tissues of the elderly,
      particularly in females, with typical morphological features consisting of an
      admixture of excessive collagen and abnormal elastic fibers displaying a beaded
      or globular appearance. Here we report an unusual, recently described
      histological variant with unclear origin, showing the presence of abundant mature
      fat tissue, named 'elastofibrolipoma', which could lead to confusion with other
      adipose and mesenchymal cell tumour proliferations. The issue as to whether
      elastofibrolipoma is reactive or neoplastic, variant of elastofibroma or lipoma,
      remains controversial. Differential diagnostic problems and histogenetic
      considerations are provided.

PMID- 23547434
TI  - A case of Stengel-Wolbach sclerosis: a half century after the last report.
AB  - Stengel-Wolbach sclerosis is a rare form of granulomatosis of the lymphoid
      tissue, with largely predominant involvement of the spleen. Firstly described by
      Wolbach in 1910, it has disappeared from the literature from the beginning of the
      last century. Herein, we describe the case of a 29-year-old female with
      splenomegaly due to multiple nodular lesions. On the basis of morphological and
      molecular biology findings, a diagnosis of Stengel-Wolbach sclerosis of unknown
      aetiology was made. The presentation of this case may reopen the discussion on
      this enigmatic entity.

PMID- 23547435
TI  - Common fractures.

PMID- 23547436
TI  - Better health begins with better understanding. Industry experts discuss disease
      management solutions.

PMID- 23547437
TI  - Lessons learned. How to smooth your EHR implementation.

PMID- 23547438
TI  - This isn't my information! The impact of accurate identity management on patient
      safety.

PMID- 23547439
TI  - Turning CIOs into chief interoperability officers. New survey stresses the need
      for health IT collaboration.

PMID- 23547440
TI  - Integrating IT for next-gen EMRs. Unifying disparate systems and content with the
      EMR helps providers operate more efficiently.

PMID- 23547441
TI  - Empowering patients through advanced EMR use. The role of patient education and
      health literacy in patient portals.

PMID- 23547442
TI  - The Nevada solution. Expected benefits also translate into potential challenges
      for health insurance exchanges.

PMID- 23547443
TI  - Considering telehealth? The right network infrastructure is critical.

PMID- 23547444
TI  - Saving lives at the speed of light. The private fiber network has been shown to
      dramatically reduce the time required to perform virtually any healthcare
      function.

PMID- 23547445
TI  - Examining Medicare readmissions. Strategies to mitigate potential revenue hits.

PMID- 23547446
TI  - How to implement RAC tracking. Evaluating, implementing and getting every dollar
      out of RAC audit management software.

PMID- 23547447
TI  - Meaningful, meaningful use. Moving beyond implementation to strategy and analysis
      to improve clinical processes.

PMID- 23547448
TI  - [Significance of the double mutations of C1673T/C1799G in HBV C promoter].
AB  - OBJECTIVE: To explore the biological and clinical significance of the double
      mutations of C1673T/C1799G in HBV C promoter (CP). METHODS: Totally 136 patients
      were enrolled, including 25 asymptomatic carriers (AsC), 38 patients with chronic
      hepatitis B (CHB), 24 patients with chronic severe hepatitis B (CSHB), 36 cases
      with liver cirrhosis (LC) and 13 cases with hepatocellular carcinoma (HCC). HBV
      subgenotypes and mutations in CP of all samples were determined by nested-PCR and
      direct nucleotide sequence analysis. The C to T mutation at nucleotide 1673 and C
      to G at nucleotide 1799 were analyzed in different subgenotypes, and the
      relationships of C1673T/C1799G double mutations with HBV replication, the
      expression of HBeAg, and with the severity of liver disease after chronic HBV
      infection were studied. RESULTS: Of the 136 patients, 110 were subgenotype Ba, 1
      was Bj, 7 were C1, and 18 were C2. C1673T/C1799G double mutations in Ba were
      determined in 106 (96. 4%) samples, which was significantly higher than in C1
      (14.3%) and C2 (12.5%) subgenotype (P < 0.0001). In contrast to non-mutation
      group, HBV DNA content in mutation group had no significant difference (P >
      0.05). The prevalence of the mutation was lower in HBeAg positive patients
      (71.4%) than in HBeAg negative patients (87.5%) (P < 0.05). The frequencies of
      the double mutations were not significantly different among ASC, CHB, CSHB, LC
      and HCC groups (P > 0.05). CONCLUSION: In Ba subgenotype, double mutations of
      C1673T/C1799G is much popular than in C1 and C2; the mutation has no effect on
      HBV replication, and may not be associated with the outcome of chronic HBV
      infection.

PMID- 23547449
TI  - [A correlation analysis of HBV-DNA load levels between in perinatal mother's
      serum and neonatal cord blood].
AB  - OBJECTIVE: To investigate the correlations of hepatitis B virus markers and
      hepatitis B virus -DNA vectors in blood between women in perinatal period and
      cord blood, and to assess the risk of HBV infections status in pregnant women to
      intrauterine fetal infective. METHODS: We selected 612 pregnant women who decided
      to delivery in hospital, in compliance with the principles of informed consent.
      According the difference of hepatitis virus serological markers existing in
      pregnant women, samples were divided into six groups. We used enzyme-linked
      immunosorbent assay to detect hepatitis virus serological markers, existing in
      serum of mother and cord blood. Real-time fluorescence quantitative PCR was
      supplied to test HBV-DNA load levels in these two kinds of biological specimen.
      RESULTS: In group A, hepatitis B virus "big 3 positives" or 1,3 positive 149
      lying-in woman examples, two positive rates of HBV-DNA about pregnant women and
      cord blood are 99.33% and 32.21%; in group B, positive rates of HBV-DNA in two
      kinds of specimen are 20.00% and 3.08%; in group C and D, two positive rates are
      and the average contents of HBV-DNA, the results as mentioned in each group
      respectively are 65.52%, 12.07% and 13.56%, 1.69% respectively. Control group is
      group E, 86 lying-in woman examples and the detecting results orderly are 1.16%,
      0. There was a significant difference in positive rate of HBV-DNA in cord blood
      between group A and group B subgroups (chi2 = 54.09, P < 0.01). There is
      significant positive correlation between HBV-DNA vectors existing in mother's
      serum and the positive rate of HBV-DNA in cord blood. Hepatitis B virus the
      mother blood " big 3 positives " is the umbilicus blood HBV-DNA 6345 times that
      carries quantity in average. CONCLUSION: (1) During the perinatal period, along
      with the HBV-DNA load levels arising of pregnant women, the risk of HBV
      infections status in pregnant women to intrauterine fetal infective increased.
      (2) Suggested to develop the compound pattern human hepatitis B immunoglobulin:
      Increase the composition of efficient price HBeAb-can be combinated HBeAg, HBsAb
      can be combinated HBsAg, strengthen the hinderance and break hepatitis B virus
      disseminate. (3) Our government should strengthen the propaganda of hepatitis B
      virus education. Establish and perfect to surround and produce the system of
      health protection.

PMID- 23547450
TI  - [Analysis of relationship of HBV PreS1 antigen, anti-HBc IgM, DNA load and
      genotypes in hepatitis B patients].
AB  - OBJECTIVE: To explore the relationship of HBV PreS1 antigen, anti-HBc IgM, DNA
      load and genotypes, and the significance for clinical diagnosis and prognostic.
      METHODS: Enzyme linked immune-sorbent assay was used to test the HBV serum
      markers of HB patients; HBV-DNA copies was detected by time fluorescence
      quantitative PCR; using nested PCR to amplify the S fragment of HBV genome, then
      sequence and make blast with HBV standard sequences to ascertain genotypes. Make
      comprehensive analysis of these indexes. RESULTS: 355 serum specimens of acute or
      chronic HB patients were collected. The positive rates of HBV PreS1-Ag and HBV
      DNA in model I (positive for HBeAg) were 80.2% and 73.7% respectively, which both
      higher than other models. The abnormal rate of ALT and AST were higher in PreS1
      Ag positive group than negative, as well as in anti-HBc IgM positive group. There
      are 4 samples is genotype B (2.9%), 76 genotype C (55.9%) and 56 genotype D
      (41.2%). Positive rate of HBeAg and HBV-DNA of genotype C samples were both
      higher than which of genotype B and D. CONCLUSION: PreS1-Ag and Anti-HBe-IgM
      indexes are of great value to viral hepatitis B early diagnosis, HBV replication
      surveillance and prognostic evaluation; the major HBV genotypes in Henan province
      are C and D, and the positive rate of HBeAg and HBV-DNA were both higher in
      genotype C HBV infection population than genotype B and D.

PMID- 23547451
TI  - [MicroRNA differential expression profiles in DC after the stimulation of HBsAg].
AB  - OBJECTIVE: To establish the differential expression profiles for exploring new
      immune mechanism of hepatitis B virus infection. METHODS: DCs were separated from
      the bone marrow of healthy mouse and cultured in vitro. Then DCs were stimulated
      with HBsAg, LPS, TNF-alpha, respectively. Twenty-four hours later, the total RNA
      of cell was extracted. cDNA microarray was used to compare the differential
      expression of RNA. The significant differential expression of miRNA after the
      stimulation of HBsAg was chosen. Subsequently, target genes of the significant
      differential miRNA were forecasted by using computer software. RESULTS: There
      were 30 miRNAs whose significant differential expressions were beyond two times
      after the stimulation of HBsAg. Among them, 16 miRNAs expressions were increased
      and 14 miRNAs expressions were decreased. There was significant difference in
      differential expression of miRNA among the 3 different stimulations. The selected
      target genes included relevant elements of signal pathway of DC. CONCLUSION: The
      alteration of expression profiles of miRNA was specific after DC was stimulated
      by HBsAg. The selected target genes further demonstrated that miRNA could play
      important roles in the immune mechanism of HBV infection.

PMID- 23547452
TI  - [Effect of gene optimization on the expression and purification of HDV small
      antigen produced by genetic engineering].
AB  - OBJECTIVE: To study the effect of gene optimization on the expression and
      purification of HDV small antigen produced by genetic engineering. METHODS: Based
      on the colon preference of E. coli, the HDV small antigen original gene from
      GenBank was optimized. Both the original gene and the optimized gene expressed in
      prokaryotic cells, SDS-PAGE was made to analyze the protein expression yield and
      to decide which protein expression style was more proportion than the other.
      Furthermore, two antigens were purified by chromatography in order to compare the
      purity by SDS-PAGE and Image Lab software. RESULTS: SDS-PAGE indicated that the
      molecular weight of target proteins from two groups were the same as we expected.
      Gene optimization resulted in the higher yield and it could make the product more
      soluble. After chromatography, the purity of target protein from optimized gene
      was up to 96.3%, obviously purer than that from original gene. CONCLUSION: Gene
      optimization could increase the protein expression yield and solubility of
      genetic engineering HDV small antigen. In addition, the product from the
      optimized gene group was easier to be purified for diagnosis usage.

PMID- 23547453
TI  - [Isolation and sequence analysis on virus of HFMD with encephalitis in Yantal
      city].
AB  - OBJECTIVE: To learn about the pathogen spectrum and genetic characterization of
      HFMD with encephalitis in Yantai city. METHODS: Stool samples and cerebrospinal
      fluids (CSF) collected from HFMD with encephalitis cases in Yantai. Virus were
      isolated from stool samples and identified by fluorescence reverse transcription
      polymerase chain reaction. The VPl region was amplified and sequenced from
      positive specimens. Genetic characterization was identified by sequence analysis.
      RESULTS: Getting 3 virus strains from 10 stool specimens and all of them belong
      to EV71. The nucleotide and amino acid homogeneity with the representative
      isolates of C4a were 98%-99% and 98.90%-99.45% respectively. CONCLUSION: The
      pathogen of HFMD with encephalitis in Yantai city were mainly EV71 wich belong to
      subgenogroup C4 cluster C4a.

PMID- 23547454
TI  - [Detection the pathogens and analysis the clinical characteristics in children
      with hand, foot and mouth disease in Shanghai during 2009-2011].
AB  - OBJECTIVE: To investigate the epidemic characteristics of etiological agents and
      analyze the clinic differences in children with hand, foot and mouth diseases in
      Shanghai. METHODS: Collection 551 specimens including vesicle fluid, stool and
      throat swabs to detect the pathogens. The positive rates were tested by RT-PCR
      assay with Enterovirus consensus primer and specific primer for Enterovirus 71
      (EV71) and Coxsackie A16 (CoxA16), respectively. RESULTS: Out of 357 patients,
      the overall positive rate was 79.7%. CoxA16 infection was mainly popular in 2009,
      EV71 was mainly popular in 2011. The epidemic characteristics of enterovirus
      infection within 2009-2011 had significant differences (P = 0.005). The positive
      rate of vesicle fluid was highest. The concurrent rate of fever and tendency to
      be frightened had significant differences in three patients' groups. The count of
      the peripheral white blood cells and the ratio of the neutrophil in the patients
      with EV71 infection was higher than that in the patients with CoxA16 or PE
      infection. CONCLUSION: HFMD showed alternant epidemic characteristics at
      different times of enterovirus infection in Shanghai. Analyzing the differences
      of clinic characteristic of EV71 and CoxA16 infection is helpful to prevent and
      control EV71 infection.

PMID- 23547455
TI  - [Genotype of hantavirus in Zhejiang province].
AB  - OBJECTIVE: To identify the genotype and clades of hantavirus (HV) in Zhejiang
      province. METHODS: The partial S and M segment of the HV in Zhejiang province
      were amplified with RT-PCR using genotype-specific primers, and then were
      sequenced and compared with other known hantaviruses. RESULTS: The genotype of 11
      strains were HTNV and other 7 strains were SEOV by homology and phylogenesis
      analysis, yet the clade distribution was significantly different among foci of
      Zhejiang with 5 clades of HTNV and 3 clades of SEOV. There also existed special
      clade of HTNV named ZNB-1, ZNB-2, A3 and of SEOV named Gou3, ZJ5. The homology of
      M segments of ZNB-1 and ZNB-2 with other HTNV clades were 69.7%-74.0% except
      Nc167, A3 with other HTNV clades were 73.6%-76.3% except B78. CONCLUSION:
      Zhejiang province is co-circulating with HTN and SEO. Say the least of the clades
      are 5 of HTNV and 3 of SEOV and there also existed special clade of HTNV and
      SEOV.

PMID- 23547456
TI  - [The relationship between two kinds of human herpesviruses and experimental
      gingivitis].
AB  - OBJECTIVE: To investigate human cytomegalovirus (HCMV) and Epstein-Barr virus
      type 1 (EBV-1) in GCF and saliva during experimental gingivitis in Chinese young
      subjects and to evaluate the effect of the virus in the initial stage of gingival
      inflammation. METHODS: GCF of 14 and 45 and saliva without stimulating in 11
      Chinese young males with healthy gingiva were collected at baseline (day 0), day
      7, 14 and 21 after stopping oral hygiene and day7 after reestablishing oral
      hygiene (day 28). DNA of HCMV and EBV-1 were detected by nested-polymerase chain
      reaction (n-PCR) at the times mentioned above. RESULTS: HCMV was detected in GCF
      of 4 subjects at baseline, 4 subjects at day 7, 3 subjects at day 14 and 2
      subjects at day 21 while the subjects were different. At day 28 HCMV could not be
      detected. EBV-1 was not detectable in GCF during the experimental gingivitis.
      HCMV was detected in saliva in 4 subjects and EBV-1 was in 3 subjects. And there
      is no relationship between the detection of the herpesviruses and the clinical
      parameters as well. CONCLUSION: We suggest that HCMV and EBV-1 are not the
      important factors during the initial stage of gingival inflammation.

PMID- 23547457
TI  - [Characteristic of nuclear antigen 1 gene and latent membrane protein 1 gene of
      Epstein-Barr virus in primary EBV infection in children in Beijing area in 2005
      2010].
AB  - OBJECTIVE: To analyze the characteristic of nuclear antigen 1 gene and latent
      membrane protein 1 gene of Epstein-Barr virus in primary EBV infection in
      children in Beijing area in 2005-2012. METHODS: Polymerase chain reaction (PCR)
      was used to amplify the EBNA-3C, EBNA1 and LMP1 genes. The amplified products
      were sequenced directly and the sequences were analyzed by BioEdit 7. 0. 9 and
      MEGA 4. 0. 2. RESULTS: Type A EBV was detected in 98% samples. Nucleotide
      sequence analysis of the carboxy-terminal region of EBNA1 showed that Vvvl was
      deteted in 98% samples. DNA sequence analysis of LMP1 C-terminus indicated that
      China 1 was 90% in this study. There were no significant differences in the
      frequency of Vvv1 and China 1 between the IM and HLH samples (P = 1.00). Linkage
      analysis of EBV types, EBNA1 and LMP1 variants indicated that 90% of EBV type A
      was associated with EBNA1-Vvv1 variant and LMP1-China 1 variant in 40 cases. Full
      length of LMP1 gene was successfully amplified in 35 cases. Four Chinese groups
      (CG1-4) were identified. The percentage of CG1-CG4 were 85%, 6%, 6% and 3%,
      respectively. CONCLUSION: EBV type A is predominant in primary EBV infection in
      children in Beijing Area. EBNA1-Vvv1 and LMP1-China 1 variants were predominant
      genotypes in this area. There is a high linkage between EBNA1-Vvv1 variant and
      LMP1-China 1 variant. Four Chinese groups (CG1-4) were identified according to
      the full length of LMP1 gene and CG1 was the most prevalent.

PMID- 23547458
TI  - [The analysis of human papillomavirus infection in lip squamous cell carcinoma
      patients].
AB  - OBJECTIVE: To analyze the infection of human papillomavirus in lip squamous cell
      carcinoma patients. METHODS: The pathological samples of 9 clinical diagnosed lip
      cancer patients were collected. Lunimex and PCR techniques were used to detect
      the HPV gene infection and immunohistochemistry method was used to analyze the
      HPV protein expression in the samples. RESULTS: In the 9 cases, 1 was positive
      for HPV16 gene and 7 were positive for HPV16/18 E6 protein expression. The total
      positive rate was about 8/9. CONCLUSION: The high HPV infection rate in lip
      cancer patients in the study indicated indirectly that the importance of the
      direct contact to the infection of HPV what was the basis for pathogenesis of the
      lip squamous cell carcinoma.

PMID- 23547459
TI  - [Comparison of prediction performance of PAHs carcinogenicity between a BALB/c
      E6E7 cell transformation assay and a BALB/c 3T3 cell transformation assay].
AB  - OBJECTIVE: To predict the carcinogenicity of polycyclic aromatic hydrocarbons
      (PAHs) by cell transformation assay using BALB/c 3T3 cells and HPV16-E6E7
      transfected BALB/c 3T3 cells (BALB/c-E6E7 cells). METHODS: The cell
      transformation assays induced by PAHs using BALB-E6E7 cells and BALB/c 3T3 cells.
      RESULTS: The initiating and promoting activities of PAHs examined in a BALB-E6E7
      cell transformation assay were similar to in a BALB/c 3T3 cell transformation
      assay, which was up to the standard of agents classified by the IARC. There were
      much more transformed foci appeared and much shorter time consumed to accomplish
      phenotypic alterations in the BALB/c-E6E7 cell transformation assay than in the
      BALB/c 3T3 cell transformation assay. The BALB/c-E6E7 cell transformation assay
      was superior to the BALB/c 3T3 cell transformation assay in cost and labor
      performance, the sensitivity of transformation response. CONCLUSION: The BALB/c
      E6E7 cell transformation assay, with a satisfied prediction performance of
      initiating activity and promoting activity, would improve the overall process of
      safety and risk assessment of carcinogenicity.

PMID- 23547460
TI  - [Small interfering RNA targeting to hepatitis B virus X gene and 5-aza-2'
      deoxycytidineon inhibited growth of the subcutaneous implanted tumor of
      hepatocellular carcinoma in nude mice].
AB  - OBJECTIVE: To investigate the anti-tumor effect of small interfering RNA
      targeting to HBV X gene (X-siRNA) and 5-aza-2'-deoxycytidine (5-aza-dC) on HBV
      related hepatocellular carcinoma. METHODS: X-siRNA and control siRNA were
      synthesized. HepG2/GFP-HBx cells were treated with X-siRNA, and the levels of HBV
      X mRNA were detected by semi-quantitative reverse transcription polymerase chain
      reaction (RT-PCR). Nude mice were inoculated with HepG2/GFP and HepG2/GFP-HBx
      cells subcutaneous respectively to establish implant models of hepatocellular
      carcinoma, and were treated with X-siRNA, 5-aza-dC alone or in combination, and
      tumor growth was observed. The methylation of p16 gene promoter was detected by
      methylation specific polymerase chain reaction (MSP). RESULTS: RT-PCR showed the
      expression of HBV X mRNA in HepG2/GFP-HBx cells was inhibited markedly by X
      siRNA. The nude mice experiment showed that the gross tumor volume was much
      bigger in HepG2/GFP-HBx group than that in HepG2/GFP group (P < 0.05). The growth
      of palpable tumors in X-siRNA or 5-aza-dC treatment group notably decreased (P <
      0.05). MSP analysis showed that p16 gene methylation was observed in HepG2/ GFP
      HBx-caused palpable tumors, while no methylation was detected in HepG2/GFP group.
      However, after treatment with X-siRNA or 5-aza-dC, p16 gene methylation reduced.
      CONCLUSIONS: HBV X-siRNA and methylation inhibitor can inhibit the growth of
      hepatoma cells via reversing p16 methylation.

PMID- 23547461
TI  - [The protective effect of N-acetylcysteine magnesium against liver cirrhosis with
      portal hypertension in rat].
AB  - OBJECTIVE: To study the effects of acetylcysteine magnesium on the vasoactive
      substances and hepatic fibrosis indexes in liver cirrhosis and portal
      hypertension of rats. METHODS: The rat liver cirrhosis model was made with 12
      microg/kg dimethylnitrosamines. Then acetylcysteine magnesium was injected
      respectively with 25, 50, and 100 mg x kg(-1) dose daily into abdominal cavity.
      After 8 weeks treatment, pathological section, TGF-beta1, NO, TNOS and iNOS of
      hepatic tissue were detected to assess the effect of acetylcysteine magnesium
      against cirrhosis portal hypertension. RESULTS: After the DMNA modeling was
      completed, the HE and Sweet reticulocyte staining of liver pathological section
      showed that cirrhosis of the liver was in the III-IV phase, the infiltration of
      lymphocytes and formation of pseudolobuli in liver were alleviated in three
      acetylcysteine magnesium treatment groups (low, medium, and high dose), and the
      degree of liver fiber sclerosis in three groups was significantly lower than
      control group. Compared with control group, TGF-beta1, NO, TNOS and iNOS were
      significantly reduced in all treatment groups (P < 0.05). CONCLUSION:
      Acetylcysteine magnesium is probably a distinctive antioxidant which can remove
      various free radical in body and modulate ligand-dependent signal transduction
      and the growth of cell. It also have protection in the liver cirrhosis and portal
      hypertension of rats induced by dimethylnitrosamine.

PMID- 23547462
TI  - [Mutant D178N prion protein converts spontaneously in RT-QuIC assay].
AB  - OBJECTIVE: To study the conversion of mutant D178N prion protein in RT-QuIC
      assay. METHODS: The D178N mutant prion PRNP was generated by the method of single
      site mutation. The mutant PRNP gene was inserted into plasmids of pET24. The full
      and N-truncated recombinant human prion proteins were expressed and purified. The
      fibril formations of these proteins were real-time monitored by the method of RT
      QuIC. The ability to resist proteinase K (PK) of these fibrils was analyzed.
      RESULTS: We succeed to construct human PrP-D178N plamids. The N-truncated human
      prion protein with D178N (PrP90-231-D178N) can convert spontaneously in RT-QuIC,
      while full length of human prion D178N protein (PrP23-231-D178N) fails to convert
      spontaneously. The spontaneously generated fibril has been domenstrated it is
      partily PK-resistant. CONCLUSION: The N-terminal of prion protein (23-90) plays
      an important role for the D178N mutant protein spontaneously conversion, which
      provide the clues for study the pathogenesis of genetic CJD.

PMID- 23547463
TI  - [Three-year efficacy and side effect of adefovir dipivoxil for the treatment of
      the old patients with chronic hepatitis B virus infection].
AB  - OBJECTIVE: To investigate 3-year antiviral efficacy and side effect of adefovir
      dipivoxil (ADV) on the old patients with hepatitis B chronic infection. METHODS:
      31 HBeAg-negative chronic hepatitis B virus infected old patients (include 8
      patients with chronic hepatitis B and 23 patients with liver cirrhosis) with
      serum HBV DNA levels > 1000 copies/ml, and ALT > 2 times the upper limit of
      normal, without company with other liver diseases, cancer, renal dysfunction, and
      autoimmune disease. All the patients were treated with ADV orally (10 mg once
      daily) for 36 months. HBV DNA and biochemical and blood routine indexes were
      checked after treated. RESULT: Serum total bilirubin, direct bilirubin, alamine
      aminotransferase, aspartate aminotransferase and load of HBV DNA decrease
      significantly after therapy (P < 0. 001). Other biochemical indexs and blood
      routine are no significant changes (P > 0.05). CONCLUSION: The way to treat with
      ADV is safe and effective for old patients with chronic hepatitis B virus
      infection.

PMID- 23547464
TI  - [The investigation of hepatitis D virus infection situation in the human with
      HBsAg in Foshan of Guangdong province].
AB  - OBJECTIVE: To investigate the seroprevalence of hepatitis D virus in Foshan of
      Guangdong province, to provide the data for the study about it in China. METHODS:
      ELISA kits from two different companies were used for detecting anti-HDV IgG of
      all the serum samples, and then RT-PCR was carried out about the selected serum
      to ensure the results. All the serum samples were collected in 2011 in The First
      People's Hospital of Foshan. RESULTS: The results from two ELISA kits and RT-PCR
      were identical. Eight samples were positive. CONCLUSIONS: The seroprevalence rate
      of HDV in Foshan is higher than that in China. It has no statistically
      significant difference between female and male. Morever, the older with HBsAg are
      susceptible to HDV.

PMID- 23547465
TI  - [Applicability of a sensitive duplex real-time PCR assay for identifying
      B/Yamagata and B/Victoria lineages of influenza virus].
AB  - OBJECTIVE: To develop a novel sensitive duplex real-time PCR assay for accurately
      identifying B/Yamagata and B/Victoria lineages of influenza virus type B.
      METHODS: 50 HA (hemagglutinin) gene sequences coding for B/Yamagata and
      B/Victoria lineage, respectively, were randomly downloaded for GenBank and
      analyzed by software MEGA. Primers and probes specific for HA gene of B/Yamagata
      and B/Victoria lineages were designed by Primer Primer and then applied in the
      duplex real-time RT-PCR method that was followed developed. Influenza virus B
      type and A type isolated in our laboratory and typing-confirmed by HAI method
      were used as reference strains to determine the specificity of this assay and the
      sensitivity of the duplex amplification was evaluated by viral load testing in
      terms of in vitro transcribed RNA copy number. RESULTS: In 2006-2010, 793
      influenza virus type B strains were isolated from 17 765 throat swab samples,
      among which 152 strains were differentiated as By lineage and 641 as Bv lineage
      by this assay. These results was agreement with that determined by HAI assay.
      This developed assay allows to accurately identify approximately 10(2)
      copies/microl for Bv and By lineage virus with intra- and inter-coefficient of
      variation (CV) < 3.5% and nearly 100% specificity. CONCLUSIONS: This method
      provides sensitive and robust tool for routine diagnosis and on-time
      epidemiological examination of influenza virus, which could be applied in
      influenza surveillance laboratories for rapid molecular diagnosis.

PMID- 23547466
TI  - [Simultaneous detection of human parainfluenza viruses 1, 2, 3 by multiplex real
      time reverse transcription-polymerase chain reaction with LNA probes].
AB  - OBJECTIVE: Human parainfluenza virus (HPIV) types 1, 2 and 3 are major viral
      pathogens responsible for upper and lower respiratory tract infections. In this
      study, a real-time RT-PCR was developed using multiplex primers-probe (HPIV-1, 2,
      3) for the simultaneous detection of both HPIV1, HPIV2 and HPIV3 genomes.
      METHODS: Optimal primers and probes were designed using specialized software. The
      conditions for multiplex real-time RT-PCR had been optimized. The synthesis of
      RNA standards of HPIV1, 2, 3 were used a T7 RNA polymerase. Check the specificity
      sensitivities and stability of one step RT-PCR assay. RESULTS: Obtained in a 10
      fold dilution series assay demonstrate a high sensitivity of the assay with a
      lowest detection limit of 10 copies for HPIV1, 100 copies for HPIV2 and 100
      copies for HPIV3. CONCLUSION: The assays demonstrates an improved sensitivity and
      scope of detecting HPIV1, 2, 3 viruses relative to routine antigen detection
      assays while the quantitative utility may facilitate investigation of the pre
      diagnosis and respiratory virus pathogenesis.

PMID- 23547468
TI  - [Polypeptide toxin from sea anemone inhibiting proton-sensitive channel ASIC3].
AB  - Polypeptide toxin pi-AnmTX Hcr 1b-1 with a molecular weight 4537 Da was isolated
      from the whole body extract of sea anemone by a multistage liquid chromatography.
      The BLAST search algorithm revealed homology of the novel toxin amino acid
      sequence to the group of the known sea anemone toxins including BDS and APETx
      with similarity less then 50%. The toxin pi-AnmTX Hcr 1b-1 inhibited the
      amplitude of the fast component of integral ASIC3 current in electrophysiological
      studies on receptors expressed in Xenopus laevis oocytes. The calculated IC50
      value was 5.5 +/- 1.0 microM. Among the known polypeptide toxins interacted with
      ASICs channels, the micro-AnmTX Hcr 1b-1 toxin is the least potent inhibitor that
      in our opinion correlates with a small amount of charged amino acid residues in
      its structure.

PMID- 23547467
TI  - [Perspectives of application of recombinant diphtheria toxin derivatives].
AB  - Diphtheria toxin (DT) is a unique bacterial protein, which selectively kills
      certain cell populations due to strict functional specialization of domains that
      allows using this toxin in protein engineering for constructing recombinant
      derivatives with defined properties. The article covers structural and functional
      features of DT molecule, both fundamental and practical aspects of recombinant DT
      derivatives' applications in different fields. In particular, applications of
      recombinant DT derivatives as unique instruments for fundamental research of cell
      receptors' functions, mechanism of DT action and participation of different cell
      populations in biological processes are presented. Perspectives of recombinant DT
      derivatives practical applications for the development of vaccines, cytotoxins,
      HB-EGF blockers, diagnostic test-systems, serotherapeutic medications and
      constructions for drug delivery have been discussed. This review reflects recent
      advances and current problems in using recombinant DT derivatives for treatment
      and prophylaxis of oncologic, autoimmune, infectious and others diseases.

PMID- 23547469
TI  - [Peptide fragments of chemokine domain of fractalkine: effect on human monocyte
      migration].
AB  - Leukocyte chemotaxis to the area of tissue damage is mediated by chemokines.
      According to the primary structure, chemokines are divided into four families,
      fractalkine (CX3CL1) is the only one member of CX3C family and the only membrane
      bound chemokine. Fractalkine molecule includes the extracellular N-terminal
      chemokine domain, mucin-like rod, the transmembrane and the intracellular
      domains. In membrane-bound state fractalkine has the properties of an adhesion
      molecule. Chemokine domain of fractalkine (CDF) is released from cell membrane by
      proteolysis, and this soluble form acts as a chemoattractant for leukocytes
      expressing fractalkine receptor CX3CR1. Fractalkine is involved in development of
      a number of pathological processes caused by inflammation, and therefore a search
      for fractalkine inhibitors is very important. For this purpose we identified
      several antigenic determinants--the fragments of CDF, and the following peptides
      were synthesized--P41-52 H-Leu-Glu-Thr-Arg-Gln-His-Arg-Leu-Phe-Cys-Ala-Asp-NH2,
      P53-60 H-Pro-Lys-Glu-Gln-Trp-Val-Lys-Asp-NH2 and P60-71 H-Asp-Ala-Met-Gln-His-Leu
      Asp-Arg-Gln-Ala-Ala-Ala-NH2. The peptide effects on adhesion and migration of
      human peripheral blood monocytes expressing fractalkine receptors were
      investigated. In the presence of CDF and P41-52 we observed the increased
      adhesion and migration of monocytes compared with spontaneous values. Peptides
      P53-60 and P60-71 significantly inhibited monocyte adhesion and migration
      stimulated by CDF. Since the chemotactic activity of chemokines was shown to be
      dependent on their binding to glycosaminoglycans of the cell surface and
      extracellular matrix, the effect ofpeptides on the interaction of CDF with
      heparin was analyzed by ELISA. Peptide P41-52 competed with CDF for heparin
      binding, while peptides P53-60 and P60-71 had no significant activity.

PMID- 23547470
TI  - [Anti-peptide antibodies specifically recognize the L1 protein of human papilloma
      virus type 31].
AB  - Antibodies that specifically recognize the capsid protein (L1) of human
      papillomavirus (HPV) are an important tool necessary for designing vaccines
      against HPV infection. In this work, we have predicted and synthesized peptide
      fragments mimicking B cell epitopes of L1 HPV type 31 (sequences 49-65, 131-145,
      172-189, 349-362 and 402-414), and conjugated their to KLH and BSA to generate
      the L1-31-specific anti-peptide antibodies in mice. Variants of recombinant L1
      31, including full-size and mutants with C-terminal single amino acid changes and
      deletions and full-size L1-16 were produced in the yeast using monitoring with L1
      HPV16-specific monoclonal antibody. Testing of anti-peptide antisera in ELISA
      showed that antibodies to peptides 49-65 and 172-189 were capable to recognize
      specifically L1-31 protein, but not L1-16 one. Such antibodies may be used for
      assay of L1-31 production in various expression systems.

PMID- 23547471
TI  - [The second generation universal oligonucleotide microarray for subtyping of
      influenza virus A].
AB  - The microchip for influenza A subtyping was developed, functioning on a principle
      "one spot--one subtype". Each spot contains the set of oligonucleotide probes,
      specific for a particular subtype of hemagglutinin, neuraminidase or matrix gene.
      Reliability of the proposed chip version is the same as for earlier created in
      our group full-size microchip for separate hemagglutinin and neuraminidase
      subtyping. To visualize the image, analyzed DNA can be labeled by either
      fluorescent dye or biotin with the further fixation in system streptavidin-gold
      nanoparticles and image development by silver precipitation. In the second case
      common version of scanner can be used for the image analysis, that essentially
      simplifies procedure of influenza A subtyping.

PMID- 23547472
TI  - [Amyloid-like fibrils forming and fibroblasts destruction in Tenon's capsule in
      progressive myopia as a result of pigment epithelium derived factor resistance to
      restricted proteolysis].
AB  - We have shown previously the presence of full length (50 kD) and truncated
      proteolytic form (45 kD) of pigment epithelium derived factor (PEDF) in the eye
      Tenon's capsule in progressive myopia. The full length PEDF is prevalent in
      myopia that correlates with breach in collagen fibrils forming.
      Immunohistochemical analysis of Tenon's capsule with polyclonal antibodies to
      PEDF revealed PEDF in control group being exclusively inside fibroblasts, whereas
      in myopia, PEDF was distributed extracellularly as halo around blasted
      fibroblasts. By means of atomic force microscopy and immunodot analysis with anti
      amyloid fibrils antibodies the ability was studied of recombinant PEDF fragments
      to form fibrils. Only full length PEDF was shown to form amyloid like fibril
      structures, but not the truncated form. Accumulation offibrils results in
      fibroblasts destruction and might be the cause of changes in biochemical and
      morphological structure of Tenon's capsule observed in myopia.

PMID- 23547473
TI  - [Composites of peptide nucleic acids with titanium dioxide nanoparticles. I.
      Construction of nanocomposites containing DNA/PNA duplexes and their delivery
      into HeLa cells].
AB  - In order to investigate the possibility of using titanium dioxide (TiO2)
      nanoparticles to transport peptide nucleic acids (PNA) in eukaryotic cells, a PNA
      oligomer has been synthesized, and method of PNA immobilization in the form of
      hybrid DNA/PNA duplexes on the surface of TiO2 nanoparticles covered with
      polylysine (PL) has been designed. Attaching of DNA/PNA duplex on TiO2 x PL
      nanoparticles occurred due to electrostatic interactions between the negatively
      charged DNA chain and the positively charged amino groups of PL. Binding of the
      PNA with the nanocomposite achieved through noncovalent Watson-Crick interactions
      between the PNA and complementary DNA. The capacity of obtained TiO2 x PL x
      DNA/PNA nanocomposites depending on immobilization conditions was 10-30 nmol PNA
      per 1 mg of TiO2 particles, which corresponds to -1-3 PNA molecules per one TiO2
      particle with size of 4-6 nm. By method ofconfocal laser scanning microscopy on
      the example of the fluorescein labeled PNA oligomer (Flu)PNA it has been shown
      that the PNA molecules in composition of TiO2 x PL x DNA/(Flu)PNA nanocomposites
      effectively penetrate and accumulate in HeLa cells without the use oftransfection
      agents, electroporation, or other auxiliary procedures has been shown.

PMID- 23547474
TI  - [Oligonucleotide derivatives in the nucleic acid hybridization analysis. III.
      Synthesis and investigation of properties of oligonucleotides, bearing
      bifunctional non-nucleotide insert].
AB  - Non-nucleotide phosporamidites were synthetized, having branched backbone with
      different position of functional groups. Obtained phosphoramidite monomers
      contain intercalator moiety--6-chloro-2-methoxyacridine, and additional hydroxyl
      residue protected with dimethoxytrityl group or with tert-butyldimethylsilyl
      group for post-synthetic modification. Synthesized oligothymidilates contain one
      or more modified units in different positions of sequence. Melting temperature
      and thermodynamic parameters of formation of complementary duplexes formed by
      modified oligonucleotides was defined (change in enthalpy and entropy). The
      introduction of intercalating residue causes a significant stabilization of DNA
      duplexes. It is shown that the efficiency of the fluorescence of acridine residue
      in the oligonucleotide conjugate significantly changes upon hybridization with
      DNA.

PMID- 23547475
TI  - Synthesis and antimicrobial activity of novel benzo[f]coumarin compounds.
AB  - The acetyl benzo[f]coumarin condensed with phenyl hydrazine to afford the
      corresponding phenyl hydrazone which cyclized into the pyrazolyl benzocoumarin
      under Vilsmeier reaction conditions. The pyrazolylaIdehyde was used as starting
      material for synthesis of other heterocyclic compounds containing
      pyrazolylbenzocoumarin moiety. The ethyl benzo[f]coumarin carboxylate were
      subjected to react with other reagents to synthesize thiazolidinyl and
      oxadiazolyl derivatives attached to benzocoumarin system. Some of novel
      synthesized compounds showed highly antibacterial and antifungal activities.

PMID- 23547476
TI  - [Ionic conjugates of sulfate carboxymethyl cellulose with dialkylaminomethyl
      derivatives of 2-isobornyl-4-methylphenol: synthesis and study of anti
      inflammatory and analgesic activity].
AB  - Water-soluble sulfate polysalts of carboxymethyl cellulose and tertiary
      aminomethyl derivatives of 2-isobornyl-4-methylphenol was obtained. For the
      synthesized conjugates investigated in vivo anti-inflammatory activity in the
      test of acute formalin inflammation and analgesic activity in tests the "hot
      plate" and "vinegar cramps".

PMID- 23547477
TI  - [Absorption of iodofolic acids by the cells of malignant tumors].
AB  - The uptake of 125-iodine labeled 3' iodofolic acid (I*F) and 3' iodo, 5 formyl
      tetrahydrofolic acid (I*FT) by the cells HeLa, ECV, L-41, human glioma, and rat
      glioma was studied. Human Embrionic Lung Fibroblasts (HELF) were taken for
      comparison as healthy cells. It was shown for *IF that its long-term uptake by
      cells L-41 and ECV is hundreds oftimes higher than those of HELF cells. The short
      term uptake phase was studied for *IFT uptake. The dissociation constant was
      determined for a complex formed by *IFT and an acceptor in the HeLa cells, which
      is supposed to cause concentrative uptake of *IFT in cells. The dissociation
      constants of this acceptor complexes with folic acid, 3' iodofolic acid and 3',5'
      diiodofolic acid were determined by competition with I*FT. The distribution ratio
      of *IF and *IFT in tissues of different organs of healthy mice and rats and rats
      with a sarcoma grafted on his thigh and glioma grafted into the brain was
      studied. As was shown there are large differences in the concentration of *IF and
      *IFT in the tumor and in the healthy tissue, *IF concentration in thigh muscle of
      healthy being 5 times lower than those in tumor grafted to the thigh, and *IFT
      concentration in healthy brain being 10 times lower than in brain tumor.

PMID- 23547478
TI  - [A convenient approach to the synthesis of the phosphoramidite non-nucleotide
      monomers for the preparation of functionalized oligonucleotide derivatives].
AB  - A simple approach to the synthesis of phosphoramidite synthons for non-nucleotide
      inserts using 4-(2-(4,4'-dimethoxytrityloxy)ethyl)morpholine-2,3-dione as a key
      precursor is suggested. Using the method developed various inserts have been
      introduced into oligonucleotides to obtain intercalator-containing (acridine) as
      well as branched oligonucleotides.

PMID- 23547479
TI  - [Evaluation of TB-beads assay utilizing the technique of magnetic beads--an
      innovative assay method for detection of acid fast bacilli].
AB  - The centrifuge method with the use of Semi-Alkalin Proteinase (SAP) and NALC
      NaOH, recommended by the "2007 edition of the assay guideline for detection of
      Mycobacterium tuberculosis," has significantly contributed to improving the
      sensitivities and specificities of both smear and culture tests for detection of
      acid fast bacilli (AFB). However, this method poses some challenges in terms of
      its cumbersome and time-consuming assay protocol. "TB-beads (Kyokuto
      Pharmaceutical Industrial Co., Ltd.)" is a newly-developed method for detection
      of AFB utilizing magnetic beads. We evaluated the quality of this method in
      comparison with the centrifuge method, focusing on the results of smear and
      culture tests. This evaluation study was conducted using both 5 positive and 5
      negative sputum samples. The sensitivity of TB-beads for fluorescent smear tests,
      conducted using "Acri-stain," was almost the same as that of the centrifuge
      method. One advantage of TB-beads, however, was that it was very convenient to
      practice microscopic observation due to the clear background of the smeared glass
      slides. The comparison of the contamination rates between the two methods showed
      that TB-beads suggested significantly lower contamination rates. The centrifuge
      method resulted in 50% and 60% of contamination rates for HK Semisolid Isolation
      Medium and BacT/ALERT MP, respectively. On the other hand, the contamination
      rates of TB-beads for both of the culture methods were only 10%. With regard to
      the 5 positive sputum samples, the comparison of the detection rates between the
      centrifuge and TB-Beads method was made utilizing Myco Acid, Ogawa K, and
      BacT/ALERT MP. The TB-Beads method suggested higher detection rates for Myco Acid
      and Ogawa K, while there were no significant differences between the two methods
      for BacT/ALERT MP (16-23 days). TB-beads is an easy method that allows to
      simplify the process of smear tests, and contributes to significantly reducing
      the contamination rate of culture tests. It also contributes to improving the
      sensitivity and detection rate of AFB testing. Furthermore, it does not require
      centrifugation. Ultimately, TB-beads is an innovative, safe, and convenient
      testing method for detection of AFB, which enables laboratory technicians to save
      time for routine work.

PMID- 23547480
TI  - [Investigation on the identification accuracy for group B Streptococcus by
      automated identification system RAISUS].
AB  - Since we had experienced a case of misidentification for group B Streptococcus
      (GBS) (Streptococcus agalactiae) by automated identification system RAISUS, we
      have investigated the identification accuracy for GBS by automated identification
      system RAISUS system using our stock isolated of GBS. Among 31 strains including
      standard strain ATCC13813 of GBS, 30 strains were identified as GBS, while only 1
      strain was misidentified as Streptococcus constellatus. We have needed 3 hours to
      identify 29 true GBS strains, while it has taken 6 hours for misidentified strain
      as S. constellatus. Since we have needed more than 4 hours for our misidentified
      strain of GBS, the tendency for identification time to become long has been
      recognized. Longer identification time might be associated with the
      misidentification. The improvement for galactose and glycerol tests of RAISUS by
      the manufacturer has resulted in better identification. As for the strains to be
      identified as S. constellatus by RAISUS, we might re-check it with other
      identification kits when there is higher clinical necessity.

PMID- 23547481
TI  - [Pandemic influenza].

PMID- 23547482
TI  - [Applications of MALDI-TOF mass spectrometry in today's and tomorrow's clinical
      microbiology laboratory].

PMID- 23547483
TI  - [Infectious disease after the great Hanshin-Awaji earthquake and the contribution
      of rapid diagnosis in microbiology].

PMID- 23547484
TI  - [Contribution of the rapid diagnostic tests for infectious diseases to the
      patient management in the Great East Japan earthquake].
AB  - On 11 March 2011, an earthquake measuring 9.0 on the Richter scale off the
      northeast coast of Honshu Island, Japan, produced a devastating tsunami that
      destroyed many towns and villages near the coast in Iwate, Miyagi, and Fukushima
      prefectures. Miyagi Prefecture was the area most severely devastated by the
      tsunami, with extensive loss of life and property; hundreds of thousands of
      people lost their houses and were forced to move to evacuation areas. In the days
      and weeks following devastating natural disasters, the threat of infectious
      disease outbreak is high. Rapid diagnostic tests can be performed at or near the
      site of patient care and the tests were very useful in this disaster, because
      they enabled us to manage patients appropriately in the settings where medical
      resources were limited. Here we report actual cases where the rapid diagnostic
      tests for infectious diseases were useful in the patient management.

PMID- 23547485
TI  - [Risk management in a microorganism test room].

PMID- 23547486
TI  - [Respiratory Viral Panel Detection Kit and Gastrointestinal Pathogen Panel
      Detection Kit using Luminex technology].

PMID- 23547487
TI  - Comparative plaque removal efficacy of a new children's powered toothbrush and a
      manual toothbrush.
AB  - OBJECTIVE: The purpose of this study was to determine the plaque removal
      effectiveness of a new children's powered toothbrush and compare it to that of a
      manual brush. METHODS: This examiner-blind, randomized study used a cross-over
      design. One-hundred and five qualifying male and female subjects (52 ages 8-12
      and 53 ages 13-17) were randomly assigned either the powered brush (Spinbrush
      GLOBRUSH) or a manual toothbrush (Oral-B Indicator 30 Compact Soft Toothbrush)
      and instructed to brush at home with a standard fluoride toothpaste twice daily
      for two minutes during a one-week familiarization period. At the end of this
      period, the subjects returned to the study site after refraining from oral
      hygiene for twenty-four hours and from eating and drinking for four hours. Plaque
      was scored using the Rustogi Modification of the Navy Plaque Index, subjects
      brushed under supervision with their assigned toothbrush for two minutes, and
      plaque was rescored. They were then given the alternate toothbrush and the
      familiarization routine and evaluation process were repeated. RESULTS: Within
      group analysis showed that both toothbrushes produced statistically significant
      reductions from the pre-brushing baseline in whole mouth and regional plaque
      scores (p < 0.0001), with respective whole mouth reductions of 73.3% and 61.8%
      for the powered brush and the manual brush. Between-group analyses showed that
      the powered brush produced a statistically significantly greater plaque reduction
      than the manual brush, both whole mouth (12.8%, p < 0.0001) and at all subset
      sites, including difficult-to-reach areas such as the posterior lingual gingival
      region (74.9% greater plaque reduction, p < 0.0001). CONCLUSION: The Spinbrush
      GLOBRUSH was significantly more effective in reducing plaque than the manual
      toothbrush when evaluated using this single-use clinical model.

PMID- 23547488
TI  - The staining potential of various currently marketed mouthrinses.
AB  - OBJECTIVES: The objectives of this clinical trial were to determine the tooth
      staining potential as measured by the Macpherson Modification of the Lobene Stain
      Index, and degree of taste alteration of four currently marketed mouthrinses when
      used over a 12-week period. METHODS: This investigation consisted of a 12-week,
      observer-blind, single-center, randomized comparison of five parallel groups of
      subjects. One-hundred and seventy-one subjects granting their informed consent
      completed the trial. Subjects were randomized to one of four currently marketed
      mouthrinses Crest PRO-HEALTH Rinse (CPH), Cepacol (C), Scope (S), Viadent
      ADVANCED CARE (V), or brushing alone (BA) with a currently marketed fluoride
      toothpaste. Upon randomization, subjects received a baseline stain score and then
      a prophylaxis to remove all extrinsic stain. Clinical assessments were repeated
      after six weeks and three months of product use, and subjects were asked to
      complete a questionnaire after the first use, at day 4, day 14, at six weeks, and
      12 weeks to assess potential taste alteration. RESULTS: CPH and C demonstrated
      significantly (p < 0.001) more extrinsic stain after six weeks of use, and CPH, C
      (p < 0.001), and S (p = 0.01) after 12 weeks of use versus brushing alone with
      fluoride toothpaste. V was not significantly different from brushing alone at
      either time point. After six weeks of using the product as directed, up to 53% of
      subjects using CPH experienced taste interference for up to three hours post
      rinse. CONCLUSIONS: The results of this study demonstrated that regular use of
      CPH and C mouthrinses resulted in extrinsic stain accumulation after six weeks,
      with increased accumulation after 12 weeks versus brushing alone.

PMID- 23547489
TI  - Short term clinical efficacy of new meridol HALITOSIS tooth & tongue gel in
      combination with a tongue cleaner to reduce oral malodor.
AB  - OBJECTIVE: This study evaluated the short term efficacy of tongue cleaning with
      meridol HALITOSIS tooth & tongue gel in comparison to mechanical tongue cleaning
      alone and untreated after five and 60 minutes in patients with an oral cause of
      bad breath. METHODS: Fifty-four male and female subjects with an intra-oral cause
      of halitosis (organoleptic ratings > or = 2 and volatile sulphur compounds > or =
      50 ppb) participated in this crossover study and were assigned to six different
      treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) with no treatment (A),
      mechanical tongue cleaning alone (B), and tongue cleaning with tooth & tongue gel
      applied to the tongue cleaner (C). Efficacy was assessed by organoleptic ratings
      and volatile sulphur compound measurements five and 60 minutes after treatment
      RESULTS: Cleaning the tongue with tooth & tongue gel applied onto the tongue
      cleaner resulted in significantly reduced organoleptic ratings (p < 0.001 for the
      five-minute assessment; p = 0.001 for the 60-minute assessment) and volatile
      sulphur compounds (H2S + CH3SH: p = 0.005 for the five-minute assessment; p =
      0.003 for the 60-minute assessment) compared to no treatment at the five- and 60
      minute assessment time points, while mechanical tongue cleaning alone was less
      effective in reducing organoleptic ratings (p = 0.008 for the five-minute
      assessment; p = 0.144 for the 60-minute assessment) and volatile sulphur
      compounds (H2S + CH3SH: p = 0.261 for the five-minute assessment; p = 0.365 for
      the 60-minute assessment). CONCLUSIONS: Single tongue cleaning with meridol
      HALITOSIS tooth & tongue gel had a positive effect on halitosis five and 60
      minutes after treatment. Tongue cleaning with tooth & tongue gel in combination
      with other oral hygiene procedures is a promising approach to control halitosis.

PMID- 23547490
TI  - Determination of plaque viability following a single brushing with commercial
      toothpastes.
AB  - OBJECTIVE: The purpose of this study was to determine the viability of dental
      plaque at 12 hours following brushing with Colgate Great Regular Flavor (0.83%
      MFP), Crest Pro-Health (0.454% SnF), and Colgate Total Clean Mint Toothpaste
      (0.3% triclosan/ copolymer/0.22% NaF). METHODS: Thirty-two healthy volunteers
      from Bangkok, Thailand were chosen to participate in a double-blind clinical
      crossover study for three one-week treatment periods. They were randomly assigned
      to three groups using different sequences of test toothpastes. The plaque samples
      were collected at baseline (prior to brushing) and 12 hours after brushing with
      assigned toothpastes at the scheduled appointments. Scores and percentages of
      plaque viability were examined under a fluorescent microscope using a mixture of
      40 microl of green and red fluorescent dyes, and were statistically analyzed
      using a two-way ANOVA. RESULTS: Plaque viability scores and percent plaque
      viability at baseline with all test toothpastes showed no significant differences
      with a p-value > 0.05. The post-treatment mean values of plaque viability scores
      for Colgate Great Regular, Crest Pro-Health, and Colgate Total 12 hours after
      brushing were 1.39, 3.01, and 3.37, and represented 90.06, 49.80, and 40.77
      percent viable plaque, respectively. The Analysis of Variance (ANOVA) showed
      statistically significant differences when comparing Colgate Great Regular and
      Crest Pro-Health, Colgate Great Regular and Colgate Total, and Crest Pro-Health
      and Colgate Total using Tukey's test with a p-value < 0.001. CONCLUSION: Colgate
      Total, containing triclosan/copolymer/NaF as the active ingredients, is effective
      and superior to Crest Pro-Health and Colgate Regular in controlling the viability
      of oral bacteria in dental plaque.

PMID- 23547491
TI  - Enamel protection from acid challenge--benefits of marketed fluoride dentifrices.
AB  - OBJECTIVE: To determine the ability of various marketed dentifrices containing
      stabilized stannous fluoride (SnF2), sodium fluoride (NaF), or sodium
      monofluorophosphate (SMFP) to protect enamel against the earliest stages of
      erosive dietary acid damage using an in vitro enamel protection model. METHODS:
      Acid-challenged, extracted human teeth were treated with a 1:3 dilution of
      dentifrice, rinsed, and then challenged in a controlled series of tests using
      four dietary acids considered potentially erosive to teeth. Each acid was
      collected and analyzed to determine the level of mineral (phosphorous) removed
      from the teeth during the challenge. Post-treatment results were compared to
      baseline values for each acid. Results for the four acids were averaged and
      reported as an average percent protection value for each of the dentifrices
      tested, with higher values representing greater acid protection. The study
      included six dentifrices formulated with (A) sodium fluoride (NaF), (B)
      stabilized stannous fluoride (SnF2), (C,D) NaF plus 5% potassium nitrate (KNO3),
      (E) sodium monofluorophosphate (SMFP), or (F) SMFP plus 8% arginine bicarbonate.
      RESULTS: The stabilized SnF2 dentifrice demonstrated an average protection score
      of 39.3%, while products formulated with NaF resulted in protection scores
      between 11 and 13%. The SMFP dentifrice was rated at -3.5%, and the SMFP +
      arginine bicarbonate dentifrice resulted in a net average score of -5.0%. Results
      of this test were statistically significant (p < 0.05, ANOVA: B > A = C = D > E =
      F), in favor of the stabilized SnF2 dentifrice. CONCLUSIONS: These results
      suggest the stabilized SnF2 dentifrice has the potential to provide significantly
      better overall acid protection versus any of the other dentifrices included in
      the study.

PMID- 23547492
TI  - Plaque control evaluation of a stabilized stannous fluoride dentifrice compared
      to a triclosan dentifrice in a six-week trial.
AB  - OBJECTIVE: To compare the anti-plaque efficacy of a stabilized 0.454% stannous
      fluoride (referred to as SnF2) dentifrice versus a 0.3% triclosan dentifrice
      formulated with a copolymer and sodium fluoride (referred to as triclosan).
      METHODS: The study had a randomized, double-blind, two-treatment, parallel-group
      design, and compared plaque reduction from baseline after both three and six
      weeks of treatment with either the SnF2 or triclosan dentifrices using a manual
      toothbrush. Subjects brushed their teeth using their assigned treatment
      dentifrices according to the manufacturer's instructions. Following overnight
      plaque accumulation, levels of plaque were assessed by an experienced examiner
      using the Rustogi, et al. Modified Navy Plaque Index at the start of the study
      (baseline), and after three and six weeks of regular brushing. Groups were
      compared using analysis of covariance separately for Weeks 3 and 6, and by
      repeated measures for Weeks 3 and 6 combined. RESULTS: One-hundred and twenty
      subjects were randomized to treatment and 114 subjects completed the study. Both
      treatment groups showed a statistically significant reduction from baseline in
      mean plaque values for all three tooth areas (whole mouth, gingival margin,
      interproximal) at both Weeks 3 and 6 (p < 0.02 for all comparisons). Analysis of
      covariance showed a statistically significantly (p < 0.0001) lower adjusted mean
      plaque level for the SnF2 group compared to the triclosan group for all three
      tooth areas at both Weeks 3 and 6, and for Weeks 3 and 6 combined. Weeks 3 and 6
      combined adjusted mean plaque was 36.5% lower for whole mouth for the SnF2 group
      versus the triclosan group. Weeks 3 and 6 combined adjusted mean plaque reduction
      from baseline was three times greater for the SnF2 group relative to the
      triclosan group. CONCLUSION: Both dentifrices showed statistically significant
      reductions from baseline in whole mouth, gumline, and interproximal accumulated
      overnight plaque after three and six weeks of brushing, but the SnF2 dentifrice
      showed statistically significantly greater plaque reductions versus the triclosan
      dentifrice.

PMID- 23547493
TI  - Kicking-off the New Year with Medicare adjustments taking effect.

PMID- 23547494
TI  - Establishment of a university academic spine center: from concept to reality.
AB  - In fewer than five years, the University of Kansas Hospital Spine Center became
      the largest and most comprehensive spine care facility in the greater
      metropolitan Kansas City area. The 22,000-square-foot facility has 27 exam rooms,
      four specialized diagnostic rooms, 11 pre-/post-interventional procedure rooms,
      and a 4000-square-foot outpatient rehabilitation gym. Patients can meet with
      their physicians, undergo diagnostic tests and treatment, and attend therapy
      sessions in one location. The multidisciplinary Spine Center brings together
      orthopedic surgeons, neurosurgeons, neurologists, physical medicine and
      rehabilitation physicians, psychiatrists, psychologists, pain-management
      anesthesiologists, radiologists, and physical and occupational therapists. The
      Spine Center became successful because a group of physicians bought into the
      philosophy of a comprehensive interdisciplinary program, were willing to
      sacrifice some territorial claims, and were willing to put patient care and the
      good of the institution above individual egos.

PMID- 23547495
TI  - Strategic planning: how medical practices can succeed in a post-healthcare-reform
      world.
AB  - This article addresses the recent trend of physicians being pressured to sell to
      hospitals in order to stay in practice. The author utilizes his experience in the
      healthcare industry to identify causes of this trend and ways in which physician
      groups can avoid finding themselves in these situations. The author uses real
      data from an existing medical practice to support his ideas and demonstrate how
      implementing change now will be beneficial for the success of this medical
      practice in the future. Objective practice evaluation and the execution of an
      efficient strategic plan are cited as the most important factors contributing to
      the financial solvency of medical practices in the current and future healthcare
      environment.

PMID- 23547496
TI  - Making a difference.
AB  - The role of a leader is to make a difference in his or her organization. Success
      in making a difference involves focusing attention in three areas: the climate,
      the development of staff, and a focus on the future. There are specific things
      that leaders can do to become more effective in improving their organization.

PMID- 23547497
TI  - Academic medicine in turbulent times.
AB  - Long respected as centers of research and educational excellence, many
      traditional academic medical centers (AMCs) realize that their research and
      educational missions will be difficult if not impossible to sustain, if all the
      federal funding cuts discussed in anticipation of the "fiscal cliff" occur. To
      set the context for this perfect storm, we will review the many issues that will
      affect all hospitals and then focus on the three that will disproportionally
      affect academic medical centers ... and keep "CEOs up at night." Aside from a
      case of CEO chronic insomnia, how do we expect AMCs to weather this perfect
      storm? Whereas the fundamental emphasis remains on highly specialized and complex
      care, AMCs are increasingly developing innovative approaches for managing
      patients across the continuum of care and strengthening their ability to manage
      patients with high-cost, chronic conditions.

PMID- 23547498
TI  - Fostering collaboration in the medical practice: twenty-five tips.
AB  - It's a given that collaboration is an important aspect of medical practice
      management. But achieving genuine collaboration among the members of your medical
      practice team may not be as simple as it seems. This article suggests 25
      practical strategies for medical practice employees and their managers to help
      them create and foster collaboration in their medical practices. Tips for
      collaborative goal setting, communication, ground rules, task delineation,
      sustainability, problem solving, and anticipating and handling problems are all
      described. In addition, this article offers a four-step strategy for dealing with
      a domineering collaborator and a five-step strategy for dealing with a
      collaboration slacker. This article also includes a 20-question self-quiz to help
      you and your employees evaluate your collaborative work style. Finally, this
      article describes 10 common collaboration pitfalls and the strategies you and
      your staff can use to avoid falling victim to them.

PMID- 23547499
TI  - All work (RVUs) and no pay?: eight questions to ask the hospital about its work
      RVU compensation formula.
AB  - As more surgeons and specialists are offered hospital employment, work RVU-based
      compensation agreements are becoming more sophisticated and complex. In order to
      have a meaningful conversation with health system administrators and ensure that
      a compensation agreement addresses all issues pertinent to the physician's
      practice and specialty, physicians must familiarize themselves with the nuances
      of work RVU-based compensation formulas, as well as the national benchmarking
      standards, CPT guidelines, and reimbursement rules that impact them. The eight
      questions developed for this article are the result of reviewing multiple
      compensation agreements between physicians and hospitals and can help physicians
      drive the conversation with health system administrators. Engaging the services
      of a healthcare attorney or physician compensation expert for these conversations
      is advised.

PMID- 23547500
TI  - How risk assessment helps build a solid compliance work plan.

PMID- 23547501
TI  - Understanding how the Physician Quality Reporting System affects primary care
      physicians.
AB  - The Physician Quality Reporting System (PQRS) uses a combination of payment
      incentives and adjustments to promote reporting of quality information by
      eligible professionals who satisfactorily report data on quality measures for
      covered Physician Fee Schedule services furnished to Medicare Part B Fee-for
      Service beneficiaries. Physicians should become familiar with the PQRS core
      measures to maintain compliance with the Centers for Medicare & Medicaid
      Services. Adherence to these basic guidelines will allow physicians to not only
      maximize their income, but also increase quality of care, decrease complications,
      and decrease healthcare expenditures.

PMID- 23547502
TI  - Steve Jobs provides lessons for any medical practice.
AB  - Steve Jobs is inarguably the greatest inventor and creative genius since Thomas
      Edison. He provided technology that enhances communication on a global level.
      Jobs also provided ideas and suggestions that could work in any medical practice
      regardless of the size of the practice, the location of the practice, or the
      employment model. His advice can be transferred from a high-tech business that
      employs thousands to a high-touch medical practice that has only a few employees.
      This article will list a few of Jobs leadership characteristics and how they
      might apply to physicians, their teams, and their practices. Wouldn't you like to
      be the Steve Jobs of healthcare? If so, read on!

PMID- 23547503
TI  - Hospital reimbursement incentives: is there a more effective option?--Part II.
AB  - As discussed in Part I of this article, hospital executives in Canada, Germany,
      and the United States manage their facilities' resources to maximize the
      incentives inherent in their respective reimbursement system and thereby increase
      their bottom line. It was also discussed that an additional supply of available
      hospitals, physicians, and other services will generate increased utilization.
      Part II discusses how the Patient Protection and Affordable Care Act of 2010 will
      eventually fail since it neither controls prices nor utilization (e.g., imaging,
      procedures, ambulatory surgery, discretionary spending). This article concludes
      with the discussion of the German multipayer approach with universal access and
      global budgets that might well be a model for U.S. healthcare in the future.
      Although the German healthcare system has a number of shortfalls, its paradigm
      could offer the most appropriate compromise when selecting the economic
      incentives to reduce the percentage of the U.S. gross domestic product
      expenditure for healthcare from 17.4% to roughly 12.0%.

PMID- 23547504
TI  - Feeling powerless?

PMID- 23547505
TI  - Physician-hospital alignment: "employment lite".
AB  - The American healthcare delivery system is undergoing a major change that
      involves independent solo and small groups of doctors becoming employed by
      hospitals. Some describe this as a paradigm shift; we view it as a tsunami that
      is engulfing physicians across the nation. This phenomenon is unfamiliar to most
      physicians and represents huge risks with the shift from private, fee-for-service
      practices to practicing as an employee of a hospital. This article discusses the
      pitfalls associated with the transfer to a hospital employee using a concept
      called "employment lite." It presents the advantages and disadvantages of
      employment lite and why this might serve as an alternative to a fully employed
      hospital physician. The employment lite option is similar to employment in that
      it allows the physician to enjoy most of the nuances of employment, yet maintain
      a desirable level of independence.

PMID- 23547506
TI  - Computer briefs: privacy, M-health, and social media.

PMID- 23547507
TI  - Current research in the pathogenesis of aseptic implant loosening associated with
      particulate wear debris.
AB  - Periprosthetic osteolysis is the most common long-term complication of a total
      joint arthroplasty, often resulting in aseptic loosening of the implant, which
      occurs in up to 34% of younger implant recipients and usually requires surgical
      revision. Particulate wear debris, continuously generated by articulating motion
      at the bearing surfaces, has been implicated as one of the primary causes of
      periprosthetic bone loss and implant loosening. With developing implants and
      bearing surfaces designs, various types of wear particles with specific chemical
      nature, dimension and shape are formed, which may initiate different immune or
      inflammatory responses. Wear debris induces down-regulation or up-regulation of
      various pro-inflammatory cytokines and chemokines in a range of cell types at the
      interface between implants and the surrounding bone, such as macrophages,
      osteoclast precursor cells, osteoblasts, lymphocytes, fibroblasts etc.
      Concomitantly, these mediators further affect functions of cells through distinct
      signaling mechanisms in either an autocrine or a paracrine manner. This review
      summarizes current concepts of how wear debris causes osteolysis, and describes
      the interaction and effects of wear debris on functions of primary cell types
      involved in osteolysis.

PMID- 23547508
TI  - Platelet-rich plasma application in the management of chronic tendinopathies.
AB  - Platelet-rich plasma (PRP) may represent a new therapeutic option for chronic
      tendinopathies. Platelets release various cytokines and growth factors which
      promote angiogenesis, tissue remodeling, and wound healing. We made an extended
      literature review of the use of PRP in chronic tendinopathies: epicondylitis,
      rotator cuff, patellar and calcaneal tendinopathies, and plantar fasciitis.
      Medline, Embase and Google Scholar were used (until July 31, 2012). Clinical
      studies on PRP and tendinopathies published in English and French language peer
      reviewed journals were included. Articles with a high level of evidence were
      given special consideration. Despite the proven efficacy of PRP on tissue
      regeneration in experimental studies, there is currently scanty tangible clinical
      evidence with respect to its efficacy in chronic tendon disorders. The few
      studies that have been performed appear unlikely to be comparable. Randomized
      controlled studies with appropriate placebo groups are needed to determine the
      real effectiveness of PRP for treating chronic musculoskeletal injuries.

PMID- 23547509
TI  - Pseudoaneurysm after total knee arthroplasty: a rare complication with different
      possible clinical presentations.
AB  - We report three cases of false aneurysm involving the popliteal artery or one of
      its branches following total knee replacement. Two of them developed after
      primary total knee arthroplasty (TKA) and the third one after a revision TKA.
      False aneurysm is a rare complication of TKA. The main symptom is generally a
      painful pulsatile mass which develops postoperatively but our cases occurred with
      three distinct clinical manifestations. Doppler ultrasonographic and angio-CT
      investigations were used to achieve the correct diagnosis. Two patients were
      treated by percutaneous embolization; the third patient required a mini-open
      surgery with an endovascular prosthesis. No complications were encountered.

PMID- 23547510
TI  - Postsurgical Parsonage-Turner syndrome: a challenging diagnosis.
AB  - Parsonage-Turner syndrome (PTS) is a distinct clinical syndrome, characterized by
      acute and severe (mostly) unilateral shoulder pain, followed by paresis and
      atrophy of the shoulder girdle, while the pain decreases. Most authors consider
      it as an immune-mediated disorder. PTS is notoriously unrecognised and is usually
      diagnosed with delay. A PTS may also occur following a surgical procedure.
      Postsurgical PTS is an under-recognised and challenging clinical entity, as
      illustrated in the case reported here of a 59-year-old man, 4 weeks after
      anterior discectomy and fusion C5C7. In such cases, the differential diagnosis
      must be made with a complication of surgery, such as postoperative C5 palsy due
      for instance to a migrated bone graft. Arguments for PTS are: a certain delay
      between surgery and symptoms, intolerable pain followed by weakness and
      improvement of pain complaints, divergent distribution of weakness, sensory
      deficit and pain, which may be confirmed by electrodiagnosis. Early recognition
      of postsurgical PTS may avoid unnecessary investigations or surgical exploration.
      It allows to treat the patient properly, leading to greater satisfaction of both
      surgeon and patient; pain management, physical therapy and reassurance are the
      cornerstones.

PMID- 23547511
TI  - Platelet-rich fibrin in arthroscopic repair of massive rotator cuff tears: a
      prospective randomized pilot clinical trial.
AB  - The objective of this study was to prospectively evaluate the feasibility of a
      large- scale project on the influence of local application of Platelet Rich
      Fibrin (PRF) on the functional outcome and integrity of the arthroscopically
      repaired tendons in patients with massive tears of the rotator cuff. A
      prospective, randomized pilot clinical trial was performed on 28 patients (22
      females, 6 males) with an average age of 65 years (range: 53 to 77) undergoing
      complete arthroscopic repair of a massive rotator cuff tear. After the repair was
      completed, 6 ml PRF (Vivostat) was locally applied to the repair site in 14
      patients; no similar action was done in the other 14 patients. All patients
      underwent a clinical examination and an arthro-MRI to evaluate the integrity of
      the repair, one year after the operation. They were followed clinically for a
      minimum of 2 years. Functional outcome was evaluated with the Constant and DASH
      scores. There were no reported complications in either group. None of the
      patients was lost to follow-up. Globally, the Constant score improved from 45
      preoperatively (range: 25 to 65) to 64 at one year (range: 20 to 79) (p < 0.001),
      with no significant change at two years (mean 63, range: 20 to 77). The VAS for
      pain improved from 5.6/10 preoperatively to 1.7/10 at the most recent examination
      (p < 0.001). All but two patients were satisfied. With the numbers of patients
      available, we could not detect a significant difference in the preoperative (46
      vs. 43; p = 037) or postoperative Constant score (61 vs. 68; p = 0.125) between
      the control group and the PRF group. On arthro-MRI, 19 of the 28 patients (68%)
      were found to have a large re-tear : 10/14 in the PRF group and 9/14 in the
      control group. Local application of autologous PRF to the repair site of massive
      rotator cuffs fully reconstructed arthroscopically failed to improve the clinical
      outcome and the healing rate, compared with a standard repair. However, a large
      scale study would be necessary to confirm these results.

PMID- 23547512
TI  - The 'hand squeeze' test for posterior 'muscle patterning instability' of the
      shoulder.
AB  - Muscular patterning can be a contributor of positional posterior shoulder
      instability. Failure to recognize this pattern may lead to unnecessary surgical
      treatment with high failure rate. We analyzed the results of a new simple
      clinical test (hand squeeze test). The test is regarded positive, if during
      squeezing with the contralateral hand and elevation of the involved arm, in
      pronation, no posterior shoulder dislocation occurs. The test is regarded
      negative if posterior dislocation does occur regardless of the "hand squeeze".
      The patients with positive test were treated conservatively. Ten patients (12
      shoulders) were treated between July 2006 and July 2010. The 'hand squeeze' test
      was positive in 8 patients (10 shoulders) and negative in 2 patients (2
      shoulders). Both patients with a negative sign had structural lesions in the
      glenohumeral joint confirmed on arthro-MRI and were treated operatively.

PMID- 23547513
TI  - Biomechanical comparison of indirect and direct arthroscopic excision of the
      distal clavicle.
AB  - The purpose of this study was to compare the stability and force of ultimate
      failure of the acromioclavicular joint (ACJ) after direct arthroscopic distal
      clavicle excision (DCE) through superior portals and indirect arthroscopic DCE
      through inferior portals in paired cadaveric shoulders. Ten paired saline
      embalmed cadaveric shoulders were operated alternatively using the indirect and
      direct technique. Biomechanical testing was performed in the horizontal plane,
      testing displacement at 15N and 30N and finally failure strength was measured
      testing the constructs until failure occurred. There was a significant difference
      in failure strength with the direct DCE being stronger: 766.6 N (SD 233.5)
      against 5403 N (SD 239.1) for the indirect DCE, p = 0.01334). There was no
      statistical difference for the displacement measured at 15N and 30N. A direct DCE
      will result in a postoperative ACJ with greater ultimate failure strength
      compared to indirect DCE because the inferior ACJ capsule can be better
      preserved.

PMID- 23547514
TI  - The use of the three-point index in the management of extra-articular distal
      radius fractures.
AB  - Conservative management has been the mainstay of treatment for simple extra
      articular distal radius fractures. Several factors, such as quality of definitive
      casting, have been implicated in the risk of fracture re-displacement during
      follow-up. Objective assessments of the quality of casting using various indices
      have been documented in literature, although overall evidence remains scant, and
      only one study in the literature discusses the use of the three-point index (3
      PI) in adults. Currently, no independent study assessing the 3-PI in adults has
      been documented. This retrospective study aimed to assess the 3-PI in terms of
      (1) predicting fracture re-displacement and (2) evaluating its practicality in
      everyday clinical use. We had 54 patients (47 female, 7 female), out of which 35
      patients had a 3-PI greater than the suggested cutoff value of 0.8; of these, 22
      went on to re-displace. The remaining 19 patients had a 3-PI below the cutoff and
      14 went on to re-displace. No statistical significance was found for the 3-PI as
      a predictor for fracture re-displacement, although inter-observer reliability was
      high; its impact on clinic times (in calculating the 3-PI) remained low.

PMID- 23547515
TI  - Fracture of the ulnar styloid process negatively influences the outcome of
      paediatric fractures of the distal radius.
AB  - In paediatric patients with fractures of the distal radius, the consequences of
      associated ulnar styloid fractures are often underestimated. These may include
      persisting pain or functional deficits. The aim of the present study was to
      report the outcome of these fractures using a modified DASH-Score. All children
      with distal radius fractures treated in a two years period were analysed; only
      patients with a concomitant fracture of the ulnar styloid were included in the
      study.In addition, children with a non-union of the styloid at cast removal were
      asked to complete a postal questionnaire; the data were compared to those in a
      group of patients with isolated distal radius fractures. Patients reporting
      problems and those with a modified DASH score over 0.5 were invited for a long
      term follow-up clinical and radiological examination. A concomitant fracture of
      the ulnar styloid was present in 11% of all distal radius fractures. At the time
      of cast removal 46 patients (89%) showed a delayed union of the ulnar styloid.
      The modified DASH Score of these patients at an average of 31 months (range: 24
      40 months) was significantly worse (3.8; range: 0-24.2) compared to 0.7 (range 0
      27.7) in the patients with isolated radius fractures after a mean of 27 months
      (range: 21-42 months). At follow-up, 7 patients showed a non-union of the ulnar
      styloid. Fractures of the base of the styloid process were more likely to develop
      non-union compared to fractures of its tip. The presence of an ulnar styloid
      fracture negatively influences the outcome of distal radius fractures. Patients
      with lesions of the ulnar styloid should be followed until union is observed
      and/or they are asymptomatic.

PMID- 23547516
TI  - Endobutton technique for dynamic fixation of traumatic symphysis pubis
      disruption.
AB  - Plate fixation, the conventional treatment for traumatic symphysis pubis
      disruption, carries the risk of implant failure and demands extensive exposure.
      The goal of the present study was to evaluate the outcome of dynamic fixation
      with the Endobutton CL, which has a long successful record in anterior cruciate
      ligament reconstructions. Twenty-one APC-II injuries were treated from January
      2006 to December 2009. The mean duration of follow-up was 23 months (18 to 26).
      All patients received Endobutton fixation. The incision length was 6.8 +/- 13 cm.
      The external blood loss was 106 +/- 15 mL. The average surgical time was 63 +/-
      12 min. The symphysis distance after reduction was 4.1 +/- 1.2 mm. The symphysis
      distance at final visit was 4.2 +/- 1.2 mm. Loss of reduction was not significant
      during bone healing (p = 0.09). The Majeed scoring was excellent in 15 patients,
      good in 5 patients and fair in 1 patient. One malreduction was seen; there was no
      implant failure. Our results indicate that Endobutton fixation of the pubic
      symphysis might be used in the treatment of APC-II injuries.

PMID- 23547517
TI  - Walking quality after surgical treatment of developmental dysplasia of the hip in
      children.
AB  - We assessed the quality of life of children with developmental dysplasia of the
      hip (DDH) treated surgically, through analysis of leg length discrepancy, quality
      of walking and presence of pain in 39 children with DDH between 1991 and 2011 at
      the University Children's Hospital in Belgrade. Salter's innominate osteotomy
      combined with derotation and femoral bone shortening was performed. Patients were
      divided into 3 groups based on their age at operation: the first group included
      participants operated at age up to 24 months, the second group between 24 and 48
      months and the third group above 48 months of life. In the first group, leg
      length discrepancy was present in 30.76% and mean leg shortening was 0.63cm,
      versus 27.77% and 1.30 cm in the second group and 37.50% and 1.50 cm in the third
      group. Children with DDH that were operated earlier in life had less leg
      shortening and did not display any significant asymmetry of walking.

PMID- 23547518
TI  - Impaction bone grafting of segmental bone defects in femoral non-unions.
AB  - Impaction bone grafting shows encouraging early results as a method of
      immediately restoring leg length, while allowing weight-bearing as tolerated, in
      the treatment of large segmental femoral defects after femoral shaft and
      metaphyseal non-unions. The operative technique followed is described in three
      consecutive cases and the effectiveness of impaction bone grafting for femoral
      non-unions with associated large segmental bone defects has been demonstrated.
      Between 80 and 120 cm3 of coarsely milled irradiated bone allograft was used to
      reconstruct the defects, which were contained in malleable metal mesh. All three
      patients were fully weight-bearing by three months postoperatively. At two years
      follow-up, plain radiographs demonstrated maintenance of reduction and healing in
      all three cases.

PMID- 23547519
TI  - A modified custom-made triflanged acetabular reconstruction ring (MCTARR) for
      revision hip arthroplasty with severe acetabular defects.
AB  - The treatment of extensive acetabular bone loss and pelvic discontinuity in
      revision total hip arthroplasty remains challenging. We report our preliminary
      experience with the modified custom-made triflanged acetabular reconstruction
      ring (MCTARR) in the management of such situations. The MCTARR is a custom-made
      metal reinforcement ring with a trabecular surface to encourage bone ingrowth and
      a bulky trabecular metal augmentation to fill the acetabular defects, designed to
      achieve initial and long-term stability. A custom-made drilling jig is used to
      achieve optimal screw positioning. The clinical and radiological short-term
      follow-up (10-58 months) of our first six cases treated with this new technique
      show acceptable to good results. None of the reconstructions failed or had to be
      revised. Clinical results were satisfactory. Radiographs showed good screw
      positioning. The custom-made acetabular drilling jig and the reconstruction of
      the acetabulum with a titanium porous structure are of added value in the
      treatment of severe acetabular bone loss and pelvic discontinuity with custom
      made triflanged components.

PMID- 23547520
TI  - Diagnostic accuracy of ACL tears according to tear morphology.
AB  - This retrospective analysis of 182 consecutive patients who underwent anterior
      cruciate ligament (ACL) reconstruction aimed to assess the clinical examination
      under anaesthetic and the MRI diagnostic accuracy of arthroscopically-proven,
      complete ACL ruptures, depending on the morphology of the torn ligament. Patients
      were then assigned to Group 1 (ACL not reattached) or Group 2 (ACL re-attached
      abnormally). Of 104 patients (57.1%) in Group 2, 94 (51.7%) had an abnormal re
      attachment of the torn ACL to the posterior cruciate ligament (PCL). There was no
      significant difference between the groups on MRI reporting of a complete ACL tear
      (p = 0.123) and pivot shift test. On Lachman testing, more patients in Group 1
      had an increased laxity compared with Group 2 (p = 0.014); similarly, more
      patients in Group 1 had an absent endpoint compared with Group 2 (p = 0.008). An
      ACL-deficient knee with an abnormal re-attachment of the torn ligament appears to
      be more difficult to diagnose than if there has been no re-attachment.

PMID- 23547521
TI  - Recovery of knee mobility after a static or mobile spacer in total knee
      infection.
AB  - The purpose of the study was to compare the recovery of knee mobility after two
      stage revision of an infected total knee arthroplasty using a static or mobile
      spacer. At 12 months follow-up, none of the patients had a recurrent infection of
      their new prosthesis. Knee flexion was lower in the static spacer group at 3, 6
      and 12 months postoperatively. Patients that received a mobile spacer had a
      better and faster recovery of their knee function. The operation time of re
      implantation was shorter in the mobile spacer group than in the static spacer
      group. Our results suggest that patients treated with a mobile spacer have a
      faster recovery of the knee range of motion and a shorter operation time,
      including for the subsequent re-implantation of a prosthesis. Our results support
      the use of the mobile spacer in patients with an infected TKA that are treated
      with a two-stage revision of the prosthesis.

PMID- 23547522
TI  - Table-mounted ring retractor for consistent visualization in endoscopy-assisted
      anterior reconstruction of burst fractures of the thoracolumbar junction.
AB  - The authors tested an autoclavable external ring retractor, fixed to the
      operation table, for the endoscopic reconstruction of anterior column injuries of
      the thoracolumbar junction. It served as a retractor for the diaphragm, and
      offered a stable support for the scope and other instruments, making an assistant
      superfluous. Moreover, it allowed bimanual manipulation. Of course, the two
      dimensional image, provided by the scope, necessitated proper eye-hand
      coordination. Twenty-eight consecutive patients underwent either a monosegmental
      (n = 10) or a bisegmental (n = 18) anterior stabilization in the area Th11L1.
      Three portals were necessary, but an assistant was not needed. The overall (mean
      +/- SD) operating time was 196 +/- 56 min, the blood loss was 804 +/- 719 mL.
      Intraoperatively, one epidural bleeding and a single screw cut-out occurred. All
      complications were managed endoscopically. Postoperatively, evacuation of a
      haemothorax (n = 1) was necessary. In all patients, wounds and fractures healed
      uneventfully. The combination of the endoscopic technique and the retractor
      system was feasible, successful, safe, and time efficient. Moreover, it allowed
      for anterior instrumentation of thoracolumbar fractures by a single surgeon. It
      became the standard approach in the authors' department.

PMID- 23547523
TI  - Dynesys dynamic stabilization: less good outcome than lumbar fusion at 4-year
      follow-up.
AB  - Dynamic semirigid stabilization of the lumbar spine was introduced in 1994 in an
      attempt to overcome the drawbacks of fusion. It is supposed to preserve motion at
      the treated levels, while avoiding hypermobility and thus spondylosis at the
      adjacent levels. Although the early reports showed promising results, the long
      term effects are still debated. We retrospectively compared outcomes of Dynesys
      dynamic stabilization with those of the traditional fusion technique. Thirty-two
      patients who had undergone Dynesys between 2004 and 2006 (group 1) were compared
      to 32 patients who had been treated with fusion between 2005 and 2006 (group 2).
      VAS for back and leg pain, and ODI improved significantly in both groups (p <
      0.001). These scores were all better in the fusion group, and even significantly
      so as far as VAS for back pain was concerned (p = 0.014). Similarly, more
      patients were satisfied or very satisfied after fusion than after Dynesys: 87.5%
      versus 68.8% (p = 0.04). Interestingly, in the Dynesys group scatter plot graphs
      showed a positive correlation between older age and improvement in the two VAS
      scores and in ODI. Dynamic stabilization with Dynesys remains controversial.
      Older patients are relatively more satisfied about it, probably because of their
      low level of demands.

PMID- 23547524
TI  - Necrotising fasciitis: a series of seven cases.
AB  - Necrotising fasciitis of the extremities is a rapidly progressive, potentially
      life threatening soft tissue infection. Early diagnosis, aggressive surgical and
      critical care management is vital in preventing mortality. This series reports
      the clinical presentation, behaviour of inflammatory markers, histological,
      microbiological and radiological findings in seven cases, which presented to our
      orthopaedic unit over the last one year. Seven patients (4 male and 3 female)
      were included. Usual presentation was spreading erythema and pain. Duration of
      symptoms varied from 3 to 14 days. All except one case affected the lower limbs.
      The average Laboratory risk indicator for necrotising fasciitis (LRINEC) score on
      the day of presentation was 5. Imaging demonstrated subcutaneous oedema, fluid
      and air pockets in muscular planes. Group A beta haemolytic Streptococcus was the
      most common organism isolated from culture. Treatment modalities included
      antibiotics, immunoglobulins and surgical debridement. Four of the patients
      showed full remission. However, three (one with pre-existing carcinoma) of them
      succumbed to the condition.

PMID- 23547525
TI  - Cement technique for reducing post-operative bursitis after trochanteric
      fixation.
AB  - Post-operative trochanteric bursitis is a known complication secondary to the
      surgical approach in total hip arthroplasty. This phenomenon may be partially
      attributable to repetitive microtrauma generated when soft tissues rub against
      implanted hardware. Significant rates of post-operative trochanteric bursitis
      have been observed following procedures in which a trochanteric fixation device,
      such as a bolt-washer mechanism or a cable-grip/claw system, is used to secure
      the trochanteric fragment after trochanteric osteotomy. We present a simple
      technique for use with a bolt-washer system or grip plate in which trochanteric
      components are covered in bone wax followed by a layer of cement to decrease
      friction and to diminish the risk of post-operative bursitis.

PMID- 23547526
TI  - Bilateral insufficiency fracture of the femoral neck in a male patient with
      anorexia nervosa.
AB  - Anorexia nervosa is a risk factor for secondary osteoporosis. Anorexia nervosa
      related metabolic disturbances lead to disminished bone resistance and increased
      risk of fractures. We report a case of bilateral femoral neck fracture as the
      first symptom of anorexia nervosa in a male patient.

PMID- 23547527
TI  - Primary total hip arthroplasty with a retained intramedullary femoral nail.
AB  - Retained intramedullary femoral nails can pose a problem for the implantation of
      the femoral component during total hip arthoplasty (THA) and they must often be
      removed. A patient with a retained Kuntscher femoral nail implanted 47 years
      previously presented in our outpatient clinic for a THA. Since removal of the
      nail was impossible without severe damage to the femur, we chose to perform an
      extended trochanteric osteotomy, to cut the proximal part of the nail and to
      implant a cemented short stem with its tip in the hollow end of the nail.

PMID- 23547528
TI  - Single-level transforaminal interbody fusion for traumatic lumbosacral fracture
      dislocation: a case report.
AB  - L5S1 fracture-dislocations are rare three-column injuries. The infrequency of
      this injury has led to a lack of a universally accepted treatment strategy.
      Transforaminal lumbar interbody fusion (TLIF) has been shown to be an effective
      approach for interbody fusion in degenerative indications, but has not been
      previously reported in the operative management of traumatic lumbosacral
      dislocation. The authors report a case of traumatic L5S1 fracture-dislocation in
      a 30-year-old male, presenting with a right-sided L5 neurologic deficit,
      following a street sweeper accident. Imaging revealed an L5S1 fracture
      dislocation with fracture of the S1 body. Open reduction with TLIF and L5S1
      posterolateral instrumented fusion was carried out within 24 hours of injury.
      Excellent reduction was obtained, and maintained at long-term follow-up, with
      complete resolution of pain and neurologic deficit. In this patient, L5S1
      fracture-dislocation was treated successfully, with an excellent outcome, with a
      single level TLIF and instrumented posterolateral fusion at L5S1.

PMID- 23547529
TI  - Release of polyphenolic drugs from dynamically bonded layer-by-layer films.
AB  - Layer-by-layer (LbL) assembled films have been exploited for surface-mediated
      drug delivery. The drugs loaded in the films were usually released via diffusion
      or the degradation of one of the film components. Here we demonstrate that drug
      release can also be achieved by exploiting the dynamic nature of hydrogen-bonded
      LbL films. The films were fabricated from tannic acid (TA), a model polyphenolic
      drug, and poly(vinyl pyrrolidone) (PVPON). The driving force for the film buildup
      is the hydrogen bonding between the two components, which was confirmed by
      Fourier transform infrared (FTIR) spectra. The film growth is linear, and the
      growth rate of the film decreases with increasing assembly temperature. Because
      of the reversible/dynamic nature of hydrogen bonding, when soaked in aqueous
      solutions, the PVPON/TA films disassemble gradually and thus release TA to the
      media. The release rate of TA increases with increasing pH and temperature but
      decreases with increasing ionic strength. Scanning electron microscopy (SEM)
      studies on the surface morphology of the film during TA release reveal that the
      film surface becomes smoother and then rougher again because of the dewetting of
      the film. The released TA can scavenge ABTS(+*) cation radicals, indicating it
      retains its antioxidant activity, a major biological activity of polyphenols.

PMID- 23547530
TI  - Self-assembled proteins and peptides for regenerative medicine.

PMID- 23547531
TI  - Using compound-specific isotope analysis to assess biodegradation of
      nitroaromatic explosives in the subsurface.
AB  - Assessing the fate of nitroaromatic explosives in the subsurface is challenging
      because contaminants are present in different phases (e.g., bound to soil or
      sediment matrix or as solid-phase residues) and transformation takes place via
      several potentially competing pathways over time-scales of decades. We developed
      a procedure for compound-specific analysis of stable C, N, and H isotopes in
      nitroaromatic compounds (NACs) and characterized biodegradation of 2,4,6
      trinitrotoluene (TNT) and two dinitrotoluene isomers (2,4-DNT and 2,6-DNT) in
      subsurface material of a contaminated site. The type and relative contribution of
      reductive and oxidative pathways to the degradation of the three contaminants was
      inferred from the combined evaluation of C, N, and H isotope fractionation.
      Indicative trends of Deltadelta(15)N vs Deltadelta(13)C and Deltadelta(2)H vs
      Deltadelta(13)C were obtained from laboratory model systems for biodegradation
      pathways initiated via (i) dioxygenation, (ii) reduction, and (iii) CH3-group
      oxidation. The combined evaluation of NAC isotope fractionation in subsurface
      materials and in laboratory experiments suggests that in the field, 86-89% of 2,4
      DNT transformation was due to dioxygenation while TNT was mostly reduced and 2,6
      DNT reacted via a combination of reduction and CH3-group oxidation. Based on
      historic information on site operation, our data imply biodegradation of 2,4-DNT
      with half-lives of up to 9-17 years compared to 18-34 years for cometabolic
      transformation of TNT and 2,6-DNT. 

PMID- 23547532
TI  - Correction of hyperpigmented palmar grafts with full-thickness skin grafts from
      the lateral aspect of the foot.
AB  - The palmar surface of the hand possesses special features when compared with the
      hair-bearing parts of the body. The same quality of skin has to be used in
      reconstruction of the palmar skin defects to restore normal function. The lateral
      aspect of the foot has similar features with the palmar region histologically and
      can be used for palmar reconstruction. Seventeen patients who had
      hyperpigmentation after skin graft in the palmar region were treated. Scar
      contracture was combined in seven patients. The hyperpigmented grafts were
      excised and then the defects were full-thickness skin grafted from the lateral
      aspect of the foot. The mean follow-up period was 13.7 (4-22) months. Engraftment
      was successful in 16 patients, but one failed due to haematoma. The colour of the
      graft was initially reddish, and then became similar to the palmar area. The
      donor site healed without any problem within 3 weeks. At follow-up these grafts
      had good colour and texture match with adjacent palmar skin. There was no
      hyperpigmentation. Minimal marginal scarring and scar hypertrophy occurred in
      four patients (24%). The skin of the lateral aspect of the foot is a good choice
      for palmar skin defects, because of the similarities in their characteristics.
      Results are acceptable in terms of minimal recurrence of scar contracture, no
      hyperpigmentation, adequate colour and texture match, and minimal marginal
      scarring and scar hypertrophy.

PMID- 23547533
TI  - Two-stage free latissimus dorsi flap: a safe strategy for reconstruction of large
      defects of the abdominal wall.
AB  - We report a case of full abdominal wall reconstruction after resection of a
      dermatofibrosarcoma protuberans. The treatment comprised wide resection with a 5
      cm peripheral margin and deep resection to a disease-free anatomical structure.
      The reconstruction was done in two-stages with a free latissimus dorsi flap.

PMID- 23547535
TI  - Anatomical closure technique of the nasal floor for patients with complete
      unilateral cleft lip and palate.
AB  - We describe a new technique for the reconstruction of the nasal floor at the same
      time as cheiloplasty in patients with complete unilateral cleft lip and palate.
      We operated on patients aged between 3 and 36 months in public secondary and
      tertiary level institutions. None of these patients had had a previous operation
      for the correction of the cleft lip or palate. The operation required the design
      of two mucous flaps, one lateral and one medial to the defect, to reposition the
      tissues anatomically and repair the congenital deficiency. Three hundred and
      fifty-eight patients have been treated using this technique, most of whom (n =
      233, 65%) were boys, and 288 (80%) presented with a right complete unilateral
      cleft. Postoperative evaluation showed that 22 patients (6%) had asymmetry of the
      nasal base equal to or less than 1 mm, 18 (5%) had nasovestibular fistulas, and 5
      (1%) required revision. We conclude that this technique greatly reduces the
      number of asymmetrical nasal floors and the incidence of nasovestibular fistulas.

PMID- 23547534
TI  - Assessment of the 18-month permanence of onlay tip cartilage grafts following
      rhinoplasty.
AB  - Augmentation rhinoplasty requires addition of materials of various natures to
      reshape the nasal pyramid. Onlay tip grafts are single or multilayered grafts
      placed horizontally over the alar domes. The aim of the present study was to
      assess the 18-month permanence of onlay septal cartilage grafts. Twenty-eight
      patients underwent rhinoplasty with onlay tip cartilage graft, between June 2008
      and November 2008 at the Campus Bio-Medico University in Rome, Italy. They were
      reviewed and photographed 6 months and 18 months postoperatively. Comparison of 6
      month and 18-month postoperative pictures was performed with Adobe Photoshop CS.
      Measurements on pictures were taken with AutoCAD. Comparison of photographs
      showed no visible difference in nasal tip projection. Comparison of the
      measurements of tip projection showed a mean reduction of 0.06 mm (0.19%).
      Considerable stability of nasal tip projection after rhinoplasty with onlay tip
      grafts was observed postoperatively. Comparison of standardised digital
      photographs is a valid procedure to assess contour alterations of various
      anatomical structures after plastic surgery.

PMID- 23547536
TI  - Long-term effects of preserving or splitting the carpal ligament in carpal tunnel
      operation.
AB  - Carpal tunnel syndrome is treated very successfully by surgical release of the
      flexor retinaculum. However, in some patients, all symptoms are not resolved.
      Weakness in grip strength and pain in the thenar and hypothenar areas
      corresponding to the end of the transverse ligament after its complete section
      have been described as common complications of classical neurolysis of the median
      nerve. This study presents here the long-term results of decompression operation
      of the median nerve at the wrist, conserving the transverse ligament, as well as
      its comparison with the classical open neurolysis with a complete section of the
      ligament. This is an analysis of a retrospective cohort of 114 patients, who were
      operated on for carpal tunnel syndrome. A clinical, electromyographic, and
      dynamometric evaluation of the patients studied was carried out in a comparative
      analysis of the surgical techniques used (flexor retinaculum lengthening
      according to the Simonetta technique and classical open neurolysis of the median
      nerve), in a period of 10 years after the operation. The ligamentoplasty
      technique, in the long-term, contributes to better results of manual force, with
      a smaller resolution of tingling sensations than the neurolysis with complete
      section of the transverse ligament. For those patients who do not present a
      severe clinical or electromyographic syndrome, and in addition require manual
      effort for their daily activities, the technique of ligamentoplasty, according to
      Simonetta, is a surgical option to be taken into account.

PMID- 23547537
TI  - A comparison of digital morphometry and clinical measurements of ears.
AB  - Clinical measurements are necessary in many routine follow-ups and scientific
      evaluations, but the accuracy of these measurements is seldom challenged. The
      size of the reconstructed ear is one important parameter in the follow-up
      regarding patients operated on due to microtia. With the introduction of digital
      morphometry one was obliged to evaluate its accuracy in comparison to its
      analogue equivalents. In a first series of measurements the ears of 30 persons
      were assessed using digital morphometry, compass and ruler, and calliper to test
      the accuracy of these methods. In a second series of measurements, 10 patients
      with reconstructed unilateral microtia were assessed with digital morphometry to
      test the inter-individual variation of this method. The accuracy of digital
      morphometry was of the same magnitude as the manual methods. When the inter
      individual variation of accuracy was assessed in digital morphometry it was found
      that random error differed from person to person. In scientific settings, for
      instance when evaluating possible growth of the cartilage framework, the specific
      individual accuracy must therefore be taken into account in order to draw safe
      conclusions.

PMID- 23547538
TI  - Blood flow dynamics in reconstructed auricles.
AB  - Ear reconstruction with autologous rib cartilage is performed in stages.
      Restitution of blood flow between the separate stages is crucial to obtain a good
      result. Laser Doppler perfusion imaging (LDPI) and local temperature were
      measured in reconstructed and normal ears in response to indirect heating. Ten
      persons who had had a unilateral ear reconstruction were included in the study.
      At a minimum, 157 days had passed since the last operation. LDPI showed no
      difference in blood flow between the reconstructed ear and the normal ear,
      neither before nor after indirect heating. The upper part of the normal ear was
      slightly cooler than the corresponding part in the reconstructed ear. Indirect
      heating caused an increase of LDPI-values and temperatures in the upper, middle,
      and lower part of the ear both in the reconstructed ear and the normal one. Skin
      blood flow recovers after 3-stage ear reconstruction and shows normal dynamic
      response upon indirect heating.

PMID- 23547539
TI  - External Mustarde suture technique in otoplasty revisited: a report of 82 cases.
AB  - In otoplasty surgery the antihelical fold is frequently created using Mustarde
      sutures. When using the Mustarde suture technique it is important to insert the
      needle through the cartilage at right angles. This technical objective is easily
      achieved with an external Mustarde suture technique. A review of 82 patients who
      underwent otoplasty between 2005 and 2011 was conducted. All patients underwent
      external Mustarde suture otoplasty without conchal cartilage resection. The
      cartilage had been softened by rasping and conchomastoidal sutures had been used
      to correct conchal excess if necessary. In one patient, a secondary revision was
      performed for inadequate superior pole correction. In three patients sutures were
      visible after 1 year postoperatively and the sutures were removed under local
      anaesthesia without any recurrence. In one patient blister formation occurred due
      to inaccurate packing, but healed without any problem in a few days. No other
      complications, such as bowstringing of the internal sutures, haematoma, or
      infection, were observed. The patients expressed a high degree of satisfaction
      with their results. The risk of technical error is minimal. It is easy to perform
      and not time-consuming. Due to these advantages, this method is a reliable
      technique in otoplasty.

PMID- 23547540
TI  - Immediate two-stage tissue expander breast reconstruction compared with one-stage
      permanent implant breast reconstruction: a multi-institutional comparison of
      short-term complications.
AB  - Prosthesis-based techniques are the predominant form of breast reconstruction
      worldwide, with two-stage tissue expander procedures being the most popular. In
      the past decade, there has been increasing interest in performing single-stage
      implant reconstruction immediately following mastectomy as an attempt to simplify
      the reconstructive course and improve psychosocial morbidity. However, there is a
      paucity of large-scale, multi-institutional data comparing the outcomes of these
      two reconstructive strategies. Patients who underwent immediate tissue expander
      or implant reconstruction following mastectomy from 2006-2010 were identified
      using standardised operation codes. Demographic information for patients, 30-day
      outcomes, and adverse events for each type of reconstruction were analysed and
      compared between groups. A total of 10,561 patients underwent immediate breast
      reconstruction. There were 9033 patients who underwent tissue expander placement
      (2752 bilateral), and 1528 patients who underwent immediate implant placement
      (485 bilateral). Patients who had implant placement demonstrated increased rates
      of overall complications (6.8% compared with 5.4%, p = 0.02) and prosthesis
      failure (1.4% compared with 0.8%, p = 0.04). There was no difference in the rate
      of any surgical site infections (3.9% compared with 3.4%, p = 0.39), reoperation
      (7.5% compared with 6.9%, p = 0.40), or major medical complications (1.8%
      compared with 1.6%, p = 0.57). Both immediate one-stage, direct-to-implant, and
      two-stage tissue expander reconstructions result in low rates of morbidity. One
      stage reconstruction suggests a slightly higher complication rate related to
      prosthesis failure.

PMID- 23547541
TI  - Glomus tumours in the long finger and in the thumb of a young patient with
      neurofibromatosis-1 (Nf-1).
AB  - Glomus tumours are rare in adults, and such tumours may be associated with
      neurofibromatosis-1 (Nf-1). Here we describe successful treatment of two glomus
      tumours initially in the long finger and, one year later, in the thumb in a 17
      year young girl with Nf-1.

PMID- 23547542
TI  - Cyclosporin A reduces matrix metalloproteinases and collagen expression in dermal
      fibroblasts from regenerative FOXN1 deficient (nude) mice.
AB  - BACKGROUND: Cyclosporin A (CsA), an immunosuppressive agent modifies the wound
      healing process through an influence on extracellular matrix metabolism. We have
      compared the effects of CsA on dermal fibroblasts from nude (FOXN1 deficient)
      mice, a genetic model of skin scarless healing, and from control (C57BL/6 J (B6)
      mice to evaluate metabolic pathways that appear to have important roles in the
      process of scarless healing/regeneration. RESULTS: High levels of matrix
      metalloproteinases (MMPs) and collagen III expression in dermal fibroblasts from
      nude (regenerative) mice were down-regulated by CsA treatment to the levels
      observed in dermal fibroblasts from B6 (non-regenerative) mice. In contrast,
      dermal fibroblasts from control mice respond to CsA treatment with a minor
      reduction of Mmps mRNA and 2.5-fold increase expression of collagen I mRNA. An in
      vitro migratory assay revealed that CsA treatment profoundly delayed the
      migratory behavior of dermal fibroblasts from both nude and control mice.
      CONCLUSION: The data suggest that by alternation of the accumulation of
      extracellular matrix components CsA treatment stimulates the transition from a
      scarless to a scar healing.

PMID- 23547543
TI  - Absence of abdominal pain does not rule out diagnosis of IBS.

PMID- 23547546
TI  - Physical training for patients with asthma.

PMID- 23547547
TI  - Vitamin D supplementation for women during pregnancy.

PMID- 23547548
TI  - The potential adverse health effects of energy drinks.

PMID- 23547549
TI  - Reducing the risk of adverse drug events in older adults.
AB  - Adverse drug events occur in 15 percent or more of older patients presenting to
      offices, hospitals, and extended care facilities. These events are potentially
      preventable up to 50 percent of the time. Common serious manifestations include
      falls, orthostatic hypotension, heart failure, and delirium. The most common
      causes of death are gastrointestinal or intracranial bleeding and renal failure.
      Antithrombotic and antidiabetic medications, diuretics, and nonsteroidal anti
      inflammatory drugs cause most of the preventable hospital admissions due to
      adverse drug events. Strategies to reduce the risk of adverse drug events include
      discontinuing medications, prescribing new medications sparingly, reducing the
      number of prescribers, and frequently reconciling medications. The Beers, STOPP
      (screening tool of older persons' potentially inappropriate prescriptions), and
      START (screening tool to alert doctors to right treatment) criteria can help
      identify medications causing adverse drug events. Not all potentially
      inappropriate medications can be avoided. Clinicians should involve patients in
      shared decision making and individualize prescribing decisions based on medical,
      functional, and social conditions; quality of life; and prognosis.

PMID- 23547550
TI  - Diabetic ketoacidosis: evaluation and treatment.
AB  - Diabetic ketoacidosis is characterized by a serum glucose level greater than 250
      mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L,
      an elevated serum ketone level, and dehydration. Insulin deficiency is the main
      precipitating factor. Diabetic ketoacidosis can occur in persons of all ages,
      with 14 percent of cases occurring in persons older than 70 years, 23 percent in
      persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and
      36 percent in persons younger than 30 years. The case fatality rate is 1 to 5
      percent. About one-third of all cases are in persons without a history of
      diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent),
      weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting
      (46 percent), preceding febrile illness (40 percent), abdominal pain (32
      percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitrogen,
      creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood
      count; urinalysis; electrocardiography; and calculation of anion gap and osmolar
      gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic
      state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and
      can assist in diagnosing comorbid conditions. Appropriate treatment includes
      administering intravenous fluids and insulin, and monitoring glucose and
      electrolyte levels. Cerebral edema is a rare but severe complication that occurs
      predominantly in children. Physicians should recognize the signs of diabetic
      ketoacidosis for prompt diagnosis, and identify early symptoms to prevent it.
      Patient education should include information on how to adjust insulin during
      times of illness and how to monitor glucose and ketone levels, as well as
      information on the importance of medication compliance.

PMID- 23547551
TI  - Identification and treatment of amblyopia.
AB  - Amblyopia is the leading cause of vision loss in children. It is treatable if
      diagnosed early, making identification of affected children critical. The
      American Association for Pediatric Ophthalmology and Strabismus and the American
      Academy of Pediatrics recommend that clinicians routinely perform age-appropriate
      vision chart testing, red reflex testing, and examination for signs of
      strabismus. The U.S. Preventive Services Task Force recommends vision screening
      for all children at least once between three and five years of age to detect the
      presence of amblyopia or its risk factors. Photoscreening may be a useful adjunct
      to traditional vision screening, but there is limited evidence that it improves
      visual outcomes. Treatments for amblyopia include patching, atropine eye drops,
      and optical penalization of the nonamblyopic eye. In children with moderate
      amblyopia, patching for two hours daily is as effective as patching for six hours
      daily, and daily atropine is as effective as daily patching. Children older than
      seven years may still benefit from patching or atropine, particularly if they
      have not previously received amblyopia treatment. Amblyopia recurs in 25 percent
      of children after patching is discontinued. Tapering the amount of time a patch
      is worn each day at the end of treatment reduces the risk of recurrence.

PMID- 23547552
TI  - Analgesics for osteoarthritis.

PMID- 23547553
TI  - Caring for older patients who have significant hearing loss.

PMID- 23547554
TI  - Spontaneous hematomas.

PMID- 23547557
TI  - Patient information. Adverse drug events in older adults: how to avoid them.

PMID- 23547558
TI  - Phase I study of OM-174, a lipid A analogue, with assessment of immunological
      response, in patients with refractory solid tumors.
AB  - BACKGROUND: Lipids A, the lipophilic partial structure of lipopolysaccharides,
      induce regression of several tumor types in animal models. Rather than exerting
      direct cytotoxic effect, these compounds trigger the immune system which in turn
      stimulates secretion of cytokines, and activates the inducible nitric oxide
      synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of
      lipid A with dual action on Toll-like receptors 2 and 4. In an experimental model
      of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of
      syngeneic PROb colon cancer cells, it induced a complete regression of tumors.
      The present phase I trial was conducted to determine the maximum tolerated dose,
      the recommended phase II dose and biological response associated with OM-174
      administered as intravenous infusion. METHODS: Patients received OM-174 twice
      weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 MUg/m(2).
      Blood samples for pharmacokinetic analysis and cytokine dosages were collected.
      NK cells activity and Toll-like receptors 4 polymorphism analysis were also
      performed. RESULTS: Seventeen patients were included. The highest dose
      administered was 1000 MUg/m(2) repeated in 15 injections. The most common
      toxicities were a chills, fever, nausea/vomiting, diarrhea, fatigue and headache.
      No patient experienced haematological side effects. As no dose limiting toxicity
      was observed, despite a grade 3 respiratory complication, the maximal tolerated
      dose and recommended dose were not established. Three patients exhibited disease
      stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174
      was characterized by a low distribution volume and clearance. Analysis of TLR 4
      polymorphysm showed that most (16/17) patients carried the wild type alleles. A
      progressive increase in NK cell number and activity was observed only in patients
      receiving 1000 MUg/m(2) of OM-174. A peak of IL-8 and IL-10 concentrations were
      observed after each OM-174 injection. Peaks of TNF-alpha and IL-6 concentrations
      were detected after the first infusion and decreased progressively suggesting
      tolerance. CONCLUSION: OM-174 therapy was well tolerated at biologically active
      concentrations. Whereas the recommended dose was not determined, further studies
      are planned in combination with chemotherapy as animal models suggest a strong
      synergistic antitumor effect. TRIAL REGISTRATION: NCT01800812 (ClinicalTrials.gov
      Identifier).

PMID- 23547560
TI  - Spin transitions in Fe(II) metallogrids modulated by substituents, counteranions,
      and solvents.
AB  - Two bis(tridentate) Schiff base ligands H2L(x) were used to construct three 2*2
      grid-type tetranuclear Fe(II) complexes 1-3 to obtain polynuclear spin-crossover
      materials. Magnetic susceptibility measurements show that the spin states of the
      complexes are related to the substituents of H2L(x), and that spin transition
      occurs only in complexes 1 and 2, which are derived from a bulky ligand, whereas
      complex 3 is diamagnetic. The transition temperatures of complexes 1 and 2 are
      close to room temperature and are dependent on counteranions. The spin transition
      of complex 1 can be reversibly tuned by the dehydration and hydration process.

PMID- 23547559
TI  - Modulation of the cortical silent period elicited by single- and paired-pulse
      transcranial magnetic stimulation.
AB  - BACKGROUND: The cortical silent period (CSP) elicited by transcranial magnetic
      stimulation (TMS) is affected by changes in TMS intensity. Some studies have
      shown that CSP is shortened or prolonged by short-interval intracortical
      inhibition (SICI) and intracortical facilitation (ICF), Those studies, however,
      used different TMS intensities to adjust the amplitude of the motor evoked
      potential (MEP). Therefore, it is unclear whether changes in CSP duration are
      induced by changes in TMS intensities or by SICI and ICF. The purpose of this
      study was to confirm the effects of muscle contractions and stimulus intensities
      on MEP amplitude and the duration of CSP induced by single-pulse TMS and to
      clarify the effects of SICI and ICF on CSP duration.MEP evoked by TMS was
      detected from the right first dorsal interosseous muscle in 15 healthy subjects.
      First, MEP and CSP were induced by single-pulse TMS with an intensity of 100%
      active motor threshold (AMT) at four muscle contraction levels [10%, 30%, 50%,
      and 70% electromyogram (EMG)]. Next, MEP and CSP were induced by seven TMS
      intensities (100%, 110%, 120%, 130%, 140%, 150%, and 160% AMT) during muscle
      contraction of 10% EMG. Finally, SICI and ICF were recorded at the four muscle
      contraction levels (0%, 10%, 30%, and 50% EMG). RESULTS: MEP amplitudes increased
      with increases in muscle contraction and stimulus intensity. However, CSP
      duration did not differ at different muscle contraction levels and was prolonged
      with increases in stimulus intensity. CSP was shortened with SICI compared with
      CSP induced by single-pulse TMS and with ICF at all muscle contraction levels,
      whereas CSP duration was not significantly changed with ICF. CONCLUSIONS: We
      confirmed that CSP duration is affected by TMS intensity but not by the muscle
      contraction level. This study demonstrated that CSP is shortened with SICI, but
      it is not altered with ICF. These results indicate that after SICI, CSP duration
      is affected by the activity of inhibitory intermediate neurons that are activated
      by the conditioning SICI stimulus.

PMID- 23547561
TI  - Kruppel-like factor 6 (KLF6) promotes cell proliferation in skeletal myoblasts in
      response to TGFbeta/Smad3 signaling.
AB  - BACKGROUND: Kruppel-like factor 6 (KLF6) has been recently identified as a MEF2D
      target gene involved in neuronal cell survival. In addition, KLF6 and TGFbeta
      have been shown to regulate each other's expression in non-myogenic cell types.
      Since MEF2D and TGFbeta also fulfill crucial roles in skeletal myogenesis, we
      wanted to identify whether KLF6 functions in a myogenic context. METHODS: KLF6
      protein expression levels and promoter activity were analyzed using standard
      cellular and molecular techniques in cell culture. RESULTS: We found that KLF6
      and MEF2D are co-localized in the nuclei of mononucleated but not multinucleated
      myogenic cells and, that the MEF2 cis element is a key component of the KLF6
      promoter region. In addition, TGFbeta potently enhanced KLF6 protein levels and
      this effect was repressed by pharmacological inhibition of Smad3. Interestingly,
      pharmacological inhibition of MEK/ERK (1/2) signaling resulted in re-activation
      of the differentiation program in myoblasts treated with TGFbeta, which is
      ordinarily repressed by TGFbeta treatment. Conversely, MEK/ERK (1/2) inhibition
      had no effect on TGFbeta-induced KLF6 expression whereas Smad3 inhibition negated
      this effect, together supporting the existence of two separable arms of TGFbeta
      signaling in myogenic cells. Loss of function analysis using siRNA-mediated KLF6
      depletion resulted in enhanced myogenic differentiation whereas TGFbeta
      stimulation of myoblast proliferation was reduced in KLF6 depleted cells.
      CONCLUSIONS: Collectively these data implicate KLF6 in myoblast proliferation and
      survival in response to TGFbeta with consequences for our understanding of muscle
      development and a variety of muscle pathologies.

PMID- 23547562
TI  - Alcohol ingestion disrupts alveolar epithelial barrier function by activation of
      macrophage-derived transforming growth factor beta1.
AB  - BACKGROUND: Chronic alcohol abuse causes oxidative stress and impairs alveolar
      epithelial barrier integrity, thereby rendering the lung susceptible to acute
      edematous injury. Experimentally, alcohol-induced oxidative stress increases the
      expression of transforming growth factor beta1 (TGFbeta1) in the lung; however,
      we do not know the precise contribution of various alveolar cells in this
      process. In the present study, we focused on cell-cell interactions between
      alveolar macrophages and epithelial cells and the potential mechanisms by which
      TGFbeta1 may become activated in the alveolar space of the alcoholic lung.
      METHODS: Primary alveolar macrophages and epithelial cells were isolated from
      control- and alcohol-fed Sprague-Dawley rats. Expression of TGFbeta1 and the
      epithelial integrin alphavbeta6 were examined by real time PCR and either
      immunocytochemistry or flow cytometry. Alveolar epithelial cells were cultured on
      transwell supports in the presence of macrophage cell lysate from control- or
      alcohol-fed rats or in the presence of viable macrophages +/- alcohol. Epithelial
      barrier function was assessed by transepithelial resistance (TER) and
      paracellular flux of Texas Red dextran. RESULTS: TGFbeta1 expression was
      increased in alveolar macrophages from alcohol-fed rats, and TGFbeta1 protein was
      predominantly membrane-bound. Importantly, alveolar macrophage cellular lysate
      from alcohol-fed rats decreased TER and increased paracellular dextran flux in
      primary alveolar epithelial cell monolayers as compared to the lysates from
      control-fed rats. Alcohol-induced epithelial barrier dysfunction was prevented by
      anti-TGFbeta1 antibody treatment, indicating the presence of bioactive TGFbeta1
      in the macrophage lysate. In addition, co-culturing macrophages and epithelial
      cells in the presence of alcohol decreased epithelial barrier function, which
      also was prevented by anti-TGFbeta1 and anti-alphavbeta6 treatment. In parallel,
      chronic alcohol ingestion in vivo, or direct treatment with active TGFbeta1 in
      vitro, increased the expression of alphavbeta6 integrin, which is known to
      activate TGFbeta1, in alveolar epithelial cells. CONCLUSIONS: Taken together,
      these data suggest that interactions between alveolar epithelial cells and
      macrophages contribute to the alcohol-mediated disruption of epithelial barrier
      function via the expression and activation of TGFbeta1 at points of cell-cell
      contact.

PMID- 23547563
TI  - Autoinflammatory gene polymorphisms and susceptibility to UK juvenile idiopathic
      arthritis.
AB  - BACKGROUND: To investigate the autoinflammatory hereditary periodic fever
      syndrome genes MVK and TNFRSF1A, and the NLRP1 and IL1 genes, for association
      with juvenile idiopathic arthritis (JIA). METHODS: For MVK, TNFRSF1A and NLRP1
      pair-wise tagging SNPs across each gene were selected and for IL1A SNPs from a
      prior meta-analysis were included. 1054 UK Caucasian JIA patients were genotyped
      by Sequenom iPlex MassARRAY and allele and genotype frequencies compared with
      5380 unrelated healthy UK Caucasian controls. RESULTS: Four SNPs were
      significantly associated with UK JIA: rs2071374 within intron 4 of IL1A
      (ptrend=0.006), rs2228576 3' of TNFRSF1A (ptrend=0.009) and 2 SNPs, rs11836136
      and rs7957619, within MVK (ptrend=0.006, ptrend=0.005 respectively). In all cases
      the association appeared to be driven by the systemic-onset JIA (SoJIA) subtype.
      Genotype data for the two MVK SNPs was available in a validation cohort of 814
      JIA (oligoarticular and RF negative polyarticular) cases and 3058 controls from
      the US. Replication was not confirmed, however, further suggesting that this
      association is specific to SoJIA. CONCLUSIONS: These findings extend the
      observations of the relevance of studying monogenic loci as candidates for
      complex diseases. We provide novel evidence of association of MVK and TNFRSF1A
      with UK JIA, specifically driven by association with SoJIA and further confirm
      that the IL1A SNP association with SoJIA is subtype specific. Replication is
      required in independent cohorts.

PMID- 23547566
TI  - Children's fruit and vegetable intake, programme evaluation.

PMID- 23547565
TI  - Biobanking research on oncological residual material: a framework between the
      rights of the individual and the interest of society.
AB  - BACKGROUND: The tissue biobanking of specific biological residual materials,
      which constitutes a useful resource for medical/scientific research, has raised
      some ethical issues, such as the need to define which kind of consent is
      applicable for biological residual materials biobanks. DISCUSSION: Biobank
      research cannot be conducted without considering arguments for obtaining the
      donors' consent: in this paper we discuss to what extent consent in biobank
      research on oncological residual materials has to be required, and what type of
      consent would be appropriate in this context, considering the ethical principles
      of donation, solidarity, protection of the donors' rights and the requirements of
      scientific progress. Regarding the relationship between informed consent and
      tissue collection, storage and research, we have focused on two possible choices
      related to the treatment of data and samples in the biobank: irreversible and
      reversible anonymization of the samples, distinguishing between biobank research
      on residual materials for which obtaining consent is necessary and justified, and
      biobank research for which it is not. The procedures involve different approaches
      and possible solutions that we will seek to define. The consent for clinical
      research reported in the Helsinki Declaration regards research involving human
      beings and for this reason it is subordinate to specific and detailed information
      on the research projects. SUMMARY: An important ethical aspect in regard to the
      role of Biobanks is encouraging sample donation. For donors, seeing human samples
      being kept rather than discarded, and seeing them become useful for research
      highlights the importance of the human body and improves the attitude towards
      donation. This process might also facilitate the giving of informed consent more
      willingly, and with greater trust.

PMID- 23547567
TI  - Increased detection of invasive enteropathogenic bacteria in pre-incubated blood
      culture materials by real-time PCR in comparison with automated incubation in Sub
      Saharan Africa.
AB  - BACKGROUND: Invasive enteropathogenic bacteria can cause systemic infections.
      Data from studies with PCR detection suggest, at least for Salmonella enterica,
      that blood culture may lead to underestimation in the tropics. Corresponding data
      are lacking for other invasive enteropathogenic bacteria. We compared classical
      blood culture and molecular methods for the diagnosis of blood infections.
      METHODS: A real-time multiplex PCR for Salmonella spp., Shigella spp./entero-
      invasive Escherichia coli (EIEC), Yersinia spp., and Campylobacter jejuni was
      applied to 2321 retained blood culture samples from Ghanaian patients, after
      enrichment by automated culture. RESULTS: PCR detected Salmonella DNA in 56 out
      of 58 pre-incubated Ghanaian blood cultures with growth of S. enterica. In 2
      samples molecular diagnosis was only possible after 1:10 dilution. Twenty-two
      samples negative by blood culture and 1 positive with Micrococcus spp. were PCR
      positive for Salmonella spp. In addition, 3 Shigella spp./EIEC, 2 Yersinia spp.,
      and 1 C. jejuni were detected by PCR but not by culture growth. CONCLUSIONS: Real
      time PCR was more sensitive in identifying invasive enteropathogenic bacteria
      than automated blood culture, which is hampered by a lack of evidence-based
      standardization of pre-analytic conditions in the tropics. Primary agar culture
      and Gram-staining prior to automated blood culture is advisable in cases where
      transportation times are long.

PMID- 23547564
TI  - A pilot study of the effect of spironolactone therapy on exercise capacity and
      endothelial dysfunction in pulmonary arterial hypertension: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Pulmonary arterial hypertension is a rare disorder associated with
      poor survival. Endothelial dysfunction plays a central role in the pathogenesis
      and progression of pulmonary arterial hypertension. Inflammation appears to drive
      this dysfunctional endothelial phenotype, propagating cycles of injury and repair
      in genetically susceptible patients with idiopathic and disease-associated
      pulmonary arterial hypertension. Therapy targeting pulmonary vascular
      inflammation to interrupt cycles of injury and repair and thereby delay or
      prevent right ventricular failure and death has not been tested. Spironolactone,
      a mineralocorticoid and androgen receptor antagonist, has been shown to improve
      endothelial function and reduce inflammation. Current management of patients with
      pulmonary arterial hypertension and symptoms of right heart failure includes use
      of mineralocorticoid receptor antagonists for their diuretic and natriuretic
      effects. We hypothesize that initiating spironolactone therapy at an earlier
      stage of disease in patients with pulmonary arterial hypertension could provide
      additional benefits through anti-inflammatory effects and improvements in
      pulmonary vascular function. METHODS/DESIGN: Seventy patients with pulmonary
      arterial hypertension without clinical evidence of right ventricular failure will
      be enrolled in a randomized, double-blinded, placebo-controlled trial to
      investigate the effect of early treatment with spironolactone on exercise
      capacity, clinical worsening and vascular inflammation in vivo. Our primary
      endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and
      the incidence of clinical worsening in the spironolactone group compared to
      placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to
      detect an effect size (group mean difference divided by standard deviation) of
      0.9 for the difference in the change of 6-minute walk distance from baseline
      between the two groups. Secondary endpoints include the effect of spironolactone
      on the change in placebo-corrected maximal oxygen consumption; plasma markers of
      vascular inflammation and peripheral blood mononuclear cell gene expression
      profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone
      system activation and sex hormone metabolism; and right ventricular structure and
      function using echocardiography and novel high-resolution magnetic resonance
      imaging-based techniques. Safety and tolerability of spironolactone will be
      assessed with periodic monitoring for hyperkalemia and renal insufficiency as
      well as the incidence of drug discontinuation for untoward effects. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01712620.

PMID- 23547569
TI  - Treatment of acute cystitis in Hungary: comparison with national guidelines and
      with disease-specific quality indicators.
AB  - BACKGROUND: The aim of this study was to compare Hungarian antibiotic use in
      acute cystitis with the internationally developed disease-specific quality
      indicators and with the national guidelines. METHODS: The aggregated national
      level data on systemic antibiotic use was purchased from the National Health Fund
      Administration. The study period was January-June 2007. Antibiotic use in acute
      cystitis was evaluated by means of the defined daily dose (DDD) methodology.
      Quality indicators of antibiotic prescribing proposed by the European
      Surveillance of Antimicrobial Consumption (ESAC) team were the usage rate of
      recommended antibacterials and the usage rate of quinolones. Adherence to the
      available national guidelines was determined. RESULTS: For acute cystitis, 1.06
      DDD per 1000 inhabitant-days antibiotic use was recorded. The ESAC recommended
      antibiotic use in cystitis (23.3%) was well below the recommended range (80
      100%). The consumption of fluoroquinolones was 56.2%, which exceeded the
      recommended range (0-5%) more than 10 times. The adherence rate to the Hungarian
      guidelines ranged between 59.3% and 74.2%. CONCLUSIONS: As both investigated
      disease-specific quality indicators were well outside the acceptable ranges, some
      inappropriateness of antibiotic use in cystitis seems to be present. Adherence
      rates to the different national guidelines were also moderate, but due to the
      general recommendation of quinolones, values should be interpreted with caution.
      New transparent guidelines - issued by the Hungarian Society of Family Physicians
      - should be introduced in Hungary, recommending quinolones only for second-line
      therapy.

PMID- 23547568
TI  - Pneumocystis jirovecii pneumonia in HIV-1-infected patients in the late-HAART era
      in developed countries.
AB  - BACKGROUND: In developed countries with free access to health care, primary
      chemoprophylaxis with co-trimoxazole, and antiretroviral treatment, Pneumocystis
      pneumonia (PCP) in HIV-infected subjects should be restricted to undiagnosed late
      presenters. METHODS: We retrospectively identified confirmed PCP hospital
      admissions in HIV-1 patients (period 1986-2010) and examined their
      characteristics and factors associated with mortality. RESULTS: Three hundred and
      twelve episodes (median CD4 27 cells/MUl) were identified during 3 periods: pre
      HAART (1986-1995), 49%; early-HAART (1996-1999), 17.3%; and late-HAART (2000
      2010), 33.7%. PCP was the initial AIDS-defining diagnosis in only 86 (27.6%).
      Thirty-four (10.9%) patients died during their hospital stay, without a
      significant reduction in mortality in recent periods (p = 0.311). However, the 12
      month mortality decreased through the periods (33.3% to 16.2%; p = 0.003). Drug
      users (p = 0.001) and those naive to HAART (p < 0.001) decreased in the late
      HAART era, while heterosexuals (p = 0.001), immigrants (p < 0.001), and HAART
      initiation before hospital discharge (p < 0.001) increased. A partial pressure of
      oxygen (PaO2) <= 55 (p = 0.04), intensive care admission (p < 0.001), and the
      absence of HAART initiation before discharge (p = 0.02) were correlated with
      mortality. CONCLUSIONS: The epidemiology and 12-month mortality of HIV-1-infected
      subjects with PCP have changed significantly in the late-HAART era, while
      mortality during hospital stay has remained unchanged. HIV diagnosed individuals
      lost to follow-up in care have emerged as the main driver of PCP in developed
      countries. Like HIV late presenters, they are more likely to have AIDS-defining
      illnesses, to be hospitalized, and to die. This finding has important
      implications for the design of better strategies to retain HIV-1-infected
      individuals in care.

PMID- 23547570
TI  - A green and efficient protocol for the synthesis of quinoxaline, benzoxazole and
      benzimidazole derivatives using heteropolyanion-based ionic liquids: as a
      recyclable solid catalyst.
AB  - In this paper, we introduce two nonconventional ionic liquid compounds which are
      composed of propane sulfonate functionalized organic cations and heteropolyanions
      as green solid acid catalysts for the highly efficient and green synthesis of 2,3
      disubstitutedquinoxaline derivatives. These ionic liquids are in the solid state
      at room temperature and the synthesis is carried out via the one-pot condensation
      reaction of various o-phenylenediamine with 1,2-diketone derivatives. Benzoxazole
      and benzimidazole derivatives were also synthesized by these novel catalysts via
      the one-pot condensation from reaction orthoester with o-aminophenol (synthesis
      of benzoxazole derivatives) and ophenylenediamine (synthesis of benzimidazole
      derivatives). All experiments successfully resulted in the desired products. The
      described novel synthesis method has several advantages of safety, mild
      condition, high yields, short reaction times, simplicity and easy workup compared
      to the traditional method of synthesis. 

PMID- 23547572
TI  - Using mindfulness techniques to improve difficult clinical encounters.

PMID- 23547573
TI  - Does screening mammography lead to overdiagnosis of invasive breast cancer?

PMID- 23547574
TI  - Preoperative testing before noncardiac surgery: guidelines and recommendations.
AB  - Preoperative testing (e.g., chest radiography, electrocardiography, laboratory
      testing, urinalysis) is often performed before surgical procedures. These
      investigations can be helpful to stratify risk, direct anesthetic choices, and
      guide postoperative management, but often are obtained because of protocol rather
      than medical necessity. The decision to order preoperative tests should be guided
      by the patient's clinical history, comorbidities, and physical examination
      findings. Patients with signs or symptoms of active cardiovascular disease should
      be evaluated with appropriate testing, regardless of their preoperative status.
      Electrocardiography is recommended for patients undergoing high-risk surgery and
      those undergoing intermediate-risk surgery who have additional risk factors.
      Patients undergoing low-risk surgery do not require electrocardiography. Chest
      radiography is reasonable for patients at risk of postoperative pulmonary
      complications if the results would change perioperative management. Preoperative
      urinalysis is recommended for patients undergoing invasive urologic procedures
      and those undergoing implantation of foreign material. Electrolyte and creatinine
      testing should be performed in patients with underlying chronic disease and those
      taking medications that predispose them to electrolyte abnormalities or renal
      failure. Random glucose testing should be performed in patients at high risk of
      undiagnosed diabetes mellitus. In patients with diagnosed diabetes, A1C testing
      is recommended only if the result would change perioperative management. A
      complete blood count is indicated for patients with diseases that increase the
      risk of anemia or patients in whom significant perioperative blood loss is
      anticipated. Coagulation studies are reserved for patients with a history of
      bleeding or medical conditions that predispose them to bleeding, and for those
      taking anticoagulants. Patients in their usual state of health who are undergoing
      cataract surgery do not require preoperative testing.

PMID- 23547575
TI  - Managing difficult encounters: understanding physician, patient, and situational
      factors.
AB  - Family physicians commonly find themselves in difficult clinical encounters.
      These encounters often leave the physician feeling frustrated. The patient may
      also be dissatisfied with these encounters because of unmet needs, unfulfilled
      expectations, and unresolved medical issues. Difficult encounters may be
      attributable to factors associated with the physician, patient, situation, or a
      combination. Common physician factors include negative bias toward specific
      health conditions, poor communication skills, and situational stressors. Patient
      factors may include personality disorders, multiple and poorly defined symptoms,
      nonadherence to medical advice, and self-destructive behaviors. Situational
      factors include time pressures during visits, patient and staff conflicts, or
      complex social issues. To better manage difficult clinical encounters, the
      physician needs to identify all contributing factors, starting with his or her
      personal frame of reference for the situation. During the encounter, the
      physician should use empathetic listening skills and a nonjudgmental, caring
      attitude; evaluate the challenging patient for underlying psychological and
      medical disorders and previous or current physical or mental abuse; set
      boundaries; and use patient-centered communication to reach a mutually agreed
      upon plan. The timing and duration of visits, as well as expected conduct, may
      need to be specifically negotiated. Understanding and managing the factors
      contributing to a difficult encounter will lead to a more effective and
      satisfactory experience for the physician and the patient.

PMID- 23547576
TI  - Evaluation of occult gastrointestinal bleeding.
AB  - Occult gastrointestinal bleeding is defined as gastrointestinal bleeding that is
      not visible to the patient or physician, resulting in either a positive fecal
      occult blood test, or iron deficiency anemia with or without a positive fecal
      occult blood test. A stepwise evaluation will identify the cause of bleeding in
      the majority of patients. Esophagogastroduodenoscopy (EGD) and colonoscopy will
      find the bleeding source in 48 to 71 percent of patients. In patients with
      recurrent bleeding, repeat EGD and colonoscopy may find missed lesions in 35
      percent of those who had negative initial findings. If a cause is not found after
      EGD and colonoscopy have been performed, capsule endoscopy has a diagnostic yield
      of 61 to 74 percent. Deep enteroscopy reaches into the mid and distal small bowel
      to further investigate and treat lesions found during capsule endoscopy or
      computed tomographic enterography. Evaluation of a patient who has a positive
      fecal occult blood test without iron deficiency anemia should begin with
      colonoscopy; asymptomatic patients whose colonoscopic findings are negative do
      not require further study unless anemia develops. All men and postmenopausal
      women with iron deficiency anemia, and premenopausal women who have iron
      deficiency anemia that cannot be explained by heavy menses, should be evaluated
      for occult gastrointestinal bleeding. Physicians should not attribute a positive
      fecal occult blood test to low-dose aspirin or anticoagulant medications without
      further evaluation.

PMID- 23547577
TI  - Menopausal hormone therapy for the primary prevention of chronic conditions.

PMID- 23547578
TI  - Enlarging mass on the back.

PMID- 23547582
TI  - FPIN's clinical inquiries. Screening for hepatocellular carcinoma in patients
      with hepatitis C virus infection.

PMID- 23547586
TI  - Exercise during pregnancy: a marathon runner's story.

PMID- 23547584
TI  - Biological active analogues of the opioid peptide biphalin: mixed alpha/beta(3)
      peptides.
AB  - Natural residues of the dimeric opioid peptide Biphalin were replaced by the
      corresponding homo-beta(3) amino acids. The derivative 1 containing hbeta(3) Phe
      in place of Phe showed good MU- and delta-receptor affinities (Ki(delta) = 0.72
      nM; Ki(MU) = 1.1 nM) and antinociceptive activity in vivo together with an
      increased enzymatic stability in human plasma.

PMID- 23547587
TI  - New recommendations on motor vehicle safety for child passengers.

PMID- 23547588
TI  - Appropriate use of polypharmacy for older patients.

PMID- 23547589
TI  - Effect of cocoa on blood pressure.

PMID- 23547590
TI  - Management of chronic tendon injuries.
AB  - Chronic tendon injuries present unique management challenges. The assumption that
      these injuries result from ongoing inflammation has caused physicians to rely on
      treatments demonstrated to be ineffective in the long term. Nonsteroidal anti
      inflammatory drugs should be limited in the treatment of these injuries.
      Corticosteroid injections should be considered for temporizing pain relief only
      for rotator cuff tendinopathy. For chronic Achilles tendinopathy (symptoms
      lasting longer than six weeks), an intense eccentric strengthening program of the
      gastrocnemius/ soleus complex improved pain and function between 60 and 90
      percent in randomized trials. Evidence also supports eccentric exercise as a
      first-line option for chronic patellar tendon injuries. Other modalities such as
      prolotherapy, topical nitroglycerin, iontophoresis, phonophoresis, therapeutic
      ultrasound, extracorporeal shock wave therapy, and low-level laser therapy have
      less evidence of effectiveness but are reasonable second-line alternatives to
      surgery for patients who have persistent pain despite appropriate rehabilitative
      exercise.

PMID- 23547591
TI  - Appropriate and safe use of diagnostic imaging.
AB  - Risks of diagnostic imaging include cancer from radiation exposure and
      nephrogenic systemic fibrosis. The increase in volume of imaging between 1980 and
      2006 has led to a sixfold increase in annual per capita radiation exposure. It is
      predicted that 2 percent of future cancers will be caused by radiation from
      computed tomography (CT) exposure. Gadolinium contrast media should be avoided in
      patients with stage 4 or 5 chronic kidney disease because of the risk of
      nephrogenic systemic fibrosis. Appropriate use of imaging based on guidelines for
      specific clinical conditions can reduce these risks. Although noncontrast CT of
      the head is needed to rule out bleeding in patients with suspected stroke within
      the first three hours of symptom onset, diffusion-weighted imaging with magnetic
      resonance of the head and neck is superior to CT within three to 24 hours of
      symptom onset. Headache merits neuroimaging in special circumstances only.
      Sestamibi radioisotope has less radiation than thallium for myocardial perfusion
      imaging. Use of intravenous contrast media with abdominopelvic CT significantly
      increases the diagnostic accuracy for appendicitis. Cholescintigraphy has better
      discrimination to diagnose acute cholecystitis than CT in patients with equivocal
      ultrasonography results. Limited three-view intravenous urography is recommended
      in pregnancy to evaluate urolithiasis if initial ultrasonography findings are
      negative or equivocal. Given that many asymptomatic adults have abnormal findings
      on lumbar spine magnetic resonance imaging, this modality generally should not be
      performed for nonspecific chronic low back pain in the absence of red flags.
      Whole body scanning is not supported by current evidence.

PMID- 23547592
TI  - Prevention of unintentional childhood injury.
AB  - Unintentional injury accounts for 40 percent of childhood deaths annually, most
      commonly from motor vehicle crashes. The proper use of child restraints is the
      most effective strategy to prevent injury or death. Motor vehicle restraint
      guidelines have recently been revised to an age-based system that delays the
      progression in type of restraint for most children. Strategies to prevent
      suffocation in children include using appropriate bedding, positioning babies on
      their backs to sleep, and removing items from the sleep and play environment that
      could potentially entrap or entangle the child. Fencing that isolates a swimming
      pool from the yard and surrounding area and "touch" adult supervision (i.e., an
      adult is in the water and able to reach and grab a child) have been shown to be
      most effective in preventing drownings. Swimming lessons are recommended for
      children older than four years. Poison prevention programs have been shown to
      improve prevention behavior among caregivers, but may not decrease poisoning
      incidence. Syrup of ipecac is not recommended. Smoke detector maintenance, a home
      escape plan, and educating children about how to respond during a fire emergency
      are effective strategies for preventing fire injuries or death. Fall injuries may
      be reduced by not using walkers for infants and toddlers or bunk beds for
      children six years and younger. Consistent helmet use while bicycling reduces
      head and brain injuries. Although direct counseling by physicians appears to
      improve some parental safety behaviors, its effect on reducing childhood injuries
      is uncertain. Community-based interventions can be effective in high-risk
      populations.

PMID- 23547596
TI  - Generalized annular skin lesions.

PMID- 23547599
TI  - Trends in physician supply and population growth.
AB  - The physician workforce has steadily grown faster than the U.S. population over
      the past 30 years, context that is often absent in conversations anticipating
      physician scarcity. Policy makers addressing future physician shortages should
      also direct resources to ensure specialty and geographic distribution that best
      serves population health .

PMID- 23547600
TI  - Article on CFS does not reflect current best treatment practices.

PMID- 23547601
TI  - Preventing injuries: how can I keep my child safe?

PMID- 23547602
TI  - The comparison between the calculated and HPLC-predicted lipophilicity parameters
      for selected groups of drugs.
AB  - The parameters of lipophilicity for three different groups of drugs (twelve
      analgesics drugs, eleven cardiovascular system drugs, and thirty six compounds
      characterized by divergent pharmacological activity) were experimentally
      determined by HPLC methods as well as calculated using various computer programs
      (HyperChem, ACD/Labs, ChemAxon, Dragon and VCCLab). The relationships between
      experimental (chromatographic) parameters of lipophilicity (log k and log kw) and
      the chemical structure of the studied compounds, and their comparison due to
      their lipophilic and hydrophilic character were presented. Moreover, the
      experimental and calculated values of parameters of lipophilicity were correlated
      and compared. Finally, both these groups of parameters of lipophilicity were
      analyzed using PCA or FA methods for the classification of studied compounds
      according to their chemical structures and pharmacological activity. 

PMID- 23547604
TI  - Physician resilience is an important skill.

PMID- 23547603
TI  - Think again.

PMID- 23547605
TI  - Physician resilience is an important skill.

PMID- 23547606
TI  - Physician resilience is an important skill.

PMID- 23547607
TI  - Author's response: physician resilience is an important skill.

PMID- 23547608
TI  - Envisioning new roles for medical assistants: strategies from patient-centered
      medical homes.

PMID- 23547609
TI  - A practical guide to emergency preparedness for office-based family physicians.

PMID- 23547610
TI  - Redesigning your work space to support team-based care.

PMID- 23547611
TI  - Medication adherence: we didn't ask and they didn't tell.

PMID- 23547620
TI  - The relational soul of family medicine.

PMID- 23547621
TI  - Traumatic brain injury: oxidative stress and neuroprotection.
AB  - SIGNIFICANCE: A vast amount of circumstantial evidence implicates high energy
      oxidants and oxidative stress as mediators of secondary damage associated with
      traumatic brain injury. The excessive production of reactive oxygen species due
      to excitotoxicity and exhaustion of the endogenous antioxidant system induces
      peroxidation of cellular and vascular structures, protein oxidation, cleavage of
      DNA, and inhibition of the mitochondrial electron transport chain. RECENT
      ADVANCES: Different integrated responses exist in the brain to detect oxidative
      stress, which is controlled by several genes termed vitagens. Vitagens encode for
      cytoprotective heat shock proteins, and thioredoxin and sirtuins. CRITICAL ISSUES
      AND FUTURE DIRECTIONS: This article discusses selected aspects of secondary brain
      injury after trauma and outlines key mechanisms associated with toxicity,
      oxidative stress, inflammation, and necrosis. Finally, this review discusses the
      role of different oxidants and presents potential clinically relevant molecular
      targets that could be harnessed to treat secondary injury associated with brain
      trauma.

PMID- 23547622
TI  - Hippocrates of Cos.

PMID- 23547623
TI  - Oral carbohydrate supplementation reduces preoperative discomfort in laparoscopic
      cholecystectomy.
AB  - The aim of this study was to investigate the effects of oral carbohydrate
      solution (CHO) on perioperative discomfort, biochemistry, hemodynamics, and
      patient satisfaction in elective surgery patients under general anesthesia. Sixty
      cases in ASA I-II group who were planned to have operation under general
      anesthesia were included in the study. The cases were randomly divided into two
      groups having 30 subjects in each. The patients in the study group were given CHO
      in the evening prior to the surgery and 2-3 hr before the anesthesia while
      routine fasting was applied in the control group. In the study group; 2-3 hr
      before the surgery; malaise, thirst, hunger, and weakness; just before the
      surgery malaise, thirst, hunger, and fatigue; 2 hr after the operation thirst,
      hunger, weakness, and concentration difficulty; 24 hr after the operation malaise
      and weakness were found significantly lower. Fasting blood glucose (FBG) level
      was found to be higher in the control group at the 90th min of the operation.
      Gastric volumes were higher in the control group; gastric pH values were found
      significantly higher in the study group. The level of anxiety and depression risk
      rate were found lower in the study group. In conclusion, preoperative CHO reduces
      perioperative discomfort and improves perioperative well being when compared to
      overnight fasting.

PMID- 23547624
TI  - Laparoscopic cholecystectomy with previous gastrectomy.
AB  - INTRODUCTION: To evaluate the safety and efficacy of laparoscopic cholecystectomy
      (LC) in patients with a history of gastrectomy. METHODS: The clinical data of
      9,403 consecutive patients who underwent LC from January 2003 to September 2010
      in our hospital were retrospectively analyzed; 30 of them had undergone previous
      gastrectomy. We compared the operative duration, hospitalization, and conversion
      rate between patients with, and those randomized selected patients without, a
      history of gastrectomy. RESULTS: All patients were treated by laparoscopic
      procedure successfully. The mean operative duration (55.00 min vs. 29.63 min, P <
      .05) and mean hospitalization duration (4.57 days vs. 3.00 days, P < .05) were
      significantly longer in the patients with a history of gastrecotomy. There are no
      complications such as bile duct and bowel injury in control group, however two
      bile duct injuries emerged in the observed group, which required surgical
      intervention. CONCLUSIONS: Although the operation is difficult, LC is a safe and
      effective treatment for the patients with a history of gastrectomy.

PMID- 23547626
TI  - Commentary on "COPD causation and workplace exposures: an assessment of agreement
      among expert clinical raters".

PMID- 23547627
TI  - Fatigue in COPD and the impact of respiratory symptoms and heart disease--a
      population-based study.
AB  - BACKGROUND: Fatigue is reported in COPD and in heart disease; however, there are
      hardly any population based data on the relationship between these conditions.
      AIM: To describe fatigue in relation to COPD by disease severity and to evaluate
      the impact of respiratory symptoms and heart disease. METHODS: Data were
      collected in 2007 from the OLIN COPD study; 564 subjects with COPD (FEV1/FVC <
      0.70) and a distribution of disease severity representative for the general
      population, and 786 subjects without COPD. The Functional Assessment of Chronic
      Illness Therapy (FACIT)-Fatigue scale was used to assess fatigue (0-52); lower
      scores represent worse fatigue. RESULTS: Median FACIT-F score was 44.0 in COPD
      defined by merely spirometric criteria and 42.0 in COPD also reporting
      respiratory symptoms, significantly lower compared to 46.0 in non-COPD (p = 0.006
      and p < 0.001), and decreased by disease severity. The score was lower in COPD
      stage >= II and in COPD with respiratory symptoms already from stage I when
      compared to non-COPD. Subjects with heart disease reported lower scores than
      those without heart disease in COPD by all stages and in non-COPD. COPD with
      respiratory symptoms stage >=II remained a significant risk factor for clinically
      significant fatigue also when adjusted for gender, age, heart disease and smoking
      habits (stage II OR 1.65, CI 1.17-2.31 and stage III-IV OR 2.66, CI 1.11-6.36).
      CONCLUSION: Fatigue is common in COPD, and is affected by respiratory symptoms
      and concomitant heart disease. In COPD with respiratory symptoms stage >= II,
      there is an increased risk for clinically significant fatigue.

PMID- 23547628
TI  - COPD causation and workplace exposures: an assessment of agreement among expert
      clinical raters.
AB  - BACKGROUND: Although occupational exposure is a known risk factor for Chronic
      Obstructive Pulmonary Disease (COPD), it is difficult to identify specific
      occupational contributors to COPD at the individual level to guide COPD
      prevention or for compensation. The aim of this study was to gain an
      understanding of how different expert clinicians attribute likely causation in
      COPD. METHODS: Ten COPD experts and nine occupational lung disease experts
      assigned occupational contribution ratings to fifteen hypothetical cases of COPD
      with varying combinations of occupational and smoking exposures. Participants
      rated the cause of COPD as the percentage contribution to the overall attribution
      of disease for smoking, occupational exposures and other causes. RESULTS:
      Increasing pack-years of tobacco smoking was associated with significantly
      decreased proportional occupational causation ratings. Increasing weighted
      occupational exposure was associated with increased occupational causation
      ratings by 0.28% per unit change. Expert background also contributed
      significantly to the proportion of occupational causation rated, with COPD
      experts rating on average a 9.4% greater proportion of occupational causation per
      case. CONCLUSION: Our findings support the notion that respiratory physicians are
      able to assign attribution to different sources of causation in COPD, taking into
      account both smoking and occupational histories. The recommendations on whether
      to continue to work in the same job also differ, the COPD experts being more
      likely to recommend change of work rather than change of work practice.

PMID- 23547629
TI  - Impaired carbon monoxide diffusing capacity is the strongest predictor of
      exercise intolerance in COPD.
AB  - BACKGROUND: Exercise intolerance is a hallmark of chronic obstructive pulmonary
      disease (COPD) and forced expiratory volume in one second (FEV1) is the
      traditional metric used to define the severity of COPD. However, there is
      dissociation between FEV1 and exercise capacity in a large proportion of subjects
      with COPD. The aim of this study was to investigate whether other lung function
      parameters have an additive, predictive value for exercise capacity and whether
      this differs according to the COPD stage. METHODS: Spirometry, body
      plethysmography and diffusing capacity for carbon monoxide (DLCO) were performed
      on 88 patients with COPD GOLD stages II-IV. Exercise capacity (EC) was determined
      in all subjects by symptom-limited, incremental cycle ergometer testing. RESULTS:
      Significant relationships were found between EC and the majority of lung function
      parameters. DLCO, FEV1 and inspiratory capacity (IC) were found to be the best
      predictors of EC in a stepwise regression analysis explaining 72% of EC. These
      lung function parameters explained 76% of EC in GOLD II, 72% in GOLD III and 40%
      in GOLD IV. DLCO alone was the best predictor of exercise capacity in all GOLD
      stages. CONCLUSIONS: Diffusing capacity was the strongest predictor of exercise
      capacity in all subjects. In addition to FEV1, DLCO and IC provided a
      significantly higher predictive value regarding exercise capacity in COPD
      patients. This suggests that it is beneficial to add measurements of diffusing
      capacity and inspiratory capacity when clinically monitoring COPD patients.

PMID- 23547630
TI  - Microalbuminuria in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Microalbuminuria is an important risk factor for cardiovascular
      diseases. Microalbuminuria may be seen due to hypoxemia in patients with chronic
      obstructive pulmonary disease (COPD). OBJECTIVES: In this study, we investigated
      prevalence and relationship of microalbuminuria with clinical and physiological
      parameters in patients with COPD. METHOD: During the research, 66 consecutive
      patients with COPD and 40 cases smokers with normal spirometry were included. The
      urinary albumin creatinin ratio (UACR) was calculated according to previously
      described formula. The presence of microalbuminuria was defined as UACR being
      >=20 in men and >=30 in women. The severity index of chronic diseases was
      evaluated by using MCIRS. RESULTS: The rate of presence of microalbuminuria and
      UACR were higher in patients with COPD than smokers with normal spirometry.
      Pearson correlation analysis showed a significant inverse relationship between
      UACR and PaO2, FEV1%, FVC%. On the other hand, there was a positive relationship
      between UACR and BODE index. There was a significant relationship between the
      presence of microalbuminuria with PaO2 and BODE index. In the linear regression
      model, there was a negative relationship between UARC and PaO2 yet there was a
      significantly positive relationship between UARC and MCIRS score, BODE index. In
      the logistic regression model, the presence of microalbuminuria showed
      significant associations with PaO2, BODE index. CONCLUSION: Microalbuminuria may
      be seen in patients with COPD, depending on the severity of disease and
      hypoxemia. Microalbuminuria in patients with severe COPD should be examined in
      regular periods for risk of cardiovascular morbidity or mortality.

PMID- 23547631
TI  - The effect of continuous positive airway pressure on stair-climbing performance
      in severe COPD patients.
AB  - Stair climbing is associated with dynamic pulmonary hyperinflation and the
      development of severe dyspnea in patients with chronic obstructive pulmonary
      disease (COPD). This study aimed to assess whether (i) continuous positive airway
      pressure (CPAP) applied during stair climbing prevents dynamic hyperinflation and
      thereby reduces exercise-induced dyspnea in oxygen-dependent COPD-patients, and
      (ii) the CPAP-device and oxygen tank can be carried in a hip belt. In a
      randomised cross-over design, oxygen-dependent COPD patients performed two stair
      climbing tests (44 steps): with supplemental oxygen only, then with the addition
      of CPAP (7 mbar). The oxygen tank and CPAP-device were carried in a hip belt
      during both trials. Eighteen COPD patients were included in the study. Although
      all patients could tolerate stair climbing with oxygen alone, 4 patients were
      unable to perform stair climbing while using CPAP. Fourteen COPD patients (mean
      FEV1 36 +/- 14% pred.) completed the trial and were analyzed. The mean flow rate
      of supplemental oxygen was 3 +/- 2 l/min during stair climbing. Lung
      hyperinflation, deoxygenation, hypoventilation, blood lactate production, dyspnea
      and the time needed to manage stair climbing were not improved by the application
      of CPAP (all p > 0.05). However, in comparison to climbing with oxygen alone,
      limb discomfort was reduced when oxygen was supplemented with CPAP (p = 0.008).
      In conclusion, very severe COPD patients are able to carry supporting devices
      such as oxygen tanks or CPAP-devices in a hip belt during stair climbing.
      However, the application of CPAP in addition to supplemental oxygen during stair
      climbing prevents neither exercise-induced dynamic hyperinflation, nor dyspnea.

PMID- 23547632
TI  - Early detection of COPD in primary care: the Copenhagen COPD screening project.
AB  - OBJECTIVE: To evaluate the effectiveness of a screening programme for COPD in
      primary care. MATERIAL/METHODS: Subjects aged 65 years or older registered with a
      general practitioner in Copenhagen were asked to complete a questionnaire on
      smoking status and symptoms of COPD. If they were smokers or former smokers or if
      morning cough with sputum and/or dyspnoea was present, subjects were defined as
      "at risk of COPD" and were invited to undergo spirometric examination. RESULTS:
      Of the 7103 subjects who met the study criteria, 81.2% responded to the
      questionnaire. Of these, 58.5% were at risk of COPD. Of those at risk, 40%
      underwent a spirometric examination. COPD was classified as mild in 252 (42.3%),
      moderate in 258 (43.3%) and severe-very severe in 86 subjects (14.4%). The
      participation rate was significantly higher among subjects invited for spirometry
      at a healthcare centre compared to general practice. CONCLUSIONS: Our findings
      suggest that a questionnaire can be used as a screening tool to identify subjects
      at risk of COPD. Furthermore, the study shows that more than half the subjects
      aged 65 years and above were at risk of COPD and required clinical assessment.
      Willingness to undergo spirometric examination depends on the location of the
      screening.

PMID- 23547633
TI  - Abnormal renal resistive index in patients with mild-to-moderate chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Arterial rigidity and endothelial dysfunction are systemic
      manifestations of chronic obstructive pulmonary disease (COPD). The decrease in
      renal vascular resistance in order to adapt the increase in glomerular filtration
      rate after oral protein loading is known as normal renal functional reserve. We
      tested the hypothesis that COPD patients, even in those with mild-to-moderate
      airflow obstruction, are affected by systemic inflammation associated with
      abnormal renal functional reserve. MATERIALS AND METHODS: The study enrolled 24
      current smokers with a cigarette smoking history >= 25 pack-years and 8
      nonsmokers with normal spirometry as control. Doppler sonography detected the
      renal resistive index (RRI) before and after oral protein loading to determine
      the renal functional reserve. Pulmonary function and serum tumor necrosis factor
      alpha (TNF-alpha) levels were analyzed to compare with the renal functional
      reserve. RESULTS: The smokers were stratified into 3 groups (Group 1: smokers
      with normal spirometry, Group 2: mild COPD, Group 3: moderate COPD); nonsmokers
      as Group 4. The baseline RRI levels were similar in Group 1 and Group 4. After
      protein loading, the RRI elevated in all smoking groups; moreover, Group 3 had
      the highest RRI and with longer duration than other groups. The smokers with
      higher serum TNF-alpha levels had a longer RRI elevation. Multiple linear
      regression revealed forced expiratory volume in one second (FEV1), serum TNF
      alpha levels and aging were independently predictive factors of impaired renal
      functional reserve. CONCLUSIONS: A greater impairment in renal functional reserve
      of COPD patients was correlated with more severe airway obstruction and
      inflammation.

PMID- 23547634
TI  - Differences in adjustment between individuals with alpha-1 antitrypsin deficiency
      (AATD)-associated COPD and non-AATD COPD.
AB  - Smokers who have severe alpha-1 antitrypsin deficiency (AATD) are at risk for
      developing COPD earlier in life than smokers without AATD, and are likely to
      experience challenges adjusting to their illness because they are in a highly
      productive life stage when they are diagnosed with COPD. This study examined
      whether individuals with AATD-associated COPD differ from individuals with non
      AATD COPD with regard to depression, anxiety, dyspnea, and health-related quality
      of life (HRQL). Cross-sectional data were collected via self-report
      questionnaires completed by 480 individuals with non-AATD COPD and 578
      individuals with AATD-associated COPD under protocols with IRB approval. Multiple
      linear regression models were used to test whether individuals with non-AATD COPD
      differed from individuals with AATD-associated COPD with regard to depression,
      anxiety, dyspnea, and HRQL. All models adjusted for demographic and health
      characteristics. Individuals with AATD-associated COPD did not report more
      symptoms of depression or anxiety; however, they did report more dyspnea (B =
      0.31, 95% CI = 0.16 to 0.47, p < 0.001) and impairment in HRQL (B = 4.75, 95% CI
      = 2.10 to 7.41, p < 0.001) than other individuals with COPD. Individuals with
      AATD-associated COPD were more likely to be a member of a couple (rather than
      single) and had a higher level of education when compared to individuals with non
      AATD COPD. Resources available to persons with AATD-associated COPD, such as
      being in a serious relationship and having higher education, may offset the
      effect of age when considering symptoms of depression and anxiety in patients
      with COPD.

PMID- 23547635
TI  - Distal leg muscle function in patients with COPD.
AB  - Quadriceps muscle weakness and increased fatigability are well described in
      patients with chronic obstructive pulmonary disease (COPD). Whether these
      functional alterations also exist in distal leg muscles in patients with COPD is
      uncertain. Fifteen patients with COPD and 15 aged-matched healthy controls
      performed a 12-minute standardized treadmill exercise during which a fixed total
      expense of 40 Kcal was reached. The strength of i) dorsiflexors, ii) plantar
      flexors and iii) quadriceps was assessed at rest and after exercise using maximal
      voluntary contraction (MVC) and potentiated twitch force (Twpot). Resting MVC and
      Twpot were significantly lower in patients with COPD when compared with controls
      respectively for i) dorsiflexors (24.9 +/- 8.4 vs. 31.2 +/- 8.5 Nm, p < 0.05 and
      4.3 +/- 1.3 vs. 5.7 +/- 1.8 Nm, p < 0.05), ii) plantar flexors (49.5 +/- 11.8 vs.
      62.1 +/- 19.6 Nm, p < 0.05 and 10.8 +/- 3.5 vs. 13.4 +/- 2.7 Nm, p < 0.05), and
      iii) quadriceps muscles. There was a greater force loss in the distal leg muscles
      15 minutes post-exercise in patients with COPD, while the strength of the
      quadriceps muscle remained stable in both groups. Patients with COPD had weaker
      dorsiflexor and plantar flexor muscles when compared to age-matched healthy
      controls. In addition, when exposed to the same absolute walking task, the
      fatigability of the distal leg muscles was higher in patients with COPD.

PMID- 23547637
TI  - COPD assessment test --rationale, development, validation and performance.

PMID- 23547639
TI  - Melancholia: a distinct entity?

PMID- 23547640
TI  - A case for reprising and redefining melancholia.
AB  - OBJECTIVE: To identify limitations to severity-based classifications of
      depression, and to argue for positioning melancholia as a distinct melancholic
      subtype. METHOD: An overview of relevant literature was conducted. RESULTS:
      First, dimensionalizing depressive disorders effectively aggregates multiple
      heterogeneous depressive types and syndromes, and thus limits, if not prevents,
      identification of differential causes and treatments. Second, the melancholic
      depressive subtype can be defined with some relative precision, and that as it
      shows quite distinct differential treatment responsiveness, identification should
      be a clinical priority. CONCLUSION: Melancholia can be positioned and classified
      as a distinct depressive subtype.

PMID- 23547641
TI  - Melancholia: past and present.
AB  - OBJECTIVE: To investigate commonalities in the clinical presentation of
      melancholia over time. METHOD: I conducted a comparative study to 2
      epidemiologically complete databases from 1875-1924 and 1995-2005. RESULTS:
      Patients in the historical period (1875-1924, compared with 1995-2005) with a
      diagnosis of melancholia show a classic profile of endogenous onset, with
      remission after 6 months, neurovegetative features, and, commonly, psychosis. The
      incidence of psychotic presentations appears to have fallen in recent decades.
      Patients in the contemporary period (1995-2010, compared with 1875-1924) at first
      admission for severe depressive disorders are more likely at an older age, more
      likely to go on to die by suicide, and will have much more frequent admissions.
      CONCLUSIONS: The data from this study support classical perceptions of
      melancholia. The poor outcomes in contemporary cases of severe depressive
      disorders support arguments for distinguishing between melancholia and other
      depressive disorders.

PMID- 23547642
TI  - The impact of memantine and cholinesterase inhibitor initiation for Alzheimer
      disease on the use of antipsychotic agents: analysis using the Regie de
      l'Assurance Maladie du Quebec database.
AB  - OBJECTIVE: Patients with Alzheimer disease (AD) show a high incidence of
      behavioural and psychological symptoms of dementia, which often lead to the
      prescription of antipsychotics. Our study sought to assess the impact of the
      initiation of memantine or cholinesterase inhibitors (ChEIs) on the use of
      antipsychotics. METHOD: A retrospective cohort study was conducted using data
      from the Quebec provincial health plan database. Patients included in our study
      had received a diagnosis of AD and were initial users of memantine or ChEIs. The
      proportion of patients who used antipsychotics was estimated using prescription
      data dating back to 1 year before and to 1 year after the first prescription of
      memantine or ChEIs. The difference between the slopes corresponding to the
      periods pre- and postmemantine or ChEIs was analyzed using an interrupted time
      series design. RESULTS: The percentage of antipsychotic users increased by 118.3%
      before and by 68.3% after initiation of a ChEI, and increased by 68.6% before and
      by 7.0% after initiation of memantine. Antipsychotic trends pre- and post-ChEI
      initiation were not statistically different (P = 0.89), while a statistical
      difference was observed when comparing the antipsychotic trends pre- and
      postmemantine initiation (P < 0.001). CONCLUSIONS: The initiation of memantine,
      unlike ChEIs, has a notable stabilization effect on the prescription of
      antipsychotics in patients with AD.

PMID- 23547643
TI  - The costs associated with antidepressant use in depression and anxiety in
      community-living older adults.
AB  - OBJECTIVE: To determine the costs associated with antidepressant (AD) use by
      depression and anxiety status in a public-managed health care system. METHODS:
      Data were obtained from a population-based health survey of 1869 older adults.
      Depression and anxiety were based on the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, criteria and measured at 2 time points 1 year
      apart. AD and health service use and costs were identified from provincial
      administrative databases and included hospitalizations, physician fees,
      outpatient medications, and ambulatory visits. Patient costs considered were
      related to drug copayments, transportation, and time spent seeking medical care.
      Annual costs associated with AD use were studied as a function of mental health
      status at baseline and follow-up interviews (persistence, incidence, remission,
      or no illness). Generalized linear models with a gamma distribution were used to
      control for individual factors. RESULTS: The costs incurred by participants using
      ADs as a whole (17.8%) reached $6678 (95% CI $5449 to $8182), significantly more
      than in participants not using ADs ($4698; 95% CI $3710 to $5949). AD use was
      associated with greater total adjusted costs among respondents with no depression
      (adjusted difference = $1769; 95% CI $236 to $3702) and no anxiety (adjusted
      difference = $1845; 95% CI $203 to $3486). CONCLUSION: The results showed that AD
      use was not associated with cost savings in any group, and indeed with greater
      costs among participants who were neither depressed nor anxious at any time
      point. Future cost studies may consider the analyses of different AD classes
      regarding the different clinical mental health profiles in older adults.

PMID- 23547644
TI  - Age at immigration to Canada and the occurrence of mood, anxiety, and substance
      use disorders.
AB  - OBJECTIVE: The process of migration and resettlement has been associated with
      increased risk for psychiatric illness. Our study sought to examine the
      association between age at immigration and risk for mood, anxiety, and substance
      use disorders (SUDs) among adult immigrants in Canada. METHOD: Data from the
      Canadian Community Health Survey: Mental Health and Well-Being, a cross-sectional
      study of psychiatric disorder conducted in 2002, was used to identify a
      representative sample of adult immigrants in Canada (n = 4946). Logistic
      regression was used to examine the association between age at immigration (0 to 5
      years, 6 to 17 years, and 18 years and older) and 12-month prevalence of mood and
      anxiety disorders, and SUDs. RESULTS: Immigrants who arrived prior to age 6 years
      reported the highest risk for mood (OR 3.41; 95% CI 1.7 to 7.0) and anxiety
      disorders (OR 6.89; 95% CI 3.5 to 13.5), compared with those who immigrated at
      the age of 18 years or older, after adjusting for covariates, including duration
      of residence. CONCLUSIONS: Younger age at immigration was associated with
      increased risk of having a current mood disorder, anxiety disorder, or SUD. These
      findings speak to the importance of developing and evaluating targeted prevention
      programs for young immigrant children and adolescents.

PMID- 23547645
TI  - Comparative safety of antipsychotics: another look at the risk of diabetes.
AB  - OBJECTIVE: The association between the use of antipsychotics and diabetes
      mellitus (DM) is still unclear, as depicted by several conflicting reports. Our
      study aims to assess the risk of DM in new users of antipsychotics. METHODS: Our
      nested case-control study used the Quebec Health Insurance Board databases.
      People in the source cohort were DM-free and had initiated an antipsychotic
      treatment. Subjects were cohort members who initiated an antidiabetic or had a
      diagnosis of DM during their follow-up period. Three variables were used to
      assess antipsychotic exposure: the antipsychotic used (any typical, clozapine,
      olanzapine, quetiapine, risperidone, or more than 1 drug); the number of 30-day
      periods of use; and antipsychotic use at index date (current or past). A paired
      multivariate logistic regression model was used to calculate adjusted odds
      ratios. RESULTS: Among the 88 467 people included in the cohort, 6109 subjects
      with DM were identified and were matched to 61 090 control subjects. New users of
      quetiapine were less likely to develop DM than new users of typical
      antipsychotics (OR, 0.89; 95% CI 0.81 to 0.99). The risk of DM was not
      statistically different across the atypical antipsychotics. A longer exposure to
      any antipsychotic (for each 30-day period, OR 1.009; 95% CI 1.006 to 1.011) and
      current use of antipsychotics (OR 1.26; 95% CI 1.17 to 1.36) were associated with
      DM. CONCLUSION: These results suggest that metabolic parameters of people exposed
      to antipsychotics should be monitored, irrespective of the drug taken, among the
      drugs available at the time of analysis.

PMID- 23547646
TI  - Religious attendance, spirituality, and major depression in Canada: a 14-year
      follow-up study.
AB  - OBJECTIVE: Although there have been numerous studies on the relation of religion
      or spirituality and major depression, few used a longitudinal, nationally
      representative sample. Our study sought to examine the effect of religious
      attendance, self-declared importance of spiritual values, and self-identification
      as a spiritual person on major depression. METHOD: Data coming from 8 waves (1994
      to 2008) of the longitudinal Canadian National Population Health Survey were
      used. People (n = 12 583) who were not depressed at baseline (1994) were followed
      during 14 years. Depression at each cycle was assessed using the Composite
      International Interview-Short Form for Major Depression. Weibull proportional
      hazards regression was used to model longitudinal risk of depression, with
      religious attendance or spirituality as a predictor. RESULTS: At baseline,
      monthly religious attenders tended to be older, female, and married, compared
      with occasional and nonattenders. The Weibull regression model revealed a 22%
      lower risk of depression for monthly attenders (hazard ratio 0.78, 95% CI 0.63 to
      0.95), compared with nonattenders, after controlling for age, household income,
      family and personal history of depression, marital status, education, and
      perceived social support. Neither self-reported importance of spiritual values
      nor identification as a spiritual person was related to major depressive
      episodes. CONCLUSION: Attending religious services at least monthly has a
      protective effect against major depression.

PMID- 23547647
TI  - The impact of the type of insurance plan on adherence and persistence with
      antidepressants: a matched cohort study.
AB  - OBJECTIVE: To compare adherence to, and persistence with, antidepressants (AD) in
      Quebec patients who are covered by private and public drug insurance. METHOD: A
      matched cohort study was conducted using prescription claims databases: reMed, a
      medication data registry for Quebec residents covered by private drug insurance,
      and Regie de l'assurance maladie du Quebec database for Quebec residents with
      public drug insurance. Patients were aged 18 to 64 years and filled at least 1
      prescription for an AD in monotherapy between December 2007 and September 2009
      (194 privately and 2055 publicly insured patients). Adherence over 1 year was
      estimated using the proportion of prescribed days covered (PPDC). The difference
      in mean PPDC between patients with private and public drug insurance was
      estimated with linear regression. Persistence was compared between the groups
      with a Cox regression model. RESULTS: The PPDC was 86.4% (95% CI 83.3% to 89.5%)
      in privately insured and 82.2% (95% CI 78.5% to 85.9%) in publicly insured
      patients and the adjusted mean difference was 5.1% (95% CI 1.6% to 8.6%).
      Persistence was 51.0% in the private group and 19.7% in the public group at 1
      year (P < 0.001); the adjusted hazard ratio was 0.49 (95% CI 0.30 to 0.79).
      CONCLUSION: Better adherence and persistence were observed in privately insured
      patients. Adherence difference may be due to lower copayment among privately
      insured patients.

PMID- 23547648
TI  - [Early onset bipolar disorder: validation from admixture analyses and
      biomarkers].
AB  - OBJECTIVES: Bipolar affective disorder (BD) is a multifactorial disorder with
      heterogeneous clinical presentations, in particular according to age at onset
      (AAO). The relevance of such an indicator has been discussed as a potential
      specifier in future nosographical classification. METHOD: We summarize available
      evidence of admixture analyses and biomarkers in early onset BD. RESULTS:
      Numerous clinical arguments have led us to conclude that the early onset BD
      subgroup is clinically homogeneous, with particular, recurrent, and severe
      characteristics.Eight admixture studies have demonstrated the existence of 3
      subgroups of patients with BD according to AAO (early, intermediate, and late
      AAO), with 2 cut-off points of 21 (21.33) [SD 1.41]) and 35 years (34.67 [SD
      5.52]). Differential clinical features and outcome measures characterize the
      early onset subgroup: higher rate of suicide attempts, rapid cycling, alcohol and
      drugs misuse, psychotic symptoms, and comorbid anxiety disorders. This may
      partially explain the delayed diagnosis and late initiation of mood stabilizers.
      Genetic, biological, imaging, and cognitive arguments may be considered as
      potential markers in providing external validity of the existence of this early
      onset subgroup. Implementation of AAO in the algorithms of treatment may be
      discussed, although the level of proof for focused medication strategies remains
      to be consolidated. CONCLUSION: Given the high frequency (44.80%) of early onset
      BD, awareness of clinicians should be stimulated to provide an early and accurate
      detection, preventive strategies, and possibly specific treatments.The
      forthcoming DSM-5 should include AAO as a specifier, given its relevance for
      course and outcome.

PMID- 23547649
TI  - Nothing gained: an explorative study of the long-term effects of perceived
      maternal feeding practices on women's and men's adult BMI, body image
      dissatisfaction, and disordered eating.
AB  - The objective of the studies presented here was the prediction of adult body mass
      index (BMI), body image dissatisfaction, and disordered eating from recalled
      maternal child feeding practices. Studies 1 and 2 sampled women from the
      community, and found that recalled childhood feeding practices predicted both
      current BMI and current disordered eating. Daughters whose mothers pressured them
      to eat as children had lower BMIs as adults. The more a mother was concerned
      about her daughter's weight as a child, and the more she restricted fatty food
      intake, the less the woman was satisfied with her current body image. Disordered
      eating of adult women was positively related to their mothers' restriction of
      their fatty food intake as children, and negatively related to the mothers'
      monitoring of their food intake as children. Combining the samples and
      subdividing them into four BMI intervals showed that the obese women were higher
      on all but one of the recalled maternal child feeding practices, as well as on
      disordered eating and body dissatisfaction. Age was found to be positively
      related to BMI and drive for thinness, but not to body dissatisfaction or
      disordered eating, with older women having higher BMI and more drive for
      thinness. Study 3 sampled adult men from the community and found that recalled
      maternal child feeding practices predicted adult BMI and disordered eating for
      men, as well as for women. Considerable sex differences were found for all study
      variables. Recollection of maternal child feeding practices may have a formative
      role in the development of body image, disordered eating, and BMI for men and
      women, even into adulthood. 

PMID- 23547650
TI  - Plasmonic imaging of brownian motion of single DNA molecules spontaneously
      binding to Ag nanoparticles.
AB  - We find the spontaneous binding of single DNA molecules to uncoated silver
      nanoparticles (AgNPs) in aqueous solution with Mn(2+) (3 mM). From dark-field
      optical microscopic imaging of AgNPs bound to DNA molecules, we demonstrate
      analysis of the Brownian motion of single DNA molecules via plasmon resonance
      elastic light scattering. Our results provide that the plasmonic imaging
      technique is free from photobleaching and blinking and thus is useful in long
      time observations of single-molecule DNA dynamics.

PMID- 23547651
TI  - Multimetallic complexes and functionalized nanoparticles based on oxygen- and
      nitrogen-donor combinations.
AB  - The versatile precursors [Ru(CH?CHC6H4Me-4)Cl(CO)(BTD)(PPh3)2] (BTD = 2,1,3
      benzothiadiazole) and [Ru(C(C=CPh)?CHPh)Cl(CO)(PPh3)2] were treated with
      isonicotinic acid, 4-cyanobenzoic acid, and 4-(4-pyridyl)benzoic acid under basic
      conditions to yield [Ru(vinyl)(O2CC5H4N)(CO)(PPh3)2], [Ru(vinyl)(O2CC6H4CN
      4)(CO)(PPh3)2], and [Ru(vinyl){O2CC6H4(C5H4N)-4}(CO)(PPh3)2], respectively. The
      osmium analogue [Os(CH?CHC6H4Me-4)(O2CC5H4N)(CO)(PPh3)2] was also prepared. cis
      [RuCl2(dppm)2] was used to prepare the cationic compounds
      [Ru(O2CC5H4N)(dppm)2](+) and [Ru{O2CC6H4(C5H4N)-4}(dppm)2](+). The treatment of 2
      equiv of [Ru(C(C=CPh)?CHPh)(O2CC5H4N)(CO)(PPh3)2] and [Ru(O2CC5H4N)(dppm)2](+)
      with AgOTf led to the trimetallic compounds
      [{Ru(C(C=CPh)?CHPh)(CO)(PPh3)2(O2CC5H4N)}2Ag](+) and
      [{Ru(dppm)2(O2CC5H4N)}2Ag](3+). In a similar manner, the reaction of
      [Ru(O2CC5H4N)(dppm)2](+) with PdCl2 or K2PtCl4 yielded
      [{Ru(dppm)2(O2CC5H4N)}2MCl2](2+) (M = Pd, Pt). The reaction of
      [RuHCl(CO)(BTD)(PPh3)2] with HC=CC6H4F-4 provided [Ru(CH?CHC6H4F
      4)Cl(CO)(BTD)(PPh3)2], which was treated with isonicotinic acid and base to yield
      [Ru(CH?CHC6H4F-4)(O2CC5H4N)(CO)(PPh3)2]. The addition of [Au(C6F5)(tht)] (tht =
      tetrahydrothiophene) resulted in the formation of [Ru(CH?CHC6H4F
      4){O2CC5H4N(AuC6F5)}(CO)(PPh3)2]. Similarly, [Ru(vinyl)(O2CC6H4CN-4)(CO)(PPh3)2]
      reacted with [Au(C6F5)(tht)] to provide [Ru(vinyl){O2CC6H4(CNAuC6F5)
      4}(CO)(PPh3)2]. The reaction of 4-cyanobenzoic acid with [Au(C6F5)(tht)] yielded
      [Au(C6F5)(NCC6H4CO2H-4)]. This compound was used to prepare [Ru(CH?CHC6H4F
      4){O2CC6H4(CNAuC6F5)-4}(CO)(PPh3)2], which was also formed on treatment of
      [Ru(CH?CHC6H4F-4)(O2CC6H4CN-4)(CO)(PPh3)2] with [Au(C6F5)(tht)]. The known
      compound [RhCl2(NC5H4CO2)(NC5H4CO2Na)3] and the new complex [RhCl2{NC5H4(C6H4CO2)
      4}{NC5H4(C6H4CO2Na)-4}3] were prepared from RhCl3.3H2O and isonicotinic acid or 4
      (4-pyridyl)benzoic acid, respectively. The former was treated with
      [Ru(CH?CHC6H4Me-4)Cl(CO)(BTD)(PPh3)2] to yield [RhCl2{NC5H4CO2(Ru(CH?CHC6H4Me
      4)(CO)(PPh3)2}4]Cl. As an alternative route to pentametallic compounds, the Pd
      coordinated porphyrin [(Pd-TPP)(p-CO2H)4] was treated with 4 equiv of
      [Ru(CH?CHR)Cl(CO)(BTD)(PPh3)2] in the presence of a base to yield [(Pd-TPP){p
      CO2Ru(CH?CHR)(CO)(PPh3)2}4] (R = C6H4Me-4, CPh2OH). Where R = CPh2OH, treatment
      with HBF4 led to the formation of [(Pd-TPP){p
      CO2Ru(?CHCH?CPh2)(CO)(PPh3)2}4](BF4)4. [(Pd-TPP){p-CO2Ru(dppm)2}4](PF6)4 was
      prepared from [(Pd-TPP)(p-CO2H)4] and cis-[RuCl2(dppm)2]. The reaction of AgNO3
      with sodium borohydride in the presence of [Ru(O2CC5H4N)(dppm)2](+) or
      [RuR{O2CC6H4(C5H4N)-4}(dppm)2](+) provided silver nanoparticles
      Ag@[NC5H4CO2Ru(dppm)2](+) and Ag@[NC5H4{C6H4CO2Ru(dppm)2}-4](+).

PMID- 23547653
TI  - Stepwise transformation of the molecular building blocks in a porphyrin
      encapsulating metal-organic material.
AB  - When immersed in solutions containing Cu(II) cations, the microporous metal
      organic material P11 ([Cd4(BPT)4].[Cd(C44H36N8)(S)].[S], BPT = biphenyl-3,4',5
      tricarboxylate) undergoes a transformation of its [Cd2(COO)6](2-) molecular
      building blocks (MBBs) into novel tetranuclear [Cu4X2(COO)6(S)2] MBBs to form P11
      Cu. The transformation occurs in single-crystal to single-crystal fashion, and
      its stepwise mechanism was studied by varying the Cd(2+)/Cu(2+) ratio of the
      solution in which crystals of P11 were immersed. P11-16/1 (Cd in framework
      retained, Cd in encapsulated porphyrins exchanged) and other intermediate phases
      were thereby isolated and structurally characterized. P11-16/1 and P11-Cu retain
      the microporosity of P11, and the relatively larger MBBs in P11-Cu permit a 20%
      unit cell expansion and afford a higher surface area and a larger pore size.

PMID- 23547652
TI  - 3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone
      deacetylase inhibition.
AB  - Small molecules bearing hydroxamic acid as the zinc binding group (ZBG) have been
      the most effective histone deacetylase inhibitors (HDACi) to date. However,
      concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety have
      stimulated research efforts aimed at finding alternative nonhydroxamate ZBGs. We
      have identified 3-hydroxypyridin-2-thione (3-HPT) as a novel ZBG that is
      compatible with HDAC inhibition. 3-HPT inhibits HDAC 6 and HDAC 8 with an IC50 of
      681 and 3675 nM, respectively. Remarkably, 3-HPT gives no inhibition of HDAC 1.
      Subsequent optimization led to several novel 3HPT-based HDACi that are selective
      for HDAC 6 and HDAC 8. Furthermore, a subset of these inhibitors induces
      apoptosis in various cancer cell lines.

PMID- 23547654
TI  - Development of a patient-centred care pathway across healthcare providers: a
      qualitative study.
AB  - BACKGROUND: Different models for care pathways involving both specialist and
      primary care have been developed to ensure adequate follow-up after discharge.
      These care pathways have mainly been developed and run by specialist care and
      have been disease-based. In this study, primary care providers took the
      initiative to develop a model for integrated care pathways across care levels for
      older patients in need of home care services after discharge. Initially, the
      objective was to develop pathways for patients diagnosed with heart failure, COPD
      and stroke. The aim of this paper is to investigate the process and the
      experiences of the participants in this developmental work. The participants were
      drawn from three hospitals, six municipalities and patient organizations in
      Central Norway. METHODS: This qualitative study used focus group interviews,
      written material and observations. Representatives from the hospitals,
      municipalities and patient organizations taking part in the development process
      were chosen as informants. RESULTS: The development process was very challenging
      because of the differing perspectives on care and different organizational
      structures in specialist care and primary care. In this study, the disease
      perspective, being dominant in specialist care, was not found to be suitable for
      use in primary health care because of the need to cover a broader perspective
      including the patient's functioning, social situation and his or her preferences.
      Furthermore, managing several different disease-based care pathways was found to
      be unsuitable in home care services, as well as unsuitable for a population
      characterized by a substantial degree of comorbidity. The outcome of the
      development process was a consensus that outlined a single, common patient
      centred care pathway for transition from hospital to follow-up in primary care.
      The pathway was suitable for most common diseases and included functional and
      social aspects as well as disease follow-up, thus merging the differing
      perspectives. The disease-based care pathways were kept for use within the
      hospitals. CONCLUSIONS: Disease-based care pathways for older patients were found
      to be neither feasible nor sustainable in primary care. A common patient-centred
      care pathway that could meet the needs of multi- morbid patients was recommended.

PMID- 23547656
TI  - Cytogenetic analysis in three Bryconamericus species (Characiformes, Characidae):
      first description of the 5S rDNA-bearing chromosome pairs in the genus.
AB  - BACKGROUND: Nowadays, the genus Bryconamericus is placed in subfamily
      Stevardiinae within of Characidae, but not shows consistent evidence of
      monophyletism. The purpose of this work was to study the chromosomes of three
      species of Bryconamericus, aiming to add cytogenetic knowledge and contribute to
      the understanding of the chromosomal evolution of this genus. RESULTS: The
      chromosomes of three species of Bryconamericus were analyzed using cytogenetic
      techniques. The karyotype of Bryconamericus stramineus contained 6 metacentric
      (m) + 10 submetacentric (sm) + 16 subtelocentric (st) + 20 acrocentric (a), the
      fundamental number (FN) of 84, one silver impregnated (Ag-NOR) pair, one pair
      bearing the 18S ribosomal DNA sites, another pair bearing the 5S rDNA sites, and
      a few positive C-bands. Bryconamericus turiuba had a karyotype containing 8 m +
      10sm + 14st + 20a (FN = 84), one chromosome pair Ag-NOR, two pairs bearing the
      18S rDNA sites, two pairs bearing the 5S rDNA sites, and a few C-band regions.
      Bryconamericus cf. iheringii had a karyotype containing 10 m + 14sm + 18st + 10a
      (FN = 94), including one pair with a secondary constriction Ag-NOR positive. In
      this karyotype the fluorescent in situ hybridization (FISH) showed the 18S and 5S
      rDNA probe in adjacent position. CONCLUSIONS: The results obtained in this work
      showed different characteristics in the organization of two multigene families,
      indicating that distinct evolutionary forces acting on the diversity of rDNA
      sequences in the genome of three Bryconamericus species.

PMID- 23547655
TI  - Rapid initial decline in BCR-ABL1 is associated with superior responses to second
      line nilotinib in patients with chronic-phase chronic myeloid leukemia.
AB  - BACKGROUND: We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and
      analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be
      used to predict long-term responses. METHODS: Patients from the nilotinib
      registration trial (CAMN107A2101; registered at http://www.clinicaltrials.gov as
      NCT00109707) who had imatinib-resistant or -intolerant Philadelphia chromosome
      positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) or
      accelerated phase with BCR-ABL1 > 10% (on the international scale [IS]) at
      baseline and, in the first 6 months, had at least three BCR-ABL1 transcript
      measurements and an average daily dose of at least 720 mg were included in this
      analysis (N = 123). RESULTS: More than half of patients (65/123; 53%) had a slow
      monophasic response and the remainder (58/123; 47%) had a biphasic response, in
      which patients had a rapid initial decrease in BCR-ABL1 transcripts followed by a
      more gradual response. The biphasic response type strongly correlated with
      improved event-free survival (EFS). Data in the first 6 months of follow-up were
      sufficient to predict EFS at 24 months. CONCLUSIONS: Unlike newly diagnosed
      patients with Ph+ CML-CP-in whom the majority had a biphasic response
      approximately half of patients with imatinib-resistant or -intolerant CML had a
      slower, monophasic response. Second-line patients who did have a biphasic
      response had an EFS outlook similar to that of newly diagnosed patients treated
      with imatinib. Our model was comparable to using BCR-ABL1 (IS) <= 10% at 6 months
      as a threshold for predicting EFS.

PMID- 23547657
TI  - Energy status of ripening and postharvest senescent fruit of litchi (Litchi
      chinensis Sonn.).
AB  - BACKGROUND: Recent studies have demonstrated that cellular energy is a key factor
      switching on ripening and senescence of fruit. However, the factors that
      influence fruit energy status remain largely unknown. RESULTS: HPLC profiling
      showed that ATP abundance increased significantly in developing preharvest litchi
      fruit and was strongly correlated with fruit fresh weight. In contrast, ATP
      levels declined significantly during postharvest fruit senescence and were
      correlated with the decrease in the proportion of edible fruit. The five gene
      transcripts isolated from the litchi fruit pericarp were highly expressed in
      vegetative tissues and peaked at 70 days after flowering (DAF) consistent with
      fruit ADP concentrations, except for uncoupling mitochondrial protein 1 (UCP1),
      which was predominantly expressed in the root, and ATP synthase beta subunit
      (AtpB), which was up-regulated significantly before harvest and peaked 2 days
      after storage. These results indicated that the color-breaker stage at 70 DAF and
      2 days after storage may be key turning points in fruit energy metabolism.
      Transcript abundance of alternative oxidase 1 (AOX1) increased after 2 days of
      storage to significantly higher levels than those of LcAtpB, and was down
      regulated significantly by exogenous ATP. ATP supplementation had no significant
      effect on transcript abundance of ADP/ATP carrier 1 (AAC1) and slowed the changes
      in sucrose non-fermenting-1-related kinase 2 (SnRK2) expression, but maintained
      ATP and energy charge levels, which were correlated with delayed senescence.
      CONCLUSIONS: Our results suggest that senescence of litchi fruit is closely
      related with energy. A surge of LcAtpB expression marked the beginning of fruit
      senescence. The findings may provide a new strategy to extend fruit shelf life by
      regulating its energy level.

PMID- 23547658
TI  - Thyroid hormone-induced cell-cell interactions are required for the development
      of adult intestinal stem cells.
AB  - The mammalian intestine has long been used as a model to study organ-specific
      adult stem cells, which are essential for organ repair and tissue regeneration
      throughout adult life. The establishment of the intestinal epithelial cell self
      renewing system takes place during perinatal development when the villus-crypt
      axis is established with the adult stem cells localized in the crypt. This
      developmental period is characterized by high levels of plasma thyroid hormone
      (T3) and T3 deficiency is known to impair intestinal development. Determining how
      T3 regulates adult stem cell development in the mammalian intestine can be
      difficult due to maternal influences. Intestinal remodeling during amphibian
      metamorphosis resembles perinatal intestinal maturation in mammals and its
      dependence on T3 is well established. A major advantage of the amphibian model is
      that it can easily be controlled by altering the availability of T3. The ability
      to manipulate and examine this relatively rapid and localized formation of adult
      stem cells has greatly assisted in the elucidation of molecular mechanisms
      regulating their formation and further revealed evidence that supports
      conservation in the underlying mechanisms of adult stem cell development in
      vertebrates. Furthermore, genetic studies in Xenopus laevis indicate that T3
      actions in both the epithelium and the rest of the intestine, most likely the
      underlying connective tissue, are required for the formation of adult stem cells.
      Molecular analyses suggest that cell-cell interactions involving hedgehog and BMP
      pathways are critical for the establishment of the stem cell niche that is
      essential for the formation of the adult intestinal stem cells.

PMID- 23547659
TI  - Chondrocyte density, proteoglycan content and gene expressions from native
      cartilage are species specific and not dependent on cartilage thickness: a
      comparative analysis between rat, rabbit and goat.
AB  - BACKGROUND: In many pre-clinical studies of cartilage tissue, it has been
      generally assumed that the major difference of the tissue between the species is
      the tissue thickness, which is related to the size of the animal itself. At
      present, there appear to be lack of studies demonstrating the relationship
      between chondrocyte densities, protein content, gene expressions and cartilage
      thickness in the various animal models that are commonly used. The present study
      was conducted to determine whether or not chondrocyte density,
      proteoglycan/protein content and selective chondrocyte gene expression are merely
      related to the cartilage thickness (thus animal size), and not the intrinsic
      nature of the species being investigated. Mature animals (rabbit, rats and goats)
      were sacrificed for their hind knee cartilages. Image analyses were performed on
      five consecutive histological sections, sampled from three pre-defined locations
      at the lateral and medial femoral condyles. Cartilage thickness, chondrocyte
      density, Glycosaminoglycan (GAGs)/protein content and gene expression levels for
      collagen II and SOX-9 were compared across the groups. Correlation analysis was
      done between cartilage thickness and the other variables. RESULTS: The mean
      cartilage thickness of rats, rabbits and goats were 166.5 +/- 10.9, 356.2 +/-
      25.0 907.5 +/- 114.6 MUm, respectively. The mean cartilage cell densities were
      3.3 +/- 0.4*10(-3) for rats, 2.6 +/- 0.3*10(-3) for rabbits and 1.3 +/- 0.2*10(
      3) cells/MUm2 for goats. The mean MUg GAG/mg protein content were 23.8 +/- 8.6 in
      rats, 20.5 +/- 5.3 in rabbits and 328.7 +/- 64.5 in goats; collagen II gene
      expressions were increased by 0.5 +/- 0.1 folds in rats; 0.6 +/- 0.1 folds in
      rabbits, and 0.1 +/- 0.1 folds in goats, whilst the fold increase of SOX-9 gene
      expression was 0.5 +/- 0.1 in rats, 0.7 +/- 0.1 in rabbits and 0.1 +/- 0.0 in
      goats. Cartilage thickness correlated positively with animals' weight (R2
      =0.9856, p = 0.001) and GAG/protein content (R2 =0.6163, p = <0.001). Whereas, it
      correlates negatively with cell density (R2 = 0.7981, p < 0.001) and cartilage
      gene expression levels (R2 = 0.6395, p < 0.001). CONCLUSION: There are
      differences in the composition of the articular cartilage in diverse species,
      which are not directly dependent on the cartilage thickness of these animals but
      rather the unique characteristics of that species. Therefore, the species
      specific nature of the cartilage tissue should be considered during any data
      interpretation.

PMID- 23547660
TI  - The Tiotropium Safety and Performance in Respimat Trial (TIOSPIR), a large scale,
      randomized, controlled, parallel-group trial-design and rationale.
AB  - BACKGROUND: Tiotropium bromide is an effective therapy for COPD patients.
      Comparing across programs tiotropium Respimat Soft Mist inhaler was at least as
      efficacious as tiotropium HandiHaler, however, concerns have been raised about
      tiotropium's safety when given via Respimat. METHODS: The TIOSPIR trial
      (NCT01126437) compares the safety and efficacy of tiotropium Respimat 5 MUg once
      daily (marketed) and 2.5 MUg once daily (investigational) with tiotropium
      HandiHaler 18 MU once daily (marketed). The hypotheses to be tested are 1). that
      tiotropium Respimat 5 MUg once daily and Respimat 2.5 MUg once daily are non
      inferior to HandiHaler in terms of all-cause mortality, and 2). that tiotropium
      Respimat 5 MUg once daily is superior to HandiHaler in terms of time to first
      exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The
      trial is a randomized, double-blind, double dummy, event-driven, parallel group
      study. Participants can use any background treatment for COPD except inhaled
      anticholinergic agents. The study encompasses a wide range of COPD patients, e.g.
      patients with stable cardiac diseases including arrhythmia can be included.
      Clinical sites are international and include both primary care as well as
      specialists. RESULTS: To date, over 17,000 participants have been randomized from
      over 1200 sites in 50 countries with an anticipated treatment duration of 2-3
      years. CONCLUSION: TIOSPIR will provide precise estimates of the relative safety
      and efficacy of the Respimat and HandiHaler formulations of tiotropium, assess
      potential dose-dependence of important outcomes and provide information on the
      clinical epidemiology of COPD in a large international patient cohort.

PMID- 23547661
TI  - Response to intervention in secondary settings: speech-language pathologists'
      perspectives.
AB  - This study explored the reactions of 44 speech-language pathologists (SLPs) to
      Response to Intervention (RTI) in secondary settings. Respondents were part of a
      random sample of SLPs from across the US. A mixed-methods approach included
      quantitative data from a questionnaire containing 47 Likert-type items and
      qualitative findings from responses to an open-ended question. Results revealed
      participants value the model but recognize educators face challenges in
      implementation. Qualitative findings revealed four themes: (a) challenges and
      concerns, (b) support for the model, (c) implementation considerations, and (d)
      role of SLPs. Findings suggest that administrators and educators need to
      collaborate more closely in order to effectively implement RTI in secondary
      settings.

PMID- 23547663
TI  - A library of livestock heritage: a private foundation works to preserve rare
      ruminant breeds.

PMID- 23547664
TI  - Comments on homeopathy resolution.

PMID- 23547665
TI  - A short history of veterinary workforce analyses.

PMID- 23547666
TI  - Laboratory animals as veterinary patients.

PMID- 23547667
TI  - What is your diagnosis? Low-grade myxosarcoma arising from the heart valve.

PMID- 23547668
TI  - Animal behavior case of the month. Underlying anxiety disorder in an aggressive
      dog.

PMID- 23547669
TI  - Pathology in practice. Soft tissue abscesses and vertebral osteomyelitis
      attributable to N farcinica infection in 2 calves.

PMID- 23547670
TI  - Pathology in practice. Cryptococcal osteomyelitis in a dog.

PMID- 23547671
TI  - Facebook use among early-career veterinarians in Ontario, Canada (March to May
      2010).
AB  - OBJECTIVE: To explore the nature and content of information publicly posted to
      Facebook by early-career veterinarians. DESIGN: Cross-sectional descriptive
      study. Sample-352 early-career veterinarians. PROCEDURES: Publicly accessible
      Facebook profiles were searched online from March to May 2010 for profiles of
      early-career veterinarians (graduates from 2004 through 2009) registered with the
      College of Veterinarians of Ontario, Canada. The content of veterinarians'
      Facebook profiles was evaluated and then categorized as low, medium, or high
      exposure in terms of the information a veterinarian had publicly posted to
      Facebook. Through the use of content analysis, high-exposure profiles were
      further analyzed for publicly posted information that may have posed risks to an
      individual's or the profession's public image. RESULTS: Facebook profiles for 352
      of 494 (71%) registered early-career veterinarians were located. One-quarter
      (25%) of profiles were categorized as low exposure (ie, high privacy), over half
      (54%) as medium exposure (i.e., medium privacy), and 21% as high exposure (i.e.,
      low privacy). Content analysis of the high-exposure profiles identified publicly
      posted information that may pose risks to an individual's or the profession's
      reputation, including breaches of client confidentiality, evidence of substance
      abuse, and demeaning comments toward others. CONCLUSIONS AND CLINICAL RELEVANCE:
      Almost a quarter of veterinarians' Facebook profiles viewed in the present study
      contained publicly available content of a questionable nature that could pose a
      risk to the reputation of the individual, his or her practice, or the veterinary
      profession. The increased use of Facebook and all types of social media points to
      the need for raised awareness by veterinarians of all ages of how to manage one's
      personal and professional identities online to minimize reputation risks for
      individuals and their practices and to protect the reputation and integrity of
      the veterinary profession.

PMID- 23547672
TI  - Safety and efficacy of spinosad chewable tablets for treatment of flea
      infestations of cats.
AB  - OBJECTIVE: To compare safety and efficacy of spinosad and selamectin and
      determine effects of those products on flea allergy dermatitis (FAD) in cats.
      DESIGN: Randomized clinical trial. Animals-211 client-owned cats. PROCEDURES:
      Cats with >= 5 fleas evaluated at 8 veterinary clinics were allocated to receive
      spinosad (50 to 100 mg/kg [22.7 to 45.5 mg/lb], PO; n = 139) or selamectin (>= 6
      mg/kg [>= 2.7 mg/lb], topically; 72) once per month. Flea comb counts and FAD
      scores were determined on day -1, between days 27 and 33, and between days 85 and
      95 (evaluations 1, 2, and 3, respectively); day 0 was the first day of drug
      administration. RESULTS: The most common adverse event was vomiting (14.3% and
      2.4% of spinosad- and selamectin-treated cats, respectively). Evaluation 2 and 3
      geometric mean flea counts for spinosad-treated cats were significantly lower
      than those for selamectin-treated cats. Percentage reductions in flea counts for
      the spinosad and selamectin groups were 97.5% and 88.8% (evaluation 2) and 99.3%
      and 97.7% (evaluation 3), respectively. At evaluations 2 and 3, 70.6% and 92.6%
      of spinosad-treated cats and 29.4% and 64.7% of selamectin-treated cats were free
      of fleas, respectively. Weighted FAD scores for spinosad- and selamectin-treated
      cats decreased 94.2% and 80.0% during the study, respectively. Spinosad tablets
      were successfully administered during 98.1% of treatments. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results of this study indicated spinosad and selamectin both
      reduced flea counts and FAD scores for cats, although spinosad was more
      effective. Monthly oral administration of spinosad may be practical for treatment
      of flea infestations and FAD in cats.

PMID- 23547673
TI  - Epidemiological evaluation of cystine urolithiasis in domestic ferrets (Mustela
      putorius furo): 70 cases (1992-2009).
AB  - OBJECTIVE: To determine the prevalence of cystine uroliths in domestic ferrets
      with urolithiasis and determine whether age, breed, sex, reproductive status,
      anatomic location, and season are risk factors associated with cystine urolith
      formation. DESIGN: Retrospective cross-sectional case-control study. SAMPLE:
      Records of 435 ferrets (Mustela putorius furo) with uroliths submitted for
      analyses between 1992 and 2009, of which 70 were cystine uroliths. PROCEDURES:
      Specific descriptive information was obtained about each ferret to determine
      whether specific risk factors were associated with the development of cystine
      uroliths. RESULTS: Cystine uroliths comprised 70 of the 435 (16%) uroliths.
      Cystine uroliths were more common in male (n = 54) than in female (16) ferrets.
      All cystine uroliths were retrieved from the lower portion of the urinary tract
      (bladder and urethra [n = 67]) or were voided (3); none of the uroliths were
      retrieved from the upper portion of the urinary tract (kidney and ureters).
      CONCLUSIONS AND CLINICAL RELEVANCE: Awareness of the prevalence of cystine
      uroliths along with knowledge of etiologic, demographic, and environmental risk
      and protective factors for urolithiasis may facilitate development of
      surveillance strategies that result in earlier detection of cystinuria. Genetic
      factors associated with this disease have not yet been reported in ferrets, but a
      familial pattern of inheritance determined to be a major underlying factor in
      cystine urolithiasis in dogs and humans suggests that this may be a factor in
      ferrets and that the parent stock of ferrets in the present study may have been
      inbred.

PMID- 23547674
TI  - Lymphoma in cats treated with a weekly cyclophosphamide-, vincristine-, and
      prednisone-based protocol: 114 cases (1998-2008).
AB  - OBJECTIVE: To evaluate the clinical response rate, progression-free survival
      time, overall survival time, and possible prognostic factors associated with a
      cyclophosphamide-, vincristine-, and prednisone (COP)-based chemotherapy protocol
      in cats with lymphoma. DESIGN: Retrospective case series. ANIMALS: 114 cats with
      lymphoma. PROCEDURES: Medical records of cats receiving a weekly COP-based
      chemotherapy protocol from 1998 to 2008 at the Matthew J. Ryan Veterinary
      Hospital of the University of Pennsylvania were evaluated for information
      regarding signalment, anatomic site of involvement, cell morphology, treatment,
      and outcome. Retroviral status, baseline weight, substage, anatomic location,
      dose delays, dose reductions, and response to treatment were evaluated for
      prognostic importance. RESULTS: The majority of cases (94 [82.4%]) were substage
      b, and the most common anatomic site was the gastrointestinal tract (57 [50%]).
      Clinical response rate after the first chemotherapy cycle was 47.4%. Response to
      treatment was significantly associated with progression-free survival time and
      overall survival time, whereas substage was significantly associated with
      progression-free survival time. The median progression-free survival time and
      overall survival time were 65.5 and 108 days, respectively. Compared with
      nonresponders, responders had significantly longer median progression-free
      survival time (364 vs 31 days) and median overall survival time (591 vs 73 days).
      CONCLUSIONS AND CLINICAL RELEVANCE: Clinical response after 1 cycle of COP-based
      chemotherapy was predictive for progression-free survival time and overall
      survival time in cats with lymphoma; therefore, response after 1 cycle of
      chemotherapy could be used to guide decisions about further treatment. No new
      prognostic factors were identified.

PMID- 23547675
TI  - Outcome following gastrointestinal tract decontamination and intravenous fluid
      diuresis in cats with known lily ingestion: 25 cases (2001-2010).
AB  - OBJECTIVE: To describe the outcome of cats treated with gastrointestinal tract
      decontamination, IV fluid diuresis, or both after ingestion of plant material
      from lilies of the Lilium and Hemerocallis genera. Design-Retrospective case
      series. ANIMALS: 25 cats evaluated after ingestion of lily plants. PROCEDURES:
      Medical records of cats examined at the Matthew J. Ryan Veterinary Hospital of
      the University of Pennsylvania with known lily ingestion between July 2001 and
      April 2010 were reviewed. Inclusion in the study required evidence of lily plant
      ingestion within the preceding 48 hours. Type of lily ingested, time of
      ingestion, gastrointestinal tract decontamination procedures performed, and IV
      fluid diuresis were recorded. The presence or absence of acute kidney injury was
      determined by evaluating BUN concentration, creatinine concentration, and urine
      specific gravity. Outcome was defined as survival to discharge, death, or
      euthanasia. RESULTS: The time from ingestion until evaluation at the Matthew J.
      Ryan Veterinary Hospital of the University of Pennsylvania ranged from < 30
      minutes to 48 hours. Nineteen cats received gastrointestinal tract
      decontamination (18 cats at our hospital and 1 cat by the referring
      veterinarian). Twenty-three cats were admitted to the hospital for IV fluid
      diuresis, supportive care, and monitoring. Seventeen of these 23 (74%) cats had
      normal BUN and creatinine concentrations throughout hospitalization. At the time
      of discharge from the hospital, 2 of the 23 (9%) hospitalized cats had an
      increased BUN concentration, creatinine concentration, or both. All 25 (100%)
      cats survived to discharge from the hospital. CONCLUSIONS AND CLINICAL RELEVANCE:
      In this series of cats treated with gastrointestinal tract decontamination, IV
      fluid diuresis, or both within 48 hours after lily ingestion, the outcome was
      good, with a low incidence of acute kidney injury. Future studies are needed to
      determine the most effective gastrointestinal tract decontamination procedures
      and optimal duration of IV fluid therapy.

PMID- 23547676
TI  - Treatment of traumatic penile urethral stricture in a dog with a self-expanding,
      covered nitinol stent.
AB  - CASE DESCRIPTION: An 8-month-old castrated male mixed-breed dog was evaluated
      because of hematuria, stranguria, and dysuria of approximately 2 weeks' duration
      that developed immediately following elective castration. CLINICAL FINDINGS:
      Results of physical examination, ultrasonography, retrograde double-contrast
      cystourethrography, and urethroscopy were consistent with a traumatic urethral
      stricture immediately proximal to the os penis resulting in a partial obstruction
      of urine outflow. Results of ultrasonographic examination of abdominal organs
      were considered normal. Digital radiography revealed no evidence of calculi.
      TREATMENT AND OUTCOME: Balloon dilation of the urethral stricture was performed
      and was followed by 2 bougienage procedures during the subsequent 2 weeks when
      clinical signs returned. The owners declined scrotal urethrostomy, and a self
      expanding, covered nitinol stent was placed approximately 3 weeks after the
      initial evaluation, resulting in amelioration of clinical signs. Results of
      follow-up urethroscopy and contrast cystourethrography 1 year after stent
      placement revealed a statically positioned, patent urethral stent, although a
      small number of polypoid mucosal structures were identified distal to the stent
      and 1 small structure consistent with tissue ingrowth into the stent was
      identified. CLINICAL RELEVANCE: Placement of a covered nitinol stent resulted in
      long-term resolution of clinical signs associated with traumatic stricture of the
      penile urethra in this young dog. Because the os penis in dogs limits radial
      expansion of the urethra, its presence may limit the use of stents in this
      location.

PMID- 23547677
TI  - Diagnosis and treatment of proventricular nematodiasis in an umbrella cockatoo
      (Cacatua alba).
AB  - CASE DESCRIPTION: A 16-year-old female umbrella cockatoo (Cacatua alba) was
      referred to the University of Georgia College of Veterinary Medicine for
      evaluation of a 3-year seasonal history of lethargy and weight fluctuation.
      CLINICAL FINDINGS: Abnormalities detected via clinicopathologic analyses included
      mild leukocytosis, heterophilia, and lymphopenia consistent with a stress
      leukogram. Previous fecal examinations failed to diagnose enteric parasite
      infestation. Results of a fecal flotation test with Sheather sugar solution
      revealed spirurid eggs (Spiruroidea). Coelomic radiography revealed a widened
      cardiohepatic waist with increased soft tissue opacity at the level of the
      hepatic silhouette. The caudal thoracic and abdominal air sacs bilaterally
      appeared compressed against the coleomic wall. The proventriculus was increased
      in diameter, with a proventriculus-to-keel ratio of 1.0. Coelomic ultrasonography
      and positive-contrast upper gastrointestinal radiography revealed severe
      thickening and irregularity of the proventricular wall. The animal was
      anesthetized for an endoscopic examination of the upper gastrointestinal tract.
      Intralesional nematodes were identified on histologic examination of biopsy
      specimens from the proventriculus. TREATMENT AND OUTCOME: Effective fenbendazole
      treatment (15 mg/kg [6.8 mg/lb], PO, alternating between 5 days of treatment and
      5 days of no treatment, which continued for 4 periods) was confirmed by repeated
      endoscopy and fecal examinations. The bird remained free of clinical signs 27
      months after diagnosis and treatment. CLINICAL RELEVANCE: Antemortem diagnosis of
      proventricular nematodiasis has not been reported in psittacines. Spirurid
      nematode eggs are shed intermittently, which may lead to false-negative results
      on a single routine fecal examination. In this patient, radiography, endoscopy,
      and histologic evaluation facilitated antemortem diagnosis. This is the first
      report of successful treatment of this condition in psittacines.

PMID- 23547678
TI  - Histopathologic findings in the sacrocaudalis dorsalis medialis muscle of horses
      with vitamin E-responsive muscle atrophy and weakness.
AB  - OBJECTIVE: To characterize clinical findings, outcomes, muscle characteristics,
      and serum or muscle concentrations of alpha-tocopherol for horses with vitamin E
      responsive signs of muscle atrophy and weakness consistent with signs of equine
      motor neuron disease (EMND). DESIGN: Retrospective case-control study. ANIMALS: 8
      affected (case) adult horses with acute (n = 3) or chronic (5) gross muscle
      atrophy that improved with vitamin E treatment and 14 clinically normal (control)
      adult horses with adequate (within reference range; 8) or low (6) muscle
      concentrations of alpha-tocopherol. PROCEDURES: Medical records were reviewed,
      serum and muscle concentrations of alpha-tocopherol were measured, and frozen
      biopsy specimens of sacrocaudalis dorsalis medialis muscle and gluteal muscle
      were histologically evaluated for pathological changes. Fiber type composition
      and fiber diameters were assessed in gluteal muscle specimens. RESULTS: A
      myopathy that was histologically characterized by redistribution of mitochondrial
      enzyme stain (moth-eaten appearance) and anguloid atrophy of myofibers was
      evident in sacrocaudalis dorsalis medialis muscle fibers of the 8 affected horses
      that had low serum (6/8) or skeletal muscle (5/5) concentrations of alpha
      tocopherol; these histopathologic changes were not found in muscle specimens of
      control horses with low or adequate muscle concentrations of alpha-tocopherol.
      All affected horses regained strength and muscle mass within 3 months after
      initiation of vitamin E treatment and dietary changes. CONCLUSIONS AND CLINICAL
      RELEVANCE: A vitamin E-deficient myopathy characterized histologically by a moth
      eaten appearance in the mitochondria and anguloid myofiber atrophy in frozen
      sections of sacrocaudalis dorsalis medialis muscle biopsy specimens was found in
      horses with clinical signs of EMND that were highly responsive to vitamin E
      treatment. This myopathy may be a specific syndrome or possibly precede the
      development of neurogenic muscle fiber atrophy typical of EMND.

PMID- 23547679
TI  - Clinical and diagnostic features of inflammatory airway disease subtypes in
      horses examined because of poor performance: 98 cases (2004-2010).
AB  - OBJECTIVE: To determine whether there are important differences relating to
      seasonality of signs or clinical features between subtypes of inflammatory airway
      disease (IAD) in horses caused by neutrophilic and eosinophilic-mastocytic
      inflammation having dissimilar etiopathologic pathways. DESIGN: Retrospective
      case series. ANIMALS: 98 horses. PROCEDURES: Data were compiled from medical
      records of horses examined because of poor performance from 2004 through 2010.
      Horses underwent a standardized high-speed treadmill test, lameness evaluation,
      cardiac evaluation, and postexercise bronchoalveolar lavage (BAL). By means of
      standard BAL cytologic criteria, horses were divided into 4 groups: eosinophilic
      mastocytic inflammation, neutrophilia only, mixed inflammation, or no
      inflammation (control). Associations between IAD subtype and clinical parameters
      were investigated. RESULTS: Data for 98 horses were obtained, including age,
      career, season of admission, and results of hematologic evaluation, high-speed
      treadmill arterial blood gas analysis, upper airway endoscopy, cardiologic
      evaluation, and BAL. Cytologic evidence of IAD was found in 81% (79/98) of the
      horses, and 30% (30/98) had erythrocytes present in the BAL fluid after exercise.
      Horses in the eosinophilic-mastocytic inflammation and mixed-inflammation groups
      were significantly more likely to be Thoroughbred than Standardbred and have
      larger amounts of mucus in their BAL fluid. No significant differences were found
      in season of evaluation, results of exercising blood gas analyses, or
      comorbidities. CONCLUSIONS AND CLINICAL RELEVANCE: No association between season
      and cytologic profile of BAL fluid and no major effects of IAD subtype on
      pulmonary gas exchange during exercise were seen in this population of horses.

PMID- 23547680
TI  - Comparison of phenylephrine administration and exercise versus phenylephrine
      administration and a rolling procedure for the correction of nephrosplenic
      entrapment of the large colon in horses: 88 cases (2004-2010).
AB  - OBJECTIVE: To compare the outcome of horses with nephrosplenic entrapment of the
      large colon (NSELC) that were treated nonsurgically by IV administration of
      phenylephrine and exercise with that of horses treated by IV administration of
      phenylephrine and a rolling procedure under general anesthesia. DESIGN:
      Retrospective case series. ANIMALS: 88 horses with NSELC. PROCEDURES: Horses
      examined between 2004 and 2010 because of acute abdominal pain that had NSELC on
      the basis of findings on abdominal palpation per rectum, abdominal
      ultrasonography, or both were included. Medical records were reviewed to obtain
      information on treatment (IV administration of phenylephrine and exercise vs IV
      administration of phenylephrine and a rolling procedure) and outcome. RESULTS:
      Overall, 85% (75/88) of horses with NSELC responded to exercise or rolling under
      general anesthesia. The success rate of rolling under general anesthesia (42/50
      [84%]) was significantly higher than the success rate of exercise after IV
      administration of phenylephrine (24/38 [63.2%]). Resolution of NSELC was achieved
      by rolling under general anesthesia in 8 of 14 horses that initially failed to
      resolve with exercise. CONCLUSIONS AND CLINICAL RELEVANCE: A rolling procedure
      performed under general anesthesia had a higher success rate than exercise after
      IV phenylephrine administration for resolution of NSELC in horses, suggesting
      that rolling could be considered as the initial medical treatment. The rolling
      procedure may be labor intensive and should only be attempted in a surgical
      facility in the event that exploratory laparotomy is required.

PMID- 23547681
TI  - Enthesopathy and desmitis of the medial collateral ligament of the cubital joint
      in 4 horses.
AB  - CASE DESCRIPTION: 4 horses with enthesopathy and desmitis of the medial
      collateral ligament of the cubital joint were examined. CLINICAL FINDINGS: All 4
      horses had a history of acute, severe, unilateral forelimb lameness and had signs
      of pain during manipulation of the affected upper forelimb; 2 also had swelling
      in the axillary region. There was no improvement in lameness after diagnostic
      local analgesia below the carpal region, and 1 of 4 horses had mild improvement
      after cubital joint analgesia. Radiography revealed enthesophyte formation on the
      radial tuberosity and linear mineralization of the medial collateral ligament in
      2 horses and periosteal reaction on the humeral condyle in all 4 horses. One
      horse had mild osteoarthritis of the cubital joint, and 3 had osteophytosis of
      the cranial aspect of the radius. Although all horses were initially examined
      because of an acute onset of lameness, all had chronic abnormalities visible on
      imaging. Ultrasonography revealed an irregular boney contour and enthesopathy at
      the insertion of the short medial collateral ligament to the radial tuberosity
      and desmitis of the short medial collateral ligament. Two horses had radiographic
      evidence of similar but less severe lesions of the contralateral cubital joint.
      TREATMENT AND OUTCOME: All horses received phenylbutazone and rest. All horses
      were free of lameness after a median of 3 months (range, 2 to 4 months) and
      returned to previous use after a median of 6 months (range, 3 to 8 months).
      CONCLUSIONS AND CLINICAL RELEVANCE: The results of the present report suggested
      that performance horses with enthesopathy and desmitis of the medial collateral
      ligament of the cubital joint may have a good prognosis for return to previous
      use following appropriate treatment.

PMID- 23547682
TI  - Synthesis and characterization of nanoparticle thin films of a-(PbSe)100-xCdx
      lead chalcogenides.
AB  - We report the synthesis of amorphous (PbSe)100-xCdx (x = 5, 10, 15, and 20)
      nanoparticle thin films using thermal evaporation method under argon gas
      atmosphere. Thin films with a thickness of 20 nm have been deposited on glass
      substrates at room temperature under a continuous flow (50 sccm) of argon. X-ray
      diffraction patterns suggest the amorphous nature of these thin films. From the
      field emission scanning electron microscopy images, it is observed that these
      thin films contain quite spherical nanoparticles with an average diameter of
      approximately 20 nm. Raman spectra of these a-(PbSe)100-xCdx nanoparticles show a
      wavelength shift in the peak position as compared with earlier reported values on
      PbSe. This shift in peak position may be due to the addition of Cd in PbSe. The
      optical properties of these nanoparticles include the studies on
      photoluminescence and optical constants. On the basis of optical absorption
      measurements, a direct optical bandgap is observed, and the value of the bandgap
      decreases with the increase in metal (Cd) contents in PbSe. Both extinction
      coefficient (k) and refractive index (n) show an increasing trend with the
      increase in Cd concentration. On the basis of temperature dependence of direct
      current conductivity, the activation energy and pre-exponential factor of these
      thin films have been estimated. These calculated values of activation energy and
      pre-exponential factor suggest that the conduction is due to thermally assisted
      tunneling of the carriers.

PMID- 23547683
TI  - Role of sulfur containing amino acids as an adjuvant therapy in the prevention of
      diabetes and its associated complications.
AB  - Amino acid supplementation is gaining acceptance as an important adjuvant therapy
      in the treatment of diabetes and its associated complications. Numerous studies
      in the literature report the impaired amino acid metabolism in diabetes and the
      beneficial effects of amino acids are positively correlated with the increase in
      plasma levels of those amino acids. Oxidative stress is known to play a major
      role in diabetic pathophysiology. Sulfur containing compounds are well known in
      the treatment of oxidative stress induced pathological disorders. Methionine,
      cysteine, and homocysteine are the three common sulfur containing amino acids. In
      addition, taurine, a sulfonic acid containing an amino group (amino sulfonic
      acid), is found in substantial amounts in mammalian tissues. Both experimental
      and clinical studies reported the modulatory effects of cysteine, N-acetyl
      cysteine, or compounds having cysteine moiety in the regulation of insulin
      secretion and plasma glucose levels. Taurine supplementation has been found to
      prevent the onset of diabetes mellitus in experimental models of both insulin
      dependent and insulin independent pathways. Recent reports suggest that the
      beneficial role of cysteine or taurine is mediated via their ability in reducing
      glycooxidation and preventing the generation of intracellular reactive
      intermediates. Studies with methionine or S-adinosyl methionine has been shown to
      increase mitochondrial DNA density in skeletal muscle, improve insulin
      sensitivity and prevent body weight gain. Homocysteine, on the other hand, is an
      emerging risk factor for cardiovascular disease and diabetic patients have higher
      levels of this sulfur containing amino acid. Supplementation with cysteine or
      taurine, however, was found to be effective in reducing plasma homocysteine
      levels. This review will discuss the role of sulfur containing amino acids in the
      regulation of hyperglycemia and in the development of its associated pathological
      dysfunctions.

PMID- 23547685
TI  - Intriguing chemistry of molybdenum corroles.
AB  - The development of new methodologies for gaining access to low-valent molybdenum
      complexes led to spectroscopic identification of mononuclear (oxo)molybdenum(IV)
      corroles, as well as the full characterization of a binuclear molybdenum(IV)
      corrole that is bridged through axial O atoms by a Mg(THF)4 moiety.

PMID- 23547686
TI  - Clever and crude but not kind: narcissism, self-esteem, and the self-reference
      effect.
AB  - According to the agency model of narcissism (Campbell, Brunell, & Finkel, 2006)
      narcissists view themselves as high on agentic traits but low on communal traits.
      To test if this self-view extends to recall, two experiments examined the extent
      to which narcissism was associated with self-ratings and recall of agentic and
      communal traits that varied in valence. Across both experiments a trait
      description task was followed by a surprise recall task for the trait words and
      then completion of the Narcissistic Personality Inventory (NPI; Raskin & Terry,
      1988). Within the self-reference condition narcissism was related to higher
      selection in the trait description task and to higher recall of positive-agentic
      (e.g., clever) traits. This general pattern of results occurred for narcissism
      even while controlling for the related personality variables of self-esteem,
      agency, and communion. In contrast to narcissism, within the self-referent group
      self-esteem predicted higher recall for positive-communal traits (e.g., kind) but
      lower recall for negative-communal traits, a finding consistent with mnemic
      neglect. Overall, results supported the agency model of narcissism and extended
      this model to suggest that narcissists rate themselves more highly not only on
      positive-agentic traits but also on negative-communal traits. 

PMID- 23547687
TI  - Method for electric parametric characterization and optimization of
      electroporation on a chip.
AB  - We have developed a rapid method to optimize the electric parameters of cell
      electroporation. In our design, a pair of ring-dot formatted electrodes was used
      to generate a radial distribution of electric field from the center to the
      periphery. Varied electric field intensity was acquired in different annulus when
      an electric pulse was applied. Cells were cultured on the microchips for adherent
      cell electroporation and in situ observation. The electroporation parameters of
      electric field intensity were explored and evaluated in terms of cell viability
      and transfection efficiency. The optimization was performed in consideration of
      both cell viability, which was investigated to decrease as electric field
      increases, and the transfection rate, which normally increases at stronger
      electric field. The electroporation characteristics HEK-293A and Hela cells were
      investigated, and the optimum parameters were obtained. Verified by a commercial
      electroporation system as well as self-made microchips endowed the optimization
      with wider meaning. At last, as applications, we acquired the optimal
      electroporation pulse intensity of Neuro-2A cells and a type of primary cell
      (human umbilical vein endothelial cell, HUVEC) by one time electroporation using
      the proposed method. 

PMID- 23547689
TI  - Doctors' lifestyles vital for SA's health - global expert.

PMID- 23547688
TI  - NIMART rollout to primary healthcare facilities increases access to
      antiretrovirals in Johannesburg: an interrupted time series analysis.
AB  - INTRODUCTION: South Africa has made remarkable progress in rolling out
      antiretroviral therapy (ART), with the largest number of people (more than 1.4
      million) enrolled on antiretroviral in the world. Decentralisation of services to
      primary health centres (PHCs) has strengthened retention of patients on ART and
      reduced the burden of managing uncomplicated cases at referral hospitals.
      METHODS: This was a ten-step Nurse Initiation Management of Antiretroviral
      Treatment (NIMART) rollout intervention in which nurses from 17 primary
      healthcare facilities of Region F, City of Johannesburg, South Africa, were
      trained and mentored in NIMART by the Wits Reproductive Health and HIV Research
      Institute (WRHI) to commence patients on ART in their PHCs. A total of 20 535
      patients initiated ART during the 30-month study period. Monthly initiations at
      both PHCs and referral clinics were monitored. To test the statistical
      significance of the impact of NIMART rollout on the referral hospital initiations
      and Region F monthly initiations, interrupted time series analysis was applied.
      FINDINGS: Ten-step NIMART was applied, with the first step being establishment of
      NIMART as a priority in order to obtain primary buy-in by the Department of
      Health (DoH) and City of Johannesburg (CoJ). Forty-five professional nurses were
      trained in NIMART by WRHI quality improvement mentors. By the end of September
      2011, all 17 PHCs in Region F were initiating patients on ART. Total initiations
      significantly increased by 99 patients immediately after NIMART rollout (p=0.013)
      and continued to increase by an average of 9 every month (p=0.013), while
      referral facility initiations decreased by 12 (p=0.791) immediately after NIMART
      and then decreased by an average of 18 every month (p=0.01). CONCLUSION: In this
      study, decentralisation of ART initiation by professional nurses was shown to
      increase ART uptake and reduce workload at referral facilities, enabling them to
      concentrate on complicated cases. However, it is important to ensure capacity
      building, training and mentoring of nurses to integrate HIV services in order to
      reduce workload and provide a comprehensive package of care to patients. Engaging
      and having buy-in from DoH/CoJ partners in rolling out NIMART was crucial in
      increasing outputs as well as for sustainability of the NIMART programme.

PMID- 23547690
TI  - E Cape's corruption-busting DG finally ousted.

PMID- 23547691
TI  - Inspanning all the oxen - new Health Foundation.

PMID- 23547692
TI  - Much ado over the new South African PMTCT guidelines.

PMID- 23547694
TI  - Emergency medical treatment and 'do not resuscitate' orders: when can they be
      used?
AB  - The Constitution and the National Health Act provide that nobody shall be refused
      emergency medical treatment. 'Do not resuscitate' (DNR) orders require that
      certain patients should not be given cardiopulmonary resuscitation to save their
      lives. Whether there is a conflict between these two requirements is answered by
      considering: (i) the meaning of emergency medical treatment; (ii) the
      relationship between emergency medical treatment and DNR orders; (iii) the
      meaning of futile medical treatment; (iv) the relationship between DNR orders and
      euthanasia; and (v) when DNR orders may be lawfully used.

PMID- 23547695
TI  - Biobank research: time for discussion and debate.
AB  - The establishment of biobanks is gaining prominence globally. The open and
      evolving nature of biobanks has profound ethical, legal and social implications
      for individual and group autonomy, informed consent, privacy, confidentiality,
      secondary use of samples and data over time, return of results, data sharing,
      benefit sharing with communities, and premature or unplanned closure.
      Complexities also emerge because of increasing international collaborations, and
      differing national positions. Public consultation and involvement are very
      necessary to the success of biobanks. Implementing national laws in an
      internationally consistent manner is problematic.

PMID- 23547696
TI  - Africa's roads: the deadliest in the world.

PMID- 23547697
TI  - Ten years on ART - where to now?

PMID- 23547698
TI  - Thrombosis - prevention is better than cure.

PMID- 23547699
TI  - An integrated approach to improving the availability and utilisation of
      tuberculosis healthcare in rural South Africa.
AB  - BACKGROUND: Patients with tuberculosis (TB) face several challenges in accessing
      care, and an integrated service that includes HIV testing could be preferable for
      them and ensure timely HIV treatment initiation and optimal TB care. OBJECTIVES:
      To investigate factors, including uptake of the offer of HIV testing, associated
      with availability and utilisation of healthcare by TB patients in a rural
      programme devolved to primary care in Hlabisa sub-district, KwaZulu-Natal.
      METHODS: Three hundred TB patients were randomly selected in a two-stage-sampling
      scheme with five primary healthcare clinic (PHC) sampling units selected with
      probability proportional to size. Data were collected using a structured
      questionnaire. We describe key availability and utilisation factors and analyse
      factors associated with being offered an HIV test in multiple regressions
      controlling for sex, age, education, employment and marital status. RESULTS: Most
      patients (75.2%) received care for a first episode of TB, mainly pulmonary.
      Nearly all (94.3%) were offered an HIV test during their current TB treatment
      episode, patients using their closest clinic being substantially more likely to
      have been offered HIV testing than those not using their closest clinic (adjusted
      odds ratio 12.79, p=0.05). About one-fifth (20.3%) of patients did not take
      medication under observation, and 3.4% reported missing taking their tablets at
      some stage. Average travelling time to the clinic and back was 2 hours, most
      patients (56.8%) using minibus taxis. CONCLUSION: We demonstrate high HIV testing
      rates among TB patients in a rural public programme, suggesting appropriate
      management of HIV-TB co-infected patients. We describe healthcare availability
      and utilisation factors that can inform the proposed district management teams
      for PHC re-engineering on areas needing improvement.

PMID- 23547700
TI  - Economic appraisal of dabigatran as first-line therapy for stroke prevention in
      atrial fibrillation.
AB  - BACKGROUND: Dabigatran is an oral anticoagulant direct thrombin inhibitor
      recently registered in South Africa (SA) to reduce the risk of stroke and
      systemic embolism in patients with atrial fibrillation (AF). Owing to the price
      disparity between warfarin (the current gold standard for treatment of patients
      with AF) and dabigatran, we conducted an economic appraisal of the use of
      dabigatran compared with warfarin from a payer perspective in the South African
      private healthcare setting. OBJECTIVES: To estimate the cost-effectiveness (CE)
      and budget impact of dabigatran compared with warfarin for the prevention of
      stroke in AF patients. Methods. A previously published Markov model was populated
      with SA cost and mortality data to estimate the CE and budget impact analysis of
      dabigatran over a lifetime horizon. The model population consisted of a cohort of
      patients of whom those aged younger than 80 years used dabigatran 150 mg twice
      daily and those older than 80 years 110 mg twice daily. Modelled outcomes
      included total cost, quality-adjusted life years (QALYs) and incremental CE ratio
      (ICER), with the effectiveness measured by QALYs gained. RESULTS: Dabigatran
      compared with warfarin as first-line treatment was estimated to have an ICER of
      R93 290 and an average incremental cost per beneficiary per month of R0.39 over a
      5-year period. Conservative assumptions were made regarding the number of
      international normalised ratio monitoring tests for patients on warfarin, and the
      ICER is estimated to decrease by as much as 15.7% under less stringent
      assumptions. A robust sensitivity analysis was also performed. CONCLUSION:
      Dabigatran as first-line treatment compared with warfarin for the use of stroke
      prevention in patients with AF is deemed cost-effective when used in accordance
      with its registered indication in the SA private sector.

PMID- 23547701
TI  - Characteristics, sexual behaviour and risk factors of female, male and
      transgender sex workers in South Africa.
AB  - BACKGROUND: In South Africa, information on sex workers' characteristics, sexual
      behaviour and health needs is limited. Current social, legal and institutional
      factors impede a safe working environment for sex workers and their clients.
      OBJECTIVES: To describe characteristics and sexual behaviour of female, male and
      transgender sex workers, and assess their risk factors for unprotected sex.
      METHODS: Repeat cross-sectional surveys among sex workers were conducted in
      Hillbrow, Sandton, Rustenburg and Cape Town in 2010. Sex workers were interviewed
      once; any re-interviews were excluded from analysis. Unprotected sex was defined
      as any unprotected penetrative vaginal or anal sex with last two clients.
      RESULTS: Trained sex workers interviewed 1 799 sex workers. Sex work was a full
      time profession for most participants. About 8% (126/1 594) of women, 33% (22/75)
      of men, and 25% (12/50) of transgender people had unprotected sex. A quarter of
      anal sex was unprotected. Unprotected sex was 2.1 times (adjusted odds ratio
      (AOR), 95% CI 1.2 - 3.7; p=0.011) more likely in participants reporting daily or
      weekly binge drinking than non-binge drinkers. Male sex workers were 2.9 times
      (AOR, 95%CI 1.6 - 5.3; p<0.001) more likely, and transgender people 2.4 times
      (AOR, 95% CI 1.1 - 4.9; p=0.021) more likely, than females to have unprotected
      sex. Sex workers in Hillbrow, where the only sex work-specific clinic was
      operational, were less likely to have unprotected sex than those in other sites.
      CONCLUSION: Tailored sex work interventions should explicitly include male and
      transgender sex workers, sex work-specific clinics, focus on the risks of
      unprotected anal sex, and include interventions to reduce alcohol harm.

PMID- 23547702
TI  - Evaluation and correlation of mammographically suspicious lesions with
      histopathology at Addington Hospital, Durban.
AB  - BACKGROUND: Stereotactic core-needle biopsies (SCNBs) are a reliable alternative
      to surgical biopsy for microcalcifications. The positive predictive value (PPV)
      of SCNB has been shown to be reproducible in several studies using the Breast
      Imaging Reporting and Data System (BIRADS) classification, which is the current
      gold standard in mammographic reporting. At this stage, no study has been done in
      KwaZulu-Natal to assess local outcomes against BIRADS. The current standard of
      care utilises vacuum-assisted breast biopsy, but is not available in a resource
      constrained environment such as ours. The need, therefore, is for constant
      evaluation of existing practice to ensure that it is optimised for the challenges
      and limitations facing local radiologists. OBJECTIVE: To assess the PPV of SCNB
      in Addington Hospital, and to compare it with that of BIRADS. Material and
      methods. Mammographically detected lesions were assigned to 3 categories: benign,
      indeterminate and suspicious. A retrospective review of 67 SCNBs was performed
      for lesions falling within the suspicious category, and the PPV and rates of
      ductal carcinoma in situ (DCIS) were determined. RESULTS: Our study demonstrated
      a PPV of 20.9%. This correlated well with international studies for BIRADS 4 and
      5 lesions. DCIS accounted for 21.4% of detected malignancies, which is in keeping
      with current literature. CONCLUSION: Despite resource limitations, local outcomes
      were comparable to those of BIRADS. Given our fairly general categorisation of
      lesions, however, it should be emphasised that BIRADS allows better organisation,
      consistency and clarity in breast imaging reporting, as well as accurate data
      comparison between centres facing limitations similar to our own.

PMID- 23547703
TI  - Gastric adenocarcinoma in Zambia: a case-control study of HIV, lifestyle risk
      factors, and biomarkers of pathogenesis.
AB  - BACKGROUND: Gastric cancer is a leading cause of cancer deaths worldwide but
      there are few data from Africa. We recently observed a trend towards diagnosis in
      younger patients. OBJECTIVE: To test the hypothesis that HIV might have altered
      risk factors for acquisition of gastric cancer, in a case-control study in the
      University Teaching Hospital, Lusaka, Zambia. METHODS: Patients (n=52) with
      confirmed gastric adenocarcinoma and controls (n=94) undergoing endoscopy but
      with no macroscopic gastric pathology. Established risk factors and HIV status
      were compared. RESULTS: HIV status did not differ significantly between cases and
      controls (odds ratio 1.03; 95% CI 0.2 - 4.3; p=1.00) and seroprevalence in cases
      was similar to that of the Zambian population. Smoking, regular alcohol intake,
      and gastric atrophy were all associated with cancer in univariate and
      multivariate analysis. Helicobacter pylori serology was positive in 84% of
      patients studied and cagA serology in 66%; neither serological marker was
      associated with cancer. Atrophy was common in cases (57%) and controls (30%) and
      associated with both smoking and alcohol use. Intestinal metaplasia was present
      in 17% of the controls, but was not associated with atrophy. CONCLUSIONS: HIV was
      not associated with gastric cancer and does not explain the apparent younger age
      distribution. Atrophy was common and was not essential for the development of
      intestinal metaplasia, suggesting that gastric carcinogenesis in Africa does not
      always follow the pathway from atrophy to intestinal metaplasia to gastric
      carcinoma (the so-called Correa pathway).

PMID- 23547704
TI  - Venous thromboembolism: prophylactic and therapeutic practice guideline.
AB  - BACKGROUND: Pharmacological prophylactic anticoagulation in many countries,
      including South Africa, is under-prescribed. This has resulted in unacceptable
      rates of morbidity and mortality. METHOD: The Southern African Society of
      Thrombosis and Haemostasis held a meeting to update the previous guideline and
      review new literature including guidelines from other societies. The following
      specialties were represented on the committees: anaesthetics, cardiology,
      clinical haematology, critical care, obstetrics and gynaecology,
      haematopathology, internal medicine, neurology, orthopaedic surgery and
      pulmonology. A draft document was presented at the meeting, which was then
      revised by consensus agreement. To avoid local bias, the guideline was
      adjudicated by recognised international external experts. RESULTS AND CONCLUSION:
      A concise, practical updated guideline for thromboprophylaxis and treatment in
      medical and surgical patients has been produced for South African conditions. It
      is hoped that this guideline will continue to improve anticoagulation practice in
      this country, which we believe will directly benefit patient outcomes.

PMID- 23547705
TI  - Nanostructured potential of optical trapping using a plasmonic nanoblock pair.
AB  - We performed two-dimensional mapping of optical trapping potentials experienced
      by a 100 nm dielectric particle above a plasmon-resonant gold nanoblock pair with
      a gap of several nanometers. Our results demonstrate that the potentials have
      nanoscale spatial structures that reflect the near-field landscape of the
      nanoblock pair. When an incident polarization parallel to the pair axis is
      rotated by 90 degrees , a single potential well turns into multiple potential
      wells separated by a distance smaller than the diffraction limit; this is
      associated with super-resolution optical trapping. In addition, we show that the
      trap stiffness can be enhanced by approximately 3 orders of magnitude compared to
      that with conventional far-field trapping.

PMID- 23547707
TI  - Intermediate-range structure of self-assembled cobalt-based oxygen-evolving
      catalyst.
AB  - Continual improvements in solar-to-fuels catalysis require a genuine
      understanding of catalyst structure-function relationships, not only with respect
      to local order, but also intermediate-range structure. We report the X-ray pair
      distribution function analysis of the nanoscale order of an oxidic cobalt-based
      water-splitting catalyst and uncover an electrolyte dependence in the
      intermediate-range structure of catalyst films. Whereas catalyst films formed in
      borate electrolyte (CoB(i)) exhibit coherent domains consisting of 3-4 nm
      cobaltate clusters with up to three layers, films deposited in phosphate
      electrolyte (CoP(i)) comprise significantly smaller clusters that are not
      coherently stacked. These structural insights are correlated with marked
      differences in activity between CoP(i) and CoB(i) films.

PMID- 23547706
TI  - Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors.
AB  - Screening of the 50000 ChemBridge compound library led to the identification of
      the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT
      L) activity (IC50 = 0.60 MUM) with little effects on the other two major
      proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide
      hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and
      rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI
      1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the
      amide moiety and the two phenyl rings are sensitive toward modifications.
      Hydrophobic residues, such as propyl or butyl in the para position (not ortho or
      meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve
      activity. Compound 11ad (IC50 = 0.37 MUM) is more potent than 1 (IC50 = 3.5 MUM)
      at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and
      inhibiting their survival. The activity of 11ad warrants further preclinical
      investigation of this class as noncovalent proteasome inhibitors.

PMID- 23547709
TI  - The Wnt signalling pathway is upregulated in an in vitro model of acquired
      tamoxifen resistant breast cancer.
AB  - BACKGROUND: Acquired resistance to Tamoxifen remains a critical problem in breast
      cancer patient treatment, yet the underlying causes of resistance have not been
      fully elucidated. Abberations in the Wnt signalling pathway have been linked to
      many human cancers, including breast cancer, and appear to be associated with
      more metastatic and aggressive types of cancer. Here, our aim was to investigate
      if this key pathway was involved in acquired Tamoxifen resistance, and could be
      targeted therapeutically. METHODS: An in vitro model of acquired Tamoxifen
      resistance (named TamR) was generated by growing the estrogen receptor alpha (ER)
      positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen
      (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to
      mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt
      inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt
      reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were
      determined by MTT proliferation assays. RESULTS: TamR cells exhibited increased
      Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes
      associated with both the beta-catenin dependent (AXIN2, MYC, CSNK1A1) and
      independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt
      signalling pathway were upregulated in the TamR cells compared to the parental
      MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a
      (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti
      proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased
      expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may
      contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor,
      IWP-2 inhibited cell proliferation and markers of EMT. CONCLUSIONS: These data
      support the role of the Wnt signalling pathway in acquired resistance to
      Tamoxifen. Further research into the mechanism by which activated Wnt signalling
      inhibits the effects of Tamoxifen should be undertaken. As a number of small
      molecules targeting the Wnt pathway are currently in pre-clinical development,
      combinatorial treatment with endocrine agents and Wnt pathway inhibitors may be a
      useful therapeutic option in the future for a subset of breast cancer patients.

PMID- 23547711
TI  - Rectification behavior of PATP self-assembled on ZnO microrod arrays.
AB  - A rectifying hybrid junction was fabricated by the self-assembly of 4
      aminothiophenol (PATP) on well-aligned ZnO microrod arrays. Good rectification
      behavior was obtained from the device of Al/ZnO/PATP/Al. The electron transport
      at the ZnO/PATP interface was investigated systematically by experimental
      observation and theoretical simulation. X-ray photoelectron spectroscopy (XPS)
      analysis confirmed the strong binding between PATP and ZnO via S-Zn bonds. The
      effective energy barrier and ideality factor of the rectifying diode were
      estimated by the current-voltage (I-V) measurement and thermionic emission
      theory. The molecule dipole effect on work function was studied through energy
      band theory. Theoretical calculation results based on density functional theory
      (DFT) also indicated a significant dipole, caused by the anchoring effect of
      PATP, resulting in the changes of surface electronic characteristics of ZnO.

PMID- 23547710
TI  - Heteromorphic variants of chromosome 9.
AB  - BACKGROUND: Heterochromatic variants of pericentromere of chromosome 9 are
      reported and discussed since decades concerning their detailed structure and
      clinical meaning. However, detailed studies are scarce. Thus, here we provide the
      largest ever done molecular cytogenetic research based on >300 chromosome 9
      heteromorphism carriers. RESULTS: In this study, 334 carriers of heterochromatic
      variants of chromosome 9 were included, being 192 patients from Western Europe
      and the remainder from Easter-European origin. A 3-color-fluorescence in situ
      hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix)
      and 8 different locus-specific probes were applied for their characterization.
      The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9
      heteromorphic patterns. In this study, 17 different variants were detected
      including five yet unreported; the most frequent were pericentric inversions
      (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%),
      and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity,
      a new short nomenclature for the yet reported 24 heteromorphic patterns of
      chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants
      could be narrowed down using locus-specific probes. CONCLUSIONS: Based on this
      largest study ever done in carriers of chromosome 9 heteromorphisms, three of the
      24 detailed variants were more frequently observed in Western than in Eastern
      Europe. Besides, there is no clear evidence that infertility is linked to any of
      the 24 chromosome 9 heteromorphic variants.

PMID- 23547708
TI  - Instruments for assessing the risk of falls in acute hospitalized patients: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Falls are a serious problem for hospitalized patients, reducing the
      duration and quality of life. It is estimated that over 84% of all adverse events
      in hospitalized patients are related to falls. Some fall risk assessment tools
      have been developed and tested in environments other than those for which they
      were developed with serious validity discrepancies. The aim of this review is to
      determine the accuracy of instruments for detecting fall risk and predicting
      falls in acute hospitalized patients. METHODS: Systematic review and meta
      analysis. Main databases, related websites and grey literature were searched. Two
      blinded reviewers evaluated title and abstracts of the selected articles and, if
      they met inclusion criteria, methodological quality was assessed in a new blinded
      process. Meta-analyses of diagnostic ORs (DOR) and likelihood (LH) coefficients
      were performed with the random effects method. Forest plots were calculated for
      sensitivity and specificity, DOR and LH. Additionally, summary ROC (SROC) curves
      were calculated for every analysis. RESULTS: Fourteen studies were selected for
      the review. The meta-analysis was performed with the Morse (MFS), STRATIFY and
      Hendrich II Fall Risk Model scales. The STRATIFY tool provided greater diagnostic
      validity, with a DOR value of 7.64 (4.86 - 12.00). A meta-regression was
      performed to assess the effect of average patient age over 65 years and the
      performance or otherwise of risk reassessments during the patient's stay. The
      reassessment showed a significant reduction in the DOR on the MFS (rDOR 0.75, 95%
      CI: 0.64 - 0.89, p = 0.017). CONCLUSIONS: The STRATIFY scale was found to be the
      best tool for assessing the risk of falls by hospitalized acutely-ill adults.
      However, the behaviour of these instruments varies considerably depending on the
      population and the environment, and so their operation should be tested prior to
      implementation. Further studies are needed to investigate the effect of the
      reassessment of these instruments with respect to hospitalized adult patients,
      and to consider the real compliance by healthcare personnel with procedures
      related to patient safety, and in particular concerning the prevention of falls.

PMID- 23547712
TI  - Characterization of a new high copy Stowaway family MITE, BRAMI-1 in Brassica
      genome.
AB  - BACKGROUND: Miniature inverted-repeat transposable elements (MITEs) are expected
      to play important roles in evolution of genes and genome in plants, especially in
      the highly duplicated plant genomes. Various MITE families and their roles in
      plants have been characterized. However, there have been fewer studies of MITE
      families and their potential roles in evolution of the recently triplicated
      Brassica genome. RESULTS: We identified a new MITE family, BRAMI-1, belonging to
      the Stowaway super-family in the Brassica genome. In silico mapping revealed that
      697 members are dispersed throughout the euchromatic regions of the B. rapa
      pseudo-chromosomes. Among them, 548 members (78.6%) are located in gene-rich
      regions, less than 3 kb from genes. In addition, we identified 516 and 15 members
      in the 470 Mb and 15 Mb genomic shotgun sequences currently available for B.
      oleracea and B. napus, respectively. The resulting estimated copy numbers for the
      entire genomes were 1440, 1464 and 2490 in B. rapa, B. oleracea and B. napus,
      respectively. Concurrently, only 70 members of the related Arabidopsis ATTIRTA-1
      MITE family were identified in the Arabidopsis genome. Phylogenetic analysis
      revealed that BRAMI-1 elements proliferated in the Brassica genus after
      divergence from the Arabidopsis lineage. MITE insertion polymorphism (MIP) was
      inspected for 50 BRAMI-1 members, revealing high levels of insertion polymorphism
      between and within species of Brassica that clarify BRAMI-1 activation periods up
      to the present. Comparative analysis of the 71 genes harbouring the BRAMI-1
      elements with their non-insertion paralogs (NIPs) showed that the BRAMI-1
      insertions mainly reside in non-coding sequences and that the expression levels
      of genes with the elements differ from those of their NIPs. CONCLUSION: A
      Stowaway family MITE, named as BRAMI-1, was gradually amplified and remained
      present in over than 1400 copies in each of three Brassica species. Overall, 78%
      of the members were identified in gene-rich regions, and it is assumed that they
      may contribute to the evolution of duplicated genes in the highly duplicated
      Brassica genome. The resulting MIPs can serve as a good source of DNA markers for
      Brassica crops because the insertions are highly dispersed in the gene-rich
      euchromatin region and are polymorphic between or within species.

PMID- 23547713
TI  - Anterior cingulate cortex and insula response during indirect and direct
      processing of emotional faces in generalized social anxiety disorder.
AB  - BACKGROUND: Generalized social anxiety disorder (gSAD) is associated with a
      heightened neural sensitivity to signals that convey threat, as evidenced by
      exaggerated amygdala and/or insula activation when processing face stimuli that
      express negative emotions. Less clear in the brain pathophysiology of gSAD are
      cortical top down control mechanisms that moderate reactivity in these
      subcortical emotion processing regions. This study evaluated amygdala, insula,
      and anterior cingulate cortex (ACC) activity in gSAD with a novel "Emotional
      Faces Shifting Attention Task" (EFSAT), an adaptation of perceptual assessment
      tasks well-known to elicit amygdala response. In healthy volunteers, the task has
      been shown to engage the amygdala when attention is directed to emotional faces
      and the ACC when attention is directed to shapes, away from emotional faces.
      METHODS: During functional MRI, 29 participants with gSAD and 27 healthy controls
      viewed images comprising a trio of faces (angry, fear, or happy) alongside a trio
      of geometric shapes (circles, rectangles, or triangles) within the same field of
      view. Participants were instructed to match faces or match shapes, effectively
      directing attention towards or away from emotional information, respectively.
      RESULTS: Participants with gSAD exhibited greater insula, but not amygdala,
      activation compared to controls when attending to emotional faces. In contrast,
      when attention was directed away from faces, controls exhibited ACC recruitment,
      which was not evident in gSAD. Across participants, greater ACC activation was
      associated with less insula activation. CONCLUSIONS: Evidence that individuals
      with gSAD exhibited exaggerated insula reactivity when attending to emotional
      faces in EFSAT is consistent with other studies suggesting that the neural basis
      of gSAD may involve insula hyper-reactivity. Furthermore, greater ACC response in
      controls than gSAD when sustained goal-directed attention is required to shift
      attention away from social signals, together with a negative relationship between
      ACC and bilateral insula activity, indicate the ACC may have served a regulatory
      role when the focus of attention was directed to shapes amidst emotional faces.

PMID- 23547714
TI  - Evidence for the requirement of 14-3-3eta (YWHAH) in meiotic spindle assembly
      during mouse oocyte maturation.
AB  - BACKGROUND: The 14-3-3 (YWHA) proteins are central mediators in various cellular
      signaling pathways regulating development and growth, including cell cycle
      regulation. We previously reported that all seven mammalian 14-3-3 isoforms are
      expressed in mouse oocytes and eggs and that, 14-3-3eta (YWHAH) accumulates and
      co-localizes in the region of meiotic spindle in mouse eggs matured in vivo.
      Therefore, we investigated the role of 14-3-3eta in spindle formation during
      mouse oocyte maturation. RESULTS: Examination of oocytes matured in vitro
      demonstrated that 14-3-3eta accumulates in both meiosis I and II spindles. To
      explore if 14-3-3eta interacts directly with alpha-tubulin in meiotic spindles,
      we performed an in situ proximity ligation assay that can detect intracellular
      protein-protein interactions at the single molecule level and which allows
      visualization of the actual interaction sites. This assay revealed a marked
      interaction between 14-3-3eta and alpha-tubulin at the metaphase II spindle. To
      demonstrate a functional role for 14-3-3eta in oocyte maturation, mouse oocytes
      were microinjected with a translation-blocking morpholino oligonucleotide against
      14-3-3eta mRNA to reduce 14-3-3eta protein synthesis during oocyte maturation.
      Meiotic spindles in those cells were examined by immunofluorescence staining of
      14-3-3eta and alpha-tubulin along with observation of DNA. In 76% of cells
      injected with the morpholino, meiotic spindles were found to be deformed or
      absent and there was reduced or no accumulation of 14-3-3eta in the spindle
      region. Those cells contained clumped chromosomes, with no polar body formation.
      Immunofluorescence staining of 14-3-3eta and alpha-tubulin in control eggs
      matured in vitro from uninjected oocytes and oocytes microinjected with the
      ineffective, inverted form of a morpholino against 14-3-3eta, a morpholino
      against 14-3-3gamma, or deionized water showed normal, bipolar spindles.
      CONCLUSIONS: The results indicate that 14-3-3eta is essential for normal meiotic
      spindle formation during in vitro maturation of mouse oocytes, in part by
      interacting with alpha-tubulin, to regulate the assembly of microtubules. These
      data add to our understanding of the roles of 14-3-3 proteins in mouse oocyte
      maturation and mammalian reproduction.

PMID- 23547715
TI  - Patterns of radiotherapy practice for biliary tract cancer in Japan: results of
      the Japanese radiation oncology study group (JROSG) survey.
AB  - BACKGROUND: The patterns of radiotherapy (RT) practice for biliary tract cancer
      (BTC) in Japan are not clearly established. METHODS: A questionnaire-based
      national survey of RT used for BTC treatment between 2000 and 2011 was conducted
      by the Japanese Radiation Oncology Study Group. Detailed information was
      collected for 555 patients from 31 radiation oncology institutions. RESULTS: The
      median age of the patients was 69 years old (range, 33-90) and 81% had a good
      performance status (0-1). Regarding RT treatment, 78% of the patients were
      treated with external beam RT (EBRT) alone, 17% received intraluminal
      brachytherapy, and 5% were treated with intraoperative RT. There was no
      significant difference in the choice of treatment modality among the BTC
      subsites. Many patients with EBRT were treated with a total dose of 50 or 50.4 Gy
      (~40%) and only 13% received a total dose >=60 Gy, even though most institutions
      (90%) were using CT-based treatment planning. The treatment field consisted of
      the primary tumor (bed) only in 75% of the patients. Chemotherapy was used for
      260 patients (47%) and was most often administered during RT (64%, 167/260),
      followed by after RT (63%, 163/260). Gemcitabine was the most frequently used
      drug for chemotherapy. CONCLUSIONS: This study established the general patterns
      of RT practice for BTC in Japan. Further surveys and comparisons with results
      from other countries are needed for development and optimization of RT for
      patients with BTC in Japan.

PMID- 23547716
TI  - Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells
      using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals.
AB  - Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the
      diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA,
      is closely related to the growth of cancer including proliferation, metastasis,
      invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a
      few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific
      magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical
      properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs
      were efficiently phase-transferred using aminated polysorbate 80 (P80)
      synthesized by introducing spermine molecules on the hydroxyl groups of P80.
      Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different
      ratios of HA on the equal amount of phase-transferred MNCs. The optimized
      conjugation ratio of HA against magnetic content was identified to exhibit not
      only effective CD44 finding ability but also high cell viability through in vitro
      experiments. The results of this study demonstrate that the suggested HA-MRCA
      shows strong potential to be used for accurate tumor diagnosis.

PMID- 23547720
TI  - Missed lipoma of the spermatic cord.
AB  - The aim of the research was to determine the incidence, significance, and anatomy
      of spermatic cord and round ligament lipomas. Between 2000 and 2010 we evaluated
      969 consecutive patients with 1,070 indirect inguinal hernias, who underwent open
      repair. A total of 22 lipomas of the spermatic cord or round ligament were
      identified and resected in 22 patients. No neoplastic changes confirmed in
      histopathologic examinations of the specimens were reported. Lipomas of the cord
      and round ligament occur with a considerable incidence. We believe that even if
      there is no peritoneal sac, the herniation of extraperitoneal fat through the
      inguinal canal should be counted as an inguinal hernia, and it requires adequate
      treatment.

PMID- 23547718
TI  - Systematic antibody generation and validation via tissue microarray technology
      leading to identification of a novel protein prognostic panel in breast cancer.
AB  - BACKGROUND: Although omic-based discovery approaches can provide powerful tools
      for biomarker identification, several reservations have been raised regarding the
      clinical applicability of gene expression studies, such as their prohibitive
      cost. However, the limited availability of antibodies is a key barrier to the
      development of a lower cost alternative, namely a discrete collection of
      immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a
      systematic approach to generate and screen affinity-purified, mono-specific
      antibodies targeting progression-related biomarkers, with a view towards
      developing a clinically applicable IHC-based prognostic biomarker panel for
      breast cancer. METHODS: We examined both in-house and publicly available breast
      cancer DNA microarray datasets relating to invasion and metastasis, thus
      identifying a cohort of candidate progression-associated biomarkers. Of these, 18
      antibodies were released for extended analysis. Validated antibodies were
      screened against a tissue microarray (TMA) constructed from a cohort of
      consecutive breast cancer cases (n = 512) to test the immunohistochemical
      surrogate signature. RESULTS: Antibody screening revealed 3 candidate prognostic
      markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein
      kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain
      Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with
      poor prognosis, whilst increased expression of PDZK1 was associated with good
      prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1
      expression was associated with decreased recurrence-free survival (p < 0.001) and
      breast cancer-specific survival (BCSS) (p < 0.001). This novel signature was
      associated with high tumour grade (p < 0.001), positive nodal status (p = 0.029),
      ER-negativity (p = 0.006), Her2-positivity (p = 0.036) and high Ki67 status (p <
      0.001). However, multivariate Cox regression demonstrated that the signature was
      not a significant predictor of BCSS (HR = 6.38; 95% CI = 0.79-51.26, p = 0.082).
      CONCLUSIONS: We have developed a comprehensive biomarker pathway that extends
      from discovery through to validation on a TMA platform. This proof-of-concept
      study has resulted in the identification of a novel 3-protein prognostic panel.
      Additional biochemical markers, interrogated using this high-throughput platform,
      may further augment the prognostic accuracy of this panel to a point that may
      allow implementation into routine clinical practice.

PMID- 23547721
TI  - Postinfarction ventricular septal rupture - a rare complication remains challenge
      for cardiac surgical team.
AB  - The incidence of post infarction ventricular septal rupture (PIVSR) is decreasing
      in the last years due to aggressive treatment of myocardial infarction with early
      percutaneous coronary interventions. As a consequence patients with PIVSR are
      referred to surgery more often with significant heart failure. The aim of this
      retrospective study was to assess the influence of these on the operative results
      and to identify the risk factors of operative mortality. A retrospective analysis
      of prospectively collected data of patients with the PIVSR admitted to our center
      from November 2004 to February 2012 was performed. Variables were analyzed using
      two-dimensional correspondence analysis. There were 25 patients (12 males and 13
      females) with mean age 70.2 years (47-82) operated on; 17 (68%) presented with
      anterior and 8 (32%) with posterior PIVSR. Eighteen patients (72%) had acute
      heart failure, 13 (52%) presented with cardiogenic shock. Before surgery,
      intraaortic balloon pump (IABP) had 20 (80%) patients; in 4 (16%) a ventricular
      assist device was used, either Extracorporeal Membrane Oxygenation (ECMO) or
      centrifugal pumps as biventricular assist. Operative mortality was 40% (10 pts.).
      Four patients (12%) had small non-significant recurrent shunt on postoperative
      echocardiography. Although majority of patients with PIVSR have significant heart
      failure prior to surgery the operative mortality remains comparable to older
      studies. Predictors of perioperative death were concomitant surgical
      reconstruction of the left ventricle, renal impairment before operation, male
      gender, history of coronary artery disease, PIVSR location posterior, and shock
      at surgery.

PMID- 23547722
TI  - Colorectal cancer in younger patients - a single centre analysis.
AB  - Debate surrounds the nature of colorectal cancers in younger patients and whether
      they are more likely to present with aggressive disease. Pearson's correlation
      coefficient was used to examine whether a relationship exists between age and
      variables such as family history, mucinous tumours, metastases and final
      pathology. 41 patients under the age of 45 were diagnosed and operated for
      colorectal cancer between September 1998 and December 2010 in our centre.
      Nineteen patients were under the mean age of 35 years. There was no correlation
      between younger patients and metastatic disease (r= -0.129, p=0.440) or family
      history (r= -0.258, p=0.123). There was no correlation between age and Dukes
      staging (r= -0.052, p=0.756), tumour stage (r= -0.110, p=0.516), nodal status (r=
      -0.053, p=0.751), mucinous tumours (r=0.104, p=0.569) and cell differentiation
      (r= 0.046, p=0.787). Overall mortality was 26% and of those who survived 10% have
      metastatic disease. Median survival was 26 months after surgery. Younger patients
      under 45 appear to be a homogenous group in relation to colorectal tumour
      characteristics. Further longitudinal studies to examine the differences between
      this group and older people are needed.

PMID- 23547723
TI  - Evaluation of the three-year experience with all-ceramic crowns with
      polycrystalline ceramic cores.
AB  - The objective of the study was to evaluate the clinical outcomes of all-ceramic
      crowns three years after placement of the restoration in the oral cavity. The aim
      of the present clinical study were surveyed the Procera(r), Cercon(r) and LAVATM
      systems. In total, 121 crowns were followed in 33 patients (7 men and 26 women)
      with an average age of 53.5 years. The eighty crowns were placed in anterior and
      forty one crowns in posterior teeth. The crowns were fabricated in two dental
      laboratories and delivered in two private dental practices. The clinical trial
      was conducted according to American Dental Association guidelines. The patients
      were requested to provide their consent to the regular clinical examination
      including radiographic and photographic records. A total of 102 crowns were made
      of zirconium oxide ceramic cores - 58 Cercon(r); 43 LAVATM, while 19 crowns were
      made of aluminum oxide cores Procera(r). The veneering ceramic LAVATM Ceram was
      used. The success rate was analyzed using Kaplan-Meier statistics and, in our
      case, the overall three-year success rate reached 96.7%. All-ceramic crowns with
      polycrystalline ceramic cores have low susceptibility to fracture, in this study
      just 3.3%.

PMID- 23547724
TI  - Isolated extrapontine myelinolysis of osmotic demyelination syndrome.
AB  - The osmotic demyelination syndrome (ODS) has been identified as a complication of
      the rapid correction of hyponatremia for decades (King and Rosner, 2010).
      However, in recent years, a variety of other medical conditions have been
      associated with the development of ODS, independent of changes in serum sodium
      which cause a rapid changes in osmolality of the interstitial (extracellular)
      compartment of the brain leading to dehydration of energy-depleted cells with
      subsequent axonal damage that occurs in characteristic areas (King and Rosner,
      2010). Slow correction of the serum sodium concentration and additional
      administration of corticosteroids seems to be a major prevention step in ODS
      patients. In the current report we aimed to share a rare case which we observed
      in our clinic.

PMID- 23547725
TI  - Metastasis-induced pancreatitis: case report.
AB  - This report aims to highlight the importance of malignancy exclusion in the
      absence of common aetiology in acute pancreatitis. An 83-year-old woman presented
      acutely with pancreatitis. There had been no history suggestive of gallstones
      disease and she rarely consumed alcohol. Subsequent ultrasound scan revealed no
      gallstones but multiple liver metastatic lesions. Further carcinomatosis
      involving the pancreas, right ovary, pelvic lymphatics and nodular disease of the
      lungs was demonstrated on computed tomography. Immuno-histochemistry of liver
      biopsy showed positivity for markers suggestive of metastasis arising from lung
      small cell carcinoma. The case was discussed at the lung multidisciplinary
      meeting and the patient was referred for community palliative care. Early
      diagnosis of metastasis induced pancreatitis allows immediate institution of
      palliative care, if not suitable for aggressive pharmaco-surgical intervention.

PMID- 23547726
TI  - Intestinal ischaemia associated with carcinoid tumor: a case report with review
      of the pathogenesis.
AB  - Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that are often
      indolent and may not become clinically apparent until there is a metastatic
      spread or evidence of carcinoid syndrome. A 44-year-old man presented to our
      clinic department with a history of previous left colon cancer operation, chronic
      crampy left lower quadrant pain, mass and severe anemia. A MR scan was obtained
      which demonstrated a calcified mesenteric mass 12*8*10 cm diameter with
      surrounding left colon mesenteric infiltration. The liver was normal. A case of
      ischaemic ileal necrosis is reported. It was associated with elastic vascular
      sclerosis produced by mesenteric metastases of an ileal carcinoid tumor. It is
      postulated that intestinal ischaemia may be of more importance in the production
      of abdominal pain by carcinoid tumors than has been generally accepted, and that
      it is the result of functional and structural changes in and around the
      mesenteric blood vessels, caused by substances secreted by the carcinoid tumor.

PMID- 23547727
TI  - Intussusception secondary to a meckel diverticulum in an adolescent.
AB  - Adult intussusception caused by an inverted Meckel diverticulum is rare. We
      report a 39-year-old Turkish man with intussusception due to Meckel
      diverticulitis. Ileoileal intussusception was suggested by computed tomography.
      Exploration revealed ileoileal intussusception with Meckel diverticulum. A
      diverticulectomy with small bowel resection was performed.

PMID- 23547728
TI  - Discovery of 4-Aryl-2-benzoyl-imidazoles as tubulin polymerization inhibitor with
      potent antiproliferative properties.
AB  - A series of 4-aryl-2-benzoyl-imidazoles were designed and synthesized based on
      our previously reported 2-aryl-4-benzoyl-imidazole (ABI) derivatives. The new
      structures reversed the aryl group and the benzoyl group of previous ABI
      structures and were named as reverse ABI (RABI) analogues. RABIs were evaluated
      for biological activity against eight cancer cell lines including multidrug
      resistant cancer cell lines. In vitro assays indicated that several RABI
      compounds had excellent antiproliferative properties, with IC50 values in the low
      nanomolar range. The average IC50 of the most active compound 12a is 14 nM. In
      addition, the mechanism of action of these new analogues was investigated by cell
      cycle analysis, tubulin polymerization assay, competitive mass spectrometry
      binding assay, and molecular docking studies. These studies confirmed that these
      new RABI analogues maintain their mechanisms of action by disrupting tubulin
      polymerization, similar to their parental ABI analogues.

PMID- 23547729
TI  - Photoinduced and thermal denitrogenation of bulky triazoline crystals: insights
      into solid-to-solid transformation.
AB  - The photoinduced and thermal denitrogenation of crystalline triazolines with
      bulky substituents leads to the quantitative formation of aziridines in clean
      solid-to-solid reactions despite very large structural changes in the transition
      from reactant to product. Analysis of the reaction progress by powder X-ray
      diffraction, solid-state (13)C CPMAS NMR, solid-state FTIR spectroscopy, and
      thermal analysis has revealed that solid-to-solid reactions proceed either
      through metastable phases susceptible to amorphization or by mechanisms that
      involve a reconstructive phase transition that culminates in the formation of the
      stable phase of the product. While the key for a solid-to-solid transformation is
      that the reaction occurs below the eutectic temperature of the reactant and
      product two-component system, experimental evidence suggests that those reactions
      will undergo a reconstructive phase transition when they take place above the
      glass transition temperature.

PMID- 23547730
TI  - Serum pigment epithelium-derived factor levels are independently correlated with
      the presence of coronary artery disease.
AB  - BACKGROUND: Pigment epithelium-derived factor (PEDF) has been proved to be
      closely correlated with metabolic syndrome (MetS) and its components that are all
      risk factors of cardiovascular disease and may play a protective role against
      vascular injury and atherosclerosis. The present study was designed to
      investigate the relationship between serum PEDF and coronary artery disease
      (CAD). METHODS: A total of 312 consecutive in-patients (including 228 with CAD
      and 197 with MetS) who underwent coronary angiography were enrolled. Serum PEDF
      was measured by sandwich enzyme immunoassay and used to carry out multivariate
      stepwise regression analysis to assess correlation with patient demographic and
      clinical parameters. Multiple logistic regression analysis was performed to
      identify factors independently correlated with CAD. RESULTS: Patients with MetS
      had significantly higher levels of serum PEDF than non-MetS subjects (11.1(8.2,
      14.2) vs. 10.1(7.6, 12.4) MUg/mL; P < 0.05). Patients with CAD also had
      significantly higher serum PEDF than non-CAD subjects (11.0(8.1, 14.2) vs.
      10.3(8.1, 12.8) MUg/mL; P < 0.05). Triglyceride (TG), C-reactive protein (CRP),
      estimated glomerular filtration rate (eGFR), and hypoglycemic therapy were
      independently correlated with serum PEDF levels, and serum PEDF was independently
      positively correlated with CAD. CONCLUSIONS: Serum PEDF levels are independently
      positively associated with CAD in a Chinese population. Elevated PEDF may act as
      a protective response against vascular damage and subsequent CAD.

PMID- 23547731
TI  - Effects of iron polymaltose complex, ferrous fumarate and ferrous sulfate
      treatments in anemic pregnant rats, their fetuses and placentas.
AB  - Although oral iron preparations are widely prescribed to prevent and to treat
      iron deficiency anemia in pregnancy, comparative data on their effects to the
      mother, fetus and placenta are limited. In this study, the effects of oral iron
      polymaltose complex (IPC), ferrous fumarate (FF) and ferrous sulfate (FS) were
      compared in anemic pregnant rats, their fetuses and placentas. Hematological
      variables and oxidative stress markers in the liver, heart and kidneys of the
      dams and fetuses as well as the markers for oxidative stress, inflammation and
      hypoxia in placentas were assessed. Pregnancy outcome was measured by number of
      fetuses, and by neonate and placental weight. All therapies were comparably
      effective in correcting anemia. FS and FF, but not IPC, resulted in liver damage
      in dams and oxidative stress in dams, fetuses and placentas. FS group presented
      the highest catalase and GPx levels in dams, fetuses and placentas. IPC, but not
      FF or FS, restored normal TNF-alpha and IL6 expression levels in placentas
      whereas FS-treated animals presented the highest cytokine levels, suggesting a
      local inflammatory reaction. Anemia-induced high levels of HIF-1alpha were
      partially lowered by IPC and FF but further elevated by FS. Most of the negative
      effects associated with IDA were resolved by IPC treatment. Especially FS
      treatment was found to elicit hepatic damage in the dams, oxidative stress in the
      dams, fetuses and placenta as well as inflammation and high levels of HIF-1alpha
      in the placenta. Pregnancy outcome of FFand FS-treated animals was worse than
      that of IPC-treated animals. 

PMID- 23547732
TI  - Myopericarditis, as the first sign of rheumatoid arthritis relapse, evaluated by
      cardiac magnetic resonance.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) affects many organs, including the heart.
      Cardiac magnetic resonance (CMR) can assess heart pathophysiology in RA. AIM: To
      evaluate, using CMR, RA patients under remission with recent onset of cardiac
      symptoms. PATIENTS AND METHODS: Twenty RA under remission (15F/5M), aged 60+/-5
      yrs, with recent onset of cardiac symptoms (RAH), were prospectively evaluated by
      CMR. The CMR included left ventricular ejection fraction (LVEF), T2-weighted (T2
      W), early (EGE) and late gadolinium enhanced (LGE) images evaluation. Their
      results were compared with those of 20 RA under remission without cardiac
      symptoms (RAC) and 18 with systemic lupus erythematosus (SLE) with clinically
      overt myocarditis. RESULTS: Cardiac enzymes were abnormal in 5/20 RAH. CMR
      revealed inferior wall myocardial infarction in 2/20 (1M, 1F) and myocarditis in
      13/20 (8M/5F) RAH. The T2 ratio of myocardium to skeletal muscle was increased in
      RAH and SLE compared to RAC (2.5 +/- 0.05 and 3.4+/-0.7 vs 1.8 +/- 0.5, p<0.001).
      EGE was increased in RAH and SLE compared to RAC (15 +/- 3 and 12+/-4.7 vs 2.7+/
      0.8, p<0.001). Epicardial LGEs were identified in 10/13 and pericarditis in 6/13
      RAH. Coronary angiography, performed in 5 RAH with increased cardiac enzymes,
      proved a right coronary artery obstruction in 2/5. In 3/5 with CMR positive for
      myocarditis, coronary arteries were normal, but endomyocardial biopsy revealed
      inflammation with normal PCR. An RA relapse was observed after 7-40 days in 10/13
      RAH with myopericarditis. The one year follow up showed that a) RAH with
      myocarditis had more disease relapses and b) CHF was developed in 4 RAH with
      myocarditis. CONCLUSIONS: Myopericarditis with atypical presentation, diagnosed
      by CMR in RA under remission, may precede the development of RA relapse. In 1
      year follow up, RA patients with history of myocarditis have a higher frequency
      of disease relapse and may develop CHF.

PMID- 23547733
TI  - A mysterious case of gastroparesis: could the secret be found in a drink?
AB  - BACKGROUND: Gastroparesis is a disorder characterized by delayed gastric emptying
      of a meal in the absence of a mechanical gastric outlet obstruction. Idiopathic
      gastroparesis is at least as common as diabetic gastroparesis in most case
      series, and the true prevalence of gastroparesis is unknown. RESULTS: We report
      here an interesting case of idiopathic gastroparesis characterized by sudden
      onset in a female patient. The diagnosis was confirmed by ultrasonographic study
      of gastric emptying and electrogastrography, by gastric endoscopy/histology, and
      finally by allergy tests. The disorder was found to be due to a rare cause,
      namely an allergic predisposition. In fact, our patient, who demonstrated an
      allergy to gold salts, had drunk a glass of a liqueur containing gold flakes and
      developed an eosinophilic aggregation in the gastric mucosa observed at gastric
      endoscopy/histology. The symptoms disappeared after steroid administration.
      CONCLUSION: Our experience suggests that gastric histology and close enquiry into
      any history of allergy may be useful diagnostic tools in cases of idiopathic
      gastroparesis.

PMID- 23547734
TI  - Seeded growth of monodisperse gold nanorods using bromide-free surfactant
      mixtures.
AB  - We demonstrate for the first time that monodisperse gold nanorods (NRs) with
      broadly tunable dimensions and longitudinal surface plasmon resonances can be
      synthesized using a bromide-free surfactant mixture composed of
      alkyltrimethylammonium chloride and sodium oleate. It is found that uniform gold
      NRs can be obtained even with an iodide concentration approaching 100 MUM in the
      growth solution. In contrast to conventional wisdom, our results provide
      conclusive evidence that neither bromide as the surfactant counterion nor a high
      concentration of bromide ions in the growth solution is essential for gold NR
      formation. Correlated electron microscopy study of three-dimensional structures
      of gold NRs reveals a previously unprecedented octagonal prismatic structure
      enclosed predominantly by high index {310} crystal planes. These findings should
      have profound implications for a comprehensive mechanistic understanding of
      seeded growth of anisotropic metal nanocrystals.

PMID- 23547735
TI  - Plasma-enhanced antibody immobilization for the development of a capillary-based
      carcinoembryonic antigen immunosensor using laser-induced fluorescence
      spectroscopy.
AB  - In this study, antibody immobilization using a microwave-induced H2O/Ar plasma
      pretreatment was achieved for the first time. Plasma was used to activate the
      surface of a capillary-based immunosensor by increasing the density of silicon
      hydroxyls and dangling bonds to ensure better silanization. The capture
      antibodies were covalently immobilized after the silanized surface reacted with
      glutaraldehyde and antibodies. A Cy3-labeled detection antibody was used in
      combination with the antigen captured by the immunosensor to complete the
      sandwich-type immunoassay, and the signals were measured using a laser-induced
      fluorescence system. Microwave-induced H2O/Ar plasma pretreatment of the
      carcinoembryonic antigen (CEA) immunosensor improved the antibody immobilization,
      and there was an obvious improvement in the linear detection range, i.e., 1 order
      of magnitude compared with a commercial enzyme-linked immunosorbent assay
      (ELISA). This novel immobilization method dramatically improved the detection
      limit (0.5 pmol/L CEA) and sensitivity. Assay validation studies indicated that
      the correlation coefficient reached 0.9978, and the relative standard deviations
      were <7% for all samples, with recoveries of 99.7-107.1%. Furthermore, the
      immunosensor was applied successfully to CEA determination in actual saliva
      specimens with high sensitivity, acceptable precision, and reasonable accuracy.
      This enhanced CEA immunosensor based on microwave-induced H2O/Ar plasma was
      demonstrated to be a sensitive tool for CEA diagnostics. 

PMID- 23547736
TI  - Prediction of Drosophila melanogaster gene function using Support Vector
      Machines.
AB  - BACKGROUND: While the genomes of hundreds of organisms have been sequenced and
      good approaches exist for finding protein encoding genes, an important remaining
      challenge is predicting the functions of the large fraction of genes for which
      there is no annotation. Large gene expression datasets from microarray
      experiments already exist and many of these can be used to help assign potential
      functions to these genes. We have applied Support Vector Machines (SVM), a
      sigmoid fitting function and a stratified cross-validation approach to analyze a
      large microarray experiment dataset from Drosophila melanogaster in order to
      predict possible functions for previously un-annotated genes. A total of
      approximately 5043 different genes, or about one-third of the predicted genes in
      the D. melanogaster genome, are represented in the dataset and 1854 (or 37%) of
      these genes are un-annotated. RESULTS: 39 Gene Ontology Biological Process (GO
      BP) categories were found with precision value equal or larger than 0.75, when
      recall was fixed at the 0.4 level. For two of those categories, we have provided
      additional support for assigning given genes to the category by showing that the
      majority of transcripts for the genes belonging in a given category have a
      similar localization pattern during embryogenesis. Additionally, by assessing the
      predictions using a confidence score, we have been able to provide a putative GO
      BP term for 1422 previously un-annotated genes or about 77% of the un-annotated
      genes represented on the microarray and about 19% of all of the un-annotated
      genes in the D. melanogaster genome. CONCLUSIONS: Our study successfully employs
      a number of SVM classifiers, accompanied by detailed calibration and validation
      techniques, to generate a number of predictions for new annotations for D.
      melanogaster genes. The applied probabilistic analysis to SVM output improves the
      interpretability of the prediction results and the objectivity of the validation
      procedure.

PMID- 23547738
TI  - Origin of electrochromism in high-performing nanocomposite nickel oxide.
AB  - Electrochromic effects of transition metal oxides provide a great platform for
      studying lithium intercalation chemistry in solids. Herein, we report on an
      electronically modified nanocomposite nickel oxide (i.e., Li2.34NiZr0.28Ox) that
      exhibits significantly improved electrochromic performance relative to the state
      of-the-art inorganic electrochromic metal oxides in terms of charge/discharge
      kinetics, bleached-state transparency, and optical modulation. The knowledge
      obtained from O K-edge X-ray absorption spectroscopy (XAS) and X-ray
      photoelectron spectroscopy (XPS) suggests that the internally grown lithium
      peroxide (i.e., Li2O2) species plays a major role in facilitating charge transfer
      thus enabling optimal electrochromic performance. This understanding is relevant
      to recent theoretical studies concerning conductivity in Li2O2 for lithium-air
      batteries (as cited in the main text). Furthermore, we elucidate the
      electrochromism in modified nickel oxide in lithium ion electrolyte with the aid
      of Ni K-edge XAS and Ni L-edge XAS studies. The electrochromism in the nickel
      oxide materials arises from the reversible formation of hole states on the NiO6
      units, which then impacts the Ni oxidation state through the Ni3d-O2p
      hybridization states. This study sheds light on the lithium intercalation
      chemistry for general energy storage and semiconductor applications.

PMID- 23547739
TI  - Guest-triggered Zn(II) translocation and supramolecular nuclearity control in
      calix[6]arene-based complexes.
AB  - Two new polytopic ligands based on a calix[6]arene scaffold were synthesized. The
      truncated cone-shaped calixarene was functionalized at its small rim by a tris
      imidazole site, aimed at generating a tetrahedral Zn(II) complex, where a fourth
      labile site inside the cavity is accessible through the funnel provided by its
      large rim. Tridentate aza ligands (either two or three) were then grafted at this
      large rim (the entrance of the cavity). Zn(II) coordination studies, monitored by
      (1)H NMR spectroscopy, showed unprecedented behavior in this family of
      heteropolytopic ligands. Indeed, it gives access to complexes of various
      nuclearities in acetonitrile, where zinc binding is under the supramolecular
      control of the guest. It is first shown that, in the absence of a good guest
      donor (a primary amine), Zn(II) binding is favored at the large rim where two
      tridentate nitrogenous groups can form an octahedral complex. The addition of a
      long guest such as heptylamine induces the quantitative translocation of the
      Zn(II) ion from the large rim octahedral (O(h)) site to the small rim tetrahedral
      (T(d)) site provided by the trisimidazole core and the guest ligand. With 2 equiv
      of Zn(II), well-defined dinuclear complexes were obtained and isolated, with one
      Zn(II) ion bound at each rim. Interestingly, it is shown that the binding mode at
      the large rim is under the supramolecular control of the guest bound at the small
      rim (with short guests, the O(h) environment is obtained at the large rim,
      whereas long guests disrupt this core through an induced-fit process); the
      partially included and dangling alkyl chain opens the large rim (entrance of the
      cavity) and pushes apart the tridentate moieties. As a result, a guest-induced
      switch of Zn(II) binding mode occurs and frees one of the tridentate groups from
      coordination, allowing further extension of the complex nuclearity.

PMID- 23547740
TI  - Reduced contribution of thermally labile sugar lesions to DNA double strand break
      formation after exposure to heavy ions.
AB  - In cells exposed to low linear energy transfer (LET) ionizing-radiation (IR),
      double-strand-breaks (DSBs) form within clustered-damage-sites (CDSs) from
      lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that
      all DSBs form promptly and are immediately detected by the cellular DNA-damage
      response (DDR) apparatus. However, there is evidence that the pool of DSBs
      detected by physical methods, such as pulsed-field gel electrophoresis (PFGE),
      comprises not only promptly forming DSBs (prDSBs) but also DSBs developing during
      lysis at high temperatures from thermally-labile sugar-lesions (TLSLs). We
      recently demonstrated that conversion of TLSLs to DNA breaks and ultimately to
      DSBs also occurs in cells during the first hour of post-irradiation incubation at
      physiological temperatures. Thus, TLSL-dependent DSBs (tlDSBs) are not an
      avoidable technique-related artifact, but a reality the cell always faces. The
      biological consequences of tlDSBs and the dependence of their formation on LET
      require in-depth investigation. Heavy-ions (HI) are a promising high-LET
      radiation modality used in cancer treatment. HI are also encountered in space and
      generate serious radiation protection problems to prolonged space missions. Here,
      we study, therefore, the effect of HI on the yields of tlDSBs and prDSBs. We
      report a reduction in the yield of tlDBSs stronger than that earlier reported for
      neutrons, and with pronounced cell line dependence. We conclude that with
      increasing LET the complexity of CDSs increases resulting in a commensurate
      increase in the yield prDSBs and a decrease in tlDSBs. The consequences of these
      effects to the relative biological effectiveness are discussed.

PMID- 23547741
TI  - The acute and long-term management of food allergy: protocol for a rapid
      systematic review.
AB  - BACKGROUND: Allergic reactions to plant and animal derived food allergens can
      have serious consequences for sufferers and their families. The associated
      social, emotional and financial costs make it a priority to understand the best
      ways of managing such immune-mediated hypersensitivity responses. Conceptually,
      there are two main approaches to managing food allergy: those targeting immediate
      symptoms and those aiming to support long-term management of the condition. The
      European Academy of Allergy and Clinical Immunology is developing guidelines
      about what constitutes an effective treatment for food allergies. As part of the
      guidelines development process, a systematic review is planned to examine
      published research about the management of food allergy in adults and children.
      METHODS: Seven bibliographic databases were searched from their inception to
      September 30, 2012 for systematic reviews, randomized controlled trials, quasi
      randomized controlled trials, controlled clinical trials, controlled before-and
      after studies and interrupted time series. Experts were consulted for additional
      studies. There were no language or geographic restrictions. Studies were
      critically appraised using the Critical Appraisal Skills Program and Cochrane
      EPOC Risk of Bias tools. Only studies where people had a diagnosis of food
      allergy or reported a history of food allergy were included. This means that many
      studies of conditions that may be caused by food allergy are omitted, because
      only research in people with an explicit diagnosis or history was eligible.
      DISCUSSION: Many initiatives have been tested to treat the immediate symptoms of
      food allergy (acute management) and to deal with longer lasting symptoms or
      induce tolerability to potential allergens (long-term management). The best
      management strategies for people with food allergy are likely to depend on the
      type of allergy, symptom manifestations and age. There is a real need to increase
      the amount of high quality research devoted to treatment strategies for food
      allergy. Food allergy can be debilitating and is affecting an increasing number
      of children and adults. With such little known about how to effectively manage
      the condition and its manifestations, this appears a priority for future
      research.

PMID- 23547742
TI  - Hippo pathway genes developed varied exon numbers and coevolved functional
      domains in metazoans for species specific growth control.
AB  - BACKGROUND: The Hippo pathway controls growth by mediating cell proliferation and
      apoptosis. Dysregulation of Hippo signaling causes abnormal proliferation in both
      healthy and cancerous cells. The Hippo pathway receives inputs from multiple
      developmental pathways and interacts with many tissue-specific transcription
      factors, but how genes in the pathway have evolved remains inadequately revealed.
      RESULTS: To explore the origin and evolution of Hippo pathway, we have
      extensively examined 16 Hippo pathway genes, including upstream regulators and
      downstream targets, in 24 organisms covering major metazoan phyla. From simple to
      complex organisms, these genes are varied in the length and number of exons but
      encode conserved domains with similar higher-order organization. The core of the
      pathway is more conserved than its upstream regulators and downstream targets.
      Several components, despite existing in the most basal metazoan sponges, cannot
      be convincingly identified in other species. Potential recombination breakpoints
      were identified in some genes. Coevolutionary analysis reveals that most
      functional domains in Hippo genes have coevolved with interacting functional
      domains in other genes. CONCLUSIONS: The two essential upstream regulators
      cadherins fat and dachsous may have originated in the unicellular organism
      Monosiga brevicollis and evolved more significantly than the core of the pathway.
      Genes having varied numbers of exons in different species, recombination events,
      and the gain and loss of some genes indicate alternative splicing and species
      specific evolution. Coevolution signals explain some species-specific loss of
      functional domains. These results significantly unveil the structure and
      evolution of the Hippo pathway in distant phyla and provide valuable clues for
      further examination of Hippo signaling.

PMID- 23547743
TI  - Diameter-sensitive biocompatibility of anodic TiO2 nanotubes treated with
      supercritical CO2 fluid.
AB  - This work reports on the diameter-sensitive biocompatibility of anodic TiO2
      nanotubes with different nanotube diameters grown by a self-ordering process and
      subsequently treated with supercritical CO2 (ScCO2) fluid. We find that highly
      hydrophilic as-grown TiO2 nanotubes become hydrophobic after the ScCO2 treatment
      but can effectively recover their surface wettability under UV light irradiation
      as a result of photo-oxidation of C-H functional groups formed on the nanotube
      surface. It is demonstrated that human fibroblast cells show more obvious
      diameter-specific behavior on the ScCO2-treated TiO2 nanotubes than on the as
      grown ones in the range of diameters of 15 to 100 nm. This result can be
      attributed to the removal of disordered Ti(OH)4 precipitates from the nanotube
      surface by the ScCO2 fluid, thus resulting in purer nanotube topography and
      stronger diameter dependence of cell activity. Furthermore, for the smallest
      diameter of 15 nm, ScCO2-treated TiO2 nanotubes reveal higher biocompatibility
      than the as-grown sample.

PMID- 23547744
TI  - Renal denervation in a patient with two renal accessory arteries: a case report.
AB  - Percutaneous renal denervation has emerged as an effective adjunct in the
      management of resistant hypertension. However, the limits of the renal anatomical
      criteria that can be successfully treated are still unknown. In this report, we
      describe the case of a middle-aged man with essential resistant hypertension and
      two small left accessory renal arteries that underwent renal denervation of both
      principal renal arteries. He responded well with a progressive reduction in blood
      pressure measuring of 16/10, 32/17 and 45/24 mmHg at 1, 6 and 12 months,
      respectively. At 12 months, 94% of ambulatory measurements were below 140/90 mmHg
      and the number of anti-hypertensive medications had decreased from six to three.
      Thus, it would appear that the presence of two non-ablated left accessory renal
      arteries does not influence the response to renal denervation.

PMID- 23547745
TI  - N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the
      large swine.
AB  - CONTEXT: Sulfur mustard is a blister agent that can cause death by pulmonary
      damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has
      mucolytic and antioxidant actions and is an important pre-cursor of cellular
      glutathione synthesis. These actions may have potential to reduce mustard-induced
      lung injury. OBJECTIVE: Evaluate the effect of nebulised NAC as a post-exposure
      treatment for inhaled sulfur mustard in a large animal model. MATERIALS AND
      METHODS: Fourteen anesthetized, surgically prepared pigs were exposed to sulfur
      mustard vapor (100 MUg.kg-1), 10 min) and monitored, spontaneously breathing, to
      12 h. Control animals had no further intervention (n = 6). Animals in the
      treatment group were administered multiple inhaled doses of NAC (1 ml of 200
      mg.ml-1 MucomystTM at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8).
      Cardiovascular and respiratory parameters were recorded. Arterial blood was
      collected for blood gas analysis while blood and bronchoalveolar lavage fluid
      were collected for hematology and inflammatory cell analysis. Urine was collected
      to detect a sulfur mustard breakdown product. Lung tissue samples were taken for
      histopathological and post-experimental analyses. RESULTS: Five of six sulfur
      mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO2) and
      saturation levels were significantly decreased at 12 h. Arterial blood carbon
      dioxide (PaCO2) significantly increased, and arterial blood pH and bicarbonate
      (HCO3-) significantly decreased at 12 h. Shunt fraction was significantly
      increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8).
      There was significantly improved arterial blood oxygen saturation, HCO3- levels,
      and shunt fraction compared to those of the sulfur mustard controls. There were
      significantly fewer neutrophils and lower concentrations of protein in lavage
      compared to sulfur mustard controls. DISCUSSION: NAC's mucolytic and antioxidant
      properties may be responsible for the beneficial effects seen, improving
      clinically relevant physiological indices affected by sulfur mustard exposure.
      CONCLUSION: Beneficial effects of nebulized NAC were apparent following inhaled
      sulfur mustard exposure. Further therapeutic benefit may result from a
      combination therapy approach.

PMID- 23547747
TI  - The clinical effectiveness and cost-effectiveness of cetuximab (mono- or
      combination chemotherapy), bevacizumab (combination with non-oxaliplatin
      chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic
      colorectal cancer after first-line chemotherapy (review of technology appraisal
      No.150 and part review of technology appraisal No. 118): a systematic review and
      economic model.
AB  - BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in the
      UK after breast and lung cancer. People with metastatic disease who are
      sufficiently fit are usually treated with active chemotherapy as first- or second
      line therapy. Recently, targeted agents have become available including anti
      epidermal growth factor receptor (EGFR) agents, for example cetuximab and
      panitumumab, and anti-vascular endothelial growth factor (VEGF) receptor agents,
      for example bevacizumab. OBJECTIVE: To investigate the clinical effectiveness and
      cost-effectiveness of panitumumab monotherapy and cetuximab (mono- or combination
      chemotherapy) for Kirsten rat sarcoma (KRAS) wild-type (WT) patients, and
      bevacizumab in combination with non-oxaliplatin chemotherapy, for the treatment
      of metastatic colorectal cancer after first-line chemotherapy. DATA SOURCES: The
      assessment comprises a systematic review of clinical effectiveness and cost
      effectiveness studies, a review and critique of manufacturer submissions and a de
      novo cohort-based economic analysis. For the assessment of effectiveness, a
      literature search was conducted in a range of electronic databases, including
      MEDLINE, EMBASE and The Cochrane Library, from 2005 to November 2010. REVIEW
      METHODS: Studies were included if they were randomised controlled trials (RCTs)
      or systematic reviews of RCTs of cetuximab, bevacizumab or panitumumab in
      participants with EGFR-expressing metastatic colorectal cancer with KRAS WT
      status that has progressed after first-line chemotherapy (for cetuximab and
      panitumumab) or participants with metastatic colorectal cancer that has
      progressed after first-line chemotherapy (bevacizumab). All steps in the review
      were performed by one reviewer and checked independently by a second. Synthesis
      was mainly narrative. An economic model was developed focusing on third-line and
      subsequent lines of treatment. Costs and benefits were discounted at 3.5% per
      annum. Probabilistic and univariate deterministic sensitivity analyses were
      performed. RESULTS: The searches identified 7745 titles and abstracts. Two
      clinical trials (reported in 12 papers) were included. No data were available for
      bevacizumab in combination with non-oxaliplatin-based chemotherapy in previously
      treated patients. Neither of the included studies had KRAS status performed
      prospectively, but the studies did report retrospective analyses of the results
      for the KRAS WT subgroups. Third-line treatment with cetuximab plus best
      supportive care or panitumumab plus best supportive care appears to have
      statistically significant advantages over treatment with best supportive care
      alone in patients with KRAS WT status. For the economic evaluation, five studies
      met the inclusion criteria. The base-case incremental cost-effectiveness ratio
      (ICER) for KRAS WT patients for cetuximab compared with best supportive care is
      L98,000 per quality-adjusted life-year (QALY), for panitumumab compared with best
      supportive care is L150,000 per QALY and for cetuximab plus irinotecan compared
      with best supportive care is L88,000 per QALY. All ICERs are sensitive to
      treatment duration. LIMITATIONS: In the specific populations of interest, there
      is a lack of evidence on bevacizumab, cetuximab and cetuximab plus irinotecan
      used second line and on bevacizumab and cetuximab plus irinotecan used third
      line. For cetuximab plus irinotecan treatment for KRAS WT people, there is no
      direct evidence on progression-free survival, overall survival and duration of
      treatment. CONCLUSIONS: Although cetuximab and panitumumab appear to be
      clinically beneficial for KRAS WT patients compared with best supportive care,
      they are likely to represent poor value for money when judged by cost
      effectiveness criteria currently used in the UK. It would be useful to conduct a
      RCT for patients with KRAS WT status receiving cetuximab plus irinotecan.
      FUNDING: The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 23547746
TI  - Characterization of in vivo chemoresistant human hepatocellular carcinoma cells
      with transendothelial differentiation capacities.
AB  - BACKGROUND: Chemotherapeutic treatment of hepatocellular carcinoma often leads to
      chemoresistance during therapy or upon relapse of tumors. For the development of
      better treatments a better understanding of biochemical changes in the resistant
      tumors is needed. In this study, we focus on the characterization of in vivo
      chemoresistant human hepatocellular carcinoma HUH-REISO established from a
      metronomically cyclophosphamide (CPA) treated HUH7 xenograft model. METHODS: SCID
      mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every
      six days. Tumors were evaluated by immunohistochemistry, a functional blood-flow
      Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4,
      Sox-2 and Nanog mRNA levels. Cell lines of these tumors were analyzed by qRT-PCR
      and in endothelial transdifferentiation studies on matrigel. RESULTS: HUH-REISO
      cells, although slightly more sensitive against activated CPA in vitro than
      parental HUH-7 cells, fully retained their in vivo CPA chemoresistance upon
      xenografting into SCID mice. Histochemical analysis of HUH-REISO tumors in
      comparison to parental HUH-7 cells and passaged HUH-PAS cells (in vivo passaged
      without chemotherapeutic pressure) revealed significant changes in host
      vascularization of tumors and especially in expression of the tumor-derived human
      endothelial marker gene PECAM-1/CD31 in HUH-REISO. In transdifferentiation
      studies with limited oxygen and metabolite diffusion, followed by a matrigel
      assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential
      and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. A
      comparative study on stemness and plasticity markers revealed upregulation of Thy
      1, Oct-4, Sox-2 and Nanog in resistant xenografts. Under therapeutic pressure by
      CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3
      expression. CONCLUSIONS: Chemoresistance of HUH-REISO was not manifested under
      standard in vitro but under in vivo conditions. HUH-REISO cells showed increased
      pluripotent capacities and the ability of transdifferentiation to endothelial
      like cells in vitro and in vivo. These cells expressed typical endothelial
      surface marker and functionality. Although the mechanism behind chemoresistance
      of HUH-REISO and involvement of plasticity remains to be clarified, we
      hypothesize that the observed Notch regulations and upregulation of stemness
      genes in resistant xenografts are involved in the observed cell plasticity.

PMID- 23547749
TI  - Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice
      after cola beverages drinking.
AB  - BACKGROUND: Atherosclerosis is a major health burden. Metabolic disorders had
      been associated with large consumption of soft drinks. The rising incidence of
      atherosclerosis and metabolic alterations warrants the study of long-term soft
      drink consumption' effects on metabolism and atherosclerosis in genetic
      deficiency of apolipoprotein E which typically develops spontaneous
      atherosclerosis and metabolic alterations. METHODS: ApoE-/- mice were randomized
      in 3 groups accordingly with free access to: water (W), regular cola (C) or light
      cola (L). After 8 weeks, 50% of the animals in each group were euthanized (
      TREATMENT: W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks
      and were euthanized (Washout: W16, C16, L16). Body weight and food and drink
      consumption were periodically measured. Blood was collected (biochemistry). At
      autopsy, transverse aortic sinus sections were serially cut and stained
      (histomorphometry); livers and kidneys were processed (microscopy). MANOVA
      (identification of variance factors) was followed by ANOVA and LSD tests (within
      factor differences between levels). Conventionally a p< 0.05 was considered
      significant. RESULTS: TREATMENT increased drinking volumes (vs W8: 4 fold C8,
      p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (-54%, p<0.05 vs W8).
      I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non
      HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (-15%, p<0.05 vs W8)
      and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate
      aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7
      fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%,
      p<0.03) developed over time of study (age). II). TREATMENT caused plaque area
      increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and
      68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16:
      71% C16, p<0.01 and 46% L16, p<0.04). Age also caused plaque area increase (56%,
      p<0.04). TREATMENT- and age-effects on plaque enlargement were additive.
      CONCLUSION: Cola beverages caused atherosclerotic lesions' enlargement with
      metabolic (C) or non metabolic disturbances (L). ApoE-/- mice were particularly
      sensitive to L treatment. These findings may likely relate to caramel colorant
      and non-nutritive sweeteners in cola drinks and have potential implications in
      particularly sensitive individuals.

PMID- 23547750
TI  - Synchronizing microelectrode and electronic goniometer data using a pseudo-random
      binary signal.
AB  - Intra-operative investigation of the subthalamic nucleus (STN) requires
      concurrent measurement of microelectrode voltage, electrode depth and joint
      movement during deep brain stimulation (DBS) surgery. Commercial solutions to
      this problem exist but are more expensive. Multiple instruments from different
      manufacturers can collect the same data, but data from incompatible instruments
      are collected on disparate clocks, precluding quantitative analysis. A pseudo
      random binary signal recorded simultaneously by each set of instruments allows
      for chronological reconciliation. A custom program collects microelectrode data
      while simultaneously sending a pseudo-random binary signal to instruments
      measuring joint movement. The record of this signal is later used to express
      microelectrode voltage and joint position in a single chronological frame of
      reference. ClockSynch was used in 15 DBS procedures. After each surgery, records
      of microelectrode and joint movement were successfully chronologically
      reconciled. In conclusion, a pseudo-random binary signal integrates disparate
      systems of instrumentation at a significantly decreased cost.

PMID- 23547751
TI  - Probing from both sides: reshaping the graphene landscape via face-to-face dual
      probe microscopy.
AB  - In two-dimensional samples, all atoms are at the surface and thereby exposed for
      probing and manipulation by physical or chemical means from both sides. Here, we
      show that we can access the same point on both surfaces of a few-layer graphene
      membrane simultaneously, using a dual-probe scanning tunneling microscopy (STM)
      setup. At the closest point, the two probes are separated only by the thickness
      of the graphene membrane. This allows us for the first time to directly measure
      the deformations induced by one STM probe on a free-standing membrane with an
      independent second probe. We reveal different regimes of stability of few-layer
      graphene and show how the STM probes can be used as tools to shape the membrane
      in a controlled manner. Our work opens new avenues for the study of mechanical
      and electronic properties of two-dimensional materials.

PMID- 23547753
TI  - Depression and serotonin: a never ending story.

PMID- 23547754
TI  - Genetics of serotonin receptors and depression: state of the art.
AB  - Major depression (MD) is a major health problem, partly due to the incomplete
      understanding of the pathogenic mechanisms of the disease. Research efforts have
      mainly focused on alterations in monoaminergic neurotransmission, especially in
      relation to the serotonergic system, due to its key role in the regulation of
      mood and related biological functions. Given the high heritability of MD
      (estimated between 31% and 42% for unipolar depression), genes coding for key
      regulators of the serotonergic neurotransmission have been considered as optimal
      candidates. The present review is focused on the role of genes coding for
      serotonin receptors in MD pathogenesis, since the serotonin transporter and
      enzymes involved in serotonin metabolism have been reviewed elsewhere. Despite
      the large number of candidate gene studies focusing on genes coding for serotonin
      receptors, results have been inconsistent. The most replicated findings are the
      associations between rs6295 (HTR1A gene) G allele or G/G genotype and rs6311
      (HTR2A gene) A allele or A/A genotype and MD or depressive symptoms. Preclinical
      and imaging/post-mortem studies in humans provide strong support for the
      involvement of HTR1A and HTR2A genes in MD. Nevertheless, the inconsistency
      across previous studies clearly suggests that innovative approaches should be
      designed in order to overcome the limitations of candidate gene studies. To date,
      the most appealing methodologies seem to be full exome or genome sequencing,
      genome-wide pathway analyses, endophenotypes, and epigenetic biomarkers. The
      reported tools may assist in the detection of multiple-loci models, which could
      potentially explain the high percentage of MD susceptibility ascribed to genetic
      factors.

PMID- 23547755
TI  - Progress in structure-based design of EGFR inhibitors.
AB  - Epidermal growth factor receptors (EGFRs) belong to the ErbB family of receptor
      tyrosine kinases (TKs) involved in the proliferation of normal and malignant
      cells. As mutations and overexpression of ErbB TKs are implicated in carcinoma
      and glioblastoma and are related to both a very strong resistance to chemotherapy
      and a poor survival means that ErbB receptors are targets of considerable
      importance for anti-cancer drug design. Besides using monoclonal antibodies for
      anti-EGFR-related cancer therapeutics, small molecules - tyrosine kinase
      inhibitors are being considered as well. Some of these therapies have entered
      clinical trials or have been approved for clinical use. Based on experimental
      methods (radiometry, immunofluoroscence or luminescence, electrophoresis) that
      are mainly employed for measuring and interpreting the selectivity of protein
      kinase inhibitors, routine accomplishment of selectivity of small molecules for
      particular protein kinases is a substantial challenge. In light of this, we
      herein elaborate a computer-based protein engineering approach demonstrating its
      potential to be a viable supplement to experiment in modulating the affinity of
      ligand molecules for EGFR in an efficient manner. The structural basis of the
      remarkable strategy is also elucidated using our recent results obtained by means
      of molecular docking and molecular dynamics simulations. A few critical
      implications for successful structure-based design of prospective drug candidates
      against EGFR-related cancers are consequently discussed.

PMID- 23547756
TI  - "On-the-fly" kinetics of enzymatic racemization using deuterium NMR in DNA-based
      chiral oriented media.
AB  - We report the in situ and real-time monitoring of the interconversion of L- and D
      alanine-d3 by alanine racemase from Bacillus stearothermophilus directly observed
      by (2)H NMR spectroscopy in anisotropic phase. The enantiomers are distinguished
      by the difference of their (2)H quadrupolar splittings in a chiral liquid crystal
      containing short DNA fragments. The proof-of-principle, the reliability, and the
      robustness of this new method is demonstrated by the determination of the
      turnover rates of the enzyme using the Michaelis-Menten model.

PMID- 23547757
TI  - Potent proteasome inhibitors derived from the unnatural cis-cyclopropane isomer
      of Belactosin A: synthesis, biological activity, and mode of action.
AB  - The natural product belactosin A (1) with a trans-cyclopropane structure is a
      useful prototype compound for developing potent proteasome (core particle, CP)
      inhibitors. To date, 1 and its analogues are the only CP ligands that bind to
      both the nonprimed S1 pocket as well as the primed substrate binding channel;
      however, these molecules harbor a high IC50 value of more than 1 MUM. We have
      performed structure-activity relationship studies, thereby elucidating unnatural
      cis-cyclopropane derivatives of 1 that exhibit high potency to primarily block
      the chymotrypsin-like active site of the human constitutive (cCP) and
      immunoproteasome (iCP). The most active compound 3e reversibly inhibits cCP and
      iCP similarly with an IC50 of 5.7 nM. X-ray crystallographic analysis of the
      yeast proteasome in complex with 3e revealed that the ligand is accommodated
      predominantly into the primed substrate binding channel and covalently binds to
      the active site threonine residue via its beta-lactone ring-opening.

PMID- 23547758
TI  - Germ-line DICER1 mutations do not make a major contribution to the etiology of
      familial testicular germ cell tumours.
AB  - BACKGROUND: The RNase III enzyme DICER1 plays a central role in maturation of
      microRNAs. Identification of neoplasia-associated germ-line and somatic mutations
      in DICER1 indicates that mis-expression of miRNAs in cancer may result from
      defects in their processing. As part of a recent study of DICER1 RNase III
      domains in 96 testicular germ cell tumors, a single RNase IIIb domain mutation
      was identified in a seminoma. To further explore the importance of DICER1
      mutations in the etiology of testicular germ cell tumors (TGCT), we studied germ
      line DNA samples from 43 probands diagnosed with familial TGCT. FINDINGS: We
      carried out High Resolution Melting Curve Analysis of DICER1 exons 2-12, 14-19,
      21 and 24-27. All questionable melt curves were subjected to confirmatory Sanger
      sequencing.Sanger sequencing was used for exons 13, 20, 22 and 23. Intron-exon
      boundaries were included in all analyses. We identified 12 previously reported
      single nucleotide polymorphisms and two novel single nucleotide variants. No
      likely deleterious variants were identified; notably no mutations that were
      predicted to truncate the protein were identified. CONCLUSIONS: Taken together
      with previous studies, the findings reported here suggest a very limited role for
      either germ-line or somatic DICER1 mutations in the etiology of TGCT.

PMID- 23547760
TI  - Evaluation of inter-fraction and intra-fraction errors during volumetric
      modulated arc therapy in nasopharyngeal carcinoma patients.
AB  - BACKGROUND: This prospective study was conducted to evaluate inter- and intra
      fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric
      modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to
      thus obtain planning target volume (PTV) margins to effectively guide treatment
      in the future. METHODS: Fifteen NPC patients scheduled to undergo VMAT were
      prospectively enrolled in the study. For each patient, three CBCT scans were
      obtained; one after daily conventional positioning, one after online correction
      with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were
      registered to the planning CT to determine the inter- and intra-fraction errors.
      Patient positioning errors were analyzed for time trends over the course of
      radiotherapy. PTV margins were calculated from the systematic (Sigma) and random
      (sigma) errors. RESULTS: The average absolute values of the pre-correction, post
      correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the
      medial-lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior-inferior (SI)
      direction and 1.1, 0.7 and 0.5 mm in the anterior-posterior (AP) direction. The
      corresponding Sigma were 1.0-1.4 mm, 0.4-0.5 mm and 0.2-0.4 mm, while the
      corresponding sigma were 0.7-0.8 mm, 0.6-0.7 mm and 0.5-0.6 mm. With time,
      gradual increases in both the inter- and intra-fraction three-dimensional
      displacements were observed (P = 0.019 and P = 0.044, respectively). The total
      PTV margins accounting for pre-correction and intra-fraction errors were 3.4-4.1
      mm and those accounting for post-correction and intra-fraction errors were 1.7
      2.2 mm. CONCLUSIONS: CBCT is an effective modality to evaluate and improve the
      accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional
      displacements increased as a function of time during the course of radiotherapy.
      In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing
      VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans.

PMID- 23547761
TI  - Ceramide-2 nanovesicles for effective transdermal delivery: development,
      characterization and pharmacokinetic evaluation.
AB  - Abstract Context: The vesicles based on skin lipid have a drug localization
      effect and its main lipid, ceramide provides protective and regenerative effects
      while oleic acid (OA) is a penetration enhancer, however, it causes slight
      irritation, so we have formulated formulation incorporating both of these to
      develop a transdermal formulation for better permeation. OBJECTIVE: Present study
      investigated the preparation and characterization of physicochemical properties
      and permeation of nanovesicles of ceramide-2 containing OA and palmitic acid (PA)
      respectively and a commercial gel. MATERIALS AND METHODS: The vesicles were made
      using ceramide 2, cholesterol (Chol), cholesteryl sulfate (CS) and OA or PA,
      respectively, using film hydration method. The vesicles were characterized for
      physicochemical properties, ex vivo permeation using human skin and
      pharmacokinetic parameters and anti-inflammatory activity in rats. RESULTS: The
      vesicles showed size at 102-125 nm while PDI was 0.11-0.13 and negative zeta
      potential. OV-3 showed highest entrapment efficiency. The drug fluxes were 92.02
      and 8.920 MUg/cm(2)/h, respectively, for OV-3 and PV-1. The Cmax were 7.91 and
      4.01 MUg/ml at 4 and 6 h for OV-3 (2.5 mg) and PV-1 (10 mg), respectively. OV-3
      and PV-1 showed 98.8% and 77.36% edema inhibition, respectively, at 3 h.
      DISCUSSION: Both formulations showed similar physical parameters and different
      permeation since OA get incorporated in vesicles and increases its permeability
      and ceramide makes sure that vesicles can rapidly traverse the stratum corneum.
      CONCLUSION: OV-3 containing 3% OA showed optimum physical parameters and good
      permeation with maximum anti-inflammatory activity.

PMID- 23547762
TI  - Budesonide/cyclodextrin complex-loaded lyophilized microparticles for intranasal
      application.
AB  - OBJECTIVE: Lyophilized microparticles composed of budesonide (BDS), hydroxypropyl
      beta-cyclodextrin (HP-beta-CD), and hydroxypropylmethylcellulose (HPMC) or sodium
      carboxymethylcellulose (CMC-Na) were developed for intranasal delivery and their
      characteristics were evaluated. MATERIALS AND METHODS: The particle size and
      morphology were assessed by mean diameter measurement and scanning electron
      microscopy (SEM) image, respectively. The solid-state of products was tested by X
      ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR)
      and differential scanning calorimetry (DSC). In vitro drug release and
      cytotoxicity to the primary human nasal epithelial (HNE) cells were also
      evaluated. RESULTS AND DISCUSSION: Lyophilized microparticles exhibited
      vanishment of crystallinity of drug in XRPD analysis, the enfeeblement of
      carbonyl (C=O) stretching bands of carboxyl group in BDS in FT-IR spectra and the
      disappearance of endothermic peak of drug in the results of DSC study. Based on
      the results of solid-state studies, BDS was existed as an amorphous form in the
      lyophilized microparticles. CD complexation enhanced drug solubility and release
      rate, and HPMC or CMC-Na also improved drug dissolution rates. Cytotoxicity of
      developed microparticles to the HNE cells was measured and their safety to HNE
      cell was identified. CONCLUSION: Developed microparticles can efficiently deliver
      insoluble drug, such as BDS, to the nasal epithelium and thus it may improve
      therapeutic efficacy in the respiratory tract.

PMID- 23547759
TI  - Synthesis and SAR of Lehualide B: a marine-derived natural product with potent
      anti-multiple myeloma activity.
AB  - We report a concise and convergent laboratory synthesis of the rare marine
      natural product lehualide B that has led to the discovery that (1) this compound
      has low nanomolar activity against human multiple myeloma cells and (2) the
      anticancer effects of lehualide B and its analogues are selective (i.e., they are
      approximately 2-3 orders of magnitude less toxic to human breast cancer cells).
      Synthetic lehualide B is shown to be an effective inhibitor of complex I of the
      mitochondrial electron transport chain, with potency similar to that observed for
      the terrestrial natural products piericidin A1 and rotenone, an observation that
      led to the discovery that piericidin A1 is also selectively cytotoxic toward
      human multiple myeloma cells. Interestingly, synthetic derivatives of lehualide B
      that resemble verticipyrone (an established complex I inhibitor composed of a
      gamma-pyrone and a simple monounsaturated hydrophobic chain) lack the potent
      antimyeloma activity of the natural product. Finally, the synthesis and
      evaluation of a collection of lehualide-inspired analogues led to the elucidation
      of structure-activity relationships for this rare natural product that
      established important roles for the substituted gamma-pyrone headgroup and the
      skipped polyene side chain. 

PMID- 23547763
TI  - Metal-assisted chemical etching of Ge(100) surfaces in water toward nanoscale
      patterning.
AB  - We propose the metal-assisted chemical etching of Ge surfaces in water mediated
      by dissolved oxygen molecules (O2). First, we demonstrate that Ge surfaces around
      deposited metallic particles (Ag and Pt) are preferentially etched in water. When
      a Ge(100) surface is used, most etch pits are in the shape of inverted pyramids.
      The mechanism of this anisotropic etching is proposed to be the enhanced
      formation of soluble oxide (GeO2) around metals by the catalytic activity of
      metallic particles, reducing dissolved O2 in water to H2O molecules. Secondly, we
      apply this metal-assisted chemical etching to the nanoscale patterning of Ge in
      water using a cantilever probe in an atomic force microscopy setup. We
      investigate the dependences of probe material, dissolved oxygen concentration,
      and pressing force in water on the etched depth of Ge(100) surfaces. We find that
      the enhanced etching of Ge surfaces occurs only when both a metal-coated probe
      and saturated-dissolved-oxygen water are used. In this study, we present the
      possibility of a novel lithography method for Ge in which neither chemical
      solutions nor resist resins are needed. 

PMID- 23547764
TI  - MGcV: the microbial genomic context viewer for comparative genome analysis.
AB  - BACKGROUND: Conserved gene context is used in many types of comparative genome
      analyses. It is used to provide leads on gene function, to guide the discovery of
      regulatory sequences, but also to aid in the reconstruction of metabolic
      networks. We present the Microbial Genomic context Viewer (MGcV), an interactive,
      web-based application tailored to strengthen the practice of manual comparative
      genome context analysis for bacteria. RESULTS: MGcV is a versatile, easy-to-use
      tool that renders a visualization of the genomic context of any set of selected
      genes, genes within a phylogenetic tree, genomic segments, or regulatory
      elements. It is tailored to facilitate laborious tasks such as the interactive
      annotation of gene function, the discovery of regulatory elements, or the
      sequence-based reconstruction of gene regulatory networks. We illustrate that
      MGcV can be used in gene function annotation by visually integrating information
      on prokaryotic genes, like their annotation as available from NCBI with other
      annotation data such as Pfam domains, sub-cellular location predictions and gene
      sequence characteristics such as GC content. We also illustrate the usefulness of
      the interactive features that allow the graphical selection of genes to
      facilitate data gathering (e.g. upstream regions, ID's or annotation), in the
      analysis and reconstruction of transcription regulation. Moreover, putative
      regulatory elements and their corresponding scores or data from RNA-seq and
      microarray experiments can be uploaded, visualized and interpreted in (ranked-)
      comparative context maps. The ranked maps allow the interpretation of predicted
      regulatory elements and experimental data in light of each other. CONCLUSION:
      MGcV advances the manual comparative analysis of genes and regulatory elements by
      providing fast and flexible integration of gene related data combined with
      straightforward data retrieval. MGcV is available at http://mgcv.cmbi.ru.nl.

PMID- 23547765
TI  - Long term effects of a health promotion intervention in low socioeconomic Arab-
      Israeli kindergartens.
AB  - BACKGROUND: Obesity is the most common chronic pediatric disease in westernized,
      especially low socioeconomic societies. We previously demonstrated the beneficial
      effects of a randomized prospective school-based health education program for low
      socioeconomic status Arab-Israeli kindergarten children. METHODS: To examine
      whether the effects of our program on nutrition and physical activity knowledge
      and preferences, anthropometric measures, and fitness persisted one year after
      the end of intervention. RESULTS: At one year following the intervention BMI and
      BMI percentiles approached baseline level in both the intervention (16.4 +/- 0.2
      kg/m2 and 61.5 +/- 2.4%, respectively) and control group participants (16.5 +/-
      0.2 kg/m2 and 58.5 +/- 3.3%, respectively). Yet, a year after the end of the
      intervention, the decrease in BMI%ile from baseline was significantly greater in
      the intervention group (-7.8 +/- 1.5 vs. -1.9 +/- 1.9, p<0.012). Nutritional and
      physical activity knowledge and preferences, and physical fitness remained
      significantly elevated in the intervention compared to the control group
      participants. CONCLUSIONS: The beneficial effects of a kindergarten dietary
      physical activity intervention applied by the kindergarten teachers, on nutrition
      and physical activity knowledge and preferences, fitness, and BMI percentile were
      evident one year after the end of intervention. This promising program may play a
      role in health promotion, prevention and treatment of childhood obesity.

PMID- 23547766
TI  - The epidemiology of food allergy in Europe: protocol for a systematic review.
AB  - BACKGROUND: The European Academy of Allergy and Clinical Immunology is in the
      process of developing its Guideline for Food Allergy and Anaphylaxis, and this
      protocol of a systematic review is one of seven inter-linked evidence syntheses
      that are being undertaken in order to provide a state-of-the-art synopsis of the
      current evidence base in relation to epidemiology, prevention, diagnosis and
      clinical management and impact on quality of life, which will be used to inform
      the formulation of clinical recommendations.The aims of the systematic review
      will be to understand and describe the epidemiology of food allergy, i.e.
      frequency, risk factors and outcomes of patients suffering from food allergy, and
      to describe how these characteristics vary by person, place and time. METHODS: A
      highly sensitive search strategy has been developed to retrieve articles that
      have investigated the various aspects of the epidemiology of food allergy. The
      search will be implemented by combining the concepts of food allergy and its
      epidemiology from electronic bibliographic databases. DISCUSSION: This systematic
      review will provide the most up to date estimates of the frequency of food
      allergy in Europe. We will attempt to break these down by age and geographical
      region in Europe. Our analysis will take into account the suitability of the
      study design and the respective study biases that could affect exposure and
      outcome. We will examine the different methods to diagnose food allergy and the
      associated measures of occurrence.

PMID- 23547767
TI  - Is the relationship between pattern recall and decision-making influenced by
      anticipatory recall?
AB  - The present study compared traditional measures of pattern recall to measures of
      anticipatory recall and decision-making to examine the underlying mechanisms of
      expert pattern perception and to address methodological limitations in previous
      studies where anticipatory recall has generally been overlooked. Recall
      performance in expert and novice basketball players was measured by examining the
      spatial error in recalling player positions both for a target image (traditional
      recall) and at 40-ms increments following the target image (anticipatory recall).
      Decision-making performance was measured by comparing the participant's response
      to those identified by a panel of expert coaches. Anticipatory recall was
      observed in the recall task and was significantly more pronounced for the
      experts, suggesting that traditional methods of spatial recall analysis may not
      have provided a completely accurate determination of the full magnitude of the
      experts' superiority. Accounting for anticipatory recall also increased the
      relative contribution of recall skill to decision-making accuracy although the
      gains in explained variance were modest and of debatable functional significance.

PMID- 23547768
TI  - Kinetics and mechanism of the alkaline decomposition of hexathionate ion.
AB  - The alkaline decomposition of hexathionate has been investigated by high
      performance liquid chromatography monitoring the concentration of polythionates
      (such as hexathionate, pentathionate, and tetrathionate) and that of thiosulfate
      simultaneously in buffered medium at a constant ionic strength. As a major final
      product, unlike in the case of the alkaline decomposition of tetrathionate and
      pentathionate, a significant amount of sulfur deposition was also observed.
      Nevertheless, the chromatograms clearly suggested that heptathionate also appears
      as a key intermediate in a detectable amount during the course of the reaction.
      On the basis of these observations an 11-step kinetic model with 9 fitted and 4
      fixed rate coefficients is suggested to take all of the most important
      characteristics of the decomposition into account. The proposed model includes
      the well-known thiosulfate-assisted sulfur chain, increasing pathways for
      tetrathionate and pentathionate along with their rate coefficients, but among
      them that of the thiosulfate-assisted rearrangement of pentathionate has not been
      reported yet. Having these kinetic parameters in hand reveals a reasonable trend
      of these rate coefficients against the length of the sulfur chain, suggesting
      that the attack of the nucleophilic agents like hydroxide, thiosulfate, and
      sulfite ions is determined by the electron density in the vicinity of the given
      sulfur atom.

PMID- 23547770
TI  - Numerical simulation of proton distribution with electric double layer in
      extended nanospaces.
AB  - Understanding the properties of liquid confined in extended nanospaces (10-1000
      nm) is crucial for nanofluidics. Because of the confinement and surface effects,
      water may have specific structures and reveals unique physicochemical properties.
      Recently, our group has developed a super resolution laser-induced fluorescence
      (LIF) technique to visualize proton distribution with the electrical double layer
      (EDL) in a fused-silica extended nanochannel (Kazoe, Y.; Mawatari, K.; Sugii, Y.;
      Kitamori, T. Anal. Chem.2011, 83, 8152). In this study, based on the coupling of
      the Poisson-Boltzmann theory and site-dissociation model, the effect of specific
      water properties in an extended nanochannel on formation of EDL was investigated
      by comparison of numerical results with our previous experimental results. The
      numerical results of the proton distribution with a lower dielectric constant of
      approximately 17 were shown to be in good agreement with our experimental
      results, which confirms our previous observation showing a lower water
      permittivity in an extended nanochannel. In addition, the higher silanol
      deprotonation rate in extended nanochannels was also demonstrated, which is
      supported by our previous results of NMR and streaming current measurements. The
      present results will be beneficial for a further understanding of interfacial
      chemistry, fluid physics, and electrokinetics in extended nanochannels. 

PMID- 23547769
TI  - Estimating relative intensity using individualized accelerometer cutpoints: the
      importance of fitness level.
AB  - BACKGROUND: Accelerometer cutpoints based on absolute intensity may under or
      overestimate levels of physical activity due to the lack of consideration for an
      individual's current fitness level. The purpose of this study was to illustrate
      the interindividual variability in accelerometer activity counts measured at
      relative intensities (40 and 60% heart rate reserve (HRR)) and demonstrate the
      differences between relative activity counts between low, moderate and high
      fitness groups. METHODS: Seventy-three subjects (38 men, 35 women) with a wide
      range of cardiorespiratory fitness (maximal oxygen consumption (VO2max): 27.9 to
      58.5 ml . kg-1 . min-1), performed a submaximal exercise test with measures of
      heart rate (HR) and accelerometer activity counts. Linear regression equations
      were developed for each subject to determine accelerometer activity counts for
      moderate and vigorous intensity physical activity corresponding to 40% and 60% of
      HRR. Interindividual variability of activity counts between subjects at both 40%
      and 60% of HRR was demonstrated by plotting values using a box and whisker plot.
      To examine the difference between absolute and relative activity cutpoints,
      subjects were categorized into 3 fitness groups based on metabolic equivalents
      (MET) (<10 MET, 10-13 MET, >13 MET). RESULTS: At 40 and 60% of HRR, activity
      counts ranged from 1455-7520, and 3459-10066 counts . min-1, respectively.
      Activity counts at 40% HRR (3385 +/- 850, 4048 +/- 1090, and 5037 +/- 1019 counts
      . min-1) and 60% HRR (5159 +/- 765, 5995 +/- 1131 and 7367 +/- 1374 counts . min
      1) significantly increased across fitness groups (<10 MET, 10-13 MET, and >13
      MET, respectively). CONCLUSION: This study revealed interindividual variability
      in activity counts at relative moderate (40% HRR) and vigorous (60% HRR)
      intensities, while fitness level was shown to have a significant influence on
      relative activity counts measured at these intensities. Individualizing activity
      count cutpoints may be more representative of an individual's PA level relative
      to their fitness capacity, compared to absolute activity count cutpoints.

PMID- 23547771
TI  - Chemically modulated graphene diodes.
AB  - We report the manufacture of novel graphene diode sensors (GDS), which are
      composed of monolayer graphene on silicon substrates, allowing exposure to
      liquids and gases. Parameter changes in the diode can be correlated with charge
      transfer from various adsorbates. The GDS allows for investigation and tuning of
      extrinsic doping of graphene with great reliability. The demonstrated recovery
      and long-term stability qualifies the GDS as a new platform for gas,
      environmental, and biocompatible sensors.

PMID- 23547772
TI  - Transient ischaemic attack and ischaemic stroke: constructing episodes of care
      using hospital claims data.
AB  - BACKGROUND: Stroke patients may have multiple hospital separations relating to
      the same stroke. Understanding the pattern of hospitalisations for these patients
      enables first and recurrent events to be distinguished to better understand care.
      The aim of this study was to investigate reasons for hospital separations after
      transient ischaemic attack (TIA) or ischaemic stroke and construct episode of
      care criteria. METHODS: A retrospective observational study was conducted using
      the Australian Government Department of Veterans' Affairs administrative claims
      database. All patients hospitalised for TIA or ischaemic stroke in 2008-2009 were
      included. Reasons for hospital separations in the 60 days after TIA or ischaemic
      stroke were classified by a clinical panel as 'probably', 'possibly' or
      'unlikely' to be related to the index separation. Based on panel assessment and
      time between separations, episode of care criteria for TIA and ischaemic stroke
      were constructed. RESULTS: Of the 4520 veterans alive after the index separation,
      32% of TIA patients (n=782) and 63% of ischaemic stroke patients (n=1323) had
      another separation within 60 days. The clinical panel reviewed 460 unique reasons
      for readmission. Of the 3263 separations, 55% and 85% were classified as related
      to the index TIA and ischaemic stroke separation, respectively. CONCLUSIONS:
      Patients hospitalised for ischaemic stroke are likely to have multiple hospital
      separations for treatment of the same event. Multiple separations for treatment
      of TIA were less frequent. Consideration of these related separations is
      recommended when assessing health service utilisation from claims databases.

PMID- 23547773
TI  - Effective treatment with a tetrandrine/chloroquine combination for chloroquine
      resistant falciparum malaria in Aotus monkeys.
AB  - BACKGROUND: In vitro evidence indicates that tetrandrine (TT) can potentiate the
      action of chloroquine 40-fold against choloquine-resistant Plasmodium falciparum.
      The key question emanating from that study is "would tetrandine and chloroquine
      be highly effective in a live Aotus monkey model with chloroquine-resistant
      parasites". This study was designed to closely mimic the pharmacological/anti
      malarial activity in man. METHODS: The Vietnam Smith/RE strain of P. falciparum,
      which is chloroquine-resistant was used in this study. Previous experimental
      procedures were followed. Panamanian owl monkeys (Aotus) were inoculated with
      5*10(6) erythrocytes parasitized with the CQ-resistant strain of P. falciparum.
      Oral drug treatment was with CQ (20 mg/kg) and/or tetrandrine at 15 mg/Kg, 30
      mg/Kg or 60 mg/Kg or 25 mg/Kg depending on experimental conditions. RESULTS AND
      DISCUSSION: Parasitaemia was cleared rapidly with CQ and TT while CQ treatment
      alone was ineffective. Recrudescence of malaria occurred after seven days post
      infection. However, four animals were treated orally with TT and CQ parasites
      were cleared. It is likely that monkeys were cured via a combination of both drug
      and host immune responses. A single Aotus monkey infected with P. falciparum and
      untreated with drugs, died. No side effects were observed with these drug
      treatments. CONCLUSIONS: This combination of chloroquine and tetrandrine forms
      the basis of a new attack on chloroquine-resistant malaria - one based upon
      inhibition of the basis of chloroquine resistance, the multiple drug resistance
      pump. Previous studies demonstrated that the parasite MDR pump was found on
      parasite membranes using 3H azidopine photoaffinity labelling.Since MDR-based
      choloroquine resistance is induced by chloroquine, the basis of the action of
      tetrandrine is the following: 1) tetrandrine inhibits the MDR pump by stimulating
      MDR ATPase which limits the energy of the pump by depletion of parasite ATP, 2)
      tetrandrine blocks the genetic factor which controls the induction of the pump.
      Therefore, it appears that the parasite cannot outsmart these mechanisms and
      produce a new mode of resistance. Only time will tell if this is correct.

PMID- 23547774
TI  - Automated 24-hours sampling of subcutaneous tissue free cortisol in humans.
AB  - Hormonal systems are major regulators of metabolic and cognitive function and
      many of these, including the critical stress-responsive hypothalamic-pituitary
      adrenal (HPA) axis, release their constituent hormones in a circadian manner.
      This circadian rhythmicity is made up from an underlying approximate hourly
      ultradian rhythm. In order to understand the importance of both circadian and
      ultradian rhythms in man it is important to be able to carry out multiple
      sampling studies over extended periods in a subject's home setting, which is the
      most meaningful physiological setting for homeostatically important hormones.
      This study has developed a novel automated sampling system that, when used in
      combination with a microdialysis system, collects timed samples of microdialysis
      fluid over a full 24 h in individuals going about their normal everyday activity.
      The apparatus has the capacity to provide sufficient sample volumes to measure
      changes in hormone concentration over 24 h, including the important period when
      subjects are asleep.

PMID- 23547775
TI  - Structural basis for inhibition of the fat mass and obesity associated protein
      (FTO).
AB  - The fat mass and obesity associated protein (FTO) is a potential target for anti
      obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid
      demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil,
      and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG
      analogues and related compounds using differential scanning fluorometry- and
      liquid chromatography-based assays. The results revealed sets of both cyclic and
      acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include
      small molecules that have been used in clinical studies for the inhibition of
      other 2OG oxygenases. Crystallographic analyses reveal inhibition by 2OG
      cosubstrate or primary substrate competitors as well as compounds that bind
      across both cosubstrate and primary substrate binding sites. The results will aid
      the development of more potent and selective FTO inhibitors.

PMID- 23547777
TI  - Incompatible quartets, triplets, and characters.
AB  - We study a long standing conjecture on the necessary and sufficient conditions
      for the compatibility of multi-state characters: There exists a function f(r)
      such that, for any set C of r-state characters, C is compatible if and only if
      every subset of f(r) characters of C is compatible. We show that for every r>=2,
      there exists an incompatible set C of Omega(r2)r-state characters such that every
      proper subset of C is compatible. This improves the previous lower bound of
      f(r)>=r given by Meacham (1983), and f(4)>=5 given by Habib and To (2011). For
      the case when r=3, Lam, Gusfield and Sridhar (2011) recently showed that f(3)=3.
      We give an independent proof of this result and completely characterize the sets
      of pairwise compatible 3-state characters by a single forbidden intersection
      pattern.Our lower bound on f(r) is proven via a result on quartet compatibility
      that may be of independent interest: For every n>=4, there exists an incompatible
      set Q of Omega(n2) quartets over n labels such that every proper subset of Q is
      compatible. We show that such a set of quartets can have size at most 3 when n=5,
      and at most O(n3) for arbitrary n. We contrast our results on quartets with the
      case of rooted triplets: For every n>=3, if R is an incompatible set of more than
      n-1 triplets over n labels, then some proper subset of R is incompatible. We show
      this bound is tight by exhibiting, for every n>=3, a set of n-1 triplets over n
      taxa such that R is incompatible, but every proper subset of R is compatible. 

PMID- 23547776
TI  - Development of an ALK2-biased BMP type I receptor kinase inhibitor.
AB  - The bone morphogenetic protein (BMP) signaling pathway has essential functions in
      development, homeostasis, and the normal and pathophysiologic remodeling of
      tissues. Small molecule inhibitors of the BMP receptor kinase family have been
      useful for probing physiologic functions of BMP signaling in vitro and in vivo
      and may have roles in the treatment of BMP-mediated diseases. Here we describe
      the development of a selective and potent inhibitor of the BMP type I receptor
      kinases, LDN-212854, which in contrast to previously described BMP receptor
      kinase inhibitors exhibits nearly 4 orders of selectivity for BMP versus the
      closely related TGF-beta and Activin type I receptors. In vitro, LDN-212854
      exhibits some selectivity for ALK2 in preference to other BMP type I receptors,
      ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling,
      transcriptional activity, and function. LDN-212854 potently inhibits heterotopic
      ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia
      ossificans progressiva. These findings represent a significant step toward
      developing selective inhibitors targeting individual members of the highly
      homologous BMP type I receptor family. Such inhibitors would provide greater
      resolution as probes of physiologic function and improved selectivity against
      therapeutic targets. 

PMID- 23547778
TI  - The effect of opportunistic illness on HIV RNA viral load and CD4+ T cell count
      among HIV-positive adults taking antiretroviral therapy.
AB  - INTRODUCTION: HIV RNA viral load (VL) has been shown to increase during
      opportunistic illnesses (OIs), suggesting active HIV replication in response to
      infection among patients not taking antiretroviral therapy (ART). We assessed the
      effects of OIs on HIV RNA VL and CD4+ T cell counts among patients on ART with
      initially suppressed VL. METHODS: Between 2003 and 2007, we enrolled and followed
      1094 HIV-1-infected adults who initiated ART and had quarterly blood draws for VL
      and CD4+ T cell count. In VL/CD4+ T cell measurement intervals following
      undetectable VL, we compared the elevation in VL to detectable levels and CD4+ T
      cell count changes between intervals when participants had episodes of OIs and
      intervals when they did not have OIs. RESULTS: VL was more likely to be
      detectable if participants had OIs in the prior three months compared to when
      they did not (OR=4.0 (95% CI=1.9-8.6)). The CD4+ T cell counts declined 24.1
      cells/uL per three months in intervals where the participants had OIs compared to
      an increase of 21.3 cells/uL per three months in intervals where they did not
      have OIs (adjusted difference in the rate of CD4+ T cell count change of 61.7
      cells/uL per three months (95% CI=13.7-109.7), P value=0.012). The rate of CD4+ T
      cell count increase was 25.6 cells/uL per three months (95% CI=11.6-39.6) higher
      for females compared to males (p value=<0.001), 1.4 cells/uL per three months
      lower per one year increase in age (p value=0.046) and 4 cells/uL per three
      months lower per 10 cells/uL increase in the starting CD4+ T cell count value (p
      value=<0.001). CONCLUSION: Episodes of opportunistic infections among patients
      taking ART with undetectable VL were associated with elevation of HIV RNA VL to
      detectable levels and decline in CD4+ T cell counts. CLINICAL TRIAL NUMBER:
      NCT00119093.

PMID- 23547779
TI  - Photodynamic inactivation of yeast and bacteria by extracts of Alternanthera
      brasiliana.
AB  - This study was undertaken to evaluate the effect of Alternathera brasiliana
      (Amaranthaceae) extracts as photosensitizing agents in photodynamic antimicrobial
      therapies (PACT) against Staphylococcus aureus, Staphylococcus epidermidis and
      Candida dubliniensis. The crude hexane and ethanol extracts were obtained from A.
      brasiliana whole plant and showed absortion from 650 to 700 nm. Also, singlet
      molecular oxygen (1O2) production (type II photosensitization reaction) was
      examined, and the results show that 1,3-diphenylisobenzofuran photodegradation
      was greatly enhanced in the presence of the A. brasiliana extracts. One plate in
      each assay was irradiated while the other was not irradiated, the number of
      colony-forming units per milliliter (CFU/mL) was obtained, and data analyzed by
      the Tukey test. The chemical composition of the extracts was determined by
      chromatographic and spectrometric techniques; steroids, triterpenes, and
      flavonoids were identified. Laser irradiation alone at 685 nm using diode laser,
      output power of 35 mW, and energy of 28 J/cm2, or non-irradiated crude extracts
      in sub-inhibitory concentration did not reduce the number of CFU/mL
      significantly, whereas irradiated hexane and ethanol extracts, in sub-inhibitory
      concentrations, inhibited the growth of these microorganisms. The photoactivation
      of hexane and ethanol extracts of A. brasiliana, in sub-inhibitory
      concentrations, using red laser radiation at 685 nm had an antimicrobial effect.

PMID- 23547780
TI  - Key targets and relevant inhibitors for the drug discovery of tuberculosis.
AB  - Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium
      tuberculosis (M. tuberculosis), killing about two million people worldwide each
      year. An increase in the prevalence of drug-resistant strains of M. tuberculosis
      in the past decades has renewed focus on the development of new drugs that can
      treat both drug-sensitive and resistant TB infections. M. tuberculosis evades the
      host immune system and drug regimes by entering dormant phase within macrophage.
      As a consequence, there is a pressing need for new vaccines and antimicrobials to
      treat persistent infections. As clinically used antibiotics target very few
      essential functions of mycobacterium, it is rational that identification of new
      targets that are essential for bacterial growth and survival can serve as
      starting point for designing of novel drugs to cure both drug-sensitive and
      resistant TB infections. With the development of molecular biology and structural
      biology and the availability of the genome sequence of M. tuberculosis, some
      success has been achieved in the identification of new targets in M. tuberculosis
      and their relevant inhibitors. This review summarizes about ninety important
      targets that participate in a range of diverse physiological processes in M.
      tuberculosis and seven new drugs currently in clinical phase 2 or 3 trials. In
      addition, promising inhibitors with novel mechanisms of action and clinical
      vaccine candidates are highlighted.

PMID- 23547781
TI  - Fabrication of Fe-Al nanoparticles by selective oxidation of Fe-Al thin films.
AB  - The possibility of a new technique for fabricating nanoparticles from thin films
      using selective oxidation in an atmosphere mixture of water vapor and hydrogen
      was investigated. Fe-5wt.%Al films were RF-sputtered and annealed in the
      atmosphere mixture at 900 degrees C for up to 200 min, in order to oxidize
      aluminum selectively. Thermodynamics simulation showed that temperatures
      exceeding 800 degrees C are necessary to prevent iron from being oxidized, as
      confirmed by the depth profile of XPS. As the annealing time increased, the
      morphology of the 200-nm Fe-Al films changed from the continuous to the
      discontinuous type; thus, particulate Fe-Al films formed after 100 min. The
      particulate 10- to 100-nm Fe-Al films showed super-paramagnetic behavior after
      the oxidation. Thus, a new technique for fabricating nanoparticles was
      successfully introduced using selective oxidation.

PMID- 23547782
TI  - Scaling up prevention of mother-to-child HIV transmission programs in sub-Saharan
      African countries: a multilevel assessment of site-, program- and country-level
      determinants of performance.
AB  - BACKGROUND: Uptake of prevention of mother-to-child HIV transmission (PMTCT)
      programs remains challenging in sub-Saharan Africa because of multiple barriers
      operating at the individual or health facility levels. Less is known regarding
      the influence of program-level and contextual determinants. In this study, we
      explored the multilevel factors associated with coverage in single-dose
      nevirapine PMTCT programs. METHODS: We analyzed aggregate routine data collected
      within the framework of the Viramune((r)) Donation Programme (VDP) from 269 sites
      in 20 PMTCT programs and 15 sub-Saharan countries from 2002 to 2005. Site
      performance was measured using a nevirapine coverage ratio (NCR), defined as the
      reported number of women receiving nevirapine divided by the number of women who
      should have received nevirapine (observed HIV prevalence x number of women in
      antenatal care [ANC]). Data on program-level determinants were drawn from the
      initial application forms, and country-level determinants from the Demographic
      and Health Surveys (DHS) and the World Bank (World Development Indicators).
      Multilevel linear mixed models were used to identify independent factors
      associated with NCR at the site-, program- and country-level. RESULTS: Of 283,410
      pregnant women attending ANC in the included sites, 174,312 women (61.5%)
      underwent HIV testing after receiving pre-test counselling, of whom 26,700 tested
      HIV positive (15.3%), and 22,591 were dispensed NVP (84.6%). Site performance was
      highly heterogeneous between and within programs. Mean NCR by site was 43.8%
      (interquartile range: 19.1-63.9). Multilevel analysis identified higher HIV
      prevalence (Beta coefficient: 25.1, 95% confidence interval [CI] 18.7 to 31.6),
      higher proportion of persons with knowledge of PMTCT (8.3; CI 0.5 to 16.0),
      higher health expenditure as a proportion of Gross Domestic Product (3.9 per %;
      CI 2.0 to 5.8) and lower percentage of rural population (-0.7 per %; CI -1.0 to 
      0.5) as significant country-level predictors of higher NCR at the p<0.05 level. A
      medium ANC monthly activity (30-100/month) was the only site-level predictor
      found (-7.6; CI -15.1 to -0.1). CONCLUSIONS: Heterogeneity of nevirapine coverage
      between sites and programs was high. Multilevel analysis identified several
      significant contextual determinants, which may warrant additional research to
      further define important multi-level and potentially modifiable determinants of
      performance of PMTCT programs.

PMID- 23547783
TI  - Genome-wide co-expression analysis predicts protein kinases as important
      regulators of phosphate deficiency-induced root hair remodeling in Arabidopsis.
AB  - BACKGROUND: Phosphorus (P) is one of the essential but often limiting elements
      for plants. Based on transcriptional profiling we reported previously that more
      than 3,000 genes are differentially expressed between phosphate (Pi)-deficient
      and Pi-sufficient Arabidopsis roots (MCP 11(11):1156-1166, 2012). The current
      study extends these findings by focusing on the analysis of genes that encode
      protein kinases (PK) and phosphatases (PP) by mining PK and PP genes that were
      differentially expressed in response to Pi deficiency. RESULTS: Subsets of 1,118
      and 205 annotated PK and PP genes were mined on the basis of the TAIR10 release
      of the Arabidopsis genome. Analysis of RNA-seq data showed that 92 PK and 19 PP
      genes were not detected in roots (zero reads in three biological repeats); 96 PK
      and 10 PP showed low abundance (<= 10 reads). Gene ontology analysis revealed
      that the 188 PK genes with no or low expression level in Arabidopsis roots are
      mainly involved in pollen recognition, pollen tube growth or other processes not
      relevant for root hair formation. More than 50% of the cysteine-rich RLK
      (receptor-like protein kinase) subfamily genes belong to this group. Among the 29
      PP genes with no or low expression level, purple acid phosphatases, haloacid
      dehalogenase-like hydrolases, and PP2C genes with functions in the
      dephosphorylation of RNA polymerase II C-terminal domain and mRNA capping were
      enriched. Subsets of 173 PK and 35 PP genes were differentially expressed under
      Pi-deficient conditions. Putative functional modules (clusters) of these PK and
      PP genes were constructed based on co-expression analysis using the MACCU
      toolbox. A co-expression network comprising 65 known or annotated PK and PP genes
      (60 PK and 5 PP genes, respectively) was subdivided into several highly co
      expressed gene sub-clusters. The largest sub-cluster was composed of 22 genes,
      most of which have been assigned to the RLK superfamily and were associated with
      cell wall metabolism, pollen tube and/or root hair development and growth.
      CONCLUSIONS: We here provide comprehensive 'digital' transcriptional information
      on PK and PP genes in Arabidopsis roots. The co-expression network derived from
      our data mining approach sets the stage for follow-up experimentation that helps
      to complete our understanding of the post-translational regulation of Pi
      deficiency-induced changes in root hair morphogenesis.

PMID- 23547784
TI  - Clinical presentation, auscultation recordings, ultrasonographic findings and
      treatment response of 12 adult cattle with chronic suppurative pneumonia: case
      study.
AB  - Auscultation is considered the critical component of the veterinary clinical
      examination for the diagnosis of bovine respiratory disease but the accuracy with
      which adventitious sounds reflect underlying lung pathology remains largely
      unproven. Modern portable ultrasound machines provide the veterinary practitioner
      with an inexpensive, non-invasive tool with which to examine the pleural surfaces
      and superficial lung parenchyma. Simultaneous recording of sounds overlying
      normal lung and defined pathology allows critical assessment of auscultated
      sounds in the same animal removing confounding factors such as respiratory rate
      and thickness of the chest wall (body condition). Twelve cows, referred to the
      University of Edinburgh Veterinary School, were diagnosed with chronic
      suppurative pneumonia and enrolled into this prospective study to record and
      monitor lung sounds, ultrasonographic findings, and response to a standardised
      antibiotic treatment regimen.Most cows (8/12) had a normal rectal temperature on
      presentation but all cows had received antibiotic therapy at some time in the
      previous two weeks and six animals were receiving antibiotic treatment upon
      admission. All cattle were tachypnoeic (>40 breaths per minute) with frequent and
      productive coughing, halitosis, and a purulent nasal discharge most noticeable
      when the head was lowered. Ultrasonographic examination of the chest readily
      identified pathological changes consistent with severe lung pathology
      subsequently confirmed as chronic suppurative pneumonia in four cows at necropsy;
      eight cows recovered well after antibiotic treatment and were discharged two to
      six weeks after admission. It proved difficult to differentiate increased
      audibility of normal lung sounds due to tachypnoea from wheezes; coarse crackles
      were not commonly heard. In general, sounds were reduced in volume over
      consolidated lung relative to normal lung tissue situated dorsally. Rumen
      contraction sounds were commonly transmitted over areas of lung
      pathology.Trueperella (formerly Arcanobacterium) pyogenes was isolated from three
      of four lung tissue samples at necrospy. Treatment with procaine penicillin for
      42 consecutive days resulted in marked improvement with return to normal appetite
      and improvement in body condition in 8 of 12 cows (67%) where lesions did not
      extend more than 10-15 cm above the level of the olecranon on both sides of the
      chest.

PMID- 23547785
TI  - Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9
      (MMP-9): the next decade.
AB  - Research on matrix metalloproteinases (MMPs) and in particular on gelatinase B,
      alias MMP-9, has grown exponentially in the decade 2003-2012. Structural details
      about flexibility of MMP-9 monomers, together with glycosylation,
      oligomerization, heterogeneity and instability of the wildtype enzyme explain why
      crystallography experiments have not yet been successful for the intact enzyme.
      MMP-9 may be viewed as a multidomain enzyme in which the hemopexin, the O
      glycosylated and the catalytic domains yield support for attachment, articulation
      and catalysis, respectively. The stepwise proteolytic activation of the inactive
      zymogen into a catalytically active form becomes gradually better understood.
      Priming of activation by MMP-3 may be executed by meprins that destabilize the
      interaction of the aminoterminus with the third fibronectin repeat.
      Alternatively, autocatalytic activation may occur in the presence of molecules
      that tightly bind to the catalytic site and that push the cystein residue in the
      prodomain away from the catalytic zinc ion. Thanks to the development of
      degradomics technologies, substrate repertoires of MMP-9 have been defined, but
      it remains a challenge to determine and prove which substrates are biologically
      relevant. The substrate repertoire has been enlarged from extracellular to
      membrane-bound and efficient intracellular substrates, such as crystallins,
      tubulins and actins. Biological studies of MMP-9 have tuned the field from being
      primarily cancer-oriented towards vascular and inflammatory research. In tumor
      biology, it has been increasingly appreciated that MMP-9 from inflammatory cells,
      particularly neutrophils, co-determines prognosis and outcome. Aside from the
      catalytic functions executed by aminoterminal domains of MMP-9, the
      carboxyterminal hemopexin (PEX) domain of gelatinase B exerts non-catalytic anti
      apoptotic signaling effects. The recognition that gelatinase B is induced by many
      pro-inflammatory cytokines, whereas its inhibitors are increased by anti
      inflammatory cytokines, has generated interest to target MMP-9 in acute lethal
      conditions, such as bacterial meningitis, sepsis and endotoxin shock, and in
      acute exacerbations of chronic diseases. Previously described transcriptional
      regulation of MMP-9 is complemented by epigenetic checkpoints, including histone
      modifications and microRNAs. Because activation of proMMP-9 may be executed by
      other MMPs, the therapeutic dogma that MMP inhibitors need to be highly selective
      may be keyed down for the treatment of life-threatening conditions. When
      inflammation and MMP-9 fulfill beneficial functions to clear damaging protein
      complexes, such as in systemic autoimmune diseases, therapeutic MMP inhibition
      has to be avoided. In Mmp9 gene knockout mice, specific spontaneous phenotypes
      emerged with effects on the skeletal, reproductive and nervous systems. These
      findings not only have clinical correlates in bone growth and fertility, but also
      stimulate research on the roles of MMPs and MMP-9 in endocrinology, immunology
      and the neurosciences. Mmp9-deficient mice are valuable tools to define MMP-9
      substrates in vivo and to study the role of this enzyme in animal models of
      inflammatory, vascular, neoplastic and degenerative diseases. Future challenges
      include solving the crystal structure, definition of the functions of covalent
      oligomers and heteromers in biology and pathology, life-imaging of MMP-9
      activity, substrate determination in situ and the study of inhibitor effects on
      fertility, cancer and inflammation and in neurobiology and regenerative medicine.
      Such studies will better define conditions in which inhibition of MMP-9 is
      beneficial or has to be avoided.

PMID- 23547786
TI  - Bacteria-adsorbed palygorskite stabilizes the quaternary phosphonium salt with
      specific-targeting capability, long-term antibacterial activity, and lower
      cytotoxicity.
AB  - In order to extend the antibacterial time of quaternary phosphonium salt in
      bacteria, palygorskite (PGS) is used as the carrier of dodecyl triphenyl
      phosphonium bromide (DTP), and a DTP-PGS hybrid is prepared. Antibacterial
      performance of this novel hybrid is investigated for both Gram-positive and Gram
      negative bacteria. The results show that the DTP could be absorbed on the surface
      of PGS which had bacteria-adsorbed capability. The DTP-PGS hybrid, combining the
      advantages of PGS and DTP, display specific-targeting capability, long-term
      antibacterial activity, and lower cytotoxicity, suggesting the great potential
      application as PGS-based antibacterial powder.

PMID- 23547787
TI  - Fixating picture boundaries does not eliminate boundary extension: implications
      for scene representation.
AB  - Observers frequently remember seeing more of a scene than was shown (boundary
      extension). Does this reflect a lack of eye fixations to the boundary region?
      Single-object photographs were presented for 14-15 s each. Main objects were
      either whole or slightly cropped by one boundary, creating a salient marker of
      boundary placement. All participants expected a memory test, but only half were
      informed that boundary memory would be tested. Participants in both conditions
      made multiple fixations to the boundary region and the cropped region during
      study. Demonstrating the importance of these regions, test-informed participants
      fixated them sooner, longer, and more frequently. Boundary ratings (Experiment 1)
      and border adjustment tasks (Experiments 2-4) revealed boundary extension in both
      conditions. The error was reduced, but not eliminated, in the test-informed
      condition. Surprisingly, test knowledge and multiple fixations to the salient
      cropped region, during study and at test, were insufficient to overcome boundary
      extension on the cropped side. Results are discussed within a traditional visual
      centric framework versus a multisource model of scene perception. 

PMID- 23547788
TI  - Efficacy and safety of Elaeis guineensis and Ficus deltoidea leaf extracts in
      adults with pre-diabetes.
AB  - BACKGROUND: Individuals with pre-diabetes (fasting glucose 100-125 mg/dl) are at
      increased risk of developing diabetes; 50% of U.S. adults aged >=65 y had pre
      diabetes in 2005-08. Extracts of the leaves of E. guineensis (a tropical plant
      producing edible oil), and F. deltoidea (a traditional tea) contain phenolic
      compounds that have hypoglycemic effects in vitro and in vivo. Therefore, a study
      of the efficacy and safety of these leaf extracts was undertaken. METHODS:
      Otherwise healthy adults with pre-diabetes (15m/15f; aged 21 to 65 y; BMI >=25
      and < 40 kg/m2) were assigned to one of 3 groups for 8 weeks: E. guineensis leaf
      extract 500 mg or 1000 mg or F. deltoidea leaf extract 1000 mg. Assessments at
      baseline and throughout the study included: fasting plasma glucose, insulin,
      OGTT, and HOMA-IR; body weight and waist circumference; vital signs,
      comprehensive metabolic and lipid panels. Statistical analyses included paired
      Student's t-test and ANCOVA or non-parametric tests when indicated. RESULTS: E.
      guineensis intervention for 8 weeks decreased fasting plasma glucose and insulin
      levels, glucose and insulin areas under the curve, and insulin resistance, and
      increased insulin sensitivity. The 500 mg dose of E. guineensis had a more
      consistent effect on reducing glycemia than the 1000 mg dose and the insulin
      findings at the two dose levels were somewhat inconsistent. Differences in the
      distribution of baseline insulin levels in the low and high dose groups may
      explain some of these observed differences in responses. F. deltoidea leaf
      extract had no effect on glycemia variables but both total and LDL cholesterol
      concentrations were significantly decreased in this group. There were no
      significant differences in change of weight; however waist circumference was
      significantly lower in the E. guineensis groups after intervention. At baseline
      and after 8 weeks of intervention, vital signs and safety lab tests were within
      normal limits and not significantly different between groups or due to
      intervention. CONCLUSIONS: These results suggest that the leaf extracts of E.
      guineensis and F. deltoidea may have positive effects on glucose and lipid levels
      and are safe for use in humans. Further study is required to determine the
      maximum effective dosages and the mechanisms of action.

PMID- 23547789
TI  - Multiple ileal perforations due to regular diclofenac sodium injections: a case
      report.
AB  - BACKGROUND: Although the adverse effects of non-steroidal anti-inflammatory drugs
      (NSAIDs) on the upper gastrointestinal tract have been well characterized, those
      specific to the lower gastrointestinal tract are less clear, as only a limited
      number of articles and case reports exist in the literature. CASE PRESENTATION:
      We describe a case of a 69-year-old woman who presented to the emergency
      department due to sudden onset abdominal distension and pain. Notably, she
      reported using intramuscular diclofenac sodium twice daily for 14 days after knee
      joint replacement surgery. The patient denied any other coexisting diseases. As a
      subsequent X-ray and computed tomography (CT) scan showed free air in the
      abdomen, an exploratory laparotomy was performed, revealing four free
      perforations in the terminal ileum. Findings on microscopic analysis were non
      specific. CONCLUSION: We report a unique case of multiple ileal perforations due
      to regular diclofenac sodium injections and contend that ileal perforation can be
      considered as a source for pneumoperitoneum with concomitant peritonitis in
      patients with a history of NSAID use if other possibilities are excluded.

PMID- 23547791
TI  - Wide-field multispectral super-resolution imaging using spin-dependent
      fluorescence in nanodiamonds.
AB  - Recent advances in fluorescence microscopy have enabled spatial resolution below
      the diffraction limit by localizing multiple temporally or spectrally
      distinguishable fluorophores. Here, we introduce a super-resolution technique
      that deterministically controls the brightness of uniquely addressable,
      photostable emitters. We modulate the fluorescence brightness of negatively
      charged nitrogen-vacancy (NV(-)) centers in nanodiamonds through magnetic
      resonance techniques. Using a CCD camera, this "deterministic emitter switch
      microscopy" (DESM) technique enables super-resolution imaging with localization
      down to 12 nm across a 35 * 35 MUm(2) area. DESM is particularly well suited for
      biological applications such as multispectral particle tracking since fluorescent
      nanodiamonds are not only cytocompatible but also nonbleaching and bright. We
      observe fluorescence count rates exceeding 1.5 * 10(6) photons per second from
      single NV(-) centers at saturation. When combined with emerging NV(-)-based
      techniques for sensing magnetic and electric fields, DESM opens the door to
      rapid, super-resolution imaging for tracking and sensing applications in the life
      and physical sciences.

PMID- 23547790
TI  - Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients
      with severe sepsis and septic shock.
AB  - BACKGROUND: Procalcitonin (PCT)-protocols to guide antibiotic treatment in severe
      infections are known to be effective. But less is known about the long-term
      effects of such protocols on antibiotic consumption under real life conditions.
      This retrospective study analyses the effects on antibiotic use in patients with
      severe sepsis and septic shock after implementation of a PCT-protocol. METHODS:
      We conducted a retrospective ICU-database search for adult patients between 2005
      and 2009 with sepsis and organ dysfunction who where treated accordingly to a PCT
      guided algorithm as follows: Daily measurements of PCT (BRAHMS PCT LIA((r));
      BRAHMS Aktiengesellschaft, Hennigsdorf, Germany). Antibiotic therapy was
      discontinued if 1) clinical signs and symptoms of infection improved and PCT
      decreased to <=1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to
      25-35% of the initial value within three days. The primary outcome parameters
      were: antibiotic days on ICU, ICU re-infection rate, 28-day mortality rate,
      length of stay (LOS) in ICU, mean antibiotic costs (per patient) and ventilation
      hours. Data from 141 patients were included in our study. Primary outcome
      parameters were analysed using covariance analyses (ANCOVA) to control for
      effects by gender, age, SAPS II, APACHE II and effective cost weight. RESULTS:
      From baseline data of 2005, duration of antibiotic therapy was reduced by an
      average of 1.0 day per year from 14.3 +/-1.2 to 9.0 +/-1.7 days in 2009 (p=0.02).
      ICU re-infection rate was decreased by yearly 35.1% (95% CI -53 to -8.5; p=0.014)
      just as ventilation hours by 42 hours per year (95% CI -72.6 to -11.4; p=0.008).
      ICU-LOS was reduced by 2.7 days per year (p<0.001). Trends towards an average
      yearly reduction of 28-day mortality by -22.4% (95% CI -44.3 to 8.1; p=0.133) and
      mean cost for antibiotic therapy/ patient by -14.3 Euro (95% CI -55.7 to 27.1)
      did not reach statistical significance. CONCLUSIONS: In a real-life clinical
      setting, implementation of a PCT-protocol was associated with a reduced duration
      of antibiotic therapy in septic ICU patients without compromising clinical or
      economical outcomes. GERMAN CLINICAL TRIALS REGISTER: DRKS00003490.

PMID- 23547792
TI  - Contact angle and indentation velocity dependency for a resonance sensor-
      evaluation on soft tissue silicone models.
AB  - Human tissue stiffness can vary due to different tissue conditions such as cancer
      tumours. Earlier studies show that stiffness may be detected with a resonance
      sensor that measures frequency shift and contact force at application. Through
      the frequency shift and the contact force, a tissue stiffness parameter can be
      derived. This study evaluated how the probe application angle and indentation
      velocity affected the results and determined the maximum parameter errors. The
      evaluation was made on flat silicone discs with specified hardness. The frequency
      shift, the force and the stiffness parameter all varied with contact angle and
      indentation velocity. A contact angle of <=10 degrees  was acceptable for
      reliable measurements. A low indentation velocity was recommended. The maximum
      errors for the system were <1.1% of the measured values. It was concluded that
      contact angle and indentation velocity have to be considered in the clinical
      setting. The angular dependency is especially important in clinical use for
      studying stiffness of human soft tissue, e.g. in prostate cancer diagnosis.

PMID- 23547793
TI  - Microfabricated sampling probes for in vivo monitoring of neurotransmitters.
AB  - Microfabricated fluidic systems have emerged as a powerful approach for chemical
      analysis. Relatively unexplored is the use of microfabrication to create sampling
      probes. We have developed a sampling probe microfabricated in Si by bulk
      micromachining and lithography. The probe is 70 MUm wide by 85 MUm thick by 11 mm
      long and incorporates two buried channels that are 20 MUm in diameter. The tip of
      the probe has two 20 MUm holes where fluid is ejected or collected for sampling.
      Utility of the probe was demonstrated by sampling from the brain of live rats.
      For sampling, artificial cerebral spinal fluid was infused in through one channel
      at 50 nL/min while sample was withdrawn at the same flow rate from the other
      channel. Analysis of resulting fractions collected every 20 min from the striatum
      of rats by liquid chromatography with mass spectrometry demonstrated reliable
      detection of 17 neurotransmitters and metabolites. The small probe dimensions
      suggest it is less perturbing to tissue and can be used to sample smaller brain
      nuclei than larger sampling devices, such as microdialysis probes. This sampling
      probe may have other applications such as sampling from cells in culture. The use
      of microfabrication may also enable incorporation of electrodes for
      electrochemical or electrophysiological recording and other channels that enable
      more complex sample preparation on the device.

PMID- 23547794
TI  - Discovery of the first C-nucleoside HCV polymerase inhibitor (GS-6620) with
      demonstrated antiviral response in HCV infected patients.
AB  - Hepatitis C virus (HCV) infection presents an unmet medical need requiring more
      effective treatment options. Nucleoside inhibitors (NI) of HCV polymerase (NS5B)
      have demonstrated pan-genotypic activity and durable antiviral response in the
      clinic, and they are likely to become a key component of future treatment
      regimens. NI candidates that have entered clinical development thus far have all
      been N-nucleoside derivatives. Herein, we report the discovery of a C-nucleoside
      class of NS5B inhibitors. Exploration of adenosine analogs in this class
      identified 1'-cyano-2'-C-methyl 4-aza-7,9-dideaza adenosine as a potent and
      selective inhibitor of NS5B. A monophosphate prodrug approach afforded a series
      of compounds showing submicromolar activity in HCV replicon assays. Further
      pharmacokinetic optimization for sufficient oral absorption and liver
      triphosphate loading led to identification of a clinical development candidate GS
      6620. In a phase I clinical study, the potential for potent activity was
      demonstrated but with high intra- and interpatient pharmacokinetic and
      pharmacodynamic variability. 

PMID- 23547795
TI  - A unique small molecule inhibitor of enolase clarifies its role in fundamental
      biological processes.
AB  - Enolase is a component of the glycolysis pathway and a "moonlighting" protein,
      with important roles in diverse cellular processes that are not related to its
      function in glycolysis. However, small molecule tools to probe enolase function
      have been restricted to crystallography or enzymology. In this study, we report
      the discovery of the small molecule "ENOblock", which is the first, nonsubstrate
      analogue that directly binds to enolase and inhibits its activity. ENOblock was
      isolated by small molecule screening in a cancer cell assay to detect cytotoxic
      agents that function in hypoxic conditions, which has previously been shown to
      induce drug resistance. Further analysis revealed that ENOblock can inhibit
      cancer cell metastasis in vivo. Moreover, an unexpected role for enolase in
      glucose homeostasis was revealed by in vivo analysis. Thus, ENOblock is the first
      reported enolase inhibitor that is suitable for biological assays. This new
      chemical tool may also be suitable for further study as a cancer and diabetes
      drug candidate. 

PMID- 23547796
TI  - Fournier's gangrene: our experience with 50 patients and analysis of factors
      affecting mortality.
AB  - INTRODUCTION: Fournier's gangrene is a rare, rapidly progressive, necrotizing
      fasciitis of the external genitalia and perineum. Case series have shown a
      mortality rate of 20% to 40% with an incidence of as high as 88% in some reports.
      In this study we aimed to share our experience in the management of Fournier's
      gangrene and to identify risk factors that affect mortality. METHODS: The medical
      records of 50 patients with Fournier's gangrene who presented at the University
      Hospital Hassan II of Fez from January 2003 to December 2009 were reviewed
      retrospectively to analyze the outcome and identify the risk factors and
      prognostic indicators of mortality. RESULTS: Ten males and five females were
      enrolled in the study. The mean age was 54 years (range 23-81). The most common
      predisposing factor was diabetes mellitus (34%). E. coli was the most frequent
      bacterial organisms cultured. All patients were treated with a common approach of
      resuscitation, broad-spectrum antibiotics, and wide surgical excision. The
      mortality rate was 24%. The advanced age, renal failure on admission, extension
      of infection to the abdominal wall, occurrence of septic shock and need for
      postoperative mechanical ventilation are the main prognostic factors of
      mortality. In multivariate analysis, none of these variables is an independent
      predictor of mortality. CONCLUSIONS: Fournier's gangrene is still a very severe
      disease with high mortality rates. Early recognition of infection associated with
      invasive and aggressive treatment is essential for attempting to reduce these
      prognostic indices.

PMID- 23547797
TI  - Neonatal mortality in Sudan: analysis of the Sudan household survey, 2010.
AB  - BACKGROUND: Sudan is classified as having insufficient progress in achieving the
      Millennium Development Goal (MDG-4), where the levels of child and infant
      mortality are among the highest in the region and the world. This study
      investigated factors associated with neonatal mortality in Sudan. Neonatal death
      is defined as death within the first 28 days of life. METHODS: This study
      analysed data from the Sudan Household Health Survey 2nd round, which was carried
      out in 2010. Total of 6,198 live-born infants delivered within the two years
      preceding the survey were included as the study population. Multivariate logistic
      regression was used to model neonatal mortality as a function of maternal health
      parameters, socioeconomic indicators and the sex of the child. RESULTS: There
      were 189 neonatal deaths out of 6,198 live births (3.0%). In the multiple
      logistic regression, the factors associated with neonatal mortality were advanced
      maternal age (>= 40 years; OR = 2.4; 95% CI: 1.21, 4.78, p = 0.012), poor
      household wealth index (OR = 1.6; 95% CI: 1.18, 2.47, p = 0.005), male child (OR
      = 1.8; 95% CI: 1.31, 2.42, p < 0.001), delivery of baby by Caesarean section (OR
      = 1.6; 95% CI: 1.78, 2.42, p = 0.013) and delivery complications (OR = 1.4; 95%
      CI: 1.18, 2.15, p = 0.002). CONCLUSION: Public health interventions which target
      neonatal mortality reduction should adopt a risk-factor-based approach to detect
      pregnancy complications early and once identified, the health system should be
      strengthened so that these complications can be dealt with adequately.

PMID- 23547798
TI  - Antioxidant and metabolite profiling of North American and neotropical
      blueberries using LC-TOF-MS and multivariate analyses.
AB  - There are many neotropical blueberries, and recent studies have shown that some
      have even stronger antioxidant activity than the well-known edible North American
      blueberries. Antioxidant marker compounds were predicted by applying multivariate
      statistics to data from LC-TOF-MS analysis and antioxidant assays of 3 North
      American blueberry species (Vaccinium corymbosum, Vaccinium angustifolium, and a
      defined mixture of Vaccinium virgatum with V. corymbosum) and 12 neotropical
      blueberry species (Anthopterus wardii, Cavendishia grandifolia, Cavendishia
      isernii, Ceratostema silvicola, Disterigma rimbachii, Macleania coccoloboides,
      Macleania cordifolia, Macleania rupestris, Satyria boliviana, Sphyrospermum
      buxifolium, Sphyrospermum cordifolium, and Sphyrospermum ellipticum). Fourteen
      antioxidant markers were detected, and 12 of these, including 7 anthocyanins, 3
      flavonols, 1 hydroxycinnamic acid, and 1 iridoid glycoside, were identified. This
      application of multivariate analysis to bioactivity and mass data can be used for
      identification of pharmacologically active natural products and may help to
      determine which neotropical blueberry species will be prioritized for
      agricultural development. Also, the compositional differences between North
      American and neotropical blueberries were determined by chemometric analysis, and
      44 marker compounds including 16 anthocyanins, 15 flavonoids, 7 hydroxycinnamic
      acid derivatives, 5 triterpene glycosides, and 1 iridoid glycoside were
      identified.

PMID- 23547799
TI  - Genome sequencing of bacteria: sequencing, de novo assembly and rapid analysis
      using open source tools.
AB  - BACKGROUND: De novo genome sequencing of previously uncharacterized
      microorganisms has the potential to open up new frontiers in microbial genomics
      by providing insight into both functional capabilities and biodiversity. Until
      recently, Roche 454 pyrosequencing was the NGS method of choice for de novo
      assembly because it generates hundreds of thousands of long reads (<450 bps),
      which are presumed to aid in the analysis of uncharacterized genomes. The array
      of tools for processing NGS data are increasingly free and open source and are
      often adopted for both their high quality and role in promoting academic freedom.
      RESULTS: The error rate of pyrosequencing the Alcanivorax borkumensis genome was
      such that thousands of insertions and deletions were artificially introduced into
      the finished genome. Despite a high coverage (~30 fold), it did not allow the
      reference genome to be fully mapped. Reads from regions with errors had low
      quality, low coverage, or were missing. The main defect of the reference mapping
      was the introduction of artificial indels into contigs through lower than 100%
      consensus and distracting gene calling due to artificial stop codons. No
      assembler was able to perform de novo assembly comparable to reference mapping.
      Automated annotation tools performed similarly on reference mapped and de novo
      draft genomes, and annotated most CDSs in the de novo assembled draft genomes.
      CONCLUSIONS: Free and open source software (FOSS) tools for assembly and
      annotation of NGS data are being developed rapidly to provide accurate results
      with less computational effort. Usability is not high priority and these tools
      currently do not allow the data to be processed without manual intervention.
      Despite this, genome assemblers now readily assemble medium short reads into long
      contigs (>97-98% genome coverage). A notable gap in pyrosequencing technology is
      the quality of base pair calling and conflicting base pairs between single reads
      at the same nucleotide position. Regardless, using draft whole genomes that are
      not finished and remain fragmented into tens of contigs allows one to
      characterize unknown bacteria with modest effort.

PMID- 23547800
TI  - Recent advances in proteasome inhibitor discovery.
AB  - INTRODUCTION: Proteasome inhibition is a quickly advancing subject of research
      and has a significant potential to become a potent therapeutic modality for many
      diseases and disorders. The aim of this review is to present the reader with the
      variety of approaches to the proteasome inhibitor discovery as well as highlight
      the diversity of scaffolds being considered for this task. AREAS COVERED: This
      review focuses on current developments in proteasome inhibitor discovery,
      including an account of research efforts covered in the literature from the years
      2009 - 2012, although some of the earlier work is also mentioned. Specifically,
      presented are the type of experiments performed, the compounds and compound
      families investigated along with their activities and assessment for potential
      therapeutic value. In particular, authors highlight different paths to discovery
      of the proteasome inhibitors such as screening of large libraries, repurposing of
      existing therapeutics, development of compounds with known proteasome inhibitory
      activities as well as utilizing novel scaffolds. EXPERT OPINION: Discovery of
      therapeutically successful proteasome inhibitors depends on a number of factors
      and demands a multipronged approach. Screening protocols, choice of assays,
      desired mode of action, selection of a binding pocket, targeting and delivery
      strategy, all require careful consideration when attempting to target the
      proteasome.

PMID- 23547801
TI  - Molecular mechanism of monodisperse colloidal tin-doped indium oxide nanocrystals
      by a hot-injection approach.
AB  - Molecular mechanisms and precursor conversion pathways associated with the
      reactions that generate colloidal nanocrystals are crucial for the development of
      rational synthetic protocols. In this study, Fourier transform infrared
      spectroscopy technique was employed to explore the molecular mechanism associated
      with the formation of tin-doped indium oxide (ITO) nanocrystals. We found that
      the reaction pathways of the indium precursor were not consistent with simple
      ligand replacements proposed in the literature. The resulting understanding
      inspired us to design a hot-injection approach to separate the ligand
      replacements of indium acetate and the aminolysis processes, generating quality
      ITO nanocrystals with decent size distributions. The hot-injection approach was
      readily applied to the synthesis of ITO nanocrystals with a broad range of tin
      doping. Structural, chemical, and optical analyses revealed effective doping of
      Sn4+ ions into the host lattices, leading to characteristic and tunable near
      infrared surface plasmon resonance peaks. The size control of ITO nanocrystals by
      multiple hot-injections of metal precursors was also demonstrated.

PMID- 23547802
TI  - Interpreting ion-specific effects on the reduction of an arenediazonium ion by t
      butylhydroquinone (TBHQ) using the pseudophase kinetic model in emulsions
      prepared with a zwitterionic sulfobetaine surfactant.
AB  - Specific salt effects on the reduction of an amphiphilic arenediazonium ion, 16
      ArN2(+), by TBHQ in opaque, stirred, and kinetically stable emulsions prepared
      with a zwitterionic sulfobetaine surfactant are consistent with the chameleon
      effect: selective anion binding/induced cation binding in the interfacial region
      of the emulsions. Added NaX salts with different anions decrease the observed
      first-order rate constant, k(obs), for the reduction in the order X(-) = ClO4(-)
      > Br(-) ~ CCl3CO2(-) > Cl(-) > MeSO3(-). Added MCln salts of increasing cation
      valence at constant total Cl(-) concentration increase kobs in the order M(n+) =
      Cs(+) < Ca(2+) < Al(3+) in the same emulsions. These results, combined with
      recent results for nonionic and ionic emulsions, demonstrate that pseudophase
      kinetic models provide general, coherent explanations of chemical reactivity in
      homogeneous micelles, microemulsions, vesicles, and now biphasic emulsions and
      with all types of basic surfactant structures: nonionic, cationic, anionic, and
      now zwitterionic.

PMID- 23547803
TI  - Mutuality and the social regulation of neural threat responding.
AB  - Recent studies have shown that the presence of a caring relational partner can
      attenuate neural responses to threat. Here we report reanalyzed data from Coan,
      Schaefer, and Davidson ( 2006 ), investigating the role of relational mutuality
      in the neural response to threat. Mutuality reflects the degree to which couple
      members show mutual interest in the sharing of internal feelings, thoughts,
      aspirations, and joys - a vital form of responsiveness in attachment
      relationships. We predicted that wives who were high (versus low) in perceived
      mutuality, and who attended the study session with their husbands, would show
      reduced neural threat reactivity in response to mild electric shocks. We also
      explored whether this effect would depend on physical contact (hand-holding). As
      predicted, we observed that higher mutuality scores corresponded with decreased
      neural threat responding in the right dorsolateral prefrontal cortex and
      supplementary motor cortex. These effects were independent of hand-holding
      condition. These findings suggest that higher perceived mutuality corresponds
      with decreased self-regulatory effort and attenuated preparatory motor activity
      in response to threat cues, even in the absence of direct physical contact with
      social resources.

PMID- 23547804
TI  - Osteoprotegerin and mortality in hemodialysis patients with cardiovascular
      disease.
AB  - BACKGROUND: Patients treated with hemodialysis (HD) have an increased mortality,
      mainly caused by cardiovascular disease (CVD). Osteoprotegerin (OPG) is a
      glycoprotein involved in the regulation of the vascular calcification process.
      Previous studies have demonstrated that OPG is a prognostic marker of mortality.
      The aim of this study was to investigate if OPG was a prognostic marker of all
      cause mortality in high-risk patients with end-stage renal disease and CVD.
      METHODS: We prospectively followed 206 HD patients with CVD. OPG was measured at
      baseline and the patients were followed for 2 years or until reaching the primary
      endpoint, i.e., all-cause mortality. RESULTS: All-cause mortality during follow
      up was 44% (90/206). High OPG was associated with increased mortality, using the
      first tertile as reference, with an unadjusted HR of 1.70 (CI 1.00 - 2.88) for
      the second tertile and HR of 1.63 (CI 0.96 - 2.78) for the third tertile. In a
      multivariate Cox-regression analysis age, CRP and OPG in both the second and
      third tertile were significantly associated with increased mortality In the
      unadjusted survival analysis, a test for trend of OPG yielded a p-value of 0.08;
      in the adjusted analyses, the p-value for trend was 0.03. CONCLUSIONS: In a high
      risk population of hemodialysis patients with previously documented
      cardiovascular disease, a high level of OPG was an independent risk marker of all
      cause mortality.

PMID- 23547805
TI  - IgG4-related disease: a case report and review of cases reported in China.
AB  - IgG4-related inflammatory pseudotumors are lesions characterized by plasma cell
      rich histologic pattern, abundant IgG4-positive plasma cells and high serum IgG4
      levels. A 64-year-old man was admitted to our hospital for an ultrasound
      documented space-occupying lesion of the left kidney. Renal tumor of the left
      kidney was suspected based upon results of computed tomography and nuclear
      magnetic resonance, and laparoscopic radical nephrectomy was conducted. The final
      diagnosis of IgG4-related inflammatory pseudotumor was made based on
      histopathological examination and IgG4 immunostaining. The patient received
      steroid therapy. To our knowledge, this is the first case of IgG4-related
      inflammatory pseudotumor of the kidney reported in China. 

PMID- 23547806
TI  - The associations between serum paraoxonase 1 activity and carotid atherosclerosis
      in renal transplant patients.
AB  - BACKGROUNDS AND AIMS: Paraoxonase 1 (PON1) is a novel marker that has been shown
      to exert protective functions on atherosclerosis by preventing oxidative
      modification of serum lipoproteins. In this study, we investigated the effects of
      PON1 on CA-IMT in renal transplant patients. METHODS: A total of 98 adult renal
      transplant recipients was enrolled in the study. CA-IMT was determined by B-mode
      Doppler ultrasonography. PON-1 activity was assessed by the rate of enzymatic
      hydrolysis of paraoxon to p-nitrophenol. RESULTS: Mean age was 39.4 +/- 9.6 years
      and 10% of the patients were diabetic. Time after transplant was 76 +/- 59
      months. Mean PON1 level was 62.1 +/- 43.3 U/l. PON1 levels were negatively
      correlated with CA-IMT and positively with HDL cholesterol. Mean CA-IMT was 0.62
      +/- 0.10 mm (0.40 - 0.98). CA-IMT was positively correlated with age, male gender
      and negatively with proteinuria and PON1 levels. In linear regression analysis,
      PON1 levels were associated with CA-IMT. CONCLUSION: Reduced PON1 activity is
      significantly associated with increased carotid atherosclerosis in renal
      transplant patients.

PMID- 23547807
TI  - Co-incident BK and Epstein-Barr virus replication in a 3-year-old immunocompetent
      boy.
AB  - We present a unique case of infectious mononucleosis attended with transient
      asymptomatic BK virus (BKV) manifestation in the urine of an immunocompetent
      caucasian boy without kidney dysfunction. The urine sediment showed abundant
      decoy cells initially misdiagnosed as malignant cancer cells. This case
      demonstrates that the occurrence of polyoma-BKV bearing decoy cells is self
      limiting and not necessarily associated with overt kidney disease in an
      immunocompetent child. The shedding of decoy cells into the urine might be
      promoted by viral co-infections modulating the host's immune response such as
      infectious mononucleosis.

PMID- 23547808
TI  - Human sirtuins: an overview of an emerging drug target in age-related diseases
      and cancer.
AB  - Sir2-like proteins (Sirtuins) are a class of enzymes conserved throughout the
      kingdoms of life. In fact, from Archaea to Mammals, these (class III) NAD+
      dependent deacetylases catalyse the removal of the acetyl moiety from a substrate
      protein. Sirtuins show a conserved central catalytic domain with two more
      variable amino- and carboxy-terminal flanking regions. Amino acid comparison of
      these central conserved catalytic core sequences allows us to divide Sirtuins
      into five different classes (I, II, III, IV and U). These proteins differ in
      their subcellular localization (i.e. in Eukaryotes they can be found in the
      nucleus, cytoplasm or mitochondria). In humans there are seven Sirtuins (SIRT1-7)
      that are implicated in various physiological processes including aging and age
      related disorders such as neoplasms, cardiovascular, metabolic and
      neurodegenerative diseases, and inflammation. Nowadays, the estimated life
      expectancy is definitely longer than in the past thus, we may consider all aging
      related problems as having a strong social impact. Consequently, Sirtuins are
      emerging, particularly from a pharmacological point of view, as new and valuable
      drug targets.

PMID- 23547809
TI  - Sirtuin-1 and HIV-1: an overview.
AB  - Sirtuins are a family of NAD+-dependent protein deacetylases, which regulate cell
      survival and energy metabolism, inflammation and cancer. Recent studies have
      shown that sirtuin-1 (SIRT1) modulates Human Immunodeficiency Virus (HIV)-1
      transcription. The HIV-1 Tat protein is a substrate for the deacetylase activity
      of SIRT1; SIRT1 recycles Tat to its unacetylated form, catalyzing a fundamental
      step to start new cycles of viral transcription. Moreover, Tat has been reported
      to promote T-cell hyperactivation by suppressing SIRT1 activity. In fact, Tat
      blocks the ability of SIRT1 to deacetylate lysine 310 in the p65 subunit of
      nuclear factor- kappaB (NF- kappaB) by interacting with the deacetylase domain of
      SIRT1. This mechanism leads therefore to the hyperactivation of NF- kappaB
      proinflammatory pathway and may likely contribute to the chronic immune
      activation state of HIV-infected individuals. In the present review we first
      briefly describe the biological functions of sirtuins, then we delineate the
      interplay between SIRT1 and HIV-1 and discuss the potential role of SIRT1 as a
      pharmacological target of HIV-1 replication.

PMID- 23547810
TI  - Serotonin (5-HT) in the regulation of depression-related emotionality: insight
      from 5-HT transporter and tryptophan hydroxylase-2 knockout mouse models.
AB  - Disorders of emotion regulation such as anxiety disorders and depression are
      common and yet debilitating. Accumulating evidence suggests involvement of
      serotonin (5-HT) in the regulation of emotion. Mice with targeted deletion of
      genes encoding mediators of the serotonergic transmission have proven to be a
      powerful tool for understanding contributions of such mediators of emotion
      regulation. Over the last decade, research on mice with a targeted inactivation
      of the 5-HT transporter (5-Htt, Sert, Slc6a4) has considerably advanced our
      knowledge about functions that the 5-HTT plays in the context of emotion related
      to depression. Moreover, the recent advent of knockout (KO) mice for tryptophan
      hydroxylase 2 (Tph2 KO), which lacks the rate-limiting enzyme for 5-HT synthesis
      in the brain, has further provided insight to the brain serotonergic system and
      its role in emotion dysregulation. Here, we first highlight basic characteristics
      of the serotonergic system including the biosynthesis of 5-HT as well as the
      anatomy and firing activity of serotonergic neurons. Furthermore, characteristics
      of 5-Htt and Tph2 KO mice are covered together with association studies on human
      variants of 5-HTT and TPH2 in emotional regulation. Among various targets of
      serotonergic projections, which originate from the raphe nuclei in the brain
      stem, particular focus is placed on the hippocampus due to its unique dual role
      in memory and emotion. Finally, effects of therapeutic drugs and psychoactive
      drugs on KO mouse models as well as on synaptic plasticity will be discussed.

PMID- 23547811
TI  - Decoding coronary artery disease: somatic mosaicism and genomics for personal and
      population risk prediction.

PMID- 23547812
TI  - Vitamin D and multiple sclerosis: timing of sampling, treatment and prevention.

PMID- 23547813
TI  - BCHE reported to be associated with plaque level in Alzheimer's disease.

PMID- 23547814
TI  - miRNA interactions as a novel molecular panel for clinical outcome of
      glioblastoma.

PMID- 23547815
TI  - Circulating miR-122 as a potential biomarker of liver disease.
AB  - AIM: Expression profiles indicate that miR-122 is specifically and abundantly
      expressed in liver. This study sought to determine miR-122 plasma concentrations
      in 15 apparently healthy subjects and 30 patients with liver disease, and clarify
      whether plasma miR-122 correlates with ALT. MATERIALS & METHODS: miR-122 was
      measured by quantitative PCR in healthy volunteers and patients with liver
      disease. RESULTS: ALT was increased in two out of 15 (13%) apparently healthy
      subjects and 17 out of 30 (57%) liver disease patients. In healthy subjects,
      median miR-122 plasma concentration was 51.7 copies/20 pg RNA (range 16.0-312.0).
      In liver disease patients, median miR-122 was significantly elevated to 202.3
      copies/20 pg RNA (range 20.9-1160.0; Mann-Whitney test between median
      concentrations; p = 0.0016). CONCLUSION: This small proof-of-principle study
      suggests that miR-122 may be a potential plasma biomarker of liver damage.

PMID- 23547816
TI  - The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen
      biomarkers in chronic obstructive pulmonary disease patients.
AB  - AIM: The evidence on the acute effects of smoking on biomarkers is limited. Our
      aim was to study the acute effect of smoking on disease-related biomarkers.
      METHODS: The acute effect of smoking on serum high sensitivity CRP (hs-CRP) and
      plasma fibrinogen and its association with disease severity was studied by
      challenging 31 chronic obstructive pulmonary disease patients with cigarette
      smoking and repeatedly measuring these biomarkers before and after smoking.
      RESULTS: Fibrinogen and hs-CRP increased directly after smoking by 9.4 mg/dl (95%
      CI: 4.2-14.5) and 0.13 mg/l (95% CI: 0.03-0.23), respectively. Fibrinogen levels
      remained elevated after 35 min, whereas hs-CRP normalized. Pearson's correlation
      coefficient between the hs-CRP change and chronic obstructive pulmonary disease
      severity was 0.25 (p = 0.06). CONCLUSION: Fibrinogen and hs-CRP increased
      directly after smoking in the chronic obstructive pulmonary disease patients.
      Their association with disease risk and/or progression remains to be
      demonstrated.

PMID- 23547817
TI  - Diagnostic value of NT-proBNP in identifying impaired coronary flow reserve in
      asymptomatic moderate or severe aortic stenosis.
AB  - AIM: NT-proBNP has been shown to be a reliable biochemical marker for left
      ventricular wall stress. The relationship between NT-proBNP and coronary flow
      reserve (CFR) was evaluated in patients with significant asymptomatic aortic
      stenosis (AS). METHODS: A total of 74 patients with moderate or severe AS, mean
      age 66.68 +/- 10.02 years (56.75% males), were enrolled in this prospective
      study. All patients underwent coronary angiography and had no obstructive
      coronary disease (defined as having no stenosis >50% in diameter). They had all
      undergone standard transthoracic Doppler-echo study and adenosine stress
      transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP
      measurement. RESULTS: The median NT-proBNP value was significantly increased
      (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was
      significantly higher in the group with CFR <=2.5 (median: 549.0 pg/ml; IQR: 311.5
      1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452;
      p = 0.012). NT-proBNP showed significant negative correlation with CFR (rho = 
      0.377, p = 0.001). There was also significant correlation between NT-proBNP and
      E/E', S' and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was
      determined as the best cut-off value for the diagnosis of CFR <=2.5 (area under
      the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity
      were 74 and 64%, respectively. CONCLUSION: Elevated NT-proBNP can indicate
      patients with impaired CFR in asymptomatic moderate or severe AS patients with
      preserved ejection fraction and nonobstructive coronary arteries.

PMID- 23547818
TI  - Biomarkers of oxidative stress in women with pre-eclampsia.
AB  - AIM: The potential role of oxidative stress in the pathophysiology of pre
      eclampsia has been reported in the literature. There are only a few studies that
      have investigated changes in malondialdehyde (MDA), vitamin E and total blood
      glutathione together in pre-eclampsia. Therefore, the aim of this study was to
      measure the levels of MDA, vitamin E and total glutathione as putative
      circulatory markers of oxidative stress for the early detection of pre-eclampsia.
      PATIENTS & METHODS: In this case-control study, blood samples were collected from
      40 pre-eclamptic and 80 normal pregnant females at the department of obstetrics
      and gynecology at King Abdulaziz Medical City (Riyadh, Saudi Arabia) between
      February 2009 and January 2010. Circulating markers of oxidative stress were
      evaluated, including MDA, total glutathione and vitamin E, by high-performance
      liquid chromatography. RESULTS: Markers of oxidative stress including serum MDA,
      total glutathione and vitamin E were found to be significantly different in both
      groups. CONCLUSION: MDA, vitamin E and blood total glutathione are possible
      candidate markers to predict pre-eclampsia.

PMID- 23547819
TI  - The associations between high-density lipoprotein mean particle size and its
      fatty acid composition.
AB  - AIM: High-density lipoprotein (HDL) particles are heterogeneous in their
      composition, structure and size and may differ in conferring protection against
      coronary artery disease. The aim of this study is to investigate the associations
      between HDL size and its fatty acid composition. PATIENTS & METHODS: HDL mean
      particle size from 140 healthy men was detected by dynamic light scattering
      methodology and fatty acid composition of HDL was determined by gas
      chromatography. RESULTS: HDL with smaller size had a higher proportion of
      saturated fatty acids and lower proportion of unsaturated fatty acids. HDL mean
      size indicated a negative correlation with palmitic acid (r = -0.17; p < 0.05)
      and a positive correlation with palmitoleic acid (r = 0.17; p < 0.05), oleic acid
      (r = 0.23; p < 0.01), arachidonic acid (r = 0.17; p < 0.05) and
      dihomogamalinoleic acid (r = -0.18; p < 0.05). CONCLUSION: Saturated fatty acids
      of HDL are inversely assocaited and unsaturated fatty acids are directly
      associated with HDL mean size.

PMID- 23547821
TI  - Exhaled nasal nitric oxide during humming: potential clinical tool in sinonasal
      disease?
AB  - The use of nasal nitric oxide (nNO) in sinonasal disease has recently been
      advocated as a potential tool to explore upper inflammatory airway disease.
      However, it is currently hampered by some factors including the wide range of
      measurement methods, the presence of various confounding factors and the
      heterogeneity of the study population. The contribution of nasal airway and
      paranasal sinuses communicating with the nose through the ostia represents the
      main confounding factor. There is accumulating evidence that nasal humming (which
      is the production of a tone without opening the lips or forming words) during nNO
      measurement increases nNO levels due to a rapid gas exchange in the paranasal
      sinuses. The aim of this review is to discuss the basic concepts and clinical
      applications of nNO assessment during humming, which represents a simple and
      noninvasive method to approach sinonasal disease.

PMID- 23547822
TI  - Circulating biomarkers of CNS tumors: an update.
AB  - CNS tumors comprise approximately 120 histological subtypes. Advances of surgical
      resection, radiation and systemic therapy have increased the survival rates of
      distinct types of CNS tumor patients. There is growing interest in identification
      of diagnostic, prognostic or predictive blood biomarkers in CNS tumor patients,
      and emerging studies indicate that certain brain tumors are indeed associated
      with distinct profiles of circulating factors such as proteins (e.g., glial
      fibrillary acidic protein), DNA fragments (e.g., containing mutated IDH) or
      miRNAs (e.g., miRNA-21). However, blood biomarker research in neurooncology is,
      for the most part, at an exploratory level, and adequately powered and well
      designed studies are needed to translate the available interesting but
      preliminary findings into actual clinical use. In this review, the current
      knowledge on circulating biomarkers of CNS tumors is briefly summarized.

PMID- 23547820
TI  - Newborn screening for autism: in search of candidate biomarkers.
AB  - BACKGROUND: Autism spectrum disorder (ASD) represents a wide range of
      neurodevelopmental disorders characterized by impairments in social interaction,
      language, communication and range of interests. Autism is usually diagnosed in
      children 3-5 years of age using behavioral characteristics; thus, diagnosis
      shortly after birth would be beneficial for early initiation of treatment. AIM:
      This retrospective study sought to identify newborns at risk for ASD utilizing
      bloodspot specimens in an immunoassay. MATERIALS & METHODS: The present study
      utilized stored frozen specimens from ASD children already diagnosed at 15-36
      months of age. The newborn specimens and controls were analyzed by immunoassay in
      a multiplex system that included 90 serum biomarkers and subjected to statisical
      analysis. RESULTS: Three sets of five biomarkers associated with ASD were found
      that differed from control groups. The 15 candidate biomarkers were then
      discussed regarding their association with ASD. CONCLUSION: This study determined
      that a statistically selected panel of 15 biomarkers successfully discriminated
      presumptive newborns at risk for ASD from those of nonaffected controls.

PMID- 23547823
TI  - Circulating miRNAs: novel biomarkers of acute coronary syndrome?
AB  - Acute coronary syndrome refers to any group of clinical symptoms compatible with
      acute myocardial infarction (AMI). AMI is a major cause of death and disability
      worldwide with the greatest risk of death within the first hours of AMI onset.
      Therefore, delays in 'ruling in' AMI may increase morbidity and mortality due to
      the time lag in initiating therapy. Likewise, since the majority of patients
      presenting with acute chest pain do not have AMI, the rapid 'ruling out' of AMI
      in those patients would increase emergency department triage efficiency, decrease
      medical costs, and reduce morbidity and mortality. Thus, the identification of
      novel biomarkers that improve current strategies and/or accurately identify
      subjects who are at risk of developing acute and chronic manifestations of
      cardiovascular disease are desperately needed. This article discusses the
      potential of peripheral blood microRNAs as clinical biomarkers for the diagnosis
      and prognosis of cardiovascular diseases such as AMI.

PMID- 23547824
TI  - Hopes and challenges in using miRNAs as translational biomarkers for drug-induced
      liver injury.
AB  - There is a need for better biomarkers of drug-induced liver injury (DILI) to
      guide risk assessment and patient management. Over the past 3 years, both animal
      and clinical studies have provided proof-of-concept data showing that a subset of
      miRNAs appear to offer unique advantages over the conventional DILI biomarkers,
      such as enhanced sensitivity and specificity, reduced inter-individual
      variations, the potential to differentiate lethal and nonlethal liver injury, and
      the ability to reflect the patterns and even the etiology of liver injury.
      Notably, many studies have demonstrated that level of miR-122, a liver-enriched
      miRNA accounting for approximately 70% of total hepatic miRNAs, was increased
      many fold in the blood when DILI occurred. However, currently available data are
      predominantly based on animal models and not human samples. Due to the lack of a
      standard quantification method for miRNAs and confirmatory studies using a
      comprehensive list of drugs and patients, the true value of all reported miRNA
      biomarkers remains to be carefully assessed. An outstanding challenge is to
      examine if miRNAs are also useful for idiosyncratic DILI, which constitutes the
      major part of clinical DILI cases but generally cannot be recapitulated in
      traditional animal models or in clinical trials (the latter due to its relative
      rarity).

PMID- 23547825
TI  - Putting it into perspective: multimarker panels for cardiovascular disease risk
      assessment.
AB  - Cardiovascular biomarkers started as tools to aid with specific medical
      diagnoses, but are now being used broadly for screening, prognosis and monitoring
      of multiple diseases. Novel markers that reflect important pathophysiologic
      pathways are emerging regularly, although each new set of markers introduced
      raises many questions on how best to utilize them to improve patient outcomes.
      One promising approach for getting the most out of cardiovascular biomarkers is
      to combine multiple markers together into a multimarker panel. When each marker
      represents a distinct pathophysiologic pathway, the combined panel has advantages
      over individual biomarkers and may be useful when used in specific clinical
      scenarios for assessing risk, improving diagnosis or directing individualized
      therapy. This perspective article highlights several of the most promising
      biomarkers and strategies for achieving improved cardiovascular risk assessment
      for primary prevention of cardiovascular disease via multimarker panels.

PMID- 23547827
TI  - Inosine triphosphate pyrophosphohydrolase (ITPA) polymorphic sequence variants in
      adult hematological malignancy patients and possible association with
      mitochondrial DNA defects.
AB  - BACKGROUND: Inosine triphosphate pyrophosphohydrolase (ITPase) is a 'house
      cleaning' enzyme that degrades non-canonical ('rogue') nucleotides. Complete
      deficiency is fatal in knockout mice, but a mutant polymorphism resulting in low
      enzyme activity with an accumulation of ITP and other non-canonical nucleotides,
      appears benign in humans. We hypothesised that reduced ITPase activity may cause
      acquired mitochondrial DNA (mtDNA) defects. Furthermore, we investigated whether
      accumulating mtDNA defects may then be a risk factor for cell transformation, in
      adult haematological malignancy (AHM). METHODS: DNA was extracted from peripheral
      blood and bone marrow samples. Microarray-based sequencing of mtDNA was performed
      on 13 AHM patients confirmed as carrying the ITPA 94C>A mutation causing low
      ITPase activity, and 4 AHM patients with wildtype ITPA. The frequencies of ITPA
      94C>A and IVS2+21A>C polymorphisms were studied from 85 available AHM patients.
      RESULTS: ITPA 94C>A was associated with a significant increase in total
      heteroplasmic/homoplasmic mtDNA mutations (p<0.009) compared with wildtype ITPA,
      following exclusion of haplogroup variants. This suggested that low ITPase
      activity may induce mitochondrial abnormalities. Compared to the normal
      population, frequencies for the 94C>A and IVS2+21A>C mutant alleles among the AHM
      patients were higher for myelodyplastic syndrome (MDS) - but below significance;
      were approximately equivalent for chronic lymphoblastic leukemia; and were lower
      for acute myeloid leukemia. CONCLUSIONS: This study invokes a new paradigm for
      the evolution of MDS, where nucleotide imbalances produced by defects in 'house
      cleaning' genes may induce mitochondrial dysfunction, compromising cell
      integrity. It supports recent studies which point towards an important role for
      ITPase in cellular surveillance of rogue nucleotides.

PMID- 23547828
TI  - Rapid, effective and user-friendly immunophenotyping of canine lymphoma using a
      personal flow cytometer.
AB  - BACKGROUND: Widespread use of flow cytometry for immunophenotyping in clinical
      veterinary medicine is limited by cost and requirement for considerable
      laboratory space, staff time, and expertise. The Guava EasyCyte Plus (Guava
      Technologies, Hayward, CA, US) is the first, personal, bench-top flow cytometer
      designed to address these limitations. OBJECTIVE: The aim of this study was to
      adapt the immunohistochemical protocol used for immunophenotyping of canine
      lymphoma to the personal flow cytometer for rapid, effective and user-friendly
      application to the diagnosis and prognosis of canine lymphoma and to demonstrate
      its practicality for widespread veterinary application. Performance of the
      personal flow cytometer for immunophenotyping T and B lymphocytes in blood and
      lymph nodes from normal dogs and dogs with lymphoproliferative disease, was
      assessed using only two monoclonal antibodies (against CD3 and CD21), and by
      comparison with analysis using two conventional flow cytometers. METHODS: 26 dogs
      with lymphoproliferative disease (23 with lymphoma, 3 with lymphocytic leukaemia)
      were studied along with 15 controls (2 non-lymphoma lymph nodes and 13 non
      leukemic bloods. Lymphocytes were immunostained with fluorescent-labeled,
      monoclonal antibodies against CD3 and CD21. To assess the effectiveness of the
      personal flow cytometer in discrimination between T and B cell immunophenotypes,
      T and B cell counts for half the samples (14 blood and 11 lymph node) were also
      determined using the same method and conventional flow cytometers (FACSCalibur,
      Cyan Dako). To assess the effectiveness of the personal flow cytometer in
      discriminating between leukocyte types, lymphocyte differential counts were
      determined for 21 blood samples and compared with those from automated hematology
      analyzers (CELL-DYN 3500, n=11 and ADVIA 2120, n=10). Quality and sub-cellular
      distribution of immunostaining was assessed using fluorescence microscopy.
      RESULTS: The protocol for immunophenotyping took 2 to 3 hours to complete from
      the point of receipt of sample to reporting of immunophenotype. The personal flow
      cytometer differential lymphocyte counts correlated highly (n=20; r=0.97,
      p<0.0001) with those of automated haematology analyzers. The personal flow
      cytometer counts consistently, but mildly, underestimated the percentages of
      lymphocytes in the samples (mean bias of -5.3%.). The personal flow cytometer
      immunophenotype counts were indistinguishable from those of conventional flow
      cytometers for both peripheral blood samples (n=13; r=0.95; p<0.0001; bias of 
      1.1%) and lymph node aspirates (n=11,r=0.98; p<0.001; bias of 1%). All but one
      leukemic and one lymphomatous lymph node sample, out of 26 samples of dogs with
      lymphoproliferative disease analyzed, could be immunophenotyped as either B or T
      cells. CONCLUSIONS: We conclude that use of only 2 monoclonal antibodies is
      sufficient for immunophenotyping most cases of canine lymphoma by flow cytometry
      and enables rapid immunophenotyping. The personal flow cytometer may be as
      effectively used for immunophenotyping canine lymphoma as conventional flow
      cytometers. However, the personal flow cytometer is more accessible and user
      friendly, and requires lower sample volumes.

PMID- 23547829
TI  - Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease
      (NAFLD).
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease,
      which includes a spectrum of hepatic pathology such as simple steatosis,
      steatohepatitis, fibrosis and cirrhosis. The increased serum levels of
      homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic
      mutations in the folate route may only mildly impair Hcy metabolism. The aim of
      this study was to investigate the relation between liver steatosis with plasma
      homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients
      with NAFLD. METHODS: Thirty-five patients diagnosed with NAFLD by liver biopsy
      and forty-five healthy controls neither age nor sex matched were genotyped for
      C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively,
      and Hcy was determined by HPLC. All patients were negative for markers of
      Wilson's, hemochromatosis and autoimmune diseases. Their daily alcohol intake was
      less than 100 g/week. A set of metabolic and serum lipid markers were also
      measured at the time of liver biopsies. RESULTS: The plasma Hcy level was higher
      in NAFLD patients compared to the control group (p = 0.0341). No statistical
      difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients
      with NAFLD and control subjects was observed. The genotypes distribution was in
      Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group
      of patients and controls showed a statistically significant difference (p <
      0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST,
      ALT, gammaGT, AP and triglycerides levels (p < 0.001). A negative correlation was
      observed between levels of vitamin B12 and Hcy concentration (p = 0.005).
      CONCLUSION: Our results indicate that plasma Hcy was higher in NAFLD than
      controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly
      between groups, despite the 677TT homozygous frequency was higher in patients
      (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic
      susceptibility to the MTHFR C677T and A1298C should be confirmed in large
      population based studies.

PMID- 23547830
TI  - A composite score combining procalcitonin, C-reactive protein and temperature has
      a high positive predictive value for the diagnosis of intensive care-acquired
      infections.
AB  - BACKGROUND: Nosocomial infection diagnosis in the intensive care unit (ICU)
      remains a challenge. We compared routine measurements of procalcitonin (PCT), C
      reactive protein (CRP), white blood cell count (WBC) and temperature in the
      detection of ICU-acquired infections. METHOD: Prospective observational cohort
      study in a University hospital Medicosurgical ICU. All patients admitted to the
      ICU >= 5 days (n = 141) were included into two groups, either infected
      (documented infection, n = 25) or non-infected (discharged from the ICU without
      diagnosis of infection, n = 88). RESULTS: PCT, CRP, WBC and temperature
      progression from day -4 (D-4) to day 0 (D0) (day of infection diagnosis or ICU
      discharge) was analysed. Differences (Delta) were calculated as D0 levels minus
      the lowest preceding value. D0 PCT and CRP were significantly increased in
      infected compared to non-infected patients (median, 1st and 3rd quartiles): 3.6
      ng/mL (0.92-25) for PCT, 173 mg/L (126-188) for CRP versus 0.02 ng/mL (0.1-0.9)
      and 57 mg/mL (31-105) respectively (p < 0.0001). In multivariate analysis, D0
      temperature > 38.6 degrees C, PCT > 1.86 ng/mL, and CRP > 88 mg/L, performed well
      (AUCs of 0.88, 0.84, and 0.88 respectively). The sensitivity/specificity profiles
      of each marker (76%/94% for temperature, 68%/91% for PCT, and 92%/70% for CRP)
      led to a composite score (0.068 * D0 PCT + 0.005 * D0 CRP + 0.7 * temperature)
      more highly specific than each component (AUC of 0.90 and sensitivity/specificity
      of 80%/97%). CONCLUSION: Combining CRP, PCT and temperature is an approach which
      may increase of nosocomial infection detection in the ICU.

PMID- 23547831
TI  - Synthesis of substituted indoline and carbazole by benzyne-mediated cyclization
      functionalization.
AB  - A benzyne-mediated synthesis of substituted indolines and carbazoles was
      developed. The reaction includes generation of benzyne using Mg(TMP)2.2LiCl as a
      base, cyclization, and trapping the resulting organomagnesium intermediate with
      an electrophile to provide a series of substituted indolines and carbazoles in a
      regiospecific manner. This was applied to a concise five-pot total synthesis of
      heptaphylline.

PMID- 23547832
TI  - The myelodysplastic syndromes: a personal recollection of four decades of
      classification and prognostic scoring systems.
AB  - In 1976 the French-American-British (FAB) Leukemia Working Group proposed the
      first definitions of patients with myelodysplastic syndromes (MDS), namely
      refractory anemia with excess blasts (RAEB) and chronic myelomonocytic leukemia
      (CMML). Subsequent publications resulted in additional subgroups that had
      prognostic significance. Incorporation of the subgroupings by the World Health
      Organization and additional fine tuning of the degrees of morphologic dysplasia
      and percentage of blasts have enhanced the classification. Several prognostic
      scoring systems have added degrees of cytopenia, cytogenetic aberrations and
      molecular genetic mutations that allow care providers to subdivide cases into
      lower, intermediate and higher grade categories.

PMID- 23547833
TI  - Bone marrow fibrosis: a prognostic scar in hematological malignancies.

PMID- 23547834
TI  - Overexpression of MIR9 indicates poor prognosis in acute lymphoblastic leukemia.
AB  - Aberrant expression of MIR9 predicts a poor prognosis in acute myelogenous
      leukemia. To evaluate its clinical significance in acute lymphoblastic leukemia,
      we analyzed expression levels of MIR9 in bone marrow samples from patients with
      acute lymphoblastic leukemia and compared them to those in normal bone marrow
      cells. Approximately 20% of them showed higher expression compared with controls.
      There was a tendency that patients who showed overexpression of MIR9 underwent
      worse clinical courses, but without statistical significance. However, when the
      analyses were restricted to patients who did not receive a stem cell transplant,
      overexpression of MIR9 was significantly associated with worse overall survival.
      Interestingly, exaggerated MIR9 expression and higher white blood cell count at
      presentation were independent unfavorable prognostic factors in all patients for
      overall survival by multivariate analysis. The presence of higher MIR9 expression
      could be a useful indicator for treatment stratification.

PMID- 23547835
TI  - Acute lymphoblastic leukemia in adults: encouraging developments on the way to
      higher cure rates.
AB  - Conventional cytotoxic chemotherapy for adult acute lymphoblastic leukemia (ALL)
      is not adequate to cure most patients of the disease. Complete remission is
      achieved in the majority of patients, but responses are often not durable.
      Allogeneic stem cell transplant is used for patients with high risk features,
      including those who are positive for minimal residual disease after induction and
      consolidation therapy. Nevertheless, transplant is a toxic intervention, and does
      not guarantee long-term disease-free survival. Monoclonal antibodies target
      surface antigens present on leukemic blasts, with the aim of minimizing off
      target toxicity. Rituximab, an antibody directed against CD20, prolongs the
      survival of younger adults with ALL when added to chemotherapy in the frontline
      setting. Novel agents, such as the cytotoxin-antibody conjugate inotuzumab, and
      the bispecific T-cell engaging compound blinatumomab, have exhibited marked
      antileukemic activity in the relapsed setting. As these agents continue in
      clinical development, it will be important to eventually incorporate them in the
      frontline treatment approach. We review current strategies for treating adult
      ALL, with a focus on novel and targeted therapies that are under development.

PMID- 23547836
TI  - Deletion or methylation of CDKN2A/2B and PVT1 rearrangement occur frequently in
      highly aggressive B-cell lymphomas harboring 8q24 abnormality.

PMID- 23547837
TI  - Patients with chronic lymphocytic leukemia with high-risk genomic features have
      inferior outcome on successive Cancer and Leukemia Group B trials with
      alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101.
AB  - Alemtuzumab consolidation has been investigated to improve remission duration
      after fludarabine-based induction for chronic lymphocytic leukemia (CLL). The
      impact on genomic high-risk disease remains unknown. Cancer and Leukemia Group B
      (CALGB) 19901 and 10101 enrolled previously untreated patients to receive
      alemtuzumab consolidation after fludarabine-based induction. Immunoglobulin heavy
      chain gene (IGVH) mutation status and interphase cytogenetics were assessed
      retrospectively. Treatment response with these alemtuzumab-containing regimens
      was similar, regardless of genomic risk, except for patients harboring del(17p),
      where few complete remissions were observed. Progression-free survival (PFS) was
      similar between IGVH groups, but overall survival (OS) was inferior in IGVH
      unmutated patients (p = 0.03). Cytogenetic risk group was associated with PFS and
      OS (p = 0.01 for both), with similarly short PFS in patients with del(17p) and
      del(11q) and particularly short OS in patients with del(17p). Cytogenetic risk
      group remained significantly associated with PFS and OS when controlling for
      other prognostic factors (PFS: p = 0.009; OS: p = 0.02), as did the negative
      association of IGVH unmutated disease with OS (p = 0.004). Results were similar
      when restricting to patients who received at least one dose of alemtuzumab
      consolidation, demonstrating limited ability to overcome the poor outcome
      associated with high-risk genetic features.

PMID- 23547838
TI  - Azacytidine for acute myeloid leukemia in elderly or frail patients: a phase II
      trial (SAKK 30/07).
AB  - This phase II trial treated elderly or frail patients with acute myeloid leukemia
      (AML) with single-agent subcutaneous azacytidine at 100 mg/m(2), on 5 of 28 days
      for up to six cycles. Treatment was stopped for lack of response, or continued to
      progression in responders. The primary endpoint was response within 6 months. A
      response rate >= 34% was considered a positive trial outcome. From September 2008
      to April 2010, 45 patients from 10 centers (median age 74 [55-86] years) were
      accrued. Patients received four (1-21) cycles. Best response was complete
      response/complete response with incomplete recovery of neutrophils and/or
      platelets (CR/CRi) in eight (18%; 95% confidence interval [CI]: 8-32%.), 0 (0%)
      partial response (PR), seven (16%) hematologic improvement, 17 (38%) stable
      disease. Three non-responding patients stopped treatment after six cycles, 31
      patients stopped early and 11 patients continued treatment for 8-21 cycles.
      Adverse events (grade >= III) were infections (n = 13), febrile neutropenia (n =
      8), thrombocytopenia (n = 7), dyspnea (p = 6), bleeding (n = 5) and anemia (n =
      4). Median overall survival was 6 months. Peripheral blood blast counts, grouped
      at 30%, had a borderline significant association with response (p = 0.07). This
      modified azacytidine schedule is feasible for elderly or frail patients with AML
      in an outpatient setting with moderate, mainly hematologic, toxicity and response
      in a proportion of patients, although the primary objective was not reached.

PMID- 23547839
TI  - Prognostic factors and risk stratification in early mycosis fungoides.
AB  - Available demographic, clinical, histologic, immunohistochemical and laboratory
      findings, including serum cytokine/cytokine receptor levels, obtained at initial
      evaluation in a cohort of 33 patients with mycosis fungoides (MF) at stages I-IIA
      who had subsequent progression of disease were compared against 70 stage-matched
      cases of MF without observed progression. Significant factors that correlated
      with both disease progression and overall survival were: (1) presence of large
      Pautrier microabscesses (10 or more atypical lymphocytes), (2) presence of
      atypical lymphocytes with hyperchromatic or vesicular nuclei in the dermal
      infiltrate, (3) less than 20% CD8 + cells in the dermal infiltrate and (4) above
      normal (> 122 U/mL) serum immunoglobulin E (IgE) level. Combination of these
      factors was used to construct prognostic groupings which, if validated, might be
      useful to identify patients with clinically early MF at highest risk for disease
      progression and poor outcome.

PMID- 23547840
TI  - Minimal residual disease after allogeneic stem cell transplant: a comparison
      among multiparametric flow cytometry, Wilms tumor 1 expression and chimerism
      status (Complete chimerism versus Low Level Mixed Chimerism) in acute leukemia.
AB  - Relapse represents the main cause of treatment failure after allogeneic stem cell
      transplant (allo-SCT). The detection of minimal residual disease (MRD) by
      multiparametric flow cytometry (MFC), chimerism, cytogenetics and molecular
      analysis may be critical to prevent relapse. Therefore, we assessed the overall
      agreement among chimerism (low level mixed chimerism [LL-MC] vs. complete
      chimerism [CC]), MFC and Wilms tumor 1 (WT1) mRNA to detect MRD and investigated
      the impact of MRD obtained from the three methods on patient outcome. Sixty-seven
      fresh bone marrow (BM) samples from 24 patients (17 acute myeloid leukemia [AML],
      seven acute lymphoblastic leukemia [ALL]) in complete remission (CR) after allo
      SCT were investigated at different time points. A moderate agreement was found
      among the three techniques investigated. A higher concordance between positive
      results from MFC (75.0% vs. 32.7%, p = 0.010) and WT1 (58.3% vs. 29.1%, p =
      0.090) was detected among LL-MC rather than CC samples. Relapse-free survival
      (RFS) and overall survival (OS) were found to be higher in MRD negative patients
      than in MRD positive patients analyzed with MFC and WT1. Our results discourage
      the use of low autologous signals as the only marker of MRD, and suggest the
      usefulness of MFC and WT1 real-time quantitative polymerase chain reaction (RQ
      PCR) in stratifying patients with respect to risk of relapse.

PMID- 23547841
TI  - Methylation of promoters of microRNAs and their host genes in myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) are a group of hematopoietic malignancies
      characterized by ineffective hematopoiesis. Recently, we identified MDS
      associated microRNAs (miRNAs) that are down-regulated in MDS. This study examines
      possible explanations for that observed down-regulation of miRNA expression in
      MDS. Since genomic losses are insufficient to explain the down-regulation of all
      our MDS-associated miRNAs, we explored other avenues. We demonstrate that these
      miRNAs are predominantly intragenic, and that, in many cases, they and their host
      genes are expressed in a similar pattern during myeloid maturation, suggesting
      their co-regulation. This co-regulation is further supported by the down
      regulation of several of the host genes in MDS and increased methylation of the
      shared promoters of several miRNAs and their respective host genes. These studies
      identify a role of hypermethylation of miRNA promoters in the down-regulation of
      MDS-associated miRNAs, unifying research on miRNAs in MDS and epigenetic
      regulation in MDS into a common pathway.

PMID- 23547842
TI  - Hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity
      designed for the targeting of CD44-positive and drug-resistant tumors.
AB  - Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of
      CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we
      report the synthesis of nanogel-drug conjugates based on membranotropic
      cholesteryl-HA (CHA) for efficient targeting and suppression of drug-resistant
      tumors. These conjugates significantly increased the bioavailability of poorly
      soluble drugs with previously reported activity against CSC, such as etoposide,
      salinomycin, and curcumin. The small nanogel particles (diameter 20-40 nm) with a
      hydrophobic core and high drug loads (up to 20%) formed after ultrasonication and
      demonstrated a sustained drug release following the hydrolysis of biodegradable
      ester linkage. Importantly, CHA-drug nanogels demonstrated 2-7 times higher
      cytotoxicity in CD44-expressing drug-resistant human breast and pancreatic
      adenocarcinoma cells compared to that of free drugs and nonmodified HA-drug
      conjugates. These nanogels were efficiently internalized via CD44 receptor
      mediated endocytosis and simultaneous interaction with the cancer cell membrane.
      Anchoring by cholesterol moieties in the cellular membrane after nanogel
      unfolding evidently caused more efficient drug accumulation in cancer cells
      compared to that in nonmodified HA-drug conjugates. CHA-drug nanogels were able
      to penetrate multicellular cancer spheroids and displayed a higher cytotoxic
      effect in the system modeling tumor environment than both free drugs and HA-drug
      conjugates. In conclusion, the proposed design of nanogel-drug conjugates allowed
      us to significantly enhance drug bioavailability, cancer cell targeting, and the
      treatment efficacy against drug-resistant cancer cells and multicellular
      spheroids.

PMID- 23547843
TI  - Cytotoxicity and modulation of cancer-related signaling by (Z)- and (E)-3,4,3',5'
      tetramethoxystilbene isolated from Eugenia rigida.
AB  - Bioassay-guided fractionation of the leaves of Eugenia rigida yielded three
      stilbenes, (Z)-3,4,3',5'-tetramethoxystilbene (1), (E)-3,4,3',5'
      tetramethoxystilbene (2), and (E)-3,5,4'-trimethoxystilbene (3). Their structures
      were determined using 1D- and 2D-NMR spectroscopy and HRESIMS. The sterically
      hindered Z-stereoisomer 1, a new natural product, was prepared by time-dependent
      photoisomerization of the E-isomer (2) under UV irradiation at lambda254 nm,
      while 2,3,5,7-tetramethoxyphenanthrene (5) was identified at lambda365 nm by
      UHPLC/APCI-MS and NMR spectroscopy. Compounds 1-3 were tested against a panel of
      luciferase reporter gene assays that assess the activity of many cancer-related
      signaling pathways, and the Z-isomer (1) was found to be more potent than the E
      isomer (2) in inhibiting the activation of Stat3, Smad3/4, myc, Ets, Notch, and
      Wnt signaling, with IC50 values between 40 and 80 MUM. However, both compounds
      showed similar inhibition against Ap-1 and NF-kappaB signaling. In addition, 1
      demonstrated cytotoxic activity toward human leukemia cells, solid tumor cells of
      epidermal, breast, and cervical carcinomas, and skin melanoma, with IC50 values
      between 3.6 and 4.3 MUM, while 2 was weakly active against leukemia, cervical
      carcinoma, and skin melanoma cells. Interestingly, 2 showed antioxidant activity
      by inhibition of ROS generation to 50% at 33.3 MUM in PMA-induced HL-60 cells,
      while 1 was inactive at 100 MUM (vs Trolox 1.4 MUM).

PMID- 23547844
TI  - Controllable hydrogen sulfide donors and their activity against myocardial
      ischemia-reperfusion injury.
AB  - Hydrogen sulfide (H2S), known as an important cellular signaling molecule, plays
      critical roles in many physiological and/or pathological processes. Modulation of
      H2S levels could have tremendous therapeutic value. However, the study on H2S has
      been hindered due to the lack of controllable H2S releasing agents that could
      mimic the slow and moderate H2S release in vivo. In this work we report the
      design, synthesis, and biological evaluation of a new class of controllable H2S
      donors. Twenty-five donors were prepared and tested. Their structures were based
      on a perthiol template, which was suggested to be involved in H2S biosynthesis.
      H2S release mechanism from these donors was studied and proved to be thiol
      dependent. We also developed a series of cell-based assays to access their H2S
      related activities. H9c2 cardiac myocytes were used in these experiments. We
      tested lead donors' cytotoxicity and confirmed their H2S production in cells.
      Finally we demonstrated that selected donors showed potent protective effects in
      an in vivo murine model of myocardial ischemia-reperfusion injury, through a H2S
      related mechanism. 

PMID- 23547845
TI  - Factors affecting mortality of hospitalized chest trauma patients in United Arab
      Emirates.
AB  - BACKGROUND: Predictors of mortality of chest trauma vary globally. We aimed to
      define factors affecting mortality of hospitalized chest trauma patients in Al
      Ain City, United Arab Emirates. METHODS: The data of Al-Ain Hospital Trauma
      Registry were prospectively collected over a period of three years. Patients with
      chest trauma who were admitted for more than 24 hours in Al-Ain Hospital or who
      died after arrival to the hospital were included in the study. Univariate
      analysis was used to compare patients who died and those who survived. Gender,
      age, nationality, mechanism of injury, systolic blood pressure and GCS on
      arrival, the need for ventilatory support, presence of head injury, AIS for the
      chest and head, presence of injuries outside the chest, and ISS were studied.
      Significant factors were then entered into a backward stepwise likelihood ratio
      logistic regression model. RESULTS: 474 patients having a median (range) age of
      35 (1-90) years were studied. 90% were males and 18% were UAE citizens. The main
      mechanism of injury was road traffic collisions (66%) followed by falls (23.4%).
      Penetrating trauma occurred in 4 patients (0.8%). 88 patients (18.6%) were
      admitted to the ICU. The median (range) ISS was 5 (1-43). 173 patients (36.5%)
      had isolated chest injury. Overall mortality rate was 7.2%. Mortality was
      significantly increased by low GCS (p < 0.0001), high ISS (p = 0.025), and low
      systolic blood pressure on arrival (p = 0.027). CONCLUSION: Chest trauma is
      associated with a significant mortality in Al-Ain City. This was significantly
      related to the severity of head injury, injury severity score, and hypotension on
      arrival.

PMID- 23547846
TI  - Poor mental health in Ghana: who is at risk?
AB  - BACKGROUND: Poor mental health is a leading cause of disability worldwide with
      considerable negative impacts, particularly in low-income countries.
      Nevertheless, empirical evidence on its national prevalence in low-income
      countries, particularly in Africa, is limited. Additionally, researchers and
      policy makers are now calling for empirical investigations of the association
      between empowerment and poor mental health among women. We therefore sought to
      estimate the national prevalence of poor mental health in Ghana, explore its
      correlates on a national level, and examine associations between empowerment and
      poor mental health among women. METHODS: We conducted a cross-sectional analysis
      using data from a nationally representative survey conducted in Ghana in 2009
      2010. Interviews were conducted face-to-face with participants (N = 9,524 for
      overall sample; n = 3,007 for women in relationships). We used the Kessler
      Psychological Distress Scale (K10) to measure psychological distress and assessed
      women's attitudes about their roles in decision-making, attitudes towards
      intimate partner violence, partner control, and partner abuse. We used weighted
      multivariable multinomial regression models to determine the factors
      independently associated with experiencing psychological distress for our overall
      sample and for women in relationships. RESULTS: Overall, 18.7% of the sample
      reported either moderate (11.7%) or severe (7.0%) psychological distress. The
      prevalence of psychological distress was higher among women than men. Overall,
      the prevalence of psychological distress differed by gender, marital status,
      education, wealth, region, health and religion, but not by age or urban/rural
      location. Women who reported having experienced physical abuse, increased partner
      control, and who were more accepting of women's disempowerment had greater
      likelihoods of psychological distress (P-values < 0.05). CONCLUSIONS:
      Psychological distress is substantial among both men and women in Ghana, with
      nearly 20% having moderate or severe psychological distress, an estimate higher
      than those found among South African (16%) or Australian (11%) adults. Women who
      are disempowered in the context of intimate relationships may be particularly
      vulnerable to psychological distress. Results identify populations to be targeted
      by interventions aiming to improve mental health.

PMID- 23547847
TI  - Expanding the scope of replicable unnatural DNA: stepwise optimization of a
      predominantly hydrophobic base pair.
AB  - As part of an ongoing effort to expand the genetic alphabet for in vitro and
      eventually in vivo applications, we have synthesized a wide variety of
      predominantly hydrophobic unnatural base pairs exemplified by d5SICS-dMMO2 and
      d5SICS-dNaM. When incorporated into DNA, the latter is replicated and transcribed
      with greater efficiency and fidelity than the former; however, previous
      optimization efforts identified the para and methoxy-distal meta positions of
      dMMO2 as particularly promising for further optimization. Here, we report the
      stepwise optimization of dMMO2 via the synthesis and evaluation of 18 novel para
      derivatized analogs of dMMO2, followed by further derivatization and evaluation
      of the most promising analogs with meta substituents. Subject to size
      constraints, we find that para substituents can optimize replication via both
      steric and electronic effects and that meta methoxy groups are unfavorable, while
      fluoro substituents can be beneficial or deleterious depending on the para
      substituent. In addition, we find that improvements in the efficiency of
      unnatural triphosphate insertion translate most directly into higher fidelity
      replication. Importantly, we identify multiple, unique base pair derivatives that
      when incorporated into DNA are well replicated. The most promising, d5SICS-dFEMO,
      is replicated under some conditions with greater efficiency and fidelity than
      d5SICS-dNaM. These results clearly demonstrate the generality of hydrophobic
      forces for the control of base pairing within DNA, provide a wealth of new SAR
      data, and importantly identify multiple new candidates for eventual in vivo
      evaluation.

PMID- 23547848
TI  - Pharmacokinetics and pharmacodynamics of tocilizumab, a humanized anti
      interleukin-6 receptor monoclonal antibody, following single-dose administration
      by subcutaneous and intravenous routes to healthy subjects.
AB  - OBJECTIVES: Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R)
      monoclonal antibody, given by intravenous (i.v.) infusion every 4 weeks has been
      approved for treatment of patients with rheumatoid arthritis. The objective of
      the study was to determine pharmacokinetics (PK) and pharmacodynamics (PD) of
      tocilizumab including absolute PK and PD bioavailabilities following subcutaneous
      (s.c.) administration. METHODS: The PK and PD of tocilizumab 162 mg or 81 mg
      after single s.c. and i.v. administration were evaluated in an open-label, 4
      parallel group study involving 48 healthy subjects (n = 12/group). RESULTS:
      Following single-dose s.c. administration of tocilizumab, area under the serum
      concentration-time curve (AUCinfinity) increased by 6.4-fold, and maximum serum
      concentration (Cmax) increased by 4-fold, as the dose was doubled from 81 mg to
      162 mg. Tocilizumab absolute PK bioavailability (AUCinfinity ratio (s.c./i.v.))
      was higher at 162 mg (48.8%) than at 81 mg (22.7%). Tocilizumab PD
      bioavailability for soluble IL-6R (sIL-6R) (AUClast ratio (s.c./i.v.)) was 109%
      at 162 mg and 80.9% at 81 mg. Tocilizumab PD bioavailability for C-reactive
      protein (CRP) effect was 98.2% (CRP AUC480h ratio) at 162 mg and 80.4% (AUC240h
      ratio (s.c./i.v.)) at 81 mg. Tocilizumab was well tolerated at both doses after
      s.c. and i.v. administration. CONCLUSIONS: Tocilizumab absolute PK
      bioavailability for s.c. vs. i.v. administration was low; however, the PD effects
      for sIL-6R and CRP levels were comparable after 162-mg s.c. and i.v.
      administration. Therefore, 162 mg s.c. dose is a comparable dose for 162 mg i.v.
      dose based on PD bioavailability.

PMID- 23547849
TI  - Pharmacokinetics and pharmacodynamics of single subcutaneous doses of tocilizumab
      administered with or without rHuPH20.
AB  - OBJECTIVES: To investigate the safety, tolerability, pharmacokinetics (PK), and
      pharmacodynamics (PD) of tocilizumab with and without rHuPH20 (a recombinant
      human hyaluronidase) in healthy volunteers. METHODS: This was an open-label,
      single ascending dose study. Subjects were assigned to tocilizumab 162 mg or
      tocilizumab 162, 324, or 648 mg plus rHuPH20. PK and PD samples were collected
      after dosing and were estimated with non-compartmental methods. Geometric mean
      ratio (GMR) for area under the plasma concentration-time curve from zero to
      infinity (AUC0-infinity) and (maximum serum concentration) Cmax with and without
      rHuPH20 was estimated using one-way analysis of variance. Safety and tolerability
      were monitored throughout the study. RESULTS: 48 subjects (12/cohort) received a
      single dose of tocilizumab with or without rHuPH20. For tocilizumab 162 mg,
      tocilizumab 162 mg/rHuPH20, tocilizumab 324 mg/rHuPH20, and tocilizumab 648
      mg/rHuPH20, mean +/- SD tocilizumab PK parameters were 2,510 +/- 1,060, 2,860 +/-
      468, 10,800 +/- 3,220, and 29,900 +/- 5,280 MUg*h/ml for AUC0-infinity; 11.5 +/-
      3.7, 16.2 +/- 2.8, 43.8 +/- 12.4, and 77.8 +/- 14.5 MUg/ml for Cmax; and 89.1 +/-
      41.1, 54.0 +/- 19.5, 66.0 +/- 26.8, and 86.1 +/- 50.6 h for tmax, respectively.
      Coadministration of tocilizumab 162 mg with rHuPH20 resulted in slightly
      increased exposure: GMR (90% confidence interval) for AUC0-infinity, 1.20 (1.00 -
      1.44) and Cmax, 1.45 (1.24 - 1.70). Increasing tocilizumab doses resulted in
      significant deviation from dose proportionality for tocilizumab Cmax (p = 0.0057)
      and AUC0-infinity (p < 0.0001). Changes in interleukin-6, soluble interleukin- 6
      receptor, and C-reactive protein were also dose dependent and similar with and
      without rHuPH20. CONCLUSIONS: Tocilizumab in combination with rHuPH20 resulted in
      slightly increased tocilizumab exposure compared with tocilizumab alone, whereas
      PD markers were comparable. Subcutaneous administration of tocilizumab with
      rHuPH20 was well tolerated.

PMID- 23547850
TI  - Genetic polymorphisms associated with oxaliplatin-induced peripheral
      neurotoxicity in Japanese patients with colorectal cancer.
AB  - OBJECTIVE: Pharmacogenomic associations between severe oxaliplatininduced chronic
      peripheral neurotoxicity (OXCPN) (Grade 2 lasting for > 7 days or Grade 3) and 9
      single nucleotide polymorphisms (SNPs) in 8 genes (TAC1, FOXC1, ITGA1, ACYP2,
      DLEU7, BTG4, CAMK2N1, and FARS2) were reported by the genomewide association
      study (GWAS) in Korean patients. The present study was designed to explore
      reliable predictors of OXCPN and thereby improve the management of metastatic
      colorectal cancer (CRC). METHODS: We retrospectively investigated pharmacogenomic
      characteristics of OXCPN in 70 Japanese patients with CRC who received
      oxaliplatin-based chemotherapy and updated the results of our previous analysis
      of ERCC1 (C118T, rs11615 and C8092A, rs3212986) and GSTP1 (Ile105Val, rs1695)
      polymorphisms. RESULTS: Univariate analysis suggested potential associations of
      severe OXCPN with rs843748 in ACYP2 and rs17140129 in FARS2, as well as with the
      absence of diabetes mellitus (DM) (p = 0.056, 0.072, and 0.029, respectively).
      There was no association between severe OXCPN and any of the 7 other SNPs.
      Multiple logistic regression analysis showed that an increased risk of severe
      OXCPN was related to rs17140129 and the absence of DM (p = 0.034 and 0.030,
      respectively). On updated analysis, polymorphisms of ERCC1 (C118T, rs11615) and
      rs10486003 in TAC1 were associated with time to the onset of Grade 1 OXCPN (p =
      0.024 and 0.049, respectively). CONCLUSIONS: Severe OXCPN is significantly
      related to rs17140129, found in the GWAS of Korean patients, in Japanese
      patients. Patients without DM are more likely to have OXCPN. The association
      between ERCC1 polymorphism and time to the onset of OXCPN was significant on
      updated analysis.

PMID- 23547851
TI  - Superior efficacy of azithromycin and levamisole vs. azithromycin in the
      treatment of inflammatory acne vulgaris: an investigator blind randomized
      clinical trial on 169 patients.
AB  - BACKGROUND: Different immunologic mechanisms contribute to development of
      inflammation in acne vulgaris and immunologic effect of levamisole has been
      demonstrated. OBJECTIVE: The aim of this study was to compare azithromycin and
      levamisole with azithromycin alone in the treatment of acne vulgaris. METHODS: An
      investigator-blind clinical randomized prospective 2 months study was designed.
      169 acne patients presenting in our outpatients clinic were randomly allocated to
      two treatment groups: azithromycin and levamisole (Group 1) and azithromycin
      alone (Group 2). 148 patients completed the duration of the study and their
      clinical responses were evaluated and compared by using monthly photographic
      records. RESULTS: Mean reduction rates for the number of papules, pustules and
      both of them, in Group 1 were 73.72%, 82.69% and 76.93%, respectively, and
      68.39%, 70.89% and 69.32% in Group 2 (p < 0.05). Also, mean reduction rates for
      the number of nodules, cysts and both of them in Group 1 were 80.97%, 89.75% and
      82.35%, respectively, and 58.54%, 54.55% and 57.99% in Group 2 (p < 0.05).These
      differences between two groups were statistically significant in favor of
      azithromycin and levamisole (Group 1) (p < 0.05). CONCLUSION: According to this
      study azithromycin plus levamisole may be more effective than azithromycin alone
      in decreasing of inflammatory acne lesions especially in nodulocystic form. So,
      regarding the low cost and side effect profile of levamisole, we suggest to
      consider combination of levamisole with azithromycin while facing acne patients
      at least with more inflammatory lesions especially when there is any
      contraindication for isotretinoin.

PMID- 23547852
TI  - A limited sampling strategy for tacrolimus in liver transplant patients.
AB  - To develop limited sampling strategy (LSS) equations to estimate area under the
      curve (AUC0-12) in Chinese adult transplant patients. 26 adult liver transplant
      patients were included in this study. The blood samples, collected within 12
      hours, were analyzed by microparticle enzyme immunoassay. By multiple stepwise
      linear regression analysis, LSS equations were identified. The predictive
      performance of these models was validated by the jackknife technique. As a
      result, the two sampling time point (trough and 4 hours postdose) model
      accurately predicted AUC0-12. (R2 = 0.949, ICC = 0.976). The two-point LSS
      equation (AUC0-12 = 7.26 + (2.17.C0) + (8.30.C4)) can be used as a predictable
      measure of AUC0-12 of tacrolimus in Chinese liver transplant patients.

PMID- 23547853
TI  - Current situation of clinical trials in Beijing and Shanghai, China.
AB  - OBJECTIVE: Global clinical trials are important because they facilitate rapid
      delivery of new and effective drugs to patients Assessment of the current
      situation of clinical trials conducted in Asia is critical for improving
      performance of global clinical trials. However, review reports from China or
      other Asian countries are not yet available. Therefore, the purpose of this
      research was to investigate the current quality of clinical trials conducted in
      Shanghai, as well as Beijing. METHODS: Questionnaires were distributed to medical
      doctors attending institutes in Beijing and Shanghai in which clinical trials
      have been conducted. These questionnaires were delivered and collected from both
      areas by the Peking University research team of Beijing and the Fudan University
      research team of Shanghai respectively. Analysis and evaluation were conducted by
      research teams from both China and Japan. RESULTS: Subjects were randomly
      selected by the respective research team. A total of 145 questionnaires in
      Beijing and 162 in Shanghai were administered: all 307 questionnaires were
      completed. In total, 57.2% and 74.5% of respondents from Beijing and Shanghai,
      respectively, reported participation in audits and inspections on an annual basis
      conducted by their own institute. A total of 49.2% and 56.0% of respondents from
      Beijing and Shanghai, respectively, reported that they received reports after the
      audits and inspections by an institute. 23.5% and 37.7% of respondents from
      Beijing and Shanghai, respectively, reported participation in audits conducted
      annually by external authorities. A total of 18.9% and 29.5% of respondents from
      Beijing and Shanghai, respectively, reported that they received reports after the
      audits and inspections by an external authority. CONCLUSIONS: Our research
      suggests that clinical trials in Shanghai, as well as in Beijing, are conducted
      vigorously and appropriately monitored by audits and inspections conducted by
      concerned institutes and/or by an external authority.

PMID- 23547854
TI  - Pregabalin abuse after past substance-seeking behavior.
AB  - Pregabalin is a prescription drug, structurally related to the neurotransmitter
      GABA. Following the rapidly increasing use of pregabalin, data signaling its
      abuse liability have been published recently. We report a case of a 19-year-old
      man with a history of cannabis and alcohol-seeking behavior that showed similar
      drug-seeking behavior with pregabalin. This report highlights the potential for
      abuse of pregabalin in patients with a history of substance-seeking behavior.
      Considering that the drug has recently been proposed as a treatment for alcohol-
      and benzodiazepine-dependence a better clarification of its abuse potential is
      essential.

PMID- 23547855
TI  - Frequency of hospitalizations prior to and after conversion to a rebate
      pharmaceutical in depression patients in Germany.
AB  - BACKGROUND: The aim of this study was to investigate the frequency of
      hospitalization in depression patients with and without conversion to a rebate
      pharmaceutical and to show the negative consequences of rebate contracts on the
      health of patients with depression. METHODS: This retrospective study was
      performed using two databases that included data on ~ 10 millions patients
      gathered between July 2009 and June 2012. This study included adults (> 18 years)
      on an antidepressive drug therapy who had statutory health insurance with rebate
      contracts on antidepressive pharmaceuticals. RESULTS: In total, 47,968 patients
      on an antidepressive drug therapy were included in the persistence analysis using
      the IMS Disease Analyzer database. Of those, 26,651 patients were converted to a
      rebate product whereas 21,317 patients continued with the initial pharmaceutical
      product. After adjusting for the majority of demographic and clinical variables,
      the risk of hospitalization was 57% higher in patients who switched to a rebate
      pharmaceutical in comparison to patients who did not. When projected to the
      national level, this was found to equal an additional 34,157 patients
      hospitalized due to conversion to a rebate pharmaceutical resulting in direct
      inpatient costs amounting to 363.8 million EUR per year in Germany. CONCLUSIONS:
      Despite some limitations, this analysis presents a clear association between the
      initiation of rebate contracts and a negative impact on the health of patients on
      an antidepressive drug therapy.

PMID- 23547857
TI  - Factor XI and traveling waves: the key to understanding coagulation in
      hemophilia?

PMID- 23547856
TI  - Species and condition specific adaptation of the transcriptional landscapes in
      Candida albicans and Candida dubliniensis.
AB  - BACKGROUND: Although Candida albicans and Candida dubliniensis are most closely
      related, both species behave significantly different with respect to
      morphogenesis and virulence. In order to gain further insight into the divergent
      routes for morphogenetic adaptation in both species, we investigated qualitative
      along with quantitative differences in the transcriptomes of both organisms by
      cDNA deep sequencing. RESULTS: Following genome-associated assembly of sequence
      reads we were able to generate experimentally verified databases containing 6016
      and 5972 genes for C. albicans and C. dubliniensis, respectively. About 95% of
      the transcriptionally active regions (TARs) contain open reading frames while the
      remaining TARs most likely represent non-coding RNAs. Comparison of our
      annotations with publically available gene models for C. albicans and C.
      dubliniensis confirmed approximately 95% of already predicted genes, but also
      revealed so far unknown novel TARs in both species. Qualitative cross-species
      analysis of these databases revealed in addition to 5802 orthologs also 399 and
      49 species-specific protein coding genes for C. albicans and C. dubliniensis,
      respectively. Furthermore, quantitative transcriptional profiling using RNA-Seq
      revealed significant differences in the expression of orthologs across both
      species. We defined a core subset of 84 hyphal-specific genes required for both
      species, as well as a set of 42 genes that seem to be specifically induced during
      hyphal morphogenesis in C. albicans. CONCLUSIONS: Species-specific adaptation in
      C. albicans and C. dubliniensis is governed by individual genetic repertoires but
      also by altered regulation of conserved orthologs on the transcriptional level.

PMID- 23547858
TI  - Could statins be a new therapeutic option for antiphospholipid syndrome patients?

PMID- 23547860
TI  - Bendamustine for non-Hodgkin lymphoma. Interview by Louise Rishton.
AB  - Professor John Gribben is Chair of the International Workshop on non-Hodgkin
      Lymphoma and the Gordon Hamilton Fairley Chair of Medical Oncology at St.
      Bartholomew's Hospital, Bart's Cancer Institute, London, UK, a Cancer Research UK
      Centre of Excellence. His doctoral studies were performed at University College
      London, UK as the recipient of a Wellcome Trust Fellowship Award and he continued
      post-doctoral training with Professor Lee Nadler at the Dana-Farber Cancer
      Institute (Harvard Medical School, MA, USA). In 1992, Gribben was appointed to
      the Faculty at Harvard Medical School, where he remained as Associate Professor
      of Medicine and an Attending Physician at the Dana-Farber Cancer Institute and
      Brigham and Women's Hospital (MA, USA), until returning to London in 2005.
      Gribben is a founding member of the CLL Research Consortium, Associate Editor of
      Blood and was elected a Fellow of the Academy of Medical Science. His primary
      research interests include the immunotherapy of cancer (including stem cell
      transplantation), the identification of B-cell-tumor antigens and the detection
      and treatment of minimal residual disease in leukemia and lymphoma.

PMID- 23547861
TI  - Highlights in acute myeloid leukemia from the 2012 meeting of the American
      Society of Hematology.
AB  - The American Society of Hematology Annual Meeting includes physicians,
      scientists, administrators, medical students, graduate students, allied health
      professionals and exhibitors. This year's meeting was held in Atlanta, GA, USA.
      Presentations included a wide variety of topics in benign and malignant
      hematology.

PMID- 23547862
TI  - Prophylactic use of granulocyte colony-stimulating factor after consolidation
      therapy with high-dose cytarabine for acute myeloid leukemia.
AB  - Prophylactic use of granulocyte colony-stimulating factor after chemotherapy in
      acute myeloid leukemia patients has become part of the supportive care strategy
      in some institutions. Despite shortening the neutropenia period and lowering the
      hospitalization rate, randomized studies have not shown any improvement in the
      clinical outcomes with this intervention. In their single-institution
      retrospective study, Bradley et al. reported that granulocyte colony-stimulating
      factor administration following consolidation therapy with high-dose cytarabine
      is associated with decreased hospitalization rate and improved survival. This
      finding is not consistent with the prior knowledge from the randomized studies.
      Herein, we review some of the explanations for the findings and re-emphasize the
      limitations of nonrandomized studies in assessing acute myeloid leukemia
      outcomes, as appreciated by the authors.

PMID- 23547863
TI  - Low-molecular-weight heparin versus rivaroxaban in orthopedic surgery.
AB  - From the ORTHO-TEP registry on joint replacement arthroplasty (hip and knee) from
      Dresden, Germany, three periods of different prophylactic regimens have been
      compared. In the present paper, results from low-molecular-weight heparin and
      rivaroxaban have been analyzed, with rivaroxaban showing a benefit concerning
      both effect and side effects. Clinical end points are used, the results being in
      line with published data from randomized studies. Inclusion in the registry of
      consecutive patients is important to illustrate generalizability of results
      obtained in randomized trials. This review discusses the problem with using
      historical comparisons to draw firm conclusions.

PMID- 23547864
TI  - Atypical lymphoid proliferations: the pathologist's viewpoint.
AB  - Lymphoid proliferations are traditionally thought to be either benign conditions
      (reactive hyperplasia and lymphadenitis) or malignant lymphomas. However, not all
      lymphoid lesions at present can be precisely placed into one of these categories.
      Therefore, in addition to these two extremes, there also exist a third group of
      lymphoid proliferations - the atypical lymphoid proliferations (AtLP). AtLP is a
      descriptive term used when it is not possible for the pathologist to
      differentiate between the benign and the malignant nature of a given lymphoid
      infiltrate. AtLP represent biologically indeterminate lesions that have some
      worrisome clinicopathologic features but cannot be interpreted as malignant
      lymphomas using all criteria currently available. They have some likelihood for
      subsequent transformation into lymphomas, and therefore AtLP occupy a middle
      ground between benign and malignant lymphoid proliferations. Nevertheless,
      sometimes AtLP are not necessarily premalignant and may very well represent a
      fully benign situation mimicking malignancy. In the author's opinion, when
      confronted with a challenging lymphoproliferative lesion, the pathologist should
      marshall all resources available to interpret it as precisely as possible and
      therefore place it into one of the two categories: unequivocally benign condition
      or malignant lymphomas. The resources should include immunohistochemical and
      molecular studies, obtaining expert opinion and rebiopsy. However, if clinical,
      morphologic and molecular findings are not sufficient for diagnosis of a benign
      condition versus lymphoma, the descriptive term AtLP can be used. In the author's
      opinion, the use of this descriptive term AtLP may obviate the need to force some
      lymphoid proliferations (equivocal lesions or mimickers of lymphomas) into either
      the benign or malignant categories.

PMID- 23547865
TI  - Monitoring plasma levels of factor Xa inhibitors: how, why and when?
AB  - New oral anticoagulants are directed towards a single target, essentially factor
      Xa (FXa) or factor IIa. They do not require routine coagulation monitoring.
      However, in special clinical settings (emergency surgery, bleeding, thrombosis,
      control of the patient's compliance, suspected overdose, potential drug
      interference, and so on), measurement of plasma levels is needed. Several
      available anti-FXa assays are used for monitoring anticoagulant activity of
      heparins and fondaparinux. They must be modified and standardized for the
      measurement of direct FXa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban
      and others). The use of calibrators (lyophilized plasma with a known
      concentration of drug) allows an expression of the results in ng per ml of
      plasma. Two categories of assays - endogenous and exogenous assays are available.
      Endogenous assays are useful in pharmaceutical research, while exogenous assays
      are used in clinical laboratories. The preferred anti-FXa assay is a specific
      method in contrast to prothrombin time and activated partial thromboplastin time,
      but it is not available everywhere at any time. A specific measurement of direct
      FXa inhibitors is feasible with the use of a new test developed by the authors'
      group. The physicians must be aware of the possibility to measure the plasma
      concentration of FXa inhibitors in patients at high risk of bleeding and in
      several other special clinical situations.

PMID- 23547866
TI  - Review of therapeutic options and the management of patients with myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) are a poorly understood group of disorders caused
      by one or more genetic aberrations in the bone marrow-derived cell line
      responsible for hematopoiesis. Recent advances in genetic medicine have offered
      new insights into the epigenesis as well as the prognosis of MDS, but have not
      resulted in new or improved curative treatment options. Bone marrow
      transplantation, introduced before the advent of genetic medicine, is still the
      only potential cure. Advances in other medical and pharmaceutical areas have
      broadened the scope of supportive care and disease-modifying therapies, and
      treating physicians now have a broad range of disease management options
      depending on a patient's likely prognosis. There is now clear evidence that
      appropriate supportive care and therapeutic intervention can improve progression
      free and overall survival of MDS patients.

PMID- 23547867
TI  - The current status and future impact of targeted therapies in non-Hodgkin
      lymphoma.
AB  - A number of new, biologic targeted therapies have been developed for the
      treatment of lymphoid malignancies. These include anti-CD20 monoclonal antibodies
      designed with greater binding affinities and different mechanisms of action
      profiles compared with rituximab. Other extracellular antigens on B cells and T
      cells are also being targeted. Monoclonal antibodies have been conjugated to
      radioisotopes and cellular toxins. In addition, several exciting new small
      molecule kinase inhibitors are in development that target intracellular pathways
      that contribute to the pathogenesis of these diseases. Drugs that affect the
      tumor microenvironment are also under investigation. The advantage of these
      targeted agents compared with standard chemotherapy is greater tumor specificity,
      a more favorable toxicity profile, and, when combined with scientific rationale,
      and in the appropriate setting, perhaps a better long-term outcome.

PMID- 23547868
TI  - Platelet biology: the role of shear.
AB  - Platelets are anucleated fragments produced by megakaryocytes that circulate in
      the blood. Platelets are involved in the initial cellular response to damaged
      endothelium and migrate to this area to prevent excessive bleeding. What is
      becoming more acknowledged over the last few decades is that blood flow
      (hemodynamics) plays a critical role in platelet function. The purpose of this
      review is to summarize the current understanding of platelet biology with
      particular focus on the role of hemodynamics. The emerging concept of shear
      microgradients, which are challenging the traditional model of platelet function,
      will also be introduced in the review.

PMID- 23547870
TI  - Biodegradation of 2,4-dinitrophenol with laccase immobilized on nano-porous
      silica beads.
AB  - Many organic hazardous pollutants, including 2,4-dinitrophenol (2,4-DNP), which
      are water soluble, toxic, and not easily biodegradable make concerns for
      environmental pollution worldwide. In the present study, degradation of
      nitrophenols-contained effluents by using laccase immobilized on the nano-porous
      silica beads was evaluated. 2,4-DNP was selected as the main constituent of
      industrial effluents containing nitrophenols. The performance of the system was
      characterized as a function of pH, contact time, temperature, pollutant, and
      mediator concentrations. The laccase-silica beads were employed in a mixed-batch
      reactor to determine the degradation efficiency after 12 h of enzyme treatment.
      The obtained data showed that the immobilized laccase degraded more than 90% of
      2,4-DNP within 12 h treatment. The immobilization process improved the activity
      and sustainability of laccase for degradation of the pollutant. Temperatures more
      than 50 degrees C reduced the enzyme activity to about 60%. However, pH and the
      mediator concentration could not affect the enzyme activity. The degradation
      kinetic was in accordance with a Michaelis-Menten equation with Vmax and Km
      obtained as 0.25-0.38 MUmoles/min and 0.13-0.017 mM, respectively. The stability
      of the immobilized enzyme was maintained for more than 85% of its initial
      activity after 30 days. Based on the results, it can be concluded that high
      resistibility and reusability of immobilized laccase on CPC-silica beads make it
      considerable choice for wastewater treatment. 

PMID- 23547871
TI  - Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing
      spondylitis.
AB  - OBJECTIVES: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3)
      inflammasome is important for interleukin-1beta (IL-1beta) processing as part of
      an innate immune response. Caspase recruitment domain family, member 8 (CARD8) is
      an inhibitor of nuclear factor kappa B (NF-kappaB) and possibly also a part of
      the NLRP3 inflammasome. The objective of this study was to evaluate one single
      nucleotide polymorphism (SNP) in CARD8 and three SNPs in NLRP3 in ankylosing
      spondylitis (AS) susceptibility and disease phenotype. METHOD: We recruited 492
      AS patients from Southern Sweden fulfilling the modified New York criteria for
      AS, and assessed phenotypic characteristics from medical records and
      questionnaires. Patients with psoriasis or clinically overt inflammatory bowel
      disease (IBD) were excluded, as were patients without human leucocyte antigen B27
      (HLA-B27). Three NLRP3 SNPs (rs35829419, rs4353135, and rs10733113) and one SNP
      in CARD8 (rs2043211) were genotyped by commercially available TaqMan assays, and
      the results compared at genotype and allele levels to those of 793 population
      based controls. In a subgroup of the patients (n = 169), faecal calprotectin was
      assessed as a marker of subclinical intestinal inflammation. RESULTS: The minor
      allele (A) of CARD8-C10X (rs2043211) was associated with a decreased risk of AS
      in a dominant model [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54
      0.94, p = 0.012] and at the allelic level (OR 0.81, 95% CI 0.68-0.97, p = 0.02),
      but was not associated with levels of faecal calprotectin. There was no
      association regarding NLRP3 SNPs and AS susceptibility, and none of the
      investigated SNPs were associated with iritis, anti-tumour necrosis factor (anti
      TNF) therapy, or peripheral joint involvement. CONCLUSION: In a Swedish
      population, the minor allele of CARD8-C10X is associated with a decreased risk of
      AS, but not with levels of faecal calprotectin or disease phenotype.

PMID- 23547872
TI  - Interfacial nanoarchitectonics: lateral and vertical, static and dynamic.
AB  - The exploration of nanostructures and nanomaterials is essential to the
      development of advanced functions. For such innovations, nanoarchitectonics has
      been proposed as a novel paradigm of nanotechnology aimed at assembling nanoscale
      structural units into predesigned configurations or arrangements. In this Feature
      Article, we provide an overview of several recent research works from the
      viewpoint of interfacial nanoarchitectonics with features developed in lateral
      directions or grown in vertical directions with construction on solid, static, or
      flexible dynamic surfaces. Lateral nanoarchitectonics at a static interface
      provides molecular organization by bottom-up nanoarchitectonics and can also be
      used to realize device integration by top-down nanoarchitectonics. In particular,
      in the latter case, the fabrication of novel devices, so-called atomic switches,
      are introduced as a demonstration of atomic-level electronics. Lateral
      nanoarchitectonics at dynamic interfaces is exemplified by 2D molecular
      patterning and molecular machine operation induced by macroscopic motion. The
      dynamic nature of interfaces enables us to operate molecular-sized machines by
      macroscopic mechanical stimuli such as our hand motion, which we refer to as hand
      operated nanotechnology. Vertical nanoarchitectonics is mainly discussed in
      relation to layer-by-layer (LbL) assembly. By using this technique, we can
      assemble a variety of functional materials in ultrathin film structures of
      defined thickness and layer sequence. The organization of biomolecules (or even
      living cells) within thin films and their integration with device structures is
      exemplified. Finally, the anticipated research directions of interfacial
      nanoarchitectonics are described. 

PMID- 23547873
TI  - Structurally differentiated cis-elements that interact with PU.1 are functionally
      distinguishable in acute promyelocytic leukemia.
AB  - BACKGROUND: Transcription factor PU.1, a member of the ETS family, is a master
      regulator of myeloid differentiation whose functional disruption is often
      associated with acute myeloid leukemia (AML). Although much has been learned
      about PU.1 over the past decades, relatively little is known about cis-elements
      that interact with this factor under physiological or pathological conditions,
      especially in the whole-genome scale. We aimed to define the cistrome of PU.1 in
      acute promyelocytic leukemia (APL) cells and characterize the cis-elements bound
      by PU.1. METHODS: Chromatin immunoprecipitation with specific antibody coupled
      with deep sequencing (ChIP-seq) was used to investigate the in vivo PU.1 binding
      sites at the whole-genome scale in APL-derived NB4 cells. The ChIP-quantitative
      (q)-PCR and luciferase reporter assays were used to validate the binding events
      and trans-activity, respectively. Various computational analyses, including motif
      mining, evolutionary conservation analysis and functional enrichment analysis,
      were performed to characterize the cis-elements that interacted with PU.1.
      RESULTS: A total of 26,907 significantly enriched binding regions of PU.1 were
      identified under the false discovery rate 0.1% in NB4 cells. PU.1 bound to
      various types of genomic regions and acted as a promoter-enhancer dual binding
      transcription factor. Based on the sequence length and composition, two types of
      representative motifs were identified in PU.1 binding sites: a long and a short
      motif. The long motif, characterized by high sequence specificity and binding
      affinity, predominantly resided in the promoter-distal regions. In contrast, the
      short one, with strong evolutionary constraint, represented the primary PU.1 cis
      elements in the promoter-proximal regions. Interestingly, the short one showed
      more preference to be correlated with the binding of other factors, especially
      PML/RARalpha. Moreover, genes targeted by both PU.1 and PML/RARalpha were
      significantly involved in categories associated with oncogenesis, hematopoiesis
      and the pathogenesis of acute myeloid leukemia. CONCLUSIONS: Our results
      demonstrate that structurally differentiated cis-elements that interact with PU.1
      are functionally distinguishable in APL, suggesting that the sequence diversity
      of cis-elements might be a critical mechanism by which cells interpret the
      genome, and contribute to distinct physiological and/or pathological function.

PMID- 23547874
TI  - Synthesis of novel steroid derivatives derived from dehydroepiandrosterone as
      potential anticancer agents.
AB  - A series of dehydroepiandrosterone derivatives containing dihydrazone unit was
      synthesized via a convenient condensation procedure, and which were evaluated for
      their potential anticancer activities. The preliminary assays indicated that some
      of the newly synthesized compounds exhibited good antitumor activities against
      human hepatocellular liver carcinoma (HepG2), heptoma (Huh-7), gastric cancer
      (BGC-823) and breast adenocarcinoma (MCF-7) cell lines compared with 5
      fluorouracil (5-FU), which might be considered as promising lead scaffold for
      further design and synthesis of potential anticancer agents. 

PMID- 23547875
TI  - Thalamus, brainstem and salience network connectivity changes during propofol
      induced sedation and unconsciousness.
AB  - In this functional magnetic resonance imaging study, we examined the effect of
      mild propofol sedation and propofol-induced unconsciousness on resting state
      brain connectivity, using graph analysis based on independent component analysis
      and a classical seed-based analysis. Contrary to previous propofol research,
      which mainly emphasized the importance of connectivity in the default mode
      network (DMN) and external control network (ECN), we focused on the salience
      network, thalamus, and brainstem. The importance of these brain regions in brain
      arousal and organization merits a more detailed examination of their connectivity
      response to propofol. We found that the salience network disintegrated during
      propofol-induced unconsciousness. The thalamus decreased connectivity with the
      DMN, ECN, and salience network, while increasing connectivity with sensorimotor
      and auditory/insular cortices. Brainstem regions disconnected from the DMN with
      unconsciousness, while the pontine tegmental area increased connectivity with the
      insulae during mild sedation. These findings illustrate that loss of
      consciousness is associated with a wide variety of decreases and increases of
      both cortical and subcortical connectivity. It furthermore stresses the necessity
      of also examining resting state connectivity in networks representing arousal,
      not only those associated with awareness.

PMID- 23547876
TI  - Kinetics of arsenite removal by halobacteria from a highland Andean Chilean
      Salar.
AB  - BACKGROUND: The purpose of this study was to identify arsenite-oxidizing
      halobacteria in samples obtained from Salar de Punta Negra, II Region of Chile.
      Seven bacterial isolates, numbered as isolates I to VII, grown in a culture
      medium with 100 ppm as NaAsO2 (As (III)) were tested. Bacterial growth kinetics
      and the percent of arsenite removal (PAR) were performed simultaneously with the
      detection of an arsenite oxidase enzyme through Dot Blot analysis. RESULTS: An
      arsenite oxidase enzyme was detected in all isolates, expressed constitutively
      after 10 generations grown in the absence of As (III). Bacterial growth kinetics
      and corresponding PAR values showed significant fluctuations over time. PARs
      close to 100% were shown by isolates V, VI, and VII, at different times of the
      bacterial growth phase; while isolate II showed PAR values around 40%, remaining
      constant over time. CONCLUSION: Halobacteria from Salar de Punta Negra showed
      promising properties as arsenite removers under control conditions, incubation
      time being a critical parameter.

PMID- 23547877
TI  - Maternal iron intake at mid-pregnancy is associated with reduced fetal growth:
      results from Mothers and Children's Environmental Health (MOCEH) study.
AB  - BACKGROUND: Iron supplementation is a common recommendation for pregnant women to
      prevent iron deficiency during pregnancy. There is an increasing concern about
      excessive iron consumption as a general iron prophylaxis by pregnant women
      without any due consideration about their dietary iron intake or iron status. Our
      present study investigated the association between total iron intake from diet
      and supplements and fetal growth in 337 pregnant women at mid-pregnancy in South
      Korea. METHODS: Iron intake from diet and supplements was examined by a 24-hour
      recall method. Subjects were divided into three groups based on tertiles of total
      iron intake levels. Fetal biometry was assessed by ultrasonography at mid
      pregnancy. RESULTS: About 99% of the non-supplement users had iron intake below
      the recommended nutrient intake (RNI) for pregnant women (24 mg), whereas 64.9%
      of supplement users had iron intake above the upper level (UL) (45 mg). In the
      babies of mothers in the third tertile of iron intake (>17.04 mg), biparietal
      diameter, abdominal circumference, and femur length were lower by 0.41 cm (P
      =0.019), 0.41 cm (P = 0.027), and 0.07 cm (P = 0.051), respectively, than the
      babies of mothers in the second tertile of iron intake (11.49 ~ 17.04 mg).
      CONCLUSION: These results suggest that excessive maternal iron intake at mid
      pregnancy is associated with reduced fetal growth. Iron supplementation for
      pregnant women should be individualized according to their iron status.
      Appropriate diet education is needed for pregnant women so that they can consume
      adequate amounts of iron from food and supplements.

PMID- 23547878
TI  - Adding attenuation corrected images in myocardial perfusion imaging reduces the
      need for a rest study.
AB  - BACKGROUND: The American Society of Nuclear Cardiology and the Society of Nuclear
      Medicine conclude that incorporation of attenuation corrected (AC) images in
      myocardial perfusion scintigraphy (MPS) will improve diagnostic accuracy. The aim
      was to investigate the value of adding AC stress-only images for the decision
      whether a rest study is necessary or not. METHODS: 1,261 patients admitted to
      (99m)Tc MPS were studied. The stress studies were interpreted by two physicians
      who judged each study as "no rest study necessary" or "rest study necessary", by
      evaluating NC stress-only and NC + AC stress-only images. When there was
      disagreement between the two physicians, a third physician evaluated the studies.
      Thus, agreement between 2 out of 3 physicians was evaluated. RESULTS: The
      physicians assessed 214 more NC + AC images than NC images as "no rest study
      necessary" (17% of the study population). The number of no-rest-study-required
      was significantly higher for NC + AC studies compared to NC studies (859 vs 645
      cases (p < 0.0001). In the final report according to clinical routine, ischemia
      or infarction was reported in 23 patients, assessed as "no rest study necessary"
      (22 NC + AC cases; 8 NC cases), (no statistically significant difference). In 11
      of these, the final report stated "suspected/possible ischemia or infarction in a
      small area". CONCLUSIONS: Adding AC stress-only images to NC stress-only images
      reduce the number of unnecessary rest studies substantially.

PMID- 23547879
TI  - Metal and H2O2 free aerobic oxidative aromatic halogenation with [RNH3(+)] [NO3(
      )]/HX and [BMIM(SO3H)][NO3)x(X)y] (X = Br, Cl) as multifunctional ionic liquids.
AB  - Novel multifunctional ionic liquids (ILs) are generated by addition of HBr or HCl
      to alkylammonium nitrates ([RNH3(+)] [NO3(-)]) and to 3-methyl-1-(butyl-4
      sulfonyl)imidazolium nitrate ([BMIM(SO3H)][NO3]). The resulting [RNH3(+)] [NO3(
      )]/HX and mono (3-methyl-1-(butyl-4-sulfonyl)imidazolium) monohalogenide
      mononitrate ([BMIM(SO3H)][NO3)x(X)y] (X = Br, Cl)) systems act as solvent and
      promoter for aerobic oxidative halogenation of arenes under mild conditions in
      high yields that can be repeated over several cycles.

PMID- 23547880
TI  - Antifungal agent susceptibilities and interpretation of Malassezia pachydermatis
      and Candida parapsilosis isolated from dogs with and without seborrheic
      dermatitis skin.
AB  - Malassezia pachydermatis and Candida parapsilosis are recognized as commensal
      yeasts on the skin of healthy dogs but also causative agents of eborrheic
      dermatitis, especially in atopic dogs. We determined and compared the
      susceptibility levels of yeasts isolated from dogs with and without seborrheic
      dermatitis (SD) using the disk diffusion method (DD) for itraconazole (ITZ),
      ketoconazole (KTZ), nystatin (NYS), terbinafine (TERB) and 5-fluorocytosine (5
      FC) and the broth microdilution method (BMD) for ITZ and KTZ. The reliability
      between the methods was assessed using an agreement analysis and linear
      regression. Forty-five M. pachydermatis and 28 C. parapsilosis isolates were
      identified based on physiological characteristics and an approved molecular
      analysis. By DD, all tested M. pachydermatis isolates were susceptible to ITZ,
      KTZ, NYS and TERB but resistant to 5-FC. Only 46 - 60% of the tested C.
      parapsilosis isolates were susceptible to KTZ, TERB and 5-FC, but ITZ and NYS
      were effective against all. By BMD, over 95% of M. pachydermatis isolates were
      susceptible to KTZ and ITZ with an MIC90 < 0.03 and 0.12 MUg/ml, respectively.
      The frequency of KTZ- and ITZ-resistant C. parapsilosis was 29% and 7%, and the
      MIC90 values were 1 MUg/ml and 0.5-1 MUg/ml, respectively. Regarding the
      agreement analysis, 2.2% of minor errors were observed in M. pachydermatis and
      0.2-1% of very major errors occurred among C. parapsilosis. There were no
      significant differences in the yeast resistance rates between dogs with and
      without SD. KTZ and ITZ were still efficacious for M. pachydermatis but a high
      rate of KTZ resistant was reported in C. parapsilosis.

PMID- 23547882
TI  - Fluconazole treatment hyperpolarizes the plasma membrane of Candida cells.
AB  - Five pathogenic Candida species were compared in terms of their osmotolerance,
      tolerance to toxic sodium and lithium cations, and resistance to fluconazole. The
      species not only differed, in general, in their tolerance to high osmotic
      pressure (C. albicans and C. parapsilosis being the most osmotolerant) but
      exhibited distinct sensitivities to toxic sodium and lithium cations, with C.
      parapsilosis and C. tropicalis being very tolerant but C. krusei and C.
      dubliniensis sensitive to LiCl. The treatment of both fluconazole-susceptible (C.
      albicans and C. parapsilosis) and fluconazole-resistant (C. dubliniensis, C.
      krusei and C. tropicalis) growing cells with subinhibitory concentrations of
      fluconazole resulted in substantially elevated intracellular Na(+) levels. Using
      a diS-C3(3) assay, for the first time, to monitor the relative membrane potential
      (DeltaPsi) of Candida cells, we show that the fluconazole treatment of growing
      cells of all five species results in a substantial hyperpolarization of their
      plasma membranes, which is responsible for an increased non-specific transport of
      toxic alkali metal cations and other cationic drugs (e.g., hygromycin B). Thus,
      the combination of relatively low doses of fluconazole and drugs, whose import
      into the tested Candida strains is driven by the cell membrane potential, might
      be especially potent in terms of its ability to inhibit the growth of or even
      kill various Candida species.

PMID- 23547881
TI  - Disseminated histoplasmosis in an apparently immunocompetent individual from
      north India: a case report and review.
AB  - Mucocutaneous histoplasmosis is frequently reported in patients with acquired
      immune deficiency syndrome (AIDS), but it is rare in immunocompetent hosts.
      Disseminated histoplasmosis involving skin and larynx in a 50-year-old
      immunocompetent male is described from a non-endemic area in India. The infection
      appeared to be imported from Thailand. The patient responded very well to
      intravenous amphotericin B followed by itraconazole. A review of all cases of
      histoplasmosis occurring in immunocompetent patients from India is reported. Most
      cases are reported from the Gangetic plains. Adrenals are the most common organ
      involved in immunocompetent patients, but adrenal insufficiency is not common.
      Skin lesions and oral ulcers are seen in more than one-third of patients.
      Predisposing factors like exposure to birds, farming, mining, diabetes were
      observed in few patients.

PMID- 23547883
TI  - Functional mapping of PilF and PilQ in the Pseudomonas aeruginosa type IV pilus
      system.
AB  - Pseudomonas aeruginosa uses type IV pili (T4P) to interact with the environment
      and as key virulence factors when acting as an opportunistic pathogen. Assembly
      of the outer membrane PilQ secretin channel through which the pili are extruded
      is essential for pilus biogenesis. The P. aeruginosa T4P pilotin, PilF, is
      required for PilQ outer membrane localization and assembly into secretins and
      contains six tetratricopeptide (TPR) protein-protein interaction motifs,
      suggesting that the two proteins interact. In this study, we found that the first
      four TPR motifs of PilF are sufficient for PilQ outer membrane targeting,
      oligomerization, and function. Guided by our structure of PilF, site-directed
      mutagenesis of the protein surface revealed that a hydrophobic groove on the
      first TPR is required for PilF-mediated PilQ assembly. Deletion of individual
      domains within PilQ suggests that the N0, KH-like, or secretin domain, but not
      the C-terminus, interacts with PilF. Purified PilQ was found to pull down PilF
      from Pseudomonas cell lysates. Together, these data allow us to propose a model
      for PilF function in the T4P system. PilF interacts directly or indirectly with
      the PilQ monomer after translocation of both proteins through the inner membrane
      and acts as a co-chaperone with the Lol system to facilitate transit across the
      periplasm to the outer membrane. The mechanism of PilQ insertion and assembly,
      which appears to be independent of the Bam system, remains to be determined.

PMID- 23547884
TI  - Polycyclic hybrid isoprenoids from a reed rhizosphere soil derived Streptomyces
      sp. CHQ-64.
AB  - Two new hybrid isoprenoids, named indotertine B (2) and drimentine H (3), along
      with the known analogue drimentine C (4), were isolated from the reed rhizosphere
      soil derived actinomycete Streptomyces sp. CHQ-64. The structures of these
      compounds, including absolute configurations, were elucidated by extensive NMR,
      MS, and CD analyses. Indotertine B (2) exists as a pair of rotamers about the N
      C(O) bond with a 2:1 ratio and displays activities against HCT-8 and A549 tumor
      cell lines with IC50 values of 6.96 and 4.88 MUM, respectively. 

PMID- 23547885
TI  - Synthetic ion transporters that work with anion-pi interactions, halogen bonds,
      and anion-macrodipole interactions.
AB  - The transport of ions and molecules across lipid bilayer membranes connects cells
      and cellular compartments with their environment. This biological process is
      central to a host of functions including signal transduction in neurons and the
      olfactory and gustatory sensing systems, the translocation of biosynthetic
      intermediates and products, and the uptake of nutrients, drugs, and probes.
      Biological transport systems are highly regulated and selectively respond to a
      broad range of physical and chemical stimulation. A large percentage of today's
      drugs and many antimicrobial or antifungal agents take advantage of these
      systems. Other biological transport systems are highly toxic, such as the anthrax
      toxin or melittin from bee venom. For more than three decades, organic and
      supramolecular chemists have been interested in developing new transport systems.
      Over time, curiosity about the basic design has evolved toward developing of
      responsive systems with applications in materials sciences and medicine. Our
      early contributions to this field focused on the introduction of new structural
      motifs with emphasis on rigid-rod scaffolds, artificial beta-barrels, or pi
      stacks. Using these scaffolds, we have constructed selective systems that respond
      to voltage, pH, ligands, inhibitors, or light (multifunctional photosystems). We
      have described sensing applications that cover the three primary principles of
      sensor development: immunosensors that use aptamers, biosensors (an "artificial"
      tongue), and differential sensors (an "artificial" nose). In this Account, we
      focus on our recent interest in applying synthetic transport systems as
      analytical tools to identify the functional relevance of less common noncovalent
      interactions, anion-pi interactions, halogen bonds, and anion-macrodipole
      interactions. Anion-pi interactions, the poorly explored counterpart of cation-pi
      interactions, occur in aromatic systems with a positive quadrupole moment, such
      as TNT or hexafluorobenzene. To observe these elusive interactions in action, we
      synthesized naphthalenediimide transporters of increasing pi-acidity up to an
      unprecedented quadrupole moment of +39 Buckinghams and characterized these
      systems in comparison with tandem mass spectrometry and computational
      simulations. With pi-acidic calixarenes and calixpyrroles, we have validated our
      results on anion-pi interactions and initiated our studies of halogen bonds.
      Halogen bonds originate from the sigma-hole that appears on top of electron
      deficient iodines, bromines, and chlorines. Halogen-bond donors are ideal for
      anion transport because they are as strong and at least as directional as
      hydrogen-bond donors, but also hydrophobic. The discovery of the smallest
      possible organic anion transporter, trifluoroiodomethane, illustrates the power
      of halogen-bond donors. This molecule contains a single carbon atom and is a gas
      with a boiling point of -22  degrees C. Anion-macrodipole interactions, finally,
      differ significantly from anion-pi interactions and halogen bonds because they
      are important in nature and cannot be studied with small molecules. We have used
      anion-transporting peptide/urea nanotubes to examine these interactions in
      synthetic transport systems. To facilitate the understanding of the described
      results, we also include an in-depth discussion of the meaning of Hill
      coefficients. The use of synthetic transport systems to catch less common
      noncovalent interactions at work is important because it helps to expand the
      collection of interactions available to create functional systems. Progress in
      this direction furthers fundamental knowledge and invites many different
      applications. For illustration, we briefly discuss how this knowledge could apply
      to the development of new catalysts. 

PMID- 23547886
TI  - Using a double-plicated posterior leaflet as an anchor for mitral valve
      replacement: a case of mitral annular calcification.
AB  - We present a 62-year-old man with mitral regurgitation whose posterior annulus
      had severe calcification. Mitral valve replacement was performed by anchoring the
      cuff on a double-plicated posterior leaflet, and reinforcing with an equine
      pericardium. The patient is doing well 13 years after surgery with
      echocardiography showing no problems.

PMID- 23547887
TI  - Z-Selective ethenolysis with a ruthenium metathesis catalyst: experiment and
      theory.
AB  - The Z-selective ethenolysis activity of chelated ruthenium metathesis catalysts
      was investigated with experiment and theory. A five-membered chelated catalyst
      that was successfully employed in Z-selective cross metathesis reactions has now
      been found to be highly active for Z-selective ethenolysis at low ethylene
      pressures, while tolerating a wide variety of functional groups. This phenomenon
      also affects its activity in cross metathesis reactions and prohibits crossover
      reactions of internal olefins via trisubstituted ruthenacyclobutane
      intermediates. In contrast, a related catalyst containing a six-membered chelated
      architecture is not active for ethenolysis and seems to react through different
      pathways more reminiscent of previous generations of ruthenium catalysts.
      Computational investigations of the effects of substitution on relevant
      transition states and ruthenacyclobutane intermediates revealed that the
      differences of activities are attributed to the steric repulsions of the anionic
      ligand with the chelating groups.

PMID- 23547888
TI  - Higher n3-fatty acid status is associated with lower risk of iron depletion among
      food insecure Canadian Inuit women.
AB  - BACKGROUND: High rates of iron deficiency and anemia are common among Inuit and
      Arctic women despite a traditional diet based on animal source foods. However,
      representative data on iron status and relevant determinants for this population
      are lacking. The objectives were to determine the prevalence of anemia and
      depletion of iron stores, then to identify correlates of iron status in non
      pregnant Canadian Inuit women. METHODS: In a cross-sectional survey of 1550 women
      in the International Polar Year Inuit Health Survey, 2007-2008, hemoglobin, serum
      ferritin, soluble transferrin receptor (on a subset), C-reactive protein (CRP),
      RBC fatty acid composition, and H pylori serology were analyzed on fasting venous
      blood. Sociodemographic, food security status, anthropometric, dietary, and
      health data were collected. Correlates of iron status were assessed with
      multivariate linear and logistic models. RESULTS: Anemia was observed in 21.7%
      and iron deficient erythropoiesis in 3.3% of women. For women with CRP <= 10 mg/L
      (n = 1260) 29.4% had depleted iron stores. Inadequate iron intakes were observed
      in 16% of premenopausal and <1% of postmenopausal women. Among food insecure
      women, higher long-chain (n-3) polyunsaturated fatty acid (LC-PUFA) status, which
      reflects a more traditional food pattern, was associated with reduced risk of
      iron depletion. CONCLUSIONS: Iron depletion and anemia are a concern for Inuit
      women despite adequate total dietary iron intake primarily from heme sources. The
      high prevalence of H. pylori exposure, together with dietary iron adequacy,
      suggests an inflammation-driven iron deficiency and mild anemia. The anti
      inflammatory properties of LC-PUFA may be important for iron status in this
      population.

PMID- 23547889
TI  - Protective effect of allograft inflammatory factor-1 on the apoptosis of
      fibroblast-like synoviocytes in patients with rheumatic arthritis induced by
      nitro oxide donor sodium nitroprusside.
AB  - OBJECTIVES: Inadequate apoptosis of rheumatic arthritis (RA) fibroblast-like
      synoviocytes (FLS) plays a crucial role in the immunopathogenesis of RA.
      Allograft inflammatory factor-1 (AIF-1) is a novel member of the cytokine network
      that has been found to be involved in the immunological process underlying RA.
      This study was undertaken to investigate the potential effects of AIF-1 on nitric
      oxide donor (NO) sodium nitroprusside (SNP)-induced RA-FLS apoptosis, and the
      possible molecular mechanisms underlying these effects. METHOD: FLS obtained from
      patients with active RA were cultured in vitro and treated with SNP in the
      present or absence of AIF-1. RA-FLS viability was tested by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. RA-FLS
      apoptosis was analysed by flow cytometry and terminal dUTP nick-end labeling
      (TUNEL). The levels of phospho-Akt (p-Akt) and phospho-BAD (p-BAD) protein were
      detected by Western blot. RESULTS: A 24-h AIF-1 pretreatment at concentrations
      ranging from 10 to 100 ng/mL increased the viability of RA-FLS and prevented RA
      FLS apoptosis in a dose-dependent manner in the presence of SNP. AIF-1 induced
      phosphorylation of Akt and BAD in a time- and concentration-dependent manner. The
      effect was reversed by treatment with the PI3K inhibitor LY2940042 (LY) and the
      nuclear factor kappa B (NF-kappaB) inhibitor pyrrolidine dithiocarbamate (PDTC).
      CONCLUSIONS: AIF-1 can protect RA-FLS from apoptosis induced by NO by
      upregulating the expression of p-Akt and p-BAD.

PMID- 23547890
TI  - Religiosity, religious affiliation, and patterns of sexual activity and
      contraceptive use in France.
AB  - OBJECTIVE: To examine the association between religiosity and sexual and
      contraceptive behaviours in France. METHODS: Data were drawn from the 2005 Health
      Barometer survey, a random sample of 7495 women and 5634 men aged 15 to 44. We
      used logistic regression models to study the associations between religiosity and
      sexual and contraceptive behaviours, by gender and religious denomination.
      RESULTS: Three quarters of respondents (73%) reported no religious practice, 20%
      practised occasionally, and 7% regularly. Regular practice was associated with
      later sexual debut, regardless of religious denomination. Among participants less
      than 30 years old, religious respondents were less likely to have used a condom
      at first sexual intercourse (odds ratio [OR] = 0.2 for women, OR = 0.4 for men)
      or any form of contraception (OR = 0.2 for women). At the time of the survey,
      sexually experienced adolescents who reported regular religious practice were
      less likely to use contraception (84.7% vs. 98.1%, p < 0.001). Regular practice
      was associated with a 50% decrease in the odds of using very effective methods
      for Catholics, but had no effect among Muslims. CONCLUSION: This study, conducted
      in the French secularised context, shows a complex relationship between
      religiosity and sexual behaviours, which varies by gender, religious affiliation
      and during the life course.

PMID- 23547891
TI  - Cation bridging studied by specular neutron reflection.
AB  - The binding of an anionic surfactant onto an anionic surface by addition of
      divalent ions is reported based on experimental data from specular neutron
      reflection (NR) and attenuated total internal reflection IR spectroscopy (ATR
      IR). Similar measurements using monovalent ions (sodium) do not show any evidence
      of such adsorption, even though the amount of surfactant can be much higher. This
      data is interpreted in terms of the so-called bridging mechanism of ion binding.

PMID- 23547892
TI  - Unusual case of coexisting cerebellopontine epidermoid and neurenteric cyst.

PMID- 23547893
TI  - Posterior third ventricular mature teratoma with a hemangiomatous component.

PMID- 23547894
TI  - Rosette-forming glioneuronal tumor of the cerebellum in statu nascendi: an
      incidentally detected diminutive example indicates derivation from the internal
      granule cell layer.
AB  - Rosette-forming glioneuronal tumor (RGNT) is a recently introduced, indolent
      neoplasm composed of diminutive circular aggregates of neurocytic-like cells on a
      noninfiltrative astrocytic background, typically located in the cerebellar
      midline The traded concept of RGNT being derived from site-specific
      periventricular precursors may be questioned in the face of extracerebellar
      examples as well as ones occurring in combination with other representatives of
      the glioneuronal family. We describe a hitherto not documented example of
      asymptomatic RGNT discovered during autopsy of a 74-year-old male. Located in the
      tuberal vermis, this lesion of 6 mm diameter consisted of several microscopic
      nests of what were felt to represent nascent stages of RGNT, all of them centered
      on the internal granular layer, and ranging from mucoid dehiscences thereof to
      fully evolved - if small - tumor foci. Molecular genetic analysis revealed a
      missense mutation in Exon 20 of the PIK3CA gene involving an A->G transition at
      Nucleotide 3140. On the other hand, neither codeletion of chromosomes 1p/19q nor
      pathogenic mutations of IDH1/2 were detected. By analogy with in situ paradigms
      in other organs, we propose that this tumor is likely to have arisen from the
      internal granular layer, rather than the plate of the 4th ventricle. A suggestive
      departure from the wholesale argument of "undifferentiated precursors", this
      finding also indirectly indicates that a subset of non-classical RGNTs - in
      particular extracerebellar examples, whose origin cannot be mechanistically
      accounted for by either of the above structures - may possibly reflect an
      instance of phenotypic convergence, rather than a lineage-restricted entity. 

PMID- 23547895
TI  - Presence of alternative lengthening of telomeres associated circular
      extrachromosome telomere repeats in primary leukemia cells of chronic myeloid
      leukemia.
AB  - BACKGROUND: The predominant mechanism by which human tumors maintain telomere
      length is via telomerase. In ~10% of tumor samples, however, telomere length is
      conserved, despite no detectable telomerase activity, in part through activation
      of the alternative lengthening of telomeres (ALT) pathway. METHODS: We studied
      the circular extra-chromosomal telomeric repeat (ECTR), an ALT hallmark, and
      telomerase activity in 24 chronic myeloid leukemia (CML) patients in chronic
      phase (CP). RESULTS: We identified the presence of ECTR in primary leukemia cells
      from some of these samples, which indicates the possible involvement of an ALT
      mechanism. Moreover, we found that some samples exhibited both circular ECTR and
      telomerase activities, suggesting that both mechanisms can contribute to the
      onset of CML. CONCLUSION: We propose that ALT or the combined activities of ALT
      and telomerase might be required for the early stages of leukemogenesis. These
      findings shed new light into the oncogenic pathways responsible for the
      maintenance of telomere length in leukemia, which will ultimately determine the
      effectiveness of anti-telomerase-based treatment protocols.

PMID- 23547897
TI  - RegTransBase--a database of regulatory sequences and interactions based on
      literature: a resource for investigating transcriptional regulation in
      prokaryotes.
AB  - BACKGROUND: Due to the constantly growing number of sequenced microbial genomes,
      comparative genomics has been playing a major role in the investigation of
      regulatory interactions in bacteria. Regulon inference mostly remains a field of
      semi-manual examination since absence of a knowledgebase and informatics platform
      for automated and systematic investigation restricts opportunities for
      computational prediction. Additionally, confirming computationally inferred
      regulons by experimental data is critically important. DESCRIPTION: RegTransBase
      is an open-access platform with a user-friendly web interface publicly available
      at http://regtransbase.lbl.gov. It consists of two databases - a manually
      collected hierarchical regulatory interactions database based on more than 7000
      scientific papers which can serve as a knowledgebase for verification of
      predictions, and a large set of curated by experts transcription factor binding
      sites used in regulon inference by a variety of tools. RegTransBase captures the
      knowledge from published scientific literature using controlled vocabularies and
      contains various types of experimental data, such as: the activation or
      repression of transcription by an identified direct regulator; determination of
      the transcriptional regulatory function of a protein (or RNA) directly binding to
      DNA or RNA; mapping of binding sites for a regulatory protein; characterization
      of regulatory mutations. Analysis of the data collected from literature resulted
      in the creation of Putative Regulons from Experimental Data that are also
      available in RegTransBase. CONCLUSIONS: RegTransBase is a powerful user-friendly
      platform for the investigation of regulation in prokaryotes. It uses a collection
      of validated regulatory sequences that can be easily extracted and used to infer
      regulatory interactions by comparative genomics techniques thus assisting
      researchers in the interpretation of transcriptional regulation data.

PMID- 23547896
TI  - Body mass index and incident coronary heart disease in women: a population-based
      prospective study.
AB  - BACKGROUND: A high body mass index (BMI) is associated with an increased risk of
      mortality from coronary heart disease (CHD); however, a low BMI may also be
      associated with an increased mortality risk. There is limited information on the
      relation of incident CHD risk across a wide range of BMI, particularly in women.
      We examined the relation between BMI and incident CHD overall and across
      different risk factors of the disease in the Million Women Study. METHODS: 1.2
      million women (mean age=56 years) participants without heart disease, stroke, or
      cancer (except non-melanoma skin cancer) at baseline (1996 to 2001) were followed
      prospectively for 9 years on average. Adjusted relative risks and 20-year
      cumulative incidence from age 55 to 74 years were calculated for CHD using Cox
      regression. RESULTS: After excluding the first 4 years of follow-up, we found
      that 32,465 women had a first coronary event (hospitalization or death) during
      follow-up. The adjusted relative risk for incident CHD per 5 kg/m2 increase in
      BMI was 1.23 (95% confidence interval (CI) 1.22 to 1.25). The cumulative
      incidence of CHD from age 55 to 74 years increased progressively with BMI, from 1
      in 11 (95% CI 1 in 10 to 12) for BMI of 20 kg/m2, to 1 in 6(95% CI 1 in 5 to 7)
      for BMI of 34 kg/m2. A 10 kg/m2 increase in BMI conferred a similar risk to a 5
      year increment in chronological age. The 20 year cumulative incidence increased
      with BMI in smokers and non-smokers, alcohol drinkers and non-drinkers,
      physically active and inactive, and in the upper and lower socioeconomic classes.
      In contrast to incident disease, the relation between BMI and CHD mortality
      (n=2,431) was J-shaped. For the less than 20 kg/m2 and >=35 kg/m2 BMI categories,
      the respective relative risks were 1.27 (95% CI 1.06 to 1.53) and 2.84 (95% CI
      2.51 to 3.21) for CHD deaths, and 0.89 (95% CI 0.83 to 0.94) and 1.85 (95% CI
      1.78 to 1.92) for incident CHD. CONCLUSIONS: CHD incidence in women increases
      progressively with BMI, an association consistently seen in different subgroups.
      The shape of the relation with BMI differs for incident and fatal disease.

PMID- 23547898
TI  - Tracheal stenting for primary tracheal mucosa-associated lymphoid tissue
      lymphoma.
AB  - Primary tracheal mucosa-associated lymphoid tissue (MALT) lymphoma is extremely
      rare. We report a 49-year-old female patient with the complaint of dyspnea.
      Fiberoptic bronchoscopy showed polypoid, variable-sized and irregular nodules
      causing narrowing of the tracheal lumen from the proximal trachea to the left
      main bronchus. Because of severe stenosis in the airway and the severity of
      symptoms, this case was unresectable. The patient was then treated successfully
      with placement of an endobronchial stent through bronchofibroscopy. After the
      placement of the stent, bronchoscopic biopsy was performed. Pathological analysis
      confirms a diagnosis of MALT-associated malignant lymphoma. We performed systemic
      chemotherapy on the patient. The temporary stent was removed after the reduction
      of the stenosis. This is the first case in which tracheal MALT lymphoma was
      treated successfully following tracheal stent insertion guided by
      bronchofibroscopy. Temporary tracheal stenting can be a favorable choice for a
      patient with tracheal stenosis caused by primary tracheal MALT lymphoma.

PMID- 23547900
TI  - "Can community level interventions have an impact on equity and utilization of
      maternal health care" - evidence from rural Bangladesh.
AB  - BACKGROUND: Evidence from low and middle income countries (LMICs) suggests that
      maternal mortality is more prevalent among the poor whereas access to maternal
      health services is concentrated among the rich. In Bangladesh substantial
      inequities exist both in the use of facility-based basic obstetric care and for
      home births attended by skilled birth attendant. BRAC initiated an intervention
      on Improving Maternal, Neonatal, and Child Survival (IMNCS) in the rural areas of
      Bangladesh in 2008. One of the objectives of the intervention is to improve the
      utilization of maternal and child health care services among the poor. This study
      aimed to look at the impact of the intervention on utilization and also on equity
      of access to maternal health services. METHODS: A quasi-experimental pre-post
      comparison study was conducted in rural areas of five districts comprising three
      intervention (Gaibandha, Rangpur and Mymensingh) and two comparison districts
      (Netrokona and Naogaon). Data on health seeking behaviour for maternal health
      were collected from a repeated cross sectional household survey conducted in 2008
      and 2010. RESULTS: Results show that the intervention appears to cause an
      increase in the utilization of antenatal care. The concentration index (CI) shows
      that this has become pro-poor over time (from CI: 0.30 to CI: 0.04) in the
      intervention areas. In contrast the use of ANC from medically trained providers
      has become pro-rich (from, CI: 0.18 to CI: 0.22). There was a significant
      increase in the utilisation of trained attendants for home delivery in the
      intervention areas compared to the comparison areas and the change was found to
      be pro-poor. Use of postnatal care cervices was also found to be pro-poor (from
      CI: 0.37 to CI: 0.14). Utilization of ANC services provided by medically trained
      provider did not improve in the intervention area. However, where the
      intervention had a positive effect on utilization it also seemed to have had a
      positive effect on equity. CONCLUSIONS: To sustain equity in health care
      utilization, the IMNCS programme needs to continue providing free home based
      services. In addition to this, the programme should also continue to provide
      funding to bear the cost to those mothers who are not able to have the
      comprehensive ANC from medically trained providers.

PMID- 23547902
TI  - Drastic reduction of piperacillin-tazobactam concentrations in an in-vitro model
      of continuous venovenous hemofiltration: proposal of an innovative modality of
      administration to maintain them at constant concentration.
AB  - BACKGROUND/AIMS: Critically-ill patients often undergo continuous renal
      replacement therapy (CRRT) and need antimicrobial therapy. Piperacillin and
      tazobactam (Pip-Tzb) are cleared by CRRT. Our aim is to evaluate Pip-Tzb removal
      in an in-vitro-single-pool-model of continuous-veno-venous-hemofiltration (CVVH);
      we test a new method of Pip-Tzb administration during CRRT assuring constant
      levels of concentrations above the minimum inhibitory concentration (MIC).
      METHODS: In an in-vitro-single-pool-model of CVVH, two solutions (Protein-Free
      Solution, PFS and Fresh-Frozen- Plasma, FFP) added with Pip-Tzb were tested for
      Pip-Tzb removal and adsorption. Then, to keep concentrations constantly above the
      MIC during CVVH, we add Pip-Tzb in the reinfusion bags. RESULTS: Pip-Tzb rapidly
      decreased than the MIC during CVVH. The adsorption was irrelevant in the test
      with FPS. Adding Pip-Tzb in the reinfusion bags of the CVVH system, we observed
      constant concentrations of Pip-Tzb over time. CONCLUSION: The association of Pip
      Tzb is rapidly cleared with a real risk of inadequate dosages in patients
      undergoing CRRT. Adding Pip-Tzb in the reinfusion bags above the MIC, we obtained
      stability of concentrations during CVVH.

PMID- 23547903
TI  - Cardioprotective effect of resveratrol and resveratroloside.
AB  - Cardioprotective effect of resveratrol and resveratroloside was determined in
      ischemia-reperfusion experiments on rats. It was found that single
      intraperitoneal administration of any compound (10 mg/kg) followed by 30-min
      ischemia and 120-min reperfusion resulted in statistically significant decrease
      of myocardial infarct area (55.0+/-4.0% for control group; 40.7+/-4.4% for the
      group 1 received resveratrol; 41.6+/-4.8% for the group 2 received
      resveratroloside). The cardioprotective effect of resveratroloside was detected
      for the first time. 

PMID- 23547904
TI  - Studies toward the biomimetic total synthesis of (-)-PF-1018.
AB  - Pericyclic reaction cascades are unparalleled in their ability to quickly
      generate complex structures with excellent stereocontrol. Herein, the use of a
      biomimetic Stille/8pi electrocyclization/Diels-Alder cascade to successfully
      assemble the core structure of (-)-PF-1018 is reported.

PMID- 23547905
TI  - In vitro translocation experiments with RxLR-reporter fusion proteins of Avr1b
      from Phytophthora sojae and AVR3a from Phytophthora infestans fail to demonstrate
      specific autonomous uptake in plant and animal cells.
AB  - Plant-pathogenic oomycetes have a large set of secreted effectors that can be
      translocated into their host cells during infection. One group of these effectors
      are the RxLR effectors for which it has been shown, in a few cases, that the RxLR
      motif is important for their translocation. It has been suggested that the RxLR
      leader sequences alone are enough to translocate the respective effectors into
      eukaryotic cells through binding to surface-exposed phosphoinositol-3-phosphate.
      These conclusions were primary based on translocation experiments conducted with
      recombinant fusion proteins whereby the RxLR leader of RxLR effectors (i.e.,
      Avr1b from Phytophthora sojae) were fused to the green fluorescent protein
      reporter-protein. However, we failed to observe specific cellular uptake for a
      comparable fusion protein where the RxLR leader of the P. infestans AVR3a was
      fused to monomeric red fluorescent protein. Therefore, we reexamined the ability
      of the reported P. sojae AVR1b RxLR leader to enter eukaryotic cells. Different
      relevant experiments were performed in three independent laboratories, using
      fluorescent reporter fusion constructs of AVR3a and Avr1b proteins in a side-by
      side comparative study on plant tissue and human and animal cells. We report that
      we were unable to obtain conclusive evidence for specific RxLR-mediated
      translocation.

PMID- 23547906
TI  - The dar genes of Pseudomonas chlororaphis PCL1606 are crucial for biocontrol
      activity via production of the antifungal compound 2-hexyl, 5-propyl resorcinol.
AB  - To determine the genetic basis by which 2-hexyl, 5-propyl resorcinol (HPR) is
      produced by the biocontrol rhizobacterium Pseudomonas chlororaphis (formerly
      known as P. fluorescens) PCL1606, the presence and role of dar genes were
      investigated. To accomplish this aim, the pCGNOV-1 plasmid was isolated from a
      PCL1606 genomic library and was shown to hybridize to various dar probes by
      Southern blot. An analysis of the pCGNOV-1 genomic DNA revealed the presence of
      five open reading frames that were homologous to dar genes and had an
      organization that resembled the arrangement of previously described P.
      chlororaphis strains. Phylogenetic studies resulted in the clustering of PCL1606
      with the P. chlororaphis subgroup, which supported the renaming of this strain
      from P. fluorescens to P. chlororaphis PCL1606. The construction of insertional
      mutants for each homologous dar gene in P. chlororaphis PCL1606 along with their
      corresponding complemented derivative strains restored HPR production and
      confirmed the key role of the dar A and darB genes in HPR production and in the
      antagonistic phenotype. Finally, biocontrol assays were performed on avocado
      Rosellinia and tomato-Fusarium test systems using the HPR-defective and 
      complemented derivative strains generated here and demonstrated the crucial role
      of the biosynthetic dar genes in the biocontrol phenotype of P. chlororaphis
      PCL1606. This biocontrol phenotype is dependent on the dar genes via their
      production of the HPR antibiotic. Some of the dar genes not directly involved in
      the biosynthesis of HPR, such as darS or darR, might contribute to regulatory
      features of HPR production.

PMID- 23547907
TI  - Trialkyl phosphites and diaryliodonium salts as co-initiators in a system for
      radical-promoted visible-light-induced cationic polymerization.
AB  - Trialkyl phosphites ((RO)3P) can act as co-initiators for the diaryliodonium
      induced cationic polymerization of cyclohexene oxide (CHO) or THF. A radical
      initiation step is also required, consistent with the essential role of a radical
      chain reaction of the phosphite with the iodonium salt to form polymerization
      starting aryltrialkoxyphosphonium salts (ArP(+)(OR)3). We used the visible
      photolysis of phenylazoisobutyronitrile (PAIBN) as the radical initiation step.
      The presence of multiple fluorine substituents on the phosphite, as in tris(2,2,2
      trifluoroethyl) phosphite (TFP), allows polymerization to proceed with a minimal
      amount of chain transfer from nucleophilic attack by the phosphite. In a typical
      experiment, a CHO solution of bis(4-tert-butylphenyl)iodonium hexafluorophosphate
      (0.05 M), TFP (0.1 M), and PAIBN (0.02 M) was illuminated with a 65-W compact
      fluorescent bulb for 1 h, resulting in a 78% conversion to poly(cyclohexene
      oxide) with an average molecular weight (MW) of 25000. We also used competition
      experiments to determine approximate rate constants for reactions of phenyl
      radicals with CHO (k = 2 * 10(6) M(-1) s(-1)) and with TFP (k = 2 * 10(8) M(-1)
      s(-1)).

PMID- 23547909
TI  - A hierarchy of static correlation models.
AB  - It is commonly accepted in the scientific literature that the static correlation
      energy, Estat, of a system can be defined as the exact correlation energy of its
      valence electrons in a minimal basis. Unfortunately, the computational cost of
      calculating the exact correlation energy within a fully optimized minimal basis
      grows exponentially with system size, making such calculations intractable for
      all but the smallest systems. However, analogous to single-reference methods, it
      is possible to systematically approximate both the treatment of electron
      correlation and flexibility of the minimal basis to reduce computational cost.
      This yields a hierarchy of methods for calculating Estat, ranging from coupled
      cluster methods in a minimal atomic basis up to full valence complete active
      space methods with a minimal molecular orbital basis constructed from a near
      complete atomic orbital basis. By examining a variety of dissociating diatomics,
      along with equilibrium and transition structures for polyatomic systems, we show
      that standard coupled cluster models with minimal atomic basis sets (e.g., STO
      3G) offer a convenient and cost-effective hierarchy of black box estimates for
      Estat in small- to medium-sized systems near their equilibrium geometries. To
      properly describe homolytic bond dissociation, it is better to use a more
      flexible basis set expansion so that each atomic orbital can effectively adapt to
      its molecular environment. 

PMID- 23547910
TI  - Emergency coronary artery bypass grafting using minimized versus standard
      extracorporeal circulation--a propensity score analysis.
AB  - BACKGROUND: The impact of minimized extracorporeal circulation (MECC) for
      emergency revascularization remains controversial. METHODS: A total of 348
      patients underwent emergency CABG with MECC (n=146) or conventional
      extracorporeal circulation (CECC; n=175) between January 2005 and December 2010.
      Using propensity score matching after binary logistic regression, 100 patients,
      who underwent CABG with MECC could be matched with 100 patients, who underwent
      CABG with CECC. Primary outcome was 30-day mortality. RESULTS: Unadjusted 30-day
      mortality was 14.8% in patients with CECC and 6.9% in those with MECC (mean
      difference -7.9%; p=0.03). The adjusted mean difference (average treatment effect
      of the treated, ATT) after matching was -1.0% (95% CI -8.6 to 7.6; p=1.0).
      Intensive care unit stay (adjusted mean difference 1.0; 95% CI -0.2 to 3.2;
      p=0.70) and hospital stay (adjusted mean difference 1.0; 95% CI -2.0 to 3.6;
      p=0.40) did not show significant differences between both groups. The adjusted
      mean difference for postoperative low cardiac output syndrome was -1.1% (95% CI 
      7.3 to 7.1; p=0.83) without significant differences between CECC and MECC.
      Postoperative mechanical ventilation time, drain loss, postoperative
      rethoracotomy, postoperative neurological events, new onset renal replacement
      therapy and respiratory failure also had insignificant average treatment effects
      of the treated. In addition, all average treatment effects (ATEs) did not
      significantly differ between both groups. CONCLUSION: Using propensity score
      estimation and matching, we did not observe significant differences in terms of
      survival and further outcomes in patients who undergo emergency CABG with CECC or
      MECC, but our results call for further analysis.

PMID- 23547908
TI  - Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle
      mitochondria.
AB  - Calcium is believed to regulate mitochondrial oxidative phosphorylation, thereby
      contributing to the maintenance of cellular energy homeostasis. Skeletal muscle,
      with an energy conversion dynamic range of up to 100-fold, is an extreme case for
      evaluating the cellular balance of ATP production and consumption. This study
      examined the role of Ca(2+) in the entire oxidative phosphorylation reaction
      network in isolated skeletal muscle mitochondria and attempted to extrapolate
      these results back to the muscle, in vivo. Kinetic analysis was conducted to
      evaluate the dose-response effect of Ca(2+) on the maximal velocity of oxidative
      phosphorylation (V(maxO)) and the ADP affinity. Force-flow analysis evaluated the
      interplay between energetic driving forces and flux to determine the conductance,
      or effective activity, of individual steps within oxidative phosphorylation.
      Measured driving forces [extramitochondrial phosphorylation potential
      (DeltaG(ATP)), membrane potential, and redox states of NADH and cytochromes b(H),
      b(L), c(1), c, and a,a(3)] were compared with flux (oxygen consumption) at 37 
      degrees C; 840 nM Ca(2+) generated an ~2-fold increase in V(maxO) with no change
      in ADP affinity (~43 MUM). Force-flow analysis revealed that Ca(2+) activation of
      V(maxO) was distributed throughout the oxidative phosphorylation reaction
      sequence. Specifically, Ca(2+) increased the conductance of Complex IV (2.3
      fold), Complexes I and III (2.2-fold), ATP production/transport (2.4-fold), and
      fuel transport/dehydrogenases (1.7-fold). These data support the notion that
      Ca(2+) activates the entire muscle oxidative phosphorylation cascade, while
      extrapolation of these data to the exercising muscle predicts a significant role
      of Ca(2+) in maintaining cellular energy homeostasis.

PMID- 23547911
TI  - Morbid obesity in women on the rise: an observational, population-based study.
AB  - BACKGROUND: The obesity epidemic is generally monitored by the proportion of the
      population whose body mass index (BMI) exceeds 30 kg/m2 but this masks the
      growing proportion of those who are morbidly obese. This issue is important as
      the adverse health risks amplify as the level of obesity increases. The aim of
      this study was to determine how the prevalence of morbid obesity (BMI  >=  40.0
      kg/m2) has changed over a decade among women living in south-eastern Australia.
      METHODS: BMI was determined for women in the Geelong Osteoporosis study (GOS)
      during two time periods, a decade apart. Height and weight were measured for
      1,494 women (aged 20-94 years) during 1993-7 and for 1,076 women (aged 20-93
      years), 2004-8, and the BMI calculated as weight in kilograms divided by the
      square of the height in metres (kg/m2). Prevalence estimates were age
      standardised to enable direct comparisons. RESULTS: Mean BMI increased from 26.0
      kg/m2 (95%CI 25.7-26.3) in 1993-7, to 27.1 kg/m2 (95%CI 26.8-27.4) in 2004-8.
      During this period, the prevalence of morbid obesity increased from 2.5% to 4.2%
      and the standardised morbidity ratio for morbid obesity was 1.69 (95%CI 1.26
      2.27). Increases in mean BMI and prevalence of morbid obesity were observed for
      all ages and across the socioeconomic spectrum. CONCLUSIONS: These findings
      reveal that over a decade, there has been an increase in mean BMI among women
      residing in south-eastern Australia, resulting in a measurable increase in the
      prevalence of morbid obesity.

PMID- 23547912
TI  - Quantum-dot-based photoelectrochemical sensors for chemical and biological
      detection.
AB  - Quantum-dot-based photoelectrochemical sensors are powerful alternatives for the
      detection of chemicals and biochemical molecules compared to other sensor types,
      which is the primary reason as to why they have become a hot topic in
      nanotechnology-related analytical methods. These sensors basically consist of QDs
      immobilized by a linking molecule (linker) to an electrode, so that upon their
      illumination, a photocurrent is generated which depends on the type and
      concentration of the respective analyte in the immediate environment of the
      electrode. The present review provides an overview of recent developments in the
      fabrication methods and sensing concepts concerning direct and indirect
      interactions of the analyte with quantum dot modified electrodes. Furthermore, it
      describes in detail the broad range of different sensing applications of such
      quantum-dot-based photoelectrochemical sensors for inorganic and organic (small
      and macro-) molecules that have arisen in recent years. Finally, a number of
      aspects concerning current challenges on the way to achieving real-life
      applications of QD-based photochemical sensing are addressed.

PMID- 23547913
TI  - Production of the alkaloid swainsonine by a fungal endosymbiont of the Ascomycete
      order Chaetothyriales in the host Ipomoea carnea.
AB  - Some plant species within the Convolvulaceae (morning glory family) from South
      America, Africa, and Australia cause a neurologic disease in grazing livestock
      caused by swainsonine. These convolvulaceous species including Ipomoea carnea
      contain the indolizidine alkaloid swainsonine, an inhibitor of alpha-mannosidase
      and mannosidase II, and polyhydroxy nortropane alkaloids, the calystegines which
      are glycosidase inhibitors. Swainsonine has been shown to be produced by a fungal
      endosymbiont in legumes of the Astragalus and Oxytropis genera, where it causes a
      similar neurologic disease in grazing livestock called locoism. Here we
      demonstrate that I. carnea plants are infected with a fungal endosymbiont that
      was cultured from its seeds and which produced swainsonine in pure culture but
      not the calystegines. The same fungal endosymbiont was detected by PCR and by
      culturing in I. carnea plants containing swainsonine. The fungal endosymbiont
      belongs to the Ascomycete order Chaetothyriales. Plants derived from fungicide
      treated seeds lacked swainsonine, but calystegine concentrations were unaltered. 

PMID- 23547914
TI  - Responsive hybrid microcapsules by the one-step interfacial thiol-ene
      photopolymerization.
AB  - We here demonstrated a general, convenient, and robust method to fabricate the
      hybrid microcapsules through the one-step thiol-ene photopolymerization at the
      interface between toluene and water. In the presence of amphiphilic polyhedral
      oligomeric silsesquioxane (POSS) containing thiol groups (PTPS) as reactive
      surfactants and trimethylolpropane triacrylate (TMPTA) as a cross-linker, the
      wall of hybrid microcapsules can be photo-cross-linked. The obtained hybrid
      microcapsules (HMCs) were well-characterized by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and
      confocal laser scanning microscopy (CLSM). The results revealed that the obtained
      HMCs are uniform with the tunable size in diameter (2-4 MUm) and wall thickness
      (55-120 nm). The size of HMCs increased with the increasing content of toluene.
      The wall thickness of HMCs decreased with the increasing content of toluene,
      while the wall thickness of HMCs increased with the increasing content of cross
      linker TMPTA. Furthermore, HMCs are thermoresponsive in aqueous solution, can
      encapsulate both hydrophobic and dydrophilic dyes, and can be used in the
      controlled dispersion of dyes in different mediums. It is believed that this
      simple, robust, and general method to fabricate the hybrid microcapsules will
      extend the potential application fields of microcapsules, such as in the
      controlled dispersion and drug delivery.

PMID- 23547915
TI  - Hyalomma scupense (Acari, Ixodidae) in northeast Tunisia: seasonal population
      dynamics of nymphs and adults on field cattle.
AB  - Hyalomma scupense is a two-host tick infesting mainly cattle representing in
      North Africa the vector of tropical theileriosis (Theileria annulata infection),
      a major tick-borne disease affecting cattle. Any effective control programme of
      ticks requires a good knowledge of the biology of the target species. In the
      present study, three cattle farms in northeast Tunisia were surveyed during the
      activity seasons for adult and nymphs of Hyalomma scupense. Several indicators
      were studied, including chronological indicators, infestation prevalence,
      infestation intensity and feeding predilection sites of the ticks. The adult
      ticks were present from mid-June to late November. Nymphs were observed on
      animals from early September to late November. A large proportion of the ticks
      were attached in the posterior udder quarters: 41% and 64% of adult ticks and
      nymphs, respectively. The animals that were heavily infested by adult ticks were
      also heavily infested by nymphs. Moreover, 17% of adult ticks and 53% of nymphs
      were present on only 5% of cattle population. These data are important for the
      success of targeted acaricide application leading to a dramatic decrease of
      acaricide quantity needed for the treatment. When the preferential sites of
      attachment are known, the effectiveness of manual removal of ticks can be
      improved. The presence of highly infested animals is to be considered when any
      control programme is implemented, since these animals harbour a high proportion
      of the ticks.

PMID- 23547916
TI  - The microstructure of practice activities engaged in by elite and recreational
      youth cricket players.
AB  - Practice plays an important role in skill acquisition, although not all practice
      is of equal quality. We examined the types of team practice activities in four
      groups of youth cricket players. The groups were recreational- and elite-children
      (9 to 12 years of age) and recreational- and elite-adolescent players (13 to 17
      years of age). Time motion analysis recorded the duration in two types of
      practice activities, namely, Training Form and Playing Form. Training Form is
      mainly drill-type activities, whereas Playing Form is mainly games-based
      activities. Training Form activity is thought to contain fewer opportunities to
      develop the perceptual, cognitive and motor skills required for successful
      performance in competition when compared to Playing Form. Session duration was a
      mean value of 95, s = 29 min. All players combined spent 69% of session time in
      Training Form activity and 19% in Playing Form, with the remaining percentage of
      time spent in transition between activities. Recreational-children spent around
      half of their time in Playing Form activity, whereas both elite and adolescent
      groups spent little or no time in this activity. Findings from this research
      highlight a gap between research and practice that may not be optimal for skill
      acquisition.

PMID- 23547917
TI  - The impact of body mass index on perioperative outcomes in robot-assisted
      laparoscopic partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: Obese patients undergoing surgical procedures are at
      increased risk for perioperative morbidity. The purpose of this study is to
      determine whether there is an association with body mass index (BMI),
      clinicopathologic features, and perioperative outcomes and complications in
      patients undergoing robot-assisted laparoscopic partial nephrectomy (RPN).
      PATIENTS AND METHODS: Medical records of 283 patients who underwent RPN between
      2007 and 2012 were reviewed from an Institutional Review Board approved database.
      We analyzed the association of perioperative outcomes and complications of the
      surgery with BMI and clinicopathologic features using analysis of variance,
      Kruskal-Wallis test, t test and chi-square-test. Eventually, independent factors
      associated with perioperative outcomes and complications were studied using
      univariate and multivariate regression analysis. RESULTS: Perioperative outcomes
      including estimated blood loss (EBL), length of hospital stay (LOS) and operative
      time (OT) were significantly associated with BMI (P=0.002, P=0.009 and P=0.002,
      respectively). Warm ischemia time (WIT), perioperative complications, and change
      in glomerular filtration rate (GFR) before and after surgery were not associated
      with BMI (P=0.459, P=0.86 and P=0.773). In multivariate analysis, BMI, tumor
      size>=4 cm, and collecting system invasion were independently associated with EBL
      and OT. Increased LOS was independently associated with BMI and tumor size >=4
      cm. CONCLUSIONS: Increasing BMI was not associated with a significant increase in
      perioperative complications, WIT, or change in GFR in patients undergoing RPN at
      a high-volume tertiary medical center. Collecting system invasion or tumor size
      >=4 cm and BMI were independently associated with higher EBL, LOS, and OT,
      however.

PMID- 23547918
TI  - Mitotic bookmarking by transcription factors.
AB  - Mitosis is accompanied by dramatic changes in chromatin organization and nuclear
      architecture. Transcription halts globally and most sequence-specific
      transcription factors and co-factors are ejected from mitotic chromatin. How then
      does the cell maintain its transcriptional identity throughout the cell division
      cycle? It has become clear that not all traces of active transcription and gene
      repression are erased within mitotic chromatin. Many histone modifications are
      stable or only partially diminished throughout mitosis. In addition, some
      sequence-specific DNA binding factors have emerged that remain bound to select
      sites within mitotic chromatin, raising the possibility that they function to
      transmit regulatory information through the transcriptionally silent mitotic
      phase, a concept that has been termed "mitotic bookmarking." Here we review
      recent approaches to studying potential bookmarking factors with regards to their
      mitotic partitioning, and summarize emerging ideas concerning the in vivo
      functions of mitotically bound nuclear factors.

PMID- 23547919
TI  - RNA sequencing reveals small RNAs differentially expressed between incipient
      Japanese threespine sticklebacks.
AB  - BACKGROUND: Non-coding small RNAs, ranging from 20 to 30 nucleotides in length,
      mediate the regulation of gene expression and play important roles in many
      biological processes. One class of small RNAs, microRNAs (miRNAs), are highly
      conserved across taxa and mediate the regulation of the chromatin state and the
      post-transcriptional regulation of messenger RNA (mRNA). Another class of small
      RNAs is the Piwi-interacting RNAs, which play important roles in the silencing of
      transposons and other functional genes. Although the biological functions of the
      different small RNAs have been elucidated in several laboratory animals, little
      is known regarding naturally occurring variation in small RNA transcriptomes
      among closely related species. RESULTS: We employed next-generation sequencing
      technology to compare the expression profiles of brain small RNAs between
      sympatric species of the Japanese threespine stickleback (Gasterosteus
      aculeatus). We identified several small RNAs that were differentially expressed
      between sympatric Pacific Ocean and Japan Sea sticklebacks. Potential targets of
      several small RNAs were identified as repetitive sequences. Female-biased miRNA
      expression from the old X chromosome was also observed, and it was attributed to
      the degeneration of the Y chromosome. CONCLUSIONS: Our results suggest that
      expression patterns of small RNA can differ between incipient species and may be
      a potential mechanism underlying differential mRNA expression and transposon
      activity.

PMID- 23547921
TI  - The pain, agitation, and delirium practice guidelines for adult critically ill
      patients: a post-publication perspective.
AB  - The recently published Clinical Practice Guidelines for the Management of Pain,
      Agitation, and Delirium in Adult Patients in the Intensive Care Unit differ from
      earlier guidelines in the following ways: literature searches were performed in
      eight databases by a professional librarian; psychometric validation of
      assessment scales was considered in their recommendation; discrepancies in
      recommendation votes by guideline panel members are available in online
      supplements; and all recommendations were made exclusively on the basis of
      evidence available until December of 2010. Pain recognition and management
      remains challenging in the critically ill. Patient outcomes improve with routine
      pain assessment, use of co-analgesics and administration as well as dose
      adjustment of opiates to patient needs. Thoracic epidurals help ease patients
      undergoing abdominal aortic surgery. Little data exists to guide clinicians as to
      the type or dose of co-analgesics; no opiate choice is associated with better
      patient outcomes. Lighter or no sedation is beneficial, and interruption is
      desirable in patients who require deep sedation for specific pathologic states.
      Delirium screening is probably useful; no treatment modality can be unequivocally
      recommended, and the benefit of prophylaxis is established only for early
      mobilization. The details of these recommendations, as well as more recent
      publications that complement the guidelines, are provided in this commentary.

PMID- 23547922
TI  - Pathophysiology and treatment of focal segmental glomerulosclerosis: the role of
      animal models.
AB  - Focal segmental glomerulosclerosis (FSGS) is a kidney disease with progressive
      glomerular scarring and a clinical presentation of nephrotic syndrome. FSGS is a
      common primary glomerular disorder that causes renal dysfunction which progresses
      slowly over time to end-stage renal disease. Most cases of FSGS are idiopathic
      Although kidney transplantation is a potentially curative treatment, 40% of
      patients have recurrence of FSGS after transplantation. In this review a brief
      summary of the pathogenesis causing FSGS in humans is given, and a variety of
      animal models used to study FSGS is discussed. These animal models include the
      reduction of renal mass by resecting 5/6 of the kidney, reduction of renal mass
      due to systemic diseases such as hypertension, hyperlipidemia or SLE, drug
      induced FSGS using adriamycin, puromycin or streptozotocin, virus-induced FSGS,
      genetically-induced FSGS such as via Mpv-17 inactivation and alpha-actinin 4 and
      podocin knockouts, and a model for circulating permeability factors. In addition,
      an animal model that spontaneously develops FSGS is discussed. To date, there is
      no exact understanding of the pathogenesis of idiopathic FSGS, and there is no
      definite curative treatment. One requirement facilitating FSGS research is an
      animal model that resembles human FSGS. Most animal models induce secondary forms
      of FSGS in an acute manner. The ideal animal model for primary FSGS, however,
      should mimic the human primary form in that it develops spontaneously and has a
      slow chronic progression. Such models are currently not available. We conclude
      that there is a need for a better animal model to investigate the pathogenesis
      and potential treatment options of FSGS.

PMID- 23547920
TI  - Neuroinflammation and psychiatric illness.
AB  - Multiple lines of evidence support the pathogenic role of neuroinflammation in
      psychiatric illness. While systemic autoimmune diseases are well-documented
      causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with
      psychotic symptoms often go under-recognized. Parallel to the link between
      psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological
      abnormalities occur in classical psychiatric disorders (for example, major
      depressive, bipolar, schizophrenia, and obsessive-compulsive disorders).
      Investigations into the pathophysiology of these conditions traditionally
      stressed dysregulation of the glutamatergic and monoaminergic systems, but the
      mechanisms causing these neurotransmitter abnormalities remained elusive. We
      review the link between autoimmunity and neuropsychiatric disorders, and the
      human and experimental evidence supporting the pathogenic role of
      neuroinflammation in selected classical psychiatric disorders. Understanding how
      psychosocial, genetic, immunological and neurotransmitter systems interact can
      reveal pathogenic clues and help target new preventive and symptomatic therapies.

PMID- 23547923
TI  - Camel whey protein enhances diabetic wound healing in a streptozotocin-induced
      diabetic mouse model: the critical role of beta-Defensin-1, -2 and -3.
AB  - BACKGROUND: Delayed wound healing is considered one of the most serious diabetes
      associated complications. The presence of replicating organisms such as bacteria
      within a diabetic's wound is considered one of the most important factors that
      impair cutaneous wound healing and the potential cellular and/or molecular
      mechanisms that are involved in the healing process. Defensins, which are anti
      microbial peptides, have potent bactericidal activity against a wide spectrum of
      the bacterial and fungal organisms that are commonly responsible for wound
      infections. We recently demonstrated that camel whey proteins (WPs) expedite the
      healing of diabetic wounds by enhancing the immune response of wounded tissue
      cells and by alleviating some of the diabetic complications. METHODS: In the
      present study, we investigated the effects of WP supplementation on the mRNA and
      protein expression levels of beta-defensin-1 (BD-1), 2 and 3 and subsequently on
      the wound healing process in a streptozotocin (STZ)-induced diabetic mouse model.
      In this study, three groups of mice were used (10 mice per group): group 1, the
      non-diabetic mice (control); group 2, the diabetic mice; and group 3, the
      diabetic mice that received a daily supplement of undenatured WP (100 mg/kg of
      body weight) via oral gavage for 1 month. RESULTS: Compared with the non-diabetic
      control mice, the diabetic mice exhibited delayed wound closure that was
      characterized by a reduction in hydroxyproline content (indicator of collagen
      deposition), a marked elevation in free radical levels and a prolonged elevation
      in the levels of inflammatory cytokines, including interleukin-6 (IL-6),
      transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF
      alpha). Interestingly, compared with the diabetic mice that did not receive WP
      supplementation, the diabetic mice with WP had an accelerated closure and healing
      process of their wounds. The WP supplementation also decreased their levels of
      free radicals and restored their hydroxyproline content; proinflammatory cytokine
      levels; and expression of BD-1, 2 and 3 in the wounded tissue. CONCLUSION: WP
      supplementation may be beneficial for improving the healing and closure of
      diabetic wounds.

PMID- 23547925
TI  - alpha-Palladation of imines as entry to dehydrogenative Heck reaction: aerobic
      oxidative cyclization of N-allylimines to pyrroles.
AB  - We report here a palladium(II)-catalyzed oxidative cyclization reaction of N
      allylimines derived from methyl ketones, typically acetophenones, affording
      pyrrole derivatives at room temperature under oxygen atmosphere. The reaction
      likely proceeds through alpha-palladation of the imine followed by olefin
      migratory insertion and beta-hydride elimination, thus representing a new example
      of aerobic dehydrogenative Heck cyclization.

PMID- 23547924
TI  - The aggregate effects of multiple comorbid risk factors on cognition among HIV
      infected individuals.
AB  - This study developed and then cross-validated a novel weighting algorithm based
      on multiple comorbid risk factors (stimulant use, vascular disease, hepatitis C,
      HIV disease severity, cognitive reserve) to predict cognitive functioning among
      366 HIV+ adults. The resultant "risk severity score" was used to differentially
      weight, as a function of age, the impact and magnitude of multiple risk factors
      on cognition. Among older adults (>=50 years) the risk severity index was
      differentially predictive of learning/memory and verbal fluency, whereas among
      younger adults it was linked to working memory and executive function. Cognitive
      reserve was found to be the most robust predictor of neurocognition.

PMID- 23547926
TI  - Membrane mimetics induce helix formation and oligomerization of the chloride
      intracellular channel protein 1 transmembrane domain.
AB  - Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can
      exist either as a soluble monomer or in an integral membrane form. The
      transmembrane domain (TMD), implicated in membrane penetration and pore
      formation, comprises helix alpha1 and strand beta2 of the N-domain of soluble
      CLIC1. The mechanism by which the TMD binds, inserts, and oligomerizes in
      membranes to form a functional chloride channel is unknown. Here we report the
      secondary, tertiary, and quaternary structural changes of the CLIC1 TMD as it
      partitions between an aqueous and membrane-mimicking environment. A synthetic 30
      mer peptide comprising the TMD was examined in 2,2,2-trifluoroethanol, sodium
      dodecyl sulfate (SDS) micelles, and 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) liposomes using far-ultraviolet circular dichroism and
      fluorescence spectroscopy. Data obtained in the presence of SDS micelles and POPC
      liposomes show that Trp35 and Cys24 have reduced solvent accessibility,
      indicating that the peptide adopts an inserted orientation. The peptide assumes a
      helical structure in the presence of these mimetics, consistent with its
      predicted membrane conformation. This acquisition of secondary structure is
      concentration-dependent, suggesting an oligomerization event. Stable dimeric and
      trimeric species were subsequently identified using SDS-polyacrylamide gel
      electrophoresis. We propose that, in the vicinity of membranes, the mixed
      alpha/beta TMD in CLIC1 rearranges to form a helix that then likely dimerizes via
      noncovalent helix-helix interactions to form a membrane-competent protopore
      complex. Such oligomerization would be essential for forming a functional ion
      channel, given that each CLIC1 monomer possesses only a single TMD. This work
      highlights the central role of the TMD in CLIC1 function: It is capable of
      promoting membrane insertion and dimerization in the absence of the C-domain and
      large portions of the N-domain.

PMID- 23547927
TI  - One-pot high-throughput synthesis of a 160-membered library of methyl 3,5-diaryl
      isoxazoline-5-carboxylate pharmacophores by a 2.2.2-component reaction.
AB  - A simple and efficient methodology has been developed for the synthesis of methyl
      3,5-diaryl-isoxazoline-5-carboxylates in a high-throughput fashion. This was
      accomplished in one-pot by a sequence of three 2-component reactions steps (2.2.2
      CR), whereby compounds were obtained in overall 30-66% isolated yields. The
      functional group diversity was established by synthesizing a 160-membered
      library. 

PMID- 23547928
TI  - Strong hyperconjugative interactions in isolated and water complexes of
      desflurane: a theoretical investigation.
AB  - Ab initio MP2/aug-cc-pvDZ and density functional B3LYP calculations with the 6
      311++G(d,p) basis set are performed to investigate the conformation of desflurane
      (CHF2OCHFCF3), its acidity/basicity and its interaction with one water molecule.
      The calculations include the optimized geometries, the harmonic frequencies of
      relevant vibrational modes, the binding energies with water, and a detailed
      natural bond orbital (NBO) analysis Iincluding the NBO charges, the hybridization
      of the C atoms and the intra- and intermolecular hyperconjugations. The relative
      energies of the two most stable conformers are discussed as a function of the
      total hyperconjugative energies resulting from the interaction of lone pairs of
      the O and F atoms to the different antibonding orbitals of desflurane. The proton
      affinity is the same for both conformers but the acidity of the CH bond is larger
      for the less stable conformer. The binding energies of the complexes of two
      desflurane conformers with one water molecule range from -2.75 to -3.23 kcal mol(
      1). Depending on the structure of the complexes, the CH bonds involved in the
      interaction are contracted or elongated. The sigma*(CH) occupation predominates
      over the hybridization effect in determining the CH bond length. There is an
      unexpected charge transfer to the external OH bond of the water molecule. This
      effect is in good agreement with theoretical data on the complexes between
      fluorinated dimethyl ethers and water and seems to depend on the number of F
      atoms implanted on the ether molecule. 

PMID- 23547929
TI  - Novel activators and inhibitors of epithelial sodium channels (ENaCs): state of
      the art.

PMID- 23547930
TI  - ENaC inhibitors and airway re-hydration in cystic fibrosis: state of the art.
AB  - Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene
      encoding the chloride channel "cystic fibrosis transmembrane conductance
      regulator" (CFTR). The lack of functional CFTR in CF airways leads to impaired
      ion and fluid homeostasis of the fluid layer which lines the airway surfaces
      (ASL). The ASL is important for proper ciliary beat and clearance of mucus from
      the airways. According to the "low volume hypothesis", CF airway epithelia
      hyperabsorb sodium via the epithelial sodium channel (ENaC). Although the
      contribution of ENaC to CF pathogenesis is still under debate, there is
      convincing data demonstrating that re-hydration of the ASL might improve
      mucociliary clearance in CF patients. ASL re-hydration might, amongst other
      things, be achieved by a block of airway transepithelial sodium absorption with
      inhibitors of ENaC. This mini-review article describes the role of ENaC in ASL
      fluid homeostasis and rehydration, and summarizes the current state of the art in
      the discovery and establishment of compounds which inhibit ENaC activity and may
      represent pharmacological tools for the treatment of CF.

PMID- 23547931
TI  - Treatment of pulmonary edema by ENaC activators/stimulators.
AB  - Lungs contain a particular amount of fluid that is crucial for proper lung
      function. This fluid content is tightly controlled within certain limits. Fluid
      accumulation in the alveolar airspace impairs gas exchange and represents a
      lifethreatening condition referred to as pulmonary edema. Ion transport processes
      by pulmonary epithelia represent a mechanism, responsible for fluid absorption
      from the airspace. Thus, it is obvious to consider ion transport processes as
      target for therapeutic interventions in pulmonary edema. The principle mechanism
      responsible for fluid absorption from the airspace is: Na(+) diffuses through
      luminal Na(+) channels into epithelial cells and is extruded by Na(+)/K(+)
      ATPases at the basolateral side. This process generates an osmotic gradient that
      represents the driving force for fluid absorption. The rate of Na(+) absorption
      is limited by the number/activity of Na+ channels in the luminal membrane of
      alveolar epithelial cells. Although different Na+ channels have been identified,
      the epithelial Na+ channel (ENaC) is a major player that participates in Na(+)
      driven fluid absorption and thus a suitable target for the treatment of pulmonary
      edema. This article reviews cellular mechanisms by which ENaC activity can be
      increased in alveolar epithelia (lectins, proteases, beta-adrenoceptors, mineralo
      /glucocorticoid-receptors). These mechanisms are involved in regulating ENaC
      dependent fluid absorption under physiological conditions. Additionally, pre
      clinical as well as some preliminary clinical studies revealed that "ENaC
      activators/stimulators" (beta2-adrenoceptor agonists and mineralo-/glucocorticoid
      receptor agonists) could be beneficial for therapeutic interventions in patients
      with pulmonary edema. However, the outcome of subsequently performed multicenter
      clinical trials with "ENaC-activators/stimulators" for treatment of patients with
      pulmonary edema was disappointing.

PMID- 23547933
TI  - ENaC modulators and renal disease.
AB  - The epithelial sodium channel (ENaC) plays an essential role in transepithelial
      sodium reabsorption in the renal connecting tubule and collecting duct.
      Therefore, controlling ENaC activity is an important regulatory event in
      electrolyte and extracellular volume homeostasis, and thus in the control of
      blood pressure. Many independent signaling pathways converge on ENaC, although
      the most important for its physiological role is the enhancement of channel
      activity by the steroid hormone aldosterone. In this review, we briefly summarize
      current knowledge about ENaC regulation and the different chemical compounds
      available to directly or indirectly modify channel function. In addition, current
      and possible clinical uses of ENaC and aldosterone antagonists are highlighted.

PMID- 23547932
TI  - ENaC regulation by proteases and shear stress.
AB  - Epithelial Na(+) channels (ENaCs) are comprised of subunits that have large
      extracellular regions linked to membrane spanning domains where the channel pore
      and gate reside. A variety of external factors modify channel activity by
      interacting at sites within extracellular regions that lead to conformational
      changes that are transmitted to the channel gate and alter channel open
      probability. Our review addresses two external factors that have important roles
      in regulating channel activity, proteases and laminar shear stress.

PMID- 23547934
TI  - ENaC in the brain--future perspectives and pharmacological implications.
AB  - The epithelial sodium channel/degenerin (ENaC/deg) family of ion channels is
      formed by a large number of genes with variable tissue expression patterns and
      physiological roles. ENaC is a non-voltage gated, constitutively active channel
      highly selective for sodium. ENaC is formed by three homologous subunits, alpha,
      beta and gamma, and a fourth subunit (delta) has been found in human and monkeys
      that can substitute alpha to form functional channels. The best-characterized
      role of ENaC is to serve as a rate-limiting step in transepithelial sodium
      reabsorption in the distal part of the kidney tubule and other tight epithelia.
      However, ENaC subunits are also found in the peripheral and central nervous
      system, where their functional roles are only beginning to be understood. In this
      review, we mainly focus on the putative pathophysiological roles of ENaC channels
      in the central nervous system and their potential value as drug targets in
      neurodegenerative disorders and the central control of blood pressure.

PMID- 23547935
TI  - Kinases as targets for ENaC regulation.
AB  - Amiloride-sensitive epithelial sodium channels (ENaCs) transport Na+ and are
      essential for salt and fluid homeostasis across epithelial tissues. Several
      pathological conditions of renal and pulmonary tissues are associated with
      abnormal ENaC function. The signalling pathways that regulate ENaC activity
      utilise a number of kinases. Over recent years, more have been identified and
      their mechanisms of action expanded. The functions of SGK and PKA are the best
      understood and both up-regulate ENaC activity. SGK is an important target of PI3K
      via PDK1 and TORC2 whilst PKA is linked with the activity of other kinases that
      have complementary effects. CK2, GRK2, IKKbeta and PKD1 also up-regulate ENaC. In
      contrast, PKC, ERK1/2 and AMPK are inhibitory. Two key convergence targets for
      kinase action persist. These are phosphorylation of Nedd4-2 and the beta and
      gamma subunits of ENaC. Depending on the sites targeted, phosphorylation
      predominantly promotes or decreases association between these proteins to
      regulate ENaC retrieval and its subsequent abundance in the membrane. Alternative
      emerging targets include proteins involved in the translocation and recycling of
      ENaC channels to the membrane. Targeting kinases to modify ENaC function in vivo
      has shown some promise. Inactivation of SGK has produced mild but positive
      effects on renal function. Activating PKA has shown potential in lung
      pathologies. Inhibition of PI3K and PKB may prove useful in diabetic related
      alterations in renal Na+ handling, as could activation of AMPK, which may also
      have potential in the treatment of pulmonary pathologies associated with elevated
      ENaC activity.

PMID- 23547936
TI  - Profile control of inkjet printed silver electrodes and their application to
      organic transistors.
AB  - We report on the cross-sectional profile control of printed electrodes fabricated
      from silver nanoparticle inks with water-based solvents by inkjet printing.
      Systematically varying the ambient conditions and time for the drying process
      corresponded to changes in electrode shape. In general, lower humidity levels
      resulted in concave electrode profiles due to the coffee-ring effect, while
      higher humidity levels resulted in convex profiles. Printed capacitors with
      trapezoidal-shaped lower electrodes showed much better electrical breakdown
      strength than those with concave-shaped lower electrodes. Solution-processed
      organic thin-film transistors with trapezoidal gate electrodes operated
      reproducibly and exhibited good electrical characteristics with very low gate
      leakage currents. The methods can be utilized in the fabrication of printed
      electronic devices with stacked layers, such as thin-film capacitors and
      transistors.

PMID- 23547937
TI  - Myocardial protection against global ischemia with Krebs-Henseleit buffer-based
      cardioplegic solution.
AB  - BACKGROUND: The Krebs-Henseleit buffer is the best perfusion solution for
      isolated mammalian hearts. We hypothesized that a Krebs-Henseleit buffer-based
      cardioplegic solution might provide better myocardial protection than well-known
      crystalloid cardioplegic solutions because of its optimal electrolyte and glucose
      levels, presence of buffer systems, and mild hyperosmolarity. METHODS: Isolated
      Langendorff-perfused rat hearts were subjected to either global ischemia without
      cardioplegia (controls) or cardioplegic arrest for either 60 or 180 min, followed
      by 120 min of reperfusion. The modified Krebs-Henseleit buffer-based cardioplegic
      solution (mKHB) and St. Thomas' Hospital solution No. 2 (STH2) were studied.
      During global ischemia, the temperatures of the heart and the cardioplegic
      solutions were maintained at either 37 degrees C (60 min of ischemia) or 22
      degrees C (moderate hypothermia, 180 min of ischemia). Hemodynamic parameters
      were registered throughout the experiments. The infarct size was determined
      through histochemical examination. RESULTS: Cardioplegia with the mKHB solution
      at moderate hypothermia resulted in a minimal infarct size (5 +/- 3%) compared to
      that in the controls and STH2 solution (35 +/- 7% and 19 +/- 9%, respectively; P
      < 0.001, for both groups vs. the mKHB group). In contrast to the control and STH2
      treated hearts, no ischemic contracture was registered in the mKHB group during
      the 180-min global ischemia. At normothermia, the infarct sizes were 4 +/- 3%, 72
      +/- 6%, and 70 +/- 12% in the mKHB, controls, and STH2 groups, respectively (P <
      0.0001). In addition, cardioplegia with mKHB at normothermia prevented ischemic
      contracture and improved the postischemic functional recovery of the left
      ventricle (P < 0.001, vs. STH2). CONCLUSIONS: The data suggest that the Krebs
      Henseleit buffer-based cardioplegic might be superior to the standard crystalloid
      solution (STH2).

PMID- 23547938
TI  - A mass-tagging approach for enhanced sensitivity of dynamic cytokine detection
      using a label-free biosensor.
AB  - Monitoring cytokine release by cells allows the investigation of cellular
      response to specific external stimuli, such as pathogens or candidate drugs.
      Unlike conventional colorimetric techniques, label-free detection of cytokines
      enables studying cellular secretions in real time by eliminating additional wash
      and labeling steps after the binding step. However, label-free techniques that
      are based on measuring mass accumulation on a sensor surface are challenging for
      measuring small cytokines binding to much larger capture agents (usually
      antibodies) because the relative signal change is small. This problem is
      exacerbated when the capturing antibodies desorb from the surface, a phenomenon
      that almost inevitably occurs in immunoassays but is rarely accounted for. Here,
      we demonstrate a quantitative dynamic detection of interleukine-6 (IL-6), a pro
      inflammatory cytokine, using an interferometric reflectance imaging sensor
      (IRIS). We improved the accuracy of the quantitative analysis of this relatively
      small protein (21 kDa) by characterizing the antibody desorption rate and
      compensating for the antibody loss during the binding experiment. By correcting
      for protein desorption, we achieved an analytical limit of detection at 19 ng/mL
      IL-6 concentration. We enhanced the sensitivity by 7-fold by using detection
      antibodies that recognize a different epitope of the cytokine. We demonstrate
      that these detection antibodies, which we call "mass tags", can be used
      concurrently with the target analyte to eliminate an additional wash and binding
      step. Finally, we report successful label-free detection of IL-6 in cell culture
      medium (with 10% serum) with comparable signal to that obtained in PBS. This work
      is the first to report quantitative dynamic label-free detection of small protein
      in a complex biological fluid using IRIS.

PMID- 23547939
TI  - Is tubeless percutaneous nephrolithotomy really less injurious than standard in
      the midterm?
AB  - PURPOSE: To compare renal injury and vascular resistance between standard and
      tubeless percutaneous nephrolithotomy (PCNL) in patients who had undergone
      procedures for kidney stone by using colored Doppler ultrasonography (CDUS).
      PATIENTS AND METHODS: All consecutive PCNLs were evaluated between 2009 and 2011.
      Patients in whom access was in the lower pole, and who regularly visited our
      outpatient clinic were enrolled in the study. Patients who underwent standard
      PCNL were included in group 1, and patients who underwent tubeless PCNL were
      included in group 2. All data were collected from patients' files. CDUS was
      performed to evaluate the resistive index (RI), parenchymal thickness, and
      parenchymal echogenicity before the operation, in the early postoperative period
      (7 days after catheter removal in group 1 and 7 days postoperatively in group 2),
      and during the midterm period (6 months postoperatively). Statistical
      significance was accepted at P<0.05. RESULTS: The mean patient age was 47.54+/
      13.26 years. There were 33 patients in group 1 and 28 patients in group 2. The
      mean follow-up duration was 10.71+/-1.2 months. There were no significant
      differences in demographic data between the two groups. The hospital stay was
      longer in group 1 than in group 2 (P=0.038). The mean operative time was shorter
      in group 2 than in group 1 (P=0.001). An increase in RI and a decrease in
      parenchymal thickness in the midterm follow-up period were noted when compared
      with the preoperative RI kidneys that had undergone operations in the lower pole.
      CONCLUSIONS: Although tubeless PCNL was successful and was associated with a
      shorter hospital stay and less kidney damage in the short-term period compared
      with standard PCNL, both procedures may cause an almost equal degree of damage in
      the midterm.

PMID- 23547940
TI  - Mortality among British Columbians testing for hepatitis C antibody.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a major preventable and
      treatable cause of morbidity and mortality. The ability to link population based
      centralized laboratory HCV testing data with administrative databases provided a
      unique opportunity to compare mortality between HCV seronegative and seropositive
      individuals. Through the use of laboratory testing patterns and results, the
      objective of this study was to differentiate the viral effects of mortality due
      to HCV infection from risk behaviours/activities that are associated with
      acquisition of HCV infection. METHODS: Serological testing data from the British
      Columbia (BC) Centre for Disease Control Public Health Microbiology and Reference
      Laboratory from 1992-2004 were linked to the BC Vital Statistics Agency death
      registry. Four groups of HCV testers were defined by their HCV antibody (anti
      HCV) testing patterns: single non-reactive (SNR); serial multiple tested non
      reactive (MNR); reactive at initial testing (REAC); and seroconverter (SERO)
      (previously seronegative followed by reactive, a marker for incident infection).
      Standardized mortality ratios (SMRs) were calculated to compare the relative risk
      of all cause and disease specific mortality to that of the BC population for each
      serological group. Time dependent Cox proportional hazard regression was used to
      compare hazard ratios (HRs) among HCV serological groups. RESULTS: All anti-HCV
      testers had higher SMRs than the BC population. Referent to the SNR group, the
      REAC group had higher risks for liver (HR: 9.62; 95% CI=8.55-10.87) and drug
      related mortality (HR: 13.70; 95% CI=11.76-16.13). Compared to the REAC group,
      the SERO group had a lower risk for liver (HR: 0.53; 95% CI=0.24-0.99), but a
      higher risk for drug related mortality (HR: 1.54; 95% CI=1.12-2.05). CONCLUSIONS:
      These findings confirm that individuals who test anti-HCV positive have increased
      mortality related to progressive liver disease, and that a substantial proportion
      of the mortality is attributable to drug use and risk behaviours/activities
      associated with HCV acquisition. Mortality reduction in HCV infected individuals
      will require comprehensive prevention programming to reduce the harms due to
      behaviours/activities which relate to HCV acquisition, as well as HCV treatment
      to prevent progression of chronic liver disease.

PMID- 23547941
TI  - Clinical governance network for clinical audit to improve quality in epithelial
      ovarian cancer management.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynecological
      cancer. Several hospitals throughout the region provide primary treatment for
      these patients and it is well know that treatment quality is correlated to the
      hospital that delivers. The aim of this study was to investigate the management
      and treatment of EOC in a Region of the North Italy (Emilia-Romagna, Italy).
      METHODS: A multidisciplinary group made up of 11 physicians and 3
      biostatisticians was formed in 2009 to perform clinical audits in order to
      identify quality indicators and to develop Region-wide workup in accordance with
      the principles of evidence-based medicine (EBM). The rationale was that, by
      setting up an oncogynecology network so as to achieve the best clinical practice,
      critical points would decrease or even be eliminated. Analysis of cases was based
      on the review of the medical records. RESULTS: 614 EOC patients treated between
      2007 and 2008 were identified. We found only 2 high-volume hospitals (>= 21
      patients/year), 3 medium-volume hospitals (11-20 operated patients/year), and 7
      low-volume hospitals (<= 10 operated patients /year). Only 222 patients (76.3%)
      had a histological diagnosis, FIGO surgical staging was reported only in 206
      patients (70.9%) but not all standard surgical procedures were always performed,
      residual disease were not reported in all patients. No standard number of
      neoadjuvant chemotherapy cycles was observed. CONCLUSIONS: The differences in
      terms of treatments provided led the multidisciplinary group to identify
      reference centers, to promote centralization, to ensure uniform and adequate
      treatment to patients treated in regional centers and to promote a new audit
      involving all regional hospitals to a complete review of the all the EOC
      patients.

PMID- 23547942
TI  - Detection of key factors affecting lycopene in vitro accessibility.
AB  - On the basis of a Plackett-Burman experimental design for a resolution IV level
      obtained via a foldover strategy, the effect of 11 factors on lycopene in vitro
      accessibility was investigated. The selected factors were thermal treatment (X1),
      olive oil addition (X2), gastric pH (X3), gastric digestion time (X4), pepsin
      concentration (X5), intestinal pH (X6), pancreatin concentration (X7), bile salts
      concentration (X8), colipase addition (X9), intestinal digestion time (X10), and
      intestinal digestion speed (X11). Tomato passata was used as a natural source of
      lycopene. Samples were collected after gastric and intestinal digestion, and from
      the micellar phase, to quantify the (all-E)-lycopene and its (Z)-isomers by HPLC.
      Except for X3, X6, X7, and X11, the other factors studied explained lycopene in
      vitro accessibility, mainly regarding intestinal digestion, with R(2) values >=
      0.60. Our results showed that the accessibility of lycopene is influenced by the
      conditions applied during in vitro intestinal digestion. 

PMID- 23547943
TI  - TRACER: a resource to study the regulatory architecture of the mouse genome.
AB  - BACKGROUND: Mammalian genes are regulated through the action of multiple
      regulatory elements, often distributed across large regions. The mechanisms that
      control the integration of these diverse inputs into specific gene expression
      patterns are still poorly understood. New approaches enabling the dissection of
      these mechanisms in vivo are needed. RESULTS: Here, we describe TRACER
      (http://tracerdatabase.embl.de), a resource that centralizes information from a
      large on-going functional exploration of the mouse genome with different
      transposon-associated regulatory sensors. Hundreds of insertions have been mapped
      to specific genomic positions, and their corresponding regulatory potential has
      been documented by analysis of the expression of the reporter sensor gene in
      mouse embryos. The data can be easily accessed and provides information on the
      regulatory activities present in a large number of genomic regions, notably in
      gene-poor intervals that have been associated with human diseases. CONCLUSIONS:
      TRACER data enables comparisons with the expression pattern of neighbouring
      genes, activity of surrounding regulatory elements or with other genomic
      features, revealing the underlying regulatory architecture of these loci. TRACER
      mouse lines can also be requested for in vivo transposition and chromosomal
      engineering, to analyse further regions of interest.

PMID- 23547944
TI  - Homology modeling and virtual screening approaches to identify potent inhibitors
      of VEB-1 beta-lactamase.
AB  - BACKGROUND: blaVEB-1 is an integron-located extended-spectrum beta-lactamase gene
      initially detected in Escherichia coli and Pseudomonas aeruginosa strains from
      south-east Asia. Several recent studies have reported that VEB-1-positive strains
      are highly resistant to ceftazidime, cefotaxime and aztreonam antibiotics. One
      strategy to overcome resistance involves administering antibiotics together with
      beta-lactamase inhibitors during the treatment of infectious diseases. During
      this study, four VEB-1 beta-lactamase inhibitors were identified using computer
      aided drug design. METHODS: The SWISS-MODEL tool was utilized to generate three
      dimensional structures of VEB-1 beta-lactamase, and the 3D model VEB-1 was
      verified using PROCHECK, ERRAT and VERIFY 3D programs. Virtual screening was
      performed by docking inhibitors obtained from the ZINC Database to the active
      site of the VEB-1 protein using AutoDock Vina software. RESULTS AND CONCLUSION:
      Homology modeling studies were performed to obtain a three-dimensional structure
      of VEB-1 beta-lactamase. The generated model was validated, and virtual screening
      of a large chemical ligand library with docking simulations was performed using
      AutoDock software with the ZINC database. On the basis of the dock-score, four
      molecules were subjected to ADME/TOX analysis, with ZINC4085364 emerging as the
      most potent inhibitor of the VEB-1 beta-lactamase.

PMID- 23547945
TI  - Change in product selectivity during the production of glyceric acid from
      glycerol by Gluconobacter strains in the presence of methanol.
AB  - To enhance the value-added use of methanol-containing raw glycerol derived from
      biodiesel fuel production, the effect of methanol supplementation on glyceric
      acid (GA) production by Gluconobacter spp. was investigated. We first conducted
      fed-batch fermentation with Gluconobacter frateurii NBRC103465 using raw glycerol
      as a feeding solution. GA productivity decreased with increasing dihydroxyacetone
      (DHA) formation when the raw glycerol contained methanol. The results of this
      experiment and comparative experiments using a synthetic solution modeled after
      the raw glycerol indicate that the presence of methanol caused a change in the
      concentrations of GA and DHA, two glycerol derivatives produced during
      fermentation. Other Gluconobacter spp. also decreased GA production in the
      presence of 1% (v/v) methanol. In addition, purified membrane-bound alcohol
      dehydrogenase (mADH) from Gluconobacter oxydans, which is a key enzyme in GA
      production, showed a decrease in dehydrogenase activity toward glycerol as the
      methanol concentration increased. These results strongly suggest that the
      observed decrease in GA production by Gluconobacter spp. resulted from the
      methanol-induced inhibition of mADH-mediated glycerol oxidation.

PMID- 23547946
TI  - The prevalence of insomnia and its socio-demographic and clinical correlates in
      older adults in rural China: a pilot study.
AB  - OBJECTIVES: To investigate the prevalence of insomnia (DIS: difficulty initiating
      sleep; DMS: difficulty maintaining sleep; and EMA: early morning awakening), its
      socio-demographic and clinical correlates, and the treatment patterns in older
      adults in rural China. METHOD: A sample of 263 subjects was recruited in Mianyang
      and interviewed using standardized instruments. Basic socio-demographic and
      clinical data were collected. RESULTS: The expected mean total sleep time (TST)
      of the whole sample was 6.8 +/- 2.2 hours, and the actual mean TST was 6.3 +/-
      2.1 hours. The 1-year prevalence of at least one type of insomnia was 7.6%; the
      rates of DIS, DMS, and EMA were 5.7%, 7.2%, and 6.8%, respectively. On
      multivariate analyses, female sex and psychiatric disorders were independently
      associated with more frequent insomnia. CONCLUSION: Insomnia is not uncommon in
      older adults in rural China, and the low percentage of subjects treated suggests
      that improved access to treatment might be indicated.

PMID- 23547947
TI  - Spirocyclic dihydropyridines by electrophile-induced dearomatizing cyclization of
      N-alkenyl pyridinecarboxamides.
AB  - On treatment with acylating or sulfonylating agents, N-alkenyl pyridine
      carboxamides (N-pyridinecarbonyl enamines) undergo a dearomatizing cyclization
      initiated by pyridine acylation and followed by intramolecular trapping of the
      resulting pyridinium cation. The products are spirocyclic dihydropyridines which
      may be further elaborated to spirocyclic heterocycles with drug-like features.

PMID- 23547948
TI  - Novel approaches for the synthesis of a library of fluorescent chromenopyrimidine
      derivatives.
AB  - A library of some new fluorescent chromenopyrimidine derivatives has been
      synthesized by new approaches. Water-promoted and one-pot reaction can produce
      new dialkylylamino)-5H-chromeno[2,3-d]pyrimidin-2-yl) phenols. These compounds
      can also be produced using domino reaction. Two parallel methods are compared.
      Novel N-alkyl-N-phenyl-5H-chromeno[2,3-d]-pyrimidin-4-amines and 4-alkoxy-5H
      chromeno[2, 3-d]pyrimidines are synthesized by Lewis-acid catalyzed reactions.
      The fluorescence emission intensity of the four compounds from each of libraries
      after excitation in 290 nm is measured. Compound 2-(4,5-bis(N-methyl-N
      phenylamino)-5H-chromeno[2,3-d]pyrimidin-2-yl)phenol was isolated as a byproduct.
      The details of an interesting exchangeable intramolecular H- bonding of two of
      the new compounds are reported by X-ray analysis data. 

PMID- 23547950
TI  - Luminescent electrophoretic particles via miniemulsion polymerization for night
      vision electrophoretic displays.
AB  - A novel glowing electrophoretic display (EPD) is achieved by luminescent
      electrophoretic particles (EPs), which is potentially to improve the situation in
      which the existing EPDs disable in darkness. To combine both modes of reflective
      and emissive displays, a trilayer luminescence EP is designed and synthesized via
      an improved miniemulsion polymerization. The luminescence EP is composed of a
      pigment core, a polystyrene interlayer, and a fluorescent coating. The particle
      sizes are from 140 to 170 nm, and the size distribution is narrow. Their zeta
      potential value is -12.4 mV, which is enough to migrate in the electrophoretic
      fluid by the driving of an electric field. The display performance of the
      particles in an EPD cell has been characterized under the bias of 20 V. Both the
      reflectance (491 nm) and fluorescence (521 nm) intensities of the EPD cell
      remained in a constant range after 30 switches.

PMID- 23547951
TI  - Model reductions for inference: generality of pairwise, binary, and planar factor
      graphs.
AB  - We offer a solution to the problem of efficiently translating algorithms between
      different types of discrete statistical model. We investigate the expressive
      power of three classes of model-those with binary variables, with pairwise
      factors, and with planar topology-as well as their four intersections. We
      formalize a notion of "simple reduction" for the problem of inferring marginal
      probabilities and consider whether it is possible to "simply reduce" marginal
      inference from general discrete factor graphs to factor graphs in each of these
      seven subclasses. We characterize the reducibility of each class, showing in
      particular that the class of binary pairwise factor graphs is able to simply
      reduce only positive models. We also exhibit a continuous "spectral reduction"
      based on polynomial interpolation, which overcomes this limitation. Experiments
      assess the performance of standard approximate inference algorithms on the
      outputs of our reductions.

PMID- 23547949
TI  - Peak systolic velocity using color-coded tissue Doppler imaging, a strong and
      independent predictor of outcome in acute coronary syndrome patients.
AB  - BACKGROUND: Traditional echocardiographic methods like left ventricular ejection
      fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking
      (ST) based 2D strain carry important prognostic information in acute coronary
      syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its
      high time resolution, may further increase the prognostic value. Peak systolic
      velocity (PSV) of the basal segments of the left ventricle from TDI is a robust
      and user independent parameter. The aim was to investigate the prognostic value
      of PSV compared to EF, WMS, 2D strain and E/e'. METHODS: Echocardiographic images
      were collected and post processed in 227 ACS patients. Additional clinical data
      was prospectively gathered and patients were followed for 3-5 years regarding the
      combined endpoint of death or re-admission due to ACS or heart failure. RESULTS:
      The combined endpoint occurred in 85 (37%) patients. Those with an event had
      lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p<0.001). In a
      ROC analysis, the AUC was larger for PSV (0.75) than for EF (0.68), WMS (0.63),
      2D strain (0.67) and E/e'(0.70). The combined endpoint increased with decreasing
      PSV. When adjusting for differences in baseline characteristics in a COX
      regression model, PSV remained independently associated with outcome where the
      others did not. PSV was also less sensitive to image quality with fewer values
      missing or unacceptable for analysis. CONCLUSION: Peak systolic velocity (PSV) is
      a robust measurement that seems to have a strong and independent association with
      outcome compared to traditional echocardiographic measurements in ACS patients.

PMID- 23547952
TI  - Relative density-ratio estimation for robust distribution comparison.
AB  - Divergence estimators based on direct approximation of density ratios without
      going through separate approximation of numerator and denominator densities have
      been successfully applied to machine learning tasks that involve distribution
      comparison such as outlier detection, transfer learning, and two-sample
      homogeneity test. However, since density-ratio functions often possess high
      fluctuation, divergence estimation is a challenging task in practice. In this
      letter, we use relative divergences for distribution comparison, which involves
      approximation of relative density ratios. Since relative density ratios are
      always smoother than corresponding ordinary density ratios, our proposed method
      is favorable in terms of nonparametric convergence speed. Furthermore, we show
      that the proposed divergence estimator has asymptotic variance independent of the
      model complexity under a parametric setup, implying that the proposed estimator
      hardly overfits even with complex models. Through experiments, we demonstrate the
      usefulness of the proposed approach.

PMID- 23547954
TI  - Copper-catalyzed aerobic C(sp2)-H functionalization for C-N bond formation:
      synthesis of pyrazoles and indazoles.
AB  - A simple, practical, and highly efficient synthesis of pyrazoles and indazoles
      via copper-catalyzed direct aerobic oxidative C(sp(2))-H amination has been
      reported herein. This process tolerated a variety of functional groups under mild
      conditions. Further diversification of pyrazoles was also investigated, which
      provided its potential for drug discovery.

PMID- 23547953
TI  - Chronic kidney diseases in mixed ancestry south African populations: prevalence,
      determinants and concordance between kidney function estimators.
AB  - BACKGROUND: Population-based data on the burden of chronic kidney disease (CKD)
      in sub-Saharan Africa is still very limited. We assessed the prevalence and
      determinants of CKD, and evaluated the concordance of commonly advocated
      estimators of glomerular filtration rate (eGFR) in a mixed ancestry population
      from South Africa. METHODS: Participants were a population-based sample of adults
      selected from the Bellville-South community in the metropolitan city of Cape
      Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney
      Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and
      without adjustment for ethnicity). Kidney function staging used the Kidney
      Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions
      and kappa statistic were used to investigate determinants of CKD and assess the
      agreement between different estimators. RESULTS: The crude prevalence of CKD
      stage 3-5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD
      with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI
      equations with and without ethnicity correction. The highest agreement between
      GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity
      correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI:
      0.94-0.96). In multivariable logistic regression models, sex, age and known
      hypertension were consistently associated with CKD stage 3-5 across the 5
      estimators. CONCLUSIONS: The prevalence of CKD stages greater than 3 is the
      highest reported in Africa. This study provides evidence for support of the CKD
      EPI equation for eGFR reporting and CKD classification.

PMID- 23547955
TI  - Low-lying electronic states of Ir(n) clusters with n = 2-8 predicted at the DFT,
      CASSCF, and CCSD(T) levels.
AB  - Low-lying structures of the small iridum clusters Ir(n) (n = 2-8) were optimized
      using DFT methods. Ir2 and Ir3 were also optimized using the CASSCF method. MRCI
      SD (for Ir2) energies and CCSD(T) (for Ir2 and Ir3) energies of the leading
      configurations from the CASSCF calculations were done to predict the low-lying
      states. The normalized atomization energies (<AE>) for Ir(n) (n = 2-8) were
      calculated at the CCSD(T) level up to the complete basis set (CBS) limit in some
      cases using the B3LYP optimized geometries. The ground state for Ir2 is predicted
      to be (5)Deltag, and the ground state of Ir3 is linear (2)Deltag, with the
      D3h(4)A"1 state ~10 kcal/mol higher in energy at the CASSCF level without core
      valence corrections and ~15 kcal/mol higher at the CCSD(T)/CBS level with spin
      orbit and core-valence corrections. Inclusion of the spin orbit corrections in
      the normalized bond dissociation energies <AE> for Ir(n) is critical and will
      decrease the <AE> by ~15 kcal/mol for n >= 4. The <AE> for Ir(n) increases as n
      increases in general, and the <AE> is far from convergence to the bulk value at n
      = 8. The average coordination number (CN) and average bond length for the low
      energy Ir(n)clusters are far from being converged to the bulk values by n = 8.

PMID- 23547956
TI  - Energetics of protein stability at extreme environmental temperatures in
      bacterial trigger factors.
AB  - Trigger factor is the first molecular chaperone interacting cotranslationally
      with virtually all nascent polypeptides synthesized by the ribosome in bacteria.
      The stability of this primary folding assistant was investigated using trigger
      factors from the Antarctic psychrophile Pseudoalteromonas haloplanktis, the
      mesophile Escherichia coli, and the hyperthermophile Thermotoga maritima. This
      series covers nearly all temperatures encountered by living organisms. We show
      that proteins adapt their stability over the whole range of biological
      temperatures via adjustments of the same fundamental mechanisms, involving
      increases in enthalpic stabilization and decreases in unfolding rates, in
      parallel with the environmental temperature. Enthalpic stabilization in trigger
      factors is characterized by large increases in the melting temperature, T(m),
      ranging from 33 to 96.6  degrees C, associated with similarly large increases in
      unfolding enthalpy as revealed by differential scanning calorimetry. Stopped-flow
      spectroscopy shows that the folding rate constants for the three investigated
      proteins are similar, whereas the unfolding rate constants differ by several
      orders of magnitude, revealing that kinetic resistance to unfolding drives
      adjustments of protein stability. While the unusual stability of
      hyperthermophilic proteins has attracted much attention, this study indicates
      that they are an extreme case of a more general continuum, the other extreme
      being represented by natively unstable proteins from psychrophiles.

PMID- 23547957
TI  - Structural requirements for producing solvent-free room temperature liquid
      fullerenes.
AB  - A new class of solvent-free room temperature liquid fullerenes was synthesized by
      attaching a single substituent of 1,3,5-tris(alkyloxy)benzene unit to C60 or C70
      under the Prato conditions. Although the C60 monoadducts were single components
      after chromatographic purification, the C70 monoadducts were isomeric mixtures
      due to the prolate spheroidal pi-chromophore. The alkyl chain length of the
      substituents significantly affected both melting points and rheological behavior
      of the fullerene derivatives. When the alkyl chains were short, the
      intermolecular pi-pi interactions of adjacent fullerene cores led to a melting
      point higher than room temperature. In contrast, in the case of exceedingly long
      alkyl chains, such as eicosyl (-C20H41) and docosanyl (-C22H45) groups, the van
      der Waals interactions among neighboring alkyl chains became dominant.
      Accordingly, only medium alkyl chain lengths could provide solvent-free fluidic
      fullerenes with low melting points. The rheological measurements of the liquid
      fullerenes at 25  degrees C revealed their unique liquid characteristics;
      molecular-level friction (or viscosity) and nanometer-scale clustering were
      noticed. It is generally thought that alkyl chains serve as a stabilizer of the
      fullerene core units. Thus, a longer chain or higher plasticity of the
      stabilizers would promote the disturbance of the core-core interactions. It was
      indeed shown that longer alkyl chains resulted in a lower fluid viscosity. It was
      also found that metastable solid phases were produced by the noticeable van der
      Waals interaction between the long alkyl chains especially when a symmetric C60
      core was adopted. This interesting finding enabled the comparison of
      electrochemical activities of the C60 unit between the solvent-free liquid and
      metastable solid form, which revealed a superior electrochemical activity in the
      liquid state.

PMID- 23547958
TI  - Differences between sporadic and MEN related primary hyperparathyroidism;
      clinical expression, preoperative workup, operative strategy and follow-up.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is most commonly sporadic (sPHPT).
      However, sometimes PHPT develops as part of multiple endocrine neoplasia (MEN)
      type 1 or 2A. In all, parathyroidectomy is the only curative treatment.
      Nevertheless, there are important differences in clinical expression and
      treatment. METHODS: We analyzed a consecutive cohort of patients treated for
      sporadic, MEN1-related, and MEN2A-related PHPT and compared them regarding
      clinical and biochemical parameters, differences in preoperative workup,
      operative strategies, findings, and outcome. RESULTS: A total of 467 patients
      with sPHPT, 52 with MEN1- and 16 with MEN2A-related PHPT were analyzed. Patients
      with sPHPT were older, more often female and had higher preoperative calcium and
      parathyroid hormone levels, when compared with MEN1 and MEN2A patients. Minimally
      invasive parathyroidectomy (MIP) was performed in 367 of 467 sPHPT patients
      (79%). One abnormal parathyroid was found in 426 patients (91%). Two or more in
      35 patients (7%). In six patients (1%) no abnormal parathyroid gland was
      retrieved. Of 52 MEN1 patients, eight (15%) underwent a MIP and 44 patients (85%)
      underwent conventional neck exploration (CNE); with resection of fewer than 31/2
      enlarged glands in 21 patients (40%), subtotal parathyroidectomy (SPTX, 3-31/2
      glands) in seventeen (33%) and total parathyroidectomy with autotransplantation
      (TPTX) in six (12%). Eleven patients (21%) had persistent disease, 29 (56%)
      recurrent PHPT and nine (17%) permanent hypoparathyroidism, mostly after TPTX. Of
      16 MEN2A patients, six (38%) underwent MIP, four (25%) CNE and six (38%)
      selective resection of the enlarged gland(s) during total thyroidectomy. Three
      patients (19%) suffered from persistent PHPT and two (13%) developed recurrent
      disease. CONCLUSIONS: Sporadic PHPT, MEN1- and MEN2A-related PHPT are three
      distinct entities as is reflected preoperatively by differences in gender, age at
      diagnosis and calcium and PTH levels. MEN2A patients are very similar to sPHPT
      with respect to operative approach and findings. MIP is the treatment of choice
      for both. MIP has low rates of persistent and recurrent PHPT and a low
      complication rate. The percentage of multiglandular disease and recurrences are
      significantly higher in MEN1 patients, demonstrating the need for a different
      approach. We advocate treating these patients with CNE and SPTX.

PMID- 23547960
TI  - Advances in stem cell therapy for myocardial regeneration.

PMID- 23547959
TI  - Effect of working characteristics and taught ergonomics on the prevalence of
      musculoskeletal disorders amongst dental students.
AB  - BACKGROUND: Work-related musculoskeletal disorders are one of the main
      occupational health hazards affecting dental practitioners. This study was
      conducted to assess the prevalence of Work-related Musculoskeletal Disorder
      (WMSD) amongst dental students. Possible correlations with the working
      environment and ergonomics taught in Malaysian dental schools were also sought.
      METHODS: Five dental schools in Malaysia participated in this cross-sectional
      study. A validated self-administered questionnaire was used to establish the
      point prevalence of WMSD in the dental students based on various body regions.
      The questionnaire also collected data regarding the working environment, clinical
      practice and the taught ergonomics of the students during their training years.
      RESULTS: Out of five hundred and sixty eight dental students who participated in
      the study, 410 were in their clinical years whilst 158 were students in their non
      clinical years. Ninety three percent of the clinical year students reported
      symptoms of WMSD in one or more body regions. Female students reported a
      significantly higher numbers of symptoms compared to male students. The neck
      (82%) and lower back (64%) were reported to have the highest prevalence of WMSD.
      Discomfort in the neck region was found to be associated with self-reported
      frequency of bending of the neck. A majority of students (92%) reported minimum
      participation in workshops related to ergonomics in dentistry and 77% were
      unfamiliar with treatment and remedies available in the case of WMSD.
      CONCLUSIONS: There was more WMSD seen in dental students who had started their
      clinical years. Neck and lower back are more injury prone areas and are at
      increased risk of developing musculoskeletal disorders. Theory and practice of
      ergonomics should be incorporated into the dental undergraduate curriculum.

PMID- 23547961
TI  - Tracking the mesenchymal stem cell fate after transplantation into the infarcted
      myocardium.
AB  - Numerous studies have previously shown the efficiency of stem cell therapy in
      recovering the infarcted myocardium, by reducing the infarct size and improving
      the overall global function. However, the functional improvements observed in
      almost all cases were short-termed and many clinical trials showed that there
      were no long term relevant differences between infarcted myocardium with and
      without cell transplant. Moreover, studies monitoring cell engraftment after
      transplantation reported that cells were poorly retained into the heart and their
      large majority died posttransplantation, thus explaining the transient nature of
      the improvements. In these settings, it is likely that the improvement in the
      cardiac function is not due to the myocardial structure regeneration but rather
      to the biomolecules secreted by stem cells, which can improve the ventricular
      remodelling by attenuating the inflammation and promoting vascularisation and
      cell survival. This conclusion has prompted a re-consideration of stem cell field
      and imposed the stringency of understanding how stem cells respond to the host
      environment and differentiate toward a specific cell phenotype. This review is
      focused on the behaviour of mesenchymal stem cells after transplantation into the
      myocardial infarction and the molecular changes appeared in the infarcted
      environment that complicate the cross-talk between transplanted and host cells.

PMID- 23547963
TI  - Mesenchymal stem cells: promising for myocardial regeneration?
AB  - The pandemic of cardiovascular disease is continuously expanding as the result of
      changing life styles and diets throughout the Old and New World. Immediate
      intervention therapy saves the lives of many patients after acute myocardial
      infarction (MI). However, for many this comes at the price of adverse cardiac
      remodeling and heart failure. Currently, no conventional therapy can prevent the
      negative aftermath of MI and alternative treatments are warranted. Therefore,
      cardiac stem cell therapy has been put forward over the past decade, albeit with
      modest successes. Mesenchymal Stem Cells (MSC) are promising because these are
      genuine cellular factories of a host of secreted therapeutic factors. MSC are
      obtained from bone marrow or adipose tissue (ADSC). However, the heart itself
      also contains mesenchymal- like stem cells, though more difficult to acquire than
      ADSC. Interestingly, mesenchymal cells such as fibroblasts can be directly or
      indirectly reprogrammed to all myocardial cell types that require replacement
      after MI. To date, the paracrine and juxtacrine mechanisms of ADSC and other MSC
      on vessel formation are best understood. The preconditioning of, otherwise naive,
      stem cells is gaining more interest: previously presumed deleterious stimuli such
      as hypoxia and inflammation, i.e. causes of myocardial damage, have the opposite
      effect on mesenchymal stem cells. MSC gain a higher therapeutic capacity under
      hypoxia and inflammatory conditions. In this review, mesenchymal stem cells and
      their working mechanisms are put into the perspective of clinical cardiac stem
      cell therapy.

PMID- 23547962
TI  - Chemokine contribution in stem cell engraftment into the infarcted myocardium.
AB  - Modern life styles have made cardiovascular disease the leading cause of
      morbidity and mortality worldwide. Although current treatments substantially
      ameliorate patients' prognosis after MI, they cannot restore the affected tissue
      or entirely re-establish organ function. Therefore, the main goal of modern
      cardiology should be to design strategies to reduce myocardial necrosis and
      optimize cardiac repair following MI. Cell-based therapy was considered a novel
      and potentially new strategy in regenerative medicine; however, its clinical
      implementation has not yielded the expected results. Chemokines seem to increase
      the efficiency of cell-therapy and may represent a reliable method to be
      exploited in the future. This review surveys current knowledge of cell therapy
      and highlights key insights into the role of chemokines in stem cell engraftment
      in infarcted myocardium and their possible clinical implications.

PMID- 23547964
TI  - Stem cell regenerative potential combined with nanotechnology and tissue
      engineering for myocardial regeneration.
AB  - The stem cell-based therapy for post-infarction myocardial regeneration has been
      introduced more than a decade ago, but the functional improvement obtained is
      limited due to the poor retention and short survival rate of transplanted cells
      into the damaged myocardium. More recently, the emerging nanotechnology concepts
      for advanced diagnostics and therapy provide promising opportunities of using
      stem cells for myocardial regeneration. In this paper will be provided an
      overview of the use of nanotechnology approaches in stem cell research for: 1)
      cell labeling to track the distribution of stem cells after transplantation, 2)
      nanoparticle-mediated gene delivery to stem cells to promote their homing,
      engraftment, survival and differentiation in the ischemic myocardium and 3)
      obtaining of bio-inspired materials to provide suitable myocardial scaffolds for
      delivery of stem cells or stem cell-derived factors.

PMID- 23547965
TI  - Evaluation of gene and cell-based therapies for cardiac regeneration.
AB  - Although the treatment of acute myocardial infarction has improved considerably
      and the mortality rate is reduced, patients who survive may develop loss of
      cardiomyocytes, scar formation, ventricular remodeling, and ultimately heart
      failure. The treatment of the most severe types of heart failure is heart
      transplantation, but this therapeutic intervention is not available for a large
      number of patients due to a shortage of donor hearts. Since current
      pharmacological and interventional approaches are unsuccessful to regenerate
      infarcted myocardium, new approaches like gene- or cell-based therapies are
      tested to prevent loss of cardiac tissue, enhance angiogenesis, and to reduce
      left ventricular remodeling. Exciting and promising data on laboratory animals
      have moved the field rapidly into clinical trials. Although several clinical
      trials proved the safety and feasibility of using gene- and cell-based therapies,
      many challenges remain before large-scale novel treatment modules will be
      available. The purpose of this review is to summarize the key findings of larger,
      randomized clinical trials in cardiovascular medicine using both gene and cell
      based therapy, and to emphasize the most significant questions that emerged from
      the clinical experience so far, such as the optimal gene or cell type to be used,
      the ideal delivery route, and for DNA the ideal delivery system. Understanding
      the mechanisms of gene- and cell-based therapies is essential for designing the
      next phase clinical studies in the field of regenerative medicine.

PMID- 23547966
TI  - Stimulation of ovarian stem cells by follicle stimulating hormone and basic
      fibroblast growth factor during cortical tissue culture.
AB  - BACKGROUND: Cryopreserved ovarian cortical tissue acts as a source of primordial
      follicles (PF) which can either be auto-transplanted or cultured in vitro to
      obtain mature oocytes. This offers a good opportunity to attain biological
      parenthood to individuals with gonadal insufficiency including cancer survivors.
      However, role of various intra- and extra-ovarian factors during PF growth
      initiation still remain poorly understood. Ovarian biology has assumed a
      different dimension due to emerging data on presence of pluripotent very small
      embryonic-like stem cells (VSELs) and ovarian germ stem cells (OGSCs) in ovary
      surface epithelium (OSE) and the concept of postnatal oogenesis. The present
      study was undertaken to decipher effect of follicle stimulating hormone (FSH) and
      basic fibroblast growth factor (bFGF) on the growth initiation of PF during organ
      culture with a focus on ovarian stem cells. METHODS: Serum-free cultures of
      marmoset (n=3) and human (young and peri-menopausal) ovarian cortical tissue
      pieces were established. Cortical tissue pieces stimulated with FSH (0.5 IU/ml)
      or bFGF (100 ng/ml) were collected on Day 3 for histological and molecular
      studies. Gene transcripts specific for pluripotency (Oct-4A, Nanog), early germ
      cells (Oct-4, c-Kit, Vasa) and to reflect PF growth initiation (oocyte-specific
      Gdf-9 and Lhx8, and granulosa cells specific Amh) were studied by q-RTPCR.
      RESULTS: A prominent proliferation of OSE (which harbors stem cells) and
      transition of PF to primary follicles was observed after FSH and bFGF treatment.
      Ovarian stem cells were found to be released on the culture inserts and retained
      the potential to spontaneously differentiate into oocyte-like structures in
      extended cultures. q-RTPCR analysis revealed an increased expression of gene
      transcripts specific for VSELs, OGSCs and early germ cells suggestive of
      follicular transition. CONCLUSION: The present study shows that both FSH and bFGF
      stimulate stem cells present in OSE and also lead to PF growth initiation. Thus
      besides being a source of PF, cryopreserved ovarian cortical tissue could also be
      a source of stem cells which retain the ability to spontaneously differentiate
      into oocyte-like structures in vitro. Results provide a paradigm shift in the
      basic understanding of FSH action and also offer a new perspective to the field
      of oncofertility research.

PMID- 23547967
TI  - Nylon-3 polymers with selective antifungal activity.
AB  - Host-defense peptides inhibit bacterial growth but show little toxicity toward
      mammalian cells. A variety of synthetic polymers have been reported to mimic this
      antibacterial selectivity; however, achieving comparable selectivity for fungi is
      more difficult because these pathogens are eukaryotes. Here we report nylon-3
      polymers based on a novel subunit that display potent antifungal activity (MIC =
      3.1 MUg/mL for Candida albicans ) and favorable selectivity (IC10 > 400 MUg/mL
      for 3T3 fibroblast toxicity; HC10 > 400 MUg/mL for hemolysis).

PMID- 23547968
TI  - CAMTA 1 regulates drought responses in Arabidopsis thaliana.
AB  - BACKGROUND: Transcription factors (TF) play a crucial role in regulating gene
      expression and are fit to regulate diverse cellular processes by interacting with
      other proteins. A TF named calmodulin binding transcription activator (CAMTA) was
      identified in Arabidopsis thaliana (AtCAMTA1-6). To explore the role of CAMTA1 in
      drought response, the phenotypic differences and gene expression was studied
      between camta1 and Col-0 under drought condition. RESULTS: In camta1, root
      development was abolished showing high-susceptibility to induced osmotic stress
      resulting in small wrinkled rosette leaves and stunted primary root. In camta1
      under drought condition, we identified growth retardation, poor WUE, low
      photosystem II efficiency, decline in RWC and higher sensitivity to drought with
      reduced survivability. The microarray analysis of drought treated camta1 revealed
      that CAMTA1 regulates "drought recovery" as most indicative pathway along with
      other stress response, osmotic balance, apoptosis, DNA methylation and
      photosynthesis. Interestingly, majority of positively regulated genes were
      related to plasma membrane and chloroplast. Further, our analysis indicates that
      CAMTA1 regulates several stress responsive genes including RD26, ERD7, RAB18,
      LTPs, COR78, CBF1, HSPs etc. and promoter of these genes were enriched with CAMTA
      recognition cis-element. CAMTA1 probably regulate drought recovery by regulating
      expression of AP2-EREBP transcription factors and Abscisic acid response.
      CONCLUSION: CAMTA1 rapidly changes broad spectrum of responsive genes of membrane
      integrity and photosynthetic machinery by generating ABA response for challenging
      drought stress. Our results demonstrate the important role of CAMTA1 in
      regulating drought response in Arabidopsis, thus could be genetically engineered
      for improving drought tolerance in crop.

PMID- 23547969
TI  - Predictors of sexual abstinence among Wolaita Sodo University Students, South
      Ethiopia.
AB  - BACKGROUND: It is over 30 years since the first case of AIDS [Acquired Immune
      Deficiency Syndrome] was identified. Attention has been focused recently on the
      promotion of the "ABCs" of HIV prevention (being abstinent or delaying sex,
      remaining faithful to one sexual partner, and using condoms consistently during
      sexual intercourse). As programs that focus on ABCs to prevent heterosexual
      transmission HIV are rolled out, questions of how well university students who
      come from varied cultural contexts actually understand the terms and address
      challenges to adopt behaviors is unanswered. In Ethiopia, despite the mushrooming
      number of students in the higher learning institutions with the current figure
      being 210,000 students accommodated in 33 public and 72 private higher learning
      institutions, sexual and reproductive health services, are not delivered in an
      organized way. The objective of this study is to identify factors associated with
      Sexual abstinence among Wolaita Sodo University students to provide evidence for
      designing appropriate interventions. METHODS: A Cross-Sectional study was
      conducted among 750 undergraduate students selected from Wolaita Sodo University
      using a stratified simple random sampling technique during the academic year.
      Data were collected using structured self administered questionnaire, focus group
      discussion and in depth interview guides as tools for data collection. Ethical
      clearance was obtained from Jimma University and informed consent was obtained
      from the participants after explaining purpose of study. Statistical tests were
      employed wherever necessary at the significance level of 0.05. RESULTS: All of
      the participants had heard about HIV/AIDS of which 97.3% had good knowledge.
      Higher proportions of male students were sexually active than their counter
      parts. Students with better knowledge on HIV AIDS were 6.6 (95%CI=1.6, 12.9)
      times more likely to abstain from sexual intercourse than their counter parts.
      CONCLUSIONS: Knowledge of students about risk of HIV infection is strong
      predictors of sexual abstinence of students which were less observed among
      students who came from rural areas. The university needs to intensify strong
      behavior change communication using multiple strategies through the active
      involvement of students themselves within the university's premises and in the
      surrounding community in collaboration with stakeholders to promote Sexual
      abstinence.

PMID- 23547971
TI  - The long-term effects of a primary care physical activity intervention on mental
      health in low-active, community-dwelling older adults.
AB  - OBJECTIVES: To examine the effect that physical activity delivered via two
      different versions of the Green Prescription (a primary care physical activity
      scripting program) had on depressive symptomatology and general mental health
      functioning over a 12-month period in non-depressed, low-active, community
      dwelling older adults. METHOD: Two hundred and twenty-five participants from the
      Healthy Steps study took part in the present study. Healthy Steps participants
      were randomized to receive either the standard time-based or a modified pedometer
      based Green Prescription. Depression, mental health functioning and physical
      activity were measured at baseline, post-intervention (3 months post-baseline)
      and at the 9-month follow-up period. RESULTS: At post-intervention, a positive
      association was found between increases in leisure-time physical activity and
      total walking physical activity and a decrease in depressive symptomatology
      (within the non-depressed range of the GDS-15) and an increase in perceived
      mental health functioning, regardless of intervention allocation. These
      improvements were also evident at the follow-up period for participants in both
      intervention allocation groups. CONCLUSION: Our findings suggest that the
      standard time-based Green Prescription and a modified pedometer-based Green
      Prescription are both effective in maintaining and improving mental health in non
      depressed, previously low-active older adults.

PMID- 23547972
TI  - Optical spectral fingerprints of tissues from patients with different breast
      cancer histologies using a novel fluorescence spectroscopic device.
AB  - The fluorescence of paired human breast malignant and normal tissue samples was
      investigated using a novel fluorescence spectroscopic (S3-LED) ratiometer unit
      with no moving parts. This device can measure the emission spectra of key native
      organic biomolecules such as tryptophan, tyrosine, collagen and elastin within
      tissues by using LED (light emitting diode) excitation sources coupled to an
      optical fiber. With this device, the spectral profiles of 11 paired breast
      cancerous and normal samples from 11 patients with breast carcinoma were
      obtained. In each of the 11 cases, marked increases in the tryptophan levels were
      found in the breast carcinoma samples when compared to the normal breast tissues.
      In the breast cancer samples, there were also consistently higher ratios of the
      340 to 440 nm and the 340 to 460 nm intensity peaks after 280 nm excitation,
      likely representing an increased tryptophan to NADH ratio in the breast cancer
      samples. This difference was seen in the spectral profiles of the breast cancer
      patients regardless of whether they were HER2 positive or negative or hormone
      receptor positive or negative, and was found regardless of menopausal status,
      histology, stage, or tumor grade. 

PMID- 23547970
TI  - The Hedgehog signalling pathway in breast development, carcinogenesis and cancer
      therapy.
AB  - Despite the progress achieved in breast cancer screening and therapeutic
      innovations, the basal-like subtype of breast cancer (BLBC) still represents a
      particular clinical challenge. In order to make an impact on survival in this
      type of aggressive breast cancer, new targeted therapeutic agents are urgently
      needed. Aberrant activation of the Hedgehog (Hh) signalling pathway has been
      unambiguously tied to cancer development and progression in a variety of solid
      malignancies, and the recent approval of vismodegib, an orally bioavailable small
      molecule inhibitor of Smoothened, validates Hh signalling as a valuable
      therapeutic target. A number of recent publications have highlighted a role for
      Hh signalling in breast cancer models and clinical specimens. Interestingly, Hh
      ligand overexpression is associated with the BLBC phenotype and a poor outcome in
      terms of metastasis and breast cancer-related death. In this review, we provide a
      comprehensive overview of the canonical Hh signalling pathway in mammals,
      highlight its roles in mammary gland development and breast carcinogenesis and
      discuss its potential therapeutic value in BLBC. 

PMID- 23547973
TI  - Collagen-hydroxyapatite/cisplatin drug delivery systems for locoregional
      treatment of bone cancer.
AB  - In this paper, the synthesis and characterization of novel cisplatin-loaded
      collagen (COLL)/hydroxyapatite (HA) composite materials are presented. The
      composite materials were designed to obtain a COLL: HA weight ratio close to the
      bone composition. The content of embedded cisplatin was chosen to assure a
      concentration of cisplatin of 6 and 10 MUM, respectively, into the culture media
      used in cell culture experiments. These cisplatin delivery systems were
      characterized by determining the physico-chemical properties of the composite
      material, the drug release process as well as their biological activity. Based on
      the in vitro data that showed the cytotoxic, anti-proliferative and anti-invasive
      activities of these multifunctional systems on G292 osteosarcoma cells in
      dependence on the cisplatin concentration released in culture medium, we conclude
      that the newly developed COLL/HA-cisplatin drug delivery system could be a
      feasible approach for locoregional chemotherapy of bone cancer. 

PMID- 23547975
TI  - Drug embedded PVP coated magnetic nanoparticles for targeted killing of breast
      cancer cells.
AB  - Magnetic drug targeting is a drug delivery system that can be used in loco
      regional cancer treatment. Coated magnetic particles, called carriers, are very
      useful for delivering chemotherapeutic drugs. Magnetic carriers were synthesized
      by co-precipitation of iron oxide followed by coating with polyvinyl pyrrolidone
      (PVP). Characterization was performed using X-ray diffraction, TEM, TGA, FTIR and
      UV-Vis Spectroscopy. Magnetite (Fe3O4) remained as the core of the carrier. The
      amount of PVP bound to the iron oxide nanoparticles was estimated by
      thermogravimetric analysis (TGA) and the attachment of PVP to the iron oxide
      nanoparticles confirmed by FTIR analysis. The loading efficiency of Epirubicin
      hydrochloride onto the PVP coated and uncoated iron oxide nanoparticles was
      measured at intervals such as 1 hr and 24 hrs by UV-Vis Spectroscopy. The binding
      of Epirubicin hydrochloride to the PVP coated and uncoated iron oxide
      nanoparticles were confirmed by FTIR analysis. The present findings showed that
      Epirubicin hydrochloride loaded PVP coated iron oxide nanoparticles are promising
      for magnetically targeted drug delivery. The drug displayed increased cell
      cytotoxicity at lower concentrations when conjugated with the nanoparticles than
      being administered conventionally as individual drugs. 

PMID- 23547974
TI  - Acute hematologic and mucosal toxicities in head and neck cancer patients
      undergoing chemoradiotherapy: a comparison of 3D-CRT, IMRT, and helical
      tomotherapy.
AB  - IMRT and helical tomotherapy for head and neck cancer (HNC) treatment are
      associated with higher doses to certain non-target tissues than traditional
      static beam techniques. We hypothesized that this may lead to higher acute
      mucosal and hematologic toxicities. This analysis was limited to 178 patients
      receiving >=60 Gy with concurrent weekly cisplatin. Radiation delivery used 3D
      CRT in 41 patients (23%), conventional IMRT in 56 patients (31%), and helical
      tomotherapy in 81 patients (46%). Acute mucositis rates, weekly hematologic
      parameters, and ability to deliver planned chemotherapy cycles were examined for
      each patient during their course of chemoradiotherapy. Analysis showed patients
      were well balanced with regard to sex, age, and stage. Treatment time, as
      assessed by delivered monitor units, varied significantly between the 3D-CRT
      (median = 502), IMRT (median = 1087), and tomotherapy (median = 6757) cohorts.
      Acute mucositis grades did not significantly differ between the three subsets.
      Through six weeks of chemoradiotherapy, the median decline in hemoglobin was
      15.6%, the median decline in platelets was 30.6%, and the median decline in
      leukocytes was 51.5%, but these drops were not significantly different between
      treatment cohorts. Chemotherapy was discontinued or held secondary to hematologic
      toxicity in 12% of 3D-CRT patients, 5% of IMRT patients and 15% of tomotherapy
      patients (p = 0.14). In conclusion, HNC patients undergoing high dose radiation
      with concurrent weekly cisplatin chemotherapy, the longer beam-on times and
      larger volumes of low-to-moderate radiation doses to non-target tissues
      associated with modern IMRT delivery techniques do not appear to result in
      increased acute hematologic or mucosal toxicities. 

PMID- 23547976
TI  - Can a belly board reduce respiratory-induced prostate motion in the prone
      position?--assessed by cine-magnetic resonance imaging.
AB  - The purpose of this study is to evaluate the real-time respiratory motion of the
      prostate and surrounding tissues/organs in the supine and prone positions and to
      investigate, using cine-MRI, whether a belly board can reduce respiratory-induced
      motion in the prone position. Cine-MRI scans were made of 13 volunteers in the
      supine and prone positions on a flat board and in two different prone positions
      using a belly board. Images in cine mode were recorded for 20 seconds. For each
      session, the points of interest (POIs) were located at the apex, base, mid
      anterior surface and mid-posterior surface of the prostate; the tip of the
      seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and
      standard deviation (SD) of the displacement from the mean value were calculated.
      The SDs for each of the four different positions were compared using a paired t
      test. Respiratory-induced prostate motion was significantly larger in the prone
      position than in the supine position. However, when a belly board was used in the
      prone position, motion in the prostate and surrounding tissues/organs was
      significantly reduced. There were no significant differences between the two
      different positions using a belly board in any of the POIs. 

PMID- 23547978
TI  - LT2 Cryptosporidium data: what do they tell us about Cryptosporidium in surface
      water in the United States?
AB  - Beginning in 2006 a United States Federal regulation required public water
      suppliers using surface water serving more than 10,000 population to analyze for
      Cryptosporidium in at least 24 consecutive monthly samples from each surface
      water source. In July 2012, the U.S. EPA released the resulting data consisting
      of ca. 45,000 records. No Cryptosporidium were found in 93% of samples and no
      Cryptosporidium were found in any samples analyzed from over half of 1670
      locations sampled. Nevertheless, at 250 locations representing every region of
      the U.S., Cryptosporidium were found in sufficient numbers of samples to provide
      a picture of their occurrence nationwide. Data from about 100 sites reporting the
      highest numbers were examined in detail. Although analysis of matrix spikes was
      required for quality control, the results do not permit estimating organism
      concentrations. The data reported at each of the individual sample locations were
      analyzed in the form of cumulative probability distributions to describe key risk
      related features of median level and variability. Taken as a whole, the data
      describe a spectrum of median Cryptosporidium occurrence in surface waters of the
      U.S. ranging from ca. 0.005 to ca. 0.5 oocysts/L. The variability at individual
      sites ranged from ca. 1 to 15 r.s.d. Based on the LT2 positive data, comparison
      to measurements of other water quality parameters, and independent means of
      estimating organism production from watersheds reported in the literature, the
      hypothesis is offered that Cryptosporidium may be found in surface water anywhere
      worldwide continuously and within the spectrum defined above.

PMID- 23547977
TI  - Tomotherapy radiosurgery for arteriovenous malformations--current possibilities
      and future options with helical tomotherapy dynamic jaws?
AB  - This planning study was performed to compare stereotactic linac based
      radiosurgery of Arteriovenous Malformations (AVM) with current Helical
      Tomotherapy (HT) and future HT techniques. For 10 patients with AVM, dose
      distributions and treatment times of "regular" HT delivery (Reg 2.5/1/0.6 cm
      field width), Running-Start-Stop Treatment (RSS 5/2.5 cm), Axial Mode (Axial 5
      cm) and Dynamic Jaw/Dynamic Couch delivery with a maximum field width of 5 cm
      (DJDC 5) were analysed and compared to linac-based stereotactic radiosurgery.
      Axial produced the fastest treatment (Axial 4:47 min vs. Linac 32:42 min) at the
      cost of large brain exposure (V10% 289 ml). Except for Reg 0.6, all other HT
      techniques achieved significantly shorter treatment times than linac-based
      treatment (e.g. Reg 1, 19:42 min, DJDC 6:30 min). However, high-dose brain
      exposure (V60%) was higher in all HT plans (e.g. Reg 0.6, 10 ml, Linac 9 ml), and
      only Reg 0.6 showed better low-dose exposure (V10% of 167 ml vs. 199 ml, not
      significant). Neither current nor future HT modes in their current version
      outperformed linac-based stereotactic radiosurgery. However, AVM with special
      geometry might still benefit from HT.

PMID- 23547979
TI  - Color obsessions and phobias in autism spectrum disorders: the case of J.G.
AB  - The current study is the first investigation of color 'obsessions' and 'phobias'
      in ASD. We investigate the color perception and cognition of J.G., a boy with ASD
      who has a strong obsession with blue, and a strong phobia of other colors. J.G.'s
      performance on a series of color tasks (color-entity association; chromatic
      discrimination; color classification) is compared to 13 children with and without
      autism who do not have color obsessions or phobias. The findings lead to the
      formalization of two hypotheses: (i) color obsessions and phobias in individuals
      with ASD are related to an unusually strong ability to associate colors with
      entities; (ii) color obsessions are related to hyposensitivity, and color phobias
      to hypersensitivity, in the affected regions of color space. 

PMID- 23547980
TI  - Comparative measurement of CNP and NT-proCNP in human blood samples: a
      methodological evaluation.
AB  - BACKGROUND: C-type natriuretic peptide (CNP) has anti-inflammatory, anti
      proliferative, and anti-migratory properties. During the past years, CNP has
      attained an increasing interest by many research groups, especially in the
      cardiovascular field. Nevertheless, still no reliable data exist on the
      difference of CNP concentration between serum and plasma samples. Also, the
      influence of delayed blood sample proceeding is unknown. The aim of this study
      was to investigate the difference of CNP and NT-proCNP concentrations between
      serum and plasma samples. In order to identify potential methodological bias,
      this study should also validate the stability of CNP and NT-proCNP in full blood
      samples stored at room temperature. FINDINGS: Triplets (serum, plasma, full
      blood) of fasting blood samples from 12 healthy male individuals were collected.
      Analysis of CNP and NT-proCNP concentration was performed immediately following
      sampling, and after 30 minutes or 2 hours of storage at room temperature. Mean
      serum concentrations at baseline were 0.997 +/- 0.379 ng/ml for CNP and 58.5 +/-
      28.3 pg/ml for NT-proCNP. Furthermore, NT-proCNP concentration did not change
      significantly during the allotted time and did not differ between serum, plasma,
      and full blood samples. At baseline, concentrations of CNP were significantly
      different between samples containing either sodium-citrate or EDTA as a clotting
      inhibitor (1.933 +/- 0.699 ng/ml vs. 0.991 +/- 0.489 ng/ml, p = 0.001).
      CONCLUSIONS: CNP and NT-proCNP are stable for at least two hours, even when
      sample processing is delayed or blood probes are stored at room temperature. NT
      proCNP assay demonstrated more consistent and reliable data and should therefore
      be preferred for usage in clinical applications. Nevertheless, as recommended for
      ANP and BNP, immunoassays for CNP should also be standardized or harmonized in
      the future.

PMID- 23547981
TI  - Hemodialysis and hemodiafiltration differently modulate left ventricular
      diastolic function.
AB  - BACKGROUND: Renal replacement therapy may have a favorable effect on diastolic
      left ventricular function, but it is not clear whether hemodiafiltration is
      superior to hemodialysis in this field. Nitric oxide (NO) and asymmetric
      dimethylarginine (ADMA) may play a role in the changes of intracardiac
      hemodynamics, but it is not clear whether the different renal replacement methods
      have disparate influence on the metabolism of these materials. METHODS: Thirty
      patients on renal replacement therapy were investigated. First, data was analyzed
      while patients received hemodiafiltration over a period of three months. Then,
      the same patients were evaluated during treatment with hemodialysis for at least
      another three months. Echocardiography was performed before and after renal
      replacement therapy. RESULTS: No significant difference was found in the volume
      removals between hemodialysis and hemodiafiltration. The left atrial diameter and
      transmitral flow velocities (E/A) decreased significantly only during
      hemodiafiltration. A positive correlation was observed between the left atrial
      diameter and E/Ea representing the left ventricular pressure load during
      hemodiafiltration. Significant correlations between NO and A and E/A were
      observed only in the case of hemodiafiltration. CONCLUSION: Hemodiafiltration has
      a beneficial effect on echocardiographic markers representing left ventricular
      diastolic function. This could be attributed to the differences between the
      dynamics of volume removal and its distribution among liquid compartments.

PMID- 23547982
TI  - Investigating the structural dependence of protein stabilization by amino acid
      substitution.
AB  - A goal of protein engineering technology is developing methods to increase
      protein stability. However, rational design of stable proteins is difficult
      because the stabilization mechanism of proteins is not fully understood. In this
      study, we examined the structural dependence of protein stabilization by
      introducing single amino acid substitution into ribonuclease H1 from the
      psychotropic bacterium Shewanella oneidensis MR-1 (So-RNase H1), which was our
      model protein. We performed saturation mutagenesis at various sites. Mutations
      that stabilized So-RNase H1 were screened using an RNase H-dependent temperature
      sensitive Escherchia coli strain. Stabilizing mutations were identified by the
      suppressor mutagenesis method. This method yielded 39 stabilized mutants from 513
      mutations at 27 positions. This suggested that more than 90% of mutations caused
      destabilization even in a psychotropic protein. However, 17 positions had
      stabilizing mutations, indicating that the stabilization factors were dispersed
      over many positions. Interestingly, the identified mutations were distributed
      mainly at exposed or nonconserved sites. These results provide a novel strategy
      for protein stabilization.

PMID- 23547983
TI  - Fabrication of tantalum and nitrogen codoped ZnO (Ta, N-ZnO) thin films using the
      electrospay: twin applications as an excellent transparent electrode and a field
      emitter.
AB  - The realization of stable p-type nitrogen-doped ZnO thin films with durable and
      controlled growth is important for the fabrication of nanoscale electronic and
      optoelectronic devices. ZnO thin films codoped with tantalum and nitrogen (Ta, N
      ZnO) were fabricated by using the electrospraying method at an atmospheric
      pressure. X-ray diffraction (XRD) studies demonstrated that all the prepared
      films were polycrystalline in nature with hexagonal wurtzite structure. In
      addition, a shift in the XRD patterns was observed, and the crystal orientation
      was changed at a certain amount of nitrogen (>6 at.%) in the starting solution.
      Analysis of X-ray diffraction patterns and X-ray photoelectron spectra revealed
      that nitrogen which was combined with the zinc atom (N-Zn) was successfully doped
      into the ZnO crystal lattice. It was also observed that 2 at.% tantalum and 6
      at.% nitrogen (2 at.% Ta and 6 at.% N) were the optimal dopant amounts to achieve
      the minimum resistivity of about 9.70 * 10(-5) Omega cm and the maximum
      transmittance of 98% in the visible region. Consequently, the field-emission
      characteristics of such a Ta, N-ZnO emitter can exhibit the higher current
      density of 1.33 mA cm(-2), larger field-enhancement factor (beta) of 4706, lower
      turn-on field of 2.6 V MUm(-1), and lower threshold field of 3.5 V MUm(-1)
      attributed to the enhanced conductivity and better crystallinity of films.
      Moreover, the obtained values of resistivity were closest to the lowest
      resistivity values among the doped ZnO films as well as to the indium tin oxide
      (ITO) resistivity values that were previously studied. We confirmed that the
      tantalum and nitrogen atoms substitution in the ZnO lattice induced positive
      effects in terms of enhancing the free carrier concentration which will further
      improve the electrical, optical, and field-emission properties. The proposed
      electrospraying method was well suitable for the fabrication of Ta, N-ZnO thin
      films at optimum conditions with superior electrical, optical, and field-emission
      characteristics, implying the potential applications as both a transparent
      electrode and field-emission (FE) devices.

PMID- 23547984
TI  - Scaling approach for intramolecular magnetic coupling constants of organic
      diradicals.
AB  - The intramolecular magnetic coupling constants (J) of 9 diradicals (i-ix) coupled
      with an aromatic ring were investigated by means of unrestricted density
      functional theory (DFT) calculations [UB3LYP/6-311++G(d,p)]. For these
      diradicals, a remarkable linear relationship between the calculated and
      experimental J values was found. In this study, we suggest that the slope (0.380)
      of the linear relationship can be utilized as a scaling factor for estimating J
      values. By applying this scaling factor and calculating J values, we could
      predict the reliable J values of four dithiadiazolyl (DTDA) diradicals coupled
      with an aromatic ring. It was also found that this scaling scheme shows a
      dependence on the length of a coupler. Nevertheless, this scaling approach could
      be used to estimate J values for diverse diradical systems coupled with a
      particular coupler by DFT calculations.

PMID- 23547985
TI  - Vitamin D and corticosteroids in asthma: synergy, interaction and potential
      therapeutic effects.

PMID- 23547987
TI  - Post-breast cancer radiotherapy bronchiolitis obliterans organizing pneumonia.
AB  - Post-radiotherapy bronchiolitis obliterans organizing pneumonia may occur in as
      many as 2.3% of women receiving radiation therapy for breast cancer. Cough and
      fever are common symptoms, and a quarter of these women have no symptoms. Latency
      period is usually within 6 months after completion of therapy but may be as long
      as 1 year. Pulmonary function is normal or will show slight decreases in vital
      capacity and diffusing capacity. Chest computed tomography studies show ground
      glass opacities with air bronchograms within and outside the radiation field, and
      there are often peripheral triangular-shaped infiltrates. Management consists of
      close monitoring of women who have no symptoms or minimal symptoms, and a short
      course of corticosteroid therapy for women who have symptoms and extensive
      bronchiolitis obliterans organizing pneumonia. The prognosis is excellent; there
      have been no deaths reported.

PMID- 23547988
TI  - The association between acetaminophen and asthma: should its pediatric use be
      banned?
AB  - During the last few decades, a huge epidemiological effort has been made all over
      the world in order to cast some light on the origin of asthma (or 'wheezing
      disorders' as a general term) and its recent increase in prevalence. The focus on
      genetic factors has failed to show any genetic signal strong enough to be
      seriously considered, and the tiny genetic signals found have never been
      appropriately replicated. The focus on environmental factors has provided some
      variable signals on the role of infections, allergens and bacterial substances,
      the direction of which have curiously varied from protecting to inducing asthma.
      The only environmental factor that has launched a large and consistent
      epidemiological signal, found in almost every epidemiological study addressing
      the issue, is previous acetaminophen exposure, which consistently increases the
      prevalence and clinical manifestations of every wheezing disorder under study. Is
      acetaminophen a real asthma promoter or an innocent bystander?

PMID- 23547989
TI  - Opioids for refractory dyspnea.
AB  - Refractory dyspnea is breathing difficulty that persists at rest or with minimal
      activity despite optimal therapy of the underlying condition. Both endogenous
      (beta-endorphin) and exogenous (morphine) opioids modulate the perception of
      dyspnea by binding to opioid receptors. Proposed mechanisms whereby opioids
      relieve refractory dyspnea include: decreasing respiratory drive with an
      associated decrease in corollary discharge; altering central perception; altering
      activity of peripheral opioid receptors located in the lung and decreasing
      anxiety. As patients respond variably to opioid therapy, a low dose of an opioid
      should be prescribed initially to manage refractory dyspnea. The dose should be
      titrated to achieve the lowest effective dose based on patient ratings of
      breathing difficulty. Research is needed to address clinical uncertainties and to
      identify genetic factors to improve the use of opioids to relieve refractory
      dyspnea.

PMID- 23547990
TI  - The role of desmosines as biomarkers for chronic obstructive pulmonary disease.
AB  - Since chronic obstructive pulmonary disease (COPD) has a progressive and major
      impact on health management, many aspects of this disorder, including development
      of effective and reliable biomarkers to monitor disease progression, are under
      intensive investigation. A huge amount of data, accumulated over the years, have
      provided solid evidence that two pyridinium-ring-containing amino acid isoforms,
      desmosine and isodesmosine (usually referred to as desmosines), unique to mature
      elastin in humans, are representative of the elastin breakdown occurring in
      chronic destructive disorders, such as COPD. This paper is aimed at providing a
      critical review of the methodological steps that have marked the progress in the
      detection of desmosines in biological fluids in health and disease, as well as
      the progress in the authors knowledge of desmosines' role in the pathophysiology
      of COPD. The authors have tried to emphasize that the suitability of desmosine as
      a biomarker for COPD increased over the years, as the techniques developed for
      its detection became progressively more sophisticated and precise. The authors
      conclude that desmosines, although not yet definitely proven, have nevertheless
      all the requisites to become a critical COPD biomarker.

PMID- 23547991
TI  - Streamlining antibiotic therapy with procalcitonin protocols: consensus and
      controversies.
AB  - Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate
      biomarker for likelihood and severity of bacterial infections. In community
      acquired pneumonia and other respiratory infections, PCT-guided antibiotic
      therapy algorithms resulted in reduced antibiotic exposure while maintaining a
      similar or even better level of safety compared with standard care. Reductions in
      antibiotic use translate into lower treatment costs, decreased risk of side
      effects and decreased bacterial multiresistance. This is especially important, as
      acute respiratory infections represent the most frequent reason for antibiotic
      prescriptions worldwide. Still, there is some controversy about the benefits of
      PCT measurement in sepsis patients in the intensive care unit and for
      nonrespiratory infections. Highly sensitive PCT assays are readily available in
      many hospitals today, and point-of-care assays with high enough sensitivity for
      antibiotic guidance are expected to be available soon. Herein, the authors
      provide an overview of recent studies evaluating PCT in different clinical
      situations and an outlook of currently enrolling or upcoming interventional
      trials.

PMID- 23547992
TI  - Carbon monoxide and cyanide toxicity: etiology, pathophysiology and treatment in
      inhalation injury.
AB  - Inhalation injury is most commonly associated with damage to the mucosal surfaces
      of the small and large airways after exposure to smoke and other products of
      incomplete combustion. Yet, there are far deadlier things lurking within the
      smoke than just the heat and particulate matter: carbon monoxide and cyanide.
      These two toxic substances are found in varying concentrations within the fire
      room and are associated with early on-scene death and in-hospital morbidity and
      mortality. Patients suffering from carbon monoxide and/or cyanide poisoning
      present with vague symptoms requiring an astute physician to make the diagnosis.
      Fortunately, the toxic effects related to exposure to these agents can be
      reversed with readily available antidotes.

PMID- 23547993
TI  - Overview and assessment of risk factors for pulmonary embolism.
AB  - Pulmonary embolism is one of the most common undiagnosed conditions affecting
      hospitalized patients. There are a plethora of risk factors for venous
      thromboembolism and pulmonary emboli. These factors are grouped under the broad
      triad of hypercoagulability, stasis and injury to provide a framework for
      understanding. Important risk factors include inherited thrombophilia, age,
      malignancy and estrogens. These risk factors are reviewed in detail and several
      risk assessment models are reviewed. These risk assessment models help identify
      those at risk for disease and therefore candidates for thromboprophylaxis.
      Diagnosis can be difficult and is aided by clinical decision rules that
      incorporate clinical scores that define the likelihood of pulmonary embolism.
      These are important considerations, not only for diagnostic purposes, but also to
      minimize excessive use of imaging, which increases exposure to and risks
      associated with radiation. A healthy index of suspicion is often the key to
      diagnosis.

PMID- 23547998
TI  - Ergonomics and sustainability.

PMID- 23547999
TI  - Immunosenescence in vertebrates and invertebrates.
AB  - There is an established consensus that it is primarily the adaptive arm of
      immunity, and the T cell subset in particular, that is most susceptible to the
      deleterious changes with age known as "immunosenescence". Can we garner any clues
      as to why this might be by considering comparative immunology and the
      evolutionary emergence of adaptive and innate immunity? The immune system is
      assumed to have evolved to protect the organism against pathogens, but the way in
      which this is accomplished is different in the innate-vs-adaptive arms, and it is
      unclear why the latter is necessary. Are there special characteristics of
      adaptive immunity which might make the system more susceptible to age-associated
      dysfunction? Given recent accumulating findings that actually there are age
      associated changes to innate immunity and that these are broadly similar in
      vertebrates and invertebrates, we suggest here that it is the special property of
      memory in the adaptive immune system which results in the accumulation of cells
      with a restricted receptor repertoire, dependent on the immunological history of
      the individual's exposures to pathogens over the lifetime, and which is commonly
      taken as a hallmark of "immunosenescence". However, we further hypothesize that
      this immunological remodelling per se does not necessarily convey a disadvantage
      to the individual (ie. is not necessarily "senescence" if it is not deleterious).
      Indeed, under certain circumstances, or potentially even as a rule, this
      adaptation to the individual host environment may confer an actual survival
      advantage.

PMID- 23548000
TI  - Homologues of bacterial TnpB_IS605 are widespread in diverse eukaryotic
      transposable elements.
AB  - BACKGROUND: Bacterial insertion sequences (IS) of IS200/IS605 and IS607 family
      often encode a transposase (TnpA) and a protein of unknown function, TnpB.
      RESULTS: Here we report two groups of TnpB-like proteins (Fanzor1 and Fanzor2)
      that are widespread in diverse eukaryotic transposable elements (TEs), and in
      large double-stranded DNA (dsDNA) viruses infecting eukaryotes. Fanzor and TnpB
      proteins share the same conserved amino acid motif in their C-terminal half
      regions: D-X(125, 275)-[TS]-[TS]-X-X-[C4 zinc finger]-X(5,50)-RD, but are highly
      variable in their N-terminal regions. Fanzor1 proteins are frequently captured by
      DNA transposons from different superfamilies including Helitron, Mariner, IS4
      like, Sola and MuDr. In contrast, Fanzor2 proteins appear only in some IS607-type
      elements. We also analyze a new Helitron2 group from the Helitron superfamily,
      which contains elements with hairpin structures on both ends. Non-autonomous
      Helitron2 elements (CRe-1, 2, 3) in the genome of green alga Chlamydomonas
      reinhardtii are flanked by target site duplications (TSDs) of variable length
      (approximately 7 to 19 bp). CONCLUSIONS: The phylogeny and distribution of the
      TnpB/Fanzor proteins indicate that they may be disseminated among eukaryotic
      species by viruses. We hypothesize that TnpB/Fanzor proteins may act as
      methyltransferases.

PMID- 23548001
TI  - Identification of molecular processes needed for vascular formation through
      transcriptome analysis of different vascular systems.
AB  - BACKGROUND: Vascular system formation has been studied through molecular and
      genetic approaches in Arabidopsis, a herbaceous dicot that is used as a model
      system. Different vascular systems have developed in other plants such as crops
      and trees. Uncovering shared mechanisms underlying vascular development by
      transcriptome analysis of different vascular systems may help to transfer
      knowledge acquired from Arabidopsis to other economically important species.
      RESULTS: Conserved vascular genes and biological processes fundamental to
      vascular development were explored across various plants. Through comparative
      transcriptome analysis, 226 genes from Arabidopsis, 217 genes from poplar and 281
      genes from rice were identified as constituting 107 conserved vascular gene
      groups. These gene groups are expressed mainly in vascular tissues and form a
      complex coexpression network with multiple functional connections. To date, only
      half of the groups have been experimentally investigated. The conserved vascular
      gene groups were classified into 9 essential processes for vascular development.
      18 groups (17%) lack of annotations were classified as having unknown functions.
      CONCLUSION: The study provides a map of fundamental biological processes
      conserved across different vascular systems. It identifies gaps in the
      experimental investigation of pathways active in vascular formation, which if
      explored, could lead to a more complete understanding of vascular development.

PMID- 23548003
TI  - Probiotics for irritable bowel syndrome: should we give them full names?

PMID- 23548002
TI  - Timing of renal replacement therapy initiation by AKIN classification system.
AB  - INTRODUCTION: Previous studies using Acute Kidney Injury Network (AKIN)/RIFLE
      criteria to classify early initiation of renal replacement therapy (RRT) have
      defined it as the therapy started in less severe AKIN/RIFLE stages. Generally,
      these studies failed in demonstrating measurable benefits. METHODS: We compared
      RRT initiation in critically ill patients and defined early or late RRT in
      reference to timing after stage 3 AKIN was met: patients beginning RRT within 24
      hours after acute kidney injury (AKI) stage 3 were considered early starters.
      AKIN criteria were evaluated by both urine output (UO) and serum creatinine (sCr)
      and patients with acute-on-chronic kidney disease were excluded. A propensity
      score methodology was used to control variables. RESULTS: A total of 358
      critically ill patients were submitted to RRT. Only 150 patients with pure AKI at
      stage 3 were analyzed. Mortality was lower in the early RRT group (51.5 vs.
      77.9%, P=0.001). After achieving balance between the groups using a propensity
      score, there was a significant 30.5 (95% confidence interval [CI] 14.4 to 45.2%,
      P=0.002) relative decrease of mortality in the early RRT group. Moreover,
      patients on the early RRT group had lower duration of mechanical ventilation,
      time on RRT and a trend to lower intensive care unit (ICU) length of stay.
      CONCLUSIONS: For the first time, AKIN was used with UO criterion to evaluate
      early and late RRT. Using a time-based approach could be a better parameter to
      access the association between RRT initiation and outcomes in patients with AKI.

PMID- 23548004
TI  - Enterocutaneous fistulas and Crohn's disease: clinical characteristics and
      response to treatment.
AB  - INTRODUCTION: the low prevalence of enterocutaneous fistulas (ECF) in patients
      with Crohn's disease (CD) justifies the scarcity of studies that analyze the
      effect of medical treatment and the need for surgery in these patients. The
      objective of this study was to evaluate the clinical characteristics of patients
      with CD who have ECF and the response to different treatments. MATERIALS AND
      METHODS: patients with CD who presented ECF fistula between 1970 and 2009 in
      three tertiary centers in Spain were analyzed retrospectively for their clinical
      characteristics, response to treatment as well as the correlation between the
      response to biological therapies for ECF and perianal disease. The inflammatory
      activity of the disease was measured using the Harvey-Bradshaw index. The
      definitions of partial or complete response were based on the treating
      physician's judgment. RESULTS: twenty six patients were included (18 women); in
      more than half of cases (67%), anti-TNF treatment improved fistula drainage.
      Postoperative fistulas responded better to anti-TNF treatment than did
      spontaneous fistulas (80 versus 57%). One hundred percent and 60% of spontaneous
      and postoperative fistulas closed after surgery, respectively. CONCLUSIONS:
      although the majority of patients required surgery as the ultimate treatment,
      anti-TNF drugs improved fistula output in an acceptable percentage of patients
      who were treated. Therefore, this may be a treatment strategy prior to surgery in
      a select group of patients.

PMID- 23548005
TI  - Fully covered self-expanding metal stents in the management of difficult common
      bile duct stones.
AB  - BACKGROUND AND OBJECTIVES: plastic biliary stents are often used after an ERCP
      session without complete common bile duct stones (CBDS) extraction. Sometimes,
      the volume of biliary drainage with these stents may be insufficient. We present
      our experience with the use of fully covered self-expanding metal stents (FCSEMS)
      in the setting of incomplete CBDS extraction. PATIENTS AND METHODS: after an ERCP
      session with difficult CBDS not completely removed, biliary FCSEMS (Wallflex)
      were inserted in some patients when it was deemed that biliary sphincterotomy and
      a single plastic stent would not provide an adequate drainage. RESULTS: a
      retrospective study was performed. Biliary FCSEMS were inserted in 29 patients,
      mean age 81 years. CBDS could not be extracted through a biliary sphincterotomy
      due to its large size (n = 18) or because of the presence of inflammatory distal
      strictures (n = 11). The greatest biliary drainage with shortest ERCP time was
      considered mandatory due to clinical instability of patients and/or poor
      tolerance to conscious sedation administered by the endoscopist. Successful
      biliary drainage was obtained in all cases. FCSEMS were removed after a median of
      199.5 days in 16 patients with a complete CBDS extraction in 15 (93.7%). FCSEMS
      were not removed in the remaining 13 patients due to their clinical condition,
      and a wait-and-see strategy was undertaken. CONCLUSIONS: in selected cases,
      utilization of removable FCSEMS can be a good option for a quick and adequate
      biliary drainage in the setting of difficult CBDS. Because of the higher cost of
      these stents its use needs to be individualized.

PMID- 23548006
TI  - Impact of orocecal transit time on patient's perception of lactose intolerance.
AB  - BACKGROUND: symptoms attributed to the lactose intolerance are an important
      public health issue because of their prevalence and social relevance. Also
      because they may cause undue rejection of dairy products consume with potential
      health consequences. Transit time is a putative factor implied in the severity of
      symptoms associated with lactose. OBJECTIVES: to elucidate the relation between
      orocecal transit time (OCTT) and lactose intolerance symptoms. METHODS:
      observational study in patients referred to a lactose hydrogen breath test who
      showed an increase in breath H2 excretion higher than 25 ppm. OCTT was measured
      with the breath test and symptoms of lactose tolerance with a validated scale.
      Symptoms were measured twice: before receiving the lactose, inquiring about self
      perceived symptoms when patients consumed dairy products at home ("home
      symptoms"), and again after completing the lactose breath test ("test symptoms").
      RESULTS: 161 patients were included. There was no correlation between OCTT and
      home symptoms (r = -0.1). When OCTT was faster than 60 minutes, intensity of
      "test symptoms" was similar to "home symptoms". However, in patients with normal
      or slow OCTT, the "home symptoms" were more intense than the "test symptoms" (p <
      0.05). At home, symptoms were independent of OCTT but with the lactose test load
      the symptoms were proportionately more intense with faster OCTT. CONCLUSIONS: in
      lactose maldigesters, selfreported symptoms of lactose intolerance are more
      pronounced at home than after a high lactose challenge. Intolerance symptoms that
      patients attributed to lactose consume at home are due to factors other than fast
      OCTT.

PMID- 23548007
TI  - Effect of probiotic species on irritable bowel syndrome symptoms: A bring up to
      date meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: immune system alteration in irritable bowel syndrome
      (IBS) patients may be modulated by probiotics. We assessed the efficacy of some
      probiotic species in alleviating characteristic IBS symptoms. MATERIAL AND
      METHODS: a meta-analysis of all identified randomized controlled trials comparing
      probiotics with placebo in treating IBS symptoms was performed with continuous
      data summarized using standardized mean differences (SMDs) with 95% confidence
      intervals (95% CIs), where appropriate. The random-effects model was employed in
      cases of heterogeneity; otherwise, fixed-effects models were used. RESULTS: meta
      analysis was performed with 10 of 24 studies identified as suitable for
      inclusion. Probiotics improved pain scores if they contained Bifidobacterium
      breve (SMD, - 0.34; 95% CI, - 0.66; -0.02), Bifidobacterium longum (SMD, -0.48;
      95% CI, - 0.91; -0.06), or Lactobacillus acidophilus (SMD, -0.31; 95% CI, -0.61; 
      0.01) species. Distension scores were improved by probiotics containing B. breve
      (SMD, -0.45; 95% CI, -0.77; -0.13), Bifidobacterium infantis, Lactobacillus
      casei, or Lactobacillus plantarum (SMD, -0.53; 95% CI, -1.00; -0.06) species. All
      probiotic species tested improved flatulence: B. breve (SMD, -0.42; 95% CI, 
      0.75;- 0.10), B. infantis, L. casei, L. plantarum (SMD, -0.60; 95% CI, -1.07; 
      0.13), B. longum, L. acidophilus, Lactobacillus bulgaricus, and Streptococcus
      salivarius ssp. thermophilus (SMD, -0.61; 95% CI, -1.01; -0.21). There was not a
      clear positive effect of probiotics concerning the quality of life. CONCLUSIONS:
      some probiotics are an effective therapeutic option for IBS patients, and the
      effects on each IBS symptom are likely species-specific. Future studies must
      focus on the role of probiotics in modulating intestinal microbiota and the
      immune system while considering individual patient symptom profiles.

PMID- 23548008
TI  - Joint position statement by "Sociedad Espanola de Patologia Digestiva" (Spanish
      Society of Gastroenterology) and "Sociedad Espanola de Farmacologia" (Spanish
      Society of Pharmacology) on biosimilar therapy for inflammatory bowel disease.
AB  - Biological drugs or biopharmaceutical products, manufactured with or from living
      organisms using biotechnology, have represented a therapeutic revolution for the
      control of inflammatory bowel disease (IBD). At present, in this indication and
      in our country, only two biological are approved, infliximab (IFX) and adalimumab
      (ADA), both of them monoclonal antibodies against tumor necrosis factor alpha.
      Effectiveness data are strong for both therapies, with maximum levels of
      scientific evidence.The upcoming expiry date for these biologicals' patents has
      allowed the potential marketing of so-called biosimilar agents for the IBD
      indication. While biosimilars are conceptually for biological what generics are
      for chemical drugs, the structural complexity of biosimilars and their biological
      and manufacturing variability lead to consider validation processes for these two
      types in humans as highly differential. Thus, in our setting, under the coverage
      of "Agencia Espanola del Medicamento y Productos Sanitarios (AEMPS)" (Spanish
      Agency of Medicines and Medical Devices), guidelines issued by the European
      Medicines Agency (EMA) are to be applied, which states that a number of stages or
      steps must be overcome in order to obtain approval for a biosimilar
      agent.However, despite the presence of these recommendations by EMA, which must
      be met by a biosimilar in order to be licensed in our marketplace, relevant
      uncertainties persist that only future decisions by EMA and AEMPS may clarify.
      The present stance by our task force is that biosimilar development should be
      undertaken according to established regulations, thus certifying their efficacy
      and safety. Similarly, this task force considers that results obtained from
      studies in rheumatoid arthritis (RA) should not be extrapolated to IBD since the
      biological variability of these complex structures will not ensure a lack of
      noticeable changes in efficacy and safety.

PMID- 23548009
TI  - Hepatic abscess caused by an ingested chicken bone.

PMID- 23548010
TI  - Loculated hydrothorax: an unusual complication of hepatic cirrhosis.

PMID- 23548011
TI  - Ischemic colitis due to vigorous physical exercise.
AB  - Physical exercise has been related with both beneficial effects on the
      gastrointestinal tract as with adverse effects on the latter. Gastrointestinal
      bleeding is one of these. In general, gastrointestinal bleeding is transient and
      mild. However, some cases caused by intestinal ischemia can sometimes be more
      serious due to the amount of bleeding and the presence of mucosal lesions. We
      present the case of a patient with abdominal pain and rectal bleeding caused by
      an extensive ischemic colitis due to vigorous physical exercise.

PMID- 23548012
TI  - [Liver encephalopaty].

PMID- 23548013
TI  - Clinical variability of mutations in the ABCB11 gene: a case report.

PMID- 23548014
TI  - Upper digestive tract hemorrhage in a child with heterotopic pancreas in a
      gastric diverticulum.

PMID- 23548015
TI  - Single intestinal metastasis of non-small cell lung carcinoma.

PMID- 23548016
TI  - Infectious esophagic fistula: A common virus with an extraordinary presentation.

PMID- 23548017
TI  - Tenofovir treatment of the severe acute hepatitis B.

PMID- 23548018
TI  - Ischemic colitis associated with hormonal contraceptive treatment delivered via
      vaginal ring.

PMID- 23548019
TI  - Artificial intelligence techniques in medicinal chemistry.

PMID- 23548020
TI  - The impact of computer science in molecular medicine: enabling high-throughput
      research.
AB  - The Human Genome Project and the explosion of high-throughput data have
      transformed the areas of molecular and personalized medicine, which are producing
      a wide range of studies and experimental results and providing new insights for
      developing medical applications. Research in many interdisciplinary fields is
      resulting in data repositories and computational tools that support a wide
      diversity of tasks: genome sequencing, genome-wide association studies, analysis
      of genotype-phenotype interactions, drug toxicity and side effects assessment,
      prediction of protein interactions and diseases, development of computational
      models, biomarker discovery, and many others. The authors of the present paper
      have developed several inventories covering tools, initiatives and studies in
      different computational fields related to molecular medicine: medical
      informatics, bioinformatics, clinical informatics and nanoinformatics. With these
      inventories, created by mining the scientific literature, we have carried out
      several reviews of these fields, providing researchers with a useful framework to
      locate, discover, search and integrate resources. In this paper we present an
      analysis of the state-of-the-art as it relates to computational resources for
      molecular medicine, based on results compiled in our inventories, as well as
      results extracted from a systematic review of the literature and other scientific
      media. The present review is based on the impact of their related publications
      and the available data and software resources for molecular medicine. It aims to
      provide information that can be useful to support ongoing research and work to
      improve diagnostics and therapeutics based on molecular-level insights.

PMID- 23548021
TI  - Ontologies in medicinal chemistry: current status and future challenges.
AB  - Recent years have seen a dramatic increase in the amount and availability of data
      in the diverse areas of medicinal chemistry, making it possible to achieve
      significant advances in fields such as the design, synthesis and biological
      evaluation of compounds. However, with this data explosion, the storage,
      management and analysis of available data to extract relevant information has
      become even a more complex task that offers challenging research issues to
      Artificial Intelligence (AI) scientists. Ontologies have emerged in AI as a key
      tool to formally represent and semantically organize aspects of the real world.
      Beyond glossaries or thesauri, ontologies facilitate communication between
      experts and allow the application of computational techniques to extract useful
      information from available data. In medicinal chemistry, multiple ontologies have
      been developed during the last years which contain knowledge about chemical
      compounds and processes of synthesis of pharmaceutical products. This article
      reviews the principal standards and ontologies in medicinal chemistry, analyzes
      their main applications and suggests future directions.

PMID- 23548022
TI  - New approaches in data integration for systems chemical biology.
AB  - Advances done in "-Omics" technologies in the last 20 years have made available
      to the researches huge amounts of data spanning a wide variety of biological
      processes from gene sequences to the metabolites present in a cell at a
      particular time. The management, analysis and representation of these data have
      been facilitated by mean of the advances made by biomedical informatics in areas
      such as data architecture and integration systems. However, despite the efforts
      done by biologists in this area, research in drug design adds a new level of
      information by incorporating data related with small molecules, which increases
      the complexity of these integration systems. Current knowledge in molecular
      biology has shown that it is possible to use comprehensive and integrative
      approaches to understand the biological processes from a systems perspective and
      that pathological processes can be mapped into biological networks. Therefore,
      current strategies for drug design are focusing on how to interact with or modify
      those networks to achieve the desired effects on what is called systems chemical
      biology. In this review several approaches for data integration in systems
      chemical biology will be analysed and described. Furthermore, because of the
      increasing relevance of the development and use of nanomaterials and their
      expected impact in the near future, the requirements of integration systems that
      incorporate these new data types associated with nanomaterials will also be
      analysed.

PMID- 23548023
TI  - From protein-protein interactions to rational drug design: are computational
      methods up to the challenge?
AB  - The study of protein-protein interactions (PPIs) has been growing for some years
      now, mainly as a result of easy access to high-throughput experimental data.
      Several computational approaches have been presented throughout the years as
      means to infer PPIs not only within the same species, but also between different
      species (e.g., host-pathogen interactions). The importance of unveiling the human
      protein interaction network is undeniable, particularly in the biological,
      biomedical and pharmacological research areas. Even though protein interaction
      networks evolve over time and can suffer spontaneous alterations, occasional
      shifts are often associated with disease conditions. These disorders may be
      caused by external pathogens, such as bacteria and viruses, or by intrinsic
      factors, such as auto-immune disorders and neurological impairment. Therefore,
      having the knowledge of how proteins interact with each other will provide a
      great opportunity to understand pathogenesis mechanisms, and subsequently support
      the development of drugs focused on very specific disease pathways and re
      targeting already commercialized drugs to new gene products. Computational
      methods for PPI prediction have been highlighted as an interesting option for
      interactome mapping. In this paper we review the techniques and strategies used
      for both experimental identification and computational inference of PPIs. We will
      then discuss how this knowledge can be used to create protein interaction
      networks (PINs) and the various methodologies applied to characterize and predict
      the so-called "disease genes" and "disease networks". This will be followed by an
      overview of the strategies employed to predict drug targets.

PMID- 23548024
TI  - MIANN models in medicinal, physical and organic chemistry.
AB  - Reducing costs in terms of time, animal sacrifice, and material resources with
      computational methods has become a promising goal in Medicinal, Biological,
      Physical and Organic Chemistry. There are many computational techniques that can
      be used in this sense. In any case, almost all these methods focus on few
      fundamental aspects including: type (1) methods to quantify the molecular
      structure, type (2) methods to link the structure with the biological activity,
      and others. In particular, MARCH-INSIDE (MI), acronym for Markov Chain Invariants
      for Networks Simulation and Design, is a well-known method for QSAR analysis
      useful in step (1). In addition, the bio-inspired Artificial-Intelligence (AI)
      algorithms called Artificial Neural Networks (ANNs) are among the most powerful
      type (2) methods. We can combine MI with ANNs in order to seek QSAR models, a
      strategy which is called herein MIANN (MI & ANN models). One of the first
      applications of the MIANN strategy was in the development of new QSAR models for
      drug discovery. MIANN strategy has been expanded to the QSAR study of proteins,
      protein-drug interactions, and protein-protein interaction networks. In this
      paper, we review for the first time many interesting aspects of the MIANN
      strategy including theoretical basis, implementation in web servers, and examples
      of applications in Medicinal and Biological chemistry. We also report new
      applications of the MIANN strategy in Medicinal chemistry and the first examples
      in Physical and Organic Chemistry, as well. In so doing, we developed new MIANN
      models for several self-assembly physicochemical properties of surfactants and
      large reaction networks in organic synthesis. In some of the new examples we also
      present experimental results which were not published up to date.

PMID- 23548025
TI  - Artificial neural networks for efficient clustering of conformational ensembles
      and their potential for medicinal chemistry.
AB  - The biological function of proteins is strictly related to their molecular
      flexibility and dynamics: enzymatic activity, protein-protein interactions,
      ligand binding and allosteric regulation are important mechanisms involving
      protein motions. Computational approaches, such as Molecular Dynamics (MD)
      simulations, are now routinely used to study the intrinsic dynamics of target
      proteins as well as to complement molecular docking approaches. These methods
      have also successfully supported the process of rational design and discovery of
      new drugs. Identification of functionally relevant conformations is a key step in
      these studies. This is generally done by cluster analysis of the ensemble of
      structures in the MD trajectory. Recently Artificial Neural Network (ANN)
      approaches, in particular methods based on Self-Organising Maps (SOMs), have been
      reported performing more accurately and providing more consistent results than
      traditional clustering algorithms in various data-mining problems. In the
      specific case of conformational analysis, SOMs have been successfully used to
      compare multiple ensembles of protein conformations demonstrating a potential in
      efficiently detecting the dynamic signatures central to biological function.
      Moreover, examples of the use of SOMs to address problems relevant to other
      stages of the drug-design process, including clustering of docking poses, have
      been reported. In this contribution we review recent applications of ANN
      algorithms in analysing conformational and structural ensembles and we discuss
      their potential in computer-based approaches for medicinal chemistry.

PMID- 23548026
TI  - Machine learning and social network analysis applied to Alzheimer's disease
      biomarkers.
AB  - Due to the fact that the number of deaths due Alzheimer is increasing, the
      scientists have a strong interest in early stage diagnostic of this disease.
      Alzheimer's patients show different kind of brain alterations, such as
      morphological, biochemical, functional, etc. Currently, using magnetic resonance
      imaging techniques is possible to obtain a huge amount of biomarkers; being
      difficult to appraise which of them can explain more properly how the pathology
      evolves instead of the normal ageing. Machine Learning methods facilitate an
      efficient analysis of complex data and can be used to discover which biomarkers
      are more informative. Moreover, automatic models can learn from historical data
      to suggest the diagnostic of new patients. Social Network Analysis (SNA) views
      social relationships in terms of network theory consisting of nodes and
      connections. The resulting graph-based structures are often very complex; there
      can be many kinds of connections between the nodes. SNA has emerged as a key
      technique in modern sociology. It has also gained a significant following in
      medicine, anthropology, biology, information science, etc., and has become a
      popular topic of speculation and study. This paper presents a review of machine
      learning and SNA techniques and then, a new approach to analyze the magnetic
      resonance imaging biomarkers with these techniques, obtaining relevant
      relationships that can explain the different phenotypes in dementia, in
      particular, different stages of Alzheimer's disease.

PMID- 23548027
TI  - Metabolism evolution based on network degrees of orthologous enzymes.
AB  - The evolution of orthologous proteins opens a new era of research where the
      concepts of orthology and paralogy have become more and more substantial, as the
      whole-genome comparison allows their identification in complete genomes.
      Functional specificity of proteins is understood to be conserved among orthologs
      but it shows much more variability among paralogs. We used this laying claim to
      identify inter-species interactions based on orthologous protein networks which
      are crucial for understanding the evolution of orthologous proteins. We analyzed
      six classes of enzymatic protein sequence data using the node degrees of
      orthologous proteins. The results demonstrated the evolutionary importance of the
      fatty acid syntheses and the photosynthetic system in algae. Methods which have
      successfully exploited network structure at many different levels of detail are a
      cornerstone of systems biology.

PMID- 23548028
TI  - Applied computational techniques on schizophrenia using genetic mutations.
AB  - Schizophrenia is a complex disease, with both genetic and environmental
      influence. Machine learning techniques can be used to associate different genetic
      variations at different genes with a (schizophrenic or non-schizophrenic)
      phenotype. Several machine learning techniques were applied to schizophrenia data
      to obtain the results presented in this study. Considering these data,
      Quantitative Genotype - Disease Relationships (QDGRs) can be used for disease
      prediction. One of the best machine learning-based models obtained after this
      exhaustive comparative study was implemented online; this model is an artificial
      neural network (ANN). Thus, the tool offers the possibility to introduce Single
      Nucleotide Polymorphism (SNP) sequences in order to classify a patient with
      schizophrenia. Besides this comparative study, a method for variable selection,
      based on ANNs and evolutionary computation (EC), is also presented. This method
      uses half the number of variables as the original ANN and the variables obtained
      are among those found in other publications. In the future, QDGR models based on
      nucleic acid information could be expanded to other diseases.

PMID- 23548029
TI  - Multi-classifier based on hard instances- new method for prediction of human
      immunodeficiency virus drug resistance.
AB  - There are several classification problems, which are difficult to solve using a
      single classifier because of the complexity of the decision boundary. Whereas a
      wide variety of multiple classifier systems have been built with the purpose of
      improving the recognition process, there is no universal method performing the
      best. This paper provides a review of different multi-classifiers and some
      application of them. Also it is shown a novel model of combining classifiers and
      its application to predicting human immunodeficiency virus drug resistance from
      genotype. The proposal is based on the use of different classifier models. It
      clusters the dataset considering the performance of the base classifiers. The
      system learns how to decide from the groups, by using a meta-classifier, which
      are the best classifiers for a given pattern. The proposed model is compared with
      well-known classifier ensembles and individual classifiers as well resulting the
      novel model in similar or even better performance.

PMID- 23548030
TI  - Estimation of the monthly average daily solar radiation using geographic
      information system and advanced case-based reasoning.
AB  - The photovoltaic (PV) system is considered an unlimited source of clean energy,
      whose amount of electricity generation changes according to the monthly average
      daily solar radiation (MADSR). It is revealed that the MADSR distribution in
      South Korea has very diverse patterns due to the country's climatic and
      geographical characteristics. This study aimed to develop a MADSR estimation
      model for the location without the measured MADSR data, using an advanced case
      based reasoning (CBR) model, which is a hybrid methodology combining CBR with
      artificial neural network, multiregression analysis, and genetic algorithm. The
      average prediction accuracy of the advanced CBR model was very high at 95.69%,
      and the standard deviation of the prediction accuracy was 3.67%, showing a
      significant improvement in prediction accuracy and consistency. A case study was
      conducted to verify the proposed model. The proposed model could be useful for
      owner or construction manager in charge of determining whether or not to
      introduce the PV system and where to install it. Also, it would benefit
      contractors in a competitive bidding process to accurately estimate the
      electricity generation of the PV system in advance and to conduct an economic and
      environmental feasibility study from the life cycle perspective.

PMID- 23548031
TI  - Prevalence and severity of behavioral and psychological symptoms of dementia
      (BPSD) in community dwelling Chinese: findings from the Shanghai three districts
      study.
AB  - OBJECTIVES: Studies of the prevalence and risk factors for behavioral and
      psychological symptoms of dementia (BPSD) have primarily been conducted in
      nursing home and clinic populations. Few population-based studies have been
      conducted in community-living persons with dementia. METHODS: In this cross
      sectional study, persons aged 65 and above who were living in the community were
      screened for dementia with the Chinese version of Mini-Mental State Examination
      (CMMSE) and Ability of Daily Living (ADL-14) scale. Participants with a diagnosis
      of dementia according to DSM-IV criteria made by trained neuropsychiatrists s
      were with the Neuropsychiatric Inventory assessed for BPSD by informant
      interview. RESULTS: Among 1271 persons with dementia, 50.1% had at least one
      BPSD. Sleep disturbance was the most common symptom (21.9%), followed by
      irritability (19.6%), and apathy (15.7%). About 40% (N = 501) of these problems
      were clinically significant (NPI score > 4). The NPI score was significantly
      associated with the CMMSE score, ADL score and education. CONCLUSION: BPSD are
      common among community living Chinese people with dementia, but the relatively
      lower prevalence rate and different pattern of symptoms from those reported in
      the USA, UK and Japan suggest the possible influence of cultural background and
      psychosocial environment.

PMID- 23548032
TI  - Between harm reduction, loss and wellness: on the occupational hazards of work.
AB  - Those working in the fields of harm reduction, healthcare, and human services
      must cope with a range of stresses, including post traumatic stress and vicarious
      trauma. Pain and loss are just a part of the job. So is dealing with premature
      death as a result of HIV, hypertension, and even overdose. Faced with a range of
      challenges, some workers in the field even turn to self-medication. For some, it
      is about pleasure; for others it is about alleviating suffering. In recent years,
      several leaders in the AIDS and harm reduction fields have died ahead of their
      time. Some stopped taking their medications; others overdosed. Rather than
      weakness or pathology, French sociologist Emile Durkheim saw self-destructive
      behavior as a byproduct of social disorganization and isolation, as a way of
      contending with a breakdown of social bonds and alienation. There are any number
      of reasons why such behavior becomes part of work for those involved with
      battling the dueling epidemics of Hepatitis C, HIV, and related concerns. Forms
      of stress related to this work include secondary trauma, compassion fatigue,
      organizational conflict, burnout, complications of direct services, and lack of
      funding. Faced with day-to- day struggles over poverty, punitive welfare systems,
      drug use, the war on drugs, high risk behavior, structural violence, and illness,
      many in the field are left to wonder how to strive for wellness when taking on so
      much pain. For some, self-injury and self-medication are ways of responding.
      Building on ethnographic methods, this reflective analysis considers the stories
      of those who have suffered, as well as a few of the ways those in the field cope
      with harm and pain. The work considers the moral questions we face when we see
      our friends and colleagues suffer. It asks how we as practitioners strive to
      create a culture of wellness and support in the fields of harm reduction,
      healthcare, and human services. Through a brief review of losses and literature
      thereof, the essay considers models of harm reduction practice that emphasize
      health, pleasure and sustainability for practitioners.

PMID- 23548033
TI  - Distance-mediated spatial neglect.
AB  - Unilateral spatial neglect (USN) is usually assessed by means of individual
      stimuli or single arrays of stimuli. Seldom are stimuli presented as multiple
      objects or in spatially separated blocks, except in some tests for object-based
      neglect. The distance between individual objects or blocks of stimuli in such
      stimuli is implicitly considered irrelevant. We report on the case of a patient,
      EC, who showed severe USN in his everyday behavior, yet performed normally on
      standard tests for USN. Presented with stimuli in separate blocks, he performed
      flawlessly with 4 cm gaps between blocks, yet ignored all leftward blocks of
      stimuli when the gap was larger than this. EC's dissociation between good
      performance on standard tasks and severe neglect with separate groups of stimuli,
      and the distance-mediated nature of his USN are novel observations with relevant
      theoretical and clinical implications. 

PMID- 23548034
TI  - Impact of non-dialysis chronic kidney disease on survival in patients with septic
      shock.
AB  - BACKGROUND: Chronic kidney disease (CKD) is known to expose the patient to a high
      risk of death due to cardiovascular and infective causes. In parallel, septic
      shock is a major challenge for cardiovascular and immune system. Therefore we
      tried to determine whether non-dialysis CKD, defined as a baseline estimated
      glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, for three months prior to
      the onset of septic shock is an independent risk factor for death. METHODS: All
      patients treated in a teaching hospital medical ICU for septic shock between
      January 2007 and December 2009 were retrospectively analyzed. Patients in whom
      baseline eGFR could not be determined (n=14) or patients treated by chronic
      dialysis (n=21) or kidney transplantation (n=14) were excluded. A total of 163
      patients were included. The population was divided according to baseline eGFR >=
      60 ml/min/1.73 m2 (non-CKD group, n=107) and < 60 ml/min/1.73 m2 (CKD group,
      n=56). Twenty-eight-day and 1-year survival curves were plotted. Prognostic
      factors were determined using Cox proportional hazards models. RESULTS: Baseline
      eGFR was significantly higher in the non-CKD group than in the CKD group (81 (67
      108) vs. 36 (28-44) ml/min/1.73 m2, respectively; p=0.001). Age, SAPS II, serum
      creatinine on admission and the number of patients with a history of diabetes,
      hypertension, heart failure, peripheral artery disease, coronary artery disease
      and statin medication were significantly higher in the CKD group than in the non
      CKD group. The mortality rate was lower in the non-CKD group than in the CKD
      group after 28 days (50% vs. 70%, respectively; p=0.03) and 1 year (64% vs. 82%,
      respectively; p=0.03). On multivariate analysis, the dichotomous variable CKD
      (eGFR < 60 ml/min/1.73 m2) remained significantly associated with the 28-day and
      1-year mortality. CONCLUSIONS: Non-dialysis CKD appears to be an independent risk
      factor for death after septic shock.

PMID- 23548035
TI  - Synthesis of 4-fluoromethylsydnones and their participation in alkyne
      cycloaddition reactions.
AB  - We report the synthesis and some structural studies of 4-trifluoromethyl, 4
      difluoromethyl-, and 4-monofluoromethylsydnones. All but the latter compounds are
      stable and represent effective precursors to a range of pyrazoles after
      cycloaddition reactions with alkynes. The cycloadditions are generally highly
      regioselective and provide 5-fluoromethylpyrazole products, although we have
      observed that Bn-substituted sydnones can provide an unexpected alkyne insertion
      mode that generates the 3-fluoromethyl isomer.

PMID- 23548036
TI  - Hazard Evaluation Support System (HESS) for predicting repeated dose toxicity
      using toxicological categories.
AB  - Repeated dose toxicity (RDT) is one of the most important hazard endpoints in the
      risk assessment of chemicals. However, due to the complexity of the endpoints
      associated with whole body assessment, it is difficult to build up a
      mechanistically transparent structure-activity model. The category approach,
      based on mechanism information, is considered to be an effective approach for
      data gap filling for RDT by read-across. Therefore, a library of toxicological
      categories was developed using experimental RDT data for 500 chemicals and
      mechanistic knowledge of the effects of these chemicals on different organs. As a
      result, 33 categories were defined for 14 types of toxicity, such as
      hepatotoxicity, hemolytic anemia, etc. This category library was then
      incorporated in the Hazard Evaluation Support System (HESS) integrated
      computational platform to provide mechanistically reasonable predictions of RDT
      values for untested chemicals. This article describes the establishment of a
      category library and the associated HESS functions used to facilitate the
      mechanistically reasonable grouping of chemicals and their subsequent read
      across.

PMID- 23548037
TI  - Porous Co3O4 nanorods-reduced graphene oxide with intrinsic peroxidase-like
      activity and catalysis in the degradation of methylene blue.
AB  - A facile two step process was developed for the synthesis of porous Co3O4
      nanorods-reduced graphene oxide (PCNG) hybrid materials based on the hydrothermal
      treatment cobalt acetate tetrahydrate and graphene oxide in a glycerol-water
      mixed solvent, followed by annealing the intermediate of reduced graphene oxide
      supported Co(CO3)0.5(OH).0.11H2O nanorods in a N2 atmosphere. The morphology and
      microstructure of the composites were examined by X-ray diffraction, X-ray
      photoelectron spectroscopy, transmission electron microscopy and Raman
      spectroscopy. It is shown that the obtained PCNG have intrinsic peroxidase-like
      activity. The PCNG are utilized for the catalytic degradation of methylene blue.
      The good catalytic performance of the composites could be attributed to the
      synergy between the functions of porous Co3O4 nanorods and reduced graphene
      oxide.

PMID- 23548038
TI  - Cathodoluminescence and Raman spectroscopic analyses of Nd- or Yb-doped Y2O3
      transparent ceramics.
AB  - In this article, we discuss a study of the influence of Nd(3+) and Yb(3+) dopants
      on the spectroscopic behavior of Y2O3 ceramic polycrystals, by using Raman and
      cathodoluminescence (CL) spectroscopy. Doping with Yb at 1 at % results in a blue
      shift of the Raman band but has no pronounced influence on the intrinsic emission
      of Y2O3, while doping with Nd shows a red shift of the Raman band and markedly
      enhances the oxygen vacancy related 380 nm CL band. Lattice distortion induced by
      the alien ion incorporation and variations of effective absorption coefficients
      by adding different dopants were assessed using Raman spectroscopy. Moreover,
      both CL and Raman spectroscopies were applied to examine the homogeneity and
      distribution of the dopants throughout the ceramic microstructure. Visualization
      of sample homogeneity was made available by hyperspectral imaging of the local
      intensity of CL bands, while spectral deconvolution was performed to retrieve
      local structural variations at grain boundaries. We also confirmed that the
      combination of Raman and CL spectroscopies leads to a reliable and useful
      methodology for the examination of dopants in yttria ceramic materials.

PMID- 23548039
TI  - Benign proliferative breast diseases among female patients at a sub-Saharan
      Africa tertiary hospital: a cross sectional study.
AB  - BACKGROUND: Non-cancerous diseases of the breast have assumed increasing
      importance because of the public awareness of breast cancer. These benign
      diseases are a recognized important risk factor for later breast cancer which can
      develop in either breast. The risk estimate of these benign breast diseases has
      not been well established in sub Saharan Africa. Women with benign proliferative
      or atypical breast lesions have a two- fold risk of developing breast cancer in
      western populations. The purpose of this study therefore was to determine the
      prevalence of proliferative disease ( BPBD) with and without atypia among Ugandan
      Black women. METHODS: A cross-sectional descriptive study conducted at Mulago
      Hospital Breast Clinic between January 2012 and June 2012; 208 women aged 12
      years and above with palpable breast lumps were screened. Fine needle aspiration
      biopsies were taken for cytological examination. RESULTS: Of the 208 women with
      benign breast lumps screened, 195 were recruited in the study. The prevalence of
      BPBD was 18% (35/195). BPBD with atypia was 5.6% (11/195). The mean age and body
      mass index (BMI) were 28.4 years and 23.26 kg/m2 respectively. The commonest
      lesions were fibroadenomas for 57%, (111/195), and fibrocystic change were 21%
      (40/195). Most BPBD with atypia lesions were in the fibrocystic category.
      CONCLUSIONS: Benign proliferative breast diseases are common, found mostly among
      premenopausal women. A significant proportion of BPBD had atypical proliferation.
      An accurate breast cancer risk estimate study for BPBD is recommended.

PMID- 23548040
TI  - Probabilistic strain optimization under constraint uncertainty.
AB  - BACKGROUND: An important step in strain optimization is to identify reactions
      whose activities should be modified to achieve the desired cellular objective.
      Preferably, these reactions are identified systematically, as the number of
      possible combinations of reaction modifications could be very large. Over the
      last several years, a number of computational methods have been described for
      identifying combinations of reaction modifications. However, none of these
      methods explicitly address uncertainties in implementing the reaction activity
      modifications. In this work, we model the uncertainties as probability
      distributions in the flux carrying capacities of reactions. Based on this model,
      we develop an optimization method that identifies reactions for flux capacity
      modifications to predict outcomes with high statistical likelihood. RESULTS: We
      compare three optimization methods that select an intervention set comprising up-
      or down-regulation of reaction flux capacity: CCOpt (Chance constrained
      optimization), DetOpt (Deterministic optimization), and MCOpt (Monte Carlo-based
      optimization). We evaluate the methods using a Monte Carlo simulation-based
      method, MCEval (Monte Carlo Evaluations). We present two case studies analyzing a
      CHO cell and an adipocyte model. The flux capacity distributions required for our
      methods were estimated from maximal reaction velocities or elementary mode
      analysis. The intervention set selected by CCOpt consistently outperforms the
      intervention set selected by DetOpt in terms of tolerance to flux capacity
      variations. MCEval shows that the optimal flux predicted based on the CCOpt
      intervention set is more likely to be obtained, in a probabilistic sense, than
      the flux predicted by DetOpt. The intervention sets identified by CCOpt and MCOpt
      were similar; however, the exhaustive sampling required by MCOpt incurred
      significantly greater computational cost. CONCLUSIONS: Maximizing tolerance to
      variable engineering outcomes (in modifying enzyme activities) can identify
      intervention sets that statistically improve the desired cellular objective.

PMID- 23548041
TI  - Photoluminescent gold-copper nanoparticle alloys with composition-tunable near
      infrared emission.
AB  - Discrete gold nanoparticles with diameters between 2 and 3 nm show remarkable
      properties including enhanced catalytic behavior and photoluminescence. However,
      tunability of these properties is limited by the tight size range within which
      they are observed. Here, we report the synthesis of discrete, bimetallic gold
      copper nanoparticle alloys (diameter ? 2-3 nm) which display photoluminescent
      properties that can be tuned by changing the alloy composition. Electron
      microscopy, X-ray photoelectron spectroscopy, inductively coupled plasma mass
      spectrometry, and pulsed-field gradient stimulated echo (1)H NMR measurements
      show that the nanoparticles are homogeneous, discrete, and crystalline. Upon
      varying the composition of the nanoparticles from 0% to 100% molar ratio copper,
      the photoluminescence maxima shift from 947 to 1067 nm, with excitation at 360
      nm. The resulting particles exhibit brightness values (molar extinction
      coefficient (epsilon) * quantum yield (Phi)) that are more than an order of
      magnitude larger than the brightest near-infrared-emitting lanthanide complexes
      and small-molecule probes evaluated under similar conditions.

PMID- 23548042
TI  - Reduction in thyroid perfusion after bevacizumab treatment.

PMID- 23548043
TI  - Quantitative shape analysis with weighted covariance estimates for increased
      statistical efficiency.
AB  - BACKGROUND: The introduction and statistical formalisation of landmark-based
      methods for analysing biological shape has made a major impact on comparative
      morphometric analyses. However, a satisfactory solution for including information
      from 2D/3D shapes represented by 'semi-landmarks' alongside well-defined
      landmarks into the analyses is still missing. Also, there has not been an
      integration of a statistical treatment of measurement error in the current
      approaches. RESULTS: We propose a procedure based upon the description of
      landmarks with measurement covariance, which extends statistical linear modelling
      processes to semi-landmarks for further analysis. Our formulation is based upon a
      self consistent approach to the construction of likelihood-based parameter
      estimation and includes corrections for parameter bias, induced by the degrees of
      freedom within the linear model. The method has been implemented and tested on
      measurements from 2D fly wing, 2D mouse mandible and 3D mouse skull data. We use
      these data to explore possible advantages and disadvantages over the use of
      standard Procrustes/PCA analysis via a combination of Monte-Carlo studies and
      quantitative statistical tests. In the process we show how appropriate weighting
      provides not only greater stability but also more efficient use of the available
      landmark data. The set of new landmarks generated in our procedure ('ghost
      points') can then be used in any further downstream statistical analysis.
      CONCLUSIONS: Our approach provides a consistent way of including different forms
      of landmarks into an analysis and reduces instabilities due to poorly defined
      points. Our results suggest that the method has the potential to be utilised for
      the analysis of 2D/3D data, and in particular, for the inclusion of information
      from surfaces represented by multiple landmark points.

PMID- 23548044
TI  - CSAR benchmark exercise 2011-2012: evaluation of results from docking and
      relative ranking of blinded congeneric series.
AB  - The Community Structure-Activity Resource (CSAR) recently held its first blinded
      exercise based on data provided by Abbott, Vertex, and colleagues at the
      University of Michigan, Ann Arbor. A total of 20 research groups submitted
      results for the benchmark exercise where the goal was to compare different
      improvements for pose prediction, enrichment, and relative ranking of congeneric
      series of compounds. The exercise was built around blinded high-quality
      experimental data from four protein targets: LpxC, Urokinase, Chk1, and Erk2.
      Pose prediction proved to be the most straightforward task, and most methods were
      able to successfully reproduce binding poses when the crystal structure employed
      was co-crystallized with a ligand from the same chemical series. Multiple
      evaluation metrics were examined, and we found that RMSD and native contact
      metrics together provide a robust evaluation of the predicted poses. It was
      notable that most scoring functions underpredicted contacts between the hetero
      atoms (i.e., N, O, S, etc.) of the protein and ligand. Relative ranking was found
      to be the most difficult area for the methods, but many of the scoring functions
      were able to properly identify Urokinase actives from the inactives in the
      series. Lastly, we found that minimizing the protein and correcting histidine
      tautomeric states positively trended with low RMSD for pose prediction but
      minimizing the ligand negatively trended. Pregenerated ligand conformations
      performed better than those that were generated on the fly. Optimizing docking
      parameters and pretraining with the native ligand had a positive effect on the
      docking performance as did using restraints, substructure fitting, and shape
      fitting. Lastly, for both sampling and ranking scoring functions, the use of the
      empirical scoring function appeared to trend positively with the RMSD. Here, by
      combining the results of many methods, we hope to provide a statistically
      relevant evaluation and elucidate specific shortcomings of docking methodology
      for the community. 

PMID- 23548045
TI  - A quantitative homogeneous assay for fragile X mental retardation 1 protein.
AB  - BACKGROUND: Hypermethylation of the fragile X mental retardation 1 gene FMR1
      results in decreased expression of FMR1 protein FMRP, which is the underlying
      cause of Fragile X syndrome - an incurable neurological disorder characterized by
      mental retardation, anxiety, epileptic episodes and autism. Disease-modifying
      therapies for Fragile X syndrome are thus aimed at treatments that increase the
      FMRP expression levels in the brain. We describe the development and
      characterization of two assays for simple and quantitative detection of FMRP
      protein. METHOD: Antibodies coupled to fluorophores that can be employed for time
      resolved Forster's resonance energy transfer were used for the development of
      homogeneous, one-step immunodetection. Purified recombinant human FMRP and
      patient cells were used as control samples for assay development. RESULTS: The
      assays require small sample amounts, display high stability and reproducibility
      and can be used to quantify endogenous FMRP in human fibroblasts and peripheral
      blood mononuclear cells. Application of the assays to FXS patient cells showed
      that the methods can be used both for the characterization of clinical FXS
      patient samples as well as primary readouts in drug-discovery screens aimed at
      increasing endogenous FMRP levels in human cells. CONCLUSION: This study provides
      novel quantitative detection methods for FMRP in FXS patient cells. Importantly,
      due to the simplicity of the assay protocol, the method is suited to be used in
      screening applications to identify compounds or genetic interventions that result
      in increased FMRP levels in human cells.

PMID- 23548046
TI  - Recent progress in the use of genetics to understand links between type 2
      diabetes and related metabolic traits.
AB  - Genome-wide association studies have identified genetic variants associated with
      increased risk of type 2 diabetes. The aim of this review is to highlight some of
      the insights into the mechanism underlying type 2 diabetes provided by genetic
      association studies. 

PMID- 23548048
TI  - Association of socio-demographic factors and parental education with depressive
      symptoms among older African Americans and Caribbean Blacks.
AB  - OBJECTIVE: The purpose of this study was to examine ethnic variation in the
      relationship between individual socio-demographic factors, parental educational
      level, and late-life depressive symptoms in older African Americans and Caribbean
      Blacks. METHOD: This cross-sectional study used data from the National Survey of
      American Life. A subsample of older African Americans (N = 837) and Caribbean
      Blacks (N = 271) was analyzed using multiple regression analysis. RESULTS:
      Findings suggest differences in predictors of depressive symptoms for the two
      ethnic groups. Among older African Americans, lower educational attainment and
      lower income were predictive risk factors for higher depressive symptoms.
      Findings among older Caribbean Blacks suggest that nativity and income were
      significantly associated with depressive symptoms. This study did not find
      support for any association between parental education and late-life depressive
      symptoms. CONCLUSION: This study adds new information by considering ethnic
      variation in an examination of depressive symptoms in older Black Americans. The
      results contribute to the growing awareness of the older Caribbean Black
      population in the United States.

PMID- 23548047
TI  - Anti-tumor necrosis factor VNAR single domains reduce lethality and regulate
      underlying inflammatory response in a murine model of endotoxic shock.
AB  - BACKGROUND: In sepsis, tumor necrosis factor (TNF) is the key factor triggering
      respiratory burst, tissue injury and disseminated coagulation. Anti-TNF
      strategies based on monoclonal antibodies or F(ab')2 fragments have been used in
      sepsis with contradictory results. Immunoglobulin new antigen receptors (IgNAR)
      are a unique subset of antibodies consisting of five constant (CNAR) and one
      variable domains (VNAR). VNAR domains are the smallest, naturally occurring,
      antibody-based immune recognition units, having potential use as therapy. Our aim
      was to explore the impact of an anti-TNF VNAR on survival in an experimental
      model of endotoxic shock. Also, mRNA expression and serum protein of several
      inflammatory molecules were measured. RESULTS: Endotoxic shock was induced by
      lipopolysaccharide (LPS) in male Balb/c mice. Animals were treated with anti-TNF
      VNAR domains, F(ab')2 antibody fragments, or saline solution 15 minutes before, 2
      h and 24 h after lethal dose100 (LD100) LPS administration. TNF blockade with
      either VNAR domains or F(ab')2 fragments were associated with lower mortality
      (60% and 75%, respectively) compared to LD100. Challenge with LPS induced
      significant production of serum TNF and interleukins -10 and -6 at 3 h. After
      that, significant reduction of IL-6 at 24 h (vs 3 h) was shown only in the VNAR
      group. Nitrites level also increased in response to LPS. In liver, TNF and IL-10
      mRNA expression showed a pro-inflammatory imbalance in response to LPS. Blocking
      TNF was associated with a shift towards an anti-inflammatory status; however,
      polarization was more pronounced in animals receiving F(ab')2 fragments than in
      those with VNAR therapy. With regard to IL-6, gene expression was increased at 3
      h in all groups. TNF blockade was associated with rapid and sustained suppression
      of IL-6 expression, even more evident in the VNAR group. Finally, expression of
      inducible-nitric oxide synthase (iNOS) increased in response to LPS at 3 h, but
      this was decreased at 24 h only in the anti-TNF VNAR group. CONCLUSIONS: Anti-TNF
      VNAR single domains improved survival in a murine model of endotoxic shock.
      Protection was associated with regulation in the TNF/IL-10 balance, attenuation
      of IL-6 and iNOS gene expression in the liver as well as decreased serum IL-6
      concentration.

PMID- 23548049
TI  - Predicting copper toxicity to different earthworm species using a multicomponent
      Freundlich model.
AB  - This study aimed to develop bioavailability models for predicting Cu toxicity to
      earthworms (Lumbricus rubellus, Aporrectodea longa, and Eisenia fetida) in a
      range of soils of varying properties. A multicomponent Freundlich model,
      complying with the basic assumption of the biotic ligands model, was used to
      relate Cu toxicity to the free Cu(2+) activity and possible protective cations in
      soil porewater. Median lethal concentrations (LC50s) of Cu based on the total Cu
      concentration varied in each species from soil to soil, reaching differences of
      approximately a factor 9 in L. rubellus, 49 in A. longa and 45 in E. fetida. The
      relative sensitivity of the earthworms to Cu in different soils followed the same
      order: L. rubellus > A. longa > E. fetida. Only pH not other cations (K(+),
      Ca(2+), Na(+), and Mg(2+)) were found to exert significant protective effects
      against Cu toxicity to earthworms. The Freundlich-type model in which the
      protective effects of pH were included, explained 84%, 94%, and 96% of variations
      in LC50s of Cu (expressed as free ion activity) for L. rubellus, A. longa, and E.
      fetida, respectively. Predicted LC50s never differed by a factor of more than 2
      from the observed LC50s. External validation of the model showed a similar level
      of precision, even though toxicity data for other soil organisms and for
      different endpoints were used. The findings of the present study showed the
      possibility of extrapolating the developed toxicity models for one earthworm
      species to another species. Moreover, the Freundlich-type model in which the free
      Cu(2+) activity and pH in soil porewater are considered can even be used to
      predict toxicity for other soil invertebrates and plants.

PMID- 23548050
TI  - Blurring personal health and public priorities: an analysis of celebrity health
      narratives in the public sphere.
AB  - This article explores the functions of personal celebrity health narratives in
      the public sphere. This study examines data about 157 celebrities, including
      athletes, actors, musicians, and politicians, who have shared private information
      regarding a personal health situation (or that of a loved one) with others in the
      public domain. Part of a larger project on celebrity health narratives, this
      article highlights three key functions that celebrity health narratives perform-
      education, inspiration, and activism--and discusses the implications for
      celebrities and for public conversations about health-related issues.

PMID- 23548051
TI  - Validity of the "Drift without pronation" sign in conversion disorder.
AB  - BACKGROUND: Conversion disorder (CD) is a psychiatric disorder, yet the diagnosis
      cannot be established without the expertise of a neurologist, as distinguishing a
      functional from an organic symptom relies on careful bedside examination. Joseph
      Babinski considered the absence of pronator drift as a 'positive sign' for
      hysterical paresis but the validity of this sign has never been evaluated. The
      aim of this study was to examine the sensitivity and specificity of the "drift
      without pronation" sign. METHODS: Twenty-six patients with unilateral functional
      upper limb paresis diagnosed with CD (DSM-IV) and a control group of 28 patients
      with an organic neurological condition were consecutively included. The arm
      stabilisation test was performed with arms stretched out in full supination,
      fingers adducted, eyes closed for 10 seconds. A positive "drift without
      pronation" sign was defined by the presence of a downward drift without
      pronation. RESULTS: All CD subjects (100%) displayed a positive sign when only
      7.1% of organic subjects did (Fisher's p < 0.001). The sign yielded a sensitivity
      of 100% (95% CI:84%-100%) and a specificity of 93% (95% CI:76%-98%). CONCLUSION:
      The observation of a "drift without pronation" sign is specific for Conversion
      Disorder and can be of help in making a quick distinction between organic and
      functional paresis at the bedside.

PMID- 23548053
TI  - Curcumin/Gd loaded apoferritin: a novel "theranostic" agent to prevent
      hepatocellular damage in toxic induced acute hepatitis.
AB  - Apoferritin has been exploited to deliver simultaneously therapeutic and imaging
      agents (loaded into its internal cavity) to hepatocytes as this protein is
      efficiently taken up from blood by hepatocyte scavenger receptor class A type 5
      via the ferritin transporting route. To this purpose the protein has been loaded
      with the magnetic resonance imaging (MRI) contrast agent GdHPDO3A and curcumin, a
      polyphenolic substance endowed with multiple pharmacological actions, namely:
      antioxidant, anti-inflammatory, antineoplastic. Curcumin and GdHPDO3A loaded
      apoferritin has been used with the aim to attenuate the thioacetamide-induced
      hepatitis together with the evaluation by MRI of drug delivery efficiency. Mice
      pretreated by intraperitoneal administration showed significantly attenuated
      hepatic injury as assessed by measuring alanine aminotransferase (ALT) activity
      in plasma and by histology assessment. The encapsulation of curcumin inside the
      apoferritin cavity significantly increases its stability and bioavailability
      while maintaining its therapeutic anti-inflammatory properties.

PMID- 23548052
TI  - A pilot study of yoga as self-care for arthritis in minority communities.
AB  - BACKGROUND: While arthritis is the most common cause of disability, non-Hispanic
      blacks and Hispanics experience worse arthritis impact despite having the same or
      lower prevalence of arthritis compared to non-Hispanic whites. People with
      arthritis who exercise regularly have less pain, more energy, and improved sleep,
      yet arthritis is one of the most common reasons for limiting physical activity.
      Mind-body interventions, such as yoga, that teach stress management along with
      physical activity may be well suited for investigation in both osteoarthritis and
      rheumatoid arthritis. Yoga users are predominantly white, female, and college
      educated. There are few studies that examine yoga in minority populations; none
      address arthritis. This paper presents a study protocol examining the feasibility
      and acceptability of providing yoga to an urban, minority population with
      arthritis. METHODS/DESIGN: In this ongoing pilot study, a convenience sample of
      20 minority adults diagnosed with either osteoarthritis or rheumatoid arthritis
      undergo an 8-week program of yoga classes. It is believed that by attending yoga
      classes designed for patients with arthritis, with racially concordant
      instructors; acceptability of yoga as an adjunct to standard arthritis treatment
      and self-care will be enhanced. Self-care is defined as adopting behaviors that
      improve physical and mental well-being. This concept is quantified through
      collecting patient-reported outcome measures related to spiritual growth, health
      responsibility, interpersonal relations, and stress management. Additional
      measures collected during this study include: physical function,
      anxiety/depression, fatigue, sleep disturbance, social roles, and pain; as well
      as baseline demographic and clinical data. Field notes, quantitative and
      qualitative data regarding feasibility and acceptability are also collected.
      Acceptability is determined by response/retention rates, positive qualitative
      data, and continuing yoga practice after three months. DISCUSSION: There are a
      number of challenges in recruiting and retaining participants from a community
      clinic serving minority populations. Adopting behaviors that improve well-being
      and quality of life include those that integrate mental health (mind) and
      physical health (body). Few studies have examined offering integrative modalities
      to this population. This pilot was undertaken to quantify measures of feasibility
      and acceptability that will be useful when evaluating future plans for expanding
      the study of yoga in urban, minority populations with arthritis. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01617421.

PMID- 23548054
TI  - Loss of person-specific knowledge in Alzheimer's disease: evidence from priming.
AB  - Semantic deficits in Alzheimer's disease (AD) are often more severe for items
      that are characterized by a unique semantic and lexical association, such as
      famous people. Whether these deficits are due to the degradation of semantic
      information or a deficit in the ability to intentionally access semantic
      knowledge remains controversial. To assess the integrity of the semantic system
      without explicitly accessing it, a priming paradigm was used. Semantic and
      repetition priming effects in individuals with AD (n = 7) and age-matched
      controls (n = 13) were measured in a familiarity judgment task using visually
      presented names of famous people. A defective priming effect in AD subjects was
      observed in the semantic priming but not in the repetition priming condition.
      Therefore, the semantic impairments observed in AD may indicate a degraded
      representation of the semantic information concerning famous people. 

PMID- 23548055
TI  - A coupling of benzamides and donor/acceptor diazo compounds to form gamma-lactams
      via Rh(III)-catalyzed C-H activation.
AB  - The coupling of O-pivaloyl benzhydroxamic acids with donor/acceptor diazo
      compounds provides isoindolones in high yield. The reaction tolerates a broad
      range of benzhydroxamic acids and diazo compounds, including substituted 2,2,2
      trifluorodiazoethanes. Mechanistic experiments suggested that C-H activation is
      turnover-limiting and irreversible and that insertion of the diazo compound
      favors electron-deficient substrates.

PMID- 23548056
TI  - Synthetic route to chiral indolines via ring-opening/C-N cyclization of activated
      2-haloarylaziridines.
AB  - A practical approach for the synthesis of 3-substituted indolines via regio- and
      stereoselective SN2-type ring-opening of 2-(2-halophenyl)-N-tosylaziridines with
      heteroatomic nucleophiles (O, N, and S) followed by palladium-catalyzed
      intramolecular C-N cyclization is reported in excellent yields (up to >99%) and
      enantiomeric excess (ee 99%).

PMID- 23548057
TI  - Engaging First Nation and Inuit communities in asthma management and control:
      assessing cultural appropriateness of educational resources.
AB  - INTRODUCTION: Asthma is a growing concern in First Nations and Inuit communities.
      As with many health indicators and outcomes, Aboriginal peoples living in remote
      areas experience greater disparities in respiratory health compared with non
      Aboriginal Canadians. Therefore, it is critically important to take into account
      their unique needs when developing asthma educational materials and resources.
      The purpose of this study is to assess the cultural relevance of existing asthma
      education materials for First Nations and Inuit peoples. Five First Nations and
      Inuit communities from across Canada participated in the project. METHODS: A
      combination of quantitative evaluations (eg surveys) and qualitative approaches
      (eg open discussion, live chats) were used to assess printed and web-based asthma
      education materials. Participants represented First Nations and Inuit communities
      from across Canada and were selected on the basis of age and role: 6 to 12 years
      old (children), 12 and over (youth), parents and grandparents, community leaders
      and teachers, and community advisory group members. RESULTS: In general, the
      results showed that although participants of all age categories liked the
      selection of asthma educational materials and resources, they identified pictures
      and images related to First Nations and Inuit people living and coping with
      asthma as ways of improving cultural relevance. This reinforces findings that
      tailoring materials to include Aboriginal languages, ceremonies and traditions
      would enhance their uptake. Our findings also demonstrate that visually based
      content in both printed and virtual form were the preferred style of learning of
      all participants, except young children who preferred to learn through play and
      interactive activities. CONCLUSIONS: Asthma is a growing concern in First Nations
      and Inuit communities. Given this concern, it is essential to understand cultural
      needs and preferences when developing asthma education materials and resources.
      The findings from this research emphasize the need to adapt existing asthma
      educational materials to better suit First Nations and Inuit cultures and the
      importance of directly engaging community members in the process.

PMID- 23548058
TI  - Genomic analysis of a newly isolated of Japanese encephalitis virus strain, CQ11
      66, from a pediatric patient in China.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) is one of the major causative
      agents of viral encephalitis in East Asia, Southeast Asia and Australia. However,
      no clinical JEV strain has yet been isolated from JE patients in Chongqing,
      China. In this study, we report the genomic analysis of a new JEV strain, CQ11
      66, isolated from a pediatric patient in Chongqing, China. FINDINGS: Virus
      isolation was carried out in BHK-21 cells. Nested PCR was used to detect and
      isolate the JEV strain, and computer analysis of phylogenetic relationships,
      nucleic acid homology studies and deduction of the amino acid sequence were
      conducted using ClustalX (1.8) and Mega5 software. The JEV strain CQ11-66 was
      isolated from patient cerebrospinal fluid. The sequenced genome of CQ11-66 was
      10,863 nucleotides in length, whereas other strains, such as SX09S-01, contain
      10,965 nucleotides. Sequence comparison of the CQ11-66 polyprotein open reading
      frame (ORF) with those of 21 other JEV strains revealed that the nucleotide
      sequence divergence ranged from 1.68% to 18.46%. Sequence analysis of the full
      length CQ11-66 E gene sequence with those of 30 other JEV isolates also
      identified nucleotide divergence, ranging from 1.69% to 18.74%. Phylogenetic
      analyses indicated that the CQ11-66 strain belonged to genotype III. CONCLUSIONS:
      JEV genotype III still circulates in Chongqing and it is therefore important for
      active surveillance of JEV genotype III to be conducted in the pediatric
      population.

PMID- 23548059
TI  - High rate performance of flexible pseudocapacitors fabricated using ionic-liquid
      based proton conducting polymer electrolyte with poly(3, 4
      ethylenedioxythiophene):poly(styrene sulfonate) and its hydrous ruthenium oxide
      composite electrodes.
AB  - We report the studies on all-solid-state flexible pseudocapacitors based on poly
      (3,4-ethylenedioxythiophene)-poly (styrene sulfonate) (PEDOT-PSS) and PEDOT
      PSS/hydrous ruthenium oxide composite electrodes separated by nonaqueous proton
      conducting polymer electrolyte. Structural, thermal and electrochemical
      properties including high ionic conductivity (6.2 * 10(-2) S cm(-1) at 20 
      degrees C) of the polymer electrolyte, comprising ionic liquid 1-ethyl 3-methyl
      imidazolium hydrogen sulfate (EMIHSO4) immobilized in the blend of poly (vinyl
      alcohol) (PVA) and poly (vinyl pyrrolidone) (PVP), demonstrate its excellent
      suitability in supercapacitor fabrication. A substantial improvement in the
      specific capacitance (hence the specific energy) has been obtained when the PEDOT
      PSS electrodes in the symmetrical pseudocapacitor are replaced by the composite
      electrodes PEDOT-PSS/RuO2.xH2O. High rate capability of the capacitor cell (with
      PEDOT-PSS electrodes) has been observed, as evidenced from the high knee
      frequency (~966 Hz), low response time (~70 ms) and high pulse power (~10.2 kW
      kg(-1)), observed by impedance analysis. Almost rectangular (capacitive) cyclic
      voltammetric patterns for high scan rates (up to 15 V s(-1)) confirm the high
      rate performance of the pseudocapacitor. The PEDOT-PSS/RuO2.xH2O composite
      electrodes show the lower rate capability (knee frequency ~312 Hz, response time
      ~1 s, pulse power ~3.2 kW kg(-1) and capacitive CV response up to 500 mV s(-1))
      because of slow exchange of charges at the interfaces via RuO2.xH2O. However, the
      pseudocapacitor with composite electrodes shows higher rate performance relative
      to many reported RuO2.xH2O systems. About 15% improvement is noticed in the
      capacitance value when the capacitor with composite electrodes is initially
      charged and discharged up to ~200 cycles. Thereafter, the cell shows almost
      constant value of specific capacitance (~70 F g(-1)) for 1000 cycles.

PMID- 23548060
TI  - Wearing ambidextrous vinyl gloves does not impair manual dexterity.
AB  - Universal precautions mandate that health care workers wear gloves to prevent the
      unintended spread of bloodborne pathogens. Gloves may affect manual dexterity,
      generally delaying task completion. Our previous study showed that wearing the
      wrong size latex surgical glove degraded manual dexterity. The use of non-sterile
      and non-latex gloves may limit certain risks and be more cost-effective. However,
      such gloves may produce different results. We hypothesized that ambidextrous
      vinyl examination gloves would degrade manual dexterity compared with bare hands.
      We studied 20 random subjects from a medical environment. Subjects performed a
      standard battery of Grooved Pegboard tasks while bare-handed, wearing
      ambidextrous non-sterile vinyl gloves that were their preferred size, a size too
      small, and a size too large. The order was randomized with a Latin Square design
      to minimize the effects of time, boredom, and fatigue on the subjects. Subjects
      were also invited to comment on the fit of different size gloves. Wearing vinyl
      gloves of both the preferred size and a size up or down failed to affect manual
      dexterity vs. bare hands on time to insert pegs, and pegs dropped during
      insertion or removal. In contrast, the time to remove pegs was reduced by wearing
      preferred size vinyl gloves compared with performing the task with bare hands
      (P<0.05). Subjects reported a generally poor fit in all sizes. Vinyl gloves that
      were too small caused significant hand discomfort. Vinyl gloves surprisingly do
      not degrade manual dexterity even when worn in ill-fitting sizes. Wearing a
      preferred size vinyl glove vs. bare hands may improve dexterity in selected
      tasks. Choosing a comfortable, large size seems the best strategy when the
      preferred size is unavailable. Thinner vinyl gloves may improve grip and may not
      degrade touch as much as latex surgical gloves and may thus represent a
      reasonable choice for selected tasks.

PMID- 23548061
TI  - Multi-analyte approach for determining the extraction of tobacco constituents
      from pouched snus by consumers during use.
AB  - BACKGROUND: Snus is a smokeless oral tobacco product with a significant history
      of use in Sweden, where it is regulated under food legislation. Users place a
      small porous sachet or a pinch of loose snus between the upper jaw and cheek for
      approximately one hour, leading to partial intake of tobacco constituents. To
      understand user exposure to tobacco, a multi-analyte approach based on the
      extraction of pouches by methanol, ethanol and water was validated and applied to
      the measurement of various constituents, including nicotine, four tobacco
      specific nitrosamines (TSNAs), propylene glycol, water, ammonium, nitrate,
      sodium, chloride, linalool, citronellol, linalyl acetate and geraniol, extracted
      from snus pouches during use by human consumers. RESULTS: After validation
      against established single-analyte methods, the multi-analyte approach was used
      to determine constituent levels in snus pouches before and after one hour of use.
      Although the concentrations in the snus pouches varied from nanogram (e.g. TSNAs)
      to milligram (e.g. nicotine, sodium and propylene glycol) quantities (25.1 ng to
      35.3 mg per 1 g pouch), the mean percentage extracted varied only from 19.2% for
      linalyl acetate to 37.8% for the TSNA 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) among all constituents analyzed. The TSNAs, some of which are
      known carcinogens, showed the highest percentage extraction (range 34.6%-37.8%).
      Measurement variability was low for all analytes, ranging from 2.4% (total TSNAs,
      NAT) to 9.5% (geraniol). By contrast, inter-subject variability ranged from 6.7%
      (NAB) to 52.2% (linalyl acetate), and was greater than 20% for eight of the
      constituents analyzed. Intra-subject variability ranged from 3.4% (citronellol)
      to 29.7% (geraniol). CONCLUSIONS: Generally, less than a third of each
      constituent tested was extracted during one hour of snus use, independent of
      constituent concentration. The variable nature of in-use extraction was shown to
      be driven by inter-subject variability. The results provide insight into possible
      mechanisms controlling constituent extraction in the mouth during snus use, and
      provide reference data for the development of in-vitro laboratory systems for
      estimating extraction of tobacco constituents from snus.

PMID- 23548062
TI  - Single application of 4% dimeticone liquid gel versus two applications of 1%
      permethrin creme rinse for treatment of head louse infestation: a randomised
      controlled trial.
AB  - BACKGROUND: A previous study indicated that a single application of 4% dimeticone
      liquid gel was effective in treating head louse infestation. This study was
      designed to confirm this in comparison with two applications of 1% permethrin.
      METHODS: We have performed a single centre parallel group, randomised,
      controlled, open label, community based trial, with domiciliary visits, in
      Cambridgeshire, UK. Treatments were allocated through sealed instructions derived
      from a computer generated list. We enrolled 90 children and adults with confirmed
      head louse infestation analysed by intention to treat (80 per-protocol after 4
      drop outs and 6 non-compliant). The comparison was between 4% dimeticone liquid
      gel applied once for 15 minutes and 1% permethrin creme rinse applied for 10
      minutes, repeated after 7 days as per manufacturer's directions. Evaluated by
      elimination of louse infestation after completion of treatment application
      regimen. RESULTS: Intention to treat comparison of a single dimeticone liquid gel
      treatment with two of permethrin gave success for 30/43 (69.8%) of the dimeticone
      liquid gel group and 7/47 (14.9%) of the permethrin creme rinse group (OR 13.19,
      95% CI 4.69 to 37.07) (p < 0.001). Per protocol results were similar with 27/35
      (77.1%) success for dimeticone versus 7/45 (15.6%) for permethrin. Analyses by
      household gave essentially similar outcomes. CONCLUSIONS: The study showed one 15
      minute application of 4% dimeticone liquid gel was superior to two applications
      of 1% permethrin creme rinse (p < 0.001). The low efficacy of permethrin suggests
      it should be withdrawn. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN88144046.

PMID- 23548065
TI  - Bio-inspired carbon nanotube-polymer composite yarns with hydrogen bond-mediated
      lateral interactions.
AB  - Polymer composite yarns containing a high loading of double-walled carbon
      nanotubes (DWNTs) have been developed in which the inherent acrylate-based
      organic coating on the surface of the DWNT bundles interacts strongly with
      poly(vinyl alcohol) (PVA) through an extensive hydrogen-bond network. This design
      takes advantage of a toughening mechanism seen in spider silk and collagen, which
      contain an abundance of hydrogen bonds that can break and reform, allowing for
      large deformation while maintaining structural stability. Similar to that
      observed in natural materials, unfolding of the polymeric matrix at large
      deformations increases ductility without sacrificing stiffness. As the PVA
      content in the composite increases, the stiffness and energy to failure of the
      composite also increases up to an optimal point, beyond which mechanical
      performance in tension decreases. Molecular dynamics (MD) simulations confirm
      this trend, showing the dominance of nonproductive hydrogen bonding between PVA
      molecules at high PVA contents, which lubricates the interface between DWNTs.

PMID- 23548063
TI  - The expression and regulation of matrix metalloproteinase-3 is critically
      modulated by Porphyromonas gingivalis lipopolysaccharide with heterogeneous lipid
      A structures in human gingival fibroblasts.
AB  - BACKGROUND: Porphyromonas gingivalis lipopolysaccharide (LPS) is a crucial
      virulence factor strongly associated with chronic periodontitis which is the
      primary cause of tooth loss in adults. It exhibits remarkable heterogeneity
      containing tetra-(LPS(1435/1449)) and penta-(LPS(1690)) acylated lipid A
      structures. Human gingival fibroblasts (HGFs) as the main resident cells of human
      gingiva play a key role in regulating matrix metalloproteinases (MMPs) and
      contribute to periodontal homeostasis. This study investigated the expression and
      regulation of MMPs1-3 and tissue inhibitors of MMP-1 (TIMP-1) in HGFs in response
      to P. gingivalis LPS(1435/1449) and LPS(1690) and hexa-acylated E. coli LPS as a
      reference. The expression of MMPs 1-3 and TIMP-1 was evaluated by real-time PCR
      and ELISA. RESULTS: The MMP-3 mRNA and protein were highly upregulated in P.
      gingivalis LPS(1690)- and E. coli LPS-treated cells, whereas no induction was
      observed in P. gingivalis LPS(1435/1449)-treated cells. On the contrary, the
      expression of MMP-1 and -2 was not significantly affected by P. gingivalis LPS
      lipid A heterogeneity. The TIMP-1 mRNA was upregulated in P. gingivalis
      LPS(1435/1449)- and E. coli LPS-treated cells. Next, signal transduction pathways
      involved in P. gingivalis LPS-induced expression of MMP-3 were examined by
      blocking assays. Blockage of p38 MAPK and ERK significantly inhibited P.
      gingivalis LPS(1690)-induced MMP-3 expression in HGFs. CONCLUSION: The present
      findings suggest that the heterogeneous lipid A structures of P. gingivalis LPS
      differentially modulate the expression of MMP-3 in HGFs, which may play a role in
      periodontal pathogenesis.

PMID- 23548066
TI  - Serum levels of intravitreal bevacizumab after vitrectomy, lensectomy and non
      surgical controls.
AB  - PURPOSE: To determine serum level differences of intravitreally-placed
      bevacizumab after vitrectomy and lensectomy-vitrectomy and to compare these with
      non-operated eyes in a rabbit model. METHODS: Five Dutch-belted rabbits underwent
      pars plana vitrectomy (PPV), five rabbits underwent pars plana lensectomy (PPL)
      and five rabbits served as non-surgical controls. Twelve days following the
      surgical procedures, each operated eye underwent an intravitreal injection
      consisting of 1.25 mg/0.05 mL bevacizumab. Serum levels from each rabbit were
      drawn on days 2, 4, 7, 10, 14, 21, 28 and 35 and were measured with ELISA
      immunoassay. RESULTS: The average peak serum concentration (Cmax) was highest for
      the PPL group (11.33 MUg +/- 3.48 mL), and was similar between the PPV (5.35 MUg
      +/- 2.69 mL) and non-surgical control groups (5.35 MUg +/- 0.69 mL). The average
      time to maximal plasma concentration (Tmax) in days was earliest for the PPL
      group (2.8 +/- 0.47), followed by the PPV (5.6 +/- 0.84) and non-surgical control
      groups (6.4 +/- 0.71). The PPL group had higher serum levels than the other two
      groups until day 7 that was significant only at day 2 (p < 0.0001). After day 4,
      there were no significant differences or trends between any of the three groups.
      The half-life (T1/2) was fastest for the PPL group (1.41 +/- 0.21 d) followed by
      the PPV (2.80 +/- 3.35 d) and non-surgical control groups (6.69 +/- 10.4 d).
      CONCLUSIONS: Serum bevacizumab levels were initially elevated following
      lensectomy and vitrectomy compared to non-surgical eyes following intravitreal
      injection. The half-life of bevacizumab was prolonged in non-surgical eyes
      presumably due to a slower release from the vitreous cavity.

PMID- 23548067
TI  - Acceleration of denitrification in turbid rivers due to denitrification occurring
      on suspended sediment in oxic waters.
AB  - High suspended sediment (SPS) concentration exists in many rivers of the world.
      In the present study, the effects of SPS concentration on denitrification were
      investigated in airtight chambers with sediment samples collected from the Yellow
      River which is the largest turbid river in the world. Results from the nitrogen
      stable ((15)N) isotopic tracer experiments showed that denitrification could
      occur on SPS in oxic waters and the denitrification rate increased with SPS
      concentration; this was probably caused by the presence of low-oxygen microsites
      in SPS. For the water systems with both bed-sediment and SPS, the denitrification
      kinetics fit well to Logistic model, and the denitrification rate constant
      increased linearly with SPS concentration (p < 0.01). The denitrification caused
      by the presence of SPS accounted for 22%, 38%, 53%, and 67% of the total
      denitrification in systems with 2.5, 8, 15, and 20 g L(-1) SPS, respectively. The
      activity of denitrifying bacteria in SPS was approximately twice that in bed
      sediment, and the denitrifying bacteria population showed an increasing trend
      with SPS concentration in both SPS and bed-sediment, leading to the increase of
      denitrification rate with SPS concentration. Furthermore, the denitrification in
      bed-sediment was accelerated by increased diffusion of nitrate from overlying
      water to bed-sediment under agitation conditions, which accompanied with the
      presence of SPS. When with 8 g L(-1) SPS, approximately 66% of the increased
      denitrification compared to that without SPS was attributed to denitrification on
      SPS and 34% to agitation conditions. This is the first report of the occurrence
      of denitrification on SPS in oxic waters. The results suggest that SPS plays an
      important role in denitrification in turbid rivers; its effect on nitrogen cycle
      should be considered in future study.

PMID- 23548068
TI  - Variation in endoglin pathway genes is associated with preeclampsia: a case
      control candidate gene association study.
AB  - BACKGROUND: Preeclampsia is a hypertensive, multi-system pregnancy disorder whose
      pathophysiology remains unclear. Elevations in circulating soluble endoglin
      (sENG) and placental/blood ENG mRNA expression antedate the clinical onset of
      preeclampsia. This study investigated if endoglin (ENG) pathway genetic variation
      was also associated with the development of preeclampsia. METHODS: We used a case
      control candidate gene association design. Data from 355 white (181 preeclampsia
      cases/174 controls) and 60 black (30 preeclampsia cases/30 controls) women
      matched on ancestry, age, and parity were analyzed. Tagging single nucleotide
      polymorphisms (tSNPs) and potentially functional SNPs in ENG, TGFbeta1,
      TGFbetaR1, ALK1, and TGFbetaR2 were genotyped with iPLEX(r) and TaqMan(r). Chi
      square or Fisher's exact tests were used to conduct allele/genotype/haplotype
      tests in white/black subgroups separately. Odds ratios were computed with binary
      logistic regression for tSNPs with significant genotype tests. RESULTS: Of the 49
      SNPs evaluated, variation in two ENG tSNPs (rs11792480, rs10121110) and one
      TGFbetaR2 tSNP (rs6550005) was associated with preeclampsia in white women (P
      <0.05, each). In black women, variation in two TGFbeta1 tSNPs (rs4803455,
      rs4803457), one TGFbetaR1 tSNP (rs10739778), and three TGFbetaR2 tSNPs
      (rs6550005, rs1346907, rs877572) was associated with preeclampsia (P <0.05,
      each). Further evaluation of ENG tSNP rs10121110 revealed that white women
      inheriting the AA genotype were 2.29 times more likely to develop preeclampsia
      compared to the GG genotype (P = 0.008, [99% CI: 1.02 to 5.13]). For black women,
      similar evaluation of TGFbeta1 tSNP rs4803457 revealed women inheriting the CT
      genotype were 7.44 times more likely to develop preeclampsia than those with the
      CC genotype (P = 0.005, [99% CI: 1.19 to 46.41]). CONCLUSIONS: ENG pathway
      genetic variation is associated with preeclampsia. Different ENG pathway genes
      may be involved in preeclampsia development among white and black women.
      Additional studies are needed to validate these findings and to determine if
      genetic variation in ENG pathway genes impacts ENG and sENG levels in
      preeclampsia.

PMID- 23548069
TI  - Young men's condom use resistance tactics: a latent profile analysis.
AB  - Research suggests that many men have used a variety of tactics to avoid using
      condoms when having sex with women. Guided by previous work demonstrating that
      men's use of coercive condom resistance tactics was predicted by negative
      attitudes toward women, inconsistent condom use, multiple partners, and sexual
      sensation seeking, the current study used latent profile analysis (LPA) to
      determine whether similar constructs were associated with a variety of resistance
      tactics. A community sample of 313 moderate-drinking men participated, of whom
      80% reported employing at least one condom use resistance tactic since
      adolescence. The LPA revealed three classes of men. In general, men with the
      least negative beliefs about women, low levels of sexual sensation seeking and
      impulsivity, and positive beliefs about condoms (Condom Positive/Low Hostility)
      reported less use of resistance tactics than men with moderate sexual sensation
      seeking and impulsivity, negative beliefs about condoms, and moderate (Condom
      Negative/Moderate Hostility) or high (Condom Negative/High Hostility) negative
      attitudes about women. The classes also differed in terms of their sexual
      behaviors. This study demonstrated that sexual risk behavior interventions should
      not only address the tactics through which men resist using condoms but also
      tailor these efforts to men's individual characteristics. 

PMID- 23548070
TI  - Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in
      peripheral blood of patients with gastric cancer.
AB  - BACKGROUND: We examined preoperative kinesin II-associated protein (KAP1), TIMP
      metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels
      in patients with gastric cancers to assess their clinical application for
      diagnosing and monitoring diseases. METHODS: Real-time reverse transcription
      polymerase chain reaction was used to detect the expression levels of KAP1,
      TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2)
      and secreted protein, acidic, cysteine-rich (SPARC) in the patients' peripheral
      blood karyocytes. The data were analyzed with receiver operating characteristics
      (ROC) curves. RESULTS: A total of 112 patients with gastric cancer, 42 patients
      with recurrence and 107 healthy volunteers were recruited. There were significant
      correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and
      distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 +/-
      0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 +/- 0.043 (P = 0.0001) and the AUC
      of STC2 was 0.769 +/- 0.045 (P = 0.0001), thus differentiating preoperative
      gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of
      STC2 was 0.739 +/- 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 +/- 0.088 (P =
      0.319), thus differentiating recurrence of gastric cancer from healthy volunteers
      by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be
      poor prognostic factors of disease recurrence in patients with gastric cancer.
      CONCLUSIONS: KAP1, TIMP1 and STC2 expression levels may be potential biomarkers
      for the screening, diagnosis, prognosis and surveillance of gastric cancer.

PMID- 23548071
TI  - Recent advances in mucosal immunization using virus-like particles.
AB  - Mucosal immunization offers the promises of eliciting a systemic and mucosal
      immune response, as well as enhanced patient compliance. Mucosal vaccination
      using defined antigens such as proteins and peptides requires delivery systems
      that combine good safety profiles with strong immunogenicity, which may be
      provided by virus-like particles (VLP). VLP are assembled from viral structural
      proteins and thus are devoid of any genetic material. They excel by mimicking
      natural pathogens, therefore providing antigen-protecting particulate nature,
      inherent immune-cell stimulatory mechanisms, and tissue-specific targeting
      depending on their parental virus. Nevertheless, despite of promising preclinical
      results, VLP remain rarely investigated in clinical studies. This review is
      intended to give an overview of obstacles and promises of VLP-based mucosal
      immunization as well as to identify strategies to further improve VLP while
      maintaining a good safety and tolerability profile.

PMID- 23548072
TI  - Temporal lobe discharges and glossolalia.
AB  - Glossolalia (speaking in tongues) is a religious phenomenon of which there has
      been only limited scientific investigation. Described here is the case of a 44
      year-old woman who had clonic jerking of the left forearm while speaking in
      tongues. Waking EEG while she was thinking of nothing in particular was normal.
      After several minutes of silently praying in tongues she manifested right
      temporal sharp wave discharges and may have been in a state resembling light
      sleep. Possible relationships between glossolalia, ecstatic religious phenomena,
      and temporal lobe electrical discharges are discussed. 

PMID- 23548074
TI  - Diastereoselective reaction of sulfoxonium ylides, aldehydes and ketenes: an
      approach to trans-gamma-lactones.
AB  - In this paper, a novel approach to gamma-lactones from the reaction of
      sulfoxonium ylides, aldehydes, and ketenes is described. The new ylide-based
      method provides access to gamma-lactones from disubstituted ketenes, in good
      yields, and with good diastereoselectivity favoring the trans-diastereomer (11
      examples with dr >= 82:18, dr up to 92:8).

PMID- 23548073
TI  - The supramolecular chemistry of beta-sheets.
AB  - Interactions among beta-sheets occur widely in protein quaternary structure,
      protein-protein interaction, and protein aggregation and are central in
      Alzheimer's and other amyloid-related diseases. This Perspective looks at the
      structural biology of these important yet under-appreciated interactions from a
      supramolecular chemist's point of view. Common themes in the supramolecular
      interactions of beta-sheets are identified and richly illustrated though examples
      from proteins, amyloids, and chemical model systems. beta-Sheets interact through
      edge-to-edge hydrogen bonding to form extended layers and through face-to-face
      hydrophobic or van der Waals interactions to form layered sandwich-like
      structures. Side chains from adjacent layers can fit together through simple
      hydrophobic contacts or can participate in complementary interdigitation or knob
      hole interactions. The layers can be aligned, offset, or rotated. The right
      handed twist of beta-sheets provides additional opportunities for stabilization
      of edge-to-edge contacts and rotated layered structures.

PMID- 23548075
TI  - Developing research in partnership with Aboriginal communities - strategies for
      improving recruitment and retention.
AB  - CONTEXT: Australian Aboriginal communities in urban, rural and remote areas are
      continuing to suffer high rates of perinatal mortality and morbidity that will
      impact on the future health of the community. It has been well documented that
      Aboriginal women have extreme distrust of mainstream pregnancy-related health
      care and suggested that late entry into antenatal care is as high as 50% in the
      Aboriginal population. Although medical and midwifery staff have long discussed
      strategies to improve uptake of antenatal health care for Aboriginal women,
      researchers in many areas have found the recruitment of Aboriginal people into
      scientific studies almost impossible. This article seeks to share the strategies
      that have been developed over a period of time by the authors that have proved
      useful for recruitment and retention into research. It is anticipated that these
      strategies would also apply for health practitioners in maintaining their
      patients for clinical care management. ISSUE: Although each research location
      (regional, rural and remote) has had to spend time determining what approach is
      best for meeting the research outcomes, many of these suggestions become
      applicable to clinicians seeking to develop better connections with Aboriginal
      patients in their clinics. With the management of ongoing chronic health
      conditions for Aboriginal people a priority in 'Closing the Gap', a number of
      these suggestions could easily be implemented by clinicians. Remembering that
      each community has specific needs that must be addressed, priorities for
      assistance for that community will be easily identifiable after community
      consultation (eg transport, or ability to access medical testing). Opportunities
      for the use of new social media (eg Facebook) as communication tools for
      researchers and clinicians will have increasing applicability as further software
      updates are created. LESSONS LEARNT: With open and trusting dialogues between
      researchers, clinicians and Aboriginal communities, we can go a long way towards
      understanding the needs of individual communities and working in partnerships to
      close the gap.

PMID- 23548076
TI  - Optically and electrically driven organic thin film transistors with diarylethene
      photochromic channel layers.
AB  - We achieved drain-current switching of diarylethene-channel field-effect
      transistors with light- and electric-field effects. The drain current was
      reversibly changed by alternating ultraviolet and visible light irradiation.
      Stress is placed on the fact that the on/off ratio realized by light irradiation
      was 1 * 10(2) (1 * 10(4)%) and this value is much larger than those in other
      photochromism-based transistors. These results indicate that the drain current
      was effectively controlled by light irradiation. Furthermore, the on and off
      states modulated by light were maintained without light irradiation even after 1
      week, exhibiting that our transistor works as an optical memory. We clarified
      that the light-driven modulation can be attributed to the transformation in the
      pi-conjugation system accompanied by photoisomerization. These findings have the
      potential to attain high-performance optoelectrical organic devices including
      optical sensors, optical memory, and photoswitching transistors.

PMID- 23548077
TI  - Rhesus macaques vaccinated with consensus envelopes elicit partially protective
      immune responses against SHIV SF162p4 challenge.
AB  - The development of a preventative HIV/AIDS vaccine is challenging due to the
      diversity of viral genome sequences, especially in the viral envelope (Env160).
      Since it is not possible to directly match the vaccine strain to the vast number
      of circulating HIV-1 strains, it is necessary to develop an HIV-1 vaccine that
      can protect against a heterologous viral challenge. Previous studies from our
      group demonstrated that a mixture of wild type clade B Env(gp160s) were able to
      protect against a heterologous clade B challenge more effectively than a
      consensus clade B Envg(p160) vaccine. In order to broaden the immune response to
      other clades of HIV, in this study rhesus macaques were vaccinated with a
      polyvalent mixture of purified HIV-1 trimerized consensus Envg(p140) proteins
      representing clades A, B, C, and E. The elicited immune responses were compared
      to a single consensus Env(gp140) representing all isolates in group M (Con M).
      Both vaccines elicited anti- Env(gp140) IgG antibodies that bound an equal number
      of HIV-1 Env(gp160) proteins representing clades A, B and C. In addition, both
      vaccines elicited antibodies that neutralized the HIV-1(SF162) isolate. However,
      the vaccinated monkeys were not protected against SHIV(SF162p4) challenge. These
      results indicate that consensus Env(gp160) vaccines, administered as purified
      Env(gp140) trimers, elicit antibodies that bind to Env(gp160s) from strains
      representing multiple clades of HIV-1, but these vaccines did not protect against
      heterologous SHIV challenge.

PMID- 23548078
TI  - Acid-soluble internal capsules for closed-face cassette elemental sampling and
      analysis of workplace air.
AB  - Airborne particles that are collected using closed-face filter cassettes (CFCs),
      which are used widely in the sampling of workplace aerosols, can deposit in
      places other than on the filter and thereby may not be included in the ensuing
      analysis. A technique for ensuring that internal non-filter deposits are included
      in the analysis is to collect airborne particles within an acid-soluble internal
      capsule that, following sampling, can be dissolved along with the filter for
      subsequent elemental analysis. An interlaboratory study (ILS) was carried out to
      evaluate the use of cellulosic CFC capsule inserts for their suitability in the
      determination of trace elements in airborne samples. The ILS was performed in
      accordance with an applicable ASTM International standard practice, ASTM E691,
      which describes statistical procedures for investigating interlaboratory
      precision. Performance evaluation materials consisted of prototype cellulose
      acetate capsules attached to mixed-cellulose ester filters. Batches of capsules
      were dosed with Pb-containing materials (standard aqueous solutions, and
      certified reference material soil and paint). Also, aerosol samples containing
      nine target analyte elements (As, Cd, Co, Cr, Cu, Fe, Pb, Mn, and Ni) were
      generated using a multiport sampler; various concentrations and sampling times
      were employed to yield samples fortified at desired loading levels. Triplicates
      of spiked capsules at three different loadings were conveyed to each volunteer
      laboratory; loading levels were unknown to the participants. The laboratories
      were asked to prepare the samples by acid dissolution and to analyze aliquots of
      extracted samples by atomic spectrometry in accordance with applicable ASTM
      International Standards. Participants were asked to report their results in units
      of MUg of each target element per sample. For the elements investigated, inter
      laboratory precision and recovery estimates from the participating laboratories
      demonstrated the utility of the cellulosic capsule inserts for the measurement of
      sampled trace elements.

PMID- 23548079
TI  - Determination of the content of rosmarinic acid by HPLC and analytical comparison
      of volatile constituents by GC-MS in different parts of Perilla frutescens (L.)
      Britt.
AB  - BACKGROUND: Perilla frutescens (L.) Britt. is not only an edible plant but also a
      traditional medicinal plant commonly used for treating common cold. It is widely
      cultivated in southern China. The anatomical parts of P. frutescens that are
      recorded as medicines in the Chinese material medica are: Perillae Caulis,
      Perillae Folium and Perillae Fructus, which are the dried stems, the dried leaves
      and the dried ripe fruits, respectively. Rosmarinic acid is one of major
      polyphenolic ingredients found in all three Perillae Caulis, Perillae Folium and
      Perillae Fructus. The characteristic volatile oil of P. frutescens is believed to
      be another essential composition of the herb, giving its wide range of use.
      RESULTS: A simple, rapid and accurate HPLC-DAD method was set up, suitable for
      the assay of rosmarinic acid in Perillae Fructus, Perillae Folium and Perillae
      Caulis. 12 batches of Perillae Caulis, 12 batches of Perillae Folium and 13
      batches of Perillae Fructus from 8 different regions of mainland China and Hong
      Kong herbal markets were collected for evaluating the quality of P. frutescens.
      Results showed that Perillae Folium typically had the highest content of
      rosmarinic acid. Certain macroscopic characteristics were related to the
      concentration of rosmarinic acid. The volatile components were identified and
      compared in Perillae Fructus, Perillae Folium and Perillae Caulis by gas
      chromatography-mass spectrometry (GC-MS). Extracts were prepared by steam
      distillation. Twelve, seventeen and nine compounds were identified and accounted
      for 69.71%, 50.54% and 81.73% of all identified peak areas in Perillae Caulis,
      Perillae Folium and Perillae Fructus respectively. The identified components were
      analyzed for comparison of Perillae Caulis, Perillae Folium and Perillae Fructus
      more effectively. CONCLUSIONS: This work provides a means by which samples of
      various parts of P. frutescens can be evaluated in terms of their
      pharmacologically active components. It should be of value in the efficient
      exploitation of P. frutescens plant material in clinical applications and drug
      development.

PMID- 23548080
TI  - Dracaena arborea alleviates ultra-structural spermatogenic alterations in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Infertility is a common complication in diabetic men and experimental
      animals, mainly due to loss of germ cells by apoptotic cell death. The aim of
      this study was to evaluate the effects of aqueous and ethanol extracts of
      Dracaena arborea in streptozotocin-induced ultra-structural spermatogenic
      alterations in Wistar rats. METHODS: Diabetic animals were orally treated with
      Millipore water (10 ml/kg), sildenafil citrate (1.44 mg/kg) or Dracaena arborea
      aqueous (500 mg/kg) and ethanol (100 mg/kg) extracts for three weeks. A group of
      non diabetic rats received Millipore water (10 ml/kg) and served as healthy
      control group. Blood glucose was monitored at the beginning and the end of the
      study. One day after the last treatment, animals were sacrificed and the testes
      immediately removed were morphologically observed and prepared for electron
      microscopy analysis of spermatogenesis. RESULTS: Our results showed that Dracaena
      arborea was devoid of any anti-hyperglycemic activity. In the untreated diabetic
      rats, hyperglycemia severely damaged the testes morphology as well as the
      spermatogenic process as evidenced by the: thickness of basement membrane of the
      seminiferous tubule; mitochondria alteration; abnormal spermatocyte cells
      displaying polymorphous nuclei, cytoplasmic vacuolization and necrosis; and
      disorganization and degeneration of sperm germ cells. Administration of
      sildenafil citrate and Dracaena arborea extracts to the diabetic rats improved
      testes morphology and reversed, although not completely, the impairment of
      spermatogenesis; this alleviating effect was more pronounced in animals treated
      with the aqueous extract (500 mg/kg) of Dracaena arborea. CONCLUSION: Dracaena
      arborea improves testes morphology and restores spermatogenesis in type 1
      diabetic rats, without having major anti-hyperglycemic properties. These effects
      could be attributed to saponins, flavonoids, phenols and sterols revealed in this
      plant, which could be a useful component in the treatment of diabetes-induced
      testicular dysfunction.

PMID- 23548081
TI  - Mealybugs nested endosymbiosis: going into the 'matryoshka' system in Planococcus
      citri in depth.
AB  - BACKGROUND: In all branches of life there are plenty of symbiotic associations.
      Insects are particularly well suited to establishing intracellular symbiosis with
      bacteria, providing them with metabolic capabilities they lack. Essential primary
      endosymbionts can coexist with facultative secondary symbionts which can,
      eventually, establish metabolic complementation with the primary endosymbiont,
      becoming a co-primary. Usually, both endosymbionts maintain their cellular
      identity. An exception is the endosymbiosis found in mealybugs of the subfamily
      Pseudoccinae, such as Planococcus citri, with Moranella endobia located inside
      Tremblaya princeps. RESULTS: We report the genome sequencing of M. endobia str.
      PCVAL and the comparative genomic analyses of the genomes of strains PCVAL and
      PCIT of both consortium partners. A comprehensive analysis of their functional
      capabilities and interactions reveals their functional coupling, with many cases
      of metabolic and informational complementation. Using comparative genomics, we
      confirm that both genomes have undergone a reductive evolution, although with
      some unusual genomic features as a consequence of coevolving in an exceptional
      compartmentalized organization. CONCLUSIONS: M. endobia seems to be responsible
      for the biosynthesis of most cellular components and energy provision, and
      controls most informational processes for the consortium, while T. princeps
      appears to be a mere factory for amino acid synthesis, and translating proteins,
      using the precursors provided by M. endobia. In this scenario, we propose that
      both entities should be considered part of a composite organism whose
      compartmentalized scheme (somehow) resembles a eukaryotic cell.

PMID- 23548082
TI  - Variation in ultraviolet radiation and diabetes: evidence of an epigenetic effect
      that modulates diabetics' lifespan.
AB  - BACKGROUND: Published research has shown that month-of-birth variations modulate
      the incidence of adult human diseases. This article explores diabetes type 2 as
      one of those diseases. This study uses the death records of approximately 829,000
      diabetics (approximately 90% were type-2) born before the year 1945 (and dying
      between 1979 and 2005) to show that variations in adult lifespan vary with
      ultraviolet radiation (UVR) at solar cycle peaks (MAX, approximately a three-year
      period) with less at non-peaks (MIN, approximately an eight-year period). The MAX
      minus MIN (in years) was our measure of sensitivity (for example, responsiveness)
      to long-term variations in UVR. RESULTS: Diabetics were less sensitive than non
      diabetics, and ethnic minorities were more sensitive than whites. Diabetic males
      gained 6.1 years, and females 2.3 years over non-diabetics, with diabetic males
      gaining an average of 3.8 years over diabetic females. Most variation in lifespan
      occurred in those conceived around the seasonal equinoxes, suggesting that the
      human epigenome at conception is especially influenced by rapid variation in UVR.
      With rapidly decreasing UVR at conception, lifespan decreased in the better
      nourished, white, female diabetic population. CONCLUSIONS: Rapidly changing UVR
      at the equinoxes modulates the expression of an epigenome involving the
      conservation of energy, a mechanism especially canalized in women. Decreasing UVR
      at conception and early gestation stimulates energy conservation in persons we
      consider 'diabetic' in today's environment of caloric surfeit. In the late 19th
      and early 20th centuries ethnic minorities had poorer nutrition, laborious work,
      and leaner bodies, and in that environment a calorie-conserving epigenome was a
      survival advantage. Ethnic minorities with a similar epigenome lived long enough
      to express diabetes as we define it today and exceeded the lifespan of their non
      diabetic contemporaries, while that epigenome in diabetics in the nutritional
      environment of today is detrimental to lifespan.

PMID- 23548083
TI  - Biomass-derived sponge-like carbonaceous hydrogels and aerogels for
      supercapacitors.
AB  - As a newly developed material, carbon gels have been receiving considerable
      attention due to their multifunctional properties. Herein, we present a facile,
      green, and template-free route toward sponge-like carbonaceous hydrogels and
      aerogels by using crude biomass, watermelon as the carbon source. The obtained
      three-dimensional (3D) flexible carbonaceous gels are made of both carbonaceous
      nanofibers and nanospheres. The porous carbonaceous gels (CGs) are highly
      chemically active and show excellent mechanical flexibility which enable them to
      be a good scaffold for the synthesis of 3D composite materials. We synthesized
      the carbonaceous gel-based composite materials by incorporating Fe3O4
      nanoparticles into the networks of the carbonaceous gels. The Fe3O4/CGs
      composites further transform into magnetite carbon aerogels (MCAs) by
      calcination. The MCAs keep the porous structure of the original CGs, which allows
      the sustained and stable transport of both electrolyte ions and electrons to the
      electrode surface, leading to excellent electrochemical performance. The MCAs
      exhibit an excellent capacitance of 333.1 F.g(-1) at a current density of 1 A.g(
      1) within a potential window of -1.0 to 0 V in 6 M KOH solution. Meanwhile, the
      MCAs also show outstanding cycling stability with 96% of the capacitance
      retention after 1000 cycles of charge/discharge. These findings open up the use
      of low-cost elastic carbon gels for the synthesis of other 3D composite materials
      and show the possibility for the application in energy storage.

PMID- 23548084
TI  - Recent developments in Blastocystis research.
AB  - Blastocystis is a common parasite of the human large intestine but has an
      uncertain role in disease. In this review, we appraise the published evidence
      addressing this and its weaknesses. Genetic diversity studies have led to the
      identification of numerous subtypes (STs) within the genus Blastocystis and,
      recently, methods for studying variation within STs have been developed, with
      implications for our understanding of host specificity. The geographic
      distribution of STs is summarised and the impact this may have on investigations
      into the role of the organism in disease is discussed. Finally, we describe the
      organelle and nuclear genome characteristics and look to future developments in
      the field.

PMID- 23548085
TI  - Tradition and transition: parasitic zoonoses of people and animals in Alaska,
      northern Canada, and Greenland.
AB  - Zoonotic parasites are important causes of endemic and emerging human disease in
      northern North America and Greenland (the North), where prevalence of some
      parasites is higher than in the general North American population. The North
      today is in transition, facing increased resource extraction, globalisation of
      trade and travel, and rapid and accelerating environmental change. This
      comprehensive review addresses the diversity, distribution, ecology,
      epidemiology, and significance of nine zoonotic parasites in animal and human
      populations in the North. Based on a qualitative risk assessment with criteria
      heavily weighted for human health, these zoonotic parasites are ranked, in the
      order of decreasing importance, as follows: Echinococcus multilocularis,
      Toxoplasma gondii, Trichinella and Giardia, Echinococcus granulosus/canadensis
      and Cryptosporidium, Toxocara, anisakid nematodes, and diphyllobothriid cestodes.
      Recent and future trends in the importance of these parasites for human health in
      the North are explored. For example, the incidence of human exposure to endemic
      helminth zoonoses (e.g. Diphyllobothrium, Trichinella, and Echinococcus) appears
      to be declining, while water-borne protozoans such as Giardia, Cryptosporidium,
      and Toxoplasma may be emerging causes of human disease in a warming North.
      Parasites that undergo temperature-dependent development in the environment (such
      as Toxoplasma, ascarid and anisakid nematodes, and diphyllobothriid cestodes)
      will likely undergo accelerated development in endemic areas and temperate
      adapted strains/species will move north, resulting in faunal shifts. Food-borne
      pathogens (e.g. Trichinella, Toxoplasma, anisakid nematodes, and diphyllobothriid
      cestodes) may be increasingly important as animal products are exported from the
      North and tourists, workers, and domestic animals enter the North. Finally, key
      needs are identified to better assess and mitigate risks associated with zoonotic
      parasites, including enhanced surveillance in animals and people, detection
      methods, and delivery and evaluation of veterinary and public health services.

PMID- 23548087
TI  - Microsporidia and 'the art of living together'.
AB  - Parasitism, aptly defined as one of the 'living-together' strategies (Trager,
      1986), presents a dynamic system in which the parasite and its host are under
      evolutionary pressure to evolve new and specific adaptations, thus enabling the
      coexistence of the two closely interacting partners. Microsporidia are very
      frequently encountered obligatory intracellular protistan parasites that can
      infect both animals and some protists and are a consummate example of various
      aspects of the 'living-together' strategy. Microsporidia, relatives of fungi in
      the superkingdom Opisthokonta, belong to the relatively small group of parasites
      for which the host cell cytoplasm is the site of both reproduction and
      maturation. The structural and physiological reduction of their vegetative stage,
      together with the manipulation of host cell physiology, enables microsporidia to
      live in the cytosolic environment for most of their life cycle in a way
      resembling endocytobionts. The ability to form structurally complex spores and
      the invention and assembly of a unique injection mechanism enable microsporidia
      to disperse within host tissues and between host organisms, resulting in long
      lasting infections. Microsporidia have adapted their genomes to the intracellular
      way of life, evolved strategies how to obtain nutrients directly from the host
      and how to manipulate not only the infected cells, but also the hosts themselves.
      The enormous variability of host organisms and their tissues provide
      microsporidian parasites a virtually limitless terrain for diversification and
      ecological expansion. This review attempts to present a general overview of
      microsporidia, emphasising some less known and/or more recently discovered facets
      of their biology.

PMID- 23548086
TI  - The malaria transition on the Arabian Peninsula: progress toward a malaria-free
      region between 1960-2010.
AB  - The transmission of malaria across the Arabian Peninsula is governed by the
      diversity of dominant vectors and extreme aridity. It is likely that where
      malaria transmission was historically possible it was intense and led to a high
      disease burden. Here, we review the speed of elimination, approaches taken,
      define the shrinking map of risk since 1960 and discuss the threats posed to a
      malaria-free Arabian Peninsula using the archive material, case data and
      published works. From as early as the 1940s, attempts were made to eliminate
      malaria on the peninsula but were met with varying degrees of success through to
      the 1970s; however, these did result in a shrinking of the margins of malaria
      transmission across the peninsula. Epidemics in the 1990s galvanised national
      malaria control programmes to reinvigorate control efforts. Before the launch of
      the recent global ambition for malaria eradication, countries on the Arabian
      Peninsula launched a collaborative malaria-free initiative in 2005. This
      initiative led a further shrinking of the malaria risk map and today locally
      acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen,
      with the latter contributing to over 98% of the clinical burden.

PMID- 23548088
TI  - Patterns and processes in parasite co-infection.
AB  - Co-infection of individual hosts by multiple parasite species is a pattern that
      is very commonly observed in natural populations. Understanding the processes
      that generate these patterns poses a challenge. For example, it is difficult to
      discern the relative roles of exposure and susceptibility in generating the
      mixture and density of parasites within hosts. Yet discern them we must, if we
      are to design and deliver successful medical interventions for co-infected
      populations. Here, we synthesise an emergent understanding of how processes
      operate and interact to generate patterns of co-infection. We consider within
      host communities (or infracommunities) generally, that is including not only
      classical parasites but also the microbiota that are so abundant on mucosal
      surfaces and which are increasingly understood to be so influential on host
      biology. We focus on communities that include a helminth, but we expect similar
      inferences to pertain to other taxa. We suggest that, thanks to recent research
      at both the within-host (e.g. immunological) and between-host (e.g.
      epidemiological) scales, researchers are poised to reveal the processes that
      generate the observed distribution of parasite communities among hosts. Progress
      will be facilitated by using new technologies as well as statistical and
      experimental tools to test competing hypotheses about processes that might
      generate patterns in co-infection data. By understanding the multiple
      interactions that underlie patterns of co-infection, we will be able to
      understand and intelligently predict how a suite of co-infections (and thus the
      host that bears them) will together respond to medical interventions as well as
      other environmental changes. The challenge for us all is to become scholars of co
      infections.

PMID- 23548089
TI  - Infertility and assisted reproduction: counselling and psychosocial aspects.

PMID- 23548090
TI  - Do nurses and midwives have a role in promoting the well-being of patients during
      their fertility journey? A review of the literature.
AB  - People seeking fertility treatment are exposed to numerous stressors and many
      professionals are involved in their care. This literature review focuses on the
      role of nurses and midwives in the promotion of patient's well-being. Key themes
      identified are the need for continuity of care and support at all stages of
      treatment, but particularly prior to pregnancy testing, during the ante-natal
      period and following unsuccessful treatment. Women who conceive through fertility
      treatment are often anxious about the risk of potential miscarriage. It is not
      unreasonable that nurses and midwives receive training in acquiring skills in the
      provision of such support to patients which, arguably, is consistent with the
      general requirement that their skills and knowledge are updated to ensure safe
      and effective practice, but this would have resource implications. The wider
      question of who should provide well-being and emotional support for patients is
      an area of reproductive medicine which requires further research.

PMID- 23548091
TI  - "You can always adopt": what clinic staff need to know about adoption and
      fostering?
AB  - This paper presents information and research about adoption and fostering, and
      explains some of the relevant processes. In order that those providing
      infertility services can play an informed, supportive and empowering role in the
      decision-making of those whose infertility treatment has been unsuccessful, a
      number of issues are highlighted. These include the changing profile of children
      awaiting adoption and fostering; ongoing contact between children and their birth
      families; the adoption of children from abroad; moving from infertility treatment
      to adoption or fostering; and the potential ongoing impact of infertility and
      failed treatment.

PMID- 23548092
TI  - The anxiety of infertility: the role of the nurses in the fertility clinic.
AB  - This paper discusses the effects of anxiety and depression on infertile people as
      they undergo infertility investigations and treatments, and explores what nurses
      may do to assist them to cope with this anxiety. There is an extensive literature
      on the psychosocial effects of infertility on couples, women and men separately
      and their children, but the nursing and midwifery literature lacks an in-depth
      exploration of the psychological and emotional consequences of infertility for
      infertile people. The paper concludes by arguing that nurses and midwives need to
      undertake research into their practice in fertility care, that is, caring for
      infertile people as they undergo assisted reproductive technologies and, to this
      end, suggests sources of research funding.

PMID- 23548093
TI  - Anonymous or known donors? A brief discussion of the psychosocial issues raised
      by removing anonymity from sperm donors.
AB  - In spite of a trend towards open identity, the ethical issues raised by the
      removal of anonymity from sperm donors are still contentious and raise
      controversy about the significance of genetic inheritance and what are often seen
      as competing rights claims for the children born, for donors and for the parents
      of donor insemination (DI) offspring. This review provides a short discussion of
      the arguments for and against the disclosure of donor insemination status to
      offspring, which are at the heart of the controversy over anonymity as they
      relate to the stakeholders in the process.

PMID- 23548094
TI  - Developments in infertility counselling and its accreditation.
AB  - Infertility counselling was placed in a unique position by the passage of the
      Human Fertilisation and Embryology Act 1990 and the requirement that couples
      being treated should be offered counselling. However professional counselling
      was, and largely still is, at a stage at which there was no universal agreement
      on the knowledge, standards or qualifications required for practice.
      Nevertheless, infertility counselling became the first example of counselling to
      be required by statute, beyond the more generalised requirement in adoption birth
      records access. Counselling is intended to describe skilled talking therapy
      offered by a professional with specific training and qualifications directed to
      helping individuals and couples to achieve goals they own themselves. The
      therapeutic intervention of counselling is primarily directed to helping clients
      in a stressful situation to deploy their own coping skills effectively and thus
      make the difficult choices inseparable from ART. Counselling outcome research
      consistently demonstrates the effectiveness of the sort of counselling delivered
      in assisted conception units with mild-moderate anxiety and depression delivered
      by skilled and experienced practitioners. This article reviews the role of
      counsellors as members of the assisted conception clinical team and the status of
      regulation and accreditation in this very new profession.

PMID- 23548095
TI  - British Infertility Counselling Association--Guidelines for good practice in
      infertility counselling. Third edition 2012.

PMID- 23548096
TI  - For your eyes only: bio-behavioural and psycho-social research priorities.
AB  - Infertility is experienced as a deeply personal and private condition, which has
      been investigated across disciplines, from psycho-social to bio-behavioural (van
      den Akker, 2012). This is undoubtedly, in part, because the interactions between
      the biological-behavioural axis and psychological-social axis have been linked to
      aetiological and treatment factors and to the consequences of infertility. Recent
      data from the Human Fertilization and Embryology Authority (HFEA, 2012) show that
      medically assisted reproduction (MAR) for infertility is continuing to increase,
      with 46,000 women in the UK seeking treatment in 2010 alone. Infertility is
      therefore considered to be a public health concern. However, prevention and
      ethical treatment require individual and collective responsibility. The currently
      identified public health concerns are compounded by evidence that genetic factors
      are linked to infertility, with new generations of children conceived through
      IVF/ICSI potentially affected by inherited damaged DNA (Bonde et al., 2008) that
      would otherwise not have found its way into the gene pool of new generations.
      Since treatment takes place at one point in time, and consideration of the moral
      rights and wrongs of the consequences of some treatments takes place at another,
      usually much later on within the social contexts in which they coexist with
      others, there is a discontinuity between the initial treatment and the future
      consequences of these treatments. In this paper I propose a simple prevention
      outcome consequences (POC) model for future comprehensive research priorities
      with substantial policy and practice implications. The time has come to face the
      new challenges with all eyes wide open.

PMID- 23548097
TI  - Impact of office productivity cloud computing on energy consumption and
      greenhouse gas emissions.
AB  - Cloud computing is usually regarded as being energy efficient and thus emitting
      less greenhouse gases (GHG) than traditional forms of computing. When the energy
      consumption of Microsoft's cloud computing Office 365 (O365) and traditional
      Office 2010 (O2010) software suites were tested and modeled, some cloud services
      were found to consume more energy than the traditional form. The developed model
      in this research took into consideration the energy consumption at the three main
      stages of data transmission; data center, network, and end user device.
      Comparable products from each suite were selected and activities were defined for
      each product to represent a different computing type. Microsoft provided highly
      confidential data for the data center stage, while the networking and user device
      stages were measured directly. A new measurement and software apportionment
      approach was defined and utilized allowing the power consumption of cloud
      services to be directly measured for the user device stage. Results indicated
      that cloud computing is more energy efficient for Excel and Outlook which
      consumed less energy and emitted less GHG than the standalone counterpart. The
      power consumption of the cloud based Outlook (8%) and Excel (17%) was lower than
      their traditional counterparts. However, the power consumption of the cloud
      version of Word was 17% higher than its traditional equivalent. A third mixed
      access method was also measured for Word which emitted 5% more GHG than the
      traditional version. It is evident that cloud computing may not provide a unified
      way forward to reduce energy consumption and GHG. Direct conversion from the
      standalone package into the cloud provision platform can now consider energy and
      GHG emissions at the software development and cloud service design stage using
      the methods described in this research.

PMID- 23548098
TI  - Follicle-stimulating hormone responsiveness in antral follicles from aryl
      hydrocarbon receptor knockout mice.
AB  - BACKGROUND: Previous studies have demonstrated that pre-pubertal aryl hydrocarbon
      receptor knockout (AHRKO) mice have slow antral follicle growth and reduced
      capacity to produce estradiol compared to wild-type (WT) mice. Although previous
      studies have suggested that this is likely due to a reduced ability of the AHRKO
      follicles to respond to follicle-stimulating hormone (FSH), this possibility was
      not directly tested. Thus, the goal of these studies was to test the hypothesis
      that low FSH responsiveness is responsible for the slow growth and reduced
      estradiol production observed in pre-pubertal AHRKO versus WT antral follicles.
      METHODS: Antral follicles from WT and AHRKO mice were cultured with varying
      amounts of FSH (0-15 IU/mL) for up to 7 days, and subjected to measurements of
      growth, FSH receptor and steroidogenic regulator expression, sex steroid hormone
      levels, and inhibin beta-A expression. General linear models (GLM) for repeated
      measures were used to compare follicle diameters over time among treatments. If
      the global tests from GLM were significant, Tukey's tests were used for pairwise
      comparisons. Remaining comparisons among groups were performed using one-way
      analysis of variance followed by Tukey's post hoc test. RESULTS: The results
      indicate that FSH stimulated growth in both WT and AHRKO follicles, but that high
      levels of FSH (10-15 IU/mL) were required for AHRKO follicles to reach maximal
      growth, whereas lower levels of FSH (5 IU/mL) were required for WT follicles to
      reach maximal growth. Further, FSH stimulated expression of FSH receptor,
      steroidogenic factors, and inhibin beta-A as well as production of steroid
      hormones in both WT and AHRKO follicles, but the degree of stimulation differed
      between WT and AHRKO follicles. Interestingly, FSH treatment increased expression
      of FSH receptor, some steroidogenic regulators, inhibin beta-A, and steroid
      hormone production more in AHRKO follicles compared to WT follicles. CONCLUSIONS:
      Collectively, these data suggest that the slow growth, but not reduced
      steroidogenesis in AHRKO follicles, is due to their reduced ability to respond to
      FSH compared to WT follicles. These data also suggest that the AHR may contribute
      to the ability of FSH to stimulate proper follicle growth, but it may not
      contribute to FSH-induced steroidogenesis.

PMID- 23548099
TI  - Cortical reorganization in multiple sclerosis after intrathecal baclofen therapy.
AB  - Our objective was to assess the role of Intrathecal Baclofen Therapy (ITB) in the
      cortical reorganization in a patient affected by multiple sclerosis (MS)
      undergoing physical therapy. We reported a case of a woman affected by MS and
      severe spasticity, who performed an fMRI examination, before and after the ITB
      implantation. The subject showed controlateral motor cortex activation after
      motor task. After a month of ITB implantation, patient showed ipsilateral and
      controlateral motor cortex activation although with a broader extension. fMRI
      examination supported the hypothesis of a central influence in patients who
      undergo physiotherapy and therapy with ITB. 

PMID- 23548100
TI  - Toehold-mediated nonenzymatic DNA strand displacement as a platform for DNA
      genotyping.
AB  - Toehold-mediated DNA strand displacement provides unique advantages in the
      construction and manipulation of multidimensional DNA nanostructures as well as
      nucleic acid sequence analysis. We demonstrate a step change in the use of
      toehold-mediated DNA strand displacement reactions, where a double-stranded DNA
      duplex, containing a single-stranded toehold domain, enzymatically generated and
      then treated as a molecular target for analysis. The approach was successfully
      implemented for human DNA genotyping, such as gender identification where the
      amelogenin gene was used as a model target system, and detecting single
      nucleotide polymorphisms of human mitochondrial DNA. Kinetics of the strand
      displacement was monitored by the quenched Forster resonance energy transfer
      effect.

PMID- 23548101
TI  - [18F]FDG and [18F]FLT positron emission tomography imaging following treatment
      with belinostat in human ovary cancer xenografts in mice.
AB  - BACKGROUND: Belinostat is a histone deacetylase inhibitor with anti-tumor effect
      in several pre-clinical tumor models and clinical trials. The aim of the study
      was to evaluate changes in cell proliferation and glucose uptake by use of 3'
      deoxy-3'-[(18)F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[(18)F]fluoro-D-glucose
      ([18F]FDG) positron emission tomography (PET) following treatment with belinostat
      in ovarian cancer in vivo models. METHODS: In vivo uptake of [18F]FLT and
      [18F]FDG in human ovary cancer xenografts in mice (A2780) were studied after
      treatment with belinostat. Mice were divided in 2 groups receiving either
      belinostat (40 mg/kg ip twice daily Day 0-4 and 6-10) or vehicle. Baseline
      [18F]FLT or [18F]FDG scans were made before treatment (Day 0) and repeated at Day
      3, 6 and 10. Tracer uptake was quantified using small animal PET/CT. RESULTS:
      Tumors in the belinostat group had volumes that were 462 +/- 62% (640 mm(3)) at
      Day 10 relative to baseline which was significantly different (P = 0.011) from
      the control group 769 +/- 74% (926 mm(3)). [18F]FLT SUVmax increased from
      baseline to Day 10 (+30 +/- 9%; P = 0.048) in the control group. No increase was
      observed in the treatment group. [18F]FDG SUVmean was significantly different in
      the treatment group compared to the control group (P = 0.0023) at Day 10. Within
      treatment groups [18F]FDG uptake and to a lesser extent [18F]FLT uptake at Day 3
      were significantly correlated with tumor growth at Day 10. CONCLUSIONS: [18F]FDG
      uptake early following treatment initiation predicted tumor sizes at Day 10,
      suggesting that [18F]FDG may be a valuable biomarker for non-invasive assessment
      of anti-tumor activity of belinostat.

PMID- 23548102
TI  - Liver stiffness is associated with monocyte activation in HIV-infected Ugandans
      without viral hepatitis.
AB  - A high prevalence of liver stiffness, as determined by elevated transient
      elastography liver stiffness measurement, was previously found in a cohort of HIV
      infected Ugandans in the absence of chronic viral hepatitis. Given the role of
      immune activation and microbial translocation in models of liver disease, a
      shared immune mechanism was hypothesized in the same cohort without other overt
      causes of liver disease. This study examined whether HIV-related liver stiffness
      was associated with markers of immune activation or microbial translocation (MT).
      A retrospective case-control study of subjects with evidence of liver stiffness
      as defined by a transient elastography stiffness measurement >=9.3 kPa
      (cases=133) and normal controls (n=133) from Rakai, Uganda was performed. Cases
      were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly
      active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin
      IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels
      were measured. Conditional logistic regression was used to estimate adjusted
      matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels
      were associated with a 19% increased odds of liver stiffness (adjMOR=1.19,
      p=0.002). In HIV-infected individuals, higher sCD14 levels were associated with a
      54% increased odds of having liver stiffness (adjMOR=1.54, p<0.001); however, the
      opposite was observed in HIV-negative individuals (adjMOR=0.57, p=0.001). No
      other biomarker was significantly associated with liver stiffness, and only one
      subject was found to have detectable LPS. Liver stiffness in HIV-infected
      Ugandans is associated with increased sCD14 indicative of monocyte activation in
      the absence of viral hepatitis or microbial translocation, and suggests that HIV
      may be directly involved in liver disease.

PMID- 23548103
TI  - Wintertime factors affecting contaminant distribution in a swine farrowing room.
AB  - An estimated 200,000 to 500,000 U.S. workers in concentrated animal feeding
      operations (CAFOs) are at risk of adverse respiratory outcomes from exposures to
      indoor contaminants. In the wintertime, general ventilation is minimized in the
      Midwest due to high heating costs required to maintain indoor temperatures
      optimal for animal production. Pit fans typically operate to exhaust under-floor
      manure pits, but little other fresh air intake exists. Many operators believe
      that these systems are sufficient to reduce contaminant concentrations within the
      building during winter. Investigating whether these pit fans provide sufficient
      protection against classic CAFO contaminants during minimal wintertime
      ventilation was warranted. Direct-reading instruments were used to measure and
      record concentrations of multiple contaminants using both fixed-area and mobile
      contaminant mapping in a farrowing room during a Midwest winter. With the
      exception of CO, concentrations were significantly (p<0.001) higher with the pit
      fan off compared with those with the pit fan on. Additional analyses identified
      that significant changes (p<0.001) in mean room concentrations of respirable dust
      (decreased, 77% with pit fan off and 87% with pit fan on) and CO2 (increased,
      24%) over the 5-hr study periods and that multiple fixed-area monitors rather
      than the much-used, single center-of-room monitor provided a more conservative
      (e.g., protective) assessment of room concentrations. While concentrations did
      not exceed occupational exposure limits from OSHA or ACGIH for individual
      contaminants, recommended agricultural health limits from exposure-response
      studies suggested in the literature were exceeded for respirable dust, CO2, and
      NH3, indicating a need to consider personal exposures and control options to
      reduce contaminant concentrations in farrowing rooms. Pit fans reduced NH3 and
      H2S concentrations, but these fans may not be sufficient to control dust and
      eliminate the need for secondary exposure prevention methods.

PMID- 23548104
TI  - Synthesis of a new conjugated polymer for DNA alkylation and gene regulation.
AB  - A new polyfluorene derivative containing pendent alkylating chlorambucil (PFP
      Cbl) was synthesized and characterized. Under direct incubation with DNA in
      vitro, PFP-Cbl could undergo an efficient DNA alkylating reaction and induce DNA
      cross-linking. In vitro transcription and translation experiment exhibited that
      the PFP-Cbl significantly down-regulated the gene expression of luciferase
      reporter plasmid. The down-regulation of gene expression was also verified
      through the transfection experiment of p-EGFP plasmid, which showed decreased
      green fluorescent protein (GFP) in cells. Meanwhile, the self-luminous property
      of PFP-Cbl could make it able to trace the internalized PFP-Cbl and plasmid
      complexes resulted from cross-linking in cells by fluorescent microscopy.
      Combining the features of alkylating function, multivalent binding sites, and
      fluorescent characteristics, PFP-Cbl provides a new insight in the area of gene
      regulation and extends the new applications of conjugated polymers (CPs).

PMID- 23548105
TI  - Could the Sasang constitution itself be a risk factor of abdominal obesity?
AB  - BACKGROUND: Abdominal obesity (AO) is a medical condition in which excess body
      fat accumulates in the abdomen. It may cause adverse effects on health and result
      in reduced life expectancy or increased health problems. While various genetic
      approaches have explained the risks of AO in Western society, the Sasang
      constitution (SC) has been identified as a risk factor in Korean medicine.
      Different SC types are associated with different fat distribution, body shapes
      and susceptibility to diseases. We evaluated whether the SC type could be a risk
      for AO in a cross-sectional study among Koreans. METHODS: In total, 2,528
      subjects aged over 30 years were recruited from 23 medical clinics. We collected
      waist circumference (WC), weight, height, and some clinical information for AO
      from the subjects. A Chi-square test and a one-way ANOVA were performed according
      to SC type (p < .05), while multiple logistic regression was used to produce odds
      ratios (ORs). RESULTS: The rates of AO in Tae-eumin (TE), Soeumin (SE), and
      Soyangin (SY) types were 63.7%, 14.7%, and 32.8% in males and 84.8%, 41.7%, and
      52.8% in females, respectively. The TE type was associated with increased AO
      prevalence compared with the SE and SY types in males (OR 1.79; 95% CI 1.02-3.15,
      p = 0.044 and OR 1.74; 95% CI 1.18-2.58, p = 0.006, respectively) and females (OR
      1.51; 95% CI 1.03-2.23, p = 0.037 and OR 1.88; 95% CI 1.32-2.68, p < 0.001,
      respectively) after adjusting for age, BMI, hypertension, diabetes mellitus,
      hypertriglyceridemia, and low HDL cholesterol. CONCLUSIONS: This study suggested
      that SC, particularly the TE type, might be significantly and independently
      associated with AO and could be considered a risk factor in predicting AO.

PMID- 23548106
TI  - Detection and whole genome sequence analysis of an enterovirus 68 cluster.
AB  - BACKGROUND: Enteroviruses are a common cause of human disease and are associated
      with a wide range of clinical manifestations. Enterovirus 68 is rarely detected
      yet was reported in many countries in 2010. Here enterovirus 68 was identified
      for the first time in New Zealand in 2010 and was detected in a further fourteen
      specimens over a six month period. OBJECTIVES: To genetically characterise
      enterovirus 68 specimens identified in New Zealand in 2010. STUDY DESIGN: The
      genome sequence of a New Zealand representative enterovirus 68 isolate was
      obtained. Ten clinical specimens were analysed by sequencing the VP1 region of
      the enterovirus 68 genome. RESULTS: Based on sequence analysis of the VP1 region
      and the full genome of one representative isolate, the New Zealand enterovirus 68
      isolates clustered with contemporary enterovirus 68 viruses and do not show any
      clear distinguishing genetic diversity when compared to other strains. All
      fifteen specimens showed high similarity with enterovirus 68 by VP1 sequencing.
      The majority of New Zealand patients suffered from bronchiolitis, were less than
      two years of age and were of Pacific Island or Maori descent. CONCLUSIONS: We
      document the rare occurrence of an enterovirus 68 cluster in New Zealand in 2010.
      These viruses shared similarity with other clusters of enterovirus 68 that
      occurred globally in 2010. A greater awareness in enterovirus 68 infection may
      help detect this virus with increased frequency and enable us to better
      understand the role this strain plays in disease and the reasons behind this
      global emergence in 2010.

PMID- 23548107
TI  - Contrast mimicking a subarachnoid hemorrhage after lumbar percutaneous epidural
      neuroplasty: a case report.
AB  - INTRODUCTION: Subarachnoid hemorrhage is one of the most feared acute neurologic
      events. Accurate diagnosis of subarachnoid hemorrhage is essential, and computed
      tomography of the brain is the first diagnostic imaging study. However, in rare
      circumstances, a similar appearance may occur in the absence of blood in the
      subarachnoid space. The contrast enhancement of subarachnoid space is a rare
      complication after lumbar percutaneous epidural neuroplasty, with, to the best of
      our knowledge, no previous report in the literature. CASE PRESENTATION: A 42-year
      old Korean male patient, who underwent a spinal operation five years previously
      at the level of L4 to S1, visited our clinic with persistent and aggravating low
      back pain. An imaging study revealed the focal and diffuse disc protrusion at the
      level of L4/5 and L5/S1. The clinician decided to perform a lumbar percutaneous
      epidural neuroplasty. During the procedure, dural adhesion was suspected at the
      previously operated level, and the neuroplasty catheter was malpositioned into
      the intradural space on the first attempt. After the catheter was repositioned,
      the scheduled epidural neuroplasty was completed. Our patient had no definite
      abnormal neurological signs. But, after a day, our patient complained of severe
      headache with sustained high blood pressure without neurological disorientation.
      Computed tomography of his brain showed a subarachnoid hemorrhage-like appearance
      with intracranial air. Sequential angiography, subtractional magnetic resonance
      imaging and examination of the cerebrospinal fluid revealed no abnormalities.
      Follow-up computed tomography after one day revealed no definite intracranial
      hemorrhage, and our patient was discharged with improved low back pain without
      neurological deficit. CONCLUSION: We report a rare case of contrast mimicking a
      subarachnoid hemorrhage after lumbar percutaneous epidural neuroplasty. The
      physician should keep in mind a rare case like this, and the supine position with
      head elevation is necessary to avoid a similar complication after lumbar
      percutaneous epidural neuroplasty.

PMID- 23548108
TI  - Source tracking of human leptospirosis: serotyping and genotyping of Leptospira
      isolated from rodents in the epidemic area of Guizhou province, China.
AB  - BACKGROUND: Sustained human leptospirosis as well as death cases has been
      reported in Qiandongnan Prefecture, Southeast of Guizhou, China, recently, but
      these human patients were only clinically diagnosed, and leptospires have never
      been isolated from patients in these epidemic regions, In order to track the
      source of infection and understand the etiologic characteristic of leptospirosis,
      we performed rodent carrier surveillance for leptospirosis in the epidemic area
      in 2011. The population distribution of rodents in the epidemic regions was
      revealed. RESULTS: Four strains of leptospire were isolated from Apodemus
      agrarius. Microscopic agglutination test (MAT) confirmed the four isolates
      belonged to leptospiral serogroup Icterohaemorrhagiae. Multilocus sequence typing
      (MLST) indicated that all the four strains were defined as sequence type 1(ST1),
      which is identical to the three strains isolated from Rattus tanezumi in
      Rongjiang County in 2007. Clustering analysis of the MLST data indicated that the
      local isolates exactly matched with reference strain of leptospiral serovar Lai
      strain 56601, which is consistent with anti-Leptospira antibody detection of
      patients using MAT. CONCLUSIONS: Apodemus agrarius may be the potentially
      important carrier of leptospirosis and the potential source of leptospiral
      infection in human, and serovar Lai maybe the epidemic serovar of Leptospira in
      the localities.

PMID- 23548109
TI  - Layer-by-layer thinning of MoS2 by plasma.
AB  - The electronic structures of two-dimensional materials are strongly dependent on
      their thicknesses; for example, there is an indirect to direct band gap
      transition from multilayer to single-layer MoS2. A simple, efficient, and
      nondestructive way to control the thickness of MoS2 is highly desirable for the
      study of thickness-dependent properties as well as for applications. Here, we
      present layer-by-layer thinning of MoS2 nanosheets down to monolayer by using
      Ar(+) plasma. Atomic force microscopy, high-resolution transmission electron
      microscopy, optical contrast, Raman, and photoluminescence spectra suggest that
      the top layer MoS2 is totally removed by plasma while the bottom layer remains
      almost unaffected. The evolution of Raman and photoluminescence spectra of MoS2
      with thickness change is also investigated. Finally, we demonstrate that this
      method can be used to prepare two-dimensional heterostructures with periodical
      single-layer and bilayer MoS2. The plasma thinning of MoS2 is very reliable (with
      almost 100% success rate), can be easily scaled up, and is compatible with
      standard semiconductor process to generate heterostructures/patterns at nanometer
      scale, which may bring out interesting properties and new physics.

PMID- 23548110
TI  - Nocardia veterana endogenous endophthalmitis in a cardiac transplant patient.
AB  - BACKGROUND: Endogenous endophthalmitis secondary to Nocardia species is extremely
      rare but often portends a poor visual prognosis often owing to the advanced
      nature of disease at presentation and delay in diagnosis. Patients who are
      systemically immunosuppressed are at greatest risk and early suspicion of the
      role of this organism in patients with acute panuveitis is paramount. FINDINGS: A
      66-year-old cardiac transplant patient on oral prednisone, Myfortic, and
      tacrolimus developed unilateral panuveitis with a focal white subretinal and
      retinal lesion. His past medical history was notable for Aspergillus pneumonia
      and cytomegalovirus retinitis in the contralateral eye 12 months prior. Aqueous
      humor sampling for eubacterial, eufungal, and viral PCR testing, as well as
      vitreous cultures for bacteria and fungi were unsuccessful in the identification
      of a causative organism. Progressive enlargement of the lesion was noted despite
      intravitreal foscarnet, vancomycin, ceftazidime, and voriconazole. A pars plana
      vitrectomy and retinal and subretinal biopsy led to the identification of
      Nocardia veterana, a recently identified Nocardia species. A combination of
      linezolid, meropenem, azithromycin, ceftriaxone, and intravitreal amikacin
      resulted in eradication of the infection. CONCLUSION: This is the first reported
      case of N. veterana endogenous endophthalmitis in an immunosuppressed patient.
      Pars plana vitrectomy with a subretinal biopsy was required to establish a
      diagnosis, as other testing including aqueous PCR and vitreous cultures were
      negative. The poor visual outcome in our patient highlights the importance of
      early consideration of Nocardia in the differential diagnosis of panuveitis with
      subretinal disease in the context of immunosuppression.

PMID- 23548111
TI  - Trunk and neck kinematics during overground manual wheelchair propulsion in
      persons with tetraplegia.
AB  - PURPOSE: To test the hypothesis that movement of the head and trunk increases as
      a consequence of speed during manual wheelchair propulsion over the ground in
      individuals with tetraplegia. METHODS: Seven adult participants with tetraplegia
      who used manual wheelchairs (5 men and 2 women, aged 33.0 +/- 10.2) were selected
      for the study. Participants propelled over the ground at three different speeds
      while video motion capture methods collected kinematic data. Variables
      investigated were forward flexion, lateral flexion and axial rotation for both
      the head and trunk. Repeated measures ANOVA were used to determine effects of
      speed on head and trunk movements. RESULTS: Both neck and trunk forward flexion
      significantly increased as a result of speed (p = 0.034, p = 0.031), with a large
      effect size (r = 0.6, r = 0.6) between slow and fast speeds. Lateral flexion and
      axial rotation were minimal for the neck and trunk and did not significantly
      increase with speed. CONCLUSIONS: Results suggest that manual wheelchair users
      with tetraplegia compensate for trunk muscle weakness by flexing the upper trunk
      and neck forward during manual wheelchair propulsion and that these movements
      increase with speed. Further studies should examine if these movements relate to
      overuse injuries and interventions that focus on improving manual wheelchair
      biomechanics of individuals with tetraplegia. IMPLICATIONS FOR REHABILITATION:
      Individuals who use manual wheelchairs utilize their upper extremities almost
      exclusively for both everyday mobility and participation in daily life activities
      which can often lead to overuse injuries and pain. Despite having a lack of trunk
      muscle innervation, manual wheelchair users with tetraplegia are able to
      compensate for this weakness by using the upper trunk and neck. The way in which
      force is translated from the trunk through the upper extremities to the pushrim
      may impact propulsion biomechanics, and ultimately the extent in which upper
      extremity pain and injury develops. A better understanding of how individuals
      with trunk impairments propel a manual wheelchair will help clinicians determine
      optimal wheelchair positioning and training during rehabilitation for individuals
      with tetraplegia. Clinicians can determine ways in which they can support manual
      wheelchair users to allow for most efficient biomechanics.

PMID- 23548112
TI  - Life cycle greenhouse gas emissions and freshwater consumption of Marcellus shale
      gas.
AB  - We present results of a life cycle assessment (LCA) of Marcellus shale gas used
      for power generation. The analysis employs the most extensive data set of any LCA
      of shale gas to date, encompassing data from actual gas production and power
      generation operations. Results indicate that a typical Marcellus gas life cycle
      yields 466 kg CO2eq/MWh (80% confidence interval: 450-567 kg CO2eq/MWh) of
      greenhouse gas (GHG) emissions and 224 gal/MWh (80% CI: 185-305 gal/MWh) of
      freshwater consumption. Operations associated with hydraulic fracturing
      constitute only 1.2% of the life cycle GHG emissions, and 6.2% of the life cycle
      freshwater consumption. These results are influenced most strongly by the
      estimated ultimate recovery (EUR) of the well and the power plant efficiency:
      increase in either quantity will reduce both life cycle freshwater consumption
      and GHG emissions relative to power generated at the plant. We conclude by
      comparing the life cycle impacts of Marcellus gas and U.S. coal: The carbon
      footprint of Marcellus gas is 53% (80% CI: 44-61%) lower than coal, and its
      freshwater consumption is about 50% of coal. We conclude that substantial GHG
      reductions and freshwater savings may result from the replacement of coal-fired
      power generation with gas-fired power generation.

PMID- 23548114
TI  - Speech disturbances due to left precentral cortical lesions.
AB  - We encountered two patients with lesions predominantly localized to the left
      precentral cortex who presented with speech disorders. Patient 1 had a lesion
      localized to the anterior part of the left precentral cortex along the precentral
      sulcus, in the middle part of the convexity. Patient 1 predominantly exhibited
      disturbance of prosody. Patient 2 had a lesion localized to the left precentral
      cortex, located slightly more posterior and more inferior in the convexity.
      Patient 2 predominantly exhibited disturbance of articulation, with distortion of
      sounds without apparent inconsistency. Even lesions localized to the left
      precentral cortex present with various types of speech disturbance. 

PMID- 23548113
TI  - Low birth weight in newborns to women employed in jobs with frequent exposure to
      organic solvents.
AB  - The effects of occupational exposure to organic solvents in pregnancy on foetal
      growth are still unclear. Our aim was to study whether live newborns to women
      employed in paid jobs with frequent exposure had a different risk of being born
      with low birth weight (LBW), compared to those of women in jobs without such
      exposure. The study population was all singleton newborns delivered in the
      industrial township of Moncegorsk (N = 26,415). Information about occupation and
      characteristics of the mothers and babies was obtained from the local population
      based birth register, and registered job function was used to classify exposure.
      We observed an elevated risk of LBW among live, singleton newborns in the exposed
      group (adjusted odds ratio: 1.68 [95% CI: 1.18-2.41]), which predominantly
      consisted of painters. The adjusted odds of LBW in the exposed group were also
      higher among term-born neonates. In addition, a lower mean birth weight was
      observed among the exposed. 

PMID- 23548115
TI  - TV parenting practices: is the same scale appropriate for parents of children of
      different ages?
AB  - PURPOSES: Use multidimensional polytomous item response modeling (MPIRM) to
      evaluate the psychometric properties of a television (TV) parenting practices
      (PP) instrument. Perform differential item functioning (DIF) analysis to test
      whether item parameter estimates differed across education, language, or age
      groups. METHODS: Secondary analyses of data from three studies that included 358
      children between the ages of 3 and 12 years old in Houston, Texas. TV PP included
      15 items with three subscales: social co-viewing, instructive parental mediation,
      and restrictive parenting. The multidimensional partial credit model was used to
      assess the performance. DIF was used to investigate the differences in
      psychometric properties across subgroups. RESULTS: Classical test theory analyses
      revealed acceptable internal consistency reliability (Cronbach's alpha: 0.72 to
      0.83). More items displaying significant DIF were found across children's age
      groups than parental education or language groups. A Wright map revealed that
      items covered only a restricted range of the distribution, at the easier to
      respond end of the trait. CONCLUSIONS: TV PP scales functioned differently on the
      basis of parental education, parental language, and child age, with the highest
      DIF among the latter. Additional research is needed to modify the scales to
      minimize these moderating influences. Some items may be age specific.

PMID- 23548116
TI  - Quality and risk of bias in Panax ginseng randomized controlled trials: a review.
AB  - Panax ginseng is one of the most frequently used herbs in the world. Numerous
      trials have evaluated its clinical benefits. However, the quality of these
      studies has not been comprehensively and systematically assessed. We reviewed
      randomized controlled trials (RCTs) of Panax ginseng to evaluate their quality
      and risk of bias. We searched four English databases, without publication date
      restriction. Two reviewers extracted details about the studies' methodological
      quality, guided by the Consolidated Standards of Reporting Trials (CONSORT)
      checklist and its extension for herbal interventions. Risk of bias was determined
      using the Cochrane Risk of Bias tool. Of 475 potentially relevant studies, 58 met
      our inclusion criteria. In these 58 studies, 48.3% of the suggested CONSORT
      checklist items and 35.9% of the extended herbal items were reported. The quality
      of RCTs published after the CONSORT checklist improved. Until 1995 (before
      CONSORT) (n = 4), 32.8% of the items were reported in studies. From 1996-2006
      (CONSORT published and revised) (n = 30), 46.1% were reported, and from 2007 (n =
      24), 53.5% were reported (p = 0.005). After the CONSORT extension for herbal
      interventions was published in 2006, RCT quality also improved, although not
      significantly. Until 2005 (n = 34), 35.2% of the extended herbal items were
      reported in studies; and from 2006 onwards (n = 24), 37.3% were reported (p =
      0.64). Most studies classified risk of bias as "unclear". Overall, the quality of
      Panax ginseng RCT methodology has improved since the CONSORT checklist was
      introduced. However, more can be done to improve the methodological quality of,
      and reporting in, RCTs.

PMID- 23548117
TI  - Phlegm-dampness constitution: genomics, susceptibility, adjustment and treatment
      with traditional Chinese medicine.
AB  - The constitution of traditional Chinese medicine was established in 1970s by
      Chinese scholars, in which the constitutions of Chinese people were classified
      into nine types for study. The phlegm-dampness constitution is one of the nine
      constitutions and is the most common type in constitution study. Genomics studies
      found four upregulated genes: COPS8, GNPDA1, CD52 and ARPC3; and six
      downregulated genes: GSPT2, CACNB2, FLJ20584, UXS1, IL21R and TNPO in the phlegm
      dampness constitution. Gene functional analyses on genes affecting the
      differences between the phlegm-dampness constitution and the balanced
      constitution indicated that people with phlegm-dampness constitution were
      susceptible to hyperlipemia and diabetes. Results of epidemiological surveys also
      revealed that people with phlegm-dampness constitution have a much higher risk of
      obesity, metabolic syndrome, hypertension and diabetes than people with a
      balanced constitution. Therefore, differentiation of phlegm-dampness constitution
      could be performed in the normal population with the Constitution of Chinese
      Medicine Scale to estimate the risks of those diseases for prediction. For people
      with phlegm-dampness constitution, Chinese medicine could be used to reduce risk
      of related diseases. Constitution-based strategies in disease prevention and
      treatment are consistent with the current proposed 4P medical mode (personalized,
      predictive, preventive and participatory). With the rising burden of global
      disease and increasing medical expenditure, the objectives of medicine are
      transforming from treatment to prevention. Thus, studies on the phlegm-dampness
      constitution of traditional Chinese medicine are significantly important for the
      prediction and prevention of related diseases and maintenance of human health.

PMID- 23548118
TI  - The new use of an ancient remedy: a double-blinded randomized study on the
      treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is the most common chronic inflammatory disease with
      unknown causes and unknown cures in Western medicine. This double-blinded study
      aimed to investigate the efficacy and safety of a widely used traditional Chinese
      medicine (Paeoniflorin (PAE) plus cervus and cucumis polypeptide injection (CCPI)
      using disease-modifying antirheumatic drugs (DMARD) as a control (methotrexate
      (MTX) plus leflunomide (LEF)). Patients were randomly assigned to one of the
      three groups: PAE + CCPI, MTX + LEF, and MTX + LEF + CCPI. The primary end point
      was the American College of Rheumatology 20% improvement response criteria
      (ACR20). The secondary end point was that of adverse effect frequencies and the
      speed of onset action. Our results showed that more patients in the CCPI
      containing groups responded to the ACR20 during early treatment. After six
      months, ACR20 showed no significant difference among the three treatments. The
      maximum improvement in the two DMARD groups was significantly higher than that in
      the PAE + CCPI group (p < 0.01). CCPI made the onset action of the DMARD therapy
      4.6 times faster. PAE + CCPI had significantly lower adverse event incidences
      than the two DMARD groups. These results indicate that PAE + CCPI appear to be a
      more acceptable alternative to DMARDs when patients cannot use DMARDs. CCPI
      appears to be a beneficial add-on to DMARDs that makes the onset of action
      faster, especially when patients need to relieve RA symptoms as soon as possible.
      Although not as effective as DMARDs, PAE appears to be a safer option to
      substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue.

PMID- 23548119
TI  - The prevalence and determinants of Chinese medicine use by Australian women:
      analysis of a cohort of 10,287 women aged 56-61 years.
AB  - This study aimed to examine the factors associated with Chinese medicine use
      amongst a sample of 10,287 Australian women aged 56-61 years. Data was obtained
      from a cross-sectional postal questionnaire conducted in 2007, this being the
      fifth survey of the Australian Longitudinal Study on Women's Health. This
      representative sample of 10,287 women was randomly selected from the Health
      Insurance Commission (Medicare) database. The outcome measure was the use of
      Chinese medicine in the previous 12 months. The predictive factors included
      demographics, health status measures and health service utilization measures.
      Statistical analyses included univariate chi-square and ANOVA tests and backward
      stepwise multiple logistic regression modelling. The use of Chinese medicine
      amongst women aged 56-61 years appears to be strongly influenced by their country
      of birth, consultation with a range of CAM practitioners, and the use of some
      self-prescribed CAM. Interestingly, severe tiredness was the only symptom or
      diagnosis that predicted Chinese medicine use. Given the substantial prevalence
      of Chinese medicine use and the finding that the use of Chinese medicine is
      heavily integrated alongside the use of many other CAM and conventional
      treatments, it is imperative for the safety of patients that health professionals
      (across complementary and conventional healthcare) fully recognise the possible
      Chinese medicine use amongst their practice populations. In order to help inform
      relevant practice and policy development it is also important that future
      research further examining women's decision-making, motivations and evaluations
      regarding Chinese medicine use considers such issues within the context of
      broader CAM and conventional health care utilization.

PMID- 23548120
TI  - Amniotic pocket changes following Wu-Ling-San treatment for gestational edema.
AB  - To determine whether the maternal administration of Wu-Ling-San during pregnancy
      affects amniotic fluid volume, we measured the fluid levels in pregnant women who
      either had or hadn't been administrated Wu-Ling-San. We investigated 504 amniotic
      pocket (AP) measurements in 61 healthy pregnant women, 437 AP measurements in 71
      untreated pregnant women who exhibited pretibial edema during pregnancy, and 82
      AP measurements in 21 pregnant women who exhibited pretibial edema during
      pregnancy and were treated with Wu-Ling-San therapy (Goreisan, 7.5 g/day). Among
      the 3 groups, differences in AP were not observed prior to 35 weeks of gestation.
      After 36 weeks of gestation, AP measures were significantly higher in the Wu-Ling
      San-treated group (3.78 +/- 0.81 cm), compared to the untreated group (3.34 +/-
      0.79 cm) (p = 0.0036). We identified no significant AP differences between the Wu
      Ling-San-treated and control groups. Our findings indicate that the
      administration of Wu-Ling-San to pregnant women with pretibial edema can prevent
      subsequent reductions in amniotic fluid volume. Thus, Wu-Ling-San may be helpful
      in the treatment of oligoamnios.

PMID- 23548121
TI  - The influence of electro-acupuncture stimulation to female constipation patients.
AB  - This study aims to examine electro-acupuncture stimulation (EA) assisted therapy
      with analysis of heart rate variability to understand autonomic nervous activity
      variability (ANAV) and to track the changes in female patients with constipation.
      The average ages were 42 +/- 12 years old. The participants were divided by a
      single-blind and randomized trial into two groups: the electro-acupuncture-point
      group, and the non-electro-acupuncture-point group. Both of the groups had eight
      treatments, once a week. For the electro-acupuncture (EA) group, needles were
      inserted into their Zusunli (ST36), Shangiuxu (ST37), Tiensu (ST25), Shueidao
      (ST28), Guanyuan (CV4) and Qihai (CV6) points. For the sham electro-acupuncture
      (SA) group, needles were inserted into acu-points that were not the ones
      mentioned for the EA group. While inserting needles, needles were inserted
      lightly into the participants' skin and removed quickly (mock Transcutaneous
      Electrical Nerve Stimulation, TENTS). After an eight-week treatment period, the
      autonomic nervous system activities of the SA group did not show significant
      differences in their heart rate variability. However, the autonomic nervous
      system activities of the EA group had continuously increased after each session.
      The normalized high frequency powers (nHFP) of their autonomic nervous system
      activities were 26.79 in the first week, and they increased to 32.28 in the
      fourth week. In the eighth week, their nHFP had increased to 37.60 (p < 0.05).
      The normalized low frequency power (nLFP) was 30.81 in the first week. However,
      it decreased to 25.98 after three weeks of treatment. After the eight-week
      treatment period, the nLFP decreased to 24.84 (p < 0.05). After the eight-week
      treatment, the control group did not appear to undergo any physiological change,
      while the constipation had been improved for the experimental group. It was found
      that the activation of parasympathetic nervous system in the experimental group
      increased after the eight-week treatment. The effects of such a result on the
      enhancement of the activation of parasympathetic nervous system and the
      improvement of constipation should be further discussed.

PMID- 23548122
TI  - Baicalein preconditioning protects cardiomyocytes from ischemia-reperfusion
      injury via mitochondrial oxidant signaling.
AB  - Previous studies suggest baicalein, in addition to its antioxidant effects,
      protects against hypoxia/reoxygenation injury via its pro-oxidant properties. We
      hypothesize that a brief period of baicalein treatment prior to
      ischemia/reperfusion (I/R) may trigger preconditioning protection via a
      mitochondrial pro-oxidant mechanism. Using an established chick cardiomyocyte
      model of I/R, cells were preconditioned with baicalein (10 MUM) for 10 min
      followed by 10-min wash prior to I/R. Intracellular oxidants were measured using
      2', 7'-dichlorofluorescin diacetate (DCFH/DA). Cell viability was assessed by
      propidium iodide and apoptosis determined by DNA fragmentation. Baicalein induced
      a transient but significant increase of DCF fluorescence within the 10-min
      preconditioning period, and led to significant reduction of cell death (38.9 +/-
      1.8% vs. 58.7 +/- 1.2% in I/R control, n = 6, p < 0.001) and DNA fragmentation
      after I/R. Cotreatment with N-acetylcysteine (500 MUM), mitochondrial complex III
      electron transport chain inhibitor myxothiazol (1 MUM), mitochondrial KATP
      channel blocker 5-hydroxydecanoate-Na (5-HD, 500 MUM) or anion channel inhibitor
      4', 4'-diisothiocyanato-stilbene-2, 2'-disulfonic acid (DIDS, 200 MUM) resulted
      in significant abrogation of oxidant increase during induction as well as the
      protection conferred by baicalein preconditioning. These results suggest that
      baicalein preconditioning exhibits significant anti-apoptotic protection against
      cardiomyocyte I/R injury by mitochondrial oxidant signaling, which was in part
      mediated by mitochondrial KATP channel and anion channel opening.

PMID- 23548123
TI  - Effects of zishentongluo in patients with early-stage diabetic nephropathy.
AB  - The purpose of this study was to assess the efficacy of zishentongluo (ZSTL) for
      the treatment of diabetic nephropathy (DN) and its related mechanisms. Forty-five
      patients with DN were randomized to receive either ZSTL (n = 25) or benazepril (n
      = 20), an angiotensin converting enzyme inhibitor, for 12 weeks. Conventional
      biochemical tests were performed to determine fasting blood glucose (FBG),
      glycated hemoglobin (HbA1c), serum creatinine (SCr), endogenous creatinine
      clearance rate (Ccr), total cholesterol (TC), and triglyceride (TG) levels. The
      urinary albumin excretion rate (UAER), and endothelin 1 (ET-1), and atrial
      natriuretic peptide (ANP) levels were determined with a radioimmunoassay, and
      vascular endothelial growth factor (VEGF) was detected using an enzyme-linked
      immunosorbent assay. The primary endpoint was change from the baseline to post
      treatment in HbA1c. Secondary endpoints were change from baseline to post
      treatment in FBG, TC, TG, UAER, SCr, Ccr, VI-C, ANP, ET-1, and VEGF. ZSTL was
      significantly more effective at improving the primary (i.e., HbA1c) and secondary
      (i.e., FBG, TC, TG, UAER, SCr, ANP, ET-1, and VEGF) outcomes than benazepril (p <
      0.05). These findings suggest that ZSTL is superior to benazepril at improving
      the metabolic and renal functioning in patients with early-stage DN, in part, by
      modifying ANP, ET-1, and VEGF.

PMID- 23548124
TI  - Preventive and therapeutic effects of ginsenoside Rb1 for neural injury during
      cerebral infarction in rats.
AB  - To examine the preventive and therapeutic effects of ginsenoside Rb1 for neural
      injury during cerebral infarction, we used a middle cerebral artery occlusion
      (MCAO) model in rats to investigate the effects of ginsenoside Rb1 with Edaravone
      as a control. Ginsenoside Rb1 was given to the rats by intragastric
      administration either before or after the MCAO surgery to study its preventive
      and therapeutic effects. Ginsenoside Rb1-treated rats had a smaller infarct
      volume than the positive control. Interleukin-1 (IL-1), brain-derived
      neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha),
      neurofilament (NF) and growth associated protein-43 (GAP-43) were measured to
      determine brain damage and the recovery of nerves. These findings suggest that
      ginsenoside Rb1 has neuroprotective effects in rats, and the protection
      efficiency is higher than Edaravone. The protective mechanism is different from
      Edaravone. The preventive ability of ginsenoside Rb1 is higher than its repair
      ability in neuroprotection in vivo.

PMID- 23548125
TI  - Polysaccharide from Fuzi likely protects against starvation-induced cytotoxicity
      in H9c2 cells by increasing autophagy through activation of the AMPK/mTOR
      pathway.
AB  - There is increasing evidence that starvation induces autophagy, which may be
      protective during starvation, in an AMPK-dependent manner. Polysaccharides from
      Fuzi (FPS) reportedly have protective effects on nutrition-limited livers. The
      present study was designed to determine whether FPS protected H9c2 cells against
      starvation-induced cytotoxicity using an AMPK/mTOR-dependent mechanism. H9c2
      cells were incubated in serum and glucose starvation media for 12 hours to
      establish a cell injury model. 3-Methyladenine (3MA, an autophagy inhibitor) was
      used to identify the exact role of autophagy in starvation. Cells were incubated
      with different FPS concentrations, and the cell injury levels, autophagy activity
      and AMPK/mTOR phosphorylation were measured. Adenine 9-beta-D-arabinofuranoside
      (Ara-A, an AMPK inhibitor) and 5-amino-4-imidazole-carboxamide riboside (AICAR,
      an AMPK activator) were used to identify whether the AMPK/mTOR pathway was
      involved in FPS-mediated cardioprotection. We demonstrated that starvation
      decreased cell viability in a time-dependent manner, and 3MA-induced autophagy
      inhibition aggravated the reduced cell viability. FPS treatment attenuated the
      cell viability decrement and the starvation-induced decline in the mitochondrial
      membrane potential (MMP), and autophagy; also, the AMPK/mTOR pathways were
      activated during treatment. Ara-A treatment abolished the protective effect of
      FPS, while AICAR treatment had a similar effect to FPS. We conclude that
      autophagy attenuates starvation-induced cardiomyocyte death, and FPS increases
      autophagy activity to protect against starvation-induced cytotoxicity in H9c2
      cells, likely through AMPK/mTOR pathway activation.

PMID- 23548126
TI  - Inhibition of monocarboxylate transporter-mediated absorption of valproic acid by
      Gegen-Qinlian-Tang.
AB  - Valproic acid (VPA), an anti-epileptic drug with a narrow therapeutic index, is a
      substrate of the monocarboxylate transporter (MCT). In this study, we
      investigated the effect of Gegen-Qinlian-Tang (GQT), a Chinese Medicine
      prescription containing Puerariae Radix (PR), Scutellariae Radix (SR), Coptidis
      Rhizoma (CR) and Glycyrrhizae Radix (GR), on the pharmacokinetics of VPA, as a
      probe drug of MCT, in rats and the underlying mechanism. Sprague-Dawley rats were
      orally administered VPA with and without GQT in crossover design. The serum
      concentrations of VPA were determined by a fluorescence polarization immunoassay.
      The results showed that coadministration with 2.0 and 4.0 g/kg of GQT remarkably
      decreased the Cmax of VPA by 72% and 74% and reduced the AUC 0-t by 63% and 53%,
      respectively. The mechanism study using Caco-2 cells revealed that the uptake
      function of MCT was inhibited by GQT and each component herb. In conclusion, the
      MCT-mediated absorption of VPA was significantly decreased by GQT and its
      component herbs.

PMID- 23548127
TI  - Bauhinia championii extraction treatment of collagen-induced arthritis via
      downregulation of the expression of TLR4, MyD88 and NF-kappaB.
AB  - Rheumatoid arthritis (RA) has emerged as an important worldwide public health
      problem. Due to the lack of efficacy and major side effects related to many
      Western medical treatments, traditional Chinese medicine or herbal medicine is
      very often used to treat this disease. In the present study, we evaluated the
      effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) in a rat model
      of RA induced by type-II collagen. Wistar rats with type-II collagen-induced
      arthritis (CIA) were given either 125 or 500 mg/kg of BCBE for RA. Paw swelling
      and weight were measured, and pathological joint sections of CIA rats were
      observed using the hematoxylin and eosin (HE) staining method. Protein and mRNA
      expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88
      (MyD88) and nuclear transcription factor kappaB (NF-kappaB) were determined by
      western blot analysis and reverse transcription-polymerase chain reaction (RT
      PCR) analysis in synovial tissue. During therapeutic treatment, BCBE
      significantly suppressed paw swelling, increased weight loss and ameliorated
      pathological joint changes. The protein and mRNA expressions of TLR4, MyD88 and
      NF-kappaB were downregulated in the CIA model when treated with BCBE. In
      conclusion, these results suggest that the treatment of RA with BCBE confers anti
      RA activity and has therapeutic potential in this CIA model.

PMID- 23548128
TI  - Protective effect of rosmarinic acid is through regulation of inflammatory
      cytokine in cadmium-induced ototoxicity.
AB  - Cadmium ( Cd(2+) ) is an environmental contaminant that causes a variety of
      adverse effects. Auditory cells are sensitive to cadmium, and the cochlea is more
      vulnerable to cadmium toxicity than the other parts of the auditory system.
      Rosmarinic acid (RA) exhibits a wide spectrum of biological activities, mainly
      antioxidant and anti-inflammatory activities. However, the regulatory effects of
      RA in the auditory system have not been elucidated. In this study, we
      investigated the protective effects of RA on Cd(2+) -induced ototoxicity in vitro
      and ex vivo. The findings showed that RA inhibited Cd(2+) -mediated cell
      toxicity, reactive oxygen species generation, interleukin (IL)-6 and IL-1beta
      production, the translocation of the apoptosis inducing factor into the nucleus
      and activation of caspases-3 in an auditory cell line, HEI-OC1. In addition, RA
      prevented the destruction of hair cell arrays in the rat organ of Cortiprimary
      explants in the presence of Cd(2+) . These results are expected to improve our
      understanding of the pharmacological mechanism of RA, and help develop potential
      therapeutic strategies against ototoxicity.

PMID- 23548129
TI  - Chemical characterization and in vivo anti-inflammatory activities of Actinidia
      callosa var. ephippioides via suppression of proinflammatory cytokines.
AB  - Actinidia callosa var. ephippioides (ACE) has been widely used to treat anti
      pyretic, antinociceptive, anti-inflammation, abdominal pain and fever in Taiwan.
      This study aims to determine the mechanism of anti-inflammatory activities of
      ethyl acetate fraction of ACE (EA-ACE) using a model of lambda-carrageenan (Carr)
      induced paw edema in mouse model. In HPLC analysis, chemical characterization of
      EA-ACE was established. In order to investigate the anti-inflammatory mechanism
      of EA-ACE, we have detected the activities of catalase (CAT), superoxide
      dismutase (SOD), and glutathione peroxidase (GPx) and the levels of
      malondialdehyde (MDA) in the paw edema. Serum NO, tumor necrosis factor alpha
      (TNF-alpha), and interleukin-1beta (IL-1beta) were evaluated. Chemical
      characterization from HPLC indicated that EA-ACE contains betulinic acid, ursolic
      acid and oleanolic acid. In the anti-inflammatory test, EA-ACE decreased the paw
      edema after Carr administration, increased the activities of CAT, SOD, and GPx
      and decreased the MDA level in the edema paw at the 5th hr after Carr injection.
      EA-ACE affects the serum NO, TNF-alpha, and IL-1beta levels at the 5th hr after
      Carr injection. EA-ACE decreased Carr-induced inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2) expressions by Western blotting. Actinidia
      callosa var. ephippioides have the potential to provide a therapeutic approach to
      inflammation-associated disorders.

PMID- 23548130
TI  - Curculigo orchioides protects cisplatin-induced cell damage.
AB  - Cisplatin is commonly used as a chemotherapeutic agent against many human
      cancers. However, it generates reactive oxygen species (ROS) and has serious dose
      limiting side effects, including ototoxicity. The roots of Curculigo orchioides
      (C. orchioides) have been used to treat auditory diseases such as tinnitus and
      hearing loss in Chinese traditional medicine. In the present study, we
      investigated the protective effects of an ethanol extract obtained from C.
      orchioides rhizome (COR) on cisplatin-induced cell damage in auditory cells (HEI
      OC1). COR (2.5-25 MUg/ml) inhibited cisplatin-induced HEI-OC1 cell damage in a
      dose-dependent manner. To investigate the protective mechanism of COR on
      cisplatin cytotoxicity in HEI-OC1 cells, we measured the effects of COR on ROS
      generation and lipid peroxidation in cisplatin-treated cells as well as its
      scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen
      peroxide, and DPPH radicals. COR (1-25 MUg/ml) had scavenging activities against
      superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals, as
      well as reduced lipid peroxidation. In in vivo experiments, COR was shown to
      reduce cochlear and peripheral auditory function impairments through cisplatin
      induced auditory damage in mice. These results indicate that COR protects from
      cisplatin-induced auditory damage by inhibiting lipid peroxidation and scavenging
      activities against free radicals.

PMID- 23548131
TI  - Preliminary evaluation of the interactions of Panax ginseng and Salvia
      miltiorrhiza Bunge with 5-fluorouracil on pharmacokinetics in rats and
      pharmacodynamics in human cells.
AB  - An increasing number of cancer patients are using herbs in combination with
      conventional chemotherapeutic treatment. It is therefore important to study the
      potential consequences of the interactions between herbs and anticancer drugs.
      The effects of extracts from Panax ginseng (PGS) and Salvia miltiorrhiza Bunge
      (SMB) on the pharmacokinetics of 5-fluorouracil (5-FU) were performed in vivo and
      detected by high performance liquid chromatography (HPLC), while, an ATP assay
      was used to study the pharmacodynamic interactions in vitro. The results of the
      pharmacokinetic experiments showed a significant increase in the elimination half
      life (t1/2(k e )) of 5-FU in the PGS-pretreated group and in the area under the
      curve (AUC) in the SMB-pretreated group compared with the control group. However,
      after SMB pretreatment, weight loss was observed in rats. The results of
      pharmacodynamic experiments showed that neither PGS nor SMB, when used alone,
      directly inhibited cancer cell growth at 0.1-100 MUg/ml. Moreover, PGS had a
      synergistic cytotoxic effect with 5-FU on human gastric cancer cells but not on
      normal gastric cells. The results imply that when combined with 5-FU, PGS may be
      a better candidate for further study. This study might provide insights for the
      selection of herbal-chemotherapy agent interactions.

PMID- 23548133
TI  - Systemic treatment for hereditary cancers: a 2012 update.
AB  - The history of specific therapy for hereditary tumors dates back to mid 1980s and
      involves a number of reports demonstrating regression of familial colon polyps
      upon administration of sulindac. Virtually no clinical studies on other
      hereditary cancer types were available until the year 2009, when Byrski et al.
      presented the data on unprecedented sensitivity of BRCA1-associated breast
      malignancies to cisplatin. This breakthrough has revived interest to the
      treatment of cancer in germ-line mutation carriers. Recent trials and clinical
      observations have confirmed the efficacy of platinating agents and PARP
      inhibitors in BRCA1/2-driven breast, ovarian and pancreatic carcinomas. Pegylated
      liposomal doxorubicin may be considered as a promising treatment option for
      BRCA1/2-related ovarian cancer after the failure of platinum-containing therapy.
      Several novel drugs have been recently introduced in the management of rare
      familial tumor syndromes. Vandetanib, a low-molecular weight RET kinase
      inhibitor, demonstrated substantial efficacy in the treatment of hereditary and
      sporadic medullary thyroid cancer. Vismodegib, an inhibitor of SMO oncoprotein,
      caused regression of basal-cell carcinomas in patients with Gorlin syndrome. Down
      regulation of mTOR kinase by everolimus has been successfully used for the
      therapy of subependymal giant-cell astrocytomas in patients with tuberous
      sclerosis. The achievements in the prevention, diagnostics and treatment of
      hereditary cancers may serve as an excellent example of triumph of translational
      medicine.

PMID- 23548132
TI  - High resolution melting analysis of KRAS, BRAF and PIK3CA in KRAS exon 2 wild
      type metastatic colorectal cancer.
AB  - BACKGROUND: KRAS is an EGFR effector in the RAS/RAF/ERK cascade that is mutated
      in about 40% of metastatic colorectal cancer (mCRC). Activating mutations in
      codons 12 and 13 of the KRAS gene are the only established negative predictors of
      response to anti-EGFR therapy and patients whose tumors harbor such mutations are
      not candidates for therapy. However, 40 to 60% of wild-type cases do not respond
      to anti-EGFR therapy, suggesting the involvement of other genes that act
      downstream of EGFR in the RAS-RAF-MAPK and PI3K-AKT pathways or activating KRAS
      mutations at other locations of the gene. METHODS: DNA was obtained from a
      consecutive series of 201 mCRC cases (FFPE tissue), wild-type for KRAS exon 2
      (codons 12 and 13). Mutational analysis of KRAS (exons 3 and 4), BRAF (exons 11
      and 15), and PIK3CA (exons 9 and 20) was performed by high resolution melting
      (HRM) and positive cases were then sequenced. RESULTS: One mutation was present
      in 23.4% (47/201) of the cases and 3.0% additional cases (6/201) had two
      concomitant mutations. A total of 53 cases showed 59 mutations, with the
      following distribution: 44.1% (26/59) in KRAS (13 in exon 3 and 13 in exon 4),
      18.6% (11/59) in BRAF (two in exon 11 and nine in exon 15) and 37.3% (22/59) in
      PIK3CA (16 in exon 9 and six in exon 20). In total, 26.4% (53/201) of the cases
      had at least one mutation and the remaining 73.6% (148/201) were wild-type for
      all regions studied. Five of the mutations we report, four in KRAS and one in
      BRAF, have not previously been described in CRC. BRAF and PIK3CA mutations were
      more frequent in the colon than in the sigmoid or rectum: 20.8% vs. 1.6% vs. 0.0%
      (P=0.000) for BRAF and 23.4% vs. 12.1% vs. 5.4% (P=0.011) for PIK3CA mutations.
      CONCLUSIONS: About one fourth of mCRC cases wild-type for KRAS codons 12 and 13
      present other mutations either in KRAS, BRAF, or PIK3CA, many of which may
      explain the lack of response to anti-EGFR therapy observed in a significant
      proportion of these patients.

PMID- 23548134
TI  - Methods for setting priorities in systematic reviews.

PMID- 23548135
TI  - Condition-specific measure was more responsive than generic measure in colorectal
      cancer: all but social domains.
AB  - OBJECTIVE: To examine the responsiveness of generic and condition-specific
      instruments based on the anchor of self-reported level of global change in
      patients with colorectal cancer (CRC). STUDY DESIGN AND SETTING: Three hundred
      thirty-three patients with CRC were surveyed at two assessments at baseline and
      follow-up at 6 months from September 2009 to July 2010 using the Short Form-12
      Health Survey version 2 (SF-12v2) and Functional Assessment of Cancer Therapy
      Colorectal (FACT-C) measures. The responsiveness of the two measures was
      evaluated using standardized effect size, standardized response mean,
      responsiveness statistic, and receiver operating characteristic (ROC) curve
      analysis. RESULTS: In worsened group, internal responsiveness of detecting
      negative changes was satisfactory for most subscales of FACT-C and SF-12v2. The
      FACT-C subscales were significantly more responsive to positive changes detection
      than the SF-12v2 subscales in improved group. Physical well-being subscale, Trial
      Outcome Index (TOI), and total score of FACT-C were more externally responsive to
      ROC curve analysis. The FACT-C measure was generally more responsive to changes
      in health status compared with SF-12v2 measure. CONCLUSION: TOI and total score
      of FACT-C were the most responsive among subscales of condition-specific measure,
      which were more responsive than all generic subscales with the exception of
      social domain. Complementary use of condition-specific and generic instruments to
      evaluate the health-related quality of life of CRC patients is encouraged.

PMID- 23548136
TI  - Intrathoracal cholecystitis calculosa in a right-sided posttraumatic
      diaphragmatic hernia: a case report.
AB  - INTRODUCTION: Injuries of the diaphragm were first described in 1541 by Sennertus
      and the initial repair was performed by Riolfi in 1886. Posttraumatic
      diaphragmatic hernia in adults is usually caused by blunt trauma and may remain
      asymptomatic and undiagnosed for many years. Right-sided tears are significantly
      less likely than left-sided tears because of the protective effect of the liver.
      They are associated with high mortality and morbidity. The rupture of the right
      side of the diaphragm and the presence of an inflamed gallbladder in the thoracic
      cavity are uncommon. CASE PRESENTATION: We present the case of a 57-year-old
      Albanian man with prolapses of his gallbladder and other abdominal organs into
      the thoracic cavity through the herniation of his right hemidiaphragm due to
      trauma. The diaphragmatic hernia and gallstones seen in the thorax computed
      tomography scan were diagnostic. The organs herniated to the thoracic cavity were
      placed back into the abdominal cavity, a cholecystectomy was performed and the
      defect in the diaphragm was repaired with a prolene mesh graft during the
      operation. The patient was discharged 10 days after the surgical procedure, and
      no complications were reported. CONCLUSION: Diaphragmatic hernia should be
      considered as a possible diagnosis in patients with respiratory disorders or
      unusual shadows in the thoracic region after recently sustained injury or with a
      history of injury. The prolapse of a gallbladder is rare. The symptoms are
      uncharacteristic and patients with this disease may remain without symptoms for a
      long period. Treatment is surgical.

PMID- 23548137
TI  - Consultations with complementary and alternative medicine practitioners by older
      Australians: results from a national survey.
AB  - BACKGROUND: The use of complementary and alternative medicines (CAM) and CAM
      practitioners is common, most frequently for the management of musculoskeletal
      conditions. Knowledge is limited about the use of CAM practitioners by older
      people, and specifically those with other long term or chronic conditions.
      METHODS: In 2011 we conducted an Australia wide survey targeting older adults
      aged over 50 years (n = 2540). Participants were asked to identify their chronic
      conditions, and from which health professionals they had 'received advice or
      treatment from in the last 3 months', including 'complementary health
      practitioners, e.g. naturopath'. Descriptive analyses were undertaken using SPSS
      and STATA software. RESULTS: Overall, 8.8% of respondents reported seeing a CAM
      practitioner in the past three months, 12.1% of women and 3.9% of men; the vast
      majority also consulting medical practitioners in the same period. Respondents
      were more likely to report consulting a CAM practitioner if they had
      musculoskeletal conditions (osteoporosis, arthritis), pain, or
      depression/anxiety. Respondents with diabetes, hypertension and asthma were least
      likely to report consulting a CAM practitioner. Those over 80 reported lower use
      of CAM practitioners than younger respondents. CAM practitioner use in a general
      older population was not associated with the number of chronic conditions
      reported, or with the socio-economic level of residence of the respondent.
      CONCLUSION: Substantial numbers of older Australians with chronic conditions seek
      advice from CAM practitioners, particularly those with pain related conditions,
      but less often with conditions where there are clear treatment guidelines using
      conventional medicine, such as with diabetes, hypertension and asthma. Given the
      policy emphasis on better coordination of care for people with chronic
      conditions, these findings point to the importance of communication and
      integration of health services and suggest that the concept of the 'treating
      team' needs a broad interpretation.

PMID- 23548138
TI  - Physico-chemical characterization of African urban aerosols (Bamako in Mali and
      Dakar in Senegal) and their toxic effects in human bronchial epithelial cells:
      description of a worrying situation.
AB  - BACKGROUND: The involvement of particulate matter (PM) in cardiorespiratory
      diseases is now established in developed countries whereas in developing areas
      such as Africa with a high level of specific pollution, PM pollution and its
      effects are poorly studied. Our objective was to characterize the biological
      reactivity of urban African aerosols on human bronchial epithelial cells in
      relation to PM physico-chemical properties to identify toxic sources. METHODS:
      Size-speciated aerosol chemical composition was analyzed in Bamako (BK, Mali, 2
      samples with one having desert dust event BK1) and Dakar (DK; Senegal) for
      Ultrafine UF, Fine F and Coarse C PM. PM reactivity was studied in human
      bronchial epithelial cells investigating six biomarkers (oxidative stress
      responsive genes and pro-inflammatory cytokines). RESULTS: PM mass concentrations
      were mainly distributed in coarse mode (60%) and were impressive in BK1 due to
      the desert dust event. BK2 and DK samples showed a high content of total carbon
      characteristic of urban areas. The DK sample had huge PAH quantities in bulk
      aerosol compared with BK that had more water soluble organic carbon and metals.
      Whatever the site, UF and F PM triggered the mRNA expression of the different
      biomarkers whereas coarse PM had little or no effect. The GM-CSF biomarker was
      the most discriminating and showed the strongest pro-inflammatory effect of BK2
      PM. The analysis of gene expression signature and of their correlation with main
      PM compounds revealed that PM-induced responses are mainly related to organic
      compounds. The toxicity of African aerosols is carried by the finest PM as with
      Parisian aerosols, but when considering PM mass concentrations, the African
      population is more highly exposed to toxic particulate pollution than French
      population. Regarding the prevailing sources in each site, aerosol biological
      impacts are higher for incomplete combustion sources resulting from two-wheel
      vehicles and domestic fires than from diesel vehicles (Dakar). Desert dust events
      seem to produce fewer biological impacts than anthropogenic sources. DISCUSSION:
      Our study shows that combustion sources contribute to the high toxicity of F and
      UF PM of African urban aerosols, and underlines the importance of emission
      mitigation and the imperative need to evaluate and to regulate particulate
      pollution in Africa.

PMID- 23548140
TI  - The aging tsunami: time for a new metaphor?

PMID- 23548141
TI  - Aging well and gay in rural America: a case study.
AB  - Using person-environment-fit theory as a theoretical framework, this qualitative
      case study examined, through in-depth interviews and thematic analysis, the lived
      experience of an older gay man who has lived solely in rural communities. An
      overarching theme of life satisfaction clearly emerged, along with themes
      regarding supportive social networks and disclosure management of his sexual
      orientation. The findings suggest that although it is important to understand the
      challenges faced by the lesbian, gay, bisexual, and transgender community in
      rural environments, it is equally important to shed light on the ways in which
      older adults age well within these communities.

PMID- 23548142
TI  - Addressing individual differences in mobility transition counseling with older
      adults.
AB  - In the final phase of a 3-phase project, the Assessment of Readiness for Mobility
      Transition (ARMT) was clinically validated, emphasizing assessment/intervention.
      ARMT and coping, health/vision status, and social support measures were
      administered to 133 community-dwelling older adults. Concurrent validity is
      supported. Higher readiness to cope with mobility transition and self-confidence
      related to fall risk, higher self-rated health/vision, and fewer maladaptive
      behaviors, but not social support/adaptive coping, suggesting that those at risk
      can benefit from person-centered intervention to mobilize strengths for
      transportation/mobility planning. Older drivers may harbor unrealistic
      expectations regarding nonfamily mobility support. Implications for practice,
      education, research, and policy are presented.

PMID- 23548143
TI  - Migration narratives: expanding methods to examine the interaction of person and
      environment among aging gay men.
AB  - As they age, gay and bisexual men are embedded in multiple environments and
      communities. This article reanalyzes data collected as part of a larger
      qualitative study of crystal methamphetamine use in New York City. Focusing on
      the migration narratives of 30 racially/ethnically diverse men, age 40 years old
      and older, recruited from multiple venues several key areas emerged:
      ostracization, lack of affirmation as well as movement activities. Interactively
      they transformed social practices and increased spaces to explore sexuality,
      build community engagements and exchange resources. This study suggests that
      assessment of gay men (and other marginalized groups) may be enhanced through
      application of migration narratives.

PMID- 23548139
TI  - Human single-stranded DNA binding proteins are essential for maintaining genomic
      stability.
AB  - The double-stranded conformation of cellular DNA is a central aspect of DNA
      stabilisation and protection. The helix preserves the genetic code against
      chemical and enzymatic degradation, metabolic activation, and formation of
      secondary structures. However, there are various instances where single-stranded
      DNA is exposed, such as during replication or transcription, in the synthesis of
      chromosome ends, and following DNA damage. In these instances, single-stranded
      DNA binding proteins are essential for the sequestration and processing of single
      stranded DNA. In order to bind single-stranded DNA, these proteins utilise a
      characteristic and evolutionary conserved single-stranded DNA-binding domain, the
      oligonucleotide/oligosaccharide-binding (OB)-fold. In the current review we
      discuss a subset of these proteins involved in the direct maintenance of genomic
      stability, an important cellular process in the conservation of cellular
      viability and prevention of malignant transformation. We discuss the central
      roles of single-stranded DNA binding proteins from the OB-fold domain family in
      DNA replication, the restart of stalled replication forks, DNA damage repair,
      cell cycle-checkpoint activation, and telomere maintenance.

PMID- 23548144
TI  - The couples life story approach: a dyadic intervention for dementia.
AB  - This article describes an approach for working with individuals who have
      dementia, along with their spouses or partners. The 5-week intervention focuses
      on helping couples communicate, reminisce about the story of their relationship,
      find photographs and mementoes from their past, and develop a book that
      incorporates these mementoes. This clinical approach highlights the strengths and
      the resilience of couples and adds to the limited repertoire of dyadic
      interventions for dementia care which are currently available. Preliminary
      findings from 24 couples are presented, including the intervention's feasibility
      and acceptability.

PMID- 23548145
TI  - The development of Korea's new long-term care service infrastructure and its
      results: focusing on the market-friendly policy used for expansion of the numbers
      of service providers and personal care workers.
AB  - One of the main reasons for reforming long-term care systems is a deficient
      existing service infrastructure for the elderly. This article provides an
      overview of why and how the Korean government expanded long-term care
      infrastructure through the introduction of a new compulsory insurance system,
      with a particular focus on the market-friendly policies used to expand the
      infrastructure. Then, the positive results of the expansion of the long-term care
      infrastructure and the challenges that have emerged are examined. Finally, it is
      argued that the Korean government should actively implement a range of practical
      policies and interventions within the new system.

PMID- 23548147
TI  - The Western lifestyle and its long way to sustainability.
AB  - Since Fukushima, few people still consider nuclear power as a safe technology.
      The explosion of Deepwater Horizon was yet another incident revealing the dangers
      involved in the hunt for fossil fuels. Despite the public attention and outrage
      at these events, neither the concept of environmental citizenship, nor the United
      Nations Framework Convention on Climate Change has prevailed in the struggle
      against environmental degradation. Economic growth offsets efficiency gains,
      while strategies for energy sufficiency are usually not seriously considered.
      Action toward a more sustainable society, for example, a 2000 W- and 1 ton CO2
      society, must be taken by individuals but further incentives must be set. In
      order to provide individuals with detailed information about their mitigation
      options, we took the results from a survey of environmental behavior of 3369
      Swiss Citizens, and combined them with life cycle assessment. Our results from
      this bottom-up approach show a huge bandwidth of the ecological footprints among
      the individuals interviewed. We conclude that a continuous consumption of not
      more than 2000 W per person seems possible for the major part of the population
      in this society. However, it will be far more difficult not to exceed 1 ton CO2
      per capita.

PMID- 23548148
TI  - Clinical validation of the AMTAS automated audiometer.
AB  - OBJECTIVE: To validate the air- and bone-conduction AMTAS automated audiometry
      system. DESIGN: Prospective study. Test-retest reliability was determined by
      assessing adults with AMTAS air- and bone-conduction audiometry. Accuracy was
      determined by comparing AMTAS and manual audiometry conducted on adults. AMTAS
      testing was conducted in a quiet room and manual audiometry in a sound booth.
      STUDY SAMPLE: Ten participants for test-retest reliability tests and 44
      participants to determine accuracy were included. Participants had varying
      degrees of hearing loss. RESULTS: For test-retest reliability the overall
      difference in air-conduction hearing thresholds (n = 119) was 0.5 dB. The spread
      of differences (standard deviation of absolute differences) was 4.9 dB. For bone
      conduction thresholds (n = 99) the overall difference was - 0.2 dB, and the
      spread of differences 4.5 dB. For accuracy the overall difference in air
      conduction hearing thresholds (n = 509) between the two techniques was 0.1 dB.
      The spread of differences was 6.4 dB. For bone-conduction thresholds (n = 295)
      the overall difference was 0 dB, and the spread of differences 7.7 dB.
      CONCLUSIONS: Variations between air- and bone-conduction audiometry for automated
      and manual audiometry were within normally accepted limits for audiometry.
      However, AMTAS thresholds were elevated but not significantly different compared
      to other contemporary studies that included an automated audiometer.

PMID- 23548149
TI  - PFKFB3 activation in cancer cells by the p38/MK2 pathway in response to stress
      stimuli.
AB  - PFK-2/FBPase-2 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) catalyses
      the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate), a key
      modulator of glycolysis and gluconeogenesis. The PFKFB3 gene is involved in cell
      proliferation owing to its role in carbohydrate metabolism. In the present study
      we analysed the mechanism of regulation of PFKFB3 as an immediate early gene
      controlled by stress stimuli that activates the p38/MK2 [MAPK (mitogen-activated
      protein kinase)-activated protein kinase 2] pathway. We report that exposure of
      HeLa and T98G cells to different stress stimuli (NaCl, H2O2, UV radiation and
      anisomycin) leads to a rapid increase (15-30 min) in PFKFB3 mRNA levels. The use
      of specific inhibitors in combination with MK2-deficient cells implicate control
      by the protein kinase MK2. Transient transfection of HeLa cells with deleted gene
      promoter constructs allowed us to identify an SRE (serum-response element) to
      which SRF (serum-response factor) binds and thus transactivates PFKFB3 gene
      transcription. Direct binding of phospho-SRF to the SRE sequence (-918 nt) was
      confirmed by ChIP (chromatin immunoprecipiation) assays. Moreover, PFKFB3
      isoenzyme phosphorylation at Ser461 by MK2 increases PFK-2 activity. Taken
      together, the results of the present study suggest a multimodal mechanism of
      stress stimuli affecting PFKFB3 transcriptional regulation and kinase activation
      by protein phosphorylation, resulting in an increase in Fru-2,6-P2 concentration
      and stimulation of glycolysis in cancer cells.

PMID- 23548150
TI  - Analysis of abstract and concrete word processing in persons with aphasia and age
      matched neurologically healthy adults using fMRI.
AB  - The concreteness effect occurs in both normal and language-disordered
      populations. Research suggests that abstract and concrete concepts elicit
      differing neural activation patterns in healthy young adults, but this is
      undocumented in persons with aphasia (PWA). Three PWA and three age-matched
      controls were scanned using fMRI while processing abstract and concrete words.
      Consistent with current theories of abstract and concrete word processing,
      abstract words elicited activation in verbal areas, whereas concrete words
      additionally activated multimodal association areas. PWA show greater differences
      in neural activation than age-matched controls between abstract and concrete
      words, possibly due to an exaggerated concreteness effect. 

PMID- 23548151
TI  - Reference change values for insulin and insulin-like growth factor binding
      protein-1 (IGFBP-1) in individuals with varying degrees of glucose tolerance.
AB  - BACKGROUND: The reference change value (RCV) is an important parameter of
      biological variation used to assess the significance of differences between
      consecutive results obtained in a single individual. This study evaluated the RCV
      for insulin-like growth factor binding protein-1 (IGFBP-1) and fasting serum
      insulin (FSI) in individuals with different degrees of glucose tolerance.
      METHODS: IGFBP-1 and FSI concentrations were measured in 33 fasting subjects who
      had two blood samples taken 10 days apart. Subjects were distributed in the
      following categories: Normal glucose tolerance (NGT), n = 15, impaired fasting
      glucose (IFG), n = 9 and impaired glucose tolerance (IGT), n = 9. RESULTS: The
      RCV values for IGFBP-1 were 59.9%, 83.2% and 93.0% and for FSI were 68.5%, 79.0%
      and 93.4% for subjects with NGT, IFG and IGT respectively. CONCLUSIONS: The RCVs
      for IGFBP-1 and FSI increase with deteriorating glucose tolerance. When
      monitoring IGFBP-1 and FSI, changes in concentrations should be interpreted using
      glycaemic category-specific RCV values.

PMID- 23548152
TI  - Experimental induction and oral transmission of avian AA amyloidosis in
      vaccinated white hens.
AB  - Avian AA amyloidosis is commonly observed in adult birds afflicted with bacterial
      infections or chronic inflammatory disorders. Experimental AA amyloidosis in
      birds can be induced by repeated inflammatory stimulation, such as injection with
      casein or vaccination with oil-emulsified bacterins. However, the transmission of
      amyloidosis among avian species has not been studied well to date. In the present
      study, we confirm the potential induction of avian AA amyloidosis by inoculation
      of Salmonella enteritidis (SE) vaccine or Mycoplasma gallisepticum vaccine. To
      determine the transmission of chicken AA amyloidosis among white hens, we induced
      experimental AA amyloidosis in vaccinated chickens by intravenous or oral
      administration of chicken AA fibrils. Amyloid deposits were observed in chickens
      injected with SE and inoculated with chicken AA fibrils intravenously (21/26:
      81%) and orally (8/12: 67%). These results suggest that chicken AA amyloidosis
      can be induced by vaccinations, and may be transmitted among like species by oral
      administration.

PMID- 23548153
TI  - Targeting both IGF-1R and mTOR synergistically inhibits growth of renal cell
      carcinoma in vitro.
AB  - BACKGROUND: Advanced or metastatic renal cell carcinoma (RCC) has a poor
      prognosis, because it is relatively resistant to conventional chemotherapy or
      radiotherapy. Treatments with human interferon-alpha2b alone or in combination
      with mammalian target of rapamycin (mTOR) inhibitors have led to only a modest
      improvement in clinical outcome. One observation made with mTOR inhibitors is
      that carcinomas can overcome these inhibitory effects by activating the insulin
      like growth factor-I (IGF-I) signaling pathway. Clinically, there is an
      association of IGF-I receptor (IGF-IR) expression in RCC and poor long-term
      patient survival. We have developed a humanized anti-IGF-IR monoclonal antibody,
      hR1, which binds to RCC, resulting in effective down-regulation of IGF-IR and
      moderate inhibition of cell proliferation in vitro. In this work, we evaluate the
      anti-tumor activity of two novel IGF-1R-targeting agents against renal cell
      carcinoma given alone or in combination with an mTOR inhibitor. METHODS: hR1 was
      linked by the DOCK-AND-LOCKTM (DNLTM) method to four Fabs of hR1, generating Hex
      hR1, or to four molecules of interferon-alpha2b, generating 1R-2b. Eight human
      RCC cell lines were screened for IGF-1R expression and sensitivity to treatment
      with hR1 in vitro. Synergy with an mTOR inhibitor, temsirolimus, was tested in a
      cell line (ACHN) with low sensitivity to hR1. RESULTS: Hex-hR1 induced the down
      regulation of IGF-IR at 10-fold lower concentrations compared to the parental
      hR1. Sensitivity to growth inhibition mediated by hR1 and Hex-hR1 treatments
      correlated with IGF-1R expression (higher expression was more sensitive). The
      potency of 1R-2b to inhibit the in vitro growth of RCC was also demonstrated in
      two human cell lines, ACHN and 786-O, with EC50-values of 63 and 48 pM,
      respectively. When combined with temsirolimus, a synergistic growth-inhibition
      with hR1, Hex-hR1, and 1R-2b was observed in ACHN cells at concentrations as low
      as 10 nM for hR1, 1 nM for Hex-hR1, and 2.6 nM for 1R-2b. CONCLUSIONS: Both Hex
      hR1 and 1R-2b proved to be more potent than parental hR1 in inhibiting growth of
      RCC in vitro. Synergy was achieved when each of the three hR1-based agents was
      combined with temsirolimus, suggesting a new approach for treating RCC.

PMID- 23548154
TI  - Supramolecular autoregulation.
AB  - Enzyme activity in biological systems is often governed by control mechanisms in
      which the catalytic properties are made sensitive or insensitive to differences
      in enzyme or substrate concentration. Here, we report the first supramolecular
      system where the catalytic activity is made concentration independent through the
      use of newly designed inhibitor molecules. The precise concentration dependence
      of coupled supramolecular equilibriums between free catalyst, inhibited catalyst,
      active inhibitor, and inactive inhibitor allows to keep the concentration of free
      catalyst at 1 mM in a broad concentration range, yielding an autoregulated
      catalytic system.

PMID- 23548155
TI  - A unified approach for debugging is-a structure and mappings in networked
      taxonomies.
AB  - BACKGROUND: With the increased use of ontologies and ontology mappings in
      semantically-enabled applications such as ontology-based search and data
      integration, the issue of detecting and repairing defects in ontologies and
      ontology mappings has become increasingly important. These defects can lead to
      wrong or incomplete results for the applications. RESULTS: We propose a unified
      framework for debugging the is-a structure of and mappings between taxonomies,
      the most used kind of ontologies. We present theory and algorithms as well as an
      implemented system RepOSE, that supports a domain expert in detecting and
      repairing missing and wrong is-a relations and mappings. We also discuss two
      experiments performed by domain experts: an experiment on the Anatomy ontologies
      from the Ontology Alignment Evaluation Initiative, and a debugging session for
      the Swedish National Food Agency. CONCLUSIONS: Semantically-enabled applications
      need high quality ontologies and ontology mappings. One key aspect is the
      detection and removal of defects in the ontologies and ontology mappings. Our
      system RepOSE provides an environment that supports domain experts to deal with
      this issue. We have shown the usefulness of the approach in two experiments by
      detecting and repairing circa 200 and 30 defects, respectively.

PMID- 23548156
TI  - Implementation of the CDC translational informatics platform--from genetic
      variants to the national Swedish Rheumatology Quality Register.
AB  - BACKGROUND: Sequencing of the human genome and the subsequent analyses have
      produced immense volumes of data. The technological advances have opened new
      windows into genomics beyond the DNA sequence. In parallel, clinical practice
      generate large amounts of data. This represents an underused data source that has
      much greater potential in translational research than is currently realized. This
      research aims at implementing a translational medicine informatics platform to
      integrate clinical data (disease diagnosis, diseases activity and treatment) of
      Rheumatoid Arthritis (RA) patients from Karolinska University Hospital and their
      research database (biobanks, genotype variants and serology) at the Center for
      Molecular Medicine, Karolinska Institutet. METHODS: Requirements engineering
      methods were utilized to identify user requirements. Unified Modeling Language
      and data modeling methods were used to model the universe of discourse and data
      sources. Oracle11g were used as the database management system, and the clinical
      development center (CDC) was used as the application interface. Patient data were
      anonymized, and we employed authorization and security methods to protect the
      system. RESULTS: We developed a user requirement matrix, which provided a
      framework for evaluating three translation informatics systems. The
      implementation of the CDC successfully integrated biological research database
      (15172 DNA, serum and synovial samples, 1436 cell samples and 65 SNPs per
      patient) and clinical database (5652 clinical visit) for the cohort of 379
      patients presents three profiles. Basic functionalities provided by the
      translational medicine platform are research data management, development of
      bioinformatics workflow and analysis, sub-cohort selection, and re-use of
      clinical data in research settings. Finally, the system allowed researchers to
      extract subsets of attributes from cohorts according to specific biological,
      clinical, or statistical features. CONCLUSIONS: Research and clinical database
      integration is a real challenge and a road-block in translational research.
      Through this research we addressed the challenges and demonstrated the usefulness
      of CDC. We adhered to ethical regulations pertaining to patient data, and we
      determined that the existing software solutions cannot meet the translational
      research needs at hand. We used RA as a test case since we have ample data on
      active and longitudinal cohort.

PMID- 23548157
TI  - Accurate determination of the reaction course in HY2 <-> Y + YH (Y = O, S):
      detailed analysis of the covalent- to hydrogen-bonding transition.
AB  - The accurate prediction of a bond-breaking/bond-forming reaction course is useful
      but very difficult. Toward this goal, a cost-effective multireference scheme (A.
      J. C. Varandas, J. Chem. Theory Comput. 2012, 8, 428) is tested that provides a
      generalization of the Hartree-Fock plus dispersion model for closed-shell
      interactions, and hence is based on the popular but largely untested idea of
      performing single point calculations with a high-level method at stationary
      points or along paths located using a lower level method. The energetics so
      calculated for the reaction HO2 <-> O + OH is predicted in excellent agreement
      with the experimental data, whereas the reaction path shows a scar at the onset
      of hydrogen-bonding: a weak van der Waals type minimum separated from the deep
      covalent well by a small barrier, all below the O + OH asymptote. The O-OH long
      range interaction potential is also examined and possible implications in
      reaction dynamics discussed. Corresponding attributes for the reaction HS2 <-> S
      + SH are predicted, in good agreement with the best theoretical and experimental
      results. A perspective on the general utility of the approach is presented.

PMID- 23548158
TI  - Predictive models for mixed-matrix membrane performance: a review.

PMID- 23548159
TI  - Mapping the lignin distribution in pretreated sugarcane bagasse by confocal and
      fluorescence lifetime imaging microscopy.
AB  - BACKGROUND: Delignification pretreatments of biomass and methods to assess their
      efficacy are crucial for biomass-to-biofuels research and technology. Here, we
      applied confocal and fluorescence lifetime imaging microscopy (FLIM) using one-
      and two-photon excitation to map the lignin distribution within bagasse fibers
      pretreated with acid and alkali. The evaluated spectra and decay times are
      correlated with previously calculated lignin fractions. We have also investigated
      the influence of the pretreatment on the lignin distribution in the cell wall by
      analyzing the changes in the fluorescence characteristics using two-photon
      excitation. Eucalyptus fibers were also analyzed for comparison. RESULTS:
      Fluorescence spectra and variations of the decay time correlate well with the
      delignification yield and the lignin distribution. The decay dependences are
      considered two-exponential, one with a rapid (tau1) and the other with a slow
      (tau2) decay time. The fastest decay is associated to concentrated lignin in the
      bagasse and has a low sensitivity to the treatment. The fluorescence decay time
      became longer with the increase of the alkali concentration used in the
      treatment, which corresponds to lignin emission in a less concentrated
      environment. In addition, the two-photon fluorescence spectrum is very sensitive
      to lignin content and accumulation in the cell wall, broadening with the acid
      pretreatment and narrowing with the alkali one. Heterogeneity of the pretreated
      cell wall was observed. CONCLUSIONS: Our results reveal lignin domains with
      different concentration levels. The acid pretreatment caused a disorder in the
      arrangement of lignin and its accumulation in the external border of the cell
      wall. The alkali pretreatment efficiently removed lignin from the middle of the
      bagasse fibers, but was less effective in its removal from their surfaces. Our
      results evidenced a strong correlation between the decay times of the lignin
      fluorescence and its distribution within the cell wall. A new variety of lignin
      fluorescence states were accessed by two-photon excitation, which allowed an even
      broader, but complementary, optical characterization of lignocellulosic
      materials. These results suggest that the lignin arrangement in untreated bagasse
      fiber is based on a well-organized nanoenvironment that favors a very low level
      of interaction between the molecules.

PMID- 23548161
TI  - Can the 12-item General Health Questionnaire be used to identify medical students
      who might 'struggle' on the medical course? A prospective study on two cohorts.
AB  - BACKGROUND: Students who fail to thrive on the Nottingham undergraduate medical
      course frequently suffer from anxiety, depression or other mental health
      problems. These difficulties may be the cause, or the result of, academic
      struggling. Early detection of vulnerable students might direct pastoral care and
      remedial support to where it is needed. We investigated the use of the short-form
      General Health Questionnaire (GHQ-12) as a possible screening tool. METHODS: Two
      consecutive cohorts (2006 and 2007) were invited to complete the GHQ-12. The
      questionnaire was administered online, during the second semester (after semester
      1 exams) for the 2006 cohort and during the first semester for the 2007 cohort.
      All data were held securely and confidentially. At the end of the course, GHQ
      scores were examined in relation to course progress. RESULTS: 251 students
      entered the course in 2006 and 254 in 2007; 164 (65%) and 160 (63%),
      respectively, completed the GHQ-12. In both cohorts, the study and non-study
      groups were very similar in terms of pre-admission socio-demographic
      characteristics and overall course marks. In the 2006 study group, the GHQ Likert
      score obtained part-way through the first year was negatively correlated with
      exam marks during Years 1 and 2, but the average exam mark in semester 1 was the
      sole independent predictor of marks in semester 2 and Year 2. No correlations
      were found for the 2007 study group but the GHQ score was a weak positive
      predictor of marks in semester 2, with semester 1 average exam mark again being
      the strongest predictor. A post-hoc moderated-mediation analysis suggested that
      significant negative associations of GHQ scores with semester 1 and 2 exams
      applied only to those who completed the GHQ after their semester 1 exams.
      Students who were identified as GHQ 'cases' in the 2006 group were statistically
      less likely to complete the course on time (OR=4.74, p 0.002). There was a non
      significant trend in the same direction in the 2007 group. CONCLUSIONS: Results
      from two cohorts provide insufficient evidence to recommend the routine use of
      the GHQ-12 as a screening tool. The timing of administration could have a
      critical influence on the results, and the theoretical and practical implications
      of this finding are discussed. Low marks in semester 1 examinations seem be the
      best single indicator of students at risk for subsequent poor performance.

PMID- 23548162
TI  - A genotype-specific, randomized controlled behavioral intervention to improve the
      neuroemotional outcome of cardiac surgery: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Cardiac surgery is one of the most commonly performed surgical
      procedures worldwide with >700,000 surgeries in 2006 in the US alone. Cardiac
      surgery results in a considerable exposure to physical and emotional stress;
      stress-related disorders such as depression or post-traumatic stress disorder are
      the most common adverse outcomes of cardiac surgery, seen in up to 20% of
      patients. Using information from a genome-wide association study to characterize
      genetic effects on emotional memory, we recently identified a single nucleotide
      polymorphism of the glucocorticoid receptor gene (the Bcll single nucleotide
      polymorphism) as a significant genetic risk factor for traumatic memories from
      cardiac surgery and symptoms of post-traumaticstress disorder. The Bcll high-risk
      genotype (Bcll GG) has a prevalence of 16.6% in patients undergoing cardiac
      surgery and is associated with increased glucocorticoid receptor signaling under
      stress. Concomitant animal experiments have confirmed an essential role of
      glucocorticoid receptor activation for traumatic memory formation during
      stressful experiences. Early cognitive behavioral intervention has been shown to
      prevent stress-related disorders after heart surgery. METHODS/DESIGN: The
      proposed study protocol is based on the above mentioned earlier findings from
      animal experiments and preclinical studies in volunteers. Patients (n = 872) will
      be genotyped for the Bcll single nucleotide polymorphism before surgery, which
      should result in 120 homozygous high-risk carriers of the Bcll GG allele and 240
      randomly selected low-risk heterozygous or non-carriers of the single nucleotide
      polymorphism. All patients will then undergo randomization to either cognitive
      behavioral intervention or a control intervention consisting of non-specific
      general information about the role of stress in heart disease. The primary
      efficacy endpoint will be post-traumatic stress levels at one year after surgery
      as determined by a standardized questionnaire that has been specifically
      validated in patients after critical illness. DISCUSSION: The proposed randomized
      controlled trial intends to demonstrate that a preoperatively administered
      minimal cognitive behavioral intervention targeted to homozygous carriers of the
      Bcll *G high-risk allele reduces traumatic memories and post-traumatic stress
      disorder symptoms after heart surgery to a level seen in non-carriers of the
      mutation, and thus improves the neuroemotional outcome of cardiac surgery. TRIAL
      REGISTRATION NUMBER: The trial will be registered at
      http://www.clinicaltrials.gov/ before commencing with the study.

PMID- 23548163
TI  - Simulated microgravity facilitates cell migration and neuroprotection after bone
      marrow stromal cell transplantation in spinal cord injury.
AB  - INTRODUCTION: Recently, cell-based therapy has gained significant attention for
      the treatment of central nervous system diseases. Although bone marrow stromal
      cells (BMSCs) are considered to have good engraftment potential, challenges due
      to in vitro culturing, such as a decline in their functional potency, have been
      reported. Here, we investigated the efficacy of rat BMSCs (rBMSCs) cultured under
      simulated microgravity conditions, for transplantation into a rat model of spinal
      cord injury (SCI). METHODS: rBMSCs were cultured under two different conditions:
      standard gravity (1G) and simulated microgravity attained by using the 3D
      clinostat. After 7 days of culture, the rBMSCs were analyzed morphologically,
      with RT-PCR and immunostaining, and were used for grafting. Adult rats were used
      for constructing SCI models by using a weight-dropping method and were grouped
      into three experimental groups for comparison. rBMSCs cultured under 1 g and
      simulated microgravity were transplanted intravenously immediately after SCI. We
      evaluated the hindlimb functional improvement for 3 weeks. Tissue repair after
      SCI was examined by calculating the cavity area ratio and immunohistochemistry.
      RESULTS: rBMSCs cultured under simulated microgravity expressed Oct-4 and CXCR4,
      in contrast to those cultured under 1 g conditions. Therefore, rBMSCs cultured
      under simulated microgravity were considered to be in an undifferentiated state
      and thus to possess high migration ability. After transplantation, grafted rBMSCs
      cultured under microgravity exhibited greater survival at the periphery of the
      lesion, and the motor functions of the rats that received these grafts improved
      significantly compared with the rats that received rBMSCs cultured in 1 g. In
      addition, rBMSCs cultured under microgravity were thought to have greater trophic
      effects on reestablishment and survival of host spinal neural tissues because
      cavity formations were reduced, and apoptosis-inhibiting factor expression was
      high at the periphery of the SCI lesion. CONCLUSIONS: Here we show that
      transplantation of rBMSCs cultured under simulated microgravity facilitates
      functional recovery from SCI rather than those cultured under 1 g conditions.

PMID- 23548164
TI  - Neoclerodanes as atypical opioid receptor ligands.
AB  - The neoclerodane diterpene salvinorin A is the major active component of the
      hallucinogenic mint plant Salvia divinorum Epling and Jativa (Lamiaceae). Since
      the finding that salvinorin A exerts its potent psychotropic actions through the
      activation of opioid receptors, the site of action of morphine and related
      analogues, there has been much interest in elucidating the underlying mechanisms
      behind its effects. These effects are particularly remarkable because (1)
      salvinorin A is the first reported non-nitrogenous opioid receptor agonist and
      (2) its effects are not mediated through the previously investigated targets of
      psychotomimetics. This Perspective outlines our research program, illustrating a
      new direction to the development of tools to further elucidate the biological
      mechanisms of drug tolerance and dependence. The information gained from these
      efforts is expected to facilitate the design of novel agents to treat pain, drug
      abuse, and other central nervous system disorders.

PMID- 23548165
TI  - Bioavailability, metabolism and disposition of oral pazopanib in patients with
      advanced cancer.
AB  - 1. Pazopanib (Votrient) is an oral tyrosine kinase inhibitor that was recently
      approved for the treatment of renal cell carcinoma and soft tissue sarcoma. 2. In
      this two-part study, we investigated the metabolism, disposition of
      [(14)C]pazopanib, and the oral bioavailability of pazopanib tablets in patients
      with advanced cancer. 3. In part A, three men each received a single oral dose of
      [(14)C]pazopanib in suspension (400 mg, 70 uCi). Pazopanib was the predominant
      drug-related component in circulation. Two metabolites derived from hydroxylation
      and one from N-demethylation were also circulating, but were minor, each
      accounting for <5% of plasma radioactivity. Faecal elimination predominated,
      accounting for 82.2% of the administered radio-dose, with negligible renal
      elimination (2.6% of dose). Pazopanib was primarily excreted as the unchanged
      drug in faeces (67% of dose). 4. In part B, seven additional patients received a
      single intravenous administration of 5 mg pazopanib (day 1) followed by oral
      administration of 800 mg pazopanib tablet once daily for 26 days (days 3 or 5
      28). In the three evaluable patients from part B, pazopanib had a slow plasma
      clearance and a small volume of distribution. The absolute oral bioavailability
      of the 800 mg pazopanib tablet ranged from 14% to 39%.

PMID- 23548166
TI  - Distinct photolytic mechanisms and products for different dissociation species of
      ciprofloxacin.
AB  - As many antibiotics are ionizable and may have different dissociation forms in
      the aquatic environment, we hypothesized that the different dissociation species
      have disparate photolytic pathways, products, and kinetics, and adopted
      ciprofloxacin (CIP) as a case to test this hypothesis. Simulated sunlight
      experiments and matrix calculations were performed to differentiate the
      photolytic reactivity for each dissociation species (H4CIP(3+), H3CIP(2+),
      H2CIP(+), HCIP(0), and CIP(-)). The results prove that the five dissociation
      species do have dissimilar photolytic kinetics and products. H4CIP(3+) mainly
      undergoes stepwise cleavage of the piperazine ring, while H2CIP(+) mainly
      undergoes defluorination. For H3CIP(2+), HCIP(0), and CIP(-), the major
      photolytic pathway is oxidation. By density functional theory calculation, we
      clarified the defluorination mechanisms for the five dissociation species at the
      excited triplet states: All the five species can defluorinate by reaction with
      hydroxide ions (OH(-)) to form hydroxylated products, and H2CIP(+) can also
      undergo C-F bond cleavage to produce F(-) and a carbon-centered radical. This
      study is a first attempt to differentiate the photolytic products and mechanisms
      for different dissociation species of ionizable compounds. The results imply that
      for accurate ecological risk assessment of ionizable emerging pollutants, it is
      necessary to investigate the environmental photochemical behavior of all
      dissociation species.

PMID- 23548160
TI  - Method parameters' impact on mortality and variability in rat stroke experiments:
      a meta-analysis.
AB  - BACKGROUND: Even though more than 600 stroke treatments have been shown effective
      in preclinical studies, clinically proven treatment alternatives for cerebral
      infarction remain scarce. Amongst the reasons for the discrepancy may be
      methodological shortcomings, such as high mortality and outcome variability, in
      the preclinical studies. A common approach in animal stroke experiments is that
      A) focal cerebral ischemia is inflicted, B) some type of treatment is
      administered and C) the infarct sizes are assessed. However, within this
      paradigm, the researcher has to make numerous methodological decisions, including
      choosing rat strain and type of surgical procedure. Even though a few studies
      have attempted to address the questions experimentally, a lack of consensus
      regarding the optimal methodology remains. METHODS: We therefore meta-analyzed
      data from 502 control groups described in 346 articles to find out how rat
      strain, procedure for causing focal cerebral ischemia and the type of filament
      coating affected mortality and infarct size variability. RESULTS: The Wistar
      strain and intraluminal filament procedure using a silicone coated filament was
      found optimal in lowering infarct size variability. The direct and endothelin
      methods rendered lower mortality rate, whereas the embolus method increased it
      compared to the filament method. CONCLUSIONS: The current article provides means
      for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols
      to minimize infarct size variability and mortality.

PMID- 23548167
TI  - Total testosterone levels, metabolic parameters, cardiac remodeling and exercise
      capacity in coronary artery disease patients with different stages of glucose
      tolerance.
AB  - OBJECTIVE AND METHODS: The correlation between total testosterone levels,
      exercise capacity, and metabolic and echocardiographic parameters was studied in
      1097 male subjects with coronary artery disease (CAD) and different stages of
      glucose tolerance. RESULTS: Testosterone level was the lowest among diabetics as
      compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity
      were the highest in the subjects with the lowest testosterone. Independent of
      adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001)
      among diabetic and control groups in the lowest, and HbA1c values (P < 0.001)
      higher among diabetics in the lowest, than in the highest testosterone tertile.
      Controls and prediabetic subjects with the lowest testosterone levels had the
      lowest HDL-cholesterol levels, and controls also the highest triglycerides. An
      association between low testosterone level and low maximal exercise capacity was
      observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of
      adiposity and metabolic parameters, low testosterone levels were associated with
      the highest septal wall thickness (P < 0.03) among diabetics. CONCLUSION: A
      negative correlation between low testosterone and dysmetabolic features was
      observed. Independent of metabolic status, low plasma testosterone seems to be an
      indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD
      patients with type II diabetes.

PMID- 23548168
TI  - CE hospital service utilization is reduced following neuropsychological
      evaluation in a sample of U.S. veterans.
AB  - The aim of this study was to evaluate the objective value of neuropsychological
      evaluation (NPE) through reduction in Emergency Room (ER) visits and
      hospitalizations. Retrospective analysis examined trends in ER visits and
      hospitalizations in 440 U.S. veterans who completed NPE between the years of 2003
      and 2010. Within-subjects comparisons showed significant decreases in incidence
      of hospitalization and length of hospitalization in the year after evaluation
      compared to the year prior. Mean number of hospitalizations declined from 0.31
      (SD = 0.64) pre-NPE to 0.22 (SD = 0.59) post-NPE; there were a total of 41 fewer
      hospitalizations in the year following NPE. Mean length of hospitalization
      decreased from 1.9 days (SD = 5.6) pre-NPE to 1.06 days (SD = 3.9) post-NPE;
      there were a total of 368 fewer days of hospitalization post-NPE. This reduction
      was not attributable to age or time. Incidence of ER visits also decreased from
      pre-NPE (M = 0.74, SD = 1.3) to post-evaluation (M = 0.69, SD = 1.3), though this
      was not significant. These findings provide preliminary evidence of the clinical
      and potential economic value of neuropsychological services within a medical
      setting. Follow-up studies should examine individual and exam-specific factors
      that may contribute to reduced utilization. 

PMID- 23548169
TI  - Practice patterns and perceived impact of clinical nurse specialist roles in
      Canada: results of a national survey.
AB  - BACKGROUND: Clinical nurse specialists are recognized internationally for
      providing an advanced level of practice. They positively impact the delivery of
      healthcare services by using specialty-specific expert knowledge and skills, and
      integrating competencies as clinicians, educators, researchers, consultants and
      leaders. Graduate-level education is recommended for the role but many countries
      do not have formal credentialing mechanisms for clinical nurse specialists.
      Previous studies have found that clinical nurse specialist roles are poorly
      understood by stakeholders. Few national studies have examined the utilization of
      clinical nurse specialists. OBJECTIVE: To identify the practice patterns of
      clinical nurse specialists in Canada. DESIGN: A descriptive cross-sectional
      survey. PARTICIPANTS: Self-identified clinical nurse specialists in Canada.
      METHODS: A 50-item self-report questionnaire was developed, pilot-tested in
      English and French, and administered to self-identified clinical nurse
      specialists from April 2011 to August 2011. Data were analyzed using descriptive
      and inferential statistics and content analysis. RESULTS: The actual number of
      clinical nurse specialists in Canada remains unknown. The response rate using the
      number of registry-identified clinical nurse specialists was 33% (804/2431). Of
      this number, 608 reported working as a clinical nurse specialist. The response
      rate for graduate-prepared clinical nurse specialists was 60% (471/782). The
      practice patterns of clinical nurse specialists varied across clinical
      specialties. Graduate-level education influenced their practice patterns. Few
      administrative structures and resources were in place to support clinical nurse
      specialist role development. The lack of title protection resulted in confusion
      around who identifies themselves as a clinical nurse specialist and consequently
      made it difficult to determine the number of clinical nurse specialists in
      Canada. CONCLUSIONS: This is the first national survey of clinical nurse
      specialists in Canada. A clearer understanding of these roles provides
      stakeholders with much needed information about clinical nurse specialist
      practice patterns. Such information can inform decisions about policies,
      education and organizational supports to effectively utilize this role in
      healthcare systems. This study emphasizes the need to develop standardized
      educational requirements, consistent role titles and credentialing mechanisms to
      facilitate the identification and comparison of clinical nurse specialist roles
      and role outcomes internationally.

PMID- 23548170
TI  - The challenges of achieving person-centred care in acute hospitals: a qualitative
      study of people with dementia and their families.
AB  - BACKGROUND: Person-centred care has been identified as the ideal approach to
      caring for people with dementia. Developed in relation to long stay settings,
      there are challenges to its implementation in acute settings. However,
      international policy indicates that acute care for people with dementia should be
      informed by the principles of person-centred care and interventions should be
      designed to sustain their personhood. OBJECTIVES: Using Kitwood's five dimensions
      of personhood as an a priori framework, the aim of this paper was to explore the
      way in which current approaches to care in acute settings had the potential to
      enhance personhood in older adults with dementia. DESIGN: Data collected to
      explore the current experiences of people with dementia, family carers and co
      patients (patients sharing the ward with people with mental health problems)
      during hospitalisation for acute illness were analysed using a dementia framework
      that described core elements of person centred care for people with dementia.
      SETTINGS: Recruitment was from two major hospitals within the East Midlands
      region of the UK, focusing on patients who were admitted to general medical,
      health care for older people, and orthopaedic wards. PARTICIPANTS: Participants
      were people aged over 70 on the identified acute wards, identified through a
      screeing process as having possible mental health problems. 34 patients and their
      relatives were recruited: this analysis focused on the 29 patients with cognitive
      impairment. METHOD: The study involved 72 h of ward-based non-participant
      observations of care complemented by 30 formal interviews after discharge
      concerning the experiences of the 29 patients with cognitive impairment. Analysis
      used the five domains of Kitwood's model of personhood as an a priori framework:
      identity, inclusion, attachment, comfort and occupation. RESULTS: While there
      were examples of good practice, health care professionals in acute settings were
      not grasping all opportunities to sustain personhood for people with dementia.
      CONCLUSIONS: There is a need for the concept of person-centred care to be valued
      at the level of both the individual and the organisation/team for people with
      dementia to have appropriate care in acute settings.

PMID- 23548171
TI  - Inhibition of Plasmodium falciparum CDPK1 by conditional expression of its J
      domain demonstrates a key role in schizont development.
AB  - PfCDPK1 [Plasmodium falciparum CDPK1 (calcium-dependent protein kinase 1)] is
      highly expressed in parasite asexual blood and mosquito stages. Its role is still
      poorly understood, but unsuccessful gene knockout attempts suggest that it is
      essential for parasite replication and/or RBC (red blood cell) invasion. In the
      present study, by tagging endogenous CDPK1 with GFP (green fluorescent protein),
      we demonstrate that CDPK1 localizes to the parasite plasma membrane of
      replicating and invasive forms as well as very young intracellular parasites and
      does not appear to be exported into RBCs. Although a knockdown of endogenous
      CDPK1 was achieved using a destabilization domain, parasites tolerated reduced
      expression without displaying a phenotype. Because of this, the PfCDPK1 auto
      inhibitory J (junction) domain was explored as a means of achieving inducible and
      specific inhibition. Under in vitro conditions, a fusion protein comprising a J
      GFP fusion specifically bound to PfCDPK1 and inhibited its activity. This fusion
      protein was conditionally expressed in P. falciparum asexual blood stages under
      the regulation of a DD (destabilization domain) (J-GFP-DD). We demonstrate that J
      GFP-DD binds to CDPK1 and that this results in the arrest of parasite development
      late in the cell cycle during early schizogony. These data point to an early
      schizont function for PfCDPK1 and demonstrate that conditionally expressing auto
      inhibitory regions can be an effective way to address the function of Plasmodium
      enzymes.

PMID- 23548173
TI  - Risk scoring system to predict 3-year survival in patients treated for
      asymptomatic carotid stenosis.
AB  - OBJECTIVE: To identify risk factors and stratify their effect of compromising 3
      year survival in patients treated for asymptomatic carotid disease based upon
      recently updated guidelines from the Society for Vascular Surgery. METHODS:
      Outcomes of 506 patients who underwent carotid intervention for asymptomatic
      carotid disease (1999-2008) were analyzed. Hospital computerized medical records
      were reviewed. When local records were sparse, Social Security Death Index was
      queried to confirm mortality. Following multivariable Cox regression analysis, a
      score was assigned based on the calculated hazard ratio (HR) in the following
      fashion: HR 1.5-1.9 = 1 point; HR 2.0-3.0 = 2 points; and HR >3 = 3 points. The
      sum of those points comprised the final score for each patient. Kaplan-Meier
      analyses were then performed to delineate survival differences. RESULTS: Seventy
      patients (13.83%) did not survive beyond 3 years after the procedure. Age >80
      years (HR, 1.79; P = .05; score 1), diabetes mellitus (HR, 1.99; P < .05; score
      1), coronary artery intervention (HR, 2.03; P < .01; score 2), severe chronic
      kidney disease defined as glomerular filtration rate <30 and not on dialysis (HR,
      2.46; P = .03; score 2), dialysis patients (HR, 5.67; P = .001; score 3), and
      chronic obstructive pulmonary disease (HR, 3.53; P < .001; score 3) negatively
      influenced 3-year survival. Patients with score <=2 experienced 3-year mortality
      of 6.0%, whereas score >2 was associated with 31.6% 3-year mortality (HR, 6.10; P
      < .001). The score value was not associated with the stroke rate at any time
      point. The resultant score was validated in a separate population of patients
      with symptomatic carotid disease. CONCLUSIONS: This easy predictive score
      underscores the association of medical risk factors with decreased 3-year
      survival. This finding may impact future clinical decisions for management of
      asymptomatic carotid disease.

PMID- 23548172
TI  - Membrane Type 1 Matrix Metalloproteinase induces an epithelial to mesenchymal
      transition and cancer stem cell-like properties in SCC9 cells.
AB  - BACKGROUND: Tissue invasion and metastasis are acquired abilities of cancer and
      related to the death in oral squamous cell carcinoma (OSCC). Emerging
      observations indicate that the epithelial-to-mesenchymal transition (EMT) is
      associated with tumor progression and the generation of cells with cancer stem
      cells (CSCs) properties. Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) is a
      cell surface proteinase, which is involved in degrading extracellular matrix
      components that can promote tumor invasion and cell migration. METHODS: In the
      current study, we utilized SCC9 cells stably transfected with an empty vector
      (SCC9-N) or a vector encoding human MT1-MMP (SCC9-M) to study the role of MT1-MMP
      in EMT development. RESULTS: Upon up-regulation of MT1-MMP, SCC9-M cells
      underwent EMT, in which they presented a fibroblast-like phenotype and had a
      decreased expression of epithelial markers (E-cadherin, cytokeratin18 and beta
      catenin) and an increased expression of mesenchymal markers (vimentin and
      fibronectin). We further demonstrated that MT1-MMP-induced morphologic changes
      increased the level of Twist and ZEB, and were dependent on repressing the
      transcription of E-cadherin. These activities resulted in low adhesive, high
      invasive abilities of the SCC9-M cells. Furthermore, MT1-MMP-induced transformed
      cells exhibited cancer stem cell (CSC)-like characteristics, such as low
      proliferation, self-renewal ability, resistance to chemotherapeutic drugs and
      apoptosis, and expression of CSCs surface markers. CONCLUSIONS: In conclusion,
      our study indicates that overexpression of MT1-MMP induces EMT and results in the
      acquisition of CSC-like properties in SCC9 cells. Our growing understanding of
      the mechanism regulating EMT may provide new targets against invasion and
      metastasis in OSCC.

PMID- 23548174
TI  - Venous occlusion plethysmography in patients with post-thrombotic venous
      claudication.
AB  - OBJECTIVE: Post-thrombotic venous claudication is a serious condition that may be
      treated with iliac vein stenting or open surgery, and there is a need for
      hemodynamic tests in the preoperative evaluation. The purpose of this study was
      to describe the results of venous occlusion plethysmography in patients with
      venous claudication and to analyze the outflow curve to find variables that best
      describe the functional abnormality in this patient group. METHODS: Twenty-nine
      patients with previous deep venous thrombosis and with clinical evidence of
      venous claudication were retrospectively identified. The results of venous
      occlusion plethysmography in these patients were compared with results obtained
      in a group of 63 healthy control subjects of similar age and sex. Computerized
      strain-gauge plethysmography was used in a capacitance mode where the occlusion
      time is determined by an electronic detector allowing the maximal venous volume
      to be achieved in all limbs. Outflow volumes (OV1, OV4) and outflow fractions
      (OF1, OF4) were calculated at 1 and 4 seconds after cuff release. Outflow
      fraction is OV divided by maximal venous volume. RESULTS: Both outflow volumes
      and outflow fractions were significantly reduced in patients compared with
      healthy control subjects. Outflow fractions were more sensitive than outflow
      volumes in identifying patients with venous claudication. The most discriminating
      variable was OF4 that was reduced below the normal lower limit in 69% of the
      patients, most severely reduced in patients with severe claudication.
      CONCLUSIONS: Patients with venous claudication attributable to remaining post
      thrombotic iliofemoral obstructive disease are characterized by a functional
      disturbance shown with venous occlusion plethysmography as a reduced venous
      outflow during the initial 4 seconds following cuff release in relation to their
      true maximal venous volume. Our results suggest that venous occlusion
      plethysmography can be a valuable tool in the preoperative workup for selection
      of patients with iliofemoral vein obstruction that may benefit from venous
      intervention.

PMID- 23548175
TI  - Risk factors for incisional hernia repair after aortic reconstructive surgery in
      a nationwide study.
AB  - OBJECTIVE: Abdominal aortic aneurysm disease has been hypothesized as associated
      with the development of abdominal wall hernia. We evaluated the risk factors for
      incisional hernia repair after open elective aortic reconstructive surgery for
      aortoiliac occlusive disease and abdominal aortic aneurysm. METHODS: A
      retrospective analysis of prospectively recorded data in nationwide databases was
      carried out, with merged data from the Danish Vascular Registry (January 2006
      January 2012), the Danish Ventral Hernia Database (January 2007-January 2012),
      and the Danish National Patient Register (January 2007-January 2012) to obtain
      100% follow-up for incisional hernia repair in patients undergoing open elective
      aortic reconstructive surgery. The predefined risk factors of age, sex, American
      Association of Anesthesiologists score, body mass index, smoking status, type of
      aortic surgery, and type of incision were tested in a multivariate Cox regression
      model for the risk of incisional hernia repair. RESULTS: We identified 2597
      patients, of whom 838 and 1759 underwent open elective surgery for an aortoiliac
      occlusive disease and abdominal aortic aneurysm, respectively. The median follow
      up was 28.9 months (range, 0-71.6 months), and the cumulative risk of hernia
      repair after aortic reconstructive surgery was 10.4% after 6 years of follow-up.
      Body mass index >25.0 kg/m(2) (adjusted hazard ratio, 1.74; 95% confidence
      interval, 1.21-2.46) and abdominal aortic aneurysm repair (adjusted hazard ratio,
      1.58; 95% confidence interval, 1.06-2.35) were significantly associated with
      incisional hernia repair. CONCLUSIONS: High body mass index and abdominal aortic
      aneurysm repair were independent risk factors for a subsequent incisional hernia
      surgery in patients undergoing aortic reconstructive surgery.

PMID- 23548176
TI  - Highly automatic quantification of myocardial oedema in patients with acute
      myocardial infarction using bright blood T2-weighted CMR.
AB  - BACKGROUND: T2-weighted cardiovascular magnetic resonance (CMR) is clinically
      useful for imaging the ischemic area-at-risk and amount of salvageable myocardium
      in patients with acute myocardial infarction (MI). However, to date,
      quantification of oedema is user-defined and potentially subjective. METHODS: We
      describe a highly automatic framework for quantifying myocardial oedema from
      bright blood T2-weighted CMR in patients with acute MI. Our approach retains user
      input (i.e. clinical judgment) to confirm the presence of oedema on an image
      which is then subjected to an automatic analysis. The new method was tested on 25
      consecutive acute MI patients who had a CMR within 48 hours of hospital
      admission. Left ventricular wall boundaries were delineated automatically by
      variational level set methods followed by automatic detection of myocardial
      oedema by fitting a Rayleigh-Gaussian mixture statistical model. These data were
      compared with results from manual segmentation of the left ventricular wall and
      oedema, the current standard approach. RESULTS: The mean perpendicular distances
      between automatically detected left ventricular boundaries and corresponding
      manual delineated boundaries were in the range of 1-2 mm. Dice similarity
      coefficients for agreement (0=no agreement, 1=perfect agreement) between manual
      delineation and automatic segmentation of the left ventricular wall boundaries
      and oedema regions were 0.86 and 0.74, respectively. CONCLUSION: Compared to
      standard manual approaches, the new highly automatic method for estimating
      myocardial oedema is accurate and straightforward. It has potential as a generic
      software tool for physicians to use in clinical practice.

PMID- 23548177
TI  - Stochastic voyages into uncharted chemical space produce a representative library
      of all possible drug-like compounds.
AB  - The "small molecule universe" (SMU), the set of all synthetically feasible
      organic molecules of 500 Da molecular weight or less, is estimated to contain
      over 10(60) structures, making exhaustive searches for structures of interest
      impractical. Here, we describe the construction of a "representative universal
      library" spanning the SMU that samples the full extent of feasible small molecule
      chemistries. This library was generated using the newly developed Algorithm for
      Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two
      important contributions to chemical space exploration: it allows the systematic
      search of the unexplored regions of the small molecule universe, and it
      facilitates the mining of chemical libraries that do not yet exist, providing a
      near-infinite source of diverse novel compounds.

PMID- 23548179
TI  - Type I interferon in neurological disease-the devil from within.
AB  - The members of the type I interferon (IFN-I) family of cytokines are pleiotropic
      factors that have seminal roles in host defence, acting as antimicrobial and
      antitumor mediators as well as potent immunomodulatory factors that bridge the
      innate and adaptive immune responses. Despite these beneficial actions there is
      mounting evidence that link inappropriate or chronic production of IFN-I in the
      CNS to the development of a number of severe neuroinflammatory disorders. The
      most persuasive example is the genetically determined inflammatory
      encephalopathy, Aicardi-Goutieres syndrome (AGS) in which patients have
      chronically elevated IFN-alpha production in the CNS. The presentation of AGS can
      often mimic congenital viral infection, however, molecular genetic studies have
      identified mutations in six genes that can cause AGS, most likely via
      dysregulated nucleic acid metabolism and activation of the innate immune response
      leading to increased intrathecal production of IFN-alpha. The role of IFN-alpha
      as a pathogenic factor in AGS and other neurological disorders has gained
      considerable support from experimental studies. In particular, a transgenic mouse
      model with CNS-restricted production of IFN-alpha replicates many of the cardinal
      neuropathologic features of AGS and reveal IFN-I to be the "devil from within",
      mediating molecular and cellular damage within the CNS. Thus, targeting IFN-I may
      be an effective strategy for the treatment of AGS as well as some other
      autoimmune and infectious neurological "interferonopathies". 

PMID- 23548181
TI  - Metal oxides and oxysalts as anode materials for Li ion batteries.

PMID- 23548180
TI  - Conformational selection and induced fit in specific antibody and antigen
      recognition: SPE7 as a case study.
AB  - Antibody-antigen specific recognition is essential in autoimmunity. In this
      study, antibody SPE7 binding to protein antigens and to hapten molecules were
      carefully analyzed in order to gain insight into their binding mechanisms. X-ray
      crystal structures show that SPE7 can adopt at least four different
      conformations, as in the two observed free isomers (Ab(1) and Ab(2)) and the two
      observed bound conformers (Ab(3) and Ab(4)). Multidimensional scaling analysis
      reveals that antibody SPE7 may obey a global conformational selection mechanism
      upon its binding to an antigen. The conformations of key residue at the binding
      site (Trp93L) further reveals that bound isomer Ab(3) may come from free isomer
      Ab(2), and bound isomer Ab(4) from free isomer Ab(1). The average root-mean
      square deviation (RMSD) values between the bound isomers and the corresponding
      free isomers and Kolmogorov-Smimov P test analysis indicate that the antibody may
      also follow a local induced fit mechanism at the binding interface. Quantitative
      analysis indicates that the magnitude of the local induced fit interaction at the
      binding site is more pronounced than that of the global conformational selection
      interaction. These conclusions are further supported by high-temperature
      unbinding kinetics analysis. The computational methods proposed here can also be
      used to study the specific recognitions between other antibody and antigen
      systems.

PMID- 23548178
TI  - A (selective) history of Australian involvement in cytokine biology.
AB  - This review focuses on contributions to cytokine biology made by Australians in
      Australia. It is clearly biased by my own experiences and selective recollections
      especially related to the colony-stimulating factors in which Australian
      involvement has been pre-eminent from discovery to clinical use. Nevertheless
      Australian scientists have also made profound contributions to other areas of
      cytokine and growth factor biology (including interferons, inflammatory
      cytokines, chemokines and epidermal, insulin-like and vascular endothelial growth
      factors) that are briefly described in this review as well as other chapters in
      this volume. 

PMID- 23548182
TI  - Attenuation of cognitive impairment by the nonbacteriolytic antibiotic daptomycin
      in Wistar rats submitted to pneumococcal meningitis.
AB  - BACKGROUND: Streptococcus pneumoniae is associated with neurologic sequels, such
      as, seizures, sensory-motor deficits, hearing loss, learning and memory
      impairment, which can occur in approximately 30 to 52% of surviving patients.
      Neuronal damage can be caused by intense inflammatory reaction and direct effects
      of the bacteria virulence factors. The aim of the present study was to evaluate
      the effects of the nonbacteriolytic antibiotic daptomycin versus ceftriaxone on
      behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis.
      RESULTS: Ten days after induction we verified that the meningitis group with
      daptomycin treatment showed retention of aversive memory; it presented memory of
      the object recognition at short term and long term. In continuous multiple-trials
      step-down inhibitory avoidance task the meningitis group with ceftriaxone
      treatment required approximately two times more stimulus to reach the acquisition
      criterion when compared with meningitis group with daptomycin treatment. However,
      in the habituation memory test there were no differences in the number of
      crossings and rearings in training and task sessions demonstrating habituation
      impairment to the environment task in both meningitis groups. CONCLUSIONS: The
      evidence of the present study shows the potential alternative of the treatment
      with daptomycin in preventing learning and memory impairments caused by
      pneumococcal meningitis. Further investigations are necessary to provide support
      for evaluation of daptomycin as an alternative treatment of bacterial meningitis.

PMID- 23548183
TI  - Dynamic metabolic modeling of a microaerobic yeast co-culture: predicting and
      optimizing ethanol production from glucose/xylose mixtures.
AB  - BACKGROUND: A key step in any process that converts lignocellulose to biofuels is
      the efficient fermentation of both hexose and pentose sugars. The co-culture of
      respiratory-deficient Saccharomyces cerevisiae and wild-type Scheffersomyces
      stipitis has been identified as a promising system for microaerobic ethanol
      production because S. cerevisiae only consumes glucose while S. stipitis
      efficiently converts xylose to ethanol. RESULTS: To better predict how these two
      yeasts behave in batch co-culture and to optimize system performance, a dynamic
      flux balance model describing co-culture metabolism was developed from genome
      scale metabolic reconstructions of the individual organisms. First a dynamic
      model was developed for each organism by estimating substrate uptake kinetic
      parameters from batch pure culture data and evaluating model extensibility to
      different microaerobic growth conditions. The co-culture model was constructed by
      combining the two individual models assuming a cellular objective of total growth
      rate maximization. To obtain accurate predictions of batch co-culture data
      collected at different microaerobic conditions, the S. cerevisiae maximum glucose
      uptake rate was reduced from its pure culture value to account for more efficient
      S. stipitis glucose uptake in co-culture. The dynamic co-culture model was used
      to predict the inoculum concentration and aeration level that maximized batch
      ethanol productivity. The model predictions were validated with batch co-culture
      experiments performed at the optimal conditions. Furthermore, the dynamic model
      was used to predict how engineered improvements to the S. stipitis xylose
      transport system could improve co-culture ethanol production. CONCLUSIONS: These
      results demonstrate the utility of the dynamic co-culture metabolic model for
      guiding process and metabolic engineering efforts aimed at increasing
      microaerobic ethanol production from glucose/xylose mixtures.

PMID- 23548184
TI  - [Cushing's syndrome during HIV treatment: pharmacological interaction during use
      of ritonavir].
AB  - Physicians are not always aware that locally administered glucocorticoids can
      cause systemic toxicity. This risk is greatly enhanced in the case of
      pharmacological interactions. We present two cases of HIV-infected patients who
      developed Cushing-like symptoms as a result of a pharmacological interaction.
      Their antiretroviral treatment regimen consisted of atazanavir, ritonavir,
      tenofovir and emtricitabine. One patient received salmeterol/fluticasone
      inhalations for asthmatic bronchitis. The other was treated with intra-articular
      triamcinolonacetonide injections for ongoing shoulder complaints. Ritonavir
      exhibits strong inhibition of hepatic enzyme CYP 3A4, which is part of the major
      metabolic pathway of most glucocorticoids. As a result of this interaction even
      locally administered glucocorticoids can cause symptoms of overdose, e.g. Cushing
      like symptoms. Beclomethasone is a safe alternative for inhaled glucocorticoids
      as it is not metabolized by CYP 3A4. There is no substitute for intra-articular
      administration of triamcinolonacetonide. Depending on necessity of the
      administration of the drug, changing ritonavir-containing antiretroviral therapy
      to a non-interacting compound, e.g., an integrase inhibitor, is an option.

PMID- 23548185
TI  - [Low health literacy in ethnic minority patients: understandable language is the
      beginning of good healthcare].
AB  - In order to provide adequate healthcare to ethnic minority patients, healthcare
      professionals must use professional interpreter services to effectively overcome
      language barriers. Many ethnic minority patients have low health literacy, i.e.
      they have difficulty obtaining, understanding and implementing health
      information. They therefore have a higher risk of poorer health outcomes. Health
      care professionals need to adapt their communication to patients with low health
      literacy by checking whether the patient has understood them, avoiding use of
      medical jargon and tailoring information to the patient's perspective. Various
      practical strategies have been developed to support health care professionals to
      communicate effectively with patients with low health literacy. Scientific
      research is needed to investigate the effectiveness of such strategies in various
      populations and to systematically develop, implement and evaluate new strategies.

PMID- 23548186
TI  - [Depressive disorders in ethnic minorities in the doctor's office].
AB  - Doctors often find the diagnosis and treatment of psychiatric disorders in non
      Western ethnic minorities difficult. Not only do language and culture form
      barriers to understanding, the symptoms of these disorders can be expressed in
      unfamiliar ways. We describe three cases that illustrate how the clinical
      presentation of depression in ethnic minorities living in the Netherlands can
      differ from that of Dutch patients. While the core symptoms of depressive
      disorder are similar, ethnic minority patients exhibit somatic symptoms more
      frequently. On average, they also have more severe symptoms, more psychiatric
      comorbidity such as anxiety and psychosis; the illness is also more often
      complicated by a multitude of social problems. Improving the diagnosis and
      treatment of depression in ethnic minorities requires knowledge and the
      exploration of potential differences in symptom presentation and the patient's
      explanatory models of mental illness. Patients and physicians also need to
      discuss their mutual expectations, in order to reach a consensus about treatment
      goals.

PMID- 23548188
TI  - [Every physician should know how to take an occupational history: the importance
      of teaching occupational medicine in medical school].
AB  - Working and participating in society are important for one's health and
      wellbeing. This also works the other way around: in order to work or participate,
      one has to be healthy. Every doctor should learn about this reciprocal
      relationship during their medical training. In a survey undertaken by the
      Netherlands Society of Occupational Medicine, the amount of time spent on
      occupational medicine in the curriculum of eight Dutch medical faculties was
      examined. The study showed vast differences between faculties in the amount of
      time spent on occupational medicine, in the learning methods employed and also in
      the number of students who participate in internships. The situation in the
      Netherlands compares favourably with that in other European countries. Sufficient
      specific attention to subjects related to health and work during undergraduate
      education is important for all doctors and a prerequisite to increase the number
      of medical students who subsequently choose a career in occupational health
      medicine.

PMID- 23548189
TI  - [Laparoscopic evaluation of the appendix].
AB  - In the Netherlands every year about 16,000 appendectomies are carried out.
      Despite the increase in preoperative radiological evaluation of the appendix, the
      negative appendectomy rate is still around 16%, with a morbidity of approximately
      5%. The Dutch practice guideline on appendicitis states that a normal appendix
      should not be removed, although laparoscopic criteria to establish appendicitis
      are lacking. Retrospective analysis of negative appendectomies shows that in 51%
      of cases the surgeon was convinced the appendix was inflamed. Furthermore, in an
      online survey, 78% of responding Dutch surgeons stated that if good and
      reproducible criteria for identifying appendicitis during laparoscopy were
      available they would use them. In conclusion, laparoscopic evaluation of the
      appendix is not always easy and use of the laparoscopic appendicitis score (LAPP)
      might lead to fewer negative appendectomies with their associated morbidity.
      Surgeons should be more aware of the morbidity associated with a negative
      appendectomy.

PMID- 23548190
TI  - [The development of cataract surgery after 1745].
AB  - Nowadays, cataract surgery is the most commonly performed surgical procedure in
      the Netherlands. This is due to the increasing incidence of cataracts, the
      changing indication for surgery in our society where good vision is becoming
      increasingly important, and the quality of the operation. How was this modern
      procedure developed? Cataracts were treated by couching until the middle of the
      18th century. Since then, many discoveries by a number of doctors changed the
      procedure gradually from couching to lens extraction and through extracapsular to
      intracapsular extraction with the simultaneous implantation of an intraocular
      lens. This article outlines the development and also discusses some of the many
      inventions in the field of instrumentation and materials that have brought this
      intervention to its current high level; these include the cryo-probe,
      implantation of artificial lenses, the use of hyaluronic acid, phaco
      emulsification, smaller incisions without sutures and the development of foldable
      intraocular lenses.

PMID- 23548191
TI  - [Catheter ablation in patients with atrial fibrillation: what will change in
      daily practice?].
AB  - A recent publication compared catheter ablation and antiarrhythmic drugs as
      initial therapy for paroxysmal atrial fibrillation. No difference was seen in the
      primary endpoint of the cumulative AF burden over two years. The burden of AF was
      documented objectively by a series of 7-day continuous ECG recordings; a method
      that will evolve as a gold standard for measuring the AF burden. The major
      shortcoming of the study was an obsolete ablation endpoint, lacking verification
      of pulmonary vein isolation. Other drawbacks were the fact that ablations were
      not exclusively carried out in high-volume centres and a high cross-over rate in
      the drug group. Also, although the primary endpoint was not significantly
      different, several secondary outcomes obviously favoured ablation. Outcomes in
      both the ablation and drug groups were relatively good, and this study will not
      change the current practice for the majority of paroxysmal AF patients, although
      catheter ablation could be performed as the initial therapy.

PMID- 23548192
TI  - [Osteoarthritis of the knee: lose weight first?].
AB  - Being heavy and having knee pain often co-exists. To date, the optimal treatment
      for patients with osteoarthritis of the knee and obesity remains the subject of
      debate, since patients with a high BMI (> 30 kg/m2) have a higher risk of
      complications following total knee arthroplasty (TKA). Kerkhoffs and colleagues
      suggest that these patients should first be submitted to a weight-loss programme
      prior to their TKA to reduce the risk of complications. This commentary addresses
      various questions arising from the Dutch meta-analysis by Kerkhoffs. For
      instance, should patients who fail to lose weight still undergo TKA or have
      bariatric surgery, or are there other options? Finally, suggestions are made for
      future research that might shed light upon this critical issue.

PMID- 23548193
TI  - [A woman with a painful swelling of the upper arm].
AB  - A 81-year-old woman presented at the emergency department with a painful right
      arm due to a comminuted fracture of the humeral head. Operation was postponed
      because of a wound and vulnerable skin due to a large hematoma. By the time of
      the operation, the humeral head had migrated subcutaneously which resulted in a
      solid swelling of the upper arm.

PMID- 23548194
TI  - [Graphic images on cigarette packages not effective].
AB  - The Dutch Government intends to make graphic images on cigarette packages
      mandatory. However, contrary to other policy measures to reduce smoking, health
      warnings do not work. There is no acceptable evidence in favour of graphic images
      and behaviour change theories suggest methods of change that improve skills, self
      efficacy and social support. Thus, theory- and evidence-based policy should focus
      on prohibiting the tobacco industry from glamourizing packaging and make health
      communications on packages mandatory. As to the type of communications to be
      used, theory and evidence suggest that warning of the negative consequences of
      smoking is not an effective approach. Rather, targeting the most important
      determinants of the initiation of smoking and its successful cessation - such as
      skills, self-efficacy and subjective norm - along with the most effective
      behaviour change methods appears to be the most expedient strategy.

PMID- 23548196
TI  - Rethinking future development of molecular therapies in hepatocellular carcinoma:
      a bottom-up approach.
AB  - The high failure rate of phase 3 trials in oncology is forcing the scientific
      community to rethink drug development strategies and optimize trial design. The
      current paradigm of systemic therapies is progressively favoring molecular-based
      patient selection. In hepatocellular carcinoma, four out of the five phase 3
      trials that tested molecular therapies in the last 5 years have been negative.
      None of them included enriched populations using predicted biomarkers of
      response. Hence, there is an increasing need to provide new targets and refine
      selection criteria in HCC clinical trials using molecular readouts of tumor
      biology.

PMID- 23548195
TI  - Effects of nurse-led motivational interviewing of patients with chronic
      musculoskeletal pain in preparation of rehabilitation treatment (PREPARE) on
      societal participation, attendance level, and cost-effectiveness: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Non-adherence and drop-out are major problems in pain rehabilitation.
      For patients with various health problems, motivational interviewing (MI) has
      shown promising effects to tackle these problems. In chronic pain patients, the
      effectiveness of MI is however unknown. Therefore, a MI-based pre-pain
      rehabilitation intervention (MIP) addressing motivation, expectations, and
      beliefs has been developed to prepare eligible patients for rehabilitation
      treatment. METHODS/DESIGN:  STUDY DESIGN: A parallel randomized controlled trial
      including two interventions: a motivational interviewing pre-pain rehabilitation
      intervention (MIP) and a usual care (UC) control arm. Follow-up will be 6 months
      after completion of rehabilitation treatment. STUDY POPULATION: One hundred and
      sixty (n = 80 per arm) patients with chronic non-specific musculoskeletal pain
      visiting an outpatient rehabilitation department, who are eligible to participate
      in an outpatient cognitive behavioral pain rehabilitation program. INTERVENTION:
      MIP consists of two sessions to prepare and motivate the patient for pain
      rehabilitation treatment and its bio psychosocial approach. UC consists of
      information and education about the etiology and the general rehabilitation
      approach of chronic pain. Both the MIP and UC contain two sessions of 45 to 60
      minutes each. OBJECTIVE: The aim of the current study is to evaluate the
      effectiveness of MIP compared to UC in terms of an increase in the long-term
      level of societal participation and decrease of drop-out during rehabilitation
      treatment.Main study endpoints: Primary outcome is the change in level of
      participation (according to the ICF-definition: 'involvement in a life
      situation') 6 months after completion of rehabilitation treatment. Secondary
      outcomes are adherence and treatment drop-out, disability, pain intensity, self
      reported main complaints, (pain-specific) self-efficacy, motivation, and quality
      of life. Costs are calculated including the costs of the pre-treatment
      intervention, productivity losses, and healthcare utilization. Potential
      moderators and active ingredients of MI are explored. For the process evaluation,
      parameters such as MI fidelity, feasibility, and experiences are explored.
      DISCUSSION: The results of this study will provide evidence on the effectiveness
      of this MI-based pre-treatment in pain rehabilitation. Furthermore, a cost
      effectiveness analysis and exploration of moderating and working mechanisms of MI
      and an extensive process evaluation takes place. TRIAL REGISTRATION: Nederlands
      trial register NTR3065.

PMID- 23548197
TI  - Established and new-generation antithrombotic drugs in patients with cirrhosis -
      possibilities and caveats.
AB  - Until recently, it was widely accepted that patients with cirrhosis have a
      bleeding tendency related to the changes in the hemostatic system that occur as a
      consequence of the disease. However, it has now been well established that
      patients with cirrhosis are at risk for both bleeding and thrombotic
      complications. These thrombotic complications include portal vein thrombosis,
      deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular
      infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in
      patients with cirrhosis have been used only minimally in the past due to the
      perceived bleeding risk. As the thrombotic complications and the necessity of
      antithrombotic treatment in these patients are increasingly recognized, the use
      of antithrombotic drugs in this population is likely increasing. Moreover, given
      the rising incidence of fatty liver disease and generally longer survival times
      of patients with chronic liver diseases, it would be reasonable to presume that
      some of these thrombotic complications may be increasing in incidence over time.
      In this review, we will outline the indications for antithrombotic treatment in
      patients with cirrhosis. Furthermore, we will discuss the available
      antithrombotic drugs and indicate possible applications, advantages, and caveats.
      Since for many of these drugs very little experience in patients with cirrhosis
      exists, these data are essential in the design of future clinical and laboratory
      studies on mechanisms, efficacy, and safety of the various antithrombotic
      strategies in these patients. 

PMID- 23548198
TI  - Imaging of hepatitis C virus infection in liver grafts after liver
      transplantation.
AB  - BACKGROUND & AIMS: The detection of native hepatitis C virus (HCV) antigens in
      liver tissue may be relevant to diagnostic purposes and to better understand the
      pathogenesis of HCV infection. The aim of our study was to characterize HCV
      antigens in liver grafts. METHODS: We selected 32 liver transplant (LT)
      recipients with recurrent hepatitis C. HCV core and NS5A antigens were detected
      in formalin-fixed, paraffin-embedded (FFPE) liver biopsies obtained immediately
      after graft reperfusion (negative controls), during the acute phase of HCV
      infection (1-6 months) and during follow-up (7-74 months) after LT. Viral
      antigens were assessed by immunohistochemistry and confocal microscopy. RESULTS:
      All reperfusion biopsies were negative for both antigens. Core protein was
      detected in 75% and 33% of acute phase and follow-up biopsies, respectively. HCV
      antigens were not detected in any of the 10 samples from patients who cleared HCV
      after antiviral treatment. Immunostaining was hepatocellular, with a granular
      cytoplasmic pattern and a wide spectrum of intensity. We found a significant
      association between viral load and the presence of HCV core-positive hepatocytes
      (p=0.004). NS5A colocalized strongly with core (66%) and adipophilin (36%),
      supporting the localization of core and NS5A around lipid droplets. A detailed
      three-dimensional analysis showed that NS5A surrounded the core and adipophilin
      positive areas. CONCLUSIONS: HCV antigens can be detected in FFPE liver biopsies
      by immunohistochemistry. The in vivo colocalization of core and NS5A proteins
      around the lipid droplets supports that the latter may play a role in virus
      particle production, similar to what reported in vitro.

PMID- 23548199
TI  - The association between lifting an administrative restriction on antidepressant
      dispensing and treatment patterns in Iceland.
AB  - PURPOSE: On March 1st 2009, restrictions on the dispensing of selective serotonin
      reuptake inhibitors (SSRI) in Iceland were lifted. Incident rates and changes in
      early discontinuation and switching before and after the change were
      investigated. METHODS: New users of antidepressants between March 1st 2006 and
      March 1st 2010 were selected from the Icelandic Prescriptions Database. The study
      population was split into one intervention cohort (2009) and three comparison
      cohorts (2006, 2007, and 2008). Incidence rate ratios (IRR) and odds ratios (OR)
      were used to compare incidence rates and early discontinuation. RESULTS: The
      overall incidence rates of antidepressant use decreased from 33.10 to 28.71 per
      1000 persons per year (IRR 0.87; 95% confidence interval (CI), 0.78-0.97) from
      the 2006 to the 2009 cohort. The incidence rate for SSRIs did not change over the
      period. Early discontinuation for SSRIs increased from 30.2% in 2006 to 34.1% in
      2009 (OR 1.19; 95% CI 1.06-1.33). CONCLUSIONS: The change in reimbursement does
      not seem to have affected incidence rates but it may be related to increased
      early discontinuation, which can lead to increased drug wastage. It might be more
      clinically rational to initiate patients on smaller supply, allowing for more
      frequent check-up visits.

PMID- 23548200
TI  - RBANS cluster profiles in a geriatric community-dwelling sample.
AB  - Neuropsychological heterogeneity is prevalent in geriatric individuals and is due
      to a number of factors including the onset of neuropathology, increased risk of
      emotional complications, and normal cognitive changes associated with aging. In
      order to better characterize normal neurocognitive variability in this
      population, cluster analysis was used on a sample of 699 community-dwelling
      geriatric patients who completed The Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS). Three-, four-, five-, and six-cluster
      solutions were examined and based on a number of criteria, the four-cluster
      solution was selected for further analysis. Clusters were defined primarily by
      measures of immediate memory, delayed memory, and processing speed, and differed
      on self-reported measures of functioning. These findings provide insights on
      normal neuropsychological variation in community-dwelling geriatric individuals. 

PMID- 23548201
TI  - Human exposure assessment of indoor dust: importance of particle size and spatial
      position.

PMID- 23548202
TI  - Formation of a tyrosine adduct involved in lignin degradation by Trametopsis
      cervina lignin peroxidase: a novel peroxidase activation mechanism.
AB  - LiP (lignin peroxidase) from Trametopsis cervina has an exposed catalytic
      tyrosine residue (Tyr181) instead of the tryptophan conserved in other lignin
      degrading peroxidases. Pristine LiP showed a lag period in VA (veratryl alcohol)
      oxidation. However, VA-LiP (LiP after treatment with H2O2 and VA) lacked this
      lag, and H2O2-LiP (H2O2-treated LiP) was inactive. MS analyses revealed that VA
      LiP includes one VA molecule covalently bound to the side chain of Tyr181,
      whereas H2O2-LiP contains a hydroxylated Tyr181. No adduct is formed in the Y171N
      variant. Molecular docking showed that VA binding is favoured by sandwich pi
      stacking with Tyr181 and Phe89. EPR spectroscopy after peroxide activation of the
      pre-treated LiPs showed protein radicals other than the tyrosine radical found in
      pristine LiP, which were assigned to a tyrosine-VA adduct radical in VA-LiP and a
      dihydroxyphenyalanine radical in H2O2-LiP. Both radicals are able to oxidize
      large low-redox-potential substrates, but H2O2-LiP is unable to oxidize high
      redox-potential substrates. Transient-state kinetics showed that the tyrosine-VA
      adduct strongly promotes (>100-fold) substrate oxidation by compound II, the rate
      limiting step in catalysis. The novel activation mechanism is involved in
      ligninolysis, as demonstrated using lignin model substrates. The present paper is
      the first report on autocatalytic modification, resulting in functional
      alteration, among class II peroxidases.

PMID- 23548204
TI  - Towards black-box calculations of tunneling splittings obtained from vibrational
      structure methods based on normal coordinates.
AB  - Multidimensional potential energy surfaces obtained from explicitly correlated
      coupled-cluster calculations and further corrections for high-order correlation
      contributions, scalar relativistic effects and core-correlation energy
      contributions were generated in a fully automated fashion for the double-minimum
      benchmark systems OH3(+) and NH3. The black-box generation of the potentials is
      based on normal coordinates, which were used in the underlying multimode
      expansions of the potentials and the MU-tensor within the Watson operator. Normal
      coordinates are not the optimal choice for describing double-minimum potentials
      and the question remains if they can be used for accurate calculations at all.
      However, their unique definition is an appealing feature, which removes remaining
      errors in truncated potential expansions arising from different choices of
      curvilinear coordinate systems. Fully automated calculations are presented, which
      demonstrate, that the proposed scheme allows for the determination of energy
      levels and tunneling splittings as a routine application. 

PMID- 23548203
TI  - Genome-wide association studies identify several new loci associated with
      pigmentation traits and skin cancer risk in European Americans.
AB  - Aiming to identify novel genetic loci for pigmentation and skin cancer, we
      conducted a series of genome-wide association studies on hair color, eye color,
      number of sunburns, tanning ability and number of non-melanoma skin cancers
      (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European
      Americans in the replication stage (for eye color, 3871 males in the discovery
      stage and 2496 males in the replication stage). We targeted novel chromosome
      regions besides the known ones for replication. As a result, we identified a new
      region downstream of the EDNRB gene on 13q22 associated with hair color and the
      strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P =
      2.4 * 10(-14); P = 5.4 * 10(-9) in the discovery set and P = 1.2 * 10(-6) in the
      replication set). Using blue, intermediate (including green) and brown eye colors
      as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3
      associated with brown eye (P = 7.0 * 10(-8); P = 5.3 * 10(-5) in the discovery
      set and P = 0.02 in the replication set). Additionally, we identified a
      significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2
      gene region on brown eye color (P-value for interaction = 3.8 * 10(-3)). As for
      the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on
      chromosome 14: rs12203592 in IRF4 (P = 7.2 * 10(-14); P = 1.8 * 10(-8) in the
      discovery set and P = 6.7 * 10(-7) in the replication set), rs12202284 between
      IRF4 and EXOC2 (P = 5.0 * 10(-8); P = 6.6 * 10(-7) in the discovery set and P =
      3.0 * 10(-3) in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 *
      10(-8); P = 5.3 * 10(-7) in the discovery set and P = 0.01 in the replication
      set). 

PMID- 23548205
TI  - Limited perturbation of a DPPC bilayer by fluorescent lipid probes: a molecular
      dynamics study.
AB  - The properties of lipid bilayer nanometer-scale domains could be crucial for
      understanding cell membranes. Fluorescent probes are often used to study
      bilayers, yet their effects on host lipids are not well understood. We used
      molecular dynamics simulations to investigate perturbations in a fluid DPPC
      bilayer upon incorporation of three indocarbocyanine probes: DiI-C18:0, DiI
      C18:2, or DiI-C12:0. We find a 10-12% decrease in chain order for DPPC in the
      solvation shell nearest the probe but smaller effects in subsequent shells,
      indicating that the probes significantly alter only their local environment. We
      also observe order perturbations of lipids directly across from the probe in the
      opposite leaflet. Additionally, the DPPC headgroup phosphorus-to-nitrogen vector
      of lipids nearest the probe exhibits preferential orientation pointing away from
      the DiI. We show that, while DiI probes perturb their local environment, they do
      not strongly influence the average properties of "nanoscopic" domains containing
      a few hundred lipids.

PMID- 23548206
TI  - Strong cation exchange-type chiral stationary phase for enantioseparation of
      chiral amines in subcritical fluid chromatography.
AB  - A new strong cation exchange type chiral stationary phase (SCX CSP) based on a
      syringic acid amide derivative of trans-(R, R)-2-aminocyclohexanesulfonic acid
      was applied to subcritical fluid chromatography (SFC) for separation of various
      chiral basic drugs and their analogues. Mobile phase systems consisting of
      aliphatic alcohols as polar modifiers and a broad range of amines with different
      substitution patterns and lipophilicity were employed to evaluate the impact on
      the SFC retention and selectivity characteristics. The observed results point to
      the existence of carbonic and carbamic acid salts formed as a consequence of
      reactions occurring between carbon dioxide, the alcoholic modifiers and the amine
      species present in the sub/supercritical fluid medium, respectively. Evidence is
      provided that these species are essential for affecting ion exchange between the
      strongly acidic chiral selector units and the basic analytes, following the well
      established stoichiometric displacement mechanisms. Specific trends were observed
      when different types of amines were used as basic additives. While ammonia gave
      rise to the formation of the most strongly eluting carbonic and carbamic salt
      species, simple tertiary amines consistently provided superior levels of
      enantioselectivity. Furthermore, trends in the chiral SFC separation
      characteristics were investigated by the systematic variation of the modifier
      content and temperature. Different effects of additives are interpreted in terms
      of changes in the relative concentration of the transient ionic species
      contributing to analyte elution, with ammonia-derived carbamic salts being
      depleted at elevated temperatures by decomposition. Additionally, in an effort to
      optimize SFC enantiomer separation conditions for selected analytes, the impact
      of the type of the organic modifier, temperature, flow rate and active back
      pressure were also investigated.

PMID- 23548207
TI  - "Dilute & shoot" approach for rapid determination of trace amounts of nicotine in
      zero-level e-liquids by reversed phase liquid chromatography and hydrophilic
      interactions liquid chromatography coupled with tandem mass spectrometry
      electrospray ionization.
AB  - Two analytical procedures are proposed where HILIC and RPLC techniques are
      coupled with tandem mass spectrometry detection for rapid determination of trace
      amounts of nicotine in zero-level liquids for electronic cigarettes. Samples are
      prepared on the basis of the approach "dilute & shoot" which makes this important
      step quick and not complicated. The chromatographic separation was carried out on
      a Zorbax XDB column (RPLC method) and Ascentis Si column (HILIC mode). Within-run
      precisions (CVs) measured at three concentration levels were as follows: 0.73%,
      0.98% and 1.44% for RPLC method and 1.39%, 1.44% and 0.57% (HILIC mode). Between
      run CVs were as follows: 1.94%, 1.02% and 1.22% for RPLC mode and 1.49%, 1.20%
      and 1.22% for HILIC mode. The detection limits of RPLC and HILIC modes were 4.08
      and 3.90 ng/mL respectively. The proposed procedures are rapid, not complicated,
      sensitive and are suitable for fast determination of trace amounts of nicotine in
      zero-level liquids for electronic cigarettes.

PMID- 23548208
TI  - Comedo-DCIS is a precursor lesion for basal-like breast carcinoma: identification
      of a novel p63/Her2/neu expressing subgroup.
AB  - Basal breast cancer comprises ~15% of invasive ductal breast cancers, and
      presents as high-grade lesions with aggressive clinical behavior. Basal breast
      carcinomas express p63 and cytokeratin 5 (CK5) antigens characteristic of the
      myoepithelial lineage, and typically lack Her2/neu and hormone receptor
      expression. However, there is limited data about the precursor lesions from which
      they emerge. Here we wished to determine whether comedo-ductal carcinoma in situ
      (comedo- DCIS), a high-risk in situ breast lesion, serve as precursors for basal
      like breast cancer. To determine this link, p63, CK5, Her2/neu, epidermal growth
      factor receptor (EGFR), estrogen receptor (ER) and progesterone receptor (PgR)
      expression were analyzed by immunohistochemistry in 17 clinical comedo- and 12
      noncomedo-DCIS cases, and in tumors derived from unfractionated and CK5
      overexpressing subpopulation (MCF10DCIS.com-CK5(high)) of MCF10DCIS.com cells, a
      model representative of clinical comedo-DCIS. p63 and Her2/neu coexpression was
      analyzed by immunofluorescence double labeling. A novel p63/CK5/Her2/neu
      expressing subpopulation of cells that are ER-/PgR-/EGFR- were identified in the
      myoepithelial and luminal areas of clinical comedo-DCIS and tumors derived from
      unfractionated MCF10DCIS.com and MCF10DCIS.com-CK5(high) cells. These data
      suggest that p63 and Her2/neu expressors may share a common precursor
      intermediate. P63, but not Her2/neu, expression was significantly associated (P =
      0.038) with microinvasion/recurrence of clinical comedo-DCIS, and simultaneous
      expression of p63 and Her2/neu was marginally associated (P = 0.067) with comedo
      DCIS. These data suggest that p63/Her2/neu expressing precursor intermediate in
      comedo-DCIS may provide a cellular basis for emergence of p63+/Her2/neu- or
      p63+/Her2/neu+ basal-like breast cancer, and that p63/Her2/neu coexpression may
      serve as biomarkers for identification of this subgroup of basal-like breast
      cancers.

PMID- 23548209
TI  - Association of calcium, phosphate and parathyroid hormone with renal allograft
      function: a retrospective cohort study.
AB  - BACKGROUND: Significant variations in postoperative levels of parathyroid hormone
      (PTH), calcium and phosphate exist after renal transplantation, but whether they
      affect allograft function is unknown. We investigated the association between
      early post-transplant levels of PTH, calcium and phosphate and graft function.
      METHODS: We performed a single-centre cohort study of renal transplant recipients
      from Addenbrooke's Hospital, Cambridge, between April 1997 and March 2007,
      evaluating the association between plasma calcium, phosphate and PTH 1 month
      after transplantation and change in epidermal growth factor receptor (eGFR) in
      the first 12 months after transplantation (estimated using the Modification of
      Diet in Renal Disease Study equation). Differences in eGFR between 26 and 52
      weeks after transplantation were computed using mixed effects linear regression
      models for repeated measures of eGFR, while adjusting for sociodemographic and
      biochemical variables. RESULTS: Three hundred and forty-three patients were
      eligible for study. The mean age (standard deviation) at transplant was 43 years
      (13 years). Between 30 and 90 days after transplantation, the median (25th-75th
      percentile) eGFR was 33 (26-50) ml/min/1.73 m(2), the mean calcium level was 2.4
      (0.17) mmol/l and the mean phosphate level was 0.78 (0.23) mmol/l. There was a
      significant interaction between calcium and phosphate levels (p = 0.006). In
      patients with low levels of phosphate, higher levels of calcium were associated
      with declining eGFR over time. However, in patients with a high phosphate level,
      higher calcium was associated with improved eGFR. CONCLUSIONS: Higher serum
      calcium in patients with low serum phosphate after transplantation is associated
      with a decline in graft function during the first year after transplantation.
      Disorders of mineral metabolism after transplant may represent an important
      therapeutic target to preserve allograft function.

PMID- 23548210
TI  - A combination of ampicillin and aminoglycoside for early-onset neonatal sepsis.

PMID- 23548211
TI  - Female sexual dysfunction: definition, classification, and debates.
AB  - Sexual dysfunction refers to difficulties that occur during the sexual response
      cycle that prevent the individual from experiencing satisfaction from sexual
      activity. It is relatively difficult to estimate the prevalence of female sexual
      dysfunction (FSD), because the definition and diagnostic criteria are still
      controversial and under development. These difficulties reveal our insufficient
      understanding of the basis of FSD. This review was conducted in an effort to deal
      with this complicated clinical issue, by examining the most updated clinical
      criteria of FSD under the context of a redefined female sexual response model.

PMID- 23548212
TI  - Methodological considerations in the analysis of the therapeutic significance of
      lymphadenectomy in endometrial cancer.
AB  - There needs to be clarification on eligibility requirements and procedure
      standardization with regard to the therapeutic role of lymphadenectomy. If this
      is not done, consensus on the role of lymphadenectomy will not be reached.
      Although pelvic lymphadenectomy is not necessary for patients with low-risk Stage
      I endometrial cancer, it has been suggested that combined pelvic and para-aortic
      lymphadenectomy is useful for patients with intermediate-/high-risk endometrial
      cancer. Therefore, the therapeutic role of lymphadenectomy should be continuously
      evaluated. If such a study is planned, it should not include patients with low
      risk of nodal metastasis, and one experimental arm of the study should assess
      combined pelvic and para-aortic lymphadenectomy (fundamentally including the area
      above the inferior mesenteric artery and the renal vein). It is necessary to
      establish a pre-operative risk assessment for nodal metastasis and procedural
      classification of lymphadenectomy. Some pre-operative risk assessments for nodal
      metastasis have been proposed from Asian countries. The extent of the surgical
      field is defined as the pelvic area alone, or combined pelvic and para-aortic
      area. The thoroughness of removal can be split into removal of only suspicious
      nodes, selective dissection, or systematic dissection. Although randomized
      controlled trials provide the highest level of clinical evidence, special
      difficulties are presented in randomized surgical trials. Nonentry of surgeons is
      a threat to external validity. The role of observational studies, especially
      prospective cohort studies should be reconsidered when assessing the therapeutic
      significance of lymphadenectomy.

PMID- 23548213
TI  - The meridian system and mechanism of acupuncture--a comparative review. Part 2:
      mechanism of acupuncture analgesia.
AB  - In traditional Chinese medicine (TCM), pain is never merely a sign of discomfort.
      It is usually an integral part of a particular disease or physiological
      malfunction. Thus pain should not be treated in isolation since it will disappear
      as soon as its cause is identified and removed. Hence, in this Part 2 of a three
      part series, initially, clinical pathologies in modern medicine and TCM are
      compared. Then, the pain pathophysiologies of these two schools of thought are
      reviewed. In addition, certain unique features of acupuncture effects that any
      valid mechanism must account for are outlined. Finally, various mechanisms of
      acupuncture analgesia are reviewed. One plausible mechanism based on the meridian
      system of Part 1, i.e., the chaotic wave theory of fractal continuum in terms of
      the neurovascular network, is also proposed. It contends that the injury current
      due to acupuncture at an acupoint will trigger electromagnetic inductive effects
      so that the impedances of correlated neurovascular bundles are drastically
      changed. Two consequent scenarios are possible. (1) If the impedance of the
      meridian hugely mismatches with that of the brain after acupuncture, then the
      traveling wave of pain signal will be largely reflected back and only partially
      transmitted to the brain, hence pain relief can be achieved. (2) If the impedance
      of the meridian entirely matches that of the pain source after acupuncture, then
      the pain source would appear to be nonexistent to the brain, hence analgesia can
      be achieved. The former mechanism can be used to explain the relief for chronic
      pain and the latter one for acute pain. It is believed that the proposed
      mechanisms via match or mismatch of the impedances can explain how the
      acupuncture works not only in the treatment of pain, but also in various other
      therapies of Part 3.

PMID- 23548214
TI  - Development of a chip-based multiplexed immunoassay using liposomal nanovesicles
      and its application in the detection of pathogens causing female lower genital
      tract infections.
AB  - OBJECTIVE: Cervicovaginitis is a highly prevalent disease that is a burden on
      healthcare globally. Immediate and adequate treatment can eradicate the infection
      and block subsequent complications. The feasibility of achip-based multiplexed
      immunoassay using liposomal nanovesicles was tested. MATERIALS AND METHODS: A
      multiplexed immunoassay chip containing five antibodies for five pathogens
      (Chlamydia trachomatis, Escherichia coli, Neisseria gonorrhoeae, Streptococcus
      agalactiae, and Candida albicans) was established and tested. Four patients with
      spiking of candidiasis were enrolled. The difference between positive and
      negative readings was evaluated using the paired Student t test. RESULTS: The
      detection threshold of Candida in this microarray was 100,000 CFU/mL in a vaginal
      sample, and the time required for the whole procedure was 3 hours. The testing of
      the four patients showed 100% for both sensitivity and specificity. CONCLUSION:
      This microarray chip was a rapid, easy, inexpensive and sensitive tool for
      detecting female lower genital tract Candida infection in a one-time vaginal
      sampling process, although the data on the four other pathogens were still
      unavailable. A larger population study is encouraged to test the validity of this
      multiplexed immunoassay chip.

PMID- 23548215
TI  - Survival analysis of Stage IIA1 and IIA2 cervical cancer patients.
AB  - OBJECTIVE: The aim of this study was to assess the benefits of the 2009
      International Federation of Gynecology and Obstetrics (FIGO) staging system for
      survival of patients with Stage IIA1 and IIA2 cervical cancer (Cx Ca). MATERIALS
      AND METHODS: A study cohort of 51 patients with Stage IIA Cx Ca was
      retrospectively collected from the 2004-2009 hospital-based, long-form Cx Ca data
      registry at Mackay Memorial Hospital (Taipei, Taiwan). The survivorship and
      overall survival were compared between these two groups (Stages IIA1 and IIA2)
      using log-rank test. RESULTS: Thirty-six and 15 patients were classified into
      Stages IIA1 and IIA2, respectively. Stage IIA2 patients were younger than those
      with Stage IIA1 disease (mean age, 47.4 vs. 55.1 years, p = 0.008), but no
      significant difference was observed in confirmed pelvic lymph node status (21.4%
      vs. 38.5%, p = 0.280) between them. Although the 2-year and 5-year overall
      survival was better among Stage IIA1 patients, there was no significant
      difference in survival between Stage IIA1 and IIA2 groups (2-year, 90.6% vs.
      77.8%; 5-year, 86.3% vs. 51.9%, p = 0.218). CONCLUSION: Although there was a
      trend in survival difference between Stage IIA1 and IIA2 patients, the difference
      was not statistically significant. The revised FIGO 2009 staging system for Cx Ca
      defines a group of Stage IIA patients with bulky tumor (Stage IIA2) that are
      generally younger than Stage IIA1 patients. It is sensible to investigate an
      alternate or enhanced treatment scheme for Stage IIA2 patients. Ideally, the
      treatment scheme should prevent unnecessary radical surgery if a patient can be
      exposed to either chemotherapy or radiotherapy, alone or in combination.

PMID- 23548217
TI  - Using Akaike information criterion and minimum mean square error mode in
      compensating for ultrasonographic errors for estimation of fetal weight by new
      operators.
AB  - OBJECTIVES: The accuracy of ultrasound (US) measurements is operator dependent.
      In order to decrease the operator-dependent errors in estimated fetal weight
      (EFW), a model selection analysis was undertaken to select significant
      compensation weighting factors on ultrasonographic parameters to support
      artificial neural network (ANN), and thus to enhance the accuracy of fetal weight
      estimation. MATERIALS AND METHODS: In total, 2127 singletons were examined by
      prenatal US within 3 days before delivery for ANN development, and another 100
      cases were selected from new operators for evaluation. First, correlation
      analysis was used to analyze the differences between the prenatal and postnatal
      parameters. Second, Akaike information criterion (AIC) was used to determine the
      number of database partition and optimal weightings for compensating the input
      parameters of the ANN model. Finally, minimum mean squared error (MMSE) mode was
      utilized to determine the optimal EFW. RESULTS: EFW of the proposed compensation
      model using AIC and MMSE showed mean absolute percent error of 5.1 +/- 3.1% and
      mean absolute error of 158.9 +/- 96.2 g. When comparing the accuracy of EFW, our
      model using AIC and MMSE was superior to those conventional EFW formulas (all p <
      0.05). CONCLUSION: We proved that performing the parameter compensation (by AIC)
      and model compensations (by MMSE) for the ANN model can improve EFW accuracy. Our
      AIC-MMSE model of EFW will contribute to the improvement of accuracy when adding
      new US datasets measured by new operators.

PMID- 23548216
TI  - Reproductive performance of severely symptomatic women with uterine adenomyoma
      who wanted preservation of the uterus and underwent combined surgical-medical
      treatment.
AB  - OBJECTIVE: To assess the factors associated with future pregnancy and successful
      delivery in women who were treated for uterine adenomyoma with combination
      (surgical-medical) therapy using ultramini- or mini-laparotomy conservative
      surgery and gonadotropin-releasing hormone agonist. MATERIALS AND METHODS: One
      hundred and two women were evaluated. Items for analysis included: age, body mass
      index, and conception history; clinical symptoms of dysmenorrhea and menorrhagia;
      tumor location and preoperative serum level of cancer antigen 125 (CA125); the
      intraoperative findings of the weight of the removed tumor, and the uterine
      cavity opening. RESULTS: After excluding those patients using contraception or
      searching for an assisted reproductive technique, a total of 56 women were
      enrolled for analysis. Twenty-three (41.1%) women had 27 clinical pregnancies
      after 3 years of follow-up; 15 went on to deliver a healthy live-born child; two
      delivered preterm but healthy babies; seven had elective abortions; four had
      spontaneous abortions; and one had an ectopic pregnancy. The women who had a
      successful delivery during the 3-year follow-up after treatment tended to be
      younger, with a lower body mass index, lower baseline analgesic usage score, and
      lower preoperative serum level of CA125, be nulliparous, and with an adenoma in
      an anterior location. The linear regression model showed that age and baseline
      analgesic usage score were independent predictors of successful delivery and
      accounted for 56.5% of the total variance related to successful delivery.
      CONCLUSION: Age was an important factor associated with future successful
      delivery, therefore, caution should be taken in considering the maintenance of
      future fertility in older women treated with surgical-medical therapy.

PMID- 23548218
TI  - Safety and efficacy of unidirectional barbed suture in mini-laparotomy
      myomectomy.
AB  - OBJECTIVE: To estimate the safety and effectiveness of unidirectional knotless
      barbed suture compared to the traditional suture for repair of uterine wall
      defects through myomectomy via mini-laparotomy. MATERIALS AND METHODS: This was a
      prospective clinical study performed by a single surgeon in a medical center.
      Sixty-eight women with symptomatic myoma were enrolled. Their uterine wall
      defects were repaired either by unidirectional knotless barbed suture (Group A)
      or by traditional suture (Group B). The surgical time, intraoperative blood loss,
      and number of myomas in the two groups were analyzed by two-sample t test.
      RESULTS: Surgical time required from skin incision to complete closure was
      significantly lower in Group A than in Group B (50.2 +/- 16.49 vs. 69.1 +/- 25.33
      min) (p = 0.0008). The intraoperative blood loss was also lower in Group A (mean,
      260.9 mL; range, 20-850 mL) than in Group B (mean, 394.7 mL; range, 50-2200 mL)
      but not statistically significant. CONCLUSION: The unidirectional knotless barbed
      suture may facilitate the repair of uterine defects during mini-laparotomy
      myomectomy by significantly lowering operative time. It may also reduce the
      intraoperative blood loss.

PMID- 23548219
TI  - Effect of intraumbilical vein oxytocin injection on third stage of labor.
AB  - OBJECTIVE: Manual removal of placenta is performed in 1-3% of cases, and although
      it is a well-established and relatively safe procedure, it is not without
      complications. We carried out this study to determine whether intraumbilical vein
      oxytocin injection reduces the need for manual removal of placenta and shortens
      the third stage of labor, in comparison with placebo. MATERIALS AND METHODS: In
      this randomized clinical trial, 178 women with singleton pregnancy and normal
      delivery were studied in 1 year. Immediately after fetus delivery, oxytocin
      infusion (20 IU/L) was started in both groups. Moreover, 10 IU oxytocin and 1 mL
      normal saline were injected into the umbilical vein of women in the experimental
      and control groups, respectively. The duration of third-stage labor, need for
      manual delivery of placenta, and drug side effects were evaluated in both groups.
      With regard to the mean level of hemoglobin before and after delivery, the two
      groups were compared using the Levene test and independent t test, and other
      qualitative variables of the two groups were compared using the chi(2) test.
      RESULTS: The women who received intraumbilical vein oxytocin had a shorter third
      stage of labor as compared with the placebo group (4.24 +/- 3.27 min vs. 10.66 +/
      7.41) (p < 0.001) and there was less need for manual delivery of placenta in the
      experiment group (1.1% vs. 5.1%) (p = 0.024). CONCLUSION: It was concluded that
      intraumbilical vein administration of 10 IU (1 mL) oxytocin immediately after
      fetus delivery was clinically effective in shortening the third stage of labor.

PMID- 23548220
TI  - Longitudinal changes in bone mineral density of healthy elderly women in southern
      Taiwan.
AB  - OBJECTIVE: Longitudinal data on bone decline in ethnic Chinese elderly are
      sparse, especially in healthy, aged women. This study reviews the longitudinal
      change in bone mineral density (BMD) at the femoral neck, great trochanter, and
      Ward's triangle in healthy elderly Taiwanese women. MATERIALS AND METHODS: A
      prospective cohort study was conducted, with 1500 women aged >= 61 years. Fifty
      four were eligible for hip evaluation and 52 underwent examination for hip BMD.
      Two years later, 50 women had a follow-up BMD examination. Linear regression was
      performed between age and bone density. The paired t test was used for BMD
      changes between examinations. RESULTS: In the initial study, there was a negative
      relationship between BMD and age using liner regression at all three sites (p <
      0.05). Two years later, there was a significant decrease in BMD at all three
      sites (p < 0.01). In terms of age cohorts, both age groups showed a significant
      decrease in BMD at the three sites studied (p < 0.01). There was a peak loss of
      BMD as high as 2.74% annually at the Ward's triangle in those aged 61-70 years.
      CONCLUSION: Our findings indicate that BMD is negatively correlated to aging in
      the healthy female. The loss of BMD at the Ward's triangle in those aged 61-70
      years is faster than at other sites. Attention should be given to bone loss in
      ethnic Chinese females because their bone loss is more severe than that of
      Caucasians.

PMID- 23548221
TI  - Sertoli-Leydig cell tumors of the ovary: a Taiwanese Gynecologic Oncology Group
      study.
AB  - OBJECTIVE: To report the natural history and prognosis of the uncommon Sertoli
      Leydig cell tumor (SLCT) of the ovary. MATERIALS AND METHODS: A 20-year
      retrospective review was conducted by the Taiwanese Gynecologic Oncology Group
      (TGOG), including nine tertiary medical centers from different regions in Taiwan.
      The medical records for 40 cases of ovarian SLCT were collected. Pathology
      reviews were carried out by a panel of expert pathologists. RESULTS: After
      pathological review, 17 patients were subsequently excluded because the pathology
      slides were unavailable in five cases, and discrepant results from the initial
      diagnosis were found in 12 cases (34%). For the remaining 23 patients, the median
      age was 41 years. The most common symptom was irregular vaginal bleeding followed
      by an abdominal mass or amenorrhea. Most of the tumors were unilateral and
      confined to the right ovary, with an average size of 8.2 cm. Preoperative serum
      markers were available for 12 patients and were elevated for three patients. All
      patients underwent primary surgery. Six patients accepted adjuvant chemotherapy,
      and bleomycin, etoposide, and cisplatin were used in four of them. Clinical
      follow-up information was available in 21 patients with a median of 19 months.
      Eighty-two percent of patients were alive and free of disease up to the date of
      the last follow-up. Two patients died of the disease. CONCLUSION: This study
      demonstrates the extreme rarity of ovarian SLCT in Taiwan. Histological
      discordance between the diagnosis and central review proves the need for
      expertise review before treatment. For an improved understanding of the
      biological behavior and treatment strategy for this unique tumor, international
      collaboration is imperative.

PMID- 23548222
TI  - Association between maternal periodontal disease and preterm delivery and low
      birth weight.
AB  - OBJECTIVE: It has been suggested that periodontal disease is an important risk
      factor for preterm low birth weight (PLBW). The purpose of this study was to
      determine the association of maternal periodontitis with low birth weight (LBW)
      and preterm birth (PB). MATERIALS AND METHODS: Pregnant women (n = 211) aged 22
      40 years were enrolled while receiving prenatal care. Dental plaque, probing
      depth, bleeding on probing, and clinical attachment level were used as criteria
      to classify three groups: a healthy group (HG; n = 82), a gingivitis group (GG; n
      = 67), and a periodontitis group (PG; n = 62). At delivery, birth weight was
      recorded. RESULTS: Mean infant weight at delivery was 3084.9 g. The total
      incidence of preterm birth and LBW infants was 10.4% and 8.1%, respectively. The
      incidence of LBW infants was 4.2% for term and 40.9% for preterm gestations.
      Maternal height was not correlated with infant birth weight (p = 0.245).
      Significant differences in mean infant birth weight were observed among the HG,
      GG, and PG groups (p = 0.030). No significant relationship was found between
      periodontal disease and PB, but the association between periodontal disease and
      LBW was significant. CONCLUSION: After appropriately controlling for confounding
      variables, our results do not support the hypothesis of an association that was
      observed in previous studies of maternal periodontal disease and infant PB, but
      the association between periodontal disease and LBW is significant.

PMID- 23548223
TI  - Robot-assisted tubal reanastomosis: initial experience in a single institution.
AB  - OBJECTIVE: To assess surgical outcomes for robot-assisted tubal reanastomosis in
      a single institution. MATERIALS AND METHODS: Between March 2009 and January 2010,
      10 patients underwent robot-assisted tubal ligation reversal (TLR) with a da
      Vinci S surgical system. Patient demographic data, including operative times,
      operative and postoperative complications, hospital stay, conversion to
      laparotomy and pregnancy rates were recorded. RESULTS: Mean age and body mass
      index for the patients were 37.7 (35-42) years and 28.9 (23.9-36.3) kg/m(2),
      respectively. The mean console time was 102.5 min and the mean total operation
      time was 130.6 (102-164) min. The mean hospital stay was 1.2 (1-2) days. There
      were no significant intra-operative or early-postoperative complications. All
      surgeries were completed robotically with no conversion to laparotomy. There were
      seven subsequent pregnancies in the study participants, representing a pregnancy
      rate of 70%, of which five were intrauterine pregnancies, one was an ectopic
      pregnancy, and one was an abortus. CONCLUSION: Robot-assisted TLR is safe and
      feasible. This procedure may facilitate minimally invasive treatment for patients
      who want to regain their fertility without the aid of artificial reproductive
      techniques.

PMID- 23548224
TI  - Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and
      serous ovarian cancer in Taiwan.
AB  - OBJECTIVE: To compare the prognosis of patients with advanced-stage primary
      peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer
      (PSOC). MATERIALS AND METHODS: This was a retrospective case-control study and
      included two study groups: one with stage III/IV PSPC (n = 38) patients and the
      other with PSOC (n = 53) patients. Patients were matched for histologic subtype
      (serous tumor), tumor stage, tumor grade, residual disease at the end of
      debulking surgery (primary or interval), and age (+/-5 years). RESULTS: Mean age
      was significantly greater for patients with PSPC (63.03 +/- 11.88 years) than for
      patients with PSOC (55.92 +/- 12.56 years, p = 0.008). Optimal debulking surgery
      was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In
      addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with
      platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was
      significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p <
      0.001). Progression-free survival (PFS) was similar in the PSPC [median 12
      months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7
      months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC
      (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months,
      95% CI 69.7-85.2; p = 0.006, log-rank statistic). CONCLUSION: PFS was similar for
      advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older
      and have more high-grade tumors, OS was shorter for PSPC than for POSC patients.
      Thus, management of the two types of cancer should not differ.

PMID- 23548225
TI  - Long-term follow-up of severely symptomatic women with adenomyoma treated with
      combination therapy.
AB  - OBJECTIVE: The aim of our study was to assess the long-term efficacy of
      conservative surgery combined with gonadotropin-releasing hormone agonist therapy
      for uterine adenomyoma. MATERIALS AND METHODS: We carried out an uncontrolled
      descriptive study of 285 women who had symptomatic uterine adenomyoma. A total of
      186 women with pathologically proven adenomyoma underwent ultramini-laparoscopic
      adenomyomectomy and a 6-month course of goserelin acetate treatment, and were
      evaluated semi-annually during a follow-up period of at least 3 years. RESULTS:
      Patient scores for dysmenorrhea using a self-reported six-point verbal numeric
      rating scale significantly declined compared with the baseline assessment, from
      3.84 +/- 0.65 to 0.33 +/- 0.57, 0.52 +/- 0.86, and 0.88 +/- 1.29 at the end of
      the 1-, 2-, and 3-year follow-up visits, respectively (p < 0.001). Similar
      reductions were observed for analgesic usage scores. Menorrhagia scores
      significantly decreased compared with the baseline assessment, from 3.45 +/- 1.46
      to 0.42 +/- 0.59, 0.65 +/- 0.83, and 1.1 +/- 1.34 at the end of the 1-, 2-, and 3
      year follow-up visits, respectively (p < 0.001). CONCLUSION: Combination therapy
      for adenomyoma provides an effective treatment option for long-term symptom
      control and uterine preservation in severely symptomatic women for whom previous
      long-term drug therapy has failed or proven to be intolerable.

PMID- 23548226
TI  - Prenatal diagnosis of fetal congenital cystic adenomatoid malformation of the
      lung using three-dimensional ultrasound: comparison between the 20th and 21st
      centuries.
AB  - OBJECTIVE: Congenital cystic adenomatoid malformation of the lung (CCAML) is one
      of the most common lung lesions diagnosed prenatally. In order to compare the
      trends and improvements of prenatal diagnosis of CCAML, we herein retrospectively
      reviewed our cases of fetal CCAML detected by three-dimensional ultrasound (3-D
      US) between two centuries. MATERIALS AND METHODS: We reviewed our computer
      database of prenatal diagnosis of CCAML in National Cheng Kung University
      Hospital from October 1994 to November 2011. All of the fetuses were initially
      scanned by two-dimensional (2-D) US to locate the region-of-interest (ROI). Then,
      the 3-D probe was used to scan all of the ROI systematically and mechanically,
      and the images were stored in the laser discs for further 3-D visualization and
      reconstruction. To compare the characteristics at prenatal diagnosis of CCAML
      between the 20th and 21st centuries in our hospital, Chi-square tests were
      undertaken. A p value <0.05 was considered as statistically significant. RESULTS:
      In total, 58 fetuses with CCAML were depicted by 3-D US in utero (12 cases were
      diagnosed in the 20th century and 46 cases in the 21st century). The ranges of
      gestational age at prenatal diagnosis of CCAML by 3-D US in the 20th century were
      between 15 and 36 weeks (mean=24 weeks), and were between 16 and 31 weeks
      (mean=22 weeks) in the 21st century. Moreover, nine cases (75%) were diagnosed at
      the second trimester in the 20th century, whereas 44 cases (96%) were diagnosed
      at the second trimester in the 21st century. CONCLUSION: The advancement of 3-D
      US has remarkable advantages in adding novel visual depiction of a 3-D lesion of
      a 3-D fetus in 3-D US after reconstruction, and thus assists substantially in the
      prenatal diagnosis and genetic consultation of CCAML. Furthermore, the trend
      analysis in this series showed a significantly earlier gestational age at
      prenatal diagnosis of CCAML in the 21st century than that in the 20th century.

PMID- 23548227
TI  - Mosaic trisomy 12 at amniocentesis: prenatal diagnosis and molecular genetic
      analysis.
AB  - OBJECTIVE: This study is aimed at prenatal diagnosis of mosaic trisomy 12 and
      reviewing the literature. MATERIALS AND METHODS: A 34-year-old woman underwent
      amniocentesis at 17 weeks of gestation because of advanced maternal age.
      Cytogenetic analysis of cultured amniocytes revealed a karyotype of
      47,XX,+12[9]/46,XX[14]. She was referred to the hospital for genetic counseling.
      Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative
      genomic hybridization (aCGH), interphase fluorescence in situ hybridization
      (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were
      applied on uncultured amniocytes, and conventional cytogenetic analysis was
      applied on cultured amniocytes. RESULTS: The aCGH analysis on uncultured
      amniocytes revealed a small genomic gain in chromosome 12. Interphase FISH
      analysis on uncultured amniocytes using a 12q11-q12-specific probe of RP11-496H24
      (green spectrum) showed three green signals in 17.8% (8/45 cells) of uncultured
      amniocytes. QF-PCR analysis on uncultured amniocytes using chromosome 12-specific
      microsatellite markers excluded uniparental disomy 12. Cytogenetic analysis of
      cultured amniocytes revealed a karyotype of 47,XX,+12[5]/46,XX[25]. The parents
      decided to continue the pregnancy. A healthy 3270 g female baby was delivered at
      39 weeks of gestation, with no phenotypic abnormalities. Cytogenetic analysis of
      the cord blood revealed a karyotype of 46,XX in 40/40 cultured lymphocytes. The
      neonate was normal in growth and psychomotor development at 6 months of age.
      Interphase FISH analysis on uncultured urinary cells revealed 5% (1/20 cells)
      mosaicism for trisomy 12. CONCLUSION: Prenatal diagnosis of mosaic trisomy 12 at
      amniocentesis should alert a clinically significant aneuploidy. Interphase FISH
      and aCGH on uncultured amniocytes are useful for rapid confirmation of low-level
      trisomy 12 mosaicism at repeated amniocentesis.

PMID- 23548228
TI  - Prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta
      associated with unaffected parents and paternal gonadal mosaicism.
AB  - OBJECTIVE: To present the prenatal diagnosis of recurrent autosomal dominant
      osteogenesis imperfecta (OI) associated with unaffected parents and paternal
      gonadal mosaicism. MATERIALS AND METHODS: A 37-year-old woman was referred for
      genetic counseling at 18 weeks of gestation because of advanced maternal age and
      a family history of OI. The woman had a daughter who was affected with OI type
      III and carried an insertion frameshift mutation of c.4308_4309insA in exon 52 of
      the COL1A1 gene. The woman and her husband were non-consanguineous and healthy.
      Amniocentesis was performed at 18 weeks of gestation. RESULTS: Cytogenetic
      analysis revealed a karyotype of 46,XX. Molecular analysis of the amniocytes
      revealed a recurrent mutation of c.4308_4309insA in exon 52 of the COL1A1 gene.
      Mutational analysis of the family revealed no mutation of the COL1A1 gene in the
      parental bloods. However, mosaicism for the COL1A1 mutation was found in the
      paternal sperms. Level II ultrasound examination showed a curved right tibia, a
      narrow chest with irregular ribs and mild frontal bossing in the fetus. The
      parents decided to terminate the pregnancy, and a female fetus was delivered at
      23 weeks of gestation with curved long bones. CONCLUSION: Recurrent autosomal
      dominant OI may occur in the offspring of unaffected parents with parental
      gonadal mosaicism. Genetic counseling of recurrent autosomal dominant OI should
      include a thorough mutational analysis of the family members, and mutational
      analysis of the sperm may detect paternal gonadal mosaicism for the mutation.

PMID- 23548229
TI  - Fertility after "only B-Lynch" suture: a case report and literature review.
AB  - OBJECTIVE: A new fertility assessment after a B-Lynch suture without a
      concomitant uterine devascularization is proposed. CASE REPORT: The case of a 37
      year-old woman who experienced postpartum hemorrhage due to uterine atony during
      cesarean delivery of the previous pregnancy is reported. A B-Lynch brace suturing
      technique, not associated to any other hemostatic surgical procedure, was carried
      out. One year later and after an uncomplicated pregnancy of 39 weeks, the patient
      delivered a healthy infant by an elective cesarean section. Only omental
      adhesions were found on the anterior surface of the uterus as a consequence of
      the previous B-Lynch suture. CONCLUSION: The B-Lynch hemostatic surgical
      procedure, alone, does not seem to have a negative impact on fertility.
      Additional clinical evidences in a greater case-series of patients are needed to
      assess the value of the method for fertility preservation.

PMID- 23548230
TI  - Report of two cases of adenoid cystic carcinoma of Bartholin's gland and review
      of literature.
AB  - OBJECTIVE: Primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare
      gynecologic malignancy. We report two cases from primary treatment to recurrence
      and the adjuvant treatment. CASE REPORT: A woman aged 37 years presented with a
      mass on the right posterior labia minor and underwent right radical hemi
      vulvectomy and right-side inguino-femoral node dissection. Final pathology showed
      ACC arising from Bartholin's gland with positive margins. She received adjuvant
      external beam radiation to the pelvis, right vulva, and groin area. However,
      distal metastasis occurred 42 months after initial treatment and she eventually
      died of multiple metastases. Another woman aged 48 years presented with a mass on
      the right posterior labia with intermittent pain. She underwent right hemi
      vulvectomy and right inguino-femoral lymph node dissection only because pathology
      showed ACC of Bartholin's gland with negative surgical margins. Lung metastasis
      occurred 59 months after initial treatment. She took tamoxifen only and achieved
      stable disease status for 4 years. CONCLUSION: To date, about 70 cases have been
      reported. We treated our second patient with antiestrogen therapy for 4 years and
      achieved good quality of life and stable disease status. However, further study
      on hormone therapy for ACC of Bartholin's gland is needed.

PMID- 23548231
TI  - Pelvic retroperitoneal cyst during pregnancy.
AB  - OBJECTIVE: The diagnosis and treatment of adnexal mass during pregnancy is a
      major challenge for obstetricians. A rare case is reported of retroperitoneal
      cystic lesion during pregnancy. CASE REPORT: A 31-year-old woman was diagnosed
      with an adnexal cystic lesion at 8 weeks of gestation and underwent laparoscopic
      surgery at 14 weeks of gestation. During laparoscopic surgery, the bilateral
      ovaries and tubes were normal, but the lesion was located on the right-side
      retroperitoneal area. Aspiration and enucleation were performed successfully by
      laparoscopy. The pathology report revealed mucinous cystadenoma. The patient had
      a smooth pregnancy course and delivered a healthy baby at 39 weeks of gestation.
      CONCLUSION: Laparoscopic surgery is a safe procedure in the management of
      pregnant women with suspicious adnexal cystic lesions.

PMID- 23548232
TI  - Prenatal diagnosis and molecular cytogenetic characterization of a de novo
      interstitial duplication of 11q (11q22.3->q23.3) associated with abnormal
      maternal serum biochemistry.
AB  - OBJECTIVE: To present prenatal diagnosis and molecular cytogenetic
      characterization of a de novo interstitial duplication of 11q (11q22.3->q23.3) in
      a pregnancy associated with abnormal maternal serum biochemistry. CASE REPORT: A
      33-year-old woman underwent amniocentesis in the second trimester because of
      abnormal maternal serum biochemistry. Her husband was 33 years old. At 17 weeks
      of gestation, the levels of alpha-fetoprotein (AFP), unconjugated estriol (uE3),
      total beta-human chorionic gonadotropin (beta-hCG), and inhibin A were 0.65
      multiples of median (MoM), 0.61 MoM, 0.32 MoM, and 0.55 MoM, respectively,
      consistent with a positive trisomy 18 risk of 1/128. Results of amniocentesis
      revealed a small de novo interstitial duplication of 11q encompassing 11q23. An
      array comparative genomic hybridization analysis detected a 9.04-Mb duplication
      at chromosome 11q22.3-q23.3. A polymorphic DNA marker analysis was carried out,
      which determined a paternal origin of the duplication. Results of fluorescence in
      situ hybridization analysis showed a direct duplication of interstitial 11q. The
      karyotype was 46,XX,dup(11)(q22.3q23.3). Level II ultrasound was unremarkable.
      The parents opted to continue the pregnancy. A 2792-g female baby was delivered
      at 38 weeks of gestation. When examined at 10 months of age, the neonate was
      small for age and was abnormal in psychomotor development with apparent facial
      dysmorphisms, and small hands and feet. CONCLUSION: Low levels of AFP, uE3, beta
      hCG, and inhibin A in the second trimester maternal serum biochemistry may be a
      distinctive prenatal feature in pregnancy with fetal chromosome 11q duplication.

PMID- 23548233
TI  - Prenatal diagnosis and molecular cytogenetic characterization of a de novo
      interstitial duplication of 14q (14q31.3->q32.12) associated with abnormal
      maternal serum biochemistry.
AB  - OBJECTIVE: To present prenatal diagnosis and molecular cytogenetic
      characterization of a de novo interstitial duplication of 14q (14q31.3->q32.12)
      in a pregnancy associated with abnormal maternal serum biochemistry. CASE REPORT:
      A 19-year-old woman underwent amniocentesis in the second trimester because of
      abnormal maternal serum biochemistry. Her husband was 33 years old. At 16 weeks
      of gestation, the levels of alpha-fetoprotein, unconjugated estriol, total beta
      human chorionic gonadotropin, and inhibin A were 0.8 multiples of median (MoM),
      0.84 MoM, 3.06 MoM, and 1.14 MoM, respectively, consistent with a positive
      trisomy 21 risk of 1/269. Results of an amniocentesis revealed a small de novo
      interstitial duplication of 14q encompassing 14q31-q32.1. An array comparative
      genomic hybridization analysis detected a 6.6-Mb duplication at chromosome
      14q31.3-q32.12. Results of a fluorescence in situ hybridization analysis showed a
      direct duplication of interstitial 14q. The karyotype was 46,XY,dup(14)
      (q31.3q32.12). Level II ultrasound was unremarkable. The parents decided to
      continue the pregnancy. A 3805-g healthy male baby was delivered at 39 weeks of
      gestation. When examined at 6 months of age, the neonate was normal in growth and
      psychomotor development with no apparent phenotypic abnormalities, although long
      term follow-ups are required. CONCLUSION: Abnormal maternal serum biochemistry in
      the second trimester may be a distinctive prenatal feature in pregnancy
      associated with fetal chromosome 14q duplication.

PMID- 23548234
TI  - An adenomyomatous polyp presenting as a large hypervascular tumor and its
      response to a gonadotropin-releasing hormone agonist.

PMID- 23548235
TI  - Prenatal diagnosis of pentalogy of Cantrell using three-dimensional ultrasound.

PMID- 23548236
TI  - Hemoperitoneum secondary to rupture of a superficial uterine artery overlying a
      subserous myoma with no predisposing factors in a young woman.

PMID- 23548237
TI  - Chronic pelvic pain secondary to leiomyoma of the round ligament.

PMID- 23548238
TI  - Ultrasound appearance and alternative management of postvaginal delivery placenta
      accreta.

PMID- 23548239
TI  - Uterus-sparing myomectomy for uterine pyomyoma following cesarean section.

PMID- 23548240
TI  - Bilateral retinal detachment with subsequent blindness in a pregnant woman with
      severe pre-eclampsia.

PMID- 23548241
TI  - Discrepancy in the trisomy mosaicism level between cultured amniocytes and
      uncultured amniocytes in prenatally detected mosaic trisomy 20.

PMID- 23548242
TI  - Prenatal diagnosis and molecular cytogenetic characterization of a proximal
      deletion of 22q (22q11.2->q11.21).

PMID- 23548243
TI  - Prenatal diagnosis of a missense mutation of c.2279G>A, Gly760Glu in exon 37 of
      COL1A2 in a fetus with familial osteogenesis imperfecta type IV and favorable
      outcome.

PMID- 23548244
TI  - Placental mesenchymal dysplasia associated with antepartum hemorrhage,
      subchorionic hematoma, and intrauterine growth restriction.

PMID- 23548245
TI  - Factors influencing the occurrence of pelvic cellulitis in women undergoing
      laparoscopic-assisted vaginal hysterectomy.

PMID- 23548246
TI  - Serum levels of visfatin and possible interaction with iron parameters in
      gestational diabetes mellitus.
AB  - BACKGROUND/AIMS: Visfatin is a novel adipokine with insulinomimetic properties
      that increases in diabetes. However, for gestational diabetes mellitus (GDM)
      there are conflicting reports. Recent studies have reported a positive
      association of serum ferritin concentrations with insulin resistance. Thus, we
      assessed serum levels of visfatin in pregnant women with varying degrees of
      glucose tolerance and investigated the possible interaction of visfatin with
      parameters of iron metabolism. METHODS: Visfatin levels were measured at 24-28
      weeks of gestation in 88 women who were divided into three groups according to
      their response to a 50-gram glucose challenge test and a 100-gram oral glucose
      tolerance test: control group (n = 28), impaired glucose tolerance (IGT) group (n
      = 30) and GDM group (n = 30). RESULTS: Visfatin levels were significantly higher
      in the GDM and IGT group than in control (p < 0.001 for GDM vs. control, and p =
      0.004 for IGT vs. control). Serum visfatin was significantly associated with
      serum ferritin, insulin, age, gravidity, and body mass index. In a linear
      regression model, the covariates explained only 17% of variability of serum
      visfatin concentration. Body mass index (p < 0.001) contributed independently to
      visfatin variance. CONCLUSION: Serum visfatin concentration is significantly
      higher in GDM and is correlated with ferritin levels.

PMID- 23548247
TI  - A PPARgamma ligand present in Actinidia fruit (Actinidia chrysantha) is
      identified as dilinolenoyl galactosyl glycerol.
AB  - Activity-guided fractionation of Actinidia fruit species, including Kiwifruit,
      has identified DLGG (dilinolenoyl galactosyl glycerol) as a potent PPARgamma
      (peroxisome-proliferator-activated receptor gamma) ligand. DLGG is a type of MGDG
      (monogalactosyl diacylglycerol) and is present in all chloroplasts, and therefore
      all green fruits and vegetables. PPARgamma is a ligand-activated transcription
      factor that regulates glucose metabolism and inflammation. An ethyl acetate
      extract of Actinidia chrysantha was fractionated by HPLC and the PPARgamma
      binding activity was detected by FP (fluorescence polarization). Linoleic and
      alpha-linolenic acids in A. chrysantha were readily detected as PPARgamma
      ligands. Slow-binding PPARgamma ligands were detected in several hydrophobic
      fractions. High-resolution MS identified DLGG as one of these ligands and
      confirmed that its binding is non-covalent. DLGG is a slow-binding PPARgamma
      ligand with an IC50 of 1.64 MUM, +/-0.093 achieved after 45 min equilibration.
      DLGG is the first example of a form of DAG (diacylglycerol) that is a PPARgamma
      ligand. In addition, DLGG is the first reported glycolipid ligand for PPARgamma
      and also the first non-covalent, slow-binding PPARgamma ligand. 

PMID- 23548248
TI  - Reduced glucocorticoid receptor protein expression in children with critical
      illness.
AB  - BACKGROUND/AIMS: The diagnostic criteria for critical illness-related corticoid
      insufficiency (CIRCI) are not well established, particularly for children. In
      addition to alterations in adrenal function, cellular resistance to
      glucocorticoid action could contribute to CIRCI due to alterations in the
      functioning of the intracellular receptor protein for corticosteroids, the
      glucocorticoid receptor (GR). METHODS: We have therefore undertaken a pilot,
      prospective study to assess whether cellular GR activity can be measured in
      peripheral blood mononuclear cells (PBMCs) from critically ill children. RESULTS:
      Total and cytoplasmic, but not nuclear GR levels were significantly lower in
      PBMCs from critically ill children (i.e. sepsis/septic shock and traumatic brain
      injury) compared to healthy controls . While total cortisol concentrations did
      not differ between test groups, salivary and serum-free cortisol concentrations
      were significantly greater in both groups of children with critical illness.
      Cortisol-binding globulin levels were significantly lower in patients with
      sepsis/septic shock. CONCLUSIONS: The lower total and cytoplasmic receptor levels
      in critically ill children suggest that the GR-mediated response to exogenous
      glucocorticoid therapy may be limited. However, the nuclear transport of GR in
      critically ill patients suggests that residual receptors in these patients retain
      functionality and may be accessible to therapeutic treatments that maximize their
      activity.

PMID- 23548249
TI  - C-X-C motif receptor 2, endostatin and proteinase-activated receptor 1
      polymorphisms as prognostic factors in NSCLC.
AB  - The progress of non-small cell lung cancer (NSCLC) is dependent on sufficient
      angiogenesis. Thrombin induced activation of proteinase-activated receptor 1 (PAR
      1) on platelets leads to platelet secretion and aggregation. This influences cell
      survival, apoptosis and angiogenesis by the release of VEGF and Endostatin (ES),
      a potent angiogenesis inhibitor. Interleukin-8 (IL-8) induces tumor angiogenesis
      independent of the VEGF pathway through the chemokine C-X-C motif receptor 2
      (CXCR-2). Our purpose was to evaluate germline polymorphisms of these potential
      therapy targets as prognostic markers for disease free survival (DFS) and overall
      survival (OS) in surgically treated NSCLC patients. In total 209 Caucasian
      patients, treated between 1996 and 2011, were included in this study. Genomic DNA
      was extracted from peripheral blood leucocytes. Genotyping of CXCR-2 +1208 C > T
      and +785 C > T, PAR-1 -506 Ins/del and -14 Ivs A > T and ES +4349 G > A was
      performed by TaqMan((r)) genotyping assays or by polymerase chain reaction (PCR)
      followed by capillary electrophoresis. Chi-square test, Kaplan-Meier estimator
      and cox regression hazard model were used to assess the prognostic value of
      selected polymorphisms. The PAR-1 -14 Ivs A/A genotype was associated with
      advanced tumor stages (p = 0.024) and, in univariate analysis, with shorter
      median OS in squamous cell lung carcinoma (SqCC, p = 0.035). The CXCR-2 + 1208T/T
      genotype was associated with aggressive tumor biology (p = 0.038), and shorter
      DFS and OS (p = 0.018, p = 0.021) in NSCLC and especially in SqCC a negative
      predictor for DFS and OS (p = 0.045, p = 0.041). Genotyping of the CXCR-2 +1208 C
      >T polymorphism could be a useful tool to identify high-risk SqCC subgroups.

PMID- 23548250
TI  - Guided internet-delivered acceptance and commitment therapy for chronic pain
      patients: a randomized controlled trial.
AB  - Acceptance and commitment therapy (ACT) interventions for persons with chronic
      pain have recently received empirical support. ACT focuses on reducing the
      disabling influences of pain through targeting ineffective control strategies and
      teaches people to stay in contact with unpleasant emotions, sensations, and
      thoughts. The aim of the present study was to investigate the effect of a guided
      internet-delivered ACT intervention for persons with chronic pain. A total of 76
      patients with chronic pain were included in the study and randomized to either
      treatment for 7 weeks or to a control group that participated in a moderated
      online discussion forum. Intent-to-treat analyses showed significant increases
      regarding activity engagement and pain willingness. Measurements were provided
      with the primary outcome variable Chronic Pain Acceptance Questionnaire which was
      in favour of the treatment group. Reductions were found on other measures of pain
      related distress, anxiety and depressive symptoms. A six month follow-up showed
      maintenance of improvements. We conclude that an acceptance based internet
      delivered treatment can be effective for persons with chronic pain.

PMID- 23548251
TI  - Efficacy of misoprostol administration 24 hours after mifepristone for
      termination of early pregnancy.
AB  - INTRODUCTION: Mifepristone and misoprostol are the two drugs which are given at
      36-48 h interval for medical abortion. This study was designed to study the
      efficacy of early administration of misoprostol (24 h after mifepristone) for
      medical termination of pregnancy less than 9 weeks and to compare this with
      standard protocol of mifepristone misoprostol combination at 48 h interval.
      MATERIALS AND METHODS: Subjects for this single center prospective randomized
      case-control study were enrolled from the family planning outdoor patient
      department at our hospital with gestational age of less than 9 weeks. All
      subjects initially received 200 mg of oral mifepristone and then were randomly
      assigned to receive per vaginal 400 MUg misoprostol at 24 h (study group) and 48
      h (control group). They were then followed up after 14 days with transvaginal
      sonography to confirm completion of expulsion. Treatment was considered failed if
      surgical evacuation was needed for any indication. Primary outcome measure was
      success rate of the two treatment regimens. RESULTS: Totally, 200 subjects were
      randomly allocated to each treatment arm (100 each). Complete expulsion was seen
      in 94% (94/100) in study group and 95% (95/100) in control group according to
      intention to treat analysis (P value ns). According to per protocol analysis
      success rate in study group was 93.6% and 94.3% in control group (P value ns).
      High failure rate after 7 weeks period of gestation in both the study and control
      group was found (26.3% and 30.0%; P value ns). Adverse effects were mostly
      similar in both the groups. CONCLUSION: Efficacy of mifepristone misoprostol
      combination at 24 h interval was similar to that at 48 h interval for medical
      abortion of pregnancy less than 9 weeks without compromising the safety .

PMID- 23548252
TI  - Validity of simple, novel measures of generalized and central obesity among young
      Asian Indian women.
AB  - OBJECTIVE: The study examined the validity of simple and novel measures of
      generalized obesity- [body mass index (BMI, kg/m2), fat mass index (FMI, kg/m2),
      and body fat percent (BF%)] and central obesity--[waist circumference (WC, cm),
      waist-hip ratio (WHR), and waist-to-height ratio (WC/ht ratio)] against BF% and
      BMI as criteria. It also aimed to predict fat-free mass index (FFMI, kg/m 2 ),
      FMI, and BF% ranges for various BMI categories. DESIGN: Cross-sectional study.
      MATERIALS AND METHODS: Weight, BF%, fat mass (FM), and fat-free mass (FFM) were
      measured using leg-to-leg bioelectrical impedance in 183 women. Height, hip, and
      waist circumferences were taken using standard methods. The indices [FMI, FFMI,
      WHR, W/ht ratio] were computed. RESULTS: The study revealed that FMI, BMI, WC,
      and WC/ht ratio were highly correlated with BF% (r = 0.978; r = 0.939; r = 0.894;
      r = 0.890, respectively, P < 0.01), whereas WHR had the least correlation (r =
      0.497, P < 0.01). The FMI showed a higher positive predictive value (PPV) in
      diagnosing generalized obesity compared to BMI with BF% as criterion and higher
      PPV than BF% with BMI as criterion. Considering only the indices of central
      obesity, WC was the most predictive in identifying women with high BF% (>= 30%
      and >= 35%), whereas WC/ht ratio proved to be a better index in identifying women
      with BMI greater than 23 and 25 kg/m2. The normal BMI for Asians (18.5-23 kg/m 2
      ), the at-risk group (23- 25 kg/m2), and the obese class I (25-30 kg/m2)
      corresponded to FFMI values of 14.1-15.1 kg/m 2, 15.1-15.5 kg/m 2, 15.5-16.1 kg/m
      2, respectively, and to FMI values of 4.4-7.9 kg/m 2, 7.9-9.5 kg/m 2, 9.5-13.9
      kg/m 2, respectively. The BMI cutoff of 18.5, 23, 25, 27.5, and 30 kg/m 2
      corresponded to BF% of 23.6, 34.3, 38.3, 42.6, and 46.3%, respectively.
      CONCLUSION: FMI was a better predictor of generalized obesity compared to BMI and
      BF%. Considering abdominal obesity as an independent risk factor for insulin
      resistance, both WC and WC/ht ratio were able to predict central obesity better
      than WHR. Finally, the study presents ranges for FFMI and FMI for various BMI
      categories.

PMID- 23548253
TI  - Socio-demographic profile of pregnant women using mishri.
AB  - BACKGROUND: "Mishri" is one among the various smokeless tobacco products used in
      the central and southern part of India. The use of newer tobacco products is
      increasing not only among men, but also among children, teenagers, and women of
      the reproductive age-group. OBJECTIVES: To study socio-demographic profile of
      mishri users among pregnant women admitted for delivery into Krishna Hospital,
      Karad - Satara, Maharashtra. MATERIALS AND METHODS: All the consecutive pregnant
      women admitted for delivery in Krishna Hospital, Karad over a period of 6 months
      were enrolled and a detailed history of use of tobacco was obtained from them. A
      representative sample of mishri used by them for each application was collected
      and weighed on an electronic weighing machine. The socio-demographic information
      was collected among all mishri users and age-, parity-matched controls of non
      mishri users during pregnancy. RESULTS: A total of 258, i.e., (12%) of the women
      delivering in Krishna Hospital were using mishri. The mean duration of mishri use
      was 2 years with a standard deviation (SD) of 1.09 years, frequency of daily
      application being 1.4 times with an SD of 0.55, dwell time in mouth being 10 min
      with an SD of 2.9 min, and the quantity of each application being 236 mg with an
      SD of 66.2 mg. 29% of the teenagers and 68% of the primiparas were found to be
      using mishri, and a majority of them were housewives, having minimum education
      and belonging to the middle and lower socio-economic class. It was also found
      that the family members played a role in influencing the habit of mishri use.
      INTERPRETATION AND CONCLUSION: A small but significant number of women who
      deliver in the hospital used mishri during pregnancy and were in need of de
      addiction counseling.

PMID- 23548254
TI  - Management of early onset severe preeclampsia in a tertiary hospital in India:
      does expectant management alter perinatal outcome?
AB  - OBJECTIVE: The aims of the study were to find out the maternal and perinatal
      outcome of early onset severe preeclampsia (PE) in a tertiary care center in a
      developing country like India and to determine whether expectant management in
      such a setup improves the perinatal outcome. MATERIALS AND METHODS: It was a
      retrospective study. All women with early PE were admitted stabilized and
      evaluated. Expectant management was given whenever there was no indication for
      eminent delivery. The perinatal outcome of the expectant group was compared with
      that of the aggressive group, and appropriate statistical analysis was carried
      out. RESULTS: A total of 106 women were admitted with severe PE, 61 were treated
      aggressively, and 45 were stable enough to receive expectant management. The
      total days gained on expectant management was 7 days. Perinatal mortality was
      31.13%. Perinatal outcome of the expectant and aggressive management groups did
      not differ (P = 0.141); there was no increase in maternal complications on
      expectant management. There were 2 cases of maternal mortality in the
      aggressively managed group. CONCLUSION: Perinatal mortality in severe PE is high.
      There was no increase in maternal morbidity on expectant management; however,
      there was no difference in perinatal mortality on expectant management.

PMID- 23548255
TI  - Hydatid cyst of liver: a case with an unusual clinical presentation.
AB  - Hydatid cyst caused by the parasite Echinococcus most commonly involve liver and
      usually presented with right hypochondrial pain which may be associated with
      jaundice, urticarial skin rashes, pruritus etc., We report here a case of 32
      years old young lady who clinically presented with acute exacerbation of
      bronchial asthma of recent onset. Her chest x-ray was unremarkable except
      slightly pushed up diaphragm on right side. Ultrasonography of abdomen revealed a
      cyst in the right lobe of liver, suggestive of hydatid cyst. Following
      confirmation of diagnosis by computed tomography (CT)-guided Fine Needle
      Aspiration Cytology (FNAC) surgical resection of the cystic lesion was done. On
      subsequent follow up for one year she was found to be cured of bronchial asthma.
      This case of hepatic hydatid cyst is reported here for its unique clinical
      presentation exclusively with bronchial asthma which completely subsided with
      resection of the cyst.

PMID- 23548256
TI  - Evaluation of resistance of commonly used antibiotics on clinical case of
      Staphylococcus capitis from Assir region, Saudi Arabia.
AB  - Staphylococcus capitis is a coagulase-negative species (CoNS) of Staphylococcus.
      It causes antimicrobial resistance for nosocomial infections as well as for
      community-acquired infections. This case report involves a 51-year-old, married
      Saudi patient. He got admitted to the male medical ward of Aseer Central
      Hospital, with severe chest infection. Clinical examination, X-ray, and
      laboratory investigations were performed which involved bactech, culture media,
      antibiotic sensitivity test using disk diffusion [minimum inhibitory
      concentration (MIC)] and molecular [polymerase chain reaction (PCR)] for
      detection of CoNS of Staphylococcus species and detection of the mecA gene.
      Laboratory data were recorded in special formats and analyzed by statistical
      computer program (SPSS). Results showed the resistance of isolated S. capitis to
      many commonly used antibiotics.

PMID- 23548257
TI  - Intramuscular, extraskeletal mesenchymal chondrosarcoma.
AB  - Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare and a malignant
      chondrogenic neoplasm. As a particularity of this neoplasm, about one-third of
      the cases develop outside the bone, with intramuscular site being a very rare
      location for development of EMC. The diagnosis of mesenchymal chondrosarcoma can
      be very challenging, especially in cases without conspicuous cartilaginous
      differentiation. In such cases its distinction from other small cell mesenchymal
      neoplasms cannot be safely established. This, however, is of major clinical
      interest as it implicates different treatment protocols as well as a different
      prognosis. We hereby present a case of EMC at a unusual location in a 23-year-old
      female with the purpose to highlight its morphologic features and to discuss its
      differential diagnosis.

PMID- 23548258
TI  - Childhood blindness: is my world getting smaller?

PMID- 23548259
TI  - Comparative efficacy of sunitinib versus sorafenib as first-line treatment for
      patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: This study investigated the efficacy and toxicity of sorafenib and
      sunitinib as primary treatment for patients with metastatic renal cell carcinoma
      (mRCC). METHODS: We identified 49 and 220 patients treated with sorafenib and
      sunitinib, respectively, as first-line therapy in the Asan Medical Centre from
      April 2005 to March 2011. RESULTS: Disease control rates of 71 and 74% were
      achieved with sorafenib and sunitinib, respectively (p = 0.687). After a median
      follow-up of 27.6 months, progression-free survival (PFS) and overall survival
      (OS) were not significantly different between the sorafenib and the sunitinib
      group (PFS 8.6 vs. 9.9 months, respectively, p = 0.948, and OS 25.7 vs. 22.6
      months, p = 0.774). Patients treated with sorafenib required dose reduction due
      to toxicities less frequently than those treated with sunitinib (37 vs. 54%, p =
      0.034). Haematological toxicity of grade 3 or 4 was more common in the sunitinib
      group than in the sorafenib group (45 vs. 4%, p < 0.001). Multivariate analysis
      showed old age, Heng's risk group, and bone and liver metastases, but not the
      type of vascular endothelial growth factor tyrosine kinase inhibitor, were
      independent prognostic factors affecting OS. CONCLUSION: The results of this
      study indicate that sorafenib has comparable efficacy to sunitinib in the
      treatment of mRCC patients and fewer and less severe toxicities, but the number
      of patients included in the study was small.

PMID- 23548260
TI  - Solifenacin succinate versus percutaneous tibial nerve stimulation in women with
      overactive bladder syndrome: results of a randomized controlled crossover study.
AB  - AIMS: This study compared the effectiveness of solifenacin succinate (SS) versus
      percutaneous tibial nerve stimulation (PTNS) in women with overactive bladder
      syndrome (OABS). METHODS: A randomized controlled crossover study of 40 women
      with OABS was performed. Patients were randomized into two groups. In group A,
      patients received SS and then PTNS. In group B, patients underwent PTNS and then
      SS. Voiding diaries, quality of life surveys and patient perception of intensity
      of urgency questionnaire were performed before and after each treatment. The
      global impression of improvement questionnaire was performed at the end of the
      study. RESULTS: A reduction in the number of daily micturitions, episodes of
      nocturia and urge incontinence were found with both SS and PTNS in all groups,
      but PTNS showed a greater effectiveness than SS. There was an increase in voided
      volume in all groups with both SS and PTNS, but patients treated with PTNS had a
      greater increase. PTNS showed greater effectiveness in patient perception of
      urgency and quality of life. CONCLUSION: This study demonstrates the
      effectiveness of SS and PTNS In women with overactive bladder symptoms. However,
      greater improvements were found with PTNS.

PMID- 23548261
TI  - Human exposure assessment of indoor dust: Webster and Stapleton respond.

PMID- 23548262
TI  - Does mindfulness matter? Everyday mindfulness, mindful eating and self-reported
      serving size of energy dense foods among a sample of South Australian adults.
AB  - Serving size is a modifiable determinant of energy consumption, and an important
      factor to address in the prevention and treatment of obesity. The present study
      tested an hypothesised negative association between individuals' everyday
      mindfulness and self-reported serving size of energy dense foods. The mediating
      role of mindful eating was also explored. A community sample of 171 South
      Australian adults completed self-report measures of everyday mindfulness and
      mindful eating. The dependent measure was participants' self-reported average
      serving size of energy dense foods consumed in the preceding week. Participants
      who reported higher levels of everyday mindfulness were more mindful eaters
      (r=0.41, p<0.05) and reported smaller serving size estimates of energy dense
      foods (r=-.25, p<0.05). Mindful eating fully mediated the negative association
      between everyday mindfulness and serving size. The domains of mindful eating most
      relevant to serving size included emotional and disinhibited eating. Results
      suggest that mindful eating may have a greater influence on serving size than
      daily mindfulness.

PMID- 23548263
TI  - Web 2.0-based crowdsourcing for high-quality gold standard development in
      clinical natural language processing.
AB  - BACKGROUND: A high-quality gold standard is vital for supervised, machine
      learning-based, clinical natural language processing (NLP) systems. In clinical
      NLP projects, expert annotators traditionally create the gold standard. However,
      traditional annotation is expensive and time-consuming. To reduce the cost of
      annotation, general NLP projects have turned to crowdsourcing based on Web 2.0
      technology, which involves submitting smaller subtasks to a coordinated
      marketplace of workers on the Internet. Many studies have been conducted in the
      area of crowdsourcing, but only a few have focused on tasks in the general NLP
      field and only a handful in the biomedical domain, usually based upon very small
      pilot sample sizes. In addition, the quality of the crowdsourced biomedical NLP
      corpora were never exceptional when compared to traditionally-developed gold
      standards. The previously reported results on medical named entity annotation
      task showed a 0.68 F-measure based agreement between crowdsourced and
      traditionally-developed corpora. OBJECTIVE: Building upon previous work from the
      general crowdsourcing research, this study investigated the usability of
      crowdsourcing in the clinical NLP domain with special emphasis on achieving high
      agreement between crowdsourced and traditionally-developed corpora. METHODS: To
      build the gold standard for evaluating the crowdsourcing workers' performance,
      1042 clinical trial announcements (CTAs) from the ClinicalTrials.gov website were
      randomly selected and double annotated for medication names, medication types,
      and linked attributes. For the experiments, we used CrowdFlower, an Amazon
      Mechanical Turk-based crowdsourcing platform. We calculated sensitivity,
      precision, and F-measure to evaluate the quality of the crowd's work and tested
      the statistical significance (P<.001, chi-square test) to detect differences
      between the crowdsourced and traditionally-developed annotations. RESULTS: The
      agreement between the crowd's annotations and the traditionally-generated corpora
      was high for: (1) annotations (0.87, F-measure for medication names; 0.73,
      medication types), (2) correction of previous annotations (0.90, medication
      names; 0.76, medication types), and excellent for (3) linking medications with
      their attributes (0.96). Simple voting provided the best judgment aggregation
      approach. There was no statistically significant difference between the crowd and
      traditionally-generated corpora. Our results showed a 27.9% improvement over
      previously reported results on medication named entity annotation task.
      CONCLUSIONS: This study offers three contributions. First, we proved that
      crowdsourcing is a feasible, inexpensive, fast, and practical approach to collect
      high-quality annotations for clinical text (when protected health information was
      excluded). We believe that well-designed user interfaces and rigorous quality
      control strategy for entity annotation and linking were critical to the success
      of this work. Second, as a further contribution to the Internet-based
      crowdsourcing field, we will publicly release the JavaScript and CrowdFlower
      Markup Language infrastructure code that is necessary to utilize CrowdFlower's
      quality control and crowdsourcing interfaces for named entity annotations.
      Finally, to spur future research, we will release the CTA annotations that were
      generated by traditional and crowdsourced approaches.

PMID- 23548264
TI  - A novel inhibitor of c-Met and VEGF receptor tyrosine kinases with a broad
      spectrum of in vivo antitumor activities.
AB  - The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor
      (HGF), are dysregulated in a wide variety of human cancers and are linked with
      tumorigenesis and metastatic progression. VEGF also plays a key role in tumor
      angiogenesis and progression by stimulating the proangiogenic signaling of
      endothelial cells via activation of VEGF receptor tyrosine kinases (VEGFR).
      Therefore, inhibiting both HGF/c-Met and VEGF/VEGFR signaling may provide a novel
      therapeutic approach for treating patients with a broad spectrum of tumors.
      Toward this goal, we generated and characterized T-1840383, a small-molecule
      kinase inhibitor that targets both c-Met and VEGFRs. T-1840383 inhibited HGF
      induced c-Met phosphorylation and VEGF-induced VEGFR-2 phosphorylation in cancer
      epithelial cells and vascular endothelial cells, respectively. It also inhibited
      constitutively activated c-Met phosphorylation in c-met-amplified cancer cells,
      leading to suppression of cell proliferation. In addition, T-1840383 potently
      blocked VEGF-dependent proliferation and capillary tube formation of endothelial
      cells. Following oral administration, T-1840383 showed potent antitumor efficacy
      in a wide variety of human tumor xenograft mouse models, along with reduction of
      c-Met phosphorylation levels and microvessel density within tumor xenografts.
      These results suggest that the efficacy of T-1840383 is produced by direct
      effects on tumor cell growth and by an antiangiogenic mechanism. Furthermore, T
      1840383 showed profound antitumor activity in a gastric tumor peritoneal
      dissemination model. Collectively, our findings indicate the therapeutic
      potential of targeting both c-Met and VEGFRs simultaneously with a single small
      molecule inhibitor for the treatment of human cancers.

PMID- 23548265
TI  - Synergistic anticancer activity of arsenic trioxide with erlotinib is based on
      inhibition of EGFR-mediated DNA double-strand break repair.
AB  - Arsenic trioxide (ATO), one of the oldest remedies used in traditional medicine,
      was recently rediscovered as an anticancer drug and approved for treatment of
      relapsed acute promyelocytic leukemia. However, its activity against
      nonhematologic cancers is rather limited so far. Here, we show that inhibition of
      ATO-mediated EGF receptor (EGFR) activation can be used to potently sensitize
      diverse solid cancer types against ATO. Thus, combination of ATO and the EGFR
      inhibitor erlotinib exerted synergistic activity against multiple cancer cell
      lines. Subsequent analyses revealed that this effect was based on the blockade of
      ATO-induced EGFR phosphorylation leading to more pronounced G2-M arrest as well
      as enhanced and more rapid induction of apoptosis. Comparable ATO-sensitizing
      effects were also found with PI3K/AKT and mitogen-activated protein/extracellular
      signal-regulated kinase (MEK) inhibitors, suggesting an essential role of the
      EGFR-mediated downstream signaling pathway in cancer cell protection against ATO.
      H2AX staining and comet assay revealed that erlotinib significantly increases ATO
      induced DNA double-strand breaks (DSB) well in accordance with a role of the EGFR
      signaling axis in DNA damage repair. Indeed, EGFR inhibition led to
      downregulation of several DNA DSB repair proteins such as Rad51 and Rad50 as well
      as reduced phosphorylation of BRCA1. Finally, the combination treatment of ATO
      and erlotinib was also distinctly superior to both monotreatments against the
      notoriously therapy-resistant human A549 lung cancer and the orthotopic p31
      mesothelioma xenograft model in vivo. In conclusion, this study suggests that
      combination of ATO and EGFR inhibitors is a promising therapeutic strategy
      against various solid tumors harboring wild-type EGFR.

PMID- 23548266
TI  - Assessment of renal function by means of cystatin C following standard and
      fenestrated endovascular aneurysm repair.
AB  - BACKGROUND: Cystatin C (Cyst C) is more sensitive marker for early renal injury.
      However, serum creatinine (sCr) and estimated glomerular filtration rate (eGFR)
      are still used as the standard renal markers after endovascular aortic aneurysm
      repair (EVAR). The goal of this study was to compare the efficacy of Cyst C, sCr,
      and eGFR as markers of renal function after EVAR. PATIENTS AND METHODS: This
      study examined 29 patients (27 men) with a mean age of 76.9 years (range, 55-89
      years) undergoing standard (n = 19) and fenestrated (n = 10) EVAR for abdominal
      aortic aneurysm (AAA) of mean diameter 6.9 cm (range, 5.5-10 cm). Cyst C and sCr
      were measured and eGFR calculated before and 1 day and 1, 6, and 12 months after
      EVAR. RESULTS: At 24 hours after procedure, a significant increase in Cyst C (P <
      0.005) and sCr (P = 0.028) and significant decrease in eGFR (P = 0.04) were seen.
      Cyst C continued to increase and was significantly higher at 1 (P < 0.002), 6 (P
      < 0.005), and 12 (P < 0.005) months compared with baseline. By contrast, sCr and
      eGFR did not show any significant change at 1, 6, and 12 months from the baseline
      level. Cyst C increased significantly postoperatively regardless of the baseline
      renal function. None of the patients required renal replacement therapy.
      CONCLUSIONS: EVAR is associated with a significant increase in Cyst C starting 24
      hours after the procedure and is maintained for 12 months. sCr and eGFR only show
      significant change at 24 hours and therefore may underestimate long-term renal
      damage after EVAR.

PMID- 23548267
TI  - Concurrent basilar artery double fenestration with aneurysm and vertebral artery
      dissection: case report and literature review of rare cerebrovascular
      abnormalities.
AB  - Many disorders can cause aneurysm and/or dissection of the cerebral arteries,
      including fibromuscular dysplasia (FMD), connective tissue disorders, cerebral
      vasculitis, infection, and vascular malformations. Arterial fenestration is a
      rare congenital finding that can also cause aneurysms, and can rarely dissect and
      bleed. Treatment of aneurysm and dissection with subarachnoid hemorrhage can be
      very complicated, and requires case-by-case analysis of the risks and benefits of
      antithrombotic therapy. To the authors' knowledge, no case of double fenestration
      of the basilar artery has been reported. This report presents a case of
      concurring vertebral artery dissection and double fenestration of the basilar
      artery with aneurysm. The fenestration and FMD are considered possible main
      contributing causes of this presentation. A literature review of cerebrovascular
      fenestration and FMD is provided and the relationship between the 2 is
      considered. Lastly, the use of antithrombotic therapy in the setting of
      subarachnoid hemorrhage, dissection, and stent placement is discussed.

PMID- 23548268
TI  - Local ischaemia does not influence anastomotic healing: an experimental study.
AB  - The role of local ischaemia in the pathogenesis of colorectal anastomotic leakage
      (AL) is not known. This study investigates the role of local ischaemia caused by
      sutures in an experimental colonic anastomosis model. 36 mice were assigned to
      three types of anastomosis, all using running sutures; in the first group 5
      stitches were used, in the second group 12 stitches were used, and in the third
      group at least 30 stitches were used. After 7 days the mice were re-operated,
      signs of AL were scored, and coronal sections of the anastomosis were
      histologically analyzed. The distribution of weight was not significantly
      different between the three groups. Mortality was 44% and not significantly
      different between the groups (group 1: 5/12, group 2: 4/12, and group 3: 7/12, p
      = 0.72). Faecal and purulent AL were observed in 6 animals in group 1, 2 in group
      2, and 3 in group 3 (group 1: 50%, group 2: 17%, and group 3: 25%, p = 0.19). The
      distance between the two colonic edges (group 1: 0.51 MUm, group 2: 1.34 MUm, and
      group 3: 0.53 MUm, p = 0.18), the diameter of the lumen at the site of the
      anastomosis (group 1: 2.92 MUm, group 2: 4.06 MUm, and group 3: 3.2 MUm, p =
      0.9), and the largest diameter of the lumen proximally to the anastomosis (group
      1: 2.05 MUm, group 2: 3.1 MUm, and group 3: 2.6 MUm, p = 0.25) were not different
      between the groups. Histological parameters of wound healing were not
      significantly different for the three groups. In this study no macroscopic and
      microscopic differences were observed between colon anastomosis with 5 stitches
      versus 12 and >30 stitches. This might indicate that local ischaemia does not
      negatively influence colonic wound healing.

PMID- 23548270
TI  - miR145 targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6
      mediated paracrine effects in head and neck cancer.
AB  - ALDH1(+)CD44(+) cells are putative tumor-initiating cells (TIC) in head and neck
      squamous cell carcinomas (HNC). miR-145 regulates tumorigenicity in various
      cancers but the breadth of its mechanistic contributions and potential
      therapeutic applications are not completely known. Here, we report that
      ALDH1(+)CD44(+)-HNC cells express reduced levels of miR145. SPONGE-mediated
      inhibition of miR-145 (Spg-miR145) was sufficient to drive tumor-initiating
      characteristics in non-TICs/ALDH1(-)CD44-negative HNC cells. Mechanistic analyses
      identified SOX9 and ADAM17 as two novel miR145 targets relevant to this process.
      miR-145 expression repressed TICs in HNC in a manner associated with SOX9
      interaction with the ADAM17 promoter, thereby activating ADAM17 expression.
      Notably, the SOX9/ADAM17 axis dominated the TIC-inducing activity of miR-145.
      Either miR-145 suppression or ADAM17 overexpression in non-TICs/ALDH1(-)CD44(-)
      HNC cells increased expression and secretion of interleukin (IL)-6 and soluble-IL
      6 receptor (sIL-6R). Conversely, conditioned medium from Spg-miR145-transfected
      non-TICs/ALDH1(-)CD44(-)-HNC cells was sufficient to confer tumor-initiating
      properties in non-TICs/ALDH1(-)CD44(-)-HNC and this effect could be abrogated by
      an IL-6-neutralizing antibody. We found that curcumin administration increased
      miR-145 promoter activity, thereby decreasing SOX9/ADAM17 expression and
      eliminating TICs in HNC cell populations. Delivery of lentivral-miR145 or orally
      administered curcumin blocked tumor progression in HNC-TICs in murine
      xenotransplant assays. Finally, immunohistochemical analyses of patient specimens
      confirmed that an miR-145(low)/SOX9(high)/ADAM17(high) phenotype correlated with
      poor survival. Collectively, our results show how miR-145 targets the SOX9/ADAM17
      axis to regulate TIC properties in HNC, and how altering this pathway may partly
      explain the anticancer effects of curcumin. By inhibiting IL-6 and sIL-6R as
      downstream effector cytokines in this pathway, miR-145 seems to suppress a
      paracrine signaling pathway in the tumor microenvironment that is vital to
      maintain TICs in HNC.

PMID- 23548269
TI  - ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy
      independent of BRCA status.
AB  - Replication stress and DNA damage activate the ATR-Chk1 checkpoint signaling
      pathway that licenses repair and cell survival processes. In this study, we
      examined the respective roles of the ATR and Chk1 kinases in ovarian cancer cells
      using genetic and pharmacologic inhibitors in combination with cisplatin,
      topotecan, gemcitabine, and the PARP inhibitor veliparib (ABT-888), four agents
      with clinical activity in ovarian cancer. RNA interference (RNAi)-mediated
      depletion or inhibition of ATR sensitized ovarian cancer cells to all four
      agents. In contrast, while cisplatin, topotecan, and gemcitabine each activated
      Chk1, RNAi-mediated depletion or inhibition of this kinase in cells sensitized
      them only to gemcitabine. Unexpectedly, we found that neither the ATR kinase
      inhibitor VE-821 nor the Chk1 inhibitor MK-8776 blocked ATR-mediated Chk1
      phosphorylation or autophosphorylation, two commonly used readouts for inhibition
      of the ATR-Chk1 pathway. Instead, their ability to sensitize cells correlated
      with enhanced CDC25A levels. In addition, we also found that VE-821 could further
      sensitize BRCA1-depleted cells to cisplatin, topotecan, and veliparib beyond the
      potent sensitization already caused by their deficiency in homologous
      recombination. Taken together, our results established that ATR and Chk1
      inhibitors differentially sensitize ovarian cancer cells to commonly used
      chemotherapy agents and that Chk1 phosphorylation status may not offer a reliable
      marker for inhibition of the ATR-Chk1 pathway. A key implication of our work is
      the clinical rationale it provides to evaluate ATR inhibitors in combination with
      PARP inhibitors in BRCA1/2-deficient cells.

PMID- 23548271
TI  - The endogenous tryptophan metabolite and NAD+ precursor quinolinic acid confers
      resistance of gliomas to oxidative stress.
AB  - Quinolinic acid is a product of tryptophan degradation and may serve as a
      precursor for NAD(+), an important enzymatic cofactor for enzymes such as the DNA
      repair protein PARP. Pathologic accumulation of quinolinic acid has been found in
      neurodegenerative disorders including Alzheimer and Huntington disease, where it
      is thought to be toxic for neurons by activating the N-methyl-D-aspartate (NMDA)
      receptor and inducing excitotoxicity. Although many tumors including gliomas
      constitutively catabolize tryptophan, it is unclear whether quinolinic acid is
      produced in gliomas and whether it is involved in tumor progression. Here, we
      show that quinolinic acid accumulated in human gliomas and was associated with a
      malignant phenotype. Quinolinic acid was produced by microglial cells, as
      expression of the quinolinic acid-producing enzyme 3-hydroxyanthranilate
      oxygenase (3-HAO) was confined to microglia in glioma tissue. Human malignant
      glioma cells, but not nonneoplastic astrocytes, expressed quinolinic acid
      phosphoribosyltransferase (QPRT) to use quinolinic acid for NAD(+) synthesis and
      prevent apoptosis when de novo NAD(+) synthesis was blocked. Oxidative stress,
      temozolomide, and irradiation induced QPRT in glioma cells. QPRT expression
      increased with malignancy. In recurrent glioblastomas after radiochemotherapy,
      QPRT expression was associated with a poor prognosis in two independent datasets.
      Our data indicate that neoplastic transformation in astrocytes is associated with
      a QPRT-mediated switch in NAD(+) metabolism by exploiting microglia-derived
      quinolinic acid as an alternative source of replenishing intracellular NAD(+)
      pools. The elevated levels of QPRT expression increase resistance to oxidative
      stress induced by radiochemotherapy, conferring a poorer prognosis. These
      findings have implications for therapeutic approaches inducing intracellular
      NAD(+) depletion, such as alkylating agents or direct NAD(+) synthesis
      inhibitors, and identify QPRT as a potential therapeutic target in malignant
      gliomas.

PMID- 23548273
TI  - Acidophilic fungus, Teratosphaeria acidotherma AIU BGA-1, produces multiple forms
      of intracellular beta-galactosidase.
AB  - Teratosphaeria acidotherma AIU BGA-1 isolated from an acidic and high temperature
      hot spring produced four intracellular beta-D-galactosidases with different pH
      activity profiles, in which three forms were acidophilic and stable from
      extremely acidic to neutral pH region. The other one was alkalophilic and
      unstable in the acidic pH region.

PMID- 23548272
TI  - Improvement of recombinant endoglucanase produced in Pichia pastoris KM71 through
      the use of synthetic medium for inoculum and pH control of proteolysis.
AB  - The long lag time in basal salts medium (BSM) and an occurrence of proteolysis
      are major problems for recombinant protein production in Pichia pastoris KM71. In
      this study, optimal conditions were explored for fed-batch cultivation of
      recombinant fungal endoglucanase in P. pastoris KM71. It was found that lag and
      process times were much reduced when the synthetic FM22 medium was used for the
      inoculum compared with enriched buffered glycerol complex (BMGY) medium. The
      highest endoglucanase activity was obtained at 30 degrees C which was more than
      10 fold higher than that produced from shake flask. At 30 degrees C, the specific
      endoglucanase activity was dependent on culture pH and a higher specific activity
      was observed at pH 5.0 than at pH 6.0. The higher activity was likely due to
      lower rate of proteolysis, since a truncated protein species was apparent at pH
      6.0, but not pH 5.0. Thus, production of endoglucanase at 30 degrees C and pH 5.0
      is the optimal condition suitable for economical production in large scale. The
      combination of using synthetic FM22 medium for inoculum and proteolysis control
      by growth at lower pH could be applied for production of other recombinant
      proteins in P. pastoris.

PMID- 23548274
TI  - Impact of carbon source and variable nitrogen conditions on bacterial
      biosynthesis of polyhydroxyalkanoates: evidence of an atypical metabolism in
      Bacillus megaterium DSM 509.
AB  - Twenty bacterial strains were examined on their ability to produce
      polyhydroxyalkanoates (PHA) from different carbon sources under rich and depleted
      nitrogen conditions. Preliminary experiments with glucose as sole carbon source
      allowed to select PHA producing bacteria using FTIR spectroscopy. They were
      further tested with eight additional carbon substrates including organic, fatty
      acids or sugars. PHA content and monomer composition of four chosen strains
      (Pseudomonas putida mt-2, Bacillus megaterium DSM 90 and DSM 509, Corynebacterium
      glutamicum DSM 20137) were assessed by gas chromatography techniques for two
      cultural conditions: during growth phase on a mineral medium (MM) and after
      transfer of cells on a fresh MM without nitrogen (MM-N). For several carbon
      substrates, substantial amounts of PHA (up to 53% of the cell dry weight: CDW)
      were already obtained in MM for C. glutamicum DSM 20137 and the two B. megaterium
      strains; after transfer in MM-N, PHA contents remained constant except for B.
      megaterium DSM 509 where PHA production increased whatever the carbon source. P.
      putida mt-2 synthesized PHA under deprived nitrogen conditions. Highest PHA
      accumulation reached 48 and 77% of CDW with octanoic acid as substrate in B.
      megaterium DSM 90 and P. putida mt-2, respectively. Surprisingly, an atypical
      metabolic shift was observed for B. megaterium DSM 509 cultivated with nearly all
      unrelated carbon sources: whereas short chain length PHA (scl-PHA) were
      synthesized in MM, medium chain length PHA (mcl-PHA) were produced after transfer
      of cells into MM-N supplemented with the same substrate. 

PMID- 23548275
TI  - Causes and consequences of expectation trajectories: "high" on optimism in a
      public ballot initiative.
AB  - Although expectations are key theoretical antecedents of emotion and behavior,
      expectations are typically examined as static properties without deep
      consideration of their temporal dynamics. We surveyed residents of California
      over five time points, during the month preceding a public ballot initiative on
      cannabis legalization (California Proposition 19) and after the election, to
      examine both the causes and the consequences of residents' expectation
      trajectories regarding the vote's outcome. Our results point to the importance of
      changes in individuals' expectations over time. Specifically, well-informed
      voters were likely to lower their expectations regarding the measure's passage as
      the vote neared, in line with polling results, but being informed about the
      initiative had less impact on expectation trajectories among voters who favored
      the measure than among those who opposed it. Furthermore, supporters who
      maintained their optimism about the initiative's outcome over time were more
      likely to vote and were more disappointed following the measure's failure,
      compared with supporters who became more pessimistic. The findings suggest that
      temporal changes in people's optimism and expectations play a unique role in
      social behavior.

PMID- 23548276
TI  - Would an obese person whistle vivaldi? Targets of prejudice self-present to
      minimize appearance of specific threats.
AB  - How do targets of stigma manage social interactions? We built from a threat
      specific model of prejudice to predict that targets select impression-management
      strategies that address the particular threats other people see them to pose. We
      recruited participants from two groups perceived to pose different threats:
      overweight people, who are heuristically associated with disease and targeted
      with disgust, and Black men, who are perceived to be dangerous and targeted with
      fear. When stereotypes and prejudices toward their groups were made salient,
      overweight people (Studies 1 and 2) and Black men (Study 2) selectively
      prioritized self-presentation strategies to minimize apparent disease threat
      (wearing clean clothes) or physical-violence threat (smiling), respectively. The
      specific threat a group is seen to pose plays an important but underexamined role
      in the psychology of being a target of prejudice.

PMID- 23548277
TI  - Associations between locomotion score and kinematic measures in dairy cows with
      varying hoof lesion types.
AB  - During this study we explored the gait attributes commonly used in subjective
      locomotion scoring systems and use new technology to evaluate these gait
      attributes objectively on 60 Holstein lactating dairy cattle. Kinematic gait
      analysis more commonly used in sports and equine science was adapted for use on
      dairy cattle to assess stride characteristics, joint flexion, and spine posture
      in dairy cows with different lameness status. Cows that were lame had shorter
      stride length and had negative tracking distance compared with nonlame cattle.
      Lame cattle did not show any difference in spine posture when walking. Gait
      alterations were more evident in cows with sole ulcers, which showed considerable
      shortening of stride and had more negative tracking compared with cows with no
      hoof lesions. Cows with sole ulcers also showed significant shortening of the
      spine when walking than cows with no hoof lesions.

PMID- 23548278
TI  - Effect of genetic type and casein haplotype on antioxidant activity of yogurts
      during storage.
AB  - The aim of this work was to investigate the antioxidant activity of yogurt made
      from the milk of 2 breeds-Italian Brown and Italian Holstein-characterized by
      different casein haplotypes (alphaS1-, beta-, and kappa-caseins) during storage
      up to 15 d. The casein haplotype was determined by isoelectric focusing;
      antioxidant activity of yogurt was measured using 2,2'-azino-bis-(3
      ethylbenzothiazoline-6-sulfonic acid). The statistical analysis showed a
      significant effect of the studied factors. Antioxidant activity increased during
      storage of both yogurt types, but yogurt produced with Italian Brown milk showed
      higher antioxidant activity than those produced with Italian Holstein milk. A
      high scavenging activity was present in yogurts with the allelic combination of
      BB-A(2)A(2)-BB. The results of this study suggest that the genetic type and the
      haplotype make a significant contribution in the production of yogurts with high
      nutraceutical value.

PMID- 23548279
TI  - Relative bioavailability of soil-bound polychlorinated biphenyls in lactating
      goats.
AB  - Livestock may be exposed to organic pollutants via ingestion of contaminated
      matrices such as fodder or soil. The question on contribution of soil-bound
      polychlorinated biphenyls (PCB) to livestock exposure was not yet considered. The
      aim of this study was to assess the relative bioavailability of soil-bound PCB by
      assessing milk excretion of indicator PCB (I-PCB) after ingestion by goats of
      graded levels of PCB (mainly PCB forms 153, 180, and 138) in soil-contaminated
      feeds or in oil-contaminated feeds. Eight multiparous Alpine goats were grouped
      in 4 pairs on the basis of body weight and milk yield. In each pair, one goat was
      assigned to the soil feeds and the other one to the oil feeds. The experiment
      consisted of a 7-d adaptation period, followed by a 96-d exposure period. The
      exposure period was divided into 3 successive 32-d periods during which each goat
      received either 3 soil feeds or 3 oil feeds, distributed in increasing rank of
      contamination. During the last week of each 32-d period, milk from each goat was
      collected during 3 successive 24-h periods, stored at -20 degrees C, and freeze
      dried before analysis (extraction by accelerated solvent extraction, followed by
      gas chromatography-mass spectrometry analysis). Bioavailability of I-PCB from
      soil or spiked oil feeds was estimated by means of the slope-ratio method from I
      PCB concentration in milk in response to ingested I-PCB. Relative bioavailability
      was found to vary from 36 to 50% for PCB 118, 138, and 153 and it was 73% for PCB
      180. When considered globally, the response obtained with the I-PCB was estimated
      to 51%. Relative bioavailability was not established for PCB 52 and 101,
      compounds known to be readily cleared and showing low concentrations in milk. For
      PCB 28, no significant interaction was found between matrix and dose. This
      experiment reveals that PCB bound to soil are potentially liberated from soil
      during the digestive process and may undergo absorption, distribution,
      metabolism, and excretion. Thus, soil has to be considered as a risk matrix for
      ruminants and rearing practices in contaminated areas should strictly reduce the
      risk of soil ingestion by the ruminants.

PMID- 23548280
TI  - Milk fat globule membrane isolated from buttermilk or whey cream and their lipid
      components inhibit infectivity of rotavirus in vitro.
AB  - Milk fat is encapsulated in a milk fat globule membrane (MFGM) that contains
      bioactive glycoproteins and glycolipids. The MFGM inhibits infectivity of
      rotavirus (RV), activity that has been attributed to its glycoprotein and
      carbohydrate components. However, previous studies of proteins and
      oligosaccharides in the MGFM have not accounted for all the bioactivity
      associated with the complete MFGM. The lipid fraction of the MFGM accounts for
      half of its composition by weight, and we postulate that this fraction should be
      tested by itself to determine if it plays a role in antiviral activity. Herein,
      the anti-RV activity of an organic extract of MFGM was tested. Natural and whey
      buttermilk powders containing bovine MFGM enriched in polar lipids were prepared
      by microfiltration and supercritical fluid extraction treatment to reduce the
      triglyceride content of the powders. Lipid fractions were then extracted from the
      MFGM using both single- and dual-phase extraction methods. Whole MFGM and organic
      extracts were screened in MA-104 cells for anti-infective activity against a
      neuraminidase-sensitive rotavirus using a focus-forming unit assay. Dose
      dependent inhibition was observed for whole buttermilk and cheese whey MFGM
      against the rotavirus. In general, buttermilk MFGM exhibited greater RV
      percentage inhibition than cheese whey MFGM. Organic-soluble anti-RV compounds
      were identified in bovine MFGM. The most active fraction, isolated by dual-phase
      extraction and iatrobead chromatography, was free of proteins and highly
      nonpolar. Further separation of this fraction in a less polar solvent (30:1
      chloroform:methanol) resolved at least 5 lipid-containing compounds, which likely
      contribute to the anti-RV activity associated with bovine MFGM. In summary, lipid
      components associated with MFGM appear to contribute in large part to the anti-RV
      activity associated with the bovine MFGM.

PMID- 23548281
TI  - Effects of urea formaldehyde condensation polymer treatment of flaxseed on
      ruminal digestion and lactation in dairy cows.
AB  - Flaxseed is a potent source of the n-3 fatty acid alpha-linolenic acid (ALA), yet
      most ALA is lost during ruminal biohydrogenation when ground flaxseed is fed to
      ruminants. Heat processing and urea formaldehyde condensation polymer (UFCP)
      treatment of flaxseed were investigated as possible means of protecting ALA from
      ruminal degradation. Ground flaxseed (GF), heated ground flaxseed (HGF), or UFCP
      treated ground flaxseed (UFCPGF) were incubated for 0, 4, 8, and 12h in 4
      ruminally cannulated multiparous lactating Holstein cows. Compared with GF, HGF
      and UFCPGF decreased ruminal disappearance of dry matter, crude protein, and ALA.
      Pepsin-digestible protein remaining after 12h of ruminal incubation was greater
      for UFCPGF and HGF than for GF. Twenty-four lactating Holstein cows (207 +/- 37 d
      in milk, 668 +/- 66 kg of body weight, and 1.33 +/- 0.56 lactations) were then
      used in a randomized complete block design experiment with a basal feeding period
      to assess effects of flaxseed treatment on ALA enrichment of plasma and milk as
      well as lactational performance. No evidence existed that supplementation of HGF
      and UFCPGF affected dry matter intake, milk fat content, milk protein content, or
      energy-corrected milk yield, but UFCPGF marginally decreased milk yield compared
      with HGF. Plasma concentration of ALA was not affected by treatment.
      Concentrations of n-3 fatty acids and conjugated linoleic acids in milk fat were
      increased by UFCPGF relative to HGF, but ALA yield was not affected. Taken
      together, in situ results suggest that heat-treated flaxseed, with or without
      UFCP treatment, slowed ruminal disappearance of ALA. Feeding UFCP-treated
      flaxseed failed to alter ALA content of plasma or milk ALA yield relative to
      heating alone.

PMID- 23548282
TI  - Alkalinizing effect of NaHCO3 with and without glucose when administered orally
      to euhydrated neonatal dairy calves.
AB  - The use of oral rehydration solutions (ORS) is well established as an effective
      treatment to correct water-, electrolyte-, and acid-base balance in diarrheic
      calves. The main ingredients of a commercial ORS are Na, glucose, and
      alkalinizing agents, such as NaHCO3. Particular importance is attributed to the
      combination of glucose and Na at a specific ratio to optimize intestinal sodium,
      and thereby water uptake, through the sodium-glucose co-transport. Enhancing
      intestinal Na absorption by combining glucose and Na in an ORS has the potential
      to improve the alkalinizing effect of an ORS according the strong ion theory. The
      objective of this study was to investigate the effect of glucose on the
      alkalinizing effect of NaHCO3 when administered orally. Nine healthy neonatal
      Holstein-Friesian calves underwent 3 oral treatments with 2-L solutions of NaHCO3
      (150 mmol/L), glucose (300 mmol/L), and glucose + NaHCO3 (300 mmol/L + 150
      mmol/L, respectively) in randomized order. Arterial and venous blood was obtained
      before treatment and in 30-min intervals thereafter for blood gas analysis and
      determination of plasma protein and electrolyte concentrations. Urine was
      collected volumetrically to determine urine volume, osmolality, pH, net acid
      excretion, and renal Na excretion after treatment. Plasma volume changes were
      extrapolated from plasma protein concentration changes. Treatment and time
      effects were tested with repeated measures ANOVA. Only subtle differences between
      oral administration of NaHCO3, with and without glucose, were observed for the
      change of the standard HCO3 concentration relative to baseline. No differences in
      plasma Na, plasma volume expansion, renal Na, net base excretion, urine volume,
      or pH could be identified between animals treated orally with NaHCO3 with and
      without glucose. Similarly, no differences in blood glucose concentration, plasma
      volume expansion, urine volume, or renal glucose excretion were observed in the
      8h after treatment when comparing oral glucose treatment with and without NaHCO3.
      Our results indicate that combination of NaHCO3 with glucose in a hypertonic ORS
      only had a minor effect on the alkalinizing effect of NaHCO3, which is unlikely
      to be of clinical relevance. The combination of NaHCO3 and glucose neither
      improved Na, glucose, nor water absorption in euhydrated neonatal dairy calves,
      questioning the relevance of a specific ratio between Na and glucose in ORS for
      calves.

PMID- 23548283
TI  - Evaluating expansion strategies for startup European Union dairy farm businesses.
AB  - A stochastic whole-farm simulation model was used to examine alternative
      strategies for new entrant dairy farmers to grow and develop dairy farm
      businesses in the context of European Union (EU) milk quota abolition in 2015.
      Six alternative strategies were compared: remain static, natural growth
      expansion, waiting until after EU milk quota abolition to expand, a full-scale
      expansion strategy without milk quotas and not incurring super levy penalties, a
      full-scale expansion strategy with milk quotas and incurring super levy
      penalties, and once-a-day milking until EU milk quota abolition, followed by full
      scale expansion. Each discrete whole farm investment strategy was evaluated over
      a 15-yr period (2013-2027) using multiple financial stability and risk
      indicators, including overall discounted farm business profitability, net worth
      change, return on investment, and financial risk. The results of this study
      indicate that, although associated with increased risk, dairy farm expansion will
      ensure the future profitability of the farm business. Within the context of EU
      milk quotas until 2015, the most attractive expansion strategy is to increase cow
      numbers while avoiding super levy fines using once-a-day milking techniques,
      increasing to the full capacity of the dairy farm once milk quotas are removed.
      In contrast, the results also indicate that dairy farms that remain static will
      experience a significant reduction in farm profitability in the coming year due
      to production cost inflation. Cash flow deficits were observed during the initial
      year of expansion and, therefore, rapidly expanding dairy farm businesses require
      a significant cash reserve to alleviate business risk during the initial year of
      expansion. The results of this analysis also indicate that dairy farm businesses
      that expand using lower cost capital investments and avoid milk quota super levy
      fines significantly reduce the financial risks associated with expansion.

PMID- 23548284
TI  - Herd-level risk factors for hock injuries in freestall-housed dairy cows in the
      northeastern United States and California.
AB  - The aim of this study was to investigate the associations between management and
      facility design factors and the prevalence of hock injuries in high-producing
      dairy cows in 76 freestall herds in the northeastern United States (NE-US;
      Vermont, New York, Pennsylvania) and California (CA). One group of high
      production multiparous cows was monitored on each farm, and data on management,
      facility and stall design, and the conditions of the hocks were collected. Focal
      cows [n=38 +/- 3 (mean +/- standard deviation)] were evaluated for hock injuries
      using a 3-point scale (where 1=healthy and 3=evidently swollen or severe injury).
      Measures associated with the proportion (logit-transformed) of cows having
      injuries (score >= 2) or severe injuries (score=3) at the univariable level were
      submitted to multivariable general linear models. In NE-US, overall hock injuries
      increased with the percentage of stalls with fecal contamination [odds ratio
      (OR)=1.26; 95% confidence interval (CI)=1.02-1.54, for a 10% increase], and with
      the use of sawdust as bedding (OR=3.47; CI=1.14-10.62), and decreased with deep
      bedding (i.e., at least 10 cm depth of any type of bedding; OR=0.05; CI=0.02
      0.14), use of sand as bedding (OR=0.06; CI=0.02-0.15), bedding dry matter (DM) >=
      83.9% (OR=0.08; CI=0.03-0.20), and access to pasture during the dry period
      (OR=0.17; CI=0.05-0.53). When these variables were submitted to a multivariable
      model, the presence of deep bedding was the only factor that remained
      significant, explaining 54% of the variation in overall injuries. Severe hock
      injuries increased with the use of automatic scrapers (OR=2.29; CI=1.11-4.71) and
      the percentage of stalls with fecal contamination (OR=1.14; CI=1.00-1.31, for a
      10% increase), and decreased with sand bedding (OR=0.22; CI=0.10-0.49), deep
      bedding (OR=0.24; CI=0.11-0.52), bedding DM >= 83.9% (OR=0.28; CI=0.14-0.58), and
      access to pasture during the dry period (OR=0.42; CI=0.18-0.97). The final
      multivariable model, which explained 36% of the variation in severe hock
      injuries, included the use of automatic scrapers and deep bedding. In CA, stall
      stocking density (OR=1.41; CI=1.00-2.01, for a 10% increase) and poor bedding
      maintenance (OR=1.08; CI=1.01-1.16, for a 2.5-cm decrease in depth of deep-bedded
      stalls) were associated with an increase of overall and severe hock injuries,
      respectively. Deep-bedded and well-maintained stalls reduce the risk of hock
      injuries. Regional variation in risk factors for these injuries should be
      considered when formulating on-farm recommendations.

PMID- 23548285
TI  - Genome-wide association analysis identifies loci for left-sided displacement of
      the abomasum in German Holstein cattle.
AB  - Left-sided displacement of the abomasum (LDA) is one of the most common disorders
      of the digestive system in many dairy breeds and particularly in Holstein dairy
      cows. We performed a genome-wide association study for 854 German Holstein cows,
      including 225 cases and 629 controls. All cows were genotyped using the Illumina
      Bovine SNP50 BeadChip (Illumina Inc., San Diego, CA). After quality control of
      genotypes, a total of 36,226 informative single nucleotide polymorphisms (SNP)
      were left for analysis. We used a mixed linear model approach for a genome-wide
      association study of LDA. In total, 36 SNP located on 17 bovine (Bos taurus)
      chromosomes (BTA) showed associations with LDA at nominal -log10P-values >3.0.
      Two of these SNP, located on BTA11 at 46.70 Mb and BTA20 at 16.67 Mb, showed
      genome-wide significant associations with LDA at -log10P-values >4.6. Pathway
      analyses indicated genes involved in calcium metabolism and insulin-dependent
      diabetes mellitus to be factors in the pathogenesis of LDA in German Holstein
      cows.

PMID- 23548286
TI  - Associations of risk factors with somatic cell count in bulk tank milk on organic
      and conventional dairy farms in the United States.
AB  - In the past decade, the demand for organic agricultural products has increased
      rapidly in the United States and worldwide. Milk quality research is of major
      interest to both consumers and dairy farmers alike. However, scientific data on
      milk quality, herd management methods, and animal welfare on organic farms in the
      United States has been lacking before the research from this study. The objective
      of this study was to evaluate the association of bulk tank milk somatic cell
      count (SCC) with management characteristics on organic and conventional dairy
      farms in New York, Oregon, and Wisconsin. Data from similarly sized organic farms
      (n=192), conventional nongrazing farms (n=64), and conventional grazing farms
      (n=36) were collected at a single farm visit. Of the 292 farms visited, 290 bulk
      tank milk samples were collected. Overall, no difference in SCC was observed
      between the conventional and organic grazing systems. Two models were created to
      assess the effects of various management and herd characteristics on the
      logarithmic transformation of the SCC (LSCC), one using data from all herds and
      one using data from organic herds only. From the total herd model, more grain fed
      per cow per day was negatively associated with LSCC, whereas a positive bulk tank
      culture for Staphylococcus aureus and years that a farmer reported being in the
      dairy business were both positively associated with LSCC. In the organic herd
      model, a seasonal effect indicated that LSCC tended to increase in the summer and
      decrease in the winter. Grain fed per cow per day, the use of anionic salts in
      transition-cow diets, the use of gloves during milking, and regular use of a
      quarantine unit at milking were all negatively associated with LSCC. Similar to
      the total herd model, a Staph. aureus-positive bulk tank culture was positively
      associated with LSCC in the organic model. Standard plate count was also
      positively associated with LSCC in the organic model. Several variables that were
      associated with management using external resources were combined to create an
      external input score. In the total herd model, use of more external resources was
      negatively associated with LSCC. Conventional herds in the study tended to use
      more outside management resources than organic herds.

PMID- 23548287
TI  - Short communication: heat resistance of Escherichia coli strains in raw milk at
      different subpasteurization conditions.
AB  - A commonly applied treatment of raw milk to reduce bacterial loads is the short
      time application of heat at subpasteurization levels under continuous flow,
      generally referred to as thermization, because this method retains some of the
      beneficial properties of raw milk. In a previous study, Escherichia coli strains
      exhibiting increased thermotolerance were found, demanding investigations into
      their ability to survive thermization. Nine E. coli strains, including 4 Shiga
      toxin-producing E. coli (STEC) strains, were investigated for their reduction
      during a thermization treatment in raw milk using a pilot-plant pasteurizer to
      reflect typically applied commercial conditions. Six of the 9 E. coli strains,
      including the 4 STEC strains, were similarly inactivated at 60, 62.5, and 65
      degrees C, whereas increased thermotolerance was observed for 3 E. coli strains.
      All strains were reduced to <2 log10 at 60 and 62.5 degrees C within 25s. At 65
      degrees C, 6 of 9 E. coli strains were reduced by at least 5 log10 after 25s,
      whereas at 67.5 degrees C, such a reduction was observed for 8 strains. A much
      higher thermotolerance was found for E. coli strain FAM21805. For some E. coli
      strains, time-temperature combinations above 65 degrees C were required to obtain
      a substantial reduction during a thermization treatment.

PMID- 23548288
TI  - Metritis in dairy cows: risk factors and reproductive performance.
AB  - The objectives of this study were to assess the risk factors for metritis, its
      effects on milk yield and on reproductive performance, and the efficacy of
      ceftiofur therapy in Holstein dairy cows. Cows (n=303) from a commercial dairy
      herd in Argentina were studied. Cows were scored for body condition, and blood
      samples were collected on d -14, 7, 21, 31, 41, and 50 relative to parturition.
      Cows having a watery, purulent, or brown, and fetid vaginal discharge (VD) and
      rectal temperature <= 39.2 degrees C were diagnosed as having clinical metritis,
      and those having a similar VD and rectal temperature >39.2 degrees C were
      diagnosed as having puerperal metritis. Both clinical and puerperal metritis cows
      were randomly assigned to control (no treatment) or ceftiofur group (2.2mg/kg*3
      consecutive days). Cure was declared if clear VD was observed at 21 d in milk
      (DIM). Blood samples were analyzed for nonesterified fatty acids, beta
      hydroxybutyrate, and blood urea nitrogen using commercial kits, and for insulin
      like growth factor-1, insulin, and leptin by RIA. Data were analyzed with PROC
      MIXED, GENMOD, PHREG, and LIFETEST from SAS (SAS Institute Inc., Cary, NC). The
      risk for metritis increased with dystocia, retained fetal membranes, and dead
      calf [AOR (adjusted odds ratio)=2.58, 95% CI: 1.189-5.559], and as prepartum
      nonesterified fatty acids levels increased (AOR=1.001, 95% CI: 0.999-1.002).
      Conversely, risk decreased as prepartum insulin-like growth factor-1 increased
      (AOR=0.65, 95% CI: 0.349-1.219). Cows having either clinical or puerperal
      metritis produced less milk by 90 DIM than did healthy cows (2,236 +/- 172 vs.
      2,367 +/- 77 vs. 2,647 +/- 82 kg, respectively). Cows with puerperal metritis had
      lower risk for pregnancy by 100 DIM (AOR=0.189, 95% CI: 0.070-0.479) and a lower
      hazard rate for pregnancy by 150 DIM (hazard rate: 0.753, 95% CI: 0.621-0.911),
      and took longer to get pregnant (129 vs. 111 vs. 109 d, for puerperal metritis,
      clinical metritis, and healthy cows, respectively). Ceftiofur treatment was not
      associated with cure rate or milk yield but was related to increased risk for
      pregnancy at timed artificial insemination (AOR=2.688, 95% CI: 0.687-10.832), and
      for lower risk of reproductive cull (AOR=0.121, 95% CI: 0.014-1.066). In
      conclusion, abnormal calving and negative energy balance are associated with
      increased risk for metritis. Metritis, especially puerperal metritis, correlates
      with reduced milk production and poor reproductive performance. Finally, the
      likelihood for having a normal VD (indicative of cure) increased 2.6% for every
      day of increase in postpartum time and was 2 times higher for cows with clinical
      metritis than for those with puerperal metritis.

PMID- 23548289
TI  - Evaluation of milk powder quality by protein oxidative modifications.
AB  - The objective of the present research was to evaluate commercially available milk
      powders according to their protein oxidative modifications and antioxidant
      capacity, and to evaluate if these characteristics are related to physical
      quality parameters such as dispersibility or stability during storage. Fifteen
      commercially processed spray-dried milk powders were evaluated: 6 whole milk
      powders (WMP), 4 skim milk powders (SMP), and 5 infant formula powders (IFP).
      Protein oxidative status was measured as protein carbonyl (PC) content,
      dityrosine content, and extent of protein polymerization. The level of PC was
      slightly lower in SMP than in WMP, whereas IFP had more than twice as much PC as
      WMP (2.8 +/- 0.4, 2.1 +/- 0.2, and 6.5 +/- 1.3 nmol/mg of protein for WMP, SMP,
      and IFP, respectively). No differences were detected in dityrosine accumulation.
      Although all the possible pairs of parameters were tested for correlations, we
      found that 4 parameters were linked: PC, whey content, protein aggregate level,
      and dispersibility. After 9 mo of storage at -20 degrees C or room temperature,
      all milk samples were analyzed to evaluate changes in protein oxidative status
      (PC, dityrosine, and protein integrity) and related parameters. Compared with the
      initial condition, PC increased in all tested samples after 9 mo of storage at 
      20 degrees C or at room temperature. Stored milk powders had increased PC and
      decreased dispersibility compared with prestorage levels. Our results highlight
      the importance of protein oxidative status in milk powder and its relationship to
      other related quality parameters, such as protein integrity and dispersibility.
      Our findings suggest that the understanding of such relationships could help in
      developing quality differentiation for different types of milk powders in the
      product market.

PMID- 23548290
TI  - Development of protocols to evaluate in-line mastitis-detection systems.
AB  - This paper proposes and discusses a methodology to evaluate the performance of
      automated mastitis-detection systems with respect to their practical value on
      farm. The protocols are based on 3 on-farm requirements: (1) to detect cows with
      clinical mastitis promptly and accurately to enable timely and appropriate
      treatment, (2) to identify cows with high somatic cell count to manage bulk milk
      SCC levels, and (3) to report the mastitis infection status of cows at the end of
      lactation to support decisions on individual cow dry-cow therapy. Separate
      protocols for each requirement are proposed and discussed, including gold
      standards, evaluation tests, performance indicators, and performance targets.
      Aspects that require further research or clarification are identified. Actual
      field data are used as examples. Further debate is invited, the aim being to
      achieve international agreement on how to evaluate and report performance of
      different mastitis-detection technologies. Better performance information will
      allow farmers to compare different mastitis-detection systems sensibly and fairly
      before investing. Also, the use of evaluation protocols should help technology
      providers to refine current, or develop new, automated mastitis-detection
      systems. Such developments are likely to accelerate adoption of these systems,
      potentially leading to improved animal health, milk quality, and labor
      productivity.

PMID- 23548291
TI  - Short communication: peptide profiling in cheeses packed using different
      technologies.
AB  - Peptides released during the shelf life of cheeses packaged using 2 different
      technologies, vacuum packaging (VP) and modified-atmosphere packaging (MAP), were
      identified by on-line reverse phase-HPLC-tandem mass spectrometry. A total of 22
      peptides from the N-terminal domain of alphaS1-casein (CN) and 26 from beta-CN
      were identified, the latter more evenly distributed over the whole sequence.
      Peptides were monitored during the shelf life of these cheeses when stored at 4
      degrees C, revealing that the peptide profile changed significantly with the
      storage time. Qualitative differences between VP and MAP cheeses were only found
      for 3 alphaS1-CN peptides, which were absent in MAP cheeses. Semiquantitative
      analysis of peptides revealed some differences between cheeses packaged using
      different technologies. However, evolution of peptides during storage followed a
      common trend in both types of cheeses. In addition, the presence of certain
      peptides, which had been previously described because of their potential
      bioactivity, is illustrated. For instance, some of the identified peptides had
      been previously reported as antihypertensive peptides, such as peptide alphaS1-CN
      (1-9) or beta-CN f(201-209).

PMID- 23548292
TI  - Milk haptoglobin, milk amyloid A, and N-acetyl-beta-D-glucosaminidase activity in
      bovines with naturally occurring clinical mastitis diagnosed with a quantitative
      PCR test.
AB  - The associations between quantitative bacteriological results from a real-time
      PCR test and concentrations of acute-phase proteins (APP) and N-acetyl-beta-d
      glucosaminidase (NAGase) activity in milk in naturally occurring clinical
      mastitis were investigated. Milk APP concentrations and NAGase activity in
      clinical mastitis caused by different udder pathogens were studied. The
      associations between the severity of the clinical signs and concentrations of APP
      and NAGase activity were estimated. Milk samples from 281 cases of clinical
      mastitis were collected from 3 Estonian dairy farms and analyzed by PCR to
      identify pathogens. Twenty-seven samples out of 281 (9.6%) were PCR negative.
      Milk samples containing 4 or more bacterial species (n=28) were considered
      possibly contaminated and excluded from all further analyses. In total, 443
      bacterial identifications were made from the remaining 226 milk samples. A single
      bacterial species was detected in 68 samples (30.1%), 2 species were detected in
      99 samples (43.8%), and 3 species were detected in 59 (26.1%) samples. To
      determine the inflammatory response in the udder, the concentrations of milk
      amyloid A (MAA) and haptoglobin (Hp) and NAGase activity in the milk were
      analyzed. A significant positive association was found between the severity of
      the clinical signs and inflammatory markers in the milk. Milk amyloid A and Hp
      concentrations and NAGase activity were significantly higher in samples with
      large quantities of bacterial DNA from Escherichia coli or Streptococcus
      dysgalactiae compared with milk samples not containing those species. Large
      quantities of bacterial DNA from Trueperella pyogenes or Streptococcus uberis in
      the milk were associated with elevated concentrations of Hp and high NAGase
      activity, but not with increased MAA concentrations. Milk samples containing
      Corynebacterium bovis and coagulase-negative staphylococci had significantly
      lower concentrations of MAA and Hp and lower NAGase activity compared with
      samples where these species were not detected. It can be concluded that
      concentrations of APP and NAGase activity in the milk were associated with the
      quantity of bacterial DNA in the milk samples.

PMID- 23548293
TI  - Effect of storage temperature on crystal formation rate and growth rate of
      calcium lactate crystals on smoked Cheddar cheeses.
AB  - Previous studies have shown that storage temperature influences the formation of
      calcium lactate crystals on vacuum-packaged Cheddar cheese surfaces. However, the
      mechanisms by which crystallization is modulated by storage temperature are not
      completely understood. The objectives of this study were to evaluate the effect
      of storage temperature on smoked Cheddar cheese surfaces for (1) the number of
      discrete visible crystals formed per unit of cheese surface area; (2) growth rate
      and shape of discrete crystals (as measured by area and circularity); (3)
      percentage of total cheese surface area occupied by crystals. Three vacuum
      packaged, random weight (~300 g) retail samples of naturally smoked Cheddar
      cheese, produced from the same vat of cheese, were obtained from a retail source.
      The samples were cut parallel to the longitudinal axis at a depth of 10mm from
      the 2 surfaces to give six 10-mm-thick slabs, 4 of which were randomly assigned
      to 4 different storage temperature treatments: 1, 5, 10 degrees C, and weekly
      cycling between 1 and 10 degrees C. Samples were stored for 30 wk. Following the
      onset of visible surface crystals, digital photographs of surfaces were taken
      every other week and evaluated by image analysis for number of discrete crystal
      regions and total surface area occupied by crystals. Specific discrete crystals
      were chosen and evaluated biweekly for radius, area, and circularity. The entire
      experiment was conducted in triplicate. The effects of cheese surface, storage
      temperature, and storage time on crystal number and total crystal area were
      evaluated by ANOVA, according to a repeated-measures design. The number of
      discrete crystal regions increased significantly during storage but at different
      rates for different temperature treatments. Total crystal area also increased
      significantly during storage, at rates that varied with temperature treatment.
      Storage temperature did not appear to have a major effect on the growth rates and
      shapes of the individual crystals that were chosen for analysis. The data
      indicated that the effect of storage temperature was complex, likely involving
      solubility changes, the formation of d(-) and l(+) lactic acid, and the
      occurrence of syneresis, which in turn affected the number of crystal formation
      sites and total crystal area on the cheese surface.

PMID- 23548294
TI  - Characterization of Oaxaca raw milk cheese microbiota with particular interest in
      Lactobacillus strains.
AB  - The aim of this work was to identify and characterize lactobacilli strains from
      Mexican Oaxaca cheese. Twenty-seven lactobacilli isolated from Oaxaca cheese were
      identified at species level by 16S rRNA sequencing. Selected isolates were
      further characterized by ribotyping. Isolates were screened, among others, by
      acidifying capacity, antibiotic resistance, and activity against pathogens.
      Lactobacillus plantarum was predominant in Oaxaca cheese. The intraspecies
      variability of Lb. plantarum isolates was great. Multiple antibiotic resistances
      were observed. Eight isolates showed antimicrobial activity against the
      pathogenic species tested. Four Lb. plantarum strains showing low antibiotic
      resistance index, antimicrobial activity against enterotoxigenic Staphylococcus
      aureus and Listeria innocua stains, amine-negative decarboxylase activity, and
      resistance to NaCl and bile salt solutions, could be preselected to complete
      studies focused on designing a culture for use in pasteurized-milk Oaxaca cheese
      manufacturing.

PMID- 23548295
TI  - Identification of hepatic biomarkers for physiological imbalance of dairy cows in
      early and mid lactation using proteomic technology.
AB  - Identification of biomarkers for degree of physiological imbalance (PI), a
      situation in which physiological parameters deviate from normal, is needed to
      reduce disease risk and improve production and reproduction performance of cows.
      The objective was to describe the liver proteome in early and mid lactation for
      cows with different degrees of PI with a special focus on biomarkers and pathways
      involved in periparturient disease complexes. Twenty-nine cows in early [49 +/-
      22d in milk (DIM); n=14] and mid (159 +/- 39 DIM; n=15) lactation were nutrient
      restricted for 4d to increase PI by supplementing the ration with 60% wheat
      straw. Liver biopsies were collected -1 and 3d relative to restriction. Before
      restriction, an index for PI was calculated based on plasma nonesterified fatty
      acids, beta-hydroxybutyrate, and glucose concentrations. Within E and M cows, a
      subsets of 6 cow was classified as having either the greatest (PI) or least
      (normal; N) degree of PI and were used for isobaric tags for relative and
      absolute quantitation (iTRAQ)-based quantitative profiling in liver using liquid
      chromatography-tandem mass spectrometry. We identified pyruvate carboxylase and
      isocitrate dehydrogenase as potential hepatic biomarkers for PI for cows during
      early lactation and alcohol dehydrogenase-4 and methylmalonate-semialdehyde
      dehydrogenase for cows in mid lactation. This preliminary study identified new
      biomarkers in liver for PI and provided a better understanding of the differences
      in coping strategies used for cows in PI. Despite the small sample size
      (n=3/group), the results lay a foundation for future research focused on the
      usefulness of the hepatic biomarkers for predicting PI and thereby cows at risk
      for disease during lactation.

PMID- 23548296
TI  - Comparison of innate immune responses and somatotropic axis components of
      Holstein and Montbeliarde-sired crossbred dairy cows during the transition
      period.
AB  - Objectives were to compare parameters related to innate immune responses and
      somatotropic axis of Holstein (HO) and Montbeliarde (MO)-sired crossbred cows
      during the transition from late gestation to early lactation. Cows (40 HO and 47
      MO-sired crossbred) were enrolled in the study 45d before expected calving date
      (study d 0=calving). Polymorphonuclear leukocytes (PMNL) isolated from blood
      samples collected weekly from study d -7 to 21 and on study d 42 were used for
      determination of percentage of PMNL positive for phagocytosis (PA+) and oxidative
      burst (OB+), intensity of PA and OB, percentage of PMNL expressing CD18 (CD18+)
      and L-selectin (LS+), and intensity of CD18 and LS expression. Blood was sampled
      weekly from study d -7 to 14 and on study d 28, 42, and 56 for determination of
      insulin, growth hormone (GH), leptin, and insulin-like growth factor (IGF)-1
      concentrations. Blood sampled weekly from study d -14 to 21 and on study d 42 was
      used to determine cortisol concentration. Liver biopsies were performed on study
      d -14, 7, 14, and 28 for determination of mRNA expression for insulin receptor B
      (IRB), total GH receptor (GHRtot), GHR variant 1A (GHR1A), and IGF-1. Data were
      analyzed by ANOVA for repeated measures or by ANOVA using the GLM procedure of
      SAS (SAS Institute Inc., Cary, NC). Intensity of CD18 expression was greater in
      PMNL from crossbred cows compared with PMNL from HO cows [1,482.1 +/- 82.3 vs.
      1,286.6 +/- 69.8 geometric mean fluorescence intensity (GMFI)]. Furthermore,
      among HO cows, the percentage of PA+ PMNL on study d -7 (64.4 +/- 5.2%) tended to
      be greater than on study d 0 (57.1 +/- 5.1%), but no differences in percentage of
      PA+ PMNL between study d -7 and 0 were observed in crossbred cows. Similarly,
      intensity of PA in PA+ PMNL from HO cows decreased from study d -7 to 0 (4,750.6
      +/- 1,217.0 vs. 1,964.7 +/- 1,227.9 GMFI), but no changes in intensity of PA in
      PA+ PMNL from crossbred cows were observed. On study d 0, intensity of PA tended
      to be reduced in PA+ PMNL from HO cows compared with PA+ PMNL from crossbred cows
      (1,964.7 +/- 1,227.9 vs. 4,688.1 +/- 1,271.8 GMFI). Concentrations of GH (7.4 +/-
      0.4 vs. 5.1 +/- 0.4 ng/mL) and cortisol (9.5 +/- 0.8 vs. 7.1 +/- 0.8 ng/mL) were
      greater for HO than for crossbred cows. Crossbred cows had improved innate immune
      responses compared with HO cows, as determined by a lack of decrease in intensity
      of PA on the day of calving, which may result in improved health. Furthermore, HO
      cows appeared to be less sensitive to the negative feedback of IGF-1 on GH
      secretion because cows from both breeds had similar IGF-1 concentrations but MO
      sired crossbred cows had greater GH concentrations.

PMID- 23548297
TI  - Modeling the growth of Listeria monocytogenes in mold-ripened cheeses.
AB  - This study presents possible applications of predictive microbiology to model the
      safety of mold-ripened cheeses with respect to bacteria of the species Listeria
      monocytogenes during (1) the ripening of Camembert cheese, (2) cold storage of
      Camembert cheese at temperatures ranging from 3 to 15 degrees C, and (3) cold
      storage of blue cheese at temperatures ranging from 3 to 15 degrees C. The
      primary models used in this study, such as the Baranyi model and modified
      Gompertz function, were fitted to growth curves. The Baranyi model yielded the
      most accurate goodness of fit and the growth rates generated by this model were
      used for secondary modeling (Ratkowsky simple square root and polynomial models).
      The polynomial model more accurately predicted the influence of temperature on
      the growth rate, reaching the adjusted coefficients of multiple determination
      0.97 and 0.92 for Camembert and blue cheese, respectively. The observed growth
      rates of L. monocytogenes in mold-ripened cheeses were compared with simulations
      run with the Pathogen Modeling Program (PMP 7.0, USDA, Wyndmoor, PA) and ComBase
      Predictor (Institute of Food Research, Norwich, UK). However, the latter
      predictions proved to be consistently overestimated and contained a significant
      error level. In addition, a validation process using independent data generated
      in dairy products from the ComBase database (www.combase.cc) was performed. In
      conclusion, it was found that L. monocytogenes grows much faster in Camembert
      than in blue cheese. Both the Baranyi and Gompertz models described this
      phenomenon accurately, although the Baranyi model contained a smaller error.
      Secondary modeling and further validation of the generated models highlighted the
      issue of usability and applicability of predictive models in the food processing
      industry by elaborating models targeted at a specific product or a group of
      similar products.

PMID- 23548298
TI  - Development of a genetic evaluation for body condition score for Canadian
      Holsteins.
AB  - Valacta (Sainte-Anne-de-Bellevue, Quebec, Canada) is the Canadian Dairy Herd
      Improvement organization responsible for milk recording in Quebec and Atlantic
      provinces. Up to 14 first-lactation body condition score (BCS) records were
      collected per cow (average of 2.5 records per cow), allowing the trait to be
      described by a random regression animal model so that animals could be ranked by
      the shape of their BCS curve. However, Valacta's BCS are available from Quebec
      herds only and the long-term objective of this research is to develop a
      nationwide genetic evaluation of sires and cows for BCS. Alternatively, Holstein
      Canada (Brantford, Ontario, Canada) collects type trait records nationwide,
      primarily for first-lactation cows. Holstein Canada typically collects a single
      record per trait, so that selection for Holstein Canada BCS would be based on
      overall BCS level rather than the shape of the BCS curve. Several different
      methods of genetically evaluating Valacta's BCS were investigated, including
      consideration of average BCS level across lactation, the amount of fluctuation in
      the BCS curve during lactation, and combinations of BCS level and BCS
      fluctuation. Sires with >= 25 daughters were compared (as opposed to comparing
      cows) because their BCS estimated breeding values (EBV) are based on more
      information, and so should be more reliable. Of the different methods of
      calculating Valacta BCS EBV, ranking bulls based on overall BCS level gave the
      best results in that their daughter phenotypic BCS curves showed limited loss in
      early lactation BCS and replenished condition by the end of lactation. Whereas
      Valacta's BCS were analyzed using a random regression animal model, Holstein
      Canada only needs to collect 1 BCS record per cow at classification and the
      resulting BCS EBV was strongly correlated with Valacta's BCS EBV. Furthermore,
      because Holstein Canada's BCS are collected nationally and Valacta's BCS are not,
      a national genetic evaluation for Holstein Canada's BCS is more convenient. The
      results of this study do not eliminate the possibility of a genetic evaluation of
      BCS as a longitudinal trait, but indicate that other methods of calculating
      Valacta BCS EBV should be explored. Until that time, genetically evaluating
      Holstein Canada's BCS is simple, easily implemented, and may be effective in
      altering the level and shape of the genetic BCS curve.

PMID- 23548299
TI  - Genetic and environmental information in goat milk Fourier transform infrared
      spectra.
AB  - Fourier transform infrared (FTIR) spectroscopy is often used in prediction of
      major milk components in genetic evaluation of dairy animals. Until now genetic
      variability of goat milk FTIR spectra has only been known indirectly through
      their contribution to the major milk components. In this study, genetic and
      environmental components of goat milk FTIR spectra were examined directly. A data
      set containing 83,858 milk FTIR spectral observations belonging to 29,320
      Norwegian dairy goats of 271 herds was used for the study. Principal components
      analysis was applied on both unprocessed and preprocessed spectral data, and new
      traits (latent traits) were defined because a multitrait analysis of all spectral
      variables for variance components could not be done. Eight and 7 latent
      variables, explaining approximately 99% of the total unprocessed and preprocessed
      spectral variation, respectively, were kept from the principal components
      analysis for genetic analysis. Genetic and environmental variance components were
      estimated for the latent traits using restricted maximum likelihood. Genetic-to
      total phenotypic variance ratios (heritabilities) of the latent traits were
      between 0.011 and 0.285 for the unprocessed spectra and between 0.135 and 0.262
      for the preprocessed spectra. The estimated variance components for the latent
      traits were back transformed to the spectral variables. Heritabilities of these
      spectral variables ranged from 0.018 to 0.408 and variance ratios of the
      permanent environmental effects of goats were between 0.002 and 0.184 of the
      phenotypic spectral variation. High-to-moderate heritabilities were observed in
      particular in spectral regions related to major milk components (fat, lactose,
      and protein): between 1,030 and 1,300 cm(-1), 1,500 and 1,600 cm(-1), 1,700 and
      1,800 cm(-1), and 2,800 and 3,000 cm(-1). Our results confirmed that a
      substantial amount of genetic variation exists in goat milk FTIR spectra. Not all
      spectral variations are of genetic origin; some FTIR regions are highly
      influenced by herd test-day variation. The study also pointed out the possibility
      of using FTIR spectra as a monitoring tool in herd management.

PMID- 23548300
TI  - Applicability of day-to-day variation in behavior for the automated detection of
      lameness in dairy cows.
AB  - Lameness is a major problem in modern dairy husbandry and has welfare
      implications and other negative consequences. The behavior of dairy cows is
      influenced by lameness. Automated lameness detection can, among other methods, be
      based on day-to-day variation in animal behavior. Activity sensors that measure
      lying time, number of lying bouts, and other parameters were used to record
      behavior per cow per day. The objective of this research was to develop and
      validate a lameness detection model based on daily activity data. Besides the
      activity data, milking data and data from the computerized concentrate feeders
      were available as input data. Locomotion scores were available as reference data.
      Data from up to 100 cows collected at an experimental farm during 23 mo in 2010
      and 2011 were available for model development. Behavior is cow-dependent, and
      therefore quadratic trend models were fitted with a dynamic linear model on-line
      per cow for 7 activity variables and 2 other variables (milk yield per day and
      concentrate leftovers per day). It is assumed that lameness develops gradually;
      therefore, a lameness alert was given when the linear trend in 2 or more of the 9
      models differed significantly from zero in a direction that corresponded with
      lameness symptoms. The developed model was validated during the first 4 mo of
      2012 with almost 100 cows on the same farm by generating lameness alerts each
      week. Performance on the model validation data set was comparable with
      performance on the model development data set. The overall sensitivity
      (percentage of detected lameness cases) was 85.5% combined with specificity
      (percentage of nonlame cow-days that were not alerted) of 88.8%. All variables
      contributed to this performance. These results indicate that automated lameness
      detection based on day-to-day variation in behavior is a useful tool for dairy
      management.

PMID- 23548301
TI  - The effect of starch-, fiber-, or sugar-based supplements on nitrogen utilization
      in grazing dairy cows.
AB  - Nitrogen utilization in grazing cows is often low due to high concentrations of
      rapidly soluble and degradable protein in the pasture-based diet. Broadly,
      opportunities to improve N utilization lie in either reducing the amount of N
      consumed by the animal, or incorporating more N into milk protein. The goal of
      this study was to compare the relative importance of dietary N intake and
      productive N output for improving N utilization in grazing cows fed either starch
      , fiber-, or sugar-based supplements. Also, the Cornell Net Carbohydrate and
      Protein System (CNCPS; Cornell University, Ithaca, NY) was evaluated as a tool to
      assess cow performance and improve N utilization in pasture-based systems. Eighty
      five cows were randomly assigned to 1 of 5 treatments at parturition (17 cows per
      treatment). Treatments consisted of a pasture-only control and pasture with a
      starch- (St and StN), fiber- (FbN), or a sugar-based supplement. The StN and FbN
      treatments contained additional dietary N. Diets were formulated using the CNCPS
      to supply similar levels of dietary metabolizable energy, but differing levels of
      dietary N and metabolizable protein. Nitrogen utilization ranged from 22 to 26%
      across the 5 groups. Cows fed the St diet had the lowest levels of milk urea N,
      blood urea N, and urinary N excretion and had the highest productive N output
      (149 g/d). Cows fed the FbN treatment had similar productive N output (137 g/d)
      and consumed approximately 100g/d more dietary N than the St treatment, resulting
      in greater urinary N excretion. Although milk protein yield was moderately
      greater in the St treatment, quantitatively the difference in N intake (100g/d)
      had the greatest effect on N utilization and suggests that controlling dietary N
      intake should be the first priority when attempting to improve N utilization in
      grazing cows. No effect was observed of supplementing pasture-fed cattle with
      sugar on production or N utilization under the conditions of this experiment.
      Predictions of metabolizable energy and protein availability for milk yield from
      the CNCPS were similar to actual milk yield for all treatments. Model-predicted N
      utilization and excretion reflected the trends observed in the measured data and
      suggests that the CNCPS can be a useful tool for formulating and evaluating diets
      to improve N utilization in pasture-based systems.

PMID- 23548302
TI  - Invited review: reduced milking frequency: milk production and management
      implications.
AB  - Most dairy cows throughout the world are milked twice daily. In intensive
      dairying systems, however, it is not uncommon to increase milking frequency to
      between 3 and 6 times daily to increase milk production. Reducing milking
      frequency is much less common; however, once-daily milking of dairy cows,
      practiced either strategically during certain parts of the lactation or for the
      entire lactation, is not uncommon in key dairying countries where less emphasis
      is placed on milk production per cow. The practice fits well with more extensive
      dairy production systems, particularly those based on grazed pasture. A feature
      of once-daily milking is that it reduces milk yield by approximately 22%,
      depending on stage of lactation, breed, and parity, and it may adversely affect
      lactation length and persistency. However, it can offer several positive farm
      management options, especially related to labor requirements and farm working
      expenses. In addition, it may provide a tool to better manage the metabolism and
      energy balance of cows during early lactation or during periods of pasture
      deficit, and it may help to improve reproductive performance and animal health
      and welfare. Once-daily milking, representing one extreme of the mammary function
      spectrum, has attracted considerable research interest over the years.
      Consequently, substantial scientific information is available on its effects on
      mammary function, at both the physiological and molecular levels. This review
      focuses instead on the management of the cow milked once daily, covering the
      production response in relation to breed, stage of lactation, and parity, and its
      effect on energy status, reproduction, health and welfare, as well as on milk
      composition and processability.

PMID- 23548303
TI  - Short communication: phenotypic and genetic diversity of wild Lactococcus lactis
      isolated from traditional Pecorino cheeses of Tuscany.
AB  - Wild Lactococcus lactis isolates from traditional Pecorino cheeses in 4 regions
      of Tuscany were isolated and characterized to evaluate the diversity of
      autochthonous lactococci. Sixty strains of Lactococcus were clustered by the
      results of carbohydrate utilization and diagnostic enzyme activity. Twenty-one
      unique strains were then chosen for characterization of salt and temperature
      tolerance, as well as acidification and proteolytic activity in milk. Genetic
      analysis of these strains was performed via 16S ribosomal DNA sequencing and
      multilocus sequence typing (MLST) to elucidate diversity relative to their
      location of origin. Phylogenetic analysis showed distinct clustering by region
      within organism subspecies, and phenotypic properties demonstrated concomitant
      trends. Multilocus sequence typing thus allowed for the regional distinction of
      isolates separate from those of previous works, supporting the concept that
      distinctive regional qualities of cheeses are strongly influenced by microbial
      ecology.

PMID- 23548304
TI  - Direct and maternal genetic relationships between calving ease, gestation length,
      milk production, fertility, type, and lifespan of Holstein-Friesian primiparous
      cows.
AB  - As the emphasis in cattle breeding is shifting from traits that increase income
      toward traits that reduce costs, national breeding indices are expanding to
      include functional traits such as calving ease (CE). However, one issue is the
      lack of knowledge of genetic relationships between CE and other dairy traits. The
      same can be said about gestation length (GL), a potential novel selection trait
      with considerable heritabilities and possible genetic relationships with the
      calving process. This study aimed to estimate the genetic relationships between
      CE, GL, and other dairy traits of interest using a national data set of 31,053
      primiparous cow performance records, as well as to separate direct and maternal
      genetic effects. Chosen dairy traits included fertility (calving interval, days
      to first service, nonreturn rate after 56 d, number of inseminations per
      conception), milk production (milk yield at d 110 in milk, accumulated 305-d milk
      yield, accumulated 305-d fat yield, accumulated 305-d protein yield), type (udder
      depth, chest width, rump width, rump angle, mammary composition, stature, body
      depth), and lifespan traits (functional days of productive life). To allow the
      separation of direct and maternal genetic effects, a random sire of the calf
      effect was included in the multi-trait linear trivariate sire models fitted using
      ASReml. Significant results showed that easily born individuals were genetically
      prone to high milk yield and reduced fertility in first lactation. Difficult
      calving primiparous cows were likely associated with being high-producing, wide
      and deep animals, with a reduced ability to subsequently conceive. Individuals
      that were born relatively early were associated with good genetic merit for milk
      production. Finally, individuals carrying their offspring longer were genetically
      associated with being wide and large animals that were themselves born relatively
      early. The study shows that it is feasible and valuable to separate direct and
      maternal effects when estimating genetic correlations between calving and other
      dairy traits. Furthermore, gestation length is best used as an indicator trait
      for lowly heritable calving traits, rather than as a novel selection trait. As
      estimated direct and maternal genetic correlations differ, we can conclude that
      genetic relationships between CE, GL, and traits of interest are present, but
      caution is required if these traits are implemented in national breeding indices.

PMID- 23548305
TI  - Oral administration of Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1
      suppresses inflammation by decreasing interleukin-6 responses in a murine model
      of atopic dermatitis.
AB  - The oral intake of Lactobacillus spp. can provide beneficial effects to the host
      by modulating the immune response. Atopic dermatitis (AD) is an allergic
      inflammatory disease mediated by various immune responses. In this study, we
      examined the effect of a Lactobacillus strain, Lactobacillus delbrueckii ssp.
      bulgaricus OLL1073R-1 (OLL1073R-1), on AD development in a murine model of AD
      that was developed by the topical application of mite antigen in NC/Nga mice. The
      oral intake of heat-killed OLL1073R-1 cells inhibited both the development of
      dermatitis and the elevation of an acute inflammation marker, serum amyloid A.
      Another bacterial strain, Lactobacillus rhamnosus OLL2984, exerted no inhibitory
      effects on dermatitis. The oral intake of heat-killed OLL1073R-1 cells also
      attenuated secretion of IL-6 from lymph node cells in response to mite antigen
      and reduced IL-6 levels in inflamed tissues, such as auricles. Production of IFN
      gamma or IL-4 was not influenced by OLL1073R-1 intake. We also found that
      inhibition of IL-6 signaling by gp130-Fc (a fusion protein consisting of the
      extracellular portion of glycoprotein 130 fused to the Fc region of human IgG1)
      markedly decreased the severity of dermatitis in NC/Nga mice. Moreover, secretion
      of IL-6 by lymph node cells was augmented in NC/Nga mice compared with that in
      BALB/c mice. These results indicate that IL-6 plays an essential role in the
      development of dermatitis in the NC/Nga mouse model of AD, and that OLL1073R-1
      inhibits dermatitis, at least in part, by suppressing the IL-6 response.

PMID- 23548306
TI  - Effect on quarter milk somatic cell count and antimicrobial susceptibility of
      Staphylococcus rostri causing intramammary infection in dairy water buffaloes.
AB  - In many parts of the world, coagulase-negative staphylococci (CNS) are the
      predominant cause of intramammary infections (IMI) in dairy cows and in water
      buffaloes, as well. A longitudinal field study was carried out on one well
      managed dairy water buffalo herd to determine the prevalence and distribution of
      CNS and a recently described CNS-species, Staphylococcus rostri, in milk samples
      to explore its relevance for buffaloes' udder health throughout lactation, and to
      gain insight into the susceptibility of the latter species toward commonly used
      antimicrobials. Twice weekly quarter milk samples from a cohort of 11 lactating
      water buffaloes were collected over an 8-mo period. The CNS (n=109; 76.2% of all
      culture-positive samples) were the predominant pathogens causing IMI, followed by
      Corynebacterium bovis (n=11; 7.6%) and Streptococcus spp. (n=9; 6.2%) other than
      Stretococcus uberis (n=2; 1.4%). Thirty-seven hemolytic staphylococci suspected
      to be Staphylococcus aureus were further differentiated using transfer DNA
      intergenic spacer-PCR and rpoB-gene sequencing because they were coagulase
      negative. Thirty-three of those isolates were identified as Staph. rostri,
      whereas 2 others were identified as Staphylococcus epidermidis. None of the
      Staph. rostri isolates displayed resistance to the antimicrobial agents tested.
      Mean quarter milk somatic cell count (qSCC) of all samples collected throughout
      lactation was 20,970 cells/mL. The qSCC at sampling of quarters infected with
      Staph. rostri (34,466 cells/mL) and CNS other than Staph. rostri (34,813
      cells/mL) were significantly higher than the qSCC of noninfected quarters (20,287
      cells/mL), yet not significantly different from each other. These findings
      provide novel insight into the prevalence and distribution, antimicrobial
      susceptibility, and relevance of Staph. rostri compared with other CNS species
      causing IMI in water buffaloes. Further studies are needed to pinpoint the
      relevance, niches, and transmission routes of Staph. rostri, as well as other CNS
      in water buffaloes.

PMID- 23548307
TI  - Allergen chip diagnosis for soy-allergic patients: Gly m 4 as a marker for severe
      food-allergic reactions to soy.
AB  - BACKGROUND: Gly m 5 and Gly m 6 are known to induce severe reactions in soy
      allergic patients. For birch pollen (BP)-allergic patients, the Bet v 1
      homologous allergen Gly m 4 is also a potential trigger of generalized severe
      reactions upon soy consumption. Therefore, reliable component-resolved diagnosis
      of soy allergy is needed. METHODS: IgE reactivity from sera of 20 patients from a
      BP environment with reported soy allergy was assessed. Skin prick tests (SPT)
      with BP and soy drink were performed. Specific IgE for BP, soy, Bet v 1 and Gly m
      4 was analyzed by ImmunoCAP. In addition, ISAC microarray profiling was
      performed. RESULTS: Nineteen of 20 patients were BP allergic (positive SPT and/or
      CAP results for BP extract and Bet v 1). Eighteen soy-allergic patients were
      tested positive with soy drink in SPT. Soy CAP results were negative in the
      majority of tests (15/20), whereas 19/20 sera had specific IgE to Gly m 4. In the
      microarray approach, 14/20 sera displayed Gly m 4-specific IgE, the additional 6
      sera had IgE levels below 0.3 ISAC standardized units. The BP-negative serum had
      Gly m 5- and Gly m 6-specific IgE which correlated with positive soy ImmunoCAP.
      CONCLUSIONS: Soy sensitization detected by SPT and Gly m 4 ImmunoCAP were in good
      qualitative agreement with ISAC results. Soy ImmunoCAP was only specific for Gly
      m 5 and Gly m 6 sensitization. Gly m 4 ImmunoCAP has a higher sensitivity than
      ImmunoCAP ISAC. In this patient cohort, Gly m 4 sensitization was linked to the
      development of severe and generalized allergic reactions upon soy consumption.

PMID- 23548309
TI  - Ferric citrate hydrate, a new phosphate binder, prevents the complications of
      secondary hyperparathyroidism and vascular calcification.
AB  - BACKGROUND/AIMS: Ferric citrate hydrate (JTT-751) is being developed as a
      treatment for hyperphosphatemia in chronic kidney disease patients, and shows
      serum phosphorus-reducing effects on hyperphosphatemia in hemodialysis patients.
      We examined whether JTT-751 could reduce phosphorus absorption in normal rats and
      prevent the progression of ectopic calcification, secondary hyperparathyroidism
      and bone abnormalities in chronic renal failure (CRF) rats. METHODS: Normal rats
      were fed a diet containing 0.3, 1 or 3% JTT-751 for 7 days. The effects of JTT
      751 on phosphorus absorption were evaluated with fecal and urinary phosphorus
      excretion. Next, a CRF model simulating hyperphosphatemia was induced by feeding
      rats a 0.75% adenine diet. After 21 days of starting the adenine diet feeding, 1
      or 3% JTT-751 was administered for 35 days by dietary admixture. The serum
      phosphorus levels and mineral parameters were measured. Calcification in the
      aorta was examined biochemically and histopathologically. Hyperparathyroidism and
      bone abnormalities were evaluated by histopathological analysis of the
      parathyroid and femur, respectively. RESULTS: In normal rats, JTT-751 increased
      fecal phosphorus excretion and reduced phosphorus absorption and urinary
      phosphorus excretion. In CRF rats, JTT-751 reduced serum phosphorus levels, the
      calcium-phosphorus product and calcium content in the aorta. Serum intact
      parathyroid hormone levels and the incidence and severity of parathyroid
      hyperplasia were also decreased. JTT-751 reduced femoral bone fibrosis, porosity
      and osteoid formation. CONCLUSIONS: JTT-751 could bind with phosphate in the
      gastrointestinal tract, increase fecal phosphorus excretion and reduce phosphorus
      absorption. JTT-751 could prevent the progression of ectopic calcification,
      secondary hyperparathyroidism and bone abnormalities in rats.

PMID- 23548308
TI  - Molecular architecture of the human protein deacetylase Sirt1 and its regulation
      by AROS and resveratrol.
AB  - Sirtuins are NAD+-dependent protein deacetylases regulating metabolism, stress
      responses and ageing processes. Among the seven mammalian Sirtuins, Sirt1 is the
      physiologically best-studied isoform. It regulates nuclear functions such as
      chromatin remodelling and gene transcription, and it appears to mediate
      beneficial effects of a low calorie diet which can partly be mimicked by the
      Sirt1 activating polyphenol resveratrol. The molecular details of Sirt1 domain
      architecture and regulation, however, are little understood. It has a unique N
      terminal domain and CTD (C-terminal domain) flanking a conserved Sirtuin
      catalytic core and these extensions are assumed to mediate Sirt1-specific
      features such as homo-oligomerization and activation by resveratrol. To analyse
      the architecture of human Sirt1 and functions of its N- and C-terminal
      extensions, we recombinantly produced Sirt1 and Sirt1 deletion constructs as well
      as the AROS (active regulator of Sirt1) protein. We then studied Sirt1 features
      such as molecular size, secondary structure and stimulation by small molecules
      and AROS. We find that Sirt1 is monomeric and has extended conformations in its
      flanking domains, likely disordered especially in the N-terminus, resulting in an
      increased hydrodynamic radius. Nevertheless, both termini increase Sirt1
      deacetylase activity, indicating a regulatory function. We also find an unusual
      but defined conformation for AROS protein, which fails, however, to stimulate
      Sirt1. Resveratrol, in contrast, activates the Sirt1 catalytic core independent
      of the terminal domains, indicating a binding site within the catalytic core and
      suggesting that small molecule activators for other isoforms might also exist. 

PMID- 23548310
TI  - Attitudes and compliance with research requirements in OB/GYN residencies: a
      national survey.
AB  - BACKGROUND/AIMS: The Accreditation Council for Graduate Medical Education (ACGME)
      requires that all Ob/Gyn residents accomplish scholarly activity. We hypothesize
      resident productivity is poor. METHODS: This was a web-based two-survey study
      using SurveyMonkey(r). Surveys queried both program directors and residents
      regarding their adherence to ACGME guidelines. All 233 accredited Ob/Gyn programs
      were targeted. RESULTS: 70 program directors responded (30.4%). The majority
      (99%) felt research was a goal of their program and stated their residents are
      taught to read current literature (99%), design basic studies (99%), and
      interpret simple statistics (89%). 17% (53/313) of the residents did not agree
      that their training environment promoted research, 25% did not feel comfortable
      discussing basic study designs, and 54% did not feel comfortable interpreting
      basic statistics. Urban programs demonstrated improved resident attitudes toward
      research (p = 0.025), better research environments (p = 0.007) and curricula (p =
      0.001) compared to rural programs. Furthermore, residents intending to pursue an
      academic career were more likely to be working with a research mentor (p =
      0.038). CONCLUSION: The ACGME clearly delineates residency research requirements.
      A dichotomy exists between program director perception and resident compliance.
      Notwithstanding, it is reassuring that the majority of programs appear to promote
      scholarly activity and provide necessary support.

PMID- 23548311
TI  - Nitric oxide affects salt-induced changes in free amino acid levels in maize.
AB  - It was assumed that salt-induced redox changes affect amino acid metabolism in
      maize (Zea mays L.), and this influence may be modified by NO. The applied NaCl
      treatment reduced the fresh weight of shoots and roots. This decrease was smaller
      after the combined application of NaCl and an NO-donor ((Z)-1-[N-(2-aminoethyl)-N
      (2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, DETA/NO) in the shoots, while it
      was greater after simultaneous treatment with NaCl and nitro-L-arginine (L-NNA,
      inhibitor of NO synthesis) in the roots. The quantum yield efficiency of
      photosystem II was not influenced by the treatments. NaCl had a significant
      effect on the redox environment in the leaves as it was shown by the increase in
      the amount of glutathione disulphide and in the redox potential of the
      glutathione/glutathione disulphide redox pair. This influence of NaCl was
      modified by DETA/NO and L-NNA. Pharmacological modification of NO levels affected
      salt-induced changes in both the total free amino acid content and in the free
      amino acid composition. NaCl alone increased the concentration of almost all
      amino acids which effect was strengthened by DETA/NO in the case of Pro. L-NNA
      treatment resulted in a significant increase in the Ala, Val, Gly and Tyr
      contents. The Ile, Lys and Val concentrations rose considerably after the
      combined application of NaCl and DETA/NO compared to NaCl treatment alone in the
      recovery phase. NaCl also increased the expression of several genes related to
      the amino acid and antioxidant metabolism, and this effect was modified by
      DETA/NO. In conclusion, modification of NO levels affected salt-induced,
      glutathione-dependent redox changes and simultaneously the free amino acid
      composition and the level of several free amino acids. The observed much higher
      Pro content in plants treated with both NaCl and DETA/NO during recovery may
      contribute to the protective effect of NO against salt stress.

PMID- 23548313
TI  - E-cadherin and beta-catenin expression during urothelial carcinogenesis induced
      by N-butyl-N-(4-hydroxybutyl) nitrosamine in mice.
AB  - BACKGROUND: E-cadherin and beta-catenin are adhesion molecules that promote
      integrity and stability of the urothelium. A decrease in their expression is
      associated with more aggressive tumour phenotypes with the ability to invade and
      metastasize. MATERIAL AND METHODS: 45 ICR male mice were used, of which 25
      received N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05%) in drinking water for a
      period of 12 weeks. Immunohistochemical expression was evaluated in all urinary
      bladder preparations for E-cadherin and for beta-catenin. RESULTS: Preneoplastic
      lesions showed staining patterns similar to normal urothelium. In simple and
      nodular hyperplasia, membrane staining was dominant (66.7-78.6 and 50-100%,
      respectively). In dysplasia a cytoplasmic pattern was prevalent (86.7-100%).
      Neoplastic lesions exhibit an abnormal staining pattern (100%) with heterogeneous
      staining (cytoplasmic, nuclear and membrane staining). A strong correlation was
      observed between both adhesion molecule staining patterns (r = 0.83; p = 0.039).
      CONCLUSIONS: In mice, as in humans, E-cadherin and beta-catenin are valuable
      tools to investigate cellular adhesion status of urothelium and can be considered
      as indicators of tumour aggressiveness and evolution.

PMID- 23548312
TI  - Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and
      glioma stem cells and inhibit their cell migration and self-renewal.
AB  - MicroRNAs (miRNAs) have emerged as potential cancer therapeutics; however, their
      clinical use is hindered by lack of effective delivery mechanisms to tumor sites.
      Mesenchymal stem cells (MSCs) have been shown to migrate to experimental glioma
      and to exert anti-tumor effects by delivering cytotoxic compounds. Here, we
      examined the ability of MSCs derived from bone marrow, adipose tissue, placenta
      and umbilical cord to deliver synthetic miRNA mimics to glioma cells and glioma
      stem cells (GSCs). We examined the delivery of miR-124 and miR-145 mimics as
      glioma cells and GSCs express very low levels of these miRNAs. Using
      fluorescently labeled miRNA mimics and in situ hybridization, we demonstrated
      that all the MSCs examined delivered miR-124 and miR-145 mimics to co-cultured
      glioma cells and GSCs via gap junction- dependent and independent processes. The
      delivered miR-124 and miR-145 mimics significantly decreased the luciferase
      activity of their respected reporter target genes, SCP-1 and Sox2, and decreased
      the migration of glioma cells and the self-renewal of GSCs. Moreover, MSCs
      delivered Cy3-miR-124 mimic to glioma xenografts when administered
      intracranially. These results suggest that MSCs can deliver synthetic exogenous
      miRNA mimics to glioma cells and GSCs and may provide an efficient route of
      therapeutic miRNA delivery in vivo.

PMID- 23548315
TI  - Intracorneal blood removal six weeks after canaloplasty.
AB  - In a 71-year-old patient with bilateral open-angle glaucoma, intracorneal blood
      was found after a canaloplasty procedure in the right eye. Six weeks after
      surgery on ultrasound biomicroscopy examination, liquified blood and blood clots
      could be observed nasally in the deep corneal stroma close to the Descemet's
      membrane. The intracorneal blood was washed out with balanced saline solution
      following deep corneal incision and lamellar dissection. Descemet's membrane was
      reattached with air injection into the anterior chamber. Two months later, visual
      acuity improved to 20/50, intraocular pressure was 16 mm Hg without medication
      and confocal microscopy showed deep stromal folds and limited endothelial cell
      loss. Viscoelastic entering the cornea at Schwalbe's line and reflux of blood
      from the collector channels to Schlemm's canal can account for corneal hematoma.
      Even six weeks after canaloplasty, successful blood removal could be fulfilled
      without rupturing the Descemet's membrane.

PMID- 23548316
TI  - Distant metastatic retinoblastoma without central nervous system involvement.
AB  - Retinoblastoma is the most common intraocular malignancy in children, with a
      reported incidence ranging from 1 in 15,000 to 1 in 18,000 live births.
      Metastatic retinoblastoma is rare in developed countries, with a reported range
      from 4.8% in the United States to 5.8% in the United Kingdom. However, the
      frequency reported from developing countries varies from 9 to 11% at
      presentation. The mortality is very high owing to late presentations, delayed
      diagnosis compounded by socio-economic factors. The management of metastatic
      retinoblastoma is evolving, but it is still a challenge in pediatric oncology. We
      present a case of an extensive skeletal metastasis that initially presented as a
      massive orbital retinoblastoma. 

PMID- 23548317
TI  - Localized bi-nasal macular edema in optic chiasmal syndrome.
AB  - A 28-year-old healthy male complaining of vision loss in his right eye was
      discovered to have localized bi-nasal macular edema in the presence of a
      pituitary adenoma. The presence of a junctional scotoma composed by a central
      scotoma in the right eye associated with superior temporal quadrantanopia in the
      fellow eye was seen. The pattern detected in the visual field suggested the
      presence of an expansive mass at the level of the optic chiasm. Optical coherence
      tomography findings also revealed subtle macular thickness beyond normal in the
      superior and nasal quadrants of both maculae. This report illustrates the
      importance of suspecting a pituitary adenoma in the light of uncharacteristic
      retinal alterations. 

PMID- 23548318
TI  - Is there a correlation between structural alterations and retinal sensitivity in
      morphological patterns of diabetic macular edema?
AB  - Spectral domain optical coherence tomography (SDOCT) enables enhanced
      visualization of retinal layers and delineation of structural alterations in
      diabetic macular edema (DME). Microperimetry (MP) is a new technique that allows
      fundus-related testing of local retinal sensitivity. Combination of these two
      techniques would enable a structure-function correlation with insights into
      pathomechanism of vision loss in DME. To correlate retinal structural derangement
      with retinal sensitivity alterations in cases with diabetic macular edema, using
      SDOCT and MP. Prospective study of 34 eyes of 30 patients with DME. All patients
      underwent comprehensive ophthalmic examination, fluorescein angiography,
      microperimetry and SDOCT. Four distinct morphological patterns of DME were
      identified- diffuse retinal thickening (DRT), cystoid macular edema (CME),
      schitic retinal thickening (SRT) and neurosensory detachment (NSD) of fovea. Some
      retinal loci presented with a mixture of above patterns There was significant
      difference in retinal thickness between groups (P<0.001). Focal retinal
      sensitivity measurement revealed relatively preserved retinal sensitivity in
      areas with DRT (13.8 dB), moderately reduced sensitivity (7.9 dB) in areas with
      CME, and gross retinal sensitivity loss in areas with SRT (1.2 dB) and NSD (4.7
      dB) (P<0.001). Analysis of regional scotoma depth demonstrated similar pattern.
      Retinal sensitivity showed better correlation to OCT pattern (r=-0.68, P<0.001)
      than retinal thickness (r=-0.44, P<0.001). Structure-function correlation allows
      better understanding of the pathophysiology of visual loss in different
      morphological types of DME. Classification of macular edema into these categories
      has implications on the prognosis and predictive value of treatment.

PMID- 23548319
TI  - Ocular ischemic syndrome: a classical presentation of an uncommon condition.
AB  - We report a 47-year-old male who presented with acute mono-ocular vision loss,
      and had classical signs of global ocular ischemia in the right eye. Fundus
      fluorescein angiography demonstrated delayed choroidal filling and no perfusion
      of retinal vasculature. Carotid Doppler and computed tomogram (CT) angiography
      studies revealed extensive bilateral atherosclerotic disease involving the
      carotid circulation. Ophthalmologists must be aware of the possibility of this
      potentially fatal condition, which is extremely rare. An astute clinical
      diagnosis, targeted workup for systemic associations and a prompt referral may
      turn out to be life-saving. 

PMID- 23548320
TI  - Hypertensive iridocyclitis associated with delayed onset biopsy proven
      Cytomegalovirus retinitis.
AB  - We describe a case of primary hypertensive iridocyclitis with biopsy-proven
      Cytomegaloviral retinitis. It is an observational case report of a 69-year-old
      diabetic gentleman on azathioprine for Crohn's disease who presented with
      recurrent episodes of hypertensive iridocyclitis. On the 4 th attendance in 5
      months, a granular white lesion was noted in the temporal periphery of the mid
      peripheral fundus and a chorioretinal and vitreous biopsy performed. Vitreous PCR
      was positive for Cytomegalovirus (CMV). Hematoxylin and eosin staining revealed
      cytomegalic-like inclusions within necrotic neural retina. Transmission electron
      microscopy revealed herpes family virus particles and immunohistochemistry
      demonstrated CMV protein. This case provides further evidence implicating CMV
      infection in the etiology of hypertensive iridocyclitis. With hindsight, the
      cumulative effect of diabetes and azathioprine on the immune surveillance system
      proved sufficient to render the patient susceptible to CMV retinitis. 

PMID- 23548323
TI  - Uterine transplantation: towards clinical application.

PMID- 23548324
TI  - One-year surveillance of ESKAPE pathogens in an intensive care unit of Monterrey,
      Mexico.
AB  - BACKGROUND: Bacterial species from the ESKAPE group (i.e. Enterococcus faecium,
      Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii,
      Pseudomonas aeruginosa and Enterobacter species) are frequently resistant to
      antibiotics. The purpose of this study was to monitor the incidence of ESKAPE
      pathogens at the intensive care unit (ICU) of a tertiary care hospital in
      Monterrey, Mexico. METHODS: All clinically relevant organisms isolated from June
      2011 to June 2012 were included. Identification and susceptibility testing was
      performed using panels from Sensititre. Resistance to oxacillin, for S. aureus,
      and the production of extended spectrum beta-lactamases (ESBLs), for K.
      pneumonia, were determined as defined by the Clinical Laboratory Standards
      Institute. Also, the presence of vanA and vanB genes was determined in E. faecium
      vancomycin (VAN)-resistant isolates. RESULTS: The majority of pathogens (64.5%)
      isolated in the ICU unit were from the ESKAPE group. The organisms most
      frequently isolated were A. baumannii (15.8%) and P. aeruginosa (14.3%). A high
      resistance to carbapenems was detected for A. baumannii (75.3%) while 62% of S.
      aureus isolates were confirmed to be methicillin resistant. Of the K. pneumoniae
      isolates, 36.9% were ESBL producers. We detected three E. faecium VAN-resistant
      isolates, all of which contained the vanA gene. CONCLUSION: The presence of the
      ESKAPE group of pathogens is a major problem in the ICU setting. The results of
      this study support the implementation of special antimicrobial strategies to
      specifically target these microorganisms.

PMID- 23548325
TI  - Synergistic analgesic effects between neuronostatin and morphine at the
      supraspinal level.
AB  - Neuronostatin, a 13-amino acid peptide, is encoded in the somatostatin pro
      hormone. I.c.v. administration of neuronostatin produces a significant
      antinociceptive effect in the mouse tail-flick test, which is mediated by
      endogenous opioid receptor. However, the direct functional interaction between
      morphine and neuronostatin has not been characterized. In the present study,
      effect of neuronostatin on morphine analgesia was investigated in the tail-flick
      test. Our findings showed that i.c.v. administration of neuronostatin
      (0.3nmol/mouse i.c.v.) significantly enhanced the antinociceptive effect of
      morphine (2.5, 5 or 10MUg/kg) at the supraspinal level. Results of antagonism
      experiments suggested that the synergistic analgesia induced by morphine and
      neuronostatin was mediated by MU- and k-opioid receptors not delta-opioid
      receptor. In conclusion, there may be a cascade amplification phenomenon when
      morphine and neuronostatin were co-administered in acute pain model. The above
      results provide evidence for the potential use of neuronostatin in combination
      with morphine to control pain and addiction.

PMID- 23548327
TI  - Comparing two Bayes methods based on the free energy functions in Bernoulli
      mixtures.
AB  - Hierarchical learning models are ubiquitously employed in information science and
      data engineering. The structure makes the posterior distribution complicated in
      the Bayes method. Then, the prediction including construction of the posterior is
      not tractable though advantages of the method are empirically well known. The
      variational Bayes method is widely used as an approximation method for
      application; it has the tractable posterior on the basis of the variational free
      energy function. The asymptotic behavior has been studied in many hierarchical
      models and a phase transition is observed. The exact form of the asymptotic
      variational Bayes energy is derived in Bernoulli mixture models and the phase
      diagram shows that there are three types of parameter learning. However, the
      approximation accuracy or interpretation of the transition point has not been
      clarified yet. The present paper precisely analyzes the Bayes free energy
      function of the Bernoulli mixtures. Comparing free energy functions in these two
      Bayes methods, we can determine the approximation accuracy and elucidate behavior
      of the parameter learning. Our results claim that the Bayes free energy has the
      same learning types while the transition points are different.

PMID- 23548328
TI  - Is there a role for N-terminal probrain-type natriuretic peptide in determining
      volume status in haemodialysis patients?
AB  - BACKGROUND/AIMS: Natriuretic peptides have been reported to be a valuable
      biomarker for predicting cardiac events and mortality for haemodialysis patients.
      However, there has been a debate as to whether these biomarkers can be used to
      assess volume overload and help determine dry weight. METHODS: We measured the N
      terminal probrain natriuretic peptide (NTproBNP) in 366 stable haemodialysis
      outpatients with a corresponding pre- and post-dialysis multifrequency
      bioimpedance assessment of extracellular water (ECW)/total body water (TBW).
      RESULTS: Median age was 61 years (46-73); 58.5% were male, 28.5% diabetic, and
      37.7% Caucasoid; 71.1% had a history of hypertension, 8.4% of myocardial
      infarction, and 9.3% of coronary artery bypass surgery; dialysis vintage was 54
      months (22-85.5), and urea reduction ratio was 73.4 +/- 7.6%. Median post
      dialysis NTproBNP was 179 pmol/l (68-535), pre-dialysis ECW/TBW was 0.393 +/-
      0.014, and post-dialysis ECW/TBW was 0.385 +/- 0.015. On multivariate analysis
      log NTproBNP was associated with post-dialysis ECW/TBW (beta 9.09, 95% CI 3.22
      14.95, p = 0.003), mean arterial pressure (beta 0.0087, 95% CI -0.0045 to -0.013,
      p = 0.000), and ultrafiltration rate (ml/kg . h; beta 0.038, 95% CI 0.01-0.06, p
      = 0.001). CONCLUSION: In this study postdialysis NTproBNP values were correlated
      with direct assessments of volume status in haemodialysis patients, i.e. by
      ECW/TBW, or indirect measures of volume overload, i.e. ultrafiltration rate and
      post-dialysis mean arterial blood pressure. This suggests that serial NTproBNP
      values may aid clinical assessments of volume status in dialysis patients.

PMID- 23548329
TI  - Hierarchical random cellular neural networks for system-level brain-like signal
      processing.
AB  - Sensory information processing and cognition in brains are modeled using dynamic
      systems theory. The brain's dynamic state is described by a trajectory evolving
      in a high-dimensional state space. We introduce a hierarchy of random cellular
      automata as the mathematical tools to describe the spatio-temporal dynamics of
      the cortex. The corresponding brain model is called neuropercolation which has
      distinct advantages compared to traditional models using differential equations,
      especially in describing spatio-temporal discontinuities in the form of phase
      transitions. Phase transitions demarcate singularities in brain operations at
      critical conditions, which are viewed as hallmarks of higher cognition and
      awareness experience. The introduced Monte-Carlo simulations obtained by parallel
      computing point to the importance of computer implementations using very large
      scale integration (VLSI) and analog platforms. 

PMID- 23548330
TI  - Low frequency transcranial magnetic stimulation downregulates expression of
      stress genes in blood leucocytes: preliminary evidence.

PMID- 23548332
TI  - What can we learn from a decade of promoting safe embryo transfer practices? A
      comparative analysis of policies and outcomes in the UK and Australia, 2001-2010.
AB  - STUDY QUESTION: Given similar socio-demographic profiles and costs of healthcare,
      why has Australia been significantly more successful than the UK in reducing the
      assisted reproductive technology (ART) multiple birth rate? SUMMARY ANSWER: The
      Australian model of supportive public ART funding, permissive clinical guidelines
      and an absence of published clinic league tables has enabled Australian fertility
      specialists to act collectively to achieve rapid and widespread adoption of
      single embryo transfer (SET). WHAT IS KNOWN ALREADY: There are striking
      differences in ART utilization and clinical practice between Australia and the
      UK. The ART multiple birth rate in Australia is <8% compared with slightly <20%
      in the UK. The role played by public funding, clinical guidelines, league tables
      and educational campaigns deserves further evaluation. STUDY DESIGN, SIZE,
      DURATION: Parallel time-series analysis was performed on ART treatment and
      outcome data sourced from the Human Fertilisation and Embryology Authority (HFEA)
      ART Registry and the Australian and New Zealand Assisted Reproduction Database
      (ANZARD). Funding arrangements, clinical practice guidelines and key professional
      and public education campaigns were mapped to trends in clinical practice and ART
      treatment outcomes between 2001 and 2010. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: A total of 425 360 and 422 003 autologous treatment cycles undertaken
      between 2001 and 2010 in the UK and Australia were analysed. MAIN RESULTS AND THE
      ROLE OF CHANCE: From 2001 to 2010, the most striking difference in clinical
      practice was the increase in SET cycles in Australia from 21 to 70% of cycles,
      compared with an increase from 8.4 to 31% in the UK. In 2004-2005, both countries
      introduced clinical guidelines encouraging safe embryo practices, however,
      Australia has a history of supportive funding for ART, while the National Health
      Service has a more restrictive and fragmented approach. While clinical guidelines
      and education campaigns have an important role to play, funding remains a key
      element in the promotion of SET. LIMITATIONS, REASONS FOR CAUTION: This is a
      descriptive population study and therefore quantifying the independent effect of
      differential levels of public funding was not possible. WIDER IMPLICATIONS OF THE
      FINDINGS: With demand for ART continuing to increase worldwide, it is imperative
      that we remove barriers that impede safe embryo transfer practices. This analysis
      highlights the importance of supportive public funding in achieving this goal.

PMID- 23548331
TI  - Ketamine regulates the presynaptic release machinery in the hippocampus.
AB  - In the search for new drug targets, that may help point the way to develop fast
      acting treatments for mood disorders, we have explored molecular pathways
      regulated by ketamine, an NMDA receptor antagonist, which has consistently shown
      antidepressant response within a few hours of administration. Using Sprague
      Dawley rats we investigated the effects of ketamine on the presynaptic release
      machinery responsible for neurotransmitter release at 1, 2 and 4 h as well as 7
      days after administration of a single subanesthetic dose of ketamine (15 mg/kg).
      A large reduction in the accumulation of SNARE complexes was observed in
      hippocampal synaptic membranes after 1, 2 and 4 h of ketamine administration. In
      parallel, we found a selective reduction in the expression of the synaptic
      vesicle protein synaptotagmin I and an increase in the levels of synapsin I in
      hippocampal synaptosomes suggesting a mechanism by which ketamine reduces SNARE
      complex formation, in part, by regulating the number of synaptic vesicles in the
      nerve terminals. Moreover, ketamine reduced Thr(286)-phosphorylated alphaCaMKII
      and its interaction with syntaxin 1A, which identifies CaMKII as a potential
      target for second messenger-mediated actions of ketamine. In addition, despite
      previous reports of ketamine-induced inhibition of GSK-3, we were unable to
      detect regulation of its activity after ketamine administration. Our findings
      demonstrate that ketamine rapidly induces changes in the hippocampal presynaptic
      machinery similar to those that are obtained only with chronic treatments with
      traditional antidepressants. This suggests that reduction of neurotransmitter
      release in the hippocampus has possible relevance for the rapid antidepressant
      effect of ketamine.

PMID- 23548333
TI  - A review of thrombosis and antithrombotic therapy in microvascular surgery.
AB  - Despite a remarkable expansion of microsurgery, there is still no international
      consensus about routinely used prophylactic antithrombotic agents. Most treatment
      regimens still use aspirin, heparin (low-molecular-weight and unfractionated
      heparin) or colloids (hydroxyphenylacetate 6%/dextran); however, clear evidence
      for the clinical benefit of an ideal administration regimen or one agent over the
      other has not yet been established. Instead of searching for the one regime that
      fits all, an increasing number of reviews from different disciplines describe
      multistep approaches that optimize what has been shown to be most promising. This
      includes the use of antithrombotic agents, proper risk assessment, secondary
      prevention and professional training to optimize microsurgical skills. In this
      review, we describe factors included in traditional approaches and also emphasize
      the value of good surgical technique, which while recognized by all to be one of
      the most important factors for success, receives less emphasis in reviews
      describing thrombosis prophylaxis in microvascular surgery.

PMID- 23548334
TI  - Loeffler's endocarditis presenting with acute abdominal aortic obstruction.
AB  - Loeffler's endocarditis is a complication of diseases associated with the
      idiopathic hypereosinophilic syndrome, which is characterised by persistently
      elevated blood eosinophil counts with symptoms and signs of organ involvement
      especially in the heart, vascular system, nervous system and bone marrow. We
      report the involvements of the endocardium and aorta, without endomyocardial
      fibrosis and the complete resolution of the endocardial eosinophilic infiltration
      with steroids and anticoagulation therapy.

PMID- 23548335
TI  - New generation coronary stent technology--is the future biodegradable?
AB  - A new generation of drug eluting coronary stents are undergoing clinical trial
      evaluation and being introduced into clinical practice. These technologies
      comprise a broad range of innovations and include non-polymeric stents,
      biodegradable polymer coated stents and fully biodegradable scaffolds. The new
      devices are designed to improve long-term safety and efficacy and overcome
      limitations associated with a durable polymer and a persistent metallic stent
      scaffold. At the present time, none have demonstrated convincing superiority over
      current second generation drug eluting stents and large, long-term randomised
      controlled trials are required. 

PMID- 23548336
TI  - Retrograde cardioplegia revisited: open technique for long aortic cross clamping.
AB  - BACKGROUND: The efficacy of retrograde cardioplegia for myocardial protection is
      still controversial. In our institution, we exclusively use intermittent
      administration of tepid, undiluted blood supplemented with potassium and
      magnesium for the cases with aortic insufficiency, requiring aortotomy, or
      undergoing mitral valve repair. In using this retrograde technique, we make a
      point of cannulating a retrograde perfusion catheter under direct vision
      following right atriotomy. The purpose of this retrospective study is to evaluate
      the clinical outcome of using this technique. METHODS: This study comprises 49
      patients who underwent elective valve surgery using direct-vision retrograde
      cardioplegia exclusively, requiring more than 3h aortic cross-clamping. Their
      clinical outcome was reviewed retrospectively. RESULTS: There was no hospital
      mortality in this study. No patient was noted to have evidence of mediastinitis,
      myocardial infarction, or cerebral complications in the postoperative period. The
      case requiring the longest aortic cross-clamping time (380 min) survived the
      operation without the use of intra-aortic balloon pumping or percutaneous
      cardiopulmonary support, and the postoperative course was uneventful.
      CONCLUSIONS: Our result suggests that direct-vision retrograde cardioplegia is a
      safe and effective method of cardioplegia delivery, and provides a longer period
      of myocardial protection than previously thought.

PMID- 23548337
TI  - Surgery of myasthenia gravis associated or not with thymoma: a retrospective
      study of 43 cases.
AB  - OBJECTIVES: Thymectomy is a surgical treatment of myasthenia gravis. Our goal is
      to report our experience in the surgical treatment of myasthenia gravis with or
      without thymoma and a review of the literature. MATERIALS AND METHODS: This is a
      retrospective study over a period of 10 years (2001-2010) on 43 patients: 28
      women and 15 men with a mean age of 39.3 years (range 16-68 years). The
      myasthenia gravis was confirmed by clinical, electromyographic data and the
      presence of antibodies to acetylcholine receptors. RESULTS: Computed tomography
      objectified thymic mass in 14 cases (32.5%) enlarged thymus without visible mass
      in eight cases (18.6%). All patients received anticholinesterase, cortico
      steroids in 25 cases and in three cases plasmapheresis was required. The surgical
      approach was total sternotomy (n=32 cases), cervicotomy (n=2), cervical and
      manubriotomy (n=1), a manubriotomy (n=3) and a thoracotomy in five cases
      (lateralised thymoma). All patients underwent a total thymectomy associated or
      not with resection of the tumour. Intensive Care Unit was necessary for at least
      24h up to six days. The postoperative course was marked by a myasthaenic crisis
      (n=2) and respiratory failure (n=3) with a favourable outcome. The prognosis was
      marked by a complete remission in 14 cases, partial remission in 11 patients,
      stabilisation (n=16 cases) and increasing crisis in two patients. CONCLUSION:
      Thymectomy certainly allows clinical improvement and reduced crisis of myasthenia
      gravis. Long term monitoring will confirm the benefit of non-oncological
      thymectomy alone or in combination with standard treatments for patients with
      generalised myasthenia gravis without thymoma.

PMID- 23548338
TI  - Myocardial revascularisation in renal dysfunction: a systematic review and meta
      analysis.
AB  - BACKGROUND: Coronary artery disease is highly prevalent in patients with end
      stage renal disease. Yet randomised controlled trials are lacking, and decisions
      are based on retrospective cohort studies which present conflicting outcomes.
      Hence we conducted a systematic review and meta-analysis comparing outcomes in
      patients with end-stage renal disease and renal dysfunction undergoing
      percutaneous intervention (PCI) and coronary artery bypass grafting (CABG), with
      a particular focus on contemporary studies implementing drug-eluting stents.
      METHODS: MEDLINE, EMBASE, World of Science, and the Cochrane library were
      searched for randomised controlled (RCT) and observational studies comparing
      clinical outcomes such as early mortality, myocardial infarction, need for repeat
      revascularisation and angina in patients undergoing PCI or CABG. We used random
      effect models to compare risk ratios (RR) within groups. RESULTS: One RCT and 15
      observational studies (7588 PCI and 9206 CABG patients) met inclusion criteria.
      Early mortality favoured the PCI cohort (4.2% vs 8.5%) [risk ratio=0.51(0.40,
      0.64), p<0.01]. The need for repeat revascularisation was significantly lower in
      the CABG cohort (7.3% vs 17.8%; p<0.01). Pooled analysis of studies implementing
      a drug eluting stent still favoured CABG with regards to repeat revascularisation
      (5% vs 14%; p<0.01) and MACE (15% vs 27%; p=0.03), while early mortality was less
      in the DES-PCI cohort (2.4% vs 5.1%; p=0.04). CONCLUSION: Compared to
      percutaneous intervention, coronary artery bypass grafting is associated with
      higher early/30-day mortality in patients with renal dysfunction or end-stage
      renal disease. The need for repeat revascularisation is significantly higher with
      percutaneous intervention, even with the use of a drug-eluting stent.

PMID- 23548339
TI  - The source and significance of DNA damage in human spermatozoa; a commentary on
      diagnostic strategies and straw man fallacies.
AB  - This article considers the origins of DNA damage in human spermatozoa, the
      methods that are available to monitor this aspect of semen quality and the
      clinical significance of such measurements. DNA damage in spermatozoa appears to
      be largely oxidative in nature, inversely correlated with levels of nuclear
      protamination and frequently associated with the activation of a truncated
      apoptotic pathway. DNA base adducts formed as a result of oxidative attack are
      released from the spermatozoa into the extracellular space through the action of
      a glycosylase, OGG1. This creates an abasic site, which is not resolved until
      fertilization because spermatozoa do not possess the molecular machinery needed
      to continue the base excision repair pathway. The abasic sites so generated in
      human spermatozoa are readily detected by SCSA or the Comet assay; however, no
      signal is detectable with TUNEL. This is because spermatozoa lack the enzyme
      (APE1) needed to create the free 3' hydroxyl groups required by this detection
      system. Nevertheless, spermatozoa do eventually become TUNEL positive as they
      enter the perimortem. The American Society of Reproductive Medicine Practice
      Committee has suggested that DNA damage in spermatozoa should not be assessed
      because the correlation with pregnancy is inconsistent across independent
      studies. However, this is a straw man argument. The reason why such assays should
      be undertaken is not just that they reflect the underlying quality of
      spermatogenesis but, more importantly, that the DNA damage they reveal may have
      detrimental effects on the developmental normality of the embryo and the health
      of possible future children. 

PMID- 23548340
TI  - Association between loss-of-function mutations in the filaggrin gene and self
      reported food allergy and alcohol sensitivity.
AB  - BACKGROUND: Loss-of-function mutations of the filaggrin (FLG) gene cause an
      impaired skin barrier and increase the risk of atopic dermatitis. Interestingly,
      FLG mutations have also been found to be associated with a high risk of peanut
      allergy. OBJECTIVE: We investigated the association of FLG mutations with self
      reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol
      sensitivity. METHODS: A total of 3,471 adults from the general population
      participated in a health examination. Information on food allergies, OAS and
      alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were
      defined as having at least one null mutation allele of R501X or 2282del4. Primary
      lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235
      polymorphism. RESULTS: FLG mutations were associated with a higher risk of self
      reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI
      1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI
      1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum
      specific IgE was measured in a subsample and confirmed the association between
      FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI
      was observed in relation to self-reported allergy to milk. Furthermore, FLG
      mutations were associated with a higher risk of alcohol sensitivity. CONCLUSIONS:
      We found that loss-of-function mutations in the FLG gene were significantly
      associated with self-reported food allergy and alcohol sensitivity, but not with
      OAS. These findings, if confirmed, support the idea that skin barrier functions
      may be involved in the pathogenesis of food allergy.

PMID- 23548341
TI  - The timing of exposure in clinic-based treatment for childhood anxiety disorders.
AB  - The present study examines treatment length and timing of exposure from two child
      anxiety disorders clinics. Data regarding symptoms and treatment characteristics
      for 28 youth were prospectively obtained through self, parent, and therapist
      report at each session. Information regarding length of treatment, timing of
      exposure initiation, and drop-out rates were compared with those obtained through
      efficacy and effectiveness trials of manualized treatment for anxious youth.
      Findings from the authors' clinical data revealed significantly shorter treatment
      duration with exposures implemented sooner than in the previous studies. Dropout
      rates were significantly higher than in the efficacy trial but comparable with
      the effectiveness trial. Outcome data from a subset of eight patients revealed
      large effect sizes. These findings suggest that effective treatment can be
      shorter and more focused on exposure than is often outlined in manuals and have
      important implications for outcome research and dissemination.

PMID- 23548342
TI  - Patients' preferences regarding choice of end-stage renal disease treatment
      options.
AB  - BACKGROUND: Dialysis registries have reported a low take-up of home treatment.
      The aim of our study was to report patients' preferred treatment options for end
      stage renal disease (ESRD) after information delivery, patients' characteristics
      by treatment preference, and the reasons for differences between treatment
      preference and the treatment delivered. METHODS: A prospective cohort study on
      patients seen in our nephrology department between January 2009 and June 2011
      included all patients with chronic kidney disease (GFR <20 ml/min/1.73 m(2)) and
      incident dialysis patients who received an information program about ESRD
      treatment options. RESULTS: 228 patients received information delivery and either
      expressed a preference for a given renal replacement therapy (peritoneal
      dialysis, PD: 42%; hemodialysis, HD: 33%), remained undecided (20%) or expressed
      reluctance to undergo renal replacement therapy (5%). Multivariate analysis
      revealed that compared to HD preference, patients preferring PD were older (OR
      1.02, 95% CI 1.0-1.04), had a lower BMI (OR 0.9, 95% CI 0.87-0.98) and were more
      likely to have been informed before rather than after starting dialysis (OR 3.4,
      95% CI 1.5-7.4); home treatment was the main reason given for preferring PD.
      Undecided patients were mainly women and the majority were eventually treated by
      HD. Reluctant patients were the oldest (OR 1.12, 95% CI 1.02-1.22) and were
      rarely treated by dialysis. Only 24% of patients informed before and 8% of
      patients informed after starting dialysis were ultimately treated with PD.
      Reasons for a mismatch between dialysis modality preference and treatment
      delivered were equally distributed between medical and nonmedical. CONCLUSION:
      Patients should be systematically informed before starting dialysis, patients'
      preferences should be taken into account before organizing dialysis and all
      treatment modalities should be available in all centers.

PMID- 23548343
TI  - Null association between tamoxifen use and dementia in Danish breast cancer
      patients.
AB  - BACKGROUND: Concerns have been raised about the risk of dementia associated with
      antiestrogen adjuvant therapy in breast cancer, but study results have been
      inconsistent. We examined whether tamoxifen or other endocrine therapy was
      associated with dementia risk in a large population of patients with breast
      cancer. METHODS: We used Danish nationwide medical registries to identify
      patients with breast cancer diagnosed between 1990 and 2004, use of endocrine
      therapy, and subsequent diagnoses of dementia. We used Cox regression to estimate
      the risk of dementia among patients who received five years of tamoxifen or other
      endocrine therapies. RESULTS: The study included 16,419 patients with breast
      cancer. In this cohort, 37% were unexposed to endocrine therapy, 9% had five
      years of tamoxifen therapy, and 54% had other endocrine regimens, some of them
      containing tamoxifen for less than five years with subsequent aromatase inhibitor
      therapy. Tamoxifen therapy was associated with a near-null risk of dementia [HR,
      1.4; 95% confidence interval (CI), 1.0-1.9], and a null association was observed
      after death was taken into account as a competing risk (sub-HR, 1.0; 95% CI, 0.76
      1.4). CONCLUSIONS: No clinically relevant association between use of tamoxifen or
      other endocrine therapy and risk of dementia was observed. IMPACT: Our result
      contradicts earlier research findings suggesting tamoxifen and other endocrine
      therapies increase the risk of dementia in breast cancer patients.

PMID- 23548344
TI  - [Significance of echocardiography in acute coronary syndrome].
AB  - The paper contains description of possibilities and limitations of ultrasound
      diagnosis in patients with acute coronary syndrome (ACS). Main attention is paid
      to possibilities of echocardiographic diagnosis of myocardial infarction (MI) and
      its complications, as well as to differential diagnostics of ACS and nonischemic
      conditions causing chest pain and infarction-like ECG changes. Data are presented
      demonstrating substantial lowering of rates of some complications of MI in
      patients subjected to thrombolytic therapy or interventional procedures of
      myocardial revascularization.

PMID- 23548345
TI  - [Adherence to guidelines on management of acute coronary syndrome in Russian
      hospitals and outcomes of hospitalization (data from the RECORD-2 Registry)].
AB  - BACKGROUND: Complete following existing guidelines for management of acute
      coronary syndrome (ACS) is known to be associated with better outcomes. Partly
      this is explained by lesser adherence to recommendations in high risk patients.
      Aim of our study was to assess relationship between degree of following current
      guidelines and in hospital outcomes independently from initial assessment of
      risk. METHODS: Each key recommendation from guidelines issued between 2008 and
      2011 (13 for STE ACS, 12 for NSTE ACS) was given weight of 1. Sum of these units
      constituted index of guideline adherence (IGA). IGA was retrospectively
      calculated for 1656 patients included in Russian independent ACS registry RECORD
      2 (7 hospitals, duration 04.2009 to 04.2011). The patients were divided into 2
      groups according to quartiles of IGA distribution: 1) low adherence group
      (quartiles I-II); 2) high adherence group (quartiles III-IV). RESULTS: In low
      adherence compared with high adherence group there were significantly more
      patients more or equal 65 years (=0.0007), with chronic heart failure [CHF]
      (<0.0001), previous stroke (<0.0001), atrial fibrillation [AF] (=0.0002), Killip
      class more or equal II (=0.0065), high risk of death by GRACE score (=0.035).
      Inhospital mortality was 9.3 and 2.4% in low and high adherence group,
      respectively (p<0.0001). The following independent predictors of inhospital death
      were identified: IGA quartiles I-II (odds ratio [OR] 4.0; 95% confidence interval
      [CI] 2.3-7.1; <0.0001), high GRACE score (OR 3.3; 95% CI 1.8-6.0; <0.0001),
      admission systolic BP less or equal 100 mm Hg (OR 3.1; 95% CI 1.8-5.4; <0.0001),
      admission serum glucose more or equal 8 mmol/l (OR 2.9; 95% CI 1.8-4.7; <0.0001),
      age more or equal 65 years (OR 2.3; 95% CI 1.3-4.0; =0.005), ST elevation more or
      equal 1 mm on first ECG (OR 1.7; 95% CI 1.1-2.5; =0.013). From groups with low
      and high adherence to guidelines we selected pairs of patients (n=588) with
      similar (or close) age, type of ACS, GRACE score, Killip class, presence of other
      important risk factors (CHF, AF, previous stroke), and formed 2 equal subgroups
      without significant differences in important demographic, anamnestic, clinical
      and laboratory data. Hospital mortality was 7.8 and 2.7% in low and high
      adherence subgroup, respectively (p<0.0001). CONCLUSIONS: In RECORD-2 ACS
      registry low adherence to guidelines was more frequent among high risk patients
      and was independent predictor of inhospital death. Association between degree of
      guidelines adherence and outcomes persisted after equalizing groups by some
      factors of risk of mortality.

PMID- 23548347
TI  - [Factors associated with mitral regurgitation in patients with coronary artery
      disease in the absence of myocardial infarction].
AB  - It is known that not only postinfarction left ventricular (LV) remodeling but
      also chronic regional myocardial hypoperfusion may cause a compensatory
      hypertrophy of undamaged areas of the left ventricle. Can chronic LV
      hypoperfusion lead to the development of mitral regurgitation (MR) in CAD
      patients without previous myocardial infarction We selected patients with
      significant coronary stenosis (>75%) of at least one epicardial artery who had no
      acute or previous myocardial infarction: 1162 patients without MR and 76 patients
      with moderate and severe MR. Patients with MR more often had higher NYHA
      functional class (II-IV) (91.7 vs 63.0%, p =0.004) and arrhythmias (60.3 vs
      14.6%, p<0.001). They also had significantly higher echocardiographic indices of
      left atrial dimension (23.5+/-2.9 vs. 20.3+/-2.1 mm/m2). MR was independently
      associated with NYHA class of congestive heart failure, arrhythmias, and index of
      the left atrium size. No association between MR and the localization of
      significant coronary lesions was found.

PMID- 23548348
TI  - [Increment of family burdening by hereditary abnormalities of cardiac conduction
      (follow-up for 10 years)].

PMID- 23548346
TI  - [Effect of intracoronary and intravenous administration of tirofiban loading dose
      in patients underwent percutaneous coronary interventions because of acute
      coronary syndrome].
AB  - Aim of this multicenter retrospective study was assessment of effect of
      intracoronary administration of tirofiban loading dose in troponin positive
      patients with acute coronary syndrome (ACS). We analyzed multicenter data base of
      patients subjected to percutaneous coronary interventions (PCI) because of ST
      elevation or non-ST elevation ACS from October 2010 to October 2011. Patients who
      received loading doses of aspirin (300 mg) and clopidogrel (600 mg) before PCI
      and tirofiban (10 mg/kg bolus with subsequent infusion 0.15 mg/kg/min for 24 h)
      were selected for the study (n=133, 89 with intravenous and 44 - intracoronary
      administration of tirofiban loading dose). We assessed hospital mortality,
      myocardial reinfarctions (reMI), necessity of target vessel revascularization
      (TVR) and pronounced bleedings. There were no significant differences in
      mortality, reMI, and TVR between two groups. However major adverse cardiac events
      was significantly less in patients who received intracoronary tirofiban (6.8 vs.
      21.3% in i.v. group; p=0.046). Hospital stay was significantly shorter in
      intracoronary compared with i.v. group (3.84+/-0.96 vs. 4.55+/-1.11 days;
      p=0.001). Rates of bleedings did not differ significantly between groups. Thus
      compared with i.v. intracoronary administration of tirofiban loading dose allows
      lower rate of major adverse cardiac events as well as to shorten length of
      hospital stay of patients with ACS.

PMID- 23548349
TI  - [Reflected high-intensity motion signals as markers of left ventricular diastolic
      dysfunction].
AB  - Reflected high-intensity signals of left ventricular motion can be used for
      assessment of diastolic function of left ventricle. There are many correlations
      between reflected high-intensity signals, transmitral flow, and tissue Doppler
      imaging parameters. Diagnostic criteria of LV diastolic dysfunction based on
      measurement of LV motion are suggested.

PMID- 23548350
TI  - [24-hour heart rate profile in assessment of target organs in women with arterial
      hypertension].
AB  - AIM: To study relationships of 24-hour heart rate (HR) profile with involvement
      of the heart and kidney in women with arterial hypertension (AH). MATERIAL: We
      examined women (n=273) aged 40-70 years with essential 2-3 degree AH. METHODS:
      Blood pressure (BP) measurements (8 times in a week), electrocardiography,
      echocardiography, ambulatory BP monitoring, complex laboratory diagnostics.
      RESULTS: Less than 10% HR lowering was registered in 22.7% of patients. Compared
      with the group with normal HR profile this group was characterized by high levels
      of clinical systolic and diastolic BP (SBP, DBP), mean 24-hour BP, nocturnal BP,
      SBP time index, as well as low levels of 24-hour SBP, HR, and HR variability.
      Same group had also significantly greater left atrial dimensions, and higher
      values of NT-proBNP and total risk according to SCORE (Systematic Coronary Risk
      Estimation). Correlation analysis revealed significant reverse association
      between 24-hour HR index which reflected circadian character of cardiac rhythm,
      left atrial dimension (r=-0.212) and NT-proBNP (r=-0.346). Flat HR profile was
      not statistically significant for detection of cardiac pathology (odds ratio
      1.19; 95% confidence interval from 0.67 to 2.14). CONCLUSION: Insufficient
      nocturnal HR lowering in women with AH was not associated with significant
      changes of the myocardium and kidney and clear cat links with dyslipidemia,
      obesity, and smoking.

PMID- 23548351
TI  - [Epicardial adiposity as risk factor of coronary atherosclerosis].
AB  - AIM: To study effect of epicardial adiposity on risk of development and severity
      of coronary atherosclerosis. MATERIAL AND METHODS: We registered classical
      metabolic risk factors (RF) and additional factors of cardiovascular risk in 138
      men aged 55.47+/-9.07 years with ischemic heart disease (IHD), functional class
      (FC) II-III angina, and I-III degree obesity. Diagnostic coronary angiography
      (CAG) was performed in all patients. Thickness of epicardial fat (tEF) in
      millimeters was measured at transthoracic echocardiography (ECG). RESULTS:
      Average tEF indexes were highest (10 [8; 10] mm) in the group of patients with
      multiple stenoses in coronary arteries (CA). According to ROC-analysis tEF
      appeared to be a predictor of significant coronary atherosclerosis. Its
      sensitivity was 80.4%, specificity - 67.6 % (cut-off value 6 mm). Epicardial
      adiposity was among factors associated with presence of coronary atherosclerosis
      (odds ratio [OR] 4.44, 95% confidence interval [CI] 2,06 to 9.59; p<0,001) along
      with age (OR 6.56; 95% CI 2.59 to 16.60; p=0,001), leptin (OR 3.50; 95% CI 1.46
      to 8.37; p <0,001), resistin (OR 3.13; 95% CI 1.32 to 7.42; p <0,001) and waist
      circumference (OR 1.65; 95% CI 0.72 to 3.80; p=0.018).

PMID- 23548352
TI  - [Factors affecting results of coronary bypass surgery in elderly patients].
AB  - Study aim was to compare rates of perioperative complications of coronary bypass
      surgery in patients of various age groups and to analyze factors associated with
      their appearance. We retrospectively studied 2411 case histories of patients
      subjected to coronary artery bypass surgery between January 2006 and December
      2009. According to their age at surgery patients were divided in 4 groups: <60
      years (n=1555, mean age 53+/-6 years), 60-64 years (n=379, mean age 61+/-3
      years), 65-69 years (n=335, mean age 67+/-2 years), >70 years (n=142, mean age
      71+/-3 years). In older age groups hospital mortality and total number of
      complications were greater than in patients aged <60 years. Hospital mortality
      and rates of postoperative complications did not significantly differ between
      groups of patients aged 60-64, 65-69, and more or equal 70 years. Besides age the
      following factors were independently associated with hospital mortality:
      characteristics of extent of atherosclerosis (significant occlusive-stenotic
      lesions in arteries of lower extremities and extracranial arteries, history of
      stroke); lowering of left ventricular ejection fraction; and use of
      cardiopulmonary bypass.

PMID- 23548353
TI  - [Myocardial metabolism and metabolic drugs].
AB  - The article describes the basics of myocardial metabolism during normoxia and
      ischemia. It contains a brief description of the various drugs that affect the
      metabolic status of myocardium.

PMID- 23548354
TI  - [Radiofrequency sympathetic renal denervation: a new version of the old method of
      treatment resistant hypertension].

PMID- 23548355
TI  - [Fibric acid derivatives: focus on fenofibrate].

PMID- 23548356
TI  - [Arterial hypertension in diabetes mellitus: classical concepts and modern
      tendencies].
AB  - Some actual problems of arterial hypertension (AH) in metabolic disturbances and
      type 2 diabetes mellitus are considered in this review. Target arterial pressure
      levels and principles of correction of AH are specifically analyzed. Metaanalysis
      of large studies of efficacy of various groups of antihypertensive drugs in
      patients with AH and diabetes mellitus is presented. Special attention is given
      to results of multicenter clinical studies of effectiveness of carvediolol in
      patients with comorbid state.

PMID- 23548357
TI  - [Andersen-Tawil syndrome. Efficacy of class IC drugs].
AB  - A case of a rare disease - Andersen-Tawil the syndrome (ATS) is presented.
      Diagnosis of ATS, 7-th molecular-genetic variant of long QT syndrome was made
      basing on the characteristic clinical picture (periodic stress induced syncopal
      states), data of ECG and its Holter monitoring (pronounced QT prolongation, bouts
      of polymorphic bidirectional ventricular tachycardia), typical dysmorphic
      features (low-set ears, small mandible, brachydactyly, fifth-digit clinodactyly).
      However mutation of the KCNJ2 gene typical for this variant was not detected.
      Problems of pathogenesis, diagnostics, and treatment of the disease are discussed
      with special stress on class IC antiarrhythmic drugs.

PMID- 23548358
TI  - Efficacy and safety of desvenlafaxine treatment for hot flashes associated with
      menopause: a meta-analysis of randomized controlled trials.
AB  - Vasomotor symptoms, such as daytime hot flashes and nighttime awakenings due to
      hot flashes, are commonly associated with menopausal women. The aim of this study
      was to assess desvenlafaxine in moderate to severe hot flashes in postmenopausal
      women. Electronic databases were searched for relevant randomized controlled
      trials that compared desvenlafaxine to placebo for postmenopausal women affected
      with hot flashes. The main outcomes were mean differences (MD) or standardized
      mean differences (SMD) and 95% confidence interval (CI) for change of the hot
      flashes. Six randomized controlled trials were identified in the meta-analysis.
      Pooled change of moderate and severe hot flashes frequency reduced SMD of -0.49
      (95% CI -0.91 to -0.07) in desvenlafaxine 100 mg and -0.36 (95% CI -0.54 to 
      0.19) in desvenlafaxine 150 mg at week 12. Desvenlafaxine 100 mg reduced moderate
      and severe hot flashes frequency SMD of -0.74 (95% CI -1.05 to -0.44) within 26
      weeks. There is no evidence for an increased risk of cardiovascular,
      cerebrovascular, or hepatic events associated with desvenlafaxine 100 mg/day. The
      meta-analysis suggests that treatment with desvenlafaxine 100 mg/day is
      associated with a significant reduction of moderate to severe hot flashes in
      postmenopausal women. Desvenlafaxine appears both safe and effective for treating
      hot flushes for up to 12 months.

PMID- 23548359
TI  - Pathology and causes of death of stranded cetaceans in the Canary Islands (1999
      2005).
AB  - Between 1999 and 2005, 233 stranded cetaceans (comprising 19 species) were
      reported in the waters of the Canary Islands. Of these, 138/233 (59.2%) were
      subjected to a complete or partial standardized necropsy, including 4
      Balaenopteridae, 9 Physeteridae, 8 Kogiidae, 27 Ziphiidae and 90 Delphinidae. Of
      these, 46/138 (33.3%) cetaceans were diagnosed with anthropogenic pathological
      categories (i.e. the cause of death was anthropogenic). These included fishing
      interaction (bycatch) (19 individuals), 'atypical' mass stranding events linked
      to naval exercises (13), ship collisions (8) and other anthropogenic-related
      pathology (6). 'Natural' (i.e. non-anthropogenic) causes of death accounted for
      another 82/138 (59.4%) cases, including infectious and non-infectious diseases
      (63), neonatal pathology (8), intra- and interspecific interactions (6) and mass
      strandings (5). The cause(s) of death could not be determined in 10/138 (7.3%)
      necropsied animals. The most common causes of death were ship collisions in 6/9
      (66.6%) Physeteridae, 'atypical' mass stranding linked to naval exercises in
      13/27 (48.1%) Ziphiidae, and 'natural' infectious and non-infectious diseases in
      55/90 (61.1%) Delphinidae. Interaction with fishing activities was established as
      cause of death in 15/90 (16.7%) Delphinidae. These data show that a range of
      anthropogenic and natural single and mass mortality events occur in multiple
      cetacean species stranded in the Canary Islands.

PMID- 23548360
TI  - Factors affecting variation in mortality of marine Atlantic salmon Salmo salar in
      Scotland.
AB  - Databases of site production have an important role to play in the investigation
      and understanding of diseases, since they store valuable amounts of disease and
      management data. Diseases pose an important constraint to economic expansion of
      aquaculture. They are dependent on the complex interacting factors of pathogen,
      environment, and host, and the causes of death can be related to nutritional,
      environmental, and genetic factors of the host or infectious agents. We examined
      the drivers of mortality from a single site-production database, which
      represented one-third of Scottish farmed salmon Salmo salar L. production in
      2005, to determine whether mortality 'benchmarking' data could be generalised
      across sites and production cycles. We show that farm mortality records play an
      important role in studying mortality losses and identifying of management
      problems in production. We found that mortalities varied across the months of the
      year and with the time of year of initial stocking. Production cycles that
      started in the third quarter of the year had the highest mortality overall.
      Furthermore, we found site-to-site variation in mortality that may have been
      caused by either random occurrence of epidemics and environmental events or other
      local effects.

PMID- 23548361
TI  - Structure of Flavobacterium psychrophilum populations infecting farmed rainbow
      trout Oncorhynchus mykiss .
AB  - Flavobacterium psychrophilum isolated from rainbow trout Oncorhynchus mykiss
      suffering from bacterial cold-water disease (BCWD) can dissociate into 2
      morphological colony types, rough (R) and smooth (S). However, the presence of
      the 2 morphotypes in disease outbreaks has not yet been investigated thoroughly.
      We examined the occurrence of R and S morphotypes in rainbow trout from BCWD
      outbreaks and in unfertilized eggs from a hatchery. The isolated colony types
      were characterized by pulsed field gel electrophoresis (PFGE), plasmid analysis,
      and oxolinic acid susceptibility testing. From most outbreaks, both morphotypes
      were isolated, although the S type only was isolated from the majority of
      individual fish. PFGE analysis showed both diverse and indistinguishable genetic
      patterns among the concurrent morphotypes. While PFGE patterns common to both
      fish and egg isolates were identified, this was not always the case. Resistant
      and sensitive isolates of both colony types were isolated from individual disease
      outbreaks. The plasmid pattern was partly associated with the colony type,
      showing identical or completely different patterns for the R and S types isolated
      from the same outbreak. The study showed that within a BCWD outbreak, F.
      psychrophilum cells with different morphology, plasmid content, antibiotic
      susceptibility, and PFGE pattern can be isolated, suggesting that F.
      psychrophilum populations infecting rainbow trout in farm environments can be
      diverse and thus complicate the control of the disease.

PMID- 23548362
TI  - Involvement of the cell-specific pigment genes pks and sult in bacterial defense
      response of sea urchins Strongylocentrotus intermedius.
AB  - Bacterial infections are one of the most important problems in mass aquaculture,
      causing the loss of millions of juvenile organisms. We isolated 22 bacterial
      strains from the cavity fluid of the sea urchin Strongylocentrotus pallidus and
      used phylogenetic analysis based on 16S rRNA gene sequences to separate the
      bacterial strains into 9 genera (Aliivibrio, Bizionia, Colwellia, Olleya,
      Paenibacillus, Photobacterium, Pseudoalteromonas, Shewanella, and Vibrio).
      Incubating Strongylocentrotus intermedius larvae with a strain from each of the 9
      bacterial genera, we investigated the viability of the larvae, the amount of
      pigment cells, and the level of polyketide synthase (pks) and sulfotransferase
      (sult) gene expression. Results of the assay on sea urchin development showed
      that all bacterial strains, except Pseudoalteromonas and Bizionia, suppressed sea
      urchin development (resulting in retardation of the embryos' development with
      cellular disorders) and reduced cell viability. We found that pks expression in
      the sea urchin larvae after incubation with the bacteria of 9 tested genera was
      significantly increased, while the sult expression was increased only after the
      treatment with Pseudoalteromonas and Shewanella. Shikimic acid, which is known to
      activate the biosynthesis of naphthoquinone pigments, increased the tolerance of
      the sea urchin embryos to the bacteria. In conclusion, we show that the cell
      specific pigment genes pks and sult are involved in the bacterial defense
      response of sea urchins.

PMID- 23548363
TI  - Identification and characterization of Vibrio harveyi associated with diseased
      abalone Haliotis diversicolor.
AB  - Mass mortality of farmed small abalone Haliotis diversicolor occurred in Fujian,
      China, from 2009 to 2011. Among isolates obtained from moribund abalones, the
      dominant species AP37 exhibited the strongest virulence. After immersion
      challenge with 106 CFU ml-1 of AP37, abalone mortalities of 0, 53 and 67% were
      induced at water temperatures of 20 degrees C, 24 degrees C, and 28 degrees C,
      respectively. Following intramuscular injection, AP37 showed a low LD50 (median
      lethal concentration) value of 2.9 * 102 CFU g-1 (colony forming units per gram
      abalone wet body weight). The LT50 (median lethal time) values were 5.2 h for 1 *
      106 CFU abalone-1, 8.4 h for 1 * 105 CFU abalone-1, and 21.5 h for 1 * 104 CFU
      abalone-1. For further analysis of virulence, AP37 was screened for the
      production of extracellular factors. The results showed that various factors
      including presence of flagella and production of extracellular enzymes, such as
      lipase, phospholipase and haemolysin, could be responsible for pathogenesis.
      Based on its 16S rRNA gene sequence, strain AP37 showed >98.8% similarity to
      Vibrio harveyi, V. campbellii, V. parahaemolyticus, V. alginolyticus, V.
      natriegens and V. rotiferianus, so it could not be identified by this method.
      However, multi-locus sequence analysis (MLSA) of concatenated sequences,
      including the rpoD, rctB, gyrB, toxR and pyrH genes, identified strain AP37 as V.
      harveyi. Phenotypic characters of AP37 were identified by API 20E. In antibiotic
      susceptibility tests, strain AP37 exhibited susceptibility to 7 antibiotics and
      resistance to 13. This is the first report of a V. harveyi-related species being
      linked with the mass mortality of adult abalone H. diversicolor in southern
      China.

PMID- 23548364
TI  - Culture-independent analysis of bacterial communities in hemolymph of American
      lobsters with epizootic shell disease.
AB  - Epizootic shell disease (ESD) of the American lobster Homarus americanus H. Milne
      Edwards, 1837 is a disease of the carapace that presents grossly as large,
      melanized, irregularly shaped lesions, making the lobsters virtually unmarketable
      because of their grotesque appearance. We analyzed the bacterial communities
      present in the hemolymph of lobsters with and without ESD using nested-PCR of the
      16S rRNA genes followed by denaturing gradient gel electrophoresis. All lobsters
      tested (n = 42) had bacterial communities in their hemolymph, and the community
      profiles were highly similar regardless of the sampling location or disease
      state. A number of bacteria were detected in a high proportion of samples and
      from numerous locations, including a Sediminibacterium sp. closely related to a
      symbiont of Tetraponera ants (38/42) and a Ralstonia sp. (27/42). Other bacteria
      commonly encountered included various Bacteroidetes, Pelomonas aquatica, and a
      Novosphingobium sp. One bacterium, a different Sediminibacterium sp., was
      detected in 20% of diseased animals (n = 29), but not in the lobsters without
      signs of ESD (n = 13). The bacteria in hemolymph were not the same as those known
      to be present in lesion communities except for the detection of a Thalassobius
      sp. in 1 individual. This work demonstrates that hemolymph bacteremia and the
      particular bacterial species present do not correlate with the incidence of ESD,
      providing further evidence that microbiologically, ESD is a strictly cuticular
      disease. Furthermore, the high incidence of the same species of bacteria in
      hemolymph of lobsters may indicate that they have a positive role in lobster
      fitness, rather than in disease, and further investigation of the role of
      bacteria in lobster hemolymph is required.

PMID- 23548365
TI  - Self-limiting outbreak of crayfish plague in an Austropotamobius pallipes
      population of a river basin in the Abruzzi region (central Italy).
AB  - Crayfish plague, caused by the oomycete Aphanomyces astaci, is a serious disease
      of European freshwater crayfish and has eliminated entire populations in several
      European countries. In September 2011, mortality was observed among the
      Austropotamobius pallipes population of a river basin in the Abruzzi region
      (central Italy), and A. astaci DNA was detected by PCR in dead crayfish. A
      systematic survey was carried out to evaluate the spread and the effects of the
      plague in the river basin. The source of the outbreak remained unknown since
      North American crayfish species, which frequently act as subclinical carriers of
      the infection, were not detected in the area. The A. pallipes population
      disappeared from a river stretch of ~1 km, where A. astaci infection was detected
      in dead crayfish. However, apparently unaffected crayfish were still present
      upstream of that area as well as in a tributary that joined the brook in the
      apparently depopulated stretch. A. astaci infection was not detected in dead
      individuals collected in the upstream area and tributary. A follow-up visit
      conducted in the following season showed the presence of A. pallipes in the river
      stretch hit by the plague. In this outbreak, the spread of the infection could
      have been limited by a low density of the crayfish population and by the
      geographic conformation of the river basin, which includes a dense network of
      small tributaries, characterized by high flow velocity and low water temperature.
      In this particular setting, crayfish plague outbreaks can remain undetected. This
      underlines the importance of active monitoring programs aimed at the prompt
      recognition of both episodes of mortality and the presence of non-indigenous
      crayfish species.

PMID- 23548366
TI  - Aphanomyces astaci in wild crayfish populations in Slovenia: first report of
      persistent infection in a stone crayfish Austropotamobius torrentium population.
AB  - All 5 crayfish species inhabiting Slovenian freshwaters, of which 3 are
      indigenous crayfish species (ICS: Astacus astacus, Austropotamobius pallipes, and
      A. torrentium) and 2 are non-indigenous (NICS: Pacifastacus leniusculus and
      Cherax quadricarinatus), were inspected for the presence of Aphanomyces astaci,
      the causative agent of crayfish plague. Wild crayfish populations showing no
      clinical signs of infection were inspected using A. astaci-specific real-time
      PCR. In addition, a conventional PCR assay was employed and confirmative
      sequencing was performed. Out of 88 analyzed crayfish, 15/27 (55.6%) specimens of
      A. torrentium from Borovnisc%%KERN_ERR%%ica Brook and 4/35 (11.4%) of P.
      leniusculus from the Mura River tested positive, showing low to moderate levels
      of infection (agent levels A1-A4 and A1-A3, respectively). Results revealed the
      presence of A. astaci not only in the resistant NICS but also in ICS, since the
      infected population of A. torrentium presumably had no contact with the NICS
      carrier and appeared to sustain A. astaci infection in the 2 sampling years.
      Although the A. astaci genotype has not yet been identified, a connection between
      the latent infection in ICS and a Group A strain of A. astaci, co-evolving with
      A. torrentium since its first introduction to Slovenia, is suggested as the most
      plausible conclusion. This is the first reported population of the genus
      Austropotamobius with persistent infection, in addition to the already known
      populations of the genus Astacus. Findings of the presumed co-evolution of A.
      astaci and ICS hosts open new perspectives, necessitating additional studies on
      the presence of A. astaci genotypes in the persistently infected ICS populations.

PMID- 23548367
TI  - Trends, risk factors and outcomes of healthcare-associated infections within the
      Italian network SPIN-UTI.
AB  - BACKGROUND: Implementing infection control measures in light of healthcare
      associated infection (HAI) surveillance data can prevent HAIs. Surveillance has
      been associated with a reduction of HAI in intensive care unit (ICU) patients,
      though the reasons for this improvement remain unclear. AIM: To evaluate changes
      in healthcare-associated infection (HAI) rates during three surveys of the
      Italian Nosocomial Infections Surveillance in Intensive Care Units (ICUs) network
      (SPIN-UTI) six-year project and to explore sources of variation of indicators of
      HAI in the 65 participating ICUs. METHODS: The SPIN-UTI network adopted the
      European protocols for patient-based HAI surveillance. Cumulative incidence,
      incidence density, infection rates adjusted for device-days, and device
      utilization ratios were calculated for each survey and compared. To identify risk
      factors multiple logistic regression analyses were performed. Crude excess
      mortality was computed as the difference between the crude overall case-fatality
      rate of patients with and without HAI. FINDINGS: The risk of ICU-acquired
      infections increased in the third survey compared with previous (relative risk:
      1.215; 95% confidence interval: 1.059-1.394). Among risk factors, the number of
      hospitalized patients requiring ICU admission and the Simplified Acute Physiology
      Score II increased from 73.7% to 78.1% and from 37.9% to 40.8% respectively.
      Although mortality rates remained unchanged, HAIs trebled the risk of death.
      Acinetobacter baumannii was the most frequently reported micro-organism in the
      third survey (16.9%), whereas in the previous surveys it ranked third (7.6%) and
      second (14.3%). CONCLUSIONS: The study highlighted the increased risk of HAI, at
      least partially explained by the greater severity and number of hospitalized
      patients requiring ICU admission. Furthermore, the management of intubation
      procedures and of ventilated patients was identified as a potential target for
      infection control interventions to decrease the growing risk of HAI in ICUs.

PMID- 23548368
TI  - The impact of endocrine disruption: a consensus statement on the state of the
      science.

PMID- 23548369
TI  - Should bone scan be performed in Chinese prostate cancer patients at the time of
      diagnosis?
AB  - BACKGROUND: Prostate cancer (PCa) is increasingly being diagnosed in China. Early
      detection of bone metastases (BM) is critical in the management of patients with
      high-risk PCa. The aim of this study is to establish a screening model to
      determine if bone scan should be performed for BM in Chinese patients at the time
      when PCa is diagnosed. MATERIALS AND METHODS: The study included 488 patients who
      were diagnosed with PCa between 2009 and 2011 at a single center. All patients
      received bone scans using technetium (99m)Tc methylene diphosphonate at the
      initial staging. If the bone scan finding was equivocal, computed tomography or
      magnetic resonance imaging was performed to confirm the diagnosis. Age, prostate
      specific antigen (PSA) at diagnosis, clinical stage assigned according to the TNM
      2002 staging system and biopsy Gleason score were collected in all patients.
      Multivariate logistic regression analysis was performed to identify statistically
      significant covariates and then receiver operating characteristic (ROC) curves
      were generated to identify optimal cut-off values. Using these cut-off values, a
      formula was devised to calculate an index value for BM screening at diagnosis.
      The model was cross-validated using the leave-one-out method. RESULTS: Of the 488
      patients, 65 patients (13.3%) had BM. The area under the ROC curve was 0.87 (95%
      confidence interval 0.83-0.94). The sensitivity of the cut-off point was 87.7%
      and the specificity was 73.1%. Bone scan is needed for all cT4 PCa patients,
      however, it is also advisable for cT1-T3 PCa patients who have a biopsy Gleason
      score <=3 + 4 and a PSA >132.1, and for cT1-T3 patients having a Gleason score of
      >=4 + 3 and PSA >44.5. CONCLUSIONS: The regression model may help determine if
      bone scan is needed to detect BM from PCa at the time of diagnosis. The model was
      generated upon a single center experience. Further validation is needed in future
      studies.

PMID- 23548370
TI  - Cells co-expressing luteinising hormone and thyroid-stimulating hormone are
      present in the ovine pituitary pars distalis but not the pars tuberalis:
      implications for the control of endogenous circannual rhythms of prolactin.
AB  - BACKGROUND/AIMS: A mammalian circannual pacemaker responsible for regulating the
      seasonal pattern of prolactin has been recently described in sheep. This
      pacemaker resides within the pars tuberalis, an area of the pituitary gland that
      densely expresses melatonin receptors. However, the chemical identity of the cell
      type which acts as the pacemaker remains elusive. Mathematical-modelling
      approaches have established that this cell must be responsive to the static
      melatonin signal as well as prolactin negative feedback. Considering that in
      sheep the gonadotroph is the only cell in the pars tuberalis which expresses the
      prolactin receptor, and that in other photoperiodic species the thyrotroph is the
      only cell expressing the melatonin receptor in this tissue, a cell type which
      expresses both proteins would fulfil the theoretical criteria of a circannual
      pacemaker. METHODS: Pituitary glands were obtained from female sheep under short
      days (breeding season) and long days (non-breeding season) and double
      immunofluorescent staining was conducted to determine the prevalence of bi
      hormonal cells in the pars distalis and pars tuberalis using specific antibodies
      to luteinising hormone-beta and thyroid-stimulating hormone-beta. RESULTS: The
      results reveal that whilst such a bihormonal cell is clearly present in the pars
      distalis and constitute 4% of the gonadotroph population in this region, the same
      cell type is completely absent from the pars tuberalis even though LH
      gonadotrophs are abundantly expressed. CONCLUSIONS: Based on these findings,
      together with existing data, we are able to propose an alternative model where
      the gonadotroph itself is controlled indirectly by neighbouring melatonin
      responsive cells, allowing it to act as a pacemaker.

PMID- 23548372
TI  - Impact of peripheral arterial occlusive disease on the development of contrast
      medium-induced acute kidney injury.
AB  - BACKGROUND/AIMS: Contrast medium-induced acute kidney injury (CI-AKI) is an
      important complication following the use of iodinated contrast media. It accounts
      for a significant number of hospital-acquired acute kidney injuries and is
      associated with increased in-hospital and long-term mortality and immense health
      care costs. We evaluated whether the presence of peripheral arterial occlusive
      disease (PAD) affects the incidence of CI-AKI following heart catheterization.
      METHODS: The impact of PAD on the frequency of CI-AKI after heart catheterization
      was analysed in the prospective single-centre Dialysis-versus-Diuresis trial
      (January 2001 to July 2004). The patients were retrospectively divided into 3
      subgroups: patients with coronary heart disease (CHD), patients with PAD and
      patients without PAD or CHD. RESULTS: 412 patients were included (83.5% men,
      29.1% diabetes mellitus, 4.9% ejection fraction <35%). Of these, 251 (60.9%)
      suffered from CHD but not from PAD, 77 (18.7%) from PAD and 84 (20.4%) had
      neither CHD nor PAD. After heart catheterization, 49 (11.9 %) patients developed
      CI-AKI. Patients with PAD suffered significantly more often from CI-AKI than
      those without PAD (32.7 vs. 16.8%, p = 0.008). Multivariate analyses by logistic
      regression confirmed PAD to be an independent predictor of a CI-AKI (odds ratio
      2.013, 95% confidence interval 1.009-4.016, p = 0.047). The CHD was not
      significantly associated with CI-AKI. CONCLUSION: Patients with PAD significantly
      more often develop a CI-AKI after heart catheterization than those without PAD.

PMID- 23548373
TI  - Introducing the productive operating theatre programme in urology theatre suites.
AB  - BACKGROUND: The Productive Operating Theatre (TPOT) is a theatre improvement
      programme designed by the UK National Health Service. The aim of this study was
      to evaluate the implementation of TPOT in urology operating theatres and identify
      obstacles to running an ideal operating list. METHOD: TPOT was introduced in two
      urology operating theatres in September 2010. A multidisciplinary team identified
      and audited obstacles to the running of an ideal operating list. A brief/debrief
      system was introduced and patient satisfaction was recorded via a structured
      questionnaire. The primary outcome measure was the effect of TPOT on start and
      overrun times. RESULTS: Start times: 39-41% increase in operating lists starting
      on time from September 2010 to June 2011, involving 1,365 cases. Overrun times:
      Declined by 832 min between March 2010 and March 2011. The cost of monthly
      overrun decreased from September 2010 to June 2011 by GBP 510-3,030. Patient
      experience: A high degree of satisfaction regarding level of care (77%), staff
      hygiene (71%) and information provided (72%), while negative comments regarding
      staff shortages and environment/facilities were recorded. CONCLUSIONS: TPOT has
      helped identify key obstacles and shown improvements in efficiency measures such
      as start/overrun times.

PMID- 23548374
TI  - Switching from carvedilol to bisoprolol ameliorates adverse effects in heart
      failure patients with dizziness or hypotension.
AB  - BACKGROUND: Treatment with carvedilol is an established primary therapy for
      patients with heart failure (HF). However, its most common adverse effects,
      dizziness and hypotension, often discourage continuation or dosage increase. The
      aim of this study was to examine whether switching to bisoprolol from carvedilol
      would help to avoid adverse symptoms and signs related to carvedilol
      administration. METHODS AND SUBJECTS: Data were retrospectively collected from 23
      patients with HF [age 57+/-18 years, left ventricular ejection fraction (LVEF)
      33+/-15%] who could not increase the dosage of carvedilol because of dizziness or
      hypotension, defined as systolic blood pressure<90 mmHg. Before and immediately
      after, and 6 months after switching to bisoprolol, we examined symptoms, vital
      signs, laboratory data, and New York Heart Association functional class.
      Furthermore, left ventricular (LV) dimension and ejection fraction (EF) were
      evaluated in 19 patients using echocardiography. RESULTS: All 13 patients with
      dizziness (100%) and 9 of 16 with hypotension (56%) were relieved of adverse
      symptoms or signs. The mean dose of carvedilol before switching was 5.60+/-3.43
      mg. Immediately after the switch, the mean dose of bisoprolol was 1.84+/-1.08 mg
      and then increased to 3.13+/-1.74 mg after 6 months (p<0.01). At 6-month follow
      up examinations, LV function determined by LVEF was significantly improved, which
      was accompanied by increased exercise tolerance. CONCLUSION: Switching from
      carvedilol to bisoprolol may help with continuation of beta-blocker treatment as
      well as dosage increase in HF patients with adverse symptoms or signs, allowing
      them to reach the target dose.

PMID- 23548375
TI  - Autophagy is involved in endoplasmic reticulum stress-induced cell death of rat
      hepatocytes.
AB  - BACKGROUND: Both endoplasmic reticulum (ER) stress and autophagy have been shown
      to display dual roles in cell survival in multiple cell lines. There is a
      reported but poorly understood link between ER stress, autophagy, and cell death.
      We hypothesized that autophagy plays a role in ER stress-dependent cell death in
      rat hepatocytes. MATERIALS AND METHODS: Primary hepatocytes isolated from both
      lean and obese male Zucker rats were cultured and treated with tunicamycin (TM),
      tauroursodeoxycholic acid, 3-methyladenine, and wortmannin for 12 h. The ER
      stress-associated genes glucose-regulated protein 78 and C/EBP homologous protein
      were examined via quantitative real time polymerase chain reaction.
      Immunostaining with microtubule-associated protein 1 light chain 3 as well as
      electron microscopy were used to evaluate autophagy activity. Trypan blue
      exclusion was used to determine hepatocyte cell viability. RESULTS: In both lean
      and steatotic hepatocytes, we found that TM induced both C/EBP homologous protein
      and glucose-regulated protein 78 messenger RNA expression. Cells with increased
      ER stress were undergoing increased autophagy and had a significant decrease in
      cell viability. Both tauroursodeoxycholic acid and 3-methyladenine treatments
      attenuated TM induced ER stress, autophagy, and cell death, whereas wortmannin
      treatment reduced autophagy and cell death but without changing ER stress.
      CONCLUSIONS: These data suggest that autophagy is a likely downstream mediator of
      ER stress-induced cell death in rat hepatocytes. Further exploration of the link
      between autophagy and ER stress in hepatocyte injury will yield important
      information that may be leveraged for treatment of liver injuries such as
      ischemia/reperfusion.

PMID- 23548376
TI  - Oxacillin resistance and antimicrobial susceptibility profile of Staphylococcus
      saprophyticus and other staphylococci isolated from patients with urinary tract
      infection.
AB  - BACKGROUND: Staphylococcus saprophyticus is the second most frequent community
      acquired causative agent of urinary tract infection (UTI). The objective of this
      study was to evaluate the susceptibility profile and resistance detection in
      Staphylococcus species. isolated from patients with UTI. MATERIALS AND METHODS:
      The isolates were investigated using the disk diffusion method, Vitek I system, E
      test(r), and detection of the mecA gene. RESULTS: Most isolates (76.2%) were
      resistant to oxacillin by the disk diffusion method, followed by those resistant
      to penicillin (72.2%). The oxacillin disk diffusion method, E-test, and Vitek I
      method showed higher sensitivity (94.4%) and lower specificity (28.9, 26.5, and
      24.0%, respectively) than the cefoxitin disk diffusion test (sensitivity: 83.5%,
      specificity: 85.5%) for the detection of oxacillin resistance. CONCLUSIONS: The
      large number of oxacillin-resistant isolates indicates that the breakpoint value
      recommended by the Clinical and Laboratory Standards Institute may overestimate
      oxacillin resistance in S. saprophyticus. Thus, changes in these guidelines are
      necessary for the correct detection of this resistance.

PMID- 23548377
TI  - Comparison between the intraoperative use of polyvinyl chloride cover and
      surgical compresses for preventing postoperative adhesions.
AB  - BACKGROUND/PURPOSE: Surgical compresses used for retraction during major
      abdominal and pelvic procedures lead to postoperative adhesion formation
      resulting from damage to the visceral peritoneum. This study investigates whether
      polyvinyl chloride (PVC) covers cause less postsurgical adhesion and inflammation
      than surgical compresses in an animal model. METHODS: Female Wistar albino rats
      (n = 160) were divided into three groups (compress, PVC cover and control), which
      were then divided into 16 subgroups (n = 10/group). All animals underwent midline
      laparotomy and cecal abrasion. A metal retractor, which applies a constant force,
      was then placed on the small intestine for 2 h. In the control group, no material
      was placed under the retractor, whereas a surgical compress or PVC cover was
      placed in the experimental animals. Full-thickness small intestinal biopsies were
      obtained and examined by light and electron microscopy. The following parameters
      were evaluated: congestion, mesothelial proliferation, leukocyte migration and
      collagenization. Adhesions were scored according to the Nair, Knightly and Mazuji
      scoring systems. RESULTS: All inflammation scores were significantly higher in
      the compress group than in the other two groups. However, no significant
      difference was observed between the PVC cover and control groups. Adhesions were
      more frequent in the compress group than in the other two groups, regardless of
      the scoring system used. CONCLUSIONS: Surgical compresses used in abdominal and
      pelvic surgeries cause inflammation and adhesion. Contrary to surgical
      compresses, PVC covers do not cause inflammation and adhesion, which may
      considerably reduce adhesion-related complications in abdominopelvic surgeries.

PMID- 23548378
TI  - Enhancing sleep quality and memory in insomnia using instrumental sensorimotor
      rhythm conditioning.
AB  - EEG recordings over the sensorimotor cortex show a prominent oscillatory pattern
      in a frequency range between 12 and 15 Hz (sensorimotor rhythm, SMR) under quiet
      but alert wakefulness. This frequency range is also abundant during sleep, and
      overlaps with the sleep spindle frequency band. In the present pilot study we
      tested whether instrumental conditioning of SMR during wakefulness can enhance
      sleep and cognitive performance in insomnia. Twenty-four subjects with clinical
      symptoms of primary insomnia were tested in a counterbalanced within-subjects
      design. Each patient participated in a SMR- as well as a sham-conditioning
      training block. Polysomnographic sleep recordings were scheduled before and after
      the training blocks. Results indicate a significant increase of 12-15 Hz activity
      over the course of ten SMR training sessions. Concomitantly, the number of
      awakenings decreased and slow-wave sleep as well as subjective sleep quality
      increased. Interestingly, SMR-training enhancement was also found to be
      associated with overnight memory consolidation and sleep spindle changes
      indicating a beneficial cognitive effect of the SMR training protocol for SMR
      "responders" (16 out of 24 participants). Although results are promising it has
      to be concluded that current results are of a preliminary nature and await
      further proof before SMR-training can be promoted as a non-pharmacological
      approach for improving sleep quality and memory performance.

PMID- 23548379
TI  - Intravitreal bevacizumab for radiation-induced cystoid macular oedema in patients
      with nasopharyngeal carcinoma: a clinical series.
AB  - AIMS: To evaluate the outcome of intravitreal bevacizumab in the treatment of
      radiation-induced cystoid macular oedema among patients who underwent external
      beam radiotherapy for nasopharyngeal carcinoma. METHODS: Five patients were
      recruited. The length of time from the last external beam radiation therapy to
      presentation ranged from 12 months to 15 years. Intravitreal bevacizumab (1.25
      mg/0.05 ml) was given and repeated monthly injections were administered until
      best corrected visual acuity (BCVA) improved to 6/9 or until 3 further injections
      did not show further improvement in BCVA. BCVA was measured and fundus
      photography, optical coherence tomography (OCT) and fluorescein angiography were
      performed at baseline. BCVA and OCT were recorded at each monthly visit. The
      duration of follow-up ranged from 6 months to 2 years. RESULTS: Five patients (7
      eyes) were recruited. At the final visit, 3 eyes (71.4%) showed reduction in the
      central subfield thickness (CST; mean reduction of 17.6%, range 9-149 um) with
      improvement in BCVA, whilst 2 eyes worsened in terms of CST and final BCVA.
      Another 2 eyes remained altered in BCVA despite slight improvement in CST.
      CONCLUSION: The use of intravitreal bevacizumab in this group of patients showed
      variable response in terms of CST and BCVA outcome but remains a viable option to
      treat this challenging condition.

PMID- 23548380
TI  - Magnitude of end-dialysis overweight is associated with all-cause and
      cardiovascular mortality: a 3-year prospective study.
AB  - BACKGROUND: We hypothesized that the difference between the prescribed end
      dialysis body weight, defined end-dialysis over-weight (edOW; kg), and the body
      weight which is actually attained could impact survival in hemodialysis (HD)
      patients. The aim of this prospective observational study was to evaluate if edOW
      could influence survival in a cohort of prevalent HD patients, controlled for
      multiple dialysis and clinical risk factors and followed for 3 years. METHODS:
      One hundred and eighty-two patients (117 men, age 65 +/- 13 years) on regular HD
      treatment for at least 6 months [median 48 months (range: 6-366)] were followed
      from January 1, 2008 to December 31, 2010. Eighty-four patients (46%) did not
      achieve their prescribed dry body weight (dBW); their median edOW was 0.4 kg
      (range: 0.1-1.4). Ninety-eight died during observation, mainly from
      cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized
      to evaluate the effect edOW, ultrafiltration rate (UFR), interdialytic weight
      gain (IDWG), age, sex, dialytic vintage, cardiovascular disease, antihypertensive
      therapy, diabetes, duration of HD, dBW, BMI, mean arterial blood pressure, Kt/V,
      and protein catabolic rate (PCRn) had on mortality. RESULTS: Age (HR: 1.04; CI:
      1.03-1.05; p <0.0001), IDWG (HR: 2.62; CI: 2.06-3.34; p < 0.01), UFR (HR: 1.13;
      CI: 1.09-1.16; p< 0.01), PCRn (HR: 0.02; CI: 0.01-0.04; p <0.001), and edOW (HR:
      2.71; CI: 1.95-3.75; p < 0.02) were independently correlated to survival. The
      relative receiver operating characteristic curve identified a cutoff value of 0.3
      kg for edOW in predicting death. CONCLUSIONS: High edOW is independently
      associated with an increased long-term risk of all-cause and cardiovascular
      mortality in HD patients. Better survival was observed in patients with edOW <0.3
      kg. For patients with higher edOW, longer or more frequent dialysis sessions
      should be considered in order to prevent the deleterious consequences of
      excessive body fluid expansion.

PMID- 23548381
TI  - Simulation of XPS C1s spectra of organic monolayers by quantum chemical methods.
AB  - Several simple methods are presented and evaluated to simulate the X-ray
      photoelectron spectra (XPS) of organic monolayers and polymeric layers by density
      functional theory (DFT) and second-order Moller-Plesset theory (MP2) in
      combination with a series of basis sets. The simulated carbon (C1s) XPS spectra
      as obtained via B3LYP/6-311G(d,p) or M11/6-311G(d,p) calculations are in good
      agreement (average mean error <0.3 eV) with the experimental spectra, and good
      estimates of C1s spectra can be obtained via E(C1s)(exp) = 0.9698EC1s(theory) +
      20.34 (in eV) (B3LYP/6-311G(d,p)). As a result, the simulated C1s XPS spectra can
      elucidate the binding energies of the different carbon species within an organic
      layer and, in this way, greatly aid the assignment of complicated C1s XPS
      spectra. The paper gives a wide range of examples, including haloalkanes, esters,
      (thio-)ethers, leaving groups, clickable functionalities, and bioactive moieties.

PMID- 23548382
TI  - Characterization of hip passive stiffness of volleyball, basketball and futsal
      young athletes.
AB  - OBJECTIVES: (1) To establish the reference values of the test of 'Position of hip
      passive resistance against gravity' (PHPR) in young athletes; (2) To investigate
      differences between the values of PHPR test according to athlete's sex, age and
      sport practiced. DESIGN: Cross-sectional. SETTING: Sports club. PARTICIPANTS: 282
      Volleyball, basketball and futsal athletes aged between 10 and 18 years. MAIN
      OUTCOME MEASURES: Hip passive stiffness was measured through PHPR test, which
      provides indirect information regarding this tissue property; high stiffness
      means low corresponding test values. RESULTS: The mean values of PHPR test ranged
      from 0.41 to 1.06 degrees /kg. The test results were different among all age
      categories and the values were lower in older athletes (p<0.001). The PHPR test
      values of futsal players were lower than basketball players only in the
      intermediate age category (p=0.001). The female volleyball athletes had higher
      values than the male ones (p<0.001). CONCLUSION: This study established reference
      values for PHPR test in young athletes, which allow therapists to obtain
      information regarding hip passive stiffness by means of a clinical test. Hip
      passive stiffness in young athletes increases with age, and female volleyball
      players showed lower values of this property compared with males.

PMID- 23548384
TI  - [Characteristic of the complement system in patients with ischemic heart disease
      with moderate and marked hemolysis after operations with cardiopulmonary bypass].
AB  - A study of the complement system in cardiosurgical patients with moderate (40
      patients) and marked (18 patients) hemolysis after coronary artery bypass
      grafting in conditions of cardiopulmonary bypass was carried out. Before and
      after operation the content of D35+-, D55+-erythrocytes and reticulocytes in
      blood, free hemoglobin in blood plasma, indicators of the functional state of
      classical, lectin and alternative pathways of complement activation as well as
      concentration of its terminal complex in blood serum were analyzed. It was
      established that development of marked hemolysis was associated with higher
      (compared with moderate hemolysis) content of terminal complement complex and
      reticulocytes in blood before operation as well as deficiency of D55+-
      erythrocytes and low activity of alternative pathway.

PMID- 23548383
TI  - Safety and immunogenicity of a DNA vaccine encoding human calcium-activated
      chloride channel 1 (hCLCA1) in asthmatic mice.
AB  - BACKGROUND: Calcium-activated chloride channels (CLCAs) have been found to be
      preferentially expressed on the secretory epithelium. They may play a pivotal
      role in mucous overproduction by bronchial goblet cells in asthma. It has been
      reported that the inhibition of CLCAs with niflumic acid could relieve the
      symptoms of asthma. However, niflumic acid has serious adverse effects. DNA
      vaccination is considered to be a promising strategy to treat allergic diseases
      such as asthma and dust mite allergy. METHODS: We constructed a vaccine encoding
      human CLCA1 (hCLCA1) and evaluated its effects on promoting antibodies against
      hCLCA1 and the related preventive function in a mouse model of asthma. RESULTS:
      Our results reveal that the induced hCLCA1 antibodies can be detected in the
      first 2 weeks after immunization with hCLCA1 plasmids (hCLCA1-p) by intramuscular
      injection and augmented gradually in the following several weeks. The
      autoantibodies against hCLCA1 induced by the DNA vaccine bound to three segments
      of the mouse CLCA3 (mCLCA3) protein, including the amino terminal (PepN), the
      carboxyl terminal (PepC) and the middle of the protein (PepM). In our study, mice
      immunized with hCLCA1-p developed fewer pathological changes compared with other
      control groups, including a remarkable reduction in the air pressure-time index
      of the trachea, the number of eosinophils and mast cells in the bronchoalveolar
      lavage fluid and the mRNA level of MUC5AC in goblet cells. CONCLUSION: Taken
      together, our results suggest that a DNA vaccine encoding the CLCA protein may
      have potential as a useful pharmacotherapy for asthma in the future.

PMID- 23548385
TI  - [The role of multispiral computed tomography in assessment of viability of the
      myocardium and prognostication of left ventricular remodeling in patients with ST
      elevation myocardial infarction].
AB  - Aim of the study was to assess perfusion defect and viability of the myocardium
      by the method of multispiral computed tomography (MSCT) in patients with ST
      elevation acute myocardial infarction (AMI) and to assess their prognostic role
      in development of remodeling of the left ventricle (LV). We included into the
      study 117 patients with AMI. MSCT with intravenous contrast enhancement was
      carried out on days 3-4 and at 12 months after AMI. In the arterial phase we
      estimated volume of myocardial perfusion defect, LV end diastolic and end
      systolic volumes (LVEDV and LVESV), and LV ejection fraction (EF). Three types of
      myocardial opacification were distinguished on tomograms in delayed phase of
      MSCT: type I - subendocardial residual defect (RD), type II - transmural RD, type
      III - transmural delayed hyper enhancement (DE). Patients were divided in 3
      groups: (1) with subendocardial RD (n=63), (2) with transmural RD (n=28), (3)
      with transmural DE (n=26). Development of LV remodeling was registered if at
      repeat MSCT LVEDV increased more or equal 20% from baseline. In patients with
      signs of viable myocardium (group 1) volume of perfusion defect was substantially
      smaller than in patients with nonviable myocardium (groups 2 and 3): 1cm3 (0.4
      2.4) vs. 7.3 cm3 (5.3-10.0) and 6.3 cm3 (5.0-15.0), respectively, p<0.001.
      Compared with groups 2 and 3 patients of group 1 more often were female (p=0.04),
      had inferior MI (p<0.001), and spontaneous reperfusion (p<0.001). After 12 months
      LV remodeling was registered in 19.3% of patients, all had signs of nonviable
      myocardium in more or equal 3 LV segments. In patients with perfusion defect more
      or equal 10 cm3 probability of development of LV remodeling exceeded 50%.
      Disturbances of perfusion abnormalities and number of nonviable LV segments were
      main predictors of LV remodeling.

PMID- 23548386
TI  - [Prognosis of hospital mortality in patients with acute decompensation of chronic
      heart failure].
AB  - We assessed prognostic value of clinical-laboratory and instrumental parameters
      in 100 patients with acute decompensation of chronic heart failure (CHF) in
      relation to hospital mortality. Independent predictors of lethal outcome in
      patients with acute decompensation of CHF were low systolic arterial pressure at
      admission (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01 to 1.05 per
      each 1 mm Hg of blood pressure lowering), elevation of urea content (OR 1.29,
      95%CI 1.11 to 1.47 per each 1 mmol/L of elevation), potassium (OR 2.09, 95%CI
      1.08 to 4.38 per 1 mmol/L of elevation) and creatinine (OR 1.01, 95%CI 1.01 to
      1.03 per 1 mmol/L of elevation), lowering of glomerular filtration rate (OR 1.29,
      95%CI 1.18 to 1.41 per 1 ml/min/1,73 m2 of lowering), left ventricular dilatation
      (OR 9.53, 95%CI 1.44 to 38.17; =0.043), pulmonary hypertension according to
      echocardiography data (=0.007), scarry changes according to electrocardiography
      data (OR 3.00, 95%CI 1.00 to 10.58; p=0.05), lack of therapy with acetylsalicylic
      acid (OR 6.21, 95%CI 1.62 to 22.73; =0.009) and -adrenoblockers (OR 6.99, 95%CI
      1.39 to 14.49; =0,005) at ambulatory stage.

PMID- 23548387
TI  - [Atrial fibrillation registered for the first time: characteristics of clinical
      course, treatment, prognosis].
AB  - To study the clinical presentation of the first episode of atrial fibrillation
      (AF), treatment tactics and its compliance with current recommendations, features
      of the further clinical course and prognosis in patients with AF we performed a
      retrospective study on data of Polyclinic No 1 of the General Management
      Department of the President of RF . We analyzed data from 58 patients (36 men, 22
      women) from January 2009 to September 2011 inclusive. The first episode of AF was
      recorded in the age from 48 to 90 years (in 39.7% of patients - aged 80 to 90
      years old), mostly had paroxysmal character (84.5%), in 82.1% of cases was
      accompanied by marked clinical symptoms: sense of disruption of the heart (50%),
      feeling short of breath (28.6%), weakness (17.9%). In 87% of cases clinical
      symptomatology required calls for medical emergencies. In 42.9% of cases
      uncontrolled hypertension was possible predisposing factor for developing AF.
      Paroxysmal AF moved to constant in 38.8% of patients during the period from 1
      year to 18 years. Due to the high risk of thromboembolic complications (2 to 5 on
      a scale of CHADS2), after the detection AF warfarin was shown to 96.6% of
      patients, because of the high risk of bleeding in practice was appointed only
      37.9%. Complications of therapy in the form of bleeding were 9.1%. Tactics of
      rhythm control by antiarrhythmic drugs I and III classes has remained in 36.7% of
      patients with paroxysmal AF. -adrenoblockers were constantly taken by 63.3% of
      the patients using antiarrhythmic drugs I and III classes for relief of
      arrhythmia during her recurrence (the strategy of "pill in pocket").

PMID- 23548388
TI  - [Gender related characteristics of clinical status and pharmacotherapy of
      patients with paroxysmal and persistent atrial fibrillation].
AB  - Aim of the study was to elucidate gender related characteristics of clinical
      status and treatment of patients with atrial fibrillation (AF) hospitalized in a
      department of urgent cardiology of multiprofile clinical hospital. In a
      retrospective pharmacoepidemiological study we analyzed case histories of 114 men
      and 79 women hospitalized because of detected and electrocardiografically
      confirmed paroxysmal or persistent AF. Compared to men women were significantly
      older, among them there were significantly more individuals older than 75 years
      (<0.05), and AF developed in women at older age (<0.05). However duration of
      arrhythmic anamnesis was similar in women and men. Among women we noted greater
      prevalence of ischemic heart disease; they had higher risk of thromboembolic
      complications and higher rate of these complications in anamnesis. Rates of
      obesity and diabetes mellitus were also higher among women. Men more often had
      isolated arterial hypertension and lung diseases. There were more smokers among
      men. Women significantly less often received adequate antithrombotic therapy;
      they were less often subjected to electrical cardioversion. Rate control strategy
      was more often selected for women.

PMID- 23548389
TI  - [Effect of angiotensin converting enzyme lisinopril on the state of vascular bed
      in premenopausal women with arterial hypertension].
AB  - We assessed effect of lisinopril on structural-functional state of vascular bed
      in 82 premenopausal women with hypoestrogenia and arterial hypertension (AH).
      Test with postocclusion reactive hyperemia showed that at the background of
      significant lowering of endothelial vasomotor function before treatment 47.5% of
      women had inertial type of vasomotor reaction. This evidenced for considerable
      role of dyshormonal states in progression of AH first of all at the account of
      increase of vascular stiffness and development of endothelial dysfunction.
      Lisinopril improved structural-functional state of vascular wall of common
      carotid arteries, affected positively dysfunction of endothelium, lowered
      stiffness of arterial vascular wall.

PMID- 23548390
TI  - [Spousal concordance of blood pressure levels (results of 17-year follow-up)].
AB  - Study aim was investigation of blood pressure levels (BP) in spouses and
      assessment of the role of arterial hypertension (AH) in a spouse as risk factor
      (RF) of AH in a 17-years prospective study. Primary study based on a random
      sample of citizens of Tomsk (1546 men and women aged 20-59 years) was carried out
      in 1988-1991. At repeat study which was carried out in 2002-2005 we obtained data
      on AH and end points from 81.2% of initial population. Cohort family study
      comprised 427 family couples. Relative risk (RR) of AH development in men in case
      of AH of a female spouse was 1.63 (95% confidence interval [CI] 1.14 to 2.33). RR
      of AH development in a women in this situation was 1.5 (95%CI 1.13 to 1.99).
      Husbands AH was associated with 5.2% elevation of systolic BP (SBP) (<0.001),
      4.8% elevation of diastolic BP (DBP) (=0.001) in his wife. AH of a wife was
      associated with 5.5% elevation of SBP (<0.001) and 5% elevation of DBP (=0.003)
      in a husband. Coefficient of correlation (r) of SBP levels between spouses was
      0.09 in age group 20-39 years (=0.041) and 0.16 in age group 40-59 years
      (=0.002). For DBP in age group 20-39 years r=0.14 (=0.002), in age group 40-59
      years r=0.10 (=0.042). In a prospective study in men and women we found higher
      SBP when AH was detected in a spouse during follow-up compared with individuals
      whose BP had been and remained normal (by 5.4%, =0.015) or those whose BP during
      this period decreased to normal level (by 17.5%; =0.006). Detection of new cases
      of AH in men - spouses of women with AH was higher than in man - cohabitants of
      wives without AH (53.8 and 37.3%, respectively, =0.028). Thus we found
      concordance of BP levels in spouses, which was conditioned by marital assortment
      as well as common environment and way of life.

PMID- 23548391
TI  - [Effect of monotherapy with nebivolol, bisoprolol, carvedilol on the state of
      vegetative nervous system and sexual function in men with arterial hypertension].
AB  - Aim of the study was to assess effect of monotherapy with nebivolol, bisoprolol,
      carvedilol for 2 months on sexual function in men with arterial hypertension
      (AH). Men with 1-2 degree of AH (n=75, age 35-55 years, mean age 48+/-3,5 years)
      received monotherapy with these drugs for 2 months. Registration of parameters of
      heart rate variability (HRV), Dopplerography of penile arteries, and the
      Vasilchenko questionnaire were implemented at the end of 4 months of placebo
      period and after 2 months of therapy with a study drug. Therapy with bisoprolol,
      carvedilol, and nebivolol was associated with significant elevation of
      parasympathetic part of vegetative nervous system tone, improvement of systolic
      blood flow in cavernous and dorsal arteries. Analysis of data obtained by
      Vasilchenko questionnaire demonstrated improvement of psychic and erectile
      components of sexual function. Thus bisoprolol, carvedilol, and nebivolol did not
      worsen sexual function of men with AH, improved spectral parameters of HRV and
      vascular blood flow in arteries of cavernous bodies.

PMID- 23548392
TI  - [Mitral regurgitation and coronary stenosis in postmyocardial infarction
      patients].
AB  - The results of investigations devoted to relationship of mitral regurgitation
      (MR) and scars are contradictive, data on relationship of MR and localization of
      coronary lesions are few. Purpose. To determinate relationship of moderate or
      severe MR to localization of coronary stenosis in postmyocardial infarction
      patients. Methods. There were 1167 patients with no MR and 403 patients with
      moderate or severe MR. Results. Patients with MR had more severe New York Heart
      Association (NYHA) functional class (III-IV) (35.5 vs. 11.2%). Echocardiographic
      indices of left atrial dimension (23.5+/-2.9 vs. 20.3+/-2.1 mm/m) and extent of
      left ventricular (LV) wall motion abnormalities (32.8+/-14.9 vs. 23.6+/-12.7%)
      were higher in patients with MR as well as reduced LV systolic function (LV
      ejection fraction <50% - 63.7 vs. 25.6%) and LV dilatation (63.3 vs. 19.9%, all
      p<0.001). Rates of multivessel coronary artery involvement (three or more
      arteries) (27.5 vs. 18.3%, p=0.001), lesions in left main coronary artery (7.2
      vs. 1.1%), circumflex (36.2 vs. 26.7), and right coronary artery (57.3 vs. 44.9%)
      were higher in patients with MR (all p<0.001). According to results of
      multivariate analysis MR was independently associated with LV dilatation, NYHA
      class of congestive heart failure, index of left atrial size, and extent of LV
      wall motion abnormalities. Moderate or severe chronic MR was not related to
      localization of coronary stenosis in these patients.

PMID- 23548393
TI  - [Prediction of severe cardiac complications with the help of myocardial perfusion
      scintigraphy in patients with residual chronic total occlusion after percutaneous
      coronary interventions].
AB  - Aim of the study was assessment of prognostic value of exercise myocardial
      perfusion scintigraphy in patients with stable and unstable angina in whom
      revascularization by percutaneous coronary intervention (PCI) was incomplete and
      at least one chronic total coronary artery occlusion (CTO) remained after PCI.
      Between March 2002 and December 2007 569 consecutive patients with multivessel
      lesions were subjected to SPECT imaging of myocardial perfusion after incomplete
      revascularization of the myocardium by PCI. At least 1 residual CTO was found in
      129 patients (79% men, mean age 64+/-8 years). Primary outcomes were defined as
      cardiac death or myocardial infarction. Secondary outcomes were registered in 10
      (7.9%) and 15 (11.9%) patients, respectively, with moderate and large transitory
      disturbances of perfusion. Logarithimic range criterion was statistically
      significant in patients distributed to groups by total estimation of rest in
      relation to cardiac complications. Univariate and multivariate Cox proportional
      hazards regression analysis gave additional important information for prediction
      of severe and nonsignificant cardiac complications when scintigraphic data were
      added to angiographic and clinical data, left ventricular ejection fraction, and
      results of treadmill test. Early monitoring with the use of myocardial
      scintigraphy by SPECT method is associated with increasing prognostic value
      relative to severe cardiac complications in patients subjected to incomplete
      revascularization by PCI, and having at least one residual chronic total
      occlusion.

PMID- 23548394
TI  - [Structure of cardiovascular pathology in pregnant women and efficacy of regional
      specialized management].
AB  - From 2000 to 2011 in prospective and retrospective studies we investigated
      pregnancy outcomes in all 30417 women treated within framework of the
      multidisciplinary management system for pregnant patients with cardiovascular
      diseases (hypertension, structural heart disease, aortic pathology and
      inflammatory autoimmune rheumatic diseases) designed and conducted in the Udmurt
      Republic of Russian Federation in late 1980-th. The system comprises specialized
      outpatient and inpatient departments, sanatorium and a maternity hospital at the
      regional cardiological center and provides ambulatory and hospital management and
      rehabilitation. Perinatal mortality decreased 65.8% from 11.1% in 2000 to 3.8% in
      2011. Within 20 years no mother died.

PMID- 23548395
TI  - [Methods of verification of bidirectional conduction block in cavotricuspid
      isthmus during treatment of typical atrial flutter].

PMID- 23548396
TI  - [A rational approach to the treatment of arterial hypertension in patients with
      high cardiovascular risk and metabolic disorders].
AB  - Metabolic disorders are important in the development of cardiovascular diseases.
      Experts predict their frequency is steadily rising, which is a serious medical
      and social problem in modern society. Arterial hypertension (AH) is the most
      common risk factor in patients with metabolic disorders. In the selection of
      antihypertensive therapy it is necessary to consider not only the anti
      hypertensive and organoprotective effects of drugs and their metabolic effects,
      which has prognostic value. Calcium antagonists, along with inhibitors of
      angiotensin converting enzyme (ACE) inhibitors and sartans have favorable
      metabolic effects. Lercanidipine related to the third generation dihydropyridine
      calcium antagonist, has been much more selective for the so-called slow calcium
      channels of vascular smooth muscle cells, which is associated with a good
      hypotensive, organo and metabolic action. Combination therapy with an ACE
      inhibitor and a calcium channel blocker, or angiotensin receptor blockers and
      calcium channel II is also a justified tactic for the management of patients with
      high-risk cardiovascular and metabolic disorders.

PMID- 23548397
TI  - [Adenosine triphosphate stress 99mTc-MIBI single-photon emission computed
      tomography in the diagnosis of ischemic heart disease].
AB  - This review is devoted to possibilities of single-photon emission computed
      tomography (SPECT) combined with pharmacological test with adenosine triphosphate
      (ATP) to detect myocardial ischemia in patients with ischemic heart disease
      (IHD). It contains consideration of contemporary problems and limitations
      inherent in use of pharmacological stress tests in radionuclide diagnostics;
      discussion of mechanisms of vasodilating effects of ATP in the context of modern
      concepts of purine receptors; detailed description of technique of
      pharmacological testing with ATP, as well as contraindications and possible side
      effects. Experience of foreign studies with the use of ATP stress testing for
      verification of presence of ischemia in patients with IHD is also presented.

PMID- 23548398
TI  - Archaeal community dynamics and abiotic characteristics in a mesophilic anaerobic
      co-digestion process treating fruit and vegetable processing waste sludge with
      chopped fresh artichoke waste.
AB  - This study evaluated the feasibility of obtaining methane in anaerobic digestion
      (AD) from the waste products generated by the processing of fruit and vegetables.
      During the first phase (0-55 d) of the AD using sludge from fruit and vegetable
      processing, an average value of 244+/-88 L kg(-1) dry matter d(-1)of biogas
      production was obtained, and methane content reached 65% of the biogas. Co
      digestion with chopped fresh artichoke wastes in a second phase (55-71 d)
      enhanced biogas production, and resulted in an average value of 354+/-68 L kg(-1)
      dry matter d(-1), with higher methane content (more than 70%). The archaeal
      community involved in methane production was studied using the ANAEROCHIP
      microarray and real-time PCR. Results indicated that species of Methanosaeta and
      Methanosarcina were important during the AD process. Methanosarcina numbers
      increased after the addition of chopped fresh artichoke, while Methanosaeta
      numbers decreased.

PMID- 23548399
TI  - Two-step in situ biodiesel production from microalgae with high free fatty acid
      content.
AB  - The yield of fatty acid methyl ester (FAME) from microalgae biomass is generally
      low via traditional extraction-conversion route due to the deficient solvent
      extraction. In this study a two-step in situ process was investigated to obtain a
      high FAME yield from microalgae biomass that had high free fatty acids (FFA)
      content. This was accomplished with a pre-esterification process using
      heterogeneous catalyst to reduce FFA content prior to the base-catalyzed
      transesterification. The two-step in situ process resulted in a total FAME
      recovery up to 94.87+/-0.86%, which was much higher than that obtained by a one
      step acid or base catalytic in situ process. The heterogeneous catalyst,
      Amberlyst-15, could be used for 8 cycles without significant loss in activity.
      This process have the potential to reduce the production cost of microalgae
      derived FAME and be more environmental compatible due to the higher FAME yield
      with reduced catalyst consumption.

PMID- 23548400
TI  - Bioleaching of rare earth and radioactive elements from red mud using Penicillium
      tricolor RM-10.
AB  - The aim of this work is to investigate biological leaching of rare earth elements
      (REEs) and radioactive elements from red mud, and to evaluate the radioactivity
      of the bioleached red mud used for construction materials. A filamentous, acid
      producing fungi named RM-10, identified as Penicillium tricolor, is isolated from
      red mud. In our bioleaching experiments by using RM-10, a total concentration of
      2% (w/v) red mud under one-step bioleaching process was generally found to give
      the maximum leaching ratios of the REEs and radioactive elements. However, the
      highest extraction yields are achieved under two-step bioleaching process at 10%
      (w/v) pulp density. At pulp densities of 2% and 5% (w/v), red mud processed under
      both one- and two-step bioleaching can meet the radioactivity regulations in
      China.

PMID- 23548401
TI  - Biodiesel production from hydrolysate of Cyperus esculentus waste by Chlorella
      vulgaris.
AB  - To reduce the cost of algal-based biodiesel, a waste material from oil industry,
      Cyperus esculentus waste, was used as the carbon source of the oleaginous
      microalgae Chlorella vulgaris. It demonstrated that C. vulgaris grew better in C.
      esculentus waste hydrolysate (CEWH(1)) than in glucose medium under the same
      reducing sugar concentration. CEWH concentration influenced the cell growth and
      lipid production significantly. The maximum lipid productivity 438.85 mg l(-1) d(
      1) was achieved at 40 g l(-1). Fed-batch culture was performed to further enhance
      lipid production. The maximum biomass, lipid content and lipid productivity were
      20.75 g l(-1), 36.52%, and 621.53 mg l(-1) d(-1), respectively. The produced
      biodiesel was analyzed by GC-MS and the results suggested that lipids produced
      from CEWH could be a potential feedstock for biodiesel production.

PMID- 23548402
TI  - Demonstrations of clinical initiatives to improve palliative care in the
      emergency department: a report from the IPAL-EM Initiative.
AB  - STUDY OBJECTIVE: We describe 11 clinical demonstrations of emergency department
      (ED) and palliative care integration to include traditional consultation services
      with hospital-based palliative care consultants through advanced integration
      demonstrations in which the ED provides subspecialty palliative care practice.
      METHODS: An interview guide was developed by the Improving Palliative Care in
      Emergency Medicine board that consists of emergency clinicians and palliative
      care practitioners. Structured interviews of 11 program leaders were conducted to
      describe the following key elements of the ED-palliative care integration, to
      include structure, function, and process of the programs, as well as strengths,
      areas of improvement, and any tools or outcome measures developed. RESULTS: In
      this limited number of programs, a variety of strategies are used to integrate
      palliative care in the ED, from traditional consultation to well-defined
      partnerships that include board-certified emergency clinicians in hospice and
      palliative medicine. CONCLUSION: A variety of methods to integrate palliative
      care in the emergency setting have emerged. Few programs collect outcomes-based
      metrics, and there is a lack of standardization about what metrics are tracked
      when tracking occurs.

PMID- 23548403
TI  - When do clinical decision rules improve patient care?

PMID- 23548404
TI  - The effect of computerized provider order entry systems on clinical care and work
      processes in emergency departments: a systematic review of the quantitative
      literature.
AB  - STUDY OBJECTIVE: We undertake a systematic review of the quantitative literature
      related to the effect of computerized provider order entry systems in the
      emergency department (ED). METHODS: We searched MEDLINE, EMBASE, Inspec, CINAHL,
      and CPOE.org for English-language studies published between January 1990 and May
      2011. RESULTS: We identified 1,063 articles, of which 22 met our inclusion
      criteria. Sixteen used a pre/post design; 2 were randomized controlled trials.
      Twelve studies reported outcomes related to patient flow/clinical work, 7
      examined decision support systems, and 6 reported effects on patient safety.
      There were no studies that measured decision support systems and its effect on
      patient flow/clinical work. Computerized provider order entry was associated with
      an increase in time spent on computers (up to 16.2% for nurses and 11.3% for
      physicians), with no significant change in time spent on patient care.
      Computerized provider order entry with decision support systems was related to
      significant decreases in prescribing errors (ranging from 17 to 201 errors per
      100 orders), potential adverse drug events (0.9 per 100 orders), and prescribing
      of excessive dosages (31% decrease for a targeted set of renal disease
      medications). CONCLUSION: There are tangible benefits associated with
      computerized provider order entry/decision support systems in the ED environment.
      Nevertheless, when considered as part of a framework of technical, clinical, and
      organizational components of the ED, the evidence base is neither consistent nor
      comprehensive. Multimethod research approaches (including qualitative research)
      can contribute to understanding of the multiple dimensions of ED care delivery,
      not as separate entities but as essential components of a highly integrated
      system of care.

PMID- 23548405
TI  - Automated detection using natural language processing of radiologists
      recommendations for additional imaging of incidental findings.
AB  - STUDY OBJECTIVE: As use of radiology studies increases, there is a concurrent
      increase in incidental findings (eg, lung nodules) for which the radiologist
      issues recommendations for additional imaging for follow-up. Busy emergency
      physicians may be challenged to carefully communicate recommendations for
      additional imaging not relevant to the patient's primary evaluation. The
      emergence of electronic health records and natural language processing algorithms
      may help address this quality gap. We seek to describe recommendations for
      additional imaging from our institution and develop and validate an automated
      natural language processing algorithm to reliably identify recommendations for
      additional imaging. METHODS: We developed a natural language processing algorithm
      to detect recommendations for additional imaging, using 3 iterative cycles of
      training and validation. The third cycle used 3,235 radiology reports (1,600 for
      algorithm training and 1,635 for validation) of discharged emergency department
      (ED) patients from which we determined the incidence of discharge-relevant
      recommendations for additional imaging and the frequency of appropriate discharge
      documentation. The test characteristics of the 3 natural language processing
      algorithm iterations were compared, using blinded chart review as the criterion
      standard. RESULTS: Discharge-relevant recommendations for additional imaging were
      found in 4.5% (95% confidence interval [CI] 3.5% to 5.5%) of ED radiology
      reports, but 51% (95% CI 43% to 59%) of discharge instructions failed to note
      those findings. The final natural language processing algorithm had 89% (95% CI
      82% to 94%) sensitivity and 98% (95% CI 97% to 98%) specificity for detecting
      recommendations for additional imaging. For discharge-relevant recommendations
      for additional imaging, sensitivity improved to 97% (95% CI 89% to 100%).
      CONCLUSION: Recommendations for additional imaging are common, and failure to
      document relevant recommendations for additional imaging in ED discharge
      instructions occurs frequently. The natural language processing algorithm's
      performance improved with each iteration and offers a promising error-prevention
      tool.

PMID- 23548406
TI  - The use of intracavernous injection and audiovisual sexual stimulation during
      real-time pharmacopenile doppler ultrasonography in vasculogenic erectile
      dysfunction.
AB  - INTRODUCTION: The objective of this study was to explore the role of
      intracavernous injection (ICI) and audiovisual sexual stimulation (AVSS) during
      real-time pharmacopenile Doppler ultrasonography (PDDU) in vasculogenic subtypes
      of erectile dysfunction. MATERIALS AND METHODS: A total of 200 consecutive men
      with erectile dysfunction (ED) were enrolled. Each patient received 2 sessions of
      real-time PDDU. Session A was performed under ICI alone. Session B was performed
      under ICI plus AVSS. The interval between sessions was 7 days. Penile vascular
      parameters, including peak systolic velocity (PSV), end diastolic velocity (EDV)
      and resistive index, were monitored 5, 10 and 20 min after the start of the test.
      Patients were asked to describe the level of sexual arousal generated by choosing
      one of the pre-set answers. RESULTS: In veno-occlusive ED, during session A, EDV
      at 10 min was significantly greater than at 5 and 20 min (p < 0.05). During
      session B, there was a significant difference regarding PSV in arteriogenic ED (p
      < 0.05). Mixed vasculogenic ED showed significant differences in PSV levels
      during session B, and EDV at 5 min was greater than at 10 and 20 min (p < 0.05).
      PDDU under ICI alone diagnosed 34 (17%), 35 (17.5%), 31 (15.5%) and 100 (50%)
      cases of arteriogenic, veno-occlusive, mixed vasculogenic and nonvasculogenic ED,
      respectively. The combination of ICI plus AVSS diagnosed 27 (13.5%), 44 (22%), 7
      (3.5%) and 122 (60.7%) cases, respectively. CONCLUSIONS: Adding AVSS during PDDU
      improves the recording of physiologic erectile response and may help the
      physician to accurately evaluate the cause of ED.

PMID- 23548407
TI  - Enhanced osteogenic fate and function of MC3T3-E1 cells on nanoengineered
      polystyrene surfaces with nanopillar and nanopore arrays.
AB  - During in vitro culture, cell fate and function, including cell adhesion,
      morphology, proliferation and differentiation, are affected by surface
      characteristics, such as geometry, wettability, hardness, chemistry and charge.
      This study replicated two different types of nanoengineered polystyrene surfaces
      (NPS) containing nanopillar (NPS-Pi) or nanopore (NPS-Po) arrays by hot embossing
      and investigated their topographical effects on cell behavior using osteoblast
      like MC3T3-E1 cells. To mass-replicate NPS, rigid metal nano-stamps were
      manufactured by nickel electroforming onto two different nano-templates: (1) a
      nanopore-arrayed anodic aluminum oxide nano-template using two-step
      electrochemical oxidation and (2) a nanopillar-arrayed polymer using hot
      embossing process. The physical and mechanical properties of the NPS, including
      geometry, wettability, hardness and elastic modulus, were evaluated with the help
      of field emission-scanning electron microscopy, a contact angle meter, and a
      nanoindenter. The nanotopography maintained the bulk property, while drastically
      changing the surface properties. In vitro the NPS had significant effects on
      MC3T3-E1 cell morphology, attachment, proliferation and osteogenic
      differentiation compared to a flat substrate due to the altered physical and
      mechanical surface properties of the nanoengineered surface. Interestingly, the
      NPS-Po was more effective at enhancing cell proliferation and osteogenesis
      differentiation. One potential explanation for these results may be that the
      subcellular binding sites induced by the nanostructures changed the cell
      morphology and promoted contractile cytoskeletons, thereby enhancing osteogenic
      differentiation. This, which allows for the cost-effective replication of NPS and
      the control of cell behavior, has various applications with respect to biomedical
      and cell surface interaction studies, in addition to enhanced osteogenic cell
      fate and function.

PMID- 23548409
TI  - Perspectives for the Comprehensive Headache-Specific Quality of Life
      Questionnaire (CHQQ). A response to the Editorial 'Assessing the quality of
      health-related quality of life measures' by Lipton et al.

PMID- 23548410
TI  - The malnutrition-inflammation-depression-arteriosclerosis complex is associated
      with an increased risk of cardiovascular disease and all-cause death in chronic
      hemodialysis patients.
AB  - BACKGROUND: In chronic hemodialysis patients, malnutrition, inflammation,
      depression and arteriosclerosis are pathogenetically associated suggesting the
      presence of malnutrition-inflammation-depression-arteriosclerosis (MIDA) complex
      acting as a risk factor for cardiovascular disease (CVD). METHODS: Nutritional
      status was assessed by serum albumin, subjective global assessment and normalized
      protein catabolic rate (nPCR). Inflammation was assessed by serum high
      sensitivity C-reactive protein (hsCRP). Depression was assessed with the Beck
      Depression Inventory and DSM-IV criteria. The severity of arteriosclerosis was
      measured by pulse wave velocity (PWV). RESULTS: Among 81 hemodialysis patients,
      44 (54.3%) had malnutrition (albumin <4.0 mg/dl with subjective global assessment
      score <6 and/or nPCR <1.0) and 39 (48.1%) had inflammation (hsCRP >1 mg/l). The
      prevalence of depression was 50.6% (n = 41). Fifty-nine (73.8%) had
      arteriosclerosis (measured PWV > expected PWV based on age/blood pressure/gender
      adjustment). The severity of the all four individual MIDA components correlated
      well with each other. The average number of the MIDA complication (MIDA score)
      was 2.27 +/- 1.33. -During the 5-year follow-up, 40 cases of CVD and 26 cases of
      all-cause death occurred. In Cox analysis adjusted for -previous CVD, age,
      diabetes, blood pressure, pulse pressure, intradialytic hypotension, B-type
      natriuretic peptide, -hemoglobin and hemodialysis incompliance, the MIDA score
      was an independent predictor of CVD and all-cause death: hazard ratio (95%
      confidence interval); 1.89 (1.13-3.17) and 3.48 (1.32-9.21) for an increase of 1
      MIDA score. CONCLUSIONS: This study suggests the presence of MIDA complex, which
      is composed of malnutrition, inflammation, depression and arteriosclerosis. The
      MIDA complex syndrome was an independent risk factor for CVD and all-cause death
      in chronic hemodialysis patients.

PMID- 23548411
TI  - Renin-angiotensin system blockers may create more risk than reward for sodium
      depleted cardiovascular patients with high plasma renin levels.
AB  - BACKGROUND: Four recent reports revealed differences in survival rates among
      treated cardiovascular patients taking renin-angiotensin system-blocking drugs.
      Patients with higher on-treatment plasma renin activity (PRA) levels died sooner
      of cardiovascular mortality than those with lower levels. We investigated whether
      excessive sodium depletion might have induced the higher PRA levels and
      contributed to the greater morbidity and mortality. METHODS: Using published
      data, ranges of PRA, blood pressures, drug usage, and biochemical parameters were
      compared among various groups of cardiovascular patients. RESULTS: We showed (i)
      that PRA levels are usually medium to low in treated cardiovascular patients, but
      are sometimes abnormally high, (ii) that excessive sodium depletion can induce
      such high PRA levels, (iii) that the higher PRA patients exhibited evidence of
      sodium depletion: lower blood pressures, more frequent natriuretic drug usage,
      lower N-terminal pro b-type natriuretic peptide (NT-proBNP), and higher blood
      urea nitrogen and uric acid levels, with similar usage of renin-angiotensin
      blocking drugs. CONCLUSIONS: We hypothesize that patients with high on-treatment
      PRA levels die sooner of cardiovascular events because they are excessively
      sodium-volume depleted. Moreover, renin-angiotensin system-blocking drugs may be
      harmful in such patients because they can functionally interfere with the effects
      of reactive rises in PRA that are triggered to prevent potentially dangerous
      falls in blood pressure, increases in plasma potassium, and falls in glomerular
      filtration rate. Careful liberalization of salt intake and subtraction of
      natriuretic drugs, sufficient to reduce reactive hyperreninemia without inducing
      unacceptable increases in blood pressure, might benefit such patients and
      decrease risk of adverse effects from drugs that block the renin-angiotensin
      system.

PMID- 23548412
TI  - Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the
      biogenic amine level of the adult rat brain: could oxytocin-induced labor cause
      pervasive developmental diseases?
AB  - Perinatal single-hormone treatment causes hormonal imprinting with lifelong
      consequences in receptor-binding capacity, hormone production as well as in
      social and sexual behavior. In the present experiments, newborn rats were treated
      with a single dose of oxytocin, and the levels of biogenic amines and their
      metabolites were studied in 8 different brain regions and in the sera when the
      male and female animals were 4 months old. Both dopaminergic and serotonergic
      neurotransmission was found to be significantly influenced. The levels of 3,4
      dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole acetic acid
      metabolites decreased in the hypothalamus and striatum. Dopamine, serotonin,
      norepinephrine, and 5-hydroxytryptophol levels were hardly altered, and there was
      no difference in the epinephrine levels. The results show that dopamine and
      serotonin metabolism of hypothalamus and striatum are deeply and lifelong
      influenced by a single neonatal oxytocin treatment Oxytocin imprinting resulted
      in decreased dopamine turnover in the hypothalamus and decreased serotonin
      turnover in the hypothalamus, medulla oblongata, and striatum of females. As the
      disturbance of brain dopamine and serotonin system has an important role in the
      development of pervasive developmental diseases (eg, autism) and neuropsychiatric
      disorders (eg, schizophrenia), the growing number of oxytocin-induced labor as a
      causal factor, cannot be omitted. 

PMID- 23548414
TI  - Smoking status modifies the relation between CYP1A1*2C gene polymorphism and
      idiopathic male infertility: the importance of gene-environment interaction
      analysis for genetic studies of the disease.
AB  - The study was designed to investigate the associations of polymorphisms Ile462Val
      and 3801T>C of the cytochrome P450 1A1 (CYP1A1) gene with idiopathic male
      infertility (IMI) and to assess the impact of smoking status on the relationship
      between the polymorphisms and the susceptibility to the disease. DNA samples from
      203 patients with IMI and 227 fertile men were genotyped for the polymorphisms by
      a polymerase chain reaction and restriction fragment length polymorphism methods.
      We found for the first time that the increased risk of IMI in carriers of
      genotype 462Ile/Val of the CYP1A1 gene occurred only in smoker men (odds ratio
      [OR] = 1.91; 95% confidence interval [CI] 1.01-3.59), whereas nonsmoker men did
      not have the risk of infertility (OR = 1.58; 95% CI 0.66-3.76). The results of
      our study demonstrate that the analysis of gene-environment interactions is
      necessary to explain conflicting results of genetic studies of IMI and to improve
      our understanding of the mechanisms of the disease. 

PMID- 23548415
TI  - Smoking cessation and desire to stop smoking in nine countries of the former
      Soviet Union.
AB  - INTRODUCTION: Smoking rates and corresponding levels of premature mortality from
      smoking-related diseases in the former Soviet Union (fSU) are among the highest
      in the world. To reduce this health burden, greater focus on smoking cessation is
      needed, but little is currently known about rates and characteristics of
      cessation in the fSU. METHODS: Nationally representative household survey data
      from a cross-sectional study of 18,000 respondents in Armenia, Azerbaijan,
      Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine were
      analyzed to describe patterns of desire and action taken to stop smoking, quit
      ratios (former ever-smokers as a percent of ever-smokers, without a specified
      recall period), and help used to stop smoking. Multivariate logistic regression
      was used to analyze characteristics associated with smoking cessation and desire
      to stop smoking. RESULTS: Quit ratios varied from 10.5% in Azerbaijan to 37.6% in
      Belarus. About 67.2% of respondents expressed a desire to quit, and 64.9% had
      taken action and tried to stop. The use of help to quit was extremely low
      (12.6%). Characteristics associated with cessation included being female, over
      60, with higher education, poorer health, lower alcohol dependency, higher
      knowledge of tobacco's health effects, and support for tobacco control.
      Characteristics associated with desire to stop smoking among current smokers
      included younger age, poorer health, greater knowledge of tobacco's health
      effects, and support for tobacco control. CONCLUSIONS: Quit ratios are low in the
      fSU but there is widespread desire to stop smoking. Stronger tobacco control and
      cessation support are urgently required to reduce smoking prevalence and
      associated premature mortality.

PMID- 23548413
TI  - Paternal fenvalerate exposure influences reproductive functions in the offspring.
AB  - Fenvalerate (Fen), a synthetic pyrethroid insecticide, has been shown to have
      adverse effects on male reproductive system. Thus, the aim of the present study
      was to elucidate whether these adverse effects are passed from exposed male mice
      to their offspring. Adult male mice received Fen (10 mg/kg) daily for 30 days and
      mated with untreated females to produce offspring. Fenvalerate significantly
      changed the methylation status of angiotensin I-converting enzyme (Ace), forkhead
      box O3 (Foxo3a), huntingtin-associated protein 1 (Hap1), nuclear receptor
      subfamily 3 (Nr3c2), promyelocytic leukemia (Pml), and Prostaglandin F2 receptor
      negative regulator (Ptgfrn) genes in paternal mice sperm genomic DNA. Further,
      Fen significantly increased sperm abnormalities; serum testosterone and estradiol
      17beta level in adult male (F0) and their male offspring (F1). Further, paternal
      Fen treatment significantly increased the length of estrous cycle, serum
      estradiol-17beta concentration in estrus, and progesterone levels in diestrus in
      female offspring (F1). These findings suggest that adverse effects of paternal
      Fen exposure on reproductive functions can be seen not only in treated males (F0)
      but also in their offsprings. 

PMID- 23548416
TI  - Silencing of HEPN1 is responsible for the aggressive biological behavior of
      pituitary somatotroph adenomas.
AB  - BACKGROUND/AIMS: The pathogenic mechanisms underlying pituitary adenoma
      formation, progression, and invasion are poorly understood. To identify candidate
      tumor suppressor genes, we selected somatotroph adenomas as representative of
      pituitary adenomas. METHODS/RESULTS: We used genome-wide differential expression
      analysis in 15 invasive and 12 noninvasive somatotroph adenomas. HEPN1 reduction
      was more frequent in the invasive group, and this result was confirmed by qRT
      PCR. To understand the function of HEPN1, the pituitary adenoma cell lines, GH3
      and GT1.1, were stably transfected with short hairpin RNA (shRNA) targeting HEPN1
      or ectogenic HEPN1 by lentivirus-mediated transfection. We found that HEPN1
      overexpression in GH3 and GT1.1 cells inhibited cell proliferation, induced
      apoptosis, and attenuated invasive capacity, whereas HEPN1 silencing enhanced
      cell proliferation and invasion accompanied by decreased apoptosis. Western blot
      analysis revealed that HEPN1 overexpression decreased MMP-2, MMP-9, and Bcl-2
      expression, but increased BAX, p53, and caspase-3 expression. In contrast, HEPN1
      silencing increased MMP-2, MMP-9, and Bcl-2 expression, but decreased BAX, p53,
      and caspase-3 expression. CONCLUSION: Taken together, our results suggest that
      reduction of HEPN1 may play an important role in the progression of pituitary
      somatotroph adenomas. HEPN1 may thus be a candidate as a prognostic predictor or
      an anticancer therapeutic target for patients with somatotroph adenoma.

PMID- 23548417
TI  - Temporal and optic pathway pilomyxoid astrocytoma mimicking dural-based lesion:
      case report and review of the literature.
AB  - Pilomyxoid astrocytomas (PMAs) are low-grade tumors that share many common traits
      with pilocytic astrocytomas. However, PMAs have a more worrisome clinical course,
      with a higher recurrence rate, lower survival rate, and higher risk of
      leptomeningeal spread compared to pilocytic tumors. These tumors tend to occur in
      younger children and are typically located in the area of the optic chiasm or
      hypothalamus. There are few studies examining the radiographic appearance of
      these lesions. In this case report, the authors present an unusual radiographic
      appearance of a PMA in an 11-year-old child. Preoperative images suggested a
      dural-based, homogenously enhancing lesion coupled with an enlarged optic nerve.
      Surgery revealed an intraparenchymal lesion of the right temporal lobe. There was
      hyperintensity on T2 MRI sequences, suggesting infiltration of the tumor along
      the optic tracts.

PMID- 23548418
TI  - Telomere length and expression of human telomerase reverse transcriptase splice
      variants in chronic lymphocytic leukemia.
AB  - Telomerase activity and telomere length (TL) are prognostic markers in chronic
      lymphocytic leukemia (CLL). The rate-limiting component of telomerase is human
      telomerase reverse transcriptase (hTERT), for which multiple transcripts exist.
      Two splicing sites, alpha and beta, have been described that generate deleted
      transcripts. Only the full-length (FL; alpha+beta+) transcript translates into a
      functional protein. The aim of this work was to characterize hTERT splice
      variants in CLL in relation to disease activity, clinical stage, immunoglobulin
      heavy chain variable (IGHV) genes mutational status, and TL. Real-time polymerase
      chain reaction assays were validated for quantification of the hTERT transcripts
      with either alpha deletion (del-alpha; alpha-beta+)), beta deletion (del-beta;
      alpha+beta-) or both alpha and beta deletions (del-alphabeta; alpha-beta-). The
      splice variant expression pattern was studied in 97 patients with CLL, 6 healthy
      control subjects, and one CD34 cell sample. TL was assessed with real-time
      polymerase chain reaction in 71 of 97 samples. Thirty-two percent of the cases
      did not express any of the splice variants. Average FL expression was 5.5-fold
      higher in IGHV-unmutated (n = 35) compared with mutated (n = 59) patients (p <
      0.0001). FL levels correlated directly with the percentage of IGHV homology (r =
      0.34; p = 0.0007) and inversely with TL (r = -0.44; p = 0.0001). Overall, FL
      expression correlated significantly with that of the other splice variants. All
      transcripts were more frequently expressed in progressive compared with
      nonprogressive patients (p < 0.0001 for FL and del-alpha; p = 0.01 for del-beta;
      and p = 0.006 for del-alphabeta). This study provides a detailed insight into the
      hTERT transcript pattern in CLL, highlighting the necessity of subgrouping
      patients according to IGHV mutation status when analyzing hTERT expression.

PMID- 23548419
TI  - Renal inflammatory changes in acute hepatic failure-associated acute kidney
      injury.
AB  - BACKGROUND/AIMS: Acute kidney injury (AKI) is a common complication in advanced
      liver dysfunction. Our aim is to clarify the mechanisms of acute hepatic failure
      (AHF)-associated AKI. METHODS: We examined the mechanisms of AHF-associated AKI,
      which is characterized by AKI in AHF and hyperbilirubinemia, following DA-to
      Lewis rat liver transplantation. RESULTS: During the progression of AHF and
      hyperbilirubinemia in liver graft rejection, AHF-associated AKI gradually
      developed by day 11. Degeneration and apoptotic cells were apparent in tubular
      epithelial cells with bile pigment accumulation and mitochondrial degeneration.
      Injury of peritubular capillaries (PTCs) was also noted with apoptotic
      endothelial cells, decreased expression of endothelial nitric oxide synthase,
      accumulation of alpha-smooth muscle actin+ pericytes and/or myofibroblasts, and
      inflammation. Angiogenic factors including vascular endothelial growth factor,
      angiopoietin-1, and angiopoietin-2 in the cortex were decreased on day 11. In
      addition, a marked reduction in the velocity of red blood cells in PTCs was
      evident in vivo. CONCLUSIONS: AHF-associated AKI seems to be mediated by renal
      tubular epithelial cell injury with bile pigment accumulation, impaired
      microcirculation caused by PTC endothelial cell injury with depletion of
      endothelial nitric oxide synthase and angiogenic factors, and by a decrease in
      RBC velocity and renal inflammation. Multiple mechanisms including tubular and
      PTC injuries and renal inflammation may be involved in the development of AHF
      associated AKI.

PMID- 23548420
TI  - [First experience of the study "Intramyocardial Multiple Precision Administration
      of Mononuclear Bone Marrow Cells in the Treatment of Myocardial Ischemia"].
AB  - Study aim - to elucidate possibilities of the use of precision administration of
      mononuclear bone marrow cells (MBMC) for the treatment of myocardial ischemia and
      heart failure. "Intramyocardial Multiple Precision Administration of Mononuclear
      Bone Marrow Cells in the Treatment of Myocardial Ischemia" was a double blind
      randomized placebo controlled study in which we included patients more or equal 6
      months after Q-wave myocardial infarction with systolic myocardial dysfunction
      (ejection fraction <35%), not requiring myocardial revascularization, receiving
      stable optimal medical therapy for more or equal 8 weeks, and with implanted
      cardioverter-defibrillator. Transplantation of MBMC was guided by fluoroscopy and
      tridimensional NOGA XP Cardiac Navigation System. For assessment of efficacy of
      the method we used surrogate end points: decrease of number of fixed perfusion
      defects according to SPECT data and improvement of regional myocardial
      contractility according to data of echocardiography. Results of dynamic
      observation of the first experience of MBMC administration are presented in this
      paper.

PMID- 23548421
TI  - [Pharmacogenomic control of angiotensin converting enzyme gene I/D polymorphism
      predominant risk factor of development of chronic heart failure and target of
      enalapril treatment].
AB  - Aim of investigation - to study effect of angiotensin-converting enzyme (ACE)
      gene polymorphism as a dominant risk factor of development of chronic heart
      failure (CHF) and target for effective therapy with ACE inhibitor enalapril in
      patients with ischemic heart disease. We followed 226 patients with CHF on stable
      permanent basic therapy comprising -adrenoblocker, diuretic, aldosterone
      antagonist, digoxin, and ACE inhibitor. Seventy eight patients received enalapril
      (starting dose 2.5 mg twice daily with subsequent titration up to 10-20 mg twice
      daily). Control group comprised 136 patients without cardiovascular
      abnormalities. Allele D of polymorphic locus I/D of ACE gene in homozygous state
      was associated with high risk of development and severity of clinical
      manifestations of CHF. In patients with D/D genotype of ACE gene at the
      background of therapy with enelapril we noted more pronounced lowering of CHF
      functional class and augmentation of left ventricular ejection fraction compared
      with patients having I/I and I/D genotypes. We revealed associative
      interrelationships of ACE gene polymorphism (polymorphic locus I/D) with
      development and severity of CHF as well as effectiveness of therapy with an ACE
      inhibitor enalapril.

PMID- 23548422
TI  - [State of the structure and functions of the arterial wall in patients with
      chronic heart failure against the background of permanent atrial fibrillation and
      assessment of vasoprotective effect of omega-3 polyunsaturated fatty acids].
AB  - PURPOSE: to evaluate the state of the structure and function of the arterial wall
      in patients with chronic heart failure (CHF) of ischemic etiology in combination
      with persistent atrial fibrillation (AF) AF and the dynamics of their changes
      during therapy with omega-3 polyunsaturated fatty acids (omega-3 PUFA). MATERIAL
      AND METHODS: in the first phase in order to identify characteristics of a CCF and
      the restructuring of the arterial wall 120 patients with coronary artery disease
      and chronic heart failure II-III functional class (FC) were included in the
      study, then were divided into two equal groups according to the presence of
      persistent AF. In the second phase patients with CHF and persistent AF were
      randomized into 2 groups of 30 people to determine the vasoprotective effect of
      omega-3 fatty acids compared with the standard treatment of CHF. The duration of
      treatment was 6 months. To assess the conductive and damping functions of
      arteries comprehensive sfigmopletizmografiyu was carried out. To assess the state
      of the arteries collagen matrix we determined the level of tissue inhibitor of
      matrix metalloproteinases type I (TIMP-1) by enzyme immunoassay. RESULTS: in
      patients with chronic heart failure of ischemic etiology in combination with
      persistent AF we revealed more severe functional impairment of the arterial wall,
      characterized by an increase in pulse wave velocity in carotid-femoral segment
      (p=0.037), the aorta (p<0.001), indexes CAVI1 (p less or equal 0.001) and
      augmentation (p=0.049; p<0.001) in the absence of differences in the group of
      patients with heart failure and sinus rhythm in terms of structural changes in
      collagen matrix- TIMP-1. The progress of CHF against the background persistent AF
      was characterized by higher levels of atrial natriuretic peptide with prevalence
      of diastolic dysfunction, while the more frequent co-morbidities (hypertension,
      diabetes mellitus type 2, stroke/transient ischemic attack), and risk factors.
      Inclusion in the treatment of patients with chronic heart failure of ischemic
      etiology and persistent AF omega-3 fatty acids provides reliable vasoprotective
      effect by suppressing the abnormal collagen formation on the dynamics of TIMP-1
      (p<0.001) and improving the elastic properties of the arterial wall to the
      dynamics of high-speed data and indexed blood flow the arterial tree (p<0.001),
      with the exception of ankle-brachial indexes. CONCLUSION: structurally functional
      remodeling of the arterial wall in patients with chronic heart failure of
      ischemic etiology and persistent AF has a definite pattern of forming. Omega-3
      fatty acids have a vasoprotective effect, providing improving elastic properties
      of the arteries by preventing fibrosis.

PMID- 23548423
TI  - [Effect of von Willebrand factor and endothelin-1 on formation of thrombotic
      status in patients with ischemic heart disease].
AB  - In 44 patients with ischemic heart disease (IHD) and 35 healthy subjects we
      studied cascade mechanism of platelets activation by von Willebrand factor (vWF),
      and interrelationship of platelet aggregation, level of vWF, and endothelial
      dysfunction. The latter was estimated by severity of vasoconstriction determined
      basing on endothelin-1 levels. Quantitative assessment of platelet aggregation
      revealed differences in aggregation capacity between healthy subjects and
      patients with IHD. Of particular importance was absence of spontaneous
      aggregation in healthy subjects. It was shown that in IHD patients influence of
      vWF resulted in augmentation and convergence of activating signal. Positive
      correlation was found in patients with IHD between elevation of levels of vWF,
      endothelin-1, and spontaneous and induced platelet aggregation activity.
      Interrelationship was revealed between character of IHD course and degree of
      elevation of the studied markers.

PMID- 23548424
TI  - [Obstructive sleep apnea syndrome in patients with acute myocardial infarction:
      timing of onset of the disease, clinico-functional and some other
      characteristics].
AB  - With the aim of elucidating special features of the course of acute myocardial
      infarction (MI) in patients with obstructive sleep apnea syndrome (OSA) we
      retrospectively studied clinico-functional parameters of 476 patients including
      64 (13.3%) who had episodes of apnea during sleep. Frequency of OSA was 1.3 times
      greater in overweight patients, and 2.3 times greater in those with history of
      diabetes mellitus. Development of MIs in patients with OSA more often occurred
      during night or early morning (relative risk 6.00-7.41) and depended on the
      severity of OSA. Patients with MI and OSA had lowering of blood levels of high
      density lipoproteins, elevation of levels of triglycerides and high sensitive C
      reactive protein. We noted the role of excessive neurohumoral activity in these
      processes. A conclusion was made about necessity of timely diagnosis of OSA
      during MI and timely correction of the revealed pathophysiological traits.

PMID- 23548425
TI  - [The FORTISSIMO program: advantages of fixed full dose combination of perindopril
      arginine and indapamide in the treatment of poorly controlled arterial
      hypertension].
AB  - In the Russian program FORTISSIMO administration of fixed combination of
      perindopril arginine/indapamide (10 mg/2.5 mg) in 2120 patients with poorly
      controlled arterial hypertension instead of angiotensin converting enzyme
      inhibitors (ACEI) or -receptor antagonists (ARB) with hydrochlorothiazide given
      separately or in fixed combinations resulted in significant lowering of arterial
      pressure (AP) and achievement of its target level in 84% of patients. Mean AP was
      lowered from 177/99 to 130/80 mm Hg in 3 months while substantial reduction down
      to 149/89 mm Hg occurred just after 2 weeks of treatment. Improvement of
      compliance to therapy was also noted. Fixed perindopril/indapamide combination
      was well tolerated and turned out to be effective for AP control irrespective of
      previously conducted therapy (ACEI or ARB with diuretic).

PMID- 23548426
TI  - [Influence of antihypertensive therapy and other methods of secondary prevention
      on cognitive functions in patients with hypertension at high risk for
      complications].

PMID- 23548427
TI  - [Electrocardiographic predictors of response to cardiac resynchronization therapy
      of heart failure in patients with dilated cardiomyopathy].
AB  - The aim of our study was to identify electrocardiographic predictors of response
      to cardiac resynchronization therapy (CRT) in patients with dilated
      cardiomyopathy (DCM). METHODS: 46 patients with DCM (76% men; mean age 48.8+/-12
      years; mean NYHA class 3.09+/-0.3; mean QRS duration 167+/-30.1 ms; left
      ventricular ejection fraction 23.5+/-6%) had CRT implanted. Assessment of
      clinical, laboratory and echocardiographic (including TDI) and 12-lead surface
      ECG parameters was performed at baseline, in 24 hours post CRT implantation and
      after 6 months of follow-up. Multivariate logistic regression analysis selected
      the following independent predictors of response to CRT: two pre-implantation -
      baseline RS width in lead V1 >= 113.5 ms (OR 0.94, 95% CI 0.814-1.00; p=0.000),
      BNP <= 456 g/ml (OR 0.92, 95% CI 0.797-1.00; p=0.001); and two post-implantation:
      shortening of QRS width - DeltaQRS >= -24.5 ms (OR 0.80, 95% CI 0.586-1.00;
      p=0.01) and shortening of RS V1 width - DeltaRSV1 >= -21.8 ms (S: 0.87, 95% CI
      0.72-1.00; p= 0.002) in 24 hours after CRT.

PMID- 23548428
TI  - [Interrelationship between polymorphic markers of methylenetetrahydrofolate
      reductase gene and development of acute disturbance of brain circulation in
      families of patients with atrial fibrillation].
AB  - In the present work we for the first time on the clinic-genetic material revealed
      genetic predictors of development of acute disturbance of brain circulation
      (ADBC) in families of patients with atrial fibrillation (AF) namely polymorphism
      of the methylenetetrahydrofolate reductase (MTHFR) gene. Genotype CC was
      significantly more often found among patients with AF and ADBC compared with
      controls (58.1 and 35.2%, respectively, p=0.02) as well as in relatives of
      probands compared with the control group (59.3 and 35.2%, respectively, p=0.008).
      With this in relatives with revealed paroxysmal AF and ADBC we also noted
      presence of CC genotype. Taking into consideration the relationship obtained
      between polymorphysms of MTHFR gene and AF it was possible to assume that
      polymorphic marker CC appeared to be a predictor of ADBC in these families.

PMID- 23548429
TI  - [Clinical role of lipoprotein-associated phospholipase A2].
AB  - Inflammation plays an important role in origin and progression of atheromatous
      plaque. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered a
      biomarker of inflammation and a predictor of vascular events. Lp-PLA2 is an
      enzyme secreted by leukocytes and associated with circulating lipoproteins and
      macrophages in atherosclerotic plaques. Lp-PLA2 hydrolizes phospholipids of
      oxidized low density lipoproteins and generates two proinflammatory mediators,
      lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a
      major role in the development of atherosclerotic lesions, myocardial infarction
      and ischemic stroke. Recently the first publications appeared about selective
      inhibitor of phospholipase A2 - darapladib as a novel therapeutic approach for
      the treatment of patients with coronary artery disease. However, first results
      need to be confirmed by ongoing large long-term randomized clinical trials.

PMID- 23548430
TI  - [Mechanisms of development of thromboembolic complications in patients with
      atrial fibrillation].
AB  - Thomboembolism is the most threatening complication in patients with atrial
      fibrillation. Main source of embolism is the left atrial thrombosis. Mechanisms
      of development of thromboembolic complications in patients with arrhythmias are
      far from being deciphered. In this review we discuss possible mechanisms of
      formation of intracardiac thrombus - abnormalities of functioning of the
      hemostasis system, endothelial dysfunction, inflammatory reactions, fibrosis of
      the left atrial wall, genetic traits.

PMID- 23548431
TI  - [Cardiac resynchronizing therapy. Selection of patients and their management
      after implantation of biventricular heart pacemaker].
AB  - Chronic heart failure (CHF) - a widely spread manifestation of various forms of
      heart diseases - is characterized by high mortality. Prognosis is especially
      unfavorable in patients with wide QRS complex. Method of resynchronizing therapy
      was elaborated for the treatment of this group of patients in addition of medical
      therapy. Its efficacy for improvement of clinical course and prognosis of CHF was
      demonstrated in a number of randomized controlled trials. However according to
      some data in 30-45% of cases application of the method is associated with no
      clinical improvement or reversal of cardiac remodeling when standard criteria
      (left ventricular ejection fraction less or equal 35%, QRS 120-150 ms, functional
      class II-IV) are used for patients selection. In this review we consider
      possibilities of various methods of selection of patients providing maximal
      probability of efficacy. We also present analysis of techniques of detection of
      implantation site of left ventricular lead and various tactics of management of
      patients after implantation of biventricular pacemaker.

PMID- 23548432
TI  - [Angiotensin II receptor antagonists in cardiology: course to organoprotection].

PMID- 23548433
TI  - [Bleeding in the appointment of dabigatran in the patients with renal
      insufficiency caused by coadministration of spironolactone and ACE inhibitors].
AB  - It is a case report of bleeding when using dabigatran in patient with renal
      failure caused by the concurrent use of spironolactone and angiotensin-converting
      enzyme (ACE) inhibitors. The patient (75 years old) at the decompensation of
      chronic heart failure in the background of persistent atrial fibrillation was
      appointed the combination of ACE inhibitors, spironolactone, and dabigatran. 10
      days after the start of using spironolactone and dabigatran bleeding was marked
      with decrease in hemoglobin levels to 69 g/l, creatinine level increases to 3.6
      mg/dL (glomerular filtration rate by MDRD 18 ml/min/1,73 m2), and potassium to
      5.5 mEq/ l. Against the background of the abolition of drugs normalization of
      renal function was marked. The question of an increased risk of nephrotoxicity
      with concurrent use of ACE inhibitors and spironolactone is discussed.

PMID- 23548434
TI  - From language-specific to shared syntactic representations: the influence of
      second language proficiency on syntactic sharing in bilinguals.
AB  - Studies on cross-linguistic syntactic priming suggest that bilinguals can share
      syntactic representations across languages (e.g., Hartsuiker, Pickering, &
      Veltkamp, 2004). But how are these representations established in late learners
      of a second language? Specifically, are representations of syntactic structures
      in a second language (L2) immediately collapsed with similar structures of the
      first language (L1), or are they initially represented separately? In order to
      investigate this, we primed the use of English genitives with Dutch (Experiment
      1) and English (Experiment 2) genitives (e.g., het hemd van de jongen/the shirt
      of the boy vs. de jongen zijn hemd/the boy's shirt) in late Dutch-English
      bilinguals with varying levels of proficiency in English (their L2). The head
      nouns of prime and target constructions either had the same meaning (hemd/shirt -
      shirt) or a different meaning (duim/thumb - shirt), in order to test whether the
      use of both genitives was generalized across nouns. Experiment 1 found stronger
      between-language priming for more than less proficient bilinguals in both
      conditions, thus suggesting a shift from language-specific to shared syntactic
      representations. Experiment 2 suggests that these early, language-specific
      syntactic representations might be item-specific: Less proficient bilinguals
      showed much weaker priming when the heads of prime and target constructions had
      different meanings than when they were repeated.

PMID- 23548435
TI  - Preillumination of lettuce seedlings with red light enhances the resistance of
      photosynthetic apparatus to UV-A.
AB  - Seedlings of 10-day-old lettuce (Lactuca sativa L., cultivar Berlin) were
      preilluminated by low intensity red light (lambdamax=660 nm, 10 min, 5 MUmol
      quanta m(-2) s(-1)) and far-red light (lambdamax=730 nm, 10 min, 5 MUmol quanta
      m(-2) s(-1)) to study the effect of pre-treatment on photosynthesis,
      photochemical activity of photosystem II (PSII), the contents of photosynthetic
      and UV-A-absorbing pigments (UAPs) and H2O2, as well as total and ascorbate
      peroxidase activities in cotyledonary leaves of seedlings exposed to UV-A. UV
      radiation reduced the photosynthetic rate (Pn), the activity of PSII, and the
      contents of Chl a and b, carotenoids and UAPs in the leaves, but increased the
      content of H2O2 and the total peroxidase activity. Preillumination with red light
      removed these effects of UV. In turn, the illumination with red light, then far
      red light removed the effect of the red light. Illumination with red light alone
      increased the content of UAPs, as well as peroxidase activity. It is suggested
      that higher resistance of the lettuce photosynthetic apparatus to UV-A radiation
      is associated with involvement of the active form of phytochrome B, thereby
      increasing peroxidase activities as well as UAPs and saving preservation of
      photosynthetic pigment contents due to pre-illumination with red light.

PMID- 23548437
TI  - Abstracts of the 8th Annual International Congress of Complementary Medicine
      Research, ICCMR 2013. London, United Kingdom. April, 11-13, 2013.

PMID- 23548436
TI  - Heterogeneity of cell death.
AB  - Cell death constitutes a number of heterogeneous processes. Despite the dynamic
      nature of cell death, studies of cell death have primarily focused on apoptosis,
      and cell death has often been viewed as static events occurring in linear
      pathways. In this article we review cell death heterogeneity with specific focus
      on 4 aspects of cell death: the type of cell death; how it is induced; its
      mechanism(s); the results of cell death, and the implications of cell death
      heterogeneity for both basic and clinical research. This specifically reveals
      that cell death occurs in multiple overlapping forms that simultaneously occur
      within a population. Network and pathway heterogeneity in cell death is also
      discussed. Failure to integrate cell death heterogeneity within analyses can lead
      to inaccurate predictions of the amount of cell death that takes place in a
      tumor. Similarly, many molecular methods employed in cell death studies
      homogenize a population removing heterogeneity between individual cells and can
      be deceiving. Finally, and most importantly, cell death heterogeneity is linked
      to the formation of new genome systems through induction of aneuploidy and genome
      chaos (rapid genome reorganization).

PMID- 23548438
TI  - The usefulness of job relocation and serum eosinophil cationic protein in baker's
      asthma.
AB  - BACKGROUND: Although the most widely recommended treatment for occupational
      asthma is to completely avoid the causative agents, job relocation within the
      same company is often substituted for a complete career change. However, there is
      not much data on the efficacy of job relocation within the workplace and
      appropriate follow-up parameters. We investigated baker's asthma patients to
      validate the efficacy of job relocation and follow-up markers. METHODS: Twelve
      bakery plant workers diagnosed with baker's asthma were enrolled in the study.
      Asthma-related symptoms and methacholine provocation test were followed up 6
      months after a job relocation. Skin prick test and ELISA to detect wheat flour
      specific IgE and eosinophil cationic protein (ECP) in sputum and serum were also
      followed up to evaluate the status of allergic inflammation. RESULTS: After a 6
      month job relocation, all 12 workers showed an improvement in symptoms, and
      airway hyperresponsiveness to methacholine was negatively converted in 9 of them.
      There were no significant differences in skin reactivity and serum flour-specific
      IgE levels before and after the relocation. While sputum ECP levels did not show
      a significant difference (338.3 +/- 93.0 MUg/l vs. 175.0 +/- 78.9 MUg/l, p =
      0.118), there was a remarkable difference in serum ECP levels before and after
      the relocation (12.2 +/- 3.0 MUg/l vs. 2.8 +/- 3.1 MUg/l, p = 0.004).
      CONCLUSIONS: Job relocation was effective in managing baker's asthma. Serum ECP
      level was a useful follow-up marker of baker's asthma.

PMID- 23548439
TI  - Rare fungal illness follows tornado.

PMID- 23548440
TI  - Mac1+/Gr1+ cells contribute to transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is a serious complication
      associated with blood transfusion and can cause transfusion associated
      fatalities. Both antibody dependent and non-dependent mechanisms are involved in
      TRALI, as proposed over the past years. Nonetheless, many details of the immune
      cells involved in TRALI, particularly the Mac1(+)/Gr1(+) cells from donors, are
      not fully understood yet. Here we used an in vitro transwell system and a mouse
      model to study the role of donor leukocytes, present in the donor material, in
      the occurrence of TRALI reactions. We found that there is a number of immature
      myeloid cells with Mac1(+)/Gr1(+) phenotype present in the red blood cell (RBC)
      products, when prepared by regular methods. We found that murine Mac1(+)/Gr1(+)
      cells from stored RBC products display an elevated MHC I and CD40 expression, as
      well as an enhanced tumor necrosis factor alpha(TNF-alpha), interlukin-6(IL-6)
      and macrophage inflammatory protein 2 (MIP-2) secretion. When tested in a
      transwell endothelial migration assay, Mac1(+)/Gr1(+) cells showed a significant
      capability to cross the endothelial barrier. In vivo investigation demonstrated
      that compared to the purified RBC transfusion, more murine Mac1(+)/Gr1(+) cells
      from the regular method produced RBC sequestered in the lung, which associated to
      shorter survival. Taken together, these data suggest that donor derived
      Mac1(+)/Gr1(+) cells can play a significant role in TRALI reactions, and that
      reduction of Mac1(+)/Gr1(+) cell number from RBC products is necessary to control
      the severity of TRALI reactions in clinic.

PMID- 23548441
TI  - Sniff nasal pressure is a sensitive marker of poor outcome in amyotrophic lateral
      sclerosis.

PMID- 23548442
TI  - Is there a disparity in the hospital care received under a universal health
      insurance program in Taiwan?
AB  - OBJECTIVE: To analyze the disparity in hospital care among people of various
      socio-economic status (SES) under a universal health insurance scheme. DESIGN: A
      survey questionnaire was mailed to discharged patients in October 2010. SETTING:
      This study included 183 large-scale hospitals in Taiwan. PARTICIPANTS: A total of
      3015 patients/caregivers completed the questionnaires, which yielded a response
      rate of 58%. MAIN OUTCOME MEASURES: Three variables were included. The two access
      to-care variables were admission route and accreditation level of the hospital in
      which the patient stayed. A structured questionnaire, the patient-reported
      hospital quality (PRHQ), was included to characterize patient's experience of
      hospital stay. RESULTS: Patients with lower education were less likely to be
      admitted to a hospital according to a planned schedule, or to choose an Medical
      Center Hospital. However, SES was not associated with the PRHQ scores.
      Furthermore, patients with unplanned admission were associated with lower PRHQ
      scores than those with planned admission to the hospital. CONCLUSIONS: Under the
      universal health insurance system in Taiwan, lower education is associated with
      unplanned admission to a hospital, which might result in poorer perceived quality
      of care. Reducing unplanned admission is a challenge for health authorities in
      the future.

PMID- 23548443
TI  - Classroom and simulation team training: a randomized controlled trial.
AB  - OBJECTIVE: To test the hypotheses that classroom and simulation-based crew
      resource management (CRM) training interventions improve teamwork attitudes and
      behaviours of participants and that classroom training combined with simulation
      based training provide synergistic improvements. DESIGN: A randomized controlled
      trial. SETTING: Area Health Service in New South Wales, Australia. PARTICIPANTS:
      A total of 157 doctors, nurses and midwives randomized into one of four groups,
      consisting of three intervention groups and a control group. INTERVENTION: One
      day CRM-based classroom course; one-day CRM style simulation-based training or
      classroom training followed by simulation-based training. MAIN OUTCOME MEASURES:
      Pre- and post-test quantitative participant teamwork attitudes, and post-test
      quantitative trainee reactions, knowledge and behaviour. RESULTS: Ninety-four
      doctors, nurses and midwives completed pre-intervention attitude questionnaires
      and 60 clinicians completed post-intervention assessments. No positive changes in
      teamwork attitudes were found associated with classroom or simulation training.
      Positive changes were found in knowledge (mean difference 1.50, 95% confidence
      interval (CI) 0.58-2.43, P = 0.002), self-assessed teamwork behaviour (mean
      difference 2.69, 95% CI 0.90-6.13, P = 0.009) and independently observed teamwork
      behaviour (mean difference 2.30, 95% CI 0.30-4.30, P = 0.027) when classroom-only
      trained group was compared with control; however, these changes were not found in
      the group that received classroom followed by simulation training. CONCLUSIONS:
      Classroom-based training alone resulted in improvements in participant knowledge
      and observed teamwork behaviour. The study found no additional impact of
      simulation training.

PMID- 23548444
TI  - Ankle replacement revision.

PMID- 23548446
TI  - The saphenous nerve in foot and ankle surgery: its variable anatomy and
      relevance.
AB  - BACKGROUND: Several studies have raised doubt regarding the role of the saphenous
      nerve (SN) in the foot, and some authors omit the SN from ankle blocks. Our aim
      was to assess the SN anatomy with reference to foot and ankle surgery. METHODS:
      In 29 cadaveric feet the SN was traced to its termination. At the ankle, the
      distances from the SN to the tibialis anterior tendon (TAT) and the long
      saphenous vein (LSV) were recorded. RESULTS: In 24 specimens, a SN was present at
      the ankle, and in 19 specimens extended to the foot. The mean distances from the
      nerve to the TAT and LSV were 15 mm and 4mm respectively. The nerve reached the
      first metatarsal (MT) in 28% of specimens. CONCLUSION: Although the SN anatomy is
      less extensive than previously described, it often reaches the first MT and
      therefore should routinely be included in ankle blocks for forefoot surgery.

PMID- 23548445
TI  - Biometry of the calcaneocuboid joint: biomechanical implications.
AB  - Precise biometric data of calcaneus, cuboid bones and calcaneocuboid joint are
      not alluded to in textbooks of anatomy. This study focussed on the biometry of 50
      calcanei, 30 cuboid dry bones, and anatomical specimens of 21 transverse tarsal
      joints. Measurement of the length, width, angular orientation, contact surface
      and radius of curvature, rolling band of the joints surfaces according to the
      main axes were performed. The results focussed on biometric variations with
      several morphological types never identified previously. Measurements obtained on
      dry bones and anatomical specimens with the functions of ligaments were
      distinguished. The morphology of the calcaneus could explain the results of
      osteotomy procedures for the treatment of adult flatfoot. A better knowledge of
      the joint surfaces and biometric data would generate a modeling of the
      calcaneocuboid joint and function in locking the transverse tarsal joint.

PMID- 23548447
TI  - The diagnostic value of single photon-emission computed tomography bone scans
      combined with CT (SPECT-CT) in diseases of the foot and ankle.
AB  - BACKGROUND: A radionuclide bone scan with single photon-emission computed
      tomography and CT (SPECT-CT) is a new imaging modality which combines highly
      detailed CT with the functional information from a triple phase radionuclide bone
      scan. Little has been published about its diagnostic accuracy and usefulness in
      foot and ankle pathology. The aim of this study is to evaluate whether bone scans
      with SPECT-CT provide a useful contribution to the management of patients with
      foot and ankle pain, and whether it results in changes to clinical management.
      METHODS: A retrospective study involving 50 patients was conducted between March
      2010 and April 2011. SPECT-CT was requested in cases where definitive clinical
      diagnosis could not be achieved after clinical examination and plain radiography.
      Pathology as highlighted on SPECT-CT was taken as the definitive diagnosis in
      these patients and was treated accordingly. Patients were subsequently seen in
      the follow up clinic to evaluate the outcome of their treatment. RESULTS: In 11
      patients (22%), the provisional clinical diagnosis matched with the findings of
      the SPECT-CT and no change in treatment was necessary. In 39 patients (78%) the
      findings of the SPECT-CT did not correlate exactly with the initial clinical
      diagnosis and led to a modified treatment plan. The accuracy, sensitivity,
      specificity, positive predictive and negative predictive value of SPECT-CT in
      this series was 94%, 95.45%, 83.3%, 97.6% and 71.43% respectively. CONCLUSIONS:
      SPECT-CT is a useful investigation tool in foot and ankle pathologies. The
      present study shows a high diagnostic accuracy and we recommend its use in cases
      with diagnostic uncertainty.

PMID- 23548448
TI  - Matrix-associated stem cell transplantation (MAST) in chondral defects of foot
      and ankle is effective.
AB  - BACKGROUND: The aim of the study was to assess the feasibility and clinical
      results of matrix-associated stem cell transplantation (MAST) and 2-year-follow
      up in chondral defects of foot and ankle. METHODS: In a prospective, consecutive,
      non-controlled clinical follow-up study, all patients with chondral defects, that
      were treated with MAST from April 1st to November 30th, 2009 were analyzed. The
      size and location of the chondral defects, method-associated problems and the
      Visual Analogue Scale Foot and Ankle (VAS FA) before treatment and at follow-up
      were registered and analyzed. RESULTS: Twenty-six chondral defects in 25 patients
      were included in the study. The mean age of the patients was 33 years (range, 16
      48 years), 18 (72%) were male. The VAS FA before surgery was 49.2 on average
      (range, 24.3-68.4). The defects were located as follows: medial talar shoulder,
      n=9; lateral talar shoulder, n=13 (medial and lateral talar shoulder, n=1);
      distal tibia, n=1; posterior calcaneal facet, n=1; head of 1st metatarsal, n=2.
      The defect size was 1.1cm(2) on average (range, .5-6 cm(2)). All patients
      completed 2-year-followup. No complications or consecutive surgeries were
      registered. The mean VAS FA at follow-up was 94.5 (range, 73.4-100; t-test,
      p<.01). CONCLUSIONS: MAST led to good clinical scores. No complications were
      registered. Even though a control group is missing, we conclude that MAST is a
      safe and effective method for the treatment of chondral defects. The main
      advantage of MAST in comparison with ACI and MACI is the single procedure
      methodology. The advantage in comparison with AMIC is the potential higher
      concentration of stem cells.

PMID- 23548449
TI  - Arthrorisis with calcaneostop screw in children corrects Talo-1st Metatarsal
      Index (TMT-Index).
AB  - BACKGROUND: Arthrorisis (other terms: Arthrorhisis or Arthroreisis) with
      calcaneostop screw is one option for the treatment of flatfoot (Pes
      abductoplanovalgus) in children. The aim of the study was to analyze the amount
      of correction (for example Talo-1st Metatarsal-Index (TMT-Index)) and clinical
      outcome including pedographic assessment. METHODS: In a prospective consecutive
      non-controlled clinical follow-up study, all patients that were treated with
      arthrorisis with calcaneostop screw from September 1st 2006 to August 31st, 2009
      were included. One foot was operated at a time, and the contralateral foot was
      operated 3 months later if indicated. Postoperatively, 15 kg partial weight
      bearing was performed for 6 weeks. The screws were removed after 2-year-followup.
      Assessment was performed before surgery, at two-year-followup, and at 2.5-year
      followup. The assessment staging of posterior tibialis insufficiency, radiographs
      with full weight bearing (TMT-Index), pedography, and Visual-Analogue-Scale Foot
      and Ankle (VAS FA). RESULTS: 18 patients/31 feet were included in the study (age,
      10.6 [8-12], 45% male). No complications were observed. In comparison with the
      preoperative parameters, the parameters posterior tibialis insufficiency stage,
      percentage of increased pedographic midfoot contact area and force were
      decreased, and TMT dorsoplantar/lateral/Index and VAS FA scores were increased at
      both followups (each p<.05). The parameters did not differ between followups
      (each p >=.4). CONCLUSIONS: All relevant parameters (stage of posterior tibialis
      insufficiency, TMT dorsoplantar/lateral/Index, pedographic midfoot contact area
      and force, VAS FA) improved after arthrorisis with calcaneostop screw (before and
      after screw removal) in pes abductoplanovalgus in children. Since the
      complication rate is very low, this method allows safe and predictable
      correction.

PMID- 23548450
TI  - Bipartite talus: a case series and algorithm for treatment.
AB  - BACKGROUND: Bipartite talus is a rare condition of uncertain aetiology, with
      various treatment options described. METHODS: We report five symptomatic
      bipartite talus cases in four male patients warranting surgical management. All
      patients were reviewed by an independent assessor. RESULTS: The youngest patient
      presented with bilateral lesions without sub-talar arthrosis. He was treated
      twice by internal fixation with bone grafting. The left side failed to unite. The
      second patient presented with isolated sub-talar osteoarthritis. He underwent
      fragment excision and sub-talar arthrodesis with bone graft. The third patient
      presented aged 55 with severe hind-foot osteoarthritis, and underwent tibio-talar
      calcaneal fusion. The final patient was treated with fragment excision and sub
      talar arthrodesis. All patients reported symptom improvement or resolution post
      operatively. Four cases showed evidence of radiographic union. CONCLUSIONS: We
      suggest a treatment rationale of fragment fusion if large enough, or excision if
      not, with associated limited fusion if the adjacent joints are markedly
      degenerate.

PMID- 23548451
TI  - Effect of different orthotic concepts as first line treatment of plantar
      fasciitis.
AB  - BACKGROUND: Evaluation of the effectiveness of three different types of
      prefabricated foot orthotics in the treatment of plantar fasciitis. METHODS:
      Prospective, randomized head-to-head trial in 30 adults (21 women, 9 men) with
      plantar fasciitis without any anatomic alterations. Three different prefabricated
      orthotics were tested (thin, non supportive orthotic (NO); soft supportive foam
      orthotic (FO); foam covered rigid self-supporting plastic orthotic (PO)). The
      follow up was 3 weeks. Main outcome measures were maximum and average pain (VAS),
      duration of pain per day, walking distance and subjective comfort. RESULTS: There
      was no significant effect of NO on maximal pain and average pain. FO and PO had a
      significant effect on pain levels (p<0.05) whereas PO was superior concerning
      pain reduction and the time until the onset of effect (p<0.05). CONCLUSIONS: PO
      are superior regarding pain reduction and pain free time when compared to FO. NO
      did not demonstrate a significant effect in the test setup used.

PMID- 23548452
TI  - A comparison of lateral ankle ligament suture anchor strength.
AB  - BACKGROUND: Lateral ankle ligament repairs increasingly use suture anchors
      instead of bone tunnels. Our purpose was to compare the biomechanical properties
      of a knotted and knotless suture anchor appropriate for a lateral ankle ligament
      reconstruction. METHODS: In porcine distal fibulae, 10 samples of 2 different
      PEEK anchors were inserted. The attached sutures were cyclically loaded between
      10N and 60N for 200 cycles. A destructive pull was performed and failure loads,
      cyclic displacement, stiffness, and failure mode recorded. RESULTS: PushLock 2.5
      anchors failed before 200 cycles. PushLock 100 cycle displacement was less than
      Morphix 2.5 displacement (p<0.001). Ultimate failure load for anchors completing
      200 cycles was 86.5N (PushLock) and 252.1N (Morphix) (p<0.05). The failure mode
      was suture breaking for all PushLocks while the Morphix failed equally by anchor
      breaking and suture breakage. CONCLUSIONS: The knotted Morphix demonstrated more
      displacement and greater failure strength than the knotless PushLock. The
      PushLock failed consistently with suture breaking. The Morphix anchor failed both
      by anchor breaking and by suture breaking.

PMID- 23548453
TI  - What is the best clinical test for Achilles tendinopathy?
AB  - BACKGROUND: Differential diagnosis of Achilles pathology is demanding. This study
      evaluates the diagnostic accuracy of clinical tests identified for a chronic mid
      body Achilles tendinopathy. Ultrasound scanning provides the reference standard.
      METHODS: Twenty-one participants with, and without, an Achilles tendinopathy, had
      an ultrasound scan followed immediately by the application of ten clinical tests.
      The accuracy and reproducibility of each test was determined. RESULTS: The most
      valid tests are; pain on palpation of the tendon (sensitivity 84%, specificity
      73%, kappa 0.74-0.96) and the subjective reporting of pain 2-6 cm above the
      insertion into the calcaneum (sensitivity 78%, specificity 77%, kappa 0.75-0.81).
      CONCLUSION: Only location of pain and pain on palpation were found to be
      sufficiently reliable and accurate, to be recommended for use.

PMID- 23548454
TI  - The effect of preoperative foot and ankle physiotherapy group on reducing
      inpatient stay and improving patient care.
AB  - BACKGROUND: Benefits of day case foot and ankle surgery include reduced hospital
      stay, cost savings, high patient satisfaction, quicker recovery with no increased
      complications. The preoperative foot and ankle group was set up in 2007 to reduce
      inpatient hospital stays and increase the rate of day case procedures. METHODS:
      We evaluated length of stay and physiotherapy intervention for all our patients
      during the first three months of 2007-2011. RESULTS: Median length of stay was
      statistically significant (p<0.05) in all groups apart from the ankle group. Day
      case surgery rates increased in all groups apart from hindfoot group but the
      result was only significant for forefoot and midfoot groups. CONCLUSION: The
      results show that the setting up our group has resulted in reduced inpatient
      stay, increase in day case surgery rates with significant cost savings.

PMID- 23548455
TI  - Effect of immobilization, off-loading and zoledronic acid on bone mineral density
      in patients with acute Charcot neuroarthropathy: a prospective randomized trial.
AB  - BACKGROUND: Bisphosphonates are commonly used as an adjuvant in the management of
      acute Charcot neuroarthropathy (CNA), although the clinical efficacy of the
      treatment is controversial. The aim of the present study is to investigate the
      effect of immobilization and zoledronic acid on bone mineral density (BMD)
      changes during the treatment of acute CNA. METHODS: Thirty-five patients with
      acute midfoot CNA were randomly assigned to treatment with either zolendronic
      acid or placebo. BMD of the lumbar spine and both hips was measured at baseline
      and after six months of treatment. RESULTS: Comparison between BMD at
      presentation and at 6 months demonstrated a significant fall in BMD in the
      placebo group at the CNA-affected femoral neck (-3.2%, p=0.016) and in the CNA
      free hip (-1.2%, p=0.026). Conversely, a significant rise in BMD was observed in
      the zolendronic acid group at all measured areas of the CNA-free hip. DISCUSSION
      AND CONCLUSIONS: Immobilization and off-loading does not lead to marked disuse
      osteoporosis in patients with acute CNA after 6 months of treatment. Treatment
      with zoledronic acid led to a statistically significant increase in hip BMD
      compared to placebo.

PMID- 23548456
TI  - Arthroscopic resection of talocalcaneal coalitions--a bicentre case series of a
      new technique.
AB  - BACKGROUND: Symptomatic tarsal coalitions failing conservative treatment are
      traditionally managed by open resection. We describe an arthroscopic technique
      for excising talocalcaneal coalitions and present a retrospective two-surgeon
      case series of the first eight patients (nine feet). METHODS: Outcome measures
      include restoration of subtalar movements, return to work and sports, visual
      analogue pain scales and Sports Athlete Foot and Ankle Scores (SAFAS). Follow-up
      ranges from 1 to 5.5 years. RESULTS: Pain and SAFAS improved in 7 patients.
      Subtalar movements were improved in all feet. All patients achieved early good
      function but one relapsed requiring subsequent fusions. One posterior tibial
      nerve was damaged. CONCLUSIONS: Minimal destruction of bone and soft tissues
      allows early mobilization and minimizes pain. Patient selection and preoperative
      planning are crucial to avoid relapse and complication. This series from two
      independent surgeons supports the feasibility and effectiveness of this
      technique.

PMID- 23548457
TI  - Severe scar problems following use of a locking barbed skin closure system in the
      foot.
AB  - BACKGROUND: Barbed sutures provide a novel technique for knotless wound closure.
      They have mainly been used in plastic and general surgery. There are no reports
      about its use in the foot. METHODS: We present a case series of 11 feet in 8
      patients whose wounds were closed with barbed sutures. Ten had primary hallux
      valgus correction and one had a revision correction. RESULTS: No problems were
      noted at 2-weeks follow-up. Four of the 11 cases required open suture excision
      due to an adverse reaction. Five were followed to delayed wound healing.
      Histology results from one scar showed a localised histiocytic reaction and
      superficial dermal abscess formation. CONCLUSIONS: We feel the thin subcutaneous
      tissue of the foot, the amount of motion and pressure from the shoe causes the
      barbs to repeatedly irritate the soft tissue. Based on our short case series we
      cannot recommend the use of a barbed skin closure system in the foot.

PMID- 23548458
TI  - Nils Silfverskiold (1888-1957) and gastrocnemius contracture.
AB  - Nils Silfverskiold was an orthopaedic surgeon, Swedish aristocrat, bon vivant,
      Olympic gymnast, left wing intellectual and anti-Nazi who described that the
      force required to dorsiflex the ankle in spastic equinus contracture decreased
      with knee flexion in isolated gastrocnemius contracture. He advocated detaching
      the origins of the gastrocnemii from the femur and reattaching them to the tibia.
      The Silfverskiold knee flexion test has now also been adapted to distinguish
      between isolated gastrocnemius contracture and combined shortening of the
      gastrocnemius-soleus complex in non-spastic contracture by measuring the range of
      ankle dorsiflexion with the knee flexed and the knee straight.

PMID- 23548459
TI  - An oblique plantar incision aids deformity correction in surgical treatment of
      paediatric curly toes.

PMID- 23548460
TI  - Re: Anatomical reconstruction of the lateral ligaments using Gracillis tendon in
      chronic ankle instability; a new technique [Foot Ankle Surg 2011;17(4):239-46].

PMID- 23548461
TI  - Chronic sinus formation using non absorbable braided suture following open repair
      of Achilles tendon.
AB  - This study reports a case of a 34 year old man who sustained an Achilles tendon
      rupture which was surgically repaired using a non-absorbable suture that was
      complicated by a deep sinus and chronic infection. Despite antibiotics, surgical
      debridement and skin grafting, his condition did not resolve. Further imaging
      revealed a sinus leading to the core suture knot that was eccentrically placed
      but not buried within the healed tendon repair, and the offending suture was
      subsequently removed. This case highlights the importance of meticulous surgical
      technique when performing Achilles tendon repair and a high index of suspicion
      for early imaging when patients present with chronic wound infection post
      operatively. The authors urge surgeons to use routinely use an absorbable non
      braided suture, which remains buried within the core when performing Achilles
      tendon repair.

PMID- 23548462
TI  - Cervical intraspinal microstimulation evokes robust forelimb movements before and
      after injury.
AB  - OBJECTIVE: Intraspinal microstimulation (ISMS) is a promising method for
      reanimating paralyzed limbs following neurological injury. ISMS within the
      cervical and lumbar spinal cord is capable of evoking a variety of highly
      functional movements prior to injury, but the ability of ISMS to evoke forelimb
      movements after cervical spinal cord injury is unknown. Here we examine the
      forelimb movements and muscles activated by cervical ISMS both before and after
      contusion injury. APPROACH: We documented the forelimb muscles activated and
      movements evoked via systematic stimulation of the rodent cervical spinal cord
      both before injury and three, six and nine weeks following a moderate C4/C5
      lateralized contusion injury. Animals were anesthetized with isoflurane to permit
      construction of somatotopic maps of evoked movements and quantify evoked muscle
      synergies between cervical segments C3 and T1. MAIN RESULTS: When ISMS was
      delivered to the cervical spinal cord, a variety of responses were observed at
      68% of locations tested, with a spatial distribution that generally corresponded
      to the location of motor neuron pools. Stimulus currents required to achieve
      movement and the number of sites where movements could be evoked were unchanged
      by spinal cord injury. A transient shift toward extension-dominated movements and
      restricted muscle synergies were observed at three and six weeks following
      injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns
      were similar to spinally-intact animals. SIGNIFICANCE: The results demonstrate
      the potential for cervical ISMS to reanimate hand and arm function following
      spinal cord injury. Robust forelimb movements can be evoked both before and
      during the chronic stages of recovery from a clinically relevant and sustained
      cervical contusion injury.

PMID- 23548463
TI  - Atrichia with papular lesions in a chinese family caused by novel compound
      heterozygous mutations and literature review.
AB  - BACKGROUND: Congenital atrichia with papular lesions (APL) is characterized by
      complete absence of body hair shortly after birth, along with papules, and caused
      by mutations in the hairless gene (HR). OBJECTIVE: To investigate whether APL
      with HR mutations might also be found among patients in non-consanguineous
      Chinese families and to discuss the phenotypic variations with the same
      mutations. METHODS: DNA sequencing of the HR was performed in the Chinese
      pedigree and in 100 controls. RESULTS: A nonsense mutation c.T2265A in the
      patient and his father as well as a 2bp deletion (3482delCT) in the patient and
      his mother were detected. CONCLUSION: Our study identified the first mutation in
      exon 10 in HR as well as the second novel compound heterozygous mutations in a
      Chinese family, also adding new variants to the knowledge of HR mutations in APL.
      Phenotypic heterogeneity in congenital atrichia might be subject to the founder
      genes or modifier genes.

PMID- 23548464
TI  - Prognostic significance of pretreatment 18F-FDG PET/CT in patients with
      relapsed/refractory B-cell non-Hodgkin's lymphoma treated by radioimmunotherapy
      using 131I-rituximab.
AB  - AIMS: It was the aim of this paper to identify prognostic factors in patients
      with relapsed or refractory B-cell non-Hodgkin's lymphomas, treated by
      radioimmunotherapy (RIT) with radioiodinated human/murine chimeric anti-CD20
      monoclonal antibody rituximab (131I-rituximab). METHODS: Twenty-four patients
      were enrolled prospectively and were treated with unlabeled rituximab 70 mg and a
      therapeutic activity (median 7.3 GBq) of 131I-rituximab. Contrast-enhanced 18F
      FDG PET/CT scans were performed before and after 1 month of RIT. Tumor sizes and
      maximum standardized uptake values (SUVmax) of scans were measured. RESULTS: Four
      of the 24 patients survived. High SUVmax in a pretreatment scan was found to be
      related to poorer overall survival (OS) and progression-free survival (p = 0.04
      and 0.02, respectively). Furthermore, a large tumor size in a pretreatment scan
      was associated with poorer OS but not with progression-free survival (p < 0.01
      and p = 0.07, respectively). By multivariate analyses, a high SUVmax, a large
      tumor size in a pretreatment scan and diffuse large B-cell lymphoma histology
      were significantly associated with poorer OS [p = 0.04/hazard ratio (HR) = 3.54,
      p < 0.01/HR = 5.52, and p = 0.02/HR = 3.38, respectively). CONCLUSION: SUVmax and
      tumor size determined by a pretreatment 18F-FDG PET/CT result as significant
      predictors of OS in patients with relapsed or refractory B-cell non-Hodgkin's
      lymphoma treated by RIT.

PMID- 23548465
TI  - Dalteparin dosing in high-flux haemodialysis and haemodiafiltration.
AB  - BACKGROUND: Low-molecular-weight heparins are being increasingly used as an
      alternative to unfractionated heparin for anticoagulation of the haemodialysis
      (HD) circuit. Data on dalteparin use in high-flux HD and haemodiafiltration (HDF)
      are limited. We examined the safety and efficacy of dalteparin in this setting to
      enable recommendations on the optimal dose range. METHODS: This prospective study
      was conducted in a single dialysis unit. Subjects who had been receiving
      dalteparin for at least 10 HD sessions were studied. Anti-Xa activity was
      measured for all subjects at the start of the HD session, at 60 min into HD and
      at the end of dialysis. RESULTS: 55 subjects were studied. None had detectable
      anti-Xa activity at the start of the session. Using adequacy criteria based on
      target anti-Xa activity >0.4 IU/ml at 1 h and <0.4 IU/ml at the end of dialysis,
      39 (71%) patients had adequate anticoagulation, 12 (22%) patients were under
      anticoagulated and 4 (7%) were over-anticoagulated. The mean dose in the
      adequately anticoagulated group was 60.7 +/- 11.7 IU/kg, in the under
      anticoagulated group 39.3 +/- 9.6 IU/kg and in the over-anticoagulated group 70.1
      +/- 14.6 IU/kg. The optimal dose of dalteparin appears to be 60 +/- 10 IU/kg,
      which facilitates the achievement of the target anti-Xa activity in the range of
      0.4-0.75 IU/ml at 1 h and <0.4 IU/ml at the session end. CONCLUSION: Dalteparin
      is a safe and effective anticoagulant for patients on high-flux HD and HDF. The
      optimal dose appears to be 60 +/- 10 IU/kg. The desirable target range of anti-Xa
      activity is 0.4-0.75 at 1 h and <0.4 IU/ml at the session end.

PMID- 23548466
TI  - Ultrasonography imaging during nasal endoscopic transsphenoidal surgery.
AB  - A 59-year-old Japanese woman presented with right visual impairment and tunnel
      vision. Pituitary gland tumor was diagnosed and nasal endoscopic transsphenoidal
      surgery was performed. Following partial removal of the posterior wall of the
      sphenoid sinus and extension of the ultrasonography probe to contact the dura
      mater, the bilateral carotid arteries and the pituitary gland tumor were clearly
      visualized. The ultrasonography image became clearer when the sphenoid sinus was
      filled with physiological saline. Histopathological analysis of the resected
      specimen revealed a pituitary adenoma. Ultrasonography was particularly useful in
      depicting the arteries, showing the tumor at the nasal endoscopic transsphenoidal
      surgery.

PMID- 23548467
TI  - 'Remote FASH' tele-sonography - a novel tool to assist diagnosing HIV-associated
      extrapulmonary tuberculosis in remote areas.
AB  - Diagnosis of tuberculosis (TB) is complex, especially in HIV positive patients.
      Ultrasound can aid diagnosis of extrapulmonary TB (EPTB), but experienced
      sonographers are often not available in endemic settings. We describe a novel
      tool to aid diagnosis of EPTB using telemedicine and a previously described
      standardized protocol for fast assessment with sonography of HIV/TB patients
      (FASH).

PMID- 23548468
TI  - Oral challenges with four apple cultivars result in significant differences in
      oral allergy symptoms.
AB  - BACKGROUND: We analyzed the hypoallergenic potential of a recently bred apple
      selection with unusually low content of Mal d 1, using an oral challenge model
      with three additional apple cultivars for comparison. METHODS: Sixty-six birch
      pollen-allergic individuals with a history of oral allergy syndrome after apple
      intake were subjected to a double-blind oral provocation with two apple cultivars
      (B:0654 and 'Discovery'). Thirteen also tested two other apple cultivars ('Ingrid
      Marie' and 'Gloster'). Three doses were given consecutively, 30 min apart: 10 g
      without peel, and 10 and 50 g with peel. A final assessment was conducted 30 min
      after the last intake. Oral symptoms were graded from 0 to 5. Total oral symptom
      score (TOS) included all scores for each cultivar at all time points. RESULTS:
      B:0654 induced significantly higher TOS than 'Discovery' when tested by 66
      individuals, in spite of its lower Mal d 1 content. TOS values were higher in
      females and increased with increasing age of the individuals when challenged with
      'Discovery'. Among the 13 individuals who tested all four cultivars, B:0654
      produced a higher score after the second dose compared to 'Ingrid Marie'. This
      was also the case after the third dose compared to 'Ingrid Marie' and 'Gloster',
      and again 30 min after the last intake compared to each of the other three
      cultivars, as well as a higher TOS compared to each of the other three cultivars
      (all p < 0.01). CONCLUSIONS: Our test was safe and well tolerated, and produced
      significant differences among the apple cultivars. Contrary to expectations,
      B:0654 was less well tolerated than the other three cultivars.

PMID- 23548469
TI  - Evaluating real-world use of cinacalcet and biochemical response to therapy in US
      hemodialysis patients.
AB  - BACKGROUND/AIMS: Data describing real-world use and effectiveness of cinacalcet
      are limited. We aimed to characterize predictors of treatment and changes in
      secondary hyperparathyroidism (SHPT) biochemistry after cinacalcet initiation.
      METHODS: We studied 25,250 in-center hemodialysis patients from a large dialysis
      provider, alive through November 2004, with no prior cinacalcet prescription.
      Patients were followed until initiation of cinacalcet, censoring, death, or July
      31, 2007. Initiators were further followed for dose titration and
      discontinuation. Predictors of these events were evaluated using Cox proportional
      hazards modeling. Biochemical parameters and other SHPT medication use were
      compared between baseline, pre-initiation, and post-initiation time points.
      RESULTS: Over an average of 1.25 years of follow-up, 30% of patients initiated
      cinacalcet therapy. Between baseline and initiation (mean of 386 days),
      parathyroid hormone (PTH) and phosphorus levels increased 78 and 7%,
      respectively, in these patients. After adjustment, cinacalcet initiation was
      associated with higher SHPT severity, younger age, African-American race, higher
      phosphorus levels, and more comorbidity. Within 1 month of initiation, median PTH
      was reduced by 15-30% and phosphorus by 3-5%. Reductions were sustained or
      increased over 12 months, depending on initiating PTH level and whether dose up
      titration occurred. Discontinuation was common, although many patients
      reinitiated. CONCLUSIONS: A substantial proportion of patients experienced SHPT
      progression and initiated cinacalcet treatment. Reductions in biochemistry varied
      by disease severity and whether doses were titrated.

PMID- 23548470
TI  - Estimating wastewater impacts from fracking.

PMID- 23548471
TI  - The UK Obstetric Surveillance System: impact on patient safety.
AB  - The UK Obstetric Surveillance System is a national system that allows for the
      collection of information on a range of rare disorders of pregnancy, enabling
      national descriptive, case-control and cohort studies. The population-based
      nature of the studies conducted renders them less susceptible to the biases
      typically associated with observational studies. Data collected using The UK
      Obstetric Surveillance System and similar systems can be used to address a range
      of patient safety issues. These include assessing the safety of different
      treatment options, using the data as an aid to service planning, as part of
      ongoing quality-improvement initiatives, as a benchmark against which to compare
      hospital-level disease incidence and outcomes, to inform and audit national
      guidelines, and to monitor the effect of changes in practice or policy. Studies
      can be introduced rapidly in response to newly arising safety concerns.
      International comparisons can further enhance the utility of these data for
      improving patient safety. 

PMID- 23548472
TI  - Characterization of spatiotemporal changes for the classification of dynamic
      contrast-enhanced magnetic-resonance breast lesions.
AB  - OBJECTIVE: The early detection of breast cancer is one of the most important
      predictors in determining the prognosis for women with malignant tumours. Dynamic
      contrast-enhanced magnetic-resonance imaging (DCE-MRI) is an important imaging
      modality for detecting and interpreting the different breast lesions from a time
      sequence of images and has proved to be a very sensitive modality for breast
      cancer diagnosis. However, DCE-MRI exhibits only a moderate specificity, thus
      leading to a high rate of false positives, resulting in unnecessary biopsies that
      are stressful and physically painful for the patient and lead to an increase in
      the cost of treatment. There is a strong medical need for a DCE-MRI computer
      aided diagnosis tool that would offer a reliable support to the physician's
      decision providing a high level of sensitivity and specificity. METHODS: In our
      study we investigated the possibility of increasing differentiation between the
      malignant and the benign lesions with respect to the spatial variation of the
      temporal enhancements of three parametric maps, i.e., the initial enhancement
      (IE) map, the post-initial enhancement (PIE) map and the signal enhancement ratio
      (SER) map, by introducing additional methods along with the grey-level co
      occurrence matrix, i.e., a second-order statistical method already applied for
      quantifying the spatiotemporal variations. We introduced the grey-level run
      length matrix and the grey-level difference matrix, representing two additional,
      second-order statistical methods, and the circular Gabor as a frequency-domain
      based method. Each of the additional methods is for the first time applied to the
      DCE-MRI data to differentiate between the malignant and the benign breast
      lesions. We applied the least-square minimum-distance classifier (LSMD), logistic
      regression and least-squares support vector machine (LS-SVM) classifiers on a
      total of 115 (78 malignant and 37 benign) breast DCE-MRI cases. The performances
      were evaluated using ten experiments of a ten-fold cross-validation. RESULTS: Our
      experimental analysis revealed the PIE map, together with the feature subset in
      which the discriminating ability of the co-occurrence features was increased by
      adding the newly introduced features, to be the most significant for
      differentiation between the malignant and the benign lesions. That diagnostic
      test - the aforementioned combination of parametric map and the feature subset
      achieved the sensitivity of 0.9193 which is statistically significantly higher
      compared to other diagnostic tests after ten-experiments of a ten-fold cross
      validation and gave a statistically significantly higher specificity of 0.7819
      for the fixed 95% sensitivity after the receiver operating characteristic (ROC)
      curve analysis. Combining the information from all the three parametric maps
      significantly increased the area under the ROC curve (AUC) of the aforementioned
      diagnostic test for the LSMD and logistic regression; however, not for the LS
      SVM. The LSMD classifier yielded the highest area under the ROC curve when using
      the combined information, increasing the AUC from 0.9651 to 0.9755. CONCLUSION:
      Introducing new features to those of the grey-level co-occurrence matrix
      significantly increased the differentiation between the malignant and the benign
      breast lesions, thus resulting in a high sensitivity and improved specificity.

PMID- 23548473
TI  - Intra-abdominal umbilical vein varix associated with fetal cardiac failure: a
      pitfall to the prenatal diagnosis of alpha-zero-thalassemia.
AB  - Hydrops fetalis related to homozygous alpha-thalassemia is a rare condition in
      Western Europe. We report a case of fetal cardiac failure that occurred after a
      second-trimester diagnosis of fetal umbilical vein aneurysm that was postnatally
      related to alpha-thalassemia. 

PMID- 23548474
TI  - Fission product activity ratios measured at trace level over France during the
      Fukushima accident.
AB  - The nuclear accident of Fukushima Dai-ichi (Japan) which occurred after the
      tsunami that impacted the northeast coasts of Japan on March 11th, 2011 led to
      significant releases of radionuclides into the atmosphere and resulted in the
      detection of those radionuclides at a global scale. In order to track airborne
      radionuclides from the damaged reactors and to survey their potential impact on
      the French territory, the French Institute of Radiation Protection and Nuclear
      Safety (Institut de Radioprotection et de Surete Nucleaire IRSN) set up an
      enhanced surveillance system to give quick results as needed and later give
      quality trace level measurements. Radionuclides usually measured at trace levels
      such as (137)Cs and in a very sporadic way (131)I were reported. Radionuclides
      that we had never measured in air since the Chernobyl accident: (134)Cs, (136)Cs,
      the mother/daughter pairs (129m)Te-(129)Te and (132)Te-(132)I, and (140)La (from
      the mother-daughter pair (140)Ba- (140)La) were also reported. Except the
      (131)I/(137)Cs ratio, activity concentration ratios were constant. These ratios
      could be used to help source term assessment, or as data for transfer studies
      realized after the passage of contaminated air masses, typically using the
      (134)Cs/(137)Cs ratio. 

PMID- 23548475
TI  - NUSIMEP-7: uranium isotope amount ratios in uranium particles.
AB  - The Institute for Reference Materials and Measurements (IRMM) has extensive
      experience in the development of isotopic reference materials and the
      organization of interlaboratory comparisons (ILC) for nuclear measurements in
      compliance with the respective international guidelines (ISO Guide 34:2009 and
      ISO/IEC 17043:2010). The IRMM Nuclear Signatures Interlaboratory Measurement
      Evaluation Program (NUSIMEP) is an external quality control program with the
      objective of providing materials for measurements of trace amounts of nuclear
      materials in environmental matrices. Measurements of the isotopic ratios of the
      elements uranium and plutonium in small amounts, typical of those found in
      environmental samples, are required for nuclear safeguards and security, for the
      control of environmental contamination and for the detection of nuclear
      proliferation. The measurement results of participants in NUSIMEP are evaluated
      according to international guidelines in comparison to independent external
      certified reference values with demonstrated metrological traceability and
      uncertainty. NUSIMEP-7 focused on measurements of uranium isotope amount ratios
      in uranium particles aiming to support European Safeguards Directorate General
      for Energy (DG ENER), the International Atomic Energy Agency's (IAEA) network of
      analytical laboratories for environmental sampling (NWAL) and laboratories in the
      field of particle analysis. Each participant was provided two certified test
      samples: one with single and one with double isotopic enrichment. These NUSIMEP
      test samples were prepared by controlled hydrolysis of certified uranium
      hexafluoride in a specially designed aerosol deposition chamber at IRMM.
      Laboratories participating in NUSIMEP-7 received the test samples of uranium
      particles on two graphite disks with undisclosed isotopic ratio values
      n((234)U)/n((238)U), n((235)U)/n((238)U) and n((236)U)/n((238)U). The uranium
      isotope ratios had to be measured using their routine analytical procedures.
      Measurement of the major ratio n((235)U)/n((238)U) was obligatory; measurement of
      the minor ratios n((234)U)/n((238)U) and n((236)U)/n((238)U) was optional. Of the
      twenty-four institutes that registered for NUSIMEP-7, 17 have reported their
      results achieved by different analytical methods. The results of NUSIMEP-7
      confirm the capability of laboratories in measuring n((234)U)/n((238)U),
      n((235)U)/n((238)U) and n((236)U)/n((238)U) in uranium particles of the size
      below 1 MUm diameter. Furthermore, they underpin the recent advances in
      instrumental techniques in the field of particle analysis. In addition, feedback
      from the measurement communities from nuclear safeguards, nuclear security and
      earth sciences was collected in view of identifying future needs for NUSIMEP
      interlaboratory comparisons.

PMID- 23548476
TI  - Authors' reply.

PMID- 23548477
TI  - Vascular abnormalities of the distal deep digital flexor tendon in 8 draught
      horses identified on histological examination.
AB  - The purpose of this study was to provide a detailed description of the vascular
      changes in the distal part of deep digital flexor tendon (DDFT). Eight isolated
      forelimbs were collected from 8 horses with DDF tendinopathy diagnosed post
      mortem by ultrasound and gross anatomopathological examination. The samples were
      fixed in 10% neutral buffered formalin, softened in 4% phenol and dehydrated with
      ethylic alcohol. Goldner's Trichrome staining method was used. The
      histopathological examination revealed vascular proliferation associated with
      structural disorders of blood vessels. Angiogenesis, fibroplasia and consecutive
      hypertrophy of the vascular wall with or without vascular occlusion were the most
      common findings. Other histopathological findings were: endothelial cell edema,
      progressive metaplasia from squamous to cubic cells, vascular wall hyalinization,
      endothelial cells apoptosis/necrosis and endothelial desquamation. These results
      demonstrated damage of the distal deep digital flexor tendon vasculature which
      may progressively alter the structural integrity of the tendon and contribute to
      degenerative lesions.

PMID- 23548478
TI  - The effects of bee pollen extracts on the broiler chicken's gastrointestinal
      microflora.
AB  - The aim of this study was to investigate the effects of bee pollen ethanolic
      extracts on the in vivo gastrointestinal tract microflora colonization of broiler
      chickens. A completely randomized experiment based on six treatments (different
      concentrations of bee pollen - 0, 5, 15, 25, 35 and 45 g kg(-1) diet) was used
      during 7 weeks. The highest count of faecal Enterococci was found in the
      experimental group with the addition of 15 g of pollen (8.85 +/- 0.87 log CFU g(
      1)) per 1 kg of feed mixture. The highest count of Lactobacilli was detected in
      the experimental group with 35 g of pollen per 1 kg of feed mixture and the
      highest number of the Enterobacteriaceae genera count was found in the control
      group (8.43 +/- 0.15 log CFU g(-1)). Moreover, the MALDI TOF MS Biotyper
      identified the following genera: Escherichia coli, Proteus mirabilis, Klebsiella
      oxytoca, as well as Lactobacillus acidophilus, L. crispatus, L. fermentum and L.
      salivarius from the Lactobacilli group and Enterococcus avium, E. casseliflavus,
      E. cecorum, E. faecalis, E. faecium, E. gallinarum, E. hirae and E. malodoratus
      from the Enterococci group. Additionally, the in vitro antimicrobial activities
      of pollen against five bacteria species isolated from gastrointestinal tracts of
      chickens were tested. The best antimicrobial effect of the pollen extract was
      detected against K. oxytoca.

PMID- 23548479
TI  - Bovine Staphylococcus aureus: diagnostic properties of specific media.
AB  - As accurate discrimination between Staphylococcus (S.) aureus and NSA (non-S.
      aureus staphylococci) involved in bovine mastitis is essential in terms of
      clinical prognosis and outcome, the aim of this study was to reevaluate the
      classical bacteriological procedures to identify these agents. Various media and
      the coagulase tube test were investigated using 116 strains of S. aureus and 115
      of NSA, all isolated from cows with spontaneous intramammary infections (IMI).
      Furthermore, 25 NSA reference strains were analyzed. The study demonstrated that
      a few media were appropriate for differentiating S. aureus from NSA, provided
      that the staphylococci were isolated from bovine IMI. Evaluation of hemolysis
      further revealed that double or incomplete hemolysis are specific for S. aureus
      and are, therefore, a decisive diagnostic criterion. For strains showing complete
      hemolysis, maximal discrimination between S. aureus and NSA was observed by
      subculturing them on CHROMagar Staph. aureus.

PMID- 23548480
TI  - Guggulsterone sensitizes glioblastoma cells to Sonic hedgehog inhibitor SANT-1
      induced apoptosis in a Ras/NFkappaB dependent manner.
AB  - Since Shh pathway effector, Gli1, is overexpressed in gliomas, we investigated
      the effect of novel Shh inhibitor SANT-1 on glioma cell viability. Though SANT-1
      failed to induce apoptosis, it reduced proliferation of glioma stem-like cells.
      Apart from canonical Shh cascade, Gli1 is also induced by non-canonical pathways
      including NFkappaB. Therefore, a combinatorial strategy with Ras/NFkappaB
      inhibitor, Guggulsterone, was employed to enhance effectiveness of SANT-1.
      Guggulsterone inhibited Ras and NFkappaB activity and sensitized cells to SANT-1
      induced apoptosis via intrinsic apoptotic mechanism. Inhibition of either Ras or
      NFkappaB activity was sufficient to sensitize cells to SANT-1. Guggulsterone
      induced ERK activation also contributed to Caspase-9 activation. Since SANT-1 and
      Guggulsterone differentially target stem-like and non-stem glioma cells
      respectively, this combination warrants investigation as an effective anti-glioma
      therapy. 

PMID- 23548481
TI  - SIRT1 and Connexin40 Mediate the normal shear stress-induced inhibition of the
      proliferation of endothelial cells co-cultured with vascular smooth muscle cells.
AB  - BACKGROUND: Shear stress imposed by blood flow directly impacts endothelial cells
      (ECs), which are simultaneously influenced by neighboring vascular smooth muscle
      cells (VSMCs). However, the mechanisms by which shear stress and VSMCs modulate
      EC proliferation remain to be elucidated. METHODS: ECs, cultured alone or co
      cultured with VSMCs, were subjected to a normal level of laminar shear stress
      (NSS) of 15 dyne/cm(2) or kept under static conditions by using a parallel-plate
      flow chamber system, respectively. RESULTS: BrdU incorporation assay and flow
      cytometry revealed that NSS inhibited EC proliferation with or without VSMCs.
      Western blot analysis demonstrated that NSS down-regulated the expression of
      Connexin40 (Cx40) in both ECs cultured alone and ECs co-cultured with VSMCs,
      accompanied by the increased expression of SIRT1. Moreover, salermide, an
      inhibitor of SIRT1, as well as SIRT1-specifc siRNA transfection inhibited the
      effect of NSS on EC proliferation and Cx40 expression. In contrast, resveratrol,
      a SIRT1 activator, induced an alteration in ECs similar to the application of
      NSS. CONCLUSION: NSS inhibits the proliferation of ECs via SIRT1 and Cx40 in the
      presence or absence of VSMCs. The data suggest that NSS plays a protective role
      in vascular homeostasis by maintaining EC proliferation at a normal level.

PMID- 23548482
TI  - Qualitative and quantitative measurement of the singing voice.
AB  - OBJECTIVE: The aim of the study was to clarify the mechanisms underlying the
      singing voice. PATIENTS AND METHODS: Forty-eight professional opera singers
      underwent flexible and rigid endoscopy, spectrographic analysis and perceptual
      evaluation. RESULTS: The data provided by voice analysis were not as clear and
      relevant to the aim of our study as those commonly obtained for speech
      evaluation. Laryngoscopy with rigid and flexible fiber optics and the singing
      power ratio (SPR) measurement provided more applicable data. Indeed, the former
      allowed us to assess laryngeal position, the glottic pattern and vocal tract
      modifications during the actual singing performance. The latter, already
      recommended by other authors as a reliable vocal emission index, also yielded
      more relevant information in comparison with the assessment of voice quality.
      Specifically, SPR provided data directly correlated to both the years of singing
      activity and the vocal category of each singer (the higher the singing pitch, the
      wider the vocal extension). More importantly, the data fully reflected the
      subjective assessment of each phoniatrician. CONCLUSIONS: We suggest that the SPR
      indices can be used as the electroacoustic equivalent of the subjective judgment
      of vocal focus.

PMID- 23548483
TI  - What does it mean to call chronic pain a brain disease?
AB  - Multiple investigators have recently asked whether neuroimaging has shown that
      chronic pain is a brain disease. We review the clinical implications of seeing
      chronic pain as a brain disease. Abnormalities noted on imaging of peripheral
      structures have previously misled the clinical care of patients with chronic
      pain. We also cannot assume that the changes associated with chronic pain on
      neuroimaging are causal. When considering the significance of neuroimaging
      results, it is important to remember that "disease" is a concept that arises out
      of clinical medicine, not laboratory science. Following Canguilhem, we believe
      that disease is best defined as a structural or functional change that causes
      disvalue to the whole organism. It is important to be cautious in our assertions
      about chronic pain as a brain disease because these may have negative effects on
      1) the therapeutic dialogue between clinicians and patients; 2) the social
      dialogue about reimbursement for pain treatments and disability due to pain; and
      3) the chronic pain research agenda. Considered scientifically, we may be looking
      for the cause of chronic pain through neuroimaging, but considered clinically, we
      are in fact often looking to validate pain complaints. We should not yield to the
      temptation to validate pain with the magnetic resonance imaging scanner
      (structural or functional). We should not see pain as caused by the brain alone.
      Pain is not felt by the brain, but by the person. PERSPECTIVE: Neuroimaging
      investigators have argued that brain imaging may demonstrate that chronic pain is
      a brain disease. We argue that "disease" is a clinical concept and that
      conceiving of chronic pain as a brain disease can have negative consequences for
      research and clinical care of patients with chronic pain.

PMID- 23548484
TI  - Pain measurement and brain activity: will neuroimages replace pain ratings?
AB  - Arguments made for the advantages of replacing pain ratings with brain-imaging
      data include assumptions that pain ratings are less reliable and objective and
      that brain image data would greatly benefit the measurement of treatment
      efficacy. None of these assumptions are supported by available evidence. Self
      report of pain is predictable and does not necessarily reflect unreliability or
      error. Because pain is defined as an experience, magnitudes of its dimensions can
      be estimated by well-established methods, including those used to validate brain
      imaging of pain. Brain imaging helps to study pain mechanisms and might be used
      as proxy measures of pain in persons unable to provide verbal reports. Yet
      eliminating pain ratings or replacing them with neuroimaging data is misguided
      because brain images only help explain pain if they are used in conjunction with
      self-report. There is no objective readout mechanism of pain (pain thermometer)
      that is unaffected by psychological factors. Benefits from including neuroimaging
      data might include increased understanding of underlying neural mechanisms of
      treatment efficacy, discovery of new treatment vectors, and support of
      conclusions derived from self-report. However, neither brain imaging nor self
      report data are privileged over the other. The assumption that treatment efficacy
      is hampered by self-report has not been shown; there is a plethora of treatment
      studies showing that self-report is sensitive to treatment. Dismissal of
      patients' self-reports (pain ratings) by brain-imaging data is potentially
      harmful. The aim of replacing self-report with brain-imaging data is misguided
      and has no scientific or philosophical foundation. PERSPECTIVE: Although brain
      imaging may offer considerable insight into the neural mechanisms of pain,
      including relevant causes and correlations, brain images cannot and should not
      replace self-report. Only the latter assesses the experience of pain, which is
      not identical to neural activity. Brain imaging may help to explain pain, but
      replacing self-report with brain-imaging data would be philosophically and
      scientifically misguided and potentially harmful to pain patients.

PMID- 23548485
TI  - Central neuroimaging of pain.

PMID- 23548486
TI  - Is chronic pain a disease? Evaluating pain and nociception through self-report
      and neuroimaging.

PMID- 23548487
TI  - Reply to commentary.

PMID- 23548488
TI  - Reply to commentaries.

PMID- 23548489
TI  - The infancy of infant pain research: the experimental origins of infant pain
      denial.
AB  - Skepticism toward infant pain characterized much of 20th century research and
      clinical practice, with infant surgery routinely conducted with minimal or no
      anesthesia into the 1980s. This paper offers a historical exploration of how this
      view became common by reviewing and analyzing the experimental infant pain
      research of the 19th and early 20th centuries that contributed to the development
      of infant pain denial. These experiments used pinprick and electric shock, and
      the results were generally interpreted as evidence of infants' underdeveloped
      pain perception, attributed to their lack of brain maturation. Even clear
      responses to noxious stimuli were often dismissed as reflex responding. Later
      these experimental findings were used by anesthesiologists to support the
      lessened use of anesthesia for infants. Based on the reviewed literature, this
      paper suggests that 4 interrelated causes contributed to the denial of infant
      pain: the Darwinian view of the child as a lower being, extreme experimental
      caution, the mechanistic behaviorist perspective, and an increasing emphasis on
      brain and nervous system development. Ultimately this history can be read as a
      caution to modern researchers to be aware of their own biases, the risks of null
      hypothesis testing, and a purely mechanistic view of infants. PERSPECTIVE: This
      article reviews the history of 19th and early 20th century infant pain research,
      tracing how the widely accepted belief that infants could not feel pain developed
      in the period prior to the growing acceptance of infant pain. Four interrelated
      causes are posited to help explain the tolerance of infant pain denial until
      recent times.

PMID- 23548490
TI  - Is there support for abuse-deterrent and tamper-resistant opioid formulations?

PMID- 23548491
TI  - Reply to commentary.

PMID- 23548492
TI  - Does opiate use in traumatically injured individuals worsen pain and
      psychological outcomes?
AB  - Opiate use for chronic pain is becoming increasingly controversial. There has
      been a shift away from supporting the use of opiates for treatment of chronic
      pain. In addition to lack of effectiveness, concerns for adverse clinical
      outcomes, addiction, and death have provided the impetus for this change. The
      purpose of this study was to investigate the percent of trauma patients still
      using opiates, their pain levels, and psychological outcomes 4 months posttrauma.
      This was a study to evaluate chronic pain at 4 months posttrauma in 101
      participants from a single level 1 trauma center. Eighty of the 101 participants
      developed chronic pain 4 months after their initial traumatic injury (79%). Of
      those who developed chronic pain, 27 (26%) were still using opiates. Those using
      narcotics at 4 months posttrauma had significantly more pain, life interference,
      depression, and anxiety. Posttraumatic stress disorder (PTSD) was not
      significantly influenced by narcotic use in this analysis. However, the mean
      associated with those using narcotics was higher and diagnostic for PTSD. Those
      taking opiates did not have significantly better relief from their pain using
      treatments or medications than those not using opiates (F = 8, P = .08). These
      findings bring into question the appropriate use of opiates for chronic pain and
      the possible exacerbating effects on pain and psychopathology in traumatically
      injured patients. PERSPECTIVE: This article identifies data that provide evidence
      that narcotic pain medication needs to be used carefully in traumatically injured
      patients with chronic pain, especially in those individuals with comorbid
      psychological pathology.

PMID- 23548493
TI  - Right ventricular performance in preterm and term neonates: reference values of
      the tricuspid annular peak systolic velocity measured by tissue Doppler imaging.
AB  - BACKGROUND: The tricuspid annular peak systolic velocity (S') is an
      echocardiographic measurement to assess systolic right ventricular function in
      adults and children. OBJECTIVE: We determined growth and birth weight-related
      changes of S' to establish reference values in preterm and term neonates.
      METHODS: A prospective study was conducted in a group of 290 preterm and term
      neonates (gestational age 26 + 0 to 40 + 6 weeks of gestation; birth weight 660
      4,460 g). A correlation of S' values with established tricuspid annular plane
      systolic excursion (TAPSE) values was performed. RESULTS: The S' ranged from a
      mean of 4.5 cm/s (Z-score +/- 2 SD: 3.6-5.5 cm/s) in preterm neonates in week
      26(0-6) of gestation to 7.8 cm/s (Z-score +/- 2 SD: 5.5-10.1 cm/s) in term
      neonates in week 40(0-6) of gestation. The S' values increased from 26 to 40
      weeks of gestation. S' and week of gestation are strongly correlated: Pearson's
      correlation coefficient was 0.66 for week of gestation - S' (p < 0.001). A
      significant correlation was found between S' and TAPSE values (r = 0.67; p <
      0.001). CONCLUSION: Z-scores of S' values were calculated and percentile charts
      were established to serve as reference data for preterm and term neonates with
      structurally normal hearts.

PMID- 23548494
TI  - Differences between users and non-users of complementary and alternative medicine
      among people with multiple sclerosis in Denmark: a comparison of descriptive
      characteristics.
AB  - AIMS: The aim of this study was to investigate differences in socio-economic
      characteristics between CAM users and CAM non-users among people with MS in
      Denmark as well as differences in characteristics related to the use of CAM among
      CAM users and the use of conventional treatments among CAM non-users. METHODS: An
      internet-based questionnaire was used to collect data from 3361 patient members
      of the Danish MS society. A letter with a personal code was sent to all
      respondents, asking them to fill out the questionnaire online. Reminders to non
      respondents were sent twice and the final response rate was 55.5%. Statistical
      associations were presented as odds ratios and with respective 95% confidence
      intervals. RESULTS: People with MS in Denmark use a wide range of CAM treatments
      for a variety of reasons. CAM users were more likely to be of female gender, 18
      40 years of age, educated at bachelor level or above, and have a high income
      compared to CAM non-users (p < 0.05). CAM users more often addressed non
      specific/preventive treatment purposes through their use of CAM treatments, they
      communicated less often with a medical doctor about the CAM treatments used, and
      they experienced less side effects as well as less positive effects from the CAM
      treatments used when compared with the use of conventional treatments among CAM
      non-users (p < 0.05). CONCLUSIONS: People with MS in Denmark reported use of a
      large range of CAM treatments. CAM users differed from CAN non-users in relation
      to socio-economic factors as well as treatment characteristics.

PMID- 23548495
TI  - Model-based analysis of multiple electrode array stimulation for epiretinal
      visual prostheses.
AB  - OBJECTIVE: Epiretinal stimulation, which uses an array of electrodes implanted on
      the inner retinal surface to relay a representation of the visual scene to the
      neuronal elements of the retina, has seen considerable success. The objective of
      the present study was to quantify the effects of multi-electrode stimulation on
      the patterns of neural excitation in a computational model of epiretinal
      stimulation. APPROACH: A computational model of retinal ganglion cells was
      modified to represent the morphology of human retinal ganglion cells and
      validated against published experimental data. The ganglion cell model was then
      combined with a model of an axon of the nerve fiber layer to produce a population
      model of the inner retina. The response of the population of model neurons to
      epiretinal stimulation with a multi-electrode array was quantified across a range
      of electrode geometries using a novel means to quantify the model response-the
      minimum radius circle bounding the activated model neurons as a proxy for the
      evoked phosphene. MAIN RESULTS: Multi-electrode stimulation created unique
      phosphenes, uch that the number of potential phosphenes can far exceed the number
      of electrode contacts. SIGNIFICANCE: The ability to exploit the spatial and
      temporal interactions of stimulation may be critical to improvements in the
      performance of epiretinal prostheses.

PMID- 23548496
TI  - Clinical pattern of toxoplasmic retinochoroiditis in a Spanish referral center.
AB  - BACKGROUND/AIMS: To analyze the clinical pattern of ocular toxoplasmosis in a
      referral center in Spain. METHODS: The medical records of consecutive patients
      with ocular toxoplasmosis admitted from a single referral center for uveitis in
      Barcelona (Spain) were retrospectively analyzed between January 2005 and January
      2011. RESULTS: One hundred and thirteen eyes from 113 patients (74 Spanish and 39
      South American) with active ocular toxoplasmosis were analyzed with a 12-month
      follow-up. Final BCVA <= 20/200 was found in 30 eyes (26.5%). The most frequent
      complications were macular edema (16.8%) and epiretinal membrane (11.5%).
      Anterior chamber cell scores of >= 2+ (p = 0.003), vitreous cell scores of >= 2+
      (p = 0.001), and the presence of cataracts (p = 0.047) or serous retinal
      detachment (p = 0.008) were more common among the South American than Spanish
      cohort. Active macular lesions (p < 0.001) with an initial BCVA <= 20/200 (p <
      0.001) and advanced age (p = 0.019) were predictors for final BCVA <= 20/200,
      whereas female gender (p = 0.021) and an initial BCVA <=20/200 (p = 0.045) were
      predictors for ocular complications. Moreover, a BCVA <= 20/200 (p < 0.001) and a
      vitreous cell score of >= 2+ (p = 0.045) at the initial examination were
      predictors of an eventual need for ocular surgery. CONCLUSION: The clinical
      features of ocular toxoplasmosis in Spanish patients differ from those of South
      American patients. In general, active macular lesions with an initial BCVA <=
      20/200 and advanced age were shown to be predictors for final BCVA <= 20/200 in
      our patient cohort.

PMID- 23548497
TI  - A giant adrenal pseudocyst mimicking an adrenal cancer: case report and review of
      the literature.
AB  - Adrenal pseudocysts are rare lesions that develop within the adrenal glands,
      generally from vessel ectasia or from degenerative adenomas or hematomas. They
      are usually non-functional and asymptomatic. The reported potential malignant
      transformation of an adrenal cyst is ca. 7% and indicates radical excision of
      these masses. We report the case of a 69-year-old man with hypertension, chronic
      obstructive pulmonary disease, and obesity in whom microscopic hematuria was
      detected during a routine examination performed by his family doctor. To
      investigate the cause of this microscopic hematuria, the patient underwent
      computed tomography of the abdomen, which showed a well-defined 12-cm lesion of
      the left adrenal gland with calcification and necrotic components that was
      compressing the left kidney, pancreas, and spleen. Suspecting adrenal carcinoma,
      after preoperative staging, a left subcostal laparotomy was performed, with
      resection of the left adrenal gland, a splenectomy, and resection of the
      pancreatic tail. The histology showed an adrenal pseudocyst with a fibrous
      capsule containing amorphous eosinophilic material with calcification and
      cholesterol crystals. The patient's postoperative course was uneventful, and he
      was discharged 12 days after surgery.

PMID- 23548498
TI  - Training cerebrospinal fluid leak repair with nasoseptal flap on the lamb's head.
AB  - BACKGROUND: One of the major challenges of cranial base surgery is reconstruction
      of dural defects and cerebrospinal fluid leak closure. Various grafting methods
      have been used for smaller skull base defects with great success. The indications
      for endoscopic reconstruction have recently evolved to encompass much larger
      breeches in the skull base following tumor removal, thus emphasizing the need for
      vascularized tissue flaps for reconstruction. METHODS: Some authors proposed a
      pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium, which is
      very vascularized and has quite a large surface. It is also long enough to easily
      cover even larger defects of the skull base. The elevation of a nasoseptal flap
      is based on a particularly advanced surgical technique and thus requires proper
      training before being performed in a real patient. RESULTS: Anatomical
      differences between human and lamb heads were observed and explained although
      they do not affect the procedure of the elevation of the nasoseptal flap.
      CONCLUSIONS: The lamb's head has been shown to be an ideal model for the adequate
      training of the surgical skills required for this demanding procedure.

PMID- 23548499
TI  - Socio-economic disparities in the distribution of cardiovascular risk in chronic
      kidney disease stage 3.
AB  - BACKGROUND/AIMS: For most people with chronic kidney disease (CKD),
      cardiovascular disease (CVD) risk exceeds risk of progression to end-stage renal
      disease. This study aimed to investigate the distribution of cardiovascular risk
      in CKD stage 3 by socio-economic status (SES; measured by area deprivation and
      educational attainment) and CKD diagnosis awareness. METHODS: 1,741 patients with
      CKD 3 recruited from primary-care practices for the Renal Risk in Derby Study
      were assessed for cardiovascular risk factors. Ten-year cardiovascular risk,
      estimated using Framingham and QRISK2 risk prediction algorithms in eligible
      subgroups, was dichotomised at >= 20% (a threshold for clinical action in the
      UK), and compared by SES and awareness of CKD diagnosis using logistic
      regression. RESULTS: Patients with lower SES had greater adjusted odd ratios (OR)
      of smoking, diabetes and previous CVD, but not of central obesity, hypertension,
      elevated total/high-density-lipoprotein cholesterol ratio or albuminuria. Using
      Framingham scoring (n = 672), the adjusted OR of having >= 20% 10-year risk were
      2.87 [95% confidence interval (CI) 1.41-5.84] in the lowest deprivation quintile
      compared to the highest, 2.52 (95% CI: 1.52-4.00) in those without qualifications
      compared to those with qualifications, and 1.54 (95% CI: 1.09-2.17) in those
      unaware of their CKD diagnosis compared to those aware of it. QRISK2 scoring (n =
      1,071) showed a similar association with education status [OR: 2.45 (95% CI: 1.63
      3.67)] and lack of CKD awareness [OR: 1.46 (95% CI: 1.05-2.03)], but not with
      deprivation [OR: 1.12 (95% CI: 0.55-2.27)]. CONCLUSION: An elevated CVD risk is
      associated with a lower education status and lack of awareness of CKD diagnosis
      in people with CKD 3.

PMID- 23548500
TI  - The role of depression in medication adherence among heart failure patients.
AB  - The purpose of the study was to explore the association between depression and
      medication adherence in heart failure (HF) patients. Studies have shown that
      people with depression are likely to be nonadherent to their prescribed
      medication treatment. But other studies suggest that nonadherence may be
      overestimated by people with depression. A total of 244 adults with Stage C HF
      completed the study. Self-reported medication adherence was obtained using the
      Basel Assessment of Adherence Scale (BAAS); objective data on medication
      adherence were collected using the electronic Medication Event Monitoring System
      (MEMS). Depression was measured via self-report with the Patient Health
      Questionnaire (PHQ-9). There was a significant difference between depressed and
      nondepressed participants in self-reported medication nonadherence (p = .008),
      but not in objectively measured medication nonadherence (p = .72). The depressed
      sample was 2.3 times more likely to self-report poor medication adherence than
      those who were nondepressed (p = .006). 

PMID- 23548501
TI  - Effects of informational sessions on anxiety precardiovascular procedure.
AB  - To measure the effect of an informational video intervention (IVI) compared to
      standard care (SC) preparation on anxiety and satisfaction prior to percutaneous
      cardiovascular procedure (PCVP). A quasi-experimental, randomized, prepost design
      was used to measure the effect of IVI, provided pre-PCVP, compared with SC only
      preparation on admission anxiety compared with post the IVI and SC preparation.
      There were 113 males/72 females, mean age of 61.8 years, assigned to IVI (n = 94)
      or SC group (n = 91). After the preparatory information session, there was no
      difference between groups on state anxiety (37.6 +/- 11.7 vs. 36.3 +/- 10.7; z = 
      .500, p = .617). There was a significant improvement in satisfaction in IVI group
      (54.23 +/- 5.5 vs. 50.7 +/- 6.6 (z = -2.9, p = .003). IVI session improved
      satisfaction with preparation. Viewing the IVI within hours of a PCVP did not
      reduce measurable anxiety. Further research may reveal a more ideal viewing time.

PMID- 23548502
TI  - Use of per rectal portal scintigraphy to detect portal hypertension in sinusoidal
      obstructive syndrome following unrelated cord blood transplantation.

PMID- 23548503
TI  - Rice allergy demonstrated by double-blind placebo-controlled food challenge in
      peach-allergic patients is related to lipid transfer protein reactivity.
AB  - BACKGROUND: The risk factors for sensitisation to rice and the involved allergens
      are still partially unknown. In this study we evaluated the clinically relevant
      aspects of rice allergy in DBPCF-positive patients, the major rice allergens, the
      severity of peach- and rice-induced symptoms in respect to Pru p 3 sensitisation
      and the role of anti-rPru p 3 IgE levels as a risk factor for rice allergy.
      METHODS: In 148 peach-allergic subjects, patients with allergic reactions to rice
      and rice-positive serum IgE were selected. Symptoms were verified by double-blind
      placebo-controlled food challenges (DBPCFCs), performed at a maximum dosage of 25
      g. Rice allergens, identified by IgE immunoblotting, were characterised by N
      terminal amino acid sequencing. The relationship between anti-rPru p 3, 1 and 4
      IgE levels and rice symptoms were statistically analysed. RESULTS: Eight out of
      10 recruited rice-allergic patients had positive DBPCFCs, while 2 patients were
      not challenged due to their previously documented severe reactions. All patients
      with rice-induced symptoms were Pru p 3 positive and presented with higher anti
      rPru p 3 levels than the rice-sensitised but tolerant patients. A 9-kDa lipid
      transfer protein, which was highly homologous to Pru p 3, was identified as the
      major rice allergen and elicited a positive response in all of the patients. Five
      patients reacted to a putative 15- to 17-kDa rice allergenic protein, and 3
      patients reacted to an [alpha]-amylase/subtilisin inhibitor that was
      approximately 20 kDa. CONCLUSION: Rarely, allergic reactions to rice can arise in
      patients with peach allergies who are sensitised to Pru p 3, particularly in
      patients with high anti-rPru p 3 IgE levels.

PMID- 23548504
TI  - Capacity of N4-methyl-2'-deoxycytidine 5'-triphosphate to sustain the polymerase
      chain reaction using various thermostable DNA polymerases.
AB  - The dCTP analog N4-methyl-2'-deoxycytidine 5'-triphosphate (N4medCTP) was
      evaluated for its performance in the polymerase chain reaction (PCR). Using the
      HotStart Taq DNA polymerase with a standard thermal protocol, test segments 85 or
      200 bp long were amplified equally well using dCTP or N4medCTP:dCTP mixtures
      ranging in molar ratio from 3:1 to 10:1, while complete replacement of dCTP by
      N4medCTP gave clearly lower amplicon yields and higher Cq values. Comparable
      yields with N4medCTP or dCTP were achieved only by using a slowdown protocol.
      Post-PCR melting analyses showed decreasing Tm values for amplicons obtained with
      increasing N4medCTP:dCTP input ratios; for the 200-bp amplicon, complete
      replacement of dCTP by N4medCTP in the reaction reduced the Tm by 11  degrees C;
      for the 85-bp amplicon the Tm reduction was 7  degrees C. In experiments aiming
      at the 200-bp amplicon, Pfu exo(-) DNA polymerase did not sustain PCR when dCTP
      was fully replaced by N4medCTP, even with the slowdown protocol, except at
      elevated N4medCTP concentrations, and, compared to PCR conducted exclusively with
      dCTP, the use of N4medCTP:dCTP mixtures gave reduced yields and distinctly higher
      Cq values, regardless of the thermal program employed. PCR experiments with 9
      degrees N DNA polymerase using N4medCTP in the conventional thermal protocol
      failed to produce the 200-bp amplicon.

PMID- 23548505
TI  - Anterior surgical approaches to the cervicothoracic junction: when to use the
      manubriotomy?
AB  - BACKGROUND CONTEXT: The cervicothoracic junction (CTJ) is always a difficult area
      for anterior approaches. Among them, low anterior cervical approach alone or
      combined with manubriotomy is the most frequently used. PURPOSE: To study the
      need of manubriotomy. STUDY DESIGN/SETTING: Comparison of last guidelines
      proposed in literature. PATIENT SAMPLE: Seven patients treated between March 2010
      and March 2011. METHODS: All the patients were scanned on with computed
      tomography and magnetic resonance of the spinal column before surgery.
      Measurements by Teng and Karikari were applied in all the cases. An illustrative
      case is showed. RESULTS: The anterior approaches to the CTJ are reviewed. The
      most recent guidelines by Teng and Karikari are easy to apply and careful. The
      results obtained were the same in all the cases with good outcome. CONCLUSIONS:
      Manubriotomy permits a good exposure of the CTJ area with a low rate of
      complications. Either Teng and Karikari's guidelines can be used to estabilish
      the need of manubriotomy.

PMID- 23548506
TI  - Study of the prevalence and interobserver reproducibility of radiologic images
      suggestive of urethral diverticula in men with spinal cord injury.
AB  - OBJECTIVES: To determine the prevalence of radiologic images suggestive of
      urethral diverticula (UD) in men with spinal cord injury (SCI) and to study the
      interobserver diagnostic reproducibility. METHODS: Radiological studies (i.e.
      voiding cystourethrography and retrograde urethrography) performed over 1 year on
      men with SCI were independently reviewed by 3 researchers (1 urologist and 2
      radiologists). RESULTS: The prevalence of UD was found to be between 4.2 and 9.8%
      of the patients, the higher figure obtained when including also the doubtful
      images. The kappa index of agreement between the researchers was low (between
      0.15 and 0.40). The factors that significantly influenced agreement were
      localization in the prostatic urethra (p = 0.021), localization in the penile
      urethra (p = 0.000) and fusiform morphology (p = 0.004). Logistic regression
      analysis showed that the variables that independently influenced diagnostic
      agreement were the following: localization in the penile urethra (in favor of
      agreement) and fusiform morphology (against agreement). CONCLUSIONS: Radiologic
      images suggestive of UD constitute a frequent finding in men with SCI and raise
      important diagnostic problems.

PMID- 23548507
TI  - Ancient gut microbiomes shed light on modern disease.

PMID- 23548508
TI  - Retrofitting impervious urban infrastructure with green technology for rainfall
      runoff restoration, indirect reuse and pollution load reduction.
AB  - The built environs alter hydrology and water resource chemistry. Florida is
      subject to nutrient criteria and is promulgating "no-net-load-increase" criteria
      for runoff and constituents (nutrients and particulate matter, PM). With such
      criteria, green infrastructure, hydrologic restoration, indirect reuse and source
      control are potential design solutions. The study simulates runoff and
      constituent load control through urban source area re-design to provide long-term
      "no-net-load-increases". A long-term continuous simulation of pre- and post
      development response for an existing surface parking facility is quantified.
      Retrofits include a biofiltration area reactor (BAR) for hydrologic and
      denitrification control. A linear infiltration reactor (LIR) of cementitious
      permeable pavement (CPP) provides infiltration, adsorption and filtration.
      Pavement cleaning provided source control. Simulation of climate and source area
      data indicates re-design achieves "no-net-load-increases" at lower costs compared
      to standard construction. The retrofit system yields lower cost per nutrient load
      treated compared to Best Management Practices (BMPs). 

PMID- 23548509
TI  - The Outer Loop bioreactor: a case study of settlement monitoring and solids
      decomposition.
AB  - The Outer Loop landfill bioreactor (OLLB) located in Louisville, KY, USA has been
      in operation since 2000 and represents an opportunity to evaluate long-term
      bioreactor monitoring data at a full-scale operational landfill. Three types of
      landfill units were studied including a Control cell, a new landfill area that
      had a piping network installed as waste was being placed to support leachate
      recirculation (As-Built cell), and a conventional landfill that was modified to
      allow for liquid recirculation (Retrofit cell). The objective of this study is to
      summarize the results of settlement data and assess how these data relate to
      solids decomposition monitoring at the OLLB. The Retrofit cells started to settle
      as soon as liquids were introduced. The cumulative settlement during the 8years
      of monitoring varied from 60 to 100cm. These results suggest that liquid
      recirculation in the Retrofit cells caused a 5-8% reduction in the thickness of
      the waste column. The average long-term settlement in the As-Built and Control
      Cells was about 37% and 19%, respectively. The modified compression index
      (Calpha(')) was 0.17 for the Control cells and 0.2-0.48 for the As-Built cells.
      While the As-Built cells exhibited greater settlement than the Control cells, the
      data do not support biodegradation as the only explanation. The increased
      settlement in the As-Built bioreactor cell appeared to be associated with liquid
      movement and not with biodegradation because both chemical (biochemical methane
      potential) and physical (moisture content) indicators of decomposition were
      similar in the Control and As-Built cells. The solids data are consistent with
      the concept that bioreactor operations accelerate the rate of decomposition, but
      not necessarily the cumulative loss of anaerobically degradable solids. 

PMID- 23548510
TI  - The influence of slaughterhouse waste on fermentative H2 production from food
      waste: preliminary results.
AB  - The aim of this study was to evaluate the influence of slaughterhouse waste (SHW;
      essentially the skin, fats, and meat waste of pork, poultry, and beef) in a
      fermentative co-digestion process for H2 production from pre-selected organic
      waste taken from a refectory (food waste [FW]). Batch tests under mesophilic
      conditions were conducted in stirred reactors filled with different proportions
      of FW and SHW. The addition of 60% and 70% SHW to a mixture of SHW and FW
      improved H2 production compared to that in FW only, reaching H2-production yields
      of 145 and 109 ml g VS 0(-1), respectively, which are 1.5-2 times higher than
      that obtained with FW alone. Although the SHW ensured a more stable fermentative
      process due to its high buffering capacity, a depletion of H2 production occurred
      when SHW fraction was higher than 70%. Above this percentage, the formation of
      foam and aggregated material created non-homogenous conditions of digestion.
      Additionally, the increasing amount of SHW in the reactors may lead to an
      accumulation of long chain fatty acids (LCFAs), which are potentially toxic for
      anaerobic microorganisms and may inhibit the normal evolution of the fermentative
      process.

PMID- 23548511
TI  - Defatted milk is preferred by Mexican school-age children over whole milk in a
      sensorial study.
AB  - OBJECTIVE: To compare the liking, flavor and texture of whole, partially defatted
      and defatted cow's milk using sensory tests. MATERIALS AND METHODS: Children aged
      6-16 years, living in indigenous boarding schools in the State of Hidalgo,
      Mexico, tested samples of whole, partially defatted and defatted cow's milk and
      answered a questionnaire that explored liking, flavor and texture through ad hoc
      designed scales. The differences in response proportions were analyzed by chi2
      tests and multinomial logistic regression models. RESULTS: Tests were completed
      by 165 children (79 girls and 86 boys). Rated by habitual consumers of whole,
      partially defatted and defatted milk, liking (70.6-77.8%, liked it very much),
      flavor (72.5-77.8%, very tasteful) and texture (41.3-54.9%, not creamy or watery)
      were better rated for defatted than for whole milk [liking (19.6-29.4%, p <
      0.001, liked it very much), flavor (19.6-39.7%, p < 0.001, very tasty) and
      texture (27.5-39.2%, p < 0.05, not creamy or watery)]. The global preference was
      higher for defatted (74.5-81.0%) than for whole milk (6.3-15.7%, p < 0.001).
      CONCLUSIONS: Defatted milk (0.5%) can be introduced into public programs to
      reduce the saturated fat intake or control obesity in children older than 6 years
      in elementary schools.

PMID- 23548512
TI  - Constant and variable amplitude ultrasonic fatigue of 2024-T351 aluminium alloy
      at different load ratios.
AB  - Ultrasonic fatigue testing equipment is presented that is capable of performing
      constant amplitude (CA) and variable amplitude (VA) experiments at different
      constant load ratios. This equipment is used to study cyclic properties of
      aluminium alloy 2024-T351 in the high cycle fatigue (HCF) and very high cycle
      fatigue (VHCF) regime at load ratios R=-1 and R=0.5. CA loading does not reveal a
      fatigue limit below 1010 cycles. Cracks leading to VHCF failure start at broken
      constituent particles. Specimens that survived more than 1010 cycles at R=-1
      contain non-propagating cracks of lengths below grain size. Resonance frequency
      and nonlinearity parameter beta(rel) show changes of vibration properties of
      specimens at low fractions of their VHCF lifetime. VA lifetimes are measured in
      the HCF and VHCF regime and compared with Miner calculations. Damage sums
      decrease with decreasing load (and increasing mean lifetimes) and are lower for
      R=0.5 than R=-1.

PMID- 23548513
TI  - High prevalence of autoimmune thyroiditis in children and adolescents with
      vitiligo.
AB  - BACKGROUND/AIMS: Vitiligo is considered to be an autoimmune disease and is known
      to be associated with other autoimmune diseases, particularly affecting the
      thyroid. In children and adolescents this association has been reported in only a
      few studies, with varying results. The aim of this study was to examine thyroid
      function and prevalence of thyroid autoimmunity in children and adolescents with
      vitiligo and to investigate the utility of screening. METHODS: Two hundred and
      sixty patients with vitiligo were enrolled. Plasma TSH, FT4 and anti-thyroid
      peroxidase (TPO) antibody concentrations were measured. The prevalence of thyroid
      dysfunction and autoimmunity were compared to the general healthy paediatric
      population. RESULTS: Autoimmune thyroiditis (AIT) with thyroid hormone
      disturbances was diagnosed in 16 patients (6.2%). This is significantly higher
      than the prevalence reported in the general healthy paediatric population.
      Increased levels of anti-TPO antibodies (= 30 kU/l), without thyroid hormone
      disturbances, were found in 27 patients (10.5%). CONCLUSION: The prevalence of
      AIT in children and adolescents with vitiligo is significantly higher than in the
      general population. It may be advantageous to screen thyroid function and
      antibody levels in all paediatric patients with non-segmental vitiligo. To
      strengthen recommendations on screening, research on the burden for patients and
      cost-effectiveness is needed.

PMID- 23548514
TI  - Effect of lipopolysaccharide mediating early- and late- activated THP-1
      macrophages on ECV304 endothelial cell dysfunction: dysregulation of secretion of
      VEGF and proliferation and migration of ECV304.
AB  - OBJECTIVE: To investigate the different effects of lipopolysaccharide (LPS)
      mediating early and late activated THP-1 macrophages (Mphi) on ECV304 endothelial
      cell dysfunction: dysregulation of secretion of VEGF and proliferation, and
      migration of ECV304. METHODS: The inflammatory Mphi was divided into early phase
      (2 h) group and late phase (24 h) group according the different exposure time to
      LPS. Then the inflammatory Mphi and ECV304 were co-cultured via transwell
      chambers in both non-contacting and contacting systems. The levels of VEGF were
      determined by ELISA, and the proliferation index and apoptosis of ECV304 were
      analyzed by FACSCalibur. The migration of ECV304 was tested by modified Boyden
      chamber assay. RESULTS: The level of VEGF and the proliferation of ECV304 cell
      were increased more apparently in early-phase Mphi-treated group. But the
      proportion of early apoptotic and late apoptotic/necrotic cells in late-phase
      Mphi-treated group were higher than that of the former. Migration rate of ECV304
      was enhanced in early-phase Mphi-treated group. All those effects were more
      significant in contacting system comparing with no-contacting system. CONCLUSION:
      Early-activated macrophages (mediated by LPS) could increase the secretion of
      VEGF and promote the proliferation and migration of ECV304; while the late
      activated macrophages could promote/enhance the apoptosis of ECV304 more
      significant in contacting system when (it was) compared with no-contacting
      system.

PMID- 23548515
TI  - Impaired force steadiness is associated with changes in force frequency
      composition in subacute stroke.
AB  - We tested the hypothesis that impaired force steadiness early after stroke is
      associated with changes in frequency composition of the force signal during
      constant-force task. The power spectra and the relationship between power spectra
      and force variability during isometric knee extension (10%, 20%, 30%, and 50% of
      peak torque for 10s) were studied in the paretic and non-paretic legs of 34
      stroke patients (64+/-14years, 8-25days post-injury) and the dominant leg of 20
      controls (62+/-10years). Power spectrum analysis of the force signal included the
      median frequency, peak power frequency, relative peak power, and relative power
      in 0-3, 4-6, and 8-12Hz bands. Force variability, quantified by coefficient of
      variation (CV), was increased in patients at 3 of the 4 contraction levels
      (P?0.001). Median frequency across all force levels was decreased and the
      relative peak power was increased in the paretic and non-paretic legs compared to
      controls (P?0.001). The relative power was increased in 0-3Hz band and decreased
      in both 4-6 and 8-12Hz bands in the paretic leg only (P?0.001). Progressively
      stronger contractions brought about a significant decrease in relative power in
      the 0-3Hz band and increase in 8-12Hz band in controls but not in stroke
      subjects. The hypothesis was confirmed by significant non-linear correlations
      between CV and each relative spectral power found in the paretic leg at most
      contraction levels (0.22?R(2)?0.72, P?0.0004) and in the non-paretic leg at 10%
      only (0.35?R(2)?0.52, P?0.0002), but not in controls. Fugl-Meyer lower extremity
      motor and sensory scores were not related to the frequency measures in stroke
      subjects (P>0.05). Limited modulation of frequency spectra and the emergence of
      non-linear relation between power spectra and force variability suggest that less
      broadband force output may account in part for impaired force steadiness in
      paretic and non-paretic legs early after stroke.

PMID- 23548516
TI  - Intrathecal granulocyte colony-stimulating factor modulate glial cell line
      derived neurotrophic factor and vascular endothelial growth factor A expression
      in glial cells after experimental spinal cord ischemia.
AB  - The hematopoietic growth factor, granulocyte colony-stimulating factor (G-CSF),
      has become one of the few growth factors approved for clinical use. It has
      therapeutic potential for numerous neurodegenerative diseases; however, at
      present the cellular effects of G-CSF on the central nervous system remain
      unclear and in need of investigation. In the present study, we used spinal cord
      ischemia, a neurodegenerative model, to examine the effects of intrathecal (i.t.)
      G-CSF on glial cell (microglia and astrocyte) activation and neuroprotective
      factor expression, including glial cell line-derived neurotrophic factor (GDNF)
      and vascular endothelial growth factor A (VEGF-A) protein expression. Our results
      indicate that i.t. G-CSF could enhance ischemia-induced microglial activation and
      inhibit ischemia-induced astrocyte activation. Both GDNF and VEGF-A are
      upregulated after injury, and i.t. G-CSF could enhance GDNF and VEGF-A
      expressions after injury. Interestingly, our results indicate that performing
      i.t. G-CSF alone on normal animals could have the effect of microglial and
      astrocyte activation and enhanced GDNF and VEGF-A expressions. Furthermore,
      through laser scanning confocal microscopy, we found that astrocytes may
      contribute to the majority of GDNF and VEGF-A expressions of G-CSF after spinal
      cord ischemia. Overall, this G-CSF-induced upregulation suggests that activation
      of endogenous neuroprotective mechanisms could resist neurodegenerative insults.
      These observations demonstrate the cellular mechanism of i.t. G-CSF after spinal
      cord ischemia and confirm the neuroprotective effect of G-CSF after spinal cord
      ischemia injury.

PMID- 23548517
TI  - From a regional cohort of extremely low birth weight infants: cardiac function at
      the age of 7 years.
AB  - BACKGROUND: The long-term impact of prematurity on cardiac structure and function
      has not yet been fully discovered. OBJECTIVES: To assess long-term cardiac
      complications in the regional cohort of extremely low birth weight (ELBW)
      children born in 2002-2004. MATERIAL AND METHODS: Eighty-one children born as
      ELBW infants (91% of the available cohort) with a median birth weight of 890 g
      (25-75th percentile: 760-950) were evaluated at the mean age of 6.7 years. The
      control group included 40 children born full-term, selected from one general
      practice in the district. Echocardiography and 24-hour ambulatory blood pressure
      measurements (ABPM) were performed. The primary outcome variable was the presence
      of cardiac complications such as left ventricular hypertrophy (LVH), diastolic
      dysfunction or systolic dysfunction. RESULTS: LVH was diagnosed in 4/81 ELBW
      children and 2/40 control children (p = 1.0). Concentric remodeling was detected
      in 8 (10%) subjects from the ELBW group and in 2 (5%) from the control group (p =
      0.49). There were no patients with diastolic or systolic dysfunction in either
      group. After having expressed the results of M-mode echocardiography as z-scores
      for body surface area (BSA), statistically significant differences were observed
      for right-ventricle dimension in diastole (-1.49 +/- 1.25 vs. -0.31 +/- 0.91; p <
      0.001), LV inner dimension in diastole (-0.53 +/- 1.26 vs. 0.13 +/- 0.94; p =
      0.01) and left atrium (-0.93 +/- 1.07 vs. -0.15 +/- 1.02; p < 0.01). Heart rate
      (HR) was significantly faster in ELBW children (92.9 +/- 8.4 vs. 86.7 +/- 7.4
      bpm; p = 0.01 adjusted for BSA) and they also had significantly higher night-time
      blood pressure [mean (z-score): 1.15 vs. 0.2; p = 0.02] without nocturnal dipping
      (night-time dipping <10%: 13 (16.7%) vs. 2 (5.2%), p = 0.13). CONCLUSIONS: No
      differences were found between the groups in the occurrence of cardiac
      complications. Ex-preterm ELBW children at age 6 may have a faster HR, smaller
      cardiac dimensions on echocardiography and higher nocturnal blood pressure. The
      clinical relevance of these findings is unknown.

PMID- 23548518
TI  - I'm not strange, I'm just like you.

PMID- 23548519
TI  - Benefits of exercise in asthma.

PMID- 23548520
TI  - Terminology, close-calls, and bracketology for allergy, asthma, and immunology.

PMID- 23548521
TI  - Asthma and frequency of wheeze: risk factors for the persistence of atopic
      dermatitis in children.
AB  - BACKGROUND: Studies have examined the development of asthma in children with
      atopic dermatitis (AD); however, none have looked at the association of asthma or
      the frequency of wheeze with respect to persistence or difficulty in achieving AD
      clinical improvement in children. OBJECTIVE: To determine whether children with
      AD who have asthma and increasing frequency of wheezing have more persistent AD.
      METHODS: This is a cohort study using the Pediatric Eczema Elective Registry
      (PEER) database, which includes data obtained at enrollment and 3 years later.
      The AD outcome was the persistence of skin symptoms. Our covariates of interest
      were asthma diagnosis and wheezing symptoms, which were measured at enrollment
      and again at year 3 of the study. Multivariate logistic regression models
      assessed the magnitude of associations among AD symptoms, asthma diagnosis, and
      the frequency of wheeze. All models were adjusted for sex, age, and ethnicity.
      RESULTS: A total of 2104 children were enrolled in the PEER study and had at
      least 3 years of follow-up at the time of this study. At enrollment, an asthma
      diagnosis decreased the likelihood of being rash free in the preceding 6 months
      by 30% (odds ratio, 0.70; 95% confidence interval, 0.59-0.84). At year 3, having
      asthma decreased the likelihood by 40% (odds ratio, 0.60; 95% confidence
      interval, 0.49-0.72). Increasing frequency of wheezing also decreased the
      likelihood that a child was rash free (P < .001). CONCLUSION: For children with
      AD, a history of asthma and an increasing frequency of wheezing correlate
      strongly with more persistent AD.

PMID- 23548522
TI  - Role of vascular endothelial growth factor antagonism on airway remodeling in
      asthma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is an important mediator of
      the neoangiogenesis component of remodeling in asthma. OBJECTIVE: To evaluate the
      influence of VEGF blockage on airway remodeling, specifically epithelium
      thickness, subepithelial smooth muscle thickness, number of mast and goblet
      cells, and basement membrane thickness, in a mouse model of chronic asthma.
      METHODS: We used 30 BALB/c mice. The control group was not exposed to ovalbumin
      or any medication (group 1). Other groups were exposed to intraperitoneal and
      inhaled ovalbumin to achieve chronic asthma. Each of these groups received
      intraperitoneal saline (group 2), intraperitoneal dexamethasone (group 3), or
      intraperitoneal bevacizumab (group 4). Histomorphologic examination for
      epithelium thickness, subepithelial smooth muscle thickness, number of mast and
      goblet cells, and basement membrane thickness was performed from the middle zone
      of the left lung. RESULTS: Treatment with anti-VEGF caused significant reduction
      in epithelial, subepithelial muscle, and basement membrane thickness compared
      with untreated asthmatic mice (P = .001, P = .03, and P = .009, respectively).
      Goblet and mast cell numbers were significantly lower in mice treated with anti
      VEGF than in untreated mice (P = .02 and P = .007, respectively). Dexamethasone
      treatment resulted in improvement of all histomorphologic markers, except goblet
      cell number. Influences of dexamethasone and anti-VEGF on epithelial and basement
      membrane thickness and mast and goblet cell numbers did not differ (P > .05), but
      subepithelial muscle layer was thinner in the former (P = .003). CONCLUSION: VEGF
      blockage may provide adjunctive therapeutic options as steroid-sparing agents for
      more effective treatment of remodeling in asthma.

PMID- 23548523
TI  - Influence of beta(2)-adrenergic receptor polymorphisms on asthma exacerbation in
      children with severe asthma regularly receiving salmeterol.
AB  - BACKGROUND: New evidence suggests that different beta(2)-adrenergic receptor
      (beta2AR) polymorphisms may influence asthma control in patients receiving long
      acting beta(2)agonists (LABAs) as regular therapy. OBJECTIVES: To determine the
      influence of beta2AR polymorphisms on asthma exacerbations in children with
      severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs
      regularly. METHODS: Ninety-seven children with severe asthma were genotyped for
      polymorphisms of beta2AR at codons 16 and 27. The number of severe exacerbations,
      the time of first asthma exacerbation, and the number of hospitalizations during
      12 months were assessed. Changes on pulmonary function from the beginning to the
      end of the study were also evaluated. RESULTS: The number of overall asthma
      exacerbations and the proportion of children with these events were similar among
      beta2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position
      27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was
      similar among individuals carrying different beta2AR polymorphisms. No beta2AR
      genotype association was found in relation to the number of hospitalizations.
      Longitudinal analysis of forced expiratory volume in 1 second from baseline to
      the end of the study also showed no differences among beta2AR genotypes at
      position 16 or 27. No association was observed among the 3 most common haplotypes
      (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of
      participants with asthmatic crisis or with the overall number of exacerbations.
      CONCLUSION: beta2AR polymorphisms were not associated with an increased risk of
      having asthma exacerbations or lung function decline in a population of
      Argentinian children with severe asthma receiving ICS and LABAs regularly.

PMID- 23548524
TI  - Influence of beta(2)-adrenergic receptor polymorphism on methacholine
      hyperresponsiveness in asthmatic patients.
AB  - BACKGROUND: We previously reported that the beta(2)-adrenergic receptor (ADRB2)
      polymorphism had no effect on bronchial hyperresponsiveness (BHR) to methacholine
      in asthmatic patients. We have now replicated this analysis in a different and
      larger cohort of patients. OBJECTIVE: To assess the effect of the ADRB2
      polymorphism in methacholine-responsive patients with asthma. METHODS: We
      conducted a retrospective analysis of the effects of ADRB2 haplotypes at position
      16 (Gly/Arg) and 27(Gln/Glu) in 449 patients with a physician diagnosis of asthma
      who were responsive to methacholine (ie, provocation concentration that caused a
      decrease in forced expiratory volume in 1 second [FEV(1)] of 20% [PC(20)], <8
      mg/mL). RESULTS: No differences were found in age, FEV(1), or inhaled
      corticosteroid dose among the genotypes or haplotypes. No significant differences
      were found in methacholine PC(20) (ie, <8 mg/mL) between the separate genotypes
      at position 16 or 27 or between the haplotypes at positions 16/27 combined. In
      addition, no significant differences were found among individual genotypes when
      stratified according to severity of BHR using different doubling dilution cutoff
      points for methacholine PC(20) (ie, <4 mg/mL, <2 mg/mL, and <1 mg/mL).
      CONCLUSION: We have confirmed in this replication study that common ADRB2
      genotypes or haplotypes at positions 16/27 do not influence BHR in methacholine
      responsive patients with asthma.

PMID- 23548525
TI  - Adherence to imported fire ant subcutaneous immunotherapy.
AB  - BACKGROUND: Imported fire ant (IFA) subcutaneous immunotherapy (SCIT) is safe and
      effective. For optimal protection, SCIT is given monthly for 3 to 5 years.
      Successful outcomes require patient adherence. OBJECTIVE: To evaluate SCIT
      adherence in IFA allergic patients in an endemic area. METHODS: Patients with
      systemic reactions to an IFA sting, with detectable specific IgE, who received a
      recommendation to start IFA SCIT were included. Initial reaction severity and
      demographic data were collected. Patients were contacted at 1 year regarding
      interval reactions to stings, SCIT adherence, and reason for nonadherence.
      Adherence rates were analyzed for association with age, sex, and severity of
      initial reaction. RESULTS: Seventy-six patients were enrolled, and 71% adhered to
      the recommendation to start IFA SCIT. Subgroup analysis did not find significant
      differences. At 1 year, 97% completed follow-up for analysis, and only 35%
      remained adherent. Subgroup analysis did not find significant differences.
      Inconvenience and fear were reported as reasons for not following the
      recommendation to start or continue with IFA SCIT. CONCLUSION: IFA SCIT is a life
      saving therapy that is safe and effective. Despite this, only 71% followed the
      recommendation to start, and at 1 year only 35% remained adherent. Adherence was
      not statistically related to age, sex, or severity of initial reaction.
      Logistical constraints and fear were significant impediments.

PMID- 23548526
TI  - Analysis of hereditary angioedema attacks requiring a second dose of ecallantide.
AB  - BACKGROUND: Effective treatment of acute attacks is critical in managing
      hereditary angioedema (HAE). Ecallantide, a plasma kallikrein inhibitor, is
      approved for the treatment of HAE attacks. Occasionally, a second dose is needed
      when treating attacks of HAE. OBJECTIVE: To evaluate the characteristics of HAE
      attacks requiring a second dose (dose B) of ecallantide. METHODS: Data from all
      ecallantide clinical trials (EDEMA2, EDEMA4, and DX-88/19) that allowed an open
      label dose B were included in this analysis. Patient and attack characteristics
      potentially predictive of dose B after ecallantide were analyzed by logistic
      regression. A multivariate model was built using a backward selection process,
      incorporating variables from the univariate model with P < .20 and removing
      factors with the highest P value until only significant (P < .05) factors
      remained. RESULTS: The analysis included 732 ecallantide-treated HAE attacks in
      179 patients. Dose B was required in 88 attacks (12.0%), most (80.5%) for
      incomplete response. By attack location, 31 of 325 abdominal attacks (9.5%), 17
      of 158 laryngeal attacks (10.8%), and 40 of 242 peripheral attacks (16.5%)
      required dose B. On the basis of the univariate analysis, baseline severity (odds
      ratio = 1.33, P = .15) and peripheral attack (odds ratio = 1.80, P = .01) were
      identified as potential predictive factors; abdominal attacks had an inverse
      correlation (odds ratio = 0.64, P = .055). However, the multivariate analysis
      identified only peripheral attacks as statistically significantly correlated (P <
      .05) with dose B requirement. CONCLUSION: A single, 30-mg dose of ecallantide was
      effective for most HAE attacks (88.0%). Patients with peripheral attacks of HAE
      were more likely to require a second dose of ecallantide after 4 hours. TRIAL
      REGISTRATION: clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial
      was conducted before registration requirements were implemented), NCT00457015 for
      EDEMA4, and NCT00456508 for DX-88/19.

PMID- 23548527
TI  - Relating microarray component testing and reported food allergy and food
      triggered atopic dermatitis: a real-world analysis.
AB  - BACKGROUND: High epitope diversity has been associated with increased IgE
      mediated food allergy severity. OBJECTIVE: To characterize associations between
      results from an automated microarray system and self-reported food allergy and
      food-triggered atopic dermatitis (AD). METHODS: Families with food allergic
      children were identified from a Jewish community in Lakewood, New Jersey, with
      immediate family members without food allergy or food-triggered AD serving as
      controls for the identified children. Sets of microarray components analyzed were
      to milk (Bos d 4, Bos d 5, Bos d 8, Bos d lactoferrin), egg (Gal d 1, Gal d 2,
      Gal d 3, Gal d 5), and peanut (Ara h 1, Ara h 2, Ara h 3, Ara h 6). RESULTS:
      Seventy-three patients from 23 families were recruited. Culprit foods included
      milk (n = 20), egg (n = 10), and peanut (n = 6) for food allergy and milk (n =
      10) and egg (n = 7) for food-triggered AD. Odds of having had a self-reported
      related food allergy or food-triggered AD reaction significantly increased with a
      higher number of detectable microarray components to that food. Ara h 1, Ara h 2,
      and Ara h 6 were individually associated with reported peanut allergy, and Bos d
      4 was individually associated with reported milk allergy. The number of egg
      components significantly increased the odds of having related food-triggered AD.
      CONCLUSION: High diversity of food allergen components relates well to self
      reported history of food allergy and food-associated AD.

PMID- 23548528
TI  - Effect of allergic rhinitis on the expression of human beta-defensin 2 in
      tonsils.
AB  - BACKGROUND: Human beta-defensins (HBDs) are a newly identified family of
      antimicrobial peptides that are expressed by epithelia on mucosal surfaces.
      Exposure of airway epithelial cells to TH2-type cytokines results in a
      significant decrease in the antimicrobial activity of the cells. OBJECTIVE: To
      investigate the effect of allergic rhinitis on the expression of HBD-2 in tonsils
      and adenoids. METHODS: Palatine tonsils and adenoids were obtained from 30
      patients with no history of recurrent tonsillitis. The patients were divided into
      2 groups: allergic rhinitis and nonallergic rhinitis groups. Real-time polymerase
      chain reaction analysis was used to measure messenger RNA (mRNA) levels of HBD-2
      mRNA in tonsil and adenoid tissue samples from the 2 patient groups.
      Immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA) were
      used to evaluate the expression of HBD-2 protein in tonsil and adenoid tissues.
      The concentration of the cytokines interleukin (IL) 4, IL-5, and interferon gamma
      (IFN-gamma) in tissue homogenates was measured by ELISA. RESULTS:
      Immunofluorescent staining data demonstrated the expression of HBD-2 protein in
      the surface epithelia of tonsils, and a marked difference in the staining
      intensity was observed the between 2 groups. HBD-2 mRNA and protein levels in the
      tonsils were significantly lower in the allergic rhinitis group than that in the
      nonallergic rhinitis group (P = .03 and P = .04, respectively). IL-5 and IFN
      gamma were not detected, and no significant difference was found in IL-4
      concentrations in tonsil homogenates between the 2 groups. CONCLUSION: Allergic
      rhinitis suppresses HBD-2, an epithelial antimicrobial peptide, in the tonsils.

PMID- 23548529
TI  - Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare disorder associated with
      episodic attacks of well-demarcated angioedema. Attacks that affect the larynx
      can result in life-threatening airway obstruction. OBJECTIVES: To examine
      efficacy and safety of ecallantide treatment for laryngeal HAE attacks. METHODS:
      Data were combined from 4 clinical studies (EDEMA2, EDEMA3, EDEMA4, and DX-88/19)
      evaluating 30 mg of subcutaneous ecallantide for treatment of acute HAE attacks.
      Efficacy was assessed using 2 validated, HAE-specific, patient-reported outcome
      measures. The change in Mean Symptom Complex Severity (MSCS) score indicates
      change in symptom severity; a negative score indicates improvement. The
      calculated minimally important difference (MID) for change in severity is -0.30.
      The Treatment Outcome Score (TOS) measures treatment response. A positive score
      indicates improvement; the calculated MID is 30. RESULTS: Overall, 98 patients
      received ecallantide for 220 laryngeal attacks. The mean +/- SD change in MSCS
      score was -1.1 +/- 0.73 and -1.6 +/- 0.68 at 4 and 24 hours, respectively. The
      mean +/- SD TOS was 73.5 +/- 35.8 and 85.5 +/- 27.8 at 4 and 24 hours,
      respectively. Median time to significant improvement was 185 minutes (95%
      confidence interval, 167-226). One attack required intubation. Four treatment
      emergent serious adverse events were reported, including 2 HAE attacks that
      resulted in hospitalization and 2 anaphylactic reactions. One of these reactions
      required treatment with epinephrine, but both patients recovered fully. There
      were no deaths. CONCLUSION: In this large attack series, ecallantide was
      effective for treatment of laryngeal HAE attacks. There is a risk of
      hypersensitivity, including anaphylaxis, consistent with product labeling. As
      such, ecallantide should be administered under the supervision of a health care
      professional. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: not applicable
      for EDEMA2 (trial was conducted before implementation of registration
      requirements); NCT00262080 for EDEMA3, NCT00457015 for EDEMA4, and NCT00456508
      for DX-88/19.

PMID- 23548530
TI  - Design validation and labeling comprehension study for a new epinephrine
      autoinjector.
AB  - BACKGROUND: To facilitate the correct use of epinephrine autoinjectors (EAIs) by
      patients and caregivers, a novel EAI (Auvi-Q) was designed to help minimize use
      related hazards. OBJECTIVE: To support validation of Auvi-Q final design and
      assess whether the instructions for use in the patient information leaflet (PIL)
      are effective in training participants on proper use of Auvi-Q. METHODS: Healthy
      participants, 20 adult and 20 pediatric, were assessed for their ability to
      complete a simulated injection by following the Auvi-Q instructions for use.
      Participants relied only on the contents of the PIL and other labeling features
      (device labeling and its instructions for use, electronic voice instructions and
      visual prompts). RESULTS: The mean +/- SD age of the adult and pediatric
      participants was 39.4 +/- 11.6 and 10.9 +/- 2.3 years, respectively. In total,
      80% of adult and 35% of pediatric participants had prior experience with EAIs.
      All adults and 95% of pediatric participants completed a simulated injection on
      the first attempt; 1 pediatric participant required parental training and a
      second attempt. Three adult and 4 pediatric participants exhibited a noncritical
      issue while successfully completing the simulated injection. Most participants
      agreed that the injection steps were easy to follow and the PIL facilitated
      understanding on using Auvi-Q safely and effectively. CONCLUSION: The PIL and
      other labeling features were effective in communicating instructions for
      successful use of Auvi-Q. This study provided validation support for the final
      design and anticipated instructions for use of Auvi-Q.

PMID- 23548531
TI  - Perception and practice of sublingual immunotherapy among practicing allergists
      in the United States: a follow-up survey.
AB  - BACKGROUND: Limited information regarding current trends of sublingual
      immunotherapy (SLIT) use, perception, and prescribing patterns among allergists
      in the United States is available. OBJECTIVE: To obtain information about current
      allergist perception and practice of SLIT compared with 2007. METHODS: On behalf
      of the American College of Allergy, Asthma and Immunology (ACAAI) Immunotherapy
      and Diagnostics Committee, an electronic survey was sent to all practicing
      allergists of the ACAAI in August 2011. RESULTS: Fifty-nine of 519 US respondents
      (11.4%) reported experience using SLIT compared with 45 of 766 (5.9%) in 2007 (P
      < .001). Lack of Food and Drug Administration (FDA) approval was the primary
      barrier in using SLIT in the United States among 469 of 520 respondents (90.2%),
      which was increased from 471 of 763 (61.7%) in 2007 (P < .001). Among US
      respondents, 344 of 516 (66.7%) believed that SLIT was safer than subcutaneous
      immunotherapy (SCIT) compared with 554 of 755 (73.4%) in 2007 (P < .01). In
      total, 22 of 51 SLIT users (43.1%) reported SLIT efficacy equal to or even
      greater than SCIT, which was similar to 21 of 38 (55.3%) reported in 2007 (P <
      .36). CONCLUSION: Rates of SLIT use reported by US respondents have nearly
      doubled in the last 4 years, with 11.4% of US respondents reporting SLIT use.
      Because the greatest barrier to SLIT use in the United States is the lack of FDA
      approval, it is anticipated that once an FDA-approved product is available, there
      will be widespread use of SLIT in the United States. Practice guidelines, which
      include effective dosages and schedules, will be critical to the broad
      implementation of SLIT in the United States.

PMID- 23548533
TI  - A unique case of peroneus brevis/longus myositis in a patient with a STAT3
      mutation.

PMID- 23548532
TI  - Effects of 24-week add-on treatment with ciclesonide and montelukast on small
      airways inflammation in asthma.
AB  - BACKGROUND: Eosinophilic inflammation of the small airways is a key process in
      asthma that often smolders in treated patients. The long-term effects of add-on
      therapy on the persistent inflammation in the small airways remain unknown.
      OBJECTIVE: To examine the effects of add-on therapy with either ciclesonide, an
      inhaled corticosteroid with extrafine particles, or montelukast on small airway
      inflammation. METHODS: Sixty patients with stable asthma receiving inhaled
      corticosteroid treatment were enrolled in a randomized, open-label, parallel
      comparison study of 24-week add-on treatment with ciclesonide or montelukast.
      Patients were randomly assigned to 3 groups: ciclesonide (n = 19), montelukast (n
      = 22), or no add-on as controls (n = 19). At baseline and at weeks 4, 12, and 24,
      extended nitric oxide analysis; pulmonary function tests, including impulse
      oscillometry; blood eosinophil counts; and asthma control tests (ACTs) were
      performed. RESULTS: A total of 18 patients in the ciclesonide group, 19 in the
      montelukast group, and 15 in the control group completed the study and were
      analyzed. With repeated-measures analysis of variance, ciclesonide produced a
      significant decrease in alveolar nitric oxide and a significant improvement in
      ACT scores over time. Montelukast produced significant decreases in alveolar
      nitric oxide concentrations and blood eosinophil counts over time and slightly
      improved ACT scores, whereas no such changes were observed in the control group.
      Alveolar nitric oxide concentrations with ciclesonide and reactance area at low
      frequencies with montelukast produced greater improvements over time compared
      with control. CONCLUSION: Ciclesonide add-on therapy and montelukast add-on
      therapy may act differently, but both separately can improve small airway
      abnormalities and provide better asthma control. TRIAL REGISTRATION:
      umin.ac.jp/ctr Identifier: UMIN000001083.

PMID- 23548534
TI  - Errors in allergen immunotherapy administration: a systems assessment.

PMID- 23548535
TI  - Goji berry: a potential new player in latex-food syndrome.

PMID- 23548536
TI  - Stevens-Johnson syndrome: a review of 14 adult cases with one fatal outcome.

PMID- 23548537
TI  - In vivo tests with "Tahini" sauce: new allergenic source to evaluate IgE-mediated
      hypersensitivity to sesame.

PMID- 23548538
TI  - Intractable shellfish anaphylaxis: sensitization by cross-reactive substances in
      a complementary "immune stimulant" and acrylic nails.

PMID- 23548539
TI  - Adrenal suppression with fluticasone furoate.

PMID- 23548541
TI  - Allergen of the month--Wych elm.

PMID- 23548542
TI  - Development of an instrument to measure behavioral health function for work
      disability: item pool construction and factor analysis.
AB  - OBJECTIVES: To develop a broad set of claimant-reported items to assess
      behavioral health functioning relevant to the Social Security disability
      determination processes, and to evaluate the underlying structure of behavioral
      health functioning for use in development of a new functional assessment
      instrument. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: Item pools
      of behavioral health functioning were developed, refined, and field tested in a
      sample of persons applying for Social Security disability benefits (N=1015) who
      reported difficulties working because of mental or both mental and physical
      conditions. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Social Security
      Administration Behavioral Health (SSA-BH) measurement instrument. RESULTS:
      Confirmatory factor analysis (CFA) specified that a 4-factor model (self
      efficacy, mood and emotions, behavioral control, social interactions) had the
      optimal fit with the data and was also consistent with our hypothesized
      conceptual framework for characterizing behavioral health functioning. When the
      items within each of the 4 scales were tested in CFA, the fit statistics
      indicated adequate support for characterizing behavioral health as a
      unidimensional construct along these 4 distinct scales of function. CONCLUSIONS:
      This work represents a significant advance both conceptually and psychometrically
      in assessment methodologies for work-related behavioral health. The measurement
      of behavioral health functioning relevant to the context of work requires the
      assessment of multiple dimensions of behavioral health functioning. Specifically,
      we identified a 4-factor model solution that represented key domains of work
      related behavioral health functioning. These results guided the development and
      scale formation of a new SSA-BH instrument.

PMID- 23548544
TI  - Anxiety and depression associated with caregiver burden in caregivers of stroke
      survivors with spasticity.
AB  - OBJECTIVE: To investigate the relationship between anxiety/depression and
      caregiver burden in informal caregivers of stroke survivors with spasticity.
      DESIGN: Data were collected via online surveys from informal caregivers 18 years
      or older who cared for stroke survivors. SETTING: Internet-based survey.
      PARTICIPANTS: 2007 through 2009 U.S. National Health and Wellness Survey database
      or Lightspeed Research general panel respondents (N=153). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Anxiety and depression were self-reported by
      the caregiver as a physician diagnosis. Depression severity was measured by the
      Patient Health Questionnaire-9 (PHQ-9). Caregiver burden was measured by the
      Oberst Caregiving Burden Scale (OCBS) and the Bakas Caregiving Outcomes Scale
      (BCOS). Logistic regression analyses were conducted with anxiety, depression, and
      the PHQ-9 depression severity categories as a result of each caregiver burden
      scale. RESULTS: Data were analyzed for 153 informal caregivers; they were mostly
      women (70.6%) and white (78.4%), with a mean age of 51.6 years. For every 1-point
      increase in the OCBS Difficulty Scale, the odds of anxiety or depression were
      2.57 times as great (P<.001) and 1.88 times as great (P=.007), respectively. The
      odds of PHQ-9 severe depression versus all other categories combined were 2.48
      times as great (P<.001). For every 1-point decrease in the BCOS, the odds of
      anxiety or depression were 2.43 times as great (P<.001) and 2.27 times as great
      (P=.002), respectively. The odds of PHQ-9 severe depression versus all other
      categories combined were 4.55 times as great (P<.001). CONCLUSIONS: As caregiver
      burden increases, caregivers are more likely to have anxiety and depression.
      Depression severity also increases. Providing treatment to stroke survivors with
      spasticity that lessens the time and more importantly, the difficulty of
      caregiving may lead to a reduction in caregiver anxiety and depression.

PMID- 23548543
TI  - Conceptual foundation for measures of physical function and behavioral health
      function for Social Security work disability evaluation.
AB  - Physical and mental impairments represent the 2 largest health condition
      categories for which workers receive Social Security disability benefits.
      Comprehensive assessment of physical and mental impairments should include
      aspects beyond medical conditions such as a person's underlying capabilities as
      well as activity demands relevant to the context of work. The objective of this
      article is to describe the initial conceptual stages of developing new
      measurement instruments of behavioral health and physical functioning relevant
      for Social Security work disability evaluation purposes. To outline a clear
      conceptualization of the constructs to be measured, 2 content models were
      developed using structured and informal qualitative approaches. We performed a
      structured literature review focusing on work disability and incorporating
      aspects of the International Classification of Functioning, Disability and Health
      as a unifying taxonomy for framework development. Expert interviews provided
      advice and consultation to enhance face validity of the resulting content models.
      The content model for work-related behavioral health function identifies 5 major
      domains: (1) behavior control, (2) basic interactions, (3) temperament and
      personality, (4) adaptability, and (5) workplace behaviors. The content model
      describing physical functioning includes 3 domains: (1) changing and maintaining
      body position, (2) whole-body mobility, and (3) carrying, moving, and handling
      objects. These content models informed subsequent measurement properties
      including item development and measurement scale construction, and provided
      conceptual coherence guiding future empirical inquiry. The proposed measurement
      approaches show promise to comprehensively and systematically assess physical and
      behavioral health functioning relevant to work. 

PMID- 23548546
TI  - Should we screen for pulmonary hypertension at the initial evaluation of
      idiopathic pulmonary fibrosis?

PMID- 23548547
TI  - Caulerprenylols A and B, two rare antifungal prenylated para-xylenes from the
      green alga Caulerpa racemosa.
AB  - Two new prenylated para-xylenes, named caulerprenylols A (1) and B (2), were
      isolated from the green alga Caulerpa racemosa, collected from the Zhanjiang
      coastline, China. The structures of the two metabolites were elucidated on the
      basis of detailed spectroscopic analysis. This is the first report of prenylated
      para-xylenes from marine algae and from marine organisms as well. Moreover,
      caulerprenylol B (2) is also characterized by an uncommon indane ring system. In
      in vitro bioassays, the new compounds exhibited a broad spectrum of antifungal
      activity against Candida glabrata (537), Trichophyton rubrum (Cmccftla), and
      Cryptococcus neoformans (32609) with MIC80 values between 4 and 64 MUg/mL when
      compared to amphotericin B (MIC80 values of 2.0, 1.0, and 4.0 MUg/mL,
      respectively) as a positive control and showed no growth inhibition activity
      against the tumor cells HL60 and A549.

PMID- 23548545
TI  - Does exercise tolerance testing at 60 days poststroke predict rehabilitation
      performance?
AB  - OBJECTIVE: To assess the relationship between exercise tolerance test (ETT)
      performance at 6 weeks poststroke and subsequent performance in a treadmill and
      overground locomotor training program (LTP). DESIGN: Prospective cohort study.
      SETTING: Exercise testing laboratory in either a primary care hospital or
      outpatient clinic. PARTICIPANTS: Community-dwelling individuals (N=469), 54.9+/
      19.0 days poststroke, enrolled in the Locomotor Experience Applied Post-Stroke
      randomized controlled trial. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: For participants randomly assigned to LTP, the number of sessions
      needed to attain the training goal of 20 minutes of treadmill stepping was
      determined. Regression analyses determined the contribution of ETT performance
      (cycling duration), age, and 6-minute walk test (6MWT) distance to attainment of
      the stepping duration goal. RESULTS: Age, 6MWT, and ETT performance individually
      accounted for 10.74%, 10.82%, and 10.76%, respectively, of the variance in the
      number of sessions needed to attain 20 minutes of stepping. When age and 6MWT
      were included in the model, the additional contribution of ETT performance was
      rendered nonsignificant (P=.150). CONCLUSIONS: To the extent that ETT performance
      can be viewed as a measure of cardiovascular fitness rather than neurologic
      impairment, cardiovascular fitness at the time of the ETT did not make a
      significant unique contribution to the number of sessions needed to achieve 20
      minutes of stepping. The 6MWT, which involves less intensive exercise than the
      ETT and therefore is likely to be predominantly affected by neurologic impairment
      and muscular condition, appeared to account for as much variance as the ETT.

PMID- 23548548
TI  - Memory awareness profiles differentiate mild cognitive impairment from early
      stage dementia: evidence from assessments of performance monitoring and
      evaluative judgement.
AB  - BACKGROUND: Measures of memory awareness based on evaluative judgement and
      performance monitoring are often regarded as equivalent, but the Levels of
      Awareness Framework suggests they reflect different awareness phenomena.
      Examination of memory awareness among groups with differing degrees of impairment
      provides a test of this proposition. METHOD: Ninety-nine people with dementia
      (PwD), 30 people with mild cognitive impairment (PwMCI), and their relatives
      completed isomorphic performance monitoring and evaluative judgement measures of
      memory awareness and were followed up at 12 and (PwD only) 20 months. In addition
      to the resulting awareness indices, comparative accuracy scores were calculated
      using the relatives' data to establish whether any inaccuracy was specific to
      self-ratings. RESULTS: When making evaluative judgements about their memory in
      general, both PwD and PwMCI tended to overestimate their own functioning relative
      to informant ratings made by relatives. When monitoring performance on memory
      tests, PwD again overestimated performance relative to test scores, but PwMCI
      were much more accurate. Comparative accuracy scores indicated that, unlike PwD,
      PwMCI do not show a specific inaccuracy in self-related appraisals. CONCLUSIONS:
      The results support the proposition that awareness indices at the levels of
      evaluative judgement and performance monitoring should be regarded as reflecting
      distinct awareness phenomena.

PMID- 23548549
TI  - The view from the road: the contribution of on-road glance-monitoring
      technologies to understanding driver behavior.
AB  - Using glance-monitoring technologies for on-road studies is an excellent way to
      investigate driver behaviors in an ecologically valid setting. Recent advances in
      glance-monitoring technologies have made it possible to conduct on-road studies
      of drivers' glance behavior that heretofore were simply not possible. Yet it is
      not always easy to determine which glance-monitoring technology to use for a
      particular application. Here, we first identify the generic capabilities of the
      various glance-monitoring technologies. We then describe how particular glance
      monitoring technologies have been used in the field to (a) identify the skill
      deficiencies of novice and older drivers, (b) evaluate the effectiveness of
      training programs that are designed to reduce deficits in these skills, and (c)
      address interface issues both inside (e.g., collision warning systems) and
      outside (e.g., yield markings) the vehicle. The limitations and advantages of on
      road eye-tracking and the associated glance-monitoring technologies are
      identified throughout. A comparison, where possible, is made between the results
      of on-road eye-tracking studies of drivers' behaviors and the results of those
      studies conducted in the laboratory. Overall, the use of appropriate on-road
      glance-monitoring technologies has greatly enhanced our theoretical understanding
      of why drivers behave the way they do, and this knowledge has paved the way for
      significant improvements in road user safety. 

PMID- 23548550
TI  - Administration of yellow fever vaccine in patients with egg allergy.
AB  - BACKGROUND: The population of large parts of Africa, South America and travellers
      to these areas are at risk of yellow fever (YF) with a 50% mortality risk. Yellow
      fever vaccine (YFV) propagated in hens' eggs confers protection in 95% of the
      vaccinated. The rate of anaphylaxis for YFV ranges from 0.42 to 1.8/100,000 doses
      with most cases considered to be due to egg allergy. Egg allergy is a
      contraindication for the YFV. Nevertheless, the potential fatal sequelae from YF
      give the incentive to protect everyone at risk irrespective of their allergic
      status. METHODS: Six subjects who had had a recent reaction to egg and who were
      travelling to endemic areas (3 adults and 3 children) underwent skin prick tests
      (SPT) with undiluted YFV and egg extract. Intradermal tests for YFV were
      undertaken at a 1:10 dilution. In 4 egg-allergic patients with a positive SPT to
      YFV, a 7-step desensitization protocol was used. A 2-step (10 + 90%) protocol was
      used in the 2 subjects with a negative YFV SPT. Premedication was not
      administered. RESULTS: All 6 patients were successfully vaccinated. Four patients
      completed desensitization: 1 developed mild local erythema at the injection site,
      1 had fleeting generalized urticaria with local erythema/angioedema and 2 did not
      experience any adverse reactions. Patients who received YFV in 2 steps developed
      no adverse reactions. CONCLUSIONS: We describe the successful administration of
      YFV in 6 egg-allergic patients. The Cambridge Allergy 7-step protocol allows for
      its safe administration in patients with positive SPT to YFV. A 2-step protocol
      can be used in patients with negative YFV SPT.

PMID- 23548551
TI  - Inhibition of miR-21 induces biological and behavioral alterations in diffuse
      large B-cell lymphoma.
AB  - MicroRNA-21 (miR-21) has been ascribed a key role in many cellular processes,
      e.g. tumorigenesis via inhibition of target gene expression. However, its role in
      diffuse large B-cell lymphoma (DLBCL) is still unclear, and there are no in-depth
      studies on the relationship between miR-21 and the cellular phenotype of DLBCL.
      In this study, we investigated the expression and role of miR-21 in the
      regulation of cell biological processes in DLBCL. Firstly, miR-21 expression was
      evaluated in three DLBCL cell lines by real-time quantitative reverse
      transcription (qRT) polymerase chain reaction (PCR). Then, to determine the
      possible role of miR-21 in the biological and behavioral characteristics of
      DLBCL, we performed miR-21 knockdown by transfection with anti-miR-21. In
      addition, PDCD4 and PTEN were assessed by luciferase reporter assay, qRT-PCR, and
      Western blot. Our study revealed that miR-21 was significantly upregulated in
      activated B-cell-like DLBCL cells compared to germinal center-like DLBCL cells.
      We demonstrated that inhibition of miR-21 induced suppression of proliferation
      and invasion, as well as increased apoptosis in DLBCL. Moreover, knockdown of miR
      21 increased PDCD4 and PTEN expression at the protein level but not at the mRNA
      level. In conclusion, miR-21 can regulate proliferation, invasion, and apoptosis,
      and thus it has a potential therapeutic application in DLBCL. 

PMID- 23548552
TI  - Tracing the spread of hepatitis C virus in Turkey: a phylogenetic analysis.
AB  - BACKGROUND/AIMS: Molecular epidemiology of hepatitis C virus (HCV) shows that HCV
      genotypes are unique with respect to their nucleotide sequence, geographical
      distribution and clinical relationship. METHODS: In this study we enrolled 67 HCV
      infected individuals with various stages of liver disease from four geographical
      regions of Turkey. A partial NS5B region of the HCV genome was sequenced and
      subjected to phylogenetic analysis to determine the circulating HCV genotypes and
      subtypes. RESULTS: The results showed that HCV genotype 1 (subtype1b) is the main
      genetic variant of HCV in Turkey but did not reveal any Turkish indigenous
      phylogenetic cluster. Phylogenetic analysis showed that Turkish strains have
      their closest matches from both Asia (Japan) and Europe/USA. CONCLUSIONS: In view
      of Turkey's geographic position, HCV-1b transmission from Europe is not
      exceptional. This study could not establish a clear role of other HCV genotypes
      prevalent in neighboring Asian countries in Turkey's HCV transmission, which
      would need to be confirmed by further regional epidemiological studies.

PMID- 23548553
TI  - First report of a small supernumerary der(8;14) marker chromosome.
AB  - Small supernumerary marker chromosomes (sSMC) are structurally abnormal
      chromosomes, generally equal in size or smaller than a chromosome 20 of the same
      metaphase spread. Most of them are unexpectedly detected in routine karyotype
      analyses, and it is usually not easy to correlate them with a specific clinical
      picture. A small group of sSMCs is derived from more than one chromosome, called
      complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived
      from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation
      dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based
      array, and fluorescence in situ hybridization (FISH) were performed to
      investigate its origin. Array and FISH analyses revealed a
      der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features
      commonly found in patients with partial duplication or triplication of 8p and
      14q. This is the first report describing a patient with a congenital
      der(14)t(8;14)(p23.2;q22.1)dn sSMC.

PMID- 23548554
TI  - Changes in left ventricular diastolic function during hemodialysis sessions.
AB  - BACKGROUND: Left ventricular diastolic dysfunction is common in hemodialysis
      patients and is associated with worse outcome. Previous studies have shown that
      diastolic function worsens from pre- to post-dialysis session, but this has not
      been studied during hemodialysis. We studied the evolution of diastolic function
      parameters early and late during hemodialysis. STUDY DESIGN: Observational study.
      SETTING & PARTICIPANTS: 109 hemodialysis patients on a thrice-weekly dialysis
      schedule with a mean age of 62.5 +/- 15.6 (SD) years were studied between March
      2009 and March 2010. PREDICTOR: Hemodialysis with constant ultrafiltration rate
      and dialysate conductivity. OUTCOMES: Changes in diastolic function parameters.
      MEASUREMENTS: Mitral early inflow (E) and tissue Doppler early diastolic velocity
      (mean e') were evaluated by echocardiography predialysis, at 60 and 180 minutes
      intradialysis, and postdialysis. Relative blood volume changes were calculated
      from changes in hematocrit. RESULTS: Predialysis E and mean e' were 0.93 +/- 0.24
      m/s and 6.6 +/- 2.1 cm/s, respectively. E and mean e' values decreased
      significantly during hemodialysis (P < 0.001). The steepest change occurred at 60
      minutes intradialysis (E, -21.4% +/- 17.6% and -30.5% +/- 19.2% at 60 and 180
      minutes, respectively; mean e', -16.0% +/- 18.6% and -19.5% +/- 21.8% at 60 and
      180 minutes, respectively). At 60 minutes intradialysis, changes in relative
      blood volume and brain natriuretic peptide level were associated significantly
      with the change in E but not with the change in mean e'. LIMITATIONS: Changes in
      relative blood volume may not fully reflect central blood volume changes and do
      not capture the effect of blood loss to the extracorporal circuit. Left atrial
      volume was not measured. CONCLUSIONS: Left ventricular diastolic function worsens
      early during a hemodialysis session. The decrease in mean e' at 60 minutes
      intradialysis was unrelated to changes in relative blood volume. Although this
      finding does not exclude a role of hypovolemia because of the limitations of the
      measurement of relative blood volume, it raises the possibility that non-volume
      related mechanisms are involved in the early decrease in mean e' during
      hemodialysis.

PMID- 23548555
TI  - Oxalate nephropathy and intravenous vitamin C.
AB  - Oxalate nephropathy is a rare condition characterized by extensive calcium
      oxalate deposition in the renal tubules, resulting in kidney injury. There are
      primary forms of the disease that arise from genetic mutation causing
      overproduction of oxalate. More commonly, this condition is seen as a secondary
      phenomenon. The clinical presentation is nonspecific, with acute kidney injury
      and normal serologic study results. The characteristic finding on kidney biopsy
      is the presence of acute tubular injury associated with polarizable crystals in
      the tubular lumen and epithelial cytoplasm. We present a case of acute oxalate
      nephropathy in a patient with underlying systemic lupus erythematosus who
      recently received intravenous vitamin C.

PMID- 23548556
TI  - Hepatitis C-associated cryoglobulinemic glomerulonephritis with crystalline
      deposits.
AB  - Infection with hepatitis C virus has been associated with a number of
      extrahepatic manifestations, including kidney disease. Of the glomerular
      pathologic states described with hepatitis C virus infection, cryoglobulinemic
      glomerulonephritis is the most prevalent. On kidney biopsy, cryoglobulinemic
      glomerulonephritis has a variable appearance, with a membranoproliferative
      pattern of injury as the most common light microscopic finding.
      Ultrastructurally, curved and paired microtubules are the most characteristic
      finding, but these also can be variable. We present a case of cryoglobulinemic
      glomerulonephritis with distinct and highly unusual ultrastructural findings. 

PMID- 23548557
TI  - Diuretics or ultrafiltration for acute decompensated heart failure and
      cardiorenal syndrome?

PMID- 23548558
TI  - Immune complex disease with a lupus-like pattern of deposition in an antinuclear
      antibody-negative patient.
AB  - Immune complex-mediated glomerulonephritis can be caused by a multitude of
      disease processes and may manifest in a variety of histologic patterns. Lupus
      nephritis is an immune complex disease, the diagnosis of which requires that the
      affected patient have systemic lupus erythematosus (SLE). In the absence of SLE,
      the finding of glomerulonephritis with certain patterns of immune complex
      deposition characteristic of lupus nephritis has been referred to as lupus-like
      glomerulonephritis. Immunoglobulin G (IgG), IgA, IgM, complement C3, and C1q
      deposition in glomerular immune deposits is one such pattern. We report a case of
      immune complex disease in a primarily membranous distribution with mesangial,
      subendothelial, and tubular basement membrane deposits with IgG, IgA, IgM, C3,
      and C1q deposition in a patient with proteinuria, photosensitive dermatitis, and
      a positive lupus anticoagulant test. The patient had 3 of the clinical criteria
      for SLE, thus failing to meet the diagnosis based on the American College of
      Rheumatology definition. In this case, a diagnosis of lupus-like
      glomerulonephritis was made after other causes of membranous glomerulopathy were
      excluded. This teaching case highlights the broad differential diagnosis of this
      pattern of injury and reviews similar cases in the literature.

PMID- 23548559
TI  - Gender-dimorphic regulation of skeletal muscle proteins in streptozotocin-induced
      diabetic rats.
AB  - BACKGROUND: Despite the fact that sexual differences increase diabetic risk and
      contribute to the need for gender-specific care, there remain contradictory
      results as to whether or not sexual dimorphism increases susceptibility to the
      development of type 1 diabetes mellitus. METHODS: To examine gender-dimorphic
      regulation of skeletal muscle proteins between healthy control and STZ-induced
      diabetic rats of both genders, we performed differential proteome analysis using
      two-dimensional electrophoresis combined with mass spectrometry. RESULTS: Animal
      experiments revealed that STZ treatment rendered female rats more susceptible to
      induction of diabetes than their male littermates with significantly lower plasma
      insulin levels due to hormonal regulation. Proteomic analysis of skeletal muscle
      identified a total of 21 proteins showing gender-dimorphic differential
      expression patterns between healthy controls and diabetic rats. Most
      interestingly, gender-specific proteome comparison showed that male and female
      rats displayed differential regulation of proteins involved in muscle
      contraction, carbohydrate, and lipid metabolism, as well as oxidative
      phosphorylation and cellular stress. CONCLUSION: The current proteomic study
      revealed that impaired protein regulation was more prominent in the muscle tissue
      of female diabetic rats, which were more susceptible to STZ-induced diabetes. We
      expect that the present proteomic data can provide valuable information for
      evidence-based gender-specific treatment of diabetes.

PMID- 23548560
TI  - Inter-individual variation and temperature-dependent antipredator behavior in the
      snake Tomodon dorsatus (Dipsadidae).
AB  - Although many studies assessed the influence of temperature on the behavior of
      ectotermic vertebrates, little attention has been given to interindividual
      variation in the defensive responses of reptiles. In the present study we
      investigated the defensive behavior of the snake Tomodon dorsatus, in order to
      test the hypotheses that (1) individuals differ in their antipredator behavior
      consistently with the concept of behavioral syndromes, (2) temperature influences
      the defensive behavior, and (3) these two factors interact with each other. There
      was significant interindividual variation in defensive behavior, as well as
      consistently aggressive, passive or evasive behaviors. Temperature influenced
      aggressiveness, which was slightly higher when body temperature was lower, but
      this trend was only evident in animals with aggressive disposition. Our results
      corroborate the hypothesis of interaction between individuality of behavior and
      temperature-dependent defensive behavior in T. dorsatus. These results, together
      with results from previous studies, suggest that the evolution of temperature
      dependent defensive behavior differs among lineages of ectothermic tetrapods.
      This article is part of a Special Issue entitled: insert SI title. 

PMID- 23548561
TI  - Comparison between bilateral cochlear implants and Neurelec Digisonic((r)) SP
      Binaural cochlear implant: speech perception, sound localization and patient self
      assessment.
AB  - An alternative to bilateral cochlear implantation is offered by the Neurelec
      Digisonic((r)) SP Binaural cochlear implant, which allows stimulation of both
      cochleae within a single device. The purpose of this prospective study was to
      compare a group of Neurelec Digisonic((r)) SP Binaural implant users (denoted
      BINAURAL group, n = 7) with a group of bilateral adult cochlear implant users
      (denoted BILATERAL group, n = 6) in terms of speech perception, sound
      localization, and self-assessment of health status and hearing disability. Speech
      perception was assessed using word recognition at 60 dB SPL in quiet and in a
      'cocktail party' noise delivered through five loudspeakers in the hemi-sound
      field facing the patient (signal-to-noise ratio = +10 dB). The sound localization
      task was to determine the source of a sound stimulus among five speakers
      positioned between -90 degrees  and +90 degrees  from midline. Change in health
      status was assessed using the Glasgow Benefit Inventory and hearing disability
      was evaluated with the Abbreviated Profile of Hearing Aid Benefit. Speech
      perception was not statistically different between the two groups, even though
      there was a trend in favor of the BINAURAL group (mean percent word recognition
      in the BINAURAL and BILATERAL groups: 70 vs. 56.7% in quiet, 55.7 vs. 43.3% in
      noise). There was also no significant difference with regard to performance in
      sound localization and self-assessment of health status and hearing disability.
      On the basis of the BINAURAL group's performance in hearing tasks involving the
      detection of interaural differences, implantation with the Neurelec
      Digisonic((r)) SP Binaural implant may be considered to restore effective
      binaural hearing. Based on these first comparative results, this device seems to
      provide benefits similar to those of traditional bilateral cochlear implantation,
      with a new approach to stimulate both auditory nerves.

PMID- 23548562
TI  - Electromagnetic characterization of an MR volume coil with multilayered
      cylindrical load using a 2-D analytical approach.
AB  - We present an analytical method for the analysis of Radio Frequency (RF) volume
      coils for Magnetic Resonance Imaging (MRI), using a 2-D full wave solution with
      loading by multilayered cylinders. This allows the characterization of radio
      frequency E, H, B1, B1(+) fields. Comparisons are provided with experimental data
      obtained at 7.0 T. The procedure permits us to clearly separate the solution to
      single line source problem (which we call the primordial solution) and the
      composite solution (i.e. full coil, i.e. the summations of primordial solutions
      according to the resonator drive configuration). The capability of separating the
      primordial solution and the composite one is fundamental for a thorough analysis
      of the phenomena of dielectric resonance, and of standing wave and multi-source
      interference. We show that dielectric resonance can be identified only by looking
      at the electromagnetic field from a single line source.

PMID- 23548563
TI  - Estimation of pore size distribution using concentric double pulsed-field
      gradient NMR.
AB  - Estimation of pore size distribution of well calibrated phantoms using NMR is
      demonstrated here for the first time. Porous materials are a central constituent
      in fields as diverse as biology, geology, and oil drilling. Noninvasive
      characterization of monodisperse porous samples using conventional pulsed-field
      gradient (PFG) NMR is a well-established method. However, estimation of pore size
      distribution of heterogeneous polydisperse systems, which comprise most of the
      materials found in nature, remains extremely challenging. Concentric double
      pulsed-field gradient (CDPFG) is a 2-D technique where both q (the amplitude of
      the diffusion gradient) and phi (the relative angle between the gradient pairs)
      are varied. A recent prediction indicates this method should produce a more
      accurate and robust estimation of pore size distribution than its conventional 1
      D versions. Five well defined size distribution phantoms, consisting of 1-5
      different pore sizes in the range of 5-25 MUm were used. The estimated pore size
      distributions were all in good agreement with the known theoretical size
      distributions, and were obtained without any a priori assumption on the size
      distribution model. These findings support that in addition to its theoretical
      benefits, the CDPFG method is experimentally reliable. Furthermore, by adding the
      angle parameter, sensitivity to small compartment sizes is increased without the
      use of strong gradients, thus making CDPFG safe for biological applications.

PMID- 23548564
TI  - Partial nitrification and anammox process: a method for high strength
      optoelectronic industrial wastewater treatment.
AB  - Completely autotrophic nitrogen removal over nitrite (CANON) process was employed
      in an 18 L sequencing batch reactor (SBR) for treatment of optoelectronic
      industrial wastewater containing high strength ammonium nitrogen (3712 +/- 120 mg
      NH4(+) - N L(-1)). About 89% of total nitrogen and 98% of NH4(+) - N removal
      efficiencies were observed at the loading rate of 909 g N m(-3) d(-1) and the HRT
      of 4 d. A profound variation in the performance of CANON process was experienced
      at high DO exposure (above 1 mg L(-1)) and high nitrite concentration (above 100
      mg L(-1)). Inhibition due to high DO exposure was found to be reversible
      phenomenon whereas the synergistic inhibition of nitrite, free ammonia and free
      nitrous acid was irreversible. The fluctuation of reactor temperature between 17
      and 37  degrees C did not affect the performance of CANON system. The CANON
      process was stably controlled at high nitrogen loading rate for more than one
      month. The co-existence of aerobic and anaerobic ammonium oxidizing bacteria in
      the reactor was detected by The PCR analysis. About 5 fold increase in amount of
      anammox bacteria over a period of 258 days was confirmed from the results of qPCR
      on day 487.

PMID- 23548565
TI  - The zerovalent iron nanoparticle causes higher developmental toxicity than its
      oxidation products in early life stages of medaka fish.
AB  - Nanoscale zerovalent iron (nZVI)-mediated oxidation reaction is increasingly
      being used for enhanced treatment of water or wastewater processes; however, the
      fate and eco-toxicological effects of nZVI in the surface aquifer remain unclear.
      We investigated bioaccumulation and lethal-to-sublethal toxic effects on early
      life development of Japanese medaka (Oryzias latipes) with 7-day exposure to 25
      200 mg/L of well-characterized solutions containing carboxymethyl cellulose (CMC)
      stabilized nZVI (CMC-nZVI), nanoscale iron oxide (nFe3O4) or ferrous ion
      [Fe(II)aq]. The CMC-nZVI solution had the greatest acute mortality and
      developmental toxic effects in embryos, with lesser and the least effects with
      Fe(II)aq and nFe3O4. The toxicity of CMC-nZVI was ascribed to its high reactivity
      in the oxygenic solution, which led to a combination of hypoxia and production of
      reactive oxygen species (ROS) and Fe(II)aq. nFe3O4 (50-100 mg/L) was more
      bioavailable to embryos and bioaccmulative in hatchlings than suspended CMC-nZVI.
      The antioxidant balance was differentially altered by induced intracellular ROS
      in hatchlings with all 3 iron species. We revealed causal toxic effects of nZVI
      and its oxidized products in early life stages of medaka fish using different
      organizational levels of biomarker assays. The toxicity results implicate a
      potential eco-toxicological impact of nZVI on the aquatic environment.

PMID- 23548566
TI  - Contamination of Canadian private drinking water sources with antimicrobial
      resistant Escherichia coli.
AB  - BACKGROUND: Surface and ground water across the world, including North America,
      is contaminated with bacteria resistant to antibiotics. The consumption of water
      contaminated with antimicrobial resistant Escherichia coli (E. coli) has been
      associated with the carriage of resistant E. coli in people who drink it.
      OBJECTIVES: To describe the proportion of drinking water samples submitted from
      private sources for bacteriological testing that were contaminated with E. coli
      resistant to antibiotics and to determine risk factors for the contamination of
      these water sources with resistant and multi-class resistant E. coli. METHODS:
      Water samples submitted for bacteriological testing in Ontario and Alberta Canada
      were tested for E. coli contamination, with a portion of the positive isolates
      tested for antimicrobial resistance. Households were invited to complete
      questionnaires to determine putative risk factors for well contamination.
      RESULTS: Using multinomial logistic regression, the risk of contamination with E.
      coli resistant to one or two classes of antibiotics compared to susceptible E.
      coli was higher for shore wells than drilled wells (odds ratio [OR] 2.8) and
      higher for farms housing chickens or turkeys (OR 3.0) than properties without
      poultry. The risk of contamination with multi-class resistant E. coli (3 or more
      classes) was higher if the properties housed swine (OR 5.5) or cattle (OR 2.2)
      than properties without these livestock and higher if the wells were located in
      gravel (OR 2.4) or clay (OR 2.1) than in loam. CONCLUSIONS: Housing livestock on
      the property, using a shore well, and having a well located in gravel or clay
      soil increases the risk of having antimicrobial resistant E. coli in E. coli
      contaminated wells. To reduce the incidence of water borne disease and the
      transmission of antimicrobial resistant bacteria, owners of private wells need to
      take measures to prevent contamination of their drinking water, routinely test
      their wells for contamination, and use treatments that eliminate bacteria.

PMID- 23548567
TI  - Identifying early events of gene expression in breast cancer with systems biology
      phylogenetics.
AB  - Advanced omics technologies such as deep sequencing and spectral karyotyping are
      revealing more of cancer heterogeneity at the genetic, genomic, gene expression,
      epigenetic, proteomic, and metabolomic levels. With this increasing body of
      emerging data, the task of data analysis becomes critical for mining and modeling
      to better understand the relevant underlying biological processes. However, the
      multiple levels of heterogeneity evident within and among populations, healthy
      and diseased, complicate the mining and interpretation of biological data,
      especially when dealing with hundreds to tens of thousands of variables.
      Heterogeneity occurs in many diseases, such as cancers, autism, macular
      degeneration, and others. In cancer, heterogeneity has hampered the search for
      validated biomarkers for early detection, and it has complicated the task of
      finding clonal (driver) and nonclonal (nonexpanded or passenger) aberrations. We
      show that subtyping of cancer (classification of specimens) should be an a priori
      step to the identification of early events of cancers. Studying early events in
      oncogenesis can be done on histologically normal tissues from diseased
      individuals (HNTDI), since they most likely have been exposed to the same
      mutagenic insults that caused the cancer in their neighboring tissues. Polarity
      assessment of HNTDI data variables by using healthy specimens as outgroup(s),
      followed by the application of parsimony phylogenetic analysis, produces a
      hierarchical classification of specimens that reveals the early events of the
      disease ontogeny within its subtypes as shared derived changes (abnormal changes)
      or synapomorphies in phylogenetic terminology.

PMID- 23548568
TI  - Growth in small-for-gestational-age preterm-born children from 0 to 4 years: the
      role of both prematurity and SGA status.
AB  - BACKGROUND: Fullterm small-for-gestational-age children (SGAs) are known for
      their ability to catch up on growth. Nevertheless, increased risk of growth
      restriction remains. Evidence on preterm SGA children's growth is lacking.
      OBJECTIVE: To determine absolute gains in height and weight, relative growth, and
      growth restriction in preterm SGAs from 0 to 4 years and how prematurity and SGA
      status affect these measures. DESIGN/METHODS: Community-based cohort study, n =
      1,648 preterm-born (gestational age <36 weeks, 57 SGA) and 605 term-born (12
      SGA). We defined SGA as a birth weight less than -2 SD (P 2.3) compared to
      counterparts matched for gestational age. Height, weight, and head circumference
      were obtained from medical records and translated to z-scores. We defined growth
      restriction as height or weight less than -2 SD compared to fullterm appropriate
      for-gestational-age children (AGAs). RESULTS: Absolute height and weight gains
      were similar, but the relative growth of preterms and fullterms differed. Preterm
      AGAs and fullterm SGAs, although not reaching it, caught up towards the fullterm
      AGA median (z-scores at 4 years: -0.3 to -1.0). By contrast, preterm SGA
      children's z-scores were still -1.4 to -1.7. Head circumference growth was less
      affected by prematurity and SGA birth (z-scores at 1 year: 0.1 to -0.7). Catch-up
      growth mainly took place during infancy. 30-39% of all preterm SGAs showed growth
      restriction at 4 years. CONCLUSIONS: Growth in preterm SGAs is affected
      considerably by the joint effects of preterm birth and SGA status, resulting in a
      high proportion of growth restriction.

PMID- 23548569
TI  - Development and validation of multiplex real-time PCR assay for noninvasive
      prenatal assessment of fetal RhD status and fetal sex in maternal plasma.
AB  - OBJECTIVE: Noninvasive prenatal detection of RhD status and fetal sex is becoming
      part of daily practice in clinical laboratories. We evaluated a high throughput
      procedure for automated DNA extraction and developed a multiplex real-time PCR
      (rt-PCR) for the simultaneous detection of three fetal loci in a single reaction
      to assess fetal sex and RhD status in maternal plasma. METHODS: An automated DNA
      extraction method was evaluated together with a new multiplex rt-PCR assay for
      the simultaneous detection of exons 5 and 7 of the RHD gene together with the Y
      chromosome marker DYS14 in maternal plasma. The test was evaluated on 60 samples
      of known fetal genotype obtained from RhD-negative pregnant women before being
      applied prospectively on 158 consecutive clinical cases. Results were compared
      with newborn phenotypes. RESULTS: Automated DNA extraction allowed successful
      analysis of all samples. DYS14 was detected in 118 cases (male fetuses) and both
      RHD exon 5 and 7 were detected in 148 samples. In 70 samples neither RHD exon 5
      nor RHD exon 7 were detected (RhD-negative fetuses). Absence of all three
      sequences (female RhD-negative fetuses) was assessed in 33 samples. All prenatal
      results were in concordance with postnatal RhD status and fetal sex without false
      positive or -negative results. CONCLUSION: The automated DNA extraction
      procedure coupled with a novel multiplex rt-PCR assay proved accurate, efficient
      and reliable allowing rapid and high throughput noninvasive determination of
      fetal sex and RhD status in clinical samples.

PMID- 23548570
TI  - Uraemic pruritus: relief of itching by gabapentin and pregabalin.
AB  - BACKGROUND: Pruritus (skin irritation or itching) is common in patients with
      chronic kidney disease (CKD) stages 4 and 5. It is associated with disrupted
      sleep, reduced quality of life, depression and increased mortality. A video of a
      patient describing the symptoms is at vimeo.com/49458473. METHODS: We used
      gabapentin or pregabalin in 71 consecutive patients, 82% male. 25 had CKD stage 4
      or 5, median eGFR = 17, range 9-30; 40 were on haemodialysis; 6 on peritoneal
      dialysis. Median itch severity score out of 10 = 8, range 6-10; median duration
      of itching = 6 months, range 0.5-240. Serum calcium <=2.60 mmol/l (<=10.4 mg/dl)
      in 87% patients, phosphate <=1.8 mmol/l (<=5.6 mg/dl) in 75%. 63% had used
      antihistamines and not gained relief. Starting dose of gabapentin 100 mg after
      dialysis or daily. Patients intolerant of gabapentin were offered pregabalin,
      starting dose 25 mg after dialysis or daily. RESULTS: Gabapentin relieved itching
      in 47 patients (66%). A video of a patient describing the effect is at
      vimeo.com/49455976. 26 patients (37%) suffered side effects from gabapentin. Of
      21 patients who stopped gabapentin due to side effects, 16 started pregabalin.
      Pregabalin relieved itching in 13 patients (81%). In total, gabapentin or
      pregabalin relieved itching in 60 patients (85%), median follow-up 2 months
      (range 1-8 months). Median itch severity out of 10 reduced from 8 to 1.
      CONCLUSIONS: Gabapentin or pregabalin relieved itching in 85% of 71 consecutively
      treated CKD patients. Patients should be advised about side effects and the drug
      initiated at a low dose. Patients intolerant of gabapentin may tolerate
      pregabalin.

PMID- 23548571
TI  - Poly(ADP-ribosylation) regulates chromatin organization through histone H3
      modification and DNA methylation of the first cell cycle of mouse embryos.
AB  - We examined the roles of poly(ADP-ribosylation) in chromatin remodeling during
      the first cell cycle of mouse embryos. Drug-based inhibition of poly(ADP
      ribosylation) by a PARP inhibitor, PJ-34, revealed up-regulation of dimethylation
      of histone H3 at lysine 4 in male pronuclei and down-regulation of dimethylation
      of histone H3 at lysine 9 (H3K9) and lysine 27 (H3K27). Association of poly(ADP
      ribosylation) with histone modification was suggested to be supported by the
      interaction of Suz12, a histone methyltransferase in the polycomb complex, with
      Parp1. PARP activity was suggested to be required for a proper localization and
      maintenance of Suz12 on chromosomes. Notably, DNA methylation level of female
      pronuclei in one-cell embryos was robustly decreased by PJ-34. Electron
      microscopic analysis showed a frequent appearance of unusual electron-dense areas
      within the female pronuclei, implying the disorganized and hypercondensed
      chromatin ultrastructure. These results show that poly(ADP-ribosylation) is
      important for the integrity of non-equivalent epigenetic dynamics of pronuclei
      during the first cell cycle of mouse embryos.

PMID- 23548572
TI  - N-Glycosylation modulates the membrane sub-domain distribution and activity of
      glucose transporter 2 in pancreatic beta cells.
AB  - The glucose transporter isoform, GLUT2, -mediated glucose sensing is essential
      for maintaining normal glucose-stimulated insulin secretion in pancreatic beta
      cells. We previously reported that GnT-IVa glycosyltransferase is required for
      the production of an N-glycan structure that acts as a ligand for galectins to
      form the glycan-galectin lattice that maintains the stable cell surface
      expression of GLUT2, and cellular glucose transport activity, although the
      functional relevance of the N-glycosylation of GLUT2 to its membrane sub-domain
      distribution is not fully understood. In the present study, we demonstrated that
      disruption of the GLUT2 N-glycan-galectin lattice by the genetic inactivation of
      GnT-IVa, or by treatment of pancreatic beta cells with competitive glycan
      mimetics, induced the re-distribution of GLUT2 into the lipid-raft microdomain.
      This subsequently resulted in the binding of Stomatin to GLUT2 and an attenuation
      of cellular glucose transport activity. Moreover, disruption of the lipid-raft
      microdomain by treatment with methyl-beta-cyclodextrin caused the GLUT2 to be
      released from lipid-rafts and reactivation of the cellular glucose transport
      activity in GnT-IVa deficient beta cells. These results indicate that the
      membrane sub-domain distribution of GLUT2 is associated with the glucose
      transport activity of beta cells, in which the GnT-IVa-dependent formation of the
      N-glycan-galectin lattice plays an important role. This provides a novel
      pathophysiological insight into the mechanism of beta cell failure in the
      pathogenesis of type 2 diabetes.

PMID- 23548573
TI  - UV-dependent production of 25-hydroxyvitamin D2 in the recombinant yeast cells
      expressing human CYP2R1.
AB  - CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We
      have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal
      its enzymatic properties. In this study, we examined production of 25
      hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1.
      When vitamin D3 or vitamin D2 was added to the cell suspension of CYP2R1
      expressing yeast cells in a buffer containing glucose and beta-cyclodextrin, the
      vitamins were converted into their 25-hydroxylated products. Next, we irradiated
      the cell suspension with UVB and incubated at 37  degrees C. Surprisingly, the 25
      hydroxy vitamin D2 was produced without additional vitamin D2. Endogenous
      ergosterol was likely converted into vitamin D2 by UV irradiation and thermal
      isomerization, and then the resulting vitamin D2 was converted to 25
      hydroxyvitamin D2 by CYP2R1. This novel method for producing 25-hydroxyvitamin D2
      without a substrate could be useful for practical purposes.

PMID- 23548574
TI  - Contributions of maternal and infant factors to infant responding to the still
      face paradigm: a longitudinal study.
AB  - Early mother-infant interactions are characterised by periods of synchronous
      interaction that are interrupted by periods of mismatch; the experience of such
      mismatches and their subsequent repair is held to facilitate the development of
      infant self-regulatory capacities (Tronick, Als, Adamson, Wise, & Brazelton,
      1978). Infant responding to such interactive challenge is assumed to be a
      function of both maternal behaviour and pre-existing infant characteristics.
      However, the latter has received relatively little attention. In a prospective
      longitudinal study of a sample comprising high and low adversity dyads (n=122),
      we examined the contributions of both maternal sensitivity and neonatal
      irritability to infant behavioural and physiological responding to the
      interactive challenge of the Still Face paradigm. Results indicated that higher
      levels of maternal sensitivity were associated with more regulated infant
      behaviour during the Still Face paradigm. Neonatal irritability also predicted
      poorer behavioural and heart rate recovery following the Still Face challenge.
      Furthermore, there was an interaction such that irritable infants with
      insensitive mothers showed the worst behavioural outcomes. The findings highlight
      the importance of the interplay between maternal and infant characteristics in
      determining dyadic responding.

PMID- 23548575
TI  - Toll-like receptor 3 expression in glia and neurons alters in response to white
      matter injury in preterm infants.
AB  - Toll-like receptors (TLRs) are members of the pattern recognition receptor family
      that detect components of foreign pathogens or endogenous molecules released in
      response to injury. Recent studies demonstrate that TLRs also have a functional
      role in regulating neuronal proliferation in the developing brain. This study
      investigated cellular expression of TLR3 using immunohistochemistry on human
      brain tissue. The tissue sections analysed contained anterior and lateral
      periventricular white matter from the frontal and parietal lobes in post-mortem
      neonatal cases with a postmenstrual age range of 23.6-31.4 weeks. In addition to
      preterm brains without overt pathology (control), preterm pathology cases with
      evidence of white matter injuries (WMI) were also examined. In order to identify
      TLR-positive cells, we utilized standard double-labelling immunofluorescence co
      labelling techniques and confocal microscopy to compare co-expression of TLR3
      with a neuronal marker (NeuN) or with glial markers (GFAP for astrocytes, Iba-1
      for microglia and Olig2 for oligodendrocytes). We observed an increase in the
      neuronal (28 vs. 17%) and astroglial (38 vs. 21%) populations in the WMI group
      compared to controls in the anterior regions of the periventricular white matter
      in the frontal lobe. The increase in neurons and astrocytes in the WMI cases was
      associated with an increase in TLR3 immunoreactivity. This expression was
      significantly increased in the astroglia. The morphology of the TLR3 signal in
      the control cases was globular and restricted to the perinuclear region of the
      neurons and astrocytes, whilst in the cases of WMI, both neuronal, axonal and
      astroglial TLR3 expression was more diffuse (i.e., a different intracellular
      distribution) and could be detected along the extensions of the processes. This
      study demonstrates for the first time that neurons and glial cells in human
      neonatal periventricular white matter express TLR3 during development. The
      patterns of TLR3 expression were altered in the presence of WMI, which might
      influence normal developmental processes within the immature brain. Identifying
      changes in TLR3 expression during fetal development may be key to understanding
      the reduced volumes of grey matter and impaired cortical development seen in
      preterm infants. 

PMID- 23548576
TI  - Should the negativity for islet cell autoantibodies be used in a prescreening for
      genetic testing in maturity-onset diabetes of the young? The case of autoimmunity
      associated destruction of pancreatic beta-cells in a family of HNF1A-MODY
      subjects.
AB  - It was recently suggested that routine islet cell autoantibody testing should be
      performed to discriminate maturity-onset diabetes of the young (MODY) from type 1
      diabetes mellitus (T1DM). This is the first report ever to describe the familial
      manifestation of T1DM autoimmunity in nonobese HNF1A-MODY subjects and the
      presence of islet antigen-2 (IA-2) antibodies in MODY subjects. Three nonobese
      subjects in an age range of 14-35 years were diagnosed with HNF1A-MODY (p.
      Arg159Gln mutation). All the tested subjects had detectable (but varying) levels
      of islet cell autoantibodies (i.e., antibodies against glutamate decarboxylase or
      IA-2) in the absence of other T1DM characteristics. They displayed long-term
      expression of intermediate fasting C-peptide levels, ketoacidosis was absent even
      in periods of spontaneous insulin withdrawal, and full dependence on externally
      administered insulin was not detected in any of them although better glycemic
      control was achieved when insulin was supplemented. The course of the disease was
      similar to that of the autoantibody-negative HNF1A-MODY subjects. The case
      questions the selectivity of autoantibodies as a marker of T1DM or late-onset
      autoimmune diabetes of adulthood (LADA) over MODY and challenges the use of
      autoantibodies as a universal negative marker of MODY in an effort to decrease
      the cost of health care, as it may eventually lead to the wrong diagnosis and
      thus to the incorrect treatment. Further research should involve examination of
      the autoantibody titers and prevalence in large and geographically diverse
      cohorts of MODY subjects selected for genetic testing (regardless of their
      autoantibody titers) as well as determination of the islet cell autoantibody
      kinetics in the course of MODY onset and progression.

PMID- 23548577
TI  - Simulation for ward processes of surgical care.
AB  - The role of simulation in surgical education, initially confined to technical
      skills and procedural tasks, increasingly includes training nontechnical skills
      including communication, crisis management, and teamwork. Research suggests that
      many preventable adverse events can be attributed to nontechnical error occurring
      within a ward context. Ward rounds represent the primary point of interaction
      between patient and physician but take place without formalized training or
      assessment. The simulated ward should provide an environment in which processes
      of perioperative care can be performed safely and realistically, allowing
      multidisciplinary assessment and training of full ward rounds. We review existing
      literature and describe our experience in setting up our ward simulator. We
      examine the facilities, equipment, cost, and personnel required for establishing
      a surgical ward simulator and consider the scenario development, assessment, and
      feedback tools necessary to integrate it into a surgical curriculum. 

PMID- 23548578
TI  - Survival after surgery for hepatocellular carcinoma in relation to presence or
      absence of viral infection.
AB  - BACKGROUND: The aim of this study was to compare postoperative survival between
      hepatocellular carcinoma (HCC) patients with and without viral infection.
      METHODS: From among 398 HCC patients in our collected database, 377 who underwent
      surgery were enrolled. The patients were divided into 2 groups: group 1, those
      who had no hepatitis B virus or hepatitis C virus infection, and group 2, those
      who had hepatitis B virus or hepatitis C virus infection. Univariate analysis was
      performed to compare clinical factors, including viral infection, with overall
      survival. Kaplan-Meier analysis and the log-rank test were used to evaluate the
      overall and disease-free survival curves for the 2 groups. RESULTS: Univariate
      analysis showed that viral infection showed no such association. Moreover, Kaplan
      Meier analysis and the log-rank test revealed no significant intergroup
      differences in either overall or disease-free survival. CONCLUSIONS: The presence
      or absence of viral infection shows no significant association with the
      postoperative survival of patients undergoing surgery for HCC.

PMID- 23548579
TI  - Genetic mutations in patients with acute myeloid leukemia and leukostasis.

PMID- 23548580
TI  - Relating centromeric topography in fixed human chromosomes to alpha-satellite DNA
      and CENP-B distribution.
AB  - Despite extensive analyses on the centromere and its associated proteins,
      detailed studies of centromeric DNA structure have provided limited information
      about its topography in condensed chromatin. We have developed a method with
      correlative fluorescence light microscopy and atomic force microscopy that
      investigates the physical and structural organization of alpha-satellite DNA
      sequences in the context of its associated protein, CENP-B, on human metaphase
      chromosome topography. Comparison of centromeric DNA and protein distribution
      patterns in fixed homologous chromosomes indicates that CENP-B and alpha
      satellite DNA are distributed distinctly from one another and relative to
      observed centromeric ridge topography. Our approach facilitates correlated
      studies of multiple chromatin components comprising higher-order structures of
      human metaphase chromosomes.

PMID- 23548581
TI  - Week-to-week differences of children's habitual activity and postural allocation
      as measured by the ActivPAL monitor.
AB  - BACKGROUND: Quantification of sitting and standing is possible with the ActivPAL
      accelerometer, using algorithms to classify activity into time spent sitting,
      standing and stepping. The purpose of this study was to determine children's week
      to-week differences in time spent sitting/lying and standing along with other
      measures as provided by the ActivPAL accelerometer during continuous wearing of
      the ActivPAL monitor. METHODS: Fifty-six children (age 10.2+/-0.9 years, mean+/
      SD) were recruited from 30 urban schools in Auckland, New Zealand. Children wore
      the monitor for 24h per day up to 14 days. Analyses were performed with mixed
      modeling. Reliability was expressed as change in the mean from week to week,
      intraclass correlation coefficient (ICC) and standard error of measurement (SEM).
      RESULTS: Mean week-to-week differences in percent time spent sitting/lying,
      standing and stepping on week days and weekend days for girls and boys were
      typically small. Step and sit-to-stand counts differences were small and unclear
      respectively. ICC values ranged from 0.40 to 0.79 during week days and 0.25-0.60
      during weekends. SEM for time spent sitting/lying, standing and stepping were
      ~3.5%, ~2.5% and ~1.5% respectively. CONCLUSION: The ActivPAL showed moderate to
      low week-to-week reliability for habitual activity and postural allocation under
      free living conditions in boys and girls. Interventions aimed at a moderate
      reduction in sitting time (~5% of the day) will require modest sample sizes for
      adequate precision.

PMID- 23548583
TI  - Nrf2-dependent neuroprotective activity of diterpenoids isolated from Sideritis
      spp.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The species of the genus Sideritis are
      extensively used in the Mediterranean area in folk medicine for their digestive,
      antimicrobial, anti-inflammatory and antioxidant properties, among others.
      Moreover, Sideritis species as tea infusions are popularly known for improving
      memory function and cognitive ability. Diterpenoids are one of the most abundant
      and important pharmacological interest of the classes of natural products
      presented in these medicinal plants. AIM OF THE STUDY: To determine for the first
      time the neuroprotective effects, based on their antioxidant properties, of the
      three isolated major diterpenoids andalusol, conchitriol and lagascatriol in an
      oxidative stress model. MATERIALS AND METHODS: H2O2 was used as oxidant inductor
      and rat adrenal pheochromocytoma PC12 cells as cellular model. Cell viability was
      measured using MTT and LDH assays, lipid peroxidation was determined by HPLC, GSH
      and GSSG levels assessed by fluorometric techniques, enzymatic activity and
      protein expression were determined by spectrofometric techniques and Western
      blot, respectively. RESULTS: Pretreatments with the three diterpenoids
      significantly attenuated H2O2-induced changes in mitochondrial integrity and
      activity (MTT assay), in cell membrane integrity (LDH assay) and in cell
      morphology. Moreover, these diterpenoids inhibited intracellular ROS production
      H2O2-induced, reduced lipid peroxidation and counteracted GSH/GSSG changes.
      Furthermore, both activities and protein expression of the endogenous antioxidant
      enzymes (CAT, SOD, GR, GPx and HO-1) were increased. The Nrf2 pathway was
      involved, at least in part, in the protective effects of these diterpenoids.
      CONCLUSION: These findings suggest that these natural compounds provide
      significant antioxidant effects in PC12 under for counteracting the oxidative
      damage H2O2-induced and their potential role as useful agents for the prevention
      of those oxidative stress-mediated dementia disorders. Andalusol was the most
      active compound among the studied diterpenoids.

PMID- 23548582
TI  - Blockage of peripheral NPY Y1 and Y2 receptors modulates barorefex sensitivity of
      diabetic rats.
AB  - BACKGROUND/AIMS: Abnormal baroreceptor reflex sensitivity (BRS) and elevated
      plasma neuropeptide Y (NPY) are prevalent in diabetic patients. The present study
      was conducted to determine whether NPY Y1 receptor (Y1R) and NPY Y2 receptor
      (Y2R) contribute to the regulatin of BRS in diabetic rats. METHODS: Diabetes
      mellitus (DM) rats with hyperlipidemia were developed by an emulsion diet
      enriched with fat, sucrose and fructose followed by streptozocin (STZ). Y1R and
      Y2R specific antagonists (BIBP 3226 and BIIE 0246) were administered by a mini
      osmotic pump. Systolic blood pressure (SBP), heart rate (HR), BRS and heart
      functions, as well as the plasma NPY and lipid level were measured after
      treatment for 4 weeks. RESULTS: Both BIBP 3226 and BIIE 0246 treatment reversed
      the elevated total cholesterol (TC) and low density lipoprotein (LDL-C) level,
      and reduced high density lipoprotein (HDL-C) level in DM rats. BIIE 0246 may
      attenuate the increased triglyceride (TG) level in DM rats. In addition, neither
      BIBP 3226 nor BIIE 0246 treatment produced significant effects on BRS, SBP or HR
      (P>0.05) in DM rats, even after PE and SNP challenge. However, BIBP 3226 and BIIE
      0246 further impaired LVSP, LVEDP, +dp/dtmax and -dp/dtmax. CONCLUSION: This
      study provided us with the evidence that the inhibition of peripheral Y1R and Y2R
      did not affect impaired BRS but amplified the deterioration of the compromised
      cardiac function in STZ-induced DM rats with hyperlipidemia.

PMID- 23548584
TI  - Aqueous extract of Artemisia capillaris exerts hepatoprotective action in alcohol
      pyrazole-fed rat model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia capillaris, also called "InJin" in
      Korean, has been widely used to treat various hepatic disorders in traditional
      Oriental medicine. AIMS: The purpose of this study is to evaluate the
      hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on
      alcoholic liver injury. MATERIALS AND METHODS: Liver injury was induced by oral
      administration of 30% alcohol (10 mL/kg, twice per day) plus pyrazole (PRZ, 30
      mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin
      (50mg/kg) for 10 days. The hepatoprotective effects were assessed by observing
      histopathological changes, hepatic transaminase enzymes, hepatic oxidation and
      antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in
      serum and hepatic gene expression level, respectively. RESULTS: Alcohol-PRZ
      treatment drastically increased the serum levels of aspartate transaminase (AST),
      alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver
      tissues while these changes were significantly ameliorated by WAC administration
      (p<0.05 or 0.01). The prominent microvesicular steatosis and mild necrosis in
      hepatic histopathology were induced by alcohol-PRZ treatment, but notably
      attenuated by WAC administration. Moreover, the alcohol-PRZ treatment-induced
      depletions of the antioxidant components including glutathione content, total
      antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px),
      reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly
      ameliorated by WAC administration (p<0.05, except GSH-Rd). These results were in
      accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase
      1 (HO-1) gene expression. Alcohol-PRZ treatment increased the levels of tumor
      necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta)
      in hepatic tissues. However they were significantly normalized by WAC
      administration (p<0.05 or 0.01). In addition, WAC administration significantly
      attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and
      hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH). CONCLUSIONS:
      These results support the relevance in clinical use of Artemisia capillaris for
      alcohol-associated hepatic disorders. The underlying mechanisms may involve both
      enhancement of antioxidant activities and modulation of proinflammatory
      cytokines.

PMID- 23548585
TI  - Extended solvent-contact model for protein solvation: test cases for dipeptides.
AB  - Solvation effects are critically important in the structural stabilization and
      functional optimization of proteins. Here, we propose a new solvation free energy
      function for proteins, and test its applicability in predicting the solvation
      free energies of dipeptides. The present solvation model involves the improvement
      of the previous solvent-contact model assuming that the molecular solvation free
      energy could be given by the sum over the individual atomic contributions. In
      addition to the existing solvent-contact term, the modified solvation free energy
      function includes the self-solvation term that reflects the effects of
      intramolecular interactions in the solute molecule on solute-solvent
      interactions. Four kinds of atomic parameters should be determined in this
      solvation model: atomic fragmental volume, maximum atomic occupancy, atomic
      solvation, and atomic self-solvation parameters. All of these parameters for 16
      atom types are optimized with a standard genetic algorithm in such a way to
      minimize the difference between the solvation free energies of dipeptides
      obtained from high-level quantum chemical calculations and those predicted by the
      solvation free energy function. The solvation free energies of dipeptides
      estimated from the new solvation model are in good agreement with the quantum
      chemical results. Therefore, the optimized solvation free energy function is
      expected to be useful for examining the structural and energetic features of
      proteins in aqueous solution.

PMID- 23548586
TI  - Benchtop comparison of a novel dynamic compression screw to a standard cortical
      screw: compression integrity and gap size over time during simulated resorption.
AB  - Literature reports the incidence of failed isolated foot and ankle fusions as up
      to 23%. A contributing factor is the natural bone resorption, which occurs
      resulting in loss of compression and gapping at the fusion site when standard
      static compression plates and screws are used. However, an innovative dynamic
      compression screw may provide lasting compression despite resorption. This
      benchtop study shows that the FxDEVICES spring-loaded dynamic POGO screw
      maintains more compression and more consistent compression rate during simulated
      resorption, as compared with a standard compression screw. The novel screw
      maintained much greater compression strength within the first millimeter of
      simulated resorption (13.57 vs 4.38 lb) and maintained greater compression
      strength at the test completion (1.14 vs 0 lb). The novel screw revealed a more
      consistent resorption rate over the duration of the simulation. Clinically, this
      may result in more stability and improved fusion rates.

PMID- 23548587
TI  - Bone wax: a foreign body/giant cell reaction in the foot.
AB  - Bone wax has been used for years by surgeons as a hemostatic agent to prevent
      bleeding from bone surfaces. Though the effectiveness of bone wax as a hemostatic
      agent while acting as a tamponade is well known, it is not without its
      complications. It has been documented in the medical literature that bone wax may
      remain in the body for many years as a foreign body and in some cases cause a
      giant cell reaction at various surgical sites. However, to the authors'
      knowledge, there has not been a reported case of a foreign body giant cell
      reaction secondary to the use of bone wax in the current podiatric literature.
      Two case studies are described to bring attention to the fact that bone wax can
      interfere with bone healing while remaining attached to bone as a foreign body
      and induce a giant cell reaction and local inflammatory effects in the human
      foot.

PMID- 23548588
TI  - Prenatal hypoxia downregulates the expression of pulmonary vascular endothelial
      growth factor and its receptors in fetal mice.
AB  - BACKGROUND: Previous reports showed that prenatal hypoxia delays the process of
      lung maturation. Vascular endothelial growth factor (VEGF) and its receptors were
      important for lung development. However, the role of VEGF and VEGF receptors in
      altered fetal lung development and maturation induced by prenatal hypoxia remains
      unknown. OBJECTIVES: To elucidate the role of VEGF and VEGF receptors in altered
      fetal lung development and maturation induced by prenatal hypoxia. METHODS: Lung
      sections of control and maternal hypoxic fetal mice were used for the
      determination of lung development and total RNA isolated from lung homogenates
      were used for determination of the expression patterns of VEGF, Flt-1, Flk-1,
      hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, surfactant protein (SP)-A, SP
      B, SP-C, and SP-D by quantitative real-time RT-PCR. RESULTS: Prenatal hypoxia
      resulted in fetal mice body weight gain impairment, delayed fetal pulmonary
      aeration and maturation. Pulmonary SP-A, SP-B, SP-C, and SP-D mRNA were all
      decreased in the prenatal hypoxia group. In addition, we demonstrated that
      prenatal hypoxia inhibited the developmental increase of pulmonary HIF-1alpha and
      HIF-2alpha expression and resulted in decreasing VEGF and its receptors (Flt-1
      and Flk-1) at the mRNA expression level and VEGF protein level in fetal lungs.
      These inhibitory effects persisted and progressed even when the dams were
      returned to air. CONCLUSIONS: We suggest that prenatal hypoxia insults, at least
      in late gestation, influence pulmonary VEGF and VEGF receptor expression through
      the down-regulation of HIF pathways and impair fetal lung growth and maturation.

PMID- 23548589
TI  - Assessing community pharmacist engagement in a policing partnership strategy to
      reduce the illicit diversion of pseudoephedrine products.
AB  - BACKGROUND: The incidence of illicit diversion of pharmaceutical products is a
      worldwide problem associated with negative health consequences and with other
      crimes. The illicit diversion of pharmaceuticals containing the active ingredient
      pseudoephedrine is of concern, primarily due to the role this substance plays in
      the manufacture of synthetic illicit drugs such as methylamphetamine. There are a
      range of strategies employed to curb the problem of precursor diversion. Not
      least is the development of strategies involving front-line health professionals
      such as community pharmacists to play an important role in reducing the incidence
      of diversion. OBJECTIVES: This study aimed to examine levels of pharmacist
      engagement in an intervention expected to decrease diversion of pseudoephedrine
      products from community pharmacies. The primary objective was to explore levels
      of community pharmacist engagement with the intervention and to explore their
      perceptions of intervention effectiveness. METHODS: A survey instrument was
      developed to examine six main areas relating to the implementation, operation and
      outcomes of the intervention, in addition to the roles performed by community
      pharmacists in two Australian State jurisdictions. The respondent pharmacists
      were recruited through a combination of email and facsimile communications from
      the Pharmacy Guild of Australia and through an electronic pharmacy newsletter.
      RESULTS: Thirty percent of eligible community pharmacies in the study
      jurisdictions responded to the survey. The results of the survey highlight that
      in the absence of an alternative strategy to assist community pharmacists to
      reduce pseudoephedrine diversion, the majority of respondents were satisfied with
      the effectiveness of the police-pharmacy intervention. It was found that a
      pharmacist's positive perception of the role police played in the intervention
      strongly influenced their engagement in the strategy. CONCLUSION: Identifying the
      factors that significantly influence pharmacist engagement in this strategy has
      broader implications for other law enforcement-public health strategies. It is
      important for policy models to incorporate these significant elements in their
      design to enhance the implementation, operation and outcomes of prevention-type
      interventions.

PMID- 23548590
TI  - Prenatal diagnosis of congenital epulis by 2D/3D ultrasound and magnetic
      resonance.
AB  - Congenital epulis is a rare benign oral cavity tumor that usually arises from the
      maxillary alveolar mucosa. It is also known as congenital gingival granular cell
      tumor. Prenatal diagnosis is uncommon and mostly confined to the third trimester.
      We report a case of congenital epulis, which was referred to our department at 35
      weeks of gestation. Both images from our prenatal 2D/3D ultrasound (including
      Doppler technique) and magnetic resonance examination are presented. A baby girl
      weighing 2,800 g was delivered spontaneously at 36 weeks and 1 day. The newborn
      had to be intubated immediately after delivery. A simple excision of the mass was
      performed on the first day of neonatal life after clinical examination by our
      pediatric stomatologists confirmed the presence of a tumor resembling epulis. The
      correctness of this diagnosis was subsequently confirmed by histogenesis.
      Photographs from the operating room show the postnatal appearance of the tumor.
      The baby was discharged at the age of 19 days and has remained well at follow-up
      controls.

PMID- 23548591
TI  - Assessment of nanosilver toxicity during zebrafish (Danio rerio) development.
AB  - Nanomaterials (NMs) including silver nanoparticles (AgNPs) are incorporated into
      an increasing number of consumer and medical products. However, the potential
      toxicity of AgNPs to aquatic organisms is largely unknown. This study
      characterizes the effects of AgNPs on zebrafish (Danio rerio) development. The
      effects of silver ions (Ag(+)) and AgNPs were examined at equivalent Ag
      concentrations, which ranged from 0.03 to 1.55 MUg mL(-1) total Ag. The Ag(+) was
      more toxic than AgNPs but both lead to death and delayed hatching in surviving
      embryos. Both silver types depleted glutathione levels but generally did not
      affect antioxidant enzymes activities. In addition to silver some of the embryos
      were also exposed to cysteine, which generally reduced the toxicity of both
      silver types. This study demonstrates that AgNPs and Ag(+) are capable of
      inducing toxicity in zebrafish embryos including the induction of oxidative
      stress.

PMID- 23548592
TI  - A memory already like an elephant's? The advanced brain morphology of the last
      common ancestor of Afrotheria (Mammalia).
AB  - Virtually reconstructed and natural endocranial casts are used in the study of
      brain evolution through geological time. We here present work investigating the
      paleoneurological evolution of afrotherian mammals. Using microCT-generated
      endocasts we show that, with the exception of the subfamilies Macroscelidinae and
      Tenrecoidea, most Afroinsectiphilia display a more or less gyrencephalic and
      ventrally expanded neopallium, two derived features that are unexpected for these
      insectivore-grade afrotherians. This implies that the endocranial cast morphology
      at the root of the afrotherian clade may have been more advanced than previously
      thought. The reconstructed endocranial morphology of the Afrotheria's last common
      ancestor reaches the level of complexity of some early Cenozoic archaic
      ungulates. Our result gives support to the hypothesis of an ungulate-like
      ancestral body plan for Afrotheria. It also implies that the a priori 'primitive'
      suite of traits evident in the brain of Afroinsectivora, especially in the
      tenrecs, may have been secondarily acquired. Implications on the overestimation
      of the divergence age of Afrotheria are discussed.

PMID- 23548594
TI  - Maternal separation alters serotonergic and HPA axis gene expression independent
      of separation duration in mice.
AB  - Adverse early life experiences (aELEs), such as child abuse, neglect, or trauma,
      increase lifetime vulnerability for mental illness. In this study, aELEs were
      modeled in c57bl/6 mice using the maternal separation (MS) paradigm, in which
      pups were separated for 180 min/day (MS180), 15 min/day (MS15), or left
      undisturbed (AFR) from postnatal day 2-14. As adults, pups that experienced MS15
      or MS180 demonstrated decreases in tryptophan hydroxylase 2 and serotonin
      transporter mRNA in the dorsal raphe dorsalis and ventralis, and increases in
      glucocorticoid receptor mRNA in the dentate gyrus of the hippocampus. To
      investigate factors underlying shared expression between MS conditions, dam on
      nest time and DNA methylation at the TPH2 promoter and 5' UTR were assessed. Post
      reunion on-nest time increased as a function of separation duration, potentially
      serving as a mitigating factor underlying similar expression between MS
      conditions. TPH2 DNA methylation remained unchanged, suggesting changes in TPH2
      mRNA are not mediated by changes in DNA methylation of this region. The shared
      pattern of expression between MS15 and MS180 conditions suggests a species- or
      strain- specific response to MS unique to c57bl/6 mice.

PMID- 23548595
TI  - Disrupted connectivity of motor loops in Parkinson's disease during self
      initiated but not externally-triggered movements.
AB  - Parkinson's disease (PD) reportedly includes altered connectivity of neural loops
      involving the basal ganglia and cerebellum, although little is known regarding
      any changes in the connectivity of motor loops. The goal of this study was to
      further understand the connectivity within the basal ganglia-thalamo-motor (BGTM)
      and cerebro-cerebellar (CC) loops in PD. Twelve PD patients and 12 age-matched
      control subjects performed a protocol involving self-initiated (SI) and
      externally-triggered (ET) finger movements, while being scanned with functional
      magnetic resonance imaging. Compared with the control subjects, the PD subjects
      showed hypo-activation in the bilateral putamen, right supplementary motor area
      and hyper-activation in the right premotor cortex. In the sensorimotor cortex and
      cerebellar hemisphere, PD subjects tended to show hyper-activation in a main
      effects analysis, but hypo-activation in a linear effects analysis. Analysis
      using structural equation modeling (SEM) revealed significant positive
      interactions within the right BGTM loop during the SI task and within the right
      (right cerebral hemisphere-left cerebellum) CC loop during the ET task. SEM also
      revealed task-related quantitative changes between the thalamus and the motor
      cortices in the control subjects. We found that the PD patients showed reduced
      connectivity in the right BGTM loop and inter-hemispheric connections in SEM,
      which is the first demonstration of this phenomenon. Interestingly, PD patients
      exhibited preserved connectivity within the right CC loop during the ET task.
      These results suggest disruption of cortico-striatal processing and preservation
      of relatively intact neural circuits that do not involve the basal ganglia in PD.

PMID- 23548596
TI  - Brain axial and radial diffusivity changes with age and gender in healthy adults.
AB  - White matter integrity changes with age, with the extent of variation dependent
      on attributes such as sex and oligodendrocyte health. Quantification of myelin
      and axonal integrity in healthy people would provide normative values necessary
      to determine pathology-related tissue characteristics with normal-aging and
      gender. We assessed white matter integrity with diffusion tensor imaging-based
      axial and radial diffusivity procedures (3.0-Tesla magnetic resonance imaging),
      which measure water diffusion parallel and perpendicular to axonal bundles,
      indicating axonal and myelin status, respectively, using region-of-interest (ROI)
      analyses, in 34 healthy adults (age, 46.5 +/- 6.0 years, 19 male). Sex
      differences in diffusion values were assessed with two-sample t-tests, and
      diffusion changes with age using Pearson's correlations; whole-brain effect sizes
      were examined with voxel-based procedures. Multiple brain areas showed increased
      axial and radial diffusivity values reflecting declines in axonal and myelin
      integrity with age, especially in mid-hippocampal and posterior thalamic areas.
      However, axonal and myelin integrity increased in insular and occipital cortex
      projections with maturity. Females showed reduced fiber and myelin integrity in
      substantially more structures than males, and those areas included limbic, basal
      ganglia, pontine, and cerebellar sites. A minority of structures, confined to
      cerebellar, temporal, and frontal cortices, showed reduced fiber and myelin
      integrity with age in males over females. Whole-brain effect sizes in diffusion
      values between sexes and age-related changes showed findings parallel to ROI
      analyses. The structural differences mandate partitioning of sex and age in adult
      white matter pathology assessment, and likely contribute to sex-based
      physiological and behavioral dysfunction in aging and in multiple pathologies.

PMID- 23548597
TI  - Orexin in the chicken hypothalamus: immunocytochemical localisation and
      comparison of mRNA concentrations during the day and night, and after chronic
      food restriction.
AB  - In mammals Orexin-A and -B are neuropeptides involved in the hypothalamic
      regulation of diverse physiological functions including food intake and the sleep
      wake cycle. This generalisation was investigated in meat-(broiler) and layer-type
      juvenile domestic chickens by immunocytochemical localisation of orexin A/B in
      the hypothalamus, and by measurements of hypothalamic hypocretin mRNA which
      encodes for orexin A/B after chronic food restriction, and during the sleep-wake
      cycle. Orexin immunoreactive fibres were observed throughout the hypothalamus
      with cell bodies in and around the paraventricular nucleus. No differences were
      observed in the pattern of immunoreactivity using anti- human orexin-A, or -B
      antisera. The amount of hypothalamic hypocretin mRNA in food -restricted broilers
      was higher than in broilers fed ad libitum, but the same as in layer- type hens
      fed ad libitum. Hypothalamic hypocretin mRNA was increased (P<0.01) in 12-week
      old broilers fed 25% of their ad libitum intake between 6-12 weeks of age. No
      difference in hypothalamic hypocretin mRNA was seen in 12-week-old layer- type
      hens when they were awake (1-2h after lights on) or sleeping (1-2h after lights
      off). It is concluded that in the chicken, we could not find evidence that
      hypothalamic orexin plays a role in the sleep-wake cycle and it may be involved
      in aspects of energy balance.

PMID- 23548598
TI  - Involvement of PI3K and ROCK signaling pathways in migration of bone marrow
      derived mesenchymal stem cells through human brain microvascular endothelial cell
      monolayers.
AB  - Bone marrow-derived mesenchymal stem cells (MSC) represent an important and
      easily available source of stem cells for potential therapeutic use in
      neurological diseases. The entry of circulating cells into the central nervous
      system by intravenous administration requires, firstly, the passage of the cells
      across the blood-brain barrier (BBB). However, little is known of the details of
      MSC transmigration across the BBB. In the present study, we employed an in vitro
      BBB model constructed using a human brain microvascular endothelial cell
      monolayer to study the mechanism underlying MSC transendothelial migration.
      Transmigration assays, transendothelial electrical resistance (TEER) and
      horseradish peroxidase (HRP) flux assays showed that MSC could transmigrate
      through human brain microvascular endothelial cell monolayers by a paracellular
      pathway. Cell fractionation and immunofluorescence assays confirmed the
      disruption of tight junctions. Inhibition assays showed that a Rho-kinase (ROCK)
      inhibitor (Y27632) effectively promoted MSC transendothelial migration;
      conversely, a PI3K inhibitor (LY294002) blocked MSC transendothelial migration.
      Interestingly, adenovirus-mediated interference with ROCK in MSC significantly
      increased MSC transendothelial migration, and overexpression of a PI3K dominant
      negative mutant in MSC cells could block transendothelial migration. Our findings
      provide clear evidence that the PI3K and ROCK pathways are involved in MSC
      migration through human brain microvascular endothelial cell monolayers. The
      information yielded by this study may be helpful in constructing gene-modified
      mesenchymal stem cells that are able to penetrate the BBB effectively for cell
      therapy.

PMID- 23548600
TI  - Atorvastatin improves cognitive, emotional and motor impairments induced by
      intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in
      rats, an experimental model of Parkinson's disease.
AB  - Affective disorders and memory impairments precede the classical motor symptoms
      seen in Parkinson's disease (PD) and the currently approved antiparkinsonian
      agents do not alleviate the non-motor symptoms as well as the underlying
      dopaminergic neuron degeneration. On the other hand, there is increasing evidence
      that inflammation plays a key role in the pathophysiology of PD and that the anti
      inflammatory actions of statins are related to their neuroprotective properties
      against different insults in the CNS. The present data indicates that the oral
      treatment with atorvastatin (10mg/kg/day), once a day during 7 consecutive days,
      was able to prevent short-term memory impairments and depressive-like behavior of
      rats assessed in the social recognition and forced swimming tests at 7 and 14
      days, respectively, after a single intranasal (i.n.) administration of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1mg/nostril). Importantly, at this time
      no significant alterations on the locomotor activity of the animals were observed
      in the open field test. Moreover, atorvastatin was found to protect against the
      long-lasting motor deficits evaluated in activity chambers and the loss of
      dopaminergic neurons in the substantia nigra pars compacta observed at 21 days
      after i.n. MPTP administration. At this time, despite the absence of spatial
      memory deficits in the water maze and in concentrations of the cytokines TNF
      alpha, IL-1beta and IL-10 in striatum and hippocampus following i.n. MPTP
      administration, atorvastatin treatment resulted in a significant increase in the
      striatal and hippocampal levels of nerve growth factor (NGF). These findings
      reinforce and extend the notion of the neuroprotective potential of atorvastatin
      and suggest that it may represent a new therapeutic tool for the management of
      motor and non-motor symptoms of PD.

PMID- 23548599
TI  - High-fat diet feeding causes rapid, non-apoptotic cleavage of caspase-3 in
      astrocytes.
AB  - Astrocytes respond to multiple forms of central nervous system (CNS) injury by
      entering a reactive state characterized by morphological changes and a specific
      pattern of altered protein expression. Termed astrogliosis, this response has
      been shown to strongly influence the injury response and functional recovery of
      CNS tissues. This pattern of CNS inflammation and injury associated with
      astrogliosis has recently been found to occur in the energy homeostasis centers
      of the hypothalamus during diet-induced obesity (DIO) in rodent models, but the
      characterization of the astrocyte response remains incomplete. Here, we report
      that astrocytes in the mediobasal hypothalamus respond robustly and rapidly to
      purified high-fat diet (HFD) feeding by cleaving caspase-3, a protease whose
      cleavage is often associated with apoptosis. Although obesity develops in HFD-fed
      rats by day 14, caspase-3 cleavage occurs by day 3, prior to the development of
      obesity, suggesting the possibility that it could play a causal role in the
      hypothalamic neuropathology and fat gain observed in DIO. Caspase-3 cleavage is
      not associated with an increase in the rate of apoptosis, as determined by TUNEL
      staining, suggesting it plays a non-apoptotic role analogous to the response to
      excitotoxic neuron injury. Our results indicate that astrocytes in the mediobasal
      hypothalamus respond rapidly and robustly to HFD feeding, activating caspase-3 in
      the absence of apoptosis, a process that has the potential to influence the
      course of DIO.

PMID- 23548601
TI  - Intracellular calcium level is an important factor influencing ion channel
      modulations by PLC-coupled metabotropic receptors in hippocampal neurons.
AB  - Signaling pathways involving phospholipase C (PLC) are involved in various neural
      functions. Understanding how these pathways are regulated will lead to a better
      understanding of their roles in neural functions. Previous studies demonstrated
      that receptor-driven PLCbeta activation depends on intracellular Ca(2+)
      concentration ([Ca(2+)]i), suggesting the possibility that PLCbeta-dependent
      cellular responses are basically Ca(2+) dependent. To test this possibility, we
      examined whether modulations of ion channels driven by PLC-coupled metabotropic
      receptors are sensitive to [Ca(2+)]i using cultured hippocampal neurons.
      Muscarinic activation triggered an inward current at -100 mV (the equilibrium
      potential for K(+)) in a subpopulation of neurons. This current response was
      suppressed by pirenzepine (an M1-preferring antagonist), PLC inhibitor, non
      selective cation channel blocker, and lowering [Ca(2+)]i. Using the neurons
      showing no response at -100 mV, effects of muscarinic activation on K(+) channels
      were examined at -40 mV. Muscarinic activation induced a transient decrease of
      the holding outward current. This current response was mimicked and occluded by
      XE991, an M-current K(+) channel blocker, suppressed by pirenzepine, PLC
      inhibitor and lowering [Ca(2+)]i, and enhanced by elevating [Ca(2+)]i. Similar
      results were obtained when group I metabotropic glutamate receptors were
      activated instead of muscarinic receptors. These results clearly show that ion
      channel modulations driven by PLC-coupled metabotropic receptors are dependent on
      [Ca(2+)]i, supporting the hypothesis that cellular responses induced by receptor
      driven PLCbeta activation are basically Ca(2+) dependent.

PMID- 23548602
TI  - Oxytocin action in the ventral tegmental area affects sucrose intake.
AB  - Brain oxytocin is known to play a role in the control of food intake, and recent
      studies suggest that stimulation of central oxytocin receptors selectively
      suppresses carbohydrate intake. The specific oxytocin projection sites and
      receptor populations involved in this response are as yet unidentified. We
      hypothesized that oxytocin receptors in the ventral tegmental area (VTA) may play
      a role in limiting sucrose intake, because the VTA is known to influence
      palatable food intake. We first performed a dose response study in which we
      observed that intra-VTA oxytocin injection significantly suppressed intake of a
      10% sucrose solution during a 30-min test session by 13.35-20.5% relative to
      vehicle treatment. Doses of intra-VTA oxytocin that suppressed sucrose intake had
      no effect on water intake. Next we examined the effects of two oxytocin receptor
      antagonists, (d(CH2)5(1),Tyr(Me)(2),Orn(8))-Oxytocin (OVT) and L-368,899. Each of
      these antagonists significantly increased 10% sucrose intake by 17-20.5% relative
      to vehicle when delivered directly into the VTA, at doses subthreshold for effect
      if injected into the cerebral ventricles. Finally, we observed that the effect of
      intra-VTA oxytocin to suppress 10% sucrose intake was significantly attenuated by
      pretreatment with L-368,899, supporting the suggestion that the VTA oxytocin
      treatment suppresses intake through action at oxytocin receptors. These findings
      support the suggestion that endogenous oxytocin action within the VTA suppresses
      sucrose intake. We conclude that oxytocin receptors in the VTA play a physiologic
      role in the control of sucrose ingestion.

PMID- 23548603
TI  - Effect of tipepidine with novel antidepressant-like action on c-fos-like protein
      expression in rat brain.
AB  - We previously reported that tipepidine, a centrally acting non-narcotic
      antitussive, has an antidepressant-like effect in normal and imipramine treatment
      resistant depression model rats. Recently, mapping the induction of c-fos-like
      immunoreactivity (FLI) in the rat brain showed FLI-positive neurons in several
      brain areas after acute administration of different classes of antidepressants.
      Here, the effect of a single injection of an antidepressive dose of tipepidine on
      FLI was studied in seven areas of the rat brain including the central nucleus of
      the amygdala (CeA) and the nucleus accumbens (NAc). Desipramine was also used for
      comparison. Rats were anesthetized and perfused 2h after injection with
      tipepidine (20 and 40mg/kg, i.p.), desipramine (10mg/kg, i.p.), or saline. Then,
      immunostaining of FLI-positive neurons in brain slices was performed with
      conventional methods. A single injection of tipepidine increased FLI-positive
      neurons in the CeA, similar to preexisting antidepressants, and induced the
      characteristic pattern of an increase in FLI-positive neurons in six other brain
      areas including the NAc, an effect that was different from other antidepressants.
      In addition, a single injection of desipramine (10mg/kg) or tipepidine (20mg/kg)
      decreased the immobility time in the forced swimming test to a similar extent.
      The results obtained from the previous behavioral study and the current
      immunohistochemical study suggest that tipepidine may be a novel antidepressant.

PMID- 23548604
TI  - Increase ICAM-1 and LFA-1 expression by cerebrospinal fluid of subarachnoid
      hemorrhage patients: involvement of TNF-alpha.
AB  - Subarachnoid hemorrhage (SAH) is a frequent occurrence in cerebrovascular
      accidents, and inflammation occurs in the subarachnoid space after SAH. Arachnoid
      cells have the capability to present antigens and active T-lymphocytes after
      stimulation by cerebrospinal fluid (CSF). However, the effect of CSF on T
      lymphocytes and arachnoid cell adhesion was not clearly understood. In this
      study, we used ELISA to detected tumor necrosis factor-alpha (TNF-alpha) content
      in CSF of SAH patients. CSF or recombinant TNF-alpha were applied on arachnoid
      cells and T-lymphoctes, and RT-PCR and western blotting were performed to
      determine the expression of intercellular adhesion molecule-1 (ICAM-1) in
      arachnoid cells and Lymphocyte Function-Associated Antigen-1 (LFA-1) in T
      lymphocytes, respectively. Meanwhile, the Matrix Metal Proteinase-9 (MMP-9)
      expression in these cells was also determined. We found that the content of TNF
      alpha in the CSF was significantly increased in the CSF of SAH patients (from 22
      +/- 8 pg/mL of healthy people to 436-450 pg/mL of SAH patients). Treatement with
      CSF could increase the expression of ICAM-1 in arachnoid cells and that of LFA-1
      in T-lymphocytes, mainly through the increased levels of TNF-alpha. We also found
      that the co-culture of arachnoid cells and T-lymphocytes increased the expression
      of MMP-9 in both cells through the interaction of ICAM-1 of and LFA-1. All of
      these results suggested that arachnoid cells are involved in the T-lymphocytes
      invasion in the subarachnoid space after SAH.

PMID- 23548606
TI  - The placenta in toxicology. Part I: Animal models in toxicology: placental
      morphology and tolerance molecules in the cynomolgus monkey (Macaca
      fascicularis).
AB  - The immune system represents a key defense mechanism against potential pathogens
      and adverse non-self materials. During pregnancy, the placenta is the point of
      contact between the maternal organism and non-self proteins of the fetal
      allograft and hence undoubtedly fulfils immune functions. In the placenta
      bacteria, foreign (non-self) proteins and proteins that might be introduced in
      toxicological studies or by medication are barred from reaching the progeny, and
      the maternal immune system is primed for acceptance of non-maternal fetal
      protein. Both immunologic protection of the fetus and acceptance of the fetus by
      the mother require effective mechanisms to prevent an immunologic fetomaternal
      conflict and to keep both organisms in balance. This is why the placenta requires
      toxicological consideration in view of its immune organ function. The following
      articles deal with placenta immune-, control-, and tolerance mechanisms in view
      of both fetal and maternal aspects. Furthermore, models for experimental access
      to placental immune function are addressed and the pathological evaluation is
      elucidated. "The Placenta as an Immune Organ and Its Relevance in Toxicological
      Studies" was subject of a continuing education course at the 2012 Society of
      Toxicologic Pathology meeting held in Boston, MA. 

PMID- 23548605
TI  - The placenta in toxicology. Part IV: Battery of toxicological test systems based
      on human placenta.
AB  - This review summarizes the potential and also some limitations of using human
      placentas, or placental cells and structures for toxicology testing. The placenta
      contains a wide spectrum of cell types and tissues, such as trophoblast cells,
      immune cells, fibroblasts, stem cells, endothelial cells, vessels, glands,
      membranes, and many others. It may be expected that in many cases the relevance
      of results obtained from human placenta will be higher than those from animal
      models due to species specificity of metabolism and placental structure. For
      practical and economical reasons, we propose to apply a battery of sequential
      experiments for analysis of potential toxicants. This should start with using
      cell lines, followed by testing placenta tissue explants and isolated placenta
      cells, and finally by application of single and dual side ex vivo placenta
      perfusion. With each of these steps, the relative workload increases while the
      number of feasible repeats decreases. Simultaneously, the predictive power
      enhances by increasing similarity with in vivo human conditions. Toxic effects
      may be detected by performing proliferation, vitality and cell death assays,
      analysis of protein and hormone expression, immunohistochemistry or testing
      functionality of signaling pathways, gene expression, transport mechanisms, and
      so on. When toxic effects appear at any step, the subsequent assays may be
      cancelled. Such a system may be useful to reduce costs and increase specificity
      in testing questionable toxicants. Nonetheless, it requires further
      standardization and end point definitions for better comparability of results
      from different toxicants and to estimate the respective in vivo translatability
      and predictive value. 

PMID- 23548607
TI  - Comparison of cochlear cell death caused by cisplatin, alone and in combination
      with furosemide.
AB  - Establishment of appropriate animal models is an important step in exploring the
      mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs
      we compared cochlear lesions induced by cisplatin administered in two regimens:
      consecutive application alone and in combination with furosemide. The effects of
      furosemide alone were also evaluated; it was found to cause temporary hearing
      loss and reversible damage to the stria vascularis. Consecutive application of
      cisplatin alone appeared to be disadvantageous because it resulted in progressive
      body weight loss and higher mortality compared to the combined regimen, which
      used a smaller cisplatin dose. The combined regimen resulted in comparable
      hearing loss and hair cell loss but a markedly lower mortality. However, their
      coadministration failed to cause similar damage to spiral ganglion neurons (SGN),
      as seen in animals that received cisplatin alone. This difference suggests that
      the combined regimen did not mimic the damage to cochlear neuronal innervation
      caused by the clinical application of cisplatin. The difference also suggests
      that the SGN lesion is not caused by cisplatin entering the cochlea via the stria
      vascularis. 

PMID- 23548608
TI  - Phenotype and secretory responses to oxidative stress in microglia.
AB  - The neonatal brain is particularly susceptible to oxidative stress. Our group has
      previously shown that following hypoxic-ischemic injury, hydrogen peroxide (H2O2)
      levels rise significantly particularly in the neonatal brain and are sustained
      for up to 7 days. This rapidly accumulated H2O2 is detrimental in the iron-rich
      immature brain as it can lead to the generation of dangerous free radicals that
      can cause extensive injury. To date, there is limited literature on the effects
      of increased H2O2 levels on microglial cells, which have been extensively
      implicated in the ensuing inflammatory injury. Microglial cultures were derived
      from the P1 mouse brain and exposed to either bolus concentrations of H2O2 (15 or
      50 MUM) or varying concentrations of continuous exposure for 4, 18 or 24 h.
      Continuous exposure of microglia to H2O2 was generated using the glucose oxidase
      catalase system generating levels of H2O2 <10 MUM. Reactive oxygen species and
      nitric oxide expression were measured. Conditioned medium was collected and
      analyzed for secreted cytokine levels. Treated cell extracts were processed for
      glutathione (oxidized and reduced) content and fixed cells were labeled for M1
      and M2a phenotype markers. Overall, it is evident that microglial exposure to
      continuous H2O2 has pleiotropic and biphasic effects. Continuous exposure to very
      low levels of H2O2 is more damaging to cell survival than higher bolus doses at
      18 h, and can produce considerably high levels of pro- and anti-inflammatory
      cytokines by 18 h. Significantly high levels of various chemokines/chemotactic
      molecules such as G-CSF, MIP-1b and MIP-2 are also produced in response to
      continuous low-dose H2O2 by 18 h. Interestingly, no prominent cytokine responses
      were seen with bolus treatment at any of the time points studied. H2O2 exposure
      promotes an M2a microglial phenotype in the absence of IL-4/IL-13 signaling,
      suggesting a wound-healing role for microglia and a delayed activation mechanism
      for H2O2 after such an insult. Together, these specific effects can be used to
      clarify the microglial cell responses following injury in the immature brain. 

PMID- 23548609
TI  - Quality control of house dust mite extracts for allergen immunotherapy.

PMID- 23548610
TI  - Using a novel coculture model to dissect the role of intramuscular lipid load on
      skeletal muscle insulin responsiveness under reduced estrogen conditions.
AB  - Reductions in estrogen function lead to adiposity and peripheral insulin
      resistance. Significant metabolic changes have been found in adipocytes and
      skeletal muscle with disruptions in the estrogen-signaling axis; however, it is
      unclear if intercellular communication exists between these tissues. The purpose
      of this study was to examine the impact of isolated adipocytes cocultured with
      single adult skeletal muscle fibers (SMF) collected from control female (SHAM)
      and ovariectomized female (OVX) mice. In addition, a second purpose was to
      compare differential effects of primary adipocytes from omental and inguinal
      adipose depots on SMF from these same groups. OVX SMF displayed greater lipid
      content, impaired insulin signaling, and lower insulin-induced glucose uptake
      compared with SHAM SMF without coculture. In the SHAM group, regardless of the
      adipose depot of origin, coculture induced greater intracellular lipid content
      compared with control SHAM SMF. The increased lipid in the SMF was associated
      with impaired insulin-induced glucose uptake when adipocytes were of omental, but
      not inguinal, origin. Coculture of OVX SMF with omental or inguinal adipocytes
      resulted in higher lipid content but no further reduction in insulin-induced
      glucose uptake compared with control OVX SMF. The data indicate that, in the OVX
      condition, there is a threshold for lipid accumulation in skeletal muscle beyond
      which there is no further impairment in insulin responsiveness. These results
      also demonstrate depot-specific effects of adipocyte exposure on skeletal muscle
      glucose uptake and further implicate a role for increased intracellular lipid
      storage in the pathogenesis of insulin resistance when estrogen levels are
      reduced.

PMID- 23548611
TI  - Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse
      liver.
AB  - CYP2E1 is of paramount toxicological significance because it metabolically
      activates a large number of low-molecular-weight toxicants and carcinogens. In
      this context, factors that interfere with Cyp2e1 regulation may critically affect
      xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate
      the role of female steroid hormones in the regulation of CYP2E1, as estrogens and
      progesterone are the bases of contraceptives and hormonal replacement therapy in
      menopausal women. Interestingly, a fluctuation in the hepatic expression pattern
      of Cyp2e1 was revealed in the different phases of the estrous cycle of female
      mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME),
      highly correlated with that in plasma gonadal hormone levels. Depletion of sex
      steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those
      detected in males and cyclic females at ME. Hormonal supplementation brought
      Cyp2e1 expression back to levels detected at E. The role of progesterone appeared
      to be more prominent than that of 17beta-estradiol. Progesterone-induced Cyp2e1
      upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1
      signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression
      potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways.
      The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly
      correlated with those observed in Hnf-1alpha, beta-catenin, and Srebp-1c. In
      conclusion, female steroid hormones are clearly involved in the regulation of
      CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic
      agents, conditions that may trigger several pathologies or exacerbate the
      outcomes of various pathophysiological states.

PMID- 23548612
TI  - Ceramide 1-phosphate induces macrophage chemoattractant protein-1 release:
      involvement in ceramide 1-phosphate-stimulated cell migration.
AB  - The bioactive sphingolipid ceramide 1-phosphate (C1P) is implicated in
      inflammatory responses and was recently shown to promote cell migration. However,
      the mechanisms involved in these actions are poorly described. Using J774A.1
      macrophages, we have now discovered a new biological activity of C1P: stimulation
      of monocyte chemoattractant protein-1 (MCP-1) release. This novel effect of C1P
      was pertussis toxin (PTX) sensitive, suggesting the intervention of Gi protein
      coupled receptors. Treatment of the macrophages with C1P caused activation of the
      phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase kinase
      (MEK)/extracellularly regulated kinases (ERK), and p38 pathways. Inhibition of
      these kinases using selective inhibitors or specific siRNA blocked the
      stimulation of MCP-1 release by C1P. C1P stimulated nuclear factor-kappaB
      activity, and blockade of this transcription factor also resulted in complete
      inhibition of MCP-1 release. Also, C1P stimulated MCP-1 release and cell
      migration in human THP-1 monocytes and 3T3-L1 preadipocytes. A key observation
      was that sequestration of MCP-1 with a neutralizing antibody or treatment with
      MCP-1 siRNA abolished C1P-stimulated cell migration. Also, inhibition of the
      pathways involved in C1P-stimulated MCP-1 release completely blocked the
      stimulation of cell migration by C1P. It can be concluded that C1P promotes MCP-1
      release in different cell types and that this chemokine is a major mediator of
      C1P-stimulated cell migration. The PI3K/Akt, MEK/ERK, and p38 pathways are
      important downstream effectors in this action.

PMID- 23548613
TI  - Kisspeptin inhibits a slow afterhyperpolarization current via protein kinase C
      and reduces spike frequency adaptation in GnRH neurons.
AB  - Kisspeptin signaling via its cognate receptor G protein-coupled receptor 54
      (GPR54) in gonadotropin-releasing hormone (GnRH) neurons plays a critical role in
      regulating pituitary secretion of luteinizing hormone and thus reproductive
      function. GPR54 is G(q)-coupled to activation of phospholipase C and multiple
      second messenger signaling pathways. Previous studies have shown that kisspeptin
      potently depolarizes GnRH neurons through the activation of canonical transient
      receptor potential channels and inhibition of inwardly rectifying K(+) channels
      to generate sustained firing. Since the initial studies showing that kisspeptin
      has prolonged effects, the question has been why is there very little spike
      frequency adaption during sustained firing? Presently, we have discovered that
      kisspeptin reduces spike frequency adaptation and prolongs firing via the
      inhibition of a calcium-activated slow afterhyperpolarization current (I(sAHP)).
      GnRH neurons expressed two distinct I(sAHP), a kisspeptin-sensitive and an apamin
      sensitive I(sAHP). Essentially, kisspeptin inhibited 50% of the I(sAHP) and
      apamin inhibited the other 50% of the current. Furthermore, the kisspeptin
      mediated inhibition of I(sAHP) was abrogated by the protein kinase C (PKC)
      inhibitor calphostin C, and the PKC activator phorbol 12,13-dibutyrate mimicked
      and occluded any further effects of kisspeptin on I(sAHP). The protein kinase A
      (PKA) inhibitors H-89 and the Rp diastereomer of adenosine 3',5'-cyclic
      monophosphorothioate had no effect on the kisspeptin-mediated inhibition but were
      able to abrogate the inhibitory effects of forskolin on the I(sAHP), suggesting
      that PKA is not involved. Therefore, in addition to increasing the firing rate
      through an overt depolarization, kisspeptin can also facilitate sustained firing
      through inhibiting an apamin-insensitive I(sAHP) in GnRH neurons via a PKC.

PMID- 23548614
TI  - Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet
      induced obesity.
AB  - A hallmark of brain injury from infection, vascular, neurodegenerative, and other
      disorders is the development of gliosis, which can be detected by magnetic
      resonance imaging (MRI). In rodent models of diet-induced obesity (DIO), high-fat
      diet (HFD) consumption rapidly induces inflammation and gliosis in energy
      regulating regions of the mediobasal hypothalamus (MBH), and recently we reported
      MRI findings suggestive of MBH gliosis in obese humans. Thus, noninvasive imaging
      may obviate the need to assess MBH gliosis using histopathological end points, an
      obvious limitation to human studies. To investigate whether quantitative MRI is a
      valid tool with which to measure MBH gliosis, we performed analyses, including
      measurement of T(2) relaxation time from high-field MR brain imaging of mice fed
      HFD and chow-fed controls. Mean bilateral T(2) relaxation time was prolonged
      significantly in the MBH, but not in the thalamus or cortex, of HFD-fed mice
      compared with chow-fed controls. Histological analysis confirmed evidence of
      increased astrocytosis and microglial accumulation in the MBH of HFD-fed mice
      compared with controls, and T(2) relaxation times in the right MBH correlated
      positively with mean intensity of glial fibrillary acidic protein staining (a
      marker of astrocytes) in HFD-fed animals. Our findings indicate that T(2)
      relaxation time obtained from high-field MRI is a useful noninvasive measurement
      of HFD-induced gliosis in the mouse hypothalamus with potential for translation
      to human studies.

PMID- 23548615
TI  - Menopause is associated with decreased whole body fat oxidation during exercise.
AB  - The purpose of this study was to examine if fat oxidation was affected by
      menopausal status and to investigate if this could be related to the oxidative
      capacity of skeletal muscle. Forty-one healthy women were enrolled in this cross
      sectional study [premenopausal (n = 19), perimenopausal (n = 8), and
      postmenopausal (n = 14)]. Estimated insulin sensitivity was obtained from an oral
      glucose tolerance test. Body composition was measured by dual-energy X-ray
      absorptiometry and magnetic resonance imaging. Fat oxidation and energy
      expenditure were measured during an acute exercise bout of 45 min of ergometer
      biking at 50% of maximal oxygen consumption (Vo2 max). Muscle biopsies from the
      vastus lateralis of the quadriceps muscle were obtained before and immediately
      after the exercise bout. Postmenopausal women had 33% [confidence interval (CI)
      95%: 12-55] lower whole body fat oxidation (P = 0.005) and 19% (CI 95%: 9-22)
      lower energy expenditure (P = 0.02) during exercise, as well as 4.28 kg lower
      lean body mass (LBM) than premenopausal women. Correction for LBM reduced
      differences in fat oxidation to 23% (P = 0.05), whereas differences in energy
      expenditure disappeared (P = 0.22). No differences between groups were found in
      mRNA [carnitine palmitoyltransferase I, beta-hydroxyacyl-CoA dehydrogenase (beta
      HAD), peroxisome proliferator-activated receptor-alpha, citrate synthase (CS),
      pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PGC-1alpha)], protein [phosphorylated AMP-activated protein
      kinase (AMPK), vascular endothelial growth factor, pyruvate dehydrogenase
      1Ealpha, cytochrome oxidase I], or enzyme activities (beta-HAD, CS) in resting
      skeletal muscle, except for an increased protein level of cytochrome c in the
      post- and perimenopausal women relative to premenopausal women. Postmenopausal
      women demonstrated a trend to a blunted exercise-induced increase in
      phosphorylation of AMPK compared with premenopausal women (P = 0.06). We conclude
      that reduced whole body fat oxidation after menopause is associated with reduced
      LBM.

PMID- 23548617
TI  - Factors affecting corneoscleral topography.
AB  - PURPOSE: To evaluate factors affecting corneoscleral profile (CSP) using anterior
      segment optical coherence tomography (AS-OCT) in combination with conventional
      videokeratoscopy. METHODS: OCT DATA WERE COLLECTED FROM 204 SUBJECTS OF MEAN AGE
      34.9 YEARS (SD: +/-15.2 years, range 18-65) using the Zeiss Visante AS-OCT and
      Medmont M300 corneal topographer. Measurements of corneal diameter (CD), corneal
      sagittal height (CS), iris diameter (ID), corneoscleral junction angle (CSJ), and
      scleral radius (SR) were extracted from multiple OCT images. Horizontal visible
      iris diameter (HVID) and vertical palpebral aperture (PA) were measured using a
      slit lamp graticule. Subject body height was also measured. Associations were
      then sought between CSP variables and age, height, ethnicity, sex, and refractive
      error. RESULTS: Significant correlations were found between age and ocular
      topography variables of HVID, PA, CSJ, SR, and ID (P < 0.0001), while height
      correlated with HVID, CD, and ID, and power vector terms with vertical plane
      keratometry, CD, and CS. Significant differences were noted between ethnicities
      with respect to CD (P = 0.0046), horizontal and vertical CS (P = 0.0068 and P =
      0.0095), and horizontal ID (P = 0.0010). The same variables, with the exception
      of vertical CS, also varied with sex; horizontal CD (P = 0.0018), horizontal CS
      (P = 0.0018), and ID (P = 0.0012). Age accounted for the greatest variance in
      topography variables (36%). CONCLUSIONS: Age is the main factor influencing CSP;
      this should be taken into consideration in contact lens design, IOL selection,
      and in the optimization of surgical procedures. Ocular topography also varied
      with height, sex, ethnicity, and refractive error.

PMID- 23548619
TI  - Optimizing Chinese character displays improves recognition and reading
      performance of simulated irregular phosphene maps.
AB  - PURPOSE: A visual prosthesis may elicit an irregular phosphene map relative to a
      regular electrode array. This study used simulated irregular phosphene maps as a
      way of optimizing the display methods of Chinese characters (CCs) to improve
      recognition and reading performance. METHODS: TWENTY SUBJECTS WITH NORMAL OR
      CORRECTED SIGHT PARTICIPATED IN TWO EXPERIMENTS (9 FEMALES, 11 MALES, 2030 YEARS
      OF AGE). EXPERIMENT 1: two character display methods were proposed: selecting
      phosphenes covered by character strokes on a simulated phosphene array
      (projection method) and finding the phosphene closest to the expected location in
      some range of an irregular phosphene array as a substitute (nearest neighbor
      search [NNS] method). The recognition accuracy of CCs was investigated using six
      levels for the coverage ratio of stroke and phosphene area and for search range,
      respectively, for two methods, for several irregularity levels. Experiment 2:
      reading accuracy (RA) and reading efficiency (RE) were measured using the regular
      array correspondence and NNS methods. RESULTS: EXPERIMENT 1: projection and NNS
      methods were significantly affected by coverage ratio or search range. NNS
      significantly improved CC recognition accuracy to the highest at 81.3 +/- 2.7%
      and 59.1 +/- 5.2%, respectively, for different irregularity levels, compared with
      the projection method. Experiment 2: RA and RE significantly decreased as the
      distortion level increased; NNS significantly improved RA (from approximately 40%
      to >80%) and RE (from approximately 13 char/min to >40 char/min) when reading
      more irregular paragraphs. CONCLUSIONS: The performance of CC recognition and
      paragraph reading when using an irregular phosphene array can be improved through
      optimizing the display method.

PMID- 23548618
TI  - Pseudomonas aeruginosa small protease (PASP), a keratitis virulence factor.
AB  - PURPOSE: The virulence contribution of Pseudomonas aeruginosa small protease
      (PASP) during experimental keratitis was studied by comparing a PASP-deficient
      mutant with its parent and rescue strains. METHODS: The pasP gene of P.
      aeruginosa was replaced with the tetracycline resistance gene via allelic
      exchange. A plasmid carrying the pasP gene was introduced into the PASP-deficient
      mutant to construct a rescue strain. The PASP protein in the culture supernatants
      was determined by Western blot analysis. Corneal virulence was evaluated in
      rabbit and mouse keratitis models by slit lamp examination (SLE), bacterial
      enumeration, and/or histopathological analysis. Various host proteins and the
      rabbit tear film were analyzed for their susceptibility to PASP degradation.
      RESULTS: The PASP-deficient mutant produced a significantly lower mean SLE score
      when compared with the parent or rescue strain (P <= 0.03) at 29 hours
      postinfection (PI). All of the strains grew equally in the rabbit cornea (P =
      0.971). Corneas infected with the PASP-deficient mutant showed moderate
      histopathology compared with those infected with the parent or rescue strain,
      which produced severe pathology inclusive of epithelial erosions, corneal edema,
      and neutrophil infiltration. In the mouse model, eyes inoculated with the PASP
      deficient mutant had a significantly lower mean SLE score at 24 hours PI than the
      eyes inoculated with the parent or rescue strain (P <= 0.007). PASP was found to
      degrade complement C3, fibrinogen, antimicrobial peptide LL-37, and constituents
      of the tear film. CONCLUSIONS: PASP is a commonly secreted protease of P.
      aeruginosa that contributes significantly to the pathogenesis of keratitis.

PMID- 23548620
TI  - Dual cognitive task affects reaching and grasping behavior in subjects with
      macular disorders.
AB  - PURPOSE: Subjects with macular disorders need longer time to plan and execute a
      reaching and grasping task compared with normally sighted controls. In everyday
      life it is normal to perform reaching and grasping movements while simultaneously
      carrying out a cognitively demanding task. We investigated whether a simultaneous
      "counting task" further affects the ability to reach and grasp an object in
      subjects with visual impairment (VI). As the visually guided action is considered
      to be solely under the control of the automatic parieto-premotor pathway, we
      hypothesize that there will be minimal effect of the counting task, needing
      working memory and attention, which is mediated by other pathways, on the
      performance of the reaching and grasping tasks. METHODS: Fourteen subjects with
      VI and 14 age-matched controls reached out and grasped a target while carrying
      out a counting task ("easy," "difficult," "no count"). A motion analysis system
      recorded and reconstructed the 3D hand and finger movements. RESULTS: Significant
      differences (P < 0.05) occurred for various indices between the two visual
      groups. Significant interaction effects occurred between the two groups for
      "onset time," "time after maximum grip," and "time after maximum velocity,"
      indicating that the dual task affects both the planning of the movement and the
      ability to carry out "online corrections." CONCLUSIONS: In both groups, the onset
      time was affected by the counting task, which requires attention and working
      memory. In VI subjects, the dual task affected "online corrections," suggesting
      that visually guided movements are not solely under the control of automatic
      processes.

PMID- 23548616
TI  - Role of androgen and vitamin D receptors in endothelial cells from benign and
      malignant human prostate.
AB  - Forty years ago, Judah Folkman (Folkman. N Engl J Med 285: 1182-1186, 1971)
      proposed that tumor growth might be controlled by limiting formation of new blood
      vessels (angiogenesis) needed to supply a growing tumor with oxygen and
      nutrients. To this end, numerous "antiangiogenic" agents have been developed and
      tested for therapeutic efficacy in cancer patients, including prostate cancer
      (CaP) patients, with limited success. Despite the lack of clinical efficacy of
      lead anti-angiogenic therapeutics in CaP patients, recent published evidence
      continues to support the idea that prostate tumor vasculature provides a
      reasonable target for development of new therapeutics. Particularly relevant to
      antiangiogenic therapies targeted to the prostate is the observation that
      specific hormones can affect the survival and vascular function of prostate
      endothelial cells within normal and malignant prostate tissues. Here, we review
      the evidence demonstrating that both androgen(s) and vitamin D significantly
      impact the growth and survival of endothelial cells residing within prostate
      cancer and that systemic changes in circulating androgen or vitamin D drastically
      affect blood flow and vascularity of prostate tissue. Furthermore, recent
      evidence will be discussed about the expression of the receptors for both
      androgen and vitamin D in prostate endothelial cells that argues for direct
      effects of these hormone-activated receptors on the biology of endothelial cells.
      Based on this literature, we propose that prostate tumor vasculature represents
      an unexplored target for modulation of tumor growth. A better understanding of
      androgen and vitamin D effects on prostate endothelial cells will support
      development of more effective angiogenesis-targeting therapeutics for CaP
      patients.

PMID- 23548621
TI  - Effects of thailanstatins on glucocorticoid response in trabecular meshwork and
      steroid-induced glaucoma.
AB  - PURPOSE: Elevated intraocular pressure (IOP) is a major risk factor in glaucoma.
      Various changes in the trabecular meshwork (TM) are responsible for elevated IOP.
      Glucocorticoids (GCs) increase IOP and mediate biochemical changes in the TM,
      similar to those associated with primary open-angle glaucoma (POAG). There are
      differences in steroid responsiveness among the population. Approximately 40% of
      individuals significantly elevate IOP (i.e., responders) upon GC administration,
      while others do not (i.e., nonresponders). The responders are at higher risk of
      developing POAG compared to the nonresponders. In addition, almost all POAG
      patients are steroid responders. GC responsiveness is regulated by the relative
      levels of the active GC receptor alpha (GRalpha) and the alternatively spliced
      dominant negative regulator isoform GRbeta. Glaucomatous TM cell strains have a
      lower GRbeta-GRalpha ratio compared to normal TM cells, making them more
      sensitive to GCs. Our purpose was to investigate the role of a special class of
      natural products called thailanstatins (TSTs) in GR alternative splicing and GC
      response in cultured human TM cells. METHODS: Quantitative RT-PCR and Western
      immunoblotting were used to study the effect of TSTs on GRbeta-GRalpha ratios in
      human TM cell strains. Effects of TSTs on dexamethasone (DEX) responsiveness were
      assessed by GRE-luciferase reporter activity assay and fibronectin (FN) induction
      in TM cells. RESULTS: TSTs increased the GRbeta-GRalpha ratio in TM cells.
      Increased GRbeta-GRalpha ratios were associated with decreased DEX-mediated FN
      induction and GRE-luciferase activity. CONCLUSIONS: TSTs modulate the GR splicing
      process to enhance GRbeta levels and thereby decrease the GC response in cultured
      human TM cells. These TSTs, or similar compounds, may potentially be new glaucoma
      therapeutic agents.

PMID- 23548622
TI  - Treatment of geographic atrophy with subconjunctival sirolimus: results of a
      phase I/II clinical trial.
AB  - PURPOSE: To investigate the safety and effects of subconjunctival sirolimus, an
      mTOR inhibitor and immunosuppressive agent, for the treatment of geographic
      atrophy (GA). METHODS: The study was a single-center, open-label phase II trial,
      enrolling 11 participants with bilateral GA; eight participants completed 24
      months of follow-up. Sirolimus (440 MUg) was administered every 3 months as a
      subconjunctival injection in only one randomly assigned eye in each participant
      for 24 months. Fellow eyes served as untreated controls. The primary efficacy
      outcome measure was the change in the total GA area at 24 months. Secondary
      outcomes included changes in visual acuity, macular sensitivity, central retinal
      thickness, and total drusen area. RESULTS: The study drug was well tolerated with
      few symptoms and related adverse events. Study treatment in study eyes was not
      associated with structural or functional benefits relative to the control fellow
      eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow
      eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0
      letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03).
      Substantial differences in mean changes in drusen area, central retinal
      thickness, and macular sensitivity were not detected for all analysis time points
      up to 24 months. CONCLUSIONS: Repeated subconjunctival sirolimus was well
      tolerated in patients with GA, although no positive anatomic or functional
      effects were identified. Subconjunctival sirolimus may not be beneficial in the
      prevention of GA progression, and may potentially be associated with effects
      detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).

PMID- 23548623
TI  - Quantitative fundus autofluorescence in mice: correlation with HPLC quantitation
      of RPE lipofuscin and measurement of retina outer nuclear layer thickness.
AB  - PURPOSE: Our study was conducted to establish procedures and protocols for
      quantitative autofluorescence (qAF) measurements in mice, and to report changes
      in qAF, A2E bisretinoid concentration, and outer nuclear layer (ONL) thickness in
      mice of different genotypes and age. METHODS: Fundus autofluorescence (AF) images
      (55 degrees  lens, 488 nm excitation) were acquired in albino Abca4(-/-),
      Abca4(+/-), and Abca4(+/+) mice (ages 2-12 months) with a confocal scanning laser
      ophthalmoscope (cSLO). Gray levels (GLs) in each image were calibrated to an
      internal fluorescence reference. The bisretinoid A2E was measured by quantitative
      high performance liquid chromatography (HPLC). Histometric analysis of ONL
      thicknesses was performed. RESULTS: The Bland-Altman coefficient of repeatability
      (95% confidence interval) was +/-18% for between-session qAF measurements. Mean
      qAF values increased with age (2-12 months) in all groups of mice. qAF was
      approximately 2-fold higher in Abca4(-/-) mice than in Abca4(+/+) mice and
      approximately 20% higher in heterozygous mice. HPLC measurements of the
      lipofuscin fluorophore A2E also revealed age-associated increases, and the fold
      difference between Abca4(-/-) and wild-type mice was more pronounced
      (approximately 3-4-fold) than measurable by qAF. Moreover, A2E levels declined
      after 8 months of age, a change not observed with qAF. The decline in A2E levels
      in the Abca4(-/-) mice corresponded to reduced photoreceptor cell viability as
      reflected in ONL thinning beginning at 8 months of age. CONCLUSIONS: The qAF
      method enables measurement of in vivo lipofuscin and the detection of genotype
      and age-associated differences. The use of this approach has the potential to aid
      in understanding retinal disease processes and will facilitate preclinical
      studies.

PMID- 23548625
TI  - The right colon--a real challenge for the endoscopist.

PMID- 23548624
TI  - FIH-1/c-kit signaling: a novel contributor to corneal epithelial glycogen
      metabolism.
AB  - PURPOSE: Corneal epithelial cells have large stores of glycogen, which serve as
      their primary energy source. Recently, we demonstrated that factor-inhibiting
      hypoxia-inducible factor 1 (FIH-1) diminished glycogen stores in vitro and in
      vivo, working through the Akt/Glycogen Synthase Kinase (GSK)-3beta pathway. In
      this study we investigated the relationship between FIH-1 and c-kit as it
      pertains to limbal and corneal epithelial glycogen stores. METHODS: Limbal and
      corneal epithelia from wild-type FIH-1(-/-) and Kit(W/Wv) mice were stained with
      periodic acid Schiff (PAS) to detect glycogen. RNA samples prepared from laser
      capture microdissected populations of limbal epithelium were subjected to real
      time quantitative PCR to determine c-kit ligand expression. Submerged cultures of
      primary human corneal epithelial keratinocytes (HCEKs) transduced with FIH-1 were
      treated with c-kit ligand to establish further a FIH-1/c-kit interaction via
      Western analysis. Akt phosphorylation was assessed by Western blotting. RESULTS:
      The limbal epithelial cells of FIH-1 null mice had an increase in glycogen levels
      as well as increased c-kit ligand mRNA compared with wild-type controls.
      Consistent with a FIH-1/c-kit association, the diminished Akt signaling observed
      in FIH-1-overexpressing HCEKs could be restored by the addition of c-kit ligand.
      Interestingly, Akt signaling and glycogen content of the corneal epithelium were
      significantly decreased in c-kit mutant mice. CONCLUSIONS: c-Kit signaling has
      been shown to affect glucose metabolism via the Akt/GSK-3beta pathway. An inverse
      relationship between FIH-1 and c-kit signaling pathways accounts, in part, for
      differences in glycogen content between corneal and limbal epithelial cells.

PMID- 23548626
TI  - Plasma cell neoplasms showing multilobulated nuclei.

PMID- 23548627
TI  - Fetoscopic diagnosis of congenital megalourethra at early second trimester.
AB  - Congenital megalourethra is a rare urogenital malformation that is usually
      associated with lower urinary tract obstruction. In association with hypoplasia
      or deficiency of the corpus spongiosa and/or corpus cavernosum, a cystic
      dilatation of penile urethra is generally observed. We present a case of
      congenital megalourethra diagnosed by fetoscopy and ultrasonography at 17 weeks
      of gestation. Fetoscopic investigation demonstrated a balloon dilatation of the
      penis with a complete obstruction of the urethral meatus, which could distinguish
      a fusiform type congenital megalourethra from other disorders. Autopsy subsequent
      to the termination of pregnancy revealed a complete deficit of both corpus
      spongiosa and corpus cavernosum. 

PMID- 23548628
TI  - Conformational investigation of antibiotic proximicin by X-ray structure analysis
      and quantum studies suggest a stretched conformation of this type of gamma
      peptide.
AB  - The proximicins A-C are naturally occurring cytotoxic gamma-peptides that contain
      the unique 4-amino-furan-carboxylic acid. In contrast to the structurally related
      cytotoxic natural DNA binder netropsin and distamycin, both exhibiting as core
      building block N-methyl-4-amino-pyrrol-carboxylic acid, no DNA binding was
      observed for the procimicins. X-ray analysis of crystals of a protected 4-amino
      furan-2-carboxylic acid dipeptide revealed a stretched conformation. In contrast,
      for netropsin and distamycin, sickle-shaped crystal conformations were observed.
      DFT-calculations elegantly confirm these conformational arrangements. The most
      stable conformers of the proximicins are linear whereas sickle-shaped
      conformations are less stable, having higher Gibbs energies. For netropsin,
      distamycin and the netropsin-proximicin-hybrid a sickle shaped conformation
      appears energetically favored. The reported results are consistent with the
      observations that the proximicins A-C do not bind to the DNA and have a different
      mode of action concerning their cytotoxic activity with respect to netropsin and
      distamycin.

PMID- 23548629
TI  - Conformational stability of triazolyl functionalized collagen triple helices.
AB  - Functionalized collagen is attractive for the development of synthetic
      biomaterials. Herein we present the functionalization of azidoproline containing
      collagen model peptides with various alkynes using click chemistry. The influence
      on the stability of the collagen triple helix of the stereochemistry of the
      introduced triazolyl prolines (4R or 4S), the position of their incorporation
      (Xaa or Yaa) and the substituents attached to them are shown. The results provide
      a useful guide for the optimal functionalization of collagen using click
      chemistry.

PMID- 23548630
TI  - The impact of altered gravity and vibration on endothelial cells during a
      parabolic flight.
AB  - BACKGROUND: Endothelial cells (EC) cultured under altered gravity conditions show
      a cytoskeletal disorganization and differential gene expression (short-term
      effects), as well as apoptosis in adherently growing EC or formation of tubular
      3D structures (long-term effects). METHODS: Investigating short-term effects of
      real microgravity, we exposed EC to parabolic flight maneuvers and analysed them
      on both protein and transcriptional level. The effects of hypergravity and
      vibration were studied separately. RESULTS: Pan-actin and tubulin proteins were
      elevated by vibration and down-regulated by hypergravity. beta-Actin was reduced
      by vibration. Moesin protein was reduced by both vibration and hypergravity,
      ezrin potein was strongly elevated under vibration. Gene expression of ACTB,
      CCND1, CDC6, CDKN1A, VEGFA, FLK-1, EZR, ITBG1, OPN, CASP3, CASP8, ANXA2, and
      BIRC5 was reduced under vibration. With the exception of CCNA2, CCND1, MSN, RDX,
      OPN, BIRC5, and ACTB all investigated genes were downregulated by hypergravity.
      After one parabola (P) CCNA2, CCND1, CDC6, CDKN1A, EZR, MSN, OPN, VEGFA, CASP3,
      CASP8, ANXA1, ANXA2, and BIRC5 were up-, while FLK1 was downregulated. EZR, MSN,
      OPN, ANXA2, and BIRC5 were upregulated after 31P. CONCLUSIONS: Genes of the
      cytoskeleton, angiogenesis, extracellular matrix, apoptosis, and cell cycle
      regulation were affected by parabolic flight maneuvers. We show that the
      microgravity stimulus is stronger than hypergravity/vibration.

PMID- 23548631
TI  - Silencing of ADIPOQ efficiently suppresses preadipocyte differentiation in
      porcine.
AB  - AIMS: Our study aims to characterize the functions of the ADIPOQ gene in the
      process of fat deposition of pigs, thereby providing a basis for the use of this
      gene as a molecular marker for pork quality. METHODS: We used healthy Junmu1
      piglets less than 7 days of age to establish an in vitro culture system for
      porcine preadipocytes. Chemically synthesized short hairpin RNAs (shRNA) were
      transfected into porcine preadipocytes to silence the expression of the ADIPOQ
      gene. We monitored preadipocyte differentiation and determined the levels of the
      adipocyte differentiation transcription factors lipoprotein lipase (LPL),
      peroxisome proliferator-activated receptor gamma (PPARgamma) and adipocyte fatty
      acid binding protein (AP2) mRNAs to investigate the effects of ADIPOQ on the
      differentiation of porcine preadipocytes. RESULTS: After transfection, the mRNA
      and protein levels of the ADIPOQ gene were significantly decreased (P < 0.01),
      the number of lipid droplets in the adipocytes was significantly reduced, the OD
      values reflecting the fat content were significantly decreased (P < 0.01), and
      the levels of LPL, PPARgamma and AP2 were significantly reduced (P < 0.01).
      CONCLUSIONS: These results suggest that interference with ADIPOQ gene expression
      can inhibit the differentiation of porcine preadipocytes.

PMID- 23548632
TI  - USP2-45 represses aldosterone mediated responses by decreasing mineralocorticoid
      receptor availability.
AB  - BACKGROUND/AIMS: Ligand activation of the mineralocorticoid receptor (MR) induces
      several post-translational modifications (PTMs). Among the different PTMs, MR is
      known to be dynamically ubiquitylated with impact on its stability and
      transcriptional activity. Previously, we have shown that MR is monoubiquitylated
      at the basal state and that aldosterone stimulation induces monoubiquitylation
      removal prompting polyubiquitin-dependent destabilization of the receptor and
      proteasomal degradation. This study investigated the role of the aldosterone
      induced ubiquitin-specific protease USP2-45 on the ubiquitylation state of MR.
      METHODS: Renal epithelial cells M1 were co-transfected with MR with or without
      wild-type or inactive USP2-45. The association of MR with USP2-45 or TSG101 as
      well as MR ubiquitylation state were determined by immunoprecipitation and
      immunoblotting. MR transcriptional activity was assessed via a luciferase
      reporter gene. RESULTS: We show that USP2-45 is able to bind MR and, similarly to
      aldosterone, induce MR monoubiquitylation removal, disruption of MR/TSG101
      association and destabilization of MR at protein level. CONCLUSION: This study
      provides a novel role for USP2-45 by playing a pivotal role in the regulation of
      the ubiquitylation state of MR and reveals the existence of a negative feedback
      loop for limiting the aldosterone induced response.

PMID- 23548633
TI  - Effect of hexavalent chromium on electron leakage of respiratory chain in
      mitochondria isolated from rat liver.
AB  - BACKGROUND/AIMS: In the present study, we explored reactive axygen species (ROS)
      production in mitochondria, the mechanism of hexavalent chromium (Cr(VI))
      hepatotoxicity, and the role of protection by GSH. METHODS: Intact mitochondria
      were isolated from rat liver tissues and mitochondrial basal respiratory rates of
      NADH and FADH2 respiratory chains were determined. Mitochondria were treated with
      Cr(VI), GSH and several complex inhibitors. Mitochondria energized by
      glutamate/malate were separately or jointly treated with Rotenone (Rot),
      diphenyleneiodonium (DPI) and antimycinA (Ant), while mitochondria energized by
      succinate were separately or jointly treated with Rot, DPI '
      thenoyltrifluoroacetone (TTFA) and Ant. RESULTS: Cr(VI) concentration-dependently
      induced ROS production in the NADH and FADH2 respiratory chain in liver
      mitochondria. Basal respiratory rate of the mitochondrial FADH2 respiratory chain
      was significantly higher than that of NADH respiratory chain. Hepatic
      mitochondrial electron leakage induced by Cr(VI) from NADH respiratory chain were
      mainly from ubiquinone binding sites of complex I and complex III. CONCLUSION:
      Treatment with 50uM Cr(VI) enhances forward movement of electrons through FADH2
      respiratory chain and leaking through the ubiquinone binding site of complex III.
      Moreover, the protective effect of GSH on liver mitochondria electron leakage is
      through removing excess H2O2 and reducing total ROS.

PMID- 23548634
TI  - Antioxidant compound supplementation prevents oxidative damage in a Drosophila
      model of Parkinson's disease.
AB  - Loss-of-function mutations in the DJ-1 gene are linked to rare autosomal
      recessive forms of parkinsonism. In Drosophila, two DJ-1 orthologs have been
      identified, DJ-1alpha and DJ-1beta. Several studies have shown that DJ-1beta
      mutant flies are viable and fertile but exhibit age-dependent locomotor defects,
      shortened life span, and enhanced sensitivity to toxins that induce oxidative
      stress response compared to control flies. We also demonstrated that long-term
      dietary supplementation with antioxidant compounds was effective at increasing
      life-span values of DJ-1beta mutants. These results, together with high levels of
      oxidative stress markers detected in newly eclosed DJ-1beta mutant flies compared
      to controls, led to the proposal that the life-span phenotype was in part due to
      defects in the oxidative stress response. To further demonstrate this assumption,
      we analyzed in detail several markers of oxidative stress in control and DJ-1beta
      mutant flies, either untreated or treated with antioxidant compounds. First, we
      quantified global reactive oxygen species (ROS) as well as H2O2 production; next
      we measured the activity of several enzymes that respond to oxidative stress such
      as catalase and superoxide dismutase; and finally we determined protein oxidative
      damage. Our results showed that DJ-1beta mutants exhibit elevated ROS production
      and protein oxidative damage as well as decreased antioxidant enzyme activity
      compared to control flies of the same age, which is consistent with the proposed
      protective role of DJ-1beta against oxidative stress. We found that
      supplementation with either alpha-tocopherol or the general antioxidant compound
      ascorbic acid (vitamin C) increased catalase activity and decreased H2O2 and
      oxidized protein levels in DJ-1beta mutants and control flies, but it led to
      decreased superoxide dismutase activity, maybe as a consequence of a global
      reduction in oxidative stress. However, alpha-tocopherol supplementation
      specifically reduced global ROS production in DJ-1beta mutant flies. This study
      confirms the important role of DJ-1beta in oxidative stress response in
      Drosophila, especially at the level of H2O2 detoxification, and provides evidence
      that early antioxidant supplementation is an effective treatment to suppress
      phenotypes in DJ-1beta mutants partly by reducing oxidative damage. 

PMID- 23548635
TI  - Oxaliplatin-induced oxidative stress in nervous system-derived cellular models:
      could it correlate with in vivo neuropathy?
AB  - Oxaliplatin is a platinum-organic drug with antineoplastic properties used for
      colorectal cancer. With respect to the other platinum derivates oxaliplatin
      induces only a mild hematological and gastrointestinal toxicity. Its limiting
      side effect is its neurotoxicity, which results in a sensory neuropathy. Repeated
      oxaliplatin treatment in the rat led to a neuropathic pain characterized by a
      significant oxidative damage throughout the nervous system. The natural
      antioxidants silibinin and alpha-tocopherol reduce redox alteration and prevent
      pain. Starting from the "oxidative hypothesis" as a molecular basis of
      chemotherapy-induced neurotoxicity, we decided to explore deep inside the
      mechanisms of oxaliplatin neurotoxicity and search for a cellular system useful
      for screening antioxidant compounds that can reduce oxaliplatin neurotoxicity.
      Focusing on various constituents of the central nervous system, we used the
      neuronal-derived cell line SH-SY5Y and primary cultures of rat cortical
      astrocytes. Oxaliplatin significantly increased superoxide anion production and
      induced lipid peroxidation (malonyldialdehyde levels) and protein (carbonylated
      proteins) and DNA oxidation (8-OH-dG levels). Silibinin and alpha-tocopherol
      (10uM) were able to reduce the oxidative damage in both cell types. These
      antioxidants fully protected astrocytes from the caspase 3 apoptotic signaling
      activation induced by oxaliplatin. The damage prevention effects of silibinin and
      alpha-tocopherol on nervous system-derived cells did not interfere with the
      oxaliplatin antineoplastic in vitro mechanism as evaluated on a human colon
      adenocarcinoma cell line (HT29). Moreover, neither silibinin nor alpha-tocopherol
      modified the oxaliplatin-induced apoptosis in HT29 cells, suggesting a different
      antiapoptotic profile in normal vs tumoral cells for these antioxidant compounds.
      In conclusion, because data obtained in in vitro cellular models parallel the in
      vivo study we propose cell models to investigate oxaliplatin neurotoxicity and to
      screen possible therapeutic adjuvant agents. 

PMID- 23548636
TI  - Curcumin maintains cardiac and mitochondrial function in chronic kidney disease.
AB  - Curcumin, a natural pigment with antioxidant activity obtained from turmeric and
      largely used in traditional medicine, is currently being studied in the
      chemoprevention of several diseases for its pleiotropic effects and nontoxicity.
      In chronic renal failure, the pathogenic mechanisms leading to cardiovascular
      disorders have been associated with increased oxidative stress, a process
      inevitably linked with mitochondrial dysfunction. Thus, in this study we aimed at
      investigating if curcumin pretreatment exerts cardioprotective effects in a rat
      model of subtotal nephrectomy (5/6Nx) and its impact on mitochondrial
      homeostasis. Curcumin was orally administered (120mg/kg) to Wistar rats 7 days
      before nephrectomy and after surgery for 60 days (5/6Nx+curc). Renal dysfunction
      was detected a few days after nephrectomy, whereas changes in cardiac function
      were observed until the end of the protocol. Our results indicate that curcumin
      treatment protects against pathological remodeling, diminishes ischemic events,
      and preserves cardiac function in uremic rats. Cardioprotection was related to
      diminished reactive oxygen species production, decreased oxidative stress
      markers, increased antioxidant response, and diminution of active
      metalloproteinase-2. We also observed that curcumin's cardioprotective effects
      were related to maintaining mitochondrial function. Aconitase activity was
      significantly higher in the 5/6Nx + curc (408.5+/-68.7nmol/min/mg protein) than
      in the 5/6Nx group (104.4+/-52.3nmol/min/mg protein, P<0.05), and mitochondria
      from curcumin-treated rats showed enhanced oxidative phosphorylation capacities
      with both NADH-linked substrates and succinate plus rotenone (3.6+/-1 vs 1.1+/
      0.9 and 3.1+/-0.7 vs 1.2+/-0.8, respectively, P<0.05). The mechanisms involved in
      cardioprotection included both direct antioxidant effects and indirect strategies
      that could be related to protein kinase C-activated downstream signaling.

PMID- 23548637
TI  - Effects of increasing diffusive sodium removal on blood pressure control in
      hemodialysis patients with optimal dry weight.
AB  - BACKGROUND: Sodium, apart from volume, may have an independent effect on blood
      pressure (BP) regulation. METHODS: Sixteen hypertensive hemodialysis patients
      were enrolled, who have achieved their dry weight assessed by bioimpedance
      methods, with pre-dialysis plasma sodium levels slightly higher than the facility
      dialysate sodium concentration 138 mmol/l. After a 1-month period of dialysis
      with standard dialysate sodium concentration of 138 mmol/l, the patients were
      followed up for a 4-month period with dialysate sodium set at 136 mmol/l.
      RESULTS: Along with lowering dialysate sodium, there were significant decreases (
      10 mm Hg and -6 mm Hg) in 44-hour ambulatory systolic and diastolic BP at 4
      months. Interdialytic weight gain adjusted to the estimated dry weight mildly but
      significantly decreased (4.81 +/- 1.51 vs. 4.36 +/- 1.37%, p = 0.047). The post
      dialysis volume parameters remained constant throughout the study period.
      CONCLUSION: In selected hypertensive hemodialysis patients with optimal dry
      weight, increasing diffusive sodium removal resulted in significant BP decrease.
      It was probably due to a volume-independent effect.

PMID- 23548638
TI  - Nucleation kinetics, growth and studies of beta-alanine single crystals.
AB  - Solubility and metastable zone width for the re-crystallized salt of beta-alanine
      was determined. Induction period measurement for the selected supersaturation
      ratios at room temperature (31  degrees C) was carried out for supersaturated
      aqueous solutions of beta-alanine and it is noticed that induction period
      decreases with increase of supersaturation ratio. The nucleation parameters such
      as Gibbs free energy change, radius and number of molecules of the critical
      nucleus, interfacial tension and the nucleation rate have been evaluated by
      classical nucleation theory. Single crystals of beta-alanine were grown using the
      optimized nucleation parameters by solution method and grown crystals have been
      subjected to various studies like XRD studies, FTIR, optical, thermal and SHG
      studies.

PMID- 23548639
TI  - Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively
      regulates downstream signaling.
AB  - The suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family of
      E3 ubiquitin ligases. SOCS2 is known to regulate signal transduction by cytokine
      receptors and receptor tyrosine kinases. The receptor tyrosine kinase FLT3 is of
      importance for proliferation, survival and differentiation of hematopoietic cells
      and is frequently mutated in acute myeloid leukemia. We observed that SOCS2
      associates with activated FLT3 through phosphotyrosine residues 589 and 919, and
      co-localizes with FLT3 in the cell membrane. SOCS2 increases FLT3 ubiquitination
      and accelerates receptor degradation in proteasomes. SOCS2 negatively regulates
      FLT3 signaling by blocking activation of Erk 1/2 and STAT5. Furthermore, SOCS2
      expression leads to a decrease in FLT3-ITD-mediated cell proliferation and colony
      formation. Thus, we suggest that SOCS2 associates with activated FLT3 and
      negatively regulates the FLT3 signaling pathways.

PMID- 23548640
TI  - Volume expansion does not alter cerebral tissue oxygen extraction in preterm
      infants with clinical signs of poor perfusion.
AB  - BACKGROUND: Preterm infants with signs of poor perfusion are often treated with
      volume expansion, although evidence regarding its effect on cerebral perfusion is
      lacking. Moreover, the effect is questionable in preterm infants with an adequate
      cerebrovascular autoregulation (CAR). A useful measure to assess perfusion is
      cerebral fractional tissue oxygen extraction (cFTOE). OBJECTIVES: To assess the
      effect of volume expansion on cFTOE in preterm infants with signs of poor
      perfusion. METHODS: In this observational study, we assessed cFTOE using near
      infrared spectroscopy in preterm infants with signs of poor perfusion before,
      during and 1 h after volume expansion treatment. Simultaneously, we measured mean
      arterial blood pressure (MABP). We tested the effect of volume expansion on both
      cFTOE and MABP, using multi-level analyses. We intended to define a subgroup that
      responded to volume expansion with an increase in blood pressure and a decrease
      in cFTOE, suggesting absent CAR. RESULTS: In 14 preterm infants, with a median
      gestational age of 26.7 weeks (25.0-28.7 weeks) and a median birth weight of 836
      g (615-1,290 g), we found a small increase in MABP during (1.4 +/- 1.4 mm Hg, p =
      0.003) and after (1.8 +/- 1.7 mm Hg, p = 0.001) volume expansion, but no change
      in cFTOE during (-0.19 +/- 0.1% p = 0.44) or after (-0.53 +/- 0.1% p = 0.34)
      volume expansion. We were unable to define a subgroup lacking CAR. CONCLUSIONS:
      Cerebral perfusion, as assessed by cFTOE, does not improve in preterm infants
      with signs of poor perfusion following volume expansion. In these infants, either
      CAR is present or volume expansion is inadequate to affect cFTOE.

PMID- 23548641
TI  - Self-assembled, functionalized graphene and DNA as a universal platform for
      colorimetric assays.
AB  - We have demonstrated a robust sensing strategy by employing single-stranded probe
      DNA and the hemin-graphene hybrid (GH) to detect a broad range of targets
      including metal ions, DNA and small molecules. This nearly "universal" biosensor
      approach is based on the DNA-mediated assembly of the hemin-graphene composite
      upon addition of the targets. Afterwards, GH aggregate resulting from DNA
      hybridization will occur. The DNA-GH hybrids will settle on the bottom of the
      vial after centrifugation, leaving behind a transparent supernatant. After
      incubation with TMB and H2O2, the colorimetric signal of the centrifugal
      supernatant will be significantly lower compared to that in the absence of
      targets. Therefore, mediation of the assembly of DNA on GH by targets can yield a
      facile means with tunable optical properties in response to concentration changes
      of the targets. This colorimetric "readout" offers great advantages such as the
      simple operation process, low-cost portable instrument and easy-to-use
      applications. Therefore, we believe that this method promises a great potential
      of becoming a routine tool for quantitative detection of a wide spectrum of
      analytes for specific applications in biodiagnostics, nanoelectronics, and
      bionanotechnology.

PMID- 23548642
TI  - Childhood neglect: exploring a short questionnaire in Poland and Germany.
AB  - BACKGROUND: Estimates about childhood abuse and neglect in various countries of
      the world indicate that cases of neglect outnumber cases of abuse by far.
      However, childhood neglect itself constitutes a neglected domain in psychological
      and medical research; far more articles have been published about abuse. SAMPLING
      AND METHODS: A ten-item questionnaire assessing childhood neglect was
      administered to two surveys in Poland (n = 508) and Germany (n = 500) via the
      internet. RESULTS: Internal consistency was high in both countries, i.e.
      Cronbach's alpha was 0.82 in Poland and 0.88 in Germany. No distinction could be
      made between physical and emotional neglect. Values for neglect were similar for
      Polish and German men, but German women reported more neglect than Polish women.
      CONCLUSIONS: The Neglect Questionnaire is suitable for research in both Poland
      and Germany.

PMID- 23548643
TI  - Real-time tissue elastography as promising diagnostic tool for diagnosis of lymph
      node metastases in patients with malignant melanoma: a prospective single-center
      experience.
AB  - BACKGROUND: Real-time tissue elastography is a new, noninvasive method in
      ultrasonography, differentiating tissues according to their stiffness. Earlier
      studies have highlighted this technique as a useful diagnostic tool for the
      detection of noncutaneous malignancies like breast, prostate and thyroid cancer
      based on the principle that tumor cells present a higher stiffness compared to
      the adjacent normal tissue. OBJECTIVE: The purpose of our study was to
      investigate the value of real-time tissue elastography for the differentiation of
      benign and metastatic peripheral lymph nodes (LN) in patients with cutaneous
      melanoma by comparing this technique with conventional B-mode sonography combined
      with power Doppler sonography (PDS). METHODS: In this prospective study, 36
      melanoma patients (23 females and 13 males, mean age 62.7 +/- 11.1 years)
      undergoing LN excision at the Department of Dermatology and Allergy, University
      of Bonn, were included between July 2011 and July 2012. Real-time tissue
      elastography was planned prior to surgery and histopathological examination.
      Elasticity images had been qualitatively scored for the proportion of stiff areas
      from pattern 1-5 (soft to stiff) on the basis of a newly defined system for LNs.
      RESULTS: A total of 42 LNs have been removed in 36 patients. Of these 42 LNs, 21
      carried melanoma cells and 21 were benign LNs. Significant differences in
      elastographic patterns were found between metastatic and nonmetastatic LNs. In
      real-time tissue elastography, 19 (90.5%) of 21 metastatic LNs showed a pattern
      of 3, 4 or 5. Of all benign LNs, 76.2% had a pattern of 1 or 2 in their
      elastogram. Sensitivity and specificity of B-mode sonography combined with PDS
      were 80.9 and 76.2%, respectively, 90.5 and 76.2% for elastography and 95.2 and
      76.2% for the combined evaluation. CONCLUSION: An elastography pattern >=3 was
      identified as an independent significant factor, predicting a metastatic LN
      involvement. The combination of elastography with conventional B-mode sonography
      has the potential to further improve the differentiation between benign and
      metastatic peripheral LNs in melanoma patients.

PMID- 23548644
TI  - Association between ozone exposure and onset of stroke in Allegheny County,
      Pennsylvania, USA, 1994-2000.
AB  - BACKGROUND: Epidemiological studies have shown adverse short-term effects of air
      pollution on health including cardiovascular morbidity and mortality. However,
      air pollution-related stroke has received less attention. METHODS: In this study,
      we performed a time-stratified case-crossover analysis to evaluate the
      relationships between stroke hospital admissions and O3, among patients aged 65
      years and older in Allegheny County, Pa., USA, between 1994 and 2000. We also
      examined whether the effects of air pollutants differed across strata defined by
      patient demographic characteristics and ambient temperature. RESULTS: Exposures
      to O3 on the current day increase the risk of total stroke hospitalization by
      1.9% (95% CI: 0.01-3.8) per interquartile range increase in concentration.
      Furthermore, the results suggest that males were more sensitive to adverse health
      effects of O3 on stroke hospitalization than females. CONCLUSION: These results
      suggest that O3 has an adverse effect on stroke hospitalization. Specific patient
      subgroups, such as males, may be at increased risk.

PMID- 23548645
TI  - Safety of new oral anticoagulants with dual antiplatelet therapy in patients with
      acute coronary syndromes.
AB  - OBJECTIVE: To determine the safety of dabigatran, rivaroxaban, or apixaban with
      dual antiplatelet therapy in patients with acute coronary syndromes. DATA
      SOURCES: A literature search of MEDLINE (1946-January 2013) was conducted, using
      the search terms dabigatran, rivaroxaban, or apixaban in combination with dual
      antiplatelet therapy. A search of literature citations was conducted to identify
      additional references. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled
      trials involving the use of one of the new anticoagulants with concomitant dual
      antiplatelet therapy were included in the review. DATA SYNTHESIS: Five randomized
      controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of
      rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients
      with a recent acute coronary syndrome, so most patients were receiving aspirin
      and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of
      one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of
      dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and
      clinically relevant nonmajor bleeding with increasing doses of the
      anticoagulants. The Phase 3 trial of apixaban was terminated early due to an
      excess of bleeding events, and the trial of rivaroxaban also found an increased
      risk of bleeding. CONCLUSIONS: The emerging use of dabigatran, rivaroxaban, and
      apixaban into clinical practice has introduced additional management options, but
      also safety concerns when combined with antiplatelet agents. Due to the increased
      risk of bleeding when combining an anticoagulant with 2 antiplatelet agents,
      clinicians should monitor and educate patients on avoiding potential
      complications. The need for continued triple regimens should be periodically
      reviewed.

PMID- 23548646
TI  - Serotonergic and adrenergic drug interactions associated with linezolid: a
      critical review and practical management approach.
AB  - OBJECTIVE: To describe the evidence for serotonergic and adrenergic drug
      interactions with linezolid and discuss clinical management strategies. DATA
      SOURCES: A literature search of PubMed (1947-November 2012), MEDLINE (1946
      November 2012), EMBASE (1974-November 2012), and International Pharmaceutical
      Abstracts (1970-November 2012) was conducted using the terms linezolid, drug
      interaction, serotonin syndrome, serotonin toxicity, sympathomimetic,
      serotonergic agents, and adrenergic agents. Citations of retrieved articles were
      also reviewed. STUDY SELECTION AND DATA EXTRACTION: English-language articles
      describing coadministration of serotonergic or adrenergic agents with linezolid
      to humans were included. Studies published only in abstract form were excluded.
      DATA SYNTHESIS: One prospective study, 6 retrospective studies, and 24 case
      reports were identified describing a serotonergic or adrenergic drug interaction.
      Incidence of serotonin syndrome in patients on linezolid and serotonergic agents
      ranged between 0.24% and 4%. Serotonergic agents determined to have probable
      (according to the Horn Drug Interaction Probability Scale) linezolid interactions
      in case reports included meperidine, citalopram, escitalopram, fluoxetine,
      paroxetine, sertraline, duloxetine, and venlafaxine. Serotonergic agent dose and
      duration of coadministration with linezolid did not appear to influence the
      occurrence of serotonin syndrome. Adrenergic medication coadministration was
      associated with a possible drug interaction as determined by the Horn Drug
      Interaction Probability Scale but did not appear to result in clinically
      significant drug interactions with linezolid. CONCLUSIONS: Linezolid-associated
      serotonergic drug interactions occur more commonly than adrenergic interactions.
      Serotonergic interactions considered probable according to the Horn Drug
      Interaction Probability Scale do not appear to correlate with drug dosage; time
      of onset ranges from <1 to 20 days, and effect resolves in <1 to 5 days after
      discontinuation of offending agents. If coadministration of linezolid and a
      serotonergic agent cannot be avoided, clinicians should be aware of the symptoms
      and management of serotonergic toxicity; close monitoring is recommended and
      additional serotonergic agents should not be used. While adrenergic drug
      interactions with linezolid are less common in clinical practice, monitoring for
      signs of hypertension remains important.

PMID- 23548647
TI  - Current approaches to punitive action for medication errors by boards of
      pharmacy.
AB  - BACKGROUND: To increase disclosure of errors and lead to system improvements,
      publications recommend a nonpunitive approach to medication errors. To our
      knowledge there is no published information regarding the extent or bases on
      which boards of pharmacy invoke punitive action against pharmacists involved in
      medication errors. OBJECTIVE: To determine how often and on what bases boards of
      pharmacy determine punitive action to be taken against pharmacists involved in
      medication error events. METHODS: The policies, procedures, and practices
      regarding medication errors by pharmacists for 49 of the 50 US boards of pharmacy
      were reviewed by pharmacy students at the University of New Mexico as a Safe
      Medication Practices class assignment. RESULTS: Most boards of pharmacy invoke
      punitive action against pharmacists involved in medication errors. Most states do
      not have specific rules or regulations that stipulate errors as actual violations
      and most determinations are made on a case-by-case basis. The major determinants
      of punitive action were error severity, actual patient injury, patient
      complaints, and factors related to the pharmacist. The most common types of
      punitive action include license suspension, probation, or revocation, and fines.
      In at least 17 states, incarceration was also a possible punitive action. The
      most common bases for punitive action were to address public safety/health and
      public complaints. CONCLUSIONS: Despite the fact that punitive action is not
      recommended as best practice for addressing medication errors made by health care
      practitioners, most state boards of pharmacy use punitive measures against
      pharmacists involved in medication errors. Based on current recommendations, such
      actions would not be expected to lead to improvements in the health care system.

PMID- 23548648
TI  - Novel targets in the treatment of advanced melanoma: new first-line treatment
      options.
AB  - OBJECTIVE: To discuss the clinical efficacy and safety of ipilimumab,
      vemurafenib, and investigational agents for the treatment of unresectable stage
      III and stage IV melanoma and define current strategies of first-line treatment
      selection. DATA SOURCES: Literature was accessed through MEDLINE and
      International Pharmaceutical Abstracts (1970-November 2012) using the terms
      melanoma, metastatic melanoma, ipilimumab, vemurafenib, dabrafenib, and
      trametinib. In addition, reference citations from publications identified were
      reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles published in English
      identified from the data sources were evaluated. Studies and abstracts including
      more than 10 adult patients were included in the review. DATA SYNTHESIS:
      Treatment options for unresectable stage III and IV melanoma are poor and have
      remained largely unchanged for the past 40 years. Two randomized Phase 3 clinical
      trials have demonstrated a significant survival benefit with the use of
      ipilimumab compared to a melanoma vaccine (10.1 vs 6.4 months; p = 0.003) and
      compared to dacarbazine (11.2 months, 95% CI 9.4-13.6 vs 9.1 months, 95% CI 7.8
      10.5). Additionally, long-term follow-up has revealed cases of durable responses
      of greater than 3 years. Response rates of 50% and greater have been described in
      vemurafenib-treated patients (1 Phase 1, 1 Phase 2, and 1 Phase 3 randomized
      trial), although duration of response has not been fully determined. Both new
      agents possess unique toxicity profiles including immune-related adverse events
      with ipilimumab and secondary cutaneous cancers reported with vemurafenib use.
      CONCLUSIONS: Treatment strategies have changed for patients with advanced
      melanoma with the use of ipilimumab and vemurafenib as first-line agents.
      Increased clinical experience and further published data with these and
      investigational agents will guide the development of treatment algorithms
      outlining optimal drug selection and sequencing as well as improve management of
      their novel adverse events.

PMID- 23548649
TI  - Systematic review and quality assessment of cost-effectiveness analysis of
      pharmaceutical therapies for advanced colorectal cancer.
AB  - OBJECTIVE: To systematically review and assess the quality of cost-effectiveness
      analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer
      (mCRC). DATA SOURCES: The MEDLINE, EMBASE, Cochrane, and EconLit databases were
      searched for the Medical Subject Headings or text key words quality-adjusted,
      QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December
      31, 2009). STUDY SELECTION: Original CEAs of mCRC pharmacotherapy published in
      English were included. CEAs that measured health effects in units other than
      quality-adjusted life years or LYG and letters to the editor, case reports,
      posters, and editorials were excluded. DATA EXTRACTION: Each article was
      independently assessed by 2 trained reviewers according to a quality checklist
      created by the Panel on Cost-Effectiveness in Health and Medicine. RESULTS:
      Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were
      identified. All studies showed a wide variation in methodologic approaches, which
      resulted in a different range of incremental cost-effectiveness ratios reported
      for each regimen. We found common methodologic flaws in a significant number of
      CEA studies, including lack of clear description for critique of data quality;
      lack of method for adjusting costs for inflation and methods for obtaining expert
      judgment; no results of model validation; wide differences in the types of
      perspective, time horizon, study design, cost categories, and effect outcomes;
      and no quality assessment of data (cost and effectiveness) for the interventions
      evaluation. CONCLUSIONS: This study has shown a wide variation in the methodology
      and quality of cost-effectiveness analysis for mCRC. Improving quality and
      harmonization of CEA for cancer treatment is needed. Further study is suggested
      to assess the quality of CEA methodology outside the mCRC disease state.

PMID- 23548650
TI  - Evidence for therapeutic uses of nebulized lidocaine in the treatment of
      intractable cough and asthma.
AB  - OBJECTIVE: To summarize the efficacy and safety data for use of nebulized
      lidocaine in intractable cough and asthma. DATA SOURCES: A literature search was
      conducted using PubMed (through November 2012), International Pharmaceutical
      Abstracts (1970-December 2012), and Cochrane Library (up to 2012) with the search
      terms nebulization, nebulized or nebulised; administration, inhalation; cough;
      asthma; and lidocaine. Results were limited to human studies published in the
      English language. Referenced citations from relevant publications were also
      reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the
      data sources were reviewed for inclusion. Clinical trials and descriptive studies
      that discussed use of nebulized lidocaine for treatment of intractable cough and
      asthma were included in the review. DATA SYNTHESIS: Seventeen studies were
      identified for review. Seven studies (6 descriptive studies and 1 clinical trial)
      evaluating the use of nebulized lidocaine in intractable cough reported efficacy
      in doses ranging from 10 mg to 400 mg. Five clinical trials in asthma showed
      conflicting results regarding improvement in pulmonary function and
      glucocorticoid-sparing effects. General improvements in pulmonary function as
      well as the initial bronchoconstriction induced by nebulized lidocaine in
      subjects with baseline bronchial hyperreactivity were investigated in 5 studies.
      Overall, the available evidence does not appear to preclude the use of lidocaine
      as a treatment option for intractable cough after failure of traditional cough
      suppressants. Data on its use for short-term glucocorticoid-sparing effects in
      asthma are conflicting. Study limitations, including design, small sample size,
      and inconsistencies in method and adjunctive therapies, should be considered.
      Nebulized lidocaine is well tolerated; however, reports of initial
      bronchoconstriction have occurred. CONCLUSIONS: Although nebulized lidocaine is
      not first-line therapy in intractable cough and asthma, it may provide an
      alternative treatment option in patients who cannot tolerate or are unresponsive
      to other treatments. Appropriate monitoring precautions should be used to ensure
      patient safety.

PMID- 23548651
TI  - Risk of pneumonia in elderly nursing home residents using typical versus atypical
      antipsychotics.
AB  - BACKGROUND: Antipsychotic medications are extensively used in nursing homes for
      management of behavioral and psychiatric disorders in the elderly. Prior research
      suggests that pneumonia is one of the common causes of anti psychotic-related
      mortality in this population. None of the studies compared typical and atypical
      antipsychotics with respect to pneumonia. OBJECTIVE: To examine the risk of
      pneumonia with use of typical versus atypical antipsychotics in dual eligible
      elderly nursing home residents. METHODS: The study involved a retrospective
      cohort design matched on propensity score using Medicare and Medicaid Analytical
      eXtract data from 4 US states. The study population included all elderly dual
      eligible (Medicaid and Medicare) nursing home residents (aged >=65 years) who
      initiated antipsychotics any time between July 1, 2001, and December 31, 2003.
      The risk of pneumonia during the 6-month follow-up period was modeled using a Cox
      proportional model and extended Cox hazard model stratified on matched pairs
      based on propensity score, using atypical agents as the reference category.
      RESULTS: Analysis of Medicaid-Medicare data revealed that there were 49,904 new
      antipsychotic (46,293 atypical and 3611 typical) users in the unmatched cohort
      and 7218 (3609 atypical and 3609 typical) users in the matched cohort. The
      unadjusted rate of pneumonia was 8.17% (4.61 events per person year) for atypical
      users and 5.21% (5.21 events per person year) for typical users. THE RESULTS: HR
      1.17, 95% CI 0.83-1.66; and 50-180 days: HR 1.36, 95% CI 0.87-2.14) suggest that
      there was no significant difference in the risk of pneumonia among typical and
      atypical users. CONCLUSIONS: The study found no differential risk of pneumonia
      between typical versus atypical antipsychotic use in dual eligible nursing home
      residents. Given the differential risk of mortality with typical and atypical
      antipsychotic use in nursing homes, more research is needed to evaluate other
      contributory factors of mortality with respect to these 2 antipsychotic classes.

PMID- 23548652
TI  - Evaluating second-line treatment options for type 2 diabetes: focus on secondary
      effects of GLP-1 agonists and DPP-4 inhibitors.
AB  - OBJECTIVE: To discuss the controversy surrounding selection of second-line type 2
      diabetes mellitus (T2DM) therapy by reviewing available data regarding secondary
      effects of glucagon-like peptide-1 receptor (GLP-1) agonists and dipeptidyl
      peptidase-4 (DPP-4) inhibitors, which include low hypoglycemia risk, weight loss,
      and cardiovascular (CV) and beta-cell function benefits. DATA SOURCES: A MEDLINE
      search (1966-March 2013) was conducted using the following key terms: beta-cell
      protection, blood pressure, DPP-4 inhibitors, exena tide, exenatide extended
      release, GLP-1 agonists, hypoglycemia, lina glip tin, lipid, liraglutide,
      pancreatitis, saxagliptin, sitagliptin, and type 2 diabetes. STUDY SELECTION AND
      DATA EXTRACTION: Identified articles published in English were evaluated for
      inclusion, with priority given to randomized controlled trials in humans
      receiving incretin monotherapy or incretin combination therapy with metformin.
      References identified in these articles were reviewed for additional trials. DATA
      SYNTHESIS: Most patients with T2DM use combination therapy; however,
      determination of the second-line agent that is most appropriate is debatable.
      Prior to the use of incretin therapies, traditional second-line agents included
      sulfonylureas, thiazolidinediones, and basal insulin, all of which demonstrate
      undesirable adverse effects. In addition to improving glycemic control, incretin
      therapies have demonstrated benefits concerning hypoglycemic risk and weight loss
      in addition to potential improvements in CV risk factors and beta-cell function.
      While there are risks associated with using incretins, most patients with T2DM
      are good candidates for incretins and could benefit from their potential
      secondary effects. Cost remains a barrier to initiating these agents.
      CONCLUSIONS: Demonstrated secondary benefits in addition to efficacy may make GLP
      1 agonists and DPP-4 inhibitors a more favorable option than other second-line
      T2DM therapies.

PMID- 23548653
TI  - Effect of the UGT1A1*28 allele on unconjugated hyperbilirubinemia in HIV-positive
      patients receiving Atazanavir: a systematic review.
AB  - OBJECTIVE: To systematically examine the literature assessing the effect of
      uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*28 genetic polymorphisms on
      atazanavir-associated hyperbilirubinemia. DATA SOURCES: MEDLINE (1948-November
      2012), EMBASE (1980-November 2012), International Pharmaceutical Abstracts (1970
      November 2012), Google, and Google Scholar were searched using combinations of
      the following terms: glucuronosyltransferase, glucuronosyltransferase 1A1,
      atazanavir, atazanavir plus ritonavir, or polymorph$. The reference lists of all
      identified articles were manually searched. STUDY SELECTION AND DATA EXTRACTION:
      Studies were included if at least 1 group of patients received atazanavir therapy
      and assessed the effect of UGT1A1*28 variants on bilirubin concentrations or
      atazanavir discontinuation rates. The quality of each study was ranked according
      to the US Preventive Services Task Force 1996 classification system. Information
      extracted included study design, baseline characteristics, treatment regimens,
      UGT1A1*28 genotype frequencies, bilirubin concentrations, incidence of
      hyperbilirubinemia, and atazanavir discontinuation rates. DATA SYNTHESIS: Our
      search produced 12 studies, of which 9 were included (6 full manuscripts [level
      II-2], 2 abstracts, and 1 letter to the editor [level III]). Reported UGT1A1*28
      homozygote genotype frequencies (0.8-23.8%) were in general agreement with the
      literature for the diverse ethnic population captured in the 9 studies. An
      association between the incidence of hyperbilirubinemia and UGT1A1*28 genotype
      (homozygotes > heterozygotes > wild-type) was demonstrated in all studies that
      reported such data (6 of 9 studies). However, the calculated positive predictive
      value for homozygosity and hyperbilirubinemia from pooled data was low (40.3%).
      Only 2 studies (levels II-2 and III) reported rates of atazanavir discontinuation
      due to hyperbilirubinemia and showed some positive correlation with presence of
      the UGT1A1*28 allele. CONCLUSIONS: Based on the available evidence, homozygosity
      of the UGT1A1*28 allele does not strongly predict the incidence of severe
      hyperbilirubinemia. Thus, until large, prospective trials demonstrate otherwise,
      UGT1A1*28 testing does not appear to provide additional information to aid
      clinical decision-making when initiating atazanavir treatment in HIV-infected
      patients.

PMID- 23548654
TI  - Oral terbutaline in replacement for intravenous dopamine in a patient with end
      stage heart failure.
AB  - OBJECTIVE: To describe the replacement of intravenous dopamine with oral
      terbutaline in a patient with American College of Cardiology/American Heart
      Association stage D heart failure (HF). CASE SUMMARY: A 54-year-old male was
      admitted for acute decompensated HF, which was successfully managed by aggressive
      diuresis and intravenous dopamine 3 MUg/kg/min. Multiple attempts to taper
      dopamine to discontinuation led to hypotension and bradycardia. In view of his
      hemodynamic response to dopamine weaning, oral terbutaline 5 mg every 8 hours was
      recommended to replace intravenous dopamine. With the addition of terbutaline,
      the patient continued to be hemodynamically stable, and dopamine was successfully
      discontinued, allowing the patient to be discharged home. DISCUSSION: Radioligand
      binding studies have shown that both beta-1 and beta-2 receptors exist in human
      myocardium. Terbutaline is a beta-2 agonist available in oral dosage form. Small
      single-dose studies have demonstrated that terbutaline improved cardiac output
      and increased heart rate, either directly by its positive inotropic effect or
      indirectly by its pulmonary vasodilatory effect. There are no long-term efficacy
      and safety data on the use of oral terbutaline in the management of HF. However,
      in our case, in which symptomatic improvement and comfort measure were our main
      goals of therapy, the use of oral terbutaline allowed us to successfully
      discontinue dopamine and maintain hemodynamic stability. CONCLUSIONS: The use of
      oral terbutaline to replace intravenous dopamine led to a successful maintenance
      of hemodynamic stability in a patient with advanced stage HF. To our knowledge,
      there have been no previous reports describing the use of oral terbutaline to
      replace intravenous inotropes for maintaining hemodynamic stability.

PMID- 23548658
TI  - Retraction technique for urinary catheterization of women with female genital
      mutilation.
AB  - OBJECTIVE: To evaluate the retraction technique for urinary catheterization of
      women with Type III female genital mutilation (FGM). STUDY DESIGN: The hospital
      records of all women from Sudan, Somalia, Ethiopia, Egypt, Eritrea, and Chad who
      were admitted to King Abdulaziz University Hospital, Jeddah, Saudi Arabia from
      January 1, 2011 to January 1, 2012 were reviewed. Women with Type III FGM who had
      urinary catheterization were identified and their records were examined. RESULTS:
      During the study period, 162 women with Type III FGM had urinary catheterization
      by residents in our hospital. One hundred and twelve (69.1%) women had urinary
      catheterization by the standard procedure and 50 (30.9%) by the retraction
      technique because of failure of the standard procedure. No attempts to use the
      technique were unsuccessful; that is, no procedures were converted to emergency
      defibulation. No complications occurred during insertion or while the catheter
      was in place (37.5+/-5.6h). CONCLUSIONS: The retraction technique provides a safe
      and effective option for urinary catheterization of women with Type III FGM.

PMID- 23548655
TI  - Molecular views of Arf-like small GTPases in cilia and ciliopathies.
AB  - The primary cilia are microtubule-based organelles that protrude from most of the
      eukaryotic cells. Recognized as the cell's antenna, primary cilium functions as a
      signaling hub for many physiologically and developmentally important signaling
      cascades. Ciliary dysfunction causes a wide spectrum of syndromic human genetic
      diseases collectively termed "ciliopathies". Mounting evidences have shown that
      various small GTPases have been implicated in the context of cilia as well as
      human ciliopathies. However, how these small GTPases affect cilia formation and
      function remains poorly understood. Here we review and discuss the ciliary role
      of three Arf-like small GTPases (Arls), Arl3, Arl6, and Arl13b.

PMID- 23548659
TI  - High prevalence of chronic thyroiditis in patients with polycystic ovary
      syndrome.
AB  - OBJECTIVE: A higher prevalence (26.9% versus 8.3% of controls) of autoimmune
      thyroiditis (AIT) in polycystic ovary syndrome (PCOS) has been reported in one
      study to date. We aimed to evaluate the prevalence of clinical, subclinical,
      potential thyroid autoimmune diseases and other organ-specific autoimmunity in a
      group of Italian patients with PCOS. STUDY DESIGN: 113 consecutive patients
      referred to our endocrinology unit as outpatients over 18 months, and diagnosed
      with PCOS according to the Rotterdam criteria, were included in the study, and
      100 age-matched healthy women were enrolled as controls. Each patient was
      evaluated for family and personal history of autoimmune and non-autoimmune
      diseases and tested for autoantibodies against thyroperoxidase, thyroglobulin,
      parietal cells, intrinsic factor, adrenal-cortex, 21-hydroxylase, steroid
      producing cells, 17-alpha-hydroxylase, side-chain cleavage enzyme, islet-cells,
      glutamic-acid decarboxylase, nuclei and mitochondria. All patients had serum TSH,
      FT4 and FT3 tested and patients with thyroid autoantibodies and/or abnormal TSH
      levels had an ultrasound thyroid scan. An oral glucose tolerance test and
      measurements of serum anti-Mullerian hormone (AMH) and inhibin B levels were
      carried out. RESULTS: AIT was present in 30/113 (27%) patients compared with 8%
      of controls (p<0.001). Subclinical hypothyroidism was detected in 13/30 (43%)
      patients with AIT; the remaining patients had normal thyroid function. The
      prevalence of non-thyroid autoantibodies in PCOS patients was not different from
      controls. AMH concentration was higher in PCOS patients compared to controls, but
      there was no difference between AIT and non-AIT groups. CONCLUSIONS: The
      prevalence of AIT in patients with PCOS was significantly higher than in
      controls. No other autoimmune diseases were associated with PCOS. This
      observation suggests that PCOS patients should be screened for AIT.

PMID- 23548660
TI  - Determination of hyperelastic properties for umbilical artery in preeclampsia
      from uniaxial extension tests.
AB  - OBJECTIVE: Preeclampsia often results in altered hemodynamics and structurally
      remodeled umbilical arteries in the fetus--alterations that may be associated
      with arterial stiffening. We therefore hypothesized that the mechanical function
      of preeclamptic (PE) umbilical arteries had increased stiffness compared to
      control. STUDY DESIGN: Umbilical arteries were collected from control (n=9) and
      PE (n=6) pregnancies without any other complications. Samples were tested
      uniaxially in axial and circumferential directions for the passive mechanics. The
      umbilical artery was modeled as a fiber reinforced hyperelastic material in both
      control and PE conditions. RESULTS: The PE arteries were stiffer than control
      arteries at stresses of 20-160 mmHg in the axial direction and 65-200 mmHg in the
      circumferential direction (P<0.05). The PE umbilical arteries exhibited a 58% and
      48% increase in circumferential moduli at the systolic and diastolic blood
      pressure respectively compared to the controls (P<0.05). A hyperelastic model
      showed a substantial increase in both isotropic and anisotropic contribution in
      the mechanical behavior. Collectively, the changes observed correlated to a
      higher collagen fiber density in the PE group with increased hyperelastic
      material parameters (P<0.05). CONCLUSION: PE umbilical arteries demonstrated
      stiffer biomechanics compared to the controls due to the change in collagen fiber
      content. These altered biomechanical and structural changes provide a potential
      snapshot into systemic vasculature remodeling occurring in the newborn.

PMID- 23548661
TI  - Temporal trend in the frequency of ectopic pregnancies in Lombardy, Italy.
AB  - BACKGROUND: In recent years, epidemiological data showed that the incidence of
      ectopic pregnancies (EP) is decreasing, but few data are available on the time
      trend in Southern European populations. METHODS: Using data from the Lombardy
      Region Database, we calculated and standardized the EP rates/10,000 resident
      women and the ratios/1,000 pregnancies. RESULTS: Data regarding 1,777,011
      pregnancies and 17,028 cases of EP were recorded among women resident in Lombardy
      between 1996 and 2010, aged 15-50 years old. The age-adjusted EP rates increased
      from 4.4 in 1996 to 5.8 in 2010. The age-adjusted EP ratio was 9.4/1,000
      pregnancies in 1996 and 9.8 in 2010. Medical treatment increased over the period;
      the proportion of laparoscopic treatment increased from 25.9% in 1996 to 36.3% in
      2010. CONCLUSION: The age-adjusted EP rate and ratio increased between 1996 and
      2010, suggesting that the significance of EP as a public health problem has
      increased in the last years.

PMID- 23548662
TI  - Exploiting individual primary visual cortex geometry to boost steady state visual
      evoked potentials.
AB  - OBJECTIVE: The steady-state visual evoked potential (SSVEP) is an
      electroencephalographic response to flickering stimuli generated partly in
      primary visual area V1. The typical 'cruciform' geometry and retinotopic
      organization of V1 is such that certain neighboring visual regions project to
      neighboring cortical regions of opposite orientation. Here, we explored ways to
      exploit this organization in order to boost scalp SSVEP amplitude via oscillatory
      summation. APPROACH: We manipulated flicker-phase offsets among angular segments
      of a large annular stimulus in three ways, and compared the resultant SSVEP power
      to a conventional condition with no temporal phase offsets. (1) We divided the
      annulus into standard octants for all subjects, and flickered upper horizontal
      octants with opposite temporal phase to the lower horizontal ones, and left
      vertical octants opposite to the right vertical ones; (2) we individually
      adjusted the boundaries between the eight contiguous segments of the standard
      octants condition to coincide with cruciform-consistent, early-latency
      topographical shifts in pattern-pulse multifocal visual-evoked potentials
      (PPMVEP) derived for each of 32 equal-sized segments; (3) we assigned phase
      offsets to stimulus segments following an automatic algorithm based on the
      relative amplitudes of vertically- and horizontally-oriented PPMVEP components.
      MAIN RESULTS: The three flicker-phase manipulations resulted in a significant
      enhancement of normalized SSVEP power of (1) 202%, (2) 383%, and (3) 300%,
      respectively. SIGNIFICANCE: We have thus demonstrated a means to obtain more
      reliable measures of visual evoked activity purely through consideration of
      cortical geometry. This principle stands to impact both basic and clinical
      research using SSVEPs.

PMID- 23548663
TI  - Allergen content and in vivo allergenic activity of house dust mite extracts.

PMID- 23548664
TI  - Usability, human factors and geographic information.

PMID- 23548665
TI  - Factors associated with the risk of adenoma recurrence in distal and proximal
      colon.
AB  - BACKGROUND/AIMS: Colonoscopy may be less effective in preventing cancer in the
      proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit
      differential effect on adenoma recurrence by colon subsite. METHODS: We examined
      the association of age, sex, body mass index, smoking status and use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma
      recurrence among 1,864 participants in the Polyp Prevention Trial. We used
      multinomial logistic regression models to calculate the relative risk ratios
      (RRR) and 95% CI. RESULTS: 733 (39.3%) participants had adenoma recurrence (228
      distal only, 369 proximal only and 136 synchronous proximal and distal adenoma).
      When compared to participants without adenoma recurrence, no factor was
      associated with an increased risk of distal only adenoma recurrence. Age 65-69
      years (RRR = 1.47, 95% CI 1.00-2.16), age >=70 years (RRR = 2.24, 95% CI 1.57
      3.20), and male sex (RRR = 1.73, 95% CI 1.32-2.27) were positively associated
      with proximal only adenoma recurrence. NSAIDs use was associated with a reduced
      risk of adenoma recurrence by similar magnitude in distal (RRR = 0.78, 95% CI
      0.58-1.07) and proximal colon (RRR = 0.77, 95% CI 0.60-1.00). CONCLUSIONS: We did
      not find any modifiable risk factor that differentially increases proximal as
      compared to distal adenoma recurrence to be clinically useful for targeted
      intervention.

PMID- 23548666
TI  - Specific binding of paraprotein to platelet receptors as a cause of platelet
      dysfunction in monoclonal gammopathies.
AB  - The study included 48 untreated patients with monoclonal gammopathies (MG).
      Paraprotein was isolated from the serum of 10 patients with decreased platelet
      aggregation. Platelet aggregation was measured before and after the addition of
      the isolated paraprotein to platelet-rich plasma (PRP) from 10 healthy donors, in
      vitro. Expression of platelet von Willebrand factor (vWF) receptor glycoprotein
      (GP)Ib and platelet collagen receptor GPVI was determined by flow cytometry in
      the PRP of healthy donors before and after the addition of isolated paraprotein
      using the monoclonal antibodies, CD42b (for GPIb) and CD36 (for GPVI).
      Flowcytometry showed that expression of CD42b and CD36 positive cells was reduced
      after the addition of isolated paraprotein to PRP from healthy donors (p <
      0.001). These investigations demonstrated that paraprotein causes platelet
      dysfunction in patients with MG due to specific binding to the platelet vWF
      receptor GPIb and platelet collagen receptor GPVI. 

PMID- 23548667
TI  - Establishment of toxic metal reference range in tobacco from US cigarettes.
AB  - Smoking remains the leading cause of preventable death in the United States.
      There are numerous harmful substances in tobacco and tobacco smoke. Among the
      more than 4,000 identified compounds in smoke, many metals contribute to the
      health risks associated with tobacco use. Specific metals found in tobacco and
      tobacco smoke have been classified as carcinogens by the International Agency for
      Research on Cancer. Exposure to toxic metals can cause outcomes including
      inflammation, sensitization and carcinogenesis. Metals in tobacco are transported
      in tobacco smoke proportionally with their concentrations in tobacco filler for a
      given cigarette design. To quantitatively examine the metal content in numerous
      tobacco products, high throughput methods are desired. This study developed a
      simple, rapid tobacco digestion method coupled with a sensitive analytical method
      using inductively coupled plasma-mass spectrometry. Because of known memory
      effects and volatility of mercury, quantitative determinations of mercury were
      made with a direct combustion analyzer. The methods were utilized to examine
      arsenic, beryllium, cadmium, chromium, cobalt, lead, manganese, mercury and
      nickel contents in cigarette tobacco and to establish a reference range for the
      metals in 50 varieties of cigarettes available in the US. These results are
      comparable to the limited data sets reported by others and with available
      standard reference material values.

PMID- 23548668
TI  - Translocation t(5;18)(q35;q21) as a rare nonrandom abnormality in acute myeloid
      leukemia.
AB  - Cytogenetic abnormalities play an important role in diagnosis, classification and
      prognosis in acute myeloid leukemia (AML). Nevertheless, several chromosome
      abnormalities have not been completely determined, and their prognostic
      significance is currently unknown due to their low incidence and the sporadic
      limited data. We report a case of AML-M2 with a novel, nonrandom translocation
      t(5;18)(q35;q21) in order to clarify the clinical features and outcome of these
      patients which could be advisable for prognostic and therapeutic purposes. This
      translocation has been reported only once in AML. Our patient received intensive
      chemotherapy, but he achieved a complete remission only initially. Eighteen
      months post diagnosis, t(3;12)(p23;p13) was detected as a secondary abnormality
      to t(5;18)(q35;q21) in the progression of the disease. FISH studies confirmed the
      reciprocal t(5;18)(q35;q21) and demonstrated a rearrangement of ETV6 gene as a
      consequence of t(3;12)(p23;p13). The patient died a few days later. In
      conclusion, t(5;18)(q35;q21) is a rare but nonrandom abnormality in AML, found in
      FAB M2 subtype, possibly associated with a rather poor prognosis, while
      t(3;12)(p23;p13) seems to contribute to the progression of the disease. The
      publication of rare, nonrandom chromosome abnormalities such as t(5;18)(q35;q21)
      contribute to the identification of the whole spectrum of cytogenetic
      abnormalities in AML and their prognostic significance.

PMID- 23548669
TI  - Sensilla on antenna and maxillary palp of predaceous fly, Lispe neimongola Tian
      et Ma (Diptera: Muscidae).
AB  - This study describes aspects of sensilla on the antennae and maxillary palps of
      an aquatic predator, Lispe neimongola Tian et Ma. Types, distribution and density
      of sensilla were studied by stereoscopic microscope and scanning electron
      microscopy. The antennal scape has one type of sensilla, the sharp-tipped chaetic
      sensilla; whereas, the antennal pedicel possesses two subtypes of these sensilla.
      Three types of sensilla are found on antennal funiculus: trichoid sensilla,
      basiconic sensilla (two subtypes) and clavate sensilla. Sensilla found on palpal
      surface include the third subtype of basiconic sensilla and chaetic sensilla. Two
      unique sensillar characters of L. neimongola detected are the absence of
      coeloconic sensilla on antennal funiculus and the greater number of basiconic
      sensilla on spoon-like palps. These results are compared with equivalent findings
      in several other Calyptratae fly species of different ecotypes to provide
      evidence of adaptation to their environment.

PMID- 23548670
TI  - The effect of kainic acid on hippocampal dendritic spine motility at the early
      and late stages of brain development.
AB  - Dendrites and spines undergo dynamic changes in physiological conditions, such as
      learning and memory, and in pathological conditions, such as epilepsy.
      Abnormalities in dendritic spines have commonly been observed in brain specimens
      from epilepsy patients and animal models of epilepsy. However, the functional
      implications and clinical consequences of this dendritic pathology for epilepsy
      are uncertain. Motility of dendritic spines and axonal filopodia has been
      recently discovered by the advanced imaging techniques, and remains to a large
      degree an exciting phenomenology in search of function. Here we demonstrate the
      effect of kainic acid (KA), which is a structural analog of glutamate, on
      dendritic spine motility in hippocampal CA1 area at the different stages of brain
      development. In order to reveal the changes that take place in spine and
      filopodial motility in the epileptic model of brain, time-lapse imaging of acute
      hippocampal slices treated with various concentrations of KA after different
      incubation time points was performed. The effects of KA exposure were tested on
      the slices from young (postnatal day (P)7-P10) and adolescent (P28-P30) Thy1-YFPH
      transgenic mice. Slices were treated with either 50 MUM or 100 MUM of KA, for
      either 30 or 100 min. The results obtained in our experiments show diverse
      effects of KA in 2 different age groups. According to our results, 100 MUM/100
      min KA treatment increases spine motility at early stage of brain development
      (P10) by 41.5%, while in P30 mice spine motility is increased only by 3%. Our
      findings also indicate that effect of KA on hippocampal dendritic spine motility
      is predominantly time- rather than concentration-dependent.

PMID- 23548671
TI  - Geographic differences in patterns of genetic differentiation among bitter and
      sweet manioc (Manihot esculenta subsp. esculenta; Euphorbiaceae).
AB  - PREMISE OF THE STUDY: Manioc (Manihot esculenta subsp. esculenta), one of the
      most important tropical food crops, is commonly divided according to cyanide
      content into two use-categories, "sweet" and "bitter." While bitter and sweet
      varieties are genetically differentiated at the local scale, whether this
      differentiation is consistent across continents is yet unknown. * METHODS: Using
      eight microsatellite loci, we genotyped 522 manioc samples (135 bitter and 387
      sweet) from Ecuador, French Guiana, Cameroon, Gabon, Ghana, and Vanuatu. Genetic
      differentiation between use-categories was assessed using double principal
      coordinate analyses (DPCoA) with multivariate analysis of variance (MANOVA) and
      Jost's measure of estimated differentiation (D(est)). Genetic structure was
      analyzed using Bayesian clustering analysis. * KEY RESULTS: Manioc neutral
      genetic diversity was high in all sampled regions. Sweet and bitter manioc
      landraces are differentiated in South America but not in Africa. Correspondingly,
      bitter and sweet manioc samples share a higher proportion of neutral alleles in
      Africa than in South America. We also found seven clones classified by some
      farmers as sweet and by others as bitter. * CONCLUSIONS: Lack of differentiation
      in Africa is most likely due to postintroduction hybridization between bitter and
      sweet manioc. Inconsistent transfer from South America to Africa of
      ethnobotanical knowledge surrounding use-category management may contribute to
      increased hybridization in Africa. Investigating this issue requires more data on
      the variation in cyanogenesis in roots within and among manioc populations and
      how manioc diversity is managed on the farm.

PMID- 23548672
TI  - Expression, purification and refolding of a self-assembling protein nanoparticle
      (SAPN) malaria vaccine.
AB  - There are many ways to present antigens to the immune system. We have used a
      repetitive antigen display technology that relies on the self-assembly of 60
      protein chains into a spherical self-assembling protein nanoparticle (SAPN) to
      develop a vaccine against Plasmodium falciparum malaria. The protein sequence
      contains selected B- and T-cell epitopes of the circumsporozoite protein of P.
      falciparum (PfCSP) and, when assembled into a nanoparticle induces strong, long
      lived and protective immune responses against the PfCSP. Here we describe the
      conditions needed for promoting self-assembly of a P. falciparum vaccine
      nanoparticle, PfCSP-KMY-SAPN, and note pitfalls that may occur when determining
      conditions for other SAPN vaccines. Attention was paid to selecting processes
      that were amenable to scale up and cGMP manufacturing.

PMID- 23548673
TI  - Regulation of MT1-MMP and MMP-2 by the serpin PEDF: a promising new target for
      metastatic cancer.
AB  - The balance of endogenous angiogenic factors in the body is responsible for the
      homeostatic control of angiogenesis during normal physiological circumstances,
      with the disruption of this fragile balance leading to pathologic angiogenic
      events such as those involved in cancer progression. This review focuses
      regulation of the pro-angiogenic factors membrane type-1 matrix metalloproteinase
      (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) by the anti-angiogenic factor
      pigment epithelium-derived factor (PEDF) in the contexts of angiogenesis, cancer
      cell proliferation and metastasis. Understanding the role of PEDF in the
      regulation of MT1-MMP and MMP-2 as it pertains to cancer control is important in
      order to understand whether and how such associations provide a novel target for
      cancer therapy.

PMID- 23548674
TI  - The relationship of NT-proBNP and dialysis parameters with outcome of incident
      haemodialysis patients: results from the membrane permeability outcome study.
AB  - BACKGROUND/AIMS: The association of raised levels of natriuretic peptides with
      elevated risk of mortality was investigated in the present analysis of the
      Membrane Permeability Outcome study. METHODS: N-terminal probrain type
      natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis
      patients, randomised to either high-flux or low-flux. Characteristics of patients
      with NT-proBNP levels below or above the median were descriptively analysed and
      survival analysis was performed. RESULTS: Median NT-proBNP value was 2,124 pg/ml,
      with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival
      probability was lowest in patients with both a history of cardiovascular disease
      and NT-proBNP values above the median (p < 0.001). A multivariate Cox
      proportional hazard model showed interaction between presence of cardiovascular
      diseases and NT-proBNP levels above the median. CONCLUSIONS: NT-proBNP is an
      independent predictor of mortality also in incident haemodialysis patients. Lower
      concentrations associated with high-flux dialysis suggest a possible biological
      link to improved survival in this group.

PMID- 23548675
TI  - Development and validation of a simple and sensitive method for quantification of
      levodopa and carbidopa in rat and monkey plasma using derivatization and UPLC
      MS/MS.
AB  - A simple, selective, and sensitive quantitative method has been developed for the
      simultaneous determination of levodopa and carbidopa in rat and monkey plasma by
      protein precipitation using acetonitrile containing the derivatizing reagent,
      flourescamine. Derivatized products of levodopa and carbidopa were separated on a
      BEH C18 column (2.1 mm * 50 mm; 1.7 MUm particle size) using ultra high
      performance liquid chromatography (UHPLC) without any further purification.
      Tandem mass spectrometry (MS/MS) was used for detection. The method was validated
      over the concentration range of 5-5000 ng/mL and 3-3000 ng/mL for levodopa and
      carbidopa, respectively in rat and monkey plasma. Due to the poor stability of
      the investigated analytes in biological matrices, a mixture of sodium
      metabisulfite and hydrazine dihydrochloride was used as a stabilizer. This method
      was successfully utilized to support pharmacokinetic studies in both species. The
      results from assay validations and incurred samples re-analysis show that the
      method is selective, sensitive and robust. To our knowledge, this is the first
      UHPLC-MS/MS based method that utilizes derivatization with fluorescamine and
      provides adequate sensitivity for both levodopa and carbidopa with 50 MUL of
      sample and a run time of 3.5 min.

PMID- 23548676
TI  - Analysis of tacrolimus and creatinine from a single dried blood spot using liquid
      chromatography tandem mass spectrometry.
AB  - Long term therapeutic drug monitoring and assessment of renal function are
      required in renal transplant recipients on immunosuppressant therapy such as
      tacrolimus. Dry blood spots (DBS) have been used successfully in the clinic for
      many years and offers a convenient, simple and non-invasive method for repeated
      blood tests. We developed and performed a preliminary validation of a method for
      the analysis of tacrolimus and creatinine from a single DBS using liquid
      chromatography-tandem mass spectrometric (LC-MS/MS). Tacrolimus and creatinine
      were extracted from a 6mm punch with a mixture of methanol/acetonitrile
      containing ascomycin and deuterated creatinine as internal standards. A 10 MUl
      aliquot of the extract was analyzed directly after dilution for creatinine with
      normal phase high performance liquid chromatography and multiple reaction
      monitoring. The remainder of the extract was processed and analyzed for
      tacrolimus. The lower limit of quantification for tacrolimus was 1 ng/ml with
      accuracy of 0.34% bias and precision (CV) of 11.1%. The precision ranged from
      1.33% to 7.68% and accuracy from -4.44% to 11.6% bias for the intra- and inter
      day analysis. The lower limit of quantification of creatinine was 0.01 mg/dL with
      precision of 7.94%. Accuracy was based on recovery of additional creatinine
      spiked into whole blood samples and ranged from -2.45% bias at 5 mg/dL to 3.75%
      bias at 0.5 mg/dL. Intra- and inter-day precision was from 3.48 to 4.11%. The
      assay was further validated with DBS prepared from pediatric renal transplant
      recipients. There was excellent correlation between the levels of tacrolimus and
      creatinine obtained from the clinical laboratory and the DBS method developed.
      After additional validation, this assay may have a significant impact on
      compliance with medication intake as well as potentially lowering the cost
      associated with intravenous blood draws in clinical laboratories.

PMID- 23548677
TI  - Innovating innovation rate and its relationship with brains, ecology and general
      intelligence.

PMID- 23548678
TI  - Intravenous paracetamol for patent ductus arteriosus in premature infants - a
      lower dose is also effective. Concerning the article by M.Y. Oncel et al:
      Intravenous paracetamol treatment in the management of patent ductus arteriosus
      in extremely low birth weight infants [Neonatology 2013;103:166-169].

PMID- 23548679
TI  - Seasonal variation in the incidence of aneurysmal subarachnoid hemorrhage
      associated with age and gender: 20-year results from the Yamaguchi cerebral
      aneurysm registry.
AB  - BACKGROUND: This study was a cerebral aneurysm registry study conducted in a
      region with few climatic differences. Based on data collected for over 20 years,
      seasonal variations and characteristics of subarachnoid hemorrhage (SAH) due to
      ruptured aneurysms were analyzed. METHODS: This study included 5,007 patients in
      the Yamaguchi Prefecture with aneurysmal SAH between 1986 and 2005. Incidence
      rates by month, sex, age, severity, and aneurysm site were analyzed. RESULTS: In
      women, seasonal variation was observed, in particular among those aged >=50
      years. Among those aged 50-69 years, the highest incidence was in October, and
      the nadir was in June (peak-to-trough ratio = 1.72). At age >=70 years, this was
      slightly different, with the highest incidence in December and the nadir in July
      (peak-to-trough ratio = 1.48). However, there was no seasonal variation in men
      overall; it was limited to elderly men at age >=70 years, with the highest
      incidence in January and the nadir in July (peak-to-trough ratio = 2.9). Aneurysm
      site and severity showed no relationship with seasonal variation. CONCLUSION: The
      present study shows seasonal variations in the onset of SAH. Seasonal variations
      in SAH differed depending on age and sex.

PMID- 23548680
TI  - Identification, localization and function of a novel neuropeptide, 26RFa, and its
      cognate receptor, GPR103, in the avian hypothalamus.
AB  - Several neuropeptides possessing the RFamide motif at their C-termini (designated
      RFamide peptides) have been characterized in the hypothalamus of a variety of
      vertebrates. Since the discovery of the 26-amino acid RFamide peptide (termed
      26RFa) from the frog brain, 26RFa has been shown to exert orexigenic activity in
      mammals and to be a ligand of the previously identified orphan G protein-coupled
      receptor GPR103. Recently, we have identified 26RFa in the avian brain by
      molecular cloning of the cDNA encoding the 26RFa precursor and mass spectrometry
      analysis of the mature peptide. 26RFa-producing neurons are exclusively located
      in the hypothalamus whereas GPR103 is widely distributed in the avian brain.
      Furthermore, avian 26RFa stimulates feeding behavior in broiler chicks. This
      review summarizes the advances in the identification, localization, and functions
      of 26RFa and its cognate receptor GPR103 in vertebrates and highlights recent
      progress made in birds. 

PMID- 23548681
TI  - Group size of a permanent large group of agile mangabeys (Cercocebus agilis) at
      Bai Hokou, Central African Republic.
AB  - White-eyelid mangabeys (genus Cercocebus) live in groups of highly variable size.
      Because of their semi-terrestrial behaviour and preference for dense forest
      habitats, re-liable data on group size are scarce. During a 5-month study, we
      collected 17 group counts on a habituated group of agile mangabeys (C. agilis) at
      Bai Hokou in the Central African Republic. We found a stable group size of
      approximately 135 individuals. This permanent large grouping pattern is known to
      occur among several populations of white-eyelid mangabeys and is congruent with
      extreme group sizes reported in mandrills at Lope in Gabon.

PMID- 23548682
TI  - Training maltreating parents in elaborative and emotion-rich reminiscing with
      their preschool-aged children.
AB  - OBJECTIVE: In the current study, the effects of training maltreating parents and
      their preschool-aged children in elaborative and emotion-rich reminiscing were
      examined. METHOD: 44 Parent-child dyads were randomly assigned to a training
      (reminiscing) or wait-list (control) condition. All participating parents had
      substantiated maltreatment and were involved with the Department of Child
      Services at the time of enrollment. Children were 3-6 years old (M = 4.88, SD =
      .99) and living in the custody of the participating parent. Dyads in the
      reminiscing condition received four, weekly, in-home sessions in elaborative and
      emotion rich reminiscing. RESULTS: At a follow-up assessment, maltreating parents
      in the reminiscing condition provided more high-elaborative utterances,
      references to children's negative emotions, and explanations of children's
      emotion during reminiscing than did parents in the control condition. Children in
      the reminiscing condition had richer memory recall and made more emotion
      references than did children in the control condition during reminiscing with
      their mothers, but not with an experimenter. CONCLUSION: The findings suggest
      that maltreating parents can be taught elaborative and emotion-rich reminiscing
      skills, with benefits for child cognitive and emotional development. The
      potential clinical utility of a reminiscing-based training for maltreating
      families with young children is discussed.

PMID- 23548683
TI  - Exploring self-perceived growth in a clinical sample of severely traumatized
      youth.
AB  - OBJECTIVE: The aims of this study were threefold: (1) examine the prevalence of
      Posttraumatic Growth (PTG) among severely traumatized youth, (2) systematically
      describe the PTG reported, and (3) study the course of PTG from pre- to post
      treatment. METHOD: The sample consisted of 148 severely traumatized Norwegian
      youth (M age=15, SD=2.2, 79.1% girls) receiving treatment in child mental health
      clinics. The Clinician Administered PTSD Scale for Children (CAPS) was used to
      assess level of posttraumatic stress symptoms (PTSS) pre- and post-treatment. One
      of the questions in CAPS: "How do you think (traumatic event) has affected your
      life?" formed the basis for our analysis of PTG. Words and phrases indicative of
      PTG were identified using the Consensual Qualitative Research method. RESULTS:
      Pre-treatment, the prevalence rate of PTG was low compared to previous findings,
      and reports of PTG were not related to levels of PTSS. The main PTG themes
      identified were: personal growth, relational growth, and changed philosophy of
      life. A sub-theme of personal growth; greater maturity/wisdom, was the most
      salient theme identified both pre- and post-treatment. Age was significantly
      related to reports of PTG; older participants reported more growth. Reports of
      PTG increased significantly from pre- to post-treatment, but were not related to
      decrease in PTSS. CONCLUSIONS: The findings suggest that PTG is not only possible
      for youth, but quite similar to that observed among adults. However, we need to
      carefully consider whether reports of self-perceived positive change among
      traumatized youth actually are indicative of growth, or simply indicative of
      increased vulnerability.

PMID- 23548684
TI  - The Lyme disease debate: host biodiversity and human disease risk.

PMID- 23548685
TI  - Frogs and estivation: transcriptional insights into metabolism and cell survival
      in a natural model of extended muscle disuse.
AB  - Green-striped burrowing frogs (Cyclorana alboguttata) survive in arid
      environments by burrowing underground and entering into a deep, prolonged
      metabolic depression known as estivation. Throughout estivation, C. alboguttata
      is immobilized within a cast-like cocoon of shed skin and ceases feeding and
      moving. Remarkably, these frogs exhibit very little muscle atrophy despite
      extended disuse and fasting. Little is known about the transcriptional regulation
      of estivation or associated mechanisms that may minimize degradative pathways of
      atrophy. To investigate transcriptional pathways associated with metabolic
      depression and maintenance of muscle function in estivating burrowing frogs, we
      assembled a skeletal muscle transcriptome using next-generation short read
      sequencing and compared gene expression patterns between active and 4 mo
      estivating C. alboguttata. This identified a complex suite of gene expression
      changes that occur in muscle during estivation and provides evidence that
      estivation in burrowing frogs involves transcriptional regulation of genes
      associated with cytoskeletal remodeling, avoidance of oxidative stress, energy
      metabolism, the cell stress response, and apoptotic signaling. In particular, the
      expression levels of genes encoding cell cycle and prosurvival proteins, such as
      serine/threonine-protein kinase Chk1, cell division protein kinase 2, survivin,
      and vesicular overexpressed in cancer prosurvival protein 1, were upregulated
      during estivation. These data suggest that estivating C. alboguttata are able to
      regulate the expression of genes in several major cellular pathways critical to
      the survival and viability of cells, thus preserving muscle function while
      avoiding the deleterious consequences often seen in laboratory models of muscle
      disuse.

PMID- 23548686
TI  - Magnetic properties of double exchange biased diluted magnetic
      alloy/ferromagnet/antiferromagnet trilayers.
AB  - The magnetic properties of trilayers consisting of a diluted magnetic alloy, CuMn
      (Cu0.99Mn0.01), a soft ferromagnet, Py(=Ni0.8Fe0.2), and an antiferromagnet,
      alpha-Fe2O3, were investigated. The samples, grown by UHV magnetron sputtering,
      were magnetically characterized in the temperature range T = 3-100 K. Typical
      exchange bias features, namely clear hysteresis cycle shifts and coercivity
      enhancements, were observed. Moreover the presence of an inverse bias, which had
      been already reported for spin glass-based structures, was also obtained in a
      well-defined range of temperatures and CuMn thicknesses.

PMID- 23548687
TI  - Clinical characteristics and time trends in etiology of hepatocellular cancer in
      Germany.
AB  - INTRODUCTION: The incidence of hepatocellular cancer (HCC) continues to rise in
      Europe with a shift of the primary cause towards alcoholic and non-alcoholic
      fatty liver disease. Metabolic factors like diabetes mellitus and overweight have
      been identified as significant risk factors for HCC development. PATIENTS AND
      METHODS: A retrospective analysis in a large single-center cohort of 650 patients
      diagnosed with HCC was performed. Demographic characteristics, risk factors,
      tumor stage at diagnosis and survival were evaluated. RESULTS: Among 650 patients
      (aged 17-87 years, with a male: female ratio of 4:1), 80.8% had underlying liver
      cirrhosis. Alcohol abuse was identified as the only risk factor for liver
      cirrhosis in 52.2% of patients. Viral infection with hepatitis C and hepatitis B
      was present in 13.7 and 3.6% of patients, respectively. 66.1% of patients with
      HCC were overweight with a body mass index exceeding 25, 25.5% even exceeding 30;
      52% of patients had diabetes mellitus. CONCLUSION: Strategies aiming at
      prevention and surveillance of patients at risk to develop HCC in the future need
      to widen the focus from patients with chronic viral hepatitis and a history of
      alcohol abuse to patients with metabolic risk factors.

PMID- 23548688
TI  - In vitro activity of doripenem plus fosfomycin against drug-resistant clinical
      blood isolates.
AB  - The in vitro activity of doripenem in combination with fosfomycin was evaluated
      against a wide range of clinical blood isolates. Bacterial isolates of
      methicillin-resistant Staphylococcus aureus (MRSA; n = 39), Pseudomonas
      aeruginosa (n = 18), multidrug-resistant Escherichia coli (n = 10), Enterobacter
      cloacae (n = 3) and Klebsiella pneumoniae (n = 5) were investigated. For
      synergism testing the checkerboard test was applied and determined by calculation
      of the fractional inhibitory concentration index. Checkerboard results were
      verified by time-kill curve tests on selected isolates. Among MRSA, E. coli and
      K. pneumoniae, 94.9, 80 and 100% of isolates demonstrated synergism,
      respectively. Selected isolates demonstrated synergism in time-kill curve tests.
      P. aeruginosa isolates demonstrated no interaction in all isolates. Doripenem
      plus fosfomycin shows high efficacy with promising results in vitro.

PMID- 23548690
TI  - Taming of the shrew--overcoming extramedullary blast crisis in the era of the new
      tyrosine kinase inhibitors.

PMID- 23548689
TI  - Prenatal expression of MET receptor tyrosine kinase in the fetal mouse dorsal
      raphe nuclei and the visceral motor/sensory brainstem.
AB  - Signaling via MET receptor tyrosine kinase (MET) has been implicated in a number
      of neurodevelopmental events, including cell migration, dendritic and axonal
      development and synaptogenesis. Related to its role in the development of
      forebrain circuitry, we recently identified a functional promoter variant of the
      MET gene that is associated with autism spectrum disorder (ASD). The association
      of the MET promoter variant rs1858830 C allele is significantly enriched in
      families with a child who has ASD and co-occurring gastrointestinal conditions.
      The expression of MET in the forebrain had been mapped in detail in the
      developing mouse and rhesus macaque. However, in mammals, its expression in the
      developing brainstem has not been studied extensively throughout developmental
      stages. Brainstem and autonomic circuitry are implicated in ASD pathophysiology
      and in gastrointestinal dysfunction. To advance our understanding of the
      neurodevelopmental influences of MET signaling in brainstem circuitry
      development, we employed in situ hybridization and immunohistochemistry to map
      the expression of Met and its ligand, Hgf, through prenatal development of the
      mouse midbrain and hindbrain. Our results reveal a highly selective expression
      pattern of Met in the brainstem, including a subpopulation of neurons in cranial
      motor nuclei (nVII, nA and nXII), B6 subgroup of the dorsal raphe, Barrington's
      nucleus, and a small subset of neurons in the nucleus of solitary tract. In
      contrast to Met, neither full-length nor known splice variants of Hgf were
      localized in the prenatal brainstem. RT-PCR revealed Hgf expression in target
      tissues of Met-expressing brainstem neurons, suggesting that MET in these neurons
      may be activated by HGF from peripheral sources. Together, these data suggest
      that MET signaling may influence the development of neurons that are involved in
      central regulation of gastrointestinal function, tongue movement, swallowing,
      speech, stress and mood.

PMID- 23548692
TI  - Calibration of a low-level anti-Compton underground gamma-spectrometer by
      experiment and Monte Carlo.
AB  - In this work we present the experimental and Monte Carlo calibration of the
      Compton-suppressed spectrometer of the IAEA's Environment Laboratories, Monaco.
      For this purpose the GESPECOR code was extended to include the specific geometry
      and to implement the veto logic, integrated with the coincidence summing module
      of the code. The simulation results are in good accordance with experimental
      calibrations. The code is fast and user-friendly, able to evaluate the efficiency
      and the correction factors for nuclides with arbitrary complex decay schemes.

PMID- 23548691
TI  - Viral attachment induces rapid recruitment of an innate immune sensor
      (TRIM5alpha) to the plasma membrane.
AB  - TRIM5alpha (tripartite motif 5alpha) acts as a pattern recognition receptor
      specific for the retrovirus capsid lattice and blocks infection by HIV-1
      immediately after entry. However, the precise mechanisms underlying this rapid
      recognition of viral components remain elusive. Here, we analyzed the influence
      of viral exposure on TRIM5alpha. Total internal reflection fluorescence
      microscopy and lipid flotation assays revealed rapid recruitment of a TRIM5alpha
      subpopulation to the plasma membrane (PM) upon exposure to vesicular stomatitis
      virus-G-pseudotyped HIV-1 viral-like particles (VLPs), but not to envelope (Env)
      less HIV-1 VLPs. TRIM5alpha signals were frequently colocalized with those of HIV
      1 capsid at the PM. Exposure to HIV-1 Env-pseudotyped HIV-1 vectors also
      triggered translocation of endogenous TRIM5alpha to lipid microdomains within
      human T cells. Similarly, clustering of lipid microdomains by a glycosphingolipid
      stereoisomer resulted in rapid TRIM5alpha recruitment to the PM. Of note,
      recruitment of endogenous rhesus TRIM5alpha to the PM prior to HIV-1 infection
      significantly increased the potency of viral restriction. Our data therefore
      suggest the importance of TRIM5alpha recruitment to the PM for TRIM5alpha
      mediated innate immune sensing and restriction of retroviral infection.

PMID- 23548693
TI  - Additional contamination when radon is in excess.
AB  - A study of the behavior of the (222)Rn progeny on clothes, skin and hair has been
      performed in a place with very high radon concentration. In the past, radon
      concentration was established to be about 32 kBq/m(3) in a very high humidity
      environment inside a tourist cave in Extremadura (Spain). The results show that
      (222)Rn daughters are adhered on clothes, skin and hair, adding some radioactive
      concentration to that due to radon and its progeny existing in the breathable
      air.

PMID- 23548694
TI  - Evaluation of sodium activation distribution in the PMMA water phantom after fast
      neutron irradiation.
AB  - (24)Na produced by the neutron activation of stable sodium in the body is
      commonly used to assess neutron doses after criticality accidents. However, the
      (24)Na distribution is not uniform owing to the interaction with the human body.
      In this study, we experimentally evaluated the (24)Na distribution in a PMMA
      water phantom and 60 polyethylene vials. The vials were analyzed to evaluate the
      sodium activation distribution in the PMMA water phantom by employing a
      correction factor. 

PMID- 23548695
TI  - Diet, the human gut microbiota, and IBD.
AB  - The human gut contains a vast number of microorganisms known collectively as the
      "gut microbiota". Despite its importance in maintaining the health of the host,
      growing evidence suggests the gut microbiota may also be an important factor in
      the pathogenesis of various diseases, a number of which have shown a rapid
      increase in incidence over the past few decades. Factors including age, genetics,
      and diet may influence microbiota composition. We used diet inventories and 16S
      rDNA sequencing to characterize fecal samples from 98 individuals. Fecal
      communities clustered into previously described enterotypes distinguished
      primarily by levels of Bacteroides and Prevotella. Enterotypes were associated
      with long-term diets, particularly protein and animal fat (Bacteroides) vs.
      simple carbohydrates (Prevotella). Although the distinction of enterotypes as
      either discrete clusters or a continuum will require additional investigation,
      numerous studies have demonstrated the co-exclusion of the closely related
      Prevotellaceae and Bacteroides genera in the gut microbiota of healthy human
      subjects where Prevotella appears to be a discriminatory taxon for residence in
      more agrarian societies. Ultimately, the impact of diet on the human gut
      microbiota may be an important environmental factor involved in the pathogenesis
      of disease states that show a rapidly increasing incidence in industrialized
      nations such as the inflammatory bowel diseases (IBD).

PMID- 23548696
TI  - Experimental designs for array comparative genomic hybridization technology.
AB  - Array comparative genomic hybridization (aCGH) technology is commonly used to
      estimate genome-wide copy-number variation and to evaluate associations between
      copy number and disease. Although aCGH technology is well developed and there are
      numerous algorithms available for estimating copy number, little attention has
      been paid to the important issue of the statistical experimental design. Herein,
      we review classical statistical experimental designs and discuss their relevance
      to aCGH technology as well as their importance for downstream statistical
      analyses. Furthermore, we provide experimental design guidance for various study
      objectives.

PMID- 23548697
TI  - Effect of new method of intracoronary adenosine injection during primary
      percutaneous coronary intervention on microvascular reperfusion injury - clinical
      outcome and 1-year follow-up.
AB  - OBJECTIVES: The aim of this single-center, randomized placebo-controlled trial in
      70 consecutive patients (64 +/- 14 years) with acute myocardial infarction was to
      examine the role of a new protocol of adenosine administration during primary
      angioplasty on immediate electrocardiographic and angiographic results, clinical
      outcome and 1-year follow-up. METHODS: Group A (n = 35) twice received
      intracoronary adenosine through the guiding catheter: immediately after crossing
      the lesion of the infarct-related artery with guidewire and then after first
      balloon inflation. Group B (n = 35) received placebo. RESULTS: Resolution of ST
      segment elevation was more frequently observed in the adenosine than in the
      placebo group (p < 0.01). Percutaneous coronary intervention (PCI) resulted in
      borderline better TIMI 3 flow after the procedure in the adenosine group than in
      the placebo group. Myocardial blush grade 3 at the end of the procedure was
      significantly improved in the adenosine compared to the placebo group (p < 0.05).
      At 1-year the composite end-point of death, recurrent myocardial infarction,
      heart failure and clinically driven target vessel revascularization was present
      in 8 patients in the adenosine group and 16 patients in placebo group (p < 0.05).
      CONCLUSIONS: Intracoronary adenosine improved electrocardiographic and
      angiographic results in patients undergoing primary PCI and seemed to be
      associated with more favorable clinical course.

PMID- 23548698
TI  - Anterior choroidal artery territory infarction: lesions confined to versus beyond
      the internal capsule.
AB  - BACKGROUND: Studies investigating the clinical features and stroke mechanisms of
      anterior choroidal artery (AchA) infarction have reported inconsistent results.
      This may be partly due to different degrees of inclusion of patients with
      isolated posterior limb of the internal capsule (PLIC) lesions, which may be
      supplied by lenticulostriate arteries rather than AchA. The purpose of this study
      was to investigate clinical features and stroke mechanisms of AchA infarction,
      with particular attention to the above problem. METHODS: We evaluated patients
      with AchA infarction assessed with diffusion-weighted imaging and magnetic
      resonance angiography, who were admitted to the Asan Medical Center from July
      2001 to April 2011. Probable AchA (pAchA) infarction was diagnosed when the
      lesions were confined to the lower part of the PLIC, while definite AchA (dAchA)
      infarction was diagnosed when the lateral geniculate body, the uncus, or the
      cerebral peduncle were concomitantly involved. We assessed imaging findings,
      stroke mechanisms, and clinical features, and investigated the differences
      between patients with dAchA infarction and those with pAchA infarction. RESULTS:
      We identified 127 patients with AchA infarction: 34 with dAchA infarctions, 90
      with pAchA infarctions, and 3 without PLIC lesions. The most important stroke
      mechanism was small artery disease (SAD), followed by large artery disease (LAD).
      In patients with LAD, distal internal carotid artery (ICA) disease was a
      relatively important cause of stroke. The dAchA group, as compared with the pAchA
      group, was more frequently related to cardioembolism (12 vs. 2%, p = 0.03),
      distal ICA steno-occlusion (35 vs. 2%, p = 0.001), severe neurologic deficits
      (higher National Institute of Health Stroke Scale scores and more severe limb
      weakness), and less often associated with SAD (56 vs. 78%, p = 0.02). CONCLUSION:
      In general, SAD was the most important stroke mechanism for AchA infarction
      followed by LAD. However, dAchA infarction and pAchA infarction differ in that
      the former was more often associated with cardioembolism, distal ICA steno
      occlusion, a worse clinical status and less often associated with SAD than the
      latter. The different proportion of patients with pure PLIC lesions included in
      previous studies may have led to inconsistent and confusing results, which should
      be considered to gain a proper understanding of AchA infarction.

PMID- 23548699
TI  - Family functioning in Chinese type 2 diabetic patients with and without
      depressive symptoms: a cross-sectional study.
AB  - BACKGROUND: Patients with depression or type 2 diabetes mellitus (T2DM) often
      have associated impaired family functioning. The purpose of this study was: (1)
      to explore the family functioning of T2DM patients with and without depressive
      symptoms and (2) to explore the relationship between depressive symptoms and
      family impairment in T2DM patients with depressive symptoms. This study used a
      cross-sectional design. SAMPLING AND METHODS: A sample of 32 patients with T2DM
      who had depressive symptoms and 229 patients with T2DM who did not have
      depressive symptoms completed the Chinese versions of the Family Assessment
      Device (FAD) and the Beck Depression Inventory. RESULTS: This study showed that
      there were differences in duration of diabetes and some FAD dimensions between
      T2DM patients with and without depressive symptoms (p < 0.01). There were also
      differences in the frequencies of FAD dimensions between T2DM patients with and
      without depressive symptoms (p < 0.01). Age, duration of diabetes and family
      function were predicting factors of depressive symptoms among T2DM patients (p <
      0.01). CONCLUSIONS: The T2DM patients with depressive symptoms had more unhealthy
      FAD dimensions than the T2DM patients without depressive symptoms. The family
      functioning of T2DM patients with depressive symptoms was worse than that of T2DM
      patients without depressive symptoms. Age, duration of diabetes and some
      dimensions of FAD were associated with depressive symptoms in the T2DM patients.

PMID- 23548700
TI  - Epidemiology of hereditary ataxias in Spain: hospital discharge registry and
      population-based mortality study.
AB  - BACKGROUND: Hereditary ataxias (HA) comprise a group of genetically heterogeneous
      rare diseases. As important public health problems to be monitored, this study
      analyses the morbimortality of HA in Spain. METHODS: Data were extracted from the
      national death index (1981-2008), using the International Classification of
      Diseases (ICD) 9th revision code 334 until 1998, and 10th revision code G11 from
      1999 onwards. ICD-9 codes were then selected from the national discharge dataset
      (1998-2007). Age-adjusted morbidity and mortality rates were obtained by gender
      and 5-year period. RESULTS: Of the 610 HA deaths from 1981 to 2008, 277
      corresponded to Friedreich's ataxia (45.4%) and 333 (54.6%) to other and
      unspecified ataxias (non-Friedreich group). Both groups showed an increase in
      mortality trend, which was more pronounced in males from 1985-1989 to 1990-1994.
      Geographical distribution of mortality revealed higher risk for males, mainly in
      the north of Spain. A total of 5,341 HA hospitalisations were identified from
      1998 to 2007. The average annual age-adjusted hospitalisation rate was 1.19 per
      100,000 population, with a rising trend. CONCLUSION: This increase in morbidity
      and mortality, coupled with the slight interprovincial differences, indicate that
      more attention should be paid to these rare diseases by public authorities and
      society alike.

PMID- 23548701
TI  - Non-natriuretic doses of furosemide: potential use for decreasing the workload of
      the renal outer medulla with minimal magnesium wasting in the rat.
AB  - BACKGROUND/AIMS: Since furosemide (FS) inhibits active Na(+) reabsorption by
      medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease
      its work during periods of low O2 supply to deep in the renal outer medulla. This
      study was designed to demonstrate that there may be a dose of FS would reduce its
      metabolic work while preventing the excessive loss of magnesium (Mg(2+)). Mg(2+)
      is important because the ATP needed to perform work must have bound Mg(2+) to it.
      METHODS: Rats were injected intraperitoneally with a range of doses of FS. The
      measured outcomes were urine flow rate and parameters of functions of the mTAL
      (i.e. urine and renal papillary osmolality and urinary excretion of Na(+), Cl(-),
      K(+) and Mg(2+), and concentrations of Mg(2+) in serum). RESULTS: The urine flow
      rate increased significantly starting at 2.4 mg FS/kg. The renal papillary
      osmolality decreased at >=0.4 mg FS/kg, and the large detectable natriuresis
      started at 1.6 mg FS/kg. At this latter dose, the urinary excretion of Mg(2+)
      rose significantly. CONCLUSION: In rats, the non-natriuretic dose of FS may
      reduce the work of the mTAL. The earliest indicator of reduced work in the mTAL
      appears to be a decrease in urine osmolality rather than a rise in urine flow
      rate. Higher doses of FS should be avoided, as they induce high rates of Mg(2+)
      excretion, which can deplete the body of this essential electrolyte.

PMID- 23548702
TI  - The putative JAK-STAT inhibitor AG490 exacerbates LPS-fever, reduces sickness
      behavior, and alters the expression of pro- and anti-inflammatory genes in the
      rat brain.
AB  - The functional significance for activation of inflammatory transcription factors,
      such as signal transducer and activator of transcription (STAT3), nuclear factor
      (NF)kappaB or NF-interleukin (IL)6 and their contribution to the induction of
      brain controlled sickness responses, such as fever, during infection and
      inflammation is unknown. Using AG490, previously shown to inhibit the STAT3- and
      NF-IL6-signaling pathway, we therefore investigated the central involvement of
      these two signaling pathways in mediating sickness behavior, fever and
      accompanying brain inflammation induced by peripheral lipopolysaccharide (LPS)
      stimulation. Rats pre-treated i.c.v. with AG490 1 h before the i.p. LPS-challenge
      (100 MUg/kg) showed a modestly exaggerated fever, attenuated adipsia and almost
      unimpaired locomotor activity compared to LPS-controls receiving vehicle
      (i.c.v.). The LPS-induced anorexia was not altered and AG490 did not have any
      effect on rats receiving PBS (i.p.). We did observe effects of AG490 on STAT3
      signaling at 4 h, while AG490-mediated changes in brain activity of inflammatory
      transcription factors at 8 h were not significant. Increased NF-IL6 and
      suppressor of cytokines 3 mRNA-expression in AG490/LPS-treated rats were
      indicative of a compensative activation at 24 h. Moreover, a significant decrease
      in hypothalamic anti-inflammatory IL-10-expression and an increase in
      inflammatory microsomal prostaglandin E synthase (mPGES) mRNA-expression 8 h
      after LPS-injection was revealed in AG490 pre-treated animals compared to solvent
      treated LPS-controls. In summary, we have shown a dissociation between the
      effects of central AG490 treatment on fever and components of sickness behavior,
      which appears to be related to reduced IL-10 and increased mPGES-expression in
      the brain. Thus, AG490 might have therapeutic potential to reduce sickness
      behavior.

PMID- 23548703
TI  - The effect of forest fragment characteristics on abundance of Colobus vellerosus
      in the forest-savanna transition zone of Ghana.
AB  - We explore the factors influencing the abundance of Colobus vellerosus in 11
      forest fragments [Boabeng-Fiema Monkey Sanctuary and 9 surrounding forest
      fragments (range: 3.2-190 ha)] in the forest-savanna transition zone of Ghana. We
      used a 'complete' count for the colobus census in the fragments. We determined
      the fragment sizes using geographic information system methods and assessed
      forest fragment quality (tree species richness). Colobus individuals were absent
      from 4 forest fragments but present in 7 (densities of 0.13/ha-1.63/ha). We
      modelled colobus density using Poisson regression and selected models based on
      corrected Akaike information criterion model weights. Fragment size and tree
      species richness in the fragments were positively associated with colobus
      density, whereas isolation distance of the forest fragments (range: 20-5,632 m)
      was negatively associated with colobus density. Our analysis suggests that the
      isolation distance between the fragments and Boabeng does impede colobus
      movement. As the colobus populations in Boabeng and Fiema increase, some of the
      unoccupied fragments may become more attractive to dispersing monkeys. Management
      measures that aim at increasing tree species richness within fragments, while
      maintaining some large trees between fragments, might help to increase the
      occupancy of some of the fragments that currently have no permanent colobus
      groups.

PMID- 23548704
TI  - Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer
      agents: design, synthesis and biological screening.
AB  - Nuclear factor-kappaB (NF-kappaB) has been reported to regulate various genes
      involved in cancer and inflammation. Accordingly, drugs suppressing or inhibiting
      NF-kappaB may possess both anti-inflammatory and anticancer properties. A library
      of quinolone substituted thiazolidin-4-ones was docked into the active site of NF
      kappaB and the top-ranked 31 compounds were synthesized and evaluated for anti
      inflammatory and anticancer activity. The best-ranked compound 6b showed highest
      anti-inflammatory activity in carrageenan-induced paw edema model. In vitro
      anticancer studies revealed 1a and 16a as most active compounds against BT-549,
      HeLa, COLO-205 and ACHN human cancer cell lines. Compounds 1a and 16a exhibited
      NF-kappaB dependent anticancer properties and apoptosis mediated cell death. In
      vivo Ehrlich ascites carcinoma study further confirmed the antitumor activity of
      1a and 16a.

PMID- 23548705
TI  - An undiagnosed left sided traumatic diaphragmatic hernia presenting as small
      intestinal strangulation: A case report.
AB  - INTRODUCTION: Post traumatic diaphragmatic hernia is very often missed
      particularly in polytrauma patients. We present case of an isolated post
      traumatic diaphragmatic hernia with strangulation, a very rare finding.
      PRESENTATION OF CASE: A 35 year old man presented with features of intestinal
      obstruction with past history of a seemingly trivial blunt thoracic injury 15
      years back. Findings of X-ray abdomen and chest with high leukocyte count raised
      suspicion of obstructed diaphragmatic hernia which on exploration revealed
      obstructed diaphragmatic hernia with gangrenous bowel segment. DISCUSSION: Blunt
      injury of diaphragm is relatively common and is considered as a marker of severe
      trauma and it can clinically be occult as other violent injuries may mask and
      disguise its initial clinical presentation(1) resulting in late presentation with
      obstruction and/or rarely strangulation. An early diagnosis of the condition is
      prudent to avoid morbidity and mortality associated with late presentations.
      CONCLUSION: In a patient of intestinal obstruction with history of even trivial
      throraco- abdominal injury, diagnosis of diaphragmatic hernia should be kept in
      mind.

PMID- 23548706
TI  - Concomitant jejunal sarcomatoid carcinoma and gastric GIST in patient with
      polymyalgia rheumatica: A case report.
AB  - INTRODUCTION: Sarcomatoid carcinoma (SCA) of the small bowel is an extremely rare
      tumor with only 21 cases reported in literature and GISTs are relatively rare
      gastrointestinal neoplasms. PRESENTATION OF CASE: We report a case of an 85 year
      old female admitted with intestinal obstruction in June 2010. She suffered from
      polymyalgia rheumatica and was under surveillance for a presumed gastric GIST. A
      laparotomy was performed with resection of the jejunal obstruction and complete
      excision of the gastric mass. Histology confirmed a gastric GIST and sarcomatoid
      carcinoma of the small bowel. The patient was discharged 21 days after the
      operation and died on the 88th post-operative day. DISCUSSION: Synchronous GISTs
      and other malignancies have been reported over the last years with increasing
      frequency. Sarcomatoid carcinoma of the small bowel is an aggressive neoplasm
      with poor survival rates and surgery is the cornerstones of treatment. Given its
      unpredictable clinical behaviour and concomitant association with other
      malignancies, GISTs require adequate surgical resection with careful, long-term
      follow-up. CONCLUSION: This is the first case of concomitant gastric GIST with
      Sarcomatoid carcinoma of the small bowel, and the first report of sarcomatoid
      small bowel carcinoma in association with polymyalgia rheumatica.

PMID- 23548707
TI  - "Emergency" definitive reconstruction of a necrotising fasciitis thigh
      debridement defect with a pedicled TRAM flap.
AB  - INTRODUCTION: Necrotising fasciitis (NF) is a rare, severe, rapidly progressing
      and life-threatening synergistic infection primarily affecting the superficial
      fascia. A novel method of definitive and aesthetic reconstruction of NF thigh
      defects by using a pedicled transverse rectus abdominis myocutaneous (TRAM) flap
      without recourse to temporising skin grafts is presented. PRESENTATION OF CASE: A
      30-year-old parous woman presented in extremis with fulminant NF of her left
      anteromedial thigh. Following emergency radical debridement and intensive care
      stabilisation she was reconstructed 48h later in a single stage with a pedicled
      TRAM flap islanded on the ipsilateral deep inferior epigastric vessels. There was
      excellent contour restoration of her thigh and coverage of the exposed femoral
      vessels. DISCUSSION: Pedicled flaps based on the rectus abdominis muscle provide
      a large, readily available reconstructive option for correction of substantial
      regional defects as herein illustrated. They are robust when based on dominant
      inferior vascular pedicle with a long reach and wide arc of rotation when
      designed transversely (as a TRAM flap). CONCLUSION: This case also illustrates
      that definitive flap reconstruction of NF can be successfully undertaken in the
      emergent setting, thereby negating the need for large areas of skin grafting
      which can lead to contractures with consequent functional impairment and
      suboptimal aesthetic results.

PMID- 23548708
TI  - Secret ingredients: who knows what's in your food?

PMID- 23548709
TI  - Experimental and theoretical study of CePdBi.
AB  - In this paper we present experimental results obtained for CePdBi by means of
      specific heat, electrical resistivity, magnetization and x-ray photoemission
      spectroscopy (XPS) measurements as well as fully relativistic band structure
      calculations. CePdBi crystallizes in MgAgAs structure and exhibits a transition
      to a magnetically ordered state at TM ~/= 2 K, and a subsequent transition to a
      superconducting state at TC ~/= 1.3 K. The superconducting phase has a
      significant critical field of about 1.4 T. The x-ray diffraction, resistivity and
      magnetic susceptibility data show that CePdBi exhibits significant atomic
      disorder, which is a typical feature of Heusler alloys. It seems that the
      superconducting transition is caused by part of the disordered phase, which from
      the Meissner shielding can be estimated to constitute ~8% of the sample volume.
      Due to atomic disorder, CePdBi exhibits metamagnetic behavior below TM and spin
      glass-like features just above TM. Band structure calculations confirm the
      magnetic ground state of the CePdBi system and the possibility of formation of a
      narrow pseudogap near the Fermi level, which can also be seen in resistivity
      data. The spin-orbit interaction strongly influences the band structure and the
      shape of the semiconducting gap.

PMID- 23548710
TI  - Genomics research: the underpinning of infectious disease prevention and control
      strategies.

PMID- 23548711
TI  - Genetic susceptibility to West Nile virus and dengue.
AB  - This article focuses on the host genetic predisposition to 2 viruses, West Nile
      virus and dengue virus, which belong to the genus Flavivirus. Although by
      definition these viruses have shared characteristics (e.g. similar size, single
      stranded, RNA viruses, both transmitted by the bite from an infected mosquito),
      they differ greatly in epidemiology and clinical manifestations. The text below
      not only summarizes the genetic factors that predispose to complications of these
      2 important flaviviruses, but also illustrates the challenges in determining the
      genomic basis for complications to these viruses.

PMID- 23548712
TI  - The role of polymorphisms in host immune genes in determining the severity of
      respiratory illness caused by pandemic H1N1 influenza.
AB  - Following the influenza epidemics, it has become clear that severity of illness
      is not uniform. Comorbidities and immunocompromise account for only a fraction of
      severe cases and do not explain the differential severity among the otherwise
      healthy during pandemics. During the 2009 H1N1 pandemic, a focus has been placed
      on better understanding of the determinants and pathogenesis of severe influenza
      infections. Much of the current literature has focused on viral genetics and its
      impact on host immunity as well as novel risk factors for severe infection
      (particularly within the H1N1 pandemic). The improved understanding of the
      cellular mechanisms and pathways involved in the pathogenesis of severe disease
      along with technological advances have allowed a more systematic approach to the
      exploration of the host genetic determinants of susceptibility and severe
      respiratory illness. By better defining the role of genetic variability in the
      immune responses to influenza, and identifying key polymorphisms that either
      protect against severe manifestation or those that impair the host immune
      response, it is possible to envision better methods to identify at-risk
      populations and new targets for therapeutic interventions and vaccines. This
      review will summarize the accumulated literature examining the immunogenetic
      factors associated with propensity for the development of severe pandemic H1N1
      (pH1N1) manifestations. We will focus on novel and key insights gained through
      study of ethnic populations that appeared more vulnerable to severe disease
      during the 2009 H1N1 pandemic.

PMID- 23548713
TI  - The genetics of susceptibility to variant Creutzfeldt-Jakob disease.
AB  - The emergence of bovine spongiform encephalopathy (BSE) in cattle and,
      subsequently, its transmission to humans resulting in variant Creutzfeldt-Jakob
      disease (vCJD) in the UK has proved to be one of the major public health scares
      of the century. The oral route of infection, the long incubation period, and the
      incredible resistance of the transmissible infectious agent to various forms of
      decontamination poses unique challenges. Fortunately, despite extensive exposure
      of the UK population to contaminated meat, the size of the vCJD epidemic that has
      emerged since its initial detection is relatively low (225 worldwide). An
      explanation for this disparity is as yet incomplete, but the development of the
      disease is likely influenced by a number of factors including physical properties
      of the infectious agent, environmental factors such as the route and amount of
      exposure and individual susceptibility factors. This review focuses on current
      knowledge of the genetic factors that undoubtedly play a major role in
      influencing the development of vCJD. In terms of genetic susceptibility, the best
      characterised is the common single nucleotide polymorphism at codon 129 of the
      human prion protein gene (PRNP). Moreover, several other polymorphisms and
      mutations have been identified that may affect susceptibility as well as other
      important disease characteristics such as the highly variable prion disease
      incubation period.

PMID- 23548714
TI  - Public health genomics and the new molecular epidemiology of bacterial pathogens.
AB  - Laboratory methods that can unambiguously fingerprint pathogenic microbes are
      needed to investigate the transmission of human infectious diseases from diverse
      sources, such as from the community, from the environment, within hospitals, or
      from contaminated food or water sources. Public health investigations currently
      rely on laboratory subtyping methods that ultimately provide only a fraction of
      the total genetic information of a pathogen, and although there is widespread
      success using existing subtyping methods, they do not always provide sufficient
      evidence to link disease cases together into outbreaks or to link these human
      cases to the culprit source. Alternatively, whole-genome sequencing of bacterial
      pathogens provides an unabridged examination of the genetic content of individual
      pathogen isolates, enabling public health laboratories to benefit from
      comparative analyses of total genetic content. In this context, whole-genome
      sequencing represents the ultimate epidemiological typing method - a universally
      applicable, highly detailed typing platform capable of providing the entire
      genetic blueprint of a pathogen and distinguishing strains to the single
      nucleotide level. These new genomic methods, if implemented within existing
      public health laboratory response programs, promise to revolutionize the ability
      of the laboratory to provide information and evidence on the evolution,
      transmission and virulence for bacterial pathogens - and this revolution is
      launching the new field of 'genomicepidemiology'.

PMID- 23548715
TI  - Recent advances in research of HIV infection: implications of viral and host
      genetics on treatment and prevention.
AB  - The genetic diversity among human immunodeficiency virus (HIV) subtypes as well
      as the variability of viral sequences found in HIV-infected individuals presents
      a number of difficult obstacles for the development of universally effective HIV
      treatment and prevention methods. Here, we present a brief summary of recent
      developments in the analysis of viral genetics and human genomics to provide
      insight into future methods for HIV treatment and prevention. Recent studies have
      mined viral sequences found in newly infected individuals to identify common
      features of all transmitted viruses that could provide potential targets for HIV
      vaccine development. Analysis of human immunogenetics has identified specific
      alleles associated with reduced virus loads in HIV-infected individuals providing
      valuable information that may influence individual responses to treatment and
      prevention methods. Increased sensitivity of antiretroviral drug resistance
      testing has improved the detection of hidden drug resistant virus but also
      highlighted the potential for drug resistant viruses to reduce the effectiveness
      of clinical treatment regimens. The rapidly expanding amount of data generated by
      studies of viral genetics and human immunogenetics will provide valuable
      information to guide the design of new strategies to improve clinical treatment
      and enhance HIV vaccine development.

PMID- 23548716
TI  - Malaria diagnostics and surveillance in the post-genomic era.
AB  - Genome sequences are available for 3 human-infecting malaria parasites,
      Plasmodium falciparum, P. vivax and P. knowlesi, and population genomics data are
      available for many endemic regions. This review summarizes how genomic data have
      been used to develop new, species-specific molecular targets for better malaria
      diagnosis. The combination of bioinformatics and genomics has been used to
      identify new sequence targets suitable for diagnostic applications and assess
      their viability within the context of global Plasmodium sequence variation. The
      selection criteria maximized the sensitivity and specificity of the novel
      targets. At least one target from each species was found to be suitable for
      molecular diagnosis of malaria with some advantages over existing molecular
      methods. The promise of using genome sequence data to develop sensitive, genus-
      or species-specific diagnostic methods for other pathogens of public health
      interest is strong. This undertaking together with what we envision as the future
      of malaria diagnosis in the 'omic' era is discussed.

PMID- 23548717
TI  - Host genomics and control of tuberculosis infection.
AB  - Tuberculosis (TB), caused by the human pathogenic bacterium Mycobacterium
      tuberculosis, poses a major global health problem. The tubercle bacillus is
      transmitted from person to person by aerosol, but only a proportion of those in
      contact with infectious aerosol particles will become infected. If infection
      occurs, less than 10% of those infected will develop clinical signs of TB, while
      the majority will develop latent TB infection (LTBI). The identification and
      treatment of LTBI persons is a major aspect of TB control, especially in low
      incidence, highly developed nations. In the absence of a gold standard test for
      latent TB, infection is inferred with the help of either the in vivo tuberculin
      skin test or in vitro interferon gamma release assays of anti-mycobacterial
      immunity. Recent work has observed high heritability of these immune assays
      indicating the critical role of the host genetic background on the establishment
      of infection and latency. Additional genetic studies have identified the host
      genetic background as an important covariate for the proper interpretation of the
      results obtained from LTBI assays. Taken together, these data suggest TB
      surveillance and control can likely be improved by including host genetic
      information into the interpretation of these widely used assays.

PMID- 23548718
TI  - Chlamydia trachomatis infections and subfertility: opportunities to translate
      host pathogen genomic data into public health.
AB  - Chlamydia trachomatis (CT) infections in women can result in tubal pathology
      (TP). Worldwide 10-15% of all couples are subfertile, meaning they did not get
      pregnant after 1 year. Part of the routine subfertility diagnostics is the
      Chlamydia Antibody Test (CAT) to decide for laparoscopy or not in order to
      diagnose TP. The CAT positive and negative predictive value is such that many
      unneeded laparoscopies are done and many TP cases are missed. Addition of host
      genetic markers related to infection susceptibility and severity could
      potentially improve the clinical management of couples who suffer from
      subfertility. In the present study, the potential translational and clinical
      value of adding diagnostic host genetic marker profiles on the basis of infection
      and inflammation to the current clinical management of subfertility was
      investigated. This review provides an overview of the current state of the art of
      host genetic markers in relation to CT infection, proposes a new clinical
      diagnostic approach, and investigates how the Learning-Adapting-Leveling model
      (LAL, a public health genomic (PHG) model) can be of value and provide insight to
      see whether these host genetic markers can be translated into public health. This
      review shows that the preliminary basis of adding host genetic marker profiles to
      the current diagnostic procedures of subfertility is present but has to be
      further developed before implementation into health care can be achieved. CT
      infection is an example in the field of PHG with potential diagnostic to be taken
      up in the future in the field of subfertility diagnosis with a time line for
      integration to be dependent on enhanced participation of many stakeholders in the
      field of PHG which could be advanced through the LAL model.

PMID- 23548719
TI  - Deep sequencing in pre- and clinical vaccine research.
AB  - Vaccine research has experienced a quantum leap after the beginning of the
      genomics era. High-throughput sequencing techniques, unlimited computing
      resources, as well as new bioinformatic algorithms are now changing the way we
      perform genomic studies. Whole genome sequencing will soon become the gold
      standard for phylogenetic and epidemiology studies and is already shedding new
      light on the dynamics of bacterial evolution. We believe that deep sequencing
      projects, together with structural studies on vaccine candidates, will allow
      targeting constant epitopes and avoid vaccine failure due to antigenic
      variability. Systems biology, which is expected to revolutionize vaccine research
      and clinical studies, greatly relies on high-throughput technologies such as RNA
      seq. Furthermore, genomics is a key element to develop safer vaccines, and the
      accuracy of deep sequencing will allow monitoring vaccine coverage after their
      introduction on the market.

PMID- 23548720
TI  - Genomics for public health improvement: relevant international ethical and policy
      issues around genome-wide association studies and biobanks.
AB  - Genome-wide association studies and biobanks are at the forefront of genomics
      research and possess unprecedented potential to improve public health. However,
      for public health genomics to ultimately fulfill its potential, technological and
      scientific advances alone are insufficient. Scientists, ethicists, policy makers,
      and regulators must work closely together with research participants and
      communities in order to craft an equitable and just ethical framework, and a
      sustainable environment for effective policies. Such a framework should be a
      'hybrid' form which balances equity and solidarity with entrepreneurship and
      scientific advances. A good balance between research and policy on one hand, and
      privacy, protection and trust on the other is the key for public health
      improvement based on advances in genomics science.

PMID- 23548721
TI  - Dasatinib maintenance therapy after allogeneic hematopoietic stem cell
      transplantation for an isolated central nervous system blast crisis in chronic
      myelogenous leukemia.
AB  - A 22-year-old male with Ph-positive chronic myelogenous leukemia (CML) was
      started on treatment with imatinib. After 12 months of therapy, he achieved a
      complete cytogenetic response (CCyR). Although the CCyR persisted in his bone
      marrow, he developed an isolated CML blast crisis in his central nervous system
      (CNS) after 29 months of therapy. He underwent allogeneic hematopoietic stem cell
      transplantation (HSCT) following combination therapy with dasatinib, intrathecal
      chemotherapy and cranial irradiation. Subsequently, 168 days after allogeneic
      HSCT, he was started on dasatinib maintenance therapy to prevent a CNS relapse.
      Thirty-eight months after allogeneic HSCT, he has sustained a complete molecular
      response in both bone marrow and CNS. We believe dasatinib has the potential to
      prevent CNS relapse if used for maintenance therapy after allogeneic HSCT. 

PMID- 23548722
TI  - Bitter taste perception and dietary intake patterns in irish children.
AB  - BACKGROUND/AIMS: Variations in bitter receptor gene TAS2R38 affect the perception
      of bitter-tasting compound 6-n-propylthiouracil (PROP). The perception of PROP
      has been associated, in some reports, with the perception of fat and sweet
      tastes, and various food preferences and intakes. The aim was to investigate
      nutrient intakes and food patterns in a group of Irish children, using K-means
      cluster analysis, and compare these with TAS2R38 genotype and PROP taster status.
      METHODS: Dietary intake was measured via a 3-day diet history in 483 children
      aged 7-13 years. Children were genotyped for TAS2R38 variation, and PROP taster
      status was assessed. Anthropometric and socioeconomic data were also obtained.
      RESULTS: No differences were observed in macronutrient, micronutrient, or food
      group consumption between the TAS2R38 genotype and PROP taster groups. K-means
      cluster analysis identified two distinct dietary patterns, termed 'more
      healthful' and 'less healthful' clusters. The clusters did not differ in
      frequencies of TAS2R38 genotype nor PROP taster status groups, suggesting that
      dietary patterns are not influenced by bitter taste perception. CONCLUSION:
      Bitterness perception, as measured by either TAS2R38 genotype or PROP taster
      status, does not appear to exert a significant effect on patterns of dietary
      intakes.

PMID- 23548723
TI  - Long-term intraocular pressure changes in patients with neovascular age-related
      macular degeneration treated with ranibizumab.
AB  - BACKGROUND/AIMS: To investigate the long-term effects of multiple intravitreal
      injections (IVTs) of ranibizumab (Lucentis) on intraocular pressure (IOP) in
      patients with neovascular age-related macular degeneration. METHODS: In 320 eyes,
      IOP measurements were performed at baseline prior to injection and compared with
      IOP measurements of the last visit. Correlations between mean IOP change and
      total number of IVTs, visual acuity or patient age were tested. RESULTS: The mean
      IOP increase was 0.8 +/- 3.1 mm Hg (p < 0.0001). Seven eyes showed final IOP
      values between 22 and 25 mm Hg. The mean follow-up was 22.7 +/- 14.1 months. No
      further correlations between IOP change and number of IVTs, visual acuity or
      patient age have been found. CONCLUSIONS: This study demonstrated a statistically
      significant IOP increase in patients treated with repeated injections of
      ranibizumab. However, IOP increase required no glaucoma treatment during the
      study. Therefore, repeated injections with ranibizumab can be considered safe
      with regard to long-term IOP changes in patients without ocular hypertension or
      glaucoma.

PMID- 23548724
TI  - Description of free-flowing pleural effusions in medical reports after
      echographic assessment.

PMID- 23548726
TI  - Endovascular treatment of very small and very large ruptured aneurysms of the
      anterior cerebral circulation: a single-center experience.
AB  - INTRODUCTION: Endovascular treatment of aneurysms has been introduced as a less
      invasive method for decreasing the rate of aneurysm rerupture and subsequent
      subarachnoid hemorrhage. The outcome and complication rate for endovascular
      treatment of very small (<=3 mm) and very large (15-25 mm) intracranial aneurysms
      has been controversial. Here we report our experience with endovascular coiling
      of very small and very large ruptured aneurysms of the anterior cerebral
      circulation. METHODS: Patients were included in the study if the maximum
      dimension of the intracranial ruptured aneurysm was reported to be <=3 mm or 15
      25 mm and if the aneurysm was within the anterior cerebral circulation. The
      largest dimension was calculated using CT angiography and was confirmed by
      digital subtraction angiography. Endovascular coiling was performed using
      Guglielmi detachable coils. All patients underwent follow-up contrast MR
      angiography every 6 months. RESULTS: A total of 40 cases (18 females and 22
      males) were included in this single-center study. Twenty-one very small and 19
      very large ruptured aneurysms were analyzed. Preprocedural Hunt and Hess grades
      were determined. Endovascular coiling was performed successfully in most cases
      (97.5%), with unsuccessful coiling in 1 patient with a very small ruptured
      aneurysm. In the very small aneurysm group, the most common location was the
      anterior communicating artery and, in the large aneurysm group, the most common
      location was the middle cerebral artery (MCA) bifurcation. The mean follow-up
      time was 15.08 months (range: 6-30 months). The 6th month modified Rankin scale
      (mRS) values for very small aneurysm cases were 0 (no symptoms at all) in 16
      cases (76.2%) and 1 (no significant disability despite symptoms) in 5 cases
      (23.80%). For the very large aneurysm cases, the mRS values were 1 in 2 cases
      (10.5%), 2 in 7 cases (36.8%), 3 in 6 cases (31.6%), 4 in 3 cases (15.8%) and 6
      in 1 case (died due to vasospasm 72 h later; 5.2%). The immediate complications
      that were observed were MCA branch occlusion in 1 very small aneurysm patient and
      early vasospasms in 3 very large aneurysm patients. The late complication that
      was observed was recanalization in 1 very small aneurysm case (1/21, 4.76%) and
      in 5 very large aneurysm cases (5/18, 27.77%). CONCLUSION: Endovascular treatment
      of very small aneurysms is an effective method of treatment with acceptable
      immediate and long-term outcomes. Immediate and long-term complications were more
      prevalent in very large ruptured aneurysms.

PMID- 23548727
TI  - Leucine-rich glioma inactivated 3 associates negatively with adiponectin.
AB  - Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of
      LGI/epitempin family. We previously reported that LGI3 was expressed in adipose
      tissues and suppressed adipogenesis through its receptor, ADAM23. We proposed
      that LGI3 may be a candidate adipokine with pro-inflammatory activity. To
      investigate the role of LGI3 in adipose tissues, we analyzed cytokine profile in
      LGI3 knockout mice. Protein array analysis showed that adiponectin was
      significantly increased in adipose tissues and plasma of LGI3 knockout mice.
      SiRNA-mediated knockdown of LGI3 increased adiponectin in 3T3-L1 preadipocytes.
      Treatment of differentiating 3T3-L1 cells with LGI3 protein decreased adiponectin
      in a dose-dependent manner. High fat diet (HFD)-fed mice showed expression of
      LGI3 in adipose tissue macrophages in addition to adipocytes that expressed LGI3
      in both normal chow-fed and HFD-fed mice. The 60-kDa LGI3 was selectively
      increased in adipose tissues of HFD mice in which adiponectin was downregulated.
      Taken together, these results suggested that LGI3 may participate in adipose
      tissue homeostasis by negatively regulating adiponectin.

PMID- 23548728
TI  - Increased sex hormone-binding globulin levels in children and adolescents with
      thyrotoxicosis.
AB  - BACKGROUND: Thyrotoxicosis is a rare condition in pediatric patients, and optimal
      treatment can be difficult to achieve in some children. To our knowledge, no
      studies have evaluated sex hormone-binding globulin (SHBG) levels in hyperthyroid
      children and adolescents in relation to age- and gender-related normative data.
      METHODS: SHBG serum levels were determined before and after 4 months of
      antithyroid therapy (ATT) in 10 children and adolescents with Graves' disease. A
      total of 903 healthy children and adolescents served as controls. RESULTS: Serum
      SHBG levels were elevated (>2 SD) at diagnosis in all hyperthyroid children but
      normalized rapidly following ATT. At diagnosis, median SHBG was +2.51 SD
      (interquartile range 2.20-3.27) compared to healthy children without thyroid
      illness, and it declined significantly during ATT (-0.16 SD, -0.66 to 1.64; p <
      0.05). CONCLUSION: This is the first study to demonstrate that serum SHBG levels
      are markedly increased in children with Graves' disease, and we suggest that SHBG
      may be an additional marker of thyroid hormone action in children, as has been
      shown in adults.

PMID- 23548729
TI  - Unstaged cancer in a population-based registry: prevalence, predictors and
      patient prognosis.
AB  - PURPOSE: Information on cancer stage at diagnosis is critical for population
      studies investigating cancer care and outcomes. Few studies have examined the
      factors which impact (1) staging or (2) outcomes for patients who are registered
      as having unknown stage. This study investigated (1) the prevalence of unknown
      stage at diagnosis on the New Zealand Cancer Registry (NZCR); (2) explored
      factors which predict unknown stage; (3) described receipt of surgery and (4)
      survival outcomes for patients with unknown stage. METHODS: Patients diagnosed
      with the most prevalent 18 cancers between 2006 and 2008 (N=41,489) were
      identified from the NZCR, with additional data obtained from mortality and
      hospitalisation databases. Logistic and Cox regression were used to investigate
      predictors of unknown stage and patient outcomes. RESULTS: (1) Three distinct
      groups of cancers were found based on proportion of patients with unknown stage
      (low=up to 33% unknown stage; moderate=33-64%; high=65%+). (2) Increasing age was
      a significant predictor of unknown stage (adjusted odds ratios [ORs]: 1.18-1.24
      per 5-year increase across groups). Patients with substantive comorbidity were
      more likely to have unknown stage but only for those cancers with a low (OR=2.65
      [2.28-3.09]) or moderate (OR=1.17 [1.03-1.33]) proportion of patients with
      unknown stage. (3) Patients with unknown stage were significantly less likely to
      have received definitive surgery than those with local or regional disease across
      investigated cancers. (4) Patients with unknown stage had 28-day and 1-year
      survival which was intermediate between regional and distant disease. DISCUSSION:
      We found that stage completeness differs widely by cancer site. In many cases,
      the proportion of unknown stage on a population-based register can be explained
      by patient, service and/or cancer related factors.

PMID- 23548730
TI  - Wnt signaling during cochlear development.
AB  - Wnt signaling is a hallmark of all embryonic development with multiple roles at
      multiple developmental time points. Wnt signaling is also important in the
      development of several organs, one of which is the inner ear, where it
      participates in otic specification, the formation of vestibular structures, and
      the development of the cochlea. In particular, we focus on Wnt signaling in the
      auditory organ, the cochlea. Attempting to dissect the multiple Wnt signaling
      pathways in the mammalian cochlea is a challenging task due to limited expression
      data, particularly at proliferating stages. To offer predictions about Wnt
      activity, we compare cochlear development with that of other biological systems
      such as Xenopus retina, brain, cancer cells and osteoblasts. Wnts are likely to
      regulate development through crosstalk with other signaling pathways,
      particularly Notch and FGF, leading to changes in the expression of Sox2 and
      proneural (pro-hair cell) genes. In this review we have consolidated the known
      signaling pathways in the cochlea with known developmental roles of Wnts from
      other systems to generate a potential timeline of cochlear development. 

PMID- 23548732
TI  - A comparison of scan and focal sampling for the description of wild primate
      activity, diet and intragroup spatial relationships.
AB  - We used data collected during two concurrent studies of black howler monkeys
      (Alouatta pigra) in Palenque National Park, Mexico, to compare systematically
      three methods of behavioral data collection [group activity scan sampling (group
      scans), instantaneous focal individual sampling (instantaneous focals) and
      continuous focal individual sampling (continuous focals)] and three methods of
      proximity data collection [group proximity scan sampling (group proximity scans),
      focal individual proximity scan sampling (focal proximity scans) and
      instantaneous focal individual nearest neighbor sampling (focal nearest neighbor
      samples)]. We conducted pairwise comparisons of data among methods using Pearson
      correlations and one-sample t tests. A series of Kruskal-Wallis tests were
      performed to compare the activity and proximity patterns of adult males, adult
      females and juveniles described by each method. The three behavioral data
      collection methods generally provided similar information about activity and
      diet. However, important differences for both activity and proximity data existed
      among methods. Instantaneous focals overestimated the percentage of time spent in
      social interactions, while group scans overestimated time spent moving and
      underestimated time spent feeding. Group proximity scans and focal proximity
      scans provided similar spatial data, while focal nearest neighbor samples were
      more appropriate for determining the influence of one individual on another at
      any given moment. These biases suggest the importance of deliberate method
      selection during project design and highlight the need for taking methods into
      account when comparing studies.

PMID- 23548734
TI  - Test-retest stability of the Onset of Depression Inventory.
AB  - BACKGROUND: The 'Onset of Depression Inventory' (ODI) is a patient interview
      developed for systematically registering the speed of onset of depression. The
      ODI might contribute to the detection of hidden bipolarity because in previous
      studies a more rapid depression onset was found in patients with bipolar compared
      to unipolar depression. The aim of this study was to evaluate the test-retest
      stability of the ODI. Patients were asked concerning the speed of onset at the
      time of hospitalization and again before discharge. SAMPLING AND METHODS: Test
      retest stability of the ODI was investigated in 37 patients with a depressive
      episode. Each patient was interviewed concerning his present depressive episode
      by the same person at two different time points. Severity of depression at the
      different time points was assessed using the Hamilton Depression Rating Scale
      (HAMD-17) and the Inventory of Depressive Symptomatology (IDS-C). RESULTS: The
      speed of onset as assessed with the ODI showed good test-retest stability (rho =
      0.83, p < 0.001). This parameter was not influenced by changes in depression
      severity. CONCLUSIONS: The ODI allows reliable assessment of the speed of onset
      of depressive episodes. The instrument might be useful for the detection of
      hidden bipolarity.

PMID- 23548733
TI  - A simple score to predict survival with dementia in the general population.
AB  - BACKGROUND/AIMS: This study was designed to develop a practical risk score for
      predicting 5-year survival after the diagnosis of dementia. METHODS: Using the
      Paquid Study (prospective, population-based, long-term cohort study), we created
      a prognosis score with incident cases of dementia and validated it in another
      prospective, population-based, long-term cohort study, the Three City Study. -
      RESULTS: Among the 3,777 subjects enrolled in the Paquid Study, 454 incident
      cases of dementia were included in this study. After a 5-year follow-up period,
      319 (70.3%) were deceased. The score was constructed from three independent
      prognostic variables (gender, age at diagnosis and number of ADL restricted). The
      discriminant ability of the score was good with a c index of 0.754. Sensitivity
      was 64.7% and specificity 76.3%. In the validation cohort, the discriminant
      ability of the prognostic score with c statistics was 0.700. Sensitivity was
      26.3% and specificity 95.4%. CONCLUSIONS: The prognostic factors selected in the
      predictive model are easily assessable, so this simple score could provide
      helpful information for the management of dementia, particularly to identify
      patients with duration of the disease greater than 5 years.

PMID- 23548731
TI  - The role of Atonal transcription factors in the development of mechanosensitive
      cells.
AB  - Mechanosensation is an evolutionarily ancient sensory modality seen in all main
      animal groups. Mechanosensation can be mediated by sensory neurons or by
      dedicated receptor cells that form synapses with sensory neurons. Evidence over
      the last 15-20 years suggests that both classes of mechanosensory cells can be
      specified by the atonal class of basic helix-loop-helix transcription factors. In
      this review we discuss recent work addressing how atonal factors specify
      mechanosensitive cells in vertebrates and invertebrates, and how the redeployment
      of these factors underlies the regeneration of mechanosensitive cells in some
      vertebrate groups. 

PMID- 23548735
TI  - The impact of self-reported psychological stress levels on changes to peripheral
      blood immune biomarkers in recreational marathon runners during training and
      recovery.
AB  - OBJECTIVE: Marathon training is both physically and psychologically stressful,
      both of which can lead to altered immunity. The purpose of this study was to
      determine if the overall immunoregulatory changes associated with the physical
      stress of marathon training are affected by psychological stress. METHODS:
      Nineteen recreational marathoners completed the Perceived Stress Scale (PSS),
      State-Trait Anxiety Inventory (STAI) and Penn State Worry Questionnaire (PSWQ),
      and had levels of T cell subpopulations and cytokine (IFNgamma, IL4 and IL10)
      production determined 4 weeks before (baseline), 24-48 h before (prerace) and 1
      week after (recovery) participation in a marathon. RESULTS: PSS scores decreased
      at the prerace visit compared to baseline and remained low at recovery. Compared
      to baseline, there were significant changes to numerous immune measures at the
      prerace visit, including decreases in Th1/Th2 ratio, Tc1/Tc2 ratio, Tr1 and Th3
      cell populations as well as decreases in IFNgamma/IL4 cytokine ratio and IL10
      production. Most immune parameters had returned to near baseline values at the
      recovery visit. Higher levels of perceived stress, anxiety and worry exacerbated
      many of the alterations in immunity that were observed at the prerace visit.
      Higher levels of perceived stress and worry had significant effects on changes to
      Treg, IL4 production and the IFNgamma/IL4 cytokine ratio. Stress had an
      additional impact on changes in IL10 production. High anxiety levels resulted in
      significant changes to Treg, Tr1 and Th3. CONCLUSION: These data suggest that
      recreational marathon runners with higher levels of psychological stress may be
      more at risk for the immune alterations that are common during periods of
      prolonged physical training.

PMID- 23548736
TI  - Climate change adaptation: weighing strategies for heat-related health
      challenges.

PMID- 23548737
TI  - Modernizing methodology for the WHO assessment of substances for the
      international drug control conventions.
AB  - BACKGROUND: The WHO Executive Board revised the guidance that governs the
      procedures for the WHO review of psychoactive substances for international drug
      control in 2010. To meet the standards defined in these guidelines, the current
      evaluation methodology at WHO must be an evidence-based assessment. METHODS: We
      describe the history of substance evaluation from 1912 to the present and the
      development of the evaluation methods over time including a description of the
      current assessment system, using reports from WHO and its predecessor, the League
      of Nations. Furthermore, we describe the current review system. RESULTS: We found
      that some substances under international control were never reviewed; other
      substances were reviewed decades ago. CONCLUSIONS: We argue that assessments do
      not have unlimited validity, and therefore, substances need to be re-assessed
      periodically, as already recommended by the Expert Committee on Drug Dependence
      in 1982. We propose that the evaluation time be shortened; that the influence of
      the route of administration and/or dosage form of the preparation is considered
      in the evaluation; and we recommend studying national and regional assessment
      systems and adopting their best practices. With this article, we make a case for
      the inclusion of systematic review and other methods of comprehensive analysis of
      substance evaluation to arrive at a process of equal rigour and quality as
      already applied by WHO for the development of treatment guidelines.

PMID- 23548739
TI  - The risks and benefits of antidepressants to treat pediatric-onset depression and
      anxiety disorders: a developmental perspective.

PMID- 23548738
TI  - Prevalence of pre-end-stage renal disease care and associated outcomes among
      urban, micropolitan, and rural dialysis patients.
AB  - BACKGROUND/AIMS: Pre-end-stage renal disease (ESRD) care is associated with
      improved outcomes among patients receiving dialysis. It is unknown what
      proportion of US micropolitan and rural dialysis patients receive pre-ESRD care
      and benefit from such care when compared to urban. METHODS: A retrospective
      cohort study was performed using data from the US Renal Data System. Patients
      >=18 years old who initiated dialysis in 2006 and 2007 were classified as rural,
      micropolitan or urban and the prevalence of pre-ESRD care (early nephrology care
      >6 months, permanent vascular access, -dietary education) was determined using
      the medical evidence report. The association of pre-ESRD care with dialysis
      mortality and transplantation was assessed using Cox regression with
      stratification for geographic residence. RESULTS: Of 204,463 dialysis patients,
      80% were urban, 10.2% were micropolitan and 9.8% were rural. Overall attainment
      of pre-ESRD care was poor. After adjustment, there were no significant geographic
      differences in attainment of early nephrology care or permanent dialysis access.
      Receiving care reduced all-cause mortality and increased the likelihood of
      transplantation to a similar degree regardless of geographic residence. Both
      micropolitan and rural patients received less dietary education (relative risk =
      0.80, 95% CI = 0.76-0.84 and relative risk = 0.85, 95% CI = 0.80-0.89,
      respectively). CONCLUSION: Among patients who receive dialysis, the prevalence of
      early nephrology care and permanent dialysis access is poor and does not vary by
      geographic residence. Micropolitan and rural patients receive less dietary
      education despite an observed mortality benefit, suggesting that barriers may
      exist to quality dietary care in more remote locations.

PMID- 23548740
TI  - Nutritional genetics: the case of alcohol and the MTHFR C677T polymorphism in
      relation to homocysteine in a black South African population.
AB  - BACKGROUND/AIMS: It is unknown whether the effect of alcohol consumption on
      homocysteine (Hcy) is modulated by the methylenetetrahydrofolate reductase
      (MTHFR) C677T. We explored this hypothesized effect by analyzing cross-sectional
      data of 1,827 black South Africans. METHODS: Total Hcy concentrations were
      determined by fluorescence polarization immunoassay and the genotype through
      polymerase chain reaction-based RFLP analysis. RESULTS: Subjects harboring the
      677 TT genotype had the highest Hcy. Among subjects harboring the 677 CC
      genotype, men had higher Hcy (p = 0.04). Age and gamma-glutamyltransferase (GGT)
      correlated best (r = 0.26 and r = 0.27; p < 0.05), while the percentage
      carbohydrate-deficient transferrin and the B vitamins correlated weakly (r < 0.1;
      p < 0.05) with Hcy. Hcy was positively associated with the reported alcohol
      intake (p <= 0.01). There was no interaction between alcohol consumption and the
      MTHFR 677 CC or CT genotypes (p > 0.05) for Hcy concentrations; however, an
      interaction was determined for GGT and the MTHFR genotype (p = 0.02). Age, GGT,
      gender, MTHFR and vitamin B6 explained 16.8% of the variation in Hcy (p < 0.01).
      CONCLUSION: The determined interactions might result in differences in the risk
      conveyed through Hcy with regard to disease development in those with unfavorable
      GGT concentrations.

PMID- 23548741
TI  - Quality of nuchal translucency measurements correlates with broader aspects of
      program rigor and culture of excellence.
AB  - INTRODUCTION: To determine if nuchal translucency (NT) quality correlates with
      the extent to which clinics vary in rigor and quality control. METHODS: We
      correlated NT performance quality (bias and precision) of 246,000 patients with
      two alternative measures of clinic culture - % of cases for whom nasal bone (NB)
      measurements were performed and % of requisitions correctly filled for race
      ethnicity and weight. RESULTS: When requisition errors occurred in <5% of cases,
      the average MoM (multiple of the median) was 0.97. When >5% (33%), the curve
      lowered to 0.93 MoM (p < 0.001) with both bias and precision of measurements
      impaired. Likewise, for centers with NB >90%, MoM was 0.99 compared to those <10%
      at 0.93 (p < 0.001). Precision and bias were highly correlated (p < 0.001).
      CONCLUSIONS: Rigor in NT measurements has improved, but the discussion has been
      confined to individuals. Progressive educational and remediation strategies need
      to expand to a second dimension - clinics themselves. Cross-clinic variation in
      NT quality exists independent of individual variation in NT quality, and two
      divergent indices of program rigor are associated with NT quality. Quality
      control must be program wide, and to effect continued improvement in the quality
      of NT results across time, the cultures of clinics must become a target for
      intervention.

PMID- 23548742
TI  - Strain magnitude-dependent calcific marker expression in valvular and vascular
      cells.
AB  - Aortic valve disease and atherosclerosis tend to coexist in most patients with
      cardiovascular disease; however, the causes and mechanisms of disease development
      in heart valves are still not clearly understood. To understand the contributions
      of the magnitude of cyclic strain (5% hypotension, 10% physiological, and 15%
      hypertension) in calcification, we used a model system of tissue-engineered
      collagen gels containing human aortic smooth muscle cells and human aortic
      valvular interstitial cells, both isolated from noncalcific heart transplant
      tissue. The compacted collagen gels were cultured in osteogenic media for 3 weeks
      in a custom-designed bioreactor and all assessments were performed at the end of
      the culture period. The major finding of this study is that bone morphogenic
      protein (BMP)-2 and BMP-4 and transforming growth factor-beta1 mRNA expression
      significantly changed in response to the magnitude of applied strain in valvular
      cells, while the lowest expression was observed for the representative
      physiological strain. On the other hand, mRNA expression in vascular cells did
      not vary in response to the magnitude of strain. Regarding BMP-2 and BMP-4
      protein expression determined by immunostaining, trends were similar to mRNA
      expression in vascular and valvular cells, where only valvular cells showed a
      varied protein expression depending on the magnitude of the strain applied. Our
      results suggest that cellular differences exist between vascular and valvular
      cells in their response to altered levels of cyclic strain during calcification.

PMID- 23548743
TI  - The rice resistance protein pair RGA4/RGA5 recognizes the Magnaporthe oryzae
      effectors AVR-Pia and AVR1-CO39 by direct binding.
AB  - Resistance (R) proteins recognize pathogen avirulence (Avr) proteins by direct or
      indirect binding and are multidomain proteins generally carrying a nucleotide
      binding (NB) and a leucine-rich repeat (LRR) domain. Two NB-LRR protein-coding
      genes from rice (Oryza sativa), RGA4 and RGA5, were found to be required for the
      recognition of the Magnaporthe oryzae effector AVR1-CO39. RGA4 and RGA5 also
      mediate recognition of the unrelated M. oryzae effector AVR-Pia, indicating that
      the corresponding R proteins possess dual recognition specificity. For RGA5, two
      alternative transcripts, RGA5-A and RGA5-B, were identified. Genetic analysis
      showed that only RGA5-A confers resistance, while RGA5-B is inactive. Yeast two
      hybrid, coimmunoprecipitation, and fluorescence resonance energy transfer
      fluorescence lifetime imaging experiments revealed direct binding of AVR-Pia and
      AVR1-CO39 to RGA5-A, providing evidence for the recognition of multiple Avr
      proteins by direct binding to a single R protein. Direct binding seems to be
      required for resistance as an inactive AVR-Pia allele did not bind RGA5-A. A
      small Avr interaction domain with homology to the Avr recognition domain in the
      rice R protein Pik-1 was identified in the C terminus of RGA5-A. This reveals a
      mode of Avr protein recognition through direct binding to a novel, non-LRR
      interaction domain.

PMID- 23548744
TI  - PHYTOCHROME INTERACTING FACTOR3 associates with the histone deacetylase HDA15 in
      repression of chlorophyll biosynthesis and photosynthesis in etiolated
      Arabidopsis seedlings.
AB  - PHYTOCHROME INTERACTING FACTOR3 (PIF3) is a key basic helix-loop-helix
      transcription factor of Arabidopsis thaliana that negatively regulates light
      responses, repressing chlorophyll biosynthesis, photosynthesis, and
      photomorphogenesis in the dark. However, the mechanism for the PIF3-mediated
      transcription regulation remains largely unknown. In this study, we found that
      the REDUCED POTASSIUM DEPENDENCY3/HISTONE DEACETYLASE1-type histone deacetylase
      HDA15 directly interacted with PIF3 in vivo and in vitro. Genome-wide
      transcriptome analysis revealed that HDA15 acts mainly as a transcriptional
      repressor and negatively regulates chlorophyll biosynthesis and photosynthesis
      gene expression in etiolated seedlings. HDA15 and PIF3 cotarget to the genes
      involved in chlorophyll biosynthesis and photosynthesis in the dark and repress
      gene expression by decreasing the acetylation levels and RNA Polymerase II
      associated transcription. The binding of HDA15 to the target genes depends on the
      presence of PIF3. In addition, PIF3 and HDA15 are dissociated from the target
      genes upon exposure to red light. Taken together, our results indicate that PIF3
      associates with HDA15 to repress chlorophyll biosynthetic and photosynthetic
      genes in etiolated seedlings.

PMID- 23548746
TI  - A hybrid nanostructure array for gas sensing with ultralow field ionization
      voltage.
AB  - We fabricate a unique hybrid nanostructure array for gas sensing based on the
      polarization mechanism at the nanoscale. It is shown that with platinum
      nanocrystallites on the top of each nanoneedle, this array can work at ultralow
      voltages (less than 10 V) as a field ionization gas sensor. We believe that the
      polarized platinum brings about a local enhanced electrical field, leading to the
      direct field ionization of gas molecules, which is confirmed by calculations of
      the charge accumulation and electrical field distribution.

PMID- 23548745
TI  - Increased alpha-fetoprotein serum level is predictive for survival and recurrence
      of hepatocellular carcinoma in non-cirrhotic livers.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) may be diagnosed in the absence of
      cirrhosis. However, little is known about prognostic factors for the survival of
      HCC patients with a non-cirrhotic liver in the absence of well-established risk
      factors. METHOD: Survival rates and risk factors for survival and recurrence were
      analysed in all patients diagnosed between 2000 and 2010 with HCC in a non
      cirrhotic liver and in the absence of well-established risk factors. RESULTS:
      Ninety-four patients were analysed. Treatment with curative intent consisted of
      surgical resection in 43 patients (46%) and radiofrequency ablation in 4 patients
      (4%). In patients treated with curative intent and alive 30 days after treatment
      (n = 40), 1- and 5-year overall survival rates were 95 and 51%, respectively.
      Patients with a high preoperative alpha-fetoprotein (AFP) serum level, the
      presence of microvascular invasion in the resected specimen, a complicated
      postoperative course and a major resection, due to a greater tumour volume, had a
      significantly worse outcome and a higher recurrence rate. In multivariate
      analysis, a high AFP serum level at presentation was significantly associated
      with recurrence and a worse survival. CONCLUSION: HCC presenting in a non
      cirrhotic liver in the absence of well-established risk factors has a poor
      prognosis. Increased AFP serum levels are significantly associated with clinical
      outcome.

PMID- 23548747
TI  - Carotid intima-media thickness: a novel inflammatory marker which should not be
      assessed alone!

PMID- 23548748
TI  - Public awareness of early symptoms of stroke and information sources about stroke
      among the general Japanese population: the Acquisition of Stroke Knowledge Study.
AB  - BACKGROUND: It is important that the general population be aware of the early
      symptoms, since it has been shown that early arrival to hospitals leads better
      prognosis of stroke patients. However, the general population is not well
      informed about the early symptoms of stroke. This study was conducted to clarify
      which stroke symptoms are less well known and which information sources are
      related to awareness of stroke symptoms. METHODS: A multiple-choice, mail-in
      survey involving 5,540 randomly selected residents, aged 40-74 years, of 3 cities
      in Japan was conducted. Their knowledge about stroke symptoms and their
      information sources were surveyed; information sources were classified as mass
      media (television/newspaper/radio) and personal communication sources
      (posters/leaflets/internet/health professionals/family and/or friends).
      'Awareness' was defined as selecting all 5 of the correct stroke symptoms from
      among 10 listed symptoms with decoy choices. The estimated fraction of the
      possible impact due to each source on the whole population was also calculated by
      odds ratios (ORs) and the proportion of respondents who selected each source
      (Pe). The combined effects of mass media and personal communication sources on
      awareness were also assessed. RESULTS: Of the 5,540 residents, only 23% selected
      all 5 correct symptoms. Visual disturbance was the least known of the 5 symptoms
      (35%). All sources were positively related to awareness, with ORs (Pe) of:
      television, 1.58 (72.5%); newspaper, 1.79 (48.0%); radio, 1.74 (13.3%); posters,
      1.73 (7.6%); leaflets, 1.50 (24.7%); Internet, 1.66 (5.6%); health professionals,
      1.33 (34.8%), and family/friends, 1.21 (44.6%). The estimated fraction of the
      possible impact due to each source was higher for mass media (television, 0.31
      and newspaper, 0.28) than personal communication sources (Internet, 0.04 and
      leaflets, 0.12). Mass media only and mass media/personal communication sources
      were significantly associated (ORs: 1.66, 2.75, respectively). CONCLUSIONS: As a
      single method of public education, television could be the most effective
      strategy. Moreover, the combined approach involving mass media and personal
      communication sources might have a synergistic effect. Less well-known symptoms,
      such as visual disturbances, should be noted in public education campaigns.

PMID- 23548750
TI  - Indoleamine 2,3-dioxygenases with very low catalytic activity are well conserved
      across kingdoms: IDOs of Basidiomycota.
AB  - Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme and is found
      in animals, fungi and bacteria. In fungi, its primary role is to supply
      nicotinamide adenine dinucleotide (NAD(+)) via the kynurenine pathway. A number
      of organisms possess more than one IDO gene, for example, mammals have IDO1 and
      IDO2 genes. We previously reported that the Pezizomycotina fungi commonly possess
      three types of IDO genes, IDOalpha, IDObeta and IDOgamma. In this study, we
      surveyed the nature of IDO genes from Basidiomycota fungi, which are categorized
      into three subphyla (Agaricomycotina, Pucciniomycotina and Ustilaginomycotina).
      The Agaricomycotina fungi generally have three types of IDO genes (IDOa, IDOb and
      IDOc), which are distinct from Pezizomycotina three isozymes. Pucciniomycotina
      and Ustilaginomycotina species possess two types of IDO; one forms a monophyletic
      clade with Agaricomycotina IDOs in the phylogenetic tree, these IDOs are referred
      to as "typical Basidiomycota IDOs". The other is IDOgamma, which showed more than
      40% identity with Pezizomycotina and ciliate IDOgamma. We previously demonstrated
      that IDO2 in mammals and IDOgamma in Perzizomycotina fungi have much lower
      catalytic efficiencies in an in vitro assay, compared with the other IDO isoforms
      found in the respective species. We have developed a functional assay to
      determine whether particular IDO enzymes have sufficient enzymatic activity to
      rescue a yeast strain where IDO-deletion has rendered it auxotrophic for
      nicotinic acid. IDOalpha and IDObeta showed comparable catalytic efficiency, both
      of them could function in the Pezizomycotina fungal L-Trp metabolism. The
      catalytic efficiency and functional capacity of the Basidiomycota IDOa and IDOb
      were similar to Pezizomycotina IDOalpha/IDObeta. We found that Basidiomycota IDOc
      could not rescue the nicotinic acid auxotroph, similar to other IDO enzymes with
      low catalytic efficiency (mammalian IDO2 and most fungal IDOgamma). Our study
      suggests that some fungal IDO enzymes function in tryptophan metabolism and
      NAD(+) supply. In contrast, other IDO enzymes do not possess sufficient Trp
      metabolising capacity to supply NAD(+). Although the role of these low catalytic
      efficiency IDOs is not clear, it is interesting to note that IDO enzymes
      possessing these characteristics have evolved across different kingdoms. 

PMID- 23548751
TI  - Variations in the vitamin D-binding protein (DBP) gene are related to lower 25
      hydroxyvitamin D levels in healthy girls: a cross-sectional study.
AB  - BACKGROUND/AIMS: Vitamin D deficiency has been recognized as a worldwide epidemic
      affecting several pediatric and adolescent populations. We determined the
      genotype and haplotype distribution of the rs4588 and rs7041 polymorphisms of the
      GC gene encoding vitamin D-binding protein (DBP) and investigated the
      associations between these gene variants and their haplotypes with 25
      hydroxyvitamin D [25(OH)D] levels in girls from South Brazil. METHODS: Cross
      sectional study including 198 apparently healthy girls aged 10-18 years. Plasma
      levels of 25(OH)D were assessed by radioimmunoassay. Participants were genotyped
      for rs4588 and rs7041 by real-time PCR, with allelic discrimination assays.
      RESULTS: Mean chronological age and BMI percentile were 13.17 +/- 1.74 years and
      57.81 +/- 29.03, respectively. Sufficient circulating 25(OH)D levels (>=30 ng/ml)
      were found in 9.1% of the overall group, insufficient levels (20-29.9 ng/ml) in
      59.6%, and deficient levels (<20 ng/ml) in 31.3%. The AA genotype of rs4588, TT
      genotype of rs7041 and CT-AT/AT-AT (GC 1f-2/2-2) diplotypes were significantly
      associated with lower 25(OH)D levels, even after adjustment for age and season at
      the time of blood collection. CONCLUSIONS: The GC gene genotype may be related to
      the susceptibility to low 25(OH)D levels in female children and adolescents.

PMID- 23548749
TI  - PD-1 coinhibitory signals: the link between pathogenesis and protection.
AB  - In the majority of HIV-1 infected individuals, the adaptive immune response
      drives virus escape resulting in persistent viremia and a lack of immune-mediated
      control. The expression of negative regulatory molecules such as PD-1 during
      chronic HIV infection provides a useful marker to differentiate functional memory
      T cell subsets and the frequency of T cells with an exhausted phenotype. In
      addition, cell-based measurements of virus persistence equate with activation
      markers and the frequency of CD4 T cells expressing PD-1. High-level expression
      of PD-1 and its ligands PD-L1 and PD-L2 are found on hematopoietic and non
      hematopoietic cells, and are upregulated by chronic antigen stimulation, Type 1
      and Type II interferons (IFNs), and homeostatic cytokines. In HIV infected
      subjects, PD-1 levels on CD4 and CD8 T cells continue to remain high following
      combination anti-retroviral therapy (cART). System biology approaches have begun
      to elucidate signal transduction pathways regulated by PD-1 expression in CD4 and
      CD8 T cell subsets that become dysfunctional through chronic TCR activation and
      PD-1 signaling. In this review, we summarize our current understanding of
      transcriptional signatures and signal transduction pathways associated with
      immune exhaustion with a focus on recent work in our laboratory characterizing
      the role of PD-1 in T cell dysfunction and HIV pathogenesis. We also highlight
      the therapeutic potential of blocking PD-1-PD-L1 and other immune checkpoints for
      activating potent cellular immune responses against chronic viral infections and
      cancer. 

PMID- 23548752
TI  - Younger siblings, C-reactive protein, and risk of age-related macular
      degeneration.
AB  - In this study, we examined the relationship between exposure to siblings and 1)
      the risk of age-related macular degeneration (AMD) and 2) C-reactive protein
      levels. We retrospectively analyzed pooled cross-sectional data from 2 studies:
      the Cardiovascular Health and Age-Related Maculopathy Study (2001-2002) and the
      Age-Related Maculopathy Statin Study (2004-2006). Associations between number of
      siblings and AMD were assessed by using multinomial logistic regression.
      Associations between number of siblings and C-reactive protein levels were
      examined by using a generalized linear model for gamma distribution. A higher
      number of younger siblings was associated with significantly lower odds of early
      AMD in those with a family history of AMD (odds ratio = 0.2, 95% confidence
      interval: 0.1, 0.8) (P = 0.022) but was unrelated to AMD for those who had no
      family history of the disease (odds ratio = 1.0, 95% confidence interval: 0.9,
      1.2) (P = 0.874). A higher number of younger siblings correlated with lower C
      reactive protein levels (beta = -0.19, 95% confidence interval: -0.38, -0.01) (P
      = 0.036). This supports the theory that immune modulation contributes to AMD
      pathogenesis and suggests that exposure to younger siblings might be protective
      when there is a family history of AMD. 

PMID- 23548753
TI  - Iodine supplementation during pregnancy and infant neuropsychological
      development. INMA Mother and Child Cohort Study.
AB  - Iodine supplementation during pregnancy is a common practice in developed
      countries. However, scant evidence is available regarding the safety and
      effectiveness of maternal iodine supplementation with regard to child
      neuropsychological development. We previously reported an inverse association
      between iodine supplementation and the psychomotor development of infants in a
      birth cohort from Valencia, Spain. In the present study, we assessed this
      association in a wider sample of mother and child pairs from 3 other regions in
      Spain. Neuropsychological development was assessed using the Bayley Scales of
      Infant Development in 1,519 infants (median age, 16 months) between 2006 and
      2009. In multivariate analyses, maternal consumption of 150 MUg/day or more of
      iodine from supplements was related to a 1.5-fold increase in the odds of a
      psychomotor score less than 85 (95% confidence interval: 0.8, 2.9) and to a 1.7
      fold increase in the odds of a mental score less than 85 (95% confidence
      interval: 0.9, 3.0). Findings previously reported in the Valencia cohort were
      only partially verified. The results of the present study suggest that, at least
      in these regions, iodine supplementation does not improve infant
      neuropsychological development at 1 year of age. Further research is needed on
      the risks and benefits of supplementary iodine for both maternal thyroid function
      and child neurodevelopment. 

PMID- 23548754
TI  - Hope-Simpson's progressive immunity hypothesis as a possible explanation for
      herpes zoster incidence data.
AB  - Varicella-zoster virus (VZV) is the causative agent of both varicella
      (chickenpox) and herpes zoster (HZ) (shingles). After varicella infection, the
      virus remains dormant in the host's dorsal ganglia and can reactivate due to
      waning cell-mediated immunity, causing HZ. Exposure of varicella-immune persons
      to VZV may boost the host's immune response, resulting in a protective effect
      against HZ. In this study, we used mathematical models of VZV transmission and HZ
      development to test the biological hypothesis of "progressive immunity,"
      originally proposed by Hope-Simpson (Proc R Soc Med. 1965;58:9-20), that cell
      mediated protection against HZ increases after each episode of exposure to VZV.
      Predictions from a model incorporating such a hypothesis were compared with those
      of other concurrent models proposed for explaining HZ epidemiology. The
      progressive immunity model fits significantly better the age profile of HZ
      incidence for Finland (years 2000-2006), Italy (2003-2005), Spain (1997-2004),
      and the United Kingdom (1991-1992), suggesting that this mechanism may be
      critical in shaping HZ patterns. The model thus validated is an alternative to
      VZV models currently used to evaluate the impact of mass immunization programs
      for varicella and therefore extends the range of tools available to assist policy
      makers with the present decision paralysis on the introduction of vaccination.

PMID- 23548755
TI  - Using a nonparametric multilevel latent Markov model to evaluate diagnostics for
      trachoma.
AB  - In disease control or elimination programs, diagnostics are essential for
      assessing the impact of interventions, refining treatment strategies, and
      minimizing the waste of scarce resources. Although high-performance tests are
      desirable, increased accuracy is frequently accompanied by a requirement for more
      elaborate infrastructure, which is often not feasible in the developing world.
      These challenges are pertinent to mapping, impact monitoring, and surveillance in
      trachoma elimination programs. To help inform rational design of diagnostics for
      trachoma elimination, we outline a nonparametric multilevel latent Markov
      modeling approach and apply it to 2 longitudinal cohort studies of trachoma
      endemic communities in Tanzania (2000-2002) and The Gambia (2001-2002) to provide
      simultaneous inferences about the true population prevalence of Chlamydia
      trachomatis infection and disease and the sensitivity, specificity, and
      predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates
      were obtained by using data collected before and after mass azithromycin
      administration. Such estimates are particularly important for trachoma because of
      the absence of a true "gold standard" diagnostic test for C. trachomatis.
      Estimated transition probabilities provide useful insights into key epidemiologic
      questions about the persistence of disease and the clearance of infection as well
      as the required frequency of surveillance in the post-elimination setting.

PMID- 23548756
TI  - Association of injurious falls with disability outcomes and nursing home
      admissions in community-living older persons.
AB  - Little is known about the deleterious effects of injurious falls relative to
      those of other disabling conditions or whether these effects are driven largely
      by hip fractures. From a cohort of 754 community-living elders of New Haven,
      Connecticut, we matched 122 hospitalizations for an injurious fall (59 hip
      fracture and 63 other fall-related injuries) to 241 non-fall-related
      hospitalizations. Participants (mean age: 85.7 years) were evaluated monthly for
      disability in 13 activities and admission to a nursing home from 1998 to 2010.
      For both hip-fracture and other fall-related injuries, the disability scores were
      significantly greater during each of the first 6 months after hospitalization
      than for the non-fall-related admissions, with adjusted risk ratios at 6 months
      of 1.5 (95% confidence interval (CI): 1.3, 1.7) for hip fracture and 1.4 (95% CI:
      1.2, 1.6) for other fall-related injuries. The likelihood of having a long-term
      nursing home admission was considerably greater after hospitalization for a hip
      fracture and other fall-related injury than for a non-fall-related reason, with
      adjusted odds ratios of 3.3 (95% CI: 1.3, 8.3) and 3.2 (95% CI: 1.3, 7.8),
      respectively. Relative to other conditions leading to hospitalization, hip
      fracture and other fall-related injuries are associated with worse disability
      outcomes and a higher likelihood of long-term nursing home admissions. 

PMID- 23548757
TI  - Is hepcidin a new cardiovascular risk marker in polycystic ovary syndrome?
AB  - BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is associated with reproductive
      and metabolic abnormalities and carries a number of cardiovascular risk factors.
      Low-grade chronic inflammation has been thought to play a role in the
      pathogenesis of atherosclerosis and PCOS patients have an increased rate of
      subclinical inflammation. In the present study, considering the major role that
      hepcidin plays in the regulation of iron metabolism and as an inflammatory
      marker, we investigated hepcidin in PCOS patients and its role in predicting
      cardiovascular disease (CVD) development. METHODS: Forty patients with PCOS and
      40 age- and body mass index-matched healthy controls were included in the study.
      Iron metabolites, insulin resistance (IR), inflammatory markers and hepcidin
      levels were analyzed. RESULTS: IR parameters, inflammatory markers, iron
      parameters and hepcidin levels were similar between the PCOS and control groups.
      While the inflammatory markers were significantly high in the overweight and
      obese PCOS subgroup, the hepcidin levels were also high but this elevation was
      not statistically significant. CONCLUSION: Obesity is the principle mechanism of
      chronic inflammation and IR in PCOS patients. C-reactive protein and interleukin
      6 should be used to predict and follow the risk of CVD development in PCOS cases.
      Hepcidin may be used as an additional marker in the follow-up of PCOS patients in
      the future.

PMID- 23548758
TI  - Unclear relationship: prenatal but not concurrent bisphenol a exposure linked to
      lower weight and less fat.

PMID- 23548759
TI  - Guidelines for the recording and evaluation of pharmaco-sleep studies in man: the
      International Pharmaco-EEG Society (IPEG).
AB  - The International Pharmaco-EEG Society (IPEG) presents guidelines summarising the
      requirements for the recording and computerised evaluation of pharmaco-sleep data
      in man. Over the past years, technical and data-processing methods have advanced
      steadily, thus enhancing data quality and expanding the palette of sleep
      assessment tools that can be used to investigate the activity of drugs on the
      central nervous system (CNS), determine the time course of effects and
      pharmacodynamic properties of novel therapeutics, hence enabling the study of the
      pharmacokinetic/pharmacodynamic relationship, and evaluate the CNS penetration or
      toxicity of compounds. However, despite the presence of robust guidelines on the
      scoring of polysomnography -recordings, a review of the literature reveals
      inconsistent -aspects in the operating procedures from one study to another.
      While this fact does not invalidate results, the lack of standardisation
      constitutes a regrettable shortcoming, especially in the context of drug
      development programmes. The present guidelines are intended to assist
      investigators, who are using pharmaco-sleep measures in clinical research, in an
      effort to provide clear and concise recommendations and thereby to standardise
      methodology and facilitate comparability of data across laboratories.

PMID- 23548760
TI  - Feral swine brucellosis in the United States and prospective genomic techniques
      for disease epidemiology.
AB  - Brucellosis is a common infection of feral swine throughout the United States.
      With the recent expansion of feral swine populations across the country, this
      disease poses an increasing threat to agriculture and hunters. The standard
      approach to Brucella surveillance in feral swine has been serological testing,
      which gives an indication of past exposure and is a rapid method of determining
      populations where Brucella is present. More in-depth analyses require bacterial
      isolation to determine the Brucella species and biovar involved. Ultimately, for
      a comprehensive understanding of Brucella epizootiology in feral swine,
      incorporation of genotyping assays has become essential. Fortunately, the past
      decade has given rise to an array of genetic tools for assessing Brucella
      transmission and dispersal. This review aims to synthesize what is known about
      brucellosis in feral swine and will cover prospective genomic techniques that may
      be utilized to develop more complete understanding of the disease and its
      transmission history. 

PMID- 23548761
TI  - Renal involvement in AA amyloidosis: clinical outcomes and survival.
AB  - BACKGROUND: The natural history of AA amyloidosis is typically progressive,
      leading to multiple organ failure and death. We analyzed the etiology as well as
      clinical and laboratory features of patients with biopsy-proven AA amyloidosis
      and evaluated the ultimate outcome. METHODS: Seventy-three patients (24 female;
      mean age 41.85+/-15.89 years) were analyzed retrospectively. Demographic,
      clinical and laboratory features were studied and the outcome was assessed.
      RESULTS: Familial Mediterranean Fever and tuberculosis were the most frequent
      causes of amyloidosis. Mean serum creatinine and proteinuria at diagnosis were
      4.65+/-4.89 mg/dl and 8.04+/-6.09 g/day, respectively; and stage I, II, III, IV
      and V renal disease were present in 19.2%, 13.7%, 16.4%, 11%, and 39.7% of the
      patients, respectively. ESRD developed in 16 patients during the follow-up
      period. All of the ESRD patients started a dialysis programme. Thirty patients
      (41%) died during the follow-up period; median patient survival was 35.9+/-6.12
      months. Old age, tuberculosis etiology, advanced renal disease and low serum
      albumin levels were associated with a worse prognosis. Serum albumin was a
      predictor of mortality in logistic regression analysis. CONCLUSION: The ultimate
      outcome of the patients with AA amyloidosis is poor, possibly due to the late
      referral to the nephrology clinics. Early referral may be helpful to improve
      prognosis.

PMID- 23548762
TI  - The relation of uric acid to brain atrophy and cognition: the Rotterdam Scan
      Study.
AB  - BACKGROUND: Uric acid has been associated with focal vascular brain disease.
      However, it is unknown whether uric acid also relates to global brain changes
      such as brain atrophy. We therefore studied the relation of uric acid to brain
      atrophy and whether this is accompanied by worse cognitive function. METHODS: In
      814 persons of the population-based Rotterdam Study (mean age 62.0 years), we
      studied the relation of uric acid levels to brain tissue atrophy and cognition
      using linear regression models adjusted for age, sex and putative confounders.
      Brain atrophy was assessed using automated processing of magnetic resonance
      imaging. Cognition was assessed using a validated neuropsychological test battery
      and we computed compound scores of cognitive domains. RESULTS: Higher uric acid
      levels were associated with white matter atrophy [difference in Z-score of white
      matter volume per standard deviation increase in uric acid: -0.07 (95% CI: -0.12;
      -0.01)], but not with gray matter atrophy. This was particularly marked when
      comparing hyperuricemic to normouricemic persons [Z-score difference: -0.27 (
      0.43; -0.11)]. Worse cognition was primarily found in persons with hyperuricemia
      [-0.28 (-0.48; -0.08)]. CONCLUSIONS: Hyperuricemia is related to white matter
      atrophy and worse cognition.

PMID- 23548763
TI  - Pulmonary hypertension in renal disease: epidemiology, potential mechanisms and
      implications.
AB  - Pulmonary hypertension (PH) is highly prevalent in end-stage renal disease.
      Several observational studies, based on an echocardiographic diagnosis of PH,
      have suggested a prevalence of 30-60% and an association with increased mortality
      and poorer outcome following renal transplantation. The pathogenesis of PH in
      this population remains poorly understood. Reported associations include
      arteriovenous fistulae, cardiac dysfunction, fluid overload, bone mineral
      disorder and non-biocompatible dialysis membranes. However, due to the small
      numbers, the cross-sectional nature of the majority of studies in this field, and
      the reliance on echocardiography for the diagnosis of PH, no consistent
      association with any individual risk factor has been demonstrated. There is no
      difference in prevalence between patients receiving different dialysis modalities
      and emerging evidence suggests that the onset of the condition may precede
      dialysis treatment in many patients. Furthermore, little is known about the
      impact of the 'uraemic vasculopathy' on the pulmonary vasculature. Given the
      similarities between vascular changes in uraemia and those seen in pulmonary
      arterial hypertension, it is possible that a pulmonary vasculopathy may be
      present in a proportion of patients. There is a need for better understanding of
      the natural history and the pathogenesis of the condition which would help to
      individualise treatment of PH in end-stage renal disease. To enable such
      understanding, prospective adequately powered studies with an integrated
      investigational approach including right heart catheterisation are needed.

PMID- 23548764
TI  - Excessive mood elevation and behavioral activation with antidepressant treatment
      of juvenile depressive and anxiety disorders: a systematic review.
AB  - BACKGROUND: The prevalence, characteristics and implications of excessive arousal
      activation in children and adolescents treated with antidepressants for specific
      illnesses have not been systematically examined. METHODS: We compared reports of
      antidepressant trials (n = 6,767 subjects) in juvenile depressive (n = 17) and
      anxiety disorders (n = 25) for consensus-based indications of psychopathological
      mood elevation or behavioral activation. RESULTS: Rates of excessive arousal
      activation during treatment with antidepressants were at least as high in
      juvenile anxiety (13.8%) as depressive (9.79%) disorders, and much lower with
      placebos (5.22 vs. 1.10%, respectively; both p < 0.0001). The
      antidepressant/placebo risk ratio for such reactions in paired comparisons was
      3.50 (12.9/3.69%), and the meta-analytically pooled rate ratio was 1.7 (95%
      confidence interval: 1.2-2.2; both p <= 0.001). Overall rates for 'mania or
      hypomania', specifically, were 8.19% with and 0.17% without antidepressant
      treatment, with large drug/placebo risk ratios among depressive (10.4/0.45%) and
      anxiety (1.98/0.00%) disorder patients. CONCLUSIONS: Risks of excessive mood
      elevation during antidepressant treatment, including mania-hypomania, were much
      greater than with placebo, and similar in juvenile anxiety and depressive
      disorders. Excessive arousal-activation in children or adolescents treated with
      antidepressants for anxiety as well as depressive disorders calls for particular
      caution and monitoring for potential risk of future bipolar disorder.

PMID- 23548765
TI  - Evaluation of the alcohol use disorders identification test and the drug use
      disorders identification test among patients at a Norwegian psychiatric emergency
      ward.
AB  - High rates of substance use disorders (SUD) among psychiatric patients are well
      documented. This study explores the usefulness of the Alcohol Use Disorders
      Identification Test (AUDIT) and the Drug Use Disorders Identification Test
      (DUDIT) in identifying SUD in emergency psychiatric patients. Of 287 patients
      admitted consecutively, 256 participants (89%) were included, and 61-64%
      completed the questionnaires and the Mini-International Neuropsychiatric
      Interview (MINI), used as the reference standard. Both AUDIT and DUDIT were valid
      (area under the curve above 0.92) and reliable (Cronbach's alpha above 0.89) in
      psychotic and nonpsychotic men and women. The suitable cutoff scores for AUDIT
      were higher among the psychotic than nonpsychotic patients, with 12 versus 10 in
      men and 8 versus 5 in women. The suitable cutoff scores for DUDIT were 1 in both
      psychotic and nonpsychotic women, and 5 versus 1 in psychotic and nonpsychotic
      men, respectively. This study shows that AUDIT and DUDIT may provide precise
      information about emergency psychiatric patients' problematic alcohol and drug
      use. 

PMID- 23548766
TI  - The role of transarterial embolization in the management of hematuria secondary
      to congenital renal arteriovenous malformations.
AB  - OBJECTIVE: To evaluate the efficacy and safety of transarterial embolization
      (TAE) in the management of hematuria secondary to congenital renal arteriovenous
      malformations (AVM). PATIENTS AND METHODS: Between May 2007 and February 2012, 6
      patients with congenital AVM treated with TAE were analyzed retrospectively,
      followed by a brief review of TAE in the treatment of congenital AVM. Clinical
      records with respect to general conditions, location, embolic materials,
      complications and overall outcome were collected from the original hospital
      charts and outpatient medical records. RESULTS: Three patients with AVM were
      confirmed by contrast-enhanced CT scans, and the other 3 patients were detected
      by renal angiography. TAE was performed with steel coils in 2 patients and n
      butyl-2-cyanoacrylate (NBCA) in 4 patients. After a mean follow-up of 22 months,
      no serious adverse effects were observed in all patients. There were no
      complaints of hematuria at the end of the follow-up period. CONCLUSION: For
      unexplained massive hematuria, congenital renal AVM needs to be considered as a
      differential diagnosis. Selective renal angiography and embolization should be
      recommended as the first choice to treat massive hematuria secondary to
      congenital renal AVM.

PMID- 23548767
TI  - Synthesis of nanowires via helium and neon focused ion beam induced deposition
      with the gas field ion microscope.
AB  - The ion beam induced nanoscale synthesis of platinum nanowires using the
      trimethyl (methylcyclopentadienyl)platinum(IV) (MeCpPt(IV)Me3) precursor is
      investigated using helium and neon ion beams in the gas field ion microscope. The
      He(+) beam induced deposition resembles material deposited by electron beam
      induced deposition with very small platinum nanocrystallites suspended in a
      carbonaceous matrix. The He(+) deposited material composition was estimated to be
      16% Pt in a matrix of amorphous carbon with a large room-temperature resistivity
      (~3.5 * 10(4)-2.2 * 10(5) MUOmega cm) and temperature-dependent transport
      behavior consistent with a granular material in the weak intergrain tunnel
      coupling regime. The Ne(+) deposited material has comparable composition (17%),
      however a much lower room-temperature resistivity (~600-3.0 * 10(3) MUOmega cm)
      and temperature-dependent electrical behavior representative of strong intergrain
      coupling. The Ne(+) deposited nanostructure has larger platinum nanoparticles and
      is rationalized via Monte Carlo ion-solid simulations which show that the neon
      energy density deposited during growth is much larger due to the smaller ion
      range and is dominated by nuclear stopping relative to helium which has a larger
      range and is dominated by electronic stopping.

PMID- 23548769
TI  - Controversies of the hormonal conservative treatment of endometrial cancer.
AB  - BACKGROUND: Hysterectomy plus salpingo-oophorectomy represents the standard
      treatment for patients with well-differentiated endometrial cancer (EC) limited
      to the endometrium. It is estimated that over 5% of EC are diagnosed in
      nulliparous women aged 35-44 years. In addition, EC can affect obese women with
      diabetes, hypertension and other comorbidities increasing the surgical risk.
      METHODS: This article reviews the English literature in PubMed regarding hormonal
      treatment of EC. RESULTS: Use of hormonal therapies has resulted in complete
      remission in 60-70%; many of these women were able to achieve full-term
      pregnancies, and in case of contraindication to surgery, resection could be
      avoided. Several topics, however, such as patient selection, interobserver
      histologic evaluation, the type/duration of hormonal treatment, modality of
      evaluation before treatment and surveillance after treatment, which are still
      subject to controversy, are therefore discussed in this paper. CONCLUSION: Uterus
      sparing treatment of well-differentiated EC limited to the endometrium is
      feasible and has acceptable efficacy in women with increased surgical risk or
      those who wish to preserve their fertility. Although the methods applied to
      determine disease extent beyond the endometrium are still unsatisfactory, patient
      selection is a crucial factor determining the outcome of treatment. However,
      women must be fully informed about the possibility of treatment failure and the
      necessity of a close follow-up after therapy.

PMID- 23548768
TI  - Magnetic resonance imaging-based versus computed tomography-based thrombolysis in
      acute ischemic stroke: comparison of safety and efficacy within a cohort study.
AB  - BACKGROUND: In acute ischemic stroke, brain imaging is mandatory in the decision
      whether to perform intravenous thrombolysis with recombinant tissue plasminogen
      activator. The most widespread used imaging modality to exclude intracranial
      hemorrhage is plain computed tomography (CT). However, there is an ongoing debate
      whether the information provided by magnetic resonance imaging (MRI) could
      improve the selection of patients for thrombolysis. We investigated whether the
      choice of imaging modality (MRI vs. CT) affects therapy safety and the patients'
      outcome. METHODS: Analyses are based on data from a prospective, single-center
      observational study that included all patients with acute ischemic stroke who
      received intravenous thrombolysis within 4.5 h. Stroke severity was assessed by
      the National Institutes of Health Stroke Scale. Safety was assessed by rates of
      symptomatic intracranial hemorrhage (SICH), brain edema with mass effect and 7
      day mortality. Outcome was assessed at 3 months as mortality and proportion of
      independent patients (modified Rankin Scale score between 0 and 2). RESULTS: We
      analyzed 345 patients of whom 141 received multimodal MRI and 204 received plain
      CT prior to treatment. Groups did not differ significantly in terms of age,
      neurological deficit, rate of elevated glucose level or rate of very high blood
      pressure. However, patients with CT-based thrombolysis had significantly higher
      rates of cardiac comorbidities (coronary artery disease, heart failure). In the
      MRI group, we observed a lower rate of 7-day mortality (1 vs. 10%; p = 0.001), a
      lower rate of SICH (1 vs. 6%; p = 0.010) and a nonsignificantly lower rate of
      brain edema with mass effect (2 vs. 6%; n.s.). In multivariable analysis, 7-day
      mortality was independently associated with MRI-based thrombolysis, even if
      cardiac comorbidities were taken into account. For mortality at 3 months, there
      was a nonsignificant difference in favor of the MRI group (16 vs. 23%; n.s.). In
      multivariable analyses, mortality at 3 months was independently associated with
      older age, higher stroke severity, brain edema with mass effect, SICH, pneumonia
      and coronary artery disease. Neither mortality nor independent outcome was
      influenced by initial imaging modality. CONCLUSIONS: Thrombolysis based on
      multimodal MRI is associated with reduced rates of SICH and early death. Our
      results suggest that these complications affect survival principally in the acute
      phase after thrombolysis. However, nonneurological and especially cardiac
      comorbidities also influence survival after stroke and are underrepresented in
      stroke patients undergoing MRI. Selection bias has to be considered.

PMID- 23548770
TI  - Fetal heart disease: severity, associated anomalies and parental decision.
AB  - OBJECTIVE: This study describes the association between the complexity of
      congenital cardiac and extracardiac malformations, and the parental decision of
      pregnancy continuation or termination. METHODS: Congenital heart defects (CHD)
      was diagnosed by ultrasound in 251 fetuses before the 24th week (23 + 6 weeks) of
      gestation during the four year period from 2007 to 2010. All fetuses from the
      Utrecht region were referred to our center due to a strict referral pattern. The
      complexity and severity of the cardiac and possible extracardiac malformations
      were retrospectively categorized by a pediatric cardiologist and a perinatologist
      who were blinded to the pregnancy outcome. The groups with and without
      termination of pregnancy were compared using a univariate analysis and
      multivariate logistic regression. RESULTS: In 119 (47%) of the 251 fetuses,
      parents opted for termination of pregnancy. In 103 of these cases (87%) there was
      a high complex or lethal cardiac, or a major or lethal extracardiac malformation.
      Of the 132 continued pregnancies, 42 fetuses (32%) had a high complex or lethal
      cardiac, or a major or lethal extracardiac malformation. There were significantly
      more terminations of pregnancy in case of a high or lethal complex cardiac or
      extracardiac anomaly (71 vs. 15%, p <0.001). CONCLUSION: Parents opted for
      termination of pregnancy significantly more often in cases with high complex
      cardiac and extracardiac malformations. It was rare for parents to opt for
      pregnancy termination in the absence of a severe cardiac or extracardiac
      malformation.

PMID- 23548771
TI  - The weight of obesity on lung health.

PMID- 23548772
TI  - GNAS -Related Loss-of-Function Disorders and the Role of Imprinting.
AB  - GNAS (guanine nucleotide-binding protein, alpha stimulating) is a complex
      imprinted locus coding, besides the alpha-stimulatory subunit of the G protein,
      the paternally (extra-large, antisense and A/B) and maternally (neuroendocrine
      secretory protein) transcripts. Heterozygous mutations in the coding sequence of
      GNAS produce dominant phenotypes (combination of resistances to hormones
      signaling through G-protein-coupled receptors, osteodystrophy and obesity) that
      depend on the parental origin of the mutated allele. Likewise, alterations in the
      methylation at promoters of GNAS transcripts, associated or not with deletions of
      imprinting control regions in the nearby STX16 gene or within GNAS, prompt
      resistance to parathormone when affecting the maternal allele. Therefore,
      imprinting of GNAS is the determining factor for the variability of the
      phenotype. Knowledge of the various phenotypes is necessary for genetic
      counseling as well as an appropriate therapeutic balance between regular follow
      up, prevention of disease complications and iatrogeny. 

PMID- 23548773
TI  - The changes of serum angiotensin-converting enzyme 2 in patients with pulmonary
      arterial hypertension due to congenital heart disease.
AB  - BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a primary component of the
      vasoprotective axis in the renin-angiotensin system (RAS), has recently been
      found to have regulatory actions in hypoxic pulmonary hypertension and
      monocrotaline-induced pulmonary hypertension. We explored the hypothesis that the
      level of ACE2 protein contents may be decreased in patients with pulmonary
      arterial hypertension (PAH) due to congenital heart disease (CHD). OBJECTIVE: We
      observed the serum ACE2 protein contents in patients with PAH due to CHD (CHD
      PAH), and investigated their correlation with mean pulmonary arterial pressure
      (mPAP). METHODS: One hundred and four patients with CHD and 33 normal control
      patients (group A) were involved in the research. The patients with CHD were
      divided into 55 cases of nonpulmonary hypertension (group B), 25 cases of mild to
      moderate pulmonary hypertension (group C) and 24 cases of severe pulmonary
      hypertension (group D). The serum level of ACE2 protein contents were detected by
      enzyme-linked immunosorbent assay (ELISA), and the relationship between these
      contents and mPAP were analyzed. RESULTS: ACE2 protein contents significantly
      declined as mPAP increased. The mPAP was negatively correlated with the level of
      ACE2 protein contents. CONCLUSIONS: These results demonstrated that ACE2 may play
      an important regulatory role in CHD-PAH.

PMID- 23548774
TI  - Genetic variation in MAOA modulates prefrontal cortical regulation of approach
      avoidance reactions.
AB  - BACKGROUND: Regulation of automatic approach and avoidance behavior requires
      affective and cognitive control, which are both influenced by a genetic variation
      in the gene encoding Monoamine Oxidase A (termed MAOA-uVNTR). METHODS: The
      current study investigated MAOA genotype as a moderator of prefrontal cortical
      activation measured with functional near-infrared spectroscopy (fNIRS) in 37
      healthy young adults during performance of the approach-avoidance task with
      positive and negative pictures. RESULTS: Carriers of the low- compared to the
      high-expressing genetic variant (MAOA-L vs. MAOA-H) showed increasing regulatory
      activity in the right dorsolateral prefrontal cortex (DLPFC) during incompatible
      conditions (approach negative, avoid positive). This might have been a
      compensatory mechanism for stronger emotional reactions as shown in previous
      studies and might have prevented any influence of incompatibility on behavior. In
      contrast, fewer errors but also lower activity in the right DLPFC during
      processing of negative compared to positive stimuli indicated MAOA-H carriers to
      have used other regulatory areas. This resulted in slower reaction times in
      incompatible conditions, but--in line with the known better cognitive regulation
      efficiency--allowed them to perform incompatible reactions without activating the
      DLPFC as the highest control instance. Carriers of one low- and one high
      expressing allele lay as an intermediate group between the reactions of the low-
      and high-expressing groups. CONCLUSIONS: The relatively small sample size and
      restriction to fNIRS for assessment of cortical activity limit our findings.
      Nevertheless, these first results suggest monoam-inergic mechanisms to contribute
      to interindividual differences in the two basic behavioral principles of approach
      and avoidance and their neuronal correlates.

PMID- 23548775
TI  - When blood meets nitrogen oxides: pregnancy complications and air pollution
      exposure.

PMID- 23548776
TI  - Optimal methods for using posterior probabilities in association testing.
AB  - OBJECTIVE: The use of haplotypes to impute the genotypes of unmeasured single
      nucleotide variants continues to rise in popularity. Simulation results suggest
      that the use of the dosage as a one-dimensional summary statistic of imputation
      posterior probabilities may be optimal both in terms of statistical power and
      computational efficiency; however, little theoretical understanding is available
      to explain and unify these simulation results. In our analysis, we provide a
      theoretical foundation for the use of the dosage as a one-dimensional summary
      statistic of genotype posterior probabilities from any technology. METHODS: We
      analytically evaluate the dosage, mode and the more general set of all one
      dimensional summary statistics of two-dimensional (three posterior probabilities
      that must sum to 1) genotype posterior probability vectors. RESULTS: We prove
      that the dosage is an optimal one-dimensional summary statistic under a typical
      linear disease model and is robust to violations of this model. Simulation
      results confirm our theoretical findings. CONCLUSIONS: Our analysis provides a
      strong theoretical basis for the use of the dosage as a one-dimensional summary
      statistic of genotype posterior probability vectors in related tests of genetic
      association across a wide variety of genetic disease models.

PMID- 23548777
TI  - Effects of everolimus on oxidative stress in kidney model of ischemia/reperfusion
      injury.
AB  - BACKGROUND/AIMS: Reactive oxygen species play an important role in the
      pathogenesis of kidney ischemia/reperfusion injury (IRI) which may be influenced
      by immunosuppressive therapy. Pertinent to this, we investigated the effects of
      the mTOR inhibitor everolimus on redox settings and the activity of the anti
      oxidative system in kidneys exposed to IRI. METHODS: C57BL/6 mice were subjected
      to IRI by clamping both renal pedicles for 45 min. Everolimus was applied in
      daily, subcutaneous doses (0.25 mg/kg body weight), starting 1 day before IRI
      induction. Both everolimus-treated and non-treated mice were sacrificed at
      several time points, starting 30 min and finishing 7 days after IRI induction.
      Markers of oxidation such as glutathione and NADPH levels and anti-oxidative
      enzyme activities were determined in the kidneys. RESULTS: In comparison to both
      sham and non-treated animals, the treatment with everolimus resulted in an
      increased level of markers of oxidation, including a lower level of glutathione,
      increased level of oxidized glutathione and reduced level of NADPH. The activity
      of superoxide dismutase was reduced in both experimental groups, but the effects
      were less pronounced in everolimus-treated animals. In the early phase of
      reperfusion, everolimus-treated animals showed higher activity of glutathione
      reductase in comparison to non-treated animals, whereas the activities of
      glutathione peroxidase and catalase were generally similar. The treatment with
      everolimus significantly reduced heme oxygenase-1 expression and increased iNOS
      mRNA expression when compared to non-treated animals. CONCLUSION: Our data imply
      that everolimus treatment may decrease cytoprotective capacity in kidneys exposed
      to IRI due to promoted oxidative/nitrosative stress.

PMID- 23548778
TI  - Using neurobiological measures to predict and assess treatment outcome of
      psychotherapy in posttraumatic stress disorder: systematic review.
AB  - BACKGROUND: Trauma-focused cognitive-behavioral therapy (TF-CBT) and eye movement
      desensitization and reprocessing (EMDR) are effective treatments for
      posttraumatic stress disorder. However, little is known about their
      neurobiological effects. The usefulness of neurobiological measures to predict
      the treatment outcome of psychotherapy also has yet to be determined. METHODS:
      Systematic review of randomized controlled trials (RCTs) focused on
      neurobiological treatment effects of TF-CBT or EMDR and trials with
      neurobiological measures as predictors of treatment response. RESULTS: We
      included 23 publications reporting on 16 separate trials. TF-CBT was compared
      with a waitlist in most trials. TF-CBT was associated with a decrease in heart
      rate and blood pressure and changes in activity but not in volume of frontal
      brain structures and the amygdala. Neurobiological changes correlated with
      changes in symptom severity. EMDR was only tested against other active treatments
      in included trials. We did not find a difference in neurobiological treatment
      effects between EMDR and other treatments. Publications on neurobiological
      predictors of treatment response showed ambiguous results. CONCLUSION: TF-CBT was
      associated with a reduction of physiological reactivity. There is some
      preliminary evidence that TF-CBT influences brain regions involved in fear
      conditioning, extinction learning and possibly working memory and attention
      regulation; however, these effects could be nonspecific psychotherapeutic
      effects. Future trials should use paradigms aimed specifically at these brain
      regions and physiological reactivity. There are concerns regarding the risk of
      bias in some of the RCTs, indicating that methodologically more rigorous trials
      are required. Trials with neurobiological measures as predictors of treatment
      outcome render insufficient results to be useful in clinical practice.

PMID- 23548779
TI  - Role of matrix metalloproteinase-2 in recovery after tubular damage in acute
      kidney injury in mice.
AB  - BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are zinc endopeptidases that
      degrade extracellular matrix and are involved in the pathogenesis of ischemic
      damage in acute kidney injury (AKI). In the present study, we analyzed the role
      of MMP-2 in the repair process in ischemic AKI. METHODS: AKI was induced in MMP-2
      wild-type (MMP-2(+/+)) and MMP-2-deficient (MMP-2(-/-)) mice by 90-min renal
      artery clamping followed by reperfusion. Renal histology and the activity and
      distribution of MMP-2 were examined from day 1 to day 14. During the recovery
      from AKI, MMP-2(+/+) mice were also treated with MMP-2/MMP-9 inhibitor. RESULTS:
      In both MMP-2(+/+) and MMP-2(-/-) mice, AKI developed on day 1 after
      ischemia/reperfusion with widespread acute tubular injury, but subsequent
      epithelial cell proliferation was evident on days 3-7. During the repair process,
      active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP
      2(+/+) mice on days 7-14, and the tubular repair process was almost complete by
      day 14. On the other hand, in MMP-2(-/-) mice, less prominent proliferation of
      tubular epithelial cells was evident on days 3 and 7, and damaged tubules that
      were covered with elongated and immature regenerated epithelial cells were
      identified on days 7 and 14. Incomplete recovery of injured microvasculature was
      also noted with persistent macrophage infiltration. Similarly, treatment with MMP
      2/MMP-9 inhibitor resulted in impaired recovery in MMP-2(+/+) mice. CONCLUSION:
      MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9
      inhibitor was a disadvantage when it was administered during the repair stage of
      ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to
      enhance recovery from AKI.

PMID- 23548782
TI  - High efficiency photoelectrochemical water splitting and hydrogen generation
      using GaN nanowire photoelectrode.
AB  - We have studied the photoelectrochemical properties of both undoped and Si-doped
      GaN nanowire arrays in 1 mol l(-1) solutions of hydrogen bromide and potassium
      bromide, which were used separately as electrolytes. It is observed that
      variations of the photocurrent with bias voltage depend strongly on the n-type
      doping in GaN nanowires in both electrolytes, which are analyzed in the context
      of GaN surface band bending and its variation with the incorporation of Si
      doping. Maximum incident-photon-to-current-conversion efficiencies of ~15% and
      18% are measured for undoped and Si-doped GaN nanowires under ~350 nm light
      illumination, respectively. Stable hydrogen generation is also observed at a zero
      bias potential versus the counter-electrode.

PMID- 23548780
TI  - Rice cytokinin GATA transcription Factor1 regulates chloroplast development and
      plant architecture.
AB  - Chloroplast biogenesis has been well documented in higher plants, yet the complex
      methods used to regulate chloroplast activity under fluctuating environmental
      conditions are not well understood. In rice (Oryza sativa), the CYTOKININ
      RESPONSIVE GATA TRANSCRIPTION FACTOR1 (Cga1) shows increased expression following
      light, nitrogen, and cytokinin treatments, while darkness and gibberellin reduce
      expression. Strong overexpression of Cga1 produces dark green, semidwarf plants
      with reduced tillering, whereas RNA interference knockdown results in reduced
      chlorophyll and increased tillering. Coexpression, microarray, and real-time
      expression analyses demonstrate a correlation between Cga1 expression and the
      expression of important nucleus-encoded, chloroplast-localized genes.
      Constitutive Cga1 overexpression increases both chloroplast biogenesis and starch
      production but also results in delayed senescence and reduced grain filling.
      Growing the transgenic lines under different nitrogen regimes indicates potential
      agricultural applications for Cga1, including manipulation of biomass,
      chlorophyll/chloroplast content, and harvest index. These results indicate a
      conserved mechanism by which Cga1 regulates chloroplast development in higher
      plants.

PMID- 23548781
TI  - Modified Clp protease complex in the ClpP3 null mutant and consequences for
      chloroplast development and function in Arabidopsis.
AB  - The plastid ClpPRT protease consists of two heptameric rings of
      ClpP1/ClpR1/ClpR2/ClpR3/ClpR4 (the R-ring) and ClpP3/ClpP4/ClpP5/ClpP6 (the P
      ring) and peripherally associated ClpT1/ClpT2 subunits. Here, we address the
      contributions of ClpP3 and ClpP4 to ClpPRT core organization and function in
      Arabidopsis (Arabidopsis thaliana). ClpP4 is strictly required for embryogenesis,
      similar to ClpP5. In contrast, loss of ClpP3 (clpp3-1) leads to arrest at the
      hypocotyl stage; this developmental arrest can be removed by supplementation with
      sucrose or glucose. Heterotrophically grown clpp3-1 can be transferred to soil
      and generate viable seed, which is surprising, since we previously showed that
      CLPR2 and CLPR4 null alleles are always sterile and die on soil. Based on native
      gels and mass spectrometry-based quantification, we show that despite the loss of
      ClpP3, modified ClpPR core(s) could be formed, albeit at strongly reduced levels.
      A large portion of ClpPR subunits accumulated in heptameric rings, with
      overaccumulation of ClpP1/ClpP5/ClpP6 and ClpR3. Remarkably, the association of
      ClpT1 to the modified Clp core was unchanged. Large-scale quantitative proteomics
      assays of clpp3-1 showed a 50% loss of photosynthetic capacity and the up
      regulation of plastoglobules and all chloroplast stromal chaperone systems.
      Specific chloroplast proteases were significantly up-regulated, whereas the major
      thylakoid protease (FtsH1/FtsH2/FtsH5/FtsH8) was clearly unchanged, indicating a
      controlled protease network response. clpp3-1 showed a systematic decrease of
      chloroplast-encoded proteins that are part of the photosynthetic apparatus but
      not of chloroplast-encoded proteins with other functions. Candidate substrates
      and an explanation for the differential phenotypes between the CLPP3, CLPP4, and
      CLPP5 null mutants are discussed.

PMID- 23548783
TI  - Influence of body mass index, surgical approach and lymphadenectomy on the
      development of symptomatic lymphoceles after radical prostatectomy.
AB  - PURPOSE: Identification of factors influencing lymphocele formation requiring
      intervention after radical prostatectomy. METHODS: 302 patients undergoing
      radical retropubic prostatectomy (RRP, n = 174) or transperitoneal robot-assisted
      laparoscopic prostatectomy (RALP, n = 128) by the same surgeon were
      retrospectively reviewed. Incidence of symptomatic lymphoceles (SLC) was compared
      with clinical and pathological data (contingency analyses, Wilcoxon-Kruskal
      Wallis test). RESULTS: Sixteen patients (5.3%) developed SLC. SLC occurred
      significantly more frequently after RRP compared to RALP (8.0 vs. 0.8%, p =
      0.0008). Patients with SLC had more lymph nodes (LN) removed median (17 vs. 13, p
      = 0.009) and a significantly lower BMI (median 24.4 vs. 26.4, p = 0.0008).
      Presence of LN metastases (n = 18 patients, 6.0%) showed no statistical impact on
      SLC. In a multivariate analysis surgical method, the number of resected LN and
      the BMI remained independent predictors of SLC formation. CONCLUSIONS: The lower
      incidence of SLC after RALP compared to RRP probably results from peritoneal
      drainage of lymphatic fluid. The correlation of removed LN and SLC might be
      explained by increased injury of lymphatic vessels during more extended LN
      dissection. Why patients with lower BMI are more prone to develop SLC still
      remains unclear. However, early postoperative mobilization in nonobese patients
      might be a contributing factor.

PMID- 23548784
TI  - The concepts of rash impulsiveness and reward sensitivity in substance use
      disorders.
AB  - According to recent theories of addiction, the commonly used term impulsivity
      comprises two factors: rash impulsiveness and reward sensitivity. The present
      study addresses the relevance and generalizability of this two-factor model in a
      clinical sample of substance use disorder patients. This was examined by
      examining both internal and external validity. In addition, a comparison was made
      between self-reported and behavioral measures reflecting reward sensitivity and
      rash impulsiveness. Results provide evidence for the existence of the two
      hypothesized impulsivity factors in a clinical sample of substance dependent
      patients. Meaningful relationships between the model and drug use characteristics
      have been found, providing further evidence for the validity of the two-factor
      model. Furthermore, it is suggested that behavioral and self-report measures of
      impulsivity represent different constructs. 

PMID- 23548785
TI  - Effect of caffeic acid phenethyl ester on intra-abdominal adhesion in rats.
AB  - BACKGROUND: To determine the impact of caffeic acid phenethyl ester (CAPE) on
      abdominal adhesion formation after laparotomy. METHODS: Forty female rats were
      allocated into four distinct groups on which laparotomy alone; laparotomy with
      traumatization of the uterine horns; laparotomy, traumatization of the uterine
      horns and intraperitoneal irrigation with saline, and laparotomy, traumatization
      of the uterine horns and intraperitoneal irrigation with CAPE were performed.
      After sacrifying the animals on the 14th postoperative day, histopathological
      examination and biochemical analysis were conducted to evaluate the formation of
      abdominal adhesions and antioxidant status. RESULTS: In the CAPE group, total
      adhesion scores were significantly lower than in the control and saline groups.
      The CAPE group displayed less inflammation, giant cell formation, fibrosis and
      fibroblastic activity than the control group. On the other hand, the control
      group displayed higher total adhesion scores. CONCLUSION: The results of this
      study indicate that the administration of CAPE may have beneficial effects for
      the prevention of abdominal adhesion formation after laparotomy. Further clinical
      studies are mandatory to explore the actual therapeutic potential of CAPE.

PMID- 23548786
TI  - Alterations in eicosanoid levels during U937 bcl-xL tumour growth suppression and
      recovery in NU/NU mice in vivo-Involvement of phospholipase A2.
AB  - We report the effects of two anti-cancer drugs, PBT-4, an experimental antagonist
      to the pro-inflammatory hepoxilins, and Gleevec (STI-571), an anti-leukaemic
      drug, on eicosanoid tumour levels in immunodeficient mice (NU/NU) xenografted
      with the leukaemic cell line, U937 bcl-xL. After the tumours had grown to 80
      100mm(3) volume, an 8-day treatment with the drugs was initiated and the animals
      were monitored for 28 days. On various days, tumours were removed for measurement
      of 24 omega-6 eicosanoids. The data show remarkable direct correlation between
      inhibition of tumour AA release and 12-LOX products (including 12-HETE and
      hepoxilins) during PBT or STI treatment with tumour growth suppression. These
      findings suggest that inhibition of AA release may represent a novel underlying
      mechanism of action of PBT-4 (and STI) in vivo in suppressing tumour growth. As
      the PBT wears off, AA and 12-LOX products rise rapidly (Day 18) leading to the
      observed tumour growth spurt. 

PMID- 23548787
TI  - New media for health education: a revolution in progress.

PMID- 23548788
TI  - Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro
      inflammatory cytokine inhibition.
AB  - BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease.
      Recently, the use of anti-TNF-alpha in treating resistant forms of PRP has been
      reported. OBJECTIVES: To evaluate the clinical efficacy of infliximab in the
      treatment of PRP along with the evolution of secretion of some serum cytokines
      during treatment. METHODS: Patients presenting widespread PRP were included
      consecutively and treated with infliximab. We compared cytokine profiles (notably
      CXCL-10 and TNF-alpha) by ELISA in sera from both patients with PRP and controls
      (healthy/psoriasis) at the time of diagnosis and after clinical remission (PRP).
      RESULTS: 4 patients were treated with infliximab and achieved complete remission
      without any recurrence after treatment ending. The serum level of TNF-alpha and
      CXCL-10 was increased at the time of inclusion and normalized after treatment.
      Analysis of the typical component of the T helper cell 1 (Th1) and Th2 cytokine
      network did not show modification. CONCLUSION: Infliximab is an effective
      treatment of PRP. The analysis of the cytokine profile is in agreement with an
      absence of further recurrence of PRP by an early and unique inflammatory
      mechanism without significant underlying autoimmunity.

PMID- 23548789
TI  - Does stroke subtype and measurement technique influence estimation of cerebral
      autoregulation in acute ischaemic stroke?
AB  - BACKGROUND: It is known that dynamic cerebral autoregulation (dCA) is acutely
      impaired following ischaemic stroke (IS). However, the influence of stroke
      subtype, the affected (AF) and unaffected (UA) hemispheres, and the effects of a
      methodological approach on dCA estimates in stroke are all inconclusive.
      Therefore, we studied cortical and subcortical acute IS (AIS) patients to test
      the primary hypotheses that (1) dCA is impaired in stroke subtypes when compared
      to controls, (2) dCA impairment is more pronounced in the AF compared with the UA
      hemisphere, and (3) similar results are obtained with both spontaneous blood
      pressure (BP) fluctuation techniques, and sudden induced BP changes by thigh cuff
      deflation. METHODS: We assessed the dCA values in AIS patients and in healthy
      controls (n = 10). The AIS patient group consisted of anterior circulation
      cortical (n = 11) and subcortical (n = 11) strokes within 48 h of symptom onset.
      Cerebral blood flow velocity was measured using transcranial Doppler ultrasound,
      and BP measurements were recorded before, during and after the release of
      bilateral thigh cuffs in 10 controls (7 males) of a mean age of 59 +/-15 years
      (range 31-75), 11 cortical strokes (7 males) of a mean of age 65 +/- 19 years
      (range 25-88) and 11 subcortical strokes (7 males) of a mean age of 60 +/- 18
      years (range 39-85). Autoregulation index (ARI) estimates, calculated using
      spontaneous fluctuations and thigh cuff manoeuvre, were derived. Differences in
      ARI (Tiecks' model) were tested with repeated-measures ANOVA. RESULTS: A total of
      22 patients were included, comprising 11 subcortical (lacunar clinical syndrome)
      and 11 cortical strokes (total anterior circulation stroke/partial anterior
      circulation syndrome). Of the 10 control subjects, 1 later withdrew because of
      intolerance to the thigh cuffs. Similar ARI estimates were obtained in both
      groups, whether assessed from spontaneous fluctuations or thigh cuff measurements
      (p = 0.37). ARI differences were not significantly different between hemispheres
      for both control and stroke populations. ARI was significantly impaired in AIS
      patients compared to age-, sex- and BP-matched control subjects, with a greater
      impairment of dCA observed in cortical IS. CONCLUSIONS: The results of this study
      suggest that both spontaneous fluctuations and thigh cuff deflation techniques
      are able to provide reliable estimates of ARI, with the estimates from both
      spontaneous fluctuations and thigh cuff deflation techniques being in keeping
      with those reported elsewhere in the literature. dCA was impaired following AIS
      compared to controls when stroke subtype was considered. Importantly, no
      differences were observed between UA and AF. This has implications for the
      assessment of CA after stroke and reinforces the need to define a 'gold standard'
      test for the investigation of CA.

PMID- 23548790
TI  - The dark side of implantable cardioverter defibrillator therapy.

PMID- 23548791
TI  - Height gain at adult-height age in 184 short patients treated with growth hormone
      from prepubertal age to near adult-height age is not related to GH secretory
      status at GH therapy onset.
AB  - BACKGROUND: GH release after stimuli classifies short children as severe
      idiopathic isolated GH deficiency (IIGHD), mild IIGHD, dissociated GH release
      (DGHR) and normal GH release (NGHR) and anthropometric birth data as adequate for
      gestational age (AGA) or small for gestational age (SGA). GH release after
      stimuli classifies AGA patients as IIGHD or as idiopathic short stature (ISS).
      AIM: To compare height gain induced by GH therapy (31.8 +/- 3.5 ug/kg/day, 7.7 +/
      1.6 years) started at prepubertal age and stopped at near adult-height age.
      METHODS: A retrospective longitudinal multicenter study including 184 short
      patients classified as severe IIGHD n = 25, mild IIGHD n = 75, DGHR n = 55 and
      NGHR n = 29; or as IIGHD n = 78, ISS n = 57 and SGA n = 49. Height gain was
      evaluated throughout GH therapy and at adult-height age. RESULTS: Height-SDS gain
      at adult-height age was similar among severe IIGHD (1.8 +/- 0.8 SDS), mild IIGHD
      (1.6 +/- 0.6 SDS), DGHR (1.7 +/- 0.7 SDS) and NGHR (1.6 +/- 0.7 SDS), or among
      IIGHD (1.7 +/- 0.7 SDS), ISS (1.7 +/- 0.6 SDS) and SGA (1.6 +/- 0.8 SD).
      CONCLUSION: GH-release stimuli are of little help for deciding on GH therapy in
      the clinical management of prepubertal children with IIGHD, ISS or SGA.

PMID- 23548792
TI  - Upregulation of intestinal NHE3 following saline ingestion.
AB  - BACKGROUND: Little is known about the effect of salt content of ingested fluid on
      intestinal transport processes. Osmosensitive genes include the serum- and
      glucocorticoid-inducible kinase SGK1, which is up-regulated by hyperosmolarity
      and cell shrinkage. SGK1 is in turn a powerful stimulator of the intestinal
      Na(+)/H(+) exchanger NHE3. The present study was thus performed to elucidate,
      whether the NaCl content of beverages influences NHE3 activity. METHODS: Mice
      were offered access to either plain water or isotonic saline ad libitum. NHE3
      transcript levels and protein abundance in intestinal tissue were determined by
      confocal immunofluorescent microscopy, RT-PCR and western blotting, cytosolic pH
      (pHi) in intestinal cells from 2',7'-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein (BCECF) fluorescence and Na(+)/H(+) exchanger activity from
      the Na(+) dependent realkalinization following an ammonium pulse. RESULTS: Saline
      drinking significantly enhanced fluid intake and increased NHE3 transcript
      levels, NHE3 protein and Na(+)/H(+) exchanger activity. CONCLUSIONS: Salt content
      of ingested fluid has a profound effect on intestinal Na(+)/H(+) exchanger
      expression and activity.

PMID- 23548793
TI  - A novel nuclear factor kappaB inhibitor, dehydroxymethylepoxyquinomicin,
      ameliorates puromycin aminonucleoside-induced nephrosis in mice.
AB  - BACKGROUND/AIMS: Minimal-change nephrotic syndrome (MCNS) is a kidney disease
      defined by selective proteinuria and hypoalbuminemia occurring in the absence of
      cellular glomerular infiltrates or immunoglobulin deposits. Recent observations
      suggest that nuclear factor kappaB (NF-kappaB) of podocyte is strongly associated
      with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin
      (DHMEQ) is a novel NF-kappaB inhibitor that potently inhibits DNA-binding
      activity of NF-kappaB, resulting in several therapeutic effects in various
      pathological conditions. We conducted this study to ask whether DHMEQ may
      ameliorate the nephrosis in mice induced by puromycin aminonucleoside (PAN),
      which is considered to be an animal model for MCNS. METHODS/RESULTS: Pretreatment
      with DHMEQ alleviated the proteinuria and reversed the serum abnormalities in
      mice nephrosis induced by 450 mg/kg of PAN. Increased serum interleukin-6 level
      in PAN-induced nephrosis was also completely suppressed by DHMEQ. Electron
      microscopic analyses of glo-meruli indicated that DHMEQ can inhibit the podocyte
      foot process effacement via blocking the translocation of podocyte NF-kappaB from
      cytoplasm to nucleus. CONCLUSIONS: These results suggest that DHMEQ can be a
      potential therapeutic agent for MCNS.

PMID- 23548794
TI  - EMDR therapy modulates the default mode network in a subsyndromal, traumatized
      bipolar patient.
AB  - BACKGROUND: Some functional imaging abnormalities found in bipolar disorder are
      state related, whereas others persist into euthymia. It is uncertain to what
      extent these latter changes may reflect continuing subsyndromal affective
      fluctuations and whether those can be modulated by therapeutic interventions.
      METHOD: We report functional magnetic resonance imaging (fMRI) findings during
      performance of the n-back working memory task in a bipolar patient who showed a
      marked improvement in subsyndromal affective symptoms after receiving eye
      movement desensitization and reprocessing (EMDR) therapy in the context of a
      clinical trial. RESULTS: The patient's clinical improvement was accompanied by
      marked changes in functional imaging, as compared to 30 healthy subjects. fMRI
      changes were noted particularly in deactivation, with failure of deactivation in
      the medial frontal cortex partially normalizing after treatment. CONCLUSIONS:
      This case supports the potential therapeutic overall benefit of EMDR in
      traumatized bipolar patients and suggests a possible neurobiological mechanism of
      action: normalization of default mode network dysfunction.

PMID- 23548795
TI  - Toward primary prevention of cancer: the case for a global strategy to limit
      avoidable exposures.

PMID- 23548796
TI  - Systematic review of blinding assessment in randomized controlled trials in
      schizophrenia and affective disorders 2000-2010.
AB  - BACKGROUND: Blinding is an integral part of many randomized controlled trials
      (RCTs). However, both blinding and blinding assessment seem to be rarely
      documented in trial reports. METHOD: Systematic review of articles on RCTs in
      schizophrenia and affective disorders research during 2000-2010. RESULTS: Among
      2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported
      assessing participant, rater, or clinician blinding: 5/672 reports on
      schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective
      disorders, without significant trends across the decade. Rarely was blinding
      assessed at the beginning, in most studies assessment was at the end. Proportion
      of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per
      study, with slightly more correct guesses in treatment arms than in placebo arms.
      Three fourths of responders correctly guessed that they received the active
      agent. Blinding assessment was more frequently reported in papers on
      psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs.
      8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was
      associated with: (a) positive findings, (b) full industrial sponsorship, and (c)
      diagnosis of schizophrenia. There was a moderate association of treatment success
      and blinding status of both trial participants (r = 0.51, p = 0.002) and raters
      (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding
      documentation of persons blinded (60%) or of efforts to match interventions
      (50%). CONCLUSIONS: Recent treatment trials in major psychiatric disorders rarely
      reported on or evaluated blinding. We recommend routine documentation of blinding
      strategies in reports.

PMID- 23548799
TI  - Evaluation of surgical outcome of penile augmentation and lengthening procedures.
AB  - Our study included 280 patients complaining of small-sized penis. They were seen
      in the outpatient clinic of the Andrology Department, Kasr El Aini, Cairo
      University. Patients were collected from 2002 till 2008 and classified into 4
      categories from an etiological point of view. Eleven patients (3.9%) were
      operated upon according to fine selection criteria; six patients were selected
      for lengthening procedures, while two patients were selected for increasing girth
      procedures and three patients for combined operation of lengthening and
      increasing girth techniques. Seven patients showed subjective satisfaction after
      lengthening procedures and four patients showed subjective satisfaction after
      increasing girth techniques. In conclusion, detailed analysis of short penis
      complaint with a proper diagnosis and patient education are required for accurate
      management of patients complaining of a short penis.

PMID- 23548798
TI  - Impaired error-monitoring function in people with Internet addiction disorder: an
      event-related fMRI study.
AB  - BACKGROUND: Internet addiction disorder (IAD) is rapidly becoming a prevalent
      mental health concern around the world. The neurobiological underpinnings of IAD
      should be studied to unravel the potential heterogeneity. This study was set to
      investigate the error-monitoring ability in IAD subjects. METHODS: Fifteen IAD
      subjects and 15 healthy controls (HC) participated in this study. Participants
      were asked to perform a fast Stroop task that may show error responses.
      Behavioral and neurobiological results in relation to error responses were
      compared between IAD subjects and HC. RESULTS: Compared to HC, IAD subjects
      showed increased activation in the anterior cingulate cortex (ACC) and decreased
      activation in the orbitofrontal cortex following error responses. Significant
      correlation was found between ACC activation and the Internet addiction test
      scores. CONCLUSIONS: IAD subjects show an impaired error-monitoring ability
      compared to HC, which can be detected by the hyperactivation in ACC in error
      responses.

PMID- 23548797
TI  - Efficient simulation of epistatic interactions in case-parent trios.
AB  - Statistical approaches to evaluate interactions between single nucleotide
      polymorphisms (SNPs) and SNP-environment interactions are of great importance in
      genetic association studies, as susceptibility to complex disease might be
      related to the interaction of multiple SNPs and/or environmental factors. With
      these methods under active development, algorithms to simulate genomic data sets
      are needed to ensure proper type I error control of newly proposed methods and to
      compare power with existing methods. In this paper we propose an efficient method
      for a haplotype-based simulation of case-parent trios when the disease risk is
      thought to depend on possibly higher-order epistatic interactions or gene
      environment interactions with binary exposures.

PMID- 23548800
TI  - Vitamin D receptor activators upregulate and rescue podocalyxin expression in
      high glucose-treated human podocytes.
AB  - BACKGROUND: Vitamin D is beneficial in human and experimental chronic kidney
      disease, the leading cause of which is diabetic nephropathy. Vitamin D through
      its receptor, VDR, provides renal protection in diabetic nephropathy, but limited
      data exist about its effect on podocytes. Renal podocytes form the main
      filtration barrier possessing a unique phenotype maintained by proteins including
      podocalyxin and nephrin, the expression of which is suppressed in pathological
      conditions. METHODS: We used immortalized human podocytes (human glomerular
      epithelial cells, HGEC) to assess podocalyxin and nephrin expression after
      treatment with 1,25-dihydroxyvitamin D3 (calcitriol) and its analogue
      paricalcitol. The involvement of VDR was investigated by silencing with hVDR
      siRNA and ChIP analysis. RESULTS: HGEC exhibit high glucose-mediated
      downregulation of podocalyxin and nephrin, loss of which has been linked with
      loss of the permselective renal barrier and proteinuria. Calcitriol and
      paricalcitol reversed high glucose-induced decrease of nephrin and significantly
      enhanced podocalyxin expression in podocytes cultured in high glucose. HGEC
      express VDR and retinoid X receptor (RXR). In the presence of calcitriol and
      paricalcitol, VDR expression was upregulated and VDR colocalized with RXR in the
      nucleus. VDR knockdown abolished the protective action of calcitriol and
      paricalcitol on podocalyxin expression indicating that podocalyxin activation of
      expression is partly mediated by VDR. Furthermore, VDR specifically regulates
      podocalyxin expression by bounding to a site upstream of the podocalyxin
      promoter. CONCLUSION: Vitamin D analogues maintain and, furthermore, re-activate
      the expression of specialized components of podocytes including podocalyxin,
      hence they provide protection against loss of the permselective renal barrier,
      with molecular mechanisms elucidated herein.

PMID- 23548802
TI  - Laparoscopic adnexectomy with peritonectomy for an ovarian tumor adhered to the
      pelvic sidewall.
AB  - Laparoscopic adnexectomy is one of the most commonly used surgical techniques for
      the treatment of ovarian tumor. However, many physicians find it difficult to
      conduct the resection without rupturing the ovarian tumor, especially in cases
      with tumor adhesions. In the case we are presenting, we unexpectedly encountered
      an ovarian tumor adherent to the pelvic sidewall. Because the possibility of a
      malignancy could not be completely excluded, we decided to concomitantly resect
      the ovary and its adherent peritoneum, to avoid any potential tumor rupture due
      to its manipulation. We were successfully able to laparoscopically retrieve the
      intact ovarian tumor, without its rupture. The pathological diagnosis was of a
      Grade 2, FIGO stage IIb endometrioid adenocarcinoma of both ovaries. As a result
      of this diagnosis, we performed a comprehensive staging laparoscopy. Following
      the completion of adjuvant chemotherapy, the patient has showed no signs of
      recurrent malignancy after 3 years. This case report describes our technique for
      the surgical management of an ovarian tumor adherent to the pelvic wall. To avoid
      spillage of the tumor contents, the simultaneous resection of the tumor with its
      adhered peritoneum is a useful method to consider.

PMID- 23548801
TI  - Alternative low-cost approach to the synthesis of magnetic iron oxide
      nanoparticles by thermal decomposition of organic precursors.
AB  - A new approach to thermal decomposition of organic iron precursors is reported,
      which results in a simpler and more economical method to produce well
      crystallized gamma-Fe2O3 nanoparticles (NPs) with average sizes within the 3-17
      nm range. The NPs were characterized by TEM, SAED, XRD, DLS-QELS, Mossbauer
      spectroscopy at different temperatures, FT-IR and magnetic measurements. The
      obtained gamma-Fe2O3 NPs are coated with oleic acid and, in a lower quantity,
      with oleylamine (about 1.5 nm in thickness). It was shown that changing operative
      variables allows us to tune the average particle diameters and obtain a very
      narrow or monodisperse distribution of sizes. The gamma-Fe2O3 NPs behave
      superparamagnetically at room temperature and their magnetization saturation is
      reduced by about 34% in comparison with bulk maghemite. The results indicate that
      the distance between two neighbour NPs, generated by the coating, of about 3 nm
      is insufficient to inhibit interparticle magnetic interactions when the average
      diameter is 8.8 nm. The good quality of the NPs, obtained through the present low
      cost and easy-handling process, open a new perspective for future technological
      applications.

PMID- 23548803
TI  - Systematic phylogenetic analysis of influenza A virus reveals many novel mosaic
      genome segments.
AB  - Recombination plays an important role in shaping the genetic diversity of a
      number of DNA and RNA viruses. Although some recent studies have reported
      bioinformatic evidence of mosaic sequences in a variety of influenza A viruses,
      it remains controversial as to whether these represent bona fide natural
      recombination events or laboratory artifacts. Importantly, mosaic genome
      structures can create significant topological incongruence during phylogenetic
      analyses, which can mislead additional phylogeny-based molecular evolutionary
      analyses such as molecular clock dating, the detection of selection pressures and
      phylogeographic inference. As a result, there is a strong need for systematic
      screenings for mosaic structures within the influenza virus genome database. We
      used a combination of sequence-based and phylogeny-based methods to identify 388
      mosaic influenza genomic segments, of which 332 are previously unreported and are
      significantly supported by phylogenetic methods. It is impossible, however, to
      ascertain whether these represent natural recombinants. To facilitate the future
      identification of recombinants, reference sets of non-recombinant sequences were
      selected for use in an automatic screening protocol for detecting mosaic
      sequences. Tests using real and simulated mosaic sequences indicate that our
      screening protocol is both sensitive (average >90%) and accurate (average >77%)
      enough to identify a range of different mosaic patterns. The relatively high
      prevalence of mosaic influenza virus sequences implies that efficient systematic
      screens, such as that proposed here, should be performed routinely to detect
      natural recombinant strains, potential laboratory artifacts, and sequencing
      contaminants either prior to sequences being deposited in GenBank or before they
      are used for phylogenetic analyses. 

PMID- 23548804
TI  - Molecular investigation of multiple strain infections in patients with
      tuberculosis in Mubende district, Uganda.
AB  - Multiple strain tuberculosis (TB) infections are now an acceptable facet of
      tuberculosis epidemiology. Identification of patients infected with more than one
      strain gives an insight in disease dynamics at individual and population level.
      This study therefore aimed at identifying multiple strain infections among TB
      infected patients. Furthermore, to determine factors associated with multiple
      strain infections in Mubende district of Uganda. A total of 72 Mycobacterium
      tuberculosis isolates from patients at Mubende regional referral hospital were
      characterized using 15 loci MIRU-VNTR, Spoligotyping and deletion analysis.
      Genotypic and epidemiological data were analyzed using MIRU-VNTR plus,
      Bionumerics software version 6.1 and an exact logistic regression model
      respectively. Eight (11.1%) of the 72 patients had mixed TB infections. Five were
      exclusively pulmonary mixed infections while three had both pulmonary and extra
      pulmonary infections (Compartmentalized TB infections). Unlike previous studies
      that have linked this phenomenon to Beijing strains, multiple strains in this
      study belonged to T2-Uganda, X2 and T1 lineages. Two of the pulmonary mixed
      infections were resistant to rifampicin or isoniazid. All except one were HIV
      positive, newly diagnosed cases and urban residents of Mubende district. The
      study revealed that one in nine urban dwelling, HIV/TB co-infected patient were
      infected with more than one M. tuberculosis strains. The molecular findings give
      indications of a vital component of the disease dynamics that is most likely
      under looked at clinical level.

PMID- 23548805
TI  - ACL reconstruction in patients aged 40 years and older: a systematic review and
      introduction of a new methodology score for ACL studies.
AB  - BACKGROUND: Treatment of the anterior cruciate ligament (ACL)-deficient knee in
      older patients remains a core debate. PURPOSE: To perform a systematic review of
      studies that assessed outcomes in patients aged 40 years and older treated with
      ACL reconstruction and to provide a new methodological scoring system that is
      directed at critical assessment of studies evaluating ACL surgical outcomes: the
      ACL Methodology Score (AMS). STUDY DESIGN: Systematic review. METHODS: A
      comprehensive literature search was performed from 1995 to 2012 using MEDLINE,
      EMBASE, and Scopus. Inclusion criteria for studies were primary ACL injury,
      patient age of 40 years and older, and mean follow-up of at least 21 months after
      reconstruction. Nineteen studies met the inclusion criteria from the 371
      abstracts from MEDLINE and 880 abstracts from Scopus. Clinical outcomes
      (International Knee Documentation Committee [IKDC], Lysholm, and Tegner activity
      scores), joint stability measures (Lachman test, pivot-shift test, and
      instrumented knee arthrometer assessment), graft type, complications, and
      reported chondral or meniscal injury were evaluated in this review. A new
      methodology scoring system was developed to be specific at critically analyzing
      ACL outcome studies and used to examine each study design. RESULTS: Nineteen
      studies describing 627 patients (632 knees; mean age, 49.0 years; range, 42.6
      60.0 years) were included in the review. The mean time to surgery was 32.0 months
      (range, 2.9-88.0 months), with a mean follow-up of 40.2 months (range, 21.0-114.0
      months). The IKDC, Lysholm, and Tegner scores and knee laxity assessment
      indicated favorable results in the studies that reported these outcomes. Patients
      did not demonstrate a significant difference between graft types and functional
      outcome scores or stability assessment. The mean AMS was 43.9 +/- 7.2 (range,
      33.5-57.5). The level of evidence rating did not positively correlate with the
      AMS, which suggests that the new AMS system may be able to detect errors in
      methodology or reporting that may not be taken into account by the classic level
      of evidence rating. CONCLUSION: Patients aged 40 years and older with an ACL
      injury can have satisfactory outcomes after reconstruction. However, the quality
      of currently available data is still limited, such that further well-designed
      studies are needed to determine long-term efficacy and to better inform our
      patients with regard to expected outcomes.

PMID- 23548806
TI  - Arthroscopic hip labral reconstruction with a gracilis autograft versus labral
      refixation: 2-year minimum outcomes.
AB  - BACKGROUND: There is high interest but very little evidence to support labral
      reconstruction of the hip. Purpose/ HYPOTHESIS: The purpose of this study was to
      determine the clinical effectiveness of arthroscopic hip labral reconstruction
      using gracilis autograft in the multistep surgeries for femoroacetabular
      impingement (FAI). The hypothesis was that patients undergoing arthroscopic hip
      labral reconstruction with gracilis autograft would have improvement in symptoms
      and function attributable to this procedure. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: A comparative retrospective review at a large medical
      facility was performed of patients who underwent labral reconstruction with a
      gracilis autograft (RECON group) and those who underwent labral refixation (REFIX
      group) between October 2008 and November 2009. Inclusion criteria were adult
      patients having undergone arthroscopic surgery for symptomatic cam-pincer FAI
      without advanced radiographic osteoarthritis, who had both acetabular and femoral
      osteoplasties with a minimum 2-year follow-up. Patient satisfaction and
      preoperative and postoperative nonarthritic hip scores (NAHS) were obtained.
      Predictive modeling, linear regression, and a nested case-control study were
      performed. RESULTS: A total of 54 patients met the inclusion criteria. The RECON
      group (n = 8; mean age, 34.6 years; range, 18-58 years) with an average 30-month
      follow-up (range, 24-37 months) and 100% participation reported a high level of
      patient satisfaction (7 high, 1 moderate). The mean NAHS improved by 50.5 points
      (P = .008) in the RECON group and 22.5 points (P < .0001) in the REFIX group;
      however, the preoperative NAHS was lower (P < .05) in the RECON group than in the
      REFIX group. Only the surgery group (RECON vs REFIX) and the preoperative NAHS
      were significantly associated with the NAHS at follow-up. The predictive model
      and linear regression revealed a 15.0- and 14.6-point increase, respectively, in
      the postoperative NAHS in the RECON group compared with the REFIX group. There
      were no major complications, revision surgeries, or conversion arthroplasties
      after labral reconstruction. CONCLUSION: Arthroscopic hip labral reconstruction
      with gracilis tendon autograft is a safe and effective procedure. Patients
      undergoing labral reconstruction may not necessarily have outcomes inferior to
      those of patients undergoing labral refixation despite more severe initial labral
      insufficiency.

PMID- 23548807
TI  - Ulnar collateral ligament reconstruction using bisuspensory fixation: a
      biomechanical comparison with the docking technique.
AB  - BACKGROUND: Many ulnar collateral ligament (UCL) reconstruction techniques have
      been created and biomechanically tested. Single-bundle reconstructions aim to re
      create the important anterior bundle of the UCL. To date, no technique has
      utilized suspensory fixation on the ulnar and humeral sides to create a single
      bundle reconstruction. HYPOTHESIS: The bisuspensory technique will restore valgus
      laxity to its native state, with comparable load-to-failure characteristics to
      the docking technique. STUDY DESIGN: Controlled laboratory study. METHODS: Six
      matched pairs of fresh-frozen cadaveric elbows were randomized to undergo UCL
      reconstruction using either the docking technique or a novel single-bundle
      bisuspensory technique. Valgus laxity and rotation measurements were quantified
      using a MicroScribe 3DLX digitizer at various flexion angles for the native
      ligament, transected ligament, and 1 of the 2 tested reconstructed ligaments.
      Laxity testing was performed from maximum extension to 120 degrees  of flexion.
      Each reconstruction was then tested to failure, and the method of failure was
      recorded. RESULTS: Valgus laxity was restored to the intact state at all degrees
      of elbow flexion for both the docking and bisuspensory techniques. In load-to
      failure testing, there was no significant difference with regard to stiffness,
      ultimate torque, ultimate torque angle, energy absorbed, and applied moment to
      reach 10 degrees  of valgus. Yield torques for the bisuspensory and docking
      reconstructions were 18.7 +/- 7.8 N.m and 18.6 +/- 4.4 N.m, respectively (P =
      .95). The ultimate torque for the bisuspensory technique measured 26.5 +/- 9.2
      N.m and for the docking technique measured 25.1 +/- 7.1 N.m (P = .78).
      CONCLUSION: The bisuspensory fixation technique, a reproducible single-bundle
      reconstruction, was able to restore valgus laxity to the native state, with
      similar load-to-failure characteristics as the docking technique. CLINICAL
      RELEVANCE: This reconstruction technique could be considered in a clinical
      setting as a primary method of UCL reconstruction or as a backup fixation method
      should intraoperative complications occur.

PMID- 23548808
TI  - The Arthroscopic Surgical Skill Evaluation Tool (ASSET).
AB  - BACKGROUND: Surgeries employing arthroscopic techniques are among the most
      commonly performed in orthopaedic clinical practice; however, valid and reliable
      methods of assessing the arthroscopic skill of orthopaedic surgeons are lacking.
      HYPOTHESIS: The Arthroscopic Surgery Skill Evaluation Tool (ASSET) will
      demonstrate content validity, concurrent criterion-oriented validity, and
      reliability when used to assess the technical ability of surgeons performing
      diagnostic knee arthroscopic surgery on cadaveric specimens. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: Content validity was determined
      by a group of 7 experts using the Delphi method. Intra-articular performance of a
      right and left diagnostic knee arthroscopic procedure was recorded for 28
      residents and 2 sports medicine fellowship-trained attending surgeons. Surgeon
      performance was assessed by 2 blinded raters using the ASSET. Concurrent
      criterion-oriented validity, interrater reliability, and test-retest reliability
      were evaluated. RESULTS: Content validity: The content development group
      identified 8 arthroscopic skill domains to evaluate using the ASSET. Concurrent
      criterion-oriented validity: Significant differences in the total ASSET score (P
      < .05) between novice, intermediate, and advanced experience groups were
      identified. Interrater reliability: The ASSET scores assigned by each rater were
      strongly correlated (r = 0.91, P < .01), and the intraclass correlation
      coefficient between raters for the total ASSET score was 0.90. Test-retest
      reliability: There was a significant correlation between ASSET scores for both
      procedures attempted by each surgeon (r = 0.79, P < .01). CONCLUSION: The ASSET
      appears to be a useful, valid, and reliable method for assessing surgeon
      performance of diagnostic knee arthroscopic surgery in cadaveric specimens.
      Studies are ongoing to determine its generalizability to other procedures as well
      as to the live operating room and other simulated environments.

PMID- 23548809
TI  - Inhibitory effect of mitomycin C on proliferation of primary cultured fibroblasts
      from human airway granulation tissues.
AB  - BACKGROUND: Airway granulation tissue and scar formation pose a challenge because
      of the high incidence of recurrence after treatment. As an emerging treatment
      modality, topical application of mitomycin C has potential value in delaying the
      recurrence of airway obstruction. Several animal and clinical studies have
      already proven its feasibility and efficacy. However, the ideal dosage has still
      not been determined. OBJECTIVES: To establish a novel method for culturing
      primary fibroblasts isolated from human airway granulation tissue, and to
      investigate the dose-effect of mitomycin C on the fibroblast proliferation in
      vitro, so as to provide an experimental reference for clinical practitioners.
      METHODS: Granulation tissues were collected during the routine bronchoscopy at
      our department. The primary fibroblasts were obtained by culturing the explanted
      tissues. The cells were treated with different concentrations of mitomycin C
      (0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml) for 5 min followed by additional 48-hour
      culture before an MTT assay was performed to measure cell viability. RESULTS: MTT
      assay showed that mitomycin C reduced cell viability at all tested
      concentrations. The inhibitory ratios were 10.26, 26.77, 32.88, 64.91 and 80.45%
      for cells treated with mitomycin C at 0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml,
      respectively. CONCLUSIONS: Explant culture is a reliable method for culturing
      primary fibroblasts from human airway granulation tissue, and mitomycin C can
      inhibit proliferation of the fibroblasts in vitro.

PMID- 23548811
TI  - The giant leap and small steps to better reperfusion in ST-segment elevation
      myocardial infarction patients.

PMID- 23548810
TI  - A meta-analysis of social capital and health: a case for needed research.
AB  - Social capital refers to various levels of social relationships formed through
      social networks. Measurement differences have lead to imprecise measurement. A
      meta-analysis of eligible studies assessing the bivariate association between
      social capital and self-reported health and all-cause mortality was performed.
      Thirty-nine studies met inclusion criteria, showing social capital increased odds
      of good health by 27 percent (95% confidence intervals [CI] =21%, 34%). Social
      capital variables, reciprocity increased odds of good health by 39 percent (95%
      CI = 21%, 60%) and trust by 32 percent (95% CI =19%, 46%). Future research
      suggests operationalizing measures by assessing differences by race/ethnicity,
      gender and socioeconomic status. 

PMID- 23548812
TI  - Authors' reply.

PMID- 23548813
TI  - Calf bioimpedance spectroscopy for determination of dry weight in hemodialysis
      patients: effects on hypertension and left ventricular hypertrophy.
AB  - BACKGROUND/AIMS: Dry weight estimation in hemodialysis patients is still a
      substantial problem. Despite meticulous clinical assessment, fluid overload is
      common, leading to hypertension and left ventricular hypertrophy (LVH). Segmental
      calf bioimpedance spectroscopy (cBIS) is a novel tool for dry weight assessment.
      Here we tested the hypothesis, that its clinical routine use reduces arterial
      hypertension and left ventricular mass. METHODS: Left ventricular mass
      (determined by magnetic resonance imaging), blood pressure and antihypertensive
      medication (defined daily doses, ddd) were assessed at baseline (BL). Thereafter
      post-dialytic target weight was reduced until cBIS-defined dry weight was reached
      (DW). During a 6-month follow up, DW was re-evaluated monthly by cBIS and end
      dialytic weight was adjusted correspondingly. At the end, left ventricular mass,
      blood pressure and antihypertensive medication were determined a 3rd time (follow
      up, FU). RESULTS: Eleven out of 15 patients were available for analysis after 6
      months. Left ventricular mass showed a declining trend during the study period
      (Mean+/-SD; BL 145+/-54 g; DW 142+/-55 g; FU 137+/-52 g; p=0.61, linear mixed
      model). Comparable results were obtained for systolic blood pressure (BL 158+/-18
      mmHg; DW 144+/-19 mmHg; FU 149+/-21 mmHg; p=0.07), and antihypertensive
      medication (BL 3.28+/-2.82ddd; DW 2.86+/-2.81ddd; FU 3.36+/-3.05ddd; p=0.37).
      CONCLUSIONS: We conclude that attainment of dry weight assessed by cBIS tends to
      reduce left ventricular mass and blood pressure while antihypertensive medication
      remains unchanged. While the study was underpowered, its results provide an
      important hypothesis generating data basis for the design of larger studies.

PMID- 23548814
TI  - Two novel vitamin D receptor modulators with similar structures exhibit different
      hypercalcemic effects in 5/6 nephrectomized uremic rats.
AB  - BACKGROUND/AIMS: Vitamin D receptor modulators (VDRMs) are indicated for
      secondary hyperparathyroidism in chronic kidney disease (CKD). Clinical
      observations demonstrate that VDRM therapy provides cardiovascular (CV) benefit
      in CKD. Current on-market VDRMs have a narrow therapeutic index at 1- to 4-fold
      [hypercalcemic toxicity vs. parathyroid hormone (PTH)-suppressing efficacy].
      Hypercalcemia leads to the need for frequent drug dose titration and serum
      calcium (Ca) monitoring. A VDRM with a wider therapeutic index and beneficial CV
      effects will be clinically useful. METHODS: Two structurally similar VDRMs were
      tested in the 5/6 nephrectomized (NX) rats with elevated PTH, endothelial
      dysfunction and left ventricular hypertrophy. RESULTS: VS-110 and VS-411 at 0.01
      1 MUg/kg (i.p. 3 times/week for 2 weeks) suppressed serum PTH effectively. VS-411
      raised serum Ca with an 11% increase at 0.01 MUg/kg (therapeutic index = ~1
      fold), while VS-110 did not raise serum Ca even at 1 MUg/kg (therapeutic index
      >50-fold). VS-110 improved endothelium-dependent aortic relaxation in a dose
      dependent manner and significantly reduced left ventricular fibrosis without
      affecting serum Ca. VS-411 also exhibited effects on the CV parameters, but was
      less potent at the high doses with severe hypercalcemia. VS-110 and VS-411
      specifically activated the reporter gene via a chimeric receptor containing the
      VDR ligand binding domain with EC(50) <0.1 nM. CONCLUSIONS: Structurally similar
      VDRMs can exhibit distinctly different hypercalcemic effects in 5/6 NX uremic
      rats. While differences exist for the Ca and CV effects of VS-110 and VS-411, the
      clinical implications are unclear. VS-110's results are promising but clinical
      outcome studies need to be performed.

PMID- 23548815
TI  - State of the science of endocrine disruptors.

PMID- 23548816
TI  - Dimensions of subcortical infarcts associated with first- to third-order branches
      of the basal ganglia arteries.
AB  - BACKGROUND: It has been described that lacunar infarct is characterized by its
      smallish size (15-20 mm) in the axial plane. However, the size of the basal
      ganglia artery responsible for this type of infarct is uncertain. Detection of
      small arterial occlusion is not possible with current angiography, hindering
      correlation of arterial occlusion with subcortical infarct size. Recently,
      investigators have published microangiographic templates of arteries supplying
      the basal ganglia. These templates display first-order (proximal) to third-order
      (distal) branching of these arteries and can help with estimating the likely site
      of arterial disease in subcortical infarcts. We correlated the dimensions of
      subcortical infarcts with the order of arterial branching described in a
      microangiographic template. Such data may provide further clues about the type of
      arteries associated with subcortical infarcts and assist in refining the concept
      of lacunar infarction. METHOD: Patients with subcortical infarcts on MR imaging
      (MRI) admitted to our institution between 2009 and 2011 were included in the
      study. Infarcts were manually segmented and registered to a standard brain
      template. These segmented infarcts were scaled and overlapped with published
      microangiographic templates, and used by 6 raters who independently estimated the
      branching order of arterial disease that might result in these infarcts. We used
      regression analysis to relate these ratings to infarct dimensions. RESULTS: Among
      777 patients, there were 33 (58% male) patients with subcortical infarcts. The
      mean age was 63.1 +/- 15.1 years. Infarct dimensions for the groups were as
      follows: group 1 (first-order branch): height 37.6 +/- 7.4 mm, horizontal width
      21.2 +/- 11.6 mm, anterior-posterior length 36.8 +/- 20.1 mm; group 2 (second
      order branch): height 25.2 +/- 7.9 mm, horizontal width 16.6 +/- 22.8 mm,
      anterior-posterior length 16.1 +/- 8.0 mm; group 3 (third-order branch): height
      11.6 +/- 5.7 mm, axial width 5.3 +/- 3.1 mm, anterior-posterior length 5.5 +/-
      3.8 mm. Increasing vessel branching order (from large to small vessels) was
      linearly and negatively associated with infarct height (beta = -16.7 mm per
      change in branching order disease, 95% CI -20.3, -13.1 mm, p < 0.01) and anterior
      posterior length (beta = -16.8 mm per change in branching order disease, 95% CI 
      23.2, -10.5 mm, p < 0.01). DISCUSSION: Based on MRI infarct dimensions and a
      microangiographic template, it may be possible to estimate the branching order of
      the artery involved in subcortical infarcts. Further, our small data set suggests
      that reliance on an axial dimension of 15-20 mm may not be the best approach to
      classifying lacunar infarct. This finding needs to be confirmed in a larger data
      set.

PMID- 23548817
TI  - Clinician-identified depression in community settings: concordance with
      structured-interview diagnoses.
AB  - BACKGROUND: Relatively little is known about the prevalence and correlates of
      overdiagnosis of depression in community settings. This study examined the extent
      to which individuals with clinician-identified depression in the community meet
      the criteria for DSM-IV major depressive episodes (MDE) and characteristics of
      these individuals. METHODS: In a sample of 5,639 participants with clinician
      identified depression drawn from the 2009-2010 United States National Survey of
      Drug Use and Health, the proportion of participants who met the 12-month MDE
      criteria, ascertained by a structured interview, and variations in MDE diagnosis
      across different groups of participants were examined. Mental health profiles and
      service use of participants who met the MDE criteria were compared to those who
      did not meet these criteria. RESULTS: Only 38.4% of participants with 12-month
      clinician-identified depression met the 12-month MDE criteria. Older adults were
      less likely than younger adults to meet the criteria - only 14.3% of those 65
      years old or older met the criteria, whereas participants with more education and
      those with poorer overall health were more likely to meet the criteria.
      Participants who did not meet the 12-month MDE criteria reported less distress
      and impairment in role functioning and used fewer services. A majority of both
      groups, however, were prescribed and used psychiatric medications. CONCLUSIONS:
      Depression overdiagnosis and overtreatment is common in community settings in the
      USA. There is a need for improved targeting of diagnosis and treatments of
      depression and other mental disorders in these settings.

PMID- 23548818
TI  - First study of microdeletions in the Y chromosome of Algerian infertile men with
      idiopathic oligo- or azoospermia.
AB  - The human Y chromosome is essential for human sex determination and
      spermatogenesis. The long arm contains the azoospermia factor (AZF) region.
      Microdeletions in this region are responsible for male infertility. The objective
      of this study was to determine the frequency of Y microdeletions in Algerian
      infertile males with azoospermia and oligoasthenoteratozoospermia syndrome (OATS)
      and to compare the prevalence of these abnormalities with other countries and
      regions worldwide. A sample of 80 Algerian infertile males with a low sperm count
      (1-20 * 10(6) sperms/ml) as well as 20 fertile male controls was screened for Y
      chromosome microdeletions. 49 men were azoospermic and 31 men had OATS. Genomic
      DNA was isolated from blood and polymerase chain reaction was carried out with a
      set of 6 AZFa, AZFb and AZFc STS markers to detect the microdeletions as
      recommended by the European Academy of Andrology. Among the 80 infertile men
      screened for microdeletion, 1 subject was found to have microdeletions in the
      AZFc (sY254 and sY255) region. The deletion was found in azoospermic subjects
      (1/49, 2%). The overall AZF deletion frequency was low (1/80, 1.3%). AZF
      microdeletions were observed neither in the OATS group nor in the control group.
      The frequency of AZF microdeletions in infertile men from Algeria was comparable
      to those reported in the literature. We suggest analyzing 6 STS in the first step
      to detect Y microdeletions in our population.

PMID- 23548819
TI  - Female same gender stalking: a brief review of the literature and case report.
AB  - The authors analyze a rare case of female same gender stalking that came to their
      observation as forensic psychiatry experts. Despite previously only heterosexual
      experiences, the woman, who was 30 in 2002, had three intimate same gender
      relationships in succession from 2002 to 2009: she broke off with each woman in
      order to take up with another. When she separated from the third woman she began
      violent persecutory behavior against her, in the form of harassment coming under
      the heading of stalking, and was reported to the authorities. In treatment with
      SSRI since 2003 for an anxiety disorder with panic episodes, she had been taking
      the drugs irregularly during the stalking period. At the end of the third
      relationship, after she had violently attacked her girlfriend she was advised by
      her family to present to a Hospital center in Northern Italy. There, she was
      diagnosed with a "Narcissistic Paranoid Personality Disorder", and it was
      hypothesized that the SSRI she was taking could have induced hypo/manic episodes
      and disinhibition in the woman, who had previously been heterosexual. At this
      hospital, mood stabilizers were prescribed. The defending lawyer therefore
      applied for a forensic psychiatry assessment, claiming that the persecutory
      behavior against the third girlfriend was induced by taking SSRI. In Italy the
      penal code specifies the recognition of abolished or diminished liability for
      crimes if a correlation between the mental disease and the crime can be
      demonstrated, if the disease was in course at the time of the crime, and if the
      motives behind the crime and the disease can be shown to be linked. In short, if
      the crime can be shown to be a symptom of the disease. But the forensic
      psychiatry assessment demonstrated that despite the presence of some factors of a
      psychopathological nature, the motives underlying the harassment were
      attributable to the woman's existential history and personality structure rather
      than to psychopathological causes. She was therefore judged guilty of the crime
      of stalking and a plea for a reduced sentence was granted. In this case, the
      gender of the stalker and victim seemed to be irrelevant.

PMID- 23548820
TI  - Small interfering RNA targeting Toll-like receptor 9 protects mice against
      polymicrobial septic acute kidney injury.
AB  - BACKGROUND/AIMS: Although recent reports suggest that Toll-like receptor (TLR) 9
      is associated with the pathogenesis of polymicrobial septic acute kidney injury
      (AKI), it is still unclear whether and how renal TLR9 is involved in the
      development of polymicrobial septic AKI. This study aimed to determine whether
      the expression of TLR9 in mouse renal cells is related to the development of
      polymicrobial septic AKI. METHODS: The efficacy of small interfering RNA (siRNA)
      targeting TLR9 was tested in a cultured murine macrophage cell line (RAW264.7
      cells). The most potent siRNA was transfected into mice using the hydrodynamic
      method prior to the induction of polymicrobial septic AKI being induced by cecal
      ligation and puncture (CLP). TLR9 knockdown was determined by real-time
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western
      blotting in RAW264.7 cells and kidney tissues. The levels of serum creatinine and
      blood urea nitrogen (BUN) and the renal histopathology assessment were determined
      at 6-, 12-, and 24-hour time points after CLP, and renal cell apoptosis was
      studied at 24 h. The 4- and 7-day survival rates of mice were also observed.
      RESULTS: We found that mice developed AKI in our model of polymicrobial sepsis,
      despite fluid and antibiotic resuscitation, which resembles human sepsis. siRNA
      to TLR9 successfully silenced the induction of renal TLR9 gene and protein
      expression following CLP. Effective silencing of renal TLR9 expression decreased
      renal cell apoptosis, mitigated the severity of AKI, and increased the survival
      of mice. CONCLUSIONS: Our data demonstrates the induction of TLR9 expression in
      mouse kidney tissue following CLP. Renal cell apoptosis and AKI in our model of
      polymicrobial sepsis are dependent on TLR9. Thus, TLR9 may play a critical role
      in the pathophysiology of polymicrobial septic AKI.

PMID- 23548821
TI  - Centimeter-long Ta3N5 nanobelts: synthesis, electrical transport, and
      photoconductive properties.
AB  - Centimeter-long Ta3N5 nanobelts were synthesized by a reaction of centimeter-long
      TaS3 nanobelt templates with flowing NH3 at 800  degrees C for 2 h. The nanobelts
      have cross-sections of about 50 * 100 nm(2), and lengths up to 0.5 cm. A field
      effect transistor (FET) made of a single Ta3N5 nanobelt was fabricated on
      silica/silicon substrate. The electric transport of the individual nanobelt
      revealed that the nanobelt is a semiconductor with a room-temperature resistivity
      of 11.88 Omega m, and can be fitted well with an empirical formula rho = 10831
      exp(-T/43.8) - 22.6, where rho is resistivity (Omega m) and T is absolute
      temperature (K). The FET showed decent photoconductive performance under light
      irradiation in the range 250-630 nm. The photocurrent increased by nearly 10
      times the dark current under 450 nm light irradiation at an applied voltage of
      5.0 V.

PMID- 23548822
TI  - Terminal myelocystocele: a series of 30 cases and review of the literature.
AB  - OBJECTIVE: Terminal myelocystocele is a rare form of spinal dysraphism. We report
      on the clinical and radiological features, surgical procedures and outcome of
      myelocystocele. METHODS: Thirty patients, with an age range of 1 month to 15
      years, which included 16 (53.3%) male children, had undergone surgery for
      terminal myelocystocele between 2000 and 2010. We had retrospectively analyzed
      their data. All patients had a swelling in the lumbosacral region which had a
      healthy skin cover. Twenty (66.7%) patients had presented with weakness, while 10
      (33.7%) patients had no deficits at all. Bladder bowel involvement was evident in
      12 (40%) cases. All patients had undergone excision of the meningocele sacs, the
      tethering bands were lysed, and filum was detethered. Ventriculoperitoneal shunt
      was done in 3 (10%) patients. Complications like pseudomeningocele were seen in 6
      (20%) patients, cerebrospinal fluid leak in 4 (13.3%) patients, and meningitis
      and surgical site infection in 1 (3.3%) patient each. The mean follow-up period
      was 15.2 (1-60) months. The status of all patients with no preoperative deficits
      remained unchanged. Out of 20 patients with motor weakness, 12 (60%) had
      improvement; worsening was observed in 1 patient. CONCLUSIONS: Though rare, the
      possibility of myelocystocele should be kept in mind when treating lumbosacral
      region masses as they have a better prognosis when compared with other masses in
      the region due to spinal dysraphism. We recommend early surgery in all diagnosed
      cases.

PMID- 23548823
TI  - Cardiotoxicity of cisplatin-based chemotherapy in advanced non-small cell lung
      cancer patients.
AB  - Cardiotoxicity is a well known consequence of cancer chemotherapy. Cisplatin
      based combinations are standard regimens in the therapy of advanced non-small
      cell lung cancer. Administration of cisplatin-containing chemotherapy causes
      significant oxidative and nitrosative stress in some patients. Cardiac blood
      biomarkers can be used to evaluate cardiac status, may help to identify patients
      at risk myocardial damage evaluation and are able to detect subclinical, early
      stage cisplatin-induced cardiotoxicity. The relevance of cardiovascular
      complications in cancer patients and identification of individual risk factors
      for developing cardiovascular toxicity merit further evaluation and a longer
      follow-up is needed.

PMID- 23548824
TI  - Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in
      experimental allergic asthma.
AB  - We compared the effects of bone marrow-derived mononuclear cells (BMMCs) and
      mesenchymal stromal cells (MSCs) on airway inflammation and remodeling and lung
      mechanics in experimental allergic asthma. C57BL/6 mice were sensitized and
      challenged with ovalbumin (OVA group). A control group received saline using the
      same protocol. Twenty-four hours after the last challenge, groups were further
      randomized into subgroups to receive saline, BMMCs (2*10(6)) or MSCs (1*10(5))
      intratracheally. BMMC and MSC administration decreased cell infiltration,
      bronchoconstriction index, alveolar collapse, collagen fiber content in the
      alveolar septa, and interleukin (IL)-4, IL-13, transforming growth factor (TGF)
      beta and vascular endothelial growth factor (VEGF) levels compared to OVA-SAL.
      Lung function, alveolar collapse, collagen fiber deposition in alveolar septa,
      and levels of TGF-beta and VEGF improved more after BMMC than MSC therapy. In
      conclusion, intratracheal BMMC and MSC administration effectively modulated
      inflammation and fibrogenesis in an experimental model of asthma, but BMMCs was
      associated with greater benefit in terms of reducing levels of fibrogenesis
      related growth factors.

PMID- 23548825
TI  - Subacute cutaneous lupus erythematosus induced and exacerbated by proton pump
      inhibitors.
AB  - BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) can be induced by
      numerous drugs. We report 3 cases of SCLE induced by proton pump inhibitors
      (PPIs). OBJECTIVE: To highlight a rare cutaneous side effect induced by a
      frequently prescribed drug such as a PPI. CASE REPORTS: Case 1 was a 30-year-old
      man who developed multiple annular plaques over the trunk and lower limbs 1 month
      after the initiation of pantoprazole. Antinuclear antibodies (ANA) were positive
      with anti-Ro/SSA and anti-La/SSB antibodies, and histology confirmed the
      diagnosis. Clinical improvement was achieved 8 weeks after the discontinuation of
      pantoprazole and the introduction of a treatment combining topical steroids and
      hydroxychloroquine. Lesions relapsed when pantoprazole was accidentally
      rechallenged. The second case was a 31-year-old woman, 28 weeks pregnant, who
      presented erythematous annular plaques over the trunk 7 weeks after starting
      esomeprazole. ANA and anti-Ro/SSA antibodies were positive, and the histology was
      compatible with SCLE. Fetal ultrasound was normal. She was treated with topical
      and oral steroids and hydroxychloroquine. Clinical improvement was achieved 4
      weeks after the discontinuation of esomeprazole. The third case was a 57-year-old
      woman with systemic erythematosus lupus presenting annular and psoriasiform
      lesions on the trunk for 15 months. She was treated successively with
      hydroxychloroquine, azathioprine, mycophenolate mofetil and methotrexate with
      prednisone. A review of her drug history revealed the introduction of omeprazole
      a few weeks before the first appearance of skin lesions and omeprazole was
      contraindicated. CONCLUSION: SCLE should systematically be suspected in case of
      eruption after the introduction of PPI. The risk of fetal cardiac complications
      is important in pregnant women.

PMID- 23548826
TI  - The relation between decreased glomerular filtration rate and nonvalvular atrial
      fibrillation.

PMID- 23548827
TI  - Cardiovascular risk and mineral bone disorder in patients with chronic kidney
      disease.
AB  - The term chronic kidney disease-mineral bone disorder has been coined recently to
      highlight that the disturbed mineral and bone metabolism is a major contributor
      to vascular calcification and finally cardiovascular disease. This syndrome is
      characterized by clinical, biochemical and/or histological findings, i.e. i)
      biochemical alterations in the homeostasis of calcium, phosphate and their key
      player parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), klotho
      and vitamin-D, ii) the occurrence of vascular and/or soft tissue calcification,
      and iii) an abnormal bone structure and/or turnover. Apart from the combined and
      synergistic action of "traditional" and uremia-related risk factors, promoters
      and inhibitors of calcification have to be considered as well. This review will
      focus on the disturbed mineral metabolism as the triggering force behind
      distortion of vascular integrity and cardiovascular malfunction in CKD patients.

PMID- 23548828
TI  - Professor Peter Berner (15 November 1924 to 17 November 2012).

PMID- 23548829
TI  - Induction of genes encoding NADPH oxidase components and activation of IFN
      regulatory factor-1 by prolactin in fish macrophages.
AB  - The role played by prolactin (PRL) in fish immunity is scant. We report here that
      stimulation of the Atlantic salmon monocytic cell line SHK-1 with native salmon
      PRL resulted in activation of the respiratory burst and induction of the
      expression of the genes encoding the phagocyte NADPH oxidase components p47phox,
      p67phox and gp91phox, and the transcription factor IFN regulatory factor-1 (IRF
      1). Interestingly, the pharmacologic inhibition of the Jak/Stat signaling pathway
      with AG490 blocked reactive oxygen species (ROS) production, and the induction of
      genes encoding the NADPH oxidase components and IRF-1 in PRL-activated SHK-1
      cells. In addition, PRL promoted the phosphorylation of Stat and induced the DNA
      binding activity of IRF-1. These results, together with the presence of several
      consensus target motifs for Stat and IRF-1 in the promoter of the tilapia p47phox
      gene, suggest that PRL regulates p47phox gene expression in fish through the
      activation of these two key transcription factors. Taken together, our results
      demonstrate that PRL induces the expression of the genes encoding the major
      phagocyte NADPH oxidase components and ROS production in fish macrophages via the
      JAK2/Stat/IRF-1 signaling pathway. 

PMID- 23548830
TI  - Haemodiafiltration results in similar changes in intracellular water and
      extracellular water compared to cooled haemodialysis.
AB  - BACKGROUND/AIMS: Intradialytic hypotension is the most common complication of
      modern day haemodialysis (HD). Convective modalities, including
      haemodiafiltration (HDF) are reported to result in greater cardiovascular
      stability compared to standard HD, which has been suggested to be due to improved
      solute transport between compartments. We therefore investigated the effect of
      treatment on body water by bioimpedance. METHODS: We measured the change in
      extracellular water (ECW) and intracellular water (ICW) in 263 outpatients
      attending for HD using cooled dialysate and 134 patients for HDF. RESULTS:
      Patient cohorts were matched for demographics, dialysate composition,
      ultrafiltration rate, and session duration. The fall in systolic blood pressure
      following HD was -11.8 mm Hg (-25.3 to 2.3) and not different from that following
      HDF -12 mm Hg (-27 to 6). Similarly there were no differences in pretreatment
      serum sodium and dialysate sodium gradient [HD 1 mmol/l (-1 to 3) vs. HDF 2
      mmol/l (1 to 4)], or change in serum sodium posttreatment [HD 0 mmol/l (-2 to 2)
      vs. HDF 1 mmol/l (-1 to 3)]. There were no differences in ICW or ECW
      pretreatment, and following treatment the reduction in ICW and ECW did not differ
      [ICW HD -3.5% (-5.7 to -1.8) vs. -4.1% (-6.0 to -1.7), ECW HD -7.1% (-9.4 to 
      4.7) vs. HDF -7.1% (-9.7 to -4.9)]. CONCLUSION: We were unable to demonstrate any
      advantage for HDF over HD using cooled dialysate in terms of changes in blood
      pressure during a treatment session, or differences in the relative changes in
      ICW or ECW volumes.

PMID- 23548831
TI  - An open-label safety study of first-line bevacizumab in combination with standard
      chemotherapy in Chinese patients with metastatic colorectal cancer treated in an
      expanded access program in Taiwan.
AB  - OBJECTIVE: An increased risk of serious adverse effects related to bevacizumab
      has been observed in many Western studies for metastatic colorectal cancer. To
      evaluate the safety of bevacizumab in Chinese patients, a safety study was
      conducted in Taiwan. METHODS: Bevacizumab was provided by the Expanded Access
      Program in combination with first-line chemotherapy per investigator's choice.
      The primary objective is the safety profile, particularly the targeted adverse
      events such as proteinuria, bowel perforation, hypertension, wound healing
      complication, thromboembolism and bleeding. The second objectives include time to
      disease progression and overall survival time. Patients with major surgical
      procedure performed within the 28 days of bevacizumab were excluded from this
      study. RESULTS: Forty patients were eligible for intent-to-treat analysis. The
      overall rate of objective response and disease control was 55.2 and 81.6%. The
      median time to disease progression and overall survival were 11.9 and 22.9
      months. The actuarial 2-year survival was 46.6%. Regarding toxicity, 7 subjects
      (17.5%) had serious adverse effects related to study treatment. None of the
      patients in this cohort had arterial thrombotic events and bowel perforation.
      CONCLUSIONS: Bevacizumab demonstrates a similar activity and safety profile in
      Chinese patients. Life-threatening bowel complications were avoided in this study
      by excluding patients with major surgery within the first 28 days.

PMID- 23548832
TI  - Virtual reality exposure therapy does not provide any additional value in
      agoraphobic patients: a randomized controlled trial.
AB  - BACKGROUND: A number of studies have demonstrated the efficacy of virtual reality
      exposure therapy (VRET) in specific phobias, but research in seriously impaired
      patients with agoraphobia is lacking. In this randomized controlled trial with
      patients with agoraphobia and panic disorder, VRET and exposure in vivo were
      compared in terms of outcome and processes involved. METHODS: Patients with panic
      disorder with agoraphobia (n = 55) were randomly assigned to receive 4 sessions
      of cognitive behavioral therapy (CBT) followed by either 6 sessions of VRET or 6
      sessions of exposure in vivo or to a waiting list control condition. RESULTS:
      Analyses showed that both active treatment packages were significantly more
      effective than no treatment and that no differences between VRET and exposure in
      vivo were found in three out of four outcome measures. On the panic disorder
      severity scale, however, CBT plus exposure in vivo was more effective than CBT
      plus VRET. The results show clear synchrony of temporal processes involved in
      VRET and exposure in vivo on weekly avoidance measures and cognitive measures.
      Further, it was shown that initial changes in agoraphobic cognitions during the
      CBT phase predicted later changes in agoraphobic avoidance behavior. CONCLUSION:
      These data support the notion that therapeutic processes involved might be the
      same in VRET and exposure in vivo. However, given the slight superiority of
      exposure in vivo above VRET, the costs involved in the implementation of VRET and
      the lack of long-term follow-up, VRET cannot yet be recommended for patients with
      agoraphobia.

PMID- 23548833
TI  - The relationship between neurological worsening and lesion patterns in patients
      with acute middle cerebral artery stenosis.
AB  - BACKGROUND: Intracranial atherosclerotic disease is one of the most common causes
      of ischemic stroke especially in Asians, Hispanics and blacks. Although middle
      cerebral artery (MCA) stenosis is increasingly being recognized with the advent
      of magnetic resonance angiography (MRA) or transcranial Doppler ultrasonography,
      few studies have focused on acute neurological worsening (NW) in patients with
      MCA stenosis. We investigated the relationship between NW and lesion patterns
      detected by diffusion-weighted imaging (DWI). METHODS: We studied 44 consecutive
      patients out of a total of 2,863 consecutive patients who had symptomatic lesions
      in the territory of the MCA and in whom MRA and/or conventional angiography
      showed isolated MCA stenosis >=50% in the MCA trunk. Acute DWI lesion patterns
      were classified as follows: (1) pial artery territory infarcts (PAI); (2) small
      cortical and/or subcortical infarcts (SCS); (3) deep penetrating artery territory
      infarcts (DPI); (4) cortical border zone infarcts (CBZ), and (5) internal border
      zone infarcts (IBZ). NW was defined as worsening by >=2 points on the National
      Institutes of Health Stroke Scale (NIHSS) during the first 7 days. Functional
      outcome was assessed by the modified Rankin Scale (mRS) at 3 months after stroke
      onset. Poor outcome was defined as >=3 on the mRS. The severity of MCA stenosis
      on MRA was further categorized as 50-75% (moderate) and >75% or focal signal loss
      with the presence of distal MCA signal (severe). RESULTS: There were 14 patients
      (31.8%) who showed NW and 16 patients (36.3%) who showed poor outcomes. Nine of
      the 14 patients with NW showed poor outcomes (64.2%). The most frequent lesions
      in the present study were SCS (n = 16, 36.3%), followed by IBZ (n = 12, 27.2%)
      and DPI (n = 11, 25.0%). Prevalence of IBZ was significantly higher in the group
      with NW compared to that without NW (p = 0.0081), while the prevalence of SCS,
      DPI, PAI and CBZ did not differ between the two groups. Logistic regression
      analysis showed significantly high age- and sex-adjusted odds ratios (ORs) for NW
      only for IBZ (OR 10.9, p = 0.0051). The degree of stenosis did not correlate with
      NW and lesion patterns. CONCLUSIONS: Only IBZ among various lesion patterns
      correlated strongly with NW. IBZ are considered to be more associated with
      hemodynamic compromise, while embolic pathogeneses contribute more to CBZ or SCS.
      Early interventional medical treatments such as thrombolytic or anti-platelet
      therapy or stenting should be considered in cases of IBZ in MCA stenosis.

PMID- 23548834
TI  - Implementing systematic review at the National Toxicology Program: status and
      next steps.

PMID- 23548835
TI  - Gremlin is a downstream profibrotic mediator of transforming growth factor-beta
      in cultured renal cells.
AB  - BACKGROUND/AIMS: Chronic kidney disease is characterized by accumulation of
      extracellular matrix in the tubulointerstitial area. Fibroblasts are the main
      matrix-producing cells. One source of activated fibroblasts is the epithelial
      mesenchymal transition (EMT). In cultured tubular epithelial cells, transforming
      growth factor-beta (TGF-beta1) induced Gremlin production associated with EMT
      phenotypic changes, and therefore Gremlin has been proposed as a downstream TGF
      beta1 mediator. Gremlin is a developmental gene upregulated in chronic kidney
      diseases associated with matrix accumulation, but its direct role in the
      modulation of renal fibrosis and its relation with TGF-beta has not been
      investigated. METHODS: Murine renal fibroblasts and human tubular epithelial
      cells were studied. Renal fibrosis was determined by evaluation of key
      profibrotic factors, extracellular matrix proteins (ECM) and EMT markers by
      Western blot/confocal microscopy or real-time PCR. Endogenous Gremlin was
      targeted with small interfering RNA. RESULTS: In murine fibroblasts, stimulation
      with recombinant Gremlin upregulated profibrotic genes, such as TGF-beta1, and
      augmented the production of ECM proteins, including type I collagen. The blockade
      of endogenous Gremlin with small interfering RNA inhibited TGF-beta1-induced ECM
      upregulation. In tubular epithelial cells Gremlin also increased profibrotic
      genes and caused EMT changes: phenotypic modulation to myofibroblast-like
      morphology, loss of epithelial markers and in-duction of mesenchymal markers.
      Moreover, Gremlin gene silencing inhibited TGF-beta1-induced EMT changes.
      CONCLUSIONS: Gremlin directly activates profibrotic events in cul-tured renal
      fibroblasts and tubular epithelial cells. Moreover, endogenous Gremlin blockade
      inhibited TGF-beta-mediated matrix production and EMT, suggesting that Gremlin
      could be a novel therapeutic target for renal fibrosis.

PMID- 23548836
TI  - A unique form of haptoglobin produced by murine hematopoietic cells supports B
      cell survival, differentiation and immune response.
AB  - Haptoglobin (Hp), an acute phase reactant and major hemoglobin-binding protein,
      has a unique role in host immunity. Previously, we demonstrated that Hp-deficient
      C57BL/6J mice exhibit stunted development of mature T- and B-cells resulting in
      markedly lower levels of antigen-specific IgG. The current study identified
      leukocyte-derived pro-Hp as a relevant mediator of an optimal immune response.
      Reconstitution of Hp-/- mice with Hp+/+ bone marrow restored normal immune
      response to ovalbumin. Furthermore, transplanting a mixture of bone marrow
      derived from B-cell-deficient and Hp-deficient mice into Rag1-/-/Hp+/+ recipients
      resulted in mice with a defective immune response similar to Hp-/- mice. This
      suggests that Hp generated by the B-cell compartment, rather than by the liver,
      is functionally contributing to a normal immune response. Leukocytes isolated
      from the spleen express Hp and release a non-proteolytically processed pro-Hp
      that uniquely differed from liver-derived Hp by not binding to hemoglobin. While
      addition of purified plasma Hp to cultured B-cells did not alter responses, pro
      Hp isolated from splenocytes enhanced cellular proliferation and production of
      IgG. Collectively, the comparison of wild-type and Hp-deficient mice suggests a
      novel regulatory activity for lymphocyte-derived Hp, including Hp produced by B
      cells themselves, that supports in vivo survival and functional differentiation
      of the B-cells to ensure an optimal immune response.

PMID- 23548838
TI  - Exploring the role of space-defining objects in constructing and maintaining
      imagined scenes.
AB  - It has recently been observed that certain objects, when viewed or imagined in
      isolation, evoke a strong sense of three-dimensional local space surrounding them
      (space-defining (SD) objects), while others do not (space-ambiguous (SA)
      objects), and this is associated with engagement of the parahippocampal cortex
      (PHC). But activation of the PHC is classically associated with scene stimuli.
      The comparable neural response within PHC to both full scenes and single SD
      objects, led us to hypothesise that SD objects might play a more critical role in
      the construction and maintenance of scene representations than SA objects. To
      test this we used scene construction and deconstruction paradigms, where
      participants gradually built and maintained scenes using SD, SA and background
      (wall, floors) items. By examining the order in which each item was added (and
      later removed) to (and from) a scene, we could estimate the significance of each
      item type. In two different experiments, participants chose SD over SA objects
      and background items as the first and most critical item in their constructed
      scenes and, more generally, selected SD objects earlier than SA objects across
      the scene construction process. When deconstructing scenes, participants retained
      significantly more SD objects than SA objects, and the last remaining object
      across all scenes was highly likely to be an SD object. SD objects therefore
      enjoy a privileged role in scene construction and maintenance, and appear to be
      an essential building block of scenes.

PMID- 23548837
TI  - Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic
      targets in T cell anergy.
AB  - T cell anergy is one of the mechanisms contributing to peripheral tolerance,
      particularly in the context of progressively growing tumors and in tolerogenic
      treatments promoting allograft acceptance. We recently reported that early growth
      response gene 2 (Egr2) is a critical transcription factor for the induction of
      anergy in vitro and in vivo, which was identified based on its ability to
      regulate the expression of inhibitory signaling molecules diacylglycerol kinase
      (DGK)-alpha and -zeta. We reasoned that other transcriptional targets of Egr2
      might encode additional factors important for T cell anergy and immune
      regulation. Thus, we conducted two sets of genome-wide screens: gene expression
      profiling of wild type versus Egr2-deleted T cells treated under anergizing
      conditions, and a ChIP-Seq analysis to identify genes that bind Egr2 in anergic
      cells. Merging of these data sets revealed 49 targets that are directly regulated
      by Egr2. Among these are inhibitory signaling molecules previously reported to
      contribute to T cell anergy, but unexpectedly, also cell surface molecules and
      secreted factors, including lymphocyte-activation gene 3 (Lag3), Class-I-MHC
      restricted T cell associated molecule (Crtam), Semaphorin 7A (Sema7A), and
      chemokine CCL1. These observations suggest that anergic T cells might not simply
      be functionally inert, and may have additional functional properties oriented
      towards other cellular components of the immune system.

PMID- 23548839
TI  - Neural correlates of Machiavellian strategies in a social dilemma task.
AB  - In spite of having deficits in various areas of social cognition, especially in
      mindreading, Machiavellian individuals are typically very successful in different
      tasks, including solving social dilemmas. We assume that a profound examination
      of neural structures associated with decision-making processes is needed to learn
      more about Machiavellians' abilities in exploiting other people. More
      specifically, we predicted that high-Mach people would show elevated activity in
      the brain areas involved in reward-seeking, anticipation of risky situations, and
      inference making. To test this hypothesis, we used an fMRI technique to examine
      individuals as they played the Trust Game. In accordance with our predictions, we
      found consistent activation in high-Machs' thalamus and anterior cingulate cortex
      (player 1), and dorsal anterior insula/inferior frontal gyrus (player 2). We
      suggest that Machiavellians conduct specific neural operations in social dilemma
      situations that make them successful in exploiting others. Machiavellians may
      have cognitive heuristics that enable them to make predictions about the future
      reward in a basically risky and unpredictable situation.

PMID- 23548840
TI  - Using mass scaling of movement cost and resource encounter rate to predict animal
      body size-population density relationships.
AB  - The negative relationship between body mass and population abundance was
      documented decades ago and forms one of the most fundamental scaling-laws in
      ecology. However, current theory fails to capture observed variations and the
      subject continues to raise controversy. Here we unify empirically observed size
      abundance relationships with theory, by incorporating allometries in resource
      encounter rate and metabolic costs of movements. Fractal geometry is used to
      quantify the underlying resources distributions. Our model predicts that in
      environments packed with resources, body mass to population abundance
      relationships is less negative than the commonly assumed -3/4 power law. When
      resources are more patchily distributed, we predict a more negative exponent.
      These predictions are consistent with empirical observations. The current
      research provides an important step towards synthesizing metabolism, resource
      distribution and the global scaling of animal abundance, explaining why size
      abundance relationships vary among feeding guilds and ecosystems.

PMID- 23548841
TI  - Spontaneous perforation of pyometra: a report of seven cases and review of the
      literature.
AB  - BACKGROUND/AIMS: The spontaneous perforation of pyometra is very rare and is
      associated with a poor prognosis. The present study aimed to evaluate the
      clinical characteristics and prognostic factors for patient survival. PATIENTS
      AND METHODS: We reported on 7 patients with spontaneous rupture of pyometra. We
      also reviewed 47 additional published cases. Thus, all 54 patients were analyzed
      for mortality. RESULTS: We investigated the prognosis in 44 of 54 patients,
      excluding 8 patients with undocumented outcome and 2 who died of other diseases.
      The mortality rate was 25% (11 of 44). In univariate analysis, variables such as
      age, correct preoperative diagnosis, comorbidities, the presence of malignancy,
      and hysterectomy were not significant between surviving and deceased patients. In
      bacterial cultures from the peritoneal cavity, the most common etiological
      organisms were Escherichia coli and anaerobes such as Bacteroides and Peptococcus
      species. The rate of isolation of anaerobic bacteria was significantly increased
      in patients who died (odds ratio, 6.33; 95% confidence interval, 1.28-31.02; p =
      0.04). CONCLUSION: Antibiotic therapy for E. coli and anaerobes should be
      considered in patients with spontaneous perforation of pyometra.

PMID- 23548842
TI  - Outcome analysis of tubularized incised plate repair in hypospadias: is a
      catheter necessary?
AB  - OBJECTIVE: Tubularized incised plate (TIP) urethroplasty is performed by many
      pediatric urologists and has been widely accepted for repair of distal and mid
      shaft hypospadias. However, the role of urethral catheter placement in TIP repair
      remains controversial. In this study, the surgical outcomes of indwelling
      urethral catheter and non-catheter TIP repairs in boys with hypospadias were
      compared. METHODS: A total of 254 patients with primary distal and mid-shaft
      hypospadias underwent TIP repair and were evaluated retrospectively. A urethral
      catheter was placed in 103 patients (group A) and non-catheter repair was
      performed in 151 patients (group B). Information obtained included age, toilet
      training, chordee, type of hypospadias, presence or absence of a catheter, and
      postoperative complications. The complications recorded included wound infection,
      urinary tract infection, bladder spasm, urinary retention, urinary extravasation,
      meatal stenosis, urethral stricture, and urethrocutaneous fistula. RESULTS: There
      was no statistical difference in age, toilet training, chordee, hypospadias site,
      or performing surgeon between the two groups. The median follow-up time was 22
      and 24 months for groups A and B, respectively. The rate of bladder spasms (10.7
      vs. 0%, p < 0.001) and urinary tract infection (9.7 vs. 3.3%, p = 0.034) was
      significantly higher for group A than group B. Although the rate of urinary
      retention was higher in group B than in group A (4.0 vs. 0%), there was no
      statistically significant difference between the two groups (p = 0.084).
      Likewise, the incidence of urethrocutaneous fistula and meatal stenosis was not
      significantly different. CONCLUSION: Non-catheter TIP repair is feasible and
      positive outcomes can be achieved with minimal complications and less patient
      discomfort.

PMID- 23548844
TI  - The use of the chronic kidney disease epidemiology collaboration equation and
      global cardiovascular risk assessment in patients with atrial fibrillation.

PMID- 23548843
TI  - Statin use and calcific uremic arteriolopathy: a matched case-control study.
AB  - BACKGROUND: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is
      characterized by vascular calcification, thrombosis and intense inflammation.
      Prior research has shown that statins have anticalcification, antithrombotic and
      antiinflammatory properties; however, the association between statin use and CUA
      has not been investigated. METHODS: This matched case-control study included 62
      adult maintenance hemodialysis (HD) patients with biopsy-confirmed CUA diagnosed
      between the years 2002 and 2011 (cases). All cases were hospitalized at the time
      of diagnosis. Controls (n = 124) were hospitalized maintenance HD patients
      without CUA (matched to cases by gender and timing of hospitalization).
      Univariate and multivariable logistic regression models were applied to compute
      odds ratio (OR) and 95% confidence intervals (CI) for CUA in statin users, and
      also to examine previously described associations. RESULTS: The mean age of cases
      was 58 years. Most were females (68%), and of white race (64%). Statin use was
      more common in controls than in cases (39 vs. 19%, p < 0.01). Statin use was
      associated with lower odds of CUA in unadjusted (OR 0.38, 95% CI 0.18-0.79) and
      adjusted (OR 0.20, 95% CI 0.05-0.88) analyses. Hypercalcemia (OR 2.25, 95% CI
      1.14-4.43), hypoalbuminemia (OR 5.73, 95% CI 2.79-11.77), calcitriol use (OR
      5.69, 95% CI 1.02-31.77) and warfarin use (OR 4.30, 95% CI 1.57-11.74) were
      positively associated with CUA in adjusted analyses whereas paricalcitol and
      doxercalciferol were not (OR 1.33, 95% CI 0.54-3.27). CONCLUSION: Statin use may
      be negatively associated with odds of CUA. Further large prospective studies with
      attention to potential confounders are needed to confirm these findings.

PMID- 23548845
TI  - Working disability in Norwegian patients with vestibular schwannoma: vertigo
      predicts future dependence.
AB  - OBJECTIVE: We examined whether reduced hearing, tinnitus, dizziness, and
      unsteadiness affected the patients' ability to maintain work within a time frame
      of 2-10 years after diagnosis. METHODS: A total of 434 consecutive patients were
      followed at regular intervals. Data on symptoms were scored prospectively and
      dichotomized by visual analog scales for tinnitus and vertigo. Study design is
      retrospective. Hearing acuity was scored according to the Gardner-Robertson
      scale, and unsteadiness was measured on a balance platform. Patients were asked
      about working status, and scored as receiving governmental compensation for
      disability. RESULTS: Two hundred six patients were eligible for study. Of these,
      one died and nine were lost to follow-up. Ninety-seven patients received
      conservative management, 49 patients recieved gamma knife radiosurgery, and 50
      patients were treated by microsurgery. Mean follow-up time was 58.7 months
      (range, 20-132 months). There was a significant increase in the number of
      individuals receiving compensation during the study period (P < 0.0001). At
      baseline, the proportion of pension receivers was within same range as that of
      the age- and sex-matched Norwegian population (5.61% vs. 6.91%; case-control odds
      ratio, 0.82; 95% confidence interval 0.45-1.49; P = 0.51, not significant). At
      the final time point, the increase in the number of receivers deviated
      significantly from the reference population (case-control odds ratio, 3.80; 95%
      confidence interval 2.71-5.33; P <= 0.001). Examining symptoms at first
      presentation as predictors of future dependence revealed that vertigo and higher
      mean age were associated with a higher risk (P < 0.001 and P = 0.015,
      respectively). No other symptoms were predictive of dependence. CONCLUSIONS: In a
      prospectively followed cohort of Norwegian patients with vestibular schwannoma,
      vestibular complaints were significant predictors for becoming dependant of
      disability pension.

PMID- 23548846
TI  - Multicenter registry of liquid embolic treatment of cerebral aneurysms.
AB  - OBJECTIVE: The Cerebral Aneurysm Multicenter European Onyx trial was the first
      multicenter prospective case series using liquid embolization for cerebral
      aneurysms. It suggested a possible decreased risk for recanalization of smaller
      aneurysms compared with coil embolization. After publication of that trial, the
      Onyx HD embolic agent, injection devices, and treatment protocols have all been
      updated and improved to increase efficacy and decrease adverse events. We present
      the results from a multicenter registry of liquid embolization treatments using
      the current method and materials. We hypothesize that the evolution of this
      technique will result in lower complication and recanalization rates when
      compared with earlier series. METHODS: Surgeons performing liquid embolization
      submitted data about consecutive patients and procedures. The data provided were
      used to determine what characteristics were associated with durable occlusion and
      recanalization. RESULTS: One hundred thirteen patients at 25 medical centers
      throughout the United States underwent liquid embolization. Of these, 110 had
      follow-up data of at least 6 months. Seventeen patients (15%) experienced a
      complication and 4 (3.5%) experienced procedure-related ischemic stroke or death.
      Nine patients (8.1%) had aneurysm recanalization and 5 (4.5%) required
      retreatment. All retreatments were accomplished with further liquid embolization
      and were stable at the last follow-up angiogram available. Those with durable
      occlusion had smaller aneurysm size (mean, 10 mm vs. 17 mm) (P = 0.03) and were
      de novo (P = 0.02). CONCLUSIONS: Recent advances in liquid embolization have led
      to decreased recanalization and complications. Liquid embolization is more likely
      to achieve a durable result in smaller aneurysms that have not been previously
      treated.

PMID- 23548847
TI  - Aspirin and aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Recent evidence has suggested a potential beneficial effect of aspirin
      on the risk of aneurysm rupture. This benefit must be weighed against its
      potential adverse effects as an antiplatelet agent in the setting of acute
      aneurysmal subarachnoid hemorrhage (SAH). METHODS: A total of 747 consecutive
      patients with cerebral aneurysms were reviewed, comparing demographics, aneurysm
      features, presenting clinical and radiographic grades, vasospasm, and outcome at
      1 year between patients with aneurysmal SAH taking aspirin on presentation and
      those who were not. RESULTS: The rate of hemorrhagic presentation was
      significantly greater in patients not taking aspirin (40% vs. 28%; P = 0.016).
      Among 274 patients presenting with aneurysmal SAH, there was no significant
      difference in presenting clinical (Hunt and Hess) and radiographic (Fisher) grade
      between patients taking aspirin and those who were not. There was also no
      significant difference in the rate of subsequent angiographic and delayed
      cerebral ischemia. Multivariate analysis of outcome at 1 year found only
      increasing age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.12),
      Hunt and Hess grade (OR 3.01, 95% CI 1.81-5.03), and associated hypertension (OR
      3.30, 95% CI 1.39-7.81) to be statistically significant risk factors for poor
      outcome (death or dependence), whereas aspirin use was not associated with poor
      outcome (OR 1.19, 95% CI 0.35-4.09; P = 0.78). CONCLUSIONS: In the present study,
      patients taking aspirin had a lower rate of hemorrhagic presentation. In
      addition, taking aspirin did not adversely impact presenting clinical grade or
      radiographic grade, vasospasm, and outcome in the setting of aneurysmal SAH.

PMID- 23548848
TI  - Endoscopic-assisted resection of intracranial epidermoid tumors.
AB  - OBJECTIVE: Intracranial epidermoid tumors are epithelially derived lesions that
      may present particular challenges to neurosurgeons, often encasing critical
      neurovascular structures and extending into multiple subarachnoid cisterns. We
      aimed to evaluate our recent experience with endoscopic assistance to craniotomy
      with microsurgical resection of these lesions. METHODS: A retrospective review of
      patients undergoing endoscopic-assisted craniotomy for resection of an epidermoid
      tumor at the Keck School of Medicine of University of Southern California between
      2009 and 2012 was conducted. In all patients, the surgical approach and tumor
      resection were first performed microscopically. This was followed by use of an
      angled endoscope to facilitate further inspection and additional resection of
      tumor using a two-surgeon technique. RESULTS: Twelve patients undergoing 13
      consecutive endoscopic-assisted craniotomies were included in the analysis. The
      mean patient age was 45 years. The mean maximal tumor diameter was 4.0 cm (range,
      2.4-5.8 cm). Surgery was for recurrent epidermoid in 6 of 13 cases (46%).
      Epidermoid tumor location included the cerebellopontine angle (9 patients, 75%),
      fourth ventricle (2 patients, 17%), and third ventricle (1 patient, 8%). Surgical
      approaches included retrosigmoid craniotomy (8 patients), suboccipital craniotomy
      (1 patient), suboccipital craniotomy with supracerebellar approach (1 patient),
      extradural temporopolar approach (1 patient), and subtemporal approach (1
      patient). In 11 of 13 cases (85%), additional tumor was identified upon
      inspection with an angled endoscope, facilitating additional tumor resection in
      each case. Gross or deliberate near total resection was achieved in 7 of 13 cases
      (54%). Four patients (31%) had improvement of cranial nerve function.
      Postoperative neurological deficits included transient abducens and oculomotor
      nerve paresis in one patient each. CONCLUSIONS: The endoscope is a safe and
      effective adjunct to the microscope in facilitating additional inspection and
      further resection of epidermoid tumors. Endoscopic-assisted surgery is
      particularly useful for identifying and removing additional tumor located around
      surgical corners.

PMID- 23548849
TI  - Acrodysostosis and spinal canal involvement.
AB  - BACKGROUND: Acrodysostosis is a rare syndrome characterized by peripheral
      dysostosis, nasal hypoplasia, and frequently mental retardation. Only two adult
      cases of acrodysostosis have been reported to have neurological symptoms. CASE
      DESCRIPTION: We report one additional adult case that presented with signs of
      spinal cord compression from spinal stenosis, and make the first histologic
      description in the literature of the bony anomalies seen in acrodysostosis. The
      patient had a T3 to T5 laminectomy and experienced a complete recovery.
      CONCLUSIONS: Special attention should be given to these patients to detect signs
      of spinal stenosis, as early decompression can lead to neurological recovery.

PMID- 23548850
TI  - Posttraumatic stress disorder: neurocircuitry and implications for potential deep
      brain stimulation.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling
      psychiatric disorder that is notoriously difficult to treat. At some point in
      their lifetimes, 5-8% of men, 10-14% of women, and up to a quarter of combat
      veterans carry this diagnosis. Despite pharmacological and behavioral therapies,
      up to 30% of patients are still symptomatic 10 years after initial diagnosis.
      Recent advances in imaging have implicated changes in the limbic and autonomic
      corticostriatopallidothalamocortical (CSPTC) circuitry in the pathogenesis of
      this disease. Deep brain stimulation modulates CSPTC circuits in movement and
      other neuropsychiatric disorders. In this review, we discuss the salient clinical
      features and neurocircuitry of PTSD and propose a neuromodulation strategy for
      the disorder. 

PMID- 23548851
TI  - Access to chemical data used in regulatory decision making.

PMID- 23548852
TI  - Effects of a multidisciplinary stress treatment programme on patient return to
      work rate and symptom reduction: results from a randomised, wait-list controlled
      trial.
AB  - BACKGROUND: To evaluate the efficacy of a multidisciplinary stress treatment
      programme. METHODS: General practitioners referred 198 employed patients on sick
      leave with symptoms of persistent work-related stress. Using a waitlisted
      randomised controlled trial design, the participants were randomly divided into
      the following three groups: the intervention group (IG, 69 participants);
      treatment-as-usual control group (TAUCG, 71 participants), which received 12
      consultations with a psychologist, and the waitlisted control group (WLCG, 58
      participants). The stress treatment intervention consisted of nine 1-hour
      sessions conducted over 3 months. The goals of the sessions were the following:
      (1) identifying relevant stressors; (2) changing the participant's coping
      strategies; (3) adjusting the participant's workload and tasks, and (4) improving
      workplace dialogue. Each participant also attended a mindfulness-based stress
      reduction (MBSR) course for 2 h a week over 8 weeks. RESULTS: The IG and TAUCG
      showed significantly greater symptom level (Symptom Check List 92) reductions
      compared to the WLCG. Regarding the return to work (RTW) rate, 67% of
      participants in the IG returned to full-time work after treatment, which was a
      significantly higher rate than in the TAUCG (36%) and WLCG (24%). Significantly
      more participants in the IG (97%) increased their working hours during treatment
      compared with the participants in the control groups, TAUCG (71%) and WLCG (64%).
      CONCLUSIONS: The stress treatment programme--a combination of work place-focused
      psychotherapy and MBSR--significantly reduced stress symptom levels and increased
      RTW rates compared with the WLCG and TAUCG.

PMID- 23548853
TI  - Could craniometric measurements explain the growth of the superior sagittal
      sinus?
AB  - OBJECTIVE: The objective of this study was to relate demographic variables and
      craniometric measures with measurements of the superior sagittal sinus (SSS) at
      different points along the path of the SSS. The findings were then discussed with
      regards to theories of skull growth. METHODS: We studied 33 skulls with known
      demographic characteristics and measured various craniometric parameters and
      distances related to the specific dimensions of the SSS. These data were
      statistically analyzed, and the results are presented. RESULTS: Of the 33 cadaver
      samples, 16 were female and 17 were male, aged between 28 and 87 years at the
      time of death. The cross-sectional area of the SSS measured at the coronary
      suture was positively correlated with the biauricular length. In addition, when
      measured 1.5 cm above the torcula, the cross-sectional area of the SSS was
      negatively correlated with the distance between the medial epicanthi.
      CONCLUSIONS: The relationships found may indicate that the growth of the SSS is
      proportional to the activity of each segment of the SSS that occurs along its
      path.

PMID- 23548854
TI  - Water-swallowing test: screening for aspiration in stroke patients.
AB  - BACKGROUND AND PURPOSE: The water-swallowing test (WST) is frequently used in
      clinical practice as a functional assessment to detect aspiration and prevent
      pneumonia. It is a standardized test used all over the world, but the amount of
      water given varies depending on the examiner. Furthermore, there are very few
      reports on the simultaneous performance of the WST and videofluorography (VF).
      This study compared the amount of swallowed water to investigate the reliability
      of WST to exclude aspiration following acute stroke. METHODS: We assessed 111
      stroke patients (65 men and 46 women) with suspected dysphagia/difficulty in
      swallowing and performed VF upon obtaining consent from the patients and their
      families. Patients were aged between 20 and 98 years (65.6 +/- 13.4 years); 64
      had cerebral infarction, 26 cerebral hemorrhage, 13 subarachnoid hemorrhage, and
      8 had other cerebrovascular disease. The time from stroke onset to VF was 16.6 +/
      10.3 days (range, 2-55). WSTs using 5, 10, 30, and 60 ml and the modified WST
      (MWST) were performed during VF. RESULTS: We found that the number of instances
      of choking, cough, wet voice, and aspiration increased with higher amounts of
      water. The sensitivity and specificity of WST for aspiration ranged from 34.8 to
      55.7% and from 78.9 to 93.2%, respectively. The MWST, which used only 3 ml of
      water, yielded a sensitivity of 55.3% and a specificity of 80.8% for aspiration.
      There was a positive correlation between the time for one swallow and age, but
      there was no difference between genders. There was also no connection between
      clinical findings during WST or the presence of aspiration with the number of
      swallows, swallowing speed, or time for one swallow. CONCLUSIONS: WSTs are not as
      powerful as VF as a screening instrument in acute stroke. WSTs with more water
      detected aspiration with greater sensitivity, but there is no justification for
      overconfidence when investigating aspiration. We recommend using WST as well as
      VF to investigate swallowing in stroke patients.

PMID- 23548855
TI  - Effect of magnesium supplementation on carotid intima-media thickness and flow
      mediated dilatation among hemodialysis patients: a double-blind, randomized,
      placebo-controlled trial.
AB  - OBJECTIVES: The aim of the present study was to determine the efficacy of oral
      magnesium (Mg) supplementation on endothelial function through evaluation of
      carotid intima-media thickness (cIMT), brachial artery flow-mediated dilatation
      (FMD), and C-reactive protein (CRP) among hemodialysis (HD) patients. METHODS:
      This randomized, controlled, double-blind clinical trial consisted of 54 patients
      on HD. One group was treated orally with 440 mg of Mg oxide 3 times per week for
      6 months (n = 29). The control group (n = 25) was given placebo using the same
      administration protocol. cIMT, FMD, serum calcium levels, phosphorus, lipid, CRP,
      and bicarbonate were measured at baseline and at 6 months in both groups.
      RESULTS: At 6 months, cIMT was significantly decreased in the Mg group (0.84 +/-
      0.13 mm at baseline and 0.76 +/- 0.13 mm at 6 months, p = 0.001). However, in the
      placebo group, cIMT was significantly increased (0.73 +/- 0.13 and 0.79 +/- 0.12
      mm, respectively, p = 0.003). When hypertension, diabetes mellitus, smoking,
      hyperlipidemia, and systemic lupus erythematosus were controlled for in the
      analysis, the effect of Mg remained significant in both groups (p = 0.000).
      CONCLUSION: Our results indicate that Mg might not improve endothelial function
      (CRP level and FMD) and that a decreased cIMT as a marker of atherosclerosis may
      be due to the inhibition of calcification through the regulation parathormone,
      calcium, and phosphorus.

PMID- 23548856
TI  - Allergy prevention via co-administration of intact food allergen and its epitope
      soup?

PMID- 23548857
TI  - Is repeat head computed tomography necessary in children admitted with mild head
      injury and normal neurological exam?
AB  - BACKGROUND: Children admitted following mild head injury (MHI) often undergo
      repeat head computed tomography (HCT) to identify progression of injury, although
      there is little evidence to support this practice. METHODS: From January 2007 to
      December 2009, we retrospectively reviewed the medical records of patients aged 2
      months to 18 years admitted with a diagnosis of MHI to a Level I Pediatric Trauma
      Center. Data including Glasgow Coma Scale, loss of consciousness, length of stay
      (LOS), and number and results of HCTs were analyzed. RESULTS: A total of 507
      patients were admitted with MHI and normal neurological exam; 389 had a normal
      and 118 had an abnormal initial HCT. The median LOS in the normal HCT group was
      17.68 h (5.47-109.68) and in the abnormal HCT group 36.63 h (10.15-192.40). The
      median number of HCTs in the normal HCT group was 1 (1-2) and in the abnormal HCT
      group 2 (1-5). CONCLUSIONS: Children admitted with MHI, abnormal initial HCT and
      normal neurological exam had longer LOS and more HCTs compared with children with
      normal initial HCTs. No patient in either group had any change in their
      management based on HCT. Therefore, repeat HCT may be unnecessary for patients
      with MHI and normal neurological exam.

PMID- 23548858
TI  - Obesity: the gateway to ill health - an EASO position statement on a rising
      public health, clinical and scientific challenge in Europe.

PMID- 23548859
TI  - Impaired brachial artery flow-mediated vasodilation in response to handgrip
      exercise-induced increases in shear stress in young smokers.
AB  - Smoking is an established risk factor for cardiovascular disease. It has also
      been shown to result in endothelial dysfunction as assessed by flow-mediated
      dilation (FMD) in response to reactive hyperemia (RH)-induced increases in shear
      stress. Handgrip exercise (HGEX) is an emerging alternative method to increase
      shear stress for FMD assessment (HGEX-FMD) and the purpose of this study was to
      identify the impact of smoking on HGEX-FMD in young healthy subjects. Brachial
      artery RH-FMD and HGEX-FMD (10-minute bout of HGEX) was assessed in eight smokers
      (S) and 14 non-smokers (NS) (age 21 +/- 2 years). Brachial artery diameter and
      mean blood velocity were assessed with echo and Doppler ultrasound, respectively.
      Shear stress was estimated by shear rate (SR = brachial artery blood
      velocity/diameter). The SR stimulus did not differ between groups for either test
      (RH-FMD (SR area under the curve until peak diameter measurement), p = 0.897;
      HGEX-FMD (average SR over 10-minute exercise bout), p = 0.599). The RH-FMD
      magnitude was not significantly different between groups (S: 7.7 +/- 2.2% vs NS:
      7.9 +/- 2.4%, p = 0.838); however, the HGEX-FMD magnitude was significantly
      impaired in smokers (S: 6.1 +/- 3.4% vs NS: 9.6 +/- 3.6%, p = 0.037). In
      conclusion, HGEX-FMD assessment detected vascular dysfunction in young healthy
      smokers while RH-FMD did not. This suggests that HGEX-FMD may be useful in the
      early detection of smoking-induced impairments in endothelial function. Further
      research is required to explore this phenomenon in other populations and to
      isolate underlying mechanisms.

PMID- 23548861
TI  - Poly (lactic acid)-chitosan-collagen composite nanofibers as substrates for blood
      outgrowth endothelial cells.
AB  - In this work, the attachment, viability and functionality of rat Blood Outgrowth
      Endothelial Cells (rBOEC) and genetically modified rBOEC (rBOEC/eNOS-GFP), which
      over express endothelial nitric oxide synthase (eNOS), were investigated on
      Poly(lactic acid) (PLA)-chitosan and PLA-chitosan-collagen nanofibrous scaffolds.
      Both the cell types displayed good attachment, remained viable and functional on
      both scaffolds. Moreover, incorporation of collagen in the scaffold helped in
      sustaining the rBOEC for upto one week, although collagen was not found necessary
      for rBOEC/eNOS-GFP. We conclude that PLA-chitosan based nanofibrous scaffolds can
      be a potential candidate for BOEC based wound healing applications.

PMID- 23548862
TI  - Preparation and characterization of poly(pluronic-co-L-lactide) nanofibers for
      tissue engineering.
AB  - In this work, a new kind of biodegradable poly(pluronic-co-L-lactide) (Pluronic
      PLLA copolymers) was successfully prepared by melt-polycondensation method from L
      lactide, Pluronic and isophorone diisocyanate (IPDI). The obtained copolymers
      were characterized by (1)H NMR, FT-IR, X-ray, and TGA/DTA. Meanwhile, three
      dimensional (3-D) porous scaffolds based on Pluronic-PLLA were prepared by the
      electrospinning method, the factors of concentration, flow rate and voltage that
      influence the formation of the Pluronic-PLLA nanofibers were studied and the
      structure of Pluronic-PLLA nanofibers were investigated by scanning electron
      microscopy (SEM). MTT results revealed that the Pluronic-PLLA scaffolds had good
      biocompatibility and nontoxicity. Morphological study using fluorescence
      micrographs and scanning electron microscopy showed that in vitro osteoblast cell
      culture demonstrated the electrospun Pluronic-PLLA composite scaffolds could
      provide a suitable environment for good cell attachment. These results suggested
      that such Pluronic-PLLA nanofibers membranes might have prospective applications
      in tissue engineering field.

PMID- 23548863
TI  - Thermal inactivation and conformational lock studies on horse liver alcohol
      dehydrogenase: structural mechanism.
AB  - Horse liver alcohol dehydrogenase (HLADH) is a two subunits metal enzyme that has
      two catalytic sites and two coenzyme domains for each subunit. These subunits are
      connected together by coenzyme domains. In this study, we investigated the number
      and sequences of residues that participated in interface locks of HLADH. For this
      purpose, the kinetics of thermal inactivation of HLADH were studied in a 50 mM
      pyrophosphate buffer, pH 8.8, using ethanol as a substrate and NAD(+) as a
      cofactor. The temperature range was between 46 degrees C and 55 degrees C and the
      conformational lock was developed based on the Poltorak theory and analysis of
      the curves was done by the conformational lock method for oligomeric enzymes. The
      conformational lock number of HLADH was 2 when calculated experimentally. The
      results were confirmed by the Ligplot program computations. Using computational
      method it was shown that there are two patches binding sites at the interface and
      they spread over two regions of each chain. In this study we also proposed a
      thermal denaturation mechanism for HLADH by using different techniques such as UV
      Vis fluorescence and circular dichroism (CD) spectroscopy and dynamic light
      scattering (DLS). The subunits are dissociated and several intermediates appeared
      during inactivation through increasing the temperature. DLS measurement was
      performed to study the changes in hydrodynamic radius during thermal
      inactivation. The three distinct zones that were shown by DLS were also confirmed
      by fluorescence and CD techniques.

PMID- 23548864
TI  - Evaluation of reference genes for qRT-PCR gene expression studies in whole blood
      samples from healthy and leukemia-virus infected cattle.
AB  - Real-time quantitative reverse transcription PCR (qRT-PCR) is the method of
      choice to investigate the alterations in gene expression involved with BLV
      pathogenesis. However, the reliability of qRT-PCR data critically depends on
      proper normalization to a set of stably expressed reference genes. The aim of the
      study was to validate the expression stability of ten candidate reference genes
      in RNA isolated from whole blood cells of BLV-negative and BLV-positive cows with
      hematological abnormalities. The rankings of the candidate genes according to
      their expression stability were calculated using BestKeeper, NormFinder and
      qBase(PLUS) software with implemented geNorm(PLUS) algorithm. The results showed
      that two genes are sufficient for normalization of qRT-PCR studies in whole blood
      RNA isolated from cows infected with BLV. According to geNorm, UCHL5 and RPLP0
      were the best choice, but taking into account possible intergroup variation,
      NormFinder recommended RPLP0 and B2M as a most suitable pair. The overall ranking
      based on the geometric mean of the ranking numbers from each method separately
      showed UCHL5, RPLP0 and TBP as the most stable candidate reference genes. In
      addition, all three methods unanimously pointed at the commonly used ACTB and
      GAPDH as the least stable genes. These results further emphasize the need to
      accurately validate candidate reference genes before use in gene expression qRT
      PCR studies.

PMID- 23548865
TI  - Two Mx genes identified in European sea bass (Dicentrarchus labrax) respond
      differently to VNNV infection.
AB  - Mx proteins are key components of the antiviral state triggered by interferon
      type I in response to viral infections. In this study, two different Mx genes
      have been identified in European sea bass (Dicentrarchus labrax), and their
      sequences were cloned and characterized. MxA cDNA consists of 1881 bp coding for
      a putative 626 aminoacids protein, while MxB cDNA has 1920 bp and results in a
      protein with 639 residues. Their corresponding genomic sequences contain 3538 bp
      and 5326 bp, respectively, and both present 12 exons and 11 introns. The
      expression patterns of the two Mx genes after an in vivo challenge with the viral
      nervous necrosis virus (VNNV), a serious pathogen in farmed European sea bass,
      have been characterized by real-time PCR. The results showed interesting
      differences in the transcription profile of both Mx, thus suggesting a
      differential role for each Mx isoform in the immune response of European sea bass
      to VNNV, and most likely in the general viral response of this species.

PMID- 23548866
TI  - Ex vivo expansion of canine cytotoxic large granular lymphocytes exhibiting
      characteristics of natural killer cells.
AB  - Canine NK cells still are not well-characterized due to the lack of information
      concerning specific NK cell markers and the fact that NK cells are not an
      abundant cell population. In this study, we selectively expanded the canine
      cytotoxic large granular lymphocytes (CLGLs) that exhibit morphologic, genetic,
      and functional characteristics of NK cells from normal donor PBMCs. The cultured
      CLGLs were characterized by a high proportion of CD5(dim) expressing cells, of
      which the majority of cells co-expressed CD3 and CD8, but did not express
      TCRalphabeta and TCRgammadelta. The phenotype of the majority of the CLGLs was
      CD5(dim)CD3(+)CD8(+) TCRalphabeta(-)TCRgammadelta(-)CD4(-)CD21(-)CD11c(+/
      )CD11d(+/-)CD44(+). The expression of mRNAs for NK cell-associated receptors
      (NKG2D, NKp30, NKp44, Ly49, perforin, and granzyme B) were highly upregulated in
      cultured CLGLs. Specifically, NKp46 was remarkably upregulated in the cultured
      CLGLs compared to PBMCs. The mRNAs for the NKT-associated iTCRalpha gene in CLGLs
      was present at a basal level. The cytotoxic activity of the CLGLs against canine
      NK cell-sensitive CTAC cells was remarkably elevated in a dose-dependent manner,
      and the CLGLs produced large amounts of IFN-gamma. The antitumor activity of
      CLGLs extended to different types of canine tumor cells (CF41.Mg and K9TCC-pu
      AXC) without specific antigen recognition. These results are consistent with
      prior reports, and strongly suggest that the selectively expanded CLGLs represent
      a population of canine NK cells. The results of this study will contribute to
      future research on canine NK cells as well as NK cell-based immunotherapy.

PMID- 23548867
TI  - The calcimimetic calindol prevents high phosphate-induced vascular calcification
      by upregulating matrix GLA protein.
AB  - BACKGROUND: High serum phosphate (Pi) levels represent a major issue in dialysis
      patients, because associate with secondary hyperparathyroidism, vascular
      calcification (VC), and cardiovascular outcomes. In this population,
      calcimimetics are used to control secondary hyperparathyroidism,
      hyperphosphatemia, and, more recently, to delay the progression of VC. The aim of
      this in vitro study was to investigate the direct effects of the calcimimetic
      calindol on the progression of high Pi-induced VC. METHODS: Rat vascular smooth
      muscle cells (VSMCs) were incubated with high Pi concentrations, and the effects
      of calindol were investigated on vascular calcium deposition and VSMC
      osteoblastic differentiation. RESULTS: Calindol inhibited calcium deposition
      concentration-dependently with a maximal inhibition of 64.0 +/- 5.2% achieved at
      100 nM. Furthermore, calindol was able to partially prevent the high Pi-induced
      bone morphogenic protein 2 (BMP-2) expression upregulation (32.4 +/- 4.6% of
      inhibition; p < 0.01). Interestingly, the pretreatment with calindol enhanced the
      matrix Gla protein (MGP) gene expression significantly, compared to high Pi
      treated cells (40.2 +/- 6.6% of increase, p < 0.01). CONCLUSIONS: In conclusion,
      we demonstrated that the calcimimetic calindol prevents high Pi-induced VC by
      affecting osteoblastic differentiation in vitro. In particular, the inhibitory
      effect of calindol on VC is probably due to its stimulatory role on the calcium
      sensing receptor, leading to an increase in the synthesis of MGP by VSMCs.

PMID- 23548868
TI  - ASURA (PHB2) interacts with Scc1 through chromatin.
AB  - Sister chromatid cohesion mediated by the cohesin complex is essential for
      faithful chromosome segregation. Previously we reported that PHB2
      (prohibitin2/ASURA), a multifunctional protein, has a role in sister chromatid
      cohesion. Nevertheless, how ASURA is involved in sister chromatid cohesion still
      remains unclear. The present co-immunoprecipitation analysis reveals that ASURA
      interacts with cohesin subunit Scc1 in vivo. We show that ASURA associates with
      chromatin in a similar manner as Scc1 throughout the cell cycle. Furthermore, our
      observation using the Fucci (fluorescent ubiquitination-based cell cycle
      indicator) system indicates that ASURA is important for cohesin maintenance at
      early mitosis. We have also identified that the conserved PHB domain is
      responsible for chromatin targeting of ASURA. Our results suggest that the
      regulation of sister chromatid cohesion is mediated by ASURA binding to
      chromatin, where ASURA might be involved in cohesin protection through ASURA-Scc1
      interactions.

PMID- 23548869
TI  - The Impact of Idle Time in the Classroom: Differential Effects on Children With
      ADHD.
AB  - OBJECTIVE: Studies have identified an exacerbation of ADHD deficits under
      specific laboratory conditions. Less is known about the significance of such
      contextual factors in relation to everyday functioning in naturalistic settings.
      METHOD: This study investigated the differential impact of classroom "idle time"-
      periods when students are not actively engaged or waiting for a task--on the
      behavior of 31 children with ADHD (25 boys and 6 girls; aged 6-12 years) and 31
      sex- and age-matched typically developing classmates, who were simultaneously
      observed in their normal classroom during two school days. RESULTS: Both groups
      experienced the same amount of idle time (12% of the time). During idle time,
      however, levels of hyperactivity and noisiness increased significantly more in
      children with ADHD than in their classmates (p < .05). CONCLUSION: Findings
      highlight the differential susceptibility of ADHD children to classroom idle
      time. Classroom interventions might consider targeting specifically these periods
      to reduce disruptive behavior in these children.

PMID- 23548870
TI  - A retrospective survey of childhood ADHD symptomatology among adult narcoleptics.
AB  - OBJECTIVE: This study examined the retrospective history of childhood ADHD
      symptomatology in an adult narcoleptic population (Narcolepsy Group [NG]: n =
      161) compared with a control group (CG: n = 117). METHOD: Both groups completed
      the Wender Utah Rating Scale (WURS), a retrospective self-report questionnaire
      indicating the presence of childhood ADHD symptomatology in adults. RESULTS:
      Childhood ADHD symptoms were significantly greater in NG than CG (p < .001).
      Joint prevalence calculations of childhood ADHD symptomatology in NG were more
      than 8 to 15 times greater than expected. Among NG, those individuals with a
      greater score on the WURS, indicative of childhood ADHD symptomatology, also had
      shorter sleep onsets on the Multiple Sleep Latency Test, a common objective
      measure of sleepiness, t(97) = -7.11, p < .05. CONCLUSION: It appears that self
      reported childhood ADHD symptomatology history among adult narcoleptics is
      common. Future research is warranted with adult narcoleptics to elucidate the
      true nature of this.

PMID- 23548871
TI  - Idiopathic erythrocytosis in dialysis patients: a case report and literature
      review.
AB  - Anemia is a common complication in end-stage renal disease (ESRD) patients. On
      the other hand, idiopathic erythrocytosis is extremely rare, with only a few
      cases reported in the literature. We present a case of erythrocytosis that
      developed after initiating hemodialysis. A 68-year-old male with a history of
      ESRD secondary to diabetes presented with erythrocytosis that started a few
      months after initiating dialysis in the absence of having received erythropoietin
      stimulating agents or iron supplements. His erythropoietin level was elevated,
      with a negative JAK2 mutation. Blood gases showed normal oxygen and CO(2), with
      slightly elevated carboxyhemoglobin. Tiny foci in both kidneys were noted,
      representing vascular calcifications or renolithiasis. There was no radiological
      evidence of neoplasms or cysts. After excluding secondary causes, a diagnosis of
      idiopathic erythrocytosis was made. The patient underwent intermittent
      phlebotomies during dialysis, and his hemoglobin went from 18.5 to 14 mg/dl.
      Erythrocytosis in ESRD patients is very rare. So far, there is no complete
      understanding of the underlying pathophysiology; however, there seem to be
      multiple possible reasons for an increased erythropoietin level. Phlebotomy is a
      successful and easy way to control erythrocytosis in such patients. Angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers, currently being
      used in posttransplant erythrocytosis, might also be considered.

PMID- 23548872
TI  - Comparison of three versions of Partin tables to predict final pathologic stage
      in a Chinese cohort: a decision curve analysis.
AB  - PURPOSE: To compare Partin tables (PTs) 1997, 2001, and 2007 for their clinical
      applicability in a Chinese cohort based upon a decision curve analysis (DCA).
      METHODS: Clinical and pathologic data of 264 consecutive Chinese patients with
      clinically localized prostate cancer were used. These patients underwent open
      radical prostatectomy between 2005 and 2011. DCA quantified the net benefit of
      different PT versions relating to specific threshold probabilities of established
      capsular penetration (ECP), seminal vesicle involvement (SVI), and lymph node
      involvement (LNI). RESULTS: Overall, ECP, SVI, and LNI were recorded in 23.1,
      10.2, and 6.1%, respectively. When the threshold probability was below the
      prevalence for LNI and ECP predictions, the DCA favored the 2007 version versus
      the 1997 version for SVI. CONCLUSIONS: DCA indicates that for low threshold
      probability, decision models are useful to discriminate the performance
      differences of three PT versions, although net benefit differences were not
      apparent. For high threshold probability, there may not be an important benefit
      from the use of PTs and the current analysis cannot translate into meaningful net
      gains differences.

PMID- 23548873
TI  - Geographical distribution of dental caries prevalence and associated factors in
      young adults in Finland.
AB  - Oral health of the young has been reported to be associated with the place of
      residence, due to differences in socio-economic status. The results of studies on
      the effect of fluoride in drinking water on caries prevalence have been
      contradictory. The main aim of our study was to investigate the geographical
      distribution of dental caries prevalence in Finland and analyse possible
      regional, associated factors. Oral health of 13,564 men born between 1990 and
      1992 was screened using a method based on criteria of the World Health
      Organization for epidemiological studies by 15 calibrated dentists in 20/24
      garrisons of the Finnish Defence Forces in 2011. Mean DMFT and DT values in
      provinces were calculated. Multilevel analysis was applied to the data using
      generalized linear mixed models and a logit link function. The binary outcome
      variable was the cariological treatment need (yes/no) and the garrison was
      treated as random effect. Mean DMFT and DT values varied significantly between
      provinces in Finland. Increased levels of fluoride in drinking water, Swedish as
      the main language in the municipality, and living in urban areas were protective
      factors against cariological treatment need. Dentist density did not affect
      caries prevalence. The geographical distribution of dental caries further
      supported estimates of the protective effects of high fluoride levels in drinking
      water, Swedish as the main language in the municipality, as well as living in
      urban areas. Effect of fluoride on caries prevalence still exists, and
      association with the socio-economic status was confirmed. 

PMID- 23548874
TI  - The perceptions of young rural drivers in NSW, Australia of speeding and
      associated risk: a mixed methods study.
AB  - The study, using mixed methodology, examined perceptions of risk associated with
      speeding in young rural people. Focus groups discussions (age range 16-24) in
      which speeding was identified as often being an involuntary driving behaviour,
      informed the development of a survey instrument. The survey was conducted with
      two groups of young people, one rural (n=217) and another semi-rural (n=235). The
      results from both the focus groups and surveys indicate that young rural drivers
      had specific attitudes to speeding, when compared with other risk factors for
      crashing. Speeding behaviour was viewed as both acceptable and inevitable. Males
      and those from a rural area viewed speeding, and reducing trip time when compared
      to that of a peer, to be less risky than did females and those who lived in a
      semi-rural area. Speeding was considered to be less risky than drink driving.
      These perceptions of speeding may contribute to the crash rates on rural roads
      involving young, local drivers and need to be considered in interventions or
      educational programmes which aim to reduce the rural road crash rate.

PMID- 23548875
TI  - What factors influence older people in the decision to relinquish their driver's
      licence? A discrete choice experiment.
AB  - PURPOSE: To investigate the relative importance of a number of key factors that
      influence older people in the decision to relinquish their driver's licence.
      METHOD: A discrete choice experiment (DCE) was administered as an online survey
      to Australian adults, 65 years plus (N=114) who drive, recruited from an online
      panel. The survey was composed of three main sections. (A) The Adelaide Driving
      Self Efficacy Scale to assess confidence in driving. The scale is generated from
      individual's responses about confidence in their driving ability in various
      situations. (B) The DCE in which respondents were presented with a series of
      hypothetical binary choice situations and asked to indicate in which situation
      they would be more likely to relinquish their driving licence. (C) Socio
      demographic and health status questions. A conditional logit regression model was
      adopted to analyse the DCE data. RESULTS: Older people would be more likely to
      relinquish their driver's licence due to advanced age, low confidence in driving
      ability and in situations where their local doctor advises them to cease driving.
      Other transport options availability and the cost of public transport were not
      found to be influential to this decision. CONCLUSIONS: Factors pertaining to the
      individual themselves including advanced old age and low confidence in driving
      ability may be more influential than environmental factors such as availability
      of other transport options and the cost of public transport in an older person's
      decision to relinquish their driving licence.

PMID- 23548876
TI  - Chronic evaluation of a clinical system for deep brain stimulation and recording
      of neural network activity.
AB  - BACKGROUND/AIMS: In conjunction with therapeutic stimulation, next-generation
      deep brain stimulation (DBS) devices may offer the ability to record and analyze
      neural signals, providing for unprecedented insight into DBS effects on neural
      networks. This work was conducted to evaluate an implantable, clinical-grade
      system that permits concurrent stimulation and recording using a large animal
      (ovine) model recently developed to study DBS for epilepsy. METHODS: Following
      anesthesia and 1.5-tesla MRI acquisition, unilateral anterior thalamic and
      hippocampal DBS leads were implanted (n = 3) using a frameless stereotactic
      system. Chronic, awake recordings of evoked potentials (EPs) and local field
      potentials were collected with the implanted device and analyzed off-line.
      RESULTS: Hippocampal EPs were stable over long-term (>1 year) recording and
      consistent in morphology and latency with prior acute results. Thalamic and
      hippocampal DBS produced both excitatory and inhibitory network effects that were
      stimulation site and parameter dependent. Free roaming recordings illustrated
      periods of highly correlated activity between these two structures within the
      circuit of Papez. CONCLUSIONS: These results provide further insight into
      mechanisms of DBS therapy for epilepsy and an encouraging demonstration of the
      capabilities of this new technology, which in the future, may afford unique
      opportunities to study human brain function and neuromodulation mechanism of
      action.

PMID- 23548877
TI  - The performance of the revised Major Depression Inventory for self-reported
      severity of depression--implications for the DSM-5 and ICD-11.

PMID- 23548878
TI  - Pancreatitis potentially associated drugs as a risk factor for post-endoscopic
      retrograde cholangiopancreatography pancreatitis: a prospective cohort study.
AB  - OBJECTIVES: The aim of this study was to assess the role of known risk factors
      and specifically evaluate the role of pancreatitis potentially associated drugs
      as potential risk factors for post-endoscopic retrograde cholangiopancreatography
      (ERCP) pancreatitis (PEP). METHODS: This was a prospective, single-center cohort
      study conducted in a tertiary university hospital. All eligible ERCP procedures
      within a 16-month period were evaluated, and all interventions, patient
      characteristics, and medications used were documented. The association of
      potential risk factor with PEP was investigated with univariable analyses. Those
      statistically significant were entered in a multivariable regression model.
      RESULTS: Three hundred eighteen ERCP procedures were studied. Post-ERCP
      pancreatitis occurred in 28 patients (8.8%). Twenty-three potential risk factors
      were studied in univariable analyses, and 3 of them were found to be nominally
      statistically significant. These 3 factors were independently associated with PEP
      in the multivariable model and included the use of pancreatitis potentially
      associated drugs, belonging to Badalov classes I or II, during the last month
      before ERCP (odds ratio [OR], 4.39; 95% confidence interval [CI], 1.70-5.47; P =
      0.003), more than 1 guide-wire insertions in the pancreatic duct (OR, 5.00; 95%
      CI, 1.97-12.81; P = 0.001) and bile duct stone extraction (OR, 0.12; CI, 0.05
      0.32; P < 0.001). CONCLUSIONS: Pancreatitis potentially associated drugs used
      before ERCP seem to increase the risk for PEP.

PMID- 23548879
TI  - A phase II trial of human secretin infusion for refractory type B pain in chronic
      pancreatitis.
AB  - OBJECTIVE: We aimed to determine if intravenous synthetic human secretin (sHS)
      improves refractory type B pain in patients with chronic pancreatitis (CP).
      METHODS: In a phase II dose escalation trial, patients with CP received sHS of
      varying doses (0.05-0.8 ug/kg) for 3 days. The primary outcomes were changes in
      the visual analogue pain score (VAS), short form (SF)-36, and opiate use from
      baseline at 30 days after infusion. RESULTS: Twelve patients (mean age, 42 years,
      6 men) were included. Mean pain scores (VAS) were 5.79, 4.80, 4.72, and 4.90, at
      baseline, day 4, day 10, and day 30, respectively (P = 0.25, 0.19, and 0.27 when
      compared with baseline, respectively). Daily opiate use (oral morphine
      equivalents) decreased throughout the study from a baseline value of 136 to 111
      mg on day 4 (P = 0.52) and to 104 mg on day 30 (P = 0.34). In subgroup analysis,
      women had the most improvement (VAS baseline, 5.42 vs. VAS day 30, 3.67; P =
      0.07; baseline morphine equivalents, 107 mg vs. 84 mg; P = 0.21). CONCLUSIONS: In
      patients, especially women, with refractory type B pain from CP, intravenous sHS
      administration demonstrated a trend toward improvement in self-reported pain and
      opiate use at 30 days after infusion, although statistical significance was not
      achieved (clinicaltrials.gov registration number NCT01265875).

PMID- 23548880
TI  - Endoscopic ultrasound-guided pancreatic fiducial placement: how important is
      ideal fiducial geometry?
AB  - OBJECTIVE: Image-guided radiation therapy allows precise tumor targeting using
      real-time tracking of radiopaque fiducial markers. To enable appropriate
      tracking, it is recommended to place fiducials with "ideal fiducial geometry"
      (IFG). Our objectives were to determine the proportion of patients in whom IFG
      can be achieved when fiducials are placed by endoscopic ultrasound (EUS) and
      surgery and to determine if attaining IFG is necessary for delivering radiation.
      METHODS: This single-center retrospective cohort study included 77 patients with
      biopsy-proven advanced pancreatic cancer who underwent either EUS-guided or
      laparotomy/laparoscopy-assisted fiducial placement between September 2005 and
      July 2009. RESULTS: Gold fiducials were implanted by EUS in 39 patients (51%) and
      by surgery in 38 patients (49%). The proportion of patients with IFG was
      significantly higher for surgical placement [18/38, 47%; 95% confidence interval
      (CI), 32%-63%] compared with EUS-guided placement (7/39, 18%; 95% CI, 8%-32%), P
      = 0.0011. However, fiducial tracking was successfully used for Cyberknife therapy
      in 35 (90%) of 39 (95% CI, 77%-97%) patients in the EUS group compared with 31
      (82%) of 38 (95% CI, 67%-92%) patients in the surgery group. There were 5
      procedure-related complications in the EUS group. CONCLUSIONS: Achieving IFG
      appears unnecessary for successful tracking and delivery of radiation.

PMID- 23548882
TI  - Delusion of pregnancy: a case revisited.
AB  - A patient with delusion of pregnancy as an early feature of frontotemporal
      dementia with motor neurone disease (FTD/MND) who was reported some years ago was
      posthumously found to harbor the C9ORF72 hexanucleotide repeat expansion, now
      known to be the most common genetic cause of FTD/MND. Some series have found
      psychosis to be common in FTD associated with this mutation, so this test should
      be considered in individuals with clinical features of FTD and MND and/or with a
      family history of either disorder who present with bizarre delusions. 

PMID- 23548883
TI  - Topiramate for abnormal eating behaviour in frontotemporal dementia.
AB  - Topiramate is a sulfamate-substituted monosaccharide anticonvulsant that is
      associated with anorexia and weight loss and has been used to treat binge eating
      disorder and bulimia nervosa. This report describes a man with frontotemporal
      dementia, behavioural variant, associated with abnormal eating behaviour which
      appeared to respond to topiramate. We review the physiological basis of abnormal
      eating behaviour in frontotemporal dementia and explore possible mechanisms of
      action by which topiramate may modify eating behaviour in this condition. 

PMID- 23548884
TI  - Patterns of cognitive dysfunction in progressive MS.
AB  - BACKGROUND: Progressive MS is associated with a high frequency of cognitive
      impairment. However, it is not clear to what extent this reflects global
      dysfunction, or independent deficits in specific functions. OBJECTIVE: To
      characterise patterns of cognitive impairment in progressive MS on a multi
      dimensional cognitive assessment tool well established in neurodegenerative
      diseases. METHODS: Patients with secondary (SPMS; n=60) and primary progressive
      MS (PPMS; n=28) were assessed using the Addenbrooke's Cognitive Examination
      Revised (ACE-R) multi-dimensional cognitive assessment scale. Independent
      dimensions of impairment and their relative contribution to the overall burden of
      cognitive dysfunction were then determined by factor analysis. RESULTS: Two
      independent dimensions of impairment were seen: frontal-executive (attention,
      verbal fluency, recall) on one hand, and language and visuospatial functions on
      the other. These accounted for 55% and 45% respectively of the variance not
      explained by a global influence (14.2% and 11.6% respectively of total variance).
      Isolated language and visuospatial dysfunction was seen in both groups, whereas
      isolated impairment in frontal-executive functions was underrepresented in SPMS
      (p=0.001) and not seen in PPMS patients (p=0.040). CONCLUSIONS: In addition to a
      prominent global influence on cognitive performance, patients with progressive MS
      commonly exhibit language and visuospatial deficits. Evaluation of these
      abilities should therefore be included in clinical assessment of cognition in
      progressive MS.

PMID- 23548885
TI  - Parameters associated with chronic spontaneous urticaria duration and severity: a
      systematic review.
AB  - BACKGROUND: Although some authors have already evaluated the predictive value of
      various parameters regarding the duration of chronic spontaneous urticaria (CSU),
      it remains uncertain which ones have importance in clinical practice as
      prognostic factors that indeed enable prediction. Similarly, some authors have
      investigated parameters that might be related to severe cases of CSU. However,
      the results of studies evaluating several parameters as markers of disease
      severity are fragmented. Thus, we performed a systematic review to summarize the
      findings of studies investigating the parameters associated with CSU duration and
      severity. METHODS: Two authors independently searched PubMed until June 2012 for
      observational retrospective or prospective studies addressing clinical or
      laboratory parameters associated with disease duration or severity in CSU
      patients. RESULTS: We found 1,136 potentially relevant published papers related
      to the subject, 34 of which were included in the systematic review. A total of
      16, 6 and 12 articles evaluated CSU parameters on severity, duration or both,
      respectively. CONCLUSIONS: Our findings suggest that disease severity might
      predict CSU duration. Similarly, evidence suggests that plasma levels of
      prothrombin fragment 1 + 2, D-dimer and C-reactive protein may function as
      markers of CSU severity.

PMID- 23548886
TI  - What's new in the benefits of restoring primary teeth?

PMID- 23548887
TI  - Topical retinoids in oral lichen planus treatment: an overview.
AB  - BACKGROUND: Treatment of oral lichen planus (OLP) is a major challenge for
      clinicians and patients. There is limited scientific evidence about topical
      treatment with retinoids. We conducted a literature review of data on the
      effectiveness and safety of topical retinoids in OLP patients. MATERIALS AND
      METHODS: We searched the MEDLINE, Embase and Cochrane databases for articles on
      topical retinoids treatment on OLP patients (searches from 1970 to February
      2012). RESULTS: Sixteen studies (280 OLP patients topically treated with
      different classes of retinoids) met the inclusion criteria. Isotretinoin was the
      most frequently employed retinoid in the treatment of OLP. The clinical and/or
      histopathological efficacy of retinoids was recorded in the majority of the
      selected studies. A transient and moderate burning sensation was the most
      frequently reported side effect. CONCLUSIONS: Topical retinoids appear as an
      alternative choice in OLP treatment. Whether keratotic OLP better responds to
      topical retinoids than erosive OLP is still an open question that deserves
      further comparative and controlled clinical trials. The benefits and harms of
      using topical retinoids in people with OLP require thorough evaluation in
      properly designed controlled studies.

PMID- 23548888
TI  - Use of multidetector computed tomography to guide management of pneumothorax.
AB  - PURPOSE OF REVIEW: Pneumothorax, a potentially life-threatening condition, is
      present in about one-third of chest trauma patients. Traditionally, pneumothorax
      has been diagnosed and managed by use of chest radiography, which has been found
      inaccurate and inconsistent. With the ubiquitous application of multidetector
      computed tomography (MDCT) in emergency care, MDCT quantification of
      pneumothoraces becomes an emerging technique for accurate determination of the
      size of pneumothoraces. The use of MDCT quantification provides a promising means
      to improve pneumothorax management. RECENT FINDINGS: Recent studies have
      demonstrated that MDCT is the gold standard for detecting pneumothorax and MDCT
      provides an effective imaging modality for the accurate measurement of the volume
      of pneumothoraces. The use of MDCT volumetric quantification of pneumothoraces
      has been evidenced in the improvement of performance in pneumothorax management
      for clinically stable chest trauma patients. SUMMARY: The MDCT volumetric
      quantification of pneumothoraces is a new concept in the care of chest trauma
      patients and has the potential to improve pneumothorax management. Further
      clinical studies are needed to establish a MDCT-based clinical guideline for
      pneumothorax management.

PMID- 23548889
TI  - Access to chemical data: Lutter et al. respond.

PMID- 23548890
TI  - Waiting for platelet counts causes unsubstantiated delay of thrombolysis therapy.
AB  - BACKGROUND: Platelet counts (PCs) <100,000/ul are considered as a
      contraindication for intravenous thrombolysis (IVT). While US guidelines
      recommend IVT initiation before the availability of clotting tests, the
      guidelines of the European Stroke Organization give no such practical advice. We
      aimed to assess the incidence of thrombocytopenia in IVT patients, outcome after
      thrombolysis in affected patients and the time gained by initiating treatment
      prior to availability of PC results. METHODS: All patients with thrombocytopenia
      were identified in our prospectively acquired thrombolysis database. Baseline
      demographic data, intracerebral hemorrhage rates as well as functional outcome
      were assessed. The median time between initiation of thrombolysis and
      availability of PCs was calculated. RESULTS: Of 625 IVT patients, 3 (0.5%) had
      thrombocytopenia at stroke onset. None of them developed intracerebral hemorrhage
      (ICH) or died during the follow-up. Waiting for PCs would have delayed treatment
      in 72.4% of the patients, with a median hypothetical delay of 22 min
      (interquartile range: 11-41 min). CONCLUSIONS: To date, there are no sufficient
      data to evaluate the ICH risk in thrombocytopenic patients. However,
      thrombocytopenia is rare in IVT patients. Thus, generally waiting for PC results
      prior to initiation of IVT is not warranted. Avoiding this significant delay
      yields shorter door-to-needle times and potentially more effective treatment.

PMID- 23548892
TI  - [The influence of culture in the oral expression of pain: comparative study
      between French and Syrian cancer patients].
AB  - This study examines the role of culture in the perception and the verbal
      expression of pain among syrian and french blood-related cancer patients. The
      level of intensity (AVS scale) and the different aspects (Saint-Antoine Pain
      Questionnaire [SAPQ]) of their pain were studied. The sensory and emotional
      descriptors chosen by the Syrian possessed a stronger semantic content in
      comparison to those used by the French. The patient's cultural background, which
      affect the perception and verbal expression of pain should be a new indicator in
      the optimization of global medical management.

PMID- 23548893
TI  - Sclerotic effect of bleomycin on the submandibular gland: an experimental model.
AB  - OBJECTIVES: To evaluate the sclerotic effect of bleomycin on the submandibular
      gland histopathologically and assess it as a possible alternative therapy for
      sialorrhea. METHODS: An experimental model was designed and 18 New Zealand white
      rabbits were used. The rabbits were divided into two groups: a bleomycin group
      (n=9) and a sham group (n=9). The submandibular glands of the bleomycin group
      were injected with 0.3 ml bleomycin (3mg/ml) while the sham group received 0.3 ml
      saline. Four weeks after the procedure, the glands were removed.
      Histopathological studies including hematoxylin-eosin and Masson's trichrome
      stain were carried out. The glands were evaluated for tissue inflammation,
      fibrosis, edema, lipomatosis, atrophy and congestion. To investigate apoptosis,
      terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-11-dUTP nick-end
      labeling (TUNEL) immunohistochemical staining was used. RESULTS: In the group
      injected with bleomycin, inflammation (n=8), edema (n=4), fibrosis (n=3),
      congestion (n=4) and lipomatosis (n=7) were observed. In the sham group, only
      lipomatosis was observed. The TUNEL assay results were 5.06 +/- 1.18 (p<0.05) for
      acinar cells and 8.46 +/- 0.82 (p<0.05) for ductal cells in the bleomycin group.
      This was significantly different from the results in the sham group. CONCLUSIONS:
      Apoptosis, inflammation, fibrosis, edema, lipomatosis and congestion were
      observed in the ductal and acinar cells of the bleomycin group. Bleomycin may be
      an alternative treatment for sialorrhea cases. However, more research is needed.

PMID- 23548894
TI  - Primary endobronchial Burkitt's lymphoma in a child: a case report.
AB  - Primary endobronchial tumors are rare in children and often are misdiagnosed,
      resulting in a delay of appropriate treatment. Here, we present a case of 4-year
      old girl with primary endobronchial lymphoma who presented with persistent
      pneumonia despite medical treatment. Her chest radiograph showed left
      atelectasis, and a bronchial foreign body was initially suspected. Bronchoscopic
      examination demonstrated a granulomatous tumor occupying the left main bronchus.
      Localized Burkitt's lymphoma in the left trachea was diagnosed
      histopathologically. This case emphasizes the consideration of endobronchial
      tumor and bronchoscopy in children who show persistent atelectasis or recurrent
      pneumonia.

PMID- 23548895
TI  - Obesity as a showcase for transdisciplinary research.
AB  - Obesity is one of the main health problems in the world with high societal and
      individual costs. To tackle the obesity epidemic, we need to collaborate across
      scientific boarders to fundamentally broaden the perspectives on the obesity
      epidemic as a complex phenomenon.

PMID- 23548891
TI  - Categorization = decision making + generalization.
AB  - We rarely, if ever, repeatedly encounter exactly the same situation. This makes
      generalization crucial for real world decision making. We argue that
      categorization, the study of generalizable representations, is a type of decision
      making, and that categorization learning research would benefit from approaches
      developed to study the neuroscience of decision making. Similarly, methods
      developed to examine generalization and learning within the field of
      categorization may enhance decision making research. We first discuss perceptual
      information processing and integration, with an emphasis on accumulator models.
      We then examine learning the value of different decision making choices via
      experience, emphasizing reinforcement learning modeling approaches. Next we
      discuss how value is combined with other factors in decision making, emphasizing
      the effects of uncertainty. Finally, we describe how a final decision is selected
      via thresholding processes implemented by the basal ganglia and related regions.
      We also consider how memory related functions in the hippocampus may be
      integrated with decision making mechanisms and contribute to categorization. 

PMID- 23548896
TI  - Identification of a new interaction mode between the Src homology 2 domain of C
      terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with
      glycosphingolipid microdomains.
AB  - Proteins with Src homology 2 (SH2) domains play major roles in tyrosine kinase
      signaling. Structures of many SH2 domains have been studied, and the regions
      involved in their interactions with ligands have been elucidated. However, these
      analyses have been performed using short peptides consisting of phosphotyrosine
      followed by a few amino acids, which are described as the canonical recognition
      sites. Here, we report the solution structure of the SH2 domain of C-terminal Src
      kinase (Csk) in complex with a longer phosphopeptide from the Csk-binding protein
      (Cbp). This structure, together with biochemical experiments, revealed the
      existence of a novel binding region in addition to the canonical phosphotyrosine
      314-binding site of Cbp. Mutational analysis of this second region in cells
      showed that both canonical and novel binding sites are required for tumor
      suppression through the Cbp-Csk interaction. Furthermore, the data indicate an
      allosteric connection between Cbp binding and Csk activation that arises from
      residues in the betaB/betaC loop of the SH2 domain.

PMID- 23548897
TI  - G-protein-coupled receptor agonist BV8/prokineticin-2 and STAT3 protein form a
      feed-forward loop in both normal and malignant myeloid cells.
AB  - BACKGROUND: Signaling pathways underlying BV8-mediated oncogenesis remain
      unknown. RESULTS: BV8-STAT3 forms a feed-forward loop in both normal and
      malignant myeloid cells and promotes tumor growth. CONCLUSION: JAK2/STAT3
      signaling plays critical roles in BV8-mediated myeloid cell-dependent
      oncogenesis. SIGNIFICANCE: This study identifies a novel role of BV8-STAT3
      signaling in mediating cross-talk between tumor microenvironment and tumor cells.
      An important role of BV8 in mobilization of myeloid cells and myeloid cell
      dependent angiogenesis has been established. Recently, it has also been shown
      that granulocyte colony-stimulating factor (G-CSF)-induced BV8 expression is
      STAT3 dependent in CD11b(+)Gr1(+) myeloid cells. However, the BV8 downstream
      signaling pathway(s) intrinsic to myeloid cells crucial for angiogenesis, and
      potentially also for development of cancers of myeloid origin, remains largely
      unknown. Here we show that BV8 activates STAT3, which is critical for regulating
      genes important for both tumor cell proliferation/survival and tumor
      angiogenesis, in both normal and malignant myeloid cells. Further, BV8-induced
      STAT3 activation requires Janus-activated kinase 2 (JAK2) activity as shown by
      both genetic and pharmacologic inhibition. Knocking down BV8 in human myeloid
      leukemia cells inhibits STAT3 activity and expression of STAT3 downstream
      angiogenic and pro-proliferation/survival genes, leading to a decrease in tumor
      cell viability. BV8 shRNA expressing leukemia cells exhibit reduced STAT3
      activity and tumor growth in vivo. Taken together, we have delineated a signaling
      pathway downstream of BV8 that plays critical roles in both the tumor
      microenvironment and malignant myeloid cells for angiogenesis and tumor cell
      proliferation/survival.

PMID- 23548898
TI  - Systematic analysis of gamma-aminobutyric acid (GABA) metabolism and function in
      the social amoeba Dictyostelium discoideum.
AB  - While GABA has been suggested to regulate spore encapsulation in the social
      amoeba Dictyostelium discoideum, the metabolic profile and other potential
      functions of GABA during development remain unclear. In this study, we
      investigated the homeostasis of GABA metabolism by disrupting genes related to
      GABA metabolism and signaling. Extracellular levels of GABA are tightly regulated
      during early development, and GABA is generated by the glutamate decarboxylase,
      GadB, during growth and in early development. However, overexpression of the
      prespore-specific homologue, GadA, in the presence of GadB reduces production of
      extracellular GABA. Perturbation of extracellular GABA levels delays the process
      of aggregation. Cytosolic GABA is degraded by the GABA transaminase, GabT, in the
      mitochondria. Disruption of a putative vesicular GABA transporter (vGAT)
      homologue DdvGAT reduces secreted GABA. We identified the GABAB receptor-like
      family member GrlB as the major GABA receptor during early development, and
      either disruption or overexpression of GrlB delays aggregation. This delay is
      likely the result of an abolished pre-starvation response and late expression of
      several "early" developmental genes. Distinct genes are employed for GABA
      generation during sporulation. During sporulation, GadA alone is required for
      generating GABA and DdvGAT is likely responsible for GABA secretion. GrlE but not
      GrlB is the GABA receptor during late development.

PMID- 23548899
TI  - CD14 protein acts as an adaptor molecule for the immune recognition of Salmonella
      curli fibers.
AB  - Amyloids, protein aggregates with a cross beta-sheet structure, contribute to
      inflammation in debilitating disorders, including Alzheimer's disease. Enteric
      bacteria also produce amyloids, termed curli, contributing to inflammation during
      infection. It has been demonstrated that curli and beta-amyloid are recognized by
      the immune system via the Toll-like receptor (TLR) 2/TLR1 complex. Here we
      investigated the role of CD14 in the immune recognition of bacterial amyloids. We
      used HeLa 57A cells, a human cervical cancer cell line containing a luciferase
      reporter gene under the control of an NF-kappaB promoter. When HeLa 57A cells
      were transiently transfected with combinations of human expression vectors
      containing genes for TLR2, TLR1, and CD14, membrane-bound CD14 enhanced NF-kappaB
      activation through the TLR2/TLR1 complex stimulated with curli fibers or
      recombinant CsgA, the curli major subunit. Similarly, soluble CD14 augmented the
      TLR2/TLR1 response to curli fibers in the absence of membrane-bound CD14. We
      further revealed that IL-6 and nitric oxide production were significantly higher
      by wild-type (C57BL/6) bone marrow-derived macrophages compared with TLR2
      deficient or CD14-deficient bone marrow-derived macrophages when stimulated with
      curli fibers, recombinant CsgA, or synthetic CsgA peptide, CsgA-R4-5. Binding
      assays demonstrated that recombinant TLR2, TLR1, and CD14 bound purified curli
      fibers. Interestingly, CD14-curli interaction was specific to the fibrillar form
      of the amyloid, as demonstrated by using synthetic CsgA peptides proficient and
      deficient in fiber formation, respectively. Activation of the TLR2/TLR1/CD14
      trimolecular complex by amyloids provides novel insights for innate immunity with
      implications for amyloid-associated diseases.

PMID- 23548900
TI  - Endomembrane H-Ras controls vascular endothelial growth factor-induced nitric
      oxide synthase-mediated endothelial cell migration.
AB  - We demonstrate for the first time that endomembrane-delimited H-Ras mediates VEGF
      induced activation of endothelial nitric-oxide synthase (eNOS) and migratory
      response of human endothelial cells. Using thiol labeling strategies and
      immunofluorescent cell staining, we found that only 31% of total H-Ras is S
      palmitoylated, tethering the small GTPase to the plasma membrane but leaving the
      function of the large majority of endomembrane-localized H-Ras unexplained.
      Knockdown of H-Ras blocked VEGF-induced PI3K-dependent Akt (Ser-473) and eNOS
      (Ser-1177) phosphorylation and nitric oxide-dependent cell migration,
      demonstrating the essential role of H-Ras. Activation of endogenous H-Ras led to
      recruitment and phosphorylation of eNOS at endomembranes. The loss of migratory
      response in cells lacking endogenous H-Ras was fully restored by modest
      overexpression of an endomembrane-delimited H-Ras palmitoylation mutant. These
      studies define a newly recognized role for endomembrane-localized H-Ras in
      mediating nitric oxide-dependent proangiogenic signaling.

PMID- 23548901
TI  - Phosphorylation drives an apoptotic protein to activate antiapoptotic genes:
      paradigm of influenza A matrix 1 protein function.
AB  - During infection, viral proteins target cellular pathways that regulate cellular
      innate immune responses and cell death. We demonstrate that influenza A virus
      matrix 1 protein (M1), an established proapoptotic protein, activates nuclear
      factor-kappaB member RelB-mediated survival genes (cIAP1, cIAP2, and cFLIP), a
      function that is linked with its nuclear translocation during early infection.
      Death domain-associated protein 6 (Daxx) is a transcription co-repressor of the
      RelB-responsive gene promoters. During influenza virus infection M1 binds to and
      stabilizes Daxx protein by preventing its ubiquitination and proteasomal
      degradation. Binding of M1 with Daxx through its Daxx binding motif prevents
      binding of RelB and Daxx, resulting in up-regulation of survival genes. This
      interaction also prevents promoter recruitment of DNA methyltransferases (Dnmt1
      and Dnmt3a) and lowers CpG methylation of the survival gene promoters, leading to
      the activation of these genes. Thus, M1 prevents repressional function of Daxx
      during infection, thereby exerting a survival role. In addition to its nuclear
      localization signal, translocation of M1 to the nucleus depends on cellular
      kinase-mediated phosphorylation as the protein kinase C inhibitor calphostin C
      effectively down-regulates virus replication. The study reconciles the ambiguity
      of dual antagonistic function of viral protein and potentiates a possible target
      to limit virus infection.

PMID- 23548902
TI  - Norepinephrine modulates the motility of resting and activated microglia via
      different adrenergic receptors.
AB  - Microglia, the resident immune cells of the central nervous system (CNS), monitor
      the brain for disturbances of tissue homeostasis by constantly moving their fine
      processes. Microglia respond to tissue damage through activation of ATP/ADP
      receptors followed by directional process extension to the damaged area. A common
      feature of several neurodegenerative diseases is the loss of norepinephrine,
      which might contribute to the associated neuroinflammation. We carried out a high
      resolution analysis of the effects of norepinephrine (NE) on microglial process
      dynamics in acute brain slices from mice that exhibit microglia-specific enhanced
      green fluorescent protein expression. Bath application of NE to the slices
      resulted in significant process retraction in microglia. Analysis of adrenergic
      receptor expression with quantitative PCR indicated that resting microglia
      primarily express beta2 receptors but switch expression to alpha2A receptors
      under proinflammatory conditions modeled by LPS treatment. Despite the
      differential receptor expression, NE caused process retraction in both resting
      and LPS-activated microglia cultured in the gelatinous substrate Matrigel in
      vitro. The use of subtype-selective receptor agonists and antagonists confirmed
      the involvement of beta2 receptors in mediating microglial process dynamics in
      resting cells and alpha2A receptors in activated cells. Co-application of NE with
      ATP to resting microglia blocked the ATP-induced process extension and migration
      in isolated microglia, and beta2 receptor antagonists prolonged ATP effects in
      brain slice tissues, suggesting the presence of cross-talk between adrenergic and
      purinergic signaling in microglia. These data show that the neurotransmitter NE
      can modulate microglial motility, which could affect microglial functions in
      pathogenic situations of either elevated or reduced NE levels.

PMID- 23548903
TI  - Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase
      mediated generation of 5-hydroxymethylcytosine.
AB  - BACKGROUND: Tet methylcytosine dioxygenase converts 5-mC to 5-hmC in DNA.
      RESULTS: Ascorbate significantly and specifically enhances Tet-mediated
      generation of 5-hmC. CONCLUSION: Our findings suggest that ascorbate enhances 5
      hmC generation, most likely by acting as a co-factor for Tet methylcytosine
      dioxygenase to generate 5-hmC. SIGNIFICANCE: The availability of ascorbate could
      have significant consequences for health and diseases by modulating the
      epigenetic control of genome activity. Ascorbate (vitamin C) is best known for
      its role in scurvy, in which the hydroxylation of collagen catalyzed by
      dioxygenases is incomplete due to ascorbate deficiency. Here, we report a novel
      function of ascorbate in the hydroxylation of 5-methylcytosine (5-mC) to 5
      hydroxymethylcytosine (5-hmC) in DNA catalyzed by Tet (ten-eleven translocation)
      methylcytosine dioxygenase. The content of 5-hmC is extremely low in mouse
      embryonic fibroblasts cultured in ascorbate-free medium. Additions of ascorbate
      dose- and time-dependently enhance the generation of 5-hmC, without any effects
      on the expression of Tet genes. Treatment with another reducer glutathione (GSH)
      does not change the level of 5-hmC. Further, blocking ascorbate entry into cells
      by phloretin and knocking down Tet (Tet1, Tet2, and Tet3) expression by short
      interference RNAs (siRNA) significantly inhibit the effect of ascorbate on 5-hmC.
      These results suggest that ascorbate enhances 5-hmC generation, most likely by
      acting as a co-factor for Tet methylcytosine dioxygenase to hydroxylate 5-mC.
      Thus, we have uncovered a novel role for ascorbate in modulating the epigenetic
      control of genome activity.

PMID- 23548904
TI  - Phenformin activates the unfolded protein response in an AMP-activated protein
      kinase (AMPK)-dependent manner.
AB  - BACKGROUND: The cross-talk between UPR activation and metabolic stress remains
      largely unclear. RESULTS: Phenformin treatment activates the IRE1alpha and PERK
      pathways in an AMPK-dependent manner. CONCLUSION: AMPK is required for phenformin
      mediated IRE1alpha and PERK activation. SIGNIFICANCE: Our findings demonstrate
      the cross-talk between UPR and metabolic signals. Activation of the unfolded
      protein response (UPR) is associated with the disruption of endoplasmic reticulum
      (ER) homeostasis and has been implicated in the pathogenesis of many human
      metabolic diseases, including obesity and type 2 diabetes. However, the nature of
      the signals activating UPR under these conditions remains largely unknown. Using
      a method that we recently optimized to directly measure UPR sensor activation, we
      screened the effect of various metabolic drugs on UPR activation and show that
      the anti-diabetic drug phenformin activates UPR sensors IRE1alpha and pancreatic
      endoplasmic reticulum kinase (PERK) in both an ER-dependent and ER-independent
      manner. Mechanistically, AMP-activated protein kinase (AMPK) activation is
      required but not sufficient to initiate phenformin-mediated IRE1alpha and PERK
      activation, suggesting the involvement of additional factor(s). Interestingly,
      activation of the IRE1alpha (but not PERK) pathway is partially responsible for
      the cytotoxic effect of phenformin. Together, our data show the existence of a
      non-canonical UPR whose activation requires the cytosolic kinase AMPK, adding
      another layer of complexity to UPR activation upon metabolic stress.

PMID- 23548905
TI  - Competition between core-2 GlcNAc-transferase and ST6GalNAc-transferase regulates
      the synthesis of the leukocyte selectin ligand on human P-selectin glycoprotein
      ligand-1.
AB  - The binding of selectins to carbohydrate ligands expressed on leukocytes
      regulates immunity and inflammation. Among the human selectin ligands, the O
      linked glycans at the N-terminus of the leukocyte cell-surface molecule P
      selectin glycoprotein ligand-1 (PSGL-1, CD162) are important because they bind
      all selectins (L-, E-, and P-selectin) with high affinity under hydrodynamic
      shear conditions. Analysis of glycan microheterogeneity at this site is
      complicated by the presence of 72 additional potential O-linked glycosylation
      sites on this mucinous protein. To overcome this limitation, truncated forms of
      PSGL-1, called "PSGL-1 peptide probes," were developed. Ultra-high sensitivity
      mass spectrometry analysis of glycans released from such probes along with
      glycoproteomic analysis demonstrate the presence of both the sialyl Lewis-X
      (sLe(X)) and the di-sialylated T-antigen
      (NeuAcalpha2,3Galbeta1,3(NeuAcalpha2,6)GalNAc) at the PSGL-1 N-terminus.
      Overexpression of glycoprotein-specific ST6GalNAc-transferases (ST6GalNAc1, -2,
      or -4) in human promyelocytic HL-60 cells altered glycan structures and cell
      adhesion properties. In particular, ST6GalNAc2 overexpression abrogated cell
      surface HECA-452/CLA expression, reduced the number of rolling leukocytes on P-
      and L-selectin-bearing substrates by ~85%, and increased median rolling velocity
      of remaining cells by 80-150%. Cell rolling on E-selectin was unaltered although
      the number of adherent cells was reduced by 60%. ST6GalNAc2 partially co
      localizes in the Golgi with the core-2 beta(1,6)GlcNAc-transferase C2GnT-1.
      Overall, the data describe the glycan microheterogeneity at the PSGL-1 N
      terminus. They suggest that a competition between ST6GalNAc2 and C2GnT-1 for the
      core-1/Galbeta1,3GalNAc glycan may regulate leukocyte adhesion under fluid shear.

PMID- 23548906
TI  - Epigallocatechin gallate targeting of membrane type 1 matrix metalloproteinase
      mediated Src and Janus kinase/signal transducers and activators of transcription
      3 signaling inhibits transcription of colony-stimulating factors 2 and 3 in
      mesenchymal stromal cells.
AB  - BACKGROUND: CSF-2 and CSF-3 confer proangiogenic and immunomodulatory properties
      to mesenchymal stromal cells (MSCs). RESULTS: Transcriptional regulation of CSF-2
      and CSF-3 in concanavalin A-activated MSCs requires MT1-MMP signaling and is
      inhibited by EGCG. CONCLUSION: The chemopreventive properties of diet-derived
      EGCG alter MT1-MMP-mediated intracellular signaling. SIGNIFICANCE:
      Pharmacological targeting of MSCs proangiogenic functions may prevent their
      contribution to tumor development. Epigallocatechin gallate (EGCG), a major form
      of tea catechins, possesses immunomodulatory and antiangiogenic effects, both of
      which contribute to its chemopreventive properties. In this study, we evaluated
      the impact of EGCG treatment on the expression of colony-stimulating factors
      (CSF) secreted from human bone marrow-derived mesenchymal stromal cells (MSCs),
      all of which also contribute to the immunomodulatory and angiogenic properties of
      these cells. MSCs were activated with concanavalin A (ConA), a Toll-like receptor
      (TLR)-2 and TLR-6 agonist as well as a membrane type 1 matrix metalloproteinase
      (MT1-MMP) inducer, which increased granulocyte macrophage-CSF (GM-CSF, CSF-2),
      granulocyte CSF (G-CSF, CSF-3), and MT1-MMP gene expression. EGCG antagonized the
      ConA-induced CSF-2 and CSF-3 gene expression, and this process required an MT1
      MMP-mediated sequential activation of the Src and JAK/STAT pathways. Gene
      silencing of MT1-MMP expression further demonstrated its requirement in the
      phosphorylation of Src and STAT3, whereas overexpression of a nonphosphorylatable
      MT1-MMP mutant (Y573F) abrogated CSF-2 and CSF-3 transcriptional increases. Given
      that MSCs are recruited within vascularizing tumors and are believed to
      contribute to tumor angiogenesis, possibly through secretion of CSF-2 and CSF-3,
      our study suggests that diet-derived polyphenols such as EGCG may exert
      chemopreventive action through pharmacological targeting of the MT1-MMP
      intracellular signaling.

PMID- 23548907
TI  - High-affinity cyclic peptide matriptase inhibitors.
AB  - BACKGROUND: Sunflower trypsin inhibitor-1 (SFTI-1) and Momordica cochinchinensis
      trypsin inhibitor-II (MCoTI-II) are potent protease inhibitors comprising a
      cyclic backbone. RESULTS: Elucidation of structure-activity relationships for
      SFTI-1 and MCoTI-II was used to design inhibitors with enhanced inhibitory
      activity. CONCLUSION: An analog of MCoTI-II is one of the most potent inhibitors
      of matriptase. SIGNIFICANCE: These results provide a solid basis for the design
      of selective peptide inhibitors of matriptase with therapeutic potential. The
      type II transmembrane serine protease matriptase is a key activator of multiple
      signaling pathways associated with cell proliferation and modification of the
      extracellular matrix. Deregulated matriptase activity correlates with a number of
      diseases, including cancer and hence highly selective matriptase inhibitors may
      have therapeutic potential. The plant-derived cyclic peptide, sunflower trypsin
      inhibitor-1 (SFTI-1), is a promising drug scaffold with potent matriptase
      inhibitory activity. In the current study we have analyzed the structure-activity
      relationships of SFTI-1 and Momordica cochinchinensis trypsin inhibitor-II (MCoTI
      II), a structurally divergent trypsin inhibitor from Momordica cochinchinensis
      that also contains a cyclic backbone. We show that MCoTI-II is a significantly
      more potent matriptase inhibitor than SFTI-1 and that all alanine mutants of both
      peptides, generated using positional scanning mutagenesis, have decreased trypsin
      affinity, whereas several mutations either maintain or result in enhanced
      matriptase inhibitory activity. These intriguing results were used to design one
      of the most potent matriptase inhibitors known to date with a 290 pm equilibrium
      dissociation constant, and provide the first indication on how to modulate
      affinity for matriptase over trypsin in cyclic peptides. This information might
      be useful for the design of more selective and therapeutically relevant
      inhibitors of matriptase.

PMID- 23548908
TI  - Inhibition of isoleucyl-tRNA synthetase as a potential treatment for human
      African Trypanosomiasis.
AB  - Trypanosoma brucei sp. causes human African trypanosomiasis (HAT; African
      sleeping sickness). The parasites initially proliferate in the hemolymphatic
      system and then invade the central nervous system, which is lethal if not
      treated. New drugs are needed for HAT because the approved drugs are few, toxic,
      and difficult to administer, and drug resistance is spreading. We showed by RNAi
      knockdown that T. brucei isoleucyl-tRNA synthetase is essential for the parasites
      in vitro and in vivo in a mouse model of infection. By structure prediction and
      experimental analysis, we also identified small molecules that inhibit
      recombinant isoleucyl-tRNA synthetase and that are lethal to the parasites in
      vitro and highly selective compared with mammalian cells. One of these molecules
      acts as a competitive inhibitor of the enzyme and cures mice of the infection.
      Because members of this class of molecules are known to cross the blood-brain
      barrier in humans and to be tolerated, they may be attractive as leading
      candidates for drug development for HAT.

PMID- 23548909
TI  - Angiotensin II impairs endothelial nitric-oxide synthase bioavailability under
      free cholesterol-enriched conditions via intracellular free cholesterol-rich
      membrane microdomains.
AB  - Vascular endothelial function is impaired in hypercholesterolemia partly because
      of injury by modified LDL. In addition to modified LDL, free cholesterol (FC) is
      thought to play an important role in the development of endothelial dysfunction,
      although the precise mechanisms remain to be elucidated. The aim of this study
      was to clarify the mechanisms of endothelial dysfunction induced by an FC-rich
      environment. Loading cultured human aortic endothelial cells with FC induced the
      formation of vesicular structures composed of FC-rich membranes. Raft proteins
      such as phospho-caveolin-1 (Tyr-14) and small GTPase Rac were accumulated toward
      FC-rich membranes around vesicular structures. In the presence of these vesicles,
      angiotensin II-induced production of reactive oxygen species (ROS) was
      considerably enhanced. This ROS shifted endothelial NOS (eNOS) toward vesicle
      membranes and vesicles with a FC-rich domain trafficked toward perinuclear late
      endosomes/lysosomes, which resulted in the deterioration of eNOS Ser-1177
      phosphorylation and NO production. Angiotensin II-induced ROS decreased the
      bioavailability of eNOS under the FC-enriched condition.

PMID- 23548910
TI  - Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in
      mice and promotes lung cancer progression by modulating inflammatory responses.
AB  - Human MMP-1 is a matrix metalloproteinase repeatedly associated with many
      pathological conditions, including cancer. Thus, MMP1 overexpression is a poor
      prognosis marker in a variety of advanced cancers, including colorectal, breast,
      and lung carcinomas. Moreover, MMP-1 plays a key role in the metastatic behavior
      of melanoma, breast, and prostate cancer cells. However, functional and
      mechanistic studies on the relevance of MMP-1 in cancer have been hampered by the
      absence of an in vivo model. In this work, we have generated mice deficient in
      Mmp1a, the murine ortholog of human MMP1. Mmp1a(-/-) mice are viable and fertile
      and do not exhibit obvious abnormalities, which has facilitated studies of cancer
      susceptibility. These studies have shown a decreased susceptibility to develop
      lung carcinomas induced by chemical carcinogens in Mmp1a(-/-) mice.
      Histopathological analysis indicated that tumors generated in Mmp1a(-/-) mice are
      smaller than those of wild-type mice, consistently with the idea that the absence
      of Mmp-1a hampers tumor progression. Proteomic analysis revealed decreased levels
      of chitinase-3-like 3 and accumulation of the receptor for advanced glycation end
      products and its ligand S100A8 in lung samples from Mmp1a(-/-) mice compared with
      those from wild-type. These findings suggest that Mmp-1a could play a role in
      tumor progression by modulating the polarization of a Th1/Th2 inflammatory
      response to chemical carcinogens. On the basis of these results, we propose that
      Mmp1a knock-out mice provide an excellent in vivo model for the functional
      analysis of human MMP-1 in both physiological and pathological conditions.

PMID- 23548911
TI  - Mycobacterium tuberculosis RNA polymerase-binding protein A (RbpA) and its
      interactions with sigma factors.
AB  - RNA polymerase-binding protein A (RbpA), encoded by Rv2050, is specific to the
      actinomycetes, where it is highly conserved. In the pathogen Mycobacterium
      tuberculosis, RbpA is essential for growth and survival. RbpA binds to the beta
      subunit of the RNA polymerase where it activates transcription by unknown
      mechanisms, and it may also influence the response of M. tuberculosis to the
      current frontline anti-tuberculosis drug rifampicin. Here we report the solution
      structure of RbpA and identify the principle sigma factor sigma(A) and the stress
      induced sigma(B) as interaction partners. The protein has a central ordered
      domain with a conserved hydrophobic surface that may be a potential protein
      interaction site. The N and C termini are highly dynamic and are involved in the
      interaction with the sigma factors. RbpA forms a tight complex with the N
      terminal domain of sigma(B) via its N- and C-terminal regions. The interaction
      with sigma factors may explain how RbpA stabilizes sigma subunit binding to the
      core RNA polymerase and thereby promotes initiation complex formation. RbpA could
      therefore influence the competition between principal and alternative sigma
      factors and hence the transcription profile of the cell.

PMID- 23548913
TI  - NeuroAiD: properties for neuroprotection and neurorepair.
AB  - BACKGROUND: Treatments for stroke and other brain injuries are limited. NeuroAiD
      has been shown to be beneficial in clinical studies. We reviewed the
      pharmacological effects of NeuroAiD on the normal and ischemic brain and neurons.
      METHODS: In vivo and in vitro experiments using mouse model of stroke (focal
      ischemia), rat model of cardiac arrest (global ischemia) and cortical neurons in
      culture were reviewed and summarized. RESULTS: NeuroAiD improved survival,
      attenuated infarct size, improved functional recovery in the model of focal
      ischemia, and protected neurons against glutamate-induced injury. Furthermore, it
      enhanced cognitive recovery by reducing hippocampal CA1 cell degeneration, DNA
      fragmentation, Bax expression and ma-londialdehyde release in the model of global
      ischemia. Activation of the Akt survival pathway and opening of KATP channels may
      contribute to the neuroprotective properties of NeuroAiD. NeuroAiD increased BDNF
      expression and induced proliferation of cells which differentiate and mature into
      neurons. It enhanced rosette formation of human embryonic stem cells. NeuroAiD
      treated embryonic cortical neurons developed into neurons with longer neurites,
      denser outgrowths and networks, and more synaptic release sites. CONCLUSIONS:
      NeuroAiD demonstrated both neuroprotective and neuroregenerative properties in
      rodent models of focal and global ischemia and in cortical cell cultures. These
      properties would be important for developing a treatment strategy in reducing the
      long-term disability of stroke, cardiac arrest and other brain injuries.

PMID- 23548912
TI  - Mechanism of ferrous iron binding and oxidation by ferritin from a pennate
      diatom.
AB  - A novel ferritin was recently found in Pseudo-nitzschia multiseries (PmFTN), a
      marine pennate diatom that plays a major role in global primary production and
      carbon sequestration into the deep ocean. Crystals of recombinant PmFTN were
      soaked in iron and zinc solutions, and the structures were solved to 1.65-2.2-A
      resolution. Three distinct iron binding sites were identified as determined from
      anomalous dispersion data from aerobically grown ferrous soaked crystals. Sites A
      and B comprise the conserved ferroxidase active site, and site C forms a pathway
      leading toward the central cavity where iron storage occurs. In contrast, crystal
      structures derived from anaerobically grown and ferrous soaked crystals revealed
      only one ferrous iron in the active site occupying site A. In the presence of
      dioxygen, zinc is observed bound to all three sites. Iron oxidation experiments
      using stopped-flow absorbance spectroscopy revealed an extremely rapid phase
      corresponding to Fe(II) oxidation at the ferroxidase site, which is saturated
      after adding 48 ferrous iron to apo-PmFTN (two ferrous iron per subunit), and a
      much slower phase due to iron core formation. These results suggest an ordered
      stepwise binding of ferrous iron and dioxygen to the ferroxidase site in
      preparation for catalysis and a partial mobilization of iron from the site
      following oxidation.

PMID- 23548914
TI  - Efficacy and safety of MLC601 (NeuroAiD(r)), a traditional Chinese medicine, in
      poststroke recovery: a systematic review.
AB  - BACKGROUND: Subsequent to a pooled analysis of 2 trials, several more studies
      have been published assessing the benefit of MLC601 in stroke patients. Hence, it
      is timely to conduct an updated meta-analysis to frame the interpretation of the
      results of an ongoing large multicenter, randomized, double-blind, placebo
      controlled study. Therefore, we conducted a systematic review of the efficacy of
      MLC601 in improving the recovery of stroke patients. METHODS: PubMed(r) and the
      Cochrane Library(r) databases were searched for trials evaluating MLC601 in
      stroke patients. Primary outcome was functional independence, assessed by the
      Barthel Index or the Diagnostic Therapeutic Effects of Apoplexy scoring system,
      item 8. Secondary outcomes were improvement in functional independence scores,
      motor recovery, reduction in visual field defect and increase in cerebral blood
      flow. Two authors performed the article selection, appraisal and data extraction
      while resolving differences through discussion or consulting a third author. Data
      were analyzed in RevMan5(r). Meta-analysis was conducted using a random effects
      model. RESULTS: This review included 6 studies with overall low risk of bias but
      some clinical heterogeneity. MLC601 increased the chances of achieving functional
      independence after stroke compared to control treatments (risk ratio, 2.35; 95%
      CI, 1.31-4.23). No deaths and 4 serious adverse events were reported in the
      MLC601 group, although detail was sparse with inconsistent reporting.
      CONCLUSIONS: There is evidence that MLC601 as an add-on to standard treatment
      could be effective in improving functional independence and motor recovery and is
      safe for patients with primarily nonacute stable stroke.

PMID- 23548915
TI  - Chinese medicine NeuroAiD efficacy stroke recovery-extension study (CHIMES-E
      study): an observational multicenter study to investigate the longer-term
      efficacy of NeuroAiD in stroke recovery.
AB  - BACKGROUND: Stroke carries a poor long-term prognosis for death and disability.
      There are few acute treatments that reduce death and disability after stroke. The
      ongoing international, multicenter, randomized, placebo-controlled, double-blind
      CHIMES trial is currently testing the hypothesis that a 3-month course of the
      traditional Chinese medicine MLC601 (NeuroAiD) is superior to placebo in reducing
      neurological deficit and improving functional outcome after acute ischemic stroke
      in patients receiving standard stroke care. This extension study tests the
      hypothesis that at 2 years, an initial 3-month administration of NeuroAiD is
      superior to placebo in reducing neurological deficit and improving functional
      outcome in patients with cerebral infarction of an intermediate range of
      severity. METHODS: Study subjects will be those who are already participants in
      CHIMES - aged above 21 years, had signs and symptoms of acute stroke, 6 <= NIHSS
      <= 14, neuroimaging consistent with ischemic stroke, and received study
      medication within 72 h of stroke onset. A subject will not be eligible for
      inclusion in CHIMES-E if they have withdrawn consent from all participation and
      follow-up for CHIMES. Subjects will be contacted at 6, 12, 18 and 24 months after
      CHIMES enrollment. After verbal consent is obtained, subjects will be assessed
      for functional state by the modified Rankin scale (mRS) and Barthel Index (BI),
      and a history of recurrent vascular events as well as medical events. The primary
      outcome measure will be the mRS at month 24. Secondary outcome measures will be
      mRS and BI at 6, 12 and 18 months, and BI at 24 months. Analysis will be based on
      the intention-to-treat principle. If the number of patients lost to follow-up is
      substantial, a sensitivity analysis based on the last observation carried forward
      method will be carried out, to compare the results with those from the main
      analysis without imputation. Based on a cumulative odds ratio of 1.5 for the
      NeuroAiD group, a two-sided test of 5% type I error and an expected 30% dropout
      rate after 2 years of follow-up for the 1,100 patients recruited into CHIMES, the
      770 subjects with mRS data expected to be available at year 2 yields an 89% power
      to detect a difference in efficacy between NeuroAiD and placebo. CONCLUSIONS:
      This study will provide evidence for the longer-term efficacy of an initial
      course of a neurorestorative therapy after acute ischemic stroke of intermediate
      severity.

PMID- 23548916
TI  - The NeuroAiD II (MLC901) in vascular cognitive impairment study (NEURITES).
AB  - BACKGROUND: A substantial proportion of patients after nondisabling stroke are
      cognitively impaired compared to age- and education-matched community-dwelling
      controls. Moreover, poststroke patients who have 'vascular cognitive impairment
      no dementia' (VCIND) of moderate severity have a high risk of incident dementia,
      dependency and death. Further studies are urgently needed to demonstrate
      effective cognition-enhancing therapies in VCIND given the scarcity of evidence
      based treatment options. NeuroAiD is a traditional Chinese medicine that has been
      shown to induce neuroplasticity, promote cell proliferation and stimulate the
      development of dense axonal and dendritic networks in animal stroke models.
      NeuroAiD may improve cerebral blood flow and functional recovery after stroke in
      patients. OBJECTIVE: To investigate the effects and tolerability of NeuroAiD II
      in patients with VCIND. METHODS: The NeuroAiD II (MLC901) in Vascular Cognitive
      Impairment Study (NEURITES) is a 24-week, double-blind, randomized, placebo
      controlled phase II study of NeuroAiD II in patients with VCIND. The primary
      outcome is executive function as measured by the Verbal Fluency test. Secondary
      outcomes include cognitive assessments such as the ADAS-Cog, MoCA, MMSE and
      Cognitive Battery: activities of daily living as measured by the Alzhei-mer's
      Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale for mild
      cognitive impairment, behavior as measured by the Neuropsychiatric Inventory, and
      depression as measured by the Geriatric Depression Scale and the Beck Depression
      Scale. In addition, there will be novel exploratory outcomes: (a) magnetic
      resonance imaging of lesion location (structural imaging), structural integrity
      of white matter pathways (diffusion tensor imaging), neuronal function (resting
      studies) and perfusion (arterial spin labeling and MR angiography), and (b)
      retinal and optic nerve imaging. Safety and tolerability will be assessed using
      adverse events, laboratory tests and vital signs. CONCLUSIONS: NEURITES has the
      potential to set new standards for the systematic evaluation of Asian traditional
      medicine for integration into standard medicine practice and establishing a novel
      therapeutic approach for improving cognition after stroke.

PMID- 23548917
TI  - NeuroAiD(r) (MLC601) and amyloid precursor protein processing.
AB  - BACKGROUND: Amyloid precursor protein (APP) undergoes cleavage under
      physiological conditions, predominantly by alpha- and gamma-secretases, to form
      the nonpathogenic sAPPalpha and p3 fragments. By contrast, amyloid-beta (Abeta)
      is produced via proteolytic cleavage by beta- and gamma-secretases. In
      Alzheimer's disease (AD), APP is preferentially processed via the amyloidogenic
      pathway, producing large amounts of Abeta that form the major constituent of
      senile plaques and tau-containing neurofibrillary tangles. Similarly, stroke
      patients have a higher level of Abeta around the area of infarct, suggesting that
      Abeta may mediate at least some of the secondary neurotoxicity observed in stroke
      patients. METHODS: To investigate the effects of MLC601 (NeuroAiD((r))) on
      regulation of APP processing, the human neuroblastoma cell line SH-SY5Y was used
      for all experiments. Stocks of MLC601 were prepared at a final concentration of
      50 mg/ml. Cells were treated with different concentrations of MLC601 before
      assessing changes in the levels of released lactate dehydrogenase (LDH), full
      length APP and secreted sAPPalpha. RESULTS: Concentrations of MLC601 between 1
      and 1,000 ug/ml significantly lowered the levels of LDH released into the media
      when compared to control cells. In contrast, MLC601 concentrations at 5,000 and
      10,000 ug/ml resulted in a significant increase in the LDH release. Treatment
      with 100, 500 and 1,000 MUg/ml of MLC601 significantly increases the levels of
      sAPPalpha secreted by SH-SY5Y into the media. Treatment with 1,000 MUg/ml of
      MLC601 significantly decreased the levels of full-length APP. CONCLUSION: MLC601
      is a possible modulator of APP processing and has implications as a putative
      therapeutic strategy for the treatment of poststroke dementia and AD.

PMID- 23548919
TI  - Drugs from natural substances: why study them in cerebral infarction.

PMID- 23548920
TI  - Electrochemical degradation of m-cresol using porous carbon-nanotube-containing
      cathode and Ti/SnO2-Sb2O5-IrO2 anode: kinetics, byproducts and biodegradability.
AB  - The degradation of m-cresol solution was studied using an electrochemical
      oxidation system with Ti/SnO2-Sb2O5-IrO2 anode for anodic oxidation and porous
      carbon-nanotube-containing cathode for H2O2 electrogeneration along with Fe(3+)
      reduction. Organic pollutants were oxidized by hydroxyl radical (OH) formed
      simultaneously in the medium from electro-Fenton reaction in the presence of
      Fe(2+) and at the anode surface from water oxidation. The porous cathode made of
      graphite, carbon nanotube (CNT) and polytetrafluoroethene (PTFE) exhibited a
      higher catalytic activity toward O2 reduction producing H2O2 and Fe(3+) reduction
      for Fe(2+) regeneration, favoring organics degradation by electro-Fenton
      oxidation. The degradation kinetics results revealed that the reaction of m
      cresol cleavage with hydroxyl radicals could be described by pseudo first-order
      kinetics. The progress of organics mineralization demonstrated some byproducts
      were formed during m-cresol degradation. Based on the byproducts identified by GC
      MS and HPLC, the sequential process of m-cresol degradation was proposed.
      Furthermore, the aerobic biological treatment showed that the electrochemical
      treatment was able to evidently enhance the biodegradability of m-cresol
      solution.

PMID- 23548921
TI  - Selective lanthanide sorption and mechanism using novel hybrid Lewis base (N
      methyl-N-phenyl-1,10-phenanthroline-2-carboxamide) ligand modified adsorbent.
AB  - This study aims to develop a highly selective Lewis base adsorbent to investigate
      the selective sorption and recovery of Eu(III) and Sm(III) from wastewater. The
      oxygen and nitrogen donor atoms containing Lewis base N-methyl-N-phenyl-1,10
      phenanthroline-2-carboxamide (MePhPTA) ligand was synthesized and subsequently an
      adsorbent was prepared by direct immobilization onto mesoporous silica.
      Determined maximum adsorption capacities were 125.63 and 124.38 mg/g for Eu(III)
      and Sm(III), respectively. Experiments with mixed-cations solutions showed that
      the sequence of preferential adsorption was Eu(III)>Sm(III). The lanthanide
      sorption by hybrid Lewis base adsorbent (HyLBA) was not adversely affected by the
      presence of sodium, potassium, calcium, magnesium, chloride, sulfate and nitrate
      ions due to strong affinity between hard Lewis acid lanthanide and hard Lewis
      base adsorbent. The crystallography for the Sm-MePhPTA complex suggested that
      MePhPTA was strongly coordinated to Sm(III) with oxygen and nitrogen by forming a
      stable complex with two 5-membered rings. The data clarified that bond lengths
      between Sm(III) and amide oxygen (2.475A) were shorter than SmN (2.662A) in
      phenanthroline moiety indicating strong oxygen driven HyLBA. The results
      suggested that HyLBA has a good prospect of promising applications for
      separation/sorption of lanthanide ions from effluents.

PMID- 23548922
TI  - Mitochondrial and endoplasmic reticulum pathways involved in microcystin-LR
      induced apoptosis of the testes of male frog (Rana nigromaculata) in vivo.
AB  - Previous studies have shown that toxins produced by toxic cyanobacterial blooms
      are hazardous materials. In the present study, 1 MUg/L microcystin-LR (MC-LR) was
      observed to induce apoptosis in the testes of male Rana nigromaculata via the
      mitochondrial and endoplasmic reticulum (ER) pathways at exposure times ranging
      from 7 d to 14 d. The results showed that reactive oxygen species production and
      malondialdehyde content were positively correlated with exposure time.
      Antioxidant enzyme contents, such as reduced glutathione and glutathione
      peroxidase rapidly decreased, implying that the defense system of the testes
      induces oxidative damage. MC-LR significantly stimulated the release of
      cytochrome c in the testes, thereby improving the protein expressions of Bax and
      caspases-3, 8, and 9 (p<0.01) and inhibiting the protein expression of Bcl-2 with
      prolonged exposure (p<0.01). Ultrastructural observations showed distention of
      the mitochondria and endoplasmic reticulum and deformation of the nucleolus.
      Moreover, prolonged exposure times strengthened and weakened the relative
      expression levels of C/EBP homologous protein and GRP78, respectively. These
      results indicate that MC-LR-induced apoptosis of the testes in male frogs in vivo
      may occur through the mitochondrial and ER pathways. It also further proves our
      previous findings that MC-LR can induce toxicity in the male reproductive system
      of R. nigromaculata in vitro. The findings show that MC-LR is highly hazardous to
      frogs and that the accepted drinking water limit of 1 MUg/L MC-LR exerts
      significant toxicity to amphibians.

PMID- 23548923
TI  - Renoprotective effect of pioglitazone by the prevention of glomerular
      hyperfiltration through the possible restoration of altered macula densa
      signaling in rats with type 2 diabetic nephropathy.
AB  - BACKGROUND/AIMS: Pioglitazone (PGZ), one of the thiazolidinediones, has been
      known to show renoprotective effects. In this study, we focused on the effect of
      PGZ on glomerular hyperfiltration (GHF), resultant glomerular injury and altered
      macula densa signaling as a cause of sustained GHF through modified
      tubuloglomerular feedback in rats with diabetic nephropathy. METHODS: Kidneys
      from 24-week-old male OLETF rats and LET rats, nondiabetic controls, were used
      for the experiment. PGZ was administered (10 mg/kg/day, p.o.) for 2 weeks from 22
      to 24 weeks of age in some of the OLETF rats (OLETF+PGZ). RESULTS: Parameters
      relating GHF, kidney weight, creatinine clearance, urine albumin/creatinine ratio
      and glomerular surface were all increased in OLETF rats and partially restored in
      OLETF+PGZ rats. Expressions of desmin and TGF-beta were also increased in OLETF
      rats and restored in OLETF+PGZ rats. The changes in TGF-beta expression were
      confirmed to be independent of podocyte number. Finally, the immunoreactivity of
      neuronal nitric oxide synthase (nNOS) and cyclooxygenase 2 (COX-2) in the macula
      densa was assessed for the evaluation of macula densa signaling. Altered
      intensities of nNOS and COX-2 in OLETF rats were restored in OLETF+PGZ rats,
      which agreed with the gene expression analysis (nNOS: 100.2 +/- 2.9% in LET, 64.2
      +/- 2.7% in OLETF, 87.4 +/- 12.1% in OLETF+PGZ; COX-2: 100.8 +/- 7.4% in LET,
      249.2 +/- 19.4% in OLETF, 179.9 +/- 13.5% in OLETF+PGZ; n = 5) and the
      semiquantitative analysis of nNOS/COX-2-positive cells. CONCLUSION: PGZ
      effectively attenuated the GHF and hyperfiltration-associated glomerular injury
      in diabetic nephropathy. The restoration of altered macula densa signaling might
      be involved in the renoprotective effect of PGZ.

PMID- 23548924
TI  - Neutrophils in the innate immunity conundrum of cystic fibrosis: a CFTR-related
      matter?

PMID- 23548925
TI  - GTPase switch: Ras then Rho and Rac.

PMID- 23548926
TI  - Cancer stem cells: the challenges ahead.
AB  - Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis
      and the seeds of metastases. However, their existence and role remain a topic of
      intense debate. Recently, the identification of CSCs in endogenously developing
      mouse tumours has provided further support for this concept. Here I discuss the
      challenges in identifying CSCs, their dependency on a supportive niche and their
      role in metastasis, and propose that stemness is a flexible - rather than fixed -
      quality of tumour cells that can be lost and gained.

PMID- 23548927
TI  - Formin' cables under stress.
AB  - How application of force affects actin remodelling during mechanotransduction has
      remained unclear. Mechanical manipulation of the cell cortex is now shown to
      trigger actin monomer release from filaments, which in turn activates formin
      dependent actin filament elongation. This force-sensitive actin polymerization
      does not require GTPases or membrane receptors, but it involves actin itself.

PMID- 23548928
TI  - Cullin' PLK1 from kinetochores.
AB  - To ensure proper attachment of all chromosomes to the spindle, PLK1 has to
      associate with kinetochores during prometaphase and must be released from these
      sites before sister chromatid separation can begin. The monoubiquitylation of
      PLK1 by the ubiquitin ligase CUL3-KLHL22 is now identified as a critical step in
      promoting the release of PLK1 from kinetochores, pushing non-proteolytic
      ubiquitylation into the limelight of cell division research.

PMID- 23548929
TI  - Polycomb complex recruitment in pluripotent stem cells.
AB  - The recruitment of the silencing complex Polycomb group (PcG) to its target sites
      in mammalian cells has remained elusive. A prevalent model proposes that the PRC1
      component is recruited through recognition of methylated H3K27 found at target
      sites occupied by the PRC2 component. However, mounting evidence suggests that
      PRC2-independent mechanisms of PRC1 recruitment exist. Three studies describe
      that the histone demethylase Kdm2b binds to unmethylated CpG islands and recruits
      a subset of PRC1 complexes to chromatin in pluripotent stem cells.

PMID- 23548936
TI  - [Total elbow arthroplasty in complicated distal humerus fracture--a case report].
AB  - BACKGROUND: Total elbow arthroplasty is still a rarely performed surgical
      procedure in distal humerus fractures. Reconstruction and osteosynthesis using
      Locking Compression Plates remains the gold standard for treatment of such types
      of fractures. CASE REPORT: We report a case of 51-year-old man with distal
      humerus fracture and early destabilization of primary osteosynthesis,
      successfully treated with total elbow arthroplasty, resulting in excellent
      physical function of the operated elbow. RESULTS: Several studies performed over
      the last decades demonstrated that total elbow arthroplasty in many cases may be
      a beneficial method of treatment. Osteoporosis, comminuted fractures, older age
      and early destabilization of primary osteosynthesis are the most common
      indications for considering elbow arthroplasty.

PMID- 23548937
TI  - Effect of vitrification on promoter CpG island methylation patterns and
      expression levels of DNA methyltransferase 1o, histone acetyltransferase 1, and
      deacetylase 1 in metaphase II mouse oocytes.
AB  - OBJECTIVE: To investigate the effect of vitrification on Dnmt1o, Hat1, and Hdac1
      promoter CpG island methylation patterns and messenger RNA (mRNA) expression
      levels in mouse metaphase II (MII) oocytes. DESIGN: In vitro study. SETTING:
      Academic institution. ANIMAL(S): Kunming white mice. INTERVENTION(S): After
      vitrification, surviving mouse MII oocytes subjected to methylation and
      expression analysis with fresh oocytes used as a control. MAIN OUTCOME
      MEASURE(S): Expression levels of mRNA as measured by real-time reverse
      transcriptase polymerase chain reaction of methylation patterns of the CpG
      islands in the Dnmt1o, Hat1, and Hdac1 promoters analyzed by bisulfite
      mutagenesis and sequencing. RESULT(S): The methylation patterns of the promoter
      CpG islands in Dnmt1o, Hat1, and Hdac1 were not statistically significantly when
      comparing vitrified oocytes and fresh oocytes. The expression levels of Hat1 and
      Hdac1 mRNA were not statistically significantly different in comparing in
      vitrified oocytes and fresh oocytes. The expression of Dnmt1o mRNA was
      statistically significantly lower in vitrified oocytes compared with fresh
      oocytes. CONCLUSION(S): Vitrification did not statistically significantly alter
      the methylation patterns of the promoter CpG islands in Dnmt1o, Hat1, or Hdac1,
      but did statistically significantly decrease the expression of Dnmt1o mRNA in
      mouse MII oocytes.

PMID- 23548938
TI  - Is intracytoplasmic morphologically selected sperm injection effective in
      patients with infertility related to teratozoospermia or repeated implantation
      failure?
AB  - OBJECTIVE: To evaluate the potential benefit of intracytoplasmic morphologically
      selected sperm injection (IMSI) in patients selected for either severe
      teratozoospermia or repeated implantation failure after conventional
      intracytoplasmic sperm injection (ICSI). DESIGN: Prospective nonrandomized
      observational study. SETTING: University hospital assisted reproduction unit.
      PATIENT(S): Four hundred seventy-eight patients were enrolled to evaluate ICSI
      and IMSI results for two indications. The first group (T) was composed of
      patients with severe teratozoospermia (<10% normal spermatozoa in fresh
      ejaculated and selected semen, according to David classification) and no or one
      previous ICSI failure. In the second group (IF), patients with at least two
      previous failed ICSI attempts were enrolled in absence of severe male factor
      (>10% normal spermatozoa in fresh ejaculated semen and >20% in selected sperm).
      INTERVENTION(S): ICSI/IMSI, biologic, and clinical data collection. MAIN OUTCOME
      MEASURE(S): Live-birth rate (LBR). RESULT(S): In group T, LBR was significantly
      higher when IMSI procedure was used compared with ICSI (38% [50/132] vs. 20%
      [25/126]). However, LBR observed in group IF was not significantly different
      between IMSI and ICSI procedures (21% [19/90] vs. 22% [28/130]). CONCLUSION(S):
      IMSI procedure is a valuable option for patients with severe teratozoospermia at
      their first or second attempts, but it does not improve pregnancy rate in
      patients with repeated ICSI failures in the absence of severe male factor.

PMID- 23548939
TI  - Resistin decreases insulin-like growth factor I-induced steroid production and
      insulin-like growth factor I receptor signaling in human granulosa cells.
AB  - OBJECTIVE: To identify resistin in human ovarian follicles and investigate the
      effect and the molecular mechanisms associated with resistin on steroidogenesis
      in human granulosa cells (GCs). DESIGN: The effects of recombinant human resistin
      on the secretion of progesterone (P) and estradiol (E2) by cultured human GCs
      were investigated. SETTING: Academic institutions. PATIENT(S): Twenty infertile
      and healthy women undergoing IVF. INTERVENTION(S): Primary human GC cultures
      stimulated with recombinant human resistin (10 ng/mL). MAIN OUTCOME MEASURE(S):
      Determination of messenger RNA (mRNA) and protein expression of resistin in fresh
      human GCs by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblot
      and immunohistochemistry, respectively; measurement of P and E2 levels in the
      conditioned media by radioimmunoassay; determination of cell proliferation by
      tritiated thymidine incorporation; and analysis of signaling pathways activation
      by immunoblot analysis. RESULT(S): Human GCs and theca cells express resistin. In
      primary human GCs, resistin decreases P and E2 secretion in response to insulin
      like growth factor I (IGF-I). This was associated with a reduction in the P450
      aromatase and P450scc (cholesterol side-chain cleavage cytochromes P450)
      (P450scc) protein levels but not those of 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD) or steroidogenic acute regulatory protein (StAR) and with a decrease
      in IGF-I-induced IGF-I receptor and mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Resistin
      treatment does not affect IGF-I-induced cell proliferation and basal
      steroidogenesis (there is no IGF-I or follicle-stimulating hormone stimulation).
      In the basal state, resistin rapidly stimulates Akt and MAPK ERK1/2 and p38
      phosphorylation in primary human GCs. CONCLUSION(S): Resistin is present in human
      GCs and theca cells. It decreases P and E2 secretion, P450scc and P450 aromatase
      protein levels, and IGF-IR signaling in response to IGF-I in primary human GCs.

PMID- 23548940
TI  - Identification of a novel sperm motility-stimulating protein from caprine serum:
      its characterization and functional significance.
AB  - OBJECTIVE: To identify and characterize a novel sperm motility-stimulating
      protein (MSP) from caprine serum. DESIGN: Prospective experimental study.
      SETTING: Research laboratory. ANIMAL(S): Rabbits and male and female BALB/c mice.
      INTERVENTION(S): Protein purification by conventional methods and functional and
      immunological characterization. MAIN OUTCOME MEASURE(S): MSP was purified, purity
      was checked, and molecular weight was determined. Surface localization, tissue
      distribution, and IVF for contraceptive efficacy were studied. RESULT(S): MSP is
      a heat-stable 66-kDa monomeric novel protein. At 0.9 MUM, it showed much higher
      forward motility and longer motility maintenance than other known activators.
      Studies with the motility analyzers CASA and SPERMA showed an increase in
      horizontal and vertical velocities, respectively. MSP action was cyclic AMP
      independent. Its occurrence was higher in testis, although blood was the richest
      source. MSP was localized throughout the cell surface of spermatozoa. Its
      antibody caused significant inhibition of sperm motility and inhibited
      fertilization up to 100% at 1:25 dilution, which showed its contraceptive
      efficacy. CONCLUSION(S): MSP has high efficacy to stimulate sperm forward
      motility and thus may be used in biomedical application in infertility clinics,
      animal breeding centers, poultries, and animal conservation centers.

PMID- 23548941
TI  - Why we may abandon basal follicle-stimulating hormone testing: a sea change in
      determining ovarian reserve using antimullerian hormone.
AB  - Antimullerian hormone is the most informative serum marker of ovarian reserve
      currently available and should be considered an important part of any
      contemporary reproductive medicine practice. It is both more convenient and
      informative than basal FSH and can be assessed at any point in the cycle. It is
      the most useful serum method of determining ovarian reserve, which guides
      pretreatment counseling, choice of infertility treatment, and avoidance of
      ovarian hyperstimulation. The future role of basal FSH testing is in doubt.

PMID- 23548942
TI  - In vitro fertilization with single euploid blastocyst transfer: a randomized
      controlled trial.
AB  - OBJECTIVE: To determine whether performing comprehensive chromosome screening
      (CCS) and transferring a single euploid blastocyst can result in an ongoing
      pregnancy rate that is equivalent to transferring two untested blastocysts while
      reducing the risk of multiple gestation. DESIGN: Randomized, noninferiority
      trial. SETTING: Academic center for reproductive medicine. PATIENT(S): Infertile
      couples (n = 205) with a female partner less than 43 years old having a serum
      anti-Mullerian hormone level >= 1.2 ng/mL and day 3 FSH <12 IU/L.
      INTERVENTION(S): Randomization occurred when at least two blastocysts were
      suitable for trophectoderm biopsy. The study group (n = 89) had all viable
      blastocysts biopsied for real-time, polymerase chain reaction-based CCS and
      single euploid blastocyst transfer. The control group (n = 86) had their two best
      quality, untested blastocysts transferred. MAIN OUTCOME MEASURE(S): The ongoing
      pregnancy rate to >= 24 weeks (primary outcome) and the multiple gestation rate.
      RESULT(S): The ongoing pregnancy rate per randomized patient after the first ET
      was similar between groups (60.7% after single euploid blastocyst transfer vs.
      65.1% after untested two-blastocyst transfer; relative risk [RR], 0.9; 95%
      confidence interval [CI], 0.7-1.2). A difference of greater than 20% in favor of
      two-blastocyst transfer was excluded. The risk of multiple gestation was reduced
      after single euploid blastocyst transfer (53.4% to 0%), and patients were nearly
      twice as likely to have an ongoing singleton pregnancy (60.7% vs. 33.7%; RR, 1.8;
      95% CI, 1.3-2.5). CONCLUSION(S): In women <= 42 years old, transferring a single
      euploid blastocyst results in ongoing pregnancy rates that are the same as
      transferring two untested blastocysts while dramatically reducing the risk of
      twins.

PMID- 23548943
TI  - Unilateral pallidal deep brain stimulation in a patient with dystonia secondary
      to episodic ataxia type 2.
AB  - BACKGROUND/AIMS: This paper describes the use of deep brain stimulation (DBS) of
      the globus pallidus internus (GPi) in the treatment of secondary dystonia caused
      by expisodic ataxia type 2 (EA2). METHODS: We present the case of a patient with
      EA2, an autosomal dominant condition, who developed late-onset cervical and right
      upper limb segmental dystonia. The patient underwent left GPi DBS. RESULTS:
      Within 4 months of commencing stimulation of the left GPi, the patient had
      resolution of his neck pain and was able to keep the head straighter for longer
      time intervals. There was also improvement in right arm segmental dystonia. There
      was an improvement in the Toronto Western Spasmodic Torticollis Rating Scale
      (TWSTRS 21.5) of 55% at 4 months and of 51% at 22 months. CONCLUSION: The
      treatment of secondary dystonia is difficult and the results with GPi DBS are
      less favourable compared with primary dystonia. This case illustrates the
      successful treatment of secondary dystonia caused by EA2.

PMID- 23548945
TI  - Osthole ameliorates renal ischemia-reperfusion injury by inhibiting inflammatory
      response.
AB  - INTRODUCTION: Renal ischemia-reperfusion (I/R) injury is a primary cause of acute
      renal failure that results in high mortality. This study aimed to investigate the
      effect of osthole, a natural coumarin derivative, on renal I/R injury in a rat
      model. MATERIALS AND METHODS: Rats were randomly allocated to the sham operation
      + vehicle, I/R + vehicle, and I/R + osthole groups. Renal I/R injury was induced
      by clamping the left renal artery for 45 min followed by 12 h of reperfusion and
      a contralateral nephrectomy. Osthole (40 mg/kg) was intraperitoneally injected 30
      min before inducing I/R. Renal function and histological damage were determined
      subsequently. Myeloperoxidase activity, monocyte/macrophage infiltration, as well
      as tumor necrosis factor-alpha, IL-1beta, and activated p38 mitogen-activated
      protein kinase expression in kidneys were also assessed. RESULTS: Osthole
      treatment significantly ameliorated I/R-induced renal functional and
      morphological injuries. Moreover, osthole treatment attenuated myeloperoxidase
      activity, monocyte/macrophage infiltration, and tumor necrosis factor-alpha, IL
      1beta, and activated p38 mitogen-activated protein kinase expression in kidneys.
      CONCLUSIONS: Osthole treatment ameliorates renal I/R injury by inhibiting
      inflammatory responses in kidneys. Thus, osthole may represent a novel practical
      strategy to prevent renal I/R injury.

PMID- 23548944
TI  - Mobility, disability, and social engagement in older adults.
AB  - OBJECTIVE: To examine cross sectional associations between mobility with or
      without disability and social engagement in a community-based sample of older
      adults. METHODS: Social engagement of participants (n = 676) was outside the home
      (participation in organizations and use of senior centers) and in home (talking
      by phone and use of Internet). Logistic or proportional odds models evaluated the
      association between social engagement and position in the disablement process (no
      mobility limitations, mobility limitations/no disability, and mobility
      limitations/disability). RESULTS: Low mobility was associated with lower level of
      social engagement of all forms (Odds ratio (OR) = 0.59, confidence intervals
      (CI): 0.41-0.85 for organizations; OR = 0.67, CI: 0.42-1.06 for senior center; OR
      = 0.47, CI: 0.32-0.70 for phone; OR = 0.38, CI: 0.23-0.65 for Internet). For
      social engagement outside the home, odds of engagement were further reduced for
      individuals with disability. DISCUSSION: Low mobility is associated with low
      social engagement even in the absence of disability; associations with disability
      differed by type of social engagement.

PMID- 23548946
TI  - Reply: To PMID 22964496.

PMID- 23548947
TI  - Thymic epithelial cells use macroautophagy to turn their inside out for CD4 T
      cell tolerance.
AB  - During development in the thymus, each T lymphocyte is equipped with one,
      essentially unique, T cell receptor (TCR)-specificity. Due to its random nature,
      this process inevitably also leads to the emergence of potentially dangerous T
      lymphocytes that may recognize 'self.' Nevertheless, autoimmune tissue
      destruction, the cause of diseases such as multiple sclerosis and diabetes, is
      the exception rather than the rule. This state of immunological self-tolerance is
      to a large degree based upon a process called 'negative selection': prior to
      joining the circulating lymphocyte pool, immature T cells test their receptor on
      self-antigens within the thymic microenvironment, and TCR engagement at this
      immature stage elicits an apoptotic suicide program. We now find evidence that
      macroautophagy supports the tolerogenic presentation of self-antigens in the
      thymus.

PMID- 23548949
TI  - Sublingual immunotherapy for experimental allergic conjunctivitis in a murine
      model induced by Dermatophagoides farinae allergen.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) is a clinically effective treatment
      in allergic conjunctivitis (AC); however, the mechanism of the underlying
      pharmacodynamics remains unclear. Here, we investigate the efficacy and the
      mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine
      in a murine AC model. METHODS: A murine model of AC caused by Der f extract was
      developed in BALB/c mice by repeated application of allergen. Sensitized mice
      were SLIT treated by Der f drops and subsequently analyzed for AC symptoms,
      histopathological and immunological parameters. RESULTS: In this study, Der f
      extract successfully induced the symptoms of AC in BALB/c mice. In these
      sensitized mice, clinical symptoms (scratching behavior, lacrimation,
      conjunctival hyperemia and edema), immunological and histopathological findings
      (inflammatory cell infiltration) were very similar to those in human AC. SLIT
      treatment of sensitized mice markedly reduced the clinical and histopathological
      symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der
      f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a
      significant increase in Der f-specific IgG4 and Th1 cytokine interferon-gamma.
      CONCLUSIONS: SLIT with Der f drops is a potentially effective means of
      immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune
      response.

PMID- 23548950
TI  - [Paget's disease of bone: new therapeutic strategies].
AB  - Paget's disease of bone is a chronic disorder of unknown etiology that can result
      in enlarged and misshapen bones. The excessive breakdown and formation of bone
      tissue cause affected bones to weaken, resulting in pain, misshapen bones,
      fractures, and arthritis in the joints. In most cases the diagnosis is achieved
      casually, as only 5% of patients develop burning pain at the level of affected
      bones. As regards therapy, the use of anti-reabsorbing drugs, such as
      bisphosphonates and calcitonin, appears reasonable. Given the disease
      pathogenesis, the administration of denosumab and tocilizumab may be a valuable
      alternative to inhibit RANK expression, and thus osteoclast formation, and
      interleukin-6 production.

PMID- 23548951
TI  - [The development of a bedside cart for the management of acute respiratory
      failure with non-invasive ventilation in Internal Medicine wards].
AB  - In order to improve the organization of a General Medical ward without a real
      critical care area and to optimize treatment of patients with acute respiratory
      failure, we developed a cart for non-invasive ventilation to be used at the
      patient bedside. In the rear panel, we set two i.v. drip poles used for i.v.
      therapy and to hold two Venturi-like flow generators for continuous positive
      airway pressure. On the top, two ventilators are present, a smaller one
      (domiciliary) and a bigger one (intensive care unit ventilator). In the front
      panel, there are 4 drawers called "blood - drugs", "oxygenation", "CPAP",
      "ventilation", in which all the devices for ventilation, oxygenation, aerosol and
      medical therapy are easily and quickly available. The management of acute
      respiratory failure is simpler, easier and safer with this cart: each necessary
      device is immediately available, and this avoids wasting time. This bedside non
      invasive ventilation cart, as far as the cardiac emergency cart, can be useful in
      general medical wards lacking a critical care area in order to improve
      interventions in patients with acute respiratory failure.

PMID- 23548952
TI  - [Management of children with headache in a Pediatric Emergency Department before
      and after the introduction of the Second International Classification of Headache
      Disorders (ICHD-II)].
AB  - The aim of this study was to evaluate how the management of children admitted
      with headache to a Pediatric Emergency Department, was modified by the
      introduction of the Second International Classification of Headache Disorders (
      ICHD-II) published in 2004. The complexity and average costs of the services
      provided to patients in 2002 and 2011 were compared. The results revealed a
      decrease in the number of tests performed and in-hospital admissions. However,
      tests were more complex, and an increase in requests of specialist advice was
      observed. We hypothesized that this change may be related to the introduction of
      ICHD-II, which suggests a more rational approach to the child with headache and a
      better use of hospital resources.

PMID- 23548953
TI  - [Cardiovascular risk profile of patients with psoriasis].
AB  - The aim of this study was to assess the cardiovascular risk profile of patients
      with psoriasis compared to patients without psoriasis. A case-control assay was
      performed using 143 cases (psoriasis patients) and 104 controls (patients without
      psoriasis). We assessed the presence of hypertension, lipid profile (HDL,
      triglycerides), diabetes, and body mass index in both cases and controls.
      Psoriasis patients showed an unfavorable cardiovascular risk profile and a higher
      risk of cardiovascular events and metabolic syndrome than patients without
      psoriasis.

PMID- 23548954
TI  - [Clinical use of virally inactived plasma. The experience of Blood Transfusion
      Unit in Mantova, Italy].
AB  - BACKGROUND: Fresh Frozen Plasma (FFP) is a blood component whose clinical use is
      widespread worldwide. Transfusion safety of this product is ensured by legally
      obligatory tests. Although these tests are carried out on each plasma donation,
      safety levels can be further improved by using some technical procedures, such
      as, among others, methylene blue (MB) and solvent-detergent (SD) viral
      inactivation methods. The DMTE (Blood Transfusion Unit) in Mantova has used the
      pharmaceutical-like SD virally inactivated plasma since 2007 (Plasmasafe,
      Kedrion) as replacement of the PFC by each single donor. Guidelines for the usage
      of both products are the same. MATERIALS AND METHODS: With the main aim of
      assessing the therapeutic effectiveness and safety of Plasmasafe, we decided to
      clinically monitor transfusions performed with this product on patients of the
      Intensive Care Unit at the city hospital in Mantova. In addition, we controlled
      some coagulation parameters (PT, aPTT, ATIII, Fibrinogen, PC, PS, FV, FVII,
      FVIII) before and 24 hours after the Plasmasafe infusion. RESULTS: From a
      clinical point of view, the use of Plasmasafe always led to a significant
      reduction, or complete stop, of the bleeding. No transfusion-related adverse
      events were recorded. As regards, the most relevant laboratory results, a marked
      increase in the above mentioned hemostatic parameters was detected. Furthermore,
      patients transfused with this product received a mean volume significantly lower
      than an historical cohort of patients treated with FFP (503 mL with Plasmasafe
      versus 1549 mL with FFP, P<0.001). CONCLUSIONS: The results of our study clearly
      document that Plasmasafe, a virally inactivated pharmaceutical-like product with
      a standardized content of coagulation factors, is a safe and cost-effective
      treatment, able to rapidly correct hemostatic abnormalities, for critical
      patients.

PMID- 23548955
TI  - [Severe hyponatremia secondary to the syndrome of inappropriate secretion of
      antidiuretic hormone].
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a
      common and multifactorial cause of hyponatremia that is often overlooked. The
      common pathophysiological mechanism is the increased production and/or action of
      antidiuretic hormone within the kidney, resulting in hypotonic hyponatremia.
      Inadequate correction of hyponatremia may have fatal neurological consequences
      leading to central pontine myelinolysis. We report the case of a patient with a
      history of recent head trauma, who came to our observation for acute-onset mental
      confusion secondary to severe hyponatremia due to SIADH of combined etiology.

PMID- 23548956
TI  - [Allergic rhinitis: pathology of general interest].
AB  - Allergic rhinitis may appear of little value but at present its high and still
      increasing prevalence, its socio-economic burden, the frequent association with
      asthma and the significant impairment of quality of life in affected patients
      make it a disease of general importance. The ARIA (Allergic Rhinitis and its
      Impact on Asthma) guidelines allow to properly recognize the mild forms and the
      moderate/severe forms, and, based on the duration of symptoms, the intermittent
      and persistent forms. Etiologic diagnosis can be suspected by history data but
      the certainty can be achieved only by allergy testing. The treatment is mainly
      based on oral or nasal topical antihistamines and topical corticosteroids, that
      ensure in most cases a satisfactory control of symptoms. However, there are
      patients who have an insufficient response to drugs, event at high doses. Recent
      studies showed that patients not controlled by drug treatment achieve a
      significant benefit from allergen specific immunotherapy, currently available by
      the subcutaneous and sublingual route. This should be considered as a criterion
      to choose patients for specific immunotherapy, who must be referred to the
      allergy specialist.

PMID- 23548957
TI  - [Diagnostic approach to the mild head trauma of the adult in Emergency Medicine:
      between biomarkers and imaging].
AB  - Head trauma is one of the most frequent disabling diseases, with annual incidence
      of approximately 250-600 patients per 100,000, and mortality of 17 cases per
      100,000. The mild head injury is nearly 15 times more frequent than the moderate,
      and more than 20 times than the severe. Although there are still contradictions
      regarding the clinical significance of the term "head injury", it can not be
      considered synonymous with traumatic brain injury. The main challenge in the
      diagnosis lies in the fact that severe intracranial lesions are often associated
      with mild head injury, especially in the presence of specific risk factors.
      Despite the diagnostic gold standard is represented by computed tomography (CT),
      its systematic performance in all patients is unadvisable for limited prevalence
      of positivity, radiological risk, high cost and complexity. Several potential
      biomarkers have been proposed for the screening of patients, but protein S100B
      seems now the most promising for some clinical and analytical considerations.
      After performing a meta-analysis of clinical trials in patients with mild head
      injury, we calculated a cumulative area under the curve of 0.753 (95% CI, 0.752
      0.754), a negative predictive value of 97.7% (95% CI, 97.5-97.8 %) and positive
      predictive value of 23.6% (95% CI, 23.2-24.0%) for brain injury. We therefore
      developed a diagnostic algorithm based on the preliminary assessment of the
      Glasgow Coma Scale (GCS). Patients with GCS <14 are subjected to CT, those with
      values GCS14-15 without risk factors are discharged, whereas protein S100B is
      assessed stat in those with GCS 14-15 and the presence of risk factors. According
      to the value of the marker, patients with a concentration below the diagnostic
      cut-offs are discharged, whereas CT is performed in those with higher
      concentrations. By combining the percentage of positive CT scans in patients with
      mild head trauma and the negative predictive value of protein S100B, this
      protocol would safely abate unnecessary CT by 30-50% and costs by 28%.

PMID- 23548958
TI  - Pathological characteristics, biochemical recurrence and functional outcome in
      radical prostatectomy patients on statin therapy.
AB  - INTRODUCTION: We assessed the pathological characteristics of the radical
      prostatectomy specimen, the rate of biochemical failure and the functional
      outcome after surgery, in terms of incontinence and erectile dysfunction rate, in
      patients on statin medication. MATERIALS AND METHODS: A total of 588 patients
      with a mean age 65.2 years (SD = 5.7 years) participated in the study. All
      patients were contacted and interviewed. RESULTS: Users who had been on statin
      medication for more than 2 years had lower levels of preoperative serum PSA (p =
      0.034), a 2.76 times greater likelihood of being staged as pT3a to pT3b rather
      than pT2a to pT2c, and a 5.39 times greater likelihood of having a postoperative
      Gleason score equal to seven or more. Positive surgical margins and urinary
      incontinence were not significantly associated with statin use. The probability
      of erectile dysfunction was significantly greater for statin users. CONCLUSION:
      Statin medication was associated with a statistically significantly lower PSA
      value and an increased rate of high Gleason score and pathologic stage in
      patients receiving medication for more than 2 years. Statins were found to be an
      independent predictor of recurrence. Lastly, statin users were more likely to
      present with preoperative and postoperative erectile dysfunction.

PMID- 23548959
TI  - Initial experience with single-vessel cannulation for venovenous extracorporeal
      membrane oxygenation in pediatric respiratory failure.
AB  - OBJECTIVES: Venovenous extracorporeal membrane oxygenation has been used to
      provide cardiopulmonary support in critically ill infants and children. Recently,
      dual-lumen venovenous extracorporeal membrane oxygenation has gained popularity
      in the pediatric population. Herein, we report our institutional experience using
      a bicaval dual-lumen catheter for pediatric venovenous extracorporeal membrane
      oxygenation support, which has been our unified approach for venovenous
      extracorporeal membrane oxygenation since 2009. DESIGN: This study is a
      retrospective review. SETTING: The setting is a tertiary children's hospital in a
      major metropolitan area. PATIENTS: Between 2009 and 2011, 11 patients were
      cannulated using a dual-lumen bicaval venous catheter. Patient demographics,
      cannulation details, circuit complications, complications of catheter use, and
      patient outcomes were collected from a retrospective chart review. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Eleven of the patients were cannulated for
      venovenous extracorporeal membrane oxygenation using the dual-lumen bicaval
      cannula. The median age at the time of venovenous cannulation was 1.9 years
      (range, 0.14-17.1), and the median weight was 10.2 kg (range, 3-84). Three
      patients (27%) required conversion to venoarterial extracorporeal membrane
      oxygenation. The median duration of extracorporeal membrane oxygenation support
      was 10 days (2-38 days). Fifty-five percent of patients suffered from a bleeding
      complication (disseminated intravascular coagulation, pulmonary hemorrhage, or
      intraventricular hemorrhage), and 45% had a circuit complication. Adequate flow
      rates were achieved in all patients. The overall hospital mortality in the series
      was 55%. There were no cannula-related complications. CONCLUSIONS: This review
      presents the first single-institution experience with the dual-lumen Avalon
      cannula in pediatric patients. Preliminary results indicate that the catheter can
      be safely placed and has an acceptable complication profile; however, continued
      study within larger trials is necessary to fully ascertain the clinical profile
      of this catheter.

PMID- 23548961
TI  - Assessment of modified ultrafiltration hemodynamic impact by pressure recording
      analytical method during pediatric cardiac surgery.
AB  - OBJECTIVE: Modified ultrafiltration is commonly used in pediatric cardiac
      surgery. Although its clinical benefits are currently debated, modified
      ultrafiltration has proved to improve mean arterial pressure in the first
      postoperative hours. Aim of our study was to measure cardiac index, stroke volume
      index, and mean arterial pressure modification before and after modified
      ultrafiltration by means of Pressure Recording Analytical Method. DESIGN: Single
      center prospective observational cohort study. SETTING: Pediatric cardiac surgery
      operating room. PATIENTS: Children below 20 kg that are included in the
      "pediatric" mode of Pressure Recording Analytical Method. MEASUREMENTS AND MAIN
      RESULTS: Forty patients were enrolled in this study. Median age, weight, and body
      surface area at surgery were 3 months (interquartile range, 10 days to 3.5 yr),
      5.6 (3.1-15) kg, and 0.31 (0.21-0.56), respectively. During the modified
      ultrafiltration procedure, a median volume of 17 mL/kg (11-25) was ultrafiltered
      and a median volume of 11 mL/kg (6-17) was reinfused with a median final modified
      ultrafiltration balance of -0.15 mL/kg (-4.0 to 0.1). By univariate analyses,
      there was a 10% increase in postmodified ultrafiltration mean, systolic and
      diastolic pressures (p = 0.01), stroke volume index (p = 0.02), and cardiac index
      (p = 0.001) without significant changes in heart rate, central (left and right)
      venous pressures, stroke volume variation, and inotropic score. By multivariate
      analysis, when controlling for cardiopulmonary bypass time and age at surgery,
      cardiac index variation was independently associated with lower preoperative body
      surface area (beta coefficient -5.5, p = 0.04). CONCLUSIONS: According to
      Pressure Recording Analytical Method assessment, modified ultrafiltration acutely
      improves myocardial function, as shown by a 10% increase of systemic arterial
      pressure, stroke volume index, and cardiac index. This effect is more pronounced
      in smaller sized patients.

PMID- 23548960
TI  - Critical pertussis illness in children: a multicenter prospective cohort study.
AB  - OBJECTIVE: Pertussis persists in the United States despite high immunization
      rates. This report characterizes the presentation and acute course of critical
      pertussis by quantifying demographic data, laboratory findings, clinical
      complications, and critical care therapies among children requiring admission to
      the PICU. DESIGN: Prospective cohort study. SETTING: Eight PICUs comprising the
      Eunice Kennedy Shriver National Institute for Child Health and Human Development
      Collaborative Pediatric Critical Care Research Network and 17 additional PICUs
      across the United States. PATIENTS: Eligible patients had laboratory confirmation
      of pertussis infection, were younger than 18 years old, and died in the PICU or
      were admitted to the PICU for at least 24 hours between June 2008 and August
      2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 127 patients
      were identified. Median age was 49 days, and 105 (83%) patients were less than 3
      months old. Fifty-five (43%) patients required mechanical ventilation and 12
      patients (9.4%) died during initial hospitalization. Pulmonary hypertension was
      found in 16 patients (12.5%) and was present in 75% of patients who died,
      compared with 6% of survivors (p < 0.001). Median WBC was significantly higher in
      those requiring mechanical ventilation (p < 0.001), those with pulmonary
      hypertension (p < 0.001), and nonsurvivors (p < 0.001). Age, sex, and
      immunization status did not differ between survivors and nonsurvivors. Fourteen
      patients received leukoreduction therapy (exchange transfusion [12],
      leukopheresis [1], or both [1]). Survival benefit was not apparent. CONCLUSIONS:
      Pulmonary hypertension may be associated with mortality in pertussis critical
      illness. Elevated WBC is associated with the need for mechanical ventilation,
      pulmonary hypertension, and mortality risk. Research is indicated to elucidate
      how pulmonary hypertension, immune responsiveness, and elevated WBC contribute to
      morbidity and mortality and whether leukoreduction might be efficacious.

PMID- 23548962
TI  - Fully covered self-expandable metal stents for treatment of benign biliary
      strictures.

PMID- 23548963
TI  - Analysis of the EGFR mutation status in head and neck squamous cell carcinoma
      before treatment with Gefitinib.
AB  - BACKGROUND: The efficacy of chemotherapy in metastatic and recurrent squamous
      cell carcinomas of the head and neck (HNSCC) remains unsatisfactory. Gefitinib
      offers a new therapeutic option with comparable results and better tolerability
      than chemotherapy. We conducted this study to see if mutations in the epidermal
      growth factor receptor (EGFR) might predict the therapeutic benefit in HNSCC
      patients. PATIENTS AND METHODS: In a pilot trial, 8 patients with metastatic or
      recurrent HNSCC were treated palliatively with gefitinib (500 mg/day orally).
      Forceps biopsies were taken to confirm tumor recurrence and to perform an EGFR
      mutation analysis. RESULTS: The EGFR status could be determined in 6 of the 8
      patients. 5 patients had no EGFR gene mutation, and 1 patient showed a silent
      guanine-to-adenosine mutation in position 2607. Even without any relevant
      mutation in the EGFR, we observed partial remission in 3 of 6 patients treated
      with gefitinib. We also observed that an additional 4 patients had stable disease
      for at least 10 weeks. The median progression-free survival was 6.25 months, and
      the median overall survival was 7.39 months. CONCLUSION: In HNSCC, there are
      tumor responses to gefitinib without protein-altering mutations in the EGFR gene.

PMID- 23548964
TI  - Correlation between biological marker expression and F-fluorodeoxyglucose uptake
      in cervical cancer measured by positron emission tomography.
AB  - BACKGROUND: This study aimed to determine whether several biologic markers were
      associated with (18)fluorine-fluorodeoxyglucose ((18)F-FDG) uptake in patients
      with carcinoma of the cervix. PATIENTS AND METHODS: 60 patients with
      International Federation of Gynecology and Obstetrics (FIGO) stages IA2 to IIB
      cervical cancer, who underwent (18)FDG positron emission tomography/computed
      tomography (PET/CT), were included in the current study. All patients underwent
      radical hysterectomy. Tumor sections were stained by immunohistochemistry for
      glucose transporter 1 (GLUT1), carbonic anhydrase-IX (CA-IX), vascular
      endothelial growth factor (VEGF), hexokinase type I (HK-I), hexokinase type II
      (HK-II), and cytoplasmic and nuclear hypoxia-inducible factor (HIF) 1alpha.
      RESULTS: The expression of GLUT1 (p = 0.005), VEGF (p = 0.021), HK-II (p =
      0.009), and cytoplasmic HIF1alpha (p = 0.024) was significantly associated with a
      higher median standardized uptake value (SUVmax). There was a positive
      correlation between (18)F-FDG uptake and GLUT1 (p = 0.008), CA-IX (p = 0.030), HK
      II (p < 0.001) as well as cytoplasmic HIF1alpha (p = 0.016), whereas this
      relationship was not observed among the VEGF, HK-I and nuclear HIF1alpha.
      CONCLUSION: The data presented in this study indicate that (18)F-FDG uptake is
      associated with the presence of GLUT1, VEGF, nuclear HK-II, and cytoplasmic
      HIF1alpha. There was also a significant correlation among the rate of expression
      of GLUT1, HK-II, cytoplasmic HIF1alpha, and CAIX in carcinomas of the cervix.

PMID- 23548965
TI  - Cranial magnetic resonance imaging in the staging of HER2-positive Breast Cancer
      Patients.
AB  - AIM: The aim of the current study was to evaluate whether early detection of
      brain metastases (BMs) could improve survival outcomes in human epidermal growth
      factor receptor 2 (HER2)-positive breast cancer patients. MATERIAL AND METHODS:
      HER2-positive breast cancer patients without BMs who had no neurological symptoms
      within 12 months from diagnosis or relapse time of the disease were included in
      the study. The patients were distributed into 2 groups: Group 1 comprised
      patients without metastases; group 2 comprised patients with metastases. The
      symptomatic historic control group with BMs was defined retrospectively for
      survival comparisons. RESULTS: 55 (57.3%) and 41 (42.7%) patients were in groups
      1 and 2, respectively. 11 of the 96 patients (11.5%) had occult BMs, and 9 of
      them were in group 2 whereas only 2 patients were in group 1 (22% vs. 3.6%,
      respectively; p = 0.008). While the median survival times from the first
      metastasis (28.7 vs. 22.5 months, respectively; p = 0.561) and BM (6.8 vs. 6.1
      months, respectively; p = 0.511) were similar, cerebral death was numerically
      different (16.7% vs. 46.3%; p = 0.221) between asymptomatic (n = 9) and
      symptomatic patients (n = 53). CONCLUSIONS: BMs were detected very rarely in
      asymptomatic, non-metastatic HER2-positive breast cancer patients compared with
      asymptomatic, metastatic patients. Furthermore, although early detection of BMs
      decreases the cerebral death rate, it does not prolong the survival rate in
      metastatic patients.

PMID- 23548966
TI  - Association between the 8473T>C polymorphism of PTGS2 and prostate cancer risk: a
      metaanalysis including 24,716 subjects.
AB  - BACKGROUND: Prostaglandin endoperoxide synthase 2 (PTGS2) is involved in prostate
      cancer (PCa) by stimulating cell proliferation, promoting angiogenesis,
      inhibiting apoptosis, and mediating immune suppression. 8473T>C, located in the
      3' UTR of the PTGS2 gene, has been considered to influence PCa risk. METHODS: We
      searched Medline, PubMed, Elsevier, and Web of Science (updated to February 5,
      2012) using the following search terms: '8473T>C' or 'rs5275', 'genetic variant'
      or 'polymorphism', 'prostate cancer', 'cancer', 'PTGS2' or 'COX-2'. Odds ratios
      with 95% confidence intervals were assessed by using fixed or random effect
      models. Both funnel plot and Egger's test were used to assess the publication
      bias. RESULTS: Finally, 5 case control studies were included. Overall, no
      evidence was observed of a relationship between the 8473T>C and PCa risk in any
      genetic model. No significant association was found in the studies whose controls
      conform to the Hardy-Weinberg equilibrium. In the stratified analysis,
      significant association was detected in other populations (except for
      Caucasians), which were based on hospitals. CONCLUSION: The 8473T>C polymorphism
      may have little association with PCa risk among Caucasians, but might be involved
      in PCa risk in other ethnicities. Nevertheless, more well-designed studies with a
      larger sample size including different ethnicities should be conducted.

PMID- 23548967
TI  - Frequency of computed tomography examinations in the follow-up care of testicular
      cancer patients - an evaluation of patterns of care in Germany.
AB  - BACKGROUND: Exposure to radiation resulting from diagnostic imaging procedures
      probably increases late cancer risk. Patterns of care regarding the application
      of computed tomography (CT) imaging in testicular cancer patients were
      investigated. METHODS: The database of a large German health insurance company
      comprising 850,000 insured men was searched for cases of testicular cancer
      arising in the years 2005 and 2006. The number of CT scans applied during a 3
      year period of follow-up was noted for each individual patient and the resulting
      cumulative radiation dose was estimated. The number of CT scans actually observed
      was compared to guideline recommendations. RESULTS: 177 patients were identified.
      Within the 3-year observation period, patients received a mean of 4.4 CT scans
      (standard error: 0.4) whereas a number of 6.2 would have been expected according
      to contemporary guidelines. Patients were exposed to an estimated total median
      diagnostic radiation dose of 30 millisieverts (mSv) (interquartile range: 10-54
      mSv). CONCLUSION: There is a considerable gap between recommendation and actual
      performance regarding the number of CT scans applied to testicular cancer
      patients. Unfamiliarity of clinicians with guidelines as well as poor acceptance
      of high numbers of CT scans scheduled may have contributed to create this
      particular pattern of care.

PMID- 23548968
TI  - Downregulation of miR-145 expression in oral squamous cell carcinomas and its
      clinical significance.
AB  - BACKGROUND: MicroRNAs have been reported to play roles as oncogenes or tumor
      suppressor genes in human cancers. However, the expression levels of miR-145 in
      oral squamous cell carcinoma (OSCC) are unclear. The purpose of this study was to
      investigate the status of miR-145 expression in OSCC and determine its clinical
      significance. PATIENTS AND METHODS: We examined miR-145 levels in 62 OSCC tissue
      samples and cell lines by quantitative real-time reverse transcription polymerase
      chain reaction (qRT-PCR). The relationship between miR-145 expression and
      clinicopathologic factors of OSCC patients was analyzed. RESULTS: The proportion
      of miR-145 low expression was 82.26% (51/62) among the 62 OSCC patients, and
      expression levels of miR-145 in OSCC tissue samples and cell lines were
      significantly lower than in non-tumor controls. miR-145 expression levels were
      not significantly associated with age (p = 0.607), sex (p = 0.213), location (p =
      0.952), histology (p = 0.603), pT stage (p = 0.305), pTNM stage (p = 0.471), and
      lymphatic metastasis (p = 1.000). CONCLUSION: miR-145 may be involved in the
      early tumorigenesis of oral squamous cells, and might be a potential biomarker in
      the early diagnosis of OSCC.

PMID- 23548969
TI  - Relevance of incidental colorectal FDG-PET/CT-enhanced lesions.
AB  - INTRODUCTION: Positron emission tomography/computed tomographies (PET/CTs) may
      result in incidental findings of fluorodeoxyglucose (FDG)-avid lesions in the
      colon. The aim of this study was to assess the relevance of a colonoscopic workup
      of such lesions. PATIENTS AND METHODS: We retrospectively analysed all PET/CT
      reports (n = 4,973) generated in our nuclear medicine department between May 2006
      and May 2011; in 69 cases a colonoscopic evaluation was recommended for
      incidental FDG-avid lesions. RESULTS: Of these 69 cases, 51 underwent colonoscopy
      because of the potential need for further treatment. The maximum standardized
      uptake values (SUVmax) ranged from 5.0 to 42.0 with an average of 10.9. In 44 of
      the 51 patients, a histopathological abnormality was found on colonoscopy, 44 in
      the location described by PET/CT. A further 38 lesions were identified that were
      not visible on PET/CT. The histopathological evaluation in the 51 patients
      revealed 14 hyperplastic polyps, 27 adenomas with low-grade and 4 with high-grade
      dysplasia, 3 adenocarcinomas and 1 neuro-endocrine tumour. CONCLUSION: Incidental
      findings of focal colorectal FDG uptake should lead to further workup with
      colonoscopy. The SUVmax was not predictive for higher grade histologies. With an
      SUV of 5 the yield was high for colonic premalignant and malignant lesions.
      However, malignancy cannot be ruled out in focal lesions with an SUV of less than
      5, and for individual patients a colonoscopy should not be ruled out.

PMID- 23548970
TI  - Loss of transfusion dependency following deferasirox treatment of iron overload
      in a woman with myelofibrosis and spherocytosis - a case report.
AB  - BACKGROUND: Many patients with primary myelofibrosis (PMF), a myeloproliferative
      neoplasm, become transfusion dependent due to anemia. In these patients,
      transfusion dependency is associated with shortened survival. CASE REPORT: We
      report on a 67-year-old woman who was diagnosed with PMF. Cytogenetic testing
      revealed a karyotype 46,XX, del(20)(q11.2), consistent with a myeloproliferative
      disorder. Although offered to her because of severe anemia and leukocytosis, the
      patient did not consent to allogeneic hematopoietic stem cell transplantation.
      After having received a cumulative number of more than 70 packed red blood cell
      transfusions, iron chelation therapy with deferiprone was initiated to treat iron
      overload and switched to deferasirox after 3 months. Within 2 months of
      deferasirox treatment, serum ferritin concentrations were significantly reduced,
      the patient lost transfusion dependency for 17 months, and normal hemoglobin
      concentrations were recovered. CONCLUSION: Iron chelation treatment with
      deferasirox resulted in an improvement of hematologic parameters and loss of
      transfusion dependency.

PMID- 23548971
TI  - Panitumumab-induced interstitial lung disease in a case of metastatic colorectal
      cancer.
AB  - BACKGROUND: A Japanese postmarketing survey of panitumumab revealed that
      panitumumab-associated interstitial lung disease (ILD) occurred in approximately
      1% (19/1767) of patients, causing death in 36.8% of these cases. CASE REPORT: We
      report the case of a 60-year-old Japanese man who developed ILD associated with
      panitumumab therapy (third-line therapy) for metastatic sigmoid colon cancer
      involving the liver, lymph nodes, and lungs. 2 months after the initiation of
      panitumumab therapy, he developed a progressive nonproductive cough, dyspnea, and
      a fever, and was diagnosed with ILD. Intravenous pulse methylprednisolone
      treatment led to quick recovery. The patient had some risk factors for ILD
      associated with epidermal growth factor receptor (EGFR)-tyrosine kinase
      inhibitors. CONCLUSION: Further studies are required to elucidate the association
      between anti-EGFR antibodies and ILD.

PMID- 23548972
TI  - ECRG1 and its relationship with esophageal cancer: a brief review.
AB  - Esophageal cancer ranks 8th among the most frequently occurring cancers of the
      world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown;
      however, some factors like smoking, alcohol intake, consumption of fungal
      contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages,
      together with various genetic factors, have been found associated with the
      occurrence of this disease in various parts of the world. Much work has been
      carried out to elucidate the role of various gene mutations and polymorphisms in
      esophageal mucosal cancer. Previous studies have suggested that esophageal cancer
      related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family,
      is expressed in normal esophagus, liver, colon and lung tissues, but the
      expression is seen to be down-regulated in tumors, especially in ESCC, and in
      adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been
      studied in particular in a number of cases and has been observed to play an
      active role in the development of ESCC. This suggests that substitution of the
      arginine in the conserved catalytic domain of the ECRG1 protein might reduce its
      catalytic capacity by impacting its 3-dimensional conformation, thereby causing
      the genetic susceptibility to ESCC.

PMID- 23548973
TI  - Comparison of approaches and artefacts in the measurement of detector modulation
      transfer functions.
AB  - In order to investigate the reproducibility of measurements of transmission
      electron microscope detector modulation transfer functions (MTFs) we measure the
      MTF of a charge-coupled device (CCD) camera using five different methods. MTFs
      derived from a sharp edge, a circular aperture and electron holographic
      interference fringes are found to agree closely with one other. The difficulty of
      obtaining accurate measurements of MTFs and the potential of using focused
      electron probes to make direct measurements of MTFs is discussed. We highlight
      the sensitivity of image contrast after deconvolution to small differences in the
      measured MTF.

PMID- 23548974
TI  - Visual evoked potentials in children prenatally exposed to methylmercury.
AB  - Prenatal exposure to methylmercury can cause both neurobehavioral deficits and
      neurophysiological changes. However, evidence of neurotoxic effects within the
      visual nervous system is inconsistent, possibly due to incomplete statistical
      adjustment for beneficial nutritional factors. We evaluated the effect of
      prenatal methylmercury exposure on visual evoked potential (VEP) latencies in
      Faroese children with elevated prenatal methylmercury exposure. A cohort of 182
      singleton term births was assembled in the Faroe Islands during 1994-1995. At age
      7 years, VEP tracings were obtained from 139 cohort subjects after exclusion of
      subjects with abnormal vision conditions. We used multiple regression analysis to
      evaluate the association of mercury concentrations in cord blood and maternal
      hair at parturition with VEP latencies after adjustment for potential confounders
      that included the cord-serum phospholipid concentration of n-3 polyunsaturated
      fatty acids (PUFAs) and the duration of breastfeeding. Unadjusted correlations
      between mercury exposure and VEP latencies were equivocal. Multiple regression
      models showed that increased mercury concentrations, especially in maternal hair,
      were associated with delayed latencies for VEP peak N145. After covariate
      adjustment, a delay of 2.22 ms (p=0.02) was seen for each doubling of the mercury
      concentration in maternal hair. In agreement with neuropsychological findings,
      the present study suggests that prenatal methylmercury exposure may have an
      adverse effect on VEP findings despite the absence of clinical toxicity to the
      visual system. However, this association was apparent only after adjustment for n
      3 PUFA status.

PMID- 23548975
TI  - Risk factors for intraoperative hypotension during thyroid surgery.
AB  - BACKGROUND: Hypotension is a common adverse effect of IV anaesthetics, especially
      during the induction of anaesthesia. The aim of our study was to determine the
      incidence and risk factors for intraoperative hypotension (IOH) in thyroid
      surgery, as well as to determine whether and to what extent IOH affects the
      occurrence of postoperative hypotension. MATERIAL AND METHODS: The study included
      1252 euthyroid patients, ASA 2 and ASA 3 status (American Society of
      Anesthesiologists physical status classification), who had thyroid surgery
      between 2007 and 2011. IOH was defined as a decrease in systolic blood pressure
      of >20% of baseline values. We studied the influence of demographic
      characteristics (sex, age, body mass index-BMI), comorbidity, type and duration
      of surgery, and anaesthesia on the occurrence of IOH. Univariate and multivariate
      logistic regression were used to determine predictors of occurrence of IOH.
      RESULTS: IOH was registered in 6.5% of patients. The most common operation was
      thyroidectomy. Patients with IOH were younger, had lower BMI, and significantly
      less often had hypertension as a coexisting disease. The multivariate regression
      model identified BMI and the absence of hypertension as a coexisting disease, and
      as independent predictors of occurrence of IOH. Significantly more patients with
      IOH had postoperative hypotension (9.9% vs. 2.4%, p=0.000). CONCLUSIONS: IOH is
      common, even during operations of short duration and with minimal bleeding. It is
      necessary to pay special attention to these patients, given that many of these
      patients remained hypotensive during the postoperative period.

PMID- 23548976
TI  - Generalized lymphadenopathy in infancy; a case report.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD) is a rare disease of histiocytic cells, a
      cause of benign cervical lymphadenopathy (LAP) and massive generalized lymph node
      enlargement in children and adults. There are also some reports on involvement of
      other human body organs with or without LAP. CASE PRESENTATION: A 7-month-old
      infant with chief complaint of generalized massive LAP was referred to our
      center. RDD was diagnosed according to clinical manifestations and confirmed
      through histopathologic and immunoreactivity study on the obtained sample by
      cervical lymph node biopsy. CONCLUSION: RDD is not a malignant illness and lymph
      node enlargement most often decreases in its size happens without special
      treatment.

PMID- 23548977
TI  - Active surveillance: current and future directions.

PMID- 23548978
TI  - Active surveillance: patient selection.
AB  - PURPOSE OF REVIEW: This is a summary of the current approach to patient selection
      for active surveillance, including eligibility criteria, current controversies
      and the role of imaging. RECENT FINDINGS: Active surveillance is based on the
      concept that Gleason 6 prostate cancer is, in most cases, an indolent condition
      that poses little or no threat to the patient's life. Substantial recent data
      suggest that Gleason pattern 3 does not have the molecular characteristics of
      malignancy. A subset of patients harbour more aggressive disease that was missed
      on the initial diagnostic biopsies, and a smaller group will progress over time
      to higher grade disease. Active surveillance involves initial expectant
      management for patients with favourable risk disease, and serial biopsy and
      prostate-specific antigen (PSA). Most patients with Gleason 6 prostate cancer are
      candidates. Very low risk patients fulfil the Epstein criteria, with only one or
      two positive cores, no core with more than 50% involvement and a PSA density of
      less than 0.15. Low-risk patients have Gleason 6 disease and PSA 10 or less but
      do not satisfy the Epstein criteria. Higher volume of Gleason 6 disease on biopsy
      predicts for a higher likelihood of higher grade cancer, but in and of itself
      should not mandate treatment. Patients with Gleason 7 in whom the extent of
      Gleason 4 pattern is less than 10% may also be candidates. Patient age,
      comorbidity and personal preferences must also be considered. SUMMARY: Active
      surveillance is an effective and well tolerated method to reduce the
      overtreatment associated with screen-detected prostate cancer. About 50% of newly
      diagnosed patients are eligible for this approach. Multiple factors, including
      patient age, comorbidity, cancer risk category and patient preferences, must be
      considered.

PMID- 23548981
TI  - PharmaTrek: A Semantic Web Explorer for Open Innovation in Multitarget Drug
      Discovery.

PMID- 23548982
TI  - Interactivity, efficiency, and individual differences in mental arithmetic.
AB  - Thinking efficiency was examined in mental arithmetic as a function of the degree
      of interactivity afforded by the task. Participants carried out single-digit
      additions, involving either 7 or 11 numbers, as fast and as accurately as
      possible. They completed the sums in blocks, five from the short 7-number set
      first, and five from the longer 11-number set second. These sets were
      interpolated among a series of other tasks that measured numeracy and arithmetic
      skills, working memory capacity, visuo-spatial processing speed, and attention
      switching, in such a way as to permit the presentation of the sets twice, once
      with each of the sums presented on a piece of paper and participants placing
      their hands flat on the table and once with the sums presented as a set of
      manipulable tokens. Efficiency was measured as the ratio of performance over time
      invested. A significant interaction between condition and set size was observed:
      Efficiency was slightly better in the static condition for short sums but
      declined substantially relative to the interactive condition for long sums.
      Twenty-two percent of the variance in efficiency for hard sums in the static
      condition was explained by arithmetic skills and working memory capacity, whereas
      45% of this variance was explained by arithmetic skills, working memory capacity,
      and attention switching skills in the interactive condition. A separate sample of
      17 participants who provided concurrent verbal protocols as they solved the
      problems revealed that paths to solution and arithmetic strategies were
      substantially transformed by the opportunity to manipulate tokens.

PMID- 23548983
TI  - The musical Stroop effect. Opening a new avenue to research on automatisms.
AB  - The usual color-word Stroop task, as well as most other Stroop-like paradigms,
      has provided invaluable information on the automaticity of word reading. However,
      investigating automaticity through reading alone has inherent limitations. This
      study explored whether a Stroop-like effect could be obtained by replacing word
      reading with note naming in musicians. Note naming shares with word reading the
      crucial advantage of being intensively practiced over years by musicians, hence
      allowing to investigate levels of automatism that are out of reach of laboratory
      settings. But the situation provides much greater flexibility in manipulating
      practice. For instance, even though training in musical notation is often
      conducted in parallel with the acquisition of literacy skills during childhood,
      many exceptions make that it can be easily decoupled from age. Supporting the
      possibility of exploiting note naming as a new tool for investigating
      automatisms, musicians asked to process note names written inside note pictures
      in incongruent positions on a staff were significantly slowed down in both a
      go/no-go task (Experiment 1) and a verbal task (Experiment 2) with regard to a
      condition in which note names were printed inside note pictures in congruent
      positions.

PMID- 23548984
TI  - Auditory distraction compromises random generation. Falling back into old habits?
AB  - Auditory distraction of random generation--a quintessentially executive control
      task--was explored in three experiments. Random number generation was impaired by
      the mere presence of irrelevant auditory sequences that comprise digits, but not
      letters, and then only if the digits were heard in a canonical order (1, 2, 3 ...
      or 3, 2, 1 ...), not in random order (Experiments 1 and 2). Random letter
      generation was impaired by irrelevant letters heard in alphabetical order (a, b,
      c ...) and reversed alphabetical order (i, h, g ...), but not by numbers in
      canonical order or letters in random order (Experiment 3). Attempting to ignore
      canonical sequences--with items that are members of the same category as the to
      be-generated items--reduced the randomness of the generated sequence, by
      decreasing the tendency to change the direction of the produced sequence for
      random number generation, and by increasing resampling of responses for random
      letter generation. Like other selective attention tasks, the cost of distraction
      to random generation appears to stem from preventing habitual responses assuming
      the control of action.

PMID- 23548985
TI  - When body and mind are talking. Interoception moderates embodied cognition.
AB  - Recent research on so-called embodied cognitions strengthens the current view
      that the body and the mind cannot be separated in producing cognitions. But how
      and when does the body talk to the mind? Drawing on the notion that bodily
      processes are transformed into mental action through experiences, it is argued
      that embodied cognitions should be moderated by interindividual differences in
      the sensitivity to stimuli originating inside of the body, that is, by
      interoception. In line with these assumptions, two experiments demonstrate that
      the embodiment of weight and softness in value judgments and person impressions
      is moderated by interoception as assessed by a body-awareness questionnaire
      (Experiment 1) and a heartbeat perception task (Experiment 2). Taken together,
      these findings strongly speak to the notion that bodily processes and the
      experience thereof play an important role in embodiment, thereby extending
      previous research above and beyond the mere demonstration of body-mind
      interactions.

PMID- 23548986
TI  - Memory for words representing modal concepts. Resource sharing with same-modality
      perceptsis spontaneously required.
AB  - The recent grounded cognition literature suggests that modal perception and
      conceptual representations share common modal systems and modal resources. We
      sought to show that memory and memory of words predominantly related to a visual
      modality (e.g., Light) or to an auditory modality (e.g., Song) are hindered more
      by sensory interference from a related than an unrelated modality. This result
      cannot be explained by semantic interference, because the present study
      manipulated interference using meaningless stimuli. Rather, we suggest that
      people spontaneously access conceptual sensory attributes when detecting words
      and when trying to memorize words, and that this process comes with modality
      specific costs. We discuss this finding in the broader context of grounded
      cognition and compare it to previous findings using closely related sensory
      conceptual designs.

PMID- 23548987
TI  - Alexithymia is associated with delayed treatment seeking in acute myocardial
      infarction.

PMID- 23548988
TI  - Hormesis-based anti-aging products: a case study of a novel cosmetic.
AB  - Application of hormesis in aging research and interventions is becoming
      increasingly attractive and successful. The reason for this is the realization
      that mild stress-induced activation of one or more stress response (SR) pathways,
      and its consequent stimulation of repair mechanisms, is effective in reducing the
      age-related accumulation of molecular damage. For example, repeated heat stress
      induced synthesis of heat shock proteins has been shown to have a variety of anti
      aging effects on growth and other cellular and biochemical characteristics of
      normal human skin fibroblasts, keratinocytes and endothelial cells undergoing
      aging in vitro. Therefore, searching for potential hormetins - conditions and
      compounds eliciting SR-mediated hormesis - is drawing attention of not only the
      researchers but also the industry involved in developing healthcare products,
      including nutriceuticals, functional foods and cosmeceuticals. Here we present
      the example of a skin care cosmetic as one of the first successful product
      developments incorporating the ideas of hormesis. This was based on the studies
      to analyse the molecular effects of active ingredients extracted from the roots
      of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of
      mRNAs and proteins in human skin cells. The results showed that the ginsenosides
      extracted from Sanchi induced the transcription of stress genes and increased the
      synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70,
      in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract
      also has significant positive effects against facial wrinkles and other symptoms
      of facial skin aging as tested clinically, which may be due to its hormetic mode
      of action by stress-induced synthesis of chaperones involved in protein repair
      and removal of abnormal proteins. Acceptance of such a hormesis-based product by
      the wider public could be instrumental in the social recognition of the concept
      of hormesis as the beneficial effects of mild stress of choice, and will
      encourage the development of novel health care products with physical,
      nutritional and mental hormetins.

PMID- 23548989
TI  - Stereotactic radiosurgery for trigeminal schwannoma: a clinical retrospective
      study in 52 cases.
AB  - OBJECTIVE: To evaluate the radiological and clinical outcomes in a series of
      patients in whom stereotactic radiosurgery (SRS) was used to treat trigeminal
      schwannomas. METHODS: The records of 52 patients who underwent SRS for trigeminal
      schwannoma were reviewed using a retrospective study. The median patient age was
      47.1 years (range, 18-77); 20 patients (38.5%) had undergone prior tumor
      resection and 32 (61.5%) underwent radiosurgery on the basis of imaging diagnosis
      only. The most frequent presenting symptoms were facial numbness (29 patients),
      jaw weakness (11 patients), facial pain (10 patients) and diplopia (4 patients).
      Fifty-two cases with solid tumors were mainly solid in 44 cases (84.6%), mostly
      cystic in 2 cases (3.8%), and cystic and solid mixed in 6 cases (11.5%). Two
      cases of mostly cystic tumor first underwent stereotactic cystic fluid aspiration
      and intracavitary irradiation, and then had MRI localization scan again for gamma
      knife treatment. The mean tumor volume was 7.2 ml (range, 0.5-38.2). The mean
      prescription radiation dose was 13.9 Gy (range, 11-17), and the mean prescription
      isodose configuration was 47.9%. RESULTS: At a mean follow-up of 61 months
      (range, 12-156), neurological symptoms or signs improved in 35 patients (67.3%),
      14 patients (26.9%) had a stable lesion, and worsening of the disease occurred in
      2 patients (3.8%). On imaging, the schwannomas almost disappeared in 8 (15.4%),
      shrank in 32 (61.5%), remained stable in 5 (9.6%), and increased in size in 7
      patients (13.5%). Tumor growth control was achieved in 45 (86.5%) of the 52
      patients. CONCLUSIONS: SRS is an effective and minimally invasive management
      option for patients with residual or newly diagnosed trigeminal schwannomas. The
      use of SRS to treat trigeminal schwannomas resulted in good tumor control and
      functional improvement.

PMID- 23548990
TI  - Effects of comprehensive health assessment and targeted intervention on chair
      rise capacity in active and inactive community-dwelling older people.
AB  - BACKGROUND: Being able to rise from a chair is an important daily life activity
      that requires sufficient lower extremity muscle power and postural control.
      OBJECTIVE: To assess the effects of an individually tailored intervention on the
      chair rise capacity of active and inactive community-dwelling older men and
      women. METHODS: This study included a community-based sample of >=75-year-olds
      who were randomized into intervention (n = 299) and control (n = 260) groups. The
      intervention started in 2004 and ended in December 2006; all the participants of
      the intervention group received individually targeted physical activity
      counseling annually and had an opportunity to participate in supervised strength
      and balance training once a week. Chair rise tests were conducted annually. The
      mixed model of linear regression was used for unadjusted measurements and age,
      and the Mini-Mental State Examination and functional comorbidity index adjusted
      comparisons of effects of the intervention. RESULTS: The intervention improved
      the chair rise capacity in physically active women (adjusted mean difference 
      1.67 s, 95% confidence interval -3.21 to -0.13, p = 0.02). There was no
      improvement in inactive women or in men, regardless of their physical activity
      level. CONCLUSION: Intervention showed a positive effect on the chair rise
      capacity of physically active community-dwelling older women.

PMID- 23548991
TI  - A case of lymphomatoid papulosis limited to Becker's melanosis.
AB  - Regional lymphomatoid papulosis (LyP) accounts for 2-27% of all LyP cases.
      Several localized dermatoses have been reported in association with Becker's
      melanosis (BM), e.g. acneiform lesions or lichen planus. Here, we report on
      regional LyP confined to the area of BM. A 56-year-old man presented with a 1
      year history of a steadily increasing number of multiple pruritic red papules
      developing on the area of BM, which had occurred on his left shoulder during
      puberty. Histopathological analysis was consistent with regional LyP. Potent
      topical steroids followed by oral doxycycline did not achieve improvement, while
      long-term oral bexarotene treatment ameliorated the skin condition. Recently, the
      proposed entity of 'persistent agmination of LyP' (PALP) has extended the
      clinicopathological observations of regional LyP. Since PALP remains
      controversial, a unifying concept of localized LyP and PALP will be discussed. 

PMID- 23548992
TI  - Metastatic bone disease in the era of bone-targeted therapy: clinical impact.
AB  - Advances in the diagnosis and treatment of tumors by surgery, chemotherapy,
      biotherapy, radiotherapy and other modalities have increased the survival of
      cancer patients over the last 20 years. As a consequence, bone now represents the
      third most common site of metastatic involvement after the lung and liver.
      Approximately 20-25% of patients with neoplastic disease develop clinically
      evident bone metastases (BMs) during the natural course of their illness, with a
      further 50% of such lesions being identified during autopsy. BMs are the major
      cause of morbidity in cancer patients because of their epidemiological and
      clinical impact. Pain is the most frequent symptom in about 75% of patients but
      other serious complications can also occur, such as pathological fractures,
      spinal cord compression, hypercalcemia and bone marrow suppression. These
      complications worsen the patient's general condition and reduce patients'
      mobility, facilitating the development of lung infections, skin ulcers, deep vein
      thrombosis, etc., and ultimately reducing prognosis and quality of life. The
      frequency of serious complications depends on the site and type of lesions and
      the treatment administered. Over the last 10 years, the introduction of
      bisphosphonates for the treatment of patients with BMs has led to a marked
      decrease in the frequency of complications, thus improving quality of life and
      clinical outcome. Furthermore, progress in understanding the pathophysiology of
      bone metastases has resulted in the development of new bone-targeted molecules
      such as denosumab. We therefore felt it would be useful to report on the
      epidemiological, clinical and economic impact of bone disease in a cancer
      setting.

PMID- 23548993
TI  - Linking nonalcoholic fatty liver disease to hepatocellular carcinoma: from
      bedside to bench and back.
AB  - AIMS AND BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and hepatocellular
      carcinoma (HCC) are two major causes of liver disease worldwide. Epidemiological
      and clinical data have clearly demonstrated that NAFLD and its associated
      metabolic abnormalities are a risk factor for HCC. Traditionally, the mechanisms
      whereby NAFLD acts as a risk for HCC are believed to include replicative
      senescence of steatotic hepatocytes and compensatory hyperplasia of progenitor
      cells as a reaction to chronic hepatic injury. Recent years have witnessed
      significant advances in our understanding of the mechanisms underlying the link
      between NAFLD and HCC. METHODS: In the present review, we provide an update on
      the pathophysiological pathways linking NAFLD and its associated metabolic
      derangements to malignant hepatic transformation, with a special focus on insulin
      resistance, adipokines, inflammation, and angiogenesis. We will also discuss the
      potential therapeutic implications that such molecular links carry. RESULTS:
      Although treating NAFLD could reduce the risk of malignant hepatic
      transformation, no long-term studies focusing on this issue have been conducted
      thus far. Insulin resistance, inflammation as well as derangements in adipokines
      and angiogenic factors associated with NAFLD are closely intertwined with the
      risk of developing HCC. CONCLUSIONS: Traditional therapeutic approaches in NAFLD
      including metformin and statins may theoretically reduce the risk of HCC by
      acting on common pathophysiological pathways shared by NAFLD and HCC.

PMID- 23548994
TI  - GHPSS multicenter Italian survey: smoking prevalence, knowledge and attitudes,
      and tobacco cessation training among third-year medical students.
AB  - AIMS AND BACKGROUND: Healthcare professionals have an important role to play both
      as advisers - influencing smoking cessation - and as role models. The aims of
      this study were to examine smoking prevalence, knowledge and attitudes among
      Italian university students attending medical schools using the Global Health
      Professions Student Survey (GHPSS) approach. METHODS AND STUDY DESIGN: A
      multicenter cross-sectional study was conducted among University students of 9
      Italian medical schools (age ranging between 19 and 29 years). The GHPSS
      questionnaire was self-administered. A logistic regression model was used to
      identify possible factors associated with tobacco smoking status. Data were
      analyzed with the software SPSS 19.0 for Windows. RESULTS: Seven hundred thirty
      medical students (response rate 100%) were enrolled. The prevalence of current
      smokers was 20.4% (males 22.4%, females 19.1%). Of the total sample, 87.7%
      believed that health professionals should receive specific training in techniques
      to quit smoking, and 65% believed that health professionals had a role in giving
      advice or information about smoking cessation. However, 89.4% answered that they
      had not received specific training on smoking cessation techniques. Multivariate
      analysis showed that students belonging to universities in southern Italy were
      more likely to be smokers (OR = 2.00; 95% CI: 1.03-3.97). CONCLUSIONS: This
      Italian multicenter survey found that one fifth of future medical doctors are
      smokers. There is a need to adopt a standard undergraduate curriculum containing
      comprehensive tobacco prevention and cessation training to improve their
      effectiveness as role models.

PMID- 23548995
TI  - The "Don't smoke in our home" randomized controlled trial to protect children
      from second-hand smoke exposure at home.
AB  - AIMS AND BACKGROUND: Increasing smoke-free homes is an important public health
      goal, but only few interventions have yielded positive results. The aim of the
      "Don't smoke in our home" trial was to evaluate a counseling intervention focused
      on promoting totally smoke-free homes and cars (TSFHC) delivered to women with
      children resident in four Tuscan towns. METHODS AND STUDY DESIGN: We used a two
      group randomized controlled trial design. Participants were asked about their
      smoking habits and about restrictions on smoking in their homes and cars. All
      women received a self-help booklet promoting TSFHC, and 110 women randomized to
      the intervention also attended brief counseling on second-hand smoke exposure
      protection and received three gifts to remember the commitment to TSFHC. Follow
      up was conducted by phone after four months. RESULTS: We recruited 218 women, 64
      of whom had a university degree and 131 of whom were smokers; 62% reported
      smoking indoors and 58% in cars. Before the intervention, nonsmokers were more
      likely to report totally smoke-free homes (TSFH, 52%) and cars (TSFC, 53%) than
      smokers (26% and 17% respectively; P <0.001). Participants of the experimental
      arm had similar odds as controls of having implemented TSFH after the
      intervention, and nonsignificantly increased odds of having introduced TSFC (odds
      ratio [OR] 1.47; 95% confidence interval [CI] 0.69-3.11), particularly among
      smokers (OR 2.24, 95%CI 0.69-7.26). All participants independently of the study
      arm recorded significant increases of 12 and 15 percentage points in TSFH and
      TSFC, respectively. Few smokers quit smoking (7%), stopped smoking indoors (5%),
      and stopped smoking in cars (7%), with no differences between the intervention
      and control groups. CONCLUSIONS: Adding brief counseling to written materials did
      not significantly increase TSFHC. However, delivering written materials only may
      produce modest but noteworthy TSFHC increases at the population level, even
      though the participants in the study did not represent a population-based sample,
      given the high proportion of highly educated women. Further studies are required
      to confirm these results.

PMID- 23548996
TI  - Variation among local health units in follow-up care of breast cancer patients in
      Emilia-Romagna, Italy.
AB  - AIMS AND BACKGROUND: This study examines the patterns of follow-up care for
      breast cancer survivors in one region in Italy. METHODS AND STUDY DESIGN: This
      retrospective analysis included 10,024 surgically treated women, with incident
      cases of breast cancer in the years 2002-2005 who were alive 18 months after
      their incidence date. Rates of use of follow-up mammograms, abdominal echogram,
      bone scans and chest x-rays were estimated from administrative data and compared
      by Local Health Unit (LHU) of residence. Logistic regression analyses were
      performed to assess possible "overuse", accounting for patient age, cancer stage,
      type of surgery and LHU of residence. RESULTS: A total of 7168 (72.1%) women
      received a mammogram within 18 months of their incidence date, while 6432 (64.2%)
      had an abdominal echogram, 3852 (38.4%) had a bone scan and 5231 (52.2%) had a
      chest x-ray. The rates of use of abdominal echograms, bone scans and chest x-rays
      were substantially higher in the population of breast cancer survivors than in
      the general female population. Taking account of patient age, cancer stage at
      diagnosis and type of surgery, multivariate analyses demonstrated significant
      variation in the use of these tests by LHU of residence. CONCLUSIONS: The
      observed variation in the use of abdominal echograms, bone scans and chest x-rays
      supports the conclusion that there is substantial misuse of these tests in the
      population of postsurgical breast cancer patients in the Emilia-Romagna region in
      Italy. In the absence of a documented survival benefit, overtesting has both a
      human and financial cost. We recommend additional review of the methods of follow
      up care in breast cancer patients in the LHUs of Emilia-Romagna, with the aim of
      developing, disseminating and evaluating the implementation of specific
      guidelines targeting primary care physicians and oncologists providing care to
      breast cancer survivors. Patient education materials may also help to reduce
      unnecessary testing.

PMID- 23548997
TI  - Impact of use of oral anticancer drugs on activity of Italian oncology practices:
      results of a survey conducted by the Italian Society of Medical Oncology (AIOM).
AB  - AIMS AND BACKGROUND: In recent years, the number of oral anticancer drugs used in
      clinical practice has rapidly increased. The Italian Society of Medical Oncology
      (AIOM) conducted a survey to describe the impact of the use of oral anticancer
      drugs on the daily activity of Italian oncology practices. METHODS AND STUDY
      DESIGN: A survey questionnaire was distributed to the coordinators of the
      regional sections of AIOM. A 6-month period was considered, from January 1, 2010
      to June 30, 2010. The survey addressed (1) quantitative aspects of the use of
      oral anticancer drugs; (2) practical aspects in the management of patients
      treated with these drugs; (3) issues related to treatment costs and reimbursement
      procedures. RESULTS: Thirty-six questionnaires were received from institutions
      distributed throughout the Italian territory. Oral anticancer drugs (both
      chemotherapy and molecularly targeted agents) accounted for a significant
      proportion (17%) of prescribed treatments. Among the responding institutions,
      there were different dispensation procedures of oral drugs to patients: drugs
      were dispensed by the pharmacist (57%) or directly by the medical oncologist
      (23%) or nurse (20%). The medical oncologist played a major role in the
      communication with patients (73% alone and a further 24% in cooperation with
      other professional figures) and was the point of reference in the event of side
      effects in 97% of cases. In most cases, the reimbursement of drug costs was
      separated ("File F" procedure) from the flat fare received by the hospital for
      outpatient visits or day-hospital access. CONCLUSIONS: Optimal organization of
      oral anticancer treatment warrants the cooperation and integration of multiple
      professional figures. At least three figures are involved in patient management
      in the hospital: the medical oncologist, the nurse, and the hospital pharmacist.
      Oral anticancer treatments are associated with specific reimbursement issues: in
      the majority of cases, the cost of the drug is reimbursed separately from the
      cost of patient access.

PMID- 23548998
TI  - Uncommon breast malignancies: presentation pattern, prognostic issue and
      treatment outcome in an Italian single institution experience.
AB  - AIMS AND BACKGROUND: Often neglected by large clinical trials, patients with
      uncommon breast malignancies have been rarely analyzed in large series. PATIENTS
      AND METHODS: Of 2,052 patients diagnosed with breast cancer and followed in our
      Institution from January 1985 to December 2009, we retrospectively collected data
      on those with uncommon histotypes, with the aim of investigating their
      presentation characteristics and treatment outcome. RESULTS: Rare histotypes were
      identified in 146 patients (7.1% of our total breast cancer population), being
      classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36
      (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients
      (6.8%). Whereas age at diagnosis was not significantly different among the
      diverse diagnostic groups, patients with medullary and papillary subtypes had a
      higher rate of lymph node involvement, similar to that of invasive ductal
      carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma.
      Overall, in comparison with our invasive ductal carcinoma patients, those with
      rare histotypes showed a significantly lower risk of recurrence, with a hazard
      ratio of 0.28 (95% CI, 0.12-0.62; P = 0.002). CONCLUSIONS: According to our
      analysis, patients with uncommon breast malignancies are often diagnosed at an
      early stage, resulting in a good prognosis with standard treatment.

PMID- 23548999
TI  - Chemotherapy-induced anemia and oncologist perception on treatment: results of a
      web-based survey.
AB  - AIMS AND BACKGROUND: Anemia prevalence and incidence in chemotherapy-treated
      patients is high. Erythropoiesis-stimulating agents (ESAs) are frequently
      employed in the management of chemotherapy-induced anemia. However, other
      treatments such as red blood transfusion or iron supplementation are normally
      used. Recent international guidelines raised some concern about ESAs employment
      with a possible impact in chemotherapy-induced anemia management and changes in
      clinical practice behavior. METHODS: To evaluate opinions about chemotherapy
      induced anemia clinical management preference, the Associazione Italiana
      Oncologia Medica (AIOM) Lombardy section coordinators sent via email a 12-item
      questionnaire about their knowledge on CIA and usual therapeutic strategies to
      manage this adverse event to AIOM Lombardy onco-hematologist members. RESULTS:
      From January 2011 to March 2011, 81 questionnaires were collected with an
      approximated share of 30%. The survey was completed mainly by oncologists (91%)
      aged 35-50 years (50%). Chemotherapy-induced anemia was considered to have
      clinical impact in changing cancer therapeutic strategy by nearly 60% of the
      respondents. ESAs were administered largely (80%) with concomitant iron
      supplementation in 52%; 38% jointly used blood transfusion as part of the
      therapy. Nearly 20% of those who replied correctly employed transferrin
      saturation levels as a marker to guide iron supplementation. Physician
      prescribers strictly followed the guidelines to start and stop ESAs even if 14%
      were negatively influenced by new ASCO recommendations. ESA biosimilars were
      considered future substitutes of originators in 45% of the cases. CONCLUSIONS:
      Chemotherapy-induced anemia was perceived as an adverse event with a mild impact
      on clinical practice. ESAs were largely employed, however the number of
      transfusions and lack of employment of markers of iron depletion suggested that
      adherence to guidelines could be theoretically met but with some discordances
      regarding the most appropriate strategies in daily clinical practice.

PMID- 23549000
TI  - Malignant sacrococcygeal germ cell tumors in children: a 30-year experience from
      a single institution.
AB  - BACKGROUND: Our aim was to analyze treatment results and survival characteristics
      of our patients with malignant sacrococcygeal germ cell tumors. PROCEDURE:
      Patient files of children with malignant sacrococcygeal germ cell tumors, treated
      at our institution between 1979 and 2009, were searched. Patient characteristics,
      histopathological subtypes, extension of disease, alpha-fetoprotein (AFP) level
      at the time of diagnosis and relapse, extent of surgical resection, chemotherapy
      protocols, details of radiotherapy and survival characteristics were recorded.
      RESULTS: A total of 58 patients (M/F = 20/38) with malignant sacrococcygeal germ
      cell tumor was included in analysis. With a mean follow-up of 156 months (range,
      26 days to 288.8 months) overall and event-free survival rates of the 58 patients
      were 50.9% and 43.8%, respectively. AFP status of the patients (37% in patients
      with <10,000 ng/ml, 68.9% in patients with >= 10,000 ng/ml), type of resection
      (total vs others), coccygeal resection, chemotherapy protocol (PEB vs others) and
      number of chemotherapy courses had an impact on event-free survival in univariate
      analysis. In multivariate analysis, AFP status had the greatest effect on
      prognosis. CONCLUSIONS: Our treatment results are worse than those reported in
      the literature. Elevated AFP level at the time of diagnosis had a beneficial
      effect on prognosis, but year of diagnosis, tumor stage, presence of metastasis,
      tumor size and histopathological subtype had no impact on survival in patients
      with malignant sacrococcygeal germ cell tumors.

PMID- 23549001
TI  - First-line irinotecan combined with 5-fluorouracil and leucovorin for high-grade
      metastatic gastrointestinal neuroendocrine carcinoma.
AB  - AIM AND BACKGROUND: High-grade gastrointestinal neuroendocrine neoplasms, ie,
      poorly differentiated neuroendocrine carcinomas, with no effective therapeutic
      approaches, have a high ability to metastasize. METHODS: A review of the hospital
      information system was performed. Patients with histologically proven
      gastrointestinal neuroendocrine carcinoma who were treated with irinotecan
      combined with 5-fluorouracil and leucovorin in a first-line setting were eligible
      for analysis. We extracted information on age, sex, disease stage, laboratory
      findings, radiological findings, pathological findings, chemotherapy,
      effectiveness and adverse events of therapy, and outcomes. RESULTS: Eleven
      patients were included in the study. Partial response was observed in 7 patients.
      Median progression-free survival and overall survival were 6.5 (95% CI, 5.1-7.9)
      and 13.0 (95% CI, 9.8-16.2) months, respectively. No treatment-related deaths
      occurred. CONCLUSIONS: The results demonstrated that irinotecan combined with 5
      fluorouracil and leucovorin is an active regimen with acceptable toxicity for
      patients with metastatic high-grade gastointestinal neuroendocrine carcinoma that
      merits further investigation in prospective trials.

PMID- 23549003
TI  - Curative radiotherapy using different radiation techniques for isolated lung
      metastasis from colorectal cancer.
AB  - AIMS AND BACKGROUND: Surgical resection remains the mainstay for the treatment of
      colorectal lung metastasis, but a group of patients who are medically inoperable
      or unsuitable for surgery are treated with radiotherapy. The purpose of this
      multi-institutional study was to evaluate the clinical outcome and investigate
      the prognostic factors affecting local control and survival in this subset of
      patients. METHODS: We retrospectively analyzed 30 patients with 43 lesions who
      underwent curative radiotherapy for isolated lung metastasis from colorectal
      cancer at nine institutions from 2003 and 2008. A total dose of 42-75 Gy at the
      peripheral planning target volume was administered in 3-35 fractions. The median
      biologically equivalent dose was 84 Gy (range, 58.5-180). RESULTS: Treatment
      response was complete in 10 (33.3%), partial in 13 (43.3%), stable in six
      (20.0%), and progressive in one patient (3.3%). The median follow-up period for
      all patients was 29.0 months (range, 5.0-93.8). Kaplan-Meier local control at 5
      years was 44%. The median survival was 46.2 months, and the 5-year overall
      survival was 47%. Twenty-three patients (77%) experienced treatment failure, most
      of which were intrapulmonary failure. The intrapulmonary relapse-free survival
      and overall relapse-free survival at 5 years were 22% and 19%, respectively.
      Treatment response and preradiotherapy carcinoembryonic antigen level were
      significant prognostic factors for local control and survival. Grade 3-5 toxicity
      occurred in 7 patients. Three patients had grade 5 toxicity, including radiation
      pneumonitis, a tracheoesophageal fistula, and hemoptysis. CONCLUSIONS: . Curative
      radiotherapy for isolated lung metastasis from colorectal cancer in patients who
      are medially inoperable or unsuitable for surgery results in long-term survival,
      comparable to surgical resection. Curative radiotherapy could be an effective and
      noninvasive alternative if dose-limiting toxicity is carefully considered,
      particularly in patients with bilateral or central lesions.

PMID- 23549002
TI  - Patterns of practice in the radiation therapy management of rectal cancer: survey
      of the Interregional Group Piedmont, Valle d'Aosta and Liguria of the
      "Associazione Italiana di Radioterapia Oncologica (AIRO)".
AB  - AIMS AND BACKGROUND: To report the survey about the main aspects on the use of
      radiotherapy for the treatment of rectal cancer in Piedmont and Liguria. METHODS
      AND STUDY DESIGN: Sixteen centers (11 from Piedmont and 5 from Liguria) received
      and answered by email a questionnaire data base about clinical and technical
      aspects of the treatment of rectal cancer. All data were incorporated in a single
      data base and analyzed. RESULTS: Data regarding 593 patients who received
      radiotherapy for rectal cancer during the year 2009 were collected and analyzed.
      Staging consisted in colonoscopy, thoracic and abdominal CT, pelvic MRI and
      endoscopic ultrasound. PET/CT was employed to complete staging and in the
      treatment planning in 12/16 centers (75%). Neoadjuvant radiotherapy was employed
      more frequently than adjuvant radiotherapy (50% vs 36.4%), using typically a
      total dose of 45 Gy with 1.8 Gy/fraction. Concurrent chemoradiation with 5
      fluorouracil or capecitabine was mainly employed in neoadjuvant and adjuvant
      settings, whereas oxaliplatin alone or in combination with 5-FU or capecitabine
      and leucovorin was commonly employed as the adjuvant agent. The median interval
      from neoadjuvant treatment to surgery was 7 weeks after long-course radiotherapy
      and 8 days after short-course radiotherapy. The pelvic total dose of 45 Gy in the
      adjuvant setting was the same in all the centers. Doses higher than 45 Gy were
      employed with a radical intent or in case of positive surgical margins.
      Hypofractionated regimens (2.5, 3 Gy to a total dose of 35-30 Gy) were used in
      the palliative setting. No relevant differences were observed in target volume
      definition and patient setup. Twenty-six patients (4.4%) developed grade 3 acute
      toxicity. Follow-up was scheduled in a similar way in all the centers.
      CONCLUSIONS: No relevant differences were found among the centers involved in the
      survey. The approach can help clinicians to address important clinical questions
      and to improve consistency and homogeneity of treatments.

PMID- 23549004
TI  - Dosimetric evaluation of critical organs at risk in mastectomized left-sided
      breast cancer radiotherapy using breath-hold technique.
AB  - AIMS AND BACKGROUND: The aim of the study was to evaluate the dosimetric impact
      of the active breathing control-moderate deep inspiration breath-hold (ABC-mDIBH)
      technique on normal tissue sparing in locally advanced left-sided breast cancer
      radiotherapy. METHODS AND STUDY DESIGN: Twenty-seven consecutive patients with
      left-sided locally advanced breast cancer referred to our department for adjuvant
      radiotherapy were enrolled in the study. Each patient was scanned at free
      breathing and ABC-mDIBH for radiation treatment planning. Two separate
      radiotherapy treatment plans were generated with and without ABC-mDIBH to
      investigate the dosimetric impact of ABC-mDIBH in breast cancer radiotherapy.
      RESULTS: Between June 2011 and February 2012, 27 consecutive patients with left
      sided locally advanced breast cancer referred to our department for adjuvant
      radiotherapy were enrolled in the study. Dose-volume parameters of left anterior
      descending coronary artery, lungs, heart, contralateral breast, esophagus and
      spinal cord were significantly reduced with the use of ABC-mDIBH (P <0.001).
      CONCLUSIONS: Our study revealed that the use of ABC-mDIBH in the practice of
      locally advanced mastectomized left-sided breast cancer radiotherapy improves
      normal tissue sparing with the expected potential of decreasing treatment-related
      morbidity and mortality. Moreover, the resultant reduction achieved with ABC in
      doses to the left anterior descending coronary artery, which plays a central role
      in cardiac perfusion, may have implications for decreasing the potential of
      radiation-induced cardiac morbidity and mortality.

PMID- 23549005
TI  - 125I brachytherapy for localized prostate cancer: a single institution
      experience.
AB  - AIMS AND BACKGROUND: To evaluate the clinical outcome of a cohort of localized
      prostate cancer patients treated with 125I permanent brachytherapy at the
      University of Turin. METHODS AND STUDY DESIGN: A retrospective analysis was
      carried out on 167 consecutive patients with early stage prostate adenocarcinoma
      who underwent 125I brachytherapy between January 2003 and December 2010. A
      minimum follow-up of >= 12 months was mandatory for inclusion. Biochemical
      disease-free survival (defined on the basis of the ASTRO definition and the ASTRO
      Phoenix definition) was chosen as the primary end point. Secondary end points
      were gastrointestinal and genitourinary toxicity (acute and late, defined
      according to the RTOG scale). RESULTS: With a median follow-up of 42 months
      (range, 13.5-90.7), biochemical disease-free survival at 3 and 5 years was
      respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and
      85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the
      ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35
      ng/ml) were the only factors affecting biochemical disease-free survival both on
      univariate (P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR
      0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients
      experienced >= grade 3 acute urinary toxicity and 5% >= grade 3 late urinary
      toxicity. Prior transurethral prostate resection was the only independent
      predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P =
      0.009). CONCLUSIONS: This mono-institutional series confirmed that brachytherapy
      is an effective and safe treatment modality for localized prostate cancer, with
      acceptable short- and long-term morbidity rates.

PMID- 23549006
TI  - Clinical significance of CD44 variants expression in colorectal cancer.
AB  - AIMS AND BACKGROUND: We designed the present study to observe CD44s and CD44v6
      expressions in colorectal cancer and evaluate their clinical value. METHODS:
      CD44s and CD44v6 expression in colorectal cancer tissues were examined by an
      immunohistochemical test. Survival analysis was performed with the Kaplan-Meier
      method, and the differences between the CD44-positive and -negative groups were
      evaluated with the logrank test. RESULTS: The positive rates of CD44s and CD44v6
      were 66.7% and 63.2%, respectively. There were significant associations between
      CD44s positive expression and Dukes' stage or tumor differentiation. There were
      significant associations between CD44v6 positive expression and tumor
      differentiation, Dukes' stage and lymph node metastasis. There was a significant
      difference in the 5-year survival rates between CD44v6-positive and CD44v6
      negative groups (52.78% and 80.95%, respectively), but not between CD44s-positive
      and CD44s-negative groups (55.26% and 78.95%, respectively). Multivariate
      analysis indicated that CD44v6 positive expression predicts a poor prognosis.
      CONCLUSIONS: CD44s and CD44v6 play important roles in the infiltration and
      metastasis of colorectal cancer. CD44v6 positive expression can be a predictor
      for a poor prognosis.

PMID- 23549007
TI  - Reappraisal of pretreatment carcinoembryonic antigen in patients with rectal
      cancer receiving preoperative chemoradiotherapy.
AB  - AIMS AND BACKGROUND: The pretreatment serum carcinoembryonic antigen (CEA) level
      is an independent prognostic factor in colorectal cancer. We aimed to investigate
      the significance of CEA as a prognostic or predictive factor in rectal cancer
      patients receiving preoperative chemoradiotherapy (CRT). METHODS AND STUDY
      DESIGN: In total, 609 patients with locally advanced (cStage II-III) mid to
      distal rectal cancer who underwent preoperative CRT and radical surgery between
      2001 and 2008 were analyzed retrospectively. Predictive factors for pathologic
      CRT response were determined using multivariate logistic regression. A prognostic
      factor analysis was performed using the log-rank test and Cox proportional
      hazards regression. RESULTS: Elevated CEA levels (>5 ng/mL) were observed in 201
      (33.0%) patients at diagnosis. Following preoperative CRT, downstaging (ypStage 0
      I) occurred in 255 (41.9%) patients, of whom 88 had pathologic complete tumor
      regression. Pretreatment CEA was significantly associated with pathologic CRT
      response in terms of downstaging and tumor regression grade, and was the most
      relevant predictive factor. After a median follow-up period of 60 months, the 5
      year disease-free and overall survival rates were 76.2% and 84.6%, respectively.
      Prognostic factors independently associated with recurrence or survival included
      ypStage, circumferential resection margin, and histologic grade. CONCLUSIONS: In
      patients with rectal cancer who received preoperative CRT, the pretreatment CEA
      level was a significant and independent predictor of pathologic CRT response.
      However, it may not be able to predict long-term outcomes independently of
      ypStage.

PMID- 23549008
TI  - Plasma osteopontin level as a diagnostic marker of hepatocellular carcinoma in
      patients with radiological evidence of focal hepatic lesions.
AB  - AIMS: Hepatocellular carcinoma is one of the most aggressive malignant tumors and
      has limited treatment options. Needle-guided biopsies have been utilized as a
      tool to diagnose malignant focal hepatic lesions. These techniques are
      discouraged because of their complications. Nowadays, alpha fetoprotein is the
      most widely used tumor marker for screening and diagnosis of hepatocellular
      carcinoma. Nevertheless, this marker has limitations. The diagnostic role of
      plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to
      detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions
      was evaluated in this study. SUBJECT AND METHODS: Eighty participants were
      recruited from the Egyptian National Liver Institute and were self-assigned to
      three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20),
      and controls (n = 20). Participants' plasma osteopontin and serum alpha
      fetoprotein levels were determined and were compared across the three groups.
      RESULTS: The discriminatory ability of plasma osteopontin for hepatocellular
      carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha
      fetoprotein were not correlated with each other. Neither the gender nor the age
      of the patients showed a significant association with plasma osteopontin level.
      CONCLUSION: Measuring plasma osteopontin level alone has no advantage over serum
      alpha fetoprotein in patients with focal hepatic lesions due to chronic liver
      disease.

PMID- 23549009
TI  - Analysis of HYAL3 gene mutations in Chinese lung squamous cell carcinoma
      patients.
AB  - PURPOSE: In a previous study, we found a hyaluronidase 3 (HYAL3) gene mutation in
      exon 2 at position 188 by genome sequencing in a lung squamous cell carcinoma
      patient. The mutation results in substitution of serine for alanine. The aim of
      the study was to screen the HYAL3 gene mutation in Chinese lung squamous cell
      carcinoma patients and explore the correlation between mutation of HYAL3 with
      clinical and pathological characteristics in lung squamous cell carcinoma
      patients in China. METHODS: We applied polymerase chain reaction to examine the
      HYAL3 gene mutations in cancer tissues and their adjacent normal tissues from 39
      cases of lung squamous cell carcinoma patients. RESULTS: 1) The incidence rate of
      HYAL3 mutation in 39 cases of lung squamous cell carcinoma was 10.26% (4/39) and
      none in adjacent normal lung tissues (0/39). 2) The mutations of HYAL3 in the 4
      cases were all heterozygous: 3 of them were located in exon 1 (G-T) and one in
      exon 2 (G-T). 3) Mutations of the HYAL3 gene were not correlated with the
      distribution of patient gender, age, tumor size, histological grade, smoking
      history, TNM stage or distant metastasis (P >0.05). The gene mutation was
      correlated with lymph node status (P = 0.044). CONCLUSION: Mutations of the HYAL3
      gene are rare in Chinese lung squamous cell carcinoma patients and might
      contribute to lymph node metastasis.

PMID- 23549010
TI  - Anticancer activities of anti-membrane antibodies against colon carcinoma cells
      undergoing chemotherapy.
AB  - AIMS AND BACKGROUND: Chemotherapy combined with target therapy using antibodies
      against tumor cell membrane antigens may greatly increase the survival of cancer
      patients. Similar to autoantigens in autoimmunity diseases, certain membrane
      components may be more heterogeneous and create new determinants of antigens or
      haptens after chemotherapy. The aim of the current study was to prepare anti
      membrane antibodies against colon carcinoma cells undergoing chemotherapy and
      examine their anticancer activities in vitro. METHODS: After the colon carcinoma
      cells were treated by mimic chemotherapy, the synthesized poly-lysine was used as
      a carrier to link the membrane antigen or hapten with the covalent bond of
      carbodiimide bridging. It was affirmed by fluorescence-activated cell sorting
      under laser confocal microscopy that the vaccine with poly-lysine membrane-linked
      cells with a covalent bond was successfully engineered. Then, the cognate mice
      were vaccinated, and the anti-membrane polyclonal antibodies were prepared and
      validated for their activities. RESULTS: The anti-membrane polyclonal antibodies
      were effectively induced and prepared. Folliculus lymphaticus were found
      significantly increased in vaccinated mice, and B lymphocyte proliferation was
      also intensively stimulated by vaccine and generating antibodies. The polyclonal
      antibodies, exhibiting minimal endotoxicity, displayed intensive sensitivity,
      high affinity and strong specificity. They also elicited apoptosis and necrosis
      for wild type colon carcinoma cells and offered synergistic effect to repress the
      chemotherapy-resistant tumor cells. CONCLUSIONS: The poly-lysine-linked membrane
      for colon carcinoma cells undergoing chemotherapy could produce the anti-membrane
      polyclonal antibodies (promising as novel antibody molecules for target therapy)
      and generate an effective immune attack on the surviving cancer cells.

PMID- 23549011
TI  - "PET scan contribution in chest tumors management: a systematic review for
      thoracic surgeons".

PMID- 23549012
TI  - The MaiSON Project (Italy). Developing integration strategies for oncology
      organizations/associations through a participatory approach.

PMID- 23549013
TI  - Malignant melanoma of the breast: a case report and review of the literature.
AB  - Primary breast melanoma is a rare entity that on routine histology may be
      mistaken for triple-negative breast cancer. A high degree of clinical suspicion
      is necessary to make this diagnosis. This case report describes the presentation
      and treatment of primary breast melanoma.

PMID- 23549014
TI  - Primary solitary extramedullary plasmacytoma involving the true vocal cords in a
      pregnant woman.
AB  - Primary solitary extramedullary plasmacytoma of the larynx involving the true
      vocal cords is an extremely rare entity. Extramedullary plasmacytoma has the
      potential to transform into multiple myeloma and mandates strict vigilance and
      routine follow-up. We describe such a case in a 29-year-old pregnant woman who
      presented with progressive hoarseness, dysphagia and intermittent respiratory
      difficulty. Fiberoptic laryngoscopy revealed a fleshy mass involving the
      posterior third of the true vocal cords, encroaching on the ventricle and false
      cords. Histopathology and immunohistochemistry revealed extramedullary
      plasmacytoma of a monoclonal nature. In spite of Bence Jones proteinuria and a
      rising serum beta 2-microglobulin level, a thorough search for metastasis and
      subsequent treatment with radiotherapy were delayed due to the patient's
      pregnancy. She is the youngest adult ever reported with primary solitary
      extramedullary plasmacytoma involving the true cords. Described for the first
      time in pregnancy, the relevant issues in management are highlighted.

PMID- 23549015
TI  - Can hepatocellular carcinoma (HCC) produce unconventional metastases? Four cases
      of extrahepatic HCC.
AB  - AIMS AND BACKGROUND: Extrahepatic spread of hepatocellular carcinoma (HCC)
      diagnosed during the clinical course of the disease is not frequent; however,
      with the prolonged survival of HCC patients, the incidence of extrahepatic
      metastases seems to be increasing. METHODS AND STUDY DESIGN: We present four
      unusual cases of extrahepatic metastasis from HCC: the first concerns a patient
      who underwent a liver transplantation for HCC with cirrhosis and three years
      later developed metastases in the lung and the left orbit; the second is that of
      a patient who developed an extraperitoneal pararectal metastasis; in the third
      case a large osteolytic lesion developed on the left iliac bone, and in the
      fourth case we found an isolated metastasis in the left mandible. RESULTS AND
      CONCLUSIONS: These cases offer important information related to the unusual
      biology of isolated metastases from HCC after successful treatment of the primary
      cancer.

PMID- 23549016
TI  - Severe thrombocytopenia related to long-term trastuzumab exposure.
AB  - Drug-induced immune thrombocytopenia may occur secondary to several
      chemotherapeutic agents or new targeted monoclonal antibodies, but
      thrombocytopenia induced by trastuzumab is a very rare occurrence. We report a
      case of severe thrombocytopenia related to the administration of trastuzumab six
      months after the first exposure.

PMID- 23549017
TI  - Primitive neuroectodermal tumor (PNET) as somatic-type malignancy arising from an
      extragonadal germ-cell tumor: clinical, pathological and molecular features of a
      case.
AB  - We report a rare case of a 34-year-old man with a right axillary mass. Ten years
      previously, he had been diagnosed with a right scapular nonseminomatous germ-cell
      tumor consisting of teratoma, completely resected without any further treatment.
      Presently he was found to have a metastatic malignant small round cell tumor
      consistent with a secondary somatic malignancy arising in the background of
      nonseminomatous germ-cell tumor, teratoma, yolk sac tumor, and primitive
      neuroectodermal tumor with distinct chromosome 22 translocation. Although the
      patient initially responded well to chemotherapy with etoposide, cisplatin,
      ifosfamide and mesna, he relapsed shortly after.

PMID- 23549018
TI  - Fatigue, quality of life, and mood states during chemotherapy in Italian cancer
      patients.
AB  - AIMS AND BACKGROUND: In cancer patients, fatigue interferes with the individual's
      functioning and quality of life (QoL). We investigated the association between
      fatigue and the main QoL dimensions and mood states as well as the main
      sociodemographic and clinical variables. METHODS: A total of 105 inpatients
      undergoing chemotherapy were administered the Revised Piper Fatigue Scale and the
      EORTC QLQ-C30 and POMS questionnaires, along with a form for collecting personal
      and clinical data. RESULTS: Compared with patients reporting lower fatigue
      levels, patients with higher levels showed worse functioning (P <0.001) in every
      QoL domain (i.e., physical, role, emotional, social, cognitive functioning, pain,
      and general health) as well as in the assessed mood states (depression-dejection,
      tension-anxiety, confusion-bewilderment). Moreover, both QoL and mood states in
      the subgroup reporting intermediate fatigue levels were worse than those of the
      subgroup with lower fatigue levels (P <0.02), except for emotional functioning,
      general health and QoL, and tension-anxiety. In addition, fatigue was
      significantly associated with gender, age, education, performance status, but not
      with marital status, survival rate of cancer type, and current chemotherapy
      cycle. CONCLUSIONS: The associations observed between fatigue, the main QoL
      domains, and negative mood states call for further active interventions to
      prevent and reduce fatigue.

PMID- 23549019
TI  - Gefitinib in non-small cell lung carcinoma: a case report of an unusual side
      effect and complete response in advanced disease.
AB  - Gefitinib is a tyrosine kinase inhibitor, indicated in advanced non-small cell
      lung cancer in all lines of treatment for patients harboring EGFR mutations. It
      has a favorable toxicity profile but may induce unexpected adverse effects, such
      as an infiammatory reaction in the bladder. We report a rare case of hemorrhagic
      cystitis, an unusual side effect, in a patient with non-small cell lung cancer
      treated with gefitinib, which did not compromise the clinical response.

PMID- 23549020
TI  - Leptomeningeal metastasis from prostate cancer.
AB  - AIMS AND BACKGROUND: Metastatic prostate carcinoma commonly involves bones and
      extrapelvic lymph nodes, with occasional visceral deposits. Central nervous
      system involvement is unusual and particularly the occurrence of leptomeningeal
      metastasis (LM) is extremely rare, with few cases described in the medical
      literature. The clinical presentation is characterized by multifocal neurological
      deficit and the prognosis is generally dismal, with survival ranging between 3
      and 6 months. We report on a patient affected by LM due to prostate cancer who
      was treated with a combined-modality approach consisting of sequential
      chemotherapy and radiotherapy. METHODS: A 70-year-old man was referred to our
      group for cognitive mental disorder, left-sided frontal headache and nausea; the
      patient had a previous history of metastatic prostate cancer. LM was diagnosed
      neuroradiologically with brain MRI and evidence of a detectable level of PSA in
      the cerebrospinal fluid. He was treated with docetaxel and prednisone for 3
      cycles followed by external beam radiotherapy (EBRT) to the whole brain to a
      total dose of 30 Gy in 10 fractions with a simultaneous integrated boost to the
      macroscopic disease (total dose of 35 Gy in 10 fractions). No acute toxicity was
      observed. RESULTS: A substantial clinical response was obtained after EBRT with
      neurological improvement and radiologically stable disease at post-treatment
      imaging until 10 weeks after radiation. The patient died of sudden general
      condition deterioration 3 months after EBRT. CONCLUSION: Since LM derived from
      prostate cancer is likely to become a more common clinical event, such patients
      would need to be included in clinical trials evaluating new therapeutic
      approaches, considering that the current treatment strategies have been shown to
      be rather ineffective.

PMID- 23549021
TI  - Attachment of an anti-MUC1 monoclonal antibody to 5-FU loaded BSA nanoparticles
      for active targeting of breast cancer cells.
AB  - With PR81 as a murine monoclonal antibody (mAb) that was prepared against the
      human breast cancer, the MUC1 receptor specific targeting is possible. In this
      study, PR81-conjugated bovine serum albumin (BSA) nanoparticles loaded with
      anticancer drug 5-fluorouracil (5-FU) were developed. Enzyme linked immunosorbant
      assay (ELISA) results showed high immunoreactivity of PR81 mAb conjugated to
      nanoparticles towards MUC1 related peptide or native cancerous MUC1 and almost no
      cross-reaction to non-specific proteins. In vitro experiments were performed to
      determine the ability of this new drug delivery system on overcoming MCF-7 breast
      cancer cells in comparison with four other systems. The results revealed that
      these cell-type specific drug loaded nanoparticles could achieve more cell death
      as compared to when the 5-FU was used with no carriers. Stability studies of
      produced drug delivery system proved high immunoreactivity of conjugated PR81
      even after 11 days of storage in room temperature.

PMID- 23549022
TI  - Development and characterization of monoclonal antibodies against human CD20 in
      Balb/c mice.
AB  - BACKGROUND: Targeting CD20 antigen on B-lymphocytes provides good opportunity for
      management of the target cells in patients with B-cell malignancies. By the
      advent of hybridoma technology, monoclonal antibodies applications exert
      extensive changes in medical fields such as diagnosis, treatment and
      purification. OBJECTIVE: The prim aim of this study was to produce monoclonal
      antibody against CD20 for exploitation in diagnosis. METHODS: In this study,
      Balb/c mice were immunized with two peptides from extracellular domain of CD20.
      Poly Ethylene Glycol (PEG) fused spleen cells of the most immune mouse with SP2/0
      (myeloma cells). Supernatant of hybridoma cells were screened for detection of
      antibody by ELISA. The desired clones were selected for limiting dilution (L.D).
      Afterward, specificity and cross reactivity of these antibodies were determined
      by immunological assay such as ELISA and western blot analysis (WB) and
      Immunofluorescence. Large scale of monoclonal antibodies was produced by ascetic
      fluid method. Monoclonal antibody was purified by chromatography then confirmed
      by SDS-PAGE. RESULTS: In this study, between five positive clone wells, 3 clones
      were chosen for limiting dilution. Limiting dilution product was one monoclone
      with absorbance about 2. CONCLUSIONS: These results indicate that such monoclonal
      antibodies against CD20 can be used in diagnosis of CD20 in the cells surface.

PMID- 23549023
TI  - Clonal analysis of human anti-V3 monoclonal antibodies selected by a V3 tetramer.
AB  - The production of human monoclonal antibodies (mAbs) has been improved recently
      using the single B cell and PCR technology. A number of new anti-HIV-1 mAbs
      directed to various epitopes were produced by selecting single B cells from HIV
      positive individuals using the HIV-1 envelope (Env) proteins, and we tested
      whether the peptide can select B cells specific to a particular Env epitope.
      Using the fluorescently-labeled peptide tetramer representative of the V3 loop of
      HIV-1 Env gp120 for staining the B cells derived from one HIV-1 infected donor,
      four clonal human mAbs were produced with specificity to the V3 region. The
      clonality of the four V3 mAbs was based on the usage of the same immunoglobulin
      genes and almost identical sequence of CDRs. The amino acid changes were present
      only in the framework and, possibly, they could be related to the differences
      observed in the relative affinity binding of these four mAbs to V3 antigen. One
      representative V3 mAb displayed very potent neutralizing activity to one of two
      viruses tested. This study shows the feasibility of utilizing a peptide tetramer
      to select epitope-specific B cells and produce mAbs.

PMID- 23549028
TI  - Efficacy of recombinant allergens for diagnosis of cockroach allergy in patients
      with asthma and/or rhinitis.
AB  - BACKGROUND: Immunoglobulin E (IgE) reactivity to individual allergens among
      cockroach-allergic patients has revealed wide variability. The aim of this study
      was to assess the effectiveness of recombinant cockroach allergens for skin
      testing, and to determine sensitization profiles among cockroach-allergic
      patients living in Brazil. METHODS: Fifty-seven cockroach-allergic patients with
      asthma and/or rhinitis were recruited. Skin testing with recombinant (r)
      allergens from Periplaneta americana (rPer a 1 and rPer a 7) and Blattella
      germanica (rBla g 2, rBla g 4 and rBla g 5) were performed at 10 MUg/ml and 5
      MUg/ml (rPer a 1). IgE antibodies to rPer a 7 and rPer a 1 were quantitated by
      ELISA. RESULTS: Of 57 patients tested, 3 (5.3%), 24 (42.1%), 4 (7%), 3 (5.3%) and
      4 (7%) showed positive reactions to rPer a 1, rPer a 7, rBla g 2, rBla g 4 and
      rBla g 5, respectively. Twenty-eight patients (49.1%) had positive tests to at
      least one allergen. In keeping with skin test results, 31/57 patients (54.4%) and
      5/55 patients (9%) had detectable IgE to rPer a 7 and rPer a 1, respectively.
      Levels of IgE to rPer a 7 were higher in patients with positive tests to rPer a 7
      than those with negative tests (geometric mean 13.2 and 1.8 IU/ml, p < 0.05).
      There was good concordance of results of skin tests and measurements of serum IgE
      to rPer a 7. CONCLUSION: IgE reactivity to rPer a 7 (P. americana tropomyosin)
      was dominant among patients in Brazil. However, 50% of the patients did not
      present reactivity to any of the recombinant allergens tested.

PMID- 23549027
TI  - Gut microbial diversity is reduced and is associated with colonic inflammation in
      a piglet model of short bowel syndrome.
AB  - BACKGROUND AND OBJECTIVES: Following small bowel resection (SBR), the luminal
      environment is altered, which contributes to clinical manifestations of short
      bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial
      overgrowth. However, the impact of SBR on the colon has not been well-defined.
      The aims of this study were to characterize the colonic microbiota following SBR
      and to assess the impact of SBR on mucosal inflammation in the colon. RESULTS:
      Analysis of the colonic microbiota demonstrated that there was a significant
      level of dysbiosis both two and six weeks post-SBR, particularly in the phylum
      Firmicutes, coupled with a decrease in overall bacterial diversity in the colon.
      This decrease in diversity was associated with an increase in colonic
      inflammation six weeks post-surgery. METHODS: Female (4-week old) piglets (5
      6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional
      analysis of the colonic microbiota was performed by high-throughput sequencing,
      two- and six-weeks post-surgery. The gene expression of the pro-inflammatory
      cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-18 and tumor necrosis factor
      (TNF)-alpha in the colonic mucosa was assessed by qRT-PCR and the number of
      macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the
      colonic epithelium were quantified by immunohistochemistry. CONCLUSIONS: SBR
      significantly decreased the diversity of the colonic microbiota and this was
      associated with an increase in colonic mucosal inflammation. This study supports
      the hypothesis that SBR has a significant impact on the colon and that this may
      play an important role in defining clinical outcome.

PMID- 23549029
TI  - [Foreward].

PMID- 23549030
TI  - [Status of clinical trials in oncology--2013 and onwards].
AB  - Clinical trials connect basic science with patient care. They form the backbone
      of evidence-based medicine and clinical guidelines. The unprecedented
      implementation of new methods in oncology over the past 40 years has only been
      possible on the basis of multiple well-organized clinical study groups. The
      continued existence of these study groups in their current multitude is in
      danger. Far-reaching changes in the legal framework, underfunding, new
      definitions of patient-related outcome and shifts in the organization of cancer
      patient care ask for critical reappraisal and new concepts.

PMID- 23549031
TI  - [The necessity of independent clinical trials from the perspective of the
      Institute of Quality and Efficiency in Health Care].
AB  - The results of clinical, preferably randomized controlled trials (RCTs) form the
      backbone of drug approval decisions and benefit assessments of medical
      interventions. Whereas drug approval studies often answer at least some of the
      relevant questions posed in a benefit assessment, the situation is totally
      different for non-drug treatments and diagnostic tests, as the requirements for
      market entry are not as high in these fields. Overall it must be concluded that
      in the past and up to the present time there have been insufficient (financial)
      incentives for manufacturers or providers of medical interventions to conduct
      clinical trials concerning patient-relevant benefits both in the field of drugs
      and particularly in non-drug interventions. This has led to a lack of studies
      that, in an appropriate comparison with sufficient certainty of results, provide
      data on the patient-relevant benefits or added benefits of a medical
      intervention. In this context, it is secondary whether these are 'independent'
      studies, the more so as 'dependencies' can never be excluded and can become
      especially problematic in cases where they are not easily recognized by
      declaration of sponsorship. The Institute of Quality and Efficiency in Health
      Care (IQWiG) is willing to promote the creation of appropriate funding
      opportunities for important study projects of clinical research groups fulfilling
      the criteria for a high-quality patient-oriented clinical trial on a relevant
      research question, and is currently doing so together with interested parties.

PMID- 23549032
TI  - [New drugs in oncology--features of clinical trials for market authorisation and
      arguments for the rapid implementation of independent clinical trials following
      approval].
AB  - The market authorisation or extension of indication for all oncology drugs in
      Europe is now based on Regulation (EC) No. 726/2004, a centralised procedure of
      the European Medicines Agency (EMA). Studies in recent years have highlighted
      deficiencies in pivotal studies. For example, the requirements of the EMA are not
      always consistently followed and studies are stopped prematurely after only
      interim analysis that at this time point shows improved efficacy with regard to
      the comparator arm. Our current analysis of the European Assessment Reports
      (reporting period: 01/01/2009 to 08/13/2012) on 29 drugs for 39 oncology
      indications shows that the quality of the trials for market authorisation has
      improved in several respects. Primary endpoints recommended by the EMA and the
      Food and Drug Administration (FDA) such as overall survival and progression-free
      survival are used, and only one study was conducted as a phase II trial with no
      comparator arm. In contrast, oncology drugs that are approved for the treatment
      of rare diseases (orphan drugs) are based on small studies which are often
      carried out without blinding, are not randomised and investigate surrogate
      endpoints. To answer patient-relevant issues following market authorisation, it
      is necessary to conduct independent clinical studies. Increased public funding
      needs to be provided and bureaucratic hurdles have to be reduced. Only this will
      permit a more efficient use of limited health care resources and allow to improve
      the quality of care for cancer patients.

PMID- 23549033
TI  - [Focus on academic multicenter trials: impact of the German drug law on
      hematological/oncological therapy optimization trials].
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of legal
      regulations for clinical trials on study centers participating in investigator
      initiated trials (IITs) in the field of hematology/oncology. METHOD:
      Questionnaires were sent out to the heads of hematology-oncology study centers.
      RESULTS: Medical units participating in IITs have a good infrastructure and
      extensive experience in clinical trials. Depending on indication, a high
      proportion of patients have been treated in studies with the purpose to improve
      outcome. However, 35% of the responders will reduce their participation in IITs
      in the future due to a lack of financial support for staff involved in the
      extensive organizational tasks. CONCLUSIONS: The widely recognized research field
      in therapy optimization trials in hematology and oncology in Germany is at risk.
      This will have negative effects on the patients as highly sophisticated protocols
      will no longer be initiated in several study centers, resulting in the loss of
      valuable data for the improvement of patient therapy and outcome. To stop this
      development, legislators as well as regulatory authorities and health insurances
      need to make the necessary changes in the legal framework.

PMID- 23549034
TI  - [Application for academic multicenter studies at German ethical review boards].
AB  - Before the start of a clinical trial, approval by the responsible institutional
      ethical review board (IRB) is required. In Germany, nearly 50 independent IRBs
      may be responsible for the different participating sites of a multicenter study.
      In trials for rare diseases, the participation of many centers is required.
      Therefore, the application procedure for academic multicenter trials in malignant
      hematologic diseases is often a bureaucratic nightmare. Different aspects of IRB
      application and possible approaches for improvement are presented.

PMID- 23549035
TI  - [QualiPRO: online database to facilitate study participation for investigators,
      study sites and coordinating centers].
AB  - Academic non-commercial trials are of substantial relevance for both patient care
      and progress in clinical research. Since the 12th amendment of the German drug
      law, applications for the initiation of clinical trials at the ethical review
      boards are much more cost- and time-intensive, particularly for multicenter
      therapy optimization trials (TOS). To activate a trial, for, e.g., 51 ethical
      review boards, current curricula vitae (CVs) and certificates on good clinical
      practice (GCP) and regulations have to be provided for all investigators. After
      the new amendment of the German drug law in 2012, the process remains complex
      while the responsibility of the team eligibility has now been transferred to the
      main investigator at the study site. Therefore, the online database 'QualiPRO'
      was developed, free of charge and widely accessible for the investigators, their
      clinical trial units and the coordinating centers of the TOS. Its features ease
      the process to generate and provide data on the clinical trial activities of any
      investigator and team member. The database content and architecture follows
      ethical review board recommendations and the Good Clinical Practice (GCP) of the
      International Conference on Harmonisation (ICH). After registration of the unit
      and membership of the team, study staff' members are able to enter and edit data
      and to print a 'trial' CV. CVs, GCP certificates, licences to practice medicine
      and more can be uploaded, and, after consent of the investigators, are available
      to the coordinating centers of TOS. In addition, QualiPRO is an instrument for
      directors of hospital departments or group leaders to efficiently collect and
      locally display data on their study activities and on the training status of
      their staff.

PMID- 23549036
TI  - [The economic dilemma].
AB  - Clinical studies have been situated very well in Germany during the last 10
      years; oncologists in practices and clinics are highly motivated. However, the
      financing of clinical trials is desolate so that disillusionment spreads in many
      centers. This paper would like to give some impetus to the discussion on better
      and more adequate financing. Facts and backgrounds concerning unsatisfactory
      financing of clinical trials are demonstrated; costs are analyzed in a detailed
      way. It seems to be very important to establish tools for a better calculation of
      costs. First approaches have been defined.

PMID- 23549037
TI  - ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive
      factors in advanced NSCLC treated with or without cisplatin.
AB  - BACKGROUND: The FAST was a factorial trial in first-line treatment of advanced
      non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin
      with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1
      expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was
      examined. METHODS: Patients were randomised to receive treatment with or without
      cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1
      (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene
      polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination
      assay. RESULTS: Tumour samples were available from 110 of 433 patients enrolled:
      54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative
      patients had better response rate (P=0.004), progression-free survival (P=0.023)
      and overall survival (P=0.012) compared with positive ones, with no statistically
      significant treatment interaction. The BRCA1-positive patients showed numerically
      better outcomes, although not statistically significant, with no treatment
      interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype
      evidenced a potential prognostic role (P=0.036). CONCLUSION: This study confirms
      the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in
      advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was
      shown to be a specific predictive factor of cisplatin efficacy.

PMID- 23549038
TI  - Risk of cancer following primary total hip replacement or primary resurfacing
      arthroplasty of the hip: a retrospective cohort study in Scotland.
AB  - BACKGROUND: Release and dispersion of particles arising from corrosion and wear
      of total hip arthroplasty (THA) components has raised concerns about a possible
      increased risk of cancer. Concerns have been heightened by a recent revival in
      the use of metal-on-metal (MoM) hip prostheses. METHODS: From a linked database
      of hospital discharge, cancer registration, and mortality records, we selected a
      cohort of patients who underwent primary THA (1990-2009) or primary resurfacing
      arthroplasty (mainly 2000-2009) in Scotland, with follow-up to the end of 2010.
      Available operation codes did not enable us to distinguish MoM THAs. Indirectly
      standardised incidence ratios (SIRs) were calculated for selected cancers with
      standardisation for age, sex, deprivation, and calendar period. RESULTS: The
      study cohort included 71 990 patients yielding 547 001 person-years at risk
      (PYAR) and 13 946 cancers diagnosed during follow-up. For the total period of
      observation combined, the risks of all cancers (SIR: 1.05; 95% CI: confidence
      interval 1.04-1.07), prostate cancer (SIR: 1.07; 95% CI: 1.01-1.14), and multiple
      myeloma (SIR: 1.22; 95% CI: 1.06-1.41) were increased. These modest increases in
      risk emerged in the context of effectively multiple tests of statistical
      significance, and may reflect inadequate adjustment for confounding factors. For
      1317 patients undergoing primary resurfacing arthroplasty between 2000 and 2009
      (PYAR=5698), the SIR for all cancers (n=39) was 1.23 (95% CI: 0.87-1.68).
      CONCLUSION: In the context of previous research, these results do not suggest a
      major cause for concern. However, the duration of follow-up of patients receiving
      recently introduced, new-generation MoM prostheses is too short to rule out a
      genuinely increased risk of cancer entirely.

PMID- 23549039
TI  - Unresolved problems with distress screening.

PMID- 23549040
TI  - Central nervous system infections among individuals with and without end-stage
      renal disease.
AB  - OBJECTIVES: Individuals with immunodeficiencies are at increased risk of central
      nervous system (CNS) infections. Data are limited on the risk of CNS infections
      in patients with end-stage renal disease (ESRD). METHODS: We conducted a
      population-based, nationwide cohort study among ESRD patients from 1990 to 2009.
      Data on ESRD patients was obtained from the Danish Nephrology Registry database.
      Each ESRD patient was matched with up to 19 population controls. Using the
      National Hospital Registry we identified hospital admissions with CNS infection
      as primary discharge diagnosis. RESULTS: The study included 13,374 ESRD patients
      and 245,397 population controls, providing 67,012 person-years and 2,237,237
      person-years of observation, respectively. The overall incidence rate (IR) of
      first-time hospitalisation for CNS infection was 149 per 100,000 person-years
      (95%-confidence interval [CI], 123-181) among ESRD patients. The IR of CNS
      infection was comparable among dialysis and transplant patients. Compared to
      population controls, the incidence rate-ratio of first CNS infection was 5.58
      (95%-CI, 4.47-6.91) for ESRD patients in general. The 30-day mortality following
      hospitalisation for CNS infections was 21% (95%-CI, 14-30) among ESRD patients
      and 13% (95%-CI, 10-16) among population controls. CONCLUSIONS: ESRD patients
      have considerable excess risk and mortality from CNS infections, which is of
      great clinical and public health concern.

PMID- 23549041
TI  - Predictors of visual outcome in eyes with choroidal neovascularization secondary
      to age related macular degeneration treated with intravitreal bevacizumab
      monotherapy.
AB  - AIM: To evaluate the predictors of visual improvement in eyes with naive
      choroidal neovascularization secondary to age-related macular degeneration (CNV 
      AMD) treated with intravitreal bevacizumab (IVB) monotherapy. METHODS: Fifty eyes
      with naive CNV- AMD with pretreatment best-corrected visual acuity (BCVA) better
      than 20/200 and treated with IVB monotherapy were evaluated. Several variables
      including age, sex, pre-treatment BCVA, CNV type and lesion size on fluorescein
      angiogram as well as SD-OCT parameters including pre-treatment central macular
      thickness (CMT), inner-segment/outer-segment (IS/OS) junction integrity, and
      external limiting membrane (ELM) integrity were analyzed to predict visual
      outcome. RESULTS: On univariate regression, pretreatment ELM damage was
      associated with less visual improvement after treatment (P=0.0145). However, ELM
      damage predicted only 10% of the visual outcome. On multivariate regression,
      pretreatment BCVA, IS/OS junction, and ELM integrity on SD-OCT were the
      significant predictors for the treatment effect and together predicted 37% of
      visual improvement. CONCLUSION: Pretreatment BCVA, ELM and IS/OS junction
      integrity on SD-OCT are of significant value in predicting the visual improvement
      in naive wet AMD patients treated with IVB monotherapy.

PMID- 23549042
TI  - Nursing informatics in clinical practice in China.
AB  - Nursing informatics has become a useful tool for worldwide patient care and
      management; however, its implementation greatly varies according to specialty,
      healthcare setting, and nation. The purpose of this study was to determine
      nursing informatics implementation in Qiqihar, China. Questionnaires evaluating
      the advantages and disadvantages of nursing informatics implementation and
      hospital information system knowledge were distributed among three hospitals in
      Qiqihar. A convenient sample of 50 nurses from each hospital (total N = 150) was
      selected to participate in this study. Responses indicated that despite a
      relatively brief training period, nursing informatics was adequately implemented,
      and nurses were knowledgeable about hospital information systems. Respondents
      identified several key advantages of nursing informatics implementation,
      particularly its usefulness in aiding patient care for data management. Finally,
      respondents identified hospital information system instability as a major
      obstacle to nursing informatics implementation. Our study results may help
      clinical nursing practitioners improve their technology skills and help nursing
      administrators improve information programs. These findings provide an important
      reference for both nursing informatics practice and further studies.

PMID- 23549043
TI  - Mycobacterium smegmatis Lhr Is a DNA-dependent ATPase and a 3'-to-5' DNA
      translocase and helicase that prefers to unwind 3'-tailed RNA:DNA hybrids.
AB  - We are interested in the distinctive roster of helicases of Mycobacterium, a
      genus of the phylum Actinobacteria that includes the human pathogen Mycobacterium
      tuberculosis and its avirulent relative Mycobacterium smegmatis. Here, we
      identify and characterize M. smegmatis Lhr as the exemplar of a novel clade of
      superfamily II helicases, by virtue of its biochemical specificities and
      signature domain organization. Lhr is a 1507-amino acid monomeric nucleic acid
      dependent ATPase that uses the energy of ATP hydrolysis to drive unidirectional
      3'-to-5' translocation along single strand DNA and to unwind duplexes en route.
      The ATPase is more active in the presence of calcium than magnesium. ATP
      hydrolysis is triggered by either single strand DNA or single strand RNA, yet the
      apparent affinity for a DNA activator is 11-fold higher than for an RNA strand of
      identical size and nucleobase sequence. Lhr is 8-fold better at unwinding an
      RNA:DNA hybrid than it is at displacing a DNA:DNA duplex of identical nucleobase
      sequence. The truncated derivative Lhr-(1-856) is an autonomous ATPase, 3'-to-5'
      translocase, and RNA:DNA helicase. Lhr-(1-856) is 100-fold better RNA:DNA
      helicase than DNA:DNA helicase. Lhr homologs are found in bacteria representing
      eight different phyla, being especially prevalent in Actinobacteria (including M.
      tuberculosis) and Proteobacteria (including Escherichia coli).

PMID- 23549045
TI  - The Prostate Cancer Patient Had Higher C-Reactive Protein Than BPH Patient.
AB  - PURPOSE: C-reactive protein (CRP) is a general marker for inflammation and it has
      been associated with prostate cancer. We hypothesized that a correlation may
      exist between CRP and prostate cancer in patients undergoing transrectal biopsy
      of the prostate because of rising prostate-specific antigen (PSA) levels.
      MATERIALS AND METHODS: From January 2009 to March 2012, we retrospectively
      reviewed 710 patients who visited our urology department and were diagnosed as
      having a PSA value over 4.0 ng/mL. Patients with acute infections, rheumatoid
      arthritis, gout, asthma, chronic lung disease, myocardial infarction, or apoplexy
      and those who had taken nonsteroidal anti-inflammatory drugs were exempted from
      the research because these variables could have impacted CRP. After we applied
      the exclusion criteria, we selected 63 patients with prostate cancer and 140
      patients with benign prostatic hyperplasia (BPH). RESULTS: A total of 203
      patients were observed: 140 patients had BPH, and 63 patients had prostate
      cancer. Prostate cancer patients were divided into two groups by tumor-node
      metastasis classification. The patients below T2 were group A, and those above T3
      were group B. The natural logarithm of C-reactive protein (lnCRP) differed
      between the BPH group and the prostate cancer group. The lnCRP also differed
      between the BPH group and prostate cancer groups A and B (p<0.05). CONCLUSIONS:
      The serum CRP level of the prostate cancer group was higher than that of the BPH
      group. Inflammation may be correlated with prostate cancer according to the serum
      CRP level.

PMID- 23549044
TI  - Dbf4 and Cdc7 proteins promote DNA replication through interactions with distinct
      Mcm2-7 protein subunits.
AB  - The essential cell cycle target of the Dbf4/Cdc7 kinase (DDK) is the Mcm2-7
      helicase complex. Although Mcm4 has been identified as the critical DDK
      phosphorylation target for DNA replication, it is not well understood which of
      the six Mcm2-7 subunits actually mediate(s) docking of this kinase complex. We
      systematically examined the interaction between each Mcm2-7 subunit with Dbf4 and
      Cdc7 through two-hybrid and co-immunoprecipitation analyses. Strikingly different
      binding patterns were observed, as Dbf4 interacted most strongly with Mcm2,
      whereas Cdc7 displayed association with both Mcm4 and Mcm5. We identified an N
      terminal Mcm2 region required for interaction with Dbf4. Cells expressing either
      an Mcm2 mutant lacking this docking domain (Mcm2DeltaDDD) or an Mcm4 mutant
      lacking a previously identified DDK docking domain (Mcm4DeltaDDD) displayed
      modest DNA replication and growth defects. In contrast, combining these two
      mutations resulted in synthetic lethality, suggesting that Mcm2 and Mcm4 play
      overlapping roles in the association of DDK with MCM rings at replication
      origins. Consistent with this model, growth inhibition could be induced in
      Mcm4DeltaDDD cells through Mcm2 overexpression as a means of titrating the Dbf4
      MCM ring interaction. This growth inhibition was exacerbated by exposing the
      cells to either hydroxyurea or methyl methanesulfonate, lending support for a DDK
      role in stabilizing or restarting replication forks under S phase checkpoint
      conditions. Finally, constitutive overexpression of each individual MCM subunit
      was examined, and genotoxic sensitivity was found to be specific to Mcm2 or Mcm4
      overexpression, further pointing to the importance of the DDK-MCM ring
      interaction.

PMID- 23549046
TI  - Hirayama disease in children from mainland of China.
AB  - Hirayama disease is characterized by asymmetrical focal weakness and atrophy of
      the distal upper limbs with onset in the teens and early 20s. This retrospective
      study aims to review clinical features of the children (onset before the age of
      18 years) with Hirayama disease from mainland of China. Sixty-five children who
      fulfilled the clinical criteria for Hirayama disease were enrolled. The mean age
      of onset was 15.7 years, 3.3 years later than the peak age for the normal growth
      curve. Electrophysiology studies showed chronic denervation changes in C7-T1
      segments with normal sensory nerve conduction. Flexion cervical magnetic
      resonance imaging (MRI) showed forward shifting of the posterior dural sac and
      engorgement of the posterior epidural venous plexus. Therapeutic intervention
      with cervical collar can induce a premature arrest of disease progression.
      Knowledge and awareness of Hirayama disease will facilitate diagnosis and
      therapeutic intervention in its early stages.

PMID- 23549048
TI  - Emotion-focused therapy and dietary counseling for obese patients with binge
      eating disorder: a propensity score-adjusted study.

PMID- 23549047
TI  - Recurrent digital infections and osteomyelitis in monozygotic twins with
      congenital analgesia and compulsive onychophagia.
AB  - Congenital insensitivity to pain is a rare sensory neuropathy that manifests with
      multiple and recurrent injuries secondary to a lack of negative pain stimuli.
      When present with compulsive onychophagia, prompt recognition and behavioral
      management to prevent chronic digital infection or amputation is imperative. We
      present the case of two 7 year-old monozygotic twins that presented with
      congenital insensitivity to pain and compulsive onychophagia without directed
      parental counseling or behavioral modification strategies. The presenting child
      was noted to have an acute digital felon and osteomyelitis of several distal
      phalanges, and the sister had a similar history with distal phalangeal
      amputations. The occurrence of these overlapping disorders in monozygotic twins
      has not been previously reported, however, patient and parental education with
      behavioral modifications of injurious and compulsive behavior is the cornerstone
      of management. In addition, we have provided a review of the diagnosis for
      clinical differentiation. 

PMID- 23549050
TI  - Effects of long-duration space flights on characteristics of the vertical gaze
      fixation reaction.
AB  - The aim of the study was to examine effects of long-duration exposure to
      weightlessness on characteristics of the vertical gaze fixation reaction (GFR).
      The subjects were to perform the target acquisition task on visual stimuli that
      appeared at a distance of 16 deg. up- and down from the primary position in a
      random order. Experiments were performed before launch, during flight and after
      landing. Before flight time of gaze fixation reaction did not exceed 650 ms.
      During space flight (SF) it extended up to 900-1000 ms and more. The velocities
      of head movement in space decreased, but the velocities of eye counterrotation
      decreased to a lesser degree. This difference resulted in sharp increase of
      vertical vestibular ocular reflex (VOR) gain (up to 4.3 values in one of the
      cosmonauts) during the 1st month of flight; further it decreased reaching the
      values of 0.5-0.7 on the 5th month of SF. After landing vertical VOR gain
      increased greatly again. These results in the vertical axis are in agreement with
      the data of Kozlovskaya et al., which showed in experiments with monkeys that
      horizontal VOR gain increased together with redundant inadequate responses of
      vestibular nucleus on vestibular stimulation and that in the course of adaptation
      to these conditions central nervous system inhibited vestibular input from the
      motor control system.

PMID- 23549051
TI  - Eye movements and motion perception during off-vertical axis rotation after
      spaceflight.
AB  - Constant velocity off-vertical axis rotation (OVAR) provides dynamic linear
      acceleration stimuli that can be used to assess otolith function. Eight
      astronauts were rotated in darkness about their longitudinal axis 20 degrees  off
      vertical at low (0.125 Hz) and high (0.5 Hz) frequencies and their responses were
      compared before and after spaceflight. Eye movements were recorded using infrared
      videography and perceived motion was evaluated using a joystick with four degrees
      of freedom - pitch and roll tilt, front-back and lateral translation. Low
      frequency OVAR generates tilt otolith-induced responses - modulation of ocular
      counter-roll and counter-pitch with perceived conical motion path - whereas high
      frequency OVAR generates translational otolith-induced responses - modulation of
      horizontal and vergence slow phase velocity with perceived cylindrical motion
      path. While there were transient changes in the amplitude of the translational
      ocular responses on landing day, there were no major changes in the tilt ocular
      reflexes after adaptation to weightlessness. However, there was an increase in
      sensitivity to motion perception after spaceflight. Direct comparisons of pre-
      and postflight stimuli suggested that OVAR on landing day was less provocative of
      motion sickness than before spaceflight. These results confirm that some otolith
      reflexes elicited during passive motion may not be altered by short-duration
      spaceflight - or may readapt very quickly - and that the resolution of sensory
      conflict associated with postflight recovery involves higher-order neural
      processes.

PMID- 23549052
TI  - Validation of centrifugation as a countermeasure for otolith deconditioning
      during spaceflight: preliminary data of the ESA SPIN study.
AB  - In the framework of further space exploration, countermeasures to combat the
      drawbacks of human space flights are essential. The present study focuses on the
      influence of microgravity on the otolith-ocular reflex and aims to test the
      hypothesis of artificial gravity being an adequate countermeasure for the
      deconditioning of the aforementioned reflex. The so-called SPIN study,
      commissioned by the European Space Agency, can be considered as a control
      experiment in the broad sense for the Neurolab mission (STS-90) during which 4
      crewmembers of the space shuttle were subjected to in-flight centrifugation on
      the visual and vestibular investigation system (VVIS). After their nearly 16-day
      mission, they did not suffer from orthostatic intolerance and spatial
      disorientation. In addition, the relevant parameters of the otolith-ocular
      interaction remained unaffected. For this study cosmonauts from a long duration
      stay in the International Space Station that were not centrifuged in-flight were
      tested on the VVIS (1 g centripetal interaural acceleration) on 6 different days.
      Three measurements were taken about 1.5-2 months prior to launch and 3 were taken
      at 1, 4 and 9 days after return from space. Ocular counter-rolling was measured
      before, during and after rotation on the VVIS using infrared video goggles and
      compared pair wise using Friedman tests. The perception of verticality was
      monitored using an ultrasound system for perceptual evaluation. The preliminary
      results of 4 cosmonauts showed a surprisingly large inter-individual variability
      of the measurements. Although OCR and perception of verticality appeared to be
      influenced overall by the exposure to microgravity, the wide variability among
      the cosmonauts obscured any statistical significance, in particular due to one
      cosmonauts being inconsistent with the other 3. Despite the specificity of the
      tests under normal conditions, the diverse response to spaceflight of our
      subjects exposes the complexity of the peripheral and central neural adaptive
      processes.

PMID- 23549053
TI  - The contribution of head position, standing surface and vision to postural
      control in young adults.
AB  - Postural control requires the integration of sensory information and is essential
      for performing every day movements and activities. Integrating sensory
      information from multiple sources may be challenging when competing sources of
      sensory information are affected. To further understand this complex
      relationship, this study investigated the contribution of varying sources of
      sensory information to postural control in healthy, young participants. Sixty
      young healthy adults (n=22 males; mean age, 24.6 +/- 2.1 SD years and (n=38
      females, mean age 24.0 +/- 1.4 SD years) were asked to maintain a stable posture
      under conditions that varied standing surface, head position and the availability
      of visual information. Sway velocity was largest when standing on foam with eyes
      closed and head extended (2.07 degrees /s) however, under the same visual-surface
      conditions with the head in a neutral position, sway velocity (1.59 degrees /s)
      was smaller yet remained significant. Findings from this study suggest that
      postural sway responses are dependent on the combined integration of available
      sources of sensory information. It is anticipated that such baseline information
      will allow us to apply our findings to the clinical management of individuals
      suffering from balance and vestibular impairments.

PMID- 23549054
TI  - Clinical interest of postural and vestibulo-ocular reflex changes induced by
      cervical muscles and skull vibration in compensated unilateral vestibular lesion
      patients.
AB  - Skull vibration induces nystagmus in unilateral vestibular lesion (UVL) patients.
      Vibration of skull, posterior cervical muscles or inferior limb muscles alters
      posture in recent UVL patients. This study aimed to investigate the postural
      effect of vibration in chronic compensated UVL patients. Vibration was applied
      successively to vertex, each mastoid, each side of posterior cervical muscles and
      of triceps surae in 12 UVL patients and 9 healthy subjects. Eye movements were
      recorded with videonystagmography. Postural control was evaluated in eyes open
      (EO) and eyes closed (EC) conditions. Sway area, sway path, anteroposterior and
      medio-lateral sways were recorded.A vibration induced nystagmus (VIN) beating
      toward the healthy side was obtained for each UVL patient during mastoid
      vibration. In EO, only sway path was higher in UVL group during vibration of
      mastoids and posterior cervical muscles.The EO postural impairments of UVL
      patients could be related to the eye movements or VIN, leading to visual
      perturbations, or to a proprioceptive error signal, providing an erroneous
      representation of head position. The vibration-induced sway was too small to be
      clinically useful. Vestibulo-ocular reflex observed with videonystagmography
      during mastoid vibration seems more relevant to reveal chronic UVL than vestibulo
      spinal reflex observed with posturography.

PMID- 23549055
TI  - Symptoms elicited in persons with vestibular dysfunction while performing gaze
      movements in optic flow environments.
AB  - INTRODUCTION: People with vestibular disorders often experience space and motion
      discomfort when exposed to moving or highly textured visual scenes. The purpose
      of this study was to measure the type and severity of symptoms in people with
      vestibular dysfunction during coordinated head and eye movements in optic flow
      environments. METHODS: Seven subjects with vestibular disorders and 25 controls
      viewed four different full-field optic flow environments on six different visits.
      The optic flow environments consisted of textures with various contrasts and
      spatial frequencies. Subjects performed 8 gaze movement tasks, including eye
      saccades, gaze saccades, and gaze stabilization tasks. Subjects reported symptoms
      using Subjective Units of Discomfort (SUD) and the Simulator Sickness
      Questionnaire (SSQ). Self-reported dizziness handicap and space and motion
      discomfort were also measured. RESULTS/CONCLUSION: Subjects with vestibular
      disorders had significantly greater discomfort, oculomotor and disorientation
      symptoms, with some amount of symptoms in 55-60% of the trials, compared with
      control subjects, who had symptoms in less than 20% of the trials. The magnitude
      of the symptoms increased during each visit, but did not depend on the optic flow
      condition. Subjects who reported greater dizziness handicap and space and motion
      discomfort had greater severity of symptoms during the experiment (Spearman rho >
      0.78). Compared with controls, subjects with vestibular disorders had about 10
      deg less head excursion during the gaze saccade tasks. Overall, performance of
      gaze pursuit and gaze stabilization tasks in moving visual environments elicited
      greater symptoms in subjects with vestibular disorders compared with healthy
      subjects.

PMID- 23549056
TI  - Use of pallidal deep brain stimulation in postinfarct hemidystonia.
AB  - BACKGROUND/AIMS: Reports of outcomes in treating dystonia secondary to stroke
      with deep brain stimulation (DBS) are limited. We report our experience with 3
      patients, all with infarcts involving the striatum, who developed hemidystonia
      and were treated with unilateral globus pallidus interna DBS. METHODS: Case
      series describing characteristics and outcomes based on the Burke-Fahn-Marsden
      Dystonia Rating Scale (BFMDRS) scores before and after DBS at 3, 6 and at least
      12 months. RESULTS: All patients reported subjective improvements after surgery.
      At 1 year or more after surgery, none of the 3 patients displayed a measureable
      improvement in the BFMDRS movement score. CONCLUSION: Our findings are consistent
      with previous reports of limited benefits from pallidal DBS in secondary
      dystonia. Future work should focus on predictive factors for DBS outcomes and the
      development of more sensitive assessment tools specifically for secondary
      dystonias as well as the exploration of alternative brain targets for
      stimulation.

PMID- 23549057
TI  - Evaluation of energy in heated water vapor for the application of lung volume
      reduction in patients with severe emphysema.
AB  - BACKGROUND: A method of achieving endoscopic lung volume reduction for emphysema
      has been developed that utilizes precise amounts of thermal energy in the form of
      water vapor to ablate lung tissue. OBJECTIVE: This study evaluates the energy
      output and implications of the commercial InterVapor system and compares it to
      the clinical trial system. METHODS: Two methods of evaluating the energy output
      of the vapor systems were used, a direct energy measurement and a quantification
      of resultant thermal profile in a lung model. Direct measurement of total energy
      and the component attributable to gas (vapor energy) was performed by condensing
      vapor in a water bath and measuring the temperature and mass changes. Infrared
      images of a lung model were taken after vapor delivery. The images were
      quantified to characterize the thermal profile. RESULTS: The total energy and
      vapor energy of the InterVapor system was measured at various dose levels and
      compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose
      of 8.5 cal/g was found to have the most similar vapor energy output with the
      smallest associated reduction in total energy. This was supported by
      characterization of the thermal profile in the lung model that demonstrated the
      profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical
      trial system. CONCLUSIONS: Considering both total energy and vapor energy is
      important during the development of clinical vapor applications. For InterVapor,
      a closer study of both energy types justified a reduced target vapor-dosing range
      for lung volume reduction. The clinical implication is a potential improvement
      for benefiting the risk profile.

PMID- 23549058
TI  - Foreign matter identification from solid dosage forms.
AB  - Despite the increased request for robust quality systems, the end product may
      contain unidentified defects or discoloured regions. The foreign matter has to be
      monitored, identified and its source defined in order to prevent further
      contamination. However, the identification task can be complicated, since the
      origin and nature of foreign matter are various. The aim of this study is to
      provide an efficient foreign matter identification procedure for various
      substances possibly originating from pharmaceutical manufacturing environment.
      The surface or cross-section of the uncoated and coated tablets was analysed by
      utilization of different analytical techniques, such as light microscopy (LM),
      scanning electron microscopy in combination with energy dispersive X-ray
      microanalysis (SEM/EDX), Fourier transform infrared spectroscopy (FT-IR) and time
      of-flight secondary ion mass spectrometry (ToF-SIMS). The results indicate that
      the combination of different analytical techniques proved to be a powerful
      approach in foreign matter identification. Light microscopy and SEM generate
      information on the morphology of foreign matter particles. EDX provides elemental
      analysis, which most often serves as final confirmation of the identification.
      However, FT-IR can be used to obtain information on the compounds chemical
      structure and conformation, and ToF-SIMS provides sensitivity in cases, where the
      entire solid dosage form is contaminated with foreign matter.

PMID- 23549059
TI  - Methodological considerations in longitudinal morphometry of traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) has recently been reconceptualized as a chronic,
      evolving disease process. This new view necessitates quantitative assessment of
      post-injury changes in brain structure that may allow more accurate monitoring
      and prediction of recovery. In particular, TBI is known to trigger
      neurodegenerative processes and therefore quantifying progression of diffuse
      atrophy over time is currently of utmost interest. However, there are various
      methodological issues inherent to longitudinal morphometry in TBI. In this paper,
      we first overview several of these methodological challenges: lesion evolution,
      neurosurgical procedures, power, bias, and non-linearity. We then introduce a
      sensitive, reliable, and unbiased longitudinal multivariate analysis protocol
      that combines dimensionality reduction and region of interest approaches. This
      analysis pipeline is demonstrated using a small dataset consisting of four
      chronic TBI survivors.

PMID- 23549060
TI  - Putative tumour suppressor gene necdin is hypermethylated and mutated in human
      cancer.
AB  - BACKGROUND: Necdin (NDN) expression is downregulated in telomerase-immortalised
      normal human urothelial cells. Telomerase-immortalised normal human urothelial
      cells have no detected genetic alterations. Accordingly, many of the genes whose
      expression is altered following immortalisation are those for which epigenetic
      silencing is reported. METHODS: NDN expression was examined in normal tissues and
      tumour cell lines by quantitative real-time PCR and immunoblotting.
      Immunohistochemistry was performed on urothelial carcinoma (UC). Urothelial
      carcinoma and UC cell lines were subject to HumanMethylation27 BeadChip Array
      based methylation analyses. Mutation screening was performed. The functional
      significance of NDN expression was investigated using retroviral-mediated
      downregulation or overexpression. RESULTS: NDN protein was widely expressed in
      normal tissues. Loss of expression was observed in 38 out of 44 (86%) of UC cell
      lines and 19 out of 25 (76%) of non-UC cell lines. Loss of NDN protein was found
      in the majority of primary UC. Oncomine analysis demonstrated downregulation of
      expression in multiple tumour types. In UC, tumour-specific hypermethylation of
      NDN and key CpG sites where hypermethylation correlated with reduced expression
      were identified. Six novel mutations, including some of predicted functional
      significance, were identified in colorectal and ovarian cancer cell lines.
      Functional studies showed that NDN could suppress colony formation at low cell
      density and affect anchorage-independent growth and anoikis in vitro. CONCLUSION:
      NDN is a novel tumour suppressor candidate that is downregulated and
      hypermethylated or mutated in cancer.

PMID- 23549061
TI  - New food allergies in a European non-Mediterranean region: is Cannabis sativa to
      blame?
AB  - BACKGROUND: Allergy to fruit and vegetables exhibit geographic variation
      regarding the severity of symptoms and depending on the sensitization profile of
      the patient. These sensitization profiles and routes remain incompletely
      understood. Cannabis is a very popular drug and derived from Cannabis sativa, a
      plant containing lipid transfer proteins (LTP) also known as important allergens
      in plant and fruit allergies. In this study we sought to elucidate a potential
      connection between C. sativa allergy and plant food allergies. METHODS: A case
      control study involving 21 patients consulting for plant food allergies. Twelve
      patients were cannabis allergic and 9 had a pollen or latex allergy without
      cannabis allergy. Testing for cannabis IgE implied measurement of specific IgE,
      skin testing and basophil activation tests. Allergen component analysis was
      performed with a microarray technique. RESULTS: Plant food allergy in patients
      with documented cannabis allergy had more severe reactions than patients without
      cannabis allergy and frequently implied fruits and vegetables that are not
      observed in a (birch) pollen-related food syndrome. With the exception of 1
      patient with cannabis allergy, all were sensitized to nonspecific (ns)-LTP.
      CONCLUSION: Our data suggest that illicit cannabis abuse can result in cannabis
      allergy with sensitization to ns-LTP. This sensitization might result in various
      plant-food allergies. Additional collaborative studies in different geographical
      areas are needed to further elucidate on this hypothesis.

PMID- 23549062
TI  - Structure reveals function of the dual variable domain immunoglobulin (DVD-IgTM)
      molecule.
AB  - Several bispecific antibody-based formats have been developed over the past 25
      years in an effort to produce a new generation of immunotherapeutics that target
      two or more disease mechanisms simultaneously. One such format, the dual-variable
      domain immunoglobulin (DVD-IgTM), combines the target binding domains of two
      monoclonal antibodies via flexible naturally occurring linkers, which yields a
      tetravalent IgG - like molecule. We report the structure of an interleukin (IL)12
      IL18 DVD-IgTM Fab (DFab) fragment with IL18 bound to the inner variable domain
      (VD) that reveals the remarkable flexibility of the DVD-IgTM molecule and how the
      DVD-IgTM format can function to bind four antigens simultaneously. An
      understanding of how the inner variable domain retains function is of critical
      importance for designing DVD-IgTM molecules, and for better understanding of the
      flexibility of immunoglobulin variable domains and linkers, which may aid in the
      design of improved bi- and multi-specific biologics in general. 

PMID- 23549063
TI  - Development of tube tetrodes and a multi-tetrode drive for deep structure
      electrophysiological recordings in the macaque brain.
AB  - Understanding the principles that underlie information processing by neuronal
      networks requires simultaneous recordings from large populations of well isolated
      single units. Twisted wire tetrodes (TWTs), typically made by winding together
      four ultrathin wires (diameter: 12-25 MUm), are ideally suited for such
      population recordings. They are advantageous over single electrodes; both with
      respect to quality of isolation as well as the number of single units isolated
      and have therefore been used extensively for superficial cortical recordings.
      However, their limited tensile strength poses a difficulty to their use for
      recordings in deep brain areas. We therefore developed a method to overcome this
      limitation and utilize tetrodes for electrophysiological recordings in the
      inferotemporal cortex of rhesus macaque. We fabricated a novel, stiff tetrode
      called the tube tetrode (TuTe) and developed a multi-tetrode driving system for
      advancing up to 5 TuTes through a ball and socket chamber to precise locations in
      the temporal lobe of a rhesus macaque. The signal quality acquired with TuTes was
      comparable to conventional TWTs and allowed excellent isolation of multiple
      single units. We describe here a simple method for constructing TuTes, which
      requires only standard laboratory equipment. Further, our TuTes can be easily
      adapted to work with other microdrives commonly used for electrophysiological
      investigation in the macaque brain and produce minimal damage to the cortex along
      its path because of their ultrathin diameter. The tetrode development described
      here could allow studying neuronal populations in deep lying brain structures
      previously difficult to reach with the current technology.

PMID- 23549064
TI  - The use of the diagnostic criteria for psychosomatic research in substance use
      disorder patients.

PMID- 23549065
TI  - A prognostic approach to defining chronic pain across a range of musculoskeletal
      pain sites.
AB  - OBJECTIVES: To test whether the prognostic definition of chronic pain, which has
      previously been applied in specific anatomic areas, performed well in a cohort of
      older adults with a range of musculoskeletal pain sites. METHODS: Data are taken
      from the Prognostic Research Study of adults aged 50 years and above consulting
      their general practitioner with any musculoskeletal pain, who completed postal
      surveys immediately after consultation and 12 months later. Baseline risk of
      clinically significant pain persisting at 12 months' follow-up, defined as a
      Chronic Pain Grade >=II, was calculated using the prognostic approach, which
      includes a range of pain and related factors. The approach was implemented using
      logistic regression models, and the performance of the approach, including
      cutoffs in the score to define groups with differing levels of risk, was assessed
      in terms of calibration and discrimination. RESULTS: Application of the original
      risk cutoffs created groups with increasing proportions of chronic pain (area
      under the curve =0.79). However, the probability of chronic pain in each group
      was higher than expected by the model. New cutoffs were defined for this group of
      older adults: score <=5=probability of chronic pain <20%, <=11=probability <50%,
      <=16=probability <80%, which resulted in good calibration of the model.
      DISCUSSION: The prognostic approach to defining chronic pain is suitable for use
      in older adults consulting primary care with musculoskeletal pain at a range of
      sites, but new cutoffs are needed to allow for the higher risk profile in this
      group. An adapted version of this method may also have the potential for
      application directly within the clinical consultation.

PMID- 23549066
TI  - Genome architecture and global gene regulation in bacteria: making progress
      towards a unified model?
AB  - Data obtained with advanced imaging techniques, chromosome conformation capture
      methods, bioinformatics and molecular genetics, together with insights from
      polymer physics and mechanobiology, are helping to refine our understanding of
      the spatiotemporal organization of the bacterial nucleoid and its gene expression
      programmes. Here, I discuss the proposal that, in addition to DNA topology and
      nucleoid-associated proteins, gene regulation is an important organizing
      principle of nucleoid architecture.

PMID- 23549067
TI  - Bacterial replication, transcription and translation: mechanistic insights from
      single-molecule biochemical studies.
AB  - Decades of research have resulted in a remarkably detailed understanding of the
      molecular mechanisms of bacterial DNA replication, transcription and translation.
      Our understanding of the kinetics and physical mechanisms that drive these
      processes forward has been expanded by the ability of single-molecule in vitro
      techniques, such as force spectroscopy and single-molecule Forster (fluorescence)
      resonance energy transfer (smFRET), to capture short-lived intermediate states in
      complex pathways. Furthermore, these technologies have revealed novel mechanisms
      that support enzyme processivity and govern the assembly of large multicomponent
      complexes. Here, we summarize the application of in vitro single-molecule studies
      to the analysis of fundamental bacterial processes, with a focus on the most
      recent functional insights that have been gained from fluorescence-based methods.

PMID- 23549077
TI  - CXCR7/CXCR4/CXCL12 axis regulates the proliferation, migration, survival and tube
      formation of choroid-retinal endothelial cells.
AB  - BACKGROUND/AIMS: Stromal cell-derived factor-1 (SDF-1) has been shown to mediate
      a broad range of biological processes via CXCR4, once regarded as its only
      receptor. CXCR7 is a recently identified receptor for SDF-1. This study aimed to
      investigate whether the CXCR7/CXCR4/SDF-1 axis is involved in choroidal
      neovascularization (CNV) formation in an in vitro hypoxic model. METHODS: CXCR7
      siRNA and/or CXCR4 siRNA was transfected into a hypoxic model of the choroid
      retinal endothelial RF/6A cell line. CCK-8 analysis, transwell migration
      analysis, annexin V-FITC and propidium iodide staining, and Matrigel tube
      formation analysis were performed to investigate the role of CXCR4 and CXCR7 in
      SDF-1-induced proliferation, migration, survival and tube formation of RF/6A
      cells. RESULTS: CXCR4, but not CXCR7, mediates SDF-1-induced RF/6A cell migration
      and proliferation under hypoxic conditions, whereas CXCR7 was exclusively
      involved in RF/6A cell survival. In addition, CXCR7 and CXCR4 acted together to
      regulate RF/6A cell tube formation. CONCLUSION: The CXCR7/CXCR4/SDF-1 axis plays
      an important role in the formation of CNV, and may become a novel target for the
      treatment of CNV-associated diseases.

PMID- 23549078
TI  - Applications of ambient mass spectrometry in high-throughput screening.
AB  - The development of rapid screening and identification techniques is of great
      importance for drug discovery, doping control, forensic identification, food
      safety and quality control. Ambient mass spectrometry (AMS) allows rapid and
      direct analysis of various samples in open air with little sample preparation.
      Recently, its applications in high-throughput screening have been in rapid
      progress. During the past decade, various ambient ionization techniques have been
      developed and applied in high-throughput screening. This review discusses typical
      applications of AMS, including DESI (desorption electrospray ionization), DART
      (direct analysis in real time), EESI (extractive electrospray ionization), etc.,
      in high-throughput screening (HTS).

PMID- 23549079
TI  - Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular
      development.
AB  - The identification of a gain-of-function mutation in CACNA1C as the cause of
      Timothy Syndrome (TS), a rare disorder characterized by cardiac arrhythmias and
      syndactyly, highlighted unexpected roles for the L-type voltage-gated Ca2+
      channel CaV1.2 in nonexcitable cells. How abnormal Ca2+ influx through CaV1.2
      underlies phenotypes such as the accompanying syndactyly or craniofacial
      abnormalities in the majority of affected individuals is not readily explained by
      established CaV1.2 roles. Here, we show that CaV1.2 is expressed in the first and
      second pharyngeal arches within the subset of cells that give rise to jaw
      primordia. Gain-of-function and loss-of-function studies in mouse, in concert
      with knockdown/rescue and pharmacological approaches in zebrafish, demonstrated
      that Ca2+ influx through CaV1.2 regulates jaw development. Cranial neural crest
      migration was unaffected by CaV1.2 knockdown, suggesting a role for CaV1.2 later
      in development. Focusing on the mandible, we observed that cellular hypertrophy
      and hyperplasia depended upon Ca2+ signals through CaV1.2, including those that
      activated the calcineurin signaling pathway. Together, these results provide new
      insights into the role of voltage-gated Ca2+ channels in nonexcitable cells
      during development.

PMID- 23549080
TI  - Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli
      ulcer formation.
AB  - Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium
      ulcerans, which induces the formation of open skin lesions referred to as Buruli
      ulcers. Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich
      syndrome protein (WASP) family of actin-nucleating factors. By disrupting WASP
      autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated
      assembly of actin in the cytoplasm. In epithelial cells, mycolactone-induced
      stimulation of ARP2/3 concentrated in the perinuclear region, resulting in
      defective cell adhesion and directional migration. In vivo injection of
      mycolactone into mouse ears consistently altered the junctional organization and
      stratification of keratinocytes, leading to epidermal thinning, followed by
      rupture. This degradation process was efficiently suppressed by coadministration
      of the N-WASP inhibitor wiskostatin. These results elucidate the molecular basis
      of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis.
      Our findings should allow for the rationale design of competitive inhibitors of
      mycolactone binding to N-WASP, with anti-Buruli ulcer therapeutic potential.

PMID- 23549081
TI  - Epitope specificity determines pathogenicity and detectability in ANCA-associated
      vasculitis.
AB  - Anti-neutrophil cytoplasmic antibody-associated (ANCA-associated) small vessel
      necrotizing vasculitis is caused by immune-mediated inflammation of the vessel
      wall and is diagnosed in some cases by the presence of myeloperoxidase-specific
      antibodies (MPO-ANCA). This multicenter study sought to determine whether
      differences in ANCA epitope specificity explain why, in some cases, conventional
      serologic assays do not correlate with disease activity, why naturally occurring
      anti-MPO autoantibodies can exist in disease-free individuals, and why ANCA are
      undetected in patients with ANCA-negative disease. Autoantibodies from human and
      murine samples were epitope mapped using a highly sensitive epitope excision/mass
      spectrometry approach. Data indicated that MPO autoantibodies from healthy
      individuals had epitope specificities different from those present in ANCA
      disease. Importantly, this methodology led to the discovery of MPO-ANCA in ANCA
      negative disease that reacted against a sole linear sequence. Autoantibodies
      against this epitope had pathogenic properties, as demonstrated by their capacity
      to activate neutrophils in vitro and to induce nephritis in mice. The confounder
      for serological detection of these autoantibodies was the presence of a fragment
      of ceruloplasmin in serum, which was eliminated in purified IgG, allowing
      detection. These findings implicate immunodominant epitopes in the pathology of
      ANCA-associated vasculitis and suggest that autoantibody diversity may be common
      to other autoimmune diseases.

PMID- 23549082
TI  - GSK-3alpha is a central regulator of age-related pathologies in mice.
AB  - Aging is regulated by conserved signaling pathways. The glycogen synthase kinase
      3 (GSK-3) family of serine/threonine kinases regulates several of these pathways,
      but the role of GSK-3 in aging is unknown. Herein, we demonstrate premature death
      and acceleration of age-related pathologies in the Gsk3a global KO mouse. KO mice
      developed cardiac hypertrophy and contractile dysfunction as well as sarcomere
      disruption and striking sarcopenia in cardiac and skeletal muscle, a classical
      finding in aging. We also observed severe vacuolar degeneration of myofibers and
      large tubular aggregates in skeletal muscle, consistent with impaired clearance
      of insoluble cellular debris. Other organ systems, including gut, liver, and the
      skeletal system, also demonstrated age-related pathologies. Mechanistically, we
      found marked activation of mTORC1 and associated suppression of autophagy markers
      in KO mice. Loss of GSK-3alpha, either by pharmacologic inhibition or Gsk3a gene
      deletion, suppressed autophagy in fibroblasts. mTOR inhibition rescued this
      effect and reversed the established pathologies in the striated muscle of the KO
      mouse. Thus, GSK-3alpha is a critical regulator of mTORC1, autophagy, and aging.
      In its absence, aging/senescence is accelerated in multiple tissues. Strategies
      to maintain GSK-3alpha activity and/or inhibit mTOR in the elderly could retard
      the appearance of age-related pathologies.

PMID- 23549083
TI  - Tumor fibroblast-derived epiregulin promotes growth of colitis-associated
      neoplasms through ERK.
AB  - Molecular mechanisms specific to colitis-associated cancers have been poorly
      characterized. Using comparative whole-genome expression profiling, we observed
      differential expression of epiregulin (EREG) in mouse models of colitis
      associated, but not sporadic, colorectal cancer. Similarly, EREG expression was
      significantly upregulated in cohorts of patients with colitis-associated cancer.
      Furthermore, tumor-associated fibroblasts were identified as a major source of
      EREG in colitis-associated neoplasms. Functional studies showed that Ereg
      deficient mice, although more prone to colitis, were strongly protected from
      colitis-associated tumors. Serial endoscopic studies revealed that EREG promoted
      tumor growth rather than initiation. Additionally, we demonstrated that
      fibroblast-derived EREG requires ERK activation to induce proliferation of
      intestinal epithelial cells (IEC) and tumor development in vivo. To demonstrate
      the functional relevance of EREG-producing tumor-associated fibroblasts, we
      developed a novel system for adoptive transfer of these cells via mini-endoscopic
      local injection. It was found that transfer of EREG-producing, but not Ereg
      deficient, fibroblasts from tumors significantly augmented growth of colitis
      associated neoplasms in vivo. In conclusion, our data indicate that EREG and
      tumor-associated fibroblasts play a crucial role in controlling tumor growth in
      colitis-associated neoplasms.

PMID- 23549084
TI  - Hepatic glucose sensing is required to preserve beta cell glucose competence.
AB  - Liver glucose metabolism plays a central role in glucose homeostasis and may also
      regulate feeding and energy expenditure. Here we assessed the impact of glucose
      transporter 2 (Glut2) gene inactivation in adult mouse liver (LG2KO mice). Loss
      of Glut2 suppressed hepatic glucose uptake but not glucose output. In the fasted
      state, expression of carbohydrate-responsive element-binding protein (ChREBP) and
      its glycolytic and lipogenic target genes was abnormally elevated. Feeding,
      energy expenditure, and insulin sensitivity were identical in LG2KO and control
      mice. Glucose tolerance was initially normal after Glut2 inactivation, but LG2KO
      mice exhibited progressive impairment of glucose-stimulated insulin secretion
      even though beta cell mass and insulin content remained normal. Liver transcript
      profiling revealed a coordinated downregulation of cholesterol biosynthesis genes
      in LG2KO mice that was associated with reduced hepatic cholesterol in fasted mice
      and reduced bile acids (BAs) in feces, with a similar trend in plasma. We showed
      that chronic BAs or farnesoid X receptor (FXR) agonist treatment of primary
      islets increases glucose-stimulated insulin secretion, an effect not seen in
      islets from Fxr(-/-) mice. Collectively, our data show that glucose sensing by
      the liver controls beta cell glucose competence and suggest BAs as a potential
      mechanistic link.

PMID- 23549085
TI  - Myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency
      reduces murine atherosclerosis.
AB  - Serine palmitoyltransferase (SPT) is the first and rate-limiting enzyme of the de
      novo biosynthetic pathway of sphingomyelin (SM). Both SPT and SM have been
      implicated in the pathogenesis of atherosclerosis, the development of which is
      driven by macrophages; however, the role of SPT in macrophage-mediated
      atherogenesis is unknown. To address this issue, we have analyzed macrophage
      inflammatory responses and reverse cholesterol transport, 2 key mediators of
      atherogenesis, in SPT subunit 2-haploinsufficient (Sptlc2(+/-)) macrophages. We
      found that Sptlc2(+/-) macrophages have significantly lower SM levels in plasma
      membrane and lipid rafts. This reduction not only impaired inflammatory responses
      triggered by TLR4 and its downstream NF-kappaB and MAPK pathways, but also
      enhanced reverse cholesterol transport mediated by ABC transporters. LDL receptor
      deficient (Ldlr(-/-)) mice transplanted with Sptlc2(+/-) bone marrow cells
      exhibited significantly fewer atherosclerotic lesions after high-fat and high
      cholesterol diet feeding. Additionally, Ldlr(-/-) mice with myeloid cell-specific
      Sptlc2 haploinsufficiency exhibited significantly less atherosclerosis than
      controls. These findings suggest that SPT could be a novel therapeutic target in
      atherosclerosis.

PMID- 23549086
TI  - Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells.
AB  - IL-11 and its receptor, IL-11Ra, are expressed in human cancers; however, the
      functional role of IL-11 in tumor progression is not known. We found that IL11 is
      a hypoxia-inducible, VHL-regulated gene in human cancer cells and that expression
      of IL11 mRNA was dependent, at least in part, on HIF-1. A cooperative interaction
      between HIF-1 and AP-1 mediated transcriptional activation of the IL11 promoter.
      Additionally, we found that human cancer cells expressed a functional IL-11Ra
      subunit, which triggered signal transduction either by exogenous recombinant
      human IL-11 or by autocrine production of IL-11 in cells cultured under hypoxic
      conditions. Silencing of IL11 dramatically abrogated the ability of hypoxia to
      increase anchorage-independent growth and significantly reduced tumor growth in
      xenograft models. Notably, these results were phenocopied by partial knockdown of
      STAT1 in a human prostate cancer cell line (PC3), suggesting that this pathway
      may play an important role in mediating the effects of IL-11 under hypoxic
      conditions. In conclusion, these results identify IL11 as an oxygen- and VHL
      regulated gene and provide evidence of a pathway "hijacked" by hypoxic cancer
      cells that may contribute to tumor progression.

PMID- 23549088
TI  - You are who you talk with--a commentary on Dugas-Ford et al. PNAS, 2012.

PMID- 23549089
TI  - Cucurbit[7]uril as a "protective agent": controlling photochemistry and detecting
      1-adamantanamine.
AB  - Cucurbit[7]uril (CB[7]) as a "protective agent" can effectively inhibit the [4+4]
      photochemical reaction of 1,1'-(butane-1,4-diyl)bis(2-aminopyridine)bromide
      (DPAD) by host-guest interaction between CB[7] and DPAD. In addition, the host
      guest complex DPAD-CB[7] as a supramolecular sensor can detect the concentration
      of 1-adamantanamine with good sensitivity and selectivity because of the guest
      competitive complexation.

PMID- 23549087
TI  - Eliminating malignant contamination from therapeutic human spermatogonial stem
      cells.
AB  - Spermatogonial stem cell (SSC) transplantation has been shown to restore
      fertility in several species and may have application for treating some cases of
      male infertility (e.g., secondary to gonadotoxic therapy for cancer). To ensure
      safety of this fertility preservation strategy, methods are needed to isolate and
      enrich SSCs from human testis cell suspensions and also remove malignant
      contamination. We used flow cytometry to characterize cell surface antigen
      expression on human testicular cells and leukemic cells (MOLT-4 and TF-1a). We
      demonstrated via FACS that EpCAM is expressed by human spermatogonia but not MOLT
      4 cells. In contrast, HLA-ABC and CD49e marked >95% of MOLT-4 cells but were not
      expressed on human spermatogonia. A multiparameter sort of MOLT-4-contaminated
      human testicular cell suspensions was performed to isolate EpCAM+/HLA-ABC-/CD49e-
      (putative spermatogonia) and EpCAM-/HLA-ABC+/CD49e+ (putative MOLT-4) cell
      fractions. The EpCAM+/HLA-ABC-/CD49e- fraction was enriched for spermatogonial
      colonizing activity and did not form tumors following human-to-nude mouse
      xenotransplantation. The EpCAM-/HLA-ABC+/CD49e+ fraction produced tumors
      following xenotransplantation. This approach could be generalized with slight
      modification to also remove contaminating TF-1a leukemia cells. Thus, FACS
      provides a method to isolate and enrich human spermatogonia and remove malignant
      contamination by exploiting differences in cell surface antigen expression.

PMID- 23549090
TI  - Intrauterine hormone effects on tooth dimensions.
AB  - The human dentition is a complex adaptive system that is influenced by genetic,
      epigenetic, and environmental factors. Within this system, is sexual dimorphism
      related to the growth promotion of the Y chromosome, or to hormonal influences,
      or both? This study is the first to investigate both primary and permanent tooth
      sizes in females from opposite-sex dizygotic (DZOS) twin pairs compared with
      females from dizygotic same-sex (DZSS) and monozygotic (MZ) twin pairs to
      indicate the influence of intrauterine male hormone, including the initial
      testosterone surge, on dental development. Serial dental models of the primary,
      mixed, and permanent dentitions of 134 females from DZOS, DZSS, and MZ twins were
      examined. Mesiodistal, buccolingual, crown height, and intercuspal dimensions of
      all primary teeth and selected permanent teeth were determined by image analysis.
      Univariate and multivariate analyses showed statistically significantly larger
      crown size in DZOS females in both dentitions, with the crown height dimensions
      displaying the greatest increase in size. These findings strongly support the
      Twin Testosterone Transfer (TTT) hypothesis. We propose that the growth-promoting
      effects of the Y chromosome and intrauterine male hormone levels influence
      different tooth dimensions and contribute differentially to the sexual dimorphism
      of human teeth.

PMID- 23549091
TI  - Theoretical foundations and clinical implications of formal psychological
      assessment.

PMID- 23549092
TI  - Genetic and environmental factors associated with reticular pseudodrusen in age
      related macular degeneration.
AB  - PURPOSE: To analyze the genetic and environmental factors associated with
      reticular pseudodrusen (RPD) in age-related macular degeneration (AMD). METHODS:
      In a large population, AMD patients (n = 519) with and without RPD were assessed
      with a standardized examination including infrared images and spectral domain
      optical coherence tomography scans. Three groups were defined: Group 1: AMD
      patients with RPD (n = 105); Group 2: AMD patients without RPD (n = 414); and
      Group 3: controls with no AMD and no RPD (n = 430). Four genes associated with
      AMD (CFH, ARMS2/HTRA1, C3, apolipoprotein E) and environmental factors were
      assessed between the 3 groups. RESULTS: None of the environmental factors studied
      were more significantly associated to either Group 1 or Group 2. The odds ratios
      and 95% confidence intervals for individuals homozygous for the CFH risk allele
      were 4.0 (2.1-7.7) ([95% confidence interval: 2.1-7.7]; P < 0.0004) in Group 1
      and 4.3 ([2.6-7.1]; P < 0.0004) in Group 2, compared with Group 3. The odds
      ratios for individuals homozygous for the ARMS2 risk allele for Groups 1 and 2
      compared with Group 3 were 16.3 ([7.6-35.4]; P < 0.0004) and 11.9 ([6.3-22.3]; P
      < 0.0004), respectively. None of the genotypes studied were more significantly
      associated to Group 1 than Group 2. CONCLUSION: Genotypes known to be associated
      with AMD were similarly observed in patients with and without RPD.

PMID- 23549093
TI  - Reply: To PMID 22791178.

PMID- 23549094
TI  - "Sutureless silicone oil removal: a quick and safe technique".

PMID- 23549095
TI  - Reply: To PMID 22277906.

PMID- 23549096
TI  - Ultra-widefield autofluorescence imaging in the evaluation of scleral buckling
      surgery for retinal detachment.
AB  - PURPOSE: To investigate the use of ultra-widefield fundus autofluorescence
      imaging in the early postoperative evaluation of scleral buckling surgery for
      retinal detachment. METHODS: Forty-five eyes from 44 patients with rhegmatogenous
      retinal detachment were included. Ultra-widefield fundus autofluorescence imaging
      (Optomap P200Tx) was performed from both eyes preoperatively and early (1-2 days)
      postoperatively. All patients were operated with 2.5-mm encircling band, 6-mm to
      9-mm segmental buckle, transscleral cryopexy, and the choice of drainage and
      air/gas endotamponade. RESULTS: The mean age of the patients was 58 +/- 12 years,
      and the ratio of macula on-off detachments was 19/26. Light cryopexy induced
      hyperfluorescence of the treated area (in 11% of cases). Moderate cryopexy
      resulted in central hypofluorescence with a hyperfluorescent halo (in 51% of
      cases), whereas extensive cryopexy and disruption of the retinal pigment
      epithelium resulted in a broad hypofluorescent area (in 36% of cases). Tightening
      of the indenting elements induced peripheral hyperfluorescent radial streaks in
      47% of cases and distinct areas of hyperfluorescence in 58% of cases. Demarcation
      lines and residual subretinal fluid were observed as hyperfluorescent areas.
      Central autofluorescence changes were observed in 96% of macula-off surgeries,
      whereas only 27% of these cases showed distinct hyper- and hypo-autofluorescent
      streaks. CONCLUSION: Ultra-widefield fundus autofluorescence imaging is a useful
      adjuvant tool for evaluating early outcome and retinal pigment epithelium
      function after scleral buckling surgery for retinal detachment.

PMID- 23549097
TI  - Postoperative outcomes after fluocinolone acetonide implant surgery in patients
      with birdshot chorioretinitis and other types of posterior and panuveitis.
AB  - PURPOSES: To evaluate outcomes after placement of fluocinolone acetonide (FA)
      implants in eyes with birdshot chorioretinitis and to compare these outcomes with
      eyes with posterior and panuveitis. METHODS: This is a retrospective cohort study
      of 48 eyes from patients with posterior and panuveitis treated with FA implants
      from 2006 to 2010. Outcome measures include visual acuity, intraocular pressure,
      need for glaucoma surgery, postoperative complications, and control of
      inflammation. RESULTS: All eyes treated with FA implants achieved improved
      control of inflammation and decreased reliance on adjunctive therapy. Birdshot
      chorioretinitis eyes had a statistically significant increase in intraocular
      pressure in the first 4 months after FA implantation (P = 0.04) compared with
      baseline intraocular pressure. A higher percentage of eyes with birdshot
      chorioretinitis required glaucoma surgery and after a shorter time period after
      FA implantation than did eyes with other forms of posterior and panuveitis
      (0.42/eye-year vs. 0.11/eye-year; median time to glaucoma surgery: 15.5 months
      vs. 31.5 months respectively, hazard ratio, 3.4; 95% confidence interval, 1.0
      10.8, P = 0.04). CONCLUSION: Although the FA implant is effective in controlling
      inflammation and reducing the need for systemic immunosuppressive therapy, eyes
      of patients with birdshot chorioretinitis tend to have a more robust intraocular
      pressure response to the FA implant than eyes with other types of posterior and
      panuveitis.

PMID- 23549098
TI  - "Vitrectomy without face-down posturing for idiopathic macular holes".

PMID- 23549099
TI  - Reply: To PMID 22080914.

PMID- 23549100
TI  - LuceDex: a prospective study comparing ranibizumab plus dexamethasone combination
      therapy versus ranibizumab monotherapy for neovascular age-related macular
      degeneration.
AB  - BACKGROUND: The LuceDex prospective randomized pilot trial compared the
      combination of intravitreal ranibizumab and dexamethasone with ranibizumab
      monotherapy for treatment of neovascular age-related macular degeneration.
      METHODS: Thirty-seven eyes of 37 patients were randomized 1:1 between combination
      therapy with intravitreal ranibizumab and dexamethasone (Group 1) and
      intravitreal ranibizumab monotherapy (Group 2). All study eyes received 4 monthly
      treatments followed by monthly treatment on indication. RESULTS: In the LuceDex
      study, eyes gained an average of 11.1 and 5.9 Early Treatment of Diabetic
      Retinopathy Study letters in Groups 1 and 2, respectively, at Month 12. No more
      than zero Early Treatment of Diabetic Retinopathy Study letters were lost in 88%
      of Group 1 eyes and 70% of Group 2 eyes. The average number of treatments per
      study eye by Month 12 was 7.1 in Group 1 and 6.6 in Group 2. Choroidal
      neovascular membrane size decreased in Group 1 significantly compared with Group
      2 (P < 0.05). CONCLUSION: The LuceDex pilot study suggested a possible benefit of
      adding intravitreal dexamethasone to treatment of neovascular age-related macular
      degeneration with intravitreal ranibizumab. A larger study is needed to further
      identify and define possible benefits of this combination therapy.

PMID- 23549101
TI  - Visual and anatomical outcomes of intravitreal aflibercept in eyes with
      persistent subfoveal fluid despite previous treatments with ranibizumab in
      patients with neovascular age-related macular degeneration.
AB  - PURPOSE: To assess the efficacy of intravitreal aflibercept (2.0 mg) in patients
      with treatment-resistant neovascular age-related macular degeneration. METHODS:
      Retrospective analysis of eyes treated with aflibercept with persistent
      subretinal and/or intraretinal fluid despite previous treatments with
      intravitreal ranibizumab (0.5 mg). All patients were switched to intravitreal
      aflibercept (2.0 mg) and analyzed after 3 consecutive injections and after 6
      months of treatment. Main outcome measures included change in visual acuity,
      central foveal thickness, and the height and diameter of the pigment epithelial
      detachment on the subfoveal scan on optical coherence tomography. RESULTS: Thirty
      four eyes of 33 patients were analyzed. Mean duration of symptoms and average
      number of previous injections with anti-vascular endothelial growth factor agents
      was 44.7 +/- 29.8 months (interquartile range [IQR] 24-76 months) and 28.6 +/-
      20.1 (IQR 10-47), respectively. At the 6-month follow-up, mean visual acuity and
      central foveal thickness improved significantly from 20/75 (logarithm of minimum
      angle of resolution 0.57 +/- 0.36; IQR 0.30-1.0) and 416 +/- 217 MUm (IQR 263-487
      MUm) at baseline to 20/60 (logarithm of minimum angle of resolution 0.47 +/-
      0.32; IQR 0.30-0.60) (P = 0.004) and 248 +/- 171 MUm (IQR 235-419 MUm) (P <
      0.001), respectively. Maximum pigment epithelial detachment height improved
      significantly from 260 +/- 162 MUm (IQR 129-368 MUm) to 214 +/- 142 MUm (IQR 111
      305 MUm) (P < 0.001) and PED diameter decreased significantly from 3,265 +/-
      1,622 MUm (IQR 2,353-4,555 MUm) to 2,949 +/- 1,653 MUm (IQR 1,721-4,484 MUm) (P =
      0.04). CONCLUSION: Intravitreal injections of aflibercept resulted in a
      significant improvement in visual and anatomical outcomes in eyes with persistent
      subfoveal fluid despite previous treatment with ranibizumab.

PMID- 23549102
TI  - Circulating miRNA profile in HCV infected serum: novel insight into pathogenesis.
AB  - Changes in circulating miRNA profiles have been associated with different
      diseases. Here we demonstrate the circulating miRNA profile in serum of HCV
      infected individuals using a microRNA array that profiles the expression of 940
      miRNAs. Serum samples from two HCV genotype - 1 and two HCV genotype - 3 infected
      individuals were compared with healthy controls. Expression levels of miR-134,
      miR-198, miR-320c and miR-483-5p that were commonly upregulated in case of both
      genotypes were validated in 36 individual patient serum samples. Serum miR-134,
      miR-320c and miR-483-5p were significantly upregulated during HCV infection. miR
      320c and miR-483-5p were also upregulated in HCV- JFH1 infected cells and cell
      culture supernatant. Pathway analysis of putative target genes of these miRNAs
      indicated involvement of PI3K-Akt, NFKB and MAPK signaling pathways. Results
      revealed novel insights on the role of circulating miRNAs in mediating
      pathogenesis in HCV-infected cells.

PMID- 23549104
TI  - Comparison of voice quality after laser cordectomy with that after radiotherapy
      or chemoradiotherapy for early glottic carcinoma.
AB  - PURPOSE OF THE STUDY: The present study aimed to compare the voice quality after
      each type of cordectomy with that after radiotherapy (RT) or chemoradiotherapy
      (CRT) for early glottic carcinoma. PROCEDURES: The GRBAS perceptive scale
      [consisting of 5 domains: grade (G), roughness (R), breathiness (B), asthenia
      (A), and strain (S)], aerodynamic tests and acoustic analyses, and the Voice
      Handicap Index questionnaire were evaluated for 58 laser cordectomy cases and 40
      RT or CRT cases. Multiple comparison tests were conducted between each type of
      cordectomy and RT or CRT. RESULTS: No statistical difference was found between
      type I/II cordectomy and RT for T1 glottic carcinoma (T1RT), whereas T1RT showed
      a significantly better outcome than type III cordectomy (G score: p = 0.016,
      maximum phonation time: p < 0.01, mean flow rate: p < 0.01). Type IV cordectomy
      was equivalent to RT or CRT for T2 glottic carcinoma (T2RT/CRT), while types V
      and VI showed a worse voice quality than T2RT/CRT (G score: p = 0.038 to type VI,
      B score: p = 0.025 to type V and p = 0.032 to type VI, A score: p = 0.017 to type
      VI). CONCLUSIONS: Voice quality after laser cordectomy differs according to the
      type of cordectomy. Surgeons should inform patients about the expected voice
      quality after each treatment modality.

PMID- 23549103
TI  - Immune suppression in cynomolgus monkeys by XPro9523: an improved CTLA4-Ig fusion
      with enhanced binding to CD80, CD86 and neonatal Fc receptor FcRn.
AB  - The CTLA4-Ig fusion proteins abatacept and belatacept are clinically proven
      immunosuppressants used for rheumatoid arthritis and renal transplant,
      respectively. Given that both biologics are typically administered chronically by
      infusion, a need exists for a next-generation CTLA4-Ig with more convenient
      dosing. We used structure-based protein engineering to optimize the affinity of
      existing CTLA4-Ig therapeutics for the ligands CD80 and CD86, and for the
      neonatal Fc receptor, FcRn. From a rationally designed library, we identified
      four substitutions that enhanced binding to human CD80 and CD86. Coupled with two
      IgG1 Fc substitutions that enhanced binding to human FcRn, these changes comprise
      the novel CTLA4-Ig fusion protein, XPro9523. Compared with abatacept, XPro9523
      demonstrated 5.9-fold, 23-fold, and 12-fold increased binding to CD80, CD86, and
      FcRn, respectively; compared with belatacept, CD80, CD86, and FcRn binding
      increased 1.5-fold, 7.7-fold, and 11-fold, respectively. XPro9523 and belatacept
      suppressed human T cell proliferation and IL-2 production more potently than
      abatacept. XPro9523 also suppressed inflammation in the mouse collagen-induced
      arthritis model. In cynomolgus monkeys, XPro9523 saturated CD80 and CD86 more
      effectively than abatacept and belatacept, potently inhibited IgM and IgG
      immunization responses, and demonstrated longer half-life. Pharmacokinetic
      modeling of its increased potency and persistence suggests that, in humans,
      XPro9523 may demonstrate superior efficacy and dosing convenience compared with
      abatacept and belatacept. 

PMID- 23549106
TI  - A never-ending search for the evolutionary origin of the neocortex: rethinking
      the homology concept.

PMID- 23549107
TI  - In the spotlight: Biomedical imaging.

PMID- 23549108
TI  - The role of technology and engineering models in transforming healthcare.
AB  - The healthcare system is in crisis due to challenges including escalating costs,
      the inconsistent provision of care, an aging population, and high burden of
      chronic disease related to health behaviors. Mitigating this crisis will require
      a major transformation of healthcare to be proactive, preventive, patient
      centered, and evidence-based with a focus on improving quality-of-life.
      Information technology, networking, and biomedical engineering are likely to be
      essential in making this transformation possible with the help of advances, such
      as sensor technology, mobile computing, machine learning, etc. This paper has
      three themes: 1) motivation for a transformation of healthcare; 2) description of
      how information technology and engineering can support this transformation with
      the help of computational models; and 3) a technical overview of several research
      areas that illustrate the need for mathematical modeling approaches, ranging from
      sparse sampling to behavioral phenotyping and early detection. A key tenet of
      this paper concerns complementing prior work on patient-specific modeling and
      simulation by modeling neuropsychological, behavioral, and social phenomena. The
      resulting models, in combination with frequent or continuous measurements, are
      likely to be key components of health interventions to enhance health and
      wellbeing and the provision of healthcare.

PMID- 23549109
TI  - Surgical outcomes of microsurgical selective peripheral neurotomy for intractable
      limb spasticity.
AB  - BACKGROUND: The authors frequently employed selective peripheral neurotomy (SPN)
      as the primary treatment of severe intractable focal and multifocal spastic
      hypertonia. We occasionally operated SPN in diffuse spastic disorders. OBJECTIVE:
      To study surgical outcome of SPN in terms of severity of spasticity and
      functional condition. METHODS: Patients harboring refractory harmful spasticity
      of various origins were enrolled into the present study. They were clinically
      evaluated by using the Modified Ashworth Scale (MAS), passive range of motion
      (PROM) and functional status. These variables were compared between pre- and
      postsurgery by using the paired t test and the Wilcoxon signed-rank matched-pairs
      test. RESULTS: One hundred and forty-one SPNs were accomplished in 33 patients.
      Overall mean pre- and postoperative MAS and PROM were 3.0 and 0.7 (p < 0.001) and
      78.3 and 102.3 degrees  (p < 0.001), respectively. Analysis of individual SPN
      subgroups also demonstrated statistically significant improvement of both
      parameters. Furthermore, we found significant gait improvement among 10
      ambulatory subjects. Nine bed-bound cases attained significant enhancement of
      sitting competency and ambulatory condition. CONCLUSION: SPN is an efficacious
      neurosurgical intervention in the treatment of spasticity. It is apparently
      beneficial in the reduction of spasticity, amelioration of functional status,
      facilitation of patient care and prevention of long-term musculoskeletal
      sequelae.

PMID- 23549110
TI  - Therapist perceptions and delivery of interoceptive exposure for panic disorder.
AB  - Interoceptive exposure (IE) is widely regarded as an essential procedure in the
      cognitive-behavioral treatment of panic disorder (PD). However, treatment manuals
      differ substantially in their prescribed delivery of IE, and little research
      exists to inform the optimal manner of its implementation. The present study
      examined therapists' perceptions and delivery of IE for PD. Results revealed
      substantial variability in how clinicians provide IE. In contrast to the
      prolonged and intense manner in which exposure techniques are traditionally
      applied, many therapists reported delivering a low dose of IE accompanied by
      controlled breathing strategies. Concerns about the potential adverse effects of
      IE were common despite the fact that participants reported the actual occurrence
      of negative outcomes of IE in their own practice to be extremely infrequent. It
      is possible that some therapists deliver IE in a cautious manner in an attempt to
      minimize the perceived risks associated with this treatment.

PMID- 23549111
TI  - Rovibrational states of ClHCl- isotopologues up to high J: a joint theoretical
      and spectroscopic investigation.
AB  - Explicitly correlated coupled cluster theory at the CCSD(T*)-F12b level (T. B.
      Adler, G. Knizia, and H.-J. Werner, J. Chem. Phys., 2007, 127, 221106) and two
      precise spectroscopic parameters (K. Kawaguchi, J. Chem. Phys., 1988, 88, 4186)
      were used to construct an accurate near-equilibrium analytical potential energy
      function (PEF) for the highly anharmonic centrosymmetric hydrogen-bonded complex
      ClHCl(-) (Re = 3.1153 A). From variational calculations with that PEF, a large
      number of rovibrational energies of different isotopologues up to high values of
      the rotational quantum number J was obtained. Theory helped with the assignment
      of lines observed by IR diode laser spectroscopy in the nu1 + nu3 combination
      band of (35)ClH(35)Cl(-) and (37)ClH(35)Cl(-) and enabled us to elucidate rather
      subtle patterns of rovibrational interactions. Furthermore, transition dipole
      moments were predicted and analysed as well as unusual isotopic effects.

PMID- 23549112
TI  - A ferromagnetically coupled diphenoxo-bridged Gd(3+)-Mn2+ dinuclear complex with
      a large magneto-caloric effect.
AB  - A novel diphenoxo-bridged Gd(3+)-Mn(2+) dimer is proposed as a good candidate for
      cryogenic magnetic refrigeration. The large MCE is enhanced by the ferromagnetic
      interaction between the two metal ions.

PMID- 23549113
TI  - Radical induced disulfide bond cleavage within peptides via ultraviolet
      irradiation of an electrospray plume.
AB  - Radical induced disulfide bond cleavage in peptides was demonstrated by
      ultraviolet (UV) radiation of the electrospray ionization (ESI) plume using a low
      pressure mercury (LP-Hg) lamp. Tandem mass spectrometry and accurate mass
      measurements confirmed that the primary reaction products were due to disulfide
      bond cleavage to form thiol (-SH) and sulfinyl radical (-SO). Mechanistic studies
      showed that the 185 nm emission from a LP-Hg lamp was responsible for UV
      photolysis of atmospheric O2, which further initiated secondary radical formation
      and subsequent disulfide bond cleavage by radical attack. The radical induced
      disulfide bond cleavage was found to be analytically useful in providing rich
      sequence information for naturally occurring peptides containing intrachain
      disulfide bonds. The utility of this method was also demonstrated for facile
      disulfide peptide identification and characterization from protein digests.

PMID- 23549118
TI  - The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells.
AB  - The genes POU5F1 and SOX2 are critical for pluripotency and reprogramming, yet
      the chromosomal organization around these genes remains poorly understood. We
      assayed long-range chromosomal interactions on putative enhancers of POU5F1 and
      SOX2 genes in human embryonic stem cells (hESCs) using 4C-Seq technique. We
      discovered that their frequent interacting regions mainly overlap with early DNA
      replication domains. The interactomes are associated with active histone marks
      and enriched with 5-hydroxymethylcytosine sites. In hESCs, genes within the
      interactomes have elevated expression. Additionally, some genes associated with
      the POU5F1 enhancer contribute to pluripotency. Binding sites for multiple DNA
      binding proteins, including ATF3, CTCF, GABPA, JUND, NANOG, RAD21 and YY1, are
      enriched in both interactomes. The RARG locus, frequently interacting with the
      POU5F1 locus, has abundant RAD21 binding sites co-localized with other protein
      binding sites. Thus the interactomes of these two pluripotency genes could be an
      important part of the regulatory network in hESCs.

PMID- 23549119
TI  - Low-dose droperidol for prevention of postoperative nausea in adults.

PMID- 23549120
TI  - Ventilation with a view and usefulness of Airtraq laryngoscope: the response to
      an observational study.

PMID- 23549121
TI  - Impact of depth of hypnosis on immediate postoperative cognitive function: A
      randomised trial.

PMID- 23549122
TI  - The effect of transversus abdominis plane block or local anaesthetic infiltration
      in inguinal hernia repair: a randomised clinical trial.
AB  - CONTEXT: The analgesic effect of transversus abdominis plane (TAP) block after
      inguinal hernia repair is unclear. OBJECTIVE: The aim of this randomised and
      double-blind study was to evaluate the analgesic effect of a TAP block in
      patients scheduled for primary inguinal hernia repair. The TAP block was
      evaluated versus placebo and versus an active comparator (ilioinguinal block and
      wound infiltration). DESIGN: Randomised controlled trial. SETTING: Single centre
      trial. Study period from June 2010 to November 2011. PATIENTS: Adults (18 to 75
      years) with American Society of Anesthesiologists' status 1-3 scheduled for
      primary inguinal hernia repair as day case surgery were included in the study.
      INTERVENTIONS: Ninety patients were allocated to one of three groups: group TAP,
      group infiltration (ilioinguinal nerve block and wound infiltration) and group
      placebo. MAIN OUTCOME MEASURES: The primary outcome measure was pain scores while
      coughing between group TAP and group placebo calculated as area under the curve
      for the first 24  h (AUC24 h). Secondary outcomes were pain scores while coughing
      and at rest, opioid consumption and side effects in groups TAP, infiltration and
      placebo. RESULTS: Visual analogue pain scores while coughing and at rest
      demonstrated no difference between groups. Pain scores in groups infiltration,
      TAP and placebo were 19 versus 22 versus 15  mm at rest (P = 1.00) and 37 versus
      41 versus 37  mm while coughing (P = 1.00). Pain scores at 6 h (AUC6 h) were
      significantly lower in group infiltration than in group TAP (10 versus 25 mm at
      rest, P < 0.001; 17 versus 40  mm while coughing, P < 0.001), and than in group
      placebo (10 versus 20  mm at rest, P = 0.003; 17 versus 38  mm while coughing, P
      < 0.001). Median morphine consumption was lower in group infiltration than in
      group placebo (0 versus 5 mg, P < 0.003). No differences among groups were
      demonstrated for ketobemidone consumption or side effects. CONCLUSION: Ultrasound
      guided TAP block did not reduce postoperative pain after inguinal hernia repair.
      TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01052285. EudraCT number
      2010-018403-29.

PMID- 23549123
TI  - Analgesic efficacy of ultrasound-guided adductor canal blockade after
      arthroscopic anterior cruciate ligament reconstruction: a randomised controlled
      trial.
AB  - CONTEXT: Anterior cruciate ligament (ACL) reconstruction surgery is associated
      with moderate to severe postoperative pain, which may be ameliorated by
      peripheral nerve blocks. The adductor canal block (ACB) is an almost exclusively
      sensory nerve block that has been demonstrated to reduce pain and opioid
      consumption after major knee surgery. OBJECTIVES: To investigate the analgesic
      effect of ACB in patients receiving a basic analgesic regimen of paracetamol and
      ibuprofen after arthroscopic ACL reconstruction under general anaesthesia.
      DESIGN: Randomised, double-blind, placebo-controlled, parallel groups. SETTING:
      Day Case Surgery, University of Copenhagen, Glostrup Hospital, Denmark, June 2010
      to March 2012. PATIENTS: Fifty patients, aged 18 to 70 years, scheduled for
      arthroscopic ACL reconstruction. INTERVENTIONS: Patients were randomised to
      receive ACB with either 30  ml ropivacaine 7.5  mg ml (n = 25) or 30  ml 0.9%
      saline (n = 24). MAIN OUTCOME MEASURES: Primary outcome was pain score (0 to 100 
      mm) during standing at 2  h after surgery. Secondary outcomes were pain at rest,
      during standing and after walking 5 m, opioid consumption and opioid-related side
      effects for 24  h after surgery. RESULTS: Median (interquartile range) pain
      scores for the primary outcome were 20 (12 to 36)  mm in the ropivacaine and 20
      (10 to 44) mm in the control group (P = 0.84, 95% confidence interval for
      difference of -9 to 12 mm). No significant differences were observed in any of
      the secondary outcomes. CONCLUSION: An analgesic regimen with paracetamol and
      ibuprofen provides acceptable postoperative pain control after arthroscopic ACL
      reconstruction. ACB did not confer further benefit in our patients. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier: NCT01212666.

PMID- 23549124
TI  - Reply to: Optimal remifentanil dose for lightwand intubation without muscle
      relaxants.

PMID- 23549125
TI  - Pupillometry to detect pain response during general anaesthesia following
      unilateral popliteal sciatic nerve block: a prospective, observational study.
AB  - CONTEXT: Pupillary reflex dilation appears to be a reliable indicator of response
      to noxious stimulation even under general anaesthesia. The ability of
      pupillometry to detect the effects of extremity blocks during continuous infusion
      of opioids remains unknown. OBJECTIVE: To explore the performance of pupillometry
      to detect differences in pupillary reflex dilation response to a standardised
      noxious stimulus applied to each leg following unilateral popliteal sciatic nerve
      block during continuous infusion of remifentanil. DESIGN: Prospective,
      observational study. SETTING: University hospital anaesthesia department, between
      June 2010 and December 2010. PATIENTS: Twenty-four adult patients undergoing
      elective foot or ankle surgery under general anaesthesia who requested a
      peripheral nerve block. Unilateral popliteal sciatic nerve block with 0.75%
      ropivacaine and 1% lidocaine was performed awake. General anaesthesia was
      maintained with steady-state infusions of propofol and remifentanil. MAIN OUTCOME
      MEASURE: Video-based pupillometer was used to determine pupillary reflex dilation
      during tetanic stimulation (60 m, 100 Hz) applied to the skin area innervated by
      the sciatic nerve for 5 s after the onset of general anaesthesia. RESULTS:
      Sensory nerve block led to a blunted maximal pupillary reflex dilation response
      to noxious stimulation compared with the non-blocked leg: median (interquartile
      range) change from baseline 2% (1 to 4%) versus 17% (13 to 24%), respectively (P
      < 0.01). The differences in the response persisted throughout the 5-s stimulus
      and the recovery phase. CONCLUSION: These results are a proof of concept. The
      effects of peripheral nerve block can be detected via the measurement of
      pupillary reflex dilation response to noxious stimulation of the skin in patients
      receiving remifentanil.

PMID- 23549126
TI  - Anaesthesia and orphan disease: traumatic cardiac arrest in a patient with
      osteogenesis imperfecta.

PMID- 23549127
TI  - Correlation between cross-sectional area of the internal jugular vein and central
      venous pressure: an observational clinical study.

PMID- 23549128
TI  - A comparison of noninvasive bioreactance with oesophageal Doppler estimation of
      stroke volume during open abdominal surgery: an observational study.
AB  - CONTEXT: The anaesthetist must maintain tissue perfusion by ensuring optimal
      perioperative fluid balance. This can be achieved using less invasive cardiac
      output monitors such as oesophageal Doppler monitoring (ODM). Other less invasive
      cardiac output monitors using bio-impedence technology (noninvasive cardiac
      output monitoring, NICOM) may have a role in monitoring the circulation and
      informing fluid management decisions. OBJECTIVE: To compare estimates of stroke
      volume from ODM with those from NICOM, a noninvasive monitor using bioreactance,
      a modification of transthoracic bio-impedence. DESIGN: An observational study.
      SETTING: Manchester Royal Infirmary, UK. Data collected in 2011 and 2012.
      PARTICIPANTS: Twenty-two patients scheduled for major, open abdominal surgery.
      Reasons for noninclusion: atrial fibrillation; heart failure; oesophageal
      disease; lack of capacity; and known sensitivity to colloid. INTERVENTION: All
      patients had oesophageal Doppler cardiac output monitoring as a standard element
      of anaesthesia care. We placed NICOM Bioreactance electrodes and recorded stroke
      volume estimates from both devices. Fluid challenges were given by the
      anaesthetist and the haemodynamic responses were recorded. MAIN OUTCOME MEASURE:
      Stroke volume during surgery. The Bland-Altman method was used to compare bias
      and limits of agreement for stroke volume and cardiac output. Fluid responders
      were defined as patients who increased stroke volume by at least 10% after fluid
      loading. The precision of each device was calculated during periods of
      haemodynamic stability. RESULTS: We made 788 acceptable measurements of cardiac
      output. The bias was -6.9 ml and the limits of agreement were -22.9 to 36.8 ml.
      The percentage error was 57%. Average precision for both the ODM and NICOM were
      similar, 8.5% (SD 5.4%) and 8.7% (SD 3.2%). The concordance for the stroke volume
      change following fluid challenge was 90.5%. Both devices produced unacceptable
      readings with electrical diathermy. CONCLUSION: Simultaneous stroke volume
      estimations made by noninvasive Bioreactance (NICOM) and oesophageal Doppler
      showed bias and limits of agreement that are not clinically acceptable. The
      measurements made by these two devices cannot be regarded as interchangeable.

PMID- 23549130
TI  - In situ amination and side group effect of multifunctional heterocyclic thione
      ligand toward discrete and polymeric cluster constructions.
AB  - Three metal complexes [Cu(I)6(atdm)6] (1), [Cu(I)(Hatd)(H2atd)] (2) and
      [H3O][Co(II)4Co(III)2Cl3(atd)6].H2O (3) [atdm = 4-dimethylamino-6-anilino-1,3,5
      triazine-2-thiolate, H2atd = 6-anilino-1,3,5-triazine-2,4-dithiol, atdH2 = 6
      anilino-1,3,5-triazine-2,4(1H,3H)-dithione] have been solvothermally synthesized.
      The luminescent complexes 1 and 2 provide remarkable structural diversity
      depending on different reaction solutions. Complex 1 consists of a discrete
      pseudohexagonal prismatic [Cu6S6] core that can be described as two stacked,
      chair-shaped [Cu3S3] rings bound together by the C-N bridges of the atdm ligands,
      in which the atdm ligand was generated via in situ amination of H2atd in the
      presence of DMF solution. Whereas complex 2 is a 2D (4,4) net based on single
      node Cu(I) ions crystallized in acetonitrile, in which H2atd ligands exist in the
      thione form atdH2 and the partially deprotonated form atdH. Complex 3 has a two
      fold interpenetrated (10,3)-a topological network based on unprecedented cobalt
      centered trigonal-bipyramidal [Co6(atd)6] building blocks, linked by Cl(-) double
      bridges and showing oriented effects of aniline side groups. IR spectra,
      elemental analyses and XRD analyses confirmed the phase-purities of the as
      synthesized complexes. The photoluminescence properties of 1 and 2 in the solid
      state and the magnetic properties of 3 are investigated. A discussion of the
      crystal structures, as well as the coordination properties of the multifunctional
      sulfur-containing ligands upon different geometries of the central units, is also
      provided.

PMID- 23549129
TI  - Correlations between pharmacokinetics of IgG antibodies in primates vs. FcRn
      transgenic mice reveal a rodent model with predictive capabilities.
AB  - Transgenic mice expressing human neonatal Fc receptor (FcRn) instead of mouse
      FcRn are available for IgG antibody pharmacokinetic (PK) studies. Given the
      interest in a rodent model that offers reliable predictions of antibody PK in
      monkeys and humans, we set out to test whether the PK of IgG antibodies in such
      mice correlated with the PK of the same antibodies in primates. We began by using
      a single research antibody to study the influence of: (1) different transgenic
      mouse lines that differ in FcRn transgene expression; (2) homozygous vs.
      hemizygous FcRn transgenic mice; (3) the presence vs. absence of coinjected high
      dose human intravenous immunoglobulin (IVIG), and (4) the presence vs. absence of
      coinjected high-dose human serum albumin (HSA). Results of those studies
      suggested that use of hemizygous Tg32 mice (Tg32 hemi) not treated with IVIG or
      HSA offered potential as a predictive model for PK in humans. Mouse PK studies
      were then done under those conditions with a panel of test antibodies whose PK in
      mice and primates is not significantly affected by target binding, and for which
      monkey or human PK data were readily available. Results from the studies revealed
      significant correlations between terminal half-life or clearance values observed
      in the mice and the corresponding values reported in humans. A significant
      relationship in clearance values between mice and monkeys was also observed.
      These correlations suggest that the Tg32 hemi mouse model, which is both
      convenient and cost-effective, can offer value in predicting antibody half-life
      and clearance in primates. 

PMID- 23549131
TI  - Thrombolysis despite recent stroke: a case series.
AB  - BACKGROUND AND PURPOSE: Thrombolysis in ischemic stroke is contraindicated in
      patients who have had a stroke within 3 months. However, it is unclear whether
      thrombolytic therapy is associated with adverse outcomes in this population. We
      report the characteristics and outcomes of patients treated with systemic
      recombinant tissue-type plasminogen activator in the context of known or unknown
      recent stroke. METHODS: We identified patients who received recombinant tissue
      type plasminogen activator despite recent stroke (within 3 months of acute
      thrombolysis). Clinical and radiological findings were collected, including early
      neurological worsening and hemorrhagic transformation on unenhanced computed
      tomography at 24 hours. Clinical outcome measured by modified Rankin Scale was
      determined at 3 months from onset. RESULTS: Six patients presenting with acute
      stroke within 3 months of previous stroke were identified (median age, 76 years;
      median National Institutes of Health Stroke Scale, 8.5). Hemorrhagic
      transformation was seen in the follow-up computed tomography scan in 3 of 6
      cases: all were hemorrhagic transformation 1 (petechial hemorrhage),
      asymptomatic, and mostly located within the area of subacute infarction. There
      was no early neurological deterioration, and 3 patients had modified Rankin Scale
      <= 2 after 3 months. CONCLUSIONS: In our center, we thrombolysed 6 patients
      despite recent stroke. Three patients had asymptomatic petechial hemorrhagic
      transformation within the area of subacute infarct, without apparent neurological
      worsening. Prospective studies are needed to explore the possible safety of
      tissue-type plasminogen activator in the context of previous subacute stroke in
      otherwise eligible patients.

PMID- 23549132
TI  - Favorable vascular profile is an independent predictor of outcome: a post hoc
      analysis of the safety and efficacy of NeuroFlo Technology in Ischemic Stroke
      trial.
AB  - BACKGROUND AND PURPOSE: We hypothesized that a favorable vascular profile (FVP)
      defined as anatomic intactness of the Circle of Willis combined with a stable
      cerebral perfusion pressure (mean arterial blood pressure>65 mm Hg) is a
      prerequisite for collateral recruitment and maintenance and may improve outcome.
      We performed post hoc analyses of a subset of the Safety and Efficacy of NeuroFlo
      Technology in Ischemic Stroke (SENTIS) trial data set to identify whether FVP is
      associated with independent outcome. METHODS: SENTIS was a randomized, controlled
      device trial comparing hemodynamic augmentation with the NeuroFlo device to best
      medical treatment. We identified all patients from the primary dataset (n=515
      patients) with available intracranial vascular imaging at baseline. Vascular
      imaging data were read blind to clinical and treatment data. We performed
      univariate and multivariate analyses to identify predictors of independent
      outcome (modified Rankin Scale 0-2) at 90 days. RESULTS: A total of 192/515
      SENTIS subjects had available baseline vascular imaging (91 treated/101
      controls). Baseline characteristics did not differ between groups. Overall, FVP
      was seen in 89.6% of patients and predicted independent outcome in univariate
      (odds ratio, 7.46; 95% confidence interval, 1.68-33.18; P=0.0082) and multiple
      logistic regression analyses (odds ratio, 10.22; 95% confidence interval, 1.78
      58.57; P=0.0091). Aside from FVP, only baseline National Institutes of Health
      Stroke Scales (NIHSS; odds ratio, 0.74; 95% confidence interval, 0.67-0.82,
      P<0.0001) entered the predictive model. There was no interaction with
      randomization to treatment or control. CONCLUSIONS: FVP and baseline NIHSS
      independently predicted outcome in this subset of the SENTIS population. FVP is a
      novel parameter to predict outcome of acute stroke patients and further studies
      will establish its potential role for selection of optimal candidates for
      hemodynamic augmentation. Clinical Trial Registration Information- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00119717.

PMID- 23549133
TI  - Obesity and the risk of intracerebral hemorrhage: the multicenter study on
      cerebral hemorrhage in Italy.
AB  - BACKGROUND AND PURPOSE: The effect of obesity on the risk of intracerebral
      hemorrhage (ICH) may depend on the pathophysiology of vessel damage. To further
      address this issue, we investigated and quantified the correlations between
      obesity and obesity-related conditions in the causal pathways leading to ICH.
      METHODS: A total of 777 ICH cases >= 55 years of age (287 lobar ICH and 490 deep
      ICH) were consecutively enrolled as part of the Multicenter Study on Cerebral
      Hemorrhage in Italy and compared with 2083 control subjects by a multivariate
      path analysis model. Separate analyses were conducted for deep and lobar ICH.
      RESULTS: Obesity was not independently associated with an increased risk of lobar
      ICH (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-1.01) or deep ICH
      (OR, 1.18; 95% CI, 0.95-1.45) when compared with control subjects. The path
      analysis confirmed the nonsignificant total effect of obesity on the risk of
      lobar ICH (OR, 0.77; 95% CI, 0.58-1.02) but demonstrated a significant indirect
      effect on the risk of deep ICH (OR, 1.28; 95% CI, 1.03-1.57), mostly determined
      by hypertension (OR, 1.07; 95% CI, 1.04-1.11) and diabetes mellitus (OR, 1.04;
      95% CI, 1.01-1.07). Obesity was also associated with an increased risk of deep
      ICH when compared with lobar ICH (OR, 1.62; 95% CI, 1.14-2.31). CONCLUSIONS:
      Obesity increases the risk of deep ICH, mostly through an indirect effect on
      hypertension and other intermediate obesity-related comorbidities, but has no
      major influence on the risk of lobar ICH. This supports the hypothesis of
      different, vessel-specific, biological mechanisms underlying the relationship
      between obesity and cerebral hemorrhage.

PMID- 23549134
TI  - Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke
      prevention in atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: To estimate the cost-effectiveness of stroke prevention
      in patients with nonvalvular atrial fibrillation by using novel oral
      anticoagulants apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg compared
      with warfarin. METHODS: A Markov decision-analysis model was constructed using
      data from clinical trials to evaluate lifetime costs and quality-adjusted life
      years of novel oral anticoagulants compared with warfarin. The modeled population
      was a hypothetical cohort of 70-year-old patients with nonvalvular atrial
      fibrillation, increased risk for stroke (CHADS2 >= 1), renal creatinine clearance
      >= 50 mL/min, and no previous contraindications to anticoagulation. The
      willingness-to-pay threshold was $50 000/quality-adjusted life-years gained.
      RESULTS: In the base case, warfarin had the lowest cost of $77 813 (SD, $2223),
      followed by rivaroxaban 20 mg ($78 738 +/- $1852), dabigatran 150 mg ($82 719 +/-
      $1959), and apixaban 5 mg ($85 326 +/- $1512). Apixaban 5 mg had the highest
      quality-adjusted life-years estimate at 8.47 (SD, 0.06), followed by dabigatran
      150 mg (8.41 +/- 0.07), rivaroxaban 20 mg (8.26 +/- 0.06), and warfarin (7.97 +/-
      0.04). In a Monte Carlo probabilistic sensitivity analysis, apixaban 5 mg,
      dabigatran 150 mg, rivaroxaban 20 mg, and warfarin were cost-effective in 45.1%,
      40%, 14.9%, 0% of the simulations, respectively. CONCLUSIONS: In patients with
      nonvalvular atrial fibrillation and an increased risk of stroke prophylaxis,
      apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg were all cost-effective
      alternatives to warfarin. The cost-effectiveness of novel oral anticoagulantss
      was dependent on therapy pricing in the United States and neurological events
      associated with rivaroxaban 20 mg.

PMID- 23549135
TI  - Letter by Mittal and McCormick regarding article, "self-report of stroke,
      transient ischemic attack, or stroke symptoms and risk of future stroke in the
      REasons for Geographic and Racial Differences in Stroke (REGARDS) study".

PMID- 23549136
TI  - Letter by Kurnik et al regarding article, "antithrombotic therapy and bleeding
      risk in a prospective cohort study of patients with cerebral cavernous
      malformations".

PMID- 23549137
TI  - Efficacy of a new tonic containing urea, lactate, polidocanol, and glycyrrhiza
      inflata root extract in the treatment of a dry, itchy, and subclinically inflamed
      scalp.
AB  - BACKGROUND/AIMS: Dry, itchy and inflamed scalp conditions are common and often
      associated with diseases such as atopic dermatitis or psoriasis. To improve these
      symptoms, we investigated the efficacy of a new tonic containing the active
      ingredients urea, lactate, polidocanol, and Glycyrrhiza inflata root extract,
      containing licochalcone A. STUDY DESIGN/METHODS: 30 subjects with dry and itchy
      scalp conditions underwent a randomized half-head study for 4 weeks, applying the
      leave-on tonic three times a week on one side of the scalp. Tonic effects on skin
      hydration, itching, lipids, microinflammation, and substantivity of tonic
      compounds were determined using corneometry, middle-infrared spectroscopy, direct
      analysis in real-time mass spectrometry, and enzyme-linked immunosorbent assay.
      Volunteers performed a self-assessment; changes in scalp condition were
      documented by in vivo microscopy. RESULTS: After tonic treatment, scalp moisture
      was significantly increased, whereas scalp itching and tautness were
      significantly reduced. Results also demonstrated a high substantivity of urea and
      lactate on the scalp, an increase in triglyceride, and a decrease in free fatty
      acid levels. The amount of total lipids was unchanged. Analyses of scalp wash-ups
      verified a significant reduction in important pro-inflammatory markers.
      CONCLUSION: Due to the actives urea, lactate, polidocanol, and the anti
      inflammatory licochalcone A, the new scalp tonic exhibited excellent performance
      in alleviating scalp dryness, itching, microinflammation, and in normalizing
      disturbances of scalp lipids.

PMID- 23549138
TI  - Postsynthetic processing of copper hydroxide-silica tubes.
AB  - Using reaction conditions far from equilibrium, we produce hollow tubes of silica
      supported Cu(OH)2. The samples are then processed postsynthetically without
      compromising the macroscopic tubular structure. We specifically induce an
      amorphous-crystalline transition and demonstrate the sequential conversion of
      Cu(OH)2 to CuO, Cu2O, and metallic copper using thermal treatment and wet
      chemistry.

PMID- 23549139
TI  - Homogeneous thermal cloak with constant conductivity and tunable heat
      localization.
AB  - Invisible cloak has long captivated the popular conjecture and attracted
      intensive research in various communities of wave dynamics, e.g., optics,
      electromagnetics, acoustics, etc. However, their inhomogeneous and extreme
      parameters imposed by transformation-optic method will usually require
      challenging realization with metamaterials, resulting in narrow bandwidth, loss,
      polarization-dependence, etc. In this paper, we demonstrate that thermodynamic
      cloak can be achieved with homogeneous and finite conductivity only employing
      naturally available materials. It is demonstrated that the thermal localization
      inside the coating layer can be tuned and controlled robustly by anisotropy,
      which enables an incomplete cloak to function perfectly. Practical realization of
      such homogeneous thermal cloak has been suggested by using two naturally
      occurring conductive materials, which provides an unprecedentedly plausible way
      to flexibly realize thermal cloak and manipulate heat flow with phonons.

PMID- 23549143
TI  - Erich Harnack (1852-1915) and a short history of apomorphine.
AB  - Apomorphine, now established as an efficacious therapy for refractory motor
      fluctuations in levodopa-treated Parkinson's disease, has a long and chequered
      history in medical and veterinary therapeutics. The preclinical in vivo
      pharmacological effects of apomorphine were first studied about 150 years ago
      following which the drug was introduced for the treatment of behavioural vices in
      domesticated animals. Erich Harnack's early pharmacological studies in Dorpat
      (now Tartu, Estonia), where he belonged to the pharmacological dynasty of
      Buchheim and Schmiedeberg, are of particular historical significance as he
      emphasised that while apomorphine had potent emetic effects, the drug also had
      complex effects on the central nervous system.

PMID- 23549144
TI  - Charge transfer in cross conjugated 4,8-dithienylbenzo[1,2-b:4,5-b']dithiophene
      based organic sensitizers.
AB  - Two novel cross-conjugated isomers based on 4,8-dithienylbenzo[1,2-b:4,5
      b']dithiophene have been designed and successfully synthesized. It was found that
      the charge transfer interaction was much stronger in the benzodithiophene
      direction as compared with the other perpendicular direction.

PMID- 23549145
TI  - Cytochrome P450-3A phenotyping using midazolam is not altered by OATP1B1
      polymorphisms.

PMID- 23549146
TI  - Seeking the wisdom of crowds through challenge-based competitions in biomedical
      research.
AB  - "Challenge-based competitions" refers to a framework for addressing fundamental
      research questions in which the community is presented with a challenge, the data
      to address the challenge, and independent, unbiased assessment to rank submitted
      solutions. Although the typical result of such efforts is a robust performance
      evaluation of diverse methodologies, challenge-based competitions reach far
      beyond algorithm assessment. Here, we discuss the impact of challenge-based
      competitions in the areas of organizing and building communities and driving
      innovation.

PMID- 23549147
TI  - A cell simulator platform: the cell collective.
AB  - Diseases are often a result of multiple malfunctions in complex, nonlinear
      biological/biochemical networks. As such, these processes are far more
      complicated to understand because they tend to give rise to functions that are
      emergent in nature, i.e., higher-level (mal)functions that are more than the sum
      of their parts. Systems biology provides a new approach to understanding
      biological systems and diseases from a holistic perspective.

PMID- 23549148
TI  - The cost-effectiveness of periodic safety update reports for biologicals in
      Europe.
AB  - We analyzed the cost-effectiveness of all Periodic Safety Update Reports (PSURs)
      submitted for biologicals in Europe from 1995 to 2009 by comparing two regulatory
      scenarios: full regulation (PSUR reporting) and limited regulation (no PSUR
      reporting, but all other parts of the pharmacovigilance framework remain in
      place). During this period, PSUR reporting resulted in the detection of 2 out of
      a total of 24 urgent safety issues for biologicals: (i) distant spread of
      botulinum toxin and (ii) edema/fluid collection associated with off-label use of
      dibotermin-alfa. We used Markov-chain life tables to calculate costs and health
      effects of PSURs. The incremental cost-effectiveness ratio (ICER) of full
      regulation (PSUR reporting) vs. limited regulation (no PSUR reporting) for the
      base-case scenario was ?[euro]342,110 per quality-adjusted life year (QALY)
      gained. It is possible to assess the cost-effectiveness of regulatory
      requirements using the same methods as those used in assessing the cost
      effectiveness of medical interventions.

PMID- 23549149
TI  - Gatekeepers and enablers: how drug regulators respond to a challenging and
      changing environment by moving toward a proactive attitude.
AB  - This article analyzes the role of regulatory authorities in facilitating
      innovation in the pharmaceutical sector. We describe how regulators are expanding
      their role to be not only gatekeepers but also enablers of development. They have
      already responded to the challenging and changing environment by moving toward a
      proactive attitude beyond evaluation of products, thereby more actively
      contributing to their development. Regulators have to continuously evolve their
      knowledge and standards alongside evolution in science. Creation of supportive
      regulatory frameworks and multistakeholder interaction will help address unmet
      regulatory needs.

PMID- 23549150
TI  - Nonsteroidal anti-inflammatory drug use and the risk of melanoma: a meta
      analysis.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have emerged as
      potential chemopreventive agents for melanoma. However, the clinical studies have
      provided contradictory results as to whether NSAIDs reduce the risk of melanoma.
      Our aim was to assess this association through a detailed meta-analysis of the
      studies on the subject published in the peer-reviewed literature. Relevant
      studies were identified by searching PubMed, EMBASE and Web of Science electronic
      databases up to July 2012. Reference lists from retrieved articles were also
      reviewed. Pooled relative risk (RR) estimates and corresponding 95% confidence
      intervals (CIs) were calculated using the fixed-effects or the random-effects
      models on the basis of heterogeneity analysis. Subgroup analyses were carried out
      where data were available. Ten studies involving 490 322 participants contributed
      to the meta-analysis. The summary RR estimate on the basis of all studies did not
      indicate that overall NSAIDs use significantly decreases the risk of melanoma
      (RR=0.94; 95% CI, 0.86-1.03). The use of neither aspirin (RR=0.96; 95% CI, 0.89
      1.03) nor nonaspirin NSAIDs (RR=1.05; 95% CI, 0.96-1.14) was associated with the
      risk of melanoma. Similar results were obtained in the subgroup analyses of
      cohort studies (RR=1.03; 95% CI, 0.95-1.13), high-intensity NSAID use (the
      highest dose of NSAID use reported by included studies, RR=1.05; 95% CI, 0.79
      1.40), and long-term NSAID use (longest duration of NSAID use reported by
      included studies, RR=0.87; 95% CI, 0.66-1.14). However, a slight reduction in the
      risk of melanoma by taking NSAIDs was observed in case-control studies (RR=0.86;
      95% CI, 0.80-0.93). In conclusion, the results of our meta-analysis did not
      indicate that the use of NSAIDs or aspirin is associated with the risk of
      melanoma. More and in-depth research should focus on those problems in the
      future. 

PMID- 23549151
TI  - Randomized controlled trials investigating the role of allergen exposure in food
      allergy: where are we now?
AB  - PURPOSE OF REVIEW: The dramatic increase in food allergy stresses the need for
      more definitive treatment strategies that induce lasting oral tolerance in tandem
      with more effective approaches to primary prevention. Allergen-induced oral
      tolerance is now of prime interest in both of these settings as a potentially
      more effective approach to traditional avoidance strategies. Here, we review the
      recent randomized controlled trials (RCTs) examining the controlled allergen
      exposure in both treatment and prevention of food allergy. RECENT FINDINGS:
      Collectively, RCTs of oral immunotherapy (OIT) for the treatment of food allergy
      increase the amount of food allergen that can be tolerated. Allergic side-effects
      are common and this remains a major obstacle to general use in clinical practice.
      There are also at least eight RCTs currently in progress investigating early
      allergen exposure for the primary prevention of food allergy. SUMMARY: OIT is
      showing promise as a possible treatment for food allergy; however, more large,
      longitudinal studies are needed to optimize both safety and efficacy and to
      assess the long-term effects, before this can be considered in clinical practice.
      The results of the primary prevention studies will be of great importance in
      determining the role of earlier introduction of allergenic foods in reducing the
      burden of food allergy.

PMID- 23549152
TI  - Diversity of intestinal microbiota in infancy and the risk of allergic disease in
      childhood.
AB  - PURPOSE OF REVIEW: Numerous studies have attempted to describe specific
      microbiota deviations that may precede atopic sensitization and atopic disease in
      childhood. This has given rise to a hypothesis suggesting that a reduced
      intestinal microbial diversity in infancy increases the risk of allergic
      manifestations. This review intends to sum up the main findings and discuss
      relevant exposures that regulate intestinal microbial diversity. RECENT FINDINGS:
      Taken together the three studies in this review lend support to the diversity
      hypothesis, but reported differences related to atopic sensitization and clinical
      expression are discussed. A summary on analytic methods and functional aspect of
      the microbiota in allergic disease is presented to ameliorate a presentation of
      recent articles on environmental and host-factors regulating microbiota
      composition and diversity. SUMMARY: The current evidence indicates that
      intestinal microbiota diversity can be associated with allergic diseases, but the
      exact mechanisms and interactions contributing to this effect are far from
      understood and need further investigation.

PMID- 23549153
TI  - Are results of environmental exposure units transferable to real-life exposure?
AB  - PURPOSE OF REVIEW: To reflect on and discuss the recent evidence of reliability
      of the challenge chamber results for real life, especially focusing on the
      validation of allergen concentrations being 'physiologic' and generating symptoms
      in the exposed volunteers comparable to the natural exposure during pollen season
      and to the home environment. RECENT FINDINGS: Publications of the last 18 months
      covered by this review focus on the validation of allergen chamber systems,
      especially on the quantitative comparison of environmental allergen exposure with
      allergen challenge chamber (ACC) exposure. It highlights new evidence on the
      question of relevance of environmental and experimental priming effects and
      discusses the selection of relevant parameters for the quantification of
      treatment effects. SUMMARY: Benchmarks for validating the ACC systems have been
      defined and are referred to in clinical ACC trials in increasing amount. So the
      level of evidence concerning the validity and reliability of allergen chamber
      systems is steadily growing, especially in allergen-specific models, priming
      effects and reproducibility of results in the same study population at different
      time points and with different challenge systems.

PMID- 23549154
TI  - Food allergy: the perspectives of prevention using vitamin D.
AB  - PURPOSE OF REVIEW: We reviewed the scientific publications in the last 2 years on
      the connections between vitamin D and food allergy, and endeavor to focus on the
      possible indications for supplementation in order to prevent allergies. RECENT
      FINDINGS: Ecological studies have suggested a possible relationship between sun
      exposure and atopic diseases such as asthma, atopic dermatitis and anaphylaxis.
      However, no direct evaluation of vitamin D status has been performed. Recent
      studies evaluating the relationship with vitamin D levels at birth or during
      pregnancy have shown conflicting results with the lower levels of vitamin D
      associated with eczema, the higher with increased food allergy prevalence.
      SUMMARY: Although the role of vitamin D in extraskeletal function is certainly
      intriguing and must not be underestimated, at the moment there is a lack of
      consistent data addressing the topic of vitamin D supplementation in the
      prevention of food allergies. However, in light of the vast amount of literature
      regarding the mechanisms connected with atopic diseases, an evaluation of serum
      levels of vitamin D and eventually supplementation must be considered as a
      further opportunity to understand and treat atopic diseases. In this regard, well
      designed trials on vitamin D supplementation to prevent food allergies are
      urgently needed.

PMID- 23549156
TI  - Alcohol, liver, systemic inflammation and skin: a focus on patients with
      psoriasis.
AB  - Emerging evidence suggests that excessive alcohol consumption is associated with
      psoriasis. In alcoholics, antipsoriatic treatments are less efficient, but more
      toxic and an additional challenge is poor therapeutic compliance. There is a
      correlation between excess alcohol intake and increased risk of infections, but
      on the other hand alcohol and its metabolites can trigger a persistent systemic
      inflammation, mediated by pro-inflammatory cytokines released from activated
      Kupffer cells in the liver and from monocytes in the circulation. Ethanol and its
      metabolites can also enhance lymphocyte and keratinocyte activation and
      proliferation and can increase the mRNA levels of genes characteristic for
      proliferating keratinocytes. In this review, we discuss the mechanisms by which
      alcohol contributes to psoriasis development focusing on liver, systemic
      inflammation and skin. 

PMID- 23549155
TI  - A novel in vivo method for isolating antibodies from a phage display library by
      neuronal retrograde transport selectively yields antibodies against p75(NTR.).
AB  - The neurotrophin receptor p75(NTR) is utilized by a variety of pathogens to gain
      entry into the central nervous system (CNS). We tested if this entry portal might
      be exploited using a phage display library to isolate internalizing antibodies
      that target the CNS in vivo. By applying a phage library that expressed human
      single chain variable fragment (scFv) antibodies on their surface to a transected
      sciatic nerve, we showed that (1) phage conjugated to anti-p75(NTR) antibody or
      phage scFv library pre-panned against p75(NTR) are internalized by neurons
      expressing p75(NTR); (2) subsequent retrograde axonal transport separates
      internalized phage from the applied phage; and, (3) internalized phage can be
      recovered from a proximal ligature made on a nerve. This approach resulted in 13
      fold increase in the number of phage isolated from the injured nerve compared
      with the starting population, and isolation of 18 unique internalizing p75(NTR)
      antibodies that were transported from the peripheral nerve into the spinal cord,
      through the blood-brain barrier. In addition, antibodies recognizing other
      potentially internalized antigens were identified through in vivo selection using
      a fully diverse library. Because p75(NTR) expression is upregulated in motor
      neurons in response to injury and in disease, the p75(NTR) antibodies may have
      substantial potential for cell-targeted drug/gene delivery. In addition, this
      novel selection method provides the potential to generate panels of antibodies
      that could be used to identify further internalization targets, which could aid
      drug delivery across the blood-brain barrier. 

PMID- 23549157
TI  - New cyclotetrasiloxanes bearing sila-alkyl substituted side chains and their
      applications as templates for gold nanowires.
AB  - New sila-alkyl substituted cyclotetrasiloxanes, [RMe2SiCH2CH2(Me)SiO]4 [R =
      Ph(1), 2-thienyl(2), 2-furyl(3)] have been synthesized by a hydrosilylation
      reaction between 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane,
      (D4(Vi)) and dimethylphenylsilane/dimethyl-2-thienylsilane/dimethyl-2-furylsilane
      in the presence of Karstedt's catalyst. X-ray crystallographic studies of 1 and 2
      reveal all-trans conformation of the methyl groups bonded to puckered siloxane
      core and formation of 3D supramolecular assemblies by virtue of intermolecular C
      H...pi interactions. These siloxanes act as potential templates for expeditious
      one pot synthesis of gold nanowires of varying aspect ratios which are obtained
      by reduction of HAuCl4.3H2O with triethylsilane (CHCl3, RT). On the other hand,
      the use of linear polysiloxane, [2-ThMe2SiCH2CH2(Me)SiO]n (4) in lieu of the
      cyclosiloxane 2 affords predominant formation of polydispersed AuNPs along with a
      few extended structures. These results suggest that conformational confinement of
      the appended groups on the cyclosiloxanes, 1-3 plays an important role to impart
      morphological control of the gold nanowire assemblies.

PMID- 23549158
TI  - Gold nanoparticles disrupt zebrafish eye development and pigmentation.
AB  - Systematic toxicological study is still required to fully understand the hazard
      potentials of gold nanoparticles (AuNPs). Because their biomedical applications
      are rapidly evolving, we investigated developmental toxicity of AuNPs in an in
      vivo embryonic zebrafish model at exposure concentration ranges from 0.08 to
      50mg/l. Exposure of zebrafish embryos to 1.3 nm AuNPs functionalized with a
      cationic ligand, N,N,N-trimethylammoniumethanethiol (TMAT-AuNPs), resulted in
      smaller malpigmented eyes. We determined that TMAT-AuNPs caused a significant
      increase of cell death in the eye, which was correlated with an increase in gene
      expression of p53 and bax. Expression patterns of key transcription factors
      regulating eye development (pax6a, pax6b, otx2, and rx1) and pigmentation (sox10)
      were both repressed in a concentration-dependent manner in embryos exposed to
      TMAT-AuNPs. Reduced spatial localization of pax6a, rx1, sox10, and mitfa was
      observed in embryos by whole-mount in situ hybridization. The swimming behavior
      of embryos exposed to sublethal concentrations of TMAT-AuNPs showed hypoactivity,
      and embryos exhibited axonal growth inhibition. Overall, these results
      demonstrated that TMAT-AuNPs disrupt the progression of eye development and
      pigmentation that continues to behavioral and neuronal damage in the developing
      zebrafish.

PMID- 23549159
TI  - All-optical signal processing using dynamic Brillouin gratings.
AB  - The manipulation of dynamic Brillouin gratings in optical fibers is demonstrated
      to be an extremely flexible technique to achieve, with a single experimental
      setup, several all-optical signal processing functions. In particular, all
      optical time differentiation, time integration and true time reversal are
      theoretically predicted, and then numerically and experimentally demonstrated.
      The technique can be exploited to process both photonic and ultra-wide band
      microwave signals, so enabling many applications in photonics and in radio
      science.

PMID- 23549161
TI  - Mechanical thrombectomy with the solitaire stent at Lyon, France.
AB  - BACKGROUND/AIMS: The Solitaire stent has been suggested as a promising device to
      perform intracranial thrombectomy in large vessels. We report our experience.
      METHODS: Consecutive patients in whom a thrombectomy with Solitaire stent had
      been performed for acute ischemic stroke in the Lyon Stroke Unit, France, from
      November 2009 to November 2010 were enrolled. RESULTS: There were 12 patients
      with a mean age of 66 years and a mean baseline National Institutes of Health
      Stroke Scale score of 17.5. There were 10 cases of anterior cerebral artery and 2
      cases of basilar artery occlusion. The mean time from onset of symptoms to
      recanalization was 306 min. Partial or total recanalization was obtained in 91.6%
      of patients. One case of periprocedural asymptomatic arterial dissection and 1
      case of symptomatic cerebral hemorrhage occurred. At 90 days, 4 patients (33.3%)
      were dead and 5 patients (41.6%) had a modified Rankin Scale <=2. CONCLUSIONS: In
      this case series, thrombectomy using Solitaire stent in stroke related to large
      vessel occlusion appears to be feasible, safe and potentially effective.
      Randomized controlled trials are needed to demonstrate the superiority of
      thrombectomy alone or in combination with intravenous tPA over intravenous tPA
      alone in ischemic stroke patients with large intracranial arterial occlusion.

PMID- 23549162
TI  - Specific many-electron effects in X-ray spectra of simple metals and graphene.
AB  - In this work the influence of many-electron effects on the shape of
      characteristic X-ray emission bands of the simple metals Mg and Al is examined by
      means of ab initio calculations and semi-empirical models. These approaches are
      also used for the analysis of C K-emission and absorption spectra of graphene.
      Both the dynamical screening of the core vacancy and the Auger-effect in the
      valence band (VB) have been taken into account. Dynamical screening of the core
      vacancy by valence electrons (the so-called MND effect) is considered ab initio
      in the framework of density functional theory. The Auger effect in the VB was
      taken into account within a semi-empirical method, approximating the quadratic
      dependence of the VB hole level width on the difference between the level energy
      and the Fermi energy. All theoretical spectra are in very good agreement with
      available experimental data.

PMID- 23549163
TI  - Electron tunneling from electronically excited states of isolated bisdisulizole
      derived trianion chromophores following UV absorption.
AB  - Photoelectron spectra of isolated [M-BDSZ](3-) (BDSZ = bisdisulizole, M = H, Li,
      Na, K, Cs) triply charged anions exhibit a dominant constant electron kinetic
      energy (KE) detachment feature, independent of detachment wavelengths over a wide
      UV range. Photoelectron imaging spectroscopy shows that this constant KE feature
      displays an angular distribution consistent with delayed rather than direct
      electron emission. Time-resolved pump-probe (388 nm/775 nm) two-colour
      photoelectron spectroscopy reveals that the constant KE feature results from two
      simultaneously populated excited states, which decay at different rates. The
      faster of the two rates is essentially the same for all the [M-BDSZ](3-) species,
      regardless of M. The slower process is associated with lifetimes ranging from
      several picoseconds to tens of picoseconds. The lighter the alkali cation is, the
      longer the lifetime of this state. Quantum chemical calculations indicate that
      the two decaying states are in fact the two lowest singlet excited states of the
      trianions. Each of the two corresponding photoexcitations is associated with
      significant charge transfer. However, electron density is transferred from
      different ends of the roughly chain-like molecule to its aromatic center. The
      energy (and therefore the decay rate) of the longer-lived excited state is found
      to be influenced by polarization effects due to the proximal alkali cation
      complexed to that end of the molecule. Systematic M-dependent geometry changes,
      mainly due to the size of the alkali cation, lead to M-dependent shifts in
      transition energies. At the constant pump wavelength this leads to different
      amounts of vibrational energy in the respective excited state, contributing to
      the variations in decay rates. The current experiments and calculations confirm
      excited state electron tunneling detachment (ESETD) to be the mechanism
      responsible for the observed constant KE feature. The ESETD phenomenon may be
      quite common for isolated multiply charged anions, which are strong fluorophores
      in the condensed phase - making ESETD useful for studies of the transient
      response of such species after electronic excitation.

PMID- 23549164
TI  - Interfacial strain-promoted alkyne-azide cycloaddition (I-SPAAC) for the
      synthesis of nanomaterial hybrids.
AB  - An interfacial strain promoted azide-alkyne cycloaddition (I-SPACC) is introduced
      as a method to prepare robust nanomaterial hybrids. This is demonstrated with a
      reaction between a novel dibenzocyclooctyne-modified single walled carbon
      nanotubes (DBCO-SWCNT) and a versatile water-soluble azide modified gold
      nanoparticle (N3-EG4-AuNP).

PMID- 23549165
TI  - Pseudotumor cerebri in a case of ulcerative colitis with sagittal sinus
      thrombosis.
AB  - BACKGROUND: Thromboembolic events are a known complication of Inflammatory Bowel
      Disease (IBD) especially during disease relapse, more commonly in deep veins of
      extremities and lung, and rarely as Cerebral Sinovenous Thrombosis (CSVT). CASE
      PRESENTATION: We describe an 11 year, old male patient with 3 months history of
      Ulcerative Colitis (UC) who presented as pseudotumor cerebri due to superior
      sagittal sinus thrombosis during an acute exacerbation of his colitis, that was
      successfully treated with heparin and then warfarin. CONCLUSION: In any known
      cases of UC presenting as acute severe headache, consider CSVT and request brain
      MRI and MRV to facilitate the diagnosis and early treatment.

PMID- 23549166
TI  - Lymphatic fate determination: playing RAF with ERK.

PMID- 23549167
TI  - The metabolic facet of pancreatic cancer: how hypoxia shapes fatal cancer cells.

PMID- 23549168
TI  - Induction of TRIF- or MYD88-dependent pathways perturbs cell cycle regulation in
      pancreatic cancer.

PMID- 23549169
TI  - Differences in regulation and function of E-cyclins in human cancer cells.

PMID- 23549170
TI  - Compensation, crosstalk and sequestering: the currency of checkpoints in cancer.

PMID- 23549171
TI  - ATM targets hnRNPK to control p53.

PMID- 23549172
TI  - The Warburg effect version 2.0: metabolic reprogramming of cancer stem cells.
AB  - When fighting cancer, knowledge on metabolism has always been important. Today,
      it matters more than ever. The restricted cataloging of cancer genomes is quite
      unlikely to achieve the task of curing cancer, unless it is integrated into
      metabolic networks that respond to and influence the constantly evolving cancer
      stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had
      pushed the 1920s Otto Warburg's metabolic cancer hypothesis into obscurity for
      decades, the most recent studies begin to support a new developing paradigm, in
      which the molecular logic behind the conversion of non-CSCs into CSCs can be
      better understood in terms of the "metabolic facilitators" and "metabolic
      impediments" that operate as proximate openings and roadblocks, respectively, for
      the transcriptional events and signal transduction programs that ultimately
      orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states.
      Here we propose that a profound understanding of how human carcinomas install a
      proper "Warburg effect version 2.0" allowing them to "run" the CSCs' "software"
      programs should guide a new era of metabolo-genomic-personalized cancer medicine.
      By viewing metabolic reprogramming of CSCs as an essential characteristic that
      allows dynamic, multidimensional and evolving cancer populations to compete
      successfully for their expansion on the organism, we now argue that CSCs
      bioenergetics might be another cancer hallmark. A definitive understanding of
      metabolic reprogramming in CSCs may complement or to some extent replace, the 30
      y-old paradigm of targeting oncogenes to treat human carcinomas, because it can
      be possible to metabolically create non-permissive or "hostile" metabotypes to
      prevent the occurrence of CSC cellular states with tumor- and metastasis
      initiating capacity.

PMID- 23549173
TI  - Evaluation of the potential therapeutic role of a new generation of vitamin D
      analog, MART-10, in human pancreatic cancer cells in vitro and in vivo.
AB  - Pancreatic cancer is a lethal disease with no known effective chemotherapy and
      radiotherapy, and most patients are diagnosed in the late stage, making them
      unsuitable for surgery. Therefore, new therapeutic strategies are urgently
      needed. 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] is known to possess
      antitumor actions in many cancer cells in vitro and in vivo models. However, its
      clinical use is hampered by hypercalcemia. In this study, we investigated the
      effectiveness and safety of a new generation, less calcemic analog of
      1alpha,25(OH)2D3, 19-nor-2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxyvitamin D3
      (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. We
      demonstrate that MART-10 is at least 100-fold more potent than 1alpha,25(OH)2D3
      in inhibiting BxPC-3 cell proliferation in a time- and dose-dependent manner,
      accompanied by a greater upregulation of cyclin-dependent kinase inhibitors p21
      and p27 and a greater downregulation of cyclin D3 and cyclin-dependent kinases 4
      and 5, leading to a greater increase in the fraction of cells in G0/G1 phase. No
      induction of apoptosis and no effect on Cdc25 phosphatases A and C were observed
      in the presence of either MART-10 or 1alpha,25(OH)2D3. In a xenograft mouse
      model, treatment with 0.3 ug/kg body weight of MART-10 twice/week for 3 weeks
      caused a greater suppression of BxPC-3 tumor growth than the same dose of
      1alpha,25(OH)2D3 without inducing hypercalcemia and weight loss. In conclusion,
      MART-10 is a promising agent against pancreatic cancer growth. Further clinical
      trial is warranted.

PMID- 23549175
TI  - RNF8 links nucleosomal and cytoskeletal ubiquitylation of higher order protein
      structures.

PMID- 23549177
TI  - From "big epidemiology" to "colossal epidemiology": when all eggs are in one
      basket.

PMID- 23549174
TI  - Dbf4: the whole is greater than the sum of its parts.
AB  - Together with cyclin-dependent kinases, the Dbf4-dependent kinase (DDK) is
      essential to activate the Mcm2-7 helicase and, hence, initiate DNA replication in
      eukaryotes. Beyond its role as the regulatory subunit of the DDK complex, the
      Dbf4 protein also regulates the activity of other cell cycle kinases to mediate
      the checkpoint response and prevent premature mitotic exit under stress. Two
      features that are unusual in DNA replication proteins characterize Dbf4. The
      first is its evolutionary divergence; the second is how its conserved motifs are
      combined to form distinct functional units. This structural plasticity appears to
      be at odds with the conserved functions of Dbf4. In this review, we summarize
      recent genetic, biochemical and structural work delineating the multiple
      interactions mediated by Dbf4 and its various functions during the cell cycle. We
      also discuss how the limited sequence conservation of Dbf4 may be an advantage to
      regulate the activities of multiple cell cycle kinases.

PMID- 23549178
TI  - The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)
      Consortium as a model of collaborative science.

PMID- 23549179
TI  - Is size the next big thing in epidemiology?

PMID- 23549180
TI  - Commentary: how to report instrumental variable analyses (suggestions welcome).

PMID- 23549181
TI  - Commentary: sodium and blood pressure: never too late to reduce dietary intake.

PMID- 23549182
TI  - The "obesity paradox" explained.

PMID- 23549183
TI  - Reduced quality of life in internet-panel controls.

PMID- 23549184
TI  - Breast cancer and simian virus 40 infection.

PMID- 23549185
TI  - Abdominal fat and male excess of esophageal adenocarcinoma.

PMID- 23549186
TI  - Regression calibration is valid when properly applied.

PMID- 23549187
TI  - Regression calibration is valid when properly applied.

PMID- 23549188
TI  - Cell phone use and crash risk.

PMID- 23549189
TI  - Cell phone use and crash risk.

PMID- 23549190
TI  - Comparing methods for handling missing data.

PMID- 23549191
TI  - Temperature sensitivity in indigenous Australians.

PMID- 23549192
TI  - Is autism linked to migraine aura?

PMID- 23549193
TI  - On sibling designs.

PMID- 23549194
TI  - Blood lead and pediatric asthma.

PMID- 23549196
TI  - Isolated cortical vein thrombosis: a widely variable clinicoradiological
      spectrum.
AB  - BACKGROUND/AIMS: The aim of this study is to highlight the variable
      clincoradiological spectrum of isolated cortical vein thrombosis (ICoVT), which
      seems to remain a challenge to clinicians. CASES REPORTS: We reported 3 patients
      with this diagnosis. One presented with only an epileptic seizure, one with
      worsening headache, seizures, mental disorder, speech disturbance and right-sided
      weakness, and the other with seizures and fluctuating paralysis in her left-sided
      limbs. Brain images were manifested with a strand-like abnormal signal, a large
      hemorrhagic infarction and a continuously enlarged space-occupying massive edema,
      respectively. CONCLUSIONS: Neurologic features and brain imaging of ICoVT are
      highly variable, which might be partly responsible for the underestimation of
      ICoVT. Clinical diagnosis should probably be evoked more often.

PMID- 23549197
TI  - A novel single-site manganese(II) complex of a pyridine derivative as a catalase
      mimetic for disproportionation of H2O2 in water.
AB  - A novel single site Mn(II) complex was successfully synthesized and tested in the
      aqueous disproportionation of hydrogen peroxide. The complex was found to be
      stable (HR-XAS) and exhibits catalase-like activity in neutral pH. Theoretical
      calculations suggested a reaction mechanism involving two complexes, changes in
      metal oxidation state and proton shuttling.

PMID- 23549198
TI  - Practice patterns and outcomes in retransplantation among pediatric kidney
      transplant recipients.
AB  - BACKGROUND: More than 25% of pediatric kidney transplants are lost within 7
      years, necessitating dialysis or retransplantation. Retransplantation practices
      and the outcomes of repeat transplantations, particularly among those with early
      graft loss, are not clear. METHODS: We examined retransplantation practice
      patterns and outcomes in 14,799 pediatric (ages <18 years) patients between 1987
      and 2010. Death-censored graft survival was analyzed using extended Cox models
      and retransplantation using competing risks regression. RESULTS: After the first
      graft failure, 50.4% underwent retransplantation and 12.1% died within 5 years;
      after the second graft failure, 36.1% underwent retransplantation and 15.4% died
      within 5 years. Prior preemptive transplantation and graft loss after 5 years
      were associated with increased rates of retransplantation. Graft loss before 5
      years, older age, non-Caucasian race, public insurance, and increased panel
      reactive antibody were associated with decreased rates of retransplantation.
      First transplants had lower risk of graft loss compared with second (adjusted
      hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.64-0.80; P<0.001),
      third (aHR, 0.62; 95% CI, 0.49-0.78; P<0.001), and fourth (aHR, 0.44; 95% CI,
      0.24-0.78; P=0.005) transplants. However, among patients receiving two or more
      transplants (conditioned on having lost a first transplant), second graft median
      survival was 8.5 years despite a median survival of 4.5 years for the first
      transplant. Among patients receiving three or more transplants, third graft
      median survival was 7.7 years despite median survivals of 2.1 and 3.1 years for
      the first and second transplants. CONCLUSIONS: Among pediatric kidney transplant
      recipients who experience graft loss, racial and socioeconomic disparities exist
      with regard to retransplantation, and excellent graft survival can be achieved
      with retransplantation despite poor survival of previous grafts.

PMID- 23549199
TI  - Chronic pain after childbirth.
AB  - PURPOSE OF REVIEW: Although childbirth is considered a natural event, some
      deliveries may necessitate instrumentation or surgical intervention. In contrast
      with trauma or surgery, persistent pain after delivery has received little
      attention until recently, despite the large number of individuals potentially at
      risk. RECENT FINDINGS: Excluding pre-existing pain or pain that developed during
      pregnancy, prospective studies show a surprisingly low prevalence of persistent
      pain after childbirth, much lower than the prevalence reported in retrospective
      studies and that of persistent postsurgical pain in a general population for
      similar procedures. The nature of persistent pain itself remains poorly
      characterized; the chronic pain following caesarean delivery appears to be
      predominantly neuropathic, but the intensity is generally lower than usually
      reported for other types of chronic neuropathic pain. Finally, the type of
      delivery and the degree of tissue trauma do not seem to impact the risk of
      developing persistent pain. It is unclear whether individual factors place
      specific women at a risk for persistent pain. Experimental study suggests that
      protective mechanisms against the development of neuropathic pain may be active
      during the puerperium, but whether these mechanisms exist following human
      childbirth remains unknown. SUMMARY: Some recent findings on the development of
      persistent pain after childbirth are intriguing and might open the way to
      interesting perspectives for the treatment of persistent pain caused by trauma or
      surgery.

PMID- 23549200
TI  - Body fat in Singaporean infants: development of body fat prediction equations in
      Asian newborns.
AB  - BACKGROUND/OBJECTIVES: Prediction equations are commonly used to estimate body
      fat from anthropometric measurements, but are population specific. We aimed to
      establish and validate a body composition prediction formula for Asian newborns,
      and compared the performance of this formula with that of a published equation.
      SUBJECTS/METHODS: Among 262 neonates (174 from day 0, 88 from days 1-3 post
      delivery) from a prospective cohort study, body composition was measured using
      air-displacement plethysmography (PEA POD), with standard anthropometric
      measurements, including triceps and subscapular skinfolds. Using fat mass
      measurement by PEA POD as a reference, stepwise linear regression was utilized to
      develop a prediction equation in a randomly selected subgroup of 62 infants
      measured on days 1-3, which was then validated in another subgroup of 200 infants
      measured on days 0-3. RESULTS: Regression analyses revealed subscapular
      skinfolds, weight, gender and gestational age were significant predictors of
      neonatal fat mass, explaining 81.1% of the variance, but not triceps skinfold or
      ethnicity. By Bland-Altman analyses, our prediction equation revealed a non
      significant bias with limits of agreement (LOA) similar to those of a published
      equation for infants measured on days 1-3 (95% LOA: (-0.25, 0.26) kg vs (-0.23,
      0.21) kg) and on day 0 (95% LOA: (-0.19, 0.17) kg vs (-0.17, 0.18) kg). The
      published equation, however, exhibited a systematic bias in our sample.
      CONCLUSIONS: Our equation requires only one skinfold site measurement, which can
      significantly reduce time and effort. It does not require the input of ethnicity
      and, thus, aid its application to other Asian neonatal populations.

PMID- 23549201
TI  - Fatty-acid composition of maternal and umbilical cord plasma and early childhood
      atopic eczema in a Spanish cohort.
AB  - BACKGROUND/OBJECTIVES: Fatty-acid status during in-utero development might
      influence the risk of atopic diseases in early childhood. The aim of this work
      was to identify the relationship between maternal plasma and cord blood fatty
      acid (FA) composition and the risk of atopic eczema in the offspring at 14 months
      of age. SUBJECTS/METHODS: Two hundred and eleven non-atopic mothers and their
      children were studied. Mothers were recruited in their first trimester of
      gestation and children were monitored until 14 months of age. Samples of maternal
      plasma and cord blood plasma were analyzed to determine the FA profile of total
      lipids. Presence of atopic eczema in the infants was documented through
      questionnaires at 6 and 14 months of age. RESULTS: Higher concentrations of total
      long-chain polyunsaturated FA (LC-PUFA) were found in maternal plasma of non
      atopic children in relation to atopic group. Moreover, this maternal plasma LC
      PUFA content was negatively correlated with the atopic eczema (odds ratios
      (OR)=0.83, P=0.04) in infants. Regarding cord blood samples, docosahexaenoic acid
      (DHA C22:6n3) and the sum of total n-3 and of LC-PUFA n-3 showed a negative
      correlation with the prevalence of the disease (OR=0.50, 0.49 and 0.49,
      respectively). CONCLUSIONS: Our results show that the fatty-acid status of the
      fetus during pregnancy has an important role in the development of atopic eczema
      in early childhood. The prevalence of this atopic disorder is related to lower
      cord blood plasma levels of FA belonging to n-3 series, especially DHA.

PMID- 23549202
TI  - Severe vitamin C deficiency in a critically ill adult: a case report.
AB  - Scurvy, a severe form of vitamin C deficiency, killed scores of people until its
      cause and treatment were firmly established at the end of the eighteenth century.
      Since then, cases have surged periodically around the world, mostly in developing
      countries and during times of war and famine. In developed countries, scurvy is
      still endemic and evidence is growing that vitamin C deficiency might affect up
      to 30 percent of the population. Low socio-economic status, alcoholism, severe
      psychiatric illness leading to poor nutrition and critical illness are
      significant risk factors. We hereby report the case of a patient admitted in a
      Swiss intensive care unit of a tertiary teaching hospital and presenting with
      clinical signs and symptoms of severe vitamin C deficiency. 

PMID- 23549203
TI  - Malnutrition risk in newly hospitalized overweight and obese individuals: Mr NOI.
AB  - BACKGROUND/OBJECTIVES: Malnutrition risk and its consequences have not been
      reported in obese and overweight newly hospitalized patients. To estimate
      malnutrition risk among newly hospitalized overweight or obese patients, and to
      assess the effect of body mass index (BMI) on duration of hospitalization and
      risk of in-hospital death among hospitalized adults at increased risk of
      malnutrition. SUBJECTS/METHODS: In this survey, all adults newly admitted to
      internal medicine and surgical departments at a large tertiary medical center,
      during the 5-week data acquisition period in 2010, were screened for malnutrition
      risk using the Nutrition Risk Screen (NRS 2002). Malnutrition risk was compared
      across body weight categories. In addition, overweight/obese subjects were
      compared by malnutrition risk category. RESULTS: Of the 431 individuals analyzed,
      138 were overweight and 105 were obese. Among overweight or obese patients, 23.2%
      and 24.8%, respectively, were at increased risk for malnutrition. Elevated risk
      for malnutrition prolonged hospitalization for both overweight and obese patients
      (from 5.6 +/- 7.9 to 10.0 +/- 10.3 days (P=0.04) and from 4.8 +/- 4.6 to 15.1 +/-
      25.7 days (P=0.001), respectively). Prolonged hospital stay remained associated
      with malnutrition risk after controlling for age and BMI. Malnutrition risk
      significantly increased odds of in-hospital death: odds ratio (OR) 6.4, 95%
      confidence interval (CI) 1.2-33.2, P=0.03, even after controlling for age and
      BMI. CONCLUSIONS: Increased malnutrition risk is a frequent finding in newly
      hospitalized overweight/obese adults, prolongs length of hospital stay and
      increases risk of in-hospital mortality.

PMID- 23549204
TI  - Obesity as a showcase for transdisciplinary research.

PMID- 23549205
TI  - Iontophoresis-mediated transdermal permeation of peptide dendrimers across human
      epidermis.
AB  - PURPOSE OF THE STUDY: The overall aim of the present work was to elucidate the
      effects of iontophoresis on assisting permeation/deposition of peptide dendrimers
      across/within human skin. PROCEDURES: A series of peptide dendrimers containing
      arginine and histidine as terminal acids were synthesized and characterized.
      These dendrimers were subjected to passive and iontophoretic permeation studies
      across human epidermis. RESULTS: The synthesized peptide dendrimers were found to
      be stable in epidermal, dermal and skin extracts up to 6 h. Passive diffusion
      studies revealed that none of the synthesized peptide dendrimers permeated human
      epidermis up to 6 h, although minute concentrations of low molecular weight
      dendrimers were detected in receptor medium at the end of 24 h. Application of
      iontophoresis significantly increased the permeation of all the tested peptide
      dendrimers across human skin in a molecular weight-dependent manner compared to
      simple passive diffusion. Electromigration was found to be the dominant mechanism
      behind the iontophoretic permeation of peptide dendrimers across human skin.
      CONCLUSIONS: The present study demonstrates that iontophoresis is an effective
      technique in enhancing the transdermal permeation of peptide dendrimers. MESSAGE
      OF THE PAPER: This study foresees the possibility of applying peptide dendrimers
      in iontophoretic delivery of drugs and macromolecules across/within the skin.

PMID- 23549206
TI  - Dynamic postures of the transverse metacarpal arch during typing.
AB  - The purpose of this paper is to describe the transverse metacarpal arch (TMA)
      during a dynamic typing task. Static/relaxed and dynamic typing TMA were
      collected from 36 right-handed females with musculoskeletal discomfort using a
      motion capture system. While the angle of right TMA static/relaxed posture (10.1
      degrees  +/- 5.5 degrees ) was significantly larger than the left (8.5 degrees 
      +/- 5.6 degrees ) (P < .05), the right dynamic posture (10.6 degrees  +/- 4.3
      degrees ) was not significantly different from the left (10.3 degrees  +/- 5.5
      degrees ) (P = .66). Within both these mean scores, there was considerable
      individual variation, with some subjects demonstrating very flat TMA, and some
      very curved. The results indicate that TMA angular postures both for
      static/relaxed and dynamic typing are highly variable both between individuals
      and between individual hands. 

PMID- 23549207
TI  - Pentafulvene-derived eta3-allyltitanocenes as intermediates for the
      stereoselective functionalization of 5-membered carbocycles.
AB  - Allyltitanocene complexes can be generated by reacting pentafulvenes with DIBAL-H
      and Cp2TiCl2. Their coupling with aldehydes affords homoallylic alcohols in a
      highly regio- and stereoselective manner. The potential of this method for the
      stereoselective synthesis of cyclopentane derivatives is illustrated.

PMID- 23549208
TI  - Electric double-layer capacitance between an ionic liquid and few-layer graphene.
AB  - Ionic-liquid gates have a high carrier density due to their atomically thin
      electric double layer (EDL) and extremely large geometrical capacitance Cg.
      However, a high carrier density in graphene has not been achieved even with ionic
      liquid gates because the EDL capacitance CEDL between the ionic liquid and
      graphene involves the series connection of Cg and the quantum capacitance Cq,
      which is proportional to the density of states. We investigated the variables
      that determine CEDL at the molecular level by varying the number of graphene
      layers n and thereby optimising Cq. The CEDL value is governed by Cq at n < 4,
      and by Cg at n > 4. This transition with n indicates a composite nature for CEDL.
      Our finding clarifies a universal principle that determines capacitance on a
      microscopic scale, and provides nanotechnological perspectives on charge
      accumulation and energy storage using an ultimately thin capacitor.

PMID- 23549209
TI  - Asymmetric organocatalysis mediated by alpha,alpha-L-diaryl prolinols: recent
      advances.
AB  - This feature article illustrates progress in asymmetric organocatalysis achieved
      by using readily available alpha,alpha-L-diaryl prolinols from 2009 up to middle
      2012. This class of bifunctional organocatalysts has shown the ability to
      catalyze a variety of reactions such as epoxidation, cyclopropanation, alpha
      sulfenylation of active methines, cross conjugate addition, direct aldol,
      cycloaddition and desymmetrization reactions. The most striking feature of these
      promoters is to enable either non-covalent or covalent activation of the
      reagents, thus distinguishing themselves as a rare example of organic promoters
      capable of encompassing alternative mechanistic pathways, namely enamine/iminium
      catalysis and Bronsted acid/base catalysis.

PMID- 23549210
TI  - Support for the future of nursing.

PMID- 23549211
TI  - Outpatients with inflammatory bowel disease (IBD) strongly prefer annual
      telephone calls from an IBD nurse instead of outpatient visits.
AB  - With the increasing number of patients with inflammatory bowel disease (IBD) and
      consequently limited available resources, the organization and quality of care
      that patients receive require ongoing attention. Many initiatives have been
      introduced, but few have begun by asking the patients about their support for
      planned changes to their care. The aim of this project was to investigate the
      willingness and concerns of outpatients with IBD to change regular outpatient
      visits to annual telephone calls from an IBD nurse. We also wanted to illuminate
      any potential barriers to introducing self-management (SM) to this population.
      One way to accomplish this is by introducing SM that replaces routine
      appointments in the outpatient clinic with annual blood sample collection,
      followed by a telephone call from an IBD nurse and direct acute access to the
      clinic, if needed. We consecutively included 150 IBD patients who attended the
      outpatient clinic at Aarhus University Hospital, Aarhus C, Denmark. They were
      asked to which extent they were willing to shift to the SM approach from their
      current routine. The survey showed that 87% of the patients agreed to adopt the
      SM approach. Many patients commented that it was an excellent and timesaving
      idea. Those who had doubts were mainly older, retired patients. Their concerns
      were mainly due to hearing loss, disease activity, medical treatment monitoring,
      and worries about the competence of the IBD nurse.

PMID- 23549212
TI  - An overview and evaluation of combining an addiction liaison nurse outpatient
      service with hepatitis C outpatient clinics in Glasgow, Scotland.
AB  - A new purpose-built facility for the care of patients with Hepatitis C was opened
      at Gartnavel General Hospital in Glasgow, Scotland, in 2009, bringing together
      infectious diseases and gastroenterology disciplines. An addiction liaison nurse
      outpatient service was established alongside existing Hepatitis C outpatient
      clinics in October 2010. This service supports staff and patients with Hepatitis
      C and addiction issues. The purpose of this study was to evaluate the usefulness
      of combining the Addiction Liaison Nurse outpatient service with the Hepatitis C
      outpatient clinic. Two methods were used in data collection. A brief
      questionnaire asking staff their view on the addiction liaison service and
      addiction issues with regard to Hepatitis C was distributed and completed by
      personnel assigned to the clinics. Staff were also queried about their view on
      the number and quality of referrals generated by the addiction liaison clinic.
      The results from the questionnaire indicate that staff agreed that patients
      should be abstinent from alcohol and illicit drugs before and during treatment of
      Hepatitis C. Further research is called for with regard to abstinence from
      alcohol and drugs before and during Hepatitis C treatment.

PMID- 23549213
TI  - Evaluation of medically significant bacteria in colonoscopes after 8 weeks of
      shelf life in open air storage.
AB  - The purpose of this study was to examine bacterial growth in colonoscopes in a
      series of graduated shelf times. There is no conclusive evidence on the length of
      time colonoscopes can be safely stored before requiring redisinfection. Standards
      for processing scopes after use are described and supported by the professional
      organizations of gastroenterology and infection control; however, shelf life
      varies from 3 to 5 days and most recommendations are based on clinical consensus.
      In this study, four colonoscopes were used in a clinical procedure, underwent
      automated high-level disinfection with 2.6% buffered glutaraldehyde, and cultured
      after 3, 5, 7, 14, 21, 28, 42, and 56 days of shelf time. Two investigators
      collected all the cultures after interrater reliability was established. Cultures
      were processed in the microbiology laboratory. No medically significant growth
      was detected at any of the culture points. At Day 14 and Day 42, one of four
      scopes grew fewer than two colony-forming units of a medically insignificant
      bacterium. Using professional standards for high-level disinfection growth was
      suppressed for up to 8 weeks. Further evidence to assess fungal or viral growth
      is needed to be able to make suggestions for colonoscope shelf life.

PMID- 23549214
TI  - Improving outcomes for patients receiving transarterial chemoembolization for
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is a cancer with increasing incidence in the veteran
      population. This type of cancer can be treated with transarterial
      chemoembolization, an invasive procedure performed by specially trained
      interventional radiologists. The most common serious complications are liver
      failure, sepsis secondary to ischemic cholecystitis or liver abscess,
      gastrointestinal bleeding, and death. However, nursing staff and physicians often
      have little or no experience in caring for patients in the hospital who have had
      this procedure. Patient safety can be threatened by this lack of knowledge.
      Sources of threat to patient safety are described by the Institute of Medicine as
      falling into 4 categories: management, workforce, work processes, and
      organizational culture. To promote patient safety, defenses need to be deployed
      to address each category. In this article, the author provides a case example,
      describes threats to the patient's safety, and describes a plan to improve the
      care of all patients undergoing this procedure.

PMID- 23549215
TI  - Examination of the effect of BornFree ActiveFlow baby bottles on infant colic.
AB  - Despite its benign, natural course, colic is a significant problem in babies and
      imparts a psychological and physical burden to parents. This study has examined
      the relief of colic symptoms when using BornFree ActiveFlow baby bottles by
      comparing observed symptoms of 30 otherwise healthy newborns (ages 2-21 weeks)
      who had all been diagnosed as having colic symptoms. Twenty of the babies were
      switched to feeding with BornFree bottles (the experimental group), while the
      other 10 babies continued feeding with bottles by other manufacturers (the
      control group). A significant improvement was exhibited in the experimental group
      after 1 week of feeding with BornFree bottles, with a further significant
      improvement in the second week. Although they had different venting systems, the
      control group maintained the same level of colic symptoms as in the beginning of
      the study. We conclude that using BornFree baby bottles can effectively reduce
      colic symptoms in diagnosed babies.

PMID- 23549216
TI  - Self-care predictors for success post-bariatric surgery: a literature review.
AB  - The prevalence of obesity in the United States has more than doubled from 1980 to
      2008. Obesity leads to a multitude of comorbidities, most notably diabetes and
      cardiovascular diseases, resulting in more than $147 billion annually in
      healthcare costs. Bariatric surgery is becoming a common weight loss option for
      morbidly obese individuals. Studies in this review examine patients who have
      undergone laparoscopic adjustable gastric banding or Roux-en-Y gastric bypass
      surgery. Patients initially lose large amounts of weight postoperatively;
      unfortunately, around 30% of these individuals begin to regain weight 18-24
      months after surgery. The purpose of this article is to analyze the current
      literature to ascertain which self-care variables are predictors of successful
      long-term weight loss after bariatric surgery. The studies analyzed in this
      review found that patients who undergo a surgical weight loss intervention lose
      more weight faster than patients who do not have a surgical weight loss
      intervention. However, patients reported feeling unprepared for the extreme
      psychosocial and lifestyle changes after bariatric surgery. Findings from these
      studies point to the need for future research in the area of postsurgical
      psychosocial support for successful long-term weight loss maintenance.

PMID- 23549217
TI  - Wisdom: collective knowledge or innate?

PMID- 23549218
TI  - Rifaximin: a nonsystemic antibiotic for hepatic encephalopathy.

PMID- 23549219
TI  - Magnesium and parathyroid hormone levels of patients using different proton pump
      inhibitors: is there a real link?

PMID- 23549221
TI  - Investigation on the electronic structure of BN nanosheets synthesized via carbon
      substitution reaction: the arrangement of B, N, C and O atoms.
AB  - Graphene-like BN nanosheets were synthesized via carbon-substitution reaction
      using graphene as a template in an attempt to produce C-doped BN. The carbon
      residue was removed by high-temperature oxidation in air. The role of the
      graphene template and oxygen with regard to the local structure of BN and its
      defect-related optical luminescence are investigated using X-ray absorption near
      edge structure (XANES) and X-ray excited optical luminescence (XEOL). The
      structure and bonding of B, N, C and O in different chemical environments before
      and after oxidation are revealed by XANES. It is found that B and N atoms tend to
      form large BN domains, whereas the formation of B-C or N-C bonding is not
      significant. Two types of O local structures are found under different oxidation
      temperatures, as revealed by XANES: moderate oxidation results in O substituting
      N, while B2O3-like local structure is formed under higher oxidation temperature.
      The two types of O-related defects exhibit different luminescence properties.

PMID- 23549220
TI  - Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial
      communities at homeostasis.
AB  - Patients with inflammatory bowel diseases (IBD) harbour intestinal bacterial
      communities with altered composition compared with healthy counterparts; however,
      it is unknown whether changes in the microbiota are associated with genetic
      susceptibility of individuals for developing disease or instead reflect other
      changes in the intestinal environment related to the disease itself. Since
      deficiencies in the innate immune receptors Nod1 and Nod2 are linked to IBD, we
      tested the hypothesis that Nod-signaling alters intestinal immune profiles and
      subsequently alters bacterial community structure. We used qPCR to analyze
      expression patterns of selected immune mediators in the ileum and cecum of Nod
      deficient mice compared with their Nod-sufficient littermates and assessed the
      relative abundance of major bacterial groups sampled from the ileum, cecum and
      colon. The Nod1-deficient ileum exhibited significantly lower expression of Nod2,
      Muc2, alpha- and beta-defensins and keratinocyte-derived chemokine (KC),
      suggesting a weakened epithelial barrier compared with WT littermates; however,
      there were no significant differences in the relative abundance of targeted
      bacterial groups, indicating that Nod1-associated immune differences alone do not
      promote dysbiosis. Furthermore, Nod2-deficient mice did not display any changes
      in the expression of immune markers or bacterial communities. Shifts in bacterial
      communities that were observed in this study correlated with housing conditions
      and were independent of genotype. These findings emphasize the importance of
      using F2 littermate controls to minimize environmental sources of variation in
      microbial analyses, to establish baseline conditions for host-microbe homeostasis
      in Nod-deficient mice and to strengthen models for testing factors contributing
      to microbial dysbiosis associated with IBD.

PMID- 23549222
TI  - A simple method for in situ-labelling with 15N and 13C of grassland plant species
      by foliar brushing.
AB  - 1.Labelling plants with 15N and 13C stable isotopes usually require cultivation
      of plants in isotopically enriched soil and gas-tight labelling chambers - both
      approaches are not suitable if one aims to investigate in situ species
      interactions in real plant communities. 2.In this greenhouse experiment, we
      tested a labelling method in which dual-labelled (15N, 13C) urea solution is
      brushed directly onto leaves of twelve temperate grassland species representing
      grasses, non-leguminous forbs and legumes. 3.Across all plant species, shoots
      (15N: 0.145; 13C: 0.090 atom percent excess, APE) and roots (15N: 0.051; 13C:
      0.023 APE) were significantly enriched after five daily labelling events.
      Generally, isotopic enrichments were significantly higher in shoots than in
      roots. No clear pattern of absolute isotopic enrichment was observed between
      plant functional groups; however, grasses showed a more even allocation between
      shoots and roots than forbs and legumes. Isotopic enrichment levels after 4 weeks
      were lower, higher or unchanged compared to those of week one and varied between
      species or plant parts. 4.Considering the consistent enrichment levels and
      simplicity of this method, we conclude that it can be applied widely in
      ecological studies of above-belowground plant-plant or plant-animal interactions
      even in real plant communities.

PMID- 23549223
TI  - Complementary ligands direct the formation of a calix[8]arene-supported
      ferromagnetic Mn(IV)Mn(III) dimer.
AB  - A combination of complementary ligands, p-tert-butylcalix[8]arene (TBC[8]) and
      phenyl salicylaldoxime (Ph-saoH2) have been utilised in the facile synthesis of a
      Mn(III)Mn(IV) dimer. Magnetic measurements reveal ferromagnetic exchange between
      the two metal ions.

PMID- 23549224
TI  - In situ fluorescence and electrochemical monitoring of a photosynthetic microbial
      fuel cell.
AB  - Using an in-house developed platform, the performance of an Arthrospira maxima
      biofilm photosynthetic microbial fuel cell (PMFC) was monitored both optically
      and electrochemically. Fluorescence (excitation wavelength 633 nm, emission range
      640 to 800 nm for detection of fluorescence), power density and current output of
      the PMFC were recorded in real time. Confocal microscopy performed in situ
      allowed detailed fluorescence imaging to further improve the understanding of the
      photosynthetic activity of the biofilm that developed on the anode surface of the
      PMFC, whilst power and current outputs indicated the performance of the cell. The
      PMFC was shown to be sensitive to temperature and light perturbations with
      increased temperatures and light intensities resulting in improved performance. A
      direct relationship between the fluorescent signature and the amount of current
      produced was identified. With a decreasing external load and increasing current
      production, the biofilm attached to the anode electrode showed increased
      fluorescence inferring improved activity of the photosynthetic material.
      Furthermore, the imaging proved that viable cells covered the entire surface area
      of the biofilm and that the fluorescence increased with increasing distance (z
      axis) from the electrode surface.

PMID- 23549225
TI  - Prophylactic effects of duloxetine on post-stroke depression symptoms: an open
      single-blind trial.
AB  - Post-stroke depression (PSD) is a common yet severe sequela of stroke, and is
      often accompanied with somatic symptoms. Duloxetine, a new serotonin
      norepinephrine reuptake inhibitor, may help to prevent depression after stroke.
      95 ischemic stroke patients without depression were randomly divided into two
      groups: duloxetine group (n = 47) and control group (n = 48). Patients in the
      control group received routine ischemic stroke therapy, whereas patients in the
      duloxetine group received duloxetine (dose range 30-90 mg) for 12 weeks in
      addition to routine therapy. Follow-up observations lasted for 24 weeks. The
      Hamilton Depression Scale was used to measure depression, and the National
      Institute of Stroke Scale, Mini-Mental State Examination, Activities of Daily
      Living Scale (Chinese version) and Short Form 36 Health Survey Questionnaire were
      used to assess neurological function, cognitive function, rehabilitation from
      stroke and quality of life. Results showed that in general, duloxetine spared
      ischemic stroke patients from both minor and major depression by 16%. In
      addition, duloxetine helped patients to rehabilitate more rapidly from stroke,
      and was associated with better cognitive function and quality of life. In
      conclusion, the prophylactic use of duloxetine not only decreased the incidence
      of PSD, but also promoted rehabilitation, cognitive function and quality of life.

PMID- 23549226
TI  - "It helps me transform in my life from the past to the new": the meaning of
      resources for former child soldiers.
AB  - Although former child soldiers face considerable challenges after their return
      from the warring faction to the war-affected society, the presence of resources
      enables many to maintain well-being in the wake of child soldiering. Academic
      research has recently engaged with identifying these salient resources, but has
      left the question why they are helpful to former child soldiers largely
      unaddressed. This study therefore focuses on the meaning underlying certain
      phenomena that causes them to become resources. Semistructured in-depth
      interviews and a free-listing task on resources were conducted with 48 northern
      Ugandan former child soldiers. The phenomenological hermeneutical method is
      applied to analyze their lived experiences and the meaning they assign to
      resources. Four essential themes emerge from this study, representing the
      fourfold meaning of resources for former child soldiers in helping them (a) to
      break with their former existence as child soldiers, (b) to be able to overcome
      the challenges in their current life, (c) to belong to others and the environment
      to which they have returned, and (d) to become the person they aspire to be.
      Considering these research themes in the context of former child soldiers' return
      process, parallels with theories on transition are recognized and further
      explored so as to contextualize this emerging meaning. As such, this research
      delivers empirical evidence illustrating how resources help to pilot former child
      soldiers through transition in the wake of child soldiering. 

PMID- 23549227
TI  - Lack of genomic instability in bone marrow cells of SCID mice exposed whole-body
      to low-dose radiation.
AB  - It is clear that high-dose radiation is harmful. However, despite extensive
      research, assessment of potential health-risks associated with exposure to low
      dose radiation (at doses below or equal to 0.1 Gy) is still challenging.
      Recently, we reported that 0.05 Gy of 137Cs gamma rays (the existing limit for
      radiation-exposure in the workplace) was incapable of inducing significant in
      vivo genomic instability (measured by the presence of late-occurring chromosomal
      damage at 6 months post-irradiation) in bone marrow (BM) cells of two mouse
      strains, one with constitutively high and one with intermediate levels of the
      repair enzyme DNA-dependent protein-kinase catalytic-subunit (DNA-PKcs). In this
      study, we present evidence for a lack of genomic instability in BM cells of the
      severely combined-immunodeficiency (SCID/J) mouse (which has an extremely low
      level of DNA-PKcs activity) exposed whole-body to low-dose radiation (0.05 Gy).
      Together with our previous report, the data indicate that low-dose radiation
      (0.05 Gy) is incapable of inducing genomic instability in vivo (regardless of the
      levels of DNA-PKcs activity of the exposed mice), yet higher doses of radiation
      (0.1 and 1 Gy) do induce genomic instability in mice with intermediate and
      extremely low-levels of DNA-PKcs activity (indicating an important role of DNA
      PKcs in DNA repair).

PMID- 23549228
TI  - The contribution of neighbourhood material and social deprivation to survival: a
      22-year follow-up of more than 500,000 Canadians.
AB  - BACKGROUND: We examined the incremental influence on survival of neighbourhood
      material and social deprivation while accounting for individual level
      socioeconomic status in a large population-based cohort of Canadians. METHODS:
      More than 500,000 adults were followed for 22 years between 1982 and 2004. Tax
      records provided information on sex, income, marital status and postal code while
      a linkage was used to determine vital status. Cox models were used to estimate
      hazard ratios (HR) for quintiles of neighbourhood material and social
      deprivation. RESULTS: There were 180,000 deaths over the follow-up period. In
      unadjusted analyses, those living in the most materially deprived neighbourhoods
      had elevated risks of mortality (HR(males) 1.37, 95% CI: 1.33-1.41; HR(females)
      1.20, 95% CI: 1.16-1.24) when compared with those living in the least deprived
      neighbourhoods. Mortality risk was also elevated for those living in socially
      deprived neighbourhoods (HR(males) 1.15, CI: 1.12-1.18; HR(females) 1.15, CI:
      1.12-1.19). Mortality risk associated with material deprivation remained elevated
      in models that adjusted for individual factors (HR(males) 1.20, CI: 1.17-1.24;
      HR(females) 1.16, CI: 1.13-1.20) and this was also the case for social
      deprivation (HR(males) 1.12, CI: 1.09-1.15; HR(females) 1.09, CI: 1.05-1.12).
      Immigrant neighbourhoods were protective of mortality risk for both sexes. Being
      poor and living in the most socially advantageous neighbourhoods translated into
      a survival gap of 10% over those in the most socially deprived neighbourhoods.
      The gap for material neighbourhood deprivation was 7%. CONCLUSIONS: Living in
      socially and materially deprived Canadian neighbourhoods was associated with
      elevated mortality risk while we noted a "healthy immigrant neighbourhood
      effect". For those with low family incomes, living in socially and materially
      deprived areas negatively affected survival beyond their individual
      circumstances.

PMID- 23549229
TI  - Bioaccumulation of trace elements in Ruditapes philippinarum from China: public
      health risk assessment implications.
AB  - The Manila clam Ruditapes philippinarum is one of the most important commercial
      bivalve species consumed in China. Evaluated metal burden in bivalve molluscs can
      pose potential risks to public health as a result of their frequent consumption.
      In this study, concentrations of 10 trace elements (Cu, Zn, Mn, Se, Ni, Cd, Cr,
      Pb, Hg and As) were determined in samples of the bivalve Ruditapes philippinarum,
      collected from nine mariculture zones along the coast of China between November
      and December in 2010, in order to evaluate the status of elemental metal
      pollution in these areas. Also, a public health risk assessment was untaken to
      assess the potential risks associated with the consumption of clams. The ranges
      of concentrations found for Cu, Zn, Mn, Se, Ni, Cd, Cr, Pb, Hg and As in R.
      philippinarum were 12.1-38.0, 49.5-168.3, 42.0-68.0, 4.19-8.71, 4.76-14.32, 0.41
      1.11, 0.94-4.74, 0.32-2.59, 0.03-0.23 and 0.46-11.95 mg.kg(-1) dry weight,
      respectively. Clear spatial variations were found for Cu, Zn, Cr, Pb, Hg and As,
      whereas Mn, Se, Ni, and Cd did not show significant spatial variation. Hotspots
      of trace element contamination in R. philippinarum can be found along the coast
      of China, from the north to the south, especially in the Bohai and Yellow Seas.
      Based on a 58.1 kg individual consuming 29 g of bivalve molluscs per day, the
      values of the estimated daily intake (EDI) of trace elements analyzed were
      significantly lower than the values of the accepted daily intake (ADI)
      established by Joint Food and Agriculture Organization/World Health Organization
      Expert Committee on Food Additives (JFAO/WHO) and the guidelines of the reference
      does (RfD) established by the United States Environmental Protection Agency
      (USEPA). Additionally, the risk of trace elements to humans through R.
      philippinarum consumption was also assessed. The calculated hazard quotients (HQ)
      of all trace elements were less than 1. Consequently, there was no obvious public
      risk from the intake of these trace elements through R. philippinarum
      consumption.

PMID- 23549230
TI  - Noninvasive imaging of myocardial extracellular matrix for assessment of
      fibrosis.
AB  - PURPOSE OF REVIEW: Myocardial fibrosis is a common feature of many
      cardiomyopathies, including hypertrophic cardiomyopathy. Myocardial fibrosis has
      been shown to be reversible and treatable with timely intervention. Although
      early detection and assessment of fibrosis is crucial, adequate diagnostics are
      still in development. Recent studies have shown progress on noninvasive imaging
      methods of fibrosis using cardiovascular magnetic resonance (CMR) and nuclear
      imaging modalities. RECENT FINDINGS: T1 mapping and extracellular volume mapping
      (ECV) combined with CMR imaging are cutting edge methods that have the potential
      to assess interstitial myocardial fibrosis. Recent findings show that ECV
      measurement can be correlated to the extent of diffuse fibrosis. Comparatively,
      molecular imaging targets specific biomarkers in the fibrosis formation pathway
      and provides enhanced sensitivity for imaging early disease. Biomarkers include
      molecules involved in angiogenesis, ventricular remodeling, and fibrotic tissue
      formation, whereas collagen targeted agents can directly identify fibrotic tissue
      in the heart. SUMMARY: This review introduces novel methods of fibrosis imaging
      that utilize properties of extracellular matrix and its biomarkers. Changes in
      characteristics and cellular biomarkers of the extracellular space can provide
      significant information regarding fibrosis formation and its role in
      cardiomyopathy. Ultimately, these findings may improve detection and monitoring
      of disease and improve efficiency and effectiveness of the treatment.

PMID- 23549231
TI  - Atrial fibrillation and heart failure: beyond the heart rate.
AB  - PURPOSE OF REVIEW: Atrial fibrillation and heart failure are two of the most
      prevalent cardiovascular disease conditions. They often coexist and lead to
      significant morbidity and mortality. Adequate management strategies for this dual
      epidemic continue to be the subject of many research studies. RECENT FINDINGS:
      Recent clinical trials suggest that a rhythm control strategy for atrial
      fibrillation does not offer a survival advantage over rate control in heart
      failure patients with reduced systolic function. Rhythm control in these trials
      was achieved using antiarrhythmic drugs, with evidence of increased mortality
      associated with certain agents. Catheter ablation is a more effective and
      increasingly used approach to maintain sinus rhythm in atrial fibrillation
      patients, with promising results in the heart failure population. Late-gadolinium
      enhancement cardiac MRI (LGE-MRI) assessment of atrial fibrosis helps in
      selecting the better candidates for atrial fibrillation ablation. AV nodal
      ablation and bi-ventricular pacing remains another viable option. Atrial
      fibrillation patients with heart failure and preserved systolic function are
      another group in whom maintenance of sinus rhythm is thought to be advantageous.
      SUMMARY: Patients with atrial fibrillation and heart failure are a heterogeneous
      group and require a personalized treatment approach. Catheter ablation to restore
      and maintain sinus rhythm is a modality that promises to be advantageous beyond
      rate control.

PMID- 23549232
TI  - Management of ventricular arrhythmias in patients with ventricular assist
      devices.
AB  - PURPOSE OF REVIEW: To summarize the available evidence concerning the occurrence
      and treatment of ventricular arrhythmias in patients supported with long-term
      ventricular assist devices (VADs). RECENT FINDINGS: Approximately one-third of
      left ventricular assist device-supported patients experience significant
      ventricular arrhythmias, with higher rates in certain patient subsets.
      Ventricular arrhythmias are associated with both increased mortality and
      morbidity in VAD-supported patients. Mechanical factors, myocardial fibrosis and
      alterations in cardiac myocyte physiology because of myocardial unloading are
      contributors to ventricular arrhythmias in this population. In the absence of
      definitive trials, current evidence supports implanted cardioverter
      defibrillators (ICDs) in long-term VAD patients to mitigate the risks associated
      with ventricular arrhythmias. Though antiarrhythmic therapies have limited
      efficacy, amelioration of inflow cannula contact with the endocardium and suction
      events or ablation of specific anatomic origins of ventricular arrhythmias, when
      present, are also efficacious in VAD-supported hearts. SUMMARY: As the
      application of long-term VAD support continues to grow, it will be increasingly
      important to clarify and target the mechanisms contributing to ventricular
      arrhythmias in this population. Prospective trials assessing the benefits of de
      novo ICD placement, ablative strategies and other prophylactic and therapeutic
      interventions will be increasingly important to further improve the survival and
      quality of life among VAD-supported patients.

PMID- 23549233
TI  - Genetics and sudden death.
AB  - PURPOSE OF REVIEW: Sudden cardiac death (SCD) affects a significant percentage of
      young individuals. SCDs are due to genetic heart disorders, such as
      cardiomyopathies and channelopathies. In the present review, we will describe the
      recent advancements in understanding the genetic and molecular basis of
      hereditary cardiac diseases. RECENT FINDINGS: Considerable progress has been made
      in identification of new genes associated with monogenic familial arrhythmogenic
      syndromes, giving the opportunity to delineate their molecular pathogenesis and
      identify potential targets for therapeutic intervention. Research discoveries and
      rapidly dropping costs of DNA sequencing technologies have resulted in
      availability of genetic testing panels. SUMMARY: Advances in genetic sequencing
      technology are expected to significantly impact the clinical practice in the near
      future. Genetic testing represents a powerful tool for cause determination of
      arrhythmogenic cardiac diseases, efficient screening of family members, possible
      risk stratification and treatment choices. However, specific expertise is
      required for rational ordering and correct interpretation of the genetic
      screening results.

PMID- 23549234
TI  - Errors in DNA replication and genetic diseases.

PMID- 23549235
TI  - Heart rate and heart failure: the role of ivabradine therapy.
AB  - PURPOSE OF REVIEW: The clinical data about the impact of heart rate reduction in
      heart failure therapy will be reviewed. RECENT FINDINGS: Clinical and
      experimental studies showed an association between elevated resting heart rate
      and mortality risk in heart failure patients. This review summarizes that heart
      rate level at rest and its extent of reduction is a sensitive indicator for
      outcome in heart failure. In addition to the nonspecific heart rate reducing
      drugs like beta-blockers, cardiac glycosides and Ca(2+) antagonists, ivabradine
      is a highly selective heart rate reducing agent without modifying ventricular
      contractility and atrioventricular conduction in humans and animals, and has
      recently been shown to improve cardiovascular outcomes in patients with systolic
      heart failure by lowering the heart rate only. The present and future role of
      heart rate reduction in the spectrum of heart failure disease and therapy will be
      outlined and evaluated. SUMMARY: Elevated heart rate at rest represents a key
      indicator of adverse outcome in heart failure and implies a major treatment
      target in these patients.

PMID- 23549236
TI  - Approach to reduction of ventricular arrhythmias and implantable cardioverter
      defibrillator therapies in patients with heart failure.
AB  - PURPOSE OF REVIEW: Prevention of ventricular arrhythmias and implantable
      cardioverter-defibrillator (ICD) therapies in patients with heart failure will be
      reviewed. RECENT FINDINGS: ICD utilization in patients with heart failure has
      resulted in significantly improved long-term survival. However, there is growing
      evidence that ICD shocks are associated with increased morbidity and mortality.
      As a result, there is increasing emphasis on the treatment strategies to avoid
      ICD therapies. Optimal heart failure management with medical as well as cardiac
      resynchronization therapy when indicated is an essential part of treatment;
      however, adjunctive measures may be necessary to suppress ventricular
      arrhythmias, prevent unnecessary shocks, and improve quality of life. SUMMARY:
      Device programming can help avoid ICD therapies by delaying time to detection,
      increasing detection rate cutoffs, and discriminating between supraventricular
      and ventricular arrhythmias. Still, as patients live longer with advanced stages
      of heart failure, there will be a need to suppress sustained ventricular
      arrhythmias that would otherwise require ICD therapy. Antiarrhythmic drugs offer
      a noninvasive option to help suppress ventricular arrhythmias. With more
      experience and better catheter mapping and ablation techniques, there is a
      movement toward an early invasive strategy for ventricular tachycardia management
      in patients with heart failure.

PMID- 23549237
TI  - Catheter ablation of ventricular arrhythmias: targets, tactics, and tools.
AB  - PURPOSE OF REVIEW: Drug-refractory ventricular tachycardia in the setting of
      structural heart disease results in frequent implantable cardioverter
      defibrillator therapies and an increased risk of heart failure. Management
      requires catheter ablation procedures for effective suppression of the
      arrhythmia. RECENT FINDINGS: Imaging and electroanatomic mapping technologies
      provide new insights into the myocardial structural abnormalities responsible for
      ventricular tachycardia. Integration of imaging data with three-dimensional
      mapping systems coupled with improved targeting of abnormal electrical signals
      may improve the ablation outcomes. New ablation tools show promise for the
      effective ablation of previously unreachable myocardial ventricular tachycardia
      circuits. SUMMARY: Catheter ablation procedures have evolved over the last 2
      decades. Improved technology may contribute to more widespread utilization of
      catheter ablation in the future.

PMID- 23549238
TI  - Arrhythmias in heart failure: beyond sudden cardiac death.

PMID- 23549239
TI  - The role of clopidogrel in the management of ischemic heart disease.
AB  - PURPOSE OF REVIEW: Placebo-controlled randomized trials have demonstrated the
      efficacy of clopidogrel in combination with aspirin across a broad range of
      clinical presentations. Recent trials have addressed several remaining issues
      regarding clopidogrel therapy. RECENT FINDINGS: Three randomized trials examined
      the role of platelet function testing (PFT) in clopidogrel-treated patients. The
      results do not support the use of PFT to adjust clopidogrel dose after
      percutaneous coronary intervention (PCI), particularly in patients with stable
      angina or ischemia, in whom event rates are low irrespective of on-treatment
      reactivity. Doses greater than clopidogrel 150  mg daily are required to
      sufficiently overcome high reactivity in CYP2C19 loss-of-function (LOF) allele
      carriers. Clopidogrel response variability also influences the time to platelet
      recovery after drug discontinuation, and a proof-of-principle study supports the
      concept of using PFT for surgical timing. Unlike its efficacy in the setting of
      acute coronary syndrome (ACS) and PCI, prasugrel was not superior to clopidogrel
      in medically treated patients recovering from ACS. SUMMARY: Current data do not
      support routine PFT to guide antiplatelet therapy in patients undergoing
      nonurgent PCI. The role of PFT to optimize therapy in ACS patients remains
      unaddressed, and further study is needed to confirm its promise in guiding
      surgical timing in patients who have discontinued therapy. Clopidogrel remains an
      important therapeutic option for patients presenting after an ACS who did not
      undergo initial revascularization.

PMID- 23549240
TI  - Nutraceuticals and coronary heart disease.
AB  - PURPOSE OF REVIEW: Although many reviews have focused on diet as a determinant of
      coronary heart disease (CHD), little is known about the use of specific nutrients
      or food products. The aim of this review was to examine the role of several
      functional foods, or nutraceuticals, in the prevention or treatment of CHD.
      RECENT FINDINGS: CHD continues to be one of the main causes of death in modern
      societies. Far from diminishing, its prevalence and incidence continue to grow
      and are probably linked to the increase in metabolic disorders such as obesity,
      diabetes and metabolic syndrome. Numerous preventive measures and treatments are
      being considered for these metabolic diseases. In this context, nutraceuticals
      and functional foods are seen as powerful tools for maintaining health and
      fighting against cardiometabolic risk factors. For example, the association
      between saturated fat and the development of CHD has been clearly established.
      However, the consumption of other sources of fat, such as olive oil enriched in
      monounsaturated fatty acids, has been associated with beneficial cardiovascular
      effects. SUMMARY: Nutraceuticals have demonstrated physiological effects that
      have a positive influence on the development of atherosclerosis and therefore of
      CHD.

PMID- 23549242
TI  - In vitro skin permeation and penetration of nonivamide from novel film-forming
      emulsions.
AB  - The purpose of this study was to develop film-forming emulsions (FFE)
      facilitating long-term treatment of chronic pruritus with capsaicinoids. To this
      end, oil-in-water emulsions, which comprise dispersions of sustained-release
      polymers, were examined. Such emulsions form a film when applied to the skin and
      encapsulate the oily drug solution in a dry polymeric matrix. Permeation of the
      antipruritic drug nonivamide (NVA) is controlled by the matrix. Permeation rates
      of NVA from FFE and its concentration in the skin are equivalent to those
      achieved with a conventional semisolid formulation, but can be maintained for a
      longer period of time. FFE may therefore improve the treatment of chronic
      pruritus with capsaicinoids by enhancing patient compliance by means of a
      sustained-release regimen. 

PMID- 23549244
TI  - Analysis of 85Kr: a comparison at the 10 -14 level using micro-liter samples.
AB  - The isotopic abundance of (85)Kr in the atmosphere, currently at the level of 10(
      11), has increased by orders of magnitude since the dawn of nuclear age. With a
      half-life of 10.76 years, (85)Kr is of great interest as tracers for
      environmental samples such as air, groundwater and ice. Atom Trap Trace Analysis
      (ATTA) is an emerging method for the analysis of rare krypton isotopes at
      isotopic abundance levels as low as 10(-14) using krypton gas samples of a few
      micro-liters. Both the reliability and reproducibility of the method are examined
      in the present study by an inter-comparison among different instruments. The
      (85)Kr/Kr ratios of 12 samples, in the range of 10(-13) to 10(-10), are measured
      independently in three laboratories: a low-level counting laboratory in Bern,
      Switzerland, and two ATTA laboratories, one in Hefei, China, and another in
      Argonne, USA. The results are in agreement at the precision level of 5%.

PMID- 23549245
TI  - Family psychological stress early in life and development of type 1 diabetes: the
      ABIS prospective study.
AB  - AIMS: This study investigated whether psychological stress in the family during
      the child's first year of life are associated with the risk of childhood type 1
      diabetes (T1D). According to the beta-cell stress hypothesis all factors that
      increase the need for, or the resistance to, insulin may be regarded as risk
      factors for T1D. METHODS: Among 8921 children from the general population with
      questionnaire data from one parent at child's birth and at 1 year of age, 42
      cases of T1D were identified up to 11-13 years of age. Additionally 15 cases with
      multiple diabetes-related autoantibodies were detected in a sub-sample of 2649
      children. RESULTS: Cox regression analyses showed no significant associations
      between serious life events (hazard ratio 0.7 for yes vs. no [95% CI 0.2-1.9],
      p=0.47), parenting stress (0.9 per scale score [0.5-1.7], p=0.79), or parental
      dissatisfaction (0.6 per scale score [0.3-1.2], p=0.13) during the first year of
      life and later diagnosis of T1D, after controlling for socioeconomic,
      demographic, and diabetes-related factors. Inclusion of children with multiple
      autoantibodies did not alter the results. CONCLUSIONS: No association between
      psychological stress early in life and development of T1D could be confirmed.

PMID- 23549246
TI  - Elevated serum beta2-glycoprotein-I-lipoprotein(a) complexes levels are
      associated with the presence and complications in type 2 diabetes mellitus.
AB  - AIMS: To examine the serum levels of beta2-glycoprotein I-lipoprotein(a)
      complexes [beta2-GPI-Lp(a)] in type 2 diabetes mellitus (T2DM) patients and
      evaluate the association of the complexes with complications in T2DM. METHODS:
      Fifty two T2DM patients (22 with complications and 30 free of complications) and
      52 age/gender-matched healthy controls were studied. Serum concentrations of
      beta2-GPI-Lp(a) and ox-Lp(a) were measured by "sandwich" ELISAs and their
      associations with complications were examined using multiple linear regression.
      RESULTS: Mean serum beta2-GPI-Lp(a) (1.19 +/- 0.30 U/mL vs. 0.89 +/- 0.20 U/mL,
      p<0.001) and ox-Lp(a) concentrations (13.34 +/- 11.73 mg/L vs. 5.26 +/- 3.34
      mg/L, p<0.001) were both significantly higher in T2DM than in controls. The area
      under the ROC curve (AUC) for beta2-GPI-Lp(a) and ox-Lp(a) was 0.725 and 0.738,
      respectively. beta2-GPI-Lp(a) levels were markedly higher in patients with
      complications than those without complication (1.39 +/- 0.28 U/mL vs. 1.04 +/-
      0.31 U/mL, p<0.01), whereas no marked difference was found in ox-Lp(a). In
      multivariate regression analysis, the association between beta2-GPI-Lp(a) and
      complications remained significant (beta=0.249, p<0.05, respectively) after
      adjustments were made for other traits. CONCLUSIONS: Elevated beta2-GPI-Lp(a) may
      reflect chronic underlying pathophysiological processes involved in development
      of complications of T2DM.

PMID- 23549247
TI  - We need your input ... this is your opportunity to have a voice in the future of
      your profession.

PMID- 23549248
TI  - Nursing home, assisted living, and other extended care costs continue to rise in
      the United States: annual market survey from the MetLife Mature Market Institute
      contains costs in each state.

PMID- 23549249
TI  - Evidence-based practice in hospice: is qualitative more appropriate than
      quantitative?
AB  - Evidence-based practice has become the accepted phrase relative to healthcare
      quality and outcomes. Hospice providers have begun to express an interest in
      applying evidence to practice. Evidence-based practice, with its tiers of
      evidence, ranks quantitative research methods at the top. However, there is
      concern that applying evidence-based practice to a subjective concept like pain
      and suffering may be problematic. A more balanced approach to quality outcomes in
      hospice care may need to involve patient experience and qualitative research.

PMID- 23549250
TI  - Parenteral inotropic therapy in the home: an update for home care and hospice.
AB  - This article provides an evidence-based overview of heart failure (HF), including
      its pathogenesis, staging, assessment, prognosis, and treatment with intravenous
      inotropic medications in the home. Inotropic infusions in the home setting
      require advanced care planning, symptom management, and knowledge about
      ambulatory pumps and devices. These medications can be safely used throughout the
      continuum of care as pediatric/adult bridges from transplant to hospice care.
      Nurses who recognize advanced HF symptomatology and use prognostic/risk
      stratification models will be better prepared to facilitate this advanced care
      planning, thus supporting optimal treatment outcomes. The ultimate goal of care
      for heart failure therapy in the home is to integrate pharmacotherapeutic
      knowledge of treatment advances with comfort measures and to provide them to
      patients concurrently and in a seamless process.

PMID- 23549252
TI  - Evidence about the pharmacological management of constipation, part 2:
      implications for palliative care.
AB  - Constipation remains a challenging problem for patients and caregivers in home
      healthcare. Part 1 of this two-part series discussed the scope, physiology, and
      evidence-based practice for nonpharmacological interventions for constipation.
      This second article will focus on evidence-based pharmacological prevention and
      management of constipation, medication cost, and implications for palliative
      care.

PMID- 23549255
TI  - Rural healthcare and the challenges of home healthcare and hospice.

PMID- 23549256
TI  - A personal perspective on death and dying.

PMID- 23549257
TI  - Green scalable aerosol synthesis of porous metal-organic frameworks.
AB  - Benchmarked micro or nanosized HKUST-1, ZIF-8 and Fe3(BTC)2 as well as template
      assisted Fe3(BTC)2 metal-organic frameworks (MOFs) of various morphologies were
      synthesized via a green and scalable aerosol route. Their high space time yields
      make this continuous method very promising for the industrial production and
      shaping of MOFs.

PMID- 23549258
TI  - The undefined role of Gram positive bacteria in chronic prostatitis development.

PMID- 23549259
TI  - Complementary mechanistic properties of Fe- and Mn-doped aluminophosphates in the
      catalytic aerobic oxidation of hydrocarbons.
AB  - A comparative computational study of the reaction mechanisms for hydrocarbon
      oxidations catalysed by Mn- and Fe-doped nanoporous aluminophosphates shows
      distinctive features for each transition metal depending on its electronic
      configuration. Preactivation of Mn catalysts is easier due to the higher
      stability of Mn(II), but its oxidation during propagation requires activation
      barriers. In contrast, preactivation of Fe is more difficult and avoids a direct
      Fe reduction because of the low stability of Fe(II). Fe(II) is only produced at
      the end of the propagation cycle, favoured by an energetic compensation caused by
      the simultaneous exothermic oxidation of an alcohol molecule. Fe-catalysed
      propagation is kinetically favoured since it requires lower activation barriers,
      and is further assisted by higher adsorption energies of the reactants and lower
      desorption energies of the products on the active site. The mechanistic
      information gained can be used for the rational design of improved oxidation
      catalysts.

PMID- 23549260
TI  - Tacrolimus monotherapy: a promising option for ocular myasthenia gravis.

PMID- 23549261
TI  - The competition between template growth and catalytic growth of one-dimensional
      ZnS nanostructures: nanobelts or nanowires.
AB  - Template growth and catalytic growth are two typical mechanisms for the solution
      chemistry synthesis of one-dimensional (1D) II-VI semiconductor nanomaterials.
      Here, we systematically demonstrate the competition relationship between them by
      tuning the synthesis of 1D ZnS nanostructures in different chain-length primary
      alkyl-amines. The template growth, derived from the coordination effect of
      amines, produces ZnS nanobelts and will compete with the Ag2S-catalyzed mechanism
      as AgNO3 is added into these amines. In short-chain n-propylamine and n
      butylamine the template growth is much stronger than the catalytic growth,
      leading to the morphology maintenance of ZnS nanobelts, whereas the latter
      replaces the former in long-chain n-octylamine and n-dodecylamine due to the
      decrease of coordination ability of amines, which yields ZnS nanowires instead of
      nanobelts. A balance of competition is built between these two mechanisms in
      middle-length n-hexylamine, producing a mixture of ZnS nanobelts and nanowires.
      The morphology and growth mechanism changes of ZnS nanostructures have been
      rationally investigated using various characterization techniques. Meanwhile, the
      optical properties of the products synthesized before and after adding AgNO3 are
      comparatively studied by UV-vis absorption and photoluminescence (PL) spectra.

PMID- 23549262
TI  - Distinct signaling cascades elicited by different formyl peptide receptor 2
      (FPR2) agonists.
AB  - The formyl peptide receptor 2 (FPR2) is a remarkably versatile transmembrane
      protein belonging to the G-protein coupled receptor (GPCR) family. FPR2 is
      activated by an array of ligands, which include structurally unrelated lipids and
      peptide/proteins agonists, resulting in different intracellular responses in a
      ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4,
      several other endogenous agonists also bind FPR2, including serum amyloid A,
      glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the
      activation of FPR2 may result in potent pro- or anti-inflammatory responses.
      Other endogenous ligands, also present in biological samples, include resolvins,
      amyloidogenic proteins, such as beta amyloid (Abeta)-42 and prion protein
      (Prp)106-126, the neuroprotective peptide, humanin, antibacterial peptides,
      annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive
      intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide
      (PACAP)-27, and mitochondrial peptides. Upon activation, intracellular domains of
      FPR2 mediate signaling to G-proteins, which trigger several agonist-dependent
      signal transduction pathways, including activation of phospholipase C (PLC),
      protein kinase C (PKC) isoforms, the phosphoinositide 3-kinase (PI3K)/protein
      kinase B (Akt) pathway, the mitogen-activated protein kinase (MAPK) pathway,
      p38MAPK, as well as the phosphorylation of cytosolic tyrosine kinases, tyrosine
      kinase receptor transactivation, phosphorylation and nuclear translocation of
      regulatory transcriptional factors, release of calcium and production of
      oxidants. FPR2 is an attractive therapeutic target, because of its involvement in
      a range of normal physiological processes and pathological diseases. Here, we
      review and discuss the most significant findings on the intracellular pathways
      and on the cross-communication between FPR2 and tyrosine kinase receptors
      triggered by different FPR2 agonists.

PMID- 23549264
TI  - Digoxin downregulates NDRG1 and VEGF through the inhibition of HIF-1alpha under
      hypoxic conditions in human lung adenocarcinoma A549 cells.
AB  - Digoxin, an inhibitor of Na+/K+ ATPase, has been used in the treatment of heart
      related diseases (such as congestive heart failure and atrial arrhythmia) for
      decades. Recently, it was reported that digoxin is also an effective HIF-1alpha
      inhibitor. We investigated whether digoxin could suppress tumor cell growth
      through HIF-1alpha in non-small cell lung cancer cells (A549 cells) under hypoxic
      conditions. An MTT assay was used to measure cell viability. RT-PCR and western
      blotting were performed to analyze the mRNA and protein expression of VEGF,
      NDRG1, and HIF-1alpha. HIF-1alpha nuclear translocation was then determined by
      EMSA. Digoxin was found to inhibit the proliferation of A549 cells under hypoxic
      conditions. Our results showed that hypoxia led to the upregulation of VEGF,
      NDRG1, and HIF-1alpha both at the mRNA and protein levels. We also found that the
      hypoxia-induced overexpression of VEGF, NDRG1, and HIF-1alpha was suppressed by
      digoxin in a concentration-dependent manner. As expected, our EMSA results
      demonstrated that under hypoxic conditions HIF-1alpha nuclear translocation was
      also markedly reduced by digoxin in a concentration-dependent manner. Our results
      suggest that digoxin downregulated hypoxia-induced overexpression of VEGF and
      NDRG1 at the transcriptional level probably through the inhibition of HIF-1alpha
      synthesis in A549 cells.

PMID- 23549265
TI  - Kinetic studies that evaluate the solvolytic mechanisms of allyl and vinyl
      chloroformate esters.
AB  - At 25.0  degrees C the specific rates of solvolysis for allyl and vinyl
      chloroformates have been determined in a wide mix of pure and aqueous organic
      mixtures. In all the solvents studied, vinyl chloroformate was found to react
      significantly faster than allyl chloroformate. Multiple correlation analyses of
      these rates are completed using the extended (two-term) Grunwald-Winstein
      equation with incorporation of literature values for solvent nucleophilicity (NT)
      and solvent ionizing power (YCl). Both substrates were found to solvolyze by
      similar dual bimolecular carbonyl-addition and unimolecular ionization channels,
      each heavily dependent upon the solvents nucleophilicity and ionizing ability.

PMID- 23549263
TI  - Peripheral reproductive organ health and melatonin: ready for prime time.
AB  - Melatonin has a wide variety of beneficial actions at the level of the gonads and
      their adnexa. Some actions are mediated via its classic membrane melatonin
      receptors while others seem to be receptor-independent. This review summarizes
      many of the published reports which confirm that melatonin, which is produced in
      the ovary, aids in advancing follicular maturation and preserving the integrity
      of the ovum prior to and at the time of ovulation. Likewise, when ova are
      collected for in vitro fertilization-embryo transfer, treating them with
      melatonin improves implantation and pregnancy rates. Melatonin synthesis as well
      as its receptors have also been identified in the placenta. In this organ,
      melatonin seems to be of particular importance for the maintenance of the optimal
      turnover of cells in the villous trophoblast via its ability to regulate
      apoptosis. For male gametes, melatonin has also proven useful in protecting them
      from oxidative damage and preserving their viability. Incubation of ejaculated
      animal sperm improves their motility and prolongs their viability. For human
      sperm as well, melatonin is also a valuable agent for protecting them from free
      radical damage. In general, the direct actions of melatonin on the gonads and
      adnexa of mammals indicate it is an important agent for maintaining optimal
      reproductive physiology.

PMID- 23549267
TI  - A role for protein phosphatase 2A in regulating p38 mitogen activated protein
      kinase activation and tumor necrosis factor-alpha expression during influenza
      virus infection.
AB  - Influenza viruses of avian origin continue to pose pandemic threats to human
      health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated
      cytokine levels when compared with the seasonal H1N1 virus. We previously showed
      that H5N1/97 hyperinduces tumor necrosis factor (TNF)-alpha through p38 mitogen
      activated protein kinase (MAPK). However, the detailed mechanisms of p38MAPK
      activation and TNF-alpha hyperinduction following influenza virus infections are
      not known. Negative feedback regulations of cytokine expression play important
      roles in avoiding overwhelming production of proinflammatory cytokines. Here we
      hypothesize that protein phosphatases are involved in the regulation of cytokine
      expressions during influenza virus infection. We investigated the roles of
      protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase
      type 2A (PP2A) in modulating p38MAPK activation and downstream TNF-alpha
      expressions in primary human monocyte-derived macrophages (PBMac) infected with
      H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated
      p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1
      virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A
      inhibitor, p38MAPK phosphorylation and TNF-alpha production were further
      increased in the virus-infected macrophages. However, H9N2/G1 did not induce the
      expression of PP2A indicating that the activation of PP2A is not mediated by
      p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets
      of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced
      PP2A activation in primary macrophages. Our results may provide new insights into
      the control of cytokine dysregulation.

PMID- 23549268
TI  - Magnetic drug targeting reduces the chemotherapeutic burden on circulating
      leukocytes.
AB  - Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells
      during treatment with cytotoxic drugs. An anticancer drug is bound to
      superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular
      supply of the tumor and directed into the tumor by means of an external magnetic
      field. In this study, we investigated the impact of SPION, mitoxantrone (MTO) and
      SPIONMTO on cell viability in vitro and the nonspecific uptake of MTO into
      circulating leukocytes in vivo. MDT was compared with conventional chemotherapy.
      MTO uptake and the impact on cell viability were assessed by flow cytometry in a
      Jurkat cell culture. In order to analyze MTO loading of circulating leukocytes in
      vivo, we treated tumor-bearing rabbits with MDT and conventional chemotherapy. In
      vitro experiments showed a dose-dependent MTO uptake and reduction in the
      viability and proliferation of Jurkat cells. MTO and SPIONMTO showed similar
      cytotoxic activity. Non-loaded SPION did not have any effect on cell viability in
      the concentrations tested. Compared with systemic administration in vivo, MDT
      employing SPIONMTO significantly decreased the chemotherapeutic load in
      circulating leukocytes. We demonstrated that MDT spares the immune system in
      comparison with conventional chemotherapy.

PMID- 23549266
TI  - Plant nucleotide binding site-leucine-rich repeat (NBS-LRR) genes: active
      guardians in host defense responses.
AB  - The most represented group of resistance genes are those of the nucleotide
      binding site-leucine-rich repeat (NBS-LRR) class. These genes are very numerous
      in the plant genome, and they often occur in clusters at specific loci following
      gene duplication and amplification events. To date, hundreds of resistance genes
      and relatively few quantitative trait loci for plant resistance to pathogens have
      been mapped in different species, with some also cloned. When these NBS-LRR genes
      have been physically or genetically mapped, many cases have shown co-localization
      between resistance loci and NBS-LRR genes. This has allowed the identification of
      candidate genes for resistance, and the development of molecular markers linked
      to R genes. This review is focused on recent genomics studies that have described
      the abundance, distribution and evolution of NBS-LRR genes in plant genomes.
      Furthermore, in terms of their expression, NBS-LRR genes are under fine
      regulation by cis- and trans-acting elements. Recent findings have provided
      insights into the roles of alternative splicing, the ubiquitin/ proteasome
      system, and miRNAs and secondary siRNAs in the regulation of NBS-LRR gene
      expression at the post-transcriptional, post-translational and epigenetic levels.
      The possibility to use this knowledge for genetic improvement of plant resistance
      to pathogens is discussed.

PMID- 23549269
TI  - Water soluble usnic acid-polyacrylamide complexes with enhanced antimicrobial
      activity against Staphylococcus epidermidis.
AB  - Usnic acid, a potent antimicrobial and anticancer agent, poorly soluble in water,
      was complexed to novel antimicrobial polyacrylamides by establishment of strong
      acidic-base interactions. Thermal and spectroscopic analysis evidenced a
      molecular dispersion of the drug in the polymers and a complete drug/polymer
      miscibility for all the tested compositions. The polymer/drug complexes promptly
      dissolved in water and possessed a greater antimicrobial activity against
      Staphylococcus epidermidis than both the free drug and the polymer alone. The
      best results were obtained with the complex based on the lowest molecular weight
      polymer and containing a low drug content. Such a complex showed a larger
      inhibition zone of bacterial growth and a lower minimum inhibitory concentration
      (MIC) with respect to usnic acid alone. This improved killing effect is
      presumably due to the reduced size of the complexes that allows an efficient
      cellular uptake of the antimicrobial complexes. The killing effect extent seems
      to be not significantly dependent on usnic acid content in the samples.

PMID- 23549270
TI  - The critical role of potassium in plant stress response.
AB  - Agricultural production continues to be constrained by a number of biotic and
      abiotic factors that can reduce crop yield quantity and quality. Potassium (K) is
      an essential nutrient that affects most of the biochemical and physiological
      processes that influence plant growth and metabolism. It also contributes to the
      survival of plants exposed to various biotic and abiotic stresses. The following
      review focuses on the emerging role of K in defending against a number of biotic
      and abiotic stresses, including diseases, pests, drought, salinity, cold and
      frost and waterlogging. The availability of K and its effects on plant growth,
      anatomy, morphology and plant metabolism are discussed. The physiological and
      molecular mechanisms of K function in plant stress resistance are reviewed. This
      article also evaluates the potential for improving plant stress resistance by
      modifying K fertilizer inputs and highlights the future needs for research about
      the role of K in agriculture.

PMID- 23549271
TI  - Fabrication of magnetic-antimicrobial-fluorescent multifunctional hybrid
      microspheres and their properties.
AB  - Novel magnetic-antimicrobial-fluorescent multifunctional hybrid microspheres with
      well-defined nanostructure were synthesized by the aid of a poly(glycidyl
      methacrylate) (PGMA) template. The hybrid microspheres were fully characterized
      by scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      Fourier transform infrared (FTIR), X-ray diffraction (XRD) and digital
      fluorescence microscope. The as-synthesized microspheres PGMA, amino-modified
      PGMA (NH2-PGMA) and magnetic PGMA (M-PGMA) have a spherical shape with a smooth
      surface and fine monodispersity. M-PGMA microspheres are super-paramagnetic, and
      their saturated magnetic field is 4.608 emu.g-1, which made M-PGMA efficiently
      separable from aqueous solution by an external magnetic field. After
      poly(haxemethylene guanidine hydrochloride) (PHGH) functionalization, the
      resultant microspheres exhibit excellent antibacterial performance against both
      Gram-positive and Gram-negative bacteria. The fluorescence feature originating
      from the quantum dot CdTe endowed the hybrid microspheres with biological
      functions, such as targeted localization and biological monitoring functions.
      Combination of magnetism, antibiosis and fluorescence into one single hybrid
      microsphere opens up the possibility of the extensive study of multifunctional
      materials and widens the potential applications.

PMID- 23549272
TI  - A central role for thiols in plant tolerance to abiotic stress.
AB  - Abiotic stress poses major problems to agriculture and increasing efforts are
      being made to understand plant stress response and tolerance mechanisms and to
      develop new tools that underpin successful agriculture. However, the molecular
      mechanisms of plant stress tolerance are not fully understood, and the data
      available is incomplete and sometimes contradictory. Here, we review the
      significance of protein and non-protein thiol compounds in relation to plant
      tolerance of abiotic stress. First, the roles of the amino acids cysteine and
      methionine, are discussed, followed by an extensive discussion of the low
      molecular-weight tripeptide, thiol glutathione, which plays a central part in
      plant stress response and oxidative signalling and of glutathione-related
      enzymes, including those involved in the biosynthesis of non-protein thiol
      compounds. Special attention is given to the glutathione redox state, to
      phytochelatins and to the role of glutathione in the regulation of the cell
      cycle. The protein thiol section focuses on glutaredoxins and thioredoxins,
      proteins with oxidoreductase activity, which are involved in protein
      glutathionylation. The review concludes with a brief overview of and future
      perspectives for the involvement of plant thiols in abiotic stress tolerance.

PMID- 23549273
TI  - A functional variant of NEDD4L is associated with obesity and related phenotypes
      in a Han population of Southern China.
AB  - NEDD4L is a candidate gene for hypertension, both functionally and genetically.
      Recently, studies showed evidence for the association of NEDD4L with obesity, a
      key intermediate phenotype in hypertension. To further investigate the
      relationship between NEDD4L and body mass-related phenotypes, we genotyped three
      common variants (rs2288774, rs3865418 and rs4149601) in a population-based study
      of 892 unrelated Han Cantonese using the Sequenom MALDI-TOF-MS platform. Allele
      frequencies and genotype distribution were calculated in lean controls and
      overweight/obese cases and analyzed for association by the Chi-squared test and
      Logistic regression. Linear regression analysis was used to analyze the effect of
      individual genotypes on quantitative traits. Multivariate analyses demonstrated
      that the minor allele of rs4149601(A = 20.9%) was associated with a 2.60 kg, 2.78
      cm and 0.97 kg/m2 decrease per allele copy in weight, waist and BMI,
      respectively. Carriers of this allele also had a significant lower risk of
      overweight/obesity (p < 0.0001, OR = 0.52, 95% CI: 0.37-0.74) as compared to non
      carriers. However, no significant association between genotypes at rs2288774 and
      rs3865418 and covariate-adjusted overweight/obesity or any related phenotypes was
      observed. These results suggested that the functional variant of NEDD4L,
      rs4149601, may be associated with obesity and related phenotypes, and further
      genetic and functional studies are required to understand its role in the
      manifestation of obesity.

PMID- 23549275
TI  - Clinical utility gene card for: Catecholaminergic polymorphic ventricular
      tachycardia (CPVT).

PMID- 23549274
TI  - De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with
      VATER/VACTERL association.
AB  - The acronym VATER/VACTERL association describes the combination of at least three
      of the following congenital anomalies: vertebral defects (V), anorectal
      malformations (A), cardiac defects (C), tracheoesophageal fistula with or without
      esophageal atresia (TE), renal malformations (R), and limb defects (L). We aimed
      to identify highly penetrant de novo copy number variations (CNVs) that
      contribute to VATER/VACTERL association. Array-based molecular karyotyping was
      performed in a cohort of 41 patients with VATER/VACTERL association and 6
      patients with VATER/VACTERL-like phenotype including all of the patients'
      parents. Three de novo CNVs were identified involving chromosomal regions 1q41,
      2q37.3, and 8q24.3 comprising one (SPATA17), two (CAPN10, GPR35), and three
      (EPPK1, PLEC, PARP10) genes, respectively. Pre-existing data from the literature
      prompted us to choose GPR35 and EPPK1 for mouse expression studies. Based on
      these studies, we prioritized GPR35 for sequencing analysis in an extended cohort
      of 192 patients with VATER/VACTERL association and VATER/VACTERL-like phenotype.
      Although no disease-causing mutation was identified, our mouse expression studies
      suggest GPR35 to be involved in the development of the VATER/VACTERL phenotype.
      Follow-up of GPR35 and the other genes comprising the identified duplications is
      warranted. 

PMID- 23549276
TI  - Double-chambered left ventricle: coronary embolism as the first presentation of
      an extremely unusual cardiac anomaly.

PMID- 23549277
TI  - Epicardial fat volume correlates with severity of coronary artery disease in
      nonobese patients.
AB  - OBJECTIVE: It has been reported that epicardial adipose tissue could locally
      modulate the coronary artery functions through secretion of proinflammatory and
      anti-inflammatory cytokines. Epicardial fat tissue is further implicated in the
      pathogenesis of coronary artery disease (CAD) because of its proximity to the
      adventitia of the major epicardial coronary arteries. We investigated the
      relationship between epicardial fat volume (EFV) and severity of CAD in nonobese
      patients using 64-slice multidetector computed tomography (MDCT). METHODS: One
      hundred and forty nonobese patients (BMI <25 kg/m2) were enrolled. EFV and
      visceral fat area were measured by MDCT. Patients were classified according to
      the plaque components (noncalcified, mixed and calcified) and severity of CAD.
      Inflammatory biomarkers were also measured, and compared with each CT parameter.
      RESULTS: EFV was significantly correlated with the extent or severity of CAD.
      Patients with noncalcified or mixed plaque had a greater EFV than those with
      calcified plaque. Log-transferred high sensitivity C-reactive protein (CRP) was
      significantly correlated with EFV (r = 0.24, P = 0.04). Adiponectin level was
      significantly inversely correlated with visceral fat area (r = 0.38, P = 0.0001).
      CONCLUSION: Increased EFV is associated with more severe CAD and noncalcified or
      mixed coronary plaques in nonobese patients.

PMID- 23549278
TI  - Positional oxygen desaturation: the spectrum of postural changes in arterial
      oxygen is wider than the pure platypnea-orthodeoxia syndrome.

PMID- 23549279
TI  - From short pulses to short breaks: exotic plasma bullets via residual electron
      control.
AB  - Plasma plumes with exotically segmented channel structure and plasma bullet
      propagation are produced in atmospheric plasma jets. This is achieved by
      tailoring interruptions of a continuous DC power supply over the time scales of
      lifetimes of residual electrons produced by the preceding discharge phase. These
      phenomena are explained by studying the plasma dynamics using nanosecond
      precision imaging. One of the plumes is produced using 2 - 10 MUs interruptions
      in the 8 kV DC voltage and features a still bright channel from which a
      propagating bullet detaches. A shorter interruption of 900 ns produces a plume
      with the additional long conducting dark channel between the jet nozzle and the
      bright area. The bullet size, formation dynamics, and propagation speed and
      distance can be effectively controlled. This may lead to micrometer- and
      nanosecond-precision delivery of quantized plasma bits, warranted for next
      generation health, materials, and device technologies.

PMID- 23549280
TI  - High-performance low-bandgap conjugated polymers bearing diethynylanthracene
      units for thin-film transistors.
AB  - Novel donor-acceptor pi-conjugated copolymers, P(DPP-BDT) and P(DPP-ANT), were
      synthesized in 87-89% yield. Thin-film transistors (TFTs) made from the thermally
      annealed film of P(DPP-ANT) exhibited much better performance (e.g., MUmax = 1.90
      cm(2) V(-1) s(-1), Ion/off ~ 10(6)) than those made from the thermally annealed
      film of P(DPP-BDT).

PMID- 23549282
TI  - Isolation and structure elucidation of three new dolastanes from the brown alga
      Dilophus spiralis.
AB  - Three new dolastane diterpenes (1-3) and five previously reported
      perhydroazulenes were isolated from the organic extracts of the brown alga
      Dilophus spiralis. The structure elucidation and the assignment of the relative
      configurations of the isolated natural products were based on extensive analyses
      of their spectroscopic data, whereas the absolute configuration of metabolite 2
      was determined through its chemical conversion to a previously isolated compound
      of known configuration.

PMID- 23549281
TI  - 6"-Debromohamacanthin A, a bis (indole) alkaloid, inhibits angiogenesis by
      targeting the VEGFR2-mediated PI3K/AKT/mTOR signaling pathways.
AB  - Hamacanthins, bis (indole) alkaloids, are found in a few marine sponges,
      including Spongosorites sp. Hamacanthins have been shown to possess cytotoxic,
      antibacterial and antifungal activities. However, the precise mechanism for the
      biological activities of hamacanthins has not yet been elucidated. In the present
      study, the anti-angiogenic effects of 6"-debromohamacanthin A (DBHA), an active
      component of isolated hamacanthins, were evaluated in cultured human umbilical
      vascular endothelial cells (HUVEC) and endothelial-like cells differentiated from
      mouse embryonic stem (mES) cells. DBHA significantly inhibited vascular
      endothelial growth factor (VEGF)-induced cell proliferation, migration and tube
      formation in the HUVEC. DBHA also suppressed the capillary-like structure
      formation and the expression of platelet endothelial cell adhesion molecule
      (PECAM), an endothelial biomarker, in mES cell-derived endothelial-like cells. To
      further understand the precise molecular mechanism of action, VEGF-mediated
      signaling pathways were analyzed in HUVEC cells and mES cell-derived endothelial
      like cells. DBHA suppressed the VEGF-induced expression of MAPKs (p38, ERK and
      SAPK/JNK) and the PI3K/AKT/mTOR signaling pathway. In addition, DBHA inhibited
      microvessel sprouting in mES/EB-derived embryoid bodies. In an ex vivo model,
      DBHA also suppressed the microvessel sprouting of mouse aortic rings. The
      findings suggest for the first time that DBHA inhibits angiogenesis by targeting
      the vascular endothelial growth factor receptor 2 (VEGFR2)-mediated PI3K/AKT/mTOR
      signaling pathway in endothelial cells.

PMID- 23549283
TI  - An HPLC method for microanalysis and pharmacokinetics of marine sulfated
      polysaccharide PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles in
      rat plasma.
AB  - This study was aimed at developing a sensitive and selective HPLC method with
      postcolumn fluorescence derivatization for the detection of propylene glycol
      alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a
      simple and fast ultrafiltration method. PSS was extracted from rat plasma with D
      glucuronic acid as internal standard. Isocratic chromatographic separation was
      performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium
      sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by
      fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using
      guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium
      at 120  degrees C. The calibration curve was linear over a concentration range of
      1-500 MUg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL.
      This validated method was applied successfully to the pharmacokinetic study of
      PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in
      rat plasma after a single intravenous (PSS only) and oral administration (PSS and
      PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS
      and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10%
      compared with PSS which shows that PSS-NP can improve oral bioavailability.

PMID- 23549284
TI  - Biological activities of ethanolic extracts from deep-sea Antarctic marine
      sponges.
AB  - We report on the screening of ethanolic extracts from 33 deep-sea Antarctic
      marine sponges for different biological activities. We monitored hemolysis,
      inhibition of acetylcholinesterase, cytotoxicity towards normal and transformed
      cells and growth inhibition of laboratory, commensal and clinically and
      ecologically relevant bacteria. The most prominent activities were associated
      with the extracts from sponges belonging to the genus Latrunculia, which show all
      of these activities. While most of these activities are associated to already
      known secondary metabolites, the extremely strong acetylcholinesterase inhibitory
      potential appears to be related to a compound unknown to date. Extracts from
      Tetilla leptoderma, Bathydorus cf. spinosus, Xestospongia sp., Rossella sp.,
      Rossella cf. racovitzae and Halichondria osculum were hemolytic, with the last
      two also showing moderate cytotoxic potential. The antibacterial tests showed
      significantly greater activities of the extracts of these Antarctic sponges
      towards ecologically relevant bacteria from sea water and from Arctic ice. This
      indicates their ecological relevance for inhibition of bacterial microfouling.

PMID- 23549285
TI  - Spongiatriol inhibits nuclear factor kappa B activation and induces apoptosis in
      pancreatic cancer cells.
AB  - Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly
      resistant to all current chemotherapies, and its growth is facilitated by chronic
      inflammation. The majority of pro-inflammatory cytokines initiate signaling
      cascades that converge at the activation of the Nuclear Factor Kappa B
      (NFkappaB), a signal transduction molecule that promotes cell survival,
      proliferation and angiogenesis. In an effort to identify novel inhibitors of
      NFkappaB, the HBOI library of pure compounds was screened using a reporter cell
      line that produces luciferin under the transcriptional control of NFkappaB. Seven
      compounds were identified through this screen, but in the case of five of them,
      their reported mechanism of action made them unlikely to be specific NFkappaB
      inhibitors. Spongiatriol, a marine furanoditerpenoid that was first isolated in
      the 1970s, is shown here to inhibit NFkappaB transcriptional activity in a
      reporter cell line, to reduce levels of phosphorylated (active) NFkappaB in the
      AsPC-1 cell line, to have an IC50 for cytotoxicity in the low micromolar range
      against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines,
      and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc
      1 cell lines.

PMID- 23549286
TI  - Hormetic effects of acute methylmercury exposure on grp78 expression in rat brain
      cortex.
AB  - This study aims to explore the expression of GRP78, a marker of endoplasmic
      reticulum (ER) stress, in the cortex of rat brains acutely exposed to
      methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into
      six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of
      MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA
      expression of Grp78 were detected by western blotting and real-time PCR,
      respectively. The results showed that a gradual increase in GRP78 protein
      expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6
      mg/kg). Protein levels peaked in the 6 mg/kg group (p < 0.05 vs. controls),
      decreased in the 8 mg/kg group, and bottomed below the control level in the 10
      mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be
      implied that acute exposure to MeHg induced hormetic dose-dependent changes in
      Grp78 mRNA and protein expression, suggesting that activation of ER stress is
      involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78
      protein expression to stimulate endogenous cytoprotective mechanisms.

PMID- 23549287
TI  - Architecture of the Pol III-clamp-exonuclease complex reveals key roles of the
      exonuclease subunit in processive DNA synthesis and repair.
AB  - DNA polymerase III (Pol III) is the catalytic alpha subunit of the bacterial DNA
      Polymerase III holoenzyme. To reach maximum activity, Pol III binds to the DNA
      sliding clamp beta and the exonuclease epsilon that provide processivity and
      proofreading, respectively. Here, we characterize the architecture of the Pol III
      clamp-exonuclease complex by chemical crosslinking combined with mass
      spectrometry and biochemical methods, providing the first structural view of the
      trimeric complex. Our analysis reveals that the exonuclease is sandwiched between
      the polymerase and clamp and enhances the binding between the two proteins by
      providing a second, indirect, interaction between the polymerase and clamp. In
      addition, we show that the exonuclease binds the clamp via the canonical binding
      pocket and thus prevents binding of the translesion DNA polymerase IV to the
      clamp, providing a novel insight into the mechanism by which the replication
      machinery can switch between replication, proofreading, and translesion
      synthesis.

PMID- 23549288
TI  - Inhibition of neointima formation through DNA vaccination for apolipoprotein(a):
      a new therapeutic strategy for lipoprotein(a).
AB  - Lipoprotein(a) [Lp(a)] is an unique lipoprotein consisting of the glycoprotein
      apolipoprotein(a) [apo(a)] in low-density lipoprotein. Although Lp(a) is a well
      known independent risk factor for cardiovascular disease; however, there is no
      drugs to decrease plasma Lp(a) level. Thus, to inhibit the biological activity of
      Lp(a), we developed DNA vaccine for apo(a) by the targeting to the selected 12
      hydrophilic amino acids in the kringle-4 type 2 domain of apo(a). Hepatitis B
      virus core protein was used as an epitope carrier to enhance the immunogenicity.
      Intramuscular immunization with apo(a) vaccine resulted in the significant
      inhibition of neointima formation in carotid artery ligation model using Lp(a)
      transgenic mice, associated with anti-apo(a) antibody and decrease in vascular
      Lp(a) deposition. Overall, this study provided the first evidence that the pro
      atherosclerotic actions of Lp(a) could be prevented by DNA vaccine directed
      against apo(a), suggesting a novel therapeutic strategy to treat cardiovascular
      diseases related to high Lp(a).

PMID- 23549289
TI  - Origin of electrolyte-dopant dependent sulfur poisoning of SOFC anodes.
AB  - The mechanisms governing the sulfur poisoning of the triple phase boundary (TPB)
      of Ni-XSZ (X2O3 stabilized zirconia) anodes have been investigated using density
      functional theory. The calculated sulfur adsorption energies reveal a clear
      correlation between the size of the cation dopant X(3+) and the sulfur tolerance
      of the Ni-XSZ anode; the smaller the ionic radius, the higher the sulfur
      tolerance. The mechanistic study shows that the size of X(3+) strongly influences
      XSZ's surface energy, which in turn determines the adhesion of Ni to XSZ. The Ni
      XSZ interaction has a direct impact on the Ni-S interaction and on the relative
      stability of reconstructed and pristine Ni(100) facets at the TPB. Together,
      these two effects control the sulfur adsorption on the Ni atoms at the TPB. The
      established relationships explain experimentally observed dopant-dependent anode
      performances and provide a blueprint for the future search for and preparation of
      highly sulfur tolerant anodes.

PMID- 23549290
TI  - Stepwise replacement of nickel with cobalt ions in a [Ni6] cluster.
AB  - Polydentate ligands were used to support planar methoxo-bridged {Ni(6-x)Co(x)} (x
      = 0, 1 or 2) clusters which were structurally characterized by single crystal
      analyses. The homometallic {Ni6} complex displayed overall ferrimagnetic
      interactions between metal centres, and increasing the cobalt content led to a
      proportional increase in ac-response.

PMID- 23549291
TI  - Prospective case series on trabecular-iris angle status after an acute episode of
      phacomorphic angle closure.
AB  - AIM: To investigate the trabecular-iris angle with ultrasound biomicroscopy (UBM)
      post cataract extraction after an acute attack of phacomorphic angle closure.
      METHODS: This prospective study involved 10 cases of phacomorphic angle closure
      that underwent cataract extraction and intraocular lens insertion after
      intraocular pressure (IOP) lowering. Apart from visual acuity and IOP, the
      trabecular-iris angle was measured by gonioscopy and UBM at 3 months post attack.
      RESULTS: In 10 consecutive cases of acute phacomorphic angle closure from
      December 2009 to December 2010, gonioscopic findings showed peripheral anterior
      synechiae (PAS) <= 90 degrees  in 30% of phacomorphic patients and a mean Shaffer
      grading of (3.1+/-1.0). UBM showed a mean angle of (37.1 degrees +/-4.5 degrees )
      in the phacomorphic eye with the temporal quadrant being the most opened and
      (37.1 degrees +/-8.0 degrees ) in the contralateral uninvolved eye. The mean time
      from consultation to cataract extraction was (1.4+/-0.7) days and the mean total
      duration of phacomorphic angle closure was (3.6+/-2.8) days but there was no
      correlation to the degree of angle closure on UBM (Spearman correlation P=0.7).
      The presenting mean IOP was (50.5+/-7.4) mmHg and the mean IOP at 3 months was
      (10.5+/-3.4) mmHg but there were no correlations with the degree of angle closure
      (Spearman correlations P=0.9). CONCLUSION: An open trabecular-iris angle and
      normal IOP can be achieved after an acute attack of phacomorphic angle closure if
      cataract extraction is performed within 1 day - 2 days after IOP control.
      Gonioscopic findings were in agreement with UBM, which provided a more specific
      and object angle measurement. The superior angle is relatively more narrowed
      compared to the other quadrants. All contralateral eyes in this series had open
      angles.

PMID- 23549292
TI  - Dandelion-shaped nanostructures for enhancing omnidirectional photovoltaic
      performance.
AB  - Broadband and omnidirectional light harvesting is important in photovoltaic
      technology because of its wide spectral range of radiation and the sun's
      movement. This study reports the fabrication and characterization of zinc oxide
      (ZnO) dandelions on Cu(In,Ga)Se2 (CIGS) solar cells. The fabrication of
      dandelions involves the combination of self-assembled polystyrene (PS)
      nanospheres and the hydrothermal method, which is one of the simplest and
      cheapest methods of fabricating a three-dimensional, closely packed periodic
      structure. This study also investigates the optimization on dimension of the PS
      nanospheres using the rigorous coupled-wave analysis (RCWA) method. This study
      uses an angle-resolved reflectance spectroscope and a homemade rotatable photo I
      V measurement to investigate the omnidirectional and broadband antireflections of
      the proposed dandelion structure. Under a simulated one-sun condition and a light
      incident angle of up to 60 degrees , cells with ZnO dandelions arrays enhanced
      the short-circuit current density by 31.87%. Consequently, ZnO dandelions are
      suitable for creating an omnidirectionally antireflective coating for
      photovoltaic devices.

PMID- 23549293
TI  - Inducible graphene oxide probe for high-specific tumor diagnosis.
AB  - A revolutionary probe was constructed by conjugating Cy5 on a graphene oxide
      sheet. The fluorescence was quenched owing to its proximity to graphene oxide in
      normal circumstances, but lit on arriving at the tumor site. Both in vitro and in
      vivo studies demonstrated that the probe exhibits great potential for tumor
      diagnosis.

PMID- 23549294
TI  - Relationship of postoperative recatheterization and intraoperative bladder
      distention volume in holmium laser enucleation of the prostate for benign
      prostatic hyperplasia.
AB  - PURPOSE: The purpose of this study was to identify the risk factors for
      recatheterization after holmium laser enucleation of the prostate (HoLEP).
      MATERIALS AND METHODS: A total of 166 consecutive patients treated with HoLEP by
      a single surgeon from January 2010 to June 2011 were enrolled in this study. We
      collected data on preoperative and intraoperative parameters, including
      intraoperative bladder distention volume. The patients were divided into two
      groups. Group 1 included patients who voided successfully after removal of the
      catheter, and group 2 included patients who required recatheterization. Analysis
      and comparison of the perioperative parameters of both groups was performed for
      identification of risk factors for recatheterization. RESULTS: Recatheterization
      was required in 9 of 166 (5.4%) patients. No significant differences in age or
      preoperative parameters, including prostate-specific antigen, prostate volume,
      International Prostate Symptom Score, peak flow rate, postvoid residual urine,
      maximal bladder capacity, and Abrahams Griffiths number, were observed between
      the two groups. Of the intraoperative parameters, intraoperative bladder
      distention volume was significantly smaller in group 1 than in group 2 (700.65 mL
      vs. 897.78 mL, p<0.001). In the multivariate logistic regression analysis, after
      adjustment for other variables, intraoperative bladder distention volume was
      found to be a statistically significant risk factor for postoperative
      recatheterization (hazard ratio, 1.006; confidence interval, 1.002 to 1.010;
      p=0.002). CONCLUSIONS: Nine of 166 (5.4%) patients failed to void after HoLEP and
      required catheterization. Intraoperative bladder distention volume was found to
      be a statistically significant risk factor for recatheterization in this patient
      group.

PMID- 23549295
TI  - Patient and program characteristics of early outpatient cardiac rehabilitation
      programs in the United States.
AB  - PURPOSE: The purpose of this study was to perform a brief survey to determine the
      patient and program characteristics associated with early outpatient cardiac
      rehabilitation (EOCR) in the United States. METHODS: To assess these
      characteristics, a brief survey (13 items, some with multiple responses) was sent
      by the American Association of Cardiovascular and Pulmonary Rehabilitation
      (AACVPR) to all program administrators or directors on the AACVPR mailing list in
      2009. RESULTS: Responses were received from 138 program administrators or
      directors in 44 states, accounting for 19 689 patients who completed at least 1
      EOCR exercise session. More men (68%) were enrolled in EOCR programs, and the 3
      most prevalent primary diagnoses were percutaneous coronary intervention or stent
      (31%), coronary artery bypass graft surgery (30%), and myocardial infarction
      (22%). Seventy-two percent of responding programs were AACVPR certified and had
      staff trained primarily (66%) in either nursing or exercise physiology. Eighty
      four percent of the programs offered an outpatient maintenance cardiac
      rehabilitation program, and 62% were located in a rural setting. CONCLUSIONS:
      This study provides valuable information on use and patient demographics of EOCR
      programs in the United States. This information may be beneficial for health care
      professionals, health care institutions, third-party payers, and regulatory
      agencies that seek to quantify health care quality.

PMID- 23549296
TI  - Lanthanide-mediated dephosphorylation used for peptide cleavage during solid
      phase peptide synthesis.
AB  - Lanthanide(III) ions can accelerate the hydrolysis of phosphomonoesters and
      phosphodiesters in neutral aqueous solution. In this paper, lanthanide-mediated
      dephosphorylation has been applied in aqueous media as an orthogonal cleavage
      condition that can be employed in conventional solid phase peptide synthesis
      (SPPS). A phosphorylated polymeric support for SPPS was developed using Boc
      chemistry. The cleavage of resin-bound phosphates was investigated with the
      addition of Eu(III), Yb(III), acid or base, a mixture of solvents or different
      temperatures. To demonstrate the utility of this approach for SPPS, a peptide
      sequence was synthesized on a phosphorylated polymeric support and quantitatively
      cleaved with lanthanide ions in neutral aqueous media. The protecting groups for
      side chains were retained during peptide cleavage using lanthanide ions. This new
      methodology provides a mild orthogonal cleavage condition of phosphoester as a
      linker during SPPS.

PMID- 23549297
TI  - Synthesis of a pseudodisaccharide alpha-C-glycosidically linked to an 8-alkylated
      guanine.
AB  - The synthesis of stable guanofosfocin analogues has attracted considerable
      attention in the past 15 years. Several guanofosfocin analogues mimicking the
      three constitutional elements of mannose, ribose, and guanine were designed and
      synthesized. Interest in ether-linked pseudodisaccharides and 8-alkylated
      guanines is increasing, due to their potential applications in life science. In
      this article, a novel guanofosfocin analogue 6, an ether-linked
      pseudodisaccharide connected alpha-C-glycosidically to an 8-alkylated guanine,
      was synthesized in a 10-longest linear step sequence from known diol 13,
      resulting in an overall yield of 26%. The key steps involve the ring-opening of
      cyclic sulfate 8 by alkoxide generated from 7 and a reductive cyclization of 4-N
      acyl-2,4-diamino-5-nitrosopyrimidine 19 to form compound 6.

PMID- 23549298
TI  - Bisucaberin B, a linear hydroxamate class siderophore from the marine bacterium
      Tenacibaculum mesophilum.
AB  - A siderophore, named bisucaberin B, was isolated from Tenacibaculum mesophilum
      bacteria separated from a marine sponge collected in the Republic of Palau. Using
      spectroscopic and chemical methods, the structure of bisucaberin B (1) was
      clearly determined to be a linear dimeric hydroxamate class siderophore. Although
      compound 1 is an open form of the known macrocyclic dimer bisucaberin (2), and
      was previously described as a bacterial degradation product of desferrioxamine B
      (4), the present report is the first description of the de novo biosynthesis of
      1. To the best of our knowledge, compound 1 is the first chemically characterized
      siderophore isolated from a bacterium belonging to the phylum Bacteroidetes.

PMID- 23549299
TI  - Haemodynamic monitoring using arterial waveform analysis.
AB  - PURPOSE OF REVIEW: To describe the theory behind arterial waveform analysis, the
      different variables that may be obtained using this method, reliability of
      measurements and their clinical relevance. Areas for future research are
      identified. RECENT FINDINGS: The precision of cardiac output (CO) measurements
      varies considerably and deteriorates during haemodynamic instability. Significant
      device-to-device differences exist. Nevertheless, most are sufficiently accurate
      for tracking changes in CO. Targeted intervention guided by haemodynamic
      monitoring reduces mortality and morbidity in high-risk surgical patients.
      Dynamic changes in variables such as systolic pulse variation, pulse pressure
      variation (PPV) and stroke volume variation (SVV) may be useful for evaluating
      fluid responsiveness, although important caveats exist. Newer indices such as PPV
      : SVV ratio may be useful in identifying preload and vasopressor-dependent
      patients. Peripheral arterial dP/dt has not been validated in critically ill
      patients and requires further investigation. SUMMARY: Despite significant
      limitations in measurement accuracy and inter-device differences, arterial
      waveform analysis is a potentially useful tool for monitoring the central
      circulation in critically ill patients. Future studies investigating the effects
      of haemodynamic management guided by arterial waveform variables in critically
      ill patients are urgently needed. The evaluation of cardiopulmonary interactions
      and usefulness of dP/dt are other areas that require further investigation.

PMID- 23549300
TI  - Thermodynamics of oligomer formation: implications for secondary organic aerosol
      formation and reactivity.
AB  - Dimers and higher order oligomers, whether in the gas or particle phase, can
      affect important atmospheric processes such as new particle formation, and gas
      particle partitioning. In this study, the thermodynamics of dimer formation from
      various oxidation products of alpha-pinene ozonolysis are investigated using a
      combination of Monte Carlo configuration sampling, semi-empirical and density
      functional theory (DFT) quantum mechanics, and continuum solvent modeling.
      Favorable dimer formation pathways are found to exist in both gas and condensed
      phases. The free energies of dimer formation are used to calculate equilibrium
      constants and expected dimer concentrations under a variety of conditions. In the
      gas phase, favorable pathways studied include formation of non-covalent dimers of
      terpenylic acid and/or cis-pinic acid and a covalently-bound peroxyhemiacetal.
      Under atmospherically relevant conditions, only terpenylic acid forms a dimer in
      sufficient quantities to contribute to new particle formation. Under conditions
      typically used in laboratory experiments, several dimer formation pathways may
      contribute to particle formation. In the condensed phase, non-covalent dimers of
      terpenylic acid and/or cis-pinic acid and covalently-bound dimers representing a
      peroxyhemiacetal and a hydrated aldol are favorably formed. Dimer formation is
      both solution and temperature dependent. A water-like solution appears to promote
      dimer formation over methanol- or acetonitrile-like solutions. Heating from 298 K
      to 373 K causes extensive decomposition back to monomers. Dimers that are not
      favorably formed in either the gas or condensed phase include hemi-acetal, ester,
      anhydride, and the di(alpha-hydroxy) ether.

PMID- 23549301
TI  - A computational study of the mechanism of CO oxidation by a ceria supported
      surface rhodium oxide layer.
AB  - A mechanism of CO oxidation by a thin surface oxide of Rh supported on ceria is
      proposed: CO is oxidized by the Rh-oxide film, which is subsequently reoxidized
      by a ceria surface O atom. The proposed mechanism is supported by in situ Raman
      spectroscopic investigations.

PMID- 23549302
TI  - The facile assembly of bis-, tris- and poly(triazaphosphole) systems using
      "click" chemistry.
AB  - Uncatalysed 1,3-dipolar cycloaddition reactions between two phosphaalkynes, P=CR
      (R = Bu(t) or Me), and a series of di-, tri- and poly-azido precursor compounds
      have given very high yields of a range of triazaphosphole substituted systems.
      These comprise the 1,1'-bis(triazaphosphole)ferrocenes, [Fe{C5H4(N3PCR)}2], the
      tris(triazaphosphole)cyclohexane, cis-1,3,5-C6H9(N3PCBu(t))3, and the
      poly(allyltriazaphosphole)s, {C3H5(N3PCR)}infinity. Electrochemical studies on
      the 1,1'-bis(triazaphosphole)ferrocenes reveal the compounds to undergo
      reversible 1-electron oxidation processes, at significantly more positive
      potentials than ferrocene itself. Attempts to chemically oxidise one 1,1'
      bis(triazaphosphole)ferrocene with a silver salt, Ag[Al{OC(CF3)3}4] were not
      successful, and led to the formation of a silver coordination complex, [{Fe[MU
      C5H4(N3PCBu(t))]2(MU-Ag)}2][Al{OC(CF3)3}4]2, thereby demonstrating the potential
      the reported triazaphosphole substituted systems possess as novel ligands in
      coordination chemistry.

PMID- 23549304
TI  - "The skill is using your big head over your little head": what black heterosexual
      men say they know, want, and need to prevent HIV.
AB  - Although the disproportionate toll of HIV/AIDS among Black heterosexuals,
      particularly in low-income U.S. urban areas is well documented, Black
      heterosexual men are rarely the explicit focus of HIV prevention messages,
      research, and interventions. We conducted 4 focus groups with 28 Black men, aged
      19 to 51 years, who were enrolled in the workforce and fatherhood development
      program of a local community-based organization to examine (a) the priority and
      role of HIV/AIDS in their lives and (b) their HIV prevention needs. Although none
      articulated HIV as a top life priority, respondents nonetheless prioritized
      educating their children about HIV prevention and protecting their main partners
      from HIV if they had other sexual partners. Analyses demonstrated that
      participants said they wanted and needed: to learn how to talk to partners about
      HIV testing and use condoms when tempted not to do so, and more discussion
      oriented educational opportunities to learn and exchange prevention strategies. 

PMID- 23549303
TI  - Insights into the increasing virulence of the swine-origin pandemic H1N1/2009
      influenza virus.
AB  - Pandemic H1N1/2009 viruses have been stabilized in swine herds, and some strains
      display higher pathogenicity than the human-origin isolates. In this study, high
      throughput RNA sequencing (RNA-seq) is applied to explore the systemic
      transcriptome responses of the mouse lungs infected by swine (Jia6/10) and human
      (LN/09) H1N1/2009 viruses. The transcriptome data show that Jia6/10 activates
      stronger virus-sensing signals, such as the toll-like receptor, RIG-I like
      receptor and NOD-like receptor signalings, as well as a stronger NF-kappaB and
      JAK-STAT signals, which play significant roles in inducing innate immunity. Most
      cytokines and interferon-stimulated genes show higher expression lever in Jia/06
      infected groups. Meanwhile, virus Jia6/10 activates stronger production of
      reactive oxygen species, which might further promote higher mutation rate of the
      virus genome. Collectively, our data reveal that the swine-origin pandemic
      H1N1/2009 virus elicits a stronger innate immune reaction and pro-oxidation
      stimulation, which might relate closely to the increasing pathogenicity.

PMID- 23549305
TI  - Manipulating dynamics with chemical structure: probing vibrationally-enhanced
      tunnelling in photoexcited catechol.
AB  - Ultrafast time-resolved velocity map ion imaging (TR-VMI) and time-resolved ion
      yield (TR-IY) methods are utilised to reveal a comprehensive picture of the
      electronic state relaxation dynamics in photoexcited catechol (1,2
      dihydroxybenzene). After excitation to the S1 ((1)pipi*) state between 280.5 (the
      S1 origin band, S1(v = 0)) to 243 nm, the population in this state is observed to
      decay through coupling onto the S2 ((1)pisigma*) state, which is dissociative
      with respect to the non-hydrogen bonded 'free' O-H bond (labelled O(1)-H). This
      process occurs via tunnelling under an S1/S2 conical intersection (CI) on a
      timeframe of 5-11 ps, resulting in O(1)-H bond fission along S2. Concomitant
      formation of ground state catechoxyl radicals (C6H5O2(X)), in coincidence with
      translationally excited H-atoms, occurs over the same timescale as the S1 state
      population decays. Between 254-237 nm, direct excitation to the S2 state is also
      observed, manifesting in the ultrafast (~100 fs) formation of H-atoms with high
      kinetic energy release. From these measurements we determine that the S1/S2 CI
      lies ~3700-5500 cm(-1) above the S1(v = 0) level, indicating that the barrier
      height to tunnelling from S1(v = 0) -> S2 is comparable to that observed in the
      related 'benchmark' species phenol (hydroxybenzene). We discuss how a highly
      'vibrationally-enhanced' tunnelling mechanism is responsible for the two orders
      of magnitude enhancement to the tunnelling rate in catechol, relative to that
      previously determined in phenol (>1.2 ns), despite similar barrier heights. This
      phenomenon is a direct consequence of the non-planar S1 excited state minimum
      structure (C1 symmetry) in catechol, which in turn yields relaxed symmetry
      constraints for vibronic coupling from S1(v = 0) -> S2- a scenario which does not
      exist for phenol. These findings offer an elegant example of how even simple
      chemical modifications (ortho-hydroxy substitution) to a fundamental,
      biologically relevant, UV chromophore, such as phenol, can have profound effects
      on the ensuing excited state dynamics.

PMID- 23549307
TI  - Recent advances in adrenocortical carcinoma in adults.
AB  - PURPOSE OF REVIEW: Adrenocortical cancer (ACC) is a rare and often aggressive
      malignancy. The overall 5-year survival rate of ACC is less than 30% in part
      owing to advanced stage of the disease at diagnosis and limited efficiency of
      therapies when initial surgery is not curative. So far, studies with large
      cohorts of patients affected by ACC were lacking because of the rarity of the
      disease; however, recent international and multicenter collaborative studies
      provide new insights in the management of ACC. RECENT FINDINGS: This review
      summarizes recent findings in the genetic, hormonal evaluation, imaging, and
      therapies of ACC in adults. There is new promise for the use of 2-[fluorine
      18]fluoro-2-deoxy-D-glucose-positron emission tomography and metomidate in
      initial diagnosis and follow-up. Limited studies support benefit of specific
      surgical approaches such as loco-regional lymph node dissection and
      metastasectomy in specific subgroups. New developments in the use of mitotane
      therapy and its drug interactions, on adjuvant radiotherapy and prospective data
      on combined chemotherapy, have appeared recently. SUMMARY: These recent findings
      will provide more evidence-based recommendations in the future to better assist
      clinicians in the management of patients with ACC. However, there is still an
      important need to understand the molecular mechanisms underlying this disease to
      design better therapeutic approaches.

PMID- 23549308
TI  - The prepubertal testis: biomarkers and functions.
AB  - PURPOSE OF REVIEW: Biomarkers of prepubertal testicular function have become
      widely available only in recent years. The aim of this review is to update the
      knowledge on key biomarkers used to assess hypogonadism in boys. RECENT FINDINGS:
      Sertoli cells are the most representative cells of the prepubertal testis. Anti
      Mullerian hormone and inhibin B are essential biomarkers of Sertoli cell
      function. Also, INSL3 arises as an additional marker of Leydig cell dysfunction.
      SUMMARY: The widespread use of these biomarkers has enhanced our knowledge on the
      pathophysiology and diagnosis of prepubertal male hypogonadism. Beyond their well
      known germ-cell toxicity, oncologic treatments may also affect Sertoli cell
      function. Pathophysiology is not the same in all aneuploidies leading to
      infertility: while hypogonadism is not evident until mid-puberty in Klinefelter
      syndrome, it is established in early infancy in Down syndrome. In Noonan
      syndrome, the occurrence of primary hypogonadism depends on the existence of
      cryptorchidism, and Prader-Willi syndrome may present with either primary or
      combined forms of hypogonadism. Prepubertal testicular markers have also provided
      insights into the effects of environmental disruptors on gonadal function from
      early life, and helped dissipate concerns about testicular function in boys born
      preterm or small for gestational age or conceived by assisted reproductive
      technique procedures.

PMID- 23549310
TI  - Minimal invasive midvastus versus standard parapatellar approach in total knee
      arthroplasty.
AB  - OBJECTIVE: The aim of this study was to compare the short-term results of total
      knee arthroplasty (TKA) surgeries performed with minimally invasive mini
      midvastus (MMV) incision and the standard medial parapatellar technique (ST).
      METHODS: Twenty patients (18 males, 2 females; mean age: 67.25+/-6.70) operated
      with the ST and 19 patients (4 males, 15 females; mean age: 64.53+/-7.53)
      operated with the MMV approach were retrospectively evaluated. The surgery time,
      blood loss, time to straight leg raise (SLR) postoperatively, range of motion
      (ROM) and Knee Society (KSS) score and Hospital for Special Surgery (HSS) score
      were compared between the groups. Radiological evaluation was made with standing
      orthoroentgenographs both pre- and postoperatively. Mean follow-up time was
      29.4+/-8.2 months in the ST and 17.7+/-11.1 months in the MMV group. RESULTS: In
      the early postoperative period (10th day), the MMV group was significantly better
      than the ST group in terms of ROM. Time to SLR and blood loss values were also
      significantly better in the MMV group. However, there was no significant
      difference between the groups after the sixth month, for ROM, KSS and HSS values
      (p>0.05). Surgery time was significantly longer (with a mean difference of 22
      minutes) in the MMV group. Radiological examination revealed ideal alignment in
      both groups. No deep or superficial infection was detected. Two patients in the
      MMV group had skin problems which healed after clinical follow-up. CONCLUSION:
      Our results suggested that functional results of TKAs performed via the MMV
      approach are better in the first six months when compared to those of the ST.

PMID- 23549311
TI  - The effect of computerized navigation on component alignment in total knee
      arthroplasty.
AB  - OBJECTIVE: The aim of this retrospective cross-sectional study was to evaluate
      the effect of computer-assisted total knee arthroplasty (TKA) on component
      alignment. METHODS: The radiographs of 20 patients who underwent computer
      assisted TKA within a two-year period were analyzed with respect to the
      mechanical femorotibial, mechanical femoral, mechanical tibial angles (mFTA, mFA
      and mTA, respectively) and the tibial slope (sigma). RESULTS: The mean
      postoperative mFTA (179.7 degrees ) was significantly improved when compared to
      the preoperative value (175.45 degrees ) (p=0.012). The mean postoperative mFA
      was significantly reduced (p=0.035) in comparison with the preoperative mean
      (89.1 degrees  and 90.6 degrees , respectively). The mean postoperative mTA was
      exactly 90.0 degrees , while the preoperative mean was significantly lower (87.7
      degrees ; p=0.003). Mean tourniquet time during TKA was 109.5 minutes.
      CONCLUSION: Computer navigation in TKA appears to be a reliable system which
      facilitates implant positioning and component alignment.

PMID- 23549312
TI  - Prediction of the quadruple hamstring autograft thickness in ACL reconstruction
      using anthropometric measures.
AB  - OBJECTIVE: The aim of this study was to determine whether simple anthropometric
      measurements, such as height, weight, body mass index (BMI), age, and thigh
      circumference can be used to accurately predict the diameter of hamstring tendons
      for anterior cruciate ligament (ACL) reconstruction surgery. METHODS: One hundred
      sixty-four consecutive male patients who underwent ACL reconstruction using
      quadruple hamstring autograft between January 2010 and December 2011 were
      prospectively evaluated. Anthropometric measurements including height, weight,
      BMI, age and thigh circumference were recorded preoperatively. The thickness of
      the quadruple hamstring autograft was intraoperatively determined using sizing
      cylinders. Correlation coefficients (Pearson's r) and stepwise, multiple linear
      regression were used to determine the relationship between the outcome variable
      (hamstring graft diameter) and the predictor variables (age, height, weight, BMI,
      thigh circumference). RESULTS: Correlation analysis revealed a positive relation
      between the height, weight and graft thickness (p=0.000 and p=0.002,
      respectively). Taller and heavier patients tended to have thicker quadrupled
      hamstring graft. However, age, thigh circumference, and BMI did not correlate
      with the graft thickness (p=0.700, p=0.290 and p=0.727, respectively). Stepwise,
      multiple linear regression indicated that height was statistically important as a
      predictor for hamstring graft diameter (R2=0.157, p=0.0001) and yielded the
      following regression equation for predicting quadrupled hamstring graft
      thickness: graft thickness = [(height in cm) x 0.052) - 1.07] mm. CONCLUSION:
      Height can be used as a practical and accurate measurement to preoperatively
      predict quadruple hamstring graft diameter in male patients. Identification of
      possible hamstring tendon autograft insufficiency allows for preoperative
      determination of additional graft source possibilities, resulting in a more
      prompt surgical strategy.

PMID- 23549313
TI  - Limb salvage and amputation in Type 3C tibial fractures.
AB  - OBJECTIVE: The aim of this study was to evaluate the results of limb salvage and
      primary amputation treatments in patients with Type 3C tibia fractures and
      compare with normative population data. METHODS: Limb salvage was performed in 20
      patients and primary amputation in 14 patients with Type 3C tibia fractures
      between 1993 and 2009. Mean follow-up period was 5.3 years. Treatment times,
      complications, number of operations and return-to-work status of groups were
      compared. The Short Form-36 (SF-36) was used to assess quality of life and
      domains were compared among the patient groups and normative data. RESULTS: Limb
      salvage patients had longer treatment periods with more operations and
      complications than the primary amputation group. Return-to-work percentage was
      59% in the limb salvage group and 71% in the amputation group. There was no
      statistical difference in all SF-36 domains for limb salvage and primary
      amputation patients. Physical functioning, social functioning, limitation due to
      emotional problems and pain were statistically lower in all patients than in the
      general population. CONCLUSION: Type 3C tibia fractures treated with both limb
      salvage and primary amputation have negative effects on quality of life. Patients
      should be informed about limited functional capacity, pain complications and
      problems with return-to-work at the end of treatment. In addition, high rates of
      limb salvage can be achieved with proper conditions in suitable patients.

PMID- 23549314
TI  - The comparison of plate-screw and tension band techniques in the osteosynthesis
      of Danis-Weber Type A and B lateral malleolar fractures.
AB  - OBJECTIVE: The aim of this study was to compare the clinical and radiological
      results of plate-screw and tension band fixation in isolated Danis-Weber Type A
      and B lateral malleolar fractures. METHODS: A total of 135 cases of lateral
      malleolar fractures (82 Danis-Weber Type B and 53 Type A) operated on in 4
      different centers and 6 orthopaedic clinics between November 2005 and December
      2010 were reviewed retrospectively. Eigthy-one patients (55 Type B and 26 Type A)
      had lateral 1/3 tubular plate and screw fixation (Group 1), while the remaining
      54 patients (27 Type B and 27 Type A) were operated on with tension band
      technique (Group 2). The clinical and radiological results of the groups were
      compared. Student t test was used in statistical analysis. RESULTS: The mean
      length of surgical incision scar was 4.9 cm (4.5-5.4 cm) for Type A fractures and
      6.8 cm (5.6-7.5 cm) for Type B in Group 1 and 4.0 cm (3.5-5.2 cm) for Type A and
      5.3 cm (5.0-5.9 cm) for Type B fractures in Group 2. Radiological union was
      obtained at mean of 10 weeks (7-13 weeks) in Group 1 and 9 weeks (7-12) in Group
      2. The implant had to be removed in 12 patients in Group 1 and in one patient in
      Group 2. The mean AOFAS Score was 90 (72-100) and 92 (70-100) in Groups 1 and 2,
      respectively. CONCLUSION: Both plate-screw and tension band techniques revealed
      excellent results in isolated Danis-Weber Type A and B fractures. The tension
      band technique may be an alternative fixation method in the treatment of these
      fractures.

PMID- 23549315
TI  - Coracoid versus lateral sagittal infraclavicular block.
AB  - OBJECTIVE: The aim of this study was to compare block performance time and
      secondarily success rates of coracoid block (CB) and lateral sagittal
      infraclavicular block (LSIB). METHODS: This prospective study included 100 adult
      patients scheduled for upper limb surgery. Patients were randomly allocated to
      receive either a CB or LSIB. A local anesthetic mixture of 20 ml of
      levobupivacaine 5 mg/ml and 20 ml of lidocaine 20 mg/ml with 5 ug/ml epinephrine
      (total 40 ml) was administered after obtaining either a median, ulnar or radial
      nerve type response. Sensory block was tested at 10-minute intervals for 40 min.
      RESULTS: Block performance time (CB Group: 5.2+/-1.9 min, LSIB Group: 5.5+/-1.4
      min) and block success rate (CB Group: 86%, LSIB Group: 92%) were similar in both
      groups. In the LSIB group, sensory block of the ulnar nerve at 10, 20 and 30
      minutes and at the radial nerve at 20 minutes was significantly more intense than
      the CB group (p<0.05). There were four vascular punctures in the LSIB group.
      CONCLUSION: Both block techniques were effective and performed in a similar time
      period.

PMID- 23549316
TI  - Acetabular index values in healthy Turkish children between 6 months and 8 years
      of age: a cross-sectional radiological study.
AB  - OBJECTIVE: The aim of this study was to determine the normal acetabular index
      values in children between 6 months and 8 years of age based on sex, age and side
      and to define the cutoff values for mild and severe acetabular dysplasia.
      METHODS: The records collected from the data pool that was gathered to define the
      prevalence of untreated congenital hip dislocation in Turkish children between 6
      months and 14 years of age was used. The acetabular index was measured on pelvic
      and abdominal radiographs of children between 6 months and 8 years of age, taken
      in 19 different cities for non-dysplasia related causes. The distribution of the
      index values based on age, sex and side. RESULTS: Thirty-three hips of 21
      children (0.75%) out of 2788 children were found to be subluxated or luxated.
      Acetabular index values of 5534 hips of 2767 children were measured. Acetabular
      index values of 723 (13%) hips of 493 children (17.8%) were found to be between 1
      and 2 standard deviations. Acetabular index values of 147 hips (2.65%) of 118
      children (4.3%) were calculated to be above 2 standard deviations. There was a
      negative correlation between the acetabular index and age. CONCLUSIONS: The study
      defines the normal acetabular index values in healthy Turkish children between 6
      months and 8 years of age and the expected acetabular index values for mild and
      severe dysplasia.

PMID- 23549309
TI  - Ghrelin: central and peripheral implications in anorexia nervosa.
AB  - Increasing clinical and therapeutic interest in the neurobiology of eating
      disorders reflects their dramatic impact on health. Chronic food restriction
      resulting in severe weight loss is a major symptom described in restrictive
      anorexia nervosa (AN) patients, and they also suffer from metabolic disturbances,
      infertility, osteopenia, and osteoporosis. Restrictive AN, mostly observed in
      young women, is the third largest cause of chronic illness in teenagers of
      industrialized countries. From a neurobiological perspective, AN-linked behaviors
      can be considered an adaptation that permits the endurance of reduced energy
      supply, involving central and/or peripheral reprograming. The severe weight loss
      observed in AN patients is accompanied by significant changes in hormones
      involved in energy balance, feeding behavior, and bone formation, all of which
      can be replicated in animals models. Increasing evidence suggests that AN could
      be an addictive behavior disorder, potentially linking defects in the reward
      mechanism with suppressed food intake, heightened physical activity, and mood
      disorder. Surprisingly, the plasma levels of ghrelin, an orexigenic hormone that
      drives food-motivated behavior, are increased. This increase in plasma ghrelin
      levels seems paradoxical in light of the restrained eating adopted by AN
      patients, and may rather result from an adaptation to the disease. The aim of
      this review is to describe the role played by ghrelin in AN focusing on its
      central vs. peripheral actions. In AN patients and in rodent AN models, chronic
      food restriction induces profound alterations in the " ghrelin " signaling that
      leads to the development of inappropriate behaviors like hyperactivity or
      addiction to food starvation and therefore a greater depletion in energy
      reserves. The question of a transient insensitivity to ghrelin and/or a potential
      metabolic reprograming is discussed in regard of new clinical treatments
      currently investigated.

PMID- 23549317
TI  - Ischial and pubic osteotomies performed by medial approach during periacetabular
      osteotomies: an anatomical study.
AB  - OBJECTIVE: The aim of this study was to identify the anatomic landmarks of
      ischial and pubic osteotomies performed as part of Bernese periacetabular
      osteotomy, measure the distances of these landmarks to the main neurovascular
      structures and determine whether these osteotomies can be performed and
      visualized using a medial approach. METHODS: The study included 20 hemipelvises
      of 10 formaldehyde-fixed cadavers. A medial surgical approach between the
      adductor longus and pectineus muscles was used, while protecting the obturator
      artery and nerve. The superior pubic ramus was subperiostally exposed to identify
      the anterior border of the anterior obturator tubercle and the projection point
      of the highest point of the obturator sulcus on the obturator crest as the two
      landmarks of pubic bone osteotomy. The line connecting the inferior border of the
      posterior obturator tubercle and the highest point of the ischial spine on the
      ischial bone was determined as the osteotomy line. Posterior dissection was
      carried out to measure the distance from the ischial osteotomy to the pudendal
      neurovascular structures. All measurements were performed using a digital
      caliper. RESULTS: The mean distance from the obturator sulcus to the obturator
      nerve was 15.3 (range: 8.1 to 30.5) mm. The mean distance from the anterior
      obturator tubercle to the obturator nerve was 34.3 (range: 27.1 to 49.5) mm and
      to the obturator artery was 38.5 (range: 29.4 to 51.1) mm. The mean distance from
      the ischial osteotomy to the pudendal neurovascular structures was 13.6 (range:
      11.2 to 17.6) mm. CONCLUSION: The "pubic osteotomy line" connecting the anterior
      obturator tubercle and obturator crest, and the inferior border of the posterior
      obturator tubercle (the starting point of the ischial osteotomy line) can be
      approached and visualized safely using a medial incision in Bernese
      periacetabular osteotomy.

PMID- 23549318
TI  - Biomechanical properties of ciprofloxacin loaded bone cement.
AB  - OBJECTIVE: The purpose of this study was to investigate the biomechanical
      properties of bone cement used in joint replacement surgery after the addition of
      ciprofloxacin. METHODS: The first group received bone cement only and served as a
      control for the 4 groups where 500 mg, 1000 mg, 1500 mg and 2000 mg of
      ciprofloxacin were added to yield 40 g of bone cement. Axial compression tests
      were conducted using a 50,000 Newton capacity tension-compression testing device.
      RESULTS: While axial compression strength at failure was 80.2+/-4.3 MPa in the
      control group, values in the ciprofloxacin-treated groups decreased with rising
      concentration of ciprofloxacin to 74.5+/-5.4 MPa, 70.6+/-4.8 MPa, 70.5+/-4.7 MPa,
      and 69.3+/-3.4 MPa. CONCLUSION: Bone cement with addition of 500 to 1500 mg
      ciprofloxacin maintained mechanical axial strength values above 70.0 MPa
      recommended by American Society for Testing and Materials and can be safely used
      in joint replacement surgery.

PMID- 23549319
TI  - A neuroblastoma case presenting with pathologic femur fracture.
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood which
      should be considered in the differential diagnosis of bone metastases and
      resultant pathological fractures, especially in children under 5 years old. We
      present an 11-month-old girl who presented with a pathological femur fracture and
      was diagnosed with metastatic neuroblastoma.

PMID- 23549320
TI  - Trigger finger at the carpal tunnel level: three case reports.
AB  - Although trigger finger occurs mostly due to a problem at the A1 pulley various
      other causes have also been reported. We present three patients with different
      tumors at the carpal tunnel as a cause of triggering. All patients were treated
      with local excision.

PMID- 23549321
TI  - Osteotendinous repair of bilateral spontaneous quadriceps tendon ruptures with
      the Krackow technique in two patients with chronic renal failure.
AB  - Although unilateral traumatic quadriceps tendon rupture is a relatively frequent
      pathology, bilateral non-traumatic spontaneous ruptures are uncommon and are
      usually associated with chronic renal failure, hyperparathyroidism, gout, and
      systemic lupus erythematosus. This paper aimed to discuss two patients with
      chronic renal failure treated with the Krackow suture technique for spontaneous
      bilateral quadriceps tendon rupture.

PMID- 23549322
TI  - Development of drug loaded nanoparticles for tumor targeting. Part 2: Enhancement
      of tumor penetration through receptor mediated transcytosis in 3D tumor models.
AB  - We report that receptor mediated transcytosis can be utilized to facilitate tumor
      penetration by drug loaded nanoparticles (NPs). We synthesized hyaluronan (HA)
      coated silica nanoparticles (SNPs) containing a highly fluorescent core to target
      CD44 expressed on the cancer cell surface. Although prior studies have primarily
      focused on CD44 mediated endocytosis to facilitate cellular uptake of HA-NPs by
      cancer cells, we discovered that, once internalized, the HA-SNPs could be
      transported out of the cells with their cargo. The exported NPs could be taken up
      by neighboring cells. This enabled the HA-SNPs to penetrate deeper inside tumors
      and reach a much greater number of tumor cells in 3D tumor models, presumably
      through tandem cycles of CD44 mediated endocytosis and exocytosis. When
      doxorubicin (DOX) was loaded onto the NPs, better penetration of multilayered
      tumor cells was observed with much improved cytotoxicities against both drug
      sensitive and drug resistant cancer spheroids compared to the free drug. Thus,
      targeting receptors such as CD44 that can readily undergo recycling between the
      cell surface and interior of the cells can become a useful strategy to enhance
      the tumor penetration potential of NPs and the efficiency of drug delivery
      through receptor mediated transcytosis.

PMID- 23549323
TI  - Neonatal marfan syndrome: report of two cases.
AB  - BACKGROUND: Neonatal Marfan syndrome is a rare and severe phenotype of this
      disease. A poor prognosis is anticipated due to the high probability of
      congestive heart failure, and mitral and tricuspid regurgitations with suboptimal
      response to medical therapy and difficulties in surgical management at an early
      age. CASE PRESENTATION: We present two consecutive patients with this disease who
      are the first reported cases from Iran to the best of our knowledge.
      Unfortunately both of them died shortly after diagnosis. CONCLUSION: Neonatal
      Marfan syndrome is reported from Iran and has a poor prognosis like the patients
      reported from elsewhere.

PMID- 23549324
TI  - The Development of a Custom Built Portable Impact Testing Device for Assessing
      the Cushioning Properties of Athletic Socks.
AB  - Despite manufacturer claims that athletic socks attenuate force during exercise,
      no device exists to assess this. Therefore, this study outlines the development
      of a custom built impact testing device for assessing the cushioning properties
      of socks. The device utilised a gravity driven impact striker (8.5 kg), released
      from 0.05 m, which impacted a no sock, sock or a basic shoe/sock condition in the
      vertical axis. A load cell (10000 Hz) assessed peak impact force, time to peak
      impact force and loading rate. Reliability was investigated between day, between
      trial and within trial. Excellent reliability (coefficient of variation < 5%
      adjusted for 95% confidence limits) was reported for peak impact force in all
      conditions, with no evidence of systematic bias. Good reliability (coefficient of
      variation < 10% adjusted for 68% confidence limits) was reported for time to peak
      impact force and loading rate with some evidence of systematic bias. It was
      concluded that the custom built impact testing device was reliable and sensitive
      for the measurement of peak impact force on socks.

PMID- 23549325
TI  - Microscopic colitis in children with chronic diarrhea.
AB  - OBJECTIVE: The aim of the present study was to study microscopic colitis (MC) in
      children with special reference to its role in chronic diarrhea and changes in
      mucosal biopsies. METHODS: A total of 100 consecutive children ages 3 to 12
      years, with nonbloody diarrhea (passage of >=3 loose stools per day) of >12
      weeks' duration were screened and 26 were enrolled in the study in which no
      specific etiology could be found and colonoscopy did not reveal any mucosal
      abnormality. Colonic biopsies were evaluated for the presence of lymphocytic
      colitis or collagenous colitis and those with the characteristic changes were
      defined to have MC (group A). Colonic biopsies from patients with MC were
      compared with biopsies from patients with chronic diarrhea but no evidence of MC
      (group B). One hundred children ages 3 to 12 years with bleeding per rectum were
      screened and colonic biopsies from 45 patients (group C) who had colonic mucosal
      changes but no vascular or polyp lesion were compared with patients with MC.
      RESULTS: Of the 26 patients with chronic diarrhea, MC was found in 5 (3
      lymphocytic colitis and 2 collagenous colitis). Significantly higher
      polymorphonuclear infiltration was seen in group A as compared with group B (13.8
      [5.4-20.6] vs 7.2 [0-19.6]; P = 0.03) or group C (13.8 [5.4-20.6] vs 4 [0-13.4];
      P = 0.007). Intraepithelial lymphocytes (12 [4-32] vs 4 [0-24]; P = 0.008) and
      basement membrane thickening (3.5 [2.9-10.6] vs 2.5 [1.6-5.86]; P = 0.008) were
      also significantly higher in group A as compared with group C. CONCLUSIONS: MC
      was found to be present in children with nonbloody chronic diarrhea in children.
      Further multicentric studies may provide adequate data on its prevalence.

PMID- 23549326
TI  - Anti-inflammatory effect of obestatin and ghrelin in dextran sulfate sodium
      induced colitis in rats.
AB  - BACKGROUND AND OBJECTIVES: Obestatin and ghrelin are hormones derived from the
      same gene but have opposing effects. Ghrelin has anti-inflammatory activities;
      however, the role of obestatin in the inflammatory processes has not been clearly
      demonstrated yet. The aim of the study was to analyse and compare the anti
      inflammatory effect of exogenous ghrelin and obestatin in a rat model of colitis.
      METHODS: Acute and chronic colitis was induced in 96 rats by adding 3% dextran
      sulfate sodium to the drinking water for 5 and 10 days, respectively.
      Intraperitoneal pretreatment with ghrelin or obestatin was started before the
      induction of colitis, and continued for 5 and 10 days. Clinical signs of the
      disease and histopathological changes were evaluated. By-products of neutrophil
      activation, lipid peroxidation, and inflammatory and anti-inflammatory cytokines
      were measured in colonic tissues. RESULTS: Obestatin and ghrelin significantly
      ameliorated clinical and histopathological severity of chronic colitis, whereas
      they were less effective in the acute form. Therapeutic effect of ghrelin and
      obestatin in acute colitis was associated with reduced lipid peroxidation and TH1
      induced inflammatory response, whereas obestatin in chronic colitis was
      protective via the suppression of polymorphonuclear leukocyte infiltration and
      enhancement of glutathione synthesis. Moreover, therapeutic effects of ghrelin
      and obestatin in chronic colitis appear to be associated with inhibition of
      inflammatory and activation of anti-inflammatory cytokines. CONCLUSIONS: This
      study demonstrated the novel anti-inflammatory effect of obestatin and ghrelin in
      an experimental model of colitis. Although both obestatin and ghrelin exerted
      anti-inflammatory effects in chronic colitis, they were less effective in acute
      colitis.

PMID- 23549327
TI  - Fecal S100A12: identifying intestinal distress in very-low-birth-weight infants.
AB  - OBJECTIVES: The aim of the study was to determine whether longitudinal
      measurements of fecal S100A12, a damage-associated molecular pattern protein,
      which is released from neutrophils or monocytes under stress, can detect very-low
      birth-weight (VLBW) infants at risk for intestinal distress apart from
      necrotizing enterocolitis. METHODS: This prospective study included 46 VLBW
      infants with intestinal distress and 49 reference patients. Meconium and stool
      samples were collected prospectively on alternate days for 4 weeks, and fecal
      S100A12 was measured by enzyme-linked immunosorbent assay. RESULTS: Gestational
      age and weight at birth were significantly lower in patients with intestinal
      distress when compared to unaffected reference infants. Median levels of fecal
      S100A12 were significantly higher in patients with intestinal distress at onset
      of disease and before compared with unaffected reference infants. Median levels
      of fecal S100A12 declined steadily to baseline levels within 2 weeks after
      disease onset. The ideal cutoff value for identifying patients with intestinal
      distress within 7 days before disease onset was 60 MUg/kg (sensitivity 0.73;
      specificity 0.55). CONCLUSIONS: Fecal S100A12 levels are increased in VLBW
      infants with intestinal distress; however, the potential for S100A12 as an early
      biomarker is largely limited by overlaps between values of infants with
      intestinal distress and the reference population.

PMID- 23549328
TI  - Advances in multiplex PCR: balancing primer efficiencies and improving detection
      success.
AB  - 1. Multiplex PCR is a valuable tool in many biological studies but it is a
      multifaceted procedure that has to be planned and optimised thoroughly to achieve
      robust and meaningful results. In particular, primer concentrations have to be
      adjusted to assure an even amplification of all targeted DNA fragments. Until
      now, total DNA extracts were used for balancing primer efficiencies; however, the
      applicability for comparisons between taxa or different multiple-copy genes was
      limited owing to the unknown number of template molecules present per total DNA.
      2. Based on a multiplex system developed to track trophic interactions in high
      Alpine arthropods, we demonstrate a fast and easy way of generating standardised
      DNA templates. These were then used to balance the amplification success for the
      different targets and to subsequently determine the sensitivity of each primer
      pair in the multiplex PCR. 3. In the current multiplex assay, this approach led
      to an even amplification success for all seven targeted DNA fragments. Using this
      balanced multiplex PCR, methodological bias owing to variation in primer
      efficiency will be avoided when analysing field-derived samples. 4. The approach
      outlined here allows comparing multiplex PCR sensitivity, independent of the
      investigated species, genome size or the targeted genes. The application of
      standardised DNA templates not only makes it possible to optimise primer
      efficiency within a given multiplex PCR, but it also offers to adjust and/or to
      compare the sensitivity between different assays. Along with other factors that
      influence the success of multiplex reactions, and which we discuss here in
      relation to the presented detection system, the adoption of this approach will
      allow for direct comparison of multiplex PCR data between systems and studies,
      enhancing the utility of this assay type.

PMID- 23549329
TI  - Expanding awareness of docosahexaenoic acid during pregnancy.
AB  - Pregnant women do not currently meet the consensus recommendation for
      docosahexaenoic acid (DHA) (>=200 mg/day). Pregnant women in Australia are not
      receiving information on the importance of DHA during pregnancy. DHA pregnancy
      education materials were developed using current scientific literature, and
      tested for readability and design aesthetics. The study aimed to evaluate their
      usefulness, the desire for pregnant women to receive these materials and whether
      a larger separate study (using a control group) is warranted to evaluate the
      influence the materials may have on increasing DHA consumption in pregnant women
      in Australia. Pregnant women (N = 118) were recruited at antenatal clinics at two
      NSW hospitals. Participants completed a 16-item questionnaire and DHA educational
      materials (pamphlet and shopping card) were provided. Participants were contacted
      via phone two weeks later and completed the second questionnaire (25-item, N =
      74). Statistics were conducted in SPSS and qualitative data were analysed to
      identify common themes. Ninety three percent of women found the materials useful,
      with the main reason being it expanded their knowledge of DHA food sources. Only
      34% of women had received prior information on DHA, yet 68% said they would like
      to receive information. Due to the small sample size and lack of a control group,
      this small study cannot provide a cause and effect relationship between the
      materials and nutrition related behaviours or knowledge, however the results
      indicate a potential positive influence towards increased fish consumption and
      awareness of DHA containing foods. This suggests a larger study, with a control
      group is warranted to identify the impact such materials could have on Australian
      pregnant women.

PMID- 23549330
TI  - Use of dietary supplements in patients seeking treatment at a periodontal clinic.
AB  - Dietary supplement use may modify the risk of periodontal disease but effects on
      wound healing after periodontal procedures are less clear. This study
      characterized dietary supplement use by male and female patients (n = 376)
      attending a periodontal clinic-information that is essential for evidence-based
      intervention studies that may improve patient outcomes after periodontal
      procedures. Calcium, vitamin D, multivitamin and vitamin C were most commonly
      used. A greater (p <= 0.05) number of males took no supplements compared to
      females, and more (p <= 0.05) females than males took >= four supplements.
      Females took more (p <= 0.05) calcium, vitamin D, fish oil, green tea, magnesium,
      omega 3,6,9 and B vitamin complex. Younger patients (31-50 years) had the highest
      (p <= 0.05) frequency of no supplement use compared to older age groups. Patients
      over age 50 had a higher (p <= 0.05) frequency of using >= four supplements
      including calcium and vitamin D. Supplement use was lower (p <= 0.05) in smokers,
      particularly for calcium, fish oil, green tea and vitamin D. In conclusion,
      females, older individuals and non-smokers have higher supplement use. Future
      dietary intervention studies can focus on supplements with known biological
      activities-anti-inflammatory, antioxidant or osteogenic activity-that may enhance
      wound healing after reconstructive periodontal procedures.

PMID- 23549332
TI  - Shorthand notation for lipid structures derived from mass spectrometry.
AB  - There is a need for a standardized, practical annotation for structures of lipid
      species derived from mass spectrometric approaches; i.e., for high-throughput
      data obtained from instruments operating in either high- or low-resolution modes.
      This proposal is based on common, officially accepted terms and builds upon the
      LIPID MAPS terminology. It aims to add defined levels of information below the
      LIPID MAPS nomenclature, as detailed chemical structures, including
      stereochemistry, are usually not automatically provided by mass spectrometric
      analysis. To this end, rules for lipid species annotation were developed that
      reflect the structural information derived from the analysis. For example,
      commonly used head group-specific analysis of glycerophospholipids (GP) by low
      resolution instruments is neither capable of differentiating the fatty acids
      linked to the glycerol backbone nor able to define their bond type (ester, alkyl
      , or alk-1-enyl-ether). This and other missing structural information is covered
      by the proposed shorthand notation presented here. Beyond GPs, we provide
      shorthand notation for fatty acids/acyls (FA), glycerolipids (GL), sphingolipids
      (SP), and sterols (ST). In summary, this defined shorthand nomenclature provides
      a standard methodology for reporting lipid species from mass spectrometric
      analysis and for constructing databases.

PMID- 23549336
TI  - Patterns of population genetic variation in sympatric chiltoniid amphipods within
      a calcrete aquifer reveal a dynamic subterranean environment.
AB  - Calcrete aquifers from the Yilgarn region of arid central Western Australia
      contain an assemblage of obligate groundwater invertebrate species that are each
      endemic to single aquifers. Fine-scale phylogeographic and population genetic
      analyses of three sympatric and independently derived species of amphipod
      (Chiltoniidae) were carried out to determine whether there were common patterns
      of population genetic structure or evidence for past geographic isolation of
      populations within a single calcrete aquifer. Genetic diversity in amphipod
      mitochondrial DNA (cytochrome c oxidase subunit I gene) and allozymes were
      examined across a 3.5 km(2) region of the Sturt Meadows calcrete, which contains
      a grid of 115 bore holes (=wells). Stygobiont amphipods were found to have high
      levels of mitochondrial haplotype diversity coupled with low nucleotide
      diversity. Mitochondrial phylogeographic structuring was found between
      haplogroups for one of the chiltoniid species, which also showed population
      structuring for nuclear markers. Signatures of population expansion in two of the
      three species, match previous findings for diving beetles at the same site,
      indicating that the system is dynamic. We propose isolation of populations in
      refugia within the calcrete, followed by expansion events, as the most likely
      source of intraspecific genetic diversity, due to changes in water level
      influencing gene flow across the calcrete.

PMID- 23549331
TI  - A distal enhancer controls cytokine-dependent human cPLA2alpha gene expression.
AB  - Specific control of group IVA cytosolic phospholipase A2 (cPLA2alpha or PLA2G4A)
      expression modulates arachidonic acid production, thus tightly regulating the
      downstream effects of pro- and anti-inflammatory eicosanoids. The significance of
      this pathway in human disease is apparent in a range of pathologies from
      inflammation to tumorigenesis. While much of the regulation of cPLA2alpha has
      focused on posttranslational phosphorylation of the protein, studies on
      transcriptional regulation of this gene have focused only on proximal promoter
      regions. We have identified a DNase I hypersensitive site encompassing a 5'
      distal enhancer element containing a highly conserved consensus AP-1 site
      involved in transcriptional activation of cPLA2alpha by interleukin (IL)-1beta.
      Chromatin immunoprecipitation (ChIP), knockdown, knockout, and overexpression
      analyses have shown that c-Jun acts both in a negative and positive regulatory
      role. Transcriptional activation of cPLA2alpha occurs through the phosphorylation
      of c-Jun in conjunction with increased association of C/EBPbeta with the distal
      novel enhancer. The association of C/EBPbeta with the transcriptional activation
      complex does not require an obvious DNA binding site. These data provide new and
      important contributions to the understanding of cPLA2alpha regulation at the
      transcriptional level, with implications for eicosanoid metabolism, cellular
      signaling, and disease pathogenesis.

PMID- 23549337
TI  - The discovery of Foxl2 paralogs in chondrichthyan, coelacanth and tetrapod
      genomes reveals an ancient duplication in vertebrates.
AB  - The Foxl2 (forkhead box L2) gene is an important member of the forkhead domain
      family, primarily responsible for the development of ovaries during female sex
      differentiation. The evolutionary studies conducted previously considered the
      presence of paralog Foxl2 copies only in teleosts. However, to search for
      possible paralog copies in other groups of vertebrates and ensure that all
      predicted copies were homolog to the Foxl2 gene, a broad evolutionary analysis
      was performed, based on the forkhead domain family. A total of 2464 sequences for
      the forkhead domain were recovered, and subsequently, 64 representative sequences
      for Foxl2 were used in the evolutionary analysis of this gene. The most important
      contribution of this study was the discovery of a new subgroup of Foxl2 copies
      (ortholog to Foxl2B) present in the chondrichthyan Callorhinchus milii, in the
      coelacanth Latimeria chalumnae, in the avian Taeniopygia guttata and in the
      marsupial Monodelphis domestica. This new scenario indicates a gene duplication
      event in an ancestor of gnathostomes. Furthermore, based on the analysis of the
      syntenic regions of both Foxl2 copies, the duplication event was not exclusive to
      Foxl2. Moreover, the duplicated copy distribution was shown to be complex across
      vertebrates, especially in tetrapods, and the results strongly support a loss of
      this copy in eutherian species. Finally, the scenario observed in this study
      suggests an update for Foxl2 gene nomenclature, extending the actual suggested
      teleost naming of Foxl2A and Foxl2B to all vertebrate sequences and contributing
      to the establishment of a new evolutionary context for the Foxl2 gene.

PMID- 23549338
TI  - Toward genomic prediction from whole-genome sequence data: impact of sequencing
      design on genotype imputation and accuracy of predictions.
AB  - Genomic prediction from whole-genome sequence data is attractive, as the accuracy
      of genomic prediction is no longer bounded by extent of linkage disequilibrium
      between DNA markers and causal mutations affecting the trait, given the causal
      mutations are in the data set. A cost-effective strategy could be to sequence a
      small proportion of the population, and impute sequence data to the rest of the
      reference population. Here, we describe strategies for selecting individuals for
      sequencing, based on either pedigree relationships or haplotype diversity.
      Performance of these strategies (number of variants detected and accuracy of
      imputation) were evaluated in sequence data simulated through a real Belgian Blue
      cattle pedigree. A strategy (AHAP), which selected a subset of individuals for
      sequencing that maximized the number of unique haplotypes (from single-nucleotide
      polymorphism panel data) sequenced gave good performance across a range of
      variant minor allele frequencies. We then investigated the optimum number of
      individuals to sequence by fold coverage given a maximum total sequencing effort.
      At 600 total fold coverage (x 600), the optimum strategy was to sequence 75
      individuals at eightfold coverage. Finally, we investigated the accuracy of
      genomic predictions that could be achieved. The advantage of using imputed
      sequence data compared with dense SNP array genotypes was highly dependent on the
      allele frequency spectrum of the causative mutations affecting the trait. When
      this followed a neutral distribution, the advantage of the imputed sequence data
      was small; however, when the causal mutations all had low minor allele
      frequencies, using the sequence data improved the accuracy of genomic prediction
      by up to 30%. 

PMID- 23549339
TI  - Characteristics of the transformation frequency at the tumor promotion stage of
      airborne particulate and gaseous matter at ten sites in Japan.
AB  - We used a high-volume air sampler in the summer of 2007 and the winter of 2008 at
      ten Japanese sites (Sapporo, Sendai, Maebashi, Tsukuba, Shinjuku, Sagamihara,
      Shizuoka, Touhaku, Kitakyushu, and Kagoshima) to collect total suspended
      particulate (TSP) and gaseous matter for evaluation. We evaluated the
      transformation frequency at the tumor promotion stage of these samples in a cell
      transformation assay using Bhas 42 cells, which were established from BALB/c 3T3
      cells transfected with the v-Ha-ras oncogene. All samples collected from the
      gaseous matter were negative for transformed foci. There were several patterns of
      transformation frequency at the tumor promotion stage by area for the TSP
      samples. At Sapporo, the transformation frequency at the tumor promotion stage
      was remarkably higher in winter than in summer as well as in winter at the other
      sites. At six urban cities from Sendai to Shizuoka, the levels of transformed
      frequencies per MUg of suspended particulates in winter were almost the same, and
      were higher than those of the remaining three sites. At three sites, Touhaku,
      Kitakyushu and Kagoshima, the transformation results in winter were judged as
      negative. The characteristics of the transformed frequencies of the compounds
      adsorbed on particulate matter at the sampling sites were significant in winter.
      We also studied the correlation between the transformation frequency at the tumor
      promotion stage of the TSP samples and the results of quantitative analysis of 16
      polyaromatic hydrocarbons (PAHs) at the ten sites. We found that the
      transformation frequency at the tumor promotion stage of airborne samples could
      not be predicted based on the quantitative results of the PAHs in those samples.
      These data suggest that direct risk assessment of air samples with a bioassay is
      more valuable than quantitative analysis of compounds such as PAHs for predicting
      carcinogenicity.

PMID- 23549340
TI  - Age- and activity-related differences in the mechanisms underlying maximal power
      production in young and older adults.
AB  - The purpose of this study was to examine the interactions between aging, activity
      levels and maximal power production during cycling. Participants were divided
      into younger adults (YA), older active adults (OA,) and older sedentary adults
      (OS). Absolute maximum power was significantly greater in YA compared with OS and
      OA; no differences were found between OA and OS. The age-related difference in
      maximum power was accompanied by greater absolute peak knee extension and knee
      flexion powers. Relative joint power contributions revealed both age- and
      activity-related differences. YA produced less relative hip extension power than
      older adults, regardless of activity level. The OS participants produced less
      relative knee flexion power than active adults, regardless of age. The results
      show the age-related decline in muscular power production is joint specific and
      that activity level can be a modifier of intersegmental coordination, which has
      implications for designing interventions for the aging population. 

PMID- 23549341
TI  - The closed wedge counter shift osteotomy for the correction of post-traumatic
      cubitus varus.
AB  - A variety of osteotomies have been proposed to correct post-traumatic cubitus
      varus deformity. Each one of them has advantages and disadvantages or
      limitations. A new technique for correcting post-traumatic cubitus varus with
      closed wedge counter shift osteotomy of the distal humerus is described and the
      preliminary results in six cases are reported. Five patients showed excellent
      results and one patient showed good result. We believe that the described
      technique is an alternative to the other procedures for the treatment of post
      traumatic cubitus varus with minimal internal rotation and hyperextension
      deformities. It has the advantages of being a simple, safe, inherently stable,
      technically sound procedure, and yields an excellent cosmetic outcome.

PMID- 23549342
TI  - Management of gastro-oesophageal reflux disease symptoms that do not respond to
      proton pump inhibitors.
AB  - PURPOSE OF REVIEW: Treatment-refractory gastro-oesophageal reflux disease (GERD)
      remains a significant problem in the gastroenterology clinic. In recent years,
      several studies have investigated the assessment and treatment of refractory
      GERD. RECENT FINDINGS: Patients presenting with 'refractory GERD' in fact
      represent a quite heterogeneous group consisting of those with ongoing reflux
      related symptoms and those with reflux-unrelated problems such as functional
      heartburn, dyspepsia or even eosinophilic oesophagitis. The greatest symptom
      indicators of persistent true reflux are retrosternal burning and acid taste in
      the mouth alone. Combined pH-impedance studies allow detection of reflux
      regardless of pH, and weakly acidic reflux has been suggested as a mechanism of
      residual symptoms in some patients. The use of reflux-symptom association
      calculations may help to determine the symptom causation, but refinement and
      outcome studies are needed. New treatments of refractory GERD have been
      disappointing. Surgery remains an option in very carefully selected patients, but
      again better outcome studies are required. SUMMARY: Careful history and
      investigation is required in the assessment of the proton pump inhibitor (PPI)
      refractory patient. Care to exclude alternative diagnoses is needed, and to
      phenotype those with reflux-related symptoms. Optimization of PPI therapy may
      help, as may surgery in selected patients.

PMID- 23549343
TI  - Germline excision of transgenes in Aedes aegypti by homing endonucleases.
AB  - Aedes (Ae.) aegypti is the primary vector for dengue viruses (serotypes1-4) and
      chikungunya virus. Homing endonucleases (HEs) are ancient selfish elements that
      catalyze double-stranded DNA breaks (DSB) in a highly specific manner. In this
      report, we show that the HEs Y2-I-AniI, I-CreI and I-SceI are all capable of
      catalyzing the excision of genomic segments from the Ae. aegypti genome in a
      heritable manner. Y2-I-AniI demonstrated the highest efficiency at two
      independent genomic targets, with 20-40% of Y2-I-AniI-treated individuals
      producing offspring that had lost the target transgene. HE-induced DSBs were
      found to be repaired via the single-strand annealing (SSA) and non-homologous end
      joining (NHEJ) pathways in a manner dependent on the availability of direct
      repeat sequences in the transgene. These results support the development of HE
      based gene editing and gene drive strategies in Ae. aegypti, and confirm the
      utility of HEs in the manipulation and modification of transgenes in this
      important vector.

PMID- 23549344
TI  - High mobility group box1 (HMGB1) in relation to cutaneous inflammation in
      systemic lupus erythematosus (SLE).
AB  - SUMMARY: Photosensitivity is characteristic of systemic lupus erythematosus
      (SLE). Upon ultraviolet B (UVB) exposure, patients develop inflammatory skin
      lesions in the vicinity of sunburn cells (SBCs). High mobility group box 1
      (HMGB1) is released from apoptotic and activated cells and exerts inflammatory
      actions through ligation to its receptors. METHODS: Eleven SLE patients and 10
      healthy controls (HCs) were exposed to UVB. Skin biopsies were taken before and
      at one, three and 10 days after irradiation. Sections were stained for SBC,
      HMGB1, CD3, CD68, interferon-induced protein MxA and cleaved caspase 3. In vitro
      experiments with UVB-irradiated keratinocytes were also performed. Higher numbers
      of cells that had released HMGB1 were seen in the skin of SLE patients compared
      to HCs before and after irradiation. HMGB1-negative nuclei correlated with the
      presence of SBCs, and with the number of cleaved caspase 3 positive cells in
      lupus skin. RESULTS: HMGB1 release is increased in the skin of SLE patients
      compared to HCs. Upon UVB exposure, HMGB1 release further increases in SLE
      patients and is related to the number of apoptotic cells. Our data suggest that
      HMGB1, probably released from apoptotic keratinocytes, contributes to the
      development of inflammatory lesions in the skin of SLE patients upon UVB
      exposure.

PMID- 23549345
TI  - Evaluation of genetically modified sugarcane lines carrying Cry 1AC gene using
      molecular marker techniques.
AB  - Five genetically modified insect resistant sugarcane lines harboring the Bt Cry
      1AC gene to produce insecticidal proteins were compared with non-transgenic
      control by using three types of molecular marker techniques namely, RAPD, ISSR
      and AFLP. These techniques were applied on transgenic and non-transgenic plants
      to investigate the genetic variations, which may appear in sugarcane clones. This
      variation might demonstrate the genomic changes associated with the
      transformation process, which could change important molecular basis of various
      biological phenomena. Genetic variations were screened using 22 different RAPD
      primers, 10 ISSR primers and 13 AFLP primer combinations. Analysis of RAPD and
      ISSR banding patterns gave no exclusive evidence for genetic variations.
      Meanwhile, the percentage of polymorphic bands was 0.45% in each of RAPD and
      ISSR, while the polymorphism generated by AFLP analysis was 1.8%. The maximum
      percentage of polymorphic bands was 1.4%, 1.1% and 5.5% in RAPD, ISSR and AFLP,
      respectively. These results demonstrate that most transgenic lines showed genomic
      homogeneity and verified minor genomic changes. Dendrograms revealing the
      relationships among the transgenic and control plants were developed from the
      data of each of the three marker types.

PMID- 23549346
TI  - A highly efficient access to enantiopure tetrahydropyridines: dual-organocatalyst
      promoted asymmetric cascade reaction.
AB  - A highly efficient cascade process of Michael-aza-Henry-hemiaminalization
      dehydration was established for the construction of enantiopure
      tetrahydropyridines using the combination of prolinol trimethylsilyl ether and
      cinchona alkaloid catalysts. This new approach allowed for the application of
      aliphatic imines, generated in situ from aldehydes and amines. Good yields (up to
      90%), high enantio- (up to >99% ee) and diastereoselectivities (>99 : 1 d.r. in
      all cases) were achieved for a broad spectrum of substrates under mild
      conditions.

PMID- 23549347
TI  - Effect of growth hormones on some antioxidant parameters and gene expression in
      tomato.
AB  - Bioregulators have a great effect on vital processes of plant growth and
      development. Known plant bioregulators include Naphthalene acetic acid (NAA),
      Indole-3-butyric acid (IBA) and Indole-3-acetic acid (IAA). Natural or synthetic
      plant bioregulators are organic compounds that affect the physiological processes
      in the plant, either to control some of these processes or to modify them. For
      example these bioregulators can affect the nature of the process, either by
      accelerating or decelerating plant growth, rates of maturation and also by
      altering the behavior of the plants or their products. Also, enhancement of
      important nutrients in human diet could be achieved by bioregulators.   This
      study uses the model crop plant Tomato (Lycopersicon esculentum). Tomato is
      affected by a group of bioregulators, this group contains compounds which are
      powerful antioxidants in vitro. The current study aims to find out the effect of
      some plant bioregulators (IAA, IBA and NAA) on tomato growth, total protein
      content and enzyme activities of ascorbate peroxidase (APX), superoxide dismutase
      (SOD) and catalase (CAT). This study also investigates the effect of the above
      mentioned bioregulators on the level of RNA expression for SOD, CAT and TPX1
      genes. The analytical quantification of target gene expression showed the induced
      effect of NAA on SOD expression and reducing effect of the other bioregulators
      (IAA and IBA) on CAT and TPX1 expression. However, at the protein level, we found
      that IBA and IAA caused a minor effect on total protein content while a
      significant effect was recorded on the total protein level using NAA. Upon
      measuring the enzyme activity of ascorbate peroxidase and catalase, we found that
      both the exogenous NAA and IBA stimulated ascorbate peroxidase activity in tomato
      while there was no considerable difference detected in IAA treated plants. Also,
      there was no considerable difference detected in catalase activity of all
      bioregulator-treated plants compared with the control.

PMID- 23549348
TI  - Photoinduced energy and charge transfer in a p-phenylene-linked dyad of boron
      dipyrromethene and monostyryl boron dipyrromethene.
AB  - Boron dipyrromethenes (BDPs) are excellent building blocks for design of
      artificial light harvesting and charge separation systems. In the present work,
      we report the results of photophysical studies of a novel dyad, in which a BDP
      and a mono-styryl BDP (MSBDP) are covalently linked to each other at the meso
      position via a p-phenylene unit. It was found that the photophysical properties
      of the dyad dissolved in polar as well as nonpolar solvents are strongly affected
      by two different types of interactions between the BDP and MSBDP parts, namely
      excitation energy transfer and photoinduced electron transfer. The first process
      delivers the excitation energy to the first excited singlet state of the MSBDP
      part upon excitation of the BDP unit. The direct or indirect (via excitation
      energy transfer) population of the first excited singlet state of the MSBDP
      moiety is followed by hole transfer to generate the charge-separated state. In
      non-polar toluene, the probability of charge separation is low, whereas in polar
      acetonitrile the charge separation quantum yield is close to unity, resulting in
      strong quenching of the MSBDP fluorescence.

PMID- 23549349
TI  - The global income and production effects of genetically modified (GM) crops 1996
      2011.
AB  - A key part of any assessment of the global value of crop biotechnology in
      agriculture is an examination of its economic impact at the farm level. This
      paper follows earlier annual studies which examined economic impacts on yields,
      key costs of production, direct farm income and effects and impacts on the
      production base of the four main crops of soybeans, corn, cotton and canola. The
      commercialization of genetically modified (GM) crops has continued to occur at a
      rapid rate, with important changes in both the overall level of adoption and
      impact occurring in 2011. This annual updated analysis shows that there have been
      very significant net economic benefits at the farm level amounting to $19.8
      billion in 2011 and $98.2 billion for the 16 year period (in nominal terms). The
      majority (51.2%) of these gains went to farmers in developing countries. GM
      technology have also made important contributions to increasing global production
      levels of the four main crops, having added 110 million tonnes and 195 million
      tonnes respectively, to the global production of soybeans and maize since the
      introduction of the technology in the mid-1990s.

PMID- 23549350
TI  - Roles of the superoxide dismutase SodB and the catalase KatA in the antibiotic
      resistance of Campylobacter jejuni.

PMID- 23549351
TI  - Artesunate has its enhancement on antibacterial activity of beta-lactams via
      increasing the antibiotic accumulation within methicillin-resistant
      Staphylococcus aureus (MRSA).
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has now emerged as a
      predominant and serious pathogen because of its resistance to a large group of
      antibiotics, leading to high morbidity and mortality. Therefore, to develop new
      agents against resistance is urgently required. Previously, artesunate (AS) was
      found to enhance the antibacterial effect of beta-lactams against MRSA. In this
      study, AS was first found to increase the accumulation of antibiotics
      (daunorubicin and oxacillin) within MRSA by laser confocal microscopy and liquid
      chromatography-tandem MS method, suggesting the increased antibiotics
      accumulation might be related to the enhancement of AS on antibiotics.
      Furthermore, AS was found not to destroy the cell structure of MRSA by
      transmission electron microscope. AS was found to inhibit gene expressions of
      important efflux pumps such as NorA, NorB and NorC, but not MepA, SepA and MdeA.
      In conclusion, our results showed that AS was capable of enhancing the
      antibacterial activity of beta-lactams via increasing antibiotic accumulations
      within MRSA through inhibiting gene expressions of efflux pumps such as NorA,
      NorB and NorC, but did not destroy the cell structure of MRSA. AS could be
      further investigated as a candidate drug for treatment of MRSA infection. 

PMID- 23549352
TI  - Lorneic acids C and D, new trialkyl-substituted aromatic acids isolated from a
      terrestrial Streptomyces sp.

PMID- 23549353
TI  - Farnesol induces cell detachment from established S. epidermidis biofilms.
AB  - Antibiotic resistance is a serious problem in Staphylococcus epidermidis
      infections as many clinical isolates of this organism are resistant to up to
      eight different antibiotics. The increased resistance to conventional antibiotic
      therapy has lead to the search for new antimicrobial therapeutic agents.
      Farnesol, an essential oil found in many plants, has been shown to be active
      against S. epidermidis. Using a type control strain we recently described that
      although farnesol was not efficient at killing biofilm bacteria, a strong
      reduction on biofilm biomass was detected, and we hypothesize that farnesol
      could, somehow, induce biofilm detachment. In this report, to test our hypothesis
      we used 36 representative clinical strains of S. epidermidis from different
      geographic locations and characterized them in terms of genetic variability by
      multilocus sequence typing and staphylococcal chromosome cassette mec. Strains
      were tested for biofilm formation, and the presence of ica, bhp and aap genes was
      determined. Stronger biofilms had always the presence of ica operon but often co
      harbored bhp and aap genes. Farnesol was then used in biofilm-forming strains,
      and biofilm detachment was detected in half of the strains tested. Furthermore,
      we also showed that farnesol inability to kill biofilm bacteria was not the
      result of the biofilm structure but was related to high cell density. Our results
      demonstrate, for the first time, that the biomass reduction previously found by
      us, and many other groups, is the result not of cell killing but instead is the
      result of biofilm detachment.

PMID- 23549354
TI  - 03219A, a new Delta(8,9)-pregnene isolated from Streptomyces sp. SCSIO 03219
      obtained from a South China Sea sediment.
AB  - 03219A (1), a new pregnene steroid possessing a rare Delta(8,9)-double bond in
      the skeleton, together with the known naphthoquinone antibiotic (+)-cryptosporin
      (2) have been isolated from the fermentation broth of Streptomyces sp. SCSIO
      03219, which was isolated from a marine sediment collected in the South China
      Sea. The structure of 03219A was elucidated using a combination of NMR, MS and X
      ray crystallographic methods. 

PMID- 23549355
TI  - Saccharosporones A, B and C, cytotoxic antimalarial angucyclinones from
      Saccharopolyspora sp. BCC 21906.
AB  - Three new angucyclinones, saccharosporones A, B and C, together with (+)
      ochromycinone, (+)-rubiginone B2, tetrangulol methyl ether and fujianmycin A,
      were obtained from fermentation of the terrestrial actinomycete of the genus
      Saccharopolyspora BCC 21906 isolated from a soil collected in Chanthaburi
      Province, Thailand. Structures of the new compounds and their relative
      configurations were assigned by NMR spectral data interpretation.
      Saccharosporones A and B exhibited antimalarial activity against Plasmodium
      falciparum K1 with IC50 values of 4.1 and 3.9 MUM. Both metabolites also
      possessed cytotoxic activities against cancer cell lines (KB, MCF-7 and NCI-H187)
      and nonmalignant Vero cell, while saccharosporone C only showed cytotoxic
      activity against NCI-H187. 

PMID- 23549356
TI  - Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular
      and antibacterial agents.
AB  - The natural product engelhardione is an underexplored chemotype for developing
      novel treatments for bacterial infections; we therefore explored this natural
      product scaffold for chemical diversification and structure-activity relationship
      studies. Macrocyclic engelhardione and structural regioisomers were synthesized
      using a series of aldol condensations and selective hydrogenations to generate
      the 1,7-diarylheptan-3-one derivatives, followed by microwave-assisted
      intramolecular Ullmann coupling to afford a series of macrocyclic diaryl ether
      analogs. An extended macrocyclic chemical library was then produced by oxime
      formation, reductive amination and O-alkylation. Antibacterial evaluation
      revealed that the reductive amination derivatives 7b and 7d showed moderate
      activities (minimum inhibitory concentrations: 12.5-25 MUg ml(-1)) against
      Mycobacterium tuberculosis and Gram-positive pathogens, as well as anti-Gram
      negative activity against an efflux impaired Escherichia coli strain. These
      results provide validated leads for further optimization and development. 

PMID- 23549357
TI  - Quality of life and emotional change for middle-aged and elderly patients with
      diabetic retinopathy.
AB  - AIM: To evaluate the SF-36, Diabetes Specificity Quality of Life Scale (DSQL) and
      anxiety and depression symptoms and investigate its changes in proliferative
      diabetic retinopathy (PDR) by vitrectomy interventions. METHODS: The present
      study included 108 diabetic retinopathy (DR) patients: 54 with PDR and 54 with
      non-proliferative diabetic retinopathy (NPDR). Each healthy control group (n=54)
      sociodemographically matched to DR groups was established respectively. The
      quality of life, anxiety and depression symptoms were evaluated and analyzed on
      preoperative and postoperative month 1 using SF-36, DSQL and Hospital Anxiety and
      Depression Scale (HADS). RESULTS: DR patients described impaired HRQL (Health
      Related Quality of life, SF-36) in 6 out of 8 subscales, including 'Body Health',
      'Body Role Function', 'General Health', 'Society Function', 'Emotion Role
      Function' and 'Mental Health'. Compared with controls, DR patients (NPDR and PDR)
      suffered from statistically significantly impaired HRQL (SF-36 Summary score)
      (P<0.05). By surgical intervention, the anxiety and depression score were
      significantly reduced, while the health and quality of life (SF-36 Summary scores
      and DSQL scores) was improved in patients with PDR (P<0.05). CONCLUSION: DR
      patients were affected in mentation and quality of life. Surgery interventions
      can improve SF-36, DSQL, anxiety and depression in PDR patients.

PMID- 23549358
TI  - Side view thrombosis microfluidic device with controllable wall shear rate and
      transthrombus pressure gradient.
AB  - Hemodynamic conditions vary throughout the vasculature, creating diverse
      environments in which platelets must respond. To stop bleeding, a growing
      platelet deposit must be assembled in the presence of fluid wall shear stress
      (tauw) and a transthrombus pressure gradient (DeltaP) that drives bleeding. We
      designed a microfluidic device capable of pulsing a fluorescent solute through a
      developing thrombus forming on collagen +/- tissue factor (TF), while
      independently controlling DeltaP and tauw. Computer control allowed step changes
      in DeltaP with a rapid response time of 0.26 mm Hg s(-1) at either venous (5.2
      dynes cm(-2)) or arterial (33.9 dynes cm(-2)) wall shear stresses. Side view
      visualization of thrombosis with transthrombus permeation allowed for
      quantification of clot structure, height, and composition at various DeltaP. Clot
      height was reduced 20% on collagen/TF and 28% on collagen alone when DeltaP was
      increased from 20.8 to 23.4 mm Hg at constant arterial shear stress. When
      visualized with a platelet-targeting thrombin sensor, intrathrombus thrombin
      levels decreased by 62% as DeltaP was increased from 0 to 23.4 mm Hg across the
      thrombus-collagen/TF barrier, consistent with convective removal of thrombogenic
      solutes due to pressure-driven permeation. Independent of DeltaP, the platelet
      deposit on collagen had a permeability of 5.45 * 10(-14) cm(2), while the
      platelet/fibrin thrombus on collagen/TF had a permeability of 2.71 * 10(-14)
      cm(2) (comparable to that of an intact endothelium). This microfluidic design
      allows investigation of the coupled processes of platelet deposition and
      thrombin/fibrin generation in the presence of controlled transthrombus permeation
      and wall shear stress.

PMID- 23549361
TI  - Camera sensor arrangement for crop/weed detection accuracy in agronomic images.
AB  - In Precision Agriculture, images coming from camera-based sensors are commonly
      used for weed identification and crop line detection, either to apply specific
      treatments or for vehicle guidance purposes. Accuracy of identification and
      detection is an important issue to be addressed in image processing. There are
      two main types of parameters affecting the accuracy of the images, namely: (a)
      extrinsic, related to the sensor's positioning in the tractor; (b) intrinsic,
      related to the sensor specifications, such as CCD resolution, focal length or
      iris aperture, among others. Moreover, in agricultural applications, the
      uncontrolled illumination, existing in outdoor environments, is also an important
      factor affecting the image accuracy. This paper is exclusively focused on two
      main issues, always with the goal to achieve the highest image accuracy in
      Precision Agriculture applications, making the following two main contributions:
      (a) camera sensor arrangement, to adjust extrinsic parameters and (b) design of
      strategies for controlling the adverse illumination effects.

PMID- 23549360
TI  - Projected changes in clear-sky erythemal and vitamin D effective UV doses for
      Europe over the period 2006 to 2100.
AB  - The benefits and the harmful effects of solar ultraviolet radiation (UVR)
      exposure have been well discussed. Most studies show concern for the solar
      overexposure in the tropics and low latitude sites and its scarcity at higher
      latitudes. Both cases are of concern, the first for diseases such as skin cancer
      and the second for the lack of vitamin D production in the skin. In this study,
      we evaluate the influence of climate change scenarios on the total ozone content
      (TOC) and typical aerosol properties, such as the optical depth (AOD) and single
      scattering albedo (SSA), over Europe. From these parameters, we estimate the
      erythemal and the vitamin D effective UVR doses from 2006 to 2100. Our results
      indicate a small reduction of the UVR daily doses caused by the ozone layer
      recovery and partially compensated by an AOD diminution through this century. The
      attenuation will be larger at high latitudes, during the springtime and for more
      polluted scenarios during this century. However, this diminution should not be
      sufficient to provide a protection condition for erythema. On the other hand, at
      higher latitudes, it possibly contributes to a relevant increase in the exposure
      time necessary for the synthesis of vitamin D, mainly during autumn and spring
      seasons.

PMID- 23549362
TI  - A solid-contact ion selective electrode for copper(II) using a succinimide
      derivative as ionophore.
AB  - All-solid-state sensors with polyvinyl chloride (PVC)-based membranes using off
      the-shelf N-hydroxysuccinimide (NHS) and succinimide (Succ) ionophores were
      prepared using DOP (dioctyl phthalate) and NPOE (ortho-nitrophenyloctyl ether) as
      plasticizers. Good responses were obtained when NHS was used. The potentiometric
      response of the proposed electrode is independent of pH over the range 2-6. The
      electrode shows a fast response time of 0.25 s. The electrode exhibits a Super
      Nernstian response, with 37.5 mV/decade, with a potentiometric detection limit of
      4.4 uM. The proposed sensor revealed good selectivity towards a group of
      transition metal ions.

PMID- 23549363
TI  - A novel flexible room temperature ethanol gas sensor based on SnO2 doped poly
      diallyldimethylammonium chloride.
AB  - A novel flexible room temperature ethanol gas sensor was fabricated and
      demonstrated in this paper. The polyimide (PI) substrate-based sensor was formed
      by depositing a mixture of SnO2 nanopowder and poly-diallyldimethylammonium
      chloride (PDDAC) on as-patterned interdigitated electrodes. PDDAC acted both as
      the binder, promoting the adhesion between SnO2 and the flexible PI substrate,
      and the dopant. We found that the response of SnO2-PDDAC sensor is significantly
      higher than that of SnO2 alone, indicating that the doping with PDDAC effectively
      improved the sensor performance. The SnO2-PDDAC sensor has a detection limit of
      10 ppm at room temperature and shows good selectivity to ethanol, making it very
      suitable for monitoring drunken driving. The microstructures of the samples were
      examined by scanning electron microscopy (SEM), X-ray diffraction (XRD),
      transmission electron microscope (TEM) and Fourier transform infrared spectra (FT
      IR), and the sensing mechanism is also discussed in detail.

PMID- 23549364
TI  - Numerical analysis of piezoelectric active repair in the presence of frictional
      contact conditions.
AB  - The increasing development of smart materials, such as piezoelectric and shape
      memory alloys, has opened new opportunities for improving repair techniques.
      Particularly, active repairs, based on the converse piezoelectric effect, can
      increase the life of a structure by reducing the crack opening. A deep
      characterization of the electromechanical behavior of delaminated composite
      structures, actively repaired by piezoelectric patches, can be achieved by
      considering the adhesive layer between the host structure and the repair and by
      taking into account the frictional contact between the crack surfaces. In this
      paper, Boundary Element (BE) analyses performed on delaminated composite
      structures repaired by active piezoelectric patches are presented. A two
      dimensional boundary integral formulation for piezoelectric solids based on the
      multi-domain technique to model the composite host damaged structures and the
      bonded piezoelectric patches is employed. An interface spring model is also
      implemented to take into account the finite stiffness of the bonding layers and
      to model the frictional contact between the delamination surfaces, by means of an
      iterative procedure. The effect of the adhesive between the plies of
      piezoelectric bimorph devices on the electromechanical response is first pointed
      out for both sensing and actuating behavior. Then, the effect of the frictional
      contact condition on the fracture mechanics behavior of actively repaired
      delaminated composite structures is investigated.

PMID- 23549365
TI  - Pressure-sensitive paint measurements of transient shock phenomena.
AB  - Measurements of the global pressure field created by shock wave diffraction have
      been captured optically using a porous pressure-sensitive paint. The pressure
      field created by a diffracting shock wave shows large increases and decreases in
      pressure and can be reasonably accurately captured using CFD. The substrate, a
      thin-layer chromatography (TLC) plate, has been dipped in a luminophore solution.
      TLC plates are readily available and easy to prepare. Illumination comes from two
      high-intensity broadband Xenon arc light sources with short-pass filters. The
      sample is imaged at 100 kHz using a Vision Research Phantom V710 in conjunction
      with a pair of long and short pass filters, creating a band. The PSP results are
      compared with numerical simulations of the flow using the commercial CFD package
      Fluent as part of ANSYS 13 for two Mach numbers.

PMID- 23549366
TI  - Dosimeter-type NOx sensing properties of KMnO4 and its electrical conductivity
      during temperature programmed desorption.
AB  - An impedimetric NOx dosimeter based on the NOx sorption material KMnO4 is
      proposed. In addition to its application as a low level NOx dosimeter, KMnO4
      shows potential as a precious metal free lean NOx trap material (LNT) for NOx
      storage catalysts (NSC) enabling electrical in-situ diagnostics. With this
      dosimeter, low levels of NO and NO2 exposure can be detected electrically as
      instantaneous values at 380  degrees C by progressive NOx accumulation in the
      KMnO4 based sensitive layer. The linear NOx sensing characteristics are recovered
      periodically by heating to 650  degrees C or switching to rich atmospheres.
      Further insight into the NOx sorption-dependent conductivity of the KMnO4-based
      material is obtained by the novel eTPD method that combines electrical
      characterization with classical temperature programmed desorption (TPD). The NOx
      loading amount increases proportionally to the NOx exposure time at sorption
      temperature. The cumulated NOx exposure, as well as the corresponding NOx loading
      state, can be detected linearly by electrical means in two modes: (1) time
      continuously during the sorption interval including NOx concentration information
      from the signal derivative or (2) during the short-term thermal NOx release.

PMID- 23549367
TI  - SAR image simulation in the time domain for moving ocean surfaces.
AB  - This paper presents a fundamental simulation method to generate synthetic
      aperture radar (SAR) images for moving ocean surfaces. We have designed the
      simulation based on motion induced modulations and Bragg scattering, which are
      important features of ocean SAR images. The time domain simulation is able to
      obtain time series of microwave backscattering modulated by the orbital motions
      of ocean waves. Physical optics approximation is applied to calculate microwave
      backscattering. The computational grids are smaller than transmit microwave to
      demonstrate accurate interaction between electromagnetic waves and ocean surface
      waves. In this paper, as foundations for SAR image simulation of moving ocean
      surfaces, the simulation is carried out for some targets and ocean waves. The SAR
      images of stationary and moving targets are simulated to confirm SAR signal
      processing and motion induced modulation. Furthermore, the azimuth signals from
      the regular wave traveling to the azimuth direction also show the azimuthal
      shifts due to the orbital motions. In addition, incident angle dependence is
      simulated for irregular wind waves to compare with Bragg scattering theory. The
      simulation results are in good agreement with the theory. These results show that
      the simulation is applicable for generating numerical SAR images of moving ocean
      surfaces.

PMID- 23549368
TI  - Formaldehyde gas sensors: a review.
AB  - Many methods based on spectrophotometric, fluorometric, piezoresistive,
      amperometric or conductive measurements have been proposed for detecting the
      concentration of formaldehyde in air. However, conventional formaldehyde
      measurement systems are bulky and expensive and require the services of highly
      trained operators. Accordingly, the emergence of sophisticated technologies in
      recent years has prompted the development of many microscale gaseous formaldehyde
      detection systems. Besides their compact size, such devices have many other
      advantages over their macroscale counterparts, including a real-time response, a
      more straightforward operation, lower power consumption, and the potential for
      low-cost batch production. This paper commences by providing a high level
      overview of the formaldehyde gas sensing field and then describes some of the
      more significant real-time sensors presented in the literature over the past 10
      years or so.

PMID- 23549369
TI  - Highly efficient core-shell CuInS2-Mn doped CdS quantum dot sensitized solar
      cells.
AB  - A simple aqueous solution route has been used to prepare mercaptoacetic acid
      attached CuInS2 quantum dots. Based on this material, core-shell CuInS2-Mn doped
      CdS quantum dot sensitized solar cells are assembled and a power conversion
      efficiency of 5.38% is obtained under AM1.5 (100 mW cm(-2)) illumination.

PMID- 23549370
TI  - The spatial dependency of shoulder muscle demands for seated lateral hand force
      exertions.
AB  - As the modern workplace is dominated by submaximal repetitive tasks, knowledge of
      the effect of task location is important to ensure workers are unexposed to
      potentially injurious demands imposed by repetitive work in awkward or sustained
      postures. The purpose of this investigation was to develop a three-dimensional
      spatial map of the muscle activity for the right upper extremity during laterally
      directed submaximal force exertions. Electromyographic (EMG) activity was
      recorded from fourteen muscles surrounding the shoulder complex as the
      participants exerted 40N of force in two directions (leftward, rightward) at 70
      defined locations. Hand position in both push directions strongly influenced
      total and certain individual muscle demands as identified by repeated measures
      analysis of variance (P < .001). During rightward exertions individual muscle
      activation varied from 1 to 21% MVE and during leftward exertions it varied from
      1 to 27% MVE with hand location. Continuous prediction equations for muscular
      demands based on three-dimensional spatial parameters were created with explained
      variance ranging from 25 to 73%. The study provides novel information for
      evaluating existing and proactive workplace designs, and may help identify
      preferred geometric placements of lateral exertions in occupational settings to
      lower muscular demands, potentially mitigating fatigue and associated
      musculoskeletal risks. 

PMID- 23549371
TI  - Factors associated with receipt of 2009 pandemic influenza A (H1N1) monovalent
      and seasonal influenza vaccination among school-aged children: Maricopa County,
      Arizona, 2009-2010 influenza season.
AB  - CONTEXT: To target school-aged children (SAC), who were identified as a priority
      for pandemic 2009 Influenza A (pH1N1) vaccination, Maricopa County (MC) initiated
      school-based influenza vaccination in 69% of its 706 schools during the 2009-2010
      influenza season. OBJECTIVE: To determine factors associated with receipt of
      pH1N1 monovalent and 2009-2010 seasonal influenza vaccination among SAC and
      evaluate the association of school-based vaccination with vaccination status of
      SAC. DESIGN: Random-digit dialing was used to survey 600 MC households with
      willing adult participants and children grades K-12. Logistic regression was used
      to identify factors associated with pH1N1 and seasonal vaccine receipt. SETTING:
      Arizona. PARTICIPANTS: Household adults with children grades K-12. MAIN OUTCOME
      MEASURE: Characteristics of children, parents, and households were obtained.
      RESULTS: Among 909 SAC, 402 (44%) received pH1N1 and 436 (48%) received seasonal
      vaccination. Factors associated with pH1N1 vaccination included vaccine
      availability at school (adjusted odds ratio [AOR]: 1.6; 95% confidence interval
      [CI]: 1.0-2.7), high-risk medical condition in child (AOR: 2.4; 95% CI: 1.4-4.0),
      elementary versus high school attendance (AOR: 1.6; 95% CI: 1.0-2.7), and
      seasonal influenza vaccination (AOR: 10.0; 95% CI: 6.4-15.6). Factors associated
      with seasonal vaccination included Hispanic ethnicity (AOR: 2.2; 95% CI: 1.1
      4.2), health insurance coverage (AOR: 4.8; 95% CI: 1.7-13.7), elementary versus
      high school attendance (AOR: 1.5; 95% CI: 1.0-2.5), and pH1N1 vaccination (AOR:
      10.5; 95% CI: 6.7-16.6). CONCLUSIONS: Availability of pH1N1 vaccine at school was
      independently associated with pH1N1 vaccination of MC school-aged children.
      School-based influenza vaccination campaigns should be considered to increase
      vaccination among this population.

PMID- 23549372
TI  - Driving a public health culture of quality: how far down the highway have local
      health departments traveled?
AB  - CONTEXT: There has been an extensive investment in building public health
      organizational capacity to improve performance and prepare for accreditation. An
      evolving perspective has focused not only on the practice of quality improvement
      (QI) within the health department but also upon the extent the culture of QI is
      embraced within the agency. OBJECTIVE: No studies have examined the current
      national baseline of QI culture implementation, nor estimated the degree of QI
      sophistication local health departments (LHDs) have attained. We attempt to fill
      this void by aligning the findings from the QI module of the National Association
      of County & City Health Officials (NACCHO) 2010 Profile of LHDs against the
      constructs defined by the QI Maturity Tool and the NACCHO QI Roadmap (Roadmap to
      a Culture of Quality Improvement). DESIGN: Specific questions regarding QI
      activities from the 2010 Profile Study QI module were used to assign responding
      LHDs to stages within the Roadmap. We also used data from the QI Maturity Tool
      administered to all LHDs in the 16 participating Multi-State Learning
      Collaborative states in 2010 and 2011. On the basis of this matched set, we
      applied the summative domain scores algorithm, classified agencies into 1 of 5
      groups, compared our findings with those of the NACCHO survey, and aligned our
      categories to those of the Roadmap. RESULTS: Nearly 80% of LHDs classified using
      the NACCHO Profile data were assigned to group 3 or 4 versus 48% using the QI
      Maturity Tool. Results from the cross-tabulations of the matched data set between
      the QI Maturity Tool classifications and the NACCHO Profile classifications
      revealed exact alignment 30% of the time. Forty-nine of 163 agencies were
      classified in the same grouping in both schemata. In addition, 84% of the
      agencies were classified within 1 neighboring category. CONCLUSIONS: The results
      revealed that half, if not most, LHDs fall within the middle categories of QI
      maturity and sophistication, regardless of which classification system was
      deployed.

PMID- 23549373
TI  - Three-dimensional graphene foam as a biocompatible and conductive scaffold for
      neural stem cells.
AB  - Neural stem cell (NSC) based therapy provides a promising approach for neural
      regeneration. For the success of NSC clinical application, a scaffold is required
      to provide three-dimensional (3D) cell growth microenvironments and appropriate
      synergistic cell guidance cues. Here, we report the first utilization of graphene
      foam, a 3D porous structure, as a novel scaffold for NSCs in vitro. It was found
      that three-dimensional graphene foams (3D-GFs) can not only support NSC growth,
      but also keep cell at an active proliferation state with upregulation of Ki67
      expression than that of two-dimensional graphene films. Meanwhile, phenotypic
      analysis indicated that 3D-GFs can enhance the NSC differentiation towards
      astrocytes and especially neurons. Furthermore, a good electrical coupling of 3D
      GFs with differentiated NSCs for efficient electrical stimulation was observed.
      Our findings implicate 3D-GFs could offer a powerful platform for NSC research,
      neural tissue engineering and neural prostheses.

PMID- 23549374
TI  - Influence of type of nocturia and lower urinary tract symptoms on therapeutic
      outcome in women treated with desmopressin.
AB  - PURPOSE: To investigate the type of nocturia and concomitant voiding dysfunction
      (VD) and the effect of desmopressin treatment on nocturia in women. MATERIALS AND
      METHODS: We reviewed 84 women who experienced more than 2 nocturia episodes as
      recorded on a pretreatment frequency volume chart and who were treated with
      desmopressin. All patients underwent history taking, physical examination,
      urinalysis, International Prostate Symptom Score assessment, completion of a
      urinary sensation scale, and completion of a 3 day frequency volume chart.
      Nocturia was divided into nocturnal polyuria (NP), reduced nocturnal bladder
      capacity (RNBC), and mixed type. After treatment with desmopressin, a reduction
      in nocturia of over 50% compared with baseline was regarded as effective.
      RESULTS: Among 84 women, the most common concomitant VD was overactive bladder
      (OAB, 60.7%). NP was observed in 70.2% (59/84) of the women, RNBC in 7.1% (6/84),
      and mixed type in 22.6% (19/84). After medication with desmopressin, 73 women
      (86.9%) showed a significantly reduced number of nocturia episodes (1.4+/-1.5)
      compared with baseline (3.7+/-1.3, p<0.05). Eleven women (13.1%) did not show
      improvement. Of the 73 women who showed improvement, 41 women showed a reduction
      of more than 50% over baseline, and these women had a lower baseline urgency
      grade. CONCLUSIONS: In the majority of women, nocturia coexisted with other VD
      such as OAB. Treatment with desmopressin effectively reduced the nocturia.
      However, other lower urinary tract symptoms (LUTS) such as urgency may reduce the
      effect of desmopressin. Therefore, consideration of concomitant LUTS seems to be
      necessary to increase the treatment effect of desmopressin on nocturia in women.

PMID- 23549375
TI  - New insights into sickle cell disease: a disease of hypoxia.
AB  - PURPOSE OF REVIEW: Sickle cell disease (SCD) is a devastating genetic disorder
      caused by a single amino acid substitution in beta-globin. Although the condition
      was first described more than a 100 years ago, treatment options remain scarce
      and unsatisfactory. This review summarizes recent findings that may provide novel
      insight into therapeutic approaches to SCD treatment. RECENT FINDINGS: Because of
      insufficient numbers of erythrocytes for oxygen delivery, SCD patients constantly
      face hypoxia. Adenosine is well known as a key signaling nucleoside that
      orchestrates a multifaceted physiological response to hypoxia. Recent studies
      have revealed that adenosine concentrations are significantly elevated in SCD and
      contribute to disease pathology by activating adenosine receptors on red blood
      cells. Apart from adenosine, hypoxia also causes hemoglobin release via
      hemolysis. Studies on free hemoglobin in circulation have uncovered another two
      important molecules: nitric oxide and heme oxygenase-1. SUMMARY: The core of SCD
      pathology is erythrocyte sickling under hypoxic conditions, leading to vaso
      occlusion and hemolysis. Deeper and more comprehensive understanding of SCD as a
      disease of hypoxia will provide us new therapeutic targets for SCD treatment.

PMID- 23549376
TI  - The role of PET/CT in cervical cancer.
AB  - In locally advanced cervical cancer, (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography - computed tomography (PET/CT) has become important in the
      initial evaluation of disease extent. It is superior to other imaging modalities
      for lymph node status and distant metastasis. PET-defined cervical tumor volume
      predicts progression-free and overall survival. Higher FDG uptake in both primary
      and regional lymph nodes is strongly predictive of worse outcome. FDG-PET is
      useful for assessing treatment response 3 months after completing concurrent
      chemo-radiotherapy (CRT) and predicting long-term survival, and in suspected
      disease recurrence. In the era of image-guided adaptive radiotherapy, accurately
      defining disease areas is critical to avoid irradiating normal tissue. Based on
      additional information provided by FDG-PET, radiation treatment volumes can be
      modified and higher doses to FDG-positive lymph nodes safely delivered. FDG
      PET/CT has been used for image-guided brachytherapy of FDG-avid tumor volume,
      while respecting low doses to bladder and rectum. Despite survival improvements
      due to CRT in cervical cancer, disease recurrences continue to be a major
      problem. Biological rationale exists for combining novel non-cytotoxic agents
      with CRT, and drugs targeting specific molecular pathways are under clinical
      development. The integration of these targeted therapies in clinical trials, and
      the need for accurate predictors of radio-curability is essential. New molecular
      imaging tracers may help identifying more aggressive tumors. (64)Cu-labeled
      diacetyl-di(N(4)-methylthiosemicarbazone) is taken up by hypoxic tissues, which
      may be valuable for prognostication and radiation treatment planning. PET/CT
      imaging with novel radiopharmaceuticals could further impact cervical cancer
      treatment as surrogate markers of drug activity at the tumor microenvironment
      level. The present article reviews the current and emerging role of PET/CT in the
      management of cervical cancer.

PMID- 23549378
TI  - Staying hydrated: the molecular journey of gaseous sulfur dioxide to a water
      surface.
AB  - A water surface is a dynamic and constantly evolving terrain producing a vast
      array of unique molecular properties and interactions with chemical species in
      the environment. The complex dynamics of water surfaces permit life on earth to
      continue, but also complicate the development of a complete microscopic picture
      of the specific behaviors that take place within interfacial aqueous
      environments. This computational study examines a piece of the water puzzle by
      elucidating the bonding, dynamic interactions, and hydrate structures of sulfur
      dioxide gas adsorbing to a water cluster. Results described herein address the
      specific ways in which sulfur dioxide gas molecules bind to a water cluster, and
      paint a more complete picture of the adsorption pathway than was previously
      developed from experimental and computational studies. Ab initio molecular
      dynamics have been employed to study sulfur dioxide and water interactions at two
      environmentally relevant temperatures on a water cluster. The results of this
      study on a common environmental and industrially important gas provide molecular
      insight to aid our understanding of interactions on aqueous surfaces, and gaseous
      adsorption processes.

PMID- 23549377
TI  - A pig model of the human gastrointestinal tract.
AB  - Easy access to next generation sequencing has enabled the rapid analysis of
      complex microbial populations. To take full advantage of these technologies,
      animal models enabling the manipulation of human microbiomes and the study of the
      impact of such perturbations on the host are needed. To this aim we are
      developing experimentally tractable and clinically relevant pig models of the
      human adult and infant gastro-intestinal tract. The intestine of germ-free
      piglets was populated with human adult or infant fecal microbial populations, and
      the piglets were maintained on solid or milk diet, respectively. Amplicons of 16S
      rRNA V6 region were deep-sequenced to monitor to what extent the transplanted
      human microbiomes changed in the pig. Within 24 h of transfer of human fecal
      microbiome to pigs, bacterial microbiomes rich in Proteobacteria emerged. These
      populations evolved toward a more diverse composition rich in Bacteroidetes and
      Firmicutes. In the experiment where infant microbiome was used, the phylogenetic
      composition of the transplanted bacterial population converged toward that of the
      human inoculum. A majority of sequences belonged to a relatively small number of
      operational taxonomic units, whereas at the other end of the abundance spectrum,
      a large number of rare and transient OTUs were detected. Analysis of fecal and
      colonic microbiomes originating from the same animal indicate that feces closely
      replicate the colonic microbiome. We conclude that the pig intestine can be
      colonized with human fecal microbiomes to generate a realistic model of the human
      GI tract.

PMID- 23549379
TI  - Genetic elimination of eNOS reduces secondary complications of experimental
      subarachnoid hemorrhage.
AB  - Delayed complications of subarachnoid hemorrhage (SAH) such as angiographic
      vasospasm, cortical spreading ischemia, microcirculatory dysfunction, and
      microthrombosis are reported in both patients and animal models of SAH. We
      demonstrated previously that SAH is associated with increased oxidative stress in
      the brain parenchyma, and that this correlates with dysfunction of endothelial
      nitric oxide synthase (eNOS) (homodimeric uncoupling). Uncoupling of eNOS
      exacerbated oxidative stress and enhanced nitric oxide (NO) depletion, and was
      associated with multiple secondary complications such as microthrombosis,
      neuronal apoptosis, and release of reactive oxygen species. Thus, we hypothesized
      that genetic abbrogation of eNOS would confer a beneficial effect on the brain
      after SAH. Using a prechiasmatic injection model of SAH, we show here that eNOS
      knockout (KO) significantly alleviates vasospasm of the middle cerebral artery
      and reduces superoxide production. Endothelial nitric oxide synthase KO also
      affected other nitric oxide synthase isoforms. It significantly increases neuron
      nitric oxide synthase expression but has no effect on inducible nitric oxide
      synthase. Endothelial nitric oxide synthase KO decreases Zn(2+) release after
      SAH, reduces microthrombi formation, and prevent neuronal degeneration. This work
      is consistent with our findings where, after SAH, increased oxidative stress can
      uncouple eNOS via Zn(2+) thiolate oxidation, or theoretically by depletion or
      oxidation of tetrahydrobiopterin, resulting in a paradoxical release of
      superoxide anion radical, further exacerbating oxidative stress and microvascular
      damage. 

PMID- 23549381
TI  - The sonic hedgehog pathway mediates brain plasticity and subsequent functional
      recovery after bone marrow stromal cell treatment of stroke in mice.
AB  - Bone marrow stromal cells (MSCs) improve neurologic recovery after middle
      cerebral artery occlusion (MCAo). To examine whether in vivo blockage of the
      endogenous sonic hedgehog (Shh) pathway affects grafted MSC-induced neurologic
      benefits, MCAo mice were administered: vehicle (control); cyclopamine (CP)- a
      specific Shh pathway inhibitor; MSC; and MSC and cyclopamine (MSC-CP). Neurologic
      function was evaluated after MCAo. Electron microscopy and immunofluorescence
      staining were employed to measure synapse density, protein expression of tissue
      plasminogen activator (tPA), and Shh in parenchymal cells in the ischemic
      boundary zone (IBZ), respectively. Marrow stromal cell treatment significantly
      enhanced functional recovery after ischemia, concurrent with increases of
      synaptophysin, synapse density, and myelinated axons along the IBZ, and
      significantly increased tPA and Shh expression in astrocytes and neurons compared
      with control. After treatment with MSC-CP or CP, the above effects were reversed.
      Co-culture of MSCs with cortical neurons confirmed the effect of Shh on MSC
      mediated neurite outgrowth. Our data support the hypothesis that the Shh pathway
      mediates brain plasticity via tPA and thereby functional recovery after treatment
      of stroke with MSCs. 

PMID- 23549382
TI  - Leukocyte DNA damage and wound infection after nitrous oxide administration: a
      randomized controlled trial.
AB  - BACKGROUND: Nitrous oxide inactivates methionine synthase and may lead to DNA
      damage and wound infection. By using single-cell gel electrophoresis (comet
      assay), the authors determined the effect of nitrous oxide on DNA damage in
      circulating leukocytes. METHODS: In this double-blind, randomized controlled
      trial, 91 patients undergoing major colorectal surgery were randomized to receive
      70% nitrous oxide (n = 31) or nitrous oxide-free anesthesia using 30 (n = 30) or
      80% (n = 30) oxygen. Venous blood was collected before and 24 h after surgery.
      The primary outcome was extent of DNA damage, quantified as the percentage of DNA
      staining intensity in the comet tail using digital fluorescence microscopy.
      Incidence of postoperative wound infection was also recorded. RESULTS: Nitrous
      oxide exposure was associated with a two-fold increase in the percentage of DNA
      intensity in tail (P = 0.0003), but not in the 30 (P = 0.181) or 80% oxygen
      groups (P = 0.419). There was a positive correlation between the duration of
      nitrous oxide exposure and extent of DNA damage, r = 0.33, P = 0.029. However, no
      correlation was observed in nitrous oxide-free patients. The proportions of
      postoperative wound infection, using the Centers for Disease Control and
      Prevention criteria, were 19.4% (6 of 31) in the 70% nitrous oxide group and 6.7%
      (2 of 30) in both the 30 and 80% oxygen groups, P = 0.21. An increase in DNA
      damage was associated with a higher risk of wound infection, adjusted odds ratio
      (95% CIs): 1.19 (1.07-1.34), P = 0.003. CONCLUSIONS: Nitrous oxide increased DNA
      damage compared with nitrous oxide-free anesthesia and was associated with
      postoperative wound infection.

PMID- 23549380
TI  - Ionic transporter activity in astrocytes, microglia, and oligodendrocytes during
      brain ischemia.
AB  - Glial cells constitute a large percentage of cells in the nervous system. During
      recent years, a large number of studies have critically attributed to glia a new
      role which no longer reflects the long-held view that glia constitute solely a
      silent and passive supportive scaffolding for brain cells. Indeed, it has been
      hypothesized that glia, partnering neurons, have a much more actively
      participating role in brain function. Alteration of intraglial ionic homeostasis
      in response to ischemic injury has a crucial role in inducing and maintaining
      glial responses in the ischemic brain. Therefore, glial transporters as potential
      candidates in stroke intervention are becoming promising targets to enhance an
      effective and additional therapy for brain ischemia. In this review, we will
      describe in detail the role played by ionic transporters in influencing
      astrocyte, microglia, and oligodendrocyte activity and the implications that
      these transporters have in the progression of ischemic lesion. 

PMID- 23549383
TI  - The effectiveness gap in COPD: a mixed methods international comparative study.
AB  - BACKGROUND: There has been a large increase in treatment and in research on
      chronic obstructive pulmonary disease (COPD) from the common starting point of
      the original Global Initiative for Chronic Obstructive Lung Disease (GOLD) study.
      There is currently little evidence on the degree of similarity and difference
      between national programmes or on the linkage between research and policy. AIMS:
      To review the evidence on programme development and the effectiveness gap from
      the UK, France, Germany, and Finland. METHODS: Visits and literature reviews were
      undertaken for regional centres in Lancashire, Nord-Pas de Calais, and Finland,
      and Eurostat data on mortality and hospital discharges were analysed, and
      telephone interviews in Nord-Rhein Westphalia. RESULTS: There have been very
      significant differences in programme development from the original GOLD starting
      point. The UK has national strategies but they are without consistent local
      delivery. The French Affection de Longue Duree (ALD) programme limits special
      help to at most 10% of patients and there is little use of spirometry in primary
      care. Germany has a more general Disease Management Programme with COPD as a late
      starter. Finland has had a successful 10-year programme. The results for the
      effectiveness gap on hospital discharges show a major difference between Finland
      (40.7% fall in discharges) and others (increases of 6.0-43.7%). CONCLUSIONS: The
      results show the need for a simpler programme in primary care to close the
      effectiveness gap. Such a programme is outlined based on preventing the downward
      spiral for high-risk patients.

PMID- 23549384
TI  - Comparing Bayesian and frequentist approaches for multiple outcome mixed
      treatment comparisons.
AB  - OBJECTIVES: Bayesian statistical methods are increasingly popular as a tool for
      meta-analysis of clinical trial data involving both direct and indirect treatment
      comparisons. However, appropriate selection of prior distributions for unknown
      model parameters and checking of consistency assumptions required for modeling
      remain particularly challenging. We compared Bayesian and traditional frequentist
      statistical methods for mixed treatment comparisons with multiple binary
      outcomes. DATA: We searched major electronic bibliographic databases, Food and
      Drug Administration reviews, trial registries, and research grant databases up to
      December 2011 to find randomized studies published in English that examined drugs
      for female urgency urinary incontinence (UI) on continence, improvement in UI,
      and treatment discontinuation due to harm. METHODS: We describe and fit fixed and
      random effects models in both Bayesian and frequentist statistical frameworks. In
      a hierarchical model of 8 treatments, we separately analyze 1 safety and 2
      efficacy outcomes. We produce Bayesian and frequentist treatment ranks and odds
      ratios across all drug v placebo comparisons, as well as Bayesian probabilities
      that each drug is best overall through a weighted scoring rule that trades off
      efficacy and safety. RESULTS: In our study, Bayesian and frequentist random
      effects models generally suggest the same drugs as most attractive, although
      neither suggests any significant differences between drugs. However, the Bayesian
      methods more consistently identify one drug (propiverine) as best overall,
      produce interval estimates that are generally better at capturing all sources of
      uncertainty in the data, and also permit attractive "rankograms" that visually
      capture the probability that each drug assumes each possible rank. CONCLUSIONS:
      Bayesian methods are more flexible and their results more clinically
      interpretable, but they require more careful development and specialized
      software.

PMID- 23549385
TI  - Chemistry and materials based on 5,5'-bibenzo[c][1,2,5]thiadiazole.
AB  - D-A compounds constructed from a novel building block 5,5'
      bibenzo[c][1,2,5]thiadiazole (BBTz) possess a special configuration of swivel
      cruciform, which exhibits promising potential in the solution-processed small
      molecule optoelectronic devices, e.g. OSCs and OLEDs.

PMID- 23549387
TI  - Effect of BMI on knee joint torques in ergometer rowing.
AB  - Although an authoritative panel recommended the use of ergometer rowing as a non
      weight-bearing form of exercise for obese adults, the biomechanical
      characterization of ergometer rowing is strikingly absent. We examined the
      interaction between body mass index (BMI) relative to the lower extremity
      biomechanics during rowing in 10 normal weight (BMI 18-25), 10 overweight (BMI 25
      30 kg.m-2), and 10 obese (BMI > 30 kg.m-2) participants. The results showed that
      BMI affects joint kinematics and primarily knee joint kinetics. The data revealed
      that high BMI leads to unfavorable knee joint torques, implying increased loads
      of the medial compartment in the knee joint that could be avoided by allowing
      more variable foot positioning on future designs of rowing ergometers.

PMID- 23549386
TI  - Interpreting the Epstein-Barr Virus (EBV) epigenome using high-throughput data.
AB  - The Epstein-Barr virus (EBV) double-stranded DNA genome is subject to extensive
      epigenetic regulation. Large consortiums and individual labs have generated a
      vast number of genome-wide data sets on human lymphoblastoid and other cell lines
      latently infected with EBV. Analysis of these data sets reveals important new
      information on the properties of the host and viral chromosome structure
      organization and epigenetic modifications. We discuss the mapping of these data
      sets and the subsequent insights into the chromatin structure and transcription
      factor binding patterns on latent EBV genomes. Colocalization of multiple histone
      modifications and transcription factors at regulatory loci are considered in the
      context of the biology and regulation of EBV.

PMID- 23549388
TI  - Exellent result of a mirror hand anomaly treatment.

PMID- 23549390
TI  - Magnetic resonance imaging for lung cancer.
AB  - Since the publication of the Radiologic Diagnostic Oncology Group Report in 1991,
      the clinical application of pulmonary magnetic resonance imaging (MRI) in
      patients with lung cancer has been limited. In contrast, MRI for lung cancer has
      undergone continuous development, and several promising techniques have been
      introduced to overcome the previously suggested limitations. In addition,
      comparative studies involving multidetector-row computed tomography and positron
      emission tomography or positron emission tomography/computed tomography with 2
      deoxy-2-[F]fluoro-D-glucose have shown useful new clinical applications for MRI
      in lung cancer. Moreover, MRI can provide not only morphologic information based
      on various parameters such as T1 and T2 relaxation times, tissue diffusion,
      perfusion, etc. but also functional information; it also has a significant role
      in nuclear medicine studies. In this review article, we describe recent advances
      made in MRI with respect to lung cancer, focusing on (1) detection of solid
      pulmonary nodules; (2) characterization of solid pulmonary nodules; (3) TNM
      staging assessment using chest and whole-body MRI examinations; (4) prediction of
      postsurgical lung function; and (5) prediction of tumor treatment response. We
      believe that further basic studies, as well as studies on clinical applications
      of new MRI techniques, are important for improving the management of lung cancer
      patients.

PMID- 23549389
TI  - Non-critical phase-matching fourth harmonic generation of a 1053-nm laser in an
      ADP crystal.
AB  - In current inertial confinement fusion (ICF) facilities, KDP and DKDP crystals
      are the second harmonic generation (SHG) and third harmonic generation (THG)
      materials for the Nd:glass laser (1053 nm). Based on the trend for the
      development of short wavelengths for ICF driving lasers, technical solutions for
      fourth harmonic generation (FHG) will undoubtedly attract more and more
      attention. In this paper, the rapid growth of an ADP crystal and non-critical
      phase-matching (NCPM) FHG of a 1053-nm laser using an ADP crystal are reported.
      The NCPM temperature is 33.7 degrees C. The conversion efficiency from 526 to 263
      nm is 70%, and the angular acceptance range is 55.4 mrad; these results are
      superior to those for the DKDP crystals. This research has shown that ADP
      crystals will be a competitive candidate in future ICF facilities when the
      utilisation of high-energy, high-efficiency UV lasers at wavelengths shorter than
      the present 351 nm is of interest.

PMID- 23549392
TI  - Enteroviral pathogenesis of type 1 diabetes: queries and answers.
AB  - PURPOSE OF REVIEW: Type 1 diabetes (T1D) results from interplay between genetic
      predisposition, immune system, and environmental factors. Epidemiological and
      experimental data strongly suggest a role for enteroviruses in the development of
      T1D, but a lot of controversies and unanswered questions remained. This review
      focuses on issues that are fueling debate. RECENT FINDINGS: Beyond HLA genes,
      which provide genetic susceptibility for T1D, other loci have been identified to
      be associated with the disease. There is a link between T1D and single-nucleotide
      polymorphisms (SNPs) in the interferon-induced helicase 1 (IFIH1) gene that
      encodes melanoma differentiation-associated protein 5 (MDA5). This protein is a
      cytoplasmic sensor for viruses especially coxsackieviruses B, the most
      incriminated enteroviruses in T1D pathogenesis. Upon viral infection, MDA5
      stimulates the production of mediators of the innate antiviral immune response,
      which is believed to play a role in a 'bystander activation' scenario. Rare
      variants of IFIH1 through a lost or reduced expression of the protein are
      protective against T1D, whereas common IFIH1 SNPs are associated with the
      disease. However, a clear association has not been yet established between T1D
      associated IFIH1 polymorphisms and enterovirus detection. SUMMARY: Literature
      have accumulated a lot of evidence supporting that enteroviruses can contribute,
      at least in some patients, to the pathogenesis of T1D through various mechanisms.
      But it is still a challenge to date to prove a causal relationship between
      enteroviruses and T1D. Future studies may lead to a better understanding of this
      relationship and ultimately can help toward disease prevention.

PMID- 23549394
TI  - Why precursors matter.

PMID- 23549395
TI  - Precursors in cancer epidemiology: aligning definition and function.
AB  - A precursor of a disease is a definable pathologic state that progresses directly
      to disease without a known intermediate step and whose presence substantially
      increases the likelihood of disease. Precancers, or precursors of cancer, can
      help provide detail about the dynamic pathogenesis process before clinical
      disease. Thereby, ascertainment of properly defined precancers can increase
      precision of estimates and power in epidemiologic and clinical studies. Besides
      providing targets for direct treatment and improving tools for risk assessment in
      screening programs, precancers can help establish temporal ordering of cause and
      effect; can identify relatively homogeneous subsets of cancer that have passed
      through a given precancer state; and provide a basis for choosing high-risk
      individuals for detailed longitudinal study. Although the most appropriate
      definition of the precancer will vary with its function in particular research or
      clinical applications, the proportion of cancers that progress from the precancer
      and risk of cancer progressing from the precancer can be important measures of
      the value of a precancer in translational efforts.

PMID- 23549396
TI  - Dysplastic nevi and melanoma.
AB  - Dysplastic nevi are described as being on a continuum between common acquired
      nevi and melanoma because they are morphologically and biologically intermediate
      between these 2 entities. Since initially being reported as histologic lesions
      observed in melanoma-prone families, there has been considerable debate about the
      definition of dysplastic nevi, the histologic and clinical criteria used to
      define them, and their biologic importance. Their role as precursor lesions for
      melanoma is not their primary role in their relationship to melanoma because of
      the rarity of transformation of any individual nevus to a melanoma. Although
      there is still no single, universally agreed upon histologic or clinical
      definition or even name for these nevi, dysplastic nevi should be considered
      important because of their association with an increased risk for melanoma.

PMID- 23549397
TI  - Precursors to lymphoproliferative malignancies.
AB  - We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic
      lymphocytic leukemia and monoclonal gammopathy of undetermined significance
      (MGUS) as a precursor to plasma cell disorders. These conditions are present in
      the general population and increase with age. These precursors aggregate with
      lymphoproliferative malignancies in families suggesting shared inheritance. MBL
      and MGUS may share some of the same risk factors as their related malignancies
      but data are limited. Although these conditions are characterized by enhanced
      risk for the associated malignancy, the majority of individuals with these
      conditions do not progress to malignancy. A key focus for current work is to
      identify markers that predict progression to malignancy.

PMID- 23549398
TI  - Squamous dysplasia--the precursor lesion for esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal
      cancers worldwide, and esophageal squamous dysplasia (ESD) is the only
      histopathology that predicts the development of ESCC. The prevalence of ESD
      parallels rates of invasive ESCC and is typically found in 25% or more of adults
      above the age of 35 years in populations in north central China, where risk for
      ESCC is among the highest in the world. Results of chemoprevention and early
      detection studies to prevent progression of ESD suggest that these approaches,
      coupled with emerging endoscopic therapies, offer promise for the prevention of
      esophageal cancer mortality in high-risk populations. Future research on ESD and
      ESCC should focus on finding additional modifiable risk factors and on
      identifying biomarkers to incorporate into early detection strategies.

PMID- 23549399
TI  - Human papillomavirus infection and the multistage carcinogenesis of cervical
      cancer.
AB  - This short review outlines our understanding of cervical cancer precursors,
      concentrating on the central etiologic role of persistent human papillomavirus
      infection. The stages of cervical carcinogenesis are better understood than for
      most other major cancers, providing a successful cancer etiology and prevention
      model.

PMID- 23549400
TI  - Sociodemographic inequalities in sexual activity and cervical cancer screening:
      implications for the success of human papillomavirus vaccination.
AB  - BACKGROUND: Papanicolaou smear screening has significantly reduced cervical
      cancer morbidity and mortality. However, inequalities still persist across
      different socioeconomic status (SES) groups. These inequalities have been
      associated with differential participation in screening. However, even with equal
      participation to screening, some women may still have greater risk of cervical
      cancer because of sexual behavior. We aim to identify the sociodemographic
      characteristics of women who reported greater sexual activity and/or screening
      underuse. METHODS: We used data from (i) the Canadian Community Health Survey
      2005, a population-based survey of 130,000 Canadians, and (ii) a multicenter
      study including 952 women screened for cervical cancer. RESULTS: Aboriginals and
      women with lower SES reported greater sexual activity and lower screening
      participation, which may produce synergetic effects toward higher cervical cancer
      risk. Women who did not complete high school and aboriginals were, respectively,
      3.6 and 2.5 times more likely to report sexual debut before 15 years old compared
      with women with university degree and Caucasians. Women who did not complete high
      school were 2.2 times more likely to have never been screened compared with women
      with university degree. East and South Asian women were, respectively, 4.3 and
      3.1 times more likely to have never been screened than Canadian-born women but
      reported lower levels of sexual activity and were adherent to screening
      guidelines when screened at least once. CONCLUSIONS: The success of human
      papillomavirus vaccination at reducing cervical cancer and inequalities will
      depend on achieving high coverage among high-risk subpopulations. IMPACT: These
      groups must be monitored closely, and if need be, targeted for additional
      interventions.

PMID- 23549401
TI  - Dietary fat, fatty acids, and risk of prostate cancer in the NIH-AARP diet and
      health study.
AB  - BACKGROUND: Observational studies report inconsistent associations of fat and
      fatty acids with prostate cancer. METHODS: We investigated associations between
      dietary fats and fatty acids and risk of prostate cancer in the NIH-American
      Association of Retired Persons (AARP) Diet and Health Study. Diet was assessed at
      baseline with self-administered food-frequency questionnaires. Cases were
      determined by linkage with state cancer registries. HR and 95% confidence
      intervals (CI) were estimated with Cox proportional hazards models. RESULTS:
      Among 288,268 men with average follow-up of nine years, 23,281 prostate cancer
      cases (18,934 nonadvanced and 2,930 advanced including 725 fatal cases) were
      identified. Total fat and mono- and polyunsaturated fat intakes were not
      associated with incidence of prostate cancer. Saturated fat intake was related to
      increased risk of advanced prostate cancer (HRQuintile 5 vs. Qunitile 1 (Q1 vs.
      Q5), 1.21; 95% CI, 1.00-1.46; Ptrend = 0.03) and fatal prostate cancer (HRQ5 vs.
      Q1, 1.47; 95% CI, 1.01-2.15; Ptrend = 0.04). alpha-Linolenic acid (ALA) intake
      was related to increased risk of advanced prostate cancer (HRQ5 vs. Q1, 1.17; 95%
      CI, 1.04-1.31; Ptrend = 0.01). Eicosapentanoic acid (EPA) intake was related to
      decreased risk of fatal prostate cancer (HRQ5 vs. Q1, 0.82; 95% CI, 0.64-1.04;
      Ptrend = 0.02). CONCLUSION: Our study suggests that the associations of fat and
      fatty acids differ by prostate cancer severity. Saturated fat, ALA, and EPA
      intakes were related to the risk of advanced or fatal prostate cancer but not to
      nonadvanced prostate cancer. IMPACT: Identifying factors associated with advanced
      prostate cancer could reduce morbidity and mortality.

PMID- 23549402
TI  - Occurrence of trivalent monomethyl arsenic and other urinary arsenic species in a
      highly exposed juvenile population in Bangladesh.
AB  - Following reports of high cytotoxicity and mutagenicity of monomethyl arsonous
      acid (MMA(III)) and early reports of urinary MMA(III) in arsenic-exposed
      individuals, MMA(III) has often been included in population studies. Use of
      urinary MMA(III) as an indicator of exposure and/or health risk is challenged by
      inconsistent results from field studies and stability studies, which indicate
      potential artifacts. We measured urinary arsenic species in children chronically
      exposed to arsenic in drinking water, using collection, storage, and analysis
      methods shown to conserve MMA(III). MMA(III) was easily oxidized in sample
      storage and processing, but recoveries of 80% or better in spiked urine samples
      were achieved. Attempts to preserve the distribution of MMA between trivalent and
      pentavalent forms using complexing agents were unsuccessful and MMA(III) spiked
      into treated urine samples actually showed lower stability than in untreated
      samples. In 643 urine samples from a highly exposed population from the Matlab
      district in Bangladesh stored for 3-6 months at <=-70  degrees C, MMA(III) was
      detected in 41 samples, with an estimated median value of 0.3 MUg/l, and levels
      of MMA(III) above 1 MUg/l in only two samples. The low urinary concentrations in
      highly exposed individuals and known difficulties in preserving sample oxidation
      state indicate that urinary MMA(III) is not suitable for use as an
      epidemiological biomarker. 

PMID- 23549403
TI  - Spatiotemporal variability of tetrachloroethylene in residential indoor air due
      to vapor intrusion: a longitudinal, community-based study.
AB  - The migration of volatile contaminants from groundwater and soil into indoor air
      is a potential health threat at thousands of contaminated sites across the
      country. This phenomenon, known as vapor intrusion, is characterized by spatial
      and temporal heterogeneity. This study examined short-term fluctuations in
      concentrations of tetrachloroethylene (PCE) in the indoor air of residential
      homes due to vapor intrusion in a community in San Antonio, Texas, that sits atop
      an extensive, shallow plume of contaminated groundwater. Using a community-based
      design, we removed potential indoor sources of PCE and then collected twelve 3
      day passive indoor air samples in each of the 20 homes. Results demonstrated a
      one-order-of-magnitude variability in concentration across both space and time
      among the study homes, although all measured concentrations were below risk-based
      screening levels. We found that within any given home, indoor concentrations
      increase with the magnitude of the barometric pressure drop (P=0.048) and
      humidity (P<0.001), while concentrations decrease as wind speed increases
      (P<0.001) and also during winter (P=0.001). In a second analysis to examine
      sources of spatial variability, we found that indoor air PCE concentrations
      between homes increase with groundwater concentration (P=0.030) and a slab-on
      grade (as compared with a crawl space) foundation (P=0.028), whereas
      concentrations decrease in homes without air conditioners (P=0.015). This study
      offers insights into the drivers of temporal and spatial variability in vapor
      intrusion that can inform decisions regarding monitoring and exposure assessment
      at affected sites. 

PMID- 23549404
TI  - Evaluating children's location using a personal GPS logging instrument:
      limitations and lessons learned.
AB  - Global positioning system (GPS) technology is increasingly used to assess
      geographically varying exposure in population studies. However, there has been
      limited evaluation of accuracy and completeness of personal GPS data. The ability
      of a GPS data logger to assess location of children during usual activity was
      evaluated. Data collected for 4 days from 17 children wearing GPS loggers,
      recorded every 15 s, were evaluated for completeness by time of day during
      weekend and weekdays, and for accuracy during nighttime at home. Percentage of
      possible GPS-recorded points and of 5-min intervals with at least one recorded
      location were examined. Mean percentage of total possible 15-s interval locations
      recorded daily was less than 30%. Across participants, the GPS loggers recorded 1
      47% of total possible location points on weekends and 1-55% on weekdays. More
      complete data were measured during travel to school (average 91%). The percentage
      of daily 5-min intervals with recorded data was as high as 53%. At least one
      location was recorded during 69% of 5-min intervals before school (0630-0800 h),
      62% during school (0800-1400 h) and 56% after school (1400-1700 h). During night
      time (0000-0600 h), on average, location was recorded for less than 25% of 5-min
      intervals and accuracy was poor. The large proportion of missing data limits the
      usefulness of GPS logging instruments for population studies. They have potential
      utility for assessing on-road travel time and route. GPS technology has
      limitations, and lessons learned from this evaluation can be generalized to the
      use of GPS in other research settings. 

PMID- 23549405
TI  - Calabadion: A new agent to reverse the effects of benzylisoquinoline and
      steroidal neuromuscular-blocking agents.
AB  - INTRODUCTION: To evaluate whether calabadion 1, an acyclic member of the
      Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and
      steroidal neuromuscular-blocking agent effects. METHODS: A total of 60 rats were
      anesthetized, tracheotomized, and instrumented with IV and arterial catheters.
      Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and
      neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30,
      60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium),
      or neostigmine/glycopyrrolate at 0.06/0.012 mg/kg were administered at maximum
      twitch depression, and renal calabadion 1 elimination was determined by using a H
      NMR assay. The authors also measured heart rate, arterial blood gas parameters,
      and arterial blood pressure. RESULTS: After the administration of rocuronium,
      resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9
      were accelerated from 12.3 +/- 1.1 and 16.2 +/- 3.3 min with placebo to 4.6 +/-
      1.8 min with neostigmine/glycopyrrolate to 15 +/- 8 and 84 +/- 33 s with
      calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium,
      recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 +/
      2.8 and 9.9 +/- 1.7 min with placebo to 2.8 +/- 0.8 and 7.6 +/- 2.1 min with
      neostigmine/glycopyrrolate to 47 +/- 13 and 87 +/- 16 s with calabadion 1 (150
      mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood
      pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the
      IV administered calabadion 1 appeared in the urine within 1 h. CONCLUSION:
      Calabadion 1 is a new drug for rapid and complete reversal of the effects of
      steroidal and benzylisoquinoline neuromuscular-blocking agents.

PMID- 23549406
TI  - Lentiviral vector-mediated knockdown of Lrb in the arcuate nucleus promotes diet
      induced obesity in rats.
AB  - Obesity is currently a worldwide pandemic. Leptin resistance is a main mechanism
      of obese human and rodents. The downregulation of the long form of the leptin
      receptor (Lrb) was involved in leptin resistance in diet-induced obese rats. In
      the studies, we investigated whether arcuate nucleus (ARC) silencing of Lrb would
      promote diet-induced obesity in rats. Lentiviral vectors expressing Lrb-shRNA
      were administered to 5-week-old male rats by ARC injection. Following viral
      delivery, the rats were provided with a high-fat diet (HFD) or a chow diet (CD).
      After 8 weeks of the diet, serum leptin, and insulin concentrations were measured
      by RIA, gene expression of Lrb in the ARC was detected by a real-time RT-PCR, and
      leptin signaling was examined by western blot. The Lrb-shRNA knocked down the
      expression of Lrb mRNA in infected regions by 54% for the HFD rats and 47% for
      the CD rats respectively. The Lrb knockdown reduced Stats3 activation and
      increased expression of Npy mRNA. The rats with reduced Lrb in the ARC showed a
      significant increase in energy intake and body weight (BW) again when fed with a
      HFD. By contrast, there were no effects of Lrb reduction on energy intake or BW
      when rats maintained on a low-fat chow. Our results provide evidence that Lrb
      knockdown selectively in the ARC promotes diet-induced obesity and associated
      metabolic complications in rats.

PMID- 23549407
TI  - Aldosterone directly affects apelin expression and secretion in adipocytes.
AB  - There is a high incidence of metabolic syndrome among patients with primary
      aldosteronism (PA), which has recently been associated with an unfavorable
      cardiometabolic profile. However, the underlying mechanisms have not been
      clarified in detail. Characterizing aldosterone (Ald) target genes in adipocytes
      will help us to elucidate the deleterious effects associated with excess Ald.
      Apelin, a novel adipokine, exerts beneficial effects on obesity-associated
      disorders and cardiovascular homeostasis. The objective of this study was to
      investigate the effects of high Ald levels on apelin expression and secretion and
      the underlying mechanisms involved in adipocytes. In vivo, a single-dose Ald
      injection acutely decreased apelin serum levels and adipose tissue apelin
      production, which demonstrates a clear inverse relationship between the levels of
      plasma Ald and plasma apelin. Experiments using 3T3-L1 adipocytes showed that Ald
      decreased apelin expression and secretion in a time- and dose-dependent manner.
      This effect was reversed by glucocorticoid receptor (GR) antagonists or GR
      (NR3C1) knockdown; furthermore, putative HREs were identified in the apelin
      promoter. Subsequently, we verified that both glucocorticoids and
      mineralocorticoids regulated apelin expression through GR activation, although no
      synergistic effect was observed. Additionally, detailed potential mechanisms
      involved a p38 MAPK signaling pathway. In conclusion, our findings strengthen the
      fact that there is a direct interaction between Ald and apelin in adipocytes,
      which has important implications for hyperaldosteronism or PA-associated
      cardiometabolic syndrome and hoists apelin on the list of potent therapeutic
      targets for PA.

PMID- 23549408
TI  - Orally efficacious novel small molecule 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl
      alpha-D-glucopyranose selectively and potently stimulates insulin receptor and
      alleviates diabetes.
AB  - Type 2 diabetes (T2D) has become an epidemic worldwide while T1D remains a great
      medical challenge. Insulin receptor (IR) signaling activators could alleviate
      hyperglycemia, reduce the burden on the pancreas, and contribute to prevention
      and treatment of both types of diabetes. Previously, we reported the synthesis
      and identification of a natural antidiabetic compound alpha-penta-galloyl-glucose
      (alpha-PGG). Subsequent studies led to the identification of an alpha-P6GG
      derivative, 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-alpha-D-glucopyranose (6Cl
      TGQ). Here, we report that 6Cl-TGQ not only induced rapid and long-lasting
      glucose uptake comparable to insulin in adipocytes but also reduced high blood
      glucose levels to near normal and significantly decreased plasma insulin levels
      and improved glucose tolerance performance in high-fat diet-induced T2D mice when
      administered orally at 5 mg/kg once every other day. Moreover, a single gavage of
      6Cl-TGQ at 10 mg/kg induced rapid and sharp decline of blood glucose in
      streptozotocin-induced T1D mice. Our studies further indicated that 6Cl-TGQ
      activated IR signaling in cell models and insulin-responsive tissues of mice. 6Cl
      TGQ-induced Akt phosphorylation was completely blocked by IR and PI3K inhibitors,
      while the induced glucose uptake was blocked by the same compounds and a Glut4
      inhibitor. Receptor binding studies indicated that 6Cl-TGQ bound to IR with a
      higher affinity than alpha-PGG. Importantly, 6Cl-TGQ, unlike insulin, selectively
      induced phosphorylation of IR without activating IGF1R or its signaling and did
      not increase cancer cell proliferation. These results indicate that 6Cl-TGQ is a
      potent orally efficacious compound with low carcinogenic potential and may
      contribute to the prevention and treatment of T1D and T2D.

PMID- 23549409
TI  - Fecal excretion of Bifidobacterium infantis 35624 and changes in fecal microbiota
      after eight weeks of oral supplementation with encapsulated probiotic.
AB  - Certain randomized, placebo-controlled trials of oral supplementation with B.
      infantis 35624 have demonstrated the amelioration of symptoms of irritable bowel
      syndrome. Potential GI colonization by B. infantis 35624 or effects of
      supplementation on resident GI microbiota may pertain to these clinical
      observations. In this study, fecal excretion of B. infantis 35624 before, during
      and after 8 weeks of daily treatment was compared in subjects with IBS who
      received either the encapsulated oral supplement (n = 39) or placebo (n = 37) and
      in healthy subjects who received the supplement (n = 41). Secondarily, changes in
      assessed fecal microbiota and IBS symptoms were determined. Supplementation
      significantly increased fecal B. infantis 35624 excretion vs. placebo in IBS
      subjects; excretion in healthy subjects receiving supplement was quantitatively
      similar. Fecal levels of the probiotic declined and approached baseline once
      dosing ceased, documenting that colonization is transient. Although
      supplementation increased numbers of B infantis 35624 within the GI tract,
      limited changes in 10 other fecal taxa were observed either in healthy subjects
      or those with IBS. No impact on IBS symptoms was observed. Detection of bacterial
      DNA in fecal samples suggests that the probiotic is able to survive transit
      through the GI tract, although strain selective culture techniques were not
      performed to confirm viability of B. infantis 35624 in the feces. Continuous
      probiotic administration was necessary to maintain steady-state transit. Given
      the complex spectrum of GI microbiota, however, monitoring perturbations in
      selected taxa may not be not a useful indicator of probiotic function.

PMID- 23549413
TI  - Complementary biochemical approaches applied to the identification of plastidial
      calmodulin-binding proteins.
AB  - Ca(2+)/Calmodulin (CaM)-dependent signaling pathways play a major role in the
      modulation of cell responses in eukaryotes. In the chloroplast, few proteins such
      as the NAD(+) kinase 2 have been previously shown to interact with CaM, but a
      general picture of the role of Ca(2+)/CaM signaling in this organelle is still
      lacking. Using CaM-affinity chromatography and mass spectrometry, we identified
      210 candidate CaM-binding proteins from different Arabidopsis and spinach
      chloroplast sub-fractions. A subset of these proteins was validated by an
      optimized in vitro CaM-binding assay. In addition, we designed two fluorescence
      anisotropy assays to quantitatively characterize the binding parameters and
      applied those assays to NAD(+) kinase 2 and selected candidate proteins. On the
      basis of our results, there might be many more plastidial CaM-binding proteins
      than previously estimated. In addition, we showed that an array of complementary
      biochemical techniques is necessary in order to characterize the mode of
      interaction of candidate proteins with CaM.

PMID- 23549414
TI  - Anomalous ground-state proton transfer of 4'-N,N-diethylamino-3-hydroxyflavone in
      ionic liquids of imidazolium-based cations with tetrafluoroborate.
AB  - We identified electronic ground state proton transfer reactions of 4'-N,N
      diethylamino-3-hydroxyflavone (DEAHF) in ionic liquids (ILs) of imidazolium-based
      cations with tetrafluoroborate. We found unique slow dynamics of the tautomeric
      reaction of DEAHF in ILs of imidazolium-based cations with tetrafluoroborate.

PMID- 23549415
TI  - Lower extremity mechanics during marching at three different cadences for 60
      minutes.
AB  - During group marches, soldiers must walk in step with one another at the same
      imposed cadence. The literature suggests that shorter trainees may be more
      susceptible to injury due to overstriding that can occur when taller recruits
      dictate marching cadence. This study assessed the effects of fixed cadence
      simulated marching at cadences above and below preferred step rate (PSR) on lower
      extremity joint mechanics in individuals who were unaccustomed to marching.
      During three separate visits, 13 volunteers walked with a 20 kg load on a force
      sensing treadmill at self-selected PSR, PSR+15% (shorter strides), and PSR-15%
      (longer strides) at 1.3 m/s for 60 min. Two-way RM ANOVAs (cadence by time) were
      performed during the stance phase. Ranges of motion and anteroposterior ground
      reaction force increased significantly as cadence decreased (P < .03). Knee
      extension moment increased slightly when step rate decreased from PSR+15%
      (shortest strides, 0.85 +/- 0.2 N m/kg) to PSR (0.87 +/- 0.3 N m/kg, 3%
      increase); however, this increase was substantially greater (20% increase) when
      cadence was decreased from PSR to PSR-15% (longest strides, 1.09 +/- 0.3 N m/kg).
      Our results indicate that overstriding during fixed-cadence marching is a factor
      that can substantially increase mechanical stress on lower extremity joints. 

PMID- 23549416
TI  - Phosphorylated CaMKII levels increase in rat central nervous system after large
      dose intravenous remifentanil.
AB  - BACKGROUND: Postoperative remifentanil-induced pain sensitization is common, but
      its molecular mechanism remains unclear. Calcium/calmodulin-dependent protein
      kinase II (CaMKII) has been shown to have a critical role in morphine-induced
      hyperalgesia. This study was designed to determine how CaMKII phosphorylation and
      protein expression levels change in the central nervous system of rats with
      remifentanil-induced hyperalgesia. MATERIAL AND METHODS: Male Sprague-Dawley(r)
      rats were exposed to large-dose (bolus of 6.0 ug/kg and 2.5 ug/kg/min for 2
      hours) intravenous remifentanil to induce post-transfusion hyperalgesia. Levels
      of phosphorylated CaMKII (P-CaMKII) and total protein of CaMKII (T-CaMKII) were
      determined at different post-transfusion times by Western blot and immunostaining
      and were compared with controls. RESULTS: P-CaMKII increased significantly
      (P<0.05) at 0, 0.5, and 2 hours. However, P-CaMKII at 5 to 24 hours and T-CaMKII
      at 0 to 24 hours post-transfusion did not change significantly in rats' spinal
      dorsal horn, hippocampus, or primary somatosensory (S1) cortex (n=6 per group).
      Similarly, immunostaining showed stronger P-CaMKII immunoreactants (P<0.05) and
      more P-CaMKII- positive cells (P<0.05) in the spinal dorsal horn, CA1 region of
      the hippocampus, and S1 cortex of rats 0.5 hours post-transfusion compared with
      the control group treated with 0.9% sodium chloride (n=3 per group). CONCLUSIONS:
      These results suggest that a temporary rise in the P-CaMKII level in the central
      nervous system may correlate with remifentanil-induced pain sensitization in the
      postoperative period.

PMID- 23549418
TI  - Migraine and childhood periodic syndromes in children and adolescents.
AB  - PURPOSE OF REVIEW: This review covers recent advances in our understanding of
      migraine and childhood periodic syndromes in children and adolescents, as well as
      the treatment of these disorders. RECENT FINDINGS: The childhood periodic
      syndromes include benign paroxysmal torticollis, benign paroxysmal vertigo,
      abdominal migraine, and cyclic vomiting syndrome. Recent research suggests infant
      colic may also fit into this category. Migraine headache is common in children
      and adolescents, and chronic migraine effects 0.8-1.8% of adolescents and 0.6% of
      children. Two triptans are now FDA-approved for the acute treatment of migraine
      in pediatric patients. For preventive therapy, a number of medications have been
      studied and a major national trial is ongoing. SUMMARY: Childhood periodic
      syndromes are thought to be early life expressions of those genes that later in
      life are expressed as migraine headache. Future research into mechanisms of
      identifying children with these disorders prior to extensive and often invasive
      testing would be of benefit to these families and children. Migraine-specific
      therapies are now approved for the acute treatment of migraine in pediatric
      patients. Preventive migraine therapy is indicated in appropriate patients,
      although which medications are most effective in children is an area of active
      research.

PMID- 23549417
TI  - Unique pharmacological actions of atypical neuroleptic quetiapine: possible role
      in cell cycle/fate control.
AB  - Quetiapine is an atypical neuroleptic with a pharmacological profile distinct
      from classic neuroleptics that function primarily via blockade of dopamine D2
      receptors. In the United States, quetiapine is currently approved for treating
      patients with schizophrenia, major depression and bipolar I disorder. Despite its
      widespread use, its cellular effects remain elusive. To address possible
      mechanisms, we chronically treated mice with quetiapine, haloperidol or vehicle
      and examined quetiapine-specific gene expression change in the frontal cortex.
      Through microarray analysis, we observed that several groups of genes were
      differentially expressed upon exposure to quetiapine compared with haloperidol or
      vehicle; among them, Cdkn1a, the gene encoding p21, exhibited the greatest fold
      change relative to haloperidol. The quetiapine-induced downregulation of
      p21/Cdkn1a was confirmed by real-time polymerase chain reaction and in situ
      hybridization. Consistent with single gene-level analyses, functional group
      analyses also indicated that gene sets associated with cell cycle/fate were
      differentially regulated in the quetiapine-treated group. In cortical cell
      cultures treated with quetiapine, p21/Cdkn1a was significantly downregulated in
      oligodendrocyte precursor cells and neurons, but not in astrocytes. We propose
      that cell cycle-associated intervention by quetiapine in the frontal cortex may
      underlie a unique efficacy of quetiapine compared with typical neuroleptics.

PMID- 23549419
TI  - Keratinocyte stem cells but not melanocyte stem cells are the primary target for
      radiation-induced hair graying.
AB  - Ionizing radiation (IR)-induced hair graying is caused by the ectopic
      differentiation of melanocyte stem cells (MSCs) in their niche located at the
      bulge region of the hair follicle. Keratinocyte stem cells (KSCs) in the bulge
      region are an important component of that niche. However, little is known about
      the relationship between MSC differentiation and the KSC niche during IR-induced
      hair graying. We found that both follicular MSCs and KSCs were affected by IR by
      using immunohistochemical detection of gammaH2AX as a genotoxicity marker. We
      also found that KSCs prepared from irradiated mice were functionally affected by
      IR as indicated by their reduced colony-forming activity in culture and the
      delayed hair cycle in vivo. However, these effects of IR on KSCs were temporal.
      The MSC population, which proliferated and differentiated to melanocytes, was
      persistently maintained after irradiation. In addition to the loss of colony
      forming activity, irradiated keratinocytes including KSCs suppressed the colony
      formation of MSCs in vitro. Furthermore, pigmented hairs were not reconstituted
      in vivo in the presence of irradiated KSCs or keratinocytes. These results
      provide a previously unreported insight that the primary target of IR during the
      induction of hair graying is follicular KSCs rather than MSCs. 

PMID- 23549420
TI  - Kindlin-1 mutant zebrafish as an in vivo model system to study adhesion
      mechanisms in the epidermis.
AB  - From a forward genetic screen for epidermal defects in zebrafish, we identified a
      loss-of-function mutation in Kindlin-1, an essential regulator of integrin
      function. The mutation generates a premature stop codon, deleting the integrin
      binding site. The mutant zebrafish develops cell-matrix and cell-cell adhesion
      defects in the basal epidermis leading to progressive fin rupturing, and was
      therefore designated rupturing-of-fins (rof). Similar defects were observed in
      the epidermis of Kindler syndrome patients, carrying a loss-of-function mutation
      in kindlin-1. Mutational analysis and rescue experiments in zebrafish revealed
      that residues K610, W612, and I647 in the F3 domain are essential for Kindlin-1
      function in vivo, and that Kindlin-2 can functionally compensate for the loss of
      Kindlin-1. The fin phenotype of rof/kindlin-1 mutants resembles that of badfin
      mutants, carrying a mutation in integrin alpha3. We show here that this mutation
      impairs the biosynthesis of integrin alpha3beta1 and causes cell-matrix and cell
      cell defects in vivo. Whereas both Integrin-linked kinase (Ilk) and Kindlin-1
      cooperate with Integrin alpha3beta1 to resist trauma-induced epidermal defects,
      Kindlin-1 and Ilk, surprisingly, do not act synergistically but in parallel.
      Thus, the rof/kindlin-1 mutant zebrafish provides a unique model system to study
      epidermal adhesion mechanisms in vivo. 

PMID- 23549421
TI  - Impaired epidermal ceramide synthesis causes autosomal recessive congenital
      ichthyosis and reveals the importance of ceramide acyl chain length.
AB  - The barrier function of the human epidermis is supposed to be governed by lipid
      composition and organization in the stratum corneum. Disorders of keratinization,
      namely ichthyoses, are typically associated with disturbed barrier activity.
      Using autozygosity mapping and exome sequencing, we have identified a homozygous
      missense mutation in CERS3 in patients with congenital ichthyosis characterized
      by collodion membranes at birth, generalized scaling of the skin, and mild
      erythroderma. We demonstrate that the mutation inactivates ceramide synthase 3
      (CerS3), which is synthesized in skin and testis, in an assay of N-acylation with
      C26-CoA, both in patient keratinocytes and using recombinant mutant proteins.
      Moreover, we show a specific loss of ceramides with very long acyl chains from
      C26 up to C34 in terminally differentiating patient keratinocytes, which is in
      line with findings from a recent CerS3-deficient mouse model. Analysis of
      reconstructed patient skin reveals disturbance of epidermal differentiation with
      an earlier maturation and an impairment of epidermal barrier function. Our
      findings demonstrate that synthesis of very long chain ceramides by CerS3 is a
      crucial early step for the skin barrier formation and link disorders presenting
      with congenital ichthyosis to defects in sphingolipid metabolism and the
      epidermal lipid architecture. 

PMID- 23549422
TI  - Syntaxin-3 is required for melanosomal localization of Tyrp1 in melanocytes.
AB  - Melanogenic enzymes are transported by vesicular/membrane trafficking to immature
      melanosomes in melanocytes where they catalyze the synthesis of melanin pigments.
      Although several factors involved in melanogenic enzyme trafficking have been
      identified in the past decade, involvement of the SNARE (soluble N-ethylmaleimide
      sensitive factor attachment protein receptor) proteins, which generally mediate
      membrane fusion, on melanosomes in the process of melanogenic enzyme trafficking
      has never been investigated. In this study we identified syntaxin-3, which was
      originally described as a target SNARE protein at the plasma membrane, as a
      melanosome-resident protein and investigated whether syntaxin-3 is involved in
      the trafficking of the melanogenic enzyme Tyrp1 (tyrosinase-related protein 1) in
      mouse melanocytes. The results showed that knockdown of endogenous syntaxin-3
      protein in melanocytes caused a dramatic reduction in Tyrp1 signals, especially
      from peripheral melanosomes, presumably as a result of lysosomal degradation of
      Tyrp1. They also showed that syntaxin-3 interacts with another target SNARE
      SNAP23 (synaptosome-associated protein of 23 kDa) and with vesicle SNARE VAMP7
      (vesicle-associated membrane protein 7), which has been shown to be localized at
      Tyrp1-containing vesicles/organelles. These findings suggested that the SNARE
      machinery composed of VAMP7 on Tyrp1-containing vesicles and syntaxin-3 and
      SNAP23 on melanosomes regulates Tyrp1 trafficking to the melanosome in
      melanocytes. 

PMID- 23549423
TI  - Ultrahigh-efficiency photocatalysts based on mesoporous Pt-WO3 nanohybrids.
AB  - A reliable nanocasting method has been developed to synthesize mesoporous hybrids
      of platinum (Pt) nanoparticles decorating tungsten trioxide (WO3). The process
      began with modification of the SBA-15 template with carbon polymers and Pt
      nanoparticles accompanied by adsorption of W(6+), which was then converted into m
      Pt-WO3 composites by heat treatment and subsequent template removal. The
      synthetic strategy can be easily extended to prepare other mesoporous nanohybrids
      with metal oxide loaded precious metal composites. Comprehensive
      characterizations suggest that the as-developed m-Pt-WO3 nanohybrid exhibits
      unique properties with mesoporous structure, excellent crystalline structure, and
      high surface area. When the photocatalytic properties of m-Pt-WO3 nanohybrids
      were systematically investigated, it was revealed that the m-Pt-WO3 nanohybrids
      showed great promise for degrading the organic dye under visible light
      irradiation, which shows an excellent photocatalytic activity that far exceeded
      those of pure phase mesoporous WO3 and commercial TiO2 (P25), and was 10-fold
      more active than that of the bulk Pt-WO3 catalyst. The as-developed synthetic
      route opens up a new avenue for designing mesoporous hybrid materials for various
      applications benefiting from the unique porous structure, high surface area, and
      synergistic effects among constituents.

PMID- 23549424
TI  - Endovascular repair versus open repair of ruptured abdominal aortic aneurysms: a
      multicenter randomized controlled trial.
AB  - OBJECTIVE: Randomized comparison of endovascular repair (EVAR) with open repair
      (OR) in patients with a ruptured abdominal aortic aneurysm (RAAA). BACKGROUND:
      Despite advances in operative technique and perioperative management RAAA remains
      fraught with a high rate of death and complications. Outcome may improve with a
      minimally invasive surgical technique: EVAR. METHODS: All patients with a RAAA in
      the larger Amsterdam area were identified. Logistics for RAAA patients was
      changed with centralization of care in 3 trial centers. Patients both fit for
      EVAR and for OR were randomized to either of the treatments. Nonrandomized
      patients were followed in a prospective cohort. Primary endpoint of the study was
      the composite of death and severe complications at 30 days. RESULTS: Between
      April 2004 and February 2011, we identified 520 patients with a RAAA of which 116
      could be randomized. The primary endpoint rate for EVAR was 42% and for OR was
      47% [absolute risk reduction (ARR) = 5.4%; 95% confidence interval (CI): -13% to
      +23%]. The 30-day mortality was 21% in patients assigned to EVAR compared with
      25% for OR (ARR = 4.4% 95% CI: -11% to +20%). The mortality of all surgically
      treated patients in the nonrandomized cohort was 30% (95% CI: 26%-35%) and 26%
      (95% CI: 20% to 32%) in patients with unfavorable anatomy for EVAR, treated by OR
      at trial centers. CONCLUSIONS: This trial did not show a significant difference
      in combined death and severe complications between EVAR and OR. Mortality for OR
      both in randomized patients and in cohort patients was lower than anticipated,
      which may be explained by optimization of logistics, preoperative CT imaging, and
      centralization of care in centers of expertise.

PMID- 23549426
TI  - Advantage of completely laparoscopic gastrectomy with linear stapled
      reconstruction: a long-term follow-up study.
AB  - BACKGROUND: Completely laparoscopic gastrectomy with intracorporeal anastomosis
      was introduced to achieve safer anastomosis and smaller scars. Although several
      reports have shown the feasibility of linear-stapled anastomosis, there are no
      studies of a large number of patients assessing the long-term complications and
      functional outcomes. METHODS: This retrospective study included 345 patients who
      had intended to undergo completely laparoscopic distal or total gastrectomy with
      linear-stapled anastomosis between September 2005 and January 2012. This study
      evaluated both the short- and long-term complications, as well as the endoscopic
      findings, changes in body weight and serum albumin. RESULTS: Completely
      laparoscopic gastrectomy was successfully achieved in 342 patients (99.1%). Short
      term complications occurred in 59 patients (17.3%). Reconstruction-related
      complications were observed in 19 patients (5.6%). Three patients with
      anastomotic leakage required reoperation. No patient experienced anastomotic
      stenosis over a mean follow-up period of 29.6 months. Two patients underwent an
      emergency operation for an internal hernia after total gastrectomy. Adhesive
      intestinal obstruction was observed in 5 patients (1.5%), but all were resolved
      without surgical intervention. Body weight loss at 2 years after distal and total
      gastrectomy was 7.2% and 13.9%, which were similar to previous reports of open
      surgery. CONCLUSIONS: Completely laparoscopic gastrectomy with linear-stapled
      anastomosis is a feasible choice for gastric cancer patients with some potential
      long-term advantages such as less anastomotic stenosis and fewer adhesive
      intestinal obstructions.

PMID- 23549427
TI  - The detection of intraoperative bacterial translocation in the mesenteric lymph
      nodes is useful in predicting patients at high risk for postoperative infectious
      complications after esophagectomy.
AB  - OBJECTIVE: To investigate the incidence of BT in the mesenteric lymph node and
      bacteremia after an esophagectomy using a bacterium-specific ribosomal RNA
      targeted reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR).
      BACKGROUND: There is little evidence regarding the occurrence of bacterial
      translocation (BT) and its correlation to postoperative infectious complications
      after an esophagectomy. METHODS: Eighteen patients with esophageal cancer were
      studied. Mesenteric lymph nodes were harvested from the jejunal mesentery before
      surgical mobilization (MLN-1) and after the restoration of bowel continuity (MLN
      2). Blood and sputum were also sampled before surgery (Blood-1 and Sputum-1) and
      on postoperative day 1 (Blood-2 and Sputum-2). RESULTS: The detection rates of
      bacteria in the MLN-2 (56%) and Blood-2 (56%) were significantly higher than
      those in the MLN-1 (17%) and Blood-1 (22%), indicating that surgical stress
      induces BT. The detection rate was not different between Sputum-1 (80%) and
      Sputum-2 (78%). There was an 80% sequence homology between the RT-qPCR products
      in the MLN-2 and Blood-2, whereas the homology was only 20% between Blood-2 and
      Sputum-2. In the patients with positive bacteria in the MLN-2 sample, there was a
      greater incidence of postoperative infectious complications than in patients
      without bacteria in the MLN-2 sample (P = 0.04). The postoperative hospital stay
      was also longer (P = 0.037) for patients with positive bacteria in the MLN-2
      sample. CONCLUSIONS: BT frequently occurs during esophagectomies, and
      postoperative bacteremia is likely to be gut-derived. Patients with positive
      bacteria in the MLN-2 sample should be carefully managed because these patients
      are more susceptible to postoperative infectious complications.

PMID- 23549425
TI  - Poly-ADP-ribose-polymerase inhibition ameliorates hind limb ischemia reperfusion
      injury in a murine model of type 2 diabetes.
AB  - INTRODUCTION: Diabetes is known to increase poly-ADP-ribose-polymerase (PARP)
      activity and posttranslational poly-ADP-ribosylation of several regulatory
      proteins involved in inflammation and energy metabolism. These experiments test
      the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion
      (IR) in a mouse model of type-II diabetes and ameliorate the ribosylation and the
      activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). METHODS: db/db mice underwent 1.5 hours of hind
      limb ischemia followed by 1, 7, or 24 hours of reperfusion. The treatment group
      received the PARP inhibitor PJ34 (PJ34) over a 24-hour period; the untreated
      group received Lactated Ringer (LR) at the same time points. IR muscles were
      analyzed for indices of PARP activity, fiber injury, metabolic activity,
      inflammation, GAPDH activity/intracellular localization, and poly-ADP
      ribosylation of GAPDH. RESULTS: PARP activity was significantly lower in the PJ34
      treated groups than in the Lactated Ringer group at 7 and 24 hours of
      reperfusion. There was significantly less muscle fiber injury in the PJ34-treated
      group than in the Lactated Ringer-treated mice at 24 hours of reperfusion. PJ34
      lowered levels of select proinflammatory molecules at 7 hours and 24 hours of IR.
      There were significant increases in metabolic activity only at 24 hours of IR in
      the PJ34 group, which temporally correlated with increase in GAPDH activity,
      decreased GAPDH poly-ADP-ribosylation, and nuclear translocation of GAPDH.
      CONCLUSIONS: PJ34 reduced PARP activity, GAPDH ribosylation, and GAPDH
      translocation; ameliorated muscle fiber injury; and increased metabolic activity
      after hind limb IR injury in a murine model of type-II diabetes. PARP inhibition
      might be a therapeutic strategy after IR in diabetic humans.

PMID- 23549428
TI  - Real time cancer prediction based on objective tissue compliance measurement in
      endoscopic surgery.
AB  - OBJECTIVE: To investigate the feasibility of real time cancer tissue diagnosis
      intraoperatively based on in vivo tissue compliance measurements obtained by a
      recently developed laparoscopic smart device. BACKGROUND: Cancer tissue is
      stiffer than its normal counterpart. Modern forms of remote surgery such as
      laparoscopic and robotic surgical techniques diminish direct assessment of this
      important tissue property. In vivo human tissue compliance of the normal and
      cancer gastrointestinal tissue is unknown. A Clinical Real Time Tissue Compliance
      Mapping System (CRTCMS) with a predictive power comparable to the human hand and
      useable in routine surgical practice has been recently developed. METHODS: The
      CRTCMS is employed in the operating theater to collect data from 50 patients
      undergoing intra-abdominal surgical interventions [40 men, 10 women, aged between
      32 and 89 (mean = 66.4, range = 57)]. This includes 10 esophageal and 27 gastric
      cancer patients. A total of 1212 compliance measurements of normal and cancerous
      in vivo gastrointestinal tissues were taken. The data were used to calibrate the
      CRTCMS to predict cancerous tissue in a further 12 patients (3 cancer esophagus
      and 9 cancer stomach) involving 175 measurements. RESULTS: The system
      demonstrated a high prediction power to diagnose cancer tissue in real time
      during routine surgical procedures (sensitivity = 98.7%, specificity = 99%). An
      in vivo human tissue compliance data bank of the gastrointestinal tract was
      produced. CONCLUSIONS: Real time cancer diagnosis based on in vivo tissue
      compliance measurements is feasible. The reported data open new avenues in cancer
      diagnostics, surgical robotics, and development of more realistic surgical
      simulators.

PMID- 23549429
TI  - Discovery of Rho-kinase inhibitors by docking-based virtual screening.
AB  - Rho kinases (ROCK1 and ROCK2) belong to serine/threonine (Ser/Thr) protein kinase
      family, and play the central roles in the organization of the actin cytoskeleton.
      Therefore, Rho kinases have become attractive targets for the treatments of many
      diseases, such as cancer, renal disease, hypertension, ischemia, and stroke. In
      order to develop small-molecule inhibitors of ROCK1, molecular docking was
      utilized to virtually screen two chemical databases and identify molecules that
      interact with ROCK1. A small set of virtual hits was purchased and submitted to a
      series of experimental assays. The in vitro enzyme-based and cell-based assays
      reveal that 12 compounds have good inhibitory activity against ROCK1 in the micro
      molar regime (IC50 values between about 7 and 28 MUM) and antitumor activity
      against lung cancer, breast cancer or/and myeloma cell lines. The structural
      analysis shows that two active compounds present novel scaffolds and are
      potential leads for the development of novel anti-cancer drugs. We then
      characterized the interaction patterns between ROCK1 and two inhibitors with
      novel scaffolds by molecular dynamics (MD) simulations and free energy
      decomposition analysis. In addition, the pharmacological effect of the two ROCK1
      inhibitors with novel scaffolds on atorvastatin-induced cerebral hemorrhage was
      evaluated by using zebrafish model, and one compound candidate is able to prevent
      atorvastatin-induced cerebral hemorrhage effectively.

PMID- 23549430
TI  - Capillary electrophoretic fingerprint investigation of gel pen inks.
AB  - In this study, two capillary electrophoresis modes, capillary zone
      electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC), were
      employed for the examination of gel ink fingerprints. The optimized CZE
      conditions were as follows: running buffer, 0.2M boric acid and 0.05M sodium
      tetraborate; pH, 6.47; detection, 214 nm; separation voltage, 20 kV MEKC
      conditions were as follows: 20 mM sodium tetraborate-20 mM sodium dodecyl
      sulphate; detection, 214 nm; separation voltage, 20 kV. The CZE and MEKC
      fingerprints of 18 el pen inks from Beijing markets were analyzed and the inks
      were classified according to the fingerprints of the two CE modes.

PMID- 23549431
TI  - Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis
      biobank samples.
AB  - BACKGROUND: The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA
      1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple
      sclerosis (MS) risk. Interaction between these two factors has been proposed.
      OBJECTIVES: The objective of this paper is to examine the association between
      antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS,
      and to examine if these antibodies and 25(OH)D status interact regarding MS risk
      in prospectively collected blood samples. METHODS: Antibody reactivity and
      25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched
      controls. The risk of MS was analysed using matched logistic regression.
      Interaction on the additive scale was assessed. RESULTS: The risk of MS increased
      across tertiles of antibody reactivity against EBNA-1, domain EBNA-1(402-502),
      and domain EBNA-1(385-420); p trends < 0.001. In young individuals (below median
      age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D
      levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1
      domains. No statistical interaction was found. CONCLUSIONS: We confirm that
      increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D
      status might influence the immune response towards Epstein-Barr virus in young
      subjects, and thereby modulate MS risk.

PMID- 23549432
TI  - Childhood body mass index and multiple sclerosis risk: a long-term cohort study.
AB  - BACKGROUND: Obesity in late adolescence has been associated with an increased
      risk of multiple sclerosis (MS); however, it is not known if body size in
      childhood is associated with MS risk. METHODS: Using a prospective design we
      examined whether body mass index (BMI) at ages 7-13 years was associated with MS
      risk among 302,043 individuals in the Copenhagen School Health Records Register
      (CSHRR). Linking the CSHRR with the Danish MS registry yielded 774 MS cases (501
      girls, 273 boys). We used Cox proportional hazards models to estimate the hazard
      ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among girls, at each
      age 7-13 years, a one-unit increase in BMI z-score was associated with an
      increased risk of MS (HR(age 7)=1.20, 95% CI: 1.10-1.30; HR(age 13)=1.18, 95% CI:
      1.08-1.28). Girls who were >=95(th) percentile for BMI had a 1.61-1.95-fold
      increased risk of MS as compared to girls <85(th) percentile. The associations
      were attenuated in boys. The pooled HR for a one-unit increase in BMI z-score at
      age 7 years was 1.17 (95% CI: 1.09-1.26) and at age 13 years was 1.15 (95% CI:
      1.07-1.24). CONCLUSION: Having a high BMI in early life is a risk factor for MS,
      but the mechanisms underlying the association remain to be elucidated.

PMID- 23549433
TI  - A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese.
AB  - BACKGROUND: The G allele of NOTCH4 rs422951 is protective against demyelinating
      disease in Japanese. OBJECTIVES: The purpose of this study was to assess the
      relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder
      (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and
      HLA-DRB1 alleles, and to clarify any association of the G allele with clinical
      features. METHODS: DNA sequencing was used to genotype 106 NMO/NMOSD patients,
      118 MS patients and 152 healthy controls (HCs) for rs422951. RESULTS: G allele
      frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that
      in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was
      positively associated with MS (OR=2.22, p(corr) =0.0380) while DRB1*0901 was
      negatively associated (OR=0.32, p(corr) =0.0114). Logistic regression analyses
      revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901,
      rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence
      interval (CI)= 0.20-0.66, p=0.0012). Haplotype analyses identified two
      susceptible and three resistant haplotypes formed from rs422951 and either HLA
      DRB1*0405 or DRB1*0901. There were no statistically significant differences in
      clinical features between G allele carriers and non-G allele carriers.
      CONCLUSION: This NOTCH4 missense mutation decreased the risk for developing MS in
      Japanese, but did not affect clinical features of those who had already developed
      the disease.

PMID- 23549434
TI  - Neuromyelitis optica in patients with coexisting human immunodeficiency virus
      infections.
AB  - Two patients with known human immunodeficiency virus (HIV) infections and
      receiving antiretroviral treatment developed neuromyelitis optica (Devic's
      disease). One patient tested positive for serum aquaporin-4 immunoglobulin G
      antibodies. Both patients were treated with high dose pulsed intravenous
      methylprednisolone followed by standard sessions of plasma exchange both at the
      onset attack and during disease relapses. For maintenance therapy, one patient
      received rituximab infusions and the second patient received mycophenolate
      mofetil orally. Despite treatment, both patients are currently wheelchair-bound
      due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV
      infection and poses an ongoing therapeutic challenge. 

PMID- 23549435
TI  - Refining response to treatment as defined by the Modified Rio Score.

PMID- 23549436
TI  - Some are more equal than others: the role of "keystone" species in the
      degradation of recalcitrant substrates.
AB  - The microbial communities found in the mammalian large intestine and rumen
      efficiently degrade many recalcitrant substrates that are resistant to the host's
      digestive enzymes. These communities are known from molecular profiling to be
      highly diverse at the species and strain level, but it may be that only certain
      specialized organisms ("keystone species") have the ability to initiate
      degradation of such substrates, thus releasing energy on which the rest of the
      community depends. We have recently reported that Ruminococcus bromii has a
      superior ability to degrade certain forms of particulate resistant starch (RS)
      when compared with other highly abundant species of amylolytic bacteria found in
      the human colon and have presented evidence that this bacterium provides an
      example of a keystone species within the microbial community with respect to RS
      fermentation. The concept of keystone species can be equally relevant to other
      activities, e.g., those involved in stabilizing the community.

PMID- 23549437
TI  - Mechanomyographic responses for the biceps brachii are unable to track the
      declines in peak torque during 25, 50, 75, and 100 fatiguing isokinetic muscle
      actions.
AB  - This study examined the peak torque and mechanomyographic (MMG) amplitude and
      mean frequency (MNF) responses during fatiguing isokinetic muscle actions. On
      four separate occasions, twenty men (mean +/- SD age = 23 +/- 3 years) performed
      25, 50, 75, and 100 repeated maximal concentric isokinetic muscle actions of the
      dominant forearm flexors. During each muscle action, the MMG signal was detected
      from the biceps brachii with an accelerometer. The data were examined with linear
      regression and one-way repeated measures analyses of variance. The results
      indicated that the mean percent decline in peak torque value for the 25
      repetition trial (25.6%) was significantly less than that for the 50 repetition
      trial (45.2%). Furthermore, the mean linear slope coefficient for the peak torque
      versus repetition number relationship for the 50 repetition trial was
      significantly less than that for the 100 repetition trial. There were no mean
      differences among the trials for the linear slope coefficients and y-intercepts
      for the MMG amplitude and MNF versus repetition number relationships. When
      detected with an accelerometer, the linear slope coefficients and y-intercepts
      for the MMG amplitude and MNF versus repetition number relationships were not
      sensitive enough to track the decline in muscle function during fatigue. 

PMID- 23549438
TI  - Molecular photoswitches based on spiro-acridans.
AB  - Thermally reversible photochromic spiro-acridans have been synthesized for the
      first time. They exhibit high ring opening efficiencies. As the formed
      zwitterions do not possess a merocyanine structure their lifetime is in the range
      of milliseconds to seconds. An observed side reaction can be avoided by suitable
      substitution of hydrogen atoms.

PMID- 23549439
TI  - International practice of laryngectomy rehabilitation interventions: a
      perspective from South Africa.
AB  - PURPOSE OF REVIEW: This review reflects on the experience of speech
      rehabilitation of laryngectomees at the Groote Schuur Hospital in Cape Town and
      expands on ways of dealing with the challenges that practising in a developing
      world setting presents. RECENT FINDINGS: Postlaryngectomy speech rehabilitation
      is unavailable in most African countries because of a profound shortage of speech
      and language therapists, otolaryngologists, and trained head and neck surgeons,
      as well as fiscal limitations. This article presents our recent tracheoesophageal
      speech results; discusses the employment of early postlaryngectomy feeding,
      selection criteria for patients for tracheoesophageal speech, the choice of voice
      prosthesis, follow-up care of patients coming from afar; and presents the results
      of a comparative study of the efficacy of different methods of airway
      humidification. SUMMARY: Our data and experience illustrate that excellent
      postlaryngectomy speech results can be achieved in a developing world setting by
      a dedicated team comprising speech and language therapists and otolaryngologists,
      that early postlaryngectomy feeding is well tolerated, and that a simple cotton
      cloth stoma cover is as effective as more expensive heat moisture exchange
      devices.

PMID- 23549440
TI  - Patient adherence to allergy immunotherapy.
AB  - PURPOSE OF REVIEW: This article reviews the literature on patient adherence to
      two different approaches to allergen-specific immunotherapy for allergic disease.
      Factors related to adherence in general, as well as the various methods used to
      measure adherence, will be discussed. RECENT FINDINGS: Although a complex
      interaction of factors related to both the physician and the patient influence
      the adherence to a particular therapeutic regimen, effective communication
      between these two parties and the simplicity of the regimen are frequently noted
      to be of primary importance. Variability with respect to the definition of
      adherence, the method of measuring adherence, and the length of the measuring
      period has resulted in a wide range of adherence rates to allergy immunotherapy
      reported in the literature. Patients most often site inconvenience, side-effects,
      and poor efficacy as reasons for discontinuing allergy immunotherapy. SUMMARY:
      Adherence to therapy not only improves individual patient outcomes, but also
      helps determine the best treatment modalities and reduces the burden of disease
      on society. As new methods of delivering immunotherapy are being developed, such
      as allergy immunotherapy tablets and oral mucosal immunotherapy, the factors
      associated with patient adherence should be carefully considered.

PMID- 23549441
TI  - Factors associated with self-perception of health among Brazilian women 50 years
      or older: a population-based study.
AB  - OBJECTIVE: The aim of this study was to evaluate factors associated with self
      perception of health among women 50 years or older living in a Brazilian city.
      METHODS: A cross-sectional, population-based study was conducted using self
      reported data from a household survey carried out in a sample of 622 women 50
      years or older. Sociodemographic and clinical factors associated with the women's
      perception of their own health (very good, good, fair, poor, or very poor) were
      assessed. chi2 test and Poison multiple logistic regression analysis were used to
      select the principal factors associated with a poorer perception of health at a
      significance level of 5%. RESULTS: Multiple analyses showed that the probability
      of association of chronic diseases with a woman's perception of her health as
      fair, poor, or very poor increased by 97% when at least two morbidities were
      present, whereas for each point (kg/m2) increase in body mass index, the
      probability of association with her perceiving her health as poorer increased by
      2% (95% CI, 1.01-1.04). The probability of association decreased by 50% if she
      had more than 8 years of schooling (95% CI, 0.36-0.70), by 29% if she had health
      insurance (95% CI, 0.59-0.86), and by 32% if she performed physical exercise
      weekly (95% CI, 0.54-0.86). CONCLUSIONS: The presence of multimorbidities and a
      higher body mass index increases the probability of association with a woman's
      poorer perception of her own health, whereas having more than 8 years of
      schooling, having medical insurance, and performing physical exercise weekly
      decreases the probability of association with a poorer perception of health.

PMID- 23549442
TI  - Blockade of substance P receptor attenuates osteoporotic pain, but not bone loss,
      in ovariectomized mice.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of a substance P
      (SP) receptor (NK1 receptor [NK1-R]) antagonist on hyperalgesia and bone
      metabolism in ovariectomized mice. METHODS: Thirty-six 9-week-old mice were
      subjected to either bilateral ovariectomy or sham surgery. Three weeks after the
      operation, the mice were treated with either a single-dose injection or 2-week
      repeated daily administration of L-703606, an NK1-R antagonist. Behavioral tests
      were performed for pain assessment; tibiae and the third lumbar vertebrae were
      dissected and assessed for microarchitectural or biomechanical properties. The
      expressions of SP and NK1-R in the dorsal root ganglia and spinal cord were also
      evaluated. RESULTS: Both single-dose injection and 2-week repeated injections of
      L-703606 led to a significant increase in nociceptive threshold in ovariectomized
      mice. However, the antihyperalgesic effect faded at 2 hours and almost
      disappeared at 5 hours after a single-dose injection. With the 14-day repeated
      treatment of ovariectomized mice, the effect was not detectable at 24 hours after
      the first injection but was obvious at 24 hours after 1-week and 2-week
      administrations and still existed at 48 hours after the last injection.
      Ovariectomized mice at the hyperalgesic state had enhanced SP immunoreactivity in
      the dorsal root ganglia and up-regulated SP and NK1-R expressions in the spinal
      cord. However, no significant change in serum SP level was detected. Two-week
      treatment with L-703606 could down-regulate these expressions but failed to
      salvage the deteriorated trabecular microstructure and reduced compressive
      strength in ovariectomized mice. CONCLUSIONS: Estrogen deficiency-induced
      hyperalgesia is achieved through up-regulation of SP and NK1-R expressions.
      Blockade of SP receptor can alleviate pain but cannot ameliorate bone loss. NK1-R
      antagonist is not recommended for the treatment of estrogen deficiency
      osteoporosis.

PMID- 23549443
TI  - More vasomotor symptoms in menopause among women with a history of hypertensive
      pregnancy diseases compared with women with normotensive pregnancies.
AB  - OBJECTIVE: Cardiovascular disease is the major cause of mortality in women
      worldwide. In recent years, several female-specific cardiovascular risk factors,
      such as hypertensive pregnancy diseases (HPDs) and vasomotor menopausal symptoms
      (VMS), have been identified. In this study, we evaluated the association between
      a history of HPD and the presence of VMS. METHODS: We consecutively included 853
      women (mean age, 55.5 y) who visited the outpatient cardiovascular clinic for
      women in Kampen between 2003 and 2010. The visit included a questionnaire on
      history of HPD, demographic characteristics, and VMS; physical examination; and
      blood sampling. Logistic regression analysis was used to analyze the data.
      RESULTS: A history of HPD was reported by 274 women (32%), and VMS were reported
      by 83% of women with a history of HPD and by 75% of women without a history of
      HPD. In adjusted models, VMS were more often present (odds ratio [OR], 1.62; 95%
      CI, 1.00-2.63) and more frequently persisted for longer than 1 year (OR, 2.05;
      95% CI, 1.08-3.89) among women with a history of HPD than among women with
      normotensive pregnancies. VMS were more often severe in women with a history of
      HPD, but this did not reach significance (adjusted OR, 1.28; 95% CI, 0.92-1.80).
      The frequency and intensity of VMS did not differ between both groups.
      CONCLUSIONS: In our "Kampen women cardiology clinic" cohort, women with a history
      of HPD report VMS during the menopausal transition significantly more often than
      women with normotensive pregnancies.

PMID- 23549444
TI  - Should new-onset arthralgia be considered a menopausal symptom?

PMID- 23549445
TI  - Aging, obesity, and multimorbidity in women 50 years or older: a population-based
      study.
AB  - OBJECTIVE: This study aims to evaluate multimorbidity and its associated factors
      in Brazilian women aged 50 years or older. METHODS: This is a cross-sectional,
      population-based study using self-reports. A total of 622 women aged 50 years or
      older were included. Multimorbidity was defined as two or more of the following
      morbidities: hypertension, osteoarthritis, cataracts, diabetes mellitus,
      osteoporosis, glaucoma, chronic bronchitis or asthma, urinary incontinence,
      cancer, myocardial infarction, stroke, and pulmonary emphysema. Sociodemographic,
      clinical, and behavioral factors were evaluated. Data were analyzed using chi
      test and Fisher's exact test, and Poisson multiple regression analysis was
      performed. Prevalence ratios and their 95% CIs were calculated. RESULTS: In this
      sample, 15.8% of participants reported no morbidities, whereas 26% reported
      having one morbid condition and 58.2% reported multimorbidity. With respect to
      morbidities, 55.9% of women reported having hypertension, 33.8% reported having
      osteoarthritis, 24.5% reported having cataracts, 22.7% reported having diabetes,
      21.3% reported having osteoporosis, 9.9% reported having glaucoma, 9.2% reported
      having bronchitis, 8.9% reported having urinary incontinence, and 6.8% reported
      having cancer, whereas 4.8% reported having had a myocardial infarction, 2.7%
      reported having had a stroke, and 1.8% reported having pulmonary emphysema.
      Multiple regression analysis showed that for each additional year of life, women
      increased their likelihood of multimorbidity by 3% (95% CI, 1.02-1.04).
      Furthermore, for each point increase (kg/m) in their body mass index, women also
      increased their likelihood of multimorbidity by 3% (95% CI, 1.02-1.04).
      CONCLUSIONS: Multimorbidity is principally associated with aging and obesity.

PMID- 23549446
TI  - Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN,
      and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women.
AB  - OBJECTIVE: The aim of our study was to investigate whether polymorphisms in
      microRNA machinery genes are associated with the risk of primary ovarian
      insufficiency (POI). METHODS: We genotyped 136 POI patients and 236 controls
      among Korean women for nine single nucleotide polymorphisms (SNPs; DROSHA
      rs6877842 and rs10719; DICER1 rs13078 and rs3742330; RAN rs14035; and XPO5
      rs34324334, rs2257082, rs11544382, and rs11077) by polymerase chain reaction
      restriction fragment length polymorphism analysis. Differences in genotype
      frequencies between patients and controls were compared, and odds ratios (ORs)
      and 95% CIs were determined as measures of the strength of the association
      between genotype and POI. RESULTS: Of the nine SNPs, XPO5 rs34324334 and
      rs11544382 were monomorphic and were not analyzed further. The XPO5 rs2257082 CT
      and CT + TT variant genotypes were more frequent in patients (OR, 2.097; 95% CI,
      1.207-3.645) than in controls (OR, 2.030; 95% CI, 1.196-3.445). The combined
      frequencies of XPO5 rs2257082 CT + TT and rs11077 AC + CC genotypes were higher
      in patients than in controls (OR, 2.526; 95% CI, 1.088-5.865). An association of
      POI risk with other polymorphisms was not found. A haplotype-based analysis of
      seven polymorphisms of the microRNA machinery genes for gene-gene interactions
      suggests that ***ACTA, ***GCCA, ***G*C*, *T*ATTA, and ***ACT* haplotypes
      (asterisk indicates SNP locus not included; DROSHA rs6877842 and rs10719, DICER1
      rs13078 and rs3742330, RAN rs14035, and XPO5 rs2257082 and rs11077 polymorphisms)
      are associated with higher POI prevalence, and that ***GCTA, ***ACCA, *C*ATTA,
      and *C*ATT* haplotypes are associated with lower POI prevalence. CONCLUSIONS: Our
      data demonstrate that the XPO5 rs2257082 T variant allele occurs more frequently
      in POI patients than in controls, suggesting that this allele may be associated
      with increased POI risk.

PMID- 23549447
TI  - Division of labor between lung dendritic cells and macrophages in the defense
      against pulmonary infections.
AB  - The lung is highly exposed to the external environment. For this reason, the lung
      needs to handle a number of potential threats present in inhaled air such as
      viruses or bacteria. Dendritic cells (DCs) and macrophages (MFs) play an
      important role in orchestrating the immune responses to these challenges. The
      severe lung inflammation caused by some pathogens poses a unique challenge to the
      immune system: the potential insult must be eliminated rapidly whereas tissue
      inflammation must be controlled in order to avoid collateral damages that can
      lead to acute respiratory failure. Immune responses to infectious agents are
      initiated and controlled by various populations of antigen-presenting cells with
      specialized functions, which include conventional DCs (cDCs), monocyte-derived
      DCs (moDCs), plasmacytoid DCs (pDCs), and alveolar MFs (AMFs). This review will
      discuss the role of these different cells in responses to pulmonary infections,
      with a focus on influenza virus and Mycobacterium tuberculosis.

PMID- 23549449
TI  - CD30L/CD30 is critical for maintenance of IL-17A-producing gammadelta T cells
      bearing Vgamma6 in mucosa-associated tissues in mice.
AB  - CD30 ligand (CD30L, CD153), a member of the tumor necrosis factor (TNF)
      superfamily, and its receptor CD30 are important for differentiation and
      activation of CD4(+) T helper type 17 (Th17) cells. In this report, we
      demonstrate that the interleukin 17A (IL-17A)-producing gammadelta T cells
      normally developed in the fetal thymus, whereas Vgamma1(-)Vgamma4(-) gammadelta T
      cells expressed Vgamma6/Vdelta1 gene transcript selectively decreased in mucosa
      associated tissues in naive CD30KO or CD30LKO mice. Moreover, CD30 and CD30L were
      expressed preferentially by Vgamma1(-)Vgamma4(-) gammadelta T cells in naive
      mice. The bacteria clearance was attenuated by the impaired response of the IL
      17A-producing gammadelta T cells and decreased infiltration of neutrophils in
      CD30KO or CD30LKO mice. In vivo administration of agonistic anti-CD30 monoclonal
      antibody restored the ability of protection against Listeria monocytogenes by
      enhancing Vgamma1(-)Vgamma4(-) gammadelta T cells producing IL-17A not only in
      wild-type but also CD30LKO mice. Taken together, it appears that CD30L/CD30
      signaling plays an important role in the maintenance and activation of IL-17A
      producing gammadelta T cells presumably bearing Vgamma6 in the mucosa-associated
      tissues of mice. 

PMID- 23549450
TI  - Switching kinetics of electrochemical metallization memory cells.
AB  - The strongly nonlinear switching kinetics of electrochemical metallization memory
      (ECM) cells are investigated using an advanced 1D simulation model. It is based
      on the electrochemical growth and dissolution of a Ag or Cu filament within a
      solid thin film and accounts for nucleation effects, charge transfer, and cation
      drift. The model predictions are consistent with experimental switching results
      of a time range of 12 orders of magnitude obtained from silver iodide (AgI) based
      ECM cells. By analyzing the simulation results the electrochemical processes
      limiting the switching kinetics are revealed. This study provides new insights
      into the understanding of the limiting electrochemical processes determining the
      switching kinetics of ECM cells.

PMID- 23549448
TI  - Mucosal immunity in human and simian immunodeficiency lentivirus infections.
AB  - Overwhelming evidence indicates that distinct pathological phenomenon occurs
      within the gastrointestinal (GI) tract of progressively simian immunodeficiency
      virus (SIV)-infected Asian macaques and HIV-infected humans compared with other
      anatomical sites. Massive loss of GI tract lamina propria CD4 T cells, alteration
      in the profile of lymphocytic cytokine production, changes in the landscape of GI
      tract antigen-presenting cells, and variations to the structural barrier of the
      GI tract are hallmarks of progressive HIV/SIV infections. The pathology within
      the GI tract results in translocation of microbial products from the lumen of the
      intestine into peripheral circulation. These translocated microbial products
      directly stimulate the immune system and exacerbate immune activation and, thus,
      disease progression. Initiation of combination antiretroviral therapy (cART) does
      not restore completely the immunological abnormalities within the GI tract. This
      incomplete restoration within the GI tract may contribute to the increased
      mortality observed within HIV-infected individuals treated for decades with cART.
      Novel therapeutic interventions aimed at enhancing GI tract anatomy and
      physiology may improve the prognosis of HIV-infected individuals.

PMID- 23549451
TI  - Drug self-administration studies: a novel reinforcement schedule enhances choice.
AB  - Relative reinforcing effects of different ethanol and different cocaine doses
      were studied under concurrent independent fixed-ratio (FR) schedules and
      concurrent nonindependent FR schedules with rhesus monkeys. Nonindependent FR
      schedules differed from independent FR schedules in that responses on either side
      counted towards the FR requirements of two concurrently presented choices. Thus,
      responses on the right operandum counted toward completion of both right and left
      FR schedules and, symmetrically, responses on the left did the same.
      Nonindependent schedules allow the number of responses per drug delivery to vary
      considerably, unlike independent schedules, thereby making the number of
      responses per delivery a sensitive dependent variable. In contrast, standard
      independent schedules do not allow responses per drug delivery to vary; the
      required number of responses is an independent variable. Three rhesus monkeys
      were subjects, and choices between different doses of ethanol or cocaine were
      studied. Larger doses maintained higher response rates than smaller doses -
      consistent with previous choice studies. By using nonindependent schedules,
      however, graded responses per drug delivery and increased switching between sides
      were obtained, providing additional data and useful measures of choice.

PMID- 23549452
TI  - Two-electron interference in a coherent beam.
AB  - The interference between quantum amplitude for two electrons, emitted from two
      source points, to be detected at two detection points, is a direct result of
      quantum exchange statistics. Such interference is observed in the coincidence
      probability, compared with that of statistically independent electrons, by
      computing the time correlation function from the arrival times of the electrons.
      When the two detectors are separated by a distance less than the coherence
      length, the coincidence probability is suppressed for electrons (antibunching)
      due to the Pauli principle, even though they do not interact with each other.
      However, electrons are charged particles. The Coulomb potential, which governs
      the scattering of one charged particle by another, is so long ranged. It is
      obvious that we must consider the Pauli principle and the Coulomb interactions
      simultaneously. This paper deals with basic experimental and theoretical
      investigations of the antibunching behavior of electrons in a free beam by
      considering the Pauli principle and the direct Coulomb interaction between two
      individual electrons. The experimentally found dependences are described in a
      model which considers the Coulomb scattering and theoretical values of
      correlation signals evaluated by analytical calculations agree with those
      determined by experiment. A study of the time correlation function from the
      arrival times of the electrons will lead to an understanding of the physical
      processes that take place in electron guns.

PMID- 23549453
TI  - The Aharanov-Bohm effect, magnetic monopoles and reversal in spin-ice lattices.
AB  - The proof of the Aharonov-Bohm (AB) effect has been one of the most important
      experiments of the last century and used as essential evidence for the theory of
      gauge fields. In this article, we look at its fundamental relation to the Dirac
      monopole and string. Despite the Dirac string being invisible to the AB effect,
      it can be used to study emergent quasiparticles in condensed matter settings that
      behave similar to the fundamental monopoles and strings between them. We utilize
      phase-imaging method based on the AB effect to study the ordering in a one-model
      system - that of frustrated spin ice - to understand the ordering processes that
      occur during a magnetic field reversal cycle. The reversal is linked to the
      propagation of monopole defects linked by flux channels, reminiscent of Dirac
      strings. Monopole interactions govern the defect densities within the lattice.
      Furthermore, we exploit these interactions to propose a new ordering method in
      which high degrees of ground-state ordering can be achieved in a frustrated
      system.

PMID- 23549454
TI  - Lorentz microscopy observation of vortices in high-Tc superconductors using a 1
      MV field emission transmission electron microscope.
AB  - Lorentz microscopy has opened the door to observing a single quantized magnetic
      flux line (i.e. a vortex) and its dynamic behavior inside a superconductor in
      real time. It resulted from the efforts of Dr Akira Tonomura and his
      collaborators, who developed a field emission electron microscope and advanced
      the technologies used for visualizing vortices (e.g. a low-temperature specimen
      stage and a magnetic-field application system). They used a 1-MV field emission
      transmission electron microscope with an electron beam that can penetrate thick
      specimens of high-temperature superconductors (Bi2Sr2CaCu2O8+delta and YB2C3O7
      delta) to reveal the flux-line features inside materials and their interactions
      with defects. This memorial paper reviews the results of research in the area of
      vortex matter physics.

PMID- 23549456
TI  - An alternately introduced heterometallo-supramolecular polymer: synthesis and
      solid-state emission switching by electrochemical redox.
AB  - By utilizing different coordination properties of a lanthanide ion and a
      transition metal ion, a heterometallo-supramolecular polymer with Eu(III) and
      Fe(II) ions introduced alternately (polyEuFe) was precisely prepared via stepwise
      complexation of the metal ions to a new unsymmetrical ligand with both a
      dicarboxylate-substituted terpyridine and an unsubstituted terpyridine. The
      polymer showed unique, reversible "on-off" switching of the Eu(III) luminescence
      by electrochemical redox of the Fe ions in the solid-state.

PMID- 23549457
TI  - Customizing laboratory mice by modifying gut microbiota and host immunity in an
      early "window of opportunity".
AB  - We recently investigated how post-natal microbial gut colonization is important
      for the development of the immune system, especially in the systemic
      compartments. This addendum presents additional data which in accordance with our
      previous findings show that early life microbial colonization is critical for a
      fine-tuned immune homeostasis to develop also in the intestinal environment. A
      generalized reduction in the expression of immune signaling related genes in the
      small intestine may explain previously shown increased systemic adaptive immune
      reactivity, if the regulatory cross-talk between intra- and extra-intestinal
      immune cells is immature following a neonatal germ-free period. These findings
      are furthermore discussed in the context of recently published results on how
      lack of microbial exposure in the neonatal life modifies disease expression in
      rodents used as models mimicking human inflammatory diseases. In particular, with
      a focus on how these interesting findings could be used to optimize the use of
      rodent models.

PMID- 23549458
TI  - CD44v6 expression in human skin keratinocytes as a possible mechanism for
      carcinogenesis associated with chronic arsenic exposure.
AB  - Inorganic arsenic is a well-known human skin carcinogen. Chronic arsenic exposure
      results in various types of human skin lesions, including squamous cell carcinoma
      (SCC). To investigate whether mutant stem cells participate in arsenic-associated
      carcinogenesis, we repeatedly exposed the HaCaT cells line to an environmentally
      relevant level of arsenic (0.05 ppm) in vitro for 18 weeks. Following sodium
      arsenic arsenite administration, cell cycle, colony-forming efficiency (CFE),
      cell tumorigenicity, and expression of CD44v6, NF-kappaB and p53, were analyzed
      at different time points (0, 5, 10, 15, 20, 25 and 30 passages). We found that a
      chronic exposure of HaCaT cells to a low level of arsenic induced a cancer stem-
      like phenotype. Furthermore, arsenic-treated HaCaT cells also became tumorigenic
      in nude mice, their growth cycle was predominantly in G2/M and S phases. Relative
      to nontreated cells, they exhibited a higher growth rate and a significant
      increase in CFE. Western blot analysis found that arsenic was capable of
      increasing cell proliferation and sprouting of cancer stem-like phenotype.
      Additionally, immunohistochemical analysis demonstrated that CD44v6 expression
      was up-regulated in HaCaT cells exposed to a low level of arsenic during early
      stages of induction. The expression of CD44v6 in arsenic-treated cells was
      positively correlated with their cloning efficiency in soft agar (r=0.949,
      P=0.01). Likewise, the expressions of activating transcription factor NF-kappaB
      and p53 genes in the arsenic-treated HaCaT cells were significantly higher than
      that in non-treated cells. Higher expressions of CD44v6, NF-kappaB and p53 were
      also observed in tumor tissues isolated from Balb/c nude mice. The present
      results suggest that CD44v6 may be a biomarker of arsenic-induced neoplastic
      transformation in human skin cells, and that arsenic promotes malignant
      transformation in human skin lesions through a NF-kappaB signaling pathway
      stimulated expression of CD44v6.

PMID- 23549459
TI  - Maxillary sinus augmentation procedures through equine-derived biomaterial or
      calvaria autologous bone: immunohistochemical evaluation of OPG/RANKL in humans.
AB  - Autologous bone is considered the gold standard for bone regeneration, even if
      different heterologous bone substitutes have been proposed to overcome the limits
      related to its use. The aim of this study was to analyze and to compare the
      molecular events switched on by autologous or heterologous bone graft insertion,
      focusing on TGFbeta1 expression and OPG/RANKL ratio, to analyze resorption
      process, and estimating graft vascularization, new bone tissue deposition and its
      mineralization, through VEGF, BSP and SPARC expression evaluation, respectively.
      Patients needing pre-prosthetic rehabilitation of the posterior maxilla were
      treated using an equine-derived biomaterial (Group 1) or calvaria autologous bone
      (Group 2), according to the morphology of the bone defect. Bone graft integration
      was evaluated on bone samples obtained from the treated areas at the moment of
      dental implant insertion, by morphological and immunohistochemical analyses for
      TGFbeta1, OPG, RANKL, VEGF, BSP, and SPARC expression. Morphological analysis
      shows the presence of biomaterial residual granules in Group 1, in parallel to a
      good integration between graft and host tissue. Moderate TGFbeta1 expression is
      seen in both Group 1 and Group 2. OPG/RANKL ratio appear higher in Group 1; VEGF
      expression appears very strong in Group 1 and strong in Group 2, while BSP and
      SPARC expression results weak in Group 1 and moderate in Group 2. Results reveal
      the good integration between both types of graft and the host tissue, even though
      autologous graft seems to produce a faster regenerative process, as evidenced by
      the different expression of the investigated molecules. According to these
      observations, the clinical use of heterologous particulate equine-derived
      biomaterial may ensure long-term predictability of implant-prosthetic
      rehabilitation, comparable to that obtained with autologous bone graft.

PMID- 23549460
TI  - Excitatory amino acid transporter 5 is widely expressed in peripheral tissues.
AB  - It is routinely stated in the literature that Excitatory Amino Acid Transporter 5
      (EAAT5) is a retina-specific glutamate transporter. EAAT5 is expressed by retinal
      photoreceptors and bipolar cells, where it serves as a slow transporter and as an
      inhibitory glutamate receptor, the latter role is due to the gating of a large
      chloride conductance. The dogma of an exclusively retinal distribution has arisen
      because Northern blot analyses have previously shown only modest hybridisation in
      non-retinal tissues. Others have re-interpreted this as indicating that EAAT5 was
      only present in retinal tissues. However, this view appears to be erroneous;
      recent evidence demonstrating abundant expression of EAAT5 in rat testis prompted
      us to re-examine this dogma. A new antibody was developed to an intracellular
      loop region of rat EAAT5. This new tool, in concert with RT-PCR and sequencing,
      demonstrated that EAAT5 is widely distributed at the mRNA and protein levels in
      many non-nervous tissues including liver, kidney, intestine, heart, lung, and
      skeletal muscle. We conclude that EAAT5 is a widely distributed protein. Whether
      it functions in all locations as a glutamate transporter, or mainly as a
      glutamate-gated chloride conductance, remains to be determined.

PMID- 23549461
TI  - Immunological detection of m- and u-calpains in the skeletal muscle of
      Marchigiana cattle.
AB  - Calpains are Ca(2+)-dependent proteases able to cleave a large number of proteins
      involved in many biological functions. Particularly, in skeletal muscle they are
      involved in meat tenderizing during post mortem storage. In this report we
      analyzed the presence and expression of u- and m-calpains in two skeletal muscles
      of the Marchigiana cattle soon after slaughter, using immunocytochemical and
      immunohistochemical techniques, Western blotting analysis and Casein Zymography.
      Therefore, the presence and the activity of these proteases was investigated
      until 15th day post-mortem during normal process of meat tenderizing. The results
      showed m- and u-calpain immunosignals in the cytoplasm both along the Z disk/I
      band regions and in the form of intracellular stores. Moreover, the expression
      level of u-calpain but not m-calpain decreased after 10 days of storage. Such a
      decrease in u-calpain was accompanied by a gradual reduction of activity. On the
      contrary, m-calpain activity persisted up to 15 days of post-mortem storage. Such
      data indicate that expression and activity of both u-calpain and m-calpain
      analyzed in the Marchigiana cattle persist longer than reported in literature for
      other bovines and may be related to both the type of muscle and breed examined.

PMID- 23549462
TI  - The anti-inflammatory effects of exercise training promote atherosclerotic plaque
      stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis.
AB  - Physical exercise is the cornerstone of cardiovascular disease treatment. The
      present study investigated whether exercise training affects atherosclerotic
      plaque composition through the modification of inflammatory-related pathways in
      apolipoprotein E knockout (apoE(-/-)) mice with diabetic atherosclerosis. Forty
      five male apoE(-/-) mice were randomized into three equivalent (n=15) groups:
      control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by
      streptozotocin administration. High-fat diet was administered to all groups for
      12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise
      groups continued high-fat diet for 6 additional weeks. Exercising mice followed
      an exercise program on motorized-treadmill (5 times/week, 60 min/session). Then,
      blood samples and atherosclerotic plaques in the aortic root were examined. A
      considerable (P<0.001) regression of the atherosclerotic lesions was observed in
      the exercise group (180.339 +/- 75.613 x10(3)MUm(2)) compared to the control
      (325.485 +/- 72.302 x10(3)MUm(2)) and sedentary (340.188 +/- 159.108 x
      10(3)MUm(2)) groups. We found decreased macrophages, matrix metalloproteinase-2
      (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the
      atherosclerotic plaques of the exercise group. Compared to both control and
      sedentary groups, exercise training significantly increased collagen (P<0.05),
      elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2)
      (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with
      increased fibrous cap thickness and less internal elastic lamina ruptures after
      exercise training (P<0.05), while body-weight and lipid parameters did not
      significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic
      tissues followed a similar trend. From our study we can conclude that exercise
      training reduces and stabilizes atherosclerotic lesions in apoE-/- mice with
      diabetic atherosclerosis. A favorable modification of the inflammatory regulators
      seems to explain those beneficial effects.

PMID- 23549463
TI  - Decellularized omentum as novel biologic scaffold for reconstructive surgery and
      regenerative medicine.
AB  - Homologous tissues, such as adipose tissue, may be an interesting source of
      acellular scaffolds, maintaining a complex physiological three-dimensional (3D)
      structure, to be recellularized with autologous cells. The aim of the present
      work is to evaluate the possibility of obtaining homologous acellular scaffolds
      from decellularization of the omentum, which is known to have a complex vascular
      network. Adult rat and human omenta were treated with an adapted
      decellularization protocol involving mechanical rupture (freeze-thaw cycles),
      enzymatic digestion (trypsin, lipase, deoxyribonuclease, ribonuclease) and lipid
      extraction (2-propanol). Histological staining confirmed the effectiveness of
      decellularization, resulting in cell-free scaffolds with no residual cells in the
      matrix. The complex 3D networks of collagen (azan-Mallory), elastic fibers (Van
      Gieson), reticular fibers and glycosaminoglycans (PAS) were maintained, whereas
      Oil Red and Sudan stains showed the loss of lipids in the decellularized tissue.
      The vascular structures in the tissue were still visible, with preservation of
      collagen and elastic wall components and loss of endothelial (anti-CD31 and -CD34
      immunohistochemistry) and smooth muscle (anti-alpha smooth muscle actin) cells.
      Fat-rich and well vascularized omental tissue may be decellularized to obtain
      complex 3D scaffolds preserving tissue architecture potentially suitable for
      recellularization. Further analyses are necessary to verify the possibility of
      recolonization of the scaffold by adipose-derived stem cells in vitro and then in
      vivo after re-implantation, as already known for homologus implants in
      regenerative processes.

PMID- 23549464
TI  - Histochemical approaches to assess cell-to-cell transmission of misfolded
      proteins in neurodegenerative diseases.
AB  - Formation, aggregation and transmission of abnormal proteins are common features
      in neurodegenerative disorders including Parkinson's disease, Alzheimer's
      disease, amyotrophic lateral sclerosis, and Huntington's disease. The mechanisms
      underlying protein alterations in neurodegenerative diseases remain
      controversial. Novel findings highlighted altered protein clearing systems as
      common biochemical pathways which generate protein misfolding, which in turn
      causes protein aggregation and protein spreading. In fact, proteinaceous
      aggregates are prone to cell-to-cell propagation. This is reminiscent of what
      happens in prion disorders, where the prion protein misfolds thus forming
      aggregates which spread to neighbouring cells. For this reason, the term
      prionoids is currently used to emphasize how several misfolded proteins are
      transmitted in neurodegenerative diseases following this prion-like pattern.
      Histochemical techniques including the use of specific antibodies covering both
      light and electron microscopy offer a powerful tool to describe these phenomena
      and investigate specific molecular steps. These include: prion like protein
      alterations; glycation of prion-like altered proteins to form advanced glycation
      end-products (AGEs); mechanisms of extracellular secretion; interaction of AGEs
      with specific receptors placed on neighbouring cells (RAGEs). The present
      manuscript comments on these phenomena aimed to provide a consistent scenario of
      the available histochemical approaches to dissect each specific step.

PMID- 23549465
TI  - IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an
      immunohistochemical study.
AB  - The protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an
      important factor for cell migration and adhesion in malignancies. Recent studies
      have shown a remarkable overexpression of IMP3 in different human malignant
      neoplasms and also revealed it as an important prognostic marker in some tumor
      entities. The purpose of this study is to compare IMP3 immunostaining in squamous
      cellular skin tumor and determine whether IMP3 can aid in the differential
      diagnosis of these lesions. To our knowledge, IMP3 expression has not been
      investigated in skin squamous cell proliferations thus far. Immunohistochemical
      staining for IMP3 was performed on slides organized by samples from 67 patients,
      34 with keratoacanthoma and 33 with primary squamous cell carcinoma (16 invasive
      and 17 in situ). The majority of our KAs (25/34) were negative for IMP-3
      staining. The majority of SCCs (19/33) are positive for IMP3 staining. The
      percentage of IMP3 positive cells increases significantly in group SCC
      (p=0.0111), and in particular in the SCC in situ group (p=0.0021) with respect to
      the KA group.  IMP3 intensity staining increases significantly in SCCs
      (p=0.0213), and particularly in SCCs (p=0.008) with respect to KA. Our data show
      that IMP3 expression is different in keratoacanthomas with respect to squamous
      cell carcinoma. IMP3 assessment and staining pattern, together with a careful
      histological study, can be useful in the differential diagnosis between KA e SCC.

PMID- 23549466
TI  - Expression patterns of alpha2,3-sialyltransferase I and alpha2,6
      sialyltransferase I in human cutaneous epithelial lesions.
AB  - Skin tumors have become one of the most common cancers in the world and their
      carcinogenesis is frequently associated with altered glycosylation patterns. The
      aberrant sialylation, a type of glycosylation, can mediate pathophysiological key
      events during various stages of tumor progression, including invasion and
      metastasis. Sialyltransferases play a key role in a variety of biological
      processes, including cell-cell communication, cell-matrix interaction, adhesion,
      and protein targeting. In this study, it was evaluated the expression of ST3Gal I
      and ST6Gal I in cutaneous epithelial lesions that include actinic keratosis
      (n=15), keratoacanthoma (n=9), squamous cell carcinoma (n=22) and basal cell
      carcinoma (n=28) in order to evaluate if sialyltransferases expression is
      different in premalignant and in malignant tumors. The expression of ST3Gal I was
      observed in actinic keratosis (53%), keratoacanthoma (78%), squamous cell
      carcinoma (73%) and basal cell carcinoma (32%) with statistic differences between
      basal cell carcinoma and keratoacanthoma (P=0.0239) and basal cell carcinoma and
      squamous cell carcinoma (P=0.0096); for ST6Gal I, cytoplasmic expression was
      noted in actinic keratosis (40%), heterogeneous and cytoplasmic expression was
      noted in keratoacanthoma (67%), squamous cell carcinoma (41%) and basal cell
      carcinoma (7%) with statistic differences between basal cell carcinoma and
      squamous cell carcinoma (P=0.0061) and basal cell carcinoma and keratoacanthoma
      (P=0.0008). In summary, our results showed that the high expression of ST3Gal I
      and ST6Gal I, in skin tumors, is associated with tumors with greater potential
      for invasion and metastasis, as in the case of squamous cell carcinoma, and this
      may be related to their behavior.

PMID- 23549467
TI  - Expression of 8-OHdG in Zosterisessor ophiocephalus from the Venetian lagoon,
      Italy.
AB  - The aim of the present work was to evaluate the expression of 8-OHdG (8
      hydroxydeoxyguanosine) in the benthic fish Zosterisessor ophiocephalus collected
      in two differently polluted sites of the Venetian lagoon (Porto Marghera and
      Caroman). We compared our data on 8-OHdG with those of CYP1A (Cytochrome P450,
      family 1, subfamily A, polypeptide 1), which is a well known biomarker for
      detoxification of contaminants. Immunohistochemistry with an antibody to 8-OHdG
      showed immunopositivity in nuclei of hepatocytes as well as in melanomacrophage
      centres of spleen and kidney, whereas an anti-CYP1A antibody exhibited positive
      immunostaining in the liver, kidney and ovary. The liver of males showed higher
      expression of both proteins than females. In animals from Porto Marghera site,
      the enzymatic assay for 8-OHdG exhibited higher levels in liver of males than in
      females. Western Blot analysis using the antibody anti-CYP1A recognized the
      presence of a band of about 60 kDa in the liver of males and females. Males
      exhibited a strong band, whereas in females the band showed a lower intensity. By
      using Real-Time PCR, the mRNA expression of CYP1A did not show any differences
      between males and females from each site, but it was at borderline significance
      level. Comparing the two sites, mRNA expression of CYP1A was significantly higher
      in the liver of both males and females from Porto Marghera than that of Caroman.
      The present data suggest that pollutants are bio-available as demonstrated by our
      biomarker analyses and may have a harmful effect on aquatic organisms such as Z.
      ophiocephalus. We report that the highest levels of hepatic 8-OHdG and CYP1A
      expression were detected in males, showing clear gender specificity.

PMID- 23549468
TI  - Immunohistochemical study of doublecortin and nucleostemin in canine brain.
AB  - Finding a marker of neural stem cells remains a medical research priority. It was
      reported that the proteins doublecortin and nucleostemin were related with
      stem/progenitor cells in central nervous system. The aim of the present
      immunohistochemical study was to evaluate the expression of these proteins and
      their pattern of distribution in canine brain, including age-related changes, and
      in non-nervous tissues. We found that doublecortin had a more specific expression
      pattern, related with neurogenesis and neuronal migration, while nucleostemin was
      expressed in most cells of almost every tissue studied. The immunolabeling of
      both proteins decreased with age. We may conclude that nucleostemin is not a
      specific marker of stem/progenitor cells in the dog. Doublecortin, however, is
      not an exclusive marker of neural stem cells, but also of neuronal precursors.

PMID- 23549473
TI  - Testicular germ cell tumors: biology and clinical update.
AB  - PURPOSE OF REVIEW: To discuss several important developments in the diagnosis,
      management, and risk stratification of testicular germ cell tumors (TGCTs) in the
      past year. RECENT FINDINGS: Germ cell function and tumorigenesis may be
      influenced by exposure to a variety of agents, including metals and cannabinoids.
      Genome-wide association studies have identified variants in several genes that
      may produce susceptibility to the development of testicular malignancies, and
      expression of certain proteins predicts a poorer prognosis and may, thus, play a
      role in neoplastic progression. Retroperitoneal lymph node dissection continues
      to play a crucial role in definitive treatment of patients with nonseminoma germ
      cell tumor, whereas radiotherapy, as a standard treatment for early-stage
      seminoma, has been declining due both to the efficacy of platinum-based
      chemotherapy and to the increased risk of radiation-related secondary
      malignancies. Advanced and platinum-refractory disease states continue to be
      challenging entities in terms of optimizing therapy and outcome. SUMMARY:
      Preclinical and clinical studies continue to enhance our insights into the
      complex biology of TGCTs, and are helping to further refine risk stratification
      and optimize treatment of patients with TGCTs.

PMID- 23549474
TI  - Bibliography. Head and neck. Current world literature.

PMID- 23549478
TI  - Nurses' day is every day!

PMID- 23549479
TI  - Temporal system-level organization of the switch from glycolytic to gluconeogenic
      operation in yeast.
AB  - The diauxic shift in Saccharomyces cerevisiae is an ideal model to study how
      eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic
      operation. In this work, we generated time-resolved physiological data,
      quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes)
      profiles. We found that the diauxic shift is accomplished by three key events
      that are temporally organized: (i) a reduction in the glycolytic flux and the
      production of storage compounds before glucose depletion, mediated by
      downregulation of phosphofructokinase and pyruvate kinase reactions; (ii) upon
      glucose exhaustion, the reversion of carbon flow through glycolysis and onset of
      the glyoxylate cycle operation triggered by an increased expression of the
      enzymes that catalyze the malate synthase and cytosolic citrate synthase
      reactions; and (iii) in the later stages of the adaptation, the shutting down of
      the pentose phosphate pathway with a change in NADPH regeneration. Moreover, we
      identified the transcription factors associated with the observed changes in
      protein abundances. Taken together, our results represent an important
      contribution toward a systems-level understanding of how this adaptation is
      realized.

PMID- 23549480
TI  - SH3 interactome conserves general function over specific form.
AB  - Src homology 3 (SH3) domains bind peptides to mediate protein-protein
      interactions that assemble and regulate dynamic biological processes. We surveyed
      the repertoire of SH3 binding specificity using peptide phage display in a
      metazoan, the worm Caenorhabditis elegans, and discovered that it structurally
      mirrors that of the budding yeast Saccharomyces cerevisiae. We then mapped the
      worm SH3 interactome using stringent yeast two-hybrid and compared it with the
      equivalent map for yeast. We found that the worm SH3 interactome resembles the
      analogous yeast network because it is significantly enriched for proteins with
      roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions
      are highly rewired. Our results suggest a model of network evolution where
      general function of the SH3 domain network is conserved over its specific form.

PMID- 23549481
TI  - Dissecting the energy metabolism in Mycoplasma pneumoniae through genome-scale
      metabolic modeling.
AB  - Mycoplasma pneumoniae, a threatening pathogen with a minimal genome, is a model
      organism for bacterial systems biology for which substantial experimental
      information is available. With the goal of understanding the complex interactions
      underlying its metabolism, we analyzed and characterized the metabolic network of
      M. pneumoniae in great detail, integrating data from different omics analyses
      under a range of conditions into a constraint-based model backbone. Iterating
      model predictions, hypothesis generation, experimental testing, and model
      refinement, we accurately curated the network and quantitatively explored the
      energy metabolism. In contrast to other bacteria, M. pneumoniae uses most of its
      energy for maintenance tasks instead of growth. We show that in highly linear
      networks the prediction of flux distributions for different growth times allows
      analysis of time-dependent changes, albeit using a static model. By performing an
      in silico knock-out study as well as analyzing flux distributions in single and
      double mutant phenotypes, we demonstrated that the model accurately represents
      the metabolism of M. pneumoniae. The experimentally validated model provides a
      solid basis for understanding its metabolic regulatory mechanisms.

PMID- 23549484
TI  - Thermal oxidation of Ni films for p-type thin-film transistors.
AB  - p-Type nanocrystal NiO-based thin-film transistors (TFTs) are fabricated by
      simply oxidizing thin Ni films at temperatures as low as 400  degrees C. The
      highest field-effect mobility in a linear region and the current on-off ratio are
      found to be 5.2 cm(2) V(-1) s(-1) and 2.2 * 10(3), respectively. X-ray
      diffraction, transmission electron microscopy and electrical performances of the
      TFTs with "top contact" and "bottom contact" channels suggest that the upper
      parts of the Ni films are clearly oxidized. In contrast, the lower parts in
      contact with the gate dielectric are partially oxidized to form a quasi
      discontinuous Ni layer, which does not fully shield the gate electric field, but
      still conduct the source and drain current. This simple method for producing p
      type TFTs may be promising for the next-generation oxide-based electronic
      applications.

PMID- 23549482
TI  - Plant stem cell maintenance involves direct transcriptional repression of
      differentiation program.
AB  - In animal systems, master regulatory transcription factors (TFs) mediate stem
      cell maintenance through a direct transcriptional repression of differentiation
      promoting TFs. Whether similar mechanisms operate in plants is not known. In
      plants, shoot apical meristems serve as reservoirs of stem cells that provide
      cells for all above ground organs. WUSCHEL, a homeodomain TF produced in cells of
      the niche, migrates into adjacent cells where it specifies stem cells. Through
      high-resolution genomic analysis, we show that WUSCHEL represses a large number
      of genes that are expressed in differentiating cells including a group of
      differentiation promoting TFs involved in leaf development. We show that WUS
      directly binds to the regulatory regions of differentiation promoting TFs;
      KANADI1, KANADI2, ASYMMETRICLEAVES2 and YABBY3 to repress their expression.
      Predictions from a computational model, supported by live imaging, reveal that
      WUS-mediated repression prevents premature differentiation of stem cell
      progenitors, being part of a minimal regulatory network for meristem maintenance.
      Our work shows that direct transcriptional repression of differentiation
      promoting TFs is an evolutionarily conserved logic for stem cell regulation.

PMID- 23549483
TI  - Construction of human activity-based phosphorylation networks.
AB  - The landscape of human phosphorylation networks has not been systematically
      explored, representing vast, unchartered territories within cellular signaling
      networks. Although a large number of in vivo phosphorylated residues have been
      identified by mass spectrometry (MS)-based approaches, assigning the upstream
      kinases to these residues requires biochemical analysis of kinase-substrate
      relationships (KSRs). Here, we developed a new strategy, called CEASAR, based on
      functional protein microarrays and bioinformatics to experimentally identify
      substrates for 289 unique kinases, resulting in 3656 high-quality KSRs. We then
      generated consensus phosphorylation motifs for each of the kinases and integrated
      this information, along with information about in vivo phosphorylation sites
      determined by MS, to construct a high-resolution map of phosphorylation networks
      that connects 230 kinases to 2591 in vivo phosphorylation sites in 652
      substrates. The value of this data set is demonstrated through the discovery of a
      new role for PKA downstream of Btk (Bruton's tyrosine kinase) during B-cell
      receptor signaling. Overall, these studies provide global insights into kinase
      mediated signaling pathways and promise to advance our understanding of cellular
      signaling processes in humans.

PMID- 23549485
TI  - Soluble P-selectin level correlates with acetylsalicylic acid but not with
      clopidogrel response in patients with stable coronary artery disease after a
      percutaneous coronary intervention.
AB  - BACKGROUND: Impaired response to dual antiplatelet therapy is associated with
      worse cardiovascular outcome. Besides antiplatelet effects, there is evidence
      that both clopidogrel and acetylsalicylic acid (ASA) have anti-inflammatory
      properties. However, little is known about the relationship between platelet
      function and inflammation under dual antiplatelet therapy in patients with stable
      coronary artery disease. PURPOSE: The purpose of the study was to investigate the
      correlation of platelet function with soluble (s)P-selectin and soluble (s)CD40L
      in patients undergoing elective percutaneous coronary intervention. Poor response
      to ASA and clopidogrel could lead to increased levels of inflammatory markers.
      METHODS: A total of 148 patients were included. Eighty percent of the patients
      were on 100 mg ASA and all patients were clopidogrel naive. They underwent
      percutaneous coronary intervention and received a loading dose of 600 mg
      clopidogrel. Platelet function was assessed by light transmittance aggregometry
      (LTA) and vasodilator-stimulated phosphoprotein analysis at baseline, 24 h after
      loading, and after 1 month of maintenance therapy, respectively. Plasma levels of
      sP-selectin and sCD40L were measured. To classify low responders to clopidogrel,
      patients were screened for genetic variants determining clopidogrel absorption
      and metabolization. RESULTS: sP-selectin levels correlated with LTA findings
      after stimulation with arachidonic acid (P=0.012). Further, in addition to
      decreased platelet reactivity observed on LTA, lower sP-selectin levels were seen
      in patients under ASA therapy (P=0.004). CYP2C19*2 allele carriers had a higher
      platelet reactivity after clopidogrel loading measured by adenosine diphosphate
      induced aggregation in LTA (P=0.008) and vasodilator-stimulated phosphoprotein
      phosphorylation (P=0.035); however, there was no difference in the inflammatory
      markers. Multiple regression analysis showed that variables significantly related
      to sP-selectin plasma levels were sCD40L (P<0.001), LTA after stimulation with
      arachidonic acid (P<0.001), adenosine diphosphate (20 umol/l, P=0.009), collagen
      (P<0.001), and ejection fraction (P=0.001). CONCLUSION: sP-selectin was decreased
      in patients receiving ASA but did not reflect a CYP2C19*2-defined clopidogrel
      response. This underlines that sP-selectin is a useful marker for ASA, but not
      for clopidogrel response, in stable coronary artery disease.

PMID- 23549486
TI  - High performance proton exchange membranes obtained by adjusting the distribution
      and content of sulfonic acid side groups.
AB  - The proton conductivity and oxidation resistance as well as dimensional stability
      of hydrocarbon proton exchange membranes were simultaneously improved, achieving
      exciting overall properties.

PMID- 23549487
TI  - Invasive thoughts: change or die!

PMID- 23549488
TI  - The impact of previous revascularization on clinical outcomes in patients
      undergoing primary percutaneous coronary intervention.
AB  - While the impact of prior coronary artery bypass graft surgery (CABG) on in
      hospital outcomes in patients with ST-elevation myocardial infarction (STEMI) has
      been described, data are limited on patients with prior percutaneous coronary
      intervention (PCI) undergoing primary PCI in the setting of an STEMI. The aim of
      the present study was to assess the effect of previous revascularization on in
      hospital outcomes in STEMI patients undergoing primary PCI. Between January 2004
      and December 2007, a total of 1649 patients underwent primary PCI for STEMI at
      four New York State hospitals. Baseline clinical and angiographic characteristics
      and in-hospital outcomes were prospectively collected as part of the New York
      State PCI Reporting System (PCIRS). Patients with prior surgical or percutaneous
      coronary revascularization were compared to those without prior coronary
      revascularization. Of the 1649 patients presenting with STEMI, a total of 93
      (5.6%) had prior CABG, 258 (15.7%) had prior PCI, and 1298 (78.7%) had no history
      of prior coronary revascularization. Patients with prior CABG were significantly
      older and had higher rates of peripheral vascular disease, diabetes mellitus,
      congestive heart failure, and prior stroke. Additionally, compared with those
      patients with a history of prior PCI as well as those without prior coronary
      revascularization, patients with previous CABG had more left main interventions
      (24% vs 2% and 2%; P<.001), but were less often treated with drug-eluting stents
      (47% vs 61% and 72%; P<.001). Despite a low incidence of adverse in-hospital
      events, prior CABG was associated with higher all-cause in-hospital mortality
      (6.5% vs 2.2%; P=.012), and as a result, higher overall MACE (6.5% vs 2.7%;
      P=.039). By multivariate analysis, prior CABG (odds ratio, 3.40; 95% confidence
      interval, 1.15-10.00) was independently associated with in-hospital mortality. In
      contrast, patients with prior PCI had similar rates of MACE (4.3% vs 2.7%; P=.18)
      and in-hospital mortality (3.1% vs 2.2%; P=.4) when compared to the de novo
      population. Patients with a prior history of CABG, but not prior PCI, undergoing
      primary PCI in the setting of STEMI have significantly worse in-hospital outcomes
      when compared with patients who had no prior history of coronary artery
      revascularization. Thus, only prior surgical - and not percutaneous -
      revascularization should be considered a significant risk factor in the setting
      of primary PCI.

PMID- 23549490
TI  - Magnetic navigation system and CT roadmap-assisted percutaneous coronary
      intervention: a comparison to the conventional approach.
AB  - BACKGROUND: Computed tomography coronary angiography (CTCA) has been successfully
      integrated with the magnetic navigation system (MNS) to facilitate a roadmap
      assisted percutaneous coronary intervention (PCI). The aim of this study was to
      compare this new approach of PCI versus conventional PCI regarding the difference
      of contrast usage, x-ray exposure, procedure success, and in-hospital expenses.
      METHODS: Thirty-eight patients with stable coronary artery disease and coronary
      artery lesions of >=70% diameter stenosis diagnosed by both pre-procedure CTCA
      and coronary angiography (CAG) were enrolled to receive the MNS and CT roadmap
      assisted PCI. Another 38 patients were consecutively recruited to receive
      conventional PCI, matched with the MNS group by the vessel and lesion type base
      on American College of Cardiology/American Heart Association criteria. RESULTS:
      Regarding the process of the guidewire placement, wherein the technical
      difference of the two procedures exists, the median contrast usage for guidewire
      crossing was significantly lower in the MNS group than in the conventional group
      [0.0 mL (interquartile range [IQR], 0.0-3.0 mL) vs 5.0 mL (IQR, 3.1-6.8 mL);
      P<.001], with zero contrast usage in 25 of the 44 guidewire placements in the MNS
      group, but in none of the conventional group; the radiation dosage for guidewire
      crossing in the MNS group was also significantly lower than in the conventional
      group (235.8 MUGym2 [IQR, 134.9-455.1 MUGym2] vs 364.4 MUGym2 [IQR, 223.4-547.2
      MUGym2]; P=.033). There were no significant differences between the two groups
      concerning the total contrast usage, total radiation dosage of the PCI, the
      procedural fees, or the overall in-hospital expenses. All of the enrolled vessels
      were successfully intervened in both groups. CONCLUSION: In PCI of simple
      lesions, the application of CT guidance and magnetic navigation had modest
      impacts on radiation dosage and contrast usage for wire crossing, but no impact
      on overall radiation dosage or contrast usage for the procedure. In addition, the
      use of CT roadmap and MNS was likely more expensive compared to PCI using
      conventional radiographic technique.

PMID- 23549489
TI  - In-hospital management and outcome of patients on warfarin undergoing coronary
      stent implantation: results of the multicenter, prospective WARfarin and coronary
      STENTing (WAR-STENT) registry.
AB  - The in-hospital management of patients on warfarin undergoing coronary stent
      implantation (PCI-S) is variable, and the in-hospital outcome incompletely
      defined. To determine the adherence to the current recommendations, and the
      incidence of adverse events, we carried out the prospective, multicenter,
      observational WARfarin and coronary STENTing (WAR-STENT) registry
      (ClinicalTrials.gov identifier NCT00722319). All consecutive patients on warfarin
      undergoing PCI-S at 37 Italian centers were enrolled and followed for 12 months.
      Outcome measures were: major adverse cardiovascular events (MACE), including
      cardiovascular death, non-fatal myocardial infarction, need for urgent
      revascularization, stroke, and venous thromboembolism, and major and minor
      bleeding. In this paper, we report the in-hospital findings. Out of the 411
      patients enrolled, 92% were at non-low (ie, moderate or high) thromboembolic
      risk. The radial approach and bare-metal stents were used in 61% and 60% of
      cases, respectively. Drug-eluting stents were essentially reserved to patients
      with diabetes, which in turn, significantly predicted the implantation of drug
      eluting stents (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.29-3.17;
      P=.002). The in-hospital MACE and major bleeding rates were 2.7% and 2.1%,
      respectively. At discharge, triple therapy (TT) of warfarin, aspirin, and
      clopidogrel was prescribed to 76% of patients. Prescription of TT was
      significantly more frequent in the non-low thromboembolic risk group. Non-low
      thromboembolic risk, in turn, was a significant predictor of TT prescription (OR,
      11.2; 95% CI, 4.83-26.3; P<.0001). In conclusion, real-world warfarin patients
      undergoing PCI-S are largely managed according to the current recommendations. As
      a consequence, the risk of in-hospital MACE and major bleedings appears limited
      and acceptable.

PMID- 23549491
TI  - A real all-comers randomized trial comparing Xience Prime and Promus Element
      stents.
AB  - BACKGROUND: The cobalt chromium everolimus-eluting stent (CoCr-EES) has shown the
      best safety and efficacy profile in the trials conducted so far. Recently, a new
      EES with a platinum-based platform (PtCr-EES) has been introduced in the market.
      There is only one study comparing both stents, but with important exclusion
      criteria. OBJECTIVES: We sought to evaluate clinical outcomes with the PtCr-EES
      compared with the CoCr-EES in an all-comers population. We have conducted a
      randomized all-comers study aimed to compare these stents in a real-practice
      scenario. METHODS: A total of 300 patients undergoing revascularization and
      suitable for long-term dual-antiplatelet therapy were randomized 1:1 to CoCr-EES
      or PtCr-EES. No exclusion criteria based on clinical presentation or lesion
      characteristics were applied. RESULTS: The clinical and angiographic
      characteristics were well balanced in both groups without significant
      differences. At 18 months, the survival free from death and infarction was 93.9%
      for CoCr-EES and 91.3% for PtCr-EES (P=.3), the survival free from
      revascularization was 95.2% vs 94.5% (P=.6) and the survival free from death,
      infarction, and revascularization was 90.6% vs 88%, respectively (P=.4). The
      incidence of definite or probable thrombosis was 1.3% for CoCr-EES and 0.66% for
      PtCr-EES (P=.9). No cases of longitudinal stent compression were observed.
      CONCLUSIONS: The results of this all-comers trial do not show significant
      differences between CoCr-EES and PtCr-EES. However, the sample size is not
      powered to exclude potential differences between stents.

PMID- 23549492
TI  - Vascular healing early after titanium-nitride-oxide-coated stent implantation
      assessed by optical coherence tomography.
AB  - BACKGROUND: The efficacy and safety of titanium-nitride-oxide-coated bioactive
      stents (BASs) were demonstrated in prior studies. In a prospective registry, we
      sought to explore the extent of neointimal coverage of stent struts by optical
      coherence tomography (OCT) at 30 days following the implantation of BASs in an
      unselected non-diabetic population. METHODS: We enrolled 20 consecutive
      nondiabetic patients who underwent BAS implantation. OCT images were obtained at
      30-day follow-up. Binary stent strut coverage was defined as the number of
      covered struts as a percentage of all analyzed struts. RESULTS: Patients
      underwent OCT examination at an average of 30.5 +/- 5.7 days following stent
      implantation. In these, 411 cross-sections were analyzed, including 3780 struts.
      Binary stent strut coverage was 97.2%, and the prevalence of malapposed struts
      was 3.2%. Mean neointimal thickness was 109.7 +/- 83.6 MUm. CONCLUSIONS: In the
      current evaluation by OCT at 30-day follow-up after BAS implantation in an
      unselected non-diabetic cohort, binary stent strut coverage was satisfactory and
      the prevalence of malapposed struts was low.

PMID- 23549493
TI  - Relationship of aortic annular eccentricity and paravalvular regurgitation post
      transcatheter aortic valve implantation with CoreValve.
AB  - BACKGROUND: Significant paravalvular aortic regurgitation (PAR) after
      transcatheter aortic valve implantation (TAVI) is associated with negative
      clinical consequences. We hypothesize that increased eccentricity of the aortic
      annulus is associated with greater PAR. METHODS: Patients with severe aortic
      stenosis underwent multidetector computed tomography (MDCT) before successful
      TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and
      largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus
      were determined. We defined circularity of aortic annulus using the eccentricity
      index (1 - D(min)/D(max)). The primary endpoint was early occurrence of
      significant PAR, defined as > grade II PAR by postprocedural aortography.
      RESULTS: Eighty-four patients, mean age 83 +/- 4 years with a mean aortic valve
      area of 0.7 +/- 0.2 cm2 were included. Twenty patients had postprocedural PAR >
      grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity
      index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively
      determined eccentricity index cut-off of >0.25 was related to significant PAR
      with a sensitivity of 80%, specificity of 86%, and negative predictive value of
      95% (P<.001). On univariate logistic regression, eccentricity index of >0.25
      (P<.001) and device implantation depth (P=.015) correlated with significant PAR,
      while other parameters such as annular calcification and cover index did not. On
      multivariate analysis including only parameters with P<.1 on univariate analysis,
      eccentricity index >0.25 was the sole independent predictor of significant PAR.
      CONCLUSION: Eccentricity index is related to significant PAR after TAVI with
      Medtronic CoreValve. Further larger studies are required to determine the utility
      of this novel index in screening suitable patients for this procedure.

PMID- 23549494
TI  - "Balloon withdrawal technique" to correct prosthesis malposition and treat
      paravalvular aortic regurgitation during TAVI.
AB  - Transcatheter aortic valve implantation (TAVI) is an emerging technology used to
      treat high-risk patients with severe aortic stenosis. During TAVI with the
      CoreValve ReValving System, a balloon is used for the reduction of paravalvular
      regurgitation. However, in this paper, we describe the "balloon withdrawal"
      technique through which the positioning of a second valve can be avoided in case
      of initial malpositioning. The result of the technique was rather encouraging,
      and minimal paravalvular aortic regurgitation was recorded after
      echocardiographic assessment.

PMID- 23549495
TI  - Pain in the neck: a rare complication of transradial cardiac catheterization.
AB  - Vascular and bleeding complications are a known risk of cardiac catheterization.
      In this article, we report a neck hematoma after left-sided transradial cardiac
      catheterization, which is a known but rarely reported complication of this
      procedure.

PMID- 23549496
TI  - Myocardial revascularization in patients with left main coronary disease.
AB  - While coronary artery bypass grafting (CABG) has been the standard of care for
      patients with unprotected left main coronary artery disease, advances in
      percutaneous coronary intervention (PCI) have made stent placement a reasonable
      alternative in selected patients. In this review, we address the results of
      studies comparing PCI with CABG, discuss the invasive evaluation of these
      patients, and the technical approach to percutaneous revascularization.
      Furthermore, we discuss future pivotal trials, which will help define long-term
      outcomes comparing PCI with surgery.

PMID- 23549497
TI  - An overhanging intracoronary stent: an incidental finding or the Sword of
      Damocles?

PMID- 23549498
TI  - Physical exertion at high altitude--another risk factor for coronary stent
      thrombosis?
AB  - We report 2 cases of very late stent thrombosis (VLST) in patients previously
      treated with drug-eluting stent (DES). In both cases, VLST occurred during
      intense physical activities at high altitudes. Exposure to high altitudes alters
      the coagulation cascade, platelet morphology, and function, resulting in a
      hypercoagulable state. In addition, strenuous exercise provokes a procoagulant
      state along with increasing the risk of endothelial damage through the effects on
      coronary blood flow. In light of these cases, we hypothesize that individuals who
      are involved in intense physical activities at high altitudes may be at increased
      risk of stent thrombosis. Use of DES in such patients should be carefully
      considered.

PMID- 23549499
TI  - A concert in the heart: bilateral Melody valve implantation in the branch
      pulmonary arteries.
AB  - Patients undergoing right ventricular outflow tract reconstruction are subject to
      valve and cusp degeneration later in life, requiring further intervention to
      alleviate the pulmonary regurgitation that ensues. In these cases, percutaneous
      pulmonary valve implantation can be an effective alternative to surgery; however,
      since the indications have been limited to dysfunctional valved conduits, only a
      small number of patients have access to this treatment option. We present the
      case of an 18-year-old male with a patch-enlarged right ventricle to pulmonary
      artery conduit who underwent pulmonary valve implantation using two Melody
      transcatheter pulmonary valves (Medtronic, Inc) into the proximal right and left
      branch pulmonary arteries.

PMID- 23549500
TI  - Successful recanalization of a left anterior descending chronic total occlusion
      via an ipsilateral intraseptal collateral using reverse CART technique.
AB  - The retrograde approach using collaterals has been introduced for percutaneous
      dilatation and opening of chronic total occlusion of the coronary arteries. The
      controlled antegrade and retrograde tracking (CART) strategy has been developed
      to improve guidewire crossing and successful recanalization. We herein describe a
      case of left anterior descending chronic total occlusion that was successfully
      recanalized using ipsilateral intraseptal collateral by reverse CART technique.

PMID- 23549501
TI  - Closure of aorto-right ventricular tunnel with Amplatzer duct occluder II.
AB  - Aorto-right ventricular tunnel (ARVT) is a very rare, congenital, abnormal
      extracardiac channel that connects the ascending aorta at or above the
      sinotubular junction to the cavity of the right ventricle. Only 16 cases have
      been reported thus far in the English literature. We report the first
      transcatheter closure of ARVT with the Amplatzer duct occluder II in an infant,
      with both coronary arteries arising from the left coronary sinus and with
      biventricular apical non-compaction.

PMID- 23549502
TI  - Percutaneous transjugular device closure of postoperative residual atrial septal
      defect.
AB  - Percutaneous closure of postoperative malaligned residual atrial septal defect
      was successfully performed from the transjugular approach under transesophageal
      echocardiography guidance in a 38-year-old symptomatic woman with patent femoral
      venous access using the usual hardware. This demonstrates the feasibility of
      transjugular approach as an alternative to femoral or transhepatic approaches in
      patients with difficult atrial septal anatomy who are usually referred for
      surgery.

PMID- 23549503
TI  - Percutaneous coronary intervention and the management of acute coronary syndromes
      in patients with von Willebrand disease.
AB  - BACKGROUND: Von Willebrand disease (vWD) results from quantitative or qualitative
      deficiency of von Willebrand factor (vWF). The occurrence of myocardial
      infarction is very rare in patients with vWD. A few case reports of acute
      coronary syndrome (ACS) in vWD patients are present in the literature, but no
      definite management recommendations are available for such patients. CASE REPORT:
      We report a case of successful percutaneous coronary intervention (PCI) with bare
      metal stent (BMS) implantation in a 46-year-old woman with type 1 vWD and history
      of coronary artery disease (CAD). She received periprocedural dual-antiplatelet
      therapy for 2 weeks and then continued aspirin without any bleeding
      complications. MANAGEMENT PROPOSAL: The optimal management of patients with vWD
      and ACS is complex and presents a therapeutic challenge. We propose that dual
      antiplatelet therapy can be used safely in most vWD patients presenting with ACS
      as most of them are type 1 vWD. PCI with BMS can be done safely. Long-term
      management of these patients requires a systemic approach including hematological
      consultation, ascertaining vWF levels, as well as patient education and close
      outpatient follow-up.

PMID- 23549504
TI  - Self-care behaviour, treatment satisfaction and quality of life in people on
      intensive insulin treatment.
AB  - AIM: The aim of this cross-sectional study was to identify self-care behaviours
      and their relationships with treatment satisfaction and quality of life in people
      attending a structured educational programme for patients on intensive insulin
      therapy. METHODS: A sample of 104 people with diabetes (62 with type-1; 42 with
      type 2) was recruited from the National Institute of Endocrinology and
      Diabetology in Lubochna over six months. The majority of respondents were women
      (62.5%); had multiple daily injections of insulin (73%); diabetic late
      complications (68%) and had not previously participated in the structured
      educational programmes in the specialized diabetes centre (64.4%). Self
      management behaviour data were collected by means of structured interviews with
      patients as well as during clinic visits. For measuring quality of life, the
      Audit Diabetes Dependent Quality of Life questionnaire and for measuring
      satisfaction with their treatment regimen, the Diabetes Treatment Satisfaction
      Questionnaire status version was used. RESULTS: General satisfaction with the
      treatment was significantly higher in people with diabetes, who implemented
      regular self-monitoring of the concentration of glucose in plasma (SMPG). We also
      demonstrated low adherence in the frequency of SMPG. 17% of respondents in our
      study performed daily SMPG. However, 52% respondents reported adaptation of
      insulin dosage in relation to factors such as carbohydrate intake, glycaemia
      values or degree of physical activity. Differences in quality of life due to
      performing the regular self-monitoring of glycaemia, adjustments of insulin doses
      in specific situations as well as carbohydrate counting were not significant.
      CONCLUSION: Performing the regular self-monitoring of glycaemia was associated
      only with higher treatment satisfaction. No significant improvement in quality of
      life was seen in people performing the regular self-monitoring of glycaemia,
      adjustments of insulin doses in specific situations or carbohydrate counting.

PMID- 23549505
TI  - The effect of nano-scale topography on osteogenic differentiation of mesenchymal
      stem cells.
AB  - BACKGROUND: Large bone defects resulting from trauma or disease pose a threat to
      humans. Thus far, tissue engineering as an important clinical approach uses
      cells, growth factors and scaffolds to regenerate large areas of damaged bone
      tissue. Since bone is a nanocomposite structure, it is assumed that nanomaterial
      scaffolds can induce or promote osteogenesis by mimicking the cell niche at nano
      level. METHODS AND RESULTS: In this review we highlighted the effect of nano
      scale topography on osteogenic differentiation of Mesenchymal Stem Cells (MSCs)
      as potent cell candidates in bone engineered constructs. The key point in the
      induction of differentiation by nanomaterials is the discontinuity in their
      topography. This leads to alteration in protein adsorption and restriction of
      extracellular matrix deposition by the cells and consequently leads to changes in
      cell morphology and the frequency of accessible sites for cell adhesion. Here, we
      have reviewed the literature on the role of different types of nanomateial
      scaffolds in osteogenic differentiation of these cells. Since little is known
      about the underlying molecular networks induced by nanomaterials, we also
      reviewed possible underlying mechanisms of nanotopographical effects on the
      osteogenic differentiation of MSCs. CONCLUSIONS: Nano-scale materials provide a
      niche which is very similar to native bone in geometry and stiffness. Such nano
      scale topographies improve the function of MSC-based engineered constructs in
      regeneration of bone defects.

PMID- 23549506
TI  - X-linked agammaglobulinemia caused by new mutation in BTK gene: a case report.
AB  - AIM: Primary immunodeficiencies (PID) are becoming a recognized public health
      problem worldwide. The most important subgroup of these disorders are the
      antibody deficiencies. X-linked agammaglobulinaemia was the first described
      entity of this group and is characterised by early onset of recurrent bacterial
      infections, profound deficiency of all immunoglobulin isotypes and markedly
      reduced number of peripheral B-lymphocytes. CASE REPORT: We report the case of a
      10-year old boy with X-linked agammaglobulinaemia caused by a previously non
      described mutation in BTK gene with typical clinical presentation but delayed
      diagnosis. Following diagnosis, substitution therapy with intravenous
      immunoglobulins was started and the clinical status of the patient improved.
      CONCLUSION: We reported a case of X-linked agammaglobulinaemia with delayed
      diagnosis despite the typical anamnestic signs for primary humoral
      immunodeficiency. The disease was caused by a previously non-reported mutation in
      the BTK gene. Measurement of serum immunoglobulins should be performed in all
      children with recurrent, complicated respiratory infections as a screening test
      for humoral immunodeficiencies.

PMID- 23549507
TI  - 13C-methacetin breath test in the evaluation of disease severity in patients with
      liver cirrhosis.
AB  - AIMS: The non-invasive (13)C-methacetin ((13)C-MBT) breath test has been proposed
      as a measure of metabolic liver function that improves the diagnostic efficacy of
      serologic and biochemical tests in assessing hepatic functional capacity and
      liver disease severity, The goal of this study was to establish the clinical
      utility of this test in quantifying hepatic metabolic function in patients with
      liver cirrhosis of varying severity and to compare (13)C-MBT measurements with
      the AST/ALT ratio, APRI score, and other routine liver tests. METHODS: Routine
      liver function tests including serum bilirubin, aspartate aminotransferase
      activity (AST), alanine aminotransferase (ALT), AST/ALT ratio, the APRI score,
      the percentage of dose rate (PDR) and cumulative percentage of dose rate (CPDR)
      of the (13)C-MBT were evaluated in 52 cirrhotic patients of alcohol etiology
      (Child-Pugh A/B/C 10/28/14) and 37 healthy controls. RESULTS: The (13)C-MBT
      differed significantly between healthy controls and cirrhotic patients at all
      time intervals measured. It also proved the ability to differentiate patients
      with liver cirrhosis based on severity of hepatic impairment corresponding to the
      Child-Pugh classification A vs. B vs. C. The ROC curve analysis suggested that
      the best prediction is provided by time intervals between the 10th - 20th or 10th
      - 40th minute of PDR. CONCLUSIONS: The (13)C-MBT offers a reliable means for
      quantification of hepatic metabolic function over the complete range of
      functional liver impairment. It is non-invasive, easy to perform and completely
      safe.

PMID- 23549508
TI  - Optical coherence tomography in progressive cone dystrophy.
AB  - AIM: The aim of the study was to analyse different clinical pictures in patients
      with progressive cone dystrophy (PCD), to compare these with the results of
      optical coherence tomography (OCT) and to evaluate the benefits of this method
      for diagnosis. METHODS: The group consisted of 16 patients (32 eyes) with PCD.
      All patients were examined for visual acuity, colour sense and visual field. We
      performed biomicroscopic examination, photo-documentation, fluorescein
      angiography, electrophysiological tests and OCT. RESULTS: Using biomicroscopy and
      fluorescein angiography, we found changes in the retinal pigment epithelium
      ranging from barely detectable changes up to the typical bull's eye appearance.
      In all the eyes, OCT established statistically significant reduction in the
      thickness and structural changes in the neuroretina of the macula. Atrophy was
      evident especially in the outer nuclear layer, in the photoreceptor inner
      segment/outer segment junction and in the retinal pigment epithelium. Visual
      acuity was mainly dependent on the degree to which the continuity of the
      photoreceptor inner segment/outer segment junction layer was maintained. Eyes
      with better preserved neuroretinal structure in the fovea centralis had generally
      less reduced thickness of the retina and a better visual acuity. CONCLUSION: OCT
      specifies the quantitative and qualitative changes in the macula and may
      contribute significantly to the diagnosis of the progressive cone dystrophy,
      particularly in the early stages of the disease which is difficult to diagnose.

PMID- 23549509
TI  - Current treatment methods for long occlusions of the femoropopliteal segment in
      patients with intermittent claudication: Minireview.
AB  - Backround. Intermittent claudication is a classic symptom of peripheral arterial
      disease. It is mainly treated conservatively but if this fails, a form of
      revascularization is indicated. The revascularization in chronic occlusion of
      femoropopliteal region is currently performed by two basic methods: the standard
      method of surgical bypass and the newer miniinvasive alternative represented by
      the endovascular method. The treatment of patients with solely claudication and
      long occlusion of femoropopliteal region remains controversial. The aim of this
      minireview was to determine whether surgical bypass is still the best method of
      choice in a time of endovascular techniques. METHODS: A MEDLINE search for
      original and review articles using key terms, intermittent claudication and long
      femoropopliteal oclusion. RESULTS AND CONCLUSION: No ideal treatment for long
      occlusions of the femoropopliteal segment has been established to date. It is
      clear that the role of endovascular techniques in the treatment of SFA occlusions
      is increasing. It remains that, lower risk patients with claudication should be
      examined to assess the quality of veins suitable for revascularization and bypass
      should be selected as the first method of choice.

PMID- 23549510
TI  - An unusual reason for severe bradycardia leading to cardiac arrest during general
      anaesthesia: a case report.
AB  - BACKGROUND: Takotsubo cardiomyopathy also known as transient balooning syndrome
      is an increasingly reported phenomenon characterized by acute reversible apical
      or midventricular dysfunction. This stress- induced cardiomyopathy mimics
      myocardial infarction, but without significant coronary artery disease, and
      rarely presents in perioperative period. METHODS AND RESULTS: We report a case of
      postmenopausal woman scheduled to undergo elective cholecystectomy, with no
      history of coronary artery disease. She presented perioperatively with Takotsubo
      cardiomyopathy by unique manifestation-asystoly. This uncommon cause of cardiac
      arrest during anaesthesia was possibly induced by preoperative emotional stress.
      There was full recovery thanks to intensive management. In Takotsubo
      cardiomyopathy related cardiogenic shock we used the calcium sensitiser
      levosimendan successfully. CONCLUSION: Takotsubo cardiomyopathy has an excellent
      long-term prognosis and nearly all patients have full recovery of left
      ventricular function. We emphasize the importance of heavy premedication by
      stress compromised patients and the need of sufficiently deep anaesthesia and
      analgesia during surgeries.

PMID- 23549511
TI  - Organs of BALB/c mice can be injured in course of tularemia.
AB  - BACKGROUND: Francisella tularensis is a biological agent exploitable for
      bioterrorism and biological warfare purposes due to serious pathogenic
      progression and easy dissemination. Despite intensive research in the past, some
      adverse consequences remain unclear. One consequence of this pathogen is
      oxidative stress. AIMS: The aim of this study was to undertake ex vivo assays for
      monitoring the disease in mice and increase our knowledge of the oxidative stress
      induced by tularemia. METHODS: The mouse BALB/c model was chosen and the animals
      were infected by a dose 10(4) CFU of F. tularensis. After five days, the animals
      were euthanized. Blood immediately processed in plasma, spleen and liver were
      sampled from the cadavers. Oxidative stress markers, cytokines and
      histopathological were undertaken. RESULTS: There was a significant link between
      oxidative stress and tularemia. Particularly elevated levels of malondialdehyde
      and decreased levels of low molecular weight antioxidants were found in the liver
      and spleen of tularemia-infected animals. The histopathological findings
      correlated well with the oxidative stress markers. The liver and spleen were
      proven to be significantly at risk from the disease and an association between
      stress and neutrophils in the affected organs was found. The histopathology
      excluded risk to other organs such as the kidney and or heart. CONCLUSIONS:
      Oxidative stress plays a significant role in tularemia infection in mice and this
      was confirmed by the histology.

PMID- 23549512
TI  - Variability of post-exercise pulmonary capillary wedge pressure recovery.
      Implications for noninvasive echocardiographic diagnostics.
AB  - AIM: The aim of our study was to assess the course of immediate post-exercise
      pulmonary capillary wedge pressure (PCWP) changes to identify the optimal time
      window for the noninvasive diagnostics of exercise-induced PCWP elevation.
      METHODS AND RESULTS: Seventy-one patients at risk of heart failure with normal
      left ventricular ejection fraction underwent simultaneous exercise
      echocardiography and right heart catheterization. The ratio of early left
      ventricular filling velocity (E) to early diastolic mitral annular velocity (e')
      was used to predict noninvasively exercise-induced PCWP elevation. Fifty-one
      patients had exercise-induced PCWP elevation >= 8 mmHg and reached peak exercise
      PCWP >= 20 mmHg. Rapid post-exercise recovery of PCWP within 2 min was achieved
      in 18 (35.3%) patients. Intermediate post-exercise PCWP recovery at 3 and 4 min
      was found in 16 (31.4%) patients while late post-exercise PCWP recovery (>= 5
      min) was achieved in 17 (33.3%) patients. CONCLUSION: The course of post-exercise
      PCWP recovery is highly variable, and a significant proportion of patients have
      only a brief period (<= 2 min) of exercise-induced PCWP elevation. This fact
      should be taken into account in noninvasive assessment of exercise-induced PCWP.

PMID- 23549513
TI  - Therapeutic monitoring of psychoactive drugs - antidepressants: a review.
AB  - BACKGROUND: Major depression, is one of the most prevalent mental disorders in
      Europe and the USA. The dramatic rise in pharmacological antidepressants is
      mainly due to increase in use of selective serotonin reuptake inhibitors,
      serotonin and norepinephrine reuptake inhibitors and other new generation
      antidepressants. In clinical practice, optimum individual doses are often guided
      by trial-and-error. This article reviews the available literature on therapeutic
      monitoring of antidepressant drugs. METHODS: A search using MEDLINE (english
      language reports, 1983 - August 2012) with the key words for antidepressant drugs
      and therapeutic drug monitoring. RESULTS: There is a need for monitoring
      antidepressants due to wide interindividual pharmacokinetic variability. At the
      same drug dose, a more than 20-fold variation in steady state concentration of
      drug in the body may result: people differ in their ability to absorb,
      distribute, metabolise and excrete drugs for reasons of concurrent disease, age,
      gender, smoking and eating habits, concomitant medication and genetics.
      CONCLUSIONS: Monitoring of antidepressant drugs enables us to individualise drug
      doses based on rational therapy, minimalise side effects, reduce morbidity and
      mortality and cut the cost of health care. Phenotyping and genotyping could
      increase therapeutic drug monitoring furthere.

PMID- 23549514
TI  - Long term visual outcome after arteriolar constriction in patients with branch
      retinal vein occlusion.
AB  - AIM: To evaluate the final best corrected visual acuity (BCVA) in patients with
      branch retinal vein occlusion (BRVO) treated with either (1) laser arteriolar
      constriction (ACo) or (2) the standard treatment recommended by the Branch Vein
      Occlusion Study Group (grid laser photocoagulation (GLP) or only observation (if
      indication criteria for GLP were not met). METHODS: 358 BRVOs were treated in
      three different ways: early ACo (n=133) performed <=9 weeks after onset of BRVO,
      late ACo (n=62) performed >9 weeks after onset and controls which included GLP
      and observation (n=163). The groups were further divided according to initial
      BCVA into: <=0.1; 0.16-0.3 and >=0.4. RESULTS: Based on the proportion of 1 year
      BCVA<=0.1 as a risk category, the results of early ACo (3.8%) were significantly
      better than for the controls (22.7%, P<0.001) and late ACo (16.1%, P=0.006). The
      greatest difference in final BCVA was in patients with the worst initial VA
      (<=0.1). In the intermediate initial BCVA group 0.16-0.3, a significant
      difference was only found between the early ACo group and controls (P=0.007).
      There was no significant difference between any treatment group and prevalence of
      a final BCVA<=0.1 for patients with an initial BCVA>=0.4. CONCLUSIONS: Early ACo
      significantly reduces the prevalence of a final BCVA<=0.1 in patients with BRVO
      and an initial BCVA<=0.3 compared to controls (standard treatment treated with
      GLP or observed).

PMID- 23549515
TI  - Impact of retransfusion of blood processed in cell-saver on coagulation versus
      cardiopulmonary bypass: a prospective observational study using
      thromboelastography.
AB  - AIMS: To compare an impact of retransfusion of blood processed in cell-saver (CS)
      with that of cardiopulmonary bypass (CPB) on blood coagulation in patients
      undergoing cardiac surgery. METHODS: Prospective observational study using
      thromboelastography (TEG). RESULTS: TEG samples from 170 patients were analyzed.
      Cardiopulmonary bypass was used in 100 patients while 70 patients were operated
      off-pump. In 20 off-pump patients collected blood was processed by cell-saver and
      returned. In all patients clot formation after heparin neutralization by
      protamine was unimpaired. However, there was a significant increase in
      fibrinolysis defined by the TEG parameter Lysis time 30 min after the maximum
      amplitude of the clot was reached (Ly30) in groups with CPB or CS but this
      increase still did not exceed the threshold for clinical fibrinolysis (Ly30 >
      7.5%). In the group without CPB there was no significant impact on coagulation.
      CONCLUSION: Surgery that avoids CPB and/or CS is the gentlest method for inducing
      blood coagulation.

PMID- 23549516
TI  - Treatment of central serous chorioretinopathy with beta-blocker metipranolol.
AB  - AIM: The purpose of this study was to evaluate the effect of the systemically
      administered betablocker metipranolol on the course of central serous
      chorioretinopathy (CSC). METHODS: A prospective double-blind study involving 48
      patients with a first attack of CSC not exceeding two weeks and who agreed to the
      follow-up ophthalmology examinations every week. The group was divided into a
      metipranolol group (n=23), receiving 10 mg of drug twice per day and a placebo
      group (n=25). The outcome measure was time in weeks from drug intervention
      (metipranolol vs. placebo) to reattachment of macula neuroepithelium. RESULTS:
      There was no statistically significant difference in duration of CSC in patients
      who used metipranolol and those who used placebo (P=0.341). CONCLUSIONS: In a
      prospective double-blind study, we found no effect of the betablocker
      metipranolol on the duration of central serous chorioretinopathy.

PMID- 23549517
TI  - The complex interplay between inflammation, the microbiota and colorectal cancer.
AB  - The microbiome has captured the attention of scientists from multiple research
      fields including ecology, immunology, microbiology and cancer biology. The
      microbial community living in the gastrointestinal tract is the most abundant and
      diverse niche of the human body and it is not surprising that microbiome research
      has predominantly focused upon this organ system. In this addendum, we summarize
      the latest developments in microbiome research on inflammatory bowel diseases and
      colorectal cancer. In addition, we highlight our recent findings that chronic
      intestinal inflammation modulates microbial community composition and the
      development of colorectal cancer. Our findings redefine the paradigm of
      inflammation-associated cancer by illuminating the key role of bacteria in
      development of colorectal cancer.

PMID- 23549518
TI  - Improved patient survival with simultaneous pancreas and kidney transplantation
      in recipients with diabetic end-stage renal disease.
AB  - AIMS/HYPOTHESIS: We aimed to determine whether simultaneous pancreas and kidney
      (SPK) transplantation would improve patient and kidney graft survival in diabetic
      end-stage renal disease (ESRD) compared with kidney transplantation alone (KTA).
      METHODS: Follow-up data were retrieved for all 630 patients with diabetic ESRD
      who had received SPK or KTA at our centre from 1983 to the end of 2010.
      Recipients younger than 55 years of age received either an SPK (n = 222) or, if
      available, a single live donor kidney (LDK; n = 171). Older recipients and
      recipients with greater comorbidity received a single deceased donor kidney (DDK;
      n = 237). Survival was analysed by the Kaplan-Meier method and in multivariate
      Cox regression analysis adjusting for recipient and donor characteristics.
      RESULTS: Patient survival was superior in SPK compared with both LDK and DDK
      recipients in univariate analysis. Follow-up time (mean +/- SD) after
      transplantation was 7.1 +/- 5.7 years. Median actuarial patient survival was 14.0
      years for SPK, 11.5 years for LDK and 6.7 years for DDK recipients. In
      multivariate analyses including recipient age, sex, treatment modality, time on
      dialysis and era, SPK transplantation was protective for all-cause mortality
      compared with both LDK (p = 0.02) and DDK (p = 0.029) transplantation. After the
      year 2000, overall patient survival improved compared with previous years (HR
      0.40, 95% CI 0.30, 0.55; p < 0.001). Pancreas graft survival also improved after
      2000, with a 5 year graft survival rate of 78% vs 61% in previous years (1988
      1999). CONCLUSIONS/INTERPRETATION: Recipients of SPK transplants have superior
      patient survival compared with both LDK and DDK recipients, with improved results
      seen over the last decade.

PMID- 23549519
TI  - Structured personal care of type 2 diabetes: a 19 year follow-up of the study
      Diabetes Care in General Practice (DCGP).
AB  - AIMS/HYPOTHESIS: This study is a 19 year observational follow-up of a pragmatic
      open multicentre cluster-randomised controlled trial of 6 years of structured
      personal diabetes care starting from diagnosis. METHODS: A total of 1,381
      patients aged >= 40 years and newly diagnosed with type 2 diabetes were followed
      up in national registries for 19 years. Clinical follow-up was at 6 and 14 years
      after diabetes diagnosis. The original 6 year intervention included regular
      follow-up and individualised goal setting, supported by prompting of doctors,
      clinical guidelines, feedback and continuing medical education
      (ClinicalTrials.gov NCT01074762). The registry-based endpoints were: incidence of
      any diabetes-related endpoint; diabetes-related death; all-cause mortality;
      myocardial infarction (MI); stroke; peripheral vascular disease; and
      microvascular disease. RESULTS: At 14 year clinical follow-up, group differences
      in risk factors from the 6 year follow-up had levelled out, although the
      prevalence of (micro)albuminuria and level of triacylglycerols were lower in the
      intervention group. During 19 years of registry-based monitoring, all-cause
      mortality was not different between the intervention and comparison groups (58.9
      vs 62.3 events per 1,000 patient-years, respectively; for structured personal
      care, HR 0.94, 95% CI 0.83, 1.08, p = 0.40), but a lower risk emerged for fatal
      and non-fatal MI (27.3 vs 33.5, HR 0.81, 95% CI 0.68, 0.98, p = 0.030) and any
      diabetes-related endpoint (69.5 vs 82.1, HR 0.83, 95% CI 0.72, 0.97, p = 0.016).
      These differences persisted after extensive multivariable adjustment.
      CONCLUSIONS/INTERPRETATION: In concert with features such as prompting, feedback,
      clinical guidelines and continuing medical education, individualisation of goal
      setting and drug treatment may safely be applied to treat patients newly
      diagnosed with type 2 diabetes to lower the risk of diabetes complications.

PMID- 23549520
TI  - Efficacy of early physical therapy in severe Bell's palsy: a randomized
      controlled trial.
AB  - BACKGROUND: Bell's palsy (BP) is the most frequent form of peripheral palsy of
      the facial nerve. Prognosis for recovery is good for most patients; in the
      remaining cases, different grades of residual impairment persist. Physical
      therapy, in association with drug administration, aims to improve outcomes.
      OBJECTIVE: To assess the efficacy of early physical therapy in association with
      standard drug administration versus pharmacological therapy only, in terms of
      time to maximum gains and grade of recovery of function, and to examine who will
      most benefit from rehabilitation. METHODS: From June 2008 to May 2010, 232
      individuals were evaluated. The 87 patients meeting the eligibility criteria were
      randomly assigned to the experimental group (prednisone and valacyclovir plus
      physical therapy, n = 39) or the control group (pharmacological therapy, n = 48)
      within 10 days of onset. Intention-to-treat analyses were done. RESULTS: The
      physical therapy had a significant effect on grade (P = .038) and time (P = .044)
      to recovery only in patients presenting with severe facial palsy (House-Brackmann
      [HB] grade V/VI). No significant differences were found between the study and
      control groups for outcome of synkinesis. CONCLUSION: Physical therapy appears to
      be effective only in the more severe BP (baseline HB grade V/VI), whereas less
      severe BP (baseline HB grade IV) results in complete spontaneous recovery,
      regardless of physical therapy.

PMID- 23549522
TI  - Catechol-O-methyltransferase polymorphism influences outcome after ischemic
      stroke: a prospective double-blind study.
AB  - BACKGROUND: To explore whether a polymorphism in dopamine metabolism influences
      the effectiveness of neurological rehabilitation and the outcome after ischemic
      stroke. METHODS: The Barthel Index (BI) and the Rivermead Motor Assessment (RMA)
      were assessed in 78 moderately affected stroke patients (1) after they had
      entered a neurological inpatient rehabilitation, (2) after 4 weeks of
      rehabilitation therapy, and (3) 6 months later. Polymorphisms of the gene
      encoding catechol-O-methyltransferase (COMT) were determined. BI and RMA results
      were analyzed with respect to the genetic profiles of COMT. RESULTS: Carriers of
      COMT Val/Val alleles showed better results in BI and RMA than COMT Met/Met
      carriers at all 3 time points. Val/Met carriers exhibited results in between the
      homozygotes, suggesting a gene-dose relationship. Altogether, BI and RMA results
      were highly correlated. CONCLUSION: Stroke patients with COMT Val/Val alleles had
      higher motor functions and abilities of activities of daily living even at the
      beginning of the rehabilitation period. All patient groups improved during the
      rehabilitation period to a similar degree, suggesting that physical therapy is
      comparably effective in all polymorphism subtypes.

PMID- 23549521
TI  - Transfer of training between distinct motor tasks after stroke: implications for
      task-specific approaches to upper-extremity neurorehabilitation.
AB  - BACKGROUND: Although task-specific training is emerging as a viable approach for
      recovering motor function after stroke, there is little evidence for whether the
      effects of such training transfer to other functional motor tasks not directly
      practiced in therapy. OBJECTIVE: The purpose of the current study was to test
      whether training on one motor task in individuals with chronic hemiparesis
      poststroke would transfer to untrained tasks that were either spatiotemporally
      similar or different. METHODS: In all, 11 participants with chronic mild to
      moderate hemiparesis following stroke completed 5 days of supervised massed
      practice of a feeding task with their affected side. Performance on the feeding
      task, along with 2 other untrained functional upper-extremity motor tasks
      (sorting, dressing) was assessed before and after training. RESULTS: Performance
      of all 3 tasks improved significantly after training exclusively on 1 motor task.
      The amount of improvement in the untrained tasks was comparable and was not
      dependent on the degree of similarity to the trained task. CONCLUSIONS: Because
      the number and type of tasks that can be practiced are often limited within
      standard stroke rehabilitation, results from this study will be useful for
      designing task-specific training plans to maximize therapy benefits.

PMID- 23549523
TI  - Changes in sleep patterns following traumatic brain injury: a controlled study.
AB  - BACKGROUND: Sleep changes are frequently reported following traumatic brain
      injury (TBI) and have an impact on rehabilitation and quality of life following
      injury. Potential causes include injury to brain regions associated with sleep
      regulation, as well as secondary factors, including depression, anxiety, and
      pain. Understanding the nature and causes of sleep changes following TBI
      represents a vital step in developing effective treatments. OBJECTIVE: The study
      aimed to investigate subjective sleep changes in a community-based sample of
      individuals with TBI in comparison with noninjured age- and sex-matched controls
      and to explore the impact of secondary factors (pain, anxiety, depression,
      employment) on these self-reported sleep changes. METHODS: A total of 153
      participants with mild to severe TBI and 128 noninjured controls completed self
      report measures relating to their sleep quality, daytime sleepiness, mood,
      fatigue, and pain and completed a sleep diary each day for 7 days. RESULTS:
      Compared with the noninjured controls, participants with TBI reported
      significantly poorer sleep quality and higher levels of daytime sleepiness; sleep
      diaries revealed longer sleep onset latency, poorer sleep efficiency, longer
      sleep duration, and more frequent daytime napping in the TBI group, as well as
      earlier bedtimes and greater total sleep duration. Anxiety, depression, and pain
      were associated with poorer sleep quality. Greater injury severity was also
      associated with a need for longer sleep time. CONCLUSION: These findings
      highlight the importance of assessing and addressing pain, anxiety, and
      depression as part of the process of treating TBI-related sleep disturbances.

PMID- 23549525
TI  - The use of siloxanes, silsesquioxanes, and silicones in organic semiconducting
      materials.
AB  - Optimization of the physical and electronic properties of organic semiconductors
      is a key step in improving the performance of organic light emitting diodes,
      organic photovoltaics, organic field effect transistors, and other electronic
      devices. Separate tuning of the physical and electronic properties of these
      organic semiconductors can be achieved by the hybridization of organo-silicon
      structures (silicones, siloxanes, silsesquioxanes) with organic semiconductors.
      Common chemical means to achieve this hybridization are summarized while a large
      range of literature examples are covered to demonstrate the range and flexibility
      of this synthetic strategy.

PMID- 23549524
TI  - Clustering of antimicrobial resistance outbreaks across bacterial species in the
      intensive care unit.
AB  - BACKGROUND: There are frequent reports of intensive care unit (ICU) outbreaks due
      to transmission of particular antibiotic-resistant bacteria. Less is known about
      the burden of outbreaks of resistance due to horizontal transfer of mobile
      genetic elements between species. Moreover, the potential of existing statistical
      software as a preliminary means for detecting such events has never been
      assessed. This study uses a software package to determine the burden of species
      and resistance outbreaks in 2 adjacent ICUs and to look for evidence of
      clustering of resistance outbreaks consistent with interspecies transmission of
      resistance elements. METHODS: A retrospective analysis of data from 2 adjacent 15
      bed adult ICUs between 2002 and 2009 was undertaken. Detection of bacterial
      species-groups and resistance outbreaks was conducted using SaTScan and WHONet
      SaTScan software. Resampling and permutation methods were applied to investigate
      temporal clustering of outbreaks. RESULTS: Outbreaks occurred for 69% of
      bacterial species-groups (18/26), and resistance outbreaks were detected against
      63% of antibiotics (10/16). Resistance outbreaks against 7 of 10 antibiotics were
      observed in multiple species-groups simultaneously and there was evidence of
      inter-species-group dependence for 4 of 7 antibiotics; background temporal
      changes in resistance did not explain the temporal aggregation of outbreaks in 3
      of 7 antibiotics. CONCLUSIONS: Species outbreaks occurred for the majority of
      bacteria commonly identified in the ICU. There was evidence for frequent temporal
      clustering of resistance outbreaks consistent with interspecies transmission of
      resistance elements. Wider application of outbreak detection software combined
      with targeted sequencing of bacterial genomes is needed to understand the
      contribution of interspecies gene transfer to resistance emergence.

PMID- 23549526
TI  - Ultra-wideband tunable resonator based on varactor-loaded complementary split
      ring resonators on a substrate-integrated waveguide for microwave sensor
      applications.
AB  - This paper presents the modeling, design, fabrication, and measurement of an
      ultra-wideband tunable twoport resonator in which the substrate-integrated
      waveguide, complementary split-ring resonators (CSRRs), and varactors are
      embedded on the same planar platform. The tuning of the passband frequency is
      generated by a simple single dc voltage of 0 to 36 V, which is applied to each
      varactor on the CSRRs. Different capacitance values and resonant frequencies are
      produced while a nearly constant absolute bandwidth is maintained. The resonant
      frequency is varied between 0.83 and 1.58 GHz and has a wide tuning ratio of 90%.

PMID- 23549527
TI  - Microbubble cavitation imaging.
AB  - Ultrasound cavitation of microbubble contrast agents has a potential for
      therapeutic applications such as sonothrombolysis (STL) in acute ischemic stroke.
      For safety, efficacy, and reproducibility of treatment, it is critical to
      evaluate the cavitation state (moderate oscillations, stable cavitation, and
      inertial cavitation) and activity level in and around a treatment area. Acoustic
      passive cavitation detectors (PCDs) have been used to this end but do not provide
      spatial information. This paper presents a prototype of a 2-D cavitation imager
      capable of producing images of the dominant cavitation state and activity level
      in a region of interest. Similar to PCDs, the cavitation imaging described here
      is based on the spectral analysis of the acoustic signal radiated by the
      cavitating microbubbles: ultraharmonics of the excitation frequency indicate
      stable cavitation, whereas elevated noise bands indicate inertial cavitation; the
      absence of both indicates moderate oscillations. The prototype system is a
      modified commercially available ultrasound scanner with a sector imaging probe.
      The lateral resolution of the system is 1.5 mm at a focal depth of 3 cm, and the
      axial resolution is 3 cm for a therapy pulse length of 20 MUs. The maximum frame
      rate of the prototype is 2 Hz. The system has been used for assessing and mapping
      the relative importance of the different cavitation states of a microbubble
      contrast agent. In vitro (tissue-mimicking flow phantom) and in vivo (heart,
      liver, and brain of two swine) results for cavitation states and their changes as
      a function of acoustic amplitude are presented.

PMID- 23549528
TI  - Improved elevational and azimuthal motion tracking using sector scans.
AB  - Ultrasound data motion tracking is widely used to estimate relative
      tissue/transducer motion, for example in freehand 3-D imaging, in which
      successive 2-D ultrasound scan planes are registered in a 3-D volume. Speckle
      tracking and decorrelation-based methods are used to estimate motion in the
      azimuthal and elevational planes. However, the performance of speckle-tracking is
      significantly degraded in sectorscan systems because of point-spread function
      rotation with lateral motion. In this paper, we develop a new method for joint
      azimuthal?elevational motion estimation based on the complex correlation of
      individual IQ-demodulated sector-scan A-lines arising from tissue motion in 3-D
      space. We show that our method has performance benefits over both speckle
      tracking and decorrelation-based tracking for motion estimation in sector-scan
      systems, particularly when there is both elevational and azimuthal motion. Motion
      tracking efficacy is further demonstrated by improved freehand imaging of a known
      target (anatomically accurate 3-D-printed lumbar spine model) in a tissue
      mimicking phantom, with an rms surface distance error of 1.2 mm, compared with
      2.43 mm for conventional methods. These data indicate that the new algorithm is
      capable of improved tracking performance for sector scan systems, enabling
      effective freehand 3-D scanning.

PMID- 23549530
TI  - Cranial nerve threshold for thermal injury induced by MRI-guided high-intensity
      focused ultrasound (MRgHIFU): preliminary results on an optic nerve model.
AB  - Future clinical applications of magnetic resonance imaging-guided high-intensity
      focused ultrasound (MRgHIFU) are moving toward the management of different
      intracranial pathologies. We sought to validate the production, safety, and
      efficacy of thermal injury to cranial nerves generated by MRgHIFU. In this study,
      five female domestic pigs underwent a standard bifrontal craniectomy under
      general anesthesia. Treatment was then given using an MRgHIFU system to induce
      hyperthermic ablative sonication (6 to 10 s; 50 to 2000 J.) Histological analyses
      were done to confirm nerve damage; temperature measured on the optic nerve was
      approximately 53.4 degrees C (range: 39 degrees C to 70 degrees C.) Histology
      demonstrated a clear definition between a necrotic, transitional zone, and normal
      tissue. MRgHIFU induces targeted thermal injury to nervous tissue within a
      specific threshold of 50 degrees C to 60 degrees C with the tissue near the
      sonication center yielding the greatest effect; adjacent tissue showed minimal
      changes. Additional studies utilizing this technology are required to further
      establish accurate threshold parameters for optic nerve thermo-ablation.

PMID- 23549531
TI  - Strain estimation in elastography using scale-invariant keypoints tracking.
AB  - This paper proposes a novel strain estimator using scale-invariant keypoints
      tracking (SIKT) for ultrasonic elastography. This method is based on tracking
      stable features between the pre- and post-compression A-lines to obtain tissue
      displacement estimates. The proposed features, termed scaleinvariant keypoints,
      are independent of signal scale change according to the scale-space theory, and
      therefore can preserve their patterns while undergoing a substantial range of
      compression. The keypoints can be produced by searching for repeatedly assigned
      points across all possible scales constructed from the convolution with a one
      parameter family of Gaussian kernels. Because of the distinctive property of the
      keypoints, the SIKT method could provide a reliable tracking over changing
      strains, an effective resistance to anamorphic noise and sonographic noise, and a
      significant reduction in processing time. Simulation and experimental results
      show that the SIKT method is able to provide better sensitivity, a larger dynamic
      range of the strain filter, higher resolution, and a better contrast- to-noise
      ratio (CNRe) than the conventional methods. Moreover, the computation time of the
      SIKT method is approximately 5 times that of the cross-correlation techniques.

PMID- 23549529
TI  - Acoustic radiation force elasticity imaging in diagnostic ultrasound.
AB  - The development of ultrasound-based elasticity imaging methods has been the focus
      of intense research activity since the mid-1990s. In characterizing the
      mechanical properties of soft tissues, these techniques image an entirely new
      subset of tissue properties that cannot be derived with conventional ultrasound
      techniques. Clinically, tissue elasticity is known to be associated with
      pathological condition and with the ability to image these features in vivo;
      elasticity imaging methods may prove to be invaluable tools for the diagnosis
      and/or monitoring of disease. This review focuses on ultrasound-based elasticity
      imaging methods that generate an acoustic radiation force to induce tissue
      displacements. These methods can be performed noninvasively during routine exams
      to provide either qualitative or quantitative metrics of tissue elasticity. A
      brief overview of soft tissue mechanics relevant to elasticity imaging is
      provided, including a derivation of acoustic radiation force, and an overview of
      the various acoustic radiation force elasticity imaging methods.

PMID- 23549532
TI  - Ultrasound bio-microscopic image segmentation for evaluation of zebrafish cardiac
      function.
AB  - Zebrafish can fully regenerate their myocardium after ventricular resection
      without evidence of scars. This extraordinary regenerative ability provides an
      excellent model system to study the activation of the regenerative potential for
      human heart tissue. In addition to the morphology, it is vital to understand the
      cardiac function of zebrafish. To characterize adult zebrafish cardiac function,
      an ultrasound biomicroscope (UBM) was customized for real-time imaging of the
      zebrafish heart (about 1 mm in diameter) at a resolution of around 37 MUm.
      Moreover, we developed an image segmentation algorithm to track the cardiac
      boundary and measure the dynamic size of the zebrafish heart for further
      quantification of zebrafish cardiac function. The effectiveness and accuracy of
      the proposed segmentation algorithm were verified on a tissuemimicking phantom
      and in vivo zebrafish echocardiography. The quantitative evaluation demonstrated
      that the accuracy of the proposed algorithm is comparable to the manual
      delineation by experts.

PMID- 23549533
TI  - Simultaneous quantification of flow and tissue velocities based on multi-angle
      plane wave imaging.
AB  - A quantitative angle-independent 2-D modality for flow and tissue imaging based
      on multi-angle plane wave acquisition was evaluated. Simulations of realistic
      flow in a carotid artery bifurcation were used to assess the accuracy of the
      vector Doppler (VD) technique. Reduction in root mean square deviation from 27
      cm/s to 6 cm/s and 7 cm/s to 2 cm/s was found for the lateral (vx) and axial (vz)
      velocity components, respectively, when the ensemble size was increased from 8 to
      50. Simulations of a Couette flow phantom (vmax = 2.7 cm/s) gave promising
      results for imaging of slowly moving tissue, with root mean square deviation of
      4.4 mm/s and 1.6 mm/s for the x- and z-components, respectively. A packet
      acquisition scheme providing both B-mode and vector Doppler RF data was
      implemented on a research scanner, and beamforming and further post-processing
      was done offline. In vivo results of healthy volunteers were in accordance with
      simulations and gave promising results for flow and tissue vector velocity
      imaging. The technique was also tested in patients with carotid artery disease.
      Using the high ensemble vector Doppler technique, blood flow through stenoses and
      secondary flow patterns were better visualized than in ordinary color Doppler.
      Additionally, the full velocity spectrum could be obtained retrospectively for
      arbitrary points in the image.

PMID- 23549534
TI  - New method for real-time dynamic focusing through interfaces.
AB  - In nondestructive evaluation (NDE) a coupling medium (wedge) is frequently
      inserted between the array probe and the object being evaluated. In this
      situation, focal law computing is complicated by the refraction effects at the
      interface. Furthermore, there are not known techniques to perform dynamic
      focusing by hardware in these conditions. This work addresses these problems by
      following a two-step procedure. First, a virtual array that operates in a single
      medium with nearly equivalent time-of-flight to the foci is obtained. Then,
      simple hardware is proposed to perform dynamic focusing in real-time. It operates
      with arrays of any geometry as required by the virtual array in presence of
      arbitrarily shaped interfaces. The paper describes the theory and evaluates the
      timing errors of the approximations made. These errors are low enough to allow
      use of the new technique in most NDE and some specific medical applications. The
      new technique is validated by simulation and experimentally.

PMID- 23549535
TI  - On the nonlinear behavior of a multilayer circular piezoelectric plate-like
      transformer operating near resonance.
AB  - We studied the weakly nonlinear behaviors of a simply-supported multilayer
      circular piezoelectric plate-like transformer (MCPPT) operating near resonance,
      where the MCPPT consists of a multilayer circular piezoelectric compound plate
      with four piezoelectric layers polarized in different directions. Nonlinear
      effects of large deformations near resonance are considered; it is shown that on
      one side of the resonant frequency, the output-input relation becomes nonlinear,
      and the other side, the output voltage becomes multivalued.

PMID- 23549536
TI  - On the precision of time-of-flight shear wave speed estimation in homogeneous
      soft solids: initial results using a matrix array transducer.
AB  - A system capable of tracking radiation-force-induced shear wave propagation in a
      3-D volume using ultrasound is presented. In contrast to existing systems, which
      use 1-D array transducers, a 2-D matrix array is used for tracking shear wave
      displacements. A separate single-element transducer is used for radiation force
      excitation. This system allows shear wave propagation in all directions away from
      the push to be observed. It is shown that for a limit of 64 tracking beams, by
      placing the beams at the edges of the measurement region of interest (ROI) at
      multiple directions from the push, time-of- flight (TOF) shear wave speed (SWS)
      measurement uncertainty can theoretically be reduced by 40% compared with equally
      spacing the tracking beams within the ROI along a single plane, as is typical
      when using a 1-D array for tracking. This was verified by simulation, and a
      reduction of 30% was experimentally observed on a homogeneous phantom. Analytical
      expressions are presented for the relationship between TOF SWS measurement
      uncertainty and various shear wave imaging parameters. It is shown that TOF SWS
      uncertainty is inversely proportional to ROI size, and inversely proportional to
      the square root of the number of tracking locations for a given distribution of
      beam locations relative to the push. TOF SWS uncertainty is shown to increase
      with the square of the SWS, indicating that TOF SWS measurements are
      intrinsically less precise for stiffer materials.

PMID- 23549537
TI  - Anti-symmetric flexural modes for the detection of humidity variation.
AB  - Antisymmetric flexural (ASF) modes are guided acoustic modes propagating along
      the apex line of a wedge with particle motion that is antisymmetric about the
      midplane bisecting the apex angle. This paper describes experimental observations
      in applying ASF modes for the detection of moisture variation. In our setup, the
      wedge tip is coated with a thin layer of hygroscopic film for the absorption of
      moisture, so the phase velocity of the ASF mode is influenced by the changing
      humidity of the surrounding air. Enhanced by the wedge tip geometry, mass-loading
      effects on the ASF velocity resulting from the absorption of humidity are
      pronounced in a low-frequency regime of 0.2 to 2.0 MHz. Numerical models based on
      finite element analysis are constructed to explain the humidity sensing
      mechanism.

PMID- 23549538
TI  - A rectangle-type linear ultrasonic motor using longitudinal vibration transducers
      with four driving feet.
AB  - To make full use of the vibrational energy of a longitudinal transducer, a
      rectangle-type linear ultrasonic motor with four driving feet is proposed in this
      paper. This new motor consists of four longitudinal vibration transducers which
      are arranged in a rectangle and form an enclosed construction. Lead zirconate
      titanate ceramics are embedded into the middle of the transducer and fastened by
      a wedge-caulking mechanism. Each transducer includes an exponentially shaped horn
      located on each end. The horns of the vertical transducers intersect at the base
      of the horizontal transducers' horns; the tip ends of the horizontal transducers'
      horns are used as the driving feet. Longitudinal vibrations are superimposed in
      the motor and generate elliptical movements at the tip ends of the horns. The
      working principle of the proposed motor is analyzed. The resonance frequencies of
      two working modes are tuned to be close to each other by adjusting the structural
      parameters. Transient analysis is developed to gain the vibration characteristics
      of the motor. A prototype motor is fabricated and measured. The vibration test
      results verify the feasibility of the proposed design. Typical output of the
      prototype is a no-load speed of 928 mm/s and maximum thrust force of 60 N at a
      voltage of 200 Vrms.

PMID- 23549539
TI  - Efficiency improvement of hybrid transducer-type ultrasonic motor using
      lubricant.
AB  - Ultrasonic motors have hit a bottleneck caused by low efficiency and short life,
      which limits their applications to some niche areas. We believe that lubrication
      is a promising candidate to solve these problems. In this paper, we clarify, both
      analytically and experimentally, that the performance of the hybrid transducer
      type ultrasonic motor (HTUSM), including the transduction efficiency, can be
      drastically improved at large static preloads if appropriate lubricant is
      applied. First, simulation was performed using an equivalent circuit in dry and
      lubricated conditions, and the HTUSM characteristics were shown to be more
      desirable at high static preloads in the lubricated condition than in the dry
      condition. Then, we experimentally investigated the mechanical performance of the
      HTUSM, verifying the effect of improving the motor performance at high preloads
      using lubricant, which was in good agreement with the simulation results. The
      maximum transduction efficiency of the HTUSM was significantly enhanced from 28%
      in the dry condition to 68% in the lubricated condition.

PMID- 23549540
TI  - Impedance of DC-bias-controlled composite FBARs.
AB  - A closed-form analytic formula is derived for composite resonators consisting of
      two layers of paraelectricphase ferroelectrics. It is used to analyze the
      properties of these resonators. Under an applied dc electric field, the layers
      exhibit an induced piezoelectric effect. The signs of the induced piezoelectric
      coefficients may be changed by changing the polarity of the dc voltages applied
      to the layers. In the case of a composite in which the layers have similar
      thicknesses, changing the sign of the piezoelectric coefficient causes a
      switching between the resonant frequencies of the first and second harmonics. In
      the case in which one of the layers is substantially thinner, changing the sign
      of the piezoelectric coefficient causes switching of the resonant frequency of
      the first harmonic between two values. In both cases, a continuous change in the
      dc bias voltage causes continuous changes in the resonant frequencies.

PMID- 23549541
TI  - High-precision signal processing algorithm to evaluate SAW properties as a
      function of temperature.
AB  - This paper presents a signal processing algorithm which accurately evaluates the
      SAW properties of a substrate as functions of temperature. The investigated
      acoustic properties are group velocity, phase velocity, propagation loss, and
      coupling coefficient. With several measurements carried out at different
      temperatures, we obtain the temperature dependency of the SAW properties. The
      analysis algorithm starts by reading the transfer functions of short and long
      delay lines. The analysis algorithm determines the center frequency of the delay
      lines and obtains the delay time difference between the short and long delay
      lines. The extracted parameters are then used to calculate the acoustic
      properties of the SAW material. To validate the algorithm, its accuracy is
      studied by determining the error in the calculating delay time difference, center
      frequency, and group velocity.

PMID- 23549542
TI  - Experimental and theoretical investigations of some useful langasite cuts for
      high-temperature SAW applications.
AB  - Passive high-temperature sensors are a most promising area of use for SAW
      devices. Langasite (La3Ga5SiO14; LGS) has been identified as promising
      piezoelectric material to meet high-temperature SAW challenges. Because it is
      necessary to know the material behavior for an accurate device design, the
      frequency?temperature behavior of Rayleigh SAW (R-SAW) and shear-horizontal SAW
      (SH-SAW) LGS cuts is investigated on delay line and resonator test structures up
      to 700 degrees C by RF characterization. In the range of the 434-MHz ISM band,
      the (0 degrees , 22 degrees , 90 degrees ) SH-SAW cut shows thermal behavior
      similar to the (0 degrees , 138.5 degrees , 26.7 degrees ) R-SAW cut. Associated
      with the (0 degrees , 22 degrees , 31 degrees ) cut, in which SAWs present mixed
      types of polarization, the (0 degrees , 22 degrees , 90 degrees ) SH-SAW
      orientation might allow differential measurements on a single substrate. In the
      temperature range of 400 to 500 degrees C, delay line test devices using the SH
      SAW cut show a considerable drop of signal. Theoretical analysis indicates that
      this newly described behavior might be a result of anisotropy effects in this
      cut, occurring in case of any slight misorientation of electrode alignment.

PMID- 23549543
TI  - A full set of langatate high-temperature acoustic wave constants: elastic,
      piezoelectric, dielectric constants up to 900 degrees C.
AB  - A full set of langatate (LGT) elastic, dielectric, and piezoelectric constants
      with their respective temperature coefficients up to 900 degrees C is presented,
      and the relevance of the dielectric and piezoelectric constants and temperature
      coefficients are discussed with respect to predicted and measured high
      temperature SAW propagation properties. The set of constants allows for high
      temperature acoustic wave (AW) propagation studies and device design. The
      dielectric constants and polarization and conductive losses were extracted by
      impedance spectroscopy of parallel-plate capacitors. The measured dielectric
      constants at high temperatures were combined with previously measured LGT
      expansion coefficients and used to determine the elastic and piezoelectric
      constants using resonant ultrasound spectroscopy (RUS) measurements at
      temperatures up to 900 degrees C. The extracted LGT piezoelectric constants and
      temperature coefficients show that e11 and e14 change by up to 62% and 77%,
      respectively, for the entire 25 degrees C to 900 degrees C range when compared
      with room-temperature values. The LGT high-temperature constants and temperature
      coefficients were verified by comparing measured and predicted phase velocities
      (vp) and temperature coefficients of delay (TCD) of SAW delay lines fabricated
      along 6 orientations in the LGT plane (90 degrees , 23 degrees , Psi) up to 900
      degrees C. For the 6 tested orientations, the predicted SAW vp agree within 0.2%
      of the measured vp on average and the calculated TCD is within 9.6 ppm/ degrees C
      of the measured value on average over the temperature range of 25 degrees C to
      900 degrees C. By including the temperature dependence of both dielectric and
      piezoelectric constants, the average discrepancies between predicted and measured
      SAW properties were reduced, on average: 77% for vp, 13% for TCD, and 63% for the
      turn-over temperatures analyzed.

PMID- 23549544
TI  - An improved analytical method to design CMUTs with square diaphragms.
AB  - A highly accurate mathematical method has been presented for analytical
      characterization of capacitive micromachined ultrasonic transducers (CMUTs) built
      with square diaphragms. The method uses a new two-dimensional polynomial function
      to more accurately predict the deflection curve of a multilayer square diaphragm
      subject to both mechanical and electrostatic pressure and a new capacitance model
      that takes into account the contribution of the fringing field capacitances. Both
      of the models have been experimentally verified by comparing the models predicted
      values with measurement results and are found to be in excellent agreement with a
      maximum deviation of less than 2% for experimentally measured capacitance values.
      3-D electromechanical finite element analysis (FEA) for a wide range of material
      properties, geometric specifications, and loading conditions show that the
      presented method is highly consistent in accuracy over the typical square
      diaphragm CMUT design space.

PMID- 23549545
TI  - A piezoelectric spring-mass system as a low-frequency energy harvester.
AB  - We propose a new structure consisting of a piezoelectric spring-mass system as a
      low-frequency piezoelectric energy harvester. A theoretical model is developed
      for the system from the theory of piezoelectricity. An analysis is performed to
      demonstrate the low-frequency nature of the system. Other basic characteristics
      of the energy harvester, including the output power, voltage, and efficiency, are
      also calculated and examined.

PMID- 23549546
TI  - The low-power potential of oven-controlled MEMS oscillators.
AB  - It is shown that oven-controlled micro electromechanical systems (MEMS)
      oscillators have the potential of attaining a higher frequency stability, with a
      lower power consumption, than temperature-compensated crystal oscillators (TCXOs)
      and the currently manufactured MEMS oscillators.

PMID- 23549547
TI  - New fabrication of high-frequency (100-MHz) ultrasound PZT film kerfless linear
      array.
AB  - The paper describes the design, fabrication, and measurements of a high-frequency
      ultrasound kerfless linear array prepared from hydrothermal lead zirconate
      titanate (PZT) thick film. The 15-MUm hydrothermal PZT thick film with an area of
      1 * 1 cm, obtained through a self-separation process from Ti substrate, was used
      to fabricate a 32-element 100-MHz kerfless linear array with photolithography.
      The bandwidth at -6 dB without matching layer, insertion loss around center
      frequency, and crosstalk between adjacent elements were measured to be 39%, -30
      dB, and -15 dB, respectively.

PMID- 23549548
TI  - Overtone frequency spectra for x3-dependent modes in AT-cut quartz resonators.
AB  - We study straight-crested waves and vibration modes with spatial variations along
      the x3 direction only in an AT-cut quartz plate resonator. The equations of
      anisotropic elasticity are used. Dispersion relations for face-shear and
      thickness-twist waves in unbounded plates are plotted. Frequency spectra are
      obtained for face-shear and thickness-twist vibrations of finite plates in which
      these modes are coupled by boundary conditions. Most importantly, our analysis
      produces the frequency spectra for overtone modes which do not seem to have been
      obtained before for x3-dependent modes. Numerical results for third- and fifth
      overtone AT-cut quartz resonators are presented, showing that higher-order
      overtone modes are associated with more mode couplings.

PMID- 23549549
TI  - Lateral-field-excited bulk acoustic wave sensors on langasite working on
      different operational modes.
AB  - Lateral-field-excited (LFE) bulk acoustic wave sensors on langasite working on
      different operational modes are investigated and compared. Langasite LFE sensors
      on pure-LFE mode and pseudo-LFE mode are designed and fabricated. The
      sensitivities of the devices to changes in liquid electrical properties (e.g.,
      conductivity or permittivity) and micro-mass changes on their surfaces were
      tested and compared. The experimental results show that compared with langasite
      pure-LFE devices, langasite pseudo-LFE devices have superior sensitivities to
      both liquid conductivity and liquid permittivity changes. For the micro-mass
      changes, the pure- LFE devices showed high sensitivity, whereas the pseudo-LFE
      devices do not, because they cannot resonate in air. On this basis, the physical
      interpretation of these results is discussed.

PMID- 23549550
TI  - The impact of PET/CT imaging performed in the early postoperative period on the
      management of breast cancer patients.
AB  - OBJECTIVES: The aim of the study was to evaluate the role of F-fluorodeoxyglucose
      ((18)F-FDG) PET/computed tomography (CT) in the early postoperative staging of
      breast cancer and to document (18)F-FDG PET/CT-based stage alterations and any
      subsequent impact on management. MATERIALS AND METHODS: Between January 2009 and
      June 2012, PET/CT images of patients with histopathologically proven breast
      cancer who underwent surgery with no previous chemotherapy or radiotherapy were
      retrospectively reviewed. Any stage alteration due to a change in nodal or
      metastatic status on PET/CT was noted. RESULTS: A total of 77 women (median age:
      52 years; range: 26-87 years) were included. PET/CT revealed distant metastases
      that were previously undetected in 12 of the 77 women (15.6%). Of these women,
      one (8.3%) was diagnosed with stage I, four (33.3%) with stage II, and seven
      (58.4%) with stage III disease before the PET study. In two patients, lung
      lesions were diagnosed as metastases by conventional imaging methods, and in one
      patient the lesions were revealed to have a low probability for malignancy on
      PET/CT, and they were confirmed as benign on follow-up CT. Thus, changes in
      disease stage occurred in 15 of 77 (19.5%) patients following PET/CT. The disease
      was upstaged in 14 patients (18.2%) and downstaged in one (1.3%). CONCLUSION: The
      impact of (18)F-FDG PET/CT is highest in newly diagnosed stage III breast cancer
      because of the identification of previously undetected extra-axillary lymph nodes
      and distant metastases. Early postoperative (18)F-FDG PET/CT imaging may alter
      the staging and potentially contribute to the management of these patients.

PMID- 23549551
TI  - Role of 18F-FDG PET/CT in identifying distant metastatic disease missed by
      conventional imaging in patients with locally advanced breast cancer.
AB  - OBJECTIVES: This study was conducted to evaluate the role of (18)F
      fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) in identifying missed
      distant metastases in patients with locally advanced breast cancer (LABC) who
      were assessed by conventional imaging methods. MATERIALS AND METHODS: Forty-three
      consecutive patients with histopathologically proven LABC with negative
      conventional imaging results for distant metastases were included in the study.
      All of them underwent (18)F-FDG PET/CT within a week after conventional imaging.
      RESULTS: (18)F-FDG PET/CT findings suggestive of distant metastases were noted in
      11/43 patients, and 10 of them were confirmed to have true-positive distant
      metastatic disease on clinical follow-up of 6 months. None of the patients with
      negative (18)F-FDG PET/CT for distant metastases developed distant metastases
      during the follow-up. (18)F-FDG PET/CT had a sensitivity, specificity, positive
      predictive value, and negative predictive value of 100, 96.8, 91, and 100%,
      respectively, for identifying distant metastases missed by conventional imaging.
      In addition, (18)F-FDG PET/CT suggested previously unknown lymph nodal metastases
      in 16/43 (37%) patients. Change in stage was noticed in 17/43 (39.5%) patients.
      CONCLUSION: (18)F-FDG PET/CT is a sensitive and specific imaging modality for
      identifying distant metastases in patients with LABC missed by conventional
      imaging. In addition, it detects unknown lymph nodal metastases in a significant
      proportion of patients and hence can be used routinely in staging of patients
      with LABC.

PMID- 23549556
TI  - The cover. Filles de Kilimanjaro III (Miles Davis).

PMID- 23549553
TI  - A Novel Adenoviral Hybrid-vector System Carrying a Plasmid Replicon for Safe and
      Efficient Cell and Gene Therapeutic Applications.
AB  - In dividing cells, the two aims a gene therapeutic approach should accomplish are
      efficient nuclear delivery and retention of therapeutic DNA. For stable transgene
      expression, therapeutic DNA can either be maintained by somatic integration or
      episomal persistence of which the latter approach would diminish the risk of
      insertional mutagenesis. As most monosystems fail to fulfill both tasks with
      equal efficiency, hybrid-vector systems represent promising alternatives. Our
      hybrid-vector system synergizes high-capacity adenoviral vectors (HCAdV) for
      efficient delivery and the scaffold/matrix attachment region (S/MAR)-based pEPito
      plasmid replicon for episomal persistence. After proving that this plasmid
      replicon can be excised from adenovirus in vitro, colony forming assays were
      performed. We found an increased number of colonies of up to sevenfold in cells
      that received the functional plasmid replicon proving that the hybrid-vector
      system is functional. Transgene expression could be maintained for 6 weeks and
      the extrachromosomal plasmid replicon was rescued. To show efficacy in vivo, the
      adenoviral hybrid-vector system was injected into C57Bl/6 mice. We found that the
      plasmid replicon can be released from adenoviral DNA in murine liver resulting in
      long-term transgene expression. In conclusion, we demonstrate the efficacy of our
      novel HCAdV-pEPito hybrid-vector system in vitro and in vivo.Molecular Therapy
      Nucleic Acids (2013) 2, e83; doi:10.1038/mtna.2013.11; published online 2 April
      2013.

PMID- 23549558
TI  - President Wilson rises to an emergency.

PMID- 23549559
TI  - IOM: Curbing fake drugs will require national tracking and global teamwork.

PMID- 23549560
TI  - Cutting Medicare costs will require multipronged approach.

PMID- 23549561
TI  - More patients get good diabetes control, but only a minority meet all goals.

PMID- 23549569
TI  - Measures to define chronic kidney disease.

PMID- 23549570
TI  - Measures to define chronic kidney disease--reply.

PMID- 23549571
TI  - Exposure on September 11, 2001, and cancer risk.

PMID- 23549572
TI  - Exposure on September 11, 2001, and cancer risk--reply.

PMID- 23549573
TI  - Iodine supplements during and after pregnancy.

PMID- 23549574
TI  - Iodine supplements during and after pregnancy.

PMID- 23549575
TI  - Iodine supplements during and after pregnancy--reply.

PMID- 23549577
TI  - Venous thrombosis related to air travel.

PMID- 23549578
TI  - Venous thrombosis related to air travel--reply.

PMID- 23549579
TI  - The inevitable application of big data to health care.

PMID- 23549580
TI  - A piece of my mind. The clock doctor.

PMID- 23549582
TI  - Effect of an investigational vaccine for preventing Staphylococcus aureus
      infections after cardiothoracic surgery: a randomized trial.
AB  - IMPORTANCE: Infections due to Staphylococcus aureus are serious complications of
      cardiothoracic surgery. A novel vaccine candidate (V710) containing the highly
      conserved S. aureus iron surface determinant B is immunogenic and generally well
      tolerated in volunteers. OBJECTIVE: To evaluate the efficacy and safety of
      preoperative vaccination in preventing serious postoperative S. aureus infection
      in patients undergoing cardiothoracic surgery. DESIGN, SETTING, AND PARTICIPANTS:
      Double-blind, randomized, event-driven trial conducted between December 2007 and
      August 2011 among 8031 patients aged 18 years or older who were scheduled for
      full median sternotomy within 14 to 60 days of vaccination at 165 sites in 26
      countries. INTERVENTION: Participants were randomly assigned to receive a single
      0.5-mL intramuscular injection of either V710 vaccine, 60 MUg (n = 4015), or
      placebo (n = 4016). MAIN OUTCOME MEASURES: The primary efficacy end point was
      prevention of S. aureus bacteremia and/or deep sternal wound infection (including
      mediastinitis) through postoperative day 90. Secondary end points included all S.
      aureus surgical site and invasive infections through postoperative day 90. Three
      interim analyses with futility assessments were planned. RESULTS: The independent
      data monitoring committee recommended termination of the study after the second
      interim analysis because of safety concerns and low efficacy. At the end of the
      study, the V710 vaccine was not significantly more efficacious than placebo in
      preventing either the primary end points (22/3528 V710 vaccine recipients [2.6
      per 100 person-years] vs 27/3517 placebo recipients [3.2 per 100 person-years];
      relative risk, 0.81; 95% CI, 0.44-1.48; P = .58) or secondary end points despite
      eliciting robust antibody responses. Compared with placebo, the V710 vaccine was
      associated with more adverse experiences during the first 14 days after
      vaccination (1219/3958 vaccine recipients [30.8%; 95% CI, 29.4%-32.3%] and
      866/3967 placebo recipients [21.8%; 95% CI, 20.6%-23.1%], including 797 [20.1%;
      95% CI, 18.9%-21.4%] and 378 [9.5%; 95% CI, 8.6%-10.5%] with injection site
      reactions and 66 [1.7%; 95% CI, 1.3%-2.1%] and 51 [1.3%; 95% CI, 1.0%-1.7%] with
      serious adverse events, respectively) and a significantly higher rate of
      multiorgan failure during the entire study (31 vs 17 events; 0.9 [95% CI, 0.6
      1.2] vs 0.5 [95% CI, 0.3-0.8] events per 100 person-years; P = .04). Although the
      overall incidence of vaccine-related serious adverse events (1 in each group) and
      the all-cause mortality rate (201/3958 vs 177/3967; 5.7 [95% CI, 4.9-6.5] vs 5.0
      [95% CI, 4.3-5.7] deaths per 100 person-years; P = .20) were not statistically
      different between groups, the mortality rate in patients with staphylococcal
      infections was significantly higher among V710 vaccine than placebo recipients
      (15/73 vs 4/96; 23.0 [95% CI, 12.9-37.9] vs 4.2 [95% CI, 1.2-10.8] per 100 person
      years; difference, 18.8 [95% CI, 8.0-34.1] per 100 person-years). CONCLUSIONS AND
      RELEVANCE: Among patients undergoing cardiothoracic surgery with median
      sternotomy, the use of a vaccine against S. aureus compared with placebo did not
      reduce the rate of serious postoperative S. aureus infections and was associated
      with increased mortality among patients who developed S. aureus infections. These
      findings do not support the use of the V710 vaccine for patients undergoing
      surgical interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00518687.

PMID- 23549581
TI  - Effect of duloxetine on pain, function, and quality of life among patients with
      chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial.
AB  - IMPORTANCE: There are no known effective treatments for painful chemotherapy
      induced peripheral neuropathy. OBJECTIVE: To determine the effect of duloxetine,
      60 mg daily, on average pain severity. DESIGN, SETTING, AND PATIENTS: Randomized,
      double-blind, placebo-controlled crossover trial at 8 National Cancer Institute
      (NCI)-funded cooperative research networks that enrolled 231 patients who were 25
      years or older being treated at community and academic settings between April
      2008 and March 2011. Study follow-up was completed July 2012. Stratified by
      chemotherapeutic drug and comorbid pain risk, patients were randomized to receive
      either duloxetine followed by placebo or placebo followed by duloxetine.
      Eligibility required that patients have grade 1 or higher sensory neuropathy
      according to the NCI Common Terminology Criteria for Adverse Events and at least
      4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after
      paclitaxel, other taxane, or oxaliplatin treatment. INTERVENTIONS: The initial
      treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or
      placebo for the first week and 2 capsules of either 30 mg of duloxetine or
      placebo daily for 4 additional weeks. MAIN OUTCOME MEASURES: The primary
      hypothesis was that duloxetine would be more effective than placebo in decreasing
      chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed
      using the Brief Pain Inventory-Short Form "average pain" item with 0 representing
      no pain and 10 representing as bad as can be imagined. RESULTS: Individuals
      receiving duloxetine as their initial 5-week treatment reported a mean decrease
      in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among
      those who received placebo (P = .003; effect size, 0.513). The observed mean
      difference in the average pain score between duloxetine and placebo was 0.73 (95%
      CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38%
      of those initially receiving placebo reported decreased pain of any amount.
      CONCLUSION AND RELEVANCE: Among patients with painful chemotherapy-induced
      peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks
      resulted in a greater reduction in pain. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00489411.

PMID- 23549583
TI  - Mortality rates for Medicare beneficiaries admitted to critical access and non
      critical access hospitals, 2002-2010.
AB  - IMPORTANCE: Critical access hospitals (CAHs) provide inpatient care to Americans
      living in rural communities. These hospitals are at high risk of falling behind
      with respect to quality improvement, owing to their limited resources and
      vulnerable patient populations. How they have fared on patient outcomes during
      the past decade is unknown. OBJECTIVE: To evaluate trends in mortality for
      patients receiving care at CAHs and compare these trends with those for patients
      receiving care at non-CAHs. DESIGN, SETTING, AND PATIENTS: Retrospective
      observational study using data from Medicare fee-for-service patients admitted to
      US acute care hospitals with acute myocardial infarction (1,902,586 admissions),
      congestive heart failure (4,488,269 admissions), and pneumonia (3,891,074
      admissions) between 2002 and 2010. MAIN OUTCOME MEASURES: Trends in risk-adjusted
      30-day mortality rates for CAHs and other acute care US hospitals. RESULTS:
      Accounting for differences in patient, hospital, and community characteristics,
      CAHs had mortality rates comparable with those of non-CAHs in 2002 (composite
      mortality across all 3 conditions, 12.8% vs 13.0%; difference, -0.3% [95% CI, 
      0.7% to 0.2%]; P = .25). Between 2002 and 2010, mortality rates increased 0.1%
      per year in CAHs but decreased 0.2% per year in non-CAHs, for an annual
      difference in change of 0.3% (95% CI, 0.2% to 0.3%; P < .001). Thus, by 2010,
      CAHs had higher mortality rates compared with non-CAHs (13.3% vs 11.4%;
      difference, 1.8% [95% CI, 1.4% to 2.2%]; P < .001). The patterns were similar
      when each individual condition was examined separately. Comparing CAHs with other
      small, rural hospitals, similar patterns were found. CONCLUSIONS AND RELEVANCE:
      Among Medicare beneficiaries with acute myocardial infarction, congestive heart
      failure, or pneumonia, 30-day mortality rates for those admitted to CAHs,
      compared with those admitted to other acute care hospitals, increased from 2002
      to 2010. New efforts may be needed to help CAHs improve.

PMID- 23549584
TI  - Melatonin secretion and the incidence of type 2 diabetes.
AB  - IMPORTANCE: Loss-of-function mutations in the melatonin receptor are associated
      with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional
      analysis of persons without diabetes, lower nocturnal melatonin secretion was
      associated with increased insulin resistance. OBJECTIVE: To study the association
      between melatonin secretion and the risk of developing type 2 diabetes. DESIGN,
      SETTING, AND PARTICIPANTS: Case-control study nested within the Nurses' Health
      Study cohort. Among participants without diabetes who provided urine and blood
      samples at baseline in 2000, we identified 370 women who developed type 2
      diabetes from 2000-2012 and matched 370 controls using risk-set sampling. MAIN
      OUTCOME MEASURES: Associations between melatonin secretion at baseline and
      incidence of type 2 diabetes were evaluated with multivariable conditional
      logistic regression controlling for demographic characteristics, lifestyle
      habits, measures of sleep quality, and biomarkers of inflammation and endothelial
      dysfunction. RESULTS: The median urinary ratios of 6-sulfatoxymelatonin to
      creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3
      ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of
      6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable
      odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio
      of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio
      category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had
      a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2
      diabetes. Women in the highest category of melatonin secretion had an estimated
      diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27
      cases/1000 person-years in the lowest category. CONCLUSIONS AND RELEVANCE: Lower
      melatonin secretion was independently associated with a higher risk of developing
      type 2 diabetes. Further research is warranted to assess if melatonin secretion
      is a modifiable risk factor for diabetes within the general population.

PMID- 23549586
TI  - Fall prevention in community-dwelling older adults.
AB  - CLINICAL QUESTION: Which types of interventions reduce falls in older people
      living in the community? BOTTOM LINE: Fall-prevention exercise programs, usually
      including muscle strengthening and balance retraining, were associated with lower
      fall rates in community-dwelling older people whether or not individuals were
      selected on the basis of fall risk. Home safety interventions, vitamin D
      supplementation in people with lower vitamin D levels, and individually targeted
      multifactorial interventions were associated with fewer falls in community
      dwelling people with risk factors for falling.

PMID- 23549585
TI  - Management of human immunodeficiency virus infection in advanced age.
AB  - IMPORTANCE: Human immunodeficiency virus (HIV)-positive patients treated with
      antiretroviral therapy now have increased life expectancy and develop chronic
      illnesses that are often seen in older HIV-negative patients. OBJECTIVE: To
      address emerging issues related to aging with HIV. Screening older adults for
      HIV, diagnosis of concomitant diseases, management of multiple comorbid medical
      illnesses, social isolation, polypharmacy, and factors associated with end-of
      life care are reviewed. EVIDENCE ACQUISITION: Published guidelines and consensus
      statements were reviewed. PubMed and PsycINFO were searched between January 2000
      and February 2013. Articles not appearing in the search that were referenced by
      reviewed articles were also evaluated. FINDINGS: The population of older HIV
      positive patients is rapidly expanding. It is estimated that by 2015 one-half of
      the individuals in the United States with HIV will be older than age 50. Older
      HIV-infected patients are prone to having similar chronic diseases as their HIV
      negative counterparts, as well as illnesses associated with co-infections.
      Medical treatments associated with these conditions, when added to an
      antiretroviral regimen, increase risk for polypharmacy. Care of aging HIV
      infected patients involves a need to balance a number of concurrent comorbid
      medical conditions. CONCLUSIONS AND RELEVANCE: HIV is no longer a fatal disease.
      Management of multiple comorbid diseases is a common feature associated with
      longer life expectancy in HIV-positive patients. There is a need to better
      understand how to optimize the care of these patients.

PMID- 23549587
TI  - Preventing postoperative Staphylococcus aureus infections: the search continues.

PMID- 23549588
TI  - Are mortality differences detected by administrative data reliable and
      actionable?

PMID- 23549589
TI  - JAMA patient page. Statins.

PMID- 23549590
TI  - A two-photon fluorescent probe with near-infrared emission for hydrogen sulfide
      imaging in biosystems.
AB  - Hydrogen sulfide (H2S) is emerging as an important gasotransmitter but remains
      difficult to study. Here we report a novel two-photon fluorescent probe with NIR
      emission for H2S detection. It was successfully used to realize H2S imaging in
      bovine serum, living cells, tissues as well as in living mice.

PMID- 23549591
TI  - On the levels.

PMID- 23549593
TI  - Does snowboarding increase overall injury risk on ski slopes? Letter to the
      editor.

PMID- 23549594
TI  - Risk of reinjury after ACL reconstruction: letter to the editor.

PMID- 23549595
TI  - Return to sport after injury rehabilitation: letter to the editor.

PMID- 23549596
TI  - Return to sport after anterior cruciate ligament reconstruction: letter to the
      editor.

PMID- 23549598
TI  - Comparison of southern Chinese Han and Brazilian Caucasian mutation rates at
      autosomal short tandem repeat loci used in human forensic genetics.
AB  - The short tandem repeat (STR) loci used in human genetic studies are
      characterized by having relatively high mutation rates. In particular, to ensure
      an appropriate evaluation of genetic evidence in parentage and forensic analyses,
      it is essential to have accurate estimates of the mutation rates associated with
      the commonly used autosomal and sex chromosome STR loci. Differences in STR
      mutation rates between different ethnic groups should also be determined.
      Mutation data from two laboratories working with different ethnic groups were
      extracted from many meiotic transmissions ascertained for 15 autosomal STR loci
      currently used in forensic routine. Forty-five thousand and eighty-five trios
      were checked for the biological consistency of maternity and paternity through
      the analysis of a minimum of 15 loci. Mutations were scored as paternal,
      maternal, or ambiguous according to the most parsimonious explanation for the
      inconsistency, using always the least requiring hypothesis in terms of number of
      repeat differences. The main findings are: (a) the overall mutation rate across
      the 15 loci was 9.78 * 10(-4) per gamete per generation (95% CI = 9.30 * 10(-4)
      1.03 * 10(-3)), and with just 48 (out of 1,587) exceptions, all of the mutations
      were single-step; (b) repeat gains were more frequent than losses; (c) longer
      alleles were found to be more mutable; and (d) the mutation rates differ at some
      loci between the two ethnic groups. Large worldwide meiotic transmission datasets
      are still needed to measure allele-specific mutation rates at the STR loci
      consensually used in forensic genetics.

PMID- 23549599
TI  - Therapeutic effects of NK-HDAC-1, a novel histone deacetylase inhibitor, on
      collagen-induced arthritis through the induction of apoptosis of fibroblast-like
      synoviocytes.
AB  - The purpose of this study is to investigate the therapeutic effects of a novel
      histone deacetylase inhibitor (HDACi), NK-HDAC-1, on collagen-induced arthritis
      (CIA) and pathogenic fibroblast-like synoviocytes (FLSs) from patients with
      rheumatoid arthritis (RA). The proliferation and apoptosis of FLSs treated with
      NK-HDAC-1 were evaluated by flow cytometry and fluorescence staining. The effect
      of NK-HDAC-1 treatment on pro-inflammatory cytokine production was determined by
      ELISA. CIA was established in DBA/1 mice, and NK-HDAC-1 or vehicle was
      administered daily after the onset of arthritis. Clinical and histological scores
      were calculated to assess the therapeutic efficacy of NK-HDAC-1. NK-HDAC-1
      significantly inhibited the proliferation of FLSs through cell cycle arrest at
      the G2/M checkpoint and enhanced apoptosis of FLSs. The activity of caspases was
      increased during NK-HDAC-1 treatment. IL-6 production by FLSs was also suppressed
      by NK-HDAC-1. Furthermore, the oral administration of NK-HDAC-1 significantly
      enhanced synoviocyte apoptosis in vivo and inhibited CIA progression. Compared
      with subcroylanilide hydroxamic acid which exhibited moderate prophylactic
      efficacy, NK-HDAC-1 demonstrated therapeutic efficacy in CIA. NK-HDAC-1 is a
      novel HDACi that may ameliorate inflammatory arthritis by regulating the
      activation, apoptosis, and inflammatory responses of FLSs. This is the first
      study to support that NK-HDAC-1 may be a potential therapeutic agent for RA. 

PMID- 23549600
TI  - We are producers of patient value and financial value.

PMID- 23549601
TI  - Current world literature. Retinal, vitreous and macular disorders.

PMID- 23549603
TI  - Excemplify: a flexible template based solution, parsing and managing data in
      spreadsheets for experimentalists.
AB  - In systems biology, quantitative experimental data is the basis of building
      mathematical models. In most of the cases, they are stored in Excel files and
      hosted locally. To have a public database for collecting, retrieving and citing
      experimental raw data as well as experimental conditions is important for both
      experimentalists and modelers. However, the great effort needed in the data
      handling procedure and in the data submission procedure becomes the crucial
      limitation for experimentalists to contribute to a database, thereby impeding the
      database to deliver its benefit. Moreover, manual copy and paste operations which
      are commonly used in those procedures increase the chance of making mistakes.
      Excemplify, a web-based application, proposes a flexible and adaptable template
      based solution to solve these problems. Comparing to the normal template based
      uploading approach, which is supported by some public databases, rather than
      predefining a format that is potentiall impractical, Excemplify allows users to
      create their own experiment-specific content templates in different experiment
      stages and to build corresponding knowledge bases for parsing. Utilizing the
      embedded knowledge of used templates, Excemplify is able to parse experimental
      data from the initial setup stage and generate following stages spreadsheets
      automatically. The proposed solution standardizes the flows of data traveling
      according to the standard procedures of applying the experiment, cuts down the
      amount of manual effort and reduces the chance of mistakes caused by manual data
      handling. In addition, it maintains the context of meta-data from the initial
      preparation manuscript and improves the data consistency. It interoperates and
      complements RightField and SEEK as well.

PMID- 23549604
TI  - A semi-automated approach for anatomical ontology mapping.
AB  - This paper presents a study in the domain of semi-automated and fully-automated
      ontology mapping. A process for inferring additional cross-ontology links within
      the domain of anatomical ontologies is presented and evaluated on pairs from
      three model organisms. The results of experiments performed with various external
      knowledge sources and scoring schemes are discussed.

PMID- 23549605
TI  - Preparation of Carboxylato-Coordinated Titanium Alkoxides from Carboxylic
      Anhydrides: Alkoxido Group Transfer from Metal Atom to Carbonyl Group.
AB  - Reaction of titanium(IV) isopropoxide, Ti(OiPr)4, with an equimolar amount of
      phthalic anhydride resulted in the transfer of an isopropoxido group from the
      metal atom to one carbonyl group of the anhydride and coordination of the thus
      formed monoester to the titanium atom. One monoester ligand in Ti2(OiPr)6(MU2-OOC
      C6H4-COOiPr)(eta1-OOC-C6H4-COOiPr)(iPrOH) is bridging and the other is eta1
      coordinated. When the reaction is performed in the presence of 1 mol-equiv. of
      acetic acid, the oxido cluster Ti6(MU3-O)6(OiPr)6(MU2-OOC-C6H4-COOiPr)6 was
      instead obtained. The MU3-oxygen groups in the latter compound are due to
      esterification of acetic acid by the cleaved isopropyl alcohol.

PMID- 23549606
TI  - Mechanochemical preparation of co-crystals.
AB  - The preparation of co-crystals via mechanochemistry combines the quest for clean
      and green processes with the investigation of multicomponent new materials, among
      the currently most fashionable systems in the crystal engineering field: the
      physico-chemical properties of the components add, merge or transform when co
      crystals are formed, giving rise to potentially improved performance in "old"
      solid-state chemistry fields, as in the pharmaceutical industry field, where they
      represent a way to obtain new formulations and to improve the properties
      (solubility, thermal stability, compressibility, etc.) of both new and existing
      drugs. 

PMID- 23549607
TI  - T1 measurements identify extracellular volume expansion in hypertrophic
      cardiomyopathy sarcomere mutation carriers with and without left ventricular
      hypertrophy.
AB  - BACKGROUND: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy
      (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere
      mutations seem to induce profibrotic changes before left ventricular hypertrophy
      (LVH) develops. To further evaluate these processes, we used cardiac magnetic
      resonance with T1 measurements on a genotyped HCM population to quantify
      myocardial extracellular volume (ECV). METHODS AND RESULTS: Sarcomere mutation
      carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH-, n=29), patients with
      HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11)
      underwent contrast cardiac magnetic resonance, measuring T1 times pre- and
      postgadolinium infusion. Concurrent echocardiography and serum biomarkers of
      collagen synthesis, hemodynamic stress, and myocardial injury were also available
      in a subset. Compared with controls, ECV was increased in patients with overt
      HCM, as well as G+/LVH- mutation carriers (ECV=0.36+/-0.01, 0.33+/-0.01, 0.27+/
      0.01 in G+/LVH+, G+/LVH-, controls, respectively; P<=0.001 for all comparisons).
      ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58;
      P<0.001) and global E' velocity (r=-0.48; P<0.001). Late gadolinium enhancement
      was present in >60% of overt patients with HCM but absent from G+/LVH- subjects.
      Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM
      than sarcomere-negative HCM. CONCLUSIONS: Myocardial ECV is increased in HCM
      sarcomere mutation carriers even in the absence of LVH. These data provide
      additional support that fibrotic remodeling is triggered early in disease
      pathogenesis. Quantifying ECV may help characterize the development of myocardial
      fibrosis in HCM and ultimately assist in developing novel disease-modifying
      therapy, targeting interstitial fibrosis.

PMID- 23549608
TI  - Genetic background of nonmutant Piebald-Virol-Glaxo rats does not influence
      nephronophthisis phenotypes.
AB  - BACKGROUND: Nephronophthisis (NPHP), which affects multiple organs, is a
      hereditary cystic kidney disease (CKD), characterized by interstitial fibrosis
      and numerous fluid-filled cysts in the kidneys. It is caused by mutations in NPHP
      genes, which encode for ciliary proteins known as nephrocystins. The disorder
      affects many people across the world and leads to end-stage renal disease. The
      aim of this study was to determine if the genetic background of the nonmutant
      female Piebald-Virol-Glaxo (PVG/Seac(-/-)) rat influences phenotypic inheritance
      of NPHP from mutant male Lewis polycystic kidney rats. METHODS: Mating
      experiments were performed between mutant Lewis polycystic kidney male rats with
      CKD and nonmutant PVG and Wistar Kyoto female rats without cystic kidney disease
      to raise second filial and backcross 1 progeny, respectively. Rats that developed
      cystic kidneys were identified. Systolic blood pressure was determined in each
      rat at 12 weeks of age using the tail and cuff method. After euthanasia, blood
      samples were collected and chemistry was determined. Histological examination of
      the kidneys, pancreas, and liver of rats with and without cystic kidney disease
      was performed. RESULTS: It was established that the genetic background of
      nonmutant female PVG rats did not influence the phenotypic inheritance of the CKD
      from mutant male Lewis polycystic kidney rats. The disease arose as a result of a
      recessive mutation in a single gene (second filial generation, CKD = 13, non-CKD
      = 39, chi (2) = 0.00, P >= 0.97; backcross 1 generation, CKD = 67, non-CKD = 72,
      chi (2) = 0.18, P > 0.05) and inherited as NPHP. The rats with CKD developed
      larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia,
      but there were no extrarenal cysts and disease did not lead to early pup
      mortality. CONCLUSION: The genetic background of the nonmutant PVG rats does not
      influence the genetic and phenotypic inheritance of CKD from mutant Lewis
      polycystic kidney rats. A single recessive mutation incapacitated the gene, which
      relaxed its functional constraints, and led to formation of multiple cysts in the
      kidneys of the homozygous mutant rats.

PMID- 23549609
TI  - Selective secretion of microRNA in CNS system.

PMID- 23549610
TI  - The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel":
      current effective inhibitor targeting a 3C-like protease.

PMID- 23549611
TI  - Pannexin-1 influences peritoneal cavity cell population but is not involved in
      NLRP3 inflammasome activation.
AB  - Pannexin-1 (Panx1) forms nonselective large channel in cell plasma membrane and
      has been shown to be associated with NLRP3 inflammasome activation, ATP release
      and phagocytes recruitment. In the current study, by manipulation of Panx1
      expression in human myeloid cells and application of Panx1 deficient mice, we
      failed to find a correlation between Panx1 and NLRP3 inflammasome activation,
      although an interaction between these two proteins was evident. However, in
      thioglycollate induced peritonitis, Panx1 deficient mice showed much more
      phagocytes infiltration. Further analyses showed that mice deficient for Panx1
      exhibited enlarged F4/80(low)Gr1(-)Ly6C(-)cell population in the peritonea. Our
      study thus reveals an important role for Panx1 in regulation of peritoneal cell
      population and peritonitis development.

PMID- 23549612
TI  - Regulation of tumor angiogenesis by the microtubule-binding protein CLIP-170.
AB  - Angiogenesis, the expansion of preexisting blood vessels, is a complex process
      required for tumor growth and metastasis. Although current antiangiogenic
      strategies have shown promising results in several cancer types, identification
      of additional antiangiogenic targets is required to improve the therapeutic
      response. Herein, we show that the microtubule-binding protein CLIP-170
      (cytoplasmic linker protein of 170 kDa) is highly expressed in breast tumor
      samples and correlates positively with blood vessel density. Depletion of CLIP
      170 significantly impaired vascular endothelial tube formation and sprouting in
      vitro and inhibited breast tumor growth in mice by decreasing tumor
      vascularization. Our data further show that CLIP-170 is important for the
      migration but not the proliferation of vascular endothelial cells. In addition,
      CLIP-170 promotes the polarization of endothelial cells in response to the
      angiogenic stimulus. These findings thus demonstrate a critical role for CLIP-170
      in tumor angiogenesis and suggest its potential as a novel antiangiogenic target.

PMID- 23549613
TI  - Structures of SdrD from Staphylococcus aureus reveal the molecular mechanism of
      how the cell surface receptors recognize their ligands.
AB  - Staphylococcus aureus is the most important Gram-positive colonizer of human skin
      and nasal passage, causing high morbidity and mortality. SD-repeat containing
      protein D (SdrD), an MSCRAMM (Microbial Surface Components Recognizing Adhesive
      Matrix Molecules) family surface protein, plays an important role in S. aureus
      adhesion and pathogenesis, while its binding target and molecular mechanism
      remain largely unknown. Here we solved the crystal structures of SdrD N2-N3
      domain and N2-N3-B1 domain. Through structural analysis and comparisons, we
      characterized the ligand binding site of SdrD, and proposed a featured sequence
      motif of its potential ligands. In addition, the structures revealed for the
      first time the interactions between B1 domain and N2-N3 domain among B domain
      containing MSCRAMMs. Our results may help in understanding the roles SdrD plays
      in S. aureus adhesion and shed light on the development of novel antibiotics.

PMID- 23549614
TI  - Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through
      calcium-induced dynamic interaction with neuronal nitric oxide synthase.
AB  - The activation and deactivation of Ca(2+)- and calmodulindependent neuronal
      nitric oxide synthase (nNOS) in the central nervous system must be tightly
      controlled to prevent excessive nitric oxide (NO) generation. Considering plasma
      membrane calcium ATPase (PMCA) is a key deactivator of nNOS, the present
      investigation aims to determine the key events involved in nNOS deactivation of
      by PMCA in living cells to maintain its cellular context. Using time-resolved
      Forster resonance energy transfer (FRET), we determined the occurrence of Ca(2+)
      induced protein-protein interactions between plasma membrane calcium ATPase 4b
      (PMCA4b) and nNOS in living cells. PMCA activation significantly decreased the
      intracellular Ca(2+) concentrations ([Ca(2+)]i), which deactivates nNOS and
      slowdowns NO synthesis. Under the basal [Ca(2+)]i caused by PMCA activation, no
      protein-protein interactions were observed between PMCA4b and nNOS. Furthermore,
      both the PDZ domain of nNOS and the PDZ-binding motif of PMCA4b were essential
      for the protein-protein interaction. The involvement of lipid raft microdomains
      on the activity of PMCA4b and nNOS was also investigated. Unlike other PMCA
      isoforms, PMCA4 was relatively more concentrated in the raft fractions.
      Disruption of lipid rafts altered the intracellular localization of PMCA4b and
      affected the interaction between PMCA4b and nNOS, which suggest that the unique
      lipid raft distribution of PMCA4 may be responsible for its regulation of nNOS
      activity. In summary, lipid rafts may act as platforms for the PMCA4b regulation
      of nNOS activity and the transient tethering of nNOS to PMCA4b is responsible for
      rapid nNOS deactivation.

PMID- 23549615
TI  - Structural insight into enhanced calcium indicator GCaMP3 and GCaMPJ to promote
      further improvement.
AB  - Genetically encoded Ca(2+) indicators (GECI) are important for the measurement of
      Ca(2+) in vivo. GCaMP2, a widely-used GECI, has recently been iteratively
      improved. Among the improved variants, GCaMP3 exhibits significantly better
      fluorescent intensity. In this study, we developed a new GECI called GCaMPJ and
      determined the crystal structures of GCaMP3 and GCaMPJ. GCaMPJ has a 1.5-fold
      increase in fluorescence and 1.3-fold increase in calcium affinity over GCaMP3.
      Upon Ca(2+) binding, GCaMP3 exhibits both monomeric and dimeric forms. The
      structural superposition of these two forms reveals the role of Arg-376 in
      improving monomer performance. However, GCaMPJ seldom forms dimers under
      conditions similar to GCaMP3. St ructural and mutagenesis studies on Tyr-380
      confirmed its importance in blocking the cpEGFP beta-barrel holes. Our study
      proposes an efficient tool for mapping Ca(2+) signals in intact organs to
      facilitate the further improvement of GCaMP sensors.

PMID- 23549616
TI  - Upregulation of SIRT1 by 17beta-estradiol depends on ubiquitin-proteasome
      degradation of PPAR-gamma mediated by NEDD4-1.
AB  - 17beta-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and
      a down-regulation of PPARgamma. The decrease in PPARgamma expression is mediated
      by increased degradation of PPARgamma. Here we report that PPARgamma is
      ubiquitinated by HECT E3 ubiquitin ligase NEDD4-1 and degraded, along with
      PPARgamma, in response to E2 stimulation. The PPARgamma interacts with ubiquitin
      ligase NEDD4-1 through a conserved PPXY-WW binding motif. The WW3 domain in NEDD4
      1 is critical for binding to PPARGamma. NEDD4-1 overexpression leads to PPARgamma
      ubiquitination and reduced expression of PPARgamma. Conversely, knockdown of
      NEDD4-1 by specific siRNAs abolishes PPARGamma ubiquitination. These data
      indicate that NEDD4-1 is the E3 ubiquitin ligase responsible for PPARgamma
      ubiquitination. Here, we show that NEDD4-1 delays cellular senescence by
      degrading PPARGamma expression. Taken together, our data show that E2 could
      upregulate SIRT1 expression via promoting the PPARGamma ubiquitination-proteasome
      degradation pathway to delay the process of cell senescence.

PMID- 23549617
TI  - Fecal Bacteriotherapy for Recurrent Clostridium difficile Infection: What's Old
      Is New Again?
AB  - In recent years, effective management of recurrent Clostridium difficile
      infection (CDI) has emerged as an important issue for those clinicians who treat
      patients with CDI. In addition to antibiotic-based therapies, including
      alternating use, chaser, and tapering protocols, interest has increased in the
      potential utility of a variety of nonantibiotic forms of adjunctive therapy.
      Among these alternative forms of treatment, the concept of transferring extracts
      of a stool from donors to patients with CDI has been met with great interest
      among researchers, clinicians, and patients alike. Fecal bacteriotherapy, or so
      called fecal microbiota transplantation, for therapy of CDI is a procedure that
      dates back to the 1950s. Recently, however, a variety of studies have garnered
      attention in the lay press, in addition to the standard scientific-reporting
      community. Although no well-controlled trials have been published as yet and the
      details of the procedures used have varied widely between institutions, the
      available evidence suggests that for selected patients, fecal bacteriotherapy
      appears to be generally safe and effective. Concerns about true efficacy and the
      theoretical potential for infectious complications have prevented widespread
      adoption of this concept as standard therapy, but its use in academic and
      community practices is on the rise.

PMID- 23549619
TI  - Experimental visualization of the Bi-O covalency in ferroelectric bismuth ferrite
      (BiFeO3) by synchrotron X-ray powder diffraction analysis.
AB  - The experimental electron-density distribution of ferroelectric bismuth ferrite
      (BiFeO3) has been visualized using the synchrotron X-ray powder diffraction data
      and the maximum-entropy method. The present work has clearly revealed the partial
      covalency of the Bi-O bond, which is a key to understand the spontaneous
      polarization. Density functional theory (DFT) calculation has supported the
      validity of the experimental results.

PMID- 23549618
TI  - The impact of viral infections in children with community-acquired pneumonia.
AB  - For many years viral causes of community-acquired pneumonia were often been given
      limited attention. The number of published studies on influenza alone increased
      fivefold from 2001 to 2010. Specifically several studies have underlined that the
      involvement of viruses in community-acquired pneumonia has been underestimated,
      and this underestimation has been attributed to a lack of appropriate diagnostic
      methods. Now, with the advent of modern molecular assays, it is well recognized
      that viruses account for the largest proportion of community-acquired pneumonia
      in preschool children in both developed and developing countries. Respiratory
      syncytial virus, influenza virus, adenovirus, and parainfluenza virus are the
      major pathogens involved, but the relative importance of additional viruses
      (rhinoviruses, bocavirus, human metapneumovirus) is increasing and will be better
      defined by future research.

PMID- 23549620
TI  - Application of business model innovation to enhance value in health care
      delivery.

PMID- 23549622
TI  - Retractions: Crop improvement through modification of the plant's own genome.

PMID- 23549621
TI  - One-pot catalysis of dehydrogenation of cyclohexanones to phenols and oxidative
      Heck coupling: expedient synthesis of coumarins.
AB  - One-pot reactions leading to highly functionalized coumarins have been developed
      via a Pd(II)-catalyzed dehydrogenation-oxidative Heck-cyclization process.

PMID- 23549624
TI  - [Is regression of cirrhosis in patients with hepatitis B infection possible?
      Regression of cirrhosis due to discontinuation of the inflammatory stimulus].

PMID- 23549625
TI  - [Level of information of students at the University of Regensburg concerning
      organ donation and transplantation--informed or not informed consent in organ
      donation?].
AB  - BACKGROUND: As a result of the actual amendment of the German transplantation
      law, every citizen will be regularly asked by health insurance companies about
      his attitude towards post-mortem organ donation--without the obligation to
      decide. The aim is to increase the willingness of donations as well as the
      availability of organs. Therefore, we investigated the level of information of
      students at the University of Regensburg and their agreement to organ
      transplantation regarding an informed consent. METHODS: Using an
      interdisciplinary developed questionnaire (Medicine, Theology, Educational
      Science) the level of information concerning process and possibilities of organ
      donation, the possession of an organ donor card, as well as the active or passive
      consent to donate organs was investigated. RESULTS: Out of 1225 respondents 31.5%
      had an organ donor card, 49.1% wanted to donate organs, 32.1% were unsure. 98%
      generally favoured organ donation. However, serious information deficits about
      brain death were identified: 37.4% did not know that brain death is a
      prerequisite for a post-mortem organ donation, 18% thought brain death is
      reversible, 52.7% were not aware of the necessity of intensive medical care.
      Furthermore, providing information about other potential donor organs including
      lungs, pancreas, small intestine, and tissue is required. CONCLUSION: Health
      insurance companies and responsible authorities need to close the identified gaps
      in knowledge in order to achieve "informed" consent with organ donation, which
      might increase the availability and number of donor organs.

PMID- 23549626
TI  - [49-year-old woman after kyphoplasty].

PMID- 23549628
TI  - [Treatment of the acute deep vein thrombosis].

PMID- 23549627
TI  - [Severe encephalopathy after taking a "phytopharmacon" from Vietnam].
AB  - HISTORY: A 59-year-old woman went into coma after she had taken a phytopharmacon
      from Vietnamese generally used as an antidiabetic drug to treat her skin disease.
      INVESTIGATIONS: CT-scans revealed signs of pneumonia and cerebral edema. Severe
      brain damage was diagnosed by MRI-investigation. By chemical-toxicological
      analysis of the drug glibenclamide was identified in a concentration of 1.1 mg/g.
      DIAGNOSIS, TREATMENT AND COURSE: The patient developed severe irreversible
      encephalopathy. By neurorehabilitative treatment her physical status slightly
      improved, but she died after 13 months without regaining consciousness.
      CONCLUSIONS: The cause of losing consciousness remained unclear, however, severe
      hypoglycaemia following the use of the drug may be taken into account. An urgent
      warning against the use of such preparations is highly recommended.

PMID- 23549629
TI  - [Treatment of liver metastases of colorectal carcinoma: overview of hyperthermal
      ablation methods].
AB  - AIM AND METHOD: This paper presents the basic techniques and clinical results of
      the most common hyperthermal ablation methods for patients with malignant liver
      metastases of colorectal carcinoma. An overview of recently published data is
      provided using selected articles from the literature and our own clinical
      experience in an interdisciplinary liver centre. RESULTS: Radiofrequency ablation
      (RFA), microwave ablation (MWA) and laser ablation (LITT) show comparable results
      concerning survival data. Local recurrence is less frequent after LITT (7,1-10%)
      than after RFA (32-44%) and MWA (7-15%). Survival depends on many factors. The 3
      year survival rate for RFA ranges from 20,2-71,3%, for MWA it is 51,1% and for
      LITT from 56-77%. Mean complication rates range from 1,8-10%. Recent studies
      showed promising results after combined therapy of regional chemotherapy or
      regional radiotherapy with thermal ablation. CONCLUSION: Ablation methods such as
      RFA, MWA and LITT show good local tumor control with low complication rates and
      are usually performed on an outpatient basis. Indications are <5 metastases
      limited to the liver with a maximum diameter of <=4 cm when surgical resection is
      contraindicated or has been previously performed. The decision should be made by
      an interdisciplinary tumor board.

PMID- 23549630
TI  - [New strategies in cardioprotection during acute myocardial infarction: Impact of
      hypoxic nitrate-nitrite-NO signaling].
AB  - Acute myocardial infarction remains one of the leading causes of morbidity,
      mortality and disability in industrialized countries. After an acute myocardial
      infarction, early and successful myocardial reperfusion is the most effective
      strategy for reducing the size of a myocardial infarct and improving the clinical
      outcome. The process of restoring blood flow to the ischemic myocardium, however,
      can induce injury itself. This phenomenon, termed myocardial ischemia reperfusion
      injury (IRS), can paradoxically reduce the beneficial effects of myocardial
      reperfusion. In experimental studies a number of strategies have been shown to
      ameliorate lethal reperfusion injury. However, the translation of these
      beneficial effects into the clinical setting has been disappointing. Modulation
      of the hypoxic nitrate-nitrite-nitric oxide (NO) pathway may have the potential
      to challenge this problem. First translational studies are promising and clinical
      trials are ongoing.

PMID- 23549632
TI  - Facial onset sensory motor neuronopathy: not always a slowly progressive
      disorder.

PMID- 23549631
TI  - Unresponsive thrombotic thrombocytopenic purpura in critically ill adults.
AB  - INTRODUCTION: The prognosis of thrombotic thrombocytopenic purpura (TTP) has
      considerably improved since the introduction of plasma exchange (PEX) therapy.
      However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries
      high morbidity and mortality rates, indicating a need for early specific
      treatments. PATIENTS AND METHODS: In a retrospective study including consecutive
      adults with TTP admitted between January 1997 and January 2011 in a teaching
      hospital intensive care unit (ICU), our objective here is to identify early
      clinical and laboratory features predicting Un-TTP. Patients who responded to
      plasma exchange and steroids (N = 49) were compared with patients with
      unresponsive TTP defined as requirement for other treatments, protracted course,
      or death (N = 37, 43 %). RESULTS: Hospital mortality was 24.3 % in the Un-TTP
      group. Variables associated with Un-TTP on univariate logistic regression were
      older age, cardiac involvement, neurological involvement, higher anti-a
      disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13)
      immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher
      Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for
      higher plasma volumes to obtain remission, and greater use of adjuvant treatments
      and life-sustaining interventions. Multivariate logistic regression identified
      four factors independently associated with Un-TTP: age over 60 years [odds ratio
      (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 %
      CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at
      diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30
      11.62). CONCLUSION: Therapeutic intensification starting on day 3 or even earlier
      in patients with the independent risk factors for unresponsive TTP identified in
      our study deserves evaluation in a multicenter prospective study.

PMID- 23549633
TI  - A common gene variant in PLS3 predicts colon cancer recurrence in women.
AB  - Recent evidence suggests that PLS3 (T-Plastin), an important member of the actin
      filamentous network, significantly influences cell invasion and metastasis.
      Germline polymorphisms within the PLS3 gene may impact the gene's function,
      resulting in inter-individual differences in tumor recurrence capacity. In the
      present study, we investigated the association of germline polymorphisms in PLS3
      to predict time to recurrence (TTR) in patients with stage II and III colon
      cancer. A total of 264 patients with histologically confirmed colon cancer were
      included in this retrospective study. Germline DNA was genotyped for rs871773
      C>T, rs757124 C>G, rs1557770 G>T, rs6643869 G>A, and rs2522188 C>T in the PLS3
      gene by 5'-exonuclease (TaqManTM) technology. As the PLS3 gene is located on the
      X chromosome, a gender-specific statistical analysis was performed. In univariate
      analysis, the minor allele of PLS3 rs871773 C>T was significantly associated with
      decreased TTR in women (hazard ratio (HR) = 5.02; 95 % confidence interval (CI) =
      1.251-20.114; p = 0.023) and remained significantly associated in multivariate
      analysis (HR = 6.165; 95 % CI = 1.538-24.716; p = 0.010). Female patients
      carrying the C/T genotype in PLS3 rs871773 showed a median TTR of 69 months. In
      contrast, female patients with homozygous C/C had a median TTR of 112 months.
      There were no significant associations between PLS3 rs871773 C>T and TTR in male
      and between the other polymorphisms and TTR in male or female colon cancer
      patients. In conclusion, we identified a common gene variant in PLS3 as an
      independent prognostic marker in female patients with stage II and III colon
      cancer. Larger prospective trials are warranted to confirm these findings.

PMID- 23549635
TI  - Tailoring the catalytic activity of electrodes with monolayer amounts of foreign
      metals.
AB  - During the past decade, electrocatalysis has attracted significant attention
      primarily due to the increased interest in the development of new generations of
      devices for electrochemical energy conversion. This has resulted in a progress in
      both fundamental understanding of the complex electrocatalytic systems and in the
      development of efficient synthetic schemes to tailor the surface precisely at the
      atomic level. One of the viable concepts in electrocatalysis is to optimise the
      activity through the direct engineering of the properties of the topmost layers
      of the surface, where the reactions take place, with monolayer and sub-monolayer
      amounts of metals. This forms (bi)metallic systems where the electronic structure
      of the active sites is optimised using the interplay between the nature and
      position of the atoms of solute metals at the surface. In this review, we focus
      on recent theoretical and experimental achievements in designing efficient
      (bi)metallic electrocatalysts with selective positioning of foreign atoms to form
      a variety of active catalytic sites at the electrode surface. We summarize recent
      results published in the literature and outline challenges for computational and
      experimental electrocatalysis to engineer active and selective catalysts using
      atomic layers.

PMID- 23549634
TI  - Management of patients in a combined thyroid eye clinic in secondary care.
AB  - The European Group on Graves' Orbitopathy (EUGOGO) recommends the use of
      specialised multidisciplinary clinics for the management of thyroid eye disease
      (TED). In the UK, many patients with TED are managed outside of specialised
      clinics. We describe the organisation of a combined TED clinic in a secondary
      care setting and present the result of a prospective audit of the patient
      characteristics and outcomes during the first four years of a combined TED
      clinic. Of a total of 132 patients referred to the TED clinic, 114 (86 %) had TED
      (90 females, median age 56 years; range 17-90 years). At presentation, 77 (67 %)
      were current or ex-smokers and 99 (87 %) were biochemically euthyroid. Median
      duration of eye symptoms was 12 months. Fifty-two percent, 45 and 3 had mild,
      moderate-to-severe and sight-threatening TED, respectively. Only 18 % of patients
      had a clinical activity score (CAS) of >=3. Sixty-nine patients (61 %) required
      follow-up appointments in the TED clinic. In those who required follow-up, 43 %
      (n = 30) received either immunosuppressive or surgical treatment. CAS improved
      from first to final visit, with 29 % (n = 20) having a CAS of >=3 at the first
      visit and 1 % (n = 1) at the final visit (p = 0.0001). There was also a decrease
      in prevalence of smoking and thyroid dysfunction at the final visit. A
      multidisciplinary specialised TED clinic offers an optimal setting for managing
      patients with TED; however, patients are often referred late to a specialist TED
      clinic. 

PMID- 23549636
TI  - Microscopic effects of the bonding configuration of nitrogen-doped graphene on
      its reactivity toward hydrogen peroxide reduction reaction.
AB  - We report a density functional theory (DFT) study of microscopic detailed effects
      of the bonding configuration of nitrogen-doped graphene (N-graphene) within the
      carbon lattice (including pyridinic, pyrrolic, and graphitic N) on the reactivity
      and mechanistic processes of H2O2 reduction reaction. We simulated the adsorption
      process of H2O2, analyzed the mechanistic processes, and calculated the
      reversible potential of each reaction step of the H2O2 reduction reaction on N
      graphene. The results indicate that the adsorption of H2O2 on the pristine and N
      doped graphene surfaces occurs via physisorption without the formation of a
      chemical bond. When H(+) is introduced into the system, a series of reactions can
      occur, including the breakage of the O-O bond, the formation of an O-C chemical
      bond between oxygen and graphene, and the creation of water molecules. The
      results also indicate a decrease in the energy of the system and a positive
      reversible potential for each reaction step. The calculations of the relative
      energy of each reaction step and the value of the onset potential for H2O2
      reduction reaction suggest that the reactivity of pristine and N-doped graphene
      has the following order: pyridinic N-graphene > pyrrolic N-graphene > graphitic N
      graphene > pristine graphene. We also proposed an explanation based on
      electrostatic potential calculations for this dependence of the reactivity order
      on the bond configuration of the doping in N-graphene. The results of this study
      should help in the atomic-scale understanding of the dependence of the reactivity
      of N-graphene on its microstructure, inspire the study of various types of
      heteroatom-doped graphenes to improve their catalytic efficiency, and provide a
      theoretical framework to analyze their reactivities.

PMID- 23549637
TI  - Multi-institutional profile of adults admitted to pediatric intensive care units.
AB  - IMPORTANCE: Growing numbers of persons with childhood-onset chronic illnesses are
      surviving to adulthood. Many use pediatric hospitals for their inpatient needs.
      To our knowledge, the prevalence and characteristics of adult pediatric intensive
      care unit patients have not been reported. OBJECTIVES: To estimate the proportion
      of adults admitted to pediatric intensive care units (PICUs), characterize them,
      and compare them with older adolescents. DESIGN: One-year cross-sectional
      analysis. SETTING: Pediatric intensive care units in the United States that
      participated in the Virtual Pediatric Intensive Care Unit Systems. PARTICIPANTS:
      Pediatric intensive care unit patients 15 years or older admitted in 2008. MAIN
      OUTCOME MEASURES: We compared adults with adolescents across clinical
      characteristics and outcomes. Mixed-effects logistic regression was used to
      estimate the independent association of age with PICU mortality. RESULTS: Seventy
      PICUs had 67 629 admissions; 1954 admissions (2.7%) were patients 19 years or
      older; and 9105 admissions (13.5%) were patients aged 15 to 18 years. The
      proportion of adults (>=19 years) varied considerably by PICU (range, 0%-9.2%).
      As age increased, the proportion of patients who had a complex chronic condition
      and planned or perioperative admissions increased; the proportion of trauma
      related admissions decreased. Patients aged 21 to 29 years had a 2 times (95% CI,
      1.3-3.2; P = .004) greater odds of PICU mortality compared with adolescent
      patients, after adjusting for Paediatric Index of Mortality score, sex, trauma,
      and having a complex chronic condition. Being 30 years or older was associated
      with a 3.5 (95% CI, 1.3-9.7; P = .01) greater odds of mortality. CONCLUSIONS AND
      RELEVANCE: In this multi-institutional study, adults constituted a small but high
      risk proportion of patients in some PICUs, suggesting that these PICUs should
      have plans and protocols specifically focused on this group.

PMID- 23549638
TI  - Efficacy and safety of laparoscopic splenectomy in thrombocytopenia secondary to
      systemic lupus erythematosus.
AB  - This study aims to investigate the efficacy and safety of laparoscopic
      splenectomy (LS) in the management of refractory thrombocytopenia associated with
      systemic lupus erythematosus (SLE). From January 2003 to February 2012, 20
      patients underwent splenectomy for thrombocytopenia associated with SLE. Of
      these, 11 underwent open (SLE-OS group) and 9 underwent laparoscopic splenectomy
      (SLE-LS group). Another 15 patients with ITP underwent LS (ITP-LS group) were
      categorized as the control group. Surgical indications, perioperative details,
      and short- (90 days) and long- (median, 42 months) term hematological outcomes
      were assessed. Splenectomy was successful in all 20 SLE patients. The mean
      platelet count increased from 23 * 10(9)/L before splenectomy to 289.2 * 10(9)/L
      and 144.2 * 10(9)/L after 3 and 6 months, respectively, and was 115.5 * 10(9)/L
      at the last visit, with a 3-month complete response (CR) rate of 100 %. After a
      median follow-up of 42 months, 17 patients (85 %) had a CR or partial response
      (PR) to splenectomy plus medical therapy. SLEDAI score and dosage of steroids
      decreased significantly after splenectomy. None of these patients experienced any
      postoperative infection, bleeding, or thrombotic events. SLE-LS group had lower
      volumes of estimated blood loss and postoperative drainage and shorter
      postoperative hospital stay than SLE-OS group. There were no statistically
      significant differences between the SLE-LS and ITP-LS groups in operation time,
      estimated blood loss, and postoperative hospital stay. Splenectomy is effective
      and safe in the management of refractory thrombocytopenia secondary to SLE. LS
      may be safe and effective in thrombocytopenia associated with SLE.

PMID- 23549639
TI  - Risk factors for body composition abnormalities in systemic sclerosis.
AB  - The aim of this study was to evaluate the body composition (BC), bone mineral
      density (BMD), and the food intake in women with systemic sclerosis (SSc)
      compared to a control group, in order to identify main risk factors for BC
      abnormalities in SSc. Sixty-one SSc women and 67 age- and gender-matched controls
      were included. Spine, femur, and total body BMD measurements were performed using
      dual-energy X-ray absorptiometry. BC measurements included total lean (LM), fat
      mass (FM), and relative skeletal muscle mass index (RSMI) assessment. The food
      intake was calculated from 3-day food records and transformed into energy and
      nutrients. The 61 SSc patients [30 with diffuse cutaneous disease (dcSSc) and 31
      with limited cutaneous SSc (lcSSc)] had significantly lower body mass index
      (BMI), LM, and FM, as well as lower BMD values compared to controls. Besides, the
      group with dcSSc, but not those with lcSSc, showed significantly lower BC and BMD
      measurements than controls. There was a significant inverse correlation between
      disease duration and BMI, LM, and RSMI. The total energy, macronutrients, and
      essential amino acids intakes were similar between patients and controls. After
      multivariate analysis, longer disease duration was the only risk factor
      associated with sarcopenia (RSMI below 5.45 kg/m(2); OR = 1.36, 95% CI 1.07-1.7).
      The present study showed an abnormal BC and a lower BMD, especially in dcSSc
      women, regardless of current food intake. Longer disease duration was associated
      with a higher risk of sarcopenia in SSc patients.

PMID- 23549640
TI  - Autonomic dysfunction in psoriatic arthritis.
AB  - Autonomic nervous system (ANS) involvement has been studied in systemic lupus
      erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, and
      ankylosing spondylitis but still has not been studied in psoriatic arthritis
      (PsA). The aim of this study was to investigate the prevalence and the nature of
      autonomic neuropathy in patients with PsA. Sixteen patients of PsA and 15 age and
      sex matched control subjects were studied prospectively using a battery of
      noninvasive tests. Cardiovascular autonomic neuropathy (CAN) was diagnosed by
      applying four cardiovascular reflex tests, and peripheral sympathetic autonomic
      function was assessed by Sudoscan. Patients with PsA had significantly higher
      heart rate response to standing (p = 0.01), blood pressure response to standing
      (p = 0.02), and Sudoscan (p = 0.01) when compared with healthy controls. Fifty
      percent (n = 8) of the patients with PsA had at least two or more abnormal CAN
      parasympathetic dysfunction; of these, 18.75% (n = 3) of the patients had
      abnormal parasympathetic and sympathetic dysfunction, 68.7% (n = 11) and 25% (n =
      4) of the patients had at least one abnormal parasympathetic and sympathetic
      parameters, respectively, and 37.5% (n = 6) of the patients had moderate
      sudomotor dysfunction. About 18.7% (n = 3) of our parasympathetic dysfunction
      patients had autonomic symptoms. None of healthy volunteers had abnormal ANS
      dysfunction. Heart rate response significantly correlated with erythrocyte
      sedimentation rate (p < 0.05) and C-reactive protein (p < 0.05) levels. In
      conclusion, cardiovascular autonomic and peripheral sympathetic neuropathy occurs
      in PsA. Parasympathetic function is more commonly found to be abnormal than
      sympathetic function. There is no correlation of peripheral sympathetic
      dysfunction with cardiovascular autonomic neuropathy.

PMID- 23549641
TI  - A three-dimensional assembly of pyrene dye on a tetraphenylethane scaffold
      enhances fluorescence quantum yield.
AB  - A three-dimensional pyrene assembly on a tetraphenylethane skeleton enhanced the
      fluorescence quantum yield compared to the yield obtained when using monomeric
      species, without changing the shape of the emission spectrum. The unique spacing
      of the pyrene units may prevent intramolecular fluorescence quenching or non
      radiative decay.

PMID- 23549642
TI  - Microwave-assisted preparation of monolithic molecularly imprinted polymeric
      fibers for solid phase microextraction.
AB  - In this work, a novel microwave-assisted method was developed for fast and batch
      fabrication of monolithic molecularly imprinted polymer (MIP) fibers. It was
      based on in situ polymerization in a flexible capillary mold under microwave
      irradiation. The proposed method greatly shortened the preparation time (about 20
      fold) in comparison with the conventional heating. The model template, bisphenol
      A (BPA) imprinted MIP fiber, was prepared and used for solid phase
      microextraction (SPME) prior to high performance liquid chromatography (HPLC)
      determination of BPA and its analogues, i.e., diethylstilbestrol (DES) and
      hexestrol (HEX). Under the established optimum conditions, the limits of
      detection for BPA, DES and HEX were 2.0 ng mL(-1), 5.1 ng mL(-1), and 3.3 ng mL(
      1), respectively. The fiber-to-fiber extraction (n = 5) was reproducible with the
      relative standard deviation in the range of 6.6-9.5%. The MIP fiber was used for
      selective extraction of BPA, DES and HEX in tap water, sewage and urine samples,
      and the relative recoveries for MIP-SPME-HPLC analysis of BPA, DES and HEX ranged
      from 82.5% to 103.8%. The advantages provided by this microwave-assisted method
      will make it a useful tool for preparation of MIP fibers with good SPME
      performance.

PMID- 23549643
TI  - Fractional flow reserve assessment of left main stenosis in the presence of
      downstream coronary stenoses.
AB  - BACKGROUND: Several studies have shown that fractional flow reserve (FFR)
      measurement can aid in the assessment of left main coronary stenosis. However,
      the impact of downstream epicardial stenosis on left main FFR assessment with the
      pressure wire in the nonstenosed downstream vessel remains unknown. METHODS AND
      RESULTS: Variable stenoses were created in the left main coronary arteries and
      downstream epicardial vessels in 6 anaesthetized male sheep using balloon
      catheters. A total of 220 pairs of FFR assessments of the left main stenosis were
      obtained, before and after creation of a stenosis in a downstream epicardial
      vessel, by having a pressure-sensor wire in the other nonstenosed downstream
      vessel. The apparent left main FFR in the presence of downstream stenosis
      (FFR(app)) was significantly higher compared with the true FFR in the absence of
      downstream stenosis (FFR(true); 0.80+/-0.05 versus 0.76+/-0.05; estimate of the
      mean difference, 0.035; P<0.001). The difference between FFR(true) and FFR(app)
      correlated with composite FFR of the left main plus stenosed artery (r=-0.31;
      P<0.001) indicating that this difference was greater with increasing epicardial
      stenosis severity. Among measurements with FFR(app) >0.80, 9% were associated
      with an FFR(true) of <0.75. In all instances, the epicardial lesion was in the
      proximal portion of the stenosed vessel, and the epicardial FFR (combined FFR of
      the left main and downstream stenosed vessel) was <=0.50. CONCLUSIONS: A
      clinically relevant effect on the FFR assessment of left main disease with the
      pressure wire in a nonstenosed downstream vessel occurs only when the stenosis in
      the other vessel is proximal and very severe.

PMID- 23549644
TI  - Stroke after primary percutaneous coronary intervention in patients with ST
      segment elevation myocardial infarction: timing, characteristics, and clinical
      outcomes.
AB  - BACKGROUND: Stroke is a rare but potentially devastating complication of acute
      myocardial infarction. Little is known about stroke timing, characteristics, and
      clinical outcomes in patients with ST-segment elevation myocardial infarction
      treated with primary percutaneous coronary intervention (PCI). METHODS AND
      RESULTS: We studied 5372 patients enrolled in the Assessment of Pexelizumab in
      Acute Myocardial Infarction (APEX-AMI) trial. We analyzed stroke incidence, type,
      timing, and association with the prespecified 90-day clinical outcomes. Cox
      proportional hazards modeling was performed to assess the relationship between
      stroke and outcomes, after adjusting baseline characteristics and analyzing
      stroke as a time-dependent covariate. Stroke occurred in 69 primary patients with
      PCI (1.3%). A third of strokes were ischemic (n=23; 33%), 12% (n=8) were
      hemorrhagic, and the remaining 55% (n=38) were of uncertain type. The median
      (25th, 75th percentile) time of stroke occurrence was 6 (3, 14) days. Overall,
      43% of strokes occurred within 48 hours of PCI, and all hemorrhagic strokes
      occurred within 48 hours. Stroke was associated with an increased risk of 90-day
      death (unadjusted hazard ratio [HR], 8.0; 95% confidence interval [CI], 4.8
      13.5), congestive heart failure (unadjusted HR, 3.2; 95% CI, 1.3-7.8), and 30-day
      hospital readmission (unadjusted HR, 3.2; 95% CI, 2.0-5.1). After adjustment,
      stroke was still strongly associated with 90-day death (adjusted HR, 5.6; 95% CI,
      3.2-9.8) and the combination end point of death, congestive heart failure, or
      cardiogenic shock at 90 days (adjusted HR, 2.4; 95% CI, 1.2-4.7). CONCLUSIONS:
      Stroke is an infrequent complication in the setting of ST-segment elevation
      myocardial infarction treated with primary PCI but is associated with increased
      morbidity and mortality. Studies to determine mechanisms that may be responsible
      for strokes that occur >48 hours from primary PCI are warranted. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00091637.

PMID- 23549645
TI  - Evaluation of advanced Lukas-Kanade optical flow on thoracic 4D-CT.
AB  - Extensive use of high frequency imaging in medical applications permit the
      estimation of velocity fields which corresponds to motion of landmarks in the
      imaging field. The focus of this work is on the development of a robust local
      optical flow algorithm for velocity field estimation in medical applications.
      Local polynomial fits to the medical image intensity-maps are used to generate
      convolution operators to estimate the spatial gradients. A novel polynomial
      window function with a compact support is used to differentially weight the
      optical flow gradient constraints in the region of interest. Tikhonov
      regularization is exploited to synthesize a well posed optimization problem and
      to penalize large displacements. The proposed algorithm is tested and validated
      on benchmark datasets for deformable image registration. The ten datasets include
      large and small deformations, and illustrate that the proposed algorithm
      outperforms or is competitive with other algorithms tested on this dataset, when
      using mean and variance of the displacement error as performance metrics. 

PMID- 23549646
TI  - New concept using Passive Infrared (PIR) technology for a contactless detection
      of breathing movement: a pilot study involving a cohort of 169 adult patients.
AB  - A pilot study has been conducted to validate the Breath Motion Detecting System
      (BMDS), a new concept using Passive Infrared (PIR) technology for a contactless
      detection of respiratory movements. The primary objective of the study was to
      show if movements detected during sleep by the BMDS were indeed related to
      breathing. This medical device is not intended to measure the respiratory rate,
      but in a second step, it will be able to detect pathological central apnea in
      adults. One hundred and sixty-nine adult patients underwent a full
      polysomnography in which each respiratory movement was recorded concomitantly
      through the BMDS. Curves obtained by the BMDS were compared to those of thoracic
      movements recorded by classical piezoelectric belts and of pressure obtained with
      nasal cannula. The correlations between the PIR sensors were highly indicative of
      respiratory movement detection. Since PIR sensors are sensitive only to the
      exemplification of the rib cage, they did not detect obstructive apnea.
      Unfortunately, only a few patients in the studied population had a central apnea.
      Moreover as our sleep laboratory was equipped only with piezoelectric bands, the
      central apnea respiratory effort data are not a validated signal to be used
      during sleep recordings. The data recorded by the BMDS demonstrate the ability of
      the PIR technology to detect respiratory movements in adults. The concept is
      practical, inexpensive and safe for the patient. Further studies with respiratory
      inductive plethysmography are needed to investigate the potential of BMDS to
      detect central apneas. 

PMID- 23549647
TI  - Developing therapeutic antibodies for neurodegenerative disease.
AB  - The central nervous system has been considered off-limits to antibody
      therapeutics. However, recent advances in preclinical and clinical drug
      development suggest that antibodies can cross the blood-brain barrier in limited
      quantities and act centrally to mediate their effects. In particular,
      immunotherapy for Alzheimer's disease has shown that targeting beta amyloid with
      antibodies can reduce pathology in both mouse models and the human brain, with
      strong evidence supporting a central mechanism of action. These findings have
      fueled substantial efforts to raise antibodies against other central nervous
      system targets, particularly neurodegenerative targets, such as tau, beta
      secretase, and alpha-synuclein. Nevertheless, it is also apparent that antibody
      penetration across the blood-brain barrier is limited, with an estimated 0.1-0.2
      % of circulating antibodies found in brain at steady-state concentrations. Thus,
      technologies designed to improve antibody uptake in brain are receiving increased
      attention and are likely going to represent the future of antibody therapy for
      neurologic diseases, if proven safe and effective. Herein we review briefly the
      progress and limitations of traditional antibody drug development for
      neurodegenerative diseases, with a focus on passive immunotherapy. We also take a
      more in-depth look at new technologies for improved delivery of antibodies to the
      brain.

PMID- 23549648
TI  - Neuromuscular and systemic presentations in adults: diagnoses beyond MERRF and
      MELAS.
AB  - Mitochondrial diseases are a diverse group of inherited and acquired disorders
      that result in inadequate energy production. They can be caused by inheritable
      genetic mutations, acquired somatic mutations, and exposure to toxins (including
      some prescription medications). Normal mitochondrial physiology is responsible,
      in part, for the aging process itself, as free radical production within the
      mitochondria results in a lifetime burden of oxidative damage to DNA, especially
      the mitochondrial DNA that, in turn, replicate the mutational burden in future
      copies of itself, and lipid membranes. Primary mitochondrial diseases are those
      caused by mutations in genes that encode for mitochondrial structural and
      enzymatic proteins, and those proteins required for mitochondrial assembly and
      maintenance. A number of common adult maladies are associated with defective
      mitochondrial energy production and function, including diabetes, obesity,
      hyperthyroidism, hypothyroidism, and hyperlipidemia. Mitochondrial dysfunction
      has been demonstrated in many neurodegenerative disorders, including Alzheimer's
      disease, Parkinson disease, amyotrophic lateral sclerosis, and some cancers.
      Polymorphisms in mitochondrial DNA have been linked to disease susceptibility,
      including death from sepsis and survival after head injury. There is considerable
      overlap in symptoms caused by primary mitochondrial diseases and those illnesses
      that affect mitochondrial function, but are not caused by primary mutations, as
      well as disorders that mimic mitochondrial diseases, but are caused by other
      identified mutations. Evaluation of these disorders is complex, expensive, and
      not without false-negative and false-positive results that can mislead the
      physician. Most of the common heritable mitochondrial disorders have been well
      described in the literature, but can be overlooked by many clinicians if they are
      uneducated about these disorders. In general, the evaluation of the classic
      mitochondrial disorders has become straightforward if the clinician recognized
      the phenotype and orders appropriate confirmatory testing. However, the majority
      of patients referred for a mitochondrial evaluation do not have a clear
      presentation that allows for rapid identification and testing. This article
      provides introductory comments on mitochondrial structure, physiology, and
      genetics, but will focus on the presentation and evaluation of adults with
      mitochondrial symptoms, but who may not have a primary mitochondrial disease.

PMID- 23549650
TI  - Introduction of laparoscopic sacral colpopexy to a fellowship training program.
AB  - INTRODUCTION AND HYPOTHESIS: Minimally invasive sacral colpopexy has increased
      over the past decade, with many senior physicians adopting this new skill set.
      However, skill acquisition at an academic institution in the presence of
      postgraduate learners is not well described. This manuscript outlines the
      introduction of laparoscopic sacral colpopexy to an academic urogynecology
      service that was not performing minimally invasive sacral colpopexies, and it
      also defines a surgical learning curve. METHODS: The first 180 laparoscopic
      sacral colpopexies done by four attending urogynecologists from January 2009 to
      December 2011 were retrospectively analyzed. The primary outcome was operative
      time. Secondary outcomes included conversion to laparotomy, estimated blood loss,
      and intra- and postoperative complications. Linear regression was used to analyze
      trends in operative times. Fisher's exact test compared surgical complications
      and counts of categorical variables. RESULTS: Mean total operative time was 250
      +/- 52 min (range 146-452) with hysterectomy and 222 +/- 45 (range 146-353) for
      sacral colpopexy alone. When compared with the first ten cases performed by each
      surgeon, operative times in subsequent groups decreased significantly, with a 6
      16.3% reduction in overall times. There was no significant difference in the rate
      of overall complications regardless of the number of prior procedures performed
      (p = 0.262). CONCLUSIONS: Introduction of laparoscopic sacral colpopexy in a
      training program is safe and efficient. Reduction in operative time is similar to
      published learning curves in teaching and nonteaching settings. Introducing this
      technique does not add additional surgical risk as these skills are acquired.

PMID- 23549651
TI  - [PALME--Arrival in Reality].
AB  - PALME is an emotion-centred parental training for single mothers and their
      children based on attachment theory. It was designed for the prevention of
      maternal depression and its long-term effects on the mother-child relation and
      the infant's development. Using the example of the PALME programme, inherent and
      external factors are demonstrated which can contribute to the successful transfer
      of prevention programmes into psychosocial care and other practice areas. 

PMID- 23549652
TI  - [Active Health Promotion among the Aged--Transfer of a Programme from an Urban to
      a Rural Area].
AB  - The objective of the programme "active health promotion in old age" is to improve
      physical activity, healthy nutrition and the social integration of older people.
      The intervention has been successfully implemented in an urban setting and was
      then transferred to a rural area. Although the rural area has a major impact on
      recruitment, access, and factors of implementation, results demonstrate that
      overall the intervention was implemented successfully. Moreover, structural
      conditions (e.g., availability of fitness clubs) are essential for a successful
      transfer.

PMID- 23549653
TI  - [Prevention of Type 2 Diabetes: Evidence-Based Patient Information--A Randomised
      Controlled Trial].
AB  - The aim of this study was to compare the effect of our newly developed online
      evidence-based patient information (EBPI) vs. standard patient information about
      subthreshold elevated blood glucose levels and primary prevention of diabetes on
      informed patient decision-making. EBPI significantly improved knowledge about
      elevated glucose levels, but also increased decisional conflict and critical
      attitudes to screening and treatment options. The intention to undergo metabolic
      screening decreased as a result. 

PMID- 23549654
TI  - [Effectively Preventing Eating Disorders with the School-Based Programs "PriMa"
      and "Torera" for Adolescents in the 6th and 7th Grades].
AB  - The aim of this study was to assess the effects of 2 German school-based primary
      prevention programmes for (pre)adolescents, aged 11-13 years, with 9 manual
      guided lessons. 92 (PriMa, n=1,553 girls) and 22 (Torera, n=256 boys, 277 girls)
      Thuringian secondary schools participated in controlled trials with pre-post
      assessment. Girls and students at risk showed significant improvements of
      conspicuous eating behaviour and body self-esteem with small to medium effect
      sizes. Implementation costs were ? 2.50 per student.

PMID- 23549655
TI  - [Recruitment for general practice - relationship between practice-based
      curriculum and career choice].
AB  - BACKGROUND: Demographic change and recruitment problems in general practice are
      increasingly threatening an adequate primary care workforce in many countries.
      Medical schools play an important role in attracting young physicians to this
      field. The influence of the general practice curriculum on the career choice of
      graduates has not yet been sufficiently investigated. METHODS: The present study
      combines continuously collected data of medical students concerning the
      participation in miscellaneous general practice courses with data of a later
      graduate survey. RESULTS: Response rate was 64.2%. Although only 4.7% of the
      participants preferred a career in general practice at study entry, this
      specialty was, at 12.3%, the second most frequent career choice. Among the future
      general practitioners, only 18.5% had initially planned this career. The future
      general practitioners took part significantly more frequently in all facultative
      general practice courses. They reported more frequently to have met role models
      in general practice and to have gained experience in rural areas. Future general
      practitioners would more often prefer to work in rural areas in the future.
      CONCLUSIONS: Overall, the present results indicate that a broad and practice
      oriented general practice curriculum has the potential to attract medical
      students to the specialty.

PMID- 23549656
TI  - Establishment of prevention: what do dentists in northern Germany suggest?
AB  - OBJECTIVE: Dentists' suggestions for the establishment of preventive care were
      investigated on 3 levels; dentist, dental associations and unions (DAU), and
      health care system (HCS). Associations between categories of suggestions and
      dentists' characteristics were explored. METHODS: A postal survey was sent to
      2,075 dentists practicing in Bremen and Lower Saxony. The answers on 3 open-ended
      questions were analysed in a qualitative manner based on the quality control
      protocol (QCP) of the Federal Joint Committee. Quantitative methods were used for
      exploring associations between categories of suggestions and gender as well as
      age. RESULTS: Response rate was 33% (n=685). Dentists made 2,120 suggestions
      (dentist=752, DAU= 574, HCS= 794). The majority of dentists (90%) suggested
      educating and motivating patients. Dentists stated that support from DAU is
      needed in educating the public (50%), offering preventive-oriented training
      (35%), and in advertising for prophylaxis (18%). On the HCS level, about 60% of
      the suggestions concerned remunerating prophylaxis and expanding the existing
      bonus system. Significantly more female (p=0.010) and younger dentists (p=0.031)
      contributed to educating patients than male and older dentists. CONCLUSION:
      Education is the key message of this work. Essential topics such as prevention
      for elderly and risk groups were not a focal point. Education on the DAU and HCS
      levels can be realised through organising nation-wide health campaigns. Funding
      options for prevention and regulating multidisciplinary work between dentists and
      other health-care providers should be examined. These changes can contribute
      enormously to further establish prevention.

PMID- 23549657
TI  - Three-Color FRET expands the ability to quantify the interactions of several
      proteins involved in actin filament nucleation.
AB  - With traditional 2-color Forster Resonance Energy Transfer (FRET) microscopy,
      valuable quantitative analyses can be conducted. Correlations of donor (D),
      acceptor (A) and their ratios (D:A) with energy transfer efficiency (E%) or
      distance (r) allows measurement of changes between control and experimental
      samples; also, clustered vs. random assembly of cellular components can be
      differentiated. Essentially, only the above three parameters D, A and D:A vs. E%
      are the basis for these deductions. 3-color FRET uses the same basic parameters,
      but exponentially expands the opportunities to quantify interrelationships among
      3 cellular components. We investigated a number of questions based on the results
      of a triple combination (F1-F2-F3) of TFP-NWASP/Venus-IQGAP1/mCherry-Actin - all
      involved in the nucleation of actin - to apply the extensive analysis assay
      possible with 3-color FRET. How do changing N-WASP or IQGAP1 fluorescence levels
      affect actin fluorescence? What is the effect on E% of NWASP-actin by IQGAP1 or
      E% of IQGAP1-actin by N-WASP? These and other questions are explored in the
      context of all proteins of interest being in FRET distance vs. any two in the
      absence of the third. 4 cases are compared based on bleed-through corrected FRET:
      (1) all 3 interact, (2) only F1-F3 and F2-F3 [not F1-F2], (3) only F1-F2 and F2
      F3 interact [not F1-F3], (4) only F1-F2 and F1-F3 interact [not F2-F3]. Other
      than describing the methodology in detail, several biologically relevant results
      are presented showing how E% (i.e. distance), fluorescence levels and ratios are
      affected in each of the cases. These correlations can only be observed in a 3
      fluorophore combination. 3-color FRET will greatly expand the investigative range
      of quantitative analysis for the life-science researcher.

PMID- 23549659
TI  - A rare case of large nasal teratoma associated with congenital heart anomalies in
      a neonate.

PMID- 23549658
TI  - Green-light fundus autofluorescence in diabetic macular edema.
AB  - AIM: To evaluate the role of central green-light fundus autofluorescence (FAF) in
      diabetic macular edema (DME). METHODS: A consecutive series of 92 study eyes with
      diabetic retinopathy were included. Out of those, 51 diabetic eyes had DME and
      were compared to 41 diabetic eyes without DME. In all subjects, green-light FAF
      images were obtained, quantified and classified into various FAF patterns. Cross
      sectional optical coherence tomography (OCT) scans were obtained for evaluation
      of Inner/Outer segment (IS/OS) layer integrity, measurements of central RPE-IS/OS
      layer thickness as well as classification of DME into various subtypes. RESULTS:
      Mean central green-light FAF intensity of eyes with DME (1.289+/-0.140)log did
      not significantly differ from diabetic patients without DME (1.317+/-0.137)log.
      Most classifiable FAF patterns were seen in patients with cystoid DME. Mean
      central retinal thickness (CRT) of all study eyes with DME was (501.9+/-112.4)um
      compared to (328.2+/-27.0)um in diabetic patients without DME. Patients with DME
      had significantly more disrupted photoreceptor IS/OS layers than diabetic
      patients without DME (28/51 vs 5/41, P<0.001). Mean RPE-IS/OS thickness of
      patients with DME (60.7+/-14.1)um was significantly (P<0.001) lower than in
      diabetic eyes without DME (73.5+/-9.4)um. Correlation analys1s revealed non
      significant correlations of green-light FAF intensity and OCT parameters in all
      subtypes of DME. CONCLUSION: Our results indicate a poor correlation of central
      green-light FAF intensity with CRT, IS/OS layer integrity or RPE-IS/OS layer
      thickness in diabetic patients with or without DME and its various subtypes.
      Thus, central green-light FAF is not suitable for detection of retinal thickening
      in DME.

PMID- 23549661
TI  - Nurse staffing and NICU infection rates.
AB  - IMPORTANCE: There are substantial shortfalls in nurse staffing in US neonatal
      intensive care units (NICUs) relative to national guidelines. These are
      associated with higher rates of nosocomial infections among infants with very low
      birth weights. OBJECTIVE: To study the adequacy of NICU nurse staffing in the
      United States using national guidelines and analyze its association with infant
      outcomes. DESIGN: Retrospective cohort study. Data for 2008 were collected by web
      survey of staff nurses. Data for 2009 were collected for 4 shifts in 4 calendar
      quarters (3 in 2009 and 1 in 2010). SETTING: Sixty-seven US NICUs from the
      Vermont Oxford Network, a national voluntary network of hospital NICUs.
      PARTICIPANTS: All inborn very low-birth-weight (VLBW) infants, with a NICU stay
      of at least 3 days, discharged from the NICUs in 2008 (n = 5771) and 2009 (n =
      5630). All staff-registered nurses with infant assignments. EXPOSURES: We
      measured nurse understaffing relative to acuity-based guidelines using 2008
      survey data (4046 nurses and 10 394 infant assignments) and data for 4 complete
      shifts (3645 nurses and 8804 infant assignments) in 2009-2010. MAIN OUTCOMES AND
      MEASURES: An infection in blood or cerebrospinal fluid culture occurring more
      than 3 days after birth among VLBW inborn infants. The hypothesis was formulated
      prior to data collection. RESULTS: Hospitals understaffed 31% of their NICU
      infants and 68% of high-acuity infants relative to guidelines. To meet minimum
      staffing guidelines on average would require an additional 0.11 of a nurse per
      infant overall and 0.34 of a nurse per high-acuity infant. Very low-birth-weight
      infant infection rates were 16.4% in 2008 and 13.9% in 2009. A 1 standard
      deviation-higher understaffing level (SD, 0.11 in 2008 and 0.08 in 2009) was
      associated with adjusted odds ratios of 1.39 (95% CI, 1.19-1.62; P < .001) in
      2008 and 1.40 (95% CI, 1.19-1.65; P < .001) in 2009. CONCLUSIONS AND RELEVANCE:
      Substantial NICU nurse understaffing relative to national guidelines is
      widespread. Understaffing is associated with an increased risk for VLBW
      nosocomial infection. Hospital administrators and NICU managers should assess
      their staffing decisions to devote needed nursing care to critically ill infants.

PMID- 23549662
TI  - Continuous one-pot synthesis of sandwich structured core-shell particles and
      transformation to yolk-shell particles.
AB  - Scalable continuous ultrasonic spray pyrolysis is used to develop a facile one
      pot method of synthesizing sandwich structured core-shell particles consisting of
      a Pd core, a V2O5 inner layer, and a porous SiO2 outer layer. Pd@SiO2 yolk-shell
      particles are easily formed by removing the V2O5 inner layer.

PMID- 23549660
TI  - Motor-sensory recalibration modulates perceived simultaneity of cross-modal
      events at different distances.
AB  - A popular model for the representation of time in the brain posits the existence
      of a single, central-clock. In that framework, temporal distortions in perception
      are explained by contracting or expanding time over a given interval. We here
      present evidence for an alternative account, one which proposes multiple
      independent timelines coexisting within the brain and stresses the importance of
      motor predictions and causal inferences in constructing our temporal
      representation of the world. Participants judged the simultaneity of a beep and
      flash coming from a single source at different distances. The beep was always
      presented at a constant delay after a motor action, while the flash occurred at a
      variable delay. Independent shifts in the implied timing of the auditory stimulus
      toward the motor action (but not the visual stimulus) provided evidence against a
      central-clock model. Additionally, the hypothesis that the time between action
      and delayed effect is compressed (known as intentional binding) seems unable to
      explain our results: firstly, because actions and effects can perceptually
      reverse, and secondly because the recalibration of simultaneity remains even
      after the participant's intentional actions are no longer present. Contrary to
      previous reports, we also find that participants are unable to use distance cues
      to compensate for the relatively slower speed of sound when audio-visual events
      are presented in depth. When a motor act is used to control the distal event,
      however, adaptation to the delayed auditory signal occurs and subjective cross
      sensory synchrony is maintained. These results support the hypothesis that
      perceptual timing derives from and is calibrated by our motor interactions with
      the world.

PMID- 23549663
TI  - Functional block copolymer assemblies responsive to tumor and intracellular
      microenvironments for site-specific drug delivery and enhanced imaging
      performance.
AB  - Self-assembled nanostructures of amphiphilic and double hydrophilic block
      copolymers have been increasingly utilized as potent polymeric nanocarriers of
      therapeutic drugs, genes, bioactive molecules, and imaging/contrast agents due to
      improved water solubility, bioavailability, and extended blood circulation
      duration. Though passive and active targeted drug delivery strategies have long
      been proposed to promote desirable drug accumulation specifically at the disease
      sites, the introduction of stimuli-responsiveness into self-assembled block
      copolymer nanocarriers can additionally lead to controlled/triggered release of
      therapeutic/imaging agents into target pathological tissues and cells, with
      concomitant advantages of enhanced delivery efficiency and therapeutic efficacy.
      Appropriately designed stimuli-responsive block copolymer assemblies can exhibit
      chemical structure transformation, microstructural rearrangement and inversion,
      or even disassembly into unimers or smaller ones under external stimuli such as
      pH, temperature, ion strength, redox potential, light, electric, and magnetic
      fields, and specific bioactive molecules and metabolites. Compared to normal
      tissues, pathological sites such as tumor tissues typically exhibit vascular
      abnormalities, weak acidity (~pH 6.8), abnormal temperatures, over-expressed
      proteins and enzymes, hypoxia, high levels of metabolites and reactive small
      molecule species, etc. Moreover, upon cellular uptake, drug-loaded polymeric
      nanocarriers will be subjected to intracellular pH gradients (pH 5.9-6.2 in early
      endosomes and pH 5.0-5.5 in late endosomes and lysosomes) and redox and H2O2
      gradients within different cell organelles and the cytosol. Thus, block copolymer
      nanocarriers responsive to the above described bio-relevant stimuli or
      biochemical signals characteristic of pathologic tissues and cells will provide
      an alternative type of "active targeting" strategy, which can be utilized to
      further boost therapeutic efficacy and imaging sensitivity via disease site
      specific delivery and controlled release. A variety of extracellular or
      intracellular stimuli innate to disease sites, such as mildly acidic pH,
      temperature, enzymes (matrix metalloproteinase, beta-glucuronidase, and
      phosphatase), oxidative/reductive microenvironments, and abnormal levels of
      bioactive molecules or metabolites, have been utilized for this purpose. In this
      review, we summarize recent advances in stimuli-responsive block copolymer
      assemblies which are responsive to tumor and intracellular microenvironments and
      their applications in anticancer drug delivery and enhanced imaging sensitivity.

PMID- 23549664
TI  - Phenotypic detection of plasmid-acquired AmpC in Escherichia coli--evaluation of
      screening criteria and performance of two commercial methods for the phenotypic
      confirmation of AmpC production.
AB  - The phenotypic detection of plasmid-acquired AmpC (pAmpC) in Escherichia coli is
      challenging, and molecular methods are required for confirmation. In addition to
      cefoxitin resistance, multiresistance and high-level resistance to cephalosporins
      have both been suggested as criteria for targeting isolates with pAmpC, but data
      to support these proposed criteria are lacking. A Swedish collection of 378
      isolates with either putative chromosomal hyperproduction of AmpC (cAmpC) or
      pAmpC were subjected to disk diffusion and minimum inhibitory concentration (MIC)
      determination with the Etest. The frequency of resistance to gentamicin,
      ciprofloxacin, and trimethoprim among cAmpC and pAmpC was compared to elucidate
      the issue of multidrug resistance. Lastly, methods for the phenotypic
      confirmation of pAmpC were compared. One in-house disk diffusion method, one
      method employing NeoSensitabs (Rosco), and one Etest method (bioMerieux) were
      compared. The analysis of histograms based on both disk diffusion and the Etest
      showed that resistance [according to the European Committee on Antimicrobial
      Susceptibility Testing (EUCAST)] to cefotaxime and/or ceftazidime occurred in
      almost all isolates. By coining resistance instead of non-susceptibility, the
      number of isolates required to subject to phenotypic testing/genotypic
      confirmation dropped by more than 40 %, without compromising the sensitivity
      substantially. Further, almost 70 % of isolates with pAmpC were non-multidrug
      resistant, clearly indicating that this is an inappropriate criterion for further
      investigation. The phenotypic tests all had more than 90 % sensitivity, and the
      best sensitivities were obtained with the in-house method and with the
      ceftazidime +/- cloxacillin NeoSensitab. In conclusion, clinical resistance to
      cefotaxime and/or ceftazidime seems to be an appropriate criterion for pAmpC
      screening, and several phenotypic methods perform well for the phenotypic
      confirmation of AmpC production prior to genotypic confirmation.

PMID- 23549665
TI  - PFO Closure for Cryptogenic Stroke: Review of New Data and Results.
AB  - OPINION STATEMENT: Observational studies over 20 years have suggested that a
      patent foramen ovale (PFO) is an important cause of cryptogenic stroke in young
      individuals; case series and registries suggest that PFO closure confers superior
      protection from recurrent transient ischemic attack (TIA) and stroke. Recently
      completed randomized clinical trials did not confirm this hypothesis, but have
      provided reassurance that the risk of recurrent stroke is low at 1.5 %/yr. A
      target subset that may benefit are those with ischemic stroke, a large right-to
      left shunt, and an atrial septal aneurysm. Further study is needed to determine
      the optimum strategy to reduce the long-term stroke risk in a lifetime of varying
      situational risk factors and temporary interruptions of medical therapies.

PMID- 23549666
TI  - Factorial and diagnostic validity of the Beck Depression Inventory-II (BDI-II) in
      Croatian primary health care.
AB  - The aim of this study was to examine the factorial and diagnostic validity of the
      Beck Depression Inventory-Second Edition (BDI-II) in Croatian primary health
      care. Data were collected using a medical outpatient sample (N = 314).
      Reliability measured by internal consistency proved to be high. While the Velicer
      MAP Test showed that extraction of only one factor is satisfactory, confirmatory
      factor analysis indicated the best fit for a 3-factor structure model consisting
      of cognitive, affective and somatic dimensions. Receiver operating
      characteristics (ROC) analysis demonstrated the BDI-II to have a satisfactory
      diagnostic validity in differentiating between healthy and depressed individuals
      in this setting. The area under the curve (AUC), sensitivity and specificity were
      high with an optimal cut-off score of 15/16. The implications of these findings
      are discussed regarding the use of the BDI-II as a screening instrument in
      primary health care settings.

PMID- 23549667
TI  - Bis-triazolyl indoleamines as unique "off-approach-on" chemosensors for copper
      and fluorine.
AB  - Bis-triazolyl indoleamine-based chemosensors that respond to copper, and then
      fluorine as presumably facilitated by the high-affinity interaction between F(-)
      and the NH-proton of indole, are reported. Remarkable fluorimetric as well as
      colorimetric alternations upon the specific ligand-ion recognitions were
      observed.

PMID- 23549668
TI  - Charge site mass spectra: conformation-sensitive components of the electron
      capture dissociation spectrum of a protein.
AB  - A conventional electron capture dissociation (ECD) spectrum of a protein is
      uniquely characteristic of the first dimension of its linear structure. This
      sequence information is indicated by summing the primary c (m+) and z (m+*)
      products of cleavage at each of its molecular ion's inter-residue bonds. For
      example, the ECD spectra of ubiquitin (M + nH)(n+) ions, n = 7-13, provide
      sequence characterization of 72 of its 75 cleavage sites from 1843 ions in seven
      c ((1-7)+) and eight z ((1-8)+*) spectra and their respective complements. Now we
      find that each of these c/z spectra is itself composed of "charge site (CS)"
      spectra, the c (m+) or z (m+*) products of electron capture at a specific
      protonated basic residue. This charge site has been H-bonded to multiple other
      residues, producing multiple precursor ion forms; ECD at these residues yields
      the multiple products of that CS spectrum. Closely similar CS spectra are often
      formed from a range of charge states of ubiquitin and KIX ions; this indicates a
      common secondary conformation, but not the conventional alpha-helicity postulated
      previously. CS spectra should provide new capabilities for comparing regional
      conformations of gaseous protein ions and delineating ECD fragmentation pathways.

PMID- 23549669
TI  - The incremental effect of psychosocial workplace factors on the development of
      neck and shoulder disorders: a systematic review of longitudinal studies.
AB  - BACKGROUND: To systematically analyse evidence on the incremental effect of work
      related psychosocial risk factors on the development of neck and shoulder
      disorders, as reported in longitudinal studies. METHODS: A systematic literature
      search was conducted in three data bases (MEDLINE, EMBASE, and PsychINFO) until
      May 2009. The quality assessment leading to a methodological quality score of the
      included studies was conducted by two independent reviewers using a standardised
      checklist. Criteria for the evaluation of evidence were established.
      Heterogeneity analyses were conducted. RESULTS: Altogether 18 prospective
      longitudinal studies were included in the analysis. Potential psychosocial risk
      factors were mainly based on the job demand control (support) model by Karasek
      (1998). Study results were too heterogeneous to deduce pooled risk estimates. But
      the weight of evidence was strong for an incremental effect of job demands, job
      control, social support, and job strain, on the development of neck and/or
      shoulder disorders. CONCLUSION: While we found evidence for an incremental effect
      of different psychosocial work factors (in addition to the effect of physical job
      factors), these results have to be interpreted carefully in order to support the
      notion that psychological factors can have an independent causal influence on the
      development of musculoskeletal disorders. Nevertheless, our findings are
      important for the development of preventive strategies, as they stress the need
      for preventive approaches that tackle both physical and psychosocial factors.
      Future research is warranted to consolidate and strengthen the results of this
      review.

PMID- 23549670
TI  - The in vitro pharmacological profile of TD-1211, a neutral opioid receptor
      antagonist.
AB  - The clinical efficacy of opioid receptor antagonists for the treatment of opioid
      induced constipation (OIC) is established. Peripherally selective antagonists are
      intended to provide OIC symptom relief without compromising the analgesic effects
      of centrally penetrant opioid agonists. We describe the in vitro profile of a
      novel opioid receptor antagonist, TD-1211, at recombinant (human MU and delta,
      and guinea pig kappa) and rodent native opioid receptors. TD-1211 bound with high
      affinity to human recombinant MU and delta, and guinea pig kappa receptors
      expressed in CHO-K1 cells (pK d = 9.7, 8.6, and 9.9, respectively). The in vitro
      receptor selectivity of TD-1211 (MU ~ kappa > delta) is similar to that for the
      peripherally-selective opioid receptor antagonist methylnaltrexone, but contrasts
      with the MU selectivity of alvimopan. Functionally, TD-1211 behaved as an
      antagonist at all three receptor types in both recombinant expression systems (pK
      b = 9.6, 8.8 and 9.5, at MU, delta, and kappa, respectively) and rodent native
      tissue preparations (MU and kappa pA2s = 10.1 and 8.8, respectively (guinea pig
      ileum), and delta pK b = 8.4 (hamster vas deferens)). TD-1211 displayed a high
      degree of selectivity for opioid receptors over a broad panel of cellular
      targets. These in vitro data justified investigation of the preclinical in vivo
      activity of TD-1211 (Armstrong et al., Naunyn-Schmiedeberg's Arch Pharm, 2013).

PMID- 23549672
TI  - Is there visceral adipose tissue (VAT) intracellular hypercortisolism in human
      obesity?
AB  - The fact that obesity is a prominent feature of Cushing's syndrome (systemic
      hypercortisolism of adrenocortical origin) stimulated a 40-year search for
      evidence of systemic hypercortisolism in human obesity. That search has failed to
      find such evidence. For the past 15 years, however, studies have been done to
      evaluate a possible alternative type of hypercortisolism in obesity, namely
      visceral adipose tissue (VAT) intracellular hypercortisolism. The current review
      summarizes the evidence published so far about this possibility. There have been
      three types of evidence studied: direct measurement of the VAT levels of 11beta
      hydroxysteroid dehydrogenase type I (11-HSD-1), which converts biologically
      inactive cortisone to biologically active cortisol; direct measurement of
      splanchnic cortisol production; and evaluation of the effect of a specific
      inhibitor of 11-HSD-1 on metabolic abnormalities associated with obesity,
      particularly diabetes mellitus. The results are complex and difficult to
      interpret. Our conclusion is that the presence of VAT intracellular
      hypercortisolism in human obesity is possible but unlikely.

PMID- 23549671
TI  - Influence of phosphodiesterases and cGMP on cAMP generation and on
      phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in
      porcine left atrium.
AB  - Our objective was to investigate the role of phosphodiesterase (PDE)3 and PDE4
      and cGMP in the control of cAMP metabolism and of phosphorylation of troponin I
      (TnI) and phospholamban (PLB) when 5-HT4 receptors are activated in pig left
      atrium. Electrically paced porcine left atrial muscles, mounted in organ baths,
      received stimulators of particulate guanylyl cyclase (pGC) or soluble guanylyl
      cyclase (sGC) and/or specific PDE inhibitors followed by 5-HT or the 5-HT4
      receptor agonist prucalopride. Muscles were freeze-clamped at different moments
      of exposure to measure phosphorylation of the cAMP/protein kinase A targets TnI
      and PLB by immunoblotting and cAMP levels by enzyme immunoassay. Corresponding
      with the functional results, 5-HT only transiently increased cAMP content, but
      caused a less quickly declining phosphorylation of PLB and did not significantly
      change TnI phosphorylation. Under combined PDE3 and PDE4 inhibition, the 5-HT
      induced increase in cAMP levels and PLB phosphorylation was enhanced and
      sustained, and TnI phosphorylation was now also increased. Responses to
      prucalopride per se and the influence thereupon of PDE3 and PDE4 inhibition were
      similar except that responses were generally smaller. Stimulation of pGC together
      with PDE4 inhibition increased 5-HT-induced PLB phosphorylation compared to 5-HT
      alone, consistent with functional responses. sGC stimulation hastened the fade of
      inotropic responses to 5-HT, while cAMP levels were not altered. PDE3 and PDE4
      control the cAMP response to 5-HT4 receptor activation, causing a dampening of
      downstream signalling. Stimulation of pGC is able to enhance inotropic responses
      to 5-HT by increasing cAMP levels, while sGC stimulation decreases contraction to
      5-HT cAMP independently. 

PMID- 23549673
TI  - Long-term effects of perinatal androgenization on reproductive parameters of male
      rat offspring androgenization and male rat reproduction.
AB  - It is known that during sex differentiation, fetal androgens are critical
      determinants of the male phenotype. Although testosterone is necessary for normal
      development of male sexual behavior, perinatal androgen treatment can result in
      disruption of normal male sexual reproduction. Pregnant Wistar rats were
      administered either corn oil (vehicle) or testosterone propionate at 0.2 mg/kg
      from gestational day 12 until the end of lactation and the reproductive function
      of male offspring was evaluated at 90 (adulthood) and 270 (middle age) days of
      age. Perinatal androgenization in the rat provoked a reduction in sperm
      production and reserves in adulthood that did not affect fertility and did not
      persist at more advanced ages, as shown by the results at post-natal day 270. If
      perinatal androgenization promotes similar effects in humans of reproductive age,
      the results of the present work can impact male reproduction health, given the
      less efficient spermatogenesis and lower sperm reserves in the human epididymis,
      compared to rodents. 

PMID- 23549674
TI  - Mechanism of insulin resistance in normal pregnancy.
AB  - Normal pregnancy is associated with insulin resistance although the mechanism is
      not understood. Increased intramyocellular lipid is closely associated with the
      insulin resistance of type 2 diabetes and obesity, and the aim of this study was
      to determine whether this was so for the physiological insulin resistance of
      pregnancy. Eleven primiparous healthy pregnant women (age: 27-39 years, body mass
      index 24.0+/-3.1 kg/m2) and no personal or family history of diabetes underwent
      magnetic resonance studies to quantify intramyocellular lipid, plasma lipid
      fractions, and insulin sensitivity. The meal-related insulin sensitivity index
      was considerably lower in pregnancy (45.6+/-9.9 vs. 193.0+/-26.1; 10(-4)
      dl/kg/min per pmol/l, p=0.0002). Fasting plasma triglyceride levels were elevated
      3-fold during pregnancy (2.3+/-0.2 vs. 0.8+/-0.1 mmol/l, p<0.01) and the low
      density density lipoprotein fraction, responsible for fatty acid delivery to
      muscle and other tissues, was 6-fold elevated (0.75+/-0.43 vs. 0.12+/-0.09
      mmol/l; p=0.001). However, mean intramyocellular lipid concentrations of the
      soleus muscle were not different during pregnancy (20.0+/-2.3 vs. 19.1+/-3.2
      mmol/l, p=0.64). The pregnancy effect on muscle insulin resistance is distinct
      from that underlying type 2 diabetes.

PMID- 23549675
TI  - Protein normalization in different adipocyte models and dependence on cell size.
AB  - Various in vitro models are commonly used to study adipose tissue function.
      However, methods for protein normalization in dependence of differentiation and
      fat cell size are poorly defined. Therefore, the aim of this study was to
      characterize frequently used housekeepers during adipose differentiation in fat
      cells of varying cell size and between different subjects to allow a reliable and
      robust data interpretation. Human preadipocytes, SGBS, 3T3-L1, and mature cells
      were used to study the housekeeper profile. Glyceraldehyde-3-phosphate
      dehydrogenase was the most stable internal control in human preadipocytes,
      whereas all others showed substantial variation. In SGBS and 3T3-L1 cells none of
      the housekeepers revealed stable protein levels during differentiation. In mature
      adipocytes GAPDH and alpha-tubulin were found to be suitable as internal loading
      controls. Importantly, there was no substantial variation between different
      donors. However, Coomassie-staining turned out to represent an appropriate
      alternative as a stable and highly sensitive internal standard for all cell
      models tested. In conclusion, standard housekeeping proteins have substantial
      limitations in studies of adipogenesis and in dependence of fat cell size.
      Coomassie-staining turned out to be a sensitive and stable alternative as
      internal control for western blot studies during adipogenesis. However, inter
      subject variability was low for the investigated housekeeper. 

PMID- 23549676
TI  - An active role for steroid-binding globulins: an update.
AB  - It has been 7 years (can it really be that long?) since we co-edited a volume
      (#38) of Hormone and Metabolic Research that focused on evidence that steroid
      binding globulins play an active role in the actions of steroids. There has been
      considerable progress in identifying the location, the physiological actions, and
      of determining the role of binding globulins in the actions of steroids and
      identifying a membrane-associated receptor for a binding protein since then and
      this review will discuss this progress. 

PMID- 23549677
TI  - Risk factors for peripherally inserted central venous catheter complications in
      children.
AB  - IMPORTANCE: Peripherally inserted central venous catheters (PICCs) are prone to
      infectious, thrombotic, and mechanical complications. These complications are
      associated with morbidity, so data are needed to inform quality improvement
      efforts. OBJECTIVES: To characterize the epidemiology of and to identify risk
      factors for complications necessitating removal of PICCs in children. DESIGN:
      Cohort study. SETTING: Johns Hopkins Children's Center, Baltimore, Maryland.
      PARTICIPANTS: Hospitalized children who had a PICC inserted outside of the
      neonatal intensive care unit (ICU) from January 1, 2003, through December 31,
      2009. MAIN OUTCOME MEASURES: Complications necessitating PICC removal as recorded
      by the PICC Team. RESULTS: During the study period, 2574 PICCs were placed in
      1807 children. Complications necessitating catheter removal occurred in 534 PICCs
      (20.8%) during 46 021 catheter-days (11.6 complications per 1000 catheter-days).
      These included accidental dislodgement (4.6%), infection (4.3%), occlusion
      (3.7%), local infiltration (3.0%), leakage (1.5%), breakage (1.4%), phlebitis
      (1.2%), and thrombosis (0.5%). From 2003 to 2009, complications decreased by 15%
      per year (incidence rate ratio [IRR], 0.85; 95% CI, 0.81-0.89). In adjusted
      analysis, all noncentral PICC tip locations-midline (IRR 4.59, 95% CI, 3.69
      5.69), midclavicular (2.15; 1.54-2.98), and other (3.26; 1.72-6.15)-compared with
      central tip location were associated with an increased risk of complications.
      Pediatric ICU exposure and age younger than 1 year were independently associated
      with complications necessitating PICC removal. CONCLUSIONS AND RELEVANCE:
      Noncentral PICC tip locations, younger age, and pediatric ICU exposure were
      independent risk factors for complications necessitating PICC removal. Despite
      reductions in PICC complications, further efforts are needed to prevent PICC
      associated complications in children.

PMID- 23549678
TI  - A versatile platform for highly sensitive detection of kinase activity based on
      metal ion-mediated FRET using an anionic conjugated polymer.
AB  - An anionic fluorescent conjugated polymer (PFPaa), coupled with the metal ion
      mediated fluorescence resonance energy transfer, has been used to design a
      versatile platform for homogeneous detection of protein kinase activity.

PMID- 23549680
TI  - Clinical evaluation of the efficiency of low-level laser therapy for oral lichen
      planus: a prospective case series.
AB  - Oral lichen planus (OLP) is an inflammatory disease that can be painful, mainly
      in the atrophic and erosive forms. Numerous drugs have been used with dissimilar
      results, but most treatments are empirical. However, to date, the most commonly
      employed and useful agents for the treatment of OLP are topical corticosteroids.
      The study objective was to detail the clinical effectiveness of low-level laser
      therapy (LLLT) for the management of OLP unresponsive to standard topical
      therapy. The authors studied a prospective cohort of 30 patients affected by OLP,
      who received biostimulation with a 980-nm gallium-aluminum-arsenide (GaAIAs)
      diode laser (DM980, distributed by DMT S.r.l., Via Nobel 33, 20035, Lissone,
      Italy). Outcome variables, statistically evaluated, were: the size of lesions;
      visual analogue score of pain and stability of the therapeutic results in the
      follow-up period. Eighty-two lesions were treated. We reported significant
      reduction in clinical scores of the treated lesions and in reported pain. No
      detailed complications or therapy side effects were observed during the study. As
      previously reported by our group with a preliminary report, this study suggests
      that LLLT could be a possible treatment choice for patients with unresponsive
      symptomatic OLP, also reducing the possible invasiveness correlated with other
      therapies. 

PMID- 23549681
TI  - The effect of estrogen on prolidase-dependent regulation of HIF-1alpha expression
      in breast cancer cells.
AB  - The role of estrogen in breast cancer progression and activation of prolidase
      activity and HIF-1alpha led us to study the effect of estrogen on nuclear HIF
      1alpha expression in breast cancer estrogen-dependent MCF-7 and estrogen
      independent MDA-MB-231 cells. We have found that in MCF-7 cells (expressing alpha
      and beta estrogen receptor) cultured without estrogen receptor activator (phenol
      red, estradiol), HIF-1alpha was down-regulated, compared to the cells cultured
      with estrogen receptor activator. This effect was not observed in MDA-MB-231
      cells (expressing only beta estrogen receptor), suggesting that alpha estrogen
      receptor is involved in down-regulation of HIF-1alpha. However, in MDA-MB-231
      cells (expressing high prolidase activity) cultured in the presence of prolidase
      substrates, Gly-Pro or Gly-HyPro, HIF-1alpha expression was induced in a dose
      dependent manner, independently of estrogen receptor activation. In MCF-7 cells
      (with constitutively low prolidase activity) the effect of studied
      iminodipeptides on HIF-1alpha expression was much less pronounced but it was
      estrogen-dependent, showing importance of prolidase activity in mechanism of this
      process. The data were supported by confocal microscopy bio-imaging of HIF-1alpha
      in nucleus of MCF-7 and MDA-MB-231 cells that were cultured in the presence and
      absence of estrogen activator and prolidase substrates. It suggests that estrogen
      receptor may represent important therapeutic target in pharmacotherapy of
      estrogen receptor positive breast cancer, while ECM degradation enzymes,
      including prolidase may represent target in pharmacotherapy of estrogen receptor
      negative breast cancers.

PMID- 23549682
TI  - Survival ethics in the real world: the research university and sustainable
      development.
AB  - We discuss how academically-based interdisciplinary teams can address the extreme
      challenges of the world's poorest by increasing access to the basic necessities
      of life. The essay's first part illustrates the evolving commitment of research
      universities to develop ethical solutions for populations whose survival is at
      risk and whose quality of life is deeply impaired. The second part proposes a
      rationale for university responsibility to solve the problems of impoverished
      populations at a geographical remove. It also presents a framework for
      integrating science, engineering and ethics in the efforts of multidisciplinary
      teams dedicated to this task. The essay's third part illustrates the efforts of
      Howard University researchers to join forces with African university colleagues
      in fleshing out a model for sustainable and ethical global development. 

PMID- 23549683
TI  - PandaEPL: a library for programming spatial navigation experiments.
AB  - Recent advances in neuroimaging and neural recording techniques have enabled
      researchers to make significant progress in understanding the neural mechanisms
      underlying human spatial navigation. Because these techniques generally require
      participants to remain stationary, computer-generated virtual environments are
      used. We introduce PandaEPL, a programming library for the Python language
      designed to simplify the creation of computer-controlled spatial-navigation
      experiments. PandaEPL is built on top of Panda3D, a modern open-source game
      engine. It allows users to construct three-dimensional environments that
      participants can navigate from a first-person perspective. Sound playback and
      recording and also joystick support are provided through the use of additional
      optional libraries. PandaEPL also handles many tasks common to all cognitive
      experiments, including managing configuration files, logging all internal and
      participant-generated events, and keeping track of the experiment state. We
      describe how PandaEPL compares with other software for building spatial
      navigation experiments and walk the reader through the process of creating a
      fully functional experiment. 

PMID- 23549679
TI  - Cytokines as biomarkers of nanoparticle immunotoxicity.
AB  - Nanoscale objects, whether of biologic origin or synthetically created, are being
      developed into devices for a variety of bionanotechnology diagnostic and
      pharmaceutical applications. However, the potential immunotoxicity of these
      nanomaterials and mechanisms by which they may induce adverse reactions have not
      received sufficient attention. Nanomaterials, depending on their characteristics
      and compositions, can interact with the immune system in several ways and either
      enhance or suppress immune system function. Cytokines perform pleiotropic
      functions to mediate and regulate the immune response and are generally
      recognized as biomarkers of immunotoxicity. While the specificity and validity of
      certain cytokines as markers of adverse immune response has been established for
      chemicals, small and macromolecular drugs, research on their applicability for
      predicting and monitoring the immunotoxicity of engineered nanomaterials is still
      ongoing. The goal of this review is to provide guidelines as to important
      cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials
      and to highlight the role of those cytokines in mediating adverse reactions,
      which is of particular importance for the clinical development of
      nanopharmaceuticals and other nanotechnology-based products. Importantly, the
      rational design of nanomaterials of low immunotoxicity will be discussed,
      focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming
      materials and the embedded cargoes.

PMID- 23549684
TI  - Four years follow-up of 101 children with melamine-related urinary stones.
AB  - The melamine-contaminated milk powder incidence occurred in China in 2008. Many
      studies have been published regarding the epidemiology, clinical symptoms,
      diagnosis and treatment of melamine-related urinary stones. The objective of this
      study is to follow-up the effects of melamine-contaminated milk powder
      consumption on kidney and body growth in children with melamine-related urinary
      stones 4 years ago. One hundred and one children with melamine-related urinary
      stones were followed up by urinalysis, renal function tests and urinary
      ultrasonography. The data of body weight and height, clinical signs and
      complications were collected. Eighty normal children without the history of
      consuming melamine-contaminated milk powder were collected as controls. Eighty
      one children with melamine-related urinary stones were successfully followed up.
      Of 45 cases with melamine-related urinary stones treated conservatively after
      discharge, 34 disappeared completely, 6 dissolved partially, 1 increased in size
      and 4 did not change at 4 years follow-up. The percentages of under-height and
      under-weight infants were significantly higher in melamine-related urinary stones
      group compared to the controls, respectively (p < 0.05). Routine blood, renal and
      bladder function tests as well as urinalysis were normal in all children. No
      urological tumors were detected. No noticeable impact of melamine-related urinary
      stones on kidney and bladder was found at 4 years follow-up. However, whether or
      not melamine-related urinary stones had effect on body growth needs follow-up in
      future.

PMID- 23549688
TI  - Changes in running mechanics and spring-mass behaviour during a 5-km time trial.
AB  - Research into the biomechanical manifestation of fatigue during exhaustive runs
      is increasingly popular but additional understanding of the adaptation of the
      spring-mass behaviour during the course of strenuous, self-paced exercises
      continues to be a challenge in order to develop optimized training and injury
      prevention programs. This study investigated continuous changes in running
      mechanics and spring-mass behaviour during a 5-km run. 12 competitive triathletes
      performed a 5-km running time trial (mean performance: 17 min 30 s) on a 200 m
      indoor track. Vertical and anterior-posterior ground reaction forces were
      measured every 200 m by a 5-m long force platform system, and used to determine
      spring-mass model characteristics. After a fast start, running velocity
      progressively decreased (- 11.6%; P<0.001) in the middle part of the race before
      an end spurt in the final 400-600 m. Stride length (- 7.4%; P<0.001) and
      frequency (- 4.1%; P=0.001) decreased over the 25 laps, while contact time (+
      8.9%; P<0.001) and total stride duration (+ 4.1%; P<0.001) progressively
      lengthened. Peak vertical forces (- 2.0%; P<0.01) and leg compression (- 4.3%;
      P<0.05), but not centre of mass vertical displacement (+ 3.2%; P>0.05), decreased
      with time. As a result, vertical stiffness decreased (- 6.0%; P<0.001) during the
      run, whereas leg stiffness changes were not significant (+ 1.3%; P>0.05). Spring
      mass behaviour progressively changes during a 5-km time trial towards
      deteriorated vertical stiffness, which alters impact and force production
      characteristics. 

PMID- 23549689
TI  - NFAT isoforms regulate muscle fiber type transition without altering CaN during
      aerobic training.
AB  - The purpose of this study was to determine whether the aerobic training-induced
      fiber-type transition in different muscles is associated with alterations in NFAT
      isoforms gene expression. We hypothesized that the aerobic training-induced fiber
      type transition would be mediated by NFATc1-c3 isoforms without altering the CaN
      expression. Male Wistar rats (80 days old) were divided into a trained group (T;
      n=8) that underwent an 8-wk swimming endurance training program (5 days/week) and
      a control group (C; n=8). After the experimental period, the animals were
      sacrificed, and the soleus (SOL) and plantaris (PL) muscles were collected for
      morphometrical, histochemical and molecular analyses. Aerobic training induced a
      type I-to-type IIA fiber transition in the SOL muscle and a type IIB-to-type IIA
      fiber transition in the PL muscle, which were concomitant with a significant
      (p<0.05) increase in NFATc1-c3 gene expression in both the SOL and PL muscles. In
      contrast, the expression levels of calcineurin (CaN) and NFATc4 remained
      unchanged. Therefore, our results showed that fiber type switching induced by
      aerobic training is mediated by NFATc1-c3 isoforms without altering the CaN
      expression. 

PMID- 23549690
TI  - Vertical ground reaction force during water exercises performed at different
      intensities.
AB  - The aim of the present study was to compare the peak vertical ground reaction
      force (V-GRF(peak)) and impulse of women performing water aerobic exercises at
      different intensities in aquatic and dry land environments. 15 young women
      performed 1 session in each environment consisting of 3 water aerobic exercises
      (stationary running, frontal kick and cross country skiing) performed at 3
      cadences (first ventilatory threshold, second ventilatory threshold and maximum
      effort, as determined during exercise in water) in a randomized order. 2-way and
      3-way repeated measures ANOVA were used to analyze the impulse and V-GRF(peak),
      respectively. Significantly lower values of V-GRF(peak) and impulse (p<0.001)
      were observed for the aquatic environment. Significant differences were observed
      among all cadences for V-GRF(peak) and impulse (p<0.001) in both environments
      except for the V-GRF(peak) between the cadences corresponding to the second
      ventilatory threshold and maximum effort in the aquatic environment. In addition,
      significantly lower V-GRF(peak) values in the aquatic environment were found for
      cross country skiing compared to the other exercises (p<0.001). Thus, water
      exercises are safe for people that need to minimize vertical ground reaction
      force; however, an important issue to be considered during water aerobics
      training is the exercise and intensity to be prescribed.

PMID- 23549691
TI  - Monitoring training in elite soccer players: systematic bias between running
      speed and metabolic power data.
AB  - We compared measurements of high-intensity activity during field-based training
      sessions in elite soccer players of different playing positions. Agreement was
      appraised between measurements of running speed alone and predicted metabolic
      power derived from a combination of running speed and acceleration. Data was
      collected during a 10-week phase of the competitive season from 26 English
      Premier League outfield players using global positioning system technology. High
      intensity activity was estimated using the total distance covered at speeds >14.4
      km . h-1 (TS) and the equivalent metabolic power threshold of >20 W . kg-1 (TP),
      respectively. We selected 0.2 as the -minimally important standardised difference
      between methods. Mean training session TS was 478+/-300 m vs. 727+/-338 m for TP
      (p<0.001). This difference was greater for central defenders (~ 85%) vs. wide
      defenders and attackers (~ 60%) (p<0.05). The difference between methods also
      decreased as the proportion of high-intensity distance within a training session
      increased (R2=0.43; p<0.001). We conclude that the high-intensity demands of
      soccer training are underestimated by traditional measurements of running speed
      alone, especially in training sessions or playing positions associated with less
      high-intensity activity. Estimations of metabolic power better inform the coach
      as to the true demands of a training session.

PMID- 23549692
TI  - The effect of isokinetic testing speed on the reliability of muscle fatigue
      indicators during a hip abductor-adductor fatigue protocol.
AB  - The aim of this study was to investigate the reliability of fatigue indicators
      calculated from peak torque and total work during isokinetic speeds of 60, 90,
      120 and 180 degrees  . s-1 during a hip fatigue protocol. 10 males suffering from
      a history of unilateral functional ankle instability and 10 male healthy controls
      performed 5 maximal concentric contractions on an isokinetic dynamometer.
      Following a 4 min rest period subjects were instructed to perform repeated
      maximal concentric contractions to fatigue, which was defined as 3 consecutive
      repetitions below 50% of the maximum peak torque value. Each testing speed was
      randomised with 24 h between speeds. The subjects were asked to return to the
      laboratory 7 days later to repeat the 4 speeds, with 24 h between speeds. Muscle
      fatigue was determined for each testing speed by the fatigue index, the percent
      decrease in performance and the slope of the regression equation. The most
      reliable fatigue determination method was the slope of the regression equation,
      when testing at a speed of 120 degrees  . s-1. It is recommended that future
      investigators examine and plot their data before choosing the slope of the
      regression equation as their fatigue indicator, as a linear model is required. 

PMID- 23549693
TI  - Effects of concurrent training on explosive strength and VO(2max) in prepubescent
      children.
AB  - The purpose of this study was to compare the effects of an 8-weeks training
      period of resistance training alone (GR), combined resistance and endurance
      training (GCON) and a control group (GC) on explosive strength and V(O2max) in a
      large sample of prepubescent boys and girls. 125 healthy children (58 boys, 67
      girls), aged 10-11 years old (10.8+/-0.4 years) were assigned into 2 training
      groups to train twice a week for 8 weeks: GR (19 boys, 22 girls), GCON (21 boys,
      24 girls) and a control group (GC: 18 boys, 21 girls; no training program). A
      significant but medium-sized increase from pre- to the post-training in the
      vertical jump (Effect size=0.22, F=34.44, p<0.01) and V(O2max) (Effect size=0.19,
      F=32.89, p<0.01) was observed. A significant large increase in the 1 kg (Effect
      size=0.53, F=202.17, p<0.01) and 3 kg (Effect size=0.48, F=132.1, p<0.01) ball
      throwing, standing long jump (Effect size=0.53, F=72.93, p<0.01) and running
      speed (Effect size=0.45, F=122.21, p<0.01) was also observed. The training group
      (GR and GCON) and sex factors did not significantly influence the evolution of
      strength variables from pre- to the post-training. The V(O2max) increased
      significantly only in GCON. Concurrent training is equally effective on training
      induced explosive strength, and more efficient than resistance training only for
      V(O2max), in prepubescent boys and girls. This should be taken into consideration
      in order to optimize strength training school-based programs.

PMID- 23549694
TI  - Vibration or balance training on neuromuscular performance in osteopenic women.
AB  - Maintaining neuromuscular function in older age is an important topic for aging
      societies, especially for older women with low bone density who may be at risk of
      falls and bone fracture. This randomized controlled trial investigated the effect
      of resistive exercise with either whole-body vibration training (VIB) or
      coordination/balance training (BAL) on neuromuscular function (countermovement
      jump, multiple 1-leg hopping, sit-to-stand test). 68 postmenopausal women with
      osteopenia or osteoporosis were recruited for the study. 57 subjects completed
      the 9-month, twice weekly, intervention period. All subjects conducted 30 min of
      resistance exercise each training day. The VIB-group performed additional
      training on the Galileo vibration exercise device. The BAL-group performed
      balance training. An "intent-to-treat" analysis showed greater improvement in the
      VIB-group for peak countermovement power (p=0.004). The mean [95% confidence
      interval] effect size for this parameter was a  + 0.9[0.3 to 1.5] W/kg greater
      change in VIB than BAL after 9 months. In multiple 1-leg hopping, a significantly
      better performance in the VIB-group after the intervention period was seen on a
      "per-protocol" analysis only. Both groups improved in the sit-to-stand test. The
      current study provides evidence that short-duration whole-body vibration exercise
      can have a greater impact on some aspects of neuromuscular function in post
      menopausal women with low bone density than proprioceptive training. 

PMID- 23549695
TI  - Editorial--Thematic reviews. Series I: space physiology.

PMID- 23549696
TI  - Beyond 'vulnerable groups': contexts and dynamics of vulnerability.
AB  - This paper reviews approaches to vulnerability in public health, introducing a
      series of 10 papers addressing vulnerability in health in Africa. We understand
      vulnerability as simultaneously a condition and a process. Social inequalities
      are manifest in and exacerbate three key dimensions of vulnerability: the initial
      level of wellbeing, the degree of exposure to risk, and the capacity to manage
      risk effectively. We stress the dynamic interactions linking material and social
      deprivation, poverty, powerlessness and ill health: risks or shocks and their
      health impacts are intimately interconnected and reinforce each other in a cycle
      which in the absence of effective interventions, increases vulnerability. An
      inductive process which does not begin with an a priori definition or measurement
      of 'vulnerability' and which does not assume the existence of fixed 'vulnerable
      groups' allowed us both to re-affirm core aspects of existing conceptual
      frameworks, and to engage in new ways with literature specifically addressing
      vulnerability and resilience at the population level as well as with literature -
      for example in ecology, and on the concept of frailty in research on aging - with
      which researchers on health and poverty in Africa may not be familiar. We invite
      conceptual and empirical work on vulnerability in complex systems frameworks.
      These perspectives emphasize contexts and nonlinear causality thus supporting
      analyses of vulnerability and resilience as both markers and emergent properties
      of dynamic interactions. We accept a working definition of vulnerability, and
      recognize that some definable groups of people are more likely than others to
      suffer harm from exposure to health risks. But we suggest that the real work - at
      both intellectual and policy/political levels - lies in understanding and
      responding to the dynamics, meanings and power relations underlying actual
      instances and processes of vulnerability and harm.

PMID- 23549697
TI  - A spatial analysis of a community-based selection of indigents in Burkina Faso.
AB  - Over recent decades, Burkina Faso has improved the geographic accessibility of
      its health centres. However, patients are still required to pay point-of-service
      user fees, which excludes the most vulnerable from access to care. In 2010, 259
      village committees in the Ouargaye district selected 2649 indigents to be
      exempted from user fees. The 26 health centre management committees that fund
      this exemption retained 1097 of those selected indigents. Spatial analysis showed
      that the management committees retained the indigents who were geographically
      closer to the health centres, in contrast to the selections of the village
      committees which were more diversified. Using village committees to select
      indigents would seem preferable to using management committees. It is not yet
      known whether the management committees' selections were due to a desire to
      maximize the benefits of exemption by giving it to those most likely to use it,
      or to the fact that they did not personally know the indigents who were more
      geographically distant from them, or that some villages are not represented at
      the management committees.

PMID- 23549698
TI  - AIDS and the transition to adulthood of young seropositive women in Ouagadougou
      (Burkina Faso).
AB  - Since the early 1990 s, the means of attaining adult status have undergone a
      transformation due to a variety of socioeconomic changes. Exploring the status of
      'youth', in this context, through the prism of AIDS sheds light on how a
      pathology can reveal social change in the 'youth' category undergoing the process
      of transition to adulthood. The data for this article are drawn from an
      anthropological study carried out between 2006 and 2008 in Ouagadougou (Burkina
      Faso) based on 21 single young women (16 to 28 years old) infected with HIV. The
      data analysis highlighted issues of relationship to self (biographical disruption
      and jeopardized female identity) and to others (weakening of social ties in
      situations of dependency and of pursuit of social advancement) that arise after
      they discover their seropositive status. The different forms of vulnerability
      (identity-related, relational and situational) engendered by their status as
      seropositive women in a context of socioeconomic change, where there are a
      variety of issues at stake, raise the question of how these young women manage
      the risk of HIV transmission, and lead to a re-examination of the problem of the
      vulnerability of youth dealing with HIV.

PMID- 23549699
TI  - Vulnerabilities in mHealth implementation: a Ugandan HIV/AIDS SMS campaign.
AB  - HIV prevalence in Uganda has leveled off, however trends indicate that incidence
      is on the rise and disproportionately affects certain vulnerable groups, such as
      women. There is growing support for using mobile health (mHealth) programs to
      reach vulnerable populations. Using the Extended Technology-Community-Management
      model for mHealth, we examined a text message campaign in Arua, Uganda, that
      disseminated and measured HIV/AIDS knowledge and promoted HIV/AIDS testing at
      clinics. Empirical data from this campaign illustrated that mHealth campaigns
      need to address socio-cultural, informational, economic and individual
      vulnerabilities. We found, for example, that the interactive SMS quiz design
      motivated recipients with the correct HIV/AIDS knowledge to respond (and thus
      become eligible for free HIV screening). In doing so, however, the more
      vulnerable sections of the population, such as those with incorrect knowledge,
      were further put at risk. We discuss the programmatic implications and provide
      strategic recommendations for campaign focus, particularly to reach young women.

PMID- 23549700
TI  - Too poor to live? A case study of vulnerability and maternal mortality in Burkina
      Faso.
AB  - This paper examines the concept of vulnerability in the context of maternal
      morbidity and mortality in Burkina Faso, an impoverished country in West Africa.
      Drawing on a longitudinal cohort study into the consequences of life-threatening
      or 'near miss' obstetric complications, we provide an in-depth case study of one
      woman's experience of such morbidity and its aftermath. We follow Kalizeta's
      trajectory from her near miss and the stillbirth of her child to her death from
      pregnancy-related hypertension after a subsequent delivery less than two years
      later, in order to examine the impact of severe and persistent illness and
      catastrophic health expenditure on her health and on her family's everyday life.
      Kalizeta's case illustrates how vulnerability in health emerges and is maintained
      or exacerbated over time. Even where social arrangements are supportive,
      structural impediments, including unaffordable and inadequate healthcare, can
      severely limit individual resilience to mitigate the negative social and economic
      consequences of ill health.

PMID- 23549701
TI  - When a prevention policy leads to economic vulnerability: the case of PMTCT in
      Senegal.
AB  - When, in 2010, a new PMTCT (Prevention of Mother-to-Child Transmission) strategy
      replaced the provision of infant formula to mothers living with HIV by a
      prophylaxis based on antiretrovirals, some Senegalese couples decided to purchase
      infant formula on their own, thereby risking 'medically induced poverty'. This
      case study analyzes the emergence of a situation of economic vulnerability
      generated by a public health policy that is nevertheless globally appropriate in
      terms of accessibility and epidemiological effectiveness. Because of the gap
      between the rationales of institutions at the international and national levels
      and those of people 'on the ground', a strategy that has been defined as progress
      in terms of equity is interpreted as a regression creating inequality. This
      situation stems from several determinants analyzed in this article: rapid and
      poorly managed transition from one strategy to another, different perceptions of
      acceptable risk levels, and inadequate communication of information by care
      providers.

PMID- 23549702
TI  - 'No one knows what will happen after these five years': narratives of ART, access
      and agency in Nigeria.
AB  - Rural Nigerians pursue a range of strategies to maximize current and future
      access to HIV treatment in the context of securing livelihoods and minimizing the
      social and economic risks of stigma. This study reports on qualitative interviews
      with service providers and anti-retroviral therapy (ART) patients accessing care
      in Benue State, Nigeria, or travelling several hours to Abuja for treatment (n =
      34). Nigerians living with HIV are keenly aware of the fragility and complex
      global and local politics of funding. Their narratives of pervasive stigma,
      economic and health system barriers to access, growing fears that free ART will
      cease, and strategies to secure access to care reveal a sophisticated synthesis
      of social determinants of health and clinical care, and challenge practitioners,
      planners, and scholars to take a similarly robust and nuanced approach to
      vulnerability, access, and agency.

PMID- 23549703
TI  - Exacerbation of vulnerability in a hospital setting in Lubumbashi (Democratic
      Republic of Congo).
AB  - This article presents an ethnographic study of the pseudonymous Saint Amand
      Hospital in Lubumbashi (Democratic Republic of Congo) and of the way in which
      struggles for control of the hospital's resources contributed to shape certain
      practices that were damaging to the institution. We examine how, following the
      disengagement of both the State and a large bankrupt mining enterprise, the
      'atypical' governance of the hospital and the institutional instability it
      generated led to professional vulnerability among care providers. We also look at
      how, in turn, this situation exacerbated the vulnerability of the helpless and
      uneducated patients attending that hospital.

PMID- 23549704
TI  - What contribution have human rights approaches made to reducing AIDS-related
      vulnerability in sub-Saharan Africa? Exploring the case study of access to
      antiretrovirals.
AB  - Human rights approaches may offer powerful tools to deal with HIV and AIDS
      related vulnerabilities experienced throughout the subcontinent's endemic
      regions. This paper examines how such approaches have contributed to remediating
      health and dignity violations posed by the inaccessibility of antiretrovirals in
      the region. Increases in regional access and key changes in the causal chain of
      drug access are explored. Rights-based social campaigns that produced domestic as
      well as global shifts in related law and policy are described in the key low- and
      middle-income countries of South Africa, Brazil and Thailand. Finally, I consider
      the implications of these shifts in relation to the strengths and weaknesses of
      rights-based approaches to reducing AIDS-related vulnerability in the region,
      arguing that these experiences indicate the need for structural fixes that codify
      the right to health at domestic and international levels, so as to entrench the
      right to medicines and enable social actors and policy-makers alike to better
      meet essential health needs.

PMID- 23549705
TI  - From bulldozing to housing rights: reducing vulnerability and improving health in
      African slums.
AB  - Forced evictions heighten vulnerability among slum dwellers who already face
      multiple risks of ill health. They constitute a well-documented violation of
      economic and social rights and are reaching epidemic proportions in sub-Saharan
      Africa as economic globalization creates and strengthens incentives for forced
      evictions. We describe evictions in the slums of four African metropolitan areas:
      Accra (Ghana), Lagos (Nigeria), Luanda (Angola) and Nairobi (Kenya). We survey
      diverse strategies used in responding to forced evictions and outline the
      challenges and barriers encountered. We conclude that the international human
      rights framework offers an important approach for protecting the health of
      vulnerable populations.

PMID- 23549706
TI  - Evaluation of a knowledge transfer strategy from a user fee exemption program for
      vulnerable populations in Burkina Faso.
AB  - As part of this special issue contributing to the development of knowledge on
      vulnerability and health in Africa, this article analyzes one example of a
      knowledge transfer strategy aimed at improving the use of research results that
      could help reduce the vulnerability of certain populations. In this case, since
      September 2008, the Non-Governmental Organization (NGO) Hilfe zur Selbsthilfe
      e.V. (HELP) has conducted a trial of subsidizing 100% of the costs of health care
      for vulnerable populations in two health districts of Burkina Faso. A scientific
      partnership was created to produce evidence on the intervention, and a knowledge
      transfer strategy was developed to promote the use of that evidence by
      stakeholders (decision-makers, people working in the health system, funding
      partners, etc.). The results showed that considerable efforts were invested in
      knowledge transfer activities and that these led to all types of use
      (instrumental, conceptual, persuasive). However, considerable variation in use
      was observed from one setting to another. This article presents some lessons to
      be drawn from this experience.

PMID- 23549709
TI  - Amidine functionality as a stimulus-responsive building block.
AB  - This mini-review describes basic features and applications of small molecules and
      macromolecules containing amidine, and to a lesser extent, guanidine functional
      groups. The emphasis in this article is on the exploitation of such functionality
      as species that are capable of reversibly binding carbon dioxide in the presence
      of water, a process that also commonly involves a hydrophobic-to-hydrophilic
      transition. The review is not intended to be exhaustive but rather serves to
      highlight this one particular feature and demonstrate its application in areas
      ranging from reversible emulsion stabilization, purification and reversible self
      assembly of polymeric nanoparticles. 

PMID- 23549710
TI  - Confronting a "big huge gaping wound": emotion and anxiety in a cultural
      sensitivity course for psychiatry residents.
AB  - In his seminal volume From anxiety to method in the behavioral sciences, George
      Devereux suggests that any therapeutic or scientific engagement with another
      human being inevitably will be shaped by one's own expectations, assumptions, and
      reactions. If left unacknowledged, such unspoken and unconscious influences have
      the capacity to torpedo the interaction; if subjected to critical reflection,
      however, they can yield insights of great interpretive value and practical
      significance. Taking these reflections on counter-transference as point of
      departure, this article explores how a range of unacknowledged assumptions can
      torpedo good faith efforts to engender "cultural sensitivity" in a required
      course for American psychiatry residents. The course examined in this paper has
      been taught for seven successive years by a pair of attending psychiatrists at a
      longstanding New England residency training program. Despite the instructors'
      good intentions and ongoing experimentation with content and format, the course
      has failed repeatedly to meet either residents' expectations or, as the
      instructors bravely acknowledged, their own. The paper draws upon a year-long
      ethnographic study, conducted in the late 2000s during the most recent iteration
      of the course, which involved observation of course sessions, a series of
      interviews with course instructors, and pre- and post-course interviews with the
      majority of participating residents. By examining the dynamics of the course from
      the perspectives of both clinician-instructors and resident-students, the paper
      illuminates how classroom-based engagement with the clinical implications of
      culture and difference can run awry when the emotional potency of these issues is
      not adequately taken into account.

PMID- 23549711
TI  - A diversity of voices: the McGill 'Working with Culture' seminars.
AB  - The Working with Culture seminar is offered as a course during the month long
      Annual McGill Summer Program for Social and Transcultural Psychiatry, attended by
      local and international participants each May since 1994. The article outlines
      some of the premises and pedagogical approaches of this clinically oriented
      biweekly seminar series with discussions and didactic teaching on cultural
      dimensions of mental health care. The course readings, seminar topics and invited
      speakers focus mainly on therapist client encounters constructed by the multiple
      voices with dimensions of psychiatric, social, historical, legal, ethical,
      political, systemic and intra-psychic domains. The dual leadership emphasizes the
      gaps and complementarity amongst voices, and it invites and supports a
      destabilizing decentering process and the creation of solidarities amongst
      participants. Applying a bio-psychosocial case study method, each 3-h seminar
      engages the participants in a critical dialogue on apprehending the enmeshment of
      social suffering with psychiatric disorders whilst examining the usefulness and
      the limits of cultural formulation models. The seminar working group and teaching
      approach acknowledges cultural hybridity as a dynamic process marked by
      continuous therapist attunement to uncertainty or 'not knowing' which implies a
      dethroning of an expert position.

PMID- 23549712
TI  - Functional task kinematics of the thumb carpometacarpal joint.
AB  - BACKGROUND: Abnormal biomechanical loading has been identified as an associated
      risk factor of osteoarthritis in the wrist and hand. Empirical data to date are
      insufficient to describe the role of altered biomechanics in thumb
      carpometacarpal (CMC) arthritis. QUESTIONS/PURPOSES: This is a pilot study to
      evaluate motion analysis of the upper extremity while performing functional
      tasks. We wished to describe the in vivo kinematics of the thumb and hand in
      relation to the larger joints of the upper extremity in subjects without
      arthritis in functional positions at rest and while loading the CMC joint. If
      reproducible, we then planned to compare kinematics between these subjects and a
      subject with advanced thumb CMC arthritis. METHODS: In vivo kinematics of the
      hand and upper extremity during the functional tasks of grasp, jar opening, and
      pinch with and without loading of the CMC joint were evaluated using cameras and
      a motion-capture system in four asymptomatic female subjects and one female
      subject with advanced radiographic (Eaton Stage IV) osteoarthritis. RESULTS:
      Kinematics of the hand and upper extremity can be reliably quantified. Loading of
      the CMC joint did not alter the hand and forearm kinematics in control subjects.
      In the subject with osteoarthritis, the adduction-extension deformity at the CMC
      joint resulted in kinematic alterations as compared with the four control
      subjects. CONCLUSIONS: This study represents preliminary steps in defining thumb
      CMC position, motion, and loading associated with activities of daily living.
      These findings enhance our understanding of motion at the CMC joint and how it
      differs in arthritic patients. LEVEL OF EVIDENCE: Level II, prognostic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 23549713
TI  - Reinforcement of closure of stoma site using a biological mesh.
AB  - Incisional hernia at the site of stoma closure is an under-reported problem,
      having been recently shown to occur in up to 30 % of patients. This technical
      note describes a technique for the placement of intraperitoneal biological mesh
      to prophylactically reinforce stoma closure sites. Seven consecutive patients
      underwent mesh placement as part of a pilot study. Following closure of the stoma
      through a trephine incision, 6 anchoring sutures were placed between the
      peritoneum/deep fascia and the edges of the mesh circumferentially. The mesh was
      delivered into the peritoneal cavity and parachuted up against the abdominal
      wall, and the sutures tied. If closure was performed through a midline
      laparotomy, the anchoring sutures were placed in a similar fashion through the
      midline incision. The fascia above the mesh and soft tissues was then closed. The
      mesh was successfully placed in all 7 patients. Follow-up at 30 days showed one
      superficial wound infection. An ultrasound scan of this patient revealed that the
      mesh was still in place and that the infection did not breach the fascia. No
      other early adverse events occurred. Prophylactic biological mesh reinforcement
      of stoma closure sites is technically feasible and safe in the short term. Longer
      term results from a prospective randomised trial are needed, including clinical
      and radiological assessment for hernia rates, to establish what if any are the
      realisable benefits of this technique. 

PMID- 23549714
TI  - Human papillomavirus detected in a colonic metastasis of cervical adenocarcinoma.

PMID- 23549715
TI  - Clinical research with traditional herbal medicines.

PMID- 23549716
TI  - Geographical distribution of chronic kidney disease of unknown origin in North
      Central Region of Sri Lanka.
AB  - OBJECTIVES: In early nineties investigators noticed an alarmingly high incidence
      of an apparently new form of chronic kidney disease of unknown aetiology (CKD-U)
      in some parts of Sri Lanka. The aim of the study was to investigate the
      geographical distribution of CKD-U using GIS and GPS mapping. METHODS: Community
      based information was collected from 11,630 patients for GIS mapping using ARC
      9.2 software. Based on GIS mapping, two locations were selected for GPS mapping
      to locate the households of 863 CKD-U patients with reference to reservoirs,
      irrigation canals and the topography of the areas. RESULTS: GIS mapping indicated
      five high prevalence areas of CKD-U. Communities who consumed water from natural
      springs showed a low prevalence of the disease. GPS mapping showed that most of
      the affected villages were located below the reservoirs and canals with stagnant
      irrigated water. CONCLUSION: Epidemiological data on geographical distribution
      infers that while older foci of CKD-U are persisting, there is an emergence of
      new foci with time. The location of the affected villages below the level of the
      reservoirs/canals may indicate the possibility of draining of irrigated water to
      the shallow wells of the households, which is the source of drinking water.

PMID- 23549717
TI  - Trends and determinants of childhood stunting and underweight in Sri Lanka.
AB  - INTRODUCTION: Child undernutrition is a major risk factor for child mortality and
      adult ill-health. Despite substantial progress in most health indicators,
      undernutrition remains high in Sri Lanka, with recent trends being unclear, owing
      to methodological differences in national surveys. METHODS: This study uses data
      from the 1987, 1993, 2000 and 2006-07 Demographic and Health Surveys (DHS) and
      the 2009 Nutrition and Food Security Survey (NFSS) to investigate trends and
      determinants of child undernutrition in Sri Lanka. The prevalence rates of
      stunting, underweight and wasting were re-estimated using the 2006 WHO growth
      standards to ensure consistency. Multivariate regression analysis was then
      undertaken to analyse the determinants of height-forage in children aged 9-23
      months, and 24-59 months, and the relative impact of key factors was assessed
      using prediction models. RESULTS: Stunting and wasting substantially improved
      from 1987 to 2000, but rates stagnated from 2000 to 2006/07. Whilst economic
      inequalities in under nutrition were greater than in most other countries, the
      multivariate analysis found that maternal height, household wealth, length of
      breast-feeding and altitude are significant determinants of stunting, but
      differences in child feeding practices and other factors were not. Of these,
      maternal height and household wealth had the most influence. CONCLUSION: The
      results are consistent with the finding that food insecurity is the main driver
      of undernutrition, but more research is required to validate this. The strong
      relationship of child height with maternal height suggests that epigenetic
      factors, proxied by short maternal height, constrain the applicability of the WHO
      growth standards in Sri Lanka.

PMID- 23549718
TI  - Obstetric performance of women who have previously delivered a baby of low
      birthweight.
AB  - OBJECTIVES: To investigate pregnancy outcomes in women who have previously given
      birth to a baby weighing less than 2500 grams in a population in which the low
      birthweight rate is high. METHODS: We compared the obstetric performance of 100
      women who had delivered a low birthweight baby (<2500g) at term in a previous
      pregnancy (cases) with those of 100 women who were matched for age, height, body
      mass index at booking, parity and medical disorders, who had previously delivered
      a baby above that threshold (controls). RESULTS: We found the following
      significant differences between cases and controls (p<0.001 for all). Gestation
      at delivery (mean+/-SD = 38.0+/-1.9 vs. 39.1 +/- 1.2 weeks); risk of delivery
      before completion of 37 weeks (19.0% vs. 3.0%); birthweight (mean+/-SD = 2.553 +/
      0.444 vs. 3.015 +/- 0.413 Kg); risk of delivery of a low birthweight (LBW) baby
      in the current pregnancy (27.0% vs. 4.0%). The stillbirth rate was also
      significantly higher among cases (4 vs. 0; p<0.05). CONCLUSIONS: Birth of a LBW
      baby points to adverse events in future pregnancies even where its prevalence is
      high. It is a useful criterion for assessment of risk in antenatal care and for
      directed interventions.

PMID- 23549719
TI  - Tuberculous meningitis in adults: a prospective study at a tertiary referral
      centre in Sri Lanka.
AB  - INTRODUCTION: Central nervous system tuberculosis is the most severe form of
      extrapulmonary TB and it is associated with a substantial morbidity and
      mortality. OBJECTIVES: To describe the demographic profile, clinical features,
      laboratory and imaging results of a cohort of adult patients with TBM
      (Tuberculous meningitis). METHODS: This study encompasses a prospective analysis
      of all adult cases of TBM diagnosed from 1st January 2010 to 31st December 2011
      in the Neurology unit 2, National Hospital of Sri Lanka. Consensus case
      definitions for TBM were used for clinical case classification and patients were
      given a definite, probable, or possible tuberculous meningitis status
      accordingly. RESULTS: A total of 89 patients fulfilled the established diagnostic
      criteria for TBM and there were 22 definitive cases, 46 probable cases and 21
      possible cases. The mean age of the series was 44 years and 56 (63%) were males.
      TBM presented with fever in 64 (71%), general constitutional symptoms in 61
      (68%), headache in 53 (59%), and diminished level of consciousness in 36 (40%)
      patients. CSF biochemistry revealed elevated protein in all patients. MRI brain
      showed meningeal enhancement in 73 (82%). Twenty four (27%) died during
      hospitalisation and out of 65 who survived 44 (49%) had residual sequelae at the
      time of discharge. CONCLUSIONS: MRI evidence and biochemical analysis of CSF are
      still the main supportive diagnostic modalities. TBM is a relatively common but
      difficult to diagnose disease, which results in significant morbidity and
      mortality.

PMID- 23549720
TI  - Clinical profile and difficulties in diagnosis of central nervous system
      infections in adult patients in a tertiary care hospital.
AB  - OBJECTIVES: We aimed to describe the pattern of central nervous system (CNS)
      infections and accuracy of diagnosis in a Sri Lankan tertiary care hospital.
      METHODS: We prospectively studied all adult patients with suspected CNS infection
      admitted over a two-year period. Data were collected on demographic and clinical
      features, laboratory findings, treatment and immediate outcome. Diagnosis of CNS
      infection was categorized as definite, probable, possible and uncertain. RESULTS:
      We studied 215 patients [59.1% males; mean age (SD) 44 (20) years]. Blood
      cultures were done in 65 (30.2%) and only one was positive. Lumbar puncture was
      done in 146 (67.9%), and cerebrospinal fluid Gram stains, culture and acid-fast
      bacilli stains were all negative. Diagnosis of CNS infection was considered
      'definite' in only one patient, 'probable' in 57.2%, 'possible' in 5.6%, and
      'uncertain' in 26%. An alternative diagnosis was found in 23 patients (10.7%).
      Intravenous antibiotics and aciclovir were given on emperical grounds, largely
      without microbiological confirmation. CONCLUSIONS: Diagnosis of CNS infections is
      highly unsatisfactory with available facilities, even in a tertiary care setting.

PMID- 23549721
TI  - Respiratory illnesses and ventilatory function among gem cutters in Sri Lanka.
AB  - INTRODUCTION: This study explores the proportion of respiratory symptoms and
      ventilatory functions among gem cutters in the city of gems, in Sri Lanka.
      METHODS: All gem cutters in the Ratnapura Medical Officers of Health area were
      included and the control group was selected from the government officers residing
      in the same area. The gem cutters and the controls were matched according to
      their age and sex. Pulmonary function was measured with a spirometer and peak
      flow meter. RESULTS: A significantly higher percentage of the exposed workers
      reported recurrent and prolonged cough (35%) and chest tightening (10%). FEV1 and
      FEV1/FVC was significantly lower in the exposed workers compared with unexposed
      workers. The results remained the same for the FEV1/FVC ratio (p=0.004) after
      adjusting for age and body mass index. CONCLUSIONS: Adverse respiratory health
      effects observed among gem cutters were probably caused by exposure to gem dust.

PMID- 23549722
TI  - Kikuchi-Fujimoto's disease: a case series from Sri Lanka.
AB  - INTRODUCTION: Kikuchi's disease is a rare, benign, self-limiting disease, mainly
      involving the lymph nodes of young people. The etiology is unknown. Clinical
      symptoms and basic investigations may mimic lymphomas and chronic granulomatous
      conditions like tuberculosis. Lymph node biopsy shows characteristic diagnostic
      features. Even though described internationally, the local disease pattern or
      incidence has not been well studied. METHODS: We studied all patients who were
      diagnosed with Kikuchi's disease at Teaching Hospital, Peradeniya from January
      2011 to April 2012. RESULTS: A total of 9 cases showed histopathological features
      of Kikuchi's disease. All patients were females, in the age group of 12-30 years
      having fever and lymphadenopathy. They carried a provisional diagnosis of
      lymphoma, tuberculosis or reactive lymphadenitis. CONCLUSIONS: Necrotising
      lymphadenitis has a predilection for cervical lymph nodes of females and is
      usually accompanied by fever. Clinical features can resemble tuberculous
      lymphadenitis or malignant lymphoma. Excision biopsy of the involved node is
      mandatory for the diagnosis.

PMID- 23549723
TI  - A rare cause of acute abdomen: torsion of a second spleen.

PMID- 23549724
TI  - Isolation of Neisseria meningitidis from cadaveric blood.

PMID- 23549725
TI  - Multiple subcutaneous folds in oculocerebrorenal syndrome of Lowe.

PMID- 23549726
TI  - Double inferior vena cava: beware!

PMID- 23549727
TI  - Soto syndrome: a rare overgrowth disorder.

PMID- 23549728
TI  - IPEX syndrome with membrano-proliferative nephrotic syndrome.

PMID- 23549729
TI  - Current perspectives on the intensity of natural selection of MHC loci.
AB  - Polymorphism of genes in the major histocompatibility complex (MHC) is believed
      to be maintained by balancing selection. However, direct evidence of selection
      has proven difficult to demonstrate. In 1994, Satta and colleagues estimated the
      selection intensity of the human MHC (human leukocyte antigen (HLA)) loci;
      however, at that time the number of HLA sequences was limited. By comparing five
      different methods, this study demonstrated the best way to calculate the
      selection coefficient, through a computer simulation study. Since the study, many
      HLA nucleotide sequences have been made available. Our new analysis takes
      advantage of these newly available sequences and compares new estimates with
      those of the previous study. Generally, our new results are consistent with those
      of the 1994 study. Our results show that, even after 20 years of exhaustive
      sequencing of human HLA, the number of dominant HLA alleles, on which our
      original estimate of selection intensity depended, appears to be conserved.
      Indeed, according to the frequency distribution for each HLA allele, most
      sequences in the database were minor or private alleles; therefore, we conclude
      that the selection intensities of HLA loci are at most 4.4 % even though the HLA
      is the prominent example on which the natural selection has been operating.

PMID- 23549730
TI  - Distribution of MICB diversity in the Zhejiang Han population: PCR sequence-based
      typing for exons 2-6 and identification of five novel MICB alleles.
AB  - The polymorphism of major histocompatibility complex class I chain-related gene B
      (MICB) and variations in MICB alleles in a variety of populations have been
      characterized using several genotyping approaches. In the present study, a novel
      polymerase chain reaction sequence-based typing (PCR-SBT) method was established
      for the genotyping of MICB exons 2-6, and the allelic frequency of MICB in the
      Zhejiang Han population was investigated. Among 400 unrelated healthy Han
      individuals from Zhejiang Province, China, a total of 20 MICB alleles were
      identified, of which MICB*005:02:01, MICB*002:01:01, and MICB*004:01:01 were the
      most predominant alleles, with frequencies of 0.57375, 0.1225, and 0.08375,
      respectively. Nine MICB alleles were detected on only one occasion, giving a
      frequency of 0.00125. Of the 118 distinct MICB ~ HLA-B haplotypes identified, 42
      showed significant linkage disequilibrium (P < 0.05). Haplotypes MICB*005:02:01 ~
      B*46:01, MICB*005:02:01 ~ B*40:01, and MICB*008 ~ B*58:01 were the most common
      haplotypes, with frequencies of 0.0978, 0.0761, and 0.0616, respectively. Five
      novel alleles, MICB*005:07, MICB*005:08, MICB*027, MICB*028, and MICB*029 were
      identified. Compared with the MICB*005:02:01 sequence, a G > A substitution was
      observed at nucleotide position 210 in MICB*005:07, and a 1,134 T > C
      substitution in MICB*005:08 and an 862 G > A substitution in MICB*027 were
      detected. In addition, it appears that MICB*028 probably arose from
      MICB*004:01:01 with an A to G substitution at position 1,147 in exon 6. MICB*029
      had a G > T transversion at nucleotide position 730 in exon 4, compared with that
      of MICB*002:01:01. On the basis of the new PCR-SBT assay, these observed results
      demonstrated MICB allelic variations in the Zhejiang Han population.

PMID- 23549731
TI  - [Ability of smell after medialization of the middle nasal turbinate in endoscopic
      sinus surgery].
AB  - BACKGROUND: Endoscopic sinus surgery usually requires a move of the middle nasal
      turbinate into the midline to achieve a better sight into the ethmoidal sinuses.
      In this procedure damages of the turbinate are possible, which later can lead to
      a scarred fixation of the turbinate. Fixing of the turbinate to the septum can
      avoid this effect, but could reduce smell ability by blocking of the upper nasal
      duct. MATERIAL: In a prospective study with 83 patients with chronic sinusitis
      (55% CRS with polyps, 45% CRS without polyps) at the end of the operation the
      middle nasal turbinates were fixed at the nasal septum with a 4 * 0 stitch.
      Before the operation and 6 weeks, 3 and 5 months after operation the smell was
      tested using the "sniffin'sticks" threshold test. RESULTS: After operation the
      ethmoidal area remained open without developing of relevant synechiae or scars.
      The smell ability decreased after surgery due to the obstruction of the upper
      nasal duct, but improved again later. After 5 months the average threshold of
      smell was better than before operation. Testing of the threshold values with the
      t-test showed a significant difference (p<0.001) between the pre- and
      postoperative status. CONCLUSION: The method of medialization and temporary
      septal fixation of the middle nasal turbinate allows a sufficient ventilation and
      drainage of the paranasal sinuses after sinus surgery. Due to only temporary
      fixation of the turbinate at the septum, a permanent obstruction of the upper
      nasal duct and the olfactory area is prevented. Thus the threshold of smell is
      not reduced.

PMID- 23549733
TI  - Mechanisms of metal-catalyzed dehydrocoupling reactions.
AB  - This review summarizes selected mechanistic insight garnered from reactions that
      form bonds between main group elements with liberation of hydrogen,
      dehydrocoupling or dehydropolymerization reactions. Focus has been made where
      mechanistic study has been done or provides unique insight as compared to
      previous work. Thus, a limited number of catalysts and substrates will be
      discussed, but a broad range of mechanistic features will be noted. A comparative
      approach considering dehydrocoupling reactions that appear to proceed by certain
      mechanistic steps is taken here, beginning with steps that are well established
      and general then moving to those that are newer, at least to this application.

PMID- 23549732
TI  - Complete pathological response is predictive for clinical outcome after tri
      modality therapy for carcinomas of the superior pulmonary sulcus.
AB  - The objective was to define the relationship between histopathological changes
      after pre-operative chemo-radiotherapy (CRT) and clinical outcome following tri
      modality therapy in patients with superior sulcus tumours. A retrospective
      analysis of tumour material was performed in a series of 46 patients who received
      tri-modality therapy between 1997 and 2007. Median follow-up was 34 months (5
      154). Pathological complete response (pCR) was present in 20/46 tumours (43 %).
      The most common RECIST score after CRT in patients with pCR was a partial
      response (PR; 10/17, three unknown), whereas in patients without a pCR, stable
      disease was the most common (22/26) (p = 0.002). In 26 specimens with residual
      tumour, this was mainly located in the periphery of the lesion rather than the
      centre (Spearman's correlation = 0.67, p < 0.001). Prognosis was significantly
      better after a pCR compared to residual tumour (70 % 5-year overall survival vs.
      20 %; p = 0.001) and in patients with fewer than 10 % vital tumour cells as
      compared to those with >10 % (65 % 5-year overall survival vs. 18 %; p < 0.001).
      A low mitotic count was associated with a longer disease-free survival (p =
      0.02). Complete pathological response and the presence of fewer than 10 % vital
      tumour cells after pre-operative CRT are both associated with a more favourable
      prognosis. A modification of the pathological staging system after radiotherapy,
      incorporating the percentage of vital tumour cells, is proposed.

PMID- 23549734
TI  - Regional characteristics of histamine uptake into neonatal rat astrocytes.
AB  - Histaminergic signalling constitutes an attractive target for treatment of
      neuropsychiatric disorders. One obstacle to developing new pharmacological
      options has been failure to identify putative specific histamine transporter
      responsible for histamine clearance. Although high-affinity histamine uptake was
      detected in neonatal cortical astrocytes, its existence in other brain regions
      remains largely unexplored. We investigated whether cerebellar and striatal
      astrocytes participate in histamine clearance and evaluated the role of organic
      cation transporters (OCT) in astroglial histamine transport. Kinetic and
      pharmacological characteristics of histamine transport were determined in
      cultured astrocytes derived from neonatal rat cerebellum, striatum and cerebral
      cortex. As well as astrocytes of cortical origin, cultured striatal and
      cerebellar astrocytes displayed temperature-sensitive, high-affinity histamine
      uptake. Exposure to ouabain or Na(+)-free medium, supplemented with choline
      chloride markedly depressed histamine transport in cortical astrocytes.
      Conversely, histamine uptake in striatal and cortical astrocytes was ouabain
      resistant and was only partially diminished during incubation in the absence of
      Na(+). Also, histamine uptake remained unaltered upon exposure to OCT inhibitor
      corticosterone, although OCTs were expressed in cultured astrocytes. Finally,
      histamine transport in cerebellar and striatal astrocytes was not sensitive to
      antidepressants. Despite common characteristics, cerebellar astrocytes had lower
      affinity, but markedly higher transport capacity for histamine compared to
      striatal astrocytes. Collectively, we provide evidence to suggest that
      cerebellar, striatal as well as cortical astrocytes possess saturable histamine
      uptake systems, which are not operated by OCTs. In addition, our data indicate
      that Na(+)-independent histamine carrier predominates in cerebellar and striatal
      astrocytes, whereas Na(+)-dependent transporter underlies histamine uptake in
      cortical astrocytes. Our findings implicate a role for histamine transporters in
      regulation of extracellular histamine concentration in cerebellum and striatum.
      Inhibition of histamine uptake might represent a viable option to modulate
      histaminergic neurotransmission.

PMID- 23549735
TI  - Effect of brominated furanones on the formation of biofilm by Escherichia coli on
      polyvinyl chloride materials.
AB  - To study the influence of brominated furanones on the biofilm (BF) formation by
      Escherichia coli (E. coli) on polyvinyl chloride (PVC) material, and to provide
      new ways of surface modification of materials to clinically prevent biomaterial
      centered infection. Three brominated furanones, dissolved in ethanol, furanone
      1(3,4-dibromo-5-hydroxyl-furanone), furanone-2(4-bromo-5-(4-methoxypheny)-3
      (methylamino)-furanone), and furanone-3(3,4-dibromo-5,5-dimethoxypheny-2(5H)
      furanone) with representative chemical structure, were coated on the surfaces of
      separate PVC materials (1 * 1 cm), respectively. The surface-modified PVC
      materials were incubated with E. coli and for controls, 75 % ethanol-treated PVC
      materials were used. This treatment played as control group. The cultivation
      incubations were for 6, 12, 18, and 24 h. The thickness of bacterial BF and
      bacterial community quantity unit area on the PVC materials was determined by
      confocal laser scanning microscopy (CLSM), and the surface structure of bacterial
      BF formation was examined by scanning electron microscopy (SEM). The results of
      CLSM indicated the thickness of bacterial BF and bacterial community quantity
      unit area on PVC materials treated with furanone-3 were significantly lower than
      that of control at all time points (P < 0.05), whereas, the differences between
      furanone-1 and furanone-2 groups and control group were not significantly
      different (P > 0.05). The results of SEM indicated that after 6 h incubation, the
      quantity of bacterial attachment to the surface of PVC material treated with
      furanone-3 was lower than the control group. By 18 h incubation there was
      completely formed BF structure on the surface of control PVC material. However,
      there was no significant BF formation on the surface of PVC material treated with
      furanone-3. The impact of different brominated furanones on SA biofilm formation
      on the surface of PVC materials are different, furanone-3 can inhibit E. coli
      biofilm formation on the surface of PVC material.

PMID- 23549736
TI  - Association of the SNP rs1800925(C/T) in the interleukin-13 gene promoter with
      pulmonary function in Chinese Han patients with idiopathic pulmonary fibrosis.
AB  - The present report studied potential association of the rs1800925(C/T) single
      nucleotide polymorphism (SNP) of the Interleukin (IL)-13 gene promoter with
      idiopathic pulmonary fibrosis (IPF) in patients of Chinese Han ethnicity. Seventy
      patients with IPF were enrolled and divided into three subgroups: group A (61-79
      % pred. DLCO; n = 22), group B (51-60% pred. DLCO; n = 20), and group C (<=50%
      pred. DLCO; n = 28). Control group consisted of 80 healthy individuals of Chinese
      Han ethnicity. The SNP rs1800925(C/T) was genotyped by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis. The IL-13 CC
      genotype was present in 28/70 (40.0%), homozygous TT in 6/70 (8.6%) and
      heterozygous CT in 36/70 (51.4%) patients with IPF. In control group, these
      genotypes were present in 30/80 (37.5%), 11/80 (13.75%), 39/80 (48.75%),
      respectively, indicating that the distribution of the above three genotypes was
      not significantly different between patients with IPF and healthy controls. When
      the patients were stratified according to their DLCO and DLCO/VA, the frequencies
      of genotypes CT and TT in the groups A, B, and C were, respectively, 40.9%
      (9/22), 50% (10/20), and 82.1% (23/28). Thus, significant differences in the
      distribution of alleles at -1112 region of IL-13 gene were observed among the
      study groups A, B, and C, with the highest frequency in group C (p < 0.05). In
      conclusion, the rs1800925 T allele of the IL-13 gene is associated with worse
      pulmonary function in patients with IPF of Chinese Han ethnicity.

PMID- 23549737
TI  - Pulmonary artery reconstruction using autologous pericardium or azygos venae
      substitute for surgical treatment of central non-small cell lung cancer.
AB  - We evaluated the clinico-surgical significance of pulmonary artery (PA)
      reconstruction using a patch of autologous pericardium/azygos venae substitute to
      treat central non-small cell lung cancer in 62 patients with pulmonary arteries
      invaded by tumor. According to TNM-classification, four patients were stage IIb,
      46 were stage IIIa, and 12 were stage IIIb. Depending on tumor infiltration,
      surgical procedures included partial PA tangential resections/reconstructions by
      a patch of autologous azygos venae, a patch of autologous pericardium and
      complete PA sleeve resection and reconstruction by a custom-made autologous
      pericardial conduit interposition. 47 patients received postoperative
      chemotherapy and 19 received radiotherapy. There were 2 (3.2%) postoperative
      early deaths due to bronchial anastomotic leakage. Postoperative complications
      occurred in 17.7% (11/62) patients and all recovered uneventfully. Mean follow-up
      time after surgical resection was 49.5 (6-12) months and overall <=1-, 3-, 5-,
      and >=10-year survival rates were 80.2, 44.7, 31.4, and 23.1%, respectively. It
      was concluded that autologous pericardial patch and azygos vein patch
      reconstruction of PA were safe and effective. Regarding extended circumferential
      defects after sleeve resection in which end-to-end anastomosis is not feasible,
      autologous pericardial conduit interposition may be useful for reconstruction
      when a tumor extensively infiltrates full circumference of the PA.

PMID- 23549738
TI  - Minimal biofilm eradication concentration of antimicrobial agents against
      nontypeable Haemophilus influenzae isolated from middle ear fluids of intractable
      acute otitis media.
AB  - Nontypeable Haemophilus influenzae (NTHi) makes the clinical course of acute
      otitis media (AOM) intractable by forming a biofilm that may hamper the clearance
      of the bacteria from middle ear cavity. In this study, we evaluated the minimum
      biofilm eradication concentration (MBEC) of antimicrobial agents against biofilm
      forming NTHi strains. Twelve NTHi strains isolated from middle ear fluids of
      Japanese children with intractable AOM before antimicrobial treatment were
      evaluated for MBEC of fluoroquinolones in comparison with those of beta-lactams
      and macrolides. AMPC and CDTR required much higher concentration, i.e., high
      MBECs, to suppress the biofilm formation of NTHi. In contrast, fluoroquinolones
      followed by macrolides showed lower MBECs. MBEC would be a good parameter to
      infer the efficacies of antimicrobials against NTHi in biofilm.

PMID- 23549740
TI  - Lipopeptides rather than lipopolysaccharide favor the development of dendritic
      cell dysfunction similar to polymicrobial sepsis in mice.
AB  - OBJECTIVE: We investigated whether the dysfunction of dendritic cells (DC) that
      develops during polymicrobial sepsis is mimicked by systemic administration of
      the Toll-like receptor (TLR) 4 agonist lipopolysaccharide (LPS) or of the TLR2
      agonist Pam3-Cys-Ser-Lys4 (P3CSK4). MATERIALS AND METHODS: BALB/c mice underwent
      cecal ligation and puncture (CLP) or sham operation or received a single i.p.
      injection of LPS (30 mg/kg body weight), P3CSK4 (10 mg/kg body weight), or saline
      as control. Purified splenic DC and in-vitro-generated DC from bone marrow were
      analyzed in terms of surface marker expression, cytokine secretion, and antigen
      specific T-cell activation in vivo. RESULTS: Splenic DC were suppressed in IL-12
      secretion 12 h after LPS and P3CSK4 administration but released increased levels
      of IL-12 4 days after TLR agonist application, unlike DC from CLP mice.
      Polymicrobial sepsis and TLR agonists caused a loss of DC in the spleen but led
      to the expansion of diverse DC subsets. DC that differentiated from bone marrow
      after P3CSK4 but not after LPS application resembled DC from CLP mice regarding
      cytokine secretion and impaired Th1-cell polarization. CONCLUSIONS: The
      development of DC dysfunction during sepsis is at least partly mimicked by TLR2
      agonists rather than TLR4 agonists.

PMID- 23549742
TI  - [Is "place and train" the Right Way?].

PMID- 23549743
TI  - [Employability as a problem of the vocational rehabilitation of the disabled].

PMID- 23549741
TI  - Polymorphonuclear neutrophils and instability of the atherosclerotic plaque: a
      causative role?
AB  - OBJECTIVE: The aim of this review is to examine the role of polymorphonuclear
      neutrophils (PMNs) in the evolution of atherosclerosis. INTRODUCTION: While the
      role of PMNs in the evolution of atherosclerosic process has failed until
      recently to attract much attention, a body of research carried out over the last
      decade has disclosed the unexpectedly complex behavior of these cells, unraveling
      an unexpected key role for PMNs in the onset and progression of atheroma.
      METHODS: A PubMed database search was performed for studies providing evidences
      on the role of PMNs in the development and progression of atherosclerotic lesion.
      RESULTS AND CONCLUSIONS: Activated PMNs were shown to produce and release
      reactive oxygen species, inflammatory leukotrienes and proteolytic lysosomal
      enzymes, directly inducing vascular damage. Activated PMNs also secrete
      myeloperoxidase, involved in lipoprotein oxidation. PMNs have a finite lifespan
      and typically die through apoptosis, which thus represents a counter-regulatory
      mechanism limiting the toxic potential of these short-lived, terminally
      differentiated cells. Dysregulation of this process probably contributes to the
      pathogenesis and progression of several inflammatory diseases. Moreover, high
      circulating levels of PMN-platelet aggregates have been reported in patients with
      clinical atherosclerosis, and recent studies suggest that these aggregates may
      play a role in vascular response to injury. It has been suggested that this
      heterotypic interaction between platelets and leukocytes might represent a link
      between hemostasis/thrombosis and the inflammatory response.

PMID- 23549744
TI  - Molecular cloning and characterization of active truncated dextransucrase from
      Leuconostoc mesenteroides B-1299CB4.
AB  - The open reading frame of dsrE563, a dextransucrase gene obtained from a
      constitutive mutant (CB4-BF563) of Leuconostoc mesenteroides B-1299, consists of
      8,511 bp encoding 2,836 amino acid residues. DsrE563 contains two catalytic
      domains (CD1 and CD2). Two truncated derivative mutants DsrE563DeltaCD2DeltaGBD
      (DsrE563-1) and DsrE563DeltaCD2DeltaVR (DsrE563-2) of DsrE563 were constructed
      and expressed using the pRSETC vector in Escherichia coli. The derivatives
      DsrE563-1 (deletion of 1,620 amino acids from the C-terminus) and DsrE563-2
      (deletion of 1,258 amino acids from the C-terminus and 349 amino acids from the N
      terminus) were expressed as active enzymes. Both enzymes synthesized less-soluble
      dextran, mainly containing alpha-1,6 glucosidic linkage. The synthesized less
      soluble dextran also had a branched alpha-1,3 linkage. DsrE563-2 showed 4.5-fold
      higher dextransucrase activity than that of DsrE563-1 and showed higher acceptor
      reaction efficiency than that of dextransucrase from L. mesenteroides 512 FMCM
      when various mono or disaccharides were used as acceptors. Thus, the glucan
      binding domain was important for both enzyme expression and dextransucrase
      activity.

PMID- 23549745
TI  - Development of biological soil disinfestations in Japan.
AB  - Biological soil disinfestations (BSDs) were developed separately in Japan and in
      The Netherlands as an alternative to chemical fumigations. In Japan, it was
      developed based on the knowledge of irrigated paddy rice and upland crop rotation
      system that was rather tolerant of soil-borne disease development. The methods
      consist of application of easily decomposable organic matter, irrigation, and
      covering the soil surface with plastic film, thereby inducing anaerobic
      (reductive) soil conditions and suppressing many soil-borne pests including
      fungi, bacteria, nematodes, and weeds. The methods are widely used by organic
      farmers in the area where residences and agricultural fields are intermingled. To
      note one advantage of these methods, maintenance of soil suppressiveness to
      Fusarium wilt of tomato was suggested, while soil treated with chloropicrin
      became conducive to the disease. Suppression of soil-borne fungal pathogens by
      BSDs might be attributed to anaerobicity and high temperature, organic acids
      generated, and metal ions released into soil water. Contributions of respective
      factors to suppression of respective pathogens might be diverse. Presumably,
      these factors might vary on the fungal community structure in BSD-treated soil.
      These factors also work in paddy fields. Therefore, the BSDs developed in Japan
      are probably a method to raise the efficacy of paddy-upland rotation through
      intensive organic matter application and through maintenance of a strongly
      anaerobic (reductive) soil condition.

PMID- 23549746
TI  - Characteristics and activity analysis of epothilone operon promoters from
      Sorangium cellulosum strains in Escherichia coli.
AB  - The epothilones, compounds with anticancer mechanisms similar to that of
      paclitaxel (Taxol), are produced by strains of the myxobacterium Sorangium
      cellulosum, and the gene cluster responsible for epothilone biosynthesis is
      organised as a large operon. In this work, we showed that the 440-bp promoter
      regions of the operons from eight S. cellulosum strains have 94.27 % DNA sequence
      identity and 50 % variability in promoter activity in Escherichia coli. A primer
      extension analysis revealed two transcriptional start sites (TSSs) at 246 (TSS1)
      and 193 bp (TSS2) upstream of the translation start site (TLS), respectively.
      Promoter truncation determined that the basal promoter from the So0157-2 strain
      is located within a 264-bp region containing weak promoter activity; whereas in
      the 38-bp region upstream, the 264-bp promoter was required for the strong
      promoter activity, which was dramatically increased by 11-fold in average. There
      was a conserved stem-loop structure between TSS2 and the TLS, which was
      identified in E. coli as a negative regulatory element. In addition, the upstream
      non-conserved 357-bp non-coding region contributes to the promoter activity,
      increasing it by 1.5-fold. In conclusion, the expression of the epothilone operon
      non-coding region in E. coli is regulated by a double promoter (with -35 and -10
      regions and two distinct TSSs), a stem-loop structure, and a distal non-coding
      region.

PMID- 23549747
TI  - Regioselective synthesis of flavonoid bisglycosides using Escherichia coli
      harboring two glycosyltransferases.
AB  - Regioselective glycosylation of flavonoids cannot be easily achieved due to the
      presence of several hydroxyl groups in flavonoids. This hurdle could be overcome
      by employing uridine diphosphate-dependent glycosyltransferases (UGTs), which use
      nucleotide sugars as sugar donors and diverse compounds including flavonoids as
      sugar acceptors. Quercetin rhamnosides contain antiviral activity. Two quercetin
      diglycosides, quercetin 3-O-glucoside-7-O-rhamnoside and quercetin 3,7-O
      bisrhamnoside, were synthesized using Escherichia coli expressing two UGTs. For
      the synthesis of quercetin 3-O-glucoside-7-O-rhamnoside, AtUGT78D2, which
      transfers glucose from UDP-glucose to the 3-hydroxyl group of quercetin, and
      AtUGT89C1, which transfers rhamnose from UDP-rhamnose to the 7-hydroxyl group of
      quercetin 3-O-glucoside, were transformed into E. coli. Using this approach, 67
      mg/L of quercetin 3-O-glucoside-7-O-rhamnoside was synthesized. For the synthesis
      of quercetin 3,7-O-bisrhamnoside, AtUGT78D1, which transfers rhamnose to the 3
      hydroxy group of quercetin, and AtUGT89C1 were used. The RHM2 gene from
      Arabidopsis thaliana was coexpressed to supply the sugar donor, UDP-rhamnose. E.
      coli expressing AtUGT78D1, AtUGT89C1, and RHM2 was used to obtain 67.4 mg/L of
      quercetin 3,7-O-bisrhamnoside.

PMID- 23549748
TI  - Nurses amidst change: the concept of change fatigue offers an alternative
      perspective on organizational change.
AB  - This article aims to clarify the concept of change fatigue and deems further
      exploration of the concept within the discipline of nursing is relevant and
      necessary. The concept of change fatigue has evolved from the discipline of
      management as a means to explore organization change and its associated triumphs
      and failures. Change fatigue has typically been described as one and the same as
      change resistance, with very little literature acknowledging that they are in
      fact distinct concepts. Concept clarification has highlighted the striking
      differences and few similarities that exist between the concepts of change
      fatigue and change resistance. Further exploration and subsequent research on the
      concept of change fatigue is needed within the discipline of nursing. The concept
      not only presents new and alternative perspectives on the processes of
      organization change, but provides opportunity for theory development that
      recognizes the impact organizational change has on nurses' work lives. 

PMID- 23549749
TI  - Legislation affecting governmental assistance for children of parents with
      substance use: a policy analysis of social justice.
AB  - There is legislation that withdraws governmental assistance where parents are
      using drugs. Social justice is an important consideration in any policy that
      modifies governmental assistance that benefits vulnerable children. The purpose
      of this policy analysis is to analyze identified legislation that effect
      governmental assistance for children in response to parents' substance misuse. A
      selective review of data-driven studies examined findings describing actual or
      potential effects on children of legislation targeting parental substance misuse.
      Challenges in design, processes, and implementation contribute to poor child
      outcomes. Identifiable constructs of social justice were missing in the reviewed
      legislation. Social injustice is a potential outcome for children when
      legislative intent focuses solely on addressing parental drug behaviors.
      Legislative alternatives to withdrawing support can address substance abuse while
      maintaining health promotion for these vulnerable children.

PMID- 23549750
TI  - Structures of polynuclear complexes of palladium(II) and platinum(II) formed by
      slow hydrolysis in acidic aqueous solution.
AB  - The aqua ions of palladium(II) and platinum(II) undergo extremely slow hydrolysis
      in strongly acidic aqueous solution, resulting in polynuclear complexes. The size
      and structures of these species have been determined by EXAFS and small angle X
      ray scattering, SAXS. For palladium(II), the EXAFS data show that the Pd-O and
      Pd...Pd distances are identical to those of crystalline palladium(II) oxide, but
      the intensities of the Pd...Pd distances in the Fourier transform at 3.04 and
      3.42 A are significantly lower compared to those of crystalline PdO. Furthermore,
      no Pd...Pd distances beyond 4 A are observed. These observations strongly
      indicate that the polynuclear palladium(II) complexes are oxido- and hydroxido
      bridged species with the same core structure as solid palladium(II) oxide. Based
      on the number of Pd...Pd distances, as derived from the EXAFS data, their size
      can be estimated to be approximately two unit cells, or ca. 1.0 nm(3). For
      platinum(II), EXAFS data of the polynuclear species formed in the slow hydrolysis
      process show Pt-O and Pt...Pt distances identical to those of amorphous
      platinum(II) oxide, precipitating from the solution studied. The Pt...Pt
      distances are somewhat different from those reported for crystalline platinum(II)
      oxide. The polynuclear platinum(II) complexes have a similar structure to the
      palladium ones, but they are somewhat larger, with an estimated diameter of 1.5
      3.0 nm. It has not been possible to precipitate any of these species by
      ultracentrifugation. They are detectable by SAXS, indicating diameters between
      0.7 and 2 nm, in excellent agreement with the EXAFS observations. The number of
      oxido- relative to hydroxido bridges will increase with increasing size of the
      complex. The charge of the complexes will remain about the same, +4, at growth,
      with approximate formulas [Pd10O4(OH)8(H2O)12](4+) and [Pt14O8(OH)8(H2O)12](4+)
      for complexes with a size of 2 and 3 unit cells of the corresponding solid metal
      oxide, respectively. Their high ionic charge in acidic aqueous solution will
      result in a stabilizing hydration shell.

PMID- 23549751
TI  - Brain delivery of NAP with PEG-PLGA nanoparticles modified with phage display
      peptides.
AB  - PURPOSE: A phage-displayed peptide TGN was used as a targeting motif to help the
      delivery of NAP-loaded nanoparticles across the blood-brain barrier (BBB), which
      sets an obstacle for brain delivery of NAP in vivo. METHODS:
      Intracerebroventricular injection of Abeta1-40 into mice was used to construct in
      vivo model of Alzheimer's disease. The water maze task was performed to evaluate
      the effects of the NAP formulations on learning and memory deficits in mice. The
      neuroprotective effect was tested by detecting acetylcholinesterase (AChE) and
      choline acetyltransferase (ChAT) activity and conducting histological assays.
      RESULTS: Intravenous administration of NAP-loaded TGN modified nanoparticles (TGN
      NP/NAP) has shown better improvement in spatial learning than NAP solution and
      NAP-loaded nanoparticles in Morris water maze experiment. The crossing number of
      the mice with memory deficits recovered after treatment with TGN-NP/NAP in a dose
      dependent manner. Similar results were also observed in AChE and ChAT activity.
      No morphological damage and no detectable Abeta plaques were found in mice
      hippocampus and cortex treated with TGN-NP/NAP. CONCLUSIONS: TGN modified
      nanoparticles could be a promising drug delivery system for peptide and protein
      drug such as NAP to enter the brain and play the therapeutic role.

PMID- 23549752
TI  - Caveolar uptake and endothelial-protective effects of nanostructured lipid
      carriers in acid aspiration murine acute lung injury.
AB  - PURPOSE: Nanostructured lipid carriers (NLC), nanosized
      phospholipids/triglyceride particles developed for drug delivery, are considered
      biologically inactive. We assessed the efficacy of unloaded NLC as experimental
      treatment for acute lung injury (ALI). METHODS: To induce ALI, C57Black/6 male
      mice received intratracheal injections of HCl or saline; A single dose of 16
      mg/Kg NLC or saline was injected intravenously concomitantly with HCl challenge.
      NLC uptake mechanisms and effects on endothelial permeability and signaling were
      studied in cultured endothelial cells and neutrophils. RESULTS: NLC pre-treatment
      attenuated pulmonary microvascular protein leak, airspace inflammatory cells,
      thrombin proteolytic activity and histologic lung injury score 24 h post insult.
      Using fluorescence measurements and flow cytometry in mouse lung microvascular
      endothelial cell culture homogenates, we determined that NLC rendered fluorescent
      by curcumin labeling are taken up by endothelial cells from mice expressing
      caveolin-1, the coat protein of caveolar endocytic vesicles, but not from
      caveolin-1 gene-disrupted mice, which lack caveolae. In contrast, conventional
      emulsions (CE), consisting of larger particles, were not incorporated. In
      addition, NLC pre-treatment of cultured human lung microvascular endothelial
      cells abrogated thrombin-induced activation of p44/42, albumin permeability
      response, actin cytoskeletal remodeling and interleukin-6 production. Finally,
      NLC but not CE abrogated lipopolysaccharide-triggered interleukin-8 release.
      CONCLUSIONS: NLC are engulfed by endothelial caveolae and possess endothelial
      protective effects. These novel properties may be of potential utility in ALI.

PMID- 23549753
TI  - Docetaxel-loaded thermosensitive and bioadhesive nanomicelles as a rectal drug
      delivery system for enhanced chemotherapeutic effect.
AB  - PURPOSE: To investigate the potential of thermosensitive and biadhesive
      nanomicelles in improving the bioavailability of docetaxel (DCT) and its
      chemotherapeutic effect. METHOD: DCT-loaded nanomicelles were prepared by
      emulsufication and characterized in terms of physico-chemical and visco-elastic
      parameters. The optimzed formulation was evaluated for in vivo localization,
      pharmacokinetic and anti-tumor efficacy. RESULTS: The hydrodynamic size of DCT
      loaded nanomicelles was approximately 13 nm and the nanomicelles exhibited a
      sufficient gelation strength (9250 mPa.s) and bioadhesive force (2100 dyn/cm2) to
      be retained in the upper part of rectum. We observed a high rectal
      bioavailability of 29% DCT compared to that following oral administration in
      rats, as it successfully evaded the multidrug efflux transporters and hepatic
      first-pass metabolism. Plasma concentration around ~50 ng/mL was maintained
      throughout the study period (12 h) while Taxotere(r) attained subtherapeutic
      range within 4 h of drug administration. Results also revealed that the rectally
      administered DCT-loaded nanomicelles exhibited a significant anti-tumor effect
      (200 mm3) with a reduced toxicity profile when compared to orally administered
      DCT (950 mm3). Furthermore, histological study showed that the rectal mucosa was
      completely intact with no signs of irritation upon treatment with DCT-loaded
      nanomicelles. CONCLUSIONS: Taken together, our novel thermosensitive and
      biadhesive nanomicelles demonstrated the ability to improve the bioavailability
      and chemotherapeutic potential of DCT in vivo. To the best of our knowledge, this
      is the first report describing the rectal delivery of DCT-loaded nanomicelles.

PMID- 23549754
TI  - Recommendations for the management of beta-lactam intolerance.
AB  - Beta-lactam intolerance, most of which is not IgE or even immunologically
      mediated even though it is commonly called an "allergy," can be safely managed
      using the following seven steps: 1. Avoid testing, re-challenging, or
      desensitizing individuals with histories of beta-lactam associated toxic
      epidermal necrolysis, Stevens-Johnson syndrome, drug reaction with eosinophilia
      and systemic symptoms syndrome, severe hepatitis, interstitial nephritis, or
      hemolytic anemia. 2. Avoid unnecessary antibiotic use, especially in the setting
      of viral infections. 3. Expect new intolerances to be reported after 0.5 to 4% of
      all antibiotic utilizations, dependent on gender and the specific antibiotic
      used. 4. Expect a higher incidence of new intolerances in individuals with three
      or more medication intolerances already noted in their medical records. 5. For
      individuals with an appropriate penicillin class antibiotic intolerance based on
      a history of anaphylaxis, urticaria, macular papular rashes, unknown symptoms, or
      symptoms not excluded in step one, proceed with penicillin skin testing. Skin
      test with penicilloyl-poly-lysine and native penicillin. If skin test is
      negative, proceed with an oral amoxicillin challenge. If skin test and oral
      challenge are negative, penicillin class antibiotics may be used. If skin test or
      oral challenge is positive, avoid penicillin class antibiotics. If skin test or
      oral challenge is positive, non-penicillin-beta-lactams may be used, unless there
      is a history of intolerance to a specific non-penicillin-beta-lactam, then avoid
      that specific non-penicillin-beta-lactam. If there is life-threatening infection
      that can only be treated with a penicillin class antibiotic, proceed with oral
      penicillin desensitization prior to any oral or parenteral penicillin use. 6. For
      individuals with an appropriate non-penicillin-beta-lactam intolerance, avoid re
      exposure to the beta-lactam implicated. An alternative beta-lactam may be used,
      ideally with different side chains. Penicillin allergy testing is not useful in
      the management of non-penicillin-beta-lactam intolerance. Non-penicillin-beta
      lactam skin testing is not clinically useful and should not be done outside of a
      research setting. If the non-penicillin-beta-lactam implicated is needed to treat
      a life-threatening infection, proceed with desensitization. 7. Be ready to treat
      anaphylaxis with all parenteral beta-lactam use.

PMID- 23549755
TI  - Effects of stimuli shape and polarization in evoking deimatic patterns in the
      European cuttlefish, Sepia officinalis, under varying turbidity conditions.
AB  - Cuttlefish possess the complex ability to identify approaching threats and then
      to selectively express the appropriate defense. We examined the visual cues used
      by Sepia officinalis cuttlefish during predator detection and the responses they
      selected. Using computer-generated stimuli, we set out to quantitate the deimatic
      responses to artificial looming stimuli of different shapes and contrasts.
      Defensive behavior gradually intensified as geometrical shapes resembled an image
      of a fish. Therefore, in addition to an object's size or its sudden increase in
      size, cuttlefish use form recognition to identify a threat. Cuttlefish
      demonstrated equal performance in predator detection trough clear water when
      presented with intensity versus polarization contrasts. However, when the water
      turbidity increased, the cuttlefish still detected looming fish shapes based on
      polarization contrast even when intensity information alone did not suffice.
      These results demonstrate the interplay between intensity and polarization
      information transmission and processing in the spatial domain. As nectobenthic
      organisms, cuttlefish probably experience low visibility conditions on a regular
      basis. The ability to see further into turbid water and to better detect an
      approaching object would be beneficial for their survival.

PMID- 23549757
TI  - Radiofrequency ablation for atrial fibrillation during concomitant cardiac
      surgery. Mid-term results.
AB  - BACKGROUND: Atrial fibrillation is found in an increasing number of patients
      undergoing open heart surgery. It is associated with higher mortality rates, risk
      of stroke and left ventricular dysfunction. Surgical ablation for atrial
      fibrillation has evolved from the complex"cut and sew" Maze procedure to less
      invasive techniques, utilizing alternative energy sources. We present our
      experience with left atrial radiofrequency ablation during cardiac surgery,
      outlining the technical aspects of the procedure and postoperative outcomes, with
      emphasis on mid-term freedom from atrial fibrillation. METHODS: The study
      included 93 consecutive patients with history of atrial fibrillation scheduled
      for cardiac surgery between January 2008 and December 2011. Concomitant left
      atrial radiofrequency ablation was performed using monopolar (endocardial) or
      bipolar (epicardial) systems, depending on the type of underlying cardiac
      pathology. Duration of the atrial fibrillation, re-do surgery, low ejection
      fraction, advanced age, or giant left atria were not considered as
      contraindications. RESULTS: Of the included patients, 73.1 % were discharged in
      stable sinus rhythm. Overall freedom from atrial fibrillation was 69.6 % at late
      follow-up, which ranged from 12 to 48 months (median, 22 months) and did not
      differ for the two approaches (epicardial vs. endocardial). The presence of early
      atrial tachyarrhythmia was a predictor of atrial fibrillation recurrence (p =
      0.026). Age was also associated with higher recurrence rates during hospital stay
      (p = 0.04), but not for late atrial fibrillation. CONCLUSION: Concomitant left
      atrial radiofrequency ablation conveyed satisfactory early and mid-term rhythm
      control, with acceptable postoperative outcomes, given the risk profile of our
      patient cohort.

PMID- 23549756
TI  - Synaptic plasticity in cephalopods; more than just learning and memory?
AB  - The outstanding behavioural capacity of cephalopods is underpinned by a highly
      sophisticated nervous system anatomy and neural mechanisms that often differ
      significantly from similarly complex systems in vertebrates and insects.
      Cephalopods exhibit considerable behavioural flexibility and adaptability, and it
      might be expected that this should be supported by evident cellular and synaptic
      plasticity. Here, we review what little is known of the cellular mechanisms that
      underlie plasticity in cephalopods, particularly from the point of view of
      synaptic function. We conclude that cephalopods utilise short-, medium-, and long
      term plasticity mechanisms that are superficially similar to those so far
      described in vertebrate and insect synapses. These mechanisms, however, often
      differ significantly from those in other animals at the biophysical level and are
      deployed not just in the central nervous system, but also to a limited extent in
      the peripheral nervous system and neuromuscular junctions.

PMID- 23549758
TI  - Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and
      mass spectrometry.
AB  - Metabolomic imaging of prostate cancer (PCa) aims to improve in vivo imaging
      capability so that PCa tumors can be localized noninvasively to guide biopsy and
      evaluated for aggressiveness prior to prostatectomy, as well as to assess and
      monitor PCa growth in patients with asymptomatic PCa newly diagnosed by biopsy.
      Metabolomics studies global variations of metabolites with which malignancy
      conditions can be evaluated by profiling the entire measurable metabolome,
      instead of focusing only on certain metabolites or isolated metabolic pathways.
      At present, PCa metabolomics is mainly studied by magnetic resonance spectroscopy
      (MRS) and mass spectrometry (MS). With MRS imaging, the anatomic image, obtained
      from magnetic resonance imaging, is mapped with values of disease condition
      specific metabolomic profiles calculated from MRS of each location. For example,
      imaging of removed whole prostates has demonstrated the ability of metabolomic
      profiles to differentiate cancerous foci from histologically benign regions.
      Additionally, MS metabolomic imaging of prostate biopsies has uncovered
      metabolomic expression patterns that could discriminate between PCa and benign
      tissue. Metabolomic imaging offers the potential to identify cancer lesions to
      guide prostate biopsy and evaluate PCa aggressiveness noninvasively in vivo, or
      ex vivo to increase the power of pathology analysis. Potentially, this imaging
      ability could be applied not only to PCa, but also to different tissues and
      organs to evaluate other human malignancies and metabolic diseases.

PMID- 23549759
TI  - Pharmacokinetic studies of bergapten in dog plasma by using a LC-MS/MS method
      studies.
AB  - A sensitive LC-MS/MS method was developed for the determination of bergapten in
      dog plasma. The chromatographic separation was carried out on a Hypersil ODS
      column with a mobile phase consisting of methanol-water. The plasma sample was
      precipitated with methanol and prepare for injecting onto the LC-MS/MS system.
      The detection was performed on a triple quadrupole tandem mass spectrometer by
      MRM via electro spray ionization source. The standard curve for bergapten was
      linear over the concentration range of 0.5-500 ng/mL with a lower limit of
      quantification of 0.5 ng/mL. The inter-day and intra-day precision (R.S.D.%) for
      bergapten varied between 3.4 and 11.5. The corresponding inter-day and intra-day
      accuracy (Bias%) ranged between -3.8 and 6.9. For the pharmacokinetic analysis of
      serum, the mean (SD) values obtained for the bergapten were as follows: Cmax,
      228.5 (14.3) ng/ml; Tmax, 4.2 (0.4) h; t1/2, 6.9 (2.3) h; AUC0-t h, 2507.2
      (168.5) ng . h/mL and AUC0-infinity, 3 219.2 (211.4) ng . h/mL, respectively. 

PMID- 23549760
TI  - The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the
      global POEM experience.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) represents a Natural Orifice
      Transluminal Endoscopic Surgery (NOTES) approach to Heller myotomy. Even though
      we are now entering an exponential phase of growth with a large number of centers
      interested in POEM, published data to guide them are limited. As part of the July
      2012 NOSCAR meeting, a conference was organized to review POEM and develop a
      consensus document. Authors SNS and TS who chaired the NOSCAR panel recognized
      the dearth of published data, which also may lag the rapid developments in POEM.
      Therefore, they undertook a survey of early POEM adopters around the world to
      rapidly obtain global, extensive, and current data on POEM. The raw survey data
      were made available to NOSCAR panel participants to assist with their
      presentations. We summarize the salient findings of the survey. METHODS: A
      comprehensive POEM survey was created and tested. The final survey instrument
      consisted of 197 questions that covered all aspects of POEM, including operator
      discipline, prior training, patient selection, setting, technique preference,
      results, adverse events, regulatory requirements, and perspectives on the future.
      An automated online response collector was used. RESULTS: The International Per
      Oral Endoscopic Myotomy Survey (IPOEMS) involved 16 expert centers, 7 in North
      America, 5 in Asia, 4 in Europe, including all high-volume centers (>=30 POEMs
      per center), as of July 2012. These centers had performed 841 POEMs. There were
      modest variations among centers in technique and periprocedural management, but
      all centers uniformly reported excellent efficacy and safety outcomes.
      CONCLUSIONS: The international POEM survey provides a "global snapshot" of the
      experience of early adopters. The excellent outcomes over a large cumulative
      volume of procedures are in line with those of published small series and lend
      further support to the notion that POEM represents a paradigm shift in the
      treatment of achalasia.

PMID- 23549761
TI  - Initial experience from a large referral center with robotic-assisted Ivor Lewis
      esophagogastrectomy for oncologic purposes.
AB  - BACKGROUND: We report our initial experience of patients undergoing robotic
      assisted Ivor Lewis esophagogastrectomy (RAIL) for oncologic purposes at a large
      referral center. METHODS: A retrospective review of all consecutive patients
      undergoing RAIL from 2010-2011 was performed. Basic demographics were recorded.
      Oncologic variables recorded included: tumor type, location, postoperative tumor
      margins, and nodal harvest. Immediate 30-day postoperative complications also
      were analyzed. RESULTS: Fifty patients underwent RAIL with median age of 66
      (range 42-82) years. The mean body mass index was 28.6 +/- 0.7 kg/m(2); 54% and
      the majority had an American Society of Anesthesiologists classification of 3.
      The mean and median number of lymph nodes retrieved during surgery was 20 +/- 1.4
      and 18.5 respectively. R0 resections were achieved in all patients. Postoperative
      complications occurred in 14 (28%) patients, including atrial fibrillation in 5
      (10%), pneumonia in 5 (10%), anastomotic leak in 1 (2%), conduit staple line leak
      in 1 (2%), and chyle leak in 2 (4%). The median ICU stay and length of
      hospitalization (LOH) were 2 and 9 days respectively. Total mean operating time
      calculated from time of skin incision to wound closure was 445 +/- 85 minutes;
      however, operative times decreased over time. Similarly, there was a trend toward
      lower complications after the first 29 cases but this did not reach statistical
      significance. There were no in-hospital mortalities. CONCLUSIONS: We demonstrated
      that RAIL for esophageal cancer can be performed safely and may be associated
      with fewer complications after a learning curve, shorter ICU stay, and LOH.

PMID- 23549762
TI  - Clinical and oncologic safety of laparoscopic surgery for obstructive left
      colorectal cancer following transanal endoscopic tube decompression.
AB  - BACKGROUND: Little information has been available concerning the safety of
      laparoscopic resection of obstructive colorectal cancer after transanal
      endoscopic tube decompression (TETD). The aim of this study was to assess the
      short- and long-term outcomes of laparoscopic surgery following TETD for such
      advanced colorectal cancer. METHODS: A retrospective review was performed of 40
      patients with obstructive left colorectal cancer whose distended bowels were
      treated with TETD before laparoscopic surgery, between January 2001 and March
      2011 (TETD group). The elective surgery resulted in potentially curative
      resection of the tumor in all cases. Their clinical records were compared to
      those of 80 matched controls with nonobstructive left colorectal cancer resected
      laparoscopically during the same period (control group). RESULTS: Operative time,
      blood loss, and the rate of conversion to laparotomy were comparable between the
      two groups. There were no significant between-group differences in morbidity
      rates. Five-year overall survival rates in the TETD and control groups were 71.9
      and 75.4%, respectively, with no statistical difference. Disease-free survival
      rates after 5 years were also similar (TETD group, 64.5% vs. control group,
      66.3%). There were no significant differences between the two groups in
      recurrence rates and patterns. CONCLUSION: These results suggest that
      laparoscopic surgery following TETD is clinically and oncologically safe and
      could be a treatment of choice for obstructive left colorectal cancer.

PMID- 23549763
TI  - Thoracoscopic enucleation of esophageal leiomyoma in prone position and single
      lumen endotracheal intubation.
AB  - INTRODUCTION: Esophageal leiomyomas are the most common benign tumors of the
      esophagus. Surgical enucleation is warranted for symptomatic patients.
      Thoracoscopic enucleation is the preferable approach for being less invasive by
      avoiding the discomfort and complications associated to larger thoracic
      incisions. The purpose of this study was to review our experience with
      enucleation of esophageal leiomyoma using a prone-position thoracoscopy
      technique. METHODS: Between January 2009 and July 2012, ten patients underwent
      resection of esophageal leiomyoma by thoracoscopy approach in prone position.
      Indications for surgical treatment were symptomatic tumors (dysphagia). All
      patients were followed postoperatively for at least 3 months with contrast x-ray
      of the esophagus. After single-lumen endotracheal intubation (nonselective
      intubation) in supine, patients were placed in prone position. Pneumothorax was
      kept at 6 to 8 mmHg using CO2 insufflation. A myotomy was performed over the
      tumor using hook cautery carefully protecting the mucosa from injuries. The
      myotomy was closed with continuous sutures. RESULTS: The procedures were
      completed in the prone position in all cases, without any conversion. Mean
      operative time was 89.2 +/- 28.7 minutes. Bleeding was negligible, and there were
      no intraoperative or postoperative complications. No intensive care unit support
      was needed for any patient. Chest x-ray in the first postoperative day showed no
      significant changes in any patient. The mean hospital stay was 3.2 days. Contrast
      x-ray of the esophagus was normal in all patients at 3 months postoperatively.
      CONCLUSIONS: Thoracoscopic enucleation of esophageal leiomyoma is a feasible,
      simple, and safe procedure. Thoracoscopy in the prone position with CO2
      insufflation allows the use of usual technique of intubation and also provides
      optimal operative field. The advantages of the thoracoscopic approach are less
      postoperative discomfort and lower risk of complications from open thoracotomy
      (especially pulmonary).

PMID- 23549764
TI  - Intraocular pressure variation during colorectal laparoscopic surgery: standard
      pneumoperitoneum leads to reversible elevation in intraocular pressure.
AB  - BACKGROUND: The potential effects of laparoscopic surgery on intra- and
      postoperative intraocular pressure (IOP) are not completely understood. Although
      prior studies have reported that pneumoperitoneum may increase IOP, it is not
      clear whether this increase is related to the effects of pneumoperitoneum or to
      the patient's position, such as the Trendelenburg position. This study aimed to
      evaluate the potential fluctuations of IOP during colorectal laparoscopic surgery
      in two groups of patients: those with and those without Trendelenburg
      positioning. METHODS: For this prospective study 45- to 85-year-old patients
      undergoing laparoscopic colorectal surgery were enrolled after a thorough
      ophthalmologic assessment. The study protocol included measurement of IOP at
      eight different time points (before, during, and after surgery) using a contact
      tonometer in both eyes. RESULTS: The study enrolled 29 patients: 17 (58.6%) with
      Trendelenburg position placement during surgery and 12 (41.4%) without
      Trendelenburg positioning. The two groups did not differ in terms of gender, age,
      body mass index (BMI), American Society of Anesthesiology (ASA) class, or
      operative time. In all the patients, pneumoperitoneum induction led to a mild
      rise in IOP, averaging 4.1 mmHg. The patients with Trendelenburg positioning
      showed a greater increase than the patients without it (5.05 vs 4.23 mmHg at 45
      min; p = 0.179), but IOP evaluation 48 h after surgery showed no substantial
      differences between the two groups. Among the 29 patients, 17 (58.6%) showed an
      increase in IOP of 5 mmHg or more during surgery. A greater percentage of the
      patients who underwent Trendelenburg positioning showed an IOP increase of 5 mmHg
      or more (76.5 vs 33.3%; p = 0.020). At the multivariate analysis, no potential
      predictors of increased IOP during surgery was identified. CONCLUSIONS: Standard
      pneumoperitoneum (<=14 mmHg) led to mild and reversible IOP increases. A trend
      was observed toward a greater IOP increase in patients with Trendelenburg
      positioning. Thus, the patient's position during surgery may represent a stronger
      risk factor for IOP increase than pneumoperitoneum-related intraabdominal
      pressure.

PMID- 23549765
TI  - Systematic pancreatic stenting after endoscopic snare papillectomy may reduce the
      risk of postinterventional pancreatitis.
AB  - BACKGROUND: Pancreatitis is the most feared complication of endoscopic
      papillectomy (EP). Prevention by pancreatic duct stenting following EP has been
      advocated but not proven by a randomized trial. The purpose of the present
      retrospective review is to compare a period of systematic stenting with the
      period before in which stents were placed selectively. METHODS: A total of 107
      patients undergoing EP from February 1999 to December 2009 were retrospectively
      reviewed. After an initial period with selective stenting (dilated duct, previous
      pancreatitis) between 1999 and 2002 (n = 24, group 1), stents were placed
      routinely after EP unless pancreas divisum was diagnosed (2002-2009; n = 83,
      group 2) to reduce postpapillectomy acute pancreatitis (PAP). PAP rates defined
      by Consensus Criteria were compared in the two periods. RESULTS: Five patients in
      group 1 were selected to receive a pancreatic stent (21%); in group 2 stenting
      was successful in 75 of 78 patients (success rate 96%) without pancreas divisum
      (n = 5). Overall, PAP occurred in 11% of patients. PAP rate was significantly
      reduced after introduction of systematic pancreatic stenting (5 vs 25%; p = 0.01)
      and occurred less often in stented than in nonstented patients: (5% (4/80) vs 27%
      (6/22), p = 0.0019). PAP also occurred in one of five patients with pancreas
      divisum. Selective stenting of patients also was an independent risk factor for
      PAP (OR 13, p = 0.001) in a multivariate analysis. CONCLUSIONS: Attempts at
      systematic stenting after EP pancreatic stenting appears to prevent PAP. Results
      should be corroborated by a randomized trial.

PMID- 23549766
TI  - Predictive factors for the diagnosis of severe acute cholecystitis in an
      emergency setting.
AB  - BACKGROUND: The aim of this study was to assess predictive factors for the
      diagnosis of severe acute cholecystitis. METHODS: The medical records of 295
      patients with pathologically confirmed acute cholecystitis were reviewed.
      Patients were divided, based on pathology findings, into a group with nonsevere
      acute cholecystitis and a group with severe acute cholecystitis. Preoperative
      data were compared by univariate and multivariate analyses. Therefore, diagnostic
      values were assessed based on the statistically significant predictive factors.
      The same approach was attempted for differential diagnosis between gangrenous and
      phlegmonous cholecystitis. RESULTS: Among ten variables found to be significantly
      different at univariate analysis, four were found to be independent predictive
      factors of severe acute cholecystitis: fever, distension of the gallbladder, wall
      edema, and preoperative adverse events. Common bile duct stones were confirmed as
      a protective factor. Leukocyte count, cardiovascular diseases, age, gender, and
      diabetes were not found to be significant predictive factors of severe acute
      cholecystitis. No differences were found in any of the preoperative data by
      comparing phlegmonous and gangrenous cholecystitis. CONCLUSION: Severe acute
      cholecystitis may be differentiated preoperatively from nonsevere acute
      cholecystitis based on clinical and US data, and predictive diagnostic values may
      be estimated according to the number of observed predictive factors. No
      differences were found when comparing phlegmonous and gangrenous cholecystitis.

PMID- 23549767
TI  - A nationwide examination of outcomes of percutaneous cholecystostomy compared
      with cholecystectomy for acute cholecystitis, 1998-2010.
AB  - BACKGROUND: Improvements in percutaneous drainage techniques combined with the
      recognized advantages of avoiding surgery in critically ill patients have
      rendered cholecystostomy an attractive treatment option, particularly in those
      patients with acute acalculus cholecystitis. However, robust data to guide
      surgeons in choosing cholecystostomy versus cholecystectomy have been lacking.
      METHODS: Retrospective analysis of the Nationwide Inpatient Sample (NIS) database
      from 1998-2010 was performed. Patients identified as having acute cholecystitis
      (calculus and acalculus) were identified by ICD-9 diagnosis codes and further
      classified as having undergone cholecystostomy or cholecystectomy. Patients with
      both procedures were included in the cholecystectomy group. Patients with neither
      procedure and those younger than age 18 years were excluded. Multivariate
      analyses examined mortality, length of stay, total charges,
      gallbladder/gastrointestinal complications, or any complication. Results were
      adjusted for age, race, gender, Charlson comorbidity index, and teaching-hospital
      status. Subset analyses were performed among patients who survived and patients
      who died. RESULTS: A total of 248,229 calculus and 58,518 acalculus acute
      cholecystitis patients were analyzed. On unadjusted analysis, mortality, length
      of stay, and total charges were higher, but complication rates were lower, in
      patients with a cholecystostomy. Adjusted analysis showed lower odds of
      complications [calculus: odds ratio (OR) 0.3, p < 0.001; acalculus: OR 0.4, p <
      0.001] but higher odds of mortality, total charges, and LOS (calculus: mortality
      OR 5.2, p < 0.001, $29,113, p < 0.001, +5.1 days, p < 0.001; acalculus: mortality
      OR 3.7, p < 0.001; $43,771, p < 0.001, +6.2 days, p < 0.001) among patients who
      received cholecystostomy. Results were similar in subset analyses. CONCLUSIONS:
      Patients receiving cholecystostomy were more likely to be older and have more
      comorbidities. Among patients with calculus or acalculus cholecystitis, patients
      with cholecystostomy had decreased complication rates compared with patients with
      cholecystectomy. However, patients who received cholecystostomy had increased
      odds of death, longer length of stay, and higher total charges.

PMID- 23549768
TI  - Outcomes and predictive factors of "not self-completion" in gastric endoscopic
      submucosal dissection for novice operators.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has become the standard
      endoscopic treatment for gastric neoplasms because of its safety and high rate of
      curability; however, it is not easy for novice operators to learn the technique
      of ESD. In this study, predictive factors of gastric neoplasms in which novices
      could not finish ESD by self-completion were evaluated. METHODS: Eighty
      consecutive ESD procedures performed by four novice operators were
      retrospectively analyzed. Standard ESD procedures were performed using an
      insulation-tipped (IT) knife under supervision. Self-completion rates, procedure
      time, and complete resection rates were evaluated, and predictive factors for
      "not self-completion" were assessed. RESULTS: The overall self-completion rate
      and en bloc plus R0 resection rate were 87.5% (70/80) and 95.7 % (67/70),
      respectively. In "not self-completion" cases (n = 10), the procedure time was
      longer and resected specimens were larger than those in self-completion cases
      (83.7 +/- 47.3 min vs. 189.5 +/- 106.8 min, p < 0.05; 641.2 +/- 487.8 vs. 1,116
      +/- 480.4 mm(2), p < 0.01). Predictive factors of "not self-completion" were
      tumor location in the middle or upper third of the stomach or in the greater
      curvature and size of resected specimens larger than 900 mm(2). The self
      completion rate of ESD was decreased in cases with more than two predictive
      factors. CONCLUSIONS: For novice operators, tumor location and resected areas are
      predictive factors for failure to finish gastric ESD by self-completion.
      Selection of cancer lesions could be a key factor for effectiveness of ESD
      training.

PMID- 23549769
TI  - Assessment of basic laparoscopic skills on virtual reality simulator or box
      trainer.
AB  - INTRODUCTION: We investigated whether the peg transfer task is interchangeable
      between a VR simulator and a box trainer. Our research questions: (1) Are scores
      of the box trainer interchangeable with the virtual equivalent of the exercise;
      (2) does training on the box affect performance on the VR simulator and vice
      versa; and (3) which system is preferred? METHODS: Experienced laparoscopists and
      medical interns were randomly assigned to one of two groups (V or B). They
      performed eight repetitions of the peg transfer task (4 on each simulator system)
      following a crossover study design. Group B started on the box trainer and group
      V started on the VR simulator. Opinion of participants was evaluated by a
      questionnaire. RESULTS: A significant correlation was found between time to
      complete the task on the box and the VR simulator. The comparison of the
      performances per system showed that group B (N = 14) performed the peg transfer
      task on the VR simulator in significantly less time than group V (N = 14; p =
      0.014). Overall, the box was preferred over the VR simulator. CONCLUSIONS:
      Although performances on the box trainer and VR simulator were correlated, they
      were not interchangeable. The results also imply that assessment on the VR
      simulator after pretraining on the box is acceptable, whereas VR simulator
      training alone might not suffice to pass an assessment on a box trainer. More
      research is needed to validate the use of the VR simulator as a FLS and PLUS
      assessment instrument.

PMID- 23549770
TI  - Laparoendoscopic single-site (LESS) varicocelectomy with reusable components:
      comparison with the conventional laparoscopic technique.
AB  - BACKGROUND: This study aimed to compare laparoendoscopic single-site
      varicocelectomy (LESSV) with multiport laparoscopic varicocelectomy (MLV) in
      terms of intraoperative parameters and postoperative outcomes. METHODS: A
      retrospective case-control study investigated 10 male adolescents and 89 adults
      who underwent either LESSV or MLV at the authors' center. The reusable X-Cone
      single port was inserted transumbilically. A 5-mm 30 degrees  telescope was used
      together with a straight and a prebent laparoscopic instrument. The MLV procedure
      was performed using two 5-mm ports and one 10-mm port. RESULTS: Between January
      2009 and November 2012, 20 patients underwent LESSV and 79 patients underwent
      MLV. The demographic data were comparable between the two groups. The mean
      operating time was 59.1 +/- 15.5 min for LESSV and 51.2 +/- 14.4 min for MLV (P =
      0.04). In the LESSV group, no conversion to MLV was necessary. The hospital stay
      was 1.6 +/- 0.7 days in the LESSV group versus 1.8 +/- 0.5 days in the MLV group
      (P = 0.17). The postoperative pain scores did differ between the two groups. By
      day 2, significantly more patients in the LESSV group than in the MLV group fully
      recovered their normal physical activity (P = 0.02). Comparison of pre- and
      postoperative values showed relief of testicular pain and improvement of semen
      parameters for the majority of the patients. The overall incidence of
      complications was distributed equally between the two groups as follows:
      paresthesia of the upper thigh (8 %), wound infection (5 %), epididymitis (3 %)
      and hydrocele (4 %). All the patients in the LESSV group were fully satisfied
      with their cosmetic results compared with only 76 % of the patients in the MLV
      group (P = 0.01). CONCLUSIONS: The LESSV procedure performed with the reusable X
      Cone is as safe and efficient as MLV. After LESSV, the parameters measuring
      postoperative patient satisfaction are significantly improved. Given its reusable
      components, including prebent laparoscopic instruments, the X-Cone platform is a
      cost-effective alternative to disposable or homemade single ports.

PMID- 23549771
TI  - Biologic meshes are not superior to synthetic meshes in ventral hernia repair: an
      experimental study with long-term follow-up evaluation.
AB  - BACKGROUND: In laparoscopic incisional hernia repair, direct contact between the
      prosthesis and the abdominal viscera is inevitable, which may lead to an
      inflammatory reaction resulting in abdominal adhesion formation. This study
      compared five different synthetic and biologic meshes in terms of adhesion
      formation, shrinkage, incorporation, and histologic characteristics after a
      period of 30 and 90 days. METHODS: In 85 rats, a mesh was positioned
      intraperitoneally in direct contact with the viscera. Five different meshes were
      implanted: Prolene (polypropylene), Parietex composite (collagen-coated
      polyester), Strattice (porcine dermis, non-cross-linked), Surgisis (porcine small
      intestine submucosa, non-cross-linked), and Permacol (porcine dermis, cross
      linked). The meshes were tested in terms of adhesion formation, shrinkage, and
      incorporation after a period of 30 and 90 days. Additionally, collagen formation
      after 90 days was determined. RESULTS: Significantly less adhesion formation was
      observed with Parietex composite (5 %; interquartile range [IQR], 2-5 %) and
      Strattice (5 %; IQR, 4-10 %) in the long term. In contrast, organs were attached
      to Permacol with four of seven meshes (57 %), and adhesion coverage of Surgisis
      mesh was present in 66 % (IQR, 0-100 %) of the cases. After 90 days, the best
      incorporation was seen with the Parietex composite mesh (79 %; IQR, 61-83 %).
      After 90 days, major alterations in adhesion formation were seen compared with 30
      days. Histologically, Strattice and Parietex composite showed a new mesothelial
      layer on the visceral side of the mesh. Microscopic degradation and new collagen
      formation were seen in the Surgisis group. CONCLUSIONS: Parietex composite mesh
      demonstrated the best long-term results compared with all the other meshes. The
      biologic non-cross-linked mesh, Strattice, showed little adhesion formation and
      moderate shrinkage but poor incorporation. Biologic meshes are promising, but
      varying results require a more detailed investigation and demonstrate that
      biologic meshes are not necessarily superior to synthetic meshes. The significant
      changes that take place between 30 and 90 days should lead to careful
      interpretation of short-term experimental results.

PMID- 23549772
TI  - Navigation system for minimally invasive esophagectomy: experimental study in a
      porcine model.
AB  - BACKGROUND: Navigation systems potentially facilitate minimally invasive
      esophagectomy and improve patient outcome by improving intraoperative
      orientation, position estimation of instruments, and identification of lymph
      nodes and resection margins. The authors' self-developed navigation system is
      highly accurate in static environments. This study aimed to test the overall
      accuracy of the navigation system in a realistic operating room scenario and to
      identify the different sources of error altering accuracy. METHODS: To simulate a
      realistic environment, a porcine model (n = 5) was used with endoscopic clips in
      the esophagus as navigation targets. Computed tomography imaging was followed by
      image segmentation and target definition with the medical imaging interaction
      toolkit software. Optical tracking was used for registration and localization of
      animals and navigation instruments. Intraoperatively, the instrument was
      displayed relative to segmented organs in real time. The target registration
      error (TRE) of the navigation system was defined as the distance between the
      target and the navigation instrument tip. The TRE was measured on skin targets
      with the animal in the 0 degrees  supine and 25 degrees  anti-Trendelenburg
      position and on the esophagus during laparoscopic transhiatal preparation.
      RESULTS: On skin targets, the TRE was significantly higher in the 25 degrees 
      position, at 14.6 +/- 2.7 mm, compared with the 0 degrees  position, at 3.2 +/-
      1.3 mm. The TRE on the esophagus was 11.2 +/- 2.4 mm. The main source of error
      was soft tissue deformation caused by intraoperative positioning,
      pneumoperitoneum, surgical manipulation, and tissue dissection. CONCLUSION: The
      navigation system obtained acceptable accuracy with a minimally invasive
      transhiatal approach to the esophagus in a realistic experimental model. Thus the
      system has the potential to improve intraoperative orientation, identification of
      lymph nodes and adequate resection margins, and visualization of risk structures.
      Compensation methods for soft tissue deformation may lead to an even more
      accurate navigation system in the future.

PMID- 23549773
TI  - A series of Zn-4f heterometallic coordination polymers and a zinc complex
      containing a flexible mixed donor dicarboxylate ligand.
AB  - A new zinc compound, together with a corresponding series of Zn-4f heterometallic
      coordination polymers, namely, [Zn(H2PBDA)(PBDA)]n (1), {[Ln2(PBDA)2.2H2O]
      [Zn2(PBDA)2Cl2]}n [H2PBDA = 3-(pyridin-3-yl-oxy) benzene-1,2-dicarboxylic acid,
      and Ln = Pr(2), Nd(3), Eu(4), Gd(5), Dy(6), Ho(7), Er(8)] have been
      hydrothermally synthesized and characterized systematically. Polymers 2-8 feature
      two-dimensional (2D) 4,4 networks, containing the original 1D heterometallic
      double stranded chains composed of [Ln2Zn2(PBDA)2] entities. The extensive
      hydrogen bonding and pi-pi stacking interactions were observed to stabilize the
      extended architectures. The luminescence emission spectra of the polymers vary
      depending on the lanthanide(III) ion present. Informative magnetic susceptibility
      measurements show that the same carboxylate bridging fashion of the PBDA ligand
      results in the different magnetic properties occurring within the heterometallic
      coordination polymers. In addition, polymer 6 exhibits an interesting slow
      magnetic relaxation behavior at lower temperatures.

PMID- 23549774
TI  - Drug-related problems found in children attending an emergency department in
      Saudi Arabia and in the United Kingdom.
AB  - BACKGROUND: No published studies investigating drug-related problems (DRPs) in
      children visiting emergency department (ED) in either the Kingdom of Saudi Arabia
      (KSA) or the United Kingdom (UK) were identified. OBJECTIVE: To determine the
      frequency and characteristics of DRPs in paediatric patients attending ED in the
      KSA and the UK. METHOD: An observational study. DRPs were identified by a
      researcher, reviewing the medical records of children attending the ED during a
      three-month period in KSA and a 1 month period in UK; severity and preventability
      of the DRPs were assessed. Incidence of DRPs overall and in each country was
      calculated. RESULTS: A total of 253 patients (KSA n = 143, UK n = 110) were
      included. Fifty-five patients (22%; 55/253), experienced 69 DRPs. 2% (5/253) of
      the patients attended the ED due to DRPs. Overall incidence was 21.7% (95% CI,
      16.8-27.3). 78% (54/69) of the DRPs were assessed as preventable; 33% (23/69) as
      of moderate severity. CONCLUSION: DRPs were common in paediatric patients
      attending EDs; the majority were preventable. Further study is needed to
      investigate the impact of mild and moderate DRPs on paediatric patients' health
      and also to improve the care provided to minimise the occurrence of preventable
      DRPs.

PMID- 23549775
TI  - The use of iloprost in the treatment of 'out of proportion' pulmonary
      hypertension in chronic obstructive pulmonary disease.
AB  - CASE: Pulmonary hypertension secondary to respiratory disease most often occurs
      as a complication of chronic obstructive pulmonary disease, which currently
      constitutes one of the leading causes of death. Some patients with hypoxaemia
      reveal "out of proportion" pulmonary hypertension with inappropriate increase of
      pulmonary artery pressure. Iloprost, analogue of prostacyclin, dilates systemic
      vessels and pulmonary vessels in particular if administered by inhalation. It
      appears to be important, life-saving, complementary therapy. However, there is no
      evidence for its routine use in out of proportion arterial pulmonary
      hypertension. This case study presents a 44-year old man with chronic obstructive
      pulmonary disease and "out of proportion" pulmonary hypertension. We present the
      results of his treatment with iloprost. CONCLUSION: In a patient with "out of
      proportion" pulmonary hypertension due to chronic obstructive pulmonary disease,
      inhaled iloprost led to improvement in clinical status and echocardiographic
      parameters, including a reduction of right ventricular systolic pressure.

PMID- 23549776
TI  - Expanded prescribing: a comparison of the views of Australian hospital and
      community pharmacists.
AB  - BACKGROUND: Community pharmacies and hospitals are the two main professional
      areas for pharmacists. There is currently a lack of comparison of pharmacists
      working in these two distinct settings in relation to an expanded prescribing
      role. OBJECTIVE: To compare the attitudes of hospital and community pharmacists
      regarding an expanded prescribing role. SETTING: Australian pharmacists. METHODS:
      A self-administered postal survey was used to collect the data. Data analysis was
      performed using SPSS((r)) v19. Kendall's tau-c test was used to compare the mean
      values between categorical variables (i.e. hospital or community pharmacists) and
      continuous variables measuring attitudes on a Likert scale (i.e. reasons in
      favour and barriers of pharmacist prescribing, preferred therapeutic areas of
      prescribing and prescribing models). A Chi square test was used to analyse
      categorical variables (i.e. demographics). MAIN OUTCOME MEASURE: The opinion of
      hospital and community pharmacists regarding an expanded prescribing role.
      RESULTS: A response rate of 40.4% was achieved (1,049/2,592). Where significant
      differences were located, community pharmacists were more supportive of all
      proffered potential reasons in favour of pharmacist prescribing (p < 0.05)
      whereas hospital pharmacists were more in agreement with all suggested barriers
      to such a role (p < 0.05). In a supplementary (collaborative) prescribing model,
      hospital pharmacists were more confident than community pharmacists in
      prescribing for heart failure (p < 0.001) and anticoagulant therapies (p =
      0.004). In an independent prescribing model hospital pharmacists were more
      supportive of prescribing anticoagulant therapies (p = 0.002). Significant
      differences were found between the two groups in relation to their support for
      independent prescribing (p = 0.020) and extension of the emergency supply 3 days
      rule to 30 days (p = 0.011). CONCLUSION: This study suggests that there are
      differences between hospital and community pharmacists in what they regard as
      potential reasons in favour of an expanded pharmacist prescribing role, perceived
      barriers to such a role and whether to prescribe independently of doctors.
      Hospital pharmacists' attitudinal differences in terms of support for certain
      therapeutic areas of prescribing reflects probably their existing active role in
      clinical decision making processes in patients who are often seriously ill.

PMID- 23549778
TI  - New evidence for an association between liver enzymes and pancreatic islet beta
      cell dysfunction in young obese patients.
AB  - To explore the relationship between serum liver enzymes and both the glucose
      tolerance status and insulin secretion in young obese patients. A total of 734
      young obese patients (BMI >= 25 kg m(-2)) and 231 lean healthy volunteers matched
      in age (BMI < 23 kg m(-2)) were enrolled in this cross-sectional observational
      study. The 734 obese patients were subdivided to three groups (OB-NGR, OB-IGR,
      and OB-DM) according to their glucose tolerance status. FSIVGTT was performed to
      assess the degree of insulin sensitivity (SI) and islet secretion function
      (AIRg). The disposition index (DI; product of SI and AIRg) was calculated as an
      integrated measurement of insulin secretion and insulin action after compensating
      for insulin resistance. The extent and distribution of hepatic fat infiltration
      was assessed using the liver/spleen ratio (L/S ratio) with CT scan. ALT and GGT
      levels in OB-NGR, OB-IGR, and OB-DM groups were significantly increased compared
      to the normal controls, and were incrementally increased in turn in the three
      groups, whereas DI decreased at the same time. One standard deviation increment
      in ALT and GGT increased the risk of beta-cell dysfunction after controlling for
      potential confounders such as sex, age, BMI, waist-hip ratio, and blood pressure.
      Even after the adjustment of the serum lipid profile and L/S ratio, the odds
      ratio of ALT remained statistically significant (OR, 1.603; 95 % CI, 1.225
      2.096). Serum levels of liver enzymes showed an independent close relationship
      with insulin secretion capacity. Excluding the impact of a fatty liver, increased
      ALT and GGT levels indicated a significant association with the attenuation of
      pancreatic beta-cell function. This study provides the possibility that elevated
      liver enzymes might be treated as simple biomarkers of early insulin secretion
      deficit in type 2 diabetes, especially in young obese patients.

PMID- 23549779
TI  - Do patients registered with CAM-trained GPs really use fewer health care
      resources and live longer? A reply to Christopher James Sampson.

PMID- 23549780
TI  - Quasi-VMAT in high-grade glioma radiation therapy.
AB  - PURPOSE: To compare a quasi-volumetric modulated arc therapy (qVMAT) with three
      dimensional conformal radiation therapy (3D-CRT) and intensity-modulated
      radiation therapy (IMRT) for the treatment of high-grade gliomas. The qVMAT
      technique is a fast method of radiation therapy in which multiple equispaced
      beams analogous to those in rotation therapy are radiated in succession. PATIENTS
      AND METHODS: This study included 12 patients with a planning target volume (PTV)
      that overlapped at least one organ at risk (OAR). 3D-CRT was planned using 2-3
      non-coplanar beams, whereby the field-in-field technique (FIF) was used to divide
      each field into 1-3 subfields to shield the OAR. The qVMAT strategy was planned
      with 15 equispaced beams and IMRT was planned using 9 beams with a total of 80
      segments. Inverse planning for qVMAT and IMRT was performed by direct machine
      parameter optimization (DMPO) to deliver a homogenous dose distribution of 60 Gy
      within the PTV and simultaneously limit the dose received by the OARs to the
      recommended values. Finally, the effect of introducing a maximum dose objective
      (max. dose < 54 Gy) for a virtual OAR in the form of a 0.5 cm ring around the PTV
      was investigated. RESULTS: The qVMAT method gave rise to significantly improved
      PTV95% and conformity index (CI) values in comparison to 3D-CRT (PTV95% = 90.7 %
      vs. 82.0 %; CI = 0.79 vs. 0.74, respectively). A further improvement was achieved
      by IMRT (PTV95% = 94.4 %, CI = 0.78). In qVMAT and IMRT, the addition of a 0.5 cm
      ring around the PTV produced a significant increase in CI (0.87 and 0.88,
      respectively), but dosage homogeneity within the PTV was considerably reduced
      (PTV95% = 88.5 % and 92.3 %, respectively). The time required for qVMAT dose
      delivery was similar to that required using 3D-CRT. CONCLUSION: These findings
      suggest that qVMAT should be preferred to 3D-CRT for the treatment of high-grade
      gliomas. The qVMAT method could be applied in hospitals, for example, which have
      limited departmental resources and are not equipped with systems capable of VMAT
      delivery.

PMID- 23549782
TI  - [Liver colorectal metastases <= 3 cm can be safely treated with percutaneous
      radiofrequency ablation. A 10-year follow-up].

PMID- 23549781
TI  - Effect of a combined surgery, re-irradiation and hyperthermia therapy on local
      control rate in radio-induced angiosarcoma of the chest wall.
AB  - PURPOSE: Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor
      prognosis due to the high percentage of local failures. The efficacy and side
      effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in
      combination with surgery were assessed in RAS patients. PATIENTS AND METHODS: RAS
      was diagnosed in 23 breast cancer patients and 1 patient with melanoma. These
      patients had previously undergone breast conserving therapy (BCT, n = 18),
      mastectomy with irradiation (n=5) or axillary lymph node dissection with
      irradiation (n = 1). Treatment consisted of surgery followed by reRT + HT (n =
      8), reRT + HT followed by surgery (n = 3) or reRT + HT alone (n = 13). Patients
      received a mean radiation dose of 35 Gy (32-54 Gy) and 3-6 hyperthermia
      treatments (mean 4). Hyperthermia was given once or twice a week following
      radiotherapy (RT). RESULTS: The median latency interval between previous
      radiation and diagnosis of RAS was 106 months (range 45-212 months). Following
      reRT + HT, the complete response (CR) rate was 56 %. In the subgroup of patients
      receiving surgery, the 3-month, 1- and 3-year actuarial local control (LC) rates
      were 91, 46 and 46 %, respectively. In the subgroup of patients without surgery,
      the rates were 54, 32 and 22 %, respectively. Late grade 4 RT toxicity was seen
      in 2 patients. CONCLUSION: The present study shows that reRT + HT treatment-
      either alone or combined with surgery--improves LC rates in patients with RAS.

PMID- 23549783
TI  - During post-natal human myogenesis, normal myotube size requires TRPC1- and TRPC4
      mediated Ca2+ entry.
AB  - Myogenesis involves expression of muscle-specific transcription factors such as
      myogenin and myocyte enhancer factor 2 (MEF2), and is essentially regulated by
      fluctuations of cytosolic Ca(2+) concentration. Recently we demonstrated that
      molecular players of store-operated Ca(2+) entry (SOCE), stromal interacting
      molecule (STIM) and Orai, were fundamental in the differentiation process of post
      natal human myoblasts. Besides STIM and Orai proteins, the family of transient
      receptor potential canonical (TRPC) channels was shown to be part of SOCE in
      several cellular systems. In the present study, we investigated the role of TRPC
      channels in the human myogenesis process. We demonstrate, using an siRNA strategy
      or dominant negative TRPC overexpression, that TRPC1 and TRPC4 participate in
      SOCE, are necessary for MEF2 expression, and allow the fusion process to generate
      myotubes of normal size. Conversely, the overexpression of STIM1 with TRPC4 or
      TRPC1 increased SOCE, accelerated myoblast fusion, and produced hypertrophic
      myotubes. Interestingly, in cells depleted of TRPC1 or TRPC4, the normalization
      of SOCE by increasing the extracellular calcium concentration or by
      overexpressing STIM1 or Orai1 was not sufficient to restore normal fusion
      process. A normal differentiation occurred only when TRPC channel was re
      expressed. These findings indicate that Ca(2+) entry mediated specifically by
      TRPC1 and TRPC4 allow the formation of normal-sized myotubes.

PMID- 23549784
TI  - The kinesin-like protein TOP promotes Aurora localisation and induces
      mitochondrial, chloroplast and nuclear division.
AB  - The cell cycle usually refers to the mitotic cycle, but the cell-division cycle
      in the plant kingdom consists of not only nuclear but also mitochondrial and
      chloroplast division cycle. However, an integrated control system that initiates
      division of the three organelles has not been found. We report that a novel C
      terminal kinesin-like protein, three-organelle division-inducing protein (TOP),
      controls nuclear, mitochondrial and chloroplast divisions in the red alga
      Cyanidioschyzon merolae. A proteomics study revealed that TOP is a member of a
      complex of mitochondrial-dividing (MD) and plastid-dividing (PD) machineries
      (MD/PD machinery complex) just prior to constriction. After TOP localizes at the
      MD/PD machinery complex, mitochondrial and chloroplast divisions occur and the
      components of the MD/PD machinery complexes are phosphorylated. Furthermore, we
      found that TOP downregulation impaired both mitochondrial and chloroplast
      divisions. MD/PD machinery complexes were formed normally at each division site
      but they were neither phosphorylated nor constricted in these cells.
      Immunofluorescence signals of Aurora kinase (AUR) were localized around the MD
      machinery before constriction, whereas AUR was dispersed in the cytosol by TOP
      downregulation, suggesting that AUR is required for the constriction. Taken
      together our results suggest that TOP induces phosphorylation of MD/PD machinery
      components to accomplish mitochondrial and chloroplast divisions prior to nuclear
      division, by relocalization of AUR. In addition, given the presence of TOP
      homologs throughout the eukaryotes, and the involvement of TOP in mitochondrial
      and chloroplast division may illuminate the original function of C-terminal
      kinesin-like proteins.

PMID- 23549785
TI  - ERK2 but not ERK1 mediates HGF-induced motility in non-small cell lung carcinoma
      cell lines.
AB  - Aberrant signalling of receptor tyrosine kinases (RTKs), such as c-Met, the
      receptor for hepatocyte growth factor (HGF), has been implicated in the
      oncogenesis of various tumours including non-small cell lung carcinoma (NSCLC).
      Through its pro-migratory properties, c-Met has been implicated specifically in
      the process of tumour metastasis, demanding a better understanding of the
      underlying signalling pathways. Various players downstream of c-Met have been
      well characterised, including the extracellular-signal-regulated kinases (ERKs) 1
      and 2. In a small interfering RNA (siRNA)-based high-throughput wound healing
      screen performed in A549 lung carcinoma cells, we identified ERK2 but not ERK1 as
      a strong mediator of HGF-induced motility. This finding was confirmed in several
      NSCLC cell lines as well as in HeLa cells. One known substrate for ERK kinases in
      cell migration, the focal adhesion protein paxillin, was also one of the hits
      identified in the screen. We demonstrate that HGF stimulation results in a time
      dependent phosphorylation of paxillin on serine 126, a process that can be
      blocked by inhibition of the ERK1/2 upstream kinase mitogen-activated protein
      kinase/ERK kinase 1 (MEK1) or inhibition of glycogen synthase kinase 3 (GSK3).
      Further, we show that paxillin turnover at focal adhesions is increased upon
      stimulation by HGF, an effect that is dependent on serine residues 126 (GSK3
      site) and 130 (ERK site) within paxillin. In line with the isoform-specific
      requirement of ERK2 for HGF-mediated migration in lung tumour cell models, ERK2
      but not ERK1 is shown to be responsible for paxillin serine 126 phosphorylation
      and its increased turnover at focal adhesions.

PMID- 23549786
TI  - Fine mapping of autophagy-related proteins during autophagosome formation in
      Saccharomyces cerevisiae.
AB  - Autophagy is a bulk degradation system mediated by biogenesis of autophagosomes
      under starvation conditions. In Saccharomyces cerevisiae, a membrane sac called
      the isolation membrane (IM) is generated from the pre-autophagosomal structure
      (PAS); ultimately, the IM expands to become a mature autophagosome. Eighteen
      autophagy-related (Atg) proteins are engaged in autophagosome formation at the
      PAS. However, the cup-shaped IM was visualized just as a dot by fluorescence
      microscopy, posing a challenge to further understanding the detailed functions of
      Atg proteins during IM expansion. In this study, we visualized expanding IMs as
      cup-shaped structures using fluorescence microscopy by enlarging a selective
      cargo of autophagosomes, and finely mapped the localizations of Atg proteins. The
      PAS scaffold proteins (Atg13 and Atg17) and phosphatidylinositol 3-kinase complex
      I were localized to a position at the junction between the IM and the vacuolar
      membrane, termed the vacuole-IM contact site (VICS). By contrast, Atg1, Atg8 and
      the Atg16-Atg12-Atg5 complex were present at both the VICS and the cup-shaped IM.
      We designate this localization the 'IM' pattern. The Atg2-Atg18 complex and Atg9
      localized to the edge of the IM, appearing as two or three dots, in close
      proximity to the endoplasmic reticulum exit sites. Thus, we designate these dots
      as the 'IM edge' pattern. These data suggest that Atg proteins play individual
      roles at spatially distinct locations during IM expansion. These findings will
      facilitate detailed investigations of the function of each Atg protein during
      autophagosome formation.

PMID- 23549787
TI  - Netrin-1-induced activation of Notch signaling mediates glioblastoma cell
      invasion.
AB  - Glioblastoma multiforme is an aggressively invasive human brain cancer, which
      lacks effective treatment. The axonal guidance protein, netrin-1, is
      overexpressed in glioblastoma tumor biopsies. In Matrigel invasion assays we
      observed that experimental overexpression of netrin-1 increased cell invasiveness
      and its downregulation decreased invasiveness. Using tandem affinity purification
      and mass spectrometry protein identification we found that netrin-1 forms a
      complex with both Notch2 and Jagged1. Recombinant netrin-1 colocalized with
      Jagged1 and Notch2 at the cell surface and was also present in the intracellular
      vesicles with Jagged1, but not with Notch2. Netrin-1 activated Notch signaling
      and subsequent glioblastoma cell invasion. Interestingly, the recombinant central
      domain of netrin-1 counteracted the effects of the full-length netrin-1: it
      inhibited glioblastoma cell invasion and Notch activation by retaining the Notch
      signaling complex at the cell surface. This finding may give rise to therapeutic
      applications. These results reveal a new mechanism leading to glioblastoma cell
      invasion, in which netrin-1 activates Notch signaling.

PMID- 23549788
TI  - The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.
AB  - Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are
      regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf)
      of small GTPases. They have been identified as modulators of various receptor
      tyrosine kinase signaling pathways including the insulin, the vascular epidermal
      growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These
      pathways control many cellular functions, including cell proliferation and
      differentiation, and their misregulation is often associated with cancerogenesis.
      In vivo studies on cytohesins using genetic loss of function alleles are lacking,
      however, since knockout mouse models are not available yet. We have recently
      identified mutants for the single cytohesin Steppke (Step) in Drosophila and we
      could demonstrate an essential role of Step in the insulin signaling cascade. In
      the present study, we provide in vivo evidence for a role of Step in EGFR
      signaling during wing and eye development. By analyzing step mutants, transgenic
      RNA interference (RNAi) and overexpression lines for tissue specific as well as
      clonal analysis, we found that Step acts downstream of the EGFR and is required
      for the activation of mitogen-activated protein kinase (MAPK) and the induction
      of EGFR target genes. We further demonstrate that step transcription is induced
      by EGFR signaling whereas it is negatively regulated by insulin signaling.
      Furthermore, genetic studies and biochemical analysis show that Step interacts
      with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a
      larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK
      activation.

PMID- 23549789
TI  - Microtubule motors mediate endosomal sorting by maintaining functional domain
      organization.
AB  - Many microtubule motors have been shown to couple to endosomal membranes. These
      motors include dynein in addition to many different kinesin family members.
      Sorting nexins (SNXs) are central to the organization and function of endosomes.
      These proteins can actively shape endosomal membranes and couple directly or
      indirectly to the minus-end microtubule motor dynein. Motor proteins acting on
      endosomes drive their motility, dictate their morphology and affect cargo
      segregation. We have used well-characterized members of the SNX family to
      elucidate motor coupling using high-resolution light microscopy coupled with
      depletion of specific microtubule motors. Endosomal domains labelled with SNX1,
      SNX4 and SNX8 couple to discrete combinations of dynein and kinesin motors. These
      specific combinations govern the structure and motility of each SNX-coated
      membrane in addition to the segregation of distinct functional endosomal
      subdomains. Taken together, our data show that these key features of endosome
      dynamics are governed by the same set of opposing microtubule motors. Thus,
      microtubule motors help to define the mosaic layout of endosomes that underpins
      cargo sorting.

PMID- 23549791
TI  - Depression in children and adolescents with epilepsy: a 15 year research review
      of prevalence, and demographic and seizure related correlates.
AB  - OBJECTIVE: The paper aims to study the prevalence of depression in epileptic
      children and adolescents by reviewing the existing literature, looking for any
      association between depression in these children and their demographic or seizure
      related factors to highlight the potential risk factors for depression in
      epileptic children. METHODS: A search of MEDLINE, NLM Gateway, Ovid and EMBASE
      was carried out to study original English language articles published during the
      last 15 years, focusing on only epileptic children and adolescents, studying of
      depression as comorbidity of epilepsy, and describing demographic and epilepsy
      related factors associated with depression. FINDINGS: The 11 articles included in
      this study have reported data on 1095 epileptic children aged 4-19 years old and
      showed that the prevalence of depression has continued to be very common in
      epileptic children and adolescents, ranged from 5.2% to 39.6%. On the whole, the
      findings did not support the presence of an association between depression and
      demographic or seizure variables in children. CONCLUSION: Pediatricians and other
      physicians working with epileptic children should have a high index of suspicion
      for depression as a comorbid condition in children with epilepsy. Early diagnosis
      and more comprehensive packages of care for depression in epileptic children will
      enable them to have a better quality of life.

PMID- 23549790
TI  - The genetic depletion or the triptolide inhibition of TFIIH in p53-deficient
      cells induces a JNK-dependent cell death in Drosophila.
AB  - Transcription factor IIH (TFIIH) participates in transcription, nucleotide
      excision repair and the control of the cell cycle. In the present study, we
      demonstrate that the Dmp52 subunit of TFIIH in Drosophila physically interacts
      with the fly p53 homologue, Dp53. The depletion of Dmp52 in the wing disc
      generates chromosome fragility, increases apoptosis and produces wings with a
      reduced number of cells; cellular proliferation, however, is not affected.
      Interestingly, instead of suppressing the apoptotic phenotype, the depletion of
      Dp53 in Dmp52-depleted wing disc cells increases apoptosis and the number of
      cells that suffer from chromosome fragility. The apoptosis induced by the
      depletion of Dmp52 alone is partially dependent on the JNK pathway. In contrast,
      the enhanced apoptosis caused by the simultaneous depletion of Dp53 and Dmp52 is
      absolutely JNK-dependent. In this study, we also show that the anti-proliferative
      drug triptolide, which inhibits the ATPase activity of the XPB subunit of TFIIH,
      phenocopies the JNK-dependent massive apoptotic phenotype of Dp53-depleted wing
      disc cells; this observation suggests that the mechanism by which triptolide
      induces apoptosis in p53-deficient cancer cells involves the activation of the
      JNK death pathway.

PMID- 23549792
TI  - Cost effectiveness of fecal DNA screening for colorectal cancer: a systematic
      review and quality appraisal of the literature.
AB  - BACKGROUND: Fecal DNA (fDNA) testing is a noninvasive potential alternative to
      current colorectal cancer screening tests. OBJECTIVE: We conducted a systematic
      review and quality assessment of studies of cost-effectiveness of fDNA as a
      colorectal cancer screening tool (compared with no screening and other screening
      modalities), and identified key variables that impinged on cost-effectiveness.
      DATA SOURCES: We searched MEDLINE, Embase, and the Centre for Reviews and
      Dissemination for cost-effectiveness studies of fDNA-based screening, published
      in English by September 2011. STUDY SELECTION: Studies that undertook an economic
      evaluation of fDNA, using either a cost-effectiveness or cost-utility analysis,
      compared with other relevant screening modalities and/or no screening were
      included. Additional inclusion criteria related to the presentation of data
      pertaining to model variables including time horizon, costs, fDNA performance
      characteristics, screening uptake, and comparators. A total of 369 articles were
      initially identified for review. After removing duplicates and applying inclusion
      and exclusion criteria, seven articles were included in the final review. STUDY
      APPRAISAL: Data was abstracted on key descriptor variables including screening
      scenarios, time horizon, costs, test performance characteristics, screening
      uptake, comparators, and incremental cost-effectiveness ratios. Quality
      assessment was undertaken using a standard checklist for economic evaluations.
      Studies cited by cost-effectiveness articles as the source of data on fDNA test
      performance characteristics were also reviewed. RESULTS: Seven cost-effectiveness
      studies were included, from the USA (4), Canada (1), Israel (1), and Taiwan (1).
      Markov models (5), a partially observable Markov decision process model (1) and
      MISCAN and SimCRC (1) microsimulation models were used. All studies took a third
      party payer perspective and one included, in addition, a societal perspective.
      Comparator screening tests, screening intervals, and specific fDNA tests varied
      between studies. fDNA sensitivity and specificity parameters were derived from 12
      research studies and one meta-analysis. Outcomes assessed were life-years gained
      and quality-adjusted life-years gained. fDNA was cost-effective when compared
      with no screening in six studies. Compared with other screening modalities, fDNA
      was not considered cost-effective in any of the base-case analyses: in five
      studies it was dominated by all alternatives considered. Sensitivity analyses
      identified cost, compliance, and test parameters as key influential parameters.
      In general, poor presentation of "study design" and "data collection" details
      lowered the quality of included articles. LIMITATIONS: Although the literature
      searches were designed for high sensitivity, the possibility cannot be excluded
      that some eligible studies may have been missed. Reports (such as Health
      Technology Assessments produced by government agencies) and other forms of grey
      literature were excluded because they are difficult to identify systematically
      and/or may not report methods and results in sufficient detail for assessment.
      CONCLUSION: On the basis of the available (albeit limited) evidence, while fDNA
      is cost-effective when compared with no screening, it is currently dominated by
      most of the other available screening options. Cost and test performance appear
      to be the main influences on cost-effectiveness.

PMID- 23549793
TI  - Time costs associated with informal care for colorectal cancer: an investigation
      of the impact of alternative valuation methods.
AB  - BACKGROUND: A societal perspective in economic evaluation necessitates that all
      resources associated with a disease or intervention should be valued; however,
      informal care time costs are rarely considered. OBJECTIVE: We estimated time
      allocated to care by informal carers of colorectal cancer survivors; and
      investigated the impact of applying alternative valuation methods to this time.
      METHODS: Colorectal cancer cases (ICD10 C18-C20) diagnosed 6-30 months previously
      and identified from the National Cancer Registry Ireland were invited to provide
      details of informal carers. Carers completed a postal questionnaire. Time
      estimates per week associated with hospital-related and domestic-related care
      activities were collected for two phases: diagnosis and initial treatment
      (initial 3 months) and ongoing care (previous 30 days). Seven valuation
      scenarios, based on variants of the opportunity cost approach (OCA), and the
      proxy good approach (PGA), were considered. The base-case was OCA with all carer
      time valued at the average national wage. RESULTS: We received 154 completed
      questionnaires (response rate = 68 %). Average weekly time allocated to caring
      was 42.5 h in the diagnosis and initial treatment phase and 16.9 h in the ongoing
      care phase. Under the base-case, average weekly time costs were <euro>295 (95 %
      CI 255-344) for hospital-related activities and <euro>630 (95 % CI 543-739) for
      domestic-related activities in the diagnosis and initial treatment phase and
      <euro>359 (95 % CI 293-434) in the ongoing care phase. PGA estimates were 23 %
      below the base-case. Only one alternative scenario (occupation and gender
      specific wages for carers in paid work and replacement wages for non-working
      carers) surpassed base-case costs, and the difference was modest. CONCLUSIONS:
      Overall, significant time is associated with informal caring in colorectal
      cancer. Different time valuation methods can produce quite different cost
      estimates. A standardised methodology for estimating informal care costs would
      facilitate better integration of these into economic evaluations.

PMID- 23549796
TI  - Tools to detect influenza virus.
AB  - In 2009, pandemic influenza A (H1N1) virus (H1N1 09) started to spread quickly in
      many countries. It causes respiratory infection with signs and symptoms of common
      infectious agents. Thus, clinicians sometimes may miss the H1N1 patient. Clinical
      laboratory tests are important for the diagnosis of the H1N1 infection. There are
      several tests available, however, the rapid test and direct fluorescence antigen
      test are unable to rule out the influenza virus infection and viral culture test
      is time consuming. Therefore, nucleic acid amplification techniques based on
      reverse transcription polymerase chain reaction assays are regarded as a specific
      diagnosis to confirm the influenza virus infection. Although the nucleic acid
      based techniques are highly sensitive and specific, the high mutation rate of the
      influenza RNA-dependent RNA polymerase could limit the utility of the techniques.
      In addition, their use depends on the availability, cost and throughput of the
      diagnostic techniques. To overcome these drawbacks, evaluation and development of
      the techniques should be continued. This review provides an overview of various
      techniques for specific diagnosis of influenza infection.

PMID- 23549797
TI  - Association between cerebrospinal fluid S100B protein and neuronal damage in
      patients with central nervous system infections.
AB  - PURPOSE: S100B protein is widely used as a measure of glial activity or damage in
      several brain conditions. Central nervous system (CNS) infections can cause
      neurological sequelae because of parenchyma invasion. It is difficult to predict
      further neuronal damage in the CNS infection. The present study is aimed to
      evaluate the role of the cerebrospinal fluid (CSF) S100B protein as an indicator
      of neuronal damage in CNS infection. MATERIALS AND METHODS: We measured the
      concentration of CSF S100B protein in 62 patients with a CNS infection using an
      Enzyme-Linked Immunosorbent Assay. The patients with CNS infections were
      classified as having no neuronal damage (CNS-N) or as having neuronal damage
      (CNS+N) according to the presence of neurological change or structural lesions on
      brain MRI. RESULTS: The CSF S100B protein level of the CNS+N group (n=22, 0.235
      MUg/L, 0.10-2.18) was significantly higher than that of the CNS-N group (n=40,
      0.087 MUg/L, 0.06-0.12) and control group (n=40, 0.109 MUg/L, 0.07-0.14, p<0.01).
      Using an arbitrary cut off value, S100B-positive CSF was detected in 2.5% of the
      CNS-N group and in 50% of the CNS+N group (p<0.05). CONCLUSION: These findings
      suggest that increased S100B protein levels in the CSF may be associated with the
      neuronal damage following CNS infections.

PMID- 23549795
TI  - Modulation of the transcriptional activity of peroxisome proliferator-activated
      receptor gamma by protein-protein interactions and post-translational
      modifications.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a nuclear
      receptor superfamily; members of which play key roles in the control of body
      metabolism principally by acting on adipose tissue. Ligands of PPARgamma, such as
      thiazolidinediones, are widely used in the treatment of metabolic syndromes and
      type 2 diabetes mellitus (T2DM). Although these drugs have potential benefits in
      the treatment of T2DM, they also cause unwanted side effects. Thus, understanding
      the molecular mechanisms governing the transcriptional activity of PPARgamma is
      of prime importance in the development of new selective drugs or drugs with fewer
      side effects. Recent advancements in molecular biology have made it possible to
      obtain a deeper understanding of the role of PPARgamma in body homeostasis. The
      transcriptional activity of PPARgamma is subject to regulation either by
      interacting proteins or by modification of the protein itself. New interacting
      partners of PPARgamma with new functions are being unveiled. In addition, post
      translational modification by various cellular signals contributes to fine-tuning
      of the transcriptional activities of PPARgamma. In this review, we will summarize
      recent advancements in our understanding of the post-translational modifications
      of, and proteins interacting with, PPARgamma, both of which affect its
      transcriptional activities in relation to adipogenesis.

PMID- 23549798
TI  - Quantitative analysis of simultaneous EEG features during PET studies for
      childhood partial epilepsy.
AB  - PURPOSE: To demonstrate the significance of simultaneous electroencephalography
      (EEG) recording during 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG)-positron emission
      tomography (PET) in childhood partial epilepsy. MATERIALS AND METHODS: We
      included 46 children with partial epilepsy who underwent simultaneous EEG during
      PET. We compared the epileptogenic area of several EEG features including
      epileptiform discharges, focal polymorphic slow waves, and electrographic
      seizures, with the abnormal metabolic region on PET. We also compared the
      epileptogenic area of simultaneous EEG and PET with findings on magnetic
      resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis
      of the resected cortical area, in eight patients who underwent surgical resection
      of the epileptogenic area. RESULTS: Hypometabolic regions on interictal PET were
      concordant with epileptogenic areas of epileptiform discharges and focal
      polymorphic slow waves, according to their frequency and/or severity, with odds
      ratios of 1.35 and 1.81, respectively (p<0.05). Hypermetabolic PET was also
      concordant with epileptogenic areas of ictal events longer than 20 seconds during
      the period of FDG uptake. Among the eight patients who underwent surgical
      resection, six patients, including two with non-lesional MRI, had concordant EEG
      and PET findings, were confirmed pathologically, and became seizure-free after
      surgery. CONCLUSION: Simultaneous EEG is useful in identifying epileptogenic
      areas due to a high concordance with abnormal PET metabolic areas. Moreover,
      simultaneous EEG may also prevent false lateralization of PET from postictal and
      mixed metabolism during ictal events, as well as abnormal hypermetabolism, during
      frequent interictal epileptiform discharges.

PMID- 23549799
TI  - Clinical characteristics and molecular genetic analysis of Korean patients with
      GNE myopathy.
AB  - PURPOSE: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE)
      myopathy is an autosomal recessive neuromuscular disorder characterized by early
      adult-onset weakness of the distal muscles of the lower limbs. The clinical
      spectrum of GNE myopathy varies, and it is not clear how the same GNE gene
      mutations can result in different phenotypes. Here, we present clinical,
      pathological and genetic characteristics of twenty-one Korean patients with GNE
      myopathy. MATERIALS AND METHODS: Twenty-one GNE myopathy patients were included
      in this study, conducted from 2004 to 2011. Based on medical records, patients'
      gender, onset age, family history, clinical history, serum creatine kinase (CK)
      level, neurologic examination, findings of muscle biopsy, muscle imaging findings
      and electrophysiologic features were extensively reviewed. Mutation of the GNE
      gene (9p13.3) was confirmed by DNA direct sequencing analysis in all patients.
      RESULTS: The mean onset age was 23.8+/-8.8 years (mean+/-SD). Patient serum CK
      levels were slightly to moderately elevated, ranging from 41 to 2610 IU. Among
      the patients, twelve patients were female and nine patients were male. Except for
      eight patients, all of the patients presented initially with only distal muscle
      weakness in the lower extremities. The most common mutation was V572L, followed
      by C13S. CONCLUSION: The clinical manifestations of our patients with GNE
      mutations varied. Among twenty-one patients, thirteen patients showed the typical
      GNE myopathy phenotype. There was no relationship between clinical features and
      site of mutation. Therefore, we suggest that neither homozygous nor compound
      heterozygous models are correlated with disease phenotype or disease severity.

PMID- 23549800
TI  - Prevalence and clinical factors of anxiety and depression in neurally mediated
      and unexplained syncope.
AB  - PURPOSE: Several studies have demonstrated that psychiatric disorders such as
      anxiety, depression and panic attack are associated with syncope, especially
      vasovagal and unexplained syncope (US). The aim of this study was to compare the
      prevalence of anxiety and depression between patients with neurally mediated
      syncope (NMS) and US and to investigate the clinical factors associated with
      anxiety and depression. MATERIALS AND METHODS: Between January 2009 and March
      2010, 383 patients with syncopal episodes completed a Hospital Anxiety and
      Depression Scale questionnaire to assess symptoms of anxiety and depression.
      Inclusion criteria were NMS and US. Exclusion criteria were cardiac syncope,
      orthostatic hypotension and other disorders mimicking syncope. After exclusion,
      199 patients were included. RESULTS: There were 176 (88.4%) NMS patients and 23
      (11.6%) US patients. The prevalence of abnormal anxiety and depression were not
      significantly different between the NMS and US groups (10.2% vs. 8.7%, p=0.99;
      8.5% vs. 17.4%, p=0.24). Clinical factors associated with anxiety were female
      gender (p=0.01) and six or more recurrent syncopal episodes (p=0.01) by
      univariate analysis. The only factor associated with abnormal anxiety score
      (OR=20.26, 95% CI: 1.4-291.6, p=0.01) was more than six recurrent syncopal
      episodes, while a positive head-up tilt table testing response was inversely
      associated with abnormal depression score (OR=0.28, CI: 0.08-0.97, p=0.04) in the
      multiple logistic regression analysis. CONCLUSION: Anxiety was associated with
      frequent syncopal episodes. Thus, anxiety might be considered in the management
      of syncope patients.

PMID- 23549801
TI  - Usefulness of an implantable loop recorder in patients with syncope of an unknown
      cause.
AB  - PURPOSE: The mechanisms underlying syncope remain unknown in about 20% of
      patients with recurrent syncope. The implantable loop recorder (ILR) has been
      shown to be a useful diagnostic tool in patients with unexplained syncope even
      after negative initial evaluations. Nevertheless, ILR has rarely been used in
      clinical practice. MATERIALS AND METHODS: This study included 18 consecutive
      patients who had an ILR implanted at our center because of recurrent unexplained
      syncope after extensive diagnostic tests between February 2006 and June 2011.
      RESULTS: Diagnosis was confirmed in 10 (55.6%) of the 18 enrolled patients (13
      males, 61+/-15 years). The confirmed diagnoses included sick sinus syndrome (n=6,
      60%), advanced atrioventricular block (n=2, 20%) and ventricular tachyarrhythmia
      (n=2, 20%). The mean follow-up durations of the total study subjects and the
      diagnosed patients were 11.3+/-10.6 months and 5.6+/-9.2 months, respectively. Of
      the 10 diagnosed patients, 8 (80%) were diagnosed within 6 months of loop
      recorder implantation. CONCLUSION: ILR may be a valuable and effective diagnostic
      tool for patients with unexplained syncope.

PMID- 23549802
TI  - Comparison of early clinical outcomes following transcatheter aortic valve
      implantation versus surgical aortic valve replacement versus optimal medical
      therapy in patients older than 80 years with symptomatic severe aortic stenosis.
AB  - PURPOSE: Transcatheter aortic valve implantation (TAVI) has become an attractive
      therapeutic strategy for severe aortic stenosis (AS) in elderly patients due to
      its minimally-invasive nature. Therefore, early results of its clinical outcomes
      in elderly Korean patients were evaluated. MATERIALS AND METHODS: We compared
      early clinical outcomes of TAVI, surgical aortic valve replacement (SAVR), and
      optimal medical therapy (OMT) in patients aged>=80 years with symptomatic severe
      AS. Treatment groups were allocated as follows: TAVI (n=10), SAVR (n=14), and OMT
      (n=42). RESULTS: Baseline clinical characteristics including predicted operative
      mortality were similar among the three groups. However, patients with New York
      Heart Association functional class III or IV symptoms and smaller aortic valve
      area were treated with TAVI or SAVR rather than OMT. In-hospital combined safety
      endpoints (all-cause mortality, major stroke, peri-procedural myocardial
      infarction, life-threatening bleeding, major vascular complication, and acute
      kidney injury) after TAVI or SAVR were significantly lower in the TAVI group than
      in the SAVR group (10.0% vs. 71.4%, respectively, p=0.005), along with an
      acceptable rate of symptom improvement and device success. During the follow-up
      period, the TAVI group showed the lowest rate of 3-month major adverse
      cardiovascular and cerebrovascular events, a composite of all-cause mortality,
      myocardial infarction, major stroke, and re-hospitalization (TAVI 0.0% vs. SAVR
      50.0% vs. OMT 42.9%, p=0.017). CONCLUSION: Treatment with TAVI was associated
      with lower event rates compared to SAVR or OMT. Therefore, TAVI may be considered
      as the first therapeutic strategy in selected patients aged>=80 years with
      symptomatic severe AS.

PMID- 23549803
TI  - A novel 5'-uncoding region -1248 A>G variation of mitofusin-2 gene is associated
      with hypertension in Chinese.
AB  - PURPOSE: Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is
      very important in the origin and development of hypertension. However, the
      mechanism of Mfn2/HSG expression regulation was not uncovered. This study was
      designed to explore the association of a novel 5'-uncoding region (UCR) -1248 A>G
      variation of HSG/Mfn2 gene and hypertension. MATERIALS AND METHODS: 472 healthy,
      normotensive subjects [normotension (NT) group], 454 prehypertensive subjects
      [prehypertension (PH) group] and 978 hypertensive patients [essential
      hypertension (EH) group] were screened for an association study between 5'-UCR 
      1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA
      sequencing after venous blood was drawn and DNA was extracted. RESULTS: When
      comparing the A and G frequency in EH, PH and NT groups, in total, NT group
      significantly had higher A frequency than in PH group [odds ratio (OR)=1.605,
      confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI
      95%=3.783-7.695, p<0.01). When subgrouped by gender, A frequency in NT group was
      still significantly higher than in EH group (male: OR= 4.264, CI 95%=2.780-6.543,
      p<0.01; female: OR=8.897, CI 95%=4.686-16.891, p<0.01), but not from PH group,
      either in male group or in female group. Ordinal Logistic Regression analysis
      showed that A>G variation was significantly related with blood pressure level (B=
      1.271, Wald=40.914, CI 95%=-1.660 - -0.881, p<0.01). CONCLUSION: 5'-UCR -1248 A>G
      variation of Mfn2/HSG gene was a novel variation and may be associated with
      hypertension in Chinese.

PMID- 23549804
TI  - Is insulin resistance an intrinsic defect in asian polycystic ovary syndrome?
AB  - PURPOSE: Approximately 50% to 70% of women with polycystic ovary syndrome (PCOS)
      have some degree of insulin resistance, and obesity is known to worsen insulin
      resistance. Many metabolic consequences of PCOS are similar to those of obesity;
      therefore, defining the cause of insulin resistance in women can be difficult.
      Our objective was to clarify the factors contributing to insulin resistance in
      PCOS. MATERIALS AND METHODS: We consecutively recruited 144 women with PCOS [age:
      26+/-5 yr, body mass index, body mass index (BMI): 24.4+/-4.0 kg/m2] and 145
      controls (age: 25+/-5 yr, BMI: 23.0+/-3.6 kg/m2), and divided them into
      overweight/obese (ow/ob, BMI>=23 kg/m2) and lean (BMI<23 kg/m2) groups.
      Anthropometric measures and a 75-g oral glucose tolerance test were performed,
      and insulin sensitivity index (ISI) was calculated as an index of insulin
      sensitivity. Factors predictive of ISI were determined using regression analysis.
      RESULTS: ISI was significantly lower in both lean and ow/ob women with PCOS
      compared to BMI-matched controls (p<0.05). Increasing BMI by 1 kg/m2 decreased
      ISI by 0.169 in PCOS patients (p<0.05) and by 0.238 in controls (p<0.05); there
      was no significant difference between these groups. In lean PCOS patients and
      lean controls, BMI had no effect on ISI. Multiple regression analysis revealed
      that PCOS status (beta=-0.423, p<0.001) and BMI (beta=-0.375, p<0.001) were
      significantly associated with ISI. CONCLUSION: Insulin resistance is an intrinsic
      defect of PCOS, and a high BMI could exacerbate insulin resistance in all women,
      irrespective of whether they have PCOS.

PMID- 23549805
TI  - The risk of metabolic syndrome according to the white blood cell count in
      apparently healthy Korean adults.
AB  - PURPOSE: Considerable amount of interest has been focused on the positive
      relationship between inflammation and the metabolic syndrome (MS). However, few
      studies have been performed to evaluate the relationship between baseline white
      blood cell (WBC) count and future risk for developing MS. Therefore, we
      investigated whether the baseline plasma levels of WBC count could be associated
      with future risk for MS in apparently healthy Korean. MATERIALS AND METHODS: A
      total of 1135 subjects (781 men and 354 women with a mean age of 49 years), who
      underwent health examinations at Kangbuk Samsung Hospital in both 2002 and 2005
      were enrolled. The presence of MS was defined using the modified criteria of the
      National Cholesterol Education Program Adult Treatment Panel III using BMI
      instead of waist circumference. RESULTS: The baseline levels of WBC count were
      significantly higher among incident MS cases than among subjects without MS. The
      relative risks of incident MS were 1.4, 3.2 and 2.7 for WBC quartiles 2, 3, and
      4, respectively, when compared with the first quartile (p-value for trend<0.001).
      These positive associations persisted after adjustment for baseline body mass
      index, blood pressure, fasting glucose, high density lipoprotein-cholesterol,
      triglyceride and homeostatic model assessment-insulin resistance; adjusted
      relative risk of incident MS for the 2nd, 3rd and 4th quartile groups vs. the
      lowest quartile were 1.2, 2.4 and 1.7, respectively (p-value for trend=0.011).
      CONCLUSION: This retrospective cohort study suggests that an elevated WBC count
      could be associated with incident MS, suggesting that baseline inflammation
      mirrored by WBC level can impact future MS development.

PMID- 23549806
TI  - Association of monocyte chemoattractant protein-1 (MCP-1) 2518A/G polymorphism
      with proliferative diabetic retinopathy in Korean type 2 diabetes.
AB  - PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that can
      increase adhesion molecule expression on monocytes and produce superoxide anions.
      Hyperglycemia induces MCP-1 production in vascular endothelial cells and retinal
      pigmented epithelial cells, and has been implicated as a causal factor in the
      facilitation of vascular complications in diabetes. In the present study, we
      evaluated the association of a single nucleotide polymorphism (SNP) in the MCP-1
      gene with proliferative diabetic retinopathy (PDR) in a Korean population with
      type 2 diabetes. MATERIALS AND METHODS: We conducted a case-control study, which
      enrolled 590 subjects with type 2 diabetes, and SNP genotyping of c.2518A/G in
      the MCP-1 gene was performed using polymerase chain reaction followed by
      digestion with PvuII restriction enzyme. RESULTS: The prevalence of c.2518A/G
      polymorphism in diabetic patients was 13.2% (A/A), 47.1% (A/G) and 39.7% (G/G).
      In patients with diabetic retinopathy, the prevalence of PDR was significantly
      higher (p=0.009) in diabetic subjects with the c.2518A/A genotype (35.9%; n=78)
      compared to those with either the A/G or G/G genotype (22.3%, n=512). The
      prevalence of any other micro and macro-complications, including nephropathy and
      cerebrovascular events, were not different according to the c.2518A/G genotype.
      CONCLUSION: Our new genetic findings suggest that the c.2518A/A genotype in MCP-1
      could be used as a susceptibility gene to predispose Koreans exhibiting type 2
      diabetes for the development of PDR.

PMID- 23549807
TI  - Relationship between milk and calcium intake and lipid metabolism in female
      patients with type 2 diabetes.
AB  - PURPOSE: This study was conducted to determine the association between intake of
      milk and dairy products as well as calcium and biomarkers related to lipid
      metabolism in Korean female patients with type 2 diabetes. MATERIALS AND METHODS:
      A cohort of 509 female subjects (mean age: 59.0 years; range: 35-80 years) was
      recruited from Huh's Diabetes Clinic in Seoul between 2005 and 2010. Dietary
      intake was assessed using a validated food-frequency questionnaire. Subjects were
      divided into three groups on the basis of their daily intake of milk and dairy
      products [<50 g/day (0<50 g/day), 50-200 g/day, and >200 g/day (>200-1201 g/day)]
      and then further divided into two groups according to their daily calcium intake:
      below and above the estimated average requirement (EAR). RESULTS: After
      adjustment for age, body mass index, energy intake, exercise, use of nutritional
      supplements and cholesterol medication, the level of serum high-density
      lipoprotein (HDL)-cholesterol was significantly higher in subjects with milk and
      dairy products consumption of >200 g/day than in subjects in the other two
      groups. Those subjects with a milk and dairy products consumption of >200 g/day
      had significantly higher levels of apolipoprotein A-1 and a significantly lower
      atherogenic index than the other two groups. Patients with a calcium intake above
      the EAR exhibited a significantly greater serum HDL-cholesterol level than those
      with a calcium intake below the EAR. CONCLUSION: Milk and dairy products, good
      sources of calcium, play a positive role in lipid profiles in female patients
      with type 2 diabetes.

PMID- 23549808
TI  - Effectiveness of an i-PTH measurement in predicting post thyroidectomy
      hypocalcemia: prospective controlled study.
AB  - PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy.
      The purpose of this study was to determine whether measurement of intact
      parathyroid hormone (i-PTH) level in thyroidectomy patients could predict
      hypocalcemia. MATERIALS AND METHODS: We performed a prospective study of patients
      undergoing total thyroidectomy. Serum concentration of i-PTH, total calcium (Ca),
      ionized calcium (Ca2+), phosphate (P), magnesium (Mg), and albumin were measured
      preoperatively and at 0 hour, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours
      postoperatively. RESULTS: 108 patients were recruited to the study. A total of 50
      patients (46%) experienced hypocalcemia. The serum i-PTH concentration was
      linearly related to the time of measurement, while concentrations of P, Mg,
      albumin, Ca, and Ca2+ were not. We compared odds ratios, and found that the
      concentration of i-PTH at 6 hours post operation was the most closely related to
      the occurrence of hypocalcemic symptom. On ROC analysis using i-PTH level at 6
      hours, an i-PTH level of 10.6 mg/dL was found to maximize both sensitivity and
      specificity at the same time point. CONCLUSION: We found that i-PTH was a
      predictor of hypocalcemia, and that the earliest predictor of hypocalcemic
      symptoms was an i-PTH concentration lower than 10.6 mg/dL obtained 6 hours after
      total thyroidectomy.

PMID- 23549809
TI  - Serum CA 19-9 and CEA levels as a prognostic factor in pancreatic adenocarcinoma.
AB  - PURPOSE: To investigate the use of pretreatment carbohydrate antigen (CA) 19-9
      and carcinoembryonic antigen (CEA) as prognostic factors to determine survival in
      pancreatic adenocarcinoma. MATERIALS AND METHODS: A retrospective review of the
      medical records of patients who were diagnosed with pancreatic adenocarcinoma and
      received surgery, chemoradiotherapy or chemotherapy was performed. Factors,
      including CA 19-9 and CEA, associated with the survival of pancreatic cancer
      patients were analyzed. RESULTS: Patients with the median age of 65 years were
      included (n=187). Elevated serum CA 19-9 levels and CEA levels were observed in
      75.4% and 39% of patients at diagnosis, respectively. CEA was correlated with
      tumor stages (p=0.005), but CA 19-9 was not. CA 19-9 and CEA were elevated in
      69.0% and 33.3% of patients with resectable pancreatic cancer, and elevated in
      72.9% and 47.2% of patients with advanced pancreatic cancer, respectively. The
      median overall survival of the normal serum CEA group was longer than that of the
      elevated serum CEA group (16.3 months vs. 10.2 months, p=0.004). However, the
      median overall survival of the normal serum CA 19-9 group was not different from
      that of the elevated serum CA 19-9 group (12.4 months vs. 13.5 months, p=0.969).
      The independent factors associated with overall survival were advanced pancreatic
      cancer [harzard ratio (HR) 4.33, p=0.001] and elevated serum CEA level (HR 1.52,
      p=0.032). CONCLUSION: Patients with elevated serum CEA level at diagnosis
      demonstrated poor overall survival. Pretreatment CEA level may predict the
      prognosis of patients with pancreatic adenocarcinoma.

PMID- 23549810
TI  - ROS1 expression in invasive ductal carcinoma of the breast related to
      proliferation activity.
AB  - PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain
      that has been hypothesized to mediate the effects of early stage tumor
      progression. In addition, it was reported that ROS1 expression was observed in
      diverse cancer tissue or cell lines and ROS1 is associated with the development
      of several tumors. However, ROS1 expression has not been studied in breast cancer
      to date. Therefore, we investigated ROS1 expression at the protein and gene level
      to compare expression patterns and to verify the association with prognostic
      factors in invasive ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS:
      Tissue samples from 203 patients were used. Forty-six cases were available for
      fresh tissue. We performed immunohistochemical staining and real-time polymerase
      chain reaction (PCR). RESULTS: ROS1 expression was significantly lower in
      proportion to higher histologic grade, higher mitotic counts, lower estrogen
      receptor expression, and a higher Ki-67 proliferation index, although ROS1
      expression was not significantly associated with the survival rate. The result of
      real-time PCR revealed similar trends, however not statistically significant.
      CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic
      factors of IDC and its expression in IDC is related to the proliferation of tumor
      cells.

PMID- 23549811
TI  - Relationship between negative mental adjustment to cancer and distress in thyroid
      cancer patients.
AB  - PURPOSE: Previous studies have reported that over a third of cancer patients
      experience significant psychological distress with diagnosis and treatment of
      cancer. Mental adjustment to cancer as well as other biologic and demographic
      factors may be associated with their distress. We investigated the relationship
      between mental adjustment and distress in patients with thyroid cancer prior to
      thyroidectomy. MATERIALS AND METHODS: One hundred and fifty-two thyroid cancer
      patients were included in the final analysis. After global distress levels were
      screened with a distress thermometer, patients were evaluated concerning mental
      adjustment to cancer, as well as demographic and cancer-related characteristics.
      A thyroid function test was also performed. Regression analysis was performed to
      discern significant factors associated with distress in thyroid cancer patients.
      RESULTS: Our regression model was significant and explained 38.5% of the total
      variance in distress of this patient group. Anxious-preoccupation and helpless
      hopeless factors on the mental adjustment to cancer scale were significantly
      associated with distress in thyroid cancer patients. CONCLUSION: Negative
      emotional response to cancer diagnosis may be associated with distress in thyroid
      cancer patients awaiting thyroidectomy. Screening of mental coping strategies at
      the beginning of cancer treatment may predict psychological distress in cancer
      patients. Further studies on the efficacy of psychiatric intervention during
      cancer treatment may be needed for patients showing maladaptive psychological
      responses to cancer.

PMID- 23549812
TI  - Can Western based online prostate cancer risk calculators be used to predict
      prostate cancer after prostate biopsy for the Korean population?
AB  - PURPOSE: To access the predictive value of the European Randomized Screening of
      Prostate Cancer Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention
      Trial Risk Calculator (PCPT-RC) in the Korean population. MATERIALS AND METHODS:
      We retrospectively analyzed the data of 517 men who underwent transrectal
      ultrasound guided prostate biopsy between January 2008 and November 2010. Simple
      and multiple logistic regression analysis were performed to compare the result of
      prostate biopsy. Area under the receiver operating characteristics curves (AUC
      ROC) and calibration plots were prepared for further analysis to compare the risk
      calculators and other clinical variables. RESULTS: Prostate cancer was diagnosed
      in 125 (24.1%) men. For prostate cancer prediction, the area under curve (AUC) of
      the ERSPC-RC was 77.4%. This result was significantly greater than the AUCs of
      the PCPT-RC and the prostate-specific antigen (PSA) (64.5% and 64.1%,
      respectively, p<0.01), but not significantly different from the AUC of the PSA
      density (PSAD) (76.1%, p=0.540). When the results of the calibration plots were
      compared, the ERSPC-RC plot was more constant than that of PSAD. CONCLUSION: The
      ERSPC-RC was better than PCPT-RC and PSA in predicting prostate cancer risk in
      the present study. However, the difference in performance between the ERSPC-RC
      and PSAD was not significant. Therefore, the Western based prostate cancer risk
      calculators are not useful for urologists in predicting prostate cancer in the
      Korean population.

PMID- 23549813
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration for the
      diagnosis of central lung parenchymal lesions.
AB  - PURPOSE: The purpose of this study was to evaluate the usefulness of convex probe
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for
      detecting malignancy in parenchymal pulmonary lesions located adjacent to the
      central airways. MATERIALS AND METHODS: We retrospectively reviewed the
      diagnostic performance of EBUS-TBNA in consecutive patients with high clinical
      suspicion of a centrally located primary lung cancer who had undergone EBUS-TBNA
      at the Samsung Medical Center between May 2009 and June 2011. RESULTS: Thirty
      seven patients underwent EBUS-TBNA for intrapulmonary lesions adjacent to the
      central airways. Seven lesions were located adjacent to the trachea and 30
      lesions were located adjacent to the bronchi. Cytologic and histologic samples
      obtained via EBUS-TBNA were diagnostic in 32 of 37 (86.4%) of patients. The final
      diagnosis was lung cancer in 30 patients (7 small cell lung cancer, 23 non-small
      cell lung cancer), lymphoma in one and malignant fibrous histiocytoma in one
      patient. The diagnostic sensitivity of EBUS-TBNA in detecting malignancy and
      detecting both malignancy and benignity was 91.4% and 86.5%, respectively. Two
      patients experienced minor complications. CONCLUSION: EBUS-TBNA is an effective
      and safe method for tissue diagnosis of parenchymal lesions that lie centrally
      close to the airways. EBUS-TBNA should be considered the procedure of choice for
      patients with centrally located lesions without endobronchial involvement.

PMID- 23549814
TI  - Cholesterol depletion in cell membranes of human airway epithelial cells
      suppresses MUC5AC gene expression.
AB  - PURPOSE: If cholesterol in the cell membrane is depleted by treating cells with
      methyl-beta-cyclodextrin (MbetaCD), the activities of transmembrane receptors are
      altered in a cell-specific and/or receptor-specific manner. The proinflammatory
      cytokines, IL-1beta is potent inducers of MUC5AC mRNA and protein synthesis in
      human airway epithelial cells. Cells activated by IL-1beta showed increased
      phosphorylation of extracellular signal regulated kinase (ERK) and p38 mitogen
      activated protein kinase (MAPK). Thus, we investigated the effects of cholesterol
      depletion on the expression of MUC5AC in human airway epithelial cells and
      whether these alterations to MUC5AC expression were related to MAPK activity.
      MATERIALS AND METHODS: After NCI-H292 cells were pretreated with 1% MbetaCD
      before adding IL-1beta for 24 hours, MUC5AC mRNA expression was determined by
      reverse transcription- polymerase chain reaction (RT-PCR) and real time-PCR.
      Cholesterol depletion by MbetaCD was measured by modified microenzymatic
      fluorescence assay and filipin staining. The phosphorylation of IL-1 receptor,
      ERK and p38 MAPK, was analyzed by western blot. RESULTS: Cholesterol in the cell
      membrane was significantly depleted by treatment with MbetaCD on cells. IL-1beta
      induced MUC5AC mRNA expression was decreased by MbetaCD and this decrease
      occurred IL-1-receptor- specifically. Moreover, we have shown that MbetaCD
      suppressed the activation of ERK1/2 and p38 MAPK in cells activated with IL
      1beta. This result suggests that MbetaCD-mediated suppression of IL-1beta-induced
      MUC5AC mRNA operated via the ERK- and p38 MAPK-dependent pathway. CONCLUSION:
      Cholesterol depletion in NCI-H292 cell membrane may be considered an anti
      hypersecretory method since it effectively inhibits mucus secretion of
      respiratory epithelial cells.

PMID- 23549815
TI  - Studies on therapeutic effects and pathological features of an antithrombin
      preparation in septic disseminated intravascular coagulation patients.
AB  - PURPOSE: Few reports have been made on the therapeutic effects as well as
      pathological features of an antithrombin preparation in patients diagnosed with
      septic disseminated intravascular coagulation (DIC) by the diagnostic criteria
      for acute DIC. MATERIALS AND METHODS: A total of 88 sepsis patients who had
      received inpatient hospital care during the period from January 2000 through
      December 2008 were divided into two groups, an antithrombin group and a non
      antithrombin group, to study the outcomes. Furthermore, the relationship between
      sepsis-related factors and DIC in 44 patients was studied. RESULTS: The
      antithrombin group contained 34 patients, and the non-antithrombin group
      contained 54 patients. The outcomes were significantly better in the antithrombin
      group. The levels of protein C were low in DIC patients. CONCLUSION: Our results
      suggest that early administration of antithrombin might improve outcomes of
      septic DIC patients in the diagnostic criteria for Japanese Association for Acute
      Medicine acute DIC.

PMID- 23549816
TI  - The Studer orthotopic neobladder: long-term (more than 10 years) functional
      outcomes, urodynamic features, and complications.
AB  - PURPOSE: Radical cystectomy and urinary diversion are the standard treatment for
      invasive bladder cancer. We analyzed the long-term (>10 years postoperatively)
      functional outcomes, complications, and urodynamic findings in a single center
      series of patients who underwent cystectomy and a Studer ileal neobladder
      substitution. MATERIALS AND METHODS: A retrospective chart review of 108 Studer
      pouches constructed during 1990 and 2011 was performed. Data were analyzed in
      terms of long-term (>10 years) outcomes. Complications, incontinence, voiding
      difficulties, upper urinary tract changes, overall satisfaction, and urodynamic
      findings of the reservoir were obtained. RESULTS: We evaluated 19 out of 50
      patients who had lived for over 10 years postoperatively. Another 31 patients
      were not traced: 7 patients died following recurrence, 15 died due to
      exacerbation of a comorbidity, and 9 patients were lost to follow-up. Concerning
      complications, 6 patients had an atrophied kidney, 5 patients had moderate
      hydronephrosis, 5 patients had chronic recurrence of pylelonephritis, and 2
      patients had voiding difficulty because of bladder neck stricture due to clean
      intermittent catheterization. One patient underwent an operation due to
      intestinal obstruction. Seven patients had incontinence; all 7 patients showed
      intermittently at night and 2 patients even in waking hours. Maximum bladder
      capacity was 484.1+/-119.2 mL, maximum flow rate was 13.6+/-9.7 mL/sec, and post
      void residual urine volume was 146.8+/-82.7 mL. CONCLUSION: Long-term outcomes
      with the Studer orthotopic ileal neobladder have an acceptable complication rate
      and good functional results. However, potential adverse outcomes such as renal
      deterioration, dysfunctional voiding should also be considered.

PMID- 23549817
TI  - Non-oliguric hyperkalemia in extremely low birth weight infants.
AB  - PURPOSE: It is to examine clinical manifestations, early biochemical indicators,
      and risk factors for non-oliguric hyperkalemia (NOHK) in extremely low birth
      weight infants (ELBWI). MATERIALS AND METHODS: We collected clinical and
      biochemical data from 75 ELBWI admitted to Ajou University Hospital between Jan.
      2008 and Jun. 2011 by reviewing medical records retrospectively. NOHK was defined
      as serum potassium>=7 mmol/L during the first 72 hours of life with urine
      output>=1 mL/kg/h. RESULTS: NOHK developed in 26.7% (20/75) of ELBWI. Among NOHK
      developed in ELBWI, 85% (17/20) developed within postnatal (PN) 48 hours, 5%
      (1/20) experienced cardiac arrhythmia and 20% (4/20) of NOHK infants expired
      within PN 72 hours. There were statistically significant differences in
      gestational age, use of antenatal steroid, and serum phosphorous level at PN 24
      hours, and serum sodium, calcium, and urea levels at PN 72 hours between NOHK and
      non-NOHK groups (p-value<0.050). However, there were no statistical differences
      in the rate of intraventricular hemorrhage, arrhythmia, mortality occurred,
      methods of fluid therapy, supplementation of amino acid and calcium, frequencies
      of umbilical artery catheterization and urine output between the two groups.
      CONCLUSION: NOHK is not a rare complication in ELBWI. It occurs more frequently
      in ELBWI with younger gestational age and who didn't use antenatal steroid.
      Furthermore, electrolyte imbalance such as hypernatremia, hypocalcemia and
      hyperphosphatemia occurred more often in NOHK group within PN 72 hours.
      Therefore, more use of antenatal steroid and careful control by monitoring
      electrolyte imbalance should be considered in order to prevent NOHK in ELBWI.

PMID- 23549818
TI  - Reversible infertility associated with testosterone therapy for symptomatic
      hypogonadism in infertile couple.
AB  - PURPOSE: Androgen replacement therapy has been shown to be safe and effective for
      most patients with testosterone deficiency. Male partners of infertile couples
      often report significantly poorer sexual activity and complain androgen
      deficiency symptoms. We report herein an adverse effect on fertility caused by
      misusage of androgen replacement therapy in infertile men with hypogonadal
      symptoms. MATERIALS AND METHODS: The study population consisted of 8 male
      patients referred from a local clinic for azoospermia or severe oligozoospermia
      between January 2008 and July 2011. After detailed evaluation at our andrology
      clinic, all patients were diagnosed with iatrogenic hypogonadism associated with
      external androgen replacement. We evaluated changes in semen parameters and serum
      hormone level, and fertility status. RESULTS: All patients had received multiple
      testosterone undecanoate (NebidoR) injections at local clinic due to androgen
      deficiency symptoms combined with lower serum testosterone level. The median
      duration of androgen replacement therapy prior to the development of azoospermia
      was 8 months (range: 4-12 months). After withdrawal of androgen therapy, sperm
      concentration and serum follicle-stimulating hormone level returned to normal
      range at a median 8.5 months (range: 7-10 months). CONCLUSION: Misusage of
      external androgen replacement therapy in infertile men with poor sexual function
      can cause temporary spermatogenic dysfunction, thus aggravating infertility.

PMID- 23549819
TI  - Kinetics of IFN-gamma and TNF-alpha gene expression and their relationship with
      disease progression after infection with Mycobacterium tuberculosis in guinea
      pigs.
AB  - PURPOSE: Guinea pig is one of the most suitable animal models for Mycobacterium
      tuberculosis (M. tb) infection since it shows similarities to pulmonary infection
      in humans. Although guinea pig shows hematogenous spread of M. tb infection into
      the whole body, immunological studies have mainly focused on granulomatous
      tissues in lungs and spleens. In order to investigate the time-course of disease
      pathogenesis and immunological profiles in each infected organ, we performed the
      following approaches with guinea pigs experimentally infected with M. tb over a
      22-week post-infection period. MATERIALS AND METHODS: We examined body weight
      changes, M. tb growth curve, cytokine gene expression (IFN-gamma and TNF-alpha),
      and histopathology in liver, spleen, lungs and lymph nodes of infected guinea
      pigs. RESULTS: The body weights of infected guinea pigs did not increase as much
      as uninfected ones and the number of M. tb bacilli in their organs increased
      except bronchotracheal lymph node during the experimental period. The gene
      expression of IFN-gamma and TNF-alpha was induced between 3 and 6 weeks of
      infection; however, kinetic profiles of cytokine gene expression showed
      heterogeneity among organs over the study period. Histophathologically
      granulomatous lesions were developed in all four organs of infected guinea pigs.
      CONCLUSION: Although IFN-gamma and TNF-alpha gene expression profiles showed
      heterogeneity, the granuloma formation was clearly observed in every organ
      regardless of whether the number of bacilli increased or decreased. However, this
      protective immunity was accompanied with severe tissue damage in all four organs,
      which may lead to the death of guinea pigs.

PMID- 23549820
TI  - Neurologic recovery according to the spinal fracture patterns by Denis
      classification.
AB  - PURPOSE: Although Denis classification is considered as one of most clinically
      useful schemes for the evaluation of spinal fracture, there is little
      documentation on the relationship between fracture pattern and the neurologic
      recovery. The purpose is to evaluate the correlation between the fracture
      patterns according to Denis classification and neurologic recovery. MATERIALS AND
      METHODS: The 38 patients (26 men and 12 women) in this series had an average
      follow-up of 47.1 months, and they were all managed surgically. Denis
      classification had been used prospectively to determine the fracture morphology.
      Frankel Scale and American Spinal Injury Association Spinal Cord Injury
      Assessment Form [American Spinal Injury Association (ASIA) score] were obtained
      before surgery, after surgery and at the final follow-up. RESULTS: The common
      injuries making neurologic deterioration were burst fracture and fracture
      dislocation. The degree of neurologic deficits seen first and at the final follow
      up was more severe in fracture-dislocation than burst fracture. The neurologic
      recovery was not different between burst fracture and fracture-dislocation,
      assessed by Frankel grading and ASIA scoring system. The neurologic recovery
      evaluated by ASIA score was not different between the lumbar and thoracic spinal
      fracture. The neurologic recovery assessed by Frankel grade was greater in the
      lumbar spinal fractures in than the thoracic spinal fractures. CONCLUSION: The
      severity of initial and the final follow-up neurologic deficits were correlated
      with the fracture patterns according to Denis classification, but the neurologic
      recovery was not correlated.

PMID- 23549821
TI  - Locking plate in proximal tibial fracture: a correlation between the coronal
      alignment of tibia and joint screw angle.
AB  - PURPOSE: The purpose of this study is to evaluate the relationship between the
      angle formed between the proximal most screw through the locking compression
      plate-proximal lateral tibia (LCP PLT) and the joint line, and to evaluate if
      this angle can be used intraoperatively as an assessment tool to determine normal
      alignment of the tibia in the coronal plane. MATERIALS AND METHODS: There are two
      parts to this study: in the first part, LCP PLT was applied to 30 cadaveric adult
      tibia. The angle between the joint line and the proximal most screw was measured
      and termed as the 'joint screw angle' (JSA). In the second part, 56 proximal
      tibial fractures treated with LCP PLT were retrospectively studied. Two angles
      were measured on the radiographs, the medial proximal tibial angle (MPTA) and the
      JSA. Their relationship was analyzed statistically. RESULTS: The average JSA was
      1.16 degrees in the anatomical study. Statistical analysis of the clinical study
      showed that the normal MPTA had a direct correlation with an acceptable JSA.
      CONCLUSION: We therefore conclude that the JSA can be used intraoperatively to
      assess the achievement of a normal coronal axis.

PMID- 23549822
TI  - Loss of lordosis and clinical outcomes after anterior cervical fusion with
      dynamic rotational plates.
AB  - PURPOSE: The cervical dynamic rotational plating system may induce bone graft
      subsidence, so it may cause loss of cervical lordosis. However there were few
      studies for alignments of cervical spines influencing the clinical results after
      using dynamic rotational plates. The purpose is to evaluate the effect of graft
      subsidence on cervical alignments due to the dynamic rotational cervical plates
      and correlating it with the clinical outcomes of patients undergoing anterior
      cervical fusion. MATERIALS AND METHODS: Thirty-three patients with disease or
      fracture underwent anterior cervical decompression and fusion using a dynamic
      rotational plate. The presence and extent of implant complications, graft
      subsidence, loss of lordosis were identified and Visual Analog Scale score (VAS
      score), Japanese Orthopaedic Association score (JOA score), clinical outcomes
      based on Odom's criteria were recorded. RESULTS: Fusion was achieved without
      implant complications in all cases. The mean graft subsidence at 6 months after
      the surgery was 1.46 mm. The lordotic changes in local cervical angles were 5.85
      degrees  which was obtained postoperatively. VAS score for radicular pain was
      improved by 5.19 and the JOA score was improved by 3. Clinical outcomes based on
      Odom's criteria showed sixteen excellent, ten good and two satisfactory results.
      There was no significant relationship between clinical outcomes and changes in
      the cervical angles. CONCLUSION: Dynamic rotational anterior cervical plating
      provides comparable clinical outcomes to that of the reports of former static
      cervical platings. The loss of lordosis is related to the amount of graft
      settling but it is not related to the clinical outcomes.

PMID- 23549823
TI  - Comparison of emergence time in children undergoing minor surgery according to
      anesthetic: desflurane and sevoflurane.
AB  - PURPOSE: In earlier analyses, desflurane has been shown to reduce average
      extubation time and the variability of extubation time by 20% to 25% relative to
      sevoflurane in adult patients. We undertook this study to determine which agents
      prompt less recovery time in pediatric patients undergoing minor surgery.
      MATERIALS AND METHODS: After obtaining Institutional Review Board approval, we
      retrospectively reviewed the anesthesia records of 499 patients, with an average
      age of 5 years, who underwent minor surgeries at Severance Eye and Ear, Nose and
      Throat Hospital between May 2010 and April 2011. Anesthesia was induced with
      propofol and rocuronium. Anesthesia was maintained with sevoflurane (n=340) or
      desflurane (n=159) with 50% air/O2. Time from cessation of anesthetics to
      recovery of self-respiration, eye opening on verbal command and extubation were
      compared between the two groups. Additionally, the incidences of postoperative
      respiratory adverse events were also compared. RESULTS: Times to self-respiration
      recovery, eye opening on verbal command, and extubation were significantly faster
      in the desflurane group than the sevoflurane group (4.6+/-2.5 min vs. 6.9+/-3.8
      min, 6.6+/-3.0 min vs. 9.2+/-3.6 min, and 6.2+/-2.7 min vs. 9.3+/-3.7 min,
      respectively, p<0.005). There were no statistically significant differences
      between the two groups with respect to adverse respiratory events during the peri
      operative period (38.2% vs. 34.6%, p=0.468). CONCLUSION: Emergence and recovery
      from anesthesia were significantly faster in the desflurane group of children
      undergoing minor surgery. Desflurane did not result in any differences in
      respiratory adverse events during recovery compared to sevoflurane.

PMID- 23549825
TI  - Laryngeal mask airway insertion in adults: comparison between fully deflated and
      partially inflated technique.
AB  - PURPOSE: The laryngeal mask airway (LMA) is a supraglottic airway device designed
      to seal around the laryngeal inlet. A controlled study was designed to compare
      the effectiveness and complications in inserting the LMA when the cuff is fully
      deflated and partially inflated. MATERIALS AND METHODS: American Society of
      Anesthesiologists physical status I or II 172 female patients scheduled for
      gynecologic procedures were included in this study. Patients were randomly
      allocated into one of the two groups; fully deflated (n=86) and partially
      inflated group (n=86). A size #4 LMA was inserted. The number of attempts, time
      taken for successful insertion, grade of leak, grade of fiberoptic view, and
      complications were evaluated. RESULTS: All 172 patients completed the study
      protocol. The number of attempts, time taken for successful insertion, and grade
      of leak were not significantly different between the two groups. The grade of
      fiberoptic view and complications were lower in the fully deflated group.
      CONCLUSION: The fully deflated method is more accurate and safe because of better
      fiberoptic view and lesser complications than the partially inflated group.

PMID- 23549824
TI  - Effect-site concentration of remifentanil for minimizing cardiovascular changes
      by inhalation of desflurane.
AB  - PURPOSE: This study aims to investigate the most appropriate effect-site
      concentration of remifentanil to minimize cardiovascular changes during
      inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine
      American Society of Anesthesiologists physical status class I patients aged 20-65
      years were randomly allocated into one of three groups. Anesthesia was induced
      with etomidate and rocuronium. Remifentanil was infused at effect-site
      concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After
      target concentrations of remifentanil were reached, desflurane was inhaled to
      maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5
      minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic
      blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal
      concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal
      concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP
      and HR within group R4 were not significantly different as compared with baseline
      values. However, measured parameters within group R2 increased significantly 1-3
      minutes after desflurane inhalation. The MAP within group R6 decreased
      significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant
      differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after
      inhalation (p<0.05). The incidence of side effects such as hyper- or hypo
      tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in
      group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site
      concentration of remifentanil for blunting hemodynamic responses by inhalation of
      high concentration desflurane is 4 ng/mL.

PMID- 23549826
TI  - Fresh frozen plasma in pump priming for congenital heart surgery: evaluation of
      effects on postoperative coagulation profiles using a fibrinogen assay and
      rotational thromboelastometry.
AB  - PURPOSE: In this prospective study, the effects of fresh frozen plasma (FFP)
      included in pump priming for congenital heart surgery in infants and children on
      post-bypass coagulation profiles were evaluated. MATERIALS AND METHODS: Either
      20% albumin (50-100 mL) or FFP (1-2 units) was added to pump priming for patients
      randomly allocated into control or treatment groups, respectively. Hematologic
      assays, including functional fibrinogen level, and rotational thromboelastometry
      (ROTEM(r)) were measured before skin incision (baseline), after weaning from
      cardiopulmonary bypass (CPB) and heparin reversal, and at 24 hours (h) in the
      intensive care unit (ICU). RESULTS: All the baseline measurements were comparable
      between the control and treatment groups of infants and children. After heparin
      reversal, however, significantly higher fibrinogen levels and less reduced ROTEM
      parameters, which reflect clot formation and firmness, were demonstrated in the
      treatment groups of infants and children. At 24 h in the ICU, hematologic assays
      and ROTEM measurements were comparable between the control and treatment groups
      of infants and children. Transfusion requirements, excluding FFP in pump prime,
      and postoperative bleeding were comparable between the control and treatment
      groups of infants and children. CONCLUSION: Although clinical benefits were not
      clearly found, the inclusion of FFP in pump priming for congenital heart surgery
      in infants and children was shown to improve the hemodilution-related hemostatic
      dysfunction immediately after weaning from CPB and heparin reversal.

PMID- 23549828
TI  - Human SNF2L gene is regulated constitutively and inducibly in neural cells via a
      cAMP-response element.
AB  - PURPOSE: SNF2L belongs to Imitation Switch family and plays an essential role in
      neural tissues and gonads. In our previous studies, we have demonstrated that the
      basal transcription of human SNF2L gene is regulated by two cis-elements, cAMP
      response element (CRE)- and Sp1-binding sites. Recent studies suggested that
      cyclic adenosine monophosphate (cAMP) stimulation significantly up-regulated
      SNF2L expression in ovarian granulose cells. These data suggested that protein
      kinase-mediated signal pathways might also regulate SNF2L expression in neural
      cells. We therefore investigated the effects of agents that activate protein
      kinases A on SNF2L gene expression in neural cells. MATERIALS AND METHODS: To
      increase intracellular cAMP levels, all neural cells were treated with forskolin
      and dbcAMP, two cAMP response activators. We exmined the effects of cAMP on the
      promoter activity of human SNF2L gene by luciferase reporter gene assays, and
      further examined the effects of cAMP on endogenous SNF2L mRNA levels by qPCR.
      RESULTS: Transient expression of a luciferase fusion gene under the control of
      the SNF2L promoter was significantly increased by treatment of rat primary
      neurons with forskolin or dbcAMP, but not PC12, C6 and SH-SY5Y cells.
      Consistently, treatment with forskolin or dbcAMP could enhance endogenous SNF2L
      mRNA levels also only in rat primary neurons. CONCLUSION: These results suggest
      that the CRE consensus sequence in the SNF2L proximal promoter most likely
      confers constitutive activation and regulation by cAMP in neural cells.

PMID- 23549827
TI  - Effects of co-administration of intrathecal nociceptin/orphanin FQ and opioid
      antagonists on formalin-induced pain in rats.
AB  - PURPOSE: Nociceptin/orphanin FQ (N/OFQ) as an endogeneous hexadecapeptide is
      known to exert antinociceptive effects spinally. The aims of this study were to
      demonstrate the antinociceptive effects of i.t. N/OFQ and to investigate the
      possible interaction between N/OFQ and endogenous opioid systems using selective
      opioid receptor antagonists in rat formalin tests. MATERIALS AND METHODS: I.t.
      N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to
      a 50 MUL injection of 5% formalin into the right hindpaw of rats. Flinching
      responses were measured from 0-10 min (phase I, an initial acute state) and 11-60
      min (phase II, a prolonged tonic state). To observe which opioid receptors are
      involved in the anti-nociceptive effect of i.t. N/OFQ in the rat-formalin tests,
      naltrindole (5-20 nmol), beta-funaltrexamine (1-10 nmol), and norbinaltorphimine
      (10 nmol), selective delta-, MU- and kappa-opioid receptor antagonists,
      respectively, were administered intrathecally 5 min after i.t. N/OFQ. RESULTS:
      I.t. N/OFQ attenuated the formalin-induced flinching responses in a dose
      dependent manner in both phases I and II. I.t. administration of naltrindole and
      beta-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of
      flinching responses in both phases; however, norbinaltorphimine did not.
      CONCLUSION: I.t. N/OFQ exerted an antinociceptive effect in both phases of the
      rat-formalin test through the nociceptin opioid peptide receptor. In addition,
      the results suggested that delta- and MU-opioid receptors, but not kappa-opioid
      receptors, are involved in the antinociceptive effects of N/OFQ in the spinal
      cord of rats.

PMID- 23549829
TI  - Female longitudinal anal muscles or conjoint longitudinal coats extend into the
      subcutaneous tissue along the vaginal vestibule: a histological study using human
      fetuses.
AB  - PURPOSE: It is still unclear whether the longitudinal anal muscles or conjoint
      longitudinal coats (CLCs) are attached to the vagina, although such an
      attachment, if present, would appear to make an important contribution to the
      integrated supportive system of the female pelvic floor. MATERIALS AND METHODS:
      Using immunohistochemistry for smooth muscle actin, we examined semiserial
      frontal sections of 1) eleven female late-stage fetuses at 28-37 weeks of
      gestation, 2) two female middle-stage fetus (2 specimens at 13 weeks), and, 3)
      six male fetuses at 12 and 37 weeks as a comparison of the morphology. RESULTS:
      In late-stage female fetuses, the CLCs consistently (11/11) extended into the
      subcutaneous tissue along the vaginal vestibule on the anterior side of the
      external anal sphincter. Lateral to the CLCs, the external anal sphincter also
      extended anteriorly toward the vaginal side walls. The anterior part of the CLCs
      originated from the perimysium of the levator ani muscle without any contribution
      of the rectal longitudinal muscle layer. However, in 2 female middle-stage
      fetuses, smooth muscles along the vestibulum extended superiorly toward the
      levetor ani sling. In male fetuses, the CLCs were separated from another
      subcutaneous smooth muscle along the scrotal raphe (posterior parts of the dartos
      layer) by fatty tissue. CONCLUSION: In terms of topographical anatomy, the female
      anterior CLCs are likely to correspond to the lateral extension of the perineal
      body (a bulky subcutaneous smooth muscle mass present in adult women), supporting
      the vaginal vestibule by transmission of force from the levator ani.

PMID- 23549830
TI  - Characteristics of corticospinal tract area according to pontine level.
AB  - Diffusion tensor imaging (DTI) allows to isolate the corticospinal tract (CST)
      area from adjacent structures. Using DTI, we investigated the characteristics of
      the CST areas according to the pontine level in the normal human brain. We
      recruited 33 healthy subjects and DTIs were acquired using a sensitivity-encoding
      head coil on a 1.5-T Philips Gyroscan Intera. We measured the size and fractional
      anisotropy (FA) value of the CST area at the upper, middle, and lower pons. The
      size of the CST area in the lower pons was smaller than those of the mid-pons and
      upper pons, and the size of the CST area in the mid-pons was smallerthan that of
      the upper pons (p<0.05). FA values of the lower pons were larger than those of
      the mid-pons and upper pons, and the FA value of the mid-pons was also larger
      than that of the upper pons (p<0.05). In summary, we found a smaller size and
      higher FA value of the CST area from rostral to caudal direction in the pons.
      These results suggest a more compact neural structure of CST areas from rostral
      to caudal direction in the pons.

PMID- 23549831
TI  - Cardiac tamponade complicated by acupuncture: hemopericardium due to shredded
      coronary artery injury.
AB  - We report a case of 62-year-old man with cardiac tamponade due to coronary artery
      injury after acupuncture into the substernum. After resuscitation of cardiac
      arrest, we performed emergent pericardiocentesis. Nevertheless, the cardiac
      arrest recurred, and the emergent operation on cardiopulmonary bypass was
      performed. We identified hemopericardium due to shredded acute marginal branch of
      right coronary artery, and it was ligated leading to termination of bleeding. The
      patient was discharged without any other complications.

PMID- 23549832
TI  - Primary central nervous system ALK positive anaplastic large cell lymphoma with
      predominantly leptomeningeal involvement in an adult.
AB  - A 31-year-old Korean male presented with altered consciousness and severe
      headache. Brain MRI delineated focal leptomeningeal enhancement without any
      intracerebral lesions. Diagnosis was made based on a brain biopsy showing
      anaplastic large cell lymphoma (ALCL), immunohistochemical stains revealing
      positivity for anaplastic lymphoma kinase (ALK) and an absence of involvement in
      any other organs; specifically, the primary central nervous system ALK+ALCL.
      Complete remission was achieved following 5 cycles of systemic chemotherapy with
      a high dose of Methotrexate and a simultaneous 7 cycles of intrathecal triple
      chemotherapy. Diagnosis of primary leptomeningeal ALK+ALCL is challenging given
      its rarity and non-specific symptoms along with non-pathognomonic radiologic
      findings. We present the first case of primary leptomeningeal ALK-positive ALCL
      where the clinical course, pathologic characteristics and treatment modality are
      described as well as a review of literature.

PMID- 23549833
TI  - Hypermagnesemia accompanied with colonic perforation in a hemodialysis patient.
AB  - We report a case of a chronic hemodialysis patient who developed hypermagnesemia
      due to an overdose of magnesium-containing laxative and paralytic ileus resulting
      in colonic perforation. Despite intravenous calcium infusion and daily
      hemodialysis, the patient developed ischemic colitis and intestinal perforation.
      Colonic perforation accompanied with hypermagnesemia in hemodialysis patients has
      rarely been reported. This case suggests that hypermagnesemia should be
      considered in renal failure patients as this can result in life-threatening
      events despite prompt treatment.

PMID- 23549834
TI  - Extensive bullous complication associated with intermittent pneumatic
      compression.
AB  - Intermittent pneumatic compression (IPC) device is an effective method to prevent
      deep vein thrombosis. This method has been known to be safe with very low rate of
      complications compared to medical thromboprophylaxis. Therefore, this modality
      has been used widely in patients who underwent a hip fracture surgery. We report
      a patient who developed extensive bullae, a potentially serious skin
      complication, beneath the leg sleeves during the use of IPC device after hip
      fracture surgery.

PMID- 23549835
TI  - False femoral neck fracture detected during shaft nailing: a Mach band effect.
AB  - Femoral neck fractures are associated with femoral shaft fractures in 1% to 9% of
      cases. Undisplaced neck fractures are susceptible to displacement during shaft
      nailing. We report the case of a 57-year-old male patient in whom we performed
      standard intramedullary nailing for a femoral shaft fracture. In doing so, we
      identified a vertical radiolucent line at the femoral neck, which was thought to
      be further displacement of a hidden silent fracture or an iatrogenic fracture
      that developed during nail insertion. Consequently, we decided to switch to
      reconstructive femoral nailing. Postoperative hip imaging failed to show the
      femoral neck fracture that we saw in the operating room. Here, we discuss the
      aforementioned case and review the literature concerning this artifact.

PMID- 23549838
TI  - Acoustic characterization of ultrasonic vocalizations by a nocturnal primate
      Tarsius syrichta.
AB  - This preliminary study characterizes the ultrasonic vocalizations produced by
      Philippine tarsiers, Tarsius syrichta. Data were collected at the Philippine
      Tarsier Foundation Sanctuary in Corella, Bohol, Philippines, from July through
      October 2010. Recordings were made on a Wildlife Acoustics Ultrasonic Song Meter
      2 BAT from 29 wild, free-living adult resident T. syrichta (23 females and six
      males). A total of 10,309 USVs were recorded. These vocalizations fell into three
      main categories: chirps, twitters, and whistles. Chirps were the most frequent,
      followed by twitters and whistles. Whereas chirps and twitters were emitted by
      both male and female Philippine tarsiers, whistles were only emitted by adult
      males. Given that vocalizations reported in this study were exclusively recorded
      during capture and handling, it is very likely that these vocalizations function
      as distress calls. However, as the long whistle was only given by adult males who
      were captured at the same time as the female or the group's infant, the function
      of the long whistle might be slightly different than the function of the other
      relatively lower-frequency USVs. 

PMID- 23549837
TI  - Matrine suppresses expression of adhesion molecules and chemokines as a mechanism
      underlying its therapeutic effect in CNS autoimmunity.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a classical experimental model
      of multiple sclerosis (MS), an autoimmune disease of the central nervous system
      (CNS). Previous reports have suggested that matrine (MAT), a quinolizidine
      alkaloid derived from the herb Radix Sophorae Flave, could inhibit clinical EAE,
      but its mechanism of action is not clear. Our present study showed that MAT
      treatment resulted in dose-dependent reduction in neurological scores. Consistent
      with this observation, infiltration of inflammatory cells and demyelination in
      the CNS were also significantly suppressed. We further studied the mechanism
      underlying these effects of MAT by determining whether this treatment influences
      expression of molecules that are involved in the activation and migration of
      inflammatory cells. Our results showed that MAT significantly inhibited
      expression and production in the CNS of ICAM-1 and VCAM-1, key adhesive
      molecules, and CCL3 and CCL5, key chemokines, that attract inflammatory cells
      into the CNS. Furthermore, the TLR4/MD2 pathway, which plays an important role in
      the induction of Th1/Th17 cells in EAE, was also significantly inhibited.
      Together, our study not only demonstrates that MAT may be a novel therapeutic
      option for the treatment for MS, but also provides further information on
      mechanisms underlying the effect of MAT treatment.

PMID- 23549839
TI  - [Video game and internet addiction. The current state of research].
AB  - The use of interactive screen media is widespread and for some users leads to
      pathological symptoms that are phenomenologically similar to signs of addictive
      disorders. Addictive use of computer games and other Internet applications, such
      as social media can be distinguished. In the past standard criteria to classify
      this new disorder were lacking. In DSM-5, nine criteria are proposed for
      diagnosing Internet gaming disorder. The focus is currently on video games as
      most studies have been done in this field. Prevalence estimations are difficult
      to interpret due to the lack of standard diagnostic measures and result in a
      range of the frequency of Internet addiction between 1 % and 4.2 % in the general
      German population. Rates are higher in younger individuals. For computer game
      addiction prevalence rates between 0.9 % and 1.7  % can be found in adolescents.
      Despite substantial comorbidity among those affected current research points to
      addictive media use as a stand-alone disorder.

PMID- 23549840
TI  - Dasatinib: a guide to its use in chronic myeloid leukemia in the EU.
AB  - Oral dasatinib (Sprycel((r))) is effective in the treatment of patients with
      newly diagnosed chronic-phase chronic myeloid leukemia (CML) or imatinib
      resistant or imatinib-intolerant chronic-phase, accelerated-phase, or blast-phase
      CML. In particular, dasatinib is associated with better and faster responses than
      imatinib in patients with newly diagnosed chronic-phase CML. The response to
      dasatinib appears to be maintained in the longer-term. Dasatinib has an
      acceptable tolerability profile; it is associated with myelosuppression, with
      fluid retention being the most common nonhematologic adverse event. Thus,
      dasatinib is a highly effective, once-daily therapy for the first-line treatment
      of patients with chronic-phase CML and for the second-line treatment of imatinib
      resistant or imatinib-intolerant CML.

PMID- 23549841
TI  - Testosterone: a vascular hormone in health and disease.
AB  - Coronary heart disease is a leading cause of premature death in men.
      Epidemiological studies have shown a high prevalence of low serum testosterone
      levels in men with cardiovascular disease (CVD). Furthermore, a low testosterone
      level is associated in some but not in all observational studies with an increase
      in cardiovascular events and mortality. Testosterone has beneficial effects on
      several cardiovascular risk factors, which include cholesterol, endothelial
      dysfunction and inflammation: key mediators of atherosclerosis. A bidirectional
      relationship between low endogenous testosterone levels and concurrent illness
      complicates attempts to validate causality in this association and potential
      mechanistic actions are complex. Testosterone is a vasoactive hormone that
      predominantly has vasodilatory actions on several vascular beds, although some
      studies have reported conflicting effects. In clinical studies, acute and chronic
      testosterone administration increases coronary artery diameter and flow, improves
      cardiac ischaemia and symptoms in men with chronic stable angina and reduces
      peripheral vascular resistance in chronic heart failure. Although the mechanism
      of the action of testosterone on vascular tone in vivo is not understood,
      laboratory research has found that testosterone is an L-calcium channel blocker
      and induces potassium channel activation in vascular smooth muscle cells. Animal
      studies have consistently demonstrated that testosterone is atheroprotective,
      whereas testosterone deficiency promotes the early stages of atherogenesis. The
      translational effects of testosterone between in vitro animal and human studies,
      some of which have conflicting effects, will be discussed in this review. We
      review the evidence for a role of testosterone in vascular health, its
      therapeutic potential and safety in hypogonadal men with CVD, and some of the
      possible underlying mechanisms.

PMID- 23549842
TI  - Modified posterior soft tissue repair for the prevention of early postoperative
      dislocation in total hip arthroplasty.
AB  - PURPOSE: Dislocation following total hip arthroplasty (THA) with the posterior
      approach has been quite a common and bothering complication. Previous researches
      suggest that careful repair of the posterior structures significantly reduces
      this risk. The purposes of the present study were to describe a modified
      posterior soft tissue repair procedure in THA using a suture anchor (TwinFix Ti
      5.0, Smith & Nephew, Andover, MA) and evaluate the early postoperative
      dislocation rate. METHODS: From July 2004 to June 2008, 220 consecutive primary
      total hip arthroplasties were performed using the modified surgical approach. The
      average age in the group was 46.4 years (range from 21 to 90) at the time of the
      procedure. The rate of postoperative hip dislocation, as well as any signs of
      complications related to the technique, has been observed and analyzed in this
      study. RESULTS: There was no postoperative dislocation following primary THA in
      220 cases, and no signs of complications related to the technique, such as
      greater trochanteric fractures and sciatic nerve palsy, have been noted in any of
      the cases at their most recent follow-up. CONCLUSIONS: These initial results
      demonstrate that the modified repair in THA using the suture anchor can serve as
      an effective and reliable mean for prevention of early postoperative dislocation.

PMID- 23549843
TI  - Organic nitrogen components in soils from southeast China.
AB  - OBJECTIVE: To investigate the amounts of extractable organic nitrogen (EON), and
      the relationships between EON and total extractable nitrogen (TEN), especially
      the amino acids (AAs) adsorbed by soils, and a series of other hydrolyzed soil
      nitrogen indices in typical land use soil types from southeast China. Under
      traditional agricultural planting conditions, the functions of EON, especially
      AAs in the rhizosphere and in bulk soil zones were also investigated. METHODS:
      Pot experiments were conducted using plants of pakchoi (Brassica chinensis L.)
      and rice (Oryza sativa L.). In the rhizosphere and bulk soil zone studies,
      organic nitrogen components were extracted with either distilled water, 0.5 mol/L
      K2SO4 or acid hydrolysis. RESULTS: K2SO4-EON constituted more than 30% of TEN
      pools. K2SO4-extractable AAs accounted for 25% of EON pools and nearly 10% of TEN
      pools in rhizosphere soils. Overall, both K2SO4-EON and extractable AAs contents
      had positive correlations with TEN pools. CONCLUSIONS: EON represented a major
      component of TEN pools in garden and paddy soils under traditional planting
      conditions. Although only a small proportion of the EON was present in the form
      of water-extractable and K2SO4-extractable AAs, the release of AAs from soil
      exchangeable sites might be an important source of organic nitrogen (N) for plant
      growth. Our findings suggest that the content of most organic forms of N was
      significantly greater in rhizosphere than in bulk soil zone samples. However, it
      was also apparent that the TEN pool content was lower in rhizosphere than in bulk
      soil samples without added N.

PMID- 23549844
TI  - Effect of physiological harvest stages on the composition of bioactive compounds
      in Cavendish bananas.
AB  - The combined influence of maturation, ripening, and climate on the profile of
      bioactive compounds was studied in banana (Musa acuminata, AAA, Cavendish, cv.
      Grande Naine). Their bioactive compounds were determined by the Folin-Ciocalteu
      assay and high-performance thin layer chromatographic (HPTLC) method. The
      polyphenol content of bananas harvested after 400 degree days remained unchanged
      during ripening, while bananas harvested after 600 and 900 degree days exhibited
      a significant polyphenol increase. Although dopamine was the polyphenol with the
      highest concentration in banana peels during the green developmental stage and
      ripening, its kinetics differed from the total polyphenol profile. Our results
      showed that this matrix of choice (maturation, ripening, and climate) may allow
      selection of the banana (M. acuminata, AAA, Cavendish, cv. Grande Naine) status
      that will produce optimal concentrations of identified compounds with human
      health relevance.

PMID- 23549845
TI  - Determination of the genetic diversity of vegetable soybean [Glycine max (L.)
      Merr.] using EST-SSR markers.
AB  - The development of expressed sequence tag-derived simple sequence repeats (EST
      SSRs) provided a useful tool for investigating plant genetic diversity. In the
      present study, 22 polymorphic EST-SSRs from grain soybean were identified and
      used to assess the genetic diversity in 48 vegetable soybean accessions. Among
      the 22 EST-SSR loci, tri-nucleotides were the most abundant repeats, accounting
      for 50.00% of the total motifs. GAA was the most common motif among tri
      nucleotide repeats, with a frequency of 18.18%. Polymorphic analysis identified a
      total of 71 alleles, with an average of 3.23 per locus. The polymorphism
      information content (PIC) values ranged from 0.144 to 0.630, with a mean of
      0.386. Observed heterozygosity (Ho) values varied from 0.0196 to 1.0000, with an
      average of 0.6092, while the expected heterozygosity (He) values ranged from
      0.1502 to 0.6840, with a mean value of 0.4616. Principal coordinate analysis and
      phylogenetic tree analysis indicated that the accessions could be assigned to
      different groups based to a large extent on their geographic distribution, and
      most accessions from China were clustered into the same groups. These results
      suggest that Chinese vegetable soybean accessions have a narrow genetic base. The
      results of this study indicate that EST-SSRs from grain soybean have high
      transferability to vegetable soybean, and that these new markers would be helpful
      in taxonomy, molecular breeding, and comparative mapping studies of vegetable
      soybean in the future.

PMID- 23549846
TI  - Screening Chinese soybean genotypes for Agrobacterium-mediated genetic
      transformation suitability.
AB  - The Agrobacterium-mediated transformation system is the most commonly used method
      in soybean transformation. Screening of soybean genotypes favorable for
      Agrobacterium-infection and tissue regeneration is the most important step to
      establish an efficient genetic transformation system. In this study, twenty
      soybean genotypes that originated from different soybean production regions in
      China were screened for transient infection, regeneration capacity, and stable
      transgenic efficiency. Three genotypes, Yuechun 04-5, Yuechun 03-3, and Tianlong
      1, showed comparable stable transgenic efficiencies with that of the previously
      reported American genotypes Williams 82 and Jack in our experimental system. For
      the Tianlong 1, the average stable transformation efficiency is 4.59%, higher
      than that of control genotypes (Jack and Williams 82), which is enough for
      further genomic research and genetic engineering. While polymerase chain reaction
      (PCR), LibertyLink strips, and beta-glucuronidase (GUS) staining assays were used
      to detect the insertion and expression of the transgene, leaves painted with 135
      mg/L Basta could efficiently identify the transformants.

PMID- 23549847
TI  - Determination of genetic relationships between evergreen azalea cultivars in
      China using AFLP markers.
AB  - Evergreen azaleas are among the most important ornamental shrubs in China. Today,
      there are probably over 300 cultivars preserved in different nurseries, but with
      little information available on the cultivar itself or relationships between
      cultivars. Amplified fragment length polymorphism (AFLP) markers were employed to
      determine the genetic relationships between evergreen azalea cultivars in China.
      One hundred and thirty genotypes collected from gardens and nurseries, including
      cultivars classified in the groups East, West, Hairy, and Summer, unknown
      cultivars, and close species, were analyzed using three primer pairs. A total of
      408 polymorphic fragments were generated by AFLP reactions with an average of 136
      fragments per primer pair. The average values of expected heterozygosity and
      Shannon's information index were 0.3395 and 0.5153, respectively. Genetic
      similarities were generated based on Dice coefficients, used to construct a
      neighbor joining tree, and bootstrapped for 100 replicates in Treecon V1.3b.
      Principal coordinate analysis (PCO) was performed based on Dice distances using
      NTSYS-pc software. The AFLP technique was useful for analyzing genetic diversity
      in evergreen azaleas. Cluster analysis revealed that cultivars in the West and
      Summer groups were quite distinct from other groups in the four-group
      classification system and that the East and Hairy groups should be redefined.

PMID- 23549848
TI  - Variation in glucosinolates in pak choi cultivars and various organs at different
      stages of vegetative growth during the harvest period.
AB  - Glucosinolates (GSs) play an important role in plant defense systems and human
      nutrition. We investigated the content and composition of GSs in the shoots and
      roots of seven cultivars of pak choi. We found that 'Si Yue Man' had the highest
      total and aliphatic GS contents in the shoots and the highest benzenic GS content
      in the roots, 'Shanghai Qing' contained the highest amounts of benzenic and total
      GS contents in the roots, while 'Nanjing Zhong Gan Bai' had the lowest benzenic,
      indole, and total GS contents in both the shoots and roots. Therefore, the 'Si
      Yue Man' cultivar appears to be a good candidate for future breeding. Variation
      between the shoots and roots was also examined, and a significant correlation
      among the total, aliphatic, and some individual GSs was found, which is of value
      in agricultural breeding. GS concentrations of the leaf, petiole, and root
      increased dramatically during the period of rapid growth of the dry matter of the
      plant 10 to 20 d after transplantation, reaching peak values on Day 20 and
      decreasing on Day 25. We conclude that the pak choi should be harvested and
      consumed from 20 to 25 d after transplantation to take advantages of the high GS
      content in the plant.

PMID- 23549849
TI  - Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide.
AB  - Busulfan/cyclophosphamide (Bu/Cy) conditioning regimen has been widely used to
      treat cancer patients, while their effects on major internal organs in females
      are not fully understood. We treated female mice with Bu/Cy, and examined the
      histopathology of major internal organs on Day 30 after the treatment. The
      results show that Bu/Cy treatment affected the ovaries most extensively, while it
      had less effect on the spleen, lungs, and kidneys, and no effect on the heart,
      liver, stomach, and pancreas. To better understand the effect of Bu/Cy on the
      ovaries, we counted follicles, and determined the levels of ovarian steroids. The
      Bu/Cy-treated mice showed a reduction of primordial and primary follicles
      (P<0.01) on Day 30 and a marked loss of follicles at all developmental stages
      (P<0.01) on Day 60. Plasma levels of estradiol and progesterone in Bu/Cy-treated
      mice decreased by 43.9% and 61.4%, respectively. Thus, there was a gradual
      process of follicle loss and low estradiol in Bu/Cy-treated mice; this is a
      profile similar to what is found in women with premature ovarian failure (POF).
      The Bu/Cy-treated mice may serve as a useful animal model to study the dynamics
      of follicle loss in women undergoing POF.

PMID- 23549850
TI  - Purification and studies on characteristics of cholinesterases from Daphnia
      magna.
AB  - Due to their significant value in both economy and ecology, Daphnia had long been
      employed to investigate in vivo response of cholinesterase (ChE) in
      anticholinesterase exposures, whereas the type constitution and property of the
      enzyme remained unclear. A type of ChE was purified from Daphnia magna using a
      three-step procedure, i.e., Triton X-100 extraction, ammonium sulfate
      precipitation, and diethylaminoethyl (DEAE)-SepharoseTM-Fast-Flow chromatography.
      According to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE), molecular mass of the purified ChE was estimated to be 84 kDa. Based on
      substrate studies, the purified enzyme preferred butyrylthiocholine iodide (BTCh)
      [with maximum velocity (Vmax)/Michaelis constant (Km)=8.428 L/(min.mg protein)]
      to acetylthiocholine iodide (ATCh) [with Vmax/Km=5.346 L/(min.mg protein)] as its
      substrate. Activity of the purified enzyme was suppressed by high concentrations
      of either ATCh or BTCh. Inhibitor studies showed that the purified enzyme was
      more sensitive towards inhibition by tetraisopropylpyrophosphoramide (iso-OMPA)
      than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284C51).
      Result of the study suggested that the purified ChE was more like a type of
      pseudocholinesterase, and it also suggested that Daphnia magna contained multiple
      types of ChE in their bodies.

PMID- 23549851
TI  - Ultrastructure and phylogeny of Ustilago coicis.
AB  - Ustilago coicis causes serious smut on Coix lacryma-jobi in Dayang Town, Jinyun
      County, Zhejiang Province of China. In this paper, ultrastructural assessments on
      fungus-host interactions and teliospore development are presented, and molecular
      phylogenetic analyses have been done to elucidate the phylogenetic placement of
      the taxon. Hyphal growth within infected tissues was both intracellular and
      intercellular and on the surface of fungus-host interaction, and the fungal cell
      wall and the invaginated host plasma membrane were separated by a sheath
      comprising two distinct layers between the fungal cell wall and the invaginated
      host plasma membrane. Ornamentation development of teliospore walls was unique as
      they appeared to be originated from the exosporium. In addition, internal
      transcribed spacer (ITS) and large subunit (LSU) sequence data showed that U.
      coicis is closely related to Ustilago trichophora which infects grass species of
      the genus Echinochloa (Poaceae).

PMID- 23549852
TI  - Enhancing production of a 24-membered ring macrolide compound by a marine
      bacterium using response surface methodology.
AB  - A 24-membered ring macrolide compound, macrolactin A has potential applications
      in pharmaceuticals for its anti-infectious and antiviral activity. In this study,
      macrolactin A was produced by a marine bacterium, which was identified as
      Bacillus subtilis by 16S ribosomal RNA (rRNA) sequence analysis. Electrospray
      ionization mass spectrometry (ESI/MS) and nuclear magnetic resonance (NMR)
      spectroscopy analyses were used to characterize this compound. To improve the
      production, response surface methodology (RSM) involving Box-Behnken design (BBD)
      was employed. Faeces bombycis, the main by-product in sericulture, was used as a
      nitrogen source in fermentation. The interactions between three significant
      factors, F. bombycis, soluble starch, and (NH4)2SO4 were investigated. A
      quadratic model was constructed to fit the production and the factors. Optimum
      medium composition was obtained by analysis of the model. When cultivated in the
      optimum medium, the production of macrolactin A was increased to 851 mg/L, 2.7
      times as compared to the original. This study is also useful to find another way
      in utilizing F. bombycis.

PMID- 23549853
TI  - Be careful! Avoiding duplication: a case study.

PMID- 23549855
TI  - Difficulties in diagnosing severe Pneumocystis jiroveci pneumonia after rituximab
      therapy for steroid-dependent nephrotic syndrome.

PMID- 23549856
TI  - The health-related quality-of-life impact of nocturnal awakenings in the middle
      aged and older Finnish population.
AB  - PURPOSE: The aim of the study is to examine the health-related quality-of-life
      (HRQOL) impact of the nocturnal awakenings and the duration of the sleep in the
      Finnish middle-aged and older population. METHODS: Cross-sectional sample
      consisted of 823 community-dwelling persons aged 55-75 living in a single
      municipality in a rural area of Eastern Finland. Frequency of the nocturnal
      awakenings was dichotomized as reporting "frequent," if the participant reported
      subjectively awakening "often" or "very often," and "infrequent" if the
      participant reported awakening "sometimes" or less frequently. HRQOL was measured
      with a preference-based HRQOL-index instrument, 15D. Analyses were adjusted for
      gender, BMI, morbidities, depression, employment and marital status, current
      smoking and drinking, exercise, recommendation to exercise from a health care
      professional, and subjective opinion about own exercise habits. RESULTS: Frequent
      nocturnal awakenings had statistically and clinically significant negative impact
      on HRQOL, the mean (SE) adjusted marginal HRQOL impact being -0.0416 (0.006).
      More than 10 and less than 6.5 h of daily sleep were associated with higher
      probability of having low HRQOL, adjusted odd ratios (95 % CI) being 2.65 (1.11
      6.33) and 2.65 (1.55-4.52), respectively. However, the changes in daily sleep
      duration did not have noticeable influence on the significance or magnitude of
      the negative HRQOL impact of the frequent nocturnal awakenings. CONCLUSIONS:
      Nocturnal awakenings displayed a strong independent association with decreased
      HRQOL. The findings suggest that both clinicians and researchers should pay
      closer attention to nocturnal awakenings and other sleep problems in order to
      find ways to improve the quality of life in individuals with such conditions.

PMID- 23549857
TI  - Measuring health-related quality of life among adults in Singapore: population
      norms for the EQ-5D.
AB  - PURPOSE: To provide population norms for the Euro-QoL-5D (EQ-5D) according to
      age, sex, ethnicity and language version using a representative sample of adults
      aged 18 years and above in the Singapore population. METHODS: A total of 5,594
      respondents who completed the self-administrated paper-based EQ-5D in the
      Singapore Mental Health Study were included in this study. Socio-demographic
      characteristics were captured using a structured questionnaire. RESULTS: The mean
      age of the sample was 40 years, females comprised 52.2 % of the sample and 78 %
      were of Chinese descent. Pain/discomfort was the most frequently reported problem
      (15.3 %) followed by anxiety/depression (8.2 %), whilst self-care (0.5 %) was the
      least frequently reported problem in the Singapore population. Multiple linear
      regression analysis revealed that younger age, higher income, those employed and
      those administered English version of the questionnaire were significantly
      associated with higher EQ-5D index. CONCLUSIONS: This article provides important
      population norms for the EQ-5D for measuring health-related quality of life
      (HRQOL) both in clinical settings and in the research context. Our results
      suggest that socio-demographic factors should be taken into account when
      assessing HRQOL among adults in Singapore.

PMID- 23549858
TI  - Preoperative platelet count associates with survival and distant metastasis in
      surgically resected colorectal cancer patients.
AB  - OBJECTIVE: Platelets have been implicated in cancer metastasis and prognosis. No
      population-based study has been reported as to whether preoperative platelet
      count directly predicts metastatic recurrence of colorectal cancer (CRC)
      patients. DESIGN: Using a well-characterized cohort of 1,513 surgically resected
      CRC patients, we assessed the predictive roles of preoperative platelet count in
      overall survival, overall recurrence, as well as locoregional and distant
      metastatic recurrences. RESULTS: Patients with clinically high platelet count
      (>=400 * 10(9)/L) measured within 1 month before surgery had a significantly
      unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI]
      1.34-2.05, P = 2.6 * 10(-6), P(log rank) = 1.1 * 10(-11)) and recurrence (HR =
      1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet
      count with recurrence was evident only in patients with metastatic (HR = 2.81,
      1.67-4.74, P = 1.1 * 10(-4), P(log rank) = 2.6 * 10(-6)) but not locoregional
      recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The
      findings were internally validated through bootstrap resampling (P < 0.01 at 98.6
      % of resampling). Consistently, platelet count was significantly higher in
      deceased than living patients (P < 0.0001) and in patients with metastatic
      recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001).
      Time-dependent modeling indicated that the increased risks for death and
      metastasis associated with elevated preoperative platelet counts persisted up to
      5 years after surgery. CONCLUSION: Our data demonstrated that clinically high
      level of preoperative platelets was an independent predictor of CRC survival and
      metastasis. As an important component of the routinely tested complete blood
      count panel, platelet count may be a cost-effective and noninvasive marker for
      CRC prognosis and a potential intervention target to prevent metastatic
      recurrence.

PMID- 23549859
TI  - Colonic intussusception induced by massive tubular adenoma in a patient post
      radiofrequency ablation.

PMID- 23549860
TI  - [Oncological imaging].

PMID- 23549861
TI  - Closed platysmotomy: a new procedure to treat platysma bands.

PMID- 23549863
TI  - [Integrated headache care network. Kiel Migraine and Headache Center and German
      National Headache Treatment Network].
AB  - Migraine and other headaches affect 54 million people in Germany. They rank among
      the ten most severely disabling complaints and the three most expensive
      neurological disorders. Nevertheless, they are not adequately recognized in the
      healthcare system with sketchy diagnoses and inadequate treatment. This
      inadequate care is not primarily due to a lack of medical and scientific
      knowledge on the development and treatment of headaches but is predominantly due
      to organizational deficits in the healthcare system and in the implementation of
      current knowledge. To overcome the organizational barriers the national headache
      treatment network was initiated in Germany. For the first time it allows national
      cross-sectoral and multidisciplinary links between inpatient and outpatient care.
      A hand in hand treatment programme, better education, better information exchange
      between all partners and combined efforts using clearly defined treatment
      pathways and goals are the basis for state of the art and efficient treatment
      results. The treatment network is geared towards the specialized treatment of
      severely affected patients with chronic headache disorders. A national network of
      outpatient and inpatient pain therapists in both practices and hospitals works
      hand in hand to optimally alleviate pain in a comprehensive cross-sectoral and
      multidisciplinary manner. For therapy refractive disorders, a high-intensive
      supraregional fully inpatient treatment can be arranged. This concept offers for
      the first time a nationwide coordinated treatment without limitation by
      specialization and bureaucratic remuneration sectors.

PMID- 23549862
TI  - FGF-23, vascular calcification, and cardiovascular diseases in chronic
      hemodialysis patients.
AB  - INTRODUCTION: Chronic hemodialysis (HD) patients have bad prognosis and
      cardiovascular diseases (CVD) represent their main threatening complication.
      Fibroblast growth factor (FGF-23) has been associated with all kinds of evil
      consequences, including cardiovascular morbidity, but some studies demonstrated
      the contrary. Therefore, it is important to know whether FGF-23 is associated
      with cardiovascular risk or protection. The purpose of this study was to assess
      the links between FGF-23 and intimal vascular calcification (VC) and with the
      presence of CVD in chronic HD patients. PATIENTS AND METHODS: This study was
      carried out on a cohort of randomly selected 88 prevalent HD patients. We
      recorded demographical, clinical, and biochemical data, including FGF-23. VC was
      evaluated on carotid ultrasound. CVD were registered. RESULTS: The mean age was
      59.68 +/- 14.49 years, HD vintage was 59.61 +/- 52.39 months, and 20 patients
      were diabetic (22.72 %). VC was present in 54 patients (61.4 %) and 25 patients
      (28.4 %) had CVD. FGF-23 correlated positively with HD vintage (r = 0.37; p <
      0.001) and iPTH (r = 0.21; p = 0.048). FGF-23 did not correlate with VC score.
      Patients with CVD were older (p = 0.006), had lower FGF-23 (p = 0.008), higher VC
      score (p = 0.009), lower Hb (p = 0.008), albumin (p = 0.003), and creatinine (p =
      0.03). Low FGF-23 was identified as a risk factor for CVD. CONCLUSION: We report
      on a novel association between low FGF23 and CVD in chronic HD patients and a
      lack of correlation of FGF-23 with VC. FGF-23 could play a role in cardiovascular
      protection that remains to be confirmed in larger studies.

PMID- 23549864
TI  - Bioequivalence of saxagliptin/metformin immediate release (IR) fixed-dose
      combination tablets and single-component saxagliptin and metformin IR tablets in
      healthy adult subjects.
AB  - BACKGROUND: As compared with individual tablets, saxagliptin/metformin immediate
      release (IR) fixed-dose combination (FDC) tablets offer the potential for
      increased convenience, compliance, and adherence for patients requiring
      combination therapy. OBJECTIVES: Two bioequivalence studies assessed the fed
      state and the fasted-state bioequivalence of saxagliptin/metformin IR 2.5 mg/500
      mg FDC (study 1) and saxagliptin/metformin IR 2.5 mg/1,000 mg FDC (study 2)
      relative to the same dosage strengths of the individual component tablets
      [saxagliptin (OnglyzaTM) and metformin IR (Glucophage((r)))] administered
      concurrently. STUDY DESIGNS: These were randomized, open-label, single-dose, four
      period, four-treatment, crossover studies in healthy subjects (n = 24 in each
      study). The treatments in study 1 were a saxagliptin/metformin IR 2.5 mg/500 mg
      FDC tablet in the fed and fasted states on separate occasions, and saxagliptin
      2.5 mg and metformin IR 500 mg tablets co-administered in the fed state and
      fasted states on separate occasions. The treatments in study 2 were a
      saxagliptin/metformin IR 2.5 mg/1,000 mg FDC tablet in the fed and fasted states
      on separate occasions, and saxagliptin 2.5 mg and metformin IR 1,000 mg co
      administered in the fed state and fasted states on separate occasions. The
      pharmacokinetics, safety, and tolerability of each treatment were evaluated.
      RESULTS: For both studies, saxagliptin and metformin in the FDCs were
      bioequivalent to the individual components in both the fed and the fasted states
      as the limits of the 90 % confidence interval of the ratio of adjusted geometric
      means for all key pharmacokinetic parameters were contained within the predefined
      0.800 to 1.250 bioequivalence criteria. Co-administration of saxagliptin and
      metformin IR was generally safe and well tolerated as the FDCs or as individual
      tablets. CONCLUSIONS: Saxagliptin/metformin IR 2.5 mg/500 mg and
      saxagliptin/metformin IR 2.5 mg/1,000 mg FDCs were bioequivalent to individual
      tablets of saxagliptin and metformin of the same strengths in both the fed and
      the fasted states. No unexpected safety findings were observed with
      saxagliptin/metformin IR administration. The tolerability of the FDC of
      saxagliptin/metformin IR was comparable to that of the co-administered individual
      components. These results indicate that the safety and efficacy profile of co
      administration of saxagliptin and metformin can be extended to the
      saxagliptin/metformin IR FDC tablets.

PMID- 23549865
TI  - To operate or to radiate: the added value of the maximal standardized uptake
      value in PET-FDG in cervical cancer patients.
AB  - Cervical cancer is one of the leading causes of death among women with
      gynecological malignancies. In early stages of the disease (IB-IIA), surgical
      treatment alone is usually the treatment of choice. However, some high-risk
      patients are referred for postoperative chemo-radiotherapy, leading to increased
      morbidity. Maximal Standardized Uptake Value (SUVmax) is a positron emission
      tomography-computed tomography (PET-CT)-derived semiquantitative measurement of
      fluorodeoxyglucose (FDG) uptake in a defined lesion and may reflect tumor
      aggressiveness. The purpose of this study was to determine whether preoperative
      high SUVmax values can be used for the selection of initial therapy, thus
      reducing the side effects resulting from bimodal treatment. PET-CT studies of 46
      cervical cancer patients who underwent surgery were reviewed, and SUVmax data
      were collected. Statistical analyses were performed to determine the
      relationships between SUVmax values and clinical parameters, modalities of
      treatment, and outcomes. SUVmax was found to correlate with depth of tumor
      invasion (r = 0.46, p < 0.003). A statistically significant correlation was also
      found between SUVmax and histological grade, with the mean and variance of SUVmax
      significantly lower for grade one, as compared to grades two and three (mean
      1.10, 11.06, and 8.88; variance 3.57, 45.60, and 29.79, respectively; p < 0.0001
      and p = 0.076). A possible SUVmax cutoff value of 10.08 was identified as a
      potential indicator of increased risk for receiving bimodal treatment, with a
      sensitivity of 61.5 % and a specificity of 75.8 %. SUVmax can be used for
      differentiating early-stage cervical cancer patients who will need postoperative
      adjuvant treatment and therefore can serve as an additional modality to reduce
      the need for bimodal therapy in these patients.

PMID- 23549866
TI  - Temsirolimus controlled metastatic advanced renal cell carcinoma for over 4
      years: a case study.
AB  - We present a case report of long-term response with temsirolimus in cytokine
      refractory metastatic renal cell carcinoma (RCC). A 74-year-old Japanese man was
      diagnosed with advanced RCC in November 2007 and enrolled in a phase II study to
      examine the safety and efficacy of temsirolimus in East Asian patients with
      metastatic RCC. He achieved a partial response 12 months after starting treatment
      with temsirolimus followed by stable disease for 39 months. The most notable
      toxicity was grade 3 pericardial effusion, which gradually increased 2 years
      after treatment start until discontinuation of the trial resulting in pericardial
      tamponade, grade 3 hypoxia associated with chronic obstructive pulmonary disease
      (COPD), which he had before the trial, and latent interstitial pneumonia. The
      cease of temsirolimus led to improvement of interstitial pneumonia while the
      target lesion progressed. He died of progressive COPD and latent interstitial
      pneumonia 4 months after discontinuing temsirolimus. To our knowledge, he lived
      the longest in East Asian populations since starting temsirolimus.

PMID- 23549868
TI  - Pulse wave velocity 24-hour monitoring with one-site measurements by
      oscillometry.
AB  - This review describes issues for the estimation of pulse wave velocity (PWV)
      under ambulatory conditions using oscillometric systems. The difference between
      the principles of measuring the PWV by the standard method and by oscillometry is
      shown, and information on device validation studies is summarized. It was
      concluded that currently oscillometry is a method that is very convenient to use
      in the 24-hour monitoring of the PWV, is relatively accurate, and is reasonably
      comfortable for the patient. Several indices with the same principles as those in
      the analysis of blood pressure in ambulatory monitoring of blood pressure, namely
      the assessment of load, variability, and circadian rhythm, are proposed.

PMID- 23549867
TI  - HCN1 channels as targets for anesthetic and nonanesthetic propofol analogs in the
      amelioration of mechanical and thermal hyperalgesia in a mouse model of
      neuropathic pain.
AB  - Chronic pain after peripheral nerve injury is associated with afferent
      hyperexcitability and upregulation of hyperpolarization-activated, cyclic
      nucleotide-regulated (HCN)-mediated IH pacemaker currents in sensory neurons. HCN
      channels thus constitute an attractive target for treating chronic pain. HCN
      channels are ubiquitously expressed; analgesics targeting HCN1-rich cells in the
      peripheral nervous system must spare the cardiac pacemaker current (carried
      mostly by HCN2 and HCN4) and the central nervous system (where all four isoforms
      are expressed). The alkylphenol general anesthetic propofol (2,6-di-iso
      propylphenol) selectively inhibits HCN1 channels versus HCN2-HCN4 and exhibits a
      modest pharmacokinetic preference for the periphery. Consequently, we
      hypothesized that propofol, and congeners, should be antihyperalgesic. Alkyl
      substituted propofol analogs have different rank-order potencies with respect to
      HCN1 inhibition, GABA(A) receptor (GABA(A)-R) potentiation, and general
      anesthesia. Thus, 2,6- and 2,4-di-tertbutylphenol (2,6- and 2,4-DTBP,
      respectively) are more potent HCN1 antagonists than propofol, whereas 2,6- and
      2,4-di-sec-butylphenol (2,6- and 2,4-DSBP, respectively) are less potent. In
      contrast, DSBPs, but not DTBPs, enhance GABA(A)-R function and are general
      anesthetics. 2,6-DTBP retained propofol's selectivity for HCN1 over HCN2-HCN4. In
      a peripheral nerve ligation model of neuropathic pain, 2,6-DTBP and subhypnotic
      propofol are antihyperalgesic. The findings are consistent with these
      alkylphenols exerting analgesia via non-GABA(A)-R targets and suggest that
      antagonism of central HCN1 channels may be of limited importance to general
      anesthesia. Alkylphenols are hydrophobic, and thus potential modifiers of lipid
      bilayers, but their effects on HCN channels are due to direct drug-channel
      interactions because they have little bilayer-modifying effect at therapeutic
      concentrations. The alkylphenol antihyperalgesic target may be HCN1 channels in
      the damaged peripheral nervous system.

PMID- 23549869
TI  - Dual targeting of the type 1 insulin-like growth factor receptor and its ligands
      as an effective antiangiogenic strategy.
AB  - BACKGROUND: In pediatric tumor xenograft models, tumor-derived insulin growth
      factor (IGF-2) results in intrinsic resistance to IGF-IR-targeted antibodies,
      maintaining continued tumor angiogenesis. We evaluated the antiangiogenic
      activity of a ligand-binding antibody (MEDI-573) alone or in combination with IGF
      I receptor binding antibodies (MAB391, CP01-B02). METHODS: IGF-stimulated
      signaling was monitored by increased Akt phosphorylation in sarcoma and human
      umbilical cord vascular endothelial cells (HUVEC). Angiogenesis was determined in
      vitro using capillary tube formation in HUVECs and in vivo using a VEGF
      stimulated Matrigel assay. Tumor growth delay was examined in 4 sarcoma xenograft
      models. RESULTS: The IGF ligand-binding antibody MEDI-573 suppressed Akt
      phosphorylation induced by exogenous IGF-I and IGF-2 in sarcoma cells. Receptor
      binding antibodies suppressed IGF-I stimulation of Akt phosphorylation, but IGF-2
      circumvented this effect and maintained HUVEC tube formation. MEDI-573 inhibited
      HUVEC proliferation and tube formation in vitro, but did not inhibit angiogenesis
      in vivo, probably because MEDI-573 binds murine IGF-I with low affinity. However,
      in vitro antiangiogenic activity of MEDI-573 was also circumvented by human
      recombinant IGF-I. The combination of receptor- and ligand-binding antibodies
      completely suppressed VEGF-stimulated proliferation of HUVECs in the presence of
      IGF-I and IGF-2, prevented ligand-induced phosphorylation of IGF-IR/IR receptors,
      and suppressed VEGF/IGF-2-driven angiogenesis in vivo. The combination of CP1-BO2
      plus MEDI-573 was significantly superior to therapy with either antibody alone
      against IGF-I and IGF-2 secreting pediatric sarcoma xenograft models.
      CONCLUSIONS: These results suggest that combination of antibodies targeting IGF
      receptor and ligands may be an effective therapeutic strategy to block
      angiogenesis for IGF-driven tumors.

PMID- 23549870
TI  - Altered DNA methylation landscapes of polycomb-repressed loci are associated with
      prostate cancer progression and ERG oncogene expression in prostate cancer.
AB  - PURPOSE: To assess differentially methylated "landscapes" according to prostate
      cancer Gleason score (GS) and ERG oncogene expression status, and to determine
      the extent of polycomb group (PcG) target gene involvement, we sought to assess
      the genome-wide DNA methylation profile of prostate cancer according to Gleason
      score and ERG expression. EXPERIMENTAL DESIGN: Genomic DNA from 39 prostate
      cancer specimens was hybridized to CpG island microarrays through differential
      methylation hybridization. We compared methylation profiles between Gleason score
      and ERG expression status as well as Gleason score stratified by ERG expression
      status. In addition, we compared results from our dataset to publicly available
      datasets of histone modifications in benign prostate cells. RESULTS: We
      discovered hundreds of distinct differentially methylated regions (DMR)
      associated with increasing Gleason score and ERG. Furthermore, the number of DMRs
      associated with Gleason score was greatly expanded by stratifying samples into
      ERG-positive versus ERG-negative, with ERG-positive/GS-associated DMRs being
      primarily hypermethylated as opposed to hypomethylated. Finally, we found that
      there was a significant overlap between either Gleason score-related or ERG
      hypermethylated DMRs and distinct regions in benign epithelial cells that have
      PcG signatures (H3K27me3, SUZ12) and lack active gene expression signatures
      (H3K4me3, RNA pol II). CONCLUSIONS: This work defines methylation landscapes of
      prostate cancer according to Gleason score, and suggests that initiating genetic
      events may influence the prostate cancer epigenome, which is further perturbed as
      prostate cancer progresses. Moreover, CpG islands with silent chromatin
      signatures in benign cells are particularly susceptible to prostate cancer
      related hypermethylation.

PMID- 23549871
TI  - Prespecified candidate biomarkers identify follicular lymphoma patients who
      achieved longer progression-free survival with bortezomib-rituximab versus
      rituximab.
AB  - PURPOSE: Identify subgroups of patients with relapsed/refractory follicular
      lymphoma deriving substantial progression-free survival (PFS) benefit with
      bortezomib-rituximab versus rituximab in the phase III LYM-3001 study.
      EXPERIMENTAL DESIGN: A total of 676 patients were randomized to five 5-week
      cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this
      prespecified analysis of candidate protein biomarkers and genes was an
      exploratory objective. Archived tumor tissue and whole blood samples were
      collected at baseline. Immunohistochemistry and genetic analyses were completed
      for 4 proteins and 8 genes. RESULTS: In initial pairwise analyses, using
      individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1
      P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS
      benefit with bortezomib-rituximab versus rituximab, controlling for multiple
      comparison corrections. The pair was analyzed under dominant, recessive, and
      additive genetic models, with significant association with PFS seen under the
      dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G
      allele, low CD68 expression (<=50 CD68-positive cells), population frequency:
      43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months
      with rituximab (HR 0.47, P < 0.0001), and there was a significant overall
      survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to
      next antilymphoma therapy was longer in the bortezomib-rituximab group. In
      biomarker-negative patients, no significant efficacy differences were seen
      between treatment groups. Similar proportions of patients had high-risk features
      in the biomarker-positive and biomarker-negative subsets. CONCLUSIONS: Patients
      with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly
      longer PFS and greater clinical benefit with bortezomib-rituximab versus
      rituximab.

PMID- 23549872
TI  - ASS1 as a novel tumor suppressor gene in myxofibrosarcomas: aberrant loss via
      epigenetic DNA methylation confers aggressive phenotypes, negative prognostic
      impact, and therapeutic relevance.
AB  - PURPOSE: The principal goals were to identify and validate targetable metabolic
      drivers relevant to myxofibrosarcoma pathogenesis using a published
      transcriptome. EXPERIMENTAL DESIGN: As the most significantly downregulated gene
      regulating amino acid metabolism, argininosuccinate synthetase (ASS1) was
      selected for further analysis by methylation-specific PCR, pyrosequencing, and
      immunohistochemistry of myxofibrosarcoma samples. The roles of ASS1 in
      tumorigenesis and the therapeutic relevance of the arginine-depriving agent
      pegylated arginine deiminase (ADI-PEG20) were elucidated in ASS1-deficient
      myxofibrosarcoma cell lines and xenografts with and without stable ASS1
      reexpression. RESULTS: ASS1 promoter hypermethylation was detected in
      myxofibrosarcoma samples and cell lines and was strongly linked to ASS1 protein
      deficiency. The latter correlated with increased tumor grade and stage and
      independently predicted a worse survival. ASS1-deficient cell lines were
      auxotrophic for arginine and susceptible to ADI-PEG20 treatment, with dose
      dependent reductions in cell viability and tumor growth attributable to cell
      cycle arrest in the S-phase. ASS1 expression was restored in 2 of 3 ASS1
      deficient myxofibrosarcoma cell lines by 5-aza-2'-deoxycytidine, abrogating the
      inhibitory effect of ADI-PEG20. Conditioned media following ASS1 reexpression
      attenuated HUVEC tube-forming capability, which was associated with suppression
      of MMP-9 and an antiangiogenic effect in corresponding myxofibrosarcoma
      xenografts. In addition to delayed wound closure and fewer invading cells in a
      Matrigel assay, ASS1 reexpression reduced tumor cell proliferation, induced G1
      phase arrest, and downregulated cyclin E with corresponding growth inhibition in
      soft agar and xenograft assays. CONCLUSIONS: Our findings highlight ASS1 as a
      novel tumor suppressor in myxofibrosarcomas, with loss of expression linked to
      promoter methylation, clinical aggressiveness, and sensitivity to ADI-PEG20.

PMID- 23549873
TI  - Identification of prognosis-relevant subgroups in patients with chemoresistant
      triple-negative breast cancer.
AB  - PURPOSE: Patients with triple-negative breast cancer (TNBC) and residual disease
      after neoadjuvant chemotherapy generally have worse outcome; however, some
      patients with residual tumor after neoadjuvant chemotherapy do not relapse. We
      hypothesize that there are subgroups of patients with chemoresistant TNBC with
      different prognosis. EXPERIMENTAL DESIGN: Forty-nine chemoresistant cases from
      111 patients with TNBC treated with neoadjuvant chemotherapy (M.D. Anderson
      Cancer Center, Houston, TX) constituted the discovery cohort, and 25
      chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The
      Methodist Hospital, Houston, TX) were chosen for validation. Extended validation
      was carried out in 269 operable TNBC predicted to be chemoresistant by expression
      pattern from published datasets. RESULTS: We established a seven-gene prognostic
      signature using dChip and gene set enrichment analyses. In the independent
      validation cohort, the classifier predicted correctly with positive predictive
      value of 75.0% and negative predictive value (i.e., relapse-free survival; RFS)
      of 76.9% at 3 years. Those predicted to relapse had a HR of 4.67 [95% confidence
      interval (CI): 1.27-17.15] for relapse in 3 years. In extended validation,
      patients predicted not to relapse exhibited 3-year RFS of 78.9%, whereas the 3
      year RFS was 48.5% for patients predicted to relapse, with HR of 2.61 (95% CI:
      1.52-4.49). The TNBC subgroup that predicted to have relatively favorable
      prognosis was characterized by high expression of "luminal-like" genes [androgen
      receptor (AR) and GATA3], whereas the subgroup with worse prognosis was
      characterized by expression of cancer stem-cell markers. CONCLUSION: We developed
      a clinically relevant signature for patients with chemoresistant TNBC. For these
      women, new therapeutic strategies like targeting AR activation or cancer stem
      cells may need to be developed.

PMID- 23549874
TI  - Molecular pathways: the complex roles of inflammation pathways in the development
      and treatment of liver cancer.
AB  - Inflammatory signals from the surrounding microenvironment play important roles
      in tumor promotion. Key inflammatory mediators and pathways that induce and
      sustain tumorigenesis have recently been identified in many different cancers.
      Hepatocellular carcinoma is a paradigm for inflammation-induced cancer, as it
      most frequently develops in the setting of chronic hepatitis, consecutive
      cellular damage, and compensatory regeneration. Recent studies revealed that
      liver damage-mediated inflammation and carcinogenesis are triggered by a complex
      cross-talk between NF-kappaB, c-jun-NH2-kinase, and STAT3 signaling pathways.
      Molecular dissection of the mechanisms involved in the interplay between these
      pathways identified promising new targets for therapeutic intervention. Targeting
      different components of the signaling cascades may provide efficient means for
      blocking the apparently irreversible sequence of events initiated by chronic
      liver inflammation and culminating in liver cancer.

PMID- 23549875
TI  - Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of
      BRAF(V600E) colorectal cancer.
AB  - PURPOSE: BRAF(V600E) mutations are associated with poor clinical prognosis in
      colorectal cancer (CRC). Although selective BRAF inhibitors are effective for
      treatment of melanoma, comparable efforts in CRC have been disappointing. Here,
      we investigated potential mechanisms underlying this resistance to BRAF
      inhibitors in BRAF(V600E) CRC. EXPERIMENTAL DESIGN: We examined phosphoinositide
      3-kinase (PI3K)/mTOR signaling in BRAF(V600E) CRC cell lines after BRAF
      inhibition and cell viability and apoptosis after combined BRAF and PI3K/mTOR
      inhibition. We assessed the efficacy of in vivo combination treatment using a
      novel genetically engineered mouse model (GEMM) for BRAF(V600E) CRC. RESULTS:
      Western blot analysis revealed sustained PI3K/mTOR signaling upon BRAF
      inhibition. Our BRAF(V600E) GEMM presented with sessile serrated adenomas/polyps,
      as seen in humans. Combination treatment in vivo resulted in induction of
      apoptosis and tumor regression. CONCLUSIONS: We have established a novel GEMM to
      interrogate BRAF(V600E) CRC biology and identify more efficacious treatment
      strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored
      in clinical trials.

PMID- 23549877
TI  - Oncolytic virotherapy needs trials, not access programs.
AB  - Oncolytic virotherapy is a novel treatment for cancer that exerts direct lytic
      and indirect immune-mediated antitumor effects. A Finnish research team has
      reported on an advanced therapy access program for oncolytic adenovirus. The
      strengths and weaknesses of this approach are highlighted with a view to
      informing future study conduct.

PMID- 23549876
TI  - Predictive biomarkers for bevacizumab: are we there yet?
AB  - Therapy targeting VEGF has become the standard of care in several solid
      malignancies. Early investigations attempting to identify predictive markers for
      the efficacy of therapy failed to identify any predictive markers that could help
      oncologists decide who should-and, more importantly, who should not-receive VEGF
      targeted therapies. However, interest has been renewed in predictive biomarkers
      for VEGF-targeted therapies, especially in light of the fact that the U.S. Food
      and Drug Administration withdrew approval for use of bevacizumab, an antibody to
      VEGF, in patients with metastatic breast cancer. In a recent publication in the
      Journal of Clinical Oncology, investigators identified circulating VEGF and tumor
      neuropilin-1 expression as potential predictive biomarkers for bevacizumab. From
      this perspective, we provide a critical evaluation of the use of these markers
      and the need for validation in prospective clinical trials.

PMID- 23549878
TI  - Molecular pathways: environmental estrogens activate nongenomic signaling to
      developmentally reprogram the epigenome.
AB  - Exposure to environmental xenoestrogens is a major health concern because of the
      ability of these compounds to perturb estrogen receptor (ER) signaling and act as
      endocrine disrupting compounds (EDC). Inappropriate exposure to EDCs during
      development, even at low doses, can predispose individuals to an increased
      lifetime risk of disease, including cancer. Recent data indicate that perinatal
      exposure to EDCs increases cancer risk by (re)programming the epigenome via
      alterations in DNA and histone methylation. We and others have begun to dissect
      the mechanisms by which xenoestrogens disrupt the epigenetic machinery to
      reprogram the epigenome and induce developmental reprogramming. Our studies
      revealed that xenoestrogens induce nongenomic ER signaling to activate PI3K/AKT,
      resulting in AKT phosphorylation and inactivation of the histone
      methyltransferase EZH2, thus providing a direct link to disruption of the
      epigenome. Other epigenetic "readers, writers, and erasers" may also be targeted
      by nongenomic signaling, suggesting this is a central mechanism by which
      xenoestrogens and other EDCs disrupt the epigenome to induce developmental
      reprogramming. Elucidating mechanisms of developmental reprogramming of the
      epigenome is important for understanding how environmental exposures increase
      cancer risk, and provides a rationale for developing epigenetic interventions
      that can reverse the effects of environmental exposures to reduce cancer risk.

PMID- 23549879
TI  - Sequential inhibitor therapy in CML: in vitro simulation elucidates the pattern
      of resistance mutations after second- and third-line treatment.
AB  - PURPOSE: Dasatinib and nilotinib are active in imatinib-resistant chronic
      myelocytic leukemia (CML) and many patients undergo sequential treatment. We
      aimed at modeling sequential tyrosine kinase inhibitor (TKI) resistance in vitro
      to compare the sequences imatinib-nilotinib-dasatinib and imatinib-dasatinib
      nilotinib. EXPERIMENTAL DESIGN: We designed an in vitro model for sequential TKI
      resistance in CML. Replicates of imatinib-resistant cell lines were treated with
      dasatinib or nilotinib. Second-line resistant replicates were exposed to third
      line treatment. RESULTS: Growth of all replicates in all three lines of treatment
      was associated with T315I. However, T315I occurred with low abundance and did not
      increase during sequential treatment. Nilotinib second-line more often gave rise
      to sequential resistance compared with dasatinib due to pre-existing P-loop
      mutations, especially at suboptimal drug concentration. In contrast, mutations
      predisposing to dasatinib resistance such as F317C/V and V299L did not occur
      before dasatinib exposure. Nilotinib third-line did not overcome imatinib
      dasatinib resistance due to pre-existing T315I or P-loop/V299L or P-loop/F317
      exchanges. Dasatinib third-line suppressed imatinib-nilotinib-resistant
      replicates with residual sensitivity. CONCLUSIONS: Sequential acquisition of BCR
      ABL drug resistance mutations in CML might be underestimated. Resistance to
      sequential TKI monotherapy in vitro more often was associated with stepwise
      acquisition of drug-specific compound mutations compared with T315I. Pre-existing
      mutations strongly limited the activity of both third-line treatments, and the
      activity of nilotinib second-line in vitro critically depended on drug
      concentration.

PMID- 23549880
TI  - Myeloid differentiation factor 88 promotes growth and metastasis of human
      hepatocellular carcinoma.
AB  - PURPOSE: To investigate the expression of myeloid differentiation factor 88
      (MyD88) in hepatocellular carcinoma (HCC) and its prognostic value in patients
      with HCC. EXPERIMENTAL DESIGN: Expression of MyD88 was detected by
      immunohistochemistry in surgical HCC specimens (n = 110). The correlation of
      MyD88 expression to clinicopathologic characteristics was analyzed. The
      involvement of MyD88 in tumor growth and invasion was investigated. RESULTS: The
      expression of MyD88 was significantly higher in HCC tumors than that in adjacent
      nontumor tissues. Particularly, high expression of MyD88 was found in HCCs with
      late tumor stage (P = 0.029). Patients with high MyD88 staining revealed a higher
      recurrence rate (65% vs. 40%; P = 0.008). Kaplan-Meier analysis showed that
      recurrence-free survival (RFS; P = 0.011) and overall survival (OS; P = 0.022)
      were significantly worse among patients with high MyD88 staining. Univariate and
      multivariate analyses revealed that MyD88 was an independent predictor for OS and
      RFS. Ectopic expression of MyD88 promoted HCC cell proliferation and invasion in
      vitro. Suppression of MyD88 expression with lentivirus encoding short hairpin RNA
      reduced tumor growth and invasion, as well as lung metastasis. Finally, silencing
      of MyD88 inhibited the activation of NF-kappaB and AKT in HCC cells, whereas
      forced expression of MyD88 was able to enhance the activation of NF-kappaB and
      p38/extracellular signal-regulated kinase without Toll-like receptor/interleukin
      1 receptor (TLR/IL-1R) signaling. CONCLUSION: Elevated expression of MyD88 may
      promote tumor growth and metastasis via both TLR/IL-1R-dependent and -independent
      signaling and may serve as a biomarker for prognosis of patients with HCC.

PMID- 23549881
TI  - Applying combined optical tweezers and fluorescence microscopy technologies to
      manipulate cell adhesions for cell-to-cell interaction study.
AB  - Cell-to-cell interactions are important for the regulation of various cell
      activities, such as proliferation, differentiation, and apoptosis. This paper
      presents an approach to studying cell-to-cell interactions at a single-cell level
      through manipulating cell adhesions with optical tweezers. Experiments are
      performed on leukemia cancer cells and stromal cells to demonstrate the
      feasibility of this method. After the adhesion properties of leukemia cells on
      stromal cells are characterized, fluorescence intensity is used as a label to
      study the Wnt signaling pathway of leukemia cells. The activities of the Wnt
      signaling pathway of K562 cells on M210B4 and HS5 cells are examined based on
      fluorescence analysis. The reliability of the fluorescence imaging is confirmed
      through comparison with traditional flow cytometry analysis. The proposed
      approach will offer new avenues to investigate otherwise inaccessible mechanisms
      in cell-to-cell interactions. 

PMID- 23549882
TI  - Survival after recurrent esophageal carcinoma has not improved over the past 18
      years.
AB  - BACKGROUND: Numerous patients will develop recurrent disease after esophagectomy
      for esophageal carcinoma (EC). In literature, survival after recurrent EC is poor
      with 6-8 months. In these studies, diagnostic imaging during follow-up (FU) is
      routinely performed. In the Netherlands, routine imaging is not part of FU and
      only performed on indication. The aim of this study was to determine survival
      after diagnosis of recurrent disease in patients after esophagectomy without
      routine imaging during FU. METHODS: All EC patients who underwent esophagectomy
      between 1993 and 2010 were included and followed for clinical evidence of
      recurrent EC. Location, symptoms, diagnosis, and treatment of recurrent disease
      were registered. Pattern of recurrence was compared between patients who
      underwent neoadjuvant therapy and patients who underwent surgery alone. Survival
      after detection of recurrence was determined in all patients and related to the
      year of surgery. RESULTS: A total of 493 of 1,088 patients (45 %) who underwent
      esophagectomy between 1993 and 2010 developed recurrent disease. Median interval
      between esophagectomy and recurrence was 10.5 months. Within the first 2 years
      after surgery, 33 % of patients developed recurrent EC. The majority of patients
      (51 %) were diagnosed with distant metastases. Locoregional recurrence occurred
      significantly less often among patients who underwent neoadjuvant therapy (6 vs
      16 %, p = .017). Median survival after diagnosis of recurrent disease was 3
      months. No relation was observed between the year of surgery and survival after
      recurrent disease (p = .931). CONCLUSIONS: Survival after recurrent EC in
      patients who undergo FU without routine imaging after esophagectomy is
      approximately 3 months and has not improved over the past 18 years.

PMID- 23549883
TI  - Phase II trial of neoadjuvant docetaxel and cisplatin followed by intensity
      modulated radiotherapy with concurrent cisplatin in locally advanced
      nasopharyngeal carcinoma.
AB  - PURPOSE: To evaluate the feasibility and efficacy of neoadjuvant chemotherapy
      involving docetaxel and cisplatin followed by intensity-modulated radiotherapy
      (IMRT) with concurrent cisplatin in patients with newly diagnosed stage III to
      IVB nasopharyngeal carcinoma (NPC). METHODS: Docetaxel (75 mg/m(2) on day 1) and
      cisplatin (75 mg/m(2) on day 1) were administered on a 3-week cycle for 2
      courses, followed by radical IMRT (72 Gy/33F/6.5-7 W) with concurrent cisplatin
      (75 mg/m(2), on day 1) every 3 weeks for 2 cycles. RESULTS: From June 2008 to
      October 2010, forty-six patients were recruited in this trial. Forty-five
      patients completed neoadjuvant setting, and all patients completed planned
      concurrent chemoradiotherapy (CCRT). The complete and partial response rates were
      28.3 and 56.5 % after neoadjuvant chemotherapy, and 91.3, 8.7 % after CCRT,
      respectively. After median follow-up of 26 months (range 12-39 months), one
      patient experienced local recurrence and 4 patients developed distant metastasis.
      The 3-year overall survival and progression-free survival rate were 94.1 and 72.7
      %, respectively. Neutropenia (37.0 %) and vomiting (28.3 %) were the most common
      Grade 3-4 adverse effects during neoadjuvant course, while mucositis (30.4 %),
      xerostomia (30.4 %) and radiodermatitis (21.7 %) were the most common Grades 3
      acute toxicities during CCRT. Xerostomia (73.9 %), dysphagia (56.5 %), hear loss
      (30.4 %) and skin reaction (21.7 %) were the common Grade 1-2 late effects. There
      were no Grades 3-4 late toxicities. CONCLUSIONS: The protocol of neoadjuvant
      docetaxel and cisplatin followed by IMRT with concurrent cisplatin was well
      tolerated, with outstanding compliance and efficacy in locally advanced NPC,
      which deserved further follow-up.

PMID- 23549884
TI  - HN gene C-terminal extension of Newcastle disease virus is not the determinant of
      the enteric tropism.
AB  - The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV)
      plays an important role in virus pathogenicity and tissue tropism. Sequence
      analysis revealed that the HN gene of many asymptomatic enteric NDV strains
      encodes a larger open reading frame (616 amino acids, aa) with additional 39 aa
      at its C-terminus when compared with that (577 aa) of respirotropic NDV strains.
      Therefore, it has been suspected that the HN C-terminal extension may contribute
      to the enteric tropism. In the present study, we generated a NDV respirotropic
      strain LaSota-based recombinant virus with a HN C-terminal extension of 39 aa
      derived from an enterotropic NDV strain using reverse genetics technology. The
      biological characterization of the recombinant virus, rLS-HN-ex, showed that the
      HN C-terminal extension slightly attenuated the virus pathogenicity in
      embryonated eggs and in day-old chicks when compared to the parental LaSota
      virus. However, the HN C-terminal extension did not alter virus tissue tropism.
      In infected chickens, the recombinant virus was detected and re-isolated from the
      tracheal tissue, but not from the intestinal tissue, exhibiting a similar
      respirotropic tissue preference as its parental LaSota strain. These results
      demonstrated that the HN protein C-terminal extension of NDV is not the
      determinant of the virus enteric tropism. 

PMID- 23549886
TI  - Attributed relational graphs for cell nucleus segmentation in fluorescence
      microscopy images.
AB  - More rapid and accurate high-throughput screening in molecular cellular biology
      research has become possible with the development of automated microscopy
      imaging, for which cell nucleus segmentation commonly constitutes the core step.
      Although several promising methods exist for segmenting the nuclei of monolayer
      isolated and less-confluent cells, it still remains an open problem to segment
      the nuclei of more-confluent cells, which tend to grow in overlayers. To address
      this problem, we propose a new model-based nucleus segmentation algorithm. This
      algorithm models how a human locates a nucleus by identifying the nucleus
      boundaries and piecing them together. In this algorithm, we define four types of
      primitives to represent nucleus boundaries at different orientations and
      construct an attributed relational graph on the primitives to represent their
      spatial relations. Then, we reduce the nucleus identification problem to finding
      predefined structural patterns in the constructed graph and also use the
      primitives in region growing to delineate the nucleus borders. Working with
      fluorescence microscopy images, our experiments demonstrate that the proposed
      algorithm identifies nuclei better than previous nucleus segmentation algorithms.

PMID- 23549887
TI  - Coherent plane wave compounding for very high frame rate ultrasonography of
      rapidly moving targets.
AB  - Coherent plane wave compounding is a promising technique for achieving very high
      frame rate imaging without compromising image quality or penetration. However,
      this approach relies on the hypothesis that the imaged object is not moving
      during the compounded scan sequence, which is not the case in cardiovascular
      imaging. This work investigates the effect of tissue motion on retrospective
      transmit focusing in coherent compounded plane wave imaging (PWI). Two compound
      scan sequences were studied based on a linear and alternating sequence of tilted
      plane waves, with different timing characteristics. Simulation studies revealed
      potentially severe degradations in the retrospective focusing process, where both
      radial and lateral resolution was reduced, lateral shifts of the imaged medium
      were introduced, and losses in signal-to-noise ratio (SNR) were inferred. For
      myocardial imaging, physiological tissue displacements were on the order of half
      a wavelength, leading to SNR losses up to 35 dB, and reductions of contrast by 40
      dB. No significant difference was observed between the different tilt sequences.
      A motion compensation technique based on cross-correlation was introduced, which
      significantly recovered the losses in SNR and contrast for physiological tissue
      velocities. Worst case losses in SNR and contrast were recovered by 35 dB and 27
      35 dB, respectively. The effects of motion were demonstrated in vivo when imaging
      a rat heart. Using PWI, very high frame rates up to 463 fps were achieved at high
      image quality, but a motion correction scheme was then required. 

PMID- 23549885
TI  - Targeting sirtuin-1 in Huntington's disease: rationale and current status.
AB  - Huntington's disease (HD) is an autosomal dominant hereditary disease caused by a
      trinucleotide repeat mutation in the huntingtin gene that results in an increased
      number of glutamine residues in the N terminus of huntingtin protein. Mutant
      huntingtin leads to progressive impairment of motor function, cognitive
      dysfunction, and neuropsychiatric disturbance. There are no disease-modifying
      treatments available. During the past decade, sirtuin-1 (SIRT1) has been the
      focus of intense investigation and discussion because it regulates longevity in
      multiple organisms and has shown beneficial effects in a variety of models of
      neurodegenerative disorders. Studies in different animal models provide
      convincing evidence that SIRT1 protects neurons in mouse models of HD as well as
      in Caenorhabditis elegans, although controversial results were reported in a fly
      model. Indeed, many connections exist between the deacetylation function of SIRT1
      and its role in neuroprotection. As a result, pharmacological interventions
      targeting SIRT1 might become promising strategies to combat HD. This review
      summarizes recent progress in SIRT1 research, with a focus on the specificity of
      this protein as a potential therapeutic target for HD, as well as existing
      challenges for developing SIRT1 modulators for clinical use.

PMID- 23549888
TI  - A dictionary learning approach for Poisson image deblurring.
AB  - The restoration of images corrupted by blur and Poisson noise is a key issue in
      medical and biological image processing. While most existing methods are based on
      variational models, generally derived from a maximum a posteriori (MAP)
      formulation, recently sparse representations of images have shown to be efficient
      approaches for image recovery. Following this idea, we propose in this paper a
      model containing three terms: a patch-based sparse representation prior over a
      learned dictionary, the pixel-based total variation regularization term and a
      data-fidelity term capturing the statistics of Poisson noise. The resulting
      optimization problem can be solved by an alternating minimization technique
      combined with variable splitting. Extensive experimental results suggest that in
      terms of visual quality, peak signal-to-noise ratio value and the method noise,
      the proposed algorithm outperforms state-of-the-art methods. 

PMID- 23549889
TI  - Image inpainting on the basis of spectral structure from 2-D nonharmonic
      analysis.
AB  - The restoration of images by digital inpainting is an active field of research
      and such algorithms are, in fact, now widely used. Conventional methods generally
      apply textures that are most similar to the areas around the missing region or
      use a large image database. However, this produces discontinuous textures and
      thus unsatisfactory results. Here, we propose a new technique to overcome this
      limitation by using signal prediction based on the nonharmonic analysis (NHA)
      technique proposed by the authors. NHA can be used to extract accurate spectra,
      irrespective of the window function, and its frequency resolution is less than
      that of the discrete Fourier transform. The proposed method sequentially
      generates new textures on the basis of the spectrum obtained by NHA. Missing
      regions from the spectrum are repaired using an improved cost function for 2D
      NHA. The proposed method is evaluated using the standard images Lena, Barbara,
      Airplane, Pepper, and Mandrill. The results show an improvement in MSE of about
      10-20 compared with the examplar-based method and good subjective quality.

PMID- 23549890
TI  - Orientation imaging microscopy with optimized convergence angle using CBED
      patterns in TEMs.
AB  - Grain size statistics, texture, and grain boundary distribution are
      microstructural characteristics that greatly influence materials properties.
      These characteristics can be derived from an orientation map obtained using
      orientation imaging microscopy (OIM) techniques. The OIM techniques are generally
      performed using a transmission electron microscopy (TEM) for nanomaterials.
      Although some of these techniques have limited applicability in certain
      situations, others have limited availability because of external hardware
      required. In this paper, an automated method to generate orientation maps using
      convergence beam electron diffraction patterns obtained in a conventional TEM
      setup is presented. This method is based upon dynamical diffraction theory that
      describes electron diffraction more accurately as compared with kinematical
      theory used by several existing OIM techniques. In addition, the method of this
      paper uses wide angle convergent beam electron diffraction for performing OIM. It
      is shown in this paper that the use of the wide angle convergent electron beam
      provides additional information that is not available otherwise. Together, the
      presented method exploits the additional information and combines it with the
      calculations from the dynamical theory to provide accurate orientation maps in a
      conventional TEM setup. The automated method of this paper is applied to a
      platinum thin film sample. The presented method correctly identified the texture
      preference in the sample.

PMID- 23549891
TI  - Grassmannian regularized structured multi-view embedding for image
      classification.
AB  - Images are usually represented by features from multiple views, e.g., color and
      texture. In image classification, the goal is to fuse all the multi-view features
      in a reasonable manner and achieve satisfactory classification performance.
      However, the features are often different in nature and it is nontrivial to fuse
      them. Particularly, some extracted features are redundant or noisy and are
      consequently not discriminative for classification. To alleviate these problems
      in an image classification context, we propose in this paper a novel multi-view
      embedding framework, termed as Grassmannian regularized structured multi-view
      embedding, or GrassReg for short. GrassReg transfers the graph Laplacian obtained
      from each view to a point on the Grassmann manifold and penalizes the
      disagreement between different views according to Grassmannian distance.
      Therefore, a view that is consistent with others is more important than a view
      that disagrees with others for learning a unified subspace for multi-view data
      representation. In addition, we impose the group sparsity penalty onto the low
      dimensional embeddings obtained hence they can better explore the group structure
      of the intrinsic data distribution. Empirically, we compare GrassReg with
      representative multi-view algorithms and show the effectiveness of GrassReg on a
      number of multi-view image data sets.

PMID- 23549892
TI  - Efficient minimum error bounded particle resampling L1 tracker with occlusion
      detection.
AB  - Recently, sparse representation has been applied to visual tracking to find the
      target with the minimum reconstruction error from a target template subspace.
      Though effective, these L1 trackers require high computational costs due to
      numerous calculations for l1 minimization. In addition, the inherent occlusion
      insensitivity of the l1 minimization has not been fully characterized. In this
      paper, we propose an efficient L1 tracker, named bounded particle resampling
      (BPR)-L1 tracker, with a minimum error bound and occlusion detection. First, the
      minimum error bound is calculated from a linear least squares equation and serves
      as a guide for particle resampling in a particle filter (PF) framework. Most of
      the insignificant samples are removed before solving the computationally
      expensive l1 minimization in a two-step testing. The first step, named tau
      testing, compares the sample observation likelihood to an ordered set of
      thresholds to remove insignificant samples without loss of resampling precision.
      The second step, named max testing, identifies the largest sample probability
      relative to the target to further remove insignificant samples without altering
      the tracking result of the current frame. Though sacrificing minimal precision
      during resampling, max testing achieves significant speed up on top of tau
      testing. The BPR-L1 technique can also be beneficial to other trackers that have
      minimum error bounds in a PF framework, especially for trackers based on sparse
      representations. After the error-bound calculation, BPR-L1 performs occlusion
      detection by investigating the trivial coefficients in the l1 minimization. These
      coefficients, by design, contain rich information about image corruptions,
      including occlusion. Detected occlusions are then used to enhance the template
      updating. For evaluation, we conduct experiments on three video applications:
      biometrics (head movement, hand holding object, singers on stage), pedestrians
      (urban travel, hallway monitoring), and cars in traffic (wide area motion
      imagery, ground-mounted perspectives). The proposed BPR-L1 method demonstrates an
      excellent performance as compared with nine state-of-the-art trackers on eleven
      challenging benchmark sequences.

PMID- 23549893
TI  - Multiview Hessian regularization for image annotation.
AB  - The rapid development of computer hardware and Internet technology makes large
      scale data dependent models computationally tractable, and opens a bright avenue
      for annotating images through innovative machine learning algorithms.
      Semisupervised learning (SSL) therefore received intensive attention in recent
      years and was successfully deployed in image annotation. One representative work
      in SSL is Laplacian regularization (LR), which smoothes the conditional
      distribution for classification along the manifold encoded in the graph
      Laplacian, however, it is observed that LR biases the classification function
      toward a constant function that possibly results in poor generalization. In
      addition, LR is developed to handle uniformly distributed data (or single-view
      data), although instances or objects, such as images and videos, are usually
      represented by multiview features, such as color, shape, and texture. In this
      paper, we present multiview Hessian regularization (mHR) to address the above two
      problems in LR-based image annotation. In particular, mHR optimally combines
      multiple HR, each of which is obtained from a particular view of instances, and
      steers the classification function that varies linearly along the data manifold.
      We apply mHR to kernel least squares and support vector machines as two examples
      for image annotation. Extensive experiments on the PASCAL VOC'07 dataset validate
      the effectiveness of mHR by comparing it with baseline algorithms, including LR
      and HR.

PMID- 23549894
TI  - Multiple-kernel, multiple-instance similarity features for efficient visual
      object detection.
AB  - We propose to use the similarity between the sample instance and a number of
      exemplars as features in visual object detection. Concepts from multiple-kernel
      learning and multiple-instance learning are incorporated into our scheme at the
      feature level by properly calculating the similarity. The similarity between two
      instances can be measured by various metrics and by using the information from
      various sources, which mimics the use of multiple kernels for kernel machines.
      Pooling of the similarity values from multiple instances of an object part is
      introduced to cope with alignment inaccuracy between object instances. To deal
      with the high dimensionality of the multiple-kernel multiple-instance similarity
      feature, we propose a forward feature-selection technique and a coarse-to-fine
      learning scheme to find a set of good exemplars, hence we can produce an
      efficient classifier while maintaining a good performance. Both the feature and
      the learning technique have interesting properties. We demonstrate the
      performance of our method using both synthetic data and real-world visual object
      detection data sets.

PMID- 23549895
TI  - GPU accelerated edge-region based level set evolution constrained by 2D gray
      scale histogram.
AB  - Due to its intrinsic nature which allows to easily handle complex shapes and
      topological changes, the level set method (LSM) has been widely used in image
      segmentation. Nevertheless, LSM is computationally expensive, which limits its
      applications in real-time systems. For this purpose, we propose a new level set
      algorithm, which uses simultaneously edge, region, and 2D histogram information
      in order to efficiently segment objects of interest in a given scene. The
      computational complexity of the proposed LSM is greatly reduced by using the
      highly parallelizable lattice Boltzmann method (LBM) with a body force to solve
      the level set equation (LSE). The body force is the link with image data and is
      defined from the proposed LSE. The proposed LSM is then implemented using an
      NVIDIA graphics processing units to fully take advantage of the LBM local nature.
      The new algorithm is effective, robust against noise, independent to the initial
      contour, fast, and highly parallelizable. The edge and region information enable
      to detect objects with and without edges, and the 2D histogram information enable
      the effectiveness of the method in a noisy environment. Experimental results on
      synthetic and real images demonstrate subjectively and objectively the
      performance of the proposed method.

PMID- 23549896
TI  - Sparse stochastic processes and discretization of linear inverse problems.
AB  - We present a novel statistically-based discretization paradigm and derive a class
      of maximum a posteriori (MAP) estimators for solving ill-conditioned linear
      inverse problems. We are guided by the theory of sparse stochastic processes,
      which specifies continuous-domain signals as solutions of linear stochastic
      differential equations. Accordingly, we show that the class of admissible priors
      for the discretized version of the signal is confined to the family of infinitely
      divisible distributions. Our estimators not only cover the well-studied methods
      of Tikhonov and l1-type regularizations as particular cases, but also open the
      door to a broader class of sparsity-promoting regularization schemes that are
      typically nonconvex. We provide an algorithm that handles the corresponding
      nonconvex problems and illustrate the use of our formalism by applying it to
      deconvolution, magnetic resonance imaging, and X-ray tomographic reconstruction
      problems. Finally, we compare the performance of estimators associated with
      models of increasing sparsity.

PMID- 23549897
TI  - Effect of age and exercise on the viscoelastic properties of rat tail tendon.
AB  - Tendon mechanical properties are thought to degrade during aging but improve with
      exercise. A remaining question is whether exercise in aged animals provides
      sufficient regenerative, systemic stimulus to restore younger mechanical
      behaviors. Herein we address that question with tail tendons from aged and
      exercised rats, which would be subject to systemic effects but not direct loading
      from the exercise regimen. Twenty-four month old rats underwent one of three
      treadmill exercise training protocols for 12 months: sedentary (walking at 0
      degrees  incline for 5 min/day), moderate (running at 0 degrees  incline for 30
      min/day), or high (running at 4 degrees  incline for 30 min/day). A group of 9
      month old rats were used to provide an adult control, while a group of 3 month
      old rats provided a young control. Tendons were harvested at sacrifice and
      mechanically tested. Results show significant age-dependent differences in
      modulus, ultimate stress, relaxation rate, and percent relaxation. Relaxation
      rate was strain-dependent, consistent with nonlinear superposition or Schapery
      models but not with quasilinear viscoelasticity (QLV). Trends in exercise data
      suggest that with exercise, tendons assume the elastic character of younger rats
      (lower elastic modulus and ultimate stress).

PMID- 23549898
TI  - Biomechanical phenotyping of central arteries in health and disease: advantages
      of and methods for murine models.
AB  - The stiffness and structural integrity of the arterial wall depends primarily on
      the organization of the extracellular matrix and the cells that fashion and
      maintain this matrix. Fundamental to the latter is a delicate balance in the
      continuous production and removal of structural constituents and the mechanical
      state in which such turnover occurs. Perturbations in this balance due to genetic
      mutations, altered hemodynamics, or pathological processes result in diverse
      vascular phenotypes, many of which have yet to be well characterized
      biomechanically. In this paper, we emphasize the particular need to understand
      regional variations in the biaxial biomechanical properties of central arteries
      in health and disease and, in addition, the need for standardization in the
      associated biaxial testing and quantification. As an example of possible
      experimental methods, we summarize testing protocols that have evolved in our
      laboratory over the past 8 years. Moreover, we note advantages of a four fiber
      family stress-stretch relation for quantifying passive biaxial behaviors, the use
      of stored energy as a convenient scalar metric of the associated material
      stiffness, and the utility of appropriate linearizations of the nonlinear,
      anisotropic relations both for purposes of comparison across laboratories and to
      inform computational fluid-solid-interaction models. We conclude that,
      notwithstanding prior advances, there remain many opportunities to advance our
      understanding of arterial mechanics and mechanobiology, particularly via the
      diverse genetic, pharmacological, and surgical models that are, or soon will be,
      available in the mouse.

PMID- 23549900
TI  - Superparamagnetic iron oxide is suitable to label tendon stem cells and track
      them in vivo with MR imaging.
AB  - Tendon stem cells (TSCs) may be used to effectively repair or regenerate injured
      tendons. However, the fates of TSCs once implanted in vivo remain unclear. This
      study was aimed to determine the feasibility of labeling TSCs with super
      paramagnetic iron oxide (SPIO) nano-particles to track TSCs in vivo using MRI.
      Rabbit TSCs were labeled by incubation with 50 MUg/mL SPIO. Labeling efficiency,
      cell viability, and proliferation were then measured, and the stemness of TSCs
      was tested by quantitative real time RT-PCR (qRT-PCR) and immunocytochemistry. We
      found that the labeling efficiency of TSCs reached as high as 98%, and that
      labeling at 50 MUg/mL SPIO concentrations did not alter cell viability and cell
      proliferation compared to non-labeled control cells. Moreover, the expression
      levels of stem cell markers (Nucleostemin, Nanog, and Oct-4) did not change in
      SPIO-labeled TSCs compared to non-labeled cells. Both labeled and non-labeled
      cells also exhibited similar differentiation potential. Finally, labeled TSCs
      could be detected by MRI both in vitro and in vivo. Taken together, the findings
      of this study show that labeling TSCs with SPIO particles is a feasible approach
      to track TSCs in vivo by MRI, which offers a non-invasive method to monitor
      repair of injured tendons. 

PMID- 23549901
TI  - Mutation breeding of acetoin high producing Bacillus subtilis blocked in 2,3
      butanediol dehydrogenase.
AB  - Bacillus subtilis mutants were obtained after the wild strain JNA 3-10 was
      mutagenized by UV irradiation coupled with diethyl sulfate. A visual filter assay
      was employed for the qualitative identification of 2,3-butanediol dehydrogenase
      (BDH) blocked B. subtilis. Selected mutants were tested for the activities of
      acetoin reductase (AR) and BDH. According to further batch fermentation, one
      mutant named JNA-UD-6 that produced 24.3 % more acetoin than JNA 3-10 with the
      corresponding byproducts of 2,3-butanediol decreased by 39.8 % was isolated. A
      nonsense mutation (p.Tyr118X) that precluded the synthesis of a full-length
      functional AR/BDH within the bdhA gene of JNA-UD-6 was detected. Acetoin
      production of JNA-UD-6 was further improved to about 53.9 g/L in a 5-L fermentor
      with 150 g/L glucose consumed. However,a small amount of 2,3-butanediol was found
      in late phase of JNA-UD-6 fermentation, and it was due to the existence of a
      putative gene that encoding a minor AR. This work proved a strategy to
      efficiently breeding an acetoin high producing strain by traditional mutation
      methods. 

PMID- 23549899
TI  - Physical factors effecting cerebral aneurysm pathophysiology.
AB  - Many factors that are either blood-, wall-, or hemodynamics-borne have been
      associated with the initiation, growth, and rupture of intracranial aneurysms.
      The distribution of cerebral aneurysms around the bifurcations of the circle of
      Willis has provided the impetus for numerous studies trying to link hemodynamic
      factors (flow impingement, pressure, and/or wall shear stress) to aneurysm
      pathophysiology. The focus of this review is to provide a broad overview of such
      hemodynamic associations as well as the subsumed aspects of vascular anatomy and
      wall structure. Hemodynamic factors seem to be correlated to the distribution of
      aneurysms on the intracranial arterial tree and complex, slow flow patterns seem
      to be associated with aneurysm growth and rupture. However, both the prevalence
      of aneurysms in the general population and the incidence of ruptures in the
      aneurysm population are extremely low. This suggests that hemodynamic factors and
      purely mechanical explanations by themselves may serve as necessary, but never as
      necessary and sufficient conditions of this disease's causation. The ultimate
      cause is not yet known, but it is likely an additive or multiplicative effect of
      a handful of biochemical and biomechanical factors.

PMID- 23549902
TI  - Analysis of yeast-like symbiote diversity in the brown planthopper (BPH),
      Nilaparvata lugens Stal, using a novel nested PCR-DGGE protocol.
AB  - Yeast-like symbiotes (YLS) are endosymbionts that are intimately associated with
      the growth, development, reproduction of their host, the brown planthopper,
      Nilaparvata lugens (Hemiptera: Delphacidae). However, it is unclear how many
      species of YLS are found within N. lugens, and how they are related to each
      other. Traditional methods or simple amplification based on 18S rDNA sequence
      does not reliably identify new species quickly and efficiently. Therefore, a
      novel nested PCR-denaturing gradient gel electrophoresis (DGGE) strategy was
      developed in this article to analyze the YLS of brown planthopper using a nested
      PCR protocol that involved the 18S rDNA gene and the 5.8S-ITS gene using fungal
      universal primers. The nested PCR protocol was developed as follows: firstly, the
      18S rDNA gene, and 5.8S-ITS gene were amplified using fungal universal primers.
      Subsequently, these products were used as a template in a second PCR with primers
      ITS1GC-ITS2, ITS1FGC-ITS2, and NFGC-NR, which was suitable for DGGE. Using this
      highly specific molecular approach, we found several previously detected fungi:
      Noda, Pichia guilliermondii, Candida sp., and some previously undetected fungi,
      such as Saccharomycetales sp., Debaryomyces hansenii, and some uncultured fungi.
      In conclusion, the nested PCR system developed in this study, coupled with DGGE
      fingerprinting, offers a new tool for uncovering fungal endosymbiont diversity
      within planthoppers. 

PMID- 23549903
TI  - The intercropping partner affects arbuscular mycorrhizal fungi and Fusarium
      oxysporum f. sp. lycopersici interactions in tomato.
AB  - Arbuscular mycorrhizal fungi (AMF) and their bioprotective aspects are of great
      interest in the context of sustainable agriculture. Combining the benefits of AMF
      with the utilisation of plant species diversity shows great promise for the
      management of plant diseases in environmentally compatible agriculture. In the
      present study, AMF were tested against Fusarium oxysporum f. sp. lycopersici with
      tomato intercropped with either leek, cucumber, basil, fennel or tomato itself.
      Arbuscular mycorrhizal (AM) root colonisation of tomato was clearly affected by
      its intercropping partners. Tomato intercropped with leek showed even a 20 %
      higher AM colonisation rate than tomato intercropped with tomato. Positive
      effects of AMF expressed as an increase of tomato biomass compared to the
      untreated control treatment could be observed in root as well as in shoot
      weights. A compensation of negative effects of F. oxysporum f. sp. lycopersici on
      tomato biomass by AMF was observed in the tomato/leek combination. The
      intercropping partners leek, cucumber, basil and tomato had no effect on F.
      oxysporum f. sp. lycopersici disease incidence or disease severity indicating no
      allelopathic suppression; however, tomato co-cultivated with tomato clearly
      showed a negative effect on one plant/pot with regard to biomass and disease
      severity of F. oxysporum f. sp. lycopersici. Nonetheless, bioprotective effects
      of AMF resulting in the decrease of F. oxysporum f. sp. lycopersici disease
      severity were evident in treatments with AMF and F. oxysporum f. sp. lycopersici
      co-inoculation. However, these bioprotective effects depended on the
      intercropping partner since these effects were only observed in the tomato/leek
      and tomato/basil combination and for the better developed plant of tomato/tomato.
      In conclusion, the effects of the intercropping partner on AMF colonisation of
      tomato are of great interest for crop plant communities and for the influences on
      each other. The outcome of the bioprotective effects of AMF resulting in the
      decrease on F. oxysporum f. sp. lycopersici disease severity and/or compensation
      of plant biomass does not depend on the degree of AM colonisation but more on the
      intercropping partner. 

PMID- 23549904
TI  - The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series
      and Formulation of a Model of Pathogenesis.
AB  - BACKGROUND: Lactic acidosis is an adverse event associated with metformin usage.
      Patients with metformin-associated lactic acidosis (MALA), however, often have
      other conditions contributing to the event. The relative contribution of
      metformin is often unclear. MALA is usually diagnosed without measuring the
      plasma concentrations of metformin. OBJECTIVES: The objectives of this study
      were, first, to examine the plasma concentrations of metformin, lactate and
      creatinine and the arterial pH of patients with suspected MALA and, second, to
      review critically the mechanisms of MALA. METHODS: Patients who were suspected of
      having MALA were identified during the period October 2008-September 2011.
      Repeated blood samples were collected to determine the plasma concentrations of
      lactate, metformin and creatinine. The pH of arterial blood was also measured on
      several occasions in each patient. RESULTS: Patients (n = 15; 9 female, 6 male)
      were 70 +/- 12 years of age. There was one acute metformin overdose (estimated
      dose 5 g). Metformin was undetectable in one patient and one patient had
      therapeutic concentrations of metformin on admission (<5 mg/L). There were ten
      patients with chronic kidney disease, whereby the estimated glomerular filtration
      rate (eGFR) was less than 60 mL/min/1.73 m(2) before the acidotic event.
      Metformin doses ranged from 1 to 3 g daily (excluding the deliberate overdose).
      On admission, the mean plasma concentration of metformin on admission was 29.8 +/
      19.1 mg/L (mean +/- SD), the mean lactate concentration was 12.9 +/- 6.1 mmol/L
      and the mean pH was 7 +/- 0.2. The mean creatinine concentration on admission was
      481 +/- 225 MUmol/L. The main pre-admission symptoms were vomiting and diarrhoea
      (n = 12). There were linear relationships between venous lactate, venous
      creatinine and arterial pH, with the venous plasma concentrations of metformin in
      most patients. Three patients died but metformin was unlikely to have been a
      significant factor. DISCUSSION AND REVIEW: Most patients with MALA presented to
      the hospital with high metformin concentrations. The following factors appear to
      have been involved in the development of MALA in these patients: vomiting and
      diarrhoea, acute kidney injury, high doses or excessive accumulation of
      metformin, and acute disease states leading to tissue hypoxia. The extent of
      metformin accumulation in patients with MALA can be determined by investigating
      the concentrations of metformin. We suggest that the development of MALA is due
      to a positive feedback system involving one or more of these factors. While
      nausea is a common adverse effect of metformin, vomiting and diarrhoea out of the
      ordinary is a clear first sign of MALA. In this condition, dosage with metformin
      should be stopped and patients should receive urgent medical attention.

PMID- 23549905
TI  - Recruitment of Older Adult Patient-Caregiver Dyads for an Online Caregiver
      Resource Program: Lessons Learned.
AB  - Hip fracture is a significant health problem for older adults and generally
      requires surgery followed by intensive rehabilitation. Informal caregivers (CGs)
      can provide vital assistance to older adults recovering from hip fracture.
      Caregiving is a dyadic process that affects both CGs and care recipients (CRs).
      In a feasibility study, we assessed the effects of using a theory-based online
      hip fracture resource program for CGs on both CGs and CRs. In this article, we
      discuss our recruitment process and the lessons learned. Participants were
      recruited from six acute hospitals, and CGs used the online resource program for
      8 weeks. A total of 256 hip fracture patients were screened, and 164 CRs were
      ineligible. CG screening was initiated when CRs were determined to be eligible.
      Among 41 eligible dyads, 36 dyads were recruited. Several challenges to the
      recruitment of these dyads for online studies were identified, including a low
      number of eligible dyads in certain hospitals and difficulty recruiting both the
      CR and the CG during the short hospital stay. Field nurses often had to make
      multiple trips to the hospital to meet with both the CR and the CG. Thus, when a
      subject unit is a dyad recruited from acute settings, the resources required for
      the recruitment may be more than doubled. These challenges could be successfully
      alleviated with careful planning, competent field staff members, collaboration
      with hospital staff members, and efficient field operations.

PMID- 23549906
TI  - Saccharomonospora oceani sp. nov. isolated from marine sediments in Little
      Andaman, India.
AB  - Two actinomycete strains, designated YIM M11168(T) and YIM M11177, were isolated
      from marine sediment samples from Little Andaman, Indian Ocean, and their
      taxonomic position was determined by a polyphasic approach. The two Gram
      positive, aerobic strains were observed to produce branched substrate mycelium
      and aerial hyphae but did not fragment, and no diffusible pigment was produced on
      the media tested. At maturity, spores were formed singly or in pairs on aerial
      hyphae and substrate mycelium, and occasionally the single ones were borne on
      long sporophores. The optimum growth was determined to occur at 28  degrees C, 0
      4 % (w/v) NaCl and pH 7.0-8.0. Whole-cell hydrolysates of both strains contained
      meso-diaminopimelic acid and the diagnostic sugars were determined to be
      galactose, glucose and arabinose. Their predominant menaquinone was found to be
      MK-9(H4). The polar lipids detected in the two strains were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol mannoside,
      phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylethanolamine
      and two unknown phosphoglycolipids. The major fatty acids (>10 %) identified were
      iso-C16:0, iso-C16:1 H, iso-C16:0, C17:1 omega6c for strain YIM M11168(T), iso
      C16:0 and Summed Feature 3 for strain YIM M11177. The G + C contents of the
      genomic DNAs of both strains were determined to be 71.4 %. DNA-DNA hybridization
      relatedness values (78.4 +/- 3.7 %) of these two isolates supported the
      conclusion that they belong to the same species. Based on phylogenetic analysis,
      phenotypic and genotypic data, it is concluded that the two isolates belong to a
      novel species of the genus Saccharomonospora of the family Pseudonocardiaceae.
      The name Saccharomonospora oceani sp. nov. (Type strain YIM M11168(T) = DSM
      45700(T) = JCM 18128(T)) is proposed for the novel species.

PMID- 23549907
TI  - Surgical treatment for osteoporotic vertebral collapse with neurological
      deficits: retrospective comparative study of three procedures--anterior surgery
      versus posterior spinal shorting osteotomy versus posterior spinal fusion using
      vertebroplasty.
AB  - PURPOSE: In general, osteoporotic vertebral collapse (OVC) with neurological
      deficits requires sufficient decompression of neural tissues to restore function
      level in activities of daily living (ADL). However, it remains unclear as to
      which procedure provides better neurological recovery. The primary purpose of
      this study was to compare neurological recovery among three typical procedures
      for OVC with neurological deficits. Secondary purpose was to compare
      postoperative ADL function. METHODS: We retrospectively reviewed data for 88
      patients (29 men and 59 women) with OVC and neurological deficits who underwent
      surgery. Three typical kinds of surgical procedures with different decompression
      methods were used: (1) anterior direct neural decompression and reconstruction
      (AR group: 27 patients), (2) posterior spinal shorting osteotomy with direct
      neural decompression (PS group: 36 patients), and (3) posterior indirect neural
      decompression and short-segment spinal fusion combined with vertebroplasty (VP
      group: 25 patients). We examined clinical results regarding neurological deficits
      and function level in ADL and radiological results. RESULTS: The mean improvement
      rates for neurological deficits and ADL function level were 60.1 and 55.0%,
      respectively. There were no significant differences among three groups in
      improvement rates for neurological deficits or ADL function level. The VP group
      had a significantly lower estimated mean blood loss (338 mL) and mean duration of
      surgery (229 min) than both the AR and PS groups (p < 0.001). CONCLUSION: Direct
      neural decompression is not always necessary, and the majority of patients can be
      treated with a less-invasive procedure such as short-segment posterior spinal
      fusion with indirect decompression combined with vertebroplasty. The high
      priority issue is careful evaluation of patients' general health and osteoporosis
      severity, so that the surgeon can choose the procedure best suited for each
      patient.

PMID- 23549908
TI  - Validation of the Simplified Chinese version of the Core Outcome Measures Index
      (COMI).
AB  - PURPOSE: To translate the Core Outcome Measures Index (COMI) into Simplified
      Chinese and then validate it for Mainland Chinese patients with low back pain
      (LBP). METHODS: A total of 120 consecutive patients with LBP >3 months who
      visited our outpatient clinic from December 2011 to March 2012 were asked to
      complete a questionnaire booklet including the following: (1) the Roland Morris
      disability questionnaire (RMQ) (Fan et al. in Spine 37(10):875-880, 2012), (2)
      the Short Form Health Survey (SF-36) (Zhang et al. in Int J Med Sci 9(7):521-526,
      2012), (3) the Oswestry Disability Index (ODI) (Liu et al. in Spine 34(11):1211
      1216, 2009), (4) visual analogue scale (VAS) measure of pain, and (5) COMI. These
      patients were also asked to complete a second COMI questionnaire and a transition
      questionnaire (5-point Likert scale: better, a little better, no change, a little
      worse, worse) and to return the second COMI questionnaire via mail within 1
      month. RESULTS: The floor effects for the COMI items ranged from 5.8 to 12.5 %.
      High values (28.3, 27.5, and 25.8 %, respectively) were found for symptom
      specific quality of life, social disability, and work disability. Regarding the
      ceiling effects, the social and work disabilities were relatively high at 17.5
      and 24.2 %, respectively. For other items, the values ranged from 0 to 14.2 %.
      Neither floor nor ceiling effects were found for the COMI summary score.
      Excellent correlations were found between the COMI pain scores and VAS scores
      (Rho = 0.89) and between the COMI pain and the SF-36 bodily pain domain (Rho =
      0.84). Other individual items and summary scores showed a very good correlation
      (Rho = 0.54-0.72) with the corresponding questionnaires except for "symptom
      specific well-being" (0.31-0.45). One-way repeated measures ANOVA was used to
      determine the intraclass correlation coefficient (ICC). The ICC for the entire
      COMI score was 0.91 (95 % CI 0.85-0.94) and 0.81-0.86 for the two pain scores
      (back and leg). The "minimum detectable change'' (MDC 95 %) for the COMI summary
      score was 1.91 points. No significant difference in the mean values was found for
      the repeated scores of individual items or the summary score. CONCLUSION: The
      Simplified Chinese version of COMI showed satisfactory reliability and good
      psychometric properties. This concise questionnaire is suitable for widespread
      use in Mainland China.

PMID- 23549910
TI  - The retreat of the less fit allele in a population-controlled model for
      population genetics.
AB  - It is shown that the solutions of a single-locus diploid model with population
      control for the spatial and temporal interaction of the three genotypes approach
      a constant-density equilibrium in which only the more fit allele is present,
      provided the density dependent birth rate and fitnesses have certain properties.
      The speed at which this phenomenon spreads is at least as great as that of the
      linearization of the corresponding Fisher equation. A larger upper bound for this
      speed is also obtained. 

PMID- 23549911
TI  - Innovation adoption: a review of theories and constructs.
AB  - Many theoretical frameworks seek to describe the dynamic process of the
      implementation of innovations. Little is known, however, about factors related to
      decisions to adopt innovations and how the likelihood of adoption of innovations
      can be increased. Using a narrative synthesis approach, this paper compared
      constructs theorized to be related to adoption of innovations proposed in
      existing theoretical frameworks in order to identify characteristics likely to
      increase adoption of innovations. The overall goal was to identify elements
      across adoption frameworks that are potentially modifiable and, thus, might be
      employed to improve the adoption of evidence-based practices. The review
      identified 20 theoretical frameworks that could be grouped into two broad
      categories: theories that mainly address the adoption process (N = 10) and
      theories that address adoption within the context of implementation, diffusion,
      dissemination, and/or sustainability (N = 10). Constructs of leadership,
      operational size and structure, innovation fit with norms and values, and
      attitudes/motivation toward innovations each are mentioned in at least half of
      the theories, though there were no consistent definitions of measures for these
      constructs. A lack of precise definitions and measurement of constructs suggests
      further work is needed to increase our understanding of adoption of innovations.

PMID- 23549909
TI  - Combined olmesartan, amlodipine, and hydrochlorothiazide therapy in randomized
      patients with hypertension: a subgroup analysis of the TRINITY study by age.
AB  - BACKGROUND: Hypertension is often inadequately controlled in older people.
      OBJECTIVE: This prespecified subgroup analysis assessed the efficacy and safety
      of an olmesartan medoxomil (OM) 40 mg/amlodipine besylate (AML) 10
      mg/hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with
      the 3 components as dual-combination treatments in participants with hypertension
      who were <65 and >= 65 years of age. Within the >= 65 years of age subgroup,
      efficacy and safety were also summarized for participants >= 75 years of age.
      STUDY DESIGN: 12-week, multicenter, double-blind, randomized, parallel-group
      study. SETTING: 317 ambulatory care sites in the US and Puerto Rico.
      PARTICIPANTS: Individuals >= 18 years of age with mean seated blood pressure
      (SeBP) >= 140/100 or >= 160/90 mmHg off antihypertensive medication on 2
      consecutive clinic visits with no recent history of significant cerebrovascular
      disease, coronary artery disease, heart failure (New York Heart Association class
      III or IV), severe renal insufficiency, or uncontrolled diabetes (HbA1c >9 %).
      INTERVENTION: Participants were randomized, stratified by age, diabetes status,
      and race to one of four treatment assignments: OM 40/AML 10/HCTZ 25 mg, OM 40/AML
      10 mg, OM 40/HCTZ 25 mg, or AML 10/HCTZ 25 mg. MAIN OUTCOME MEASURE: Least
      squares (LS) mean change from baseline in seated diastolic blood pressure (SeDBP)
      at week 12 (last observation carried forward) in each age subgroup (prespecified
      analysis). RESULTS: Of the 2492 randomized participants in the study (total
      cohort), 2021 (81.1 %) were <65 and 471 (18.9 %) were >= 65 years of age,
      including 79 (3.2 %) who were >= 75 years of age. OM 40/AML 10/HCTZ 25 mg triple
      combination treatment resulted in a significantly greater reduction in LS mean
      SeDBP at week 12 than dual-combination component treatments in participants in
      both cohorts: <65 years (21.0 vs. 14.2-17.2 mmHg; p < 0.0001) and >= 65 years
      (23.7 vs. 17.3-20.0 mmHg; p <= 0.002). Similarly, triple-combination treatment
      resulted in a greater reduction in LS mean seated systolic blood pressure (SeSBP)
      at week 12 than dual-combination component treatments: <65 years (38.2 vs. 28.3
      31.4 mmHg; p < 0.0001) and >= 65 years (39.2 vs. 29.3-31.1 mmHg; p < 0.0001).
      Triple-combination treatment was more effective than dual-combination treatments
      in enabling participants to reach SeBP goal (<140/90 mmHg [<130/80 mmHg in
      participants with diabetes, chronic kidney disease, or chronic cardiovascular
      disease]) in both age subgroups (<65 years: 65 vs. 34-50 %, respectively, p <
      0.0001 and >= 65 years: 63 vs. 32-39 %; p <= 0.0004). All 4 treatments were safe
      and well tolerated with low discontinuation rates in both age subgroups. There
      were no clinically relevant differences in the incidence of treatment-emergent
      adverse events between participants <65 and >= 65 years of age receiving triple
      combination treatment. CONCLUSION: Triple-combination treatment with OM 40/AML
      10/HCTZ 25 mg was well tolerated and more effective in lowering BP than the
      component dual-combination treatments in elderly and non-elderly subgroups.

PMID- 23549912
TI  - Physico-chemical stability of busulfan in injectable solutions in various
      administration packages.
AB  - BACKGROUND AND OBJECTIVES: Busulfan is used as part of a conditioning regimen
      prior to hematopoietic stem cell transplantation for the treatment of certain
      cancers and immune deficiency syndromes. Due to its instability in aqueous
      preparations, busulfan for infusion is prepared from a concentrate and has a
      relatively short shelf life once prepared. The purpose of this study was to
      identify the most suitable storage container and temperature to maximize the
      shelf life of busulfan therapeutic infusions prepared from Busilvex((r)).
      METHODS: Busilvex((r)) 6 mg/mL was diluted to 0.55 mg/mL with 0.9 % NaCl and
      aliquots dispensed into polypropylene syringes, polyvinyl chloride bags, and
      glass bottles. Three storage temperatures were evaluated: 2-8  degrees C, 13-15 
      degrees C (thermostatically controlled chamber), and room temperature (20 +/- 5 
      degrees C). At set time points, samples were analysed for busulfan content, using
      a high-performance liquid chromatography (HPLC) system with ultraviolet
      detection. The change in pH and osmolarity on storage was also determined, and
      solutions were inspected visually for formation of a precipitate or colour
      change. To determine the contribution of precipitation to loss of busulfan
      content on storage, samples from one time series were treated with the solvent
      dimethylacetamide prior to HPLC separation and quantitation of busulfan. RESULTS:
      The results of the active substance content monitoring study over a 48-h period
      demonstrate that busulfan solution is stable at a 5 % threshold, at 2-8  degrees
      C for 16 h in syringes, 14 h in glass bottles, and 6 h in bags. In addition, the
      period of stability decreases as the temperature increases (4 h at 20 +/- 5 
      degrees C). The solution is considered to be stable, subject to precipitation
      liable to be observed regardless of the temperature. CONCLUSION: The best
      stability was observed for busulfan solutions placed at 2-8  degrees C in
      syringes. This study demonstrated that precipitation, in addition to hydrolysis,
      has a significant influence on the busulfan content.

PMID- 23549913
TI  - Steroid injections in the treatment of humeral unicameral bone cysts: long-term
      follow-up and review of the literature.
AB  - BACKGROUND: Retrospective evaluation of long-term effectiveness of the steroid
      injections treatment in patients with unicameral bone cysts (UBC). METHODS: From
      January 1993 to April 2005, 23 children affected by proximal humeral UBC were
      evaluated according to the Neer-Cole classification system and treated with
      serial methylprednisolone acetate's injections. The patients were followed up at
      1, 3, 6 and 12 months and then every year until the adolescence. RESULTS: After
      treatment, in 15 out of 23 patients (65.2%), the humeral cysts were referred,
      respectively, as Grade 1 and in four as Grade 2. In 4 patients, a refracture
      occurred. Statistical analysis showed an overall good response in 82.6% of
      patients at the end of the follow-up. Minor complication including skin
      discoloration accounted for 13.04%. CONCLUSIONS: The steroid injections showed to
      be an alternative excellent treatment for UBC, with complete healing of the
      lesions in the majority of cases. This procedure is not expensive, mini-invasive,
      with low surgical risk and short hospitalization.

PMID- 23549914
TI  - [Mycosis fungoides or inflammatory dermatitis: differential diagnosis between
      early lymphoma and inflammation in skin biopsies].
AB  - Mycosis fungoides is a cutaneous T-cell lymphoma with protracted clinical course
      and progression in different stages with increasing aggressiveness. The clinical
      picture as well as the histopathology of mycosis fungoides within the early patch
      and plaque phase is difficult to delineate from some inflammatory skin diseases.
      Thus, the diagnosis of these early stages of the lymphoma is only possible when
      clinical, histopathological, and molecular features are integrated into the
      diagnosis, especially as none of the individual disease criteria is specific.
      Important clues towards the diagnosis of mycosis fungoides are cytologically
      abnormal epidermotropic CD4-positive T-cells causing only minor epidermal
      alterations, the formation of Pautrier-abscesses and basal alignment of the
      epidermotropic T-cells. The findings of an aberrant T-cell immunophenotype of the
      intraepidermal lymphoid component as well as the molecular proof of T-cell
      clonality are important further features. In the differential diagnosis between
      early stage mycosis fungoides and parapsoriasis, there remains nevertheless a
      diagnostic and maybe also a true biological grey zone.

PMID- 23549915
TI  - Structure of a protozoan virus from the human genitourinary parasite Trichomonas
      vaginalis.
AB  - The flagellated protozoan Trichomonas vaginalis is an obligate human
      genitourinary parasite and the most frequent cause of sexually transmitted
      disease worldwide. Most clinical isolates of T. vaginalis are persistently
      infected with one or more double-stranded RNA (dsRNA) viruses from the genus
      Trichomonasvirus, family Totiviridae, which appear to influence not only
      protozoan biology but also human disease. Here we describe the three-dimensional
      structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by
      electron cryomicroscopy and icosahedral image reconstruction. The structure
      reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent
      positions, designated A and B, as previously observed for fungal Totiviridae
      family members. The putative protomer is identified as an asymmetric AB dimer
      consistent with either decamer or tetramer assembly intermediates. The capsid
      surface is notable for raised plateaus around the icosahedral 5-fold axes, with
      canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold
      axes are unusually wide and may facilitate release of the viral genome, promoting
      dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure
      of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or
      purified TVV1 virions. Despite extensive sequence divergence, conservative
      features of the capsid reveal a helix-rich fold probably derived from an ancestor
      shared with fungal Totiviridae family members. Also notable are mass spectrometry
      results assessing the virion proteins as a complement to structure determination,
      which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion
      with its capsid protein involves -2, and not +1, ribosomal frameshifting, an
      uncommonly found mechanism to date.

PMID- 23549916
TI  - Rapid detection of HIV-1 proviral DNA for early infant diagnosis using
      recombinase polymerase amplification.
AB  - Early diagnosis and treatment of human immunodeficiency virus type 1 (HIV-1)
      infection in infants can greatly reduce mortality rates. However, current infant
      HIV-1 diagnostics cannot reliably be performed at the point of care, often
      delaying treatment and compromising its efficacy. Recombinase polymerase
      amplification (RPA) is a novel technology that is ideal for an HIV-1 diagnostic,
      as it amplifies target DNA in <20 min at a constant temperature, without the need
      for complex thermocycling equipment. Here we tested 63 HIV-1-specific primer and
      probe combinations and identified two RPA assays that target distinct regions of
      the HIV-1 genome (long terminal repeat [LTR] and pol) and can reliably detect 3
      copies of proviral DNA by the use of fluorescence detection and lateral-flow
      strip detection. These pol and LTR primers amplified 98.6% and 93%, respectively,
      of the diverse HIV-1 variants tested. This is the first example of an isothermal
      assay that consistently detects all of the major HIV-1 global subtypes.

PMID- 23549917
TI  - Complement component 3C3 and C3a receptor are required in chitin-dependent
      allergic sensitization to Aspergillus fumigatus but dispensable in chitin-induced
      innate allergic inflammation.
AB  - Levels of the anaphylatoxin C3a are increased in patients with asthma compared
      with those in nonasthmatics and increase further still during asthma
      exacerbations. However, the role of C3a during sensitization to allergen is
      poorly understood. Sensitization to fungal allergens, such as Aspergillus
      fumigatus, is a strong risk factor for the development of asthma. Exposure to
      chitin, a structural polysaccharide of the fungal cell wall, induces innate
      allergic inflammation and may promote sensitization to fungal allergens. Here, we
      found that coincubation of chitin with serum or intratracheal administration of
      chitin in mice resulted in the generation of C3a. We established a model of
      chitin-dependent sensitization to soluble Aspergillus antigens to test the
      contribution of complement to these events. C3(-/-) and C3aR(-/-) mice were
      protected from chitin-dependent sensitization to Aspergillus and had reduced lung
      eosinophilia and type 2 cytokines and serum IgE. In contrast, complement
      deficient mice were not protected against chitin-induced innate allergic
      inflammation. In sensitized mice, plasmacytoid dendritic cells from complement
      deficient animals acquired a tolerogenic profile associated with enhanced
      regulatory T cell responses and suppressed Th2 and Th17 responses specific for
      Aspergillus. Thus, chitin induces the generation of C3a in the lung, and chitin
      dependent allergic sensitization to Aspergillus requires C3aR signaling, which
      suppresses regulatory dendritic cells and T cells and induces allergy-promoting T
      cells.

PMID- 23549918
TI  - Powerful genetic resource for the study of methicillin-resistant Staphylococcus
      aureus.
AB  - In "A Genetic resource for Rapid and Comprehensive Phenotype Screening of
      Nonessential Staphylococcus aureus Genes" (mBio 4(2):e00537-12, doi:
      10.1128/mBio.00537-12, 2013), Fey et al. describe the creation and application of
      a defined transposon mutant library of methicillin-resistant S. aureus. This
      library is well organized and made accessible to the research community through
      an easily navigable central repository. The mutant library promises to be a
      significant resource for researchers seeking a greater understanding of this
      pathogen.

PMID- 23549919
TI  - Bacterial bioluminescence regulates expression of a host cryptochrome gene in the
      squid-Vibrio symbiosis.
AB  - The symbiosis between the squid Euprymna scolopes and its luminous symbiont,
      Vibrio fischeri, is characterized by daily transcriptional rhythms in both
      partners and daily fluctuations in symbiont luminescence. In this study, we
      sought to determine whether symbionts affect host transcriptional rhythms. We
      identified two transcripts in host tissues (E. scolopes cry1 [escry1] and escry2)
      that encode cryptochromes, proteins that influence circadian rhythms in other
      systems. Both genes cycled daily in the head of the squid, with a pattern similar
      to that of other animals, in which expression of certain cry genes is entrained
      by environmental light. In contrast, escry1 expression cycled in the symbiont
      colonized light organ with 8-fold upregulation coincident with the rhythms of
      bacterial luminescence, which are offset from the day/night light regime.
      Colonization of the juvenile light organ by symbionts was required for induction
      of escry1 cycling. Further, analysis with a mutant strain defective in light
      production showed that symbiont luminescence is essential for cycling of escry1;
      this defect could be complemented by presentation of exogenous blue light.
      However, blue-light exposure alone did not induce cycling in nonsymbiotic
      animals, but addition of molecules of the symbiont cell envelope to light-exposed
      animals did recover significant cycling activity, showing that light acts in
      synergy with other symbiont features to induce cycling. While symbiont
      luminescence may be a character specific to rhythms of the squid-vibrio
      association, resident microbial partners could similarly influence well
      documented daily rhythms in other systems, such as the mammalian gut.

PMID- 23549922
TI  - Comparison of Densiron 68 and 1 000 cSt silicone oil in the management of
      rhegmatogenous retinal detachment with inferior breaks.
AB  - AIM: To compare success rates and complications of Densiron 68 and 1000cSt
      silicone oil (SO) in the management of rhegmatogenous retinal detachment (RRD)
      with inferior breaks (IBs). METHODS: Totally 61 eyes of 61 consecutive patients
      with RRD with IBs were assigned to pars plana vitrectomy (PPV) with Densiron
      (n=31) or PPV with SO (n=30) in order of presentation. SO and Densiron removal
      was performed 3 months after initial surgery. Follow up visits were terminated 6
      months after SO removal. RESULTS: With a single operation, the Densiron group
      showed 84% and SO 74% reattachment. With further surgery, both groups showed 90%
      re-attachment. Complications such as cataract, raised intraocular pressure (IOP),
      inflammatory reaction, macular epiretinal membranes, and emulsification of SO
      were seen in both groups. CONCLUSION: Densiron and SO are found to have similar
      success rates and complications.

PMID- 23549923
TI  - Monitoring intracellular, interstitial, and intravascular volume changes during
      fluid management procedures.
AB  - The bioimpedance spectroscopic (BIS) analytical algorithm described in this
      report allows for the non-invasive measurement of intravascular, interstitial,
      and intracellular volume changes during various fluid management procedures. The
      purpose of this study was to test clinical use feasibility and to demonstrate the
      validity of the BIS algorithm in computing compartmental volume shifts in human
      subjects undergoing fluid management treatment. Validation was performed using
      volume changes recorded from 20 end stage renal disease patients. The validation
      procedure involved mathematically deriving post hoc hematocrit profiles from the
      BIS data-generated fluid redistribution time profiles. These derived hematocrit
      profiles were then compared to serial hematocrit values measured simultaneously
      by a CritLine((r)) monitor during 60 routine hemodialysis sessions. Regression
      and Bland-Altman analyses confirm that the BIS algorithm can be used to reliably
      derive the continuous and real-time rates of change of the compartmental fluid
      volumes. Regression results yielded a R (2) > 0.99 between the two measures of
      hematocrit at different times during dialysis. The slopes of the regression
      equations at the different times were nearly identical, demonstrating an almost
      one-to-one correspondence between the BIS and CritLine((r)) hematocrits. Bland
      Altman analysis show that the BIS algorithm can be used interchangeably with the
      CritLine((r)) monitor for the measurement of hematocrit. The present study
      demonstrates for the first time that BIS can provide real-time continuous
      measurements of compartmental intravascular, interstitial and intracellular fluid
      volume changes during fluid management procedures when used in conjunction with
      this new algorithm. 

PMID- 23549924
TI  - The effect of aortic wall and aortic leaflet stiffening on coronary hemodynamic:
      a fluid-structure interaction study.
AB  - Pathologies of the aortic valve such as aortic sclerosis are thought to impact
      coronary blood flow. Recent clinical investigations have observed simultaneous
      structural and hemodynamic variations in the aortic valve and coronary arteries
      due to regional pathologies of the aortic valve. The goal of the present study is
      to elucidate this observed and yet unexplained phenomenon, in which a local
      pathology in the aortic valve region could potentially lead to the initiation or
      progression of coronary artery disease. Results revealed a considerable impact on
      the coronary flow, velocity profile, and consequently shear stress due to an
      increase in the aortic wall or aortic leaflet stiffness and thickness which
      concur with clinical observations. The cutoff value of 0.75 for fractional flow
      reserve was reached when the values of leaflet thickness and aortic wall
      stiffness were approximately twice and three times their normal value,
      respectively. Variations observed in coronary velocity profiles as well as wall
      shear stress suggest a possible link for the initiation of coronary artery
      disease. 

PMID- 23549926
TI  - Interfacial interaction between methyl parathion-degrading bacteria and minerals
      is important in biodegradation.
AB  - In the present study, the influence of kaolinite and goethite on microbial
      degradation of methyl parathion was investigated. We observed that the
      biodegradation process was improved by kaolinite and depressed by goethite.
      Calorimetric data further showed that the metabolic activities of degrading cells
      (Pseudomonas putida) were enhanced by the presence of kaolinite and depressed by
      the presence of goethite. A semipermeable membrane experiment was performed and
      results supported the above observations: the promotive effect of kaolinite and
      the inhibition of goethite for microbial degradation was not found when the
      bacteria was enclosed by semipermeable membrane and had no direct contact with
      these minerals, suggesting the important function of the contact of cellular
      surfaces with mineral particles. The relative larger particles of kaolinite were
      loosely attached to the bacteria. This attachment made the cells easy to use the
      sorbed substrate and then stimulated biodegradation. For goethite, small
      particles were tightly bound to bacterial cells and limited the acquisition of
      substrate and nutrients, thereby inhibiting biodegradation. These results
      indicated that interfacial interaction between bacterial cells and minerals
      significantly affected the biodegradation of pesticides. 

PMID- 23549927
TI  - Mapping CushingQoL scores onto SF-6D utility values in patients with Cushing's
      syndrome.
AB  - OBJECTIVES: To construct a prediction model of preference-adjusted health status
      (SF-6D) for Cushing's syndrome using a disease-specific health-related quality of
      life (HRQOL) measure (CushingQoL). METHODS: Data were obtained from the original
      multicenter, multinational study to validate the CushingQoL questionnaire. HRQOL
      was measured using the CushingQoL and the SF-36 questionnaires. SF-6D scores were
      calculated from responses on the SF-36. Sociodemographic and clinical data were
      also collected. Various predictive models were tested and the final one was
      selected on the basis of four criteria: explanatory power, consistency of
      estimated coefficients, normality of prediction errors, and parsimony. RESULTS:
      For the mapping analysis, data were available from 116 of the 125 patients
      included in the original validation study. Mean (SD) age was 45.3 (13.1) years
      and the sample was predominantly (83 %) female. Patients had a mean (SD)
      CushingQoL score of 52.9 (21.9), whereas the SF-6D (derived from SF-36) was
      skewed towards better health with a mean of 0.71 (median 0.74) on a scale of 
      0.704 to 1. Of the various models tested, a model which included the intercept
      (0.61), CushingQoL overall score, level one in CushingQoL item 2 (always have
      pain preventing me from leading a normal life), and level one in CushingQoL item
      10 (my illness always affects my everyday activities) best met the four criteria
      for model selection. The model had an adjusted R (2) of 0.60 and a root mean
      square error of 0.084. CONCLUSIONS: Although the mapping function finally
      selected appears to be able to accurately map CushingQoL scores onto SF-6D
      outcomes at the group level, further testing is required to validate the model in
      independent patient samples.

PMID- 23549928
TI  - Ranking sources of hospital quality information for orthopedic surgery patients:
      consequences for the system of managed competition.
AB  - BACKGROUND: Healthcare quality information is crucial for the system of managed
      competition. Within a system of managed competition, health insurers can
      selectively contract care providers and are allowed to channel patients towards
      contracted providers. The idea is that insurers have a stronger bargaining
      position compared to care providers when they are able to channel patients. In
      the Dutch system of managed competition that was implemented in 2006, channelling
      patients to preferred providers has not yet been very successful. Empirical
      knowledge of which sources of hospital quality information they find important
      may help us to understand how to channel patients to preferred providers.
      OBJECTIVES: The objective of this survey was to measure how patients rank various
      sources of information when they compare hospital quality in a system of managed
      competition. METHODS: A written survey was conducted among clients of a large
      Dutch health insurance company. These clients underwent orthopedic surgery on the
      hip or knee no longer than 12 months ago. RESULTS: Two major players within a
      system of managed competition-health insurers and the government-were not seen as
      important sources of hospital quality information. In contrast, own experience
      and general practitioners (GPs) were seen as the most important sources of
      hospital quality information within the Dutch system of managed competition.
      CONCLUSIONS: Health insurers should take the main finding-that GPs are the most
      important source of hospital quality information-into account when they contract
      care providers and develop strategies for channeling patients towards preferred
      providers. A well-functioning system of managed competition will benefit
      patients, as it involves incentives for care providers to increase healthcare
      quality and to produce at the lowest cost per unit of quality.

PMID- 23549929
TI  - Community-acquired pneumonia: symptoms and burden of illness at diagnosis among
      US adults aged 50 years and older.
AB  - PURPOSE: Community-acquired pneumonia (CAP) is a leading cause of morbidity and
      mortality in older adults, yet few studies have comprehensively measured the
      burden of CAP symptoms and their impact from the patient perspective. Our Web
      survey used the newly developed CAP burden of illness questionnaire (CAP-BIQ)
      designed to assess the presence of key symptoms, comorbid conditions affected by
      CAP, psychosocial impacts, productivity, and CAP-associated physician visits in
      US adults aged 50 years and older. METHODS: The CAP-BIQ was developed from semi
      structured one-on-one interviews and finalized after cognitive debriefings with
      recently diagnosed CAP patients. The CAP-BIQ was then administered to 500 survey
      participants with a CAP diagnosis within the past 120 days confirmed by chest
      imaging recruited from a Web-based panel. Analyses of survey results were
      weighted for national representativeness, and were compared between relevant age,
      hospitalization status, and pneumonia-risk subgroups. RESULTS: The survey
      participants' mean age was 62.4 years; 45 % were men; and 39.6 % were
      hospitalized due to CAP. On average, the surveys were completed 56.9 days after
      pneumonia diagnosis. Nearly all participants reported tiredness, cough, body
      aches, weakness, shortness of breath, wheezing, and a weak appetite at the time
      of diagnosis (99.0, 96.8, 96.9, 94.1, 89.1, 85.8, and 78.5 %, respectively).
      There was generally greater symptom prevalence at diagnosis in younger,
      nonhospitalized, or high-risk subgroups when compared to their respective older,
      hospitalized, or low-risk counterparts. Most participants reported at least one
      cough-related and weakness-related impact on their daily life and activities from
      CAP. Over three quarters of the respondents (77.4 %) needed assistance from a
      friend or family member during their bout with pneumonia and a majority of
      respondents (83.6 %) were satisfied with the care they received from their
      doctors across the course of their illness. CONCLUSIONS: This study
      systematically assessed CAP symptoms and their impacts using the CAP-BIQ, a
      questionnaire with established content validity. At CAP diagnosis, the range of
      patient-reported symptoms was broader than previous studies have reported.
      Additionally, the overwhelming need for caregiver assistance demonstrates the
      burden this illness places on older adults.

PMID- 23549931
TI  - Lectin array analysis for wild-type and alpha-Gal-knockout pig islets versus
      healthy human islets.
AB  - PURPOSE: We performed lectin microarray analyses of islets from wild-type (WT)
      pigs and alpha1-3galactosyltransferase gene knockout (GKO) pigs and compared the
      results with the corresponding values for islets from healthy humans. METHODS:
      Islets were isolated from the pancreas. After sonication and centrifugation, the
      proteins in the supernatant from each islet were labeled with Cy3 and applied to
      a lectin array. RESULTS: Despite negligible expression of the Gal antigen on the
      adult pig islets (APIs), GKO-islets showed weaker signals, not only for GS-I-B4
      but also for PNA, WFA, PTL-I, and GS-I-A4, than the WT islets, indicating reduced
      contents of alpha-linked GalNAc and Galbeta1-3GalNAc. In comparing the islets of
      pigs vs. humans, human islets showed stronger signals for UEA-I, AAL, TJA-II,
      EEL, WFA, HPA, DBA, SBA and PTL-I, indicating that besides ABO blood type
      antigens, high levels of fucose and alpha-linked GalNAc are present. On the other
      hand, the high mannose form was very rich in the APIs. CONCLUSION: GKO reduced
      alpha-linked GalNAc, despite negligible expression of the Gal antigen on WT-API.
      On the other hand, the high-mannose form was richer in both APIs than in healthy
      human islets. These results provide useful information for future studies.

PMID- 23549930
TI  - Multifocal lesions with pancreatic atrophy in IgG4-related autoimmune
      pancreatitis: report of a case.
AB  - We herein report a case of IgG4-related autoimmune pancreatitis (AIP). A 72-year
      old male with jaundice visited our hospital complaining of epigastralgia. A blood
      chemistry analysis revealed elevated serum levels of total bilirubin and DUPAN
      II. Computed tomography (CT) revealed irregularly shaped pancreatic masses with a
      stricture of the main pancreatic duct (MPD) in the head and tail that were
      interposed by marked atrophy with MPD dilation in the body. F-18
      fluorodeoxyglucose (FDG)-positron emission tomography/CT revealed abnormally
      intense FDG uptake only at the masses. During surgery, another small tumor was
      also found in the atrophied body; therefore, a total pancreatectomy was performed
      under the diagnosis of multiple pancreatic cancers. The histological analysis
      revealed fibrosis with dense and diffuse infiltrations of lymphocytes and IgG4
      positive plasma cells. The pancreatic parenchyma of the body was firmly replaced
      by fibrosis. AIP can lead to the formation of multiple pancreatic lesions, and
      thus the correct diagnosis is occasionally difficult to establish in atypical
      cases. 

PMID- 23549932
TI  - Clinical outcomes after internal iliac artery embolization prior to endovascular
      aortic aneurysm repair.
AB  - PURPOSE: The success of endovascular aortic aneurysm repair (EVAR) is highly
      dependent on the anatomical features of the aneurysm. In order to prevent type II
      endoleaks from the internal iliac artery (IIA), embolization of one or both IIAs
      may be required. METHODS: We performed a retrospective study of a prospectively
      gathered database of 100 patients who underwent EVAR at our institution. The case
      notes were examined, and patients were interviewed by telephone and specifically
      asked about symptoms of pelvic ischemia that they had experienced since
      undergoing EVAR. RESULTS: We identified 42 (42 %) patients who had undergone coil
      embolization of one or both IIAs in preparation for EVAR. The mean time from
      surgery to the follow-up telephone interview was 21.5 months. Buttock
      claudication occurred in 10 (26 %) of 38 patients. Sexual dysfunction occurred in
      13 of 36 male patients (36 %). Age was associated with buttock claudication and
      sexual dysfunction. CONCLUSION: Based on our experience, IIA embolization prior
      to EVAR is not a benign procedure. It can lead to numerous effects associated
      with pelvic ischemia, such as buttock claudication and sexual dysfunction. It is
      necessary to preserve both internal iliac arteries if possible, especially in
      young patients.

PMID- 23549934
TI  - Risk of fracture with thiazolidinediones: an individual patient data meta
      analysis.
AB  - BACKGROUND: The use of thiazolidinediones (TZDs) has been associated with
      increased fracture risks. Our aim was to estimate the risk of fracture with TZDs
      in three different healthcare registries, using exactly the same study design,
      and to perform an individual patient data meta-analysis of these three studies.
      METHODS: Population-based cohort studies were performed utilizing the British
      General Practice Research Database (GPRD), the Dutch PHARMO Record Linkage System
      (RLS), and the Danish National Health Registers. In all three databases, the
      exposed cohort consisted of all patients (aged 18+) with at least one
      prescription of antidiabetic (AD) medication. Cox proportional hazards models
      were used to estimate hazard ratios (HRs) of fracture. The total period of follow
      up for each patient was divided into periods of current exposure and past
      exposure, with patients moving between current and past use. RESULTS: In all
      three registries, the risk of fracture was increased for women who were exposed
      to TZDs: HR 1.48 (1.37-1.60) in GPRD, HR 1.35 (1.15-1.58) in PHARMO, and HR 1.22
      (1.03-1.44) in Denmark. Combining the data in an individual patient data meta
      analysis resulted, for women, in a 1.4-fold increased risk of any fracture for
      current TZD users versus other AD drug users [adj. HR 1.44 (1.35-1.53)]. For men,
      there was no increased fracture risk [adj. HR 1.05 (0.96-1.14)]. Risks were
      increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle, and
      foot, but not for hip/femur or vertebral fractures. Current TZD users with more
      than 25 TZD prescriptions ever before had a 1.6-fold increased risk of fracture
      compared with other AD drug users [HR 1.59 (1.46-1.74)]. CONCLUSION: In this
      study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for
      women using TZDs, but not for men, across three different healthcare registries.
      TZD users had an increased risk for fractures of the extremities, and risks
      further increased for prolonged users of TZDs.

PMID- 23549935
TI  - Preliminary evaluation of an MRI-based technique for displaying and quantifying
      bony deformities in cam-type femoroacetabular impingement.
AB  - PURPOSE: Characterizing aspheric deformities of the femoral head-neck junction in
      cam-type femoroacetabular impingement (FAI) requires representing the location,
      size, or extent of the bony lesion. The objectives of this work are to (1) assess
      the feasibility of creating 3D models of cam deformities from MRI sets, (2)
      present a standardized 2D visualization of the lesion, and (3) present and
      evaluate the potential utility of summary metrics in distinguishing between FAI
      patients and control subjects. METHODS: Using MRIs from five subjects with
      diagnosed cam-type FAI and four healthy subjects, we developed a technique based
      on subtracting an estimated normal surface from each subject's actual bone
      surface in order to generate a subject-specific 2D "diagnosis graph" that
      characterized the femoral deformity. The models from three control subjects were
      combined to create the baseline model. RESULTS: The RMS fitting error between the
      surface models of individual control subjects and their corresponding baseline
      models was 1.05 mm across the head and the head-to-neck transition region. In the
      anterosuperior region of the 2D diagnosis graphs, the mean height of the detected
      cam deformities relative to the estimated baseline normal shape was 17.9 % of the
      head radius for the five FAI subjects (95 % CI 8.5-27.3 %) and 7.0 % (95 % CI 2.9
      11.1 %) for the four control subjects. A binary logistic regression analysis
      indicated that an h/r ratio larger than a threshold of [Formula: see text] = 10.7
      % (equivalent to approximately 2.3 mm in height) yielded the best discrimination
      between cam-type FAI subjects and normal subjects. CONCLUSIONS: Our 2D diagnosis
      graph qualitatively enabled the cam-type lesions in four of our five diagnosed
      patients to be clearly visualized on MRI-derived models. We believe this
      visualization tool may be helpful in better characterizing cam-type lesions for
      diagnosis and for developing more precise plans for surgical treatment.

PMID- 23549936
TI  - Midgut volvulus caused by mesenteric lipoma.

PMID- 23549937
TI  - Clinical staging in psychiatry: a cross-cutting model of diagnosis with heuristic
      and practical value.
AB  - Staging models are used routinely in general medicine for potentially serious or
      chronic physical disorders such as diabetes, arthritis and cancers, describing
      the links between biomarkers, clinical phenotypes and disease extension, and
      promoting a personalised or stratified medicine approach to treatment planning.
      Clinical staging involves a detailed description of where an individual exists on
      a continuum of disorder progression from stage 0 (an at-risk or latency stage)
      through to stage IV (late or end-stage disease). The approach is popular owing to
      its clinical utility and is increasingly being applied in psychiatry. The concept
      offers an informed approach to research and the active promotion of indicated
      prevention and early intervention strategies. We suggest that for young persons
      with emerging bipolar disorder, such transdiagnostic staging models could provide
      a framework that better reflects the developmental psychopathology and matches
      the complex longitudinal inter-relationships between subsyndromal and syndromal
      mood, psychotic and other disorders.

PMID- 23549933
TI  - Usual and unusual development of the dicot leaf: involvement of transcription
      factors and hormones.
AB  - Morphological diversity exhibited by higher plants is essentially related to the
      tremendous variation of leaf shape. With few exceptions, leaf primordia are
      initiated postembryonically at the flanks of a group of undifferentiated and
      proliferative cells within the shoot apical meristem (SAM) in characteristic
      position for the species and in a regular phyllotactic sequence. Auxin is
      critical for this process, because genes involved in auxin biosynthesis,
      transport, and signaling are required for leaf initiation. Down-regulation of
      transcription factors (TFs) and cytokinins are also involved in the light
      dependent leaf initiation pathway. Furthermore, mechanical stresses in SAM
      determine the direction of cell division and profoundly influence leaf initiation
      suggesting a link between physical forces, gene regulatory networks and
      biochemical gradients. After the leaf is initiated, its further growth depends on
      cell division and cell expansion. Temporal and spatial regulation of these
      processes determines the size and the shape of the leaf, as well as the internal
      structure. A complex array of intrinsic signals, including phytohormones and TFs
      control the appropriate cell proliferation and differentiation to elaborate the
      final shape and complexity of the leaf. Here, we highlight the main determinants
      involved in leaf initiation, epidermal patterning, and elaboration of lamina
      shape to generate small marginal serrations, more deep lobes or a dissected
      compound leaf. We also outline recent advances in our knowledge of regulatory
      networks involved with the unusual pattern of leaf development in epiphyllous
      plants as well as leaf morphology aberrations, such as galls after pathogenic
      attacks of pests.

PMID- 23549938
TI  - The balanced care model: the case for both hospital- and community-based mental
      healthcare.
AB  - The balanced care model proposes that a comprehensive mental health system needs
      to include both community- and hospital-based care. The model is based on a
      structured review of scientific evidence, and is also informed by the experience
      of experts active in mental health system change in many countries worldwide.

PMID- 23549939
TI  - Can early intervention services modify pathways into care?
AB  - Pathways into care have not changed significantly since the introduction of early
      intervention services for psychosis in London. Some groups have different
      pathways into care and those whose pathway originates in primary care have a
      longer route to services. This editorial explores the nature of these challenges,
      for both early intervention services and referring agencies.

PMID- 23549940
TI  - Antidepressants and rapid-cycling bipolar II disorder: dogma, definitions and
      deconstructing discrepant data.
AB  - It is suggested that a finding that apparently challenges current practice
      guidelines, namely that patients with a rapid-cycling pattern of bipolar disorder
      can take antidepressant monotherapy for months without increasing risk of
      cycling, may be parsimoniously understood by the way that the investigators
      defined rapid cycling and by their use of acute-phase fluoxetine monotherapy
      prior to randomisation to continutaion-phase therapy with fluoxetine, lithium or
      placebo.

PMID- 23549942
TI  - Invited commentary on . . . Ethnic variations in pathways into early intervention
      services for psychosis.
AB  - Advocates of early intervention in psychosis choose to treat the association
      between long duration of untreated psychosis (DUP) and poor outcome as evidence
      that reducing DUP will improve outcomes. I question this view and argue that DUP
      does not predict outcome but rather that mode of onset of psychosis predicts DUP
      and outcome.

PMID- 23549941
TI  - Effect of psychosocial interventions on social functioning in depression and
      schizophrenia: meta-analysis.
AB  - BACKGROUND: Psychosocial interventions may contribute to reducing the burden of
      mental disorders in low- and middle-income (LAMI) countries by improving social
      functioning, but the evidence has not been systematically reviewed. AIMS:
      Systematic review and meta-analysis of the effect of psychosocial interventions
      on social functioning in people with depression and schizophrenia in LAMI
      countries. METHOD: Studies were identified through database searching up to March
      2011. Randomised controlled trials were included if they compared the
      intervention group with a control group receiving placebo or treatment as usual.
      Random effects meta-analyses were performed separately for depressive disorders
      and schizophrenia and for each intervention type. RESULTS: Of the studies that
      met the inclusion criteria (n = 24), 21 had sufficient data to include in the
      meta-analysis. Eleven depression trials showed good evidence for a moderate
      positive effect of psychosocial interventions on social functioning (standardised
      mean difference (SMD) = 0.46, 95% CI 0.24-0.69, n = 4009) and ten schizophrenia
      trials showed a large positive effect on social functioning (SMD = 0.84, 95% CI
      0.49-1.19, n = 1671), although seven of these trials were of low quality.
      Excluding these did not substantially affect the size or direction of effect,
      although the precision of the estimate was substantially reduced (SMD = 0.89, 95%
      CI 0.05-1.72, n = 863). CONCLUSIONS: Psychosocial interventions delivered in out
      patient and primary care settings are effective at improving social functioning
      in people with depression and should be incorporated into efforts to scale up
      services. For schizophrenia there is an absence of evidence from high-quality
      trials and the generalisabilty of the findings is limited by the over
      representation of trials conducted in populations of hospital patients in China.
      More high-quality trials of psychosocial interventions for schizophrenia
      delivered in out-patient settings are needed.

PMID- 23549943
TI  - Acceptability and necessity of HIV and other blood-borne virus testing in a
      psychiatric setting.
AB  - Studies in North America and Europe indicate that the prevalence of blood-borne
      viruses (BBVs) is elevated in individuals with severe mental illness; there are
      no comparable data for the UK. We offered routine testing for HIV, and hepatitis
      B and C in an inner-London in-patient psychiatric unit as a service improvement.
      Of the patients approached 83% had mental capacity to provide informed consent
      for testing and 66% of patients offered testing accepted. Although it was not our
      objective to establish the prevalence of BBVs, 18% of patients had serological
      evidence of a current or previous BBV infection. We found that offering routine
      testing in an in-patient psychiatric setting is both practical and acceptable to
      patients.

PMID- 23549944
TI  - Link between outcome and service quality is not clear.

PMID- 23549945
TI  - Authors' reply.

PMID- 23549946
TI  - Missing ethnic density data.

PMID- 23549947
TI  - Authors' reply.

PMID- 23549948
TI  - Cardiovascular fitness and serious depression in adulthood.

PMID- 23549949
TI  - Authors' reply.

PMID- 23549950
TI  - New paradigm: developmental psychopathology.

PMID- 23549951
TI  - New paradigm: developmental psychopathology.

PMID- 23549952
TI  - Authors' reply.

PMID- 23549953
TI  - Involvement of IGF-1R regulation by miR-515-5p modifies breast cancer risk among
      BRCA1 carriers.
AB  - Several lines of evidence indicate that sequence alterations within microRNA
      (miRNA)-binding sites can modify the binding to its target gene resulting in
      altered expression patterns. We hypothesized that a single nucleotide
      polymorphism (SNP) located in the miR-515-5p binding site of igf-1r gene may
      alter IGF-1R regulation, with consequent effects on breast cancer risk in BRCA1
      mutation carriers. Computational prediction revealed that the rs28674628 SNP in
      the igf-1r 3' UTR is located within a predicted binding site for miR-515-5p. The
      effect of this SNP on breast cancer risk was evaluated by genotyping 115 Jewish
      Ashkenazi carriers of the 185delAG mutation in the BRCA1 gene using the Sequenom
      platform followed by Kaplan-Meier analysis. Additional data set of 378 Jewish
      BRCA1 carriers was analyzed to validate our results. MiRNA transfection, Western
      blot analysis, luciferase reporter assay, real time PCR, and immunohistochemistry
      were performed to assess direct regulation of igf-1r by miR-515-5p. We show
      direct regulation of IGF-1R by miR-515-5p. We identified that disrupting miR-515
      5p and igf-1r 3' UTR binding by SNP may cause elevated IGF-1R protein levels.
      Interestingly, miR-515-5p is downregulated in tumor tissue compared to its non
      neoplastic surrounding tissue while IGF-1R levels are elevated. This igf-1r SNP
      was found to be significantly associated with age at diagnosis of breast cancer
      in Jewish Ashkenazi BRCA1 mutation carriers. These findings support the
      hypothesis that a SNP located in igf-1r gene may alter miRNA regulation of IGF
      1R, with a putative effect on BRCA1 penetrance and breast cancer risk.

PMID- 23549954
TI  - Pamidronate treatment stimulates the onset of recovery phase reducing fracture
      rate and skeletal deformities in patients with idiopathic juvenile osteoporosis:
      comparison with untreated patients.
AB  - Although spontaneous remission occurs in patients with idiopathic juvenile
      osteoporosis (IJO), permanent bone deformities may occur. The effects of long
      term pamidronate treatment on clinical findings, bone mineral status, and
      fracture rate were evaluated. Nine patients (age 9.8 +/- 1.1 years, 7 males) with
      IJO were randomized to intravenous pamidronate (0.8 +/- 0.1 mg/kg per day for 3
      days; cycles per year 2.0 +/- 0.1; duration 7.3 +/- 1.1 years; n = 5) or no
      treatment (n = 4). Fracture rate, phalangeal quantitative ultrasound, and lumbar
      bone mineral density (BMD) by dual energy X-ray absorptiometry at entry and
      during follow-up (range 6.3-9.4 years) were assessed. Bone pain improved in
      treated patients. Difficulty walking continued for 3-5 years in untreated
      patients, and vertebral collapses occurred in three of them. During follow-up,
      phalangeal amplitude-dependent speed of sound (AD-SoS), bone transmission time
      (BTT), and lumbar BMDarea and BMDvolume progressively increased in treated
      patients (P < 0.05-P < 0.0001). In untreated patients AD-SoS and BTT decreased
      during the first 2-4 years of follow-up (P < 0.05-P < 0.01); lumbar BMDarea
      increased after 6 years (P < 0.001) whereas BTT and lumbar BMDvolume increased
      after 7 years of follow-up (P < 0.05 and P < 0.001, respectively). At the end of
      follow-up, AD-SoS, BTT, lumbar BMDarea, and BMDvolume Z-scores were lower in
      untreated patients than in treated patients (-2.2 +/- 0.3 and -0.5 +/- 0.2; -1.9
      +/- 0.2 and -0.6 +/- 0.2; -2.3 +/- 0.3 and -0.7 +/- 0.3; -2.4 +/- 0.2 and -0.7 +/
      0.3, P < 0.0001, respectively). Fracture rate was higher in untreated patients
      than in treated patients during the first 3 years of follow-up (P < 0.02). Our
      study showed that spontaneous recovery of bone mineral status is unsatisfactory
      in patients with IJO. Pamidronate treatment stimulated the onset of recovery
      phase reducing fracture rate and permanent disabilities without evidence of side
      effects. 

PMID- 23549956
TI  - Healthcare experiences of autistic adults.

PMID- 23549955
TI  - Fatal hemorrhagic stroke in a Caucasian girl with moyamoya disease.
AB  - INTRODUCTION: Moyamoya disease (MMD) is an extremely rare neurovascular disorder
      in Caucasian children. To the best of our knowledge, the aggressive variant
      including hemorrhagic malignant stroke and consecutive global ischemia has not
      been reported for this population before. CASE REPORT: We present the case of an
      11-year-old girl with sudden neurological deterioration due to intracerebral
      hemorrhage with early irruption into the ventricular system. MMD with extensive
      neovascularization was diagnosed by means of computed tomography and magnetic
      resonance imaging. Despite immediate ventricular drainage, intracranial pressure
      increased above the mean arterial pressure resulting in malignant bi-hemispheric
      ischemia. The girl died within 53 h after admission to hospital. DISCUSSION:
      Intracerebral hemorrhage in young patients is often attributed to vascular
      malformation. This case shows that MMD may constitute a potential diagnosis in
      the case of sudden neurological deterioration and loss of consciousness, even in
      previously healthy children.

PMID- 23549957
TI  - Succeeding as a clinician educator: useful tips and resources.

PMID- 23549958
TI  - Community-acquired pneumonia and proton pump inhibitors.

PMID- 23549959
TI  - Social support and cancer incidence and mortality: the JPHC study cohort II.
AB  - BACKGROUND: Studies conducted in Western countries have found a robust
      association between higher social support and improved cancer outcomes,
      particularly for breast cancer incidence and prognosis. However, less is known
      about the influence of social support on cancer among Asian populations where the
      measures of social support may differ in social relationships. In this
      prospective cohort study in Japan, we sought to examine the associations between
      the incidence and mortality of total and site-specific cancer. METHODS: We
      examined prospectively the association between social support and risk of cancer
      incidence and mortality within a cohort of 44,152 Japanese men and women, aged 40
      69 years, free of prior diagnosis of cancer and cardiovascular disease. Social
      support was measured by emotional support defined as receipt of confidant support
      and esteem support from family members or friends and by social isolation. A
      total of 3,444 cases of newly diagnosed cancer and 1,561 cancer deaths occurred
      between the baseline questionnaire (1993-1994) and the end of follow-up in
      January 2004. RESULTS: The multivariate hazard ratios (HR) and 95 % confidence
      intervals for colorectal cancer incidence and mortality in the highest social
      support versus lowest social support group were 1.48 (1.06-2.05) and 3.07 (1.65
      5.69) in men, respectively. Social support was not associated with other site
      specific cancer incidence or cancer outcomes in women. CONCLUSIONS: Low social
      support was associated with higher risk of both colorectal cancer incidence and
      mortality in men. Social support may affect colorectal cancer onset and prognosis
      via a range of factors, including healthier lifestyles as well as adherence to
      therapeutic regimens.

PMID- 23549960
TI  - Taking a closer look: autonomic dysregulation in socially anxious children.
AB  - Previous research on autonomic characteristics of social anxiety in children and
      adolescents has produced highly inconsistent results which may partially be due
      to task differences and a limited breadth of autonomic measurement. Here we
      investigated a sample of high (HSA) and low socially anxious (LSA) children, aged
      10-12 years before, during and after a standardized evaluated speech task while
      acquiring a broad set of autonomic and experiential measures. During baseline, we
      found evidence for tonically higher sympathetic autonomic activity in HSA
      children, indicated by higher low frequency heart rate variability (LF) and a
      trend for higher LF to high frequency heart rate variability ratios (LF/HF). In
      response to the speech task, HSA children showed blunted cardiac responding
      evidenced by slower increase and delayed recovery of heart rate and a similar
      significant trend on LF/HF values. Self-reported anxiety, by contrast, showed
      enhanced reactivity from baseline to anticipation in the HSA compared to the LSA
      group. The results suggest a restricted cardiac flexibility in HSA children and
      illustrate that broad autonomic assessment during a well-structured, naturalistic
      task may improve our understanding of the autonomic physiology of socially
      anxious children. The results have implications for current theories of social
      anxiety.

PMID- 23549961
TI  - Successful implantation of autologous muscle-derived stem cells in treatment of
      faecal incontinence due to external sphincter rupture.

PMID- 23549963
TI  - It's OK to disagree.

PMID- 23549962
TI  - Effects of gastrogastric fistula repair on weight loss and gut hormone levels.
AB  - BACKGROUND: Weight regain after gastric bypass (GBP) can be associated with a
      gastrogastric fistula (GGF), in which a channel forms between the gastric pouch
      and gastric remnant, allowing nutrients to pass through the "old route" rather
      than bypassing the duodenum. To further understand the mechanisms by which GGF
      may lead to weight regain, we investigated gut hormone levels in GBP patients
      with a GGF, before and after repair. MATERIALS AND METHODS: Seven post-GBP
      subjects diagnosed with GGF were studied before and 4 months after GGF repair.
      Another cohort of 22 GBP control subjects without GGF complication were studied
      before and 1 year post-GBP. All subjects underwent a 50-g oral glucose tolerance
      test and blood was collected from 0-120 min for glucose, insulin, ghrelin, PYY3
      36, GIP, and GLP-1 levels. RESULTS: Four months after GGF repair subjects lost
      6.0 +/- 3.9 kg and had significantly increased postprandial PYY3-36 levels. After
      GGF repair, fasting and postprandial ghrelin levels decreased and were strongly
      correlated with weight loss. The insulin response to glucose also tended to be
      increased after GGF repair, however no concomitant increase in GLP-1 was
      observed. Compared to the post-GBP group, GLP-1 and PYY3-36 levels were
      significantly lower before GGF repair; however, after GGF repair, PYY3-36 levels
      were no longer lower than the post-GBP group. CONCLUSIONS: These data utilize the
      GGF model to highlight the possible role of duodenal shunting as a mechanism of
      sustained weight loss after GBP, and lend support to the potential link between
      blunted satiety peptide release and weight regain.

PMID- 23549964
TI  - Evaluation of weight loss on a low-calorie meal replacement diet as a potential
      predictor of weight loss after laparoscopic adjustable gastric banding surgery in
      adolescents.
AB  - BACKGROUND: Predicting weight loss after laparoscopic adjustable gastric banding
      (LAGB) from preoperative factors has been challenging. This study aimed to
      determine the relationship between weight loss from a preoperative low-calorie
      meal replacement diet (LCMRD) and weight loss after LAGB in a cohort of morbidly
      obese adolescents. METHODS: Fifty-one subjects (86 % female, 61 % Caucasian, mean
      age 16 years, mean weight 140.1 kg) received 2 weeks of LCMRD prior to LAGB. We
      utilized Pearson's correlation coefficients to test the relationship between
      weight loss on a LCMRD and weight loss at 3, 6, and 12 months after LAGB.
      RESULTS: Mean weight loss was 5.7 kg (standard deviation (SD) 2.5) during the
      LCMRD period and 17.4 kg (SD 12.4) at 1 year postoperatively. Having a higher
      baseline weight (p < 0.01) and losing less weight prior to LCMRD (p < 0.05) was
      associated with more weight loss during LCMRD. Weight loss during LCMRD was not
      significantly associated with postoperative weight loss at any time point.
      CONCLUSIONS: Weight loss during LCMRD was not significantly associated with
      postoperative weight loss in our study. Less variability in adherence, less
      influence of genetic and biological potential, and more diuresis during a short
      course of LCMRD compared to in the postoperative period may explain this lack of
      association.

PMID- 23549966
TI  - Cardiac complications of influenza infection in 3 adults.

PMID- 23549967
TI  - Thyroid eye disease.

PMID- 23549968
TI  - Oral health researchers form Canadian network.

PMID- 23549969
TI  - Federal budget slammed by health critics.

PMID- 23549970
TI  - Organ donation after death in Ontario: a population-based cohort study.
AB  - BACKGROUND: Shortfalls in deceased organ donation lead to shortages of solid
      organs available for transplantation. We assessed rates of deceased organ
      donation and compared hospitals that had clinical services for transplant
      recipients (transplant hospitals) to those that did not (general hospitals).
      METHODS: We conducted a population-based cohort analysis involving patients who
      died from traumatic brain injury, subarachnoid hemorrhage, intracerebral
      hemorrhage or other catastrophic neurologic conditions in Ontario, Canada,
      between Apr. 1, 1994, and Mar. 31, 2011. We distinguished between acute care
      hospitals with and without transplant services. The primary outcome was actual
      organ donation determined through the physician database for organ procurement
      procedures. RESULTS: Overall, 87,129 patients died from catastrophic neurologic
      conditions during the study period, of whom 1930 became actual donors. Our
      primary analysis excluded patients from small hospitals, reducing the total to
      79,746 patients, of whom 1898 became actual donors. Patients who died in
      transplant hospitals had a distribution of demographic characteristics similar to
      that of patients who died in other large general hospitals. Transplant hospitals
      had an actual donor rate per 100 deaths that was about 4 times the donor rate at
      large general hospitals (5.0 v. 1.4, p < 0.001). The relative reduction in
      donations at general hospitals was accentuated among older patients, persisted
      among patients who were the most eligible candidates and amounted to about 121
      fewer actual donors per year (adjusted odds ratio 0.58, 95% confidence interval
      0.36-0.92). Hospital volumes were only weakly correlated with actual organ
      donation rates. INTERPRETATION: Optimizing organ donation requires greater
      attention to large general hospitals. These hospitals account for most of the
      potential donors and missed opportunities for deceased organ donation.

PMID- 23549971
TI  - New isotope manufacturing methods head for regulatory approval.

PMID- 23549972
TI  - Rare diseases reconsidered.

PMID- 23549974
TI  - Deathless models of aging and the importance of acknowledging the dying process.

PMID- 23549975
TI  - Short-term outcomes of tonsillectomy in adult patients with recurrent
      pharyngitis: a randomized controlled trial.
AB  - BACKGROUND: Limited evidence exists as to the benefit of tonsillectomy in adult
      patients. We sought to determine the short-term efficacy of tonsillectomy for
      recurrent pharyngitis in adults. METHODS: We conducted a randomized, controlled,
      parallel-group trial at a tertiary care ear, throat and nose centre in Oulu,
      Finland, between October 2007 and December 2010. Adult patients with recurrent
      pharyngitis were randomly assigned to the control group (watchful waiting) or the
      tonsillectomy group. Our primary outcome was the difference in the proportion of
      patients with severe pharyngitis (severe symptoms and C-reactive protein level >
      40 mg/L) within 5 months. Our secondary outcomes included differences between
      groups in proportions of patients who had episodes of pharyngitis with or without
      medical consultation, rates of pharyngitis and numbers of days with symptoms.
      RESULTS: Of 260 patients referred for tonsillectomy because of recurrent
      pharyngitis, we recruited 86 participants for our study. Of these, 40 patients
      were randomly allocated to the control group, and 46 were randomly allocated to
      the tonsillectomy group. One patient in the control group and no patients in the
      tonsillectomy group had a severe episode of pharyngitis (difference 3%, 95%
      confidence interval [CI] -2% to 7%). Seventeen patients in the control group
      (43%) and 2 patients in the tonsillectomy group (4%) consulted a physician for
      pharyngitis (difference 38%, 95% CI 22% to 55%). Overall, 32 patients in the
      control group (80%) and 18 patients in the tonsillectomy group (39%) had an
      episode of pharyngitis during the 5-month follow-up (difference 41%, 95% CI 22%
      to 60%). The rate of pharyngitis and number of symptomatic days were
      significantly lower in the tonsillectomy group than in the control group.
      INTERPRETATION: There was no significant difference in the number of episodes of
      severe pharyngitis between the control and treatment groups, and episodes were
      rare. However, tonsillectomy resulted in fewer symptoms of pharyngitis,
      consequently decreasing the number of medical visits and days absent from school
      or work. For this reason, surgery may benefit some patients. TRIAL REGISTRATION:
      ClinicalTrials.gov, no. NCT00547391.

PMID- 23549976
TI  - Systematic review wins CMAJ Bruce Squires Award.

PMID- 23549977
TI  - Participation of aquaporin-1 in vascular changes and remodeling in cirrhotic
      liver.
AB  - The pathophysiology of arterial capillary proliferation accompanying fibrosis in
      human cirrhosis remains unclear. However, evidence regarding the molecules
      participating in the pathophysiological process has been accumulating. Water
      channel proteins known as aquaporins (AQP)s, notably AQP-1, appear to be involved
      in the arterial capillary proliferation in the cirrhotic liver. 

PMID- 23549978
TI  - 3-Hydroxyl-3-methylglutaryl-coenzyme A reductase is up regulated in
      hepatocellular carcinoma associated with paraneoplastic hypercholesterolemia.
AB  - Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic
      hypercholesterolemia. However, cholesterol overproduction in HCC tissue has never
      been demonstrated. An aim of this study is to prove cholesterol overproduction in
      the HCC tissue of patients with paraneoplastic hypercholesterolemia. Six patients
      with HCC associated with paraneoplastic hypercholesterolemia and three control
      patients with HCC who did not have hypercholesterolemia were investigated
      regarding the expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase in HCC tissue by means of immunohistochemical technique. In HCC
      associated with paraneoplastic hypercholesterolemia, HMG-CoA reductase was
      clearly stained in cancer cells whereas surrounding non-tumorous hepatocytes
      showed only slight expression of HMG-CoA reductase. In contrast, HCC tissues
      derived from patients without paraneoplastic hypercholesterolemia showed only
      slight expression of HMG-CoA reductase whereas surrounding non-tumorous
      hepatocytes showed a clear expression of HMG-CoA reductase. We morphologically
      proved cholesterol overproduction in HCC tissue derived from patients with
      paraneoplastic hypercholesterolemia. Immunohistochemistry for HMG-CoA reductase
      thought to be useful in the diagnosis of paraneoplastic hypercholesterolemia. 

PMID- 23549979
TI  - Characterization of articular chondrocytes isolated from 211 osteoarthritic
      patients.
AB  - We analyzed specific features of chondrocytes as cellular yield, cell doubling
      rates and the dependence between these parameters and patient-related data in a
      set of 211 osteoarthritic (OA) patients undergoing total joint replacement. For
      each patient the data available were joint type, age and gender. Knee samples
      chosen randomly among all biopsies were graded according to ICRS score. Patients'
      age ranged between 30 and 90 years with a mean age of 66 +/- 9.7 years. Patients
      were divided into age classes and statistically significant differences in
      proliferation rate at passage 1 were found between chondrocytes derived from
      young and old donors, with the last ones characterized by a lower proliferation
      rate. A similar trend was observed for proliferation rate at passage 2. For all
      the samples, cellular yields ranged between 0.1 and 5.5 million cells/g of
      tissue. No significant correlation was observed between the level of cartilage
      degeneration (ICRS score) and cellular yield and proliferation rates. However, in
      samples with a high degree of cartilage degeneration (ICRS score 4) the cellular
      yield was lower compared to the other three groups (ICRS scores 1-3). In this
      study we performed a systematic characterization of basic parameters of
      chondrocytes originating from a wide group of OA patients. Considering the use of
      autologous chondrocytes in chondral treatments, the characterization of cell
      basic features may represent an important step to determine the quality of the
      cell source which is a major determinant in the outcome of cell-based therapies.

PMID- 23549981
TI  - A highly sensitive and accurate method to quantify absolute numbers of c-kit+
      cardiac stem cells following transplantation in mice.
AB  - Although transplantation of c-kit+ cardiac stem cells (CSCs) alleviates post
      myocardial infarction left ventricular dysfunction, there are no reliable methods
      that enable measurement of the absolute number of CSCs that persist in the
      recipient heart. To overcome this limitation, we developed a highly sensitive and
      accurate method to quantify the absolute number of murine CSCs after
      transplantation. This method has two unique features: (1) real-time PCR-based
      detection of a novel male-specific, multiple-copy gene, Rbmy, which significantly
      increases the sensitivity of detection of male donor cells in a female recipient,
      and (2) an internal standard, which permits quantification of the absolute number
      of CSCs as well as the total number of cells in the recipient organ. Female
      C57BL/6 mice underwent coronary occlusion and reperfusion; 2 days later, 10(5)
      male mouse CSCs were injected intramyocardially. Tissues were analyzed by real
      time PCR at serial time points. In the risk region, >75 % of CSCs present at 5
      min were lost in the ensuing 24 h; only 7.6 +/- 2.1 % of the CSCs present at 5
      min could still be found at 7 days after transplantation and only 2.8 +/- 0.5 %
      (i.e., 1,224 +/- 230 cells/heart) at 35 days. Thus, even after direct
      intramyocardial injection, the total number of CSCs that remain in the murine
      heart is minimal (at 24 h, ~10 % of the cells injected; at 35 days, ~1 %). This
      new quantitative method of stem cell detection, which enables measurement of
      absolute cell number, should be useful to optimize cell-based therapies, not only
      for CSCs but also for other stem cells and other organs.

PMID- 23549980
TI  - EBV-related lymphomas: new approaches to treatment.
AB  - In the treatment of Epstein-Barr virus (EBV)-related lymphomas, there are few
      therapies specifically targeted against the latent virus within these tumors; in
      most cases the treatment approach is not different than the approach to EBV
      negative lymphomas. Nonetheless, current and emerging therapies focused on
      exploiting aspects of EBV biology may offer more targeted strategies for EBV
      positive lymphomas in the future. Conceptually, EBV-specific approaches include
      bolstering the antiviral/antitumor immune response with vaccines or EBV-specific
      cytotoxic T-lymphocytes, activating lytic viral genes to render the tumor cells
      susceptible to antiviral therapies, and inhibiting the downstream prosurvival or
      antiapoptotic pathways that may be activated by latent EBV proteins. EBV-specific
      cytotoxic T-cell infusions have proven effective in EBV-related
      posttransplantation lymphoproliferative disorder (EBV-PTLD) and expanding such
      adoptive immunotherapies to other EBV-related malignancies is an area of active
      research. However, other EBV-related lymphomas typically have more restricted,
      less immunogenic arrays of viral antigens to therapeutically target with adoptive
      immunotherapy compared with EBV-PTLD. Furthermore, the malignant EBV-positive
      tumor cells of Hodgkin lymphoma are scattered amid a dense infiltrate of
      regulatory T-cells, macrophages, and other cells that may dampen the antitumor
      efficacy of adoptive immunotherapy. Strategies to overcome these obstacles are
      areas of ongoing preclinical and clinical investigations. Some emerging
      approaches to EBV-related lymphomas include the coupling of agents that induce
      lytic viral replication with antiherpesvirus agents, or the use of small molecule
      inhibitors that block signaling pathways that are constitutively activated by
      EBV. EBV vaccines seem most promising for the treatment or prevention of EBV
      related malignancies, rather than the prevention of primary EBV infection. EBV
      vaccine trials in patients with residual or low-bulk EBV-related malignancies or
      for the prevention of EBV-PTLD in EBV-seronegative patients awaiting solid organ
      transplantation are ongoing.

PMID- 23549983
TI  - Retraction note: Reactive oxygen species and tumor metastasis. Mol. Cells 35
      (2013) 93-8.

PMID- 23549982
TI  - Topical calcineurin inhibitors for atopic dermatitis: review and treatment
      recommendations.
AB  - Atopic dermatitis (AD) is an inflammatory skin disease commonly affecting
      children and managed by pediatricians, primary care physicians, allergists, and
      dermatologists alike. For many years, the only available topical pharmacological
      treatment was topical corticosteroids. This changed in 2000-2001, when topical
      formulations of two calcineurin inhibitors (tacrolimus and pimecrolimus) were
      approved for short-term or chronic intermittent treatment of AD in patients >= 2
      years of age, in whom other treatments have been ineffective or contraindicated.
      These topical calcineurin inhibitors (TCIs) quickly became a popular treatment
      option due at least in part to concerns over adverse events associated with
      prolonged topical corticosteroid use, especially in children. However, based on
      theoretical concerns about a possible risk of lymphoma associated with TCI use, a
      Boxed Warning was placed on both products in 2006. Since then, despite an
      extensive body of evidence, no causal relationship has been demonstrated between
      TCI use and an increased risk of lymphoma; however, the US FDA has concluded that
      a link cannot be ruled out. In fact, based on post-marketing surveillance of
      spontaneous, literature, and solicited reports, we report here that the lymphoma
      incidence in the topical pimecrolimus-exposed population is up to approximately
      54-fold less than that seen in the general US population. This review summarizes
      the mechanism of action of TCIs, the factors that prompted the Boxed Warning, and
      recent TCI safety and efficacy data. Based on these data, both topical
      corticosteroids and TCIs should have defined roles in AD management, with TCIs
      favored for sensitive skin areas (e.g., face) and instances where topical
      corticosteroids have proven ineffective, thereby minimizing the risk of adverse
      effects with both drug classes.

PMID- 23549984
TI  - MicroRNA-148a can regulate runt-related transcription factor 3 gene expression
      via modulation of DNA methyltransferase 1 in gastric cancer.
AB  - Underexpression of the gene runt-related transcription factor 3 (RUNX3), an
      important tumor suppressor, is known to contribute to gastric cancer progression.
      However, the mechanism underlying aberrant RUNX3 expression has not been fully
      elucidated. We investigated the role of microRNA-148a (miR-148a) and DNA
      methyltransferases (DNMTs) in RUNX3 promoter methylation and gene expression.
      RUNX3 mRNA, RUNX3 protein, and methylation levels were assayed in human gastric
      cancer tissues and matched normal tissues, and AGS and BGC-823 cells by real-time
      reverse transcription PCR, Western blot, and methylation-specific PCR,
      respectively. A correlation between RUNX3 mRNA levels and that of miR-148a was
      also investigated in gastric cancer tissues. We found that RUNX3 mRNA levels were
      significantly downregulated in gastric cancer tissues compared with their matched
      normal tissues, and were closely associated with miR-148a expression. After
      treatment of human gastric cancer AGS and BGC-823 cells with the DNA methylation
      inhibitor 5-aza-2'-deoxycytidine, a significant increase in RUNX3 mRNA, RUNX3
      protein, and the non-methylated form of the RUNX3 promoter were observed relative
      to untreated cells. Enforced expression of miR-148a, which can modulate DNMT1 and
      DNMT3B, also increased the expression of RUNX3 in gastric cancer cells. Knockdown
      of DNMT1 was associated with increased levels of RUNX3 mRNA and RUNX3 protein,
      while knockdown of DNMT3B did not have any effect on these in BGC-823 cells. Our
      results show that miR-148a may regulate RUNX3 expression through modulation of
      DNMT1-dependent DNA methylation in gastric cancer and highlight a miRNA
      epigenetics regulation mechanism of gene expression.

PMID- 23549985
TI  - Effects of exogenous thiocyanate on mineral nutrients, antioxidative responses
      and free amino acids in rice seedlings.
AB  - The effects of exogenous thiocyanate (SCN(-)) on amino acids composition, content
      of mineral nutrients and antioxidative systems in plants were investigated. Young
      rice seedlings (Oryza sativa L. cv. XZX 45) were grown in nutrient solutions
      amended with potassium thiocyanate (KSCN). Activities of superoxide dismutase
      (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in plant
      materials were analyzed in vivo. Mineral nutrients and free amino acids in rice
      seedlings were also measured to determine metabolic responses to SCN(-) exposure.
      A significant reduction in transpiration and relative growth was recorded with
      all treatments (p < 0.05), while changes of total chlorophyll content in leaves
      was negligible (p > 0.05). SCN-induced toxicity appeared to be more sensitive to
      activities of POD in shoots and APX activities in roots than the others. The
      content of nutrient elements in rice seedlings exposed to exogenous SCN(-) was
      variable, while the effects were more evident at the highest SCN-treatment (p <
      0.05). Although the change of total free amino acids in shoots of SCN-exposed
      seedlings was negligible (p > 0.05), responses of different amino acids to SCN(-)
      application were quite different. Among fifteen free amino acids detected, serine
      (Ser), proline (Pro), and methionine (Met) increased, while asparagine (Asp)
      decreased with an increase of the doses of SCN(-) supplied. Phyto-transport of
      SCN(-) was apparent and the removal rates were positively correlated to the
      doses, suggesting that phyto-assimilation of SCN(-) is an enzymatic process
      through a potentially un-identified degradation pathway.

PMID- 23549986
TI  - Catecholaminergic polymorphic ventricular tachycardia and midventricular
      Takotsubo cardiomyopathy: a novel association?
AB  - Takotsubo cardiomyopathy (TTC) is a recently recognized clinical syndrome
      characterized by transient ventricular dysfunction in the absence of obstructive
      coronary artery disease. TTC primarily affects postmenopausal women; TTC in
      children and adolescents is only rarely reported. Furthermore, simultaneous
      occurrence of Takotsubo cardiomyopathy and primary electrical diseases has been
      previously reported in only four recent cases of female patients with congenital
      long QT syndrome. Here, we report the novel association of catecholaminergic
      polymorphic ventricular tachycardias and a midventricular type of TTC observed in
      a young female patient.

PMID- 23549987
TI  - [Surgical closure of the left atrial appendage in patients with atrial
      fibrillation. Indications, techniques and results].
AB  - Cardiac embolisation in patients with atrial fibrillation accounts for the most
      serious complication of cerebral infarction. The left atrial appendage resembles
      the origin of these cardiac emboli in the majority of cases, although other
      anatomical areas of the left atrium might also be prerequisites for thrombus
      formation. Surgical closure of the left atrial appendage during an ablation
      therapy incorporates the theoretical possibility of reducing the rate of cardiac
      cerebral infarction. In order to achieve closure, different surgical strategies
      exist: either exclusion by over-sewing or snaring or excision by using scissors
      or a stapling device. All therapies incorporate pros and cons. One of the major
      complications and most feared side-effect is the recanalisation of a formerly
      closed left atrial appendage, especially in a thrombus filled left atrial
      appendage cavity. But also reopening of the formerly closed orificium and still
      existing remnants with communication to the left atrium might stand for an
      increased risk. Due to the good results of left atrial appendage excision, this
      surgical therapy at the moment presents the surgical gold standard, as this
      therapy is recommended in the updated ESC guidelines for the management of atrial
      fibrillation. If excision of the left atrial appendage will reduce the risk of
      cardiac embolisation needs to be examined in large prospective-randomized trials
      with a controlled systemic follow-up. So far, excision of the left atrial
      appendage as an alternative to oral anticoagulation, especially in patients with
      atrial fibrillation, is not recommended.

PMID- 23549988
TI  - EHRA is all of us.

PMID- 23549989
TI  - [Surgical ablation of atrial fibrillation].

PMID- 23549990
TI  - A possible biomedical facility at the European Organization for Nuclear Research
      (CERN).
AB  - A well-attended meeting, called "Brainstorming discussion for a possible
      biomedical facility at CERN", was held by the European Organization for Nuclear
      Research (CERN) at the European Laboratory for Particle Physics on 25 June 2012.
      This was concerned with adapting an existing, but little used, 78-m circumference
      CERN synchrotron to deliver a wide range of ion species, preferably from protons
      to at least neon ions, with beam specifications that match existing clinical
      facilities. The potential extensive research portfolio discussed included beam
      ballistics in humanoid phantoms, advanced dosimetry, remote imaging techniques
      and technical developments in beam delivery, including gantry design. In
      addition, a modern laboratory for biomedical characterisation of these beams
      would allow important radiobiological studies, such as relative biological
      effectiveness, in a dedicated facility with standardisation of experimental
      conditions and biological end points. A control photon and electron beam would be
      required nearby for relative biological effectiveness comparisons. Research beam
      time availability would far exceed that at other facilities throughout the world.
      This would allow more rapid progress in several biomedical areas, such as in
      charged hadron therapy of cancer, radioisotope production and radioprotection.
      The ethos of CERN, in terms of open access, peer-reviewed projects and governance
      has been so successful for High Energy Physics that application of the same to
      biomedicine would attract high-quality research, with possible contributions from
      Europe and beyond, along with potential new funding streams.

PMID- 23549991
TI  - Candidate gene studies in hypodontia suggest role for FGF3.
AB  - INTRODUCTION: The majority of tooth agenesis cases are mild (hypodontia) and
      typically not associated with the gene mutations linked to oligodontia. From
      this, we hypothesise that most cases of tooth agenesis fit a polygenic mode of
      inheritance, where several genes with small effects cause a variety of varying
      phenotypes. MATERIALS AND METHODS: In this study, we looked at 18 not typically
      studied genes in this condition, to ascertain their contribution to hypodontia.
      Our study subjects consisted of 167 patients with hypodontia and their parents
      from two cohorts (one from Brazil and one from Turkey). An additional 465 DNA
      samples (93 cases with hypodontia and 372 controls without family history for
      tooth agenesis or oral clefts) from Brazil were also available for this study.
      Ninety-three single nucleotide polymorphisms that maximally represent the linkage
      disequilibrium structure of the genes for the 18 genes were selected and
      genotyped using Taqman chemistry. Chi square was used to test if genotype
      distributions were in Hardy-Weinberg equilibrium, and 24 markers that were in
      Hardy-Weinberg equilibrium and had allele frequencies higher than 5 % in a panel
      of 50 CEPH samples were further tested. Association between hypodontia and
      genetic variants was tested with the transmission disequilibrium test within the
      programme Family-Based Association Test (FBAT) and by using Chi square and
      Fisher's exact tests. Alpha at a level of 0.05 was used to report results.
      RESULTS: Results suggest possible associations between several genes and
      hypodontia in the three populations. In the Turkish cohort (n = 51 parent
      affected child trios) the most significant results were as follows: FGF3
      rs1893047, p = 0.08; GLI3 rs929387, p = 0.03; GLI3 haplotype rs929387-rs846266, p
      = 0.002; and PAX9 rs2073242, p = 0.03. In the Brazilian cohort (n = 116 parent
      affected child trios), the results were as follows: DLX1 rs788173, p = 0.07; FGF3
      rs12574452, p = 0.03; GLI2 rs1992901, p = 0.03; and PITX2 rs2595110, p = 0.01.
      The second Brazilian cohort also suggested that FGF3 (rs12574452, p = 0.01) is
      associated with hypodontia and added EDAR (rs17269487, p = 0.04), LHX6 (rs989798,
      p = 0.02), and MSX1 (rs12532, p = 0.003). CONCLUSION: Our results suggest that
      several genes are potentially associated with hypodontia and their individual
      contributions may be modest. Hence, these cases may not be explained by
      inactivating mutations such as many oligodontia cases segregating in a Mendelian
      fashion but rather are influenced by one or more susceptibility alleles in
      multiple small effect genes.

PMID- 23549992
TI  - Comment on methodological problems in Hansson et al.: Oral microflora and dietary
      intake in infants with congenital heart disease: a case control study.

PMID- 23549993
TI  - Clinical, radiographic and histologic analysis of the effects of pulp capping
      materials used in pulpotomies of human primary teeth.
AB  - AIM: To compare the clinical, radiographic and histological responses of the pulp
      to mineral trioxide aggregate (MTA), calcium hydroxide (CH) and Portland cement
      (PC) when used as a pulpotomy agent in human primary teeth. STUDY DESIGN: Forty
      five mandibular primary molar teeth were randomly assigned to CH, MTA or PC
      groups and treated by pulpotomy technique. METHODS: The teeth were treated by
      conventional pulpotomy technique, differing only in the capping material for each
      group. Clinical and radiographic evaluations were recorded at 6-, 12- and 24
      month follow-up. Teeth in the regular exfoliation period were further processed
      for histologic analysis. STATISTICS: Data were tested using parametric tests at a
      significance level of 5 %. The histological results were expressed descriptively.
      RESULTS: Clinically and radiographically, the MTA and PC groups showed 100 %
      success rates at 6, 12 and 24 months. In CH group, several teeth presented
      clinical and radiographic failures detected throughout the follow-up period, and
      internal resorption was a frequent radiographic finding. Histologic analysis
      revealed the presence of dentine-like mineralised material deposition
      obliterating the root canal in the PC and MTA groups. CH group presented, in most
      of the sections, necrotic areas in the root canals. CONCLUSIONS: MTA and PC may
      serve as effective materials for pulpotomies of primary teeth as compared to CH.
      Although our results are very encouraging, further studies and longer follow-up
      assessments are needed in order to determine the safe clinical indication of
      Portland cement.

PMID- 23549994
TI  - Caries experience in primary teeth of four birth cohorts: a practice-based study.
AB  - AIM: To investigate the survival of caries-free primary teeth in four age cohorts
      in the city of Kemi, Finland, as well as association of survival of primary teeth
      among boys and girls and among high and low caries risk individuals. STUDY
      DESIGN: This was a practice-based follow-up study based on dental records.
      METHODS: The data were collected from the electronic oral health patient records
      of the municipal health centre of the city of Kemi, covering four different birth
      cohorts (1985, 1990, 1995 and 2000). The total number of children was 4,488.
      STATISTICS: Kaplan-Meier curves were drawn to illustrate the survival of caries
      free primary molars . Statistical difference between the groups was analysed
      using the log-rank test and Cox proportional hazards regression analysis. The
      retrospective caries risk definition for individuals was based on the early
      restorations in the first permanent molars. RESULTS: In the earlier cohorts,
      primary molars survived caries-free for a shorter period than in the later
      cohorts (p < 0.001). However, in the 2000 cohort, the survival curve, having
      shown at the beginning only some caries incidence, bended strongly downwards at
      the age of 8 years. The survival time of the primary molars remaining caries-free
      was shorter for those with high caries risk (p < 0.001) as well for boys compared
      with girls in all cohorts (p = 0.001). CONCLUSION: The course of the survival
      curve of the 2000 age cohort indicates a halt in the improvement of dental caries
      prevalence, but the follow-up period was too short to allow monitoring the
      progress further. Continuing oral health promotion to all children, and
      particularly risk individuals must be emphasised.

PMID- 23549995
TI  - A comparative study of clinical effectiveness of fissure sealing with and without
      bonding systems: 3-year results.
AB  - AIM: This prospective clinical study evaluated the sealant retention rate and
      caries-preventive efficacy of two fissure sealing techniques over a 3-year
      period. METHODS: Subjects (87) aged between 6.5 and 11.5 years were enrolled into
      two groups. In Group I (41 subjects), a resin-based fissure sealant (Fissurit FX,
      VOCO, Germany) was placed on all four sound permanent first molars (FPM-164
      teeth) of each subject and in Group II (46 subjects) on 4 caries-free premolars
      (P1-2 182 teeth),using the following adhesives systems: Optibond FL (Kerr, USA),
      Optibond Solo plus (Kerr, USA), Prompt-L-Pop (3 M ESPE, USA) or the conventional
      acid-etch technique. Sealed teeth were evaluated at baseline, 6, 12, 18, 24 and
      36-month intervals with regard to retention and new caries development. Sealant
      retention was scored as: (1) complete retention; (2) partial loss; (3) complete
      loss of sealant. STATISTICS: Wilcoxon-signed rank test was used to analyse the
      data. RESULTS: The complete retention rate was: Optibond FL/sealant 80.01-82.92
      %, Optibond Solo plus/sealant 73.78-74.27 %, Prompt-L-Pop/sealant 42.84-53.65 %
      versus acid-etch technique 62.86-71.44 % on FPM and P1-2 (p < 0.05). The fissure
      caries incidence rate was: Optibond FL/sealant 2.43-2.85 %, Optibond Solo
      plus/sealant 2.85-4.76 %, Prompt-L-Pop/sealant 24.40-34.28 % versus acid-etch
      technique 16.66-17.14 % (p < 0.05) on FPM and P1-2. A statistically significant
      difference in sealant retention rate was observed between FPM and P1-2, using the
      self-etching adhesive system Prompt-L-Pop and acid-etch technique. CONCLUSION: It
      may be concluded that the use of adhesive systems Optibond FL and Optibond Solo
      plus yielded better fissure sealing performance.

PMID- 23549996
TI  - Oral microflora and dietary intake in infants with congenital heart disease: a
      case-control study : Authors' response to comment by Booth.

PMID- 23549998
TI  - Physiologic and hematologic concerns of rotary blood pumps: what needs to be
      improved?
AB  - Over the past few decades, advances in ventricular assist device (VAD) technology
      have provided a promising therapeutic strategy to treat heart failure patients.
      Despite the improved performance and encouraging clinical outcomes of the new
      generation of VADs based on rotary blood pumps (RBPs), their physiologic and
      hematologic effects are controversial. Currently, clinically available RBPs run
      at constant speed, which results in limited control over cardiac workload and
      introduces blood flow with reduced pulsatility into the circulation. In this
      review, we first provide an update on the new challenges of mechanical
      circulatory support using rotary pumps including blood trauma, increased non
      surgical bleeding rate, limited cardiac unloading, vascular malformations, end
      organ function, and aortic valve insufficiency. Since the non-physiologic flow
      characteristic of these devices is one of the main subjects of scientific debate
      in the literature, we next emphasize the latest research regarding the
      development of a pulsatile RBP. Finally, we offer an outlook for future research
      in the field. 

PMID- 23549999
TI  - Kisspeptin: past, present, and prologue.
AB  - Research in the nineteenth and early twentieth century established that the brain
      awakens reproduction, governs reproductive activity in the adult of virtually all
      vertebrates. By 1950, nearly 100 years later, scientists realized that the
      hypothalamus and its neurosecretory products play a key role in regulating
      gonadal function in both males and females. Another 20 years would be required to
      reveal the chemical identity of GnRH and establish that neurons producing GnRH
      represent the final common pathway through which the brain regulates gonadotropin
      secretion. It had also become clear that GnRH neurons behave more like motor
      neurons-better perhaps at going than stopping-and are themselves regulated by a
      complex network of afferent inputs, which guide the tempo of sexual maturation,
      regulate estrous and menstrual cycles, control seasonal breeding, and stop
      reproduction under adversity. In 2003, the revelation that kisspeptin and its
      receptor are critical for reproduction opened a floodgate of research documenting
      the role of kisspeptin neurons as central processors of reproduction. Today,
      there is wide consensus that kisspeptin signaling in the brain is essential,
      providing the impetus to GnRH neurons to awaken at puberty and reigning the
      activity of these neurons when discretion is advised. We celebrate this watershed
      moment-with full knowledge that time and discovery will provide context and
      perspective to even these heady days.

PMID- 23549997
TI  - Night/day ratios of ambulatory blood pressure among healthy adolescents: roles of
      race, socioeconomic status, and psychosocial factors.
AB  - BACKGROUND: Elevated nighttime blood pressure (BP) predicts hypertension and its
      complications in adulthood. PURPOSE: This study aimed to assess the independent
      effects of race and family income on night/day BP among adolescents and to
      examine whether negative emotions, low positive resources, and unpleasant
      interactions during the day are also related. METHODS: Healthy African American
      and Caucasian high school students (N = 239) wore an ambulatory BP monitor for 48
      h, recorded quality of ongoing interpersonal interactions, and completed
      questionnaires. RESULTS: African Americans and those with lower family income had
      higher night/day BP ratios. African Americans reporting greater negative
      emotions, lower positive resources, and more unpleasant interactions had higher
      night/day BP ratios. CONCLUSIONS: Racial differences in night BP emerge by
      adolescence, independent of family income. African Americans, especially those
      high in negative emotions and low in positive resources, may be at higher
      relative risk for hypertension later in life in part due to elevated night BP.

PMID- 23550000
TI  - Structure, synthesis, and phylogeny of kisspeptin and its receptor.
AB  - The kisspeptin system is considered to be essential for successful mammalian
      reproduction. In addition to the Kiss1 peptide, Kiss2, the product of kiss2 (the
      kiss1 paralogue), has also been shown to activate kisspeptin receptor signaling
      pathways in nonmammalian species. Furthermore, in nonmammalian species, there are
      two subtypes of receptors, Gpr54-1 (known as GPR54 or Kiss1R in mammals) and
      Gpr54-2. Although complete understanding of the two kisspeptin-two kisspeptin
      receptor systems in vertebrates is not so simple, a careful examination of the
      phylogeny of their genes may provide insights into the functional generality and
      differences among the kisspeptin systems in different animal phyla. In this
      chapter, we first discuss the structure of kisspeptin ligands, Kiss1 and Kiss2,
      and their characteristics as physiologically active peptides. Then, we discuss
      the evolutionary traits of kiss1 and kiss2 genes and their receptor genes, gpr54
      1 and gpr54-2. It appears that each animal species has selected either kiss1 or
      kiss2 rather randomly, leading us to propose that some of the important
      characteristics of kisspeptin neurons, such as steroid sensitivity and the
      anatomical relationship with the hypophysiotropic GnRH1 neurons, may be the keys
      to understanding the general functions of different kisspeptin neuronal
      populations throughout vertebrates. Species differences in kiss1/kiss2 may also
      provide insights into the evolutionary mechanisms of paralogous gene-expressing
      neuronal systems. Finally, because kisspeptins belong to one of the members of
      the RFamide peptide families, we discuss the functional divergence of kisspeptins
      from the other RFamide peptides, which may be explained from phylogenetic
      viewpoints.

PMID- 23550002
TI  - The effects of kisspeptin on gonadotropin release in non-human mammals.
AB  - The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which is cleaved
      into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter reviews in
      detail the effects of kisspeptin on gonadotropin secretion in non-human mammals.
      Studies of kisspeptin's effects have included both acute and chronic
      administration regimens via a number of administration routes. Acute kisspeptin
      stimulates gonadotropin secretion in a wide range of species of non-human
      mammals, including rats, mice, hamsters, sheep, pigs, goats, cows, horses, and
      monkeys. In general, the stimulatory effect of kisspeptin treatment is more
      pronounced for LH than FSH secretion. Kisspeptin is thought to exert its
      stimulatory effects on LH and FSH release via stimulation of GnRH release from
      the hypothalamus, since pre--administration of a GnRH antagonist prevents
      kisspeptin's stimulation of gonadotropin secretion. Although the kisspeptin
      receptor is also expressed on anterior pituitary cells of some species, and
      incubation of anterior pituitary cells with high concentrations of kisspeptin can
      stimulate in vitro LH release, the contribution of direct effects of kisspeptin
      on the pituitary is thought to be negligible in vivo. Continuous kisspeptin
      administration results in reduced sensitivity to the effects of kisspeptin, in
      some species. This desensitization is thought to occur at the level of the
      kisspeptin receptor, since the response of the pituitary gland to exogenous GnRH
      is maintained. Overall, the findings discussed in this chapter are invaluable to
      the understanding of the reproductive role of kisspeptin and the potential
      therapeutic uses of kisspeptin for the treatment of fertility disorders.

PMID- 23550001
TI  - Neuroanatomy of the kisspeptin signaling system in mammals: comparative and
      developmental aspects.
AB  - Our understanding of kisspeptin and its actions depends, in part, on a detailed
      knowledge of the neuroanatomy of the kisspeptin signaling system in the brain. In
      this chapter, we will review our current knowledge of the distribution of
      kisspeptin cells, fibers, and receptors in the mammalian brain, including the
      development, phenotype, and projections of different kisspeptin subpopulations. A
      fairly consistent picture emerges from this analysis. There are two major groups
      of kisspeptin cell bodies: a large number in the arcuate nucleus (ARC) and a
      smaller collection in the rostral periventricular area of the third ventricle
      (RP3V) of rodents and preoptic area (POA) of non-rodents. Both sets of neurons
      project to GnRH cell bodies, which contain Kiss1r, and the ARC kisspeptin
      population also projects to GnRH axons in the median eminence. ARC kisspeptin
      neurons contain neurokinin B and dynorphin, while a variable percentage of those
      cells in the RP3V of rodents contain galanin and/or dopamine. Neurokinin B and
      dynorphin have been postulated to contribute to the control of GnRH pulses and
      sex steroid negative feedback, while the role of galanin and dopamine in rostral
      kisspeptin neurons is not entirely clear. Kisspeptin neurons, fibers, and Kiss1r
      are found in other areas, including widespread areas outside the hypothalamus,
      but their physiological role(s) in these regions remains to be determined.

PMID- 23550003
TI  - Effects of kisspeptin on hormone secretion in humans.
AB  - Studies of the actions of kisspeptin in human subjects have examined the effects
      of different kisspeptin isoforms, doses, and routes of administration on LH
      secretion, a surrogate measure of GnRH release. These studies, in addition to
      detailing how these different variables affect LH secretion in response to
      kisspeptin, have produced new insights into kisspeptin physiology: (1) Brief
      exposure to kisspeptin results in sustained GnRH release lasting ~17 min in men.
      (2) Women in different phases of the menstrual cycle have differences in their
      response to kisspeptin, suggesting that endogenous kisspeptin secretion and GnRH
      neuronal responsiveness vary in response to the changing sex-steroid environment
      across the menstrual cycle. (3) Kisspeptin resets the GnRH pulse generator in
      men, but does not appear to do so in women. (4) Continuous exposure to kisspeptin
      results in desensitization to kisspeptin, and thus kisspeptin has the potential
      to either stimulate or suppress reproductive endocrine activity depending on the
      mode of administration. These findings pave the way for future studies using
      kisspeptin as a physiologic, diagnostic, and therapeutic tool in both healthy
      adults and in patients with reproductive disorders.

PMID- 23550005
TI  - Molecular biology of the kisspeptin receptor: signaling, function, and mutations.
AB  - Kisspeptin receptor (KISS1R) signaling is essential for the hallmark increase in
      pulsatile GnRH secretion characteristic of the onset of puberty in humans and
      experimental animals. Loss-of-function mutations in KISS1R are associated with
      idiopathic hypogonadotropic hypogonadism in humans. Also, mutations with
      confirmed association with idiopathic central precocious puberty were identified
      in kisspeptin and KISS1R. These observations underscore the role of KISS1R
      signaling for normal pubertal development. Moreover, investigation of the
      mechanisms underlying the gain-of-function mutation in KISS1R indicates that the
      duration of KISS1R signaling is critical for the role of this receptor in timing
      the onset of puberty in humans. These findings further endorse the need to
      uncover the mechanisms, as well as yet-unknown proteins, involved in each step of
      KISS1R signaling. This knowledge is expected to advance our understanding of
      normal and abnormal pubertal development, as well as to help uncover the role of
      KISS1R signaling in non-hypothalamic tissues such as the placenta. This chapter
      discusses recent advances in the investigation of KISS1R signaling and function,
      as well as potential pathophysiological implications of naturally occurring
      mutations in this receptor identified in humans with reproductive disorders.

PMID- 23550006
TI  - Kisspeptin antagonists.
AB  - Kisspeptin is now known to be an important regulator of the hypothalamic-
      pituitary-gonadal axis and is the target of a range of regulators, such as
      steroid hormone feedback, nutritional and metabolic regulation. Kisspeptin binds
      to its cognate receptor, KISS1R (also called GPR54), on GnRH neurons and
      stimulates their activity, which in turn provides an obligatory signal for GnRH
      secretion-thus gating down-stream events supporting reproduction. The development
      of peripherally active kisspeptin antagonists could offer a unique therapeutic
      agent for treating hormone-dependent disorders of reproduction, including
      precocious puberty, endometriosis, and metastatic prostate cancer. The following
      chapter discusses the advances made in the search for both peptide and small
      molecule kisspeptin antagonists and their use in delineating the role of
      kisspeptin within the reproductive system. To date, four peptide antagonists and
      one small molecule antagonist have been designed.

PMID- 23550007
TI  - Kisspeptin and clinical disorders.
AB  - The hypothalamic hormone GnRH has traditionally been viewed as a central driver
      of the hypothalamic-pituitary-gonadal axis. Pulsatile GnRH release is required
      for pulsatile gonadotropin secretion, which then modulates gonadal steroid
      feedback and brings about full fertility in the adult. Pathways governing GnRH
      ontogeny and physiology have been discovered by studying humans with disorders of
      GnRH secretion. In this chapter, the human genetics of the kisspeptin signaling
      pathway in patients with diverse reproductive phenotypes will be explored. The
      discovery of defects in the kisspeptin system in several reproductive disorders
      has shed light on the mechanisms involved in regulating GnRH secretion, revealing
      the critical role played by the kisspeptin signaling pathway in pubertal
      initiation and reproductive function.

PMID- 23550004
TI  - Kisspeptin excitation of GnRH neurons.
AB  - Kisspeptin binding to its cognate G protein-coupled receptor (GPR54, aka Kiss1R)
      in gonadotropin-releasing hormone (GnRH) neurons stimulates peptide release and
      activation of the reproductive axis in mammals. Kisspeptin has pronounced pre-
      and postsynaptic effects, with the latter dominating the excitability of GnRH
      neurons. Presynaptically, kisspeptin increases the excitatory drive (both GABA-A
      and glutamate) to GnRH neurons and postsynaptically, kisspeptin inhibits an A
      type and inwardly rectifying K(+) (Kir 6.2 and GIRK) currents and activates
      nonselective cation (TRPC) currents to cause long-lasting depolarization and
      increased action potential firing. The signaling cascades and the multiple
      intracellular targets of kisspeptin actions in native GnRH neurons are continuing
      to be elucidated. This review summarizes our current state of knowledge about
      kisspeptin signaling in GnRH neurons.

PMID- 23550008
TI  - Beyond the GnRH axis: kisspeptin regulation of the oxytocin system in pregnancy
      and lactation.
AB  - Circulating oxytocin is critical for normal birth and lactation. Oxytocin is
      synthesised by hypothalamic supraoptic and paraventricular neurons and is
      released from the posterior pituitary gland into the circulation. Oxytocin
      secretion depends on action potentials initiated at the cell body, and we have
      shown that intravenous (IV) administration of kisspeptin-10 transiently increases
      the firing rate of supraoptic nucleus oxytocin neurons in anaesthetised, non
      pregnant, pregnant and lactating rats. This peripheral effect is likely via vagal
      afferent input, because disruption of vagal afferents prevented the excitation.
      In our initial studies, intracerebroventricular (icv) administration of
      kisspeptin-10 did not alter the firing rate of oxytocin neurons in non-pregnant
      rats. Remarkably, we have now gathered unpublished observations showing that icv
      kisspeptin-10 transiently excites oxytocin neurons in late pregnancy and during
      lactation, suggesting that a central kisspeptin excitation of oxytocin neurons
      emerges at the end of pregnancy, when increased oxytocin secretion is required
      for delivery of the fetus and for milk let-down after delivery.

PMID- 23550011
TI  - Sex steroid regulation of kisspeptin circuits.
AB  - Kisspeptin cells appear to be the "missing link," bridging the divide between
      levels of gonadal steroids and feedback control of gonadotropin-releasing hormone
      (GnRH) secretion. Kisspeptin neurons are important in the generation of both sex
      steroid negative and estrogen positive feedback signals to GnRH neurons, the
      former being involved in the tonic regulation of GnRH secretion in males and
      females and the latter governing the preovulatory GnRH/luteinizing hormone (LH)
      surge in females. In rodents, kisspeptin-producing cells populate the
      anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), and
      estrogen regulation of kisspeptin has been extensively studied in these regions.
      Kisspeptin cells in the ARC appear to receive and forward signals applicable to
      negative feedback regulation of GnRH. In the female rodent AVPV, kisspeptin cells
      are important for positive feedback regulation of GnRH and the preovulatory LH
      surge. In sheep and primates, a rostral population of kisspeptin cells is located
      in the dorsolateral preoptic area (POA) as well as the ARC. Initial studies
      showed kisspeptin cells in the latter were involved in both the positive and
      negative feedback regulation of GnRH. Interestingly, further studies now suggest
      that kisspeptin cells in the ovine POA may also play an important role in
      generating estrogen positive feedback. This chapter discusses the current
      consensus knowledge regarding the interaction between sex steroids and kisspeptin
      neurons in mammals.

PMID- 23550009
TI  - The development of kisspeptin circuits in the Mammalian brain.
AB  - The neuropeptide kisspeptin, encoded by the Kiss1 gene, is required for mammalian
      puberty and fertility. Examining the development of the kisspeptin system
      contributes to our understanding of pubertal progression and adult reproduction
      and sheds light on possible mechanisms underlying the development of reproductive
      disorders, such as precocious puberty or hypogonadotropic hypogonadism. Recent
      work, primarily in rodent models, has begun to study the development of
      kisspeptin neurons and their regulation by sex steroids and other factors at
      early life stages. In the brain, kisspeptin is predominantly expressed in two
      areas of the hypothalamus, the anteroventral periventricular nucleus and
      neighboring periventricular nucleus (pre-optic area in some species) and the
      arcuate nucleus. Kisspeptin neurons in these two hypothalamic regions are
      differentially regulated by testosterone and estradiol, both in development and
      in adulthood, and also display differences in their degree of sexual dimorphism.
      In this chapter, we discuss what is currently known and not known about the
      ontogeny, maturation, and sexual differentiation of kisspeptin neurons, as well
      as their regulation by sex steroids and other factors during development.

PMID- 23550010
TI  - Kisspeptin and puberty in mammals.
AB  - Since the discovery of the G-protein coupled receptor 54 (kisspeptin receptor)
      and its ligand, kisspeptin, our understanding of the neurobiological mechanisms
      that govern the pituitary-gonadal axis has evolved dramatically. In this chapter,
      we have reviewed progress regarding the relationship between kisspeptin and
      puberty, and have proposed a novel hypothesis for the role of kisspeptin
      signaling in the onset of this crucial developmental event. According to this
      hypothesis, although kisspeptin neurons in the arcuate nucleus (ARC) are critical
      for puberty, this is simply because these cells are an integral component of the
      hypothalamic GnRH pulse generating mechanism that drives intermittent release of
      the decapeptide, as an increase in GnRH is obligatory for the onset of puberty.
      In our model, ARC kisspeptin neurons play no "regulatory" role in controlling the
      timing of puberty. Rather, as a component of the neural network responsible for
      GnRH pulse generation, they subserve upstream regulatory mechanisms that are
      responsible for the timing of puberty.

PMID- 23550012
TI  - Kisspeptin and GnRH pulse generation.
AB  - The reproductive neuropeptide gonadotropin-releasing hormone (GnRH) has two modes
      of secretion. Besides the surge mode, which induces ovulation in females, the
      pulse mode of GnRH release is essential to cause various reproductive events in
      both sexes, such as spermatogenesis, follicular development, and sex steroid
      synthesis. Some environmental cues control gonadal activities through modulating
      GnRH pulse frequency. Researchers have looked for the anatomical location of the
      mechanism generating GnRH pulses, the GnRH pulse generator, in the brain, because
      an artificial manipulation of GnRH pulse frequency is of therapeutic importance
      to stimulate or suppress gonadal activity. Discoveries of kisspeptin and,
      consequently, KNDy (kisspeptin/neurokinin B/dynorphin) neurons in the
      hypothalamus have provided a clue to the possible location of the GnRH pulse
      generator. Our analyses of hypothalamic multiple-unit activity revealed that KNDy
      neurons located in the hypothalamic arcuate nucleus might play a central role in
      the generation of GnRH pulses in goats, and perhaps other mammalian species. This
      chapter further discusses the possible mechanisms for GnRH pulse generation.

PMID- 23550014
TI  - Electrophysiology of kisspeptin neurons.
AB  - Kisspeptin is an important regulator of reproduction. Electrophysiological
      studies show that kisspeptin neurons of the arcuate nucleus that co-localize
      neurokinin B and dynorphin (aka KNDy neurons) fire action potentials in a tonic,
      irregular, or burst firing manner. Gonadectomy dramatically alters the membrane
      properties of KNDY neurons from male mice and induces somatic hypertrophy. NMDA,
      leptin, and neurokinin B are potent activators of KNDY neuron electrical activity
      and GABA inhibits KNDY neurons. The firing pattern of kisspeptin neurons located
      in the RP3V fluctuates with the estrus cycle and is strongly modulated by
      glutamate and GABA. Thus, kisspeptin neurons are capable of burst firing, and
      their activity is modulated by sex steroids and other regulatory factors.

PMID- 23550015
TI  - Metabolic regulation of kisspeptin.
AB  - Body energy balance and metabolic signals are important modulators of puberty and
      reproductive function, so that perturbations of metabolism and energy reserves
      (ranging from persistent energy insufficiency to morbid obesity) are frequently
      linked to reproductive disorders. The mechanisms for the tight association
      between body metabolic state and reproduction are multifaceted, and likely
      involve numerous peripheral hormones and central transmitters. In recent years, a
      prominent role of kisspeptins in the central pathways responsible for conveying
      metabolic information into the brain centers responsible for reproductive
      control, and specifically GnRH neurons, has been proposed on the basis of a
      wealth of expression and functional data. In this chapter, we will summarize such
      evidence, with special attention to the potential (direct and/or indirect)
      interaction of leptin and kisspeptin pathways. In addition, other potential
      metabolic modulators of kisspeptin signaling, as well as some of the putative
      molecular mechanisms for the metabolic regulation of Kiss1 will be briefly
      reviewed. Conflictive data, including those questioning an essential role of
      Kiss1 neurons in mediating leptin effects on the reproductive axis, will be also
      discussed. All in all, we aim to provide an integral and balanced view of the
      physiological relevance and potential mechanisms for the metabolic control of the
      kisspeptin system, as important pathway for the integral regulation of energy
      balance, puberty onset, and fertility.

PMID- 23550013
TI  - Interactions between kisspeptins and neurokinin B.
AB  - Reproductive function is tightly regulated by an intricate network of central and
      peripheral factors; however, the precise mechanism triggering critical
      reproductive events, such as puberty onset, remains largely unknown. Recently,
      the neuropeptides kisspeptin (encoded by Kiss1) and neurokinin B (NKB, encoded by
      TAC3 in humans and Tac2 in rodents) have been placed as essential gatekeepers of
      puberty. Studies in humans and rodents have revealed that loss-of-function
      mutations in the genes encoding either kisspeptin and NKB or their receptors,
      Kiss1r and neurokinin 3 receptor (NK3R), lead to impaired sexual maturation and
      infertility. Kisspeptin, NKB, and dynorphin A are co-expressed in neurons of the
      arcuate nucleus (ARC), so-called Kisspeptin/NKB/Dyn (KNDy) neurons. Importantly,
      these neurons also co-express NK3R. Compelling evidence suggests a stimulatory
      role of NKB (or the NK3R agonist, senktide) on LH release in a number of species.
      This effect is likely mediated by autosynaptic inputs of NKB on KNDy neurons to
      induce the secretion of gonadotropin-releasing hormone (GnRH) in a kisspeptin-
      dependent manner, with the coordinated actions of other neuroendocrine factors,
      such as dynorphin, glutamate, or GABA. Thus, we have proposed a model in which
      NKB feeds back to the KNDy neuron to shape the pulsatile release of kisspeptin,
      and hence GnRH, in a mechanism also dependent on the sex steroid level.
      Additionally, NKB may contribute to the regulation of the reproductive function
      by metabolic cues. Investigating how NKB and kisspeptin interact to regulate the
      gonadotropic axis will offer new insights into the control of GnRH release during
      puberty onset and the maintenance of the reproductive function in adulthood,
      offering a platform for the understanding and treatment of a number of
      reproductive disorders.

PMID- 23550017
TI  - Kisspeptin and seasonality of reproduction.
AB  - Wild and domesticated species display seasonality in reproductive function,
      controlled predominantly by photoperiod. Seasonal alterations in breeding status
      are caused by changes in the secretion of gonadotropin-releasing hormone (GnRH)
      that are mediated by upstream neuronal afferents that regulate the GnRH cells. In
      particular, kisspeptin appears to play a major role in seasonality of
      reproduction, transducing the feedback effect of gonadal steroids as well as
      having an independent (nonsteroid dependent) circannual rhythm. A substantial
      body of data on this issue has been obtained from studies in sheep and hamsters
      and this is reviewed here in detail. Kisspeptin function is upregulated during
      the breeding season in sheep, stimulating reproductive function, but
      contradictory data are found in Siberian and Syrian hamsters. The relative
      quiescence of kisspeptin cells in the nonbreeding season can be counteracted by
      administration of the peptide, leading to activation of reproductive function.
      Although there is a major role for melatonin in the transduction of photoperiod
      to the reproductive system, kisspeptin cells do not appear to express the
      melatonin receptor, so the means by which seasonality changes the level of
      kisspeptin activity remains unknown.

PMID- 23550018
TI  - Stress regulation of kisspeptin in the modulation of reproductive function.
AB  - Stressful stimuli abound in modern society and have shaped evolution through
      altering reproductive development, behavior, and physiology. The recent
      identification of kisspeptin as an important component of the hypothalamic
      regulatory circuits involved in reproductive homeostasis sparked a great deal of
      research interest that subsequently implicated kisspeptin signaling in the relay
      of metabolic, environmental, and physiological cues to the hypothalamo-pituitary
      gonadal axis. However, although it is widely recognized that exposure to stress
      profoundly impacts on reproductive function, the roles of kisspeptin within the
      complex mechanisms underlying stress regulation of reproduction remain poorly
      understood. We and others have recently demonstrated that a variety of
      experimental stress paradigms downregulate the expression of kisspeptin ligand
      and receptor within the reproductive brain. Coincidently, these stressors also
      inhibit gonadotropin secretion and delay pubertal onset-processes that rely on
      kisspeptin signaling. However, a modest literature is inconsistent with an
      exclusively suppressive influence of stress on the reproductive axis and suggests
      that complicated neural interactions and signaling mechanisms translate the
      stress response into reproductive perturbations. The purpose of this chapter is
      to review the evidence for a novel role of kisspeptin signaling in the modulation
      of reproductive function by stress and to broaden the understanding of this
      timely phenomenon.

PMID- 23550016
TI  - Circadian regulation of kisspeptin in female reproductive functioning.
AB  - Female reproductive functioning requires the precise temporal -organization of
      numerous neuroendocrine events by a master circadian brain clock located in the
      suprachiasmatic nucleus. Across species, including humans, disruptions to
      circadian timing result in pronounced deficits in ovulation and fecundity. The
      present chapter provides an overview of the circadian control of female
      reproduction, underscoring the significance of kisspeptin as a key locus of
      integration for circadian and steroidal signaling necessary for the initiation of
      ovulation.

PMID- 23550019
TI  - Effects of environmental endocrine disruptors and phytoestrogens on the
      kisspeptin system.
AB  - Sex steroid hormones, most notably estradiol, play a pivotal role in the sex
      specific organization and function of the kisspeptin system. Endocrine-
      disrupting compounds are anthropogenic or naturally occurring compounds that
      interact with steroid hormone signaling. Thus, these compounds have the potential
      to disrupt the sexually dimorphic ontogeny and function of kisspeptin signaling
      pathways, resulting in adverse effects on neuroendocrine physiology. This chapter
      reviews the small but growing body of evidence for endocrine disruption of the
      kisspeptin system by the exogenous estrogenic compounds bisphenol A,
      polychlorinated biphenyl mixtures, and the phytoestrogen genistein. Disruption is
      region, sex, and compound specific, and associated with shifts in the timing of
      pubertal onset, irregular estrous cycles, and altered sociosexual behavior. These
      effects highlight that disruption of kisspeptin signaling pathways could have
      wide ranging effects across multiple organ systems, and potentially underlies a
      suite of adverse human health trends including precocious female puberty,
      idiopathic infertility, and metabolic syndrome.

PMID- 23550020
TI  - Model systems for studying kisspeptin signalling: mice and cells.
AB  - Kisspeptins are a family of overlapping neuropeptides, encoded by the Kiss1 gene,
      that are required for activation and maintenance of the mammalian reproductive
      axis. Kisspeptins act within the hypothalamus to stimulate release of
      gonadotrophic releasing hormone and activation of the pituitary-gonadal axis.
      Robust model systems are required to dissect the regulatory mechanisms that
      control Kiss1 neuronal activity and to examine the molecular consequences of
      kisspeptin signalling. While studies in normal animals have been important in
      this, transgenic mice with targeted mutations affecting the kisspeptin signalling
      pathway have played a significant role in extending our understanding of
      kisspeptin physiology. Knock-out mice recapitulate the reproductive defects
      associated with mutations in humans and provide an experimentally tractable model
      system to interrogate regulatory feedback mechanisms. In addition, transgenic
      mice with cell-specific expression of modulator proteins such as the CRE
      recombinase or fluorescent reporter proteins such as GFP allow more sophisticated
      analyses such as cell or gene ablation or electrophysiological profiling. At a
      less complex level, immortalized cell lines have been useful for studying the
      role of kisspeptin in cell migration and metastasis and examining the
      intracellular signalling events associated with kisspeptin signalling.

PMID- 23550021
TI  - Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal
      pathways.
AB  - Icaritin, a hydrolytic product of icaritin, is isolated from the traditional
      Chinese medicinal herb epimedium. Icaritin inhibits the proliferation of several
      tumor cell lines, but its effect on acute myeloid leukemia (AML) and underlying
      mechanisms remain to be identified. In the present study, we demonstrated that
      icaritin inhibits the proliferation of human AML cell lines NB4, HL60, and U937,
      in a dose- and time-dependent manner. Importantly, icaritin showed anti-leukemia
      activity on bone marrow mononuclear cells from 15 newly diagnosed AML patients.
      Flow cytometry analyses indicated that icaritin induces AML cells apoptosis.
      Icaritin induced activation of caspase-9, -3, -7 and the cleavage of PARP as
      measured by Western blotting. Icaritin downregulates p-ERK and p-AKT and inhibits
      the expression of c-myc. These results suggest that icaritin is a promising
      candidate drug for the treatment of AML. The underlying mechanisms of icaritin
      anti-AML activity are associated with inhibition of the MAPK/ERK and PI3K/AKT
      signals and downregulation of c-myc.

PMID- 23550022
TI  - Stem cell maintenance and disease progression in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a cancer of blood cells driven by the BCR-ABL1
      oncogenic protein tyrosine kinase, which is the product of a reciprocal
      chromosomal translocation known as the Philadelphia chromosome. Discovery of
      tyrosine kinase inhibitors targeting the BCR-ABL1 kinase revolutionized CML
      therapy, but these drugs are unable to eradicate the disease due to the presence
      of a drug-insensitive stem cell population that sustains continued growth of the
      malignant cells. Resistance to therapies also increases the risk of relapse and
      disease progression to a more advanced phase. This review discusses emerging
      issues in CML research, and describes recent progress in elucidating the
      mechanisms of CML stem cell maintenance and disease progression. 

PMID- 23550023
TI  - Favorable outcome in a child with EBV-negative aggressive NK cell leukemia.
AB  - Aggressive natural killer cell leukemia (ANKL) is a rare malignant disorder of
      mature NK cells frequently associated with Epstein-Barr virus (EBV). This
      malignancy is typically treated with intensive remission induction chemotherapy
      followed by allogeneic hematopoietic stem cell transplantation (HSCT). EBV
      negative ANKL and childhood ANKL, however, are not well defined and the optimal
      therapeutic strategy in these cases is poorly understood. Here, we present a
      unique pediatric EBV-negative ANKL patient who achieved a successful treatment
      outcome after intensified ALL type chemotherapy without allogeneic HSCT.

PMID- 23550024
TI  - Delayed meconium passage in small vs. appropriate for gestational age preterm
      infants: management and short-term outcome.
AB  - OBJECTIVE: Delayed passage of stool is a result of both gestational immaturity
      and illness severity. Small for gestational age (SGA) preterm infants are at high
      risk of gastrointestinal (GI) complications. We aimed to analyse the effects of a
      strict nutrition and stool protocol on GI problems in SGA compared to appropriate
      for gestational age (AGA) preterm infants. METHODS: Retrospective cohort analysis
      including all preterm infants with delayed meconium passage hospitalized at the
      Neonatal Intensive Care Unit of the Medical University of Graz, Austria. Infants
      were identified by a local data system and by the use of a strict feeding and
      stool protocol between 2001 and 2009. Main outcome parameters included neonatal
      morbidity, surgical intervention and mortality. FINDINGS: Twenty-six SGA (median
      GA 28.6 weeks, birth weight 825 grams, 46% males) were compared to 101 AGA
      (median GA 28.4 weeks, birth weight 1168 grams, 55% males) preterm infants.
      Clinical signs of delayed meconium passage did not differ significantly between
      groups. Differences regarding percentage of necrotizing enterocolitis, ileus,
      spontaneous intestinal perforation, and surgical intervention did not differ
      between groups. Mortality rate was significantly higher in SGA (11.5%) compared
      to AGA (2.9%) infants (P=0.03). CONCLUSION: Despite similar morbidity SGA infants
      exhibited higher lethal complication rates following delayed meconium passage
      compared to AGA infants.

PMID- 23550025
TI  - Development of a preclinical PK/PD model to assess antitumor response of a
      sequential aflibercept and doxorubicin-dosing strategy in acute myeloid leukemia.
AB  - Timing of the anti-angiogenic agent with respect to the chemotherapeutic agent
      may be crucial in determining the success of combination therapy in cancer. We
      investigated the effects of sequential therapy with the potent VEGF inhibitor,
      aflibercept, and doxorubicin (DOX) in preclinical acute myeloid leukemia (AML)
      models. Mice were engrafted with human HL-60 and HEL-luciferase leukemia cells
      via S.C. and/or I.V. injection and treated with two to three doses of aflibercept
      (5-25 mg/kg) up to 3-7 days prior to doxorubicin (30 mg/kg) administration.
      Leukemia growth was determined by local tumor measurements (days 0-16) and
      systemic bioluminescent imaging (days 0-28) in animals receiving DOX (3 mg/kg)
      with or without aflibercept. A PK/PD model was developed to characterize how
      prior administration of aflibercept altered intratumoral DOX uptake. DOX
      concentration-time profiles were described using a four-compartment PK model with
      linear elimination. We determined that intratumoral DOX concentrations were 6
      fold higher in the aflibercept plus DOX treatment group versus DOX alone in
      association with increased drug uptake rates (from 0.125 to 0.471 ml/h/kg) into
      tumor without affecting drug efflux. PD modeling demonstrated that the observed
      growth retardation was mainly due to the combination of DOX plus TRAP group;
      0.00794 vs. 0.0043 h(-1). This PK/PD modeling approach in leukemia enabled us to
      predict the effects of dosing frequency and sequence for the combination of anti
      VEGF and cytotoxic agents on AML growth in both xenograft and marrow, and may be
      useful in the design of future rational combinatorial dosing regimens in
      hematological malignancies. 

PMID- 23550026
TI  - BDNF-TrkB signaling pathway is involved in pentylenetetrazole-evoked progression
      of epileptiform activity in hippocampal neurons in anesthetized rats.
AB  - Pentylenetetrazole (PTZ) is a widely-used convulsant used in studies of epilepsy;
      its subcutaneous injection generates an animal model with stable seizures. Here,
      we compared the ability of PTZ via the intravenous and subcutaneous routes to
      evoke progressive epileptiform activity in the hippocampal CA1 neurons of
      anesthetized rats. The involvement of the BDNF-TrkB pathway was then
      investigated. When PTZ was given intravenously, it induced epileptiform bursting
      activity at a short latency in a dose-dependent manner. However, when PTZ was
      given subcutaneously, it induced a slowly-developing pattern of epileptogenesis;
      first, generating multiple population-spike peaks, then spontaneous interictal
      discharge-like spike, leading to the final ictal discharge-like, highly
      synchronized bursting fi ring in the CA1 pyramidal layer of the hippocampus.
      K252a, a TrkB receptor antagonist, when given by intracerebroventricular
      injection, significantly reduced the probability of multiple population spike
      peaks induced by subcutaneous injection of PTZ, delayed the latency of
      spontaneous spikes, and reduced the burst frequency. Our results indicate that
      PTZ induces a progressive change of neuronal epileptiform activity in the
      hippocampus, and the BDNF-TrkB signaling pathway is mainly involved in the early
      phases of epileptogenesis, but not the synchronized neuronal burst activity
      associated with epileptic seizure in the PTZ animal model. These results provide
      basic insights into the changing pattern of hippocampal neuronal activity during
      the development of the PTZ seizure model, and establish an in vivo seizure model
      useful for future electrophysiological studies of epilepsy.

PMID- 23550027
TI  - Relationship between free fatty acids, insulin resistance markers, and oxidized
      lipoproteins in myocardial infarction and acute left ventricular failure.
AB  - BACKGROUND: The most common cause of myocardial infarction (MI) is stenotic
      atherosclerotic lesions in subepicardial coronary arteries. Artery disease
      progression induces clinical signs and symptoms, among which MI is the leader in
      mortality and morbidity. Recent studies have been trying to find new biochemical
      markers that could predict the evolution of clinical complications; among those
      markers, free fatty acids (FFA) and oxidative modification of low-density
      lipoproteins (oxidized LDL) have a special place. MATERIALS AND METHODS: Seventy
      nine ST-elevation MI patients were enrolled. The first group included MI patients
      without the signs of acute heart failure (Killip class I) while MI patients with
      Killip classes II-IV made up the second group. Thirty-three individuals with no
      cardiovascular disease were the controls. The lipid profile, serum oxidized LDL,
      and their antibodies, C-peptide and insulin were measured at days 1 and 12. The
      level of insulin resistance was assessed with the quantitative insulin
      sensitivity check index (QUICKI). RESULTS: MI patients had atherogenic
      dyslipidemia; however, the Killip II-IV group had the most pronounced and
      prolonged increase in FFA, oxidized LDL, and their antibodies. Additionally,
      positive correlations between FFA levels and creatine kinase activity (12 days, R
      = 0.301; P = 0.001) and negative correlations between the QUICKI index and FFA
      levels (R = -0.46; P = 0.0013 and R = -0.5; P = 0.01) were observed in the both
      groups. CONCLUSION: The development of MI complications is accompanied by a
      significant increase in FFA levels, which not only demonstrate myocardial injury,
      but also take part in development of insulin resistance. Measuring FFA levels can
      have a great prognostic potential for risk stratification of both acute and
      recurrent coronary events and choice of treatment strategy.

PMID- 23550028
TI  - 2-hydroxy-3-methylanthraquinone from Hedyotis diffusa Willd induces apoptosis in
      human leukemic U937 cells through modulation of MAPK pathways.
AB  - The herb of Hedyotis diffusa Willd (H. diffusa Willd), an annual herb distributed
      in northeastern Asia, has been known as a traditional oriental medicine for the
      treatment of cancer. Recently, Chinese researchers have discovered that two
      anthraquinones isolated from a water extract of H. diffusa Willd showed apoptosis
      inducing effects against cancer cells. However, the cellular and molecular
      mechanisms responsible for this phenomenon are poorly understood. The current
      study determines the role of mitogen-activated protein kinases (MAPK) in human
      leukemic U937 cells apoptosis induced by 2-hydroxy-3-methylanthraquinone from H.
      diffusa. Our results showed that 2-hydroxy-3-methylanthraquinone decreased
      phosphorylation-ERK1/2 (p-ERK1/2), and increased p-p38MAPK, but did not affect
      expressions of p-JNK1/2 in U937 cells. Moreover, treatment of U937 cells with 2
      hydroxy-3-methylanthraquinone resulted in activation of caspase-3. Furthermore,
      PD98059 (ERK1/2 inhibitor) significantly enhanced 2-hydroxy-3-methylanthraquinone
      induced apoptosis in U937 cells, whereas caspase-3 inhibitor or SB203580 (p
      p38MAPK inhibitor), decreased apoptosis in U937 cells. Taken together, our study
      for the first time suggests that 2-hydroxy-3-methylanthraquinone is able to
      enhance apoptosis of U937 cells, at least in part, through activation of p
      p38MAPK and downregulation of p-ERK1/2. Moreover, the triggering of caspase-3
      activation mediated apoptotic induction.

PMID- 23550029
TI  - Microsphere embolisation as an alternative for alcohol in percutaneous
      transluminal septal myocardial ablation.
AB  - BACKGROUND: Percutaneous transluminal septal myocardial ablation using
      microsphere embolisation is a new interventional technique to treat patients with
      hypertrophic obstructive cardiomyopathy. METHODS AND RESULTS: In two patients,
      considered at high risk for myectomy, targeted septal perforators were occluded
      with microsphere embolisation instead of alcohol ablation to reduce left
      ventricular outflow gradient. In both cases the left ventricular outflow tract
      gradient was immediately reduced. No adverse events occurred. CONCLUSION: This is
      the first clinical experience with Embozene(r) Microspheres in the Netherlands as
      an alternative for alcohol septal ablation. In both cases it resulted in
      immediate improvement in the haemodynamics, without any adverse events.

PMID- 23550030
TI  - Quantum Dynamics in Continuum for Proton Transport I: Basic Formulation.
AB  - Proton transport is one of the most important and interesting phenomena in living
      cells. The present work proposes a multiscale/multiphysics model for the
      understanding of the molecular mechanism of proton transport in transmembrane
      proteins. We describe proton dynamics quantum mechanically via a density
      functional approach while implicitly model other solvent ions as a dielectric
      continuum to reduce the number of degrees of freedom. The densities of all other
      ions in the solvent are assumed to obey the Boltzmann distribution. The impact of
      protein molecular structure and its charge polarization on the proton transport
      is considered explicitly at the atomic level. We formulate a total free energy
      functional to put proton kinetic and potential energies as well as electrostatic
      energy of all ions on an equal footing. The variational principle is employed to
      derive nonlinear governing equations for the proton transport system. Generalized
      Poisson-Boltzmann equation and Kohn-Sham equation are obtained from the
      variational framework. Theoretical formulations for the proton density and proton
      conductance are constructed based on fundamental principles. The molecular
      surface of the channel protein is utilized to split the discrete protein domain
      and the continuum solvent domain, and facilitate the multiscale
      discrete/continuum/quantum descriptions. A number of mathematical algorithms,
      including the Dirichlet to Neumann mapping, matched interface and boundary
      method, Gummel iteration, and Krylov space techniques are utilized to implement
      the proposed model in a computationally efficient manner. The Gramicidin A (GA)
      channel is used to demonstrate the performance of the proposed proton transport
      model and validate the efficiency of proposed mathematical algorithms. The
      electrostatic characteristics of the GA channel is analyzed with a wide range of
      model parameters. The proton conductances are studied over a number of applied
      voltages and reference concentrations. A comparison with experimental data
      verifies the present model predictions and validates the proposed model.

PMID- 23550031
TI  - Macular and peripapillary retinal nerve fiber layer thickness in children with
      hyperopic anisometropic amblyopia.
AB  - AIM: To compare the retinal nerve fiber layer (RNFL) thickness and macular
      thickness in the amblyopic eye with that in the sound eye of children with
      hyperopic anisometropic amblyopia using optical coherence tomography (OCT).
      METHODS: A prospective, nonrandom, intraindividual comparative cohort study
      includes 72 children with hyperopic anisometropic amblyopia in a single center.
      Macular thickness, macular foveola thickness, and peripapillary RNFL thickness
      were compared between the amblyopia eyes and the contralateral sound eyes.
      RESULTS: There were 38 male and 34 female patients, with a mean age as 9.7+/-1.9
      years (range, 5-16 years). Hyperopic was +3.62+/-1.16D (range +2.00D to +6.50D)
      in the amblyopic eyes, which was significantly higher in the control eyes with
      +0.76+/-0.90D (range 0D to +2.00D) (P < 0.01). The mean peripapillary RNFL
      thickness was 113.9+/-7.2um and 109.2+/-6.9um in the amblyopic eye and the normal
      eye, respectively, reaching statistical significance (P = 0.02). The mean macular
      foveola thickness was significantly thicker in the amblyopic eyes than the
      contralateral sound eyes (181.4+/-14.2um vs 175.2+/-13.3um, P < 0.01), but the
      1mm, 3mm or 6mm macular thickness central macular thickness was not significantly
      different. Degree of anisometropia in the contralateral eyes was not
      significantly correlated with differences of peripapillary RNFL, macular foveola
      thickness or central macular thickness. CONCLUSION: Eyes with hyperopic
      anisometropic amblyopia are found thicker macular foveola and peripapillary RNFL
      than the contralateral eyes in children.

PMID- 23550032
TI  - On the transposon origins of mammalian SCAND3 and KRBA2, two zinc-finger genes
      carrying an integrase/transposase domain.
AB  - SCAND3 and KRBA2 are two mammalian proteins originally described as "cellular
      integrases" due to sharing of a similar DDE-type integrase domain whose origin
      and relationship with other recombinases remain unclear. Here we perform
      phylogenetic analyses of 341 integrase/transposase sequences to reveal that the
      integrase domain of SCAND3 and KRBA2 derives from the same clade of GINGER2, a
      superfamily of cut-and-paste transposons widely distributed in insects and other
      protostomes, but seemingly absent or extinct in vertebrates. Finally, we
      integrate the results of phylogenetic analyses to the taxonomic distribution of
      SCAND3 and KRBA2 and their transposon relatives to discuss some of the processes
      that promoted the emergence of these two chimeric genes during mammalian
      evolution.

PMID- 23550033
TI  - Psychometric properties of the Exercise Self-efficacy Scale in Dutch Primary care
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Excercise self-efficacy is believed to influence physical activity
      bahavior. PURPOSE: The purpose of this study is to assess the psychometric
      aspects of the Exercise Self-efficacy Scale (ESS) in a type 2 diabetes Dutch
      Primary care sample. METHOD: Type 2 diabetes patients (n = 322; <80 years old)
      filled in the ESS and the short questionnaire to assess health enhancing physical
      activity (SQUASH). The structural validity of the ESS was assessed by means of
      principal axis factor analyses and confirmatory factor analysis. In addition,
      reliability and concurrent validity with the SQUASH outcomes "total" and "leisure
      time minutes/week of moderate to vigorous intensity physical activity" were
      evaluated. T tests and ANOVAs were used to examine ESS scores in subgroups. In
      addition, a 13-item version of the ESS was developed. RESULTS: Analyses were
      performed on complete cases (n = 255). Exploratory factor analysis suggested one
      underlying factor (total explained variance 54 %), with good internal consistency
      (alpha = 0.95). Confirmatory factor analysis showed a poor fit, as did a three
      factor model suggested in an earlier research. Therefore, a 13-item ESS was
      developed with one underlying factor (total explained variance 59 %) and good
      internal consistency (alpha = 0.95). Both the 18-item and 13-item ESS correlated
      significantly with total and leisure time physical activity. ESS scores differed
      significantly between categories of education level and physical activity level.
      CONCLUSION: The 13-item ESS had sound psychometric properties in a large sample
      of primary care type 2 diabetes patients. The 13-item ESS could be useful in
      (intervention) research on physical activity in type 2 diabetes patients.

PMID- 23550034
TI  - Risk factors for first venous thromboembolism around pregnancy: a population
      based cohort study from the United Kingdom.
AB  - Knowledge of the absolute risk (AR) for venous thromboembolism (VTE) in women
      around pregnancy and how potential risk factors modify this risk is crucial in
      identifying women who would benefit most from thromboprophylaxis. We examined a
      large primary care database containing 376 154 pregnancies ending in live birth
      or stillbirth from women aged 15 to 44 years between 1995 and 2009 and assessed
      the effect of risk factors on the incidence of antepartum and postpartum VTE in
      terms of ARs and incidence rate ratios (IRR), using Poisson regression. During
      antepartum, varicose veins, inflammatory bowel disease (IBD), urinary tract
      infection, and preexisting diabetes were associated with an increased risk for
      VTE (ARs, >=139/100 000 person-years; IRRs, >=1.8/100 000 person-years).
      Postpartum, the strongest risk factor was stillbirth (AR, 2444/100 000 person
      years; IRR, 6.2/100 000 person-years), followed by medical comorbidities
      (including varicose veins, IBD, or cardiac disease), a body mass index (BMI) of
      30 kg/m(2) or higher, obstetric hemorrhage, preterm delivery, and caesarean
      section (ARs, >=637/100 000 person-years; IRRs, >=1.9/100 000 person-years). Our
      findings suggest that VTE risk varies modestly by recognized factors during
      antepartum; however, women with stillbirths, preterm births, obstetric
      hemorrhage, caesarean section delivery, medical comorbidities, or a BMI of 30
      kg/m(2) or higher are at much higher risk for VTE after delivery. These risk
      factors should receive careful consideration when assessing the potential need
      for thromboprophylaxis during the postpartum period.

PMID- 23550036
TI  - A functional BCR in human IgA and IgM plasma cells.
AB  - Plasma cells (PCs) are terminally differentiated cells of the B-cell lineage that
      secrete antibodies at a high rate and are thought to lack the expression of the B
      cell receptor (BCR). Here, we report that human IgA and IgM, unlike IgG, PCs
      express a membrane functional BCR associated with the Igalpha/Igbeta heterodimer.
      BCR cross-linking on IgA and IgM PCs led to Ca(2+) mobilization and extracellular
      signal-regulated kinase 1/2 and AKT phosphorylation and impacted survival of IgA
      PCs. These findings demonstrate a significant difference between human IgG, IgM,
      and IgA PCs and suggest that the IgA PC repertoire may be modulated by specific
      antigens with implications for the regulation of the mucosal immune system.

PMID- 23550035
TI  - The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration
      through platelet thrombi.
AB  - Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to
      organ injury in a broad range of diseases; however, the mechanisms by which
      thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using
      mouse models of endothelial injury (traumatic or ischemia reperfusion), we
      demonstrate a distinct process of leukocyte recruitment, termed "directed
      intravascular migration," specifically mediated by platelet thrombi. Single
      adherent platelets and platelet aggregates stimulated leukocyte shape change at
      sites of endothelial injury; however, only thrombi were capable of inducing
      directed intravascular leukocyte migration. Leukocyte recruitment and migration
      induced by platelet thrombi occurred most prominently in veins but could also
      occur in arteries following ischemia-reperfusion injury. In vitro studies
      demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2
      receptor in regulating leukocyte polarization and motility. In vivo studies
      demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus
      body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2
      markedly reduced leukocyte shape change and intrathrombus migration. These
      studies define a distinct process of leukocyte migration that is initiated by
      homotypic adhesive interactions between platelets, leading to the development of
      an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to
      sites of vascular injury.

PMID- 23550037
TI  - Acute and severe coagulopathy in adult mice following silencing of hepatic
      antithrombin and protein C production.
AB  - Mice deficient in the anticoagulants antithrombin (Serpinc1) or protein C (Proc)
      display premature death due to thrombosis-related coagulopathy, thereby
      precluding their use in gene function studies and thrombosis models. We used RNA
      interference to silence Serpinc1 and/or Proc in normal adult mice. The severe
      coagulopathy that followed combined "knockdown" of these genes is reported. Two
      days after siRNA injection, thrombi (occlusive) were observed in vessels (large
      and medium-sized) in multiple tissues, and hemorrhages were prominent in the
      ocular, mandibular, and maxillary areas. Tissue fibrin deposition and reduction
      of plasma fibrinogen accompanied this phenotype. The coagulopathy was prevented
      by dabigatran etexilate treatment. Silencing of Serpinc1 alone yielded a
      comparable but milder phenotype with later onset. The phenotype was absent when
      Proc was targeted alone. We conclude that RNA interference of Serpinc1 and/or
      Proc allows for evaluation of the function of these genes in vivo and provides a
      novel, controlled mouse model for spontaneous venous thrombosis.

PMID- 23550038
TI  - Geriatric assessment predicts survival for older adults receiving induction
      chemotherapy for acute myelogenous leukemia.
AB  - We investigated the predictive value of geriatric assessment (GA) on overall
      survival (OS) for older adults with acute myelogenous leukemia (AML). Consecutive
      patients >= 60 years with newly diagnosed AML and planned intensive chemotherapy
      were enrolled at a single institution. Pretreatment GA included evaluation of
      cognition, depression, distress, physical function (PF) (self-reported and
      objectively measured), and comorbidity. Objective PF was assessed using the Short
      Physical Performance Battery (SPPB, timed 4-m walk, chair stands, standing
      balance) and grip strength. Cox proportional hazards models were fit for each GA
      measure as a predictor of OS. Among 74 patients, the mean age was 70 years, and
      78.4% had an Eastern Cooperative Oncology Group (ECOG) score <= 1. OS was
      significantly shorter for participants who screened positive for impairment in
      cognition and objectively measured PF. Adjusting for age, gender, ECOG score,
      cytogenetic risk group, myelodysplastic syndrome, and hemoglobin, impaired
      cognition (Modified Mini-Mental State Exam < 77) and impaired objective PF (SPPB
      < 9) were associated with worse OS. GA methods, with a focus on cognitive and PF,
      improve risk stratification and may inform interventions to improve outcomes for
      older AML patients.

PMID- 23550039
TI  - Tribbles in acute leukemia.
AB  - There is growing research interest in the mammalian Tribbles (Trib) family of
      serine/threonine pseudokinases and their oncogenic association with acute
      leukemias. This review is to understand the role of Trib genes in hematopoietic
      malignancies and their potential as targets for novel therapeutic strategies in
      acute myeloid leukemia and acute lymphoblastic leukemia. We discuss the role of
      Tribs as central signaling mediators in different subtypes of acute leukemia and
      propose that inhibition of dysregulated Trib signaling may be therapeutically
      beneficial.

PMID- 23550041
TI  - Circulating microRNAs in hematological diseases: principles, challenges, and
      perspectives.
AB  - The complex microRNA (miRNA) network plays an important role in the regulation of
      cellular processes such as development, differentiation, and apoptosis. Recently,
      the presence of cell-free miRNAs that circulate in body fluids was discovered.
      The ability of these circulating miRNAs to mirror physiological and
      pathophysiological conditions as well as their high stability in stored patient
      samples underlines the potential of these molecules to serve as biomarkers for
      various diseases. In this review, we describe recent findings in miRNA-mediated
      cell-to-cell communication and the functions of circulating miRNAs in the field
      of hematology. Furthermore, we discuss current approaches to design biomarker
      studies with circulating miRNAs. This article critically reviews the novel field
      of circulating miRNAs and highlights their suitability for clinical and basic
      research in addition to their potential as a novel class of biomarkers.

PMID- 23550040
TI  - Bleeding manifestations and management of children with persistent and chronic
      immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study
      Group (ICIS).
AB  - Long-term follow-up of children with immune thrombocytopenia (ITP) indicates that
      the majority undergo remission and severe thrombocytopenia is infrequent. Details
      regarding bleeding manifestations, however, remain poorly categorized. We report
      here long-term data from the Intercontinental Cooperative ITP Study Group
      Registry II focusing on natural history, bleeding manifestations, and management.
      Data on 1345 subjects were collected at diagnosis and at 28 days, 6, 12, and 24
      months thereafter. Median platelet counts were 214 * 10(9)/L (interquartile range
      [IQR] 227, range 1-748), 211 * 10(9)/L (IQR 192, range 1-594), and 215 * 10(9)/L
      (IQR 198, range 1-598) at 6, 12, and 24 months, respectively, and a platelet
      count <20 * 10(9)/L was uncommon (7%, 7%, and 4%, respectively). Remission
      occurred in 37% of patients between 28 days and 6 months, 16% between 6 and 12
      months, and 24% between 12 and 24 months. There were no reports of intracranial
      hemorrhage, and the most common site of bleeding was skin. In patients with
      severe thrombocytopenia we observed a trend toward more drug treatment with
      increasing number of bleeding sites. Our data support that ITP is a benign
      condition for most affected children and that major hemorrhage, even with
      prolonged severe thrombocytopenia, is rare.

PMID- 23550042
TI  - Prevalence of helicobacter pylori infection in children, a population-based cross
      sectional study in west iran.
AB  - OBJECTIVE: In developing countries, Helicobacter pylori infection is mainly
      acquired during childhood and may be a predisposing factor for peptic ulcer or
      gastric cancer later in life. Noninvasive diagnostic tools are particularly
      useful in children for screening tests and epidemiological studies. We aimed to
      determine the prevalence of H. pylori infection among Kurdish children in
      Sanandaj, West Iran. METHODS: We used a Helicobacter Pylori Stool Antigen (HpSA)
      test to detect H. pylori infection. A questionnaire was used to collect data
      about age, sex, duration of breastfeeding, and family size. A total of 458
      children aged 4 months to 15 years were enrolled in this study. FINDINGS: The
      mean age of enrolled children was 5.6+/-5.4 years. Stool samples were positive
      for H. pylori in 294 (64.2%) children. The prevalence of H. pylori infection
      increased with age (P<0.001). We found a significant increase in the infection
      rate as the family size grew (P=0.005). There was no correlation between a
      positive H. pylori status and gender (P=0.6) or the duration of breastfeeding
      (P=0.8). CONCLUSION: It seems that the prevalence of H. pylori infection is very
      high in children in Sanandaj. It begins at early infancy (before 4th month of
      age) and cumulatively increases with age.

PMID- 23550043
TI  - Working memory and decision processes in visual area v4.
AB  - Recognizing and responding to a remembered stimulus requires the coordination of
      perception, working memory, and decision-making. To investigate the role of
      visual cortex in these processes, we recorded responses of single V4 neurons
      during performance of a delayed match-to-sample task that incorporates rapid
      serial visual presentation of natural images. We found that neuronal activity
      during the delay period after the cue but before the images depends on the
      identity of the remembered image and that this change persists while distractors
      appear. This persistent response modulation has been identified as a diagnostic
      criterion for putative working memory signals; our data thus suggest that working
      memory may involve reactivation of sensory neurons. When the remembered image
      reappears in the neuron's receptive field, visually evoked responses are
      enhanced; this match enhancement is a diagnostic criterion for decision. One
      model that predicts these data is the matched filter hypothesis, which holds that
      during search V4 neurons change their tuning so as to match the remembered cue,
      and thus become detectors for that image. More generally, these results suggest
      that V4 neurons participate in the perceptual, working memory, and decision
      processes that are needed to perform memory-guided decision-making.

PMID- 23550044
TI  - Clinical spectrum and therapeutic approach to hepatocellular injury in patients
      with hyperthyroidism.
AB  - Liver dysfunction in patients with hyperthyroidism includes abnormalities
      associated with the effects of thyroid hormone excess, those secondary to drug
      induced liver injury, and changes resulting from concomitant liver disease. Our
      goal was to describe clinical, biochemical, and histopathological patterns in
      patients suffering from hyperthyroidism and concomitant liver dysfunction and to
      propose an algorithm of procedures to facilitate diagnosis and management of such
      cases. This study describes seven patients with liver biochemistry abnormalities
      detected after diagnosis of hyperthyroidism and one with undiagnosed
      decompensated hyperthyroidism and acute hepatitis. Two patients showed
      autoantibody reactivity which, together with liver histology, suggested the
      diagnosis of classic autoimmune hepatitis. Three patients experienced
      hepatotoxicity induced by propylthiouracil, the manifestations of which ranged
      from a benign course after drug withdrawal in one, a longstanding course in
      another suggesting drug-induced autoimmune hepatitis, and a more severe clinical
      condition with acute liver failure in a third patient, requiring liver
      transplantation. The three remaining patients showed no precipitating factors
      other than thyroid hyperactivity itself. They could be interpreted as having a
      thyroid storm with different clinical presentations. In conclusion, this series
      of patients illustrates the most frequent patterns of hepatocellular damage
      associated with hyperthyroidism and provides an algorithm for their diagnosis and
      treatment.

PMID- 23550045
TI  - Vasectomy.

PMID- 23550047
TI  - Doctors and the alcohol industry: an unhealthy mix?

PMID- 23550046
TI  - Clinical prediction model to aid emergency doctors managing febrile children at
      risk of serious bacterial infections: diagnostic study.
AB  - OBJECTIVE: To derive, cross validate, and externally validate a clinical
      prediction model that assesses the risks of different serious bacterial
      infections in children with fever at the emergency department. DESIGN:
      Prospective observational diagnostic study. SETTING: Three paediatric emergency
      care units: two in the Netherlands and one in the United Kingdom. PARTICIPANTS:
      Children with fever, aged 1 month to 15 years, at three paediatric emergency care
      units: Rotterdam (n=1750) and the Hague (n=967), the Netherlands, and Coventry
      (n=487), United Kingdom. A prediction model was constructed using multivariable
      polytomous logistic regression analysis and included the predefined predictor
      variables age, duration of fever, tachycardia, temperature, tachypnoea, ill
      appearance, chest wall retractions, prolonged capillary refill time (>3 seconds),
      oxygen saturation <94%, and C reactive protein. MAIN OUTCOME MEASURES: Pneumonia,
      other serious bacterial infections (SBIs, including septicaemia/meningitis,
      urinary tract infections, and others), and no SBIs. RESULTS: Oxygen saturation
      <94% and presence of tachypnoea were important predictors of pneumonia. A raised
      C reactive protein level predicted the presence of both pneumonia and other SBIs,
      whereas chest wall retractions and oxygen saturation <94% were useful to rule out
      the presence of other SBIs. Discriminative ability (C statistic) to predict
      pneumonia was 0.81 (95% confidence interval 0.73 to 0.88); for other SBIs this
      was even better: 0.86 (0.79 to 0.92). Risk thresholds of 10% or more were useful
      to identify children with serious bacterial infections; risk thresholds less than
      2.5% were useful to rule out the presence of serious bacterial infections.
      External validation showed good discrimination for the prediction of pneumonia
      (0.81, 0.69 to 0.93); discriminative ability for the prediction of other SBIs was
      lower (0.69, 0.53 to 0.86). CONCLUSION: A validated prediction model, including
      clinical signs, symptoms, and C reactive protein level, was useful for estimating
      the likelihood of pneumonia and other SBIs in children with fever, such as
      septicaemia/meningitis and urinary tract infections.

PMID- 23550048
TI  - How the e-patient community helped save my life: an essay by Dave deBronkart.

PMID- 23550049
TI  - Goodbye (and good riddance?) to PCTs.

PMID- 23550050
TI  - Sublingual immunotherapy reduces symptoms of asthma and hay fever, systematic
      review finds.

PMID- 23550051
TI  - Immigrant song.

PMID- 23550052
TI  - Integrative omics analysis reveals the importance and scope of translational
      repression in microRNA-mediated regulation.
AB  - MicroRNAs (miRNAs) are key post-transcriptional regulators that inhibit gene
      expression by promoting mRNA decay and/or suppressing translation. However, the
      relative contributions of these two mechanisms to gene repression remain
      controversial. Early studies favor a translational repression-centric scenario,
      whereas recent large-scale studies suggest a dominant role of mRNA decay in miRNA
      regulation. Here we generated proteomics data for nine colorectal cancer cell
      lines and integrated them with matched miRNA and mRNA expression data to infer
      and characterize miRNA-mediated regulation. Consistent with previous reports, we
      found that 8mer site, site positioning within 3'UTR, local AU-rich context, and
      additional 3' pairing could all help boost miRNA-mediated mRNA decay. However,
      these sequence features were generally not correlated with increased
      translational repression, except for local AU-rich context. Thus the contribution
      of translational repression might be underestimated in recent studies in which
      the analyses were based primarily on the response of genes with canonical 7-8 mer
      sites in 3'UTRs. Indeed, we found that translational repression was involved in
      more than half, and played a major role in one-third of all predicted miRNA
      target interactions. It was even the predominant contributor to miR-138 mediated
      regulation, which was further supported by the observation that differential
      expression of miR-138 in two genetically matched cell lines corresponded to
      altered protein but not mRNA abundance of most target genes. In addition, our
      study also provided interesting insights into colon cancer biology such as the
      possible contributions of miR-138 and miR-141/miR-200c in inducing specific
      phenotypes of SW480 and RKO cell lines, respectively. 

PMID- 23550054
TI  - Grapefruit-medication interactions.

PMID- 23550055
TI  - Grapefruit-medication interactions.

PMID- 23550056
TI  - Pregnancy and isotretinoin therapy.

PMID- 23550057
TI  - Pregnancy and isotretinoin therapy.

PMID- 23550053
TI  - DISC1 genetics, biology and psychiatric illness.
AB  - Psychiatric disorders are highly heritable, and in many individuals likely arise
      from the combined effects of genes and the environment. A substantial body of
      evidence points towards DISC1 being one of the genes that influence risk of
      schizophrenia, bipolar disorder and depression, and functional studies of DISC1
      consequently have the potential to reveal much about the pathways that lead to
      major mental illness. Here, we review the evidence that DISC1 influences disease
      risk through effects upon multiple critical pathways in the developing and adult
      brain.

PMID- 23550058
TI  - Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its
      cellular distribution.
AB  - Monocarboxylate transporter 8 (MCT8) is a thyroid hormone (TH)-specific
      transporter. Mutations in the MCT8 gene are associated with Allan-Herndon-Dudley
      Syndrome (AHDS), consisting of severe psychomotor retardation and disturbed TH
      parameters. To study the functional consequences of different MCT8 mutations in
      detail, we combined functional analysis in different cell types with live-cell
      imaging of the cellular distribution of seven mutations that we identified in
      patients with AHDS. We used two cell models to study the mutations in vitro: 1)
      transiently transfected COS1 and JEG3 cells, and 2) stably transfected Flp-in 293
      cells expressing a MCT8-cyan fluorescent protein construct. All seven mutants
      were expressed at the protein level and showed a defect in T3 and T4 transport in
      uptake and metabolism studies. Three mutants (G282C, P537L, and G558D) had
      residual uptake activity in Flp-in 293 and COS1 cells, but not in JEG3 cells.
      Four mutants (G221R, P321L, D453V, P537L) were expressed at the plasma membrane.
      The mobility in the plasma membrane of P537L was similar to WT, but the mobility
      of P321L was altered. The other mutants studied (insV236, G282C, G558D) were
      predominantly localized in the endoplasmic reticulum. In essence, loss of
      function by MCT8 mutations can be divided in two groups: mutations that result in
      partial or complete loss of transport activity (G221R, P321L, D453V, P537L) and
      mutations that mainly disturb protein expression and trafficking (insV236, G282C,
      G558D). The cell type-dependent results suggest that MCT8 mutations in AHDS
      patients may have tissue-specific effects on TH transport probably caused by
      tissue-specific expression of yet unknown MCT8-interacting proteins.

PMID- 23550059
TI  - Expression profiling of nuclear receptors identifies key roles of NR4A subfamily
      in uterine fibroids.
AB  - Uterine fibroids (UFs), also known as uterine leiomyomas, are benign, fibrotic
      smooth muscle tumors. Although the GnRH analog leuprolide acetate that suppresses
      gonadal steroid hormones is used as a treatment, it has significant side effects,
      thereby limiting its use. Availability of more effective therapy is limited
      because of a lack of understanding of molecular underpinnings of the disease.
      Although ovarian steroid hormones estrogen and progesterone and their receptors
      are clearly involved, the role of other nuclear receptors (NRs) in UFs is not
      well defined. We used quantitative real-time PCR to systematically profile the
      expression of 48 NRs and identified several NRs that were aberrantly expressed in
      UFs. Among others, expression of NR4A subfamily members including NGFIB (NR4A1),
      NURR1 (NR4A2), and NOR1 (NR4A3) were dramatically suppressed in leiomyoma
      compared with the matched myometrium. Restoration of expression of each of these
      NR4A members in the primary leiomyoma smooth muscle cells decreased cell
      proliferation. Importantly, NR4As regulate expressions of the profibrotic factors
      including TGFbeta3 and SMAD3, and several collagens that are key components of
      the extracellular matrix. Finally, we identify NR4A members as targets of
      leuprolide acetate treatment. Together, our results implicate several NRs
      including the NR4A subfamily in leiomyoma etiology and identify NR4As as
      potential therapeutic targets for treating fibrotic diseases.

PMID- 23550060
TI  - Evaluation of peripapillary retinal nerve fiber layer, macula and ganglion cell
      thickness in amblyopia using spectral optical coherence tomography.
AB  - AIM: To investigate peripapillary retinal nerve fiber layer (RNFL), macula and
      ganglion cell layer thicknesses (GCC) in amblyopic eyes with spectral domain
      optical coherence tomography (SD-OCT). METHODS: Thirty six patients with a
      history of unilateral amblyopia and thirty two children who had emmetropia
      without amblyopia were included in this study. In this institutional study, 36
      eyes of 36 patients with amblyopia (AE), 36 fellow eyes without amblyopia (FE),
      and 32 eyes of 32 normal subjects (NE) were included. RNFL, GCC and macular
      thickness measurements were performed with RS-3000 OCT Retina Scan (Nidek Inc CA.
      USA). RESULTS: The mean global thicknesses of the RNFL were 113.22+/-21.47,
      111.57+/-18.25, 109.96+/-11.31um in the AE, FE, and NE, respectively. There was
      no statistically significant difference for mean global RNFL thickness among the
      eyes (P=0.13). The mean thicknesses of the macula were 258.25+/-18.31, 258.75+/
      19.54, 248.62+/-10.57um in the AE, FE and NE, respectively. There was no
      statistically significant difference for thickness of macula among the eyes
      (P=0.06). The GCC was investigated into two parts: superior and inferior. The
      mean thicknesses of superior GCC were 102.57+/-13.32, 103.32+/-10.64, 100.52+/
      5.88um in the AE, FE, and NE, respectively. The mean thicknesses of inferior GCC
      were 103.82+/-12.60, 107.82+/-12.33, 105.86+/-10.79um in the AE, FE and NE,
      respectively. There was no statistically significant difference for thickness of
      superior and inferior GCC between the eyes (P=0.63, P=0.46). CONCLUSION: The
      macular thicknesses of AE and FE were greater than the NE, although it was not
      statistically significant. Amblyopia does not seem to have a profound effect on
      the RNFL, macula and GCC.

PMID- 23550061
TI  - curatedOvarianData: clinically annotated data for the ovarian cancer
      transcriptome.
AB  - This article introduces a manually curated data collection for gene expression
      meta-analysis of patients with ovarian cancer and software for reproducible
      preparation of similar databases. This resource provides uniformly prepared
      microarray data for 2970 patients from 23 studies with curated and documented
      clinical metadata. It allows users to efficiently identify studies and patient
      subgroups of interest for analysis and to perform meta-analysis immediately
      without the challenges posed by harmonizing heterogeneous microarray
      technologies, study designs, expression data processing methods and clinical data
      formats. We confirm that the recently proposed biomarker CXCL12 is associated
      with patient survival, independently of stage and optimal surgical debulking,
      which was possible only through meta-analysis owing to insufficient sample sizes
      of the individual studies. The database is implemented as the curatedOvarianData
      Bioconductor package for the R statistical computing language, providing a
      comprehensive and flexible resource for clinically oriented investigation of the
      ovarian cancer transcriptome. The package and pipeline for producing it are
      available from http://bcb.dfci.harvard.edu/ovariancancer.

PMID- 23550062
TI  - Biological database of images and genomes: tools for community annotations
      linking image and genomic information.
AB  - Genomic data and biomedical imaging data are undergoing exponential growth.
      However, our understanding of the phenotype-genotype connection linking the two
      types of data is lagging behind. While there are many types of software that
      enable the manipulation and analysis of image data and genomic data as separate
      entities, there is no framework established for linking the two. We present a
      generic set of software tools, BioDIG, that allows linking of image data to
      genomic data. BioDIG tools can be applied to a wide range of research problems
      that require linking images to genomes. BioDIG features the following: rapid
      construction of web-based workbenches, community-based annotation, user
      management and web services. By using BioDIG to create websites, researchers and
      curators can rapidly annotate a large number of images with genomic information.
      Here we present the BioDIG software tools that include an image module, a genome
      module and a user management module. We also introduce a BioDIG-based website,
      MyDIG, which is being used to annotate images of mycoplasmas.

PMID- 23550064
TI  - Application of a modified surgical safety checklist: user beware!

PMID- 23550065
TI  - Additive effect of phosphodiesterase inhibitors in control of pulmonary
      hypertension after congenital cardiac surgery in children.
AB  - OBJECTIVE: Control of residual pulmonary arterial hypertension (PAH) after
      closure of left to right shunts in children is still a challenging issue. The
      purpose of this study was to compare the effect of two phosphodiesterase
      inhibitors in pediatric cardiac surgical patients. METHODS: A total of 48
      postoperative children were enrolled in the study between 2008 and 2010. Patients
      were stratified based upon choice of pulmonary vasodilator into three equal
      groups (n = 16); Milrinone group received intravenous milrinone (0.75 u/kg/min),
      Sildenafil group received oral sildenafil (0.3 mg/kg every 3 hours) and the
      Combination group received both medications. FINDINGS: Demographic variables and
      types of congenital anomalies were not different among the 3 groups. Patients in
      the Combination group had higher preoperative pulmonary artery to aortic (PA/AO)
      pressure ratios compared to other two groups (P=0.001). Postoperatively, patients
      in Milrinone group incurred lower systolic PA and PA/AO pressures compared to
      Sildenafil group (P=0.014, 0.003), but it was the same in Sildenafil and
      Combination group (P=0.2; 0.330 respectively). Pulmonary hypertensive crisis was
      noted in 6 patients in Sildenafil group, and 3 patients in Combination group
      (P=0.02). Significant rise in PA pressure was noticed after discontinuation of
      drug in Milrinone group (P=0.001), which was not observed in the Combination
      group (P= 0.6). No mortality was noticed in any of the groups. CONCLUSION:
      Intravenous milrinone is more effective than oral sildenafil in control of
      postoperative PAH and elimination of pulmonary hypertensive crisis. Combination
      of two drugs reduces the risk of rebound pulmonary arterial hypertension after
      discontinuation of milrinone.

PMID- 23550063
TI  - Integrons: Vehicles and pathways for horizontal dissemination in bacteria.
AB  - Integrons are genetic elements first described at the end of the 1980s. Although
      most integrons were initially described in human clinical isolates, they have now
      been identified in many non-clinical environments, such as water and soil.
      Integrons are present in ~10% of the sequenced bacterial genomes and are
      frequently linked to mobile genetic elements (MGEs); particularly the class 1
      integrons. Genetic linkage to a diverse set of MGEs facilitates horizontal
      transfer of class 1 integrons within and between bacterial populations and
      species. The mechanistic aspects limiting transfer of MGEs will therefore limit
      the transfer of class 1 integrons. However, horizontal movement due to genes
      provided in trans and homologous recombination can result in class 1 integron
      dynamics independent of MGEs. A key determinant for continued dissemination of
      class 1 integrons is the probability that transferred MGEs will be vertically
      inherited in the recipient bacterial population. Heritability depends both on
      genetic stability as well as the fitness costs conferred to the host. Here we
      review the factors known to govern the dissemination of class 1 integrons in
      bacteria.

PMID- 23550066
TI  - The CYP2B6*6 allele significantly alters the N-demethylation of ketamine
      enantiomers in vitro.
AB  - Ketamine is primarily metabolized to norketamine by hepatic CYP2B6 and CYP3A4
      mediated N-demethylation. However, the relative contribution from each enzyme
      remains controversial. The CYP2B6*6 allele is associated with reduced enzyme
      expression and activity that may lead to interindividual variability in ketamine
      metabolism. We examined the N-demethylation of individual ketamine enantiomers
      using human liver microsomes (HLMs) genotyped for the CYP2B6*6 allele, insect
      cell-expressed recombinant CYP2B6 and CYP3A4 enzymes, and COS-1 cell-expressed
      recombinant CYP2B6.1 and CYP2B6.6 protein variant. Effects of CYP-selective
      inhibitors on norketamine formation were also determined in HLMs. The two-enzyme
      Michaelis-Menten model best fitted the HLM kinetic data. The Michaelis-Menten
      constants (K(m)) for the high-affinity enzyme and the low-affinity enzyme were
      similar to those for the expressed CYP2B6 and CYP3A4, respectively. The intrinsic
      clearance for both ketamine enantiomers by the high-affinity enzyme in HLMs with
      CYP2B6*1/*1 genotype were at least 2-fold and 6-fold higher, respectively, than
      those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. The V(max) and K(m)
      values for CYP2B6.1 were approximately 160 and 70% of those for CYP2B6.6,
      respectively. N,N'N'-triethylenethiophosphoramide (thioTEPA) (CYP2B6 inhibitor,
      25 MUM) and the monoclonal antibody against CYP2B6 but not troleandomycin (CYP3A4
      inhibitor, 25 MUM) or the monoclonal antibody against CYP3A4 inhibited ketamine N
      demethylation at clinically relevant concentrations. The degree of inhibition was
      significantly reduced in HLMs with the CYP2B6*6 allele (gene-dose P < 0.05).
      These results indicate a major role of CYP2B6 in ketamine N-demethylation in
      vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding
      and catalytic activity.

PMID- 23550067
TI  - The hepatitis B vaccine and celiac disease: more lights than shadows?

PMID- 23550068
TI  - Allow relatives to stay overnight with vulnerable adults to make wards more safe
      for them.

PMID- 23550069
TI  - The John Henry effect.

PMID- 23550070
TI  - Fragmentation of basic and nursing care may be to blame for unsafe wards.

PMID- 23550071
TI  - Only time will tell whether big pharma has an acceptable face.

PMID- 23550072
TI  - Only one handed applause due.

PMID- 23550073
TI  - Surgical embolectomy is underused.

PMID- 23550074
TI  - UK cardiac surgeons have shown the best way to ensure good clinical practice.

PMID- 23550075
TI  - Maintaining registers that provide reliable and valid information is not easy.

PMID- 23550076
TI  - Using positive markers for audit.

PMID- 23550077
TI  - Test for HIV if clinically indicated, regardless of risk factors.

PMID- 23550078
TI  - Suspension of paediatric heart surgery in Leeds provokes controversy.

PMID- 23550079
TI  - Indian Supreme Court rejects Novartis's appeal on drug patent.

PMID- 23550081
TI  - Adiposity and insulin resistance in humans: the role of the different tissue and
      cellular lipid depots.
AB  - Human adiposity has long been associated with insulin resistance and increased
      cardiovascular risk, and abdominal adiposity is considered particularly adverse.
      Intra-abdominal fat is associated with insulin resistance, possibly mediated by
      greater lipolytic activity, lower adiponectin levels, resistance to leptin, and
      increased inflammatory cytokines, although the latter contribution is less clear.
      Liver lipid is also closely associated with, and likely to be an important
      contributor to, insulin resistance, but it may also be in part the consequence of
      the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia
      and unimpaired signaling. Again, intramyocellular triglyceride is associated with
      muscle insulin resistance, but anomalies include higher intramyocellular
      triglyceride in insulin-sensitive athletes and women (vs men). Such issues could
      be explained if the "culprits" were active lipid moieties such as diacylglycerol
      and ceramide species, dependent more on lipid metabolism and partitioning than
      triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears
      metabolically protective, illustrated by insulin resistance and dyslipidemia in
      patients with lipodystrophy. However, some studies suggest that deep sc abdominal
      fat may have adverse properties. Pericardial and perivascular fat relate to
      atheromatous disease, but not clearly to insulin resistance. There has been
      recent interest in recognizable brown adipose tissue in adult humans and its
      possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose
      tissue is metabolically active, oxidizes fatty acids, and generates heat but,
      because of its small and variable quantities, its metabolic importance in humans
      under usual living conditions is still unclear. Further understanding of specific
      roles of different lipid depots may help new approaches to control obesity and
      its metabolic sequelae. 

PMID- 23550080
TI  - Clinical management of nondialysis patients with chronic kidney disease: a
      retrospective observational study. Data from the SONDA study (Survey Of Non
      Dialysis outpAtients).
AB  - BACKGROUND: A lack of awareness of chronic kidney disease (CKD) often results in
      delayed diagnosis and inadequate treatment. PURPOSE: The objective of this study
      was to assess the therapeutic management and outcome of nondialysis CKD patients.
      METHODS: Three hundred ninety-seven patients (54.9% males aged 67.5 +/- 14.6
      years) were retrospectively screened at the Nephrology Department, GB Grassi
      Hospital, Rome, Italy. After a baseline visit, patient data were collected every
      6 months for a total of 24 months. Clinical characteristics were measured at
      baseline, then the following outcomes were measured every 6 months: staging of
      CKD, presence of concomitant diseases, treatment and adherence to Kidney Disease
      Outcomes Quality Initiative (K/DOQI) guidelines for anemia management. RESULTS:
      Three hundred sixty-eight (92.7%) patients attended at least one visit and 92
      (23.2%) patients attended all four visits. Patients were mainly referred to a
      nephrologist for chronic renal failure (61.7%) or hypertension (42.8%). At
      baseline, 79.6% of patients had previous hospitalization and 79.1% were receiving
      antihypertensive medication. Serum creatinine and/or glomerular filtration rate
      was examined in >90% of patients, whereas parathyroid hormone was rarely examined
      (5.5%). Vitamin D supplementation was received by 6.5% of patients. The majority
      of patients were staged at 3 or 4 CKD (32% and 23.9%, respectively) and did not
      significantly change over time. The use of antithrombotic, antilipidemic and
      erythropoietin medication increased over the four surveys. The majority of
      patients (86.8%) achieved hemoglobin K/DOQI target levels. CONCLUSION: These
      findings demonstrate a current lack of attention of CKD and related disorders
      (mineral metabolism, electrolyte balance, and anemia) at the level of the general
      practitioner (GP) and non-nephrology specialist, which can result in both delayed
      referral and inadequate treatment. By increasing both awareness of CKD and the
      coordinated relationship between GPs and nephrologists, patient clinical and
      therapeutic outcome may be improved.

PMID- 23550082
TI  - Brown adipose tissue in adult humans: a metabolic renaissance.
AB  - Brown adipose tissue (BAT) plays a key role in energy homeostasis and
      thermogenesis in animals, conferring protection against diet-induced obesity and
      hypothermia through the action of uncoupling protein 1 (UCP1). Recent metabolic
      imaging studies using positron emission tomography computerized tomography (PET
      CT) scanning have serendipitously revealed significant depots of BAT in the
      cervical-supraclavicular regions, demonstrating persistence of BAT beyond
      infancy. Subsequent cold-stimulated PET-CT studies and direct histological
      examination of adipose tissues have demonstrated that BAT is highly prevalent in
      adult humans. BAT activity correlates positively with increment of energy
      expenditure during cold exposure and negatively with age, body mass index, and
      fasting glycemia, suggesting regulatory links between BAT, cold-induced
      thermogenesis, and energy metabolism. Human BAT tissue biopsies express UCP1 and
      harbor inducible precursors that differentiate into UCP1-expressing adipocytes in
      vitro. These recent discoveries represent a metabolic renaissance for human
      adipose biology, overturning previous belief that BAT had no relevance in adult
      humans. They also have implications for the understanding of the pathogenesis and
      treatment of obesity and its metabolic sequelae.

PMID- 23550083
TI  - Public satisfaction with emergency care rises.

PMID- 23550084
TI  - Introduction of value based pricing may miss its 2014 target, NICE says.

PMID- 23550085
TI  - Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease.
AB  - One of the most overlooked of all serious complications of diabetes is
      cardiovascular autonomic neuropathy. There is now clear evidence that suggests
      activation of inflammatory cytokines in diabetic patients and that these
      correlate with abnormalities in sympathovagal balance. Dysfunction of the
      autonomic system predicts cardiovascular risk and sudden death in patients with
      type 2 diabetes. It also occurs in prediabetes, providing opportunities for early
      intervention. Simple tests that can be carried out at the bedside with real-time
      output of information - within the scope of the practicing physician - facilitate
      diagnosis and allow the application of sound strategies for management. The
      window of opportunity for aggressive control of all the traditional risk factors
      for cardiovascular events or sudden death with intensification of therapy is with
      short duration diabetes, the absence of cardiovascular disease and a history of
      severe hypoglycemic events. To this list we can now add autonomic dysfunction and
      neuropathy, which have become the most powerful predictors of risk for mortality.
      It seems prudent that practitioners should be encouraged to become familiar with
      this information and apply risk stratification in clinical practice. Several
      agents have become available for the correction of functional defects in the
      autonomic nervous system, and restoration of autonomic balance is now possible.

PMID- 23550087
TI  - Relationship between control beliefs, strategy use, and memory performance in
      amnestic mild cognitive impairment and healthy aging.
AB  - OBJECTIVES: Little information is available regarding the extent of strategy use
      and factors that affect strategy use in amnestic mild cognitive impairment
      (aMCI). This study aimed to compare spontaneous strategy use and beliefs about
      the controllability of memory between aMCI and healthy older adult (HOA) samples
      and to explore the relationships between beliefs, strategy use, and memory
      performance for both groups. METHOD: The aMCI and HOA groups each composed of 60
      individuals matched for age and education. The Memory Controllability Inventory
      was used to assess control beliefs, and the extent of semantic clustering on a
      list-learning task provided a measure of spontaneous strategy use. RESULTS: The
      aMCI group endorsed lower control beliefs and demonstrated poorer semantic
      clustering and memory performance compared with the HOA group. Although strategy
      use partially mediated the control beliefs-memory performance relationship for
      the HOA group, this was not replicated for the aMCI group. DISCUSSION: Despite
      the weak relationship between control beliefs and strategy use, and control
      beliefs and memory performance for the aMCI group, the strong relationship
      between strategy use and memory performance provides impetus for further research
      into factors that can be used as a means of enhancing strategy use in
      interventions for aMCI.

PMID- 23550088
TI  - Ups and downs of daily life: age effects on the impact of daily appraisal
      variability on depressive symptoms.
AB  - OBJECTIVES: Day-to-day variability in appraisals has emerged as an index of
      emotion regulation and overall well-being; there is also evidence that such
      emotion regulation processes change with age. We investigate the impact of day-to
      day variability in positive and negative event appraisals on depressive symptoms,
      focusing on (a) how variability and mean appraisal characteristics interact to
      impact well-being and (b) whether these effects differ by age. METHODS:
      Participants from the Notre Dame Study of Health & Well-Being (aged 40-75 years,
      N = 654) completed daily diaries for up to 56 days, along with a global survey.
      Measures included daily data on life events and appraisals and global assessments
      of depressive symptoms (Center for Epidemiologic Studies Depression scale) and
      neuroticism. RESULTS: Both mean and variability components of daily positive and
      negative event appraisals predict global depressive symptoms; mean and
      variability interactions were also significant. The negative appraisal effects
      became less pronounced with age. DISCUSSION: Findings suggest that those in later
      life are better able to manage the impact that their cognitive and emotional
      responses to daily stressors have on depressive symptoms. The results also
      highlight the importance of examining daily variability-in addition to mean
      levels-in understanding the impact of daily events and appraisals on well-being.

PMID- 23550086
TI  - The landscape of RNA polymerase II transcription initiation in C. elegans reveals
      promoter and enhancer architectures.
AB  - RNA polymerase transcription initiation sites are largely unknown in
      Caenorhabditis elegans. The initial 5' end of most protein-coding transcripts is
      removed by trans-splicing, and noncoding initiation sites have not been
      investigated. We characterized the landscape of RNA Pol II transcription
      initiation, identifying 73,500 distinct clusters of initiation. Bidirectional
      transcription is frequent, with a peak of transcriptional pairing at 120 bp. We
      assign transcription initiation sites to 7691 protein-coding genes and find that
      they display features typical of eukaryotic promoters. Strikingly, the majority
      of initiation events occur in regions with enhancer-like chromatin signatures.
      Based on the overlap of transcription initiation clusters with mapped
      transcription factor binding sites, we define 2361 transcribed intergenic
      enhancers. Remarkably, productive transcription elongation across these enhancers
      is predominantly in the same orientation as that of the nearest downstream gene.
      Directed elongation from an upstream enhancer toward a downstream gene could
      potentially deliver RNA polymerase II to a proximal promoter, or alternatively
      might function directly as a distal promoter. Our results provide a new resource
      to investigate transcription regulation in metazoans. 

PMID- 23550089
TI  - Age and interviewer behavior as predictors of interrogative suggestibility.
AB  - OBJECTIVE: The main objective was to explore the influence of interviewer
      behavior-abrupt versus friendly-and the age of participants on interrogative
      suggestibility. METHOD: The study involved 42 young adults and 50 elderly
      participants. The Gudjonsson Suggestibility Scale 2 was used. Data analysis
      involved a 2-factor between-subjects design (interviewer behavior * age) and
      mediation analysis. RESULTS: The scores of elderly participants were
      significantly lower than younger adults on memory indices and significantly
      higher on some suggestibility indexes. Some suggestibility indices in the abrupt
      experimental condition were higher than those in the friendly experimental
      condition. Elderly participants who were interviewed under the abrupt condition
      were more likely to change their answers after receiving negative feedback than
      younger adults. Memory quality was a mediator of the relationship between age and
      the tendency to yield to suggestive questions. Self-appraisal of memory was a
      mediator between both age and interviewer behavior and the tendency to change
      answers after negative feedback. DISCUSSION: Mechanisms of the relationship
      between age, interviewer behavior, and suggestibility are discussed on the basis
      of the mediational analyses. The findings suggest that a friendly manner should
      be adopted when interrogating witnesses.

PMID- 23550090
TI  - Comparison of handheld rebound tonometry with Goldmann applanation tonometry in
      children with glaucoma: a cohort study.
AB  - OBJECTIVE: To test agreement of two methods to measure intraocular pressure
      (IOP): rebound tonometry (RBT) and gold standard Goldmann applanation tonometry
      (GAT) in children with glaucoma. DESIGN: Observational prospective cohort study.
      SETTING: Tertiary paediatric glaucoma clinic at a single centre. PARTICIPANTS:
      102 individuals attending a paediatric glaucoma clinic, mean (SD) age 11.85
      (3.17), of whom 53 were male. PRIMARY AND SECONDARY OUTCOME MEASURES: Intraocular
      pressure, central corneal thickness, child preference for measurement method.
      RESULTS: Limits of agreement for intraobserver and interobserver were,
      respectively, (-2.71, 2.98) mm Hg and (-5.75, 5.97) mm Hg. RBT frequently gave
      higher readings than GAT and the magnitude of disagreement depend on the level of
      IOP being assessed. Differences of 10 mm Hg were not uncommon. RBT was the
      preferred method for 70% of children. CONCLUSIONS: There is poor agreement
      between RBT and GAT in children with glaucoma. RBT frequently and significantly
      overestimates IOP. However, 'normal' RBT readings are likely to be accurate and
      may spare children an examination under anaesthesia (EUA). High RBT readings
      should prompt the practitioner to use another standard method of IOP measurement
      if possible, or consider the RBT measurement in the context of clinical findings
      before referring the child to a specialist clinic or considering EUA.

PMID- 23550091
TI  - Parents' first moments with their very preterm babies: a qualitative study.
AB  - OBJECTIVES: To assess parents' first experiences of their very preterm babies and
      the neonatal intensive care unit (NICU). DESIGN: Qualitative study using
      semistructured interviews. PARTICIPANTS: 32 mothers and 7 fathers of very preterm
      babies (<32 weeks gestation). SETTING: Three neonatal units in tertiary care
      hospitals in South East England. RESULTS: Five themes were identified. The first
      describes parents' blurred recall of the birth. The second shows the anticipation
      of seeing and touching their baby for the first time was characterised by
      contrasting emotions, with some parents feeling scared and others excited about
      the event. The third theme describes parents' first sight and touch of their
      babies and their 'rollercoaster' of emotions during this time. It also highlights
      the importance of touch to trigger and strengthen the parent-baby bond. However,
      some parents were worried that touching or holding the baby might transmit
      infection or interfere with care. The fourth theme captures parents' impressions
      of NICU and how overwhelming this was particularly for parents who had not toured
      NICU beforehand or whose first sight of their baby was on NICU. The final theme
      captures unique experiences of fathers, in particular that many felt excluded and
      confused about their role. CONCLUSIONS: This study informs family-centred care by
      providing insight into the experiences of parents of very preterm infants at a
      time when they are most in need of support. Clinical implications include the
      importance of offering parents preparatory tours of the NICU and including
      fathers.

PMID- 23550092
TI  - Seroprevalence of syphilis among HIV-infected individuals in Addis Ababa,
      Ethiopia: a hospital-based cross-sectional study.
AB  - OBJECTIVE: To determine the prevalence of syphilis and its risk factors among
      people with HIV at a hospital in Ethiopia. DESIGN: A hospital-based cross
      sectional study. SETTING: This study was conducted at one of the largest public
      hospitals in Addis Ababa , Ethiopia. PARTICIPANTS: A consecutive 306 HIV-positive
      patients were recruited prospectively from January to March 2010. For comparative
      purposes, 224 HIV-negative consecutive attendees at the voluntary counselling and
      testing centre in the same period were also included. Participants under 15 years
      of age and treated for syphilis and with a CD4 T-cell count below 50 cells/mm(3)
      were excluded. OUTCOME MEASURES: Blood samples and data on sociodemographic and
      risk factors for syphilis were collected. Sera were screened for syphilis using
      rapid plasma reagin (RPR) test, and those positives were retested using Treponema
      pallidum haemagglutination assay (TPHA) test. RESULTS: The seroprevalence of
      syphilis among HIV-infected individuals was 9.8% compared with 1.3% among HIV
      uninfected individuals, OR 8.01 (95% CI 2.4 to 26.6; p=0.001). A comparable rate
      of syphilis was found among men (11%) and women (8.9%) with HIV infection.
      Syphilis prevalence non-significantly increased with age, with the highest rate
      in 40-49 years of age (16.9%). Except a history of sexually transmitted
      infections, which was associated with syphilis OR 2.25 (95% CI 1.03 to 4.9;
      p=0.042), other risk factors did not raise the odds of infection. CONCLUSIONS:
      The high prevalence of syphilis among people with HIV infection highlights the
      need to target this population to prevent the transmission of both infections.
      Screening all HIV-infected people for syphilis and managing those infected would
      have clinical and epidemiological importance.

PMID- 23550094
TI  - Views of UK-trained medical graduates of 1999-2009 about their first postgraduate
      year of training: national surveys.
AB  - BACKGROUND: In the UK, doctors' first year of medical work is also their first
      year of postgraduate training. It is very important that their experience of work
      and training is good. DESIGN: Surveys of entire cohorts graduating in particular
      years. SETTING: UK. METHOD: Questionnaires sent 1 year after qualification to all
      UK medical graduates of 1999, 2000, 2002, 2005, 2008 and 2009. RESULTS: The study
      comprised 17 831 respondents. Variation in views across cohorts was modest.
      Overall, 30% agreed their training had been of a high standard; 38% agreed
      educational opportunities had been good; 52% agreed they had to do too much
      routine non-medical work; and 16% agreed they had to perform clinical tasks for
      which they felt inadequately trained. Job enjoyment, rated from 1 ('I didn't
      enjoy it at all') to 10 ('I enjoyed it greatly'), improved from 70% of doctors in
      the 1999 cohort scoring 7-10 to 75% in the 2009 cohort. Satisfaction with
      available leisure time, rated from 1 ('not at all satisfied') to 10 ('extremely
      satisfied'), rose from 24% scoring 7-10 in the 1999s to 49% in the 2009s. Male
      female differences were small. CONCLUSIONS: There was improvement over the decade
      in some aspects of work, particularly satisfaction with time off work for
      leisure, and overall enjoyment of the job. There was little change in doctors'
      views about the training experience offered by the F1 year.

PMID- 23550093
TI  - Specificity and sensitivity of transcranial sonography of the substantia nigra in
      the diagnosis of Parkinson's disease: prospective cohort study in 196 patients.
AB  - OBJECTIVE: Numerous ultrasound studies have suggested that a typical enlarged
      area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic
      Parkinson's disease (IPD). Almost all these studies were retrospective and
      involved patients with well-established diagnoses and long-disease duration. In
      this study the diagnostic accuracy of transcranial sonography (TCS) of the
      substantia nigra in the patient with an undiagnosed parkinsonian syndrome of
      recent onset has been evaluated. DESIGN: Prospective cohort study for diagnostic
      accuracy. SETTING: Neurology outpatient clinics of two teaching hospitals in the
      Netherlands. PATIENTS: 196 consecutive patients, who were referred to two
      neurology outpatient clinics for analysis of clinically unclear parkinsonism.
      Within 2 weeks of inclusion all patients also underwent a TCS and a (123)I
      ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176).
      OUTCOME MEASURES: After 2 years, patients were re-examined by two movement
      disorder specialist neurologists for a final clinical diagnosis, that served as a
      surrogate gold standard for our study. RESULTS: Temporal acoustic windows were
      insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD
      in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with
      atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6
      (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4
      (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of
      vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced
      parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative
      diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to
      0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive
      value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The
      sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI
      0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84.
      CONCLUSIONS: The diagnostic accuracy of TCS in early stage Parkinson's disease is
      not sufficient for routine clinical use. CLINICALTRIALS.GOV IDENTIFIER:
      NCT0036819.

PMID- 23550095
TI  - ExPeKT--Exploring prevention and knowledge of venous thromboembolism: a two
      stage, mixed-method study protocol.
AB  - INTRODUCTION: There is little awareness of venous thromboembolism (VTE) in the
      public arena. Most commonly known causes are-travellers' thrombosis and
      thrombosis associated with oral contraception, both frequently referred to in the
      media. However, VTE is a substantial healthcare problem, resulting in mortality,
      morbidity and economic cost. Most hospitalised patients have one or more risk
      factors for VTE. Around 60% of people undergoing hip or knee replacement will
      suffer a deep vein thrombosis without preventative intervention. Studies
      demonstrate a risk reduction for VTE of up to 70% with preventative medicine for
      medical and surgical conditions: cancer, orthopaedic surgery, general surgery and
      acutely ill medical admissions. Results will be used to identify methods of
      increasing knowledge of VTE prevention and for the development of educational and
      patient information materials. METHODS AND ANALYSIS: A two-stage, mixed-method
      study using surveys with primary healthcare professionals and patients followed
      by interviews with primary healthcare professionals, patients, acute trusts and
      other relevant organisations. Survey and qualitative interview data will examine
      the current practice of thromboprophylaxis, and the knowledge and experience of
      VTE prevention for the development of education initiatives for primary
      healthcare professionals and patients to adopt thromboprophylaxis outside the
      hospital setting. As this is a scientific exploratory study for the generation,
      rather than testing, of new hypotheses a sample-size analysis is not called for.
      Survey data will be analysed using SPSS version 20. Open-ended responses will be
      analysed using qualitative thematic methods. The recorded and transcribed
      semistructured interview data will be analysed using constant comparative
      methods. ETHICS AND DISSEMINATION: Ethics approval has been provided by the
      National Research Ethics Committee (reference: 11/H0605/5) and site-specific R&D
      approval granted by the relevant R&D National Health Service trusts. Findings
      will be disseminated at healthcare and academic conferences and written for peer
      reviewed publication. TRIAL GRANT NUMBER: NIHR RP-PG-0608-10073.

PMID- 23550096
TI  - The safety and efficacy of intracoronary nitrite infusion during acute myocardial
      infarction (NITRITE-AMI): study protocol of a randomised controlled trial.
AB  - INTRODUCTION: Acute myocardial infarction (AMI) is a major cause of death and
      disability in the UK and worldwide. Presently, timely and effective reperfusion
      with primary percutaneous coronary intervention (PPCI) remains the most effective
      treatment strategy for limiting infarct size, preserving left ventricular
      ejection fraction (LVEF) and improving clinical outcomes. However, the process of
      reperfusion can itself induce cardiomyocyte death, known as myocardial
      reperfusion injury, for which there is currently no effective therapy. Extensive
      preclinical evidence exists to suggest that sodium nitrite (as a source of
      endogenous nitric oxide) is an effective therapeutic strategy for preventing
      myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether
      sodium nitrite reduces reperfusion injury and subsequent infarct size in patients
      undergoing PPCI for MI. METHODS AND DESIGN: NITRITE-AMI is a double-blind,
      randomised, single-centre, placebo-controlled trial to determine whether
      intracoronary nitrite injection reduces infarct size in patients with myocardial
      infarction undergoing primary angioplasty. The study will enrol 80 patients
      presenting with ST-elevation myocardial infarction. Patients will be randomised
      to receive either a bolus of intracoronary sodium nitrite or placebo (sodium
      chloride) at the time of PPCI. The primary outcome is infarct size assessed by
      creatine kinase area under the curve (AUC) over 48 h. Secondary endpoints include
      troponin T AUC and infarct size, LV dimensions and myocardial salvage index
      assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation,
      the safety and tolerability of intracoronary nitrite, and 1 year major adverse
      cardiac events. ETHICS AND DISSEMINATION: The study is approved by the local
      ethics committee (NRES Committee London West London: 11/LO/1500) and by the
      Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010
      022460-12). The results of the trial will be published according to the CONSORT
      statement and will be presented at conferences and reported in peer-reviewed
      journals. TRIAL REGISTRATION: United Kingdom Clinical Research Network (Study ID
      12117), http://clinicaltrials.gov (NCT01584453) and Current Controlled Trials
      (ISRCTN:38736987).

PMID- 23550097
TI  - The East London glaucoma prediction score: web-based validation of glaucoma risk
      screening tool.
AB  - AIM: It is difficult for Optometrists and General Practitioners to know which
      patients are at risk. The East London glaucoma prediction score (ELGPS) is a web
      based risk calculator that has been developed to determine Glaucoma risk at the
      time of screening. Multiple risk factors that are available in a low tech
      environment are assessed to provide a risk assessment. This is extremely useful
      in settings where access to specialist care is difficult. Use of the calculator
      is educational. It is a free web based service. Data capture is user specific.
      METHOD: The scoring system is a web based questionnaire that captures and
      subsequently calculates the relative risk for the presence of Glaucoma at the
      time of screening. Three categories of patient are described: Unlikely to have
      Glaucoma; Glaucoma Suspect and Glaucoma. A case review methodology of patients
      with known diagnosis is employed to validate the calculator risk assessment.
      RESULTS: Data from the patient records of 400 patients with an established
      diagnosis has been captured and used to validate the screening tool. The website
      reports that the calculated diagnosis correlates with the actual diagnosis 82% of
      the time. Biostatistics analysis showed: Sensitivity = 88%; Positive predictive
      value = 97%; Specificity = 75%. CONCLUSION: Analysis of the first 400 patients
      validates the web based screening tool as being a good method of screening for
      the at risk population. The validation is ongoing. The web based format will
      allow a more widespread recruitment for different geographic, population and
      personnel variables.

PMID- 23550098
TI  - Passport control for foreign integrated DNAs: An unexpected checkpoint by class
      II HDAC4 revealed by amino acid starvation.
AB  - The endless battle between mammalian host cells and microbes has evolved
      mechanisms to shut down the expression of exogenous transcriptional units
      integrated into the genome with the goal of limiting their spreading. Recently,
      we observed that deprivation of essential amino acids leads to a selective,
      reversible upregulation of expression of exogenous transgenes, either carried by
      integrated plasmids or retroviral vectors, but not of their endogenous
      counterparts. This effect was dependent on epigenetic modifications and was
      mediated by the downregulation of the class II histone deacetylase-4 (HDAC4).
      Indeed, HDAC4 expression inversely correlated with that of the transgene and its
      inhibition or downregulation enhanced transgene expression. Could this be true
      also for "naturally" integrated proviruses? We investigated this question in the
      case of HIV-1, the etiological agent of AIDS and we observed that both amino acid
      starvation and HDAC4 inhibition triggered HIV-1 reactivation in chronically
      infected ACH-2 T lymphocytic cells (HDAC4+), but not in similarly infected U1
      promonocytic cells (HDAC4-negative). Thus, an HDAC4-dependent pathway may
      contribute to unleash virus expression by latently infected cells, which
      represent nowadays a major obstacle to HIV eradication. We discuss here the
      implications and open questions of these novel findings, as well as their
      serendipitous prelude.

PMID- 23550099
TI  - Efficacy of Chloral Hydrate and Promethazine for Sedation during
      Electroencephalography in Children; a Randomised Clinical Trial.
AB  - OBJECTIVE: The purpose of this study was to compare efficacy and safety of oral
      chloral hydrate (CH) and promethazine (PZ) for sedation during
      electroencephalography (EEG) in children. METHODS: In a parallel single-blinded
      randomized clinical trial, sixty 1-10 year old children referred to EEG Unit of
      Shahid Sadoughi Hospital from January 2010 to February 2011 in Yazd, Iran, were
      evaluated. They were randomized to receive orally 70 mg/kg chloral hydrate or
      promethazine 1 mg/kg. The primary outcome was efficacy in adequate sedation and
      successful recording of EEG. Secondary outcome included clinical side effects,
      time from administration of the drug to adequate sedation, caregiver's
      satisfaction on a Likert scale, and total stay time in EEG Unit. FINDINGS: Twenty
      four cases with mean age 2.9+/-1.9 years were evaluated. Adequate sedation
      (Ramsay sedation score of four) was obtained in 43.3% of PZ and 100% of CH group
      (P=0.00001). Also in 70% of PZ and 96.7% of CH group, EEG was successfully
      recorded (P=0.006). So, CH was a more effective drug. In CH group, EEG was
      performed in shorter time after taking the drug (32.82+/-9.6 vs 52.14+/-22.88
      minutes, P<0.001) and the parents waited less in the EEG unit (1.29+/-0.54 vs
      2.6+/-0.59 hours, P<0.001). They were also more satisfied (4.6+/-0.6 scores vs
      3.1+/-1.4 scores, P=0.001). Mild side effects such as vomiting in 20% of CH (n =
      6) and agitation in 6.6% of PZ group (n = 2) were seen. No significant difference
      was seen from viewpoint of side effects frequency between the two drugs.
      CONCLUSION: The results of the present study showed that chloral hydrate can be
      considered as a safe and more effective drug in sedation induction for sleep EEG
      in children.

PMID- 23550101
TI  - Exploring beliefs about heart failure treatment in adherent and nonadherent
      patients: use of the repertory grid technique.
AB  - PURPOSE: Beliefs about medicines impact on adherence, but eliciting core beliefs
      about medicines in individual patients is difficult. One method that has the
      potential to elicit individual core beliefs is the "repertory grid technique."
      This study utilized the repertory grid technique to elicit individuals' beliefs
      about their heart failure treatment and to investigate whether generated
      constructs were different between adherent and nonadherent patients. METHODS:
      Ninety-two patients with heart failure were interviewed using a structured
      questionnaire that applied the repertory grid technique. Patients were asked to
      compare and contrast their medicines and self-care activities for their heart
      failure. This lead to the generation of individual constructs (perceptions
      towards medicines), and from these, beliefs were elicited about their heart
      failure treatment, resulting in the generation of a repertory grid. Adherence was
      measured using the Medication Adherence Report Scale (MARS). Patients with a MARS
      score >= 23 were categorized as "adherent" and those with a score <= 22 as
      "nonadherent." The generated grids were analyzed descriptively and constructs
      from all grids themed and the frequency of these constructs compared between
      adherent and nonadherent patients. RESULTS: Individual grids provided insight
      into the different beliefs that patients held about their heart failure
      treatment. The themed constructs "related to water," "affect the heart," "related
      to weight," and "benefit to the heart" occurred more frequently in adherent
      patients compared with nonadherent patients. CONCLUSION: The repertory grid
      technique elicited beliefs of individual participants about the treatment of
      their heart failure. Constructs from self-reported adherent patients were more
      likely to reflect that their medicines and self-care activities were related to
      water and weight, and affect and benefit to the heart. Providing clinicians with
      better insight into individuals' beliefs about their treatment may facilitate the
      development of tailored interventions to improve adherence.

PMID- 23550100
TI  - Neuropsychiatric and psychosocial issues of patients with hepatitis C infection:
      a selective literature review.
AB  - CONTEXT: We briefly reviewed the evidence on the association of hepatitis C (HCV)
      infection with several aspects of mental and psychosocial health. EVIDENCE
      ACQUISITION: Medline was searched with appropriate keywords. The primary sources
      were the systematic reviews. If systematic reviews were not available for a
      subject, then the most relevant and methodologically sound original studies were
      selected. RESULTS: HCV infection is associated with poorer health-related quality
      of life, and physical, mental, and social health. A part of impaired health of
      these patients is related to cirrhosis, intravenous drug use, co morbid
      psychiatric disorders, stigmatization, poor social support, alcohol abuse, and
      interferon treatment. However, HCV itself is also associated with poorer health
      status particularly in the physical and cognitive domains, which might be related
      to brain alterations induced by the virus. Interferon treatment is an important
      cause of depression in HCV patients and sometimes is associated with
      irritability, manic episode, or acute confusional state. Social health of HCV
      patients is significantly impaired by stigmatization, poor social support,
      psychiatric comorbidties, and impaired coping. Psychosocial impairment of HCV
      patients significantly impairs their treatment adherence. A supportive and
      nonjudgmental multidisciplinary team is required for optimal management of these
      patients. CONCLUSIONS: Patients with HCV infection had complex neuropsychiatric
      and psychosocial problems. These problems are challenges for management of HCV
      infection, affect the patient's care significantly, and might alter the course of
      the disease. A multidisciplinary approach, a supportive environment, and a
      nonjudgmental healthcare team are required for optimal medical and psychosocial
      management of patients with HCV.

PMID- 23550102
TI  - Distribution of IL28B Genotypes in Iranian Patients with Chronic Hepatitis C and
      Healthy Individuals.
AB  - BACKGROUND: IL28B polymorphism is recognized as one of the most prominent
      predictors of hepatitis C spontaneous and treatment-induced clearance.
      Interestingly, the favorable genotypes of IL28B are found to be more frequent in
      Asian ethnicity than Caucasian and African populations, respectively. A few
      studies reported that there is a mysterious association between the IL28B
      polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic
      hepatitis C but they did not give any reason for this phenomenon. OBJECTIVES: The
      foremost purpose of this study was to compare the distribution of IL28B genotypes
      between Iranian healthy individuals and patients with chronic hepatitis C.
      PATIENTS AND METHODS: In this study, 921 patients with chronic hepatitis C and
      142 healthy individuals were included. The IL28B rs12979860 and rs8099917
      polymorphisms were genotyped using the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequency of IL28B
      rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%,
      48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the
      frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C
      patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4%
      and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917
      genotypes between patients with chronic hepatitis C and healthy individuals were
      not statistically significant. When we compared the distribution of IL28B
      genotypes between the healthy group and the HCV infected patients by HCV
      genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy
      individuals than HCV genotype 1 infected patients (P = 0.03) however there was no
      significant difference in the distribution of rs12979860 genotypes between the
      healthy and HCV genotype 3 infected groups (P = 0.46). CONCLUSIONS: It seems that
      the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1
      is more prominent than HCV genotype 3 which results in the observation of higher
      rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3
      than HCV genotype 1.

PMID- 23550103
TI  - Anterior vitrectomy and partial capsulectomy via anterior approach to treat
      chronic postoperative endophthalmitis.
AB  - AIM: To describe the results of vitrectomy and partial capsulectomy via anterior
      approach surgical technique in treatment of chronic postoperative endophthalmitis
      (CPE). METHODS: Clinical records of 9 patients treated for CPE between 2006 and
      2010 were reviewed retrospectively. All of these patients were treated with
      vitrectomy and partial capsulectomy via anterior approach. RESULTS: Six of 9
      patients were male. The average patients' age was (60+/-8.1) years. The average
      period between cataract extraction and onset of signs and symptoms was (3.6+/
      1.3) weeks. The average presenting visual acuity was 0.3+/-0.1 and the average
      final post operative visual acuity was 0.7+/-0.2. The mean follow-up period was
      (28.1+/-8.9) weeks. In all patients, the inflammation subsided after surgery.
      CONCLUSION: Our results suggest that anterior vitrectomy and partial capsulectomy
      via anterior approach may be considered as potentially useful and relatively less
      invasive technique to treat CPE.

PMID- 23550104
TI  - Retrotransposons in animal regeneration: Overlooked components of the
      regenerative machinery?
AB  - Research on the involvement of retroelements in developmental processes has been
      gaining momentum recently; however, most of the studies published so far have
      been focused on embryonic development. This commentary presents two recent
      papers, which document significant changes in transcriptional activity of
      retroelements in two different model systems, salamander limb regeneration and
      regeneration of radial organs in the sea cucumber Holothuria glaberrima. We
      hypothesize that transcriptional activity of the retrotransposons can be
      specifically controlled by the host and may play some hitherto unrecognized role
      in regeneration.

PMID- 23550105
TI  - No Moore's Law for batteries.

PMID- 23550107
TI  - Long-term Results of Balloon Pulmonary Valvuloplasty in Children with Congenital
      Pulmonary Valve Stenosis.
AB  - OBJECTIVE: Immediate, short and midterm outcome of balloon pulmonary
      valvuloplasty are well known, but there is limited information on long term
      results. We report long term results of 2-13. 5 years follow up of balloon
      pulmonary valvuloplasty in children. METHODS: From June 1998 to January 2012
      sixty consecutive patients (33 females, 27 males) with moderate to severe valvar
      pulmonary stenosis (right ventricular to pulmonary artery pressure gradient
      greater than 50 mmHg) were considered for balloon valvuloplasty. The gradient was
      measured pre and immediately post-valvuloplasty at catheterization, and then by
      echocardiography at follow up. Follow up studies were performed 2-13.5 years
      (mean+/-SD; 7.1+/-2.5 years, median: 5.5 years) after procedure, by Doppler
      echocardiography in all patients and catheterization and angiography in two
      patients. FINDINGS: Balloon pulmonary valvuloplasty BPV was successful in 53 of
      60 (88.3%) patients whereas surgical valvotomy was necessary in 6 to 60 (10%).
      There was one immediate death due to perforation of the right ventricular outflow
      tract. Pulmonary valve systolic pressure gradient decreased from 83.3+/-32.1 to
      19.3+/-14.2 mmHg immediately after BPV and to 12.3+/-6.6 mmHg at late follow up
      (P<0.001). Pulmonary insufficiency was noted in 20 (38%) patient at short-term,
      but it was demonstrated in 17 (32%) at late follow up. A second valvuloplasty was
      performed in two (3.8%) patients presenting with re-stenosis. CONCLUSION: The
      short, intermediate and long-term outcomes of pulmonary balloon valvuloplasty in
      children are excellent. Therefore it can be considered as the treatment of choice
      for children with pulmonary valve stenosis.

PMID- 23550108
TI  - Distribution of hepatitis C virus genotypes in Iranian chronic infected patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) has different genotypes throughout the world.
      Since the determination of which antiviral treatment to be applied is related to
      HCV genotypes, identification of an individual's HCV genotypes prior to antiviral
      therapy is critical. OBJECTIVES: The purpose of this study was to investigate the
      distribution of HCV genotypes in a large population of Iranian HCV infected
      patients. PATIENTS AND METHODS: Eleven thousand, five hundred and sixty one
      patients with chronic HCV infection which referred to hospitals related to the
      Tehran University of Medical Sciences and Tehran Hepatitis Center-Clinical
      Department of Baqiyatallah Research Center for Gastroeneterology and Liver
      Disease from March 2003 to December 2011 were enrolled. Following extraction of
      viral RNA of the serum, HCV-RNA was detected using reverse transcriptase-nested
      polymerase chain reaction (RT-nested PCR) and then HCV genotypes analyzed by
      restriction fragment length polymorphism (RFLP) assay. RESULTS: The mean age of
      patients was 37.6 +/- 14.2 years (range: 1-87). The highest frequency was noted
      for subtype 1a (44.9%) followed by subtype 3a (39.6%), and 1b (11.3%). Mixed HCV
      genotypes were also found in 2.5% of the total cases. Subtype 1a was the most
      frequent genotype in patients over 40 years of age (46.1% versus 42.4%) and
      subtype 3a was the most frequent in patients under 40 years old (41.5% versus
      38.9%). CONCLUSIONS: This study suggested that the dominant HCV subtype among
      Iranian patients was 1a followed by subtype 3a.

PMID- 23550109
TI  - Inpatient rehabilitation outcome: a matter of diagnosis?
AB  - BACKGROUND: Patients with comorbidities are becoming more and more common in
      Italian rehabilitative wards. These comorbidities are considered a major problem
      for inpatient rehabilitation, due to the fact that they cause longer lengths of
      stay, higher costs, and lower functional results. METHODS: To investigate the
      possible relationships between comorbidity, functional impairment, age, and type
      of discharge in patients hospitalized in postacute rehabilitation facilities, we
      planned an observational study. A total of 178 consecutive inpatients (average
      age: 78 years [range: 39-99]) from postacute rehabilitation facilities were
      recruited. Primary diagnosis, comorbidity rating (Cumulative Illness Rating Scale
      - Geriatric version, CIRS-G) and functional impairment score (Functional
      Independence Measure, FIMTM) were evaluated at admission. The FIMTM rating was
      also assessed at hospital discharge. RESULTS: A total of 178 of the 199 enrolled
      patients completed the rehabilitation treatment (89.4%). The average length of
      stay was 46 +/- 24 days. CIRS-G showed an average comorbidity score for each
      patient of 4.45 +/- 1.69. The average FIMTM rating was 79 +/- 24.88 at admission,
      and 91.9 +/- 25.7 at discharge. Diagnosis at admission (grouped according to the
      International Classification of Diseases 9-CM) seemed to correlate with
      functional results, since lower rehabilitative efficiency was obtained for
      patients who had a history of stroke. CONCLUSION: The number and type of
      comorbidities (CIRS-G) in rehabilitation inpatients do not seem to affect
      functional outcomes of treatment. The determining factor for a lower level of
      functional recovery seems to be the diagnosis at admission.

PMID- 23550110
TI  - Brain. Editorial.

PMID- 23550111
TI  - Human prion diseases: progress in clinical trials.

PMID- 23550112
TI  - Limitations on the developing preterm brain: impact of periventricular white
      matter lesions on brain connectivity and cognition.
AB  - Brain lesions to the white matter in peritrigonal regions, periventricular
      leukomalacia, in children who were born prematurely represent an important model
      for studying limitations on brain development. The lesional pattern is of early
      origin and bilateral, that constrains the compensatory potential of the brain. We
      suggest that (i) topography and severity of periventricular lesions may have a
      long-term predictive value for cognitive and social capabilities in preterm birth
      survivors; and (ii) periventricular lesions may impact cognitive and social
      functions by affecting brain connectivity, and thereby, the dissociable neural
      networks underpinning these functions. A further pathway to explore is the
      relationship between cerebral palsy and cognitive outcome. Restrictions caused by
      motor disability may affect active exploration of surrounding and social
      participation that may in turn differentially impinge on cognitive development
      and social cognition. As an outline for future research, we underscore sex
      differences, as the sex of a preterm newborn may shape the mechanisms by which
      the developing brain is affected.

PMID- 23550113
TI  - Variably protease-sensitive prionopathy in the UK: a retrospective review 1991
      2008.
AB  - Variably protease-sensitive prionopathy is a newly described human prion disease
      of unknown aetiology lying out with the hitherto recognized phenotypic spectrum
      of Creutzfeldt-Jakob disease. Two cases that conform to the variably protease
      sensitive prionopathy phenotype have been identified prospectively in the U.K.
      since the first description of the condition in 2008 in the U.S.A. To determine
      the incidence and phenotype of variably protease-sensitive prionopathy within a
      single well-defined cohort, we have conducted a retrospective review of patients
      referred to the National Creutzfeldt-Jakob Disease Research & Surveillance Unit
      during the period 1991-2008. The approach taken was to screen frozen brain tissue
      by western blotting for the form of protease-resistant prion protein that
      characterizes variably protease-sensitive prionopathy, followed by
      neuropathological and clinical review of candidate cases. Cases diagnosed as
      sporadic Creutzfeldt-Jakob disease with atypical neuropathology were also
      reviewed. Four hundred and sixty-five cases were screened biochemically, yielding
      four candidate cases of variably protease-sensitive prionopathy. One was
      discounted on pathological and clinical grounds, and one was a known case of
      variably protease-sensitive prionopathy previously reported, leaving two new
      cases, which were confirmed biochemically and neuropathologically as variably
      protease-sensitive prionopathy. A third new case that lacked frozen tissue was
      recognized retrospectively on neuropathological grounds alone. This means that
      five cases of variably protease-sensitive prionopathy have been identified
      (prospectively and retrospectively) during the surveillance period 1991-2011 in
      the U.K. Assuming ascertainment levels equivalent to that of other human prion
      diseases, these data indicate that variably protease-sensitive prionopathy is a
      rare phenotype within human prion diseases, which are themselves rare.
      Biochemical investigation indicates that the abnormal protease-resistant prion
      protein fragment that characterizes variably protease-sensitive prionopathy is
      detectable at low levels in some cases of sporadic Creutzfeldt-Jakob disease and
      conversely, that the form of abnormal prion protein that characterizes sporadic
      Creutzfeldt-Jakob disease can be found in certain brain regions of cases of
      variably protease-sensitive prionopathy, indicating molecular overlaps between
      these two disorders.

PMID- 23550114
TI  - The Medical Research Council prion disease rating scale: a new outcome measure
      for prion disease therapeutic trials developed and validated using systematic
      observational studies.
AB  - Progress in therapeutics for rare disorders like prion disease is impeded by the
      lack of validated outcome measures and a paucity of natural history data derived
      from prospective observational studies. The first analysis of the U.K. National
      Prion Monitoring Cohort involved 1337 scheduled clinical assessments and 479
      telephone assessments in 437 participants over 373 patient-years of follow-up.
      Scale development has included semi-quantitative and qualitative carer
      interviews, item response modelling (Rasch analysis), inter-rater reliability
      testing, construct analysis and correlation with several existing scales. The
      proposed 20-point Medical Research Council prion disease rating scale assesses
      domains of cognitive function, speech, mobility, personal care/feeding and
      continence, according to their relative importance documented by carer
      interviews. It is quick and simple to administer, and has been validated for use
      by doctors and nurses and for use over the telephone, allowing for frequent
      assessments that capture the rapid change typical of these diseases. The Medical
      Research Council Scale correlates highly with widely used cognitive and single
      item scales, but has substantial advantages over these including minimal floor
      effects. Three clear patterns of decline were observed using the scale: fast
      linear decline, slow linear decline (usually inherited prion disease) and in some
      patients, decline followed by a prolonged preterminal plateau at very low
      functional levels. Rates of decline and progress through milestones measured
      using the scale vary between sporadic, acquired and inherited prion diseases
      following clinical expectations. We have developed and validated a new
      functionally-oriented outcome measure and propose that future clinical trials in
      prion disease should collect data compatible with this scale, to allow for
      combined and comparative analyses. Such approaches may be advantageous in orphan
      conditions, where single studies of feasible duration will often struggle to
      achieve statistical power.

PMID- 23550115
TI  - An Exploratory Analysis of Changes in Self-Regulation and Social Support Among
      Men and Women in Recovery.
AB  - The present study examined the association between changes in self-regulation and
      measures of general and specific social support that occurred across an 8 month
      interval among adults (n = 469: 317 men, 152 women; M age = 39.0 years) with
      histories of substance abuse. Participants resided in communal living,
      democratically governed, abstinent homes (n = 143) located across the United
      States. Participants' self-regulation scores, on average, increased over the 8
      month period and the self-regulation change scores were significantly related to
      general social support. In addition, self-regulation score changes were
      associated with the participant's social network's support for drinking where
      greater support for drinking was accompanied by larger self-regulation increases.
      These findings augment research on multi-factor support theories and changes in
      self-regulation.

PMID- 23550116
TI  - An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce.
AB  - We have generated an ultra-high-density genetic map for lettuce, an economically
      important member of the Compositae, consisting of 12,842 unigenes (13,943
      markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage
      groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array
      containing 6.4 million features representing 35,628 unigenes of Lactuca spp.
      Segregation of single-position polymorphisms was analyzed using 213 F7:8
      recombinant inbred lines that had been generated by crossing cultivated Lactuca
      sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of
      L. sativa The high level of replication of each allele in the recombinant inbred
      lines was exploited to identify single-position polymorphisms that were assigned
      to parental haplotypes. Marker information has been made available using GBrowse
      to facilitate access to the map. This map has been anchored to the previously
      published integrated map of lettuce providing candidate genes for multiple
      phenotypes. The high density of markers achieved in this ultradense map allowed
      syntenic studies between lettuce and Vitis vinifera as well as other plant
      species.

PMID- 23550117
TI  - ZRT1 Harbors an Excess of Nonsynonymous Polymorphism and Shows Evidence of
      Balancing Selection in Saccharomyces cerevisiae.
AB  - Estimates of the fraction of nucleotide substitutions driven by positive
      selection vary widely across different species. Accounting for different
      estimates of positive selection has been difficult, in part because selection on
      polymorphism within a species is known to obscure a signal of positive selection
      among species. While methods have been developed to control for the confounding
      effects of negative selection against deleterious polymorphism, the impact of
      balancing selection on estimates of positive selection has not been assessed. In
      Saccharomyces cerevisiae, there is no signal of positive selection within protein
      coding sequences as the ratio of nonsynonymous to synonymous polymorphism is
      higher than that of divergence. To investigate the impact of balancing selection
      on estimates of positive selection, we examined five genes with high rates of
      nonsynonymous polymorphism in S. cerevisiae relative to divergence from S.
      paradoxus One of the genes, the high-affinity zinc transporter ZRT1 showed an
      elevated rate of synonymous polymorphism indicative of balancing selection. The
      high rate of synonymous polymorphism coincided with nonsynonymous divergence
      among three haplotype groups, among which we found no detectable differences in
      ZRT1 function. Our results implicate balancing selection in one of five genes
      exhibiting a large excess of nonsynonymous polymorphism in yeast. We conclude
      that balancing selection is a potentially important factor in estimating the
      frequency of positive selection across the yeast genome.

PMID- 23550118
TI  - Influence of steroid hormone signaling on life span control by Caenorhabditis
      elegans insulin-like signaling.
AB  - Sterol-sensing nuclear receptors and insulin-like growth factor signaling play
      evolutionarily conserved roles in the control of aging. In the nematode
      Caenorhabditis elegans, bile acid-like steroid hormones known as dafachronic
      acids (DAs) influence longevity by binding to and regulating the activity of the
      conserved nuclear receptor DAF-12, and the insulin receptor (InsR) ortholog DAF-2
      controls life span by inhibiting the FoxO transcription factor DAF-16. How the
      DA/DAF-12 pathway interacts with DAF-2/InsR signaling to control life span is
      poorly understood. Here we specifically investigated the roles of liganded and
      unliganded DAF-12 in life span control in the context of reduced DAF-2/InsR
      signaling. In animals with reduced daf-2/InsR activity, mutations that either
      reduce DA biosynthesis or fully abrogate DAF-12 activity shorten life span,
      suggesting that liganded DAF-12 promotes longevity. In animals with reduced DAF
      2/InsR activity induced by daf-2/InsR RNAi, both liganded and unliganded DAF-12
      promote longevity. However, in daf-2/InsR mutants, liganded and unliganded DAF-12
      act in opposition to control life span. Thus, multiple DAF-12 activities
      influence life span in distinct ways in contexts of reduced DAF-2/InsR signaling.
      Our findings establish new roles for a conserved steroid signaling pathway in
      life span control and elucidate interactions among DA biosynthetic pathways, DAF
      12, and DAF-2/InsR signaling in aging.

PMID- 23550119
TI  - Linkage Disequilibrium Estimation of Effective Population Size with Immigrants
      from Divergent Populations: A Case Study on Spanish Mackerel (Scomberomorus
      commerson).
AB  - Estimates of genetic effective population size (Ne) using molecular markers are a
      potentially useful tool for the management of endangered through to commercial
      species. However, pitfalls are predicted when the effective size is large because
      estimates require large numbers of samples from wild populations for statistical
      validity. Our simulations showed that linkage disequilibrium estimates of Ne up
      to 10,000 with finite confidence limits can be achieved with sample sizes of
      approximately 5000. This number was deduced from empirical allele frequencies of
      seven polymorphic microsatellite loci in a commercially harvested fisheries
      species, the narrow-barred Spanish mackerel (Scomberomorus commerson). As
      expected, the smallest SD of Ne estimates occurred when low-frequency alleles
      were excluded. Additional simulations indicated that the linkage disequilibrium
      method was sensitive to small numbers of genotypes from cryptic species or
      conspecific immigrants. A correspondence analysis algorithm was developed to
      detect and remove outlier genotypes that could possibly be inadvertently sampled
      from cryptic species or nonbreeding immigrants from genetically separate
      populations. Simulations demonstrated the value of this approach in Spanish
      mackerel data. When putative immigrants were removed from the empirical data, 95%
      of the Ne estimates from jacknife resampling were greater than 24,000.

PMID- 23550120
TI  - Assembly of the Synaptonemal Complex Is a Highly Temperature-Sensitive Process
      That Is Supported by PGL-1 During Caenorhabditis elegans Meiosis.
AB  - Successful chromosome segregation during meiosis depends on the synaptonemal
      complex (SC), a structure that stabilizes pairing between aligned homologous
      chromosomes. Here we show that SC assembly is a temperature-sensitive process
      during Caenorhabditis elegans meiosis. Temperature sensitivity of SC assembly
      initially was revealed through identification of the germline-specific P-granule
      component PGL-1 as a factor promoting stable homolog pairing. Using an assay
      system that monitors homolog pairing in vivo, we showed that depletion of PGL-1
      at 25 degrees  disrupts homolog pairing. Analysis of homolog pairing at other
      chromosomal loci in a pgl-1-null mutant revealed a pairing defect similar to that
      observed in mutants lacking SC central region components. Furthermore, loss of
      pgl-1 function at temperatures >=25 degrees  results in severe impairment in
      loading of SC central region component SYP-1 onto chromosomes, resulting in
      formation of SYP-1 aggregates. SC assembly is also temperature sensitive in wild
      type worms, which exhibit similar SYP-1 loading defects and formation of SYP-1
      aggregates at temperatures >=26.5 degrees . Temperature shift analyses suggest
      that assembly of the SC is temperature sensitive, but maintenance of the SC is
      not. We suggest that the temperature sensitive (ts) nature of SC assembly may
      contribute to fitness and adaptation capacity in C. elegans by enabling meiotic
      disruption in response to environmental change, thereby increasing the production
      of male progeny available for outcrossing.

PMID- 23550121
TI  - Plastome Sequence Determination and Comparative Analysis for Members of the
      Lolium-Festuca Grass Species Complex.
AB  - Chloroplast genome sequences are of broad significance in plant biology, due to
      frequent use in molecular phylogenetics, comparative genomics, population
      genetics, and genetic modification studies. The present study used a second
      generation sequencing approach to determine and assemble the plastid genomes
      (plastomes) of four representatives from the agriculturally important Lolium
      Festuca species complex of pasture grasses (Lolium multiflorum, Festuca
      pratensis, Festuca altissima, and Festuca ovina). Total cellular DNA was
      extracted from either roots or leaves, was sequenced, and the output was filtered
      for plastome-related reads. A comparison between sources revealed fewer plastome
      related reads from root-derived template but an increase in incidental bacterium
      derived sequences. Plastome assembly and annotation indicated high levels of
      sequence identity and a conserved organization and gene content between species.
      However, frequent deletions within the F. ovina plastome appeared to contribute
      to a smaller plastid genome size. Comparative analysis with complete plastome
      sequences from other members of the Poaceae confirmed conservation of most grass
      specific features. Detailed analysis of the rbcL-psaI intergenic region, however,
      revealed a "hot-spot" of variation characterized by independent deletion events.
      The evolutionary implications of this observation are discussed. The complete
      plastome sequences are anticipated to provide the basis for potential organelle
      specific genetic modification of pasture grasses.

PMID- 23550122
TI  - Reproductive status alters transcriptomic response to infection in female
      Drosophila melanogaster.
AB  - Mating and consequent reproduction significantly reduce the ability of female
      Drosophila melanogaster to defend against systemic bacterial infection. The goal
      of the present study was to identify genes likely to inform the mechanism of this
      post-mating immunosuppression. We used microarrays to contrast genome-wide
      transcript levels in virgin vs. mated females before and after infection. Because
      the immunosuppressive effect of mating is contingent on the presence of a
      germline in females, we repeated the entire experiment by using female mutants
      that do not form a germline. We found that multiple genes involved in egg
      production show reduced expression in response to infection, and that this
      reduction is stronger in virgins than it is in mated females. In germline-less
      females, expression of egg-production genes was predictably low and not
      differentially affected by infection. We also identified several immune
      responsive genes that are differentially induced after infection in virgins vs.
      mated females. Immune genes affected by mating status and egg production genes
      altered by infection are candidates to inform the mechanism of the trade-off
      between mating and immune defense.

PMID- 23550124
TI  - Parents Without Partners: Drosophila as a Model for Understanding the Mechanisms
      and Evolution of Parthenogenesis.
AB  - Of 40 Drosophila species screened to date, a majority have shown some ability to
      at least initiate parthenogenetic development. In one case, Drosophila
      mangebeirai, natural populations are entirely female, making it the only obligate
      parthenogenetic species of Drosophila Only a few of the species that exhibit the
      ability to undergo early embryonic development of unfertilized eggs successfully
      respond to selection for parthenogenetic production of adult flies. Laboratory
      strains of parthenogenetic Drosophila mercatorum have been created by artificial
      selection on multiple occasions, but the proportion of eggs undergoing
      development to adulthood has never exceeded 8%. Selection produces gains in the
      number of unfertilized eggs undergoing early development, but the majority arrest
      at the embryonic or first larval instar stages. Four components to successful
      parthenogenesis include (1) a female's propensity to lay unfertilized eggs, (2)
      the ability of the eggs to restore diploidy, (3) the ability of the
      parthenogenetically produced diploid embryo to complete larval development and
      pupation, and (4) the existence of genetic variability within and among
      Drosophila species in the frequency of parthenogenesis suggests the existence of
      multiple steps in its evolution and offers a way to explore the genetics of this
      unusual reproductive strategy.

PMID- 23550123
TI  - A Whole Genome Screen for Minisatellite Stability Genes in Stationary-Phase Yeast
      Cells.
AB  - Repetitive elements comprise a significant portion of most eukaryotic genomes.
      Minisatellites, a type of repetitive element composed of repeat units 15-100 bp
      in length, are stable in actively dividing cells but change in composition during
      meiosis and in stationary-phase cells. Alterations within minisatellite tracts
      have been correlated with the onset of a variety of diseases, including diabetes
      mellitus, myoclonus epilepsy, and several types of cancer. However, little is
      known about the factors preventing minisatellite alterations. Previously, our
      laboratory developed a color segregation assay in which a minisatellite was
      inserted into the ADE2 gene in the yeast Saccharomyces cerevisiae to monitor
      alteration events. We demonstrated that minisatellite alterations that occur in
      stationary-phase cells give rise to a specific colony morphology phenotype known
      as blebbing. Here, we performed a modified version of the synthetic genetic array
      analysis to screen for mutants that produce a blebbing phenotype. Screens were
      conducted using two distinctly different minisatellite tracts: the ade2-min3
      construct consisting of three identical 20-bp repeats, and the ade2-h7.5
      construct, consisting of seven-and-a-half 28-bp variable repeats. Mutations in
      102 and 157 genes affect the stability of the ade2-min3 and ade2-h7.5 alleles,
      respectively. Only seven hits overlapped both screens, indicating that different
      factors regulate repeat stability depending upon minisatellite size and
      composition. Importantly, we demonstrate that mismatch repair influences the
      stability of the ade2-h7.5 allele, indicating that this type of DNA repair
      stabilizes complex minisatellites in stationary phase cells. Our work provides
      insight into the factors regulating minisatellite stability.

PMID- 23550125
TI  - Donor DNA Utilization During Gene Targeting with Zinc-Finger Nucleases.
AB  - Gene targeting is the term commonly applied to experimental gene replacement by
      homologous recombination (HR). This process is substantially stimulated by a
      double-strand break (DSB) in the genomic target. Zinc-finger nucleases (ZFNs) are
      targetable cleavage reagents that provide an effective means of introducing such
      a break in conjunction with delivery of a homologous donor DNA. In this study we
      explored several parameters of donor DNA structure during ZFN-mediated gene
      targeting in Drosophila melanogaster embryos, as follows. 1) We confirmed that HR
      outcomes are enhanced relative to the alternative nonhomologous end joining
      (NHEJ) repair pathway in flies lacking DNA ligase IV. 2) The minimum amount of
      homology needed to support efficient HR in fly embryos is between 200 and 500 bp.
      3) Conversion tracts are very broad in this system: donor sequences more than 3
      kb from the ZFN-induced break are found in the HR products at approximately 50%
      of the frequency of a marker at the break. 4) Deletions carried by the donor DNA
      are readily incorporated at the target. 5) While linear double-stranded DNAs are
      not effective as donors, single-stranded oligonucleotides are. These observations
      should enable better experimental design for gene targeting in Drosophila and
      help guide similar efforts in other systems.

PMID- 23550126
TI  - Distribution of long-range linkage disequilibrium and Tajima's D values in
      Scandinavian populations of Norway Spruce (Picea abies).
AB  - The site frequency spectrum of mutations (SFS) and linkage disequilibrium (LD)
      are the two major sources of information in population genetics studies. In this
      study we focus on the levels of LD and the SFS and on the effect of sample size
      on summary statistics in 10 Scandinavian populations of Norway spruce. We found
      that previous estimates of a low level of LD were highly influenced by both
      sampling strategy and the fact that data from multiple loci were analyzed
      jointly. Estimates of LD were in fact heterogeneous across loci and increased
      within individual populations compared with the estimate from the total data. The
      variation in levels of LD among populations most likely reflects different
      demographic histories, although we were unable to detect population structure by
      using standard approaches. As in previous studies, we also found that the SFS
      based test Tajima's D was highly sensitive to sample size, revealing that care
      should be taken to draw strong conclusions from this test when sample size is
      small. In conclusion, the results from this study are in line with recent studies
      in other conifers that have revealed a more complex and variable pattern of LD
      than earlier studies suggested and with studies in trees and humans that suggest
      that Tajima's D is sensitive to sample size. This has large consequences for the
      design of future association and population genetic studies in Norway spruce.

PMID- 23550127
TI  - A Functional Comparison of the 3xP3 Promoter by Recombinase-Mediated Cassette
      Exchange in Drosophila and a Tephritid Fly, Anastrepha suspensa.
AB  - Transposable elements are widely used as vectors for integrating transgenes into
      the genome of insects. However, the random nature of transposon vector
      integrations often results in mutations and makes transgene expression subject to
      variable genomic position effects. This makes reliable quantitative comparisons
      of different transgenes difficult and development of highly fit transgenic
      strains laborious. Tools for site-specific transgene targeting are essential for
      functional genomic comparisons and to develop the most advanced transgenic insect
      strains for applied use. Here we describe a recombinase-mediated cassette
      exchange gene targeting system based on Cre/loxP that is highly efficient in
      Drosophila, and for the first time in a non-drosophilid, the tephritid fly,
      Anastrepha suspensa This system allowed a comparison of the Drosophila
      constitutive polyubiquitin promoter and the artificial 3xP3 tissue-specific
      promoter in the same genomic context within each species, showing that the widely
      used 3xP3 promoter is apparently nonfunctional in the tephritid fly.

PMID- 23550128
TI  - A targeted genetic modifier screen links the SWI2/SNF2 protein domino to growth
      and autophagy genes in Drosophila melanogaster.
AB  - Targeted genetic studies can facilitate phenotypic analyses and provide important
      insights into development and other complex processes. The SWI2/SNF2 DNA
      dependent ATPase Domino (Dom) of Drosophila melanogaster, a component of the
      Tip60 acetyltransferase complex, has been associated with a wide spectrum of
      cellular processes at multiple developmental stages. These include hematopoiesis,
      cell proliferation, homeotic gene regulation, histone exchange during DNA repair,
      and Notch signaling. To explore the wider gene network associated with Dom
      action, we used RNAi directed against domino (dom) to mediate loss-of-function at
      the wing margin, a tissue that is readily scored for phenotypic changes. Dom RNAi
      driven through GAL4-UAS elicited dominant wing nicking that responded
      phenotypically to the dose of dom and other loci known to function with dom. We
      screened for phenotypic modifiers of this wing phenotype among 2500
      transpositions of the EP P element and found both enhancers and suppressors.
      Several classes of modifier were obtained, including those encoding transcription
      factors, RNA regulatory proteins, and factors that regulate cell growth,
      proliferation and autophagy, a lysosomal degradation pathway that affects cell
      growth under conditions of starvation and stress. Our analysis is consistent with
      prior studies, suggesting that Dom acts pleiotropically as a positive effector of
      Notch signaling and a repressor of proliferation. This genetic system should
      facilitate screens for additional loci associated with Dom function, and
      complement biochemical approaches to their regulatory activity.

PMID- 23550129
TI  - Genome-Wide Detection of Gene Coexpression Domains Showing Linkage to Regions
      Enriched with Polymorphic Retrotransposons in Recombinant Inbred Mouse Strains.
AB  - Although gene coexpression domains have been reported in most eukaryotic
      organisms, data available to date suggest that coexpression rarely concerns more
      than doublets or triplets of adjacent genes in mammals. Using expression data
      from hearts of mice from the panel of AxB/BxA recombinant inbred mice, we
      detected (according to window sizes) 42-53 loci linked to the expression levels
      of clusters of three or more neighboring genes. These loci thus formed "cis
      expression quantitative trait loci (eQTL) clusters" because their position
      matched that of the genes whose expression was linked to the loci. Compared with
      matching control regions, genes contained within cis-eQTL clusters showed much
      greater levels of coexpression. Corresponding regions showed: (1) a greater
      abundance of polymorphic elements (mostly short interspersed element
      retrotransposons), and (2) significant enrichment for the motifs of binding sites
      for various transcription factors, with binding sites for the chromatin
      organizing CCCTC-binding factor showing the greatest levels of enrichment in
      polymorphic short interspersed elements. Similar cis-eQTL clusters also were
      detected when we used data obtained with several tissues from BxD recombinant
      inbred mice. In addition to strengthening the evidence for gene expression
      domains in mammalian genomes, our data suggest a possible mechanism whereby
      noncoding polymorphisms could affect the coordinate expression of several
      neighboring genes.

PMID- 23550130
TI  - Activation-Induced Cytidine Deaminase Does Not Impact Murine Meiotic
      Recombination.
AB  - Activation-induced cytidine deaminase (AID) was first described as the triggering
      enzyme of the B-cell-specific reactions that edit the immunoglobulin genes,
      namely somatic hypermutation, gene conversion, and class switch recombination.
      Over the years, AID was also detected in cells other than lymphocytes, and it has
      been assigned additional roles in the innate defense against transforming
      retroviruses, in retrotransposition restriction and in DNA demethylation.
      Notably, AID expression was found in germline tissues, and in heterologous
      systems it can induce the double-strand breaks required for the initiation of
      meiotic recombination and proper gamete formation. However, because AID-deficient
      mice are fully fertile, the molecule is not essential for meiosis. Thus, the
      remaining question that we addressed here is whether AID influences the frequency
      of meiotic recombination in mice. We measured the recombination events in the
      meiosis of male and female mice F1 hybrids of C57BL/6J and BALB/c, in Aicda+/+
      and Aicda-/- background by using a panel of single-nucleotide polymorphisms that
      distinguishes C57BL/6J from BALB/c genome across the 19 autosomes. In agreement
      with the literature, we found that the frequency of recombination in the female
      germline was greater than in male germline, both in the Aicda+/+ and Aicda-/-
      backgrounds. No statistical difference was found in the average recombination
      events between Aicda+/+ and Aidca-/- animals, either in females or males. In
      addition, the recombination frequencies between single-nucleotide polymorphisms
      flanking the immunoglobulin heavy and immunoglobulin kappa loci was also not
      different. We conclude that AID has a minor impact, if any, on the overall
      frequency of meiotic recombination.

PMID- 23550131
TI  - Trans-Lesion DNA Polymerases May Be Involved in Yeast Meiosis.
AB  - Trans-lesion DNA polymerases (TLSPs) enable bypass of DNA lesions during
      replication and are also induced under stress conditions. Being only weakly
      dependent on their template during replication, TLSPs introduce mutations into
      DNA. The low processivity of these enzymes ensures that they fall off their
      template after a few bases are synthesized and are then replaced by the more
      accurate replicative polymerase. We find that the three TLSPs of budding yeast
      Saccharomyces cerevisiae Rev1, PolZeta (Rev3 and Rev7), and Rad30 are induced
      during meiosis at a time when DNA double-strand breaks (DSBs) are formed and
      homologous chromosomes recombine. Strains deleted for one or any combination of
      the three TLSPs undergo normal meiosis. However, in the triple-deletion mutant,
      there is a reduction in both allelic and ectopic recombination. We suggest that
      trans-lesion polymerases are involved in the processing of meiotic double-strand
      breaks that lead to mutations. In support of this notion, we report significant
      yeast two-hybrid (Y2H) associations in meiosis-arrested cells between the TLSPs
      and DSB proteins Rev1-Spo11, Rev1-Mei4, and Rev7-Rec114, as well as between Rev1
      and Rad30 We suggest that the involvement of TLSPs in processing of meiotic DSBs
      could be responsible for the considerably higher frequency of mutations reported
      during meiosis compared with that found in mitotically dividing cells, and
      therefore may contribute to faster evolutionary divergence than previously
      assumed.

PMID- 23550132
TI  - Functional Annotation and Comparative Analysis of a Zygopteran Transcriptome.
AB  - In this paper we present a de novo assembly of the transcriptome of the damselfly
      (Enallagma hageni) through the use of 454 pyrosequencing. E. hageni is a member
      of the suborder Zygoptera, in the order Odonata, and Odonata organisms form the
      basal lineage of the winged insects (Pterygota). To date, sequence data used in
      phylogenetic analysis of Enallagma species have been derived from either
      mitochondrial DNA or ribosomal nuclear DNA. This Enallagma transcriptome
      contained 31,661 contigs that were assembled and translated into 14,813
      individual open reading frames. Using these data, we constructed an extensive
      dataset of 634 orthologous nuclear protein-encoding genes across 11 species of
      Arthropoda and used Bayesian techniques to elucidate the position of Enallagma in
      the arthropod phylogenetic tree. Additionally, we demonstrated that the Enallagma
      transcriptome contains 169 genes that are evolving at rates that differ relative
      to those of the rest of the transcriptome (29 accelerated and 140 decreased),
      and, through multiple Gene Ontology searches and clustering methods, we present
      the first functional annotation of any palaeopteran's transcriptome in the
      literature.

PMID- 23550133
TI  - Comparative Genomics of Serial Isolates of Cryptococcus neoformans Reveals Gene
      Associated With Carbon Utilization and Virulence.
AB  - The opportunistic fungal pathogen Cryptococcus neoformans is a leading cause of
      mortality among the human immunodeficiency virus/acquired immunodeficiency
      syndrome population and is known for frequently causing life-threatening
      relapses. To investigate the potential contribution of in-host microevolution to
      persistence and relapse, we have analyzed two serial isolates obtained from a
      patient with acquired immunodeficiency syndrome who suffered an initial and
      relapse episode of cryptococcal meningoencephalitis. Despite being identical by
      multilocus sequence typing, the isolates differ phenotypically, exhibiting
      changes in key virulence factors, nutrient acquisition, metabolic profiles, and
      the ability to disseminate in an animal model. Whole-genome sequencing uncovered
      a clonal relationship, with only a few unique differences. Of these, two key
      changes are expected to explain the phenotypic differences observed in the
      relapse isolate: loss of a predicted AT-rich interaction domain protein and
      changes in copy number of the left and right arms of chromosome 12. Gene deletion
      of the predicted transcriptional regulator produced changes in melanin, capsule,
      carbon source use, and dissemination in the host, consistent with the phenotype
      of the relapse isolate. In addition, the deletion mutant displayed altered
      virulence in the murine model. The observed differences suggest the relapse
      isolate evolved subsequent to penetration of the central nervous system and may
      have gained dominance following the administration of antifungal therapy. These
      data reveal the first molecular insights into how the Cryptococcus neoformans
      genome changes during infection of humans and the manner in which microevolution
      progresses in this deadly fungal pathogen.

PMID- 23550134
TI  - Inferring gene function and network organization in Drosophila signaling by
      combined analysis of pleiotropy and epistasis.
AB  - High-throughput genetic interaction screens have enabled functional genomics on a
      network scale. Groups of cofunctional genes commonly exhibit similar interaction
      patterns across a large network, leading to novel functional inferences for a
      minority of previously uncharacterized genes within a group. However, such
      analyses are often unsuited to cases with a few relevant gene variants or sparse
      annotation. Here we describe an alternative analysis of cell growth signaling
      using a computational strategy that integrates patterns of pleiotropy and
      epistasis to infer how gene knockdowns enhance or suppress the effects of other
      knockdowns. We analyzed the interaction network for RNAi knockdowns of a set of
      93 incompletely annotated genes in a Drosophila melanogaster model of cellular
      signaling. We inferred novel functional relationships between genes by modeling
      genetic interactions in terms of knockdown-to-knockdown influences. The method
      simultaneously analyzes the effects of partially pleiotropic genes on multiple
      quantitative phenotypes to infer a consistent model of each genetic interaction.
      From these models we proposed novel candidate Ras inhibitors and their Ras
      signaling interaction partners, and each of these hypotheses can be inferred
      independent of network-wide patterns. At the same time, the network-scale
      interaction patterns consistently mapped pathway organization. The analysis
      therefore assigns functional relevance to individual genetic interactions while
      also revealing global genetic architecture.

PMID- 23550136
TI  - The genomic and transcriptomic landscape of a HeLa cell line.
AB  - HeLa is the most widely used model cell line for studying human cellular and
      molecular biology. To date, no genomic reference for this cell line has been
      released, and experiments have relied on the human reference genome. Effective
      design and interpretation of molecular genetic studies performed using HeLa cells
      require accurate genomic information. Here we present a detailed genomic and
      transcriptomic characterization of a HeLa cell line. We performed DNA and RNA
      sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and
      gene expression profile. Segmentation of the genome according to copy number
      revealed a remarkably high level of aneuploidy and numerous large structural
      variants at unprecedented resolution. Some of the extensive genomic
      rearrangements are indicative of catastrophic chromosome shattering, known as
      chromothripsis. Our analysis of the HeLa gene expression profile revealed that
      several pathways, including cell cycle and DNA repair, exhibit significantly
      different expression patterns from those in normal human tissues. Our results
      provide the first detailed account of genomic variants in the HeLa genome,
      yielding insight into their impact on gene expression and cellular function as
      well as their origins. This study underscores the importance of accounting for
      the strikingly aberrant characteristics of HeLa cells when designing and
      interpreting experiments, and has implications for the use of HeLa as a model of
      human biology. 

PMID- 23550137
TI  - Physical and Genetic Interactions Between Uls1 and the Slx5-Slx8 SUMO-Targeted
      Ubiquitin Ligase.
AB  - The Slx5-Slx8 complex is a ubiquitin ligase that preferentially ubiquitylates
      SUMOylated substrates, targeting them for proteolysis. Mutations in SLX5, SLX8,
      and other SUMO pathway genes were previously identified in our laboratory as
      genomic suppressors of a point mutation (mot1-301) in the transcriptional
      regulator MOT1 To further understand the links between the SUMO and ubiquitin
      pathways, a screen was performed for high-copy suppressors of mot1-301, yielding
      three genes (MOT3, MIT1, and ULS1). MOT3 and MIT1 have characteristics of prions,
      and ULS1 is believed to encode another SUMO-targeted ubiquitin ligase (STUbL)
      that functionally overlaps with Slx5-Slx8. Here we focus on ULS1, obtaining
      results suggesting that the relationship between ULS1 and SLX5 is more complex
      than expected. Uls1 interacted with Slx5 physically in to yeast two-hybrid and co
      immunoprecipitation assays, a uls1 mutation that blocked the interaction between
      Uls1 and Slx5 interfered with ULS1 function, and genetic analyses indicated an
      antagonistic relationship between ULS1 and SLX5 Combined, our results challenge
      the assumption that Uls1 and Slx5 are simply partially overlapping STUbLs and
      begin to illuminate a regulatory relationship between these two proteins.

PMID- 23550138
TI  - The Biotinidase Gene Variants Registry: A Paradigm Public Database.
AB  - The BTD gene codes for production of biotinidase, the enzyme responsible for
      helping the body reuse and recycle the biotin found in foods. Biotinidase
      deficiency is an autosomal recessively inherited disorder resulting in the
      inability to recycle the vitamin biotin and affects approximately 1 in 60,000
      newborns. If untreated, the depletion of intracellular biotin leads to impaired
      activities of the biotin-dependent carboxylases and can result in cutaneous and
      neurological abnormalities in individuals with the disorder. Mutations in the
      biotinidase gene (BTD) alter enzymatic function. To date, more than 165 mutations
      in BTD have been reported. Our group has developed a database that characterizes
      the known mutations and sequence variants in BTD
      (http://arup.utah.edu/database/BTD/BTD_welcome.php). All sequence variants have
      been verified for their positions within the BTD gene and designated according to
      standard nomenclature suggested by Human Genome Variation Society (HGVS). In
      addition, we describe the change in the protein, indicate whether the variant is
      a known or likely mutation vs. a benign polymorphism, and include the reference
      that first described the alteration. We also indicate whether the alteration is
      known to be clinically pathological based on an observation of a known
      symptomatic individual or predicted to be pathological based on enzymatic
      activity or putative disruption of the protein structure. We incorporated the
      published phenotype to help establish genotype-phenotype correlations and
      facilitate this process for those performing mutation analysis and/or
      interpreting results. Other features of this database include disease
      information, relevant links about biotinidase deficiency, reference sequences,
      ability to query by various criteria, and the process for submitting novel
      variations. This database is free to the public and will be updated quarterly.
      This database is a paradigm for formulating databases for other inherited
      metabolic disorders.

PMID- 23550135
TI  - Population structure in a comprehensive genomic data set on human microsatellite
      variation.
AB  - Over the past two decades, microsatellite genotypes have provided the data for
      landmark studies of human population-genetic variation. However, the various
      microsatellite data sets have been prepared with different procedures and sets of
      markers, so that it has been difficult to synthesize available data for a
      comprehensive analysis. Here, we combine eight human population-genetic data sets
      at the 645 microsatellite loci they share in common, accounting for procedural
      differences in the production of the different data sets, to assemble a single
      data set containing 5795 individuals from 267 worldwide populations. We perform a
      systematic analysis of genetic relatedness, detecting 240 intra-population and 92
      inter-population pairs of previously unidentified close relatives and proposing
      standardized subsets of unrelated individuals for use in future studies. We then
      augment the human data with a data set of 84 chimpanzees at the 246 loci they
      share in common with the human samples. Multidimensional scaling and neighbor
      joining analyses of these data sets offer new insights into the structure of
      human populations and enable a comparison of genetic variation patterns in
      chimpanzees with those in humans. Our combined data sets are the largest of their
      kind reported to date and provide a resource for use in human population-genetic
      studies.

PMID- 23550140
TI  - Genetic Basis of Ammonium Toxicity Resistance in a Sake Strain of Yeast: A
      Mendelian Case.
AB  - High concentrations of ammonium at physiological concentrations of potassium are
      toxic for the standard laboratory strain of Saccharomyces cerevisiae In the
      original description of this metabolic phenotype, we focused on the standard
      laboratory strains of Saccharomyces In this study, we screened a large collection
      of S. cerevisiae natural isolates and identified one strain that is resistant to
      high concentrations of ammonium. This strain, K12, was isolated in sake
      breweries. When the K12 strain was crossed to the standard laboratory strain
      (FY4), the resulting tetrads displayed 2:2 segregation of the resistance
      phenotype, suggesting a single gene trait. Using a bulk segregant analysis
      strategy, we mapped this trait to a 150-kb region on chromosome X containing the
      TRK1 gene. This gene encodes a transporter required for high-affinity potassium
      transport in S. cerevisiae Data from reciprocal hemizygosity experiments with
      TRK1 deletion strains in K12 and BY backgrounds, as well as analysis of the
      deletion of this gene in the K12 strain, demonstrate that the K12 allele of TRK1
      is responsible for ammonium toxicity resistance. Furthermore, we determined the
      minimal amount of potassium required for both the K12 and laboratory strain
      needed for growth. These results demonstrate that the gene encoded by the K12
      allele of TRK1 has a greater affinity for potassium than the standard allele of
      TRK1 found in Saccharomyces strains. We hypothesize that this greater-affinity
      allele of the potassium transporter reduces the flux of ammonium into the yeast
      cells under conditions of ammonium toxicity. These findings further refine our
      understanding of ammonium toxicity in yeast and provide an example of using
      natural variation to understand cellular processes.

PMID- 23550139
TI  - Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked
      SOD1 in Drosophila.
AB  - Amyotrophic lateral sclerosis (ALS) generally is a late-onset neurodegenerative
      disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene account for
      approximately 20% of familial ALS and 2% of all ALS cases. Although a number of
      hypotheses have been proposed to explain mutant SOD1 toxicity, the molecular
      mechanisms of the disease remain unclear. SOD1-linked ALS is thought to function
      in a non-cell-autonomous manner such that motoneurons are critical for the onset,
      and glia contribute to progression of the disease. Recently, it has been shown in
      Drosophila melanogaster that expression of human SOD1 in a subset of neuronal
      cells causes synaptic transmission defects, modified motor function, and altered
      sensitivity to compounds that induce oxidative stress. Here we used the Gal4-UAS
      (Upstream Activation Sequence) system to further characterize flies expressing
      wild-type Drosophila SOD1 (dSOD1) and the mutant human SOD1G85R (G85R) allele in
      motoneurons and glia. Cell-specific expression of both dSOD1 and G85R was found
      to influence lifespan, affect sensitivity to hydrogen peroxide, and alter lipid
      peroxidation levels. To better understand the genetic consequences of G85R
      expression in motoneurons and glia, we conducted microarray analysis of both
      young flies (5 days old) and old flies (45 days old) expressing G85R selectively
      in motoneurons or glia and concurrently in motoneurons and glia. Results from
      this microarray experiment identified candidate genes for further investigation
      and may help elucidate the individual and combined contributions of motoneurons
      and glia in ALS.

PMID- 23550141
TI  - Involvement of MLPK Pathway in Intraspecies Unilateral Incompatibility Regulated
      by a Single Locus With Stigma and Pollen Factors.
AB  - Plants have evolved many systems to prevent undesirable fertilization. Among
      these, incompatibility is a well-organized system in which pollen germination or
      pollen tube growth is inhibited in pistils. We previously found that a novel one
      way pollen-stigma incompatibility response [unilateral incompatibility (UI)]
      occurred between two self-incompatible Brassica rapa plants, a Turkish line, and
      a Japanese cultivated hybrid variety, "Osome." Pollen from the Turkish line is
      rejected on the stigma of the Osome line, but the reverse cross is compatible;
      such a UI phenotype closely resembles self-incompatibility (SI). The pollen
      factor of this UI has been genetically explained by a single locus which is
      different from the S-locus. In this study, we performed further genetic analyses
      of this intraspecies UI and showed that the stigma factor was also controlled by
      a single locus, and we named the loci corresponding to the stigma and pollen
      factors of the intraspecies UI, stigmatic unilateral incompatibility (SUI), and
      pollen unilateral incompatibility (PUI) loci, respectively. Interestingly,
      segregation analyses of SUI and PUI indicated that they are closely linked to
      each other and behave as a single unit. To investigate the effect of an SI
      related gene, MLPK in this UI, we produced segregation lines for SUI and mlpk A
      distorted segregation ratio of SUI phenotype in an mlpk background indicated
      involvement of MLPK in SUI, suggesting the existence of an MLPK-dependent novel
      pollen-stigma recognition mechanism.

PMID- 23550142
TI  - A high-fidelity cell lineage tracing method for obtaining systematic
      spatiotemporal gene expression patterns in Caenorhabditis elegans.
AB  - Advances in microscopy and fluorescent reporters have allowed us to detect the
      onset of gene expression on a cell-by-cell basis in a systemic fashion. This
      information, however, is often encoded in large repositories of images, and
      developing ways to extract this spatiotemporal expression data is a difficult
      problem that often uses complex domain-specific methods for each individual data
      set. We present a more unified approach that incorporates general previous
      information into a hierarchical probabilistic model to extract spatiotemporal
      gene expression from 4D confocal microscopy images of developing Caenorhabditis
      elegans embryos. This approach reduces the overall error rate of our automated
      lineage tracing pipeline by 3.8-fold, allowing us to routinely follow the C.
      elegans lineage to later stages of development, where individual neuronal
      subspecification becomes apparent. Unlike previous methods that often use custom
      approaches that are organism specific, our method uses generalized linear models
      and extensions of standard reversible jump Markov chain Monte Carlo methods that
      can be readily extended to other organisms for a variety of biological inference
      problems relating to cell fate specification. This modeling approach is flexible
      and provides tractable avenues for incorporating additional previous information
      into the model for similar difficult high-fidelity/low error tolerance image
      analysis problems for systematically applied genomic experiments.

PMID- 23550143
TI  - PRICE: software for the targeted assembly of components of (Meta) genomic
      sequence data.
AB  - Low-cost DNA sequencing technologies have expanded the role for direct nucleic
      acid sequencing in the analysis of genomes, transcriptomes, and the metagenomes
      of whole ecosystems. Human and machine comprehension of such large datasets can
      be simplified via synthesis of sequence fragments into long, contiguous blocks of
      sequence (contigs), but most of the progress in the field of assembly has focused
      on genomes in isolation rather than metagenomes. Here, we present software for
      paired-read iterative contig extension (PRICE), a strategy for focused assembly
      of particular nucleic acid species using complex metagenomic data as input. We
      describe the assembly strategy implemented by PRICE and provide examples of its
      application to the sequence of particular genes, transcripts, and virus genomes
      from complex multicomponent datasets, including an assembly of the BCBL-1 strain
      of Kaposi's sarcoma-associated herpesvirus. PRICE is open-source and available
      for free download (derisilab.ucsf.edu/software/price/ or
      sourceforge.net/projects/pricedenovo/).

PMID- 23550145
TI  - Viral evolution: Primordial cellular origins and late adaptation to parasitism.
AB  - Explaining the origin of viruses remains an important challenge for evolutionary
      biology. Previous explanatory frameworks described viruses as founders of
      cellular life, as parasitic reductive products of ancient cellular organisms or
      as escapees of modern genomes. Each of these frameworks endow viruses with
      distinct molecular, cellular, dynamic and emergent properties that carry broad
      and important implications for many disciplines, including biology, ecology and
      epidemiology. In a recent genome-wide structural phylogenomic analysis, we have
      shown that large-to-medium-sized viruses coevolved with cellular ancestors and
      have chosen the evolutionary reductive route. Here we interpret these results and
      provide a parsimonious hypothesis for the origin of viruses that is supported by
      molecular data and objective evolutionary bioinformatic approaches. Results
      suggest two important phases in the evolution of viruses: (1) origin from
      primordial cells and coexistence with cellular ancestors, and (2) prolonged
      pressure of genome reduction and relatively late adaptation to the parasitic
      lifestyle once virions and diversified cellular life took over the planet. Under
      this evolutionary model, new viral lineages can evolve from existing cellular
      parasites and enhance the diversity of the world's virosphere.

PMID- 23550144
TI  - Genome-wide association analysis of avian resistance to Campylobacter jejuni
      colonization identifies risk locus spanning the CDH13 gene.
AB  - The enteropathogen Campylobacter jejuni is a major worldwide health and economic
      burden, being one of the leading causes of bacterial gastroenteritis and commonly
      linked to postinfectious onset of autoimmune disease. Chickens are a major vector
      for human infection and even though variation in avian colonization level is
      heritable, no previous studies have identified regions of the genome associated
      with colonization resistance. We performed a genome-wide association study of
      resistance to C. jejuni colonization in the avian intestine by controlling for
      population structure, which revealed a risk locus with genome-wide significance
      spanning the T-cadherin (CDH13) gene. A second possible risk locus was also
      identified close to calmodulin (CALM1), a calcium-activated modulator of cadherin
      function. In addition, gene expression analysis of mRNA sequencing profiles
      revealed that the relative expression of the two genes is significantly
      associated with colonization resistance. Functional studies have previously
      demonstrated involvement of cadherins and calmodulin in C. jejuni intracellular
      invasion and colonization of human intestinal epithelial cells in vitro.
      Consistent with this finding, our analysis reveals that variation surrounding
      these genes is associated with avian colonization resistance in vivo and
      highlights their potential as possible targets for control of the bacterium in
      avian and human populations.

PMID- 23550146
TI  - Effect of patient-optimized doses of tamsulosin on erectile function in men with
      erectile dysfunction and lower urinary tract symptoms.
AB  - PURPOSE: To investigate the relationship of improvement in erectile function (EF)
      with improvement in lower urinary tract symptoms (LUTS) and to assess the
      contribution of tamsulosin dose to the improvement of EF apart from the indirect
      influence of LUTS improvement in men with LUTS and erectile dysfunction (ED).
      MATERIALS AND METHODS: Fifty patients received tamsulosin 0.2 mg/d for the first
      4 weeks and were subsequently divided into two groups by patient-reported
      outcomes. Nonescalators were maintained starting dose and escalators increased to
      0.4 mg for the remaining 8 weeks. International Prostatic Symptom Score (IPSS)
      and International Index of Erectile Function (IIEF-5), and underwent uroflowmetry
      were evaluated at baseline, and weeks 4 and 12. RESULTS: LUTS parameters were
      significantly improved in both groups but insignificant between the 2 groups. The
      degree of the improvement in the total IPSS and in the voiding, storage, and
      quality of life (QoL) subscores were significantly correlated with the degree of
      the improvement in EF; this was especially prominent in patients successfully
      treated LUTS. The escalators experienced a significantly greater increase in IIEF
      5 scores than did the nonescalators (3.3 vs. 1.5). CONCLUSIONS: Dose escalation
      provided similar LUTS improvement in patients with refractory to starting dose.
      The improvements of LUTS were correlated with the improvement of EF. The increase
      in the IIEF-5 score was significantly higher in escalators. These findings imply
      that tamsulosin may contribute to the improvement in EF through the improvement
      of LUTS and QoL and direct relaxation of the corpus cavernosum in a dose
      dependent fashion.

PMID- 23550147
TI  - The basic principles of chimeric antigen receptor design.
AB  - Chimeric antigen receptors (CAR) are recombinant receptors that provide both
      antigen-binding and T-cell-activating functions. A multitude of CARs has been
      reported over the past decade, targeting an array of cell surface tumor antigens.
      Their biologic functions have dramatically changed following the introduction of
      tripartite receptors comprising a costimulatory domain, termed second-generation
      CARs. These have recently shown clinical benefit in patients treated with CD19
      targeted autologous T cells. CARs may be combined with costimulatory ligands,
      chimeric costimulatory receptors, or cytokines to further enhance T-cell potency,
      specificity, and safety. CARs represent a new class of drugs with exciting
      potential for cancer immunotherapy. SIGNIFICANCE: CARs are a new class of drugs
      with great potential for cancer immunotherapy. Upon their expression in T
      lymphocytes, CARs direct potent, targeted immune responses that have recently
      shown encouraging clinical outcomes in a subset of patients with B-cell
      malignancies. This review focuses on the design of CARs, including the
      requirements for optimal antigen recognition and different modalities to provide
      costimulatory support to targeted T cells, which include the use of second- and
      third generation CARs, costimulatory ligands, chimeric costimulatory receptors,
      and cytokines.

PMID- 23550148
TI  - Succinate dehydrogenase mutation underlies global epigenomic divergence in
      gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal
      transduction kinases such as KIT, or, alternatively, manifest loss-of-function
      defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component
      of the Krebs cycle and electron transport chain. We have uncovered a striking
      divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24)
      versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K
      methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed
      an order of magnitude greater genomic hypermethylation relative to SDH-deficient
      GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic
      divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n =
      29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH
      mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle
      defective tumor type, revealed comparable measures of global hypo- and
      hypermethylation. These data expose a vital connection between succinate
      metabolism and genomic DNA methylation during tumorigenesis, and generally
      implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.

PMID- 23550150
TI  - Regulation of Mac-2BP secretion is mediated by its N-glycan binding to ERGIC-53.
AB  - The leguminous-type (L-type) lectin ER-Golgi intermediate compartment (ERGIC)-53,
      a homo-oligomeric endoplasmic reticulum (ER)-Golgi recycling protein, functions
      as a transport receptor for newly synthesized glycoproteins in the early
      secretory pathway. Although a limited subset of cargo glycoproteins transported
      by ERGIC-53, such as the coagulation factors V and VIII, cathepsin C and Z and
      alpha1-antitrypsin, has been identified, the exact role of the N-glycan binding
      of ERGIC-53 in the transport of secretory glycoproteins for ER exit has yet to be
      clarified. By screening a cDNA library isolated from HepG2 cells via a green
      fluorescent protein fragment complementation assay, we assessed several candidate
      luminal ERGIC-53-interacting partners and identified Mac-2 binding protein (Mac
      2BP) as a novel ERGIC-53-transported cargo glycoprotein. Using an N-glycan
      binding-deficient mutant of ERGIC-53 (N156A) or treatment with N-glycosylation
      processing inhibitors, as well as the introduction of the ER-mis-targeting mutant
      (KKAA), we demonstrated that the high-mannose-type N-glycan binding of ERGIC-53
      contributes to its interaction with Mac-2BP, which is essential for the ERGIC-53
      mediated ER-Golgi transport of nascent proteins during early secretion.
      Furthermore, we also provide evidence that MCFD2 is involved in the secretion of
      Mac-2BP. These observations reveal a distinct role for the N-glycan binding of
      ERGIC-53 in the receptor-mediated ER exit of newly synthesized Mac-2BP in the
      early secretion pathway.

PMID- 23550149
TI  - Lack of galectin-1 or galectin-3 alters B cell deletion and anergy in an
      autoantibody transgene model.
AB  - Members of the galectin family of proteins have been shown to regulate the
      development and the function of immune cells. We previously identified the
      increased expression of galectin-1 and galectin-3 mRNA and protein in anergic B
      cells relative to their naive counterparts. To investigate the role of these
      galectins in maintaining B cell tolerance, we crossed mice deficient in galectin
      1 or galectin-3 with mice bearing a lupus autoantigen-binding transgenic (Tg) B
      cell receptor, using a model with a well-characterized B cell tolerance phenotype
      of deletion, receptor editing and anergy. Here, we present data showing that the
      global knockout of galectin-1 or galectin-3 yields subtle alterations in B cell
      fate in autoantibody Tg mice. The absence of galectin-3 leads to a significant
      increase in the number of Tg spleen B cells, with the recovery of anti-laminin
      antibodies from a subset of mice. The B cell number increases further in antibody
      Tg mice with the dual deficiency of both galectin-1 and galectin-3. Isolated
      galectin-1 deficiency significantly enhances the proliferation of Tg B cells in
      response to lipopolysaccharide stimulation. These findings add to the growing
      body of evidence indicating a role for the various galectin family members, and
      for galectins 1 and 3 in particular, in the regulation of autoimmunity.

PMID- 23550151
TI  - Association of high blood pressure with heart rate variability in children.
AB  - OBJECTIVE: To determine the association between heart rate variability (HRV) and
      hypertension in Chinese children. METHODS: The study was conducted in First
      Hospital of Jilin University, China. A total of 101 children were recruited in
      this study. They were divided into a high systolic blood pressure (SBP) group (HS
      group) and normal SBP group (NS group) according to the SBP levels. In the second
      set of experiments, the children were divided into a high diastolic blood
      pressure (DBP) group (HD group) and normal DBP group (ND group) according to the
      DBP levels. HRV measurements were performed, and the time domain and power
      spectrum values were calculated. FINDINGS: The differences of low frequency
      (LF)/high frequency (HF) ratio, HF, and standard deviation of normal-to-normal RR
      intervals (SDNN) between daytime and nighttime were obviously abolished in HS and
      HD groups. The HS group displayed significantly lower values of HRV over a 24 h
      period compared to the NS group (SDNN, standard deviation of the averaged normal
      to-normal RR intervals [SDANN], Triangle Index, root mean square successive
      difference [RMSSD], total power [TP], ultra-LF [ULF], and HF). Only the Triangle
      Index in the HD group was lower than that in ND group. CONCLUSION: We provide
      evidence that HRV is reduced and the circadian rhythm of HRV is weakened in
      hypertensive children, and hypothesize that a reduced HRV is a potential
      pathophysiological mechanism linking childhood hypertension and adulthood
      cardiovascular diseases.

PMID- 23550152
TI  - Chemoprevention of lung squamous cell carcinoma by ginseng.
AB  - Ginseng has been used as a medicinal herb to maintain physical vitality for
      thousands of years, and it has also been shown to be a nonorgan-specific cancer
      preventive agent by several epidemiologic studies. However, the chemopreventive
      effects of Korea white ginseng (KWG) in lung squamous cell carcinoma (SCC) have
      not been tested. In this study, we investigated the chemopreventive activity of
      KWG in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to
      induce lung tumors in female Swiss mice, and KWG was given orally. KWG
      significantly reduced the percentage of lung SCCs from 26.5% in the control group
      to 9.1% in the KWG group and in the meantime, increased the percentage of normal
      bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell
      lung tumor area from an average of 9.4% in control group to 1.5% in the KWG
      group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung
      tumor inhibitory effects of KWG were partly through inhibition of proliferation.
      High-performance liquid chromatography/mass spectrometry identified 10
      ginsenosides from KWG extracts, Rb1 and Rd being the most abundant as detected in
      mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by
      inhibition of activator protein (AP-1), as showed by in vitro study conducted on
      AP-1/NF-kappaB-dependent mouse non-small cell lung carcinoma cell lines. Western
      blotting of lung tissues also indicated that NTCU upregulated AP-1 through
      phosphorylation of c-jun-NH2-kinase, which was downregulated by KWG in
      concurrence with its chemoprevention function. These results suggest that KWG
      could be a potential chemopreventive agent for lung SCC.

PMID- 23550154
TI  - A closer look at supercritical water.

PMID- 23550153
TI  - Combination of intermittent calorie restriction and eicosapentaenoic acid for
      inhibition of mammary tumors.
AB  - There are a number of dietary interventions capable of inhibiting mammary
      tumorigenesis; however, the effectiveness of dietary combinations is largely
      unexplored. Here, we combined 2 interventions previously shown individually to
      inhibit mammary tumor development. The first was the use of the omega-3 fatty
      acid, eicosapentaenoic acid (EPA), and the second was the implementation of
      calorie restriction. MMTV-Her2/neu mice were used as a model for human breast
      cancers, which overexpress Her2/neu. Six groups of mice were enrolled. Half were
      fed a control (Con) diet with 10.1% fat calories from soy oil, whereas the other
      half consumed a diet with 72% fat calories from EPA. Within each diet, mice were
      further divided into ad libitum (AL), chronic calorie-restricted (CCR), or
      intermittent calorie-restricted (ICR) groups. Mammary tumor incidence was lowest
      in ICR-EPA (15%) and highest in AL-Con mice (87%), whereas AL-EPA, CCR-Con, CCR
      EPA, and ICR-Con groups had mammary tumor incidence rates of 63%, 47%, 40%, and
      59%, respectively. Survival was effected similarly by the interventions.
      Consumption of EPA dramatically reduced serum leptin (P < 0.02) and increased
      serum adiponectin in the AL-EPA mice compared with AL-Con mice (P < 0.001). Both
      CCR and ICR decreased serum leptin and insulin-like growth factor I (IGF-I)
      compared with AL mice but not compared with each other. These results illustrate
      that mammary tumor inhibition is significantly increased when ICR and EPA are
      combined as compared with either intervention alone. This response may be related
      to alterations in the balance of serum growth factors and adipokines.

PMID- 23550155
TI  - c-Myc phosphorylation by PKCzeta represses prostate tumorigenesis.
AB  - Studies showing reduced PKCzeta expression or enzymatic activity in different
      types of human cancers support the clinical relevance of PKCzeta as a tumor
      suppressor. However, the in vivo role of PKCzeta and its mechanisms of action in
      prostate cancer remain unclear. Here we demonstrate that the genetic inactivation
      of PKCzeta in mice results in invasive prostate carcinoma in vivo in the context
      of phosphatase and tensin homolog deficiency. Bioinformatic analysis of human
      prostate cancer gene-expression sets revealed increased c-Myc transcriptional
      activity in PKCzeta-inactive cells, which correlated with increased cell growth,
      invasion, and metastasis. Interestingly, PKCzeta knockdown or the overexpression
      of a kinase-inactive mutant resulted in enhanced cell proliferation and invasion
      in vitro through increased c-Myc mRNA and protein levels and decreased Ser-373
      phosphorylation of c-Myc. Analysis of prostate cancer samples demonstrated
      increased expression and decreased phosphorylation of c-Myc at Ser-373 in PKCzeta
      knockout tumors. In vivo xenograft studies revealed that c-Myc phosphorylation by
      PKCzeta is a critical event in the control of metastasis. Collectively, these
      results establish PKCzeta as an important tumor suppressor and regulator of c-Myc
      function in prostate cancer.

PMID- 23550156
TI  - Autoantigen can promote progression to a more aggressive TCL1 leukemia by
      selecting variants with enhanced B-cell receptor signaling.
AB  - (Auto)antigen engagement by the B-cell receptor (BCR) and possibly the sites
      where this occurs influence the outcome of chronic lymphocytic leukemia (CLL). To
      test if selection for autoreactivity leads to increased aggressiveness and if
      this selection plays out equally in primary and secondary tissues, we used T-cell
      leukemia (TCL)1 cells reactive with the autoantigen phosphatidylcholine (PtC).
      After repeated transfers of splenic lymphocytes from a single mouse with
      oligoclonal PtC-reactive cells, outgrowth of cells expressing a single IGHV-D-J
      rearrangement and superior PtC-binding and disease virulence occurred. In
      secondary tissues, increased PtC-binding correlated with enhanced BCR signaling
      and cell proliferation, whereas reduced signaling and division of cells from the
      same clone was documented in cells residing in the bone marrow, blood, and
      peritoneum, even though cells from the last site had highest surface membrane IgM
      density. Gene-expression analyses revealed reciprocal changes of genes involved
      in BCR-, CD40-, and PI3K-signaling between splenic and peritoneal cells. Our
      results suggest autoantigen-stimulated BCR signaling in secondary tissues
      promotes selection, expansion, and disease progression by activating pro
      oncogenic signaling pathways, and that--outside secondary lymphoid tissues-
      clonal evolution is retarded by diminished BCR-signaling. This transferrable,
      antigenic-specific murine B-cell clone (TCL1-192) provides a platform to study
      the types and sites of antigen-BCR interactions and genetic alterations that
      result and may have relevance to patients.

PMID- 23550157
TI  - RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA
      binding nuclear receptor coregulators.
AB  - The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding
      proteins, including protein kinase RNA activator (PACT), transactivation response
      RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature
      microRNAs (miRNAs) that target specific mRNA species for regulation. There is
      increasing evidence for important functional interactions between the miRNA and
      nuclear receptor (NR) signaling networks, with recent data showing that estrogen,
      acting through the estrogen receptor, can modulate initial aspects of nuclear
      miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP,
      and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that
      target steroid-responsive promoters and regulate NR activity and downstream gene
      expression. Furthermore, each of the RISC proteins, together with Argonaute 2,
      associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm,
      providing evidence for links between NR-mediated transcription and some of the
      factors involved in miRNA processing.

PMID- 23550158
TI  - Transgenic pig carrying green fluorescent proteasomes.
AB  - Among its many functions, the ubiquitin-proteasome system regulates substrate
      specific proteolysis during the cell cycle, apoptosis, and fertilization and in
      pathologies such as Alzheimer's disease, cancer, and liver cirrhosis. Proteasomes
      are present in human and boar spermatozoa, but little is known about the
      interactions of proteasomal subunits with other sperm proteins or structures. We
      have created a transgenic boar with green fluorescent protein (GFP) tagged 20S
      proteasomal core subunit alpha-type 1 (PSMA1-GFP), hypothesizing that the PSMA1
      GFP fusion protein will be incorporated into functional sperm proteasomes. Using
      direct epifluorescence imaging and indirect immunofluorescence detection, we have
      confirmed the presence of PSMA1-GFP in the sperm acrosome. Western blotting
      revealed a protein band corresponding to the predicted mass of PSMA1-GFP fusion
      protein (57 kDa) in transgenic spermatozoa. Transgenic boar fertility was
      confirmed by in vitro fertilization, resulting in transgenic blastocysts, and by
      mating, resulting in healthy transgenic offspring. Immunoprecipitation and
      proteomic analysis revealed that PSMA1-GFP copurifies with several acrosomal
      membrane-associated proteins (e.g., lactadherin/milk fat globule E8 and
      spermadhesin alanine-tryptophan-asparagine). The interaction of MFGE8 with PSMA1
      GFP was confirmed through cross-immunoprecipitation. The identified proteasome
      interacting proteins may regulate sperm proteasomal activity during fertilization
      or may be the substrates of proteasomal proteolysis during fertilization.
      Proteomic analysis also confirmed the interaction/coimmunoprecipitation of PSMA1
      GFP with 13/14 proteasomal core subunits. These results demonstrate that the
      PSMA1-GFP was incorporated in the assembled sperm proteasomes. This mammal
      carrying green fluorescent proteasomes will be useful for studies of
      fertilization and wherever the ubiquitin-proteasome system plays a role in
      cellular function or pathology.

PMID- 23550160
TI  - Bacterial protein-O-mannosylating enzyme is crucial for virulence of
      Mycobacterium tuberculosis.
AB  - A posttranslational protein O-mannosylation process resembling that found in
      fungi and animals has been reported in the major human pathogen Mycobacterium
      tuberculosis (Mtb) and related actinobacteria. However, the role and incidence of
      this process, which is essential in eukaryotes, have never been explored in Mtb.
      We thus analyzed the impact of interrupting O-mannosylation in the nonpathogenic
      saprophyte Mycobacterium smegmatis and in the human pathogen Mtb by inactivating
      the respective putative protein mannosyl transferase genes Msmeg_5447 and
      Rv1002c. Loss of protein O-mannosylation in both mutant strains was unambiguously
      demonstrated by efficient mass spectrometry-based glycoproteomics analysis.
      Unexpectedly, although the M. smegmatis phenotype was unaffected by the lack of
      manno-proteins, the Mtb mutant had severely impacted growth in vitro and in
      cellulo associated with a strong attenuation of its pathogenicity in
      immunocompromised mice. These data are unique in providing evidence of the
      biological significance of protein O-mannosylation in mycobacteria and
      demonstrate the crucial contribution of this protein posttranslational
      modification to Mtb virulence in the host.

PMID- 23550161
TI  - Transcription factors interfering with dedifferentiation induce cell type
      specific transcriptional profiles.
AB  - Transcription factors (TFs) are able to regulate differentiation-related
      processes, including dedifferentiation and direct conversion, through the
      regulation of cell type-specific transcriptional profiles. However, the
      functional interactions between the TFs regulating different transcriptional
      profiles are not well understood. Here, we show that the TFs capable of inducing
      cell type-specific transcriptional profiles prevent the dedifferentiation induced
      by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage
      cell line, we identified a subset of TFs that, when overexpressed, strongly
      interfered with the dedifferentiation triggered by the procedure to generate
      induced pluripotent stem cells. This interference occurred through a maintenance
      mechanism of the cell type-specific transcriptional profile. Strikingly, the
      maintenance activity of the interfering TF set was strong enough to induce the
      cell line-specific transcriptional profile when overexpressed in a heterologous
      cell type. In addition, the TFs that interfered with dedifferentiation in hepatic
      lineage cells involved TFs with known induction activity for hepatic-lineage
      cells. Our results suggest that dedifferentiation suppresses a cell type-specific
      transcriptional profile, which is primarily maintained by a small subset of TFs
      capable of inducing direct conversion. We anticipate that this functional
      correlation might be applicable in various cell types and might facilitate the
      identification of TFs with induction activity in efforts to understand
      differentiation.

PMID- 23550163
TI  - PDE8A runs interference to limit PKA inhibition of Raf-1.

PMID- 23550162
TI  - Procollagen C-proteinase enhancer grasps the stalk of the C-propeptide trimer to
      boost collagen precursor maturation.
AB  - Tight regulation of collagen fibril deposition in the extracellular matrix is
      essential for normal tissue homeostasis and repair, defects in which are
      associated with several degenerative or fibrotic disorders. A key regulatory step
      in collagen fibril assembly is the C-terminal proteolytic processing of soluble
      procollagen precursors. This step, carried out mainly by bone morphogenetic
      protein-1/tolloid-like proteinases, is itself subject to regulation by
      procollagen C-proteinase enhancer proteins (PCPEs) which can dramatically
      increase bone morphogenetic protein-1/tolloid-like proteinase activity, in a
      substrate-specific manner. Although it is known that this enhancing activity
      requires binding of PCPE to the procollagen C-propeptide trimer, identification
      of the precise binding site has so far remained elusive. Here, use of small-angle
      X-ray scattering provides structural data on this protein complex indicating that
      PCPE binds to the stalk region of the procollagen C-propeptide trimer, where the
      three polypeptide chains associate together, at the junction with the base
      region. This is supported by site-directed mutagenesis, which identifies two
      highly conserved, surface-exposed lysine residues in this region of the trimer
      that are essential for binding, thus revealing structural parallels with the
      interactions of Complement C1r/C1s, Uegf, BMP-1 (CUB) domain-containing proteins
      in diverse biological systems such as complement activation, receptor signaling,
      and transport. Together with detailed kinetics and interaction analysis, these
      results provide insights into the mechanism of action of PCPEs and suggest clear
      strategies for the development of novel antifibrotic therapies.

PMID- 23550164
TI  - Functional flexibility of infant vocalization and the emergence of language.
AB  - We report on the emergence of functional flexibility in vocalizations of human
      infants. This vastly underappreciated capability becomes apparent when
      prelinguistic vocalizations express a full range of emotional content--positive,
      neutral, and negative. The data show that at least three types of infant
      vocalizations (squeals, vowel-like sounds, and growls) occur with this full range
      of expression by 3-4 mo of age. In contrast, infant cry and laughter, which are
      species-specific signals apparently homologous to vocal calls in other primates,
      show functional stability, with cry overwhelmingly expressing negative and
      laughter positive emotional states. Functional flexibility is a sine qua non in
      spoken language, because all words or sentences can be produced as expressions of
      varying emotional states and because learning conventional "meanings" requires
      the ability to produce sounds that are free of any predetermined function.
      Functional flexibility is a defining characteristic of language, and empirically
      it appears before syntax, word learning, and even earlier-developing features
      presumed to be critical to language (e.g., joint attention, syllable imitation,
      and canonical babbling). The appearance of functional flexibility early in the
      first year of human life is a critical step in the development of vocal language
      and may have been a critical step in the evolution of human language, preceding
      protosyntax and even primitive single words. Such flexible affect expression of
      vocalizations has not yet been reported for any nonhuman primate but if found to
      occur would suggest deep roots for functional flexibility of vocalization in our
      primate heritage.

PMID- 23550166
TI  - A study into efficacy of omalizumab therapy in patients with severe persistent
      allergic asthma at a tertiary referral centre for asthma in Ireland.
AB  - BACKGROUND: Asthma is a chronic airway disease characterized by airway
      inflammation, bronchial hyperresponsiveness and airflow obstruction. Patients
      with persistent symptoms despite maximum standard treatment as per Global
      Initiative of Asthma guidelines are considered to have severe persistent asthma.
      Omalizumab is a recombinant humanized monoclonal antibody licenced for use as an
      add-on therapy in these patients. AIM: To assess the clinical benefit amongst
      responders to omalizumab therapy at a tertiary referral centre. METHODS: This was
      a retrospective audit assessing the effect of omalizumab therapy on asthma
      control, frequency of exacerbation and hospitalization rates over 6 months before
      and after therapy. RESULTS: The study included 30 responders (14 females). There
      was a reduction in exacerbation and hospitalization rates following initiation of
      omalizumab, 73 and 91%, respectively (P-value < 0.0001). The number of
      exacerbations decreased from 3.48 +/- 2.20 to 0.93 +/- 0.83 and the mean number
      of admissions decreased from 1.07 +/- 1.1 to 0.1 +/- 0.40 over the study duration
      (P < 0.001). There was 73% reduction in the weekly need for rescue salbutamol
      therapy with mean of 30.33 +/- 6.49 puffs to 8.23 +/- 1.51 puffs after omalizumab
      therapy (P < 0.0001). Seventy-nine per cent of patients were able to reduce their
      maintenance oral corticosteroid therapy. CONCLUSION: Overall, responders to
      omalizumab therapy are less likely to experience an asthma exacerbation and
      hospitalization. They were also more likely to reduce maintenance corticosteroid
      therapy and the need for rescue reliever therapy. These data suggest that
      omalizumab has proven effective in improving health outcomes for a cohort of
      carefully selected patients with severe allergic asthma in Ireland.

PMID- 23550165
TI  - Tool-use practice induces changes in intrinsic functional connectivity of
      parietal areas.
AB  - Intrinsic functional connectivity from resting state functional magnetic
      resonance imaging (rsfMRI) has increasingly received attention as a possible
      predictor of cognitive function and performance. In this study, we investigated
      the influence of practicing skillful tool manipulation on intrinsic functional
      connectivity in the resting brain. Acquisition of tool-use skill has two aspects
      such as formation of motor representation for skillful manipulation and
      acquisition of the tool concept. To dissociate these two processes, we chose
      chopsticks-handling with the non-dominant hand. Because participants were already
      adept at chopsticks-handling with their dominant hand, practice with the non
      dominant hand involved only acquiring the skill for tool manipulation with
      existing knowledge. Eight young participants practiced chopsticks-handling with
      their non-dominant hand for 8 weeks. They underwent functional magnetic resonance
      imaging (fMRI) sessions before and after the practice. As a result, functional
      connectivity among tool-use-related regions of the brain decreased after
      practice. We found decreased functional connectivity centered on parietal areas,
      mainly the supramarginal gyrus (SMG) and superior parietal lobule (SPL) and
      additionally between the primary sensorimotor area and cerebellum. These results
      suggest that the parietal lobe and cerebellum purely mediate motor learning for
      skillful tool-use. This decreased functional connectivity may represent increased
      efficiency of functional network.

PMID- 23550167
TI  - The predictive value of hospital admission serum alanine transaminase activity in
      patients treated for paracetamol overdose.
AB  - BACKGROUND: Paracetamol is a major cause of poisoning. Treatment decisions are
      predominately based on the dose ingested and a timed blood paracetamol
      concentration because most patients present to hospital soon after overdose,
      before hepatotoxicity can be confirmed/excluded using serum alanine transaminase
      (ALT). Nonetheless, ALT is measured at hospital presentation; we investigated its
      value in predicting hepatotoxicity. METHODS: From March 2011 to May 2012,
      patients admitted to the Royal Infirmary of Edinburgh for paracetamol overdose
      treatment were identified. We determined the value of admission ALT (below or
      above our upper limit of normal-50 IU/l) at predicting three endpoints: 1
      doubling of ALT; 2-peak ALT >1000 IU/l; 3-peak international normalized ratio
      (INR) >2. RESULTS: From 500 patients, 410 met the entry criteria; 264 presented
      within 8 h of overdose, 54 between 8 and 24 h, 53 after 24 h and 39 were
      staggered ingestions. Admission ALT was increased in 71. For endpoint 1 (ALT
      doubling), the positive predictive value (PPV) of admission ALT was 19% [95%
      confidence interval (CI) 12-30] with a negative predictive value (NPV) of 98%
      (95% CI 96-99); endpoint 2 (ALT >1000 IU/l: PPV 23% (95% CI 14-34) and NPV 100%
      (95% CI 99-100) and for endpoint 3 (INR >2): PPV 14% (95% CI 7-25) and NPV of
      100% (95% CI 99-100). The NPV remained high when only late presenters were
      included. CONCLUSION: Admission ALT within the normal range has a high NPV and
      could be used, alone or in combination with newer biomarkers, to identify lower
      risk patients at hospital presentation.

PMID- 23550168
TI  - The relationship between alexithymia, shame, trauma, and body image disorders:
      investigation over a large clinical sample.
AB  - BACKGROUND: The connections between eating disorders (EDs) and alexithymia have
      not been fully clarified. This study aims to define alexithymia's connections
      with shame, trauma, dissociation, and body image disorders. METHODS: We
      administered the Dissociative Experience Scale-II, Trauma Symptom Inventory,
      Experience of Shame Scale, Toronto Alexithymia Scale-20, and Body Uneasiness Test
      questionnaires to 143 ED subjects. Extensive statistical analyses were performed.
      RESULTS: The subjects showed higher scores on alexithymia, shame, dissociation,
      and traumatic feelings scales than the nonclinical population. These aspects are
      linked with each other in a statistically significant way. Partial correlations
      highlighted that feelings of shame are correlated to body dissatisfaction,
      irrespective of trauma or depressed mood. Multiple regression analysis
      demonstrates that shame (anorexic patients) and perceived traumatic conditions
      (bulimic and ED not otherwise specified) are associated with adverse image
      disorders. CONCLUSION: Shame seems to hold a central role in the perception of an
      adverse self-image. Alexithymia may be interpreted as being a consequence of
      previous unelaborated traumatic experiences and feelings of shame, and it could
      therefore be conceptualized as a maladaptive-reactive construct.

PMID- 23550169
TI  - Ovarian and placental morphology and endocrine functions in the pregnant giraffe
      (Giraffa camelopardalis).
AB  - Gross, histological and immunocytochemical examinations carried out on maternal
      and fetal reproductive tissues from two pregnant giraffes at an estimated 8 and
      13.5 months of gestation (term=15 months) revealed a typically ruminant
      macrocotyledonary placenta with binucleate trophoblast cells scattered sparsely
      in the placentome where they stained intensely with a prolactin antiserum.
      Binucleate cells were present in greater numbers in the intercotyledonary
      allantochorion where they did not stain for prolactin whereas the uninucleate
      trophoblast still did. A single large corpus luteum of pregnancy and several
      small luteinised follicles were present in the maternal ovaries while the fetal
      ovaries at 13.5 months gestation showed an assortment of enlarging antral
      follicles and partially and completely lutenised follicles, the granulosa and
      luteal cells of which stained positively for 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD), 17,20 lyase, prolactin, progesterone receptor and androgen receptor,
      but negatively for aromatase. The uninucleate trophoblast of the placentome and
      intercotyledonary allantochorion, the epithelium of the maternal endometrial
      glands, the seminiferous epithelium in the fetal testis at 8 months of gestation
      and the zonae fasciculata and reticularis of the fetal adrenal at 13.5 months
      also stained positively for 3beta-HSD and negatively for aromatase.
      Endocrinologically, it appears that the giraffe placenta is more similar to that
      of the sheep than the cow with a placental lactogen as the likely driver of the
      considerable degree of luteinisation seen in both the maternal and the fetal
      ovaries.

PMID- 23550170
TI  - Gorham syndrome with postoperative respiratory failure and requiring prolonged
      mechanical ventilation.
AB  - Gorham syndrome is a rare disease that presents as progressive osteolysis, and
      may affect any part of the skeleton. The pathologic process involves the
      replacement of normal bone by aggressively expanding but non-neoplastic vascular
      tissue, resulting in massive osteolysis of the adjacent bone. If the spine and
      ribs are affected, the subsequent kyphosis and chest wall deformity may cause
      severe restrictive ventilatory impairment. We report a 34-year-old male with
      Gorham syndrome presenting as progressive kyphosis, severe back pain, unstable
      gait, and exertional dyspnea. Pulmonary function testing revealed severe
      restrictive ventilatory impairment. He underwent spinal surgery but could not be
      extubated after surgery. Postoperative left lower lung pneumonia and respiratory
      failure required prolonged mechanical ventilation. After a weaning program of
      pressure support ventilation and T-piece spontaneous breathing trials, he was
      successfully weaned from mechanical ventilation. 

PMID- 23550171
TI  - A comparative study of 3 portable oxygen concentrators during a 6-minute walk
      test in patients with chronic lung disease.
AB  - BACKGROUND: The purpose of this study was to compare the ability of 3 portable
      oxygen concentrators (POCs) to maintain S(pO2) >= 90% during exercise in patients
      with chronic lung disease. METHODS: Twenty-one subjects with chronic lung disease
      (18 with COPD, 3 with pulmonary fibrosis) and documented room air exertional
      S(pO2) <= 85% performed four 6-min walk tests: a control walk using the subject's
      current oxygen system and prescribed exertional flow rate, and 1 walk with each
      of the 3 POCs (Eclipse 3, EverGo, and iGo) at their maximum pulse-dose setting.
      RESULTS: S(pO2) was significantly higher pre-walk and post-walk with the Eclipse
      3, compared to the other POCs (all P < .01). The subjects also walked farther and
      maintained a mean S(pO2) >= 90% with the Eclipse 3 (both P < .01), which delivers
      the largest oxygen bolus. The subjects indicated that they preferred the EverGo's
      physical characteristics, but that the Eclipse 3 responded best to their
      breathing. The iGo was rated less favorably than Eclipse 3 or EverGo.
      CONCLUSIONS: The Eclipse 3 was best at meeting the subjects' clinical needs. POC
      users should be appropriately tested during all activities of daily living, to
      ensure adequate oxygenation. The healthcare provider should provide information
      and help to direct the subject toward the most clinically appropriate oxygen
      system, while being mindful of the patient's preferences and lifestyle.
      (Clinicaltrials.gov NCT01653730).

PMID- 23550172
TI  - Profound bradycardia with decreased PEEP.
AB  - An athletic 21-year-old male was admitted to the surgical ICU after sustaining 2
      stab wounds to his torso. He had an episode of left lung collapse early in his
      course, managed with suctioning and increased PEEP, to 15 cm H2O. He was
      bradycardic (heart rates 50-60 beats/min) throughout his ICU stay, but when the
      PEEP was lowered to 5 cm H2O in preparation for extubation, he developed sinus
      pauses and his heart rate dropped to 20 beats/min. After a thorough evaluation,
      the drop in his heart rate was determined to be due to increased vagal tone from
      increased cardiac output with the decreased PEEP. After premedication with
      glycopyrrolate, he was successfully extubated the following day, while his heart
      rate remained at his baseline of 50 beats/min. We review the physiologic
      mechanisms of bradycardia due to the removal of mechanical ventilation. 

PMID- 23550173
TI  - Transposable element proliferation as a possible side effect of endosymbiont
      manipulations.
AB  - The mode of reproduction has been predicted to affect the proliferation of
      transposable elements (TEs). A population that switches from sexual to asexual
      reproduction could either accumulate TEs because purifying selection becomes less
      efficient, or a decrease in TE load because the opportunity for horizontal
      transmission is reduced. A third possibility is that the mechanism that induces
      asexual reproduction affects TE dynamics as a side effect. We propose two such
      mechanisms that might explain recently described patterns of TE abundance in
      sexual and asexual lineages of the parasitoid wasp Leptopilina clavipes. Asexual
      reproduction in this species is induced by endosymbiotic Wolbachia bacteria. In
      order to achieve parthenogenesis in its host, Wolbachia might remove methylation
      or interfere with Argonaute proteins. Both methylation and Argonaute proteins are
      known to control TE activity in other species. By interfering with either,
      Wolbachia might therefore secondarily hamper the control of specific TEs.

PMID- 23550174
TI  - Efficacy of alfuzosin after shock wave lithotripsy for the treatment of ureteral
      calculi.
AB  - PURPOSE: We evaluated the efficacy of alfuzosin for the treatment of ureteral
      calculi less than 10 mm in diameter after extracorporeal shock wave lithotripsy
      (ESWL). MATERIALS AND METHODS: A randomized, single-blind clinical trial was
      performed prospectively by one physician between June 2010 and August 2011. A
      total of 84 patients with ureteral calculi 5 to 10 mm in diameter were divided
      into two groups. Alfuzosin 10 mg (once daily) and loxoprofen sodium 68.1 mg (as
      needed) were prescribed to group 1 (n=41), and loxoprofen sodium 68.1 mg (as
      needed) only was prescribed to group 2 (n=44). The drug administration began
      immediately after ESWL and continued until stone expulsion was confirmed up to a
      maximum of 42 days after the procedure. RESULTS: Thirty-nine of 41 (95.1%)
      patients in group 1 and 40 of 43 (93.0%) patients in group 2 ultimately passed
      stones (p=0.96). The number of ESWL sessions was 1.34+/-0.65 and 1.41+/-0.85 in
      groups 1 and 2, respectively (p=0.33). The patients who required analgesics after
      ESWL were 8 (19.5%) in group 1 and 13 (30.2%) in group 2 (p=0.31). Visual
      analogue scale pain severity scores were 5.33+/-1.22 and 6.43+/-1.36 in groups 1
      and 2, respectively (p=0.056). The time to stone expulsion in groups 1 and 2 was
      9.5+/-4.8 days and 14.7+/-9.8 days, respectively (p=0.005). No significant
      adverse effects occurred. CONCLUSIONS: The use of alfuzosin in combination with
      ESWL seems to facilitate stone passage and to reduce the time of stone expulsion
      but does not affect the stone-free rate.

PMID- 23550175
TI  - High Prevalence of Sleep Problems in School- and Preschool-aged Children in
      Tehran: a Population Based Study.
AB  - OBJECTIVE: Sleep problems are experienced by 25-30 percent of children and
      adolescents, regardless of age. The purpose of this study was to investigate if
      there is any relationship between gender or school entrance and sleep complaints.
      METHODS: From June 2008 to May 2009 children aged 2 to 12 years were selected by
      clustered randomization of families. The Persian version of the BEARS
      questionnaire (Bedtime problems, Excessive sleepiness, Awakenings during the
      night, Regularity of sleep, Snoring) with five domains was filled out by general
      pediatricians. Prevalence of sleep complaints in each B-E-A-R-S category was
      calculated and compared for pre-school and school-age groups. FINDINGS: BEARS
      questionnaire was completed for a total of 746 children (2-12 years old); 325 in
      pre-school-age group (2-6 years old) (142 females [43.7%] and 183 males [56.3%])
      and 421 in primary school-age group (7-12 years old) with the average age of 3.93
      (+/-0.16) years and 9.63 (+/-0.16) years respectively. The most common screening
      problem in both groups was excessive daytime sleepiness (64.9% and 62.9%
      respectively). Bedtime problems and also regularity and duration of sleep were
      significantly more prevalent in pre-school-age group (P<0.0002; odds ratio [OR]
      =1.98; 95% confidence interval [95%CI]: 1.98-4.20; and OR=2.00; 95%CI: 1.41- 2.84
      respectively). The difference between mean sleep duration between pre-school age
      and school-age groups was statistically significant (P<0.0001). CONCLUSION: The
      current survey shows that different types of sleep problems are relatively high
      especially in the form of excessive daytime sleeping domain in preschool- and
      school-aged children. Bedtime problems and regularity problems were significantly
      more prevalent in pre-school-age group. School entrance seems to play a positive
      role for bedtime problems, and sleep-disordered breathing.

PMID- 23550177
TI  - Distribution of radionuclides and radiation hazard assessment in soils of
      Southern Namibia, Southern Africa.
AB  - The activity concentrations of (238)U, (232)Th and (40)K in soil samples taken
      from four major towns across southern Namibia have been determined by gamma
      spectroscopy and used to calculate the mean dose rate, radium equivalent activity
      (Raeq) and external hazard index (Hex) for each town. The average concentrations
      of radionuclides in the towns vary from 10.7+/-3.1 to 35.6+/-8.4 Bq kg(-1) for
      (238)U, 12.3+/-4.9 to 77.8+/-20.9 Bq kg(-1) for (232)Th and 248.0+/-35.6 to
      734.6+/-61.4 Bq kg(-1) for (40)K. These values are within the range of
      concentrations reported in some countries but most of the values for (232)Th and
      (40)K are above the worldwide averages. However, the mean effective dose rate of
      0.08+/-0.03 mSv y(-1) and the mean values of Raeq and Hex for the region are
      below their respective permissible limits, thus indicating that radiation hazard
      is negligible in the region. 

PMID- 23550176
TI  - Controllability modulates the anticipatory response in the human ventromedial
      prefrontal cortex.
AB  - Research has consistently shown that control is critical to psychological
      functioning, with perceived lack of control considered to play a crucial role in
      the manifestation of symptoms in psychiatric disorders. In a model of behavioral
      control based on non-human animal work, Maier et al. (2006) posited that the
      presence of control activates areas of the ventromedial prefrontal cortex
      (vmPFC), which in turn inhibit the normative stress response in the dorsal raphe
      nucleus and amygdala. To test Maier's model in humans, we investigated the
      effects of control over potent aversive stimuli by presenting video clips of
      snakes to 21 snake phobics who were otherwise healthy with no comorbid
      psychopathologies. Based on prior research documenting that disrupted neural
      processing during the anticipation of adverse events can be influenced by
      different forms of cognitive processing such as perceptions of control, analyses
      focused on the anticipatory activity preceding the videos. We found that phobics
      exhibited greater vmPFC activity during the anticipation of snake videos when
      they had control over whether the videos were presented as compared to when they
      had no control over the presentation of the videos. In addition, observed
      functional connectivity between the vmPFC and the amygdala is consistent with
      previous work documenting vmPFC inhibition of the amygdala. Our results provide
      evidence to support the extension of Maier's model of behavioral control to
      include anticipatory function in humans.

PMID- 23550178
TI  - Promising New Approaches to Assess Cognitive Functioning in People with Multiple
      Sclerosis.
AB  - Cognitive impairment has a major impact on the lives of people with Multiple
      Sclerosis (MS). Yet, it is often under-diagnosed, and more effective assessment
      methods are needed. In particular, brief measures that focus on cognitive
      functioning in daily life situations, are sensitive to modest change over time,
      and do not require a highly skilled assessor merit exploration. The purpose of
      this exploratory study was to investigate the performance of individuals with MS
      on three relatively new measures: the PROMIS Cognitive Concerns and Abilities
      Scales and the Everyday Problems Test (EPT), and to compare scores on these
      measures with scores on neurocognitive performance measures typically used to
      assess cognitive functioning in people with MS. Twenty-nine individuals with MS
      who reported cognitive concerns participated in the study. Most were non-Hispanic
      White women, with relapsing-remitting MS, diagnosed approximately 18 years ago.
      All three measures yielded reliability coefficients of .80 or above and also
      demonstrated sensitivity to change following an educational intervention. Scores
      on the revised EPT were moderately correlated with scores on five standard
      neuropsychological measures. Compared with the PROMIS Cognitive Concerns scale,
      scores on the self-reported PROMIS Cognitive Abilities scale tended to correlate
      more highly with the neurocognitive performance measures, although the
      correlations were generally small. While results of this exploratory study are
      promising, future research should be conducted with larger and more diverse
      samples of people with MS to determine the broader utility of these measures.

PMID- 23550179
TI  - Influenza-virus membrane fusion by cooperative fold-back of stochastically
      induced hemagglutinin intermediates.
AB  - Influenza virus penetrates cells by fusion of viral and endosomal membranes
      catalyzed by the viral hemagglutinin (HA). Structures of the initial and final
      states of the HA trimer define the fusion endpoints, but do not specify
      intermediates. We have characterized these transitions by analyzing low-pH
      induced fusion kinetics of individual virions and validated the analysis by
      computer simulation. We detect initial engagement with the target membrane of
      fusion peptides from independently triggered HAs within the larger virus-target
      contact patch; fusion then requires engagement of three or four neighboring HA
      trimers. Effects of mutations in HA indicate that withdrawal of the fusion
      peptide from a pocket in the pre-fusion trimer is rate-limiting for both events,
      but the requirement for cooperative action of several HAs to bring the fusing
      membranes together leads to a long-lived intermediate state for single, extended
      HA trimers. This intermediate is thus a fundamental aspect of the fusion
      mechanism. DOI:http://dx.doi.org/10.7554/eLife.00333.001.

PMID- 23550180
TI  - Linagliptin: A thorough Characterization beyond Its Clinical Efficacy.
AB  - Linagliptin, one of the five dipeptidyl peptidase-4 inhibitors available, has
      recently entered the market both in the US and in most European countries for
      treatment of type 2 diabetes mellitus. It presents a xanthine-based structure,
      and is characterized by unique pharmacokinetics, with non-linear profile, long
      terminal half-life allowing prolonged exposure to the drug. It is eliminated
      predominately through the intestinal tract and only minimally into urine, so that
      it can be administered, without any dose adjustment, in conditions of renal
      impairment. Linagliptin is effective in modifying all parameters of hyperglycemia
      either in monotherapy, or as add-on therapy, together with metformin or a
      sulfonylurea. It also exhibits a good tolerability profile with few side effects,
      absence (when used in monotherapy), or low risk (when in combination with a
      sulfonylurea) of hypoglycemia. More importantly it has a weight neutral effect. A
      comprehensive report of the literature on linagliptin is provided, paying
      attention in particular to preclinical studies, interactions with other drugs,
      safety and tolerability, and results obtained in animal models that highlight
      properties of linagliptin suggestive of potential additional uses. Particularly
      promising appear the data demonstrating a positive effect of linagliptin on
      metabolic dysfunction and renal and/or cardiovascular damage together with more
      recently reported effects of linagliptin on tissue repair and neuroprotection.

PMID- 23550181
TI  - MR cisternography/myelography of post-traumatic spinal CSF fistulae and meningeal
      lesions in small animals.
AB  - BACKGROUND: The diagnosis of post-traumatic spinal cerebrospinal fluid (CSF)
      fistulae due to dural tears or lesions remains a challenge. Thus far, CT
      myelography is the standard test used to diagnose these complications. PURPOSE:
      To evaluate the diagnostic ability of gadolinium-enhanced MR
      cisternography/myelography (intrathecal gadopentate dimeglumine or Gd-DTPA) in
      small animals that had experienced accidental spinal trauma. MATERIAL AND
      METHODS: Four dogs and one cat suffered traumatic accidents resulting in
      neurological deficits underwent spinal MRI with intrathecal Gd-DTPA after routine
      plain films and MR images. RESULTS: T2-weighted SE images showed high water
      content in the epidural space or in the surroundings of the vertebrae in four
      animals. MR myelography revealed CSF leakage in all of them. In two animals CSF
      leaks were observed exuding from the spinal canal and tracking towards adjacent
      loose fat and interfascial planes. In two other animals Gd-DTPA extravasation was
      diffusely collected in paraspinal tissues around the vertebral arch. In the fifth
      animal a focal pseudomeningocele was observed adjacent to the traumatized region.
      CONCLUSION: Intrathecal administration of Gd-DTPA is an effective method to
      reveal and confirm post-traumatic spinal CSF fistulae or other dural lesions in
      animals with potential application in humans.

PMID- 23550182
TI  - Adenosine-stress low-dose single-scan CT myocardial perfusion imaging using a 128
      slice dual-source CT: a comparison with fractional flow reserve.
AB  - BACKGROUND: Coronary CT angiography (CCTA) allows accurate evaluation of coronary
      artery stenosis but has limitations in information on hemodynamic significance of
      stenotic lesions. PURPOSE: To determine the feasibility of adenosine-stress low
      dose single-scan CT myocardial perfusion imaging (MPI) using a 128-slice dual
      source CT scanner for the diagnosis of hemodynamically significant coronary
      artery stenosis as defined by fractional flow reserve (FFR). MATERIAL AND
      METHODS: This study was proved by the Institutional Review Board and informed
      consent was obtained from the patients before enrollment in the study. Ninety
      seven patients with chest pain and low-to-intermediate pretest probability of
      coronary artery disease were prospectively enrolled. Adenosine-stress CCTA using
      ECG-correlated maximum tube current modulation (Mindose((r))) with 128-slice dual
      source CT was performed in all 97 patients. In 37 patients (38.1%; 28 men, nine
      women; mean age, 61.7 +/- 20.5 years; mean heart rate, 74.6 +/- 2.8 bpm) with
      significant stenosis at CCTA (lumen diameter reduction >50%), FFR was performed
      after CCTA, as a reference standard for the evaluation of myocardial perfusion.
      FFR value <=0.75 was considered as positive. CTMPI and CCTA were read by two
      experienced radiologists with consensus, respectively. RESULTS: The effective
      radiation dose of adenosine-stress single-scan CTMPI was 4.63 +/- 2.57 mSv.
      Compared with FFR, sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) for identifying significant coronary stenoses
      were 93.1%, 82.7%, 75.0%, and 95.6%, respectively, on CCTA and 93.1%, 90.3%,
      84.4%, and 95.9%, respectively, on CTMPI. On combined CCTA and CTMPI,
      sensitivity, specificity, PPV, and NPV were 93.1%, 94.2%, 90.0%, and 96.0%,
      respectively. CONCLUSION: Adenosine-stress low-dose single scan CTMPI using a 128
      slice dual-source CT can provide complementary information on the hemodynamical
      significance of coronary artery stenosis as well as anatomical information of
      coronary arteries.

PMID- 23550183
TI  - Sigmoid sinus diverticulum and pulsatile tinnitus: analysis of CT scans from 15
      cases.
AB  - BACKGROUND: Although the imaging features of sigmoid sinus diverticulum induced
      pulsatile tinnitus (PT) have been presented in some extent, detailed imaging
      findings still have not been systematically evaluated and precise diagnostic
      radiographic criteria has not been established. PURPOSE: To examine the computed
      tomography (CT) characteristics of sigmoid sinus diverticulum accompanied with
      PT. MATERIAL AND METHODS: Fifteen PT patients with sigmoid sinus diverticula
      proven by surgery were recruited after consenting. CT images of 15 patients were
      obtained and analyzed, including features of diverticula, brain venous systems,
      integrity of the sigmoid plate, and the degree of temporal bone pneumatization.
      RESULTS: Sigmoid sinus diverticulum was located on the same side of PT in 15
      patients. Diverticula originated at the superior curve of the sigmoid sinus in 11
      patients and the descending segment of the sigmoid sinus in four patients.
      Sigmoid sinus diverticula focally eroded into the adjacent mastoid air cells in
      12 patients and mastoid cortex in three patients. Among eight patients with
      unilateral dominant brain venous systems, the diverticula were seen on the
      dominant side in seven patients and non-dominant side in one patient. In
      contrast, the other seven patients showed co-dominant brain venous systems, with
      three presenting diverticula on the right side and four on the left. More
      notably, dehiscent sigmoid plate on the PT side was demonstrated in all patients.
      In addition, temporal bone hyper-pneumatization was found in nine patients, good
      and moderate pneumatization in three patients, respectively. CONCLUSION:
      Dehiscent sigmoid plate and extensive temporal bone pneumatization are two
      important imaging characteristics of the PT induced by sigmoid sinus
      diverticulum.

PMID- 23550184
TI  - The preliminary exploration of 64-slice volume computed tomography in the
      accurate measurement of pleural effusion.
AB  - BACKGROUND: Using computed tomography (CT) to rapidly and accurately quantify
      pleural effusion volume benefits medical and scientific research. However, the
      precise volume of pleural effusions still involves many challenges and currently
      does not have a recognized accurate measuring. PURPOSE: To explore the
      feasibility of using 64-slice CT volume-rendering technology to accurately
      measure pleural fluid volume and to then analyze the correlation between the
      volume of the free pleural effusion and the different diameters of the pleural
      effusion. MATERIAL AND METHODS: The 64-slice CT volume-rendering technique was
      used to measure and analyze three parts. First, the fluid volume of a self-made
      thoracic model was measured and compared with the actual injected volume. Second,
      the pleural effusion volume was measured before and after pleural fluid drainage
      in 25 patients, and the volume reduction was compared with the actual volume of
      the liquid extract. Finally, the free pleural effusion volume was measured in 26
      patients to analyze the correlation between it and the diameter of the effusion,
      which was then used to calculate the regression equation. RESULTS: After using
      the 64-slice CT volume-rendering technique to measure the fluid volume of the
      self-made thoracic model, the results were compared with the actual injection
      volume. No significant differences were found, P = 0.836. For the 25 patients
      with drained pleural effusions, the comparison of the reduction volume with the
      actual volume of the liquid extract revealed no significant differences, P =
      0.989. The following linear regression equation was used to compare the pleural
      effusion volume (V) (measured by the CT volume-rendering technique) with the
      pleural effusion greatest depth (d): V = 158.16 * d - 116.01 (r = 0.91, P =
      0.000). The following linear regression was used to compare the volume with the
      product of the pleural effusion diameters (l * h * d): V = 0.56 * (l * h * d) +
      39.44 (r = 0.92, P = 0.000). CONCLUSION: The 64-slice CT volume-rendering
      technique can accurately measure the volume in pleural effusion patients, and a
      linear regression equation can be used to estimate the volume of the free pleural
      effusion.

PMID- 23550185
TI  - Proposal to utilize simplified Swensen protocol in diagnosis of isolated
      pulmonary nodule.
AB  - BACKGROUND: The problem of diagnosing whether a solitary pulmonary nodule is
      benign or malignant is even greater in developing countries due to a higher
      prevalence of infectious diseases. These infections generate a large number of
      patients who are generally asymptomatic and with a pulmonary nodule that cannot
      be accurately defined as having benign or malignant etiology. PURPOSE: To verify
      the percentages of benign versus malignant non-calcified nodules, the length of
      time after contrast agent injection is spiral computed tomography (CT) most
      sensitive and specific, and whether three postcontrast phases are necessary.
      MATERIAL AND METHODS: We studied 23 patients with solitary pulmonary nodules
      identified on chest radiographs or CT. Spiral scans were obtained with Swensen
      protocol, but at 3, 4, and 5 min after contrast injection onset. Nodules were
      classified as benign or malignant by histopathological examination or by an
      absence or presence of growth after 2 years of follow-up CT. RESULTS: Of the 23
      patients studied, 18 (78.2%) showed a final diagnosis of benign and five (21.7%)
      malignant nodules. Despite the small sample size, we obtained results similar to
      those of Swensen et al., with 80.0% sensitivity, 55.5% specificity, and 60.8%
      accuracy. Four minutes gave the greatest mean enhancement in both malignant and
      benign lesions. CONCLUSION: Small non-calcified benign nodules were much more
      frequent than malignant nodules. The best time for dynamic contrast-enhanced CT
      density analysis was 4 min postcontrast. As well as saving time and money, this
      simplified Swensen protocol with only precontrast and 4 min postcontrast phases
      also reduces patient exposure to ionizing radiation.

PMID- 23550186
TI  - Potentials of high resolution magnetic resonance imaging versus computed
      tomography for preoperative local staging of colon cancer.
AB  - BACKGROUND: Preoperative identification of locally advanced colon cancer is of
      importance in order to properly plan treatment. PURPOSE: To study high resolution
      T2-weighted magnetic resonance imaging (MRI) versus computed tomography (CT) for
      preoperative staging of colon cancer with surgery and histopathology as reference
      standard. MATERIAL AND METHODS: Twenty-eight patients with a total of 29 tumors
      were included. Patients were examined on a 1.5 T MR unit using a phased array
      body coil. T2 turbo spin-echo high resolution sequences were obtained in a
      coronal, transverse, and perpendicular plane to the long axis of the colon at the
      site of the tumor. Contrast-enhanced CT was performed using a protocol for
      metastasis staging. The examinations were independently evaluated by two
      gastrointestinal radiologists using criteria adapted to imaging for prediction of
      T-stage, N-stage, and extramural venous invasion. Based on the T-stage, tumors
      were divided in to locally advanced (T3cd-T4) and not locally advanced (T1-T3ab).
      Surgical and histopathological findings served as reference standard. RESULTS:
      Using MRI, T-stage, N-stage, and extramural venous invasion were correctly
      predicted for each observer in 90% and 93%, 72% and 69%, and 82% and 78% of
      cases, respectively. With CT the corresponding results were 79% and 76%, 72% and
      72%, 78% and 67%. For MRI inter-observer agreements (Kappa statistics) were 0.79,
      0.10, and 0.76. For CT the corresponding results were 0.64, 0.66, and 0.22.
      CONCLUSION: Patients with locally advanced colon cancer, defined as tumor stage
      T3cd-T4, can be identified by both high resolution MRI and CT, even when CT is
      performed with a metastasis staging protocol. MRI may have an advantage, due to
      its high soft tissue discrimination, to identify certain prognostic factors such
      as T-stage and extramural venous invasion.

PMID- 23550188
TI  - Safety in pediatric imaging: an update.
AB  - Many assumptions are made when imaging children. In particular a judgement is
      made regarding how safe or unsafe each imaging modality is, using relatively
      arbitrary definitions and distinctions, due to the lack of robust scientific
      data. Here, the latest evidence is reviewed, particularly regarding the medical
      exposure to ionizing radiation (X-rays and CT) and MRI in childhood. The best
      evidence currently available suggests a small but convincing risk of cumulative
      low-dose ionizing radiation in children. Given our predictions for the children
      imaged today, it seems reasonable to pursue non-ionizing-based techniques
      wherever possible, although there is emerging evidence that MRI and ultrasound
      may have hitherto unknown effects. As our knowledge base expands, we must
      continually review our practice in light of the latest scientific data. 

PMID- 23550187
TI  - Non-enhanced MR angiography of renal arteries: comparison with contrast-enhanced
      MR angiography.
AB  - BACKGROUND: The main causes of renal artery stenosis (RAS) are atherosclerosis
      and fibromuscular dysplasia. Despite contrast-enhanced magnetic resonance
      angiography (CE-MRA) being a safe and reliable method for diagnosis of RAS
      especially in young individuals, recently it has been possible to adopt
      innovative technologies that do not require paramagnetic contrast agents.
      PURPOSE: To assess the accuracy of steady-state free-precession (SSFP) non
      contrast-enhanced magnetic resonance angiography (NC-MRA) by using a 1.5 T MR
      scanner for the detection of renal artery stenosis, in comparison with breath
      hold CE-MRA as the reference standard. MATERIAL AND METHODS: Sixty-three patients
      (33 men, 30 women) with suspected renovascular hypertension (RVHT) were examined
      by a 1.5T MR scanner; NC-MRA with an electrocardiography (ECG)-gated SSFP
      sequence was performed in 58.7% (37/63) of patients; in 41.3% (26/63) of patients
      a respiratory trigger was used in addition to cardiac gating. CE-MRA, with a
      three-dimensional gradient echo (3D-GRE) T1-weighted sequence, was performed in
      all patients within the same session. Maximum intensity projection (MIP) image
      quality, number of renal arteries, and the presence of stenosis were assessed by
      two observers (independently for NC-MRA and together for CE-MRA). The agreement
      between NC-MRA and CE-MRA as well as the inter-observer reproducibility were
      calculated with Bland-Altman plots. RESULTS: MIP image quality was considered
      better for NC-MRA. NC-MRA identified 143 of 144 (99.3%) arteries detected by CE
      MRA (an accessory artery was not identified). Fourteen stenoses were detected by
      CE-MRA (11 atherosclerotic, 3 dysplastic) with four of 14 (28.5%) significant
      stenosis. Bland-Altman plot demonstrated an excellent concordance between NC-MRA
      and CE-MRA; particularly, the reader A evaluated correctly all investigated
      arteries, while over-estimation of two stenoses occurred for reader B. Regarding
      NC-MRA, inter-observer agreement was excellent. CONCLUSION: NC-MRA is a valid
      alternative to CE-MRA for the assessment of renal arteries.

PMID- 23550189
TI  - Predicting local recurrence following breast-conserving treatment: parenchymal
      signal enhancement ratio (SER) around the tumor on preoperative MRI.
AB  - BACKGROUND: The level of background parenchymal enhancement around tumor is known
      to be associated with breast cancer risk. However, there is no study
      investigating predictive power of parenchymal signal enhancement ratio (SER)
      around tumor for ipsilateral breast tumor recurrence (IBTR). PURPOSE: To
      investigate whether the breast parenchymal SER around the tumor on preoperative
      dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with
      subsequent IBTR in breast cancer patients who had undergone breast-conserving
      treatment. MATERIAL AND METHODS: Nineteen consecutive women (mean age, 44 years;
      range, 34-63 years) with breast cancer who developed IBTR following breast
      conserving treatment and 114 control women matched for age, as well as T and N
      stages were included. We compared the clinicopathologic features of the two
      groups including nuclear grade, histologic grade, hormonal receptor status, human
      epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion,
      negative margin width, use of adjuvant therapy, and parenchymal SER around the
      tumor on preoperative DCE-MRI. The SER was measured on a slice showing the
      largest dimension of the tumor. Multivariate conditional logistic regression
      analysis was used to identify independent factors associated with IBTR. RESULTS:
      In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR
      negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a
      parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with
      IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a
      parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were
      independent factors associated with IBTR. CONCLUSION: In addition to ER
      negativity, a higher parenchymal SER on preoperative MRI was an independent
      factor associated with subsequent IBTR in patients with breast cancer who had
      undergone breast-conserving treatment.

PMID- 23550190
TI  - Detection of Y Chromosome Microdeletion is Valuable in the Treatment of Patients
      With Nonobstructive Azoospermia and Oligoasthenoteratozoospermia: Sperm Retrieval
      Rate and Birth Rate.
AB  - PURPOSE: We evaluated clinical characteristics, sperm retrieval rates, and birth
      rates in a relatively large number of infertile patients with Y chromosome
      microdeletions. MATERIALS AND METHODS: We retrospectively reviewed clinical data
      from 213 patients with nonobstructive azoospermia (NOA) and 76 patients with
      oligoasthenoteratozoospermia (OATS) who were tested for Y chromosome
      microdeletion from March 2004 to June 2011. RESULTS: Of the 289 patients, 110
      patients presented with Y chromosome microdeletion and 179 patients presented
      with no microdeletion. Among the patients with Y chromosome microdeletions,
      83/110 (75.4%) were NOA patients and 27/110 (24.5%) were OATS patients. After
      subdividing the patients with Y chromosome microdeletion, 29 had azoospermia
      factor (AZF)b-c microdeletion and 81 had AZFc microdeletion. The sperm retrieval
      rate was similar between patients with Y chromosome microdeletion and those with
      no microdeletion (26.6% vs. 25.6%, p=0.298) after multiple testicular sperm
      extraction (TESE). Excluding 53 patients who did not undergo TESE, 30 patients
      were analyzed. All of the 9 men with AZFb-c microdeletion had a complete absence
      of sperm despite multiple TESE. However, multiple TESE was successful for 9 of 21
      patients with only AZFc microdeletion (p=0.041). Twenty patients with Y
      chromosome microdeletion gave birth. CONCLUSIONS: In NOA and OATS patients, no
      significant difference in the sperm retrieval rate was shown between patients
      with Y chromosome microdeletion and those with no microdeletion. Patients with
      short Y chromosome microdeletion such as AZFc microdeletion have better prognoses
      for sperm retrieval and an increased chance of conception than do patients with
      larger microdeletions such as AZFb-c microdeletion.

PMID- 23550191
TI  - Survival rate of childhood leukemia in shiraz, southern iran.
AB  - OBJECTIVE: Leukemia is the most prevalent type of cancer in children. The aim of
      this study was to estimate the 5-year survival rates of Acute Lymphoblastic
      Leukemia (ALL) and Acute Myeloblastic Leukemia (AML) as well as factors
      influencing them. METHODS: This is a nonrandomized retrospective study conducted
      on 280 patients with ALL and AML. They were all below 15 years old children
      admitted to Shahid Faghihi hospital, Shiraz, Iran from 2004 to 2008.The survival
      rates were estimated by applying the Kaplan-Meier method. In addition, the log
      rank test was used to estimate the statistical significance of differences in the
      survival probability. Cox regression model was applied to conduct multivariate
      analysis for adjusting confounding variable. All analyses were performed in SPSS
      statistical software (version 16). P-values less than 0.05 were considered as
      statistically significant. FINDINGS: The mean (+/- standard deviation) of the
      observation period was 28.2+/-16.1 months. In this period, 60 (24.7%) patients
      (47 ALL and 15 AML) passed away. The cumulative rate of survival in this study
      was 53.3+/-0.1 percent. This probability was 56.6+/-0.1% and 44.2+/-0.1% for ALL
      and AML patients, respectively, which indicates no statistically significant
      difference between them (P=0.8). According to Cox model, there was a significant
      relationship among the variables of platelet count and relapse with the survival
      rate. CONCLUSION: Platelet count was identified as a positive prognostic factor
      of the survival rate in ALL patients. However, on the base of our results and
      other studies, incidence of relapse and the number of relapses are significant
      factors of survival rates of leukemia.

PMID- 23550192
TI  - Efficacy Evaluation of a New Hyaluronan Derivative HYADD(r) 4-G to Maintain
      Cartilage Integrity in a Rabbit Model of Osteoarthritis.
AB  - Objective: To test the efficacy of a hyaluronan derivative (HYADD(r)4-G) in a
      model of osteoarthritis (anterior cruciate ligament [ACLT]) and to compare its
      efficacy with the injection of growth factors. Design: In a first experimental
      set-up, specially selected for treatment scheme with published studies on
      hyaluronan or growth factor efficacy in osteoarthritis, saline, HYADD(r)4-G, rh
      BMP-7, and the treatments of rh-BMP-7 or rh-BMP-2 with HYADD(r)4-G were injected
      after ACLT, for five times starting 3 weeks after ACLT. Euthanasia was at day 70.
      The knees were evaluated by gross morphological observation, x-ray, and histology
      (Study A). In a second experimental set-up selected to evaluate the efficacy of
      three viscosupplement injections, starting 4 weeks after ACTL, HYADD(r)4-G was
      compared to saline (Study B). Results: (A) X-ray analysis showed more damage in
      the saline group than all other treatment groups (2.67 +/- 0.61 for saline, 0.83
      +/- 0.26 for HYADD(r)4-G, 1.67 +/- 0.82 for HYADD(r)4-G with rh-BMP-2, 0.75 +/-
      0.76 for HYADD(r)4-G with rh-BMP-7, and 1.58 +/- 0.49 for rh-BMP-7), P < 0.05. In
      the femoral condyle, the Mankin's score for HYADD(r)4-G with rh-BMP-2, HYADD(r)4
      G with rh-BMP-7, and rh-BMP7 alone was statistically lower compared to saline in
      the medial part; in the lateral part a significant lower value was observed in
      the HYADD(r)4-G with the rh-BMP-2 group. (B) The Kellgren and Lawrence score and
      Mankin's score was lower in the HYADD(r)4-G group than in the saline group (P <
      0.002 and P = 0.0031). Conclusions: These two studies suggest that HYADD(r)4-G
      delayed the cartilage degeneration and that the association of HYADD(r)4-G with
      growth factors is synergistic.

PMID- 23550193
TI  - Application of sustained delivery microsphere of cyclosporine A for preventing
      posterior capsular opacification in rabbits.
AB  - AIM: To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery
      microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes
      after cataract extraction. METHODS: Twenty New Zealand white rabbits accepted
      cataract extraction plus intraocular lens implantation and their left eyes were
      intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid
      (PLGA) as a carrier and their right eyes were injected with empty MS. The changes
      in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA
      concentration in aqueous humor were examined postoperatively and all the eyes
      were enucleated 3 months after surgery for histopathological and morphological
      examination with light microscopy and electron microscopy. RESULTS: Conjunctival
      hyperemia, corneal edema, intraocular pressure and anterior chamber response of
      experimental and control eyes were similar, while PCO in CsA-MS injected eyes was
      greatly improved compared with that in control eyes. Posterior capsules in CsA-MS
      injected eyes were smooth and lens epithelial cells (LEC) did not proliferate
      significantly (P>0.05), while LEC in posterior capsule of control eyes had
      different degrees of proliferation and cortical regeneration. LEC in CsA-MS
      injected eyes were not functionally active and underwent apoptosis, whereas LEC
      in control eyes were functionally active (F-test, P=0.025). In addition, the
      corneal ultrastructure showed no differences between CsA-MS and MS injected eyes.
      CONCLUSION: CsA-MS has high bioavailability in rabbit eyes and could inhibit
      postoperative PCO occurrence and development during the study period, suggesting
      that CsA-MS may be a promising, effective and safe administration route to
      prevent PCO in clinic.

PMID- 23550194
TI  - Short-Term PCB (Aroclor 1254) Toxicity on Few Phosphatases in Mice Brain.
AB  - The present communication reports the dose and duration dependent toxicity of a
      PCB, Aroclor 1254, to a few ion dependent ATPases, Acid phosphatase, Alkaline
      phosphatase and Glucose-6-phosphatase in the whole brain tissue of mice. Two
      groups of mice were subjected to two sublethal doses (0.1 and 1 mg kgbw(-1) day(
      1)) of PCB orally and exposed for 4, 8 or12 days. A separate control group
      received the corn oil vehicle for the same exposure times. The observed results
      indicated exposure duration dependent changes in the enzymatic levels in the
      brain. The results suggest that the alteration in the enzymatic activity was
      possibly due to imposed oxidative stress generated by Aroclor 1254 on membrane
      bound ion-dependent ATPases and other phosphatases in the brain tissue.

PMID- 23550196
TI  - Paediatric head injuries in the Kwazulu-Natal Province of South Africa: a
      developing country perspective.
AB  - We investigated the causes, management and outcome of head injuries in paediatric
      patients admitted to the paediatric surgery unit at King Edward VIII Hospital
      over a 3-year period, from 1999 to 2001. There were 506 patients (331 male; M:F
      ratio 2:1) and the mean age was 71.99 +36.8 months (2 weeks to 180 months). The
      injuries were due to: motor vehicle crashes (324); falls (121); assault (30);
      inadvertent injury (23); and unknown (11). Forty-nine patients (9%) were admitted
      with a Glasgow Coma Scale <=8. The most common intracranial pathology on computed
      tomography was: intracranial haematoma/haemorrhage (44); contusion (16); and
      brain oedema (10). Nineteen patients (3.4%) underwent neurosurgical intervention
      and the rest were managed conservatively. Eighteen died in hospital (3.6%). The
      mean hospital stay was 5 +/- 12 days. Twenty-three patients (4.5%) were
      discharged with neurological sequelae. Few paediatric patients are admitted with
      severe head injury: the majority from blunt injury caused by motor vehicle
      crashes. Management mainly requires simple neurological observation in a general
      ward with a surprisingly good prognosis. Specific protocols for paediatric head
      injuries have been proposed based on these findings.

PMID- 23550195
TI  - Effect of five-consecutive-day exposure to an anxiogenic stressor on sleep-wake
      activity in rats.
AB  - Repeated exposure to an anxiogenic stressor (AS) is a known environmental factor
      for the development of depression, yet the progression of sleep-wake (S-W)
      changes associated with the onset of AS-induced depression (ASID) is not
      completely understood. Thus, the aim of this study was to identify these
      progressive S-W changes by developing ASID in rats, via repeated exposure to an
      AS, and compare this ASID-associated sleep phenotype with the sleep phenotype of
      human depression. To achieve this aim, rats were first recorded for a 6 h period
      of baseline S-W activity without AS. Then, rats were subjected to 5 days of AS
      [Day 1: inescapable foot-shock; 5 trials of 3 s foot-shocks (1.0 mA) at 3 min
      intervals; Days 3-5: 15 trials of 5 s foot-shocks at 45 s intervals]. S-W
      activity was recorded for 6 h immediately after each AS treatment session. Two
      days later rats were again recorded for 6 h of S-W activity, but with no exposure
      to the AS (NASD). Compared to the baseline day: Day 1 of AS (ASD-1) increased
      wakefulness, slow-wave sleep (SWS) latency, and rapid-eye movement (REM) sleep
      latency, but decreased the total amount of REM sleep; ASD-2 animals remained
      awake throughout the 6 h S-W recording period; ASD-3, ASD-4, and ASD-5 (ASDs-3-5)
      decreased wakefulness, SWS latency, and REM sleep latency, but increased the
      total amount of REM sleep. Interestingly, these results reveal that initial
      exposure to the AS versus later, repeated exposure to the AS produced opposing S
      W changes. On NASD, animals exhibited baseline-like S-W activity, except slightly
      less REM sleep. These results suggest that repeated AS produces a sleep phenotype
      that resembles the sleep phenotype of depression in humans, but consistent re
      exposure to the AS is required. These results are promising because the
      methodological simplicity and reversibility of the ASID-associated S-W phenotype
      could be more advantageous than other animal models for studying the
      pathophysiological mechanisms that underlie the expression of ASID.

PMID- 23550197
TI  - Subacute intestinal obstruction: an enigma revisited.
AB  - Sixty-three patients presenting with subacute intestinal obstruction (SAIO) were
      studied. Thirty (47.6%) reported recurrent symptoms. Exaggerated bowel sound,
      visible/palpable bowel loops, distention of abdomen and abdominal lumps were
      observed in 60.3%, 28.5%, 25.3% and 19.0% patients, respectively. Thirty (47.6%)
      required emergency laparotomy. Investigations revealed lesions requiring surgery
      in 14 of 33 patients which were relieved with conservative treatment. The
      accuracy of ultrasonography, contrast enhanced computed tomography (CECT) scan
      and diagnostic laparoscopy was 57.1%, 100% and 100%, respectively. Ileum was the
      most common site of obstruction (79.5%). Adhesions and small intestinal
      strictures were the two most frequent cause of obstruction seen in 31.8% and
      27.2%, respectively. Tuberculous pathology was demonstrated in 23 (52.2%).
      Previous abdominal surgery was found to be the only predictor of the success of
      conservative treatment (13/19 versus 7/44). All patients of SAIO, whose symptoms
      were relieved with conservative treatment, and who do not have history of
      abdominal surgery, should be subjected to CECT and/or diagnostic laparoscopy in
      order to discover the underlying cause of the obstruction. When these diagnostic
      modalities are not available, laparotomy is an effective alternative for this
      group of patients.

PMID- 23550198
TI  - Antenatal care registration and predicting factors of late registration among
      pregnant women.
AB  - The objective of antenatal care (ANC) is prevention, early recognition and
      treatment of pregnancy related ailments as well as general medical problems. It
      also provides an opportunity for reproductive health counselling. Early
      registration at an antenatal clinic is recommended. However, the majority of
      pregnant women are entered late into an antenatal care programme, especially in
      developing countries such as India. We explored the factors associated with late
      antenatal registration in a rural area of Gujarat State.

PMID- 23550199
TI  - Percutaneous needle aspiration in uncomplicated amebic liver abscess: a
      randomized trial.
AB  - Amoebic liver abscess develops in less than 1% of patients with amoebaisis and
      metronidazole is the drug of choice for the treatment of amebic liver abscess.
      Abscesses of less than 5 cm can be treated with metronidazole alone. However,
      abscesses of more than 10 cm must undergo ultrasound guided percutaneous needle
      aspiration along with metronidazole. The role of percutaneous needle aspiration
      in abscesses of 5 to 10 cm is not clear. Fifty-seven patients with a solitary,
      right lobe, uncomplicated amoebic liver abscess of 5-10 cm were randomized to
      receive either metronidazole alone (control group; n = 29) or ultrasound guided
      percutaneous needle aspiration along with metronidazole (intervention group; n =
      28). Although the resolution of pain and fever occurred earlier in the
      intervention group (27 h and 17 h, respectively) than the control group (48 h and
      30 h, respectively), the difference was not statistically significant (P = 0.16
      and 0.48, respectively). There were no deaths during the study period and
      treatment failure, complications (rupture of abscess), days to normalization of
      leukocytosis and duration of hospitalization were similar in both groups.
      Ultrasound guided percutaneous needle aspiration along with metronidazole was no
      better than metronidazole alone in the management of uncomplicated, solitary,
      right lobe amoebic liver abscess of 5 to 10 cm.

PMID- 23550200
TI  - Peripheral gangrene in Plasmodium vivax malaria: a rare manifestation.
AB  - Symmetrical peripheral gangrene (SPG) is an extremely rare complication of
      malaria that has been well described in multiple case reports of Plasmodium
      falciparum and mixed infection. We present a case of malaria with isolated Pl.
      vivax infection complicated by SPG. This index case is the first reported case of
      peripheral gangrene involving bilateral hands and feet in Pl. vivax infection in
      an adult.

PMID- 23550201
TI  - Lymphatic filariasis elimination programme in Andaman and Nicobar Islands, India:
      drug coverage and compliance post eight rounds of MDA.
AB  - Lymphatic filariasis (LF) is endemic in the Andaman and Nicobar islands,
      including the lone foci for a diurnally sub-periodic form of Wuchereria bancrofti
      in the Nancowry group of islands. A programme to eliminate LF was launched in
      2004 by the Directorate of Health Services, Andaman and Nicobar Administration
      which involved a single annual mass drug administration (MDA) using
      diethylcarbamazine (DEC) with albendazole. So far, eight rounds of MDA have been
      implemented through the Public Health Care network. The pattern of antifilarial
      drug distribution and compliance achieved in the on-going LF elimination
      programme in these islands has been assessed. This is the first systematic effort
      undertaken in these remote islands to assess the coverage and compliance with the
      LF elimination programme. This study covered 900 households in each of the 3
      districts. There were a largest number of side effects in the Nicobar district
      (6.4%). Non-consumption of drugs ranged from 18.6% (Nicobar) to 42% (North and
      Middle Andaman). A survey revealed that almost 95.3% of the respondents had heard
      about MDA from the drug distributors. Therefore, the distributors should be
      involved in programmes designed to educate the community at risk of acquiring
      filarial infection and the possible side effects of the drugs.

PMID- 23550202
TI  - Fabrication of autoclavable bacteriologic loops for handling Mycobacterium
      tuberculosis isolates from recycled materials in a resource poor setting.
AB  - In resource limited settings, the appropriation of scarce resources during
      research efforts can be daunting. Sourcing for disposable plastic bacteriological
      loops for manipulating M. tuberculosis had been eating into the research budget.
      In an attempt to reduce cost, an alternative and more cost effective way of
      obtaining autoclavable bacteriologic inoculation loops from used materials in the
      laboratory was employed. Autoclave resistant loops were prepared from
      polypropylene automatic pipette tips and platinum wires from electric stoves. The
      loop volume, when desired, was calculated using a simple mathematical equation
      after several passes in weighted water. Laboratories in resource poor settings
      could also save on inoculating loops by adopting such pragmatic approaches using
      recycled materials.

PMID- 23550203
TI  - Pyopericardium complicated with cardiac tamponade: an unusual presenting
      manifestation of primary pyomyositis.
AB  - Primary pyomyositis is an infective condition mainly involving the skeletal
      muscles. Various cardiac complications reported are acute bacterial endocarditis,
      pyogenic pericarditis, pancarditis and, very rarely, pyopericardium presenting as
      cardiac tamponade. We report a case of 15-year-old boy presenting with complaints
      of fever, progressive shortness of breath and retrosternal pleuritic chest pain.
      He also complained of painful swellings of left arm, left side of neck and left
      thigh extending up to the knee joint. Ultrasonography showed collections in the:
      bilateral sternocleidomastoid; subclavius; left thigh muscles; and left knee
      joint. Echocardiography showed evidence of cardiac tamponade. He underwent
      emergent pericardiocentesis and frank pus was drained. Pus culture grew
      Methicillin resistant Staphylococcous aureus. With drainage and the appropriate
      antibiotics, he improved.

PMID- 23550204
TI  - Pure cerebellitis due to scrub typhus: a unique case report.
AB  - We report the case of a 24-year old Indian man who presented with: high fever;
      drowsiness; an eschar and gross cerebellar dysfunction with horizontal gaze
      nystagmus; ataxic speech; and truncal ataxia. Scrub typhus was diagnosed by
      serological tests. This is the first case of a pure cerebellar involvement as the
      only manifestation of scrub typhus in the published literature.

PMID- 23550205
TI  - Microbiological characteristics of acute prostatitis after transrectal prostate
      biopsy.
AB  - PURPOSE: We aimed to identify microbiological characteristics in patients with
      acute prostatitis after transrectal prostate biopsy to provide guidance in the
      review of prevention and treatment protocols. MATERIALS AND METHODS: A
      retrospective analysis of medical records was performed in 1,814 cases who
      underwent prostate biopsy at Seoul St. Mary's Hospital and St. Vincent's Hospital
      over a 5 year period from 2006 to 2011. Cases in which acute prostatitis occurred
      within 7 days after the biopsy were investigated. Before starting treatment with
      antibiotics, sample collections were done for culture of urine and blood. Culture
      and drug susceptibility was identified by use of a method established by the
      Clinical and Laboratory Standards Institute. RESULTS: A total of 1,814 biopsy
      procedures were performed in 1,541 patients. For 1,246 patients, the procedure
      was the first biopsy, whereas for 295 patients it was a repeat biopsy. Twenty-one
      patients (1.36%) were identified as having acute bacterial prostatitis after the
      biopsy. Fifteen patients (1.2%) had acute prostatitis after the first biopsy, and
      6 patients (2.03%) experienced acute prostatitis after a repeat biopsy. Even
      though the incidence of acute bacterial prostatitis was higher after repeat
      biopsy than that after the first biopsy, there was no statistically significant
      intergroup difference in terms of incidence (chi(2)=1.223, p=0.269). When the
      collected urine and blood samples were cultured, Escherichia coli was found in
      samples from 15 patients (71.4%), Klebsiella pneumoniae in 3 patients (14.3%),
      Enterobacter intermedius in 1 patient (4.8%), E. aerogenes in 1 patient (4.8%),
      and Pseudomonas aeruginosa in 1 patient (4.8%). A fluoroquinolone-resistant
      strain was confirmed in 5 cases (23.8%) in total. Three cases of E. coli and 1
      case of Klebsiella had extended-spectrum beta-lactamase activity. CONCLUSIONS:
      Empirical treatment of acute prostatitis should be done with consideration of
      geographical prevalence and drug resistance. This study will provide meaningful
      information for the management of acute prostatitis after transrectal prostate
      biopsy.

PMID- 23550206
TI  - Vascular graft thrombosis secondary to activated protein C resistance: a case
      report and literature review.
AB  - Hypercoagulability is a well-documented and prominent risk factor for venous
      thromboembolism. The role of thrombophilia in arterial thrombotic events is less
      well defined. A 52-year-old male patient with multiple atherogenic risk factors
      was admitted for non-healing pedal ulcer and absent distal pulses. Based on the
      clinical presentation, Doppler ultrasound and angiography findings, the patient
      underwent elective in situ bypass arterial reconstruction. The saphenous vein
      graft was of satisfactory quality and the procedure went routinely. Acute graft
      thrombosis on postoperative day 0 was recognized immediately and prompted an
      emergent surgical revision. No technical errors or anatomical/mechanical causes
      for failed reconstruction were found and the graft was successfully
      thrombectomized using a Fogarty balloon-catheter. Graft rethrombosis, however,
      ensued after several hours. Considering the absence of threatening limb ischemia
      and the idiopathic recurrent thrombosis, raising suspicion of prothrombotic
      state, conservative treatment was pursued. Postoperative thrombophilia testing
      proved positive for activated protein C resistance, mandating introduction of
      chronic oral anticoagulation. Six months later, the operated extremity is viable.
      Inexplicable vascular graft thrombosis, particularly if early and recurrent,
      should raise suspicion of underlying thrombophilia. If confirmed by laboratory
      testing, long-term secondary antithrombotic prophylaxis may be required. 

PMID- 23550207
TI  - Influence of the chronic abdominal aortic occlusion on the femoral artery disease
      pattern.
AB  - We design a study to evaluate whether patients with chronic aortic occlusion have
      a different pattern of femoral artery atherosclerosis than patients with other
      forms of aortoiliac disease as well as to discuss potential causal mechanisms.
      From January 2008 to January 2010, 467 patients with aortoiliac occlusive disease
      were enrolled at Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia.
      Among them 60 patients were divided into two groups, patients with chronic aortic
      occlusion (COA) and diffuse aortoiliac occlusive disease (AIOD, Leriche type II).
      Each group consisted of 30 patients. Those two groups were compared according to
      symptomatology, ABI values, femoral artery pressure gradient, atherosclerosis
      level in the femoral region and predictors of atherosclerosis.Patients with AIOD
      had severe atherosclerosis unlike patients with COA. Also, high elevation of
      postoperative ABIs in patients with an early atherosclerosis (0, I, II and III)
      was noted suggesting patent distal arterial tree. FAP gradient was significantly
      higher in COA group comparing with AIOD group (left: t=-10.963, P<0.01;right: t=
      8.962, P<0.01). In conclusion, our data demonstrate that older patients have had
      more time to develop multilevel disease (AOID) and those with CAO have more
      isolated aortic disease chronic aortic occlusion.

PMID- 23550208
TI  - Prevalence of nocturnal enuresis in school aged children: the role of personal
      and parents related socio-economic and educational factors.
AB  - OBJECTIVE: Nocturnal enuresis is a common psychosocial concern for both parents
      and children. In the present study we have determined the prevalence of nocturnal
      enuresis in Urmia, Iran children and associated personal and familial factors
      with this problem. METHODS: A cross sectional epidemiological study for detection
      of nocturnal enuresis prevalence rate and evaluation of associated familial and
      personal factors in elementary school children (7-11 years old) from Urmia were
      investigated. The subjects were selected by cluster sampling method. Chi square
      test and logistic regression were used in univariate and multivariate
      respectively. FINDINGS: Of the 1600 questionnaires distributed, 918 (57%) were
      completed and included in the final analysis. The rest, which were not filled by
      parents and also those out of our study age range were excluded. Gender of the
      subjects was almost equally distributed (48.6% males and 51.4% females).
      Prevalence of nocturnal enuresis was 18.7% (n = 172) and prevalence of day time
      incontinence was 5.5% (n=51). There was no significant gender difference between
      these two groups. Enuretics had crowded families, positive family history, low
      educational level of parents, jobless father, working mother, single parent, poor
      school performance, positive history of urinary tract infection (UTI).
      CONCLUSION: Our results with enuresis prevalence and associated factors were
      comparable to other epidemiological studies from various countries. We found that
      Iranian families do not pay sufficient attention to their enuretic children.

PMID- 23550209
TI  - The scientific drunk and the lamppost: massive sequencing efforts in cancer
      discovery and treatment.
AB  - The massive resources devoted to genome sequencing of human tumors have produced
      important data sets for the cancer biology community. Paradoxically, however,
      these studies have revealed very little new biology. Despite this, additional
      resources in the United States are slated to continue such work and to expand
      similar efforts in genome sequencing to mouse tumors. It may be that scientists
      are "addicted" to the large amounts of data that can be relatively easily
      obtained, even though these data seem unlikely, on their own, to unveil new
      cancer treatment options or result in the ultimate goal of a cancer cure. Rather
      than using more tumor genetic sequences, a better strategy for identifying new
      treatment options may be to develop methods for analyzing the signaling networks
      that underlie cancer development, progression, and therapeutic resistance at both
      a personal and systems-wide level.

PMID- 23550210
TI  - Integrative analysis of complex cancer genomics and clinical profiles using the
      cBioPortal.
AB  - The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web
      resource for exploring, visualizing, and analyzing multidimensional cancer
      genomics data. The portal reduces molecular profiling data from cancer tissues
      and cell lines into readily understandable genetic, epigenetic, gene expression,
      and proteomic events. The query interface combined with customized data storage
      enables researchers to interactively explore genetic alterations across samples,
      genes, and pathways and, when available in the underlying data, to link these to
      clinical outcomes. The portal provides graphical summaries of gene-level data
      from multiple platforms, network visualization and analysis, survival analysis,
      patient-centric queries, and software programmatic access. The intuitive Web
      interface of the portal makes complex cancer genomics profiles accessible to
      researchers and clinicians without requiring bioinformatics expertise, thus
      facilitating biological discoveries. Here, we provide a practical guide to the
      analysis and visualization features of the cBioPortal for Cancer Genomics.

PMID- 23550212
TI  - The switches.ELM resource: a compendium of conditional regulatory interaction
      interfaces.
AB  - Short linear motifs (SLiMs) are protein interaction sites that play an important
      role in cell regulation by controlling protein activity, localization, and local
      abundance. The functionality of a SLiM can be modulated in a context-dependent
      manner to induce a gain, loss, or exchange of binding partners, which will affect
      the function of the SLiM-containing protein. As such, these conditional
      interactions underlie molecular decision-making in cell signaling. We identified
      multiple types of pre- and posttranslational switch mechanisms that can regulate
      the function of a SLiM and thereby control its interactions. The collected
      examples of experimentally characterized SLiM-based switch mechanisms were
      curated in the freely accessible switches.ELM resource
      (http://switches.elm.eu.org). On the basis of these examples, we defined and
      integrated rules to analyze SLiMs for putative regulatory switch mechanisms. We
      applied these rules to known validated SLiMs, providing evidence that more than
      half of these are likely to be pre- or posttranslationally regulated. In
      addition, we showed that posttranslationally modified sites are enriched around
      SLiMs, which enables cooperative and integrative regulation of protein
      interaction interfaces. We foresee switches.ELM complementing available resources
      to extend our knowledge of the molecular mechanisms underlying cell signaling.

PMID- 23550211
TI  - Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription
      and cell death.
AB  - The tumor suppressor protein p53 is a critical stress response transcription
      factor that induces the expression of genes leading to cell cycle arrest,
      apoptosis, and tumor suppression. We found that mammalian inositol polyphosphate
      multikinase (IPMK) stimulated p53-mediated transcription by binding to p53 and
      enhancing its acetylation by the acetyltransferase p300 independently of its
      inositol phosphate and lipid kinase activities. Genetic or RNA interference
      (RNAi)-mediated knockdown of IPMK resulted in decreased activation of p53,
      decreased recruitment of p53 and p300 to target gene promoters, abrogated
      transcription of p53 target genes, and enhanced cell viability. Additionally,
      blocking the IPMK-p53 interaction decreased the extent of p53-mediated
      transcription. These results suggest that IPMK acts as a transcriptional
      coactivator for p53 and that it is an integral part of the p53 transcriptional
      complex facilitating cell death.

PMID- 23550213
TI  - DNA damage response in male gametes of Cyrtanthus mackenii during pollen tube
      growth.
AB  - Male gametophytes of plants are exposed to environmental stress and mutagenic
      agents during the double fertilization process and therefore need to repair the
      DNA damage in order to transmit the genomic information to the next generation.
      However, the DNA damage response in male gametes is still unclear. In the present
      study, we analysed the response to DNA damage in the generative cells of
      Cyrtanthus mackenii during pollen tube growth. A carbon ion beam, which can
      induce DNA double-strand breaks (DSBs), was used to irradiate the bicellular
      pollen, and then the irradiated pollen grains were cultured in a liquid culture
      medium. The male gametes were isolated from the cultured pollen tubes and used
      for immunofluorescence analysis. Although inhibitory effects on pollen tube
      growth were not observed after irradiation, sperm cell formation decreased
      significantly after high-dose irradiation. After high-dose irradiation, the cell
      cycle progression of generative cells was arrested at metaphase in pollen mitosis
      II, and phosphorylated H2AX (gammaH2AX) foci, an indicator of DSBs, were detected
      in the majority of the arrested cells. However, these foci were not detected in
      cells that were past metaphase. Cell cycle progression in irradiated generative
      cells is regulated by the spindle assembly checkpoint, and modification of the
      histones surrounding the DSBs was confirmed. These results indicate that during
      pollen tube growth generative cells can recognize and manage genomic lesions
      using DNA damage response pathways. In addition, the number of generative cells
      with gammaH2AX foci decreased with culture prolongation, suggesting that the DSBs
      in the generative cells are repaired.

PMID- 23550214
TI  - Conflicts of interest and clinical recommendations: comparison of two concurrent
      clinical practice guidelines for primary immune thrombocytopenia developed by
      different methods.
AB  - The growing influence of practice guidelines has increased concern for potential
      sources of bias. Two recent guidelines for primary immune thrombocytopenia (ITP)
      provided a unique opportunity for a systematic comparison of different methods of
      practice guideline development. One guideline (International Consensus Report
      [ICR]) was supported by pharmaceutical companies that produce products for ITP.
      The ICR panel members were selected for expertise in ITP; 16 (73%) reported
      associations with pharmaceutical companies. The other guideline was sponsored by
      the American Society of Hematology (ASH); panel members were selected for lack of
      conflicts and for expertise in guideline development as well as for ITP.
      Discrepancies were conspicuous when the guidelines addressed treatment. In
      contrast to the ASH guideline, the ICR gave stronger recommendations for agents
      manufactured by companies from which the ICR or its panel members received
      support. These data provide direct evidence that differences in financial support
      and methods of evidence evaluation can influence recommendations. 

PMID- 23550215
TI  - Residents examine factors associated with 30-day, same-cause hospital
      readmissions on an internal medicine service.
AB  - In recent years, there has been increased interest in stemming the tide of
      hospital readmissions in an attempt to improve quality of care. This study
      presents the Phase I results of a resident-led quality improvement initiative to
      determine the percentage of and risk factors for same-cause readmissions (SCRs;
      defined as hospital readmission within 30 days of hospital discharge for
      treatment of the same condition) to the internal medicine service of a
      multispecialty teaching hospital in central Texas. Results indicate that patients
      diagnosed with chronic obstructive pulmonary disease/asthma or anemia may be at
      increased risk for SCRs. Those patients who are insured by Medicaid and those who
      require assistance from social services also demonstrated an increased risk for
      SCRs. This study appears to be the first resident-led initiative in the field to
      examine 30-day SCRs to an internal medicine service for demographic and clinical
      risk factors. 

PMID- 23550216
TI  - Inhibition of RhoA/Rho-kinase pathway suppresses the expression of extracellular
      matrix induced by CTGF or TGF-beta in ARPE-19.
AB  - AIM: To investigate the role of Rho-associated protein kinase (ROCK) inhibitor,
      Y27632, in mediating the production of extracellular matrix (ECM) components
      including fibronectin, matrix metallo-proteinase-2 (MMP-2) and type I collagen as
      induced by connective tissue growth factor (CTGF) or transforming growth factor
      beta (TGF-beta) in a human retinal pigment epithelial cell line, ARPE-19.
      METHODS: The effect of Y27632 on the CTGF or TGF-beta induced phenotype in ARPE
      19 cells was measured with immunocytochemistry as the change in F-actin. ARPE-19
      cells were treated with CTGF (1, 10, 100ng/mL) and TGF-beta (10ng/mL) in serum
      free media, and analyzed for fibronectin, laminin, and MMP-2 and type I collagen
      by RT-qPCR and immunocytochemistry. Cells were also pretreated with an ROCK
      inhibitor, Y27632, to analyze the signaling contributing to ECM production.
      RESULTS: Treatment of ARPE-19 cells in culture with TGF-beta or CTGF induced an
      ECM change from a cobblestone morphology to a more elongated swirl pattern
      indicating a mesenchymal phenotype. RT-qPCR analysis and different gene
      expression analysis demonstrated an upregulation in expression of genes
      associated with cytoskeletal structure and motility. CTGF or TGF-beta
      significantly increased expression of fibronectin mRNA (P=0.006, P=0.003
      respectively), laminin mRNA (P=0.006, P=0.005), MMP-2 mRNA (P= 0.006, P= 0.001),
      COL1A1 mRNA (P=0.001, P=0.001), COL1A2 mRNA (P=0.001, P=0.001). Preincubation of
      ARPE-19 with Y27632 (10mmol/L) significantly prevented CTGF or TGF- beta induced
      fibronectin (P=0.005, P=0.003 respectively), MMP-2 (P= 0.003, P=0.002), COL1A1
      (P=0.006, P=0.003), and COL1A2 (P=0.006, P=0.004) gene expression, but not
      laminin (P=0.375, P=0.516). CONCLUSION: Our study demonstrated that both TGF-beta
      and CTGF upregulate the expression of ECM components including fibronectin,
      laminin, MMP-2 and type I collagen by activating the RhoA/ROCK signaling pathway.
      During this process, ARPE-19 cells were shown to change from an epithelial to a
      mesenchymal phenotype in vitro. Y27632, a ROCK inhibitor, inhibited the
      transcription of fibronectin, MMP-2 and type I collagen, but not laminin. The
      data from our work suggest a role for CTGF as a profibrotic mediator. Inhibiting
      the RhoA/ROCK pathway represents a potential target to prevent the fibrosis of
      RPE cells. This might lead to a novel therapeutic approach to preventing the
      onset of early PVR.

PMID- 23550217
TI  - First generation stochastic gene episilencing (step1) model and applications to
      in vitro carcinogen exposure.
AB  - A novel first-generation stochastic gene episilencing (STEP1) model is introduced
      for quantitatively characterizing the probability of in vitro epigenetically
      silencing (episilencing) specific tumor-suppressor-microRNA (miRNA) genes by
      carcinogen exposure. Although the focus is mainly on in-vitro exposure of human
      cells to ionizing radiation, the mathematical formulations presented are general
      and can be applied to other carcinogens. With the STEP1 model, a fraction fj of
      the surviving target cells can have their tumor-suppressor-miRNA gene of type j
      silenced while the remaining fraction, 1 - fj , of the surviving cells do not
      undergo gene episilencing. Suppressor gene episilencing is assumed to arise as a
      Poisson process characterized with and exponential distribution of episilencing
      doses with mean dj . In addition to providing mathematical functions for
      evaluating the single-target-gene episilencing probability, functions are also
      provided for the multi-target-gene episilencing probability for simultaneously
      silencing of multiple tumor-suppressor-miRNA genes. Functional relationships are
      first developed for moderate doses where adaptive responses are unlikely and are
      then modified for low doses where adaptation can occur. Results apply to a
      specific follow-up time t after carcinogen exposure that exceeds the maximum time
      for the occurrence of an induced episilencing event.

PMID- 23550219
TI  - Feasibility of the Interferon-gamma Release Assay for the Diagnosis of
      Genitourinary Tuberculosis in an Endemic Area.
AB  - PURPOSE: To evaluate the feasibility of the interferon-gamma release assay (IGRA)
      as a supplementary diagnostic tool for the diagnosis of genitourinary
      tuberculosis (GUTB). MATERIALS AND METHODS: Fifty-seven patients who were tested
      with the IGRA to diagnose GUTB were included. All patients had clinical or
      radiologic features suspicious for GUTB. Signs and symptoms included chronic
      dysuria with long-standing sterile pyuria, renal calcification with distorted
      renal calyces and contracted renal pelvis, and chronic epididymitis. Patients who
      had a history of tuberculosis in other organs were excluded. Tests including
      IGRA, urine acid-fast bacilli (AFB) stain and culture, urine tuberculosis
      polymerase chain reaction (UT-PCR), and radiological examinations were performed
      to confirm GUTB. The medical records of the patients were reviewed
      retrospectively. RESULTS: The IGRA result was positive in 30 patients (52.6%).
      The results of the urine AFB stain and culture were positive in 5 patients (8.8%)
      and 7 patients (12.2%), respectively. The results of UT-PCR were positive in 9
      patients (15.8%). The 7 patients who showed positive results in the urine AFB
      stain and culture also had positive results on the IGRA. A UT-PCR-negative
      patient was diagnosed with GUTB by positive results on both the IGRA and AFB
      stain and culture. CONCLUSIONS: The IGRA might feasibly be used as a
      supplementary or screening tool for the diagnosis of GUTB in addition to urine
      AFB stain and culture. Further studies for statistical evaluation of its
      sensitivity, specificity, and efficacy are needed.

PMID- 23550221
TI  - Effect of Y-27632 on the cultured retinal neurocytes of rats.
AB  - AIM: To investigate the effect of Y-27632 on the survival and neurite outgrowth
      of the cultured retinal neurocytes. METHODS: After the postnatal day 2-3, Sprague
      Dawley retinal neurocytes were cultured for 48 hours, the culture media was
      replaced with serum-free media (control group) and serum-free media contained
      30umol/L Y-27632 (Y-27632 group), and the cells were continually cultured another
      48 hours. The cultured retinal neurocytes were identified with anti-neuron
      specific enolase (NSE) immunocytochemistry. The survival state of those cells was
      estimated by MTT assay, and the neurite outgrowth of those cells was evaluated by
      the computerized image-analysis system. RESULTS: Compared with the control group,
      the absorbance values of cells survival in Y-27632 group increased 12.90% and
      33.33% respectively after 72 and 96 hours culture. Y-27632 had no significant
      effect on the diameter of cultured retinal neurocytes. Compared with the control
      group, Y-27632 induced a stable improvement of neurite outgrowth of retinal
      neurocytes after 72 and 96 hours culture (P=0.001). CONCLUSION: Y-27632 could
      promote the survival and neurite outgrowth of the early postnatal cultured
      retinal neurocytes.

PMID- 23550220
TI  - Paucity of intrahepatic bile ducts in neonates: the first case series from iran.
AB  - OBJECTIVE: Paucity of interlobular bile ducts (PIBD), defined as absence or
      marked decrease in the number of interlobular bile ducts, is one of the causes of
      neonatal cholestasis. Treatment includes treating the intractable pruritus caused
      by persistent cholestasis. PIBD can be part of a familial syndrome of cholestasis
      named Alagille syndrome (AGS). We report clinical status of a case series of
      Iranian patients with PIBD. METHODS: In this retrospective study, patients with
      cholestasis admitted to the pediatric gastroenterology ward in a referral
      hospital in Shiraz from January 2006 to January 2010 and underwent liver biopsy
      were evaluated. Clinical and paraclinical status of children with the pathologic
      diagnosis of PIBD was assessed. FINDINGS: Disease was presented in all jaundiced
      patients with aged in average 3 days at presentation. Seven patients had the
      criteria of AGS. Despite medical treatment, cholestasis was not controlled in 6
      (28.6%) patients. Liver transplantation led to the survival of 5 patients while
      the other patient who did not undergo liver transplantation died at 2 months of
      age. One patient underwent peritoneal dialysis due to renal insufficiency and
      died at 9 months of age. After 1-5 years of follow-up, the mortality rate was
      9.5%. CONCLUSION: In patients with intractable cholestasis, only patients that
      underwent liver transplantation survived. Thus, the most important criterion for
      liver transplantation in neonatal PIBD is intractable cholestasis. This is the
      first report that shows AGS can result in neonatal-onset renal insufficiency.

PMID- 23550218
TI  - CNS control of glucose metabolism: response to environmental challenges.
AB  - Over the last 15 years, considerable work has accumulated to support the role of
      the CNS in regulating postprandial glucose levels. As discussed in the first
      section of this review, the CNS receives and integrates information from afferent
      neurons, circulating hormones, and postprandially generated nutrients to
      subsequently direct changes in glucose output by the liver and glucose uptake by
      peripheral tissues. The second major component of this review focuses on the
      effects of external pressures, including high fat diet and changes to the
      light:dark cycle on CNS-regulating glucose homeostasis. We also discuss the
      interaction between these different pressures and how they contribute to the
      multifaceted mechanisms that we hypothesize contribute to the dysregulation of
      glucose in type 2 diabetes mellitus (T2DM). We argue that while current
      peripheral therapies serve to delay the progression of T2DM, generating combined
      obesity and T2DM therapies targeted at the CNS, the primary site of dysfunction
      for both diseases, would lead to a more profound impact on the progression of
      both diseases.

PMID- 23550222
TI  - Dose Response of MTLn3 Cells to Serial Dilutions of Arsenic Trioxide and Ionizing
      Radiation.
AB  - MTLn3 cells derived from mouse mammary epithelium are known to be highly
      malignant and are resistant to both radio- and chemo-therapy. We exposed MTLn3
      cells to various doses of inorganic Arsenic trioxide (As2O3) in combination with
      ionizing radiation. Cells were treated with a series of As2O3 concentrations
      ranging from 20 MUM to 1.22 nM for 8 hour, 24 hour and 48 hour periods. Post
      treated cell proliferation was quantified by measuring mitochondrial activity and
      DNA analysis. Cells exposed to radiation and As2O3 at concentration greater than
      1.25 MUM showed apoptosis and radiations alone treated cells were statistically
      not different from the control. Hormesis was observed for As2O3 concentrations in
      the range of 0.078 MUM to 0.625 MUM while the combined chemo and radiation
      treatments of the cells did not affect the hormetic effect. We have demonstrated
      that As2O3 (in the presence and absence of ionizing radiation) in specific low
      concentrations induced apoptosis in the otherwise chemoresistant cancer cells.
      This low concentration-mediated cell death is immediately followed by a surge in
      cell survival. Low dosing dosimetry is highly desirable in metronomic therapy
      however, it has a narrow window since necrosis, hormesis, apoptosis and other
      dose-dependent biological processes take place in this region. Further
      quantifiable dosimetry is highly desired for routine clinical practice.

PMID- 23550223
TI  - Parent and physician perspectives on the treatment of primary nocturnal enuresis
      in Korea.
AB  - PURPOSE: Parental decisions about the treatment of nocturnal enuresis (NE) are
      generally based on silent agreement with a physician's recommendation. However,
      physicians may have an insufficient understanding about parents' concerns and
      expectations regarding treatment. The aim of this study was to clarify the
      discrepancies between the perceptions of parents and physicians and to better
      understand the attitudes related to NE treatment. MATERIALS AND METHODS: A survey
      was conducted in six centers and included 105 parents and 102 physicians. Two
      questionnaires, one for parents and another for physicians, were prepared. Each
      contained items on demographic characteristics, concerns, and NE treatment
      preferences. The parents completed the questionnaire during their child's first
      clinical visit, and the physicians completed the questionnaire via e-mail or
      individual interviews. RESULTS: Low self-esteem was the most common concern among
      both parents and physicians. Parents showed a more serious concern regarding
      disease progression and sequelae than did physicians. In the parent group,
      parents of younger children were mainly concerned about growth, whereas parents
      of children with daytime symptoms were mainly concerned about disease progression
      and relationships. Treatment outcome preferences differed significantly between
      the two groups. Physicians preferred treatments yielding immediate results,
      whereas parents preferred long-term treatments that would result in low
      recurrence. CONCLUSIONS: This survey presents the differences between parents and
      physicians regarding NE concerns and therapeutic preferences. Our study may
      provide valuable insight for physicians regarding parental attitudes toward NE
      treatment.

PMID- 23550224
TI  - The effect of nicotinamide on gene expression in a traumatic brain injury model.
AB  - Microarray-based transcriptional profiling was used to determine the effect of
      nicotinamide on gene expression in an experimental traumatic brain injury (TBI)
      model. Ingenuity Pathway Analysis (IPA) was used to evaluate the effect on
      relevant functional categories and canonical pathways. At 24 h, 72 h, and 7 days,
      respectively, 70, 58, and 76%, of the differentially expressed genes were up
      regulated in the vehicle treated compared to the sham animals. At 24 h post-TBI,
      there were 150 differentially expressed genes in the nicotinamide treated animals
      compared to vehicle; the majority (82%) down-regulated. IPA analysis identified a
      significant effect of nicotinamide on the functional categories of cellular
      movement, cell-to-cell-signaling, antigen presentation and cellular compromise,
      function, and maintenance and cell death. The canonical pathways identified were
      signaling pathways primarily involved with the inflammatory process. At 72 h post
      cortical contusion injury, there were 119 differentially expressed genes in the
      nicotinamide treated animals compared to vehicle; the majority (90%) was up
      regulated. IPA analysis identified a significant effect of nicotinamide on cell
      signaling pathways involving neurotransmitters, neuropeptides, growth factors,
      and ion channels with little to no effect on inflammatory pathways. At 7 days
      post-TBI, there were only five differentially expressed genes with nicotinamide
      treatment compared to vehicle. Overall, the effect of nicotinamide on
      counteracting the effect of TBI resulted in significantly decreased number of
      genes differentially expressed by TBI. In conclusion, the mechanism of the effect
      of nicotinamide on secondary injury pathways involves effects on inflammatory
      response, signaling pathways, and cell death.

PMID- 23550225
TI  - Inequality in School Readiness and Autism among 6-Year-Old Children across
      Iranian Provinces: National Health Assessment Survey Results.
AB  - OBJECTIVE: To assess the national inequality of school readiness and autism among
      6-year-old Iranian children before school entry using a national health
      assessment survey. METHODS: In a cross-sectional nationwide survey, all Iranian
      children entering public and private elementary schools were asked to participate
      in a mandatory national screening program in Iran in 2009 in two levels of
      screening and diagnostic levels. FINDINGS: The study population consisted of
      955388 children (48.5% girls and 76.1% urban residents). Of the whole children,
      3.1% of the 6-year-old children had impaired vision. In addition, 1.2, 1.8, 1.4,
      7.6, 0.08, 10, 10.9, 56.7, 0.7, 0.8 and 0.6 percent had color blindness, hearing
      impaired, speech disorder, school readiness, autism, height to age retardation,
      body mass index extremes, decayed teeth, disease with special needs, spinal
      disorders, and hypertension, respectively. The distribution of these disorders
      was unequally distributed across provinces. CONCLUSION: Our results confirmed
      that there is an inequality in distribution of school readiness and autism in 6
      year-old children across Iranian provinces. The observed burden of these
      distributions among young children needs a comprehensive national policy with
      evidence-based province programs to identify the reason for different inequality
      among provinces.

PMID- 23550226
TI  - Regulation of interleukin 33/ST2 signaling of human corneal epithelium in
      allergic diseases.
AB  - AIM: To identify the function of ST2 and explore the role of IL-33/ST2 signaling
      in regulating the pro-allergic cytokine production in human corneal epithelial
      cells (HCECs). METHODS: Human corneal tissues and cultured primary HCECs were
      treated with IL-33 in different concentrations without or with different
      inhibitors to evaluate the expression, location and signaling pathways of ST2 in
      regulating production of pro-allergic cytokine and chemokine. The expression of
      mRNA was determined by reverse transcription and real time PCR, and protein
      production was measured by enzyme-linked immunosorbent assay (ELISA),
      immunohistochemical and immunofluorescent staining. ST2 protein was detected in
      donor corneal epithelium, and ST2 signal was enhanced by exposure to IL-33.
      RESULTS: IL-33 significantly stimulated production of pro-allergic cytokines
      thymic stromal lymphopoietin (TSLP) and chemokine (CCL2, CCL20, CCL22) in HCECs
      at both mRNA and protein levels. These stimulated productions of pro-allergic
      mediators by IL-33 were blocked by ST2 antibody or soluble ST2 protein (P<0.05).
      Interestingly, the IkappaB-alpha inhibitor BAY11-7082 or NF-kappaB activation
      inhibitor quinazoline blocked NF-kappaB p65 protein nuclear translocation, and
      also suppressed the productions of these pro-allergic cytokines and chemokine
      induced by IL-33. CONCLUSION: These findings demonstrate that IL-33/ST2 signaling
      plays an important role in regulating IL-33 induced pro-allergic responses. IL-33
      and ST2 could become novel molecular targets for the intervention of allergic
      diseases in ocular surface.

PMID- 23550227
TI  - Land elevation and cancer mortality in u.s. Cities and counties using median
      elevations derived from geographic information systems.
AB  - There are a number of variables that are correlated with land elevation. Land
      elevation, and in particular, its surrogate variables such as natural background
      radiation, can be studied in relation to cancer rates. The present ecological
      study focuses on three such variables correlated with land elevation: natural
      background radiation (NBR), oxygen concentration (OC), and barometric pressure
      (BP). In addition, the study uses a novel approach for determining median land
      elevation values from which the surrogated variables are estimated. Inverse
      correlations were observed for NBR while direct correlations were found for OC
      and BP suggesting the presence of a protective effect with all three variables.
      Further study is indicated to either verify or refute these findings.

PMID- 23550228
TI  - Acute epididymitis in children: the role of the urine test.
AB  - PURPOSE: Acute epididymitis is considered to have an important role in children
      with scrotal pain. Recent reports have shown that urinalysis is not helpful for
      the diagnosis and treatment of acute epididymitis owing to negative
      microbiological findings. Therefore, we analyzed clinical and laboratory
      characteristics to examine the diagnostic yield of urinalysis in children.
      MATERIALS AND METHODS: We retrospectively reviewed the medical records of 139
      patients who were diagnosed with acute epididymitis from 2005 to 2011. Diagnosis
      was based on symptoms, physical findings, and color Doppler ultrasonography
      (DUS). To investigate the characteristics of epididymitis in children, the
      patients were divided into 3 groups: group A (aged less than 18 years, 76
      patients), group B (18 to 35 years old, 19 patients), and group C (older than 35
      years, 44 patients). RESULTS: There were statistically significant differences in
      age, symptom duration, hospital stays, and lesion location in each group. White
      blood cell count and serum C-reactive protein levels, pyuria, and positive urine
      culture results were statistically higher in the older age group. The most common
      cause of acute epididymitis in children was idiopathic (96.1%). CONCLUSIONS: In
      our group of children with epididymitis, 73 cases out of 76 (96.1%) resulted in
      negative pyuria in urinalysis. In addition, the most common cause of epididymitis
      was idiopathic. Because most urinalyses do not show pyuria, we believe that
      routine antibiotics may be not required in pediatric patients with epididymitis.
      If urinalysis shows pyuria with or without positive urine culture, antibiotics
      should be considered.

PMID- 23550230
TI  - Cardiac troponin T levels of umbilical cord in neonates with abnormal fetal heart
      rate.
AB  - OBJECTIVE: Most neonatal encephalopathic disorders appear to be caused by
      perinatal events. Persistent myocardial ischemia leads to cellular necrosis and
      release of troponin from cardiac muscles. Fetal distress during labor may be
      detected by monitoring the fetal heart rate. However little is known about the
      relationship, if any, that exists between fetal heart rate abnormalities and the
      fetal cardiac musculature and its function. The aim of this study was to
      investigate the relationship, if any, of umbilical cord serum levels of cardiac
      troponin T with fetal bradycardia or late deceleration. METHODS: In this cross
      sectional study, troponin T level in umbilical cord blood of 80 neonates are
      measured. There were 23 versus 57 fetuses with and without late deceleration or
      bradycardia. FINDINGS: Level of cardiac troponin T in umbilical blood of neonates
      with fetal bradycardia or late deceleration was elevated in comparison to
      neonates without bradycardia or late deceleration. There was no relation between
      umbilical troponin T level and mode of delivery. CONCLUSION: Infants with fetal
      bradycardia or late deceleration during labor had significantly higher cord
      cardiac troponin T levels. If troponin level is normal, the probability of
      hypoxia will be very low.

PMID- 23550229
TI  - Kisspeptins and RFRP-3 Act in Concert to Synchronize Rodent Reproduction with
      Seasons.
AB  - Seasonal mammals use the photoperiodic variation in the nocturnal production of
      the pineal hormone melatonin to synchronize their reproductive activity with
      seasons. In rodents, the (SD) short day profile of melatonin secretion has long
      been proven to inhibit reproductive activity. Lately, we demonstrated that
      melatonin regulates the expression of the hypothalamic peptides kisspeptins (Kp)
      and RFamide-related peptide-3 (RFRP-3), recently discovered as potent regulators
      of gonadotropin-releasing hormone (GnRH) neuron activity. In the male Syrian
      hamster, Kp expression in the arcuate nucleus is down-regulated by melatonin
      independently of the inhibitory feedback of testosterone. A central or peripheral
      administration of Kp induces an increase in pituitary gonadotropins and gonadal
      hormone secretion, but most importantly a chronic infusion of the peptide
      reactivates the photo-inhibited reproductive axis of Syrian hamsters kept in SD
      conditions. RFRP-3 expression in the dorsomedial hypothalamus is also strongly
      inhibited by melatonin in a SD photoperiod. Although RFRP-3 is usually considered
      as an inhibitory component of the gonadotropic axis, a central acute
      administration of RFRP-3 in the male Syrian hamster induces a marked increase in
      gonadotropin secretion and testosterone production. Furthermore, a chronic
      central infusion of RFRP-3 in SD-adapted hamsters reactivates the reproductive
      axis, in the same manner as Kp. Both Kp and RFRP-3 neurons project onto GnRH
      neurons and both neuropeptides regulate GnRH neuron activity. In addition,
      central RFRP-3 infusion was associated with a significant increase in arcuate Kp
      expression. However, the actual sites of action of both peptides in the Syrian
      hamster brain are still unknown. Altogether our findings indicate that Kp and
      RFRP neurons are pivotal relays for the seasonal regulation of reproduction, and
      also suggest that RFRP neurons might be the primary target of the melatoninergic
      message.

PMID- 23550231
TI  - Molecular mechanism of the inhibition effect of Lipoxin A4 on corneal dissolving
      pathology process.
AB  - AIM: Excessive dissolve of corneal tissue induced by MMPs which were activated by
      cytokins and chemokines will lead to corneal ulcer. The molecular mechanism of
      Lipoxin A4 (LXA4) on corneal collagen degradation in three dimensions was
      investigated. METHODS: Rabbit corneal fibroblasts were harvested and suspended in
      serum-free MEM. Type I collagen, DMEM, collagen reconstitution buffer and corneal
      fibroblast suspension were mixed on ice. The resultant mixture solidified in an
      incubator, after which test reagents and plasminogen was overlaid and the
      cultures were returned to the incubator. The supernatants from collagen gel
      incubations were collected and the amount of hydroxyproline in the hydrolysate
      was measured. Immunoblot analysis of MMP-1, -3 and TMMP-1,-2 was performed. MMP
      2,-9 was detected by the method of Gelatin zymography. Cytotoxicity assay was
      measured. RESULTS: LXA4 inhibited corneal collagen degradation in a dose and time
      manner. LXA4 inhibited the IL-1beta induced increases in the pro-MMP-1, -2, -3, 
      9 and active MMP-1, -2, -3, -9 in a concentration dependent manner. LXA4 could
      also inhibit the IL-1beta induced increases in TIMP-1, -2. CONCLUSION: As a
      potent anti-inflammation reagent, LXA4 can inhibit corneal collagen degradation
      induced by IL-1beta in corneal fibroblasts thus inhibiting corneal dissolving
      pathology process.

PMID- 23550232
TI  - Acrylonitrile has Distinct Hormetic Effects on Acetyl-Cholinesterase Activity in
      Mouse Brain and Blood that are Modulated by Ethanol.
AB  - Acrylonitrile(AN) is a neurotoxin both in animals and humans, but its effects on
      acetylcholinesterase (AChE) activity remain controversial. This study aimed to
      determine the dose-response effects of AN on AChE activity and the modulatory
      role of ethanol pre-treatment. A total of 144 Kunming mice were randomly divided
      into 18 groups: nine groups received 5% ethanol in their drinking water, and the
      remaining nine groups received regular tap water. One week later, both the
      ethanol and tap water only groups were given an intraperitoneal injection of AN
      at the following doses: 0 (control), 0.156, 0.3125, 0.625, 1.25, 2.5, 5, 10 or 20
      mg AN/kg body weight. AChE activity was determined on whole blood and brain 24 h
      later. Blood AChE activity was higher in AN-injected mice than in controls at all
      doses. AChE activity in blood increased in a dose-dependent manner, peaking at
      0.156 mg/kg, after which a gradual decrease ensued, displaying a beta-typed dose
      response relationship. In contrast, brain AChE activity, following a single AN
      injection, was consistently lower than in control mice, and continued to fall up
      to a dose of 0.313 mg/kg, and thereafter increased gradually with higher doses.
      Mice receiving a 20 mg/kg dose of AN exhibited AChE brain activity
      indistinguishable from that of control mice, demonstrating a typical U-typed dose
      response relationship. The activity of AChE in the blood and brain of the AN +
      ethanol-treated groups displayed a shift to the right, and the magnitude of the
      decrease in AChE activity induced by AN was attenuated relative to the AN-only
      group. These results suggest that AN affects AChE activity in both mouse blood
      and brain in a hormetic manner. Pretreatment with ethanol modifies the effect of
      AN on AChE, indicating that parent AN has a more prominent role than its
      metabolites in modulating enzyme activity.

PMID- 23550233
TI  - Laparoscopic repair of large bladder herniation presenting as an inguinal hernia.
AB  - The bladder is involved in 1% to 3% of all hernia cases. We report a case of a
      large paraperitoneal bladder hernia (BH) in a 59-year-old man who had a palpable
      scrotal mass. Several techniques and approaches have been described for managing
      BHs. We performed a laparoscopic partial cystectomy and herniorrhaphy. This is
      the first case report on the repair of a large BH by use of a laparoscopic
      technique in Korea.

PMID- 23550234
TI  - Achieving Presence through Evoked Reality.
AB  - The sense of "Presence" (evolving from "telepresence") has always been associated
      with virtual reality research and is still an exceptionally mystifying
      constituent. Now the study of presence clearly spans over various disciplines
      associated with cognition. This paper attempts to put forth a concept that argues
      that it's an experience of an "Evoked Reality (ER)" (illusion of reality) that
      triggers an "Evoked Presence (EP)" (sense of presence) in our minds. A Three Pole
      Reality Model is proposed to explain this phenomenon. The poles range from Dream
      Reality to Simulated Reality with Primary (Physical) Reality at the center. To
      demonstrate the relationship between ER and EP, a Reality-Presence Map is
      developed. We believe that this concept of ER and the proposed model may have
      significant applications in the study of presence, and in exploring the
      possibilities of not just virtual reality but also what we call "reality."

PMID- 23550235
TI  - A Chinese Girl with Bartter Syndrome Type III due to a Novel Mutation and/or
      Single Nucleotide Polymorphisms (SNPs) in CLCNKB Gene.
AB  - BACKGROUND: Bartter's syndrome is a heterogeneous disorder characterized by
      deficient renal reabsorption of sodium and chloride, and hypokalemic metabolic
      alkalosis with hyper-reninemia and hyperaldosteronemia. Bartter syndrome type III
      (BS type III), due to mutations in the CLCNKB gene, is highly variable. The aim
      of our study was to describe the clinical presentation in a Chinese girl with BS
      type III and to explore mutations or SNPs of CLCNKB gene in her family. CASE
      PRESENTATION: The clinic data of the patient was collected. Mutations or SNPs
      were investigated by sequencing of the exon of CLCNKB gene. The clinic analysis
      confirmed the diagnosis of BS type III. The coexistence of 13 reported SNPs and
      11 novel SNPs of CLCNKB gene were found in the patient and her parent. a novel
      heterozygous C to G transition at nucleotide 2471 in exon 20 of CLCNKB gene
      harbored uniquely by the patient were revealed. CONCLUSION: A novel heterozygous
      C to G mutation at nucleotide 2471 of CLCNKB gene and some new SNPs were
      identified in a Chinese girl with BS type III having persistent hypokalemia. The
      novel mutation and SNPs make the genetic background of the patient more
      complicated.

PMID- 23550236
TI  - Work related encounters in general practice.
AB  - General practitioner participants in the BEACH (Bettering the Evaluation and Care
      of Health) program were asked to indicate which problems managed at the encounter
      were considered to be work related. From April 2007 to March 2012, at least one
      work related problem was managed at 2.7% of all encounters (11 429 encounters). A
      total of 16 045 problems were managed at these encounters, of which 11 911
      (74.2%) were work related. Three-quarters (75.7%) of recorded work related
      encounters were claimable through workers' compensation.

PMID- 23550237
TI  - Presenteeism--implications and health risks.
AB  - BACKGROUND: Presenteeism - or working while ill - is commonly seen as just an
      economic indicator of disease burden. Emerging evidence suggests it may best be
      conceptualised as a behaviour that has implications for the person and their
      employer, and one that can be clinically managed. OBJECTIVE: This article
      presents an overview of the phenomenon of presenteeism in the workforce and its
      clinical implications. It focuses on evidence relevant to the management of day
      to-day, short term decisions on whether an individual should go into work while
      sick or take a day or more of work absence. This discussion is separate to the
      management of compensation and return to work issues. DISCUSSION: Certain
      patients will be at risk of presenteeism, even when absence may be clinically
      advisable, due to personal or job characteristics. Presenteeism behaviour has
      potential positive and negative consequences for the patient's own health, their
      job performance and tenure and their workplace, and these should be weighed up
      when helping patients to manage their work responsibilities.

PMID- 23550238
TI  - Tendon injuries--practice tips for GPs.
AB  - BACKGROUND: Tendon injuries are common, generally degenerative in nature, and can
      cause significant morbidity if not appropriately managed. OBJECTIVE: This article
      outlines some key principles about tendon injuries with a particular focus on
      diagnosis and management. DISCUSSION: Diagnosis is made primarily on history and
      examination with imaging prescribed for unusual or recalcitrant cases.
      Examination elicits local tendon tenderness, pain with passive stretch, and pain
      with active contraction or specific provocative tests. Treatment involves pain
      control and musculotendinous rehabilitation. Pain control may include the
      application of ice, bracing and medications. Exercise rehabilitation is the
      mainstay of treatment for chronic tendon injuries and must include stretch and
      strengthening exercises. Generally, strengthening exercises for tendon injuries
      are eccentric in nature and should be performed relatively pain-free. Injectable
      modalities may be used as an adjunct to decrease pain and facilitate exercise
      rehabilitation, but should not be used in isolation.

PMID- 23550239
TI  - Returning to work after an injury.
AB  - BACKGROUND: Workplace injuries are common, cause significant morbidity for
      workers and have considerable economic impact. General practitioners can play an
      important role in facilitating early return to work, improving outcomes for all
      parties. OBJECTIVE: This article provides guiding principles for the initial
      assessment and early treatment phase of injury with a primary focus on the
      rehabilitation and return to work process. DISCUSSION: A case management approach
      to assist injured workers return to work that involves collaboration between the
      injured worker, medical and rehabilitation providers, the employer and work
      insurers, achieves better outcomes. Efficient rehabilitation involves good
      initial assessment, effective early treatment, early mobilisation and good
      communication between all parties. General practitioners have an important role
      to play in facilitating this process.

PMID- 23550240
TI  - Workplace bullying--what's it got to do with general practice?
AB  - BACKGROUND: Workplace bullying is repeated systematic, interpersonal abusive
      behaviours that negatively affect the targeted individual and the organisation in
      which they work. It is generally the result of actual or perceived power
      imbalances between perpetrator and victim, and includes behaviours that
      intimidate, offend, degrade or humiliate a worker. It is illegal, and bullied
      employees can take legal action against their employers for a breach of implied
      duty of trust and confidence. Despite this, workplace bullying occurs in many
      Australian workplaces, including Australian general practices. OBJECTIVE: This
      article explores the issue of workplace bullying with particular reference to
      bullying within general practice and provides a framework for managing these
      situations. DISCUSSION: All general practices need organisation-wide anti
      bullying policies that are endorsed by senior management, clearly define
      workplace bullying, and provide a safe procedure for reporting bullying
      behaviours. General practitioners should investigate whether workplace issues are
      a potential contributor to patients who present with depression and/or anxiety
      and assess the mental health of patients who do disclose that they are victims of
      workplace bullying, Importantly, the GP should reassure their patient that
      bullying is unacceptable and illegal, and that everyone has the right to a safe
      workplace free from violence, harassment and bullying. The time has come for all
      workplaces to acknowledge that workplace bullying is unacceptable and
      intolerable.

PMID- 23550241
TI  - Chronic fatigue syndrome--a patient centred approach to management.
AB  - BACKGROUND: Chronic fatigue syndrome (myalgic encephalomyelitis) is a diagnosis
      that can attract feelings of stigma in the patient due to the lack of a definite
      diagnostic biomarker. To ensure that the patient firstly understands the
      diagnosis, and subsequently is comfortable with the treatment suggested, a
      patient centred approach is advised within the consultation. OBJECTIVE: This
      article presents a hypothetical case and uses this to give guidance on methods
      for negotiating the diagnosis and treatment of chronic fatigue syndrome.
      DISCUSSION: It is important to reassure the patient that negative investigation
      results and the suggestion of treatment options that are also used for depressive
      illness (eg. antidepressants and cognitive behavioural therapy), does not mean
      that their illness experience is fabricated or that they are being treated for
      depression. Once red flag features are ruled out and any exclusory illnesses
      identified, a multidisciplinary pragmatic rehabilitation program can be
      implemented. This includes strategies for increasing social support, liaising
      with employers and graded return to activities in a 'What matters to you?'
      approach.

PMID- 23550242
TI  - Quantitative serum immunoglobulin tests.
AB  - What is the test? Immunoglobulins are protein molecules. They contain antibody
      activity and are produced by the terminal cells of B-cell differentiation known
      as 'plasma cells'. There are five classes of immunoglobulin (Ig): IgG, IgM, IgA,
      IgD and IgE. In normal serum, about 80% is IgG, 15% is IgA, 5% is IgM, 0.2% is
      IgD and a trace is IgE. Quantitative serum immunoglobulin tests are used to
      detect abnormal levels of the three major classes (IgG, IgA and IgM). Testing is
      used to help diagnose various conditions and diseases that affect the levels of
      one or more of these immunoglobulin classes. Some conditions cause excess levels,
      some cause deficiencies, and others cause a combination of increased and
      decreased levels. IgD and IgE will not be discussed in this article.

PMID- 23550243
TI  - Bibliotherapy for depression.
AB  - Bibliotherapy can be used to treat mild to moderate depression or subthreshold
      depressive symptoms, as a sole or supplementary therapy. Bibliotherapy is a form
      of guided self-help. The patient works through a structured book, independently
      from the doctor. The role of the doctor is to support and motivate the patient as
      they continue through the book and to help clarify any questions or concerns the
      patient may have. Relevant books can be purchased or often borrowed from a
      library, with limited cost and good accessibility from a patient perspective.
      Patients need to have a reading age above 12 years and have a positive attitude
      toward self-help. Bibliotherapy has NHMRC Level 1 evidence of efficacy and no
      serious adverse effects have been reported. This article forms part of a series
      on non-drug treatments, which summarise the indications, considerations and the
      evidence, and where clinicians and patients can find further information.

PMID- 23550244
TI  - Digital eye drop instillation--a novel method.
AB  - BACKGROUND: Local drug treatment in ophthalmology by the use of eye drops has
      meant that potent drugs can be used, thereby minimising systemic side effects.
      While seemingly a simple task, insertion of eye drops can be problematic for
      certain patients and in particular circumstances. OBJECTIVE: To describe a novel
      method for the administration of eye drops, which overcomes the main problems of
      conventional eye drop administration. DISCUSSION: Our pragmatic method of eye
      drop application provides a way of improving compliance and reducing ocular
      surface injury. Our experience to date is that the technique is at least as safe
      as that used for insertion of contact lenses from an infection risk perspective.

PMID- 23550245
TI  - Extrapulmonary tuberculosis--three cases in the spine.
AB  - BACKGROUND: Tuberculosis is the second most common fatal infectious disease in
      the world. However, it is an uncommon presentation in the Australian primary care
      setting. OBJECTIVE: This article describes three cases of extrapulmonary
      tuberculosis (EPTB) of the spine that presented to Australian general practices;
      discusses features that may lead the general practitioner to consider a diagnosis
      of EPTB; and considers the investigation options for osseous EPTB. DISCUSSION:
      All three cases presented complaining of cervical, thoracic or lumbar pain of
      some months duration. All three patients were migrants from India who were HIV
      negative and who had resided in Australia for a period of 3-8 years. Two of the
      patients had potentially unstable conditions of the spine, meaning there was a
      risk of permanent neurological damage. All three patients responded to anti
      tuberculosis multidrug therapy. These cases highlight the possibility of EPTB as
      a differential diagnosis in the presentation of back pain in selected
      populations.

PMID- 23550246
TI  - Complex type 2 diabetes mellitus--management challenges and pitfalls.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus frequently have comorbidities
      that complicate the management of their disease. Many of these patients are
      prescribed multiple medications to manage hyperglycaemia, hypertension and other
      comorbidities. Clinicians who manage these patients must deal with the challenge
      of adjusting multiple medications in the face of renal failure and cardiovascular
      disease as the disease progresses, as well as tailoring therapy to help patients
      overcome intolerances and adverse effects. OBJECTIVE: This article explores some
      of the issues in managing the complex patient, including non-adherence and the
      challenges associated with achieving glycaemic control in patients with
      cardiovascular disease and renal impairment. DISCUSSION: Generalists,
      specifically general practitioners, are well suited to address the complexities
      of the management of type 2 diabetes mellitus patients. They need to be able to
      assess the risks and benefits of each treatment decision in light of the
      patient's glycaemic control, cardiovascular status, renal function and
      motivation.

PMID- 23550247
TI  - Subungual nodule of the great toe.
AB  - An otherwise healthy male, 17 years of age, presented with a 2 year history of an
      enlarging lump under the right great toenail. There was no history of trauma.
      Examination revealed an exophytic, non-tender, fixed, firm flesh-coloured
      subungal nodule on the dorsal aspect of the right great toe. The lesion was about
      10 mm in diameter and was associated with nail plate deformity and onycholysis.

PMID- 23550248
TI  - Prostatitis--diagnosis and treatment.
AB  - Prostatitis is a spectrum of disorders that impacts a significant number of men.
      Acute bacterial prostatitis may be a life-threatening event requiring prompt
      recognition and treatment with antibiotic therapy. Chronic bacterial prostatitis
      has a more indolent course and also requires antibiotic therapy for resolution.
      Chronic prostatitis/chronic pelvic pain syndrome is the most common manifestation
      of prostatitis and may be the most difficult to treat. Asymptomatic inflammatory
      prostatitis is an incidental finding of unclear significance. Understanding the
      diagnostic and management strategies for each of these entities is critical for
      general practitioners in caring for their male patients.

PMID- 23550249
TI  - Training in critical thinking and research--an audit of delivery by regional
      training providers in Australia.
AB  - BACKGROUND: Critical thinking and research are important career skills for
      general practitioners. Vocational training in this aspect of The Royal Australian
      College of General Practitioners (RACGP) curriculum varies between regional
      training providers (RTPs). METHODS: A cross-sectional audit examining the
      delivery of the 'critical thinking and research' component of the RACGP
      curriculum at the RTP level, and documenting factors related to capacity and
      competence to deliver this training. RESULTS: Heterogeneity across RTPs was seen
      in the mode and intensity of education activities pertaining to critical thinking
      and research and in surrogate measures of capacity and competence to deliver this
      training. DISCUSSION: This study suggests that the training general practice
      registrars receive in research and critical thinking may vary according to which
      RTP delivers the training. This is of concern as it means that the knowledge and
      skills base of the next generation of GPs in this area is likely to be similarly
      variable, impacting on their ability to practise high quality, evidence based
      medicine. Critical thinking and research should be recognised as a priority area
      in vocational training across all RTPs.

PMID- 23550250
TI  - Chronic hepatitis B--care delivery and patient knowledge in the Torres Strait
      region of Australia.
AB  - BACKGROUND: Chronic hepatitis B (CHB) disproportionately affects Indigenous
      Australians. This article reports the findings of two studies in the Torres
      Strait and Northern Peninsula area (T&NPA) of Queensland in Australia. The aim of
      the first study was to assess CHB care delivery, the second assessed CHB patient
      knowledge about the condition. METHODS: A pathology database search (1997-2009)
      identified a cohort of potential CHB patients in T&NPA. A file audit assessed
      care delivery for a random sample of 83 CHB patients. A survey assessed knowledge
      of 42 CHB patients. RESULTS: A total of 365 hepatitis B positive patients were
      identified. There are gaps in patient review, monitoring, follow up and
      specialist referral. Patients had limited knowledge about CHB and measures to
      reduce its health impact. DISCUSSION: Chronic hepatitis B affects a substantial
      number of Indigenous adults in the T&NPA. There is limited adherence to clinical
      guidelines. Improved uptake of clinical guidelines adapted for remote areas,
      incorporation of CHB into systematic chronic disease care, and culturally
      appropriate patient education resources and programs are needed.

PMID- 23550251
TI  - Home blood pressure monitoring--a trial on the effect of a structured education
      program.
AB  - BACKGROUND: This study aimed to assess whether a structured home blood pressure
      monitoring (HBPM) education program can improve blood pressure control in
      patients. METHODS: A cluster randomised controlled trial in which half of 240
      patients in the intervention group received an education program focused on using
      HBPM machines at home, while the other half had the usual care. The primary
      endpoints were mean systolic blood pressure and diastolic blood pressure.
      RESULTS: Systolic blood pressure dropped 1.88 mmHg (p=0.372) and diastolic blood
      pressure significantly dropped 3.84 mmHg (p=0.004) in intervention group at 3
      months. At 6 months, systolic blood pressure and diastolic blood pressure were
      still on a decreasing trend, but there was no significant difference in blood
      pressure changes between the two groups. DISCUSSION: The structured HBPM
      education program has the potential to improve patient blood pressure control at
      short term, but such effect appears tailing off at medium terms. Additional
      components may be needed to maximise and sustain the benefit of HBPM.

PMID- 23550252
TI  - Managing same day appointments--a qualitative study in Australian general
      practice.
AB  - BACKGROUND: General practices are required to have flexible systems to
      accommodate urgent appointments. Not all patients requesting a same day
      appointment receive one. There is scant research detailing how requests for same
      day appointments are managed. Our study examined this issue from the perspective
      of practice staff. METHODS: Twenty practice staff (receptionists, practice
      managers, general practitioners, practice nurse) from 10 general practices
      participated in semistructured interviews, which were audiorecorded, transcribed
      and analysed thematically. RESULTS: All but three practices set aside
      appointments for patients requesting a same day appointment. Themes included
      contradictions between policy and practice and the role of experience in
      determining urgency. Five types of urgent needs for same day appointments were
      identified: medical, administrative, therapeutic, logistic and emotional.
      DISCUSSION: Practice policies must make clear roles and responsibilities for all
      staff managing patient appointments. Aspects of clinic policies and practices
      could be reviewed to reduce medicolegal risk and additional workload caused by
      non-medically urgent needs.

PMID- 23550253
TI  - The duty of GPs to follow up patients.
AB  - A recent Supreme Court of Victoria judgement examined the legal obligations of a
      general practitioner to recall a patient who does not undergo a test that has
      been recommended by the GP or to return for a consultation, despite being asked
      to do so.

PMID- 23550254
TI  - The pre-employment medical--ethical dilemmas for GPs.
AB  - BACKGROUND: In many workplaces, employment is conditional on a successful pre
      employment medical examination. This examination is usually conducted by a
      general practitioner on the employers' panel of approved clinics or by an in
      house company doctor. OBJECTIVE: This article uses a case study to illustrate
      some of the ethical dilemmas that may be faced by GPs in the course of performing
      a pre-employment medical examination. DISCUSSION: Ethical issues discussed in
      this article include: Is it ethical for employers (based on physicians' reports)
      to select workers based on 'absence of illness' rather than 'fitness for work'?
      Should physicians divulge the illness of potential workers to third parties? What
      are the boundaries of a clinician's duty of care in the pre-employment medical
      examination setting?

PMID- 23550255
TI  - Anti-TNF agents for the treatment of active non-radiographic axial
      spondyloarthritis.

PMID- 23550256
TI  - Italian Society of Rheumatology recommendations for the management of gout.
AB  - OBJECTIVE: Gout is the most common arthritis in adults. Despite the availability
      of valid therapeutic options, the management of patients with gout is still
      suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to
      national contest and disseminate the 2006 EULAR recommendations for the
      management of gout. METHODS: The multidisciplinary group of experts included
      rheumatologists, general practitioners, internists, geriatricians, nephrologists,
      cardiologists and evidence-based medicine experts. To maintain consistency with
      EULAR recommendations, a similar methodology was utilized by the Italian group.
      The original propositions were translated in Italian and priority research
      queries were identified through a Delphi consensus approach. A systematic search
      was conducted for selected queries. Efficacy and safety data on drugs reported in
      RCTs were combined in a meta-analysis where feasible. The strength of
      recommendation was measured by utilising the EULAR ordinal and visual analogue
      scales. RESULTS: The original 12 propositions were translated and adapted to
      Italian context. Further evidences were collected about the role of diet in the
      non-pharmacological treatment of gout and the efficacy of oral corticosteroids
      and low-dose colchicine in the management of acute attacks. Statements concerning
      uricosuric treatments were withdrawn and replaced with a proposition focused on a
      new urate lowering agent, febuxostat. A research agenda was developed to identify
      topics still not adequately investigated concerning the management of gout.
      CONCLUSIONS: The SIR has developed updated recommendations for the management of
      gout adapted to the Italian healthcare system. Their implementation in clinical
      practice is expected to improve the management of patients with gout.

PMID- 23550257
TI  - Duration of treatment for osteoporosis.
AB  - Many treatments for postmenopausal osteoporosis with proven efficacy in lowering
      fracture risk had become available since many years now. In the last few years
      the issue about treatment duration has become a matter of importance. In this
      paper the pivotal trials for alendronate, risedronate, zoledronate and other anti
      reabsorptive drugs such as denosumab are revised with particular attention to the
      extension studies aimed to verify the effect of drug discontinuation. The results
      of the review highlight differences among the available drugs and the practical
      clinical consequences also in terms of cost-effectiveness.

PMID- 23550258
TI  - Giant cell arteritis associated with chronic active Epstein-Barr virus infection.
AB  - Giant cell arteritis is an inflammatory vasculopathy that preferentially affects
      medium-sized and large arteries. A viral cause has been suspected but not
      confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case
      of a 81-year-old female who suffered from chronic active Epstein-Barr virus
      infection and developed giant cell temporal arteritis.

PMID- 23550259
TI  - Papular-purpuric gloves and socks syndrome due to parvovirus B19: a report of two
      simultaneous cases in cohabitant families.
AB  - The so-called papular-purpuric gloves and socks syndrome (PPGSS) is a condition
      characterized by acute onset of intense erythema, edema and petechiae with a
      typical localization on the hands and feet, besides mucosal lesions of the oral
      cavity. The syndrome has a favorable and self-limited course, requiring only a
      symptomatic therapy. In the 50% of the cases described in literature (ninety
      cases in 22 years), is documented an acute infection caused by parvovirus B19 and
      in only two cases the onset of PPGSS is reported among different members of the
      same family. The aim of the work is to describe two cases of PPGSS arisen during
      a short time period in two family members affected by an acute parvovirus B19
      infection found by serum sampling. The peculiarity of the study was the
      infrequence of the syndrome and the rareness of the description of PPGSS in
      rheumatology. This syndrome is usually described in dermatology, but it is also
      interesting for the rheumatologist because it comes in differential diagnosis
      with various autoimmune diseases.

PMID- 23550260
TI  - Diffusion and applications of musculoskeletal ultrasound in Italian Rheumatology
      Units.
AB  - The Musculoskeletal Ultrasound Study Group of the Italian Society of Rheumatology
      (SIR) was founded during the 68th SIR Congress, on November 2011. The request of
      activation of this group was based on the increasing interest and the widespread
      diffusion of ultrasound in the scientific rheumatology community and on the solid
      experience of some Italian rheumatologists in the field. The aims of the Study
      Group are to stimulate the applications and use of ultrasound in the clinical
      practice at the level of the Italian rheumatology units and, in addition, to
      develop research projects at a national level...

PMID- 23550261
TI  - The role of the cytokines in the pathogenesis of pseudoexfoliation syndrome.
AB  - AIM: To examine the mechanism of the development of pseudoexfoliation (PSX)
      syndrome via both cytokine formation and endothelial vasorelaxing and growth
      factors that will provide us new therapeutic insights for the treatment. METHODS:
      This is a cross sectional study included two groups; Group 1: control patients
      with nuclear cataract (n=20, aged 51-80 years). Group 2: PSX patients with
      nuclear cataract (n=18, aged 50-90 years). Patients with other ophthalmic
      problems and systemic diseases were excluded. Vascular endothelial growth factor
      (VEGF), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) and nitrotyrosine
      levels were determined through serum samples by Enzyme-linked immunosorbent assay
      (ELISA) method. Nitrite-nitrate levels were measured with photometric endpoint
      determination. RESULTS: There were no significant differences between the groups
      in terms of age, VEGF, IL-1beta, nitrite-nitrate and nitrotyrosine. The
      significant results were the mean IL-6 levels that were higher in PSX group 2
      (37.68+/-29.52 pg/mL) compared to that in control group 1 (15.32+/-10.08 pg/mL)
      (P<0.001). CONCLUSION: Several interacting and extending biochemical pathways may
      lead to the promotion of VEGF and IL-6 expressions. IL-6 which is the only
      altered marker in our study may indirectly cause an increase of vascular
      permeability and neovascularization. We suggest inflammation as a factor that can
      be involved in etiopathogenesis of PSX.

PMID- 23550262
TI  - The late and persistent pathogenic effects of cadmium at very low levels on the
      kidney of rats.
AB  - Cadmium (Cd) is an important nephrotoxic pollutant. To examine late effects on
      the kidney of individuals previously exposed to chronic Cd at very low levels,
      male Wistar rats were given 20 nmol/kg i.p. injections of Cd every other day for
      4 weeks. At the 20(th), 28(th), 36(th), 44(th) and 52(nd) week of the study,
      renal metal accumulation, morphology and function were examined. Immunochemical
      staining was performed to detect renal 3-nitrotyrosine (3-NT) accumulation,
      metallothionein (MT) expression, cell proliferation and global DNA methylation.
      Results showed that renal Cd concentration and MT expression along with 3-NT
      accumulation were significantly higher in the Cd group than that in the control.
      Histopathologically renal tubule damage at the early stage and hyperplasia at the
      late stage were observed in the Cd group. Renal fibrosis in glomeruli was evident
      in the Cd group, particularly at the late stage of the study. Immunoreactivity of
      global DNA methylation was markedly diminished in the Cd group at both 20(th) and
      52(nd) weeks. These results suggest that previous exposure to chronic Cd at very
      low level induced persistent damaging effects on the kidney along with increases
      in cell proliferation and global DNA hypomethylation.

PMID- 23550263
TI  - Ileo-pelvic anastomosis and augmentation cystoplasty for treatment of encrusted
      pyelitis in a transplanted kidney.
AB  - Infection stones are more likely to form after urinary diversion as the result of
      urinary stasis. To prevent urinary stasis due to encrusted pyelitis in a
      transplanted kidney, we describe an alternative a surgical treatment: ileo-pelvic
      anastomosis. In our patient with a transplanted kidney, the ileal conduit had
      previously been anastomosed end-to-side owing to renal tuberculosis with an
      atrophied bladder; the transplanted ureter was anastomosed to the ileum in the
      left lower abdomen with an ileal conduit on the opposite side. Routine check-up
      revealed hydronephrosis with infected pyelitis and ureteritis in the transplanted
      kidney. We performed ileo-pelvic end-to-end anastomosis to prevent urinary stasis
      by lengthening the ileal conduit and performed augmentation cystoplasty to
      support the atrophied bladder following tuberculosis. We suggest that this
      approach may be useful in similar cases.

PMID- 23550264
TI  - Attempting measurement of psychological attributes.
AB  - Measures of psychological attributes abound in the social sciences as much as
      measures of physical properties do in the physical sciences. However, there are
      crucial differences between the scientific underpinning of measurement. While
      measurement in the physical sciences is supported by empirical evidence that
      demonstrates the quantitative nature of the property assessed, measurement in the
      social sciences is, in large part, made possible only by a vague, discretionary
      definition of measurement that places hardly any restrictions on empirical data.
      Traditional psychometric analyses fail to address the requirements of measurement
      as defined more rigorously in the physical sciences. The construct definitions do
      not allow for testable predictions; and content validity becomes a matter of
      highly subjective judgment. In order to improve measurement of psychological
      attributes, it is suggested to, first, readopt the definition of measurement in
      the physical sciences; second, to devise an elaborate theory of the construct to
      be measured that includes the hypothesis of a quantitative attribute; and third,
      to test the data for the structure implied by the hypothesis of quantity as well
      as predictions derived from the theory of the construct.

PMID- 23550265
TI  - Whole lung lavage of nine children with pulmonary alveolar proteinosis:
      experience in a tertiary lung center.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease in children,
      characterized by intra-alveolar accumulation of large amounts of surfactant
      proteins, which severely reduce gas exchange. Whole lung lavage (WLL) is the
      preferred technique for the treatment of severe PAP. CASE PRESENTATION: This
      report presents nine pediatric cases with advanced PAP who underwent WLL under
      general anesthesia during a 9 year period. One patient was treated with multiple
      unilateral WLL without employing cardiopulmonary bypass (CPB) and eight cases
      were treated by simultaneous lavage of both lungs using partial CPB. CONCLUSION:
      Our experience suggested that partial CPB was useful to support oxygenation
      during WLL in small children with severe PAP in whom lung separation and
      selective lavaging of each lung were impracticable.

PMID- 23550266
TI  - Expressions of type I collagen, alpha2 integrin and beta1 integrin in sclera of
      guinea pig with defocus myopia and inhibitory effects of bFGF on the formation of
      myopia.
AB  - AIM: To investigate the expressions of type I collagen, alpha2 integrin and beta1
      integrin in the posterior sclera of guinea pigs with defocus myopia and whether
      basic fibroblast growth factor (bFGF) injection inhibits the formation and
      development of myopia by upregulating the expression of type I collagen, alpha2
      integrin and beta1 integrin. METHODS: After 14 days of treatment, the refractive
      state and axial length were measured and the levels of type I collagen, alpha2
      integrin and beta1 integrin were assayed in the posterior sclerae of groups of
      guinea pigs that wore a monocular -7D polymethylmethacrylate (PMMA) lens or had 
      7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution
      (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no
      treatment served as normal group. RESULTS: The results showed that 14 days of
      monocular defocus increased axial eye length and refraction, while bFGF delivery
      inhibited them markedly. Further, it was also found that the monocular -7D lens
      could decrease the levels of type I collagen, alpha2 integrin and beta1 integrin
      expressions, while, unlike PBS, bFGF increased them significantly in comparison
      to contralateral control eyes and normal eyes. CONCLUSION: bFGF can prevent the
      formation and development of defocus myopia by upregulating the expressions of
      type I collagen, alpha2 integrin and beta1 integrin. Taken together, our results
      demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea
      pigs.

PMID- 23550267
TI  - Chlamydia and male lower urinary tract diseases.
AB  - Of the chlamydia species that can cause infections in humans, C. trachomatis is
      responsible for lower urinary tract diseases in men and women. C. trachomatis
      infections are prevalent worldwide, but current research is focused on females,
      with the burden of disease and infertility sequelae considered to be a
      predominantly female problem. However, a role for this pathogen in the
      development of male urethritis, epididymitis, and orchitis is widely accepted.
      Also, it can cause complications such as chronic prostatitis and infertility.
      This review summarizes C. trachomatis infection in the male genitourinary tract,
      including urethritis, epididymitis, orchitis, and its complications, and
      addresses the microbiology, epidemiology, screening, clinical manifestations,
      diagnosis, and treatment.

PMID- 23550268
TI  - Alternative medicine techniques have non-linear effects on radiation response and
      can alter the expression of radiation induced bystander effects.
AB  - Many so-called "alternative medicine" techniques such as Reiki and acupuncture
      produce very good outcomes for intractable pain and other chronic illnesses but
      the efficacy is often dismissed as being psychosomatic. However a plausible
      mechanism does exist i.e. that the treatments alter the electromagnetic fields in
      living organisms and thereby prevent or reduce activity of neurons which lead to
      the pain. Low doses of ionising radiation have similar effects on electromagnetic
      fields and are known to induce signaling cascades in tissues due to ion
      gradients. To test this hypothesis cell cultures were exposed to Reiki - like and
      to acupuncture - like treatments, both performed by qualified practitioners. The
      cells were exposed either before or after the treatment to x-rays and were
      monitored for production of direct damage or bystander signals. The data suggest
      that the alternative techniques altered the response of cells to direct
      irradiation and altered bystander signal mechanisms. We conclude that alternative
      medicine techniques involving electromagnetic perturbations may modify the
      response of cells to ionizing radiation. In addition to the obvious implications
      for mechanistic studies of low dose effects, this could provide a novel target to
      exploit in radiation protection and in optimizing therapeutic gain during
      radiotherapy.

PMID- 23550270
TI  - Cutaneous sarcoid-like granulomas in a child known with nijmegen breakage
      syndrome.
AB  - BACKGROUND: Nijmegen Breakage Syndrome(NBS) is a rare autosomal recessive
      disorder with specific clinical features, characteristic chromosomal breakage and
      combined imunodeficiency. Patients with this condition also associate growth
      retardation with microcephaly, predisposition to malignancy and specific skin
      manifestations. CASE PRESENTATION: Here we report a 3-year old girl known with
      NBS associated with cutaneous sarcoid-like lesions. She presented with one year
      history of squamous lesions on the face and upper and lower limbs. The lesions
      were biopsied and histopatological examination revealed nonnecrotizing epitheloid
      granulomas and raised the suspicion of a sarcoid-like entity. CONCLUSION: The
      interest of this case will serve to better understand clinical manifestations in
      a rare genetic entity. Close follow-up is advised as cutaneous granulomas may be
      the first manifestation of systemic granulomas.

PMID- 23550269
TI  - Differential auditory-oculomotor interactions in patients with right vs. left
      sided subjective tinnitus: a saccade study.
AB  - Subjective tinnitus (ST) is a frequent but poorly understood medical condition.
      Recent studies demonstrated abnormalities in several types of eye movements
      (smooth pursuit, optokinetic nystagmus, fixation, and vergence) in ST patients.
      The present study investigates horizontal and vertical saccades in patients with
      tinnitus lateralized predominantly to the left or to the right side. Compared to
      left sided ST, tinnitus perceived on the right side impaired almost all the
      parameters of saccades (latency, amplitude, velocity, etc.) and noticeably the
      upward saccades. Relative to controls, saccades from both groups were more
      dysmetric and were characterized by increased saccade disconjugacy (i.e., poor
      binocular coordination). Although the precise mechanisms linking ST and saccadic
      control remain unexplained, these data suggest that ST can lead to detrimental
      auditory, visuomotor, and perhaps vestibular interactions.

PMID- 23550271
TI  - Impact of Lycium Barbarum Polysaccharide and Danshensu on vascular endothelial
      growth factor in the process of retinal neovascularization of rabbit.
AB  - AIM: To discuss the impact of Lycium Barbarum Polysaccharide (LBP) and Danshensu
      purified from Traditional Chinese Medicine (TCM) on vascular endothelial growth
      factor (VEGF) of rabbits with retinal neovascularization. METHODS: Forty rabbits
      were divided into normal control group, model control group, LBP group and
      Danshensu group. Animals in the normal control group were fed in the normal
      oxygen environment. Animals in the other three groups were put into the
      environment with 70% oxygen for 5 days in order to build the model of oxygen
      induced vascular proliferation retinopathy. And then different TCM extract was
      injected into the abdominal cavities of these annimals. After 7 days, the VEGF
      content of in the serum of rabbit was measured by double antibody sandwich
      method. RESULTS: DATA ANALYSIS INDICATED THAT VEGF CONTENT WAS AS FOLLOWS:
      Danshensu group was lower than model control group (12.92+/-3.84ng/L vs 19.32+/
      4.15ng/L, P<0.05); LBP group and normal control group were lower than model
      control group (12.92+/-3.84ng/L, 9.26+/-1.61ng/L vs 19.32+/-4.15ng/L, P<0.01);
      total blood viscosity, plasma viscosity, cholesterol content, fibrinogen content
      and triacylglycerol content after peritoneal injection of LBP and Danshensu were
      obviously lower than before injection. CONCLUSION: TCM extract-LBP and Danshensu
      can prominently reduce the content of VEGF in the process of vascular
      proliferative retinopathy of rabbit; can prevent the occurrence of retinal
      microvascular disease by improving partial oxygen-deficient environment or
      affecting all kinds of new growth factor.

PMID- 23550272
TI  - Simplified zero ischemia in robot assisted partial nephrectomy: initial yonsei
      experience.
AB  - PURPOSE: To evaluate the safety and feasibility of a simplified zero ischemia
      technique using kidney donor computed tomographic (CT) angiography and
      conventional laparoscopic bulldog clamps. MATERIALS AND METHODS: We conducted a
      review of seven robot-assisted partial nephrectomies (RAPNs) performed by a
      single surgeon from January 2012 to May 2012. Using a simplified protocol of 3
      dimentional reconstruction, tertiary arterial branches supplying the tumor were
      selectively clamped prior to resection. We used conventional laparoscopic bulldog
      clamps instead of microsurgical vessel clamps. The patients' demographic
      information, perioperative outcomes, pathologic outcomes and pre- and
      postoperative renal functions up to 3 months follow-up were analyzed. RESULTS:
      RAPN were successfully performed for seven complex renal hilar tumors. There were
      no significant differences in the total operation time, estimated blood loss or
      postoperative outcomes compared with published literature on standard RAPN.
      Negative surgical margins were reported in all cases. CONCLUSIONS: We presented a
      simplified-zero ischemia technique using kidney Donor CT angiography and
      conventional laparoscopic bulldog clamps. We have also demonstrated its safety
      and feasibility in patients with complex renal hilar tumors. This modified
      technique can be easily adopted by most surgeons who are currently performing
      RAPN.

PMID- 23550273
TI  - Modulation of untruthful responses with non-invasive brain stimulation.
AB  - Deceptive abilities have long been studied in relation to personality traits.
      More recently, studies explored the neural substrates associated with deceptive
      skills suggesting a critical role of the prefrontal cortex. Here we investigated
      whether non-invasive brain stimulation over the dorsolateral prefrontal cortex
      (DLPFC) could modulate generation of untruthful responses about subject's
      personal life across contexts (i.e., deceiving on guilt-free questions on daily
      activities; generating previously memorized lies about past experience; and
      producing spontaneous lies about past experience), as well as across modality
      responses (verbal and motor responses). Results reveal that real, but not sham,
      transcranial direct current stimulation (tDCS) over the DLPFC can reduce response
      latency for untruthful over truthful answers across contexts and modality
      responses. Also, contexts of lies seem to incur a different hemispheric
      laterality. These findings add up to previous studies demonstrating that it is
      possible to modulate some processes involved in generation of untruthful answers
      by applying non-invasive brain stimulation over the DLPFC and extend these
      findings by showing a differential hemispheric contribution of DLPFCs according
      to contexts.

PMID- 23550275
TI  - Decreased expression of the mitochondrial metabolic enzyme  aconitase (ACO2) is
      associated with poor prognosis in gastric  cancer.
AB  - Alterations in energy metabolism play a major role in cancer development.
      Aconitase (ACO2) is an essential enzyme located in the mitochondria and catalyzes
      the interconversion of citrate and isocitrate in the tricarboxylic acid cycle.
      Recent studies suggest that the expression of ACO2 may be altered in certain
      types of cancer. The purpose of this study was to examine ACO2 expression in
      clinical tumor specimens from patients with gastric cancer and to evaluate the
      clinical relevance of ACO2 expression in gastric cancer. A total of 456 paraffin
      embedded gastric cancer tissues and 30 pairs of freshly frozen tissues were used
      in this study. Real-time quantitative reverse transcription polymerase chain
      reaction, western blotting, and immunohistochemical staining were performed to
      measure ACO2 expression in tumor tissues and matched adjacent non-tumorous
      tissues. The results showed that the expression of ACO2 was significantly down
      regulated in gastric cancer tissues compared with matched adjacent nontumorous
      tissues and was associated with clinical stage (p = 0.001), T classification (p =
      0.027), N classification (p = 0.012), M classification (p = 0.002), and
      pathological differentiation states (p = 0.036). Patients with lower ACO2
      expression had a shorter survival time than those with higher ACO2 expression.
      Univariate and multivariate analyses indicated that ACO2 expression functions as
      an independent prognostic factor (p < 0.001). Our data suggested that ACO2 could
      play an important role in gastric cancer and may potentially serve as a
      prognostic biomarker.

PMID- 23550274
TI  - The relationship between brain oscillatory activity and therapeutic effectiveness
      of transcranial magnetic stimulation in the treatment of major depressive
      disorder.
AB  - Major depressive disorder (MDD) is marked by disturbances in brain functional
      connectivity. This connectivity is modulated by rhythmic oscillations of brain
      electrical activity, which enable coordinated functions across brain regions.
      Oscillatory activity plays a central role in regulating thinking and memory,
      mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal
      oscillatory patterns is associated with effective treatment of MDD. Repetitive
      transcranial magnetic stimulation (rTMS) is a robust treatment for MDD, but the
      mechanism of action (MOA) of its benefits for mood disorders remains incompletely
      understood. Benefits of rTMS have been tied to enhanced neuroplasticity in
      specific brain pathways. We summarize here the evidence that rTMS entrains and
      resets thalamocortical oscillators, normalizes regulation and facilitates
      reemergence of intrinsic cerebral rhythms, and through this mechanism restores
      normal brain function. This entrainment and resetting may be a critical step in
      engendering neuroplastic changes and the antidepressant effects of rTMS. It may
      be possible to modify the method of rTMS administration to enhance this MOA and
      achieve better antidepressant effectiveness. We propose that rTMS can be
      administered: (1) synchronized to a patient's individual alpha frequency (IAF),
      or synchronized rTMS (sTMS); (2) as a low magnetic field strength sinusoidal
      waveform; and, (3) broadly to multiple brain areas simultaneously. We present
      here the theory and evidence indicating that these modifications could enhance
      the therapeutic effectiveness of rTMS for the treatment of MDD.

PMID- 23550276
TI  - Overexpression of TFIIB-related factor 2 is significantly  correlated with tumor
      angiogenesis and poor survival in patients  with esophageal squamous cell cancer.
AB  - Studies have shown that genetic activation of TFIIB-related factor 2 (BRF2)
      represents a unique mechanism of tumorigenesis through the increase in Pol III
      mediated transcription. Several studies have shown that BRF2 is overexpressed in
      several types of cancer and suggest the oncogenic role of BRF2. This study aimed
      to examine the expression of TFIIB-related factor 2 (BRF2) in patients with
      esophageal squamous cell cancer (ESCC) and explore the relationship of BRF2
      expression with clinicopathologic factors, tumor angiogenesis and prognosis. We
      found that increased BRF2 protein expression was prevalent in esophageal squamous
      cell cancer and was significantly associated with deeper tumor invasion (P =
      0.039) and microvessel density (P = 0.007). Additionally, expression of BRF2 was
      found to be an independent prognostic factor in ESCC patients. Furthermore, a
      significant correlation between high BRF2 expression and shorter overall survival
      time was found in different subgroups of ESCC patients stratified by the clinical
      stage, T classification and lymph node metastasis. High expression of BRF2
      protein is closely associated with tumor progression and angiogenesis and poor
      survival of ESCC. BRF2 is a promising biomarker to identify individuals with poor
      prognostic potential and concludes the possibility of its use as a prognostic
      marker in patients with ESCC.

PMID- 23550277
TI  - Treatment of peripheral T cell lymphoma with an intensive protocol ACEP
      (adriamycin, cyclophosphamide, etoposide and prednisolone) and ifosfamide showing
      an important response and overall survival rates.
AB  - Peripheral T Cell Lymphoma (PTCL) is a group of lymphoid malignancies which has
      never been treated with any confidence as opposed to its counterpart B Cell
      Lymphomas. Despite the studies, which were retrospective, the results in the
      majority of cases were disappointing, taking into consideration the aggressive
      clinical course of the disease, so survival did not exceed 2 years in median. To
      assess the response, progression-free survival and overall survival rates at 5
      years using a new intensive combination chemotherapy. Enrolled patients were
      diagnosed with PTCL, confirmed by a referenced pathologist, treated with the new
      chemotherapy ACEP X 6 (Doxorubicine 75 mg/m2 on day 1 + Cyclophosphamide 1,200
      mg/m2 on day 1 + Etoposide 300 mg/m2 on day 1 and Prednisolone 60 mg/m2 from day
      1 through day 5) and Ifosfamide X 4 (Ifosfamide 4 grams/m2 on day 1) which were
      given after the completion of the first 6 cycles of ACEP. The study was performed
      at Al-Bairouni University Hospital, and the study was approved by the Syrian
      Association of Clinical Oncology. Twenty-five patients underwent the treatment.
      Most of them showed a complete response after the completion of the first six
      cycles (17/25) forming 68 % of patients, while another 5 patients became complete
      responders after the completion of treatment. Consequently, 22 patients are still
      living after 5 years, with an overall survival rate of 88 %. (ACEP) and
      Ifosfamide appears to be a good choice in PTCLs, in light of the good response
      and overall survival rates, taking into account the acceptable toxicity profile.
      However, a larger sample is needed to make it an acceptable new combination
      chemotherapy for PTCLs patients.

PMID- 23550279
TI  - Reply to Gibb and Hills: Divergence times, generation lengths and mutation rates
      in great apes and humans.

PMID- 23550278
TI  - Inverse correlation between Naa10p and MMP-9 expression  and the combined
      prognostic value in breast cancer patients.
AB  - To analyze the expression profiles of N-a-acetyltransferase 10 protein
      (Naa10p/ARD1) and matrix metalloproteinase 9 (MMP-9) in human breast cancer and
      evaluate their possible prognostic values in breast cancer patients. Quantitative
      RT-PCR was used to evaluate mRNA expression of Naa10p and MMP-9 in 55 cases of
      fresh breast cancer tissues, and immunohistochemistry was performed for detecting
      Naa10p and MMP-9 proteins on breast cancer with tissue microarray containing 80
      specimens. Furthermore, Naa10p and MMP-9 were measured in 253 breast cancer
      tissues from patients with up to 15-year follow-up. Survival curves were
      generated using the Kaplan-Meier method. Multivariate analysis was performed by
      using the Cox proportional hazard regression model to assess the prognostic
      values of Naa10p and MMP-9. Both Naa10p and MMP-9 expression in breast cancer
      tissues were significantly higher than those in the matched non-cancerous tissues
      (p = 0.000 for both). There was an inverse correlation between Naa10p and MMP-9
      expression at mRNA and protein levels (p = 0.000 for both). Patients with MMP-9-
      positive expression had a poorer overall survival (OS) and disease-free survival
      (DFS) than those with MMP-9-negative expression (p = 0.001 for both). However,
      patients with Naa10p-positive expression had better OS and DFS (p = 0.000 for
      both). In addition, Naa10p-positive/MMP-9- negative patients had the best OS and
      DFS (p = 0.000 for both). In multivariate survival analysis, TNM stage, Naa10p
      expression, MMP-9 expression, and combined expression status of Naa10p/MMP-9 were
      independent prognostic factors related to OS (p = 0.000, 0.007, 0.012, and 0.000,
      respectively) and DFS (p = 0.000, 0.002, 0.014, and 0.000, respectively).The
      expression level of Naa10p was inversely correlated with that of MMP-9 in human
      breast cancer samples. Combined analysis of Naa10p and MMP-9 had a significantly
      increased value for determining the prognosis of breast cancer patients.

PMID- 23550280
TI  - Abstracts of Collaborating Across Borders III (CAB III). November 19-21, 2011.
      Tucson, Arizona, USA.

PMID- 23550281
TI  - Abstracts of the European Congress on Osteoporosis and Osteoarthritis. April 17
      20, 2013. Rome, Italy.

PMID- 23550282
TI  - Plastic waste is all at sea.

PMID- 23550283
TI  - Dov Sagi.

PMID- 23550284
TI  - Response.

PMID- 23550285
TI  - Response.

PMID- 23550286
TI  - Intra-articular risks of suprapatellar nailing.
AB  - To determine the risks to local anatomy near the starting point for tibial
      nailing during suprapatellar nailing, 15 fresh-frozen hemipelvis specimens were
      nailed using a suprapatellar technique. After nail passage, the menisci and
      articular surfaces, anterior cruciate ligament (ACL) insertion, intermeniscal
      ligament, and fat pad were assessed for injury. The distance from the entry
      portal to the menisci, articular surfaces, and ACL insertion was determined.
      Medial meniscus injury occurred in 1 (6.7%) specimen and medial articular injury
      in 2 (13%). Nails passed through the fat pad in all specimens; intermeniscal
      ligament injury occurred in 3 (20%) specimens. The ACL insertion and lateral
      structures were not injured in any specimen. The distance from the entry portal
      margin to the lateral and medial menisci was 6.46+/-2.47 mm and 4.74+/-3.17 mm,
      respectively. The distances to the lateral and medial articular margins measured
      10.33+/-3.62 mm and 6.54+/-3.57 mm, respectively. The distance to the ACL
      insertion averaged 5.80+/-3.94 mm. Suprapatellar nailing is associated with a
      risk of injury to anterior knee structures comparable to other nailing
      techniques. Additional clinical studies are warranted to further define the role
      of this technique in the management of tibial fractures.

PMID- 23550287
TI  - Response.

PMID- 23550288
TI  - Response.

PMID- 23550289
TI  - IEEE Transactions on Visualization and Computer Graphics. Message from the editor
      in-chief.

PMID- 23550290
TI  - Learning to reach for "invisible" visual input.

PMID- 23550291
TI  - IEEE Transactions on Visualization and Computer Graphics. Message from the paper
      chairs and guest editors.

PMID- 23550292
TI  - [Tubal dilatation].

PMID- 23550293
TI  - Mesh vs. non-mesh repair for inguinal hernias in emergency operations.
AB  - BACKGROUND/AIMS: Prosthetic repair has become the gold standard for elective
      management of inguinal hernias; however, its use in the setting of acute
      incarceration is still limited for fear of prosthetic-related complications,
      mainly infection. Thus, in this study. we conducted a comparative investigation
      of the outcomes of prosthetic repair vs. tissue repair in the management of
      incarcerated inguinal hernias. METHODOLOGY: We retrospectively analyzed 62
      patients who underwent emergency operations for incarceration of an inguinal
      hernia. These patients were divided into 2 groups based on the surgical procedure
      used: a mesh repair group (M group) and a non-mesh repair group (N group).
      RESULTS: There were no significant differences between the 2 groups with respect
      to postoperative complications and the mean period of post-operative
      hospitalization. CONCLUSIONS: Contrary to traditional belief, the use of a
      prosthetic mesh in the emergency setting is not contra-indicated. Its usage for
      the repair of incarcerated inguinal hernias appears to be safe and acceptable.
      However, when perforation of the intestine occurs due to incarceration of an
      inguinal hernia, prosthetic repair using hernioplasty should not be performed
      because of the high risk of infection.

PMID- 23550294
TI  - [Surgical techniques. Stapes surgery - stapedectomy].

PMID- 23550295
TI  - [Author reply].

PMID- 23550296
TI  - [Author reply].

PMID- 23550297
TI  - Response to letter regarding article, "magnetic resonance imaging with 3
      dimensional analysis of left ventricular remodeling in isolated mitral
      regurgitation: implications beyond dimensions".

PMID- 23550298
TI  - Trans-Atlantic debate: Debate whether fenestrated endografts should be limited to
      a small number of specialized centers.

PMID- 23550299
TI  - Debate whether fenestrated endografts should be limited to a small number of
      specialized centers.

PMID- 23550300
TI  - Reply: To PMID 22922212.

PMID- 23550301
TI  - [Abstracts of French Language Neurology Days. April 9-11, 2013].

PMID- 23550302
TI  - Chronic eosinophilic leukemia with FIP1L1-PDGFRA.

PMID- 23550304
TI  - Real-time responses to severe influenza outbreaks.

PMID- 23550303
TI  - BAP1 and cancer.
AB  - BAP1 is a deubiquitylase that is found associated with multiprotein complexes
      that regulate key cellular pathways, including the cell cycle, cellular
      differentiation, cell death, gluconeogenesis and the DNA damage response (DDR).
      Recent findings indicate that germline BAP1 mutations cause a novel cancer
      syndrome that is characterized, at least in the affected families that have been
      studied so far, by the onset at an early age of benign melanocytic skin tumours
      with mutated BAP1, and later in life by a high incidence of mesothelioma, uveal
      melanoma, cutaneous melanoma and possibly additional cancers.

PMID- 23550305
TI  - Faecal transplantation for recurrent C difficile diarrhoea.

PMID- 23550306
TI  - Reply to VI Kraak et al.

PMID- 23550307
TI  - Reply to Z Weizman.

PMID- 23550308
TI  - Reply to E Giovannucci.

PMID- 23550309
TI  - Right subclavian artery thrombosis due to cervical rib.

PMID- 23550310
TI  - Albert Schweitzer (1875-1965).

PMID- 23550311
TI  - Got ketone strips?

PMID- 23550312
TI  - Low (and behold).

PMID- 23550313
TI  - Destination A1C. Finding a path to your specific blood glucose goals.

PMID- 23550314
TI  - Numbers game. Type 1 baseball player Sam Fuld scores big.

PMID- 23550315
TI  - Clutter busting. Organize your home for better health.

PMID- 23550316
TI  - Body wars. Skipping meals, purging food, avoiding insulin--the scary world of
      eating disorders and diabetes.

PMID- 23550317
TI  - Gather steam.

PMID- 23550318
TI  - [Study on effect of intensive treatment for refractory chronic hepatitis C
      patients].
AB  - OBJECTIVE: To explore the effect of intensive treatment for refractory chronic
      hepatitis C, and to improve the sustained viral response (SVR) rate of treatment
      with interferon plus ribavirin by optimizing therapeutic dose and course.
      METHODS: Patients who did not acquire response or partial response by standard
      therapy (PEG-IFN alpha subcutaneous injection weekly plus Ribavirin 10.5 mg/kg)
      every day were enrolled and retreated with intensive treatment of 10 MU
      interferon every other day or 360 microg pegylated interferon alpha-2a weekly
      according to patients' wishes, and ribavirin 15 mg/kg every day. Serum HCV RNA
      was detected at baseline,treatment week 4, 12 and every 12 weeks succedent and 24
      weeks after treatment end. Course of treatment was 72 to 96 weeks according to
      viral response. SVR was the mark of therapeutic effect. RESULTS: 18 patients
      completed whole range therapy and follow-up, in which 12 patients acquired SVR, 5
      patients treatment failure and 1 relapse. 3 patients acquired rapid viral
      response (RVR), and they all got complete Early Viral Response (cEVR) and SVR.
      RVR Patients' viral loads were significantly lower than that of patients who did
      not acquire RVR (t = 4. 687, P < 0.001). In 15 patients who did not acquire RVR,
      8 patients acquired cEVR, and 9 acquired SVR. SVR rate of patients who were
      administered PEG-IFN alpha-2a was 4/5, 11 patients who acquired cEVR all acquired
      SVR, while in 7 patients who did not acquire cEVR, only 1 patient acquired SVR.
      CONCLUSIONS: High percent patients, who did not acquire response or partial
      response by previous standard antiviral therapy, could gain SVR by intensive dose
      interferon plus Ribavirin. In intensive treatment procedure, adjusting and
      prolonging course according to viral response after HCV RNA turned negative were
      important measures to improve refractory Chronic Hepatitis C SVR rate.

PMID- 23550320
TI  - Retraction statement.

PMID- 23550319
TI  - Resident rounds. Part III: Neutrophilic eccrine hidradenitis in the setting of
      acute myelogenous leukemia treated with cytarabine.

PMID- 23550321
TI  - Limited English proficient HMO enrollees remain vulnerable to communication
      barriers despite language assistance regulations.
AB  - HMO enrollees with limited English proficiency, and particularly those in poorer
      health, face communication barriers despite language assistance regulations. More
      than 1.3 million California HMO enrollees ages 18 to 64 do not speak English well
      enough to communicate with medical providers and may experience reduced access to
      high-quality health care if they do not receive appropriate language assistance
      services. Based on analysis of the 2007 and 2009 California Health Interview
      Surveys (CHIS), commercial HMO enrollees with limited English proficiency (LEP)
      in poorer health are more likely to have difficulty understanding their doctors,
      placing this already vulnerable population at even greater risk. The analysis
      also uses CHIS to examine the potential impact of health plan monitoring starting
      in 2009 (due to a 2003 amendment to the Knox-Keene Health Care Services Act)
      requiring health plans to provide free qualified interpretation and translation
      services to HMO enrollees. The authors recommend that California's health plans
      continue to incorporate trained interpreters into their contracted networks and
      delivery systems, paying special attention to enrollees in poorer health. The
      results may serve as a planning tool for health plans, providing a detailed
      snapshot of enrollee characteristics that will help design effective programs now
      and prepare for a likely increase in insured LEP populations in the future, as
      full implementation of the Affordable Care Act takes place over the next decade.

PMID- 23550322
TI  - National Critical Care Competency Framework.

PMID- 23550323
TI  - How Colorado, Minnesota, and Vermont are reforming care delivery and payment to
      improve health and lower costs.
AB  - Colorado, Minnesota, and Vermont are pioneering innovative health care pay-ment
      and delivery system reforms. While the states are pursuing different models, all
      three are working to align incentives between health care payers and providers to
      better coordi-nate care, enhance prevention and disease management, reduce
      avoidable utilization and total costs, and improve health outcomes. Colorado and
      Minnesota are implementing accountable care models for Medicaid beneficiaries,
      while Vermont is pursuing multipayer approaches and moving toward a unified
      health care budget. This synthesis describes the common drivers of reform across
      the states, lessons learned, and opportunities for federal administrators to help
      shape, support, and promote expansion of promising state initiatives. It also
      synthesizes strategies and lessons for other states considering payment and
      delivery reforms. The accompanying case studies describe the states' efforts in
      greater detail.

PMID- 23550324
TI  - Unintended pregnancy and abortion in Uganda.
AB  - Unintended pregnancy is common in Uganda, leading to high levels of unplanned
      births, unsafe abortions, and maternal injury and death. Because most pregnancies
      that end in abortion are unwanted, nearly all ill health and mortality resulting
      from unsafe abortion is preventable. This report summarizes evidence on the
      context and consequences of unintended pregnancy and unsafe abortion in Uganda,
      points out gaps in knowledge, and highlights steps that can be taken to reduce
      levels of unintended pregnancy and unsafe abortion, and, in turn, the high level
      of maternal mortality.

PMID- 23550325
TI  - Data in search of a principle: a review of relational frame theory: a post
      Skinnerian account of human language and cognition.
AB  - Responding to derived relations among stimuli and events is the subject of an
      accelerating research program that represents one of the major behavior analytic
      approaches to complex behavior. Relational Frame Theory: A Post-Skinnerian
      Account of Human Language and Cognition (Hayes, Barnes-Holmes,& Roche, 2001)
      offers a conceptual framework for this work and explores its implications for
      verbal behavior and a variety of other domains of complex human behavior. The
      authors dismiss Skinner's interpretation of verbal behavior as unproductive and
      conceptually flawed and suggest a new definition and a new paradigm for the
      investigation of verbal phenomena. I found the empirical phenomena important but
      the conceptual discussion incomplete. A new principle of behavior is promised,but
      critical features of this principle are not offered. In the absence of an
      explicit principle,the theory itself is difficult to evaluate. Counter examples
      suggest a role for mediating behavior,perhaps covert, thus raising the question
      whether a new principle is needed at all. The performance of subjects in
      relational frame experiments may be a mosaic of elementary behavioral units, some
      of which are verbal. If so, verbal behavior underlies relational behavior; it is
      not defined by it. I defend Skinner's definition of verbal behavior and argue
      that an account of relational behavior must be integrated with Skinner's
      analysis; it will not replace it.

PMID- 23550326
TI  - Retraction. The nursing rounds system: effect of patient's call light use, bed
      sores, fall and satisfaction level.

PMID- 23550327
TI  - Self-etch and etch-and-rinse adhesive systems in clinical dentistry.
AB  - Current adhesive systems follow either an "etch-and-rinse" or "self-etch"
      approach, which differ in how they interact with natural tooth structures. Etch
      and-rinse systems comprise phosphoric acid to pretreat the dental hard tissues
      before rinsing and subsequent application of an adhesive. Self-etch adhesives
      contain acidic monomers, which etch and prime the tooth simultaneously. Etch-and
      rinse adhesives are offered as two- or three-step systems, depending on whether
      primer and bonding are separate or combined in a single bottle. Similarly, self
      etch adhesives are available as one- or two-step systems. Both etch-and-rinse and
      self-etch systems form a hybrid layer as a result of resins impregnating the
      porous enamel or dentin. Despite current trends toward fewer and simpler clinical
      application steps, one-step dentin bonding systems exhibit bonding agent lower
      bond strengths and seem less predictable than multi-step etch-and-rinse and self
      etch systems. The varying evidence available today suggests that the choice
      between etch-and-rinse and self-etch systems is often a matter of personal
      preference. In general, however, phosphoric acid creates a more pronounced and
      retentive etching pattern in enamel. Therefore, etch-and-rinse bonding systems
      are often preferred for indirect restorations and when large areas of enamel are
      still present. Conversely, self-etch adhesives provide superior and more
      predictable bond strength to dentin and are, consequently, recommended for direct
      composite resin restorations, especially when predominantly supported by dentin.

PMID- 23550328
TI  - Fixed prosthodontics provisional materials: making the right selection.
AB  - Clinicians have many choices when selecting an appropriate material for interim
      restorations for both single crowns and multi-units. Interim restorations serve
      as a diagnostic as well as biologic and biomechanical component of fixed
      prosthodontics treatment; in the anterior, they are also important in evaluating
      the esthetics for the definitive restoration. Factors to be considered when
      choosing provisional materials are physical properties, handling characteristics,
      patient response to the appearance of the interim restoration, durability of the
      restoration, and the cost of the material. Practitioners should, therefore, base
      their choice on the clinical needs for each situation.

PMID- 23550329
TI  - Purposeful exposure of a polylactic acid barrier to achieve socket preservation
      for placement of dental implants: case series report.
AB  - This retrospective case series reports on the use of a polylactic acid barrier
      that was left exposed in the process of socket preparation for the placement of
      dental implants. A retrospective chart review found 43 patients with 48
      extraction sockets that were treated in this manner. Teeth were removed and the
      sockets were thoroughly debrided, with 40 of them receiving a bone replacement
      graft covered by the polylactic acid barrier and the additional 8 receiving the
      membrane alone. Suturing left the barrier exposed, and the sites were re-entered
      on average at 23 weeks for the placement of a dental implant. All sites were able
      to receive a dental implant, demonstrating the ability to leave a polylactic acid
      barrier exposed and achieve successful guided bone regeneration (GBR) results.
      This ultimately helped avoid some of the negative sequelae of trying to achieve
      primary closure of the flaps at the time of tooth extraction.

PMID- 23550330
TI  - Cementation of indirect restorations: an overview of resin cements.
AB  - The process of ensuring proper retention, marginal seal, and durability of
      indirect restorations depends heavily on effective cementation. Careful
      consideration must be made when selecting an adhesive cement for a given
      application. This article provides information on resin cements that can guide
      clinicians in determining which type of cement is best suited to their clinical
      needs regarding cementation of indirect restorations. Emphasis is placed on
      successful cementation of all-ceramic restorations.

PMID- 23550331
TI  - Composite resins in 2013: an update on their progress.
AB  - Having steadily evolved and improved over the past several decades, composite
      resins are providing clinicians with an increased array of options for
      successfully restoring teeth in a minimally invasive manner. Numerous advances
      compared to early composite resin systems, such as increased shade availability,
      reduced polymerization shrinkage, and the development of nanoparticles, have
      enabled composite resins to offer long-term esthetic solutions for patients. This
      article summarizes the changes that have occurred, discusses popular applications
      for the use of composite materials, and presents brief case studies demonstrating
      their capabilities.

PMID- 23550332
TI  - Strategies for integrating new restorative materials with digital technology and
      sound restorative principles.
AB  - Restorative dental materials have experienced a significant evolution over the
      past 40 years. The pace of change has especially accelerated in the past decade,
      while, concurrently, advances in implant technology and digital dentistry have
      paralleled this rapid growth. This article outlines the strengths and weaknesses
      of various popular ceramic restorative materials and how today's technology can
      be effectively utilized to fabricate these materials into exceptional
      restorations.

PMID- 23550333
TI  - Comparison of mechanical properties of five commercial dental core build-up
      materials.
AB  - OBJECTIVE: This study aimed to evaluate and compare the mechanical properties of
      five commercial core materials using fracture toughness (FT), Knoop hardness
      number (KHN), diametral tensile strength (DTS), and dynamic elastic moduli (DEM).
      METHODS: Composite material specimens were produced (Rock Core, CosmeCore,
      ParaCore, MultiCore Flow, and Filtek Supreme Plus). The FT test (n = 15) was
      performed using notchless triangular prism (NTP) specimens. FT was determined
      using an Instron testing machine. KHN (n = 3) was evaluated using three
      indentations applied on each specimen. DTS test (n = 15) was measured using an
      Instron testing machine. The density. of the specimens (n = 3) was determined by
      water displacement method. Dynamic Young's, shear moduli, and Poisson's ratio (n
      = 3) were measured by an ultrasonic method. Statistical analysis was conducted
      using ANOVA and a Tukey B rank order test (P = 0.05). RESULTS: Rock Core
      presented the lowest FT values. Filtek Supreme Plus and CosmeCore exhibited
      significantly higher KHN values than the rest of the materials. CosmeCore had the
      highest DTS value, which was statistically significant only compared to Rock
      Core. For DEM, Filtek Supreme Plus exhibited significantly higher Young's and
      shear moduli than the rest of the materials (P < 0.05). CONCLUSIONS: Results
      demonstrated significant differences in the FT, KHN, and DTS values of the core
      build-up materials tested. According to the elastic behavior of the core
      composite materials, Rock Core had the lowest Young's values.

PMID- 23550334
TI  - Dentistry's proactive role in preventing disease.

PMID- 23550335
TI  - Array of Crosstex products helping clinicians maintain sterility standards.

PMID- 23550336
TI  - DenMat, LED dental's VELscope Vx: saving lives by detecting oral cancer early.

PMID- 23550337
TI  - Nature vs. nurture: gold perpetuates "stemness".
AB  - Adult tissues contain quiescent reservoirs of multipotent somatic stem cells and
      pluripotent embryonic-like stem cells (ELSCs). Credited with regenerative
      properties gold is used across both -contemporary and -ancient medicines. Here,
      we show that gold exerted these effects by enhancing the pool of pluripotent ELSC
      while improving their stemness. We used hESCs as an in-vitro model to understand
      if gold could enhance self-renewal and pluripotency. Swarna-bhasma (SB), an
      ancient Indian gold microparticulate (41.1 nm), preparation, reduced spontaneous
      differentiation, improved self-renewal, pluripotency and proliferation of hESCs.
      Colloidal gold-nanoparticles (GNP) (15.59 nm) were tested to confirm that the
      observations were attributable to nanoparticulate-gold. SB and GNP exposure:
      maintained -stemness, -karyotypic stability, enhanced pluripotency till day-12,
      increased average colony-sizes, and reduced the number of autonomously-derived
      differentiated FGFR1 positive fibroblast-niche-cells/colony. Particulate-gold
      induced upregulation of FGFR1 and IGF2 expression, and decrease in IGF1 secretion
      indicates IGF1/2 mediated support for enhanced pluripotency and self-renewal in
      hESCs.

PMID- 23550338
TI  - Genetic stability of murine pluripotent and somatic hybrid cells may be affected
      by conditions of their cultivation.
AB  - Using mouse pluripotent teratocarcinoma PCC4azal cells and proliferating spleen
      lymphocytes we obtained a new type of hybrids, in which marker lymphocyte genes
      were suppressed, but expression the Oct-4 gene was not effected; the hybrid cells
      were able to differentiate to cardiomyocytes. In order to specify the
      environmental factors which may affect the genetic stability and other hybrid
      properties, we analyzed the total chromosome number and differentiation potencies
      of hybrids respectively to conditions of their cultivation. Particular attention
      was paid to the number and transcription activity of chromosomal nucleolus
      organizing regions (NORs), which harbor the most actively transcribed - ribosomal
      - genes. The results showed that the hybrids obtained are characterized by a
      relatively stable chromosome number which diminished less than in 5% during 27
      passages. However, a long-term cultivation of hybrid cells in non-selective
      conditions resulted in preferential elimination of some NO- chromosomes, whereas
      the number of active NORs per cell was increased due to activation of latent
      NORs. On the contrary, in selective conditions, i.e. in the presence of
      hypoxantine, aminopterin and thymidine, the total number of NOR-bearing
      chromosomes was not changed, but a partial inactivation of remaining NORs was
      observed. The higher number of active NORs directly correlated with the
      capability of hybrid cells for differentiation to cardiomyocytes.

PMID- 23550339
TI  - Molecular mechanism involved in the maintenance of pluripotent stem cells.
AB  - The idea of growing human cells in vitro to yield a renewable source of cells for
      transplantation has captured the imagination of scientists for many years. The
      derivation of human embryonic stem cells (hESC) represented a major milestone in
      achieving this goal. hESC are pluripotent and can proliferate in vitro
      indefinitely, rendering them an ideal source for cell replacement therapy.
      Moreover, recent advances in reprogramming somatic cells into induced pluripotent
      stem cells (iPS cells) have enabled us to unravel some of the key master
      regulators of stem cell pluripotency. By integrating recent findings of molecular
      mechanism involved in maintenance of these different pluripotent stem cell types,
      we aim to present a global picture of how extracellular signals, intracellular
      signal transduction pathways and transcriptional networks cooperate together to
      determine the cell fate of pluripotent stem cells. Unraveling the signaling
      networks that control stem cell pluripotency will be helpful in deriving novel
      methods to maintain these pluripotent stem cells in vitro.

PMID- 23550340
TI  - Exploring a stem cell basis to identify novel treatment for human malignancies.
AB  - Research investigations on various sources of stem cells have been conducted for
      potential to exert tissue regeneration, reverse immune-enhancement, and protect
      against tissue insult. At a more distant goal, it is likely that stem cells could
      be applied to medicine via organogenesis. However, the field of stem cells is not
      new since immune replacement via bone marrow transplantation is considered a
      successful form of cell therapy. There is evidence that stem cell therapies are
      close for several disorders such as neurodegeneration, immune hyperactivity, and
      functional insufficiencies such as Type I diabetes mellitus. The field of stem
      cell biology is gaining a strong foothold in science and medicine as the
      molecular mechanisms underlying stem cell behavior are gradually being unraveled.
      Although stem cells have tremendous therapeutic applicability in the
      aforementioned conditions, their uniqueness may also confer adverse properties,
      rendering them a double-edged sword. The discovery that stem cells have immortal
      and resilient characteristics has shed insight into the link between stem cells
      and tumorigenesis. Specifically, recent advancements in cancer research have
      implicated that a stem cell may be responsible for the refractoriness of cancers
      to conventional treatment such as chemotherapy and radiation. Here, we summarize
      the recent advancements in the cancer stem cell hypothesis and present the
      challenges associated with targeting resistant cancers in the context of stem
      cell microenvironments.

PMID- 23550341
TI  - Induced pluripotent stem cell-derived hepatocytes as an alternative to human
      adult hepatocytes.
AB  - Recent advances in induced pluripotent stem (iPS) cell research have attracted
      much attention. The ability to generate such cells from somatic cells has
      implications for overcoming both immunological rejection and the ethical issues
      associated with embryonic stem (ES) cells. Hepatocytes derived from patient
      specific iPS cells offer a possible solution to the shortage of cell sources in
      cell replacement therapy, drug screening, and disease model. Despite such great
      promise, however, recent articles have questioned the viability of the
      therapeutic applications of iPS cells. These cells must, therefore, satisfy
      stringent criteria prior to practical use. The main focus of this review is a
      description of the current status of hepatic differentiation technology of iPS
      cells and a discussion of the concerns regarding the practical use of these
      techniques in cell replacement therapy, drug screening, and disease model. The
      current status of strategies for generating iPS cells and the accumulated
      knowledge on strategies for differentiating ES cells into hepatocytes will be
      summarized. We also refer to the possibility of direct conversion of adult
      somatic cells into functional hepatocytes.

PMID- 23550342
TI  - Morphogenesis of Drosophila melanogaster macrochaetes: cell fate determination
      for bristle organ.
AB  - Formation of specialized spatial structures comprising various cell types is most
      important in the ontogenesis of multicellular organisms. An example is the D.
      melanogaster bristle organs. Bristles (micro- and macrochaetes) are external
      sensory organs, elements of the peripheral nervous system, playing the role of
      mechanoreceptors. Their comparatively simple organization comprising only four
      specialized cells and a common origin of these cells make macrochaetes a
      convenient model for studying cell differentiation. The four cells forming
      bristle organ result from two successive divisions of a single cell, sensory
      organ precursor (SOP) cell. The number of macrochaetes on drosophila body
      corresponds to the number of SOP cells. The morphogenesis of macrochaetes
      comprises three stages, the first two determining a neural fate of the cells. The
      third stage is cell specialization into components of the bristle organ-neuron,
      thecogen, tormogen, and trichogen. Development of each bristle commences from
      segregation of proneural clusters, of 20-30 cells, from the massif of
      undifferentiated cells of the wing imaginal disc. At this stage, each cluster
      cell can potentially become a SOP cell. At the second stage, the only SOP cell
      and its position are determined within each cluster. Finally, two asymmetric
      divisions of the SOP cell with subsequent differentiation of the daughter cells
      gives the bristle organ. Several dozens genes are involved in the control of
      macrochaete morphogenesis. The main component of this system is the proneural
      genes of achaete-scute complex (AS-C). An increased content of proneural proteins
      fundamentally distinguished the cells that will follow the neural developmental
      pathway from the disc epidermal cells. A local AS-C expression, initiated at
      specified disc sites by specific transcription factors, determines the number and
      topology of proneural clusters. The expression of AS-C genes, continuing in the
      cells of the cluster, increases the difference in proneural protein content,
      first, between the cluster cells and then, between the cluster cells and the
      single SOP cell, where it reaches the maximum level. This process is provided by
      both the intracellular regulation of AS-C gene activity and intercellular events
      mediated via the EGFR and Notch signaling pathways. The third stage in
      macrochaete morphogenesis comprises two successive asymmetric SOP cell divisions,
      determining the final specialization. The selector genes, in particular, numb,
      neuralized, tramtrack, and musashi, play the key role in cell type specification.
      This review systematizes the data on molecular genetic system controlling
      drosophila bristle morphogenesis and proposes an integral scheme of its
      functioning.

PMID- 23550343
TI  - Benzene exposure--an experimental machinery for induction of myelodysplastic
      syndrome: stem cell and stem cell niche analysis in the bone marrow.
AB  - Human epidemiologic studies of highly exposed occupational cohorts have
      demonstrated that inhalation/exposure to benzene can cause several blood
      disorders, like non-lymphocytic leukemia, pre leukemic stage, aplastic anemia,
      and other related syndromes collectively considered as bone marrow failure
      syndromes. Like many other agents [e.g. chemotherapeutics etc] benzene selects
      the bone marrow as an important target but the exact location and the mechanism
      of damage is yet unexplored. The present study aimed at delineating benzene
      induced myelodysplasia and related disorders in an experimental mouse model with
      a view to assessing the clinical hazards in human at a comparable event. The
      observations made so far documented some quantitative and qualitative changes in
      the bone marrow population, especially involving the hematopoietic stem cells and
      related microenvironment, their immune responsiveness and survival fate of the
      cells at that particular event. The observations furnished that benzene following
      occupational exposure can be hazardous by way of HSC mediated dysfunction and,
      the microenvironmental studies conducted in some details indicated that the
      damage may be in the bone marrow stem cell niche. Furthermore, some data
      collected showed an increased death rate of bone marrow cells and associated
      abnormalities in receptor expression of adhesion molecules and related growth
      factors. Culminating the above data the study reveals that Benzene may cause
      target damage in the bone marrow stem cell niche [BM SC niche] both structurally
      and functionally, with the resultant disease expression as in MDS.

PMID- 23550344
TI  - Sulfatide--a new candidate for ART treatment in HIV-1 infection.
AB  - New combination drug treatment(s) now available to patients with HIV-1 infection
      allows them to live longer lives with good quality of life although they suffer
      from the incurable HIV-1 infection. In a previous study we found that sulfatide
      was efficient in lowering HIV-1 viral loads in SCID mice engrafted with human
      fetal liver/thymus tissues (SCID-hu). Current antiviral treatments carry an
      increased risk of other complications like cardiovascular disease and diabetes
      after long-term use. There is a need for new potent safe pharmaceutical agents.
      Endogenous sulfatide is a mixture of -isoforms, i.e. sulfatide molecules with
      different long-chain bases and fatty acid chain lengths and saturation. Sulfatide
      isoforms may have different physicochemical properties i.e, they are of different
      potency at different target cells. Other investigators have shown that incubation
      of cultured cells with sulfatide incorporated into the plasma membrane inhibited
      HIV-1 entry into the cells thereby inhibiting intracellular HIV-1 replication. We
      have shown that CD1d dependent stimulation by sulfatide may activate pDC antigen
      expressing cells that produce type I inteferons. Type I inteferons are known to
      reduce HIV-1 replication. This could provide a second likely explanation (after
      the inhibition of virus entry) for the more efficient lowering of HIV-1 viral
      loads in sulfatide versus AZT treated mice. This review aims to show the
      efficiency of sulfatide in reducing HIV-1 viral loads as compared to conventional
      HAART treatment. We also discuss the risks of HAART treatment and propose a
      clinical alternative of sulfatide in HIV-1 infection.

PMID- 23550345
TI  - Unanswered questions in musculoskeletal tissue engineering.

PMID- 23550346
TI  - Mesenchymal stem cells, sources of cells and differentiation potential.
AB  - Tissue is frequently damaged or lost in injury and disease. There has been an
      increasing interest in stem cell applications and tissue engineering approaches
      in surgical practice to deal with damaged or lost tissue. Tissue engineering is
      an exciting strategy being explored to deal with damaged or lost tissue. It is
      the science of generating tissue using molecular and cellular techniques,
      combined with material engineering principles, to replace tissue. This could be
      in the form of cells with or without matrices. Although there have been
      developments in almost all surgical disciplines, the greatest advances are being
      made in orthopaedics, especially in cartilage repair. This is due to many factors
      including the familiarity with bone marrow derived mesenchymal stem cells and
      cartilage being a relatively simpler tissue to engineer. Unfortunately
      significant hurdles remain to be overcome in many areas before tissue engineering
      becomes more routinely used in clinical practice. Cells used in tissue
      engineering could be autologous, allogeneic or xenogeneic. The cells could be
      stem cells or cells further down the differentiation pathway. The use of
      embryonic stem cells is associated with religious, political and social concerns,
      but the use of adult stem cells is generally well accepted. Stem cells have been
      identified in a number of adult tissues, albeit in small numbers. In addition to
      bone marrow, mesenchymal stem cells have been identified in a number of tissues
      including adipose tissue and fat pad. The mesenchymal stem cells are generally
      isolated from the tissue and expanded in culture. These cells can be
      differentiated down a particular differentiation pathway e.g. osteoblast or
      chondrocyte, using predefined culture conditions before being used for clinical
      applications. In this paper stem cells are discussed including their various
      sources and their differentiation potential.

PMID- 23550347
TI  - The characterisation of mesenchymal stem cells: a stem cell is not a stem cell is
      not a stem cell.
AB  - There has been an increasing interest in stem cell applications and tissue
      engineering approaches in surgical practice to deal with damaged or lost tissue.
      Although there have been developments in almost all surgical disciplines, the
      greatest advances are being made in orthopaedics. This is due to many factors
      including the familiarity with bone marrow derived mesenchymal stem cells.
      Unfortunately significant hurdles remain to be overcome in many areas before
      tissue engineering becomes more routinely used in clinical practice. Stem cells
      have been identified in a number of adult tissues, albeit in small numbers. In
      addition to bone marrow, mesenchymal stem cells have been identified in a number
      of tissues including adipose tissue and fat pad. The mesenchymal stem cells are
      generally isolated from the tissue and expanded in culture. These cells are
      characterised or defined using a set of cell surface markers; mesenchymal stem
      cells are generally positive for CD44, CD90 and CD105, and are negative for
      haematopoetic markers CD34 and CD45, and the neurogenic marker CD56. In this
      paper the characterisation of stem cells is discussed followed by preliminary
      evidence suggesting that pericytes may be a candidate stem cell.

PMID- 23550348
TI  - Cartilage tissue engineering approaches applicable in orthopaedic surgery: the
      past, the present, and the future.
AB  - Tissue is frequently damaged or lost in injury and disease. There has been an
      increasing interest in stem cell applications and tissue engineering approaches
      in surgical practice to deal with damaged or lost tissue. Although there have
      been developments in almost all surgical disciplines, the greatest advances are
      being made in orthopaedics, especially in cartilage repair. This is due to many
      factors including the familiarity with bone marrow derived mesenchymal stem cells
      and cartilage being a relatively simpler tissue to engineer. Unfortunately
      significant hurdles remain to be overcome in many areas before tissue engineering
      becomes more routinely used in clinical practice. In this paper we discuss the
      structure, function and embryology of cartilage and osteoarthritis. This is
      followed by a review of current treatment strategies for the repair of cartilage
      and the use of tissue engineering.

PMID- 23550349
TI  - Embryonic versus mesenchymal stem cells in cartilage repair.
AB  - As our population changes osteoarthritis and cartilage defects are becoming more
      prevalent. The discovery of stems cells and their ability for indefinite
      regeneration has revolutionised the way cartilage problems are viewed. Tissue
      engineering has been shown to be the ideal way of repairing articular cartilage
      lesions, i.e. back to native tissue. The two main types of stem cells being
      investigated in chondrogenesis are embryological and mesenchymal stem cells.
      Research into embryological stem cells has been surrounded by controversy because
      of tumour formation and damaging embryos during the harvest of cells. We discuss
      the use of embryological and mesenchymal stem cells in cartilage repair and the
      various factors involved in the differentiation into chondrocytes.

PMID- 23550350
TI  - Designing a 'neotissue' using the principles of biology, chemistry and
      engineering.
AB  - The traditional methods of treating musculoskeletal injuries and disorders are
      not completely effective and have several limitations. Tissue engineering
      involves using the principles of biology, chemistry and engineering to design a
      'neotissue' that augments a malfunctioning in vivo tissue. The main requirements
      for functional engineered tissue include reparative cellular components that
      proliferate on a scaffold grown within a bioreactor that provides specific
      biochemical and physical signals to regulate cell differentiation and tissue
      assembly. In this review we provide an overview of the biology of common
      musculoskeletal tissue and discuss their common pathologies. We also describe the
      commonly used stem cells, scaffolds and bioreactors and evaluate their role in
      issue engineering.

PMID- 23550352
TI  - The good the bad & the ugly: what factors differentiate high-quality EMS systems?

PMID- 23550351
TI  - The use of nanotechnology in tendon regeneration and repair.
AB  - Tendon injuries are common and due to their limited capacity for self-healing,
      the biomechanical and functional properties of healed tendon are usually inferior
      to normal tissue. Tissue engineering offers the hope of regenerating tendon
      tissue with the same biomechanical properties of the native undamaged tissue by
      augmenting the regenerative process of in vivo tissue or producing a functional
      tissue in vitro that can be implanted into the defective tendon site. Current
      research on tendon tissue engineering has focused on the role of stem cell and
      tendon derived cell therapy, scaffolds, chemical and physical stimulation and
      gene-therapeutic approaches. In this review we review the important functional
      anatomy and pathomechanics of tendon injury and discuss the current advances in
      tendon tissue engineering.

PMID- 23550353
TI  - The things we say: saving the most precious lives of all.

PMID- 23550354
TI  - Enigmatic rhythm: swift action is key in complex cardiac case.
AB  - This was an interesting, yet enigmatic, case. An elderly male with a prolonged QT
      interval developed a third-degree block with a slow ventricular rate. This
      spontaneously converted to a polymorphic v tach (probably torsades) that worsened
      his cardiac output causing pulmonary congestion and hypoxia. He ultimately
      converted back to a third-degree block following treatment with amiodarone and
      magnesium sulfate. More importantly, paramedics recognized the complexity of the
      case and, because of the very short transport time, elected to rapidly transport
      the patient. Complex cases such as this do not fit into any standardized EMS
      protocol. Because of this, we need paramedics who see and recognize serious
      conditions that don't fall within the constraints of algorithmic protocols. In
      this case, they identified the problem, transported promptly and alerted the
      staffin a busy ED of the patient's complex and deteriorating condition.

PMID- 23550355
TI  - Top of the pyramid: what makes a model EMS system?

PMID- 23550356
TI  - Cool the burn: burn injuries require quick identification, treatment & transport.

PMID- 23550357
TI  - Drowning in care: controversies surrounding IV fluid use in prehospital care of
      critically ill patients.

PMID- 23550358
TI  - The meaning behind 'meaningful use': how EMS is ahead of the curve.

PMID- 23550359
TI  - Secure in the cloud: the new public vs. private debate is in data security.

PMID- 23550360
TI  - Eating healthy on an EMS budget: 8 tips to stretch your budget, not your
      waistline.

PMID- 23550361
TI  - Smart tracking: innovative vehicle programs decrease errors & increase
      efficiency.

PMID- 23550362
TI  - Sudden attack: learn to identify, assess & treat seizures.

PMID- 23550363
TI  - The influence of painting composition on human perception.
AB  - Artists have long explored the way in which we see the world, and they have
      developed their own tools to portray their vision. The present study investigated
      whether the compositional information in paintings, an artistic device invented
      by artists, is utilized when people view paintings. In Experiment 1, we
      categorized paintings depending on their compositions through experts' ratings.
      Using the stimuli from Experiment 1, Experiment 2 tested if the compositional
      information interferes with a target detection task. We found that the false
      alarms increased when the targets and distracters had the same composition
      compared to when they were different. Finally, Experiments 3A and 3B examined
      whether composition information influences the perceptual similarity of
      paintings. Through a multi-dimensional scaling analysis, we first showed that
      paintings with the same composition were proximately located in the mental space
      (Experiment 3A). Using this distance from the MDS analysis, we found that
      performance on the target detection task decreased as this distance became close
      (Experiment 3B). These results suggest that people make use of compositions in
      paintings, thus providing a possible link between artworks and the human visual
      system.

PMID- 23550364
TI  - Features of the human rod bipolar cell ERG response during fusion of scotopic
      flicker.
AB  - The ability of the eye to distinguish between intermittently presented flash
      stimuli is a measure of the temporal resolution of vision. The aim of this study
      was to examine the relationship between the features of the human rod bipolar
      cell response (as measured from the scotopic ERG b-wave) and the psychophysically
      measured critical fusion frequency (CFF). Stimuli consisted of dim (-0.04 Td x
      s), blue flashes presented either singly, or as flash pairs (at a range of time
      separations, between 5 and 300 ms). Single flashes of double intensity (-0.08 Td
      x s) were also presented as a reference. Visual responses to flash pairs were
      measured via (1) recording of the ERG b-wave, and (2) threshold determinations of
      the CFF using a two-alternative forced-choice method (flicker vs. fused
      illumination). The results of this experiment suggest that b-wave responses to
      flash pairs separated by < 100 ms are electrophysiologically similar to those
      obtained with single flashes of double intensity. Psychophysically, the percepts
      of flash pairs < 100 ms apart appeared fused. In conclusion, the visual system's
      ability to discriminate between scotopic stimuli may be determined by the
      response characteristics of the rod bipolar cell, or perhaps by the rod
      photoreceptor itself.

PMID- 23550365
TI  - Contribution of disparity to the perception of 3D shape as revealed by
      bistability of stereoscopic Necker cubes.
AB  - The Necker cube is a famous demonstration of ambiguity in visual perception of 3D
      shape. Its bistability is attributed to indecisiveness because monocular cues do
      not allow the observer to infer one particular 3D shape from the 2D image. A
      remarkable but not appreciated observation is that Necker cubes are bistable
      during binocular viewing. One would expect disparity information to veto
      bistability. To investigate the effect of zero and non-zero disparity on
      perceptual bistability in detail, perceptual dominance durations were measured
      for luminance- and disparity-defined Necker cubes. Luminance-defined Necker cubes
      were bistable for all tested disparities between the front and back faces of the
      cubes. Absence of an effect of disparity on dominance durations suggested the
      suppression of disparity information. Judgments of depth between the front and
      back sides of the Necker cubes, however, showed that disparity affected perceived
      depth. Disparity-defined Necker cubes were also bistable but dominance durations
      showed different distributions. I propose a framework for 3D shape perception in
      which 3D shape is inferred from pictorial cues acting on luminance- and disparity
      defined 2D shapes.

PMID- 23550366
TI  - Depth of field affects perceived depth-width ratios in photographs of natural
      scenes.
AB  - The aim of the study was to find out how much influence depth of field has on the
      perceived ratio of depth and width in photographs of natural scenes. Depth of
      field is roughly defined as the distance range that is perceived as sharp in the
      photograph. Four different semi-natural scenes consisting of a central and two
      flanking figurines were used. For each scene, five series of photos were made, in
      which the distance in depth between the central figurine and the flanking
      figurines increased. These series of photographs had different amounts of depth
      of field. In the first experiment participants adjusted the position of the two
      flanking figurines relative to a central figurine, until the perceived distance
      in the depth dimension equaled the perceived lateral distance between the two
      flanking figurines. Viewing condition was either monocular or binocular (non
      stereo). In the second experiment, the participants did the same task but this
      time we varied the viewing distance. We found that the participants' depth/width
      settings increased with increasing depth of field. As depth of field increased,
      the perceived depth in the scene was reduced relative to the perceived width.
      Perceived depth was reduced relative to perceived width under binocular viewing
      conditions compared to monocular viewing conditions. There was a greater
      reduction when the viewing distance was increased. As photographs of natural
      scenes contain many highly redundant or conflicting depth cues, we conclude
      therefore that local image blur is an important cue to depth. Moreover, local
      image blur is not only taken into account in the perception of egocentric
      distances, but also affects the perception of depth within the scene relative to
      lateral distances within the scene.

PMID- 23550367
TI  - Simultaneous brightness and apparent depth from true colors on grey: Chevreul
      revisited.
AB  - We show that true colors as defined by Chevreul (1839) produce unsuspected
      simultaneous brightness induction effects on their immediate grey backgrounds
      when these are placed on a darker (black) general background surrounding two
      spatially separated configurations. Assimilation and apparent contrast may occur
      in one and the same stimulus display. We examined the possible link between these
      effects and the perceived depth of the color patterns which induce them as a
      function of their luminance contrast. Patterns of square-shaped inducers of a
      single color (red, green, blue, yellow, or grey) were placed on background fields
      of a lighter and a darker grey, presented on a darker screen. Inducers were
      always darker on one side of the display and brighter on the other in a given
      trial. The intensity of the grey backgrounds varied between trials only. This
      permitted generating four inducer luminance contrasts, presented in random order,
      for each color. Background fields were either spatially separated or consisted of
      a single grey field on the black screen. Experiments were run under three
      environmental conditions: dark-adaptation, daylight, and rod-saturation after
      exposure to bright light. In a first task, we measured probabilities of contrast,
      assimilation, and no effect in a three-alternative forced-choice procedure
      (background appears brighter on the 'left', on the 'right' or the 'same'). Visual
      adaptation and inducer contrast had no significant influence on the induction
      effects produced by colored inducers. Achromatic inducers produced significantly
      stronger contrast effects after dark-adaptation, and significantly stronger
      assimilation in daylight conditions. Grouping two backgrounds into a single one
      was found to significantly decrease probabilities of apparent contrast. Under the
      same conditions, we measured probabilities of the inducers to be perceived as
      nearer to the observer (inducers appear nearer on 'left', on 'right' or the
      'same'). These, as predicted by Chevreul's law of contrast, were determined by
      the luminance contrast of the inducers only, with significantly higher
      probabilities of brighter inducers to be seen as nearer, and a marked asymmetry
      between effects produced by inducers of opposite sign. Implications of these
      findings for theories which attempt to link simultaneous induction effects to the
      relative depth of object surfaces in the visual field are discussed.

PMID- 23550368
TI  - The effect of attention on context dependent synesthetic experiences.
AB  - Here we report the results of a brief experiment investigating the role of
      attention in mediating contextual effects on synesthetic experiences.
      Specifically, we examine a grapheme-color synesthete for whom the grapheme letter
      'O' and number '0' are associated with two very different colors. We presented
      the grapheme '0' in an array of graphemes that provided ambiguous contextual
      cues, such that the same grapheme could be perceived either as the number '0' or
      as the letter 'O'. We find that an attentional cue that draws attention to one or
      the other of the contexts biases the perceived synesthetic color of the '0'
      grapheme to that associated with the cued context. This is true even when the
      physical color of the grapheme corresponds to the un-cued context.

PMID- 23550369
TI  - Stimulus meanings alter illusory self-motion (vection)--experimental examination
      of the train illusion.
AB  - Over the last 100 years, numerous studies have examined the effective visual
      stimulus properties for inducing illusory self-motion (known as vection). This
      vection is often experienced more strongly in daily life than under controlled
      experimental conditions. One well-known example of vection in real life is the so
      called 'train illusion'. In the present study, we showed that this train illusion
      can also be generated in the laboratory using virtual computer graphics-based
      motion stimuli. We also demonstrated that this vection can be modified by
      altering the meaning of the visual stimuli (i.e., top down effects). Importantly,
      we show that the semantic meaning of a stimulus can inhibit or facilitate
      vection, even when there is no physical change to the stimulus.

PMID- 23550370
TI  - Effects of stimulus eccentricity on the perception of visually induced self
      motion facilitated by simulated viewpoint jitter.
AB  - The present investigation aimed to examine the effects of stimulus eccentricity
      in the facilitation of vection by a jittering visual inducer. A psychophysical
      experiment revealed that the central region of the visual field is more critical
      in facilitation by perspective viewpoint jitter than the peripheral area. The
      results suggest that the perceptual mechanism underlying the facilitation by
      jitter may be different from that responsible for generating standard vection
      from non-jittering visual motion, because the effects of stimulus eccentricity
      were quite different in these two situations.

PMID- 23550371
TI  - Making sense of scents: the colour and texture of odours.
AB  - The purpose of this study was to document colour and texture associations to
      odours using a variety of odours including both pleasant and unpleasant odours,
      some of which were likely to be unfamiliar. We asked non-synaesthetic adults (n =
      78) to make colour and shape/texture associations to 22 odours. A subset of the
      participants (n = 41) smelled the odours a second time in order to identify them.
      Each odour stimulus was associated consistently to one or more specific colours
      and/or textures (all p's < 0.01 by binomial probability statistics). Associations
      to the four odours that were identified accurately (cinnamon, lemon, peppermint
      and licorice) seemed to be based on learning/memory (e.g. lemon = yellow). The
      associations to the 18 odours that were not identified accurately are less likely
      to be based on learning/memory (e.g. ginger = black, rough, sharp; lavender =
      green, white, liquid, sticky). We speculate that sensory associations to odours,
      like those to pitch and letters (e.g. Mondloch and Maurer, 2004; Spector and
      Maurer, 2008), may result from the joint influence of learning and natural biases
      linking dimensions across sensory systems. Such links may reflect inherent neural
      organization that is modifiable with learning and that can manifest as cross
      modal associations or synaesthetic percepts.

PMID- 23550372
TI  - MANopause (andropause).

PMID- 23550373
TI  - Like nurses, not all midwives are alike.

PMID- 23550374
TI  - Core value 1: Holistic philosophy, theorie and ethics.

PMID- 23550375
TI  - AHNA financial matters 2012.

PMID- 23550376
TI  - A brief introduction to the new Healthy People 2020 initiative.

PMID- 23550377
TI  - Tag! We're it: Holistic nurses as champions for health promotion and self-care.

PMID- 23550378
TI  - Quality of life through the end of life.

PMID- 23550379
TI  - Holistic clinical nurse leader.

PMID- 23550380
TI  - Team-based health care: the physician as quarterback.

PMID- 23550381
TI  - Ovarian vein thrombosis: analysis of patient age, etiology, and side of
      involvement.
AB  - OBJECTIVE: To analyze the age distribution, underlying etiology, and side of
      involvement in patients diagnosed with ovarian vein thrombosis (OVT). METHODS: A
      retrospective study was conducted at Christiana Care Health System to identify
      all patients with an imaging diagnosis of OVT from January 2003 to September
      2010. The data collected on this patient population included patient age,
      etiology, imaging modality used for diagnosis, side of involvement, as well as
      renal vein and inferior vena cava involvement. RESULTS: A total of 26 patients
      were diagnosed with OVT. The age distribution in patients with ovarian vein
      thrombosis ranged from 21 to 91. Ovarian vein thrombosis was diagnosed by
      computed tomography (CT) in 85 percent (22/26) of patients and magnetic resonance
      imaging (MRI) in 15 percent (4/26) of patients. The most common etiologies were
      underlying malignancy (27 percent, 7/26) and non-pregnancy related pelvic surgery
      (23 percent, 6/26). The postpartum state accounted for only 12 percent (3/26) of
      the cases. Thrombosis occurred in left ovarian vein in 50 percent (13/26), in the
      right ovarian vein in 42 percent (11/26), and bilaterally in 8 percent (2/26) of
      patients. Associated thrombus in the left renal vein was observed in 12 percent
      (3/26), and in the inferior vena cava in 15 percent (4/26) of patients.
      CONCLUSION: In our clinical practice, ovarian vein thrombosis is primarily
      diagnosed with computed tomography (CT) and less frequently via magnetic
      resonance imaging (MRI). In contrast to most of the published data, which
      emphasizes occurrence of OVT in women of child bearing age and postpartum state,
      in our series we found it occurred over a broad age distribution. There were a
      wide range of underlying etiologies. Half of the cases of ovarian vein thrombosis
      unilaterally involved the left ovarian vein, unlike the overwhelming right sided
      predominance reported by most other studies.

PMID- 23550382
TI  - The founders of the Medical Society of Delaware: Doctor Robert Cook.

PMID- 23550383
TI  - Opioids for chronic noncancer pain: are they safe and effective?

PMID- 23550384
TI  - Traumatic vulvar hematoma masquerading as a bartholin duct cyst in a
      postmenopausal woman.
AB  - Vulvar hematomas, while typically occurring following vaginal delivery, are
      occasionally seen in the nonpregnant patient following perineal trauma. When
      these, as well as any vulvar mass, are discovered in a postmenopausal woman,
      concern regarding a neoplasm exists. CASE: A 66-year-old woman was found to have
      a large vulvar mass which was initially believed to be a Bartholin duct cyst. At
      surgery a vulvar hematoma was found and evacuated. Subsequent biopsy was negative
      for malignancy. CONCLUSION: Any vulvar mass discovered in a postmenopausal woman
      warrants meticulous evaluation to exclude malignancy. Although usually occurring
      in younger women, a vulvar hematoma may be noted in older women who have
      sustained trauma to the perineum.

PMID- 23550385
TI  - 164 years later, A case report: U. S. Grant, eye pain and swelling in Mexico
      1848.

PMID- 23550386
TI  - When do your rights end and my rights begin?

PMID- 23550387
TI  - "The second rule".

PMID- 23550388
TI  - About group A streptococcal pharyngitis guidelines.

PMID- 23550389
TI  - Dr. William Lattimore's hand-woven frock coat.

PMID- 23550390
TI  - 2013 House of Delegates.

PMID- 23550391
TI  - MRS findings in a patient with juvenile-onset Alexander's leukodystrophy.
AB  - Alexander's leukodystrophy is a rare cerebral white matter disorder with an onset
      that can be infantile, juvenile, or occur in the adult years. It is thought to be
      demyelinative, but the pathogenesis is ill-defined. We report a 24-year-old woman
      with juvenile-onset Alexander disease, of 12 years duration, who underwent
      magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
      serially as part of her care. The patient's latest MRI showed periventricular
      increased signal intensity on T2 and fluid attenuation and inversion recovery
      sequences, which appeared stable when compared to her first study seven years
      ago. MRS revealed an elevated choline/creatine ratio with relative suppression of
      the n-acetyl aspartate peak, also similar to her previous MRS findings. MRS also
      showed elevation of myoinositol levels, best demonstrated with the short echo
      time spectra. These findings support the primarily demyelinative characteristics
      of this leukodystrophy and may provide a surrogate marker of disease progression,
      as well as a potential response to therapeutic intervention when this becomes
      available.

PMID- 23550392
TI  - Preoperative electrocardiogram in an 89-year-old man.

PMID- 23550393
TI  - Acinar cell carcinoma presenting as a duodenal mass: review of the literature and
      a case report.
AB  - Heterotopic pancreatic tissue is not uncommon. Although the cancerous
      transformation of heterotopic pancreatic tissue is a theoretical possibility, it
      is an extremely rare phenomenon. The majority of the heterotopic pancreatic
      malignancies reported in the literature are adenocarcinomas (32 cases). An Acinar
      Cell Carcinoma (ACC) arising from heterotopic pancreatic tissue is even less
      common with only six cases being reported. This report presents an extremely rare
      case of heterotopic pancreatic ACC presenting as a duodenal mass. We propose that
      heterotopic pancreatic ACC should be considered as a possibility in the
      differential diagnosis of a duodenal mass.

PMID- 23550394
TI  - Anaplastic large cell lymphoma in the setting of textured breast implant: a call
      for patients and physicians education.
AB  - An anaplastic large cell lymphoma (ALCL) arising from the breast tissue is an
      extremely rare cancer possibly associated with breast implants. According to the
      FDA database, there are only approximately 60 reported cases of ALCLs in women
      with breast implants worldwide, and there is the possibility that some of those
      are duplicate reports of a single case. Here, we present a case of ALCL in a
      woman who had breast implants for more than 10 years. We discuss preoperative
      imaging and intraoperative findings, along with the histopathology features and
      the postoperative management. We suggest that the possibility of late
      presentation of ALCL be discussed with the patients when we offer and consent
      them for implant reconstructions following breast surgeries. Increased awareness
      of the patients and the physicians would make the diagnosis of this entity less
      of a challenge.

PMID- 23550395
TI  - A case of glioblastoma in infarcted brain.
AB  - Patients with occult cancer of systemic or intracranial origin may clinically
      present with stroke as an initial manifestation due to tumor-associated
      hemorrhage and/or infarction. Such cases are usually clearly temporally related.
      We present a case with separate instances of hemorrhagic infarction and
      subsequent glioblastoma that were temporally separated by several years. This
      case may be an illustration of recent findings in mechanisms of brain repair and
      tumor biology.

PMID- 23550396
TI  - Investigating cancer clusters in Louisiana and interpreting results.
AB  - Physicians are often asked questions related to cancer frequency in their
      communities, particularly in Louisiana because of the perception of high cancer
      rates in this region. When individuals perceive a higher than normal rate of
      cancer in their geographic area, time frame, or group of people, questions about
      the potential role of environmental contamination are often raised. The purpose
      of this article is to educate clinicians about the concept of cancer clusters so
      they can further disseminate this knowledge to patients concerned about increased
      cancer frequency in their communities. This article will accomplish this goal
      through the consideration of potential questions or concerns patients might
      present related to cancer frequency in their communities.

PMID- 23550397
TI  - ECG of the month. Irregular rhythm in a 25-year-old man with three prior cardiac
      operations. Coarse atrial fibrillation with a rapid ventricular response, left
      anterior fascicular block, left ventricular hypertrophy with repolarization
      abnormality.
AB  - The patient underwent closure of an atrial septal defect at age 3, had a leaking
      "mitral" valve repaired at age 9, and at age 13 had a "mitral" valve replacement.
      He began taking warfarin sodium at that time and remained symptom-free until 10
      days before his initial visit here when he presented to another hospital with
      dyspnea and palpitations. Treatment there consisted of lisinopril 10 mg qd,
      carvedilol 6.25 mg bid, aldactone 25 mg qd, furosemide 40 mg qd, digoxin 0.25 mg
      qd, and a continuation of warfarin sodium 7.5 mg qd. An echocardiogram showed a
      left ventricular ejection fraction of 20%. After diuresis, he was referred to our
      cardiology clinic. On his initial visit here, his heart rate was an irregular 120
      beats/min, his blood pressure was 106/77 mmHg, and closing and opening snaps of a
      normally functioning mechanical mitral valvular prosthesis were heard. He was
      obese (height, 5' 9"; weight, 272 lbs). An electrocardiogram was recorded (Figure
      1).

PMID- 23550398
TI  - Radiology case of the month. 32-year-old male with parathyroid carcinoma.

PMID- 23550399
TI  - Clinical case of the month. A 50-year-old man with a persistent rash.
AB  - In September 2006, the United States Centers for Disease Control and Prevention
      (CDC) published updated recommendations for routine opt-out human
      immunodeficiency virus (HIV) testing in all healthcare settings. As late
      diagnosis of infection increases individual and societal risks, a goal of the
      2010 National HIV/AIDS Strategy is to increase the percentage of those aware of
      their infection. In 2008, two years following changes in the CDC testing
      recommendations, 44.6% of individuals 18-64 years of age reported a history of
      having a HIV test, resulting in close to 40,000 new HIV diagnoses. Emergency
      departments accommodate more than 120 million patient visits per year in the
      United States and can be the only point of contact individuals have with the
      healthcare system, particularly in uninsured and marginalized groups. Further
      implementation of opt-out testing can result in earlier diagnosis and improved
      health outcomes at the both the individual and public health levels.

PMID- 23550400
TI  - Idiopathic pulmonary hemosiderosis presenting as a rare cause of iron deficiency
      anemia in a toddler--a diagnostic challenge.

PMID- 23550401
TI  - The importance of evaluation of Celiac disease in patients with pulmonary
      hemosiderosis.

PMID- 23550402
TI  - [The social significance of medical arbitration].
AB  - The physician-patient relationship has been modified with the participation of
      other professionals that work on health services, the family and the community;
      as well as by scientific and technical developmental and the empowering of the
      citizens. The objective of the medical arbitration is to assure the patient
      general rights and to the professional of health. The model utilized for
      arbitration in our country is a reconciliation kind and the mediator quality is a
      warranty for the conciliation, the recommendation or the emission of an opinion
      judgment.

PMID- 23550403
TI  - [Emergent virosis in Mexico].

PMID- 23550404
TI  - [Health profile of Instituto Mexicano del Seguro Social workers].
AB  - OBJECTIVE: To determine the association between risk factors, dietary habits,
      physical activity, alcohol and tobacco consumption, in the presence of obesity,
      hypertension, diabetes mellitus, myocardial infarction, stroke, chronic
      obstructive pulmonary disease, liver cirrhosis, and cancer, in health care
      workers (and other categories of employees) of the Instituto Mexicano del Seguro
      Social (IMSS). METHODS: From March to December 2009, 20,000 surveys were
      conducted among randomly selected workers on 35 IMSS delegations. The variables
      of the study included affiliation, sex, age employment status, registration of
      known diseases, smoking, nicotine addiction, risk drinking, alcohol addiction,
      eating and exercise habits. RESULTS: Workers with poor eating habits, sedentary
      lifestyle smoking and alcohol abuse are more frequently exposed to the presence
      of obesity, hypertension and diabetes mellitus and these in turn to cancer,
      chronic obstructive pulmonary disease, myocardial infarction, cerebral vascular
      disease and liver cirrhosis. CONCLUSIONS: This study shows that IMSS workers have
      a high exposure to risk factors associated with the presence of chronic diseases
      and their complications. It is necessary to enable them to improve significantly
      their health profile.

PMID- 23550405
TI  - [Changes in body composition according to kidney damage in patients with type 2
      diabetes mellitus].
AB  - OBJECTIVE: To know the relationship between total body composition and the stage
      of kidney damage, according to the K/DOQI classification, in patients with type 2
      diabetes mellitus (T2DM). METHODS: Under a correlation design, adults with T2DM
      were studied. Age, evolution time, fat and lean mass, fat percentage, total
      water, body index mass (BMI), creatinine clearance by Cockroft-Gault (CrCCG),
      glucose, HbA1c, proteinuria and microalbuminuria were determined. T test to
      compare independent means and Spearman correlation were used. RESULTS: The study
      included 60 men (23.4%) and 196 women (76.6%). There were no differences by
      gender when comparing age, BMI, duration of T2DM, blood glucose and HbA1c. The
      analysis showed a direct relationship between BMI (r = 0.281), the amount of fat
      mass (r = 0.360), lean tissue (r = 0.158), and water (r = 0.176) with the CrCCG
      (p < 0.0001). The biggest change in body composition, due to fat mass, was
      observed in chronic kidney disease stages 1-3, in which BMI had a good
      correlation with fat mass (r = 0.80, p < 0.001). CONCLUSIONS: Fat mass is
      inversely related to the stage of kidney damage in patients with T2DM.

PMID- 23550406
TI  - [Sensitivity and specificity of a utility model of the detection of diabetic
      neuropathy].
AB  - OBJECTIVE: To determine whether a utility model can be used with acceptable
      sensitivity and specificity for the diagnosis of diabetic peripheral neuropathy
      (DPN). METHODS: Cross sectional study, non-probability sampling, in 381 type 2
      diabetic patients with diabetic foot risk. To determine the DPN, it was evaluated
      the protective sensation in 10 sites on the foot. It was a positive diagnosis if
      three or more points showed insensitivity at the touch of the skin with Semmes
      Weinstein monofilament (SWM). Monofilament was compared to the utility model
      (MMU); the diagnostic methods of application were the same for both. RESULTS:
      Mean age was 62 years, 11 years of development of DM, mean body mass index of 29
      kg/m2, average glucose 129 mg/dL (78-264 mg/dL). With sensitivity of 73.68%,
      97.67% of specificity, positive predictive value 77.78%, negative predictive
      value 97.10%, the positive likelihood ratio was 31.59 and the negative likelihood
      ratio 0.27. CONCLUSION: Currently, diagnostic devices for tactile sensory loss
      are not readily available in our country; therefore, the results of this research
      will help to make the diagnosis of the MMU timely, inexpensive and easily
      accessible.

PMID- 23550407
TI  - Genetic polymorphisms of the tumor necrosis factor and lymphotoxin alpha in type
      2 diabetes.
AB  - OBJECTIVE: To investigate the frequency of the single-base change polymorphic
      variants identified in tumor necrosis factor (TNF) gene (-308 G/A) and
      lymphotoxin alpha (LTA) (+252 G/A) in patients with type 2 diabetes (T2D).
      METHODS: A prospective study in a Mexican-mestizo population of 51 patients with
      T2D and 48 healthy subjects was carried out. We took a peripheral blood sample
      from each individual for identification of the polymorphic genotypes by
      polymerase chain reaction. RESULTS: The genotype distribution in T2D was: TNF
      alpha homozygous 0%; TNFG/A heterozygous 20%; TNFG homozygous 80%. CONCLUSIONS:
      In regards to the TNF -308 G/A genotype, we found a significant difference (p =
      0.012) with a bigger frequency in the group of patients. The health controls
      showed a higher frequency of TNF -308 G/G genotype (p = 0.034).

PMID- 23550408
TI  - [Scleroderma: an update on the pathogenesis and treatment].
AB  - Scleroderma is a multiorganic disease characterized by inflammatory, vascular and
      sclerotic changes in skin and internal organs. It is considered as a tripartite
      disease, associated to autoimmune, fibroblast and endothelial defect, due to
      genetic, environmental and infectious factors. This disease can be classified in
      systemic and localized form. The Raynaud phenomenon occurs in 90% of the patients
      with the diagnosis. It explains the microcirculation involvement and the
      reduction in the number of capillaries. Malformation of nail bed capillaries is
      readily demonstrated by nail bed microscopy and has been shown to correlate both
      with disease severity and with degree of internal organ involvement. The MRSS-51
      validates the skin involvement and has the main predictive value to determine the
      patient survival. MRSS-51 should not be considered as an activity disease
      parameter or used to validate the effectiveness of treatment. Nowadays, multiple
      treatment alternatives exist for scleroderma disease; however these treatments
      offer poor results for the cutaneous manifestations.

PMID- 23550409
TI  - [Perspective on type 2 diabetes mellitus in the Instituto Mexicano del Seguro
      Social].
AB  - The Instituto Mexicano del Seguro Social--always sensitive to the needs of health
      of the beneficiary population and to the demographic and epidemiological changes
      of the society--has developed and implemented DiabetlMSS, a program of attention
      to the diabetic patient. DiabetlMSS organizes care processes based on the needs
      and values of the patients, through simultaneous activities of individual
      consultation and group meetings granted by the multidisciplinary health team.
      These actions and activities are focused to affect patients' lifestyles
      positively. Through a plan of nutrition, physical activity, self-care and
      monitoring, this program increases the interaction between patients, by having an
      exchange of successful experiences about diabetes control. DiabetlMSS was created
      with the purpose that the patients achieve the metabolic control and identify
      complications early on, with the perspective of timely intervention that is
      reflected in the decrease of the catastrophic effects that causes the disease,
      both for patient's life expectancy and the quality of care provided by the
      Institute.

PMID- 23550410
TI  - [Clinical research. XIII. Research design contribution in the structured revision
      of an article].
AB  - The quality of information obtained in accordance to research design is
      integrated to the revision structured in relation to the causality model, used in
      the article "Reduction in the Incidence of Nosocomial Pneumonia Poststroke by
      Using the 'Turn-mob' Program", which corresponds to a clinical trial design.
      Points to identify and analyze are ethical issues in order to safeguard the
      security and respect for patients, randomization that seek to create basal
      homogeneous groups, subjects with the same probability of receiving any of the
      maneuvers in comparison, with the same pre maneuver probability of adherence, and
      which facilitate the blinding of outcome measurement and the distribution between
      groups of subjects with the same probability of leaving the study for reasons
      beyond the maneuvers. Other aspects are the relativity of comparison, the
      blinding of the maneuver, the parallel application of comparative maneuver, early
      stopping, and analysis according to the degree of adherence. The analysis in
      accordance with the design is complementary, since it is done based on the
      architectural model of causality, and the statistical and clinical relevance
      consideration.

PMID- 23550411
TI  - [Effectiveness of the diabetes education program (DiabetIMSS) on clinical and
      biochemical parameters].
AB  - OBJECTIVE: To evaluate the clinical and biochemical parameters, both initial and
      final in patients with type 2 diabetes mellitus, after a year of educational
      intervention. METHODS: We conducted a retrospective, observational, and
      longitudinal study in 126 subjects with type 2 diabetes mellitus from diabetes
      education program (DiabetlMSS). We reviewed the charters of evaluation, and
      recorded clinical data (weight, BMI, waist circumference) and biochemical
      parameters (glucose, cholesterol, triglycerides and glycosylated hemoglobin). The
      information was analyzed by paired Student's t test, and McNemar's test. RESULTS:
      Mean age was 58 years with a female predominance of 70.87%. The paired Student's
      t values reported reduction in weight, BMI, waist circumference, glucose,
      triglycerides and glycosylated hemoglobin (p < 0.001), but showed no difference
      for cholesterol (p > 0.001). Glycemic and metabolic control was not significant
      (p > 0.001) using McNemar's test. CONCLUSIONS: The diabetes education program is
      an essential component of strategies for prevention and successful treatment to
      reduce some clinical and biochemical parameters, but not to reach glycemic and
      metabolic control.

PMID- 23550412
TI  - [Depressive disorder and issues related to DiabetIMSS beneficiaries].
AB  - BACKGROUND: Diabetes mellitus type 2 (DM2) is the leading cause of death in
      people from 15 to 64 years in Mexico, and other regions in the world. For the
      chronic nature of diabetes and complications caused by inadequate metabolic
      control, patients may have mood disorders such as depression. Several studies
      have demonstrated higher prevalence of depression in diabetic patients than in
      general population. Our objective: is to determine prevalence and factors
      associated with depressive disorder in patients with type 2 diabetes mellitus
      enrolled in DiabetIMSS during 2010. METHODS: Analytical study with random
      probability sampling. The analysis included prevalence, odds ratios with 95%
      confidence intervals. The Center Epidemiological Studies Depression Instrument
      was used. RESULTS: Prevalence of depression was 32.7% at 95% CI = 26.4-38.9%),
      67.3% for women, 32.7 % for men; good metabolic control was 51.9%, CI = 95%
      (45.13-58.66%). CONCLUSIONS: We found a higher prevalence of depressive disorders
      than in the general population, no statistical association with glycemic control,
      keeping a greater proportion of women as well as the main aspect of depression
      associated with the perception of emotional support. We discuss DiabetIMSS
      program effectiveness.

PMID- 23550413
TI  - [Bronchial artery embolization with vascular ocluder device in a patient with
      hemoptysis].
AB  - BACKGROUND: Hemoptysis is a sign that can be secondary to various clinical
      entities. Depending on the amount of bleeding, it may even endanger the patient's
      life. The presence of a dilated and tortuous bronchial artery may explain the
      hemoptysis, whose treatment consists in closing the vessel. Our objective is to
      demonstrate the percutaneous closure of a disrupt of the bronchial artery which
      causes hemoptysis. CLINICAL CASE: A 49-years old woman with mild hemoptysis and
      the presence of an abnormal bronchial artery bleeding that underwent percutaneous
      closure device plug. The device was implanted without complications and it was
      not observed passage of dye into the bronchial artery occluded through the
      pigtail catheter angiography control. The patient had no further episodes of
      hemoptysis. CONCLUSIONS: pulmonary arteriovenous malformations can be treated
      successfully by the percutaneous route.

PMID- 23550414
TI  - [Maxillary osteosarcoma. A woman with 12 years of survival].
AB  - BACKGROUND: The osteosarcomas of the jaws are infrequently tumors. The
      accelerated bone growthing and the swelling with nervous sensibility alterations
      are suggestive of malignancy. The diagnosis is established only by the
      histological study and the standard treatment used is surgery with a poor
      survival prognosis of only 25% at five years for those cases with margins free of
      tumor. CLINICAL CASE: A female with an osteosarcoma of the jaw limited to the
      anterior left face of the maxillary and malar area without involve of the
      alveolar bone. A modified maxillectomy wasdone. Chemotherapy and radiotherapy
      were given after surgery. At the present, the patient is free of malignancy
      activity after twelve years of survival. CONCLUSIONS: No matter the systemic
      chemotherapy in maxillar and jaw osteosarcomas is little effective, the early
      diagnosis and treatment was the key in the clinical evolution of the patient
      presented and in who the first elected treatment was surgery.

PMID- 23550415
TI  - [Practice guideline. Diagnosis and treatment of type 2 diabetes mellitus].
AB  - Our objective was to develop a guide based on the best available evidence that
      allow family physicians to establish criteria for screening, diagnosis,
      prevention, treatment of disease, early detection and management of
      complications; to standardize the organizing processes of the diabetic patient's
      care in the primary care level; and to achieve lifestyle modification for
      patients and promote self-care. Clinical questions were stated according to the
      diagram and structured patient-intervention-comparison-outcome. We used a mixed
      methodology-adoption adjustment, and include 32 guides. For recommendations not
      included in these, the search process was conducted in PubMed and Cochrane
      Library Plus with these terms: diabetes mellitus type 2, epidemiology, detection
      and diagnosis, classification, drug therapy, effects, prevention, control and
      complication. The clinical practice guideline emphasizes the fundamental change
      in lifestyle (diet and exercise), self-care and proactive participation of the
      patient, in addition to the dynamic prescription of medications that would
      achieve metabolic control in order to reduce late complications.

PMID- 23550416
TI  - Evaluation of the XIENCE V everolimus eluting coronary stent system in the Asian
      population of the SPIRIT V single arm study. 2-year clinical follow-up data.
AB  - BACKGROUND: Asian patients have a uniquely high risk for heart disease compared
      to other ethnicities. Past drug eluting stent trials have examined mainly
      populations of European heritage. As a significant proportion of the real world
      population in the SPIRIT V single arm study is Asian, the study provides insight
      into how this population responds to stenting with the XIENCE V Everolimus
      Eluting Coronary Stent (EES). METHODS AND RESULTS: 2,700 patients were enrolled
      at 93 sites in Europe, Asia Pacific and Canada between November 2006 and November
      2007. 698 (26%) patients were recruited from Asian sites in India, China, Hong
      Kong, Malaysia, Singapore and Thailand. De novo coronary artery lesions of all
      patients were to be treated with up to 4 planned EES. Up to 2 year follow-up,
      major adverse cardiac events, myocardial infarction and target lesion
      revascularization rates were lower in the Asian subgroup than in the non-Asian
      subgroup. These results were mainly driven by better clinical outcomes in the
      Indian population. All populations showed similar low stent thrombosis rates.
      CONCLUSION: These findings demonstrate the safety and efficacy of the EES when
      used in a real-world Asian population, known to be at higher risk for heart
      disease.

PMID- 23550417
TI  - A study of platelet aggregation in patients with acute myocardial infarction at
      presentation and after 48 hrs of initiating standard anti platelet therapy.
AB  - AIMS & OBJECTIVES: Platelet aggregation is a key factor behind coronary artery
      disease. Various complications after an attack of acute coronary syndrome are
      often related to the platelet hyperactivity in the early hours following the
      event. There is a growing concern regarding aspirin & clopidogrel resistance,
      which has put the time-tested therapies under scrutiny. Time has come to address
      the issue of platelet hyperactivity in the early hours & whether to individualize
      therapy and drug doses in different patients. MATERIALS & METHODS: We
      prospectively enrolled 41 patients with a diagnosis of acute myocardial
      infarction (AMI) between July 2009 and July 2010 admitted to the cardiology ward
      and ICCU of Medical College, Kolkata, after fulfillment of inclusion & exclusion
      criteria. The study was reviewed and approved by the Institutional Ethical
      Committee. Platelet Aggregation (PA) with 10 microM epinephrine, 2 microg/ml
      collagen and 10 microM ADP was performed with light transmittance aggregometry in
      all patients according to the standard protocol. Tests were done within 3 hours
      of sampling with platelet-rich plasma (PRP) by the turbidometric method in a 2
      channel aggregometer (Chrono-Log 490 Model, Chrono-Log Corp, Havertown, Pa).
      Aspirin & clopidogrel resistance were defined as per ACC/AHA guidelines. Platelet
      aggregation studies were done at presentation (zero hour) and 48 hours after
      instituting dual antiplatelet therapy in standard doses. RESULTS: Patients with
      first attack of AMI showed a high mean platelet aggregation at 0 hours of 77.4%
      +/- 18.8% with ADP, 77.5% +/- 26% with Epinephrine & 73.5% +/- 24.9% with
      Collagen. With all three agonists, the initial hyperactivity of platelets at 0
      hours was significantly higher among diabetics & obese. Though reduced,
      significant platelet hyperactivity remained at 48 hours after initiating standard
      antiplatelet therapy; 50.3% +/- 14.3% with ADP, 56.5% +/- 21.6% with epinephrine
      & 38.4% +/- 22% with collagen. CONCLUSION: In the early hours after AMI there is
      a fairly high degree of platelet aggregation. Even after 48 hours of standard
      antiplatelet therapy the platelet aggregation though reduced, still remains
      significantly high. Since recurrent ischemic episodes frequently occur in this
      vulnerable period, time has come to assess platelet aggregation status in high
      risk groups, if not in all patients of acute coronary syndrome during this period
      so that therapy may be individualized. Further researches are required in this
      area.

PMID- 23550418
TI  - Impact of angiographic & procedural factors on the treatment of ostial LAD or
      LC(x) disease.
AB  - AIMS & OBJECTIVES: This study was designed to evaluate the impact of angiographic
      & procedural factors on MACE after DES deployment in ostial lesions of LAD &
      LC(x). PATIENTS, MATERIALS & METHODS: 65 patients with ostial disease of LAD or
      LC(x) underwent PCI using DES. In 56 patients the stent was placed perfectly at
      the ostium & in 9 patients the LMCA was covered as per protocol. Angiographically
      48 patients had a bifurcation angle > 70 degrees whereas in 17 patients the angle
      was < 70 degrees. RESULT & ANALYSIS: Multivariate Regression Analysis was done.
      Mean age was 59 years & 77% were male patients. 69% were hypertensives & 52%
      diabetics. LAD was treated in 88%. 74% had bifurcation angle > 70 degrees. 26%
      presented with an angle < 70 degrees LMCA was covered during stent implantation
      in 12% of cases. Average follow up was 1.5 +/- 0.8 years. Overall MACE was 12%.
      Bifurcation angle > 70 degrees & use of Cypher stent remained significant in
      reduction of MACE (P < 0.05). Using Univariate analysis of 2 sample sets like
      cases with angle of separation > 70 degrees (n = 48) & with angle less than < 70
      degrees (n = 17), it was found that covering LMCA was beneficial in cases with
      angle of separation < 70 degres (p-value and correlation coefficient nearer to
      statistical significance). CONCLUSION: Angiographic factors like bifurcation
      angle is important to formulate the strategy of stenting procedure in the ostial
      disease of LAD or LC(x) even with DES.

PMID- 23550419
TI  - Study of cardiovascular risk factors among tertiary hospital employees and their
      families.
AB  - BACKGROUND: Cardiovascular diseases have become the leading cause of mortality
      and morbidity in most countries of the world. The aim of the present study was to
      estimate the prevalence of cardiovascular risk factors among administrative
      employees working at a tertiary hospital (All India Institute of Medical
      Sciences, New Delhi) and their families. METHODS AND RESULTS: A cross-sectional
      survey was conducted among a total of 453 individuals aged 30 years and above (N1
      = 453 for the questionnaire, anthropometric and clinical parameters; N2 = 429 for
      biochemical investigations). Evaluation for cardiovascular risk factors,
      anthropometric measurements, blood pressure, fasting blood glucose and serum
      lipids were performed using standard definitions. The mean age of the study group
      was 43.3 +/- 9.5 years. There was a high prevalence of major cardiovascular risk
      factors--current smoking in 58 (12.8%), tobacco consumption in 26 (5.7%), family
      history of coronary artery disease 79 (17.4%), diabetes mellitus in 25 (5.8%),
      hypertension in 94 (20.7%), hyperlipidemia--hypercholesterolemia in 110 (25.7%) &
      hypertriglyceridemia in 148 (34.5%), physical inactivity in 180 (39.7%), body
      mass index e" 23 kg/m2 in 350 (77.3%), central obesity i.e. waist circumference >
      90 cm for males and > 80 cm for females -in 201 (80.1%) of males and 163 (80.7%)
      of females, inadequate fruit and vegetable consumption in 387 (85.4%), heavy
      drinking in 12 (2.6%), and stress in 58 (12.7%). CONCLUSION: The study
      demonstrated an overall high prevalence of cardiovascular risk factors even
      amongst employees at a tertiary hospital and their families. This indicates an
      urgent need to initiate a comprehensive health promotion and cardiovascular
      disease prevention programme at workplace and community level.

PMID- 23550420
TI  - Coronary artery bypass grafting in women--is OPCAB mandatory?
AB  - OBJECTIVE: There has been an explosive increase in our understanding of the
      natural history and progression of CAD in women. Women have a poorer prognosis
      and a more severe outcome than men after myocardial infarction, Percutaneous
      transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting
      (CABG). The purpose of the present study was to evaluate the differences in the
      results of CABG in women as compared with men using Pump and Off Pump operating
      techniques. METHODS: Data of 3500 patients undergoing coronary artery bypass
      grafting by a single surgeon at two institutes over an 8-year period were
      analyzed. Clinical data including demographic and risk profile and perioperative
      data were obtained from case records, operation notes, ICU charts and out-patient
      records. Data were analyzed using 'chi square' test to calculate p value for
      various parameters. RESULTS: 14.6% of patients were women. Coronary artery size
      correlated with body surface area (BSA) but even with BSA > 1.5m2, it was smaller
      than the males. Inhospital mortality was higher in women as compared to men,
      being 2.92% versus 1.8% in men. The ventilation time, blood requirement, ICU
      stay, inotropic requirement and hospital stay were identical with results seen in
      men in our series. The commonest causes of mortality were low cardiac output and
      renal failure. Use of Off Pump technique reduces mortality (1.84% Vs 4.5% on Pump
      -p = 0.01) in women, besides reducing the blood requirement (2.5 +/- 1.2 units/pt
      in OPCAB Vs 4.3 +/- 1.4 units/pt in Pump group--p < 0.001; ICU stay (29.4 +/-
      16.4 hrs Vs 38.3 +/- 17.3 hrs in Pump group--p < 0.0001); & hospital stay (6.81
      +/- 1.6 days Vs 8.05 +/- 2.1 days in pump group--p < 0.0001). However, there was
      no statistically significant difference in the rates of mediastinitis,
      Arrhythmias, Neurological or Pulmonary complications between the OPCAB & Pump
      group. CONCLUSIONS: Women coming for coronary artery bypass surgery are a special
      risk group. The operative and early mortality of bypass surgery in women is
      higher than in men for conventional CABG. However, off pump techniques has
      negated this to a large extent. Our findings lead us to conclude that use of
      OPCAB promises to be gratifying enough to mitigate the early concerns in this
      group of patients.

PMID- 23550421
TI  - Left ventricular chamber quantification by real time 3D echocardiography.
AB  - Accurate assessment of left ventricular (LV) function, LV volume, ejection
      fraction and segmental wall motion abnormalities is essential for clinical
      decision-making and follow-up assessment. Currently, two-dimensional
      echocardiography is the most widely used method to obtain this information. Three
      dimensional echocardiography has shown to be an accurate and reproducible method
      for LV quantitation. In this review, we describe various methods to acquire a 3D
      dataset for LV volume and wall motion analysis, including their advantages and
      limitations. We provide an overview of studies comparing LV volume and function
      measurement by various gated and realtime 3D echocardiography methods of
      acquisition compared to magnetic resonance imaging. New technical advances like
      online assessment and single beat acquisition of data have minimized the errors
      in assessment of LV function.

PMID- 23550422
TI  - Lipid modifying action of atorvastatin in comparison to combination of
      atorvastatin and nicotinic acid in patients with ischaemic heart disease.
AB  - AIMS AND OBJECTIVES: The current study is a prospective, randomized controlled
      study with two parallel treatment groups done to assess the tolerability and
      efficacy of a combination of atorvastatin (10 mg) and extended release nicotinic
      acid (1G) in comparison to atorvastatin (20 mg) alone in modulating the lipid
      profile in patients of Ischemic Heart Disease in our population. METHODS AND
      RESULTS: Patients were randomly allocated into two equal groups (n = 216) as per
      selection criteria. Group A received Atorvastatin 20 mg while Group B received
      combination of Atorvastatin -10 mg and extended release nicotinic acid (1G), both
      once daily at bed time, for a period of 24 weeks. Final end-of-study assessment
      and evaluation of tolerability and efficacy was done after 24 weeks. Comparison
      between the groups was performed with paired t-test. A p value < 0.05 was
      considered to be statistically significant. There was significant reduction in
      cholesterol, LDL & triglycerides in both the groups. Mean values of cholesterol
      and LDL were comparable in both groups where as there was increased reduction of
      triglycerides in Group B. Mean value of HDL cholesterol significantly increased
      only in group B thus the total cholesterol: HDL ratio was decreased more
      favorably. SGPT level was not significantly altered in either of the groups.
      CONCLUSION: In the Indian perspective, where HDL is low and the LDL values are
      not very high, a combination of low dose atorvastatin with nicotinic acid may
      influence the lipid profile more favorably and reduce the cholesterol/HDL ratio
      in comparison to atorvastatin alone and is also fairly well tolerated.

PMID- 23550423
TI  - Enhanced external counterpulsation and CVD protection: 3D echo validation: a
      promising approach.
AB  - AIMS & OBJECTIVE: To evaluate the impact of enhanced external counterpulsation
      (EECP) on various echo variables by 3D-Echocardiography. MATERIALS AND METHODS:
      60 adult patients from indoor and outdoor patient department; consisting of 16
      patients with heart failure (HF) with left ventricular systolic dysfunction, 20
      patients with heart failure with normal ejection fraction (HFNEF), 4 patients
      with prior percutaneous coronary intervention (PCI), 3 patients with prior
      coronary artery bypass grafting (CABG) and 17 patients with syndrome X; were
      subjected to Echocardiographic evaluation. The various echo variables included
      were left ventricular myocardial performance index (LVMPI), left ventricular mass
      index (LVMi), left ventricular diastolic dysfunction (LVDD), left ventricular
      systolic function (LVEF) and left atrial volume index (LAVi). Once randomized,
      patients underwent 35 hrs EECP treatment sessions, each lasting 1 hour, could be
      given once or twice per day. RESULTS: There was a significant reduction in the
      overall prolonged mean LVMPI from baseline (0.54 +/- 0.2) to post ECP treatment
      (0.43 +/- 0.1) in the total study population (p < 0.001). EECP treatment
      significantly reduced baseline grade II or grade III diastolic dysfunction and
      E/E' ratio > 12, but not in patients with baseline E/E' < 12, baseline normal
      diastolic function or grade I diastolic dysfunction. Similiarly the mean LVEF in
      the subset of patients with HF treatment was 30.7 +/- 3.1; post ECP the mean LVEF
      was increased to 36.9 +/- 3.2 which was statistically significant (p < 0.001). In
      the remaining patients, who had mean LVEF within normal range, there was no
      significant difference pre and post EECP (p value- NS). Pre EECP the mean LAVi in
      the total population was increased up to 33.4 +/- 5.6 ml/m2. Post EECP the mean
      LAVi reduced to 24.8 +/- 4.2 ml/m2, which was also statistically significant (p <
      0.001). Regarding mean LVMi as well as in the patterns of LVH, there were no
      significant changes seen as compared to baseline. CONCLUSION: Enhanced External
      counterpulsation is noninvasive, non-surgical method of choice for CVD & heart
      failure protection. It is very useful in Single vessel or multivessel disease,
      heart failure, HFNEF, Post PCI or post CABG and syndrome X. It reduces LVMPI and
      improves global cardiac function, increases LVEF in patients with ejection
      fraction of less than 50%, reduces grade II or grade III diastolic dysfunction
      and E/E' ratio more than 12, decreases LAVi by 25.7%; thereby reducing adverse
      clinical events in CAD and heart failure.

PMID- 23550424
TI  - Does rheumatic valvular heart disease affect right ventricular performance?
AB  - AIM: Right ventricular (RV) function often determines clinical outcome in
      patients with valvular heart disease. Though difficult to assess by
      echocardiography, Tei index is useful in its assessment. The aims of the study
      were to evaluate global RV function using the Tei index in patients with
      rheumatic heart disease and to observe if such abnormalities in RV function were
      reversible post-operatively. METHOD: The study included patients with atrial
      septal defect (ASD, Group I, n = 15) and rheumatic valvular heart disease (RVHD,
      Group II, n = 18). Patients with atrial fibrillation were excluded from the
      study. Conventional 2-D echocardiography was performed preoperatively, immediate
      postoperative and in last follow-up. RESULT: ASD group had lower left LVES and
      LVED dimensions as compared to RHVD (p = 0.001) and better ejection fraction (EF)
      than RVHD group (p = 0.02). LV Tei in the ASD group was above the normal limit (>
      0.5), while RV Tei was increased in the RHVD group. The median RVSP was similar
      in two groups (p = 0.9). The impaired LVMPI in the ASD group improved as early as
      2 weeks following surgery (p = 0.09) while in patients with RHVD it deteriorated
      which mirrored the reduction in median LVEF (p = 0.04). Group II that had an
      abnormal RV Tei pre-operatively demonstrated improvement following surgery (p =
      0.03). CONCLUSION: RVHD is associated with impairment of RV function. Volume
      overload of RV in patients of ASD is associated with normal MPI. The
      abnormalities in RVMPI improved as early as 2 weeks after valve surgery with
      sustained improvement noted at follow up.

PMID- 23550425
TI  - Lipoprotein (a)--lipid profile and apolipoprotein B in children of young parents
      with coronary artery disease.
AB  - OBJECTIVE: To evaluate lipoprotein(a), apolipoprotein B and lipid profile in
      children of young parents with coronary artery disease. DESIGN: Analytical
      observational study. SETTING: Tertiary care hospital. MATERIAL: The study
      included 80 children (9-18 years) out of which 40 were children of young parents
      (one or both) with established coronary artery disease (CAD), while the other 40
      were children of parents with no evidence of CAD (controls). All were evaluated
      for fasting blood glucose, lipid profile, apolipoprotein B and lipoprotein (a) -
      Lp(a). Two sample 't' test was applied for analysis of continuous variables
      between study & control group. RESULTS: The study group children had
      significantly higher levels of total serum cholesterol (p = 0.004), LDL
      cholesterol (p = 0.002), lipoprotein a (p = 0.001) as compared to children of the
      control group. A significant difference in apolipoprotein B levels (p = 0.044)
      was observed in children in the adolescent age group (14-18 years). Both systolic
      and diastolic blood pressures were significantly higher without any significant
      difference being observed for weight and body mass index between the two groups.
      CONCLUSION: Higher levels of pro-atherogenic factors in children with family
      history of premature CAD indicate that the combined effects of "nature and
      nurture" are responsible for development of accelerated atherosclerosis
      especially in Indians. Tracking of Lp(a) levels from childhood may be a better
      option than detecting other elements of dyslipidemia which are not fully
      expressed until middle age.

PMID- 23550426
TI  - In search for novel biomarkers of acute coronary syndrome.
AB  - Prerequisites for a biomarker to enter clinical routine in acute coronary
      syndrome (ACS) are several folds. The most important features are that the
      biomarker can be offered on a routine platform to diagnose and identify high-risk
      individuals of ACS, provide higher sensitivity and specificity than the ECG in
      predicting outcome, and should have impact on therapeutic decision making. In
      recent years, a deeper understanding of the pathobiology of the atherothrombosis
      as the underlying mechanism of ACS has directed scientific studies towards the
      evaluation of certain pathogenic components involved in the process as potential
      biomarkers for the clinical settings of ACS. Under investigations are markers to
      identify early injury/ischemia, markers for detection of vulnerable plaque, its
      disruption, of thrombosis and markers for inflammation. The aim of this paper is
      to review the current contribution of biochemical markers to clinical cardiology
      and also to discuss some important developments in this field.

PMID- 23550427
TI  - Regression of coronary atherosclerosis through healthy lifestyle in coronary
      artery disease patients--Mount Abu Open Heart Trial.
AB  - AIMS: To evaluate the efficacy of a unique healthy and happy lifestyle (HLS)
      program in regression of coronary atherosclerosis and reduction in cardiac events
      in an open trial. METHODS: One hundred and twenty three angiographically
      documented moderate to severe coronary artery disease (CAD) patients were
      administered HLS comprising of low-fat, high-fiber vegetarian diet, moderate
      aerobic exercise and stress-management through Rajyoga meditation. Its most
      salient feature was training in self-responsibility (heal+thy) and self
      empowerment through inner-self consciousness (swasth; swa=innerself,
      sth=consciousness) approach using Rajyoga meditation. Following a seven day in
      house sojourn, patients were invited for six month follow-up for reassessment and
      advanced training. At the end of two years, all patients were asked to undergo
      repeat angiography. RESULTS: Three hundred and sixty coronary lesions were
      analysed by two independent angiographers. In CAD patients with most adherence,
      percent diameter stenosis regressed by 18.23 +/- 12.04 absolute percentage
      points. 91% patients showed a trend towards regression and 51.4% lesions
      regressed by more than 10 absolute percentage points. The cardiac events in
      coronary artery disease patients were: 11 in most adherence, and 38 in least
      adherence over a follow-up period of 6.48 yrs. (risk ratio; most vs least
      adherence: 4.32; 95% CI: 1.69-11.705; P < 0.002). CONCLUSION: Overall healthy
      changes in cardiovascular, metabolic and psychological parameters, decline in
      absolute percent diameter coronary stenosis and cardiac events in patients of CAD
      were closely related to HLS adherence. However, more than 50% adherence is
      essential to achieve a significant change.

PMID- 23550428
TI  - Off-pump trans-apical trans-catheteraortic valve implantation: first successful
      case report in India.
AB  - Trans-catheter aortic valve implantation has emerged as an alternative to
      conventional aortic valve replacement for patients with symptomatic severe aortic
      stenosis considered to be at very high or prohibitive operative risk. We report
      the first successful Off-pump trans-apical trans-catheter aortic valve
      implantation in India for a case of severe calcific aortic stenosis with a
      Logistic Euroscore of 20%.

PMID- 23550429
TI  - The benefits of exercise based cardiac rehabilitation in congestive heart failure
      -a case series.
AB  - Cardiac rehabilitation (CR) for congestive heart failure (CHF) has become the
      main source of interest among cardiologists and rehabilitation specialists. The
      aims of the study were to assess the effects of supervised cardiac rehabilitation
      and a structured home based program on functional capacity and QoL in patients
      with CHF for which ten patients with CHF having NYHA class II-IV were
      rehabilitated using an individualized 9 week, supervised, progressive exercise
      based phase-1 and 2 cardiac rehabilitation program. Patients were discharged on
      an average within 5-7 days and an 8-week home based phase-2 program was given.
      Patients were followed up telephonically every week during which adherence and
      progression of exercises were monitored. The medical outcomes survey short form
      (SF-36), Minnesota living with heart failure questionnaire (MLHFQ), the six
      minute walk test (6MWT), time taken for heart rate recovery (HRR) and RPE post
      6MWT were assessed at discharge and 8 weeks follow up. A pre-post analysis showed
      a significant difference in the SF-36, MLHFQ and 6MWT distance (p < 0.05). These
      findings suggest that early exercise based CR and a home based program improve
      QoL and 6MWT distance in patients with CHF.

PMID- 23550430
TI  - Intra-cavitary course of right coronary artery: what the cardiologists should be
      aware of!
AB  - We report an unusual case of an anomalous intra-cavitary course of the right
      coronary artery (RCA) that was detected on multislice computed tomography (CT)
      angiography. Albeit rare, this anomaly is being picked up with increasing
      frequency owing to the widespread use of coronary CT angiography (CCTA). Although
      this entity does not produce symptoms per se, it can result in potentially
      catastrophic complications during interventional procedures or bypass surgeries
      if not recognized in time.

PMID- 23550431
TI  - Diagnosis of a thrombosed bileaflet prosthetic mitral valve by real-time three
      dimensional transesophageal echocardiography.
AB  - Mitral valve replacement, hence thrombosis of prosthetic heart valves (PHV) are
      not uncommon in our country. The diagnosis is commonly established by increased
      gradients across PHV during transthoracic echo and restricted leaflet movement
      during transesophageal echo or fluoroscopy. We demonstrated the leaflets of a
      bileaflet PHV, of which one was stuck in closed position and the movement of the
      other was partially restricted by real-time three-dimensional transesophageal
      echocardiography.

PMID- 23550432
TI  - Dangerous double density.

PMID- 23550433
TI  - AML abscess or perforation?--A diagnostic dilemma.

PMID- 23550434
TI  - Y-stenting in primary angioplasty of unprotected left main coronary artery.
AB  - Patient presenting with acute lateral wall myocardial infarction was taken up for
      primary angioplasty. Angiogram revealed a totally occluded left main coronary
      artery. Thrombosuction revealed a trifurcation with disease at proximal part of
      all 3 branches. Y-stenting with kissing balloon technique was performed to open
      anterior descending and ramus branches. Patient was free of angina till 6 months
      of follow-up. Kissing balloon technique in primary angioplasty of left main
      artery is reported uncommonly.

PMID- 23550435
TI  - Idiopathic left ventricular hypertrophy in an infant.
AB  - Cardiac hypertrophy in infancy has been a subject of considerable interest. We
      present a case of significant left ventricular hypertrophy without any associated
      cause, presenting in infancy.

PMID- 23550436
TI  - Primary PCI in a patient of inferior ST-segment elevation myocardial infarction
      in the time of severe hyperkalemia: a case report.
AB  - This case report describes the management of a middle-aged hypertensive male
      patient who presented with acute inferior ST-segment elevation myocardial
      infarction accompanied with severe hyperkalemia. His coronary angiography
      revealed a thread like right coronary artery along its entire course and normal
      left coronary artery system with patent coronary stents in the left anterior
      descending and left circumflex arteries. Subsequent to correction of hyperkalemia
      with intravenous calcium gluconate and regular insulin the patient underwent
      primary percutaneous coronary intervention (PPCI) of the right coronary artery
      with the deployment of a sirolimus eluting stent. The patient received overnight
      an infusion of tirofiban at half the usual dose between the diagnostic coronary
      angiogram and PPCI.

PMID- 23550437
TI  - World Aids Day 2012: are you missing the signs of an HIV infection?

PMID- 23550438
TI  - Smoking cessation: promoting the health of older people who smoke.
AB  - Community nurses are well placed to address smoking behaviour with older people.
      Smoking cessation can significantly improve the health and wellbeing of older
      people, and to withhold support for smoking cessation is a form of age
      discrimination. This paper provides advice to community nurses about how to
      approach discussions about smoking behaviour with older clients as part of their
      health education practice. It addresses some of the ethical concerns that have
      been raised by community nurses, explains how smoking in older people may be
      reduced using a harm reduction apporoach and through working with the concept of
      the smoke-free home.

PMID- 23550439
TI  - Researching palliative care: more than patient recruitment and data collection.

PMID- 23550440
TI  - Extending an approach to hospital malnutrition to community care.
AB  - This feature investigates the potential relevance to community care of a new food
      provision and nutritional management system for older hospital patients. A
      qualitative study identified the core factors contributing to inadequate food
      intake in older patients in hospital, including: poor mealtime ambience; lack of
      necessary mealtime assistance; inflexible meal provision; lack of monitoring of
      nutrient intake and absence of accountability in nutritional care. Many of these
      factors are also relevant to older people living in the community. To address
      these issues, we designed a new system for the nutritional care of the older
      patient: 'hospitalfoodie'. Hospitalfoodie facilitates: patient nutritional
      screening; patient-tailored food choice; and information exchange among the
      healthcare team. The system introduces a more flexible approach to provision of
      food, including the development of nutrient-dense 'mini meals' for older
      patients. The system facilitates monitoring of patient food intake against their
      nutrition targets and alerts staff of nutrition shortfalls. The relevance of
      components of hospitalfoodie to community nutritional care was explored through
      qualitative interviews and focus groups with a range of care providers.

PMID- 23550441
TI  - Preparing nursing students to be community health practitioners.
AB  - There is currently a greater emphasis on community-based health care and, with
      that, a shift in focus for pre-registration nursing education within policy
      documents and standards (Nursing and Midwifery Council (NMC), 2010). This paper
      reports a mixed methods study that examined the implementation of an initiative
      that enabled third year adult field student nurses the opportunity to spend the
      final year of their education within the community setting. Using a questionnaire
      and focus groups, the views of students at the end of the 12-month period were
      captured. The diverse approach to the placement provision enabled undergraduate
      nurses to be fit for purpose and ensured that practice at the point of
      registration would meet the challenges of working in the community setting.
      Students developed confidence through the diverse placement provision,
      opportunities for lone working and the support provided by mentors. This model of
      placement provision is worthy of consideration by service leads and curriculum
      planners, particularly in view of the present focus of the NMC's (2010) standards
      for pre-registration nursing programmes.

PMID- 23550442
TI  - Living with heart failure without realising: a qualitative patient study.
AB  - Heart failure is an important problem in Swedish primary healthcare as in the
      U.K. In spite of that little is known about how people with heart failure
      experience support from primary healthcare. This paper investigates how people
      with heartfailure experience support in primary healthcare. Semi structured
      interviews were conducted with five men and five women, born 1922-1951. The
      interviews were analyzed with qualitative content analysis in accordance with
      Graneheim and Lundman (2004). The participants experienced they had not received
      information about their diagnosis or about the cause of their condition. They had
      not been informed they had heart failure. Instead the participants believed their
      symptoms were caused by age, thus being part of normal ageing. They did not
      experience they needed care or support to cope with illness or disease. Instead
      their main needs for support in daily life concerned help with practical
      matters.There is a risk primary healthcare abandons people with heart failure
      meaning the patients are forced to develop strategies on their own in order to
      manage symptoms. When inadequately informed there is also a risk they make up
      their own explanations signifying possible difficulties to handle their health
      situation.

PMID- 23550443
TI  - Deprivation of liberty: the Mental Health Act or the Mental Capacity Act?
AB  - Both the Mental Health Act (1983) and the Mental Capacity Act 2005 now have
      provisions that authorise the care and treatment of a person in circumstances
      that amount to a deprivation of liberty. In accordance with the requirements of
      article 5 of the European Convention on Human Rights both regimes require a
      person to be suffering from a mental disorder before they can be subject to a
      deprivation of liberty. This article rebuts the assumption that practitioners can
      pick and choose which method to use when authorising a deprivation of liberty. It
      goes on to highlight the primacy of the Mental Health Act (1983) when a
      deprivation of liberty is necessary to treat a mental disorder in hospital or
      care home.

PMID- 23550444
TI  - Expert patients programme launches social media resource for patients.

PMID- 23550445
TI  - What should we eat?

PMID- 23550446
TI  - [Histology and molecular biology of GIST].
AB  - Gastrointestinal stromal tumors (GIST) are the most frequent sarcomas but were
      underdiagnosed until the beginning of this century. GIST derive from interstitial
      cells of Cajal and may develop all along the digestive tract. GIST are
      characterized by the expression of KIT (CD117), and also DOG-1, which was
      recently discovered by transcriptome analysis. Gain-of-function mutations of the
      tyrosine kinase receptors KIT and PDGFRA are present in 85% of cases. More than
      150 different mutations have been reported, mostly located in exon 11 of the KIT
      gene. Detection of these mutations may be useful to confirm the diagnosis and to
      evaluate the prognosis. Mutations also have predictive value. For example,
      patients with metastatic GIST and a duplication of KIT exon 9 should receive
      twice the usual dose of imatinib, while GIST with the PDGFRA p. D842 V mutation
      are resistant to imatinib. This article presents the main pathologic
      characteristics of GIST and the important insights that GIST research has
      provided for oncology in general.

PMID- 23550447
TI  - [Gastrointestinal stromal tumors: clinical features and diagnosis].
AB  - Gastrointestinal stromal tumors (GIST) are rare, usually sporadic, and mainly
      located in the stomach or small bowel. Gastrointestinal bleeding is the main
      presenting symptom. GIST are discovered incidentally in 20% of cases. Endoscopy,
      and endosonography when possible, are the diagnostic procedures of choice for
      small GIST, while CT is used for larger tumors. Pathologic diagnosis can be
      obtained by fine-needle aspiration, but its indications must be discussed on an
      individual basis.

PMID- 23550448
TI  - [New surgical approaches to localized and advanced gastrointestinal stromal
      tumors (GIST)].
AB  - Complete resection without tumor rupture remains the mainstay of treatment for
      patients with localized, resectable GIST The surgical indications should take
      into account the size and location of the tumor, both of which influence the risk
      of recurrence. More micro-GISTs are being discovered with more frequent
      investigations, raising the question of a wait-and-see policy for some patients.
      Imatinib is the standard treatment for patients with locally advanced inoperable
      and metastatic tumors. Secondary excision of residual disease has been linked to
      a better prognosis in patients who respond to imatinib, but it is unclear whether
      this is due to the surgery itself or to a selection bias. The EORTC trial,
      designed to resolve this issue, was closed because of low accrual.

PMID- 23550449
TI  - [Medical therapy of GIST; from palliative to curative treatment].
AB  - Since the discovery of the remarkable efficacy of Imatinib in metastatic GIST at
      the end of the last century, dozens of studies have further advanced the
      management of this disease. Considerable progress has been made in the last dozen
      years thanks to this tyrosine kinase inhibitor, not only in terms of the
      definition and classification of these tumors, but also in our knowledge of their
      molecular mechanisms and in the therapeutic management of patients with this rare
      disease. Treatment of GIST now serves as a model--or even the model--for targeted
      therapy in oncology. Over 90% of relapsing patients benefit from first-line
      Imatinib therapy, with a median survival time of 60 months compared to only 18
      months before the Imatinib era. This revolution has transformed the outlook of
      patients with metastatic disease. It has also led to a review of medical and
      surgical attitudes and prolonged the management of these patients, most of whom
      will live normally with dormant residual disease. Imatinib should not be
      interrupted but continued until the tumor progresses or intolerable adverse
      effects occur. Early studies showed that adjuvant Imatinib therapy given for one
      year after resection of localized GIST reduced the recurrence rate by 70% in
      patients with a significant risk of relapse. Administered for three consecutive
      years, Imatinib even had a significant impact on survival. Despite these results,
      the optimal duration of Imatinib therapy in the adjuvant setting remains to be
      defined, as patients who relapse after Imatinib discontinuation remain remarkably
      sensitive to the same drug In addition to Imatinib (and sunitinib, that has also
      proven effective in metastatic disease), several other tyrosine kinase inhibitors
      are in the pipeline. Coupling of these drugs with the GIST molecular profile
      opens up promising perspectives for the future. Successive advances in GIST
      therapy have created significant opportunities for the treatment of other tumors.

PMID- 23550450
TI  - [Pre-hospital management of adults with life-threatening emergencies].
AB  - In France, acute life-threatening situations are handled by the French Secours a
      Personne (assistance to persons) and emergency medical facilities. An unequivocal
      success, this early management of life-threatening emergency situations relies
      upon centralized call reception, medical dispatching, and immediate on-site
      emergency medical care. We describe the different emergency care providers and
      steps involved in the response to emergency situations. Each call centre (Samu,
      phone number 15; Sapeurs-Pompiers, 18) provides a response tailored to the nature
      of incoming calls for assistance. A check-list of grounds for an "automatic
      response" by the SDIS (Service Departemental d'Incendie et de Secours--the French
      fire brigade) is in use, ensuring that firefighters are often the first on the
      spot, while the knowledge and skills of the dispatching physician are essential
      to ascertain the patient's needs, to preserve life and vital functions, and to
      ensure the patient is sent to the appropriate emergency healthcare facility. In
      life-threatening emergency situations, patients must be brought straight to the
      appropriate reference emergency healthcare facility, as quickly as possible,
      without prior admittance to an emergency department. This is the procedure for
      extremely acute emergency situations in the following areas: trauma (multiple
      trauma and/or uncontrolled bleeding, spinal cord trauma), delivery bleeding,
      other life-threatening situations such as ischemic heart disease, cardiac arrest
      (sudden death), cerebrovascular stroke and ensuing brain damage, some acute
      respiratory situations such as anaphylactic shock, foreign-body inhalation,
      electrocution, drowning, drug overdose, certain forms of poisoning, and
      conditions requiring initial hyperbaric oxygen (diving accidents, acute carbon
      monoxide and smoke poisoning). The reasons for suboptimal emergency care in life
      threatening situations are currently a major issue, with medical facilities being
      reduced in some areas, fewer voluntary firemen, hospital reorganization, tight
      funding, difficulties of medical dispatching, and the varying skills of "first-on
      the-scene "emergency workers. Grievances include late emergency responses,
      inappropriate medical care, and dispatching to the wrong facility. This raises
      the question of equal opportunity for all in a country with widely varying
      geographic features and population density. Improvement in the system's
      efficiency will require a series of objectives to be met in varied and
      complementary--Enhanced functional coordination, by speeding up the deployment of
      the ANTARES digital radio-frequency transmission network (Adaptation Nationale
      des Transmissions Aux Risques Et aux Secours).--Implementation of a network of
      emergency services with varying degrees of emergency healthcare management
      related to the technical nature of the facilities. Three levels of emergency
      healthcare must be made available: level 1 is provided by local hospitals, level
      2 includes support facilities available in general hospitals (not necessarily the
      nearest hospital), and level 3 provides specialized healthcare in large and/or
      training hospitals with specialized departments. Life-threatening emergency
      situations are to be handled by level 2 or 3 facilities. Specific facilities must
      be selected as reference centers. In France, the ARS (Agences Regionales de
      Sante) is in charge of this procedure, as it provide funding for healthcare
      continuity--Reducing inequalities in access to emergency care. This will involve
      improving the network of SDIS brigades, making local medical facilities more
      responsive, delegating more medical procedures, on-site telemedicine, providing
      more helicopters equipped with healthcare facilities, more automated external
      defibrillators, and more dedicated neuro-vascular units.--First aid training must
      be made widely available. The French National Academy of Medicine has approved
      ten recommendations regarding organization and facilities.

PMID- 23550451
TI  - [Conditions for the survival of combat casualties in overseas operations:
      procedure and experience from the Afghan out-of-hospital theater].
AB  - Recent conflicts have led the French Army Health Service to specify the setting
      condition for the survival of combat casualties in overseas operations. The
      majority of them are victims of explosion injuries, and an early and effective
      control of bleeding is the primary means of improving survival. A procedure
      called "Combat Rescue" is taught. This chronological procedure favours external
      haemostasis and led to specific equipment, in particular a tourniquet and a
      haemostatic bandage of high efficiency. It is applied in recent years on the
      Afghan out-of-hospital theatre. A very front medical presence, which is
      systematic during evacuations, is a feature of the French Army Health Service
      operations support.

PMID- 23550452
TI  - [Primary emergencies: management of acute ischemic stroke].
AB  - The emergency diagnostic strategy for acute ischemic stroke consists of:-
      identification of stroke, based on clinical examination (sudden onset of a focal
      neurological deficit);--identification of the ischemic or hemorrhagic nature by
      MRI or CT;--determination of the early time-course (clinical examination) and the
      cause. In all strokes (ischemic or hemorrhagic), treatment consists of:--the same
      general management (treatment of a life-threatening emergency, ensuring normal
      biological parameters except for blood pressure, and prevention of
      complications);--decompressive surgery in the rare cases of intracranial
      hypertension. For proven ischemic stroke, other therapies consist of: rt-PA for
      patients admitted with 4.5 hours of stroke onset who have no contraindications,
      and aspirin (160 to 300 mg) for patients who are not eligible for rt-PA. These
      treatments should be administered within a few hours. A centralized emergency
      call system (phone number 15 in France) is the most effective way of achieving
      this objective.

PMID- 23550453
TI  - [Beyond the heart: towards greater public awareness of life-threatening
      emergencies].
AB  - More than any other circumstances, life-threatening emergencies require rapid and
      appropriate management. Public involvement is, in many cases, essential for
      optimal outcome. The victim, a relative or a bystander, if they do the right
      thing, can facilitate emergency service intervention. Adult sudden cardiac death
      is one area where public involvement has been particularly encouraged. Based on
      this experience, the aim of this article is to examine possible extension to
      other life-threatening emergencies, as well as the consequences of this
      involvement in terms of public health and community awareness.

PMID- 23550454
TI  - [Territorial and social healthcare inequalities in France].
AB  - Geographic analyses of health-related issues have a long tradition in France, and
      have often consisted of observational studies conducted by practitioners
      themselves. Such geographic approaches were gradually abandoned during the 20th
      century as the pace of clinical progress increased. The few healthcare studies
      conducted by geographers have had little impact among the medical community.
      However, our studies show that geographic inequalities in health still persist.
      During the last 10 years or so, the social and economic crisis has dangerously
      accentuated health inequalities at every level In France, where equality is
      supposed to be the watchword of the entire healthcare system, this situation is
      particularly regrettable. Access to care decreases with distance from medical
      services. With the increasing urban and suburban concentration of the population,
      public healthcare policy must focus on finding solutions for people living in
      remote areas or too poor to access medical care. Geographic analyses of
      healthcare organization can help to make medical care available for all,
      especially those who need it most.

PMID- 23550455
TI  - [Diabetes and social deprivation].
AB  - BACKGROUND: Diabetes prevalence is frequently associated with low socioeconomic
      status (SES), but little is known about the relationship between SES and diabetes
      control, follow-up and quality of life. We evaluated SES by using the EPICES
      score, an individual index of deprivation (Evaluation de la Precarite et des
      Inegalites de Sante dans les Centres d'Examen de Sante; Evaluation of
      Precariousness and Inequalities in Health Examination Centers). A total of 1686
      subjects aged from 25 to 85 years were selected at random in Montpellier and 154
      in Narbonne, of whom 126 were managed by a care network including diabetologists,
      general practitioners and nurses. Capillary glycemia, the body mass index (BMI),
      waist circumference (WC), and blood pressure were measured in all the subjects.
      HbA1c was measured in subjects with above-normal glycemia. Five hundred sixty
      four subjects from the study population (190 diabetic patients, 292 subjects with
      non diabetic hyperglycemia, and 86 euglycemic subjects) were clinically evaluated
      and asked to complete a questionnaire covering socioeconomic status and diet. The
      data were then compared between deprived and non deprived subjects. One hundred
      sixty-one diabetic patients had a clinical examination and completed a detailed
      questionnaire including their history, therapy, control and follow-up of
      diabetes, perception of diabetes, quality of life, socioeconomic status and diet.
      The data were then compared between deprived and non deprived patients. One
      hundred twenty-six diabetic subjects managed by the AUDIAB care network were
      compared with 163 diabetics recruited in Montpellier, based on the same
      investigations and the same questionnaires. The data were compared between the
      overall patients and between deprived and non deprived patients. In the overall
      population, deprived subjects were younger and more frequently smokers, and had
      higher BMI than non deprived subjects. The overall prevalence of type 2 diabetes
      was 8.1%. Among patients younger than 65 years, deprived subjects had a higher
      prevalence of diabetes and non diabetic hyperglycemia than non deprived subjects
      (6.9% vs 4.4% and 22.8% vs 19.5%). More are unmarried males and 33% present with
      a significant level of education (secondary or university). Deprivation was
      associated with transport difficulties, vehicle acquisition, living in a private
      house, employment. More have few income to buy food and a large number use
      economic stores. They eat few proteins, fresh vegetables, fruits, dairy products
      and more often rice, pasta, tea, coffee and soft drinks. Most have their meals
      outside in economic restaurants. Dental problems are very common. 161 diabetic
      patients were evaluated Deprived diabetics were younger, more frequently males,
      more smokers with an increased BMI and WC. Among deprived diabetic patients,
      diabetes was diagnosed later on and less often by a systematic inquiry than in
      the non deprived group. Deprived patients presented with a poorer glycaemic
      control, more hypoglycaemic and ketosis events than non deprived subjects. They
      present with more difficulties to accept dietary and antidiabetic drugs. Insulin
      was less frequently used. Quality of life was impaired with an increased
      prevalence of anxiety and depression. Diabetic patients treated in the "Reseau de
      soins AUDIAB" presented with a better control of their disease and a better
      quality of life than patients treated out of the "Reseau". These data were
      confirmed whatever the level of deprivation.

PMID- 23550456
TI  - [Chronic renal disease and dialysis in China].
AB  - In China, the prevalence of chronic kidney disease (CKD) prevalence is about 10%.
      Together with cardio-vascular disorders, CKD is now a major public health
      challenge. The annual Chinese incidence of end-stage kidney diseases in China is
      36 cases per million inhabiants. In year 2010, the national dialysis registry,
      included 310 000 patients; 11 000 of them were living in Shanghai mean age 56
      years M/F sex ratio 1.82. A governement program is underway to prevent and to
      detect CKD in China.

PMID- 23550457
TI  - [Analysis of 2000 heart transplant, procedures at la Pitie Hospital].
AB  - Since the first procedure carried out at La Pitie Hospital, on 27 April 1968, we
      have performed 1918 heart transplants. We analyzed outcomes in four successive
      periods: initial experience from 1968 to 1981 (53 patients), using early
      immunosuppressive regimens; an expansion phase (839 patients) from 1982 to 1992,
      with the introduction of cyclosporine; a stabilisation phase (522 patients) from
      1993 to 2003; and the most recent phase (504 patients) from 2004 to 2010. We
      focused particularly on the most recent period. National super-emergency "rules
      were created, and grafts from older," "borderline" donors were used. Hyperimmune
      recipients started to be grafted, and ECMO was frequently used during the
      preoperative and postoperative periods. Due to limited organ availability, we
      have gradually placed more and more patients on mechanical cardiac support as a
      bridge to transplantation. Their quality of life is improved.

PMID- 23550458
TI  - [Hypertrophic cardiomyopathy: current aspects and new developments].
AB  - Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by left
      ventricular hypertrophy with no apparent cause (such as severe hypertension,
      aortic valve stenosis, etc.). The clinical diagnosis is based on cardiac imaging,
      commonly using 2D echocardiography and increasingly CMR. HCM is the leading cause
      of sudden death in young people, especially on the sports field. Many patients
      remain asymptomatic throughout life, while others develop heart failure, atrial
      fibrillation and stroke. HCM is the most common genetic (autosomal dominant)
      cardiovascular disease, with variable penetrance and expression. It is caused by
      mutations in genes coding for cardiac sarcomeric proteins. Genetic counseling and
      clinical risk stratification are crucial for all patients. Medical treatment with
      B-blockers or verapamil improves symptoms but has not been show to modify the
      clinical course. Patients with outflow obstruction and severe symptoms
      unresponsive to medical therapy are candidates for alcohol septal ablation or
      surgical myectomy. Current approaches focus on the prevention of sudden death by
      means of implantable defibrillators in high-risk patients.

PMID- 23550459
TI  - [The Sino-French emergency and disaster medicine training center].
AB  - French (AP-HP) and Chinese (Beijing Health Office) hospitals, with support from
      the French company Total, collaborated in order to improve Chinese doctors'
      knowledge of emergency and disaster medicine prior to the Beijing Olympic Games.
      A Sino-French emergency and disaster medicine training center was subsequently
      opened in Beijing in 2008, with the aim of providing high-level continuous
      medical training for Chinese specialists in emergency medicine. Teaching in the
      management of critical situations was based on the use of a latest-generation
      simulator (Sim 3G; Laerdal). This collaboration has had both pedagogical and
      diplomatic benefits.

PMID- 23550460
TI  - [Drug prescription to elderly patients].

PMID- 23550461
TI  - Extravasation injuries: current medical and surgical treatment.
AB  - BACKGROUND: Extravasation is a devastating complication of intravenous therapy
      that develops when a drug infiltrates the interstitial tissue surrounding the
      vein. Due to the uncertain and possibly dramatic outcome, early recognition and
      adequate treatment with the aid of a standardized protocol are needed. METHODS: A
      pubmed literature search was conducted and all relevant articles were reviewed
      for the development of an extravasation treatment protocol. RESULTS: An overview
      of current treatment guidelines and clinical experience is provided. The
      extravasation treatment protocol was implied during 1 year in this university
      hospital with satisfactory outcome. CONCLUSION: Treatment starts with prevention.
      In case of an established extravasation injury, early recognition, assessment of
      severity, and treatment with medical and/or surgical therapies are recommended.

PMID- 23550462
TI  - Effect of ginger extract on liver damage in experimental obstructive jaundice
      produced by main bile duct ligation.
AB  - BACKGROUND: Obstructive jaundice is one of the most important surgical causes of
      childhood jaundices. The aim of this study is to investigate effects of ginger
      (Gingiber officinalis) extracts on liver damage in experimental obstructive
      jaundice produced by main bile duct ligation. MATERIALS AND METHODS: Forty two
      Wistar-albino rats were randomly allocated into 7 groups (n = 6). Nothing was
      performed in the control (C) group. Only laparatomy was performed in the sham
      (Sh) group. The ginger 1 and 2 (G1 and G2) groups received only 100 and 200
      mg/kg/day doses of ginger extract for 1 week orally. In study group, common bile
      duct ligation was done. In treatment 1 and 2 (T1 and T2) groups common bile duct
      ligation was followed by administration of 100 and 200 mg/kg/day doses of ginger
      extract for 1 week orally from the third post operative day, respectively. Blood
      samples and liver were harvested in order to evaluate the serum aspartate
      aminotransferase (AST), alanine amino transferase (ALT), gama glutamyltransferase
      (GGT), total bilirubin (bil), superoxide dismutase (SOD), glutathione (GSH),
      malondialdehyde (MDA) and liver tissue SOD, GSH, MDA levels and liver apoptosis.
      Results were analyzed by Mann-Whitney U test statistically. RESULTS: Ginger
      administration did not result in any differences of serum or tissue levels of the
      studied parameters and liver apoptosis between the groups statistically (except
      AST levels in group T2). Tissue GSH and serum SOD levels were only mildly
      increased in groups receiving ginger alone. CONCLUSIONS: There is no evidence for
      protective, inhibitive and decreasing effects of ginger extract on liver injury
      in experimental obstructive jaundice with these findings.

PMID- 23550463
TI  - Long term outcomes following emergency intensive care readmission after elective
      oesophagectomy.
AB  - OBJECTIVE: The purpose of this study was to analyse the outcomes of patients
      readmitted to ICU following initial recovery after oesophagectomy. BACKGROUND:
      Surgery for oesophageal cancer has significant morbidity and poor long-term
      outcomes. There is limited evidence concerning the long-term outcomes of patients
      who require readmission to the intensive care unit (ICU) after an initial
      recovery following resection. METHOD: The case notes of 221 patients who
      underwent elective oesophagectomy over an eleven-year period were reviewed.
      Patients who were readmitted to ICU following initial recovery were identified
      and the clinical and demographic characteristics of these patients were
      prospectively recorded and their outcomes analysed. RESULTS: A total of 43
      patients were readmitted to ICU during the study period mainly for respiratory
      complications or anastomotic leaks. 17 patients (40%) required a period of
      mechanical ventilation; 16 patients (37%) required inotropes and 2 patients (5%)
      required renal support. The mean ICU stay on readmission was 8 days (range 0-49
      days) with an in-hospital mortality rate of 33%. In terms of long-term outcomes,
      the actuarial two- and five-year survival rates were 42.3 +/- 7.7% and 36.7 +/-
      8.5% respectively. Multivariate analysis identified both age (Hazard ratio: 1.05
      +/- 0.02; p = 0.04) and requirement for renal support (Hazard ratio: 5.63 +/-
      0.8; p = 0.03) as independent adverse predictors of survival. CONCLUSIONS:
      Although ICU readmission following elective oesophagectomy is associated with
      significant mortality, the overall long-term survival rate for these patients,
      particularly those who do not require renal support is encouraging.

PMID- 23550464
TI  - MUC1 and bcl-2 expression in preinvasive lesions and adenosquamous carcinoma of
      the lung.
AB  - BACKGROUND: Adenosquamous carcinoma of the lung involves both adenocarcinoma and
      squamous cell carcinoma, each comprising at least 10% of the tumor. Atypical
      adenomatous hyperplasia (ADH), bronchiolar columnar cell dysplasia (BCCD), basal
      cell dysplasia (BCD), columnar cell dysplasia (CCD), bronchial epithelial
      dysplasia with transitional differentiation (BEDT) and squamous dysplasia (SD)
      are preinvasive lesions. The aim of this study is to define the preinvasive
      lesions and evaluate the role of MUC1, bcl-2, and the preinvasive and invasive
      components of adenosquamous carcinoma. METHODS: A group of 31 patients with
      adenosquamous carcinoma of the lung were selected. The ratio of squamous to
      glandular differentiation, the associated preinvasive lesions, the features of
      peritumoral tissue, the stroma of the tumor, necrosis, perineural and vascular
      invasion were analyzed. For the immunohistochemical study, blocks containing
      squamous cell carcinoma, adenocarcinoma and preinvasive lesions were selected.
      MUC1 and bcl-2 analyses were performed by the immunoperoxidase method using the
      avidin-biotin complex. RESULTS: Associated preinvasive lesions amd SD, BCCD,
      BEDT, AAH and CCD were observed in 24, 6, 3, 1 and 6 cases, respectively.
      Expression for MUC1 was positive in the squamous component of 30 cases, the
      adenocarcinoma component of 27 cases and in 34 preinvasive lesions. A strong
      correlation was found between MUC-1 expression in the squamous component and
      tumor localization (p = 0,01). The positive expression of Bcl-2 in the
      adenocarcinomatous component was correlated with the presence of preinvasive
      lesions (p = 0,01). CONCLUSIONS: Squamous dysplasia was the most frequent
      preinvasive lesion of adenosquamous carcinomas. MUC1 and bcl-2 expression levels
      were strongly associated with preinvasive lesions in adenosquamous carcinomas.

PMID- 23550465
TI  - The use of single incision thoracoscopic surgery in diagnostic and therapeutic
      thoracic surgical procedures.
AB  - BACKGROUND: As a minimal invasive procedure, a standard threeportal
      videothoracoscopy may have complications such as chronic and residual pain.
      However, a single incision thoracoscopic surgery is a less invasive procedure
      with minimal complications. We present our series of patients who had single
      incision thoracoscopic surgical procedures. PATIENTS AND METHODS: A total of 49
      patients, 29 (59.2%) male and 20 (40.8%) female with a mean age of 45.7 +/- 17.6
      years (range, 16 to 86 years) underwent a total of 59 single incision
      thoracoscopic surgical procedures. We most often made a 2-2.5 cm single incision
      on the seventh or eighth intercostal space at the midaxillary line. VAS (Visual
      analogue scale) scores for pain at postoperative day 1 and the mean of chest tube
      removal times were recorded for each procedure. The patients were discharged
      following chest tube removal. RESULTS: We performed an overall of 59 procedures
      including 8 (13.7%) wedge resections for either histologic diagnosis or
      spontaneous pneumothorax, 4 (6.8%) pleural biopsies, 23 (38.9%) pleurectomies, 9
      (15.2%) deloculation and decortications, 5 (8.6%) traumas in and 10 (17.5%)
      sympathectomies. No patient required an additional thoracoscopic port or
      conversion to thoracotomy. The overall mean of postoperative VAS scores for all
      procedures at postoperative day 1 and day 30 were 3.2 +/- 0.9 and 1.4 +/- 0.5,
      respectively (p <0.0001). The overall mean of chest tube removal time was 2.3 +/-
      0.8 days (median; 2). We observed neither morbidity nor mortality. CONCLUSIONS:
      In selected patients, single incision thoracoscopic surgery is an effective and a
      safe procedure with lower levels of pain and shorter hospital stay. A wide
      spectrum of thoracic surgical procedures can be performed with the use of single
      incision thoracoscopic surgery.

PMID- 23550466
TI  - Management of colovesical fistulae caused by diverticulitis: 12 years of
      experience in one medical centre.
AB  - BACKGROUND: Diverticulitis can be complicated by a colovesical fistula (CVF).
      This phenomenon is relatively uncommon in surgical practice. The aim of this
      study was to evaluate diagnostic and surgical management of CVF at our medical
      centre. MATERIAL AND METHODS: In this retrospective study, details of 31 patients
      undergoing surgery for CVF between January 1998 and March 2010 were recorded.
      These patient records were analysed for presenting symptoms, diagnostic
      investigations and surgical procedures. RESULTS: The most common presenting
      symptoms were pneumaturia, urinary tract infections, abdominal pain, and
      fecaluria. CT identified CVF in 28 patients (92.2%), cystoscopy in 4 patients
      (23.5%), and barium enema in 3 patients (13.6%). Surgical management was
      resection of the diseased colon segment with primary anastomosis in 29 of 31
      patients. The bladder fistulae were oversewn and an omental plasty was placed
      between bowel anastomosis and bladder. There was only one postoperative leak and
      one case of mortality (3.2%). CONCLUSIONS: CT is the most sensitive test in
      identifying CVF. Resection of the diseased colon segment and primary anastomosis
      seems to be an effective and safe surgical method for treating CVF. This surgical
      treatment has an acceptable risk for anastomotic leak and mortality.

PMID- 23550467
TI  - Primary hyperparathyroidism in children and young adults:--a single institution
      experience.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is an extremely rare disorder in
      children and young adults. In the literature, only small case series or case
      reports can be found. The aim of this study was to show our experience in the
      management of PHPT patients under the age of 20. METHODS: We performed a
      retrospective study of PHPT patients who underwent surgery in our institution.
      From 2004 to 2010, 522 patients underwent surgery (74, male; 478, female). Of
      these, 7 patients were under the age of 19 (4 [5%], male, 3 [0.6%], female). The
      following was analyzed demographic characteristics, length of the disease,
      clinical presentation, and preoperative and postoperative parathyroid hormone
      (PTH) and serum calcium levels. Ultrasonography, scintigraphy, and computerized
      tomography were performed for preoperative localization, and the types of
      operations and histopathological findings were assessed. RESULTS: The average age
      of the patients was 15.7 years. Average duration of disease was 4.8 months. Only
      2 patients (28%) were asymptomatic. The mean serum calcium level was 3.06 mmol/l,
      and the mean PTH level was 620.6 pg/ml. Both parameters showed significant
      reduction after surgery. One patient was positive for multiple endocrine
      neoplasia type I syndrome, while the other patients were sporadic. Five
      parathyroidectomies (72%), 1 double parathyroidectomy (14%), and 1 subtotal
      parathyroidectomy (14%) were performed. CONCLUSION: PHPT in children and young
      adults is rare. It occurs more frequently in young adults than in children, with
      slight predominance in males. Most of the patients are symptomatic at diagnosis.
      Surgery is a successful method of treatment.

PMID- 23550468
TI  - A very nervous inguinal floor: report of a case.
AB  - Chronic pain after inguinal hernia repair with prosthetic meshes is recorded in
      some patients. Although the exact etiology of the pain is not fully understood,
      it can be related to the trauma to the regional nerves. It is possible to involve
      these nerves by injuring, suturing, stapling, tacking or compressing them during
      the operation. Therefore, a delicate surgical approach to the inguinal floor with
      correct identification of three nerves is necessary for patient comfort at early
      and late postoperative period. We herein report a surgical view of an inguinal
      floor which are very rich of neural structures in a patient undergo an elective
      inguinal hernia repair. The number of the main nerve bundles was excessive, and
      they were thicker than generally met. This kind of anatomic variations may create
      a difficulty for repair with prosthetic material. The identification of the nerve
      structures was hard at first sight and the correct identification was only made
      by consulting the surgical picture with a senior anatomist.

PMID- 23550469
TI  - Feasibility of laparoscopic resection of mesenteric cysts: two case reports.
AB  - INTRODUCTION: Mesenteric cysts (MC) are rare intra-abdominal tumors. The
      incidence has been estimated to be 1/100000 in the adult population and 1/20000
      in children, with a male: female ratio of 1:1. The first successful laparoscopic
      resection of a MC was reported by MACKENZIE et al. in 1993. The malignant
      transformation appears in 3% of cases. In our study, we presented the feasibility
      and results of laparoscopic resection. CASE REPORTS: We report two cases of
      mesenteric cysts removed by a laparoscopic procedure. RESULTS: Laparoscopic
      approach in the two cases was successful. No conversion was observed. No
      complication occurred. The histopathological studies revealed no malignancy.
      After 18 months of follow-up the 2 patients remained free of disease. CONCLUSION:
      In selected cases, safe and complete resection of MC could be achieved by
      laparoscopic approach. Complete surgical resection of MC is the treatment of
      choice when the cyst becomes symptomatic or when complications occur.

PMID- 23550470
TI  - Floating aortic thrombus: the endovascular approach.
AB  - CASE REPORT: We report a 71-year-old obese white female who presented with sudden
      right calf pain after a long distance flight. Symptoms were initially regarded as
      venous in origin. Duplex investigation ruled out deep vein thrombosis. Ultimately
      she presented to our department with complaints of claudication. Clinical
      evaluation and a new duplex scan showed occlusion of the right popliteal artery.
      Further evaluation with CT-angiography showed, besides occlusion of the right
      popliteal artery, a floating thrombus in the infrarenal abdominal aorta. The
      thrombus was treated with a bare-metal stent placed through a femoral approach.
      CT-scans at 1 and 3 months demonstrated complete exclusion of the thrombus. The
      claudication of the right calf resolved spontaneously. Floating thrombus of the
      infrarenal abdominal aorta is a rare cause of distal arterial embolisation. CT
      scan with contrast enhancement is the preferred diagnostic technique.
      Endovascular repair seems to be the treatment of choice and in our opinion a
      covered stent is not required. Anticoagulation therapy needs to be guided on an
      individual patient basis

PMID- 23550471
TI  - Intrathymic parathyroid adenoma presenting with seizures.
AB  - A 59-year-old diabetic patient was admitted with loss of consciousness and
      convulsions. Hypercalcaemia and hypoglycaemia were discovered. Computed
      tomographic and technetium scans revealed a retrosternal paramedian nodule.
      Radical thymectomy was performed by median sternotomy. Diagnosis of intrathymic
      parathyroid adenoma was made. One year later the patient had good diabetes
      control without clinical symptoms.

PMID- 23550472
TI  - Abdominal wall desmoid tumours.
AB  - We present two cases of desmoid tumour of the anterior abdominal wall in young
      women in whom the defect after radical excision could not be closed without using
      prosthesis. The first case warranted the use of a composite mesh, the second a
      polypropylene prosthesis. In both cases primary closure of the skin was possible.
      Both women are doing fine with no sign of relapse or incisional hernia.

PMID- 23550473
TI  - Acute hernial strangulation following Wii Fit exercises.
AB  - The Wii Fit is one the most popular fitness games on the market. Although this
      device has been linked to a number of injuries, the vast majority of these have
      been relatively minor musculo-skeletal complaints. We present a case of a patient
      who presented with an acute strangulation of a pre-existing asymptomatic
      paraumbilical hernia after completing a series of aerobic exercises on her Wii
      Fit. She required laparotomy and small bowel resection for infarcted bowel.
      Although a number of minor mechanical and orthopaedic injurieshave been reported
      with the Wii Fit, this represents the first case of a life-threatening
      complication associated with the use of this device.

PMID- 23550474
TI  - Spontaneous, isolated caecal necrosis: report of a case, review of the
      literature, and updated classification.
AB  - Isolated necrosis of the caecum is a rare cause of abdominal pain. In the absence
      of occlusive vascular disease it has a number of well documented associations,
      the commonest of which is patients' receiving haemodialysis for endstage renal
      failure. It has also been associated with shock states, cardiac failure,
      ischaemic heart disease, diabetes and drugs such as cocaine, thiopentone and
      cytotoxic agents. However, there are few reported cases in the literature without
      the aforementioned associations and the majority of cases, regardless of
      aetiology, were treated with either hemicolectomy or wedge resection and
      ileocolic anastamosis. This report describes a case of isolated caecal necrosis,
      mimicking acute appendicitis, successfully treated by local excision of the
      necrotic segment. It also provides a systematic review of the literature and
      proposes an updated classification of associations in isolated caecal necrosis.

PMID- 23550475
TI  - Practical application of using local anaesthetics: surgical perspectives.
AB  - With reduction in surgical training, surgical trainees may find it difficult deal
      with local anaesthetic agents because of lack of exposure and knowledge. We have
      summarised the common usage of local anaesthetics in various situation. The
      trainees need to gain competence by understanding the basics and practising them
      under supervision.

PMID- 23550476
TI  - "Staff must be protected when they raise concerns".

PMID- 23550477
TI  - Protect nurses who speak out.

PMID- 23550479
TI  - "Cartel" calls for further cuts in nurse pay.

PMID- 23550478
TI  - Whistleblower forced to pay trust's legal bills backs campaign.

PMID- 23550480
TI  - "We will stand by you if you speak out when things are going wrong".

PMID- 23550481
TI  - Is action taken when nurses raise concerns about patient care?

PMID- 23550482
TI  - "Does the McDonald's business model suit modern healthcare?".

PMID- 23550483
TI  - Developing skills in clinical leadership for ward sisters.
AB  - The Francis report has called for a strengthening of the ward sister's role. It
      recommends that sisters should operate in a supervisory capacity and should not
      be office bound. Effective ward leadership has been recognised as being vital to
      high-quality patient care and experience, resource management and
      interprofessional working. However, there is evidence that ward sisters are ill
      equipped to lead effectively and lack confidence in their ability to do so.
      University College London Hospitals Foundation Trust has recognised that the job
      has become almost impossible in increasingly large and complex organisations.
      Ward sisters spend less than 40% of their time on clinical leadership and the
      trust is undertaking a number of initiatives to support them in this role.

PMID- 23550484
TI  - Why management skills are a priority for nurses.
AB  - Newly qualified nurses and new nurse managers are often expected to hit the
      ground running with no management training. Management skills are as important as
      leadership skills in addressing some of the failings identified in the Francis
      report. A management framework is required to provide a consistent approach to
      management development for all staff in healthcare, irrespective of discipline,
      role, function or seniority.

PMID- 23550485
TI  - How to turn ward managers into leaders.
AB  - Ward managers are the largest management group in the NHS, and have an important
      leadership role in creating and sustaining excellent performance. Two London
      foundation trusts developed a unique frontline leadership programme for these
      staff.

PMID- 23550486
TI  - Redefining the ward sister role to boost frontline care.

PMID- 23550487
TI  - Meeting spiritual needs in mental health care.
AB  - Belief in Recovery is a project introduced into Northumberland, Tyne and Wear
      Foundation Trust between 2010 and 2012 to develop nursing staff members'
      confidence and skills in meeting the spiritual, religious and cultural needs of
      patients in mental health recovery. This article describes how we assessed and
      understood their training needs and developed a training programme, and how this
      led to positive outcomes for staff.

PMID- 23550488
TI  - An all-inclusive package.

PMID- 23550489
TI  - Think positively to operate at your best.

PMID- 23550490
TI  - F1RST and fall prevention.

PMID- 23550492
TI  - Exploring the integration of internationally educated occupational therapists
      into the workforce.
AB  - BACKGROUND: British Columbia (BC) is a popular Canadian work destination for
      occupational therapists from around the world. PURPOSE: This study explored the
      experiences of stakeholders involved in the integration of internationally
      educated occupational therapists (IEOTs) into the BC workforce. METHOD: Semi
      structured interviews were conducted with the three primary stakeholder groups
      (40 IEOTs, 12 supervising occupational therapists, seven managers), as well as
      with seven key informants. Participants were purposively sampled and thematic
      analysis was applied to the data. FINDINGS: Three themes were identified that fit
      sequentially along a workforce-integration continuum: "coming to Canada,"
      "registering with the college," and "integrating into the workplace." Within
      those themes, findings were organized into two categories, "ingredients for
      success" and "stumbling block," and multiple subcategories. IMPLICATIONS: The
      findings suggest that hiring IEOTs can bring benefits to the workplace and
      clients. However, changes made along the continuum would facilitate workforce
      integration, ultimately benefiting all stakeholders. These findings may be of
      interest to IEOTs, occupational therapists, and managers as well as individuals
      working in regulation and policy.

PMID- 23550493
TI  - Validity of predischarge measures for predicting time to harm in older adults.
AB  - BACKGROUND: Concern is often expressed about the ability of persons with
      cognitive impairment to manage safely after discharge home from hospital.
      Measures validated for predicting safety are required. PURPOSE: The purpose of
      this study was to determine whether two predischarge functional measures were
      valid for predicting time to incident of harm after discharge. METHOD:
      Participants (n = 47) were recruited from an inpatient rehabilitation unit. The
      Assessment of Motor and Process Skills (AMPS) and Cognitive Performance Test
      (CPT) were administered in hospital. Incident-of-harm outcome was measured by
      caregiver telephone questionnaire monthly for 6 months. FINDINGS: Compared with
      all independent variables, AMPS Process scale was the best single predictor of
      time to incident of harm (p = .01). CPT had a high specificity (91%) for
      identifying persons who did not have harm. IMPLICATIONS: Both AMPS and CPT
      demonstrated predictive validity for harm outcome over less predictive variables,
      such as comorbidities and activities-of-daily-living burden of care.

PMID- 23550494
TI  - [Conceptualization of the role of expert in enabling occupation by occupational
      therapy fieldwork supervisors].
AB  - BACKGROUND: The use of occupation-focused language in clinical settings is
      essential to supervision of student occupational therapists since training is
      based, at least in part, on the competencies described in The Profile of
      Occupational Therapy Practice in Canada (Canadian Association of Occupational
      Therapists, 2007). PURPOSE: This article describes how occupational therapists
      conceptualize the competencies related to the role of "expert in enabling
      occupation." METHODS: Qualitative data collected from 56 occupational therapists
      across eight focus groups were categorized using content analysis through a
      process of constant comparison. FINDINGS: Although the use of occupation-focused
      language is not widespread, the examples reported in the present study reflect
      occupation-focused client-centred practice. IMPLICATIONS. The use of occupation
      focused language associated with the role of "expert in enabling occupation" can
      be fostered through discussion groups in the context of academic and clinical
      setting collaborations.

PMID- 23550495
TI  - Pre-driving evaluation of a teen with attention deficit hyperactivity disorder
      and autism spectrum disorder.
AB  - BACKGROUND: Vehicle crashes are the leading cause of death among teens, and those
      teens with attention-deficit/hyperactivity disorder and autism spectrum disorder
      (ADHD/ASD) may have a greater crash risk. PURPOSE: This case study compared the
      pre-driving skills of a teen with ADHD/ASD to an age- and gender-matched healthy
      control (HC). METHOD: Data were collected from performance on clinical tests and
      on a driving simulator. FINDINGS: The main impairments of the teen with ADHD/ASD
      were the ability to shift attention, perform simple sequential tasks, integrate
      visual-motor responses, and coordinate motor responses, whereas the HC
      demonstrated intact skills in these abilities. The teen with ADHD/ASD made 44
      driving errors during the drive, and the HC made 17. The teen with ADHD/ASD had
      more lane maintenance, visual scanning, and speeding errors compared to the HC.
      IMPLICATIONS: Teens with ADHD/ASD may have more pre-driving deficits and may
      require a certified driving rehabilitation specialist to assess readiness to
      drive, but a larger study is needed to confirm this.

PMID- 23550496
TI  - Teaching mindfulness to occupational therapy students: pilot evaluation of an
      online curriculum.
AB  - BACKGROUND: How mindfulness can be learned by occupational therapy students to
      manage their own self-care processes has not been fully examined as yet. PURPOSE:
      This article describes an online curriculum approach for teaching a general
      introductory mindfulness course and examines outcomes with master's entry-level
      occupational therapy students. METHOD: Fifteen students participated in an 8-week
      online mindfulness curriculum and completed a pre- and post-training survey. The
      Mindfulness Attention and Awareness Scale (MAAS) was used to measure mindfulness.
      Demographic, MAAS-scored mindfulness, and clinical utility data were collected.
      RESULTS: Results showed a statistically significant change (t = -4.82, p = 0.002)
      in MAAS mindfulness scores from the program start to end. Informal practice
      exercises and guided meditations were perceived by participants as being more
      helpful ways for developing an understanding and approach to mindfulness than
      were readings about mindfulness. IMPLICATIONS: This study suggests that
      mindfulness can be taught using an online approach.

PMID- 23550497
TI  - Community integration outcomes after traumatic brain injury due to physical
      assault.
AB  - BACKGROUND: Community integration is considered an ultimate goal for
      rehabilitation after traumatic brain injury (TBI). PURPOSE: To determine (a)
      whether differences exist in rehabilitation outcomes between intentional and
      unintentional TBI populations and (b) whether TBI from assault is a predictor of
      community integration following inpatient rehabilitation. METHOD: Retrospective
      cohort study using population-based data from Canadian hospital administration
      records, 2001 to 2006. Outcome measure was the Reintegration to Normal Living
      Index (RNLI). FINDINGS: From a sample of 243 persons, 24 (9.9%) had sustained TBI
      from physical assault. Persons with TBI from physical assault reported
      significantly lower scores on two items on the RNLI's Daily Functioning subscale:
      "recreation" and "family role." IMPLICATIONS: These findings suggest that
      targeted intervention in these specific areas could be beneficial, which are
      often primarily addressed by occupational therapists in both inpatient
      rehabilitation and community settings.

PMID- 23550498
TI  - The British Association for the Study of Community Dentistry at forty: our
      professional project.

PMID- 23550499
TI  - Challenges encountered when conducting a dental health needs assessment of older
      people resident in care homes: experience from England.
AB  - This paper describes the process of undertaking a dental health needs assessment
      of older people resident in care homes in the North East of England and the
      challenges involved. It illustrates many competency areas of interest to dental
      public health practitioners: oral health surveillance, dental public health
      intelligence and collaborative working.

PMID- 23550500
TI  - Rare diseases with oral components: care course and quality of life.
AB  - AIM: To describe links between the care course of individuals suffering from rare
      diseases and socio-behavioural risk factors and to ascertain the impact of dental
      conditions on the quality of life. DESIGN: A cross-sectional comparative study
      involving self-reported questionnaire was performed. Care course was evaluated
      using predisposing, enabling and needs factors. The impacts of dental conditions
      on quality of life were measured with the OHIP 14 questionnaire. Proportions were
      compared by Chi-square test. Logistic regression for multivariate analysis
      assessed statistical association between variables. RESULTS: Responses were
      received from 355 subjects (mean age 36.9 years, 67.6% females). Thirty-three
      rare diseases were recorded. Respondents were classified as group A, individuals
      suffering from rare diseases with a dental component (n=207, 58.3%), and group B,
      without dental component. Group A reported earlier diagnosis, more positive
      attitude toward dentists, functional limitation and higher prosthetic treatment
      needs. Only 17.4% of subjects having fewer than 20 teeth wear prosthetics. A
      higher percentage of individuals claiming pain, physical disability,
      psychological discomfort and social disability, was found among group B
      (p<0.001). Logistic regression analysis retained two impact factors:
      psychological disability (Exp(B)=8.66; 95% CI 1.86-40.34) and social wellbeing
      (Exp(B)=0.06; 95% CI 0.02-0.215). CONCLUSION: Rare diseases with a dental
      component benefited from earlier identification of symptoms. Dentists could
      contribute to patients' quality of life by helping in early diagnosis, reducing
      functional limitation and improving social wellbeing.

PMID- 23550501
TI  - Fluoridation and dental caries severity in young children treated under general
      anaesthesia: an analysis of treatment records in a 10-year case series.
AB  - OBJECTIVE: To compare the severity of dental caries in the primary dentitions of
      children under 7 years (who received comprehensive restorative treatment under
      general anaesthesia, GA) from an optimally fluoridated area (0.85 ppmF) and a low
      fluoride area (approximately 0.1 ppmF). RESEARCH DESIGN: Consecutive clinical
      case series: clinical details (diagnoses and the treatments provided) were
      recorded for children who had received comprehensive dental care under GA between
      2000 and 2009. Age, gender, ethnicity, socio-economic status and fluoridation
      status (determined from the residential address) were also recorded. RESULTS: Of
      the 1396 treated children, 55.7% came from fluoridated areas and 52.5% were male.
      On average, children from low-fluoride areas were 2.4 months younger and
      presented with more decayed deciduous teeth than those from fluoridated areas
      (4.9 and 3.9 teeth respectively; p<0.0001). For each tooth type, the mean number
      of carious teeth at presentation was greater among the children from low-fluoride
      areas. In the multivariate model, the number of deciduous teeth affected by
      caries was lower among older children, those residing in a fluoridated area and
      among those seen after 2001. It was higher among those not living in high-SES
      areas. CONCLUSIONS: Children with severe dental caries had statistically
      significantly lower numbers of lesions if they lived in a fluoridated area. The
      lower treatment need in such high-risk children has important implications for
      publicly-funded dental care.

PMID- 23550502
TI  - Measuring determinants of oral health behaviour in parents of preschool children.
AB  - OBJECTIVE: The aim of this study was to develop a valid and reliable measure for
      oral health behaviour and its determinants in five-year-old Flemish children,
      based on the Theory of Planned Behaviour (TPB) and to test its predictive
      validity. METHODS: 1157 parents of five-year-olds completed a questionnaire
      measuring three behaviours related to oral health among children (dietary habits,
      oral hygiene, dental attendance) and their determinants (attitude, subjective
      norms, perceived behavioural control, intention). The sample was randomly split
      in two halves and principal component analyses were performed on one half sample
      to identify the factor structure. Confirmatory factor analyses were performed on
      the remaining half sample to obtain a cross-validation. Predictive validity was
      tested using multiple regression analyses. RESULTS: For each behaviour four
      component structures reflecting the TPB-dimensions, accounting for 44% to 55% of
      the variance were retrieved and confirmed in the cross-validation. Internal
      consistency (Cronbach's alpha) of the scales ranged from 0.52 to 0.80. A sizeable
      percentage of variance of intentions and behaviours was explained by the model.
      CONCLUSIONS: The TPB components were significant predictors of intentions and
      behaviours. These findings argue for the reliability and validity of the
      questionnaire for exploring determinants underlying parental oral health
      behaviour.

PMID- 23550503
TI  - The self-reported oral health status and dental attendance of smokers and non
      smokers.
AB  - AIM: To report the oral health status and dental attendance of smokers and non
      smokers. METHODS: A postal survey enquiring about smoking status, stop smoking
      advice, dental attendance and perceptions of oral health was conducted in
      Yorkshire and the Humber, U.K., in 2008. To address potential biases data were
      weighted to account for variations in gender, age and deprivation. Data were
      analysed using descriptive statistics, chi-square tests and binary logistic
      regression. RESULTS: A response rate of 43.1% was achieved (n=10,864). Across all
      deprivation quintiles, smokers (17.5% of respondents) were more likely than non
      smokers to report fair, poor or very poor oral health (p<0.001). Smokers in the
      least deprived areas were more likely than non-smokers to attend the dentist
      symptomatically (p<0.001). Advice to quit was most frequently gained from GP
      services followed by NHS Stop Smoking Services and dental teams. CONCLUSIONS:
      Smokers were more likely than non-smokers to have a poor self-rated oral health
      status and attend the dentist symptomatically, irrespective of deprivation.

PMID- 23550504
TI  - Attitudes towards the use of fluorides for oral health among Islamic clerics in
      Kelantan Province, Malaysia.
AB  - OBJECTIVE: To assess the knowledge, attitudes and practices of Imams (Islamic
      clerics) concerning fluoride toothpaste and fluoridated water to improve oral
      health in Kelantan. BASIC RESEARCH DESIGN: Cross sectional study of Imams in 65
      registered mosques in Pasir Puteh district, Kelantan. METHOD AND PARTICIPANTS:
      Face-to-face interview, using structured questionnaire and some open ended
      questions. RESULTS: Most of the 83 interviewees (82% participation rate) were
      unsure whether their toothpaste contained fluoride (64%), only 25% were sure.
      More than one-third (37%) were using fluoridated piped water. Most (87%) had
      little knowledge of fluorides and more than two-thirds (69%) had lacked positive
      attitudes towards its use. Television (54%) was the most common source of
      information about fluorides, followed by newspapers (9%). The main reasons given
      among the few who opposed fluoride use were i) fear of dangerous side effects
      (4%) and ii) uncertainty about the halal status of fluoride (2%), Attitudes were
      not associated with the use of fluoridated water supply (p=0.999), age (p=0.103),
      income (p=0.540) and location (p=0.999). CONCLUSION: Over two-thirds of Imams had
      little knowledge of and lacked positive attitudes towards fluoride use in
      toothpaste and piped water supplies.

PMID- 23550505
TI  - The views of examiners on the use of intra-oral photographs to detect dental
      caries in epidemiological studies.
AB  - AIM: The aim of the study was to obtain the views of examiners on their
      experience of using intra-oral photographs as a means of detecting caries in
      epidemiological studies compared to an established visual examination method.
      METHOD: A focus group discussion was conducted with five examiners experienced in
      an established visual examination method after they had performed visual dental
      examinations of a sample of children as well as assessed intra-oral photographs
      of the same children. RESULTS: The time taken by examiners to assess intraoral
      photographs becomes extended when compared to performing a visual examination.
      The ability to assess intra-oral photographs on a screen at a convenient time and
      place was considered advantageous. The examiners found it easier to make caries
      detection decisions on intra-oral photographs of primary teeth than permanent
      teeth. Adequate removal of debris and moisture control prior to obtaining the
      photographs were considered important. CONCLUSION: The views of examiners in this
      study suggest that to improve the utility of photographic method, further
      research is needed to determine adequate drying methods for use in the field.
      Consideration should be given to a time-limited, standardised presentation of the
      photographs including the size and resolution. Specific training on caries
      detection from photographs is also required.

PMID- 23550506
TI  - Caries experience and treatment need in adults with intellectual disabilities in
      two German regions.
AB  - OBJECTIVE: The aim of the study was to determine the caries experience, caries
      prevalence, dental treatment need and care index of adults with intellectual
      disabilities living in the German federal states of Baden-Wurttemberg and Sachsen
      which differ distinctly with respect to the socio-economic conditions. RESEARCH
      DESIGN: In 2007, legal custodians of all persons working in special day-care
      institutions (n=2037) were asked to give consent for dental examinations of their
      custodees. Some 21.9% consented. Thus, 428 persons received a dental examination
      in the day-care institutions. RESULTS: The mean age of the participants was 35.5
      years (range 18-64). Caries prevalence was 93.7% (95% CI 91.3-95.9) in Baden
      Wurttemberg and 97.6% (95% CI 96.2-99.0) in Sachsen. All caries-free persons
      (n=19) were younger than 35 years. The mean DMFT of the whole sample was 12.3
      (95% CI 11.6-12.9). Although DMFT values were the same in both German regions,
      persons from Baden-Wurttemberg had more missing teeth than those from Sachsen but
      untreated carious defects were more common in Sachsen. CONCLUSIONS: Dental care
      for those with intellectual disabilities could be better harmonised within
      Germany. Furthermore, specific dental care and dental treatment strategies could
      be introduced in Germany in order to reduce caries prevalence and number of
      extracted teeth in persons with intellectual disabilities.

PMID- 23550507
TI  - Attitudes towards establishing a daily supervised school-based toothbrushing
      programme--determined by Q-sort methodology.
AB  - OBJECTIVES: This study used Q-sort methodology to determine the views of staff
      involved in a national school-based daily toothbrushing programme. METHODS: Q
      methodology is a mixed-method approach in which participants are asked to sort a
      collection of statements according to degree of agreement with them. Factor
      analysis identified subgroups of like-minded participants and revealed areas of
      consensus and disagreement. 24 Community Dental Service staff managing or
      delivering the toothbrushing programme were asked to rank 49 statements derived
      from previous qualitative interviews. RESULTS: Varimax rotation produced a three
      factor solution with five/six participants loading significantly into each group.
      Groups divided largely according to staff role: Factor 1, mainly support workers
      (assistants with no oral-health background); Factor 2, managers; and factor 3,
      oral health educators (dental nurses with teaching qualifications). As staff new
      to the area of oral-health, the views of support workers were of particular
      interest. Unlike others, this group saw Designed to Smile as a unique health
      promotion scheme and wanted to involve as many children as possible, regardless
      of oral-disease risk. Managers' perceptions of issues affecting the establishment
      of the programme differed from those staff in day-to-day contact with the 515
      schools in which the toothbrushing took place. CONCLUSIONS: This study used a
      long established but little used technique to ascertain the commonality of views
      of staff These data may be of value not only in managing the current programme,
      but for anyone who may be considering developing such a toothbrushing scheme.

PMID- 23550508
TI  - Oral health literacy comparisons between Indigenous Australians and American
      Indians.
AB  - OBJECTIVES: To compare oral health literacy (OHL) levels between two profoundly
      disadvantaged groups, Indigenous Australians and American Indians, and to explore
      differences in socio-demographic, dental service utilisation, self-reported oral
      health indicators, and oral health-related quality of life (OHRQoL) correlates of
      OHL among the above. METHODS: OHL was measured using REALD-30 among convenience
      samples of 468 Indigenous Australians (aged 17-72 years, 63% female) and 254
      female American Indians (aged 18-57 years). Covariates included socio-demography,
      dental utilisation, self-reported oral health status (OHS), perceived treatment
      needs and OHRQoL (prevalence, severity and extent of OHIP-14 'impacts').
      Descriptive and bivariate methods were used for data presentation and analysis,
      and between-sample comparisons relied upon empirical contrasts of sample-specific
      estimates and correlation coefficients. RESULTS: OHL scores were: Indigenous
      Australians - 15.0 (95% CL=14.2, 15.8) and American Indians--13.7 (95% CL=13.1,
      14.4). In both populations, OHL strongly correlated with educational attainment,
      and was lower among participants with infrequent dental attendance and perceived
      restorative treatment needs. A significant inverse association between OHL and
      prevalence of OHRQoL impacts was found among American Indians (rho=-0.23; 95% CL
      = -0.34, -0.12) but not among Indigenous Australians. CONCLUSIONS: Our findings
      indicate that OHL levels were comparable between the two groups and lower
      compared to previously reported estimates among diverse populations. Although the
      patterns of association of OHL with most examined domains of correlates were
      similar between the two groups, this study found evidence of heterogeneity in the
      domains of self-reported OHS and OHRQoL.

PMID- 23550509
TI  - Associations between oral health and height in an indigenous Australian birth
      cohort.
AB  - OBJECTIVE: Evidence suggests that taller individuals have better health than
      their shorter counterparts. This study aimed to test the hypothesis that shorter
      participants in wave-3 of the Aboriginal Birth Cohort (ABC) study, a prospective
      longitudinal investigation of Indigenous Australian individuals born 1987-1990 at
      an Australian regional hospital, would have more caries and periodontal disease
      experience than their taller counterparts. METHODS: Data were collected through
      oral clinical examinations, anthropometric measures and self-report
      questionnaires. The outcome variables were participants' caries (mean DMFT) and
      periodontal disease experience (moderate or severe periodontal disease as defined
      by the Centre for Disease Control), with height as an explanatory variable.
      Antecedent anthropometric, socio-demographic, sugar consumption frequency, dental
      behaviour and substance use variables were used as possible confounders. Linear
      regression was used in the analysis of caries experience, while adjusted
      prevalence ratios were used for prevalence of moderate or severe periodontal
      disease. RESULTS: Higher DMFT was found among participants in the shortest
      tertile (B=1.02, 95% CI=0.02-2.02) and those who consumed sweets every day or a
      few days a week (B=1.08, 95% CI=0.11-2.05), while lower DMFT was found among
      those owning a toothbrush (B=0.80, 95% CI=-0.22-1.82). Periodontal disease was
      positively associated with the shortest tertile (adjusted PR=1.39, 95% CI=0.96
      1.82) and negatively associated with toothbrush ownership (adjusted PR=0.50, 95%
      CI=0.34-0.66). CONCLUSION: The hypothesis that shorter participants in wave-3 of
      the ABC study would have higher levels of caries and periodontal disease was
      confirmed.

PMID- 23550510
TI  - Inhibition mechanisms of Zn precipitation on aluminum oxide by glyphosate: a 31P
      NMR and Zn EXAFS study.
AB  - In this research, the effects of glyphosate (GPS) on Zn sorption/precipitation on
      gamma-alumina were investigated using a batch technique, Zn K-edge EXAFS, and
      (31)P NMR spectroscopy. The EXAFS analysis revealed that, in the absence of
      glyphosate, Zn adsorbed on the aluminum oxide surface mainly as bidentate
      mononuclear surface complexes at pH 5.5, whereas Zn-Al layered double hydroxide
      (LDH) precipitates formed at pH 8.0. In the presence of glyphosate, the EXAFS
      spectra of Zn sorption samples at pH 5.5 and 8.0 were very similar, both of which
      demonstrated that Zn did not directly bind to the mineral surface but bonded with
      the carboxyl group of glyphosate. Formation of gamma-alumina-GPS-Zn ternary
      surface complexes was further suggested by (31)P solid state NMR data which
      indicated the glyphosate binds to gamma-alumina via a phosphonate group, bridging
      the mineral surface and Zn. Additionally, we showed the sequence of additional
      glyphosate and Zn can influence the sorption mechanism. At pH 8, Zn-Al LDH
      precipitates formed if Zn was added first, and no precipitates formed if
      glyphosate was added first or simultaneously with Zn. In contrast, at pH 5.5,
      only gamma-alumina-GPS-Zn ternary surface complexes formed regardless of whether
      glyphosate or Zn was added first or both were added simultaneously.

PMID- 23550511
TI  - Controlled aerobic exercise training reduces resting blood pressure in sedentary
      older adults.
AB  - The results of existing controlled clinical trials were synthesized to determine
      effects of aerobic exercise training on resting systolic (SBP) and diastolic
      blood pressure (DBP) among previously sedentary older adults, to quantify the
      magnitude of observed changes, and to examine the influence of the associated
      interventional variables on these changes. Studies were identified via a
      systematic computer database search, hand searching, and cross-referencing of
      previously located articles. All potentially eligible articles were carefully
      reviewed and examined with the established inclusion criteria. Twenty-three
      studies, representing a total of 1226 older subjects, were included in the final
      analysis. Robust statistically significant effects were found in terms of the
      pooled standardized effect size of - 0.33 +/- 0.06 (p < 0.0001) in SBP and - 0.39
      +/- 0.09 (p < 0.0001) in DBP. When compared with the control group, net decreases
      in both SBP (- 5.39 +/- 1.21 mmHg, p < 0.0001) and DBP (-3.68 +/- 0.83 mmHg, p <
      0.0001) were observed in older exercisers, representing a 3.9% and a 4.5%
      reduction, respectively. This meta-analytic study provides robust quantitative
      data to support the efficacy and effectiveness of controlled endurance exercise
      training in decreasing resting SBP and DBP among previously sedentary older
      adults.

PMID- 23550512
TI  - Microfluidic space-domain time-resolved emission spectroscopy of terbium(III) and
      europium(III) chelates with pyridine-2,6-dicarboxylate.
AB  - This article describes the utilization of laminar microflows for time-resolved
      emission measurements with steady-state excitation and detection. Passing a
      laminar flow through a short illuminated section of a microchannel provided a
      means for pulsed-like photoexcitation of the moieties carried by the fluid.
      Imaging the microchannel flows carrying thus photoexcited chelates of lanthanide
      ions allowed us to extract their excited-state lifetimes from the spatial
      distribution of the changes in the emission intensity. The lifetime values
      obtained using this space-domain approach agreed well with the lifetimes from
      time-domain measurements. This validated space-domain microfluidic approach
      reveals a means for miniaturization of time-resolved emission spectroscopy. 

PMID- 23550513
TI  - Directional Raman scattering from single molecules in the feed gaps of optical
      antennas.
AB  - Controlling light from single emitters is an overarching theme of nano-optics.
      Antennas are routinely used to modify the angular emission patterns of radio wave
      sources. "Optical antennas" translate these principles to visible and infrared
      wavelengths and have been recently used to modify fluorescence from single
      quantum dots and single molecules. Understanding the properties of single
      molecules, however, would be advanced were one able to observe their vibrational
      spectra through Raman scattering in a very reproducible manner but it is a hugely
      challenging task, as Raman scattering cross sections are very weak. Here we
      measure for the first time the highly directional emission patterns of Raman
      scattering from single molecules in the feed gaps of optical antennas fabricated
      on a chip. More than a thousand single molecule events are observed, revealing
      that an unprecedented near-unity fraction of optical antennas have single
      molecule sensitivity.

PMID- 23550514
TI  - Anaphylaxis after the injection of buprenorphine.
AB  - Cause of death rulings in cases when the concentration of a drug or drugs is
      higher than observed following therapeutic use are generally straightforward
      "drug deaths." However, when toxicology testing identifies drug concentrations
      consistent with therapeutic use or detects no drugs at all, then the cause of
      death determination is more complicated. Given the rapidity and protean
      manifestations of anaphylaxis, it should be considered in deaths where no other
      cause of death is apparent in a suspected drug death. This article reports two
      cases where an anaphylactic reaction was observed following either the actual or
      alleged use of therapeutic formulations of buprenorphine intravenously. 

PMID- 23550515
TI  - Characterization of genes for a putative hydroxycinnamoyl-coenzyme A quinate
      transferase and p-coumarate 3'-hydroxylase and chlorogenic acid accumulation in
      tartary buckwheat.
AB  - Tartary buckwheat ( Fagopyrum tataricum Gaertn.) contains a high level of
      flavonoid compounds, which have beneficial and pharmacological effects on health.
      In this study, we isolated full-length cDNAs encoding hydroxycinnamoyl-coenzyme A
      quinate hydroxycinnamoyltransferase (HQT) and p-coumarate 3'-hydroxylase (C3H),
      which are involved in chlorogenic acid (CGA) biosynthesis. We examined the
      expression levels of HQT and C3H using real-time RT-PCR in different organs and
      sprouts of two tartary buckwheat cultivars (Hokkai T8 and T10) and analyzed CGA
      content using high-performance liquid chromatography. Among the organs, the
      flowers in both cultivars showed the highest levels of CGA. We concluded that the
      expression pattern of FtHQT and FtC3H did not match the accumulation pattern of
      CGA in different organs of T8 and T10 cultivars. Gene expression and CGA content
      varied between the cultivars. We presume that FtHQT and FtC3H levels might be
      controlled by multiple metabolic pathways in different organs of tartary
      buckwheat. Probably, FtC3H might have a greater effect on CGA biosynthesis than
      FtHQT. Our results will be helpful for a greater understanding of CGA
      biosynthesis in tartary buckwheat. 

PMID- 23550516
TI  - Disease progression and patient survival are significantly influenced by BRAF
      protein expression in primary melanoma.
AB  - BACKGROUND: Mutation of BRAF is a prevalent event in melanoma. Despite much
      attention to the role of BRAF mutation in melanoma, the status of BRAF protein
      expression and its significance in melanoma progression are unknown. OBJECTIVES:
      We investigated the BRAF expression level in different stages of melanocytic
      lesions and evaluated its correlation with clinicopathological features and
      patient survival. METHODS: Using tissue microarray, BRAF expression and its
      correlation with patient outcome was evaluated in 49 naevi samples and 370
      patients with melanoma. We also evaluated the correlation of BRAF protein
      expression and V600E mutation using direct sequencing. RESULTS: Compared with
      naevi samples, BRAF expression was remarkably increased in primary melanomas and
      further increased in metastatic melanomas (P = 1.8 * 10(-11) ). High BRAF
      expression was significantly correlated with thicker tumours, ulceration and
      higher American Joint Committee on Cancer stages (P = 1.5 * 10(-7) , 1.5 * 10(-5)
      and 3.6 * 10(-13) , respectively). In cases of primary melanoma, patients with
      high BRAF expression had significantly worse overall (P = 0.009) and disease
      specific 5-year survival (P = 0.007). While there was a trend for higher
      prevalence of BRAF V600E mutation in patients with high BRAF protein expression,
      no significant correlation was observed between protein expression and BRAF
      mutation. Furthermore, univariate Cox regression analysis confirmed high BRAF
      protein expression as a strong risk factor for poor patient survival in primary
      melanoma [hazard ratio (HR) 2.08 for overall survival; HR 2.39 for disease
      specific survival]. CONCLUSIONS: Our data demonstrate that BRAF protein
      expression is significantly increased during melanoma progression. In addition,
      we revealed a novel prognostic value for BRAF protein expression in primary
      melanoma as it is significantly correlated with poor patient survival.

PMID- 23550517
TI  - Workforce skill mix: modelling the potential for dental therapists in state
      funded primary dental care.
AB  - BACKGROUND: South Central Strategic Health Authority [SHA], with a population of
      four million, is one of 10 regions of England with responsibility for workforce
      planning. AIM: To explore future scenarios for the use of the skill mix within
      the dental team to inform the commissioning of dental therapy training. METHOD:
      Data on population demography, oral health needs and demands, dental workforce,
      activity and dental utilisation were used to create demand (needs-informed) and
      supply models. Population trends and changing oral health needs and dental
      service uptake were included in the demand model. Linear programming was used to
      obtain the optimal make-up of the dental team. Based on the optimal scenario,
      workforce volumes and costs were examined across a range of scenarios up to 2013.
      RESULTS: Baseline levels of dental therapists were low and estimated as only
      achieving 10-20% of the current potential job competency. The optimal exploratory
      scenario in terms of costs and volume of staff was based on dental therapists
      working full time and providing 70% of routine care that is within their current
      job competency; this scenario required 483 therapists by 2013, a figure that
      appeared achievable. Increasing the level of job competency provided by
      therapists revealed potentially higher benefits in terms of reduced cost and
      requiring fewer dentists. CONCLUSION: The findings suggest that dental therapists
      can play a more significant role in the provision of primary dental care, both
      currently and in future; they also highlight the need for health services to
      routinely collect data that can inform workforce analysis and planning.

PMID- 23550518
TI  - Leprosy and its dental management guidelines.
AB  - OBJECTIVES: Leprosy is a chronic, non-fatal disease caused by Mycobacterium
      leprae. It can cause cutaneous lesions, peripheral nerve lesions and orofacial
      manifestations, including destruction of the alveolar premaxillary process
      associated with loss of the maxillary incisors. The aims of this study were to
      assess orofacial manifestations of disease in patients attending the Bombay
      Leprosy Project clinics and develop clinical guidelines for dentists. MATERIALS
      AND METHODS: A cross-sectional questionnaire based study was administered to 43
      diagnosed leprosy patients. This included questions on perceived oral health
      status and oral hygiene habits. An extra-oral and intra-oral examination was also
      performed. RESULTS: Eighty-four per cent of patients were male with a mean age of
      35.9 years. Forty-nine per cent had extra-oral cutaneous lesions. Twenty-eight
      per cent had intra-oral lesions including hyperpigmented patches. Twenty-one per
      cent had cranial nerve involvement and the trigeminal nerve was most commonly
      affected. CONCLUSIONS: From this data a clinical dental pathway protocol for
      managing patients with leprosy was developed. It highlights dental issues when
      managing leprosy patients. Nerve involvement may mean patients are unable to give
      an accurate account of their symptoms. Special tests should include cranial nerve
      examination and swabs of intra-oral ulcers. Low rates of infectivity means that
      normal infection control measures can be taken when treating these patients.

PMID- 23550519
TI  - Prevalence of dental caries in 5-year-old Greek children and the use of dental
      services: evaluation of socioeconomic, behavioural factors and living conditions.
AB  - OBJECTIVES: To assess dental caries and use of dental services experience in 5
      year-old children attending public kindergartens in Attica, Greece and to examine
      the influence of certain socioeconomic factors and living conditions as well as
      dental behaviours and attitudes. METHODS: In this cross-sectional study, a random
      and stratified sample of 605 Greek children was examined using decayed, missing,
      filled tooth surfaces and simplified debris indices. The use of dental services
      was measured by children's dental visits (any dental visit up to the age of 5
      years). Care Index was also calculated. Risk indicators were assessed by a
      questionnaire. Zero-inflated Poisson and Logistic Regression Analysis were
      generated to test statistical significant associations. RESULTS: The prevalence
      of dental caries was 16.5%. Care Index was 32% and dental visits were reported
      for the 84% of the children. Medium Socio-Economic Level (SEL) was associated
      with no detectable caries. High SEL was related to decreased decayed, missing,
      filled teeth values, while female gender and rented houses had the opposite
      effect. The age of the mother (35-39 years) and the higher SEL were related to
      higher levels of dental services use. CONCLUSIONS: It is suggested that there are
      differences in the experience of dental caries and use of dental services among
      preschool children in Attica, which are related to demographic, socioeconomic
      factors and living conditions. Dental public polices should focus on groups with
      specific characteristics in order to improve oral health levels of disease
      susceptible populations.

PMID- 23550520
TI  - Assessing dental students' knowledge of oral cancer in the United Arab Emirates.
AB  - OBJECTIVE: The purpose of this study was to assess the knowledge of future
      dentists of the United Arab Emirates on risk and non-risk factors for oral
      cancers and correlate it with their own tobacco use, whether they assess their
      patients' tobacco use and their opinion about the relation of oral cancer and
      smokeless tobacco use. METHODS: A total of 270, first- to fifth-year
      undergraduate dental students who consented to participate in the study filled in
      a questionnaire enquiring about their knowledge of oral cancer risk factors. A
      score of oral cancer risk factor knowledge was calculated for each participant
      based on their correct answers. RESULTS: Eighty-three per cent of participants
      identified the use of tobacco as a risk factor for oral cancer, 52% identified
      old age, 45.6% knew about low consumption of fruits and vegetables and 74.4% of
      students could correctly identify use of alcohol as a risk factor for oral
      cancer. A significant association was found between being a current and previous
      tobacco user and having low knowledge of risk factors score (P = 0.015). No
      significant associations were found between the year of study in the dental
      college, gender, nationality and knowledge of oral cancer risk factor scores.
      CONCLUSION: This study showed an apparent lack of knowledge of oral cancer risk
      factors among dental students that may later result in a deficiency in
      integrating optimal oral cancer diagnostic procedures in their practices. There
      is an urgent need to enhance the oral cancer curricula in oral cancer education
      and clinical training in oral cancer prevention and examination for dental
      students.

PMID- 23550521
TI  - The concepts of minimally invasive dentistry and its impact on clinical practice:
      a survey with a group of Brazilian professionals.
AB  - This cross-sectional study aimed to assess the knowledge and attitudes of 123
      Brazilian dentists in relation to the concepts and practice of minimally invasive
      dentistry (MID). Data were collected through a questionnaire developed and
      validated by experts. Statistical analysis was performed using an spss program
      and Pearson's chi-square test. Most participants had up to 10 years experience
      after graduation (69.9%), were specialised (60.2%) and worked in public and
      private service (43.1%). Regarding current concepts of dental caries, 87.0% were
      unaware and 65.9% answered that the treatment involves only the restorative
      phase. In relation to caries lesion arrest, 39.8% replied that it depended on the
      total removal of carious tissue. Most of them were aware of MID procedures
      (82.1%) but 49.6% did not follow them in daily practice. From these participants,
      48.4% did not believe in the technique or did not know how to perform it.
      Decisions on partial or total removal of carious dentine, behaviour in relation
      to the procedures (permanent or temporary) and the practice of MID were not
      influenced by how long since the professionals had graduated or become
      specialised. It can be concluded that scientific evidence reaches most of the
      professionals, but does not benefit all patients, as many practitioners still
      follow the principles of total removal of carious tissue. Teaching should include
      making professionals fully aware of the carious process and encourage them to
      fully adopt the techniques and attitudes of MID.

PMID- 23550522
TI  - Emerging trends in dental specialty choice in Nigeria.
AB  - Asymmetry in the distribution of dental specialists in Nigeria has the potential
      to negatively affect dental education at all levels. There is a dearth in
      Nigerian studies on the trends of influencing factors on the choice of dental
      specialty in Nigeria. Past efforts have not resulted in policy change thus
      necessitating the current study. One hundred and twelve (51 male, 61 female)
      Nigerian dental graduates aged 23-55 years with a mean age of 35.21 +/- 8.21
      years completed self-administered questionnaires to assess the impact of 16
      influencing factors on their choice of dental specialty. The graduation period of
      respondents, which ranged between 0 and 30 years was recorded into three decades
      and cross-tabulated against 16 influencing factors to assess their relative
      impact on specialty choice. Diagnostic challenge, predictable work hours and
      patient type appeared to have maintained a consistent popularity while affluence
      and income, although less popular influences three decades ago are becoming
      increasingly relevant while length of programme, prestige and level of crowding
      exerted less influence on choice of specialty than other factors. The potential
      influence of incentives such as career counselling and grants for overseas
      training to encourage enrollment in less popular programmes was assessed based on
      recommendations from previous studies. However, these measures appeared to be
      unpopular among Nigerian dental graduates. Diagnostic challenges and predictable
      work hours remain popular as influencing factors on choice of dental specialty
      among Nigerian dental graduates. Affluence and income, although previously
      unpopular are now gaining popularity among Nigerian dental graduates.

PMID- 23550523
TI  - Comparison of laser fluorescence devices for detection of caries in primary
      teeth.
AB  - The aim of this in vivo study was to evaluate the performance of fluorescence
      based devices in detecting occlusal caries lesions in primary molars compared
      with conventional methods. Two examiners assessed 44 occlusal surfaces of first
      and second primary molars in 20 patients using two fluorescence devices:
      DIAGNOdent (LF) and DIAGNOdent pen (LFpen). Teeth were also assessed by visual
      examination and bitewing radiograph. Histological examination served as the gold
      standard after extraction. By using the McNemar test, the sensitivity,
      specificity, accuracy, and area under the receiver operating curve were
      calculated as outer enamel (D1), inner enamel (D2) and dentine caries (D3) lesion
      thresholds. The intra- and inter-examiner reproducibility were calculated using
      the Cohen's unweighted kappa statistics. At the D1 threshold, the LFpen
      sensitivity was statistically higher than LF and radiographic examination (P <
      0.001), whereas there was no statistically significant difference among the
      groups at the D2 and D3 thresholds (P > 0.05). All methods demonstrated the
      highest sensitivity values at D3. At the D1 and D2 thresholds, there were no
      significant differences between the LFpen specificity and the other methods. All
      methods presented similar performance in detecting all lesions considering the
      area under the receiver operating curve. The LFpen showed better performance than
      LF. Furthermore, visual examination and the LFpen device seem to be sufficient
      for detection of occlusal caries in primary molars.

PMID- 23550524
TI  - Dental therapists/hygienists working in remote-rural primary care: a structured
      review of effectiveness, efficiency, sustainability, acceptability and
      affordability.
AB  - AIM: To examine the use of dental therapist/hygienists to provide primary dental
      treatment in remote-rural areas with regard to their effectiveness, efficiency,
      sustainability, acceptability and costs (affordability). METHOD: The structured
      literature review of studies indexed in Medline, Embase and CinAHL was conducted
      using search terms relevant to 'dental therapists' and 'remote-rural'. Remote
      rural was defined as 'those (individuals) with a greater than 30-minute drive
      time to the nearest settlement with a population of greater than 10,000'.
      RESULTS: From 1,175 publications screened, 21 studies from 19 publications were
      initially included. Only seven studies were included that explicitly focused on
      remote-rural areas. Four were surveys and three were qualitative studies. All of
      the included studies were reported within the last 7 years. The methodological
      quality of the surveys varied, particularly with regard to their response rates.
      All three of the qualitative studies were assessed as potentially weak
      methodologies. Regarding the research question, none of the studies included
      provided data relevant to understanding efficiency, cost issues or the
      acceptability of dental therapists. The available empirical evidence contained
      only indirect indicators about the sustainability of dental therapy in rural
      areas. CONCLUSIONS: The available data indicates that dental therapist/hygienists
      have suitable skills and could constitute a valuable asset to meet the dental
      demands in remote-rural areas. However, the evidence base is limited and of a
      poor quality. There is a need to put in place 'well-designed interventions with
      robust evaluation to examine cost-effectiveness and benefits to patients and the
      health workforce'.

PMID- 23550525
TI  - Strategies for early detection of chronic Q-fever: a systematic review.
AB  - BACKGROUND: Chronic Q-fever, a condition with high morbidity and mortality, may
      develop after an acute infection with Coxiella burnetii (acute Q-fever). Several
      strategies have been suggested for early detection of chronic Q-fever, focusing
      on follow-up of known acute Q-fever patients and detection of asymptomatic or
      unknown chronic infections. As there is no international standard or consensus,
      the aims of this study were to summarise the available literature and assess the
      evidence for different follow-up and screening strategies. DESIGN: We conducted a
      systematic review by searching PubMed and Embase. Twenty articles were included,
      of which fourteen only provided information on follow-up of known acute Q-fever
      cases, four presented data on identification of previously unknown C. burnetii
      infections, and two had information on both topics. RESULTS: The conversion rate
      of acute to chronic Q-fever ranged from 0 to 5.0%. Most studies advised
      serological follow-up of acute Q-fever patients, but without consistent advice on
      optimum timing and duration. The recommendation to use echocardiography for all
      acute Q-fever patients to detect valvular damage remains controversial. Screening
      of high-risk patients in an outbreak setting is advised by studies investigating
      such strategy. CONCLUSIONS: There is sufficient evidence to support serological
      follow-up of all known acute Q-fever patients at least once during the first year
      following the acute infection, and more frequently in patients with known risk
      factors for chronic disease, such as heart valve- or vascular prosthesis.
      Screening of risk groups should be considered in outbreaks of Q-fever.

PMID- 23550526
TI  - New Beginnings for mothers and babies in prison: a cluster randomized controlled
      trial.
AB  - Mothers in prison represent a high-risk parenting population. New Beginnings is
      an attachment-based group intervention designed specifically for mothers and
      babies in prison. This cluster randomized trial examined the outcomes for 88
      mothers and babies participating in the New Beginnings program and 75 dyads
      residing in prisons where the intervention did not take place. Outcomes were
      measured in terms of parental reflective functioning, the quality of parent
      infant interaction, maternal depression, and maternal representations. Mothers in
      the control group deteriorated in their level of reflective functioning and
      behavioral interaction with their babies over time, whereas the mothers in the
      intervention group did not. There were no significant group effects on levels of
      maternal depression or mothers' self-reported representations of their babies
      over time. An attachment-based intervention may mitigate some of the risks to the
      quality of the parent-infant relationship for these dyads. 

PMID- 23550527
TI  - Deletion of the Phytophthora sojae avirulence gene Avr1d causes gain of virulence
      on Rps1d.
AB  - Phytophthora sojae is an oomycete and a pathogen of soybean that causes root rot.
      During infection P. sojae delivers effector proteins into host cells to foster
      disease. However, effector-triggered immunity (ETI) results when pathogen factors
      are recognized by host resistance (R) proteins. We have now identified the P.
      sojae Avr1d gene, which encodes a predicted effector protein with the amino acid
      motif Arg-X-Leu-Arg (RXLR). Genetic mapping of 16 different P. sojae isolates and
      of a segregating F2 population of 40 individuals shows that the predicted RXLR
      effector gene Avh6 precisely cosegregates with the Avr1d phenotype. Transient
      expression assays confirm that Avr1d triggers cell death specifically in Rps1d
      soybean plants. The Avr1d gene is present in P. sojae strains that are avirulent
      on Rps1d, whereas the gene is deleted from the genome of virulent strains. Two
      sequence variants of the Avr1d gene encoding different protein products occur in
      P. sojae strains, but both are recognized by Rps1d and cause ETI. Liposome
      binding assays show that Avr1d has affinity for phosphatidylinositol 4-phosphate
      and that binding can be disrupted by mutation of lysine residues in the carboxy
      terminal effector domain of the protein. The identification of Avr1d aids
      pathogen diagnostics and soybean cultivar development. 

PMID- 23550528
TI  - Microbe-independent entry of oomycete RxLR effectors and fungal RxLR-like
      effectors into plant and animal cells is specific and reproducible.
AB  - A wide diversity of pathogens and mutualists of plant and animal hosts, including
      oomycetes and fungi, produce effector proteins that enter the cytoplasm of host
      cells. A major question has been whether or not entry by these effectors can
      occur independently of the microbe or requires machinery provided by the microbe.
      Numerous publications have documented that oomycete RxLR effectors and fungal
      RxLR-like effectors can enter plant and animal cells independent of the microbe.
      A recent reexamination of whether the RxLR domain of oomycete RxLR effectors is
      sufficient for microbe-independent entry into host cells concluded that the RxLR
      domains of Phytophthora infestans Avr3a and of P. sojae Avr1b alone are NOT
      sufficient to enable microbe-independent entry of proteins into host and nonhost
      plant and animal cells. Here, we present new, more detailed data that
      unambiguously demonstrate that the RxLR domain of Avr1b does show efficient and
      specific entry into soybean root cells and also into wheat leaf cells, at levels
      well above background nonspecific entry. We also summarize host cell entry
      experiments with a wide diversity of oomycete and fungal effectors with RxLR or
      RxLR-like motifs that have been independently carried out by the seven different
      labs that coauthored this letter. Finally we discuss possible technical reasons
      why specific cell entry may have been not detected by Wawra et al. (2013).

PMID- 23550529
TI  - Functional characterization of two clusters of Brachypodium distachyon UDP
      glycosyltransferases encoding putative deoxynivalenol detoxification genes.
AB  - Plant small-molecule UDP-glycosyltransferases (UGT) glycosylate a vast number of
      endogenous substances but also act in detoxification of metabolites produced by
      plant-pathogenic microorganisms. The ability to inactivate the Fusarium
      graminearum mycotoxin deoxynivalenol (DON) into DON-3-O-glucoside is crucial for
      resistance of cereals. We analyzed the UGT gene family of the monocot model
      species Brachypodium distachyon and functionally characterized two gene clusters
      containing putative orthologs of previously identified DON-detoxification genes
      from Arabidopsis thaliana and barley. Analysis of transcription showed that UGT
      encoded in both clusters are highly inducible by DON and expressed at much higher
      levels upon infection with a wild-type DON-producing F. graminearum strain
      compared with infection with a mutant deficient in DON production. Expression of
      these genes in a toxin-sensitive strain of Saccharomyces cerevisiae revealed that
      only two B. distachyon UGT encoded by members of a cluster of six genes
      homologous to the DON-inactivating barley HvUGT13248 were able to convert DON
      into DON-3-O-glucoside. Also, a single copy gene from Sorghum bicolor orthologous
      to this cluster and one of three putative orthologs of rice exhibit this ability.
      Seemingly, the UGT genes undergo rapid evolution and changes in copy number,
      making it difficult to identify orthologs with conserved substrate specificity.

PMID- 23550530
TI  - SRNAome parsing yields insights into tomato fruit ripening control.
AB  - Small RNAs have emerged as critical regulators in the expression and function of
      eukaryotic genomes at the post-transcriptional level. To elucidate the functions
      of microRNA (miRNAs) and endogenous small-interfering RNAs (siRNAs) in tomato
      fruit ripening process, the deep sequencing and bioinformatics methods were
      combined to parse the small RNAs landscape in three fruit-ripening stages (mature
      green, breaker and red-ripe) on a whole genome. Two species-specific miRNAs and
      two members of TAS3 family were identified, 590 putative phased small RNAs and
      125 cis-natural antisense (nat-siRNAs) were also found in our results which
      enriched the tomato small RNAs repository and all of them showed differential
      expression patterns during fruit ripening. A large amount of the targets of the
      small RNAs were predicted to be involved in fruit ripening and ethylene pathway.
      Furthermore, the promoters of the conserved and novel miRNAs were found to
      contain the conserved motifs of TATA-box and CT microsatellites which were also
      found in Arabidopsis and rice, and several species-specific motifs were found in
      parallel. 

PMID- 23550531
TI  - Impact of micronised purified flavonoid fraction on increased malondialdehyde and
      decreased metalloproteinase-2 and metalloproteinase-9 levels in varicocele:
      outcome of an experimentally induced varicocele.
AB  - To analyse the levels of an indirect marker of ROS-induced lipid peroxidation
      [i.e. malondialdehyde (MDA)] in both testes and the levels of matrix
      metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and matrix
      metalloproteinase inhibitor-1 (TIMP-1) in the left testis after induction of
      varicocele and investigated the impact of micronised purified flavonoid fraction
      (MPFF) on these markers. Forty-nine adolescent (6-week-old) male Wistar rats were
      included in this study. The rats were divided into seven groups as follows:Group
      1, control; Group-2, sham; Group-3, left varicocele-induced; Group-4, varicocele
      + varicocelectomy + MPFF-treated (for 4 weeks); Group-5, varicocele + MPFF
      treated (for 8 weeks); Group-6, varicocele-induced and 4 weeks later, MPFF
      treated (for 4 weeks); and Group-7, varicocele + varicocelectomy. MDA was
      measured in the tissues of both testes using the thiobarbituric acid reactivity
      method. The ELISA method was used for the quantification of MMP-2, MMP-9 and TIMP
      1 in the left testicular tissue. The levels of MDA were significantly higher in
      the varicocele group than in the other groups. The MDA levels in the left
      testicular tissues of Group-7 were significantly higher than those of Group 4 (P
      = 0.03). In the varicocele group, the MMP-2 and MMP-9 levels decreased, whereas
      the levels of TIMP-1 increased. The tissue levels of MMP-2 in Groups 4, 5 and 7
      were significantly higher than those in Group 1 (P < 0.05). 

PMID- 23550533
TI  - Predictors of neonatal outcomes amongst a methadone- and/or heroin-dependent
      population referred to a multidisciplinary Perinatal and Family Drug Health
      Service.
AB  - BACKGROUND AND AIMS: Although methadone maintenance therapy is the standard of
      care for opioid-dependent pregnant women, there exists controversy over the
      benefits and side effects of treatment to the neonate. Our aim was to document
      predictors of neonatal outcomes within an opioid-using population, with
      particular reference to methadone treatment in the context of continued heroin
      use. METHODS: Analysis was performed on a cohort of 183 opioid-using pregnant
      women seen by the Sydney South West Area Health Service between 2004 and 2007 and
      between 2009 and 2011. Neonatal outcomes were analysed according to maternal
      opioid use: methadone only, methadone and heroin, or heroin only. Logistic
      regression was used to examine independent predictors of neonatal outcomes.
      RESULTS: No difference in the frequency of low birth weight neonates or the rate
      of prematurity was found between the methadone-only, methadone-and-heroin and
      heroin-only groups (P = 0.30; P = 0.42). Methadone treatment was not found to
      increase the treatment requirement for neonatal abstinence syndrome compared with
      those using heroin only (P = 0.91). Women using methadone only were more likely
      to retain custody of their child at hospital discharge than women using methadone
      and heroin and heroin only (80.4, 59.0, 40.0%; P < 0.001). CONCLUSIONS: Methadone
      treatment was beneficial in predicting the discharge custody status of the
      neonate. Engagement with antenatal care was found to reduce the likelihood of
      preterm birth and to be independently associated with the neonate being
      discharged in the care of the mother. Women who continue to use heroin should not
      be denied methadone treatment for fear of worse neonatal outcomes.

PMID- 23550534
TI  - Effectiveness of eye movement desensitization and reprocessing treatment in post
      traumatic stress disorder after childbirth: a randomized controlled trial
      protocol.

PMID- 23550535
TI  - Diversity of forensic rove beetles (Coleoptera, Staphylinidae) associated with
      decaying pig carcass in a forest biotope.
AB  - Most forensic studies are focused on Diptera pattern colonization while
      neglecting Coleoptera succession. So far, little information is available on the
      postmortem colonization by beetles and the decomposition process they initiate
      under temperate biogeoclimatic countries. These beetles have, however, been
      referred to as being part of the entomofaunal colonization of a dead body.
      Forensic entomologists need increased databases detailing the distribution,
      ecology, and phenology of necrophagous insects, including staphylinids
      (Coleoptera, Staphylinidae). While pig carcasses are commonly used in forensic
      entomology studies to surrogate human decomposition and to investigate the
      entomofaunal succession, very few works have been conducted in Europe on large
      carcasses. Our work reports the monitoring of the presence of adult rove beetles
      (Coleoptera, Staphylinidae) on decaying pig carcasses in a forest biotope during
      four seasons (spring, summer, fall, and winter). A total of 23 genera comprising
      60 species of rove beetles were collected from pig carcasses.

PMID- 23550536
TI  - Systematic review: the quality of the scientific evidence and conflicts of
      interest in international inflammatory bowel disease practice guidelines.
AB  - BACKGROUND: Guidelines published by the international gastroenterology societies
      establish standards of care and seek to improve patient outcomes. AIM: We
      examined inflammatory bowel disease guidelines (IBD) for quality of evidence,
      methods of grading evidence and conflicts of interest (COI). METHODS: All 182
      guidelines published by the American College of Gastroenterology, American
      Gastroenterological Association, British Society of Gastroenterology, Canadian
      Association of Gastroenterology, Crohn's and Colitis Foundation of America and
      European Crohn's and Colitis Organisation as of 27 September 2012 were reviewed.
      Nineteen IBD guidelines were found. RESULTS: Eighty-nine per cent (n = 17/19) of
      the guidelines graded the levels of evidence using seven different systems. Of
      the 1070 recommendations reviewed, 23% (n = 249) cited level A evidence; 28% (n =
      302) level B; 36% (n = 383) level C and 13% (n = 136) level D. The mean age of
      the guidelines was 4.2 years. In addition, 61% (n = 11/19) of the guidelines
      failed to comment on COI. All eight articles commenting on COI had conflicts with
      81% (n = 92/113) of authors reported an average 11.7 COI. Lastly, there were
      variations in the recommendations between societies. CONCLUSIONS: Nearly half the
      IBD guideline recommendations are based on expert opinion or no evidence.
      Majority of the guidelines fail to disclose any COI, and when commenting, all
      have numerous COI. Furthermore, the guidelines are not updated frequently and
      there is a lack of consensus between societal guidelines. This study highlights
      the critical need to centralize and redesign the guidelines development process.

PMID- 23550537
TI  - Eccentricity dependent changes of density, spacing and packing arrangement of
      parafoveal cones.
AB  - PURPOSE: To investigate the distribution of cone density and spacing as well as
      the preferred packing arrangement of the cone mosaic as a function of retinal
      eccentricity. METHODS: An adaptive optics retinal camera (rtx1, www.imagine
      eyes.com) was used to obtain images of the parafoveal cone mosaic in nineteen
      healthy volunteers. Cone density and spacing were estimated for each subject
      (both eyes) using a sampling window of 80 * 80 pixels, at 250-, 450-, 650- and
      1100-MUm eccentricities from the fovea along the nasal and temporal retina of
      both eyes. The inter-subject and intra-subject variation of cone density and
      spacing were calculated via Coefficient of Variation (CoV). Cone packing
      arrangement was assessed using Voronoi analysis; calculations were done over 1024
      * 128 pixels image sections of the cone mosaic across the horizontal meridian
      from 200- to 1050-MUm eccentricities. RESULTS: The inter-subject variation of
      parafoveal cone density ranged between 10% and 15% (p < 0.001) and the intra
      subject variation of cone density was lower than 8% in all subjects, except for
      two. The cone spacing values showed a moderate inter-subject (CoV<7%; p < 0.001)
      and a low intra-subject variation (CoV<4% in all subjects, except for two cases).
      In the parafoveal region, 40-50% of cones were hexagonally arranged; the
      percentage of non-hexagonal Voronoi tiles increased at greater eccentricities.
      CONCLUSION: The use of multiple and complementary metric descriptors allows for a
      more detailed description of packing distribution and preferred arrangement of
      cone photoreceptors across the parafoveal retina.

PMID- 23550538
TI  - Comparison of irrigant penetration up to working length and into simulated
      lateral canals using various irrigating techniques.
AB  - AIM: To evaluate the effect of an apical negative pressure system, a passive
      ultrasonic irrigation system and a combination of both apical negative pressure
      and passive ultrasonic irrigation on the penetration of the irrigating contrast
      solution (ICS) up to working length and into simulated lateral canals.
      METHODOLOGY: The root canals of 64 single-rooted teeth were instrumented using
      the ProTaper rotary system. In each sample, three simulated lateral canals were
      created at 2, 4 and 6 mm levels from the root apex using a 06-size C+ file
      (Dentsply Maillefer, Ballaigues, Switzerland). Samples were randomly assigned
      into 4 experimental groups (n = 16): group I - conventional needle irrigation,
      group II - passive ultrasonic irrigation, group III - apical negative irrigation
      system and group IV - combination of passive ultrasonic irrigation and apical
      negative pressure irrigation system. To examine irrigating solution penetration,
      Indian ink was mixed with 5.25% NaOCl and delivered into the root canals. Samples
      were then assessed by direct observation of the images taken using Canon EOS
      rebel T3. The depth of penetration of ICS up to the working length and into the
      simulated lateral canals was analysed using chi-squared tests. RESULTS: The
      combination (ANP and PUI) and ANP group had significantly deeper ICS penetration
      up to the working length (P < 0.001). The combination (ANP and PUI) and the PUI
      group exhibited significantly greater ICS penetration into lateral canals at the
      6 mm level (P < 0.001). At the 4 and 2 mm levels, the combination of ANP and PUI
      had significantly greater ICS penetration into the lateral canals than the other
      groups (P < 0.001). CONCLUSIONS: The combination of ANP and PUI was the only
      group able to achieve irrigating contrast solution penetration both up to the
      working length and into lateral canals.

PMID- 23550539
TI  - A novel armed oncolytic measles vaccine virus for the treatment of
      cholangiocarcinoma.
AB  - Cholangiocarcinoma (CC) is curable only in early stages by complete surgical
      resection. Thus, in advanced disease stages in which a complete removal of the
      tumor mass is no longer possible and palliative chemotherapy achieves only modest
      success, therapeutics employing new methods of action are desperately needed.
      Oncolytic viruses employed in clinical studies have been shown to spread
      preferentially in cancer cells. Beyond that, virotherapeutic cell killing can be
      enhanced by virus-based expression of suicide genes. We engineered a measles
      vaccine virus (MeV) vector expressing super cytosine deaminase (SCD), a fusion
      protein of yeast cytosine deaminase and uracil phosphoribosyltransferase, which
      converts the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) and
      subsequently to 5-fluorouridine-monophosphate. This novel vector was evaluated
      using three different human-derived CC cell lines. In vitro, all CC cell lines
      were found to be permissive to MeV infection. Partial blocking of MeV-mediated
      oncolysis could be overcome by employment of the SCD transgene together with
      administration of 5-FC. In vivo, intratumoral application of SCD-armed MeV
      together with a systemic 5-FC treatment showed a significant reduction in tumor
      size in a TFK-1 xenograft mouse model when compared with virus-only treatment. In
      a second animal experiment employing a HuCCT1 xenograft tumor model, an enhanced
      SCD-armed MeV vector, in which the SCD transgene was expressed from a different
      genomic position, led not only to reduced tumor volumes, but also to a
      significant survival benefit. On the basis of these encouraging preclinical data
      on employment of SCD-armed MeV for the virotherapeutic treatment of chemotherapy
      resistant CC, a clinical virotherapy trial is set up currently.

PMID- 23550540
TI  - Assessment of total hip arthroplasty by means of computed tomography 3D models
      and fracture risk evaluation.
AB  - Total hip arthroplasty (THA) can be achieved by using a cemented or noncemented
      prosthesis. Besides patient's age, weight, and other clinical signs, the
      evaluation of the quality of the bones is a crucial parameter on which orthopedic
      surgeons base the choice between cemented and noncemented THA. Although bone
      density generally decreases with age and a cemented THA is preferred for older
      subjects, the bone quality of a particular patient should be quantitatively
      evaluated. This study proposes a new method to quantitatively measure bone
      density and fracture risk by using 3D models extracted by a preoperative computed
      tomography (CT) scan of the patient. Also, the anatomical structure and
      compactness of the quadriceps muscle is computed to provide a more complete view.
      A spatial reconstruction of the tissues is obtained by means of CT image
      processing, then a detailed 3D model of bone mineral density of the femur is
      provided by including quantitative CT density information (CT must be
      precalibrated). A finite element analysis will provide a map of the strains
      around the proximal femur socket when solicited by typical stresses caused by an
      implant. The risk for structural failure due to press-fitting and compressive
      stress during noncemented THA surgery was estimated by calculating a bone
      fracture risk index (ratio between actual compressive stress and estimated
      failure stress of the bone). A clinical trial was carried out including 36
      volunteer patients (ages 22-77) who underwent unilateral THA surgery for the
      first time: 18 received a cemented implant and 18 received a noncemented implant.
      CT scans were acquired before surgery, immediately after, and after 12 months.
      Bone and quadriceps density results were higher in the healthy leg in about 80%
      of the cases. Bone and quadriceps density generally decrease with age but mineral
      density may vary significantly between patients. Preliminary results indicate the
      highest fracture risk at the calcar and the lowest at the intertrocanteric line,
      with some difference between patients. An analysis of the results suggest that
      this methodology can be a valid noninvasive decision support tool for THA
      planning; however, further analyses are needed to tune the technique and to allow
      clinical applications. Combination with gait analysis data is planned.

PMID- 23550541
TI  - A novel mutation in GJA1 causing oculodentodigital syndrome and primary
      lymphoedema in a three generation family.
AB  - Oculodentodigital syndrome (ODD; OMIM 164200) is a congenital condition with
      phenotypic features most commonly affecting the face, eyes, dentition and digits.
      The condition is caused by mutations in the GJA1 gene on chromosome 6. GJA1 codes
      for connexin 43, a gap junction protein important in providing cell to cell
      communication and is expressed in lymphatic valves. We present a patient with a
      clinical and molecular diagnosis of ODD and lower limb lymphoedema. Sanger
      sequencing of family members confirmed that the missense, p.K206R, GJA1 mutation
      segregated with the phenotype suggestive of causality. To our knowledge this
      association has not been reported previously. This is therefore the second
      connexin gene associated with a lymphoedema phenotype after the recent
      publication of GJC2 (connexin 47) as a cause of four limb lymphoedema. 

PMID- 23550543
TI  - Conjugated and immobilized photosensitizers for combating bacterial infections.
AB  - The technique of photosensitization for eradication of bacterial cells involves
      the use of molecules called photosesitizers (PSs) which generate reactive oxygen
      species (ROS) upon illumination with light of a suitable wavelength. ROS can
      oxidize biological molecules such as proteins, nucleic acids and lipids, which
      ultimately leads to bacterial cell death. Use of PS-conjugates and immobilized PS
      can lead to a reduction in the amount of a compound necessary for bacterial cell
      eradication. In addition, PS-conjugates for delivering photosensitizer molecules
      are more effective for clinical applications, since the photosensitizers are
      targeted directly to bacterial cells. This review reports studies and patents
      that demonstrate the possibility of increasing bacterial cells eradication by
      using specific and non-specific PS-conjugates such as: PS-antibiotic, PS
      polycation (including PS-poly-L-lysine and PS-polyethyleneimine), PS
      bacteriophage, PS-IgG and PS-siderophore. Studies and patents describing
      immobilized PS for drug delivery are also considered.

PMID- 23550544
TI  - Liposome-encapsulated photosensitizers against bacteria.
AB  - Photodynamic therapy (PDT), utilizing photosensitizers and light, has received
      considerable interests for its potential to treat microbial infections. The
      advantages of antimicrobial PDT include a broad spectrum of action, efficient
      killing against wild-type as well as drug-resistant pathogens. Therefore,
      antimicrobial PDT could be valuable to rapidly reduce the microbial burden during
      the management of local infections, especially for the antibiotic resistance. A
      variety of photosensitizers have been examined its efficacy against pathogens. To
      increase the efficacy of photosensitizers, various drug delivery systems have
      been developed. Among these carrier systems, liposomes showed their PDT efficacy
      and safety in delivering photosensitizers. This review is focused on the
      application of liposomes mediated photodynamic inactivation of bacteria along
      with the discussion of few of recent patents. 

PMID- 23550542
TI  - Pleistocene climate change and the origin of two desert plant species, Pugionium
      cornutum and Pugionium dolabratum (Brassicaceae), in northwest China.
AB  - Pleistocene climate change has had an important effect in shaping intraspecific
      genetic variation in many species; however, its role in driving speciation is
      less clear. We examined the possibility of a Pleistocene origin of the only two
      representatives of the genus Pugionium (Brassicaceae), Pugionium cornutum and
      Pugionium dolabratum, which occupy different desert habitats in northwest China.
      We surveyed sequence variation for internal transcribed spacer (ITS), three
      chloroplast (cp) DNA fragments, and eight low-copy nuclear genes among
      individuals sampled from 11 populations of each species across their geographic
      ranges. One ITS mutation distinguished the two species, whereas mutations in
      cpDNA and the eight low-copy nuclear gene sequences were not species-specific.
      Although interspecific divergence varied greatly among nuclear gene sequences, in
      each case divergence was estimated to have occurred within the Pleistocene when
      deserts expanded in northwest China. Our findings point to the importance of
      Pleistocene climate change, in this case an increase in aridity, as a cause of
      speciation in Pugionium as a result of divergence in different habitats that
      formed in association with the expansion of deserts in China.

PMID- 23550546
TI  - Special features of gram-positive bacterial eradication by photosensitizers.
AB  - Antibiotic resistance of pathogenic bacteria is a major concern and presents a
      special challenge for development of alternative antibacterial modalities. One of
      these alternative approaches is based on using the photodynamic therapy (PDT) for
      eradicating bacteria. Photosensitizer-induced PDT exhibits unique properties and
      demonstrates efficient microbe-killing effects. The efficient and irreversible
      antimicrobial effects of PDT are not dependent on the antibiotic susceptibility
      of the pathogenic bacteria to antibiotics. Gram-positive bacteria exhibit
      efficient binding of the photosensitizer to the bacterial barriers, leading to
      immediate photoinactivation of the bacteria. Photoinactivation of Gram-positive
      bacteria by various photosensitizers has become a high priority, since these
      bacteria are responsible for life-threatening infections in humans, especially in
      the elderly and in compromised hosts in whom they cause hospital-acquired
      infections. The present review concentrates on the photoinactivation of
      Staphylococi, Streptococci, Propionibacterium acnes, Deinococcus radiodurans,
      aerobic spore-forming Bacilli by various photosensitizers and by various methods
      described in numerous works and patents. 

PMID- 23550545
TI  - Antimicrobial photodynamic therapy to kill Gram-negative bacteria.
AB  - Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a
      new promising strategy to eradicate pathogenic microorganisms such as Gram
      positive and Gram-negative bacteria, yeasts and fungi. The search for new
      approaches that can kill bacteria but do not induce the appearance of undesired
      drug-resistant strains suggests that PDT may have advantages over traditional
      antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the
      simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS).
      Several PS have been studied for their ability to bind to bacteria and
      efficiently generate reactive oxygen species (ROS) upon photo-stimulation. ROS
      are formed through type I or II mechanisms and may inactivate several classes of
      microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa,
      which are typically characterized by an impermeable outer cell membrane that
      contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the
      sensitive inner membrane and cell wall. This review covers significant peer
      reviewed articles together with US and World patents that were filed within the
      past few years and that relate to the eradication of Gram-negative bacteria via
      PDI or PDT. It is organized mainly according to the nature of the PS involved and
      includes natural or synthetic food dyes; cationic dyes such as methylene blue and
      toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins,
      porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized
      fullerenes; nanoparticles combined with different PS; other formulations designed
      to target PS to bacteria; photoactive materials and surfaces; conjugates between
      PS and polycationic polymers or antibodies; and permeabilizing agents such as
      EDTA, PMNP and CaCl2. The present review also covers the different laboratory
      animal models normally used to treat Gram-negative bacterial infections with
      antimicrobial PDT.

PMID- 23550547
TI  - Dedicated education unit: implementing an innovation in replication sites.
AB  - An important measure of an innovation is the ease of replication and achievement
      of the same positive outcomes. The dedicated education unit (DEU) clinical
      education model uses a collaborative academic-service partnership to develop an
      optimal learning environment for students. The University of Portland adapted
      this model from Flinders University, Australia, to increase the teaching capacity
      and quality of nursing education. This article identifies DEU implementation
      essentials and reports on the outcomes of two replication sites that received
      consultation support from the University of Portland. Program operation
      information, including education requirements for clinician instructors, types of
      patient care units, and clinical faculty-to-student ratios is presented. Case
      studies of the three programs suggest the DEU model is adaptable to a range of
      different clinical settings and continues to show promise as one strategy for
      addressing the nurse faculty shortage and strengthening academic-clinical
      collaborations while maintaining quality clinical education for students.

PMID- 23550548
TI  - Pilot test of a three-station palliative care observed structured clinical
      examination for multidisciplinary trainees.
AB  - Developing effective communication and symptom assessment skills is an important
      component of palliative care training for advance practice nurses (APNs) and
      other health care providers. The purpose of this project was to develop and pilot
      test a three-station palliative care Observed Structured Clinical Examination
      (OSCE) for APN students and physician fellows. Three stations included discussing
      goals of care, breaking bad news, and assessing delirium. Measures included the
      Interpersonal Skills Tool, Station Checklists, the OSCE Evaluation Tool, and a
      focus group to solicit learners' perspectives about the experience. Findings
      showed that learners evaluated the exercise as appropriate for their level of
      training and that standardized patients were convincing and provided helpful
      feedback. Learner self-evaluation means were significantly lower than those of
      standardized patient or faculty, and faculty raters demonstrated low interrater
      reliability. Initial evaluation suggests a three-station palliative care OSCE
      exercise is effective for multidisciplinary learners, although additional
      refinement is necessary.

PMID- 23550549
TI  - Radiant thinking and the use of the mind map in nurse practitioner education.
AB  - The concept of radiant thinking, which led to the concept of mind mapping,
      promotes all aspects of the brain working in synergy, with thought beginning from
      a central point. The mind map, which is a graphical technique to improve creative
      thinking and knowledge attainment, utilizes colors, images, codes, and dimensions
      to amplify and enhance key ideas. This technique augments the visualization of
      relationships and links between concepts, which aids in information acquisition,
      data retention, and overall comprehension. Faculty can promote students' use of
      the technique for brainstorming, organizing ideas, taking notes, learning
      collaboratively, presenting, and studying. These applications can be used in
      problem-based learning, developing plans of care, health promotion activities,
      synthesizing disease processes, and forming differential diagnoses. Mind mapping
      is a creative way for students to engage in a unique method of learning that can
      expand memory recall and help create a new environment for processing
      information.

PMID- 23550550
TI  - Myocardial performance index and aortic distensibility in patients with different
      left ventricle geometry in newly diagnosed essential hypertension.
AB  - BACKGROUND: Abnormal left ventricular (LV) geometric patterns, particularly
      concentric LV hypertrophy, are associated with a greater risk of hypertensive
      complications. The aim of this study was to investigate the association between
      LV myocardial performance index (LVMPI) and aortic distensibility (AD) with
      different LV geometric patterns in patients with newly diagnosed hypertension
      (HT). METHODS: We studied 181 patients with newly diagnosed HT (mean age 51.7 +/-
      5.4 years) and 39 healthy control subjects (mean age 51.2 +/- 5.1 years).
      Echocardiographic examination was performed in all subjects. Four different
      geometric patterns were determined in hypertensive patients according to LV mass
      index (LVMI) and relative wall thickness (RWT). AD was calculated from the
      echocardiographically derived ascending aorta diameters and haemodynamic pressure
      measurements. LVMPI was calculated from the tissue Doppler-derived ejection time,
      isovolumic contraction and relaxation times. RESULTS: The highest LVMPI and the
      lowest AD values were observed in concentric hypertrophy group compared with
      control, normal geometry, concentric remodelling and eccentric hypertrophy groups
      (p < 0.05, for all). LVMPI was associated with LVMI (r = 0.497, p < 0.001), RWT
      (r = 0.270, p < 0.001), AD (r = -0.316, p < 0.001) and E deceleration time (r =
      0.171, p = 0.02) in bivariate analysis. In multiple linear regression analysis,
      LVMPI was independently related to LVMI (beta = 0.381, p < 0.001) and AD (beta = 
      0.263, p = 0.001). CONCLUSIONS: The LVMPI was highest and AD was lowest in
      patients with concentric hypertrophy. The LVMPI was independently associated with
      LVMI and AD in hypertensive patients.

PMID- 23550551
TI  - A systematic study of the features critical for designing a high avidity
      multivalent aptamer.
AB  - Macromolecular interactions are central to the regulation and execution of many
      key biological processes, and therefore, they are attractive targets for drug
      discovery. Previously, we identified an RNA aptamer for the heat shock factor
      (HSF1), which is capable of interfering with the binding of HSF1 to its cognate
      DNA elements. Here we report the significant enhancement of avidity through
      dimerization of this aptamer. In particular, we describe the effect of 2 factors
      in designing a multivalent aptamer: the distance between active subunits and the
      flexibility of the linkage.

PMID- 23550552
TI  - Association of hepatic lipase gene polymorphisms with hypertriglyceridemia and
      low high-density lipoprotein-cholesterol levels among South Indian subjects
      without diabetes.
AB  - AIM: The aim of this study was to investigate the association of four variants of
      the hepatic lipase (HL [or LIPC]) gene with various lipid parameters among South
      Indian subjects with normal glucose tolerance (NGT). SUBJECTS AND METHODS: In
      total, 747 NGT subjects were randomly selected from the Chennai Urban Rural
      Epidemiological Study (CURES). Serum triglycerides, serum cholesterol, and high
      density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912
      autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Genotyping of HL gene
      variants was done by the polymerase chain reaction-restriction fragment length
      polymorphism method, and 20% of samples were sequenced to validate the genotypes
      obtained. Haplotype analysis was also carried out. RESULTS: The TT genotype of
      the rs1800588 C/T (C-480T) polymorphism was significantly associated with
      hypertriglyceridemia, with an adjusted odds ratio of 2.58 (95% confidence
      interval 1.38-4.85, P=0.003), whereas those with the CC genotype of the rs6074
      A/C (Thr479Thr) had significantly lower HDL-C levels (41.3+/-9.8 mg/dL) compared
      with the AA genotype (43.6+/-10.2 mg/dL, P=0.02). Haplotype analysis showed the
      TGC haplotype was significantly associated with low HDL-C levels. CONCLUSIONS:
      Among South Indian subjects without diabetes, the rs1800588 C/T (C-480T) and
      rs6074 C/A (Thr479Thr) variants of the HL gene are associated with
      hypertriglyceridemia and low HDL-C, respectively. The TGC haplotype was
      significantly associated with low HDL-C.

PMID- 23550553
TI  - Evaluation of the mean absolute glucose change as a measure of glycemic
      variability using continuous glucose monitoring data.
AB  - BACKGROUND: The mean absolute glucose (MAG) change, originally developed to
      assess associations between glycemic variability (GV) and intensive care unit
      mortality, has not yet been validated. We used continuous glucose monitoring
      (CGM) datasets from patients with diabetes to assess the validity of MAG and to
      quantify associations with established measures of GV. SUBJECTS AND METHODS:
      Validation was based on retrospective analysis of 72-h CGM data collected during
      clinical studies involving 815 outpatients (48 with type 1 diabetes and 767 with
      type 2 diabetes). Measures of GV included SD around the sensor glucose,
      interquartile range, mean amplitude of glycemic excursions, and the continuous
      overlapping net glycemic action indices at 1, 3, and 6 h. MAG was calculated
      using 5-min, 60-min, and seven-point glucose profile sampling intervals;
      correlations among the variability measures and effects of sampling frequency
      were assessed. RESULTS: Strong linear correlations between MAG change and
      classical markers of GV were documented (r=0.587-0.809, P<0.001 for all), whereas
      correlations with both glycosylated hemoglobin and mean sensor glucose were found
      to be weak (r=0.246 and r=0.378, respectively). The magnitude of MAG change
      decreased in a nonlinear fashion (P<0.001), as intervals between glucose
      measurements increased. MAG change, as calculated from 5-min sensor glucose
      readings, did reflect relatively small differences in glucose fluctuations
      associated with glycemic treatment modality. CONCLUSIONS: MAG change represents a
      valid GV index if closely spaced sensor glucose measurements are used, but does
      not provide any advantage over variability indices already used for assessing
      diabetes control.

PMID- 23550554
TI  - Text message interventions for children and adolescents with type 1 diabetes: a
      systematic review.
AB  - Daily management challenges and declines in glycemic control are evident among
      youth with type 1 diabetes (T1D) as responsibility for care transitions from
      parent to youth. Many behavioral interventions developed for youth and their
      caregivers have demonstrated a small yet significant impact, and one method to
      potentially augment or increase their potency may be the use of mobile health
      strategies such as text messages. The primary aim of this systematic review was
      to evaluate the current literature regarding interventions incorporating text
      message-based interventions for youth with T1D. Feasibility was demonstrated
      across all text message programs, but participant satisfaction and glycated
      hemoglobin results were mixed. Retention rates varied, and technical difficulties
      were reported in several studies. Current evidence suggests that text message
      based interventions that include text messages are feasible and enjoyable, but
      yet their clinical significance for long-term daily T1D management behaviors and
      glycemic control is unclear. Researchers are recommended to carefully consider
      the format, frequency, and timing of text message interventions and to fully test
      software before implementation. Future research needs include utilization of
      experimental designs such as randomized controlled trials, SMART design trials,
      and stepped wedge design trials to clarify specific medical and psychosocial
      outcomes, the role of caregivers/peers and incentives, and utility in clinical
      settings.

PMID- 23550555
TI  - 1-hour venous plasma glucose and incident prediabetes and diabetes in Asian
      indians.
AB  - BACKGROUND: This study evaluated 1-h plasma glucose (1HrPG) levels during an oral
      glucose tolerance test (OGTT) in predicting progression to diabetes and
      prediabetes among individuals with normal glucose tolerance (NGT). SUBJECTS AND
      METHODS: After analyzing the electronic records of 32,809 subjects who had
      undergone an OGTT, we identified 1,179 subjects who had NGT at baseline, defined
      as fasting plasma glucose (FPG) of < 100 mg/dL and 2-h plasma glucose (2HrPG) of
      < 140 mg/dL, who had at least one follow-up OGTT. Receiver operating
      characteristic curves were constructed to derive the optimal 1HrPG values, which
      were associated with the development of diabetes (FPG of >= 126 mg/dL or 2HrPG of
      >= 200 mg/dL) or prediabetes (FPG >= 100 to <1 26 mg/dL or 2HrPG of >= 140 to <
      200 mg/dL) at follow-up in these NGT subjects. RESULTS: On follow-up, 148 (12.6%)
      subjects developed diabetes, and 392 (33.2%) developed prediabetes. In those with
      1HrPG values >= 155 mg/dL, 19.5% converted to diabetes compared with 10% among
      those with 1HrPG of >=143 to < 155 mg/dL and 6.6% in those with 1HrPG < 143
      mg/dL. Comparative figures for conversion to prediabetes were 52.2% (1HrPG values
      >= 155 mg/dL), 39.3% (1HrPG >= 143 to <155 mg/dL), and 26.0% (1HrPG < 143 mg/dL).
      The time to development of diabetes (mean +/- SE) was also significantly shorter
      among those with 1HrPG values of >= 155 mg/dL (9.0+/-0.3 years) compared with
      those with 1HrPG >= 143 to < 155 mg/dL (10.6 +/- 0.5 years) and 1HrPG < 143 mg/dL
      (11.6 +/- 0.2 years). CONCLUSIONS: Among NGT subjects with elevated 1HrPG values
      during an OGTT, progression to diabetes and prediabetes is greater, and the rate
      of progression is also faster.

PMID- 23550556
TI  - Disordered eating behaviors in youth with type 1 diabetes: prospective pilot
      assessment following initiation of insulin pump therapy.
AB  - BACKGROUND: There is risk for disordered eating behaviors in type 1 diabetes,
      especially related to insulin manipulation. Implementation of insulin pump
      therapy may encourage either normalization of eating behaviors or a greater focus
      on food intake due to renewed emphasis on carbohydrate counting. There is need
      for prospective studies to assess disordered eating behaviors upon implementation
      of pump therapy using diabetes-specific measurement tools. SUBJECTS AND METHODS:
      In a multicenter pilot study, 43 youth with type 1 diabetes, 10-17 years old,
      were assessed prior to pump initiation and after 1 and 6 months of pump therapy.
      Youth completed the Diabetes-specific Eating Problems Survey-Revised (DEPS-R), a
      validated measure of risk for both diabetes-specific and general disordered
      eating behaviors. RESULTS: Youth (45% female), 13.3 years old with diabetes for
      2.1 years, had a mean hemoglobin A1c of 8.3+/-1.3% (68+/-14.5 mmol/mol) at
      baseline. DEPS-R scores decreased over time (P=0.01). Overall rate of high risk
      for eating disorders was low. Overweight/obese youth endorsed more disordered
      eating behaviors than normal-weight participants. DEPS-R scores were correlated
      with z-score for body mass index at all three time points and with hemoglobin A1c
      after 1 and 6 months. Hemoglobin A1c did not change significantly over the 6
      months and was higher in overweight/obese compared with normal-weight
      participants. CONCLUSIONS: Initiation of insulin pump therapy was associated with
      diminished endorsement of disordered eating behaviors in youth with type 1
      diabetes. Longer follow-up studies are needed to assess the impact of insulin
      pump therapy on glycemic control, weight status, and disordered eating behaviors
      in this vulnerable population.

PMID- 23550558
TI  - The interaction between axes of inequality in studies on discrimination, stigma
      and HIV/AIDS: contributions to the recent international literature.
AB  - This study aimed to conduct a systematic literature review in order to identify
      how recent studies have addressed the interaction between social inequality and
      the processes of exclusion and marginalisation related to HIV/AIDS stigma and
      discrimination. The review was conducted using PubMed and Scopus databases and
      included publications from 2008 to 2011. Of 497 summaries found in the review, 42
      were selected and classified based on topic, population, axes of inequality
      employed, conceptualisation of stigma and relationship between stigma and
      vulnerability. Results demonstrated that there is a predominance of research on
      stigma and discrimination towards people living with HIV/AIDS, sexual and
      racial/ethnic minorities and migrants. The axes of inequality examined in the
      literature were linked to specific cultural and socio-economic dimensions and
      analysed as factors that behave synergistically to increase social groups'
      vulnerability to HIV. Half of the 42 articles viewed expression of
      stigma/discrimination to be the result of power dynamics that reinforce the
      processes of social exclusion. The other half of the articles tended to describe
      stigma as intrinsic to social interaction. Some researchers are making a visible
      effort to devise consistent theoretical and methodological approaches in order to
      understand stigma as a complex social process produced at the intersection of
      different axes of inequality. These efforts provide vital information that can
      inform how best to address HIV/AIDS stigma.

PMID- 23550559
TI  - An unusual pattern of decomposition associated with suicidal electrocution in a
      bath.
AB  - A 51-year-old man was found dead face down and partially submerged in a bathtub
      alongside two hairdryers. The hairdryers had continued to work, as the victim had
      bypassed the electrical board of the house prior to dropping them into the water.
      This had resulted in death due to electrocution, with subsequent heating of the
      bath water causing marked putrefaction and softening of the immersed body parts.
      The back and feet, which were not submerged, were preserved. The degree of
      anterior decomposition was not in keeping with the postmortem interval; however,
      regional decomposition with sparing of the back and feet provided a clue at
      autopsy as to the sequence of events. Individuals with training in, or knowledge
      of, electrical circuitry are capable of modifying domestic wiring so that safety
      switches and/or fuses can be bypassed ensuring that electrical devices will
      continue to function even while under water. 

PMID- 23550560
TI  - Effects of molecular weight distribution and chemical properties of natural
      organic matter on gold nanoparticle aggregation.
AB  - The complexity of natural organic matter (NOM) motivates determination of how
      specific components in a NOM mixture interact with and affect nanoparticle (NP)
      behavior. The effects of two Suwannee River NOM fractions (separated by a 100,000
      g/mol ultrafiltration membrane) on gold NP aggregation are compared. The weight
      average molecular weight, Mw, for the unfractionated NOM was 23,300 g/mol,
      determined by size exclusion chromatography with multiangle light scattering. The
      NOM was comprised of ~1.8 wt % of >100,000 g/mol retentate (NOMr, Mw = 691,000
      g/mol) and 98 wt % of filtrate (NOMf, Mw = 12,800 g/mol). Ten ppm of NOMr
      provided significantly better NP stability against aggregation than 10 ppm of
      NOMf in 100 mM NaCl due to steric effects. In the unfractionated NOM, the
      relative importance of the two components was concentration-dependent. For a low
      concentration of unfractionated NOM (10 ppm), both fractions contributed to the
      NOM effects; for a high concentration (560 ppm), NP stability was controlled by
      the small amount (10 ppm) of NOMr present, rather than the higher amount (550
      ppm) of NOMf. Therefore, large humic aggregates in a heterogeneous NOM sample can
      have disproportionately strong effects, and characterization of Mw distributions
      (rather than average Mw) may be required to explain NOM effects on NP behavior.

PMID- 23550561
TI  - Preschoolers' recognition of emotional expressions: relationships with other
      neurocognitive capacities.
AB  - We cross-sectionally examined the development of the ability to recognize facial
      expressions of emotions in preschool-aged children and the relationship between
      this ability and other neurocognitive capacities, that is, attention/executive
      functions, language, memory/learning, sensorimotor functions, theory of mind, and
      visuospatial processing. Children aged 3 to 6 years with no significant
      developmental deficits (N = 370) were assessed with a nonverbal matching task of
      emotion recognition ability: The Affect Recognition subtest from the NEPSY-II.
      The relationship between emotion recognition ability and other neurocognitive
      capacities was analyzed using correlation, regression, and commonality analyses.
      The results showed that (a) emotion recognition ability improved with age-this
      development decelerating mildly between ages 5 and 6-(b) emotion recognition
      ability correlated with all other neurocognitive capacities, and (c) language,
      attention/executive functions, and theory of mind were significant predictors of
      emotion recognition ability in the regression analysis. As revealed by the
      commonality analysis, and in contrast to most previous studies, language was the
      most important predictor of nonverbal emotion recognition ability. These results
      suggest that nonverbal emotion matching is an early maturing skill that develops
      in relation to other neurocognitive capacities, especially linguistic ability. 

PMID- 23550562
TI  - Late-onset skin fragility in childhood: a case of junctional epidermolysis
      bullosa of late onset caused by a missense mutation in COL17A1.

PMID- 23550563
TI  - Short-term effects of continuous positive airway pressure on sex hormones in men
      and women with sleep apnoea syndrome.
AB  - Patients with sleep apnoea syndrome (SAS) suffer from symptoms of hypogonadism.
      Besides surgical interventions, in some cases, the standard care of SAS for most
      patients is continuous positive airway pressure (CPAP). Studies focusing on the
      long-term effects of CPAP on testosterone levels revealed conflicting results.
      None of the studies included female patients with SAS. The aim of our study was
      to analyse and compare sex hormone levels in saliva before and after a night
      without and with CPAP in women and men with SAS. The results were negative. One
      night with CPAP did not affect the dynamics of sex hormones, neither in men nor
      in women. Future studies should focus on long-term effects of CPAP in both
      genders. 

PMID- 23550564
TI  - Cancer incidence in persons with elevated cobalamin levels.
AB  - BACKGROUND: Elevated cobalamin level (ECL) is an epiphenomenon for several cancer
      types. The clinical significance of ECL at routine testing is, however, unknown.
      The aim of this study was to examine cancer incidences among persons with ECL.
      DESIGN: In a cohort study, Funen County residents (inhabitants 476,580), Denmark,
      without cancer or injected cobalamin prescriptions were followed from first
      cobalamin measurement during 1999-2009. Follow-up was stratified according to
      age, gender, and whether the cobalamin level was elevated (> 1,200 pmol/L). Data
      from national registers on age-specific incidence of cancer in the general
      population were used to calculate standardised morbidity ratio (SMR). RESULTS: A
      total of 490 persons with ECL and 40,104 with non-ECL were followed. Median age
      was 61 [IQR 44-77] years. Average follow-up was 2.0 years for ECL subjects and
      2.7 years for non-ECL subjects. Cancer was diagnosed within the first 6 months of
      follow-up in 6.7% (CI 4.7-9.3) of ECL subjects and 2.6% (CI 2.4-2.7) of non-ECL
      subjects. In ECL and non-ECL subjects, SMR for cancer diagnoses were 15.1 (CI
      10.4-21.2) and 5.0 (CI 4.7-5.3) within the first 6 months and 3.7 (CI 1.4-8.1)
      and 1.8 (CI 1.6-2.0) in the following six-month interval. Review of medical
      records revealed a suspicion of cancer or performance of relevant diagnostic
      tests in 87% at the time of cobalamin measurement. CONCLUSIONS: Persons with ECL
      have a high incidence of cancer partly explained by the reasons for measuring
      cobalamin. It remains to be determined whether accidentally found ECL would
      justify a search for cancers.

PMID- 23550565
TI  - New methodologies for the extraction and fractionation of bioactive carbohydrates
      from mulberry (Morus alba) leaves.
AB  - Pressurized liquid extraction (PLE) was applied for the first time to extract
      bioactive low molecular weight carbohydrates (iminosugars and inositols) from
      mulberry ( Morus alba ) leaves. Under optimized conditions, PLE provided a
      similar yield to the conventional process used to extract these bioactives, but
      in less time (5 vs 90 min). To remove carbohydrates that interfere with the
      bioactivity of iminosugars from PLE extracts, two fractionation treatments were
      evaluated: yeast ( Saccharomyces cerevisiae ) incubation and cation-exchange
      chromatography (CEC). Both methods allowed complete removal of major soluble
      carbohydrates (fructose, glucose, galactose, and sucrose), without affecting the
      content of mulberry bioactives. As an advantage over CEC, the yeast treatment
      preserves bioactive inositols, and it is an affordable methodology that employs
      food grade solvents. This work found PLE followed by yeast treatment to be an
      easily scalable and automatable procedure that can be implemented in the food
      industry.

PMID- 23550566
TI  - C4 plants use fluctuating light less efficiently than do C3 plants: a study of
      growth, photosynthesis and carbon isotope discrimination.
AB  - Plants in the field are commonly exposed to fluctuating light intensity, caused
      by variable cloud cover, self-shading of leaves in the canopy and/or leaf
      movement due to turbulence. In contrast to C3 plant species, only little is known
      about the effects of dynamic light (DL) on photosynthesis and growth in C4
      plants. Two C4 and two C3 monocot and eudicot species were grown under steady
      light or DL conditions with equal sum of daily incident photon flux. We measured
      leaf gas exchange, plant growth and dry matter carbon isotope discrimination to
      infer CO2 bundle sheath leakiness in C4 plants. The growth of all species was
      reduced by DL, despite only small changes in steady-state gas exchange
      characteristics, and this effect was more pronounced in C4 than C3 species due to
      lower assimilation at light transitions. This was partially attributed to
      increased bundle sheath leakiness in C4 plants under the simulated lightfleck
      conditions. We hypothesize that DL leads to imbalances in the coordination of C4
      and C3 cycles and increasing leakiness, thereby decreasing the quantum efficiency
      of photosynthesis. In addition to their other constraints, the inability of C4
      plants to efficiently utilize fluctuating light likely contributes to their
      absence in such environments as forest understoreys. 

PMID- 23550567
TI  - A long curved needle with a large radius for uterine compression suture.

PMID- 23550568
TI  - Editorial.

PMID- 23550570
TI  - Opicinus de Canistris: concluding lecture by C.G. Jung, Eranos, Ascona, 1943:
      notes taken [probably] by Rivkah Scharf Kluger.

PMID- 23550571
TI  - Further studies on Jung's Eranos seminar on Opicinus de Canistris.

PMID- 23550572
TI  - Reflections on knowledge and experience.
AB  - As analysts become more experienced, theoretical knowledge becomes more
      integrated and implicit and is gradually transformed into the practical wisdom
      (phronesis) described by Aristotle. While this leads to greater freedom in ways
      of working, it remains conditional on the consistent disciplined practice
      represented by the analytic attitude. In the context of my own development as an
      analyst, I suggest that increasingly the analyst works from the self rather than
      the ego and link this with Fordham's account of 'not knowing beforehand'. Some
      implications for boundaries, enactment and the use of personal disclosure are
      discussed in relation to clinical material. I compare analysis with the wisdom
      traditions of religious practice and suggest that analysis is concerned with a
      way of living rooted in humane values of compassion and benevolence.

PMID- 23550573
TI  - A structural-phenomenological typology of mind-matter correlations.
AB  - We present a typology of mind-matter correlations embedded in a dual-aspect
      monist framework as proposed by Pauli and Jung. They conjectured a picture in
      which the mental and the material arise as two complementary aspects of one
      underlying psychophysically neutral reality to which they cannot be reduced and
      to which direct empirical access is impossible. This picture suggests structural,
      persistent, reproducible mind-matter correlations by splitting the underlying
      reality into aspects. In addition, it suggests induced, occasional, evasive mind
      matter correlations above and below, respectively, those stable baseline
      correlations. Two significant roles for the concept of meaning in this framework
      are elucidated. Finally, it is shown that the obtained typology is in perfect
      agreement with an empirically based classification of the phenomenology of mind
      matter correlations as observed in exceptional human experiences.

PMID- 23550574
TI  - A commentary on 'A structural-phenomenological typology of mind-matter
      correlations' by H. Atmanspacher and W. Fach.

PMID- 23550576
TI  - Analytical psychology and the ghost of Lamarck: did Jung believe in the
      inheritance of acquired characteristics?
AB  - Whether Jung was a Lamarckian or not has always been a hotly debated topic, both
      within the post-Jungian community and amongst scholars with an interest in Jung
      in the wider academic community. Yet surprisingly few substantial pieces of work
      have been dedicated to it and, to my mind, no one has yet managed to do justice
      to all the subtleties involved. The scholars who have claimed that Jung is a
      Lamarckian have, for the most part, oversimplified the debate by failing to
      discuss the passages in which Jung appears to be defending himself against
      Lamarckism; the scholars who have defended Jung against Lamarckism, however, have
      as a rule not adequately dealt with the question of whether these passages
      actually get Jung off the hook. This paper will attempt to correct this imbalance
      by putting forward four key passages spanning Jung's career that all represent
      conclusive evidence that Jung was indeed a Lamarckian. After discussing these, it
      will then deal in detail with the passages in which Jung appears to be defending
      himself against Lamarckism, making the case that they do not represent a defence
      against Lamarckism at all and have therefore generally been misinterpreted by
      many scholars.

PMID- 23550577
TI  - Are archetypes transmitted or emergent? A response to Christian Roesler.
AB  - In this paper the author argues that Jung's concept of archetype should not be
      reduced to an univocal definition. Jung himself proposed many definitions of this
      concept, some of them being partially or totally contradictory to others. A
      univocal and logical way of thinking can lead us to refute and reject part of
      those definitions, but a complex way of thinking, as proposed by Edgar Morin or
      Roy Bhaskar for example, can allow us to consider that those apparent
      contradictions in Jung's definitions of archetype reflect the complexity of the
      psychic reality. The main argument of the author is that Jung was missing the
      epistemological concept of emergence (which appeared in science at the time of
      his death) and that he tried to express it with the epistemological concepts of
      his time.

PMID- 23550583
TI  - Nine-spined stickleback (Pungitius pungitius): an emerging model for evolutionary
      biology research.
AB  - The nine-spined stickleback (Pungitius pungitius) is emerging as a model for
      evolutionary biology, genetic, and behavioral research in the wake of its better
      known relative, the three-spined stickleback (Gasterosteus aculeatus). This
      interest has been fed by its fascinating biological features, such as the
      repeated evolution of similar phenotypes in isolated pond populations. A large
      body of recent research has uncovered the finding that pond nine-spined
      sticklebacks have evolved numerous morphological, life history, neuroanatomical,
      and behavioral adaptations-possibly in response to reduced threat of fish
      predation-which differentiate them from their marine conspecifics. These
      features, together with insights from recent population genetic studies, suggest
      that this species provides an interesting model for studies aiming to understand
      and differentiate between-genetic convergence and parallelism as underlying
      mechanism(s) of evolution of similar phenotypes in multiple independent sites.
      This review provides a synopsis of and reflections on the insights borne out of
      recent studies of nine-spined sticklebacks-the little sister of ecology's "new
      supermodel."

PMID- 23550584
TI  - Effects of noise and working memory capacity on memory processing of speech for
      hearing-aid users.
AB  - OBJECTIVES: It has been shown that noise reduction algorithms can reduce the
      negative effects of noise on memory processing in persons with normal hearing.
      The objective of the present study was to investigate whether a similar effect
      can be obtained for persons with hearing impairment and whether such an effect is
      dependent on individual differences in working memory capacity. DESIGN: A
      sentence-final word identification and recall (SWIR) test was conducted in two
      noise backgrounds with and without noise reduction as well as in quiet. Working
      memory capacity was measured using a reading span (RS) test. STUDY SAMPLE: Twenty
      six experienced hearing-aid users with moderate to moderately severe
      sensorineural hearing loss. RESULTS: Noise impaired recall performance. Competing
      speech disrupted memory performance more than speech-shaped noise. For late list
      items the disruptive effect of the competing speech background was virtually
      cancelled out by noise reduction for persons with high working memory capacity.
      CONCLUSIONS: Noise reduction can reduce the adverse effect of noise on memory for
      speech for persons with good working memory capacity. We argue that the mechanism
      behind this is faster word identification that enhances encoding into working
      memory.

PMID- 23550585
TI  - Sex-specific impairment of spatial memory in rats following a reminder of
      predator stress.
AB  - It has been suggested that cognitive impairments exhibited by people with post
      traumatic stress disorder (PTSD) result from intrusive, flashback memories
      transiently interfering with ongoing cognitive processing. Researchers have
      further speculated that females are more susceptible to developing PTSD because
      they form stronger traumatic memories than males, hence females may be more
      sensitive to the negative effects of intrusive memories on cognition. We have
      examined how the reminder of a naturalistic stress experience would affect rat
      spatial memory and if sex was a contributing factor to such effects. Male and
      female Sprague-Dawley rats were exposed, without contact, to an adult female cat
      for 30 min. Five weeks later, the rats were trained to locate a hidden platform
      in the radial-arm water maze and given a single long-term memory test trial 24 h
      later. Before long-term memory testing, the rats were given a 30-min reminder of
      the cat exposure experienced 5 weeks earlier. The results indicated that the
      stress reminder impaired spatial memory in the female rats only. Control
      manipulations revealed that this effect was not attributable to the original cat
      exposure adversely impacting learning that occurred 5 weeks later, or to merely
      exposing rats to a novel environment or predator-related cues immediately before
      testing. These findings provide evidence that the reminder of a naturalistic
      stressful experience can impair cognitive processing in rats; moreover, since
      female rats were more susceptible to the memory-impairing effects of the stress
      reminder, the findings could lend insight into the existing sex differences in
      susceptibility to PTSD.

PMID- 23550586
TI  - Genome size variation in wild and cultivated maize along altitudinal gradients.
AB  - It is still an open question as to whether genome size (GS) variation is shaped
      by natural selection. One approach to address this question is a population-level
      survey that assesses both the variation in GS and the relationship of GS to
      ecological variants. We assessed GS in Zea mays, a species that includes the
      cultivated crop, maize, and its closest wild relatives, the teosintes. We
      measured GS in five plants of each of 22 maize landraces and 21 teosinte
      populations from Mexico sampled from parallel altitudinal gradients. GS was
      significantly smaller in landraces than in teosintes, but the largest component
      of GS variation was among landraces and among populations. In maize, GS
      correlated negatively with altitude; more generally, the best GS predictors were
      linked to geography. By contrast, GS variation in teosintes was best explained by
      temperature and precipitation. Overall, our results further document the size
      flexibility of the Zea genome, but also point to a drastic shift in patterns of
      GS variation since domestication. We argue that such patterns may reflect the
      indirect action of selection on GS, through a multiplicity of phenotypes and life
      history traits.

PMID- 23550587
TI  - Lactate study using umbilical cord blood: agreement between Lactate Pro hand-held
      devices with blood gas analyser and evaluation of lactate stability over time.
AB  - BACKGROUND: Lactate measurements have become increasingly preferred over pH
      analysis in the evaluation of fetal acidaemia in labour. In a busy labour ward,
      often the umbilical cord may be sampled late and as a result yield unreliable
      lactate values. AIM: To investigate the agreement of hand-held device Lactate Pro
      with a reference method blood gas analyser and evaluate the stability of
      umbilical cord lactate values over time. METHODS: Prospective study carried out
      at elective caesarean section. Sixteen umbilical cords were double clamped
      immediately after delivery with paired arterial and venous blood samples
      collected by an independent researcher, at varying time intervals, and processed
      by two Lactate Pro devices and a reference method blood gas analyser. RESULTS: A
      significant difference of -0.41 to 0.10 mmol/L was found when different groups of
      Lactate Pro devices were compared with blood gas analyser at lactate values up to
      5.70 mmol/L, with average lactate value of 2.45 mmol/L. Over time, there is
      progressive rise in lactate samples obtained from the umbilical cord. CONCLUSION:
      Lactate Pro devices have a significant difference, but when used in clinical
      practice on cord blood after delivery, this is unlikely to be meaningful. In
      intrapartum fetal surveillance, a systematic overestimation might lead to
      unnecessary intervention. It is possible to retrospectively predict the likely
      level of lactate at birth in delayed cord samples.

PMID- 23550588
TI  - Transgenesis of the Wolffian duct visualizes dynamic behavior of cells undergoing
      tubulogenesis in vivo.
AB  - Deciphering how the tubulogenesis is regulated is an essential but unsolved issue
      in developmental biology. Here, using Wolffian duct (WD) formation in chicken
      embryos, we have developed a novel method that enables gene manipulation during
      tubulogenesis in vivo. Exploiting that WD arises from a defined site located
      anteriorly in the embryo (pronephric region), we targeted this region with the
      enhanced green fluorescent protein (EGFP) gene by the in ovo electroporation
      technique. EGFP-positive signals were detected in a wide area of elongating WD,
      where transgenic cells formed an epithelial component in a mosaic manner. Time
      lapse live imaging analyses further revealed dynamic behavior of cells during WD
      elongation: some cells possessed numerous filopodia, and others exhibited
      cellular tails that repeated elongation and retraction. The retraction of the
      tail was precisely regulated by Rho activity via actin dynamics. When
      electroporated with the C3 gene, encoding Rho inhibitor, WD cells failed to
      contract their tails, resulting in an aberrantly elongated process. We further
      combined with the Tol2 transposon-mediated gene transfer technique, and could
      trace EGFP-positive cells at later stages in the ureteric bud sprouting from WD.
      This is the first demonstration that exogenous gene(s) can directly be introduced
      into elongating tubular structures in living amniote embryos. This method has
      opened a way to investigate how a complex tubulogenesis proceeds in higher
      vertebrates.

PMID- 23550589
TI  - A chemoenzymatic total synthesis of the protoilludane aryl ester (+)
      armillarivin.
AB  - The title natural product, 1, has been synthesized in 20 steps from the
      enantiomerically pure cis-1,2-dihydrocatechol 2, itself obtained through the
      whole-cell biotransformation of toluene. The pivotal steps in the reaction
      sequence involve a Diels-Alder cycloaddition reaction between diene 2 and
      cyclopentenone (3) and the photochemically promoted 1,3-acyl rearrangement of the
      bicyclo[2.2.2]oct-4-en-1-one 20 derived from the cycloadduct 4.

PMID- 23550590
TI  - Fracture patterns of glass-ionomer cement overlays versus stainless steel bands
      during endodontic treatment: an ex-vivo study.
AB  - AIM: To compare fracture patterns of posterior teeth temporized with: mesio
      occlusal-distal (MOD) glass-ionomer cement (GIC) interim restorations, stainless
      steel (SS) bands, GIC dome overlays and GIC dome overlays with occlusal temporary
      restorations. METHODOLOGY: The root canals of 92 extracted human premolars and
      molars were prepared with rotary NiTi instruments and dressed with calcium
      hydroxide paste prior to cavity preparation for standardized MOD restorations.
      Teeth were divided into four groups (n = 23) and temporarily restored with: GIC
      interim restorations (GIC group), stainless steel bands (SS group), GIC dome
      overlays (GIC-O group) or GIC dome overlays with intermediate restorative
      material (IRM) in the access cavities (GIC-IRM group). Teeth were subjected to
      compressive axial load until fracture; fracture forces and fracture modes were
      recorded. Statistical analysis included Kaplan-Meier plots, Cox proportional
      hazards model, one-way analysis of variance, chi-square and Fisher's exact tests.
      RESULTS: There was a significantly higher risk of failure in the GIC group
      compared with the SS (P < 0.001), GIC-O (P < 0.001) and GIC-IRM (P = 0.001)
      groups. The mean fracture force for SS was significantly higher than GIC-O (P =
      0.03) and GIC-IRM (P < 0.001). GIC fracture force was significantly lower than
      all other groups (P < 0.001). Significantly fewer unfavourable fractures were
      observed in SS compared with GIC (P = 0.001), GIC-O (P = 0.007) and GIC-IRM (P <
      0.001). CONCLUSIONS: Glass-ionomer cement dome overlays with reduced cuspal
      height and occlusal inclines may be recommended for broken-down posterior teeth,
      without any risk of poor aesthetics, gingival irritation or further proximal
      tooth structure loss. Stainless steel bands may only need to be used in
      extensively broken-down teeth or in the presence of parafunctional habits.

PMID- 23550591
TI  - Quartz crystal microbalance technique for analysis of cooling crystallization.
AB  - A quartz crystal microbalance (QCM) technique is developed for the in situ
      analysis of the cooling crystallization processes of crystal nucleation and
      growth. In contrast to conventional techniques based on property changes in the
      solid or solution phase, the proposed QCM technique simultaneously exploits
      property changes in both the solid and solution phases, such as the solid mass
      and liquid viscosity, to analyze the crystallization processes. When initially
      cooling the solution, an increase in the solution viscosity is reflected in the
      QCM responses for the resonant frequency and resonant resistance. With further
      cooling, the resonant frequency and resonant resistance sharply change at the
      induction point of crystal nucleation, as the viscous liquid film on the sensor
      suddenly shifts to an elastic solid phase. Thereafter, the QCM responses are
      mainly controlled by the suspension viscosity due to simultaneous crystal
      nucleation and growth with further cooling. As a result, the QCM responses allow
      accurate measurement of the induction point and metastable zone width during the
      cooling crystallization. Additional mechanistic information on the
      crystallization, including molecular cluster formation, crystal nucleation, and
      crystal growth, is also extracted from a resonant frequency-resistance plot (F-R
      plot) of the QCM responses when varying the cooling conditions.

PMID- 23550592
TI  - Temporary right ventricular mechanical support in high-risk left ventricular
      assist device recipients versus permanent biventricular or total artificial heart
      support.
AB  - Early planned institution of temporary right ventricular assist device (RVAD)
      support with the CentriMag (Levitronix LLC, Waltham, MA, USA) in left ventricular
      assist device (LVAD) recipients was compared with permanent biventricular assist
      device (BVAD) or total artificial heart (TAH) support. Between 2007 and 2011, 77
      patients (age range: 25-70 years) with preoperative evidence of biventricular
      dysfunction (University of Pennsylvania score >50; University of Michigan score
      >5) were included. Forty-six patients (38 men; median age 54.5 years, range: 25
      70 years) underwent LVAD placement combined with temporary RVAD support (group
      A); in 31 patients (25 men; median age 56.7 years, range: 28-68 years), a
      permanent BVAD or TAH implantation (group B) was performed. Within 30 days, 12
      patients from group A (26.08%) and 14 patients from group B (45.1%) died on
      mechanical support (P = 0.02). Thirty patients (65.2%) in group A were weaned
      from temporary RVAD support and three (6.5%) underwent permanent RVAD (HeartWare,
      Inc., Framingham, MA, USA) placement. A total of 26 patients (56.5%) were
      discharged home in group A versus 17 (54.8%) in group B (P = 0.56). Three
      patients (8.5%) received heart transplantation in group A and six (19.3%) in
      group B (P = 0.04). In group A, 90-day and 6-month survival was 54.3% (n = 25)
      versus 51.6% (n = 16) in group B (P = 0.66). In group A, 1-year survival was
      45.6% (n = 21) versus 45.1% (n = 14) in group B (P = 0.81). The strategy of
      planned temporary RVAD support in LVAD recipients showed encouraging results if
      compared with those of a similar permanent BVAD/TAH population. Weaning from and
      removal of the temporary RVAD support may allow patients to be on LVAD support
      only despite preoperative biventricular dysfunction.

PMID- 23550593
TI  - Acetylcholinesterase and butyrylcholinesterase activities in obese Beagle dogs
      before and after weight loss.
AB  - BACKGROUND: Obesity is the most common nutritional disorder in today's dog
      population and the major risk factor for a number of related diseases. However,
      the exact pathogenesis of obesity-related complications is not always clear. In
      people, butyrylcholinesterase (BChE) is suspected to be involved in lipoprotein
      metabolism and has also been associated with the pathogenesis of inflammatory
      disease, one of the potential complications related to obesity. OBJECTIVES: The
      aim of the study was to evaluate the effect of experimentally induced weight loss
      on BChE and acetylcholinesterase (AChE) in obese dogs to elucidate the possible
      relationship between these 2 enzymes and obesity. METHODS: Six obese intact
      female Beagle dogs were allocated to a weight loss program for 3 months. BChE was
      measured in serum samples using butyrylcholine as substrate, whereas AChE was
      measured in whole blood after inhibition of BChE with ethopropazine and using
      acetylcholine as a substrate. RESULTS: After rapid weight loss serum BChE
      activities were statistically significantly lower (P < .05), whereas AChE
      activities were higher (P < .01). There was a positive correlation between serum
      BChE activity and concentrations of total cholesterol (TCHOL, P < .001), low
      density lipoprotein-cholesterol (LDL-C, P < .001), and triglycerides (P < .05). A
      negative correlation was detected between serum BChE and AChE activities (P <
      .0001), and between AChE activity and serum levels of TCHOL (P < .01), LDL-C (P <
      .01) and high-density lipoprotein-cholesterol (P < .05). CONCLUSIONS: Short-term
      weight loss in obese intact female Beagle dogs resulted in opposite effects in 2
      cholinesterase isoenzyme activities, namely lower BChE and higher AChE
      activities.

PMID- 23550595
TI  - Separation and detection of smokeless powder additives by ultra performance
      liquid chromatography with tandem mass spectrometry (UPLC/MS/MS).
AB  - A reversed phase gradient ultra performance liquid chromatography tandem mass
      spectrometry (UPLC/MS/MS) method has been developed for the analysis of smokeless
      powders. A total of 20 different components were separated by UPLC and detected
      by MS/MS in multiple reaction monitoring (MRM) mode. These compounds included
      diphenylamines, centralites, nitrotoluenes, nitroglycerin, and various
      phthalates. Simultaneous positive and negative electrospray ionization (ESI) was
      used along with negative atmospheric pressure chemical ionization (APCI) to
      detect all compounds in a single analysis. Analysis times were under 8 min with a
      gradient of 10-73% organic at a flow rate of 0.500 mL/min. With this method,
      ultraviolet and MRM limits of detection ranging from 0.08 to 2.6 ng and 0.4-64 ng
      injected were achieved. Commercially available smokeless powders were also
      extracted with methylene chloride and characterized using the developed
      UPLC/MS/MS method. The procedure permits the determination of compositional
      differences between different brands as well as lot-to-lot variations.

PMID- 23550594
TI  - The corpus-predominant gastritis index may serve as an early marker of
      Helicobacter pylori-infected patients at risk of gastric cancer.
AB  - BACKGROUND: To eradicate Helicobacter pylori before the occurrence of
      precancerous changes is important to prevent gastric carcinogenesis. AIM: To
      validate whether the corpus-predominant gastritis index (CGI) can serve as an
      early marker to identify the H. pylori-infected patients at risk of gastric
      carcinogenesis. METHODS: This study enrolled 188 subjects, including 43
      noncardiac gastric cancer patients, 63 of their first-degree relatives and 82 sex
      and age-matched duodenal ulcer patients as controls. All received endoscopy to
      provide topographic gastric specimens to test for H. pylori infection and its
      related histological features, translated into the operative link on gastritis
      assessment (OLGA), operative link on gastric intestinal metaplasia assessment
      (OLGIM) stages, and the presence of CGI. Spasmolytic polypeptide-expressing
      metaplasia (SPEM) was assessed by immunohistochemistry staining of trefoil factor
      2. RESULTS: Gastric cancer patients had higher prevalence of CGI and OLGIM stage
      II-IV, but not OLGA stage II-IV, than the controls (P = 0.001, OR = 3.4[95% CI:
      1.4-8.1] for CGI; OR = 5.0[95% CI: 2.0-12.8] for OLGIM). In patients with the
      combined presence of CGI and OLGIM stage II-IV, the risk of gastric cancer
      increased to 9.8 (P < 0.001). The first-degree relatives of the gastric cancer
      patients had a higher rate of the presence of CGI, but not OLGA or OLGIM stage II
      IV than the duodenal ulcer controls (P = 0.001). Of the first-degree relatives,
      the presence of CGI increased the risk of SPEM (P = 0.003, OR = 5.5[95% CI: 1.8
      17.0]). CONCLUSION: The corpus-predominant gastritis index, which is highly
      correlated to SPEM, may serve as an early marker to identify the H. pylori
      infected patients at a higher risk of gastric cancer.

PMID- 23550596
TI  - alpha-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor
      gamma to ameliorate experimental autoimmune encephalomyelitis in mice.
AB  - ALA (alpha-lipoic acid) is a natural, endogenous antioxidant that acts as a PPAR
      gamma (peroxisome-proliferator-activated receptor-gamma) agonist to counteract
      oxidative stress. Thus far, the antioxidative and immunomodulatory effects of ALA
      on EAE (experimental autoimmune encephalomyelitis) are not well understood. In
      this study, we found that ALA restricts the infiltration of inflammatory cells
      into the CNS (central nervous system) in MOG (myelin oligodendrocyte
      glycoprotein)-EAE mice, thus reducing the disease severity. In addition, we
      revealed that ALA significantly suppresses the number and percentage of
      encephalitogenic Th1 and Th17 cells and increases splenic Treg-cells (regulatory
      T-cells). Strikingly, we further demonstrated that ALA induces endogenous PPAR
      gamma centrally and peripherally but has no effect on HO-1 (haem oxygenase 1).
      Together, these data suggest that ALA can up-regulate endogenous systemic and
      central PPAR-gamma and enhance systemic Treg-cells to inhibit the inflammatory
      response and ameliorate MOG-EAE. In conclusion, our data provide the first
      evidence that ALA can augment the production of PPAR-gamma in vivo and modulate
      adaptive immunity both centrally and peripherally in EAE and may reveal further
      antioxidative and immunomodulatory mechanisms for the application of ALA in human
      MS (multiple sclerosis).

PMID- 23550597
TI  - Morphological segmentation of FIB-SEM data of highly porous media.
AB  - Nanoporous materials play an important role in modern batteries as well as fuel
      cells. The materials microstructure needs to be analyzed as it determines the
      electrochemical properties. However, the microstructure is too fine to be
      resolved by microcomputed tomography. The method of choice to analyze the
      microstructure is focused ion beam nanotomography (FIB-SEM). However, the
      reconstruction of the porous 3D microstructure from FIB-SEM image data in general
      has been an unsolved problem so far. In this paper, we present a new method using
      morphological operations. First, features are extracted from the data.
      Subsequently, these features are combined to an initial segmentation, that is
      then refined by a constrained watershed transformation. We evaluate our method
      with synthetic data, generated by a simulation of the FIB-SEM imaging process. We
      compare the ground truth in the simulated data to the segmentation result. The
      new method is found to produce a much smaller error than existing techniques.

PMID- 23550598
TI  - Patterns of functioning in older adults with mild cognitive impairment: a two
      year study focusing on everyday technology use.
AB  - OBJECTIVES: Early detection is vital for persons with mild cognitive impairment
      (MCI) who are at risk of activity and participation limitations, and
      crosssectional studies suggest the ability to use everyday technology (ET) to be
      a sensible tool. However, group level analyses fail to inform us about how
      functioning can vary over time for individuals. This study aimed at exploring and
      describing patterns of functioning over two years in a sample newly classified
      with MCI, with a special focus on perceived difficulty in ET use and involvement
      in everyday activities. In addition, cognitive functioning and conversion to
      dementia were studied. METHOD: 37 older adults (aged >= 55) with MCI were
      assessed at inclusion, and at 6, 12, and 24 months. Longitudinal case plots for
      the variables under study were analyzed based on strict criteria using a person
      oriented approach. Paired t-tests from baseline and 24 months were also conducted
      to analyze change. RESULTS: The 32 participants who remained in the study after
      two years showed three distinct patterns of functioning over time:
      stable/ascending (n = 10), fluctuating (n = 10), and descending (n = 12), with
      the highest conversion to dementia in the descending pattern (58%). The perceived
      ability to use ET decreased or fluctuated in 50% of the sample. However, on a
      group level, a significant difference between baseline and 24 months was found
      only regarding cognitive function. CONCLUSION: As the need for support is
      individual and likely to alter over time, repeated evaluations of activity
      involvement and difficulty in ET use are suggested to target timely interventions
      for persons with MCI.

PMID- 23550599
TI  - Half empty or half full? New York's soda rule in historical perspective.

PMID- 23550600
TI  - Limiting "sugary drinks" to reduce obesity--who decides?

PMID- 23550601
TI  - Pneumonia from human coronavirus in a macaque model.

PMID- 23550602
TI  - Model of the deposition of aerosol particles in the respiratory tract of the rat.
      II. Hygroscopic particle deposition.
AB  - BACKGROUND: Rats are frequently used to study the pharmacological and
      toxicological effects of inhaled aerosol particles. The deposition behavior of
      aerosol particles in airways is affected by their hygroscopic properties, which
      accordingly influence the results of such studies. METHOD: A recently published
      nonhygroscopic aerosol particle deposition model for rat airways was extended
      with equations for hygroscopic particle growth in humid air and with a model to
      mimic the temperature and relative humidity conditions in the rat airways
      transformed from the upper human airways. As there are no experimental data
      available for hygroscopic deposition in rat lungs, several model assumptions were
      made for the humidity distribution in the upper rat airways. RESULTS: The total
      and regional deposition probability of salt particles in the diameter range 0.02
      to 5 MUm in rat lung was significantly changed by the hygroscopic properties. The
      maximum ratios of the total deposition of inhaled initially dry sodium chloride,
      cobalt chloride, and zinc sulfate particles compared with nonhygroscopic
      particles were 3.28, 2.44, and 2.13, respectively, and the minimum ratios 0.57,
      0.63, and 0.70, respectively. The corresponding maximum (and minimum) ratios for
      the hygroscopic drugs histamine dihydrochloride, carbenicillin disodium, and
      atropine sulfate were 1.86 (0.65), 1.53 (0.70), and 1.35 (0.76), respectively.
      Total deposition was about 20% higher in human airways than in rat airways. The
      flow regime in the rat upper airways influenced total and regional deposition
      much less than it did in human airways. CONCLUSION: The hygroscopicity of salt
      and drug aerosol particles is an important factor in rat lung deposition.

PMID- 23550603
TI  - Response.

PMID- 23550604
TI  - Lipoprotein lipase in aortic valve stenosis is associated with lipid retention
      and remodelling.
AB  - BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic disorder
      characterized by a fibrocalcific remodelling. It is suspected that lipid
      retention within the aortic valve may be one important mechanism participating to
      aortic valve remodelling. Lipoprotein lipase (LPL) is implicated in lipid
      metabolism and may play a role in lipid retention within the aortic valve.
      METHODS: In 57 patients, CAVD were analysed for the expression of LPL by q-PCR
      and immunohistochemistry. Expression of oxidized-LDL (ox-LDL) and decorin was
      also documented. In addition, a complete blood profile, including the size of LDL
      and high-density lipoprotein (HDL) particles, were performed to find associations
      between the blood lipid profile and expression of ox-LDL and LPL within CAVD.
      RESULTS: Immunohistochemistry studies revealed that LPL was expressed in stenotic
      aortic valves as a diffuse staining and also in dense cellular areas where
      macrophages were abundant. Expression of LPL co-localized with decorin and ox
      LDL. In turn, valves with higher amount of ox-LDL had elevated number of LPL
      transcripts. In addition, we documented that the small, dense HDL phenotype was
      associated with an elevated amount of ox-LDL and LPL transcripts within CAVD.
      Furthermore, expression of LPL was associated with several indices of
      fibrocalcific remodelling of the aortic valve. CONCLUSION: Expression of LPL
      within CAVD is related to the amount of ox-LDL, which is, in turn, associated
      with the small, dense HDL phenotype. Lipid retention associated with smaller HDL
      particles may participate in the expression of LPL, whereby a fibrocalcific
      remodelling of the aortic valve is promoted.

PMID- 23550605
TI  - Frequent detection of cytomegalovirus and Epstein-Barr virus in cervical
      secretions from healthy young women.
AB  - OBJECTIVE: To investigate asymptomatic shedding from the uterine cervix of five
      human herpes viruses: cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes
      simplex virus (HSV) type 1 and type 2 and varicella zoster virus (VZV), in young
      women. DESIGN: A descriptive study. SETTING: Sahlgrenska University Hospital.
      POPULATION: Three hundred and five young, healthy Swedish women. METHODS:
      Cervical specimens were analyzed for the presence of viral DNA with a
      quantitative real-time PCR assay. MAIN OUTCOME MEASURES: Detection of viral DNA.
      RESULTS: Viral DNA was detected in 66 (21.6%) of the cervical samples. The most
      common findings were CMV DNA, detected in 35 (11.5%), and EBV DNA, found in 32
      (10.5%) of the women. HSV-1 DNA was detected in 5 (1.7%) and HSV-2 DNA in 4
      (1.4%), but VZV DNA was not found. The estimated DNA level for the detected
      viruses was similar with a mean DNA quantity of 2.6 log genome equivalents
      (Geq)/mL for CMV (range 1.7-4.3), 2.5 log Geq/mL for EBV (range 1.7-4.7), 2.4 log
      Geq/mL for HSV-1 (range 1.7-3.5) and 2.6 log Geq/mL for HSV-2 (range 1.7-4.1).
      The simultaneous presence of DNA from two or more herpes viruses was detected in
      eight specimens. CONCLUSIONS: Asymptomatic shedding of CMV and EBV from the
      uterine cervix was found in one-fifth of young women. In four of the cervical
      samples; two with EBV, one with CMV, one with HSV-2, high amounts of viral DNA
      (>4 log Geq/mL) were detected suggesting a greater risk of transmitting the virus
      perinatally or sexually.

PMID- 23550607
TI  - Gene loss, thermogenesis, and the origin of birds.
AB  - Compared to related taxa, birds have exceptionally enlarged and diversified
      skeletal muscles, features that are closely associated with skeletal
      diversification and are commonly explained by a diversity of avian ecological
      niches and locomotion types. The thermogenic muscle hypothesis (TMH) for the
      origin of birds proposes that such muscle hyperplasia and the associated skeletal
      innovations are instead the consequence of the avian clade originating from an
      ancestral population that underwent several successive episodes of loss of genes
      associated with thermogenesis, myogenesis, and skeletogenesis. Direct bird
      ancestors met this challenge with a combination of behavioral strategies (e.g.,
      brooding of nestlings) and acquisition of a variety of adaptations for enhanced
      nonshivering thermogenesis in skeletal muscle. The latter include specific
      biochemical alterations promoting muscle heat generation and dramatic expansion
      of thigh and breast muscle mass. The TMH proposes that such muscle hyperplasia
      facilitated bipedality, freeing upper limbs for new functions (e.g., flight,
      swimming), and, by altering the mechanical environment of embryonic development,
      generated skeletal novelties, sometimes abruptly, that became distinctive
      features of the avian body plan.

PMID- 23550608
TI  - Computer-aided sperm analysis: past, present and future.
AB  - Computer-aided sperm analysis (CASA) system has been accepted and used commonly
      as a routine semen analysis instrument in hospital clinical laboratories
      worldwide. However, technicians in clinical laboratories have little informed
      knowledge about the principles of CASA system and the sources of analysis errors.
      In this review, we focus on the concept of CASA, the development course of CASA
      technology, the clinical application of CASA systems and the factors influencing
      the accuracies of results, such as frame rate, sperm counting chambers affiliated
      to the CASA system, algorithms and sperm concentration. These factors and lack of
      internal quality control may result in huge errors of the CASA between systems
      and laboratories. It is therefore necessary to perform the standardisation and
      quality control for CASA. 

PMID- 23550609
TI  - Advances in brain drug targeting and delivery: limitations and challenges of
      solid lipid nanoparticles.
AB  - INTRODUCTION: With the advancement in the field of medical colloids and
      interfacial sciences, the life expectancy has been greatly improved. In addition,
      changes in the human lifestyle resulted in development of various organic and
      functional disorders. Central nervous system (CNS) disorders are most prevalent
      and increasing among population worldwide. The neurological disorders are multi
      systemic and difficult to treat as portal entry to brain is restricted on account
      of its anatomical and physiological barrier. AREAS COVERED: The present review
      discusses the limitations to CNS drug delivery, and the various approaches to
      bypass the blood brain barrier (BBB), focusing on the potential use of solid
      lipid nanoparticles (SLN) for drug targeting to brain. The methods currently in
      use for SLN production, physicochemical characterization and critical issues
      related to the formulation development suitable for targeting brain are also
      discussed. EXPERT OPINION: The potential advantages of the use of SLN over
      polymeric nanoparticles are due to their lower cytotoxicity, higher drug loading
      capacity and scalability. In addition, their production is cost effective and the
      systems provide a drug release in a controlled manner up to several weeks. Drug
      targeting potential of SLN can be enhanced by attaching ligands to their surface.

PMID- 23550610
TI  - Prevention and therapy of alcohol withdrawal on intensive care units: systematic
      review of controlled trials.
AB  - BACKGROUND: Alcohol withdrawal syndrome (AWS) occurs in 16 to 31% of intensive
      care unit (ICU) patients after cessation of sedation. There exist many preventive
      and therapeutic strategies, but no systematic review (SR) has been published on
      this topic so far. We aimed to perform a synopsis of all controlled trials of AWS
      prevention and therapy in ICU published between 1971 and 30 March 2011 following
      the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA)
      statement. METHODS: We performed a MEDLINE search with the terms "alcohol" AND
      "ICU" as well as "alcohol withdrawal" AND "intensive care." All publications that
      matched our eligibility criteria were analyzed according to our predefined
      criteria. RESULTS: We identified 6 controlled trials about AWS prevention and 8
      about AWS therapy in ICUs. For AWS prevention, benzodiazepines (BZO), ethanol
      (EtOH), and clonidine were evaluated as single agents, and BZO, clonidine,
      clomethiazol and haloperidol were studied in drug combinations. All evaluated
      single agents and combinations were found to be effective for AWS prevention.
      Clomethiazol was found to be associated with a higher tracheobronchitis rate and
      thus disadvised for critically ill patients. For AWS therapy, BZO, gamma
      hydroxybutyric acid (GHB), and clomethiazol were evaluated in randomized
      controlled trials as single agents and phenobarbital, clonidine, and haloperidol
      as adjuncts. All evaluated regimens were found to be effective for AWS therapy.
      Overall, in the ICU, BZO were found to be superior to GHB and clomethiazol
      regarding safety and efficacy. Furthermore, 4 cohort trials with historical
      control groups evaluated the effect of the implementation of a standardized
      protocol of BZO therapy for AWS in ICUs. All of these 4 studies found better
      outcome for the intervention groups. CONCLUSIONS: Based on the evidence of this
      SR, EtOH or BZO can be advised for AWS prevention on ICU patients with alcohol
      dependence, but EtOH is not allowed for therapy of AWS. AWS therapy should be
      standardized and based on symptom-triggered BZO administration. Alpha2-agonists
      and haloperidol should be added for autonomic and productive psychotic symptoms.

PMID- 23550611
TI  - Quantifying the effect of habitat availability on species distributions.
AB  - 1. If animals moved randomly in space, the use of different habitats would be
      proportional to their availability. Hence, deviations from proportionality
      between use and availability are considered the tell-tale sign of preference.
      This principle forms the basis for most habitat selection and species
      distribution models fitted to use-availability or count data (e.g. MaxEnt and
      Resource Selection Functions). 2. Yet, once an essential habitat type is
      sufficiently abundant to meet an individual's needs, increased availability of
      this habitat type may lead to a decrease in the use/availability ratio.
      Accordingly, habitat selection functions may estimate negative coefficients when
      habitats are superabundant, incorrectly suggesting an apparent avoidance.
      Furthermore, not accounting for the effects of availability on habitat use may
      lead to poor predictions, particularly when applied to habitats that differ
      considerably from those for which data have been collected. 3. Using simulations,
      we show that habitat use varies non-linearly with habitat availability, even when
      individuals follow simple movement rules to acquire food and avoid risk. The
      results show that the impact of availability strongly depends on the type of
      habitat (e.g. whether it is essential or substitutable) and how it interacts with
      the distribution and availability of other habitats. 4. We demonstrate the
      utility of a variety of existing and new methods that enable the influence of
      habitat availability to be explicitly estimated. Models that allow for non-linear
      effects (using b-spline smoothers) and interactions between environmental
      covariates defining habitats and measures of their availability were best able to
      capture simulated patterns of habitat use across a range of environments. 5. An
      appealing aspect of some of the methods we discuss is that the relative influence
      of availability is not defined a priori, but directly estimated by the model.
      This feature is likely to improve model prediction, hint at the mechanism of
      habitat selection, and may signpost habitats that are critical for the organism's
      fitness.

PMID- 23550612
TI  - Nail psoriasis: a questionnaire-based survey.
AB  - BACKGROUND: Skin manifestations are the most characteristic finding of psoriasis.
      However, nail involvement is also a clinical feature of disease although it is
      often overlooked. The documented prevalence of nail psoriasis varies between
      10.0% and 81.1%. OBJECTIVES: The aim of this investigation is to gain knowledge
      about the prevalence and clinical manifestations of nail psoriasis and patient
      experiences of treatment of nail psoriasis. METHODS: A structured, self
      administered questionnaire was distributed to all members (n = 5400) of the Dutch
      Psoriasis Association. The questionnaire enquired about sociodemographic patient
      characteristics, disease-related data and treatment of nail psoriasis. Patients
      reported their nail manifestations with photographs after instruction. Patients
      with nail psoriasis were compared with patients without nail psoriasis. RESULTS:
      A response rate of 27% was achieved. The prevalence of nail psoriasis was 66.0%.
      The most frequently observed psoriatic nail manifestation was pitting (65.4%),
      whereas red spots in the lunula were infrequently seen (6.5%). Patients with nail
      psoriasis more frequently stated psoriasis capitis (75.8% vs. 65.7%), genital
      psoriasis (32.7% vs. 20.3%) and psoriatic arthritis (46.4% vs. 30.6%) compared
      with patients with psoriasis without nail involvement. Only 16.0% of patients
      received treatment for nail psoriasis. Systemic therapies were most frequently
      stated as being effective for nail lesions. CONCLUSIONS: Nail manifestations seem
      to be more prevalent in patients with psoriasis than previously thought. In
      addition, nail psoriasis is shown to be associated with widespread and more
      severe forms of psoriasis, and different treatment options are experienced as
      being effective for nail psoriasis. Notwithstanding, nail psoriasis is still an
      often overlooked feature of the disease.

PMID- 23550613
TI  - Ultrafast excited-state proton transfer to the solvent occurs on a hundred
      femtosecond time-scale.
AB  - Steady-state and ultrafast time-resolved techniques were used to study a newly
      synthesized photoacid, phenol-carboxyether dipicolinium cyanine dye, QCy9. We
      found that the excited-state proton transfer (ESPT) to water occurs at the
      remarkably short time of about 100 fs, k(PT) ~ 1 * 10(13) s(-1), the fastest rate
      reported up to now. On the basis of the Forster-cycle, the pK(a)* value is
      estimated to be -8.5 +/- 0.4. In previous studies, we reported the photoacidity
      of another superphotoacid, the QCy7 for which we found an ESPT rate constant of
      ~1.25 * 10(12) s(-1), one-eighth that of the QCy9 compound. We found a kinetic
      isotope effect of the ESPT of about two.

PMID- 23550614
TI  - Synthesis of 2(1H)-quinolinones via Pd-catalyzed oxidative cyclocarbonylation of
      2-vinylanilines.
AB  - Palladium-catalyzed oxidative cyclocarbonylation of N-monosubstituted-2
      vinylanilines constitutes a simple, direct, and selective method for the
      synthesis of 2(1H)-quinolinones. The reaction conditions are attractive in terms
      of environmental considerations and operational simplicity. 2(1H)-Quinolinones
      with a variety of functional groups were prepared in up to 97% yield.

PMID- 23550615
TI  - ABSCISIC ACID INSENSITIVE3 regulates abscisic acid-responsive gene expression
      with the nuclear factor Y complex through the ACTT-core element in Physcomitrella
      patens.
AB  - The phytohormone ABA and the transcription factor ABSCISIC ACID INSENSITIVE 3
      (ABI3)/VIVIPAROUS 1 (VP1) function in protecting embryos during the desiccation
      stage of seed development. In a similar signaling pathway, vegetative tissue of
      the moss Physcomitrella patens survives desiccation by activating downstream
      genes (e.g. LEA1) in response to ABA and ABI3. We show that the PpLEA1 promoter
      responds to PpABI3 primarily through the ACTT-core element (5'-TCCACTTGTC-3'),
      while the ACGT-core ABA-responsive element (ABRE) appears to respond to ABA
      alone. We also found by yeast-two-hybrid screening that PpABI3A interacts with
      PpNF-YC1, a subunit of CCAAT box binding factor (CBF)/nuclear factor Y (NF-Y).
      PpNF-YC1 increased the activation of the PpLEA1 promoter when incubated with
      PpABI3A, as did NF-YB, NF-YC, and ABI3 from Arabidopsis. This new response
      element (ACTT) is responsible for activating the ABI3-dependent ABA response
      pathway cooperatively with the nuclear factor Y (NF-Y) complex. These results
      further define the regulatory interactions at the transcriptional level for the
      expression of this network of genes required for drought/desiccation tolerance.
      This gene regulatory set is in large part conserved between vegetative tissue of
      bryophytes and seeds of angiosperms and will shed light on the evolution of this
      pathway in the green plant lineage.

PMID- 23550616
TI  - An automatic vision-based malaria diagnosis system.
AB  - Malaria is a worldwide health problem with 225 million infections each year. A
      fast and easy-to-use method, with high performance is required to differentiate
      malaria from non-malarial fevers. Manual examination of blood smears is currently
      the gold standard, but it is time-consuming, labour-intensive, requires skilled
      microscopists and the sensitivity of the method depends heavily on the skills of
      the microscopist. We propose an easy-to-use, quantitative cartridge-scanner
      system for vision-based malaria diagnosis, focusing on low malaria parasite
      densities. We have used special finger-prick cartridges filled with acridine
      orange to obtain a thin blood film and a dedicated scanner to image the
      cartridge. Using supervised learning, we have built a Plasmodium falciparum
      detector. A two-step approach was used to first segment potentially interesting
      areas, which are then analysed in more detail. The performance of the detector
      was validated using 5,420 manually annotated parasite images from malaria
      parasite culture in medium, as well as using 40 cartridges of 11,780 images
      containing healthy blood. From finger prick to result, the prototype cartridge
      scanner system gave a quantitative diagnosis in 16 min, of which only 1 min
      required manual interaction of basic operations. It does not require a wet lab or
      a skilled operator and provides parasite images for manual review and quality
      control. In healthy samples, the image analysis part of the system achieved an
      overall specificity of 99.999978% at the level of (infected) red blood cells,
      resulting in at most seven false positives per microlitre. Furthermore, the
      system showed a sensitivity of 75% at the cell level, enabling the detection of
      low parasite densities in a fast and easy-to-use manner. A field trial in
      Chittagong (Bangladesh) indicated that future work should primarily focus on
      improving the filling process of the cartridge and the focus control part of the
      scanner.

PMID- 23550617
TI  - Optogenetic manipulation of neural and non-neural functions.
AB  - Optogenetic manipulation of the neuronal activity enables one to analyze the
      neuronal network both in vivo and in vitro with precise spatio-temporal
      resolution. Channelrhodopsins (ChRs) are light-sensitive cation channels that
      depolarize the cell membrane, whereas halorhodopsins and archaerhodopsins are
      light-sensitive Cl(-) and H(+) transporters, respectively, that hyperpolarize it
      when exogenously expressed. The cause-effect relationship between a neuron and
      its function in the brain is thus bi-directionally investigated with evidence of
      necessity and sufficiency. In this review we discuss the potential of
      optogenetics with a focus on three major requirements for its application: (i)
      selection of the light-sensitive proteins optimal for optogenetic investigation,
      (ii) targeted expression of these selected proteins in a specific group of
      neurons, and (iii) targeted irradiation with high spatiotemporal resolution. We
      also discuss recent progress in the application of optogenetics to studies of non
      neural cells such as glial cells, cardiac and skeletal myocytes. In combination
      with stem cell technology, optogenetics may be key to successful research using
      embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) derived
      from human patients through optical regulation of differentiation-maturation,
      through optical manipulation of tissue transplants and, furthermore, through
      facilitating survival and integration of transplants.

PMID- 23550618
TI  - National rates of Helicobacter pylori recurrence are significantly and inversely
      correlated with human development index.
AB  - BACKGROUND: Helicobacter pylori infection is a worldwide threat to human health
      with recurrence rates that vary widely. The precise correlation between H. pylori
      recurrence and socioeconomic development has not been determined. AIM: To
      determine H. pylori recurrence rates after successful eradication and their
      association with socioeconomic development metrics. METHODS: Bibliographical
      searches were performed in the MEDLINE database. We reviewed all results,
      filtered by inclusion criteria, extracted primary results to calculate H. pylori
      recurrence rates and calculated national Human Development Index (HDI) values for
      the periods during which the studies were conducted. RESULTS: One thousand two
      hundred and twenty six cases of H. pylori recurrence in 77 eligible studies were
      observed in 43 525.1 follow-up patient-years after successful eradication
      therapy, giving a recurrence rate of 2.82 +/- 1.16% per patient-year (weighted
      mean +/- 95% confidence interval). H. pylori recurrence rate was inversely
      correlated with national HDI on linear (r = -0.633) and weighted least square (r
      = -0.546) regression analysis. Countries with very high HDI had a mean recurrence
      rate significantly lower than that of high, medium and low HDI countries (P <
      0.01, 0.001, and 0.001, respectively). CONCLUSIONS: Less-developed areas, as
      measured by HDI, are more likely to have high H. pylori recurrence rates. A
      different approach to follow-up after H. pylori eradication is needed in
      developing countries where reinfection is highly prevalent, paying special
      attention to sources of reinfection and high-risk groups.

PMID- 23550619
TI  - The quantitation of cocaine on U.S. currency: survey and significance of the
      levels of contamination.
AB  - It has long been suspected that the illicit distribution of cocaine in the United
      States has led to a large-scale contamination of the currency supply. To
      investigate the extent of contamination, 418 currency samples (4174 bills) were
      collected from 90 locations around the United States from 1993 to 2009. The
      extent of their cocaine contamination was quantitated via gas chromatography/mass
      spectrometry or liquid chromatography/mass spectrometry. The level of cocaine
      contamination was determined to average 2.34 ng/bill across all denominations
      ($1, $5, $10, $20, $50, and $100). Levels of cocaine contamination on currency
      submitted to the Federal Bureau of Investigation Laboratory in criminal cases
      over the 1993-2001 timeframe had significantly higher contamination than currency
      in general circulation. A mathematical model was developed based on the
      background survey that indicates the likelihood of drawing a bill in specific
      concentration ranges. For example, there is a 0.8349 likelihood that random bill
      will have contamination less than 20 ng.

PMID- 23550622
TI  - Sperm motility and DNA integrity affected by different g-forces in the
      preparation of sperm in urine specimens.
AB  - Retrograde ejaculation, a common type of anejaculation, is attributable to many
      causes, some of which can be treated with medication and some of which cannot.
      For infertility treatment, sperm must be collected from the urine of the
      patients. Our study attempts to ascertain the effects of different g-forces on
      sperm motility, morphology and DNA integrity in sperm preparation by the Sil
      SelectTM density gradient method of isolating sperm from urine specimens. Forty
      seven semen samples with normal semen analyses according to World Health
      Organisation (WHO) 1999 criteria were included in this study. Semen samples of 1
      ml were mixed with 20 ml alkalinised normal urine and then divided equally into
      tubes A and B. The two samples were prepared by the Sil-SelectTM density gradient
      centrifugation method at 350 g (tube A) and at 700 g (tube B). Total motile sperm
      after centrifugation at 700 g was significantly higher than after centrifugation
      at 350 g [6.7 (0.4-23.0) million versus 3.1 (0.1-13.7) million] (P < 0.001).
      There was no significant difference between the either the percentage of sperm
      with normal morphology or with DNA damage between centrifugation at 350 g and 700
      g (P > 0.05), although centrifugation at 700 g achieves a higher number of total
      motile sperm compared with Sil-SelectTM sperm preparation at 350 g
      centrifugation. 

PMID- 23550623
TI  - Femoral head abrasion during reduction of micro THR.

PMID- 23550624
TI  - Perceived control as a longitudinal moderator of late-life stressors on
      depressive symptoms.
AB  - OBJECTIVES: This study examined perceived control as a moderator of the
      relationship between late-life stressors and depressive symptoms among a sample
      of older New Zealanders. METHOD: Data were drawn from a longitudinal study with
      two data collection periods, one year apart. The Time 1 sample consisted of 1489
      participants ranging in age from 65 to 94 years and 72% percent participated at
      Time 2. Correlational and multiple regression procedures were used to examine
      study hypotheses. RESULTS: Results showed that Time 1 perceived control beliefs
      were a unique predictor of depressive symptoms at Time 2 after controlling for
      Time 1 depressives symptoms and other relevant variables. Further, perceived
      control beliefs at Time 1 moderated the relationship between late-life stressors
      and depressive symptoms at Time 2. Those with low perceived control demonstrated
      a stronger relationship between late-life stressors and depressive symptoms than
      those with high perceived control. CONCLUSION: This study provides evidence that
      perceived control influences levels of depressive symptoms over time among older
      adults. Results also support the hypothesis that control beliefs moderate the
      relationship between late-life stressors and depressive symptoms among older
      adults. Implications include attributional retraining to promote perceived
      control and subsequent well-being in older adults.

PMID- 23550625
TI  - Activation of PPARgamma by pioglitazone potentiates the effects of naltrexone on
      alcohol drinking and relapse in msP rats.
AB  - BACKGROUND: Pioglitazone is a selective peroxisome proliferator-activated
      receptor gamma (PPARgamma) agonist used for the treatment of insulin resistance
      and type 2 diabetes. Previous studies conducted in our laboratory showed that
      activation of PPARgamma by pioglitazone reduces alcohol drinking, stress-induced
      relapse, and alcohol withdrawal syndrome in rats. Pioglitazone was not able to
      prevent relapse elicited by alcohol cues. Conversely, the nonselective opioid
      antagonist naltrexone has been shown to reduce alcohol drinking and cue- but not
      stress-induced relapse in rodents. METHODS: Based on these findings, this study
      was sought to determine the efficacy of pioglitazone and naltrexone combination
      on alcohol intake and relapse behavior. Genetically selected alcohol-preferring
      Marchigian Sardinian (msP) rats were used for the study. RESULTS: Pioglitazone
      (10 and 30 mg/kg) and naltrexone (0.25 and 1.0 mg/kg) each individually reduced
      alcohol drinking in msP rats. The combination of the 2 drugs resulted in a more
      potent alcohol drinking reduction than single agents. Confirming previous
      studies, pioglitazone (10 and 30 mg/kg) significantly reduced relapse induced by
      the pharmacological stressor yohimbine (1.25 mg/kg) but not by cues predictive of
      alcohol availability. Conversely, naltrexone reduced reinstatement of drug
      seeking elicited by alcohol cues but not by yohimbine. CONCLUSIONS: The drug
      combination was effective in reducing both relapse behaviors. These findings open
      new vistas in the use pioglitazone in combination with naltrexone for the
      treatment of alcoholism.

PMID- 23550626
TI  - Decreased Nox4 levels in the myocardium of patients with aortic valve stenosis.
AB  - The NADPH oxidases are a key family of ROS (reactive oxygen species)-producing
      enzymes which may differentially contribute to cardiac pathophysiology. Animal
      studies show uncertain results regarding the regulation of cardiac Nox4 by
      pressure overload and no data are available on human myocardial Nox4. In the
      present study, we evaluated Nox4 expression and its relationship with myocardial
      remodelling and LV (left ventricular) function in patients with severe AS (aortic
      valve stenosis). Endomyocardial biopsies from 34 patients with AS were obtained
      during aortic valve replacement surgery. LV morphology and function were assessed
      by echocardiography. Myocardial samples from subjects deceased of non-CVDs
      (cardiovascular diseases) were analysed as controls. Nox4 localization was
      evaluated by immunohistochemistry and quantified by Western blot. Myocardial
      capillary density, fibrosis and cardiomyocyte dimensions and apoptosis were
      assessed histologically to evaluate myocardial remodelling. Nox4 was present in
      samples from all subjects and expressed in cardiomyocytes, VSMCs (vascular smooth
      muscle cells), endothelium and fibroblasts. Nox4 levels were reduced 5-fold in AS
      patients compared with controls (P<0.01). Nox4 levels directly correlated with
      cardiomyocyte cross-sectional area (r=0.299, P<0.05) and diameter (r=0.406,
      P<0.05) and capillary density (r=0.389, P<0.05), and inversely with cardiomyocyte
      apoptosis (r=-0.316, P<0.05) in AS patients. In addition, Nox4 levels correlated
      with echocardiographic parameters (LV ejection fraction: r=0.353, P<0.05; midwall
      fractional shortening: r=0.355, P<0.05; deceleration time: r=-0.345, P<0.05) in
      AS patients. Nox4 is expressed in human myocardium and reduced in AS patients.
      The observed associations of Nox4 with cardiomyocyte parameters and capillary
      density in AS patients suggest a potential role of Nox4 deficiency in the
      myocardial remodelling present in the human pressure-overloaded heart.

PMID- 23550627
TI  - Human formalin-fixed paraffin-embedded tissues: an untapped specimen for
      biomonitoring of carcinogen DNA adducts by mass spectrometry.
AB  - DNA adducts represent internal dosimeters to measure exposure to environmental
      and endogenous genotoxicants. Unfortunately, in molecular epidemiologic studies,
      measurements of DNA adducts often are precluded by the unavailability of fresh
      tissue. In contrast, formalin-fixed paraffin embedded (FFPE) tissues frequently
      are accessible for biomarker discovery. We report here that DNA adducts of
      aristolochic acids (AAs) can be measured in FFPE tissues at a level of
      sensitivity comparable to freshly frozen tissue. AAs are nephrotoxic and
      carcinogenic compounds found in Aristolochia herbaceous plants, many of which
      have been used worldwide for medicinal purposes. AAs are implicated in the
      etiology of aristolochic acid nephropathy and upper urinary tract carcinoma. 8
      Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxole-5-carboxylic acid (AA-I) is a
      component of Aristolochia herbs and a potent human urothelial carcinogen. AA-I
      reacts with DNA to form the aristolactam (AL-I)-DNA adduct 7-(deoxyadenosin-N(6)
      yl) aristolactam I (dA-AL-I). We established a method to quantitatively retrieve
      dA-AL-I from FFPE tissue. Adducts were measured, using ultraperformance liquid
      chromatography/mass spectrometry, in liver and kidney tissues of mice exposed to
      AA-I, at doses ranging from 0.001 to 1 mg/kg body weight. dA-AL-I was then
      measured in 10-MUm thick tissue-sections of FFPE kidney from patients with upper
      urinary tract cancers; the values were comparable to those observed in fresh
      frozen samples. The limit of quantification of dA-AL-I was 3 adducts per 10(9)
      DNA bases per 2.5 MUg of DNA. The ability to retrospectively analyze FFPE tissues
      for DNA adducts may provide clues to the origin of human cancers for which an
      environmental cause is suspected. 

PMID- 23550628
TI  - Cross-sectional assessment of the roles of comorbidities in resting and activity
      related dyspnea in severely obese women.
AB  - OBJECTIVES: Obesity has been associated with a lesser degree of asthma control
      that may be biased by other comorbidities. The objectives of this cross-sectional
      study were to describe resting and activity-related dyspnea complaints according
      to the presence of obesity-related comorbidities (asymptomatic airway
      hyperresponsiveness (AHR), asthma, gastroesophageal reflux disease (GERD) and
      sleep-disordered breathing (SDB)). We hypothesized that obese women can exhibit
      both resting and activity-related dyspnea, independently of the presence of
      asthma. METHODS: Severely obese (body mass index (BMI) > 35 kg m(-2)) women
      prospectively underwent description of resting and activity-related dyspnea
      (verbal descriptors and Medical Research Council (MRC) scale), pulmonary function
      testing (spirometry, absolute lung volumes, and methacholine challenge test),
      oesogastro-duodenal fibroscopy, and overnight polygraphy. Thirty healthy lean
      women without airway hyperresponsiveness were enrolled. RESULTS: Resting dyspnea
      complaints were significantly more prevalent in obesity (prevalence 41%) than in
      healthy lean women (prevalence 3%). Chest tightness and the need for deep
      inspirations were independently associated with both asthma and GERD while
      wheezing and cough were related to asthma only in obese women. Activity-related
      dyspnea was very prevalent (MRC score > 1, 75%), associated with obesity, with
      the exception of wheezing on exertion due to asthma. Asymptomatic AHR and SDB did
      not affect dyspneic complaints. CONCLUSIONS: In severely obese women referred for
      bariatric surgery, resting dyspnea complaints are observed in association with
      asthma or GERD, while activity-related dyspnea was mainly related to obesity
      only. Consequently, asthma does not explain all respiratory complaints of obese
      women.

PMID- 23550629
TI  - Heritability and sibling recurrent risk of developmental dysplasia of the hip in
      Chinese population.
AB  - BACKGROUND: Previous familial segregation studies supported that developmental
      dysplasia of the hip (DDH) is a multifactorial genetic disease. However, the
      exact extent of genetic effects has not been fully evaluated, especially in Asian
      population. The aim of this study is to estimate the sibling recurrent risk and
      heritability of DDH in a large Chinese cohort. MATERIALS AND METHODS: Four
      hundred and twenty-nine DDH probands and 534 matched normal controls were
      recruited from a screening programme for DDH, including 628 siblings in families
      of probands and 889 siblings in those of controls, respectively. The detailed
      information of family history was obtained, and the prevalence of DDH among
      siblings of probands, as well as controls, was determined. The sibling recurrent
      risk and heritability was estimated using classical liability threshold model.
      RESULTS: Eighty-seven siblings (13.85%) in families of proband and 14 siblings
      (1.57%) in normal control families were diagnosed as DDH. The recurrent risk in
      siblings of probands was at least tenfolds that in siblings of controls. Compared
      with the normal controls, the sibling recurrent risk was about 12-fold increase
      in male sib, and 9-fold increase in female sib. Overall, a high heritability of
      83.59 +/- 4.90% (h(2) +/- SE) was observed. When stratified by genders, it was
      even higher for female siblings (91.02 +/- 7.25%). CONCLUSION: This study for the
      first time exhibits a high sibling recurrent risk and heritability for DDH in
      Asian population. It also shows there is a high probability to identify the
      underlying predisposition genes in future genetic study.

PMID- 23550630
TI  - Skin permeation behavior of elastic liposomes: role of formulation ingredients.
AB  - INTRODUCTION: With the incorporation of edge activators into the lipid bilayer
      structure, elasticity properties are given to liposomes. Regardless of the debate
      over the precise permeation mechanism of elastic liposomes, these vesicles have
      been proven to enhance drug permeation into or through skin in most cases. AREAS
      COVERED: This article provides an overview of the formulation ingredients of
      elastic liposomes and their relationship with skin permeation behavior. The
      ingredients are divided into two categories of basic and optional ingredients.
      The effect of stability on permeation behavior of the vesicles is highlighted.
      EXPERT OPINION: More attention should be paid to the stability of elastic
      liposomes. The different stability properties of the elastic liposomes following
      administration can induce different skin permeation behaviors of the vesicles. It
      is necessary to select the optimum composition of the elastic liposomes in order
      to control the stability and permeation behavior of the vesicles into or through
      the skin. Moreover, for the development of elastic liposomes, particular
      attention should also be paid to the drug leakage from the vesicles during long
      term storage. The application of optional ingredients to improve the stability
      and/or elasticity of the elastic liposomes is becoming a new trend.

PMID- 23550631
TI  - Indigenous knowledge systems and attitudes towards male infertility in Mhondoro
      Ngezi, Zimbabwe.
AB  - Male impotence and infertility are health and social problems that have resulted
      in significant suffering to men the world over. From an African perspective, and
      in Zimbabwe in particular, the taboo nature of male impotence and infertility
      carries a lot of mystique. Based on evidence from focus-group discussions, in
      depth and key-informant interviews, this study reveals rural Shona people to have
      indigenous knowledge systems that trigger the investigation of signs of impotence
      (perceived as associated with male infertility) at infancy, puberty and after
      marriage. Male infertility carries overtones of failure, frustration, pain,
      social ostracism, stigma, marital instability, discomfiture and suicide.
      Intervention strategies to remedy perceived problems were exclusively
      sociocultural, involving the administration of traditional herbs and traditional
      healers' divination. Given the existence of indigenous knowledge systems for the
      investigation and mediation of male impotence and infertility, it is worth
      incorporating traditional healers in future strategies targeting these
      emasculating conditions.

PMID- 23550632
TI  - Training health workers for magnesium sulfate use reduces case fatality from
      eclampsia: results from a multicenter trial.
AB  - OBJECTIVE: To investigate the effectiveness of an intervention aimed at improving
      the case management of eclampsia. DESIGN: A multi-center intervention study.
      SETTING: Six teaching hospitals in Nigeria. SAMPLE: Clinical records of cases of
      eclampsia treated before and 1 year after the intervention. METHODS: Doctors and
      midwives in selected hospitals were re-trained to manage eclampsia using
      magnesium sulfate according to the Pritchard protocol. MAIN OUTCOME MEASURES:
      Eclampsia case fatality rates, maternal and perinatal mortality rates before and
      after the intervention. RESULTS: A total of 219 cases of eclampsia were managed
      over a 12-month period. There were seven maternal deaths. The post intervention
      case fatality rate of 3.2% was significantly less than the pre-intervention rate
      of 15.1% (p < 0.001). The overall maternal and perinatal mortality ratios and
      rates respectively in the hospitals declined from 1199.2 to 954 per 100,000
      deliveries and 141.5 to 129.8 per 1000 births, respectively (p > 0.05).
      CONCLUSION: An intervention to build the capacity of care-providers to use an
      evidence-based protocol for the treatment of eclampsia in Nigeria was successful
      in reducing associated case fatality rate. The increased and widespread use of
      such an intervention in maternity units might contribute to the reduction of
      maternal mortality in low-income countries.

PMID- 23550633
TI  - Nitrogen and amino acids in nectar modify food selection of nectarivorous bats.
AB  - 1. Chiropterophilic flowers secrete sugar nectar with low-Nitrogen (N hereafter)
      content and small amounts of amino acids, which may function to attract animals;
      nevertheless, the role that micronutrients have on the foraging decisions of
      Neotropical nectarivorous bats is unknown. 2. We offered the nectar specialist
      Leptonycteris yerbabueanae and the omnivore Glossophaga soricina pairs of
      experimental diets mimicking either the N content or the relative abundance of 17
      amino acids found in the floral nectar from the main plant species visited by
      these bats in a tropical dry forest. We addressed the following research
      questions: (i) Do bats select N-containing or sugar-only nectar differently based
      on bats' N nutritional status? (ii) Does the presence of N in nectar affect the
      capacity of bats to discriminate and select other nectar traits such as sugar
      concentration? and (iii) Are bats able to distinguish among the flavours
      generated by the amino acid relative abundance present in the nectar from plants
      they typically encounter in nature? 3. Our results showed that: (i) bats did not
      consider nectar N content regardless of their N nutritional condition, (ii) the
      nectar specialist L. yerbabuenae showed a preference for the most concentrated
      sugar-only nectar but changed to be indifferent when nectar contained N, and
      (iii) L. yerbabuenae preferred diets without amino acids and preferred the taste
      of the amino acids present in the nectar of Pachycereus pecten (Cactaceae) over
      those present in the nectar of Ceiba aesculifolia (Bombacaceae). 4. Our results
      suggest that regardless of the low concentrations at which N and amino acids are
      present in floral nectar, their presence affects bats' food selection by
      interfering with the bats' ability to detect differences in sugar concentrations,
      and by offering particular flavours that can be perceived and selected by
      nectarivorous bats. We discuss the ecological implications of the presence of N
      and amino acids in nectar on bats' foraging decisions.

PMID- 23550634
TI  - RNA regulation of the immune system.

PMID- 23550635
TI  - The role of miRNAs in mast cells and other innate immune cells.
AB  - MicroRNAs (miRNAs) are a large class of small regulatory molecules able to
      control translation of target mRNAs and consequently to regulate various
      biological processes at a posttranscriptional level. Their importance is
      highlighted by the fact that altered miRNA expression is linked to a variety of
      human diseases, particularly cancer. Accordingly, miRNA biogenesis itself must be
      carefully regulated, both transcriptionally and posttranscriptionally. Here, we
      focus on the role of miRNAs in three lineages of myeloid cells important in both
      innate and acquired immunity: mast cells, macrophages, and dendritic cells. These
      three cell types are strategically located throughout the body tissues, where
      they can respond to foreign material, danger, and inflammatory signals. We
      discuss the role of miRNAs in these cell types, with a special focus on three of
      the most extensively studied miRNAs, namely miR-221, miR-146a, and miR-155. We
      also discuss the role of cell-to-cell transfer of miRNAs in dendritic cells, mast
      cells, and macrophages, and we speculate about possible future directions in the
      field.

PMID- 23550636
TI  - Regulation of B-cell development and function by microRNAs.
AB  - MicroRNAs (miRNAs) have emerged as a new class of gene expression regulators
      whose functions influence a myriad of biological processes, from developmental
      decisions through immune responses and numerous pathologies, including cancer and
      autoimmunity. miRNAs are small RNA molecules that drive post-transcriptional
      negative regulation of gene expression by promoting the degradation or
      translational block of their target mRNAs. Here, we review some of the data
      relating to the role of miRNAs in the regulation of the B-cell lineage, with a
      special focus on results obtained in vivo. We start by giving a general overview
      of miRNA activity, including the issue of target specificity and the experimental
      approaches more widely used to analyze the function of these molecules. We then
      go on to discuss the function of miRNAs during B-cell differentiation in the bone
      marrow and in the periphery as well as during the humoral immune response.
      Finally, we describe a few examples of the contribution of miRNAs, both as
      oncogenes and tumor suppressors, to the development of B-cell neoplasias.

PMID- 23550638
TI  - MicroRNA regulation of T-cell development.
AB  - MicroRNAs are short, 19-24 nucleotide long, RNA molecules capable of regulating
      the longevity and, to a lesser extent, translation of messenger RNA (mRNA)
      species. The function of the microRNA network, and indeed, even that of
      individual microRNA species, can have profoundly different roles in even a single
      cell type as the microRNA/mRNA composition evolves. As the role of microRNA
      within T cells has come under increasing scrutiny, several distinct checkpoints
      have been demonstrated to have a particular reliance on microRNA regulation.
      MicroRNAs are arguably most important in T cells during the earliest and last
      stages in T-cell biology. The first stages of early thymic differentiation have a
      crucial reliance on the microRNA network, while later stages and peripheral
      homeostasis are largely, although not completely, microRNA-independent. The most
      profound effects on T cells are in the activation of effector and regulatory
      functions of conventional and regulatory T cells, where microRNA deficiency
      results in a near-complete loss of function. In this review, we focus on
      integrating the research on individual microRNA into a more global understanding
      of the function of the microRNA regulatory network in T cells.

PMID- 23550637
TI  - MicroRNA function in NK-cell biology.
AB  - The important role of microRNAs in directing immune responses has become
      increasingly clear. Here, we highlight discoveries uncovering the role of
      specific microRNAs in regulating the development and function of natural killer
      (NK) cells. Furthermore, we discuss the impact of NK cells on the entire immune
      system during global and specific microRNA ablation in the settings of
      inflammation, infection, and immune dysregulation.

PMID- 23550640
TI  - Role of microRNAs and long-non-coding RNAs in CD4(+) T-cell differentiation.
AB  - CD4(+) T lymphocytes orchestrate adaptive immune responses by differentiating
      into various subsets of effector T cells such as T-helper 1 (Th1), Th2, Th17, and
      regulatory T cells. These subsets have been generally described by master
      transcription factors that dictate the expression of cytokines and receptors,
      which ultimately define lymphocyte effector functions. However, the view of T
      lymphocyte subsets as stable and terminally differentiated lineages has been
      challenged by increasing evidence of functional plasticity within CD4(+) T-cell
      subsets, which implies flexible programming of effector functions depending on
      time and space of T-cell activation. An outstanding question with broad basic and
      traslational implications relates to the mechanisms, besides transcriptional
      regulation, which define the plasticity of effector functions. In this study, we
      discuss the emerging role of regulatory non-coding RNAs in T-cell differentiation
      and plasticity. Not only microRNAs have been proven to be important for CD4(+) T
      cell differentiation, but it is also likely that the overall T-cell functioning
      is the result of a multilayered network composed by coding RNAs as well as by
      short and long non-coding RNAs. The integrated study of all the nodes of this
      network will provide a comprehensive view of the molecular mechanisms underlying
      T-cell functions in health and disease.

PMID- 23550639
TI  - MicroRNA regulation of T-cell differentiation and function.
AB  - MicroRNAs (miRNAs) are emerging as key controllers of T-cell differentiation and
      function. Their expression is dynamically regulated by extracellular signals such
      as costimulation and cytokine signals. miRNAs set thresholds for gene expression
      and optimize protein concentrations of genetic networks. Absence of individual
      miRNAs can lead to severe immune dysfunction. In this study, we review emerging
      principles and provide examples of important functions exerted by miRNAs.
      Although our understanding of miRNA function in T-cell differentiation is still
      rudimentary, the available evidence leaves no doubt that these small post
      transcriptional regulators are indispensable for proper functioning of the immune
      system.

PMID- 23550641
TI  - RNA-based mechanisms regulating host-virus interactions.
AB  - RNA interference (RNAi) is an ancient process by which non-coding RNAs regulate
      gene expression in a sequence-specific manner. The core components of RNAi are
      small regulatory RNAs, approximately 21-30 nucleotides in length, including small
      interfering RNAs (siRNAs) and microRNAs (miRNAs). The past two decades have seen
      considerable progress in our understanding of the molecular mechanisms underlying
      the biogenesis of siRNAs and miRNAs. Recent advances have also revealed the
      crucial regulatory roles played by small RNAs in such diverse processes as
      development, homeostasis, innate immunity, and oncogenesis. Accumulating evidence
      indicates that RNAi initially evolved as a host defense mechanism against viruses
      and transposons. The ability of the host small RNA biogenesis machinery to
      recognize viral double-stranded RNA replication intermediates and transposon
      transcripts is critical to this process, as is small RNA-guided targeting of RNAs
      via complementary base pairing. Collectively, these properties confer
      unparalleled specificity and precision to RNAi-mediated gene silencing as an
      effective antiviral mechanism.

PMID- 23550642
TI  - Regulation of immune responses and tolerance: the microRNA perspective.
AB  - Much has been learned about the molecular and cellular components critical for
      the control of immune responses and tolerance. It remains a challenge, however,
      to control the immune response and tolerance at the system level without causing
      significant toxicity to normal tissues. Recent studies suggest that microRNA
      (miRNA) genes, an abundant class of non-coding RNA genes that produce
      characteristic approximately 22 nucleotides small RNAs, play important roles in
      immune cells. In this article, we discuss emerging knowledge regarding the
      functions of miRNA genes in the immune system. We delve into the roles of miRNAs
      in regulating signaling strength and threshold, homeostasis, and the dynamics of
      the immune response and tolerance during normal and pathogenic immunological
      conditions. We also present observations based on analyzes of miR-181 family
      genes that indicate the potential functions of primary and/or precursor miRNAs in
      target recognition and explore the impact of these findings on target
      identification. Finally, we illustrate that despite the subtle effects of miRNAs
      on gene expression, miRNAs have the potential to influence the outcomes of normal
      and pathogenic immune responses by controlling the quantitative and dynamic
      aspects of immune responses. Tuning miRNA functions in immune cells, through gain
      and loss-of-function approaches in mice, may reveal novel approach to restore
      immune equilibrium from pathogenic conditions, such as autoimmune disease and
      leukemia, without significant toxicity.

PMID- 23550643
TI  - The Yin and Yang of microRNAs: leukemia and immunity.
AB  - Yin and Yang are two complementary forces that together describe the nature of
      real-world elements. Yin is the dark side; Yang is the light side. We describe
      microRNAs having both Yin and Yang characteristics because they can contribute to
      normal function (Yang) but also to autoimmunity, myeloproliferation, and cancer
      (Yin). We have been working on a number of microRNAs that have these dual
      characteristics and here we focus on two, miR-125b and miR-146a. We have
      concentrated on these two RNAs because we have very extensive knowledge of them,
      much of it from our laboratory, and also because they provide a strong contrast:
      the effects of overexpression of miR-125b are rapid, suggesting that it acts
      directly, whereas the effects of miR-146a are slow to develop, suggesting that
      they arise from chronic alterations in cellular behavior.

PMID- 23550644
TI  - miR-155: an ancient regulator of the immune system.
AB  - MicroRNAs (miRNAs) are a newly recognized class of regulatory genes which repress
      the expression of protein-coding genes. Numerous studies have uncovered a complex
      role for miRNAs regulating many aspects of a variety of cellular processes
      including cell growth, differentiation, and lineage commitment. In the immune
      system, miR-155 is unique in its ability to shape the transcriptome of activated
      myeloid and lymphoid cells controlling diverse biological functions ranging from
      inflammation to immunological memory. Not surprisingly, a tight control of miR
      155 expression is required to avoid malignant transformation, as evidenced by miR
      155 overexpression in many cancers of B-cell origin. In this review, we discuss
      the potential of miR-155 as a molecular target for therapeutic intervention and
      discuss the function of miR-155 in the context of protective immunity. We first
      look back into the emergence of miR-155 in evolution, which is coincidental with
      the emergence of the ancestors of the antigen receptors. We then summarize what
      we have learned about the role of miR-155 in the regulation of lymphoid subsets
      at the cellular and molecular level in the context of recent progress in this
      field.

PMID- 23550646
TI  - MicroRNAs play a central role in molecular dysfunctions linking inflammation with
      cancer.
AB  - It is now largely admitted that a pro-inflammatory environment may curtail anti
      tumor immunity and favor cancer initiation and progression. The discovery that
      small non-coding regulatory RNAs, namely microRNAs (miRNAs), regulate all aspects
      of cell proliferation, differentiation, and function has shed a new light on
      regulatory mechanisms linking inflammation and cancer. Thus, miRNAs such as miR
      21, miR-125b, miR-155, miR-196, and miR-210 that are critical for the immune
      response or hypoxia are often overexpressed in cancers and leukemias. Given the
      high number of their target transcripts, their deregulation may have a number of
      deleterious consequences, depending on the cellular context. In this review, we
      focus on how the factors encoded by transcripts targeted by these five miRNAs, be
      they transcription factors, tumor-suppressors, or regulators of different
      signaling pathways, can deregulate the immune response and favor pro-tumor
      immunity. Furthermore, we expose how the misdirected action of the main
      regulators of these miRNAs, such as nuclear factor kappaB (NF-kappaB), activator
      protein-1 (AP-1), and signal transduction and activators of transcription (STAT)
      transcription factors, or AKT and transforming growth factor beta (TGFbeta)
      signaling pathways, can contribute to decrease anti-tumor immunity and enhance
      cell proliferation and oncogenesis. We conclude by briefly discussing about how
      these discoveries may possibly lead to the development of new miRNA-based cancer
      therapies.

PMID- 23550645
TI  - mir-17-92: a polycistronic oncomir with pleiotropic functions.
AB  - Neoplastic transformation is caused by accumulation of genetic lesions that
      ultimately convert normal cells into tumor cells with uncontrolled proliferation
      and survival, unlimited replicative potential, and invasive growth. Emerging
      evidence has highlighted the functional importance of non-coding RNAs,
      particularly microRNAs (miRNAs), in the initiation and progression of tumor
      development. The mir-17-92 miRNA is among the best characterized miRNA oncogenes,
      whose genomic amplification or aberrant elevation are frequently observed in a
      variety of tumor types. Unlike protein-coding oncogenes, where one transcript
      produces one protein, mir-17-92 encodes a polycistronic miRNA transcript that
      yields six individual miRNA components. This unique gene structure, shared by
      many important miRNA oncogenes and tumor suppressors, underlies the unique
      functionality of mir-17-92 in a cell type and context-dependent manner. Recent
      functional dissection of mir-17-92 indicates that individual mir-17-92 components
      perform distinct biological functions, which collectively regulate multiple
      related cellular processes during development and disease. The structural
      complexity of mir-17-92 as a polycistronic miRNA oncogene, along with the complex
      mode of interactions among its components, constitutes the molecular basis for
      its unique functional complexity during normal and tumor development.

PMID- 23550647
TI  - A daunting task: manipulating leukocyte function with RNAi.
AB  - RNA interference (RNAi) has advanced into clinical trials. In spite of the
      progress made in systemic RNAi delivery to the liver and solid tumors, delivery
      of RNAi to leukocytes remains challenging and less advanced. Manipulating
      leukocyte function with RNAi holds great promise for streamlining the drug
      discovery process by facilitating in vivo drug target validation and for
      facilitating the development of RNAi-based therapy platforms for leukocyte
      implicated diseases, such as blood cancer, inflammation, and leukocyte-tropic
      viral infections. In this review, progress in delivery strategies of RNAi
      payloads to leukocytes, which are notoriously difficult cells to transduce with
      RNAi, is discussed with special emphasis on the challenges and potential
      opportunities for manipulating leukocyte function with RNAi.

PMID- 23550648
TI  - The emerging role of microRNAs in regulating immune and inflammatory responses in
      the lung.
AB  - Chronic inflammatory diseases of the lung are leading causes of morbidity and
      mortality worldwide. Many of these disorders can be attributed to abnormal immune
      responses to environmental stimuli and infections. As such, understanding the
      innate host defense pathways and their regulatory systems will be critical to
      developing new approaches to treatment. In this regard, there is increasing
      interest in the role of microRNAs (miRNAs) in the regulation of pulmonary innate
      host defense responses and the inflammatory sequelae in respiratory disease. In
      this review, we discuss recent findings that indicate an important role for
      miRNAs in the regulation in mouse models of various respiratory diseases and in
      host defense against bacterial and viral infection. We also discuss the potential
      utility and limitations of targeting these molecules as anti-inflammatory
      strategies and also as a means to improve pathogen clearance from the lung.

PMID- 23550650
TI  - Live or let die: posttranscriptional gene regulation in cell stress and cell
      death.
AB  - Studies of the regulation of gene expression historically focused on
      transcription. However, during stress and apoptosis, profound gene expression
      changes occur more rapidly and globally than is possible by regulating
      transcription. Posttranscriptional changes in mRNA processing and translation in
      response to diverse stresses shut down most protein translation to conserve
      energy and lead to rapid remodeling of the proteome to promote repair. Pre-mRNA
      splicing and mRNA stability are fundamentally altered under some stress
      conditions. Stress pathways coordinate a cytoprotective repair response, while
      simultaneously initiating signaling that can ultimately trigger cell death. How
      the cell mediates the decision between repair and apoptosis is largely not
      understood. In some stresses, microRNAs may tip the balance. Here, we review what
      is known about posttranscriptional gene regulation during stress, focusing on
      what is still unknown and how new technologies might be used to understand what
      changes are most physiologically important in different forms of stress and
      death.

PMID- 23550651
TI  - Post-transcriptional regulatory networks in immunity.
AB  - Post-transcriptional mechanisms that modulate global and/or transcript-specific
      mRNA stability and translation contribute to the rapid and flexible control of
      gene expression in immune effector cells. These mechanisms rely on RNA-binding
      proteins (RBPs) that direct regulatory complexes (e.g. exosomes, deadenylases,
      decapping complexes, RNA-induced silencing complexes) to the 3'-untranslated
      regions of specific immune transcripts. Here, we review the surprising variety of
      post-transcriptional control mechanisms that contribute to gene expression in the
      immune system and discuss how defects in these pathways can contribute to
      autoimmune disease.

PMID- 23550649
TI  - Control of alternative splicing in immune responses: many regulators, many
      predictions, much still to learn.
AB  - Most mammalian pre-mRNAs are alternatively spliced in a manner that alters the
      resulting open reading frame. Consequently, alternative pre-mRNA splicing
      provides an important RNA-based layer of protein regulation and cellular
      function. The ubiquitous nature of alternative splicing coupled with the advent
      of technologies that allow global interrogation of the transcriptome have led to
      an increasing awareness of the possibility that widespread changes in splicing
      patterns contribute to lymphocyte function during an immune response. Indeed, a
      few notable examples of alternative splicing have clearly been demonstrated to
      regulate T-cell responses to antigen. Moreover, several proteins key to the
      regulation of splicing in T cells have recently been identified. However, much
      remains to be done to truly identify the spectrum of genes that are regulated at
      the level of splicing in immune cells and to determine how many of these are
      controlled by currently known factors and pathways versus unknown mechanisms.
      Here, we describe the proteins, pathways, and mechanisms that have been shown to
      regulate alternative splicing in human T cells and discuss what is and is not
      known about the genes regulated by such factors. Finally, we highlight unifying
      themes with regards to the mechanisms and consequences of alternative splicing in
      the adaptive immune system and give our view of important directions for future
      studies.

PMID- 23550652
TI  - Molecular control of Tfh-cell differentiation by Roquin family proteins.
AB  - Post-transcriptional gene regulation by RNA-binding proteins is a fast and
      effective way to adapt gene expression and change cellular responses. These trans
      acting factors have been involved in a number of cell fate decisions, and their
      mutation is often associated with the development of disease. The RNA-binding
      protein Roquin-1 has been found to be crucial in the maintenance of peripheral
      tolerance and the prevention of autoimmune disease. This review describes the
      molecular role of Roquin family proteins in the control of follicular T-helper
      cell differentiation. Here, we discuss the redundant regulation of Icos and Ox40
      costimulatory receptor mRNAs by Roquin-1 and Roquin-2 proteins. A major focus is
      placed on the distinct activity of Roquin-1 or Roquin-2 proteins in the mouse
      models of conditional gene targeting. These recent data are then integrated into
      an interpretation of altered Roquin protein function in the sanroque mouse that
      expresses the Roquin-1 protein with just one amino acid substitution and,
      different from the Roquin-1-deficient mouse, develops lupus-like autoimmune
      disease.

PMID- 23550655
TI  - Mass action expressions for bidentate adsorption in surface complexation
      modeling: theory and practice.
AB  - The inclusion of multidentate adsorption reactions has improved the ability of
      surface complexation models (SCM) to predict adsorption to mineral surfaces, but
      variation in the mass action expression for these reactions has caused persistent
      ambiguity and occasional mishandling. The principal differences are the exponent
      (alpha) for the activity of available surface sites and the inclusion of surface
      site activity on a molar concentration versus fraction basis. Exemplified by
      bidentate surface complexation, setting alpha at two within the molar-based
      framework will cause critical errors in developing a self-consistent model.
      Despite the publication of several theoretical discussions regarding appropriate
      approaches, mishandling and confusion has persisted in the model applications
      involving multidentate surface complexes. This review synthesizes the theory of
      modeling multidentate surface complexes in a style designed to enable
      improvements in SCM practice. The implications of selecting an approach for
      multidentate SCM are illustrated with a previously published data set on U(VI)
      adsorption to goethite. To improve the translation of theory into improved
      practice, the review concludes with suggestions for handling multidentate
      reactions and publishing results that can avoid ambiguity or confusion. Although
      most discussion is exemplified by the generic bidentate case, the general issues
      discussed are relevant to higher denticity adsorption.

PMID- 23550656
TI  - Molecular dynamics simulations of CO2 formation in interstellar ices.
AB  - CO2 ice is one of the most abundant components in ice-coated interstellar ices
      besides H2O and CO, but the most favorable path to CO2 ice is still unclear.
      Molecular dynamics calculations on the ultraviolet photodissociation of different
      kinds of CO-H2O ice systems have been performed at 10 K in order to demonstrate
      that the reaction between CO and an OH molecule resulting from H2O
      photodissociation through the first excited state is a possible route to form CO2
      ice. However, our calculations, which take into account different ice surface
      models, suggest that there is another product with a higher formation probability
      ((3.00 +/- 0.07) * 10(-2)), which is the HOCO complex, whereas the formation of
      CO2 has a probability of only (3.6 +/- 0.7) * 10(-4). The initial location of the
      CO is key to obtain reaction and form CO2: the CO needs to be located deep into
      the ice. The HOCO complex becomes trapped in the cold ice surface in the trans
      HOCO minimum because it quickly loses its internal energy to the surrounding ice,
      preventing further reaction to H + CO2. Several laboratory experiments have been
      carried out recently, and they confirm that CO2 can also be formed through other,
      different routes. Here we compare our theoretical results with the data available
      from experiments studying the formation of CO2 through a similar pathway as ours,
      even though the initial conditions were not exactly the same. Our results also
      show that the HCO van der Waals complex can be formed through the interaction of
      CO with the H atom that is formed as a product of H2O photodissociation. Thus,
      the reaction of the H atom photofragment following H2O photodissociation with CO
      can be a possible route to form HCO ice. 

PMID- 23550654
TI  - Regulation of miRNA biogenesis and turnover in the immune system.
AB  - MicroRNAs (miRNAs) have emerged as important regulators of gene expression in
      diverse biological processes ranging from cell proliferation and survival to
      organ development and immunity. Here, we review mechanisms that regulate the
      expression of miRNAs themselves in the immune system. Like protein-coding genes,
      miRNAs can be regulated at the transcriptional level, downstream of signaling
      pathways and circuits that activate or inhibit transcription factors and
      chromatin remodeling. The resulting primary miRNAs are processed into active
      mature miRNAs through a series of biochemical steps, and miRNA abundance can be
      regulated at each step of this biogenesis pathway. Recent work has uncovered
      regulation of mature miRNA turnover in the immune system as well. A better
      understanding of these processes and their regulation by immunogenic stimuli is
      critical for integrating miRNAs into current models of gene expression networks
      that determine cell identity and immune function.

PMID- 23550657
TI  - High-throughput simultaneous genotyping of human platelet antigen-1 to -16 by
      using suspension array.
AB  - BACKGROUND: Comprehensive and accurate detection of human platelet antigens
      (HPAs) plays a significant role in diagnosis and prevention of the platelet (PLT)
      alloimmune syndromes and ensuring clinical safety of patients undergoing PLT
      transfusion. The majority of the available methods are incapable of performing
      high-throughput simultaneous detection of HPA-1 to -16, and the accuracy of many
      methods needs to be further enhanced. STUDY DESIGN AND METHODS: We have developed
      a new HPA-genotyping method for simultaneous detection of HPA-1 to -16 based on
      suspension array technology. A total of 216 samples from Chinese Han donors in
      Xi'an were genotyped using the developed method, and all the samples again were
      genotyped using polymerase chain reaction (PCR) sequence-based typing (PCR-SBT),
      which is considered the gold standard. RESULTS: All 216 samples were successfully
      genotyped for HPA-1 to -16 using both our method and PCR-SBT. Results showed that
      the genotype and allele frequencies obtained using our method were fully
      consistent with those obtained using PCR-SBT. CONCLUSION: Our method provides
      accurate, high-throughput, and simultaneous genotyping of HPA-1 to -16 and will
      serve as the foundation for large-scale clinical genotyping of HPAs and for the
      establishment of an HPA-typed PLT donor registry.

PMID- 23550653
TI  - Exploring the RNA world in hematopoietic cells through the lens of RNA-binding
      proteins.
AB  - The discovery of microRNAs has renewed interest in posttranscriptional modes of
      regulation, fueling an emerging view of a rich RNA world within our cells that
      deserves further exploration. Much work has gone into elucidating genetic
      regulatory networks that orchestrate gene expression programs and direct cell
      fate decisions in the hematopoietic system. However, the focus has been to
      elucidate signaling pathways and transcriptional programs. To bring us one step
      closer to reverse engineering the molecular logic of cellular differentiation, it
      will be necessary to map posttranscriptional circuits as well and integrate them
      in the context of existing network models. In this regard, RNA-binding proteins
      (RBPs) may rival transcription factors as important regulators of cell fates and
      represent a tractable opportunity to connect the RNA world to the proteome. ChIP
      seq has greatly facilitated genome-wide localization of DNA-binding proteins,
      helping us to understand genomic regulation at a systems level. Similarly,
      technological advances such as CLIP-seq allow transcriptome-wide mapping of RBP
      binding sites, aiding us to unravel posttranscriptional networks. Here, we review
      RBP-mediated posttranscriptional regulation, paying special attention to findings
      relevant to the immune system. As a prime example, we highlight the RBP Lin28B,
      which acts as a heterochronic switch between fetal and adult lymphopoiesis.

PMID- 23550658
TI  - Markers of systemic inflammation in psoriasis: a systematic review and meta
      analysis.
AB  - Studies investigating systemic inflammation in psoriasis use different serum
      markers and report discrepant results. We set out to determine whether systemic
      inflammation is elevated in patients with psoriasis compared with healthy
      controls, and to measure the extent of this elevation, by summarizing available
      data on serum inflammatory markers. PubMed, Embase and Web of Science were
      searched from inception to March 2011. We included studies comparing the serum
      inflammatory markers interleukin (IL)-1beta, IL-6, IL-10, C-reactive protein
      (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin and tumour necrosis
      factor (TNF)-alpha in patients with psoriasis and healthy controls. Differences
      in serum marker levels between patients and controls were pooled as standardized
      mean differences (SMDs; Cohen's d) using a random-effects model. Seventy-eight
      studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque)
      psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy
      controls for IL-6 [d = 1.32, 95% confidence interval (CI) 0.83-1.81], CRP (d =
      1.83, 95% CI 0.76-2.90), TNF-alpha (d = 1.32, 95% CI 0.86-1.79), E-selectin (d =
      1.78, 95% CI 1.32-2.25) and ICAM-1 (d = 1.77, 95% CI 1.15-2.39). The SMD between
      cases and controls for IL-1beta and IL-10 was not significant. Age had a
      significant effect on the SMD for IL-6 and TNF-alpha. For IL-6 the effect size
      was higher for plaque psoriasis studies (d = 1.98). The effect size was not
      influenced by the Psoriasis Area and Severity Index, measurement method or
      quality assessment. The pooled analyses suggest modest but significantly elevated
      levels of the proinflammatory cytokines in the serum of patients with psoriasis
      with predominantly severe disease. To what extent this modest increment is
      clinically relevant could be investigated in a synthesis of all studies measuring
      inflammation before and after antipsoriatic therapy.

PMID- 23550659
TI  - Onychodermis (specialized nail mesenchyme) is present in ectopic nails.

PMID- 23550660
TI  - Meta-analysis: the risk of venous thromboembolism in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD)
      and ulcerative colitis (UC), is a systemic disorder that predominantly affects
      the bowels but is also associated with venous thromboembolism (VTE). AIM: To
      provide a quantitative assessment of the association of IBD with venous
      thromboembolism risk and to explore the possible sources of heterogeneity in the
      current literature, a meta-analysis of case-control and cohort studies was
      conducted. METHODS: Studies were identified by a literature search of the PubMed
      and Scopus databases (from inception inclusive 31 December 2012) for English
      language studies. Summary relative risks (RRs) with 95% confidence intervals
      (CIs) were calculated with fixed- and random-effects models. Several subgroup
      analyses were performed to explore potential study heterogeneity and bias.
      RESULTS: Eleven studies met our inclusion criteria. The summary RR for deep
      venous thromboembolism (DVT) and pulmonary embolism (PE) comparing subjects both
      with and without IBD was 2.20 (95% CI 1.83-2.65). After adjusting for obesity and
      smoking, summary relative risks near 2.0 were seen for venous thromboembolism in
      both UC and CD patients. CONCLUSION: This meta-analysis showed that inflammatory
      bowel disease is associated with an approximately two-fold increase in the risk
      of venous thromboembolism.

PMID- 23550661
TI  - Silent, invisible and unacknowledged: experiences of young caregivers of single
      parents diagnosed with multiple sclerosis.
AB  - THE STUDY'S RATIONALE: Most people diagnosed with multiple sclerosis (MS) choose
      to live at home without known consequences for their children. AIMS AND
      OBJECTIVES: To study the personal experience of being a young caregiver of a
      chronically ill parent diagnosed with MS. METHODOLOGICAL DESIGN AND
      JUSTIFICATION: Phenomenology was the methodological approach of the study since
      it gives an inside information of the lived experience. ETHICAL ISSUES AND
      APPROVAL: The study was approved by the National Bioethics Committee and reported
      to the Data Protection Authority. RESEARCH METHODS: We explored in 21 interviews
      the lived experience of 11 young caregivers who had cared for single chronically
      ill parents, diagnosed with MS. RESULTS: The participants felt silent, invisible
      and unacknowledged as caregivers and received limited professional assistance.
      They were left to provide their parents with intimate physical and emotional care
      and support that was demanding, embarrassing and quite difficult while feeling
      unsupported, excluded and abandoned. Their caring responsibilities lead to severe
      restrictions in life as their parents' disease progressed and they lived without
      a true childhood; left to manage far too many responsibilities completely on
      their own and at a young age. At the time of the interviews, most of the
      participants had left their post as primary caregivers. They were learning to let
      go of the emotional pain, some of them with a welcomed partner. Most of them were
      experiencing a healthy transition and personal growth, existentially moving from
      feeling abandoned towards feeling independent. However, some of them were still
      hurting. STUDY LIMITATIONS: In choosing participants for the study a sampling
      bias may have occurred. CONCLUSIONS: Health professionals are urged to provide
      information, support and guidance for young carers in a culturally sensitive way
      and to take on the leading role of helping and empowering children and
      adolescents in similar situations.

PMID- 23550663
TI  - A meta-analysis of experimental warming effects on terrestrial nitrogen pools and
      dynamics.
AB  - Global warming may have profound effects on terrestrial ecosystems. However, a
      comprehensive evaluation of the effects of warming on ecosystem nitrogen (N)
      pools and dynamics is not available. Here, we compiled data of 528 observations
      from 51 papers and carried out a meta-analysis of experimental warming effects on
      13 variables related to terrestrial N pools and dynamics. We found that, on
      average, net N mineralization and net nitrification rate were increased by 52.2
      and 32.2%, respectively, under experimental warming treatment. N pools were also
      increased by warming, although the magnitude of this increase was less than that
      of N fluxes. Soil microbial N and N immobilization were not changed by warming,
      probably because microbes are limited by carbon sources. Grassland and
      shrubland/heathland were less responsive to warming than forest, probably because
      the reduction of soil moisture by warming offset the temperature effect in these
      areas. Soil heating cable and all-day treatment appeared to be the most effective
      method on N cycling among all treatment methods. Results of this meta-analysis
      are useful for better understanding the response of N cycling to global warming
      and the underlying mechanism of warming effects on plants and ecosystem
      functions.

PMID- 23550662
TI  - Effects of negative pressure wound therapy on healing of free full-thickness skin
      grafts in dogs.
AB  - OBJECTIVE: To compare healing of free, full-thickness, meshed skin grafts under
      negative pressure wound therapy (NPWT) with bolster dressings in dogs. STUDY
      DESIGN: Randomized, controlled experimental study, paired design. ANIMALS: Dogs
      (n = 5) METHODS: Full-thickness skin wounds (4 cm * 1.5 cm) were created
      bilaterally on the antebrachia of 5 dogs (n = 10). Excised skin was grafted to
      the contralateral limb. Grafts were randomized to NPWT or bolster dressings
      (control; CON). NPWT was applied continuously for 7 days. Grafts were evaluated
      on Days 2, 4, 7, 10, 14, and 17, biopsied on days 0, 4, 7, and 14, and had
      microbial culture on Day 7. Outcome variables were: time to first appearance of
      granulation tissue, percent graft necrosis, and percent open mesh. Significance
      was set at P < .05. Histologic findings, culture results, and graft appearance
      were reported. RESULTS: Granulation tissue appeared earlier in the NPWT grafts
      compared with CON grafts. Percent graft necrosis and remaining open mesh area
      were both greater in CON grafts compared with NPWT grafts at most time points.
      Histologic results showed no significant difference in all variables measured,
      and all cultures were negative. CONCLUSIONS: Variables of graft acceptance were
      superior when NPWT was used in the first week post-grafting. Fibroplasia was
      enhanced, open meshes closed more rapidly and less graft necrosis occurred with
      NPWT application. More preclinical studies are required to evaluate histologic
      differences.

PMID- 23550664
TI  - The effects of differential extraction conditions on the premature lysis of
      spermatozoa.
AB  - The purpose of this study was to determine the effect Proteinase K, sodium
      dodecyl sulfate (SDS), incubation times, and temperatures had on differential
      extraction efficiencies and the premature lysis of spermatozoa. The effect was
      measured using Quantifiler(r) Duo and IdentifilerTM PCR Amplification kits, where
      the resultant male and female DNA concentrations and their ratios within the
      nonsperm- and sperm fractions (SFs) were determined. Comparisons between expected
      and observed ratios illustrate the quantity of female DNA in the SF increased
      when Proteinase K was absent during the initial incubation. Additionally, there
      is no indication of simultaneous sperm and epithelial cell lysis in the absence
      of DTT at Proteinase K concentrations ranging from 10 to 300 MUg/mL. All other
      conditions exhibited minimal variation in DNA concentration. Therefore, despite
      the various protocols used for the differential lysis of cell mixtures
      encountered in casework, the method is robust and successful at most conditions.

PMID- 23550666
TI  - Something new under the sun? The Mediterranean diet and cardiovascular health.

PMID- 23550665
TI  - Effects of cognitive stimulation therapy Japanese version (CST-J) for people with
      dementia: a single-blind, controlled clinical trial.
AB  - OBJECTIVES: Cognitive stimulation therapy (CST) has shown to have significant
      benefits in improving the cognitive function and quality of life (QOL) in people
      with mild-to-moderate dementia in a UK randomized controlled trial (RCT). We
      developed and examined the Japanese version of group CST (CST-J) in a single
      blind, controlled clinical trial. METHOD: CST-J consisting of 14 sessions was
      administered to a treatment group (n = 26) twice a week for 7 weeks. The
      treatment group was compared with a control group (n = 30). Based on single
      blindness, cognition was evaluated by a researcher, and QOL and mood were rated
      by the participants themselves. Additionally, QOL and mood of participants were
      rated by care workers who were not blind but who observed them most directly in
      their daily life (important for social validity). RESULTS: A linear mixed model
      was used for analyses of cognition and QOL. There were significant improvements
      in cognition [COGNISTAT (Neurobehavioral Cognitive Status Examination) and MMSE
      (Mini-Mental State Examination)] for the treatment group compared with the
      control group (p < 0.01). Regarding QOL, the EQ-5D was significant (p = 0.019)
      and the QoL-AD (Quality of Life - Alzheimer's Disease) showed a positive trend (p
      = 0.06) when rated by care workers, although not when rated by the participants
      themselves. Using a nonparametrical analysis, there were significant improvements
      in the face scale for mood when rated by both the participants (p < 0.01) and the
      care workers (p = 0.017). CONCLUSION: The CST-J shows promising improvements in
      cognition, mood, and aspects of QOL for people with dementia in Japanese care
      settings. A large RCT is now needed.

PMID- 23550667
TI  - Lessons from Vermont's health care reform.

PMID- 23550668
TI  - Combination antifungal therapy for cryptococcal meningitis.
AB  - BACKGROUND: Combination antifungal therapy (amphotericin B deoxycholate and
      flucytosine) is the recommended treatment for cryptococcal meningitis but has not
      been shown to reduce mortality, as compared with amphotericin B alone. We
      performed a randomized, controlled trial to determine whether combining
      flucytosine or high-dose fluconazole with high-dose amphotericin B improved
      survival at 14 and 70 days. METHODS: We conducted a randomized, three-group, open
      label trial of induction therapy for cryptococcal meningitis in patients with
      human immunodeficiency virus infection. All patients received amphotericin B at a
      dose of 1 mg per kilogram of body weight per day; patients in group 1 were
      treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2
      concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2
      weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg
      twice daily for 2 weeks. RESULTS: A total of 299 patients were enrolled. Fewer
      deaths occurred by days 14 and 70 among patients receiving amphotericin B and
      flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by
      day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08;
      unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI,
      0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no
      significant effect on survival, as compared with monotherapy (hazard ratio for
      death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by
      70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was
      associated with significantly increased rates of yeast clearance from
      cerebrospinal fluid (-0.42 log10 colony-forming units [CFU] per milliliter per
      day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3,
      respectively; P<0.001 for both comparisons). Rates of adverse events were similar
      in all groups, although neutropenia was more frequent in patients receiving a
      combination therapy. CONCLUSIONS: Amphotericin B plus flucytosine, as compared
      with amphotericin B alone, is associated with improved survival among patients
      with cryptococcal meningitis. A survival benefit of amphotericin B plus
      fluconazole was not found. (Funded by the Wellcome Trust and the British
      Infection Society; Controlled-Trials.com number, ISRCTN95123928.).

PMID- 23550670
TI  - Monetary costs of dementia in the United States.
AB  - BACKGROUND: Dementia affects a large and growing number of older adults in the
      United States. The monetary costs attributable to dementia are likely to be
      similarly large and to continue to increase. METHODS: In a subsample (856
      persons) of the population in the Health and Retirement Study (HRS), a nationally
      representative longitudinal study of older adults, the diagnosis of dementia was
      determined with the use of a detailed in-home cognitive assessment that was 3 to
      4 hours in duration and a review by an expert panel. We then imputed cognitive
      status to the full HRS sample (10,903 persons, 31,936 person-years) on the basis
      of measures of cognitive and functional status available for all HRS respondents,
      thereby identifying persons in the larger sample with a high probability of
      dementia. The market costs associated with care for persons with dementia were
      determined on the basis of self-reported out-of-pocket spending and the
      utilization of nursing home care; Medicare claims data were used to identify
      costs paid by Medicare. Hours of informal (unpaid) care were valued either as the
      cost of equivalent formal (paid) care or as the estimated wages forgone by
      informal caregivers. RESULTS: The estimated prevalence of dementia among persons
      older than 70 years of age in the United States in 2010 was 14.7%. The yearly
      monetary cost per person that was attributable to dementia was either $56,290
      (95% confidence interval [CI], $42,746 to $69,834) or $41,689 (95% CI, $31,017 to
      $52,362), depending on the method used to value informal care. These individual
      costs suggest that the total monetary cost of dementia in 2010 was between $157
      billion and $215 billion. Medicare paid approximately $11 billion of this cost.
      CONCLUSIONS: Dementia represents a substantial financial burden on society, one
      that is similar to the financial burden of heart disease and cancer. (Funded by
      the National Institute on Aging.).

PMID- 23550669
TI  - Intermittent versus continuous androgen deprivation in prostate cancer.
AB  - BACKGROUND: Castration resistance occurs in most patients with metastatic hormone
      sensitive prostate cancer who are receiving androgen-deprivation therapy.
      Replacing androgens before progression of the disease is hypothesized to prolong
      androgen dependence. METHODS: Men with newly diagnosed, metastatic, hormone
      sensitive prostate cancer, a performance status of 0 to 2, and a prostate
      specific antigen (PSA) level of 5 ng per milliliter or higher received a
      luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7
      months. We then randomly assigned patients in whom the PSA level fell to 4 ng per
      milliliter or lower to continuous or intermittent androgen deprivation, with
      patients stratified according to prior or no prior hormonal therapy, performance
      status, and extent of disease (minimal or extensive). The coprimary objectives
      were to assess whether intermittent therapy was noninferior to continuous therapy
      with respect to survival, with a one-sided test with an upper boundary of the
      hazard ratio of 1.20, and whether quality of life differed between the groups 3
      months after randomization. RESULTS: A total of 3040 patients were enrolled, of
      whom 1535 were included in the analysis: 765 randomly assigned to continuous
      androgen deprivation and 770 assigned to intermittent androgen deprivation. The
      median follow-up period was 9.8 years. Median survival was 5.8 years in the
      continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard
      ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to
      1.23). Intermittent therapy was associated with better erectile function and
      mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter.
      There were no significant differences between the groups in the number of
      treatment-related high-grade adverse events. CONCLUSIONS: Our findings were
      statistically inconclusive. In patients with metastatic hormone-sensitive
      prostate cancer, the confidence interval for survival exceeded the upper boundary
      for noninferiority, suggesting that we cannot rule out a 20% greater risk of
      death with intermittent therapy than with continuous therapy, but too few events
      occurred to rule out significant inferiority of intermittent therapy.
      Intermittent therapy resulted in small improvements in quality of life. (Funded
      by the National Cancer Institute and others; ClinicalTrials.gov number,
      NCT00002651.).

PMID- 23550671
TI  - Globalization, climate change, and human health.

PMID- 23550672
TI  - Images in clinical medicine. Primary Raynaud's phenomenon.

PMID- 23550673
TI  - Clinical problem-solving. The essential element.

PMID- 23550674
TI  - Did the PREDIMED trial test a Mediterranean diet?

PMID- 23550675
TI  - Efficiently killing a sugar-coated yeast.

PMID- 23550676
TI  - New cells in old hearts.

PMID- 23550677
TI  - Transfusion for acute upper gastrointestinal bleeding.

PMID- 23550678
TI  - Transfusion for acute upper gastrointestinal bleeding.

PMID- 23550679
TI  - Transfusion for acute upper gastrointestinal bleeding.

PMID- 23550680
TI  - Transfusion for acute upper gastrointestinal bleeding.

PMID- 23550681
TI  - Global health.

PMID- 23550682
TI  - Global health.

PMID- 23550683
TI  - Global health.

PMID- 23550684
TI  - Antibody depletion by bortezomib through blocking of antigen presentation.

PMID- 23550685
TI  - Hepatotoxicity with combination of vemurafenib and ipilimumab.

PMID- 23550686
TI  - Images in clinical medicine. Stellate cataract.

PMID- 23550687
TI  - Diffusion-weighted imaging changes in cerebral watershed distribution following
      neonatal encephalopathy are not invariably associated with an adverse outcome.
AB  - AIM: Patterns of injury in term-born infants with neonatal encephalopathy
      following hypoxia-ischaemia are seen earlier and are more conspicuous on
      diffusion-weighted magnetic resonance imaging (DW-MRI) than on conventional
      imaging. Although the prognostic value of DW-MRI in infants with basal ganglia
      and thalamic damage has been established, data in infants in whom there is
      extensive injury in a watershed distribution are limited. The aim of this study
      was to assess cognitive and functional motor outcome in a cohort of infants with
      changes in a predominantly watershed distribution injury on neonatal cerebral
      MRI, including DWI. METHOD: DW-MRI findings in infants with neonatal
      encephalopathy following hypoxia-ischaemia were evaluated retrospectively. Twenty
      two infants in whom DWI changes exhibited a predominantly watershed distribution
      were enrolled in the study (10 males, 12 females; mean birthweight 3337 g, 2830
      3900 g; mean gestational age 40.5 wks, 37.9-42.1 wks). Follow-up MRI data at the
      age of 3 months (n=15) and over the age of 18 months (n=7) were analysed. In
      survivors, neurodevelopmental outcome was assessed with the Griffiths Mental
      Development Scales at the age of at least 18 months. Amplitude-integrated
      electroencephalography was used to score background patterns and the occurrence
      of epileptiform activity. RESULTS: DW-MRI revealed abnormalities that were
      bilateral in all infants and symmetrical in 10. The posterior regions were more
      severely affected in five infants and the anterior regions in three. Watershed
      injury occurred in isolation in 10 out of 22 infants and was associated with
      involvement of the basal ganglia and thalami in the other 12, of whom seven died.
      Cystic evolution, seen on MRI at age 3 months, occurred in three of the 15
      surviving infants. Neurodevelopmental assessment of the surviving infants was
      performed at a median age of 35 months (range 18-48 mo). Of the five survivors
      with basal ganglia and thalamic involvement, two developed cerebral palsy, one
      had a developmental quotient of less than 85, and two had a normal outcome. Of
      the 10 infants with isolated watershed injury, nine had an early normal motor and
      cognitive outcome. In all infants with a favourable outcome, background recovery
      was seen on amplitude integrated EEG within 48 hours after birth. CONCLUSION:
      Extensive DWI changes in a watershed distribution in term-born neonates are not
      invariably associated with adverse sequelae, even in the presence of cystic
      evolution. Associated lesions of the basal ganglia and thalami are a better
      predictor of adverse sequelae than the extent and severity of the watershed
      abnormalities seen on DW-MRI.

PMID- 23550688
TI  - Cast application of four weeks' duration significantly affects hair length,
      diameter and density.
AB  - BACKGROUND: Localized hypertrichosis following cast application has been
      recorded, yet no studies characterized these changes systematically. OBJECTIVE:
      To evaluate changes of hair length, diameter and density on the legs in patients
      after cast application. MATERIALS AND METHODS: Patients with leg injuries and
      cast application of at least 4 weeks' duration were included in the study.
      Immediately after cast removal, hair sampling was taken from both legs; cast and
      control sides. Hair length and diameter were measured by Olympus microscope
      software. Patients were also analyzed for global changes by three blinded
      dermatologists. RESULTS: Fourteen patients, seven of whom were male, were
      included in this study. On the cast side, both hair length and diameter were
      significantly greater than the control side (p < 0.001). Subjective evaluations
      by three blinded dermatologists agreed well with objective measurements and also
      demonstrated an increase in overall density. Degrees of hair changes did not
      correlate with the distance from injury sites. CONCLUSION: Cast application of at
      least 4 weeks' duration significantly stimulates hair growth in a diffuse
      pattern. This could possibly lead to novel therapeutic approaches for different
      types of alopecias.

PMID- 23550689
TI  - Quantitative temperature-depending mapping of mechanical properties of bitumen at
      the nanoscale using the AFM operated with PeakForce TappingTM mode.
AB  - The mechanical properties of bitumen, such as elasticity/Young's modulus,
      stickiness/adhesion, hardness and energy loss, and sample deformation were
      acquired quantitatively and simultaneously with the topology at the microscale,
      discriminating clearly two separate phases within the bitumen. Temperature
      dependent measurements revealed detailed and specific data about the changes of
      these properties with temperature, enabling the development of predictive models
      for the performance and durability of asphalt.

PMID- 23550691
TI  - Ultrasound-mediated strategies in opening brain barriers for drug brain delivery.
AB  - INTRODUCTION: Though many agents have therapeutic potentials for brain diseases,
      few have been used in clinical environments because of the brain barriers. As an
      effective interventional technique, ultrasound (US) could be a potentially
      feasible approach to disrupt the blood-brain barrier (BBB) and deliver
      therapeutic agents into the brain. AREAS COVERED: This article reviews up-to-date
      ultrasound-mediated strategies in opening the brain barriers for drug brain
      delivery. The mechanisms and problems of these approaches are discussed, as well
      as the challenges and potentials associated with the ultrasound-mediated
      strategies that are currently available or under development. EXPERT OPINION:
      Despite recent successes in opening the blood brain barrier (BBB) via microbubble
      enhanced focused ultrasound, the exact mechanisms of how the barrier is
      disrupted, remains unknown. A complete understanding of the mechanisms involved
      in the ultrasound-mediated disruption of the BBB and improving the efficiency of
      drug delivery to targeted brain regions can greatly facilitate the successful
      development and translation of the technology.

PMID- 23550692
TI  - Stability assessment of gas mixtures containing monoterpenes in varying cylinder
      materials and treatments.
AB  - Studies of climate change increasingly recognize the diverse influences exerted
      by monoterpenes in the atmosphere, including roles in particulates, ozone
      formation, and oxidizing potential. Measurements of key monoterpenes suggest
      atmospheric mole fractions ranging from low pmol/mol (parts-per-trillion; ppt) to
      nmol/mol (parts-per-billion; ppb), depending on location and compound. To
      accurately establish the mole fraction trends, assess the role of monoterpenes in
      atmospheric chemistry, and relate measurement records from many laboratories and
      researchers, it is essential to have good calibration standards. The feasibility
      of preparing well-characterized, stable gas cylinder standards for monoterpenes
      at the nmol/mol level was previously tested using treated (Aculife IV) aluminum
      gas cylinders at NIST. Results for 4 of the 11 monoterpenes, monitored versus an
      internal standard of benzene, indicated stability in these treated aluminum gas
      cylinders for over 6 months and projected long-term (years) stability. However,
      the mole fraction of the key monoterpene beta-pinene decreased, while the mole
      fractions of alpha-pinene, d-limonene (R-(+)-limonene), p-cymene, and camphene (a
      terpene not present in the initial gas mixture) increased, indicating a chemical
      transformation of beta-pinene to these species. A similar pattern of decreasing
      mole fraction was observed in alpha-pinene where growth of d-limonene, p-cymene,
      and camphene has been observed in treated gas cylinders prepared with a mixture
      of just alpha-pinene and benzene as the internal standard. The current research
      discusses the testing of other cylinders and treatments for the potential of long
      term stability of monoterpenes in a gas mixture. In this current study, a similar
      pattern of decreasing mole fraction, although somewhat improved short-term
      stability, was observed for beta-pinene and alpha-pinene, with growth of d
      limonene, p-cymene, and camphene, in nickel-plated carbon steel cylinders. beta
      Pinene and alpha-pinene showed excellent stability at over 6 months in aluminum
      cylinders treated with a different process (Experis) than used in the original
      study. 

PMID- 23550693
TI  - Decreased peripheral blood CD4+/CD25+ regulatory T cells in patients with
      alcoholic hepatitis.
AB  - BACKGROUND: Development of alcoholic hepatitis (AH) may be favored by the
      activation of the innate immune response. Recently, decreased numbers of
      circulating regulatory T cells (Tregs) have been reported in diseases associated
      with an immune activation status, but no studies have focused so far, in
      investigating the distribution of Tregs in chronic alcoholism and its potential
      association with liver disease. Here, we analyzed for the first time the
      frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its
      relationship with the production of inflammatory cytokines by PB monocytes and
      dendritic cells (DCs). METHODS: PB samples from 25 male patients with AH were
      studied; in parallel, 15 male chronic alcoholic patients without liver disease
      (AWLD) and 17 male healthy donors were also studied, as controls. The
      distribution of CD4+CD25hiCD127-/lo Tregs and their maturation subsets (naive,
      central memory, and peripheral memory Tregs) was analyzed by flow cytometry.
      Spontaneous and in vitro-stimulated production of inflammatory cytokines by PB
      monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.
      RESULTS: Patients with AH showed decreased (p < 0.05) numbers of PB
      CD4+CD25hiCD127-/lo Tregs at the expense of all maturation-associated subsets,
      while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB
      CD4+CD25hiCD127-/lo Tregs. Interestingly, significantly increased amounts of
      spontaneously produced inflammatory cytokines were found among circulating
      monocyte-derived DCs and monocytes from AH (and AWLD) patients in comparison with
      healthy donors. Conversely, the ability of these cell subsets to produce
      cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2
      control groups. CONCLUSIONS: PB CD4+CD25hiCD127-/lo Tregs are significantly
      decreased in patients with AH when compared to both healthy and AWLD; this may
      contribute to explain the more pronounced activation of the innate immune
      response observed in AH, as reflected by an increased secretion of inflammatory
      cytokines by PB DCs and monocytes, and could facilitate the development of liver
      disease.

PMID- 23550694
TI  - Effect of self-hypnosis on duration of labor and maternal and neonatal outcomes:
      a randomized controlled trial.
AB  - OBJECTIVE: To examine the effect of a brief course in self-hypnosis for
      childbirth on duration of the labor and other birth outcomes. DESIGN: A
      randomized, controlled, single-blind trial. SETTING: Aarhus University Hospital
      Skejby, Denmark. POPULATION: A total of 1222 healthy nulliparous women. METHODS:
      A hypnosis group receiving three 1-h lessons in self-hypnosis with additional
      audio-recordings to ease childbirth, a relaxation group receiving three 1-h
      lessons in various relaxation methods and mindfulness with audio-recordings for
      additional training, and a usual-care group receiving only the usual antenatal
      care were compared. MAIN OUTCOME MEASURES: Duration of labor, birth
      complications, lactation success, caring for the child, and preferred future mode
      of delivery. RESULTS: No differences were found across the three groups on
      duration from arriving at the birth department until the expulsive phase of
      second stage of labor, the duration of the expulsive phase, or other birth
      outcomes. Fewer emergency and more elective cesarean sections occurred in the
      hypnosis group. No difference was seen across the groups for lactation success or
      caring for the child but fewer women in the hypnosis group preferred a cesarean
      section in future pregnancies because of fear of childbirth and negative birth
      experiences. CONCLUSIONS: Learning self-hypnosis to ease childbirth taught as a
      brief course failed to show any effects on duration of childbirth and other birth
      outcomes.

PMID- 23550695
TI  - Endocrine evaluation after an intra-articular therapeutic dosage of dexamethasone
      in horses.
AB  - This study investigated whether a single intra-articular administration (IA) of
      dexamethasone (DEX) in horses at therapeutic dosage could exert a systemic effect
      by influencing the hypothalamic-pituitary-adrenal axis activity as a consequence
      of (limited) absorption and systemic distribution. The results indicated that DEX
      was detectable in urine collected 12-48 h after IA administration and that
      injection was accompanied by a reduced urine excretion of cortisol, 6beta
      hydroxycortisol (6betaOHF) and two other metabolites of cortisol lasting up to 48
      h post-DEX administration. The systemic effects in horses treated with DEX by IA
      route are similar to those that typically occur with short-term treatment
      including the reduction in urinary cortisol concentration. 

PMID- 23550697
TI  - Diabetes and thyroid cancer mortality: a 12-year prospective follow-up of
      Taiwanese.
AB  - BACKGROUND: The association between diabetes and thyroid cancer is rarely
      studied. This study evaluated thyroid cancer mortality trend in Taiwanese
      population, mortality rate ratios between diabetic patients and general
      population, and risk factors in diabetic patients. METHODS: In general
      population, age-standardized trends were evaluated from 1995 to 2006. A total of
      113,347 diabetic men and 131,573 diabetic women aged >= 25 years recruited during
      1995-1998 were followed to 2006. Age- and sex-specific mortality rate ratios were
      calculated and Cox's regression evaluated the risk factors. RESULTS: A steady
      trend of thyroid cancer mortality was observed in the general population. A total
      of 20 diabetic men and 45 diabetic women died of thyroid cancer, with overall
      mortality rate 2.32 and 4.26 per 100,000 person-years, respectively. Mortality
      rate ratios showed positive association with magnitude increased with decreasing
      age: 1.85 (0.77, 4.43), 1.21 (0.54, 2.73), 2.53 (1.14, 5.59) and 5.80 (2.10,
      16.01) for >= 75, 65-74, 55-64 and 25-54 years old, respectively, for men; and
      0.78 (0.35, 1.74), 2.03 (1.31, 3.13), 2.99 (1.77, 5.04) and 5.34 (2.20, 13.00),
      respectively, for women. After adjustment, only age was significantly associated
      with thyroid cancer mortality. Sex, diabetes duration, diabetes type, body mass
      index, smoking, insulin use and area of residence were not significantly
      predictive for thyroid cancer mortality. CONCLUSIONS: The annual thyroid cancer
      mortality during 1995-2006 in the Taiwanese general population has been steady.
      Our data suggest a higher risk in diabetic patients, with especially higher
      mortality rate ratios in younger age. Obesity, smoking and insulin use are not
      modifiable risk factor.

PMID- 23550698
TI  - Habitat fragmentation and reproductive success: a structural equation modelling
      approach.
AB  - 1. There is great interest on the effects of habitat fragmentation, whereby
      habitat is lost and the spatial configuration of remaining habitat patches is
      altered, on individual breeding performance. However, we still lack consensus of
      how this important process affects reproductive success, and whether its effects
      are mainly due to reduced fecundity or nestling survival. 2. The main reason for
      this may be the way that habitat fragmentation has been previously modelled.
      Studies have treated habitat loss and altered spatial configuration as two
      independent processes instead of as one hierarchical and interdependent process,
      and therefore have not been able to consider the relative direct and indirect
      effects of habitat loss and altered spatial configuration. 3. We investigated how
      habitat (i.e. old forest) fragmentation, caused by intense forest harvesting at
      the territory and landscape scales, is associated with the number of fledged
      offspring of an area-sensitive passerine, the Eurasian treecreeper (Certhia
      familiaris). We used structural equation modelling (SEM) to examine the complex
      hierarchical associations between habitat loss and altered spatial configuration
      on the number of fledged offspring, by controlling for individual condition and
      weather conditions during incubation. 4. Against generally held expectations,
      treecreeper reproductive success did not show a significant association with
      habitat fragmentation measured at the territory scale. Instead, our analyses
      suggested that an increasing amount of habitat at the landscape scale caused a
      significant increase in nest predation rates, leading to reduced reproductive
      success. This effect operated directly on nest predation rates, instead of acting
      indirectly through altered spatial configuration. 5. Because habitat amount and
      configuration are inherently strongly collinear, particularly when multiple
      scales are considered, our study demonstrates the usefulness of a SEM approach
      for hierarchical partitioning of habitat amount vs. habitat configuration in
      landscape ecology that may have bearing on biological conclusions.

PMID- 23550699
TI  - Identification of A*29:47, previously typed as A*29:19, in a Mexican bone marrow
      donor from the state of Hidalgo, Mexico.
AB  - The A*29:47 allele was identified in a Mexican Mestizo unrelated bone marrow
      donor from the state of Hidalgo.

PMID- 23550700
TI  - Raman chirped adiabatic passage probed by X-ray spectroscopy.
AB  - We report a theoretical study of the selective vibrational excitation of a HCl
      molecule achieved by Raman chirped adiabatic passage (RCAP) and probed by X-ray
      photoelectron spectroscopy (XPS). It is demonstrated that HCl can be prepared in
      any vibrational level up to nu = 9 with nearly complete population inversion. We
      explore the effects of both the rotation of the molecule and of the temperature
      on the RCAP process, which is proved to be very robust. Furthermore, we emphasize
      that XPS spectra at the chlorine K-shell threshold show characteristic signatures
      of the populated vibrational level, allowing us to follow the RCAP process. 

PMID- 23550701
TI  - Effects of exposure to 17alpha-ethynylestradiol during sexual differentiation on
      the transcriptome of the African clawed frog (Xenopus laevis).
AB  - Exposure to estrogens during the period of sexual differentiation is known to
      adversely affect the development of testes in African clawed frogs (Xenopus
      laevis), but little is known about molecular changes that coincide with the
      development of altered phenotypes. Therefore, the transcriptome-level effects of
      exposure to 17alpha-ethynylestradiol (EE2) during sexual differentiation of X.
      laevis were evaluated by use of Illumina sequencing coupled with RNA-Seq
      expression analysis. Overall, a number of processes were affected by 17alpha
      ethynylestradiol, including steroid biosynthesis, thyroid hormone signaling and
      metabolism, testicular development, and spermatogenesis. Some of the altered
      pathways, such as thyroid hormone signaling and testicular development, could be
      linked with biological effects on metamorphosis and gonadal phenotypes,
      respectively, that were observed in frogs that were exposed to 17alpha
      ethynylestradiol throughout metamorphosis and the early postmetamorphic period.
      Thus, early changes at the transcriptome-level were predictive of pathologies
      that did not manifest until later in development. To validate the quantitative
      capacity of RNA-Seq, a subset of transcripts identified to have altered
      abundances in individuals exposed to 17alpha-ethynylestradiol was also evaluated
      by use of quantitative polymerase chain reaction (qPCR). While small sample sizes
      (n = 3) limited the ability to draw conclusions pertaining to differences in qPCR
      derived abundances of transcripts between control and exposed tadpoles, there was
      a significant relationship (r(2) = 0.78) between fold-changes for RNA-Seq and
      qPCR.

PMID- 23550702
TI  - Factors affecting red blood cell storage age at the time of transfusion.
AB  - BACKGROUND: Clinical trials are investigating the potential benefit resulting
      from a reduced maximum storage interval for red blood cells (RBCs). The key
      drivers that determine RBC age at the time of issue vary among individual
      hospitals. Although progressive reduction in the maximum storage period of RBCs
      would be expected to result in smaller hospital inventories and reduced blood
      availability, the magnitude of the effect is unknown. STUDY DESIGN AND METHODS:
      Data on current hospital blood inventories were collected from 11 hospitals and
      three blood centers in five nations. A general predictive model for the age of
      RBCs at the time of issue was developed based on considerations of demand for
      RBCs in the hospital. RESULTS: Age of RBCs at issue is sensitive to the following
      factors: ABO group, storage age at the time of receipt by the hospital, the
      restock interval, inventory reserve, mean demand, and variation in demand.
      CONCLUSIONS: A simple model, based on hospital demand, may serve as the basis for
      examining factors affecting the storage age of RBCs in hospital inventories. The
      model suggests that the age of RBCs at the time of their issue to the patient
      depends on factors external to the hospital transfusion service. Any substantial
      change in the expiration date of stored RBCs will need to address the broad
      variation in demand for RBCs while attempting to balance considerations of
      availability and blood wastage.

PMID- 23550704
TI  - Atypical pilar leiomyomatosis: an unusual presentation of multiple atypical
      cutaneous leiomyomas.
AB  - Cutaneous leiomyomas are relatively common benign smooth muscle tumors that may
      arise as solitary or multiple lesions. Rare forms with cytologic atypia, and
      features similar to symplastic leiomyomas of the uterus, have been described. We
      report a case of multiple cutaneous atypical leiomyomas occurring in a 43-year
      old man with long history of lesions of the right lower leg and a family history
      of leiomyomatosis. Twenty of the lesions were excised due to pain and were
      examined histopathologically. All the lesions exhibited features described in
      atypical leiomyomas of the skin including increased cellularity, nuclear atypia
      and pleomorphism, and low mitotic activity. The biologic potential of cutaneous
      atypical leiomyomas is uncertain. Only a few case reports exist in the literature
      with the majority occurring as solitary lesions. Most of the reported atypical
      leiomyomas have behaved in a benign fashion. However, a rare account of
      transformation to leiomyosarcoma emphasizes the need for long-term follow up of
      these patients. Herein, we describe a case of multiple atypical cutaneous
      leiomyomas arising in the setting of familial leiomyomatosis.

PMID- 23550703
TI  - Global analysis of phosphorylation of tau by the checkpoint kinases Chk1 and Chk2
      in vitro.
AB  - Hyperphosphorylation of microtubule-associated protein tau is thought to
      contribute to Alzheimer's disease (AD) pathogenesis. We previously showed that
      DNA damage-activated cell cycle checkpoint kinases Chk1 and Chk2 phosphorylate
      tau at an AD-related site and enhance tau toxicity, suggesting potential roles of
      these kinases in AD. The purpose of this study is to systematically identify
      which sites in tau are directly phosphorylated by Chk1 and Chk2. Using
      recombinant human tau phosphorylated by Chk1 and Chk2 in vitro, we first analyzed
      tau phosphorylation at the AD-related sites by Western blot with phospho-tau
      specific antibodies. Second, to globally identify phosphorylated sites in tau,
      liquid chromatography-tandem mass spectrometry (LC-MS(3)) was employed. These
      systematic analyses identified a total of 27 Ser/Thr residues as Chk1- or Chk2-
      target sites. None of them were proline-directed kinase targets. Many of these
      sites are located within the microtubule-binding domain and C-terminal domain,
      whose phosphorylation has been shown to reduce tau binding to microtubules and/or
      has been implicated in tau toxicity. Among these 27 sites, 13 sites have been
      identified to be phosphorylated in AD brains. Since DNA damage is accumulated in
      diseased brains, Chk1 and Chk2 may be involved in tau phosphorylation and
      toxicity in AD pathogenesis.

PMID- 23550705
TI  - Early traumatic events in psychopaths.
AB  - The relationship between diverse early traumatic events and psychopathy was
      studied in 194 male inmates. Criminal history transcripts were revised, and
      clinical interviews were conducted to determine the level of psychopathy using
      the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory
      was applied to assess the incidence of abuse before 18 years of age. Psychopathic
      inmates presented a higher victimization level and were more exposed to certain
      types of intended abuse than sociopathic inmates, while the sum of events and
      emotional abuse were associated with the PCL-R score. Our studies support the
      influence of early adverse events in the development of psychopathic offenders.

PMID- 23550706
TI  - Global diversity and distribution of three necrotrophic effectors in
      Phaeosphaeria nodorum and related species.
AB  - Population genetic and phylogenetic studies have shown that Phaeosphaeria nodorum
      is a member of a species complex that probably shares its center of origin with
      wheat (Triticum aestivum and Triticum durum). We examined the evolutionary
      histories of three known necrotrophic effectors (NEs) produced by P. nodorum and
      compared them with neutral loci. We screened over 1000 individuals for the
      presence/absence of each effector and assigned each individual to a multi
      effector genotype. Diversity at each NE locus was assessed by sequencing c. 200
      individuals for each locus. We found significant differences in effector
      frequency among populations. We propose that these differences reflect the
      presence/absence of the corresponding susceptibility gene in wheat cultivars. The
      population harboring the highest sequence diversity was different for each
      effector locus and never coincided with populations harboring the highest
      diversity at neutral loci. Coalescent and phylogenetic analyses showed a
      discontinuous presence of all three NEs among nine closely related Phaeosphaeria
      species. Only two of the nine species were found to harbor NEs. We present
      evidence that the three described NEs of P. nodorum were transmitted to its
      sister species, Phaeosphaeria avenaria tritici 1, via interspecific
      hybridization.

PMID- 23550707
TI  - Gastrocnemius tendon strain in a dog treated with autologous mesenchymal stem
      cells and a custom orthosis.
AB  - OBJECTIVE: To report clinical findings and outcome in a dog with gastrocnemius
      tendon strain treated with autologous mesenchymal stem cells and a custom
      orthosis. STUDY DESIGN: Clinical report. ANIMAL: A 4-year-old spayed female
      Border Collie. METHODS: Bone-marrow derived, autologous mesenchymal stem cells
      were transplanted into the tendon core lesion. A custom, progressive, dynamic
      orthosis was fit to the tarsus. Serial orthopedic examinations and
      ultrasonography as well as long-term force-plate gait analysis were utilized for
      follow up. RESULTS: Lameness subjectively resolved and peak vertical force
      increased from 43% to 92% of the contralateral pelvic limb. Serial
      ultrasonographic examinations revealed improved but incomplete restoration of
      normal linear fiber pattern of the gastrocnemius tendon. CONCLUSIONS: Findings
      suggest that autologous mesenchymal stem cell transplantation with custom,
      progressive, dynamic orthosis may be a viable, minimally invasive technique for
      treatment of calcaneal tendon injuries in dogs.

PMID- 23550708
TI  - Deconstructing Ixodes ricinus: a partial matrix model allowing mapping of tick
      development, mortality and activity rates.
AB  - A stage-structured Leslie matrix model of a partial, discrete population of
      Ixodes ricinus (Linnaeus) (Ixodida: Ixodidae) ticks was developed to elucidate
      the impact of climate trends on the distribution and phenology of this species in
      the western Palaearctic. The model calculates development and mortality rates for
      each instar and evaluates recruitment rates based on the development of the tick
      population. The model captures the changes in development and mortality rates,
      providing a coherent index of performance correlated with the tick's geographic
      range. Maximum development rates are recorded for latitudes south of 36  degrees
      N and are spatially correlated with sites of maximum temperature, highest
      saturation deficit and highest mortality. The maximum available developmental
      time (the total annual time during which temperature allows development) for I.
      ricinus in the western Palaearctic is < 45% of the total year. North of 60 
      degrees N, available developmental time decreases sharply to only 15% of the
      year. The latitudinal boundary at which survival rates sharply drop is 43-46 
      degrees N, clearly delimiting the classically recognized extent of the main tick
      populations. The pattern of activity for larval-nymphal synchrony shows a clear
      west-east pattern. The model demonstrates the impact of climate according to tick
      stage and geographic location, and provides a practical framework for testing how
      the tick's lifecycle is affected by climate change. 

PMID- 23550709
TI  - The effect of non-dipper and dipper blood pressure patterns on aortic elasticity
      in patients with metabolic syndrome.
AB  - The purpose of this study was to evaluate the effect of blood pressure (BP)
      rhythm on aortic functions in patients with metabolic syndrome. Seventy patients
      with newly diagnosed hypertension who fulfilled the metabolic syndrome criteria
      according to the Third Report of the National Cholesterol Education Program
      Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
      Adults (NCEP/ATP-III) were evaluated with 24-hour BP holter monitoring. According
      to BP rhythm, 35 patients with dipper BP pattern and 35 patients with non-dipper
      BP pattern were enrolled as two groups in our study. Systolic and diastolic
      diameters of the ascending aorta were measured by M-mode echocardiography and
      aortic functions (aortic strain, distensibility, and stiffness index) were
      calculated. The nocturnal systolic and diastolic BPs were significantly higher in
      non-dipper patients than the dipper group. According to clinical parameters
      including age, gender, height, weight, body mass index, waist circumference,
      clinical systolic, and diastolic BPs, we did not find significantly difference
      between the two groups. Aortic strain was significantly higher (6.63 +/- 3.37 vs.
      1.81 +/- 0.92; P < .0001) and aortic distensibility was lower (2.38 +/- 1.18 cm(
      2)/dyn/10(-6) and 6.66 +/- 3.67 cm(-2)/dyn/10(-6); P < .001) in non-dipper group.
      These findings suggest that aortic functions were prominently deteriorated in non
      dipper hypertensive patients than dippers with metabolic syndrome.

PMID- 23550710
TI  - Current and future options for the diagnosis of malignant pleural effusion.
AB  - INTRODUCTION: Malignant pleural effusion (MPE) is a frequent problem faced by
      clinicians, but tumor pleural involvement can be seen without effusion. AREAS
      COVERED: Imaging, pleural fluid analysis, biomarkers for MPE, needle pleural
      biopsy and thoracoscopy. To prepare this review, we performed a search using
      keywords: 'diagnosis' + 'malignant' + 'pleural' + 'effusion' (all fields) in
      PubMed, and found 4106 articles overall (until 16 January 2013, 881 in the last 5
      years). EXPERT OPINION: Ultrasound techniques will stay as valuable tools for
      pleural effusions. Biomarkers in pleural fluid do not currently provide an
      acceptable yield for MPE. In subjects with past history of asbestos exposure,
      some serum or plasma markers (soluble mesothelin, fibulin) might help in
      selecting cases for close follow-up, to detect mesothelioma early. Needle pleural
      biopsy is justified only if used with image-techniques (ultrasound or CT)
      guidance, and thoracoscopy is better for both diagnosis and immediate palliative
      treatment (pleurodesis). Animal models of MPE and 'spheroids' are promising for
      research involving both pathophysiology and therapy. Considering the possibility
      of direct pleural delivery of nanotechnology-developed compounds-fit to both
      diagnosis and therapy purposes ('theranostics')-MPE and mesothelioma in
      particular are likely to benefit sooner than later from this exciting
      perspective.

PMID- 23550713
TI  - Time to rehospitalization of schizophrenia patients with alcohol use disorders.

PMID- 23550712
TI  - The impact of adolescent binge drinking and sustained abstinence on affective
      state.
AB  - BACKGROUND: While it is clear that affect is negatively impacted by heavy
      drinking in adulthood and that it improves with abstinence, little is known about
      effects of heavy drinking on mood during adolescence. METHODS: This study
      examined negative mood states among 2 groups of 16- to 18-year-old high school
      students; youth with a history of recent heavy episodic drinking (HED; n = 39)
      and comparison youth with limited lifetime drinking experience (CON; n = 26).
      Affect was assessed at 3 time points during a 4- to 6-week period of monitored
      abstinence using the Hamilton Rating Scales for Anxiety and Depression; self
      reports were obtained with the state portion of the State-Trait Anxiety
      Inventory, and experience sampling of current affect was assessed via daily text
      messages sent at randomly determined times in the morning, afternoon, and
      evening. RESULTS: Youth with a recent history of HED reported more negative
      affect compared with nondrinking youth during early stages of abstinence (days
      since last HED at assessment 1: M = 6.46; SD = 5.06); however, differences in
      affect were not observed after 4 to 6 weeks of abstinence. Sex differences were
      evident, with HED girls reporting greater depression and anxiety than HED male
      peers. Although not significant, response patterns indicated that boys may
      experience faster resolution of negative emotional states than girls with
      sustained abstinence. CONCLUSIONS: Findings suggest that high-dose drinking is
      associated with elevated negative affect for adolescents and that negative mood
      states may take longer to resolve for girls than for boys following heavy
      drinking episodes. Future research clarifying naturally occurring changes in
      affective response during early and sustained abstinence is necessary for
      improving programs designed to promote adolescent decision-making and to reduce
      risk for relapse.

PMID- 23550714
TI  - The European Medicines Agency approval of 5-aminolaevulinic acid (Ameluz) for the
      treatment of actinic keratosis of mild to moderate intensity on the face and
      scalp: summary of the scientific assessment of the Committee for Medicinal
      Products for Human Use.
AB  - The European Commission has recently issued a marketing authorisation valid
      throughout the European Union for 5-aminolaevulinic acid (Ameluz). The decision
      was based on the favorable opinion of the CHMP recommending a marketing
      authorization for 5-aminolaevulinic acid for treatment of actinic keratosis of
      mild to moderate intensity on the face and scalp. The active substance is a
      sensitizer used in photodynamic/radiation therapy (ATC code L01XD04). The gel
      should cover the lesions and approximately 5 mm of the surrounding area with a
      film of about 1 mm thickness. The entire treatment area should be illuminated
      with a red light source, either with a narrow spectrum around 630 nm and a light
      dose of approximately 37 J/cm(2) or a broader and continuous spectrum in the
      range between 570 and 670 nm with a light dose between 75 and 200 J/cm(2). One
      session of photodynamic therapy should be administered for single or multiple
      lesions. Non- or partially responding lesions should be retreated in a second
      session 3 months after the first treatment. 5-aminolaevulinic acid is metabolized
      to protoporphyrin IX, a photoactive compound which accumulates intracellularly in
      the treated actinic keratosis lesions. Protoporphyrin IX is activated by
      illumination with red light of a suitable wavelength and energy. In the presence
      of oxygen, reactive oxygen species are formed which causes damage of cellular
      components and eventually destroys the target cells. The benefit with 5
      aminolaevulinic acid is its ability to improve the complete response rate of
      actinic keratosis lesions. The most common side effects are reactions at the site
      of application. The objective of this article is to summarize the scientific
      review of the application. The detailed scientific assessment report and product
      information, including the summary of product characteristics (SmPC), are
      available on the EMA website (www.ema.europa.eu).

PMID- 23550715
TI  - Plasma and tissue pharmacokinetics of marbofloxacin in experimentally infected
      chickens with Mycoplasma gallisepticum and Escherichia coli.
AB  - The plasma and tissue pharmacokinetics of marbofloxacin in chickens
      experimentally infected with Mycoplasma gallisepticum and Escherichia coli were
      studied. Marbofloxacin was given to 66 infected chickens by oral administration
      at a dosage of 5 mg/kg b.w., once a day for three days. Plasma, brain, kidney,
      liver, lung, muscle and trachea were collected and marbofloxacin concentrations
      were analyzed by a high performance liquid chromatography method. In the infected
      chickens, maximal marbofloxacin concentrations in plasma, brain, kidney, liver,
      lung, muscle and trachea were 1.84, 1.33, 7.35, 5.61, 3.12, 2.98, and 4.51 g/mL
      (g); the elimination half-lives of marbofloxacin were 6.8, 2.74, 9.31, 8.45,
      9.55, 11.53 and 5.46 h for plasma, brain, kidney, liver, lung, muscle and
      trachea, respectively. AUC were calculated to be 9.68, 8.04, 45.1, 27.03, 20.56,
      19.47, and 32.68 MUg/mL (g) for plasma, brain, kidney, liver, lung, muscle and
      trachea, respectively. Marbofloxacin concentration in tissues except for brain
      exceeded marbofloxacin concentration in plasma, with AUC(tissue) /AUC(plasma)
      ranging from 2.01 to 4.66 and Peak(tissue) /Peak(plasma) ranging from 1.62 to
      3.99. The results showed that a marbofloxacin dosage of 5 mg/kg administered
      orally at 24 h intervals may provide successful treatment of chicken with MG and
      E. coli infection.

PMID- 23550716
TI  - Stroke volume-directed administration of hydroxyethyl starch or Ringer's acetate
      in sitting position during craniotomy.
AB  - BACKGROUND: To determine the volumes required for stable haemodynamics and
      possible effects on the coagulation, we studied stroke volume (SV)-directed
      administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate
      (RAC) in neurosurgical patients operated on in a sitting position. METHODS:
      Thirty craniotomy patients were randomised to receive either HES or RAC. Before
      positioning, SV, measured by arterial pressure waveform analysis, was maximised
      by boluses of fluid until SV did not increase more than 10%. SV was maintained by
      repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups during
      surgery. RESULTS: Comparable haemodynamics were achieved with the mean [standard
      deviation (SD)] cumulative doses of HES or RAC 271 (47) or 264 (50) ml (P =
      0.699) before the sitting position. Mean (SD) doses of HES or RAC at 30 min after
      the positioning were 343 (94) or 450 (156) ml (P = 0.036), and at the end of
      surgery 464 (284) or 707 (425) ml, respectively (P = 0.087). The intraoperative
      fluid balance was more positive in the RAC than in the HES group [P = 0.044, 95%
      confidence interval (CI) -978 to -14]. Cardiac and stroke volume indexes [CI and
      stroke volume index (SVI)] increased in the HES group (P < 0.05) but not in the
      RAC group [non significant (N.S.)]. Neither coagulation profile nor blood loss
      differed between the groups. CONCLUSION: Fluid filling with HES boluses resulted
      in a positive response in CI and SVI during the sitting position. The 34% smaller
      volume of HES than crystalloid and less positive fluid balance in the HES group
      might be important in craniotomy patients with decreased brain compliance.

PMID- 23550717
TI  - Exploiting plasmon-induced hot electrons in molecular electronic devices.
AB  - Plasmonic nanostructures can induce a number of interesting responses in devices.
      Here we show that hot electrons can be extracted from plasmonic particles and
      directed into a molecular electronic device, which represents a new mechanism of
      transfer from light to electronic transport. To isolate this phenomenon from
      alternative and sometimes simultaneous mechanisms of plasmon-exciton
      interactions, we designed a family of hybrid nanostructure devices consisting of
      Au nanoparticles and optoelectronically functional porphyin molecules that enable
      precise control of electronic and optical properties. Temperature- and wavelength
      dependent transport measurements are analyzed in the context of optical
      absorption spectra of the molecules, the Au particle arrays, and the devices.
      Enhanced photocurrent associated with exciton generation in the molecule is
      distinguished from enhancements due to plasmon interactions. Mechanisms of
      plasmon-induced current are examined, and it is found that hot electron
      generation can be distinguished from other possibilities.

PMID- 23550718
TI  - Bergmann's rule across the equator: a case study in Cerdocyon thous (Canidae).
AB  - 1. The variation in cranial size of the crab-eating fox Cerdocyon thous was
      analysed in relation to latitude and several environmental variables throughout
      its distribution in South America. 2. We tested the existence of clines to
      determine whether this canid follows Bergmann's rule to the north and south of
      the Equator. Also, using niche modelling, we analysed whether the climatic
      changes during the last glaciation could have influenced Bergmann's rule in this
      species. We quantified the size of the cranium of C. thous (n = 300). The data
      were divided into two groups: (i) south of the Equator (n = 163) and (ii) north
      of the Equator (n = 137). We performed correlations, OLS regressions and
      simultaneous autoregressions to analyse the relationship between the variation in
      size and different geographic and environmental variables. Data of occurrence (n
      = 594) together with ambient variables from the present and the last glacial
      maximum (LGM) were used to predict the occurrence of C. thous with the
      implementation of the maximum entropy method. Present-day and historical
      distribution maps were obtained. 3. The variation in the size of the cranium of
      C. thous showed two trends. In the south of Equator, we observed that the size of
      the skull shows an inverse relationship with temperature-related variables and a
      positive one with precipitation, while in north of the Equator, we observed the
      opposite relationship. Populations south of the Equator follow Bergmann's rule
      showing increasing size with increasing latitude. To the north of the Equator, a
      non-Bergmannian pattern occurs because size decreases with increasing latitude.
      4. Niche modelling showed two present-day groupings in South America, one north
      of Amazonia and the other south. However, for the period of the LGM, four groups
      emerged, possibly related to the four subspecies presently described for C.
      thous. Therefore, it is possible that the observed pattern - southern populations
      following Bergmann's rule while northern populations reflecting the opposite -
      has been influenced by the events that occurred during the LGM that could have
      led to the differentiation of populations.

PMID- 23550719
TI  - Financial, nonfinancial and editors' conflicts of interest in high-impact
      biomedical journals.
AB  - PURPOSE: To assess financial, nonfinancial and editors' conflicts of interest
      (COI) disclosure policies among the most influential biomedical journals
      publishing original research. MATERIALS AND METHODS: We conducted a cross
      sectional study of 399 high-impact biomedical journals in 27 biomedical
      categories of the Journal Citation Reports (JCR) in December 2011. Information
      relevant to COI and requirements for disclosures that was publicly available on
      journal websites was collected. RESULTS: While financial COI disclosures were
      required by 358 (89.7%) and nonfinancial by 280 (70.2%) journals, 155 (38.8%)
      required editors' disclosures. Journals in the first decile of the JCR
      classification scored significantly higher than those in the second decile for
      all disclosure policies. Ninety (22.6%) journals were published by Elsevier and
      59 (14.8%) by Wiley-Blackwell, with Elsevier scoring significantly better in
      financial disclosure policies (P = 0.022). Clinical journals scored significantly
      higher than basic journals for all disclosure policies. No differences were
      observed between open-access (n = 25) and nonopen-access (n = 374) journals for
      any type of disclosure. Somewhat incoherently, authors' disclosure statements
      were included in some published manuscript in 57.1% of journals without any COI
      disclosure policies. CONCLUSIONS: Authors' financial COI disclosures were
      required by about 90% of high-impact clinical and basic journals publishing
      original research. Unlike recent studies showing a significantly lower prevalence
      of nonfinancial compared with financial disclosures, the former were required by
      about 70% of journals, suggesting that editors are increasingly concerned about
      nonfinancial competing interests. Only 40% of journals required disclosure of
      editors' COI, in conflict with the recommendations of the most influential
      editors' associations.

PMID- 23550720
TI  - Tripartin, a histone demethylase inhibitor from a bacterium associated with a
      dung beetle larva.
AB  - Tripartin (1), a new dichlorinated indanone, was isolated from the culture broth
      of the Streptomyces sp. associated with a larva of the dung beetle Copris
      tripartitus Waterhouse. The planar structure of tripartin (1) was identified by
      the spectroscopic analyses of NMR, mass, UV, and IR data. The structure was
      confirmed, and the absolute configuration of 1 was determined by X-ray
      crystallography. Tripartin displayed specific activity as an inhibitor of the
      histone H3 lysine 9 demethylase KDM4 in HeLa cells.

PMID- 23550721
TI  - Next-generation sequencing: proof of concept for antenatal prediction of the
      fetal Kell blood group phenotype from cell-free fetal DNA in maternal plasma.
AB  - BACKGROUND: Maternal immunization against KEL1 of the Kell blood group system can
      have serious adverse consequences for the fetus as well as the newborn baby.
      Therefore, it is important to determine the phenotype of the fetus to predict
      whether it is at risk. We present data that show the feasibility of predicting
      the fetal KEL1 phenotype using next-generation sequencing (NGS) technology. STUDY
      DESIGN AND METHODS: The KEL1/2 single-nucleotide polymorphism was polymerase
      chain reaction (PCR) amplified with one adjoining base, and the PCR product was
      sequenced using a genome analyzer (GAIIx, Illumina); several millions of PCR
      sequences were analyzed. RESULTS: The results demonstrated the feasibility of
      diagnosing the fetal KEL1 or KEL2 blood group from cell-free DNA purified from
      maternal plasma. CONCLUSION: This method requires only one primer pair, and the
      large amount of sequence information obtained allows well for statistical
      analysis of the data. This general approach can be integrated into current
      laboratory practice and has numerous applications. Besides DNA-based predictions
      of blood group phenotypes, platelet phenotypes, or sickle cell anemia, and the
      determination of zygosity, various conditions of chimerism could also be examined
      using this approach. To our knowledge, this is the first report focused on
      antenatal blood group determination using NGS.

PMID- 23550722
TI  - Thermal stability of peroxy acyl nitrates formed in the oxidation of
      C(x)F(2x+1)CH2C(O)H (x = 1,6) in the presence of NO2.
AB  - The formation of C(x)F(2x+1)CH2C(O)OONO2 (x = 1,6) from the photooxidation of
      C(x)F(2x+1)CH2C(O)H (x = 1,6) in the presence of NO2 was investigated. The
      infrared spectrum of C6F13CH2C(O)OONO2 is reported for the first time, and
      thermal stability for both peroxynitrates at 295 K and 9.0 mbar is informed.
      Kinetic parameters (activation energy and pre-exponential factor) for
      CF3CH2C(O)OONO2 at 9.0 and 1000 mbar are: 108 +/- 2 kJ/mol, 1.5 * 10(15) and 114
      +/- 2 kJ/mol, 2.4 * 10(16), respectively. A comparison is made between fluoro and
      hydrogenated peroxy acyl nitrates.

PMID- 23550723
TI  - Proteomic analysis of human bronchoalveolar lavage fluid after subsgemental
      exposure.
AB  - The analysis of airway fluid, as sampled by bronchoalveolar lavage (BAL),
      provides a minimally invasive route to interrogate lung biology in health and
      disease. Here, we used immunodepletion, coupled with gel- and label-free LC
      MS/MS, for quantitation of the BAL fluid (BALF) proteome in samples recovered
      from human subjects following bronchoscopic instillation of saline,
      lipopolysaccharide (LPS) or house dust mite antigen into three distinct lung
      subsegments. Among more than 200 unique proteins quantified across nine samples,
      neutrophil granule-derived and acute phase proteins were most highly enriched in
      the LPS-exposed lobes. Of these, peptidoglycan response protein 1 was validated
      and confirmed as a novel marker of neutrophilic inflammation. Compared to a prior
      transcriptomic analysis of airway cells in this same cohort, the BALF proteome
      revealed a novel set of response factors. Independent of exposure, the enrichment
      of tracheal-expressed proteins in right lower lung lobes suggests a potential for
      constitutive intralobar variability in the BALF proteome; sampling of multiple
      lung subsegments also appears to aid in the identification of protein signatures
      that differentiate individuals at baseline. Collectively, this proof-of-concept
      study validates a robust workflow for BALF proteomics and demonstrates the
      complementary nature of proteomic and genomic techniques for investigating airway
      (patho)physiology.

PMID- 23550725
TI  - Unilesional self-limited Langerhans cell histiocytosis: a case report and review
      of the literature.
AB  - Self-limited Langerhans cell histiocytosis (LCH) represents a rare, congenital,
      cutaneous form of LCH associated with a good prognosis. Only 35 cases of solitary
      lesion self-limited LCH have been reported. Herein, we present an additional case
      in a 3-month-old boy who presented with an isolated pigmented nodule on his left
      posterior shoulder, which had been present since birth. Punch biopsy showed
      histopathologic features of LCH with positive CD1a and CD68 stains. Further
      examination and investigation showed no features of systemic involvement. The
      lesion spontaneously resolved within 2 months, and there has been no evidence of
      recurrence on follow up. As several cases of recurrence and complications have
      been reported in self-limited LCH, we emphasize the need for long-term, and
      perhaps indefinite, follow up for symptoms and signs associated with LCH in these
      patients.

PMID- 23550724
TI  - Cannabidiol attenuates deficits of visuospatial associative memory induced by
      Delta(9) tetrahydrocannabinol.
AB  - BACKGROUND AND PURPOSE: Recent human studies suggest that recreational cannabis
      strains that are relatively high in cannabidiol (CBD) content produce less
      cognitive impairment than do strains with negligible CBD and similar Delta(9)
      tetrahydrocannabinol (THC) content. Self-selection in such studies means it is
      impossible to rule out additional variables which may determine both cannabis
      strain selection and basal cognitive performance level. Controlled laboratory
      studies can better determine a direct relationship. EXPERIMENTAL APPROACH: In
      this study, adult male rhesus monkeys were assessed on visuospatial Paired
      Associates Learning and Self-Ordered Spatial Search memory tasks, as well as
      additional tests of motivation and manual dexterity. Subjects were challenged
      with THC (0.2, 0.5 mg.kg(-1) , i.m.) in randomized order and evaluated in the
      presence or absence of 0.5 mg.kg(-1) CBD. KEY RESULTS: CBD attenuated the effects
      of THC on paired associates learning and a bimanual motor task without affecting
      the detrimental effects of THC on a Self-Ordered Spatial Search task of working
      memory. CBD did not significantly reverse THC-induced impairment of a progressive
      ratio or a rotating turntable task. CONCLUSIONS AND IMPLICATIONS: This study
      provides direct evidence that CBD can oppose the cognitive-impairing effects of
      THC and that it does so in a task-selective manner when administered
      simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing
      therapeutic products may therefore help to ameliorate unwanted cognitive side
      effects. LINKED ARTICLE: This article is commented on by Mechoulam and Parker, pp
      1363-1364 of this issue. To view this commentary visit
      http://dx.doi.org/10.1111/bph.12400.

PMID- 23550726
TI  - Discrete traits of the sternum and ribs: a useful contribution to identification
      in forensic anthropology and medicine.
AB  - During forensic anthropological investigation, biological profile is determined
      by age, sex, ancestry, and stature. However, several individuals may share the
      same profile. Observation of discrete traits can yield useful information and
      contribute to identification. This research establishes the frequency of discrete
      traits of the sternum and ribs in a modern population in southern France, using
      500 computer tomography (CT) scans of individuals aged 15-60 years. Only discrete
      traits with a frequency lower than 10% according to the literature were
      considered, a total of eight traits. All scans examined were three-dimensional
      (3D) volume renderings from DICOM images. In our population, the frequency of all
      the discrete traits was lower than 5%. None were associated with sex or age, with
      the exception of a single trait, the end of the xiphoid process. Our findings can
      usefully be applied for identification purposes in forensic anthropology and
      medicine.

PMID- 23550727
TI  - Identification of tetrabromobisphenol A allyl ether and tetrabromobisphenol A 2,3
      dibromopropyl ether in the ambient environment near a manufacturing site and in
      mollusks at a coastal region.
AB  - Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame
      retardants (BFRs) and has been frequently detected in the environment and biota.
      Recent studies have found that derivatives of TBBPA, such as TBBPA bis(allyl)
      ether (TBBPA BAE) and TBBPA bis(2,3-dibromopropyl) ether (TBBPA BDBPE) are
      present in various environmental compartments. In this work, using liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS) and liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF
      MS), TBBPA allyl ether (TBBPA AE) and TBBPA 2,3-dibromopropyl ether (TBBPA DBPE)
      were identified in environmental samples and further confirmed by synthesized
      standards. Soil, sediment, rice hull, and earthworm samples collected near a BFR
      manufacturing plant were found to contain these two compounds. In sediments, the
      concentrations of TBBPA AE and TBBPA DBPE ranged from 1.0 to 346.6 ng/g of dry
      weight (dw) and from 0.7 to 292.7 ng/g of dw, respectively. TBBPA AE and TBBPA
      DBPE in earthworm and rice hull samples were similar to soil samples, which
      ranged from below the method limit of detection (LOD, <0.002 ng/g of dw) to 0.064
      ng/g of dw and from below the LOD (<0.008 ng/g of dw) to 0.58 ng/g of dw,
      respectively. Furthermore, mollusks collected from the Chinese Bohai Sea were
      used as a bioindicator to investigate the occurrence and distribution of these
      compounds in the coastal environment. The detection frequencies of TBBPA AE and
      TBBPA DBPE were 41 and 32%, respectively, and the concentrations ranged from
      below LOD (<0.003 ng/g of dw) to 0.54 ng/g of dw, with an average of 0.09 ng/g of
      dw, for TBBPA AE, and from below LOD (<0.008 ng/g of dw) to 1.41 ng/g of dw, with
      an average of 0.15 ng/g of dw, for TBBPA DBPE.

PMID- 23550728
TI  - Spectroscopic and mechanical evaluation of thin film commonly used for banding
      congenital portosystemic shunts in dogs.
AB  - OBJECTIVES: To (1) determine whether different types of thin film used to occlude
      congenital portosystemic shunts are cellophane, and (2) evaluate the influence of
      saline immersion and sterilization on the tensile properties of cellophane. STUDY
      DESIGN: Ex vivo spectroscopic evaluation and mechanical testing. SAMPLE
      POPULATION: Rectangular strips of thin film from 4 sources. METHODS: Samples were
      evaluated with Fourier Transform Infrared Spectroscopy and microscopy with a
      polarizing lens. Samples consistent with cellophane were divided into 5
      sterilization groups: non-sterile, autoclave, gamma irradiation, hydrogen
      peroxide and ethylene oxide. Samples were tested while dry or after saline
      solution immersion. Tensile properties were compared using ANOVA, unpaired t
      tests, Mann-Whitney U-tests and Fisher's exact tests. P < 0.05 was considered
      significant. RESULTS: One thin film was consistent with cellophane and it could
      be differentiated from the other thin films by visible striations. Cellophane was
      strongest when strips were oriented parallel with its fiber direction and saline
      immersion reduced its strength by 48% (P < .001). All sterilization methods
      except autoclave significantly weakened wet cellophane (ethylene oxide [P <
      .001], gamma irradiation [P < .001], and hydrogen peroxide [P < .001]).
      CONCLUSIONS: Thin film from most sources was not consistent with cellophane.
      Autoclave sterilization is the best way to preserve the strength of wet
      cellophane.

PMID- 23550729
TI  - Inter-species protein trafficking endows dodder (Cuscuta pentagona) with a host
      specific herbicide-tolerant trait.
AB  - . Besides photosynthates, dodder (Cuscuta spp.) acquires phloem-mobile proteins
      from host; however, whether this could mediate inter-species phenotype transfer
      was not demonstrated. Specifically, we test whether phosphinothricin acetyl
      transferase (PAT) that confers host plant glufosinate herbicide tolerance
      traffics and functions inter-specifically. . Dodder tendrils excised from hosts
      can grow in vitro for weeks or resume in vivo by parasitizing new hosts. The
      level of PAT in in vivo and in vitro dodder tendrils was quantified by enzyme
      linked immunosorbent assay. The glufosinate sensitivity was examined by dipping
      the distal end of in vivo and in vitro tendrils, growing on or excised from
      LibertyLink (LL; PAT-transgenic and glufosinate tolerant) and conventional (CN;
      glufosinate sensitive) soybean hosts, into glufosinate solutions for 5 s. After
      in vitro tendrils excised from LL hosts reparasitized new CN and LL hosts, the
      PAT level and the glufosinate sensitivity were also examined. . When growing on
      LL host, dodder tolerated glufosinate and contained PAT at a level of 0.3% of
      that encountered in LL soybean leaf. After PAT was largely degraded in dodders,
      they became glufosinate sensitive. PAT mRNA was not detected by reverse
      transcription PCR in dodders. . In conclusion, the results indicated that PAT
      inter-species trafficking confers dodder glufosinate tolerance.

PMID- 23550730
TI  - Cellular transitions and tissue engineering.
AB  - Epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal
      transition (EndMT) describe complex changes in progenitor lineage, cell
      morphology, and gene expression. Stimulated by environmental cues, these cellular
      transitions are essential for elements of embryonic development and can be
      pathologically dysregulated in disease states. EMT occurs in biological processes
      such as gastrulation, cardiogenesis, and fibrosis. EndMT is involved in
      development and tissue fibrosis, but recent studies have implicated this process
      in musculoskeletal biology and pathology. Tissue engineering and regenerative
      medicine typically rely on endogenous progenitors or progenitors expanded ex vivo
      to repair damaged or impaired tissues or organs. The processes of EMT and EndMT
      may aid in elucidating new methods for reducing fibrosis and identifying novel
      plastic progenitor populations for tissue repair. This review will discuss the
      potential for EMT and EndMT to impact on tissue engineering and regenerative
      medicine.

PMID- 23550731
TI  - Oct4 promoter activity in stem cells obtained through somatic reprogramming.
AB  - Multiple methods exist that can reprogram differentiated cells to a pluripotent
      state similar to that of embryonic stem cells (ESCs). These include somatic cell
      nuclear transfer (SCNT), fusion-mediated reprogramming (FMR) of somatic cells
      with ESCs, and the production of induced pluripotent stem cells (iPSCs). All of
      these methods yield cells in which the endogenous Oct4 gene is reactivated. We
      were interested in comparing the activity of the Oct4 promoter in three different
      classes of pluripotent cells, including normal ESCs, FMR cells (FMRCs), and
      iPSCs. We prepared cells of all three types that harbor a transgene composed of
      the mouse Oct4 promoter driving green fluorescent protein (Oct4-GFP). All cell
      derivations started with a characterized transgenic Oct4-GFP mouse, and from this
      we derived ESCs, FMRCs, and iPSCs with the Oct4-GFP transgene present in an
      identical genomic integration site in all three cell types. Using flow cytometry
      we assessed Oct4 promoter expression, cell cycle behavior, and differentiation
      kinetics. We found similar levels of GFP expression in all three cell types and
      no significant alterations in pluripotency or differentiation. Our results
      suggest that the pluripotent condition is a potent "local attractor" state,
      because it can be achieved through three vastly different avenues.

PMID- 23550732
TI  - Generation of neural cells from DM1 induced pluripotent stem cells as cellular
      model for the study of central nervous system neuropathogenesis.
AB  - Dystrophia myotonica type 1 (DM1) is an autosomal dominant multisystem disorder.
      The pathogenesis of central nervous system (CNS) involvement is poorly
      understood. Disease-specific induced pluripotent stem cell (iPSC) lines would
      provide an alternative model. In this study, we generated two DM1 lines and a
      normal iPSC line from dermal fibroblasts by retroviral transduction of Yamanaka's
      four factors (hOct4, hSox2, hKlf4, and hc-Myc). Both DM1 and control iPSC clones
      showed typical human embryonic stem cell (hESC) growth patterns with a high
      nuclear-to-cytoplasm ratio. The iPSC colonies maintained the same growth pattern
      through subsequent passages. All iPSC lines expressed stem cell markers and
      differentiated into cells derived from three embryonic germ layers. All iPSC
      lines underwent normal neural differentiation. Intranuclear RNA foci, a hallmark
      of DM1, were detected in DM1 iPSCs, neural stem cells (NSCs), and terminally
      differentiated neurons and astrocytes. In conclusion, we have successfully
      established disease-specific human DM1 iPSC lines, NSCs, and neuronal lineages
      with pathognomonic intranuclear RNA foci, which offer an unlimited cell resource
      for CNS mechanistic studies and a translational platform for therapeutic
      development.

PMID- 23550733
TI  - Atomic resolution imaging of grain boundary defects in monolayer chemical vapor
      deposition-grown hexagonal boron nitride.
AB  - Grain boundaries are observed and characterized in chemical vapor deposition
      grown sheets of hexagonal boron nitride (h-BN) via ultra-high-resolution
      transmission electron microscopy at elevated temperature. Five- and seven-fold
      defects are readily observed along the grain boundary. Dynamics of strained
      regions and grain boundary defects are resolved. The defect structures and the
      resulting out-of-plane warping are consistent with recent theoretical model
      predictions for grain boundaries in h-BN.

PMID- 23550734
TI  - Assessment of ultraviolet-radiation-induced DNA damage within melanocytes in skin
      of different constitutive pigmentation.
AB  - BACKGROUND: Melanoma incidence and pigmentary disorders are known to be related
      to the degree of skin pigmentation, but few data exist on the specific impact of
      ultraviolet radiation (UVR) on melanocytes in skin of different constitutive
      pigmentation. OBJECTIVES: To analyse UVR-induced DNA damage within melanocytes in
      different skin-colour types. METHODS: Skin samples were objectively classified
      into light, intermediate, tan, brown and dark skin according to their individual
      typology angle ( degrees ITA), based on colorimetric parameters. Samples were
      exposed to increasing doses of solar simulated radiation. Detection of DNA damage
      specifically in melanocytes was achieved by cyclobutane thymine dimer (CPD)
      tyrosinase-related protein 1 double staining. RESULTS: For light, intermediate
      and tan skin, accumulation of CPDs in melanocytes was detected at the lowest
      dose, with a steep increase with dose. At estimated erythemally equivalent doses,
      around 80-100% of melanocytes were positive for CPDs in tan, intermediate and
      light skin types. In contrast, in dark and brown skin types, CPDs were found in
      only approximately 15% of melanocytes at the highest dose. CONCLUSIONS: This work
      demonstrates that melanocytes from constitutively highly pigmented skin types are
      less impacted in terms of UVR-induced DNA damage than those from lighter skin
      types, even those that are moderately pigmented.

PMID- 23550735
TI  - A severe case of haemodynamic instability during anidulafungin administration.
AB  - WHAT IS KNOWN AND OBJECTIVE: Anidulafugin is an echinocandin used for the
      treatment of candida infections in non-neutropenic adults. Echinocandins show few
      drug-drug interactions and are usually well tolerated. We report a case of acute
      hypotension, bradycardia and haemodynamic instability with consecutive
      cardiopulmonary resuscitation during anidulafungin administration. CASE SUMMARY:
      A 41-year-old man ICU patient received anidulafungin for a suspected Candida
      glabrata infection. During the first administration of the drug, he developed
      acute haemodynamic instability with hypotension and bradycardia. The infusion was
      discontinued immediately and cardiopulmonary resuscitation was performed
      successfully. The patient regained haemodynamic stability. WHAT IS NEW AND
      CONCLUSION: To the authors' knowledge, this is the first report of a life
      threatening adverse event due to haemodynamic instability during anidulafungin
      administration. Cardiac toxicity associated with echinocandins has been
      described. Further studies seem to be mandatory to investigate this potential
      risk.

PMID- 23550736
TI  - Activation of UbcH5c~Ub is the result of a shift in interdomain motions of the
      conjugate bound to U-box E3 ligase E4B.
AB  - Post-translational modification of proteins with ubiquitin is mediated by dynamic
      multienzyme machinery (E1, E2, and E3). E3 ubiquitin ligases play a key role
      acting as both scaffolds to bring reactants together and activators to catalyze
      ubiquitin (Ub) transfer from E2~Ub conjugates to substrates. Our recent studies
      provided insights into the mechanism of the activation event; binding of an E3 to
      an E2~Ub conjugate was found to affect the motions of E2~Ub and allosterically
      stimulate Ub transfer. This proposed mechanism implies that the dynamics of the
      conjugate, which has been shown to occupy a wide range of E2~Ub orientations,
      will be altered significantly upon binding of E3. To directly assess the effect
      of E3 binding on E2~Ub dynamics, we undertook an in-depth comparative analysis of
      (15)N nuclear magnetic resonance relaxation of UbcH5c~Ub in the absence and
      presence of the E3 ligase, E4B. Challenges encountered in deciphering interdomain
      motions for this ternary complex are discussed along with the limitations of the
      current approaches. Notably, although a reduction in interdomain dynamics of
      UbcH5c~Ub is observed upon binding to E4B, Ub retains an extensive degree of
      flexibility. These results provide strong support for our dynamic model of a
      significant orientational bias of Ub toward a more closed conformation in the
      E3/E2~Ub complex.

PMID- 23550737
TI  - Is the non-verbal behavioural emotion-processing profile of bipolar disorder
      impaired? A critical review.
AB  - OBJECTIVE: Growing evidence suggests that patients with bipolar disorder (BD) are
      impaired in their ability to process non-verbal emotion, although few
      comprehensive reviews of the behavioural literature exist, and there has been
      little consideration of methodological issues that may account for discrepant
      empirical findings. This review examines the behavioural facial, prosodic and
      multimodal processing literature in BD and discusses methodological issues in the
      context of this evidence. METHOD: Major computer databases including Google
      Scholar and PsychINFO were consulted to conduct a comprehensive review of
      quantitative behavioural differences in the emotion-processing literature in BD.
      Articles were accepted only if the target population sample met criteria for a
      DSM-III, DSM-IV or ICD-10 diagnosis, and they contained a healthy control group.
      RESULTS: The current literature suggests that facial emotion processing is
      impaired, and there is preliminary evidence for some behavioural impairment in
      the processing of emotional prosody. CONCLUSION: The specificity or
      generalisability of impairments in facial emotion processing and the effects of
      mood state are unclear. Similarly, the lack of clarity around the impact of
      auditory processes on emotional prosody processing warrants a comprehensive
      examination of the auditory profile in BD.

PMID- 23550739
TI  - New investigational drugs for androgenetic alopecia.
AB  - INTRODUCTION: Androgenetic alopecia (AGA) is the most common form of hair loss,
      however current treatment options are limited and moderately effective. In the
      past few years, there has been an increased interest in deciphering the molecular
      mechanisms responsible for this disorder, which has opened the possibility of
      novel treatments that promise to not only stimulate hair growth, but also to
      induce formation of new hair follicles. AREAS COVERED: The future holds more
      effective topical treatments with less systemic side effects (such as topical 5
      alfa-reductase inhibitors), prostaglandin analogs and antagonists, medications
      which act through the Wnt signaling pathway, stem cells for hair regeneration,
      platelet-rich plasma (PRP) and more effective ways of transplanting hair. A
      comprehensive search was made using PubMed, GoogleScholar and Clinicaltrial.gov
      using different combination of key words, which included AGA treatment, new
      treatments for AGA, Wnt pathway, prostaglandins, PRP and stem cells for hair
      regrowth. EXPERT OPINION: In the near future, treatments with topical 5-alfa
      reductase inhibitors and prostaglandin agonists or antagonists are expected. More
      evidence is needed to verify the efficacy of PRP. Although hair follicle
      bioengineering and multiplication is a fascinating and promising field, it is
      still a long way from being available to clinicians.

PMID- 23550738
TI  - Chronic ethanol (EtOH) consumption differentially alters gray and white matter
      EtOH methyl 1H magnetic resonance intensity in the primate brain.
AB  - BACKGROUND: In vivo magnetic resonance spectroscopy (MRS) has previously been
      used to directly monitor brain ethanol (EtOH). It has been proposed that the EtOH
      methyl 1H resonance intensity is larger in EtOH-tolerant individuals than in
      sensitive individuals. To characterize the relationship between long-term EtOH
      exposure and the brain EtOH MRS intensity, we present data from a longitudinal
      experiment conducted using nonhuman primate subjects. METHODS: In vivo MRS was
      used to measure the gray matter (GM) and white matter (WM) EtOH methyl 1H MRS
      intensity in 18 adult male rhesus macaques at 4 time points throughout the course
      of a chronic drinking experiment. Time points were prior to EtOH drinking,
      following a 3-month EtOH induction procedure, and following 6, and 12 subsequent
      months of 22 h/d of "open access" to EtOH (4% w/v) and water. RESULTS: The EtOH
      methyl 1H MRS intensity, which we observed to be independent of age over the
      range examined, increased with chronic EtOH exposure in GM and WM. In GM, MRS
      intensity increased from naive level following the EtOH induction period (90 g/kg
      cumulative EtOH intake). In WM, MRS intensity was not significantly different
      from the EtOH-naive state until after 6 months of 22-hour free access (110 to 850
      g/kg cumulative intake range). The WM MRS intensity in the EtOH-naive state was
      positively correlated with future drinking, and the increase in WM MRS intensity
      was negatively correlated with the amount of EtOH consumed throughout the
      experiment. CONCLUSIONS: Chronic exposure to EtOH is associated with brain
      changes that result in differential increases in EtOH MRS intensity in GM and WM.
      The EtOH-naive WM MRS intensity pattern is consistent with its previously
      proposed relationship to innate tolerance to the intoxicating effects of EtOH.
      EtOH-dependent MRS intensity changes in GM required less EtOH exposure than was
      necessary to produce changes in WM. Within WM, an unexpected, potentially age
      dependent, enhanced sensitivity to EtOH in light drinkers relative to heavy
      drinkers was observed.

PMID- 23550740
TI  - Multicenter randomized prospective clinical evaluation of meloxicam administered
      via transmucosal oral spray in client-owned dogs.
AB  - The clinical safety and efficacy of a transmucosal oral spray (TMOS) formulation
      of meloxicam was evaluated for the control of pain and inflammation associated
      with osteoarthritis in dogs. A total of 280 client-owned dogs were enrolled at
      fourteen veterinary clinics: there were 187 dogs in the meloxicam TMOS group and
      93 in the placebo control group. Dogs received placebo or treatment spray once
      daily for twenty-eight days. Improvement in signs of osteoarthritis was measured
      using client-specific outcome measures (CSOM) made at days 14 and 28 and
      veterinary assessments of lameness and pain on palpation made at day 28. A
      significantly higher number of dogs in the meloxicam TMOS group were treatment
      successes at 28 days (72.6%) compared with the placebo group (46.9%), based on
      CSOM scores. Total CSOM scores were significantly lower in the meloxicam TMOS
      treated group compared with the placebo group at both 14 and 28 days. Differences
      between treatment groups were not observed in veterinary assessments.
      Gastrointestinal effects of meloxicam were observed in some animals. Meloxicam
      TMOS was found to be safe and effective in dogs for the control of pain and
      inflammation associated with osteoarthritis. 

PMID- 23550741
TI  - Medication use among Australian adults with intellectual disability in primary
      healthcare settings: a cross-sectional study.
AB  - BACKGROUND: There is concern about widespread medication use by people with
      intellectual disability (ID), especially psychotropic and anticonvulsant agents.
      However, there is sparse information on prescribing patterns in Australia.
      METHOD: This cross-sectional study was conducted between 2000 and 2002 among
      adults with ID who live in the community in Brisbane, Australia. Medication data
      were extracted from a health screening tool. Demographic and medical data were
      collected from telephone interviews and medical records. RESULTS: Of 117
      participants, 35% were prescribed psychotropic medications, most commonly
      antipsychotics, and 26% anticonvulsants. Complementary medications (vitamins,
      minerals, amino acids, fish oil, and herbal products) were used by 29% of
      participants. After adjusting for potentially confounding variables, psychotropic
      medication use was significantly associated with having a psychiatric illness
      (adjusted odds ratio = 4.6, 95% CI [1.0, 20.6]) and challenging behaviours (4.4,
      [1.1, 17.3]). CONCLUSIONS: People with ID use a broad range of medications.
      Psychotropic medications continue to be the most predominant agents prescribed
      for this population. Psychotropic medication use is positively associated with
      having a psychiatric illness and challenging behaviours.

PMID- 23550742
TI  - High incidence of post-injury pneumonia in intensive care-treated trauma
      patients.
AB  - INTRODUCTION: Trauma patients are susceptible to post-injury infections. We
      investigated the incidence, as well as risk factors for development of pneumonia
      in intensive care unit (ICU)-treated trauma patients. In addition, we report
      pathogens identified in patients that developed pneumonia. METHODS: The study
      cohort consisted of 322 trauma patients admitted to the ICU at a level-one trauma
      centre following initial resuscitation. Patients 15 years or older with an ICU
      stay of more than 24 h were included. We investigated pre-hospital and hospital
      parameters during the first 24 h after admission and their possible association
      with pneumonia within 10 days of ICU admission. RESULTS: Majority of the patients
      were male (78%) and the median age was 41 years. The overall degree of injury was
      high with a median Injury Severity Score (ISS) of 24. Overall 30-day mortality
      was 9%. Eighty-five (26%) patients developed pneumonia during their first 10 days
      in the ICU. Univariate logistic regression revealed that intubation in the field,
      shock, Glasgow Coma Scale (GCS) 3-8, major surgery within 24 h after admission,
      massive transfusion and ISS > 24 were all risk factors for subsequent development
      of pneumonia. In the multivariable model, only GCS 3-8 was identified as an
      independent risk factor. In 42 out of the 85 cases of pneumonia, the diagnosis
      was defined by significant growth of at least one pathogen where
      Enterobacteriaceae and Staphylococcus aureus were the most common. CONCLUSIONS:
      Pneumonia is a common complication among ICU-treated trauma patients. Reduced
      consciousness is an independent risk factor for development of pneumonia after
      severe injury.

PMID- 23550743
TI  - Graphene--nanotube--iron hierarchical nanostructure as lithium ion battery anode.
AB  - In this study, we report a novel route via microwave irradiation to synthesize a
      bio-inspired hierarchical graphene--nanotube--iron three-dimensional
      nanostructure as an anode material in lithium-ion batteries. The nanostructure
      comprises vertically aligned carbon nanotubes grown directly on graphene sheets
      along with shorter branches of carbon nanotubes stemming out from both the
      graphene sheets and the vertically aligned carbon nanotubes. This bio-inspired
      hierarchical structure provides a three-dimensional conductive network for
      efficient charge-transfer and prevents the agglomeration and restacking of the
      graphene sheets enabling Li-ions to have greater access to the electrode
      material. In addition, functional iron-oxide nanoparticles decorated within the
      three-dimensional hierarchical structure provides outstanding lithium storage
      characteristics, resulting in very high specific capacities. The anode material
      delivers a reversible capacity of ~1024 mA . h . g(-1) even after prolonged
      cycling along with a Coulombic efficiency in excess of 99%, which reflects the
      ability of the hierarchical network to prevent agglomeration of the iron-oxide
      nanoparticles.

PMID- 23550745
TI  - Parasite co-transmission and the evolutionary epidemiology of virulence.
AB  - Hosts are often co-infected by several parasite genotypes of the same species or
      even by different species and this is known to affect virulence evolution.
      However, epidemiological models typically assume that only one of the co
      infecting strains can be transmitted at the same time, which is often at odds
      with the observed biology. Here, I study the effect of co-transmission on
      virulence evolution in a case where parasites compete for host resources. For co
      infections by strains of the same species, increased co-transmission selects for
      less virulent strains. This is because co-transmission aligns the interests of co
      infecting strains, thus decreasing the selective pressure for increased within
      host competitiveness. For co-infection caused by different parasite species, the
      evolutionary outcome depends on the respective virulence of the two parasite
      species. Finally, I investigate asymmetric scenarios, for example that of plant
      viruses that require "helper" molecules produced by viruses from another species
      to be transmitted. These results show that even if parasite strains compete for
      host resources, the prevalence of co-infections can be a poor predictor of
      virulence evolution.

PMID- 23550744
TI  - Commentary: The observed association between autistic severity measured by the
      social responsiveness scale (SRS) and general psychopathology--a response to Hus
      et al.(2013).

PMID- 23550746
TI  - Infectious adaptation: potential host range of a defensive endosymbiont in
      Drosophila.
AB  - Maternally transmitted symbionts persist over macroevolutionary timescales by
      undergoing occasional lateral transfer to new host species. To invade a new
      species, a symbiont must survive and reproduce in the new host, undergo maternal
      transmission, and confer a selective benefit sufficient to overcome losses due to
      imperfect maternal transmission. Drosophila neotestacea is naturally infected
      with a strain of Spiroplasma that restores fertility to nematode-parasitized
      females, which are otherwise sterilized by parasitism. We experimentally
      transferred Spiroplasma from D. neotestacea to four other species of mycophagous
      Drosophila that vary in their ability to resist and/or tolerate nematode
      parasitism. In all four species, Spiroplasma achieved within-host densities and
      experienced rates of maternal transmission similar to that in D. neotestacea.
      Spiroplasma restored fertility to nematode-parasitized females in one of these
      novel host species. Based on estimates of maternal transmission fidelity and the
      expected benefit of Spiroplasma infection in the wild, we conclude that
      Spiroplasma has the potential to spread and become abundant within Drosophila
      putrida, which is broadly sympatric with D. neotestacea and in which females are
      rendered completely sterile by nematode parasitism. Thus, a major adaptation
      within D. putrida could arise via lateral transmission of a heritable symbiont
      from D. neotestacea.

PMID- 23550747
TI  - Reproductive isolation and local adaptation quantified for a chromosome inversion
      in a malaria mosquito.
AB  - Chromosome inversions have long been thought to be involved in speciation and
      local adaptation. We have little quantitative information, however, about the
      effects that inversion polymorphisms have on reproductive isolation and
      viability. Here we provide the first estimates from any organism for the total
      amount of reproductive isolation associated with an inversion segregating in
      natural populations. We sampled chromosomes from 751 mosquitoes of the malaria
      vector Anopheles funestus along a 1421 km transect in Cameroon that traverses
      savannah, highland, and rainforest ecological zones. We then developed a series
      of population genetic models that account for selection, migration, and
      assortative mating, and fit the models to the data using likelihood. Results from
      the best-fit models suggest there is strong local adaptation, with relative
      viabilities of homozygotes ranging from 25% to 130% compared to heterozygotes.
      Viabilities vary qualitatively between regions: the inversion is underdominant in
      the savannah, whereas in the highlands it is overdominant. The inversion is also
      implicated in strong assortative mating. In the savannah, the two homozygote
      forms show 92% reproductive isolation, suggesting that this one inversion can
      generate most of the genetic barriers needed for speciation.

PMID- 23550748
TI  - Avian brood parasitism and ectoparasite richness-scale-dependent diversity
      interactions in a three-level host-parasite system.
AB  - Brood parasitic birds, their foster species and their ectoparasites form a
      complex coevolving system composed of three hierarchical levels. However, effects
      of hosts' brood parasitic life-style on the evolution of their louse
      (Phthiraptera: Amblycera, Ischnocera) lineages have never been tested. We present
      two phylogenetic analyses of ectoparasite richness of brood parasitic clades. Our
      hypothesis was that brood parasitic life-style affects louse richness negatively
      across all avian clades due to the lack of vertical transmission routes. Then,
      narrowing our scope to brood parasitic cuckoos, we explored macroevolutionary
      factors responsible for the variability of their louse richness. Our results show
      that taxonomic richness of lice is lower on brood parasitic clades than on their
      nonparasitic sister clades. However, we found a positive covariation between the
      richness of cuckoos' Ischnoceran lice and the number of their foster species,
      possibly due to the complex and dynamic subpopulation structure of cuckoo species
      that utilize several host species. We documented diversity interactions across a
      three-level host parasite system and we found evidence that brood parasitism has
      opposing effects on louse richness at two slightly differing macroevolutionary
      scales, namely the species richness and the genera richness.

PMID- 23550749
TI  - Stochastic temperatures impede RNA virus adaptation.
AB  - Constant environments are often assumed to favor the evolution of specialization
      whereas exposure to changing environments may favor the evolution of generalists.
      Here we explored the phenotypic and molecular changes associated with evolving an
      RNA virus in constant versus fluctuating temperature environments. We used
      vesicular stomatitis virus (VSV) to determine whether selection at a constant
      temperature entails a performance trade-off at an unselected temperature, whether
      virus populations evolve to be generalists when selected in deterministically
      changing temperature environments, and whether selection under stochastically
      changing temperatures prevents evolved generalization, such as by constraining
      the ability for viruses to adaptively improve. We observed that all VSV lineages
      evolved at constant temperatures showed fitness gains in their selected
      temperature with little evidence for trade-offs in performance in the unselected
      environment. Evolution in deterministically and stochastically changing
      temperatures led to populations with the highest and lowest overall fitness
      gains, respectively. Sequence analysis revealed little evidence for convergent
      molecular evolution among lineages within the same treatment. Across all
      temperature treatments, the majority of genome substitutions occurred in the G
      (glycoprotein) gene, suggesting that this locus for the cell-binding protein
      plays a key role in dictating VSV performance under changing temperature.

PMID- 23550750
TI  - A simple model explains the dynamics of preferential host switching among mammal
      RNA viruses.
AB  - A growing number of studies support a tendency toward preferential host
      switching, by parasites and pathogens, over relatively short phylogenetic
      distances. This suggests that a host switch is more probable if a potential host
      is closely related to the original host than if it is a more distant relative.
      However, despite its importance for the health of humans, livestock, and
      wildlife, the detailed dynamics of preferential host switching have, so far, been
      little studied. We present an empirical test of two theoretical models of
      preferential host switching, using observed phylogenetic distributions of host
      species for RNA viruses of three mammal orders (primates, carnivores, and
      ungulates). The analysis focuses on multihost RNA virus species, because their
      presence on multiple hosts and their estimated ages of origin indicate recent
      host switching. Approximate Bayesian computation was used to compare observed
      phylogenetic distances between hosts with those simulated under the theoretical
      models. The results support a decreasing sigmoidal model of preferential host
      switching, with a strong effect from increasing phylogenetic distance, on all
      three studied host phylogenies. This suggests that the dynamics of host switching
      are fundamentally similar for RNA viruses of different mammal orders and,
      potentially, a wider range of coevolutionary systems.

PMID- 23550751
TI  - Evidence for climate-driven diversification? A caution for interpreting ABC
      inferences of simultaneous historical events.
AB  - Approximate Bayesian computation (ABC) is rapidly gaining popularity in
      population genetics. One example, msBayes, infers the distribution of divergence
      times among pairs of taxa, allowing phylogeographers to test hypotheses about
      historical causes of diversification in co-distributed groups of organisms. Using
      msBayes, we infer the distribution of divergence times among 22 pairs of
      populations of vertebrates distributed across the Philippine Archipelago. Our
      objective was to test whether sea-level oscillations during the Pleistocene
      caused diversification across the islands. To guide interpretation of our
      results, we perform a suite of simulation-based power analyses. Our empirical
      results strongly support a recent simultaneous divergence event for all 22 taxon
      pairs, consistent with the prediction of the Pleistocene-driven diversification
      hypothesis. However, our empirical estimates are sensitive to changes in prior
      distributions, and our simulations reveal low power of the method to detect
      random variation in divergence times and bias toward supporting clustered
      divergences. Our results demonstrate that analyses exploring power and prior
      sensitivity should accompany ABC model selection inferences. The problems we
      identify are potentially mitigable with uniform priors over divergence models
      (rather than classes of models) and more flexible prior distributions on
      demographic and divergence-time parameters.

PMID- 23550752
TI  - Effects of climatic and geological processes during the pleistocene on the
      evolutionary history of the northern cavefish, Amblyopsis spelaea (teleostei:
      amblyopsidae).
AB  - Climatic and geological processes associated with glaciation cycles during the
      Pleistocene have been implicated in influencing patterns of genetic variation and
      promoting speciation of temperate flora and fauna. However, determining the
      factors promoting divergence and speciation is often difficult in many groups
      because of our limited understanding of potential vicariant barriers and
      connectivity between populations. Pleistocene glacial cycles are thought to have
      significantly influenced the distribution and diversity of subterranean
      invertebrates; however, impacts on subterranean aquatic vertebrates are less
      clear. We employed several hypothesis-driven approaches to assess the impacts of
      Pleistocene climatic and geological changes on the Northern Cavefish, Amblyopsis
      spelaea, whose current distribution occurs near the southern extent of glacial
      advances in North America. Our results show that the modern Ohio River has been a
      significant barrier to dispersal and is correlated with patterns of genetic
      divergence. We infer that populations were isolated in two refugia located north
      and south of the Ohio River during the most recent two glacial cycles with
      evidence of demographic expansion in the northern isolate. Finally, we conclude
      that climatic and geological processes have resulted in the formation of cryptic
      forms and advocate recognition of two distinct phylogenetic lineages currently
      recognized as A. spelaea.

PMID- 23550753
TI  - Isoprene synthase genes form a monophyletic clade of acyclic terpene synthases in
      the TPS-B terpene synthase family.
AB  - Many plants emit significant amounts of isoprene, which is hypothesized to help
      leaves tolerate short episodes of high temperature. Isoprene emission is found in
      all major groups of land plants including mosses, ferns, gymnosperms, and
      angiosperms; however, within these groups isoprene emission is variable. The
      patchy distribution of isoprene emission implies an evolutionary pattern
      characterized by many origins or many losses. To better understand the evolution
      of isoprene emission, we examine the phylogenetic relationships among isoprene
      synthase and monoterpene synthase genes in the angiosperms. In this study we
      identify nine new isoprene synthases within the rosid angiosperms. We also
      document the capacity of a myrcene synthase in Humulus lupulus to produce
      isoprene. Isoprene synthases and (E)-beta-ocimene synthases form a monophyletic
      group within the Tps-b clade of terpene synthases. No asterid genes fall within
      this clade. The chemistry of isoprene synthase and ocimene synthase is similar
      and likely affects the apparent relationships among Tps-b enzymes. The chronology
      of rosid evolution suggests a Cretaceous origin followed by many losses of
      isoprene synthase over the course of evolutionary history. The phylogenetic
      pattern of Tps-b genes indicates that isoprene emission from non-rosid
      angiosperms likely arose independently.

PMID- 23550754
TI  - Origin and diversification of the California flora: re-examining classic
      hypotheses with molecular phylogenies.
AB  - The California Floristic Province exhibits one of the richest floras on the
      planet, with more than 5500 native plant species, approximately 40% of which are
      endemic. Despite its impressive diversity and the attention it has garnered from
      ecologists and evolutionary biologists, historical causes of species richness and
      endemism in California remain poorly understood. Using a phylogenetic analysis of
      16 angiosperm clades, each containing California natives in addition to species
      found only outside California, we show that CA's current biodiversity primarily
      results from low extinction rates, as opposed to elevated speciation or
      immigration rates. Speciation rates in California were lowest among Arcto
      Tertiary lineages (i.e., those colonizing California from the north, during the
      Tertiary), but extinction rates were universally low across California native
      plants of all historical, geographic origins. In contrast to long-accepted ideas,
      we find that California diversification rates were generally unaffected by the
      onset of the Mediterranean climate. However, the Mediterranean climate coincided
      with immigration of many desert species, validating one previous hypothesis
      regarding origins of CA's plant diversity. This study implicates topographic
      complexity and climatic buffering as key, long-standing features of CA's
      landscape favoring plant species persistence and diversification, and highlights
      California as an important refuge under changing climates.

PMID- 23550755
TI  - Hybrid speciation and independent evolution in lineages of alpine butterflies.
AB  - The power of hybridization between species to generate variation and fuel
      adaptation is poorly understood despite long-standing interest. There is,
      however, increasing evidence that hybridization often generates biodiversity,
      including via hybrid speciation. We tested the hypothesis of hybrid speciation in
      butterflies occupying extreme, high-altitude habitats in four mountain ranges in
      western North America with an explicit, probabilistic model, and genome-wide DNA
      sequence data. Using this approach, in concert with ecological experiments and
      observations and morphological data, we document three lineages of hybrid origin.
      These lineages have different genome admixture proportions and distinctive trait
      combinations that suggest unique and independent evolutionary histories.

PMID- 23550756
TI  - Deciphering the evolutionary history and developmental mechanisms of a complex
      sexual ornament: the abdominal appendages of Sepsidae (Diptera).
AB  - Male abdomen appendages are a novel trait found within Sepsidae (Diptera). Here
      we demonstrate that they are likely to have evolved once, were lost three times,
      and then secondarily gained in one lineage. The developmental basis of these
      appendages was investigated by counting the number of histoblast cells in each
      abdominal segment in four species: two that represented the initial instance of
      appendage evolution, one that has secondarily gained appendages, and one species
      that did not have appendages. Males of all species with appendages have elevated
      cell counts for the fourth segment, which gives rise to the appendages. In
      Perochaeta dikowi, which reacquired the trait, the females also have elevated
      cell count on the fourth segment despite the fact that females do not develop
      appendages. The species without appendages has similar cell counts in all
      segments regardless of sex. These results suggest that the basis for appendage
      development is shared in males across all species, but the sexual dimorphism is
      regulated differently in P. dikowi.

PMID- 23550758
TI  - Evolution of transcription networks in response to temporal fluctuations.
AB  - Organisms respond to changes in their environment over a wide range of biological
      and temporal scales. Such phenotypic plasticity can involve developmental,
      behavioral, physiological, and genetic shifts. The adaptive value of a plastic
      response is known to depend on the nature of the information that is available to
      the organism as well as the direct and indirect costs of the plastic response. We
      modeled the dynamic process of simple gene regulatory networks as they responded
      to temporal fluctuations in environmental conditions. We simulated the evolution
      of networks to determine when genes that function solely as transcription
      factors, with no direct function of their own, are beneficial to the function of
      the network. When there is perfect information about the environment and there is
      no timing information to be extracted then there is no advantage to adding pure
      transcription factor genes to the network. In contrast, when there is either
      timing information that can be extracted or only indirect information about the
      current state of the environment then additional transcription factor genes
      improve the evolved network fitness.

PMID- 23550757
TI  - Recurrent and recent selective sweeps in the piRNA pathway.
AB  - Uncontrolled transposable element (TE) insertions and excisions can cause
      chromosome breaks and mutations with dramatic deleterious effects. The PIWI
      interacting RNA (piRNA) pathway functions as an adaptive TE silencing system
      during germline development. Several essential piRNA pathway proteins appear to
      be rapidly evolving, suggesting that TEs and the silencing machinery may be
      engaged in a classical "evolutionary arms race." Using a variety of molecular
      evolutionary and population genetic approaches, we find that the piRNA pathway
      genes rhino, krimper, and aubergine show patterns suggestive of extensive
      recurrent positive selection across Drosophila species. We speculate that
      selection on these proteins reflects crucial roles in silencing unfamiliar
      elements during vertical and horizontal transmission of TEs into naive
      populations and species, respectively.

PMID- 23550759
TI  - Genetic variation in HIF signaling underlies quantitative variation in
      physiological and life-history traits within lowland butterfly populations.
AB  - Oxygen conductance to the tissues determines aerobic metabolic performance in
      most eukaryotes but has cost/benefit tradeoffs. Here we examine in lowland
      populations of a butterfly a genetic polymorphism affecting oxygen conductance
      via the hypoxia-inducible factor (HIF) pathway, which senses intracellular oxygen
      and controls the development of oxygen delivery networks. Genetically distinct
      clades of Glanville fritillary (Melitaea cinxia) across a continental scale
      maintain, at intermediate frequencies, alleles in a metabolic enzyme (succinate
      dehydrogenase, SDH) that regulates HIF-1alpha. One Sdhd allele was associated
      with reduced SDH activity rate, twofold greater cross-sectional area of
      tracheoles in flight muscle, and better flight performance. Butterflies with less
      tracheal development had greater post-flight hypoxia signaling, swollen &
      disrupted mitochondria, and accelerated aging of flight metabolic performance.
      Allelic associations with metabolic and aging phenotypes were replicated in
      samples from different clades. Experimentally elevated succinate in pupae
      increased the abundance of HIF-1alpha and expression of genes responsive to HIF
      activation, including tracheal morphogenesis genes. These results indicate that
      the hypoxia inducible pathway, even in lowland populations, can be an important
      axis for genetic variation underlying intraspecific differences in oxygen
      delivery, physiological performance, and life history.

PMID- 23550760
TI  - Properties of spontaneous mutational variance and covariance for wing size and
      shape in Drosophila melanogaster.
AB  - We estimated mutational variance-covariance matrices, M, for wing shape and size
      in two genotypes of Drosophila melanogaster after 192 generations of mutation
      accumulation. We characterized 21 potentially independent aspects of wing shape
      and size using geometric morphometrics, and analyzed the data using a likelihood
      based factor-analytic approach. We implement a previously unused analysis that
      describes those directions with the greatest difference in evolvability between
      pairs of matrices. There are significant mutational effects on 19 of 21 possible
      aspects of wing form, consistent with the high dimensionality of standing genetic
      variation for wing shape previously identified in D. melanogaster. Mutations have
      partially recessive effects, consistent with average dominance around 0.25. Sex
      specific matrices are relatively similar, although male-specific matrices are
      slightly larger, as expected due to dosage compensation on the X chromosome.
      Genotype-specific matrices are quite different. Matrices may differ both because
      of sampling error based on small samples of mutations with large phenotypic
      effects, and because of the mutational properties of the genotypes. Genotypic
      differences are likely to be involved, as the two genotypes have different
      molecular mutation rates and properties.

PMID- 23550761
TI  - Joint allelic effects on fitness and metric traits.
AB  - Theoretical explanations of empirically observed standing genetic variation,
      mutation, and selection suggest that many alleles must jointly affect fitness and
      metric traits. However, there are few direct demonstrations of the nature and
      extent of these pleiotropic associations. We implemented a mutation accumulation
      (MA) divergence experimental design in Drosophila serrata to segregate genetic
      variants for fitness and metric traits. By exploiting naturally occurring MA line
      extinctions as a measure of line-level total fitness, manipulating sexual
      selection, and measuring productivity we were able to demonstrate genetic
      covariance between fitness and standard metric traits, wing size, and shape.
      Larger size was associated with lower total fitness and male sexual fitness, but
      higher productivity. Multivariate wing shape traits, capturing major axes of wing
      shape variation among MA lines, evolved only in the absence of sexual selection,
      and to the greatest extent in lines that went extinct, indicating that mutations
      contributing wing shape variation also typically had deleterious effects on both
      total fitness and male sexual fitness. This pleiotropic covariance of metric
      traits with fitness will drive their evolution, and generate the appearance of
      selection on the metric traits even in the absence of a direct contribution to
      fitness.

PMID- 23550762
TI  - Fixation of mutators in asexual populations: the role of genetic drift and
      epistasis.
AB  - We study the evolutionary dynamics of an asexual population of nonmutators and
      mutators on a class of epistatic fitness landscapes. We consider the situation in
      which all mutations are deleterious and mutators are produced from nonmutators
      continually at a constant rate. We find that in an infinitely large population, a
      minimum nonmutator-to-mutator conversion rate is required to fix the mutators but
      an arbitrarily small conversion rate results in the fixation of mutators in a
      finite population. We calculate analytical expressions for the mutator fraction
      at mutation-selection balance and fixation time for mutators in a finite
      population when the difference between the mutation rate for mutator and
      nonmutator is smaller (regime I) and larger (regime II) than the selection
      coefficient. Our main result is that in regime I, the mutator fraction and the
      fixation time are independent of epistasis but in regime II, mutators are rarer
      and take longer to fix when the decrease in fitness with the number of
      deleterious mutations occurs at an accelerating rate (synergistic epistasis) than
      at a diminishing rate (antagonistic epistasis). Our analytical results are
      compared with numerics and their implications are discussed.

PMID- 23550764
TI  - Bidirectional shifts in colony queen number in a socially polymorphic ant
      population.
AB  - The breeding system of social organisms affects many important aspects of social
      life. Some species vary greatly in the number of breeders per group, but the
      mechanisms and selective pressures contributing to the maintenance of this
      polymorphism in social structure remain poorly understood. Here, we take
      advantage of a genetic dataset that spans 15 years to investigate the dynamics of
      colony queen number within a socially polymorphic ant species. Our study
      population of Formica selysi has single- and multiple-queen colonies. We found
      that the social structure of this species is somewhat flexible: on average, each
      year 3.2% of the single-queen colonies became polygynous, and conversely 1.4% of
      the multiple-queen colonies became monogynous. The annualized queen replacement
      rates were 10.3% and 11.9% for single- and multiple-queen colonies, respectively.
      New queens were often but not always related to previous colony members. At the
      population level, the social polymorphism appeared stable. There was no genetic
      differentiation between single- and multiple-queen colonies at eight
      microsatellite loci, suggesting ongoing gene flow between social forms. Overall,
      the regular and bidirectional changes in queen number indicate that social
      structure is a labile trait in F. selysi, with neither form being favored within
      a time-frame of 15 years.

PMID- 23550763
TI  - An evaluation of the hybrid speciation hypothesis for Xiphophorus clemenciae
      based on whole genome sequences.
AB  - Once thought rare in animal taxa, hybridization has been increasingly recognized
      as an important and common force in animal evolution. In the past decade, a
      number of studies have suggested that hybridization has driven speciation in some
      animal groups. We investigate the signature of hybridization in the genome of a
      putative hybrid species, Xiphophorus clemenciae, through whole genome sequencing
      of this species and its hypothesized progenitors. Based on analysis of this data,
      we find that X. clemenciae is unlikely to have been derived from admixture
      between its proposed parental species. However, we find significant evidence for
      recent gene flow between Xiphophorus species. Although we detect genetic exchange
      in two pairs of species analyzed, the proportion of genomic regions that can be
      attributed to hybrid origin is small, suggesting that strong behavioral premating
      isolation prevents frequent hybridization in Xiphophorus. The direction of gene
      flow between species is potentially consistent with a role for sexual selection
      in mediating hybridization.

PMID- 23550765
TI  - The design of a beautiful weapon: compensation for opposing sexual selection on a
      trait with two functions.
AB  - Male fiddler crabs, genus Uca, have one greatly enlarged claw with which they
      court females and threaten and fight other males. Longer claws are more effective
      signals but are thought to be less effective weapons because the relative closing
      force at the tip of the claw decreases with claw length. We studied claw
      morphology and fighting in Uca terpsichores and Uca beebei and found a mechanism
      that may resolve opposing selection for signaling and fighting ability. When
      males fought they delivered gripping forces not at the tips but at the tubercles
      on the inner margins of their claws' fingers. As claws grow, these tubercles
      remain relatively close to the apex of the gape. Consequently, the mechanical
      advantage that governs the forces that can be delivered at these tubercles
      decreases only slightly with increasing claw length allowing the claw to be an
      effective signal and a powerful weapon. Animal weapons are exceptionally diverse
      in form and detail of armature and the causes of this diversity are poorly
      understood. We suggest that the designs of weapons may often reflect compensatory
      patterns of growth and placement of armature that enhances the weapon's overall
      utility for multiple uses in competition for mates.

PMID- 23550766
TI  - Male-biased fitness effects of spontaneous mutations in Drosophila melanogaster.
AB  - In populations with males and females, sexual selection may often represent a
      major component of overall selection. Sexual selection could act to eliminate
      deleterious alleles in concert with other forms of selection, thereby improving
      the fitness of sexual populations. Alternatively, the divergent reproductive
      strategies of the sexes could promote the maintenance of sexually antagonistic
      variation, causing sexual populations to be less fit. The net impact of sexual
      selection on fitness is not well understood, due in part to limited data on the
      sex-specific effects of spontaneous mutations on total fitness. Using a set of
      mutation accumulation lines of Drosophila melanogaster, we found that mutations
      were deleterious in both sexes and had larger effects on fitness in males than in
      females. This pattern is expected to reduce the mutation load of sexual females
      and promote the maintenance of sexual reproduction.

PMID- 23550768
TI  - Convergent evolution as a generator of phenotypic diversity in threespine
      stickleback.
AB  - Convergent evolution, in which populations produce similar phenotypes in response
      to similar selection pressure, is strong evidence for the role of natural
      selection in shaping biological diversity. In some cases, closely related
      populations can produce functionally similar but phenotypically divergence forms
      in response to selection. Functional convergence with morphological divergence
      has been observed in laboratory selection experiments and computer simulations,
      but while potentially common, is rarely recognized in nature. Here, we present
      data from the North Pacific threespine stickleback radiation showing that
      ecologically and functionally similar, but morphologically divergent phenotypes
      rapidly evolved when an ancestral population colonized freshwater benthic
      habitats in parallel. In addition, we show that in this system, functional
      convergence substantially increases morphospace occupation relative to ancestral
      phenotypes, which suggests that convergent evolution may, paradoxically, be an
      important and previously underappreciated source of morphological diversity.

PMID- 23550767
TI  - Floral paedomorphy leads to secondary specialization in pollination of Madagascar
      Dalechampia (Euphorbiaceae).
AB  - The traditional evolutionary interpretation of Von Baer's "laws" of embryology is
      that retention of early developmental forms into adulthood (paedomorphosis) leads
      to the evolution of simpler or more generalized morphology and ecology. Here we
      show that paedomorphosis can also be involved in an increase in ecological
      specialization, in this case of plant-pollinator relationships. A paedomorphic
      transition from generalized pollination (by several functional types of
      pollinators) to specialized pollination (by one or a few species in one
      functional type) occurred in a clade of endemic Madagascar vines (Dalechampia
      spp., Euphorbiaceae). This evolutionary transition involved staminate flowers
      that fail to develop "normally," instead holding mature pollen inside virtually
      unopened, bud-like flowers. This paedomorphic morphology restricts reward access
      to "buzz-pollinating" bees, including Xylocopa species (carpenter bees), which
      can remove pollen by sonication. This is one of very few reports of paedomorphic
      specialization, and, as far as we are aware, the first documented case of a rapid
      reversal to specialized pollination in a lineage of plants that had previously
      switched from specialized to generalized pollination in conjunction with
      dispersing to a new region.

PMID- 23550769
TI  - The evolution of locomotor rhythmicity in tetrapods.
AB  - Differences in rhythmicity (relative variance in cycle period) among mammal,
      fish, and lizard feeding systems have been hypothesized to be associated with
      differences in their sensorimotor control systems. We tested this hypothesis by
      examining whether the locomotion of tachymetabolic tetrapods (birds and mammals)
      is more rhythmic than that of bradymetabolic tetrapods (lizards, alligators,
      turtles, salamanders). Species averages of intraindividual coefficients of
      variation in cycle period were compared while controlling for gait and substrate.
      Variance in locomotor cycle periods is significantly lower in tachymetabolic than
      in bradymetabolic animals for datasets that include treadmill locomotion, non
      treadmill locomotion, or both. When phylogenetic relationships are taken into
      account the pooled analyses remain significant, whereas the non-treadmill and the
      treadmill analyses become nonsignificant. The co-occurrence of relatively high
      rhythmicity in both feeding and locomotor systems of tachymetabolic tetrapods
      suggests that the anatomical substrate of rhythmicity is in the motor control
      system, not in the musculoskeletal components.

PMID- 23550771
TI  - The expression of hypoxia-inducible factor-1 in primary brain tumors.
AB  - PURPOSE: Primary brain tumors are common type of neoplasms. The most common are
      astrocytic tumors, so do meningiomas of various grades. The etiology is still
      unknown; however, there are lots of data presenting new theories about genetic
      alterations responsible for low- or high-grade astrocytic tumors development as
      well as meningiomas, despite this the results are divergent. The aim of the study
      was to evaluate hypoxia-inducible factor-1 (HIF-1) expression in meningiomas and
      astrocytic tumors of various grades. MATERIAL AND METHODS: One hundred six cases
      of astrocytic tumors were divided into diffused astrocytoma (24 cases),
      anaplastic astrocytoma (40 cases) and glioblastoma groups (42 cases). Among
      glioblastoma group, 30 cases were secondary glioblastoma. One hundred fifty-four
      meningioma cases were divided as low-grade meningioma (G1: 104 cases) and high
      grade meningioma groups (G2: 43 cases and G3: 7 cases). Twelve low-grade
      meningiomas transformed into high-grade tumors, 17 low-grade meningiomas recur
      within 12 years. HIF-1 expression was estimated using immunohistochemistry under
      the light microscope. Statistical analysis was performed in all examined groups.
      RESULTS: HIF-1 expression was observed in 37.5% cases of diffused astrocytomas,
      in anaplastic astrocytomas 27.5% tumors were HIF-1 positive, in the glioblastoma
      goup HIF-1 expression was observed in 83.3% cases. All secondary glioblastomas
      were positive for HIF-1. Low-grade meningiomas were positive for HIF-1 in 55.7%,
      in high-grade meningiomas, HIF-1 expression was observed in 84%. All meningiomas,
      which progressed from low- to high-grade meningiomas, were HIF-1 positive.
      CONCLUSION: HIF-1 expression is associated with the development and progression
      of both astrocytic tumors and meningiomas.

PMID- 23550770
TI  - The importance of mosquito behavioural adaptations to malaria control in Africa.
AB  - Over the past decade the use of long-lasting insecticidal nets (LLINs), in
      combination with improved drug therapies, indoor residual spraying (IRS), and
      better health infrastructure, has helped reduce malaria in many African countries
      for the first time in a generation. However, insecticide resistance in the vector
      is an evolving threat to these gains. We review emerging and historical data on
      behavioral resistance in response to LLINs and IRS. Overall the current
      literature suggests behavioral and species changes may be emerging, but the data
      are sparse and, at times unconvincing. However, preliminary modeling has
      demonstrated that behavioral resistance could have significant impacts on the
      effectiveness of malaria control. We propose seven recommendations to improve
      understanding of resistance in malaria vectors. Determining the public health
      impact of physiological and behavioral insecticide resistance is an urgent
      priority if we are to maintain the significant gains made in reducing malaria
      morbidity and mortality.

PMID- 23550772
TI  - New inhibitors of ROS generation and T-cell proliferation from Myrtus communis.
AB  - Phytochemical investigation on Myrtus communis Linn. afforded myrtucommuacetalone
      (1) with an unprecedented carbon skeleton and a new phloroglucinol-type compound,
      myrtucommulone M (2), along with four known constituents 3-6. Their structures
      were established by extensive analyses of NMR and mass spectral data as well as
      by single-crystal X-ray diffraction studies. These constituents were evaluated
      for their ability to modulate the immune response, based on their effects on
      various components of immune system. Compounds 1 and 5 exhibited significant
      inhibitory effect against nitric oxide (NO(*)) production. Compound 1 also
      exhibited significant antiproliferative activity (IC50 < 0.5 MUg/mL) against T
      cell proliferation. Myricetin (3) exerted a significant inhibition (IC50 = 1.6
      MUg/mL) on zymosan-stimulated whole blood phagocytes ROS production. Compounds 1
      and 3 were active against PMA-stimulated ROS generation.

PMID- 23550773
TI  - Efficacy of HLA-matched platelet transfusions for patients with hypoproliferative
      thrombocytopenia: a systematic review.
AB  - BACKGROUND: HLA-matched platelets (PLTs) are widely used to transfuse patients
      but the effectiveness of HLA matching has not been well defined and the cost is
      approximately five times the cost of preparing the random-donor PLTs. The
      objective of this systematic review was to determine whether HLA-matched PLTs
      lead to a reduction in mortality; reduction in frequency or severity of
      hemorrhage; reduction in HLA alloimmunization, refractoriness, or PLT
      utilization; or improvement in PLT count increment in patients with
      hypoproliferative thrombocytopenia. STUDY DESIGN AND METHODS: We conducted a
      literature search of MEDLINE, Cochrane Controlled Register of Clinical Trials,
      EMBASE, and PubMed databases to April 2012. RESULTS: A total of 788 citations
      were reviewed and 30 reports were included in the analysis. Most studies did not
      include technologies currently in use for HLA typing or detection of HLA
      antibodies as 75% were conducted before the year 2000. None of the studies were
      adequately powered to detect an effect on mortality or hemorrhage. HLA-matched
      PLTs did not reduce alloimmunization and refractoriness rates beyond that offered
      by leukoreduction, and utilization was not consistently improved. HLA-matched
      PLTs led to better 1-hour posttransfusion count increments and percentage of PLT
      recovery in refractory patients; however, the effect at 24 hours was
      inconsistent. CONCLUSION: The correlation of the PLT increment with other
      clinical outcomes and the effect of leukoreduction on HLA-matched PLT transfusion
      could not be determined. Prospective studies utilizing current technology and
      examining clinical outcomes are necessary to demonstrate the effectiveness of HLA
      matched PLT transfusion.

PMID- 23550774
TI  - Neuroprotective activities of catalpol against CaMKII-dependent apoptosis induced
      by LPS in PC12 cells.
AB  - BACKGROUND AND PURPOSE: Neurodegenerative diseases present progressive
      neurological disorder induced by cell death or apoptosis. Catalpol, an iridoid
      glucoside isolated from the root of Rehmannia glutinosa Libosch, is present in a
      wide range of plant families. Although catalpol is an effective anti-apoptotic
      agent in LPS-induced neurodegeneration, the underlying mechanism has not been
      established. Here we have identified some of the mechanisms involved the
      prevention by catalpol of apoptosis induced by LPS in an experimental model of
      neurodegeneration in vitro. EXPERIMENTAL APPROACH: Apoptosis was induced by
      adding LPS (80 ng.mL(-1)) to pheochromocytoma (PC12) cells, pretreated with
      catalpol for 12 h. We measured intracellular reactive oxygen species (ROS),
      apoptosis and intracellular calcium concentration ([Ca(2+)]i) by flow cytometry
      or laser confocal scanning microscopy. We also analysed the protein expression of
      Bcl-2, Bax and Ca(2+)-calmodulin-dependent protein kinase II (CaMKII)-dependent
      apoptosis signal-regulating kinase-1 (ASK-1)/JNK/p38 signalling pathway in PC12
      cells by Western blot. KEY RESULTS: Catalpol stimulated expression of Bcl-2 and
      inhibited the expression of Bax. Catalpol also attenuated the increase in Ca(2+)
      concentration induced by LPS in PC12 cells and down-regulated CaMK
      phosphorylation. The CaMKII-dependent ASK-1/JNK/p38 signalling cascade was
      blocked by catalpol. All these changes were accompanied by a decrease of
      apoptosis induced by LPS in PC12 cells. CONCLUSIONS AND IMPLICATIONS: The data
      presented here provide new mechanistic insights into the links between the CaMKII
      dependent ASK-1/JNK/p38 signalling pathway and the protective effect of catalpol
      on apoptosis induced by LPS in PC12 cells.

PMID- 23550775
TI  - Phosphohistone-H3 and Ki-67 immunostaining in cutaneous pilar leiomyoma and
      leiomyosarcoma (atypical intradermal smooth muscle neoplasm).
AB  - BACKGROUND: The mitotic index is important in the assessment of tumors such as
      leiomyoma (LM) and leiomyosarcoma (LMS), which may exhibit a range of cytological
      atypia. The mitotic marker phosphohistone-H3 (PHH3) was shown to improve
      interobserver and intraobserver variability in many tumors. MATERIALS AND
      METHODS: We evaluated the mitotic index in 20 pilar LM and cutaneous LMS using
      PHH3 and hematoxylin and eosin (H&E)-stained sections. Ki-67 staining
      characteristics of the tumors were also assessed. RESULTS: Mitotic figures were
      more easily identified within PHH3 sections. The mitotic index per 10 high power
      fields (HPF) on the PHH3 stain was slightly higher than H&E both in the LM (mean
      0.1, range 0-1 vs. mean 0) and LMS groups (mean 8.6 vs. 8.0 with range of 1-24
      for both stains). The difference in mitotic index between the two stains was not
      statistically significant in either group (p = 0.7). The Ki-67 proliferative
      index showed a statistically significant correlation with a diagnosis of LMS.
      CONCLUSION: PHH3 immunostain can simplify counting of mitotic figures in
      cutaneous smooth muscle neoplasms, especially those with many pyknotic nuclei,
      and may help to reduce interobserver variability. Ki-67 staining may also be of
      help in establishing a diagnosis of LMS.

PMID- 23550776
TI  - Cattle-caused fatalities in a province of western Turkey: 1996-2010 autopsy
      results.
AB  - Cattle-caused injuries and deaths are much more than predicted. The aim of this
      research is to determine the prevalence of cattle-caused fatalities and the
      factors affecting it in a province of western Turkey. The court files on cattle
      caused fatalities during a 15-year period between 1996 and 2010 were explored.
      The proportion of forensic-qualified deaths from the total of 3753 was 0.9%
      (35/3753). Most of the cases were between the ages of 18 and 65 (60%). Most
      deaths occurred in the spring and summer months compared with autumn and winter
      months (9 and 22 vs. 3 and 1, respectively). The mortality rate was much higher
      in men compared with women (94.3% and 5.7%, respectively). The majority of deaths
      were caused by injuries on the chest (71.4%). The reason for most deaths was due
      to hemopneumothorax and lung injury (71.4%). Predicting the behavior of cattle
      may not always be possible, as such, it is advisable that one wears protective
      equipment when dealing with cattle.

PMID- 23550777
TI  - Measurement of naphthalene uptake by combustion soot particles.
AB  - In this study, we designed and constructed an experimental laboratory apparatus
      to measure the uptake of volatile organic compounds (VOCs) by soot particles.
      Results for the uptake of naphthalene (C10H8) by soot particles typical of those
      found in the exhaust of an aircraft engine are reported in this paper. The
      naphthalene concentration in the gas phase and naphthalene attached to the
      particles were measured simultaneously by a heated flame ionization detector
      (HFID) and a time-of-flight aerosol mass spectrometer (ToF AMS), respectively.
      The uptake coefficient for naphthalene on soot of (1.11 +/- 0.06) * 10(-5) at 293
      K was determined by fitting the HFID and AMS measurements of gaseous and
      particulate naphthalene to a kinetic model of uptake. When the gaseous
      concentration of naphthalene is kept below the saturation limit during these
      experiments, the uptake of naphthalene can be considered the dry mass
      accommodation coefficient.

PMID- 23550778
TI  - Resistance to lateral luxation of two canine total elbow replacement systems
      under variable mechanical loads.
AB  - OBJECTIVE: To measure the loads required to induce lateral luxation of the Iowa
      State University (ISU) elbow implant, a modified elbow implant, and the normal
      canine elbow with the ligaments and joint capsule removed. STUDY DESIGN:
      Mechanical testing on cadaveric specimens SAMPLE POPULATION: Twelve thoracic
      limbs were harvested from adult, medium sized dogs that had been euthanatized for
      reasons unrelated to the study. METHODS: The torque needed for luxation was
      identified on potted cadaver elbows under variable axial load and compared to ISU
      implants and modified implants. Shear force needed to induce medial and lateral
      luxation were collected for the 2-implant designs at 10, 109, 209, and 342 N of
      axial load based on. Shear force needed to induce lateral luxation were collected
      for the normal elbows (with and without an anconeal process) at 10 N of axial
      load. RESULTS: The modified implant had 5* higher torque at luxation than the ISU
      implant and cadavers elbows for both internal and external rotation. Luxation
      during shear testing was significantly higher in cadaver elbows when compared to
      either implant but the modified implant was 4-7* more resistant then the ISU
      implant. CONCLUSION: The modified total elbow replacement implant may reduce
      lateral luxation in vivo by increased resistance to shear and torsional forces.

PMID- 23550779
TI  - The use of ophthalmic viscosurgical devices during donor's corneal harvesting.
AB  - PURPOSE OF THE STUDY: To evaluate the protective effect of Biolon (sodium
      hyaluronate 1%) use on corneal endothelium, during donor's corneal harvesting.
      MATERIALS AND METHODS: A prospective, randomized, double blind, comparative study
      was performed on 120 corneas donated from 60 donors. One cornea from each donor
      (n = 60) was harvested using intracameral injection of ophthalmic viscosurgical
      device (OVD), and the fellow cornea with no use of OVD (n = 60, control group).
      Endothelial cell density (ECD) values were obtained at the center of each corneal
      graft with a specular microscope one day after harvesting. RESULTS: ECD in the
      OVD group were 2839 +/- 412.5 cells/mm(2) and in the control group 2748 +/- 429.7
      cells/mm(2). (p = 0.03). Distribution curve of the difference in ECD between the
      OVD and no OVD eyes showed that 47% of the donors had > 100 cells/mm2 difference,
      and 32% of donors had >200 cells/mm(2) difference in favor of the OVD group.
      CONCLUSIONS: Intracameral OVD injection during corneal graft harvesting may
      protect the endothelium from the mechanical damage induced during the procedure.
      Further investigation is needed before routine the use of intracameral OVD should
      be considered in this setting.

PMID- 23550780
TI  - Stable tetraaryldiphosphine radical cation and dication.
AB  - Salts containing tetraaryldiphosphine radical cation 1(*+) and dication 1(2+)
      have been isolated and structurally characterized. Radical 1(*+) has a relaxed
      pyramidal geometry, while dication 1(2+) prefers a planar, olefin-like geometry
      with a two-electron pi bond. The alteration of the geometries of the
      tetraaryldiphosphine upon oxidation is rationalized by the nature of the bonding.
      The EPR spectrum showed that the spin density of radical 1(*+) is mainly
      localized on phosphorus atoms, which is supported by theoretical calculation.

PMID- 23550781
TI  - Nutritional strategies to attenuate muscle disuse atrophy.
AB  - Situations such as recovery from injury or illness require otherwise healthy
      humans to undergo periods of disuse, which lead to considerable losses of
      skeletal muscle mass and, subsequently, numerous negative health consequences. It
      has been established that prolonged disuse (>10 days) leads to a decline in basal
      and postprandial rates of muscle protein synthesis, without an apparent change in
      muscle protein breakdown. It also seems, however, that an early and transient (1
      5 days) increase in basal muscle protein breakdown may also contribute to disuse
      atrophy. A period of disuse reduces energy requirements and appetite.
      Consequently, food intake generally declines, resulting in an inadequate dietary
      protein consumption to allow proper muscle mass maintenance. Evidence suggests
      that maintaining protein intake during a period of disuse attenuates disuse
      atrophy. Furthermore, supplementation with dietary protein and/or essential amino
      acids can be applied to further aid in muscle mass preservation during disuse.
      Such strategies are of particular relevance to the older patient at risk of
      developing sarcopenia. More work is required to elucidate the impact of disuse on
      basal and postprandial rates of muscle protein synthesis and breakdown. Such
      information will provide novel targets for nutritional interventions to further
      attenuate muscle disuse atrophy and, as such, support healthy aging.

PMID- 23550782
TI  - Meeting and exceeding dairy recommendations: effects of dairy consumption on
      nutrient intakes and risk of chronic disease.
AB  - The 2010 Dietary Guidelines for Americans indicate the US population is
      experiencing an epidemic of overweight and obesity while maintaining a nutrient
      poor, energy-dense diet associated with an increased risk of osteoarthritis,
      cardiovascular disease, and type 2 diabetes. To build upon the review of
      published research in the Report of the Dietary Guidelines Advisory Committee on
      the Dietary Guidelines for Americans, 2010, this article aims to review the
      scientific literature pertaining to the consumption of dairy foods and the
      effects of dairy consumption on nutrient intakes and chronic disease risk
      published between June 2010, when the report was released, and September 2011.
      PubMed was searched for articles using the following key words: dairy, milk,
      nutrient intake, bone health, body composition, cardiovascular disease, type 2
      diabetes, and blood pressure. Evidence indicates that increasing dairy
      consumption to the recommended amount, i.e., three servings daily for individuals
      >=9 years of age, helps close gaps between current nutrient intakes and
      recommendations. Consuming more than three servings of dairy per day leads to
      better nutrient status and improved bone health and is associated with lower
      blood pressure and reduced risk of cardiovascular disease and type 2 diabetes.

PMID- 23550783
TI  - Designing culturally sensitive dietary interventions for African Americans:
      review and recommendations.
AB  - Despite consensus that dietary intervention programs should be culturally
      sensitive, relatively little is known about approaches to developing culturally
      sensitive interventions. With a focus on African Americans, the present review
      summarizes the existing literature on cultural considerations when working with
      this population and suggests strategies for the development of culturally
      sensitive interventions to modify the dietary practices of African Americans.
      Interventions to improve dietary behaviors and nutritional status among African
      Americans are needed urgently in order to reduce morbidity and mortality from
      diet-related diseases in this population. Findings are intended to serve as a
      guide for future research and practice on culturally sensitive approaches for
      effecting such changes.

PMID- 23550784
TI  - Mechanistic perspective on the relationship between pyridoxal 5'-phosphate and
      inflammation.
AB  - A variety of inflammatory disease conditions have been found to be associated
      with low levels of plasma pyridoxal 5'-phosphate (PLP), the active form of
      vitamin B6 , without any indication of a lower dietary intake of vitamin B6 ,
      excessive catabolism of the vitamin, or congenital defects in its metabolism. The
      present review was conducted to examine the existing literature in this regard.
      Current evidence suggests that the inverse association between plasma PLP and
      inflammation may be the result of mobilization of this coenzyme to the site of
      inflammation, for use by the PLP-dependent enzymes of the kynurenine pathway of
      tryptophan degradation, metabolism of the immunomodulatory sphingolipids,
      ceramide and sphingosine 1-phosphate, and for serine hydroxymethylase for immune
      cell proliferation.

PMID- 23550785
TI  - Ginger (Zingiber officinale) and chemotherapy-induced nausea and vomiting: a
      systematic literature review.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of
      cytotoxic treatment. It continues to affect a significant proportion of patients
      despite the widespread use of antiemetic medication. In traditional medicine,
      ginger (Zingiber officinale) has been used to prevent and treat nausea in many
      cultures for thousands of years. However, its use has not been confirmed in the
      chemotherapy context. To determine the potential use of ginger as a prophylactic
      or treatment for CINV, a systematic literature review was conducted. Reviewed
      studies comprised randomized controlled trials or crossover trials that
      investigated the anti-CINV effect of ginger as the sole independent variable in
      chemotherapy patients. Seven studies met the inclusion criteria. All studies were
      assessed on methodological quality and their limitations were identified. Studies
      were mixed in their support of ginger as an anti-CINV treatment in patients
      receiving chemotherapy, with three demonstrating a positive effect, two in favor
      but with caveats, and two showing no effect on measures of CINV. Future studies
      are required to address the limitations identified before clinical use can be
      recommended.

PMID- 23550786
TI  - Effects of different instructional constraints on task performance and emergence
      of coordination in children.
AB  - The objectives of this study were to determine the impact of different
      instructional constraints on standing board jump (sbj) performance in children
      and understand the underlying changes in emergent movement patterns. Two groups
      of novice participants were provided with either externally or internally focused
      attentional instructions during an intervention phase. Pre- and post-test
      sessions were undertaken to determine changes to performance and movement
      patterns. Thirty-six primary fourth-grade male students were recruited for this
      study and randomly assigned to either an external, internal focus or control
      group. Different instructional constraints with either an external focus (image
      of the achievement) or an internal focus (image of the act) were provided to the
      participants. Performance scores (jump distances), and data from key kinematic
      (joint range of motion, ROM) and kinetic variables (jump impulses) were
      collected. Instructional constraints with an emphasis on an external focus of
      attention were generally more effective in assisting learners to improve jump
      distances. Intra-individual analyses highlighted how enhanced jump distances for
      successful participants may be concomitant with specific changes to kinematic and
      kinetic variables. Larger joint ROM and adjustment to a comparatively larger
      horizontal impulse to a vertical impulse were observed for more successful
      participants at post-test performance. From a constraints-led perspective, the
      inclusion of instructional constraints encouraging self-adjustments in the
      control of movements (i.e., image of achievement) had a beneficial effect on
      individuals performing the standing broad jump task. However, the advantage of
      using an external focus of attentional instructions could be task- and individual
      specific.

PMID- 23550787
TI  - A search for interaction among combinations of drugs of abuse and the use of
      isobolographic analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Individuals who abuse drugs usually use more than
      one substance. Toxic consequences of single and multi-drug use are well
      documented in the Treatment Episodes Data Set that lists drug combinations that
      result in hospital admissions. Using this list as a guide, we focused our
      attention on combinations that result in the most hospital admissions and
      searched the PubMed database with the objective of determining the number of such
      publications and, in particular, those that used the term synergism in their
      titles or abstracts. COMMENT: Using the search criteria produced an extensive
      list of published articles. However, a further intersection of the search terms
      with the term isobole revealed a surprisingly small number of literature reports.
      WHAT IS NEW AND CONCLUSION: Because the method of isoboles is the most common
      quantitative method for distinguishing between drug synergism and simple
      additivity, the small number of investigations that actually employed this
      quantification suggests that the term synergism is not properly documented in
      describing the toxicity among abused substances. The possible reasons for this
      lack of quantification may be related to a misunderstanding of the modelling
      equations. To help rectify this possible hurdle to understanding and clinical
      utility, the theory and modelling are discussed here.

PMID- 23550788
TI  - Unconscious racist bias: barrier to a diverse nursing faculty.

PMID- 23550789
TI  - Improving technology literacy and skills among minority nursing students.

PMID- 23550790
TI  - Providing cultural experiences through two-way international exchange.

PMID- 23550791
TI  - A randomised, non-crossover study of the GuardianCPV Laryngeal Mask versus the
      LMA Supreme in paralysed, anaesthetised female patients.
AB  - We investigated the hypothesis that the oropharyngeal leak pressure would differ
      between the GuardianCPVTM and the LMA SupremeTM in anaesthetised patients. We
      randomly assigned 120 patients to receive either the GuardianCPV or the LMA
      Supreme for airway management. Oropharyngeal leak pressure was measured during
      cuff inflation from 0 to 40 ml in 10-ml steps. In addition, intracuff pressure,
      fibreoptic position of the airway and drain tube, device insertion success,
      ventilation success, blood staining and airway morbidity were determined. Mean
      (SD) oropharyngeal leak pressures for clinically acceptable cuff volumes of 20-40
      ml were 31 (7) cmH2O for the GuardianCPV and 27 (7) cmH2O for the LMA Supreme (p
      < 0.0001); mean (SD) intracuff pressures were 68 (33) cmH2O and 88 (43) cmH2O (p
      < 0.0001), respectively. We found no differences in device insertion success,
      ventilation success, fibreoptic position of the airway and drain tube, blood
      staining or airway morbidity. We conclude that the oropharyngeal leak pressure is
      better for the GuardianCPV than for the LMA Supreme in anaesthetised patients.

PMID- 23550793
TI  - Addressing the questions of tomorrow: melphalan and new combinations as
      conditioning regimens before autologous hematopoietic progenitor cell
      transplantation in multiple myeloma.
AB  - INTRODUCTION: The role of high-dose chemotherapy (HDC) followed by autologous
      progenitor cell transplantation (auto-HPCT) in the treatment of multiple myeloma
      (MM) continues to evolve in the novel agent era. Administration of high-dose
      melphalan (HDM) is considered the standard conditioning regimen. Nevertheless,
      several attempts have recently been made to improve the conditioning phase of the
      HDC procedure. AREAS COVERED: We reviewed all the reported experiences and
      illustrated current knowledge in the field of conditioning regimens. EXPERT
      OPINION: For fit MM patients, HDC followed by auto-HPCT remains the standard of
      care. The available data confirm that melphalan (MEL) 200 mg/m(2) should continue
      to be considered the gold standard conditioning regimen, with dose reduction
      based on age and renal function. Targeting exposure to MEL by using area under
      the curve is a particularly appealing approach that could be explored to maximize
      efficacy and minimize toxicity of this drug. Other strategies are currently being
      evaluated in different trials, and the most interesting areas of research involve
      the incorporation of newer agents like bortezomib (BOR) into conditioning
      regimens. Moreover, intravenous busulfan has become available and this
      formulation may reduce toxicity and result in greater efficacy in association
      with MEL-based conditioning.

PMID- 23550792
TI  - Selection for drinking in the dark alters brain gene coexpression networks.
AB  - BACKGROUND: Heterogeneous stock (HS/NPT) mice have been used to create lines
      selectively bred in replicate for elevated drinking in the dark (DID). Both
      selected lines routinely reach a blood ethanol (EtOH) concentration (BEC) of 1.00
      mg/ml or greater at the end of the 4-hour period of access in Day 2. The
      mechanisms through which genetic differences influence DID are currently unclear.
      Therefore, the current study examines the transcriptome, the first stage at which
      genetic variability affects neurobiology. Rather than focusing solely on
      differential expression (DE), we also examine changes in the ways that gene
      transcripts collectively interact with each other, as revealed by changes in
      coexpression patterns. METHODS: Naive mice (N = 48/group) were genotyped using
      the Mouse Universal Genotyping Array, which provided 3,683 informative markers.
      Quantitative trait locus (QTL) analysis used a marker-by-marker strategy with the
      threshold for a significant logarithm of odds (LOD) set at 10.6. Gene expression
      in the ventral striatum was measured using the Illumina Mouse 8.2 array.
      Differential gene expression and the weighted gene coexpression network analysis
      (WGCNA) were implemented largely as described elsewhere. RESULTS: Significant
      QTLs for elevated BECs after DID were detected on chromosomes 4, 14, and 16; the
      latter 2 were associated with gene-poor regions. None of the QTLs overlapped with
      known QTLs for EtOH preference drinking. Ninety-four transcripts were detected as
      being differentially expressed in both selected lines versus HS controls; there
      was no overlap with known preference genes. The WGCNA revealed 2 modules as
      showing significant effects of both selections on intramodular connectivity. A
      number of genes known to be associated with EtOH phenotypes (e.g., Gabrg1, Glra2,
      Grik1, Npy2r, and Nts) showed significant changes in connectivity. CONCLUSIONS:
      We found marked and consistent effects of selection on coexpression patterns; DE
      changes were more modest and less concordant. The QTLs and differentially
      expressed genes detected here are distinct from the preference phenotype. This is
      consistent with behavioral data and suggests that the DID and preference
      phenotypes are markedly different genetically.

PMID- 23550794
TI  - Macroscopic highly aligned DNA nanowires created by controlled evaporative self
      assembly.
AB  - By subjecting DNA aqueous solution to evaporate in a curve-on-flat geometry that
      was composed of either a spherical lens or a cylindrical lens situated on a flat
      substrate, a set of highly aligned DNA nanowires in the forms of spokes and
      parallel stripes over a macroscopic area (i.e., millimeter scale) were
      successfully created. The DNA molecules were stretched and aligned on polymer
      coated substrate by the receding meniscus. The imposed curve-on-flat geometry
      provided a unique environment for controlling the flow within the evaporating
      solution by eliminating temperature gradient and possible convective instability
      and, thus, regulated the formation of DNA nanowires. Such controlled evaporative
      self-assembly is remarkably easy to implement and opens up a new avenue for
      crafting large-scale DNA-based nanostructures in a simple and cost-effective
      manner, dispensing with the need for lithography techniques.

PMID- 23550795
TI  - Factors influencing outcome in patients with cardiac arrest in the ICU.
AB  - BACKGROUND: Post-arrest variables associated with long-term survival after
      cardiopulmonary resuscitation (CPR) in intensive care unit (ICU) patients remain
      unclear. This study was designed to identify pre- and intra-arrest factors
      associated with survival 3 months after CPR in ICU patients and to identify post
      arrest factors associated with long-term survival in those who survived 24 h
      after CPR. METHODS: A total of 131 ICU patients undergoing CPR from January 2009
      to June 2010 were included. Data were retrospectively analysed and categorized
      based on the Utstein template. RESULTS: The overall survival rate 3 months after
      CPR was 20.6%. Logistic regression analysis revealed that acute physiology and
      chronic health evaluation (APACHE) II score (odds ratio, 95% confidence interval,
      0.87 [0.83-0.93]; P < 0.001), ventricular tachycardia/ventricular fibrillation
      (VT/VF, 5.55 [1.55-19.83]; P = 0.032), and normoxia during CPR (4.45 [1.34
      14.71]; P = 0.045) were significant independent pre- and intra-arrest predictors
      of 3-month survival after CPR in ICU patients. Fifty-seven patients survived 24 h
      after CPR, and their 3-month survival rate was 47.4%. Early enteral nutrition
      (9.94 [1.96-50.43]; P = 0.030) and normoxia after return of spontaneous
      circulation (10.75 [2.03-55.56]; P = 0.030) were predictive of 3-month survival
      in patients who survived 24 h after CPR. CONCLUSIONS: Normoxia during CPR and
      VT/VF were predictors of long-term survival after CPR in ICU patients. In
      patients surviving 24 h after CPR, initiation of enteral nutrition within 48 h
      and maintenance of normoxia were associated with a positive outcome.

PMID- 23550796
TI  - I thought we were good: social cognition, figurative language, and adolescent
      psychopathology.
AB  - BACKGROUND: Language has been shown to play a critical role in social cognitive
      reasoning in preschool and school-aged children, but little research has been
      conducted with adolescents. During adolescence, the ability to understand
      figurative language becomes increasingly important for social relationships and
      may affect social adjustment. This study investigated the contribution of
      structural and figurative language to social cognitive skills in adolescents who
      present for mental health services and those who do not. METHOD: One hundred and
      thirty-eight adolescents referred to mental health centers (clinic group) and 186
      nonreferred adolescents (nonclinic group) aged 12-17 were administered measures
      of structural and figurative language, working memory, and social cognitive
      problem solving. RESULTS: We found that adolescents in the clinic group
      demonstrated less mature social problem solving overall, but particularly with
      respect to anticipating and overcoming potential obstacles and conflict
      resolution compared with the nonclinic group. In addition, results demonstrated
      that age, working memory, and structural and figurative language predicted social
      cognitive maturity in the clinic group, but only structural language was a
      predictor in the nonclinic group. CONCLUSIONS: Social problem solving may be
      particularly difficult for adolescents referred for mental health services and
      places higher demands on their cognitive and language skills compared with
      adolescents who have never been referred for mental health services.

PMID- 23550797
TI  - Effect of post-trial L-NAME administration on cocaine sensitization.
AB  - This study determined if Nomega-nitro-L-arginine methyl ester hydrochloride (L
      NAME) administered after the cocaine-conditioning trial attenuated the
      development of sensitization to cocaine's locomotor-stimulating effect and
      secondly, determined if L-NAME blocked conditioned-locomotor activity (LMA)
      elicited by a saline-challenge injection. Results revealed that cocaine-injected
      animals (10 mg/kg, i.p.) showed enhanced locomotor activity across the three
      conditioning trials (all p's < .05). Cocaine-injected animals administered L-NAME
      (30 mg/kg, i.p.) after each conditioning trial showed a slight increase in
      cocaine-stimulated LMA from the first to the second conditioning trial (all p's <
      .05) and no further increases in LMA thereafter. A saline-challenge injection
      administered 72 hr after the last conditioning trial revealed that cocaine
      injected animals displayed as much locomotor stimulation to a saline injection as
      they did during their initial exposure to cocaine on the first conditioning trial
      - indicating the development of cocaine-conditioned LMA. The present findings
      show that L-NAME administered after the cocaine-conditioning trial attenuates the
      development of sensitization to cocaine's locomotor-stimulating effect. The
      failure of L-NAME to block cocaine-conditioned LMA suggests that the
      pharmacological and conditioning mechanisms of sensitization can be dissociated.
      It is unlikely that L-NAME's effect is due to a sedative action produced by
      residual L-NAME since animals administered L-NAME (30 mg/kg, i.p.) for 10
      consecutive days exhibited a similar responsiveness to a cocaine challenge
      administered 3 and 10 days following the termination of L-NAME administration.
      These data support a role for nitric oxide's involvement in the neuroadaptive
      responses that result from continued stimulant administration and demonstrate the
      importance of conditioned drug effects.

PMID- 23550798
TI  - Isolation and photoinduced conversion of 6-epi-stephacidins from Aspergillus
      taichungensis.
AB  - Three prenylated indole alkaloids with a rare anti bicyclo-[2.2.2]diazaoctane
      core ring (5-7) were isolated from Aspergillus taichungensis. The structures
      including absolute configurations were elucidated based on NMR, X-ray, and CD
      methods. (+)-Versicolamides B and C (8-9) which contain a spiro-center, together
      with seven analogues (7, 10-15), were isolated as photoinduced conversion
      products of 6. Biological evaluation indicated that 6 and 7 exhibited significant
      cytotoxicities with IC50 values in the low micromolar range.

PMID- 23550799
TI  - Mullerian and eccrine cutaneous ciliated cysts: two different entities? The
      contribution of WT-1 and PAX8 to diagnosis.

PMID- 23550800
TI  - Evolution of TUNEL-labeling in the rat lens after in vivo exposure to just above
      threshold dose UVB.
AB  - PURPOSE/AIM: To quantitatively analyse the evolution of TUNEL-labeling, after in
      vivo exposure to UVB. METHODS: Altogether, 16 Sprague Dawley rats were
      unilaterally exposed in vivo for 15 min to close to threshold dose, 5 kJ/m(2), of
      ultraviolet radiation in the 300 nm wavelength region. Animals were sacrificed in
      groups of 4 at 1, 5, 24 and 120 h after exposure. For each animal, both eye
      globes were removed and frozen. The frozen eye was cryo-sectioned in 10 um thick
      midsagittal sections. From each globe, three midsagittal sections with at least
      five sections interval in between were mounted on a microscope slide. Sections
      were TUNEL-labeled and counter stained with DAPI. For quantification of
      apoptosis, a fluorescence microscope was used. In sections with a continuous
      epithelial cell surface, the number of lens epithelial cell nuclei and the number
      of TUNEL-positive epithelial cell nuclei was counted. The total number of TUNEL
      positive epithelial cell nuclei for all three sections of one lens in relation to
      the total number of epithelial cell nuclei for all three sections of the same
      lens was compared between exposed and contralateral not exposed lens for each
      animal. RESULTS: The relative difference of the fraction of TUNEL-positive nuclei
      between exposed and contralateral not exposed lens increased gradually, peaked in
      the time interval 5-120 h after exposure, and then declined. CONCLUSIONS: Close
      to threshold dose of UVB induces TUNEL-labeling that peaks in the time window 5
      120 h after exposure to UVB.

PMID- 23550802
TI  - Simultaneous reduction of particulate matter and NO(x) emissions using 4-way
      catalyzed filtration systems.
AB  - The next generation of diesel emission control devices includes 4-way catalyzed
      filtration systems (4WCFS) consisting of both NOx and diesel particulate matter
      (DPM) control. A methodology was developed to simultaneously evaluate the NOx and
      DPM control performance of miniature 4WCFS made from acicular mullite, an
      advanced ceramic material (ACM), that were challenged with diesel exhaust. The
      impact of catalyst loading and substrate porosity on catalytic performance of the
      NOx trap was evaluated. Simultaneously with NOx measurements, the real-time solid
      particle filtration performance of catalyst-coated standard and high porosity
      filters was determined for steady-state and regenerative conditions. The use of
      high porosity ACM 4-way catalyzed filtration systems reduced NOx by 99% and solid
      and total particulate matter by 95% when averaged over 10 regeneration cycles. A
      "regeneration cycle" refers to an oxidizing ("lean") exhaust condition followed
      by a reducing ("rich") exhaust condition resulting in NOx storage and NOx
      reduction (i.e., trap "regeneration"), respectively. Standard porosity ACM 4-way
      catalyzed filtration systems reduced NOx by 60-75% and exhibited 99.9% filtration
      efficiency. The rich/lean cycling used to regenerate the filter had almost no
      impact on solid particle filtration efficiency but impacted NOx control. Cycling
      resulted in the formation of very low concentrations of semivolatile nucleation
      mode particles for some 4WCFS formulations. Overall, 4WCFS show promise for
      significantly reducing diesel emissions into the atmosphere in a single control
      device.

PMID- 23550801
TI  - Identification through high-throughput screening of 4'-methoxyflavone and 3',4'
      dimethoxyflavone as novel neuroprotective inhibitors of parthanatos.
AB  - BACKGROUND AND PURPOSE: The current lack of disease-modifying therapeutics to
      manage neurological and neurodegenerative conditions justifies the development of
      more efficacious agents. One distinct pathway leading to neuronal death in these
      conditions and which represents a very promising and attractive therapeutic
      target is parthanatos, involving overactivation of PARP-1. We therefore sought to
      identify small molecules that could be neuroprotective by targeting the pathway.
      EXPERIMENTAL APPROACH: Using HeLa cells, we developed and optimized an assay for
      high-throughput screening of about 5120 small molecules. Structure-activity
      relationship (SAR) study was carried out in HeLa and SH-SY5Y cells for molecules
      related to the initial active compound. The neuroprotective ability of each
      active compound was tested in cortical neuronal cultures. KEY RESULTS: 4'
      Methoxyflavone (4MF) showed activity by preventing the decrease in cell viability
      of HeLa and SH-SY5Y cells caused by the DNA-alkylating agent, N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), which induces parthanatos. A similar compound from the
      SAR study, 3',4'-dimethoxyflavone (DMF), also showed significant activity. Both
      compounds reduced the synthesis and accumulation of poly (ADP-ribose) polymer and
      protected cortical neurones against cell death induced by NMDA. CONCLUSIONS AND
      IMPLICATIONS: Our data reveal additional neuroprotective members of the flavone
      class of flavonoids and show that methoxylation of the parent flavone structure
      at position 4' confers parthanatos-inhibiting activity while additional
      methoxylation at position 3', reported by others to improve metabolic stability,
      does not destroy the activity. These molecules may therefore serve as leads for
      the development of novel neurotherapeutics for the management of neurological and
      neurodegenerative conditions.

PMID- 23550803
TI  - The perceived importance and the presence of creative potential in the health
      professional's work environment.
AB  - The value of creative employees to an organisation's growth and innovative
      development, productivity, quality and sustainability is well established. This
      study examined the perceived relationship between creativity and work environment
      factors of 361 practicing health professionals, and whether these factors were
      present (realised) in their work environment. Job design (challenges, team work,
      task rotation, autonomy) and leadership (coaching supervisor, time for thinking,
      creative goals, recognition and incentives for creative ideas and results) were
      perceived as the most important factors for stimulating creativity. There was
      room for improvement of these in the work environment. Many aspects of the
      physical work environment were less important. Public health sector employers and
      organisations should adopt sustainable strategies which target the important work
      environment factors to support employee creativity and so enhance service
      quality, productivity, performance and growth. Implications of the results for
      ergonomists and workplace managers are discussed with a participatory ergonomics
      approach recommended. PRACTITIONER SUMMARY: Creative employees are important to
      an organisation's innovation, productivity and sustainability. The survey
      identified health professionals perceive a need to improve job design and
      leadership factors at work to enhance and support employee creativity. There are
      implications for organisations and ergonomists to investigate the creative
      potential of work environments.

PMID- 23550804
TI  - Helicity-selective photoreaction of single-walled carbon nanotubes with
      organosulfur compounds in the presence of oxygen.
AB  - This report describes a helicity-selective photoreaction of single-walled carbon
      nanotubes (SWNTs) with disulfide in the presence of oxygen. The SWNTs were
      characterized using absorption, photoluminescence (PL), Raman, and X-ray
      photoelectron spectroscopy, scanning electron microscopy, and current-voltage (I
      V) measurements. Results showed remarkable helicity-selective (metallic
      SWNTs/semiconducting SWNTs and diameter) functionalization of SWNTs. The reaction
      rate decreases in the order of metallic SWNTs > semiconducting SWNTs and small
      diameter SWNTs > large-diameter SWNTs. Control experiments conducted under
      various experimental conditions and ESR and femtosecond laser flash photolysis
      measurements revealed that the helicity-selective reaction proceeds via a
      photoinduced electron transfer reaction. The PL and I-V measurements showed that
      the photoreaction is effective not only to control SWNT conductivity but also for
      the band gap modulation of semiconducting SWNTs.

PMID- 23550805
TI  - Human versus animal: contrasting decomposition dynamics of mammalian analogues in
      experimental taphonomy.
AB  - Taphonomic studies regularly employ animal analogues for human decomposition due
      to ethical restrictions relating to the use of human tissue. However, the
      validity of using animal analogues in soil decomposition studies is still
      questioned. This study compared the decomposition of skeletal muscle tissues
      (SMTs) from human (Homo sapiens), pork (Sus scrofa), beef (Bos taurus), and lamb
      (Ovis aries) interred in soil microcosms. Fixed interval samples were collected
      from the SMT for microbial activity and mass tissue loss determination; samples
      were also taken from the underlying soil for pH, electrical conductivity, and
      nutrient (potassium, phosphate, ammonium, and nitrate) analysis. The overall
      patterns of nutrient fluxes and chemical changes in nonhuman SMT and the
      underlying soil followed that of human SMT. Ovine tissue was the most similar to
      human tissue in many of the measured parameters. Although no single analogue was
      a precise predictor of human decomposition in soil, all models offered close
      approximations in decomposition dynamics.

PMID- 23550806
TI  - Cyclic adenosine monophosphate and brain-derived neurotrophic factor decreased
      oxidative stress and apoptosis in developing hypothalamic neuronal cells: role of
      microglia.
AB  - BACKGROUND: We have previously shown that ethanol (EtOH) increases cellular
      apoptosis to developing neurons via the effects on oxidative stress of neurons
      directly and via increasing production of microglia-derived factors. To study
      further the mechanism of EtOH action on neuronal apoptosis, we determined the
      effects of 2 well-known PKA activators, dibutyryl cAMP (dbcAMP) and brain-derived
      neurotrophic factor (BDNF), on EtOH-activated oxidative stress and apoptotic
      processes in the hypothalamic neurons in the presence and absence of microglial
      cells' influence. METHODS: In enriched neuronal cells from fetal rat hypothalami
      treated with EtOH or with conditioned medium from EtOH-treated microglia, we
      measured cellular apoptosis by the free nucleosome assay and the levels of cAMP,
      BDNF, O2-, reactive oxygen species (ROS), nitrite, glutathione (GSH), and
      catalase following treatment with EtOH or EtOH-treated microglial culture
      conditioned medium. Additionally, we tested the effectiveness of dbcAMP and BDNF
      in preventing EtOH or EtOH-treated microglial conditioned medium on cellular
      apoptosis and oxidative stress in enriched hypothalamic neuronal cell in primary
      cultures. RESULTS: Neuronal cell cultures following treatment with EtOH or EtOH
      activated microglial conditioned medium showed decreased production levels of
      cAMP and BDNF. EtOH also increased apoptotic death as well as oxidative status,
      as demonstrated by higher cellular levels of oxidants but lower levels of
      antioxidants, in neuronal cells. These effects of EtOH on oxidative stress and
      cell death were enhanced by the presence of microglia. Treatment with BDNF or
      dbcAMP decreased EtOH or EtOH-activated microglial conditioned medium-induced
      changes in the levels of intracellular free radicals, ROS and O2-, nitrite, GSH,
      and catalase. CONCLUSIONS: These data support the possibility that EtOH by acting
      directly and via increasing the production of microglial-derived factors reduces
      cellular levels of cAMP and BDNF to increase cellular oxidative status and
      apoptosis in hypothalamic neuronal cells in primary cultures.

PMID- 23550807
TI  - The HI-STAR study: resource utilization and costs associated with serologic
      testing for antibody-positive patients at four United States medical centers.
AB  - BACKGROUND: Little is known about how the resource utilization and costs of
      serologic work ups for positive antibody screens vary across subpopulations based
      on diagnosis, transfusion history, and serologic testing history. STUDY DESIGN
      AND METHODS: Detailed data were collected on patient demographics, diagnoses,
      transfusion history, history of known allo- and autoantibodies, and specific
      serologic tests performed for 6077 consecutive serologic work ups in 3608
      antibody-positive patients between 2009 and 2011 at four US academic medical
      centers. Direct testing costs were also determined at each site for each
      serologic test performed to calculate total costs per work up and per patient
      over the duration of the study. RESULTS: The mean direct cost of serologic
      testing was $114 per work up and $195 per patient. The mean cost per patient was
      significantly higher for 12 of 19 diagnostic categories evaluated, including
      autoimmune hemolytic anemia (mean cost per patient, $1490; p < 0.001),
      hematologic malignancies ($640, p < 0.001), and transplant recipients ($462, p =
      0.019). Patient transfusion and serologic testing characteristics associated with
      greatest increases in costs included history of a warm autoantibody ($626, p <
      0.001) and more than five prior transfusions ($404, p < 0.001). CONCLUSION:
      Antibody-positive patients with complex diagnoses or transfusion histories
      require significantly more resources and incur greater cost to assess red blood
      cell antibody status.

PMID- 23550808
TI  - The bioequivalence of the contraceptive steroids ethinylestradiol and
      drospirenone is not affected by co-administration of dehydroepiandrosterone.
AB  - OBJECTIVES: To study the effect of co-administration of 50 mg
      dehydroepiandrosterone (DHEA) on the bioequivalence of ethinylestradiol (EE) and
      drospirenone (DRSP) in women who were using a combined oral contraceptive (COC)
      containing 30 MUg EE and 3 mg DRSP, and to estimate whether the addition of DHEA
      to this COC affects the serum levels and the bioequivalence of the synthetic
      contraceptive steroids. METHODS: This was a randomised, double-blind, two-period
      crossover study. Participants received two EE/DRSP COC treatment cycles in random
      order, one with and one without daily 50 mg DHEA , separated by a 28-day wash-out
      cycle during which the subjects used an EE/levonorgestrel (LNG) COC without DHEA.
      Serum levels of EE and DRSP were measured according to a sampling scheme allowing
      pharmacokinetic evaluations. RESULTS: Addition of DHEA to an EE/DRSP COC had no
      effect on serum levels of EE and DRSP. The COC regimens with and without DHEA
      were bioequivalent. Oestradiol levels were equally suppressed during pill intake,
      whether with placebo or DHEA. CONCLUSION: Adding DHEA to a COC containing EE and
      DRSP does not affect the pharmacokinetic properties of EE and DRSP. Therefore, it
      will most likely not affect its contraceptive efficacy.

PMID- 23550809
TI  - Effect of anaesthetic technique on mortality following major lower extremity
      amputation: a propensity score-matched observational study.
AB  - We investigated whether the type of anaesthesia affects mortality and length of
      stay after non-traumatic major lower extremity amputations. A total of 1365
      eligible patients who were operated on between 2002 and 2010 were included in the
      final analysis. Propensity score matching was used to produce 475 matched pairs
      of patients undergoing operation with either general or regional anaesthesia. We
      found that 30-day mortality was significantly greater in the general anaesthesia
      group compared with the regional anaesthesia group, with an odds ratio (95% CI)
      of 1.5 (1.0-2.3) in the total matched population and 4.2 (1.3-13.4) in a high
      risk subgroup. The median (IQR [range]) length of postoperative hospital stay was
      significantly less in the patients of the high-risk subgroup who had general
      anaesthesia at 15 (7-21 [1-101]) days compared with 25 days (10-37 [0-78]) for
      those who had regional anaesthesia (p = 0.027). The results of our study suggest
      that 30-day mortality is significantly higher in patients undergoing major lower
      extremity amputations under general anaesthesia compared with regional
      anaesthesia.

PMID- 23550810
TI  - Economic evaluation of sevelamer for the treatment of hyperphosphatemia in
      chronic kidney disease patients not on dialysis in the United Kingdom.
AB  - OBJECTIVES: To determine the cost effectiveness of sevelamer vs calcium carbonate
      in patients with chronic kidney disease and not on dialysis (CKD-ND) from the
      perspective of the National Health Service (NHS) in the UK. METHODS: A Markov
      decision analytic model was developed to estimate (1) total life years (LYs),
      quality-adjusted life years (QALYs), and costs for patients treated with
      sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and
      per QALY gained for sevelamer vs calcium carbonate. Data informing probability
      transitions to all-cause death and dialysis inception in CKD-ND patients were
      taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3
      year clinical trial using Weibull regression analysis. Estimates of health
      utility and costs (in L2011) were derived from the published literature. RESULTS:
      Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and
      1.56 QALYs per patient, an increase of L37,282 in total costs per patient vs
      calcium carbonate (3.5% discount), and a per-patient cost of L18,193/LYG and
      L23,878/QALY gained. Results were robust to alternative assumptions in key
      parameters; results were most sensitive to alternative assumptions regarding the
      mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of
      dialysis, and health utility estimates. The probabilistic sensitivity analysis
      showed that sevelamer was cost-effective vs calcium carbonate in 93% of
      simulations at a willingness-to-pay threshold of L30,000/QALY gained.
      LIMITATIONS: While the model simulated a real-world clinical setting, this
      analysis was subject to limitations common to all decision analytic models, in
      that it used a mix of data sources and relied on several assumptions. Not all
      variables that impact real-world outcomes and costs were included in this model.
      CONCLUSIONS: Sevelamer is a cost-effective option compared to calcium carbonate
      for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.

PMID- 23550811
TI  - Central nervous system infections and stroke -- a population-based analysis.
AB  - BACKGROUND: Chronic central nervous system (CNS) infections have been found to
      associate with cerebrovascular complications. Acute CNS infections are more
      common than chronic CNS infections, but whether they could increase the risk of
      vascular diseases has not been studied. METHODS: The study cohort comprised all
      adult patients with diagnoses of CNS infections from Taiwan National Health
      Insurance Research Database during 2000-2009 (n = 533). The comparison group were
      matched by age, sex, urbanization, diagnostic year, and vascular risk factors of
      cases (cases and controls = 1:5). Patients were tracked for at least 1 year.
      Kaplan-Meier analysis was used to compare the risk of stroke and acute myocardial
      infarction (AMI) after adjusting censoring subjects. RESULTS: After adjusting the
      patients demographic characteristics and comorbidities, the risk of patients with
      CNS infections developing stroke was 2.75-3.44 times greater than their
      comparison group. More than 70% of the stroke events were occurring within 1 year
      after CNS infections. The risk of AMI was not found as we compared patients with
      and without CNS infections. CONCLUSIONS: The population-based cohort study
      suggested that adult patients with CNS infections have higher risk to develop
      stroke but not AMI, and the risk is marked within a year after infections.

PMID- 23550812
TI  - Measurement of aggressive behaviors in dementia: comparison of the physical
      aggression subscales of the Cohen-Mansfield Agitation Inventory and the Ryden
      Aggression Scale.
AB  - One of the central issues in the development of research-based interventions for
      aggressive behavior (AB) in late-stage dementia is the provision of precise
      measurement of the major dependent variable, in this case, AB levels. To advance
      the nursing goal of evidence-based practice, this article presents the
      characteristics of two research instruments: the Cohen-Mansfield Agitation
      Inventory (CMAI) aggressive behavior subscale (CMAI-ABS) and the Ryden Aggression
      Scale (RAS) physically aggressive behavior subscale (RAS-PABS). A total of 282
      shower bath events (which are most associated with AB) were observed for 107
      nursing home residents with dementia in nine randomly selected nursing homes.
      Then, we compared the psychometric properties of the CMAI-ABS and the RAS-PABS.
      Moderate to substantial agreements between the two instruments were identified
      using Cohen's Kappa. A similar percentage of AB was found on both subscales.
      Similar items on both subscales, such as hitting and pushing, were moderately
      correlated. Overall, the study results support that the CMAI-ABS and RAS-PABS
      measure a single but multifaceted construct-physically aggressive behavior in
      dementia.

PMID- 23550813
TI  - Cerebellar glioblastoma multiforme: a retrospective study of 28 patients at a
      single institution.
AB  - Cerebellar glioblastoma multiforme (CGBM) is rare and its treatment is ill
      defined. To elucidate prognostic factors, we performed a single institutional
      review of the largest series to date of CGBM. The West China Hospital database
      was reviewed from 2007 to June 2011, and a total of 28 CGBM patients were
      collected. Median age of patients was 50 years old, whereas median Karnofsky
      Performance Status was 80 (range, 30-100). Brainstem invasion was observed in 9
      patients. Sixteen patients received total resection and 12 patients received
      subtotal resection. Postoperative Gamma Knife radiosurgery (GKRS) was
      administered to 22 patients. After operation, 16 patients received concurrent
      GKRS and chemotherapy, and 6 patients received chemotherapy after GKRS. In
      addition, 4 patients only received chemotherapy, and 2 patients did not receive
      either GKRS or chemotherapy due to various reasons. Median follow-up period was
      13.7 months (range, 5.2-28.1 months). Median overall survival (OS) of 28 patients
      was 14.3 months and median progression-free survival (PFS) was 9.4 months.
      Univariate log-rank analysis showed that OS and PFS were significantly related to
      brainstem invasion (p = 0.03, p = 0.04, respectively), extent of resection (p =
      0.02, p = 0.04, respectively) and GKRS (p = 0.01, p = 0.02, respectively) of GBM.
      Multivariate analysis revealed that OS and PFS were also significantly associated
      with brainstem invasion (p = 0.007, p = 0.014, respectively), extent of resection
      (p = 0.032, p = 0.045, respectively) and GKRS (p = 0.031, p = 0.046,
      respectively) of CGBM. According to our study, brainstem invasion, extent of
      resection and GKRS were major prognostic factors for survival. Combination of
      postoperative GKRS and chemotherapy had an improved prognosis, and it may be a
      feasible postoperative adjuvant treatment of CGBM.

PMID- 23550814
TI  - Application of the STOPP/START criteria: a systematic review of the prevalence of
      potentially inappropriate prescribing in older adults, and evidence of clinical,
      humanistic and economic impact.
AB  - WHAT IS KNOWN AND OBJECTIVE: Potentially inappropriate prescribing (PIP) has
      significant clinical, humanistic and economic impacts. Identifying PIP in older
      adults may reduce their burden of adverse drug events. Tools with explicit
      criteria are being developed to screen for PIP in this population. These tools
      vary in their ability to identify PIP in specific care settings and jurisdictions
      due to such factors as local prescribing practices and formularies. One promising
      set of screening tools are the STOPP (Screening Tool of Older Person's
      potentially inappropriate Prescriptions) and START (Screening Tool of Alert
      doctors to the Right Treatment) criteria. We conducted a systematic review of
      research studies that describe the application of the STOPP/START criteria and
      examined the evidence of the impact of STOPP/START on clinical, humanistic and
      economic outcomes in older adults. METHODS: We performed a systematic review of
      studies from relevant biomedical databases and grey literature sources published
      from January 2007 to January 2012. We searched citation and reference lists and
      contacted content experts to identify additional studies. Two authors
      independently selected studies using a predefined protocol. We did not restrict
      selection to particular study designs; however, non-English studies were excluded
      during the selection process. Independent extraction of articles by two authors
      used predefined data fields. For randomized controlled trials and observational
      studies comparing STOPP/START to other explicit criteria, we assessed risk of
      bias using an adapted tool. RESULTS AND DISCUSSION: We included 13 studies: a
      single randomized controlled trial and 12 observational studies. We performed a
      descriptive analysis as heterogeneity of study populations, interventions and
      study design precluded meta-analysis. All observational studies reported the
      prevalence of PIP; however, the application of the criteria was not consistent
      across all studies. Seven of the observational studies compared STOPP/START with
      other explicit criteria. The STOPP/START criteria were reported to be more
      sensitive than the more-frequently-cited Beers criteria in six studies, but less
      sensitive than a set of criteria developed in Australia. The STOPP criteria
      identified more medications associated with adverse drug events than the 2002
      version of the Beers criteria. Patients with PIP, as identified by STOPP, had an
      85% increased risk of adverse drug events in one study (OR = 1.85, 95% CI: 1.51
      2.26; P < 0.001). There was limited evidence that the application of STOPP/START
      criteria optimized prescribing. Research involving the application of STOPP/START
      on the impact on the quality of life was not found. The direct costs of PIP were
      documented in three studies from Ireland, but more extensive analyses on the
      economic impact or studies from other jurisdictions were not found. WHAT IS NEW
      AND CONCLUSION: The STOPP/START criteria have been used to review the medication
      profiles of community-dwelling, acute care and long-term care older patients in
      Europe, Asia and North America. Observational studies have reported the
      prevalence and predictors of PIP. The STOPP/START criteria appear to be more
      sensitive than the 2002 version of the Beers criteria. Limited evidence was found
      related to the clinical and economic impact of the STOPP/START criteria.

PMID- 23550815
TI  - Designing a polycationic probe for simultaneous enrichment and detection of
      microRNAs in a nanopore.
AB  - The nanopore sensor can detect cancer-derived nucleic acid biomarkers such as
      microRNAs (miRNAs), providing a noninvasive tool potentially useful in medical
      diagnostics. However, the nanopore-based detection of these biomarkers remains
      confounded by the presence of numerous other nucleic acid species found in
      biofluid extracts. Their nonspecific interactions with the nanopore inevitably
      contaminate the target signals, reducing the detection accuracy. Here we report a
      novel method that utilizes a polycationic peptide-PNA probe as the carrier for
      selective miRNA detection in the nucleic acid mixture. The cationic probe
      hybridized with microRNA forms a dipole complex, which can be captured by the
      pore using a voltage polarity that is opposite the polarity used to capture
      negatively charged nucleic acids. As a result, nontarget species are driven away
      from the pore opening, and the target miRNA can be detected accurately without
      interference. In addition, we demonstrate that the PNA probe enables accurate
      discrimination of miRNAs with single-nucleotide difference. This highly sensitive
      and selective nanodielectrophoresis approach can be applied to the detection of
      clinically relevant nucleic acid fragments in complex samples.

PMID- 23550816
TI  - The sleeper effect of intimate partner violence exposure: long-term consequences
      on young children's aggressive behavior.
AB  - BACKGROUND: Children who have been exposed to intimate partner violence (IPV)
      experience a wide variety of short-term social adjustment and emotional
      difficulties, including externalizing behavioral problems such as aggression.
      While children are affected by IPV at all ages, little is known about the long
      term consequences of IPV exposure at younger ages. Because early experiences
      provide the foundation for later development, children exposed to IPV as an
      infant or toddler may experience worse negative outcomes over time than children
      never exposed. METHODS: Using the National Survey of Child and Adolescent Well
      Being (NSCAW), latent growth curve modeling was conducted to examine whether
      early IPV exposure occurring between birth and age three (n = 107), compared with
      no exposure (n = 339), affects the development of aggressive behavior over 5
      years. This modeling allowed for empirical exploration of developmental
      trajectories, and considered whether initial social development trajectories and
      change over time vary according to early IPV exposure. RESULTS: Children who were
      exposed to more frequent early IPV did not have significantly different
      aggressive behavior problems initially than children who were never exposed.
      However, over time, the more frequently children were exposed between birth and 3
      years, the more aggressive behavior problems were exhibited by age eight.
      CONCLUSIONS: Results indicate a long-term negative behavioral effect on children
      who have been exposed to IPV at an early age. An initial assessment directly
      following exposure to IPV may not be able to identify behavior problems in young
      children. Because the negative effects of early IPV exposure are delayed until
      the child is of school age, early intervention is necessary for reducing the risk
      of later aggressive behavior.

PMID- 23550817
TI  - A short, organocatalytic formal synthesis of (-)-swainsonine and related
      alkaloids.
AB  - A short synthesis of hydroxyalkyl dihydropyrroles has been developed that
      involves the coupling of propargylamines with alpha-chloroaldehydes, followed by
      Lindlar reduction and a one-pot epoxide formation/opening sequence. The
      application of this process to the synthesis of unnatural iminosugars and a
      formal synthesis of (-)-swainsonine is described.

PMID- 23550818
TI  - Interconversion of chromium species during air sampling: effects of O3, NO2, SO2,
      particle matrices, temperature, and humidity.
AB  - The interconversion between Cr(VI), a pulmonary carcinogen, and Cr(III), an
      essential human nutrient, poses challenges to the measurement of Cr(VI) in
      airborne particles. Chamber and field tests were conducted to identify the
      factors affecting Cr(VI)-Cr(III) interconversion in the basic filter medium under
      typical sampling conditions. In the chamber tests, isotopically enriched
      (53)Cr(VI) and (50)Cr(III) were spiked on diesel particulate matter (DPM) and
      secondary organic aerosol (SOA) that were precollected on a basic MCE filter. The
      filter samples were then exposed to clean air or the air containing SO2 (50 and
      160 ppb), 100 ppb O3, or 150 ppb NO2 for 24 h at 16.7 LPM flow rate at designated
      temperature (20 and 31  degrees C) and RH (40% and 70%) conditions. Exposure to
      160 ppb SO2 had the greatest effect on (53)Cr(VI) reduction, with (53)Cr(VI)
      recovery of 31.7 +/- 15.8% (DPM) and 42.0 +/- 7.9% (SOA). DPM and SOA matrix
      induced (53)Cr(VI) reduction when exposed to clean air while reactive oxygen
      species in SOA could promote (50)Cr(III) oxidation. Deliquescence when RH
      increased from 40% to 70% led to conversion of Cr(III) in SOA, whereas oxidized
      organics in DPM and SOA enhanced hygroscopicity and thus facilitated Cr(VI)
      reduction. Field tests showed seasonal variation of Cr(VI)-Cr(III)
      interconversion during sampling. Correction of the interconversion using USEPA
      method 6800 is recommended to improve accuracy of ambient Cr(VI) measurements.

PMID- 23550819
TI  - Variability in bacteria and virus-like particle abundances during purging of
      unconfined aquifers.
AB  - Standard methodologies for sampling the physicochemical conditions of groundwater
      recommend purging a bore for three bore volumes to avoid sampling the stagnant
      water within a bore and instead gain samples representative of the aquifer.
      However, there are currently no methodological standards addressing the amount of
      purging required to gain representative biological samples to assess groundwater
      bacterial and viral abundances. The objective of this study was to examine how
      bacterial and viral abundances change during the purging of bore volumes. Six
      bores infiltrating into unconfined aquifers were pumped for five or six bore
      volumes each and bacteria and virus-like particles (VLPs) were enumerated from
      each bore volume using flow cytometry. In examination of the individual bores
      trends in bacterial abundances were observed to increase, decrease, or remain
      constant with each purged bore volume. Furthermore, triplicates taken at each
      bore volume indicated substantial variations in VLP and bacterial abundances that
      are often larger than the differences between bore volumes. This indicates a high
      level of small scale heterogeneity in microbial community abundance in
      groundwater samples, and we suggest that this may be an intrinsic feature of bore
      biology. The heterogeneity observed may be driven by bottom up processes
      (variability in the distribution of organic and inorganic nutrients), top-down
      processes (grazing and viral lysis), physical heterogeneities in the bore, or
      technical artifacts associated with the purging process. We suggest that a more
      detailed understanding of the ecology underpinning this variability is required
      to adequately describe the microbiological characteristics of groundwater
      ecosystems. 

PMID- 23550820
TI  - Evaporation-induced buckling and fission of microscale droplet interface
      bilayers.
AB  - Droplet interface bilayers (DIBs) are a robust platform for studying synthetic
      cellular membranes; however, to date no DIBs have been produced at cellular
      length scales. Here, we create microscale droplet interface bilayers (MUDIBs) at
      the interface between aqueous femtoliter-volume droplets within an oil-filled
      microfluidic channel. The uniquely large area-to-volume ratio of the droplets
      results in strong evaporation effects, causing the system to transition through
      three distinct regimes. First, the two adjacent droplets shrink into the shape of
      a single spherical droplet, where an augmented lipid bilayer partitions two
      hemispherical volumes. In the second regime, the combined effects of the
      shrinking monolayers and growing bilayer force the confined bilayer to buckle to
      conserve its mass. Finally, at a critical bending moment, the buckling bilayer
      fissions a vesicle to regulate its shape and mass. The MUDIBs produced here
      enable evaporation-induced bilayer dynamics reminiscent of endo- and exocytosis
      in cells.

PMID- 23550821
TI  - Intraperitoneal injection of ethanol results in drastic changes in bone
      metabolism not observed when ethanol is administered by oral gavage.
AB  - BACKGROUND: Chronic alcohol abuse is associated with increased risk of
      osteoporosis while light-to-moderate alcohol intake correlates with reduced
      osteoporosis risk. Addition of alcohol to a liquid diet is often used to model
      chronic alcohol abuse. Methods to model intermittent drinking (including binge
      drinking and light-to-moderate consumption) include (i) intragastric
      administration of alcohol by oral gavage or (ii) intraperitoneal (ip)
      administration of alcohol by injection. However, it is unclear whether the latter
      2 methods produce comparable results. The purpose of this investigation was to
      determine the skeletal response to alcohol delivered daily by oral gavage or ip
      injection. METHODS: Ethanol (EtOH) or vehicle was administered to 4-month-old
      female Sprague-Dawley rats once daily at 1.2 g/kg body weight for 7 days.
      Following necropsy, bone formation and bone architecture were evaluated in tibial
      diaphysis (cortical bone) and proximal tibial metaphysis (cancellous bone) by
      histomorphometry. mRNA was measured for bone matrix proteins in distal femur
      metaphysis. RESULTS: Administration of alcohol by gavage had no significant
      effect on body weight gain or bone measurements. In contrast, administration of
      the same dose of alcohol by ip injection resulted in reduced body weight, total
      suppression of periosteal bone formation in tibial diaphysis, decreased
      cancellous bone formation in proximal tibial metaphysis, and decreased mRNA
      levels for bone matrix proteins in distal femur. CONCLUSIONS: Our findings raise
      concerns regarding the use of ip injection of EtOH in rodents as a method for
      modeling the skeletal effects of intermittent exposure to alcohol in humans. This
      concern is based on a failure of the ip route to replicate the oral route of
      alcohol administration.

PMID- 23550822
TI  - School life and adolescents' self-esteem trajectories.
AB  - This study investigates heterogeneity in adolescents' trajectories of global self
      esteem (GSE) and the relations between these trajectories and facets of the
      interpersonal, organizational, and instructional components of students' school
      life. Methodologically, this study illustrates the use of growth mixture
      analyses, and how to obtain proper student-level effects when there are multiple
      schools, but not enough to support multilevel analyses. This study is based on a
      4-year, six-measurement-point, follow-up of 1,008 adolescents (M(age) = 12.6
      years, SD = 0.6 at Time 1.) The results show four latent classes presenting
      elevated, moderate, increasing, and low trajectories defined based on GSE levels
      and fluctuations. The results show that GSE becomes trait-like as it increases
      and that school life effects, moderated by gender, played an important role in
      predicting membership in these trajectories.

PMID- 23550824
TI  - A brief introduction to human factors engineering.

PMID- 23550825
TI  - Step scaling and behaviour selection in a constrained set of manual material
      handling transfers.
AB  - Predictive biomechanical analysis of manual material handling (MMH) transfers is
      dependent on accurate prediction of foot locations relative to the task. Previous
      studies have classified common acyclic stepping patterns used during those
      transfer tasks, but the influence of walking distance prior to the transfer is
      not well understood. Twenty men and women performed transfers for a minimum of
      six different delivery distance conditions. The number of steps used by the
      participants ranged from two to seven. A theoretical framework for idealised step
      scaling strategies is proposed and compared with the experimental data. The
      maximum observed increase in step length prior to delivery was 1.43 times the
      nominal step length calculated for each participant. The data suggest that
      although participants can scale their steps to facilitate the use of a single
      terminal stance at the transfer, the majority of participants chose to utilise a
      combination of stepping strategies if the preferred contralateral lead foot
      strategy could not be easily implemented. PRACTITIONER SUMMARY: Accurate foot
      placements are needed for predictive biomechanical analysis of MMH. A laboratory
      study investigated the influence of previous step positions on MMH. A flexible
      step-scaling strategy, in which step lengths and strategy were varied, suggests
      that analysis based on simulated movements should consider multiple lifting
      postures.

PMID- 23550826
TI  - Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the
      colostomy site after abdominoperineal resection for rectal carcinoma.
AB  - The occurrence of a tumor at the colostomy site after abdominoperineal resection
      for rectal carcinoma is rare and it may be related to a previously resected
      carcinoma or another primary tumor. We report a 61-year-old man who developed an
      ulcerated skin nodule at her colostomy site 6 years after resection of a rectal
      adenocarcinoma. Histopathologically, the skin nodule was composed of atypical
      large and pleomorphic cells with high mitotic rate and they were arranged in
      nests and within lymphatic channels in the dermis. The neoplastic cells were
      immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34betaE12, epithelial membrane
      antigen and vimentin while detection of human papillomavirus and Epstein-Barr
      virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary
      origin was suggested and it was confirmed by computed tomography-guided fine
      needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy
      site is an exceptional finding and may be the first manifestation of lung cancer,
      especially if it consist of pleomorphic large cells with high mitotic rate and
      basaloid immunophenotype.

PMID- 23550823
TI  - Quantifying the metabolic activities of human-associated microbial communities
      across multiple ecological scales.
AB  - Humans are home to complex microbial communities, whose aggregate genomes and
      their encoded metabolic activities are referred to as the human microbiome.
      Recently, researchers have begun to appreciate that different human body habitats
      and the activities of their resident microorganisms can be better understood in
      ecological terms, as a range of spatial scales encompassing single cells, guilds
      of microorganisms responsive to a similar substrate, microbial communities, body
      habitats, and host populations. However, the bulk of the work to date has focused
      on studies of culturable microorganisms in isolation or on DNA sequencing-based
      surveys of microbial diversity in small-to-moderate-sized cohorts of individuals.
      Here, we discuss recent work that highlights the potential for assessing the
      human microbiome at a range of spatial scales, and for developing novel
      techniques that bridge multiple levels: for example, through the combination of
      single-cell methods and metagenomic sequencing. These studies promise to not only
      provide a much-needed epidemiological and ecological context for mechanistic
      studies of culturable and genetically tractable microorganisms, but may also lead
      to the discovery of fundamental rules that govern the assembly and function of
      host-associated microbial communities. 

PMID- 23550827
TI  - Analysis of bone healing in a postoperative patient: skeletal evidence of medical
      neglect and human rights violations.
AB  - This study highlights complexities associated with postsurgical trauma
      interpretation of a 76-year-old female patient from a psychiatric institution in
      Mexico. The skeletal analysis identified complications from an unsuccessful
      surgical operation for an intertrochanteric fracture of the femur. An improperly
      placed surgical plate resulted in nonunion due to limited contact between
      fracture margins. However, it is unclear whether this resulted from surgical
      complications, ineffective postoperative care, or from the decedent's limited
      ability to follow postoperative care instructions. Additionally, failure of the
      plate resulted in degenerative changes to the acetabulum. These complications,
      associated with degenerative changes to upper limb joints, suggest significant
      mobility issues. The pattern of antemortem trauma and contextual information
      support a conclusion of postoperative medical neglect, a documented problem in
      psychiatric institutions in Latin America. This study provides insight into the
      relevance of detailed trauma assessment of skeletal remains in cases where
      neglect and human rights violations are suspected. 

PMID- 23550828
TI  - The influence of maternal disease on metabolites measured as part of newborn
      screening.
AB  - OBJECTIVE: Measurements of neonatal metabolites are commonly used in newborn
      screening (NBS) programs to detect inborn errors of metabolism. Variation in
      these metabolites, particularly in infants born preterm (<37 weeks gestation),
      can result from multiple etiologies. We sought to evaluate the impact of maternal
      complications of pregnancy and environmental stressors on NBS metabolites.
      METHODS: We examined 49 metabolic biomarkers obtained from routine NBS in 452
      infants born preterm for association with maternal environmental stressors and
      complications of pregnancy. RESULTS: Neonatal free carnitine (C0, p = 1.4 * 10(
      7)), acetylcarnitine (C2, p = 2.7 * 10(-7)), octenoylcarnitine (C8:1, p = 5.2 *
      10(-11)) and linoleoylcarnitine (C18:2, p = 9.1 * 10(-7)) were elevated in
      infants born to preeclamptic mothers. Similar elevations were observed in small
      for gestational age infants and in infants where labor was not initiated prior to
      delivery. When accounting for all three factors, associations remained strongest
      between acylcarnitines and preeclampsia. CONCLUSION: We observed that maternal
      conditions, particularly preeclampsia, influence NBS biomarkers. This is
      important for identifying maternal conditions that influence metabolites measured
      during routine NBS that are also markers of fetal growth and overall health.

PMID- 23550830
TI  - Tandem ring-closing metathesis/isomerization reactions for the total synthesis of
      violacein.
AB  - A series of 5-substituted 2-pyrrolidinones was synthesized through a one-pot
      ruthenium alkylidene-catalyzed tandem RCM/isomerization/nucleophilic addition
      sequence. The intermediates resulting from RCM/isomerization showed reactivity
      toward electrophiles in aldol condensation reactions which provided a new entry
      for the total synthesis of the antileukemic natural product violacein.

PMID- 23550829
TI  - The unconventional P-loop NTPase OsYchF1 and its regulator OsGAP1 play opposite
      roles in salinity stress tolerance.
AB  - YchF proteins are a group of mysterious but ubiquitous unconventional G-proteins
      found in all kingdoms of life except Archaea. Their functions have been
      documented in microorganisms, protozoa and human, but those of plant YchF
      homologues are largely unknown. Our group has previously shown that OsYchF1 and
      its interacting protein, OsGAP1, play opposite roles in plant defense responses.
      OsGAP1 was found to stimulate the GTPase/ATPase activities of OsYchF1 and
      regulate its subcellular localization. In this report, we demonstrate that both
      OsYchF1 and OsGAP1 are localized mainly in the cytosol under NaCl treatment. The
      ectopic expression of OsYchF1 in transgenic Arabidopsis thaliana leads to reduced
      tolerance towards salinity stress, while the ectopic expression of OsGAP1 has the
      opposite effect. Similar results were also obtained with the Arabidopsis
      homologues, AtYchF1 and AtGAP1, by using AtGAP1 overexpressors and
      underexpressors, as well as an AtYchF1-knockdown mutant. OsYchF1 and OsGAP1 also
      exhibit highly significant effects on salinity-induced oxidative stress
      tolerance. The expression of OsYchF1 suppresses the anti-oxidation enzymatic
      activities and increases lipid peroxidation in transgenic Arabidopsis, and leads
      to the accumulation of reactive oxygen species (ROS) in tobacco BY-2 cells, while
      the ectopic expression of OsGAP1 has the opposite effects in these two model
      systems. 

PMID- 23550831
TI  - Blood pressure management in trauma: from feast to famine?

PMID- 23550832
TI  - Flexible solid-state supercapacitors based on three-dimensional graphene hydrogel
      films.
AB  - Flexible solid-state supercapacitors are of considerable interest as mobile power
      supply for future flexible electronics. Graphene or carbon nanotubes based thin
      films have been used to fabricate flexible solid-state supercapacitors with high
      gravimetric specific capacitances (80-200 F/g), but usually with a rather low
      overall or areal specific capacitance (3-50 mF/cm(2)) due to the ultrasmall
      electrode thickness (typically a few micrometers) and ultralow mass loading,
      which is not desirable for practical applications. Here we report the exploration
      of a three-dimensional (3D) graphene hydrogel for the fabrication of high
      performance solid-state flexible supercapacitors. With a highly interconnected 3D
      network structure, graphene hydrogel exhibits exceptional electrical conductivity
      and mechanical robustness to make it an excellent material for flexible energy
      storage devices. Our studies demonstrate that flexible supercapacitors with a 120
      MUm thick graphene hydrogel thin film can exhibit excellent capacitive
      characteristics, including a high gravimetric specific capacitance of 186 F/g (up
      to 196 F/g for a 42 MUm thick electrode), an unprecedented areal specific
      capacitance of 372 mF/cm(2) (up to 402 mF/cm(2) for a 185 MUm thick electrode),
      low leakage current (10.6 MUA), excellent cycling stability, and extraordinary
      mechanical flexibility. This study demonstrates the exciting potential of 3D
      graphene macrostructures for high-performance flexible energy storage devices.

PMID- 23550833
TI  - An unsteady state tracer method for characterizing fractures in bedrock wells.
AB  - Evaluating contaminants impacting wells in fractured crystalline rock requires
      knowledge of the individual fractures contributing water. This typically involves
      using a sequence of tools including downhole geophysics, flow meters, and
      straddle packers. In conjunction with each other these methods are expensive,
      time consuming, and can be logistically difficult to implement. This study
      demonstrates an unsteady state tracer method as a cost-effective alternative for
      gathering fracture information in wells. The method entails introducing tracer
      dye throughout the well, inducing fracture flow into the well by conducting a
      slug test and then profiling the tracer concentration in the well to locate water
      contributing fractures where the dye has been diluted. By monitoring the
      development of the dilution zones within the wellbore with time, the
      transmissivity and the hydraulic head of the water contributing fractures can be
      determined. Ambient flow conditions and the contaminant concentration within the
      fractures can also be determined from the tracer dilution. This method was tested
      on a large physical model well and a bedrock well. The model well was used to
      test the theory underlying the method and to refine method logistics. The
      approach located the fracture and generated transmissivity values that were in
      excellent agreement with those calculated by slug testing. For the bedrock well
      tested, two major active fractures were located. Fracture location and ambient
      well conditions matched results from conventional methods. Estimates of
      transmissivity values by the tracer method were within an order of magnitude of
      those calculated using heat-pulse flow meter data. 

PMID- 23550834
TI  - Circadian clock period inversely correlates with illness severity in cells from
      patients with alcohol use disorders.
AB  - BACKGROUND: Clinical and genetic studies suggest circadian clock genes may
      contribute to biological mechanisms underlying alcohol use disorders (AUD). In
      particular, the Per2 gene regulates alcohol consumption in mutant animals, and in
      humans with AUD, the 10870 variant in PER2 has been associated with alcohol
      consumption. However, with respect to function, the molecular clock remains
      largely uncharacterized in AUD patients. METHODS: In skin fibroblast cultures
      from well-characterized human AUD patients (n = 19) and controls (n = 13), we
      used a bioluminescent reporter gene (Per2::luc) to measure circadian rhythms in
      gene expression at high sampling density for 5 days. Cells were genotyped for the
      PER2 10870 variant. The rhythm parameters period and amplitude were then analyzed
      using a case-control design and by genetic and clinical characteristics of the
      AUD subjects. RESULTS: There were no differences between AUD cases and controls
      in rhythm parameters. However, period was inversely correlated with illness
      severity (defined as the number of alcohol dependence criteria met). The PER2
      variant 10870 was not associated with differences in rhythm parameters.
      CONCLUSIONS: Our data suggest that differences in the cellular circadian clock
      are not pronounced in fibroblasts from AUD cases and controls. However, we found
      evidence that the circadian clock may be associated with an altered trajectory of
      AUD, possibly related to illness severity. Future work will be required to
      determine the mechanistic basis of this association.

PMID- 23550836
TI  - Differences in the released endothelial microparticle subtypes between human
      pulmonary microvascular endothelial cells and aortic endothelial cells in vitro.
AB  - Circulating endothelial microparticles (EMPs) are membrane vesicles that are shed
      into the blood stream from activated or apoptotic endothelial cells. We
      previously reported that circulating EMP numbers significantly increased in
      stable chronic obstructive pulmonary disease (COPD) patients and during
      exacerbation compared with healthy control subjects. However, different types of
      circulating EMPs with distinct time profiles were detectable during
      exacerbations. We hypothesized that the released EMP subtypes correlated with
      differences in the inflammatory stimuli and the endothelial cell type. We
      compared the EMP subtypes from human aortic endothelial cells (Aortic ECs) and
      human lung microvascular endothelial cells (Pulmonary microvascular ECs) released
      in response to various stimuli, including proinflammatory cytokines (TNFalpha),
      oxidative stress (H2O2), and cigarette smoke extracts (CSE) in vitro. We defined
      circulating EMPs by the expression of endothelial antigens: CD144(+) MPs (VE
      cadherin EMPs), CD31(+)/CD41(-) MPs (PECAM EMPs), CD62E(+) MPs (E-selectin EMPs),
      and CD146(+) MPs (MCAM EMPs). E-selectin EMPs were released from both pulmonary
      microvascular and aortic ECs in response to TNFalpha but not to H2O2 or CSE
      stimulation. The amount of MCAM EMPs released from pulmonary microvascular ECs
      differed significantly between the cells stimulated with H2O2 and those
      stimulated with CSE. VE-cadherin EMPs were only released from aortic ECs, whereas
      PECAM EMPs were released exclusively from pulmonary microvascular ECs. The EMP
      subtypes released differ in vitro among TNFalpha, H2O2, and CSE stimulation as
      well as between pulmonary microvascular and aortic ECs. The differences in
      circulating EMP subtypes may reflect a condition or site of endothelial injury
      and may serve as markers for endothelial damage in COPD patients.

PMID- 23550835
TI  - Up-regulation and activation of the P2Y(2) nucleotide receptor mediate neurite
      extension in IL-1beta-treated mouse primary cortical neurons.
AB  - The pro-inflammatory cytokine interleukin-1beta (IL-1beta), whose levels are
      elevated in the brain in Alzheimer's and other neurodegenerative diseases, has
      been shown to have both detrimental and beneficial effects on disease
      progression. In this article, we demonstrate that incubation of mouse primary
      cortical neurons (mPCNs) with IL-1beta increases the expression of the P2Y2
      nucleotide receptor (P2Y2R) and that activation of the up-regulated receptor with
      UTP, a relatively selective agonist of the P2Y2R, increases neurite outgrowth.
      Consistent with the accepted role of cofilin in the regulation of neurite
      extension, results indicate that incubation of IL-1beta-treated mPCNs with UTP
      increases the phosphorylation of cofilin, a response absent in PCNs isolated from
      P2Y2R(-/-) mice. Other findings indicate that function-blocking anti-alphav
      beta3/5 integrin antibodies prevent UTP-induced cofilin activation in IL-1beta
      treated mPCNs, suggesting that established P2Y2R/alphav beta3/5 interactions that
      promote G12 -dependent Rho activation lead to cofilin phosphorylation involved in
      neurite extension. Cofilin phosphorylation induced by UTP in IL-1beta-treated
      mPCNs is also decreased by inhibitors of Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII), suggesting a role for P2Y2R-mediated and Gq-dependent calcium
      mobilization in neurite outgrowth. Taken together, these studies indicate that up
      regulation of P2Y2Rs in mPCNs under pro-inflammatory conditions can promote
      cofilin-dependent neurite outgrowth, a neuroprotective response that may be a
      novel pharmacological target in the treatment of neurodegenerative diseases.

PMID- 23550837
TI  - Predicting vitamin D deficiency in older Australian adults.
AB  - OBJECTIVE: There has been a dramatic increase in vitamin D testing in Australia
      in recent years, prompting calls for targeted testing. We sought to develop a
      model to identify people most at risk of vitamin D deficiency. DESIGN AND
      PARTICIPANTS: This is a cross-sectional study of 644 60- to 84-year-old
      participants, 95% of whom were Caucasian, who took part in a pilot randomized
      controlled trial of vitamin D supplementation. MEASUREMENTS: Baseline 25(OH)D was
      measured using the Diasorin Liaison platform. Vitamin D insufficiency and
      deficiency were defined using 50 and 25 nmol/l as cut-points, respectively. A
      questionnaire was used to obtain information on demographic characteristics and
      lifestyle factors. We used multivariate logistic regression to predict low
      vitamin D and calculated the net benefit of using the model compared with 'test
      all' and 'test-none' strategies. RESULTS: The mean serum 25(OH)D was 42 (SD 14)
      nmol/1. Seventy-five per cent of participants were vitamin D insufficient and 10%
      deficient. Serum 25(OH)D was positively correlated with time outdoors, physical
      activity, vitamin D intake and ambient UVR, and inversely correlated with age,
      BMI and poor self-reported health status. These predictors explained
      approximately 21% of the variance in serum 25(OH)D. The area under the ROC curve
      predicting vitamin D deficiency was 0.82. Net benefit for the prediction model
      was higher than that for the 'test-all' strategy at all probability thresholds
      and higher than the 'test-none' strategy for probabilities up to 60%. CONCLUSION:
      Our model could predict vitamin D deficiency with reasonable accuracy, but it
      needs to be validated in other populations before being implemented.

PMID- 23550838
TI  - Comparative analysis of triplex nucleic acid test assays in United States blood
      donors.
AB  - BACKGROUND: This study assessed the clinical sensitivity of three fully
      automated, human immunodeficiency virus (HIV), hepatitis C virus (HCV), and
      hepatitis B virus (HBV) triplex nucleic acid test (NAT) assays by individual
      donation (ID-NAT) and at operational minipool (MP-NAT) sizes used worldwide.
      STUDY DESIGN AND METHODS: MPX, Ultrio, and Ultrio Plus were used to test 2222
      pedigreed, marker-positive samples with varying viral loads, each from a unique
      US blood donor. NAT-positive, seronegative yield samples (16 HBV, 156 HCV, and 23
      HIV) were tested in replicates of three; undiluted; and in 1:6, 1:8, and 1:16
      dilutions (MP6, MP8, and MP16), simulating various MP sizes. Seropositive samples
      (1276 HBV, 488 HCV, and 263 HIV) were tested by ID-NAT in singlet. RESULTS: MPX
      MP6 and Ultrio Plus-MP16 had equivalent HCV sensitivity. Although Ultrio Plus
      MP16 for HIV trended toward lesser sensitivity, this was not corroborated in a
      large substudy of low-viral-load samples in which Ultrio Plus-MP8/MP16 showed
      100% reactivity. MPX-ID and Ultrio Plus-ID HBV clinical sensitivity were
      identical, but MPX-MP6 was significantly more sensitive than Ultrio Plus-MP16;
      the differential yield projected to one HBV NAT yield per 4.72 million US
      donations. Ultrio Plus HBV sensitivity did not increase at MP8 versus MP16.
      Ultrio Plus versus Ultrio sensitivity was significantly increased in HBV-infected
      donors with early acute, late acute or chronic, and occult infections. No
      difference in sensitivity was noted for any virus for MPX-MP6 versus Ultrio Plus
      ID. CONCLUSIONS: Our data support US donation screening with MPX-MP6 or Ultrio
      Plus-MP16 since the HBV DNA detection of Ultrio Plus was significantly enhanced
      (vs. Ultrio) without compromising HIV or HCV RNA detection.

PMID- 23550839
TI  - Clinical and biomarker assessment of demyelinating events suggesting multiple
      sclerosis.
AB  - BACKGROUND: Initial demyelinating event (IDE) diagnosis and prognosis are not
      straightforward. OBJECTIVE: To identify potential diagnostic markers and outcome
      predictors of IDEs suggestive of multiple sclerosis (MS), that is, clinically
      isolated syndromes (CISs). METHODS: Clinically isolated syndrome cases (i.e.,
      subjects with an IDE compatible with MS onset and no alternative explanation)
      with at least 1.5 years' follow-up were retrospectively identified. All cases
      underwent clinical, neurophysiological, MRI, and cerebrospinal fluid (CSF)
      assessment, including exploratory tau, 14-3-3, and cystatin C testing. CIS
      recovery, conversion to MS, and long-term neurological disability were used as
      outcome measures. Patients with neuromyelitis optica spectrum disorders,
      idiopathic acute transverse myelitis (IATM), Creutzfeldt-Jacob disease, and non
      inflammatory/non-neurodegenerative disorders served as controls for CSF analysis.
      RESULTS: Forty-six CIS cases were included. Severe presentation was associated
      with incomplete recovery, while presence of at least 3 periventricular lesions on
      baseline MRI correlated with MS conversion. Initial pyramidal tract involvement,
      incomplete CIS recovery, and number of relapses predicted neurological
      disability. CSF tau, 14-3-3, and cystatin C did not correlate with any outcome
      measure. CIS cases had significantly lower tau and cystatin C levels compared to
      IATM. CONCLUSIONS: An extensive diagnostic evaluation of patients with an IDE is
      worthwhile to make prognostic predictions. More robust molecular biomarkers are
      needed.

PMID- 23550840
TI  - Environmental-scale map use in middle childhood: links to spatial skills,
      strategies, and gender.
AB  - Researchers have shown that young children solve mapping tasks in small spaces,
      but have rarely tested children's performance in large, unfamiliar environments.
      In the current research, children (9-10 years; N = 40) explored an unfamiliar
      campus and marked flags' locations on a map. As hypothesized, better performance
      was predicted by higher spatial-test scores, greater spontaneous use of map-space
      coordinating strategies, and participant sex (favoring boys). Data supported some
      but not all hypotheses about the roles of specific spatial skills for mapping
      performance. Data patterns were similar on a computer mapping task that displayed
      environmental-scale videos of walks through a park. Patterns of children's
      mapping errors suggested both idiosyncratic and common mapping strategies that
      should be addressed in future research and educational interventions.

PMID- 23550841
TI  - Bioinspired self-assembled peptide nanofibers with thermostable multivalent alpha
      helices.
AB  - The stabilization of peptide's active conformation is a critical determinant of
      its target binding efficiency. Here we present a structure-based self-assembly
      strategy for the design of nanostructures with multiple and thermostable alpha
      helices using bioinspired peptide amphiphiles. The design principle was inspired
      by the oligomerization of the human immunodeficiency virus type-1 (HIV-1) Rev
      protein. Our goal was to find a strategy to modify the Rev protein into a
      chemically manageable self-assembling peptide while stabilizing its alpha-helical
      structure. Instead of using cyclic peptides for structure stabilization, this
      strategy utilizes the pseudocyclization for helix stabilization. The self
      assembly induced stabilization of alpha-helical conformation could be observed,
      and the alpha-helices were found to be stable even at high temperature (at least
      up to 74  degrees C). Conjugation of a hydrophobic alkyl chain to the Rev peptide
      was crucial for forming the self-assembled nanostructures, and no nanostructures
      could be obtained without this modification. Because chemical modifications to
      the alpha-helical peptide domain can be avoided, potentially any alpha-helical
      peptide fragment can be grafted into this self-assembling peptide scaffold.

PMID- 23550843
TI  - Every picture does not (always) tell a story.

PMID- 23550842
TI  - Microbial succession and metabolite changes during long-term storage of Kimchi.
AB  - Kimchi is often stored for a long period of time for a diet during the winter
      season because it is an essential side dish for Korean meals. In this study pH,
      abundance of bacteria and yeasts, bacterial communities, and metabolites were
      monitored periodically to investigate the fermentation process of kimchi for 120
      d. Bacterial abundance increased quickly with a pH decrease after an initial pH
      increase during the early fermentation period. After 20 d, pH values became
      relatively stable and free sugars were maintained at relatively constant levels,
      indicating that kimchi fermentation by lactic acid bacteria (LAB) was almost
      completed. After that time, a decrease in bacterial abundance and a growth in
      Saccharomyces occurred concurrently with increased free sugar consumption and
      production of glycerol and ethanol. Finally, after 100 d, the growth of Candida
      was observed. Community analysis using pyrosequencing revealed that diverse LAB
      including Leuconostoc citreum, Leuconostoc holzapfelii, Lactococcus lactis, and
      Weissella soli were present during the early fermentation period, but the LAB
      community was quickly replaced with Lactobacillus sakei, Leuconostoc
      gasicomitatum, and Weissella koreensis as the fermentation progressed. Metabolite
      analysis using (1) H-NMR showed that organic acids (lactate, acetate, and
      succinate) as well as bioactive substances (mannitol and gamma-aminobutyric acid
      (GABA)) were produced during the kimchi fermentation, and Leuconostoc strains and
      Lactobacillus sakei were identified as the producers of mannitol and GABA,
      respectively.

PMID- 23550844
TI  - Aerobic biodegradation kinetics and mineralization of six petrodiesel/soybean
      biodiesel blends.
AB  - The aerobic biodegradation kinetics and mineralization of six petrodiesel/soybean
      biodiesel blends (B0, B20, B40, B60, B80, and B100), where B100 is 100%
      biodiesel, were investigated by acclimated cultures. The fatty acid methyl esters
      (FAMEs) of biodiesel were found to undergo rapid abiotic transformation in all
      experiments. The C10-C21 n-alkanes of petrodiesel were metabolized at
      significantly higher microbial utilization rates in the presence of biodiesel.
      The rates of mineralization of the blends were also enhanced in the presence of
      biodiesel; yet a similar enhancement in the extent of mineralization was not
      observed. Abiotic fuel-blends/aqueous-phase equilibration experiments revealed
      that the FAMEs of biodiesel were capable of cosolubilizing the n-alkanes of
      petrodiesel, a mechanism that fully explains the faster utilization and
      mineralization kinetics of petrodiesel in the presence of biodiesel without
      necessarily enhancing the extent of biomineralization. The biodegradation of six
      targeted aromatic compounds present in petrodiesel was also influenced by the
      amount of biodiesel in a blend. While toluene, o-xylene, and tetralin were not
      degraded in the B0 and B20 treatments, all of the targeted aromatic compounds
      were degraded to below detection limits in the B40 and B80 treatments. Biomass
      acclimated to B60, however, was unable to degrade most of the aromatic compounds.
      These results indicate that the amount of biodiesel in a blend significantly
      affects the absolute and relative abundance of the dissolved and bioavailable
      constituents of biodiesel and petrodiesel in a way that can considerably alter
      the biodegrading capacity of microbial cultures.

PMID- 23550845
TI  - A rare combination of sebaceoma with carcinomatous change (sebaceous carcinoma),
      trichoblastoma, and poroma arising from a nevus sebaceus.
AB  - We report a case of a 48-year-old Malay female who presented with multiple tumors
      arising from a large nevus sebaceus on her right parieto-temporal scalp.
      Histologically, the tumors corresponded to a sebaceoma with carcinomatous change,
      a poroma and a trichoblastoma. Immunohistochemical staining of the sebaceous
      tumor with p53 showed strong within the areas of carcinomatous change, while
      there was negative to weak staining within the sebaceoma-like areas. A discussion
      on the potential secondary neoplasms from a nevus sebaceus ensues, with a review
      of this literature on multiple tumors from a nevus sebaceus.

PMID- 23550846
TI  - Efficacy and cost of single-dose rasburicase in prevention and treatment of adult
      tumour lysis syndrome: a meta-analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Single-dose rasburicase for the treatment and
      prevention of hyperuricaemia in adult and paediatric patients with cancer at high
      risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice
      as unlabelled use with limited clinical evidence. This meta-analysis study
      evaluated the efficacy and cost savings of a single-dose rasburicase (SDR)
      regimen compared with the Food and Drug Administration-approved daily dosing of
      rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in
      adult cancer patients with hyperuricaemia or at high risk for TLS. METHODS:
      Prospective and retrospective studies were retrieved from a systemic search of
      major electronic data sources. Studies included in the meta-analysis were those
      with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in
      adult patients with cancer. The results of response rate and controlling of time
      dependent plasma uric acid (UA) reduction were pooled and compared with the
      results from patients treated with DDR for 5 days or patients treated with
      allopurinol. A cost analysis was performed to analyse the treatment costs for
      adults with hyperuricaemia or at high risk for TLS. RESULTS AND DISCUSSION: Ten
      studies (eight retrospective and two prospective) evaluated the SDR response rate
      and plasma UA level reduction over time. The pooled total number of patients
      treated with SDR (from 0.05 mg/kg to 0.20 mg/kg) was 269. The pooled response
      rate of the SDR arm was not significantly different than that of DDR (0.2 mg/kg)
      arm (88.15% vs. 90.18%, P = 0.542), but significantly stronger than that of
      allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88.15% vs. 66%, P
      < 0.0005). Pooled SDR group efficiently controlled the plasma uric acid (UA)
      level below 4.5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA
      levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated
      that standard-dose SDR (>=6 mg) has non-inferior clinical benefit and significant
      cost savings compared with the DDR regimen. WHAT IS NEW AND CONCLUSION: Single
      dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high
      risk for TLS demonstrated better response rate and stronger control of uric acid
      level compared with allopurinol. SDR response rate was not inferior to that of
      DDR, and the standard-dose SDR generates more cost savings compared with the DDR.
      It suggests that the single-dose rasburicase is clinically effective and cost
      efficient for the prophylaxis of high-risk TLS and the treatment of
      hyperuricaemia in adult patients with cancer. Additional randomized control
      studies are needed to confirm the findings of this meta-analysis study.

PMID- 23550847
TI  - Laser technology and applications in gynaecology.
AB  - The term 'laser' is an acronym for Light Amplification by Stimulated Emission of
      Radiation. Lasers are commonly described by the emitted wavelength, which
      determines the colour of the light, as well as the active lasing medium.
      Currently, over 40 types of lasers have been developed with a wide range of both
      industrial and medical uses. Gas and solid-state lasers are frequently used in
      surgical applications, with CO2 and Ar being the most common examples of gas
      lasers, and the Nd:YAG and KTP:YAG being the most common examples of solid-state
      lasers. At present, it appears that the CO2, Nd:YAG, and KTP lasers provide
      alternative methods for achieving similar results, as opposed to superior
      results, when compared with traditional endoscopic techniques, such as cold
      cutting monopolar and bipolar energy. This review focuses on the physics, tissue
      interaction, safety and applications of commonly used lasers in gynaecological
      surgery.

PMID- 23550848
TI  - Uterine transplantation: what else needs to be done before it can become a
      reality?
AB  - Uterine transplantation may be a possible treatment option in the future for
      absolute uterine infertility. We describe three important areas of research that
      we feel are important in order to move closer to a successful and, crucially,
      safe transplant in the human setting. With closer collaboration among the various
      international teams working on this project, the first human uterine transplant
      should be possible in the next few years.

PMID- 23550849
TI  - A review of contemporary modalities for identifying abnormal fetal growth.
AB  - Detecting aberrant fetal growth has long been an important goal of modern
      obstetrics. Failure to diagnose abnormal fetal growth results in perinatal
      morbidity or mortality. However, the erroneous diagnosis of abnormal growth may
      lead to increased maternal anxiety and unnecessary obstetric interventions. We
      review the aetiology of deviant fetal growth and its implications both for the
      neonatal period and later in adult life. We examine maternal factors that may
      influence fetal growth such as obesity, glycaemic control and body composition.
      We discuss novel ways to improve our detection of abnormal fetal growth with a
      view to optimising antenatal care and clinical outcomes. These include using
      customised centiles or individualised growth assessment methods to improve
      accuracy. The role of fetal subcutaneous measurements as a surrogate marker of
      the nutritional status of the baby is also discussed. Finally, we investigate the
      role of Doppler measurements in identifying growth-restricted babies.

PMID- 23550851
TI  - The cause and consequence of domestic violence on pregnant women in India.
AB  - The objective of this study is to evaluate and elucidate the impact of domestic
      violence on the health and pregnancy outcomes of women. Data were extracted from
      literature through the MEDLINE database for years 2000-2011. Domestic violence
      occurs in every society, irrespective of class, creed, religion and country.
      Women attending antenatal clinics in Delhi reported experience of 26.9% physical,
      29% mental and 6.2% sexual abuse, irrespective of their age. The spouse was the
      perpetrator of abuse in 47% cases and his family members were responsible for
      31%. Pregnant women were hit by their husbands on the back and abdomen, sometimes
      repeatedly, besides psychological abuse. Incidence of domestic violence was more
      when the male spouse was less educated or in the habit of consuming alcohol,
      opium or tobacco. Illiteracy, poverty, family status and uncaring attitude of
      community about spousal violence were the causes of domestic violence. Women
      having experience of violence were less likely to receive antenatal care or home
      visits by health workers and had a risk of perinatal and neonatal mortality of
      2.59 and 2.37 times higher, respectively, than women having no violence during
      pregnancy. The survey indicated that 4.5% of abused women required
      hospitalisation and 3.8% needed medical care. Women's education, economic
      autonomy and empowerment may reduce the incidence of domestic violence among
      Indian women.

PMID- 23550850
TI  - Placental mesenchymal dysplasia: a rare clinicopathologic entity confused with
      molar pregnancy.
AB  - Placental mesenchymal dysplasia (PMD) is a rare placental abnormality
      characterised by placentomegaly and grape-like vesicles resembling partial mole
      by ultrasonography, but in contrast to partial mole can co-exist with a viable
      fetus. Although the karyotype is normal, the fetus is at increased risk for
      intrauterine growth restriction, intrauterine fetal demise or perinatal death and
      Beckwith-Wiedemann syndrome. Prenatal diagnosis is difficult and the final
      diagnosis is usually achieved by postpartum histological examination of the
      placenta. We present two recent cases of placental mesenchymal dysplasia with
      poor obstetric outcome. One fetus presented with reduced growth parameters, while
      the other fetus showed hepatosplenomegaly and early hydropic changes that appear
      to be associated with Beckwith-Wiedemann syndrome. In this report, the clinico
      pathological features of two cases of PMD are discussed and the differentiation
      from a partial mole is highlighted. This study also supports the utility of
      cytogenetic ploidy analysis and p57KIP2 protein staining in the evaluation of
      pregnancies with PMD.

PMID- 23550852
TI  - Delivering health information to pregnant women in the UK.
AB  - Over the past decade, there has been a move by British governments of different
      political persuasions to push for a patient-led National Health Service (NHS).
      One of the areas of most visible change is in maternity care. Around 60% of the
      UK population use the internet every day. Our changing demography presents
      significant pressure on resources. Our antenatal clientele range from the middle
      aged professional to the non-English speaking immigrant. Meeting their varying
      information needs is both challenging and expensive. In the current economic
      climate, where efficiency saving is required across the NHS, expenditure on
      health information delivery systems is likely to be threatened by 'more acute'
      demands. We need to assess the suitability of our services and provide best value
      for money. This paper examines the information delivery systems currently
      available. We also studied their uptake and influence on our local setting as
      well as their unique challenges.

PMID- 23550853
TI  - Stereological and histopathological evaluation of ovary and uterine horns of
      female rats prenatally exposed to diclofenac sodium.
AB  - In this study, we investigated the morphometric and histological alterations of
      the ovary and uterine horns in 4-week-old rats that were prenatally exposed to
      diclofenac sodium (DS). For this purpose, pregnant rats were divided into two
      groups: the control and drug-treated groups. Beginning from the 5th day after
      mating through the 15th day of pregnancy, DS (1 mg/kg daily) was
      intraperitoneally injected in the treated group. No injection was given to the
      rats in the control group. After spontaneous delivery, male offspring were
      obtained. At the end of the 4th week, ovary and uterine horn samples were
      removed. Following dissection and routine histological preparation,
      histopathological and stereological investigations were carried out. Our results
      indicate that DS application leads to a decrease in the mean volume fraction of
      the uterine horn. Moreover, there was an increased volume fraction in some
      structures of the ovary; like the cortex, medulla and zona granulosa. There was
      no difference found between the two groups in terms of the mean volume of the
      antrum and the Graafian follicle fraction. Finally, in light of our findings, we
      may suggest that DS may lead to adverse effects in rats that are prenatally
      subjected to this drug.

PMID- 23550855
TI  - Can quadruple test parameters predict SGA infants?
AB  - The aim of this study was to investigate the role of quadruple test parameters in
      predicting the risk of delivering a small for gestational age (SGA) infant. The
      quadruple test results of patients performed at 16-18 weeks of pregnancy were
      searched retrospectively. Alpha-fetoprotein (AFP) levels higher than 2 MoM were
      associated with a risk of delivering an SGA infant (p = 0.025), sensitivity 8%,
      specificity 98%, positive predictive value 25%, negative predictive value 91%.
      Other quadruple test parameters were not related to delivery of an SGA infant.
      The introduction of AFP as a screening test for the detection of SGA infants does
      not seem feasible, but we suggest clinicians take it into account when
      counselling the patients about the results of Down syndrome screening tests.

PMID- 23550854
TI  - Circulating pro- and anticoagulant levels in normal and complicated primigravid
      pregnancies and their relationship to placental pathology.
AB  - We aimed to compare the changes in factor VIII:C, antithrombin, protein C,
      protein S and fibrinogen in a cohort of low-risk primigravida who developed
      maternal or fetal complications to those who had uncomplicated pregnancies and to
      correlate these findings with placental pathology. This is a case-control study
      of 170 cases and 122 controls selected from a prospective cohort of 1,011 low
      risk primigravida. Significantly elevated levels of factor VIII:C and
      significantly decreased levels of antithrombin were seen in women who developed
      pre-eclampsia (p <0.001), placental infarction (p < 0.001) or had infants with a
      birth weight < 3rd centile (p < 0.001). Placental villous dysmaturity was
      significantly associated with raised factor VIII:C (p < 0.001). Women who
      developed pre-eclampsia showed elevated fibrinogen at 14 weeks (p = 0.03).
      Significantly higher than normal pregnancy levels of factor VIII:C, in tandem
      with significantly lower antithrombin levels associated with certain adverse
      pregnancy outcomes, may be related to underlying placental insufficiency. This is
      supported by associated placental findings.

PMID- 23550856
TI  - Intravaginal isosorbide dinitrate or misoprostol for cervical ripening prior to
      induction of labour: a randomised controlled trial.
AB  - In this randomised double-blind controlled trial, 130 healthy pregnant women with
      term pregnancy who scheduled for labour induction with Bishop's score < 5, were
      recruited. They were assigned randomly to vaginal administration of isosorbide
      dinitrate (ISDN) (40 mg) or misoprostol (25 MUg), which were repeated after 4 h
      as needed. The efficacies of medications were evaluated by predetermined primary
      and secondary outcome variables for cervical ripening and induction of labour and
      delivery. There was no significant difference in Bishop's score 8 h after drug
      administration between the ISDN and misoprostol groups. However, in the ISDN
      group, labour induction was needed more frequently and the time from start of
      medication to the beginning of active phase of labour was significantly longer.

PMID- 23550857
TI  - A randomised controlled trial of sublingual misoprostol and intramuscular
      oxytocin for prevention of postpartum haemorrhage.
AB  - This study aims to evaluate the efficacy and side-effects of 200 MUg sublingual
      misoprostol vs 5 IU i.m. oxytocin, administered immediately following cord
      clamping in normal non-augmented vaginal delivery, in prevention of postpartum
      haemorrhage (PPH). A total of 104 women were randomised into three groups:
      misoprostol group (28 patients); oxytocin group (37 patients) and control group
      (39 patients). Misoprostol and oxytocin significantly minimised the blood loss
      during the third stage of labour and reduced the need for additional treatments
      for PPH as compared with the control group. Oxytocin was more effective than
      misoprostol in minimising blood loss and the need for additional uterotonic
      treatments. However, a significant decrease in systolic and diastolic blood
      pressure, associated with tachycardia was observed in the oxytocin group. In
      conclusion, sublingual misoprostol appears to be less effective than i.m.
      oxytocin in the prevention of PPH; however, it has the potential advantages of
      being easily used, cost-effective and stable at room temperature. Therefore,
      sublingual misoprostol is still a feasible drug for routine management of third
      stage, especially in areas with limited medical facilities.

PMID- 23550858
TI  - Is there a nuchal translucency threshold above which biochemistry is unnecessary
      for 1st trimester screening in the Chinese population?

PMID- 23550859
TI  - Is heavy menstrual bleeding investigated and managed appropriately?
AB  - Heavy menstrual bleeding (HMB) accounts for approximately 20% of gynaecology
      referrals. The National Institute of Clinical Excellence (NICE) recommendations
      provide the framework for evidence-based management of HMB. Despite this,
      previous studies have highlighted significant variation in the investigation and
      management of HMB. This was an observational study of clinical practice performed
      by retrospective case note reviews of 43 women referred to the Royal Bolton NHS
      Foundation Trust with HMB between May and June 2011. The care that these women
      received was evaluated and compared with that currently recommended by clinical
      guidelines. The investigation and management of HMB in both primary and secondary
      care was variable, often failing to meet standards recommended by NICE. Greater
      awareness of NICE guidance may result in improved care. Educational sessions and
      information provision targeted at healthcare professionals who manage women with
      HMB, may be beneficial.

PMID- 23550860
TI  - The relationship between serum prolactin concentration and pregnancy outcome in
      women with unexplained recurrent miscarriage.
AB  - The role of prolactin in early pregnancy is controversial. The aim of this study
      was to evaluate the relationship between serum prolactin concentration and the
      risk of miscarriage in women with unexplained recurrent miscarriage (RM). A
      series of 174 women with unexplained RM, who had serum prolactin concentrations
      measured from January 2000 to September 2009 at the Recurrent Miscarriage Clinic
      in Royal Hallamshire Hospital in Sheffield, were included in this study. Among
      the 174 patients with unexplained RM, 40 patients did not conceive during the
      study period, 9 were lost to follow-up and 125 patients conceived again. Patients
      who did not conceive were significantly older than those who conceived (p < 0.05,
      OR: 1.08, 95% CI: 1.03-1.13). Among those who conceived again, the pregnancy
      outcome data were available for analysis in 109 patients. Those who miscarried
      were older (p < 0.05, OR: 1.1, 95% CI: 1.01-1.22) and had significantly lower
      serum prolactin concentrations (p < 0.05, adjusted OR: 0.99, 95% CI: 0.97-0.99)
      after adjustment has been made for age, than those who had a live birth. Lower
      basal serum prolactin concentrations were associated with an increased risk of
      miscarriage in a subsequent pregnancy in women with unexplained RM.

PMID- 23550861
TI  - Efficacy of omega-3 in the treatment of polycystic ovary syndrome.
AB  - The purpose of this study was to evaluate the efficacy and safety of omega-3 in
      the treatment of polycystic ovary syndrome and to compare the clinical, hormonal,
      TNF-alpha and resistin levels in the patients treated with omega-3. A total of 45
      non-obese PCOS women were studied. Women were treated with daily oral 1,500 mg of
      omega-3 for 6 months. Body mass index (BMI), hirsutism score, fasting glucose and
      insulin levels were noted for each case. Hirsutism was assessed at 6-month
      intervals using the Ferriman-Gallwey (F-G) scoring system. Hormonal, TNF-alpha
      and resistin levels at 6 months of therapy were compared with baseline values.
      BMI, F-G scoring, insulin and HOMA levels decreased significantly during
      treatment, but glucose levels did not change. In the hormonal profile, serum LH
      and testosterone levels decreased and sex hormone-binding globulin levels
      increased significantly after the 6 months of therapy. On the other hand, TNF
      alpha levels showed a significant increase, whereas resistin levels showed no
      change. Omega-3 may be also effective in improving hirsutism and insulin
      resistance in patients with PCOS.

PMID- 23550862
TI  - Adult recall of childhood female genital cutting and perceptions of its effects:
      a pilot study for service improvement and research feasibility.
AB  - This study aimed to gather information from service users of an African Women's
      Clinic for the purposes of planning service improvement and estimating research
      feasibility. The report is based on 17 interviews with Somali speaking women who
      had experienced female genital cutting in childhood. With language barriers
      removed, a high percentage of clinic attendees responded positively to the
      invitation to participate in research. They willingly discussed their experiences
      of FGM and expressed their negative viewpoints about the practice of FGM,
      suggesting that psychosocial and psychosexual research may be feasibly carried
      out in specialist contexts. The results also point to the need for psychological
      and educational input for service improvement.

PMID- 23550863
TI  - Does an enhanced recovery integrated care pathway (ICP) encourage adherence to
      prescribing guidelines, accelerate postoperative recovery and reduce the length
      of stay for gynaecological oncology patients?
AB  - A new integrated care pathway (ICP) proforma for gynaecological oncology patients
      was developed and introduced in early 2010. The ICP is a goal-defined and time
      specified documentation by gynaecological oncology doctors and nurses, guided by
      certain parameters to be achieved in pre and postoperative days. All patients
      were admitted to the same unit and underwent a major abdominal/pelvic procedure
      for confirmed or suspected gynaecological malignancy, including hysterectomy and
      oophorectomy. The control group included 58 randomly selected patients from May
      2008 to March 2009 and the intervention group comprised 52 patients, after the
      introduction of the ICP. The effectiveness was assessed with a variety of
      measurements: the duration of intraperitoneal drains, urethral catheters and
      intravenous fluids postoperatively; time taken for the patient to eat and drink;
      time taken to mobilisation; and the total length of stay in hospital. We also
      assessed whether the implementation of the care pathway was associated with an
      increase in adherence to prescribing guidelines for thromboprophylaxis and
      postoperative antibiotics and sodium docusate. The new ICP encouraged clearer
      documentation and regular review of fluids, drains and catheters. There was a
      modest reduction in the length of stay and an increase in prescribed
      thromboprophylaxis and sodium docusate ( Cheung et al. 2011 ).

PMID- 23550864
TI  - A review of molar pregnancy at the university hospital of the West Indies over a
      16-year period.
AB  - There is a wide variation in reported incidence, risk factors and presentation of
      molar pregnancy. This necessitates population-based studies to determine these
      parameters at the University Hospital of the West Indies, which is a referral
      centre for these conditions. The incidence of molar pregnancy at the University
      Hospital of the West Indies was found to be 2.81 per 1,000, which fell in the
      range of worldwide values. Partial moles made up 61.1% and complete moles 31.0%.
      The mean age of the patients was 28.49 years old with 85% of patients aged
      between 20 and 40 years old. The median gestational age by dates was 12 weeks and
      vaginal bleeding was the most common presenting symptom (77%). A significant
      number of cases (52.2%) of molar pregnancy were diagnosed by routine
      histopathology for failed pregnancy and not by pre-evacuation ultrasound. The
      practice of routine assessment of tissue from failed pregnancy should therefore
      be encouraged in our population.

PMID- 23550865
TI  - Platelet volume as a parameter for platelet activation in patients with
      endometrial cancer.
AB  - The objective of this study was to use mean platelet volume (MPV) as a measure of
      platelet activation in patients with endometrial adenocarcinoma and healthy
      controls. There was a total of 310 patients with endometrial adenocarcinoma
      retrospectively evaluated and 250 healthy controls. Preoperative haemoglobin,
      platelet counts and mean platelet volume were evaluated and statistical tests
      were conducted to determine the differences among early and advanced disease
      groups and controls. Median haemoglobin (13.0 vs 13.3 g/dl) and platelet count
      (282,000 vs 280,000/MUl) values were similar in patients with endometrial
      adenocarcinoma and healthy controls (p > 0.05). Subjects with endometrial cancer
      exhibited slightly higher MPV than the control group (8.4 fl vs 8.2 fl) (p =
      0.048). In patients with advanced-stage endometrial cancer, haemoglobin was
      significantly lower (p < 0.05) and MPV was significantly higher (p < 0.05) than
      in either patients with early-stage endometrial cancer or the control group. It
      was concluded that MPV was found to be a marker for predicting advanced-stage
      endometrial cancers.

PMID- 23550866
TI  - Delays in presentation and management of ovarian cancer in Lagos, Nigeria.
AB  - This study highlights the extent of delays in the presentation and management of
      ovarian cancer at the Lagos State University Teaching Hospital. A total of 37
      histologically confirmed epithelial ovarian cancer cases managed from January
      2004 to December 2008 were analysed. The time interval between onset of symptoms
      and seeking healthcare, was 36.1 +/- 40.8 weeks; between seeking healthcare and
      referral to tertiary hospital, was 22.7 +/- 30.4 weeks; and the overall time
      interval from onset of symptoms to presentation for definitive care, was 52.0 +/-
      51.8 weeks. Private hospitals (35.1%) and herbal homes (21.6%) were the commonest
      facilities first visited. A total of 32 (86.5%) of the patients presented in
      stages III and IV. The overall compliance rate for recommended chemotherapy was
      11.1%. Ovarian cancer in Lagos, Nigeria is characterised by patient-related
      delays in presentation, provider-related delays in referrals and poor compliance
      with recommended chemotherapy.

PMID- 23550867
TI  - Chiari network in pregnancy.

PMID- 23550868
TI  - Prenatal diagnosis of Pfeiffer syndrome prior to 20 weeks' gestation.

PMID- 23550869
TI  - Revisiting lactic acidosis in an HIV-1 infected pregnant woman on antiretroviral
      therapy.

PMID- 23550870
TI  - Twin pregnancy with a complete hydatidiform mole and co-existent healthy fetus:
      unusual case of complete resorption of molar pregnancy.

PMID- 23550871
TI  - Spontaneous arrest of flow in a TRAP sequence.

PMID- 23550872
TI  - The difficult PPH: experience of combined use of B-Lynch brace suture and
      intrauterine Bakri balloon in York hospital, UK.

PMID- 23550873
TI  - Anomalous ovarian morphology in a patient with craniofrontonasal syndrome.

PMID- 23550874
TI  - Mullerian anomaly with ovary at deep inguinal ring: a rare case finding.

PMID- 23550875
TI  - Isolated fallopian tube torsion: a rare variant of a common entity with
      successful laparoscopic detorsion.

PMID- 23550876
TI  - Lichen sclerosus occurring on vaginal mucosa secondary to uterine prolapse.

PMID- 23550877
TI  - Simple vulval trichilemmal cyst.

PMID- 23550878
TI  - Cervical schistosomiasis: an increasing presentation in the developed world.

PMID- 23550879
TI  - Spontaneous uterine perforation due to pyometra.

PMID- 23550880
TI  - Serous papillary cystadenocarcinoma in supernumerary ovary.

PMID- 23550881
TI  - Aggressive angiomyxoma of the vulva.

PMID- 23550883
TI  - Micro-scale determinants of bacterial diversity in soil.
AB  - Soil habitats contain vast numbers of microorganisms and harbor a large portion
      of the planet's biological diversity. Although high-throughput sequencing
      technologies continue to advance our appreciation of this remarkable phylogenetic
      and functional diversity, we still have only a rudimentary understanding of the
      forces that allow diverse microbial populations to coexist in soils. This
      conspicuous knowledge gap may be partially due the human perspective from which
      we tend to examine soilborne microorganisms. This review focusses on the highly
      heterogeneous soil matrix from the vantage point of individual bacteria. Methods
      describing micro-scale soil habitats and their inhabitants based on sieving,
      dissecting, and visualizing individual soil aggregates are discussed, as are
      microcosm-based experiments allowing the manipulation of key soil parameters. We
      identify how the spatial heterogeneity of soil could influence a number of
      ecological interactions promoting the evolution and maintenance of bacterial
      diversity. 

PMID- 23550885
TI  - Validity and reliability of the Spineangel lumbo-pelvic postural monitor.
AB  - OBJECTIVE: to determine the reliability and the concurrent validity of the
      Spineangel lumbo-pelvic postural monitoring device. METHODS: the dynamic lumbo
      pelvic posture of 25 participants was simultaneously monitored by the Spineangel
      and Fastrak devices. Participants performed six different functional tasks in
      random order. Within-task, within-session and between-day intraclass correlation
      coefficients (ICC(3,1), ICC(3,5), ICC(2,5), respectively) reliability were
      calculated for Spineangel measurements. Concurrent validity of the Spineangel was
      assessed by means of a Bland and Altman plot and by means of Pearson's
      correlation coefficient and paired t-test. RESULTS: within-task, within-session
      and between-day ICC for the Spineangel were found to be excellent (>0.93). The
      Spineangel and Fastrak pelvic measurements were found to have a good correlation
      (R = 0.77). CONCLUSION: the Spineangel is a reliable and valid device for
      monitoring general lumbo-pelvic movements when clipped on the belt or waistband
      of workers' clothing during various occupational activities. PRACTITIONER
      SUMMARY: The Spineangel can be used for assessing lumbo-pelvic posture during
      work or daily-life activities. This device was found to provide reliable and
      valid measurements for lumbo-pelvic movements. Further research is required to
      determine whether the use of this device is clinically relevant for patients
      presenting with low back pain.

PMID- 23550884
TI  - Financial errors in dementia: testing a neuroeconomic conceptual framework.
AB  - Financial errors by patients with dementia can have devastating personal and
      family consequences. We developed and evaluated a neuroeconomic conceptual
      framework for understanding financial errors across different dementia syndromes,
      using a systematic, retrospective, blinded chart review of demographically
      balanced cohorts of patients with Alzheimer's disease (AD, n=100) and behavioral
      variant frontotemporal dementia (bvFTD, n=50). Reviewers recorded specific
      reports of financial errors according to a conceptual framework identifying
      patient cognitive and affective characteristics, and contextual influences,
      conferring susceptibility to each error. Specific financial errors were reported
      for 49% of AD and 70% of bvFTD patients (p = 0.012). AD patients were more likely
      than bvFTD patients to make amnestic errors (p < 0.001), while bvFTD patients
      were more likely to spend excessively (p = 0.004) and to exhibit other behaviors
      consistent with diminished sensitivity to losses and other negative outcomes (p <
      0.001). Exploratory factor analysis identified a social/affective vulnerability
      factor associated with errors in bvFTD, and a cognitive vulnerability factor
      associated with errors in AD. Our findings highlight the frequency and functional
      importance of financial errors as symptoms of AD and bvFTD. A conceptual model
      derived from neuroeconomic literature identifies factors that influence
      vulnerability to different types of financial error in different dementia
      syndromes, with implications for early diagnosis and subsequent risk prevention. 

PMID- 23550886
TI  - Metabolic perturbation of an essential pathway: evaluation of a glycine precursor
      of coenzyme A.
AB  - Pantetheine and its corresponding disulfide pantethine play a key role in
      metabolism as building blocks of coenzyme A (CoA), an essential cofactor utilized
      in ~4% of primary metabolism and central to fatty acid, polyketide, and
      nonribosomal peptide synthases. Using a combination of recombinant engineering
      and chemical synthesis, we show that the disulfide of N-pantoylglycyl-2
      aminoethanethiol (GlyPan), with one fewer carbon than pantetheine, can rescue a
      mutant E. coli strain MG1655DeltapanC lacking a functional pantothenate
      synthetase. Using mass spectrometry, we show that the GlyPan variant is accepted
      by the downstream CoA biosynthetic machinery, ultimately being incorporated into
      essential acyl carrier proteins. These findings point to further flexibility in
      CoA-dependent pathways and offer the opportunity to incorporate orthogonal
      analogues.

PMID- 23550887
TI  - Evaluation of postmortem bacterial migration using culturing and real-time
      quantitative PCR.
AB  - Postmortem bacteriology can be a valuable tool for evaluating deaths due to
      bacterial infection or for researching the involvement of bacteria in various
      diseases. In this study, time-dependent postmortem bacterial migration into
      liver, mesenteric lymph node, pericardial fluid, portal, and peripheral vein was
      analyzed in 33 autopsy cases by bacterial culturing and real-time quantitative
      polymerase chain reaction (RT-qPCR). None suffered or died from bacterial
      infection. According to culturing, pericardial fluid and liver were the most
      sterile samples up to 5 days postmortem. In these samples, multigrowth and
      staphylococci were not or rarely detected. RT-qPCR was more sensitive and showed
      higher bacterial positivity in all samples. Relative amounts of intestinal
      bacterial DNA (bifidobacteria, bacteroides, enterobacter, clostridia) increased
      with time. Sterility of blood samples was low during the studied time periods (1
      7 days). The best postmortem microbiological sampling sites were pericardial
      fluid and liver up to 5 days after death.

PMID- 23550888
TI  - The K+/H+ antiporter LeNHX2 increases salt tolerance by improving K+ homeostasis
      in transgenic tomato.
AB  - The endosomal LeNHX2 ion transporter exchanges H(+) with K(+) and, to lesser
      extent, Na(+) . Here, we investigated the response to NaCl supply and K(+)
      deprivation in transgenic tomato (Solanum lycopersicum L.) overexpressing LeNHX2
      and show that transformed tomato plants grew better in saline conditions than
      untransformed controls, whereas in the absence of K(+) the opposite was found.
      Analysis of mineral composition showed a higher K(+) content in roots, shoots and
      xylem sap of transgenic plants and no differences in Na(+) content between
      transgenic and untransformed plants grown either in the presence or the absence
      of 120 mm NaCl. Transgenic plants showed higher Na(+)/H(+) and, above all,
      K(+)/H(+) transport activity in root intracellular membrane vesicles. Under K(+)
      limiting conditions, transgenic plants enhanced root expression of the high
      affinity K(+) uptake system HAK5 compared to untransformed controls. Furthermore,
      tomato overexpressing LeNHX2 showed twofold higher K(+) depletion rates and half
      cytosolic K(+) activity than untransformed controls. Under NaCl stress,
      transgenic plants showed higher uptake velocity for K(+) and lower cytosolic K(+)
      activity than untransformed plants. These results indicate the fundamental role
      of K(+) homeostasis in the better performance of LeNHX2 overexpressing tomato
      under NaCl stress.

PMID- 23550889
TI  - A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in
      patients from a consanguineous Tunisian family.
AB  - Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically
      heterogeneous group of hereditary neuropathies characterized by progressive
      muscular and sensory loss in the distal extremities with chronic distal weakness,
      deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal
      recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for
      which nine mutations are described to date. In this study, we describe three
      patients from a consanguineous Tunisian family, presenting with severe, early
      onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by
      mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we
      report the identification of a novel homozygous frameshift mutation in FGD4:
      c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified
      in FGD4 in Tunisian patients affected with CMT. It further confirms the important
      clinical heterogeneity observed in patients with mutations in FGD4 and the lack
      of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should
      be screened in other early-onset CMT subtypes, regardless of the severity of the
      phenotype, and particularly in patients of consanguineous descent. In Tunisians,
      as in other populations with high consanguinity rates, screening of genes
      responsible for rare autosomal recessive CMT subtypes should be prioritized. 

PMID- 23550890
TI  - Characterization of residual medium peptides from Yersinia pestis cultures.
AB  - Here we demonstrate that when Yersinia pesitis is grown in laboratory media,
      peptides from the medium remain associated with cellular biomass even after
      washing and inactivation of the bacteria by different methods. These peptides are
      characteristic of the type of growth medium and of the manufacturer of the
      medium, reflecting the specific composition of the medium. We analyzed biomass
      associated peptides from cultures of two attenuated strains of Yersinia pestis
      [KIM D27 (pgm-) and KIM D1 (lcr-)] grown in several formulations of 4 different
      media (tryptic soy broth (TSB), brain-heart infusion (BHI), Luria-Bertani broth
      (LB), and glucose (G) medium) made from components purchased from different
      suppliers. Despite the range of growth medium sources and the associated
      manufacturing processes used in their production, a high degree of peptide
      similarity was observed for a given medium recipe; however, notable differences
      in the termination points of select peptides were observed in media formulated
      using products from some suppliers, presumably reflecting the process by which a
      manufacturer performed protein hydrolysis for use in culture media. These results
      may help explain the presence of peptides not explicitly associated with target
      organisms during proteomic analysis of microbes and other biological systems that
      require culturing. While the primary aim of this work is to outline the range and
      type of medium peptides associated with Yersinia pestis biomass and improve the
      quality of proteomic measurements, these peptides may also represent a
      potentially useful forensic signature that could provide information about
      microbial culturing conditions.

PMID- 23550891
TI  - Immune system alterations in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a disease of which the underlying cause and
      pathogenesis are unknown. Cumulatative data clearly indicates an active
      participation by the immune system in the disease. An increasingly recognized
      theory suggests a non-cell autonomous mechanism, meaning that multiple cells
      working together are necessary for the pathogenesis of the disease. Observed
      immune system alterations could indicate an active participation in this
      mechanism. Damaged motor neurons are able to activate microglia, astrocytes and
      the complement system, which further can influence each other and contribute to
      neurodegeneration. Infiltrating peripheral immune cells appears to correlate with
      disease progression, but their significance and composition is unclear. The
      deleterious effects of this collaborating system of cells appear to outweigh the
      protective aspects, and revealing this interplay might give more insight into the
      disease. Markers from the classical complement pathway are elevated where its
      initiator C1q appears to derive primarily from motor neurons. Activated microglia
      and astrocytes are found in close proximity to dying motor neurons. Their
      activation status and proliferation seemingly increases with disease progression.
      Infiltrating monocytes, macrophages and T cells are associated with these areas,
      although with mixed reports regarding T cell composition. This literature review
      will provide evidence supporting the immune system as an important part of ALS
      disease mechanism and present a hypothesis to direct the way for further studies.

PMID- 23550892
TI  - Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2
      and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and
      hypertension among Japanese alcoholic men.
AB  - BACKGROUND: The presence of the less-active form of alcohol dehydrogenase-1B
      encoded by ADH1B*1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase-2
      (ALDH2) encoded by ALDH2*1/*1 (vs. *2 allele) increases the risk of alcoholism in
      East Asians. METHODS: The subjects in this cross-sectional survey were 1,902
      Japanese alcoholic men (>=40 years) who underwent ADH1B/ALDH2 genotyping.
      RESULTS: Age-adjusted daily alcohol consumption did not differ according to the
      ADH1B/ALDH2 genotypes. The age-adjusted odds ratios (AORs; 95% confidence
      interval) for liver cirrhosis (LC; n = 359, 1.58 [1.19 to 2.09]), chronic
      calcific pancreatitis (CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus
      (DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B*2 allele carriers
      than in the ADH1B*1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68
      [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension (HT; n = 495, 1.52
      [1.11 to 2.07]) were higher in the ALDH2*1/*1 carriers than in the ALDH2*1/*2
      carriers. The ADH1B*2-associated AOR for LC was 2.08 (1.46 to 2.94) among those
      aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over,
      and the interaction between ADH1B genotype and age on the LC risk was significant
      (p = 0.009). When the group with non-LC and no/mild fibrosis was used as
      controls, the ADH1B*2-associated AORs increased according to the severity of
      their liver disease: 1.67 (1.32 to 2.11) for the group with non-LC and serum type
      IV collagen values >=200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child-Pugh
      class A LC, and 3.17 (1.98 to 5.07) for the group with Child-Pugh class B/C LC.
      Anti-hepatitis C virus (HCV) antibody was positive in 103 patients, and the
      groups with a high anti-HCV antibody titer and either the ADH1B*2/*2 genotype or
      the ALDH2*1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The
      population attributable fraction (PAF) due to the ADH1B*2 allele was 29% for LC,
      47% for CP, and 27% for DM, and the PAF due to the ALDH2*1/*1 genotype was 26%
      for LC, 34% for DM, and 30% for HT. CONCLUSIONS: The ADH1B*2 allele increased the
      AORs for LC, CP, and DM of the alcoholics, and the ALDH2*1/*1 genotype increased
      their AORs for LC, DM, and HT. HCV infection and genetic susceptibility had a
      synergistic effect on the AOR for LC.

PMID- 23550893
TI  - Gingival crevicular fluid levels of interferon-gamma, but not interleukin-4 or 
      33 or thymic stromal lymphopoietin, are increased in inflamed sites in patients
      with periodontal disease.
AB  - OBJECTIVE: To investigate the hypothesis that levels of interferon (IFN)-gamma
      and interleukin (IL)-4, as well as the newer cytokines IL-33 and thymic stromal
      lymphopoietin (TSLP), in gingival crevicular fluid (GCF) samples differ from
      sites of patients at various clinical stages of periodontal disease and controls.
      BACKGROUND: Periodontal diseases result from the complex interplay between
      pathogenic bacteria and the host's immune responses. Several inflammatory
      mediators, such as IFN-gamma and IL-4, have been detected in GCF samples in
      patients with periodontitis, but the results are mostly contradicting due to the
      lack of uniformity and collection of sites and methods of analysis. MATERIAL AND
      METHODS: GCF samples were collected from sites with different clinical
      characteristics (healthy, gingivitis and periodontitis sites) from periodontally
      healthy ( n = 14), plaque-induced gingivitis (n = 17) and chronic periodontitis
      (n = 11) subjects. The GCF samples were analyzed for the frequency of detection
      and levels of IFN-gamma, IL-4, IL-33 and TSLP using a multiplex bead immunoassay.
      RESULTS: Inflamed sites in both patients with plaque-induced gingivitis and
      chronic periodontitis showed statistically significantly higher volume of GCF
      compared to non-inflamed sites in all patients. IFN-gamma could be detected in
      about 50-70% of the samples analyzed and at significantly higher levels in sites
      with periodontitis compared to healthy sites in patients with chronic
      periodontitis (p = 0.035). We also show a statistically significant decrease of
      IFN-? in healthy sites of patients with chronic periodontitis as compared to
      gingivitis sites in patients with plaque-induced gingivitis (p = 0.047). Only
      some of the GCF samples showed detectable levels for IL-4 and TSLP, while IL-33
      was below the detection level in all samples collected. CONCLUSIONS: These
      results suggest that IFN-gamma levels in GCF depend on the clinical stage of the
      site and not on the disease stage of the patient, but need to be expanded to a
      greater number of subjects and additional analysis of corresponding gingival
      tissue biopsies for cytokine gene expression.

PMID- 23550894
TI  - Longitudinal changes in high-density lipoprotein cholesterol and cardiovascular
      events in older adults.
AB  - OBJECTIVE: While low high-density lipoprotein cholesterol (HDL-C) is associated
      with increased risk of cardiovascular (CV) events, there are limited data
      evaluating the association of longitudinal change in HDL-C with CV event risk in
      older populations. The aim of this study was to examine the association between
      within-subject changes in HDL-C levels and CV events in an older population.
      DESIGN: Observational cohort study. PATIENTS: 1293 men and 1422 women age >=50
      years, with >=2 consecutive HDL measurements, and no prior CVD as part of
      Framingham Offspring Study. MEASUREMENTS: A clinical CV event was defined as the
      first occurrence of any of the following: coronary heart disease (coronary death,
      myocardial infarction, coronary insufficiency and angina), cerebrovascular event,
      peripheral artery disease or heart failure. RESULTS: Median total follow-up time
      across subjects was 9.6 years. Change in HDL-C was evaluated as between-exam
      (approximately 3.5 years) percentage change in HDL-C, categorized as >=10%
      decrease, <10% change (stable) and >=10% increase. Crude and adjusted sex
      specific Cox hazards regression models with change in HDL-C as a time-dependent
      covariate quantified the association with CV events. Mean baseline age of the
      analysis sample was 53 years. There were 233 and 111 CV events among men and
      women, respectively. Change in HDL-C was not significantly associated with CVD
      incidence in men or women, without or with adjustment for confounders including
      baseline HDL-C or use of relevant medications. CONCLUSION: In conclusion,
      relatively short-term (3.5 years) changes in HDL-C levels do not affect CV events
      in men and women.

PMID- 23550895
TI  - Social provision and loneliness among older people suffering from chronic
      physical illness. A mixed-methods approach.
AB  - AIMS: To describe and compare the perceived social provision for a group
      reporting never feeling lonely with that of a group reporting feeling lonely and
      to explore the meaning of loneliness. SUBJECTS: Participants (N = 101) were
      recruited from geriatric wards. Inclusion criteria were as follows: aged 65 years
      or more, the absence of dementia, one or more chronic physical disorders and
      plans to be discharged from the hospital to their home. The mean age was 81.3
      years (range: 65-96 years), 68% were women, and 66% lived alone. MEASURES:
      Assessments of social provisions and loneliness were collected by a subjective
      report using the Social Provision Scale (SPS), and the Montgomery-Aasberg
      Depression Rating Scale (MADRS) was used to assess depression. The participants
      were also asked whether they felt lonely and were then asked to describe the
      meaning of loneliness if they had indicated feeling lonely. Narratives were then
      condensed by the participants into short sentences. RESULTS: Seventy-five per
      cent of the participants reported feeling lonely, of these 54% were living alone,
      and 18% identified with depression. Three subscales of SPS scores were
      significantly lower in the lonely group: attachment (p < 0.001), a sense of
      reliable alliance (p = 0.001) and the obtaining of guidance (p = 0.01). The
      overall view of the experience of loneliness was dominated by emptiness and
      negative emotions. The following themes were identified: Emotions were dominated
      by sadness, anxiety and restlessness, anger and guilt. Relationships were
      dominated by being left alone, being confined and feeling useless. Existential
      dimensions were characterised by emptiness, endless boredom, isolation and the
      potential for change. CONCLUSION: The study shows that loneliness is prevalent
      among older people suffering from chronic physical illness and confirms the
      complexity of the concept. A mixed-methods design contributed to nuanced and
      detailed information about the meaning of loneliness.

PMID- 23550896
TI  - Evidence for outcomes of motivational rehabilitation interventions for children
      and adolescents with cerebral palsy: an American Academy for Cerebral Palsy and
      Developmental Medicine systematic review.
AB  - This study reviewed evidence regarding the effect of motivational rehabilitation
      interventions on outcomes in children with cerebral palsy. Six databases were
      searched for literature published up to May 2012. Included studies measured the
      purported motivating effects of motor-based rehabilitation interventions and the
      measured impact on outcomes. The American Academy for Cerebral Palsy and
      Developmental Medicine (AACPDM) systematic review methodology was used as a
      framework. Eight studies evaluated outcomes of studies using virtual reality
      interventions and one in a functional therapy context. Conflicting evidence from
      three (level II and level III) studies exists about the impact of these
      motivating interventions on motor outcomes measured in body functions. No
      statistical evidence regarding activity and participation outcomes exists. A
      single level II study found no significant difference in participants' motivation
      between motivational and conventional interventions. This review revealed a
      paucity of research on the effects of motivational interventions. Weaknesses
      include a lack of consistency in the examination of motivational interventions,
      limited use of definitions or theories to ground the concept of motivation, and
      reliance on non-validated methodological tools. This body of evidence would be
      strengthened by the use and development of robust outcome measures of motivation.

PMID- 23550897
TI  - A new method for estimating recharge to unconfined aquifers using differential
      river gauging.
AB  - In semiarid and arid environments, leakage from rivers is a major source of
      recharge to underlying unconfined aquifers. Differential river gauging is widely
      used to estimate the recharge. However, the methods commonly applied are limited
      in that the temporal resolution is event-scale or longer. In this paper, a novel
      method is presented for quantifying both the total recharge volume for an event,
      and variation in recharge rate during an event from hydrographs recorded at the
      upstream and downstream ends of a river reach. The proposed method is applied to
      river hydrographs to illustrate the method steps and investigate recharge
      processes occurring in a sub-catchment of the Murray Darling Basin (Australia).
      Interestingly, although it is the large flood events which are commonly assumed
      to be the main source of recharge to an aquifer, our analysis revealed that the
      smaller flow events were more important in providing recharge. 

PMID- 23550898
TI  - General synthetic approach to functionalized dihydrooxepines.
AB  - A three-step sequence to access functionalized 4,5-dihydrooxepines from
      cyclohexenones has been developed. This approach features a regioselective Baeyer
      Villiger oxidation and subsequent functionalization via the corresponding enol
      phosphate intermediate.

PMID- 23550899
TI  - The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy
      option.
AB  - INTRODUCTION: Mirabegron is a new once-daily, oral treatment for management of
      overactive bladder (OAB) that is approved in USA, EU and Japan. It activates
      beta3 adrenoceptor to facilitate bladder filling and reduce mean micturition
      frequency with better safety profile than current treatment of antimuscarinic
      drugs. AREAS COVERED: The following article reviews the information available
      from published randomized trials on the metabolism and pharmacokinetics
      mirabegron. The reader will gain better insight into the variability in plasma
      exposure of mirabegron due to various causes. Propensity for drug interactions
      with mirabegron is low as its clearance involves multiple metabolic and excretory
      pathways. Mirabegron is generally well tolerated, but its pharmacokinetics is
      altered by dose and gender with implications for cardiovascular toxicity. EXPERT
      OPINION: Mirabegron is a first-in-class of beta3 adrenoceptor agonists that could
      offer an alternative to antimuscarinics for OAB patients. The marketed dose of 50
      mg achieves primary efficacy endpoints but causes only modest improvement over
      placebo in terms of daily incontinence and voiding episodes. Involvement of
      saturable efflux transporters is indicated in oral bioavailability of mirabegron.
      It is well tolerated with hypertension, nasopharyngitis, urinary tract infection
      and headache being the most common side effects.

PMID- 23550900
TI  - A land use regression model for ultrafine particles in Vancouver, Canada.
AB  - Methods to characterize chronic exposure to ultrafine particles (UFP) can help to
      clarify potential health effects. Since UFP are not routinely monitored in North
      America, spatiotemporal models are one potential exposure assessment methodology.
      Portable condensation particle counters were used to measure particle number
      concentrations (PNC) to develop a land use regression (LUR) model. PNC, wind
      speed and direction were measured for sixty minutes at eighty locations during a
      two-week sampling campaign. We conducted continuous monitoring at four additional
      locations to assess temporal variation. LUR modeling utilized 135 potential
      geographic predictors including: road length, vehicle density, restaurant
      density, population density, land use and others. A novel approach incorporated
      meteorological data through wind roses as alternates to traditional circular
      buffers. The range of measured (sixty-minute median) PNC across locations varied
      seventy-fold (1500-105000 particles/cm(3), mean [SD] = 18200 [15900]
      particles/cm(3)). Correlations between PNC and concurrently measured two-week
      average NOX concentrations were 0.6-0.7. A PNC LUR model (R(2) = 0.48, leave-one
      out cross validation R(2) = 0.32) including truck route length within 50 m,
      restaurant density within 200 m, and ln-distance to the port represents the first
      UFP LUR model in North America. Models incorporating wind roses did not explain
      more variability in measured PNC.

PMID- 23550901
TI  - Establishing likelihood ratios for patterned garment comparisons from seam
      measurement data.
AB  - It is often challenging to ascribe an objective measure of confidence for
      identifications based on surveillance imagery from a crime scene. The present
      work seeks to address this deficiency in the case of garment comparison evidence
      by developing a quantitative method for establishing a conservative lower bound
      on the likelihood ratio (LR) for identifications involving patterned garments.
      The method is based on statistical analysis of pattern offset measurements taken
      from a sample of garments of the same type (manufacturer, style, and size) as the
      seized evidence. The developed analysis framework was demonstrated on different
      types of garments over a range of modeled surveillance imaging scenarios with
      variable image quality; the lower bounds on the LRs ranged from approximately 10
      1 to over 400-1. The statistical model was tested and validated through a large
      scale empirical study involving both simulated and human observer-performed
      garment comparisons.

PMID- 23550902
TI  - Developmental personality types from childhood to adolescence: associations with
      parenting and adjustment.
AB  - This study examined whether changes in children's self-reported Big Five
      dimensions are represented by (developmental) personality types, using a cohort
      sequential design with three measurement occasions across 5 years (four cohorts,
      9-12 years at T1; N = 523). Correlates of, and gender differences in, type
      membership were examined. Latent class growth modeling yielded three personality
      types: Resilients (highest initial levels on all Big Five), Overcontrollers
      (lowest Extraversion, Emotional Stability, Imagination), and Undercontrollers
      (lowest Benevolence, Conscientiousness). Gender differences in type membership
      were small. Warm parenting, but not overreactive discipline, in childhood was
      associated with type membership. The types differed in adjustment problems by the
      end of middle adolescence. Personality change more likely occurs at the level of
      dimensions within types than in type membership.

PMID- 23550903
TI  - A convenient qualitative and quantitative method to investigate RHD-RHCE hybrid
      genes.
AB  - BACKGROUND: Molecular biology techniques, such as single specific-primer
      polymerase chain reaction (PCR), denaturing-high performance liquid
      chromatography, direct sequencing, next-generation sequencing, and microarray
      platforms, contribute to the efficient genotyping of the human blood group RHD
      gene. However, some alleles remain undetermined in rare cases in DNA samples
      carrying two copies of the RHD gene, which challenge the identification of D-CE
      hybrid genes. STUDY DESIGN AND METHODS: We set up, in a single-tube format, a
      qualitative and quantitative assay based on multiplex PCR of short fluorescent
      fragments (QMPSF) to simultaneously amplify all 10 RHD exons on the one hand and
      all 10 RHCE exons on the other hand. RESULTS: The test proved to be useful to
      rapidly identify hybrid genes in hemizygous RHD samples carrying a hybrid D-CE
      gene and to resolve unknown genotypes by quantifying individual exons in compound
      heterozygous samples, but also unexpectedly helped to redefine the RHDPsi
      haplotype. While validating the test, two novel single-point variants, c.648G>C
      (p.L216F) and c.1048G>C (p.D350H), were found. CONCLUSION: For the first time, a
      QMPSF-based method is reliable to individually quantify the exons of both RH
      genes, including hybrid D-CE genes in compound heterozygous samples and may help
      to investigate samples with unknown RHD and/or RHCE status.

PMID- 23550904
TI  - Myoepithelial carcinoma of minor salivary glands.

PMID- 23550905
TI  - Photobiological safety evaluation of UV nail lamps.
AB  - We evaluated six UV nail lamps representative of major US manufacturers to
      evaluate radiant hazards as defined in ANSI/IESNA RP-27 Recommended Practice for
      Photobiological Safety. Lamps were evaluated at three positions, 1 cm above the
      inner surface approximating exposure to the hand and the 20 cm RP-27 non-general
      light source distance, oriented normal and 45 degrees  to the opening. Hazard to
      skin at intended use distance classified these devices into Risk Group 1 or 2
      (Low to Moderate) with S(lambda) weighted Actinic UV ranging 1.2-1.7 MUW cm(-2)
      and 29.8-276.25 min permissible daily exposure. At 20 cm on center and 45 degrees
      UV risk to skin and eyes were all within Exempt classification. Actinic UV
      ranged 0.001-0.078 MUW cm(-2) and unweighted near UV (320-400 nm) ranged 0.001
      0.483 mW cm(-2). Likewise the retinal photochemical blue light hazard and retinal
      thermal and cornea/lens IR were also Exempt. One device had aphakic eye hazard
      slightly rising into Risk Group 1 (Low). There were no other photobiological
      risks to normal individuals. Total exposure following programmed times and steps
      accumulate to only a small fraction of RP-27 permissible daily occupational
      exposure. These risks are further mitigated in realistic nonoccupational use
      scenarios as it is unlikely to be a daily occurrence.

PMID- 23550906
TI  - Ulipristal acetate - safety and pharmacokinetics following multiple doses of 10
      50 mg per day.
AB  - WHAT IS KNOWN AND OBJECTIVE: Ulipristal acetate (UPA) is a novel selective
      progesterone receptor modulator for benign gynaecological conditions such as
      uterine myoma. The safety and pharmacokinetics of multiple-dose UPA and its N
      mono-demethylated metabolite, PGL4002, were investigated in women. METHODS: The
      double-blind, placebo-controlled study randomized 32 healthy women of
      reproductive age to receive 10 consecutive daily doses of placebo, 10, 20 or 50
      mg UPA. Safety assessments included vital signs, physical examination, ECG,
      clinical laboratory tests and reporting of adverse events. Blood samples for
      pharmacokinetic analysis were collected on Days 1 and 10 at intervals until 168 h
      after multiple dosing. RESULTS: UPA was well tolerated at all doses. Mild or
      moderate adverse events occurred with similar frequency in UPA and placebo
      groups. UPA median tmax was 0.75 and 0.89 h, and mean plasma half-life was
      between 38 and 49 h. Cmax values (Day 1) were 42.2, 130.9 and 354.8 ng/mL for the
      UPA 10, 20 and 50 mg treatment groups, respectively. Corresponding Cmax values
      for Day 10 were 63.7, 169.8 and 454.9 ng/mL. AUCSS values on Day 10 were 216.6,
      602.8 and 1655.7 ng h/mL after 10, 20 and 50 mg UPA, respectively. For the
      principal metabolite PGL4002, tmax and plasma elimination half-life values were
      similar to those of UPA. PGL4002 AUCSS Day 10 values were 84.7, 203.6 and 452.1
      ng h/mL for 10, 20 and 50 mg groups, respectively. WHAT IS NEW AND CONCLUSION:
      Daily administration of UPA at therapeutic and supratherapeutic doses was well
      tolerated by women of reproductive age. UPA exposure increases with dose.
      Exposure to PGL4002 is approximately one-third that of UPA.

PMID- 23550907
TI  - Improvement of Karmali agar by addition of polymyxin B for the detection of
      Campylobacter jejuni and C. coli in whole-chicken carcass rinse.
AB  - The Karmali agar was modified by supplementation with a high concentration of
      polymyxin B. The goal of the study was to evaluate the effect of a high
      concentration of polymyxin B on the ability and selectivity of the modified
      Karmali agar to isolate Campylobacter jejuni and Campylobacter coli from whole
      chicken carcass rinse. A total of 80 whole chickens were rinsed with 400 mL of
      buffer peptone water. The rinsed samples were incubated with 2* blood-free
      modified Bolton enrichment broth for 48 h, and then streaked onto unmodified
      Karmali agar and modified Karmali agar supplemented with 100000 IU/L polymixin B
      (P-Karmali agar). The suspected colonies were finally confirmed by colony PCR.
      The P-Karmali agar exhibited a significantly better (P < 0.05) isolation rate
      than the unmodified Karmali agar (P-Karmali agar, 73.8%; unmodified Karmali agar,
      33.8%). Moreover, the selectivity of the P-Karmali agar was also better (P <
      0.05) than that of the other selective agar when comparing the number of
      contaminated plates (P-Karmali agar, 68.8%; unmodified Karmali agar, 87.5%) and
      growth index of competing flora (P-Karmali agar, 1.4; unmodified Karmali agar,
      2.7). The improved selective agar excluded competing flora resistant to
      antibiotic agents in unmodified Karmali agar, increasing isolation rate and
      selectivity for C. jejuni and C. coli.

PMID- 23550908
TI  - Correlating precursory declines in groundwater radon with earthquake magnitude.
AB  - Both studies at the Antung hot spring in eastern Taiwan and at the Paihe spring
      in southern Taiwan confirm that groundwater radon can be a consistent tracer for
      strain changes in the crust preceding an earthquake when observed in a low
      porosity fractured aquifer surrounded by a ductile formation. Recurrent anomalous
      declines in groundwater radon were observed at the Antung D1 monitoring well in
      eastern Taiwan prior to the five earthquakes of magnitude (Mw ): 6.8, 6.1, 5.9,
      5.4, and 5.0 that occurred on December 10, 2003; April 1, 2006; April 15, 2006;
      February 17, 2008; and July 12, 2011, respectively. For earthquakes occurring on
      the longitudinal valley fault in eastern Taiwan, the observed radon minima
      decrease as the earthquake magnitude increases. The above correlation has been
      proven to be useful for early warning local large earthquakes. In southern
      Taiwan, radon anomalous declines prior to the 2010 Mw 6.3 Jiasian, 2012 Mw 5.9
      Wutai, and 2012 ML 5.4 Kaohsiung earthquakes were also recorded at the Paihe
      spring. For earthquakes occurring on different faults in southern Taiwan, the
      correlation between the observed radon minima and the earthquake magnitude is not
      yet possible. 

PMID- 23550909
TI  - Probing hydrogen bond energies by mass spectrometry.
AB  - Mass spectrometry with desorption electrospray ionization (DESI) is demonstrated
      to be useful for probing the strength of hydrogen bonding, exemplified by various
      complexes of benzothiazoles and carboxylic acids in the solid state. Efficiencies
      for fragmentation of the complexes, quantified by collision-induced dissociation
      (CID) technology, correspond well with energies of the hydrogen bonds of O-H...N
      and N-H...O bridging each pair of benzothiazole and carboxylic acid. Linear
      correlations (with correlation factors of 0.8953 and 0.9928) have been
      established for the calibration curves of normalized collision energy at 100%
      fragmentation rate vs the length between donor and acceptor (in the hydrogen bond
      of O-H...N) as well as the slope of the fragmentation efficiency curve vs the
      average length difference between O-H...N and N-H...O in the complex. The
      mechanism responsible for determination of the hydrogen bonds is proposed on the
      basis of the experiments starting from the mixtures of the complexes as well as
      labeling with deuterium. As a complement of previously available methods (e.g., X
      ray diffraction analysis), expectably, the proposed mass spectrometric method
      seems to be versatile for probing hydrogen bond energies.

PMID- 23550910
TI  - Effect of a chlorhexidine-containing adhesive on dentin bond strength stability.
AB  - PURPOSE: The present study aimed to investigate a novel adhesive system
      containing 0.2% chlorhexidine digluconate (CHX) for its ability to improve the
      stability of the adhesive interface compared with the use of 2% CHX as a
      therapeutic primer. Furthermore, the study aimed to confirm the inhibitory
      properties of these CHX concentrations (0.2% and 2.0%) on dentin matrix
      metalloproteinase activity by gelatin zymography. METHODS: Superficial dentin
      substrate for bonding was obtained from 120 non-carious human molars. A
      conventional adhesive Peak LC Bond and a CHX-containing adhesive Peak Universal
      Bond were used either in combination with 35% phosphoric acid (etch-and-rinse
      approach) or with self-etching primer (self-etch approach) for evaluation of the
      variables CHX treatment (2.0% therapeutic primer and 0.2% adhesive), adhesive
      approach (etch-and-rinse and self-etch), and storage time (24 hours and six
      months). A bonding jig was used to fabricate composite cylinders, which were
      stored for either 24 hours or six months, after which shear bond strength (SBS)
      was evaluated using a notched-edge testing device. A three-way analysis of
      variance and a Student t-test with a significance level of p<0.05 were used to
      analyze the data. Extracts from concentrated demineralized human dentin powder
      were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and
      incubated in the presence of 0.2% and 2.0% CHX. RESULTS: No significant effect of
      CHX treatment, adhesive approach, storage time variables, or their interactions
      on mean SBS was demonstrated (p<0.05). No significant difference between the
      control and the CHX-treated groups was detected for either adhesive technique at
      24 hours or six months (p<0.05). No significant variation in mean SBS was
      detected after six months of storage (p<0.05). Zymographic analysis revealed
      bands of enzymatic activity for the group demineralized with phosphoric acid and
      complete inhibition of gelatinolytic activity for the groups treated with 0.2%
      and 2.0% CHX. CONCLUSIONS: CHX demonstrated inhibition of dentin proteolytic
      activity. However, when CHX was incorporated into a commercially available
      adhesive or used as a therapeutic primer, no difference in bond strength was
      observed at baseline or after six months of storage relative to the control group
      without CHX.

PMID- 23550911
TI  - Porcelain veneers as an alternative for esthetic treatment: clinical report.
AB  - This case report describes the restoration of the anterior dentition with
      porcelain laminate veneers. The advances in bonding of porcelain to tooth
      structure make this treatment a feasible alternative to restore teeth with
      alteration in shape and position in cases in which the esthetic demand is high.
      The rationale for various choices in this treatment protocol is detailed with
      reference to the pertinent literature. Thus, the clinical success of the
      technique depends on the correct identification of a case for which this
      treatment is appropriate and the successful execution of the clinical steps
      involved.

PMID- 23550912
TI  - Physical property evaluation of four composite materials.
AB  - PURPOSE: The purpose of this study was to evaluate the physical properties of
      current formulations of composite resins for polymerization shrinkage, surface
      hardness, and flexural strength. In addition, a comparison of Knoop and Vickers
      hardness tests was made to determine if there was a correlation in the precision
      between the two tests. MATERIALS AND METHODS: Four composite resin materials were
      used: Filtek LS (3M-ESPE), Aelite LS (Bisco), Kalore (GC America), and Empress
      Direct (Ivoclar). Ten samples of each composite (shade Vita A2) were used.
      Polymerization shrinkage was measured with the Kaman linometer using 2-mm-thick
      samples, cured for 40 seconds and measured with digital calipers for sample
      thickness. Surface microhardness samples were prepared (2-mm thick * 12-mm
      diameter) and sequentially polished using 600-grit silicone carbide paper, 9 MUm
      and 1 MUm diamond polishing solutions. After 24 hours of dry storage, Knoop (200
      g load, 15 seconds dwell time) and Vickers (500 g load, 15 seconds dwell time)
      hardness tests were conducted. Flexural strength test samples (25 * 2 * 2 mm)
      were stored in 100% relative humidity and analyzed using a three-point bending
      test with an Instron Universal Testing Machine (Instron 5565, Instron Corp)
      applied at a crosshead speed of 0.75 +/- 0.25 mm/min. Maximum load at fracture
      was recorded. One-way analysis of variance and Tukey multiple comparison tests
      were used to determine significant differences in physical properties among
      materials. RESULTS: Filtek LS had significantly lower shrinkage (0.45 [0.39]
      vol%). Aelite LS demonstrated the greatest Knoop surface hardness (114.55 [8.67]
      KHN), followed by Filtek LS, Kalore, and Empress Direct (36.59 [1.75] KHN).
      Vickers surface hardness was significantly greater for Aelite LS (126.88 [6.58]
      VH), followed by Filtek LS, Kalore, and Empress Direct (44.14 [1.02] VH).
      Flexural strength (MPa) was significantly higher for Aelite LS and Filtek LS
      (135.75 [17.35]; 129.42 [9.48]) than for Kalore and Empress Direct (86.84 [9.04];
      92.96 [9.27]). There is a strong correlation between results obtained using Knoop
      and Vickers hardness tests (r=0.99), although Vickers values were significantly
      greater for each material. CONCLUSION: Results suggest that Aelite LS possesses
      superior hardness and flexural strength, while Filtek LS has significantly less
      shrinkage compared with the other composites tested.

PMID- 23550913
TI  - The management of defective resin composite restorations: current trends in
      dental school teaching in Japan.
AB  - AIM: The aim of this article is to investigate the contemporary teaching of the
      management of defective direct resin composite restorations in dental schools in
      Japan. METHODS: A questionnaire relating to the teaching of the management of
      defective resin composite restorations was developed and e-mailed to 29 dental
      schools in Japan in 2010. RESULTS: Completed responses were received from 19 of
      the 29 invited schools (response rate = 66%). Eighteen schools (95%) report that
      they included the teaching of repair of direct defective resin composite
      restorations in their dental school programs. Thirteen schools reported that they
      included both clinical and didactic instruction on the repair of direct resin
      composite restorations. Fourteen schools did not teach any mechanical roughening
      of the exposed resin composite restoration surface before undertaking a repair.
      The most commonly reported treatment was acid etching with phosphoric acid (12
      schools). The most commonly taught material for completing repairs was a flowable
      resin composite (16 schools). CONCLUSION: The teaching of repair of defective
      resin composite restorations is well established within many Japanese dental
      schools, to a greater extent than in some other regions of the world. The impact
      of this teaching on subsequent clinical practices in Japan should be
      investigated. Furthermore, it is concluded that there is a need for much stronger
      leadership in operative and conservative dentistry, ideally at the global level,
      to resolve differences in key aspects of operative procedures such as repairs.

PMID- 23550914
TI  - Longevity of direct restorations in stress-bearing posterior cavities: a
      retrospective study.
AB  - The aims of this retrospective clinical study were to compare the longevities of
      direct posterior amalgam restorations (AMs) and resin composite restorations
      (RCs) that were subjected to occlusal stresses and to investigate variables
      predictive of their outcome. A total of 269 AMs and RCs filled in Class I and II
      cavities of posterior teeth were evaluated with Kaplan-Meier survival estimator
      and multivariate Cox proportional hazard model. Seventy-one retreated
      restorations were reviewed from dental records. The other 198 restorations still
      in use were evaluated according to modified US Public Health Service (USPHS)
      criteria by two investigators. The longevity of RCs was significantly lower than
      that of AMs (AM = 8.7 years and RC = 5.0 years, p<0.05), especially in molars.
      The prognostic variables, such as age, restorative material, tooth type, operator
      group, diagnosis, cavity classification, and gender, affected the longevity of
      the restorations (multivariate Cox regression analysis, p<0.05). However, among
      the restorations working in oral cavities, their clinical performance evaluated
      with modified USPHS criteria showed no statistical difference between both
      restoratives. In contrast to the short longevity of RCs relative to AMs, the
      clinical performance of RCs working in oral cavities was observed to be not
      different from that of AMs. This suggests that once a RC starts to fail, it
      happens in a rapid progression. As posterior esthetic restorations, RCs must be
      observed carefully with periodic follow-ups for early detection and timely repair
      of failures.

PMID- 23550915
TI  - Interfacial nanoleakage and bonding of self-adhesive systems cured with a
      modified-layering technique to dentin of weakened roots.
AB  - OBJECTIVE: The purpose of the study was to evaluate the nanoleakage and bond
      strength of different self adhesive systems cured with a modified-layering
      technique (MLT) to dentin of weakened roots. METHODS: Twenty-one maxillary
      incisors were decoronated and then root canals were instrumented and obturated
      with the cold lateral compaction technique. Weakened roots were simulated by
      flaring root canals until only 1 mm dentin thickness remained. Teeth were
      distributed into three groups. The canals were backfilled with Vertise Flow (VF
      group), a self-adhering system, following a modified-layering technique using two
      light-transmitting posts, sizes 6 and 3. DT Light Post size 2 was cemented using
      the same material. Remaining roots were prepared and cured in the same way as the
      VF group. However, in the TS/MF group, Clearfil Tri-S Bond (TS) adhesive and
      Clearfil Majesty Flow (MF) composite were used, while in the ED/PF group, ED
      primer II (ED)/Panavia F2.0 (PF) were used. After one week of storage, each root
      was sectioned to obtain six slices (two slices from each root third: coronal,
      middle and apical) of 0.9 +/- 0.1 mm thickness. Interfacial nanoleakage
      expression was analyzed using a field emission scanning electron microscope (FEG
      SEM), and the micro push-out bond strength (MUPOBS) was measured at different
      root regions. Modes of failure were also determined using SEM. Data were
      statistically analyzed using two-way analysis of variance with repeated measures
      and Tukey post hoc test (p<=0.05). RESULTS: With MLT, all adhesive systems showed
      nanoleakage. For MUPOBS, there was a statistically significant effect for
      adhesive systems (p<0.001) but not for root region (p<0.64) or for their
      interaction (p=0.99). Tukey post hoc test revealed that the bond strength of the
      VF group was significantly higher than the TS/MF and ED/PF groups for all root
      regions. CONCLUSION: All of the tested self-adhesive systems cured using MLT had
      slight nanoleakage and were not sensitive to root regional differences. Self
      adhering systems had higher bond strength than self-etch adhesives.

PMID- 23550916
TI  - Comparison of 24-hour intraocular pressure reduction obtained with
      brinzolamide/timolol or brimonidine/timolol fixed-combination adjunctive to
      travoprost therapy.
AB  - BACKGROUND: To determine the adjunctive 24-h efficacy obtained with
      brinzolamide/timolol, or brimonidine/timolol fixed combinations (FCs) in open
      angle glaucoma patients insufficiently controlled on travoprost monotherapy.
      METHODS: Prospective, observer-masked, active controlled, crossover, comparison.
      Qualified primary open-angle or exfoliative glaucoma patients with a baseline
      intraocular pressure (IOP) >18 mm Hg at 10:00 on travoprost monotherapy were
      randomized for 3 months to either brinzolamide/timolol, or brimonidine/timolol FC
      therapy adjunct to travoprost. Patients were then crossed-over to the opposite
      therapy for another 3 months. At baseline and at the end of each treatment
      period, the patients underwent 24-h IOP monitoring. RESULTS: Fifty patients
      completed the study. The mean 24-h baseline IOP on travoprost monotherapy was
      20.1 mm Hg [95% confidence interval (CI): 19.6, 20.7 mm Hg]. Both adjunctive FC
      therapies significantly reduced the IOP at each time point and for the mean 24-h
      IOP (P<0.001) compared with travoprost monotherapy. Brinzolamide/timolol FC
      provided a significantly lower mean 24-h IOP (17.2 mm Hg, 95% CI: 16.4, 17.9 mm
      Hg) than brimonidine/timolol FC (18.0 mm Hg, 95% CI: 17.3, 18.8 mm Hg) (P<0.001).
      For all the 3 timepoints between 18:00 and 02:00, the brinzolamide/timolol FC
      provided a significantly lower IOP than the brimonidine/timolol FC (P<=0.036).
      For the other 3 timepoints, no significant differences were detected.
      CONCLUSIONS: This study demonstrated that both FCs provide statistically and
      clinically significant incremental 24-h IOP lowering to travoprost monotherapy.
      The brinzolamide/timolol FC however achieves a better mean 24-h IOP control owing
      to the greater efficacy in late afternoon and during the night.

PMID- 23550918
TI  - Acute alcohol produces ataxia and cognitive impairments in aged animals: a
      comparison between young adult and aged rats.
AB  - BACKGROUND: Aging in both humans and rodents appears to be accompanied by
      physiological changes that increase biologic sensitivity to ethanol (EtOH)
      intoxication. However, animal models designed to investigate this increased
      alcohol sensitivity have yet to be established. For this reason, we sought to
      determine whether acute EtOH administration produces differential effects on
      motor coordination and spatial cognition in young adult and aged rats. METHODS:
      Male young adult (postnatal day 70 to 72) and aged (~18 months) Sprague-Dawley
      rats were assessed on 2 motor tasks (the accelerating rotarod [RR] and the aerial
      righting reflex [ARR]) and a single cognitive performance task (the Morris water
      maze [MWM]). Following acute EtOH exposure via intraperitoneal injection,
      animals' performance was reassessed. RESULTS: Aged rats showed a dramatic
      increase in EtOH-induced ataxia on the RR and the ARR relative to young adult
      animals. Similarly, results from the MWM revealed that aged animals had slightly
      greater EtOH-induced impairments compared with young adult animals. Importantly,
      the increased impairments produced by EtOH were not due to differential blood
      EtOH levels. CONCLUSIONS: We demonstrate for the first time that aged rats show
      greater EtOH-induced deficits compared with young adults in tasks of motor and
      cognitive performance. The possible role of protein kinase C as a mechanism for
      increased sensitivity to the motor-impairing effects of EtOH is discussed. Given
      the high prevalence of alcohol use among the elderly, increased vulnerability to
      alcohol-induced deficits may have a profound effect on injury in this population.

PMID- 23550917
TI  - Allenamides: a powerful and versatile building block in organic synthesis.

PMID- 23550919
TI  - Gender differences in quality of life following subthalamic stimulation for
      Parkinson's disease.
AB  - OBJECTIVES: Surveys of subthalamic nucleus (STN) deep brain stimulation (DBS) for
      Parkinson's disease (PD) have shown that this procedure is roughly twice more
      common in men than in women. Here, we investigate possible differences between
      women and men undergoing STN DBS, with respect to health-related quality of life.
      MATERIALS AND METHODS: Forty-nine consecutive patients (18 women) received STN
      DBS. The impact of PD and its surgical treatment was compared between women and
      men, before and at mean of 19 +/- 11 months after surgery, using the Unified
      Parkinson Disease Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire
      39 (PDQ-39). RESULTS: Duration of disease at surgery and off-medication scores of
      the motor part of the UPDRS were similar in women and men. At baseline, women had
      lower doses of dopaminergic medication than men, experienced more disability due
      to dyskinesias, had more sensory symptoms and perceived more difficulties in
      mobility. Following DBS, both men and women showed equal and significant (P <
      0.001) improvement in off-medication scores on the UPDRS III. On the PDQ-39,
      women expressed improvement in ADL to a greater extent than men. Moreover, women
      but not men showed a positive effect on mobility, stigma and cognition as well as
      on the summary score of PDQ-39. CONCLUSIONS: Although STN DBS results in equal
      degree of motor improvement between women and men, health-related quality of life
      seems to improve to a greater extent in women.

PMID- 23550920
TI  - The effect of genetic admixture in an association study: genetic polymorphisms
      and chromosome aberrations in a Colombian population exposed to organic solvents.
AB  - The human population is heterogeneous in genetic susceptibility, chromosomal
      instability and disease risk; all factors which depend on inherited genetic
      constitution and acquired nongenetic environmental and occupational factors.
      Recently, special attention has been directed to the identification of sources of
      potential bias in population studies of gene-environment interactions including
      genetic admixture. The aim of this study was to evaluate the effect of genetic
      admixture in the association of genetic polymorphisms and chromosome aberrations
      (CA) in a population exposed to organic solvents. We assessed genetic admixture
      via 34 genetic ancestry informative markers (AIMs) in 398 Colombian individuals.
      We report a statistically significant difference of higher CA frequency in
      individuals' below-average European component, and in individuals' above-average
      Native American component after adjusting for covariates. In addition, the
      confounding risk ratio values are >=10% than the adjusted risk ratio, suggesting
      that population stratification is a confounding factor in this gene-environment
      association study. Furthermore, after adjusting for individual admixture
      proportions and covariates, the results demonstrate that glutathione-S
      transferase M1 (GSTM1)-null is associated with CA frequency increase. These
      results suggest that gene-environment association studies that involve recently
      admixed populations should take into consideration population stratification as a
      confounding factor and suggest GSTM1-null as a genetic marker associated with CA
      frequency increase. 

PMID- 23550921
TI  - alpha-Amylase is a potential growth inhibitor of Porphyromonas gingivalis, a
      periodontal pathogenic bacterium.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is a major etiological agent
      in the development and progression of periodontal diseases. In this study, we
      isolated a cell growth inhibitor against P. gingivalis species from rice protein
      extract. MATERIAL AND METHODS: The cell growth inhibitor active against P.
      gingivalis was purified from polished rice extract using a six-step column
      chromatography process. Its antimicrobial properties were investigated through
      microscope analysis, spectrum of activity and general structure. RESULTS: The
      inhibitor was identified as AmyI-1, an alpha-amylase, and showed significant cell
      growth inhibitory activity against P. gingivalis species. Scanning electron
      microscopy micrograph analysis and bactericidal assay indicated an intriguing
      possibility that the inhibitor compromises the cell membrane structure of the
      bacterial cells and leads to cell death. Moreover, alpha-amylases from human
      saliva and porcine pancreas showed inhibitory activity similar to that of AmyI-1.
      CONCLUSIONS: This is the first study to report that alpha-amylases cause cell
      death of periodontal pathogenic bacteria. This finding highlights the potential
      importance and therapeutic potential of alpha-amylases in treating periodontal
      diseases.

PMID- 23550922
TI  - Validation of a method for the determination of aminoglycosides in different
      matrices and species based on an in-house concept.
AB  - A simple, rapid, and sensitive method for the determination and confirmation of
      the aminoglycosides streptomycin, dihydrostreptomycin, spectinomycin, apramycin,
      kanamycin, paromomycin, gentamicin and neomycin in cow's milk as well as in
      bovine and porcine muscle and kidney was developed. Validation was performed on
      the basis of an in-house concept with different factor-level combinations in
      accordance with Commission Decision 2002/657/EC. After extraction with
      trichloroacetic acid solution, clean-up was performed by way of SPE. LC-MS/MS
      analysis was carried out by means of an HILIC column for the separation of the
      analytes, and by using MS/MS in positive ESI mode to measure the transitions of
      the substances in MRM mode. For quantification, matrix calibration curves in the
      linear range around the MRLs as well as the internal standard tobramycin were
      used. The calculated validation parameters like CCalpha, CCbeta, recovery (94
      103%), relative repeatability RSDr (3.6-9.7%), and relative within-laboratory
      reproducibility RSDwR (4.6-10.0%) fulfilled the requirements of Commission
      Decision 2002/657/EC. 

PMID- 23550923
TI  - Wild rodents as a model to discover genes and pathways underlying natural
      variation in infectious disease susceptibility.
AB  - Individuals vary in their susceptibility to infectious disease, and it is now
      well established that host genetic factors form a major component of this
      variation. The discovery of genes underlying susceptibility has the potential to
      lead to improved disease control, through the identification and management of
      vulnerable individuals and the discovery of novel therapeutic targets. Laboratory
      rodents have proved invaluable for ascertaining the function of genes involved in
      immunity to infection. However, these captive animals experience conditions very
      different to the natural environment, lacking the genetic diversity and
      environmental pressures characteristic of natural populations, including those of
      humans. It has therefore often proved difficult to translate basic laboratory
      research to the real world. In order to further our understanding of the genetic
      basis of infectious disease resistance, and the evolutionary forces that drive
      variation in susceptibility, we propose that genetic research traditionally
      conducted on laboratory animals is expanded to the more ecologically valid arena
      of natural populations. In this article, we highlight the potential of using wild
      rodents as a new resource for biomedical research, to link the functional genetic
      knowledge gained from laboratory rodents with the variation in infectious disease
      susceptibility observed in humans and other natural populations.

PMID- 23550924
TI  - Comments on 'Effect of pioglitazone on testosterone in eugonadal men with type 2
      diabetes mellitus: a randomized double-blind placebo controlled study'.

PMID- 23550925
TI  - Predicting treatment response in psoriasis using serum levels of adalimumab and
      etanercept: a single-centre, cohort study.
AB  - BACKGROUND: A substantial proportion of patients with psoriasis do not respond,
      or lose initial response to tumour necrosis factor-alpha antagonists. One
      possible mechanism relates to subtherapeutic drug levels due to an immunogenic
      antibody response. OBJECTIVES: To investigate the association between serum
      adalimumab and etanercept levels, antidrug antibody levels and clinical response
      in a cohort of patients with psoriasis using a commercially available enzyme
      linked immunoassay. METHODS: In a single-centre cohort of 56 adults with chronic
      plaque psoriasis initiated on adalimumab or etanercept monotherapy between 2009
      and 2011, drug and antidrug antibody levels were measured at the patients'
      routine clinic reviews (4, 12 and 24 weeks of treatment and the last available
      observation). Patients' responses at 6 months were stratified into responders
      [75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) or
      Physician's Global Assessment score of 'clear' or 'nearly clear'] and
      nonresponders (failure to achieve PASI 50). RESULTS: After 4 weeks, adalimumab
      levels were significantly higher in responders compared with nonresponders (P =
      0.003) and these higher levels were sustained at 12 and 24 weeks. Anti adalimumab
      antibodies were detected in 25% of nonresponders (two of eight patients, average
      22.5 weeks' follow-up) and none of the responders (n = 23, average 26.1 weeks'
      follow-up). There was no significant association between etanercept levels and
      clinical response at 4 weeks (P = 0.317) and no antietanercept antibodies were
      detected. Lack of serum trough levels may have resulted in underestimation of the
      prevalence of antidrug antibodies. CONCLUSIONS: Early adalimumab drug level
      monitoring at 4 weeks may be useful in predicting treatment response and
      potentially reduce drug exposure (and associated cost) with earlier review of
      treatment in those with low levels. No conclusions about the value of etanercept
      drug monitoring can be made due to the paucity of data. Larger studies are now
      required to assess the clinical utility and cost-effectiveness of these assays in
      personalizing therapy in psoriasis.

PMID- 23550926
TI  - Challenges in monitoring and maintaining the health of pilots engaged in
      telewarfare.

PMID- 23550927
TI  - Mental health diagnoses and counseling among pilots of remotely piloted aircraft
      in the United States Air Force.
AB  - Remotely piloted aircraft (RPA), also known as drones, have been used extensively
      in the recent conflicts in Iraq and Afghanistan. Although RPA pilots in the U.S.
      Air Force (USAF) have reported high levels of stress and fatigue, rates of mental
      health (MH) diagnoses and counseling in this population are unknown. We
      calculated incidence rates of 12 specific MH outcomes among all active component
      USAF RPA pilots between 1 October 2003 and 31 December 2011, and by various
      demographic and military variables. We compared these rates to those among all
      active component USAF manned aircraft (MA) pilots deployed to Iraq/Afghanistan
      during the same period. The unadjusted incidence rates of all MH outcomes among
      RPA pilots (n=709) and MA pilots (n=5,256) were 25.0 per 1,000 person-years and
      15.9 per 1,000 person-years, respectively (adjusted incidence rate ratio=1.1, 95%
      confidence interval=0.9-1.5; adjusted for age, number of deployments, time in
      service, and history of any MH outcome). Th ere was no significant difference in
      the rates of MH diagnoses, including post-traumatic stress disorder, depressive
      disorders, and anxiety disorders between RPA and MA pilots. Military policymakers
      and clinicians should recognize that RPA and MA pilots have similar MH risk
      profiles.

PMID- 23550928
TI  - External causes of traumatic brain injury, 2000-2011.
AB  - This report summarizes frequencies, distributions, and trends of external causes
      of traumatic brain injuries (TBIs) that are recorded on standardized records of
      medical encounters of U.S. military members. Causes of TBI were reported for 100
      percent of cases hospitalized in military facilities, but were relatively
      infrequently reported in other treatment settings (i.e., military outpatient
      facilities, combat theater and civilian medical facilities). During 2008-2011 in
      all clinical settings combined, 24,115 service members had TBI case-defining
      medical encounters with recorded injury causes. Accidents represented 74 percent
      of recorded causes; the most frequently reported specific causes were motor
      vehicle traffic accidents (20%), falls (20%), and being struck by or struck
      against an object (15%). Similar proportions of TBIs were reportedly due to
      intentional "assaults" unrelated to war (11%) and "battle injuries" (11%).
      Assaults were second only to motor vehicle accidents as reported causes of TBIs
      treated in civilian hospitals. Some TBIs reportedly due to accidents with
      guns/explosives were likely combat injuries that were miscoded in military
      hospitals. The doubling of the number of combat-related TBIs reported from
      Iraq/Afghanistan between 2010 and 2011 undoubtedly reflects the U.S. military's
      increased focus on identifying and treating TBIs among deployed military members.

PMID- 23550929
TI  - Mid-season influenza vaccine effectiveness for the 2012-2013 influenza season.

PMID- 23550930
TI  - Update: Heat injuries, active component, U.S. Armed Forces, 2012.
AB  - In 2012, there were more active component service members treated for heat stroke
      (n=365) than in 2011 but fewer than in 2008 or 2009. Compared to their respective
      counterparts, incidence rates of heat stroke were higher among males, those
      younger than 20 years of age, Marine Corps and Army members, recruit trainees,
      and service members in combat-specific occupations. Fewer service members were
      treated for "other heat injuries" in 2012 (n=2,257) than in 2010 or 2011; also,
      there were fewer hospitalizations for "other heat injuries" in 2012 than in any
      of the prior four years. The incidence rate of "other heat injuries" was higher
      among females than males, more than 8 times higher among recruit trainees than
      other enlisted members, and 20 times higher among recruit trainees than officers.
      From 2008 to 2012, 1,060 heat injury events occurred in Iraq/Afghanistan; 6.5
      percent (n=69) were due to heat stroke.

PMID- 23550931
TI  - Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces 2008-2012.
AB  - In 2012, there were 402 incident episodes of rhabdomyolysis likely due to
      physical exertion and/or heat stress ("exertional rhabdomyolysis") among U.S.
      service members. The annual rates of exertional rhabdomyolysis increased 30
      percent from 2008 to 2012. Th e highest incidence rates occurred in males, black,
      non-Hispanic service members, service members younger than 20 years of age,
      members of the Army and Marine Corps, recruit trainees, and those in combat
      specific occupations. Incidence rates were higher among service members with
      homes of record from the Northeast compared to other regions of the U.S. Most
      cases were diagnosed at installations that support basic combat/recruit training
      or major Army or Marine Corps ground combat units. Medical care providers should
      consider exertional rhabdomyolysis in the differential diagnosis when service
      members - particularly recruits - present with muscular pain and swelling,
      limited range of motion, and/or the excretion of dark urine (e.g., myoglobinuria)
      after strenuous physical activity, particularly in hot, humid weather.

PMID- 23550932
TI  - Update: Exertional hyponatremia, active component, U.S. Armed Forces, 1999-2012.
AB  - From 1999 through 2012, there were 1,333 incident diagnoses of exertional
      hyponatremia among active component members of the U.S. Armed Forces. Annual
      incidence rates rose sharply from 2008 to 2010 but have since decreased by 50
      percent from 2010 to 2012. In 2012, there were fewer incident cases (n=84) than
      in any of the previous six years. The recent decrease in rates overall reflects
      sharply declining rates in the Marine Corps and slight decreases in the other
      services. Relative to their respective counterparts, crude incidence rates of
      exertional hyponatremia for the entire 14 year surveillance period were higher
      among females, those in the youngest age group, Marines, recruit trainees, and
      "other" military occupations. Service members (particularly recruit trainees) and
      their supervisors must be vigilant for early signs of heat-related illnesses and
      must be knowledgeable of the dangers of excessive water consumption and the
      prescribed limits for water intake during prolonged physical activity - e.g.,
      field training exercises, personal fitness training, recreational activities - in
      hot, humid weather.

PMID- 23550933
TI  - Development of latent fingerprints on thermal paper by the controlled application
      of heat.
AB  - Apparatus to produce a spatially and temporally uniform heat source is described
      and this is used to visualize latent fingerprints deposited onto thermal paper by
      raising the temperature of the paper. Results show an improvement over previous
      research when fingerprint deposits are aged or the developed fingerprints faint;
      visualization being enhanced by the use of a blue LED light source of 465 nm peak
      wavelength. An investigation of the components in fingerprint sweat likely to
      affect the solubility and hence color change of the dye present in the thermal
      paper has shown that polar protic solvents able to donate a proton are favored
      and a polar amino acid found commonly in eccrine fingerprint sweat (lysine) has
      been shown able to produce the desired color change. Aged fingerprint deposits on
      thermal paper from a variety of sources up to 4 years old have been visualized
      with this technique.

PMID- 23550934
TI  - Early onset absence epilepsy: what changes using Panayiotopoulos's criteria?

PMID- 23550935
TI  - In search of the Rosetta Stone for ESES.

PMID- 23550936
TI  - The way out of Babel.

PMID- 23550937
TI  - Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that
      mediate anticancer properties.
AB  - Curcumin is a biologically active component of curry powder. A structurally
      related class of mimetics possesses similar anti-inflammatory and anticancer
      properties. Mechanism has been examined by exploring kinase inhibition trends. In
      a screen of 50 kinases relevant to many forms of cancer, one member of the series
      (4, EF31) showed >=85% inhibition for 10 of the enzymes at 5 MUM, while 22 of the
      proteins were blocked at >=40%. IC50 values for an expanded set of curcumin
      analogues established a rank order of potencies, and analyses of IKKbeta and AKT2
      enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition
      dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases.
      Both selectivity and potency trends are compatible with protein sequence
      comparisons, while modeled kinase binding site geometries deliver a reasonable
      correlation with mixed inhibition. Overall, these analogues are shown to be
      pleiotropic inhibitors that operate at multiple points along cell signaling
      pathways.

PMID- 23550939
TI  - Modeling poliovirus risks and the legacy of polio eradication.
AB  - This introduction to the special issue on modeling poliovirus risks provides
      context about historical efforts to manage polioviruses and reviews the insights
      from models developed to support risk management and policy development.
      Following an overview of the contents of the special issue, the introduction
      explores the road ahead and offers perspective on the legacy of polio
      eradication.

PMID- 23550940
TI  - Lanthanide single-molecule magnets.

PMID- 23550938
TI  - Microdosing and drug development: past, present and future.
AB  - INTRODUCTION: Microdosing is an approach to early drug development where
      exploratory pharmacokinetic data are acquired in humans using inherently safe sub
      pharmacologic doses of drug. The first publication of microdose data was 10 years
      ago and this review comprehensively explores the microdose concept from
      conception, over the past decade, up until the current date. AREAS COVERED: The
      authors define and distinguish the concept of microdosing from similar
      approaches. The authors review the ability of microdosing to provide exploratory
      pharmacokinetics (concentration-time data) but exclude microdosing using positron
      emission tomography. The article provides a comprehensive review of data within
      the peer-reviewed literature as well as the latest applications and a look into
      the future, towards where microdosing may be headed. EXPERT OPINION: Evidence so
      far suggests that microdosing may be a better predictive tool of human
      pharmacokinetics than alternative methods and combination with physiologically
      based modelling may lead to much more reliable predictions in the future. The
      concept has also been applied to drug-drug interactions, polymorphism and
      assessing drug concentrations over time at its site of action. Microdosing may
      yet have more to offer in unanticipated directions and provide benefits that have
      not been fully realised to date.

PMID- 23550941
TI  - The value of crime scene and site visitation by forensic psychologists and
      psychiatrists.
AB  - Site visits and crime scene visitation by forensic psychologists and
      psychiatrists may enhance the accuracy and credibility of their forensic work in
      criminal, civil, and other important contexts. This ethically sound technique of
      after-the-fact data collection and verification offers numerous potential
      benefits to the forensic mental health professional: clarifying the subject's
      actions, assessing the reliability of witness reports, identifying contextual
      determinants of behavior, and more fully illuminating subject motivation and
      decision-making. Limitations and suggested guidelines for conducting site visits
      are offered. Guidelines include preplanning, arranging for an informed guide to
      accompany and narrate the visit, and conducting the site visit prior to forensic
      examinations.

PMID- 23550942
TI  - Dominant role of molybdenum in the electrochemical deposition of biological
      macromolecules on metallic surfaces.
AB  - The corrosion of CoCrMo, an alloy frequently used in orthopedic implants, was
      studied with an electrochemical quartz crystal microbalance (QCM) in three
      physiologically relevant solutions. Mass changes were measured during
      potentiodynamic tests, showing material deposition in protein solutions at
      potential levels that caused mass loss when the proteins were not present. X-ray
      photoelectron spectroscopy (XPS) data indicated that the deposited material was
      primarily organic and therefore was most likely derived from proteins in the
      electrolyte. Material deposition consistently occurred at a critical potential
      and was not dependent on the current density or total charge released into
      solution. Corrosion studies on pure Co, Cr, and Mo in protein solutions found
      material deposition only on Mo. We hypothesize that organic deposition results
      from the interaction of Mo(VI) with proteins in the surrounding solution. The
      organic layer is reminiscent of tribochemical reaction layers that form on the
      surface of CoCrMo hip bearings, suggesting that these types of layers can be
      formed by purely electrochemical means.

PMID- 23550943
TI  - Low ozone over Southern Australia in August 2011 and its impact on solar
      ultraviolet radiation levels.
AB  - During August 2011 stratospheric ozone over much of Southern Australia dropped to
      very low levels (approximately 265 Dobson Units) for over a week above major
      population centers. The weather during this low ozone period was mostly clear and
      sunny, resulting in measured solar ultraviolet radiation (UVR) levels up to 40%
      higher than normal, with UV Index > 3 despite being winter. Satellite ozone
      measurements and meteorological assimilated data indicate that the event was
      likely due in large part to the anomalous southward movement over Australia of
      ozone-poor air in the lower stratosphere originating from tropical latitudes. At
      the time, a study measuring the UVR exposures of outdoor workers in Victoria was
      underway and a number of the workers recorded substantial UVR exposures and were
      sunburnt. Given the cities and populations involved (approximately 10 million
      people), it is likely that many people could have been exposed to anomalously
      high levels of solar UVR for that time of year, with resultant higher UVR
      exposures and sunburns to unacclimatized skin (often a problem transitioning from
      low winter to higher spring UVR levels). Reporting procedures have been modified
      to utilize ozone forecasts to warn the public of anomalously high UVR levels in
      the future. 

PMID- 23550944
TI  - 3-year-old children make relevance inferences in indirect verbal communication.
AB  - Three studies investigated 3-year-old children's ability to determine a speaker's
      communicative intent when the speaker's overt utterance related to that intent
      only indirectly. Studies 1 and 2 examined children's comprehension of indirectly
      stated requests (e.g., "I find Xs good" can imply, in context, a request for X; N
      = 32). Study 3 investigated 3- and 4-year-old children's and adults' (N = 52)
      comprehension of the implications of a speaker responding to an offer by
      mentioning an action's fulfilled or unfulfilled precondition (e.g., responding to
      an offer of cereal by stating that we have no milk implies rejection of the
      cereal). In all studies, 3-year-old children were able to make the relevance
      inference necessary to integrate utterances meaningfully into the ongoing
      context.

PMID- 23550945
TI  - A preliminary randomised double-blind placebo-controlled clinical trial of
      hydroxyzine for treating sleep bruxism in children.
AB  - This is a randomised placebo-controlled clinical trial investigating the efficacy
      of hydroxyzine for treating parent-reported sleep bruxism in children.
      Participants of this trial were 30 patients randomly allocated to one of the two
      groups in a ratio of 1:2. One group received hydroxyzine and the other group
      received placebo. The outcome measures were Visual Analogue Scale test and
      Clinical Global Severity scale. Assessments occurred at baseline and at the end
      of week 4. The side effects of drugs were assessed using a checklist. The number
      of children in the hydroxyzine and placebo groups was 21 and 9, respectively. The
      mean age of children in the hydroxyzine and placebo groups was 8.4(s.d. = 3.3)
      and 6.5(s.d. = 1.5) years, respectively. Hydroxyzine more than placebo decreased
      bruxism score (3.8 versus 2.2). No serious adverse effect was reported. Current
      evidence support that hydroxyzine is effective and well tolerated for treating
      bruxism in children.

PMID- 23550946
TI  - Reproductive choices.

PMID- 23550947
TI  - Seeking maternal care at times of conflict: the case of Lebanon.
AB  - Providing quality maternity care within the emergency care packages for
      internally displaced populations in war-affected areas is somewhat challenging,
      although very essential. In this retrospective study, we describe the experiences
      and health care seeking behaviors of 1,015 pregnant and postpartum women during
      the 2006 war in Lebanon. Women reported interruptions in regular maternity care
      and experienced more complications during this period. Availability of health
      services and experiences of complications were the most important determinants of
      health care seeking behaviors. Maternal health services should be a part of any
      comprehensive emergency responsiveness plan, catering to women's needs in war
      affected areas.

PMID- 23550948
TI  - Translating knowledge directly to childbearing women: a study of Canadian women's
      preferences.
AB  - Knowledge translation has relied on research products that take years to
      disseminate, losing relevance for intended users. We used a mixed-methods
      approach to determine women's preferences for research results and format,
      intention to share results, and potential benefits. We sampled healthy, pregnant
      women who completed survey data during their third trimesters and wanted access
      to results. Mothers preferred results about sleep, fears, and anxieties during
      later pregnancy to benefit from reassurance that their experiences were shared.
      Women mostly intended to share results with their social networks. Organizational
      contacts increased dissemination of the women's preferred information to nonstudy
      participants.

PMID- 23550949
TI  - Pregnancy experiences of Western Australian women attending a specialist
      childbirth and mental illness antenatal clinic.
AB  - Our purpose was to explore the pregnancy experiences of Australian women
      attending a specialized childbirth and mental illness (CAMI) antenatal clinic. A
      qualitative exploratory design was selected to give voice to women with severe
      mental illness receiving antenatal care. Telephone interviews with 41 women, 24
      primiparous and 17 multiparous, were analyzed using thematic analysis. Three
      themes emerged: "building relationships," "acknowledging me as a person with
      special needs," and "respecting and understanding without stigma." Findings offer
      insight into care experiences possible within a multidisciplinary model developed
      to address psychiatric and obstetric needs of pregnant women with severe mental
      illness.

PMID- 23550950
TI  - A qualitative study on the food habits and related beliefs of pregnant British
      Bangladeshis.
AB  - It is quite challenging to deal with the health care needs of migrant populations
      in general, especially pregnant women, due to their diverse sociopolitical and
      cultural beliefs and practices. In this article, we aim to examine and understand
      the food habits and beliefs of pregnant British Bangladeshis using qualitative
      methods. Our results indicate some positive associations between the increased
      intakes of particular foods to ensure healthy outcomes. We also note that
      migration affects pregnant Bangladeshi women's physical and mental conditions. We
      conclude that effective health care and awareness about traditional food beliefs
      and habits, and their subsequent reflection into the national and local policy
      agendas, may bring forth positive changes and improve the overall health of
      pregnant women.

PMID- 23550951
TI  - Theoretical exploration of the mechanism of riboflavin formation from 6,7
      dimethyl-8-ribityllumazine: nucleophilic catalysis, hydride transfer, hydrogen
      atom transfer, or nucleophilic addition?
AB  - The cofactor riboflavin is biochemically synthesized by a constitutionally
      intricate process in which two molecules of 6,7-dimethyl-8-ribityllumazine react
      with each other to form one molecule of the cofactor and one molecule of 5-amino
      6-(ribitylamino)uracil. Remarkably, this complex molecular transformation also
      proceeds non-enzymatically in boiling aqueous solution at pH 7.3. Four different
      mechanistic pathways for this transformation (nucleophilic catalysis, hydride
      transfer, hydrogen atom transfer, and a nucleophilic addition mechanism) have now
      been analyzed by density functional theory [M06-2X/def2-TZVPP/CPCM//M06-2X/6
      31+G(d,p)/IEFPCM]. On the basis of these computational results, a so far
      unpublished nucleophilic addition mechanism is the lowest energy pathway yielding
      riboflavin. The previously proposed mechanism involving nucleophilic catalysis is
      higher in energy but is still a viable alternative for an enzyme-catalyzed
      process assisted by suitably positioned catalytic groups. Pathways involving the
      transfer of a hydride ion or of a hydrogen atom are predicted to proceed through
      higher energy transition states and intermediates.

PMID- 23550952
TI  - Effects of fulvic acid on uranium(VI) sorption kinetics.
AB  - This study focuses on the effects of fulvic acid (FA) on uranium(VI) sorption
      kinetics to a silica sand. Using a tritium-labeled FA in batch experiments made
      it possible to investigate sorption rates over a wide range of environmentally
      relevant FA concentrations (0.37-23 mg L(-1) TOC). Equilibrium speciation
      calculations were coupled with an evaluation of U(VI) and FA sorption rates based
      on characteristic times. This allowed us to suggest plausible sorption mechanisms
      as a function of solution conditions (e.g., pH, U(VI)/FA/surface site ratios).
      Our results indicate that U(VI) sorption onto silica sand can be either slower or
      faster in the presence of FA compared to a ligand-free system. This suggests a
      shift in the underlying mechanisms of FA effects on U(VI) sorption, from
      competitive sorption to influences of U(VI)-FA complexes, in the same system.
      Changes in metal sorption rates depend on the relative concentrations of metals,
      organic ligands, and mineral surface sites. Hence, these results elucidate the
      sometimes conflicting information in the literature about the influence of
      organic matter on metal sorption rates. Furthermore, they provide guidance for
      the selection of appropriate sorption equilibration times for experiments that
      are designed to determine metal distribution coefficients (Kd values) under
      equilibrium conditions.

PMID- 23550953
TI  - 'Pin-point precision' for pexing sutures.

PMID- 23550954
TI  - Performance on Paced Auditory Serial Addition Test and cerebral blood flow in
      multiple sclerosis.
AB  - BACKGROUND: To assess the relationship between performance on the Paced Auditory
      Serial Addition Test (PASAT) and both cerebral blood flow (CBF) and axonal
      metabolic integrity in normal appearing white matter (NAWM) of the centrum
      semiovale in patients with multiple sclerosis (MS). METHODS: Normal appearing
      white matter of the centrum semiovale was investigated with magnetic resonance
      (MR) imaging in 28 non-depressed individuals (18 patients with MS and 10 healthy
      controls). CBF was assessed with pseudo-continuous arterial spin labeling. N
      acetylacetate/creatine (NAA/Cr) ratios (a metabolic axonal marker) were measured
      using (1) H-MR spectroscopy. CBF was also measured in frontoparietal cortices and
      cerebellar hemispheres. RESULTS: In subjects with MS, we found a positive
      correlation between performance on the PASAT and CBF to the left centrum
      semiovale (P = 0.008), but not with the NAA/Cr ratio. There were no correlations
      between PASAT scores and CBF to the right centrum semiovale, frontoparietal
      cortices, and cerebellar hemispheres. There was no correlation between PASAT
      scores and NAA/Cr ratios. CONCLUSIONS: Our preliminary results suggest that
      performance on the PASAT in subjects with MS correlates with CBF to the left
      centrum semiovale, which contains left frontoparietal white matter association
      tracts involved in information processing speed and working memory.

PMID- 23550955
TI  - Beneficial effects of adequate iodine supply on characteristics of thyroid
      autonomy.
AB  - OBJECTIVE: Our aim was to establish the characteristics of thyroid autonomy (TA)
      in Slovenian patients and the required therapeutic dose of radioiodine before and
      ten years after the increase in mandatory salt iodization from previous 10 mg of
      potassium iodide to 25 mg per kg in 1999 because almost no data about TA and
      radioiodine treatment with respect to iodine supply are available. DESIGN:
      Retrospective clinical study. PATIENTS: We reviewed records of all patients
      referred for the first time in 1998 and 2009 to the Thyroid Department at the
      University Medical Centre Ljubljana which is a tertiary referral centre with a
      stable catchment area for more than 20 years. METHODS: TA was diagnosed by
      thyroid function, ultrasound, scintigraphy and negative TSH receptor antibodies.
      Demographic characteristics and the applied dose of radioiodine were evaluated.
      RESULTS: In 1998, significantly more patients presented with TA than in 2009 (383
      of 3243, 11.8% and 333 of 4546, 7.3%, respectively, P < 0.001). In 1998, the
      ratio between hyperthyroid and euthyroid patients was higher than in 2009 (6:1
      and 2.1:1, respectively, P < 0.001). In 1998, patients were younger than in 2009
      (mean 63.8 +/- 13.9 and 66.8 +/- 14.9 years, respectively, P < 0.004).
      Hyperthyroid patients were older than euthyroid in both years (P < 0.001). In
      1998, mean applied dose of radioiodine was significantly lower than in 2009 (713
      +/- 306 and 791 +/- 194 MBq, respectively, P = 0.003). CONCLUSIONS: In adequate
      iodine supply, TA is less frequent, patients are less often hyperthyroid, they
      are older and cured with higher doses of radioiodine than in mild iodine
      deficiency.

PMID- 23550956
TI  - Novel RHD alleles with weak hemagglutination and genetic Exon 9 diversity: weak D
      Types 45.1, 75, and 76.
AB  - BACKGROUND: Molecular variant RHD allele analysis is best complemented by
      detailed characterization of the associated D phenotype. STUDY DESIGN AND
      METHODS: Variant D types were characterized using molecular typing, RHD
      sequencing, extended serologic D antigen investigations, and flow cytometric D
      antigen quantification. RESULTS: We discovered three novel weak D types termed
      weak D Types 45.1, 75, and 76 with RHD nucleotide substitutions coding for amino
      acid exchanges in predicted intracellular RhD polypeptide stretches; antigen
      densities of approximately 1.990, 900, and 240 D sites per red blood cell were
      found, respectively. Adsorption-elution technique-supported D epitope mapping of
      these three weak D types demonstrated the expression of all tested D epitopes.
      Initial molecular typing of the three investigated samples by RHD gene exon
      scanning polymerase chain reaction using sequence-specific priming yielded a
      negative reaction for A1193 located in RHD Exon 9 and could be explained by
      specific mutations for weak D Types 45.1 (C818T, G1195A), 75 (G1194C), and 76
      (A1215C). CONCLUSION: All novel weak D types expressed all tested D epitopes. It
      is of interest that for weak D Types 45.1, 75, and 76, similar alleles with a
      maximal divergence of one amino acid only, that is, weak D Types 45, 41, and 68,
      respectively, have been reported so far.

PMID- 23550957
TI  - Rapid reduction in the incidence of cancer of unknown primary. A population-based
      study.
AB  - BACKGROUND: Cancer of unknown primary (CUP) carries a dismal prognosis due to the
      two hallmarks of 1) being metastatic with 2) no known specific treatment. An
      organ-labeled diagnosis of cancer should therefore be sought. In this study, we
      have analyzed population-based incidence and survival data of CUP over the latest
      40 years. MATERIAL AND METHODS: Complete national data on 23 004 CUP-patients
      from the Cancer Registry of Norway sampled from 1971 to 2010 are presented, with
      absolute and age-adjusted incidence rates correlated to the total cancer
      incidence. One-year relative survival rates were calculated. RESULTS: The
      incidence of CUP increased both in absolute numbers and as a fraction of total
      cancer incidence during the first half of the period. There has been a
      substantial decrease in incidence over the latest 20 years, now being responsible
      of only 1.7% and 1.2% of the total cancer incidence in females and males,
      respectively, with an age-adjusted incidence rate of 3.5 and 3.8, respectively.
      The one-year relative survival rate has increased and was slightly below 20% for
      both sexes in 2010. CONCLUSION: Better diagnostics, both radiological and
      pathological, is probably responsible for a substantially lower incidence.
      Improved treatment for cancers in general also benefits the CUP-group.

PMID- 23550958
TI  - Whole genome sequencing identifies SCN2A mutation in monozygotic twins with
      Ohtahara syndrome and unique neuropathologic findings.
AB  - Mutations in SCN2A gene cause a variety of epilepsy syndromes. We report a novel
      SCN2A-associated epilepsy phenotype in monozygotic twins with tonic seizures soon
      after birth and a suppression-burst electroencephalography (EEG) pattern. We
      reviewed the medical records, EEG tracings, magnetic resonance imaging (MRI), and
      neuropathologic findings, and performed whole genome sequencing (WGS) on Twin B's
      DNA and Sanger sequencing (SS) on candidate gene mutations. Extensive
      neurometabolic evaluation and early neuroimaging studies were normal. Twin A died
      of an iatrogenic cause at 2 weeks of life. His neuropathologic examination was
      remarkable for dentate-olivary dysplasia and granule cell dispersion of the
      dentate gyrus. Twin B became seizure free at 8 months and was off antiepileptic
      drugs by 2 years. His brain MRI, normal at 2 months, revealed evolving brainstem
      and basal ganglia abnormalities at 8 and 15 months that resolved by 20 months. At
      2.5 years, Twin B demonstrated significant developmental delay. Twin B's WGS
      revealed a heterozygous variant c.788C>T predicted to cause p.Ala263Val change in
      SCN2A and confirmed to be de novo in both twins by SS. In conclusion, we have
      identified a de novo SCN2A mutation as the etiology for Ohtahara syndrome in
      monozygotic twins associated with a unique dentate-olivary dysplasia in the
      deceased twin.

PMID- 23550959
TI  - Profiling the ginsenosides of three ginseng products by LC-Q-TOF/MS.
AB  - Ginseng is a well-known herbal medicine that has been gaining increasingly
      popularity as a potential chemopreventive agent. In traditional Chinese medicine
      practice, white ginseng (WG), red ginseng (RG), and dali ginseng (DG) are 3
      different ginseng-processed products used for different purposes. Although the
      morphological appearance and some constituents contained in these ginseng
      products are similar, their pharmacological activities are significantly
      different due to the varied types and quantity of ginsenosides in each product.
      In the present study, a practical method based on rapid liquid chromatography
      coupled with quadrupole time of flight mass spectrometry (LC-Q-TOF/MS) was
      developed to identify the chemical profiles of ginsenosides in these 3 ginseng
      products. The results demonstrated that a total of 55, 53, and 43 compounds were
      unambiguously assigned or tentatively identified in DG, WG, and RG samples,
      respectively. The featured compounds are mainly malonyl ginsenosides in WG, and
      decarboxyl products of mal-ginsenosides and the dehydrated compounds from polar
      ginsenosides were characteristic in RG, while DG contain some characteristic
      components present both in WG and RG. We presume that heating processing is the
      major factor affecting the chemical profile of ginseng products. The difference
      of chemical information revealed by LC-Q-TOF/MS could be used to discriminate the
      WG, RG, and DG samples.

PMID- 23550960
TI  - 1DTempPro: analyzing temperature profiles for groundwater/surface-water exchange.
AB  - A new computer program, 1DTempPro, is presented for the analysis of vertical one
      dimensional (1D) temperature profiles under saturated flow conditions. 1DTempPro
      is a graphical user interface to the U.S. Geological Survey code Variably
      Saturated 2-Dimensional Heat Transport (VS2DH), which numerically solves the flow
      and heat-transport equations. Pre- and postprocessor features allow the user to
      calibrate VS2DH models to estimate vertical groundwater/surface-water exchange
      and also hydraulic conductivity for cases where hydraulic head is known. 

PMID- 23550961
TI  - Changes in neuroticism following trauma exposure.
AB  - Using longitudinal data, the present study examined change in midlife neuroticism
      following trauma exposure. Our primary analyses included 670 participants (M(age)
      = 60.55; 65.22% male, 99.70% Caucasian) who completed the NEO Personality
      Inventory at ages 42 and 50 and reported their lifetime exposure to traumatic
      events approximately 10 years later. No differences in pre- and post-trauma
      neuroticism scores were found among individuals who experienced all of their
      lifetime traumas in the interval between the personality assessments. Results
      were instead consistent with normative age-related declines in neuroticism
      throughout adulthood. Furthermore, longitudinal changes in neuroticism scores did
      not differ between individuals with and without histories of midlife trauma
      exposure. Examination of change in neuroticism following life-threatening traumas
      yielded a comparable pattern of results. Analysis of facet-level scores largely
      replicated findings from the domain scores. Overall, our findings suggest that
      neuroticism does not reliably change following exposure to traumatic events in
      middle adulthood. Supplemental analyses indicated that individuals exposed to
      life-threatening traumas in childhood or adolescence reported higher midlife
      neuroticism than individuals who experienced severe traumas in adulthood. Life
      threatening traumatic events encountered early in life may have a more pronounced
      impact on adulthood personality than recent traumatic events.

PMID- 23550962
TI  - The association between an abusive father-son relationship, quantity of alcohol
      consumption, and male-to-male alcohol-related aggression.
AB  - BACKGROUND: While alcohol consumption and heavy episodic (binge) drinking are
      well-established predictors of male-to-male alcohol-related aggression (MMARA),
      the role of the father-son relationship in MMARA has yet to be explored. METHODS:
      This study therefore examined whether fathering by the biological father rather
      than another father figure, negative fathering, and gender role modeled by the
      father figure were significant predictors of involvement in MMARA, once drinking
      frequency and quantity and heavy episodic drinking were controlled for. A total
      of 121 university students aged 18 to 25 years (M = 20.63, SD = 1.77 years)
      voluntarily completed the online questionnaire. RESULTS: The only significant
      predictors of perpetration of MMARA were a more abusive paternal relationship and
      drinking quantity (number of standard drinks usually consumed when drinking).
      CONCLUSIONS: Negative father-son relationships may play a role in fostering young
      men's perpetration of MMARA in the barroom context.

PMID- 23550963
TI  - Initiating decision-making in neurology consultations: 'recommending' versus
      'option-listing' and the implications for medical authority.
AB  - This article compares two practices for initiating treatment decision-making,
      evident in audio-recorded consultations between a neurologist and 13 patients in
      two hospital clinics in the UK. We call these 'recommending' and 'option
      listing'. The former entails making a proposal to do something; the latter
      entails the construction of a list of options. Using conversation analysis (CA),
      we illustrate each, showing that the distinction between these two practices
      matters to participants. Our analysis centres on two distinctions between the
      practices: epistemic differences and differences in the slots each creates for
      the patient's response. Considering the implications of our findings for
      understanding medical authority, we argue that option-listing - relative to
      recommending - is a practice whereby clinicians work to relinquish a little of
      their authority. This article contributes, then, to a growing body of CA work
      that offers a more nuanced, tempered account of medical authority than is
      typically portrayed in the sociological literature. We argue that future CA
      studies should map out the range of ways - in addition to recommending - in which
      treatment decision-making is initiated by clinicians. This will allow for further
      evidence-based contributions to debates on the related concepts of patient
      participation, choice, shared decision-making and medical authority. 

PMID- 23550964
TI  - Vascular plants mediate the effects of aridity and soil properties on ammonia
      oxidizing bacteria and archaea.
AB  - An integrated perspective of the most important factors driving the abundance of
      ammonia-oxidizing bacteria (AOB) and archaea (AOA) in natural ecosystems is
      lacking, especially in drylands. We evaluated how different climatic, abiotic,
      and nutrient-related factors determine AOA and AOB abundance in bare and
      vegetated microsites from grasslands throughout the Mediterranean Basin. We found
      a strong negative relationship between the abundance of AOA genes and soil
      fertility (availability of C, N, and P). Aridity and other abiotic factors (pH,
      sand content, and electrical conductivity) were more important than soil
      fertility in modulating the AOA/AOB ratio. AOB were more abundant under vegetated
      microsites, while AOA, highly resistant to stressful conditions, were more
      abundant in bare ground areas. These results suggest that AOA may carry out
      nitrification in less fertile microsites, while AOB predominate under more
      fertile conditions. Our results indicate that the influence of aridity and pH on
      the relative dominance of AOA and AOB genes is ultimately determined by local
      scale environmental changes promoted by perennial vegetation. Thus, in spatially
      heterogeneous ecosystems such as drylands, there is a mutual exclusion and niche
      division between these microorganisms, suggesting that they may be functionally
      complementary. 

PMID- 23550965
TI  - The role of epistasis in the etiology of Polycystic Ovary Syndrome among Indian
      women: SNP-SNP and SNP-environment interactions.
AB  - Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy in women of
      reproductive age. It is a heterogeneous androgen excess disorder determined by
      the interaction of multiple genetic and environmental factors. Our earlier
      analysis on a panel of six candidate genes (Androgen receptor CAG repeats,
      Follistatin, Luteinizing hormone beta subunit, Calpain10, Insulin receptor
      substrate-1 and PPARgamma) based on 250 PCOS cases and 299 controls revealed
      significant association patterns with PCOS among South-Indian women. We report
      here for the first time, the SNP-SNP and SNP-environment interactions of these
      genes in the same cohort. Both multivariate logistic regression as well as
      epistasis analysis (using Multifactor dimensionality reduction software) yielded
      significant results (P < 0.05). All CAPN10 SNPs show association (either risk
      conferring or protective) in the obese group, highlighting the importance of this
      gene in the PCOS pathophysiology. LHP7(LHbeta) and UCSNP44(CAPN10) emerged to be
      the prominent SNPs in the SNP-SNP interaction analysis. The best SNP-SNP
      interaction model was obtained between CAPN10 UCSNP-44 and PPARgamma His447His,
      implying a significant metabolic component in the PCOS pathology. Replicating our
      findings in BMI-specific cohorts in different ethnic populations would be
      warranted in future to identify the physiological networks in PCOS. 

PMID- 23550966
TI  - Cytotoxic, antitopoisomerase IIalpha, and anti-HIV-1 activities of triterpenoids
      isolated from leaves and twigs of Gardenia carinata.
AB  - Eight new cycloartane triterpenoids (1-8), named carinatins A-H, and the known
      compounds secaubryolide (9) and dikamaliartane D (10) were isolated from the
      leaves and twigs of Gardenia carinata. Their structures were determined on the
      basis of spectroscopic methods. Cytotoxic, antitopoisomerase IIalpha, and anti
      HIV-1 activities of compounds 1-7, 9, and 10 were investigated. 

PMID- 23550968
TI  - Review and assessment of poliovirus immunity and transmission: synthesis of
      knowledge gaps and identification of research needs.
AB  - With the intensifying global efforts to eradicate wild polioviruses, policymakers
      face complex decisions related to achieving eradication and managing
      posteradication risks. These decisions and the expanding use of inactivated
      poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity,
      particularly the role of mucosal immunity in the transmission of polioviruses.
      Sustained high population immunity to poliovirus transmission represents a key
      prerequisite to eradication, but poliovirus immunity and transmission remain
      poorly understood despite decades of studies. In April 2010, the U.S. Centers for
      Disease Control and Prevention convened an international group of experts on
      poliovirus immunology and virology to review the literature relevant for modeling
      poliovirus transmission, develop a consensus about related uncertainties, and
      identify research needs. This article synthesizes the quantitative assessments
      and research needs identified during the process. Limitations in the evidence
      from oral poliovirus vaccine (OPV) challenge studies and other relevant data led
      to differences in expert assessments, indicating the need for additional data,
      particularly in several priority areas for research: (1) the ability of IPV
      induced immunity to prevent or reduce excretion and affect transmission, (2) the
      impact of waning immunity on the probability and extent of poliovirus excretion,
      (3) the relationship between the concentration of poliovirus excreted and
      infectiousness to others in different settings, and (4) the relative role of
      fecal-oral versus oropharyngeal transmission. This assessment of current
      knowledge supports the immediate conduct of additional studies to address the
      gaps.

PMID- 23550969
TI  - Developmental changes in executive functioning.
AB  - Although early studies of executive functioning in children supported Miyake et
      al.'s (2000) three-factor model, more recent findings supported a variety of
      undifferentiated or two-factor structures. Using a cohort-sequential design, this
      study examined whether there were age-related differences in the structure of
      executive functioning among 6- to 15-year-olds (N = 688). Children were tested
      annually on tasks designed to measure updating and working memory, inhibition,
      and switch efficiency. There was substantial task-based variation in
      developmental patterns on the various tasks. Confirmatory factor analyses and
      tests for longitudinal factorial invariance showed that data from the 5- to 13
      year-olds conformed to a two-factor structure. For the 15-year-olds, a well
      separated three-factor structure was found.

PMID- 23550970
TI  - Epidemiology of soybean vein necrosis-associated virus.
AB  - Soybean vein necrosis-associated virus has been linked to an emerging soybean
      disease in the United States and Canada. Virus distribution and population
      structure in major growing areas were evaluated. Data were employed to design and
      develop sensitive detection protocols, able to detect all virus isolates
      available in databases. The host range for the virus was assessed and several
      species were found to sustain virus replication, including ivyleaf morning glory,
      a common weed species in soybean-growing areas in the United States. Koch's
      postulates were fulfilled using soybean thrips and transmission efficiency was
      determined. This article provides significant insight into the biology of the
      most widespread soybean virus in the United States.

PMID- 23550971
TI  - Genetically diverse long-lived clonal lineages of Phytophthora capsici from
      pepper in Gansu, China.
AB  - Phytophthora capsici causes significant loss to pepper production in China, and
      our objective was to investigate the population structure in Gansu province.
      Between 2007 and 2011, 279 isolates were collected from pepper at 24 locations.
      Isolates (or subsets) were assessed for simple sequence repeat (SSR) genotype,
      metalaxyl resistance, mating type, and physiological race using cultivars from
      the World Vegetable Center (AVRDC) and New Mexico recombinant inbred lines
      (NMRILs). The A1 and A2 mating types were recovered from nine locations and
      metalaxyl-resistant isolates from three locations. A total of 104 isolates tested
      on the AVRDC panel resolved five physiological races. None of 42 isolates tested
      on the NMRIL panel caused visible infection. SSR genotyping of 127 isolates
      revealed 59 unique genotypes, with 42 present as singletons and 17 having 2 to 13
      isolates. Isolates with identical genotypes were recovered from multiple sites
      across multiple years and, in many cases, had different race types or metalaxyl
      sensitivities. Isolates clustered into three groups with each group having almost
      exclusively the A1 or A2 mating type. Overall it appears long-lived genetically
      diverse clonal lineages are dispersed across Gansu, outcrossing is rare, and
      functionally important variation exists within a clonal framework.

PMID- 23550972
TI  - Selection pressure and founder effects constrain genetic variation in
      differentiated populations of soilborne bymovirus Wheat yellow mosaic virus
      (Potyviridae) in China.
AB  - To study the population genetic structure and forces driving the evolution of
      Wheat yellow mosaic virus (WYMV), the nucleotide sequences encoding the coat
      protein (CP) (297 sequences) or the genome-linked virion protein (VPg) (87
      sequences) were determined from wheat plants growing at 11 different locations
      distributed in five provinces in China. There were close phylogenetic
      relationships between all sequences but clustering on the phylogenetic trees was
      congruent with their provenance, suggesting an origin-dependent population
      genetic structure. There were low levels of genetic diversity, ranging from
      0.00035 +/- 0.00019 to 0.01536 +/- 0.00043 (CP), and 0.00086 +/- 0.00039 to
      0.00573 +/- 0.00111 (VPg), indicating genetic stability or recent emergence of
      WYMV in China. The results may suggest that founder effects play a role in
      shaping the genetic structure of WYMV. Between-population diversity was
      consistently higher than within-population diversity, suggesting limited gene
      flow between subpopulations (average FST 0.6241 for the CP and 0.7981 for the
      VPg). Consistent amino acid substitutions correlated with the provenance of the
      sequences were observed at nine positions in the CP (but none in the VPg),
      indicating an advanced stage in population structuring. Strong negative
      (purifying) selection was implicated on both the CP and VPg but positive
      selection on a few codons in the CP, indicating an ongoing molecular adaptation.

PMID- 23550973
TI  - Genetic transformation of the obligate parasite Plasmodiophora brassicae.
AB  - A protocol for genetic transformation of the obligate parasite Plasmodiophora
      brassicae, causal agent of clubroot of crucifers, was developed. In this
      protocol, protoplast preparation was superseded with lithium acetate treatment
      and the selection step was omitted. In two independent experiments, germinating
      resting spores of P. brassicae were transformed by two fungal expression vectors
      containing either a green fluorescent protein (gfp) gene or a hygromycin
      resistance (hph) gene. Putative transformants were produced from both
      transformations, with ~50% of the obtained galls containing resting spores from
      which transforming DNA could be detected by polymerase chain reaction (PCR). PCR,
      quantitative PCR (qPCR), and genome walking conducted on selected transformants
      indicated that the transforming DNA was intergraded into the P. brassicae genome.
      Transcript of hph but not gfp was detected by reverse-transcription qPCR from
      selected transformants. From all galls produced by transformants, no GFP activity
      could be identified. Verified transformants were inoculated on canola and new
      galls were generated. PCR and qPCR analyses based on these galls indicated that
      transforming DNA was still resident in P. brassicae. This is the first report on
      genetic transformation of P. brassicae. The information and data generated from
      this study will facilitate research in multiple areas of the clubroot
      pathosystem.

PMID- 23550974
TI  - Functional analysis of the promoter of a glycosyl hydrolase gene induced in
      resistant Sinapis alba by Alternaria brassicicola.
AB  - A putative family 3 glycosyl hydrolase (GH) gene showed significant differential
      expression in resistant Sinapis alba, compared with the susceptible Brassica
      juncea, as part of the initial responses during interaction with the necrotroph
      Alternaria brassicicola. To understand the mechanism of induction, the promoter
      was isolated and deletion analysis carried out. All the promoter fragments were
      fused with the beta-glucuronidase gene and the expressions were studied in stable
      B. juncea transgenics and transiently transformed Nicotiana tabacum. Analysis of
      the expression of the promoter showed the presence of functional abscisic acid
      (ABA)-, jasmonic acid (JA)-, and salicylic acid (SA)-responsive cis elements.
      Interestingly, the promoter was found to be induced in both S. alba and B. juncea
      upon challenge with A. brassicicola but, in S. alba, SA had an inhibitory effect
      on the pathogen-induced expression of the gene whereas, in B. juncea, SA did not
      have any negative effect. Therefore, the SA-mediated inhibition in S. alba
      indicates that the induction is probably through JA or ABA signaling. The
      difference in the mechanism of induction of the same promoter in the resistant
      and susceptible plants is probably due to the differential hormonal responses
      initiated upon challenge with A. brassicicola.

PMID- 23550975
TI  - Response to Comment on "Atmospheric degradation of perfluoro-2-methyl-3
      pentanone: photolysis, hydrolysis, and hydration".

PMID- 23550977
TI  - Effects of reclining posture on velopharyngeal closing pressure during swallowing
      and phonation.
AB  - Velopharyngeal closure plays an important role in preventing air pressure leakage
      during swallowing and phonation from oropharynx to nasopharynx. Levator veli
      palatini muscle activity is influenced by oral and nasal air pressure, volume of
      the swallow bolus and postural changes. However, it is unclear how velopharyngeal
      closing pressure is affected by reclining posture. The purpose of this study was
      to investigate the effects of reclining posture on velopharyngeal closing
      pressure during swallowing and phonation. Nine healthy male volunteers (age
      range, 27-34 years) participated in this study. Velopharyngeal closing pressure
      during a dry swallow, a 5-mL liquid swallow, a 5-mL honey-thick liquid swallow
      and phonations of /P?/ and /K?/ were evaluated in an upright posture and at
      reclining postures of 60 degrees  and 30 degrees . A manometer catheter was
      inserted transnasally onto the soft palate, and each trial was repeated three
      times. A solid-state manometer catheter with an intra-luminal transducer was used
      to evaluate the amplitude and duration of each trial, and data were statistically
      analysed. Average amplitudes during dry and liquid swallows were significantly
      lower in reclining postures compared with the upright posture, but the amplitude
      was not significantly different during the thick liquid swallow. Average
      durations were not affected by postural changes. The amplitudes during phonations
      were lower in reclining postures, but the differences were not significant.
      Velopharyngeal closure is significantly affected by reclining posture. This
      suggests that velopharyngeal closing pressure may be adjusted according to
      afferent inputs, such as reclining posture and bolus viscosity.

PMID- 23550976
TI  - Lipodystrophy and inflammation predict later grip strength in HIV-infected men:
      the MACS Body Composition substudy.
AB  - Body fat changes in HIV-infected persons are associated with increased systemic
      inflammation and increased mortality. It is unknown whether lipodystrophy is also
      associated with declines in physical function. Between 2001 and 2003, 33 HIV
      infected men with evidence of lipodystrophy (LIPO+), 23 HIV-infected men without
      lipodystrophy (LIPO-), and 33 seronegative men were recruited from the
      Multicenter AIDS Cohort Study (MACS) for the Body Composition substudy. Visceral
      adipose tissue (VAT) was assessed by quantitative computed tomography. Lean body
      mass (LBM) and extremity fat were measured by dual-energy x-ray absorptiometry.
      Insulin resistance was estimated by Homeostatic Model Assessment (HOMA). Serum
      interleukin (IL)-6, soluble tumor necrosis factor (TNF)-alpha receptors I and II
      (sTNFRI and sTNFRII), and highly sensitive C-reactive protein (hs-CRP)
      concentrations were quantified from archived serum samples. These measurements
      were correlated with grip strength measured in 2007 using linear regression. At
      the substudy visit, the LIPO+ group had higher HOMA, sTNFRI, sTNFRII, and IL-6
      levels than the LIPO- group. In 2007, the LIPO+ group had lower median grip
      strength than the LIPO- group (34.4 vs. 42.7 kg, p=0.002). Multivariable analysis
      of HIV+ men showed older age, lower LBM, higher sTNFRII concentrations, and LIPO+
      status [adjusted mean difference -4.9 kg (p=0.045)] at the substudy visit were
      independently associated with lower subsequent grip strength. Inflammation, lower
      LBM, and lipodystrophy in HIV-infected men were associated with lower subsequent
      grip strength. These findings suggest that inflammation may contribute to
      declines in functional performance, independent of age.

PMID- 23550978
TI  - Photoinactivation of bacteria attached to glass and acrylic surfaces by 405 nm
      light: potential application for biofilm decontamination.
AB  - Attachment of bacteria to surfaces and subsequent biofilm formation remains a
      major cause of cross-contamination capable of inducing both food-related illness
      and nosocomial infections. Resistance to many current disinfection technologies
      means facilitating their removal is often difficult. The aim of this study was to
      investigate the efficacy of 405 nm light for inactivation of bacterial attached
      as biofilms to glass and acrylic. Escherichia coli biofilms (10(3)-10(8) CFU mL(
      1)) were generated on glass and acrylic surfaces and exposed for increasing times
      to 405 nm light (5-60 min) at ca 140 mW cm(-2). Successful inactivation of
      biofilms has been demonstrated, with results highlighting complete/near-complete
      inactivation (up to 5 log10 reduction on acrylic and 7 log10 on glass). Results
      also highlight that inactivation of bacterial biofilms could be achieved whether
      the biofilm was on the upper "directly exposed" surface or "indirectly exposed"
      underside surface. Statistically significant inactivation was also shown with a
      range of other microorganisms associated with biofilm formation (Staphylococcus
      aureus, Pseudomonas aeruginosa and Listeria monocytogenes). Results from this
      study have demonstrated significant inactivation of bacteria ranging from
      monolayers to densely populated biofilms using 405 nm light, highlighting that
      with further development this technology may have potential applications for
      biofilm decontamination in food and clinical settings.

PMID- 23550979
TI  - Physical characterization and recovery of corroded fingerprint impressions from
      postblast copper pipe bomb fragments.
AB  - Pipe bombs made from 1 mm thick copper pipe were detonated with a low explosive
      power powder. Analysis of the physical characteristics of fragments revealed that
      the copper had undergone work hardening with an increased Vickers Hardness of
      107HV1 compared with 80HV1 for unexploded copper pipe. Mean plastic strain prior
      to fracture was calculated at 0.28 showing evidence of both plastic deformation
      and wall thinning. An examination of the external surface showed microfractures
      running parallel with the length of the pipe at approximately 100 MUm intervals
      and 1-2 MUm in width. Many larger fragments had folded "inside out" making the
      original outside surface inaccessible and difficult to fold back through work
      hardening. A visual examination for fingerprint corrosion revealed ridge details
      on several fragments that were enhanced by selective digital mapping of colors
      reflected from the surface of the copper. One of these fingerprints was
      identified partially to the original donor.

PMID- 23550980
TI  - EHRs, EMRs, and health information technology: to meaningful use and beyond: a
      symposium introduction and overview.

PMID- 23550981
TI  - Meaningful adoption: what we know or think we know about the financing,
      effectiveness, quality, and safety of electronic medical records.

PMID- 23550982
TI  - Meaningful EHR attributes for an era of accountability, transparency, shared
      decision making, and value assessment.

PMID- 23550983
TI  - Interoperable electronic health care record: a case for adoption of a national
      standard to stem the ongoing health care crisis.

PMID- 23550984
TI  - Leveling the playing field: the call to require states to make and follow minimum
      national standards for licensing mixed martial artists that use testosterone
      replacement therapy.

PMID- 23550985
TI  - My kid, the future olympian: predictive and genetic aptitude testing and the case
      for regulation.

PMID- 23550988
TI  - Methylenetetrahydrofolate reductase C677T and overall survival in pediatric acute
      lymphoblastic leukemia: a systematic review.
AB  - A summary of the evidence pertaining to the association between
      methylenetetrahydrofolate reductase (MTHFR) C677T and overall survival in
      pediatric acute lymphoblastic leukemia (ALL) is not currently available. We thus
      reviewed the literature on the association between MTFHR C677T and overall
      survival in pediatric ALL. We searched PubMed/MEDLINE, Scopus and ISI Web of
      Knowledge literature databases without language restrictions to identify
      observational studies among children diagnosed between ages 0 and 19 years that
      assessed MTHFR 677 polymorphisms in relation to ALL survival. We identified six
      studies comprising 909 pediatric patients with ALL. The magnitude of relative
      risk (RR) for pediatric ALL mortality varied by genotype comparison and study
      population, ranging from RR = 0.84 (95% confidence limits [CL]: 0.24, 3.0) for a
      TT vs. CT/CC comparison to RR = 7.0 (95% CL: 0.98, 49) for a TT vs. CC
      comparison. The current evidence suggests that individuals with MTHFR 677
      variants (i.e. at least one T allele) may have a higher relative risk of
      pediatric ALL mortality, with greater statistical support for MTHFR 677TT. With
      more detailed supporting evidence, MTHFR 677 genotyping at diagnosis could
      provide an option for individualizing therapy and further reducing pediatric ALL
      mortality in certain populations.

PMID- 23550989
TI  - Natural killer cell receptor repertoire is comparable amongst newly diagnosed
      acute myeloid leukemia of different French-American-British subtypes, risk
      categories and chemosensitivities.
AB  - We studied the natural killer (NK) receptor repertoire by flow cytometry for 78
      patients with newly diagnosed acute myeloid leukemia (AML) and correlated the
      expression with their biological and clinical characteristics. CD3-CD56+ NK cells
      constituted a median of 11.68% of the lymphocyte subset. The NK receptors
      including the killer immunoglobulin-like receptors, natural cytotoxicity
      receptors and C-type lectin receptors were comparable amongst the various French
      American-British (FAB) subtypes and amongst patients in the better, intermediate
      and poor risk categories. Neither was there any difference in NK receptor
      repertoire between patients who achieved a remission with induction chemotherapy
      and those who were chemorefractory, indicating the absence of a prognostic impact
      of NK receptor repertoire at the time of diagnosis of AML. Compared with NK cells
      from 16 healthy donors, most of the NK receptors were expressed at a
      significantly lower level, suggesting a defective NK cell population as a cause
      or result of AML.

PMID- 23550990
TI  - Analysis of WT1 mutations, expression levels and single nucleotide polymorphism
      rs16754 in de novo non-M3 acute myeloid leukemia.
AB  - The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been
      described as a possible prognostic marker in patients with acute myeloid leukemia
      (AML). However, the results in this field are not reproducible in different
      cohorts. In this study, we investigated WT1 mutations, expression levels and SNP
      rs16754 in a cohort of 122 adult patients with AML. As the major allele (65.6%)
      in a Chinese population, WT1(GG) was associated with younger age (<= 60) and
      lower percentage of blasts than WT1(GA/AA). Meanwhile, improved overall survival
      (OS, p = 0.035) and disease-free survival (DFS, p = 0.021) were observed in
      WT1(GG) compared with WT1(GA/AA). We then found that WT1 mutation, occurring in
      8% of patients with AML, did not predict clinical outcome. Finally, WT1 levels
      were higher in patients with WT1(GG) than in those with WT1(GA/AA). However, high
      levels of WT1 (> median) predicted worse OS (p = 0.015) and DFS (p = 0.034) than
      low levels of WT1 (<= median). However, further studies are required to elucidate
      the mechanism of why WT1(GG), which was associated with higher median expression
      of WT1 that predicts worse OS and DFS compared to low expression of WT1,
      predicted better OS and DFS compared with WT1(GA/AA). In summary, WT1 rs16754 and
      WT1 expression have a significant impact on clinical outcome in patients with
      AML.

PMID- 23550991
TI  - Early lymphocyte recovery predicts superior overall survival after unmanipulated
      haploidentical blood and marrow transplant for myelodysplastic syndrome and acute
      myeloid leukemia evolving from myelodysplastic syndrome.
AB  - We investigated whether early lymphocyte recovery, after unmanipulated,
      haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in
      78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia
      evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count
      on day 30 (ALC-30). Patients with high ALC-30 (>= 300 cells/MUL) had lower
      relapse rates (13.8% vs. 35.5%, p = 0.049) and lower incidence of bacterial
      infections (3.4% vs. 25.8%, p = 0.015) than those with low ALC-30 values.
      Multivariate analysis showed that a high ALC-30 was associated with improved
      overall survival (OS, hazard ratio [HR]: 0.099, 95% confidence interval [CI]:
      0.029-0.337; p < 0.0001), improved leukemia-free survival (HR: 0.245, 95% CI:
      0.112-0.539; p < 0.0001), lower relapse rate (HR: 0.096, 95% CI: 0.011-0.827; p =
      0.033) and lower transplant-related mortality (TRM, HR: 0.073, 95% CI: 0.016
      0.324; p = 0.001). Combinations of three mismatches in the human leukocyte
      antigen loci were associated with a higher TRM (HR: 5.026, 95% CI: 1.392-18.173;
      p = 0.014). Our results suggest that the ALC-30 can predict a favorable OS after
      unmanipulated HBMT.

PMID- 23550992
TI  - Arsenic: an old enemy now turned friend.

PMID- 23550993
TI  - Molecular lesions in B-cell lymphoproliferative disorders: recent contributions
      from studies utilizing high-throughput sequencing techniques.
AB  - Next-generation sequencing techniques are powerful high-throughput methods that
      have enabled the comprehensive documentation of genetic lesions in numerous
      hematological malignancies. In recent times, the genomes of multiple different B
      cell lymphoproliferative disorders including chronic lymphocytic leukemia,
      diffuse large B-cell lymphoma, Burkitt lymphoma, splenic marginal zone lymphoma,
      mantle cell lymphoma, hairy cell leukemia and Waldenstrom macroglobulinemia have
      been documented. Between them, these studies have reinforced and provided insight
      into the mechanisms for the dysregulation of known pathways (e.g. nuclear factor
      kappaB [NF-kappaB]), uncovered the importance of new pathways for oncogenesis
      (e.g. mRNA processing), identified disease-defining mutations and provided
      meaningful new targets which are already being translated into therapeutic
      interventions. This review summarizes the molecular lesions that have been
      discovered in B-cell lymphoproliferative disorders thus far by studies utilizing
      high-throughput sequencing techniques and the aberrations in the numerous
      intracellular pathways that have been shown to be involved.

PMID- 23550994
TI  - Network meta-analysis of the outcome 'participant complete clearance' in
      nonimmunosuppressed participants of eight interventions for actinic keratosis: a
      follow-up on a Cochrane review.
AB  - The conclusions of pairwise meta-analyses of interventions for actinic keratosis
      (AK) are limited due to the lack of direct comparison between some interventions.
      Consequently, we performed a network meta-analysis for eight treatments [5
      aminolaevulinic acid (ALA)-photodynamic therapy (PDT), cryotherapy, diclofenac 3%
      in 2.5% hyaluronic acid (DCF/HA), 5-fluorouracil (5-FU) 0.5% or 5.0%, imiquimod
      (IMI) 5%, ingenol mebutate (IMB) 0.015-0.05%, methyl aminolaevulinate (MAL)-PDT
      and placebo/vehicle (including placebo-PDT)] to determine their relative
      efficacies. As part of a prior Cochrane systematic review, different databases
      and grey literature were searched for randomized controlled trials up to April
      2012. The inclusion criteria were parallel-group studies with nonimmunosuppressed
      participants: (i) reporting 'participant complete clearance' and (ii) comparing
      at least two of the interventions. Thirty-two publications met the criteria and
      they included the following number of individual or pooled studies (n) and total
      number of participants (N) for the different interventions: 5-FU 0.5% (n = 4, N =
      169), 5-FU 5.0% (n = 2, N = 44), ALA-PDT (n = 6, N = 739), cryotherapy (n = 2, N
      = 174), DCF/HA (n = 5, N = 299), IMI (n = 14, N = 1411), IMB (n = 3, N = 560),
      MAL-PDT (n = 7, N = 557) and placebo (n = 32, N = 2520). Network analyses using a
      random-effects Bayesian model were carried out with the software ADDIS v1.16.1.
      The interventions were ranked as follows based on calculated probabilities and
      odd ratios: 5-FU > ALA-PDT ~ IMI ~ IMB ~ MAL-PDT > cryotherapy > DCF/HA >
      placebo. This efficacy ranking was obtained based on the current available data
      on 'participant complete clearance' from randomized controlled trials and the
      analysis model used. However, several other factors should also be considered
      when prescribing a treatment for AK.

PMID- 23550995
TI  - Bias of apparent tracer ages in heterogeneous environments.
AB  - The interpretation of apparent ages often assumes that a water sample is composed
      of a single age. In heterogeneous aquifers, apparent ages estimated with
      environmental tracer methods do not reflect mean water ages because of the mixing
      of waters from many flow paths with different ages. This is due to nonlinear
      variations in atmospheric concentrations of the tracer with time resulting in
      biases of mixed concentrations used to determine apparent ages. The bias of these
      methods is rarely reported and has not been systematically evaluated in
      heterogeneous settings. We simulate residence time distributions (RTDs) and
      environmental tracers CFCs, SF6 , (85) Kr, and (39) Ar in synthetic heterogeneous
      confined aquifers and compare apparent ages to mean ages. Heterogeneity was
      simulated as both K-field variance (sigma(2) ) and structure. We demonstrate that
      an increase in heterogeneity (increase in sigma(2) or structure) results in an
      increase in the width of the RTD. In low heterogeneity cases, widths were
      generally on the order of 10 years and biases generally less than 10%. In high
      heterogeneity cases, widths can reach 100 s of years and biases can reach up to
      100%. In cases where the temporal variations of atmospheric concentration of
      individual tracers vary, different patterns of bias are observed for the same
      mean age. We show that CFC-12 and CFC-113 ages may be used to correct for the
      mean age if analytical errors are small. 

PMID- 23550996
TI  - Comments and reflections on ethics in screening for biomarkers of prenatal
      alcohol exposure.
AB  - Early identification of and intervention for fetal alcohol spectrum disorder
      (FASD) has been shown to optimize outcomes for affected individuals. Detecting
      biomarkers of prenatal alcohol exposure (PAE) in neonates may assist in the
      identification of children at risk of FASD enabling targeted early interventions.
      Despite these potential benefits, complicated ethical issues arise in screening
      for biomarkers of PAE and these must be addressed prior to the implementation of
      screening programs. Here, we identify and comment, based on a North American
      perspective, on concerns raised in the current ethical, social, and legal
      literature related to meconium screening for PAE. Major ethical concerns revolve
      around the targeting of populations for PAE screening, consent and respect for
      persons, stigma and participation rates, the cost-benefit analysis of a screening
      program, consequences of false-positive and false-negative test results,
      confidentiality and appropriate follow-up to positive screen results, and the use
      of screen results for criminal prosecution. We identify gaps in the literature on
      screening for PAE, most notably related to a lack of stakeholder perspectives
      (e.g., parents, healthcare providers) about screening and the ethical challenges
      it presents. 

PMID- 23550997
TI  - A cross-sectional study of the association between circulating TSH level and
      lipid profile in a large Spanish population.
AB  - OBJECTIVE: Some evidence suggests that high serum TSH levels are associated with
      an adverse lipid profile, but this association is not clear when plasma TSH is
      within the reference range. Nevertheless, these studies have never been conducted
      in Spain, a country with a strong adherence to the Mediterranean diet. The study
      aim was to analyse the association between blood TSH levels and circulating
      lipids in a large Spanish population and set up a TSH reference range in
      different age, gender and Body Mass Index (BMI) subpopulations from our cohort.
      DESIGN: Cross-sectional study on 20 783 subjects. PATIENTS: We analysed
      circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol
      (LDLc), high-density lipoprotein cholesterol (HDLc) and triglycerides (TG) and
      compared them with TSH serum levels. Discriminant function analysis was used to
      determine the TSH cut-off level from where hyperlipidaemia developed. RESULTS: In
      individuals free of thyroid dysfunction, the mean and the 95% TSH (mU/l)
      reference limits were 2.20 and 0.72-4.43, respectively. We observed a sex-related
      difference in TSH concentration (men, 2.07 and 0.72-4.29; women, 2.29 and 0.72
      4.49; P < 0.01). We also observed a weight-related difference in TSH
      concentration (BMI < 30 kg/m(2) , 2.16 and 0.72-4.39; BMI >= 30 kg/m(2) , 2.28
      and 0.71-4.47; P < 0.01). TSH was positively associated with TC, TG and LDLc
      levels and negatively with HDLc. CONCLUSION: We found an association between TSH
      and lipids in that as TSH increased, the lipid profile became less favourable,
      even within the normal range. Additionally, TSH reference ranges varied according
      to gender, age and BMI.

PMID- 23550998
TI  - Potential of sawdust as a green and economical sorbent for simultaneous
      preconcentration of trace amounts of cadmium, cobalt, and lead from water,
      biological, food, and herbal samples.
AB  - Application of treated sawdust with NaOH as a green and economical sorbent for
      simultaneous preconcentration of trace amounts of Cd(II), Co(II), and Pb(II) ions
      from liver, lettuce, fish, and water as test samples with complicated matrices
      was investigated. Various parameters, such as effect of pH and contact time,
      breakthrough volume, type, and concentration of eluent and interference of ions
      were studied. The sorption was quantitative in the pH of 5.0 to 7.0 and
      desorption occurred instantaneously with 5.0 mL of mixed solutions of ethanol and
      2.0 mol/L HNO3 -HCl and the amount of ions was measured by using flame atomic
      absorption spectrometry. Linearity was maintained at 3 to 500 MUg/L for cobalt,
      5.0 to 800 MUg/L for lead, and 2.0 to 300 MUg/L for cadmium in the original
      solution. The relative standard deviation was less than 1.80% (n = 6, with
      concentration of 0.3 mg/L for cadmium and 0.5 mg/L for lead and cobalt).
      Detection limits and maximum capacity of the sorbent for Co (II), Cd (II), and Pb
      (II) in the original solution were 0.86, 0.50, and 1.7 MUg/L and 28.5, 30.6, and
      47.3 mg/g, respectively. The results for spiked real samples, effect of
      interfering ions, and adsorption capacity indicated that the applicability of
      this method for lead preconcentration is better than cadmium and cobalt
      preconcentration from complicated matrices. Practical Application: Sawdust can be
      applied as a green and economical sorbent for simultaneous preconcentration and
      solid-phase extraction of metal ions from food and environmental samples with
      complicated matrices.

PMID- 23550999
TI  - Acquiring and maintaining professional excellence.

PMID- 23551000
TI  - Knowledge, skills and professional behaviours required by occupational therapist
      and physiotherapist beginning practitioners in work-related practice: a
      systematic review.
AB  - BACKGROUND/AIM: Occupational therapists and physiotherapists have established
      roles in work-related practice. However, there is limited information about the
      attributes required by these professions for competent practice in this field.
      The aim of this systematic review was to evaluate the research literature to
      determine the knowledge, skills and professional behaviours required by
      occupational therapists and physiotherapists, including new graduates, in work
      related practice. METHODS: A systematic search was conducted of standard
      databases using keywords and phrases. All types of studies and reports were
      included from empirical research to descriptive reports. Included literature was
      appraised by standard critical appraisal tools by two reviewers. Words, phrases
      or themes related to the attributes required for work practice were manually
      extracted and a meta-synthesis conducted. RESULTS: Seven observational studies,
      six professional practice guidelines, one book chapter, one journal editorial and
      seven opinion pieces met the inclusion criteria. Observational studies and
      descriptive reports were low on the evidence hierarchy. Meta-synthesis determined
      that key attributes required by occupational therapists and physiotherapists in
      work-related practice were knowledge of injury prevention and management, skills
      in communication, and professional behaviours of self-reflection and evaluation.
      CONCLUSION: Findings from this systematic review provided credible evidence about
      attributes required by occupational therapists and physiotherapists but not
      including new graduates, in work-related practice. However, due to low evidence
      levels findings will need to be applied with caution. More rigorous research is
      needed to evaluate occupational therapy and physiotherapy workplace interventions
      to guide practice and to assist occupational therapists and physiotherapists
      promote the effectiveness of their services.

PMID- 23551001
TI  - Work outcomes and their predictors in the Redesigning Daily Occupations (ReDO)
      rehabilitation programme for women with stress-related disorders.
AB  - BACKGROUND/AIM: Previous research has shown that the Redesigning Daily
      Occupations programme reduced the degree of sick leave and increased return to
      work rates among women on sick leave for stress-related disorders when compared
      with "care as usual". To further investigate the Redesigning Daily Occupations
      intervention, this study explored changes in the work situation from baseline to
      a 12-month follow-up in the Redesigning Daily Occupations group compared with the
      "care as usual" group and analysed any predictors of change. METHODS: A matched
      control design was used and 84 women were recruited. Objective (return to work
      and sick leave) and subjective work outcomes (perceptions of the worker role and
      the work environment) were explored. Potential predictors were clinical and
      demographic variables and an anxiety-depression factor. RESULTS: In both groups,
      large positive effect sizes from baseline to follow-up were found regarding the
      objective outcomes, a moderate positive effect size was found for perceived work
      environment, whereas perceived worker role remained unaffected. Previous work
      rehabilitation predicted objective work outcomes in both groups. Higher education
      and older age were predictors of subjective outcomes in the Redesigning Daily
      Occupations group, whereas a more severe anxiety-depression rating was negative
      for work environment ratings in the "care as usual" group. CONCLUSIONS: Return to
      work seemed possible without a change in the women's perceptions of the worker
      role; rather they renegotiated their view of the work environment. The
      Redesigning Daily Occupations programme was found to be promising, with a
      positive effect on return to work and sick leave reduction. It seemed more
      suitable for the higher educated and older women.

PMID- 23551002
TI  - Preferences for rehabilitation service delivery: a comparison of the views of
      patients, occupational therapists and other rehabilitation clinicians using a
      discrete choice experiment.
AB  - BACKGROUND/AIM: Understanding the differences in preferences of patients and
      occupational therapists for the way in which rehabilitation services are provided
      is important. In particular, it is unknown whether new approaches to
      rehabilitation such as high intensity therapy and virtual reality programs are
      more or less acceptable than traditional approaches. METHODS: A discrete choice
      experiment was conducted to assess and compare the acceptability of these new
      approaches, relative to other characteristics of the rehabilitation program. The
      study included patients participating in a stroke or medical rehabilitation
      program (n = 100), occupational therapists (n = 23) and other clinicians (n = 91)
      working in rehabilitation settings at three hospitals in South Australia. Data
      were analysed using a conditional (fixed-effects) logistic regression model.
      RESULTS: The model coefficient attached to very high intensity therapy programs
      (defined as six hours per day) was negative and highly statistically significant
      for both patients and therapists indicating aversion for this option. In
      addition, other rehabilitation clinicians and patients were strongly averse to
      the use of virtual reality programs (as evidenced by the negative and highly
      statistically significant coefficient attached to this attribute for both groups)
      relative to occupational therapists. CONCLUSION: The comparison of the views of
      patients, occupational therapists and other rehabilitation clinicians revealed
      some differences. All participants (patients and clinicians) showed an
      inclination for programs that resulted in the best recovery. However, patients
      expressed stronger preferences than clinicians for traditional therapy
      approaches. As a group, occupational therapists were most likely to accept
      approaches such as virtual reality suggesting changes away from traditional
      delivery methods will be more readily integrated into practice.

PMID- 23551003
TI  - Understanding the dimensions of home that impact on home modification decision
      making.
AB  - BACKGROUND/AIM: The home environment is a multidimensional and personally
      meaningful place, and the complexity of this environment often impacts on the
      home modification process and outcomes. Home modifications can appear as a
      straightforward solution to safety and occupational performance concerns;
      nevertheless, clients sometimes reject modifications or are unsatisfied with the
      completed works. To understand this phenomenon, this study aimed to determine
      what aspects of the home environment impact home modification decision making.
      METHOD: In this qualitative descriptive study, 42 in-depth interviews using a
      semi-structured questionnaire were undertaken and analysed using a template
      analysis. The interviews explored the experience of the home modification
      process, including concerns and the decisions made about the modifications.
      FINDINGS: Four dimensions of the home environment were commonly found to affect
      decision making namely, the personal, societal, physical and temporal dimensions
      of home as well as social and occupational dimensions. CONCLUSIONS: An
      understanding of the dimensions of home that impact decision making provides
      occupational therapists with a greater appreciation of the experience of home and
      allows them to enhance the effectiveness and acceptance of home modifications.

PMID- 23551004
TI  - Factors that influence the professional resilience of occupational therapists in
      mental health practice.
AB  - BACKGROUND/AIM: Mental health practice can create challenging environments for
      occupational therapists. This study explores the dynamic processes involved in
      the development and maintenance of professional resilience of experienced mental
      health occupational therapy practitioners. It presents the PRIOrity model that
      summarises the dynamic relationship between professional resilience, professional
      identity and occupation-based practice. METHODS: A narrative inquiry methodology
      with two phases of interviews was used to collect the data from nine experienced
      mental health practitioners. Narrative thematic analysis was used to interpret
      the data. RESULTS: Professional resilience was linked to: (i) professional
      identity which tended to be negatively influenced in contexts dominated by
      biomedical models and psychological theories; (ii) expectations on occupational
      therapists to work outside their professional domains and use generic knowledge;
      and (iii) lack of validation of occupation-focussed practice. Professional
      resilience was sustained by strategies that maintained participants' professional
      identity. These strategies included seeking 'good' supervision, establishing
      support networks and finding a job that allowed a match between valued knowledge
      and opportunities to use it in practice. CONCLUSION: For occupational therapists
      professional resilience is sustained and enhanced by a strong professional
      identity and valuing an occupational perspective of health. Strategies that
      encourage reflection on the theoretical knowledge underpinning practice can
      sustain resilience. These include supervision, in-service meetings and informal
      socialisation. Further research is required into the role discipline-specific
      theories play in sustaining professional values and identity. The development of
      strategies to enhance occupational therapists' professional resilience may assist
      in the retention of occupational therapists in the mental health workforce.

PMID- 23551005
TI  - New Zealand occupational therapists' views on evidence-based practice: a
      replicated survey of attitudes, confidence and behaviours.
AB  - BACKGROUND/AIM: Evidence-based practice is internationally recognised as an
      essential component of contemporary occupational therapy, and as being critical
      to the future of the profession. However, its uptake by therapists has been
      modest with barriers such as therapists attitudes, skills and organisational
      support frequently cited. This study explored New Zealand therapists' perceptions
      of their behaviours, skills and attitudes regarding evidence-based practice.
      METHOD: A survey comprising open and closed questions was emailed to all
      therapists holding practicing certificates who had consented to be contacted
      about research (n = 1587) with 30% (n = 473) of surveys returned. Therapists'
      evidence-based practice attitudes, skills and behaviours were examined using
      descriptive statistics. Relationships between therapists' perceptions of evidence
      based practice and demographic characteristics of therapists were explored using
      Chi-square analysis. Text responses were analysed using content analysis.
      RESULTS: New Zealand therapists have a positive attitude towards evidence-based
      practice (84%), but report moderate reference to research literature (56%) during
      clinical decision-making and moderate (66%) to low (35%) levels of confidence in
      research-related skills. Therapists with training in evidence-based practice had
      higher levels of confidence, perceived research as more relevant to practice and
      reported less barriers to implementing evidence-based practice than other
      therapists. A perception that evidence-based practice is separate to clinical
      reasoning was widely held. CONCLUSION: New Zealand therapists' evidence-based
      practice behaviours, skills and attitudes are largely consistent with
      international comparisons. However, if New Zealand therapists are to enact the
      ideal of being 'evidence-based' then accessible training in evidence-based
      practice-related skills is indicated and should include education of what
      evidence-based practice means.

PMID- 23551006
TI  - Exploring the mobility preferences and perceived difficulties in using transport
      and driving with a sample of healthy and outpatient older adults in Singapore.
AB  - BACKGROUND/AIM: While activity engagement is important to older adults,
      limitations in ability can affect transport mode choice and subsequent activity
      participation. Therefore, this study aimed to explore the mobility preferences
      and difficulties in using public transport and driving with a sample of older
      adults in Singapore, with specific reference to accessing everyday activities.
      METHODS: One hundred and sixty-two persons aged 50 years and over were recruited
      through a community event, and an outpatient occupational therapy department.
      They self-completed structured questionnaire forms which were analysed using
      parametric and non-parametric statistics, including t-tests and ANOVAs. RESULTS:
      The majority of the participants were in the paid workforce and no significant
      differences were found between gender and the importance of transport for access
      to various activities, but a significant association was found for age and use of
      transport for going to work, F(5,101) = 3.07, P = 0.01. The majority of the
      drivers drove at least once a day, and 19% of them reported having noticed
      declines in their driving capabilities in the past four years, and indicated
      driving less often because of these concerns. CONCLUSIONS: This study explored
      public transport and car use among a sample of older adults in Singapore to
      access desired activities. It identified difficulties with both public and
      private transportation use, such as difficulty maintaining balance/obtaining a
      seat, and concerns with decreased ability to respond quickly to traffic
      situations. This study has highlighted that transportation methods should be
      considered in occupational therapy practice with older adults.

PMID- 23551007
TI  - Examining contemporary motor control theories from the perspective of degrees of
      freedom.
AB  - BACKGROUND/AIM: Occupational therapy aims to restore independent living skills
      and to improve social participation for clients; therefore, optimising motor
      ability can be a major goal during intervention in clinical practice. Choosing
      the adequate approach for each client is critical to achieve treatment goals. As
      frame of reference is based on contemporary theories related to human behaviours,
      it is crucial to synthesise current theories of motor control for clinical
      application. In this review, four motor control theories were examined by the
      Bernstein's classical question: redundant degrees of freedom. By addressing the
      central issue in motor control theories, the strengths and weaknesses for each
      theory were discussed in detail. METHODS: Classical literatures were selected for
      each theory and related references were reviewed as evidence to support the
      potential biological plausibility. RESULTS: The research of motor control
      theories have been developed for over centuries, researchers still strive to
      discover how human beings execute movements. To date, motor control theories were
      mainly proposed by three disciplines: biology, psychology and engineering. Each
      discipline has unique perspective to develop solutions for understanding the
      processes behind the execution of movement. CONCLUSION: For occupational
      therapists in clinics, it is imperative to integrate current knowledge and motor
      control theories into practice and to explore new approaches to treat clients
      with motor disability.

PMID- 23551008
TI  - Key principles for confronting the challenges of collaboration in educational
      settings.

PMID- 23551009
TI  - There is no evidence to support or refute the effectiveness of memory
      rehabilitation on memory function or functional abilities in people with multiple
      sclerosis.

PMID- 23551010
TI  - Computer-based cognitive exercises plus group classes for generalisation improved
      verbal memory and use of memory strategies by people with multiple sclerosis.

PMID- 23551011
TI  - Genome-wide association study of pre-eclampsia detects novel maternal single
      nucleotide polymorphisms and copy-number variants in subsets of the Hyperglycemia
      and Adverse Pregnancy Outcome (HAPO) study cohort.
AB  - A genome-wide association study was undertaken to identify maternal single
      nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) associated with
      pre-eclampsia. Case-control analysis was performed on 1070 Afro-Caribbean (n = 21
      cases and 1049 controls) and 723 Hispanic (n = 62 cases and 661 controls) mothers
      and 1257 mothers of European ancestry (n = 50 cases and 1207 controls) from the
      Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. European ancestry
      subjects were genotyped on Illumina Human610-Quad and Afro-Caribbean and Hispanic
      subjects were genotyped on Illumina Human1M-Duo BeadChip microarrays. Genome-wide
      SNP data were analyzed using PLINK. CNVs were called using three detection
      algorithms (GNOSIS, PennCNV, and QuantiSNP), merged using CNVision, and then
      screened using stringent criteria. SNP and CNV findings were compared to those of
      the Study of Pregnancy Hypertension in Iowa (SOPHIA), an independent pre
      eclampsia case-control dataset of Caucasian mothers (n = 177 cases and 116
      controls). A list of top SNPs were identified for each of the HAPO ethnic groups,
      but none reached Bonferroni-corrected significance. Novel candidate CNVs showing
      enrichment among pre-eclampsia cases were also identified in each of the three
      ethnic groups. Several variants were suggestively replicated in SOPHIA. The
      discovered SNPs and copy-number variable regions present interesting candidate
      genetic variants for pre-eclampsia that warrant further replication and
      investigation. 

PMID- 23551012
TI  - Association between umbilical cord artery pCO2 and the Apgar score; elevated
      levels of pCO2 may be beneficial for neonatal vitality after moderate acidemia.
AB  - OBJECTIVE: To determine the association between 5-min Apgar score and umbilical
      cord artery carbon dioxide tension (pCO2). DESIGN: Observational study. SETTING:
      European hospital labor wards. POPULATION: Data from 36,432 newborns >=36
      gestational weeks were obtained from three sources: two trials of monitoring with
      fetal electrocardiogram (the Swedish randomized controlled trial and the European
      Union Fetal ECG trial) and Molndal Hospital data. After validation of the acid
      base values, 25,806 5-min Apgar scores were available for analysis. METHODS:
      Validation of the umbilical cord acid-base values was performed to obtain
      reliable data. 5-min Apgar score was regressed against cord artery pCO2 in a
      polynomial multilevel model. MAIN OUTCOME MEASURES: Five-min Apgar score,
      umbilical cord pCO2, pH, and base deficit. RESULTS: Overall, a higher cord artery
      pCO2 was found to be associated with lower 5-min Apgar scores. However, among
      newborns with moderate acidemia, lower umbilical cord artery pCO2 (<=median pCO2
      for the specific cord artery pH) was associated with lower 5-min Apgar scores,
      with a relative risk of 2.0 (95% confidence interval: 1.4-2.8) for 5-min Apgar
      scores 0-6. CONCLUSIONS: Metabolic acidosis affects the newborn's vitality more
      than respiratory acidosis. In addition, elevated levels of pCO2 may be beneficial
      for fetuses with moderate acidemia, and thus cord artery pCO2 is a factor that
      should be considered when assessing the compromised newborn.

PMID- 23551013
TI  - Psychometric and demographic predictors of the perceived risk of terrorist
      threats and the willingness to pay for terrorism risk management programs.
AB  - A 2009 national telephone survey of 924 U.S. adults assessed perceptions of
      terrorism and homeland security issues. Respondents rated severity of effects,
      level of understanding, number affected, and likelihood of four terrorist
      threats: poisoned water supply; explosion of a small nuclear device in a major
      U.S. city; an airplane attack similar to 9/11; and explosion of a bomb in a
      building, train, subway, or highway. Respondents rated perceived risk and
      willingness to pay (WTP) for dealing with each threat. Demographic, attitudinal,
      and party affiliation data were collected. Respondents rated bomb as highest in
      perceived risk but gave the highest WTP ratings to nuclear device. For both
      perceived risk and WTP, psychometric variables were far stronger predictors than
      were demographic ones. OLS regression analyses using both types of variables to
      predict perceived risk found only two significant demographic predictors for any
      threat--Democrat (a negative predictor for bomb) and white male (a significant
      positive predictor for airline attack). In contrast, among psychometric
      variables, severity, number affected, and likelihood were predictors of all four
      threats and level of understanding was a predictor for one. For WTP, education
      was a negative predictor for three threats; no other demographic variables were
      significant predictors for any threat. Among psychometric variables, perceived
      risk and number affected were positive predictors of WTP for all four threats;
      severity and likelihood were predictors for three; level of understanding was a
      significant predictor for two.

PMID- 23551014
TI  - Autoimmune epilepsy in children: case series and proposed guidelines for
      identification.
AB  - PURPOSE: Antibodies against neuronal surface proteins are increasingly recognized
      in autoimmune central nervous system (CNS) disorders in which seizures are the
      main or an important feature. The disorders include antibody-associated limbic
      encephalitis and N-methyl-D-aspartate receptor (NMDAR) encephalitis; however,
      seizures of autoimmune etiology may exist beyond the spectrum of these recognized
      syndromes. Because these seizures are potentially treatable with immune therapy,
      guidelines are needed to help in their early recognition. METHODS: We describe 13
      representative children seen at our tertiary institution over a period of 3.5
      years with suspected autoimmune epilepsy. Autoimmune epilepsy was suspected
      clinically when there was any of the following: (1) recognizable syndromes such
      as NMDAR encephalitis or limbic encephalitis, (2) evidence of CNS inflammation in
      cerebrospinal fluid or on magnetic resonance imaging (MRI), (3) the presence of
      other autoimmune diseases, or (4) positive response to immunotherapy. We tested
      these patients for neuronal surface antibodies (voltage gated potassium channel
      [VGKC]-complex, leucine rich glioma inactivated 1 [LGI1], contactin-associated
      protein-like 2 [CASPR2], and NMDAR) and glutamic acid decarboxylase (GAD)
      antibodies. We modified the J Neurol Neurosurg Psychiatry, 83, 2012, 638
      guidelines that were designed to classify adults with neuronal surface antibody
      syndromes (NSAS), to be more appropriate for children with suspected autoimmune
      epilepsy. Using the modified guidelines, the 13 patients were classified into
      definite, probable, possible, unlikely, or unknown autoimmune epilepsy according
      to the presence of neuronal surface or GAD antibodies, and the response to immune
      therapy when given. KEY FINDINGS: Of the 13 patients, 11 were females, and the
      mean age was 6 years (range 1-13 years). Three patients had classical NMDAR
      encephalitis, two had VGKC encephalitis, two had limbic encephalitis with
      negative antibodies, three had epilepsy with other autoimmune diseases (one with
      high titer GAD antibodies), two had fever-induced refractory epileptic
      encephalopathy in school-aged children (FIRES), and one epileptic encephalopathy
      associated with VGKC antibodies. Seven patients of the 13 children with suspected
      autoimmune epilepsy were positive for neuronal surface antibodies (NMDAR, n = 3;
      VGKC-complex, n = 3; and GAD, n = 1). Immunotherapy was given to nine cases, and
      a positive response was more common in patients with positive neuronal surface
      antibodies (5/5) compared to those with negative antibodies (2/4). Applying the
      proposed guidelines, the classification of autoimmune epilepsy was definite in
      five, probable in one, possible in three, unlikely in two, and unknown in two
      patients. SIGNIFICANCE: Neuronal surface antibodies and GAD antibodies are
      present in a proportion of children with suspected autoimmune epilepsy and may
      define a treatable subgroup of childhood epilepsy. The proposed guidelines can be
      useful in the recognition of children with seizures of autoimmune etiology.

PMID- 23551015
TI  - Rhodobacteraceae are the key members of the microbial community of the initial
      biofilm formed in Eastern Mediterranean coastal seawater.
AB  - The formation of biofilms and biofouling is a common feature in aquatic
      environments. The aim of this study was to identify the primary colonizers of
      biofilm formed in Eastern Mediterranean Coastal water at different seasons and
      follow early dynamics of biofilm community development. Pre-treated coastal
      seawater and biofilm samples were collected from six different sampling events of
      2 weeks' duration each during 1 year. The microbial community composition and
      specific abundance were estimated by 16S rRNA gene clone libraries and
      fluorescence in situ hybridization-confocal laser scanning microscopy (FISH
      CLSM), respectively. The biofilm formed over the course of the year was fairly
      consistent in terms of community composition and overall abundance with the
      exception of spring season. Alphaproteobacteria (30-70% of total bacteria), in
      particular Rhodobacteraceae, were the dominant bacteria in the biofilm,
      regardless of season, followed by Bacteroidetes (5-35%) and Gammaproteobacteria
      (6-35%). There was a decrease in relative abundance of Alphaproteobacteria and an
      increase in the abundance of Bacteroidetes between the initial and 2-week-old
      biofilm. This observation may aid man-made facilities that have to deal with
      biofilm formation and help the development of appropriate strategies to control
      those biofilms.

PMID- 23551016
TI  - Biographical value: towards a conceptualisation of the commodification of illness
      narratives in contemporary healthcare.
AB  - Illness narratives play a central role in social studies of health and illness,
      serving as both a key theoretical focus and a popular research method. Despite
      this, relatively little work has gone into conceptualising how and why illness
      narratives - be they in books, websites, television or other media - are
      commodified in contemporary healthcare and its social environment; namely, how
      distinctive forms of value are generated in the production, circulation, use and
      exchange of illness narratives. In this article we propose the notion of
      biographical value as a first step towards conceptualising the values attributed
      to illness narratives in this context. Based on a secondary analysis of 37
      interviews with people affected by 15 different health conditions in the UK (all
      of whom have shared their illness experiences across various media) and drawing
      on understandings of value in research on the bioeconomy and the concept of
      biovalue in particular, we sketch out how epistemic, ethical and economic forms
      of value converge and co-constitute each other in the notion of biographical
      value and in broader economies of illness experiences. 

PMID- 23551017
TI  - Quantum dot-based, quantitative, and multiplexed assay for tissue staining.
AB  - The excellent optical properties of quantum dots (QDs), such as high brightness,
      high photostability, continuous absorption, and narrow emission bandwidth, make
      them ideal as optical labels to develop QD-based immunohistofluorescence (IHF)
      imaging for multiplexing cancer biomarker detection on formalin-fixed and
      paraffin-embedded (FFPE) tissues. IHF is very important for the prediction of a
      patient's response to cancer chemotherapy or radiotherapy. QD-based IHF faces
      several challenges that differ from those encountered by organic dye based IHF
      for clinical assays. The current work addresses some of these issues. Initially,
      the chemical stability of QDs and organic dyes were compared. The results showed
      that QDs were stable for at least 5 months on FFPE tissue, whereas organic dyes
      were photobleached shortly after exposure to light. Various staining methods were
      also studied. QD fluorescence intensity on the tissue stained with primary
      antibody (Ab, p16, survivin, EF1alpha) conjugated QDs from our company was
      comparable to the signal from a commercially available method in which the tissue
      was stained with a primary p16 Ab and a QD-labeled secondary goat anti mouse Ab
      respectively. Finally, the effect of the amount of Ab conjugated to QD on tissue
      imaging was also studied. There was no significant increase in the QD
      fluorescence signal on tissues when the Ab:QD ratio increased from 5 to 30. In
      addition, protein G was tested as an adaptor protein to link Ab to QDs for IHF
      staining. However, the proper blocking of the protein G on QDs was necessary to
      reduce crosstalk. The biomarker quantification in QD-based IHF was validated by
      conventional Western blot and immunohistochemistry. The results contained herein
      demonstrate a promising application of QDs in multiplex detection and
      quantification of biomarkers.

PMID- 23551018
TI  - Five questions in chronic obstructive pulmonary disease.

PMID- 23551019
TI  - How can we define well-controlled chronic obstructive pulmonary disease?
AB  - The main objectives in the management of chronic disorders such as chronic
      obstructive pulmonary disease (COPD) are: to suppress or minimize symptoms; to
      prevent and reduce exacerbations; to avoid limitations in activities of daily
      living, and thus to enable the patient to lead a normal, or nearly normal, life.
      COPD has become a serious public-health concern. The disease, which may be life
      threatening if not properly managed, often goes undiagnosed. COPD accounts for
      significant healthcare, social and personal costs, as it can cause disability and
      lead to marked impairment in patients' quality of life. The primary goal in the
      management of COPD should be to maintain patients' clinical stability so as to
      lessen the impact of the disease. This implies achieving an adequate patient
      control with as few limitations of everyday activities as possible. In an attempt
      to optimize their quality of life, patients should be symptom-free or virtually
      symptom-free. In addition, exacerbations, which involve a high consumption of
      both healthcare and personal resources, must be prevented. COPD is the fourth
      leading cause of death among men in Europe. As its prevalence is expected to
      increase, it might become the third cause of mortality by 2030. In Spain, COPD
      management has recently been reviewed in the Spanish COPD Guidelines (GesEPOC).
      The COPD National Health System Strategy, developed by the Spanish Ministry of
      Health, Social Policy and Equality under the Quality Plan, aims at implementing a
      set of measures to improve both the efficacy and the quality of healthcare
      services for patients with COPD.

PMID- 23551021
TI  - How and when to use inhaled corticosteroids in chronic obstructive pulmonary
      disease?
AB  - Inhaled corticosteroids (ICSs) are widely used in chronic obstructive pulmonary
      disease (COPD). Since inflammatory processes play a key role in the pathogenesis
      of the disease and ICSs have been shown to be very effective in controlling
      asthma, their use in COPD patients has become widespread. However, their efficacy
      in COPD is more limited than in asthma, since the type of inflammation in COPD is
      predominantly neutrophilic and resistant to corticosteroids. ICSs have not been
      shown to prevent disease progression or reduce mortality in clinical trials. By
      contrast, these agents reduce exacerbations and improve both symptoms and quality
      of life in selected patients, particularly those with bronchial reversibility.
      Since ICSs are not harmless drugs, clinicians should make every effort to
      distinguish patients who will benefit from ICS treatment from those who will not.
      Side effects of ICSs may be both local and systemic, with most of them being dose
      dependent. A potential increase in the risk of pneumonia, diabetes, dysphonia or
      candiadiasis, among other complications, should be considered when prescribing
      these drugs in patients who usually have several comorbidities. Hence, it is
      important to identify those patients in whom the best risk-to-benefit ratio can
      be achieved and to use the most appropriate ICS dose with the least incidence of
      side effects.

PMID- 23551020
TI  - Which is the optimal bronchodilator therapy for chronic obstructive pulmonary
      disease?
AB  - Chronic obstructive pulmonary disease is an inflammatory disorder characterized
      by airflow limitation. Its cardinal symptom is dyspnea, which develops gradually
      with even low levels of exercise. Bronchodilators (BDs) are the most effective
      drugs for relieving dyspnea. Two main types of BD are currently available, beta
      mimetics and anticholinergics, with different subtypes according to their
      duration of action. The most useful agents are those administered once daily,
      also called 'ultralong-acting' BDs. As a high proportion of patients remain
      insufficiently controlled with only one BD, all guidelines currently recommend
      the combination of two long-acting agents. A number of studies have demonstrated
      that combination therapy is functionally and, in general, clinically superior to
      individual drugs. Although various combinations have been assessed, the current
      trend is to use ultralong-acting agents due to their more convenient dosing
      schedule and, probably, their greater efficacy. In the research setting, some of
      these agents are combined in a single device, an approach that may become the
      standard treatment for many patients with chronic obstructive pulmonary disease.

PMID- 23551022
TI  - How should we define and classify exacerbations in chronic obstructive pulmonary
      disease?
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic disorder whose clinical
      course may be punctuated by exacerbations characterized by a sudden symptom
      worsening beyond the expected daily variations. Exacerbations bear clinical and
      prognostic relevance, and may result in marked functional and clinical
      deterioration. The varying presentations of COPD mean that exacerbations,
      although more frequent in patients with severe or very severe disease, may occur
      regardless of the degree of functional impairment. The new Spanish COPD Guideline
      (GesEPOC) has provided new insights into the management of the disease. The
      GesEPOC defines various disease phenotypes with different clinical, prognostic
      and therapeutic implications. One of these phenotypes is the so-called
      'exacerbator', characterized by the incidence of an increased number of
      exacerbations (two or more moderate-severe exacerbations in the last year). An
      exacerbation must be defined by: an increase in symptom intensity occurring after
      a certain period of time since the last exacerbation (so that treatment failure
      can be excluded as the cause of the event); and the contribution of social
      criteria or reasons concerning the choice of therapy. The availability of certain
      tools to detect exacerbations would enable establishment of a homogeneous
      definition of exacerbation, and improved diagnosis, a suitable treatment choice
      and a more appropriate patient selection for clinical studies. Validated clinical
      questionnaires and biomarkers are the most helpful instruments to reach the above
      objectives. Following the clinical diagnosis of a COPD exacerbation, associated
      comorbidities must be evaluated and an etiologic diagnosis must be made, all of
      which will partially drive the choice of treatment. Once a diagnosis has been
      made, the severity of the exacerbation should be established in order to define
      where and how the patient should be treated. Based on the patient's clinical
      history, clinical examination and diagnostic tests, the severity will be
      classified in one of these four degrees: very severe, severe, moderate and mild.

PMID- 23551023
TI  - What is in the guidelines about the pharmacological treatment of chronic
      obstructive pulmonary disease?
AB  - With the publication of the new guidelines (The Global Initiative for Chronic
      Obstructive Lung Disease 2011 and Guia Espanola de la COPD) on chronic
      obstructive pulmonary disease (COPD), the pharmacological treatment of this
      disease has changed substantially. In this article, the evidence supporting the
      use of pharmacological groups in COPD is summarized and the place of each of
      these drugs among the new therapeutic strategies is established. Although short
      acting bronchodilators have been used as maintenance therapy for COPD for many
      years, few clinical trials are available on the efficacy and safety of these
      agents, whose role was defined at the very early stages of treatment. The
      introduction of long-acting bronchodilators, administered every 12 or 24 h, led
      to an increase in therapeutic effects and an improvement in both treatment
      adherence and dosage; therefore, both guidelines consider these drugs as the
      standard therapy for all types of patients and clinical phenotypes. The
      combination of long-acting bronchodilators from different families has been
      established as a new therapeutic approach for patients with persistent symptoms
      despite an appropriate bronchodilator treatment. Anti-inflammatory therapy with
      inhaled corticosteroids has been discussed at length, and is considered in the
      current guidelines as the treatment of choice in patients with a high risk of
      exacerbations associated with an impaired lung function or previous
      exacerbations, or presenting with phenotypes that are susceptible to the effect
      of corticosteroids. Roflumilast is a novel drug with a clearly defined
      indication. Finally, further evidence about other therapies, such as antibiotics
      or mucolytics, is emerging that will help define their appropriate use in
      selected patients. At present, pharmacological management of COPD is being re
      evaluated. As long as we are able to apply the new treatment approaches to the
      clinical reality of our patients we will achieve greater benefits in both the
      short and the long term with a reduction in potential complications.

PMID- 23551024
TI  - Variability in personality expression across contexts: a social network approach.
AB  - The current research investigated how the contextual expression of personality
      differs across interpersonal relationships. Two related studies were conducted
      with college samples (Study 1: N = 52, 38 female; Study 2: N = 111, 72 female).
      Participants in each study completed a five-factor measure of personality and
      constructed a social network detailing their 30 most important relationships.
      Participants used a brief Five-Factor Model scale to rate their personality as
      they experience it when with each person in their social network. Multiple
      informants selected from each social network then rated the target participant's
      personality (Study 1: N = 227, Study 2: N = 777). Contextual personality ratings
      demonstrated incremental validity beyond standard global self-report in
      predicting specific informants' perceptions. Variability in these contextualized
      personality ratings was predicted by the position of the other individuals within
      the social network. Across both studies, participants reported being more
      extraverted and neurotic, and less conscientious, with more central members of
      their social networks. Dyadic social network-based assessments of personality
      provide incremental validity in understanding personality, revealing dynamic
      patterns of personality variability unobservable with standard assessment
      techniques. 

PMID- 23551025
TI  - Promoting happiness: the malleability of individual and societal subjective
      wellbeing.
AB  - Is it possible to enhance the subjective wellbeing of individuals and societies?
      If so, what are the mental health interventions and economic mechanisms by which
      subjective wellbeing could be enhanced? We address these questions in our review
      of the literature on subjective wellbeing. Research now shows that although
      subjective wellbeing is heritable and stable, it can change substantially over
      time. Long-term changes can be affected by positive or negative life events;
      subjective wellbeing interventions have also proved to be effective for boosting
      wellbeing for as long as six months. At the societal level, economic factors
      matter for the subjective wellbeing of citizens. Economic wealth is shown to be a
      predictor of societal wellbeing across countries and over time. Also, high
      unemployment severely lowers the wellbeing of individuals and has spillover
      effects on other societal members, such as the employed. Given the weight of
      evidence, we are optimistic that subjective wellbeing can be enhanced. For
      practitioners, policy makers, and economists interested in the wellbeing of
      individuals, we propose that these findings have implications for mental health
      practice and economic policies. Future research and methodological issues are
      discussed. 

PMID- 23551026
TI  - Comment on "An interesting case where water behaves as a unique solvent. 4
      Aminophthalimide emission profile to monitor aqueous environment".

PMID- 23551027
TI  - Consolidation and transfer of learning after observing hand gesture.
AB  - Children who observe gesture while learning mathematics perform better than
      children who do not, when tested immediately after training. How does observing
      gesture influence learning over time? Children (n = 184, ages = 7-10) were
      instructed with a videotaped lesson on mathematical equivalence and tested
      immediately after training and 24 hr later. The lesson either included speech and
      gesture or only speech. Children who saw gesture performed better overall and
      performance improved after 24 hr. Children who only heard speech did not improve
      after the delay. The gesture group also showed stronger transfer to different
      problem types. These findings suggest that gesture enhances learning of abstract
      concepts and affects how learning is consolidated over time.

PMID- 23551028
TI  - Short communication: high natural polymorphism in the gag gene cleavage sites of
      non-B HIV type 1 isolates from Gabon.
AB  - The main goal of the present study was to determine the frequency of
      substitutions in the cleavage sites (CS) of gag gene among non-B HIV-1 isolates
      from Gabon. Fifty plasma specimens, collected in 2010-2011, from HIV-1-infected
      patients failing first-line antiretroviral (ARV) regimens (constituted of two
      nucleoside reverse transcriptase inhibitors+one nonnucleoside reverse
      transcriptase inhibitor) (n=38) and from HIV-1-infected individuals untreated
      with ARV (n=12) were analyzed in the gag and gag-pol cleavage sites. Compared to
      HXB2 reference sequence, the total median number of substitutions in gag and gag
      pol CS was 10 (range, 5-18). The cleavage site p2/NC was the most variable of the
      four gag CS with 100% (50/50) isolates carrying at least 1 substitution (range, 1
      9). The two gag-pol TFP/p6pol and p6pol/PR CS sites were also highly variable (at
      least one substitution, 50/50, 100% in both cases). Substitutions at position
      G381 (p2/NC), L449 (p1/p6gag), and K444 (TFP/p6pol) were significantly more
      frequent in CRF02_AG strains, compared to other non-B strains (30.4% vs. 3.7%,
      p=0.03; 87.0% vs. 59.3%, p=0.03; and 91.3% vs. 59.3%, p=0.01, respectively).
      Other non-B subtypes were significantly more likely to harbor substitutions at
      position N487 (p6pol) (70.4%) than CRF02_AG (39.1%) (p=0.02). In Gabon, gag and
      gag-pol cleavage sites were highly polymorphic in protease inhibitor-naive
      patients harboring non-B HIV-1 strains. In sub-Saharan Africa, further studies
      are definitively required to better understand the impact of gag mutations among
      subjects receiving second-line LPV/r-containing regimens (monotherapy or triple
      combinations).

PMID- 23551029
TI  - Patient satisfaction with mini-implant stabilised full dentures. A 1-year
      prospective study.
AB  - The purpose of this study was to evaluate patient-centred outcomes with regard to
      function and comfort after placement of mini-implants for stabilisation of
      complete dentures. The trial was designed as a prospective cohort of 12-months
      duration and involved 21 subjects in the age of 50-90 years having a full denture
      in the maxilla or the mandible with poor stability during function. Flapless
      installation of 2-4 narrow-body Dentatus Atlas((r)) implants was performed and
      retention for the existing denture was obtained by the use of a silicone-based
      soft lining material (Tuf-Link((r))). Patients' judgement of perceived
      satisfaction with function and comfort of the dentures was recorded at baseline,
      1- and 12-months post-treatment using 10-centimetre visual analogue scales (VAS)
      and a questionnaire. Clinical examination of the conditions of the peri-implant
      soft tissues was performed at 12 months. Nineteen of the 21 patients were
      available for the 12-month follow-up examination. The two drop-out subjects lost
      all implants within 1 month and rejected retreatment. Further six subjects lost 1
      2 implants, but were sucessfully retreated by insertion of new implants. Overall
      satisfaction, chewing and speaking comfort were all markedly improved from pre
      treatment median VAS scores of around 4-5 to median scores of 9.0-10 (10 =
      optimal) at the final examination. The prevalence of positive answers to
      questions regarding stability/function of the denture increased significantly to
      almost 100% for all questions. Treatment involving maxillary dentures and the use
      of short implants (7-10 mm) was associated with an increased risk of implant
      failure. The results indicate that placement of mini-implants as retentive
      elements for full dentures with poor functional stability has a marked positive
      impact on the patients' perception of oral function and comfort as well as
      security in social life.

PMID- 23551030
TI  - Cleaner cooking solutions to achieve health, climate, and economic cobenefits.
AB  - Nearly half the world's population must rely on solid fuels such as biomass
      (wood, charcoal, agricultural residues, and animal dung) and coal for household
      energy, burning them in inefficient open fires and stoves with inadequate
      ventilation. Household solid fuel combustion is associated with four million
      premature deaths annually; contributes to forest degradation, loss of habitat and
      biodiversity, and climate change; and hinders social and economic progress as
      women and children spend hours every day collecting fuel. Several recent studies,
      as well as key emerging national and international efforts, are making progress
      toward enabling wide-scale household adoption of cleaner and more efficient
      stoves and fuels. While significant challenges remain, these efforts offer
      considerable promise to save lives, improve forest sustainability, slow climate
      change, and empower women around the world.

PMID- 23551031
TI  - Evolution of the psychological autopsy: fifty years of experience at the Los
      Angeles County Chief Medical Examiner-Coroner's Office.
AB  - The origin of the psychological autopsy was in the late 1950s and the result of a
      collaboration between the Los Angeles County Chief Medical Examiner-Coroner's
      Office and the Los Angeles Suicide Prevention Center. It was conceptualized as a
      thorough retrospective analysis of the decedent's state of mind and intention at
      the time of death. It was used initially in "equivocal" deaths where the manner
      of death was possibly either suicide or accident. Later, it was used in cases
      where a party (primarily family members) protested the Medical Examiner-Coroner's
      suicide determination. Over the past 25 years, the University of Southern
      California Institute of Psychiatry, Law, and Behavioral Science has served as the
      psychiatric/psychological consultants to the Coroner's Department. Research
      findings, the use of this approach in high-profile cases, and the most recent
      manner in which the psychological autopsy is conducted are discussed.

PMID- 23551032
TI  - Squish and CuAAC: additive-free covalent monolayers of discrete molecules in
      seconds.
AB  - A terminal alkyne is immobilized rapidly into a full monolayer by squishing a
      small volume of a solution of the alkyne between an azide-modified surface and a
      copper plate. The monolayer is covalently attached to the surface through a
      copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, and the coverages
      of the immobilized electroactive alkyne species are quantified by cyclic
      voltammetry. A reaction time of less than 20 s is possible with no other reagents
      required. The procedure is effective under aerobic conditions using either an
      aqueous or aprotic organic solution of the alkyne (1-100 mM).

PMID- 23551033
TI  - Hand-assisted laparoscopic total pancreatectomy: a report of two cases.
AB  - BACKGROUND: Because of improvement in surgical technique and endocrine and
      exocrine insufficiency management, total pancreatectomy is being frequently
      performed, especially for benign or low-potential malignant diseases. The
      laparoscopic approach is rarely performed. SUBJECTS AND METHODS: Our aim is to
      report two cases operated by the assisted laparoscopic approach and to describe a
      standardized surgical technique. RESULTS: Two patients underwent laparoscopic
      total pancreatectomy with assisted minilaparotomy or the hand-assisted technique
      for degenerated intraductal papillary mucinous neoplasms (IPMNs) and
      neuroendocrine tumors with operative times of 270 and 360 minutes, estimated
      blood loss of 200 and 300 mL, and a hospital stay of 12 and 18 days,
      respectively. One patient was re-operated on postoperative Day 10 for bleeding
      from the hepaticojejunostomy probably related to an inadequate dose of antiproton
      inhibitors, necessitating refection of the anastomosis with an uneventful course.
      Pathological examination revealed degenerated IPMNs (T3N1R0) and well
      differentiated neuroendocrine tumors (T2NOR0) with complete resection. After 6-10
      months of follow-up, the diabetes is well controlled with insignificant episodes
      of hypoglycemia in 1 patient without any evidence of tumor relapse. CONCLUSIONS:
      In selected patients laparoscopic total pancreatectomy appears safe and had many
      advantages over the open and other laparoscopic pancreatic resection approaches,
      including first laparoscopic abdominal exploration and no pancreatic anastomosis.
      Oncological rules can be respected, but further larger studies are needed before
      drawing conclusions.

PMID- 23551034
TI  - Systemic psoriasis therapy shows high between-country variation: a sign of
      unwarranted variation? Cross-sectional analysis of baseline data from the PSONET
      registries.

PMID- 23551035
TI  - Teaching case: hypertensiveheadache.

PMID- 23551036
TI  - Hyperprolactinaemia associated with increased thyroid volume and autoimmune
      thyroiditis in patients with prolactinoma.
AB  - OBJECTIVE: The aim of this investigation was to evaluate the effects of
      hyperprolactinaemia on thyroid function, volume and nodularity in patients with
      prolactinoma. CONTEXT: Hyperprolactinaemia has been associated with various
      autoimmune diseases; however, the data on the correlation between the level of
      prolactin (PRL) and thyroid disorders have not been adequately clarified. DESIGN:
      Case-control study. PATIENTS: Forty-eight subjects with new diagnosis of
      hyperprolactinaemia (group 1) and 39 subjects undergoing treatment for
      prolactinoma (group 2) were recruited from our outpatient clinic. Fifty-two
      healthy subjects were included as a control group (group 3). MEASUREMENTS: The
      serum PRL, thyroid-stimulating hormone (TSH), thyroxine (free T4), thyroidal
      microsome (anti-TPO) and antithyroglobulin antibodies (TgAb) levels were
      evaluated, and ultrasonographic thyroid volume was calculated. RESULTS: The
      frequencies of positive anti-TPO and TgAb were significantly higher in group 1
      than in groups 2 and 3 (P = 0.008). Also, the percentage of patients with thyroid
      heterogeneity were significantly higher in groups 1 and 2 than in group 3 (P <
      0.05). The percentage of patients with thyroid nodules were higher in group 1
      than in groups 2 and 3 (p1-2 = 0.03, p1-3 = 0.05 and p2-3 = 0.637). The mean
      thyroid volume was significantly higher in group 1 (P = 0.001), and a positive
      correlation was found between thyroid volume and the level of PRL (r = 0.616; P =
      0.0001). Prolactin had a significant effect on the total volume according to
      stepwise multiple linear regression analysis (adjusted R(2) is 0.268; P <
      0.0001). CONCLUSIONS: Patients with hyperprolactinaemia have significantly
      increased thyroid volume, thyroid autoimmunity and nodule prevalence.

PMID- 23551037
TI  - Moderation of a parent-based intervention on transitions in drinking: examining
      the role of normative perceptions and attitudes among high- and low-risk first
      year college students.
AB  - BACKGROUND: Parent-based interventions (PBIs) are an effective strategy to reduce
      problematic drinking among first-year college students. The current study
      examined the extent to which student-based characteristics, derived from the
      Theory of Planned Behavior, moderated 3 PBI conditions: (i) prior to college
      matriculation (PCM); (ii) PCM with a booster during the fall semester; and (iii)
      after college matriculation. The moderator variables included injunctive and
      descriptive peer norms about alcohol use and attitudes toward alcohol use.
      METHODS: Using data from a randomized control trial delivered to 1,900 incoming
      college students, we examined differential treatment effects within 4 types of
      baseline student drinkers: (i) nondrinkers; (ii) weekend light drinkers (WLD);
      (iii) weekend heavy episodic drinkers; and (iv) heavy drinkers. The outcome
      variable was based on the transitions in drinking that occurred between the
      summer prior to college enrollment and the end of the first fall semester and
      distinguished between students who transitioned to 1 of the 2 risky drinking
      classes. RESULTS: The results indicated that injunctive norms (but not
      descriptive norms or attitudes) moderated the differential effects of the PBI
      with strongest effects for students whose parents received the booster.
      Differential effects also depended on baseline drinking class and were most
      pronounced among WLDs who were deemed "high-risk" in terms of injunctive peer
      norms. CONCLUSIONS: Parental influence can remain strong for young adults who are
      transitioning to college environments, even among students with relatively high
      peer influence to drink alcohol. Thus, the PBI represents an effective tool to
      prevent escalation of alcohol use during the first year of college, when risk is
      highest and patterns of alcohol use are established.

PMID- 23551038
TI  - Impact of processing parameters on the phenolic profile of wines produced from
      hybrid red grapes Marechal Foch, Corot noir, and Marquette.
AB  - Phenolic extraction in hybrid and interspecific wine grape cultivars is poorly
      understood, especially in terms of the impact of fermentation and enological
      conditions on condensed tannins and anthocyanins. Following fractionation via
      solid-phase extraction and high-performance liquid chromatography, phenolic
      profiles of must and wine from red hybrid grape cultivars Marechal Foch, Corot
      noir, and Marquette were examined to assess the impact of enzyme and tannin
      addition, cold soak, and hot press during vinification. Across cultivars, hot
      press treatments resulted in the greatest extraction of condensed tannin,
      anthocyanin, and other monomeric phenolic compounds in musts, and treatments that
      increased skin contact time or cellular degradation during fermentation produced
      higher concentrations of tannins, anthocyanins, and flavonols. However, these
      increases were transient, evincing incomplete carryover into finished wines.
      Depending on initial must extraction, diglucoside forms of anthocyanins were
      either selectively extracted or selectively retained throughout fermentation when
      compared to their monoglucoside counterparts. Typical of hybrid grapes, tannin
      concentrations across cultivars were low, even under hot press conditions. For
      condensed tannins and anthocyanins, a cultivar-specific, stable-state
      concentration and phenolic profile emerged regardless of fermentation conditions.
      Due to the high levels of diglucoside anthocyanins and low levels of condensed
      tannins, it is expected that the color development and profile in these wines
      produced from hybrid grape cultivars will be dictated by the monomeric
      anthocyanins and their potential role in copigmentation processes involving other
      monomeric phenolic species, as opposed to the formation of polymeric color
      pigments.

PMID- 23551040
TI  - Effect of long-term castration on serum biochemistry in rhesus monkeys.
AB  - BACKGROUND: Testicular failure has an effect on normal physiology. To address
      this issue, an experimental non-human primate model of long-term castrated rhesus
      monkey was chosen for this study to evaluate the influence of castration on
      various biochemical parameters. METHODS: Nine castrated rhesus monkeys were
      evaluated for changes in body weight, serum testosterone, and serum biochemical
      parameters as compared to those in non-castrated macaques. RESULTS: Castration
      caused statistically significant changes in body weight, biochemical analytes,
      and testosterone levels. Body weight and testosterone levels were decreased, and
      there were increase in alanine aminotransferase, cholesterol, serum bilirubin,
      phosphorous, alkaline phosphatase, urea and a decrease in serum protein, uric
      acid, creatinine, and triglycerides. CONCLUSIONS: This study provided essential
      baseline information on biochemical variables due to the effect of castration
      associated with declining levels of testosterone, as data are not readily
      accessible from the existing body of scientific literature on non-human primates.

PMID- 23551039
TI  - Wilson disease mutation pattern with genotype-phenotype correlations from Western
      India: confirmation of p.C271* as a common Indian mutation and identification of
      14 novel mutations.
AB  - Wilson disease (WD) is an autosomal recessive disorder resulting from mutations
      in the ATP7B gene, with over 600 mutations described. Identification of mutations
      has made genetic diagnosis of WD feasible in many countries. The heterogeneity of
      ATP7B mutants is, however, yet to be identified in the Indian population. We
      analyzed the mutational pattern of WD in a large region of Western India. We
      studied patients (n = 52) for ATP7B gene mutations in a cohort of families with
      WD and also in first-degree relatives (n = 126). All 21 exon-intron boundaries of
      the WD gene were amplified and directly sequenced. We identified 36 different
      disease-causing mutations (31 exonic and five intronic splice site variants).
      Fourteen novel mutations were identified. Exons 2, 8, 13, 14, and 18 accounted
      for the majority of mutations (86.4%). A previously recognized mutation, p.C271*,
      and the novel mutation p.E122fs, were the most common mutations with allelic
      frequencies of 20.2% and 10.6%, respectively. Frequent homozygous mutations
      (58.9%) and disease severity assessments allowed analysis of genotype-phenotype
      correlations. Our study significantly adds to the emerging data from other parts
      of India suggesting that p.C271* may be the most frequent mutation across India,
      and may harbor a moderate to severely disabling phenotype with limited
      variability. 

PMID- 23551041
TI  - When precaution creates misunderstandings: the unintended effects of
      precautionary information on perceived risks, the EMF case.
AB  - In the past decade, growing public concern about novel technologies with
      uncertain potential long-term impacts on the environment and human health has
      moved risk policies toward a more precautionary approach. Focusing on mobile
      telephony, the effects of precautionary information on risk perception were
      analyzed. A pooled multinational experimental study based on a 5 * 2 * 2
      factorial design was conducted in nine countries. The first factor refers to
      whether or not information on different types of precautionary measures was
      present, the second factor to the framing of the precautionary information, and
      the third factor to the order in which cell phones and base stations were rated
      by the study participants. The data analysis on the country level indicates
      different effects. The main hypothesis that informing about precautionary
      measures results in increased risk perceptions found only partial support in the
      data. The effects are weaker, both in terms of the effect size and the frequency
      of significant effects, across the various precautionary information formats used
      in the experiment. Nevertheless, our findings do not support the assumption that
      informing people about implemented precautionary measures will decrease public
      concerns. 

PMID- 23551042
TI  - Are ongoing cumulative chronic stressors associated with optimism and pessimism
      in the second half of life?
AB  - This study examined the relationship between ongoing cumulative chronic stressors
      (OCCSs) and optimism and pessimism during the second half of life. The sample
      comprised of 7166 participants who completed the 2006 Health and Retirement
      Study's (HRS) psychosocial questionnaire. The association between OCCSs and
      optimism and pessimism was evaluated among the individuals in the second half of
      life. The number of OCCSs was associated with both optimism and pessimism.
      However, the interaction between OCCSs and age was associated with pessimism
      alone. The relationship between "very upsetting" OCCSs and pessimism was
      significant among midlife and young old, but not among old-old participants. A
      larger number of OCCSs in the second half of life has a deleterious association
      with optimism and pessimism; however, it may be that the large sample allowed
      small effects to become significant. Nevertheless, the association between OCCSs
      and pessimism is regulated by age. Old-old participants maintain a stable level
      of pessimism, which is not related to the number of "very upsetting" OCCSs that
      they reported. Implications of the results are discussed. 

PMID- 23551044
TI  - Mean platelet volume can be affected by many factors and should be assessed
      together with other inflammatory markers.

PMID- 23551043
TI  - A quantitative study of white matter hypomyelination and oligodendroglial
      maturation in focal cortical dysplasia type II.
AB  - PURPOSE: A diagnostic feature of focal cortical dysplasia (FCD) type II on
      magnetic resonance imaging (MRI) is increased subcortical white matter (WM)
      signal on T2 sequences corresponding to hypomyelination, the cause of which is
      unknown. We aimed to quantify WM pathology in FCD type II and any deficiency in
      the numbers and differentiation of oligodendroglial (OL) cell types within the
      dysplasia. METHODS: In 19 cases we defined four regions of interests (ROIs): ROI1
      = abnormal WM beneath dysplasia, ROI2 =dysplastic cortex, ROI3 = normal WM, and
      ROI4 = normal cortex. We quantified axonal and myelin density using
      immunohistochemistry for neurofilament, myelin basic protein and quantified
      mature OL with NogoA, cyclic nucleotide 3-phosphodiesterase (CNPase) and OL
      precursor cell (OPC) densities with platelet derived growth factor receptor
      (PDGFR)alpha, beta and NG-2 in each region. KEY FINDINGS: We observed a
      significant reduction in myelin and axons in the WM beneath dysplasia relative to
      normal WM and there was a correlation between relative reduction of myelin and
      neurofilament in each case. OL and OPC were present in the WM beneath dysplasia
      and although present in lower numbers with most markers, were not significantly
      different from normal WM. Neurofilament and myelin labeling highlighted
      disorganized orientation of fibers in dysplastic cortex but there were no
      significant quantitative differences compared to normal cortex. Clinical
      correlations showed an association between the severity of reduction of myelin
      and axons in the WM of FCD and duration of epilepsy. SIGNIFICANCE: These findings
      indicate a reduction of myelinated axons in the WM of FCD type II rather than
      dysmyelination as the primary pathologic process underlying WM abnormalities,
      possibly influenced by duration of seizures. The range of OPC to OL present in
      FCD type II does not implicate a primary failure of cell recruitment and
      differentiation of these cell types in this pathology.

PMID- 23551045
TI  - Testing new susceptibility genes in the cohort of apparently sporadic
      phaeochromocytoma/paraganglioma patients with clinical characteristics of
      hereditary syndromes.
AB  - BACKGROUND: Phaeochromocytoma (PCC) and paraganglioma (PGL) can occur
      sporadically or as a part of familial cancer syndromes. Red flags of hereditary
      syndromes are young age and multifocal tumours. We hypothesized that such
      patients are candidates for further molecular diagnosis in case of normal results
      in 'classical' genes. MATERIAL AND METHODS: We selected patients with PCC/PGL
      under the age of 40 and/or with multiple tumours. First, we tested the genes RET,
      VHL, NF1, SDHB, SDHC and SDHD. Patients without mutations in these genes were
      tested for mutations in MAX, TMEM127 and SDHAF2. RESULTS: In 153 patients
      included, mutations were detected in the classical genes in 72 patients (47%)
      [RET-22 (14%), VHL-13 (9%), NF1-3 (2%), SDHB-13 (9%), SDHC-3 (2%), SDHD-16 (11%),
      SDHB large deletions- 2 (1%)]. One patient with MAXc.223C>T (p.R75X) mutation was
      detected. It was a male with bilateral, metachronous phaeochromocytomas diagnosed
      in 36 and 40 years of age. Remarkably, he showed in the period before the MAX
      gene was detected, a RET p. Y791F variant. During 10-year follow-up, we did not
      find any thyroid abnormalities. LOH examination of tumour tissue showed somatic
      loss of the wild-type allele of MAX. CONCLUSION: Analysis of the MAX gene should
      be performed in selected patients, especially those with bilateral adrenal
      phaeochromocytoma in whom mutations of the classical genes are absent. Our study
      provides with further support that Y791F RET is a polymorphism.

PMID- 23551046
TI  - Mental health and chaplaincy in the U.S. Veterans affairs and defense
      departments.

PMID- 23551047
TI  - Chaplaincy and mental health in the department of Veterans affairs and department
      of defense.
AB  - Chaplains play important roles in caring for Veterans and Service members with
      mental health problems. As part of the Department of Veterans Affairs (VA) and
      Department of Defense (DoD) Integrated Mental Health Strategy, we used a
      sequential approach to examining intersections between chaplaincy and mental
      health by gathering and building upon: 1) input from key subject matter experts;
      2) quantitative data from the VA / DoD Chaplain Survey (N = 2,163; response rate
      of 75% in VA and 60% in DoD); and 3) qualitative data from site visits to 33 VA
      and DoD facilities. Findings indicate that chaplains are extensively involved in
      caring for individuals with mental health problems, yet integration between
      mental health and chaplaincy is frequently limited due to difficulties between
      the disciplines in establishing familiarity and trust. We present recommendations
      for improving integration of services, and we suggest key domains for future
      research.

PMID- 23551048
TI  - Use and sanctification of complementary and alternative medicine by parents of
      children with cystic fibrosis.
AB  - Complementary and alternative medicine (CAM) use, including spiritual modalities,
      is common in pediatric chronic diseases. However, few users discuss CAM
      treatments with their child's physician. Semi-structured interviews of 25 parents
      of children who have cystic fibrosis (CF) were completed. Primary themes were
      identified by thematic analyses. Most parents (19/25) used at least one CAM
      modality with their child. Only two reported discussing CAM use with their
      child's pulmonologist. Most reported prayer as helpful (81%) and multi-faceted,
      including individual and group prayer; using aromatherapy or scented candles as
      an adjunct for relaxation; and the child's sleeping with a blessed prayer.
      Parents ascribed sacred significance to natural oral supplements. CAM use is
      relevant to the majority of participating parents of children under age 13 with
      CF. Chaplains can play a significant role by reframing prayer's integration into
      chronic disease care, co-creating rituals with pediatric patients, and mediating
      conversations between parents and providers.

PMID- 23551051
TI  - Maintaining a social-emotional intervention and its benefits for
      institutionalized children.
AB  - This article reports the maintenance of one of the largest interventions
      conducted in St. Petersburg (Russian Federation) orphanages for children birth to
      4 years using regular caregiving staff. One orphanage received training plus
      structural changes, another training only, and a third business as usual. The
      intervention produced substantial differences between these institutions on the
      Home Observation for Measurement of the Environment (HOME) Inventory and on the
      Battelle Developmental Inventory scores for children. These institutional
      differences in HOME scores (N = 298) and Battelle scores for children (N = 357)
      departing the institutions for families in St. Petersburg and the United States
      were maintained for at least 6 years after the intervention project. This result
      may be associated with certain features of the intervention and activities
      conducted during the follow-up interval. 

PMID- 23551049
TI  - Is adolescents' religious coping with cystic fibrosis associated with the rate of
      decline in pulmonary function?-A preliminary study.
AB  - Religious coping is associated with health outcomes in adolescents with chronic
      disease. Identifying potentially modifiable spiritual factors is important for
      improving health outcomes. The purpose of this study was to determine if
      associations exist between rate of change in pulmonary function and subsequent
      religious coping by adolescents with cystic fibrosis (CF). Retrospective cohort
      design employing the Brief R-COPE and calculated decline in lung function over a
      three-year period were utilized. Data were obtained for 28 adolescents; median
      age 13.5 years. Use of pleading or negative religious coping was associated with
      a worse clinical trajectory. Pleading may be ineffective as disease progression
      is modifiable through adherence to evidence-based treatments. Given established
      relationships of religious coping with general coping, the effects of declining
      pulmonary function may be broader. Changes in pulmonary function suggest
      opportunities for chaplains to explore options to cognitively reframe negative
      religious coping.

PMID- 23551052
TI  - Increased microbial activity in a warmer and wetter climate enhances the risk of
      coastal hypoxia.
AB  - The coastal zone is the most productive area of the marine environment and the
      area that is most exposed to environmental drivers associated with human
      pressures in a watershed. In dark bottle incubation experiments, we investigated
      the short-term interactive effects of changes in salinity, temperature and
      riverine dissolved organic matter (rDOM) on microbial respiration, growth and
      abundance in an estuarine community. An interaction effect was found for
      bacterial growth, where the assimilation of rDOM increased at higher salinities.
      A 3  degrees C rise in the temperature had a positive effect on microbial
      respiration. A higher concentration of DOM consistently enhanced respiration and
      bacterial abundance, while an increase in temperature reduced bacterial
      abundance. The latter result was most likely caused by a positive interaction
      effect of temperature, salinity and rDOM on the abundance of bacterivorous
      flagellates. Elevated temperature and precipitation, causing increased discharges
      of rDOM and an associated lowered salinity, will therefore primarily promote
      bacterial respiration, growth and bacterivore abundance. Our results suggest a
      positive net outcome for microbial activity under the projected climate change,
      driven by different, partially interacting environmental factors. Thus, hypoxia
      in coastal zones may increase due to enhanced respiration caused by higher
      temperatures and rDOM discharge acting synergistically.

PMID- 23551053
TI  - A Bayes linear Bayes method for estimation of correlated event rates.
AB  - Typically, full Bayesian estimation of correlated event rates can be
      computationally challenging since estimators are intractable. When estimation of
      event rates represents one activity within a larger modeling process, there is an
      incentive to develop more efficient inference than provided by a full Bayesian
      model. We develop a new subjective inference method for correlated event rates
      based on a Bayes linear Bayes model under the assumption that events are
      generated from a homogeneous Poisson process. To reduce the elicitation burden we
      introduce homogenization factors to the model and, as an alternative to a
      subjective prior, an empirical method using the method of moments is developed.
      Inference under the new method is compared against estimates obtained under a
      full Bayesian model, which takes a multivariate gamma prior, where the predictive
      and posterior distributions are derived in terms of well-known functions. The
      mathematical properties of both models are presented. A simulation study shows
      that the Bayes linear Bayes inference method and the full Bayesian model provide
      equally reliable estimates. An illustrative example, motivated by a problem of
      estimating correlated event rates across different users in a simple supply
      chain, shows how ignoring the correlation leads to biased estimation of event
      rates. 

PMID- 23551054
TI  - Effects of maternal smokeless tobacco use on selected pregnancy outcomes in
      Alaska Native women: a case-control study.
AB  - OBJECTIVE: To examine the potential effects of prenatal smokeless tobacco use on
      selected birth outcomes. DESIGN: A population-based, case-control study using a
      retrospective medical record review. POPULATION: Singleton deliveries 1997-2005
      to Alaska Native women residing in western Alaska. METHODS: Hospital discharge
      codes were used to identify potential case deliveries and a random control
      sample. Data on tobacco use and confirmation of pregnancy outcomes were
      abstracted from medical records for 1123 deliveries. Logistic regression was used
      to examine associations between tobacco use and pregnancy outcomes. Adjusted odds
      ratios (OR), 95% confidence intervals (95% CI), and p-values were calculated.
      MAIN OUTCOMES MEASURES: Preterm delivery, pregnancy-associated hypertension, and
      placental abruption. RESULTS: In unadjusted analysis, smokeless tobacco use was
      not significantly associated with preterm delivery (OR 1.44, 95% CI 0.97-2.15).
      After adjustment for parity, pre-pregnancy body mass index, and maternal age, the
      point estimate was attenuated and remained non-significant. No significant
      associations were observed between smokeless tobacco use and pregnancy-associated
      hypertension (adjusted OR 0.92, 95% CI 0.56-1.51) or placental abruption
      (adjusted OR 1.11, 95% CI 0.53-2.33). CONCLUSIONS: Prenatal smokeless tobacco use
      does not appear to reduce risk of pregnancy-associated hypertension or to
      substantially increase risk of abruption. An association between smokeless
      tobacco and preterm delivery could not be ruled out. Components in tobacco other
      than nicotine likely play a major role in decreased pre-eclampsia risk in
      smokers. Nicotine adversely affects fetal neurodevelopment and our results should
      not be construed to mean that smokeless tobacco use is safe during pregnancy.

PMID- 23551055
TI  - Association of E-cadherin single-nucleotide polymorphisms with the increased risk
      of breast cancer: a study in South Indian women.
AB  - BACKGROUND: E-cadherin (CDH1) plays an important role in intercellular adhesion,
      cell signaling, and cellular differentiation. Association of single-nucleotide
      polymorphisms (SNPs) of CDH1 has been identified in a number of epithelial
      malignancies; however, studies related to breast cancer are very few. AIM: To
      investigate the association between CDH1 SNPs and breast cancer risk in south
      Indian women. METHODS: Genotyping of CDH1 functional SNPs (-347G/GA, -160C/A, and
      +54C/T) was carried out on genomic DNA of blood from breast cancer patients
      (n=202) and controls (n=250) of south Indian origin by PCR-sequencing and PCR
      restriction fragment length polymorphism techniques. Haplotype frequencies for
      multiple loci and the standardized disequilibrium coefficient (D') for pairwise
      linkage disequilibrium (LD) were assessed by Haploview Software. RESULTS: The
      frequencies of -160A/A genotypes (p=0.038) and -160A alleles (p=0.046) were
      significantly higher in patients compared to controls. In addition, the frequency
      of the -347GA/-160A/+54C haplotype was also significantly elevated in patients
      (p=0.0238). Strong LD was observed between -347G/GA and +54C/T loci (D'=0.44) in
      patients compared to controls. CONCLUSION: The CDH1 -160C/A polymorphism may
      constitute an inheritable risk factor for breast cancer in south Indian women.

PMID- 23551056
TI  - Variations in the PDCD6 gene are associated with increased uterine leiomyoma risk
      in the Chinese.
AB  - Programmed cell death 6 (PDCD6) participates in T cell receptor, Fas, and
      glucocorticoid-induced programmed cell death. To test the relationship between
      PDCD6 polymorphisms and uterine leiomyomas (UL) risk, we investigated the
      association of two SNPs (rs4957014 and rs3756712) in PDCD6 with UL risk in a case
      control study of 295 unrelated premenopausal UL patients and 436 healthy
      postmenopausal control subjects in a population of China. Genotypes of the two
      SNPs were determined with the use of PCR-restriction fragment length polymorphism
      assay. Significantly increased UL risks were found to be associated with the T
      allele of rs4957014 and the T allele of rs3756712 (p=0.016, odds ratio
      [OR]=1.325, 95% confidence intervals [CI]=1.053-1.668 for rs4957014; p<0.0001,
      OR=1.898, 95% CI=1.457-2.474 for rs3756712, respectively). Increased UL risks
      were associated with them in different genetic models. The present study provided
      evidence that rs4957014 and rs3756712 are associated with UL risk, the results
      indicated that genetic polymorphisms in PDCD6 may contribute to the development
      of UL. 

PMID- 23551057
TI  - Therapeutic brain hypothermia, its mechanisms of action, and its prospects as a
      treatment for epilepsy.
AB  - Cooling the core body temperature to 32-35 degrees C, is almost standard practice
      for conditions such as cardiac arrest in adults, and perinatal hypoxic ischemic
      encephalopathy in neonates. Limited clinical data, and more extensive animal
      experiments, indicate that hypothermia could help control seizures, and could be
      applied directly to the brain using implantable devices. These data have fostered
      further research to evaluate whether cooling would be a viable means to treat
      refractory epilepsy. Although the effect of temperature on cellular physiology
      has long been recognized, with possibly dual effects on pyramidal cells and
      interneurons, the exact mechanisms underlying its beneficial effects, in
      particular in epilepsy, are yet to be discovered. This article reviews currently
      available clinical and laboratory data with a focus on cellular mechanisms of
      action and prospects of hypothermia as a treatment for intractable seizures.

PMID- 23551058
TI  - Hemostatic markers can be pivotal roles of risk factors for new-onset atrial
      fibrillation.

PMID- 23551059
TI  - The use of ultrasound elastography in the assessment of malignancy risk in
      thyroid nodules and multinodular goitres.
AB  - OBJECTIVE: The objective of our work is to use a surgical series to analyse the
      validity of elastography in evaluating the malignancy of thyroid nodules and
      multinodular goitres. PATIENTS AND METHODS: The study examined 156 patients, 134
      women (85.9%) and 22 men (14.1%), who underwent surgery for nodular thyroid
      disease between October 2008, and November 2010. The average age of the patients
      was 52 years (+/-14.42). Thirty-six patients (23.1%) presented with a single
      nodule, and 120 (76.9%) exhibited multinodular goitres. Prior to surgical
      intervention, all patients underwent colour eco-elastography using a qualitative
      five-point ordinal scale for nodule classifications. Test results were analysed
      using a receiver operating characteristic (ROC) curve, and an anatomical
      pathologic examination of surgical specimens was used as a gold standard
      diagnostic tool for comparison. RESULTS: Of the 192 nodules analysed, 28 (14.6%)
      were malignant. Using elastography data, an ROC curve was obtained with an area
      under the curve of 0.662 (+/-0.060) and a 95% confidence interval (CI 95%)
      between 0.545 and 0.779 (P = 0.006). By establishing a cut-off point that
      classified thyroid nodules with an elastographic value greater than or equal to 3
      as malignant, we achieved a sensitivity of 75%, specificity of 45.73%, positive
      predictive value of 19.1% and negative predictive value of 91%. The positive and
      negative likelihood ratios were 1.38 and 0.55, respectively. CONCLUSIONS:
      Ultrasound elastography can provide information regarding malignancy risk in
      thyroid nodules and multinodular goitres. However, the sensitivity and
      specificity values obtained in our study are below those reported by other
      groups, a finding that calls into question the current clinical utility of
      ultrasound elastography.

PMID- 23551060
TI  - Socio-demographic characteristics associated with unplanned pregnancy in New
      Zealand: implications for access to preconception healthcare.
AB  - New Zealand's Chief Science Advisor has recommended weight loss interventions be
      made available to women planning a pregnancy. In a postpartum survey of 723 New
      Zealand women, 44% of all pregnancies were unplanned, and in multivariate
      analysis, younger women, women with less income, women with higher parity, and
      single women were more likely to have an unplanned pregnancy (all P <= 0.002). In
      addition, three-quarters of pregnancies to indigenous Maori and Pacific women
      were unplanned. In conclusion, New Zealand women known to have the highest rates
      of overweight and obesity were also most likely to have unplanned pregnancies,
      thereby preventing their access to any forthcoming preconception weight loss
      programs.

PMID- 23551061
TI  - No evidence for peripheral mechanism attenuating auditory ERPs to self-induced
      tones.
AB  - The N1 and P2 event-related potentials (ERPs) are attenuated when the eliciting
      sounds coincide with our own actions. Although this ERP attenuation could be
      caused by central processes, it may also reflect a peripheral mechanism: the
      coactivation of the stapedius muscle with the task-relevant effector, which
      reduces signal transmission efficiency in the middle ear, reducing the effective
      intensity of concurrently presented tones, which, in turn, elicit lower amplitude
      auditory ERPs. Because stapedius muscle contraction attenuates frequencies below
      2 kHz, no attenuation should occur at frequencies above 2 kHz. A self-induced
      tone paradigm was administered with 0.5, 2.0, and 8.0 kHz pure tones. Self
      induced tones elicited attenuated N1 and P2 ERPs, but the magnitude of
      attenuation was not affected by tone frequency. This result does not support the
      hypothesis that ERP attenuation to self-induced tones are caused by stapedius
      muscle contractions.

PMID- 23551062
TI  - Impact of Bifidobacterium bifidum MIMBb75 on mouse intestinal microorganisms.
AB  - Bifidobacterium bifidum MIMBb75 is a recently identified probiotic. However, its
      distribution along the intestine and impact on resident microbiota is unknown.
      Herein, we established a quantitative real-time polymerase chain reaction assay
      targeting the B. bifidum-specific BopA region for the quantification of B.
      bifidum in feces and used this assay to investigate transit of B. bifidum MIMBb75
      through the murine intestine. We also analyzed the consequential impact on
      resident microbial cohorts. C57BL/6J mice were daily gavaged with 0.2 mL of
      either sterile PBS or PBS containing 10(8) colony-forming units of B. bifidum
      MIMBb75 for 2 weeks, after which intestinal contents and fecal samples were
      analyzed for microbial compositional changes. Bifidobacterium bifidum MIMBb75 was
      able to transiently colonize the murine intestine, with the predominant niche
      being the ceco-proximal colonic region. Region-specific effects on host
      microbiota were observed including decreased levels of Clostridium coccoides in
      the cecum, increased levels of bifidobacteria in the proximal and distal colon,
      total bacteria and Clostridium leptum in the proximal colon, and of C. coccoides
      in the feces. These findings suggest that probiotic properties of B. bifidum
      MIMBb75 may partially depend on its ability to at least transiently colonize the
      intestine and impact on the resident microbial communities at various intestinal
      loci.

PMID- 23551063
TI  - A high throughput assay for the glucuronidation of 7-hydroxy-4
      trifluoromethylcoumarin by recombinant human UDP-glucuronosyltransferases and
      liver microsomes.
AB  - 1. UDP-glucuronosyltransferases (UGTs) are versatile and important conjugation
      enzymes in the metabolism of drugs and other xenobiotics. 2. We have developed a
      convenient quantitative multi-well plate assay to measure the glucuronidation
      rate of 7-hydroxy-4-trifluoromethylcoumarin (HFC) for several UGTs. 3. We have
      used this method to screen 11 recombinant human UGTs for HFC glucuronidation
      activity and studied the reaction kinetics with the most active enzymes. We have
      also examined the HFC glucuronidation activity of liver microsomes from human,
      pig, rabbit and rat. 4.  At a substrate concentration of 20 uM, the most active
      HFC glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1,
      whereas at 300 uM UGT1A6 was about 10 times better catalyst than the other
      recombinant UGTs. The activities of UGTs 1A3, 1A8, 1A9, 2B4 and 2B7 were low,
      whereas UGT1A1 and UGT2B17 exhibited no HFC glucuronidation activity. UGT1A6
      exhibited a significantly higher Vmax and Km values toward both HFC and UDP
      glucuronic acid than the other UGTs. 5. Human, pig and rabbit, but not rat liver
      microsomes, catalyzed HFC glucuronidation at high rates. 6. This new method is
      particularly suitable for fast activity screenings of UGTs 1A6, 1A7, 1A10 and 2A1
      and HFC glucuronidation activity determination from various samples.

PMID- 23551064
TI  - Prospective, non-interventional study on the tolerability and analgesic
      effectiveness over 12 weeks after a single application of capsaicin 8% cutaneous
      patch in 1044 patients with peripheral neuropathic pain: first results of the
      QUEPP study.
AB  - BACKGROUND: Reversible defunctionalisation of nociceptors by the TRPV1 agonist
      capsaicin in high concentration is an emerging new concept for the treatment of
      peripheral neuropathic pain. OBJECTIVES: The capsaicin 8% cutaneous patch with a
      long-lasting effect for up to 3 months after a single application is available in
      Germany by prescription since October 2010. The aim of this study was to monitor
      its usage and therapeutic performance in clinical practice. METHODS: Patients had
      a single patch application with up to 4 patches and were followed up after 7-14
      days, 4, 8, and 12 weeks. Average pain intensity (NPRS-11), pain attacks,
      neuropathy symptoms, sleep parameters, quality of life, working capacity and
      concomitant neuropathic pain medication were assessed during at least two visits.
      RESULTS: A total of 509 females (48.8%; effectiveness population N = 1044) and
      531 males (50.9%) were included; the mean age was 61.2 +/- 14.4 (SD) years.
      Postherpetic neuralgia was the most frequent diagnosis (31.9%), followed by
      postsurgical neuralgia (22.8%), post-traumatic neuropathy (12.4%), polyneuropathy
      (14.3%), and mixed pain syndromes (16.6%). Thirty and 50% responder rates were
      42.7% and 23.7%, respectively, with a mean relative reduction of pain intensity
      during weeks 1-12 of 24.7% (1.1 SEM) and significant improvements in pain
      attacks, sleep duration and sleep quality, while the consumption of opioids and
      antiepileptics decreased significantly. In 106 patients (10.0%; safety population
      n = 1063) 146 adverse drug reactions (ADRs) were reported, mainly application
      site reactions (erythema, pain). A total of 27 serious ADRs were documented in 17
      patients (1.6%). CONCLUSIONS: Analgesic treatment of peripheral neuropathic pain
      with the capsaicin 8% cutaneous patch is safe and effective. LIMITATIONS: The
      study did not include a control group; therefore, a comparison of the results
      with that of therapeutic alternatives is not justified.

PMID- 23551065
TI  - Relationship between background cancer pain, breakthrough pain, and analgesic
      treatment: a preliminary study for a better interpretation of epidemiological and
      clinical studies.
AB  - BACKGROUND: The different operational definitions of breakthrough cancer pain
      (BTcP) has generated unclear epidemiological data. METHODS: A consecutive sample
      of patients was categorized on the basis of their background pain intensity,
      background analgesic treatment, and the presence of BTcP. RESULTS: A total of 265
      patients were surveyed; 117 patients had background pain and 91 patients
      presented peaks of pain intensity distinguishable from background pain. Of 117
      patients with background pain, 49 patients were re-assessed after optimization of
      background analgesia (T1) within a mean of 8.2 days. Pain intensity significantly
      decreased in comparison with values recorded at admission (p < 0.0005); 75.5% of
      these patients had BTcP episodes, with a significant decrease in the number BTcP
      episodes in comparison with T0 (p < 0.0005). The mean BTcP intensity was
      significantly lower in comparison with T0 (p < 0.0005). Finally, the mean
      duration of untreated BTcP episodes decreased significantly in comparison with T0
      (p = 0.016). After optimization of analgesic therapy, most patients with moderate
      or severe background pain receiving opioids for moderate pain, patients with
      moderate or severe pain receiving strong opioids, and patients with moderate or
      severe pain receiving no opioids moved to the group of patients with mild pain
      receiving strong opioids. The difference was significant (p = 0.022). CONCLUSION:
      Patients having good pain control after optimization of the analgesic regimen may
      have a decrease in number, intensity, and duration of BTcP, although the general
      prevalence of BTcP remains unchanged.

PMID- 23551066
TI  - An approach for optimal allocation of safety resources: using the knapsack
      problem to take aggregated cost-efficient preventive measures.
AB  - On the basis of the combination of the well-known knapsack problem and a widely
      used risk management technique in organizations (that is, the risk matrix), an
      approach was developed to carry out a cost-benefits analysis to efficiently take
      prevention investment decisions. Using the knapsack problem as a model and
      combining it with a well-known technique to solve this problem, bundles of
      prevention measures are prioritized based on their costs and benefits within a
      predefined prevention budget. Those bundles showing the highest efficiencies, and
      within a given budget, are identified from a wide variety of possible
      alternatives. Hence, the approach allows for an optimal allocation of safety
      resources, does not require any highly specialized information, and can therefore
      easily be applied by any organization using the risk matrix as a risk ranking
      tool. 

PMID- 23551067
TI  - Is there evidence for clinical differences related to the new classification of
      temporal lobe cortical dysplasia?
AB  - PURPOSE: The new International League Against Epilepsy (ILAE) classification for
      focal cortical dysplasia (FCD) differentiates between patients with isolated FCD
      (type 1) and FCD with an associated hippocampal sclerosis (HS) (type 3a). In
      contrast to the former FCD classification by Palmini, which considered only
      histologic features, the novel ILAE classification also relies on magnetic
      resonance imaging (MRI) findings and presumed pathogenesis. We investigated in a
      cohort of 100 patients with exclusively temporal FCD if the new subdivision of
      FCD is reflected in clinical characteristics. METHODS: Thirty-one patients with
      FCD type 1 and 50 patients with FCD type 3a in the temporal lobe were included.
      In all patients MRI and histology of the FCD were available. Both patient groups
      were compared to 19 patients with temporal FCD type 2 with clearly different
      histologic appearance. KEY FINDINGS: Patients with FCD type 1 and type 3a
      presented with similar clinical features in many respects. In univariate
      analyses, no statistically significant differences were found as to age at
      epilepsy onset (p = 0.07) and epilepsy surgery (p = 0.14), a normal appearing
      neocortical temporal lobe (p = 0.08) or diagnosis of FCD by visual inspection of
      MRI (p = 0.08), preoperative seizure frequency (p = 0.06), and the predominance
      of an epigastric aura (p = 0.08). The postoperative outcome was nearly identical
      1 year (p = 0.8) and 2 (p = 0.8), 3 (p = 0.8), 5 (p = 0.7), and 8 (p = 1.0) years
      postoperatively. Only febrile seizures (p = 0.025) and an aura (p = 0.03) were
      significantly more frequently reported in patients with FCD type 3a. Similar
      results were obtained from a multivariate logistic regression analysis. Patients
      with FCD type 2 were more different: Compared to FCD type 3a, age at epilepsy
      surgery was significantly lower (p = 0.004) and auras (p = 0.005) were
      significantly less frequently reported. Epigastric auras (p = 0.04) and febrile
      seizures (p = 0.025) occurred significantly less frequently in patients with FCD
      type 2 without HS compared to FCD type 3a. The diagnosis of an FCD was
      significantly more frequently made (p = 0.03) by visual inspection of the MRI
      compared to FCD type 1. SIGNIFICANCE: Clinical features did not allow to clear
      separation of temporal FCD types 1 and 3a. Statistically significant differences
      were seen in a history of febrile seizures and the occurrence of auras more
      common in FCD type 3a. However, FCD type 2 in the same localization but with
      different histology presented with further differences such as more frequent FCD
      diagnosis by visual inspection of MRI, earlier operation, and less frequent
      epigastric auras.

PMID- 23551069
TI  - Antioxidant status and oxidative stress in patients with chronic ITP.
AB  - The aim of this study was to establish the antioxidant status and oxidative
      stress in adult patients with chronic idiopathic thrombocytopenic purpura (ITP).
      Eighty-four patients diagnosed with chronic ITP were studied. Fifty-eight age
      matched healthy subjects were selected as controls. Serum nitrogen monoxide (
      NO), oxidized glutathione (GSSG), malondialdehyde (MDA), total antioxidant status
      (TAS), total oxidant status (TOS), superoxide dismutase(SOD), hydrogen peroxide
      enzyme (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH) were evaluated
      by enzyme-linked immunosorbent assay (ELISA). It was found that serum SOD, CAT,
      GSH-Px, GSH, TAS levels were significantly lower in patients with chronic ITP
      than controls (all P < 0.05), while serum NO, GSSG, MDA, TOS values were
      significantly higher (P < 0.05). The number of platelet showed a negative
      correlation with NO, GSSG, MDA, TOS, respectively,while platelet number showed a
      positive correlation with SOD, CAT, GSH-Px, GSH, TAS. These findings suggested
      that oxidants were increased and antioxidants were decreased in patients with
      chronic ITP, these may be prominent factors in destructing the platelet membrane.
      The scavenging of oxygen radical provides a theoretical basis for the treatment
      of ITP patients.

PMID- 23551071
TI  - Pelvic floor muscle training improves quality of life of women with urinary
      incontinence: a prospective study.
AB  - BACKGROUND: Women suffering from urinary incontinence have impaired quality of
      life (QoL). Pelvic floor muscle training (PFMT) has been recommended to be the
      first-line treatment for them. AIMS: This study evaluated the role of (PFMT) in
      women with urinary incontinence. MATERIALS AND METHODS: All women suffering from
      urinary incontinence without pelvic organ prolapse who attended the
      urogynaecology unit of a university hospital from January 2009 to June 2010 were
      recruited. Urinary symptoms and impact on QoL were assessed using the Chinese
      validated Urogenital Distress Inventory short form (UDI-6) and Incontinence
      Impact Questionnaire short form (IIQ-7) before and after PFMT. Urodynamic studies
      (UDS) were used to differentiate the diagnoses of urinary incontinence. RESULTS:
      Three hundred and seventy-two women, aged 52.3 +/- 10.8 years and practised PFMT
      for 9.9 +/- 7.3 months, completed the study. Over 65% recorded improvement in
      both UDI-6 and IIQ-7. Stratified for urodynamic diagnosis, stress incontinence
      group and those who had no UDS abnormality had significant improvement in their
      urinary symptoms and QoL after PFMT. UDI-6 and IIQ-7 also improved significantly
      after PFMT in groups where the clinical presentation was stress incontinence,
      overactive bladder symptoms or mixed urinary incontinence. Age was not associated
      with a significant difference in the response to PFMT. CONCLUSIONS: Pelvic floor
      muscle training appears to be an effective first-line intervention for improving
      urinary symptoms and QoL of women presenting with urinary incontinence. Future
      studies on long-term effectiveness and cost-effectiveness are also required.

PMID- 23551070
TI  - Effects of intranasal oxytocin on pupil dilation indicate increased salience of
      socioaffective stimuli.
AB  - To investigate the mechanisms by which oxytocin improves socioaffective
      processing, we measured behavioral and pupillometric data during a dynamic facial
      emotion recognition task. In a double-blind between-subjects design, 47 men
      received either 24 IU intranasal oxytocin (OXT) or a placebo (PLC). Participants
      in the OXT group recognized all facial expressions at lower intensity levels than
      did participants in the PLC group. Improved performance was accompanied by
      increased task-related pupil dilation, indicating an increased recruitment of
      attentional resources. We also found increased pupil dilation during the
      processing of female compared with male faces. This gender-specific stimulus
      effect diminished in the OXT group, in which pupil size specifically increased
      for male faces. Results suggest that improved emotion recognition after OXT
      treatment might be due to an intensified processing of stimuli that usually do
      not recruit much attention.

PMID- 23551072
TI  - Expecting the unexpected: predicting physiological and psychological wildfire
      preparedness from perceived risk, responsibility, and obstacles.
AB  - People who live in wildfire-prone communities tend to form their own hazard
      related expectations, which may influence their willingness to prepare for a
      fire. Past research has already identified two important expectancy-based factors
      associated with people's intentions to prepare for a natural hazard: Perceived
      risk (i.e., perceived threat likelihood and severity) and perceived protection
      responsibility. We expanded this research by differentiating the influence of
      these factors on different types of wildfire preparedness (e.g., preparations for
      evacuation vs. for defending the house) and measured actual rather than intended
      preparedness. In addition, we tested the relation between preparedness and two
      additional threat-related expectations: the expectation that one can rely on an
      official warning and the expectation of encountering obstacles (e.g., the loss of
      utilities) during a fire. A survey completed by 1,003 residents of wildfire-prone
      areas in Perth, Australia, revealed that perceived risk (especially risk
      severity) and perceived protection responsibility were both positively associated
      with all types of preparedness, but the latter did not significantly predict
      preparedness after controlling for other predictors and demographics. Also, the
      two new expectancy-based factors were significantly associated with all types of
      preparedness, and remained significant predictors of some types of preparedness
      after controlling for other predictors and demographics: the expectation of being
      able to rely on an official fire warning and expecting to lose electricity both
      still predicted less preparedness around house resilience, and expecting to lose
      water still predicted increased planning preparedness. We discuss public policy
      implications that follow from this research. 

PMID- 23551073
TI  - Comparison of nasalance scores obtained with the nasometers 6200 and 6450.
AB  - OBJECTIVE: The study had the goal of comparing the new Nasometer 6450 to the
      older model 6200 using synthetic test sounds and control participants. A
      particular focus of the investigation was on the test-retest variability of the
      instruments. MATERIALS AND METHODS: The Nasometers 6200 and 6450 were compared
      using square wave test sounds. Six repeated measurements of oral, balanced, and
      nasal test stimuli were recorded from 25 female participants over an average of
      35 days. RESULTS: The synthetic test sounds demonstrated that the two nasometers
      obtained similar results for a range of frequencies. The results for the
      clinically normal participants revealed that nasalance scores from the two
      instruments were within 1-2 points, depending on the test sentence. Variability
      in scores increased with the proportion of nasal consonants in the sentence. Test
      retest variability was between 6 and 8 points for more than 90% of the
      participants. Participants with higher nasalance scores for oral stimuli had
      higher between-session variability. CONCLUSIONS: The Nasometers 6200 and 6450
      should yield comparable results in clinical practice. Depending on the phonetic
      content of the test materials, clinicians should allow for a 6- to 8-point
      between-session variability when interpreting nasalance scores.

PMID- 23551074
TI  - Harvey Cushing's Contributions to Plastic Surgery: Bilateral Cleft Lip Repair.
AB  - Harvey Cushing has been deemed by many as the neurosurgeon of the 20th century.
      Cushing's unknown contributions to the field of plastic and reconstructive
      surgery were only recently reported. Further review of his teaching and operative
      records, brought from Johns Hopkins to Yale University, revealed an unpublished
      case of bilateral cleft lip repair that he performed. In this article, we present
      in detail this comprehensive case and describe, with the help of his personal
      teaching notes and illustrations, how Cushing combined methods from world
      renowned surgeons to approach bilateral cleft lip deformities. 

PMID- 23551075
TI  - Feeding Infants With Cleft Lip and/or Palate in Brazil: Suggestions to Improve
      Health Policy and Research.
AB  - Objective : To verify feeding resources used prior to corrective surgery among
      cleft babies from Brazil and to discuss suggestions to improve common feeding
      problems around the world. Design : Cross-sectional descriptive study conducted
      at eight medical centers. Participants : A total of 215 parents or guardians of
      cleft children. Methods : Interview based upon a prevalidated questionnaire. The
      chi-square test and comparison of means by analysis of variance were used;
      significance level adopted was 5% (P < .05). Results : Feeding guidelines were
      provided in the maternity unit to 53% of the families. Breast-feeding was
      encouraged among 80% of mothers, predominantly in the South (P = .016). However,
      follow-up after maternity discharge was not appropriately carried out and failure
      to breast-feed occurred in 78% of families. The feeding tube was used in 21%.
      According to families, for those who used the ordinary nipple, it was considered
      the best option by the majority (29%). Conclusion : Neonatal feeding in cleft
      babies is a global challenge. Reports about the difficulties encountered and
      successful experiences would be helpful to disseminate strategies and stimulate
      research directed at the large-scale applicability of neonatal feeding for cleft
      babies on public health. This study detected the need to increase professional
      training and emphasizes the need for public policies addressing neonatal referral
      to specialized care wherever possible. It also stimulates research into using an
      ordinary nipple as another resource for feeding cleft babies and suggests an
      international discussion about specific recommendations for humanized primary
      health care. 

PMID- 23551076
TI  - Incidence of cleft lip and palate in the palestinian territories: a retrospective
      study from the Makassed Hospital neonatal unit.
AB  - BACKGROUND: Cleft lip, with or without cleft palate (CL+/-P), is the most common
      craniofacial anomaly in newborns. The incidence of CL+/-P varies among different
      ethnic populations and is presumed to be higher in developing countries. In the
      Middle East, the incidence has variably been reported as 0.3 to 2.19 per 1000
      live births and is generally regarded as similar to Caucasians. There is
      currently no literature reporting the incidence of clefting in Palestinians
      living in the territories. Reports from Palestinian populations in Israel and
      Jordan infer an incidence of 1.39 per 1000 live births. However, the reported
      incidence in stable populations may not reflect the actual incidence of clefting
      in the territories. METHODS: This is a retrospective study examining all newborn
      records at Makassed Maternity Hospital in Jerusalem between January 1, 1986, and
      December 12, 1995. Data were collected by the senior author (A.D.) and
      interpreted by coauthors. Frequencies were established based on the number of
      isolated and nonisolated CL+/-P born during this time period. RESULTS: During the
      10-year period from January 1, 1986, to December 12, 1995, there were 33,239 live
      births. Among these births, there were 35 isolated and nonisolated combined CL+/
      P born (1.05/1000 live births). CONCLUSIONS: Based on this limited data set from
      a single, tertiary referral hospital, we conclude that the prevalence rate of
      CL+/-P among a Palestinian population may be less than that reported in
      surrounding areas. However, more broadly based studies using nationalized birth
      registries are required to determine an accurate prevalence rate of CL+/-P among
      Palestinians.

PMID- 23551077
TI  - Co-cultivation of Sorangium cellulosum strains affects cellular growth and
      biosynthesis of secondary metabolite epothilones.
AB  - Sorangium cellulosum, a cellulolytic myxobacterium, is capable of producing a
      variety of bioactive secondary metabolites. Epothilones are anti-eukaryotic
      secondary metabolites produced by some S. cellulosum strains. In this study, we
      analyzed interactions between 12 strains of S. cellulosum consisting of
      epothilone-producers and non-epothilone producers isolated from two distinct soil
      habitats. Co-cultivation on filter papers showed that different Sorangium strains
      inhibited one another's growth, whereas epothilone production by the producing
      strains changed markedly for most (73%) pairwise mixtures. Using a quantitative
      polymerase chain reaction, we demonstrated that the expression of epothilone
      biosynthetic genes in the epothilone producers typically changed significantly
      when these bacteria were mixed with non-producing strains. The results indicated
      that intraspecies interactions between different S. cellulosum strains not only
      inhibited the growth of partners, but also could change epothilone production. 

PMID- 23551078
TI  - Concrete behaviour and reappraisal deficits after a left frontal stroke: a case
      study.
AB  - Concrete behaviour, the inability to disengage from immediate experience in order
      to manipulate ideas and thoughts, has long been understood to be a common problem
      after frontal lobe lesions. However, there has been little consideration of the
      impact that concreteness may have on emotional functioning, specifically in the
      use of thinking to manipulate emotional responses. One widely studied emotion
      regulation strategy is reappraisal, which depends on several frontal lobe related
      cognitive control processes. While there have been numerous neuroimaging findings
      on reappraisal, no study has used brain injured patients to investigate this
      issue. The present case study is the first to describe the capacity to generate
      reappraisals in a patient (Mrs M), whose behaviour became concrete after a left
      prefrontal stroke. Using a picture-based reappraisal paradigm, her performance
      was compared to non-concrete brain-lesioned patients, and neurologically healthy
      controls. Although Mrs M showed relatively preserved overall cognitive function,
      she was completely unable to spontaneously generate reappraisals. In striking
      contrast, once external support was offered, in the form of prompts, her capacity
      to reappraise dramatically improved. The results are analysed in terms of three
      neuropsychological capacities - all compromised in Mrs M - previously proposed as
      reappraisal components: response inhibition, abstraction, and verbal fluency. A
      number of implications for rehabilitation are discussed, including how the use of
      prompting may facilitate reappraisal capacity. 

PMID- 23551079
TI  - A survey of adult and pediatric epilepsy surgery in the United Kingdom.
AB  - All consultant epilepsy neurosurgeons were asked to prospectively record all
      epilepsy surgery procedures carried out at their center between April 2010 and
      March 2011. Figures were compared to a previous survey completed in 2000. Of a
      total of 710 procedures, temporal lobe surgery was the most common resective
      surgery. Although extratemporal lesional surgery was less common, vagus nerve
      stimulator (VNS) implantation accounted for almost half the procedures. The
      numbers for all surgical procedures, with the exception of VNS implantations, had
      decreased. This decrease may represent a global rather than a regional
      phenomenon. Further longitudinal multinational data on epilepsy surgery is
      required to confirm or refute this theory.

PMID- 23551080
TI  - C-reactive protein triggers calcium signalling in human neutrophilic granulocytes
      via FcgammaRIIa in an allele-specific way.
AB  - C-reactive protein (CRP) binds to Fcgamma-receptors, FcgammaRIIa (CD32) with high
      affinity and to FcgammaRIa (CD64) with low affinity. The binding to CD32 has been
      shown to be allele specific, that is, it binds to R/R131 but not to H/H131.
      Little is known about the cooperation of CRP and neutrophilic granulocytes (PMNs)
      in inflammatory reactions. The purpose of the present study was to examine CRP
      signalling in human PMNs, and whether this signalling is also allele specific.
      Cytosolic calcium of PMN was measured in a single-cell digital imaging system.
      Receptor expression and polymorphism were studied by real-time RT-PCR, flow
      cytometry and standard PCR. C-reactive protein induced cytosolic calcium signals
      in PMNs from homozygote R/R131 donors, but not in PMNs from heterozygote R/H131
      donors. However, after the heterozygote PMNs had been incubated with IFN-gamma
      (100 U/ml) for 2 h, both the proportion of cells responding and the size of the
      CRP-induced calcium signals increased. IFN-gamma increased mRNA expression of
      CD64 about fivefold and surface protein expression of CD64 about fourfold. The
      calcium signal elicited by CRP was augmented by PMN adhesion to fibronectin, but
      almost totally abrogated by sphingosine kinase inhibitors. The signals were
      partly dependent on calcium influx. In conclusion, calcium signalling instigated
      by CRP in human PMN is FcgammaRIIa allele specific, as R/R131 responded to CRP,
      whereas R/H131 did not. However, increased expression of FcgammaRIa (CD64),
      stimulated by IFN-gamma, can augment calcium signalling by CRP in low-responders.
      This suggests that the state of the PMNs, as well as the genetic origin, affect
      sensitivity for CRP.

PMID- 23551081
TI  - Exome sequencing reveals a novel ANO10 mutation in a Japanese patient with
      autosomal recessive spinocerebellar ataxia.

PMID- 23551082
TI  - Peak individual alpha frequency qualifies as a stable neurophysiological trait
      marker in healthy younger and older adults.
AB  - The individual alpha frequency (IAF) of the human EEG reflects systemic
      properties of the brain, is highly heritable, and relates to cognitive
      functioning. Not much is known about the modifiability of IAF by cognitive
      interventions. We report analyses of resting EEG from a large-scale training
      study in which healthy younger (20-31 years, N = 30) and older (65-80 years, N =
      28) adults practiced 12 cognitive tasks for ~100 1-h sessions. EEG was recorded
      before and after the cognitive training intervention. In both age groups, IAF
      (and, in a control analysis, alpha amplitude) did not change, despite large gains
      in cognitive performance. As within-session reliability and test-retest stability
      were high for both age groups, imprecise measurements cannot account for the
      findings. In sum, IAF is highly stable in healthy adults up to 80 years, not
      easily modifiable by cognitive interventions alone, and thus qualifies as a
      stable neurophysiological trait marker.

PMID- 23551083
TI  - Evaluating methods for estimating existential risks.
AB  - Researchers and commissions contend that the risk of human extinction is high,
      but none of these estimates have been based upon a rigorous methodology suitable
      for estimating existential risks. This article evaluates several methods that
      could be used to estimate the probability of human extinction. Traditional
      methods evaluated include: simple elicitation; whole evidence Bayesian;
      evidential reasoning using imprecise probabilities; and Bayesian networks. Three
      innovative methods are also considered: influence modeling based on environmental
      scans; simple elicitation using extinction scenarios as anchors; and
      computationally intensive possible-worlds modeling. Evaluation criteria include:
      level of effort required by the probability assessors; level of effort needed to
      implement the method; ability of each method to model the human extinction event;
      ability to incorporate scientific estimates of contributory events; transparency
      of the inputs and outputs; acceptability to the academic community (e.g., with
      respect to intellectual soundness, familiarity, verisimilitude); credibility and
      utility of the outputs of the method to the policy community; difficulty of
      communicating the method's processes and outputs to nonexperts; and accuracy in
      other contexts. The article concludes by recommending that researchers assess the
      risks of human extinction by combining these methods. 

PMID- 23551084
TI  - Corona mortis: anatomical data and clinical considerations.
AB  - BACKGROUND: Minimally invasive procedures, such as the TVT-SecurTM, have been
      linked to injury to the corona mortis. Injury during the insertion of the TVT
      SecurTM happens due to the vessel's position close to the place of the margin (25
      30 mm from the symphysis pubis). AIMS: Systematic description of the aberrant
      vessel anatomy so as to help gynaecologists determine the risk of peri- and
      postoperative complications during the TVT-SecurTM and related procedures.
      METHODS: In a cadaver study, the lesser pelvis of ten female cadavers with venous
      or arterial coronae mortis was dissected. The origin, diameter and course of the
      aberrant vessels, as well as the distance from the symphysis pubis, were
      documented. RESULTS: Arterial coronae mortis were found in eight hemipelvises.
      All vessels originated from the ipsilateral inferior epigastric artery and all
      crossed over the superior pubic rami. Average distance from the symphysis pubis
      was 52.4 mm. Average vessel diameter was 3 mm. Venous coronae mortis were
      identified in ten hemipelvises. Eight drained into the external iliac and four
      into the inferior epigastric artery. Nine vessels crossed over the superior pubic
      rami. Average distance from the symphysis pubis was 46.7 mm. Average vessel
      diameter was 3.13 mm. CONCLUSION: Although individual variation makes direct
      contact with the vessel possible, in most cases there is a window of eight
      millimetres at least between the margin of the TVT-SecurTM and most aberrant
      veins. Possible aberrant arteries seem to lie even further.

PMID- 23551088
TI  - Patterns of cortical hyperexcitability in adolescent/adult-onset generalized
      epilepsies.
AB  - PURPOSE: To investigate whether using transcranial magnetic stimulation (TMS) to
      derive if measures of cortical excitability changes can distinguish between
      various adolescent/adult-onset generalized epilepsy syndromes at different phases
      of the disorder. METHODS: One hundred thirty-seven patients with adolescent/adult
      onset generalized epilepsy divided into juvenile myoclonic epilepsy, juvenile
      absence epilepsy, and generalized epilepsy with tonic-clonic seizures only were
      studied. The cohorts were further divided into drug naive-new onset, refractory,
      and seizure-free groups. Motor threshold (MT) and paired pulse TMS at short (2,
      5, 10, 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were
      measured. Results were compared to those of 20 controls. KEY FINDINGS: In the
      drug-naive cohorts MT was reduced (p < 0.05) and cortical excitability increased
      at 2 and 5 msec and 150, 250, and 300 msec ISIs (p < 0.01) in juvenile myoclonic
      epilepsy compared to other generalized epilepsy groups and controls. Cortical
      excitability increased to a lesser degree in other generalized epilepsy syndromes
      compared to controls, but those two syndromes were not distinguishable from one
      another. The changes in paired pulse TMS were more prominent in the groups with
      refractory seizures and very small in the groups who were seizure free.
      SIGNIFICANCE: There are syndrome specific changes in cortical excitability
      associated with generalized epilepsy. These changes are also dependent on seizure
      control with medication. Juvenile myoclonic epilepsy has a higher cortical
      excitability profile compared to other adolescent/adult-onset generalized
      epilepsy syndromes and can be clearly distinguished from them during all phases.

PMID- 23551085
TI  - Long-term robust myocardial transduction of the dog heart from a peripheral vein
      by adeno-associated virus serotype-8.
AB  - Molecular intervention using noninvasive myocardial gene transfer holds great
      promise for treating heart diseases. Robust cardiac transduction from peripheral
      vein injection has been achieved in rodents using adeno-associated virus (AAV)
      serotype-9 (AAV-9). However, a similar approach has failed to transduce the heart
      in dogs, a commonly used large animal model for heart diseases. To develop an
      effective noninvasive method to deliver exogenous genes to the dog heart, we
      employed an AAV-8 vector that expresses human placental alkaline phosphatase
      reporter gene under the transcriptional regulation of the Rous sarcoma virus
      promoter. Vectors were delivered to three neonatal dogs at the doses of
      1.35*10(14), 7.14*10(14), and 9.06*10(14) viral genome particles/kg body weight
      via the jugular vein. Transduction efficiency and overall safety were evaluated
      at 1.5, 2.5, and 12 months postinjection. AAV delivery was well tolerated and dog
      growth was normal. Blood chemistry and internal organ histology were
      unremarkable. Widespread skeletal muscle transduction was observed in all dogs
      without T-cell infiltration. Encouragingly, whole heart myocardial transduction
      was achieved in two dogs that received higher doses and cardiac expression lasted
      for at least 1 year. In summary, peripheral vein AAV-8 injection may represent a
      simple heart gene transfer method in large mammals. Further optimization of this
      gene delivery strategy may open the door for a readily applicable gene therapy
      method to treat many heart diseases.

PMID- 23551089
TI  - Development of a new chewing function questionnaire for assessment of a self
      perceived chewing function.
AB  - OBJECTIVE: To develop a new unidimensional questionnaire for patients' self
      assessment of their chewing function (chewing function questionnaire: CFQ) and to
      test its psychometric properties. METHODS: A focus group of 7 dentists and 15
      prosthodontic patients generated a pool of 30 relevant items. A 5-point Likert
      scale (0-4) was used. A focus group reduced some redundant items, and 21 items
      remained for pilot testing after which additional four items were eliminated.
      Then, the 17-item questionnaire was tested on a larger sample (200 participants).
      Factor analysis was obtained to investigate the dimensionality of the
      questionnaire. Finally the 10 items remained, and the CFQ was unidimensional. To
      test the psychometric properties, the CFQ was administrated to 224 individuals:
      100 patients were already removable denture wearers (RDWs), 24 patients needed a
      removable prosthodontic treatment, and 100 individuals had natural teeth (NT
      group). Discriminative validity was tested between the RDWs and the NT groups.
      Convergent validity and internal consistency were tested on 200 subjects. The
      internal consistency was assessed by calculating the Cronbach's alpha coefficient
      and the average interitem correlation. The test-retest reliability was tested on
      60 subjects. Responsiveness was tested on 24 patients who received new removable
      prosthodontic treatment. RESULTS: The initial factor analysis revealed that the
      items had been grouped in three different dimensions. By eliminating items with
      complexities greater than one, additional six questions were eliminated. One more
      item with the lowest correlation was further eliminated. The final questionnaire
      included 10 items. Discriminative validity showed significant differences between
      the NT group and the RDWs, as predicted (P < 0.001). Convergent validity was
      confirmed by the Spearman's rank correlation. A significant positive association
      (P < 0.001) was found between the CFQ and one general question about chewing
      difficulties, as well as between the CFQ and five items from the OHIP49 related
      to chewing. The test-retest reliability showed high intraclass correlation and no
      significant differences between the two administrations of the CFQ (P > 0.05).
      The internal consistency showed satisfactory Cronbach's alpha values (0.916 for
      all subjects, 0.742 for the NT group, and 0.852 for the RDWs). Responsiveness was
      confirmed by a significant difference between the baseline and the follow-up
      score (P < 0.001) and a high effect size (0.95). CONCLUSIONS: The developed CFQ
      provides an assessment instrument of the hypothetical construct invoked to
      explain the chewing function. Psychometric properties are satisfactory
      demonstrating that the instrument is suitable for the assessment of a self
      perceived chewing function.

PMID- 23551090
TI  - Response to letter to the editor regarding "melanotan II injection resulting in
      systemic toxicity and rhabdomyolysis" in Clinical Toxicology 2012; 50(10):1169
      73.

PMID- 23551091
TI  - Risks perception of electromagnetic fields in Taiwan: the influence of
      psychopathology and the degree of sensitivity to electromagnetic fields.
AB  - Little is known about the perceived health risks of electromagnetic fields (EMFs)
      and factors associated with risk perception in non-Western countries.
      Psychological conditions and risk perception have been postulated as factors that
      facilitate the attribution of health complaints to environmental factors. This
      study investigated people's perceived risks of EMFs and other environmental
      sources, as well as the relationships between risk perception, psychopathology,
      and the degree of self-reported sensitivity to EMFs. A total of 1,251 adults
      selected from a nationwide telephone interviewing system database responded to a
      telephone survey about the relationships between environmental sources and human
      health. The interview included questions assessing participants' psychiatric
      conditions and the presence and degree of sensitivity to EMFs. One hundred and
      seventy participants were self-identified as having sensitivity to EMFs, and 141
      met the criteria for psychiatric conditions without EMF sensitivity. More than
      half of the survey respondents considered power lines and mobile phone base
      stations to affect people's health to a big extent. Higher sensitivity to EMFs,
      psychopathology, being female, being married, more years of education, and having
      a catastrophic illness had positive associations with perceived risks of EMF
      related environmental sources as well as for all environmental sources combined.
      We observed no moderating effect of psychopathology on the association between
      degree of sensitivity to EMF and risk perception. Thus, psychopathology had
      influence on general people's risk perception without having influence on the
      relationship between people's degree of sensitivity to EMF and risk perception.
      The plausible explanations are discussed in the text. 

PMID- 23551092
TI  - Molecular and clinical characterization of Angelman syndrome in Chinese patients.
AB  - Angelman syndrome (AS) is a neurobehavioral disorder caused by lack of function
      of the maternal copy of the ubiquitin-protein ligase E3A (UBE3A) gene. In our
      study, 49 unrelated patients with classic AS phenotypes were confirmed by
      methylation-specific PCR (MS-PCR) analysis, short tandem repeat linkage analysis,
      and mutation screening of the UBE3A gene. Among the Chinese AS patients, 83.7%
      (41/49) had deletions on maternal chromosome 15q11.2-13. Paternal uniparental
      disomy, imprinting defects, and UBE3A gene mutations each accounted for 4.1%
      (2/49). Two AS patients were confirmed by MS-PCR analysis, but the pathogenic
      mechanism was unknown because their parents' samples were unavailable. Of the two
      described UBE3A gene mutations, that is, p.Pro400His (c.1199C>A) and p.Asp563Gly
      (c.1688A>G), the latter has not been reported previously. Mutation transmission
      analysis showed that the p.Pro400His and p.Asp563Gly mutations originated from
      asymptomatic mothers. The patients with the maternal deletion showed AS clinical
      manifestations that were consistent with other studies. However, the incidence of
      microcephaly (36.7%, 11/30) was lower than that in the Caucasian population
      (approximately 80%), but similar to that of the Japanese population (34.5%). Our
      study demonstrated that the occurrence of microcephaly in AS may vary among
      different populations. 

PMID- 23551093
TI  - Phosphoinositide 3-kinase and INPP4B in human breast cancer.
AB  - The PI3K/Akt signaling pathway is frequently increased in many human cancers,
      including breast cancer. Recent studies have identified INPP4B, which inhibits
      PI3K signaling, as an emerging tumor suppressor in breast cancer. This short
      review discusses these issues and the possibility that INPP4B is an important
      regulator in many cancers.

PMID- 23551094
TI  - Role of SHIP1 in cancer and mucosal inflammation.
AB  - The SH-2 containing inositol 5'-polyphosphatase 1 (SHIP1) is a multifunctional
      protein expressed predominantly, but not exclusively, by hematopoietic cells.
      SHIP1 removes the 5'-phosphate from the product of PI3K, PI(3,4,5)P3, to generate
      PI(3,4)P2. Both PIP species influence the activity level of Akt and ultimately
      regulate cell survival and differentiation. SHIP1 also harbors several protein
      interaction domains that endow it with many nonenzymatic cell signaling or
      receptor masking functions. In this review, we discuss the opposing roles of
      SHIP1 in cancer and in mucosal inflammation. On one hand, germline loss of SHIP1
      causes myeloid lung consolidation and severe inflammation in the ileum, a
      phenotype that closely mimics human Crohn's disease and can be rescued by
      reconstitution with SHIP1-competent T cells. On the other, transient inhibition
      of the enzymatic activity of SHIP1 in cancer cells leads to apoptosis and
      enhances survival in lethal murine xenograft models. Overall, careful dissection
      of the different pathological mechanisms involved in several diseases provides
      novel opportunities for therapeutic intervention targeting SHIP1.

PMID- 23551095
TI  - Role of SHIP1 in bone biology.
AB  - The bone marrow milieu comprising both hematopoietic and nonhematopoietic
      lineages has a unique structural organization. Bone undergoes continuous
      remodeling throughout life. This dynamic process involves a balance between bone
      forming osteoblasts (OBs) derived from multipotent mesenchymal stem cells (MSCs)
      and bone-resorbing osteoclasts (OCs) derived from hematopoietic stem cells
      (HSCs). Src homology 2-domain-containing inositol 5'-phosphatase 1 (SHIP1)
      regulates cellular processes such as proliferation, differentiation, and survival
      via the PI3K/Akt signaling pathway initiated at the plasma membrane. SHIP1
      deficient mice also exhibit profound osteoporosis that has been proposed to
      result from hyperresorptive activity by OCs. We have previously observed that
      SHIP1 is expressed in primary OBs, which display defective development in SHIP1
      deficient mice. These findings led us to question whether SHIP1 plays a
      functional role in osteolineage development from MSC in vivo, which contributes
      to the osteoporotic phenotype in germline SHIP1 knockout mice. In this short
      review, we discuss our current understanding of inositol phospholipid signaling
      downstream of SHIP1 in bone biology.

PMID- 23551096
TI  - Achieving cancer cell death with PI3K/mTOR-targeted therapies.
AB  - Inhibitors of the PI3K/mTOR signaling network are under development as novel
      cancer therapies. However, these compounds do not cause robust cytotoxic
      responses in tumor cells unless combined with other agents. Rational combinations
      with other targeted therapies will likely be necessary to achieve the potential
      of PI3K/mTOR inhibitors in oncology.

PMID- 23551097
TI  - Challenges in the clinical development of PI3K inhibitors.
AB  - The PI3K/Akt/mTOR pathway is one of the most frequently dysregulated signaling
      pathways in cancer and an important target for drug development. PI3K signaling
      plays a fundamental role in tumorigenesis, governing cell proliferation,
      survival, motility, and angiogenesis. Activation of the pathway is frequently
      observed in a variety of tumor types and can occur through several mechanisms.
      These mechanisms include (but are not limited to) upregulated signaling via the
      aberrant activation of receptors upstream of PI3K, amplification or gain-of
      function mutations in the PIK3CA gene encoding the p110alpha catalytic subunit of
      PI3K, and inactivation of PTEN through mutation, deletion, or epigenetic
      silencing. PI3K pathway activation may occur as part of primary tumorigenesis, or
      as an adaptive response (via molecular alterations or increased phosphorylation
      of pathway components) that may lead to resistance to anticancer therapies. A
      range of PI3K inhibitors are being investigated for the treatment of different
      types of cancer; broad clinical development plans require a flexible yet well
      structured approach to clinical trial design.

PMID- 23551098
TI  - Rules of engagement: distinct functions for the four class I PI3K catalytic
      isoforms in immunity.
AB  - Mammalian cells can express up to four different class I phosphatidylinositide 3
      kinase (PI3K) isoforms, each of which is engaged by tyrosine kinases or G protein
      coupled receptors (GPCRs) to generate the second messenger signaling molecule
      PtdIns(3,4,5)P3 (PIP3). The p110alpha and p110beta isoforms are relatively widely
      expressed, whereas p110gamma and p110delta are more highly expressed in cells of
      the immune system than in other cell types. Nevertheless, each of the four class
      I PI3Ks have been shown to participate in the orchestration of the signaling
      events that lead to immune cell development and control of gene expression,
      skewing toward individual cell lineage subsets and proliferation.

PMID- 23551099
TI  - Control of T cell tolerance by phosphatase and tensin homolog.
AB  - The in vivo maintenance of immune tolerance is critically dependent on regulatory
      T (Treg ) cells, a lineage of CD4(+) T cells expressing the transcription factor
      Foxp3 that exerts immunoregulatory function. Because of the potential benefit of
      using Treg cells for cellular immunotherapy in clinical settings, including
      autoimmune disease and transplantation, much attention has been directed at
      understanding the signals that govern Treg cell development, function, and
      homeostasis. Studies with genetically modified mouse models have shown that the
      lipid phosphatase PTEN (phosphatase and tensin homolog), the predominant negative
      regulator of the PI3K/Akt pathway in T cells, has multiple functions in
      sustaining T cell-mediated immune tolerance in vivo. In addition to its role in
      maintaining T cell homeostasis, the PI3K/Akt pathway also has an essential role
      in T cell development and lineage commitment, contributing to the cell fate
      decision between conventional and regulatory T cells.

PMID- 23551100
TI  - Role of PI3K/Akt and mTOR complexes in Th17 cell differentiation.
AB  - Interleukin (IL)-17-producing helper T (Th17) cells serve as a Th subset involved
      in epithelial cell- and neutrophil-mediated immune responses against
      extracellular microbes and in the development of various autoimmune diseases. The
      differentiation of Th17 cells is controlled by a number of intracellular
      signaling cascades and a complex network of transcription factors. Recently, it
      has been shown that PI3K, Akt, and mammalian target of rapamycin (mTOR)
      complexes, such as mTORC1 and mTORC2, also positively regulate Th17
      differentiation both in vivo and in vitro via multiple mechanisms; here, we
      review the current knowledge regarding the mechanisms through which these
      molecules enhance Th17 differentiation.

PMID- 23551102
TI  - Phosphoinositide 3-kinase gamma in T cell biology and disease therapy.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) kinase activity is important for its
      signaling functions in T cell development, activation, differentiation, and
      trafficking. Protection of PI3Kgamma knockout mice from disease in multiple
      autoimmune models suggests that targeting PI3Kgamma alone, or in combination with
      PI3Kdelta, could be a promising approach to disease therapy.

PMID- 23551101
TI  - Targeting phosphoinositide 3-kinase delta for the treatment of respiratory
      diseases.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are characterized in
      their pathogenesis by chronic inflammation in the airways. Phosphoinositide 3
      kinase delta (PI3Kdelta), a lipid kinase expressed predominantly in leukocytes,
      is thought to hold much promise as a therapeutic target for such inflammatory
      conditions. Of particular interest for the treatment of severe respiratory
      disease is the observation that inhibition of PI3Kdelta may restore steroid
      effectiveness under conditions of oxidative stress. PI3Kdelta inhibition may also
      prevent recruitment of inflammatory cells, including T lymphocytes and
      neutrophils, as well as the release of proinflammatory mediators, such as
      cytokines, chemokines, reactive oxygen species, and proteolytic enzymes. In
      addition, targeting the PI3Kdelta pathway could reduce the incidence of pathogen
      induced exacerbations by improving macrophage-mediated bacterial clearance. In
      this review, we discuss the potential and highlight the unknowns of targeting
      PI3Kdelta for the treatment of respiratory disease, focusing on recent
      developments in the role of the PI3Kdelta pathway in inflammatory cell types
      believed to be critical to the pathogenesis of COPD.

PMID- 23551103
TI  - Inhibition of phosphoinositide 3-kinase gamma attenuates inflammation, obesity,
      and cardiovascular risk factors.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) plays a central role in inflammation,
      allergy, cardiovascular, and metabolic disease. Obesity is accompanied by
      chronic, low-grade inflammation. As PI3Kgamma plays a major role in leukocyte
      recruitment, targeting of PI3Kgamma has been considered to be a strategy for
      attenuating progression of obesity to insulin resistance and type 2 diabetes.
      Indeed, PI3Kgamma null mice are protected from high fat diet-induced obesity,
      metabolic inflammation, fatty liver, and insulin resistance. The lean phenotype
      of the PI3Kgamma-null mice has been linked to increased thermogenesis and energy
      expenditure. Surprisingly, the increase in fat mass and metabolic aberrations
      were not linked to PI3Kgamma activity in the hematopoietic compartment.
      Thermogenesis and oxygen consumption are modulated by PI3Kgamma lipid kinase
      dependent and -independent signaling mechanisms. PI3Kgamma signaling controls
      metabolic and inflammatory stress, and may provide an entry point for therapeutic
      strategies in metabolic disease, inflammation, and cardiovascular disease.

PMID- 23551104
TI  - Class III PI3K Vps34: essential roles in autophagy, endocytosis, and heart and
      liver function.
AB  - Mammalian phosphatidylinositol (PI) 3-kinases are a family of proteins that share
      the ability to phosphorylate phosphoinositides at the 3 position of the inositol
      ring. By doing so, these kinases produce phospholipid molecules that are involved
      in various cell signaling pathways, such as insulin signaling and endocytosis.
      The pathways regulated by PI3-kinases are crucial for maintaining cellular
      homeostasis and thus must be tightly regulated. Irregular PI3-kinase activity is
      observed in numerous human pathological conditions, such as diabetes, cancer, and
      inflammation. One family member, Vps34, is of particular interest because it is
      the only PI3-kinase identified in yeast and it has been evolutionarily conserved
      through mammals. Vps34 plays an essential role in the cellular process of
      autophagy, a process linked to human health and disease. Understanding the
      precise role of mammalian Vps34 will likely be integral to drug development for
      various diseases.

PMID- 23551105
TI  - Inpp4b is a novel negative modulator of osteoclast differentiation and a
      prognostic locus for human osteoporosis.
AB  - Inositol polyphosphate 4-phosphatase type II (Inpp4b) is a novel negative
      modulator of osteoclast differentiation and a prognostic locus for human
      osteoporosis. This short overview summarizes some of the cellular, molecular, and
      crosstalk signaling mechanisms that control osteoclast and osteoblast
      differentiation and activation.

PMID- 23551106
TI  - Introduction to inositol phospholipid signaling in physiology and disease.

PMID- 23551107
TI  - Self-assembled Fe2O3/graphene aerogel with high lithium storage performance.
AB  - In this study, graphene aerogel (GA)-supported Fe2O3 particles with three
      dimensional (3D) architecture was prepared by a one-pot hydrothermal process.
      Fe2O3 particles were dispersed uniformly on the graphene sheets, and the
      resulting composites self-assembled into a 3D network via hydrothermal treatment.
      This strategy provides a facile and environmentally friendly method for the large
      scale synthesis of Fe2O3/GAs without any additional reductant. As the anode
      material for lithium ion batteries, the Fe2O3/GAs in this study manifested an
      excellent reversible capacity of 995 mA h g(-1) after 50 cycles at a charge
      discharge rate of 100 mA g(-1) and even delivered reversible capacity as high as
      372 mA h g(-1) at a high rate of 5000 mA g(-1). The outstanding electrochemical
      performance of Fe2O3/GAs can be attributed to the synergistic interaction between
      uniformly dispersed Fe2O3 particles and graphene aerogel, in which a robust 3D
      framework of graphene provided highly conductive networks with a large surface
      area and short diffusion path length for the transport of lithium ions.

PMID- 23551108
TI  - Maternal outcomes in women supplemented with a high-protein drink in labour.
AB  - BACKGROUND: Because of the potential aspiration risk, oral intake is restricted
      during labour. AIMS: To determine whether high-protein drink supplementation in
      labour decreases nausea and emesis and promotes patient satisfaction. MATERIALS
      AND METHODS: The study was registered with www.clinicaltrials.gov (NCT01414478).
      Labouring women were randomised into two groups: Group P received a high-protein
      drink (325 mL) with ice chips/water PRN; and Group C served as control and
      received only ice chips/water PRN (Study 1). Incidences of nausea and emesis were
      measured hourly until delivery and at 1 h postdelivery. Patient satisfaction was
      measured the following day. A secondary aim was to evaluate the rate of gastric
      emptying (t1/2 ) in women who ingested either 325 mL of a high-protein drink or
      ice chips/water (Study 2) using ultrasound. RESULTS: In Study 1, 150 women were
      recruited (Group P = 75; Group C = 75). There were no differences in the overall
      incidences of nausea (P = 0.14), emesis (P = 0.15) or in the incidences at the
      measured time periods (MANOVA, P > 0.05). Median patient satisfaction scores were
      higher in Group P than in Group C (P = 0.007). In Study 2, 18 additional patients
      (Group PG = 9; Group CG = 9) were analysed to determine US gastric emptying t1/2
      rates (PG : 25.56 +/- 15.90 min [95% CI: 15.17 - 35.94] compared with CG : 20.00
      +/- 8.70 min [95% CI: 14.34 - 25.66], P = 0.19). CONCLUSION: In labour, patient
      satisfaction is improved with high-protein drink supplementation compared with
      ice chips/water with comparable gastric emptying rates.

PMID- 23551109
TI  - [131I]IAZA as a molecular radiotherapeutic (MRT) drug: wash-out with cold IAZA
      accelerates clearance in a murine tumor model.
AB  - Based on animal model studies, [131I]IAZA may be useful as an adjunct
      radiotherapeutic (MRT) drug for the treatment of tumor hypoxia. However,
      radioactivity in the blood of patients and healthy volunteers dosed with
      [123I]IAZA has a protracted terminal elimination phase in which clearance is
      influenced by free [123I]IAZA and possibly by unidentified metabolites. The
      current work reports that about 40% of the radioactivity in human serum is
      associated with the serum protein fraction, and that the free:bound ratio is
      constant at about 60:40 for at least the first 135 min after injection, as
      determined by radio-HPLC analyses. In order to modulate the clearance of bound
      and free radioactive IAZA, nonradioactive (cold) IAZA was administered i.v. 1 h
      following injection of high specific activity [125I][IAZA in the Balb/C EMT-6
      murine tumor model. This 'wash out' procedure reduced the concentrations of
      radioactivity by at least 40% in all tissues, with greatest effect in kidney and
      liver, and least in tumor. As a result, the tumor:blood ratio increased from 5.8
      to 8.5 at 4 h post-injection. This effect would be advantageous for the use of
      [131I]IAZA as an MRT drug. Optimization of intervals between radioactive and wash
      out dose, and confirmation of the self-irradiation dose to all tissues, remain to
      be undertaken before [131I]IAZA can be tested as a low-dose-rate MRT supplement
      to external beam x-ray radiotherapy.

PMID- 23551110
TI  - Comparing high LET 227Th- and low LET 177Lu-trastuzumab in mice with HER-2
      positive SKBR-3 xenografts.
AB  - The aim of the present study was to compare the biodistribution, normal tissue
      toxicity and therapeutic effect of the alpha-particle emitting 227Th-trastuzumab
      and the beta-particle emitting 177Lu-trastuzumab in mice with HER2- expressing
      SKBR-3 breast cancer xenografts. METHODS: Biodistributions of the two
      radioimmunoconjugates were determined at different time points after i.v.
      injection. Inhibition of tumor growth was measured after single injection of
      227Th-trastuzumab (200, 400, 600 or 1000 kBq/kg), 177Lu-trastuzumab (40 or 200
      MBq/kg) or saline. The toxicity profiles were compared by measurements of body
      weight,clinical chemistry and hematological parameters, as well as histological
      examination of tissue specimens. RESULTS: 400 kBq/kg of 227Th-trastuzumab and 40
      MBq/kg of 177Lu-trastuzumab both resulted in an absorbed radiation dose to tumor
      of approximately 3 Gy. A significant anti-tumor effect and increased survival
      were observed at injected dosages of 400-1000 kBq/kg of 227Th-trastuzumab and 200
      MBq/kg of 177Lu-trastuzumab as compared to the saline control. When compared at
      the same therapeutic effect level (100% prolonged growth delay as compared to
      control) the absorbed radiation dose of 227Th-trastuzumab was 3 times lower than
      with 177Lu-trastuzumab, indicating a relative biological effect (RBE) of 2.8 for
      227Th-trastuzumab. In contrast, when compared at the same temporary decrease of
      WBC count (50% decrease in number of white blood cells as compared to control),
      the growth delay was 3 times longer with 177Lutrastuzumab than with 227Th
      trastuzumab, which indicates that the therapeutic index was three times higher
      for 177Lutrastuzumab than for 227Th-trastuzumab. CONCLUSION: In this xenograft
      model the RBE was higher for 227Th-trastuzumab than for 177Lu-trastuzumab, while
      the therapeutic index of 177Lu-trastuzumab was superior to that of 227Th
      trastuzumab.

PMID- 23551111
TI  - Targeted alpha therapy with 227Th-trastuzumab of intraperitoneal ovarian cancer
      in nude mice.
AB  - The aim of the current study was to investigate the therapeutic effect of 227Th
      radioimmunotherapy on intraperitoneally growing human bioluminescent HER2
      positive ovarian cancer cells. METHODS: In vitro toxicity of 227Th-trastuzumab in
      bioluminescent SKOV3-luc-D3 ovarian cancer cells was assessed in a growth assay.
      The biodistribution of intraperitoneally administrated 227Th-trastuzumab in
      athymic nude mice without tumor cells was determined. For in vivo therapy,
      seventy female athymic nude mice were intraperitoneally inoculated with tumor
      cells 17 days prior to injection of single 227Th-trastuzumab doses of 1000
      kBq/kg, 600 kBq/kg or 400 kBq/kg, or three injections with 400 kBq/kg 227Th
      trastuzumab separated by 4 weeks. Two control groups were given either 20 ug
      unlabeled trastuzumab or 0.9% NaCl. In vivo bioluminescence imaging was performed
      weekly before and after onset of therapy. Tumor growth, survival and toxicity
      were compared. RESULTS: There was a statistically significant therapeutic effect
      of the 227Th-trastuzumab treatment both with respect to survival and tumor
      growth. The maximum tolerated dosage was 600 kBq/kg 227Th-trastuzumab. In the in
      vitro study, two hours incubation with 20 kBq/ml of 227Th-trastuzumab, followed
      by washing, and subsequent culture of the cells resulted in an average absorbed
      radiation dose of 6 Gy after 11 days and complete growth inhibition. CONCLUSION:
      Targeted alpha therapy with 227Th-trastuzumab of human SKOV3-luc-D3 cells growing
      intraperitoneally in nude mice was clearly superior to unlabeled trastuzumab
      therapy. The results warrant further studies of 227Th-radioimmunotherapy used as
      adjuvant treatment and for metastatic cancer.

PMID- 23551112
TI  - Phage biocontrol of enteropathogenic and Shiga toxin-producing Escherichia coli
      during milk fermentation.
AB  - Two bacteriophages, isolated from faeces, were assayed as biocontrol agents of
      pathogenic Escherichia coli during milk fermentation. Phage DT1 was tested on the
      strain E. coli DH5alpha, one enteropathogenic E. coli (EPEC) strain and one Shiga
      toxigenic E. coli O157:H7 (STEC) strain. Phage DT6 was tested on two STEC strains
      (O157:H7 and non-O157). One additional assay was performed by using a cocktail of
      both phages against the O157:H7 STEC strain. Streptococcus thermophilus 10-C, the
      strain used as lactic starter, reached 10(9)  CFU ml(-1) after 4 h, while pH
      values fell to 4.5 after 8 h, regardless of the presence of E. coli strains
      and/or phages. In absence of phages, E. coli strains reached 4-6 log CFU ml(-1)
      at 5-6 h. Escherichia coli DH5alpha and O157:H7 STEC strains were rapidly and
      completely inactivated by phage DT1 and phage cocktail, respectively, while
      O157:H7 STEC was completely inactivated either by DT1 or by DT6, after 8 h. The
      EPEC strain was not detected at 1 h (<10 CFU ml(-1) ) but grew afterwards, though
      at lower rates than without phage. For non-O157:H7 STEC, reductions lower than 1
      log CFU ml(-1) were observed for all sampling times. Phages DT1 and DT6, either
      individually or as a cocktail, effectively reduce O157:H7 STEC counts during milk
      fermentation, without compromising the starter culture performance. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Coliphages DT1 and DT6, isolated from faeces and
      selected on the basis of their host range, showed to be valuable tools for the
      control of pathogenic Escherichia coli during milk fermentation, without
      compromising the starter culture performance. Both phages, either individually or
      as a cocktail, may function as an extra safety barrier beyond traditional
      pasteurization, effectively reducing O157:H7 Shiga toxin-producing Escherichia
      coli (STEC) counts during early growth, thus avoiding Shiga toxin production and
      accumulation.

PMID- 23551113
TI  - Identifying infants at high-risk for second-hand smoke exposure.
AB  - BACKGROUND: To examine the social determinants of infant smoke exposure and
      whether these associations vary by mothers' smoking status and number of children
      in the household. METHODS: There were 135 278 mothers from 28 states who
      participated in the Pregnancy Risk Assessment Monitoring System from 2000 to
      2003. RESULTS: Overall 9.9% of mothers reported that her infant was in the same
      room as someone smoking for 1 or more hours per day. Among smoking households,
      infants with 1 or 2+ siblings were 25% and 59% more likely to be exposed to 1+
      hours of second-hand smoke daily, respectively, than infants with no siblings.
      CONCLUSION: Infants only a few months old are being exposed to second-hand smoke,
      particularly infants whose mother smokes and infants with siblings, indicating
      the importance of surveillance even for this young age group.

PMID- 23551114
TI  - Parental perception of child weight: a concept analysis.
AB  - AIM: This article is a report of an analysis of the concept of parental
      perception of child weight. BACKGROUND: Perception is commonly studied, but lacks
      a strong conceptual definition. Concept analysis is important in providing a
      conceptual definition of parental perception of child weight. DESIGN: Rodgers's
      evolutionary view of concept analysis guided this enquiry. DATA SOURCES: A search
      of multiple nursing and social sciences databases was undertaken, including
      CINAHL, Academic Search Complete, Science Direct, ProQuest, PsychINFO, Medline
      and SocINDEX. REVIEW METHODS: Data from 2000-2012 related to the concept of
      interest were reviewed. Fifty-eight articles meeting the inclusion criteria were
      included. Key attributes, antecedent occurrences and consequences of the
      concept's use were identified. Thematic analysis revealed common themes related
      to the concept attributes, antecedents and consequences. RESULTS: Five attributes
      were identified including: parental recognition of body size, physical
      appearance, functional abilities, psychosocial effects and health effects related
      to body weight. Antecedents of this concept are parental beliefs and values about
      body weight, fatalism, societal normalization of overweight, parental weight
      status and parental mental health status. The consequences of this concept are
      parental concern, increased knowledge about obesity-related health risks,
      motivation to make changes and family lifestyle changes. The ultimate goal is a
      healthy weight for the child. CONCLUSIONS: A middle-range explanatory theory of
      parental perception of child weight was proposed. Parents who recognize child
      weight issues may be motivated to initiate lifestyle changes, resulting in a
      healthy weight for the child.

PMID- 23551115
TI  - Potential role for human P-glycoprotein in the transport of lacosamide.
AB  - PURPOSE: Antiepileptic drugs (AEDs) do not effectively treat 30-40% of patients
      with epilepsy. Export of AEDs by P-glycoprotein (Pgp, ABCB1, or MDR1), which is
      overexpressed in the blood-brain barrier in drug-resistant patients, may be a
      mechanism for resistance to AEDs. For most recently approved AEDs, whether they
      are transported by Pgp is unknown. We investigated whether a new AED, lacosamide
      (LCM), is a substrate of human Pgp. METHODS: LLC-PK1 and MDCKII cells transfected
      with the human MDR1 gene were used to determine the substrate status of LCM in
      concentration equilibrium transport assays (CETAs). An equal concentration of
      drug was initially loaded in both the apical and basal chambers, and the
      concentration in both chambers was measured up to 4 h. The experiments were
      repeated in the presence of the Pgp inhibitors verapamil and tariquidar. Caco-2
      assays were used to determine the intrinsic permeability and efflux ratio of LCM
      as well as its potential to inhibit digoxin, a Pgp substrate. KEY FINDINGS:
      Lacosamide was transported by MDR1-transfected cells from basolateral to apical
      sides. The efflux of LCM could be completely blocked by verapamil or tariquidar.
      In Caco-2 assays, LCM showed high permeability without a significant efflux
      ratio; it did not inhibit digoxin, a Pgp substrate. SIGNIFICANCE: Although LCM is
      a substrate of Pgp in CETA, Caco-2 data demonstrated that passive diffusion
      should play a major role in the overall disposition of LCM. The critical role of
      Pgp should be addressed in vivo.

PMID- 23551116
TI  - When opportunity matters: comparing the risk-taking attitudes of prisoners and
      recently released ex-prisoners.
AB  - Risk-taking tendencies and environmental opportunities to commit crime are two
      key features in understanding criminal behavior. Upon release from prison, ex
      prisoners have a much greater opportunity to engage in risky activity and to
      commit criminal acts. We hypothesized that ex-prisoners would exhibit greater
      risk-taking tendencies compared to prisoners who have fewer opportunities to
      engage in risky activity and who are monitored constantly by prison authorities.
      Using cumulative prospect theory to compare the risky choices of prisoners and ex
      prisoners our study revealed that ex-prisoners who were within 16 weeks of their
      prison release made riskier choices than prisoners. Our data indicate that
      previous studies comparing prisoners behind bars with nonoffenders may have
      underestimated the risk-taking tendencies of offenders. The present findings
      emphasize the central role played by risk-taking attitudes in criminal offending
      and highlight a need to examine offenders after release from prison. 

PMID- 23551117
TI  - Gonadal mosaicism as a rare cause of autosomal recessive inheritance.
AB  - Autosomal recessive diseases are typically caused by the biparental inheritance
      of familial mutant alleles. Unusual mechanisms by which the recessiveness of a
      mutant allele is unmasked include uniparental isodisomy and the occurrence of a
      de novo chromosomal rearrangement that disrupts the other allele. Gonadal
      mosaicism is a condition in which a postfertilization mutation is confined to the
      gamete precursors and is not detected in somatic tissues. Gonadal mosaicism is
      known to give the impression of autosomal recessive inheritance when recurrence
      of an autosomal-dominant condition among offspring of phenotypically normal
      parents is observed. Here, we report an extremely rare event in which maternal
      gonadal mosaicism for a recessive mutation in COL4A4 caused the recurrence of
      Alport syndrome within a consanguineous family. Such rare occurrence should be
      taken into account when analyzing pedigrees both for clinical and research
      purposes. 

PMID- 23551118
TI  - Proteomic analysis of a twin-arginine translocation-deficient mutant unravel its
      functions involved in stress adaptation and virulence in fish pathogen
      Edwardsiella tarda.
AB  - Edwardsiella tarda is a Gram-negative, facultative aerobic pathogen which infects
      multifarious hosts including fish, amphibians and human beings. A twin-arginine
      translocation (Tat) gene cluster important for high-salt tolerance in E. tarda
      was identified previously. Here the genetic structure and pleiotropic roles of
      the Tat system in physiological adaptation of the bacterium were further
      characterized. Functional analysis indicated that tatD was not required for Tat
      export process and tatE might be an allelic gene of tatA in the bacterium. The
      results showed that disruption in the Tat system did not affect the morphology
      and biofilm formation in E. tarda, but did affect motility, hemagglutination,
      cell aggregation and infection of eukaryotic cells (e.g. macrophage J774a).
      Comparative proteomics analysis of subcellular proteins using two-dimensional gel
      electrophoresis and a qualitative shotgun protein sequencing method were
      implemented to identify proteins differentially expressed in E. tarda EIB202 vs.
      ?tatABCD. The results revealed a large repertoire of differentially expressed
      proteins (n = 61), shedding light on the Tat system associated with virulence and
      stress-associated processes in E. tarda.

PMID- 23551119
TI  - A new view of an unusual pacemaker complication: role of three-dimensional
      transthoracic echocardiography.
AB  - Tricuspid regurgitation (TR) produced by endocavitary leads (EL) from permanent
      pacemakers and implantable cardiac defibrillators is a well-known complication of
      this procedure. The EL may damage or interfere with tricuspid valve function
      causing mechanical interference of the valve leaflets leading to incomplete valve
      closure. It is important to recognize this mechanical complication because it
      could be corrected by repositioning the lead. In this case report we demonstrate
      how three-dimensional transthoracic echocardiography permits to obtaining an en
      face view, which allows simultaneous visualization of the 3 moving leaflets
      during the cardiac cycle, their attachment to the tricuspid annulus and the
      pattern of leaflet coaptation. Thus, we propose three-dimensional transthoracic
      echocardiography as the tool of choice to evaluate TR related to EL, to evaluate
      the necessity of repositioning the lead if severe regurgitation or tricuspid
      valve malfunction are demonstrated. 

PMID- 23551120
TI  - Suspected isolated pancreatic enzyme deficiencies in dogs.

PMID- 23551122
TI  - Biomimetic synthesis of TiO2-SiO2-Ag nanocomposites with enhanced visible-light
      photocatalytic activity.
AB  - Ternary TiO2-SiO2-Ag nanocomposites with enhanced visible-light photocatalytic
      activity have been synthesized through a facile biomimetic approach by utilizing
      lysozyme as both inducing agent of TiO2 and reducing agent of Ag(+). TiO2
      nanoparticles (~280 nm) are at first fabricated by the inducing of lysozyme.
      Afterward, SiO2 layers are formed as "pancakes" stuck out of TiO2 nanoparticles
      through a sol-gel process. Finally, Ag nanocrystals (~24.5 nm) are deposited onto
      the surface of TiO2-SiO2 composites via the reduction of lysozyme, forming TiO2
      SiO2-Ag nanocomposites. The resultant nanocomposites display a high
      photocatalytic activity for the degradation of Rhodamine B under the visible
      light irradiation, which can be attributed to the synergistic effect of enhanced
      photon absorption from the surface plasma resonance of Ag nanocrystals and the
      elevated adsorption capacity for Rhodamine B from the high specific surface area
      of SiO2. This study may provide some inspiration for the rational design and the
      facile synthesis of composite catalysts with a high and tunable catalytic
      property through a green, efficient pathway.

PMID- 23551123
TI  - Microbial diversity and prevalence of foodborne pathogens in cheap and junk foods
      consumed by primary schoolchildren.
AB  - Aerobic plate counts (APC), coliforms, Bacillus cereus, Escherichia coli and
      eight foodborne pathogens were tested in 1008 cheap and junk foods, including
      candies, dried cakes, chewing gum, chocolate, dried and seasoned seafood, ice
      cream, and sugary foods. APCs were positive for 342 samples (33.9%), and the
      majority of the counts were 2-3 log CFU g(-1) or ml(-1) (average: 1.10 log CFU g(
      1) or ml(-1) ). Most samples (97.3%) contained no coliforms (average: 0.07 log
      CFU g(-1) or ml(-1) ). Bacillus cereus was detected in 68 samples (average: 0.14
      log CFU g(-1) or ml(-1) ). Escherichia coli and Listeria monocytogenes were
      detected in 6 and 1 samples, respectively, whereas other foodborne pathogens were
      not isolated. The highest bacterial counts were associated with dried and
      seasoned seafood products and dried cakes, suggesting that appropriate
      regulations of these food types should be considered. Cheap and junk foods were
      produced mainly in developing countries, but there were no significant
      differences in the bacterial counts among different countries of origin. The
      presence of foodborne pathogens may pose a risk for children. These results
      suggest that there is cause for deeper concern about the safety of these foods
      and that effective countermeasures should be established to improve their
      microbiological safety. SIGNIFICANCE AND IMPACT OF THE STUDY: Food safety is
      especially important for children, but only limited information is available
      about the microbiological quality of cheap and junk foods that are consumed
      frequently by primary schoolchildren (e.g. dried cakes, candies and chocolates).
      The present study investigated the microbial quality of cheap and junk foods, and
      our results indicate that these foods are a potential health risk for children,
      therefore, deeper concern about the safety of these foods and effective
      countermeasures should be established to improve their microbiological safety.
      The present study may contribute to the development of an appropriate child food
      safety management system.

PMID- 23551124
TI  - Characterization of the sensitization profile to lupin in peanut-allergic
      children and assessment of cross-reactivity risk.
AB  - BACKGROUND: Case reports of allergy to lupin, due to primary sensitization or
      cross-reactions with other legumes, are increasing as a consequence of the
      augmented use of lupin flour in bakery, pasta formulations and other food items.
      The main allergens that have been associated with the sensitization to lupin are
      alpha- and beta-conglutins and, to a lesser extent, gamma- and delta-conglutin,
      but no conclusive data are available so far. The aim of this study was to
      characterize the sensitization pattern to lupin in a group of 12 Italian children
      allergic to peanut and identify the specific lupin proteins involved in the cross
      reactivity with peanut. METHODS: The immunochemical cross-reactivity among peanut
      and lupin was evaluated by both in vitro immunoblotting and in vivo fresh food
      skin prick test (FFSPT). RESULTS: The results showed that beta-conglutin was
      recognized by cutaneous IgEs from 7/12 peanut-allergic children in FFSPT and
      serum IgEs from 5/12 in immunoblotting, while 4/12 and 8/12 patients tested
      positive to gamma-conglutin in FFSPT and immunoblotting, respectively. No
      significant immunoreactive responses were observed to alpha- and delta-conglutins
      under non-reducing conditions, but they were bound in FFSPT by the sera of 5/12
      and 3/12 patients, respectively. CONCLUSION: In this group of allergic children,
      beta-conglutin has been identified as the major lupin allergen involved both in
      vitro and in vivo cross-reactivity with peanut proteins. The role of gamma
      conglutin in the cross-reactivity between lupin and peanut proteins was also
      relevant and clear, despite the observed unspecificity of the immunoblotting
      responses.

PMID- 23551121
TI  - Type 2 diabetes in East Asians: similarities and differences with populations in
      Europe and the United States.
AB  - There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian
      patients at a lower mean body mass index (BMI) compared with those of European
      descent. At any given BMI, East Asians have a greater amount of body fat and a
      tendency to visceral adiposity. In Asian patients, diabetes develops at a younger
      age and is characterized by early beta cell dysfunction in the setting of insulin
      resistance, with many requiring early insulin treatment. The increasing
      proportion of young-onset and childhood type 2 diabetes is posing a particular
      threat, with these patients being at increased risk of developing diabetic
      complications. East Asian patients with type 2 diabetes have a higher risk of
      developing renal complications than Europeans and, with regard to cardiovascular
      complications, a predisposition for developing strokes. In addition to
      cardiovascular-renal disease, cancer is emerging as the other main cause of
      mortality. While more research is needed to explain these interethnic
      differences, urgent and concerted actions are needed to raise awareness,
      facilitate early diagnosis, and encourage preventive strategies to combat these
      growing disease burdens.

PMID- 23551125
TI  - Echocardiography allows more accurate placement of peripherally inserted central
      catheters in low birthweight infants.
AB  - AIM: The use of plain radiographs provides limited information on the placement
      of peripherally inserted central catheters (PICCs). Moreover, changes in upper
      extremity positioning cause migration of the catheters in neonates. This study
      aimed to investigate the use of echocardiography for determining catheter tip
      position, compared with plain radiographs, in low birthweight (LBW) infants in a
      tertiary neonatal intensive care unit. METHODS: The study examined the placement
      of 109 catheters in 89 infants born between September 2010 and December 2012. The
      placement of these catheters was controlled by echocardiography, with the
      patient's shoulder in adduction and the elbow in flexion. The number of catheter
      tips, echocardiographically identified within the heart, was expressed as a
      percentage of the total catheters deemed to be well positioned on plain
      radiographs. RESULTS: The number of catheter tips that were echocardiographically
      identified within the heart was significant (25%, p < 0.001). Twenty-three
      catheters were repositioned to be outside of the heart, without any
      complications. CONCLUSION: This study demonstrated the value of echocardiography
      for identifying the positioning of catheter tips in LBW infants.
      Echocardiography, coupled with initial plain radiographs, should be the gold
      standard for assessing PICC tip positions in those infants.

PMID- 23551126
TI  - Hypoxia-inducible factor and signal transducer and activators of transcription 3:
      two central regulators meet to regulate kidney pathophysiology.

PMID- 23551127
TI  - Routine early versus deferred provisional tirofiban treatment in patients with
      acute coronary syndrome undergoing percutaneous coronary intervention.
AB  - The present study examined the optimal timing of tirofiban administration in
      moderate- or high-risk non-ST segment elevated acute coronary syndrome (NSTE-ACS)
      patients undergoing percutaneous coronary intervention (PCI). Eligible patients
      were randomized into two groups. Tirofiban was administered routinely at >= 4 h
      before angiography (routine early group; n = 141 patients) or provisionally only
      for bailout after angiography (deferred provisional group; n = 145 patients). The
      parameters analysed were: creatine kinase MB isoenzyme (CK-MB), thrombolysis in
      myocardial infarction (TIMI) flow, thrombotic complications during PCI, efficacy
      end-points (death, myocardial infarction or target vessel revascularization) at
      7, 30 and 180 days and safety end-points (bleeding or thrombocytopenia). In the
      deferred provisional group, 48 patients (33.1%) required bailout tirofiban.
      Tirofiban was administered 5.8 h earlier in the routine early compared with the
      deferred provisional group. The routine early group showed a lower percentage
      increase in CK-MB (in U/L) 12-24 h after PCI compared with the deferred
      provisional group (0 (-4.0, 3.0) vs 0.4 (-3.0, 5.0), respectively; P = 0.045), as
      well as higher pre-PCI TIMI 3 (i.e. normal) flow (78.7% vs 64.8%, respectively; P
      = 0.042) and a lower incidence of thrombotic events (5.0% vs 33.1%, respectively;
      P < 0.0001). There were no significant differences in efficacy and safety end
      points. In patients with moderate- or high-risk NSTE-ACS, early tirofiban
      combined with dual antiplatelet therapy was associated with better patency before
      PCI, attenuated minor myocardial damage and a lower prevalence of thrombotic
      complications during PCI, but had no significant benefit on the post-PCI TIMI 3
      flow or short-term prognosis.

PMID- 23551128
TI  - Role of the cytoskeleton in communication between L-type Ca(2+) channels and
      mitochondria.
AB  - The L-type Ca(2+) channel is the main route for Ca(2+) entry into cardiac
      myocytes, which is essential for the maintenance of cardiac excitation and
      contraction. Alterations in L-type Ca(2+) channel activity and Ca(2+) homeostasis
      have been implicated in the development of cardiomyopathies. Cardiac excitation
      and contraction is fuelled by ATP, synthesized predominantly by the mitochondria
      via the Ca(2+)-dependent process oxidative phosphorylation. Mitochondrial
      reactive oxygen species (ROS) are by-products of oxidative phosphorylation and
      are associated with the development of cardiac pathology. The cytoskeleton plays
      a role in the communication of signals from the plasma membrane to intracellular
      organelles. There is good evidence that both L-type Ca(2+) channel activity and
      mitochondrial function can be modulated by changes in the cytoskeletal network.
      Activation of the L-type Ca(2+) channel can regulate mitochondrial function
      through cytoskeletal proteins as a result of transmission of movement from the
      beta(2)-subunit of the channel that occurs during activation and inactivation of
      the channel. An association between cytoskeletal proteins and the mitochondrial
      voltage-dependent anion channel (VDAC) may play a role in this response. The L
      type Ca(2+) channel is the initiator of contraction in cardiac muscle and the
      VDAC is responsible for regulating mitochondrial ATP/ADP trafficking. This
      article presents evidence that a functional coupling between L-type Ca(2+)
      channels and mitochondria may assist in meeting myocardial energy demand on a
      beat-to-beat basis.

PMID- 23551129
TI  - Request for retraction: Short interfering RNA (siRNA) as a novel therapeutic.

PMID- 23551130
TI  - Request for the retraction of Cepp review 33: 504-510 (2006).

PMID- 23551131
TI  - The relationship between the Young's modulus of the stratum corneum and age: a
      pilot study.
AB  - BACKGROUND/PURPOSE: The mechanical properties of the stratum corneum play an
      important role in protecting the body from external physical stimuli and
      excessive sensitivity. However, it is difficult to analyze these mechanical
      properties in vivo. To resolve this problem, we carried out a numerical analysis
      to calculate the Young's modulus of the stratum corneum. We then investigated the
      relationship between the Young's modulus of the stratum corneum and age. METHODS:
      We used a Cutometer((r)) and a Dermal Torque Meter((r)) for measuring skin
      mechanical parameters, and optical coherence tomography and an ultrasonic imaging
      system for measuring skin thickness. Based on these non-invasive results, liner
      elastic analysis was performed by the finite element method, and the Young's
      moduli of the stratum corneum and the dermis were calculated by solving an
      inverse problem. Using these techniques, we analyzed the correlation between the
      Young's modulus of the stratum corneum for the cheeks of seventy-eight Japanese
      women aged from 20 to 68 years. RESULTS: In the group study, the mean Young's
      moduli of the stratum corneum and dermis were calculated 1.993 MPa and 0.066 MPa,
      respectively. While carrying out individual analyses, there was a weak
      relationship between the Young's modulus of the stratum corneum and age (r =
      0.337). CONCLUSION: We calculated the Young's modulus of the stratum corneum in
      vivo, with commercially available systems, and found that it is a weak
      correlation with age in this group of subjects. Future developments of our method
      would be beneficial in the characterization of facial skin aging and the
      validation of cosmetic and medical applications.

PMID- 23551132
TI  - Procedural justice, supervisor autonomy support, work satisfaction,
      organizational identification and job performance: the mediating role of need
      satisfaction and perceived organizational support.
AB  - AIM: To test a model linking procedural justice, supervisor autonomy support,
      need satisfaction, organizational support, work satisfaction, organizational
      identification and job performance. BACKGROUND: Research in industrial and
      organizational psychology has shown that procedural justice and supervisor
      autonomy support lead to positive outcomes. However, very little research related
      to this subject has been conducted in healthcare settings. Moreover, few studies
      have examined mechanisms that could account for these positive relationships.
      DESIGN: A cross-sectional correlational design was used. METHOD: Convenience
      sampling was used and a sample of 500 nurses working in haematology, oncology and
      haematology/oncology units in France was surveyed in 2011. The final sample
      consisted of 323 nurses (64.6% response rate). The hypothesized model was tested
      using structural equation modelling. RESULTS: Procedural justice and supervisor
      autonomy support significantly and positively influenced need satisfaction and
      perceived organizational support, which in turn positively predicted work
      satisfaction, organizational identification and job performance. CONCLUSION:
      Organizations could deliver training programmes for their managers aimed at
      enhancing the use of fair procedures in allocating outcomes and developing their
      autonomy-supportive behaviours to improve nurses' work satisfaction,
      organizational identification and job performance.

PMID- 23551133
TI  - Complications of epilepsy surgery: a systematic review of focal surgical
      resections and invasive EEG monitoring.
AB  - PURPOSE: Underutilization of epilepsy surgery remains a major problem and is in
      part due to physicians' misconceptions about the risks associated with epilepsy
      surgery. The purpose of this study was to systematically review the literature on
      complications of focal epilepsy surgery. METHODS: A literature search was
      conducted using PubMed and Embase to identify studies examining epilepsy surgery
      complications. Abstract and full text review, along with data extraction, was
      done in duplicate. Minor medical and neurologic complications were defined as
      those that resolved completely within 3 months of surgery, whereas major
      complications persisted beyond that time frame. Descriptive statistics were used
      to report complication proportions. KEY FINDINGS: Invasive monitoring: Minor
      complications were reported in 7.7% of patients, whereas major complications were
      reported in only 0.6% of patients undergoing invasive monitoring. Resective
      surgery: Minor and major medical complications were reported in 5.1% and 1.5% of
      patients respectively, most common being cerebrospinal fluid (CSF) leak. Minor
      neurologic complications occurred in 10.9% of patients and were twice as frequent
      in children (11.2% vs. 5.5%). Minor visual field defects were most common
      (12.9%). Major neurologic complications were noted in 4.7% of patients, with the
      most common being major visual field defects (2.1% overall). Perioperative
      mortality was uncommon after epilepsy surgery, occurring in only 0.4% of temporal
      lobe patients (1.2%extratemporal). SIGNIFICANCE: The majority of complications
      after epilepsy surgery are minor or temporary as they tend to resolve completely.
      Major permanent neurologic complications remain uncommon. Mortality as a result
      of epilepsy surgery in the modern era is rare.

PMID- 23551134
TI  - Repeat endovascular treatment of recurring hepatic artery stenoses in orthotopic
      liver transplantation.
AB  - Hepatic artery stenosis (HAS) is a complication that impacts the results of
      orthotopic liver transplantation (OLT). Interventional radiological techniques
      are important therapeutic options for HAS. The aim of this retrospective study
      was to evaluate the outcome of repeated radiological treatments in recurring HAS
      after OLT. Of the 941 patients who underwent OLT at our center from January 1998
      to September 2010, 48 (5%) were diagnosed with HAS, 37 (77%) of whom underwent
      transluminal interventional therapy with the placement of an endovascular stent.
      Success rate, complications, hepatic artery patency and follow-up were reviewed.
      After stent placement, artery patency was achieved in all patients. Three
      patients developed complications, including arterial dissection and hematoma. HAS
      recurrence was observed in 9 patients (24%), and hepatic artery thrombosis (HAT)
      occurred in 4 (11%). Radiological interventions were repeated 10 times in 8
      patients without complications. At a median follow-up of 66 months (range 10
      158), hepatic artery patency was observed in 35 cases (94.6%). The 5-year rates
      for graft and patient survival were 82.3% and 87.7%, respectively. Restenosis may
      occur in one-third of patients after endovascular treatment for thrombosis and
      HAS, but the long-term outcomes of iterative radiological treatment for HAS
      indicate a high rate of success.

PMID- 23551135
TI  - Phenotypic evidence that the function of the [Fe]-hydrogenase Hmd in
      Methanococcus maripaludis requires seven hcg (hmd co-occurring genes) but not
      hmdII.
AB  - The H2 -dependent methylene-tetrahydromethanopterin dehydrogenase (Hmd), also
      known as the [Fe]-hydrogenase, is found only in methanogens without cytochromes.
      In contrast to the binuclear metal centers of the [NiFe]- and [FeFe]
      hydrogenases, the [Fe]-hydrogenase contains only a single Fe atom, which is
      coordinated by a novel guanylylpyridinol cofactor in the active site. The
      biosynthesis of the cofactor is not well understood and the responsible genes are
      unknown. However, seven genes (hmd co-occurring genes, hcg) encoding proteins of
      unknown function are always associated with the hmd gene. In the model methanogen
      Methanococcus maripaludis, we used a genetic background in which a deletion of
      hmd had a distinct growth phenotype, and made null-mutations in each hcg gene as
      well as in a gene encoding the Hmd paralog HmdII, which is hypothesized to
      function as a scaffold for cofactor synthesis. Deletions in all seven hcg genes
      resulted in the same growth phenotype as a deletion in hmd, suggesting they are
      required for Hmd function. In all cases, genetic complementation of the mutation
      restored the wild-type phenotype. A deletion in hmdII had no effect.

PMID- 23551136
TI  - Incremental value of transthoracic real time three-dimensional echocardiography
      in assessment of a right ventricular mass.
AB  - A 52-year-old male with a right ventricular mass that filled the entire right
      ventricle and assumed its shape was evaluated by two-dimensional and real time
      three-dimensional (3D) echocardiography. Contrast enhanced 3D imaging and
      quantitative assessments of the size of the mass were performed. The clinical
      correlation, the imaging characteristics of the mass, and the pattern of
      vascularity were consistent with metastatic hepatocellular carcinoma. The case
      illustrates the incremental role of 3D echo in defining the size, shape, spatial
      relationship, attachments, consistency, and vascularity of the right ventricular
      mass.

PMID- 23551137
TI  - Study to assess in vitro antimicrobial activity of nine ear cleaners against 50
      Malassezia pachydermatis isolates.
AB  - BACKGROUND: Ear cleaning is an important part of the successful therapy of otitis
      externa. HYPOTHESIS/OBJECTIVES: To evaluate the in vitro activity of nine
      commercially available ear cleaners (Cerumaural((r)), CleanAural Dog((r)), Epi
      Otic((r)), MalAcetic Aural((r)), Otoclean((r)), Otodine((r)), Sancerum((r)),
      Surosolve((r)) and TrizUltraTM + Keto) against 50 Malassezia pachydermatis
      isolates from clinical cases of canine otitis externa. To the authors' knowledge,
      this is the first study to analyse the in vitro susceptibility of a large number
      of M. pachydermatis isolates to a variety of ear cleaner products. ANIMALS: Forty
      nine hospital population dogs diagnosed with otitis externa with Malassezia spp.
      present on cytological examination of ear swabs and culture. METHODS: The
      antimicrobial activity of nine ear cleaners was tested against 50 M.
      pachydermatis isolates from 49 clinical cases of canine otitis externa using an
      in vitro agar diffusion test. RESULTS: There were statistically significant
      differences in activity between ear cleaners, with five showing excellent in
      vitro anti-Malassezia activity (CleanAural Dog((r)), Epi-Otic((r)), MalAcetic
      Aural((r)), Sancerum((r)) and TrizUltraTM + Keto), two moderate activity
      (Otodine((r)) and Surosolve((r))), one variable activity (Otoclean((r))) and one
      no activity (Cerumaural((r))). There was a significant overall difference in
      susceptibility between M. pachydermatis isolates tested (P < 0.001). CONCLUSIONS
      AND CLINICAL IMPORTANCE: Ear cleaners with activity against Malassezia may help
      to reduce the unnecessary use of antibiotic-containing polypharmaceutical ear
      medications. This study shows that the use of a large number of isolates may
      provide a more accurate account of the in vitro activity of a product.

PMID- 23551139
TI  - Influence of coffee (Coffea arabica) and galacto-oligosaccharide consumption on
      intestinal microbiota and the host responses.
AB  - Although studies have reported numerous effects of coffee on human health, few
      studies have examined its specific effects on gut microbiota. This study aimed to
      clarify the influence of coffee and galacto-oligosaccharide (GOS) consumption on
      gut microbiota and host responses. After mice consumed coffee and GOS, their
      intestines were sampled, and the bacterial counts were measured with quantitative
      RT-PCR. Results showed that GOS consumption significantly increased total
      bacteria counts in the proximal colon. Although Escherichia coli and Clostridium
      spp. counts significantly decreased in the proximal colon, Bifidobacterium spp.
      counts increased remarkably in the same area. A bacterial growth inhibition assay
      was also conducted, and the results showed that E. coli growth was inhibited only
      by a coffee agar. Host responses were also investigated, revealing that coffee
      and GOS consumption remarkably increased aquaporin8 expression in the proximal
      colon. In conclusion, coffee has antibiotic effects, and GOS significantly
      decreased E. coli and Clostridium spp. counts, but increased Bifidobacterium spp.
      counts remarkably. Aquaporin8 expression was also increased with a mixture of
      coffee and GOS consumption. This is the first study to demonstrate that coffee
      consumption can regulate gut microbiota and increase aquaporin8, both of which
      are necessary for maintaining intestinal balance.

PMID- 23551138
TI  - Nucleus accumbens GABAergic inhibition generates intense eating and fear that
      resists environmental retuning and needs no local dopamine.
AB  - Intense fearful behavior and/or intense appetitive eating behavior can be
      generated by localized amino acid inhibitions along a rostrocaudal anatomical
      gradient within medial shell of nucleus accumbens of the rat. This can be
      produced by microinjections in medial shell of either the gamma-aminobutyric acid
      (GABA)A agonist muscimol (mimicking intrinsic GABAergic inputs) or the AMPA
      (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) antagonist DNQX (6,7
      dinitroquinoxaline-2,3-dione), disrupting corticolimbic glutamate inputs). At
      rostral sites in medial shell, each drug robustly stimulates appetitive eating
      and food intake, whereas at more caudal sites the same drugs instead produce
      increasingly fearful behaviors such as escape, distress vocalizations and
      defensive treading (an antipredator behavior rodents emit to snakes and
      scorpions). Previously we showed that intense motivated behaviors generated by
      glutamate blockade require local endogenous dopamine and can be modulated in
      valence by environmental ambience. Here we investigated whether GABAergic
      generation of intense appetitive and fearful motivations similarly depends on
      local dopamine signals, and whether the valence of motivations generated by
      GABAergic inhibition can also be retuned by changes in environmental ambience. We
      report that the answer to both questions is 'no'. Eating and fear generated by
      GABAergic inhibition of accumbens shell does not need endogenous dopamine. Also,
      the appetitive/fearful valence generated by GABAergic muscimol microinjections
      resists environmental retuning and is determined almost purely by rostrocaudal
      anatomical placement. These results suggest that nucleus accumbens GABAergic
      release of fear and eating are relatively independent of modulatory dopamine
      signals, and more anatomically pre-determined in valence balance than release of
      the same intense behaviors by glutamate disruptions.

PMID- 23551140
TI  - Feline musculoskeletal pain index: responsiveness and testing of criterion
      validity.
AB  - BACKGROUND: Progress in establishing if therapies provide relief to cats with
      degenerative joint disease (DJD)-associated pain is hampered by a lack of
      validated owner-administered assessment methods. HYPOTHESIS: That an
      appropriately developed subjective owner-completed instrument (Feline
      Musculoskeletal Pain Index-FMPI) to assess DJD-associated impairment would have
      responsiveness and criterion validity. ANIMALS: Twenty-five client-owned cats
      with DJD-associated pain. METHODS: FMPI responsiveness (ability to detect the
      effect of an analgesic treatment) and validity (correlation with an objective
      measure) were explored through a stratified, randomized, double blinded, placebo
      controlled, crossover 10-week clinical study. Meloxicam was administered to
      effect pain relief. A linear mixed model, backward stepwise regression, and
      Pearson correlations were used to assess responsiveness and criterion validity
      with the assumption that the NSAID would increase activity. RESULTS: Positive
      responses of cats to placebo (P = .0001) and meloxicam treatment (P = .0004) were
      detected; however, the instrument did not detect any difference between placebo
      and meloxicam (linear mixed model), even for the high impairment cases. Percent
      meloxicam target dose administered, temperament, and total baseline FMPI score
      were covariates that most affected FMPI scores. Controlling for significant
      covariates, most positive effects were seen for placebo treatment. Positive
      treatment effects on activity were detected, but only for the cases designated as
      most highly impaired. CONCLUSIONS AND CLINICAL IMPORTANCE: Neither responsiveness
      nor criterion validity were detected by the inclusion criteria for cases in this
      study. The data suggest that further work is indicated to understand factors
      affecting activity in cats to optimize inclusion criteria.

PMID- 23551141
TI  - Congenital malformations of the vertebral column in ancient amphibians.
AB  - Temnospondyls, the largest group of Palaeozoic and Mesozoic amphibians,
      primitively possess rhachitomous vertebrae with multipartite centra (consisting
      of one horse-shoe-shaped inter- and paired pleurocentra). In a group of
      temnospondyls, the stereospondyls, the intercentra became pronounced and disc
      like, whereas the pleurocentra were reduced. We report the presence of congenital
      vertebral malformations (hemi, wedge and block vertebrae) in Permian and Triassic
      temnospondyls, showing that defects of formation and segmentation in the tetrapod
      vertebral column represent a fundamental failure of somitogenesis that can be
      followed throughout tetrapod evolution. This is irrespective of the type of
      affected vertebra, that is, rhachitomous or stereospondylous, and all components
      of the vertebra can be involved (intercentrum, pleurocentrum and neural arch),
      either together or independently on their own. This is the oldest known
      occurrence of wedge vertebra and congenital block vertebra described in fossil
      tetrapods. The frequency of vertebral congenital malformations in amphibians
      appears unchanged from the Holocene. 

PMID- 23551142
TI  - Do intravenous and subcutaneous angiotensin II increase blood pressure by
      different mechanisms?
AB  - Angiotensin (Ang) II plays a key role in blood pressure regulation. Mechanisms of
      the pressor effect of chronic intravenous AngII administration include
      vasoconstriction, stimulation of the sympathetic nervous system and aldosterone
      production, as well as direct effects on renal excretion of sodium and water. 
      Chronic AngII administration by subcutaneous minipump at doses higher than
      required to increase blood pressure by the intravenous route has identified
      additional pressor mechanisms, including the immune system, cytokines and matrix
      metalloproteinases. However, pressor doses of subcutaneous AngII may exceed the
      angiotensinogen synthesis rate and produce inflammation, fibrosis and necrosis of
      skin overlying the minipump.  Evidence that chronic subcutaneous and intravenous
      AngII increase blood pressure by different mechanisms includes the prevention of
      the pressor effects of subcutaneous, but not intravenous, AngII by angiotensin
      converting enzyme inhibition. Furthermore, low doses of subcutaneous AngII reduce
      blood pressure of female, but not male, rodents and higher doses are less pressor
      in females than in males, whereas intravenous AngII is equally pressor in males
      and females.  Pressor doses of chronic subcutaneous AngII produce greater weight
      loss, anorexia and reduced kidney weight and cause greater vascular, cardiac and
      renal pathology than equally pressor doses of chronic intravenous AngII.  The
      different effects of chronic intravenous and subcutaneous AngII suggest that
      these two models of hypertension give different information and may differ in
      their relevance to blood pressure regulation in physiological and pathological
      states such as hypertension in humans. 

PMID- 23551143
TI  - The family meal panacea: exploring how different aspects of family meal
      occurrence, meal habits and meal enjoyment relate to young children's diets.
AB  - The general consensus in the research to date is that family meals are linked to
      healthier eating habits in children, compared to not eating with the family. Yet,
      few studies explore what it is about commensality which leads to better food
      choices among children. Using a representative Scottish sample of five-year-old
      children, this research explores the extent to which family meal occurrence, meal
      patterns regarding where, when and with whom children eat and perceived meal
      enjoyment predict the quality of children's diets after controlling for
      indicators of maternal capital that influence both meal rituals and taste
      preferences. Eating the same food as parents is the aspect of family meals most
      strongly linked to better diets in children, highlighting the detrimental effect
      in the rise of 'children's food'. Although theoretical and empirical work pointed
      to the important health advantage in children eating together with parents, the
      results suggested that eating together was a far less important aspect of family
      meals. In evaluating the importance of the family meal, this article redirects
      attention away from issues of form and function towards issues of food choice.
      Policy implications and the importance for public health to recognise the way
      eating habits are defined by and reproduce social and cultural capital are
      discussed. 

PMID- 23551144
TI  - Accuracy and usefulness of the AVOXimeter 4000 as routine analysis of
      carboxyhemoglobin.
AB  - The measurement of blood carboxyhemoglobin (CO-Hb) is important to determine the
      cause of death. The AVOXimeter 4000 (AVOX), a portable CO-oximeter, has the
      advantages of a low purchase price and operating cost, ease of operation, and
      rapid results. Little information is available on the usefulness of AVOX in the
      forensic sample, and the previous study investigated only six samples. Therefore,
      in this study, we confirmed the usefulness of the AVOX through a comparison of
      its results with data previously obtained using the double wavelength
      spectrophotometric method in autopsies. Regression analysis was performed between
      CO-Hb levels measured by the AVOX and those measured by the conventional double
      wavelength spectrophotometric method in postmortem blood samples: a significant
      correlation was observed. This study suggests the usefulness of the AVOX to
      analyze postmortem blood, and the AVOX is suitable for routine forensic analysis
      and can be applied at the crime scene. 

PMID- 23551145
TI  - Correcting for possible tissue distortion between provocation and assessment in
      skin testing: the divergent beam UVB photo-test.
AB  - BACKGROUND: In tissue viability imaging (TiVi), an assessment method for skin
      erythema, correct orientation of skin position from provocation to assessment
      optimizes data interpretation. Image processing algorithms could compensate for
      the effects of skin translation, torsion and rotation realigning assessment
      images to the position of the skin at provocation. METHODS: A reference image of
      a divergent, UVB phototest was acquired, as well as test images at varying levels
      of translation, rotation and torsion. Using 12 skin markers, an algorithm was
      applied to restore the distorted test images to the reference image. RESULTS: The
      algorithm corrected torsion and rotation up to approximately 35 degrees. The
      radius of the erythemal reaction and average value of the input image closely
      matched that of the reference image's 'true value'. CONCLUSION: The image 'de
      warping' procedure improves the robustness of the response image evaluation in a
      clinical research setting and opens the possibility of the correction of possibly
      flawed images performed away from the laboratory setting by the subject/patient
      themselves. This opportunity may increase the use of photo-testing and, by
      extension, other late response skin testing where the necessity of a return
      assessment visit is a disincentive to performance of the test.

PMID- 23551147
TI  - Highly sensitive reduced graphene oxide impedance sensor harnessing pi-stacking
      interaction mediated direct deposition of protein probes.
AB  - Graphene-based electrochemical impedance sensors have recently received much
      attention due to their outstanding sensing capability and economic viability. In
      this study, we present a novel means of constructing an impedance sensing
      platform via harnessing intrinsic pi-stacking interactions between probe protein
      molecules and reduced graphene oxide (RGO) substrate, obviating the need for
      introducing external chemical groups often required for covalent anchoring of the
      probes. To achieve this goal, protein molecules used as a probe were denatured to
      render their hydrophobic residues exposed in order to facilitate their direct pi
      stacking interactions with the surface of RGO nanosheets. The protein molecules
      in denatured form, which would otherwise have difficulty in undergoing pi
      stacking interactions with the RGO surface, were found to uniformly cover the RGO
      nanosheets at high density, conducive to providing a graphene-based impedance
      sensing platform capable of detecting a probe-specific analyte at high
      sensitivity. The proof-of-concept performance of thus-constructed RGO-based
      impedance sensors was demonstrated via selective detection of biological binding
      events of antigen-antibody reaction at a femtomolar range. Notably, since the pi
      stacking interaction can occur on the entire RGO surface, it can desirably
      exclude a backfill process indispensable for the conventional biosensors to
      suppress background noise signals. Since the procedure of pi-stacking mediated
      direct deposition of on-purpose denatured protein probes onto the RGO surface is
      facile and straightforward, the proposed strategy is anticipated to extend its
      applicability for fabrication of high performance graphene-based bio or chemical
      sensors.

PMID- 23551148
TI  - A sinus venosus atrial septal defect is diagnosed by echocardiography with an
      unusual bubble study.
AB  - A 68-year-old man underwent echocardiogram with agitated saline for a presumed
      diagnosis of primary pulmonary hypertension. Surprisingly, the bubbles from the
      agitated saline enter the left heart before filling the right side, leading to a
      diagnosis of Eisenmeger's syndrome from a sinus venosus atrial septal defect.
      Because of high right-sided pressure, the bubbles preferentially travel from the
      superior vena cava through the defect to the right superior pulmonary vein and
      left atrium, rather than the right side. This diagnosis was later confirmed on
      cardiac MRI.

PMID- 23551149
TI  - Hereditary amyloidosis caused by R554L fibrinogen Aalpha-chain mutation in a
      Spanish family and review of the literature.
AB  - BACKGROUND: Hereditary amyloidosis with predominant renal disease can be caused
      by mutations in the gene encoding the fibrinogen Aalpha-chain (AFib). Here, we
      describe the clinical course of AFib amyloidosis associated with the rare R554L
      mutation, and the significance of extrarenal amyloid deposits and their possible
      influence on cardiovascular morbidity. METHODS: We report on 101 members of a
      family after having conducted patient interviews, chart review, genetic testing,
      renal biopsies and assessment for extrarenal amyloid deposition. RESULTS: Ten
      family members had chronic kidney disease with late-onset gross proteinuria and a
      variable course of declining renal function, starting in the fourth decade of
      life. In two affected living members, we identified the AFib R554L mutation.
      Renal biopsies from two affected members revealed almost complete obliteration of
      the mesangial glomerular architecture, although kidney function was only
      moderately impaired. There was neither evidence of extrarenal amyloidosis nor
      accelerated atherosclerosis. CONCLUSIONS: Renal amyloidosis associated with the
      R554L AFib variant dominated the clinical picture in this family, which was
      similar to that associated with the much more prevalent E526V mutation. Although
      it has been hypothesized that vascular deposits of fibrinogen amyloid may be
      associated with accelerated atherosclerosis, there was no suggestion of this in
      this particular kindred.

PMID- 23551150
TI  - Comment on "Atmospheric degradation of perfluoro-2-methyl-3-pentanone:
      photolysis, hydrolysis, and hydration".

PMID- 23551151
TI  - The role of active assortment in spousal similarity.
AB  - Previous research has established the existence of active assortment, that is, a
      preference for similarity in a potential mate. Few studies, however, have
      directly related mate preferences to dyadic similarity by examining them in the
      same participants. We collected both similarity and mate preference data in two
      studies: undergraduate students (N = 519) and newlyweds (N = 335). In both
      studies, women placed a higher value on desirable personality characteristics
      (e.g., higher Conscientiousness and Agreeableness, lower Neuroticism) than did
      men. Nevertheless, our data also provided strong evidence of consensual mate
      preferences: Men and women both desired partners who were agreeable,
      conscientious, emotionally stable, intelligent, and physically attractive;
      furthermore, participants desired partners who were better (e.g., more agreeable
      and attractive) than they were. In contrast, attitudinal variables such as
      religiousness and political orientation displayed much weaker consensus but
      showed significant dyadic similarity in both samples; similarity coefficients for
      personality tended to be positive, but lower. Finally, analyses revealed a direct
      link between actual and desired similarity: Couples displayed the strongest
      similarity on those variables for which participants expressed the strongest
      preference for similarity. Our findings strongly suggest that active assortment
      is partly responsible for dyadic similarity. 

PMID- 23551152
TI  - Health-related quality of life does not mediate the protective effect of farming
      on asthma and allergic disease.

PMID- 23551153
TI  - Reply to "Comment on 'An interesting case where water behaves as a unique
      solvent. 4-Aminophthalimide emission profile to monitor aqueous environment'".

PMID- 23551154
TI  - Microencapsulation of essential oil for insect repellent in food packaging
      system.
AB  - Microcapsules containing thyme oil were prepared by in situ polymerization, using
      melamine-formaldehyde prepolymer as a wall material and 3 different emulsifiers
      (pluronic F-127, tween 80, and sodium lauryl sulfate [SLS]). The general
      characteristics and release behavior of microcapsules, and their repellent effect
      against insects were investigated. The morphology of microcapsules using SLS was
      spherical shape with smooth surface. Microcapsules began to degrade at 150 
      degrees C. The particle size ranged from 1 to 10 MUm and the loading efficiency
      of thyme oil was clearly affected by the emulsifier type. The highest loading
      efficiency appeared in microcapsules using SLS, which have good thermal
      resistance and smooth surface. The release rate of thyme oil from microcapsules
      was not only dependent on the storage temperature but also emulsifier type and
      microcapsules showed the sustained release properties for a long time. Diets,
      which were mixed with encapsulated thyme oil, expressed high insect repellent
      efficacy over 90% for 4 wk.

PMID- 23551155
TI  - Swedish child health nurses' views of early father involvement: a qualitative
      study.
AB  - AIM: To explore Swedish child health nurses' views on their role of involving
      fathers at the Child Health Centres (CHCs). METHODS: Interviews with 17
      experienced Swedish Child Health nurses were recorded, transcribed and analysed
      using systematic text condensation. Following the first analysis, the
      transtheoretical model of behavioural change was used to interpret the results.
      RESULTS: Four themes emerged during the analysis: (1) the nurses' own agenda; (2)
      nurses' opinion about the father's role; (3) nurses' gatekeeping; and (4) wanting
      more father involvement. Most nurses were in the precontemplation stage according
      to the transtheoretical model when they expressed their roles as nurses (Theme
      1), how they perceived the father's role within the family (Theme 2) and how they
      actively encouraged mothers, but not fathers, to visit the CHCs (Theme 3/Mothers
      are our priority). Nurses in the contemplation stage started to consider
      involving fathers in the CHCs (Theme 3/The gate is closed...). Still others were
      in the preparation (Theme 4/Fathers are worthy of change) and action stages
      (Theme 4/Active in involving fathers), respectively. CONCLUSION: Child Health
      nurses place more emphasis on engaging mothers than fathers in the services. To
      increase father involvement, nurses need support to become aware, initiate and
      maintain action.

PMID- 23551156
TI  - Commentary: vancomycin or metronidazole in patients with primary sclerosing
      cholangitis?

PMID- 23551157
TI  - Commentary: non-alcoholic fatty pancreas -- toward an uncharted territory.

PMID- 23551158
TI  - Commentary: non-alcoholic fatty pancreas -- toward an uncharted territory;
      authors' reply.

PMID- 23551159
TI  - Letter: symptom indexes in reflux monitoring - two are better than one.

PMID- 23551160
TI  - Letter: allopurinol co-therapy is safe and effective in autoimmune hepatitis.

PMID- 23551161
TI  - Letter: allopurinol co-therapy is safe and effective in autoimmune hepatitis --
      authors' reply.

PMID- 23551162
TI  - Depression-related behaviours displayed by female C57BL/6J mice during abstinence
      from chronic ethanol consumption are rescued by wheel-running.
AB  - Withdrawal from a chronic period of alcohol consumption is commonly associated
      with the manifestation of depression, potentially exerting a significant
      influence on treatment prospects and increasing the likelihood of relapse. Better
      therapeutic strategies need to be developed to assist with rehabilitation. Here,
      we report the detection of depression-related behaviours in a mouse model of 6
      week free-choice ethanol (10%, v/v) consumption followed by 2-week abstinence.
      Mice abstinent from alcohol showed increased immobility time on the forced-swim
      test, reduced saccharin consumption and increased latency to feed in the novelty
      suppressed feeding test. By comparison, there was no significant effect on
      anxiety-related behaviours as determined by testing on the light-dark box and
      elevated plus maze. We found that the provision of running-wheels through the
      duration of abstinence attenuated depressive behaviour in the forced-swim and
      novelty-suppressed feeding tests, and increased saccharin consumption. Given the
      link between withdrawal from addictive substances and depression, this model will
      be useful for the study of the pathophysiology underlying alcohol-related
      depression. The findings of this study establish an interaction between physical
      activity and the development of behavioural changes following cessation of
      alcohol consumption that could have implications for the development of
      rehabilitative therapies.

PMID- 23551163
TI  - Identity and stammering: negotiating hesitation, side-stepping repetition, and
      sometimes avoiding deviation.
AB  - Individuals who experience speech dysfluency are often stigmatised because their
      speech acts differ from the communicative norm. This article is located in and
      seeks to further the identity debates in exploring how individuals who are
      subject to the intermittent emergence of a stigmatised characteristic manage this
      randomised personal discrediting in their identity work. Through a series of
      focus groups and semi-structured interviews participants grudgingly report their
      management approaches which include concealing, drafting in unwitting others,
      role-playing and segregating self from their stammer. In describing how they
      manage their stammer they detail their use of the social space in a number of
      ways, including as a hiding place; a site for 'it' (the stammer); a gap in which
      to switch words; and a different area in which to perform. This study offers
      important insights, increasing our understanding of the often hidden negotiations
      of identity work and the sometime ingenious use of space in the management of a
      social stigma. 

PMID- 23551165
TI  - Prolonged febrile seizures, clinical characteristics, and acute management.
AB  - PURPOSE: Prolonged febrile seizures (PFS) lasting >=15 min have been associated
      with increased risk for epilepsy in later life. Initial treatment, mostly
      prehospital, aims to prevent its evolution to febrile status epilepticus (FSE)
      and reduce adverse outcome. Paucity of information is available on the immediate
      treatment before reaching a hospital facility. METHODS: We obtained data,
      prospectively, on all children who presented from January 2008 to March 2010 with
      PFS to the emergency rooms of four Israeli medical centers. Information related
      to seizure semiology, treatment, and medical history was collected into a
      predefined pro forma form and reviewed centrally. KEY FINDINGS: Sixty children,
      median age 18.3 months (interquartile range [IQR] 12-28) were included with a
      median seizure duration of 35 min (IQR 26-60), 43 (71.7%) lasting >=30 min.
      Seizures had focal onset in 34 infants (57%). Fifty-four families (90%) activated
      the ambulance service; median ambulance arrival time was 8 min (IQR 5-10), 33
      (61%) were medically treated by the ambulance paramedic, of whom 15 (45%)
      responded to treatment. Twelve children with active seizures did not receive
      medications. Initial treatment with rectal diazepam was more common in those with
      seizure duration >30 min. SIGNIFICANCE: Most children with PFS are treated with
      antiepileptic drugs early by the ambulance service. However, even timely
      treatment does not prevent status epilepticus in the majority of cases. These
      data highlight the need for effective early treatment of this common pediatric
      emergency.

PMID- 23551166
TI  - Brinicles as a case of inverse chemical gardens.
AB  - Brinicles are hollow tubes of ice from centimeters to meters in length that form
      under floating sea ice in the polar oceans when dense, cold brine drains downward
      from sea ice to seawater close to its freezing point. When this extremely cold
      brine leaves the ice, it freezes the water it comes into contact with: a hollow
      tube of ice-a brinicle-growing downward around the plume of descending brine. We
      show that brinicles can be understood as a form of the self-assembled tubular
      precipitation structures termed chemical gardens, which are plantlike structures
      formed on placing together a soluble metal salt, often in the form of a seed
      crystal, and an aqueous solution of one of many anions, often silicate. On one
      hand, in the case of classical chemical gardens, an osmotic pressure difference
      across a semipermeable precipitation membrane that filters solutions by rejecting
      the solute leads to an inflow of water and to its rupture. The internal solution,
      generally being lighter than the external solution, flows up through the break,
      and as it does so, a tube grows upward by precipitation around the jet of
      internal solution. Such chemical-garden tubes can grow to many centimeters in
      length. In the case of brinicles, on the other hand, in floating sea ice we have
      porous ice in a mushy layer that filters out water, by freezing it, and allows
      concentrated brine through. Again there is an osmotic pressure difference leading
      to a continuing ingress of seawater in a siphon pump mechanism that is sustained
      as long as the ice continues to freeze. Because the brine that is pumped out is
      denser than the seawater and descends rather than rises, a brinicle is a downward
      growing tube of ice, an inverse chemical garden. 

PMID- 23551164
TI  - Atypical resting-state functional connectivity of affective pain regions in
      chronic migraine.
AB  - OBJECTIVE: Chronic migraineurs (CM) have painful intolerances to somatosensory,
      visual, olfactory, and auditory stimuli during and between migraine attacks.
      These intolerances are suggestive of atypical affective responses to potentially
      noxious stimuli. We hypothesized that atypical resting-state functional
      connectivity (rs-fc) of affective pain-processing brain regions may associate
      with these intolerances. This study compared rs-fc of affective pain-processing
      regions in CM with controls. METHODS: Twelve minutes of resting-state blood
      oxygenation level-dependent data were collected from 20 interictal adult CM and
      20 controls. Rs-fc between 5 affective regions (anterior cingulate cortex,
      right/left anterior insula, and right/left amygdala) with the rest of the brain
      was determined. Functional connections consistently differing between CM and
      controls were identified using summary analyses. Correlations between number of
      migraine years and the strengths of functional connections that consistently
      differed between CM and controls were calculated. RESULTS: Functional connections
      with affective pain regions that differed in CM and controls included regions in
      anterior insula, amygdala, pulvinar, mediodorsal thalamus, middle temporal
      cortex, and periaqueductal gray. There were significant correlations between the
      number of years with CM and functional connectivity strength between the anterior
      insula with mediodorsal thalamus and anterior insula with periaqueductal gray.
      CONCLUSION: CM is associated with interictal atypical rs-fc of affective pain
      regions with pain-facilitating and pain-inhibiting regions that participate in
      sensory-discriminative, cognitive, and integrative domains of the pain
      experience. Atypical rs-fc with affective pain regions may relate to aberrant
      affective pain processing and atypical affective responses to painful stimuli
      characteristic of CM.

PMID- 23551167
TI  - Plasmacytic post-transplant lymphoproliferative disorder: a case series of nine
      patients.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of
      organ transplantation. Although PTLD typically has a B-cell histology, an
      uncommon variant, plasmacytic PTLD can present as a monoclonal plasma cell
      proliferation similar to plasmacytomas seen in multiple myeloma. A retrospective
      analysis was performed on nine patients at our center with plasmacytic PTLD as
      characterized by plasmacytic histology with the presence of CD138 and lack of
      CD20. Of the 210 adult solid organ transplant PTLD patients diagnosed between
      1988 and 2012, 9 (4%) had a histological appearance consistent with plasmacytic
      PTLD. The median time from transplant to diagnosis was 3.7 years (range 8 months
      24 years). All patients presented with extranodal and often subcutaneous solid
      tumors. Laboratory features included elevated LDH and beta-2 microglobulin
      levels, monoclonal gammopathy, and EBV positivity of the tumor. Unlike
      conventional multiple myeloma, patients had normal calcium levels and only mild
      anemia. Six patients who have completed treatment achieved complete responses
      with radiation therapy and/or reduction in immunosuppression with two patients
      now greater than 5 years in continuous complete response. Plasmacytic PTLD,
      despite its plasmacytic histology, is responsive to conventional therapies used
      for B-cell PTLD including reduction in immunosuppression and radiation therapy.

PMID- 23551168
TI  - Patients' acceptance of medical photography in a French adult and paediatric
      dermatology department: a questionnaire survey.
AB  - BACKGROUND: Despite the increasing use of medical photography by dermatologists,
      no study on patients' perceptions of photography in dermatology has been
      performed to date. OBJECTIVES: Firstly, to evaluate patients' perceptions of
      medical photography. Secondly, to assess whether perceptions differed between
      patients in our adult department and parents accompanying a child in our
      paediatric department. METHODS: An opinion survey was conducted at the Hospital
      of Tours (France) among adult patients (adult department) and accompanying
      parents (paediatric department) by completion of a questionnaire after any
      medical photography had been performed. RESULTS: We collected 272 questionnaires
      regarding 158 adults and 114 children. A camera used only in the department, and
      storage of the images in the department's records were the most accepted
      modalities (> 90%), especially in the paediatric survey. Respondents agreed with
      the sharing of the images with other practitioners and in medical meetings (>
      85%) rather than distribution via publications (58.3%), e-mails (45.5%), health
      magazines (44.3%) and websites (32.0%). Most (78.8%) considered that the consent
      form should list all the possible uses of the images. Need for renewed consent
      for each use of the images was significantly more often expressed in the
      paediatric than the adult survey (44.5% vs. 24.5%, P = 0.001). More than 95% of
      respondents considered medical photography to be useful for improving diagnosis,
      monitoring of skin disease and aiding teaching. CONCLUSIONS: These findings could
      be used to improve practice, to increase the acceptability of medical photography
      and for devising a standardized consent form for medical practitioners performing
      medical photography.

PMID- 23551169
TI  - Should we use one-sided or two-sided P values in tests of significance?
AB  - 'P' stands for the probability, ranging in value from 0 to 1, that results from a
      test of significance. It can also be regarded as the strength of evidence against
      the statistical null hypothesis (H0). When H0 is evaluated by statistical tests
      based on distributions such as t, normal or Chi-squared, P can be derived from
      one tail of the distribution (one-sided or one-tailed P), or it can be derived
      from both tails (two-sided or two-tailed P). Distinguished statisticians, the
      authors of statistical texts, the authors of guidelines for human and animal
      experimentation and the editors of biomedical journals give confusing advice, or
      none at all, about the choice between one- and two-sided P values. Such a choice
      is available only when there are no more than two groups to be compared. I argue
      that the choice between one- and two-sided P values depends on the alternative
      hypothesis (H1), which corresponds to the scientific hypothesis. If H1 is non
      specific and merely states that the means or proportions in the two groups are
      unequal, then a two-sided P is appropriate. However, if H1 is specific and, for
      example, states than the mean or proportion of Group A is greater than that of
      Group B, then a one-sided P maybe used. The form that H1 will take if H0 is
      rejected must be stipulated a priori, before the experiment is conducted. It is
      essential that authors state whether the P values resulting from their tests of
      significance are one- or two-sided.

PMID- 23551170
TI  - Presence of oxytocin, vasopressin and atrial natriuretic peptide and their
      modification in rat hypothalamic paraventricular nucleus during resistance
      training.
AB  - Many studies have demonstrated the physiological effects of oxytocin (OT), atrial
      natriuretic peptide (ANP) and vasopressin (VP) in the homoeostasis of body fluids
      during physical exercise. However, a little information is available about the
      related immunohistochemical changes in hypothalamic magnocellular neurosecretory
      system during and after the training. The aim of the present work was to study
      the immunohistochemical changes in OT, ANP and VP levels in the hypothalamic
      paraventricular nucleus during and after resistance exercise protocol. Three
      groups of Wistar rats were trained by a rung ladder protocol for 15, 30 and 45
      days, respectively; a fourth group was left to rest for 15 days after the
      training. Finally, four sedentary groups were used as controls. The results show
      that resistance training induces a significant reduction in the percentage of OT
      positive neurons, compared with sedentary controls. In contrast, this protocol
      did not induce any change in VP levels, and ANP levels did not change
      significantly. However, VP increased after the resting period of 15 days. Our
      work shows that neurons of the paraventricular nucleus are involved in body fluid
      homoeostasis during and after resistance exercise. The functional significance of
      these changes in OT and VP levels, during and after the protocol, needs to be
      further investigated.

PMID- 23551171
TI  - Salt poisoning as a cause of morbidity and mortality in neonatal dairy calves.

PMID- 23551172
TI  - Surface-engineered growth of AgIn5S8 crystals.
AB  - The growth of semiconductor crystals and thin films plays an essential role in
      industry and academic research. Considering the environmental damage caused by
      energy consumption during their fabrication, a simpler and cheaper method is
      desired. In fact, preparing semiconductor materials at lower temperatures using
      solution chemistry has potential in this research field. We found that solution
      chemistry, the physical and chemical properties of the substrate surface, and the
      phase diagram of the multicomponent compound semiconductor have a decisive
      influence on the crystal structure of the material. In this study, we used self
      assembled monolayers (SAMs) to modify the silicon/glass substrate surface and
      effectively control the density of the functional groups and surface energy of
      the substrates. We first employed various solutions to grow
      octadecyltrichlorosilane (OTS), 3-mercaptopropyl-trimethoxysilane (MPS), and
      mixed OTS-MPS SAMs. The surface energy can be adjusted between 24.9 and 50.8
      erg/cm(2). Using metal sulfide precursors in appropriate concentrations, AgIn5S8
      crystals can be grown on the modified substrates without any post-thermal
      treatment. We can easily adjust the nucleation in order to vary the density of
      AgIn5S8 crystals. Our current process can achieve AgIn5S8 crystals of a maximum
      of 1 MUm in diameter and a minimum crystal density of approximately 0.038/MUm(2).
      One proof-of-concept experiment demonstrated that the material prepared from this
      low temperature process showed positive photocatalytic activity. This method for
      growing crystals can be applied to the green fabrication of optoelectronic
      materials.

PMID- 23551173
TI  - Green tea formulations with vitamin C and xylitol on enhanced intestinal
      transport of green tea catechins.
AB  - The effect of green tea formulated with vitamin C and xylitol on intestinal cell
      transport of gallated and nongallated catechin was studied. The transport of
      catechins from both apical to basolateral and basolateral to apical directions
      was measured. The effect of vitamin C (4, 10, 20 ppm), xylitol (11, 27.5, 55
      ppm), and combinations of both on the intestinal transport rate of catechins was
      examined. The efflux value (Pb->a/Pa->b) of (-)-epigallocatechin (EGC), (-)
      epigallocatechin gallate (EGCG), (-)-epicatechin (EC), and (-)-epicatechin
      gallate (ECG) was 0.26, 0.22, 1.22, and 0.17, respectively, indicating that EC
      appeared to be less absorbed compared with other catechins. The addition of
      xylitol (11, 27.5, 55 ppm) and vitamin C (4, 10, 20 ppm) and in combination
      enhanced transport rate of nongallated catechins such as EC and EGC. For EC,
      vitamin C was revealed to be the most effective on intestinal transport, implying
      the inhibition of the efflux transport mechanism of EC. Intestinal transport of
      gallated catechins significantly increased from catechins formulated with vitamin
      C and xylitol in a dose-dependent manner compared to the catechin-only
      formulation. Results provide a potential strategy to enhance the delivery and
      bioavailability of catechins in humans by modulating green tea formulation with
      vitamin C and xylitol.

PMID- 23551174
TI  - The complete mitochondrial genome of the dusky shark Carcharhinus obscurus.
AB  - The dusky shark Carcharhinus obscurus is economically important but vulnerable to
      overharvesting. The complete C. obscurus mitogenome was assembled from
      approximately 1 million whole genome shotgun sequences using a combination of
      reference mapping and de novo assembly (mean coverage 59x). This resulted in a
      16,706 bp double-stranded circular mitochondrial sequence. Following the
      consensus vertebrate mtDNA genome, it comprises 13 protein-coding genes, 22
      transfer RNAs, two ribosomal RNAs and has 2 non-coding areas. The A + T (56.9%)
      versus G + C (43.1%) composition confirmed an A + T bias previously noted for
      sharks. This genome is the first for the speciose Carcharhinus genus and provides
      a valuable resource for studies of shark molecular systematics, phylogeography,
      conservation genetics, and stock structure.

PMID- 23551175
TI  - Diffusion tensor imaging correlates of saccadic reaction time in children with
      fetal alcohol spectrum disorder.
AB  - BACKGROUND: Eye movement tasks provide a simple method for inferring structural
      or functional brain deficits in neurodevelopmental disorders. Oculomotor control
      is impaired in children with fetal alcohol spectrum disorder (FASD), yet the
      neuroanatomical substrates underlying this are not known. Regions of white matter
      have been shown by diffusion tensor imaging (DTI) to be different in FASD and
      thus may play a role in the delayed saccadic eye movements. The objective of this
      study was to correlate oculomotor performance with regional measures of DTI
      derived white matter anisotropy in children with FASD. METHODS: Fourteen children
      (8 to 13 years) with FASD were recruited for oculomotor assessment and DTI. Eye
      movement control was evaluated using the pro- and antisaccade tasks, in which
      subjects look at (prosaccade) or away from (antisaccade) a peripheral target.
      Saccadic reaction time (SRT; time for subjects to move their eyes after the
      target appears) and direction errors (saccades made in the incorrect direction
      relative to the instruction) were measured and correlated to fractional
      anisotropy (FA) on a voxel-by-voxel basis across the whole brain white matter.
      RESULTS: A significant positive correlation was observed between antisaccade SRT
      and FA in a large cluster containing anterior and posterior sections of the
      corpus callosum just to the right of the midline; prosaccade SRT and FA
      correlated positively in the genu of the corpus callosum and the right inferior
      longitudinal fasciculus (ILF), and correlated negatively in the left cerebellum.
      CONCLUSIONS: The negative correlation for prosaccade SRT and cerebellum
      demonstrated that individuals with slower reaction times had lower FA values
      relative to their faster responding counterparts, a finding that implicates
      cerebellar dysfunction as a significant contributor to deficits in oculomotor
      control. The higher FA in the corpus callosum and ILF corresponding to longer
      reaction times for both pro- and antisaccade was opposite to what was expected,
      but nonetheless implies that altered brain structure in these regions underlies
      deficits in oculomotor control.

PMID- 23551176
TI  - O-antigen repeat number in Salmonella enterica serovar Enteritidis is important
      for egg contamination, colonisation of the chicken reproductive tract and
      survival in egg albumen.
AB  - Salmonella enterica serovar Enteritidis is a major cause of human
      gastrointestinal disease, infection being due in large part to consumption of
      contaminated eggs. The lipopolysaccharide (LPS) of Salmonella is known to play a
      role in colonisation of the host and survival in hostile conditions including egg
      albumen. We investigated the contribution of LPS O-antigen length to colonisation
      of the reproductive tract of laying hens, contamination of eggs and survival in
      albumen. We show that expression of very-long O-antigen is essential for
      contamination of eggs, probably as a consequence of enhanced reproductive tract
      colonisation and survival in the forming egg.

PMID- 23551177
TI  - Cleavage enhancement of specific chemical bonds in DNA by cisplatin
      radiosensitization.
AB  - X-ray photoelectron spectroscopy (XPS) is harnessed as an in situ efficient
      characterization technique for monitoring chemical bond transformation in DNA and
      cisplatin-DNA complexes under synergic X-ray irradiation. By analyzing the
      variation of relative peak area of core elements of DNA as a function of
      irradiation time, we find that the most vulnerable scission sites in DNA are
      those containing phosphate and glycosidic bonds. Compared to DNA, the effective
      rate constants of the corresponding phosphodiester and glycosidic bond cleavages
      for cisplatin-DNA complexes are 1.8 and 1.9 folds larger. These damages and their
      enhancements are similar to those induced by low energy electrons (LEE).
      Consistently, the magnitude of the secondary electron distribution produced by
      the X-rays on the cisplatin-DNA complexes is considerably increased compared to
      that of pristine DNA. The data suggest that DNA radiosensization by cisplatin
      results not only from the sensitization of DNA to the action of LEE, but also
      from an increase the production of LEE at the site of binding of the cisplatin.
      The results provide new insights into the mechanisms of cisplatin-induced
      sensitization of DNA under X-ray irradiation, which could be helpful in the
      design of new cisplatin-based antitumor drugs.

PMID- 23551178
TI  - Immunohistochemical detection of sphingosine-1-phosphate receptor 1 and 5 in
      human multiple sclerosis lesions.
AB  - AIMS: Sphingosine-1-phosphate receptor (S1PR) modulating therapies are currently
      in the clinic or undergoing investigation for multiple sclerosis (MS) treatment.
      However, the expression of S1PRs is still unclear in the central nervous system
      under normal conditions and during neuroinflammation. METHODS: Using
      immunohistochemistry we examined tissues from both grey and white matter MS
      lesions for sphingosine-1-phosphate receptor 1 (S1P1 ) and 5 (S1P5 ) expression.
      Tissues from Alzheimer's disease (AD) cases were also examined. RESULTS: S1P1
      expression was restricted to astrocytes and endothelial cells in control tissues
      and a decrease in endothelial cell expression was found in white matter MS
      lesions. In grey matter MS lesions, astrocyte expression was lost in active
      lesions, while in quiescent lesions it was restored to normal expression levels.
      CNPase colocalization studies demonstrated S1P5 expression on myelin and both
      were reduced in demyelinated lesions. In AD tissues we found no difference in
      S1P1 expression. CONCLUSION: These data demonstrate a differential modulation of
      S1PRs in MS lesions, which may have an impact on S1PR-directed therapies.

PMID- 23551179
TI  - The morphology of fecal and regurgitation artifacts deposited by the blow fly
      Lucilia cuprina fed a diet of human blood.
AB  - Fly feces and regurgitation deposits may be mistaken for bloodstain patterns at a
      crime scene, potentially compromising event reconstruction and/or misdirecting
      police resources. In some instances, these artifacts contain sufficient human
      biological material to generate a full DNA profile, sometimes 2 years after
      deposition. Clearly, it is important that investigators can make the distinction
      between artifacts and bloodstains. This study examined 6645 artifacts deposited
      on a smooth, nonporous surface after Lucilia cuprina were fed human blood.
      Artifacts were also compared with bloodstains on a variety of other surfaces.
      Both similarities and differences were found between artifacts and bloodstains,
      highlighting the need for an identification system to assist personnel with
      little training in bloodstain pattern analysis. The morphology of the artifacts
      has been described so that these deposits may be more clearly distinguished from
      bloodstains, targeted by crime scene personnel as potential sources of human DNA,
      and/or identified as potential evidence contaminants. Flowcharts have been
      devised to facilitate the analysis. 

PMID- 23551180
TI  - Sensitization to Malassezia in children with atopic dermatitis combined with food
      allergy.
AB  - BACKGROUND: The yeast Malassezia belongs to our normal cutaneous flora, but is
      capable of sensitizing individuals with atopic dermatitis (AD). Our objective was
      to investigate the prevalence of sensitization to Malassezia with a 10-yr follow
      up among children suffering from AD combined with food allergy (FA) in relation
      to the extent of AD in infancy. METHODS: One hundred and eighty seven infants
      diagnosed with AD and milk/wheat allergy before 1 yr of age were included in the
      study. The area of AD was estimated from patient records of the first visit and
      measured with SCORAD at the 10-yr follow-up. Specific IgE against Malassezia was
      determined with ImmunoCAPTM at 11 yr of age. RESULTS: In infancy, 24 children
      (13%) were allergic to milk, 71 (38%) to wheat, and 92 (49%) to both milk and
      wheat, and 94 (50%) children had mild, 57 (30%) moderate and 36 (19%) severe AD.
      At the 10-yr follow-up visit, 19 (10%) of the children had ongoing milk and/or
      wheat allergy; 147 children (79%) had mild AD and 30 (16%) had SCORAD index of 0.
      Specific IgE against Malassezia mix was positive (>=0.35 kU/l) in 27% and
      specific IgE against M. sympodialis in 20% of the 187 children. The area of AD in
      infancy was associated with a greater risk of having allergen-specific IgE to
      Malassezia at the 10-yr follow-up. The risk ratio for FA was 3.11 (95% CI: 2.05
      4.72; p < 0.001) if specific IgE to Malassezia was positive. CONCLUSIONS: Infants
      with severe AD and FA seem to have a greater risk of becoming sensitized to
      Malassezia during a 10-yr follow-up.

PMID- 23551181
TI  - Large pore dermal microdialysis and liquid chromatography-tandem mass
      spectroscopy shotgun proteomic analysis: a feasibility study.
AB  - BACKGROUND/AIMS: The purpose of the present pilot study was to investigate the
      feasibility of combining large pore dermal microdialysis with shotgun proteomic
      analysis in human skin. METHODS: Dialysate was recovered from human skin by 2000
      kDa microdialysis membranes from one subject at three different phases of the
      study; trauma due to implantation of the dialysis device, a post implantation
      steady-state period, and after induction of vasodilatation and plasma
      extravasation. For shotgun proteomics, the proteins were extracted and digested
      with trypsin. Peptides were separated by capillary and nanoflow HPLC systems,
      followed by tandem mass spectrometry (MS/MS) on a Quadrupole-TOF hybrid
      instrument. The MS/MS spectra were merged and mapped to a human target protein
      database to achieve peptide identification and protein inference. RESULTS:
      Results showed variation in protein amounts and profiles for each of the
      different sampling phases. The total protein concentration was 1.7, 0.6, and 1.3
      mg/mL during the three phases, respectively. A total of 158 different proteins
      were identified. Immunoglobulins and the major classes of plasma proteins,
      including proteases, coagulation factors, apolipoproteins, albumins, and
      complement factors, make up the major load of proteins in all three test
      conditions. CONCLUSION: Shotgun proteomics allowed the identification of more
      than 150 proteins in microdialysis samples from human skin. This highlights the
      opportunities of LC-MS/MS to study the complex molecular interactions in the
      skin.

PMID- 23551182
TI  - A case of diffuse bilateral scrotal neurofibroma in a rabbit.
AB  - This report details a rare case of diffuse bilateral scrotal neurofibroma
      complicated by hindlimb paralysis in a rabbit. The animal was evaluated for
      unusual bilateral scrotal enlargement. After physical examination, ultrasound
      scan, radiography, computed tomography and laparoscopy, surgical exploration of
      the scrotum was undertaken. A homogeneous rubbery firm mass was revealed in
      contact with the subcutaneous tissue expanding to the entire scrotum without
      involving the testicles. The mass was excised and diagnosed as diffuse scrotal
      neurofibroma based on histological and immunohistochemical findings (S-100
      antibody positive). Over the following month, progressive neurological signs
      (faecal incontinence, flaccid bladder and hindlimb paralysis) were observed.
      After excluding central nervous system infection with Encephalitozoon cuniculi,
      expansion of the neurofibroma to the vertebral canal causing compression of the
      spinal cord was suspected, although not histopathologically verified. 

PMID- 23551183
TI  - Long-term growth of children with autoantibody-mediated congenital heart block.
AB  - AIM: To analyse growth of children with and without congenital heart block (CHB)
      born to anti-Ro/SSA positive mothers from birth to 18 years of age, using a
      population-based cohort of Swedish CHB patients. METHODS: Medical records for
      siblings with (n = 72) and without (n = 60) CHB born 1973-2009 to anti-Ro/SSA
      positive mothers were retrieved from child healthcare centres and school health
      services and used to extract data on growth from birth to 18 years. RESULTS:
      Compared with reference standards, children with CHB were retarded in weight by
      0.75-1.0 SD from birth to 2-3 years of age. Thereafter, the CHB children started
      to catch up, reaching the reference standards at 9-11 years of age. Pacemaker
      treatment was not correlated with the catch-up in growth. Individuals with CHB
      were retarded in both weight and height from birth to 9-11 years of age when
      compared to siblings without CHB, who did not demonstrate restriction in these
      measurements. CONCLUSION: Presence of CHB is a more important predictor of growth
      restriction than maternal rheumatic disease and foetal anti-Ro/SSA exposure. The
      restriction persists for several years after birth, despite pacemaker treatment,
      which highlights the importance of follow-up of children with CHB regarding
      nutrition and growth.

PMID- 23551184
TI  - Intracellular targeting and pharmacological activity of the superoxide dismutase
      mimics MnTE-2-PyP5+ and MnTnHex-2-PyP5+ regulated by their porphyrin ring
      substituents.
AB  - Manganese porphyrin-based drugs are potent mimics of the enzyme superoxide
      dismutase. They exert remarkable efficacy in disease models and are entering
      clinical trials. Two lead compounds, MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+), have
      similar catalytic rates, but differ in their alkyl chain substituents (ethyl vs n
      hexyl). Herein we demonstrate that these changes in ring substitution impact upon
      drug intracellular distribution and pharmacological mechanism, with MnTnHex-2
      PyP(5+) superior in augmenting menadione toxicity. These findings establish that
      both catalytic activity and intracellular distribution determine drug action.

PMID- 23551185
TI  - The innovation journey of genomics and asthma research.
AB  - This article concerns the transformative potential of medical genomics for common
      disease research. We analysed 13 review articles in asthma research in the period
      1999 to 2008. Our aim was to understand how genomics has emerged in this research
      field, and the attendant changes. Motivated by Lippman's geneticisation thesis,
      we use the concept of an 'innovation journey' to trace how expectations of
      improved understanding, prevention, diagnosis and treatment structure a dynamic
      co-evolutionary process through which a genome-based discourse emerges. We show
      how the asthma researchers involved continuously struggle to define their
      contribution to asthma research, as well as to clinical practice. Along the way,
      the researchers propose changes to both the definition and the aetiological model
      of asthma, thus highlighting gene-gene and gene-environment interactions. It is,
      however, difficult to characterise this discourse as one of geneticisation. With
      increasing attention being given to epigenetics, metabolomics, proteomics and
      systems biology, the emerging picture suggests an important, but much less
      deterministic, role for genes.

PMID- 23551186
TI  - What predicts enduring intractability in children who appear medically
      intractable in the first 2 years after diagnosis?
AB  - PURPOSE: In a population-based retrospective cohort of children with newly
      diagnosed epilepsy, to determine (1) what proportion meet criteria for early
      medical intractability, and (2) predictors of enduring intractability. METHODS:
      Children with newly diagnosed epilepsy between 1980 and 2009 while resident in
      Olmsted County, MN, and followed >36 months, were stratified into groups based on
      both early medical intractability ("apparent" medical intractability in the first
      2 years) and enduring intractability (persisting intractability at final follow
      up or having undergone surgery for intractable epilepsy), and variables
      predicting these outcomes were evaluated. KEY FINDINGS: Three hundred eighty-one
      children were included, representing 81% of our cohort with newly diagnosed
      epilepsy. Seventy five (19.7%) had early medical intractability, and predictors
      of this outcome on multivariable analysis were neuroimaging abnormality (risk
      ratio, 2.70; p = 0.0004), abnormal neurologic examination at diagnosis (risk
      ratio, 1.87; p = 0.015), and mode of onset (association was significant for focal
      vs. generalized onset [risk ratio, 0.25; p < 0.0001] but not unknown vs.
      generalized onset [p = 0.065]). After a median follow-up of 11.7 years, 49%
      remained intractable, 8% had rare seizures (<= every 6 months), and the remainder
      were seizure-free. The only factor predicting enduring intractability on
      multivariable analysis was neuroimaging abnormality (risk ratio, 7.0; p =
      0.0006). SIGNIFICANCE: Although a significant minority of children with early
      medical intractability ultimately achieved seizure control without surgery, those
      with an abnormal imaging study did poorly. For this subgroup, early surgical
      intervention is strongly advised to limit comorbidities of ongoing, intractable
      seizures. Conversely, a cautious approach is suggested for those with normal
      imaging, as most will remit with time.

PMID- 23551187
TI  - Cone survival and preservation of visual acuity in an animal model of retinal
      degeneration.
AB  - The prevention of cone loss during retinal degeneration is a major goal of most
      therapeutic strategies in retinal degenerative diseases. An intriguing issue in
      the current research in this field is to understand why a genetic mutation that
      affects rods eventually leads to cone death. The main objective of the present
      study was to investigate to what extent rescuing rods from degeneration affects
      the survival of cones and prevents functional impairment of the visual
      performance. To this purpose, we compared rod and cone viabilities by both ex
      vivo and in vivo determinations in the rd10 mutant mouse, a validated model of
      human retinitis pigmentosa. The ex vivo experiments included morphological and
      biochemical tests, whereas in vivo studies compared the rod-mediated scotopic
      with the cone-mediated photopic electroretinogram. We also determined the overall
      visual performance by behaviorally testing the visual acuity (VA). The
      electroretinogram measurements showed that the kinetics of the photopic response
      in rd10 mice was slowed down with respect to the age-paired wild-type at a very
      early stage of the disease, when rods were still present and responsive. We then
      tested cone viability and function under a pharmacological scheme previously
      shown to prolong rod survival. The treatment consisted of eye drop administration
      of myriocin, an inhibitor of the biosynthesis of ceramide, a powerful
      proapoptotic messenger. The results of biochemical, morphological and functional
      assays converged to show that, in treated rd10 mice cone photoreceptors, the
      inner retina and overall visual performance were preserved well after rod death.

PMID- 23551188
TI  - Liver transplantation using grafts of living donors with isolated unconjugated
      hyperbilirubinemia: a matched case-control study.
AB  - Unconjugated bilirubin has shown both cytotoxic and cytoprotective effects,
      acting as either an oxidant or an antioxidant. Elevated unconjugated bilirubin
      with otherwise normal, so-called isolated unconjugated hyperbilirubinemia (IUHB),
      is encountered frequently in living liver donor evaluation. However, the
      significance of IUHB on transplantation-related outcomes has not been clarified
      in donors and recipients. Forty-six living donors with IUHB were matched 1:1 with
      the control donors and 43 recipients who received grafts from donors with IUHB
      were matched 1:1 with the control recipients. Matched variables included
      donor/recipient age, residual liver volume, steatosis, cold ischemic time, graft
      versus recipient weight ratio, the MELD score and others. Donors in the control
      and IUHB group were comparable regarding the maximum postoperative transaminase
      concentrations, postoperative complications, and hospital stay. Recipients in the
      control and IUHB group were comparable regarding primary graft dysfunction, major
      postoperative complications, long-term ICU/hospital stay, 1-year mortality, and
      rejection rate, as well as recipient/graft survival rates. Recipients'
      unconjugated bilirubin concentration at 3 years after transplantation was higher
      in IUHB group with otherwise comparable liver function. It was concluded that
      living donor liver transplantation is safe for donors with IUHB and their
      recipients.

PMID- 23551189
TI  - Angiogenesis and collagen type IV expression in different endothelial cell
      culture systems.
AB  - In vitro angiogenesis assays constitute an important tool for studying the
      mechanisms of angiogenesis and for identification of pro- and anti-angiogenic
      substances. Therefore, endothelial cell and media systems used for in vitro
      angiogenesis assays are required to mimic the angiogenic process in vivo
      including endothelial capability to express collagen type IV as a component of
      the basement membrane. In this study, the expression of collagen type IV and its
      alpha chains (alpha1-6) was investigated in different endothelial cell culture
      systems in vitro qualitatively and quantitatively. These systems included four
      different batches of microvascular endothelial cells derived from the human skin,
      heart and lung, from which only two batches were found to be angiogenic and two
      batches were classified as non-angiogenic. Distribution of the transcripts of the
      alpha chains of collagen type IV was similar in all cell and media systems
      investigated. However, secretion and deposition of a stable extracellular network
      of collagen type IV could only be observed in the angiogenic cultures. In
      conclusion, the consecutive steps of the angiogenic cascade in vivo as well as in
      vitro depend on an increasing secretion and subsequent extracellular deposition
      of collagen type IV. 

PMID- 23551190
TI  - Caries prevalence (ICDAS) in 12-year-olds from low caries prevalence areas and
      association with independent variables.
AB  - BACKGROUND: In areas with low caries prevalence, indices are needed for caries
      detection, which can also be used to identify initial lesions. AIM: The aim of
      this study was to assess the caries prevalence among 12-year-olds using ICDAS
      criteria and to investigate the influence of independent variables on the
      findings. DESIGN: The study was conducted in two regions of Germany. In Region 1,
      children received regular school-based prophylaxis, including fluoride varnish
      2*/yr. In Region 2, there was no use of fluoride varnish in schools. Information
      on different factors influencing the outcome variable of caries experience was
      collected using structured questionnaires. DF-S values were calculated at
      different ICDAS cut-off points. To compare the mean caries scores of the
      subgroups, nonparametric tests were performed. Variables associated with caries
      were included in a binary logistic regression analysis. RESULTS: At D(1-6) FS and
      D(1+2) FS level, the differences between the regions were statistically
      significant (P = 0.005 and P = 0.01, respectively). Regression analysis
      identified the variables 'use of fluoridated toothpaste', 'fissure sealants', and
      'ethnic origin' as factors significant to the prevention of caries at various
      stages. CONCLUSION: In a population with low caries prevalence, significant
      differences between subgroups could only be found when initial lesions were
      included.

PMID- 23551191
TI  - Burden of disease due to cutaneous melanoma has increased in the Netherlands
      since 1991.
AB  - BACKGROUND: The burden of disease, describing loss of health and death due to a
      disease, has not been fully studied for melanoma in the general population over
      time. OBJECTIVES: To determine the burden of disease due to melanoma in the
      Netherlands. METHODS: Age- and sex-specific incidence data from all patients with
      melanoma in the Netherlands between 1991 and 2010 were obtained from the
      Netherlands Cancer Registry. Melanoma-specific mortality and life expectancy data
      were obtained from Statistics Netherlands. Melanoma duration was calculated using
      the DISMOD software from the World Health Organization. The years of life lived
      with disability (YLD) and years of life lost (YLL) due to melanoma were
      calculated using Dutch disability weights, incidence and mortality of melanoma,
      and the life expectancy from the general population. The number of disability
      adjusted life-years (DALYs) was estimated by adding YLD and YLL. RESULTS: The
      world-standardized incidence rates of melanoma have more than doubled for both
      men (7.1 per 100 000 inhabitants in 1991 to 17.0 in 2010) and women (9.4 per 100
      000 inhabitants in 1991 to 19.8 in 2010). Likewise, the burden of melanoma to
      society has increased rapidly. The YLD for men increased from 4795 (1991-4) to 12
      441 (2007-10), and for women from 7513 (1991-4) to 16 544 (2007-10). In 2007-10
      the total YLL due to melanoma was 30 651 for men and 26 244 for women compared
      with 17 238 and 16 900, respectively, in 1991-4. The DALYs increased by 96% for
      men, from 22 033 (1991-4) to 43 092 (2007-10), and by 75% for women, from 24 413
      (1991-4) to 42 788 (2007-10). CONCLUSIONS: Melanoma is becoming a great burden to
      Dutch society.

PMID- 23551192
TI  - Incidental white matter lesions in children presenting with headache.
AB  - AIM: We aimed to describe the prevalence and significance of white matter lesions
      detected on magnetic resonance imaging (MRI) in children with headache. MATERIAL
      AND METHODS: Children who were admitted with the complaint of headache and had
      neuroimaging between December 2007 and June 2012 were included in the study. The
      clinical and neuroimaging data of the patients were retrospectively evaluated.
      MRI results of the patients were documented in detail. The patients with non
      specific white matter lesions were called for a control visit, and current status
      of headache and neurological findings were determined. RESULTS: A total of 941
      patients were included in the study. Sixty-one percent of the patients received
      cranial neuroimaging. 8.2% had only cranial computed tomography (CT), 7.5% had
      cranial CT and cranial MRI, and 84.3% had only cranial MRI. 22.1% of the patients
      had abnormal cranial MRI findings. The rate of incidental non-specific white
      matter changes detected in our study group was 23/527 (4.4%). Among the 23
      patients, 12 (52.2%) were male and 11 (47.8%) were female. Fourteen (60.9%) had
      migraine without aura, 8 (34.8%) had tension-type headache, and 1 (4.3%) had
      migraine with aura. Mean age of patients at the time of imaging was 12.1 +/- 3.4
      years (range 4.0-16.0 years). All patients with non-specific white matter changes
      on MRI showed normal psychomotor development, and there was no history of
      seizures or head trauma. The physical and neurological examinations of all
      patients were normal. The mean clinical follow-up period of the patients was 16.8
      +/- 17.3 months (range 6-80 months). No patients showed neurological
      deterioration during the follow up. The white matter lesions were supratentorial
      in all patients. The mean size of the lesions was 5.1 +/- 4.5 mm (minimum, 2 mm;
      maximum, 24 mm). Repeated radiological evaluations were performed in 11 (47.8%)
      of the patients. No new white matter lesions were detected in control MRI during
      follow up. CONCLUSION: Non-specific incidental white matter changes may be seen
      in children with headache. For normal clinical follow up, in the absence of
      evident benefits from repeated imaging studies, we suggest that repeated imaging
      studies are not warranted in every patient and should be tailored according to
      clinical course.

PMID- 23551193
TI  - Conformational control in [22]- and [24]pentaphyrins(1.1.1.1.1) by meso
      substituents and their N-fusion reaction.
AB  - meso-Substituted pentaphyrins(1.1.1.1.1) were unexpectedly isolated as N-fused
      species under Rothemund-type conditions. The reaction mechanism is unknown at
      present, but the first example of a nonfused [22]pentaphyrin was reported in
      2012. Here, the conformational preferences and N-fusion reaction of [22]- and
      [24]pentaphyrins have been investigated using density functional calculations,
      together with their aromaticity-molecular topology relationships. Two global
      minima are found for the unsubstituted [22]pentaphyrin corresponding to T0 and
      T0(4,D) Huckel structures. Mobius transition states are located in the
      interconversion pathways with activation barriers of 27 kcal mol(-1). Conversely,
      [24]pentaphyrin is able to switch between Huckel and Mobius conformers with very
      low activation barriers. However, nonfused [24]pentaphyrins are unstable and
      spontaneously undergo an N-fusion reaction driven by the strain release. On the
      contrary, nonfused [22]pentaphyrins could be isolated if a T0(4,D) conformation
      is adopted. Importantly, conformational control of pentaphyrins can be achieved
      by meso-substituents. Two stable conformations (T0(4,D) and T0(A,D)) are found
      for the nonfused [22]pentaphyrin, which are delicately balanced by the number of
      substituents. The T0(A,D) conformation is preferred by fully meso-aryl
      pentaphyrins, which is converted to the N-fused species. Interestingly, the
      removal of one aryl group prevents the N-fusion reaction, providing stable
      aromatic nonfused [22]pentaphyrins in excellent agreement with the experimental
      results.

PMID- 23551195
TI  - Thermal and pH responsive polymer-tethered multifunctional magnetic nanoparticles
      for targeted delivery of anticancer drug.
AB  - Targeted and efficient delivery of therapeutics to tumor cells is one of the key
      issues in cancer therapy. In the present work, we report a temperature and pH
      dual responsive core-shell nanoparticles comprising smart polymer shell coated on
      magnetic nanoparticles as an anticancer drug carrier and cancer cell-specific
      targeting agent. Magnetite nanoparticles (MNPs), prepared by a simple
      coprecipitation method, was surface modified by introducing amine groups using 3
      aminopropyltriethoxysilane. Dual-responsive poly(N-isopropylacrylamide)-block
      poly(acrylic acid) copolymer, synthesized by reversible addition-fragmentation
      chain transfer (RAFT) polymerization, was then attached to the amine
      functionalized MNPs via EDC/NHS method. Further, to accomplish cancer-specific
      targeting properties, folic acid was tethered to the surface of the
      nanoparticles. Thereafter, rhodamine B isothiocyanate was conjugated to endow
      fluorescent property to the MNPs required for cellular imaging applications. The
      nanoparticles were characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM), selected area electron diffraction (SAED), field
      emission scanning electron microscopy (FESEM), energy-dispersive X-ray
      spectroscopy (EDX), thermogravimetric analysis (TGA), zeta potential, vibrating
      sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS) measurements,
      and FTIR, UV-vis spectral analysis. Doxorubicin (DOX), an anticancer drug used
      for the present study, was loaded into the nanoparticles and its release behavior
      was subsequently studied. Result showed a sustained release of DOX preferentially
      at the desired lysosomal pH and temperature condition. The biological activity of
      the DOX-loaded MNPs was studied by MTT assay, fluorescence microscopy, and
      apoptosis. Intracellular-uptake studies revealed preferential uptake of these
      nanoparticles into cancer cells (HeLa cells) compared to normal fibroblast cells
      (L929 cells). The in vitro apoptosis study revealed that the DOX-loaded
      nanoparticles caused significant death to the HeLa cells. These nanoparticles
      were capable of target specific release of the loaded drug in response to pH and
      temperature and hence may serve as a potential drug carrier for in vivo
      applications.

PMID- 23551196
TI  - Downhill varices secondary to HeRO graft-related SVC syndrome.
AB  - Tunneled hemodialysis catheters are well-documented causes of benign central vein
      stenosis, which can be associated with proximal or downhill esophageal varices
      due to shunting of blood flow from the upper portion of the body through the
      esophageal venous plexuses. A majority of these cases remain asymptomatic. As a
      result, studies are largely limited to symptomatic patients, with incidence rates
      ranging from 16% to 29%. Recently, Hemodialysis Reliable Outflow (HeRO) graft has
      been introduced as an effective alternate hemodialysis access in catheter
      dependent patients, especially in the presence of significant central venous
      occlusion. It differs from a conventional arteriovenous graft (AVG) by the fact
      that its venous outflow end is in the right atrium via one of the central veins,
      bypassing any significant occlusion upstream. Lower intervention rates and
      reduced incidence of bacteremia make it comparable to conventional tunneled
      catheters. However, the incidence of central vein occlusion and associated
      complications with HeRO grafts is unknown. We present the first case of
      gastrointestinal bleeding from downhill esophageal varices secondary to HeRO
      graft-related SVC occlusion.

PMID- 23551198
TI  - Remediation of environmental pollution by substituting poly(vinyl alcohol) with
      biodegradable warp size from wheat gluten.
AB  - We report the development of wheat gluten as an environmentally friendly sizing
      agent that can replace poly(vinyl alcohol) (PVA) and make the textile industry
      more environmentally friendly. Wheat gluten applied onto polyester/cotton (P/C)
      and polyester as warp sizing agent provided sizing performance and
      biodegradability in activated sludge necessary to substitute poly(vinyl alcohol)
      (PVA). PVA is one of the most widely used sizing agents and provides excellent
      sizing performance to synthetic fibers and their blends but is expensive and
      difficult to degrade in textile wastewater treatment plants. Although
      considerable efforts have been made to replace PVA, it has not been possible to
      develop a warp sizing chemical that can match the sizing performance of PVA and
      at the same time be cost-effective and biodegrade in effluent treatment plants.
      At similar % add-on, wheat gluten provided similar cohesion to P/C but much
      higher abrasion resistance to polyester fabrics compared to PVA. With a
      biochemical oxygen demand (BOD) to chemical oxygen demand (COD) ratio of 0.7
      compared to 0.01 for PVA, wheat gluten was readily degradable in activated
      sludge. Wheat gluten has the ability to replace PVA for textile warp sizing
      applications.

PMID- 23551197
TI  - An exploratory microdialysis study investigating the effect of repeated
      application of a diclofenac epolamine medicated plaster on prostaglandin
      concentrations in skeletal muscle after standardized physical exercise.
AB  - AIM: Muscle injuries and extensive exercise are associated with cyclo-oxygenase
      dependent formation of inflammatory prostaglandins. Since the effect of topical
      administration of non-steroidal anti-inflammatory drugs (NSAIDs) on local cyclo
      oxygenase is unknown, the present exploratory, open label, non-randomized study
      set out to measure exercise induced release of prostaglandins before and after
      epicutaneous administration of diclofenac. METHODS: Microdialysis was used to
      determine the local interstitial concentration of PGE2 and 8-iso-PGF2alpha as
      well as diclofenac concentrations in the vastus lateralis under rest, dynamic
      exercise and during recovery in 12 healthy subjects at baseline and after a
      treatment phase applying a total of seven plasters medicated with 180 mg of
      diclofenac epolamine over 4 days. RESULTS: At baseline PGE2 concentrations were
      1169 +/- 780 pg ml(-1) at rest and 1287 +/- 459 pg ml(-1) during dynamic exercise
      and increased to 2005 +/- 1126 pg ml(-1) during recovery. After treatment average
      PGE2 concentrations were 997 +/- 588 pg ml(-1) at rest and 1339 +/- 892 pg ml(-1)
      during exercise. In contrast with the baseline phase no increase in PGE2
      concentrations was recorded during the recovery period after treatment (PGE2 1134
      +/- 874 pg ml(-1)). 8-iso-PGF2alpha was neither affected by exercise nor by
      treatment with diclofenac. Local and systemic concentrations of diclofenac were
      highly variable but comparable with previous clinical pharmacokinetic studies.
      CONCLUSIONS: We can hypothesize an effect of topical diclofenac epolamine plaster
      on limiting the increase of local concentrations of the pro-inflammatory
      prostaglandin PGE2 induced in the muscle of healthy human subjects following
      standardized physical exercise. No effect of diclofenac treatment on 8-iso
      PGF2alpha concentrations was observed, mainly since isoprostane is produced by a
      free radical-catalyzed lipid peroxidation mechanism independent of cyclo
      oxygenases.

PMID- 23551199
TI  - Aerobic exercise moderates the effect of heavy alcohol consumption on white
      matter damage.
AB  - BACKGROUND: Chronic alcohol abuse is related to numerous deleterious
      neurobiological consequences, including loss of gray matter, damage to white
      matter (WM), and impairment of cognitive and motor functions. Aerobic exercise
      has been demonstrated to slow cognitive decline and decrease the negative neural
      changes resulting from normal aging and from several diseases. It is possible
      that exercise may also prevent or repair alcohol-related neurological damage.
      This study tested the hypothesis that aerobic exercise protects WM in anterior
      and dorsal areas of the brain from damage related to heavy alcohol use. METHODS:
      Sixty individuals underwent a diffusion tensor imaging session and completed
      measures of alcohol consumption, loss of control over drinking, and aerobic
      exercise participation. Analyses examined the relationship of exercise, alcohol,
      and their interaction to fractional anisotropy (FA) in the superior longitudinal
      fasciculus (SLF), external capsule (EC), superior and anterior corona radiata,
      and fornix. The relationship of aerobic exercise and alcohol consumption to self
      reported loss of control over drinking were also examined. RESULTS: A significant
      interaction was observed between alcohol consumption and aerobic exercise
      participation on FA in the SLF and EC. In the models examining loss of control
      over drinking, a significant interaction between aerobic exercise and alcohol
      consumption was observed, such that alcohol consumption was associated with loss
      of control more strongly for low exercisers than high exercisers. CONCLUSIONS:
      These results indicate that the association between heavy alcohol consumption and
      WM damage in the EC and SLF and the association between alcohol consumption and
      loss of control over drinking are greater among individuals who do not exercise
      regularly. These results are consistent with the notion that exercise may protect
      WM integrity from alcohol-related damage.

PMID- 23551200
TI  - Comparison between supercritical CO2 extraction and hydrodistillation for two
      species of eucalyptus: yield, chemical composition, and antioxidant activity.
AB  - In this work, 2 Eucalyptus species extracts (Eucalyptus cinerea and Eucalyptus
      camaldulensis) were prepared by hydrodistillation (HD) and supercritical carbon
      dioxide extraction (SCE) techniques. The best yields of E. cinerea and E.
      camaldulensis (27.5 and 8.8 g/kg, respectively) were obtained using SCE at 90
      bar, 40  degrees C compared to HD (23 and 6.2 g/kg, respectively). Extracts were
      quantified by gas chromatography-flame ionization detection and identified by gas
      chromatography-mass spectrometry. 1,8-cineole and p-menth-1-en-8-ol were the
      major compounds of E. cinerea essential oil obtained by HD (64.89% and 8.15%,
      respectively) or by SCE (16.1% and 31.87%, respectively). Whereas, in case of E.
      camaldulensis, 1,8-cineole (45.71%) and p-cymene (17.14%) were the major
      compounds obtained by HD, and 8,14-cedranoxide (43.79%) and elemol (6.3%) by SCE.
      Their antioxidant activity was assessed using 2 methods: 2,2-azino-di-3
      ethylbenzothialozine-sulphonic acid radical cation (ABTS(*+) ) and 2,2-diphenyl-1
      picrylhydrazyl radical (DPPH(*) ). In the SCE extracts from both E. cinerea and
      E. camaldulensis, a promising radical scavenging activity was observed with
      ABTS(*+) , (65 and 128 mg/L, respectively). The total phenolics composition of
      the extracts was measured and the range was 2 to 60 mg of gallic acid
      equivalent/g dry plant material. The SCE method was superior to HD, regarding
      shorter extraction times (30 min for SCE compared with 4 h for HD), a low
      environmental impact, allows production of nondegraded compounds and being part
      of green chemistry.

PMID- 23551194
TI  - Molecular testing guideline for selection of lung cancer patients for EGFR and
      ALK tyrosine kinase inhibitors: guideline from the College of American
      Pathologists, International Association for the Study of Lung Cancer, and
      Association for Molecular Pathology.
AB  - OBJECTIVE: To establish evidence-based recommendations for the molecular analysis
      of lung cancers that are required to guide EGFR- and ALK-directed therapies,
      addressing which patients and samples should be tested, and when and how testing
      should be performed. PARTICIPANTS: Three cochairs without conflicts of interest
      were selected, one from each of the 3 sponsoring professional societies: College
      of American Pathologists, International Association for the Study of Lung Cancer,
      and Association for Molecular Pathology. Writing and advisory panels were
      constituted from additional experts from these societies. EVIDENCE: Three
      unbiased literature searches of electronic databases were performed to capture
      articles published from January 2004 through February 2012, yielding 1533
      articles whose abstracts were screened to identify 521 pertinent articles that
      were then reviewed in detail for their relevance to the recommendations. Evidence
      was formally graded for each recommendation. CONSENSUS PROCESS: Initial
      recommendations were formulated by the cochairs and panel members at a public
      meeting. Each guideline section was assigned to at least 2 panelists. Drafts were
      circulated to the writing panel (version 1), advisory panel (version 2), and the
      public (version 3) before submission (version 4). CONCLUSIONS: The 37 guideline
      items address 14 subjects, including 15 recommendations (evidence grade A/B). The
      major recommendations are to use testing for EGFR mutations and ALK fusions to
      guide patient selection for therapy with an epidermal growth factor receptor
      (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all
      patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking
      history, or other clinical risk factors, and to prioritize EGFR and ALK testing
      over other molecular predictive tests. As scientific discoveries and clinical
      practice outpace the completion of randomized clinical trials, evidence-based
      guidelines developed by expert practitioners are vital for communicating emerging
      clinical standards. Already, new treatments targeting genetic alterations in
      other, less common driver oncogenes are being evaluated in lung cancer, and
      testing for these may be addressed in future versions of these guidelines.

PMID- 23551201
TI  - Ex vivo absorption of thymol and thymol-beta-D-glucopyranoside in piglet everted
      jejunal segments.
AB  - Food-producing animals are reservoirs of Campylobacter, a leading bacterial cause
      of human foodborne illness. The natural product thymol can reduce the
      survivability of Campylobacter, but its rapid absorption in the proximal
      gastrointestinal tract may preclude its use as a feed additive to reduce
      intestinal colonization of these pathogens. This work examined the ex vivo
      absorption of thymol and thymol-beta-d-glucopyranoside in everted porcine jejunal
      segments, as the latter was hypothesized to be more resistant to absorption. A
      modified gas chromatography and extraction method was developed to determine 1.0
      500 mg/L thymol. From 1 and 3 mM solutions, 0.293 +/- 0.04 and 0.898 +/- 0.212 mM
      thymol, respectively, p = 0.0347, were absorbed, and 0.125 +/- 0.041 and 0.317 +/
      0.143 mM thymol-beta-d-glucopyranoside, respectively, p = 0.0892, were absorbed.
      Results indicate that thymol-beta-d-glucopyranoside was absorbed 2.3 to 2.8 times
      less effectively than thymol, thus providing evidence that thymol-beta-d
      glucopyranoside may potentially be used as a feed additive to transport thymol to
      the piglet lower gut.

PMID- 23551202
TI  - Isolation of proteorhodopsin-bearing bacterium JL-3 from fresh water and
      characterization of the proteorhodopsin.
AB  - Proteorhodopsins (PRs), light-driven proton pumps, constitute the largest family
      of the microbial rhodopsins. PRs are widely distributed in the oceanic
      environment and freshwater, but no bacteria with PRs have been isolated from
      freshwater so far. To facilitate isolation of the bacteria with PR genes, we
      constructed a vector system that can be used to clone potential PR genes and
      render color changes when overexpressed in Escherichia coli. Using this method,
      we successfully isolated a strain with PR gene from freshwater and identified it
      as Exiguobacterium sp. JL-3. The full length PR gene was then cloned using the
      SEFA PCR method. Protein sequence alignment showed that JL-3_PR shares high
      sequence identity (84-89%) with the PRs from Exiguobacterium strains, but low
      sequence identity (< 38%) with other PRs. Surprisingly, we could not detect any
      proton-pumping activity in the native JL-3 cells and protoplasts, but the
      recombinant JL-3_PR do pump protons when overexpressed in E. coli. Sequence
      analysis further revealed that the PRs from Exiguobacterium had an unusual lysine
      as the proton donor instead of the typical acidic residue. These data suggest
      that JL-3_PR is a sensory PR rather than a proton pump.

PMID- 23551203
TI  - Adolescent inhalant use and executive cognitive functioning.
AB  - BACKGROUND: This study investigates the association between inhalant use and
      executive cognitive functioning (ECF) and processing speed (PS) in 754
      adjudicated poly-substance users on a series of neuropsychological tests. Poly
      substance users who used inhalants (PSI = 262) and poly-substance users who did
      not use inhalants (PSO = 492) neuropsychological tests scores were compared.
      Hispanic Americans comprised 72% of the participants; European Americans, African
      Americans and Asian Americans comprised 28% of the participants. METHODS:
      Standardized neuropsychological tests were used to assess ECF and PS.
      Psychosocial and substance abuse standardized surveys were used to assess drug
      use severity and psychosocial problems associated with substance use. RESULTS:
      Multiple Analysis of Covariance shows that PSI users who used inhalants performed
      worse on ECF and PS measures in comparison to non-inhalant poly-substance users
      (PSO). PSI users were younger, used more drugs and had more psychiatric
      admissions than PSO users. CONCLUSION: PSI users initiate substances at a younger
      age and experienced more ECF and PS deficits, and behavioural problems in
      comparison to PSO users. The results of this study suggest that PS has direct
      effect on ECF and psychosocial outcomes in PSI users.

PMID- 23551204
TI  - A strategy to explore stable and metastable ordered phases of block copolymers.
AB  - Block copolymers with their rich phase behavior and ordering transitions have
      become a paradigm for the study of structured soft materials. A major challenge
      in the study of the phase behavior of block copolymers is to obtain different
      stable and metastable phases of the system. A strategy to discover complex
      ordered phases of block copolymers within the self-consistent field theory
      framework is developed by a combination of fast algorithms and novel
      initialization procedures. This strategy allows the generation of a large number
      of candidate structures, which can then be used to construct phase diagrams.
      Application of the strategy is illustrated using ABC star triblock copolymers as
      an example. A large number of candidate structures, including many three
      dimensionally ordered phases, of the system are obtained and categorized. A phase
      diagram is constructed for symmetrically interacting ABC star triblock
      copolymers.

PMID- 23551205
TI  - The interest of postmortem bacteriology in putrefied bodies.
AB  - A 27-year-old man was found dead in an advanced decomposition stage at home. On
      external examination, his body showed petechial hemorrhages of the skin. At
      autopsy, petechial hemorrhages of the epicardium were found, but no sign of
      meningitis was detected. Toxicological investigations remained negative.
      Bacteriological conventional analyses showed no significant result. Neisseria
      meningitidis serogroup B was finally isolated on cerebrospinal fluid by a
      specific real-time polymerase chain reaction. To our knowledge, there are no
      available data about the postmortem diagnosis of an infectious cause of death in
      a decomposed corpse. In such situations, the polymicrobial overgrowth usually
      hampers the interpretation of bacteriological conventional methods and questions
      their diagnostic value. Such molecular bacteriological approaches appear to
      constitute an important diagnostic tool for forensic scientists and should be
      widely processed in case of suspected infectious death or sudden death whatever
      the postmortem interval. 

PMID- 23551206
TI  - Top-down structural analysis of an intact monoclonal antibody by electron capture
      dissociation-Fourier transform ion cyclotron resonance-mass spectrometry.
AB  - Top-down electron capture dissociation (ECD) Fourier transform ion cyclotron
      resonance (FTICR) mass spectrometry was performed for structural analysis of an
      intact monoclonal antibody (IgG1kappa (kappa) isotype, ~148 kDa). Simultaneous
      ECD for all charge states (42+ to 58+) generates more extensive cleavages than
      ECD for an isolated single charge state. The cleavages are mainly localized in
      the variable domains of both heavy and light chains, the respective regions
      between the variable and constant domains in both chains, the region between
      heavy-chain constant domains CH2 and CH3, and the disulfide bond (S-S)-linked
      heavy-chain constant domain CH3. The light chain yields mainly N-terminal
      fragment ions due to the protection of the interchain disulfide bond between
      light and heavy chain, and limited cleavage sites are observed in the variable
      domains for each chain, where the S-S spans the polypeptide backbone. Only a few
      cleavages in the S-S-linked light-chain constant domain, hinge region, and heavy
      chain constant domains CH1 and CH2 are observed, leaving glycosylation
      uncharacterized. Top-down ECD with a custom-built 9.4 T FTICR mass spectrometer
      provides more extensive sequence coverage for structural characterization of
      IgG1kappa than does top-down collision-induced dissociation (CID) and electron
      transfer dissociation (ETD) with hybrid quadrupole time-of-flight instruments and
      comparable sequence coverage for top-down ETD with orbitrap mass analyzers.

PMID- 23551207
TI  - Duplicated ectopic ureter in a nine-year-old Labrador.
AB  - A nine-year-old male neutered Labrador retriever presented with a history of
      chronic urinary tract infections and occasional dribbling of urine. Abdominal
      ultrasound showed changes suggestive of a left ectopic ureter. A pneumocystogram
      revealed an air-filled distended tubular and tortuous structure extending from
      the region of the prostatic urethra to the left kidney, consistent with an
      ectopic ureter. Intravenous urography depicted the presence of an additional left
      ureter with only slightly larger diameter than the right and with normal
      insertion in the bladder neck. A duplicated ectopic left ureter was suspected and
      confirmed during surgery. To the authors' knowledge, this is the first
      description of a duplicated ectopic ureter in the canine species. The combination
      of ultrasound and contrast radiography was important to reach the diagnosis. 

PMID- 23551208
TI  - Intra- and inter-rater reliability of digital image analysis for skin color
      measurement.
AB  - BACKGROUND: We determined the intra- and inter-rater reliability of data from
      digital image color analysis between an expert and novice analyst. METHODS:
      Following training, the expert and novice independently analyzed 210 randomly
      ordered images. Both analysts used Adobe((r)) Photoshop lasso or color sampler
      tools based on the type of image file. After color correction with
      Pictocolor((r)) in camera software, they recorded L*a*b* (L*=light/dark;
      a*=red/green; b*=yellow/blue) color values for all skin sites. We computed intra
      rater and inter-rater agreement within anatomical region, color value (L*, a*,
      b*), and technique (lasso, color sampler) using a series of one-way intra-class
      correlation coefficients (ICCs). RESULTS: Results of ICCs for intra-rater
      agreement showed high levels of internal consistency reliability within each
      rater for the lasso technique (ICC >= 0.99) and somewhat lower, yet acceptable,
      level of agreement for the color sampler technique (ICC = 0.91 for expert, ICC =
      0.81 for novice). Skin L*, skin b*, and labia L* values reached the highest level
      of agreement (ICC >= 0.92) and skin a*, labia b*, and vaginal wall b* were the
      lowest (ICC >= 0.64). CONCLUSION: Data from novice analysts can achieve high
      levels of agreement with data from expert analysts with training and the use of a
      detailed, standard protocol.

PMID- 23551209
TI  - Glycoproteins in the buccal epithelium of a carp, Cirrhinus mrigala (Pisces,
      Cyprinidae): a histochemical profile.
AB  - Glycoproteins (GPs) were visualized histochemically in the secretory cells - the
      mucous goblet cells (the type A and the type B), the rodlet cells and the
      epithelial cells in different regions of the buccal cavity of Cirrhinus mrigala.
      The type A mucous goblet cells, the type B mucous goblet cells, the rodlet cells
      and the epithelial cells elaborate GPs with oxidizable vicinal diols and GPs with
      sialic acid residue without O-acyl substitution. The type A mucous goblet cells,
      in addition, contain moderate amounts of GPs with O-sulphate esters. The type B
      mucous goblet cells, in contrast, contain high concentrations of GPs with O
      sulphate esters. The rodlet cells secrete small amounts of GPs with oxidizable
      vicinal diols. The analysis of the results elucidates interesting differences in
      the composition and concentration of GPs in the mucus elaborated by the secretory
      cells indicating the potential importance of the glycoproteins in the buccal
      cavity. These GPs could be considered to represent a mechanism for modulation of
      the composition of the protective mucus layer correlated to specific functions. 

PMID- 23551211
TI  - Serendipitous assemblies of two large phosphonate cages: a Co15 distorted
      molecular cube and a Co12 butterfly type core structure.
AB  - This report describes the synthesis, characterization, and magnetic properties of
      two novel phosphonate-based Co(II) cages. Structural investigation reveals some
      interesting geometrical features in the molecular core that may provide new
      models in single molecular magnetic materials.

PMID- 23551210
TI  - A case-control study of bronchiolitis obliterans syndrome following allogeneic
      hematopoietic stem cell transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) is a significant complication after
      allogeneic hematopoietic stem cell transplantation (HSCT). However, the
      pathogenesis and risks for the development of BOS have remained unclear.
      Therefore, a case-control study was conducted to investigate the risk factors for
      the development of BOS, which included the largest number of BOS cases; 196
      patients with BOS were identified and compared with 1960 control recipients. The
      following were identified as significantly higher risk factors for the
      development of BOS: female recipients (OR 1.47, P = 0.019), ABO-mismatch HSCT
      (minor mismatch, OR 1.67, P = 0.015; major mismatch, OR 1.73, P = 0.012;
      bidirectional mismatch, OR 1.96, P = 0.018), busulfan+cyclophosphamide-based
      myeloablative conditioning (OR 1.74, P = 0.016), and acute graft-versus-host
      disease (GVHD) involving the skin (OR 1.55, P = 0.011). On the other hand, the
      risk for the development of BOS was significantly lower in patients receiving
      cord blood transplantation (OR 0.26, P = 0.0011). With respect to other target
      organs of chronic GVHD, ocular involvement was significantly associated with BOS
      (OR 2.53, P < 0.001). Prospective studies are required to elucidate the risk
      factors for the development of BOS, and future investigations should focus on
      finding a prophylactic approach against BOS based on these findings.

PMID- 23551212
TI  - Alliaceous migraines.
AB  - OBJECTIVE: To report a migraineur with osmophobia and trigger to garlic and onion
      aroma. BACKGROUND: While odors serve as a trigger in 70% of migraineurs,
      alliaceous aromas have been described only rarely. Furthermore, nor has more than
      one type of alliaceous odor acted as a trigger in the same individual. Neither
      has migraine with aura been described as precipitated by such aromas. A patient
      experiencing migraines with aura, triggered almost exclusively by alliaceous
      aromas, is described. METHODS:  CASE STUDY: 32-year-old woman; 5 years previously
      felt nasal pruritis upon eating a red onion dip. Shortly thereafter, the mere
      aroma of raw onions caused a sensation of her throat closing along with an
      associated panic attack. Over the intervening years, upon exposure to onions and
      garlic aroma she experienced a fortification spectra and visual entopia, followed
      by a bipareital, crushing level 10/10 headache, burning eyes and nose,
      lacrimation, perioral paresthesias, generalized pruritis, nausea, fatigue, sore
      throat, dysarthria, confusion, dyspnea, palpitations, presyncopal sensations,
      hand spasms, tongue soreness, neck pain, phonophobia, and photophobia. These
      would persist for 1 hour after leaving the aroma. She was unresponsive to
      medication and would wear a surgical mask when out. The patient also experienced
      chemosensory complaints: dysosmias every few months; phantosmias of food or
      cleaning products every month for a minute of level 5/10 intensity; pallinosmia
      of onion or garlic odor for 30 minutes after exposure; and metallic pallinugeusia
      after eating with metal utensils. RESULTS: Neurological exam normal except for
      bilateral positive Hoffman reflexes. CHEMOSENSORY TESTING: Quick Smell
      Identification Test 3/3 and Brief Smell Identification Test 12/12 were normal.
      Magnetic resonance imaging and computed tomography with and without contrast
      normal. Allergy skin test was positive for garlic and onion. Nose plug and
      counter stimulation with peppermint prevented the onset of headaches and
      associated symptoms. CONCLUSION: This is the first report of migraines with aura
      triggered by more than one alliaceous compound in the same individual. Possible
      mechanisms include odor induced, emotional change, vasomotor instability,
      trigeminal-induced neurogenic inflammation, and allergic response. In alliaceous
      and odor-induced migraines, a trial of counter stimulation and nose plugs is
      warranted.

PMID- 23551213
TI  - Blood pressure recordings during hemodialysis access interventions: implications
      for acute management.
AB  - A retrospective study evaluating the pattern of blood pressure and its related
      complications before, during, and after percutaneous hemodialysis interventions
      was performed in patients presenting with asymptomatic hypertension. Hemodialysis
      patients undergoing percutaneous interventions including tunneled hemodialysis
      catheter insertion, percutaneous balloon angioplasty and thrombectomy procedure,
      and stage II hypertension (systolic blood pressure >=160 mmHg) were included in
      this analysis. Blood pressure medications were not used while midazolam and
      fentanyl were routinely administered. Patients were followed for up to 4 weeks to
      monitor any complications. The mean blood pressure before, during, and after the
      procedures were 185 +/- 18/96 +/- 14, 172 +/- 22/92 +/- 15, and 153 +/- 25/87 +/-
      14, respectively. There was a statistically significant difference between the
      blood pressure readings before and after the procedure (before = 185 +/- 18/96 +/
      14, after = 153 +/- 25/87 +/- 14; p = 0.001). None of the patients had a stroke,
      myocardial infarction, or acute pulmonary edema before, during, or after the
      procedure or during the 4-week follow-up period. A significant reduction in blood
      pressure was observed after the procedure without the administration of any
      antihypertensive medication. These results suggest that the reduction in blood
      pressure observed after percutaneous dialysis access interventions (particularly
      in the presence of midazolam and fentanyl) may make it unnecessary to treat
      asymptomatic hypertension prior to these procedures.

PMID- 23551214
TI  - Combination of intense pulsed light and fractional CO(2) laser treatments for
      patients with acne with inflammatory and scarring lesions.
AB  - BACKGROUND: Various laser and light sources are been used increasingly in
      cosmetic dermatology. AIM: To evaluate the efficacy and safety of combination
      intense pulsed light (IPL) and fractional CO2 laser in treating patients with
      acne with both inflammatory and scarring lesions. METHODS: In total, 37 Chinese
      patients with acne with facial inflammatory and scar lesions were treated.
      Successive sessions of 4-6 IPL treatments followed by 2 sessions of fractional
      CO2 laser treatments were applied. Effectiveness was determined by the
      dermatologist's evaluation, patient self-assessment, and devices that measure
      skin colour, sebum secretion and skin hydration. RESULTS: IPL treatments
      significantly reduced the inflammatory lesion score and the atrophic scar score
      compared with baseline. Subsequent fractional CO2 laser treatments further
      decreased the atrophic scar score. Both scores remained low when patients were
      followed up at 6 months. Around 90% of the patients experienced significant or
      moderate overall improvement, and almost 80% patients rated their results as
      'excellent' or 'good'. The melanin index (MI), erythema index (EI) and skin sebum
      level all significantly decreased after IPL treatments, and the EI and sebum
      level were still low when assessed at the 3-month follow-up, although the MI had
      increased again. The adverse effects (AEs) of both treatments were transient and
      bearable. CONCLUSIONS: IPL in combination with fractional CO2 laser was effective
      in treating patients with acne with both inflammatory lesions and atrophic scars,
      and the AEs were acceptable.

PMID- 23551215
TI  - Simulation as a learning strategy: supporting undergraduate nursing students with
      disabilities.
AB  - AIMS AND OBJECTIVES: To promote simulation as a learning strategy to support
      undergraduate nursing students with disabilities. BACKGROUND: Supporting
      undergraduate nursing students with disabilities has gained further momentum
      because of amendments to the Disability Discrimination Act in 2009. Providers of
      higher education must now ensure proactive steps to prevent discrimination
      against students with a disability are implemented to assist in course
      progression. Simulation allows for the impact of a student's disability to be
      assessed and informs the determination of reasonable adjustments to be
      implemented. Further suitable adjustments can then be determined in a safe
      environment and evaluated prior to scheduled placement. Auditing in this manner,
      offers a risk management strategy for all while maintaining the academic
      integrity of the program. DESIGN: Discursive. METHODS: Low, medium and high
      fidelity simulation activities critically analysed and their application to
      support undergraduate nursing students with disabilities assessed. RESULTS: With
      advancing technology and new pedagogical approaches simulation as a learning
      strategy can play a significant role. In this role, simulation supports
      undergraduate nursing students with disabilities to meet course requirements,
      while offering higher education providers an important risk management strategy.
      CONCLUSION: The discussion recommends simulation is used to inform the
      determination of reasonable adjustments for undergraduate nursing students with
      disabilities as an effective, contemporary curriculum practice. Adoption of
      simulation, in this way, will meet three imperatives: comply with current
      legislative requirements, embrace advances in learning technologies and embed one
      of the six principles of inclusive curriculum. Achieving these imperatives is
      likely to increase accessibility for all students and offer students with a
      disability a supportive learning experience. RELEVANCE TO CLINICAL PRACTICE:
      Provides capacity to systematically assess, monitor, evaluate and support
      students with a disability. The students' reasonable adjustments can be
      determined prior to attending clinical practice to minimise risks and ensure the
      safety of all.

PMID- 23551216
TI  - Multicomponent assembly of diverse pyrazin-2(1H)-one chemotypes.
AB  - An expedient and concise Ugi-based approach for the rapid assembly of pyrazin
      2(1H)-one-based frameworks has been developed. This convergent approach
      encompasses skeletal, functional and stereochemical diversity, exhibiting an
      unusually high bond-forming efficiency as well as high structure and step
      economies. The method involves the use of readily available commercial reagents
      and is an example of the reconciliation of structural complexity with operational
      simplicity in a time- and cost-effective manner.

PMID- 23551218
TI  - The life of people born preterm - what do you want to know?

PMID- 23551219
TI  - Abstracts of the 47th Annual Scientific Meeting of the European Society for
      Clinical Investigation. Albufeira, Portugal. April 17-20, 2013.

PMID- 23551217
TI  - Effect of D-cycloserine in conjunction with fear extinction training on
      extracellular signal-regulated kinase activation in the medial prefrontal cortex
      and amygdala in rat.
AB  - D-cycloserine (DCS) is currently under clinical trials for a number of
      neuropsychiatric conditions and has been found to augment fear extinction in
      rodents and exposure therapy in humans. However, the molecular mechanism of DCS
      action in these multiple modalities remains unclear. Here, we describe the effect
      of DCS administration, alone or in conjunction with extinction training, on
      neuronal activity (c-fos) and neuronal plasticity [phospho-extracellular signal
      regulated kinase (pERK)] markers using immunohistochemistry. We found that
      intraperitoneal administration of DCS in untrained young rats (24-28 days old)
      increased c-fos- and pERK-stained neurons in both the prelimbic and infralimbic
      division of the medial prefrontal cortex (mPFC) and reduced pERK levels in the
      lateral nucleus of the central amygdala. Moreover, DCS administration
      significantly increased GluA1, GluN1, GluN2A, and GluN2B expression in the mPFC.
      In a separate set of animals, we found that DCS facilitated fear extinction and
      increased pERK levels in the infralimbic prefrontal cortex, prelimbic prefrontal
      cortex intercalated cells and lateral nucleus of the central amygdala, compared
      with saline control. In the synaptoneurosomal preparation, we found that
      extinction training increased iGluR protein expression in the mPFC, compared with
      context animals. No significant difference in protein expression was observed
      between extinction-saline and extinction-DCS groups in the mPFC. In contrast, in
      the amygdala DCS, the conjunction with extinction training led to an increase in
      iGluR subunit expression, compared with the extinction-saline group. Our data
      suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due
      to its ability to affect neuronal activity and signaling in the mPFC and amygdala
      subnuclei.

PMID- 23551220
TI  - Successful treatment with oral alitretinoin in women of childbearing potential
      with Darier's disease.

PMID- 23551221
TI  - The complete mitochondrial genome of variegated lizardfish Synodus variegatus
      (Aulopiformes, Synodontidae).
AB  - In this study, the complete mitogenome sequence of variegated lizardfish Synodus
      variegatus (Lacepede, 1803) (Perciformes, Synodontidae) has been amplified and
      sequenced employing the long polymerase chain reaction method. The mitogenome,
      consisting of 16,448 base pairs (bp), had the typical vertebrate mitochondrial
      gene arrangement, including 13 protein-coding, 22 transfer RNAs, 2 ribosomal RNAs
      genes and a noncoding control region (CR). The CR of 830 bp length is rather
      compact and located between tRNA(Pro) and tRNA(Phe). The overall base composition
      of Myxocyprinus asiaticus is 26.36% for A, 27.69% for C, 26.99% for T and 18.95%
      for G, with a slight AT bias of 53.36%. The complete mitogenome may provide
      important DNA molecular data for further phylogenetic analyses for higher taxa of
      teleost fishes, especially for the fishes of order Aulopiformes.

PMID- 23551222
TI  - Relating rheological measurements to primary and secondary skin feeling when
      mineral-based and Fischer-Tropsch wax-based cosmetic emulsions and jellies are
      applied to the skin.
AB  - Rheology measurements were correlated to skin sensations occurring when cream and
      petroleum jelly cosmetic products containing different amounts of synthetic
      Fischer-Tropsch wax were applied to the skin. A panel of 15 people with a
      background in cosmetic product development were asked to rate skin feelings when
      a range of petroleum jelly and cream samples are applied to the skin. Primary
      skin feel, or the spreadability of a cosmetic product, was correlated to the
      product's flow onset and maximum viscosity as measured by a Anton Paar rheometer,
      whereas secondary skin feel or the sensation occurring at the end of application
      when the product was completely rubbed into the skin was correlated to the
      product's viscosity measured at high shear rates. The cream samples prepared with
      a petroleum jelly containing 10% and 20% Fischer-Tropsch wax fell within the
      boundary of good primary skin feeling of cream products. Predominantly, synthetic
      petroleum jellies were given the best assessments in terms of primary skin
      feeling and were used with mineral-based petroleum jellies to determine the
      boundary of good primary skin feeling for petroleum jelly products. The further
      away a product falls from this rheological boundary the poorer the skin feeling
      assessment appears to be by the panel. Products containing Fischer-Tropsch waxes
      were given the best assessment by the panel for secondary skin feeling. Comments
      from the panel include that these products feel silky and light on the skin. The
      higher the Fischer-Tropsch wax content, the lower viscosity was at high shear
      rate (Upsilon = 500 s(-1) ) and the higher the assessment by the panel.
      Rheological measurements can be used to objectively determine skin sensation when
      products are applied to the skin; this may shorten research and development
      times. A rheology boundary of certain product viscosity and shear stress applied
      is associated with good primary skin feeling for lotions, creams and petroleum
      jellies. Lower product viscosity at high shear rate seems to be associated with
      better secondary skin feeling. Products with higher Fischer-Tropsch wax content
      appear to be rated higher in terms of secondary skin feeling. 

PMID- 23551223
TI  - Effect of sequestering intrinsic iron on the electron paramagnetic resonance
      signals in powdered soy proteins.
AB  - This investigation examined iron in powdered soy protein products using electron
      paramagnetic resonance (EPR) spectroscopy, and the effect that selectively
      binding free iron in isolated soy protein (ISP) had on the occurrence of
      metastable radicals in powdered soy proteins. EPR analyses of soybean defatted
      flour, commercial ISP and laboratory ISP samples revealed a peak at g = 4.3
      characteristic of high-spin ferric iron in a rhombic-coordinated environment.
      Commercial ISP samples examined contained higher levels of the rhombic ferric
      iron than laboratory-prepared ISP samples. During the first 6 wk of storage the
      primary singlet EPR signal at g = 2.0049 in the commercial ISP samples
      approximately doubled, and the laboratory prepared samples increased by about 9
      fold. The EPR signal was initially about 4-times higher in the freshly prepared
      commercial samples compared to the corresponding laboratory ISP. Laboratory ISP
      samples prepared with added deferoxamine to sequester endogenous iron exhibited a
      large increase in the high-spin ferric iron EPR signal at g = 4.3. ISP treated
      with deferoxamine also exhibited a multiple-line EPR signal at about g = 2.007,
      instead of the typical singlet signal at g = 2.0049. The power at which the
      signal amplitude was half-saturated also changed from about 1 mW in the control
      ISP to about 20 mW in the deferoxamine treated ISP. The multiple-line EPR
      spectrum from the ISP treated with deferoxamine increased during storage over a 6
      wk period by about 6-fold. The observed changes in EPR line-shape, g-value, and
      power saturation with the deferoxamine treatment indicate that the primary free
      radical signal in powdered ISP samples may be from stabilized tyrosine radicals
      with spin densities distributed over the aromatic ring.

PMID- 23551224
TI  - Influence of hydrogen bonding effects on methanol and water diffusivities in acid
      base polymer blend membranes of sulfonated poly(ether ether ketone) and base
      tethered polysulfone.
AB  - Atomistic molecular dynamics simulations were used to study the water and
      methanol diffusivities in acid-base polymer blend membranes consisting of
      sulfonated poly(ether ether ketone) (SPEEK) and polysulfone tethered with
      different bases (2-amino-benzimidazole, 5-amino-benzotriazole, and 1H
      perimidine). Consistent with experimental trends, methanol and water
      diffusivities in all the SPEEK-based systems were found to be lower than those in
      Nafion. When the base group attached to the polysulfone was varied, the methanol
      diffusivities were found to exhibit the same trends as observed in the
      experimentally measured crossover current densities. Such trends were however
      observed only when we explicitly accounted for hydrogen bonding interactions
      between the hydrogen attached to the nitrogen of the base and the oxygen of the
      sulfonate of SPEEK. Furthermore, in almost all cases, methanol diffusivities were
      found to be highly correlated with the pore sizes of the membranes, which, in the
      case of blends, were found to be influenced by the strength of parasitic hydrogen
      bonding interactions between the sulfone oxygen of polysulfone and H(N-base). The
      influence of pore sizes on the methanol diffusivity behavior was rationalized by
      using both the coordination behavior and the residence time distributions of
      methanol in various regions of pores. Together, our results unravel the
      physicochemical origins of methanol diffusivities in acid-base blend membranes
      and highlight the crucial role played by the hydrogen bonding interactions in
      influencing methanol transport in acid-base polymer blend membranes.

PMID- 23551225
TI  - Response.

PMID- 23551226
TI  - The domain of unknown function DUF1521 exhibits metal ion-inducible autocleavage
      activity - a novel example from a putative effector protein of Vibrio
      coralliilyticus ATCC BAA-450.
AB  - Vibrio coralliilyticus ATCC BAA-450 is a pathogen causing coral bleaching at
      elevated seawater temperatures. Based on the available genome sequence, the
      strain has a type III secretion system. Within the corresponding gene cluster,
      VIC_001052 is encoded, which contains a conserved domain of unknown function
      DUF1521. In this study, we show that the purified domain exhibits autocleavage
      activity in the presence of several divalent metal ions, for example, calcium and
      manganese but not with magnesium or zinc. Autocleavage is not affected by
      temperatures between 0 and 30  degrees C, indicating that seawater temperature is
      not a critical factor for this activity. The DUF1521 domain and the cleavage site
      are conserved in several proteins from proteobacteria, suggesting a similar
      cleavage activity for these proteins.

PMID- 23551227
TI  - The importance of family functioning, mental health and social and emotional well
      being on child oral health.
AB  - OBJECTIVE: To examine the strength of associations between child oral health and
      aspects of the home environment (child behaviour, parental psychological distress
      and family functioning) in a large sample of 1- to 12-year-old Australian
      children. METHODS: The current study used data from the 2006 Victorian Child
      Health and Wellbeing Study. Data were obtained on 4590 primary carers. Measures
      of the family environment included the level of family functioning, parental
      psychological distress, child's emotion and behavioural problems and the family
      structure. RESULTS: The odds of children having good oral health status were
      lower with increasing parental psychological distress and poor family functioning
      across all age groups, and lower with increasing child mental health or conduct
      problems among children aged 4 years or older. Socioeconomic factors were also
      related to child oral health status, but this was significant only among children
      aged 4-7 years, with the odds of children having good oral health status 68%
      higher in households with a yearly income >=AUD$ 60 000 compared with households
      with income <$20 000 (P < 0.05). CONCLUSION: In order to address inequities in
      the experience of poor oral health, solutions that encompass social, economic and
      psychosocial dimensions will be required. Integrating intervention strategies
      that promote oral, healthy family functioning and the mental health of parents
      and children into existing systems reaching vulnerable community members may
      improve child oral health outcomes and reduce the unequal distribution of oral
      disease across the social gradient.

PMID- 23551228
TI  - Lead theft--a study of the "uniqueness" of lead from church roofs.
AB  - In the United Kingdom, theft of lead is common, particularly from churches and
      other public buildings with lead roofs. To assess the potential to distinguish
      lead from different sources, 41 samples of lead from 24 church roofs in
      Northamptonshire, U.K, have been analyzed for relative abundance of trace
      elements and isotopes of lead using X-ray fluorescence (XRF) and inductively
      coupled plasma mass spectrometry, respectively. XRF revealed the overall presence
      of 12 trace elements with the four most abundant, calcium, phosphorus, silicon,
      and sulfur, showing a large weight percentage standard error of the mean of all
      samples suggesting variation in the weight percentage of these elements between
      different church roofs. Multiple samples from the same roofs, but different lead
      sheets, showed much lower weight percentage standard errors of the mean
      suggesting similar trace element concentrations. Lead isotope ratios were similar
      for all samples. Factors likely to affect the occurrence of these trace elements
      are discussed. 

PMID- 23551230
TI  - Covered self-expandable metal stent deployment promises safe neoadjuvant
      chemoradiation therapy in patients with borderline resectable pancreatic head
      cancer.
AB  - BACKGROUND: Patients with borderline resectable pancreatic head cancer (BRPHC)
      have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic
      stents. The aim of the present study was to evaluate the efficacy and
      complications of covered self-expanding metallic stents (CSEMS) during the NACRT
      and surgical period. PATIENTS AND METHODS: We reviewed the outcomes of patients
      with BRPHC, then divided them chronologically into three groups as follows. Group
      A: upfront surgery with plastic stent (PS) deployment; group B: PS deployment
      plus neoadjuvant chemotherapy (NAC) and/or NACRT; group C: CSEMS deployment plus
      NAC/NACRT. Patients were categorized as borderline resectable based on National
      Comprehensive Cancer Network Guidelines, 2010. Days to reintervention (DR),
      reintervention rate, and the rate of R0 and complications were studied. Safe
      margin-negative resection (R0) surgery was defined as R0 surgery without
      reintervention during the NACRT period and no postoperative complications.
      RESULTS: DR were as follows. Groups A, B and C were 32, 55 and 97 days,
      respectively (P < 0.05). R0 surgery obtained in groups A, B and C was 53% (9/17),
      100% (17/17) and 93% (14/15), respectively. CSEMS did not interfere with surgery.
      Safe R0 surgery obtained in groups B and C was 11% (2/19) and 67% (10/15),
      respectively (P < 0.05). Multivariate analysis showed that the odds ratio for
      safe R0 surgery was 16.210 (95% CI 2.457-106.962, P = 0.003) for CSEMS placement.
      CONCLUSION: CSEMS should be considered to relieve symptomatic biliary obstruction
      in patients with BRPHC receiving NACRT in view of the high attainability rate of
      safe R0 surgery compared to that with PS deployment.

PMID- 23551229
TI  - The rice narrow leaf2 and narrow leaf3 loci encode WUSCHEL-related homeobox 3A
      (OsWOX3A) and function in leaf, spikelet, tiller and lateral root development.
AB  - . In order to understand the molecular genetic mechanisms of rice (Oryza sativa)
      organ development, we studied the narrow leaf2 narrow leaf3 (nal2 nal3; hereafter
      nal2/3) double mutant, which produces narrow-curly leaves, more tillers, fewer
      lateral roots, opened spikelets and narrow-thin grains. . We found that narrow
      curly leaves resulted mainly from reduced lateral-axis outgrowth with fewer
      longitudinal veins and more, larger bulliform cells. Opened spikelets, possibly
      caused by marginal deformity in the lemma, gave rise to narrow-thin grains. . Map
      based cloning revealed that NAL2 and NAL3 are paralogs that encode an identical
      OsWOX3A (OsNS) transcriptional activator, homologous to NARROW SHEATH1 (NS1) and
      NS2 in maize and PRESSED FLOWER in Arabidopsis. . OsWOX3A is expressed in the
      vascular tissues of various organs, where nal2/3 mutant phenotypes were
      displayed. Expression levels of several leaf development-associated genes were
      altered in nal2/3, and auxin transport-related genes were significantly changed,
      leading to pin mutant-like phenotypes such as more tillers and fewer lateral
      roots. OsWOX3A is involved in organ development in rice, lateral-axis outgrowth
      and vascular patterning in leaves, lemma and palea morphogenesis in spikelets,
      and development of tillers and lateral roots.

PMID- 23551231
TI  - Maximising the net social benefit of the construction of post-disaster
      alternative housing projects.
AB  - The widespread destruction that follows large-scale natural disasters, such as
      Hurricane Katrina in August 2005, challenges the efficacy of traditional
      temporary housing methods in providing adequate solutions to housing needs.
      Recognising these housing challenges, the Congress of the United States
      allocated, in 2006, USD 400 million to the Department of Homeland Security to
      support Alternative Housing Pilot Programs, which are intended to explore the
      possibilities of providing permanent and affordable housing to displaced families
      instead of traditional temporary housing. This paper presents a new methodology
      and optimisation model to identify the optimal configurations of post-shelter
      housing arrangements to maximise the overall net socioeconomic benefit. The model
      is capable of quantifying and optimising the impacts of substituting temporary
      housing with alternative housing on the social and economic welfare of displaced
      families as well as the required additional costs of doing so. An application
      example is presented to illustrate the use of the model and its capabilities.

PMID- 23551232
TI  - Machine perfusion versus static cold storage in expanded criteria donor kidney
      transplantation: 3-year follow-up data.

PMID- 23551233
TI  - Manganese(II), iron(II), and mixed-metal metal-organic frameworks based on chains
      with mixed carboxylate and azide bridges: magnetic coupling and slow relaxation.
AB  - Mn(II) and Fe(II) compounds derived from azide and the zwitterionic 1
      carboxylatomethylpyridinium-4-carboxylate ligand are isomorphous three
      dimensional metal-organic frameworks (MOFs) with the sra net, in which the metal
      ions are connected into anionic chains by mixed (MU-1,1-azide)bis(MU-carboxylate)
      triple bridges and the chains are cross-linked by the cationic backbones of the
      zwitterionic ligands. The Mn(II) MOFs display typical one-dimensional
      antiferromagnetic behavior. In contrast, with one more d electron per metal
      center, the Fe(II) counterpart shows intrachain ferromagnetic interactions and
      slow relaxation of magnetization attributable to the single-chain components. The
      activation energies for magnetization reversal in the infinite- and finite-chain
      regimes are Deltatau1 = 154 K and Deltatau2 = 124 K, respectively. Taking
      advantage of the isomorphism between the Mn(II) and Fe(II) MOFs, we have prepared
      a series of mixed-metal Mn(II)(1-x)Fe(II)(x) MOFs with x = 0.41, 0.63, and 0.76,
      which intrinsically feature random isotropic/anisotropic sites and competing
      antiferromagnetic-ferromagnetic interactions. The materials show a gradual
      antiferromagnetic-to-ferromagnetic evolution in overall behaviors as the Fe(II)
      content increases, and the Fe-rich materials show complex relaxation processes
      that may arise for mixed SCM and spin-glass mechanisms. A general trend is that
      the activation energy and the blocking temperature increase with the Fe(II)
      content, emphasizing the importance of anisotropy for slow relaxation of
      magnetization.

PMID- 23551235
TI  - Prevalence, correlation and clinical outcome of intra-procedural stent thrombosis
      in patients undergoing primary percutaneous coronary intervention for acute
      coronary syndrome.
AB  - OBJECTIVES: To assess the occurrence, correlation, and clinical outcome of
      intraprocedural stent thrombosis (IPST) in patients undergoing primary
      percutaneous coronary intervention (PCI) in the setting of acute coronary
      syndromes (ACSs). BACKGROUND: Stent thrombosis (ST), a rare complication of PCI,
      is more common in the setting of ACS. It is not known whether IPST carries the
      same prognosis as postprocedural ST. METHODS: This retrospective study comprised
      a review of 1,901 consecutive ACS patients who received primary PCI in our center
      from January 2006 to January 2011. IPST was defined as new, reappearing or
      increased thrombus within the deployed stent before the index PCI procedure was
      completed. All angiograms were independently reviewed frame by frame for the
      incidence of IPST. Patients with and without IPST were compared with respect to
      clinical characteristics, angiographic parameters, and major adverse cardiac
      events (MACEs) at 30 days and 1-year follow-up. RESULTS: Overall, there were 23
      cases of IPST detected, thus, the prevalence of IPST was 1.2%. There were no
      significant differences in baseline clinical characteristics between the 2
      groups. Patients with compared to those without IPST had significantly more
      bifurcation lesions involved, and more thrombus burden at baseline. IPST group
      compared to no IPST group had more MACEs on 30 days (26.1% vs. 8.7%, P = 0.01)
      and 1-year follow-up (30.4% vs. 14.4%, P = 0.02). CONCLUSIONS: IPST was a rare
      complication of PCI in the setting of ACS. It correlated with lesion morphology,
      presence of thrombus at baseline and was more likely to cause MACEs in 30 days
      and 1-year follow-up.

PMID- 23551236
TI  - Painful subungual tumours.

PMID- 23551234
TI  - Heat-shock proteins as dendritic cell-targeting vaccines--getting warmer.
AB  - Heat-shock proteins (hsp) provide a natural link between innate and adaptive
      immune responses by combining the ideal properties of antigen carriage
      (chaperoning), targeting and activation of antigen-presenting cells (APC),
      including dendritic cells (DC). Targeting is achieved through binding of hsp to
      distinct cell surface receptors and is followed by antigen internalization,
      processing and presentation. An improved understanding of the interaction of hsp
      with DC has driven the development of numerous hsp-containing vaccines, designed
      to deliver antigens directly to DC. Studies in mice have shown that for cancers,
      such vaccines generate impressive immune responses and protection from tumour
      challenge. However, translation to human use, as for many experimental
      immunotherapies, has been slow partly because of the need to perform trials in
      patients with advanced cancers, where demonstration of efficacy is challenging.
      Recently, the properties of hsp have been used for development of prophylactic
      vaccines against infectious diseases including tuberculosis and meningitis. These
      hsp-based vaccines, in the form of pathogen-derived hsp-antigen complexes, or
      recombinant hsp combined with selected antigens in vitro, offer an innovative
      approach against challenging diseases where broad antigen coverage is critical.

PMID- 23551237
TI  - Development process and psychometric testing of foot health assessment
      instrument.
AB  - AIMS AND OBJECTIVES: To describe the development process of the foot health
      assessment instrument for the assessment of foot health in older people and to
      evaluate the psychometric properties of the foot health assessment instrument.
      BACKGROUND: In clinical nursing, assessment of foot health and recognition of
      foot problems in older people is fundamental for maintain older persons'
      independent functional ability. However, valid and reliable nurse-administered
      foot health assessment instruments are lacking. DESIGN: A cross-sectional
      methodological design. METHODS: The foot health assessment instrument was
      developed in 2008-2011 based on a literature review and expertise in podiatry and
      nursing. Content validity was evaluated in four expert panels. Inter-rater
      reliability between nurses' and researcher (MS) assessments was evaluated in the
      pilot test and in the empirical testing of the instrument with a sample of
      visiting home nurses. Inter-rater reliability was calculated with Cohen's kappa,
      internal consistency reliability was examined with Cronbach's alpha coefficients
      and item analysis, and construct validity was evaluated by principal component
      analysis with Varimax rotation and confirmatory factor analysis. RESULTS: Content
      validity was guaranteed by the expert analyses. Inter-rater reliability improved
      after pilot test. The Cronbach's alpha coefficient for the total foot health
      assessment instrument was satisfactory. Item-to-total correlations varied between
      but most of them were acceptable. Principal component analysis and confirmatory
      factor analysis supported the four component structure of the foot health
      assessment instrument. CONCLUSIONS: The 23-item foot health assessment instrument
      showed preliminary acceptable psychometric properties. However, further
      modifications and testing are needed to strengthen the psychometric properties of
      the foot health assessment instrument. RELEVANCE TO CLINICAL PRACTICE: The
      existence of a foot health assessment instrument and its application would
      considerably improve the assessment of foot health in daily nursing practice. The
      foot health assessment instrument developed in this study is short and easy to
      administer.

PMID- 23551238
TI  - The "strong" RNA world hypothesis: fifty years old.
AB  - This year marks the 50(th) anniversary of a proposal by Alex Rich that RNA, as a
      single biopolymer acting in two capacities, might have supported both genetics
      and catalysis at the origin of life. We review here both published and previously
      unreported experimental data that provide new perspectives on this old proposal.
      The new data include evidence that, in the presence of borate, small amounts of
      carbohydrates can fix large amounts of formaldehyde that are expected in an
      environment rich in carbon dioxide. Further, we consider other species, including
      arsenate, arsenite, phosphite, and germanate, that might replace phosphate as
      linkers in genetic biopolymers. While linkages involving these oxyanions are
      judged to be too unstable to support genetics on Earth, we consider the
      possibility that they might do so in colder semi-aqueous environments more exotic
      than those found on Earth, where cosolvents such as ammonia might prevent
      freezing at temperatures well below 273 K. These include the ammonia-water
      environments that are possibly present at low temperatures beneath the surface of
      Titan, Saturn's largest moon.

PMID- 23551239
TI  - Type IV kerogens as analogues for organic macromolecular materials in aqueously
      altered carbonaceous chondrites.
AB  - Understanding the processes involved in the evolution of organic matter in the
      early Solar System requires extensive experimental work. The scientifically
      valuable carbonaceous chondrites are principal targets for organic analyses, but
      these meteorites are rare. Meteoritic analog materials available in larger
      quantities, on which experiments can be performed, would be highly beneficial.
      The bulk of the organic inventory of carbonaceous chondrites is made up of
      solvent-insoluble macromolecular material. This high-molecular-weight entity
      provides a record of thermal and aqueous parent-body alteration of precursor
      organic structures present at the birth of the Solar System. To identify an
      effective analogue for this macromolecular material, we analyzed a series of
      terrestrial kerogens by pyrolysis-gas chromatography-mass spectrometry. Type I
      and II kerogens are unsuitable analogues owing to their highly aliphatic nature.
      Type III kerogens show some similarities to meteoritic macromolecular materials
      but display a substantial biological heritage. Type IV kerogens, in this study
      derived from Mesozoic paleosols and produced by the reworking and oxidation of
      organic matter, represent an effective analogue. Some isomeric differences exist
      between meteoritic macromolecular materials and type IV kerogens, and stepped
      pyrolysis indicates variations in thermal stability. In addition to being a
      suitable material for novel experimentation, type IV kerogens also have the
      potential to aid in the optimization of instruments for deployment on Mars.

PMID- 23551240
TI  - Thermochemical studies of epoxides and related compounds.
AB  - Gas-phase heats of formation for the four butene oxide isomers are reported. They
      were obtained by measuring the condensed-phase heat of reduction to the
      corresponding alcohol using reaction calorimetry. Heats of vaporization were
      determined and allow gas-phase heats of formation to be obtained. The
      experimental measurements are compared to calculations obtained using a variety
      of computational methods. Overall, the G3 and CBS-APNO methods agree quite well
      with the experimental data. The influence of alkyl substituents on epoxide
      stability is discussed. Comparisons to alkenes, cyclopropanes, aziridines,
      thiiranes, and phosphiranes are also made. Isodesmic-type reactions were used to
      determine strain energies of the epoxides and related compounds with various
      substituents.

PMID- 23551241
TI  - Phenobarbital-induced severe cutaneous adverse drug reactions are associated with
      CYP2C19*2 in Thai children.
AB  - BACKGROUND: Aromatic anticonvulsant-induced severe cutaneous adverse drug
      reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal
      necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS),
      are fatal immune-mediated adverse drug reactions. CYP2C19, a cytochrome P450
      isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA-B*1502
      has also been demonstrated to be associated with carbamazepine-induced SJS-TEN.
      METHODS: Forty case patients who were diagnosed with SCARs after initiation of
      phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) for 1-8 wk and forty
      control patients who received PB, PHT, or CBZ at least 2 months with no adverse
      drug reactions were enrolled in the study. The genotypes of CYP2C19*1, CYP2C19*2,
      and HLA-B*1502 were analyzed using allele-specific polymerase chain reaction
      technique. Clinical characteristics of SCARs patients who used different drugs
      were also analyzed. RESULTS: There was no significant difference in sex, onset of
      symptoms, laboratory results, treatment, and length of stay among patients with
      SCARs due to PB, PHT, or CBZ. The patients with CYP2C19*2 variant had a trend to
      have a likelihood to develop SCARs more than the patients with CYP2C19 wild type
      (OR = 2.5, 95% CI (0.96-67.3) p = 0.06). In subgroup analysis, the patients with
      CYP2C19*2 variant were at four times increased risk of SCARs from phenobarbital
      more than the patients with CYP2C19 wild type (OR = 4.5, 95% CI (1.17-17.37) p <
      0.03). There was no association between the HLA-B*1502 and aromatic
      anticonvulsant-induced severe cutaneous adverse reactions (SCARs). CONCLUSION:
      CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from
      phenobarbital.

PMID- 23551242
TI  - Haloperidol-induced striatal Nur77 expression in a non-human primate model of
      tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is a delayed and potentially irreversible motor
      complication arising in patients chronically exposed to antipsychotic drugs. As
      several modern (so-called atypical) antipsychotic drugs are common offenders,
      combined with the widening clinical indications for prescription as well as
      exposure of vulnerable individuals, TD will remain a significant drug-induced
      unwanted side effect. In addition, the pathophysiology of TD remains elusive and
      therapeutics are difficult. Based on rodent experiments, we have previously shown
      that the transcriptional factor Nur77 (also known as nerve growth factor
      inducible gene B or Nr4a1) is induced in the striatum following antipsychotic
      drug exposure as part of a long-term neuroadaptive process. To confirm this, we
      exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with
      haloperidol (median 18.5 months, N = 11) or clozapine (median 6 months, N = 6).
      Six untreated animals were used as controls. Five haloperidol-treated animals
      developed mild TD movements similar to those found in humans. No TD was observed
      in the clozapine group. Postmortem analysis of Nur77 expression measured by in
      situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA
      levels in the caudate-putamen were strongly upregulated in animals exposed to
      haloperidol but were spared following clozapine treatment. Interestingly, within
      the haloperidol-treated group, TD-free animals showed higher Nur77 expression in
      putamen subterritories compared with dyskinetic animals. This suggests that Nur77
      expression might be associated with a reduced risk of TD in this experimental
      model and could provide a novel target for drug intervention. 

PMID- 23551243
TI  - Effect of vitamin D supplementation and ultraviolet B exposure on serum 25
      hydroxyvitamin D concentrations in healthy volunteers: a randomized, crossover
      clinical trial.
AB  - BACKGROUND: Solar ultraviolet (UV) radiation during the summer and vitamin D
      supplementation are two major sources of vitamin D for humans at northern
      latitudes. However, little is known about the relative efficiency of these two
      vitamin D sources. OBJECTIVES: The main goal was to compare the efficiency of
      high-dose oral vitamin D3 supplementation (2000 IU per day for 30 days) with a
      simulated summer UV exposure [10 sunbed sessions to a total dose of 23.8 standard
      erythema doses (SED)] to improve vitamin D status. METHODS: Healthy volunteers
      were randomized into two groups: group 1 received vitamin D supplementation
      followed by 10 whole-body sunbed exposures; group 2 started with 10 sunbed
      exposures followed by vitamin D supplementation. RESULTS: The oral
      supplementation with vitamin D3 resulted in a mean (SEM) serum 25-hydroxyvitamin
      D [25(OH)D] increase of 25.3 (5.4) nmol L(-1) . A similar increase, 19.8 (5.4)
      nmol L(-1) , was observed after simulated summer UV exposure. At the end of the
      study, serum 25(OH)D concentrations were similar in both groups. CONCLUSIONS:
      Twice-weekly whole-body sunbed exposure to a dose of 4.8 SED is equal to 2000 IU
      daily of oral vitamin D supplementation for 30 days and enough to achieve and
      maintain serum 25(OH)D concentrations > 75 nmol L(-1) in ~55% of cases. Based on
      our calculations, this dose corresponds to a cumulative weekly whole-body
      exposure of 3.4 SED (~ 40 min around midday during the summer at the latitude of
      Oslo).

PMID- 23551244
TI  - Alzheimer's disease and granulocyte density diversity.
AB  - BACKGROUND: The current study investigates circulating eosinophils and
      neutrophils in Alzheimer's (AD) type dementia with respect to density (kg/L). The
      existence of beta-amyloid plaques in the brain is a feature of AD. Sporadic
      scientific reports indicate that the disease affects circulating neutrophils. In
      contrast, numerous publications investigate inflammatory reactions in AD brains.
      Locally, the plaques evoke a substantial inflammatory response involving
      activated microglia and astrocytes. METHODS: Subjects with probable AD (n = 39)
      were included and compared with elderly individuals (n = 22) lacking apparent
      memory problems. We sampled 10 mL venous blood in citrate. Granulocytes were
      separated according to density in linear PercollTM gradients. Subsequently, the
      gradients were divided into density subfractions (n = 16). In every fraction,
      determination of eosinophil and neutrophil counts was carried out. RESULTS: AD
      sufferers displayed less granulocytes in fractions nos. 13-15 containing light
      cells. For these fractions, the P-values proved to be (P < 0.001; not
      significant; P = 0.03) and (P = 0.01; P = 0.01; not significant), for eosinophils
      and neutrophils, respectively. CONCLUSIONS: The present work describes that less
      circulating light granulocytes are a feature of AD demented individuals. It is to
      hypothesize that it is a sign of impaired granulocyte turnover and cell damage.
      It is concluded that AD affects inflammatory cells in the periphery and that the
      behaviour of granulocytes in dementia is worthwhile further studies.

PMID- 23551245
TI  - Lung development in children: role of genetic and environmental factors.

PMID- 23551246
TI  - Seasonal variation in proximate composition and fatty acid profile of grey
      triggerfish (Balistes capriscus) captured along the coast of Portugal.
AB  - Proximate composition (ash, moisture, total protein, and fat contents) and fatty
      acid profile of Balistes capriscus (grey triggerfish) were assessed over a 6
      months period (April to September, 2011) in animals captured along the coast of
      Peniche (Portugal). High protein (18.9% to 21.4%) and low lipid (0.5% to 0.8%)
      contents were determined. The highest lipid level was found in June-captured
      animals. High proportions of n-3 polyunsaturated fatty acids (n-3 PUFA) were
      observed (53.87 +/- 2.00%) together with substantial quantities of oleic acid
      (27.58 +/- 1.09%) and palmitic acid (16.52 +/- 0.93%). Docosahexaenoic acid
      accounted for 77% of the total PUFA and was 7 times more abundant than
      eicosapentaenoic acid, and the n-3/n-6 ratio was 7.2. Gender did not influence
      lipid levels and the fatty acid profile, but seasonal variations were observed
      for PUFA and monounsaturated fatty acid contents. Overall, the nutritional
      properties of this underexploited species may be comparable to those of other
      lean fish species with higher economic value.

PMID- 23551247
TI  - Effect of calcium hydroxide and endodontic irrigants on fibre post bond strength
      to root canal dentine.
AB  - AIM: To analyse the effect of calcium hydroxide paste, endodontic irrigants and
      time of application on the bond strength of fibre posts to root canal dentine.
      METHODOLOGY: Seventy bovine incisors were divided into 7 groups according to
      removal of calcium hydroxide and distilled water (CHW) (immediate - I; 21 days -
      21 days; 6 months - 6 months) and endodontic irrigant (1% sodium hypochlorite -
      SH; 1% sodium hypochlorite + 17% EDTA - SHE). Fibre posts were cemented (RelyX
      U100), after which the roots were serially sectioned and submitted to a micro
      push-out test. Data were analysed using two-way anova followed by the Tukey's and
      the Dunnett's tests (alpha = 0.05). RESULTS: The CHW groups were not
      significantly different from the control group in 13 of the 18 associated factors
      (P > 0.05). There were significant reductions in bond strength in the cervical (P
      = 0.0216) and middle (P = 0.0017) thirds of the root at 6 months in groups
      irrigated with SH. Irrigation with SHE reduced the bond strength significantly in
      the middle (P = 0.0488) and apical (P = 0.0252) thirds of the roots in the
      immediate groups and in the middle third (P = 0.0287) in the 21-day group. Bond
      strength was greater in the cervical than in the apical thirds of all immediate
      and 21-day groups (P < 0.05). CONCLUSIONS: Bond strength of groups that received
      CH paste was similar to that found in the control group in 13 of the 18
      associated factors. EDTA and SH reduced bond strength in specimens in the
      immediate (middle and apical thirds) and 21-day (middle third) groups. There was
      a significant reduction in bond strength in the groups irrigated with SH and
      tested at 6 months (cervical and middle thirds). There was a predominance of
      adhesive failures between resin cement and dentine in all groups.

PMID- 23551249
TI  - Diabetes care in England and Wales: information from the 2010-2011 National
      Diabetes Audit.

PMID- 23551248
TI  - Studies on the mechanism of telavancin decreased susceptibility in a laboratory
      derived mutant.
AB  - Telavancin is a novel semisynthetic lipoglycopeptide derivative of vancomycin
      with a dual mode of action. This study sought to understand the mechanisms of
      decreased telavancin susceptibility in a laboratory-derived Staphlococcus aureus
      mutant Tlv(DS)MED1952. There were extensive changes in the transcriptome of
      Tlv(DS)MED1952 compared to the susceptible parent strain MED1951. Genes
      upregulated included cofactor biosynthesis genes, cell wall-related genes, fatty
      acid biosynthesis genes, and stress genes. Downregulated genes included lysine
      operon biosynthesis genes and lrgB, which are induced by telavancin in
      susceptible strains, agr and kdpDE genes, various cell surface protein genes,
      phenol-soluble modulin genes, several protease genes, and genes involved in
      anaerobic metabolism. The decreased susceptibility mutant had somewhat thicker
      cell walls and a decreased autolytic activity that may be related to decreased
      proteolytic peptidoglycan hydrolase processing. Membrane fatty acid changes
      correlated with increased membrane fluidity were observed. It seems likely that
      there are multiple genetic changes associated with the development of decreased
      telavancin susceptibility. The Tlv(DS) mutant showed some similar features to
      vancomycin-intermediate S. aureus and decreased daptomycin susceptibility
      strains, but also exhibited its own unique features. 

PMID- 23551250
TI  - Traditional and modern plant breeding methods with examples in rice (Oryza sativa
      L.).
AB  - Plant breeding can be broadly defined as alterations caused in plants as a result
      of their use by humans, ranging from unintentional changes resulting from the
      advent of agriculture to the application of molecular tools for precision
      breeding. The vast diversity of breeding methods can be simplified into three
      categories: (i) plant breeding based on observed variation by selection of plants
      based on natural variants appearing in nature or within traditional varieties;
      (ii) plant breeding based on controlled mating by selection of plants presenting
      recombination of desirable genes from different parents; and (iii) plant breeding
      based on monitored recombination by selection of specific genes or marker
      profiles, using molecular tools for tracking within-genome variation. The
      continuous application of traditional breeding methods in a given species could
      lead to the narrowing of the gene pool from which cultivars are drawn, rendering
      crops vulnerable to biotic and abiotic stresses and hampering future progress.
      Several methods have been devised for introducing exotic variation into elite
      germplasm without undesirable effects. Cases in rice are given to illustrate the
      potential and limitations of different breeding approaches. 

PMID- 23551251
TI  - Anion transporters and biological systems.
AB  - In this Account, we discuss the development of new lipid bilayer anion
      transporters based on the structure of anionophoric natural products (the
      prodigiosins) and purely synthetic supramolecular systems. We have studied the
      interaction of these compounds with human cancer cell lines, and, in general, the
      most active anion transporter compounds possess the greatest anti-cancer
      properties. Initially, we describe the anion transport properties of synthetic
      molecules that are based on the structure of the family of natural products known
      as the prodiginines. Obatoclax, for example, is a prodiginine derivative with an
      indole ring that is currently in clinical trials for use as an anti-cancer drug.
      The anion transport properties of the compounds were correlated with their
      toxicity toward small cell human lung cancer GLC4 cells. We studied related
      compounds with enamine moieties, tambjamines, that serve as active transporters.
      These molecules and others in this series could depolarize acidic compartments
      within GLC4 cells and trigger apoptosis. In a study of the variation of
      lipophilicity of a series of these compounds, we observed that, as log P
      increases, the anion transport efficiency reaches a peak and then decreases. In
      addition, we discuss the anion transport properties of series of synthetic
      supramolecular anion receptor species. We synthesized trisureas and thioureas
      based on the tren backbone, and found that the thiourea compounds effectively
      transport anions. Fluorination of the pendant phenyl groups in this series of
      compounds greatly enhances the transport properties. Similar to our earlier
      results, the most active anion transporters reduced the viability of human cancer
      cell lines by depolarizing acidic compartments in GLC4 cells and triggering
      apoptosis. In an attempt to produce simpler transporters that obey Lipinski's
      Rule of Five, we synthesized simpler systems containing a single urea or thiourea
      group. Once again the thiourea systems, and in particular a thiourea with a
      pendant indole group, transported anions efficiently. A series of related
      compounds containing a pendant trifluoromethyl group showed enhanced transport
      and significant anticancer properties. Researchers still need to determine of the
      exact mechanism of how these compounds depolarize acidic organelles within cancer
      cells. However, this work shows that these transporters based upon both natural
      products and purely synthetic supramolecular systems transport anions, depolarize
      acidic compartments within cancer cells and trigger apoptosis.

PMID- 23551252
TI  - Simple field device for measurement of dimethyl sulfide and
      dimethylsulfoniopropionate in natural waters, based on vapor generation and
      chemiluminescence detection.
AB  - A small, simple device was developed for trace analysis of dimethyl sulfide (DMS)
      and dimethylsulfoniopropionate (DMSP) in natural waters. These compounds are
      known to be the major sources of cloud condensation nuclei in the oceanic
      atmosphere and ideally should be measured onsite because of their volatility and
      instability. First, chemical and physical vapor generations were examined, and
      simple pressurizing by injection of 30 mL of air using a syringe was adopted.
      Pressurized headspace air above a 10 mL water sample was introduced to a
      detection cell as a result of the pressure differential and mixed with ozone to
      induce chemiluminescence. Although the measurement procedure was simple, the
      method was very sensitive: sharp peaks appeared within seconds for nanomolar
      levels of DMS, and the limit of detection was 0.02 nmol L(-1) (1 ng L(-1)).
      Although interference from methanethiol was significant, this was successfully
      addressed by adding a small amount of Cd(2+) before DMS vapor generation. DMSP
      was also measured after hydrolysis to DMS, as previously reported. Pond water and
      seawater samples were analyzed, and DMS was found in both types of sample,
      whereas DMSP was observed only in seawater. The DMS/DMSP data obtained using the
      developed method were compared with data obtained by purge/trap and gas
      chromatography-mass spectrometry, and the data from the two methods agreed, with
      good correlation (R(2) = 0.9956). The developed device is inexpensive, light (5
      kg), simple to use, can be applied in the field, and is sensitive enough for
      fresh- and seawater analysis. 

PMID- 23551253
TI  - Expression of the collagen adhesin ace by Enterococcus faecalis strain OG1RF is
      not repressed by Ers but requires the Ers box.
AB  - Expression of adhesin to collagen of Enterococcus faecalis (ace), a known
      virulence factor, is increased by environmental signals such as the presence of
      serum, high temperature, and bile salts. Currently, the enterococcal regulator of
      survival (Ers) of E. faecalis strain JH2-2 is the only reported repressor of ace.
      Here, we show that for strain OG1RF, Ers is not involved in the regulation of
      ace. Our data showed similar levels of ace expression by OG1RF and its Deltaers
      derivative in the presence of bile salts, serum, and high temperature. Using ace
      promoter-lacZ fusions and site-directed mutagenesis, we confirmed these results
      and further showed that, while the previously designated Ers box is important for
      increased expression from the ace promoter of OG1RF, the region responsible for
      the increase is bigger than the Ers box. In summary, these results indicate that,
      in strain OG1RF, Ers is not a repressor of ace expression. Although JH2-2 and
      OG1RF differ by six nucleotides in the region upstream of ace as well as in
      production of Fsr and gelatinase, the reason(s) for the difference in ace
      expression between JH2-2 and OG1RF and for increased ace expression in bile,
      serum and at 46  degrees C remain(s) to be determined.

PMID- 23551254
TI  - Transthyretin-binding activity of contaminants in blood from polar bear (Ursus
      maritimus) cubs.
AB  - We determined the transthyretin (TTR)-binding activity of blood-accumulating
      contaminants in blood plasma samples of approximately 4-months-old polar bear
      (Ursus maritimus) cubs from Svalbard sampled in 1998 and 2008. The TTR-binding
      activity was measured as thyroxine (T4)-like equivalents (T4-EQMeas). Our
      findings show that the TTR-binding activity related to contaminant levels was
      significantly lower (45%) in 2008 than in 1998 (mean +/- standard error of mean:
      1998, 2265 +/- 231 nM; 2008, 1258 +/- 170 nM). Although we cannot exclude a
      potential influence of between-year differences in capture location and cub body
      mass, our findings most likely reflect reductions of TTR-binding contaminants or
      their precursors in the arctic environment (e.g., polychlorinated biphenyls
      [PCBs]). The measured TTR-binding activity correlated positively with the cubs'
      plasma levels of hydroxylated PCBs (OH-PCBs). No such association was found
      between TTR-binding activity and the plasma levels of perfluoroalkyl substances
      (PFASs). The OH-PCBs explained 60 +/- 7% and 54 +/- 4% of the TTR-binding
      activity in 1998 and 2008, respectively, and PFASs explained <=1.2% both years.
      Still, almost half the TTR-binding activity could not be explained by the
      contaminants we examined. The considerable levels of TTR-binding contaminants
      warrant further effect directed analysis (EDA) to identify the contaminants
      responsible for the unexplained part of the observed TTR-binding activity.

PMID- 23551255
TI  - Ion distributions at the water/1,2-dichloroethane interface: potential of mean
      force approach to analyzing X-ray reflectivity and interfacial tension
      measurements.
AB  - We present X-ray reflectivity and interfacial tension measurements of the
      electrified liquid/liquid interface between two immiscible electrolyte solutions
      for the purpose of understanding the dependence of interfacial ion distributions
      on the applied electric potential difference across the interface. The aqueous
      phase contains alkali-metal chlorides, including LiCl, NaCl, RbCl, or CsCl, and
      the organic phase is a 1,2-dichloroethane solution of bis(triphenylphosphor
      anylidene) ammonium tetrakis(pentafluorophenyl)borate (BTPPATPFB). Selected data
      for a subset of electric potential differences are analyzed to determine the
      potentials of mean force for Li(+), Rb(+), Cs(+), BTPPA(+), and TPFB(-). These
      potentials of mean force are then used to analyze both X-ray reflectivity and
      interfacial tension data measured over a wide range of electric potential
      differences. Comparison of X-ray reflectivity data for strongly hydrated alkali
      metal ions (Li(+) and Na(+)), for which ion pairing to TPFB(-) ions across the
      interface is not expected, to data for weakly hydrated alkali-metal ions (Rb(+)
      and Cs(+)) indicates that the Gibbs energy of adsorption due to ion pairing at
      the interface must be small (<1 k(B)T per ion pair) for both the CsCl and RbCl
      samples. This paper demonstrates the applicability of the Poisson-Boltzmann
      potential of mean force approach to the analysis of X-ray reflectivity
      measurements that probe the nanoscale ion distribution and the consequences of
      these underlying distributions for thermodynamic studies, such as interfacial
      tension measurements, that yield quantities related to the integrated ion
      distribution.

PMID- 23551256
TI  - Infant temperament and childhood psychiatric disorder: longitudinal study.
AB  - BACKGROUND: Temperamental characteristics emerge early in life and can shape
      children's development, adjustment and behaviour. We aimed to investigate the
      association between early infant temperament and later childhood psychiatric
      disorder in a community sample. METHODS: This prospective, population-based study
      used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). In a
      sample of 7318 children, we investigated whether temperamental characteristics
      assessed at the ages of 6 months and 24 months are associated with an independent
      diagnosis of psychiatric disorder ascertained at age 7 years. RESULTS: After
      adjusting for confounders, temperamental characteristics assessed at 6 and 24
      months of age were associated with psychiatric disorder at age 7 years. In
      particular, intensity of emotional reaction at age 6 months was associated with
      later disorder (adjusted odds ratio = 1.56; 95% confidence interval 1.19, 2.04; P
      = 0.002). These associations were stronger in girls and in those children with
      high levels of intensity at both 6 and 24 months of age. CONCLUSIONS:
      Temperamental characteristics involving high levels of emotional intensity within
      the first year of life are longitudinally associated with psychiatric disorder in
      mid-childhood, suggesting that the roots of psychiatric disorder may, in some
      cases, lie very early in life.

PMID- 23551257
TI  - Arterial tissue regeneration for pediatric applications: inspiration from up-to
      date tissue-engineered vascular bypass grafts.
AB  - The need for a valid replacement for autologous tissues in vascular surgery has
      led to the development of tissue-engineered vascular grafts (TEVGs). Currently,
      only three kinds of TEVG have been used in clinical trials: synthetic scaffold
      based TEVGs, self-assembled grafts, and decellularized exogenous tissues. This
      review presents the current options in the construction of TEVG and the changes
      that have occurred in the design following the clinical experience while focusing
      on the potential for pediatric applications. The emerging trend in the field,
      which is also pertinent for pediatric applications, is a shift from the
      development of vascular analogues to implants composed of scaffolds with
      autologous cellular components. Designs of such implants are currently being fine
      tuned so that a natural, functional tissue can gradually take over the role of
      scaffolds to stimulate the host's regenerative capacity and maintain the
      physiological homeostasis.

PMID- 23551258
TI  - Progress toward the determination of correct classification rates in fire debris
      analysis.
AB  - Principal components analysis (PCA), linear discriminant analysis (LDA), and
      quadratic discriminant analysis (QDA) were used to develop a multistep
      classification procedure for determining the presence of ignitable liquid residue
      in fire debris and assigning any ignitable liquid residue present into the
      classes defined under the American Society for Testing and Materials (ASTM) E
      1618-10 standard method. A multistep classification procedure was tested by cross
      validation based on model data sets comprised of the time-averaged mass spectra
      (also referred to as total ion spectra) of commercial ignitable liquids and
      pyrolysis products from common building materials and household furnishings
      (referred to simply as substrates). Fire debris samples from laboratory-scale and
      field test burns were also used to test the model. The optimal model's true
      positive rate was 81.3% for cross-validation samples and 70.9% for fire debris
      samples. The false-positive rate was 9.9% for cross-validation samples and 8.9%
      for fire debris samples. 

PMID- 23551259
TI  - Features of evolutionarily conserved alternative splicing events between Brassica
      and Arabidopsis.
AB  - Alternative splicing (AS) generates multiple types of mRNA from a single type of
      pre-mRNA by differential intron splicing. It can result in new protein isoforms
      or down-regulation of gene expression by transcript decay. The evolutionary
      conservation of AS events in plants is largely unexplored and only a small number
      of AS events have been identified as conserved between divergent species. We
      performed a large-scale analysis of cDNA data from Brassica and Arabidopsis to
      identify and further characterize conserved AS events. We identified 537
      conserved AS events in 485 genes. Alternative donor and acceptor events are
      significantly overrepresented among conserved events, whereas intron retention
      and exon skipping events are underrepresented. Conserved AS events are
      significantly shorter, less likely to be in the 3'UTR, and they are enriched for
      genes whose products function in the chloroplast. AS modified a functional domain
      for about half of the genes with conserved events. We further characterized three
      genes with conserved AS events. This study identifies many AS events that are
      conserved between Brassica and Arabidopsis, revealing features of conserved AS
      events. Many of the conserved AS events may have important, but uncharacterized,
      functions.

PMID- 23551260
TI  - An investigation into the socioeconomic aspects of two major earthquakes in Iran.
AB  - An evaluation of the socioeconomic consequences of earthquakes is an essential
      part of the development of risk reduction and disaster management plans. However,
      these variables are not normally addressed sufficiently after strong earthquakes;
      researchers and relevant stakeholders focus primarily on the physical damage and
      casualties. The importance of the socioeconomic consequences of seismic events
      became clearer in Iran after the Bam earthquake on 26 December 2003, as
      demonstrated by the formulation and approval of various laws and ordinances. This
      paper reviews the country's regulatory framework in the light of the
      socioeconomic aspects of two major and destructive earthquakes: in Manjil-Rudbar
      in 1990, and in Bam in 2003. The results take the form of recommendations and
      practical strategies for incorporating the socioeconomic dimensions of
      earthquakes in disaster risk management planning. The results presented here can
      be applied in other countries with similar conditions to those of Iran in order
      to improve public preparedness and risk reduction.

PMID- 23551261
TI  - Recognition of goblet cells upon endocytoscopy indicates the presence of gastric
      intestinal metaplasia.
AB  - BACKGROUND: Gastric intestinal metaplasia (IM) is considered precancerous and is
      difficult to differentiate upon endoscopy. Endocytoscopy enables observation at a
      cellular level for focused biopsy. The present study examined the use of
      endocytoscopy for recognition of gastric IM. PATIENTS AND METHODS: Patients with
      a history of gastric IM were recruited. We first carried out narrow band imaging
      (NBI) endoscopy to look for suspicious areas of gastric IM. A prototype
      endocytoscope with a magnification of 450* was used to re-examine these areas.
      Areas examined were biopsied for histological comparison. Presence of goblet
      cells was considered as representative of IM upon endocytoscopy. RESULTS: Twenty
      patients were recruited with NBI demonstrating 102 suspicious lesions of gastric
      IM. Mean age of patients was 53.9 +/- 7.6 years. Upon histology, 72 biopsies were
      confirmed as gastric IM, 15 showed IM and low-grade dysplasia, whereas 15were
      diagnosed as chronic gastritis. Endocytoscopy image quality was significantly
      better for areas of IM as compared to gastritis (P < 0.05; OR 21.7 [95% CI 4.5
      105.9]). The presence of goblet cells upon endocytoscopy achieved a diagnostic
      accuracy of 0.86 for gastric IM. Receiver operator characteristics curve achieved
      an area under curve of 0.8 with the presence of goblet cells under endocytoscopy
      as compared to 0.64 for NBI alone. CONCLUSIONS: Presence of goblet cells upon
      endocytoscopy indicates a diagnosis of gastric IM. Image quality of
      endocytoscopy, however, is suboptimal. Further developments in endocytoscopy
      should focus on image quality and staining methods to enhance differentiation
      between IM, dysplasia and early gastric cancer.

PMID- 23551264
TI  - Biodegradable stents after lung transplantation.

PMID- 23551265
TI  - Painful cutaneous nodules and ulcerations in a 68-year-old woman with rheumatoid
      arthritis.

PMID- 23551266
TI  - Investigation of the mechanism for the preparation of 6-phenyl-2,4
      dioxotetrahydropyrans by the potassium carbonate promoted condensation between
      acetoacetate esters and benzaldehyde.
AB  - Treatment of benzaldehyde and an acetoacetate ester with potassium carbonate in
      an alcohol solvent proceeds via gamma-C-alkylation rather than alpha-C-alkylation
      resulting in the formation of 6-phenyl-2,4-dioxotetrahydropyran. Based upon
      results from deuterium exchange experiments, carbon-13 labeling experiments, (1)H
      NMR monitoring studies, and reactivity studies, our proposed mechanism for this
      reaction involves deprotonation at the alpha-carbon, intramolecular proton
      transfer to form a gamma-anion, addition of the resulting gamma-anion to the
      carbonyl carbon of benzaldehyde, and intramolecular transesterification.

PMID- 23551262
TI  - Characteristics of IL-17 induction by Schistosoma japonicum infection in C57BL/6
      mouse liver.
AB  - Schistosomiasis japonica is a severe tropical disease caused by the parasitic
      worm Schistosoma japonicum. Among the most serious pathological effects of S.
      japonicum infection are hepatic lesions (cirrhosis and fibrosis) and portal
      hypertension. Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in
      the pathogenesis of many inflammatory and infectious conditions, including
      schistosomiasis. We infected C57BL/6 mice with S. japonicum and isolated
      lymphocytes from the liver to identify cell subsets with high IL-17 expression
      and release using flow cytometry and ELISA. Expression and release of IL-17 was
      significantly higher in hepatic lymphocytes from infected mice compared with
      control mice in response to both non-specific stimulation with anti-CD3
      monoclonal antibody plus/anti-CD28 monoclonal antibody and PMA plus ionomycin. We
      then compared IL-17 expression in three hepatic T-cell subsets, T helper, natural
      killer T and gammadeltaT cells, to determine the major source of IL-17 during
      infection. Interleukin-17 was induced in all three subsets by PMA + ionomycin,
      but gammadeltaT lymphocytes exhibited the largest increase in expression. We then
      established a mouse model to further investigate the role of IL-17 in
      granulomatous and fibrosing inflammation against parasite eggs. Reducing IL-17
      activity using anti-IL-17A antibodies decreased infiltration of inflammatory
      cells and collagen deposition in the livers of infected C57BL/6 mice. The serum
      levels of soluble egg antigen (IL)-specific IgGs were enhanced by anti-IL-17A
      monoclonal antibody blockade, suggesting that IL-17 normally serves to suppress
      this humoral response. These findings suggest that gammadeltaT cells are the most
      IL-17-producing cells and that IL-17 contributes to granulomatous inflammatory
      and fibrosing reactions in S. japonicum-infected C57BL/6 mouse liver.

PMID- 23551267
TI  - Predicting positive food challenges in children sensitised to peanuts/tree nuts.
AB  - BACKGROUND: Children with atopic diseases in early life are frequently found with
      positive IgE tests to peanuts/tree nuts without a history of previous ingestion.
      We aimed to identify risk factors for reactions to nuts at first introduction.
      METHODS: A retrospective case-note and database analysis was performed.
      Recruitment criteria were: patients aged 3-16 yr who had a standardized food
      challenge to peanut and/or tree nuts due to sensitisation to the peanut/tree nut
      (positive spIgE or SPT) without previous consumption. A detailed assessment was
      performed of factors relating to food challenge outcome with univariate and
      multivariate logistic regression analysis. RESULTS: There were 98 food challenges
      (47 peanut, 51 tree nut) with 29 positive, 67 negative and 2 inconclusive
      outcomes. A positive maternal history of allergy and a specific IgE >5 kU/l were
      strongly associated with a significantly increased risk of a positive food
      challenge (OR 3.73; 95% CI 1.31-10.59; p = 0.013 and OR 3.35; 95% CI 1.23-9.11; p
      = 0.007, respectively). Adjusting for age, a three year-old with these criteria
      has a 67% probability of a positive challenge. There was no significant
      association between types of peanut/tree nut, other food allergies, atopic
      conditions or severity of previous food reactions and positive challenges.
      CONCLUSIONS: We have demonstrated an association between the presence of maternal
      atopic history and a specific IgE >5 kU/l, with a significant increase in the
      likelihood of a positive food challenge. Although requiring further prospective
      validation these easily identifiable components should be considered when
      deciding the need for a challenge.

PMID- 23551268
TI  - Work engagement and occupational stress in nurses and other healthcare workers:
      the role of organisational and personal factors.
AB  - AIMS AND OBJECTIVES: The aims of this study were to: (1) identify the role of
      organisational and personal factors in predicting work engagement in healthcare
      workers and (2) compare work engagement and occupational stress perceptions of
      healthcare professional categories. BACKGROUND: Healthcare professionals, with
      particular regard to nurses, are exposed to several job stressors that can
      adversely affect both their mental and physical health and also decrease work
      engagement. Work engagement can be considered as the positive opposite of
      burnout, and it is characterised by energy, involvement and professional
      efficacy. DESIGN: A cross-sectional survey research was conducted with self
      report questionnaires. METHODS: The Maslach Burnout Inventory-General Survey, the
      Areas of Worklife Scale and four scales from the Occupational Stress Indicator
      were administered to a sample of 198 hospital staff (registered nurses, nurse
      aides, physicians and physiotherapists), of which 110 participated in the study.
      RESULTS: The most significant predictors of energy were workload, mental health
      and job satisfaction; the best predictors of involvement were community,
      workload, mental health and job satisfaction; professional efficacy was best
      predicted by values and job satisfaction. In relation to the second aim,
      physiotherapists had the highest levels of occupational stress and disengagement
      from their work, while nurse aides were the most work-engaged and job-satisfied
      professional category, with positive perceptions of the work environment.
      CONCLUSIONS: Both organisational and personal factors were found to be
      significantly associated with work engagement. In this study, physiotherapists
      were the category with the highest risk of work-related psychological problems,
      whereas nurse aides had the lowest risk. RELEVANCE TO CLINICAL PRACTICE:
      Interventions aimed at improving clinical practice and psychological health of
      nurses and hospital staff should focus on workload, workers' personal
      expectations and job satisfaction.

PMID- 23551269
TI  - Vitamin D deficiency in adolescents living at high latitudes: are we missing
      something in the recommendations?

PMID- 23551270
TI  - Experience with a novel retrograde wiring technique for coronary chronic total
      occlusion.
AB  - OBJECTIVES: We report our evaluation of a novel retrograde wiring technique known
      as the Rendezvous method. BACKGROUND: Different strategies of retrograde
      approaches can be used to improve the success rate of recanalization of coronary
      chronic total occlusion (CTO). We previously introduced the Rendezvous technique
      as an alternative final step for a retrograde CTO procedure. METHODS: From July
      2007 to May 2010, 20 CTO patients were treated in two medical centers using the
      Rendezvous method, which is an alternative to the conventional final
      externalization method to complete the retrograde CTO procedure. It involves
      crossing of the guidewire through the CTO segment using 2 microcatheters.
      RESULTS: The majority of the CTO sites were in the proximal right coronary artery
      (50.0%). Most of the lesions had mild to moderate calcification (95.0%) and
      revealed an abrupt stump with a side branch at the occlusion site. The lesion
      length of the occlusion was relatively long (median 27.6 mm; range of 7.1-87.3
      mm). No adverse cardiac events occurred during hospitalization. CONCLUSION: The
      Rendezvous method used during the retrograde approach can be performed as an
      alternative to the conventional "externalization method" after the guidewire and
      microcatheter have crossed the occluded proximal segment into the opposite
      guiding catheter.

PMID- 23551271
TI  - A novel, web-based, psychological intervention for people with psoriasis: the
      electronic Targeted Intervention for Psoriasis (eTIPs) study.
AB  - BACKGROUND: Psychological morbidity and reduced quality of life are common and
      linked with nonadherence to medication in psoriasis. Access to psychological
      therapy is often poor with long waiting times. Cognitive behavioural therapy
      (CBT) is a well-accepted therapy for psychological disorders and is particularly
      effective when tailored to address condition-specific concerns. OBJECTIVES: To
      determine whether an electronic CBT intervention for Psoriasis (eTIPs) would
      reduce distress, improve quality of life and clinical severity in patients with
      psoriasis. METHODS: This was a wait-list, randomized trial of immediate
      intervention vs. usual care. Self-assessed psoriasis severity (Self-Administered
      Psoriasis Area and Severity Index), distress (Hospital Anxiety and Depression
      Scale) and quality of life (Dermatology Life Quality Index) were measured before
      and after intervention. Analysis was based on complete cases and all cases using
      multiple imputation to substitute missing values. RESULTS: Anxiety scores between
      groups were significantly reduced (P < 0.05) for complete cases only; the mean
      (SD) scores were: intervention 7.6 (3.6) at baseline and 6.1 (3.5) at follow-up
      vs. control 8.3 (3.5) at baseline and after intervention 8.1 (4.4) (P = 0.004).
      Depression scores did not change; the experimental group scores at baseline were
      5.0 (4.2) and after intervention 4.0 (3.7) vs. control group at baseline 5.2
      (3.4) and after intervention 4.9 (3.8). Psoriasis severity scores did not change:
      baseline scores for the experimental group were 7.5 (6.0) and after intervention
      6.5 (8.5) vs. the control group before 8.3 (6.3) and after 7.6 (6.1) (not
      significant). Quality-of-life scores improved in both analyses (P < 0.05); the
      intervention group scores before were 6.6 (4.2) and after intervention 5.0 (5.1)
      vs. control before 7.4 (4.4) and after intervention 7.7 (4.5) (P = 0.042).
      CONCLUSIONS: This first online CBT intervention for people with skin disease
      showed improvement in anxiety and quality of life in patients with psoriasis. The
      results are limited by the large amount of missing data and, at this stage,
      online delivery cannot substitute for established methods of delivery for CBT.

PMID- 23551272
TI  - From gene to brain to behavior: schizophrenia-associated variation in AMBRA1
      alters impulsivity-related traits.
AB  - Recently, genome-wide association between schizophrenia and an intronic variant
      in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach
      in adult healthy subjects, risk allele carriers showed a higher medial prefrontal
      cortex blood oxygen level-dependent (BOLD) response during a flanker task
      examining motor inhibition as an aspect of impulsivity. To test whether this
      finding can be expanded to further aspects of impulsivity, we analysed the
      effects of the rs11819869 genotype on impulsivity-related traits on a behavioral,
      temperament and neural level in a large sample of healthy adolescents. We
      consider this reverse genetic approach specifically suited for use in a healthy
      adolescent sample, as these individuals comprise those who will eventually
      develop mental disorders in which impulsivity is implicated. Healthy adolescents
      from the IMAGEN study were included in the neuropsychological analysis (n = 848)
      and a functional magnetic resonance imaging (fMRI) task (n = 512). Various
      aspects of impulsivity were assessed using the Temperament and Character
      Inventory-Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition
      Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the
      fMRI paradigm. On a behavioral level, increased delay aversion was observed in
      risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD
      response in an orbito-frontal target region during the SST, which declined to
      trend status after Family Wise Error correction. Our findings support the
      hypothesis that the schizophrenia-related risk variant of rs11819869 is involved
      in various aspects of impulsivity, and that this involvement occurs on a
      behavioral as well as an imaging genetics level. 

PMID- 23551273
TI  - Predictors of large and small for gestational age birthweight in offspring of
      women with gestational diabetes mellitus.
AB  - AIM: To identify predictors of large and small for gestational age in women with
      gestational diabetes mellitus. METHODS: A retrospective audit of clinical data
      analysed for singleton births in women diagnosed with gestational diabetes by
      Australasian Diabetes in Pregnancy Society guidelines from 1994 to 2009.
      Exclusions were: incomplete data, delivered at < 36 weeks gestation and/or last
      recorded weight > 4 weeks pre-delivery. We assessed: pre-pregnancy BMI,
      ethnicity, total maternal weight gain, weight gain before and after treatment
      initiation for gestational diabetes, HbA(1c) at gestational diabetes presentation
      and treatment modality (diet or insulin) and smoking. Birthweight was assessed
      using customized percentile charts (large for gestational age > 90th; small for
      gestational age < 10th percentile). Multiple regression analyses were undertaken;
      statistical significance was p < 0.05. RESULTS: There were 1695 women first seen
      at (mean +/- sd) 28.1 +/- 5.3 weeks gestation (range 6-39). Ethnic mix was South
      East Asian 36.7%, Middle Eastern 27.6%, European 22.4%, Indian/Pakistani 8.6%,
      Samoan 1.9%, African 1.5% and Maori 1.1%. Therapy was diet 69.1% and insulin
      30.9%. Mean total weight gain was 12.3 +/- 6.1 kg, the majority (10.6 +/- 6.0
      kg), gained before dietary intervention. There were 7.9% small for gestational
      age and 15.2% large for gestational age births. Significant independent large for
      gestational age predictors were: weight gain before intervention, pre-pregnancy
      BMI, weight gain after intervention and treatment type, but not HbA1c or smoking.
      Significant small for gestational age predictors were: weight gain before
      intervention, weight gain after intervention, but not pre-pregnancy BMI, HbA(1c)
      or smoking. CONCLUSION: Conventional treatment for gestational diabetes mellitus
      concentrates on management of blood glucose levels. The trends identified here
      emphasize the need to also address pregnancy weight gain stratified by pre
      pregnancy BMI.

PMID- 23551274
TI  - The evolving male: spinner dolphin (Stenella longirostris) ecotypes are divergent
      at Y chromosome but not mtDNA or autosomal markers.
AB  - The susceptibility of the Y chromosome to sexual selection may make this
      chromosome an important player in the formation of reproductive isolating
      barriers, and ultimately speciation. Here, we investigate the role of the Y
      chromosome in phenotypic divergence and reproductive isolation of spinner dolphin
      (Stenella longirostris) ecotypes. This species contains six known ecotypes
      (grouped into four subspecies) that exhibit striking differences in morphology,
      habitat and mating system, despite having adjacent or overlapping ranges and
      little genetic divergence at previously studied mtDNA and autosomal markers. We
      examined the phylogeographic structure for all six ecotypes across the species
      range (n = 261, 17 geographic locations) using DNA sequences from three Y
      chromosome markers, two maternally inherited mitochondrial (mtDNA) markers, and a
      biparentally inherited autosomal intron. mtDNA and autosomal analyses revealed
      low divergence (most Phi(ST) values <0.1) between ecotypes and geographic
      regions, concordant with previous studies. In contrast, Y intron analyses
      revealed fixed differences amongst the three most phenotypically divergent
      groups: S. l. longirostris vs. S. l. roseiventris vs. combined S. l.
      orientalis/S. l. centroamericana/Tres Marias ecotypes). Another ecotype
      (whitebelly), previously postulated to be a hybrid between the two phenotypically
      most divergent ecotypes, had Y haplotypes from both putative parent ecotypes,
      supporting a hybrid designation. Reduced introgression of the Y chromosome has
      previously been observed in other organisms ranging from insects to terrestrial
      mammals, and here we demonstrate this phenomenon in a marine mammal with high
      dispersal capabilities. These results indicate that reduced introgression of the
      Y chromosome occurs in a wide taxonomic range of organisms and support the
      growing body of evidence that rapid evolution of the Y chromosome is important in
      evolutionary diversification.

PMID- 23551275
TI  - Putative cationic cell-wall-bound peroxidase homologues in Arabidopsis, AtPrx2,
      AtPrx25, and AtPrx71, are involved in lignification.
AB  - The final step of lignin biosynthesis, which is catalyzed by a plant peroxidase,
      is the oxidative coupling of the monolignols to growing lignin polymers. Cationic
      cell-wall-bound peroxidase (CWPO-C) from poplar callus is a unique enzyme that
      has oxidative activity for both monolignols and synthetic lignin polymers. This
      study shows that putative CWPO-C homologues in Arabidopsis , AtPrx2, AtPrx25, and
      AtPrx71, are involved in lignin biosynthesis. Analysis of stem tissue using the
      acetyl bromide method and derivatization followed by the reductive cleavage
      method revealed a significant decrease in the total lignin content of ATPRX2 and
      ATPRX25 deficient mutants and altered lignin structures in ATPRX2, ATPRX25, and
      ATPRX71 deficient mutants. Among Arabidopsis peroxidases, AtPrx2 and AtPrx25
      conserve a tyrosine residue on the protein surface, and this tyrosine may act as
      a substrate oxidation site as in the case of CWPO-C. AtPrx71 has the highest
      amino acid identity with CWPO-C. The results suggest a role for CWPO-C and CWPO-C
      like peroxidases in the lignification of vascular plant cell walls. 

PMID- 23551276
TI  - In vivo evaluation of the iPex and Root ZX electronic apex locators using various
      irrigants.
AB  - AIM: To evaluate in vivo the performance of the iPex and Root ZX electronic apex
      locators (EALs) in the presence of several irrigant solutions: 2.5% sodium
      hypochlorite (NaOCl) and 2% chlorhexidine (CHX). METHODOLOGY: Thirty-two single
      rooted human teeth that were scheduled for extraction were selected. Teeth with
      metallic restorations, fractures, root resorption, pulp necrosis or open apices
      were not included The working length (WL) was determined electronically for the
      root canals with the iPex and Root ZX EALs in the presence of two different
      irrigant solutions, 2.5% NaOCl and 2% CHX. After the teeth had been extracted, a
      size 10 K-file was used to determine the reference working length (RWL), which
      was established at 0.5 mm short of the major foramen. In each case, the RWL was
      subtracted from the electronic measurements. Positive values indicated electronic
      measurements that exceeded the RWL (long measurements), whereas negative values
      indicated measurements that were short of the RWL. The values obtained with the
      different irrigants and EALs were compared using the paired t-test. Significance
      was set at P < 0.05. RESULTS: The accuracy of the iPex nor Root ZX EAL was not
      affected by 2.5% NaOCl or 2% CHX (P > 0.05). However, significant differences
      were observed between the readings of the iPex and Root ZX, irrespective of
      whether 2.5% NaOCl or 2% CHX was used as the irrigant (P < 0.05). The iPex was
      less accurate than the Root ZX in determining the RWL. CONCLUSIONS: The accuracy
      of neither the iPex nor Root ZX EAL was affected by the irrigant used. However,
      the iPex was less accurate than the Root ZX in determining the RWL both for 2.5%
      NaOCl and for 2% CHX.

PMID- 23551278
TI  - Fever, nodulobullous eruption and swollen ears.

PMID- 23551279
TI  - The use of scale-invariance feature transform approach to recognize and retrieve
      incomplete shoeprints.
AB  - Shoeprints left at the crime scene provide valuable information in criminal
      investigation due to the distinctive patterns in the sole. Those shoeprints are
      often incomplete and noisy. In this study, scale-invariance feature transform is
      proposed and evaluated for recognition and retrieval of partial and noisy
      shoeprint images. The proposed method first constructs different scale spaces to
      detect local extrema in the underlying shoeprint images. Those local extrema are
      considered as useful key points in the image. Next, the features of those key
      points are extracted to represent their local patterns around key points. Then,
      the system computes the cross-correlation between the query image and each
      shoeprint image in the database. Experimental results show that full-size prints
      and prints from the toe area perform best among all shoeprints. Furthermore, this
      system also demonstrates its robustness against noise because there is a very
      slight difference in comparison between original shoeprints and noisy shoeprints.

PMID- 23551277
TI  - The synthesis and pharmacological evaluation of adamantane-derived indoles:
      cannabimimetic drugs of abuse.
AB  - Two novel adamantane derivatives, adamantan-1-yl(1-pentyl-1H-indol-3-yl)methanone
      (AB-001) and N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide (SDB-001), were
      recently identified as cannabimimetic indoles of abuse. Conflicting anecdotal
      reports of the psychoactivity of AB-001 in humans, and a complete dearth of
      information about the bioactivity of SDB-001, prompted the preparation of AB-001,
      SDB-001, and several analogues intended to explore preliminary structure-activity
      relationships within this class. This study sought to elucidate which structural
      features of AB-001, SDB-001, and their analogues govern the cannabimimetic
      potency of these chemotypes in vitro and in vivo. All compounds showed similar
      full agonist profiles at CB1 (EC50 = 16-43 nM) and CB2 (EC50 = 29-216 nM)
      receptors in vitro using a FLIPR membrane potential assay, with the exception of
      SDB-002, which demonstrated partial agonist activity at CB2 receptors. The
      activity of AB-001, AB-002, and SDB-001 in rats was compared to that of Delta(9)
      tetrahydrocannabinol (Delta(9)-THC) and cannabimimetic indole JWH-018 using
      biotelemetry. SDB-001 dose-dependently induced hypothermia and reduced heart rate
      (maximal dose 10 mg/kg) with potency comparable to that of Delta(9)
      tetrahydrocannabinol (Delta(9)-THC, maximal dose 10 mg/kg), and lower than that
      of JWH-018 (maximal dose 3 mg/kg). Additionally, the changes in body temperature
      and heart rate affected by SDB-001 are of longer duration than those of Delta(9)
      THC or JWH-018, suggesting a different pharmacokinetic profile. In contrast, AB
      001, and its homologue, AB-002, did not produce significant hypothermic and
      bradycardic effects, even at relatively higher doses (up to 30 mg/kg), indicating
      greatly reduced potency compared to Delta(9)-THC, JWH-018, and SDB-001. 

PMID- 23551280
TI  - Characteristics and direct costs of academic pediatric subspecialty outpatient no
      show events.
AB  - BACKGROUND: Clinic no shows (NS) create a lost opportunity for provider-patient
      interaction and impose a financial burden to the healthcare system and on
      society. We aimed to: (1) to determine the clinical and demographic factors
      associated with increased NS rates at a children's hospital's subsubspecialty
      clinics and (2) to estimate the direct institutional financial costs associated
      with NS events. METHODS: A comprehensive database was generated from all clinic
      encounters for 15 subspecialty outpatient clinics (five surgical and 10 medical)
      between September 12, 2005 and December 30, 2010. Multivariate logistic
      regressions were performed to identify the variables associated with NS events.
      Direct costs of NS events were estimated using annual revenue for each clinic.
      RESULTS: A total of 284,275 encounters and 17,024 NS events were available for
      analysis. Public insurance coverage (Medicaid and Title V), compared to private
      insurance or self-pay status, was associated with an increased likelihood NS (OR
      2.19, 95% CI 2.10-2.28, p < 0.0005 for Medicaid; OR 1.56, 95% CI 1.50-1.62, p <
      0.0005 for Title V). Compared to patients 21-30 years of age, patients <12 years
      (OR 2.08, 95% CI 1.77-2.45, p < 0.0005) had increased likelihood of NS. Scheduled
      visits with medical subspecialists were more likely than surgical subspecialty
      visits to result in a NS (OR 1.69, 95% CI 1.63-1.75, p < 0.0005). The predicted
      annualized lost revenue associated with NS visits was estimated at $730,000 from
      the 15 clinics analyzed, approximately $210 per NS event. CONCLUSION: Pediatric
      subspecialty NS events are common, costly, and potentially preventable.

PMID- 23551281
TI  - Contrasting patterns of viral load response in transplant recipients with BK
      polyomavirus DNAemia on leflunomide therapy.
AB  - BACKGROUND: Reduction in immunosuppression is considered the therapy of proven
      benefit for BKV infection in renal transplantation, but the use of leflunomide
      has also been reported. It was observed at this center that the patterns of viral
      load response while on leflunomide appear to fall into two distinct types.
      METHODS: Medical records of 22 kidney and kidney-pancreas recipients at a single
      center who received leflunomide therapy for BKV DNAemia were reviewed.
      Information was collected on demographics, BKV viral loads, other antiviral
      therapy, immunosuppressive drug levels and doses, adverse effects, and graft and
      patient outcomes. RESULTS: Eighteen of 22 cleared BKV viremia, and 12 of 22 had
      preserved allograft function; only two graft losses occurred in the screening era
      among leflunomide-treated patients. Two patterns of viral load reduction were
      observed, termed the "smooth" and the "zigzag" pattern, which differed in mean
      time to clear of BKV DNA (2.9 vs. 19.5 months, p = 0.0073). Graft preservation
      was correlated with lower serum creatinine (SCr) at the start of leflunomide
      therapy. CONCLUSIONS: Long courses and "zigzag" fluctuations in viral load can
      occur in patients who eventually clear BKV on leflunomide with preserved
      allograft function. Intermittent increases in viral load do not necessarily
      portend therapeutic failure. Although the utility of leflunomide is still debated
      in the transplant community, this information may be useful to clinicians who
      choose to use it in selected patients.

PMID- 23551283
TI  - Spinal cord stimulation in 2020.

PMID- 23551284
TI  - Neurotech report.

PMID- 23551282
TI  - Feasibility for mapping cartilage t1 relaxation times in the distal
      metacarpus3/metatarsus3 of thoroughbred racehorses using delayed gadolinium
      enhanced magnetic resonance imaging of cartilage (dGEMRIC): normal cadaver study.
AB  - Osteoarthritis of the metacarpo/metatarsophalangeal joints is one of the major
      causes of poor performance in horses. Delayed gadolinium-enhanced magnetic
      resonance imaging of cartilage (dGEMRIC) may be a useful technique for
      noninvasively quantifying articular cartilage damage in horses. The purpose of
      this study was to describe dGEMRIC characteristics of the distal
      metacarpus3/metatarsus3 (Mc3/Mt3) articular cartilage in 20 cadaver specimens
      collected from normal Thoroughbred horses. For each specimen, T1 relaxation time
      was measured from scans acquired precontrast and at 30, 60, 120, and 180 min post
      intraarticular injection of Gd-DTPA(2-) (dGEMRIC series). For each scan, T1
      relaxation times were calculated using five regions of interest (sites 1-5) in
      the cartilage. For all sites, a significant decrease in T1 relaxation times
      occurred between precontrast scans and 30, 60, 120, and 180 min scans of the
      dGEMRIC series (P < 0.0001). A significant increase in T1 relaxation times
      occurred between 60 and 180 min and between 120 and 180 min post Gd injection for
      all sites. For sites 1-4, a significant increase in T1 relaxation time occurred
      between 30 and 180 min postinjection (P < 0.05). Sites 1-5 differed significantly
      among one another for all times (P < 0.0001). Findings from this cadaver study
      indicated that dGEMRIC using intraarticular Gd-DTPA(2-) is a feasible technique
      for measuring and mapping changes in T1 relaxation times in equine
      metacarpo/metatarsophalangeal joint cartilage. Optimal times for postcontrast
      scans were 60-120 min. Future studies are needed to determine whether these
      findings are reproducible in live horses. 

PMID- 23551285
TI  - Science times.

PMID- 23551286
TI  - The dream of a future world.

PMID- 23551288
TI  - Probabilistic cost-benefit analysis of disaster risk management in a development
      context.
AB  - Limited studies have shown that disaster risk management (DRM) can be cost
      efficient in a development context. Cost-benefit analysis (CBA) is an evaluation
      tool to analyse economic efficiency. This research introduces quantitative,
      stochastic CBA frameworks and applies them in case studies of flood and drought
      risk reduction in India and Pakistan, while also incorporating projected climate
      change impacts. DRM interventions are shown to be economically efficient, with
      integrated approaches more cost-effective and robust than singular interventions.
      The paper highlights that CBA can be a useful tool if certain issues are
      considered properly, including: complexities in estimating risk; data dependency
      of results; negative effects of interventions; and distributional aspects. The
      design and process of CBA must take into account specific objectives, available
      information, resources, and the perceptions and needs of stakeholders as
      transparently as possible. Intervention design and uncertainties should be
      qualified through dialogue, indicating that process is as important as numerical
      results.

PMID- 23551289
TI  - Solvent cage effects: basis of a general mechanism for efficient
      chemiluminescence.
AB  - The induced decomposition of 1,2-dioxetanes results in the efficient formation of
      singlet-excited carbonyl compounds. This transformation has been assumed to
      involve two sequential electron-transfer steps, and the viscosity dependence of
      the chemiexcitation efficiency (solvent cage effect) has been considered as
      evidence for the occurrence of an intermolecular electron back-transfer, despite
      the very high chemiexcitation quantum yields observed. However, all other
      chemiluminescent reactions assumed to occur according to the entirely
      intermolecular mechanism, referred to as CIEEL, are inefficient, except for the
      peroxyoxalate system. Therefore, we have investigated the solvent cage effect on
      the singlet quantum yields in both the induced decomposition of 1,2-dioxetanes
      and the peroxyoxalate reaction. Analysis of the viscosity effect observed for
      both systems, using a collisional as well as a free-volume model, indicates a
      very distinct behavior, which was interpreted as the occurrence of intramolecular
      chemiexcitation in the induced 1,2-dioxetane decomposition. We propose a general
      mechanism for efficient chemiluminescence in which the required electron back
      transfer and C-C bond cleavage are concerted and compete with conformational
      changes that compromise the chemiexcitation. This mechanism is in agreement with
      both experimental and theoretical data available on the induced 1,2-dioxetane
      decomposition as well as with the high quantum efficiency of this transformation.

PMID- 23551290
TI  - Analysing policy interventions to prohibit over-the-counter antibiotic sales in
      four Latin American countries.
AB  - OBJECTIVES: To describe and evaluate policies implemented in Chile, Colombia,
      Venezuela and Mexico (1995-2009) to prohibit antibiotic OTC sales and explore
      limitations in available data. METHODS: We searched and analysed legislation,
      grey literature and peer-reviewed publications on regulatory interventions and
      implementation strategies to enforce prohibition of OTC antibiotic sales. We also
      assessed the impact using private sector retail sales data of antibiotics
      studying changes in level and consumption trends before and after the policy
      change using segmented time series analysis. Finally, we assessed the
      completeness and data quality through an established checklist to test the
      suitability of the data for analysis of the interventions. RESULTS: Whereas Chile
      implemented a comprehensive package of interventions to accompany regulation
      changes, Colombia's reform was limited to the capital district and Venezuela's
      limited to only some antibiotics and without awareness campaigns. In Mexico, no
      enforcement was enacted. The data showed a differential effect of the
      intervention among the countries studied with a significant change in level of
      consumption in Chile (-5.56 DID) and in Colombia (-1.00DID). In Venezuela and
      Mexico, no significant change in level and slope was found. Changes in population
      coverage were identified as principal limitations of using sales data for
      evaluating the reform impact. CONCLUSION: Retail sales data can be useful when
      assessing policy impact but should be supplemented by other data sources such as
      public sector sales and prescription data. Implementing regulatory enforcement
      has shown some impact, but a sustainable, concerted approach will be needed to
      address OTC sales in the future.

PMID- 23551291
TI  - Postnatal steroids in extremely low birth weight infants: betamethasone or
      hydrocortisone?
AB  - AIM: To compare the efficacy and tolerance of betamethasone (BTM) and
      hydrocortisone (HC) in weaning extremely low birth weight (ELBW) infants with
      bronchopulmonary dysplasia (BPD) from the ventilator. METHODS: Monocentric,
      retrospective, cohort analysis based on prospective, standardized collection of
      data between 2005 and 2011 in ELBW receiving postnatal steroids (PS) after the
      second week of life. We used BTM for the first 4 years, and thereafter HC. We
      compared extubation rates, growth, glycaemia and blood pressure. RESULTS: Sixty
      seven infants received PS: 35 BTM and 32 HC. Most infants (83% BTM vs. 72% HC)
      were extubated during treatment (p = 0.281). During PS, the need for insulin was
      similar. Mean arterial blood pressure was similar at day 3 of PS, but was
      significantly lower in infants treated by BTM 30 days after the end of treatment.
      The z-scores for body weight and head circumference indicated significantly
      greater loss in BTM than HC group. This persisted only for body weight after
      adjustment for differences in energy intake and corticosteroid dose. CONCLUSION:
      Our study suggests that HC may be as efficient as BTM in facilitating the
      extubation of ELBW infants, without short-term adverse effects. Blood pressure
      monitoring and investigation of long-term neurodevelopment are nevertheless
      needed.

PMID- 23551292
TI  - Priapism associated with lumbar stenosis in a dog.
AB  - Priapism, a persistent long-lasting involuntary erection of the penis, is
      uncommon in dogs. In this report, the case of a 13-year-old male Pointer,
      referred to our services due to persistent exposition of the penis, is described.
      This condition was consecutive to an intermittent priapism situation lasting for
      several days, which has been initially attributed to the inflammation and
      haematoma associated with a perianal bite. The owners became unable to retract
      the penis into the prepuce. At presentation, the dog was anorectic for 48 h,
      intolerant to manipulation, and showed poor body condition and unsteady
      locomotion. During physical evaluation, a marked engorgement of the local vessels
      in the prepuce and penis was found. An abdominal X-ray was asked under the
      suspicion of a neurogenic origin for the clinical situation, which showed
      evidences of spondylosis. After discussion of the clinical condition, the owners
      asked for euthanasia. The necropsy confirmed the engorgement of the regional
      vessels deriving from the pudendal arteries and blood accumulation within all the
      cavernous spaces, accompanied by congestion and thrombosis within the erectile
      structures of the penis. No significant changes were observed in the pelvic
      organs that could be at the origin of priapism. The lumbar-sacral spinal regions
      were carefully inspected and evidenced signs of L7-S1 stenosis due to
      spondylosis. The case presented herein is a rare situation of priapism of
      neurogenic origin in a dog. Necropsy findings suggest that it was consecutive to
      cauda equina compression due to lumbar spinal stenosis. 

PMID- 23551293
TI  - The downward occupational mobility of internationally educated nurses to domestic
      workers.
AB  - Despite the fact that there is unmet demand for nurses in health services around
      the world, some nurses migrate to destination countries to work as domestic
      workers. According to the literature, these nurses experience contradictions in
      class mobility and are at increased risk of exploitation and abuse. This article
      presents a critical discussion of the migration of nurses as domestic workers
      using the concept of 'global care chain'. Although several scholars have used the
      concept of global care chains to illustrate south to north migration of domestic
      workers and nurses, there is a paucity of literature on the migration of nurses
      to destination countries as domestic workers. The migration of nurses to
      destination countries as domestic workers involves the extraction of reproductive
      and skilled care labor without adequate compensatory mechanisms to such skilled
      nurses. Using the case of the Canadian Live-in Caregiver Program, the study
      illustrates how the global movement of internationally educated nurses as migrant
      domestic workers reinforces inequities that are structured along the power
      gradient of gender, class, race, nationality, and ethnicity, especially within an
      era of global nursing shortage. 

PMID- 23551294
TI  - A narrative literature review of older people's cancer pain experience.
AB  - AIMS AND OBJECTIVES: To synthesise current evidence about the experience of older
      people with cancer pain and consider how exploration of this may inform clinical
      practice and research. BACKGROUND: Cancer is more prevalent in older age.
      Evidence suggests that older people's pain is generally under-recognised and
      under treated. Pain is a significant concern for many people living and dying
      with cancer and may be of particular concern for older people who may have
      complex biopsychosocial needs. There is mounting evidence that older people and
      their families experience high level of unmet need generally and suboptimal pain
      in particular. DESIGN: Narrative literature review. METHOD: A comprehensive
      search of five electronic databases was undertaken between the years 1996-2010
      inclusive. Inclusion criteria were primary research papers relating older
      peoples' experiences of cancer pain, incorporating the verbal report or narrative
      account of experience of cancer. RESULTS: Seventeen papers met the criteria for
      inclusion in the review. Three major themes emerged from the literature: (1)
      emotional experience identified by older people with cancer pain, (2) effects of
      pain on life and living, and (3) how communication affects the experience or
      expression of cancer pain including subthemes of validating, trust and cultural
      effects on the communication of pain. CONCLUSION: There is limited research about
      older people's cancer pain from the perspective of the person experiencing the
      pain. This review highlights the need for further research into living and dying
      with cancer pain which incorporates the unique and individual experience of older
      people. RELEVANCE TO CLINICAL PRACTICE: Understanding the complexity and nature
      of older people's cancer pain experience should inform appropriate effective care
      that improves quality of life and promotes independence and dignity. Culturally
      sensitive training in communication may enhance understanding of the needs of
      older people with cancer pain.

PMID- 23551295
TI  - Immobilizing individual atoms beneath a corrugated single layer of boron nitride.
AB  - Single atoms, and in particular the least reactive noble gases, are difficult to
      immobilize at room temperature. Ion implantation into a crystal lattice has this
      capability, but the randomness of the involved processes does not permit much
      control over their distribution within the solid. Here we demonstrate that the
      boron nitride nanomesh, a corrugated single layer of hexagonal boron nitride (h
      BN) with a 3.2 nm honeycomb superstructure formed on a Rh(111) surface, can trap
      individual argon atoms at distinct subsurface sites at room temperature. A
      kinetic energy window for implantation is identified where the argon ions can
      penetrate the h-BN layer but not enter the Rh lattice. Scanning tunneling
      microscopy and photoemission data show the presence of argon atoms at two
      distinct sites within the nanomesh unit cell, confirmed also by density
      functional theory calculations. The single atom implants are stable in air.
      Annealing of implanted structures to 900 K induces the formation of highly
      regular holes of 2 nm diameter in the h-BN layer with adjacent flakes of the same
      size found on top of the layer. We explain this "can-opener" effect by the
      presence of a vacancy defect, generated during the penetration of the Ar ion
      through the h-BN lattice, and propagating along the rim of a nanomesh pore where
      the h-BN lattice is highly bent. The reported effects are also observed in
      graphene on ruthenium and for neon atoms.

PMID- 23551296
TI  - Penile lichen nitidus successfully treated with topical pimecrolimus 1% cream.

PMID- 23551297
TI  - Spontaneous formation of hydrophobic domains in isolated peptides.
AB  - Aromatic amino acids are known for their hydrophobicity and the active role they
      play in protein folding. Here, we investigate the intrinsic propensity of small
      peptides to form hydrophobic domains in the absence of solvent water molecules.
      The structures of three aromatic-rich isolated peptides, Ac-Phe-Phe-NH2 (FF), Ac
      Trp-Tyr-NH2 (WY), and Ac-Phe-Phe-Phe-NH2 (FFF), all in the gas phase, have been
      studied by infrared-ultraviolet (IR/UV) double resonance laser spectroscopy,
      aided by dispersion-corrected density functional theory (DFT-D) calculations.
      Spontaneous formation of hydrophobic domains is systematically observed, whatever
      the secondary structure adopted by the backbone. Various types of aromatic
      aromatic arrangements have been identified and associated to specific secondary
      structures, illustrating the interplay between the hydrophobic clusters and the
      backbone. Backbone NH amide groups surrounded by aromatic rings have also been
      evidenced and are found to contribute significantly to the stabilization of
      aromatic pairs. These results suggest that the formation of aromatic clusters
      involving contiguous residues might be a very efficient process leading to the
      formation of hydrophobic domains in the early stages of protein folding, well
      before a hydrophobic collapse into the tertiary structure.

PMID- 23551298
TI  - Angiographic findings after vaginal gauze packing: New insight into an old
      technique.
AB  - We had a transferred case of cervical ectopic pregnancy with hemorrhagic shock at
      6 weeks of gestation. Upon arrival at hospital, we performed tight and full
      vaginal gauze packing to push the uterus upward to control the patient's
      hemorrhage. Following stabilization of her general condition, she was treated
      with uterine artery embolization. Using angiography, the effectiveness of vaginal
      gauze packing for emergency hemostasis by the presumed mechanism of impairing
      blood flow through the uterine artery was demonstrated. To our knowledge, there
      are no reports that have previously demonstrated angiographic findings similar to
      ours after vaginal gauze packing. Vaginal gauze packing is an effective, rapid,
      and convenient hemostatic procedure able to be carried out in a time-sensitive
      and challenging situation. As a result, this procedure gives clinicians more time
      to improve the patients' general status and arrange for transfusion and further
      definitive treatment.

PMID- 23551299
TI  - A qualitative study exploring the psychosocial value of weekend camping
      experiences for children and adolescents with complex heart defects.
AB  - BACKGROUND: Children living with complex heart defects (CHD) are likely to have
      ongoing social, emotional, physical, and health concerns, and are in need of
      additional psychosocial support. Summer camps can provide therapeutic benefits.
      Little research exists regarding the value of shorter camping experiences from
      the perspectives of children with CHD. The aim of our study was to explore what
      children and adolescents with CHD considered meaningful when attending a
      therapeutic camping weekend in the company of peers with similar medical
      diagnoses. METHODS: Engaging a phenomenological approach we used participant
      generated photography and reflective semi-structured interviews to explore
      participants' lived experience and value derived from their weekend camping
      experiences. The study was completed with thirteen participants ranging in age
      from 9 to 16 years. Interviews were recorded and transcribed verbatim. Data were
      analysed using Van Manen's guidelines. RESULTS: Three themes reflecting the camp
      experiences were generated from the data. Meaningful experiences spanned three
      outcomes which had some overlapping influences: (i) Developing relationships and
      feeling accepted by peers and counsellors at camp; (ii) Enjoying and learning
      during the weekend; and (iii) Experiencing the natural and human-built
      therapeutic environmental features of camp. The camping programme features,
      inputs, and processes as identified by the participants in contributing to these
      outcomes are described. CONCLUSION: This qualitative study showed that children
      living with complex CHD valued the opportunity for participating in weekend
      camping experiences in the company of peers with similar heart defects. Findings
      contribute to a better understanding of what programme features and processes
      were considered meaningful. Given the scarcity of resources to devote to such
      social support activities, the findings may help professionals to plan effective
      interventions to maximize benefits during a shorter camping experience.

PMID- 23551300
TI  - Barley's lipid transfer protein: a new emerging allergen in pediatric
      anaphylaxis.

PMID- 23551301
TI  - Microevolution in time and space: SNP analysis of historical DNA reveals dynamic
      signatures of selection in Atlantic cod.
AB  - Little is known about how quickly natural populations adapt to changes in their
      environment and how temporal and spatial variation in selection pressures
      interact to shape patterns of genetic diversity. We here address these issues
      with a series of genome scans in four overfished populations of Atlantic cod
      (Gadus morhua) studied over an 80-year period. Screening of >1000 gene-associated
      single-nucleotide polymorphisms (SNPs) identified 77 loci that showed highly
      elevated levels of differentiation, likely as an effect of directional selection,
      in either time, space or both. Exploratory analysis suggested that temporal
      allele frequency shifts at certain loci may correlate with local temperature
      variation and with life history changes suggested to be fisheries induced.
      Interestingly, however, largely nonoverlapping sets of loci were temporal
      outliers in the different populations and outliers from the 1928 to 1960 period
      showed almost complete stability during later decades. The contrasting
      microevolutionary trajectories among populations resulted in sequential shifts in
      spatial outliers, with no locus maintaining elevated spatial differentiation
      throughout the study period. Simulations of migration coupled with observations
      of temporally stable spatial structure at neutral loci suggest that population
      replacement or gene flow alone could not explain all the observed allele
      frequency variation. Thus, the genetic changes are likely to at least partly be
      driven by highly dynamic temporally and spatially varying selection. These
      findings have important implications for our understanding of local adaptation
      and evolutionary potential in high gene flow organisms and underscore the need to
      carefully consider all dimensions of biocomplexity for evolutionarily sustainable
      management.

PMID- 23551302
TI  - AMPK involvement in endoplasmic reticulum stress and autophagy modulation after
      fatty liver graft preservation: a role for melatonin and trimetazidine cocktail.
AB  - Ischemia/reperfusion injury (IRI) associated with liver transplantation plays an
      important role in the induction of graft injury. Prolonged cold storage remains a
      risk factor for liver graft outcome, especially when steatosis is present.
      Steatotic livers exhibit exacerbated endoplasmic reticulum (ER) stress that
      occurs in response to cold IRI. In addition, a defective liver autophagy
      correlates well with liver damage. Here, we evaluated the combined effect of
      melatonin and trimetazidine as additives to IGL-1 solution in the modulation of
      ER stress and autophagy in steatotic liver grafts through activation of AMPK.
      Steatotic livers were preserved for 24 hr (4 degrees C) in UW or IGL-1 solutions
      with or without MEL + TMZ and subjected to 2-hr reperfusion (37 degrees C). We
      assessed hepatic injury (ALT and AST) and function (bile production). We
      evaluated ER stress (GRP78, PERK, and CHOP) and autophagy (beclin-1, ATG7, LC3B,
      and P62). Steatotic livers preserved in IGL-1 + MEL + TMZ showed lower injury and
      better function as compared to those preserved in IGL-1 alone. IGL-1 + MEL + TMZ
      induced a significant decrease in GRP78, pPERK, and CHOP activation after
      reperfusion. This was consistent with a major activation of autophagic parameters
      (beclin-1, ATG7, and LC3B) and AMPK phosphorylation. The inhibition of AMPK
      induced an increase in ER stress and a significant reduction in autophagy. These
      data confirm the close relationship between AMPK activation and ER stress and
      autophagy after cold IRI. The addition of melatonin and TMZ to IGL-1 solution
      improved steatotic liver graft preservation through AMPK activation, which
      reduces ER stress and increases autophagy. 

PMID- 23551304
TI  - Fucoxanthin ameliorates inflammation and oxidative reponses in microglia.
AB  - Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative
      disease that slowly destroys memory and thinking skills. In the brains of AD
      patients, signs of neuronal degeneration are accompanied by markers of microglial
      activation and inflammation as well as oxidant damage. This study tested the
      hypothesis that fucoxanthin, which is known to exert a variety of pharmacological
      properties, would ameliorate oxidative stress and inflammation in amyloid-beta42
      (Abeta42)-induced BV2 microglia cells. It was found that fucoxanthin treatment
      attenuated pro-inflammatory secretion in BV2 cells as determined by ELISA
      analysis. Suppressive effects of fucoxanthin on the phosphorylation mitogen
      activated protein kinase (MAPK) pathway were confirmed. Moreover, fucoxanthin was
      able to inhibit free radical-induced DNA oxidation in BV2 cells. This effect was
      associated with a significant reduction of intracellular reactive oxygen species
      (ROS) formation and recovery of antioxidative enzymes. The findings in this study
      suggest that fucoxanthin may serve as a negative feedback regulator of
      inflammation and oxidative stress in BV2 cells and thereby may protect neuronal
      cells from neurotoxic mediators released by microglia. 

PMID- 23551303
TI  - Measuring ward-based multidisciplinary healthcare team functioning: a validation
      study of the Team Functioning Assessment Tool (TFAT).
AB  - The team functioning assessment tool (TFAT) has been shown to be a reliable
      behavioral marker tool for assessing nontechnical skills that are critical to the
      success of ward-based healthcare teams. This paper aims to refine and shorten the
      length of the TFAT to improve usability, and establish its reliability and
      construct validity. Psychometric testing based on 110 multidisciplinary
      healthcare teams demonstrated that the TFAT is a reliable and valid tool for
      measuring team members' nontechnical skills in regards to Clinical Planning,
      Executive Tasks, and Team Functioning. Providing support for concurrent validity,
      high TFAT ratings were predicted by low levels of organizational constraints and
      high levels of group potency. There was also partial support for the negative
      relationships between time pressure, leadership ambiguity, and TFAT ratings. The
      paper provides a discussion on the applicability of the tool for assessing
      multidisciplinary healthcare team functioning in the context of improving team
      effectiveness and patient safety for ward-based hospital teams. 

PMID- 23551306
TI  - Collegiality and the sick doctor.

PMID- 23551305
TI  - Use of transnasal endoscopy for screening of esophageal squamous cell carcinoma
      in high-risk patients: yield rate, completion rate, and safety.
AB  - BACKGROUND: Patients with head and neck squamous cell carcinoma are at high risk
      for synchronous and/or metachronous esophageal cancer. The present study aimed to
      evaluate the feasibility and safety of unsedated transnasal endoscopy (TNE) for
      screening these high-risk patients. PATIENTS AND METHODS: Consecutive high-risk
      patients including patients with suspicious or diagnosed head and neck cancer or
      patients with alarming symptoms received screening TNE. All endoscopic
      procedures, including sequential conventional white-light, narrow-band imaging,
      and Lugol chromoendoscopy, were done without sedation. All suspicious lesions in
      the esophagus were biopsied for histological evaluation. The completion rate,
      procedure time, and significant adverse events of all endoscopic procedures were
      recorded and analyzed. RESULTS: From May 2007 to August 2011, a total of 500 TNE
      were carried out in 441 high-risk patients. Among them, 294 patients (66.7%) had
      diagnosed head and neck squamous cellcarcinoma, and most were hypopharyngeal
      cancer (n = 186). Esophageal squamous cell carcinomas and high-grade
      intraepithelial neoplasms were detected in 10.1% and 7.3%, respectively, of the
      cases. Completion rate of TNE in head and neck cancer was 96.7%; tumor
      obstruction and stenosis of anastomosis site were the main reasons for incomplete
      procedures. Mean duration of the endoscopic procedure was 14.6 min. One patient
      had post-endoscopic epistaxis while another patient had post-biopsy hemoptysis,
      both of whom were treated conservatively. No procedure-related mortality or
      significant morbidity occurred. CONCLUSION: Unsedated TNE is safe and feasible
      for screening synchronous or metachronous esophageal neoplasms in high-risk
      patients, especially those with head and neck cancer.

PMID- 23551307
TI  - Lipid profiles and persisting inflammation following critical illness in a
      central Australian population: a prospective longitudinal observational study.
AB  - No published data exist following the changes in lipid profile during and after
      an episode of acute illness for the Australian Indigenous population. This paper
      presents data focusing on lipid profiles and inflammatory markers in a group of
      survivors of critical illness in Central Australia, prospectively recruited to a
      larger trial exploring the medium-term sequelae of an intensive care unit
      admission. This data confirm that lipid profiles in acute illness are deranged,
      and that recovery may differ between indigenous and non-indigenous populations.

PMID- 23551308
TI  - Novel mutation in the TMEM127 gene associated with phaeochromocytoma.
AB  - Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours that arise
      from the adrenal glands or paraganglia (paragangliomas) within the abdomen,
      thorax and neck. Although it was originally suggested that approximately 10% of
      these tumours were inherited, it is now recognised that up to approximately 30%
      of these tumours are associated with a germline mutation in one of the
      phaeochromocytoma/paraganglioma susceptibility genes. Of the 12 currently known
      genes predisposing to these tumours, the TMEM127 gene is one of the more recently
      identified and appears to be present in approximately 2% of apparently sporadic
      phaeochromocytomas. We report a 33-year-old man who presented with an apparently
      sporadic adrenal phaeochromocytoma and was identified as carrying a novel TMEM127
      germline mutation, p.Gln139X. Patients harbouring a germline TMEM127 mutation
      most commonly present with an apparently sporadic solitary adrenal
      phaeochromocytoma. Testing patients who present with a phaeochromocytoma or
      paraganglioma for an underlying germline mutation needs to be considered in all
      patients due to implications for family members, but a strategy based on clinical
      and immunohistochemical findings would be prudent to limit costs.

PMID- 23551309
TI  - Immune-mediated cytopenias in human immunodeficiency virus: the first reported
      case of idiopathic aplastic anaemia successfully treated with immunosuppression.
AB  - Although isolated cytopenias are relatively common in human immunodeficiency
      virus (HIV), the incidence of aplastic anaemia is extremely rare. We report here
      the first case of a HIV-infected patient who developed severe idiopathic aplastic
      anaemia, and who was safely and effectively treated with anti-thymocyte globulin
      and cyclosporin. We briefly review immune-mediated cytopenias in HIV, including
      their frequency, pathophysiology and management strategies.

PMID- 23551310
TI  - Marijuana 'bong' smoking and tuberculosis.
AB  - The incidence of tuberculosis in the non-indigenous Australian population is low.
      However, in this paper we report on three cases of cavitating disease, which seem
      to be associated with a common illicit drug habit namely smoking marijuana using
      a makeshift pipe or bong. There was a total of 34 positive contacts of these
      cases and among the contacts sharing a bong with an index case was associated
      with a sixfold risk of transmission (odds ratio 6.5, confidence interval 1.4
      30.4, P = 0.016). When cavitating tuberculosis is detected in a young non
      indigenous native born Australian, marijuana use should be considered as a
      possible risk factor.

PMID- 23551311
TI  - Refractory long QT syndrome and the role of left cardiac sympathetic denervation.

PMID- 23551312
TI  - Systemic mastocytosis associated with severe osteoporosis in a male patient.

PMID- 23551313
TI  - Haemophagocytic lymphohistiocytosis and primary central nervous system lymphoma.

PMID- 23551314
TI  - Gouty arthritis in Australian Aborigines.

PMID- 23551315
TI  - Author reply to Douglas.

PMID- 23551316
TI  - Challenges in performing surveillance for central line associated bacteraemia in
      haematology-oncology units.

PMID- 23551317
TI  - Author reply to Worth and colleagues.

PMID- 23551318
TI  - Telerheumatology: not ready for prime time.

PMID- 23551319
TI  - Author reply to Rothschild.

PMID- 23551320
TI  - Mesiotemporal neuroimaging abnormalities in neurosyphilis and other causes of
      limbic encephalitis.

PMID- 23551321
TI  - Author reply to Kleinig.

PMID- 23551322
TI  - Rapid death after hospitalisation.

PMID- 23551323
TI  - JC -- a forgotten foe or a foe to be forgotten?

PMID- 23551324
TI  - Broadband ultraviolet A vs. psoralen ultraviolet A in the treatment of vitiligo:
      a randomized controlled trial.
AB  - BACKGROUND: Psoralen ultraviolet A (PUVA) and narrowband (NB)-UVB have been shown
      to be efficacious in the treatment of vitiligo. With large and repeated doses,
      UVA may lead to immediate skin darkening and to delayed tanning. Our previous
      experience with broadband (BB)-UVA in vitiligo showed encouraging results. AIM:
      To test the efficacy of BB-UVA in vitiligo and to evaluate if it could provide an
      alternative treatment for this condition. METHODS: This prospective, randomized,
      controlled, comparative clinical trial enrolled 45 patients with vitiligo, who
      were randomly divided into three groups, with group A receiving UVA 15 J/cm(2)
      /session, group B receiving UVA 10 J/cm(2) /session, and group C receiving PUVA.
      The patients received three sessions/week for 5 months, with 60 sessions in
      total. RESULTS: At the mid-point of treatment, clinical response was
      significantly higher in patients receiving PUVA than in the other two groups At
      the end of the study, clinical response was comparable for groups A and C (UVA 15
      J/cm(2) and PUVA, respectively), and both were significantly higher than the
      group receiving UVA 10 J/cm(2) . Patients in the PUVA group responded mainly with
      perifollicular pigmentation, whereas those receiving UVA responded mainly with
      lesional tanning. CONCLUSIONS: BB-UVA at a dose of 15 J/cm(2) /session gives
      results for vitiligo that are comparable to PUVA, suggesting it might be useful
      when oral psoralens are contraindicated.

PMID- 23551325
TI  - Nursing and health-care assistant experience of supervision in a medium secure
      psychiatric service for women: implications for service development.
AB  - In secure psychiatric services where the potential for 'burnout' by nurses is
      high, clinical supervision is viewed as a key to reflective practice to support
      staff in stressful working environments. Barriers to the uptake of clinical
      supervision in such service settings are personal and organizational. The study
      was prompted by the need to evaluate the effectiveness of supervision for
      registered nurses and health-care assistants (HCAs) and a desire to use survey
      findings to improve the quality and uptake of supervision. The study examined the
      perceived benefits, the best practice elements and the practical aspects of
      clinical supervision including how to improve practice. An approximate uptake of
      clinical supervision by 50% of staff confirmed previous findings; that HCAs were
      significantly less likely to engage in supervision and less likely to perceive
      benefit from it. Initiatives to address the training and managerial obstacles to
      the provision of formal supervision are described.

PMID- 23551326
TI  - Expression and localization of vascular endothelial growth factor and its
      receptors in the corpus luteum during oestrous cycle in water buffaloes (Bubalus
      bubalis).
AB  - The aim of this study was to document the expression and localization of VEGF
      system comprising of VEGF isoforms (VEGF 120, VEGF 164 and VEGF 188) and their
      receptors (VEGFR1 and VEGFR2) in buffalo corpus luteum (CL) obtained from
      different stages of the oestrous cycle. Real-time RT-PCR (qPCR), Western blot and
      immunohistochemistry were applied to investigate mRNA expression, protein
      expression and localization of examined factors. In general, all the components
      of VEGF system (the VEGF isoforms and their receptors) were found in the water
      buffalo CL during the oestrous cycle. The mRNA as well as protein expression of
      VEGF system was highest during the early and mid-luteal phase, which later
      steadily decreased (p < 0.05) after day 10 to reach the lowest level in regressed
      CL. As demonstrated by immunohistochemistry, VEGF protein was localized
      predominantly in luteal cells; however, VEGFR1 and VEGFR2 were localized in
      luteal cells as well as in endothelial cells. In conclusion, the dynamics of
      expression and localization of VEGF system in buffalo corpora lutea during the
      luteal phase were demonstrated in this study, indicating the possible role of
      VEGF system in the regulation of luteal angiogenesis and proliferation of luteal
      as well as endothelial cells through their non-angiogenic function. 

PMID- 23551327
TI  - C-H arylation of benzoquinone in water through aniline activation: synergistic
      effect of graphite-supported copper oxide nanoparticles.
AB  - A homemade CuONPs/Gr catalyst was found to be efficient for the C-H arylation of
      benzoquinone. This methodology represents the first example of a Meerwein
      arylation catalyzed by a heterogeneous catalyst.

PMID- 23551328
TI  - Challenges to the global control of tuberculosis.
AB  - Diagnosis and treatment of tuberculosis (TB) will likely navigate a historical
      turning point in the 2010s with a new management paradigm emerging. However,
      global control of TB remains a formidable challenge for the decades to come. The
      estimated case detection rate of TB globally was 66%, and there were 310 000
      estimated multidrug-resistant TB (MDR-TB) cases among the 6.2 million TB patients
      notified in 2011. Although new tools are being introduced for the diagnosis of
      MDR-TB, there are operational and cost issues related to their use that require
      urgent attention, so that the poor and vulnerable can benefit. World Health
      Organization (WHO) estimated that globally, 3.7% of new cases and 20% of
      previously treated cases have MDR-TB. However, the scale-up of programmatic
      management of drug-resistant TB is slow, with only 60 000 MDR-TB cases notified
      to WHO in 2011. The overall proportion of treatment success of MDR-TB notified
      globally in 2009 was 48%, far below the global target of 75% success rate.
      Although new tools and drugs have the potential to significantly improve both
      case detection and treatment outcome, adequate health systems and human resources
      are needed for rapid uptake and proper implementation to have the impact required
      to eliminate TB. Hence, the global TB community should broaden its scope, seek
      intersectoral collaboration and advocate for cost reduction of new tools, while
      ensuring that the basics of TB control are implemented to reduce the TB burden
      through the current 'prevention through case management' paradigm.

PMID- 23551329
TI  - Low-dose dexamethasone treatment promotes the pro-survival signalling pathway in
      the adult rat prefrontal cortex.
AB  - Synthetic glucocorticoid dexamethasone (DEX), a highly potent anti-inflammatory
      and immunosuppressive agent, is widely used in the treatment of brain cancer, as
      well as for inflammatory and autoimmune diseases. The present study aimed to
      determine whether low-dose subchronic DEX treatment (100 MUg/kg for eight
      consecutive days) exerts long-term effects on apoptosis in the adult rat
      prefrontal cortex (PFC) by examining the expression of cell death-promoting
      molecules [poly(ADP-ribose) polymerase (PARP), p53, procaspase 3, cleaved caspase
      3, Bax] and cell-survival molecules (AKT, Bcl-2). The results obtained revealed
      that body, thymus and adrenal gland weights, as well corticosterone levels, in
      the serum and PFC were reduced 1 day after the last DEX injection. In the PFC,
      DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and an
      enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to the
      mitochondria. An unaltered profile with respect to the protein expression of
      apoptotic molecules PARP, procaspase 3 and Bax was detected, whereas p53 protein
      was decreased. Reverse transcriptase -polymerase chain reaction analysis showed a
      decrease of p53 mRNA levels and no significant difference in Bcl-2 and Bax mRNA
      expression in DEX-treated rats. Finally, a DNA fragmentation assay and Fluoro
      Jade staining demonstrated no considerable changes in apoptosis in the rat PFC.
      Our findings support the concept that low-dose DEX creates a hypocorticoid state
      in the brain and also indicate that subchronic DEX treatment activates the pro
      survival signalling pathway but does not change apoptotic markers in the rat PFC.
      This mechanism might be relevant for the DEX-induced apoptosis resistance
      observed during and after chemotherapy of patients with brain tumours.

PMID- 23551330
TI  - Evaluation and management of hepatic injury induced by oxaliplatin-based
      chemotherapy in patients with hepatic resection for colorectal liver metastasis.
AB  - Patients with colorectal liver metastasis (CRLM) can be cured with surgical
      resection. Recent advances in systemic chemotherapy, including molecular target
      agents, can be used to introduce "conversion surgery" and achieve R0 resection
      even in patients with initially unresectable CRLM. Furthermore, neoadjuvant
      chemotherapy also tries to be applied in patients with resectable CRLM to
      maximize the remnant liver and reduce the residual micrometastasis before
      surgery. The development of chemotherapy-induced hepatic injuries is increasingly
      being recognized, including sinusoidal obstructive syndrome (SOS), steatosis,
      steatohepatitis and biliary sclerosis. Especially, oxaliplatin (L-OHP)-based
      chemotherapy in clinical settings appears to be primarily associated with SOS.
      Various reports have tried to demonstrate the rationale of the correlation
      between L-OHP-based chemotherapy and SOS for the following hepatic surgery. While
      we can recognize that this pathophysiological disadvantage leads to hepatic
      dysfunction and the increasing postoperative morbidity, the essential part of
      this problem including clinical disadvantage, onset mechanism, evaluation
      systems, and targeted agents for prevention and treatment of SOS continue to be
      unclear. In this review, we summarize the current experience with hepatic injury
      induced by L-OHP-based chemotherapy, focusing on SOS-based on clinical and
      experimental data, in order to assist in the resolution of these identified
      factors. Finally, the need for reliable methods to identify the risk of SOS, to
      evaluate SOS status and to predict the safety of surgical treatment in patients
      with chemotherapy prior to surgery will be emphasized. 

PMID- 23551331
TI  - Catastrophic manifestations of air embolism in a patient with atrioesophageal
      fistula following minimally invasive surgical ablation of atrial fibrillation.

PMID- 23551332
TI  - Hypogammaglobulinemia in the early period after liver transplantation in
      children.
AB  - Data, on the kinetic and serum levels of immunoglobulins in the immediate post
      liver transplantation (LTx) period, are sparse with existing studies limited to
      adults or case reports of children. The aim of this study is to describe the
      phenomenon of hypogammaglobulinemia (HGG) in the immediate post-transplantation
      period among children undergoing LTx. A retrospective 10-yr chart review was
      conducted of all children who underwent LTx at a fourth-level pediatric medical
      center. Fifty-seven, of the 76 children who underwent LTx, were included in the
      study. Seventeen (29.8%) (mean age, 6.8 +/- 5.2 yr) had HGG (11-IgG, 1-IgG+IgA, 1
      IgG+IgM, 4-IgG+IgA+IgM), detected at 2 to 25 d after transplantation. Abdominal
      fluid was drained for 5 to 42 d; the amount drained until detection of HGG
      measured 27-668 mL/kg. HGG was associated with increased infection rate 0.9
      episodes/patient vs. 0.17 episodes/patient (p < 0.01) in children without
      detected HGG. In conclusion, HGG is not rare in the immediate post-LTx period in
      children, and it may place patients at increased risk of infection. Further
      studies are needed to delineate the rate of occurrence, risk factors, and
      clinical implications of hypogammaglobulinemia in this patient population.

PMID- 23551333
TI  - The evolutionary history of Xiphophorus fish and their sexually selected sword: a
      genome-wide approach using restriction site-associated DNA sequencing.
AB  - Next-generation sequencing (NGS) techniques are now key tools in the detection of
      population genomic and gene expression differences in a large array of organisms.
      However, so far few studies have utilized such data for phylogenetic estimations.
      Here, we use NGS data obtained from genome-wide restriction site-associated DNA
      (RAD) (~66000 SNPs) to estimate the phylogenetic relationships among all 26
      species of swordtail and platyfish (genus Xiphophorus) from Central America. Past
      studies, both sequence and morphology-based, have differed in their inferences of
      the evolutionary relationships within this genus, particularly at the species
      level and among monophyletic groupings. We show that using a large number of
      markers throughout the genome, we are able to infer the phylogenetic
      relationships with unparalleled resolution for this genus. The relationships
      among all three major clades and species within each of them are highly resolved
      and consistent under maximum likelihood, Bayesian inference and maximum
      parsimony. However, we also highlight the current cautions with this data type
      and analyses. This genus exhibits a particularly interesting evolutionary history
      where at least two species may have arisen through hybridization events. Here, we
      are able to infer the paternal lineages of these putative hybrid species. Using
      the RAD-marker-based tree we reconstruct the evolutionary history of the sexually
      selected sword trait and show that it may have been present in the common
      ancestor of the genus. Together our results highlight the outstanding capacity
      that RAD sequencing data has for resolving previously problematic phylogenetic
      relationships, particularly among relatively closely related species.

PMID- 23551334
TI  - Catastrophic medical malpractice payouts in the United States.
AB  - Catastrophic medical malpractice payouts, $1 million or greater, greatly
      influence physicians' practice, hospital policy, and discussions of healthcare
      reform. However, little is known about the specific characteristics and overall
      cost burden of these payouts. We reviewed all paid malpractice claims nationwide
      using the National Practitioner Data Bank over a 7-year period (2004-2010) and
      used multivariate regression to identify risk factors for catastrophic and
      increased overall payouts. Claims with catastrophic payouts represented 7.9%
      (6,130/77,621) of all paid claims. Factors most associated with catastrophic
      payouts were patient age less than 1 year; quadriplegia, brain damage, or
      lifelong care; and anesthesia allegation group. Compared with court judgments,
      settlement was associated with decreased odds of a catastrophic payout (odds
      ratio, 0.31; 95% confidence interval [CI], 0.22-0.42) and lower estimated average
      payouts ($124,863; 95% CI, $101,509-144,992). A physician's years in practice and
      previous paid claims history had no effect on the odds of a catastrophic payout.
      Catastrophic payouts averaged $1.4 billion per year or 0.05% of the National
      Health Expenditures. Preventing catastrophic malpractice payouts should be only
      one aspect of comprehensive patient safety and quality improvement strategies.
      Future studies should evaluate the benefits of targeted interventions based on
      specific patient safety event characteristics.

PMID- 23551335
TI  - Molecular mechanism of polyacrylate helix sense switching across its free energy
      landscape.
AB  - Helical polymers with switchable screw sense are versatile frameworks for chiral
      functional materials. In this work, we reconstructed the free energy landscape of
      helical poly(2,7-bis(4-tert-butylphenyl)fluoren-9-yl acrylate) [poly(BBPFA)], as
      its racemization is selectively driven by light without any rearrangement of
      chemical bonds. The chirality inversion was enforced by atomistic free energy
      simulations using chirality indices as reaction coordinates. The free energy
      landscape reproduced the experimental electronic circular dichroism spectra. We
      propose that the chirality inversion of poly(BBPFA) proceeds from a left-handed
      31 helix via multistate free energy pathways to reach the right-handed 31 helix.
      The inversion is triggered by the rotation of biphenyl units with an activation
      barrier of 38 kcal/mol. To the best of our knowledge, this is the first report on
      the chiral inversion mechanism of a helical polymer determined in a quantitative
      way in the framework of atomistic free energy simulations.

PMID- 23551336
TI  - Flooding, resettlement, and change in livelihoods: evidence from rural
      Mozambique.
AB  - Post-disaster development policies, such as resettlement, can have major impacts
      on communities. This paper examines how and why people's livelihoods change as a
      result of resettlement, and relocated people's views of such changes, in the
      context of natural disasters. It presents two historically-grounded, comparative
      case studies of post-flood resettlement in rural Mozambique. The studies
      demonstrate a movement away from rain-fed subsistence agriculture towards
      commercial agriculture and non-agricultural activities. The ability to secure a
      viable livelihood was a key determinant of whether resettlers remained in their
      new locations or returned to the river valleys despite the risks posed by floods.
      The findings suggest that more research is required to understand i) why
      resettlers choose to stay in or abandon designated resettlement areas, ii) what
      is meant by 'voluntary' and 'involuntary' resettlement in the realm of post
      disaster reconstruction, and iii) the policy drivers of resettlement in
      developing countries.

PMID- 23551337
TI  - Radiographic characterization of presumed plate-like atelectasis in 75
      nonanesthetized dogs and 15 cats.
AB  - Discrete discoid or linear areas of increased soft opacity have been observed
      within the pulmonary parenchyma in thoracic radiographs of dogs and cats. Similar
      radiographic findings have been described in humans and termed plate-like
      atelectasis. The purpose of this retrospective study was to describe locations
      and characteristics of presumed plate-like atelectasis, presence of concurrent
      thoracic disease(s), and presence of persistent pulmonary changes on recheck
      thoracic radiographic studies in a cohort of dogs and cats. Hospital records
      between 2004 and 2011 were searched and a total of 90 cases were included (75
      dogs and 15 cats, 2-17 years of age). Plate-like atelectasis was most commonly
      found in left lateral radiographs. Plate-like atelectasis was observed in the
      cranial thorax and was oriented in a dorsocranial to ventrocaudal direction in 68
      (75%) patients. Plate-like atelectasis averaged 29.6 +/- 14.4 mm in length and
      2.6 +/- 1.3 mm in width. In 57 of the 90 patients (63%), plate-like atelectasis
      was the only abnormality found. Plate-like atelectasis was present in 7 of 22
      cases where follow-up radiographs were available. Findings from the current study
      indicated that, while the etiology of plate-like atelectasis remains unknown,
      anatomic variations in sublobar pulmonary anatomy might account for pleural areas
      of atelectasis. The authors propose that the presence of plate-like atelectasis
      may represent areas of atelectasis that track along sublobar lung lobe
      separations, an area of hypoventilation or decreased collateral ventilation,
      and/or area of decreased localized surfactant deficiency. 

PMID- 23551338
TI  - RNA interference suppression of lignin biosynthesis increases fermentable sugar
      yields for biofuel production from field-grown sugarcane.
AB  - The agronomic performance, cell wall characteristics and enzymatic
      saccharification efficiency of transgenic sugarcane plants with modified lignin
      were evaluated under replicated field conditions. Caffeic acid O
      methyltransferase (COMT) was stably suppressed by RNAi in the field, resulting in
      transcript reduction of 80%-91%. Along with COMT suppression, total lignin
      content was reduced by 6%-12% in different transgenic lines. Suppression of COMT
      also altered lignin composition by reducing syringyl units and p-coumarate
      incorporation into lignin. Reduction in total lignin by 6% improved
      saccharification efficiency by 19%-23% with no significant difference in biomass
      yield, plant height, stalk diameter, tiller number, total structural
      carbohydrates or brix value when compared with nontransgenic tissue culture
      derived or transgenic control plants. Lignin reduction of 8%-12% compromised
      biomass yield, but increased saccharification efficiency by 28%-32% compared with
      control plants. Biomass from transgenic sugarcane lines that have 6%-12% less
      lignin requires approximately one-third of the hydrolysis time or 3- to 4-fold
      less enzyme to release an equal or greater amount of fermentable sugar than
      nontransgenic plants. Reducing the recalcitrance of lignocellulosic biomass to
      saccharification by modifying lignin biosynthesis is expected to greatly benefit
      the economic competitiveness of sugarcane as a biofuel feedstock. 

PMID- 23551339
TI  - Chewing gum reduces postoperative ileus following abdominal surgery: a meta
      analysis of 17 randomized controlled trials.
AB  - BACKGROUND AND AIM: Chewing gum proposal has been used in surgery to reduce
      postoperative ileus for more than 10 years; however, the efficacy remains
      imprecise. The aim of this study was to accurately assess whether the use of the
      chewing gum could reduce duration of postoperative ileus following the abdominal
      surgery. METHODS: A systematic review was conducted in Medline, EMBASE, and the
      Cochrane Library through December 2012 to identify randomized controlled trials
      comparing with and without the use of chewing gum in patients undergoing
      abdominal surgery. The outcome of interest was time to flatus, time to bowel
      movement, and length of stay. Subgroup analyses were performed to examine the
      impact of different studies structural design. Cumulative meta-analyses were used
      to examine how the evidence has changed over time. RESULTS: Seventeen randomized
      controlled trials involving 1374 participants were included. Overall time (in
      days) for the patients to pass flatus (weighted mean difference [WMD], -0.31; 95%
      confidence interval [CI], -0.43 to -0.19; P = 0.000); time to bowel movement
      (WMD, -0.51; 95% CI, -0.73 to -0.29; P = 0.000); and length of stay (WMD, -0.72;
      95% CI, -1.02 to -0.43; P = 0.000) were significantly reduced in the treatment
      group. However, both of these results demonstrated significant heterogeneity. No
      evidence of publication bias was observed. Cumulative meta-analysis showed that
      chewing gum reduces duration of postoperative ileus that has been available for
      over 6 years. CONCLUSIONS: Results of the meta-analysis suggest that chewing gum
      following abdominal surgery offers benefits in reducing the time of postoperative
      ileus.

PMID- 23551340
TI  - Visualizing metabolite distribution and enzymatic conversion in plant tissues by
      desorption electrospray ionization mass spectrometry imaging.
AB  - In comparison with the technology platforms developed to localize transcripts and
      proteins, imaging tools for visualization of metabolite distributions in plant
      tissues are less well developed and lack versatility. This hampers our
      understanding of plant metabolism and dynamics. In this study, we demonstrate
      that desorption electrospray ionization mass spectrometry imaging (DESI-MSI) of
      tissue imprints on porous Teflon may be used to accurately image the distribution
      of even labile plant metabolites such as hydroxynitrile glucosides, which
      normally undergo enzymatic hydrolysis by specific beta-glucosidases upon cell
      disruption. This fast and simple sample preparation resulted in no substantial
      differences in the distribution and ratios of all hydroxynitrile glucosides
      between leaves from wild-type Lotus japonicus and a beta-glucosidase mutant plant
      that lacks the ability to hydrolyze certain hydroxynitrile glucosides. In wild
      type, the enzymatic conversion of hydroxynitrile glucosides and the concomitant
      release of glucose were easily visualized when a restricted area of the leaf
      tissue was damaged prior to sample preparation. The gene encoding the first
      enzyme in hydroxynitrile glucoside biosynthesis in L. japonicus leaves, CYP79D3,
      was found to be highly expressed during the early stages of leaf development, and
      the hydroxynitrile glucoside distribution in mature leaves reflected this early
      expression pattern. The utility of direct DESI-MSI of plant tissue was
      demonstrated using cryo-sections of cassava (Manihot esculenta) tubers. The
      hydroxynitrile glucoside levels were highest in the outer cell layers, as
      verified by LC-MS analyses. The unexpected discovery of a hydroxynitrile-derived
      di-glycoside shows the potential of DESI-MSI to discover and guide investigations
      into new metabolic routes.

PMID- 23551341
TI  - Coarse particulate matter and airborne endotoxin within wood stove homes.
AB  - Emissions from indoor biomass burning are a major public health concern in
      developing areas of the world. Less is known about indoor air quality,
      particularly airborne endotoxin, in homes burning biomass fuel in residential
      wood stoves in higher income countries. A filter-based sampler was used to
      evaluate wintertime indoor coarse particulate matter (PM10-2.5) and airborne
      endotoxin (EU/m3, EU/mg) concentrations in 50 homes using wood stoves as their
      primary source of heat in western Montana. We investigated number of residents,
      number of pets, dampness (humidity), and frequency of wood stove usage as
      potential predictors of indoor airborne endotoxin concentrations. Two 48-h
      sampling events per home revealed a mean winter PM10-2.5 concentration (+/- s.d.)
      of 12.9 (+/- 8.6) MUg/m3, while PM2.5 concentrations averaged 32.3 (+/- 32.6)
      MUg/m3. Endotoxin concentrations measured from PM10-2.5 filter samples were 9.2
      (+/- 12.4) EU/m3 and 1010 (+/- 1524) EU/mg. PM10-2.5 and PM2.5 were significantly
      correlated in wood stove homes (r = 0.36, P < 0.05). The presence of pets in the
      homes was associated with PM10-2.5 but not with endotoxin concentrations.
      Importantly, none of the other measured home characteristics was a strong
      predictor of airborne endotoxin, including frequency of residential wood stove
      usage.

PMID- 23551342
TI  - Melatonin antagonizes hypoxia-mediated glioblastoma cell migration and invasion
      via inhibition of HIF-1alpha.
AB  - Hypoxia is a crucial factor in tumor aggressiveness and resistance to therapy,
      especially in glioblastoma. Our previous results have shown that melatonin exerts
      antimigratory and anti-invasive action in glioblastoma cells under normoxia.
      However, the effect of melatonin on migration and invasion of glioblastoma cells
      under hypoxic condition remains poorly understood. Here, we show that melatonin
      strongly reduced hypoxia-mediated invasion and migration of U251 and U87
      glioblastoma cells. In addition, we found that melatonin significantly blocked
      HIF-1alpha protein expression and suppressed the expression of downstream target
      genes, matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor
      (VEGF). Furthermore, melatonin destabilized hypoxia-induced HIF-1alpha protein
      via its antioxidant activity against ROS produced by glioblastoma cells in
      response to hypoxia. Along with this, HIF-1alpha silencing by small interfering
      RNA markedly inhibited glioblastoma cell migration and invasion, and this
      appeared to be associated with MMP-2 and VEGF under hypoxia. Taken together, our
      findings suggest that melatonin suppresses hypoxia-induced glioblastoma cell
      migration and invasion via inhibition of HIF-1alpha. Considering the fact that
      overexpression of the HIF-1alpha protein is often detected in glioblastoma
      multiforme, melatonin may prove to be a potent therapeutic agent for this tumor. 

PMID- 23551344
TI  - Polysaccharide hemostatic system for hemostasis management in colorectal
      endoscopic mucosal resection.
AB  - BACKGROUND: A new polysaccharide hemostatic system (EndoClot(TM) ) was recently
      developed for bleeding control in gastrointestinal tract endoscopy; however, its
      efficacy and safety is not yet well established in colorectal endoscopic mucosal
      resection (EMR). The aim of the present study was to observe the bleeding control
      effect after EMR in the colorectum. PATIENTS AND METHODS: EndoClot(TM) was
      applied immediately to mucosal defects after resection whether or not there was
      post-resection bleeding. Bleeding was monitored post-procedurally by clinical
      findings including positive stool occult blood test and by second-look endoscopy.
      Hemostasis, rebleeding rates and treatment-related complications were observed.
      RESULTS: In total, 82 patients were enrolled, totaling 181 lesions. Among them,
      20 lesions in 18 cases showed bleeding immediately after the procedure. Among
      them, two lesions were treated by combined hot biopsy forceps, and complete
      hemostasis was achieved in all cases without surgery. It took 1.1 min (0.4-2.1)
      tocarry out hemostasis treatment. Rebleeding with positive stool test and
      colonoscopy recurred in three of 18 patients with immediate post-procedural
      bleeding. In patients without immediate post-procedural bleeding, three patients
      were confirmed with delayed bleeding. No major adverse events of treatment or
      procedure-related serious adverse events were reported during a 30-day follow up.
      Colonoscopy was done in selected patients at 30 days and full recovery of mucosal
      defect was achieved in all cases. CONCLUSION: Polysaccharide hemostatic system
      effectively achieves hemostasis in controlling and preventing EMR-related
      bleeding with the advantage of simple application; thus it might be a useful
      alternative in treating bleeding endoscopically.

PMID- 23551345
TI  - Predictors of good-quality counselling from the perspective of hospitalised
      chronically ill adults.
AB  - AIMS AND OBJECTIVES: To determine the factors that predict the quality of patient
      counselling from the perspective of hospitalised chronically ill adults.
      BACKGROUND: In view of the growing number of adults with chronic diseases and a
      lack of resources in health care, it would be valuable for healthcare
      professionals to know which factors result in good-quality counselling for such
      individuals. DESIGN: The study used a cross-sectional, descriptive design.
      METHODS: Data were collected from chronically ill adults (n = 106) in northern
      Finland and were analysed using logistic regression. RESULTS: Counselling
      implementation was perceived to be of good quality if it was preplanned (odds
      ratio = 24.07) and patient-centred (odds ratio = 16.03) and if interaction during
      counselling (odds ratio = 13.27) was good. Counselling about social support (odds
      ratio = 14.78), preplanned counselling (odds ratio = 9.69), counselling about the
      results of investigations (odds ratio = 7.84) and counselling about disease
      progression (odds ratio = 7.66) were statistically significant predictors of the
      content being considered good quality. The effects of counselling on disease
      treatment (odds ratio = 11.33), patient-centred counselling (odds ratio = 9.75)
      and counselling about the effects of attitudes (odds ratio = 9.52) were
      statistically significant predictors of highly beneficial counselling.
      Counselling about the effects of disease treatment (odds ratio = 9.71) and
      interaction during counselling (odds ratio = 4.91) predicted the quality of
      counselling materials and methods. CONCLUSION: The results could be used to help
      healthcare professionals to ensure good-quality counselling by highlighting the
      areas that are most important to meet the expectations of chronically ill adults.
      RELEVANCE TO CLINICAL PRACTICE: The results can be used to develop the quality of
      chronically ill adults' counselling as well as to educate staff to focus better
      on chronically ill patients' counselling because it is necessary to develop new
      ways to offer more patient-centred counselling in order to address patients'
      needs and fit care to patients' lifestyles.

PMID- 23551346
TI  - Transcriptome-wide analysis of vernalization reveals conserved and species
      specific mechanisms in Brachypodium.
AB  - Several temperate cereals need vernalization to promote flowering. Little,
      however, is known about the vernalization-memory-related genes, and almost no
      comparative analysis has been performed. Here, RNA-Seq was used for transcriptome
      analysis in non-vernalized, vernalized and post-vernalized Brachypodium
      distachyon (L.) Beauv. seedlings. In total, the expression of 1,665 genes showed
      significant changes (fold change >=4) in response to vernalization. Among them,
      674 putative vernalization-memory-related genes with a constant response to
      vernalization were significantly enriched in transcriptional regulation and
      monooxygenase-mediated biological processes. Comparative analysis of
      vernalization-memory-related genes with barley demonstrated that the oxidative
      stress response was the most conserved pathway between these two plant species.
      Moreover, Brachypodium preferred to regulate transcription and protein
      phosphorylation processes, while vernalization-memory-related genes, whose
      products are cytoplasmic membrane-bound-vesicle-located proteins, were preferred
      to be regulated in barley. Correlation analysis of the vernalization-related
      genes with barley revealed that the vernalization mechanism was conserved between
      these two plant species. In summary, vernalization, including its memory
      mechanism, is conserved between Brachypodium and barley, although several species
      specific features also exist. The data reported here will provide primary
      resources for subsequent functional research in vernalization. 

PMID- 23551347
TI  - 'We have got the tools': Qualitative evaluation of a mental health Wellness
      Recovery Action Planning (WRAP) education programme in Ireland.
AB  - In recent years, there has been a consistent drive to incorporate Recovery
      principles into the Irish mental health services. A group of Irish mental health
      service providers came together and delivered a 5-day Wellness Recovery Action
      Planning (WRAP) facilitator's programme. The programme was developed and
      delivered by key stakeholders including people with self-experience of mental
      health problem. This paper presents the qualitative findings from an evaluation
      of these facilitator's programmes. Three focus groups were held with 22 people,
      the majority of who described themselves as mental health professionals and/or
      people with self-experience of mental health problems. Data were analysed using a
      thematic approach and yielded four themes. Although the participants were
      positive about the programme and felt that their knowledge of Recovery and WRAP
      had improved, they felt that they still lacked confidence in terms of the
      presentation skills required for facilitating Recovery and WRAP programmes. The
      findings suggest that mental health service providers who wish to develop service
      users and clinicians as WRAP facilitators need to put more emphasis on the
      provision of facilitation and presentation skills in the programmes they develop.

PMID- 23551348
TI  - Listeria monocytogenes pleuritis: report of a geriatric case.

PMID- 23551349
TI  - Pilot study of pharmacological treatment for frontotemporal dementia: risk of
      donepezil treatment for behavioral and psychological symptoms.

PMID- 23551350
TI  - Successful treatment of severe bronchiectasis in the elderly using
      trimethoprim/sulfamethoxazole.

PMID- 23551351
TI  - Case report: Beneficial effect of 11beta-hydroxylase inhibitor in the management
      of an elderly patient with an androgen-producing inoperable adrenal tumor.

PMID- 23551352
TI  - Does magnesium level play a role in the association between major depression and
      cortisol?

PMID- 23551353
TI  - Association between head injury and Parkinson's disease: an observation in
      Taiwan.

PMID- 23551354
TI  - Rivastigmine patch and massage for Alzheimer's disease patients.

PMID- 23551355
TI  - Pilot study of pharmacological treatment for frontotemporal lobar degeneration:
      effect of lavender aroma therapy on behavioral and psychological symptoms.

PMID- 23551356
TI  - N-terminal domain of Pyrococcus furiosus l-asparaginase functions as a non
      specific, stable, molecular chaperone.
AB  - The enzyme l-asparaginase of Pyrococcus furiosus (PfA) functions as a dimer with
      each monomer consisting of distinct N- and C-terminal domains (NPfA and CPfA,
      respectively), connected by a linker. Here we present data to show that NPfA
      functions as a non-specific molecular chaperone. Independently expressed NPfA
      refolded spontaneously whereas CPfA formed insoluble aggregates. However, when
      mixed and refolded together, NPfA augmented CPfA to fold with ~90% recovery. NPfA
      also protected a variety of substrate proteins from thermal and refolding
      mediated aggregation as monitored by a reduction in light scattering. The co
      appearance of substrate protein with NPfA in antibody pull-down assays as well as
      in eluted gel filtration peaks indicated direct protein-protein interaction.
      These interactions were hydrophobic in nature as determined by 8-anilino-1
      naphthalene sulfonic acid fluorescence. NPfA inhibited polyglutamine-mediated
      amyloid formation and also facilitated disintegration of preformed amyloid
      fibrils of amyloid-beta (1-42) as determined by reverse-phase HPLC-based
      sedimentation assay and thioflavin T binding assays, respectively. Dynamic light
      scattering experiments suggested that NPfA readily assembled into polydispersed
      oligomeric species. With no sequence similarity to alpha-crystallin or any known
      molecular chaperone, we present here NPfA as a novel molecular chaperone.

PMID- 23551357
TI  - Prevalence of placenta praevia by world region: a systematic review and meta
      analysis.
AB  - OBJECTIVES: (i) To estimate the prevalence burden of placenta praevia in each
      world region, and (ii) to investigate potential sources of heterogeneity.
      METHODS: Systematic review of the literature and random-effects meta-analysis.
      Potential sources of heterogeneity were investigated using meta-regression.
      RESULTS: The overall prevalence of placenta praevia was 5.2 per 1000 pregnancies
      (95% CI: 4.5-5.9). However, there was evidence of regional variation (P =
      0.0001); prevalence was highest among Asian studies (12.2 per 1000 pregnancies;
      95% CI: 9.5-15.2) and lower among studies from Europe (3.6 per 1000 pregnancies;
      95% CI: 2.8-4.6), North America (2.9 per 1000 pregnancies; 95% CI: 2.3-3.5) and
      Sub-Saharan Africa (2.7 per 1000 pregnancies; 95% CI: 0.3-11.0). The prevalence
      of major placenta praevia was 4.3 per 1000 pregnancies (95% CI: 3.3-5.4).
      CONCLUSION: The prevalence of placenta praevia is low at around 5 per 1000
      pregnancies. There is some evidence suggestive of regional variation in its
      prevalence, but it is not possible to determine from existing data whether this
      is due to true ethnic differences or other unknown factor(s).

PMID- 23551358
TI  - Evaluation of diagnostic value of four tumor markers in bronchoalveolar lavage
      fluid of peripheral lung cancer.
AB  - AIM: The diagnostic role of carcinoembryonic antigen (CEA), squamous cell
      carcinoma (SCC) antigen, Cyfra 21-1 and neuron-specific enolase (NSE) in the
      bronchoalveolar lavage fluid (BALF) for lung cancer is still controversial. The
      aim of this study was to evaluate the diagnostic value of these four tumor
      markers in BALF for peripheral lung cancer. METHODS: We measured and compared the
      levels of CEA, SCC, Cyfra21-1 and NSE in BALF in 42 patients with peripheral lung
      cancer and 22 patients with benign lung disease. In the patients with peripheral
      lung cancer, the BAL was separately performed in the bronchus of the tumor
      bearing lung and in the corresponding bronchus of the opposite healthy lung.
      RESULTS: The levels of CEA, SCC, Cyfra21-1 and NSE were significantly elevated in
      BALF from the tumor-bearing lung compared with the opposite healthy lung in the
      lung cancer patients (P < 0.001) or the benign lung disease patients (P < 0.005).
      The diagnostic sensitivities of Cyfra21-1 (86 and 76%), with a specificity of
      91%, were the highest among the four tumor markers for the tumor-bearing lung
      versus the opposite healthy lung and benign lung disease. The combination of
      Cyfra21-1 and CEA increased the sensitivity to 93 and 86 percent, respectively.
      CONCLUSION: The assay of these tumor markers in BALF may be used as a diagnostic
      tool to complement a cytological examination in the diagnosis of peripheral lung
      cancer.

PMID- 23551360
TI  - A potential autocrine role for interferon tau in ovine trophectoderm.
AB  - Interferon tau (IFNT), a type I IFN produced by the conceptus trophectoderm, is
      the signal for maternal pregnancy recognition in ruminants. The purpose of this
      study was to investigate whether IFNT effected on the proliferation of ovine
      trophectoderm cells in an autocrine manner. Elongated ovine conceptuses (Days 15,
      Day 0 = day of mating) were collected for isolation of mononuclear ovine
      trophectoderm (oTr-1) cells, and conceptuses (Days 15 and 20, n = 4 and 3,
      respectively) were collected for RNA extraction. We demonstrated that the IFNT
      receptor, IFNAR1, was expressed in trophectoderm of day 15 and 20 conceptuses.
      Interestingly, the ovine trophectoderm cell line oTr-1 cultured in the presence
      of recombinant bovine IFNT (rbIFNT) displayed increased expressions of IFN
      stimulated genes (ISGs), such as IFN-stimulated gene 15 (ISG15), 2-5
      oligoadenylate synthetase 1 (OAS1) and bone marrow stromal cell antigen 2 (BST2).
      Meanwhile, the presence of rbIFNT in the culture media could promote the cell
      proliferation in a dose-dependent manner. Furthermore, the connective tissue
      growth factor, which has diverse functions in cell proliferation and is involved
      in conceptus elongation, was upregulated in oTr-1 cell by rbIFNT treatment in
      vitro. These data indicated that IFNT could act as an autocrine factor to
      regulate trophectoderm cell proliferation. 

PMID- 23551359
TI  - Budesonide/formoterol via Turbuhaler(r) versus formoterol via Turbuhaler(r) in
      patients with moderate to severe chronic obstructive pulmonary disease: phase III
      multinational study results.
AB  - BACKGROUND AND OBJECTIVE: The efficacy and tolerability of budesonide/formoterol
      versus formoterol in patients with moderate to severe chronic obstructive
      pulmonary disease (COPD) was evaluated. METHODS: In this randomized, double
      blind, parallel-group, phase III study (NCT01069289), patients with moderate to
      severe COPD for >=2 years received either budesonide/formoterol 160/4.5 MUg two
      inhalations twice daily via Turbuhaler(r) or formoterol 4.5 MUg two inhalations
      twice daily via Turbuhaler(r) for 12 weeks. Salbutamol was available as reliever
      medication. Primary outcome variable: change from baseline to average during
      treatment in pre-dose forced expiratory volume in 1 s (FEV1 ). RESULTS: One
      thousand two hundred ninety-three patients were randomized (budesonide/formoterol
      n = 636; formoterol n = 657). Both budesonide/formoterol and formoterol increased
      pre-dose FEV1 versus baseline (improvements of 4.6% and 1.5% over baseline,
      respectively), with the increase from baseline being significantly greater with
      budesonide/formoterol versus formoterol (budesonide/formoterol:formoterol ratio
      1.032; 95% confidence interval: 1.013-1.052; P = 0.0011). The
      budesonide/formoterol group had a significantly prolonged time to first
      exacerbation versus the formoterol group (hazard ratio: 0.679; 95% confidence
      interval: 0.507-0.909; P = 0.0094) and significantly greater improvements in many
      secondary outcome measures. Both treatments were well tolerated; the incidence
      and type of adverse events were similar: most commonly reported
      (budesonide/formoterol vs formoterol): COPD (8.0% vs 9.4%) and nasopharyngitis
      (5.5% vs 4.9%). CONCLUSIONS: Budesonide/formoterol 160/4.5 MUg two inhalations
      twice daily was effective and well tolerated in patients with moderate to severe
      COPD, offering benefits over formoterol alone in terms of improved lung function
      and reduced risk of exacerbation.

PMID- 23551361
TI  - Decreasing full-term neonatal birthweight over the past 2 decades in a single
      institute in Japan.
AB  - AIM: The aim of this study was to investigate whether full-term neonatal
      birthweight is decreasing or not. MATERIAL AND METHODS: Subjects were selected
      from the registration database of full-term singletons from a single local
      practitioner at two time-points, 1991 (n = 750) and 2011 (n = 442). Maternal age,
      parity, and smoking habits were recorded. Baseline characteristics included pre
      pregnancy bodyweight (BW), body mass index (BMI), bodyweight before parturition,
      and weight gain during pregnancy. Neonatal birthweight and height were recorded.
      Variables correlated with neonatal size were investigated. RESULTS: Male
      birthweight decreased from 3248 +/- 409 (n = 373) to 3149 +/- 430 g (n = 230) (P
      < 0.001). Female birthweight also decreased from 3148 +/- 378 (n = 377) to 3063
      +/- 343 g (n = 212) (P < 0.01). Gestational age was shorter (40.1 +/- 1.1 to 39.6
      +/- 1.1 weeks, P < 0.001). Pre-pregnancy maternal BMI did not change (20.7 +/-
      2.6, n = 750 to 20.5 +/- 2.7, n = 442). Weight gain during pregnancy decreased
      (11.3 +/- 3.8 to 10.8 +/- 3.4 kg, P < 0.05) and was positively correlated with
      birthweight (P < 0.001). On multiple regression analysis, time was inversely
      correlated with birthweight, while it was positively correlated with pre
      pregnancy BMI, weight gain during pregnancy, and gestational age. CONCLUSIONS: In
      addition to maternal slenderness, increasing lower weight gain during pregnancy
      and medical intervention by physicians may in part contribute to the decrease in
      full-term birthweight over the past 2 decades.

PMID- 23551362
TI  - A case of an allergic reaction to a spinal cord stimulator: identification of the
      antigen with epicutaneous patch testing, allowing successful reimplantation.

PMID- 23551363
TI  - Coexistence of marginal zone cutaneous B-cell lymphoma and classic Hodgkin
      disease: does a biological relationship exist?
AB  - The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the
      same patient, although previously reported, is very unusual. This situation is
      extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if
      there is no personal background of cytostatic treatment. We report a 44-year-old
      man who developed cutaneous nodules over a period of two years. A marginal zone
      cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the
      lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.

PMID- 23551364
TI  - Introduction for understanding and treating itch.

PMID- 23551365
TI  - Understanding the pathophysiology of itch.
AB  - Itch is the most common symptom described by our patients. Treating this symptom
      can be challenging. A revolution is ongoing in understanding the pathophysiology
      of itch and will allow this challenge to be met. The present authors review and
      update the current understanding of the pathophysiology of itch.

PMID- 23551366
TI  - Advanced aging skin and itch: addressing an unmet need.
AB  - Itch is the most common skin disorder in the elderly and frequently diminishes
      quality of life in this population. The high prevalence of pruritus in elderly
      patients is attributed in part to the decline in the normal physiology of the
      advanced aging skin, and reflects poor hydration, impaired skin barrier, and
      altered neural function, all ultimately contributing to inflammation and
      pruritus. As the elderly population continues to grow, practitioners need to be
      aware of how to evaluate and manage pruritus, recognizing the common conditions
      contributing to itch in elderly patients as well as the challenges of treatment
      in this group. Ultimately, management of pruritus will require an individually
      tailored approach that is guided by a patient's general health, severity of
      symptoms, and the potential adverse effects of itch therapies.

PMID- 23551367
TI  - Neuropathic itch: diagnosis and management.
AB  - Chronic pruritus (CP) is a frequent symptom in the general population; in 8% of
      all patients, it has a neuropathic origin. CP is of neuropathic origin when nerve
      fiber damage is responsible for the symptom. The damage can be caused by
      compression or degeneration of the nerve fibers in the skin or extracutaneous in
      peripheral nerves or the central nervous system. There are significant
      differences in the pathogenesis and in the clinical presentation of neuropathic
      CP. Localized neuropathic CP such as brachioradial pruritus or notalgia
      paresthetica are due to a circumscribed nerve compression and are often limited
      on the corresponding dermatome. In contrast, generalized neuropathic CP, as in
      small fiber neuropathies, may be associated with a systemic or metabolic
      underlying disease. It is not always easy to establish the diagnosis because a
      variety of diseases can be responsible for this type of CP. The present study
      shows an overview of possible diseases, diagnostic tools, and the relevant
      therapy strategies.

PMID- 23551369
TI  - Practical guidelines for the use of steroid-sparing agents in the treatment of
      chronic pruritus.
AB  - Chronic pruritus in the adult patient is both an underappreciated and a difficult
      to treat condition. In the vast majority of cases, itch is the result of
      inflammatory skin disease and therefore may be responsive to systemic anti
      inflammatory therapies. Urticarial dermatitis is an under-recognized cause of
      chronic itch in the adult population. Patients with this disorder are
      characterized by prolonged, prednisone-responsive pruritus, often in the absence
      of substantial cutaneous findings. Skin findings, when present, can range from
      subtle, persistent urticarial lesions to excoriated papules, often intermixed
      with urticaria, eczematous change, and lichenification secondary to chronic
      scratching. Hereby, we describe our algorithm for evaluation and management of
      adult patients with refractory pruritus (urticarial dermatitis in particular),
      including evaluation for other etiologies of pruritus, pre-immunosuppression
      workup, and the use of azathioprine and other steroid-sparing agents for
      treatment of recalcitrant itch.

PMID- 23551368
TI  - The effects of treatment on itch in atopic dermatitis.
AB  - Pruritus causes significant impairment in the quality of life of patients
      suffering from atopic dermatitis. Treatments for itch in atopic dermatitis range
      from simple avoidance of pruritus triggers to more complicated systemic therapy.
      Several treatments aim to target specific mediators of itch in atopic dermatitis,
      whereas others improve pruritus by reducing inflammation. Currently the most
      effective treatments for atopic dermatitis-associated itch are primarily topical
      or systemic anti-inflammatory agents. Better management of pruritus in atopic
      dermatitis is an important goal and necessitates the development of novel
      targeted treatments as well as efficient use of current therapies.

PMID- 23551370
TI  - Pruritus to anticancer agents targeting the EGFR, BRAF, and CTLA-4.
AB  - In the past decade, the expanded use of targeted anticancer drugs has
      significantly prolonged survival in patients treated for a variety of cancers.
      Despite their increased specificity, agents such as epidermal growth factor
      receptor inhibitors (EGFRIs), BRAF inhibitors, and targeted immunotherapies have
      commonly been associated with a number of dermatologic adverse events, often
      necessitating treatment modifications and negatively impacting patients' quality
      of life. Although toxicities such as rash and xerosis are frequently discussed,
      symptomatic pruritus, or itch, has emerged as an important, and frequently
      neglected, event. The present study reviews the incidence and clinical
      presentation of pruritus with the EFGRIs, and with two novel anti-melanoma drugs,
      vemurafenib and ipilimumab, with a focus on the putative underlying
      pathophysiology, and current management strategies.

PMID- 23551371
TI  - Complementary integrative approach for treating pruritus.
AB  - Complementary and alternative medicine (CAM) is a conservative and increasingly
      popular approach to treat pruritus for both patients and medical providers. CAM
      includes natural products, mind-body medicine, and manipulative and body-based
      practices. In this overview, we summarize current evidence, possible mechanisms
      and clinical approaches for treating pruritus with CAM techniques. We focus on
      pruritus associated with atopic dermatitis, herpes zoster, chronic urticaria,
      burns, and postoperative contexts where the evidence for CAM approaches is
      promising.

PMID- 23551372
TI  - Female-specific pruritus from childhood to postmenopause: clinical features,
      hormonal factors, and treatment considerations.
AB  - There have been considerable advances in our understanding of the pathophysiology
      of pruritus in recent years. The purpose of this review was to highlight itch
      entities in women, and in particular pruritic vulvar dermatoses that women
      experience among different age groups. Unique temporal shifts may contribute to
      the etiology of many of these conditions. These changes lead to cyclical changes
      in the skin's basic composition. Specifically, estrogen receptors have been
      detected on keratinocytes that respond to rising and falling levels of estrogen.
      These receptors lead to changes in skin hydration, collagen content, and in the
      concentration of glycosaminoglycans that form the skin barrier. In addition,
      hormonal pH changes associated with the menstrual cycle may be an important
      factor in the aggravation of itch as increasing pH is known to activate the
      proteinase-activated receptor-2, a well-known itch mediator. Common pruritic
      conditions in women that will be discussed include atopic and irritant
      dermatitis, psoriasis, lichen sclerosus, infectious vulvovaginitis, vulvovaginal
      candidiasis, atrophic vulvovaginitis, squamous cell carcinoma, lichen simplex
      chronicus, and neuropathic itch. We also examine pruritic conditions associated
      with pregnancy including pemphigoid gestationis, polymorphic eruption of
      pregnancy, intrahepatic cholestasis of pregnancy and atopic eruption of
      pregnancy. Finally, acceptable and contraindicated antipruritic agents in
      pregnancy are examined.

PMID- 23551373
TI  - Simple, easy, and still effective treatment option in severe rhinophyma: shave
      and paste.
AB  - A 74-year-old man suffering from severe rhinophyma with breathing difficulty and
      depression seeking for help presented to our clinic. The cauliflower-like mass
      was full thickness excised and a full thickness skin graft from right inguinal
      region was applied. An exceptionally treatment and satisfactory cosmetic result
      was obtained in single stage.

PMID- 23551374
TI  - Methyl - aminolevulinic acid photodynamic therapy and topical tretinoin in a
      patient with vulvar extramammary Paget's disease.
AB  - Extramammary Paget's disease is a rare neoplasm of apocrine gland-bearing areas
      of the skin. The most common site of presentation is the vulva. Surgery is the
      most frequently reported therapy so far; however, it is invasive and it is
      complicated by a high rate of recurrence. For this reason, several less-invasive
      treatments have been recently proposed, including photodynamic therapy. We
      describe in this article the case of an 84-year-old patient with a noninvasive
      vulvar extramammary Paget's disease successfully treated with methyl
      aminolevulinic acid photodynamic therapy associated with topical tretinoin.

PMID- 23551375
TI  - Pruritic papular eruption in HIV: a case successfully treated with NB-UVB.
AB  - Pruritic papular eruption (PPE) is a skin disease characterized by the eruption
      of itching papules on the extremities, face, and trunk; it is quite frequent in
      HIV-positive patients especially during the advanced immunosuppressive stage. PPE
      usually improves or heals when antiretroviral therapy restores the immune system
      function, but in some cases, it can take several months, and a symptomatic
      treatment for PPE is required. Systemic antihistamines, topical steroids, topical
      tacrolimus, itraconazole, pentoxyphilline, and ultraviolet B phototherapy have
      been proposed in cases of persisting PPE, but an elective treatment has not yet
      been found. We describe the case of a black patient affected by PPE, nonimproving
      with antiretroviral treatment, and resistant to topical steroids and oral
      antihistamines; a satisfactory and speedy result was achieved with narrow-band
      ultraviolet B phototherapy.

PMID- 23551376
TI  - Diffuse cutaneous bullous mastocytosis in a newborn.
AB  - Diffuse cutaneous mastocytosis is the rarest subtype of mastocytosis among those
      that affect children. A 7-month-old girl presented at birth dry and thickened
      skin. On the second day of life, tense blisters appeared on erythrodermic areas
      and during the next days spread over the face, trunk, and limbs. The skin was
      bright red, had a "peau d'orange" appearance, and was considerably thickened with
      numerous translucent and hemorrhagic blisters. A skin biopsy revealed massive
      infiltration of the dermis with mast cells, leading to the diagnosis of diffuse
      erythrodermic mastocytosis. Systemic corticosteroids were given along with
      antihistamines with good results. Despite the progresses in the understanding of
      pathogenesis, genetics, and diagnostic criteria of mastocytosis, clear and
      reliable prognostic markers are still lacking, especially in order to predict
      systemic involvement. not only in diffuse but also in the commoner forms of the
      disease.

PMID- 23551377
TI  - Abstracts of the 19th Annual Conference of the British HIV Association (BHIVA).
      Manchester, United Kingdom. April 16-19, 2013.

PMID- 23551378
TI  - Percutaneous transhepatic venous access for ICD implantation in a patient with
      Ebstein's anomaly with ventricular tachycardia post-Glenn operation.

PMID- 23551379
TI  - RADseq underestimates diversity and introduces genealogical biases due to
      nonrandom haplotype sampling.
AB  - Reduced representation genome-sequencing approaches based on restriction
      digestion are enabling large-scale marker generation and facilitating genomic
      studies in a wide range of model and nonmodel systems. However, sampling
      chromosomes based on restriction digestion may introduce a bias in allele
      frequency estimation due to polymorphisms in restriction sites. To explore the
      effects of this nonrandom sampling and its sensitivity to different evolutionary
      parameters, we developed a coalescent-simulation framework to mimic the biased
      recovery of chromosomes in restriction-based short-read sequencing experiments
      (RADseq). We analysed simulated DNA sequence datasets and compared known values
      from simulations with those that would be estimated using a RADseq approach from
      the same samples. We compare these 'true' and 'estimated' values of commonly used
      summary statistics, pi, theta(w), Tajima's D and F(ST). We show that loci with
      missing haplotypes have estimated summary statistic values that can deviate
      dramatically from true values and are also enriched for particular genealogical
      histories. These biases are sensitive to nonequilibrium demography, such as
      bottlenecks and population expansion. In silico digests with 102 completely
      sequenced Drosophila melanogaster genomes yielded results similar to our findings
      from coalescent simulations. Though the potential of RADseq for marker discovery
      and trait mapping in nonmodel systems remains undisputed, our results urge
      caution when applying this technique to make population genetic inferences.

PMID- 23551380
TI  - A real-time assessment of factors influencing medication events.
AB  - Reducing medical error is critical to improving the safety and quality of
      healthcare. Physician stress, fatigue, and excessive workload are performance
      shaping factors (PSFs) that may influence medical events (actual administration
      errors and near misses), but direct relationships between these factors and
      patient safety have not been clearly defined. This study assessed the real-time
      influence of emotional stress, workload, and sleep deprivation on self-reported
      medication events by physicians in academic hospitals. During an 18-month study
      period, 185 physician participants working at four university-affiliated teaching
      hospitals reported medication events using a confidential reporting application
      on handheld computers. Emotional stress scores, perceived workload, patient case
      volume, clinical experience, total sleep, and demographic variables were also
      captured via the handheld computers. Medication event reports (n = 11) were then
      correlated with these demographic and PSFs. Medication events were associated
      with 36.1% higher perceived workload (p < .05), 38.6% higher inpatient caseloads
      (p < .01), and 55.9% higher emotional stress scores (p < .01). There was a trend
      for reported events to also be associated with less sleep (p = .10). These
      results confirm the effect of factors influencing medication events, and support
      attention to both provider and hospital environmental characteristics for
      improving patient safety. 

PMID- 23551381
TI  - Functional aging impairs the role of feedback in motor learning.
AB  - AIM: Optimal motor skill acquisition frequently requires augmented feedback or
      knowledge of results (KR). However, the effect of functional declines on the
      benefits of KR remains to be determined. The objective of this research was to
      examine how cognitive and motor deficits of older adults influence the use of KR
      for motor skill learning. METHODS: A total of 57 older adults (mean 73.1 years;
      SD 4.2) received both cognitive and eye-hand coordination assessments, whereas 55
      young controls (mean 25.8 years; SD 3.8) took only the eye-hand coordination
      test. All young and older participants learned a time-constrained arm movement
      through KR in three pre-KR and post-KR intervals. RESULTS: In the subsequent no
      KR skill retests, absolute and variable time errors were not significantly
      reduced for the older learners who had KR during skill practice, especially for
      those with cognitive and motor dysfunctions. The finding suggests that KR results
      in no measureable improvement for older adults with cognitive and motor
      functional deficiencies. More importantly, for the older adults, longer post-KR
      intervals showed greater detrimental effects on feedback-based motor learning
      than shorter pauses after KR delivery. DISCUSSION: The findings support the
      hypothesis about the effects of cognitive and motor deficits on KR in motor skill
      learning of older adults. The dynamics of cognitive and motor aging, external
      feedback and internal control mechanisms collectively explain the deterioration
      in the sensory-motor learning of older adults. The theoretical implications and
      practical relevance of functional aging for motor skill learning are discussed.

PMID- 23551382
TI  - Clinical feasibility of a new through-the-scope fully covered esophageal self
      expandable metallic stent: an in vivo animal study.
AB  - BACKGROUND: Most delivery devices used for esophageal stents for obstructing
      esophageal cancer have a diameter of 5-8 mm, a size that is too large to pass
      through the endoscopic working channel. The conventional esophageal stent
      requires multiple endoscopic procedures for implantation. The purpose of the
      present study was to evaluate the clinical feasibility of a newly developed fully
      covered, self-expanding, through-the-scope (TTS) esophageal stent in a porcine
      model. METHODS: Eight mini pigs were used. Each animal underwent placement of a
      fully covered TTS stent (Hanarostent(r) Esophagus TTS) and the upper part of the
      stent was fixed by suturing with nylon. Fluoroscopy was carried out every week to
      assess migration of the stent. Follow-up endoscopy was done every month for 3
      months to evaluate the status of the membrane, stent mesh, grade of tissue
      hyperplasia, and mucosal changes at both ends of the stent. RESULTS: All stents
      were successfully and easily deployed, and were placed without any distortion in
      the stent or without rupture of the membrane. In two cases, stent migration was
      observed after 8 weeks. No case of membrane disruption, stent mesh disruption or
      tissue hyperplasia at either end of the stent was found at the completion of the
      study. CONCLUSION: Our findings indicate that the new fully covered self
      expanding TTS esophageal stent is easy and simple to implant, and no significant
      distortion of mesh or disruption of membrane was observed.

PMID- 23551383
TI  - Evaluation of association between atherogenic index of plasma and intima-media
      thickness of the carotid artery for subclinic atherosclerosis in patients on
      maintenance hemodialysis.
AB  - Incidence of cardiovascular diseases in the patients having chronic kidney
      disease (CKD) is between 25% and 60%. This increased rate is proposed to be
      associated with "accelerated atherosclerosis." Increased carotid intima-media
      thickness (CIMT) is a subclinical atherosclerosis marker. Small-dense low-density
      lipoprotein particles are a strong risk factor for atherosclerosis. It was shown
      that atherogenic index of plasma (AIP = log(TG/HDL-c)) is correlated with size of
      the lipoprotein particles. We investigated the correlation between AIP and CIMT
      which is a subclinical atherosclerosis marker, in hemodialysis (HD) patients. A
      total of 62 persons with 31 patients under HD therapy and 31 volunteers were
      included in the study. In all the participants, CIMT was measured and AIP were
      calculated. AIP and CIMT values of the participants were compared with blood
      pressures, lipid profiles and the other risk factors. AIP (0.39 +/- 0.32) and
      CIMT (0.57 +/- 0.13) were found significantly higher in the patient group than in
      the controls (0.04 +/- 0.36 and 0.45 +/- 0.119, respectively); (P = 0.0001 and
      0.0001, respectively). There was a significant correlation between AIP and
      increased CIMT in the patient group (P = 0.0001, r = 0.430). Among the lipid
      parameters, the strongest correlation was found between CIMT and AIP. We
      demonstrated the significant increase of AIP and CIMT in HD patients. A
      correlation was found between AIP and CIMT. AIP was found to show a correlation
      with a greater number of risk factors, both classical and CKD specific, than
      CIMT. These data suggest that AIP might be a method which can be used both in
      diagnosis of subclinical atherosclerosis and in deceleration processes of its
      progression. 

PMID- 23551384
TI  - Association between awareness of harmful effects of smoking and smoking cessation
      advice provided by hospital chest physicians in Guangzhou, China: a multi
      institutional cross-sectional survey.
AB  - BACKGROUND AND OBJECTIVE: It is unknown which factors are associated with smoking
      cessation interventions initiated by hospital chest physicians in China. We
      examined physicians' awareness of negative effects of smoking on smoking
      cessation advice given. METHODS: A cluster randomized cross-sectional survey was
      conducted from July to August 2011 in hospital chest physicians (n = 354) in
      Guangzhou, China. RESULTS: Of those who responded (n = 354, 92%), 63.8% were
      aware of negative effects of smoking and 64.5% initiated smoking cessation
      programmes with their patients. Awareness differed among physicians depending on
      their hospital affiliation (chi(2)  = 54.7, P > 0.001), that is, primary (44.9%),
      secondary (55.1%) and tertiary hospitals (87.0%), (odds ratio = 1.732, 95%
      confidence interval: 1.072-2.797, P < 0.05). Physicians with less awareness
      prescribed smoking cessation medication less frequently (chi(2)  = 137.71, P <
      0.001). Smoking cessation practice by physicians also depended on hospital
      affiliation (chi(2)  = 5.7, P > 0.001), (odds ratio = 4.074, 95% confidence
      interval: 1.399-11.860, P = 0.010). Smoking status of physicians was related to
      smoking cessation practice. CONCLUSIONS: Physicians more aware of the health
      hazards of smoking provided more smoking cessation advice. Awareness correlated
      with hospital levels and smoking status. Physician's advice correlated with their
      smoking status and educational background, but not with the levels of hospital,
      position or department affiliation.

PMID- 23551386
TI  - Integration and reuse in cognitive skill acquisition.
AB  - Previous accounts of cognitive skill acquisition have demonstrated how procedural
      knowledge can be obtained and transformed over time into skilled task
      performance. This article focuses on a complementary aspect of skill acquisition,
      namely the integration and reuse of previously known component skills. The
      article posits that, in addition to mechanisms that proceduralize knowledge into
      more efficient forms, skill acquisition requires tight integration of newly
      acquired knowledge and previously learned knowledge. Skill acquisition also
      benefits from reuse of existing knowledge across disparate task domains, relying
      on indexicals to reference and share necessary information across knowledge
      components. To demonstrate these ideas, the article proposes a computational
      model of skill acquisition from instructions focused on integration and reuse,
      and applies this model to account for behavior across seven task domains. 

PMID- 23551385
TI  - PIN6 is required for nectary auxin response and short stamen development.
AB  - The PIN family of proteins is best known for its involvement in polar auxin
      transport and tropic responses. PIN6 (At1g77110) is one of the remaining PIN
      family members in Arabidopsis thaliana to which a biological function has not yet
      been ascribed. Here we report that PIN6 is a nectary-enriched gene whose
      expression level is positively correlated with total nectar production in
      Arabidopsis, and whose function is required for the proper development of short
      stamens. PIN6 accumulates in internal membranes consistent with the ER, and
      multiple lines of evidence demonstrate that PIN6 is required for auxin-dependent
      responses in nectaries. Wild-type plants expressing auxin-responsive DR5:GFP or
      DR5:GUS reporters displayed intense signal in lateral nectaries, but pin6 lateral
      nectaries showed little or no signal for these reporters. Further, exogenous
      auxin treatment increased nectar production more than tenfold in wild-type
      plants, but nectar production was not increased in pin6 mutants when treated with
      auxin. Conversely, the auxin transport inhibitor N-1-naphthylphthalamic acid
      (NPA) reduced nectar production in wild-type plants by more than twofold, but had
      no significant effect on pin6 lines. Interestingly, a MYB57 transcription factor
      mutant, myb57-2, closely phenocopied the loss-of-function mutant pin6-2. However,
      PIN6 expression was not dependent on MYB57, and RNA-seq analyses of pin6-2 and
      myb57-2 mutant nectaries showed little overlap in terms of differentially
      expressed genes. Cumulatively, these results demonstrate that PIN6 is required
      for proper auxin response and nectary function in Arabidopsis. These results also
      identify auxin as an important factor in the regulation of nectar production, and
      implicate short stamens in the maturation of lateral nectaries.

PMID- 23551387
TI  - Periocular granuloma annulare: a case report and review of literature.
AB  - Granuloma annulare (GA) is a granulomatous dermatosis that rarely presents on the
      face and is extremely uncommon in the periocular region. We report our experience
      with the presentation and management of GA lesions on the eyelids of a 17-year
      old girl. We performed a review of published literature and identified 13 cases
      of pediatric periocular GA. One additional case was identified upon review of all
      pediatric GA cases at the Cleveland Clinic Foundation. Review of these cases
      suggests that periocular GA is a benign condition that spontaneously regresses
      within a few months. GA nodules have a predilection for the upper eyelids. A
      greater incidence is noted in African American children. Awareness of the self
      resolving nature of this condition can prevent unnecessary surgical excisions in
      affected children. 

PMID- 23551388
TI  - Primary pleural epithelioid hemangioendothelioma compressing the myocardium.
AB  - Epithelioid haemangioendothelioma (EH) is a rare malignant tumor of vascular
      origin that usually arises in bone, liver, soft tissue, or lung. EH originating
      in the pleura has been less frequently described. We describe an uncommon case of
      pleural EH compressing the myocardium in a 39-year-old woman. The patient was
      diagnosed with pleural EH confirmed by surgery and immunohistochemistry. She
      sustained stable disease 14 months after the diagnosis and her symptoms improved
      after systemic chemotherapy with carboplatine and etoposide. Complete surgical
      excision of pleural EH followed chemotherapy may prolong survival.

PMID- 23551389
TI  - Association of Streptococcus bovis endocarditis and advanced colorectal
      neoplasia: a case-control study.
AB  - OBJECTIVE: To study the association between Streptococcus bovis (S. bovis)
      endocarditis and advanced colorectal neoplasia. METHODS: This was a case-control
      study of patients with S. bovis endocarditis undergoing colonoscopic evaluation.
      Patients were matched 1:20 with controls by gender and age (+/-2 years) from a
      large screening colonoscopy database. The baseline, colonoscopic and
      clinicopathological characteristics of patients with S. bovis endocarditis were
      analyzed. RESULTS: From 1996 to 2010, 18 adult patients with S. bovis bacteremia
      were identified, of whom 10 with infective endocarditis (IE) underwent
      colonoscopic evaluation. Endocarditis involved a native or prosthetic valve in
      six and four of those patients, respectively. All 10 patients recovered without
      recurrence of IE (mean follow-up duration 49.6 months). None had a concurrent or
      preceding history of colon disease and only one had subclinical chronic liver
      disease. Advanced neoplasia, defined as the presence of polyps >=1 cm (n = 6),
      villous histology (n = 3), high-grade focal dysplasia (n = 1) or cancer (n = 1),
      was found under colonoscopy in 6 of the 10 cases (60.0%) compared with 13/200
      (6.5%) matched controls (OR 21.6, 95% CI 5.4-86.1, P < 0.0001). CONCLUSIONS: S.
      bovis endocarditis is strongly associated with the presence of advanced
      colorectal neoplasia. In the absence of any contraindication, colonoscopic
      examination is strongly recommended in patients with endocarditis. The exact
      pathophysiological mechanisms underlying this association and the predilection
      for S. bovis bacteremia in patients with advanced colonic neoplasia remain
      unclear.

PMID- 23551390
TI  - A randomized and controlled clinical trial of two different compositions of
      deproteinized bovine bone and autogenous bone used for lateral ridge
      augmentation.
AB  - OBJECTIVE: The aim of the study was to radiologically and histologically evaluate
      the graft healing and volumetric changes after lateral augmentation with two
      different compositions of deproteinized bovine bone (DPBB) and autogenous bone
      (AB). MATERIAL AND METHODS: Thirteen patients with a mean age of 59.6 +/- 12.1
      years (six men and seven women) were included in this randomized and controlled
      trial, designed as a split-mouth study. Ten edentulous and four partially
      edentulous jaws with an alveolar ridge width of <=4 mm were laterally augmented
      with a graft composition of 60 : 40 (DPBB/AB) on one side and 90 : 10 (DPBB/AB)
      on the contralateral side. Cone beam computed tomography (CB/CT) was obtained
      immediately postoperatively and after a healing period of 7.5 months. Width
      changes were measured on CB/CT scans. After a mean healing period of 8.1 months
      (range, 7.9-8.3), biopsies were retrieved perpendicular to the crest from each
      graft by means of a trephine bur. Histomorphometry was performed, and the
      following variables were recorded: Ingrowth of new bone (percentage of total
      graft width), percentage of DPBB, bone and soft tissue, and percentage of DPBB
      particles in contact with bone. RESULTS: The mean gained width of the alveolar
      crest after 7.5 months was significantly more for the 60 : 40 mixture compared
      with the 90 : 10 mixture, 3.5 (+/-1.3) mm and 2.9 (+/-1.3) mm, respectively.
      There was a significant difference in graft width reduction between 60 : 40 and
      90 : 10 after 7.5 months, 37 (+/-19.9)% and 46.9 (+/-23.5)%, respectively. New
      bone ingrowth had occurred in 82.1 (+/-23.3)% and 82.3 (+/-26.6)% of the graft,
      respectively. There were no statistical differences between fractions of
      different tissues between the 90 : 10 and 60 : 40 compositions. However, there
      were significantly more soft tissue and less new bone formation closer to the
      periosteum compared with the graft portion closer to the residual bone in both 60
      : 40 and 90 : 10 compositions. CONCLUSIONS: There was significantly less graft
      width reduction with a mixture of 60 : 40 (DPBB/AB) compared with a mixture of 90
      : 10 composition, but the results from the histomorphometry showed no statistical
      differences comparing the groups.

PMID- 23551391
TI  - Fruit and vegetable intake and prostate cancer risk: a meta-analysis.
AB  - AIMS: Recent reports have examined the effect of fruit and vegetable intake on
      the risk of prostate cancer, but the results are inconsistent. A meta-analysis of
      prospective studies was conducted to arrive at quantitative conclusions about the
      contribution of vegetable and fruit intake to the incidence of prostate cancer.
      METHODS: A comprehensive, systematic search of medical literature published up to
      June 2012 was performed to identify relevant studies. Separate meta-analyses were
      conducted for fruit and vegetable consumption. The presence of publication bias
      was assessed using Egger and Begg tests. RESULTS: In total, 16 cohort studies met
      the inclusion criteria and were included in the meta-analysis. The combined
      adjusted relative risk comparing highest with lowest categories showed that there
      was no association between vegetable and fruit consumption and prostate cancer
      incidence. The pooled relative risk was 0.97 (95%CI 0.93, 1.01) for vegetables
      and 1.02 (95%CI 0.98, 1.07) for fruit. There is no heterogeneity between the
      studies. No publication bias was detected. CONCLUSION: This meta-analysis
      suggests that total fruit or vegetable consumption may not exert a protective
      role in the risk of prostate cancer.

PMID- 23551393
TI  - Clinical trial recruitment--a complex intervention?
AB  - AIMS AND OBJECTIVES: To discuss the evidence of poor recruitment rates in
      randomised clinical trials and relate this to existing recruitment methodology
      before a novel approach to recruitment is suggested. BACKGROUND: Recruitment is
      crucial to the success of research projects. Effective recruitment leads to
      effective retention, an increased pool of data and in-time completion of
      projects. Robust evidence indicates that recruitment remains a challenge in many
      clinical trials. DESIGN: Discursive article. METHODS: The complexity of
      recruitment is mandated based on the findings from a literature review that
      summarises common threats to successful recruitment. Nursing theories and models
      that incorporate recruitment are critically reviewed before recruiting, and its
      planning is related to existing complex intervention methodology. CONCLUSION:
      Threats to sufficient recruitment are inherent in the planning of studies, the
      recruiting process and triadic relationships between institutions, recruiter and
      participants. Existing nursing theories and models address important recruitment
      issues but do not account for all aspects that jeopardise sufficient recruitment.
      Hence, available frameworks for complex intervention planning and evaluation are
      useful to guide recruitment and its planning as an umbrella methodology.
      RELEVANCE TO CLINICAL PRACTICE: Using complex intervention methodology for
      recruitment and its planning enhances a nurse researcher's awareness of the
      challenges and pitfalls recruitment poses and may translate to improved
      recruitment rates and overall success of clinical trials.

PMID- 23551392
TI  - Mechanical regulation of epigenetics in vascular biology and pathobiology.
AB  - Vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) are constantly
      exposed to haemodynamic forces, including blood flow-induced fluid shear stress
      and cyclic stretch from blood pressure. These forces modulate vascular cell gene
      expression and function and, therefore, influence vascular physiology and
      pathophysiology in health and disease. Epigenetics, including DNA methylation,
      histone modification/chromatin remodelling and RNA-based machinery, refers to the
      study of heritable changes in gene expression that occur without changes in the
      DNA sequence. The role of haemodynamic force-induced epigenetic modifications in
      the regulation of vascular gene expression and function has recently been
      elucidated. This review provides an introduction to the epigenetic concepts that
      relate to vascular physiology and pathophysiology. Through the studies of gene
      expression, cell proliferation, angiogenesis, migration and pathophysiological
      states, we present a conceptual framework for understanding how mechanical force
      induced epigenetic modifications work to control vascular gene expression and
      function and, hence, the development of vascular disorders. This research
      contributes to our knowledge of how the mechanical environment impacts the
      chromatin state of ECs and VSMCs and the consequent cellular behaviours.

PMID- 23551394
TI  - Community health workers - a resource for identification and referral of sick
      newborns in rural Uganda.
AB  - OBJECTIVE: To determine community health workers' (CHWs) competence in
      identifying and referring sick newborns in Uganda. METHODS: Case-vignettes,
      observations of role-plays and interviews were employed to collect data using
      checklists and semistructured questionnaires, from 57 trained CHWs participating
      in a community health facility-linked cluster randomised trial. Competence to
      identify and refer sick newborns was measured by knowledge of newborn danger
      signs, skills to identify sick newborns and effective communication to mothers.
      Proportions and median scores were computed for each attribute with a pre-defined
      pass mark of 100% for knowledge and 90% for skill and communication. RESULTS: For
      knowledge, 68% of the CHWs attained the pass mark. The median percentage score
      was 100 (IQR 94 100). 74% mentioned the required five newborn danger signs
      unprompted. 'Red umbilicus/cord with pus' was mentioned by all CHWs (100%), but
      none mentioned chest in-drawing and grunting as newborn danger signs. 63%
      attained the pass mark for both skill and communication. The median percentage
      scores were 91 (IQR 82 100) for skills and 94 (IQR 89, 94) for effective
      communication. 98% correctly identified the four case-vignettes as sick or not
      sick newborn. 'Preterm birth' was the least identified danger sign from the case
      vignettes, by 51% of the CHWs. CONCLUSION: CHWs trained for a short period but
      effectively supervised are competent in identifying and referring sick newborns
      in a poor resource setting.

PMID- 23551395
TI  - Intention to adhere to HIV treatment: a patient-centred predictor of
      antiretroviral adherence.
AB  - OBJECTIVES: Despite the effectiveness of highly active antiretroviral therapy
      (HAART), HIV remains a major cause of mortality in the USA, largely as a result
      of poor HIV treatment adherence. In this study we assessed the association
      between five patient-centred factors and adherence to HIV treatment. METHODS: We
      surveyed 244 adults at two HIV clinics in Houston, Texas between October 2009 and
      April 2010. Participants were given a questionnaire and their charts were
      reviewed for clinical data. Survey items assessed the following factors: self
      assessed HIV knowledge, awareness of disease biomarkers, intention to adhere to
      HIV treatment, health literacy and decision-making style. The primary outcome
      measure was HAART adherence during the previous month. Logistic regressions were
      performed to calculate the effect of each factor on adherence. RESULTS: All
      participants had HIV/AIDS and were on HAART at enrolment. Eight per cent of
      participants were female, 57% were African-American and 16% were Hispanic. Mean
      age was 58.1 years. Sixty-eight per cent were adherent to HAART during the last
      month. On univariate analysis, a preference for wanting choices, correct
      knowledge of recent HIV viral load level, and intention to adhere to HIV
      treatment were significantly associated with adherence. On multivariate analysis,
      only intention to adhere to HIV treatment remained statistically significant
      after adjusting for other factors (odds ratio 2.2; 95% confidence interval 1.1 to
      4.3). CONCLUSIONS: Intention to adhere to HIV treatment was significantly
      associated with self-reported adherence to HAART. Interventions that bolster
      patients' intentions to adhere to HIV treatment during clinical encounters may
      improve adherence to HAART and HIV control.

PMID- 23551396
TI  - Study of living kidney donor-recipient relationships: variation with
      socioeconomic deprivation in the white population of England.
AB  - BACKGROUND: Socioeconomic deprivation is associated with higher renal replacement
      therapy acceptance rates in the UK but lower rates of living kidney
      transplantation. This study examines donor-recipient relationship patterns with
      socioeconomic deprivation in the white population of England. METHODS:
      Demographic characteristics of all white live renal transplant donors and
      recipients between 2001 and 2010 in England were analyzed. Patterns of donor
      recipient relationship were analyzed to see whether they differed according to an
      ecological measure of socioeconomic status (Index of Multiple Deprivation). Group
      comparisons were performed using chi-square tests and multivariable logistic
      regression. RESULTS: Sources of living kidney transplants differed with
      deprivation (p < 0.001). Recipients living in poorer areas were more likely to
      receive a kidney from a sibling, child, and "other relative" donor and less
      likely from spouses/partners. Logistic regression suggested differences seen with
      spouse/partner donations with deprivation were explained by differences in the
      age and gender of the recipients. CONCLUSIONS: The source of living kidneys
      differs by level of area deprivation. Given the disparity in rates of living
      kidney transplants between the most and least socioeconomically deprived, there
      is a need to understand the reasons behind these observed relationship
      differences, with the aim of increasing transplantation rates in the most
      deprived.

PMID- 23551397
TI  - Reduced dose cyclophosphamide, fludarabine and antithymocyte globulin for sibling
      and unrelated transplant of children with severe and very severe aplastic anemia.
AB  - We evaluated the results of a novel conditioning regimen of reduced dose
      cyclophosphamide (Cy, 25 mg/kg for four days), fludarabine (Flu, 30 mg/m(2) for
      four days), and rabbit ATG (2.5 mg/kg for three days) for allogeneic transplant
      of children with SAA, implemented since January 2009. Overall, 23 patients were
      treated with this regimen (16 male, seven female), including 10 diagnosed with
      VSAA. Donors included eight-MSD and 15 UD (five-matched UD, and 10 mismatched
      UD). All patients showed neutrophil and platelet engraftment. Cumulative
      incidence of acute (grade 2 or above) and chronic GVHD was 26.1% and 8.7%,
      respectively. Estimated two-yr FFS and OS for the entire cohort was 90.3 +/-
      6.5%. Rates of TRM and graft failure were 5.3% and 4.3%, respectively. No
      difference in OS was found according to disease severity (SAA vs. VSAA, p =
      0.184), or according to donor type (MSD vs. UD, p = 0.699). Excellent outcomes of
      patients with VSAA underscore the efficacy of allogeneic transplant as a means of
      expediting hematopoietic recovery. Improved survival of UD transplant reaffirms
      its role as a valid therapeutic alternative in the absence of MSD.

PMID- 23551398
TI  - Structure-function relationship and biogenesis regulation of the human telomerase
      holoenzyme.
AB  - Telomeres are nucleoprotein structures found at the ends of linear chromosomes.
      Telomeric DNA shortens with each cell division, effectively restricting the
      proliferative capacity of human cells. Telomerase, a specialized reverse
      transcriptase, is responsible for de novo synthesis of telomeric DNA, and is the
      major physiological means by which mammalian cells extend telomere length.
      Telomerase activity in human soma is developmentally regulated according to cell
      type. Failure to tightly regulate telomerase has dire consequences: dysregulated
      telomerase activity is observed in more than 90% of human cancers, while haplo
      insufficient expression of telomerase components underlies several inherited
      premature aging syndromes. Over the past decade, we have significantly improved
      our understanding of the structure-activity relationships between the two core
      telomerase components: telomerase reverse transcriptase and telomerase RNA.
      Genetic screening for telomerase deficiency syndromes has identified new partners
      in the biogenesis of telomerase and its catalytic functions. These data revealed
      a level of regulation complexity that is unexpected when compared with the other
      cellular polymerases. In this review, we summarize current knowledge on the
      structure-activity relationships of telomerase reverse transcriptase and
      telomerase RNA, and discuss how the biogenesis of telomerase provides additional
      regulation of its actions.

PMID- 23551399
TI  - Segmental cherry angiomas associated with extragenital lichen sclerosus: a report
      of two cases.
AB  - Cherry angiomas (Campbell de Morgan spots) are common acquired red skin papules
      composed of dilated capillary loops, usually of unknown aetiology. Extragenital
      lichen sclerosus (LS) presents as porcelain-white scaly atrophic lesions with or
      without genital involvement. We report two cases of segmental multiple cherry
      angiomas in association with extragenital LS. Two unrelated women, aged 46 and 66
      years, presented with extragenital LS affecting their axillae and lower abdomen.
      During the examination, both patients were noted to have several hundred red skin
      papules in a segmental distribution, affecting the left thigh and flank of one
      woman, and the right abdomen and back of the other. Clinically and
      histologically, the papules were consistent with cherry angiomas. The striking
      segmental distribution of multiple cherry angiomas may be due to genetic
      mosaicism; however, segmental Fabry disease was excluded by sequence analysis of
      the alpha-galactosidase A gene. Any causal link between cherry angiomas and LS
      remains uncertain.

PMID- 23551400
TI  - Genome-wide association analysis of ten chilling tolerance indices at the
      germination and seedling stages in maize.
AB  - Maize seedlings are very sensitive to chilling, especially during the transition
      phase from heterotrophic to autotrophic growth. Genetic dissection of the genetic
      basis of chilling tolerance would provide useful information for genetic
      improvement of maize inbreds. In this study, genome-wide association analysis was
      conducted to explore the genetic architecture of maize chilling tolerance at the
      seed germination and seedling stages with an association panel of 125 inbreds.
      Ten tolerance indices (ratios of the performance of 10 germination rates and
      seedling growth-related traits under chilling stress and control conditions) were
      investigated to assess the ability of chilling tolerance of the inbreds, and a
      total of 43 single nucleotide polymorphisms associated with chilling tolerance
      were detected, with none of them being related to chilling tolerance at both the
      germination and seedling stages simultaneously. Correlation analysis also
      revealed that the genetic basis of chilling tolerance at the seed germination
      stage is generally different from that at the seedling stage. In addition, a
      total of 40 candidate genes involving 31 of the 43 single nucleotide
      polymorphisms were predicted, and were grouped into five categories according to
      their functions. The possible roles of these candidate genes in chilling
      tolerance were also discussed. 

PMID- 23551401
TI  - New insights into Chlamydomonas reinhardtii hydrogen production processes by
      combined microarray/RNA-seq transcriptomics.
AB  - Hydrogen production with Chlamydomonas reinhardtii induced by sulphur starvation
      is a multiphase process while the cell internal metabolism is completely
      remodelled. The first cellular response is characterized by induction of genes
      with regulatory functions, followed by a total remodelling of the metabolism to
      provide reduction equivalents for cellular processes. We were able to
      characterize all major processes that provide energy and reduction equivalents
      during hydrogen production. Furthermore, C. reinhardtii showed a strong
      transcript increase for gene models responsible for stress response and
      detoxification of oxygen radicals. Finally, we were able to determine potential
      bottlenecks and target genes for manipulation to increase hydrogen production or
      to prolong the hydrogen production phase. The investigation of transcriptomic
      changes during the time course of hydrogen production in C. reinhardtii with
      microarrays and RNA-seq revealed new insights into the regulation and remodelling
      of the cell internal metabolism. Both methods showed a good correlation. The
      microarray platform can be used as a reliable standard tool for routine gene
      expression analysis. RNA-seq additionally allowed a detailed time-dependent study
      of gene expression and determination of new genes involved in the hydrogen
      production process. 

PMID- 23551402
TI  - Melatonin protects against ischemic heart failure in rats.
AB  - Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an
      important role in heart failure. Melatonin is thought to have antiatherogenic,
      antioxidant, and vasodilatory effects. In this study, we investigated whether
      melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF
      was induced by left anterior descending (LAD) coronary artery ligation and rats
      were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end
      of this period, echocardiographic measurements were recorded and the rats were
      decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase,
      creatine kinase, aspartate aminotransferase, alanine aminotransferase, and
      lysosomal enzymes (beta-D-glucuronidase, beta-galactosidase, beta-D-N-acetyl
      glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma
      samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase
      3 and myeloperoxidase activities were determined in the cardiac samples.
      Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in
      cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin
      3 levels were also determined by histological analyses. In the vehicle-treated HF
      group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA
      activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and
      lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities
      were found to be increased. On the other hand, melatonin treatment reversed all
      the functional and biochemical changes. The present results demonstrate that Mel
      ameliorates ischemic heart failure in rats. These observations highlight that
      melatonin is a promising supplement for improving defense mechanisms in the heart
      against oxidative stress caused by heart failure. 

PMID- 23551403
TI  - The Bacillus subtilis mannose regulator, ManR, a DNA-binding protein regulated by
      HPr and its cognate PTS transporter ManP.
AB  - The transcriptional activator ManR of the Bacillus subtilis mannose utilization
      operon is composed of an N-terminal DNA-binding domain, two phosphotransferase
      system (PTS) regulation domains (PRDs), an EIIB(Bgl) - and an EIIA(Fru) -like
      domain. Site-specific mutagenesis of ManR revealed the role of conserved amino
      acids representing potential phosphorylation sites. This was investigated by beta
      galactosidase activity tests and by mobility shift assays after incubation with
      the PTS components HPr and EI. In analogy to other PRD-containing regulators we
      propose stimulation of ManR activity by phosphorylation. Mutations in PRD1
      lowered ManR activity, whereas mutations in PRD2 abolished ManR activity
      completely. The Cys415Ala (EIIB(Bgl)) and the His570Ala mutations (EIIA(Fru))
      provoked constitutive activities to different degrees, whereas the latter had the
      greater influence. Addition of EIIBA(Man) reduced the binding capability
      significantly in a wild-type and a Cys415Ala background, but had no effect on a
      His570Ala mutant. The different expression levels originating from the two
      promoters PmanR and PmanP could be ascribed to different 5'-untranslated mRNA
      regions. Sequences of 44 bp were identified and confirmed as the ManR binding
      sites by DNase I footprinting. The binding properties of ManR, in particular the
      equilibrium dissociation constant KD and the dissociation rate kdiss, were
      determined for both promoter regions.

PMID- 23551404
TI  - Subthalamic deep brain stimulation with a new device in Parkinson's disease: an
      open-label trial.
AB  - OBJECTIVE: We aimed to evaluate the safety and efficacy of subthalamic nucleus
      deep brain stimulation (STN-DBS) with a new stimulator (Beijing PINS Medical Co.,
      Ltd, PNS 1101) in Parkinson's disease (PD). MATERIALS AND METHODS: Forty patients
      received a PINS device implantation in the subthalamic nucleus. The effects of
      stimulation on motor score, activities of daily living, good-quality on-time, and
      the levodopa-equivalent dose were analyzed for all 40 patients with PD treated
      with bilateral or unilateral STN-DBS. The scores were collected at baseline in
      two conditions (on/off medication) and at 3, 6, 9, 12, and 24 months of follow-up
      with stimulation in the absence or presence of medication. The patients were
      followed up for two years. RESULTS: At 3, 6, 9, 12, and 24 months of follow-up,
      our results showed a significant increase from baseline in both activities of
      daily living and motor scores (p < 0.001) and good-quality on-time (p < 0.001);
      the daily levodopa-equivalent dose decreased compared with baseline (p < 0.01).
      No patient died during the study, and none of the adverse effects were classified
      as severe. All of the adverse events were resolved or improved by the end of the
      study. CONCLUSIONS: STN-DBS with the PINS device significantly improved the
      symptoms of PD when compared with baseline in this trial. This new device may be
      recommended for the treatment of patients with advanced PD; however, a
      randomized, double-blinding trial will be required.

PMID- 23551405
TI  - Rivastigmine patch for treatment of Alzheimer's disease in clinical practice in
      Thailand.
AB  - BACKGROUND: Rivastigmine is a cholinesterase inhibitor for treatment of mild to
      moderate Alzheimer's disease (AD) and dementia associated with Parkinson's
      disease. The new patch formulation was recently made available. We assessed the
      safety, tolerability, and cognitive outcome of rivastigmine patch in treatment of
      mild to moderate AD in clinical practice in Thailand. METHODS: A multicentre,
      hospital-based, prospective observational study was conducted in nine hospitals
      across Thailand. Patients with probable mild to moderate AD who received the
      rivastigmine patch were enrolled. Data were collected data at baseline, weeks 4-8
      and after week16. RESULTS: A total of 116 AD patients were screened, and three
      were excluded. Of 113 patients, 62.8% were women with a mean age of 73.3 +/- 9.2
      years; 79.7% were newly diagnosed. One-third of all patients had been using
      antipsychotic or antidepressant medication. Common comorbidities were
      hypertension and dyslipidemia. The Thai Mental State Examination score
      significantly increased from 18.6 to 20.3 (weeks 4-8) and 20.4 (week 16+) (P <
      0.001). Scores based on physicians' (Clinical Global Impression) and caregivers'
      (Patients' Caregiver Global Impression of Change) impressions of improvement
      suggested minimal improvement. Because of adverse events, seven patients's
      dosages were reduced 10 cm(2) to 5 cm(2) or from 5 cm(2) to nothing. Itching was
      the most common adverse symptom. CONCLUSIONS: During the first 16 weeks after
      initiation of rivastigmine patch therapy, patients with probable mild to moderate
      AD had statistically significant improvement in cognitive function, but
      clinically marginal benefit. Rivastigmine was safe and well tolerated.

PMID- 23551407
TI  - Expert-based drug lists to measure anticholinergic burden: similar names,
      different results.
AB  - BACKGROUND: Scoring scales such as the Anticholinergic Drug Scale (ADS), the
      Anticholinergic Risk Scale (ARS), and the Anticholinergic Cognitive Burden Scale
      (ACB) provide an estimation of total anticholinergic burden. Not all the lists
      include the same drugs, and the points given for certain drugs differ among them.
      Whether these discrepancies present important differences in the estimation of
      anticholinergic burden for an individual patient is unknown. Therefore, the aim
      of this study is to assess agreement among the three scales. METHOD:
      Anticholinergic burden was measured with the three scales in 83 patients aged
      >=65 years in a medium- and long-stay psychiatric hospital. Subsequently,
      patients were categorized into three risk categories: low risk (0 points), medium
      risk (1-2 points) or high risk (3 or more points). The chance-corrected measures
      of agreement for the different scores were determined with the k-statistic
      (kappa). RESULTS: Values for kappa were: 0.19 for Anticholinergic Risk Scale
      Anticholinergic Drug Scale, 0.21 for ACB-Anticholinergic Drug Scale and 0.25 for
      Anticholinergic Risk Scale-ACB. The mean anticholinergic burden measured with ACB
      was 3.28. CONCLUSIONS: There is poor agreement among the three scales. These
      lists cannot be directly applied to different settings in which drug availability
      differs substantially, and they require periodic updates. Anticholinergic burden
      in our setting (psychogeriatric inpatients) was particularly high.

PMID- 23551406
TI  - Intelligence or years of education: which is better correlated with memory
      function in normal elderly Japanese subjects?
AB  - BACKGROUND: We compared differences in intelligence and memory function between
      normal elderly Japanese subjects with more years of education and those with
      fewer years of education. We also investigated clinical and neuropsychological
      factors that are strongly correlated with memory function. METHODS: There were
      118 normal elderly subjects who underwent the Mini-Mental State Examination,
      Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III), and Wechsler Memory
      Scale Revised. Subjects with at least 13 years of education were categorized as
      the H group, and those with 12 years of education or less were categorized as the
      L group. RESULTS: Age and Mini-Mental State Examination scores were not
      significantly different between the two groups. On the WAIS-III, there were
      significant differences between the two groups in Verbal IQ and Full Scale IQ. On
      the Wechsler Memory Scale Revised, there were significant differences between the
      two groups in Visual Memory, General Memory, and Delayed Recall. Correlation
      coefficients between memory function and the other factors demonstrated
      significant but weak correlations between years of education and General Memory
      (R = 0.22) and between years of education and Delayed Recall (R = 0.20). Strong
      correlations were found between Verbal IQ and Verbal Memory (R = 0.45), between
      Verbal IQ and General Memory (R = 0.49), between Full Scale IQ and General Memory
      (R = 0.50) and between Full Scale IQ and Delayed Recall (R = 0.48). CONCLUSIONS:
      In normal elderly Japanese subjects, years of education weakly correlated with
      memory function while Verbal IQ, Full Scale IQ and Verbal Comprehension on WAIS
      III had stronger correlations with memory function. Verbal IQ and Verbal
      Comprehension on WAIS-III were found to be insusceptible to the cognitive decline
      characteristic of Alzheimer's disease or amnestic mild cognitive impairment.
      Therefore, verbal intelligence, as measured by Verbal IQ and Verbal
      Comprehension, may be the most useful factor for inferring premorbid memory
      function in Alzheimer's disease or amnestic mild cognitive impairment patients.

PMID- 23551408
TI  - Using hypernatraemic events to predict reduced renal function in elderly lithium
      patients: a brief report.
AB  - BACKGROUND: Diabetes insipidus (DI) is a recognized adverse effect of lithium
      use, and studies have shown an association between decreased renal function and
      DI in patients using lithium. We hypothesize that hypernatraemic events that
      occur in DI predict decreased renal function in elderly patients on lithium.
      METHODS: We conducted a retrospective cohort study involving 55 geriatric
      psychiatry patients using lithium between 1985 and 2010. Patients who always had
      sodium levels <=146 mmol/L were compared to patients with one or more episodes of
      hypernatraemia (serum sodium level >=147 mmol/L) for estimated glomerular
      filtration rate (eGFR) levels and prevalence of severe chronic renal failure
      (eGFR <=30 mL/min/1.73 m(2)). RESULTS: eGFR was found to be less in the
      hypernatraemic group than in the non-hypernatraemic controls (41 vs 56
      mL/min/1.73 m(2); P = 0.0074). Severe chronic renal failure appeared more
      prevalent in hypernatraemic patients (4/14 (28.6%) vs. 3/41 (7.3%)), but this did
      not achieve statistical significance (P = 0.061). The two groups did not differ
      for age, sex, medical comorbidities or other clinical variables, except
      antidepressant use. Hypernatraemic patients appeared less likely to use
      antidepressants than non-hypernatraemic patients, odds ratio = 0.69 (P = 0.020).
      However, in multivariate analysis, hypernatraemia correlated with decreased eGFR
      (beta = -0.39, P = 0.004), while antidepressant use did not (P = 0.81).
      CONCLUSIONS: These results suggest that hypernatraemic events may predict reduced
      renal function in geriatric patients using lithium. The role of hypernatraemia
      and DI in renal failure in this population requires further study. Health
      professionals should be aware of the risks of renal failure in older patients
      treated with lithium, especially in the context of sodium level abnormalities.

PMID- 23551409
TI  - Effects of Yangxue Qingnao Granules on chronic cerebral circulation
      insufficiency: a randomized, double-blind, double-dummy, controlled multicentre
      trial.
AB  - BACKGROUND: There is a great deal of interest in traditional Chinese medicine as
      a treatment for chronic cerebral circulation insufficiency (CCCI). In the present
      study, we evaluated the efficacy and safety of Yangxue Qingnao Granules (YXQNG)
      as a monotherapy in patients with CCCI. METHODS: From July 2007 to May 2010, 273
      patients with CCCI at nine centres in China were randomly assigned to receive
      either YXQNG with nimodipine placebo (n= 140, 12 g/day) or nimodipine with YXQNG
      placebo (n= 133, 30 mg/day) for 8 weeks. The primary end points after 8 weeks of
      treatment were changes from baseline in severity of headache, heavy-headed
      feeling, dizziness and sleep disorder. RESULTS: The mean baseline levels of
      headache, heavy-headed feeling, dizziness and sleep disorder were comparable
      between the two groups. Both therapies significantly improved these symptoms
      after 8 weeks of treatment (P < 0.001). Compared with nimodipine therapy, YXQNG
      resulted in similar reductions in these symptoms. No adverse effects were
      observed in the YXQNG group. CONCLUSIONS: These data demonstrate that YXQNG as a
      monotherapy were as effective as nimodipine monotherapy in improving the symptoms
      of CCCI. It is well-tolerated and may have an important place in the management
      of this condition. Whether a combination of these two medicines will increase
      therapeutic efficacy deserves further clinical investigation.

PMID- 23551410
TI  - Reduced memory in fat mass and obesity-associated allele carriers among older
      adults with cardiovascular disease.
AB  - BACKGROUND: Much attention has been paid to the prevalence and predisposition of
      the fat mass and obesity-associated (FTO) gene to obesity, although only a few
      studies have characterized the extent to which this affects cognitive function.
      This study examined differences between risk allele carriers (i.e. FTO-AC/AA) and
      non-carriers (i.e. FTO-CC) on indices of attention/executive function/psychomotor
      speed, memory, language, and visual-spatial ability in a sample of older patients
      with cardiovascular disease. METHODS: We recruited 120 older adults from an
      outpatient cardiology clinic who underwent blood draw and completed
      neuropsychological testing. Participants were classified into two groups: one for
      those who were homozygous for the non-risk-conferring allele (i.e. FTO-CC) (n=
      49) and the other for those who had at least one copy of the obesity risk
      conferring A allele (i.e. FTO-AC/AA) (n= 71). RESULTS: Mancova analyses adjusting
      for age and years of education revealed the FTO-AC/AA group performed
      significantly worse on indices of memory (lambda= 0.94, F(2, 115) = 3.58, P=
      0.03, partial eta(2) = 0.06). Follow-up tests revealed a significant effect for
      the FTO-AC/AA group, relative to the non-carrier group, on encoding (i.e.
      California Verbal Learning Test Total Learning) and California Verbal Learning
      Test long-delay free recall (P < 0.05). No such differences between FTO carriers
      and non-carriers emerged on tests of attention/executive function/psychomotor
      speed, language, or visual-spatial ability (P > 0.05 for all). CONCLUSIONS: These
      findings suggest that the FTO risk allele is associated with reduced memory
      performance, particularly on aspects of memory encoding and delayed recall. To
      elucidate underlying mechanisms, these findings will need to be replicated in
      larger samples that utilize neuroimaging.

PMID- 23551411
TI  - Reversibility of brain morphology after shunt operations and preoperative
      clinical symptoms in patients with idiopathic normal pressure hydrocephalus.
AB  - AIM: Brain deformations might prevent clinical symptoms from worsening in
      patients with idiopathic normal pressure hydrocephalus (iNPH). We investigated
      the relationship between reversibility of brain morphology after shunt operations
      and preoperative clinical symptoms in iNPH patients. METHODS: Using head magnetic
      resonance images with voxel-based morphometry, we measured the cerebrospinal
      fluid volume in the combined areas of the lateral and third ventricles and
      Sylvian fissure (the volume of the ventricles and Sylvian fissure (vVS)) and the
      volume of the subarachnoid space at high convexity and midline areas (vHCM)
      before and 1 year after lumboperitoneal shunt operations in 12 patients with
      shunt-responsive iNPH. We used the ratio of normalized vVS to normalized vHCM
      (nvVS/nvHCM) as an index of the severity of the brain deformation. The degree of
      reversibility of the brain morphology after the shunt operation was defined as
      the change ratio of the preoperative nvVS/nvHCM to the postoperative nvVS/nvHCM
      (CR-nvVS/nvHCM). Higher CR-nvVS/nvHCM values indicated more improvement in the
      brain deformation. In addition, we rated the severity of the white matter lesions
      on the preoperative magnetic resonance images based on the Fazekas scale.
      Dependency in activities of daily living, gait and cognition were evaluated
      before and 1 year after the shunt operations. RESULTS: After the shunt
      operations, the nvVS/nvHCM and nvVS decreased significantly, and nvHCM increased
      significantly. The CR-nvVS/nvHCM negatively correlated with the preoperative
      severity of dependency in activities of daily living, gait and cognitive
      impairments. The CR-nvVS/nvHCM negatively correlated with the Fazekas scale, but
      not with age, duration of the disease and cerebrospinal fluid pressure.
      CONCLUSIONS: Reversibility of brain morphology, which varied among iNPH patients,
      would prevent clinical symptoms from worsening in iNPH patients. The presence of
      white matter lesions reduced the degree of reversibility of the brain
      deformations in iNPH patients.

PMID- 23551412
TI  - Thyrotoxic psychosis in an elderly woman and haloperidol use: a case report.
AB  - Thyrotoxic patients may occasionally present with affective disorders. Here, we
      discuss a case of a 61-year-old woman with misidentification and persecutory
      delusions, olfactory hallucinations, and apathy associated with thyrotoxicosis.
      After definitive antithyroid and antipsychotic agent haloperidol treatments, the
      patient was released within 4 weeks. Thyrotoxic psychosis with apathy is a rare
      entity that can be misdiagnosed as affective psychosis. Haloperidol may be an
      alternative treatment in resolving psychotic features beside the treatment of
      hyperthyroid state.

PMID- 23551413
TI  - Cognitive effects of quetiapine in a patient with dementia with Lewy bodies.
AB  - A recent large-scale randomized controlled clinical trial, the Clinical
      Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study,
      found a significant worsening of cognitive functioning in a sample of patients
      with Alzheimer's disease. To date there have been no equally powered studies
      examining the cognitive effects of atypical antipsychotics in patients with
      dementia with Lewy bodies, the second most prevalent neurodegenerative disorder.
      This case report describes a significant cognitive improvement observed through
      the use of an atypical antipsychotic in a patient with dementia with Lewy bodies.
      The observed divergence in cognitive responsiveness is discussed mechanistically
      on both the clinical and neuromolecular level. Limitations to this case study
      design are presented and discussed. The prudence of caution in importing the
      results of the Clinical Antipsychotic Trials of Intervention Effectiveness
      Alzheimer's Disease study to the dementia with Lewy bodies population is
      summarized and presented for psychiatrists, neurologists and primary care
      providers, with an intent to stimulate discussion and further research.

PMID- 23551414
TI  - Managing abnormal eating behaviours in frontotemporal lobar degeneration patients
      with topiramate.
AB  - Abnormal eating behaviours are specific to frontotemporal lobar degeneration and
      increase caregiver burden. Topiramate, an anticonvulsant, suppresses cravings for
      alcohol and other substances and is a potential treatment for binge eating.
      However, there are few reports on topiramate efficacy for abnormal eating
      behaviours in frontotemporal lobar degeneration patients. We present three
      Japanese frontotemporal lobar degeneration patients with abnormal eating
      behaviours. Topiramate was effective, especially for compulsive eating, in cases
      with distinct lobar atrophy, but not for all abnormal eating behaviours.

PMID- 23551415
TI  - A literature review of case formulation to inform mental health practice.
AB  - Changes in mental health provision have led to practitioners and service
      providers reviewing how they incorporate service users in assessment processes
      and treatment decisions. Case formulation (CF) is a framework that informs a
      choice of psychological treatments providing a bridge between assessment and
      treatment phases to guide treatment options. However, CF is not routinely
      practised in mental health; hence this paper reviews CF literature to establish
      its efficacy for service users experiencing mental health issues. The purpose of
      this study is to assess the efficacy, reliability and validity of CF and its
      process and function in providing treatment for service users experiencing mental
      health issues and to explore practitioner training requirements. A systematic
      search of English language publications on CF and treatment frameworks from 1999
      2011 was conducted searching electronic databases. Additionally, two seminal
      pieces of CF work were included. The findings demonstrate evidence of CF's
      efficacy and suggest practitioner training programmes to increase professional
      expertise and enhance service user outcomes. However, limited evidence exists and
      further research is required to address efficacy and training implications of CF.

PMID- 23551416
TI  - Cardiovascular magnetic resonance demonstrates reversible atrial dysfunction
      after catheter ablation of persistent atrial fibrillation.
AB  - INTRODUCTION: There is a paucity of data on atrial injury following ablation of
      persistent atrial fibrillation (AF). This study aimed at assessing reversibility
      of atrial dysfunction after successful persistent AF ablation using
      cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: CMR was performed
      during sinus rhythm (SR) in 20 consecutive patients with persistent AF at
      baseline (BL) within 24 hours after ablation and after 6-month follow-up (FU).
      Catheter ablation included atrial substrate modification using the stepwise
      approach following pulmonary vein isolation (PVI) in order to attempt termination
      of persistent AF. Active left (LA) and right atrial (RA) function were quantified
      by calculating the active emptying fraction (AEF) from transvalvular flow
      profiles using velocity encoded (VENC) CMR. LA appendage (LAA) function was
      quantified by measurements of peak a-wave velocities from flow profiles
      perpendicular to the LAA orifice. Peri-atrial edema was assessed using black
      blood T2 -weighted CMR. A significant improvement was found in LA-AEF from 18 (12
      26)% at BL to 25 (22-35)% at FU (P = 0.0001). Furthermore, RA-AEF significantly
      increased from 31 (19-35)% at BL to 40 (35-51)% at FU (P < 0.0001). A significant
      improvement was also found for LAA a-wave velocities from 45 (31-65) cm/s at BL
      to 62 (49-75) cm/s at FU (P < 0.01). The area of peri-atrial edema on T2 
      weighted CMR decreased from 1393 (1098-1797) mm(2) at BL to 24 (1-92) mm(2) at FU
      (P < 0.0001). CONCLUSION: CMR demonstrates reversibility of LA, LAA, and RA
      dysfunction associated with resorption of peri-atrial edema in patients with SR
      after persistent AF ablation.

PMID- 23551417
TI  - Approximate Bayesian estimation of extinction rate in the Finnish Daphnia magna
      metapopulation.
AB  - Approximate Bayesian computation (ABC) is useful for parameterizing complex
      models in population genetics. In this study, ABC was applied to simultaneously
      estimate parameter values for a model of metapopulation coalescence and test two
      alternatives to a strict metapopulation model in the well-studied network of
      Daphnia magna populations in Finland. The models shared four free parameters: the
      subpopulation genetic diversity (thetaS), the rate of gene flow among patches
      (4Nm), the founding population size (N0) and the metapopulation extinction rate
      (e) but differed in the distribution of extinction rates across habitat patches
      in the system. The three models had either a constant extinction rate in all
      populations (strict metapopulation), one population that was protected from local
      extinction (i.e. a persistent source), or habitat-specific extinction rates drawn
      from a distribution with specified mean and variance. Our model selection
      analysis favoured the model including a persistent source population over the two
      alternative models. Of the closest 750,000 data sets in Euclidean space, 78% were
      simulated under the persistent source model (estimated posterior probability =
      0.769). This fraction increased to more than 85% when only the closest 150,000
      data sets were considered (estimated posterior probability = 0.774). Approximate
      Bayesian computation was then used to estimate parameter values that might
      produce the observed set of summary statistics. Our analysis provided posterior
      distributions for e that included the point estimate obtained from previous data
      from the Finnish D. magna metapopulation. Our results support the use of ABC and
      population genetic data for testing the strict metapopulation model and
      parameterizing complex models of demography.

PMID- 23551418
TI  - MUC5AC and inflammatory mediators associated with respiratory outcomes in the
      British 1946 birth cohort.
AB  - BACKGROUND AND OBJECTIVE: Dysregulation of respiratory mucins, MUC5AC in
      particular, has been implicated in respiratory disease and MUC5AC expression is
      up-regulated in response to environmental challenges and inflammatory mediators.
      The aim of this study was to examine the effect of genetic variation on
      susceptibility to common respiratory conditions. METHODS: The association of
      MUC5AC and the closely linked genes MUC2 and MUC5B with respiratory outcomes was
      tested in the MRC National Survey of Health and Development, a longitudinal birth
      cohort of men and women born in 1946. Also examined were the functional variants
      of the genes encoding inflammatory mediators, IL13, IL1B, IL1RN, TNFA and ERBB1,
      for which there is a likely influence on MUC5AC expression and were explored
      potential gene-gene interactions with these inflammatory mediators. RESULTS:
      Statistically significant associations between the 3'ter MUC5AC simple nucleotide
      polymorphism (SNP) rs1132440 and various non-independent respiratory outcomes
      (bronchitis, wheeze, asthma, hay fever) were reported while the adjacent loci
      show slight (but largely non-statistically significant) differences, presumably
      reflective of linkage disequilibrium (allelic association) across the region. A
      novel association between bronchitis and a non-synonymous functional ERBB1 SNP,
      rs2227983 (aka epidermal growth factor receptor:R497K, R521K) is also reported
      and evidence presented of interaction between MUC5AC and ERBB1 and between MUC5AC
      and IL1RN with respect to bronchitis. The ERBB1 result suggests a clear mechanism
      for a biological interaction in which the allelic variants of epidermal growth
      factor receptor differentially affect mucin expression. CONCLUSIONS: The MUC5AC
      association and the interactions with inflammatory mediators suggest that
      genetically determined differences in MUC5AC expression alter susceptibility to
      respiratory disease.

PMID- 23551420
TI  - Antiangiogenic factors and maternal hemodynamics during intensive hemodialysis in
      pregnancy.
AB  - We report on a 21-year-old pregnant patient with IgA nephropathy who was
      initiated on intensive hemodialysis (8 hours of hemodialysis 3 times a week) at a
      gestational age of 26 weeks on the basis of worsening kidney function resulting
      in rapidly progressive fatigue and difficulties in metabolic control. Throughout
      the pregnancy, and while on intensive hemodialysis, 24-hour ambulatory blood
      pressure control was within the target, and results of weekly 24-hour measurement
      of central hemodynamics and pulse wave velocity, and of serial levels of
      circulating (anti-)angiogenic factors were comparable to normal pregnancies.
      Estimated fetal growth evolved along the 50th percentile, and no polyhydramnios
      was detected. After induction for a sudden, unexplained increase in blood
      pressure, she delivered a healthy boy of 2480 g at a gestational age of 36 weeks.
      This case adds to the expanding literature that supports the use of intensive
      hemodialysis in pregnant patients with end-stage renal disease and illustrates,
      for the first time, the potential use of serial (anti-) angiogenic factors and 24
      hour measurements of blood pressure and hemodynamic indices in order to
      facilitate monitoring of these complicated patients.

PMID- 23551419
TI  - Wound biofilms: lessons learned from oral biofilms.
AB  - Biofilms play an important role in the development and pathogenesis of many
      chronic infections. Oral biofilms, more commonly known as dental plaque, are a
      primary cause of oral diseases including caries, gingivitis, and periodontitis.
      Oral biofilms are commonly studied as model biofilm systems as they are easily
      accessible; thus, biofilm research in oral diseases is advanced with details of
      biofilm formation and bacterial interactions being well elucidated. In contrast,
      wound research has relatively recently directed attention to the role biofilms
      have in chronic wounds. This review discusses the biofilms in periodontal disease
      and chronic wounds with comparisons focusing on biofilm detection, biofilm
      formation, the immune response to biofilms, bacterial interaction, and quorum
      sensing. Current treatment modalities used by both fields and future therapies
      are also discussed.

PMID- 23551421
TI  - The inhibitor of wax 1 locus (Iw1) prevents formation of beta- and OH-beta
      diketones in wheat cuticular waxes and maps to a sub-cM interval on chromosome
      arm 2BS.
AB  - Glaucousness is described as the scattering effect of visible light from wax
      deposited on the cuticle of plant aerial organs. In wheat, two dominant genes
      lead to non-glaucous phenotypes: Inhibitor of wax 1 (Iw1) and Iw2. The molecular
      mechanisms and the exact extent (beyond visual assessment) by which these genes
      affect the composition and quantity of cuticular wax is unclear. To describe the
      Iw1 locus we used a genetic approach with detailed biochemical characterization
      of wax compounds. Using synteny and a large number of F2 gametes, Iw1 was fine
      mapped to a sub-cM genetic interval on wheat chromosome arm 2BS, which includes a
      single collinear gene from the corresponding Brachypodium and rice physical maps.
      The major components of flag leaf and peduncle cuticular waxes included primary
      alcohols, beta-diketones and n-alkanes. Small amounts of C19-C27 alkyl and
      methylalkylresorcinols that have not previously been described in wheat waxes
      were identified. Using six pairs of BC2 F3 near-isogenic lines, we show that Iw1
      inhibits the formation of beta- and hydroxy-beta-diketones in the peduncle and
      flag leaf blade cuticles. This inhibitory effect is independent of genetic
      background or tissue, and is accompanied by minor but consistent increases in n
      alkanes and C24 primary alcohols. No differences were found in cuticle thickness
      and carbon isotope discrimination in near-isogenic lines differing at Iw1.

PMID- 23551425
TI  - The modulation of visual and task characteristics of a writing system on
      hemispheric lateralization in visual word recognition-a computational
      exploration.
AB  - Through computational modeling, here we examine whether visual and task
      characteristics of writing systems alone can account for lateralization
      differences in visual word recognition between different languages without
      assuming influence from left hemisphere (LH) lateralized language processes. We
      apply a hemispheric processing model of face recognition to visual word
      recognition; the model implements a theory of hemispheric asymmetry in perception
      that posits low spatial frequency biases in the right hemisphere and high spatial
      frequency (HSF) biases in the LH. We show two factors that can influence
      lateralization: (a) Visual similarity among words: The more similar the words in
      the lexicon look visually, the more HSF/LH processing is required to distinguish
      them, and (b) Requirement to decompose words into graphemes for grapheme-phoneme
      mapping: Alphabetic reading (involving grapheme-phoneme conversion) requires more
      HSF/LH processing than logographic reading (no grapheme-phoneme mapping). These
      factors may explain the difference in lateralization between English and Chinese
      orthographic processing. 

PMID- 23551426
TI  - Age-gender differences in the reaction times of ankle muscles.
AB  - AIM: Reaction times of the hip abductor were reported to be longer in elderly
      women than in elderly men, and this was suggested to be related to mediolateral
      balance performance. The aim of the present study was to investigate the effects
      of age and gender on the reaction performance of ankle muscles, which have
      predominant roles in anterioposterior balance control. METHODS: A total of 40
      elderly subjects and 40 young subjects (even number of men and women) carried out
      a series of isometric plantarflexions and dorsiflexions, as forcefully and
      quickly as possible, in response to auditory stimulus. Surface electromyogram at
      the dorsiflexor and plantarflexor were recorded, together with foot plantar
      force. Premotor time, motor time and total reaction time derived from the
      experimental data were compared between age groups and genders by two-way anova.
      RESULTS: Both dorsiflexor and plantarflexor showed similar reaction performance.
      Premotor time increased with age with no gender difference. Motor time increased
      with age in women and not in men, resulting in longer motor time in elderly women
      than in elderly men. Total reaction time was dominated by premotor time, so that
      it was longer in the elderly with no gender difference. CONCLUSION: Although age
      related elongation of motor time was greater in women, total reaction time was
      not different between the genders. This may be related to no gender difference in
      anterioposterior balance performance.

PMID- 23551427
TI  - Histological, radiological and histomorphometric evaluation of immediate vs. non
      immediate loading of a zirconia implant with surface treatment in a dog model.
AB  - OBJECTIVE: The aim of this study was to assess the performance of zirconia
      implants under immediate loading compared with delayed loading in dogs over 30-90
      days. MATERIALS AND METHODS: Tooth extractions were made for the subsequent
      placement of dental implants at premolars P2, P3, P4 and molars M1 bilaterally in
      the dog mandible. Forty eight zirconia implants, 4 mm in diameter and 10 mm in
      length, were inserted, whose neck and body surfaces had been treated with
      femtosecond laser texturing; 24 implants were loaded immediately and 24 remained
      unloaded during the osseointegration period. Final radiographs were taken
      recording stability values before sacrifice at 30 or 90 days when sample removal
      for histological and histomorphometric analysis was performed. Bone-to-implant
      contact, crestal bone loss and implant stability were evaluated at these two
      study times. RESULTS: Bone-to-implant contact values after 30 days were 38.9% for
      immediately loaded implants and 32% for non-loaded implants. After 90 days,
      values increased to 65% for immediately loaded and 57.6% for non-loaded implants.
      After 30 days, there was more crestal bone lost in the non-loaded group (0.58 +/-
      0.28 mm) compared with the immediately loaded group (0.5 +/- 0.3 mm). After 90
      days, there was improved stability in both groups, but was lower in the
      immediately loaded group (0.5 +/- 0.23 mm) compared with the non-loaded group
      (0.56 +/- 0.28 mm). Initial implant stability values were -3.5 PTV at the moment
      of implant placement. Stability values after the first 30 days were -4 for
      immediately loaded implants and -3 for non-loaded. At 90 days, non-loaded
      implants showed -4.9, whereas immediately loaded showed -7.1. CONCLUSIONS: For
      the different parameters studied, zirconia implants treated with femtosecond
      laser and subjected to immediate loading showed better results compared with non
      loaded implants in terms of BIC, crestal bone loss and implant stability.

PMID- 23551428
TI  - Novel MBTPS2 missense mutation in the N-terminus transmembrane domain in a
      patient with ichthyosis follicularis, alopecia, and photophobia syndrome.
AB  - Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome is an X-linked
      dominant condition characterized by the triad of ichthyosis follicularis,
      alopecia, and photophobia caused by mutations in the MBTPS2 gene. Herein we
      describe a proband with IFAP syndrome with mild cutaneous manifestations and a
      novel MBTPS2 mutation in the N-terminal transmembrane domain. 

PMID- 23551429
TI  - Clinical significance of vascular endothelial growth factor and vascular
      endothelial growth factor receptor-2 gene polymorphisms in patients with
      gastrointestinal stromal tumors.
AB  - AIM: The vascular endothelial growth factor (VEGF) or its family might play role
      in tumor-related angiogenesis in gastrointestinal stromal tumors (GIST), thereby
      affecting the prognosis. Accordingly, the present study analyzed the impact of
      VEGF and VEGF receptor-2 (VEGFR-2) gene polymorphisms on the prognosis for GIST
      patients. METHODS: In all, 213 consecutive patients with GIST from five medical
      centers were enrolled in the present study. The genomic DNA was extracted from
      paraffin-embedded tumor tissue, and four VEGF (-2578C/A, -1498C/T, -634G/C, and
      +936C/T) and one VEGFR-2 (+1416A/T) gene polymorphisms were determined using a
      Sequenom MassARRAY system. RESULTS: With a median follow up of 18.4 months, the
      estimated 5-year relapse-free survival and overall survival rates were 70 and
      87%, respectively. In a multivariate analysis including age, sex, primary site of
      disease, pathology and risk stratification, no significant association was
      observed between the polymorphism of the VEGF and VEGFR-2 genes and survival.
      CONCLUSION: None of the five VEGF and VEGFR-2 gene polymorphisms investigated in
      this study was found to be an independent prognostic marker for Korean patients
      with surgically resected GIST. However, further studies on a larger scale are
      warranted to clarify the role of VEGF and VEGFR gene polymorphisms as a
      prognostic biomarker for GIST patients.

PMID- 23551431
TI  - Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli.
AB  - OBJECTIVE: To determine the hedgehog (Hh) signaling pathway correlated with the
      development of colon cancer and melanosis coli. METHODS: Protein and mRNA levels
      of Hh signaling pathway components (sonic hedgehog [Shh], protein patched homolog
      1 [Ptch 1], GLI family zinc finger 1 [Gli 1] and suppressor of fused homolog
      [Drosophila] [Sufu]) in 127 patients with colon cancer, 36 with melanosis coli
      and 20 adjacent normal mucosal tissues taken from surgical specimens were
      evaluated using antibody staining and quantitative real-time polymerase chain
      reaction. RESULTS: In adjacent normal tissue Shh and Ptch1, but not Gli1 or Sufu,
      were weakly expressed and mainly in the lining epithelium of the colonic mucosa.
      In cancerous tissues Shh and Gli1 were uniformly strong while Ptch1 was patchy
      and weak, and Sufu uniformly weak, which paralleled their levels of corresponding
      mRNA. Elevated protein levels of Shh and Ptch were significantly associated with
      mucinous colonic tissues. Elevated Sufu protein levels were positively correlated
      with the diameter and invasion of the tumor. In patients with melanosis coli,
      mRNA levels of Shh, Ptch1, Gli1 and Sufu were very low, which was similar to
      those of adjacent normal tissues; but protein levels of Shh, Ptch1 and Gli1, but
      not Sufu, were high, which was similar to those of cancerous tissues.
      CONCLUSIONS: The mRNA and protein levels of Hh pathway components are aberrantly
      elevated in colon cancer, which may be the potential molecular classification
      markers. Further studies are required to determine the role of melanosis coli in
      the colon tumorigenesis.

PMID- 23551430
TI  - Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 RSK2.
AB  - Multiple lines of evidence suggest that natural compounds can prevent skin ageing
      induced by ultraviolet light. Luteolin, a bioactive compound found in chilli,
      onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing
      effects in vitro. However, the molecular targets and mechanisms of luteolin are
      still poorly understood. In this study, we sought to investigate the effects of
      luteolin on UVB-induced photoageing and the molecular mechanisms involved, using
      HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit
      UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of
      AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as
      well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western
      blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not
      inhibited by luteolin. In vitro kinase assay data revealed that luteolin
      significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2.
      Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and
      p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle
      formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin,
      in vivo. Taken together, our observations suggest that luteolin exhibits anti
      photoageing effects in vitro and in vivo and may have potential as a treatment
      for the prevention of skin ageing.

PMID- 23551432
TI  - Pain characteristics and self-rated health after elective orthopaedic surgery - a
      cross-sectional survey.
AB  - AIMS AND OBJECTIVES: To describe the postoperative pain and to examine the
      relationship between pain intensity, pain interference and self-rated health
      after elective orthopaedic surgery. BACKGROUND: Pain is a problem for many
      surgical inpatients and can lead to postoperative complications. Limited
      knowledge exists about the relationship between postoperative pain, function and
      self-rated health. DESIGN: Cross-sectional survey. METHODS: Pain characteristics,
      self-rated health, sociodemographic status and comorbidity were measured in 123
      elective orthopaedic inpatients recruited consecutively from a hospital in
      eastern Norway in 2012. On the day they were discharged from the surgical unit,
      patients completed items about pain intensity and pain interference from the
      Brief Pain Inventory and about self-rated health from the Medical Outcome Short
      Form-36 Health Survey. Clinical data were retrieved from the medical records.
      Patients were divided into three diagnostic groups: shoulder surgery, hip or knee
      replacement and other surgery. RESULTS: Mean age was 60 years (SD 17.2) and 50%
      were females. Average pain intensity was 4.2 (SD 2.2) on a 0-10 numeric rating
      scale and 60% reported moderate/severe pain during the entire hospital stay.
      Shoulder surgery patients reported significantly higher pain intensity compared
      to other surgical groups. Pain interfered mostly with daily activity and sleep.
      Higher pain intensity was significantly associated with poorer self-rated health.
      The linear regression analysis showed that average pain intensity was related to
      poorer self-rated health, controlling for sociodemographic variables and pain
      interference with function. CONCLUSION: High pain intensity is related to poorer
      self-rated health. Postoperative pain is undermanaged, affects functional areas
      and could delay rehabilitation. RELEVANCE TO CLINICAL PRACTICE: Postoperative
      pain management should be given high priority after elective orthopaedic surgery,
      in order to improve self-rated health and function. Pain treatment for shoulder
      surgery patients may require more attention than it currently receives.

PMID- 23551433
TI  - Techniques to increase lymph node harvest from gastrointestinal cancer specimens:
      a systematic review and meta-analysis.
AB  - AIMS: This review aims to compare different histopathological techniques for
      lymph node harvest from ex-vivo gastrointestinal cancer specimens and to examine
      their influence on: (i) lymph node yield; (ii) positive lymph node detection; and
      (iii) cancer staging. METHOD AND RESULTS: Systematic review of the English
      language literature to 10 October 2011, comparing manual nodal dissection to
      other techniques for lymph node harvest. The methodological quality of included
      studies was assessed. Twenty-seven studies, examining fat clearing, methylene
      blue staining, fat stretching and use of a dedicated pathology assistant, were
      assessed. The methodological quality of the majority of included studies was
      poor. Meta-analysis showed that fat clearing and methylene blue staining
      increased mean lymph node yield by 13 and 15 nodes, respectively, when compared
      to manual dissection. Of the 15 studies reporting positive lymph node count, two
      demonstrated a significant improvement for techniques other than manual
      dissection. Compared to manual dissection, other techniques were not shown to
      influence cancer staging. CONCLUSION: This review has shown that fat clearing and
      methylene blue staining increases the mean lymph node yield from gastrointestinal
      cancer specimens. There is insufficient evidence to suggest that these techniques
      increase positive lymph node count or lead to upstaging.

PMID- 23551434
TI  - Epithelial-mesenchymal transition and clinicopathological correlation in
      craniopharyngioma.
AB  - AIMS: To assess the immunophenotypic changes associated with epithelial
      mesenchymal transition (EMT) in craniopharyngioma, especially at the tumour
      invasive front, and to correlate the findings with clinicopathological features
      and patient outcomes. METHODS AND RESULTS: Forty-two craniopharyngiomas were
      investigated for the presence of EMT markers (vimentin, E-cadherin and beta
      catenin) by immunohistochemistry and western blot. The relationships between
      expression of these markers and various clinicopathological indicators and
      clinical outcomes of the tumours were analysed. There were statistically
      significant differences in the expression of vimentin and E-cadherin-beta-catenin
      between adamantinomatous and papillary variants. The expression of vimentin and E
      cadherin (but not that of beta-catenin) in whole tumour sections was associated
      with tumour recurrence, and with postoperative weight and hypothalamic
      disturbances; the expression of vimentin and E-cadherin-beta-catenin at the
      tumour invasive front was also associated with tumour recurrence, postoperative
      weight, and hypothalamic disturbances. The results from western blotting closely
      matched those of immunohistochemistry. CONCLUSION: Our study demonstrates, for
      the first time, the potential prognostic implications of vimentin, E-cadherin and
      beta-catenin expression in craniopharyngiomas. EMT may represent a crucial
      mechanism in the progression of craniopharyngiomas.

PMID- 23551435
TI  - Early transcatheter aortic valve thrombosis.
AB  - Early valve thrombosis is uncommon after pericardial aortic valve replacement. In
      this report, we describe such a complication after transcatheter aortic valve
      insertion.

PMID- 23551436
TI  - Design and the new BJUI.

PMID- 23551437
TI  - Prostate cancer families - predicting disease before and after the radical.

PMID- 23551438
TI  - Robot-assisted radical prostatectomy: getting your ducks in a row!

PMID- 23551439
TI  - Relationship between overactive bladder (OAB) and irritable bowel syndrome (IBS):
      concurrent disorders with a common pathophysiology?

PMID- 23551440
TI  - Targeting the pro-survival side-effects of androgen-deprivation therapy in
      prostate cancer.

PMID- 23551441
TI  - The emerging role of histone deacetylase (HDAC) inhibitors in urological cancers.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A growing body of
      evidence supports the anti-cancer effect of histone deacetylase inhibitors
      (HDACi) in vitro, via multiple pathways, and many Phase I clinical trials have
      shown them to be well-tolerated in a range of malignancies. Combined therapies,
      including with radiation, present an exciting area of current and planned study.
      This review summarises the evidence to date, including pre-clinical data and
      clinical trials, of the anti-cancer effect of HDACi in urological cancers. It
      provides an overview of epigenetics and the mechanisms of action of HDACi. It
      suggests areas of future development, including the current challenges for the
      successful introduction of HDACi into clinical therapy. Epigenetic modifications
      are known to play a critical role in the development and progression of many
      cancers. The opposing actions of histone deacetylases (HDACs) and histone
      acetyltransferases (HATs) modify chromatin and lead to epigenetic gene
      regulation, in addition to wider effects on non-histone proteins. There is
      growing interest in the clinical application of HDAC inhibitors (HDACi) in
      cancer. HDACi have been shown to inhibit cancer cell growth both in vitro and in
      vivo and recent clinical trials have shown encouraging results in various
      urological cancers. In this review, we discuss the existing evidence and
      potential role for HDACi in urological malignancies, including in combined
      therapies.

PMID- 23551442
TI  - The European Association of Urology Robotic Urology Section (ERUS) survey of
      robot-assisted radical prostatectomy (RARP).
AB  - OBJECTIVE: To evaluate surgeons adherence to current clinical practice, with the
      available evidence, for robot-assisted radical prostatectomy (RARP) and offer a
      baseline assessment to measure the impact of the Pasadena recommendations.
      Recently, the European Association of Urology Robotic Urology Section (ERUS)
      supported the Pasadena Consensus Conference on best practices in RARP. SUBJECTS
      AND METHODS: This survey was performed in January 2012. A specific questionnaire
      was sent, by e-mail, to 145 robotic surgeons who were included in the mailing
      list of ERUS members and working in different urological institutions.
      Participating surgeons were invited to answer a multiple-choice questionnaire
      including 24-items evaluating the main RARP surgical steps. RESULTS: In all, 116
      (79.4%) invited surgeons answered the questionnaire and accepted to participate
      to the ERUS survey. In all, 47 (40.5%) surgeons performed >100 RARPs; 41 (35.3%)
      between 50 and 100, and 28 (24.1%) <50 yearly. The transperitoneal, antegrade
      technique was the preferred approach. Minimising bladder neck dissection and the
      use of athermal dissection of the neurovascular bundles (NVBs) were also popular.
      There was more heterogeneity in the use of energy for seminal vesicle dissection,
      the preservation of the tips of the seminal vesicle and the choice between intra-
      and interfascial planes during the antero-lateral dissection of the NVBs. There
      was also large variability in the posterior and/or anterior reconstruction steps.
      CONCLUSIONS: The present study is the first international survey evaluating
      surgeon preferences during RARP. Considering that the results were collected
      before the publication of the Pasadena recommendations, the data might be
      considered an important baseline evaluation to test the dissemination and effects
      of the Pasadena recommendations in subsequent years.

PMID- 23551443
TI  - Salvage robot-assisted radical prostatectomy.

PMID- 23551444
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.

PMID- 23551445
TI  - Reply: To PMID 23145474.

PMID- 23551446
TI  - Chronic urinary retention in men: how we define it, and how does it affect
      treatment outcome.

PMID- 23551447
TI  - Reply: To PMID 23106771.

PMID- 23551448
TI  - Weight of the resected specimen after transurethral resection as a new predictive
      variable for recurrence of non-muscle-invasive bladder tumour.

PMID- 23551449
TI  - Reply: To PMID 22452619.

PMID- 23551450
TI  - Critical role of prostate biopsy mortality in the number of years of life gained
      and lost within a prostate cancer screening programme.

PMID- 23551451
TI  - Reply: To PMID 22984785.

PMID- 23551452
TI  - Local recurrence after retropubic radical prostatectomy for prostate cancer does
      not exclusively occur at the anastomotic site.

PMID- 23551453
TI  - Reply: To PMID 23551452.

PMID- 23551454
TI  - Safety, efficacy and pitfalls of fibrocyte application in the treatment of
      diabetic foot ulcer.
AB  - Fibrocytes are unique bone marrow-derived cells with great potential in wound
      healing. Hence, the aim of this study was to determine the safety and efficacy of
      the applied circulating fibrocytes in the treatment of non healing diabetic foot
      ulcers. Peripheral blood mononuclear cells were isolated by centrifugation
      through Ficoll-Paque method. After 3 days, the non adherent cells were removed by
      a single, gentle aspiration. Adherent cells were cultured in the same medium for
      10 days. The cells were characterised using mouse anti-human-CD45-fluorescein
      isothiocyanate (FITC) and mouse anti-human-collagen I, and also characterised by
      immunofluorescence microscopy using the above mentioned antibodies. Sterility
      measures were applied for clinical evaluation. Based on the literature review,
      cell transplantation generally requires at least 3 * 10(6) cells regarding
      efficacy measures. As fibrocytes are non proliferating cells, 350 ml patient's
      blood is required to prepare patient-specific serum before cell isolation and
      culture, and 85 ml patient's blood is needed for cell isolation and
      differentiation on cell transplantation applications. In our survey, no diabetic
      patient was inclined to be donor of such blood volume, mainly because of their
      pre-assumption that they are anaemic. It is concluded that fibrocytes do not seem
      to be candidate cells for cell therapy in the treatment of diabetic foot ulcers
      because of the rarity of this cell population in circulation. 

PMID- 23551455
TI  - Transgenic rice seed synthesizing diverse flavonoids at high levels: a new
      platform for flavonoid production with associated health benefits.
AB  - Flavonoids possess diverse health-promoting benefits but are nearly absent from
      rice, because most of the genes encoding enzymes for flavonoid biosynthesis are
      not expressed in rice seeds. In the present study, a transgenic rice plant
      producing several classes of flavonoids in seeds was developed by introducing
      multiple genes encoding enzymes involved in flavonoid synthesis, from
      phenylalanine to the target flavonoids, into rice. Rice accumulating naringenin
      was developed by introducing phenylalanine ammonia lyase (PAL) and chalcone
      synthase (CHS) genes. Rice producing other classes of flavonoids, kaempferol,
      genistein, and apigenin, was developed by introducing, together with PAL and CHS,
      genes encoding flavonol synthase/flavanone-3-hydroxylase, isoflavone synthase,
      and flavone synthases, respectively. The endosperm-specific GluB-1 promoter or
      embryo- and aleurone-specific 18-kDa oleosin promoters were used to express these
      biosynthetic genes in seed. The target flavonoids of naringenin, kaempferol,
      genistein, and apigenin were highly accumulated in each transgenic rice,
      respectively. Furthermore, tricin was accumulated by introducing hydroxylase and
      methyltransferase, demonstrating that modification to flavonoid backbones can be
      also well manipulated in rice seeds. The flavonoids accumulated as both aglycones
      and several types of glycosides, and flavonoids in the endosperm were deposited
      into PB-II-type protein bodies. Therefore, these rice seeds provide an ideal
      platform for the production of particular flavonoids due to efficient
      glycosylation, the presence of appropriate organelles for flavonoid accumulation,
      and the small effect of endogenous enzymes on the production of flavonoids by
      exogenous enzymes. 

PMID- 23551456
TI  - The treatment of children suffering from chronic myelogenous leukemia: a
      comparison of the result of treatment with imatinib mesylate and allogeneic
      hematopoietic stem cell transplantation.
AB  - HSCT is the only proven treatment option for CML, a rare disease in children.
      Recently, there are promising reports on the advantageous effect of imatinib
      mesylate for pediatric patients with CML. We conducted a retrospective study on
      33 pediatric patients suffering from CML. Fourteen underwent HSCT and the rest
      were treated with imatinib. With a median follow-up of 24 months, the two-yr OS
      in the HSCT group and the imatinib group was 84% and 87%, respectively (p =
      0.714). The probabilities of two-yr DFS were 59% in the HSCT group and 82% in the
      imatinib group, either (p = 0.880). Relapse occurred in 5 (35.7%) patients of the
      HSCT group, and 8 (42.1%) patients showed relapse in the imatinib group. Among
      nine patients who died, five were in the HSCT group and the rest were in the
      imatinib group. The probability of relapse in the patients of the imatinib group
      followed up for several consecutive years may be higher than observed in the HSCT
      group, so we cannot easily conclude which way is more reliable.

PMID- 23551457
TI  - Rehospitalization and emergency department use rates before and after vagus nerve
      stimulation for epilepsy: use of state databases to provide longitudinal data
      across multiple clinical settings.
AB  - OBJECTIVES: Data regarding rehospitalization and emergency department (ED) visits
      following vagus nerve stimulation (VNS) present data analysis challenges. We
      present a method that uses California's multiple databases to more completely
      assay VNS efficacy. MATERIALS AND METHODS: The Healthcare Cost and Utilization
      Project's California Inpatient and Ambulatory Surgery databases were assayed for
      all VNS surgeries from 2005 to 2009. Patients were selected by epilepsy diagnosis
      codes and VNS procedure codes. Patients (total N = 629) were tracked across
      multiple databases using unique identifiers. Thirty-day and one-year post
      implantation rates of VNS complication and healthcare visits were abstracted,
      along with one-year preoperative hospital and ED use. Statistics included
      correction for multiple comparisons. RESULTS: The one-year reoperation rate for
      adult patients (N = 536) was 3.9%; during the second year, an additional 3.2% of
      patients had reoperations. Within the first 30 days, <2% of patients experienced
      a complication. Four percent of patients were readmitted to a hospital, and 11.6%
      of patients visited an ED. The most common reason for rehospitalization or ED
      visit was seizure. In the first year after VNS, total seizure-related visits
      (hospitalization and ED) were 17% lower (2.12 visits per year to 1.71; p = 0.03).
      In the second year following VNS, seizure-related visits were 42% lower (2.21
      visits per year to 1.27, p = 0.01). Pediatric patients (N = 93) had comparable
      results. CONCLUSIONS: VNS surgery has low rates of complications and reoperations
      and is associated with reduced incidence of seizure-related ED visits and
      hospital admissions in the first and second postoperative years.

PMID- 23551458
TI  - Visualizing the production and arrangement of peptidoglycan in Gram-positive
      cells.
AB  - Decades of study have revealed the fine chemical structure of the bacterial
      peptidoglycan cell wall, but the arrangement of the peptidoglycan strands within
      the wall has been challenging to define. The application of electron
      cryotomography (ECT) and new methods for fluorescent labelling of peptidoglycan
      are allowing new insights into wall structure and synthesis. Two articles in this
      issue examine peptidoglycan structures in the model Gram-positive species
      Bacillus subtilis. Beeby et al. combined visualization of peptidoglycan using ECT
      with molecular modelling of three proposed arrangements of peptidoglycan strands
      to identify the model most consistent with their data. They argue convincingly
      for a Gram-positive wall containing multiple layers of peptidoglycan strands
      arranged circumferentially around the long axis of the rod-shaped cell, an
      arrangement similar to the single layer of peptidoglycan in similarly shaped Gram
      negative cells. Tocheva et al. examined sporulating cells using ECT and
      fluorescence microscopy to demonstrate the continuous production of a thin layer
      of peptidoglycan around the developing spore as it is engulfed by the membrane of
      the adjacent mother cell. The presence of this peptidoglycan in the intermembrane
      space allows the refinement of a model for engulfment, which has been known to
      include peptidoglycan synthetic and lytic functions.

PMID- 23551459
TI  - Undernutrition among infants less than 6 months of age: an underestimated public
      health problem in India.
AB  - In India most childhood nutrition recommendations and interventions are still not
      focused on infants under 6 months. Secondary data analyses of National Family
      Health Survey-3 data from India were analysed to compare the prevalence of
      wasting, stunting and underweight in infants less than 6 months and 6-59 months.
      Our results revealed that wasting was higher (31%) in infants less than 6 months
      (P < 0.05) as compared with children between 6 and 59 months. Thirteen per cent
      of infants less than 6 months had severe wasting, 30% were underweight and 20%
      were stunted. Most infants (69%) were exclusively breastfed (EB) for the first 2
      months, but exclusive breastfeeding dropped to 50% at 2-3 months and to 27% at 4
      5 months. There was no statistically significant difference in wasting and
      stunting in the EB and not exclusively breastfed (NEB) groups. Significantly
      fewer EB infants were underweight (28%) compared with NEB infants (31%) (P =
      0.030). However, among EB children, 29% had wasting and 21% were stunted. Eleven
      per cent of EB infants were severely underweight, 13% were severely wasted and 9%
      were severely stunted. Diarrhoea was significantly lower among EB infants
      compared with NEB infants (P < 0.05). We conclude that infants less than 6 months
      of age are vulnerable to suffer from acute severe malnutrition irrespective of
      their breastfeeding status and need to be seriously considered for inclusion in
      national guidelines for early detection and management of undernutrition. 

PMID- 23551460
TI  - Long-term efficacy and safety of two different rhythm control strategies in
      elderly patients with symptomatic persistent atrial fibrillation.
AB  - BACKGROUND: We prospectively compared the efficacy, safety, and quality of life
      (QoL) impact of catheter ablation versus antiarrhythmic drugs (AAD) in elderly
      patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: Four
      hundred and twelve consecutive patients, aged >= 70 years, underwent ablation
      (Group A, 153 patients) or AAD (Group B, 259 patients). Study endpoints:
      treatment failure (any AF/AT lasting >30 seconds) and treatment-related adverse
      events (acute when <=1 month of procedure and long term when >1 month). At a
      follow-up of 60 +/- 17 months, 43% and 46% patients in Group B versus 58% and 76%
      in Group A were in sinus rhythm (SR), respectively, after one (P = 0.003) and 2
      procedures (P < 0.001). Fifteen acute adverse events occurred (6.7% in Group A vs
      1% in Group B, P < 0.001), mainly periprocedural cerebral thromboembolism (3.3%
      in Group A vs 0.7% in Group B, P = 0.058). Previous TIA/stroke resulted the only
      independent predictor of periprocedural cerebrovascular accidents (OR 1.2, 95%IC
      1.1-1.3). At follow-up, 74 long-term adverse events occurred (7.7% in Group A vs
      23.9% in Group B, P < 0.001) with Group B patients more often experiencing AAD
      related adverse events (12.7% vs 2.6%, P < 0.001). Group A and absence of AF/AT
      recurrences significantly improved QoL scores (P < 0.001). CONCLUSIONS: In
      elderly persistent AF patients, catheter ablation is more effective in
      maintaining SR and in improving QoL than AAD but is affected by a higher risk of
      embolic complications, particularly in patients with previous TIA/stroke. Over
      time, Group A patients more likely discontinued AAD with a reduction of long-term
      adverse events.

PMID- 23551461
TI  - Using genomic data to revisit an early example of reproductive character
      displacement in Haitian Anolis lizards.
AB  - The pattern of reproductive character displacement (RCD)-in which traits
      associated with reproductive isolation are more different where two species occur
      together than where they occur in isolation-is frequently attributed to
      reinforcement, a process during which natural selection acting against
      maladaptive mating events leads to enhanced prezygotic isolation between species
      or incipient species. One of the first studies of RCD to include molecular
      genetic data was described 40 years ago in a complex of Haitian trunk anole
      lizards using a small number of allozyme loci. In this example, Anolis caudalis
      appears to experience divergence in the color and pattern of an extensible throat
      fan, or dewlap, in areas of contact with closely related species at the northern
      and southern limits of its range. However, this case study has been largely
      overlooked for decades; meanwhile, explanations for geographic variation in
      dewlap color and pattern have focused primarily on adaptation to local signalling
      environments. We reinvestigate this example using amplified fragment length
      polymorphism (AFLP) genome scans, mtDNA sequence data, information on dewlap
      phenotypes and GIS data on environmental variation to test the hypothesis of RCD
      generated by reinforcement in Haitian trunk anoles. Together, our phenotypic and
      genetic results are consistent with RCD at the southern and northern limits of
      the range of A. caudalis. We evaluate the evidence for reinforcement as the
      explanation for RCD in Haitian trunk anoles, consider alternative explanations
      and provide suggestions for future work on the relationship between dewlap
      variation and speciation in Haitian trunk anoles. 

PMID- 23551463
TI  - Interactions between angiotensin AT1 receptor antagonists and second-generation
      antiepileptic drugs in the test of maximal electroshock.
AB  - The anticonvulsant activity of angiotensin AT1 receptor antagonists, losartan (2
      n-butyl-4-chloro-5-hydroxymethyl-1-[(2'(1H-tetrazol-5-yl)-biphenil-4
      yl)methyl]imidazole) and telmisartan (49-[(1,49-dimethyl-29-propyl[2,69-bi-1H
      benzimidazo]-19-yl)methyl]-[1,19-biphenyl]-2-carboxylic acid), has been reported
      recently. It is suggested that AT1 receptor antagonists may affect the protective
      action of antiepileptic drugs. The aim of this study was to determine the
      influence of losartan and telmisartan on the anticonvulsant activity of some
      second-generation antiepileptics (lamotrigine - LTG, oxcarbazepine - OXC, and
      topiramate - TPM). For this purpose, the maximal electroshock seizure (MES) test
      in mice was used. Additionally, the drug combinations were checked for adverse
      effects in the passive avoidance and chimney tests. In the MES test, losartan at
      the doses of 30 and 50 mg/kg, administered intraperitoneally (i.p.), potentiated
      the protective action of LTG (P < 0.01). This interaction was not accompanied by
      a significant change of LTG level either in plasma or in the brain. Telmisartan
      at the dose of 30 mg/kg i.p. enhanced the anticonvulsant action of TPM (P <
      0.01). However, this interaction was pharmacokinetic in nature, as telmisartan
      significantly increased plasma and total brain concentrations of TPM (P < 0.001).
      The combinations of AT1 receptor antagonists with antiepileptic drugs did not
      affect retention in the passive avoidance test or motor coordination in the
      chimney test. The potentiation of the anticonvulsant action of LTG by losartan
      probably on account of pharmacodynamic interactions, make this combination
      important for further experimental and clinical studies. The combination of
      telmisartan and TPM is less beneficial due to pharmacokinetic interactions.

PMID- 23551466
TI  - Quad bikes: tobacco on four wheels.

PMID- 23551467
TI  - Aboriginal health and the Australian Constitution: how do we fix them both?

PMID- 23551462
TI  - Neutrophil activity in chronic venous leg ulcers--a target for therapy?
AB  - Chronic venous leg ulcers (CVLUs) affect approximately 600,000 people annually in
      the United States and accrue yearly treatment costs of US $2.5-5 billion. As the
      population ages, demands on health care resources for CVLU treatments are
      predicted to drastically increase because the incidence of CVLUs is highest in
      those >=65 years of age. Furthermore, regardless of current standards of care,
      healing complications and high recurrence rates prevail. Thus, it is critical
      that factors leading to or exacerbating CVLUs be discerned and more effective,
      adjuvant, evidence-based treatment strategies be utilized. Previous studies have
      suggested that CVLUs' pathogenesis is related to the prolonged presence of high
      numbers of activated neutrophils secreting proteases in the wound bed that
      destroy growth factors, receptors, and the extracellular matrix that are
      essential for healing. These events are believed to contribute to a chronically
      inflamed wound that fails to heal. Therefore, the purpose of this project was to
      review studies from the past 15 years (1996-2011) that characterized neutrophil
      activity in the microenvironment of human CVLUs for new evidence that could
      explicate the proposed relationship between excessive, sustained neutrophil
      activity and CVLUs. We also appraised the strength of evidence for current and
      potential therapeutics that target excessive neutrophil activity.

PMID- 23551468
TI  - Policy scorecard for gender mainstreaming: gender equity in health policy.
AB  - OBJECTIVES: To examine whether gender mainstreaming for women's health is
      included in national and state health policies. METHODS: A policy analysis tool
      (Policy Scorecard) was developed and then applied to Australia's National Health
      Priority Areas as well as policies of three Australian States. RESULTS: Despite
      Australia's leadership in women's health policy, its health policies are largely
      devoid of gender equity concerns at both national and state levels. Mainstreaming
      of gender equity outcomes has not yet occurred in Australia. CONCLUSIONS:
      Applying the Policy Scorecard for Gender Mainstreaming to local and country
      specific policies is revealing of governments' commitment to women, and how well
      gender equity goals are embedded into policies and programs. Policy analysis
      using this gender-sensitive Policy Scorecard provides opportunities for advocacy
      to advance women's health and gender equity at any level of government, in any
      country.

PMID- 23551469
TI  - A cross-sectional survey of health risk behaviour clusters among a sample of
      socially disadvantaged Australian welfare recipients.
AB  - OBJECTIVE: To examine the prevalence and clustering of six health risk behaviours
      (smoking, alcohol, inadequate sun protection, physical inactivity, and inadequate
      fruit and vegetable consumption) among severely disadvantaged individuals.
      METHODS: A cross-sectional touch screen computer survey was conducted with 383
      clients attending a social and community welfare organisation in New South Wales.
      Participants were assessed on smoking status, alcohol consumption, fruit and
      vegetable consumption, physical activity, sun protection and socio-demographic
      characteristics. Descriptive statistics, factor analysis and logistic regression
      were used to assess the prevalence, clustering and socio-demographic predictors
      of health risk behaviours. RESULTS: Ninety-eight per cent of the participants
      reported inadequate vegetable consumption, 62.7% reported inadequate fruit
      consumption, 82.5% reported inadequate sun protection, 61.7% smoked tobacco,
      51.4% consumed alcohol at risky levels and 36.5% were insufficiently active. Most
      participants (87%) reported three or more risk behaviours. Male participants,
      younger participants and those with lower education were more likely to smoke
      tobacco and consume alcohol. CONCLUSIONS: The prevalence of health risk
      behaviours among a sample of typically hard-to-reach, severely disadvantaged
      individuals is extremely high. IMPLICATIONS: Future intervention development
      should take into account the likelihood of health risk clustering among severely
      disadvantaged groups.

PMID- 23551470
TI  - Engagement and recruitment of Maori and non-Maori people of advanced age to
      LiLACS NZ.
AB  - OBJECTIVES: Life and Living in Advanced Age: A Cohort Study in New Zealand
      (LiLACS NZ) aims to determine the predictors of successful advanced ageing and
      understand the trajectories of wellbeing in advanced age. This paper reports
      recruitment strategies used to enrol 600 Maori aged 80-90 years and 600 non-Maori
      aged 85 years living within a defined geographic boundary. METHODS: Electoral
      roll and primary health lists of older people were used as a base for
      identification and recruitment, supplemented by word of mouth, community
      awareness raising and publicity. A Kaupapa Maori method was used to recruit Maori
      with: dual Maori and non-Maori research leadership; the formation of a support
      group; local tribal organisations and health providers recruiting participants;
      and use of the Maori language in interviews. Non-Maori were recruited through
      local health and community networks. Six organisations used differing strategies
      to invite older people to participate in several ways: complete full or partial
      interviews; complete physical assessments; provide a blood sample and provide
      access to medical records. RESULTS: During 14 months in 2010-2011, 421 of 766
      (56%) eligible Maori and 516 of 870 (59%) eligible non-Maori were enrolled.
      Participation and contribution of information varied across the recruitment
      sites. CONCLUSION: Attention to appropriate recruitment techniques resulted in an
      acceptable engagement and recruitment for both Maori and non-Maori of advanced
      age in a longitudinal cohort study. IMPLICATIONS: There is high potential for
      meaningful results useful for participants, their whanau and families, health
      agencies, planners and policy.

PMID- 23551471
TI  - Prescribing databases can be used to monitor trends in opioid analgesic
      prescribing in Australia.
AB  - OBJECTIVE: There has been increased use of prescription opioid analgesics in
      Australia in the past 20 years with increasing evidence of related problems. A
      number of data sources collect information about the dispensed prescribing for
      opioid medications, but little is known about the extent to which these data
      sources agree on levels of opioid prescribing. METHODS: In Queensland, all opioid
      prescriptions (S8 prescriptions) dispensed by community pharmacies must be
      submitted to the Drugs of Dependence Unit (DDU). This potentially comprises a
      'gold standard' against which other data sources may be judged. There are two
      national data sources: the Pharmaceutical Benefits Schedule (PBS) for all
      medications subsidised by government; and an annual national survey of
      representative pharmacies, which assesses non-subsidised opioid prescribing. We
      examined the agreement between these data sources. RESULTS: The three data
      sources provided consistent estimates of use over time. The correlations between
      different data sources were high for most opioid analgesics. There was a
      substantial (60%) increase in the dispensed use of opioid analgesics and a 180%
      increase in the dispensed use of oxycodone over the period 2002-2009. Tramadol
      was the most used opioid-like medication. CONCLUSIONS: Since 2002 different data
      sources reveal similar trends, namely a substantial increase in the prescribing
      of opioid medications. With few exceptions, the conclusions derived from using
      any of these data sources were similar. IMPLICATIONS: Improved access to PBS data
      for relevant stakeholders could provide an efficient and cost-effective way to
      monitor use of prescription opioid analgesics.

PMID- 23551472
TI  - Beyond the paper trail: using technology to reduce escalating harms from opioid
      prescribing in Australia.
AB  - OBJECTIVE: The paper highlights the extent of pharmaceutical drug misuse problems
      in Australia and explores how pharmaceutical opioid misuse could be reduced by
      implementation of a technological tool: a prescription co-ordination program
      (PCP). The paper explores how enhancements to existing computer-assisted clinical
      decision support systems through real-time, on-line information to prescribers,
      pharmacists and regulators could address drug-seeking and improve the quality use
      of medicines. APPROACH: Trends in national and international prescription opioid
      use and related harms are examined with attention directed to drug-seeking
      behaviour and intentional misuse. The international literature concerning PCPs is
      reviewed and implications for technological advances in Australia are outlined.
      CONCLUSION: Australia has a burgeoning problem associated with the misuse of
      pharmaceutical opioids. There is increased recognition of a range of iatrogenic
      harms. A number of factors limit Australia's response capacity including lack of
      technological capacity to provide on-line, real-time information for prescribers
      and pharmacists. IMPLICATIONS: Providing prescribers, pharmacists and regulators
      with on-line, real-time information about patients' prescription opioid use will
      improve the quality use of medicines. A national system is required to co
      ordinate data on Pharmaceutical Benefits Scheme, Repatriation Pharmaceutical
      Benefits Scheme and unsubsidised medicines, including private prescriptions.
      Pharmaceutical opioids are not the only medicines subject to misuse and therefore
      the need to capture data on other relevant medicines is also addressed.

PMID- 23551473
TI  - Healthcare utilisation and disclosure of injecting drug use among clients of
      Australia's needle and syringe programs.
AB  - BACKGROUND: People who inject drugs (PWID) report limited access to healthcare,
      and may avoid disclosing drug use. Health service utilisation was examined among
      participants in the Australian Needle and Syringe Program Survey (ANSPS), an
      annual cross-sectional sero-survey of needle syringe program (NSP) attendees.
      METHODS: An anonymous questionnaire was self-completed by 2,395 NSP clients
      throughout Australia. Multivariable logistic regressions identified variables
      independently associated with (i) disclosure of injecting to the most recent
      healthcare provider; and (ii) recent presentation to emergency departments.
      RESULTS: Seventy-eight percent of participants reported accessing healthcare in
      the preceding 12 months. Reasons for presentation included general health issues
      (46%); medication seeking (17%); and both (37%). Participants who recently
      accessed healthcare or had previously visited their most recent provider were
      more likely to disclose injecting drug use. Participants presenting to a GP or
      medical centre were less likely than others to disclose injecting. Those
      accessing emergency departments were more likely to report recent imprisonment.
      CONCLUSIONS: Despite Australia's universal healthcare system and harm reduction
      policies, NSP-participants remain reluctant to disclose injecting, potentially
      hindering appropriate care and highlighting the need for multiple entry points to
      the healthcare system, including NSPs and opioid substitution therapy clinics.

PMID- 23551474
TI  - "When you're desperate you'll ask anybody": young people's social sources of
      tobacco.
AB  - OBJECTIVES: This study sought to examine young New Zealand smokers' access to
      social supplies of cigarettes. METHODS: A qualitative investigation using 10
      focus groups with 66 current young smokers, aged between 15 and 17 years, was
      conducted throughout New Zealand, between October and December 2011. Transcripts
      from the focus groups were analysed using NVivo to code the data, from which
      common themes and critical issues were identified. RESULTS: Family was one of the
      main sources of tobacco for the young smokers in this study and parents were the
      leading source, often purchasing tobacco for their children to smoke. Sharing
      tobacco within groups of friends was also very common. Additional methods were
      used when young smokers were desperate, including stealing, 'butt scabbing' and
      asking strangers. CONCLUSIONS: Both family and social networks continue to
      support smoking and supply tobacco to young people. While these networks operate,
      young people will continue to smoke, despite increased regulations on commercial
      sales to minors. IMPLICATIONS: Restrictions on commercial sales of tobacco to
      minors are increasing; however, many young people use multiple sources of
      tobacco, including social sources. It is likely that young people will
      increasingly use these social sources in the future. Interventions other than
      purchase restrictions are important for reducing minors' access to tobacco.

PMID- 23551475
TI  - Ethnic, socioeconomic and geographical inequalities in road traffic injury rates
      in the Auckland region.
AB  - OBJECTIVE: To describe ethnic, socioeconomic and geographical differences in road
      traffic injury (RTI) within Auckland, New Zealand's largest city. METHODS: We
      analysed rates of RTI deaths and non-fatal hospital admissions using the New
      Zealand Mortality Collection and the National Minimum Data Set 2000-08. Poisson
      regression examined the association of age, gender, prioritised ethnicity and
      small area deprivation (New Zealand Index of Deprivation) with RTI rates, and RTI
      rates were mapped for 21 local board areas within the Auckland region. RESULTS:
      While RTI rates increased with levels of deprivation in all age groups, the
      gradient was steepest among children (9% increase/decile) and adults aged 25-64
      years (11% increase/decile). In all age groups, RTI risk was highest among Maori.
      Pacific children had an elevated risk of RTI compared with the NZ European/Other
      group, but Pacific youth (15-24 years) and adults (25-64 years) had a lower risk.
      While RTI rates were generally higher for those living in rural local board
      areas, all but one local board in the southern Auckland urban area had among the
      highest rates. CONCLUSIONS: There are substantial ethnic, socioeconomic and
      geographic inequalities in RTI risk in the Auckland region, with high rates among
      Maori (all ages), Pacific children, people living in socioeconomically deprived
      neighbourhoods, the urban south and rural regions. IMPLICATIONS: To meet the
      vision of regional plans, road safety efforts must prioritise vulnerable
      communities at greatest risk of RTI, and implement and monitor the effectiveness
      of strategies that specifically include a focus on reducing inequalities in RTI
      rates.

PMID- 23551476
TI  - Injuries leading to hospitalisation in the first year of life: analysis by
      trimester of age using coded data and textual description.
AB  - OBJECTIVE: To describe unintentional injuries to children aged less than one
      year, using coded and textual information, in three-month age bands to reflect
      their development over the year. METHODS: Data from the Queensland Injury
      Surveillance Unit was used. The Unit collects demographic, clinical and
      circumstantial details about injured persons presenting to selected emergency
      departments across the State. Only injuries coded as unintentional in children
      admitted to hospital were included for this analysis. RESULTS: After editing,
      1,082 children remained for analysis, 24 with transport-related injuries. Falls
      were the most common injury, but becoming proportionately less over the year,
      whereas burns and scalds and foreign body injuries increased. The proportion of
      injuries due to contact with persons or objects varied little, but poisonings
      were relatively more common in the first and fourth three-month periods.
      Descriptions indicated that family members were somehow causally involved in 16%
      of injuries. Our findings are in qualitative agreement with comparable previous
      studies. CONCLUSION: The pattern of injuries varies over the first year of life
      and is clearly linked to the child's increasing mobility. IMPLICATIONS: Injury
      patterns in the first year of life should be reported over shorter intervals.
      Preventive measures for young children need to be designed with their rapidly
      changing developmental stage in mind, using a variety of strategies, one of which
      could be opportunistic developmentally specific education of parents.

PMID- 23551477
TI  - Australian quad bike fatalities: what is the economic cost?
AB  - OBJECTIVE: To determine the economic costs associated with all quad bike-related
      fatalities in Australia, 2001 to 2010. METHODS: A human capital approach to
      establish the economic costs of quad bike related fatalities to the Australian
      economy. The model included estimates on loss of earnings due to premature death
      and direct costs based on coronial records for ambulance, police, hospital,
      premature funeral, coronial and work safety authority investigation, and death
      compensation costs. All costs were calculated to 2010 dollars. RESULTS: The
      estimated total economic cost associated with quad bike fatalities over this
      period was $288.1 million, with an average cost for each fatality of $2.3
      million. When assessing the average cost of incidents between age cohorts, those
      aged 25-34 years had the lowest number of fatalities but had the highest average
      cost ($4.2 million). CONCLUSIONS: Quad bike fatalities have a significant
      economic impact on Australian society that is increasing. Implications : Given
      the high cost to society, interventions to address quad bike fatalities have the
      potential to be highly cost-effective. Such interventions should focus on design
      approaches to improve the safety of quad bikes in terms of stability and
      protection in the event of a rollover. Additionally, relevant policy (e.g. no
      children under 16 years riding quads, no passengers) and intervention approaches
      (e.g. training and use of helmets) must also support the design modifications.

PMID- 23551478
TI  - Older fallers attended to by an ambulance but not transported to hospital: a
      vulnerable population at high risk of future falls.
AB  - OBJECTIVE: This prospective cohort study describes older non-transported fallers
      seen by the Ambulance Service of New South Wales (ASNSW), quantifies the level of
      risk and identifies predictors of future falls and ambulance use. METHODS:
      Participants were 262 people aged 70 years or older with a fall-related ASNSW
      attendance who were not transported to an emergency department. They completed a
      questionnaire about health, medical and physical factors previously associated
      with falling. Falls were monitored for six months after ambulance attendance with
      monthly fall calendars. RESULTS: Participants had a high prevalence of chronic
      medical conditions, functional limitations and past falls. During follow-up, 145
      participants (58%) experienced 488 falls. Significant predictors of falls during
      follow-up were three or more falls in the past year, being unable to walk more
      than 10 minutes without resting, and requiring assistance for personal-care
      activities of daily living (ADLs). Sixty-two participants (25%) required repeat,
      fall-related ambulance attendance during the study. Predictors of repeat
      ambulance use were: 3+ falls in past year, requiring assistance for personal-care
      ADLs and having disabling pain in past month. CONCLUSIONS: Older, non-transported
      fallers seen by the ASNSW are a vulnerable population with high rates of chronic
      health conditions. IMPLICATIONS: Onward referral for preventive interventions may
      reduce future falls and ambulance service calls.

PMID- 23551479
TI  - How do Indigenous Australians experience cannabis withdrawal?

PMID- 23551480
TI  - Examination of the completeness of routinely collected antenatal care data in New
      South Wales.

PMID- 23551481
TI  - Hepatitis D is rare or non-existent in hepatitis B virus-infected Indigenous
      Australians in the Northern Territory.

PMID- 23551482
TI  - Accuracy of National Health Index numbers for Pacific people in NZ.

PMID- 23551483
TI  - Too many left at risk by current folic acid supplementation use: evidence from
      Growing Up in New Zealand.

PMID- 23551484
TI  - Costs of being a carer: labour force participation and lost earnings among older
      working-aged Australians.

PMID- 23551485
TI  - Community development in practice: reflections on power sharing between a
      community health centre and group of unemployed men.

PMID- 23551486
TI  - Goal-proximity decision-making.
AB  - Reinforcement learning (RL) models of decision-making cannot account for human
      decisions in the absence of prior reward or punishment. We propose a mechanism
      for choosing among available options based on goal-option association strengths,
      where association strengths between objects represent previously experienced
      object proximity. The proposed mechanism, Goal-Proximity Decision-making (GPD),
      is implemented within the ACT-R cognitive framework. GPD is found to be more
      efficient than RL in three maze-navigation simulations. GPD advantages over RL
      seem to grow as task difficulty is increased. An experiment is presented where
      participants are asked to make choices in the absence of prior reward. GPD
      captures human performance in this experiment better than RL.

PMID- 23551487
TI  - Cold shock protein 1 chaperones mRNAs during translation in Arabidopsis thaliana.
AB  - RNA binding proteins (RBPs) function post-transcriptionally to fine-tune gene
      regulation. Arabidopsis thaliana has four Gly-rich, zinc finger-containing RBPs
      called cold shock proteins 1-4 (CSP1-CSP4), that possess an evolutionary
      conserved cold shock domain. Here, we determined that CSP1 associates with
      polyribosomes (polysomes) via an RNA-mediated interaction. Both the abundance and
      polysomal co-fractionation of CSP1 was enhanced in the cold (4 degrees C), but
      did not influence global levels of polysomes, which were minimally perturbed by
      above freezing cold temperatures. Using a polyclonal antiserum, CSP1 was co
      immunopurified with several hundred transcripts from rosettes of plants
      cultivated at 23 degrees C or transferred to 4 degrees C for 12 h. CSP1
      associated mRNAs were characterized by G+C-rich 5' untranslated regions and gene
      ontologies related to cellular respiration, mRNA binding and translation. The
      majority of the CSP1-associated mRNAs were constitutively expressed and stable in
      the cold. CSP1 abundance was correlated with improved translation of ribosomal
      protein mRNAs during cold stress and improved maintenance of homeostasis and
      translation of mRNAs under water-deficit stress. In summary, CSP1 selectively
      chaperones mRNAs, providing translational enhancement during stress.

PMID- 23551488
TI  - Pre to post-dialysis plasma sodium change better predicts clinical outcomes than
      dialysate to plasma sodium gradient in quotidian hemodialysis.
AB  - Sodium balance across a hemodialysis treatment influences interdialytic weight
      gain (IDWG), pre-dialysis blood pressure, and the occurrence of intradialytic
      hypotension, which associate with patient morbidity and mortality. In thrice
      weekly conventional hemodialysis patients, the dialysate sodium minus pre
      dialysis plasma sodium concentration (deltaDPNa+) and the post-dialysis minus pre
      dialysis plasma sodium (deltaPNa+) are surrogates of sodium balance, and are
      associated with both cardiovascular and all-cause mortality. However, whether
      deltaDPNa+ or deltaPNa+ better predicts clinical outcomes in quotidian dialysis
      is unknown. We performed a retrospective analysis of clinical and demographic
      data from the Southwestern Ontario Regional Home Hemodialysis program, of all
      patients since 1985. In frequent nocturnal hemodialysis, deltaPNa+ was superior
      to deltaDPNa+ in predicting IDWG (R(2)=0.223 vs. 0.020, P=0.002 vs. 0.76),
      intradialytic change in systolic (R(2)=0.100 vs. 0.002, P=0.02 vs. 0.16) and
      diastolic (R(2)=0.066 vs. 0.019, P=0.02 vs. 0.06) blood pressure, and
      ultrafiltration rate (R(2)=0.296 vs. 0.036, P=0.001 vs. 0.52). In short hours
      daily hemodialysis, deltaDPNa+ was better than deltaPNa+ in predicting
      intradialytic change in diastolic blood pressure (R(2)=0.101 vs. 0.003, P=0.02
      vs. 0.13). However, deltaPNa+ was better than deltaDPNa+ in predicting IDWG
      (R(2)=0.105 vs. 0.019, P=0.04 vs. 0.68) and pre-dialysis systolic blood pressure
      (R(2)=0.103 vs. 0.007, P=0.02 vs. 0.82). We also found that the intradialytic
      blood pressure fall was greater in frequent nocturnal hemodialysis patients than
      in short hours daily patients, when exposed to a dialysate to plasma sodium
      gradient. These results provide a basis for design of prospective trials in
      quotidian dialysis modalities, to determine the effect of sodium balance on
      cardiovascular outcome.

PMID- 23551489
TI  - Predictors of expressed emotion, burden and quality of life in relatives of
      Mexican patients with psychosis.
AB  - Expressed emotion, burden and quality of life of relatives received attention
      because of the increasing interest in predicting and preventing relapse in
      psychotic patients; but they have subsequently acquired interest of their own as
      important aspects of families' psychological well-being. The study explores
      whether the psychological distress and illness perception of a sample of
      relatives of Mexican patients with psychosis can predict their levels of
      expressed emotion, burden and quality of life above patients' clinical and
      functional status. Sixty-five patient-relative dyads were interviewed. Relatives
      self-reported on expressed emotion, burden, quality of life, psychological
      distress and illness perception. Patients' clinical and functional status was
      rated by an interviewer. Pearson correlations and hierarchical multiple linear
      regressions were used for statistical analyses. Patients' functional status and
      relatives' psychological distress were significantly associated with expressed
      emotion, burden and quality of life. Patients' clinical status and relatives'
      illness perception were most strongly related to expressed emotion and burden.
      Relatives' psychological distress and illness perception dimensions predicted
      both burden and quality of life, over and above patients' clinical and functional
      status. Results underscore the relatives' need of support to overcome their own
      distress and concerns about the illness, for the psychological well-being of both
      patients and relatives.

PMID- 23551490
TI  - Rotating titanium brush for plaque removal from rough titanium surfaces--an in
      vitro study.
AB  - OBJECTIVES: The purpose of this study was the evaluation of the effectiveness of
      plaque removing of a new rotating brush made of titanium in comparison with the
      cleaning procedure with steel curettes. MATERIALS AND METHODS: Plaque was
      collected by six volunteers for 48 h. A total of 60 samples were randomly
      designated to two groups: the test group TiBrush and the control group with steel
      curettes. The residual plaque area (RPA) and the treatment time were determined
      as parameters. Scanning electron microscopy (SEM) was performed for detecting
      possible damages of the treatment procedures. RESULTS: The mean RPA within the
      TiBrush group (8.57 +/- 4.85%) was significant lower than in the control group
      (28.99 +/- 5.51%), while the mean treatment time was also significant lower in
      the TiBrush group (176.7 +/- 15.2 sec) in comparison with the steel curettes
      (303.5 +/- 11.5 sec). The outcomes of SEM analysis showed no surface alteration
      after TiBrush treatment. CONCLUSIONS: Within the limits of this study, this
      investigation concludes that TiBrush seems to be more effective in plaque
      removing capacity, while being gentler to the implant surface than the processing
      with steel curettes. These promising results could hold out an improvement of
      conventional periimplantitis treatment. Further studies are needed to prove these
      outcomes.

PMID- 23551491
TI  - A review of current concepts in radiofrequency chondroplasty.
AB  - Radiofrequency (RF) chondroplasty is a promising treatment of chondral defects.
      The purpose of this study is to summarize current literature reporting the use of
      radiofrequency energy as an alternative treatment to mechanical shaving in
      chondroplasty. This review depicts the basic understanding of RF energy in
      ablating cartilage while exploring the basic science, laboratory evidence and
      clinical effectiveness of this form of chondroplasty. Laboratory studies have
      indicated that RF energy decreases inflammatory markers in the cartilage as well
      as providing optimal results with smoothing of chondral clefts. There have been
      concerns of chondrolysis due to heat damage of chondrocytes; however, this is
      unsubstantiated in clinical studies. These clinical trials have highlighted that
      RF energy is a safe and efficacious method of chondroplasty when compared to the
      mechanical shaving technique.

PMID- 23551492
TI  - The development and psychometric evaluation of the Chinese version of the
      Maternal Attachment Inventory.
AB  - AIMS AND OBJECTIVES: To develop the Maternal Attachment Inventory (MAI) into
      Chinese and assess its psychometric properties. BACKGROUND: The MAI measures of
      maternal affectionate attachment. This scale displays the most appropriate
      indicators associated with attachment and has been widely adopted in different
      fields for measuring maternal-infant attachment. DESIGN: Cross-sectional survey
      design. METHODS: The study was carried out in two clinics. From the accessible
      population of 507 samples, a simple random sampling method of selection was used
      to randomly choose 200 names of mothers at 4-8 months after delivery using a
      computer. One hundred and eighty-one mothers agreed to participate in the study.
      The Chinese version of the MAI (CMAI) was developed in five stages: translation,
      review, back-translation, a review by a panel of specialists and a pilot test.
      Regarding the reliability of the CMAI, a test of correlations between the
      subscales and the entire scale was performed consecutively. With respect to the
      validity of the MAI, exploratory factor analyses, a test of relationships between
      items and subscales, and an analysis of concurrent criterion-related validity
      were conducted. RESULTS: The CMAI contains four factors in its structure. The
      CMAI and its subscales possess good internal consistency; the Cronbach's alpha
      coefficient was 0.94. In addition, the Pearson product-moment correlation
      coefficient between the CMAI and the Maternal-Fetal Attachment Inventory (MFAI)
      and between the CMAI and the Maternal-Infant Attachment Inventory (MIAI) was 0.38
      and 0.5, respectively. This suggests significant medium and high respective
      correlations between the CMAI and these two scales. One major limitation of this
      study is that participants were recruited from two clinics located in central
      Taiwan. CONCLUSIONS: The CMAI possesses acceptable reliability and validity for
      use in measuring the levels of attachment and affectional ties between mothers
      and their infants. RELEVANCE TO CLINICAL PRACTICE: The CMAI provides further
      evidence of the applicability of the CMAI in clinical maternity care services.

PMID- 23551493
TI  - Minimal important differences in the EORTC QLQ-C15-PAL to determine meaningful
      change in palliative advanced cancer patients.
AB  - AIMS: Quality of life (QOL) is important for advanced cancer patients. Brief
      questionnaires are advantageous to reduce patient burden. In large clinical
      trials, statistically significant small changes can be achieved; however, whether
      such change is clinically relevant is unknown. The purpose of this study was to
      determine the minimal important differences (MID) of the European Organisation
      for Research and Treatment of Cancer quality of life core 15 palliative
      questionnaire (EORTC QLQ-C15-PAL). METHODS: Patients undergoing palliative
      radiotherapy completed the EORTC QLQ-C15-PAL at baseline and 1 month later.
      Anchor and distribution-based assessments were employed to determine the MID
      associated with this instrument. The anchor of overall QOL was used to determine
      meaningful change. RESULTS: In all, 276 patients were included in MID
      calculation. Mean age was 65 years and primary lung, breast or prostate cancers
      were most common. Statistically significant MID for improvement was seen in
      emotional functioning and pain (20.9 and 15.6, respectively). MID for
      deterioration required a 20.4, 24.5, 17.1 and 23.0 change in physical
      functioning, fatigue, pain and appetite loss, respectively, to constitute
      meaningful change. Distribution-based estimates of MID were closest to the
      standard error of measurement. MID for brain and bone metastases patients yielded
      MID larger than previously determined in the incorporation of all patients.
      CONCLUSION: Meaningful change in the EORTC QLQ-C15-PAL is important for
      clinicians to determine the impact of treatment on the QOL of patients and can
      aid in determining the sample size required for clinical trials. Future studies
      should investigate MID in subgroups using symptom-specific modules.

PMID- 23551494
TI  - Brain malformation with loss of normal FGFR3 expression in thanatophoric
      dysplasia type I.
AB  - Thanatophoric dysplasia is a lethal form of chondrodysplastic dwarfism in which
      the cerebral cortex displays a unique and complex malformation. We report a
      female case of thanatophoric dysplasia type I (TD1) with FGFR3 mutation. In this
      case, fetal ultrasonography at the 18th week of gestation led to a prenatal
      diagnosis of TD1 with characteristic bone features. The subject was stillborn at
      the 21st week of gestation, showing marked shortening of the long bones, small
      thorax and curved short femurs, but without a cloverleaf skull. The temporal lobe
      was enlarged and hyperconvoluted, appearing as broad gyri and deep sulci, which
      were composed of focal polymicrogyria-like shallow sulci and heterotopic
      neuroblastic nests in the intermediate zone and marginal zone. Abundant precursor
      cells, immunoreactive for nestin and Ki-67 were observed with scattered mitoses
      in the thickened inner intermediate and subventricular zones of the temporal and
      occipital lobes. The cytoarchitecture from the entorhinal cortex to Ammon's horn
      was disorganized with leptomeningeal glioneuronal heterotopia, immunoreactive for
      doublecortin and nestin. The expression of FGFR3 was virtually not discernible in
      the temporal and occipital lobes or in the hippocampus. Genetic analysis revealed
      a point mutation at C8526T (R248C) in the exon 7 of FGFR3. This is the first
      report that demonstrates that overproduction of intermediate progenitor cells
      might be induced by FGFR3 mutation in a human TD1 case. 

PMID- 23551496
TI  - Increased lymphocytic infiltration in breast cancer correlated with molecular
      subtypes and HER2 gene amplification.

PMID- 23551495
TI  - Pro-angiogenic potential of human chorion-derived stem cells: in vitro and in
      vivo evaluation.
AB  - Human chorion-derived stem cells (hCDSC) were previously shown to demonstrate
      multipotent properties with promising angiogenic characteristics in monolayer
      cell culture system. In our study, we investigated the angiogenic capability of
      hCDSC in 3-dimensional (3D) in vitro and in vivo angiogenic models for the
      purpose of future application in the treatment of ischaemic diseases. Human CDSC
      were evaluated for angiogenic and endogenic genes expressions by quantitative
      PCR. Growth factors secretions were quantified using ELISA. In vitro and in vivo
      vascular formations were evaluated by histological analysis and confocal
      microscopic imaging. PECAM-1(+) and vWF(+) vascular-like structures were observed
      in both in vitro and in vivo angiogenesis models. High secretions of VEGF and
      bFGF by hCDSC with increased expressions of angiogenic and endogenic genes
      suggested the possible angiogenic promoting mechanisms by hCDSC. The cooperation
      of hCDSC with HUVECS to generate vessel-like structures in our systems is an
      indication that there will be positive interactions of hCDSC with existing
      endothelial cells when injected into ischaemic tissues. Hence, hCDSC is suggested
      as the novel approach in the future treatment of ischaemic diseases.

PMID- 23551497
TI  - Evaluating the effects of anthropogenic stressors on source-sink dynamics in pond
      breeding amphibians.
AB  - Although interwetland dispersal is thought to play an important role in regional
      persistence of pond-breeding amphibians, few researchers have modeled amphibian
      metapopulation or source-sink dynamics. Results of recent modeling studies
      suggest anthropogenic stressors, such as pollution, can negatively affect density
      and population viability of amphibians breeding in isolated wetlands. Presumably
      population declines also result in reduced dispersal to surrounding (often
      uncontaminated) habitats, potentially affecting dynamics of nearby populations.
      We used our data on the effects of mercury (Hg) on the American toad ( Bufo
      americanus) as a case study in modeling the effects of anthropogenic stressors on
      landscape-scale amphibian dynamics. We created a structured metapopulation model
      to investigate regional dynamics of American toads and to evaluate the degree to
      which detrimental effects of Hg contamination on individual populations can
      disrupt interpopulation dynamics. Dispersal from typical American toad
      populations supported nearby populations that would otherwise have been
      extirpated over long time scales. Through support of such sink populations,
      dispersal between wetland-associated subpopulations substantially increased
      overall productivity of wetland networks, but this effect declined with
      increasing interwetland distance and decreasing wetland size. Contamination with
      Hg substantially reduced productivity of wetland-associated subpopulations and
      impaired the ability of populations to support nearby sinks within relevant
      spatial scales. Our results add to the understanding of regional dynamics of pond
      breeding amphibians, the wide-reaching negative effects of environmental
      contaminants, and the potential for restoration or remediation of degraded
      habitats.

PMID- 23551498
TI  - Preimplantation genetic diagnosis, an alternative to conventional prenatal
      diagnosis of the hemoglobinopathies.
AB  - Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) both
      represent highly important reproductive choices for couples with a high risk of
      transmitting a severe disease, such as a severe hemoglobinopathy. Conventional
      PND for hemoglobinopathies based on molecular analysis of trophoblast or
      amniocyte DNA has been applied for around 30 years, but the major disadvantages
      with this approach include 'invasive' fetal sampling, and the potential
      involvement of pregnancy termination when affected. In comparison, the major
      advantage of PGD over conventional PND is that it supports the initiation of
      unaffected pregnancies, avoiding the need to terminate affected pregnancies.
      However, it is a multistep technically demanding procedure requiring the close
      collaboration of experts from several fields. PGD is also limited by the need to
      involve assisted reproduction, even in couples without fertility problems.
      Furthermore, even for fertile couples, pregnancy rates rarely surpass 30-35%.
      Both PND and PGD have advantages and drawbacks. Before embarking on either
      procedure, couples should be carefully counseled by experts so that they can
      select the option most appropriate for them. Finally, whatever their choice, it
      is paramount that both prenatal and PGD be applied with the highest standards of
      clinical, laboratory, and ethical practice. 

PMID- 23551499
TI  - L-amino acid oxidase isolated from Bothrops pirajai induces apoptosis in BCR-ABL
      positive cells and potentiates imatinib mesylate effect.
AB  - Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by
      the presence of Philadelphia chromosome and by BCR-ABL1, which encodes the BCR
      ABL oncoprotein. Although imatinib mesylate (IM) is effective for CML treatment,
      patients in accelerated and blastic phases of the disease are often refractory to
      this therapy, and there are also cases of IM resistance in patients in the
      chronic phase. Therefore, potential new drugs are being investigated to improve
      the efficiency of the therapy of CML such as snake venoms and their compounds. In
      this investigation, Bothrops pirajai L-amino acid oxidase (BpirLAAO-I) effect on
      normal peripheral blood mononuclear cells (PBMC) and on BCR-ABL(+) cell line was
      assessed to explore its potential against leukaemic cells. MTT viability assay,
      lymphocyte subsets quantification and cell activation markers expression were
      performed to evaluate BpirLAAO-I effect on normal PBMC. The effect of BpirLAAO-I
      on HL-60 and HL-60.BCR-ABL cell lines was assessed by apoptosis detection.
      BpirLAAO-I was able to induce apoptosis in HL-60 and HL-60.BCR-ABL cell lines in
      a dose-dependent manner, promoted caspases 3, 8 and 9 activation and enhanced IM
      effect while not affecting the viability of normal cells. In addition, BpirLAAO-I
      promoted immune cells activation and lymphocytes subsets changes on normal PBMC.
      The results indicate that BpirLAAO-I induces apoptosis and potentiates IM effect
      on BCR-ABL(+) cells. 

PMID- 23551500
TI  - Outcomes of transperineal template-guided prostate biopsy in 409 patients.
AB  - OBJECTIVE: To present the template-guided transperineal prostate biopsy (TPB)
      outcomes for patients of two urologists from a single institution. PATIENTS AND
      METHODS: We conducted a prospective study of 409 consecutive men who underwent
      TPB between December 2006 and June 2008 in a tertiary referral centre using a
      standardized 14-region technique. The procedure was performed as day surgery
      under general anaesthesia with fluoroquinolone antibiotic cover. Follow-up took
      place within 2 weeks, during which time men were interviewed using a standardized
      template. Results were compared with those of the Australian national prostate
      biopsy audits performed by the Urological Society of Australia and New Zealand
      (USANZ). RESULTS: Indications for biopsy included elevated prostate-specific
      antigen (PSA) level (75%), with a median PSA level of 6.5 ng/mL, abnormal digital
      rectal examination (8%) and active surveillance (AS) re-staging (18%). The mean
      patient age was 63 years and two-thirds of patients were undergoing their first
      biopsy. A positive biopsy was found in 232 men, 74% of whom had a Gleason score
      of >=7. The overall cancer detection rate was 56.7% (USANZ 2005 national audit =
      56.5%). Stratified between those having their first TPB or a repeat procedure
      (after a previous negative biopsy), the detection rates were 64.4 and 35.6%,
      respectively. Significantly higher detection rates were found in prostates <50 mL
      in volume than in larger prostates (65.2 vs 38.3%, respectively, P < 0.001).
      Haematuria was the most common side effect (51.7%). Others included dysuria
      (16.4%), acute urinary retention (4.2%) and fever (3.2%). One patient (0.2%) had
      septicaemia requiring i.v. antibiotics. Repeat biopsy was not associated with
      increased complication rates. CONCLUSIONS: TPB is a safe and efficacious
      technique, with a cancer detection rate of 56.7% in the present series, and a low
      incidence of major side effects. Stratified by prostate volume, the detection
      rate of TPB was higher in smaller glands. Given the relatively low rate of
      serious complications, clinicians could consider increasing the number of TPB
      biopsy cores in larger prostates as a strategy to improve cancer detection within
      this group. Conversely, in patients on AS programmes, a staging TPB may be a
      superior approach for patients undergoing repeat biopsy so as to minimize their
      risk of serious infection.

PMID- 23551501
TI  - Camelina seed transcriptome: a tool for meal and oil improvement and
      translational research.
AB  - Camelina (Camelina sativa), a Brassicaceae oilseed, has received recent interest
      as a biofuel crop and production platform for industrial oils. Limiting wider
      production of camelina for these uses is the need to improve the quality and
      content of the seed protein-rich meal and oil, which is enriched in oxidatively
      unstable polyunsaturated fatty acids that are deleterious for biodiesel. To
      identify candidate genes for meal and oil quality improvement, a transcriptome
      reference was built from 2047 Sanger ESTs and more than 2 million 454-derived
      sequence reads, representing genes expressed in developing camelina seeds. The
      transcriptome of approximately 60K transcripts from 22 597 putative genes
      includes camelina homologues of nearly all known seed-expressed genes, suggesting
      a high level of completeness and usefulness of the reference. These sequences
      included candidates for 12S (cruciferins) and 2S (napins) seed storage proteins
      (SSPs) and nearly all known lipid genes, which have been compiled into an
      accessible database. To demonstrate the utility of the transcriptome for seed
      quality modification, seed-specific RNAi lines deficient in napins were generated
      by targeting 2S SSP genes, and high oleic acid oil lines were obtained by
      targeting FATTY ACID DESATURASE 2 (FAD2) and FATTY ACID ELONGASE 1 (FAE1). The
      high sequence identity between Arabidopsis thaliana and camelina genes was also
      exploited to engineer high oleic lines by RNAi with Arabidopsis FAD2 and FAE1
      sequences. It is expected that these transcriptomic data will be useful for
      breeding and engineering of additional camelina seed traits and for translating
      findings from the model Arabidopsis to an oilseed crop. 

PMID- 23551502
TI  - Neuromodulation of emotion using functional electrical stimulation applied to
      facial muscles.
AB  - BACKGROUND AND OBJECTIVE: Major depressive disorder (MDD) is a common condition
      for which available pharmaceutical treatments are not always effective and can
      have side-effects. Therefore, alternative and/or complementary MDD treatments are
      needed. Research on facial expressions has shown that facial movements can induce
      the corresponding emotions, particularly when specific attention is paid to
      voluntarily activating muscles that are typically only activated involuntarily
      while expressing emotions. We hypothesized that functional electrical stimulation
      (FES) applied to facial muscles may enhance this effect due to its ability to
      modulate central nervous system plasticity. Thus, applying FES to the facial
      muscles associated with smiling (including the "Duchenne marker") may increase
      the activity of subcortical nuclei related to positive emotions and counteract
      symptoms of depression. METHODS: Twelve able-bodied subjects received FES and
      were compared with a group of 12 control subjects. Both groups underwent the same
      experimental procedures involving a cognitive task, and a deception was used such
      that subjects were unaware that the objective was to modulate mood. Assessments
      with the Positive and Negative Affect Schedule-Expanded Form (PANAS-X) were
      administered before and after the experiment. RESULTS: No significant between
      group differences were found in the change scores for our primary outcomes, the
      PANAS-X item "happy," and aggregate scores "Joviality" and "Positive Affect."
      Significant differences were, however, detected for secondary outcomes
      "determined," "daring," "scared," and "concentrating." CONCLUSIONS: These results
      suggest that modulating emotion using FES may be possible, but is difficult to
      target accurately. Further work is warranted to explore FES applications to MDD.

PMID- 23551503
TI  - Donor-specific antibodies: can they predict C4d deposition in pediatric heart
      recipients?
AB  - There is limited evidence regarding the utility of circulating DSA in
      surveillance for AMR of pediatric heart recipients. Our hypothesis is that
      quantitation of DSA improves their power for predicting a C4d+, an integral
      component in the current diagnostic criteria of AMR. All pediatric recipients
      transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA
      determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining
      by immunohistochemical methods. A total of 183 paired DSA-EMB determinations were
      identified in 60 patients, a median of three paired studies per patient (range: 1
      9). DSA were detected in 60 of these determinations. A receiver-operating
      characteristic plot identified a threshold single-antibody MFI of >6000 that
      strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value
      (0.97) and specificity (0.95). The sensitivity and positive predictive values
      were 0.71 and 0.60, respectively. The predictive power of single-antigen DSA for
      C4d deposition was improved in pediatric heart recipients using an institution
      specific MFI threshold value. In post-transplant care, quantitative DSA should be
      an essential component in the surveillance for AMR. 

PMID- 23551504
TI  - Prolonged stimuli alter the bacterial chemosensory clusters.
AB  - The clustering of membrane-bound receptors plays an essential role in various
      biological systems. A notable model system for studying this phenomenon is the
      bacterial chemosensory cluster that allows motile bacteria to navigate along
      chemical gradients in their environment. While the basic structure of these
      chemosensory clusters is becoming clear, their dynamic nature and operation are
      not yet understood. By measuring the fluorescence polarization of tagged receptor
      clusters in live Escherichia coli cells, we provide evidence for stimulus-induced
      dynamics in these sensory clusters. We find that when a stimulus is applied, the
      packing of the receptors slowly decreases and that the process reverses when the
      stimulus is removed. Consistent with these physical changes we find that the
      effective cooperativity of the kinase response slowly evolves in the presence of
      a stimulus. Time-lapse fluorescence imaging indicates that, despite these
      changes, the receptor clusters do not generally dissociate upon ligand binding.
      These data reveal stimulus-dependent plasticity in chemoreceptor clusters.

PMID- 23551506
TI  - Apical resorption in teeth with periapical lesions: correlation between
      radiographic diagnosis and SEM examination.
AB  - This study correlated the radiographic findings and scanning electron microscopy
      (SEM) images of external apical resorption (EAR) in teeth with periapical
      lesions. Standard radiographs were taken from 45 teeth with periapical lesions
      before their extraction. Using a radiographic examination, the root apex of each
      tooth was classified according to the EAR into the following categories:
      radiographic external apical resorption (REAR) absent, superficial and deep. The
      apical root surface was also examined with SEM. Photomicrographs of EARs were
      classified as periforaminal (PEAR) and foraminal (FEAR) in three degrees: 0, 1
      and 2. REAR was present in 72.5% of cases, of which 20% were deep. Based upon SEM
      analysis, PEAR and FEAR occurred in 75.6% and 66.7% of cases respectively; 51.2%
      and 59% respectively, of these teeth received a score of 2. Only 15.4% of the
      specimens were unaffected by EAR. When teeth with periapical lesions were
      examined for EAR with both radiography and by SEM, there was no correlation
      between the findings.

PMID- 23551507
TI  - Evaluation of microleakage of root canal fillings irradiated with different
      output powers of erbium, chromium:yttrium-scandium-gallium-garnet laser.
AB  - This study evaluated the root canal seal achieved by irradiation with an erbium,
      chromium:yttrium-scandium-gallium-garnet laser, and the optimal output power to
      remove debris and the smear layer were determined. One hundred mandibular
      premolar teeth were prepared and divided into four groups. Group 1 was not lased
      but was irrigated with 5 mL of 5.25% NaOCl and 5 mL of 17%
      ethylenediaminetetraacetic acid. Group 2 was irradiated at a panel setting of 1
      W, group 3 at 2 W and group 4 at 2.5 W, with a 50% water level and 48% air
      cooling level. Root canals were obturated by cold lateral compaction, and apical
      microleakage was measured using a fluid filtration model. The remaining debris
      and smear layer were evaluated via scanning electron microscopy. Statistically
      significant differences were detected between groups. Irradiation at 1 and 2 W
      using an erbium, chromium:yttrium-scandium-gallium-garnet laser produced a seal
      superior to that of the other treatments.

PMID- 23551508
TI  - Evaluation of the antimicrobial activities of chlorhexidine gluconate, sodium
      hypochlorite and octenidine hydrochloride in vitro.
AB  - The objective of this study was to compare the antimicrobial activity of sodium
      hypochlorite (NaOCl), chlorhexidine gluconate (CHX) and octenidine hydrochloride
      (OCT) in different concentrations against endodontic pathogens in vitro. Agar
      diffusion procedure was used to determine the antimicrobial activity of the
      tested materials. Enterococcus faecalis, Candida albicans and the mixture of
      these were used for this study. In the agar diffusion test, 5.25% NaOCl exhibited
      better antimicrobial effect than the other concentrations of NaOCl for all
      strains. All concentrations of OCT were effective against C. albicans and E.
      faecalis. Some 0.2% CHX was ineffective on all microorganisms. Antibacterial
      effectiveness of all experimental solutions decreased on the mixture of all
      strains. Decreasing concentrations of NaOCl resulted in significantly reduced
      antimicrobial effect.

PMID- 23551509
TI  - Effect of post-space treatments on the push-out bond strength and failure modes
      of glass fibre posts.
AB  - The aim of this study was to evaluate the effect of different post-space
      treatments on the push-out bond strength and failure modes of glass fibre posts.
      Forty mandibular premolar roots were cut and endodontically treated. Post spaces
      were prepared and roots were divided into four groups. In group 1 distilled water
      irrigation (control), in group 2 2.25% NaOCl irrigation, in group 3 2.25% NaOCl +
      17% EDTA irrigation were done and in group 4 diode laser was applied to the
      prepared post spaces. Scanning electron microscope (SEM) analysis was made for
      each group. Fibre posts were then luted with resin cement. Each root was prepared
      for push-out test. Data were statistically analysed with anova (P = 0.05). After
      push-out test, the failure modes were observed but not statistically analysed.
      There were statistically significant differences between Group 3 and Group 2 in
      both regions (P < 0.05), also in the middle region of Group 4 and Group 2 (P <
      0.05). Cervical root segments showed higher bond strengths than middle ones in
      all groups (P < 0.05). The highest bond strength values were obtained from
      NaOCl/EDTA and the lowest bond strength values were obtained from NaOCl for both
      regions.

PMID- 23551510
TI  - Comparison of the centring ability of the ProTaperTM and ProTaper UniversalTM
      rotary systems for preparing curved root canals.
AB  - The aim of this in vitro study was to compare the centring ability of the
      ProTaperTM and ProTaper UniversalTM rotary systems for preparing curved root
      canals, by means of preoperative and postoperative imaging of a cross-section of
      their coronal, middle and apical thirds. Twenty mesiobuccal root canals of human
      mandibular first molars with a degree of curvature ranging from 55 degrees  to 60
      degrees  were randomly divided into two groups of 10 specimens each: Group 1,
      ProTaperTM rotary system; and Group 2, ProTaper UniversalTM rotary system. The
      data were analysed statistically by Kruskal-Wallis and Student's t-test at the 5%
      significance level. The results showed that the differences between the
      percentages of the presence of deviation observed were not statistically
      significant. Both systems showed the capacity for producing centred preparations
      in curved root canals with low proportions of deviation.

PMID- 23551511
TI  - Evaluation of the antifungal activity of four solutions used as a final rinse in
      vitro.
AB  - The aim of the study was to compare the antifungal activity of 1.3% sodium
      hypochlorite (NaOCl), 2% chlorhexidine (CHX), MTAD and Tetraclean as a final
      rinse against Candida albicans in a human tooth model in vitro. Ninety extracted
      human maxillary central and lateral incisor teeth were randomly divided into four
      groups each with 20 teeth, a positive and a negative control each with five
      teeth. After preparing the root canals, teeth were inoculated with Candida
      albicans (ATCC 10261) and incubated for 72 h. Teeth were divided into four
      experimental groups according to the irrigation solution as follows: NaOCl, CHX,
      MTAD and Tetraclean. After culturing aliquots from the experimental teeth on
      Sabouraud 4% dextrose agar, colony-forming units were counted. The results showed
      that 1.3% NaOCl and 2% CHX were equally effective and significantly superior to
      MTAD and Tetraclean (P < 0.05). Furthermore, antifungal efficacy of Tetraclean
      was significantly superior to MTAD (P < 0.05).

PMID- 23551512
TI  - The importance of soft tissue examination in post-traumatic decision-making: a
      case report.
AB  - Dental and facial traumas involving teeth and supporting tissues are common
      sports-related injuries. In this case report treatment of a 23-year-old student
      who had been elbowed by an opponent player during a basketball game, which caused
      oblique fractures on both maxillary incisor teeth is presented. The patient
      presented 17 days following trauma having completed full recovery of soft
      tissues. A fragment of upper incisor tooth had been embedded in lower lip at the
      time of trauma, which was covered by healing tissues. At the 1 month control the
      patient complained of a hard structure in his lower lip. The elusive broken
      fragment was revealed by a radiograph and then removed surgically. This case
      report is a good example of the importance of the training of general dentists
      about sports-related traumatic injuries as well as emphasising the importance of
      the use of mouthguards during contact sports.

PMID- 23551515
TI  - 'Vaping' profiles and preferences: an online survey of electronic cigarette
      users.
AB  - AIMS: To characterize e-cigarette use, users and effects in a sample of
      Electronic Cigarette Company (TECC) and Totally Wicked E-Liquid (TWEL) users.
      DESIGN AND SETTING: Online survey hosted at the University of East London with
      links from TECC/TWEL websites from September 2011 to May 2012. MEASUREMENTS:
      Online questionnaire. PARTICIPANTS: One thousand three hundred and forty-seven
      respondents from 33 countries (72% European), mean age 43 years, 70% male, 96%
      Causasian, 44% educated to degree level or above. FINDINGS: Seventy-four percent
      of participants reported not smoking for at least a few weeks since using the e
      cigarette and 70% reported reduced urge to smoke. Seventy-two percent of
      participants used a 'tank' system, most commonly, the eGo-C (23%). Mean duration
      of use was 10 months. Only 1% reported exclusive use of non-nicotine (0 mg)
      containing liquid. E-cigarettes were generally considered to be satisfying to
      use; elicit few side effects; be healthier than smoking; improve cough/breathing;
      and be associated with low levels of craving. Among ex-smokers, 'time to first
      vape' was significantly longer than 'time to first cigarette' (t1104  = 11.16, P
      < 0.001) suggesting a lower level of dependence to e-cigarettes. Ex-smokers
      reported significantly greater reduction in craving than current smokers (chi(2)
      1  = 133.66, P < 0.0007) although few other differences emerged between these
      groups. Compared with males, females opted more for chocolate/sweet flavours
      (chi(2) 1  = 16.16, P < 0.001) and liked the e-cigarette because it resembles a
      cigarette (chi(2) 3  = 42.65, P < 0.001). CONCLUSIONS: E-cigarettes are used
      primarily for smoking cessation, but for a longer duration than nicotine
      replacement therapy, and users believe them to be safer than smoking.

PMID- 23551516
TI  - How mechanical stress controls microtubule behavior and morphogenesis in plants:
      history, experiments and revisited theories.
AB  - Microtubules have a key role in plant morphogenesis, as they control the oriented
      deposition of cellulose in the cell wall, and thus growth anisotropy. The idea
      that mechanical stress could be one of the main determinants behind the
      orientation of microtubules in plant cells emerged very soon after their
      discovery. The cause of mechanical stress in plant cells is turgor pressure,
      which can build up to 1 MPa and is restrained by cell wall stiffness. On the
      tissue scale, this can lead to regional patterns of tension, in particular in the
      epidermis of aerial organs, which resist the stress generated by cells in
      internal tissues. Here we summarize more than 50 years of work on the
      contribution of mechanical stress in guiding microtubule behavior, and the
      resulting impact on growth anisotropy and growth heterogeneity. We propose a
      conceptual model on microtubule dynamics and their ability to self-organize in
      bundles parallel to the direction of maximal stress, as well as a synthetic
      representation of the putative mechanotransducers at play.

PMID- 23551517
TI  - Rates of visual field loss before and after trabeculectomy.
AB  - PURPOSE: To compare the rates of change in the visual field (VF) in patients with
      glaucoma before and after trabeculectomy. METHODS: Of 52 eyes of 52 patients with
      different types of chronic glaucoma who underwent first trabeculectomy were
      evaluated retrospectively. Pre- and postoperative-automated visual fields
      measured by the same technique were compared to detect differences in rates of
      change. Rates of VF loss before and after trabeculectomy were calculated using
      mean deviation (MD). Linear mixed models were used to compare the rates of change
      in the VF before and after trabeculectomy. RESULTS: The mean follow-up period pre
      and post-trabeculectomy was 3.9 years (min 0.9, max 10.7) and 3.8 years (min
      2.0, max 8.0), respectively. The intraocular pressure (IOP) decreased from 18.1
      mmHg (SD = 4.7) before trabeculectomy to 11.1 mmHg (SD = 2.9) at the last follow
      up after trabeculectomy. The rate of MD loss was reduced with 56% on average,
      from -0.36 dB/year before surgery to -0.16 dB/year after surgery (p = 0.15).
      CONCLUSION: Trabeculectomy considerably decreased the rates of change in the
      glaucomatous visual field.

PMID- 23551518
TI  - Safety of lumbar puncture in patients with cerebral venous thrombosis.
AB  - BACKGROUND AND PURPOSE: Lumbar puncture (LP) may precipitate cerebral venous
      thrombosis (CVT), but it is unclear if LP is deleterious in patients with CVT. We
      aimed to assess the safety of LP in the International Study on Cerebral Veins and
      Dural Sinus Thrombosis prospective cohort. METHODS: In 624 patients with CVT, we
      compared the prognosis of patients submitted or not to LP. The primary outcome
      was 'death or dependency at 6 months', as evaluated by the modified Rankin Scale
      (mRS; mRS = 3-6, with adjustment for variables associated with poor prognosis);
      secondary outcomes were: 'worsening after admission'; 'acute death'; and
      'complete recovery at 6 months' (mRS = 0-1). We analyzed the same outcomes in
      subgroups of patients with brain lesions on the admission computer
      tomography/magnetic resonance imaging. RESULTS: LP was performed in 224 patients
      (35.9%). There was no difference in frequency of 'death or dependency at 6
      months' between patients with or without LP [13.4% vs. 14.4%; odds ratio (OR) =
      0.9, 95% confidence interval (CI) 0.6-1.5; P = 0.739]. LP was not associated with
      'worsening after hospitalization' [21.5% vs. 23.5%; OR = 0.9, 95% CI 0.6-1.3; P =
      0.577], 'acute death' [3.6% vs. 3.3%; OR = 1.1, 95% CI 0.5-2.7; P = 0.844] or
      'complete recovery' [79.9% vs. 76.6%; OR = 1.2, 95% CI 0.8-1.7; P = 0.484]. In
      the subgroups of patients with brain lesions, the prognoses were not different
      between patients submitted or not to LP. CONCLUSION: LP was not associated with
      the functional outcome of patients with CVT, suggesting that LP was not harmful
      in these patients. These results should not be generalized to patients with large
      brain lesions and risk of herniation where LP is contraindicated.

PMID- 23551519
TI  - Characteristics of atrial fibrillation and comorbidities in familial atrial
      fibrillation.
AB  - INTRODUCTION: One-third of lone atrial fibrillation (AF) presents as familial
      disorder. Heterogeneity of both genetic background and clinical manifestations
      remains largely uncharacterized. We aimed to evaluate the clinical
      characteristics and especially the triggering factors of familial AF. METHODS AND
      RESULTS: Probands were screened from 84 consecutive lone AF patients seen in our
      tertiary hospital arrhythmia clinic. Those confirmed to have at least 1 first
      degree relative with lone AF were included. 12-lead ECG, Holter recording, and
      cardiac ultrasound were performed. Data concerning arrhythmias and other medical
      history were collected. Altogether 17 kindreds with 59 AF patients, 52 of whom
      had lone AF, were identified. Initiation of AF was atrial extrasystolia (PACs)
      related in 35%, and vagal or sympathetic in 30% of cases. Within any given
      family, the characteristics related to AF initiation were the same in two-thirds
      of kindreds. AV conduction abnormalities were found in 2 families, sinus node
      dysfunction in 2 families, and both in 3 families. Frequent premature ventricular
      complexes (>1,000/24 hours) were observed in 9 families. Additional comorbidities
      included dilative cardiomyopathy and sudden death in 3 families. CONCLUSIONS: In
      familial AF the proportion of PACs-related AF is lower than expected. The
      arrhythmia triggers for lone AF in general are heterogeneous but often family
      specific. Concomitant rhythm disorders, as well as cardiomyopathies, are common
      in patients with familial AF. A positive family history for AF in an apparently
      lone AF patient may be a marker for wider spectrum of cardiac pathology.

PMID- 23551520
TI  - Emodin improves lipopolysaccharide-induced microcirculatory disturbance in rat
      mesentery.
AB  - OBJECTIVE: Sepsis is a systemic inflammatory response syndrome. Emodin is a major
      ingredient of Rheum Palmatum, a Chinese herb that is widely used in China for
      treatment of endotoxemia-related diseases. This study intended to examine the
      effect of Emodin on LPS-induced rat mesenteric microcirculatory disturbance and
      the underlying mechanisms. METHODS: The male Wistar rats received LPS (5
      mg/kg/hr) for 90 min, with or without administration of Emodin (10 mg/kg/hr) by
      enema 30 min before (pre-treatment) or after (post-treatment) LPS infusion, and
      the dynamics of mesenteric microcirculation were determined by inverted
      intravital microscopy. Expression of adhesion molecules and TLR4, NF-kappaB p65,
      ICAM-1, MPO, and AP-1 in mesentery tissue was evaluated by flow cytometry and
      Western-blot, respectively. RESULTS: Pre or post-treatment with Emodin
      significantly ameliorated LPS-induced leukocyte emigration, reactive oxygen
      species production and albumin leakage, and the expression of TLR4, NF-kappaB
      p65, ICAM-1, MPO and AP-1 in mesentery. CONCLUSIONS: These results demonstrate
      the beneficial role of Emodin in attenuating the LPS-induced microcirculatory
      disturbance, and support the use of Emodin for patients with endotoxemia.

PMID- 23551521
TI  - Ectopic lipid storage and insulin resistance: a harmful relationship.
AB  - Obesity increases the risk of metabolic diseases, including insulin resistance
      and type 2 diabetes, as well as cardiovascular disease. In addition to lipid
      accumulation in adipose tissue, obesity is associated with increased lipid
      storage in ectopic tissues, such as skeletal muscle and liver. Furthermore, lipid
      accumulation in the heart may result in cardiac dysfunction and heart failure. It
      has recently been demonstrated that intracellular lipid accumulation in ectopic
      tissues leads to pathological responses and impaired insulin signalling. Here, we
      will review the current understanding of how lipid storage and lipid droplet
      physiology affect the risk of developing metabolic diseases.

PMID- 23551524
TI  - Effect of a disinfection strategy on the methicillin-resistant Staphylococcus
      aureus CC398 prevalence of sows, their piglets and the barn environment.
AB  - AIMS: To assess, in a cleaned and disinfected barn environment, the efficacy of
      an animal disinfection strategy to reduce the livestock-associated methicillin
      resistant Staphylococcus aureus (LA-MRSA) prevalence in sows, their offspring and
      the barn environment. METHODS AND RESULTS: On each farm, six sow rounds were
      sampled; sows were divided into either a test or control group. Per round, 20
      sows and 40 of their piglets were sampled at different time points together with
      the barn environment. The disinfection strategy of the test groups consisted of
      washing the sows with a shampoo followed by disinfection of the skin with a
      solution containing chlorhexidine digluconate and isopropanol. On the first day
      of disinfection and 6 days after stopping the disinfection, a significant
      decrease (P < 0.01) of on average 68 and 66% in sow MRSA prevalence was observed
      on both farms, whereas no decrease was seen in the control groups. Just before
      weaning, 21-28 days after the end of the disinfection strategy, the difference in
      MRSA prevalence between both groups was reduced to 4% and no longer significant
      (P = 0.20). The MRSA prevalence of the piglets in the test groups was
      significantly lower (26%; P < 0.01) 6 days after the end of disinfection. Just
      before weaning, this difference was reduced to 5% but still significant (P <
      0.01). In the swine nursery unit, no significant difference (P = 0.99) was seen
      between both groups. Based on semi-quantitative counts, a relationship (r(2)  >
      0.6; P < 0.01) was seen between MRSA contamination in the barn environment and
      the MRSA prevalence in pigs. CONCLUSION: Results show that the tested
      disinfection strategy reduces temporarily the sow and piglet MRSA status, but
      does not result in a final reduction in MRSA at weaning or in the nursery unit.
      SIGNIFICANCE AND IMPACT OF THE STUDY: First report on the efficacy of an animal
      disinfection strategy to reduce LA-MRSA prevalence in sows, their offspring and
      the barn environment.

PMID- 23551525
TI  - Effects of dam-induced landscape fragmentation on amazonian ant-plant mutualistic
      networks.
AB  - Mutualistic networks are critical to biological diversity maintenance; however,
      their structures and functionality may be threatened by a swiftly changing world.
      In the Amazon, the increasing number of dams poses a large threat to biological
      diversity because they greatly alter and fragment the surrounding landscape.
      Tight coevolutionary interactions typical of tropical forests, such as the ant
      myrmecophyte mutualism, where the myrmecophyte plants provide domatia nesting
      space to their symbiotic ants, may be jeopardized by the landscape changes caused
      by dams. We analyzed 31 ant-myrmecophyte mutualistic networks in undisturbed and
      disturbed sites surrounding Balbina, the largest Central Amazonian dam. We tested
      how ant-myrmecophyte networks differ among dam-induced islands, lake edges, and
      undisturbed forests in terms of species richness, composition, structure, and
      robustness (number of species remaining in the network after partner
      extinctions). We also tested how landscape configuration in terms of area,
      isolation, shape, and neighborhood alters the structure of the ant-myrmecophyte
      networks on islands. Ant-myrmecophytic networks were highly compartmentalized in
      undisturbed forests, and the compartments had few strongly connected mutualistic
      partners. In contrast, networks at lake edges and on islands were not
      compartmentalized and were negatively affected by island area and isolation in
      terms of species richness, density, and composition. Habitat loss and
      fragmentation led to coextinction cascades that contributed to the elimination of
      entire ant-plant compartments. Furthermore, many myrmecophytic plants in
      disturbed sites lost their mutualistic ant partners or were colonized by
      opportunistic, nonspecialized ants. Robustness of ant-myrmecophyte networks on
      islands was lower than robustness near lake edges and in undisturbed forest and
      was particularly susceptible to the extinction of plants. Beyond the immediate
      habitat loss caused by the building of large dams in Amazonia, persistent edge
      effects and habitat fragmentation associated with dams had large negative effects
      on animal-plant mutualistic networks.

PMID- 23551526
TI  - Developing complex interventions for nursing: a critical review of key
      guidelines.
AB  - AIMS AND OBJECTIVES: To identify the most comprehensive approach to developing
      complex interventions for nursing research and practice. BACKGROUND: The majority
      of research in nursing is descriptive and exploratory in nature. There is an
      increasing professional and political demand for nurses to develop and provide
      evidence to support their practices. Nurses need to explore current practice and
      develop and test interventions to provide the evidence required for safe
      practice. DESIGN: A literature review using a systematic approach. METHODS: The
      review was carried out using four databases: CINAHL, PubMed, PsycINFO and BNI
      (2000-2011), and the search was limited to 'brief interventions' and complex
      intervention development (January 2000-September 2011). Included papers reported
      on guidelines for intervention development or 'how' an intervention was
      developed. RESULTS: Six papers reported on guidelines for developing
      interventions. There are many similarities between the guidelines with a similar
      pattern of guideline development in Europe and the USA. The only guideline
      reported to have been used in the development of interventions is the Medical
      Research Council framework (MRC) (A Framework for Developing and Evaluation of
      RCTs for Complex Interventions to Improve Health, 2000), with 9 of 14 papers that
      describe the development of an intervention reporting the use of this guideline.
      The other five papers did not mention the use of any guideline or framework.
      CONCLUSIONS: The MRC (A Framework for Developing and Evaluation of RCTs for
      Complex Interventions to Improve Health, 2000) framework appears to be the most
      widely used guideline reported for developing complex interventions. Although the
      updated MRC (Developing and Evaluating Complex Interventions, 2008) framework
      adds considerably to the original MRC (A Framework for Developing and Evaluation
      of RCTs for Complex Interventions to Improve Health, 2000) framework, other
      guidelines contribute additional guidance which can inform the development of
      nursing interventions. These additional guidelines are presented in a model for
      developing complex interventions for nursing. RELEVANCE TO CLINICAL PRACTICE: The
      model will help nurses planning to develop nursing interventions as it provides
      additional and nursing-specific guidance to the MRC (Developing and Evaluating
      Complex Interventions, 2008) framework for the development of complex
      interventions for nursing practice.

PMID- 23551527
TI  - Sequential healing of open extraction sockets. An experimental study in monkeys.
AB  - AIM: To describe the sequential healing of open extraction sockets at which no
      attempts to obtain a primary closure of the coronal access to the alveolus have
      been made. MATERIAL AND METHODS: The third mandibular premolar was extracted
      bilaterally in 12 monkeys, and no sutures were applied to close the wound. The
      healing after 4, 10, 20, 30, 90 and 180 days was morphometrically studied.
      RESULTS: After 4 days of healing, a blood clot mainly occupied the extraction
      sockets, with the presence of an inflammatory cells' infiltrate. A void was
      confined in the central zones of the coronal and middle regions, in continuity
      with the entrance of the alveoli. At 10 days, the alveolus was occupied by a
      provisional matrix, with new bone formation lining the socket bony walls. At 20
      days, the amount of woven bone was sensibly increasing. At 30 days, the alveolar
      socket was mainly occupied by mineralized immature bone at different stages of
      healing. At 90 and 180 days, the amount of mineralized bone decreased and
      substituted by trabecular bone and bone marrow. Bundle bone decreased from 95.5%
      at 4 days to 7.6% at 180 days, of the whole length of the inner alveolar surface.
      CONCLUSIONS: Modeling processes start from the lateral and apical walls of the
      alveolus, leading to the closure of the socket with newly formed bone within a
      month from extraction. Remodeling processes will follow the previous stages,
      resulting in trabecular and bone marrow formation and in a corticalization of the
      socket access.

PMID- 23551529
TI  - Phylogeny and biogeography of an uncultured clade of snow chytrids.
AB  - Numerous studies have shown that snow can contain a diverse array of algae known
      as 'snow algae'. Some reports also indicate that parasites of algae (e.g.
      chytrids) are also found in snow, but efforts to phylogenetically identify 'snow
      chytrids' have not been successful. We used culture-independent molecular
      approaches to phylogenetically identify chytrids that are common in long-lived
      snowpacks of Colorado and Europe. The most remarkable finding of the present
      study was the discovery of a new clade of chytrids that has representatives in
      snowpacks of Colorado and Switzerland and cold sites in Nepal and France, but no
      representatives from warmer ecosystems. This new clade ('Snow Clade 1' or SC1) is
      as deeply divergent as its sister clade, the Lobulomycetales, and phylotypes of
      SC1 show significant (P < 0.003) genetic-isolation by geographic distance
      patterns, perhaps indicating a long evolutionary history in the cryosphere. In
      addition to SC1, other snow chytrids were phylogenetically shown to be in the
      order Rhizophydiales, a group with known algal parasites and saprotrophs. We
      suggest that these newly discovered snow chytrids are important components of
      snow ecosystems where they contribute to snow food-web dynamics and the release
      of nutrients due to their parasitic and saprotrophic activities.

PMID- 23551528
TI  - Mechanotransduction at focal adhesions: integrating cytoskeletal mechanics in
      migrating cells.
AB  - Focal adhesions (FAs) are complex plasma membrane-associated macromolecular
      assemblies that serve to physically connect the actin cytoskeleton to integrins
      that engage with the surrounding extracellular matrix (ECM). FAs undergo
      maturation wherein they grow and change composition differentially to provide
      traction and to transduce the signals that drive cell migration, which is crucial
      to various biological processes, including development, wound healing and cancer
      metastasis. FA-related signalling networks dynamically modulate the strength of
      the linkage between integrin and actin and control the organization of the actin
      cytoskeleton. In this review, we have summarized a number of recent
      investigations exploring how FA composition is affected by the mechanical forces
      that transduce signalling networks to modulate cellular function and drive cell
      migration. Understanding the fundamental mechanisms of how force governs adhesion
      signalling provides insights that will allow the manipulation of cell migration
      and help to control migration-related human diseases.

PMID- 23551530
TI  - Minimal important differences in the EORTC QLQ-C30 in patients with advanced
      cancer.
AB  - AIMS: Quality of life (QOL) is important in patients with advanced cancer. The
      European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a
      general QOL tool used in cancer patients. Often, with a large enough sample,
      statistical significance of changecan be reached, however the clinical
      significance is often unknown. This study aimed to determine the magnitude of
      change that is meaningful to advanced cancer patients in the EORTC QLQ-C30.
      METHODS: Patients completed the EORTC QLQ-C30 at baseline and 1 month post
      radiation to assess changes in their QOL. Minimal important differences (MID)
      were calculated through anchor and distribution-based methods for improvement and
      deterioration. The two anchors of overall health and overall QOL were used to
      determine meaningful change. RESULTS: Statistically significant meaningful
      changes were seen in the use of both anchors. The overall health anchor produced
      a greater number of scales and symptoms that reached a statistically significant
      meaningful change. Meaningful change for improvement with these two anchors
      ranged from 9.1 units (cognitive functioning) to 23.5 units (pain), and for
      deterioration it ranged from 7.2 units (physical functioning) to 13.5 units (role
      functioning). Distribution-based estimates were closest to 0.5 SD. CONCLUSION:
      Knowledge of meaningful change on the EORTC QLQ-C30 allows physicians to assess
      patients' changes over time, along with evaluating the impact of treatment on a
      patient's QOL. This knowledge gives insight into whether the treatment is
      effective and, ultimately, whether it should be continued. Knowledge of MID may
      assist in the determination of sample size for future trials.

PMID- 23551531
TI  - Single and repeated sevoflurane or desflurane exposure does not impair spatial
      memory performance of young adult mice.
AB  - Volatile anesthetics are known to disturb the spatial memory in aged rodents, but
      there is insufficient information on their effects on young adult rodents. The
      aim of this study was to compare the effects of single and repeated exposure to
      desflurane and sevoflurane on spatial learning and memory functions in young
      adult mice. Balb/c mice (2 months old) were randomly divided into six equal
      groups (n = 8). The groups with single inhalation were exposed to 3.3%
      sevoflurane or 7.8% desflurane or vehicle gas for 4 h, respectively. The groups
      with repeated inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or
      vehicle gas for 2 h a day during 5 consecutive days. Spatial learning and memory
      were tested in the Morris water maze 24 h after exposure. In the learning phase,
      the parameters associated with finding the hidden platform and swimming speed,
      and in the memory phase, time spent in the target quadrant and the adjacent
      quadrants, were assessed and compared between the groups. In the 4-day learning
      process, there was no significant difference between the groups in terms of mean
      latency to platform, mean distance traveled and average speed (P > 0.05). During
      the memory-test phase, all mice exhibited spatial memory, but there was no
      significant difference between the groups in terms of time spent in the target
      quadrant (P > 0.05). Sevoflurane and desflurane anesthesia did not impair
      acquisition learning and retention memory in young adult mice.

PMID- 23551532
TI  - Validation of a new panel of automated chemiluminescence assays for von
      Willebrand factor antigen and activity in the screening for von Willebrand
      disease.
AB  - INTRODUCTION: The diagnosis of von Willebrand disease (VWD) largely depends on
      the results of von Willebrand factor (VWF) antigen and activity. Recently, a new
      automated VWF:RCo assay on Acustar was developed. This assay panel for VWD also
      contains a new antigen (VWF:Ag) test. In this study, both chemiluminescence tests
      (HemosIL VWF:Ag and VWF:RCo) were evaluated. MATERIALS AND METHODS: Imprecision,
      limit of detection (LOD), and linearity were evaluated. Method comparison (with
      VWF:Ag latex assay and VWF:RCo by aggregometry) was performed and diagnostic
      performance of the new test panel was examined. RESULTS: The imprecision was 7%,
      and the LOD was 0.2 IU/dL for both assays. Dilution series showed a large
      linearity for both HemosIL VWF:Ag (0-300 IU/dL) and VWF:RCo (0-200 IU/dL) and
      method comparison studies revealed good agreement with the currently used VWD
      panel. The new panel showed adequate diagnostic performance: diagnostic
      sensitivity was 100% and diagnostic specificity 82% compared with the VWF:Ag
      latex assay and VWF:RCo by aggregometry. In addition, the new HemosIL Acustar
      VWF:Ag and HemosIL Acustar VWF:RCo are more sensitive for VWD than the currently
      used assays. CONCLUSIONS: This new VWD test panel has adequate laboratory
      characteristics and allows fully automated and simultaneous analysis of the
      VWF:Ag and VWF:RCo.

PMID- 23551533
TI  - Epidural hematoma following implantation of a permanent spinal cord stimulator
      paddle.

PMID- 23551535
TI  - Hypoxia, energy balance and obesity: from pathophysiological mechanisms to new
      treatment strategies.
AB  - High altitude exposure is often accompanied by weight loss. Postulated mechanisms
      are a reduction of nutritional energy intake, a reduction of intestinal energy
      uptake from impaired intestinal function and increased energy expenditure. Beyond
      the field of altitude, there are good reasons for renewed interest in the
      relationship between hypoxia and energy balance. The increasing prevalence of
      obesity and associated comorbidities represent a major health concern. Obesity is
      frequently associated with sleep disorders leading to intermittent systemic
      hypoxia with deleterious cardiovascular and metabolic consequences. Hypoxic
      regions may be present within hypertrophic white adipose tissue leading to
      chronic systemic inflammation. Among the increasing number of people commuting to
      altitude for work or leisure, obesity is a risk factor for acute mountain
      sickness. Paradoxically, exposure to intermittent hypoxia might be considered as
      a means to lose body mass and to improve metabolic risk factors. Daytime exposure
      to intermittent hypoxia has been used to treat hypertension in former Soviet
      Union countries and is now being experimented elsewhere. Such intermittent
      hypoxic exposure at rest or during exercise may lead to improvement in body
      composition and health status with improved exercise tolerance, metabolism and
      systemic arterial pressure. Future research should confirm whether hypoxic
      training could be a new treatment strategy for weight loss and comorbidities in
      obese subjects and elucidate the underlying mechanisms and signalling pathways.

PMID- 23551534
TI  - Bone marrow osteoblast vulnerability to chemotherapy.
AB  - Osteoblasts are a major component of the bone marrow microenvironment, which
      provide support for hematopoietic cell development. Functional disruption of any
      element of the bone marrow niche, including osteoblasts, can potentially impair
      hematopoiesis. We have studied the effect of two widely used drugs with different
      mechanisms of action, etoposide (VP16) and melphalan, on murine osteoblasts at
      distinct stages of maturation. VP16 and melphalan delayed maturation of
      preosteoblasts and altered CXCL12 protein levels, a key regulator of
      hematopoietic cell homing to the bone marrow. Sublethal concentrations of VP16
      and melphalan also decreased the levels of several transcripts which contribute
      to the composition of the extracellular matrix (ECM) including osteopontin (OPN),
      osteocalcin (OCN), and collagen 1A1 (Col1a1). The impact of chemotherapy on
      message and protein levels for some targets was not always aligned, suggesting
      differential responses at the transcription and translation or protein stability
      levels. As one of the main functions of a mature osteoblast is to synthesize ECM
      of a defined composition, disruption of the ratio of its components may be one
      mechanism by which chemotherapy affects the ability of osteoblasts to support
      hematopoietic recovery coincident with altered marrow architecture. Collectively,
      these observations suggest that the osteoblast compartment of the marrow
      hematopoietic niche is vulnerable to functional dysregulation by damage imposed
      by agents frequently used in clinical settings. Understanding the mechanistic
      underpinning of chemotherapy-induced changes on the hematopoietic support
      capacity of the marrow microenvironment may contribute to improved strategies to
      optimize patient recovery post-transplantation.

PMID- 23551537
TI  - You betcha ....

PMID- 23551536
TI  - An immunohistochemical evaluation of the proteins Wnt1 and glycogen synthase
      kinase (GSK)-3beta in invasive breast carcinomas.
AB  - AIMS: Our purpose was to investigate, in breast carcinomas, the prognostic
      importance of the proteins Wnt1 and glycogen synthasekinase (GSK)-3beta, and
      their associations with classic clinicopathological indices. METHODS AND RESULTS:
      Immunohistochemistry was performed on paraffin-embedded tissue specimens from 288
      invasive breast carcinomas to detect the expression of the proteins Wnt1,
      GSK3beta, oestrogen receptor (ER), progesterone receptor (PR), erbB2, p53, Ki67,
      caspase-3 and beta-catenin. Both Wnt1 and GSK3beta were detected predominantly in
      the cytoplasm of the invasive tumour cells and the in-situ component, while
      GSK3beta was also detected in the stromal fibroblasts. Wnt1 immunoreactivity in
      the invasive tumour cells showed an inverse association with histological grade
      (P = 0.002), Ki67 (P = 0.008) and p53 (P = 0.031), while its relation with ER,
      erbB2 and caspase-3 was found to be positive (P = 0.007, P = 0.018 and P = 0.03,
      respectively). Cytoplasmic Wnt1 expression was related to a favourable prognosis
      within the subgroup of patients with stage II disease (P = 0.032). CONCLUSIONS:
      Wnt1 expression in the invasive tumour cells seems to promote differentiation and
      apoptosis, while being related inversely to proliferation. Therefore, this
      suggests its participation in the primary stages of breast carcinogenesis. The
      latter is supported further by the immunodetection of Wnt1 in in-situ carcinomas.

PMID- 23551538
TI  - Managing the difficult penile prosthesis patient.
AB  - INTRODUCTION: Inflatable penile prostheses (IPPs) are associated with excellent
      long-term outcomes and patient/partner satisfaction. A small percentage of
      patients remain dissatisfied, despite acceptable surgical results. AIMS: This
      study aims to evaluate factors associated with patient satisfaction and
      dissatisfaction, define patient characteristics, which may identify elevated risk
      of postoperative dissatisfaction, and describe management strategies to optimize
      functional and psychological patient outcomes. METHODS: A review of urologic and
      non-urologic cosmetic surgery literature was performed to identify factors
      associated with patient satisfaction/dissatisfaction. Emphasis was placed on
      articles defining "high risk" or psychologically challenging patients. MAIN
      OUTCOME MEASURES: Preoperative factors associated with patient
      satisfaction/dissatisfaction and character traits, which may identify elevated
      risk of postoperative dissatisfaction or otherwise indicate a psychologically
      challenging patient. RESULTS: Contemporary patient and partner satisfaction rates
      following IPP are 92-100% and 91-95%, respectively. Factors associated with
      satisfaction include decreased preoperative expectations, favorable female
      partner sexual function, body mass index <=30, and absence of Peyronie's disease
      or prior prostatectomy. Determinants of dissatisfaction include perceived/actual
      loss of penile length, decreased glanular engorgement, altered
      erectile/ejaculatory sensation, pain, diminished cosmetic outcome, difficulty
      with device function, partner dissatisfaction and perception of unnatural
      sensation, complications, and extent of alternative treatments offered.
      Personality characteristics which may indicate psychologically challenging IPP
      patients include obsessive/compulsive tendencies, unrealistic expectations,
      patients undergoing revision surgery, those seeking multiple surgical opinions,
      feeling of entitlement, patients in denial of their prior erectile/sexual
      function and current disease status, or those with other psychiatric disorders.
      The mnemonic CURSED Patient is presented: "Compulsive/obsessive, Unrealistic,
      Revision, Surgeon Shopping, Entitled, Denial, and Psychiatric." CONCLUSIONS:
      Although the majority of IPP patients experience excellent, durable satisfaction
      and outcomes, a challenging subset of patients may be at increased risk of
      postoperative dissatisfaction. Appropriate recognition/prevention and management
      of this cohort may help to establish and strengthen relationships, reduce
      physical, emotional, and legal risk, and ultimately enhance patient satisfaction.

PMID- 23551539
TI  - Pudendal neuromodulation for sexual dysfunction.

PMID- 23551541
TI  - New developments in education and training in sexual medicine.
AB  - INTRODUCTION.: The past 12 months have been historic ones for the field of Sexual
      Medicine in that we have seen the creation of the European Board examination in
      Sexual Medicine with the title of "Fellow of the European Committee on Sexual
      Medicine" (FECSM) offered to successful candidates. AIM.: The study aims to
      promote a high standard of care in Sexual Medicine. METHODS.: An important way of
      promoting high standards of care is by the development of training, regulation,
      and assessment framework. The background to these developments and the recent
      educational activities of the European Society for Sexual Medicine (ESSM) are
      described in this article. RESULTS.: The creation of the Multidisciplinary Joint
      Committee on Sexual Medicine (MJCSM) under the auspices of the European Union of
      Medical Specialists, with the primary purpose to develop the highest possible
      standards of training in Sexual Medicine in Europe, made it possible to create a
      process for qualification in Sexual Medicine. The ESSM educational activities
      created opportunities to support trainees in Sexual Medicine and the first MJCSM
      exam was held in Amsterdam with a high overall success rate. CONCLUSION.: These
      activities are intended to improve quality. The FECSM examination is the first of
      its type and provides a real opportunity for Sexual Medicine physicians to
      demonstrate and document their knowledge.

PMID- 23551542
TI  - Summit on medical school education in sexual health: report of an expert
      consultation.
AB  - INTRODUCTION.: Medical education in sexual health in the United States and Canada
      is lacking. Medical students and practicing physicians report being underprepared
      to adequately address their patients' sexual health needs. Recent studies have
      shown little instruction on sexual health in medical schools and little consensus
      around the type of material medical students should learn. To address and manage
      sexual health issues, medical students need improved education and training.
      AIM.: This meeting report aims to present findings from a summit on the current
      state of medical school education in sexual health and provides recommended
      strategies to better train physicians to address sexual health. METHODS.: To
      catalyze improvements in sexual health education in medical schools, the summit
      brought together key U.S. and Canadian medical school educators, sexual health
      educators, and other experts. Attendees reviewed and discussed relevant data and
      potential recommendations in plenary sessions and then developed key
      recommendations in smaller breakout groups. RESULTS.: Findings presented at the
      summit demonstrate that the United States and Canada have high rates of poor
      sexual health outcomes and that sexual health education in medical schools is
      variable and in some settings diminished. To address these issues, government,
      professional, and student organizations are working on efforts to promote sexual
      health. Several universities already have sexual health curricula in place.
      Evaluation mechanisms will be essential for developing and refining sexual health
      education. CONCLUSIONS.: To be effective, sexual health curricula need to be
      integrated longitudinally throughout medical training. Identifying faculty
      champions and supporting student efforts are strategies to increase sexual health
      education. Sexual health requires a multidisciplinary approach, and cross-sector
      interaction between various public and private entities can help facilitate
      change. Areas important to address include: core content and placement in the
      curriculum; interprofessional education and training for integrated care;
      evaluation mechanisms; faculty development and cooperative strategies. Initial
      recommendations were drafted for each.

PMID- 23551543
TI  - Patient highlights. Delayed ejaculation.

PMID- 23551544
TI  - Depressive mood and frontal alpha asymmetry during the luteal phase in
      premenstrual dysphoric disorder.
AB  - AIMS: Patients with premenstrual dysphoric disorder (PMDD) experience moderate to
      severe physical and mood symptoms during the luteal phase of their menstrual
      cycle. The purposes of this study were to examine whether there were significant
      differences in frontal alpha asymmetry between PMDD and non-PMDD women during a
      depressive induction condition during the luteal and follicular phases and to
      examine the relations between premenstrual distress and depressive symptoms, and
      frontal alpha asymmetry. MATERIAL AND METHODS: The participants included 12
      college women with PMDD and 12 without PMDD as controls. Frontal
      electroencephalograms (F3/F4) were measured during the luteal and follicular
      phases of the menstrual cycle in the following sequence: resting baseline,
      depressive induction, depressive recall, recovery, and relaxation. Premenstrual
      distress questionnaires and the Beck Depression Inventory II were administered.
      RESULTS: The participants with PMDD had higher frontal alpha asymmetry than those
      without PMDD during the depressive induction and relaxation conditions only
      during the luteal phase. For PMDD and non-PMDD during the luteal phase, a
      positive correlation was observed between negative affect (measured by
      premenstrual distress questionnaires) and frontal alpha asymmetry under the
      depressive induction stage. In addition, higher Beck Depression Inventory II
      somatic depression was positively correlated with frontal alpha asymmetry under
      the depressive induction stage. CONCLUSIONS: This study supports the significant
      difference between PMDD and non-PMDD on frontal alpha asymmetry, and frontal
      alpha asymmetry was related to negative affect and somatic depression, while
      participants with PMDD were in the depressive mood during the luteal phase.

PMID- 23551545
TI  - Perniosis in an infant treated with topical nitroglycerine.
AB  - Treatment of perniosis with topical nitroglycerin ointment is reported in a 6
      month-old boy. 

PMID- 23551547
TI  - Results of single-center screening for chronic hepatitis E in children after
      liver transplantation and report on successful treatment with ribavirin.
AB  - RNA screening for HEV in 22 liver-transplanted children with chronic graft
      hepatitis out of a cohort of 267 liver-transplanted children detected a single
      patient with chronic HEV infection. Although this patient remained viremic for 33
      months, anti-HEV-IgG was not detectable with MP assay but with Wantai assay. We
      present the first case of successful ribavirin therapy in an immunosuppressed
      child with chronic HEV infection. In conclusion, chronic HEV infection in
      immunosuppressed children may not be detectable employing serological assays.
      Therefore, the most reliably screening method is screening for HEV-RNA. Chronic
      HEV infection in children can successfully be treated with ribavirin.

PMID- 23551548
TI  - Pseudopapillary pattern in intra-operative squash smear preparations of central
      nervous system germinomas.
AB  - BACKGROUND: Although the morphology of central nervous system (CNS) germ cell
      tumours is very similar to that of gonadal germ cell tumours, some architectural
      changes may dominate the microscopic appearance of CNS germinomas leading to
      misdiagnosis at low-power magnification. METHODS: We report five cases of CNS
      germinoma demonstrating delicate pseudopapillary fronds on squash smear
      preparations. RESULTS: The age of the patients ranged from 5 to 21 years (mean
      14). Three were female and two male. Three patients presented with symptoms of
      diabetes insipidus, including polydipsia and polyuria, while absence seizures,
      meaningless speech, hemiparesia, weight loss, insufficient breast development,
      amenorrhoea and symptoms of raised intracranial pressure were also encountered
      depending on the location of the tumours. Tumours were located in the hypophysis
      in two cases and in the suprasellar region in three. During the intra-operative
      pathological consultation, evenly distributed pseudopapillary or papillary
      structures formed the dominant pattern in the squash preparations of all cases.
      The neoplastic cells were characterized by pale variably vacuolated cytoplasm,
      pleomorphic nuclei with irregular membranes, and several prominent nucleoli.
      Variable numbers of small lymphocytes were also found. CONCLUSION: Intracranial
      germinomas may commonly exhibit a pseudopapillary pattern on squash smears that
      may cause misdiagnosis as neoplasms with papillary morphology. Careful
      examination of cellular details is essential in order to reach the correct
      diagnosis.

PMID- 23551549
TI  - Effects of extracellular DNA and DNA-binding protein on the development of a
      Streptococcus intermedius biofilm.
AB  - AIMS: The aim of this study was to clarify the effects of homologous and
      heterologous extracellular DNAs (eDNAs) and histone-like DNA-binding protein
      (HLP) on Streptococcus intermedius biofilm development and rigidity. METHODS AND
      RESULTS: Formed biofilm mass was measured with 0.1% crystal violet staining
      method and observed with a scanning electron microscope. The localizations of
      eDNA and extracellular HLP (eHLP) in formed biofilm were detected by staining
      with 7-hydoxyl-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) and anti-HLP antibody
      without fixation, respectively. DNase I treatment (200 U ml(-1)) markedly
      decreased biofilm formation and cell density in biofilms. Colocalization of eHLP
      and eDNA in biofilm was confirmed. The addition of eDNA (up to 1 MUg ml(-1))
      purified from Strep. intermedius, other Gram-positive bacteria, Gram-negative
      bacteria, or human KB cells into the Strep. intermedius culture increased the
      biofilm mass of all tested strains of Strep. intermedius, wild-type, HLP
      downregulated strain and control strains. In contrast, the addition of eDNA (>1
      MUg ml(-1)) decreased the biofilm mass of all Strep. intermedius strains.
      CONCLUSIONS: These findings demonstrated that eDNA and eHLP play crucial roles in
      biofilm development and its rigidity. SIGNIFICANCE AND IMPACT OF THE STUDY: eDNA-
      and HLP-targeting strategies may be applicable to novel treatments for bacterial
      biofilm-related infectious diseases.

PMID- 23551550
TI  - The influence of background diabetic retinopathy in the second eye on rates of
      progression of diabetic retinopathy between 2005 and 2010.
AB  - PURPOSE: The Gloucestershire Diabetic Eye Screening Programme offers annual
      digital photographic screening for diabetic retinopathy to a countywide
      population of people with diabetes. This study was designed to investigate
      progression of diabetic retinopathy in this programme of the English NHS Diabetic
      Eye Screening Programme. METHODS: Mydriatic digital retinal photographs of people
      with diabetes screened on at least 2 occasions between 2005 and 2010 were graded
      and included in this study if the classification at first screening was no DR
      (R0), background DR in one (R1a) or both eyes (R1b). Times to detection of
      referable diabetic retinopathy (RDR) comprising maculopathy (M1),
      preproliferative (R2) or proliferative retinopathy (R3) were analysed using
      survival models. RESULTS: Data were available on 19 044 patients, 56% men, age at
      screening 66 (57-74) years (median, 25th, 75th centile). A total of 8.3% of those
      with R1a and 28.2% of those with R1b progressed to any RDR, hazard ratios 2.9
      [2.5-3.3] and 11.3 [10.0-12.8]. Similarly 7.1% and 0.11% of those with R1a
      progressed to M1 and R3, hazard ratios 2.7 [2.3-3.2] and 1.6 [0.5-5.0], compared
      to 21.8% and 1.07% of those with R1b, hazard ratio 9.1 [7.8-10.4] and 15.0 [7.1
      31.5]. CONCLUSIONS: The risk of progression is significantly higher for those
      with background DR in both eyes than those with background retinopathy in only
      one or in neither eye.

PMID- 23551552
TI  - Commentary on "comparison of a fractional microplasma radiofrequency technology
      and carbon dioxide fractional laser for the treatment of atrophic acne scars: a
      randomized split-face clinical study".

PMID- 23551551
TI  - Phosphorylation-dependent localization of the response regulator FrzZ signals
      cell reversals in Myxococcus xanthus.
AB  - The life cycle of Myxococcus xanthus includes co-ordinated group movement and
      fruiting body formation, and requires directed motility and controlled cell
      reversals. Reversals are achieved by inverting cell polarity and re-organizing
      many motility proteins. The Frz chemosensory pathway regulates the frequency of
      cell reversals. While it has been established that phosphotransfer from the
      kinase FrzE to the response regulator FrzZ is required, it is unknown how
      phosphorylated FrzZ, the putative output of the pathway, targets the cell
      polarity axis. In this study, we used Phos-tag SDS-PAGE to determine the cellular
      level of phospho-FrzZ under different growth conditions and in Frz signalling
      mutants. We detected consistent FrzZ phosphorylation, albeit with a short half
      life, in cells grown on plates, but not from liquid culture. The available pool
      of phospho-FrzZ correlated with reversal frequencies, with higher levels found in
      hyper-reversing mutants. Phosphorylation was not detected in hypo-reversing
      mutants. Fluorescence microscopy revealed that FrzZ is recruited to the leading
      cell pole upon phosphorylation and switches to the opposite pole during
      reversals. These results are consistent with the hypothesis that the Frz pathway
      modulates reversal frequency through a localized response regulator that targets
      cell polarity regulators at the leading cell pole.

PMID- 23551553
TI  - Commentary: how much is too much? Tourniquets and digital ischemia.

PMID- 23551554
TI  - Commentary: the growing skin cancer problem.

PMID- 23551555
TI  - Commentary: transecting melanomas: does it matter?

PMID- 23551556
TI  - Commentary: prognosis of patients with transected melanomas.

PMID- 23551557
TI  - Commentary: bilobed flap for reconstruction of small alar rim defects.

PMID- 23551558
TI  - "Waste knot, want knot": pearls for optimizing the use of suture packaging
      material in dermatologic surgery.

PMID- 23551559
TI  - Monopolar radiofrequency treatment in Asian skin: do multiple RF treatments over
      time have beneficial effects? An observational report with long-term follow-up in
      eight patients.

PMID- 23551560
TI  - Insulin-like growth factor-1 predicts cognitive functions at 2-year follow-up in
      early, drug-naive Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Cognitive impairment is common in Parkinson's disease
      (PD), even in the early stages. We aimed to assess the relationship between
      insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naive
      patients with PD. METHODS: Serum IGF-1 was measured in 65 early, drug-naive
      patients with PD that underwent a complete neuropsychological battery at baseline
      and after 2 years. Linear regression analysis was used to evaluate the
      relationships between neuropsychological scores and IGF-1. Repeated-measures
      anova was applied to assess changes in neuropsychological variables over time.
      RESULTS: At baseline, IGF-1 levels were related to phonological fluency. At
      follow-up, IGF-1 levels were associated with the Rey auditory verbal learning
      test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal
      span and Benton judgement of the line orientation test. Patients with low IGF-1
      levels at baseline showed a significantly faster decline of performances than
      patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and
      interference task of the Stroop test. CONCLUSIONS: Low serum IGF-1 levels are
      related to poor performance on executive tasks in early, drug-naive patients with
      PD, and may predict poor performance on attention/executive and verbal memory
      tasks after a 2-year follow-up.

PMID- 23551561
TI  - Knowledge about medications and products to prevent and treat pressure ulcers: a
      cross-sectional survey of nurses and physicians in a primary health care setting.
AB  - AIMS AND OBJECTIVES: To report on a study of what primary care nurses and
      physicians know about medications and healthcare products to prevent and treat
      pressure ulcers. BACKGROUND: The prevention and treatment of pressure ulcers has
      generally become the responsibility of the nursing staff; this has resulted in
      studies of nurses' knowledge of this task, although few studies include
      physicians in their analysis. DESIGN: Cross-sectional survey conducted in North
      Girona (Province) Primary Care Services from February to April 2010. METHODS: The
      study questionnaire had three sections: sociodemographic data, questions about
      division of responsibility for the care of patients with pressure ulcers or at
      risk of developing them, and 36 statements based on the recommendations in
      clinical practice guidelines provided by well-recognised national and
      international institutions. RESULTS: Eighty-one nurses (64.8%) and 46 physicians
      (36.8%) responded to this study. Nurses had greater responsibility for the care
      of pressure ulcers, made greater use of medical prescriptions to obtain supplies
      if not available in the primary care centre, were more familiar with the site's
      clinical practice guidelines on the topic and showed better adherence to their
      recommendations. Nurses also had better knowledge than the participating
      physicians of the use of medications and healthcare products to heal or to
      prevent pressure ulcers. CONCLUSIONS: Nurses had sufficient knowledge and more
      appropriate skills than the participating physicians for the prescription of
      medications and healthcare products for the prevention and treatment of pressure
      ulcers. RELEVANCE TO CLINICAL PRACTICE: The data demonstrated that nurses have
      sufficient knowledge and skill to provide wound care and could safely write these
      prescriptions, although Spanish law permitting nurse prescription is not fully
      implemented.

PMID- 23551562
TI  - The evolution and diversification of plant microtubule-associated proteins.
AB  - Plant evolution is marked by major advances in structural characteristics that
      facilitated the highly successful colonization of dry land. Underlying these
      advances is the evolution of genes encoding specialized proteins that form novel
      microtubular arrays of the cytoskeleton. This review investigates the evolution
      of plant families of microtubule-associated proteins (MAPs) through the recently
      sequenced genomes of Arabidopsis thaliana, Oryza sativa, Selaginella
      moellendorffii, Physcomitrella patens, Volvox carteri and Chlamydomonas
      reinhardtii. The families of MAPs examined are AIR9, CLASP, CRIPT, MAP18, MOR1,
      TON, EB1, AtMAP70, SPR2, SPR1, WVD2 and MAP65 families (abbreviations are defined
      in the footnote to Table 1). Conjectures are made regarding the evolution of MAPs
      in plants in relation to the evolution of multicellularity, oriented cell
      division and vasculature. Angiosperms in particular have high numbers of proteins
      that are involved in promotion of helical growth or its suppression, and novel
      plant microtubular structures may have acted as a catalyst for the development of
      novel plant MAPs. Comparisons of plant MAP gene families with those of animals
      show that animals may have more flexibility in the structure of their microtubule
      cytoskeletons than plants, but with both plants and animals possessing many MAP
      splice variants.

PMID- 23551563
TI  - The effect of hydrofluoric acid treatment of titanium and titanium dioxide
      surface on primary human osteoblasts.
AB  - OBJECTIVE: The aim of the study was to investigate solely the effect of fluoride
      on the surface chemistry of polycrystalline ceramic titanium dioxide (TiO2 ) and
      metallic titanium (Ti) and its effect on proliferation and differentiation of
      primary human osteoblasts (NHO). MATERIALS AND METHODS: The NHO cells were
      exposed to fluoride-modified and unmodified samples for 1, 3, 7, 14 and 21 days.
      The fluoride effect on the mRNA expression was quantified and measured. The
      secretion of cytokines and interleukins in the cell culture medium was measured
      by Luminex, gene expression by RT-PCR, and compared with untreated controls. The
      effect on cell growth after 1 and 3 days in culture was measured using [(3) H]
      thymidine incorporation. Fluoride release was measured using an ion-selective
      electrode. The surfaces were examined by X-ray photoelectron spectroscopy and
      profilometry. RESULTS: The fluoride release study detected that fluoride content
      easily washed off in TiO2 coins when compared with Ti coins. No increase in cell
      proliferation was found among fluoride-modified TiO2 surfaces compared with
      controls, except for washed Ti coins with fluoride modification. The cell
      differentiation with regard to gene expression showed no significant differences
      in both fluoride-modified and unmodified samples and less effect on protein
      release for all groups. CONCLUSIONS: The fluoride from hydrofluoric acid
      treatment on Ti and TiO2 surfaces gave no specific effect on primary human
      osteoblast cells. The study indicates that the released fluoride is not the
      unique factor for the bioactivity of Ti and TiO2 surfaces.

PMID- 23551564
TI  - Effects of immediate and delayed loading on peri-implant trabecular structures: a
      cone beam CT evaluation.
AB  - PURPOSE: To develop a method for characterizing trabecular bone microarchitecture
      using cone beam computed tomography (CBCT) and to evaluate trabecular bone
      changes after rehabilitation using immediate versus delayed implant protocols.
      MATERIALS AND METHODS: Six mongrel dogs randomly received 27 titanium implants in
      the maxillary incisor or mandibular premolar areas, following one of four
      protocols: (1) normal extraction socket healing; (2) immediate implant placement
      and immediate loading; (3) delayed implant placement and delayed loading; (4)
      delayed implant placement and immediate loading. The animals were euthanized at 8
      weeks, and block biopsies were scanned using high resolution CBCT. Standard bone
      structural variables were assessed in coronal, middle, and apical levels.
      RESULTS: Coronal and middle regions had more compact, more platelike, and thicker
      trabeculae. Protocols (2), (3), and (4) had significantly higher values (p <
      0.001) than protocol (1) for bone surface density, bone surface volume ratio, and
      connectivity density, while significantly lower values (p < 0.001) were found for
      trabecular separation and fractal dimension. However, protocols (2), (3), and (4)
      did not show significantly different bone remodeling. CONCLUSIONS: Compared with
      normal extraction healing, the implant protocols have an improved bone structural
      integration. Results do not suggest a different bone remodeling pattern when a
      delayed versus an immediate implant protocol is used.

PMID- 23551566
TI  - Communicating with brain tumor patients about driving: are we falling short of
      the mark?

PMID- 23551565
TI  - 'It's more about the heroin': injection drug users' response to an overdose
      warning campaign in a Canadian setting.
AB  - AIMS: To assess heroin injectors' perceptions of and responses to a warning
      issued by public health officials regarding high-potency heroin and increases in
      fatal overdoses. DESIGN: Semi-structured qualitative interviews. SETTING:
      Vancouver, Canada. PARTICIPANTS: Eighteen active heroin injectors. MEASUREMENTS:
      Semi-structured interview guide focussing on heroin injectors' perceptions of and
      responses to the overdose warning, including reasons for failing to adhere to
      risk reduction recommendations. FINDINGS: Although nearly all participants were
      aware of the warning, their recollections of the message and the timing of its
      release were obscured by on-going social interactions within the drug scene
      focussed on heroin quality. Many injection drug users reported seeking the high
      potency heroin and nearly all reported no change in overdose risk behaviours.
      Responses to the warning were shaped by various social, economic and structural
      forces that interacted with individual behaviour and undermined efforts to
      promote behavioural change, including sales tactics employed by dealers, poverty,
      the high cost and shifting quality of available heroin, and risks associated with
      income-generating activities. Individual-level factors, including emotional
      suffering, withdrawal, entrenched injecting routines, perceived invincibility and
      the desire for intense intoxication also undermined risk reduction messages.
      CONCLUSIONS: Among heroin injectors in British Columbia, a 2011 overdose warning
      campaign appeared to be of limited effectiveness and also produced unintended
      negative consequences that exacerbated overdose risk.

PMID- 23551567
TI  - Interference of cerebrospinal fluid white blood cell counts performed on the
      Sysmex XT-4000i by yeast and bacteria.

PMID- 23551568
TI  - Favourable long-term outcomes with brachytherapy-based regimens in men <=60 years
      with clinically localized prostate cancer.
AB  - OBJECTIVE: To report long-term outcomes of men <=60 years treated with
      brachytherapy (BT) for low- and intermediate-risk prostate cancer. PATIENTS AND
      METHODS: Of 1655 patients treated with BT for clinically localized prostate
      cancer between January 1998 and May 2008 at Memorial Sloan-Kettering Cancer
      Center, 236 patients with National Comprehensive Cancer Network low- (n = 178) or
      intermediate-risk (n = 58) prostate cancer were <=60 years old with a 3-year
      minimum follow-up, and represent the subjects of this report. Brachytherapy was
      given either as monotherapy (n = 169) or with external beam radiation therapy
      (EBRT; n = 67). Forty-four patients (19%) received neoadjuvant cytoreductive
      hormone therapy. The 'nadir+2' definition was used for prostate-specific antigen
      (PSA) recurrence. Common Terminology Criteria for Acute Events (CTCAE) v 3.0 was
      used to grade genitourinary (GU) and gastrointestinal (GI) toxicity. Potency was
      defined as the ability to obtain an erection suitable for intercourse or an
      International Index of Erectile Function score >= 22. The Kaplan-Meier method and
      Cox regression were used for statistical analysis. The median follow-up was 83
      months. RESULTS: The 8-year PSA relapse-free survival (RFS), cancer-specific and
      overall survival rates for the entire cohort were 96, 99 and 96%, respectively.
      For patients with low-risk disease, the 8-year PSA RFS rate was 97% and for
      intermediate-risk patients it was 94% (P = 0.34). There was no difference in PSA
      RFS between BT alone and combined therapy (P = 0.17). Late grade >= 2 GU and GI
      toxicity was 14 and 3%, respectively. Of 150 patients potent before treatment, 76
      (51%) were potent at last follow-up, with 50/76 (66%) using no medication. There
      was no significant difference in post-treatment potency between BT alone and BT
      with EBRT (P = 0.74). CONCLUSIONS: Brachytherapy provides patients aged <= 60
      years with low- and intermediate-risk prostate cancer with excellent outcomes and
      has a low risk of significant long-term GU or GI morbidity. Erectile function is
      preserved in >50% of patients and the majority do not require erectile
      dysfunction medication.

PMID- 23551569
TI  - A prospective comparison of totally minimally invasive versus open Ivor Lewis
      esophagectomy.
AB  - The majority of esophagectomies in Western parts of the world are performed by a
      transthoracic approach reflecting the prevalence of adenocarcinoma of the lower
      esophagus or esophagogastric junction. Minimally invasive esophagectomy (MIE) has
      been reported in a variety of formats, but there are no series that directly
      compare totally minimally invasive thoracolaparoscopic 2 stage esophagectomy (MIE
      2) with open Ivor Lewis (IVL). A prospective single-center cohort study of
      patients undergoing elective MIE-2 or IVL between January 2005 and November 2010
      was performed. Short-term clinicopathologic outcomes were recorded using
      validated systems. One hundred and six patients (median age 66, range 36-85, 88 M
      : 18 F) underwent two-stage esophagectomy (53 MIE-2 and 53 IVL). Patient
      demographics (age, sex, body mass index, American Society of Anesthesiologists
      grade, tumor characteristics, neoadjuvant chemotherapy, and TNM stage) were
      comparable between the two groups. Outcomes for MIE-2 and IVL were comparable for
      anastomotic leak rates (5 [9%] vs. 2 [4%], P= 0.241), resection margin clearance
      (R0) (43 [81%] vs. 38 [72%], P= 0.253), median lymph node yield (19 vs. 18, P=
      0.584), and median length of stay (12 [range 7-91] vs. 12 [range 7-101] days),
      respectively. Blood loss was significantly less for MIE-2 compared with IVL
      (median 300 [range 0-1250] mL vs. 400 [range 0-3000] mL, respectively, P= 0.021).
      MIE-2 in this series of selected patients supports its efficacy, when performed
      by an experienced minimally invasive surgical team. A well-designed multicenter
      trial addressing clinical effectiveness is now required.

PMID- 23551570
TI  - A small-scale land-sparing approach to conserving biological diversity in
      tropical agricultural landscapes.
AB  - Two contrasting strategies have been proposed for conserving biological diversity
      while meeting the increasing demand for agricultural products: land sparing and
      land sharing production systems. Land sparing involves increasing yield to reduce
      the amount of land needed for agriculture, whereas land-sharing agricultural
      practices incorporate elements of native ecosystems into the production system
      itself. Although the conservation value of these systems has been extensively
      debated, empirical studies are lacking. We compared bird communities in shade
      coffee, a widely practiced land-sharing system in which shade trees are
      maintained within the coffee plantation, with bird communities in a novel, small
      scale, land-sparing coffee-production system (integrated open canopy or IOC
      coffee) in which farmers obtain higher yields under little or no shade while
      conserving an area of forest equal to the area under cultivation. Species
      richness and diversity of forest-dependent birds were higher in the IOC coffee
      farms than in the shade coffee farms, and community composition was more similar
      between IOC coffee and primary forest than between shade coffee and primary
      forest. Our study represents the first empirical comparison of well-defined land
      sparing and land sharing production systems. Because IOC coffee farms can be
      established by allowing forest to regenerate on degraded land, widespread
      adoption of this system could lead to substantial increases in forest cover and
      carbon sequestration without compromising agricultural yield or threatening the
      livelihoods of traditional small farmers. However, we studied small farms (<5
      ha); thus, our results may not generalize to large-scale land-sharing systems.
      Furthermore, rather than concluding that land sparing is generally superior to
      land sharing, we suggest that the optimal approach depends on the crop, local
      climate, and existing land-use patterns.

PMID- 23551571
TI  - The development and validation of the Male Genital Self-Image Scale: results from
      a nationally representative probability sample of men in the United States.
AB  - INTRODUCTION: Numerous factors may affect men's sexual experiences, including
      their health status, past trauma or abuse, medication use, relationships, mood,
      anxiety, and body image. Little research has assessed the influence of men's
      genital self-image on their sexual function or behaviors and none has done so in
      a nationally representative sample. AIMS: The purpose of this study was to, in a
      nationally representative probability sample of men ages 18 to 60, assess the
      reliability and validity of the Male Genital Self-Image Scale (MGSIS), and to
      examine the relationship between scores on the MGSIS and men's scores on the
      International Index of Erectile Function (IIEF). METHODS: The MGSIS was developed
      in two stages. Phase One involved a review of the literature and an analysis of
      cross-sectional survey data. Phase Two involved an administration of the scale
      items to a nationally representative sample of men in the United States ages 18
      to 60. MAIN OUTCOME MEASURES: Measures include demographic items, the IIEF, and
      the MGSIS. RESULTS: Overall, most men felt positively about their genitals.
      However, 24.6% of men expressed some discomfort letting a healthcare provider
      examine their genitals and about 20% reported dissatisfaction with their genital
      size. The MGSIS was found to be reliable and valid, with the MGSIS-5 (consisting
      of five items) being the best fit to the data. CONCLUSION: The MGSIS was found to
      be a reliable and valid measure. In addition, men's scores on the MGSIS-5 were
      found to be positively related to men's scores on the IIEF.

PMID- 23551572
TI  - Epithelioid angiomyolipoma of the kidney: radiological imaging.
AB  - OBJECTIVES: To review the imaging findings of renal epithelioid angiomyolipomas.
      METHODS: Eight patients treated at two institutions were pathologically diagnosed
      as having epithelioid angiomyolipoma. All of them underwent computed tomography,
      and four underwent magnetic resonance imaging. The tumor size, existence of fat,
      heterogeneity, computed tomography attenuation, degree of enhancement,
      enhancement pattern and magnetic resonance imaging signal intensity were
      evaluated. RESULTS: Intratumoral fat was not detected in any of the cases. On
      unenhanced computed tomography, the intratumoral attenuation was hyperattenuating
      in six of the seven patients who were examined using this modality. On T2
      weighted images, the signal intensity of the solid component, cyst wall or septum
      was low in three of the four cases. Four of the eight cases were heterogeneous
      solid-type accompanied by hemorrhage, necrosis or hyalinization. One homogeneous
      solid-type lesion was large in size and was pathologically accompanied by neither
      hemorrhage nor necrosis. All three multilocular cystic types were pathologically
      accompanied by massive hemorrhage in the cystic component. One was accompanied by
      spontaneous perirenal hematoma. CONCLUSIONS: The radiological appearance of most
      epithelioid angiomyolipomas has a tendency to be hyperattenuating on unenhanced
      computed tomography images, with low intensities on T2-weighted images. They can
      be heterogeneously solid, homogeneously solid or a multilocular cystic lesion
      with massive hemorrhage.

PMID- 23551573
TI  - Adenomyomectomy, curettage, and then uterine artery pseudoaneurysm occupying the
      entire uterine cavity.
AB  - Uterine artery pseudoaneurysm can occur after cesarean section or traumatic
      delivery, usually manifesting as postpartum hemorrhage. Pregnant women after
      adenomyomectomy sometimes suffer some adverse events, among which uterine rupture
      has been widely acknowledged. We describe a post-abortive woman who had uterine
      artery pseudoaneurysm occupying the entire uterine cavity. She underwent
      adenomyomectomy and became pregnant. She experienced a missed abortion and
      underwent evacuation and curettage, which caused bleeding. Several days later,
      ultrasound revealed an intrauterine mass with marked blood flow. Angiography
      revealed the un-ruptured left uterine artery pseudoaneurysm, with arterial
      embolization stopping the flow within the pseudoaneurysm. Adenomyomectomy with
      subsequent curettage was considered to have caused the pseudoaneurysm. We must be
      cautious that pseudoaneurysm may occur in post-abortive women after
      adenomyomectomy.

PMID- 23551574
TI  - Assessment of temporal and spatial evolution of bacterial communities in a
      biological sand filter mesocosm treating winery wastewater.
AB  - AIMS: To assess the impact of winery wastewater (WW) on biological sand filter
      (BSF) bacterial community structures, and to evaluate whether BSFs can constitute
      alternative and valuable treatment- processes to remediate WW. METHODS AND
      RESULTS: During 112 days, WW was used to contaminate a BSF mesocosm (length 173
      cm/width 106 cm/depth 30 cm). The effect of WW on bacterial communities of four
      BSF microenvironments (surface/deep, inlet/outlet) was investigated using
      terminal-restriction fragment length polymorphism (T-RFLP). BSF achieved high Na
      (95.1%), complete Cl and almost complete chemical oxygen demand (COD) (98.0%) and
      phenolic (99.2%) removals. T-RFLP analysis combined with anosim revealed that WW
      significantly modified the surface and deep BSF bacterial communities.
      CONCLUSIONS: BSF provided high COD, phenolic and salt removals throughout the
      experiment. WW-selected bacterial communities were thus able to tolerate and/or
      degrade WW, suggesting that community composition does not alter BSF
      performances. However, biomass increased significantly in the WW-impacted surface
      sediments, which could later lead to system clogging and should thus be
      monitored. SIGNIFICANCE AND IMPACT OF THE STUDY: BSFs constitute alternatives to
      constructed wetlands to treat agri effluents such as WW. To our knowledge, this
      study is the first unravelling the responses of BSF bacterial communities to
      contamination and suggests that WW-selected BSF communities maintained high
      removal performances.

PMID- 23551575
TI  - Asymmetric dimethylarginine levels in children with sickle cell disease and its
      correlation to tricuspid regurgitant jet velocity.
AB  - BACKGROUND: Pulmonary hypertension (PH) is an increasingly recognized life
      threatening complication in sickle cell disease (SCD), with associated high
      mortality in adults. The prevalence of PH in children with SCD is still unknown.
      The etiology and pathophysiologic mechanisms are still not well understood. AIM
      OF THE STUDY: To assess the plasma levels of asymmetric dimethylarginine (ADMA)
      in children with SCD and its correlation with elevated tricuspid regurgitant jet
      velocity and other hemolytic markers. SUBJECTS & METHODS: This study was carried
      out on a cohort of patients (30) with SCD and 30 healthy children as a control
      group. Certain investigations were carried out for all subjects: CBC, lactate
      dehydrogenase (LDH), ferritin, reticulocytic count, bilirubin, AST, ALT, and
      plasma levels of ADMA. Doppler echocardiography was carried out for all subjects.
      RESULTS: The prevalence of high tricuspid regurgitant velocity (TRV) was 30% in
      SCD patients. ADMA mean plasma level was significantly higher in patients than in
      controls (0.79 +/- 0.15 MUmol/L and 0.46 +/- 0.11 MUmol/L, respectively, P <
      0.001). ADMA was significantly higher in patients with high TRV than those with
      normal TRV (1.10 +/- 0.11 MUmol/L, 0.80 +/- 0.06 MUmol/L, respectively, P <
      0.001). There was a significant positive correlation between ADMA plasma levels
      and TRV >=2.5 m/s (r = 0.475). CONCLUSION: High plasma ADMA levels may be
      implicated in the pathogenesis of increased tricuspid regurgitant jet velocity in
      children with SCD.

PMID- 23551577
TI  - Increased perinatal loss after intrauterine transfusion for alloimmune anaemia
      before 20 weeks of gestation.
AB  - OBJECTIVES: To evaluate and compare perinatal outcome after intrauterine
      transfusions (IUT) performed before and after 20 weeks of gestation. To analyse
      contributing factors. DESIGN: Retrospective analysis. SETTING: The Dutch referral
      centre for fetal therapy. POPULATION: IUTs for fetal alloimmune anaemia. METHODS:
      Fetuses were divided into two groups: fetuses requiring the first IUT before 20
      weeks of gestation (Group 1) and those in which the IUTs started after 20 weeks
      (Group 2). The cause of perinatal loss was classified as procedure-related (PR)
      or not procedure-related (NPR). The cohort was divided into two periods to
      describe the change of perinatal loss over time. MAIN OUTCOME MEASURES: Perinatal
      loss of fetuses requiring the first IUT before 20 weeks of gestation, compared
      with perinatal loss later in gestation. RESULTS: A total of 1422 IUTs were
      performed in 491 fetuses. Perinatal loss rate in Group 1 was higher (7/29 24%
      versus 35/462 8%, P = 0.002). Especially NPR was higher for IUTs performed before
      20 weeks (4/37 11% versus 19/1385 1%, P < 0.001). Kell alloimmunisation was
      overrepresented in Group 1 (7/29 24% versus 52/462 11%, P = 0.04). In a
      multivariate regression analysis, only hydrops was independently associated with
      perinatal loss (P = 0.001). In recent years, a decline in total perinatal loss
      was found (36/224 16% versus 6/267 2%, P < 0.001), but perinatal loss in Group 1
      did not decline (4/224 1.8% versus 3/267 1.1%, P = 0.5). CONCLUSIONS: Perinatal
      loss after IUT performed before 20 weeks of gestation is increased compared with
      loss after IUT performed later in gestation. In addition, we confirmed earlier
      observations that hydrops is a major contributor to adverse outcome. Early and
      timely detection and treatment may prevent hydrops and improve outcome.

PMID- 23551576
TI  - Toll-like receptors in prostate infection and cancer between bench and bedside.
AB  - Toll-Like receptors (TLRs) are a family of evolutionary conserved transmembrane
      proteins that recognize highly conserved molecules in pathogens. TLR-expressing
      cells represent the first line of defence sensing pathogen invasion, triggering
      innate immune responses and subsequently priming antigen-specific adaptive
      immunity. In vitro and in vivo studies on experimental cancer models have shown
      both anti- and pro-tumoural activity of different TLRs in prostate cancer,
      indicating these receptors as potential targets for cancer therapy. In this
      review, we highlight the intriguing duplicity of TLR stimulation by pathogens:
      their protective role in cases of acute infections, and conversely their negative
      role in favouring hyperplasia and/or cancer onset, in cases of chronic
      infections. This review focuses on the role of TLRs in the pathophysiology of
      prostate infection and cancer by exploring the biological bases of the strict
      relation between TLRs and prostate cancer. In particular, we highlight the
      debated question of how reliable mutations or deregulated expression of TLRs are
      as novel diagnostic or prognostic tools for prostate cancer. So far, the
      anticancer activity of numerous TLR ligands has been evaluated in clinical trials
      only in organs other than the prostate. Here we review recent clinical trials
      based on the most promising TLR agonists in oncology, envisaging a potential
      application also in prostate cancer therapy.

PMID- 23551578
TI  - Neuropilin-1 and neuropilin-2 expression in the adenoma-carcinoma sequence of
      colorectal cancer.
AB  - AIMS: Neuropilin-1 (NRP1) and neuropilin-2 (NRP2) are transmembrane glycoproteins
      which interact with vascular endothelial growth factor (VEGF) to prevent tumour
      cell apoptosis and regulate angiogenesis. However, the precise role of NRP1 and
      NRP2 in the adenoma-carcinoma sequence (ACS) of colorectal cancer remains
      unclear, and we aimed to determine this in surgical specimens comprising the ACS.
      METHODS AND RESULTS: Histological analysis demonstrated that epithelial NRP1
      expression increased significantly across the ACS (P = 0.0007), and correlated
      with microvessel density (MVD; r = 0.505, P = 0.0003) and weakly with VEGF (r =
      0.251, P = 0.001). In contrast, although NRP2 epithelial expression was increased
      significantly in all carcinomas (P < 0.002), there was no correlation with MVD,
      VEGF or NRP1. Furthermore, patients showing coexpression of NRP1 and NRP2 had a
      potentially worse prognosis than those expressing a single neuropilin or neither
      one. Although vascular expression of NRP1 increased significantly across the ACS
      (P = 0.0004) and correlated with MVD (r = 0.361, P = 0.0006), NRP2 vascular
      expression decreased significantly (P = 0.0001) and showed an inverse correlation
      with MVD (r=-0.506, P = 0.0001), suggesting differential roles for neuropilins in
      the angiogenic process during colorectal cancer development. CONCLUSIONS: These
      data suggest that an increase in NRP1 and NRP2 epithelial/tumour expression, as
      well as in NRP1 vascular expression, may be associated with disease progression
      in colorectal cancer.

PMID- 23551579
TI  - Benign cephalic histiocytosis: case report and review of the literature.
AB  - Benign cephalic histiocytosis (BCH) is a rare type of non-Langerhans histiocytic
      disorder, usually presenting with small, yellow-red or yellow-brown, asymptomatic
      papules, located mostly on the head and neck of infants and young children. The
      histopathologic hallmark of BCH is a well-circumscribed histiocytic infiltrate in
      the superficial to mid-reticular dermis. BCH is a self-healing disorder, with the
      eruptions regressing spontaneously in most cases; therefore no treatment is
      required. We present a case of BCH in a 7-month-old boy who was referred to our
      department with multiple, asymptomatic, yellow-red papules located on his face,
      and we review 55 cases published in the English-language literature in an effort
      to better describe and understand this unusual entity. 

PMID- 23551580
TI  - Association of micropapillary urothelial carcinoma of the bladder and BK viruria
      in kidney transplant recipients.
AB  - INTRODUCTION: BK virus (BKV) is an ubiquitous human polyomavirus that establishes
      latency in urothelium. BKV is known to re-activate in immunosuppressed
      individuals, and is an increasingly important cause of nephropathy and graft loss
      in kidney transplant recipients. Animal studies have demonstrated BKV has a
      potential role as a tumor virus. However, its role in precipitating or
      facilitating oncogenesis in humans is still debated. REPORT: We report 2 cases of
      aggressive micropapillary urothelial carcinoma of the bladder in kidney
      transplant recipients with persistent BK viruria and preserved graft function.
      RESULTS: In both cases, polyomavirus immunohistochemistry performed on the tumor
      specimens was strongly positive, and limited to the malignant tissue. BKV DNA,
      viral protein 1, and large T antigen mRNA were detected in the tumor; however, no
      viral particles were seen on electron microscopy. CONCLUSION: In one of the
      cases, BKV integration into the host genome was identified, leading to the
      truncation of the major viral capsid gene. This finding raises the concern that
      persisting BK viruria may be a risk factor for this aggressive form of bladder
      cancer. Further studies to determine screening and management strategies are
      required.

PMID- 23551581
TI  - Effect of surface modification on the bond strength between zirconia and resin
      cement.
AB  - PURPOSE: This study aimed to evaluate the micro push-out (MU-PO) bond strength
      between zirconia and resin cement after addition of zirconia particles to
      increase the surface roughness. MATERIALS AND METHODS: Y-TZP zirconia specimens
      in three experimental groups were subjected to Y-TZP particle deposition via
      dipping into the milling residue suspension at different times prior to the
      sintering process. The dipping procedure was repeated twice for each specimen in
      group B, six times in group C, and ten times in group D. The specimens subjected
      to airborne-particle abrasion (110 MUm Al2 O3, Rocatec Pre) acted as the control
      group (group A). All of the specimens were then bonded using adhesive resin
      cement (RelyX Ultimate). A MU-PO test was used to determine the bond strength
      values. One-way ANOVA at a 5% confidence level was performed for data analysis.
      Optical microscopy and scanning electron microscopy (SEM) were used to evaluate
      the failure modes and surface structure. RESULTS: Y-TZP particle deposition did
      not have a significant effect on the bond strength of the resin cement to
      zirconia specimens when compared to the control (p = 0.141). Higher bond strength
      values were observed in groups C and D than in control. The surface layer
      presented blister-like porosities with openings of various diameters ranging
      between 2 and 4 MUm. CONCLUSION: Y-TZP particle deposition after dipping six and
      ten times did not improve the mean bond strength statistically but presented
      surface topography that may be favorable for increased micromechanical retention
      for adhesive resin cement. CLINICAL SIGNIFICANCE: Y-TZP particle deposition may
      create a more retentive surface than airborne-particle abrasion for adhesive
      bonding between zirconia surface and resin cement.

PMID- 23551582
TI  - ALK rearrangements in EBUS-derived transbronchial needle aspiration cytology in
      lung cancer.
AB  - OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for
      anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully
      with the ALK inhibitor crizotinib. ALK copy-number abnormalities have also been
      described. In this study, we evaluated the suitability of fluorescence in situ
      hybridization (FISH) and immunohistochemistry (IHC) to determine ALK status in
      endobronchial ultrasound (EBUS)-derived cytology samples. METHODS: Samples were
      obtained from 55 consecutive patients with NSCLC who had undergone EBUS
      transbronchial needle aspiration (TBNA) according to our standard clinical
      protocols. All tumours had been screened previously for epithelial growth factor
      receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)
      mutations. FISH, using commercially available ALK rearrangement-specific probes,
      was employed to assess ALK status. IHC using the ALK-1 monoclonal antibody (DAKO)
      was also performed. RESULTS: FISH analysis was successful in 52 of 55 samples
      (94.5%); ALK rearrangement was demonstrated in 3 of 52 samples from patients with
      NSCLC (5.7%). ALK amplification was observed in 3 of 52 patient samples (5.7%)
      and an increase in ALK copy number was found in 28 of 52 patient samples (53.8%).
      IHC on cell blocks demonstrated ALK expression in one of three samples with ALK
      rearrangement. One patient sample had concomitant ALK rearrangement and KRAS
      mutation. CONCLUSIONS: We found FISH to be superior to IHC using the ALK-1
      monoclonal antibody for the detection of ALK rearrangement in EBUS-TBNA cytology
      specimens in NSCLC, and also that ALK rearrangement can co-exist with KRAS
      mutation in the same tumour.

PMID- 23551583
TI  - Sterols are required for cell-fate commitment and maintenance of the stomatal
      lineage in Arabidopsis.
AB  - Asymmetric cell division is important for regulating cell proliferation and fate
      determination during stomatal development in plants. Although genes that control
      asymmetric division and cell differentiation in stomatal development have been
      reported, regulators controlling the process from asymmetric division to cell
      differentiation remain poorly understood. Here, we report a weak allele (fk
      J3158) of the Arabidopsis sterol C-14 reductase gene FACKEL (FK) that shows
      clusters of small cells and stomata in leaf epidermis, a common phenomenon that
      is often seen in mutants defective in stomatal asymmetric division.
      Interestingly, the physical asymmetry of these divisions appeared to be intact in
      fk mutants, but the cell-fate asymmetry was greatly disturbed, suggesting that
      the FK pathway links these two crucial events in the process of asymmetric
      division. Sterol profile analysis revealed that the fk-J3158 mutation blocked
      downstream sterol production. Further investigation indicated that
      cyclopropylsterol isomerase1 (cpi1), sterol 14alpha-demethylase (cyp51A2) and
      hydra1 (hyd1) mutants, corresponding to enzymes in the same branch of the sterol
      biosynthetic pathway, displayed defective stomatal development phenotypes,
      similar to those observed for fk. Fenpropimorph, an inhibitor of the FK sterol C
      14 reductase in Arabidopsis, also caused these abnormal small-cell and stomata
      phenotypes in wild-type leaves. Genetic experiments demonstrated that sterol
      biosynthesis is required for correct stomatal patterning, probably through an
      additional signaling pathway that has yet to be defined. Detailed analyses of
      time-lapse cell division patterns, stomatal precursor cell division markers and
      DNA ploidy suggest that sterols are required to properly restrict cell
      proliferation, asymmetric fate specification, cell-fate commitment and
      maintenance in the stomatal lineage cells. These events occur after physical
      asymmetric division of stomatal precursor cells.

PMID- 23551584
TI  - Urinary incontinence in Emirati women with diabetes mellitus type 2: prevalence,
      risk factors and impact on life.
AB  - AIMS AND OBJECTIVES: To evaluate prevalence, risk factors for urinary
      incontinence and its impact on lives of Emirati women with diabetes mellitus type
      2 (DM2). Risk factors examined were age, parity, history of urinary tract
      infections, body mass index (BMI) and DM2 duration. BACKGROUND: Incontinence is a
      known complication of DM2 with impact on women's lives. Less is known about
      incontinence problem among Emirati women with DM2. DESIGN: A cross-sectional
      survey design using probability sampling approach was employed to assess urinary
      incontinence in Emirati women with DM2. METHODS: A total of 300 women with DM2,
      aged 20-65 years, were recruited from six healthcare centres. Data were collected
      over an 18-month period. A standardised incontinence questionnaire was used to
      assess type and frequency of incontinence within the past 12 months. Presence of
      weekly incontinence was the main outcome. RESULTS: Of the 300 women, 188 (63%)
      reported any incontinence, of which 48% had at least weekly episode. Both stress
      (n = 154, 51.3%) and urge (n = 181, 60.3%) were reported by participants, with 48
      (31.1%) reporting at least weekly stress and 85 (46.9%) expressing at least
      weekly urge incontinence. Diabetes duration was a significant risk factor for
      any, stress and urge incontinence followed by age for only any and stress
      incontinence. BMI was a risk factor for urge incontinence. Women perceived
      incontinence as bothersome, disturbing their social activities and daily prayers.
      CONCLUSIONS: The prevalence of incontinence in Emirati women with DM2 is higher
      than that reported by women in other cultures. Risk factors identified were DM2
      duration, age and obesity. Emirati women found incontinence to be a bothersome
      problem influencing their daily lives and prayers. RELEVANCE TO CLINICAL
      PRACTICE: Nurses in general practice should be alert to the incontinence problem
      by considering it as part of the routine diabetes evaluation of women, especially
      of those with longer duration of diabetes, obese and older. Cultural knowledge,
      sensitivity and individualised treatment plans need to be adopted by nurses
      working in the UAE to encourage the reporting of incontinence by Emirati Muslim
      women with DM2.

PMID- 23551585
TI  - Aesthetic correction of cicatricial sideburn alopecia using follicular-unit hair
      grafts.

PMID- 23551586
TI  - Nongrafted sinus floor elevation with a space-maintaining titanium mesh: case
      series study on four patients.
AB  - PURPOSE: Numerous materials and techniques have been introduced to augment the
      maxillary sinus floor for future dental implant placement. Schneiderian membrane
      tenting above simultaneously placed implants proved to be a successful technique.
      The present study investigated the use of a titanium micromesh for lateral-window
      sinus floor elevation without bone grafting. MATERIAL AND METHODS: Four patients
      indicated for two-stage sinus lifting were included. Through a lateral window, a
      titanium micromesh was tailored and placed into the sinus to maintain the
      elevated membrane in place. Immediate and 6-month postoperative cone beam
      computed tomography (CBCT) was performed to measure the gained bone height.
      During implant placement, bone core biopsies were retrieved for histomorphometry.
      RESULTS: The average residual ridge height among the eight sinuses was 3.6 mm +/-
      1.6 mm. Six months postoperatively, it reached 9.63 mm +/- 1.47 mm.
      Histomorphometry revealed that the average bone volume of the native bone was
      30.3% +/- 9.1%, while that of the newly formed bone was 55.3% +/- 11.4%.
      CONCLUSION: Within the limitations of this study due to the small sample size,
      the use of the titanium micromesh as a space-maintaining device after
      schneiderian membrane elevation is a reliable technique to elevate the floor of
      the sinus without grafting.

PMID- 23551587
TI  - Complications and adverse patient reactions associated with the surgical
      insertion and removal of palatal implants: a retrospective study.
AB  - OBJECTIVES: The purpose of this study was to assess the frequency and variety of
      surgical complications and adverse patient reactions associated with the
      implantation and explantation of palatal implants. MATERIALS AND METHODS: The
      implantations and explantations of palatal implants in 146 patients who had
      undergone orthodontic treatment using a palatal implant for anchorage in the time
      period 1999-2010 were evaluated retrospectively. All complications and adverse
      patient reactions associated with the surgical intervention of implantation and
      explantation of the implant were assessed. RESULTS: Of the 146 palatal implants
      reviewed, 104 implantations and 44 explantations met the inclusion criteria and
      their data could be extracted. Of the 104 implantations, 25 (24.0%) surgical
      complications and adverse patient reactions could be documented. They consisted
      of lack of primary stability: 7 (6.7%), prolonged pain: 7 (6.7%), secondary
      bleeding: 6 (5.8%), perforation of nasal floor: 2 (1.9%), necrotic mucosa
      anterior of the implant: 2 (1.9%) and sensory impairment of the anterior palate:
      1 (1%). The respective incidents for the 44 explantations were: disturbed wound
      healing: 3 (6.8%), perforation of nasal floor: 1 (2.3%), secondary bleeding: 1
      (2.3%) and fracture of the implant: 1 (2.3%). CONCLUSIONS: A wide spectrum of
      surgical complications and adverse patient reactions after palatal implant
      insertion and removal was found. All complications were of minor severity and
      duration except after one implantation, where a prolonged hypoesthesia of the
      anterior palate was found. Although only a small risk of a permanent sensory
      impairment of the anterior palatal region remains, patients must be well informed
      accordingly.

PMID- 23551588
TI  - The role of spreading depolarization in subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is a devastating disease associated with death and
      poor functional outcome. Despite decades of intense research and improvements in
      clinical management, delayed cerebral ischaemia (DCI) remains the most important
      cause of morbidity and mortality after SAH. The key role of angiographic cerebral
      vasospasm, thought to be the main cause of DCI, has been questioned. Emerging
      evidence suggests that DCI is likely to have a multifactorial etiology. Over the
      last few years, spreading depolarization (SD) has been identified as a potential
      pathophysiological mechanism contributing to DCI. The presence of cortical
      spreading ischaemia, due to an inverse hemodynamic response to SD, offers a
      possible explanation for DCI and requires more intensive research. Understanding
      the role of SD as another mechanism inducing DCI and its relationship with other
      pathological factors could instigate the development of new approaches to the
      diagnosis and treatment of DCI in order to improve the clinical outcome. 

PMID- 23551589
TI  - Phylum-wide general protein O-glycosylation system of the Bacteroidetes.
AB  - The human gut symbiont Bacteroides fragilis has a general protein O-glycosylation
      system in which numerous extracytoplasmic proteins are glycosylated at a three
      amino acid motif. In B. fragilis, protein glycosylation is a fundamental and
      essential property as mutants with protein glycosylation defects have impaired
      growth and are unable to competitively colonize the mammalian intestine. In this
      study, we analysed the phenotype of B. fragilis mutants with defective protein
      glycosylation and found that the glycan added to proteins is comprised of a core
      glycan and an outer glycan. The genetic region encoding proteins for the
      synthesis of the outer glycan is conserved within a Bacteroides species but
      divergent between species. Unlike the outer glycan, an antiserum raised to the
      core glycan reacted with all Bacteroidetes species tested, from all four classes
      of the phylum. We found that diverse Bacteroidetes species synthesize numerous
      glycoproteins and glycosylate proteins at the same three amino acid motif. The
      wide-spread conservation of this protein glycosylation system within the phylum
      suggests that this system of post-translational protein modification evolved
      early, before the divergence of the four classes of Bacteroidetes, and has been
      maintained due to its physiological importance to the diverse species of this
      phylum.

PMID- 23551590
TI  - Characterization of HLA-F polymorphism in four distinct populations in Mainland
      China.
AB  - Currently, there is a lack of information on polymorphism of human leucocyte
      antigen-F (HLA-F) gene in ethnically diverse human populations. In this study,
      HLA-F allelic typing was performed for 690 individuals representing two southern
      Chinese Han populations (Hunan Han and Guangdong Han) and two northern Chinese
      populations (Inner Mongolia Han and Inner Mongolia Mongol), using polymerase
      chain reaction-sequence-specific priming (PCR-SSP) and PCR-sequencing methods.
      Our results showed that (i) HLA-F*01 : 01 predominated in each population with a
      frequency >0.94 and HLA-F*01 : 03 was relatively more common in the two northern
      Chinese populations with a frequency of approximately 0.05; (ii) both
      geographical and ethnical factors are related to HLA-F allelic distribution, as
      evidenced by the significant difference in HLA-F allelic distribution between the
      Hunan Han population and the two northern Chinese populations; (iii) significant
      linkage disequilibrium (LD) was observed for haplotype HLA-A*03-F*01 : 03 in
      three populations. In most cases, this haplotype extended to HLA-E*01 : 03; and
      (iv) Ewens-Watterson homozygosity statistic at the HLA-F locus did not depart
      significantly from expectation in each of the four populations. Our data revealed
      a low level of HLA-F allelic variation in Chinese populations, suggesting that
      HLA-F gene may have existed before some of the HLA-A polymorphism and have been
      evolving under neutrality.

PMID- 23551591
TI  - Nerve injury-induced protein 1 (Ninjurin-1) is a novel therapeutic target for
      cavernous nerve injury-induced erectile dysfunction in mice.
AB  - INTRODUCTION: Radical prostatectomy for prostate cancer can not only induce
      cavernous nerve injury (CNI) but also result in structural changes in the
      cavernous tissues. Nerve injury-induced protein 1, Ninjurin-1 (Ninj1), is known
      to be involved in neuroinflammatory processes and to be related to vascular
      regression during the embryonic period. AIM: The study aims to determine whether
      and how Ninj1 neutralizing antibody (Ninj1-Ab) restores erectile function in mice
      with CNI. METHODS: Twelve-week-old C57BL/6J mice were used and distributed into
      four groups: sham operation group and CNI groups receiving a single
      intracavernous injection of immunoglobulin G (IgG) control antibody, low-dose
      Ninj1-Ab (1.0 MUg/20 MUL), or high-dose Ninj1-Ab (2.5 MUg/20 MUL). MAIN OUTCOME
      MEASURES: One week after bilateral cavernous nerve crush, erectile function was
      measured by electrical stimulation of the cavernous nerve. The penis was
      harvested for histologic examinations and Western blot analysis. RESULTS: The
      cavernous expression of Ninj1 protein was upregulated up to 7 days after CNI and
      returned to baseline levels thereafter. Local delivery of Ninj1-Ab significantly
      increased penile neuronal nitric oxide synthase and neurofilament contents,
      induced cavernous endothelial proliferation and phosphorylation of Akt and
      endothelial nitric oxide synthase, and decreased endothelial cell apoptosis in
      the CNI mice by upregulating angiopoietin-1 and downregulating angiopoietin-2.
      High-dose Ninj1-Ab induced profound restoration of erectile function in the CNI
      mice (91% of sham control values), whereas low-dose Ninj1-Ab elicited partial
      improvement. CONCLUSION: The dual neurotrophic and angiogenic effects of Ninj1
      blockade may provide a good opportunity for treating erectile dysfunction
      resulting from radical prostatectomy.

PMID- 23551592
TI  - Pneumatic dilation versus laparoscopic Heller myotomy for the treatment of
      achalasia: variables related to a good response.
AB  - Achalasia is a motor disorder characterized by esophageal aperistalsis and
      failure of lower esophageal sphincter relaxation. The cardinal symptoms are
      dysphagia, food regurgitation and weight loss. The most effective treatments are
      pneumatic dilation (PD) of the cardia and Heller esophageal myotomy with partial
      fundoplication. There is still controversy regarding which treatments should be
      initially done. The aims of this study were to evaluate clinical response and the
      variables related to good results in both treatments. Ninety-two patients with
      achalasia diagnosed by esophageal manometry were randomized to receive either PD
      or laparoscopic Heller myotomy with partial fundoplication. After the procedure,
      patients were followed up clinically and submitted to esophageal manometry and pH
      monitoring. Three months after treatment, 73% of the patients from PD group and
      84% of the surgery group had good results (P = 0.19). After 2 years of follow-up,
      54% of the PD group and 60% of the surgery group (P = not significant) were
      symptom free. Variables related to a good response to PD were a 50% drop in lower
      esophageal sphincter pressure (LESP) or a LESP <10 mmHg after treatment. Patients
      over 40 years old with LESP <=32 mmHg before treatment and a drop in LESP >50%
      after treatment significantly achieved better responses after surgical treatment
      when compared with PD. The reflux rate was significantly higher in the PD group
      (27.7%) compared with the surgery group (4.7%), P = 0.003. We concluded that
      surgical treatment and PD for achalasia are equally effective even after 2 years
      of follow-up. The choice of treatment for achalasia should be based on the
      following parameters: treatment availability, rate of good results, complication
      rates, variables related to good responses and also the patient's wish. 

PMID- 23551593
TI  - Phase II study of everolimus in metastatic urothelial cancer.
AB  - What's known on the subject? and what does the study add?: No recent advances
      have been made in the treatment of patients with advanced bladder cancer and, to
      date, targeted therapies have not resulted in an improvement in outcome. The
      mammalian target of rapamycin pathway has been shown to be up-regulated in
      bladder cancer and represents a rational target for therapeutic intervention. In
      the present phase II study of everolimus, one near-complete response, one partial
      response and several minor responses suggest that everolimus possesses biological
      activity in a subset of patients with bladder cancer. To maximize benefit from
      targeted agents such as everolimus, the preselection of patients based on
      molecular phenotype is required. OBJECTIVE: To assess the efficacy and
      tolerability of everolimus in advanced urothelial carcimoma (UC). PATIENTS AND
      METHODS: The present study comprised a single-arm, non-randomized study in which
      all patients received everolimus 10 mg orally once daily continuously (one cycle
      = 4 weeks). In total, 45 patients with metastatic UC progressing after one to
      four cytotoxic agents were enrolled between February 2009 and November 2010 at
      the Memorial Sloan-Kettering Cancer Center. The primary endpoints were 2-month
      progression-free survival (PFS) and the safety of everolimus, with the secondary
      endpoint being the response rate. A Simon minimax two-stage design tested the
      null hypothesis that the true two month PFS rate was <= 50%, as opposed to the
      alternative hypothesis of >= 70%. RESULTS: The most common grade 3/4 toxicities
      were fatigue, infection, anaemia, lymphopaenia, hyperglycaemia and
      hypophosphataemia. There were two partial responses in nodal metastases, with one
      patient achieving a 94% decrease in target lesions and remaining on drug at 26
      months. An additional 12 patients exhibited minor tumour regression. There were
      23 of 45 (51%) patients who were progression-free at 2 months with a median (95%
      CI) PFS of 2.6 (1.8-3.5) months and a median (95% CI) overall survival of 8.3
      (5.5-12.1) months. No clear association was observed between mammalian target of
      rapamycin pathway marker expression and 2-month PFS. CONCLUSIONS: Although
      everolimus did not meet its primary endpoint, one partial response, one near
      complete response and twelve minor regressions were observed. Everolimus
      possesses meaningful anti-tumour activity in a subset of patients with advanced
      UC. Studies aiming to define the genetic basis of everolimus activity in
      individual responders are ongoing.

PMID- 23551594
TI  - Shifting exudative age-related macular degeneration patients to ranibizumab after
      insufficient response to bevacizumab.

PMID- 23551595
TI  - Estimating extinction risk with metapopulation models of large-scale
      fragmentation.
AB  - Habitat loss is the principal threat to species. How much habitat remains-and how
      quickly it is shrinking-are implicitly included in the way the International
      Union for Conservation of Nature determines a species' risk of extinction. Many
      endangered species have habitats that are also fragmented to different extents.
      Thus, ideally, fragmentation should be quantified in a standard way in risk
      assessments. Although mapping fragmentation from satellite imagery is easy,
      efficient techniques for relating maps of remaining habitat to extinction risk
      are few. Purely spatial metrics from landscape ecology are hard to interpret and
      do not address extinction directly. Spatially explicit metapopulation models link
      fragmentation to extinction risk, but standard models work only at small scales.
      Counterintuitively, these models predict that a species in a large, contiguous
      habitat will fare worse than one in 2 tiny patches. This occurs because although
      the species in the large, contiguous habitat has a low probability of extinction,
      recolonization cannot occur if there are no other patches to provide colonists
      for a rescue effect. For 4 ecologically comparable bird species of the North
      Central American highland forests, we devised metapopulation models with area
      weighted self-colonization terms; this reflected repopulation of a patch from a
      remnant of individuals that survived an adverse event. Use of this term gives
      extra weight to a patch in its own rescue effect. Species assigned least risk
      status were comparable in long-term extinction risk with those ranked as
      threatened. This finding suggests that fragmentation has had a substantial
      negative effect on them that is not accounted for in their Red List category.

PMID- 23551597
TI  - Cellular origin and diagnostic significance of high-fluorescent cells in
      cerebrospinal fluid detected by the XE-5000 hematology analyzer.
AB  - INTRODUCTION: The Sysmex XE-5000 is a blood and body fluid analyzer able to
      differentiate cells into polymorphonuclear, mononuclear, and high-fluorescent
      cells (HFC). The identity of HFC in cerebrospinal fluid (CSF) has been uncertain;
      however, compatible with their high nucleic acid content, HFC could represent
      intrathecal tumor cells. Here, we studied the cellular origin and the diagnostic
      significance of HFC in CSF. METHODS: Results of CSF examinations with the XE-5000
      were analyzed in 65 CSF samples with and 126 CSF samples without tumor cells, as
      defined by manual microscopy of CSF cytospin preparations. RESULTS: The XE-5000
      detected HFC in 51 of 65 tumor cell-positive and in 33 of 126 tumor cell-negative
      CSF samples (sensitivity: 78.5%, specificity: 73.8%, positive likelihood ratio:
      3.0, negative likelihood ratio: 0.29). The percentages of HFC and tumor cells in
      CSF samples correlated (r2 = 0.41, P < 0.0001). Tumor cells escaped detection by
      the XE-5000 especially in CSF samples with a low percentage of tumor cells.
      CONCLUSION: While this study identifies tumor cells as the predominant correlate
      of HFC in CSF, it suggests that measuring HFC is not an appropriate diagnostic
      test for intrathecal tumor cells. However, if HFC are incidentally detected in
      CSF, further evaluation by CSF microscopy seems mandatory.

PMID- 23551596
TI  - Telocytes: new insight into the pathogenesis of gallstone disease.
AB  - The major mechanisms of gallstone formation include biliary cholesterol
      hypersecretion, supersaturation and crystallization, mucus hypersecretion, gel
      formation and bile stasis. Gallbladder hypomotility seems to be a key event that
      triggers the precipitation of cholesterol microcrystals from supersaturated
      lithogenic bile. Telocytes, a new type of interstitial cells, have been recently
      identified in many organs, including gallbladder. Considering telocyte functions,
      it is presumed that these cells might be involved in the signalling processes.
      The purpose of this study was to correlate the quantity of telocytes in the
      gallbladder with the lithogenicity of bile. Gallbladder specimens were collected
      from 24 patients who underwent elective laparoscopic cholecystectomy for
      symptomatic gallstone disease. The control group consisted of 25 consecutive
      patients who received elective treatment for pancreatic head tumours. Telocytes
      were visualized in paraffin sections of gallbladders with double
      immunofluorescence using primary antibodies against c-Kit (anti-CD117) and anti
      mast cell tryptase. Cholesterol, phospholipid and bile acid levels were measured
      in gallbladder bile. The number of telocytes in the gallbladder wall was
      significantly lower in the study group than that in the control group (3.03 +/-
      1.43 versus 6.34 +/- 1.66 cell/field of view in the muscularis propria, P <
      0.001) and correlated with a significant increase in the cholesterol saturation
      index. The glycocholic and taurocholic acid levels were significantly elevated in
      the control subjects compared with the study group. The results suggest that bile
      composition may play an important role in the reduction in telocytes density in
      the gallbladder.

PMID- 23551598
TI  - Bioinformatics analysis reveals potential candidate drugs for cervical cancer.
AB  - AIM: We sought to explore the mechanisms of cervical carcinoma response to
      epidermal growth factor (EGF), and then identify biologically active small
      molecules capable of targeting the sub-pathways that were dysregulated in
      cervical cancer cells in the response to EGF. MATERIAL AND METHODS:
      Differentially expressed genes and pathways were analyzed based on the
      transcription profile of GSE6783, and then the differentially expressed molecules
      were further analyzed by several bioinformatics methods. RESULTS: Our results
      suggested that EGF could promote cervical cancer cell proliferation through
      triggering the dysregulation of certain sub-pathways in the mitogen-activated
      protein kinase signaling pathway, p53 signaling pathway and pathways in cancer.
      Furthermore, our bioinformatics analysis revealed a total of 49 small molecules
      which may play a role in perturbing the response to EGF of cervical cancer cells.
      CONCLUSIONS: Candidate drugs identified by our approach may provide the
      groundwork for a combination therapy approach for cervical cancer; however,
      further studies are still needed to make sure that the use of parthenolide or
      other anti-cancer agents is effective without inhibiting important host defense
      mechanisms in cervical cancer.

PMID- 23551599
TI  - Salivary progesterone as a biochemical marker to predict early preterm birth in
      asymptomatic high-risk women.
AB  - OBJECTIVE: To evaluate salivary progesterone as a predictor of early preterm
      birth (PTB) and compare it with transvaginal sonographic (TVS) cervical length in
      asymptomatic high-risk women. DESIGN: Prospective study. SETTING: Departments of
      Obstetrics and Gynaecology and Biochemistry at UCMS & GTBH, Delhi, India. SAMPLE:
      Ninety pregnant women. METHODS: The progesterone concentration in saliva of
      asymptomatic pregnant women at high risk for preterm delivery was estimated by
      immunoassay, and cervical length was measured by TVS, at the first antenatal
      visit at 24-28 weeks of gestation, and then repeated 3-4 weeks later. MAIN
      OUTCOME MEASURES: Early PTB, mean and critical cut-off values of salivary
      progesterone, and a diagnostic value comparison of salivary progesterone with TVS
      cervical length. RESULTS: The mean value of salivary progesterone was
      significantly lower in all women who delivered at <37 weeks of gestation (n =
      38), compared with the term group (n = 52; P < 0.001). Salivary progesterone
      decreased significantly from the first to the second visit, with the maximum
      decrease observed in women who delivered at <34 weeks of gestation (29.6%, 95% CI
      17.8-41.4%, P < 0.002). The single predictive critical cut-off value for salivary
      progesterone was 2575 pg/ml, below which more than 80% of women delivered
      prematurely before 34 weeks of gestation, with sensitivity, specificity, and
      positive and negative predictive values of 83% (95% CI 58.6-96.4%), 86% (95% CI
      75.9-93.1%), 60% (95% CI 38.6-78.8%) and 95% (95% CI 87.1-99.0%), respectively.
      The TVS cervical length decreased significantly (P < 0.001) in the women who
      delivered prematurely. CONCLUSIONS: Low salivary progesterone concentration can
      be used for predicting early PTB in asymptomatic high-risk women.

PMID- 23551601
TI  - Comprehensive and rapid assessment of carotid plaques in acute stroke using a new
      single sweep method for three-dimensional carotid ultrasound.
AB  - We describe a 68-year-old man with acute stroke in whom the newly developed
      single sweep method for three-dimensional (3D) carotid ultrasound provided a
      rapid and comprehensive assessment of atherosclerotic plaque burden in the
      internal carotid artery. The two-dimensional duplex carotid scan diagnosed 50-69%
      stenosis, and with the three-dimensional method, the markedly hypoechogenic
      plaque (total volume 1.42 mL) was shown to occupy 77% of the total arterial
      volume (1.84 mL), consistent with severe lesion. The ultrasound findings were
      confirmed by computed tomographic angiography and subsequent carotid
      endarterectomy. The new single sweep 3D carotid ultrasound has the potential to
      become a valuable clinical tool in the assessment of stroke patients.

PMID- 23551602
TI  - Pediatric echocardiography: new developments and applications.
AB  - In this Special Issue of the Journal, 6 review articles that represent the new
      developments and applications of echocardiography for diagnosis and assessment of
      congenital heart disease from fetus to adult are included. The goal is to provide
      an updated review of the evidence for the current and potential use of some of
      the new methodologies, i.e. fetal echocardiography, tissue Doppler imaging,
      strain imaging by speckle tracking imaging, ventricular synchrony, quantification
      using real time three-dimensional (3D) echocardiography, and 3D echocardiography
      for adults with congenital heart disease. We hope this effort will provide an
      impetus for more investigation and ultimately clinical application of these new
      methodologies to improve the care of those with congenital and acquired heart
      diseases in the pediatric population and beyond.

PMID- 23551603
TI  - Advances in fetal echocardiography: early imaging, three/four dimensional
      imaging, and role of fetal echocardiography in guiding early postnatal management
      of congenital heart disease.
AB  - In this article, we review a number of topics that we believe reflect new and
      exciting aspects of fetal echocardiography. These new advances include early
      fetal cardiovascular imaging around 14 weeks, the utility of three/four
      dimensional imaging technology for the fetus, and finally the utility of fetal
      echocardiography for antenatal and perinatal care of congenital heart diseases to
      improve and optimize outcome. Finally, we briefly discussed future directions in
      fetal cardiac intervention.

PMID- 23551604
TI  - Tissue doppler myocardial velocity imaging in infants and children--a window into
      developmental changes of myocardial mechanics.
AB  - In adults, tissue Doppler myocardial velocity imaging (TDI) is a recommended
      component of routine echocardiography and particularly useful to assess diastolic
      function of the left ventricle. In contrast, color and pulsed-wave TDI velocities
      are less accepted in pediatrics, perhaps due to their strong age dependence in
      children. This review discusses the strengths and limitations of TDI velocity
      imaging in the pediatric age group. Myocardial velocities increase during normal
      childhood heart development, starting from fetal life, and these changes vary by
      cardiac segment. TDI velocity maturation opens an interesting window into the
      normal development of myocardial mechanics in childhood, but makes it difficult
      to interpret data in an individual child. Moreover, there is a wider range of
      normal for any given pediatric age than in adults. Still, TDI has been useful to
      monitor systolic heart function in children with cardiomyopathy or after heart
      transplantation. TDI studies revealed diastolic dysfunction in obese children and
      in cancer survivors with preclinical anthracycline cardiomyopathy. There is a
      growing body of studies using TDI to assess right heart function in children with
      congenital heart disease or pulmonary hypertension. Another potential strength of
      TDI velocities is the study of myocardial dyssynchrony where color TDI is well
      suited for rapid pediatric heart rates, even on fetal echocardiogram.
      Quantitative stress echocardiography with TDI is an emerging application in
      children that already offered insight into heart function in children with
      tetralogy of Fallot. Therefore, TDI velocity imaging should become part of the
      routine assessment of heart function in children.

PMID- 23551605
TI  - Speckle tracking echocardiography in pediatric and congenital heart disease.
AB  - Assessment of myocardial strain using speckle tracking echocardiography is an
      emerging echocardiographic technique that is increasingly used in the diagnosis
      and management of acquired heart disease in adults. In pediatric heart disease,
      this is still mainly considered as a research tool as the application of this
      technology has been slowed by the lack of vendor-independent technology and of
      normative data across the different age ranges. We believe that the technology
      has potential applications for the early detection of myocardial dysfunction, the
      quantification of ventricular function in congenital heart disease, and the
      detection of dyssynchrony.

PMID- 23551606
TI  - Echocardiographic assessment of ventricular synchrony in congenital and acquired
      heart disease in children.
AB  - Electromechanical dyssynchrony is an important consequence of and contributor to
      ventricular dysfunction. Echocardiography can be useful to assess the mechanisms
      underlying mechanical dyssynchrony, to evaluate the impact of mechanical
      dyssynchrony on ventricular function, and to try to predict the therapeutic
      response to cardiac resynchronization therapy (CRT). Mechanical dyssynchrony has
      been demonstrated in several pediatric acquired and congenital cardiac
      conditions, but experience is still limited. Moreover, the optimal method to
      identify dyssynchrony remains unclear, and data predicting the response to CRT in
      pediatrics are lacking. Understanding mechanisms of electromechanical
      dyssynchrony by echocardiography seems promising, at least in left bundle branch
      block (LBBB), but may be limited in children due to the uncommon occurrence of
      LBBB in this population. This review addresses the commonly used methods to
      diagnose mechanical dyssynchrony, discusses the emerging concepts on the
      mechanisms of the various types of mechanical dyssynchrony, and discusses the
      possible significance of mechanical synchrony in pediatric and acquired
      congenital heart disease.

PMID- 23551607
TI  - Real time three-dimensional echocardiography for quantification of ventricular
      volumes, mass, and function in children with congenital and acquired heart
      diseases.
AB  - Quantitative measurement of left ventricular (LV) volumes, mass, and function is
      one of the most common and important indications for echocardiography. These
      measurements are among the most powerful tools for diagnosis and prognosis of
      congenital and acquired heart diseases and for assessment of medical,
      percutaneous, and surgical interventions. Awareness is also growing of the
      importance of right ventricular (RV) volume, mass, and function in many
      cardiopulmonary diseases. Furthermore, there are challenges and opportunities to
      measure the volume, mass, and function of complex chambers such as the left
      atrium, right atrium, and the univentricular heart. As echocardiography continues
      to be the imaging modality of choice for these measurements, the strengths and
      limitations of M-mode, two-dimensional (2D), and recently three-dimensional (3D)
      echocardiographic (3DE) methodologies for accurate and reproducible measurement
      of these indices have been extensively investigated for congenital and acquired
      heart diseases. Evidence suggests that 3DE provides improved accuracy and
      reproducibility over 2D methods for measurement of LV volume and function
      calculation in adults and in children. Data have accumulated on the utility of
      3DE for measuring chamber volumes and function for the RV and for the single
      ventricle, which may become more widely used in clinical and research arenas in
      the future. Finally, new advanced modes of analysis such as 3D strain and
      synchrony analysis by 3DE are promising methodologies that warrant further
      investigation.

PMID- 23551608
TI  - The incremental value of three-dimensional transthoracic echocardiography in
      adult congenital heart disease.
AB  - Imaging with echocardiography is useful in diagnosing congenital heart disease
      (CHD). Two-dimensional (2D) transthoracic echocardiography (TTE) has been the
      standard cardiac imaging modality, but it forces the reader to mentally create
      the three-dimensional (3D) cardiac anatomy to understand these complex diseases.
      3D TTE, which has relatively recently emerged to address this limitation, is
      capable of providing clear and dynamic 3D views of these anatomic defects and
      offers more insight on how to manage them. This review article will address the
      benefit of utilizing 3D TTE for proper characterization of different types of CHD
      in the adult and as a guide to appropriate treatment.

PMID- 23551609
TI  - In memoriam, Ivan D'Cruz, M.D., senior associate editor and editor.

PMID- 23551612
TI  - Contrast-enhanced transrectal ultrasonography: measurement of prostate cancer
      tumor size and correlation with radical prostatectomy specimens.
AB  - OBJECTIVES: To determine the accuracy of contrast-enhanced transrectal
      ultrasonography for tumor size measurements of hypoechoic prostate cancer foci
      located in the peripheral zone. METHODS: A total of 55 men scheduled for radical
      prostatectomy, with biopsy-proven cancer in hypoechoic foci located in the
      peripheral zone, were consecutively enrolled in the present prospective study.
      Each patient underwent grayscale ultrasound and contrast-enhanced transrectal
      ultrasonography of the prostate according to a standardized protocol. The maximum
      tumor diameter on grayscale imaging and contrast-enhanced transrectal
      ultrasonography was compared with that determined using histopathology. RESULTS:
      A mean underestimation was documented to be approximately 3.9 mm and 0.6 mm for
      grayscale and contrast-enhanced transrectal ultrasonography imaging,
      respectively. Grayscale and contrast-enhanced transrectal ultrasonography imaging
      underestimated measurements by 76.67% (46 of 60) and 48.33% (29 of 60), whereas
      overestimated measurements were 20% (12 of 60) and 26.67% (16 of 60),
      respectively. A strong correlation was observed between contrast-enhanced
      transrectal ultrasonography and histopathological measurements (r = 0.91, P <
      0.0001). A weak linear correlation was found between grayscale and
      histopathological measurements (r = 0.59, P < 0.0001). Bland-Altman analysis
      results were in complete accordance with correlation analysis results. For cases
      with maximum histopathological tumor diameters <=10 mm and >10 mm, 40% (6 of 15)
      and 86.67% (39 of 45) were index tumors, respectively (P < 0.0001). CONCLUSIONS:
      Contrast-enhanced transrectal ultrasonography is significantly more accurate than
      conventional grayscale imaging for measuring prostate tumor size, especially for
      tumors with a diameter >10 mm, and it might have a role in preoperative
      assessment of prostatic index tumor sizes.

PMID- 23551613
TI  - Feasibility of mitral isthmus and left atrial roof linear lesions using an 8 mm
      tip cryoablation catheter.
AB  - BACKGROUND: Left atrial linear lesions are part of the ablation strategy for
      persistent atrial fibrillation. Radiofrequency (RF) energy is the standard energy
      modality. Pulmonary vein (PV) balloon cryoablation has similar success rates to
      RF energy but is unsuitable for linear lesions. This study assessed the
      feasibility and safety of left atrial linear lesions using an 8 mm tip
      cryoablation catheter. METHODS AND RESULTS: Consecutive patients undergoing left
      atrial ablation procedures for paroxysmal or persistent atrial fibrillation were
      studied. An 8 mm tip focal cryoablation catheter was used to create mitral
      isthmus and left atrial roof linear lesions and compared to a matched cohort
      undergoing RF ablation. A total of 21 patients (54 +/- 11 years, 14 male), 15
      undergoing de novo procedures using a dual console technique (simultaneous focal
      catheter and cryoballoon PV ablation) and 6 redo procedures (single console and
      focal catheter) were studied. Mitral isthmus ablation was successful in 19/21
      (91%) with a mean total ablation time of 32.5 +/- 2.9 minutes. Roof line ablation
      was successful in 18/19 with a mean ablation time of 15.6 +/- 6.0 minutes.
      Success rates were similar but ablation times were longer than those in the
      matched RF group. Epicardial ablation in the coronary sinus was required less
      often with cryoablation (11/21 vs 17/21, P < 0.05). There were no complications.
      CONCLUSION: Left atrial linear lesions with an 8 mm tip cryoablation catheter are
      feasible and safe with a high acute success rate. The need for coronary sinus
      ablation is reduced. A dual console technique is possible. Long-term durability
      of linear lesions remains to be determined.

PMID- 23551614
TI  - Symptom self-management strategies in patients with non-metastatic prostate
      cancer.
AB  - AIMS AND OBJECTIVES: To explore the association between symptoms, symptom
      distress and symptom self-management and to identify effective strategies of
      symptom self-management in men with non-metastatic prostate cancer following
      radical prostatectomy or radiation therapy. BACKGROUND: Men receiving treatments
      for localised prostate cancer experience symptoms of urinary incontinence,
      urinary obstruction/irritation, bowel difficulties and sexual dysfunction.
      Understanding patients' symptom experiences and identifying strategies that they
      use to manage these symptoms are imperative for symptom management planning.
      DESIGN: A descriptive, cross-sectional study was conducted with a sample of 53
      men, who were within three months of the initiation of their treatment. METHODS:
      The Symptom Indexes and the Strategy and Effectiveness of Symptom Self-Management
      questionnaires were used to measure symptoms, symptom distress and symptom self
      management. Descriptive statistics, t-tests, correlations and multiple
      regressions were used to analyse the data. RESULTS: Symptoms were significantly
      correlated with symptom-related distress (r = 0.67, p < 0.01). Frequency of
      symptoms was significantly associated with symptom self-management strategies for
      urinary (beta = 0.50, p < 0.01), bowel (beta = 0.71, p < 0.01) and sexual
      problems (beta = 0.28, p = 0.05). The most effective strategies were as follows:
      pads and doing Kegel exercise for managing urinary problems, rest and endurance
      for bowel symptoms, and expressing feelings and finding alternative ways to
      express affection for management of sexual dysfunction. CONCLUSIONS: Assessing
      symptom self-management among men with newly diagnosed prostate cancer can help
      healthcare providers develop strategies that will enhance health-related quality
      of life. RELEVANCE TO CLINICAL PRACTICE: Results provide information on effective
      strategies that patients with prostate cancer found to reduce their symptoms. The
      strategies used provide a foundation for developing and testing interventions for
      personalised symptom management.

PMID- 23551615
TI  - Metanephric adenoma and solid variant of papillary renal cell carcinoma: common
      and distinctive features.
AB  - AIMS: To evaluate morphological and immunohistochemical (IHC) features helpful in
      distinguishing metanephric adenoma (MA) from solid papillary renal cell carcinoma
      (s-PRCC). METHODS AND RESULTS: We present a detailed study of 21 MA and 23 s
      PRCC. The two entities exhibited significant similarities, both being well
      circumscribed tumours composed of tightly packed small cells arranged in solid
      sheets or ill-defined tubules, often presenting glomeruloid bodies, psammoma
      bodies and dystrophic calcification, and showing overlapping immunoreactivity for
      S100, CD57 and CK7. Conversely, most MA were non-encapsulated, whereas most s
      PRCC showed a thick fibrous pseudocapsule; MA cells had scanty cytoplasm and a
      high nuclear:cytoplasmic ratio in comparison to s-PRCC, where occasional tumour
      cells showed abundant cytoplasm and high nuclear grade. Polypoid branching fronds
      were common in MA, but absent in s-PRCC; multifocality and papillary
      hyperplasia/adenoma were seen only in s-PRCC. MA were positive for WT1 and
      negative for EMA and alpha-methylacyl-CoA racemase (AMACR); s-PRCC were positive
      for EMA and AMACR and negative for WT1. CONCLUSIONS: Despite overlapping
      features, careful morphological and architectural evaluation should result in
      accurate diagnosis of most MA and s-PRCC. In challenging cases, IHC stains for
      WT1, EMA and AMACR may help in distinguishing these two entities.

PMID- 23551616
TI  - Regulation of ICAM-1 expression in gingival fibroblasts infected with high
      glucose-treated P. gingivalis.
AB  - Porphyromonas gingivalis is a major pathogen in the initiation and progression of
      periodontal disease, which is recognized as a common complication of diabetes.
      ICAM-1 expression by human gingival fibroblasts (HGFs) is crucial for regulating
      local inflammatory responses in inflamed periodontal tissues. However, the effect
      of P. gingivalis in a high-glucose situation in regulating HGF function is not
      understood. The P. gingivalis strain CCUG25226 was used to study the mechanisms
      underlying the modulation of HGF ICAM-1 expression by invasion of high-glucose
      treated P. gingivalis (HGPg). A high-glucose condition upregulated fimA mRNA
      expression in P. gingivalis and increased its invasion ability in HGFs. HGF
      invasion with HGPg induced increases in the expression of ICAM-1. By using
      specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the
      activation of p38 MAPK and Akt pathways is critical for HGPg-induced ICAM-1
      expression. Luciferase reporters and chromatin immunoprecipitation assays suggest
      that HGPg invasion increases NF-kappaB- and Sp1-DNA-binding activities in HGFs.
      Inhibition of NF-kappaB and Sp1 activations blocked the HGPg-induced ICAM-1
      promoter activity and expression. The effect of HGPg on HGF signalling and ICAM-1
      expression is mediated by CXC chemokine receptor 4 (CXCR4). Our findings identify
      the molecular pathways underlying HGPg-dependent ICAM-1 expression in HGFs,
      providing insight into the effect of P. gingivalis invasion in HGFs. 

PMID- 23551617
TI  - Diet shapes the ability of human intestinal microbiota to degrade phytate--in
      vitro studies.
AB  - AIMS: Investigation of intestinal bacterial groups involved in phytate
      degradation and the impact of diets with different phytate contents on phytase
      activity. METHODS AND RESULTS: Faecal samples of adults on conventional (n = 8)
      or vegetarian (n = 8) diets and breastfed infants (n = 6) were used as an
      inoculum for modified media supplemented with phytate. Populations of Gram
      positive anaerobes (GPA), lactic acid bacteria (LAB), Proteobacteria-Bacteroides
      (P-B), coliforms and anaerobes were studied. The PCR-DGGE analysis revealed a
      random distribution of DGGE profiles in the dendrograms of GPA, P-B and
      coliforms, and a partially diet-specific distribution in the DGGE dendrograms of
      LAB and anaerobes. The degradation of phytic acid (PA) was determined with HPLC
      method in supernatants of the cultures. Regardless of the diet, the Gram-positive
      anaerobes and LAB displayed the lowest ability to degrade phytate, whereas the
      coliforms and P-B cultures produced higher amounts of intermediate myo-inositol
      phosphates. Bacterial populations grown in a nonselective medium were the most
      effective ones in phytate degradation. It was the vegetarians' microbiota that
      particularly degraded up to 100% phytate to myo-inositol phosphate products lower
      than InsP3. CONCLUSIONS: A diet rich in phytate increases the potential of
      intestinal microbiota to degrade phytate. The co-operation of aerobic and
      anaerobic bacteria is essential for the complete phytate degradation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insights on the effect
      of diet on specific metabolic activity of human intestinal microbiota.

PMID- 23551618
TI  - Isolated liver metastases in an adenoid cystic carcinoma of the submandibular
      gland on fine needle aspiration cytology: an unusual presentation.

PMID- 23551619
TI  - MALDI mass spectrometry-assisted molecular imaging of metabolites during nitrogen
      fixation in the Medicago truncatula-Sinorhizobium meliloti symbiosis.
AB  - Symbiotic associations between leguminous plants and nitrogen-fixing rhizobia
      culminate in the formation of specialized organs called root nodules, in which
      the rhizobia fix atmospheric nitrogen and transfer it to the plant. Efficient
      biological nitrogen fixation depends on metabolites produced by and exchanged
      between both partners. The Medicago truncatula-Sinorhizobium meliloti association
      is an excellent model for dissecting this nitrogen-fixing symbiosis because of
      the availability of genetic information for both symbiotic partners. Here, we
      employed a powerful imaging technique - matrix-assisted laser
      desorption/ionization (MALDI)/mass spectrometric imaging (MSI) - to study
      metabolite distribution in roots and root nodules of M. truncatula during
      nitrogen fixation. The combination of an efficient, novel MALDI matrix [1,8
      bis(dimethyl-amino) naphthalene, DMAN] with a conventional matrix 2,5
      dihydroxybenzoic acid (DHB) allowed detection of a large array of organic acids,
      amino acids, sugars, lipids, flavonoids and their conjugates with improved
      coverage. Ion density maps of representative metabolites are presented and
      correlated with the nitrogen fixation process. We demonstrate differences in
      metabolite distribution between roots and nodules, and also between fixing and
      non-fixing nodules produced by plant and bacterial mutants. Our study highlights
      the benefits of using MSI for detecting differences in metabolite distributions
      in plant biology.

PMID- 23551620
TI  - Clinicopathologic features of primary Merkel cell carcinoma: a detailed
      descriptive analysis of a large contemporary cohort.
AB  - BACKGROUND: Little uniformity exists in the clinical and histologic variables
      reported with primary Merkel cell carcinoma (MCC). OBJECTIVE: To provide a
      rigorous descriptive analysis of a contemporary cohort and promote the
      prospective collection of detailed data on MCC for future outcome studies.
      METHODS AND MATERIALS: A detailed descriptive analysis was performed for clinical
      and histologic features of 147 patients with 150 primary MCC tumors in a
      prospectively collected database from 2006 to 2010. RESULTS: The majority (73.5%)
      of patients were at American Joint Committee on Cancer clinical stage I or II at
      presentation, 20.4% at stage III, and 6.1% at stage IV. Detailed descriptive
      clinical and histologic findings are presented. CONCLUSION: Clinical and
      histologic profiling of primary MCC in the literature is variable and limited.
      Systematic prospective collection of MCC data is needed for future outcome
      studies and the ability to compare and share data from multiple sources for this
      relatively rare tumor.

PMID- 23551621
TI  - Body mass index in adult patients with diet-treated phenylketonuria.
AB  - BACKGROUND: There is an increasing number of adults with phenylketonuria (PKU) on
      a low phenylalanine diet. In the general population, an increasing body mass
      index (BMI) in the UK is a major problem with associated co-morbidities. The
      present study aimed to identify whether patients with diet-treated PKU have
      obesity rates comparable to those in the general population. METHODS: Two hundred
      and thirty-six PKU subjects (49% male, 51% female), aged >16 years, who were
      diagnosed by newborn screening and were receiving a low phenylalanine diet, were
      identified from seven metabolic centres in the UK. Retrospective data were
      collated on age, sex, BMI and mean phenylalanine concentration over the previous
      12 months. RESULTS: Mean (SD) phenylalanine concentration for all 236 subjects
      was 789 (311) MUm; mean (SD) BMI was 26 (5.4) kg m(-2) [males 25 (4.3) kg m(-2) ,
      females 27 (6.2) kg m(-2) ]; mean (SD) age was 26 (7) years; and 55% had a BMI >
      25 kg m(-2) . The percentage of subjects with a BMI >25 kg m(-2) and >30 kg m(-2)
      , as well as increasing obesity with age, was similar to the UK population. A
      correlation was observed between increasing BMI and a higher phenylalanine
      concentration (r = 0.243, P = 0.001). CONCLUSIONS: The number of overweight and
      obese patients with diet-treated PKU in the UK is a concern. This could lead to
      other obesity-related complications increasing the complexity of diet and the
      cost of their care. There is a need to educate patients with respect to adopting
      a healthy, low phenylalanine diet and lifestyle to prevent further rises in BMI.

PMID- 23551622
TI  - Adherence to initial PDE-5 inhibitor treatment: randomized open-label study
      comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in
      patients with erectile dysfunction.
AB  - INTRODUCTION: Phosphodiesterase type 5 (PDE-5) inhibitor treatment for erectile
      dysfunction (ED) is frequently discontinued; adherence may vary depending on the
      initial regimen. AIM: To evaluate the effects of initiating treatment with
      tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or
      sildenafil PRN on treatment adherence. METHODS: In this multicenter, open-label
      study, men (>= 18 years) with ED, naive to PDE-5 inhibitors, were randomized
      (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8
      week randomized treatment (RT) period (dose adjustment possible) was succeeded by
      16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed). MAIN
      OUTCOME MEASURES: Treatment adherence was measured as time to discontinuation of
      RT (any cause), estimated by Kaplan-Meier product-limit method. Treatment-group
      differences were estimated as hazard ratio (HR; Cox proportional hazards).
      RESULTS: Seven hundred seventy patients (mean age 53 years) were randomized to
      tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261).
      Kaplan-Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%,
      respectively. Median time to discontinuation of RT was significantly longer for
      tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR
      [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001).
      Reasons for discontinuation with significant differences between groups (P <
      0.05) included "lack of efficacy (duration of erection)" (sildenafil 9.2% vs.
      tadalafil OaD 4.3%, PRN 2.8%), "time constraints due to short window of action"
      (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and "feel medication controls
      my sexual life" (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group
      differences were found in International Index of Erectile Function-Erectile
      Function domain change from baseline to end of RT (least squares mean: 9.4-10.0,
      P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common
      adverse event (>= 4%) was headache. CONCLUSIONS: ED patients assigned to
      tadalafil OaD or PRN adhered significantly longer to initial treatment than
      patients assigned to sildenafil PRN. Improvement of erectile function and safety
      profiles were similar in all three treatment groups.

PMID- 23551623
TI  - Immediately loaded platform-switched implants in the anterior mandible with fixed
      prostheses: a randomized, split-mouth, masked prospective trial.
AB  - BACKGROUND: Platform-switched implants have been demonstrated to maintain
      marginal bone-level stability after immediate loading. The present study
      evaluated crestal bone loss and soft tissue stability around ANKYLOS plus(r)
      implants (A-implants) and Certain(r) PREVAIL(TM) (B-implants). MATERIALS AND
      METHODS: Patients were identified to receive three A- or three B-implants on each
      side of their mandibles, with randomization. All implants were loaded immediately
      after their insertion and splinted with a cemented provisional prosthesis. Final
      prostheses were delivered 3 months after implantation. Peri-implant crestal bone
      loss, gingival recession, and other soft tissue changes were evaluated throughout
      a 2-year follow-up. RESULTS: A total of one hundred seven implants were placed in
      18 patients. Two of the group A-implants and one group B-implant failed. At the
      final 24-month assessment, bone loss of at least 2 mm (mesially or distally) was
      recorded at 5 of the 44 surviving A-implants (11%) and 33 of the 47 B-implants
      (70%), a success rate of 88.63% for the A- and 29.78% for the B-implants.
      CONCLUSIONS: Significant changes in the level of the crestal bone loss around
      immediately loaded platform-switched dental implants seem to be related to the
      platform shape and size, as well as the implant-abutment connection, when
      abutments are not removed.

PMID- 23551624
TI  - High susceptibility to pemphigus vulgaris due to HLA-DRB1*14:54 in the Slovak
      population.
AB  - The current work describes an association between pemphigus vulgaris (PV) and
      class II HLA alleles in the Slovak population, the first such study in Slovakia
      on the 'high-resolution level'. This work takes into account the new HLA allele
      nomenclature, officially adopted in 2010. In particular, we have focused on the
      associations between PV and DRB1*14:54 and DRB1*14:01. This case-control study
      was performed in a cohort of 43 PV Caucasian patients and 113 Caucasian control
      subjects from Slovakia. HLA typing was performed using PCR-SSP (polymerase chain
      reaction with sequence-specific primers). We found significantly positive
      associations between PV and the HLA alleles DRB1*04:02, DRB1*04:04, DRB1*14:54,
      DRB1*14:04, DRB1*14:05, DQB1*03:02 and DQB1*05:03. In contrast, HLA-DQB1*06,
      DRB1*07 and DRB1*13 were negatively associated with PV. Importantly, 93% of PV
      patients possessed at least one of two HLA haplotypes, DRB1*04-DQB1*03 or HLA
      DRB1*14-DQB1*05. We confirmed the previously reported associations between HLA
      class II alleles and PV and described a new association between PV and
      DRB1*14:54. This allele was first described in 2005, and there has been only one
      report of its association with PV to date. 

PMID- 23551625
TI  - Immunohistochemical analysis on potential new molecular targets for esophageal
      cancer.
AB  - Despite multimodal therapeutic options, esophageal cancer is still among the most
      deadly malignancies. In the past decade, targeted therapy has shown great
      potential in other cancers, but data on esophageal carcinoma are still rare. Five
      potential new molecular targets in esophageal adenocarcinoma (EAC) and esophageal
      squamous cell carcinoma (ESCC) were investigated for their expression
      characteristics: vascular endothelial growth factor receptor (VEGFR)-3, human
      epidermal growth factor receptor-2, stem cell growth factor receptor, tissue
      inhibitors of metalloproteinase (TIMP)-4 and TIMP-3. One hundred seventy-one EAC
      and ESCC tissue samples obtained from patients undergoing esophagectomy from 2000
      to 2008 were included. Clinical data were evaluated retrospectively.
      Immunohistochemical staining was performed using tumor tissue with and without
      neoadjuvant treatment and healthy tissue. For samples without neoadjuvant
      treatment, expression of all targets was higher in tumor tissue than in healthy
      tissue except for VEGFR-3 (>98% expression in both tissues). For TIMP-4, TIMP-3
      and stem cell growth factor receptor, trends to higher expression in tumor tissue
      were also found in EAC and ESCC that had received neoadjuvant treatment. Using
      Matched-pair analysis, we compared target expression in tumor tissue with and
      without neoadjuvant treatment. Only TIMP-3 had significantly lower expression in
      neoadjuvant treated tumor tissue (EAC: P = 0.059, ESCC: P = 0.006). TIMP-4, TIMP
      3 and VEGFR-3 appear to qualify for targeted therapy in esophageal cancer because
      of their high expression in neoplastic tissue. TIMP-3 appears to be downregulated
      in neoadjuvantly treated esophageal cancer, and VEGFR-3 shows high expression in
      healthy mucosa leading to severe side effects by molecular targeting. Thus, TIMP
      4 seems the most promising target. 

PMID- 23551626
TI  - Heart failure options broaden.

PMID- 23551627
TI  - From infection to colonization: the role of microbiota in transplantation.

PMID- 23551628
TI  - Call it BOS, call it CLAD--the need for prospective clinical trials and
      elucidating the mechanism of extracorporeal photopheresis.

PMID- 23551629
TI  - Prolonged posttransplant survival with treatment of depressive symptoms.

PMID- 23551630
TI  - Too aggressive or not aggressive enough? Should a metric change center practice?

PMID- 23551631
TI  - A novel mutation of the ornithine transcarbamylase gene leading to fatal
      hyperammonemia in a liver transplant recipient.
AB  - Ornithine transcarbamylase (OTC) deficiency (OTCD) is an X-linked urea cycle
      disorder. Being an X-linked disease, the onset and severity of the disease may
      vary among female carriers. Some of them start to develop the disease early in
      life, whereas others remain asymptomatic throughout their lives. Our patient was
      a 42-year-old man who developed severe hyperammonemia and fatal brain edema after
      receiving a right lobe graft from an asymptomatic female living donor with
      unrecognized OTCD. The donor developed hyperammonemia and disturbed level of
      consciousness that was managed successfully by hemodialysis. Molecular testing of
      the OTC gene in the donor revealed a heterozygous nonsense mutation (c.429T>A) in
      exon 5.

PMID- 23551633
TI  - Jaundice six months following liver transplantation.

PMID- 23551634
TI  - Visceral varicella zoster virus infection after allogeneic stem cell
      transplantation.
AB  - INTRODUCTION: Varicella zoster virus (VZV) disease is one of the major infectious
      complications that can occur after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). Many reports have shown visceral VZV infection, a
      special type of VZV disease, to be rare. However, few studies so far have
      included a large number of patients. FINDINGS: Visceral VZV infection was found
      in 20 (0.8%) of 2411 patients who underwent allo-HSCT at our hospitals. Seventeen
      (85%) patients were taking immunosuppressive agents at the time of presentation
      with zoster. The presenting symptom was abdominal pain in 16 patients (80%),
      unconsciousness in 3 patients (15%), and no symptoms in 1 patient. The mean time
      interval from allo-HSCT to symptomatic visceral VZV infection was 273 days (103
      800 days). The eruptions appeared within 3 days (0-13) after the first symptoms.
      Treatment with intravenous acyclovir was initiated before the appearance of
      eruptions in 3 of 18 patients (all 3 survived) with vesicular eruptions, the same
      day in 12 patients (11 survived, 1 died), and after the appearance in 3 patients
      (1 survived, 2 died). The overall mortality was 20%. CONCLUSION: In conclusion,
      these data confirm that the incidence of visceral VZV infection is infrequent,
      but this disease is serious. When patients being treated with immunosuppressive
      agents demonstrate abdominal pain or unconsciousness, the possibility of visceral
      VZV infection should be considered as well as earlier therapeutic intervention.

PMID- 23551635
TI  - Corneal tattooing method using dye injection into the anterior stroma infiltrated
      with small air bubbles.

PMID- 23551636
TI  - Feasibility and oncological outcomes of laparoscopic treatment for local relapse
      of renal cell carcinoma.
AB  - What's known on the subject? and what does the study add?: Local relapse of renal
      cell carcinoma following radical nephrectomy is rare, and surgical removal
      provides the only opportunity for cure. Open surgery has been established as the
      usual approach for these tumours. It is, however, associated with significant
      morbidity. Our study describes the largest series of laparoscopic treatment of
      local relapse of renal cell carcinoma with the longest follow-up. We show that
      the laparoscopic approach is feasible in expert centres. It provides faster
      recovery and fewer complications with satisfactory oncological outcomes in
      selected patients. OBJECTIVE: To assess the feasibility and oncological outcomes
      of laparoscopic treatment for local relapse of renal cell carcinoma. PATIENTS AND
      METHODS: Nine patients were treated by a pure laparoscopic approach for local
      recurrence of a renal tumour between 2005 and 2011 by a single surgeon (HB),
      following an initial open radical nephrectomy for the primary tumour. Clinical
      and histopathological data were collected prospectively and analysed
      retrospectively. Seven patients were treated by a transperitoneal approach and
      two patients had a retroperitoneal approach. RESULTS: Relapse occurred within a
      mean time of 83 months (7-168) following nephrectomy. Recurrent tumour size
      varied from 2.5 to 4.5 cm. All surgeries were performed laparoscopically without
      need for conversion. Mean operative duration was 144 min (40-240), mean estimated
      blood loss was 430 mL (50-1300) and mean hospital stay was 4.5 days (3-6). Three
      patients had Clavien grade I intraoperative complications. Late complications
      were noted in two patients (Clavien I and IIIb). Pathology confirmed clear cell
      carcinoma in all patients with an absence of sarcomatoid features and negative
      surgical margins. Three patients had neoadjuvant treatment and two patients had
      adjuvant treatment. In all, 67% of patients were disease free with a mean follow
      up period of 3 years. CONCLUSIONS: Surgical removal of isolated local recurrence
      remains the only possibility of cure in patients with renal cell carcinoma. We
      demonstrated that the laparoscopic approach is a safe and feasible alternative
      treatment option for selected cases with low morbidity and satisfactory
      oncological outcomes.

PMID- 23551637
TI  - High-grade vaginal intraepithelial neoplasia: can we be selective about who we
      treat?
AB  - OBJECTIVE: To determine the role of conservative management in high-grade vaginal
      intraepithelial neoplasia (HG VaIN). DESIGN: Retrospective observational study.
      SETTING: Northern Gynaecological Oncology Centre, Gateshead, UK. POPULATION: A
      total of 100 women with histologically-proven HG VaIN. METHODS: Review of patient
      records from 1995 to 2011. MAIN OUTCOME MEASURES: Rates of progression to cancer,
      treatment remission, and disease recurrence, particularly post-treatment when
      vaginoscopy is normal but cytology is abnormal. RESULTS: Of 100 women referred,
      69 underwent initial treatment of whom 47 (68%) went into remission: of these,
      seven developed a recurrence after a median follow-up of 29 months (range 15-214
      months). Of the 31 women managed conservatively with cytological and vaginoscopic
      surveillance, no cancers developed after a median follow-up of 35 months (range 2
      230 months). Rate of overall progression to cancer was 3% and all were detected
      among the initial treatment group after a median of 59 months (range 8-249
      months). Post-treatment, when normal vaginoscopy was accompanied by abnormal
      cytology, two categories existed. Of 24 cases with low-grade cytological
      abnormality, recurrence of HG VaIN occurred in seven (29%) after a median follow
      up of 12 months (range 2-110 months). Of 19 cases with HG cytological
      abnormality, 15 (79%) developed recurrence at a median follow-up of 7 months
      (range 2-21 months), giving a hazard ratio 5.6 (95% confidence interval 2.0-15.5,
      P = 0.001). CONCLUSIONS: It is possible to select women with HG VaIN for
      conservative surveillance with excellent results. The majority of women
      undergoing initial treatment will enter remission. Post-treatment, if cytological
      abnormality develops in the presence of normal vaginoscopy, the majority of women
      will develop histological HG VaIN recurrence.

PMID- 23551638
TI  - Modification of xenogenic bone substitute materials--effects on the early healing
      cascade in vitro.
AB  - INTRODUCTION: Initial platelet activation with subsequent cytokine release at the
      defect site plays a crucial role in tissue integration. The aim of this study was
      to evaluate the influence of topographic and biomimetic collagen modifications of
      a xenogenic bone substitute material (BSM) on in vitro platelet activation and
      cytokine release. MATERIAL AND METHODS: Three types of xenogenic BSM were used.
      Two BSM with different levels of granularity (large granule BSM [XBSM/L], small
      granule BSM [XBSM/S]) and a BSM with collagen (XBSM/C). All three samples were
      incubated with platelet concentrate of four healthy volunteers at room
      temperature for 15 min. For all groups, highly thrombogenic collagen type 1
      served as a reference and an additional preparation with platelet concentrate
      only (without XBSM) served as control. Platelet count and cytokine release of
      VEGF, PDGF, TGF-beta, and IGF into the supernatant were measured. RESULTS:
      Compared with the control group, XBSM/C showed an increase in platelets
      consumption (mean 41,000 +/- 26,000/ml vs. 471,000 +/- 38,000/ml), cytokine
      release of VEGF (mean 46.8 +/- 7.2 pg/ml vs. 18.8 +/- 2.7 pg/ml), and PDGF (mean
      18,350 +/- 795 pg/ml vs. 2726 +/- 410 pg/ml) but not IGF (194,728 +/- 51,608
      pg/ml vs. 1,333,911 +/- 35,314 pg/ml). There was also an increase in cytokine
      release of TGF-beta in XBSM/C compared with XBSM/S (77,188 +/- 27,413 pg/ml vs.
      38,648 +/- 13,191 pg/ml), but no such difference when compared with XBSM/L
      (77,188 +/- 27,413 pg/ml vs. 53,309 +/- 29,430 pg/ml). XBSM/L showed higher
      platelets consumption (301,000 +/- 45,000 vs. 415,000 +/- 98,000) and a higher
      cytokine release of PDGF (3511 +/- 247 pg/ml vs. 3165 +/- 78 pg/ml) compared with
      XBSM/S. There was no distinct difference in the levels of VEGF, TGF-beta, and IGF
      between XBSM/L and XBSM/S. CONCLUSIONS: Topographic as well as biomimetic
      modifications of the xenogenic BSM showed an increased platelet activation and
      cytokine release in vitro. This effect on the intrinsic healing cascade could
      result in comparable enhanced soft- and hard-tissue regeneration in vivo.

PMID- 23551639
TI  - Oral mucosal status and salivary IgA levels of HIV-infected children.
AB  - BACKGROUND: Pediatric HIV is a major world health problem, which is progressing
      at an alarming rate. Lesions in the mouth and in other tissues and organs (oral
      and systemic lesions) in pediatric HIV infection are diverse and show differences
      in clinical presentation and severity from that of adults. Very little data exist
      for oral lesions in pediatric population in India. To assess oral mucosal status
      of HIV-infected children and to correlate it with their salivary IgA levels.
      METHODS: The study group consisted of 150 HIV-infected children aged 6-18 years.
      They were divided into two groups. Group 1: Children prior to anti-retroviral
      therapy, Group 2: Children undergoing anti-retroviral therapy (for not more than
      3 years). Criteria given by Ramos-Gomez for diagnosis of oral lesions commonly
      associated with HIV infection in children were used to record the oral lesions.
      Salivary IgA levels were determined by enzyme-linked immunosorbent assay. Data
      obtained were subjected to statistical analysis. RESULTS: There was a significant
      difference in mean secretory IgA (SIgA) levels between the groups (P <= 0.05).
      All the children had one or more oral mucosal lesions, with angular cheilitis
      being the most common lesion. There was a significant inverse relation between
      SIgA levels and individual oral mucosal lesions (P <= 0.05). The number of oral
      lesions was inversely related to the SIgA levels. CONCLUSION: Oral mucosal
      lesions were a significant feature of HIV-infected infection, particularly in
      children prior to the onset of anti-retroviral therapy. All children showed low
      SIgA levels. Early recognition and management of oral conditions are important to
      improve the quality of life in these children.

PMID- 23551640
TI  - Clinical characteristics and management of periesophageal vagal nerve injury
      complicating left atrial ablation of atrial fibrillation: lessons from eleven
      cases.
AB  - INTRODUCTION: This study aimed to elucidate the clinical characteristics and
      management of periesophageal vagal nerve injury complicating the ablation of
      atrial fibrillation (AF). METHODS AND RESULTS: A total of 3,695 patients with
      drug-resistant AF underwent extensive pulmonary vein isolation at our
      institution. Either a nonirrigated or an irrigated ablation catheter was
      employed, with radiofrequency power of 25-40 W. Esophageal temperature was
      monitored in 3,538 patients: when the esophageal temperature reached 42 degrees C
      radiofrequency delivery was stopped. A total of 11 patients (60 +/- 11 years, 10
      males) were diagnosed as having a periesophageal vagal nerve injury after the AF
      ablation. Symptoms included nausea, vomiting, bloating, constipation, and gastric
      pain, which occurred within 72 hours after the procedure. Gastrointestinal
      fluoroscopy and/or endoscopy revealed gastric hypomotility (10 patients) and
      pyloric spasm (1 patient). Intravenous erythromycin (3 mg/kg every 8 hours) was
      effective in relieving symptoms in 5 patients, and the patient with pyloric spasm
      underwent esophagojejunal anstomosis. Eight patients almost fully recovered
      within 40 days; however, 3 patients suffered from severe symptoms for 3-12
      months. This complication occurred in 4 of the 157 patients (2.5%) who did not
      have esophageal temperature monitoring, and 7 of the 3,538 (0.2%) who did (P =
      0.0007). The 3 patients with persistent severe symptoms received no esophageal
      temperature monitoring. CONCLUSION: The clinical course and severity of the
      periesophageal vagal nerve injury varied, but most patients finally recovered
      with conservative treatment. Radiofrequency delivery under esophageal temperature
      monitoring might reduce both the incidence and the severity of this complication.

PMID- 23551641
TI  - Measuring patient participation in surgical treatment decision-making from
      healthcare professionals' perspective.
AB  - AIMS AND OBJECTIVES: To develop, empirical test, and validate an instrument
      measuring patient participation in surgical treatment decision-making from
      healthcare professionals' perspective. BACKGROUND: Since the advent of New Public
      Management in many Western countries, patient participation in healthcare
      decision-making has been considered to be a best practice. A common notion is
      that well-educated and well-informed public want to choose their own treatments
      and providers and want to ask questions about the quality of their health
      services. DESIGN: Survey. METHODS: A self-report-measuring instrument was
      designed and administered to 620 healthcare professionals. Items were developed,
      validated and tested by 451 nurses and physicians working in six surgical wards
      in a University Hospital in Norway. RESULTS: A 16-item scale with the following
      four dimensions was developed: information dissemination, formulation of options,
      integration of information and control. Factor analysis procedures and
      reliability testing were performed. A one-way, between-groups analysis of
      variance was conducted to compare doctors' and nurses' opinions on four
      dimensions of patient participation in surgical treatment decision-making.
      CONCLUSIONS: This article shows that patient participation in surgical treatment
      decision-making can be measured by a 16-item scale and four distinct dimensions.
      The analysis demonstrated a reasonable level of construct validity and
      reliability. Nurses and physicians have a positive attitude towards patient
      participation overall, but the two groups differ in the extent to which they
      accept the idea of patient participation in treatment decision-making. RELEVANCE
      TO CLINICAL PRACTICE: The instrument can be a tool for managers and healthcare
      professionals in the implementation of patient participation in clinical
      practice. Data from the instrument can be useful to identify health services
      being provided and what areas that could strengthen patient participation.

PMID- 23551642
TI  - Rural-urban differences in consumer governance at community health centers.
AB  - CONTEXT: Community health centers (CHCs) are primary care clinics that serve
      mostly low-income patients in rural and urban areas. They are required to be
      governed by a consumer majority. What little is known about the structure and
      function of these boards in practice suggests that CHC boards in rural areas may
      look and act differently from CHC boards in urban areas. PURPOSE: To identify
      differences in the structure and function of consumer governance at CHCs in rural
      and urban areas. METHODS: Semistructured telephone interviews were conducted with
      30 CHC board members from 14 different states. Questions focused on board
      members' perceptions of board composition and the role of consumers on the board.
      FINDINGS: CHCs in rural areas are more likely to have representative boards, are
      better able to convey confidence in the organization, and are better able to
      assess community needs than CHCs in urban areas. However, CHCs in rural areas
      often have problems achieving objective decision-making, and they may have fewer
      means for objectively evaluating quality of care due to the lack of patient board
      member anonymity. CONCLUSIONS: Consumer governance is implemented differently in
      rural and urban communities, and the advantages and disadvantages in each setting
      are unique.

PMID- 23551643
TI  - Trauma patients over-triaged to helicopter transport in an established Midwestern
      state trauma system.
AB  - PURPOSE: To characterize helicopter transport use in a mature Midwestern trauma
      system located in a low population density state, examine characteristics of
      patients over-triaged to helicopter transport, and determine predictors of over
      triage to helicopter transport. METHODS: A retrospective observational study
      conducted using State Trauma Registry data for years 2008-2009. Study sample
      included patients with medical helicopter transportation. Bivariate analyses
      compared patients defined and not defined as over-triaged to helicopter
      transport. Multivariate regression was used to determine predictors of over
      triage. FINDINGS: Of the 2,084 helicopter-transported study patients, 552 (26%)
      were defined as over-triaged. Differences in patients based on over-triaged
      status included race, age, injury mechanism, injury type, and injury intent (P <
      .05). Multivariate-based significant predictors of over-triage were transfer
      status, patient age, and injury mechanism (P= .0223; <.0001; and .0007,
      respectively). Patients transported from scene had a greater odds (OR: 1.29; 95%
      confidence interval: 1.04, 1.60) of being over-triaged to helicopter transport
      than interfacility transfers. Younger patients were also more likely to be over
      triaged. Interactions between patient age and injury mechanism demonstrated
      varied likelihoods for over-triage. Younger patients injured in falls were more
      likely over-triaged than younger patients injured in a motor vehicle crash or by
      other non-fall causes. CONCLUSION: Study data showed over-triage to helicopter
      transport was substantial in a mature trauma system. It is recommended that
      trauma systems develop and monitor compliance with criteria for appropriate use
      of air medical transport. These actions can assist in refinements to prehospital
      and interfacility transfer protocols.

PMID- 23551644
TI  - The financial performance of rural hospitals and implications for elimination of
      the Critical Access Hospital program.
AB  - PURPOSE: To compare the financial performance of rural hospitals with Medicare
      payment provisions to those paid under prospective payment and to estimate the
      financial consequences of elimination of the Critical Access Hospital (CAH)
      program. METHODS: Financial data for 2004-2010 were collected from the Healthcare
      Cost Reporting Information System (HCRIS) for rural hospitals. HCRIS data were
      used to calculate measures of the profitability, liquidity, capital structure,
      and financial strength of rural hospitals. Linear mixed models accounted for the
      method of Medicare reimbursement, time trends, hospital, and market
      characteristics. Simulations were used to estimate profitability of CAHs if they
      reverted to prospective payment. FINDINGS: CAHs generally had lower unadjusted
      financial performance than other types of rural hospitals, but after adjustment
      for hospital characteristics, CAHs had generally higher financial performance.
      CONCLUSIONS: Special payment provisions by Medicare to rural hospitals are
      important determinants of financial performance. In particular, the financial
      condition of CAHs would be worse if they were paid under prospective payment.

PMID- 23551645
TI  - Measuring the performance of Critical Access Hospitals in Missouri using data
      envelopment analysis.
AB  - PURPOSE: Rural hospitals are critical for access to health care, and for their
      contributions to local economies. However, many rural hospitals, especially
      critical access hospitals (CAHs) need to strive for more efficiency for continued
      viability. Routinely evaluating their performance, and providing feedback to
      management and policy makers, is therefore important. METHOD: Three measures of
      relative efficiency are estimated for CAHs in Missouri using an Input-oriented
      Data Envelopment Analysis with a variable returns to scale assumption and
      compared with the efficiency of other rural hospitals in Missouri using Banker's
      F-test. Using 30-day readmission rate as a measure of quality, CAHs are evaluated
      against efficiency-quality dimensions. FINDINGS: CAHs in Missouri had a slight
      decline in average technical efficiency, but they had a slight gain in average
      cost efficiency in 2009 compared to 2006. More than half of the CAHs were neither
      economically nor technically efficient in both years. The relative efficiency of
      other rural hospitals was statistically higher than that of CAHs in Missouri.
      CONCLUSIONS: This study validates the finding of relative inefficiency of CAHs
      compared to other hospitals paid under the Prospective Payment System at a state
      level (Missouri). However, with considerable variation in socioeconomic as well
      as health care access indicators across states, a relative efficiency frontier
      may not be the only relevant indicator of value for the evaluation of the
      performance of CAHs. Access to health care and the impact on the local economy
      provided by these CAHs to the community are also critical indicators for more
      comprehensive performance evaluation.

PMID- 23551646
TI  - Rural relevant quality measures for critical access hospitals.
AB  - PURPOSE: To identify current and future relevant quality measures for Critical
      Access Hospitals (CAHs). METHODS: Three criteria (patient volume, internal
      usefulness for quality improvement, and external usefulness for public reporting
      and payment reform) were used to analyze quality measures for their relevance for
      CAHs. A 6-member panel with expertise in rural hospital quality measurement and
      improvement provided input regarding the final measure selection. FINDINGS: The
      relevant quality measures for CAHs include measures that are ready for reporting
      now and measures that need specifications to be finalized and/or a data reporting
      mechanism to be established. They include inpatient measures for specific medical
      conditions, global measures that address appropriate care across multiple medical
      conditions, and Emergency Department measures. CONCLUSIONS: All CAHs should
      publicly report on relevant quality measures. Acceptance of a single consolidated
      set of quality measures with common specifications for CAHs by all entities
      involved in regulation, accreditation, and payment; a phased process to implement
      the relevant measures; and the provision of technical assistance would help CAHs
      meet the challenge of reporting.

PMID- 23551648
TI  - Are primary care practices ready to become patient-centered medical homes?
AB  - PURPOSE: To measure the readiness of rural primary care practices to qualify as
      patient-centered medical homes (PCMHs), one step toward participating in changes
      underway in health care finance and delivery. METHODS: We used the 2008 Health
      Tracking Physician Survey to compare PCMH readiness scores among metropolitan and
      nonmetropolitan primary care practices. The National Committee on Quality
      Assurance (NCQA) assessment system served as a framework to assess the PCMH
      capabilities of primary care practices based on their services, processes, and
      policies. FINDINGS: We found little difference between urban and rural practices.
      Approximately 41% of all primary care practices offer minimal or no PCMH
      services. We also found that large practices score higher on standards primarily
      related to information technology and care management. CONCLUSIONS: Achieving the
      benefits of the PCMH model in small rural practices may require additional
      national promotion, technical assistance, and financial incentives.

PMID- 23551649
TI  - The metabolic syndrome: are rural residents at increased risk?
AB  - PURPOSE: The purpose of this study was to estimate the differences in prevalence
      of metabolic syndrome and its individual components across rural-urban
      populations, as well as to determine the risk factors associated with metabolic
      syndrome and examine how they contribute toward rural-urban disparity. METHODS:
      Data came from the 1999-2006 National Health and Nutrition Examination Survey,
      restricting to 6,896 participants aged 20 years or more with complete
      information. Metabolic syndrome was defined using the National Cholesterol
      Education Program's Adult Treatment Panel III criteria. Residence was measured at
      the census tract level using the Rural-Urban Commuting Area Codes. We estimated
      the prevalence of metabolic syndrome and its components by residence. Multiple
      logistic regression models were used to examine urban-rural differences after
      adjusting for sociodemographic, health, dietary, and lifestyle factors. RESULTS:
      The prevalence of metabolic syndrome was higher in rural than urban residents
      (39.9% vs 32.8%), among both men (39.7% vs 33.3%) and women (40.2% vs 32.3%,
      respectively). The age and sex adjusted OR for metabolic syndrome in rural as
      compared to urban residents was 1.23 (95% CI, 1.02-1.49), which was attenuated to
      1.06 (95% CI, 0.90-1.25) after adjusting for covariates. Older age, lower
      physical activity, higher screen time, higher meat intake, and skipping breakfast
      were associated with increased odds of metabolic syndrome. CONCLUSION: Rural
      dwelling was associated with higher prevalence of metabolic syndrome among adults
      in the Unites States, which can be attributed to the differences in demographic
      composition and obesity-related behavioral factors between urban and rural
      residents.

PMID- 23551647
TI  - Regional differences in prescribing quality among elder veterans and the impact
      of rural residence.
AB  - PURPOSE: Medication safety is a critical concern for older adults. Regional
      variation in potentially inappropriate prescribing practices may reflect
      important differences in health care quality. Therefore, the objectives of this
      study were to characterize prescribing quality variation among older adults
      across geographic region, and to compare prescribing quality across rural versus
      urban residence. METHODS: Cross-sectional study of 1,549,824 older adult veterans
      with regular Veterans Affairs (VA) primary care and medication use during fiscal
      year 2007. Prescribing quality was measured by 4 indicators of potentially
      inappropriate prescribing: Zhan criteria drugs to avoid, Fick criteria drugs to
      avoid, therapeutic duplication, and drug-drug interactions. Frequency differences
      across region and rural-urban residence were compared using adjusted odds-ratios.
      FINDINGS: Significant regional variation was observed for all indicators. Zhan
      criteria frequencies ranged from 13.2% in the Northeast to 21.2% in the South.
      Nationally, rural veterans had a significantly increased risk for inappropriate
      prescribing according to all quality indicators. However, regional analyses
      revealed this effect was limited to the South and Northeast, whereas rural
      residence was neutral in the Midwest and protective in the West. CONCLUSIONS:
      Significant regional variation in prescribing quality was observed among older
      adult veterans, mirroring recent findings among Medicare beneficiaries. The
      association between rurality and prescribing quality is heterogeneous, and
      relying solely on national estimates may yield misleading conclusions. Although
      we documented important variations in prescribing quality, the underlying factors
      driving these trends remain unknown, and they are a vital area for future
      research affecting older adults in both VA and non-VA health systems.

PMID- 23551650
TI  - Health care utilization patterns for young children in rural counties of the I-95
      corridor of South Carolina.
AB  - OBJECTIVE: The objective of this study was to assess health care utilization
      patterns for young children with Medicaid insurance in the rural counties of the
      I-95 corridor in South Carolina relative to other regions of the state. We
      hypothesize that young children received less well care and higher levels of
      tertiary care in the rural counties along the I-95 corridor (I-95) of South
      Carolina. DESIGN/METHODS: A Medicaid cohort of children less than 3 years of age
      was used to compare Early, Periodic, Diagnosis, Screening and Treatment (EPSDT)
      visits; preventable emergency department (ED) visits; and inpatient visits
      between I-95, other rural and urban county groupings. RESULTS: The adjusted odds
      of a child having had 80% of the recommended EPSDT visits were reduced for I-95
      compared to other rural counties. The odds of a preventable inpatient or ED visit
      were increased for all rural counties, with the highest rates in the other rural
      counties. CONCLUSIONS: Children accessed well care less in the I-95 corridor
      compared to other rural areas of South Carolina. Rural children accessed tertiary
      care more often than urban children, a finding most prominent outside the I-95
      corridor, likely attributable to more available access of tertiary care in rural
      counties outside the I-95 corridor.

PMID- 23551651
TI  - The influence of rural versus urban residence on utilization and receipt of care
      for chronic low back pain.
AB  - PURPOSE: (1) To describe demographic and health-related characteristics among
      rural/urban residents with chronic low back pain (LBP); (2) To determine if the
      utilization of diagnostics and treatments differs between rural and urban
      residents with chronic LBP; and (3) To determine the association between
      rural/urban residence and health care provider usage and if associations differ
      by race or gender. METHODS: A 2006 cross-sectional telephone survey of a
      representative sample of North Carolina residents. Subjects with chronic LBP were
      questioned regarding their health and health care use. Wald and chi-square tests
      were used to determine differences between demographic and health-related
      characteristics of rural/urban residents. Logistic regression was used to
      determine the association between rural/urban residence and health care provider
      use. Differences in race or gender were explored with stratified analysis with a
      P < .10. FINDINGS: 588 residents of North Carolina with self-reported chronic LBP
      sought care from a provider in the previous year. In bivariate analyses, when
      compared to urban residents, rural residents were younger, more likely to be
      uninsured, reported significantly higher levels of disability, and reported more
      depression/sadness. Rural residents were less likely to receive care from a
      rheumatologist (adjusted odds ratio [aOR] 0.47 [95% CI, 0.22-0.99]). Rural blacks
      were less likely to receive care from a physical therapist when compared to urban
      blacks (aOR 0.26 [95% CI, 0.07-0.87]). CONCLUSION: Despite similarities of high
      provider use, imaging and therapeutics, when compared to urban residents, rural
      residents reported higher levels of functional limitation and depression.

PMID- 23551652
TI  - Rural-urban differences in health services utilization in the US-Mexico border
      region.
AB  - PURPOSE: Evaluate the association between driving distance to the US-Mexico
      border and rural-urban differences in the use of health services in Mexico by US
      border residents from Texas. METHODS: Data for this study come from the Cross
      Border Utilization of Health Care Survey, a population-based telephone survey
      conducted in the Texas border region in spring 2008. Driving distances to the
      border were estimated from the nearest border crossing station using Google Maps.
      Outcome measures included medication purchases, physician visits, dentist visits,
      and inpatient care in Mexico during the 12 months prior to the survey. A series
      of adjusted logit models were estimated after controlling for relevant
      confounding factors. FINDINGS: The average driving distance to the nearest border
      crossing station among rural respondents was 4 times that of urban respondents
      (42.0 miles vs 10.3 miles [P < .001]). Rural respondents were more likely to be
      dissatisfied than urban respondents with the health care provided on the US side
      of the border, yet they were less likely to use health services in Mexico.
      Driving distance to the border largely explained the observed rural-urban
      differences in medication purchases from Mexico. In the case of inpatient care,
      however, rural respondents reported a higher utilization rate than urban
      respondents and this rural-urban difference became more pronounced after
      adjusting for the effect of driving distance to the border. CONCLUSIONS:
      Dissatisfaction with US health care services in rural communities in the US
      Mexico border region seems to be compounded by the lack of access to health care
      services in Mexico due to travel distance constraints.

PMID- 23551653
TI  - Montana primary care providers' access to and satisfaction with pediatric
      specialists when caring for children with special health care needs.
AB  - PURPOSE: Primary care providers (PCPs) of children with special health care needs
      (CSHCN) in rural areas face challenges in accessing specialty care to support a
      patient-centered medical home. This study assessed the practice characteristics
      and attitudes regarding pediatric specialty care among Montana PCPs of CSHCN.
      METHODS: We surveyed 433 Montana PCPs identified through a statewide registry.
      Demographic and practice information was collected, including the proportion of
      time spent on CSHCN care coordination. A 5-point Likert scale was used to
      calculate mean need scores for each pediatric specialty, access to these
      specialties, and barriers to care. Results were analyzed separately for
      pediatricians and family physicians, as well as rural and urban providers, using
      lambda2, t tests, and Mann-Whitney tests. RESULTS: Of the PCPs surveyed, 386 had
      a valid address and were currently practicing in Montana, 112 (29%) responded,
      and 91 provided care to CSHCN (averaged 29% of time spent in CSHCN care
      coordination). Child psychiatry (4.1) and developmental/behavioral pediatrics
      (3.7) were identified as the most needed specialties, yet they scored lowest in
      access to care (2.2 and 2.6, respectively). The most important rated specialist
      characteristics were quality (4.1), availability (3.5), and communication skills
      (2.8). Among the top barriers to care, lack of appropriate specialists was
      identified by 82% of PCPs. CONCLUSIONS: Specialty care delivery for CSHCN in
      rural areas such as Montana should focus on matching availability with the
      identified need for specialty services, and ensuring that systems of
      communication between PCPs and specialists support the care coordination function
      of PCPs.

PMID- 23551654
TI  - Whole body application of a potent topical corticosteroid for bullous pemphigoid.
AB  - BACKGROUND: Current standard of treatment of bullous pemphigoid (BP) is systemic
      oral corticosteroids (CS). However, significant iatrogenic morbidity and
      mortality is reported. Studies have shown that topical potent CS is safer than
      oral prednisolone in BP. OBJECTIVES: To examine the local and systemic efficacy
      and adverse effects of whole body clobetasol propionate cream application in
      patients with mild or severe BP. METHODS: Open, clinical records-based
      retrospective analysis of a series of mild (n = 40) and severe (n = 34) BP
      patients, treated with ranging doses (20-40 g/day) clobetasol propionate cream.
      For assessing systemic effects, we observed in selected cases eosinophil count
      and morning urine cortisol level. RESULTS: Patients with mild BP achieved in
      90.0% disease control and in severe BP in 73.5%. Complete remission was achieved
      in mild BP in 64.1% (35.9% off therapy and 28.2% on therapy) vs. 41.2% in severe
      BP (5.9% off therapy and 35.3% on therapy). Local adverse effects were mainly
      skin atrophy (14.9%) and purpura (5.4%). Systemic adverse effects were rare (n =
      3) and consisted of deep vein thrombosis, hypertrichosis and adrenocortical
      insufficiency. Systemic effect was witnessed by immediate drop of eosinophil
      count, and decrease in the morning urine cortisol in selected cases. CONCLUSIONS:
      Topical whole body application of clobetasol propionate cream as monotherapy can
      be effective and safe in the induction phase of treatment in mild BP and severe
      BP. When relapse occurs adjuvant systemic medication is mandatory. Potent CS
      works locally and systemically against BP, at the price of significant local and
      less significant systemic adverse effects.

PMID- 23551655
TI  - Applicability of automated functional imaging for assessing right ventricular
      function.
AB  - BACKGROUND: Understanding of right ventricular (RV) function has significantly
      improved in recent years; however, objective assessment remains problematic. This
      study sought to demonstrate that a novel speckle tracking method can be used to
      assess RV global systolic function when compared with traditional
      echocardiographic measures. METHODS: A total of 125 patients (mean age 50 +/- 16
      years) with a wide range not only of systolic function for both ventricles but
      also pulmonary pressures and acoustic windows based on patient's body surface
      areas were studied. Standard parameters of left and RV systolic function were
      collected and echocardiographic images from four-chamber apical planes were
      analyzed by conventional manual tracing using a novel General Electric (GE)
      automated functional imaging (AFI) to measure myocardial strain. RESULTS: Global
      longitudinal RV strain measurements obtained with manual tracing showed good
      correlation with traditional parameters of main RV chamber as well as right
      ventricular outflow tract (RVOT) systolic performance. In a stepwise multiple
      regression analysis, tricuspid annular systolic motion was the best independent
      variable that correlated with global AFI RV peak systolic strain followed by RV
      outflow tract systolic excursion. Receiver operating characteristic analysis
      showed a global RV AFI peak systolic strain value <-17% to be abnormal
      (sensitivity 73%, specificity 91%). DISCUSSION: This new automated AFI method
      provides simultaneous quantitation of global and regional RV function that is
      angle independent and correlates with standard measures of RV performance without
      the need for additional derivative measurements, complex calculations, or tedious
      offline analysis.

PMID- 23551656
TI  - Fine needle aspiration cytology of nodular thyroid lesions: a 2-year experience
      of the Bethesda system for reporting thyroid cytopathology in a large regional
      and a university hospital, with histological correlation.
AB  - OBJECTIVE: Thyroid fine needle aspiration (FNA) contributes to the appropriate
      management of nodular thyroid lesions. The introduced categories in the Bethesda
      system for reporting thyroid cytopathology (TBSRTC) are associated with an
      implied cancer risk, providing a clinical management guideline. This study aims
      to evaluate the reproducibility of this implied risk and to compare the results
      from two different cytopathology departments. METHODS: Five hundred
      histologically confirmed FNAs, studied since the introduction of TBSRTC, were
      obtained from 4208 and 3587 FNAs performed in a large regional hospital in
      Herakleion, Crete (group A) and a university hospital in Athens (group B),
      respectively. Reports were issued according to TBSRTC. Aspirates were prepared
      with ThinPrep((r)) and evaluated by two experienced cytopathologists. The
      reproducibility and accuracy were evaluated. RESULTS: The proportion test for
      suspicious for malignancy (SFM) and malignant (M) cytology reports (P < 0.0001),
      and the number of malignancies on histology (P < 0.0001), were significantly
      higher in group A than in group B, consistent with a higher incidence of thyroid
      carcinomas in southern Greece. Although the malignancy rates were higher in group
      A than in group B for all categories, except M (A, 99.3%; B, 100%), the
      difference was only significant for benign aspirates (P = 0.0303). Malignancy
      rates for all categories in group A were above the TBSRTC recommended range, but
      were consistent with an increased prevalence of malignancy in that centre,
      differences in reporting practice and the variable ranges reported in the
      literature. There was lower sensitivity (P = 0.019) and overall accuracy (P =
      0.003) in group A relative to group B, but no difference in specificity.
      CONCLUSIONS: TBSRTC provides valuable information for the appropriate management
      of nodular thyroid lesions, both in a university and a large regional hospital.

PMID- 23551657
TI  - Effects of celecoxib on hematoma and edema volumes in primary intracerebral
      hemorrhage: a multicenter randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective
      inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH).
      METHODS: We conducted a multicenter, randomized, controlled, and open with
      blinded end-point trial of 44 Korean patients 18 years or older with ICH within
      24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a
      day) for 14 days. The control group (n = 24) received the standard medical
      treatment for ICH. The primary end-point was the number of patients with a change
      in the volume of perihematomal edema (PHE) from the 1st to the 7th +/- 1 day (cut
      off value, 20%). RESULTS: The time from onset to computed tomography scan
      slightly differed between groups (177 +/- 160 min for control vs. 297 +/- 305 min
      for the celecoxib group; P = 0.10). In the primary end-point analysis using cut
      off values, there was a significant shift to reduced expansion of PHE in the
      celecoxib group (P = 0.005). With respect to the secondary end-points, there was
      also a significant shift to reduced expansion of ICH in the celecoxib group (P =
      0.046). In addition, the expansion rate of PHE at follow-up tended to be higher
      in the control group than in the celecoxib group (90.6 +/- 91.7% vs. 44.4 +/-
      64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of
      celecoxib in the acute stage of ICH was associated with a smaller expansion of
      PHE than that observed in controls.

PMID- 23551658
TI  - Production and evaluation of the utility of novel phage display-derived peptide
      ligands to Salmonella spp. for magnetic separation.
AB  - AIMS: The objectives of this study were to produce Salmonella-specific peptide
      ligands by phage display biopanning and evaluate their use for magnetic
      separation (MS). METHODS AND RESULTS: Four-phage display biopanning rounds were
      performed, and the peptides expressed by the two most Salmonella-specific (on the
      basis of phage-binding ELISA results) phage clones, MSal020401 and MSal020417,
      were chemically synthesized and coupled to MyOneTM tosylactivated Dynabeads((r)).
      Peptide capture capability for whole Salmonella cells from nonenriched broth
      cultures was quantified by MS + plate counts and MS + GreenlightTM detection and
      compared to capture capability of anti-Salmonella (antibody-coated)
      Dynabeads((r)). MS + GreenlightTM gave a more comprehensive picture of capture
      capability than MS + plate counts and showed that Peptide MSal020417-coated beads
      exhibited at least similar, if not better, capture capability to anti-Salmonella
      Dynabeads((r)) (mean capture values of 36.0 +/- 18.2 and 31.2 +/- 20.1%,
      respectively, over Salmonella spp. concentration range 3 * 10(1) -3 * 10(6) CFU
      ml(-1)) with cross-reactivity of <=1.9% to three other foodborne pathogens:
      Escherichia coli, Listeria monocytogenes and Campylobacter jejuni. CONCLUSIONS:
      One of the phage display-derived peptide ligands was demonstrated by MS +
      GreenlightTM to be a viable antibody alternative for MS of Salmonella spp.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates an antibody-free
      approach to Salmonella detection and opens substantial possibilities for more
      rapid tests for this bacterium.

PMID- 23551659
TI  - Engineering sleep to discover the function of slow wave activity (Commentary on
      Antonenko et al.).

PMID- 23551660
TI  - Brain region-specific transcriptomic markers of serotonin-1A receptor agonist
      action mediating sexual rejection and aggression in female marmoset monkeys.
AB  - INTRODUCTION: In a marmoset model of hypoactive female sexual function, we have
      shown that repeated administration of the serotonin (5-HT)-1A agonist R-(+)-8
      hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) inhibits sexual receptivity in
      female marmoset monkeys and increases aggression toward the male pairmate. AIM:
      The aims of this study are to investigate gene expression changes induced by 8-OH
      DPAT in laser-microdissected brain areas that regulate female sexual function and
      to identify genes, functional gene classes, and pathways associated with 8-OH
      DPAT-mediated inhibition of female sexual receptivity. METHODS: Gene expression
      was measured in the medial prefrontal cortex (mPFC), medial preoptic area (mPOA),
      cornu ammonis-1 (CA1) area of the hippocampus (CA1), and dorsal raphe nucleus
      (DRN) of four 8-OH-DPAT-treated (0.1 mg/kg; daily administration for 16 weeks)
      and four vehicle-treated female marmosets using a marmoset-specific microarray
      (European Marmoset Microarray [EUMAMA]) and validated by real-time quantitative
      polymerase chain reaction (RTqPCR). Enriched functional gene classes were
      determined. In a parallel candidate gene approach, the expression of serotonergic
      candidate genes, i.e., the 5-HT1A, 5-HT2A, and 5-HT7 receptors and the 5-HT
      transporter (5-HTT), was measured by RTqPCR. MAIN OUTCOME MEASURES: The main
      outcome is the differential expression of genes between 8-OH-DPAT- and vehicle
      treated marmosets. RESULTS: 8-OH-DPAT affected the gene classes important to
      neural development (mPFC, mPOA, and DRN), neurotransmission (mPOA), energy
      production (mPFC and mPOA), learning and memory (CA1), and intracellular signal
      transduction (DRN). Oxytocin (OXT) in the mPOA and 5-HTT in the DRN were strongly
      increased by 8-OH-DPAT. 5-HT1A tended to increase in the mPFC, while 5-HT7 was
      decreased in the CA1. CONCLUSIONS: Brain region-specific alterations of gene
      expression regulating neural circuitries, energy demands, and learning processes
      are associated with 8-OH-DPAT-induced decrease in female sexual receptivity and
      increase in pairmate aggression. The role of OXT in the serotonergic regulation
      of female sexual behavior and partner interactions warrants attention in future
      studies.

PMID- 23551661
TI  - Doppler sonographic evaluation of arteriovenous shunt flow in a fetus with dural
      sinus malformation.
AB  - Dural sinus malformation (DSM) is a rare congenital malformation characterized by
      a dilated dural sinus pouch. We present a case of prenatally diagnosed DSM and
      propose a parameter to predict poor fetal outcome. Detailed ultrasonography at 26
      weeks of our patient showed an intracranial cyst in the left posterior fossa.
      Color Doppler study indicated an arteriovenous shunt within the cyst with
      increased blood flow velocity. Based on these findings, fetal DSM with
      arteriovenous shunt was diagnosed. Because of fetal hydrops with high-output
      cardiac failure and maternal pregnancy-induced hypertension, labor was induced at
      32 weeks and resulted in stillbirth. In conclusion, based on the present case, we
      can deduce that color Doppler study is useful for prenatal diagnosis of DSM with
      arteriovenous shunt and that a high-flow velocity to the cystic lesion is a
      possible predictor of hydropic change in such fetuses.

PMID- 23551662
TI  - Low-level light therapy for androgenetic alopecia: a 24-week, randomized, double
      blind, sham device-controlled multicenter trial.
AB  - BACKGROUND: Androgenetic alopecia (AGA) is a common disorder affecting men and
      women. Finasteride and minoxidil are well-known, effective treatment methods, but
      patients who exhibit a poor response to these methods have no additional adequate
      treatment modalities. OBJECTIVE: To evaluate the efficacy and safety of a low
      level light therapy (LLLT) device for the treatment of AGA. METHODS: This study
      was designed as a 24-week, randomized, double-blind, sham device-controlled
      trial. Forty subjects with AGA were enrolled and scheduled to receive treatment
      with a helmet-type, home-use LLLT device emitting wavelengths of 630, 650, and
      660 nm or a sham device for 18 minutes daily. Investigator and subject performed
      phototrichogram assessment (hair density and thickness) and global assessment of
      hair regrowth for evaluation. RESULTS: After 24 weeks of treatment, the LLLT
      group showed significantly greater hair density than the sham device group. Mean
      hair diameter improved statistically significantly more in the LLLT group than in
      the sham device group. Investigator global assessment showed a significant
      difference between the two groups, but that of the subject did not. No serious
      adverse reactions were detected. CONCLUSION: LLLT could be an effective treatment
      for AGA.

PMID- 23551663
TI  - The hybrid four-CBS-domain KINbetagamma subunit functions as the canonical gamma
      subunit of the plant energy sensor SnRK1.
AB  - The AMPK/SNF1/SnRK1 protein kinases are a family of ancient and highly conserved
      eukaryotic energy sensors that function as heterotrimeric complexes. These
      typically comprise catalytic alpha subunits and regulatory beta and gamma
      subunits, the latter function as the energy-sensing modules of animal AMPK
      through adenosine nucleotide binding. The ability to monitor accurately and adapt
      to changing environmental conditions and energy supply is essential for optimal
      plant growth and survival, but mechanistic insight in the plant SnRK1 function is
      still limited. In addition to a family of gamma-like proteins, plants also encode
      a hybrid betagamma protein that combines the Four-Cystathionine beta-synthase
      (CBS)-domain (FCD) structure in gamma subunits with a glycogen-binding domain
      (GBD), typically found in beta subunits. We used integrated functional analyses
      by ectopic SnRK1 complex reconstitution, yeast mutant complementation, in-depth
      phylogenetic reconstruction, and a seedling starvation assay to show that only
      the hybrid KINbetagamma protein that recruited the GBD around the emergence of
      the green chloroplast-containing plants, acts as the canonical gamma subunit
      required for heterotrimeric complex formation. Mutagenesis and truncation
      analysis further show that complex interaction in plant cells and gamma subunit
      function in yeast depend on both a highly conserved FCD and a pre-CBS domain, but
      not the GBD. In addition to novel insight into canonical AMPK/SNF/SnRK1 gamma
      subunit function, regulation and evolution, we provide a new classification of
      plant FCD genes as a convenient and reliable tool to predict regulatory partners
      for the SnRK1 energy sensor and novel FCD gene functions.

PMID- 23551664
TI  - Finite element analysis of an implant-assisted removable partial denture.
AB  - PURPOSE: This study analyzes the effects of loading a Kennedy class I implant
      assisted removable partial denture (IARPD) using finite element analysis (FEA).
      Standard RPDs are not originally designed to accommodate a posterior implant load
      point. The null hypothesis is that the introduction of posteriorly placed
      implants into an RPD has no effect on the load distribution. MATERIALS AND
      METHODS: A Faro Arm scan was used to extract the geometrical data of a human
      partially edentulous mandible. A standard plus regular neck (4.8 * 12 mm)
      Straumann(r) implant and titanium matrix, tooth roots, and periodontal ligaments
      were modeled using a combination of reverse engineering in Rapidform XOR2 and
      solid modeling in Solidworks 2008 FEA program. The model incorporated an RPD and
      was loaded with a bilateral force of 120 N. ANSYS Workbench 11.0 was used to
      analyze deformation in the IARPD and elastic strain in the metal framework.
      RESULTS: FEA identified that the metal framework developed high strain patterns
      on the major and minor connectors, and the acrylic was subjected to deformation,
      which could lead to acrylic fractures. The ideal position of the neutral axis was
      calculated to be 0.75 mm above the ridge. CONCLUSION: A potentially destructive
      mismatch of strain distribution was identified between the acrylic and metal
      framework, which could be a factor in the failure of the acrylic. The metal
      framework showed high strain patterns on the major and minor connectors around
      the teeth, while the implant components transferred the load directly to the
      acrylic.

PMID- 23551666
TI  - Treatment of severe genetic dyslipidemia: where are we going?

PMID- 23551667
TI  - Updates in apheresis and atherosclerotic research.

PMID- 23551668
TI  - Current ways of treating dyslipidemias to prevent atherosclerosis.

PMID- 23551669
TI  - Severe hypertriglyceridemia-related acute pancreatitis.
AB  - Acute pancreatitis is a potentially life-threatening complication of severe
      hypertriglyceridemia. In some cases, inborn errors of metabolism such as
      lipoprotein lipase deficiency, apoprotein C-II deficiency, and familial
      hypertriglyceridemia have been reported as causes of severe hypertriglyceridemia.
      More often, severe hypertriglyceridemia describes various clinical conditions
      characterized by high plasma levels of triglycerides (>1000 mg/dL), chylomicron
      remnants, or intermediate density lipoprotein like particles, and/or
      chylomicrons. International guidelines on the management of acute pancreatitis
      are currently available. Standard therapeutic measures are based on the use of
      lipid-lowering agents (fenofibrate, gemfibrozil, niacin, Omega-3 fatty acids),
      low molecular weight heparin, and insulin in diabetic patients. However, when
      standard medical therapies have failed, non-pharmacological approaches based upon
      the removal of triglycerides with therapeutic plasma exchange can also provide
      benefit to patients with severe hypertriglyceridemia and acute pancreatitis.
      Plasma exchange could be very helpful in reducing triglycerides levels during the
      acute phase of hyperlipidemic pancreatitis, and in the prevention of recurrence.
      The current evidence on management of acute pancreatitis and severe
      hypertriglyceridemia, focusing on symptoms, treatment and potential complications
      is reviewed herein.

PMID- 23551670
TI  - Multi-modal imaging technologies in cardiovascular risk assessment.
AB  - Atherosclerotic plaques can be responsible for life-threatening cardiovascular
      and cerebrovascular events. Some features of the plaque, such as a thin fibrous
      cap, large necrotic core, macrophage infiltration, neovascularization, and
      intraplaque hemorrhage, are associated with a major risk of such events and so
      their assessment is fundamental. Novel imaging techniques, each one with its own
      strength and drawbacks, can help in the evaluation and quantification of
      atherosclerosis. An analysis of the recent literature was carried out. The
      different techniques were compared by evaluating the accuracy of each one in the
      detection and assessment of the atherosclerotic plaque's features named above.

PMID- 23551671
TI  - Management of inherited atherogenic dyslipidemias in children.
AB  - In order to prevent cardiovascular disease, the treatment of inherited
      dyslipidemias in childhood represents an emerging topic capturing scientists'
      consideration. A body of findings emerged in the last decade for diagnosis and
      therapy, and results were recently summarized to introduce new guidelines by the
      American Academy of Pediatrics and National Institute for Health and Clinical
      Excellence. It is well known and generally shared the need to detect affected
      children precociously, when the family history address to genetic dyslipidemia
      and when familial premature cardiovascular disease occurs. A spectrum of
      disorders involving lipoproteins could be recognized by specific biochemical and
      genetic markers. A defined diagnosis represents the starting point to establish a
      correct treatment and follow-up program. This review represents a literature
      synthesis of the main cornerstones and criticisms concerning the screening
      program and management of atherogenic inherited dyslipidemias in children and
      adolescents.

PMID- 23551672
TI  - Prevention and treatment of cardiovascular disease in women: the obstetric
      gynecologist's point of view.
AB  - It has been confirmed that cardiovascular disease (CVD) is the leading cause of
      morbidity and mortality not only in men but also in women. The most recent
      American Heart Association (AHA) and European Atherosclerosis Society (EAS)
      recommendations specifically address women. This is in response to the majority
      of studies that primarily involved men. Ideal cardiovascular health has been
      defined for women, and new factors were added to the traditional risk factors. As
      stated by the American and European Menopause Societies (NAMS and EMAS), hormone
      replacement therapy (HRT) is no longer believed to be protective for CVD; on the
      contrary, women benefit just as much as men from statins to lower their risk of
      heart disease. At the onset of menopause, women exhibit an increase in
      cholesterol and an increased risk of CVD. Unfortunately, hyperlipidemia is
      largely undertreated in women, although the rate of hypercholesterolemia among
      women is similar to that of men. More aggressive intervention is recommended for
      persons with multiple risk factors and/or monogenic dyslipidemias. In women
      affected by familial hypercholesterolemia in the homozygous and compound forms,
      treatment such as lipoprotein apheresis is also suggested. There is evidence for
      the use of these techniques even in pregnancy. An update on the most recent
      guidelines issued by AHA, EAS, NAMS and EMAS for the prevention of CVD in women
      along with a brief overview on the use of lipoprotein apheresis in women during
      pregnancy is reported.

PMID- 23551673
TI  - Italian multicenter study on low-density lipoprotein apheresis Working Group 2009
      survey.
AB  - We present results of the second survey of the Italian Multicenter Study on Low
      Density Lipoprotein Apheresis (IMSLDLa-WG/2). The study involved 18 centers in
      2009, treating 66 males and 35 females, mean age 47 +/- 18 years. Mean age for
      initiation of drug treatment before low-density lipoprotein apheresis (LDLa) was
      31 +/- 18 years, mean age to the first LDLa was 37 +/- 20 years and average
      duration of treatment was 9 +/- 6 years. The techniques used included direct
      adsorption of lipids, dextran sulfate cellulose adsorption, heparin-mediated low
      density lipoprotein (LDL) precipitation, cascade filtration, and plasma exchange.
      The mean treated plasma/blood volumes/session were 3127 +/- 518 mL and 8666 +/-
      1384 mL, respectively. The average plasma volume substituted was 3500 +/- 300 mL.
      Lipid therapy before LDLa included ezetimibe, statins, omega-3 fatty acids and
      fenofibrate. Baseline mean LDL cholesterol (LDLC) levels were 386 +/- 223 mg/dL.
      The mean before/after apheresis LDLC level decreased by 67% from 250 +/- 108
      mg/dL (P = 0.05 vs. baseline) to 83 +/- 37 mg/dL (P = 0.001 vs. before). Baseline
      mean Lipoprotein(a) [Lp(a)] level was 179 +/- 136 mg/dL. Mean before/after
      apheresis Lp(a) level decreased by 71% from 133 +/- 120 mg/dL (P = 0.05 vs.
      baseline) to 39 +/- 44 mg/dL (P = 0.001 vs. before). Major and minor side effects
      occurred in 27 and 62 patients, respectively. Among patients with coronary artery
      disease (CAD), 62.3% had coronary angiography and 50.4% coronary
      revascularization before LDLa. Single vessel, double vessel and triple vessel CAD
      occurred in 19 (30.1%), 15 (23.8%) and 29 (46%) patients, respectively. Both CAD
      and extra-CAD occurred in 41.5%, 39% had hypertension, 9.9% were smokers, 9.9%
      consumed alcohol and 42% were physically active. Ischemic cardiovascular events
      were not observed in any patient over 9 +/- 6 years of treatment. Two centers
      have also treated 34 patients (females: 17/males 17; no. sessions: 36; average
      plasma volume treated: 3000 mL) for sudden hearing loss (SHL). Relief of symptoms
      was obtained, independently of the system used (HELP; cascade-filtration).

PMID- 23551674
TI  - Why an apheresis center should offer more than one lipoprotein apheresis method.
AB  - We describe our experience with the performance of six lipoprotein apheresis
      methods (HELP, TheraSorb LDL, DALI, lipidfiltration, Liposorber D, MONET) which
      have been used in 68 patients. Thirty-four of them have been treated with more
      than one method. The calculations presented in this paper are based on laboratory
      data measured at the last three available apheresis sessions before the switch to
      another method and at the end of the observation period, respectively. With
      respect to the reduction of low-density lipoprotein (LDL) cholesterol, DALI and
      Liposorber D appeared to be the most effective lipoprotein apheresis methods, for
      reduction of lipoprotein(a), Liposorber D. Data on the influence of these
      lipoprotein apheresis methods on parameters of the coagulation system
      (prothrombin time, international normalized ratio, activated partial
      thromboplastin time, fibrinogen) are also reported. The histories of three
      patients who have been switched to several lipoprotein apheresis methods are
      given as examples. The major reason for switching was the low efficiency of a
      given lipoprotein apheresis method with respect to lowering of LDL cholesterol;
      the reason for this phenomenon was not clear in each case. In three patients who
      took an oral anticoagulant and were treated with HELP, the influence on the
      coagulation system is reported; they were submitted to another apheresis method.
      In two patients we observed an allergy to heparin-they were then treated with a
      heparin-free apheresis method. In conclusion, we point out that there are several
      reasons why an apheresis center should offer more than one lipoprotein apheresis
      method.

PMID- 23551675
TI  - Therapeutic potential of low-density lipoprotein apheresis in the management of
      peripheral artery disease in patients with chronic kidney disease.
AB  - Cardiovascular disease (CVD) is a major cause of death in patients with chronic
      kidney disease (CKD). Patients with CKD are reported to have a significant
      greater risk of CVD-associated mortality than that of the general population
      after stratification for age, gender, race, and the presence or absence of
      diabetes. CKD itself is also an independent risk factor for the development of
      atherosclerosis, and in particular, patients undergoing dialysis typically bear
      many of the risk factors for atherosclerosis, such as hypertension, dyslipidemia
      and disturbed calcium-phosphate metabolism, and commonly suffer from severe
      atherosclerosis, including peripheral arterial disease (PAD). Low-density
      lipoprotein (LDL) apheresis is a potentially valuable treatment applied to
      conventional therapy-resistant hypercholesterolemic patients with coronary artery
      disease and PAD. Although previous and recent studies have suggested that LDL
      apheresis exerts beneficial effects on the peripheral circulation in dialysis
      patients suffering from PAD, probably through a reduction of not only serum
      lipids but also of inflammatory or coagulatory factors and oxidative stress, the
      precise molecular mechanisms underlying the long-term effects of LDL apheresis on
      the improvement of the peripheral circulation remains unclear and warrants
      further investigation.

PMID- 23551676
TI  - Novel inflammatory marker in dialysis patients: YKL-40.
AB  - YKL-40 has been introduced as a marker of inflammation in different clinical
      situations. The association between YKL-40 and inflammation in chronic renal
      failure patients has not been researched currently. The objectives of this study
      were to establish serum YKL-40 concentrations in dialysis patients with chronic
      renal failure compared to healthy subjects and to explore its relationships with
      a proinflammatory cytokine, interleukine-6 (IL-6) and an acute phase mediator,
      high sensitivity C-reactive protein (hs-CRP). The study population included
      hemodialysis patients (N = 43; mean age of 40.9 +/- 14.5), peritoneal dialysis
      patients (N = 38; mean age of 45.8 +/- 13.7) and healthy subjects (N = 37; mean
      age of 45.5 +/- 10.6). Serum concentrations of YKL-40, IL-6, hs-CRP and routine
      laboratory measures were evaluated. Compared to the healthy subjects,
      hemodialysis and peritoneal dialysis patients had higher concentrations of YKL
      40, IL-6, hs-CRP, as well as lower concentrations of hemoglobin, serum albumin
      and high density lipoprotein-cholesterol (P < 0.001). YKL-40 concentrations were
      positively correlated with serum creatinine (P < 0.001, r = 0.495), IL-6 (P <
      0.001, r = 0.306), hs-CRP (P = 0.001, r = 0.306) levels and inversely correlated
      with hemoglobin (P = 0.002, r = -0.285), serum albumin (P < 0.001, r = -0.355)
      and high density lipoprotein-cholesterol (P = 0.001, r = -0.306). In multivariate
      regression analysis YKL-40 was associated with creatinine, serum albumin and hs
      CRP concentrations after adjustments with covariates. Dialysis patients with
      chronic renal failure have elevated serum YKL-40 concentrations. Associations
      with standard inflammatory parameters suggest that YKL-40 might be a novel
      inflammatory marker in this population.

PMID- 23551677
TI  - Regional citrate anticoagulation for high volume continuous venovenous
      hemodialysis in surgical patients with high bleeding risk.
AB  - Acute kidney injury requiring renal replacement therapy occurs in up to 10% of
      all intensive care unit patients. Those who are hemodynamically unstable are
      often treated with continuous renal replacement therapy requiring continuous
      anticoagulation of the extracorporeal circuit. This is usually achieved by
      infusion of unfractionated heparin, which subsequently increases the risk of
      bleeding. To avoid systemic anticoagulation for continuous renal replacement
      therapy, regional anticoagulation with citrate has been introduced. We studied
      safety and efficacy of regional citrate anticoagulation for continuous venovenous
      hemodialysis in surgical patients requiring high dialysis doses. This was an
      observational prospective study in a 40-bed surgical intensive care unit at a
      university hospital. During a 12-month study period, all consecutive critically
      ill patients with high risk of bleeding requiring continuous renal replacement
      therapy continuous renal replacement therapy were treated with citrate
      anticoagulation for continuous venovenous hemodialysis. Prescribed dialysis dose
      was 45 mL/kg per h with a 10% increase for expected downtime. We studied filter
      lifetime, delivered dialysis dose, control of acid-base status, bleeding
      episodes, and adverse effects, that is, citrate intolerance. The total number of
      filters analyzed in 75 patients was 100. Mean (+/- standard deviation) filter
      running time was 78 +/- 25 h. Fifty-one circuits had to be renewed because of
      extended filter running time (96 +/- 18 h), 33 discontinued for reasons not
      related to renal replacement therapy (62 +/- 19 h), and 13 due to filter clotting
      (58 +/- 18 h). The mean dialysis dose during the first 72 h was 49 +/- 14 mL/kg
      per h. Overall, acid-base status after 72 h was well controlled in 62% of
      patients, metabolic alkalosis (pH > 7.45) occurred in 29%, and metabolic acidosis
      (pH < 7.35) in 9%. In one patient, treatment was stopped because of citrate
      accumulation. Citrate intoxication or overt bleeding episodes were not observed.
      Regional citrate anticoagulation for continuous venovenous hemodialysis is a safe
      and effective method to deliver a high dialysis dose in critically ill patients
      with a high risk of bleeding. Filter patency was excellent, acid-base status was
      well controlled, and clinically relevant adverse effects were not observed.
      Therefore, citrate anticoagulated continuous venovenous hemodialysis is a useful
      treatment option for patients with acute kidney injury requiring high dialysis
      doses and at risk of bleeding.

PMID- 23551678
TI  - Risk factors for recurrence of immunoglobulin a nephropathy after renal
      transplantation: single center study.
AB  - We investigated the risk factors for recurrence of IgA nephropathy after kidney
      transplantation. Of the 184 recipients of allografts for end-stage renal disease
      caused by primary IgA nephropathy at our institution and affiliated hospitals
      between 1990 and 2005, 70 developed recurrent IgA nephropathy (group 1), while
      the remaining 114 did not develop recurrent IgA nephropathy (group 2). The
      diagnosis of recurrent IgA nephropathy was based on case and/or protocol renal
      biopsies. We examined the risk factors for recurrence of IgA nephropathy by
      comparing the two groups. In addition, we also investigated the risk factors for
      graft loss in the patients with recurrent IgA nephropathy. The recipient's age at
      transplantation was significantly younger in group 1 than in group 2 (33.4 +/-
      10.4 vs. 36.7 +/- 10.7, P = 0.037). No significant influence of the
      immunosuppressive regimens used was observed on the likelihood of recurrence of
      IgA nephropathy. In the analysis of the risk factors for graft loss, the mean age
      of the donor was significantly higher in the patient group with graft loss (59.1
      +/- 9.5 vs. 53.9 +/- 9.0, P = 0.033), and the serum creatinine level at one year
      after surgery was also significantly higher in the patient group with graft loss
      (1.62 +/- 0.52 vs. 1.34 +/- 0.34, P = 0.022). Recipients with recurrent IgA
      nephropathy after transplantation, especially younger patients, need to be
      followed up carefully.

PMID- 23551679
TI  - Serum phosphate and calcium should be primarily and consistently controlled in
      prevalent hemodialysis patients.
AB  - Mineral metabolism affects mortality in hemodialysis patients and is identified
      by imbalances in serum phosphate (P), calcium (Ca), and parathyroid hormone
      (PTH). We examined associations between annual mineral values (P, Ca, PTH) and
      mortality in a 3-year cohort (Dec 2006-2009) of 128,125 hemodialysis patients
      using three models, that is, baseline, time-dependent and time-average Cox
      models. We also examined associations between achieved Japanese guideline targets
      (P: 3.5-6.0 mg/dL, corrected Ca 8.4-10.0 mg/dL, intact PTH 60-180 mg/dL) and all
      cause survival to elucidate which parameter should be controlled as a priority.
      High and low serum P (>6.0 or <= 3.5 mg/dL), high Ca (>9.5 mg/dL), higher PTH
      (>300 pg/mL) and lower PTH (<= 60 pg/mL) were significantly associated with high
      mortality in all three models (P < 0.01). When we examined the association
      between combination of mineral targets and mortality, patients who achieved all
      targets simultaneously (20% of subjects, reference) showed lowest mortality.
      Those who achieved both P and Ca targets showed the same mortality as the
      reference group. Those who only met P target had a lower risk of death (hazard
      ratio = 1.17) compared to those that achieved Ca or PTH target (1.41, 1.47,
      respectively). As time of achieving P and Ca targets increased, all-cause
      mortalities diminished incrementally, significantly. Mineral metabolism disorder
      would lead to high mortality in prevalent hemodialysis patients. Among mineral
      values, P would be the strongest predictor for high mortality. Consistent
      achievement of P and Ca targets would lead to good survival.

PMID- 23551680
TI  - 2011 JSDT standard on the management of endotoxin retentive filter for dialysis
      and related therapies.

PMID- 23551681
TI  - Differences in reduction of coagulation factor XIII (F13) between
      immunoadsorption plasmapheresis and double filtration plasmapheresis.

PMID- 23551682
TI  - Drugs affecting the renin-angiotensin system and preservation of residual renal
      function in dialysis patients.

PMID- 23551683
TI  - Effect of renin-angiotensin system inhibitor on residual glomerular filtration
      rate in hemodialysis patients.

PMID- 23551687
TI  - Assessing the influence of physical, geochemical and biological factors on
      anaerobic microbial primary productivity within hydrothermal vent chimneys.
AB  - Chemosynthetic primary production supports hydrothermal vent ecosystems, but the
      extent of that productivity and its governing factors have not been well
      constrained. To better understand anaerobic primary production within massive
      vent deposits, we conducted a series of incubations at 4, 25, 50 and 90  degrees
      C using aggregates recovered from hydrothermal vent structures. We documented in
      situ geochemistry, measured autochthonous organic carbon stable isotope ratios
      and assessed microbial community composition and functional gene abundances in
      three hydrothermal vent chimney structures from Middle Valley on the Juan de Fuca
      Ridge. Carbon fixation rates were greatest at lower temperatures and were
      comparable among chimneys. Stable isotope ratios of autochthonous organic carbon
      were consistent with the Calvin-Benson-Bassham cycle being the predominant mode
      of carbon fixation for all three chimneys. Chimneys exhibited marked differences
      in vent fluid geochemistry and microbial community composition, with structures
      being differentially dominated by gamma (gamma) or epsilon (epsilon)
      proteobacteria. Similarly, qPCR analyses of functional genes representing
      different carbon fixation pathways showed striking differences in gene abundance
      among chimney structures. Carbon fixation rates showed no obvious correlation
      with observed in situ vent fluid geochemistry, community composition or
      functional gene abundance. Together, these data reveal that (i) net anaerobic
      carbon fixation rates among these chimneys are elevated at lower temperatures,
      (ii) clear differences in community composition and gene abundance exist among
      chimney structures, and (iii) tremendous spatial heterogeneity within these
      environments likely confounds efforts to relate the observed rates to in situ
      microbial and geochemical factors. We also posit that microbes typically thought
      to be mesophiles are likely active and growing at cooler temperatures, and that
      their activity at these temperatures comprises the majority of endolithic
      anaerobic primary production in hydrothermal vent chimneys.

PMID- 23551688
TI  - Complication and failure rates with implant-supported fixed dental prostheses and
      single crowns: a 10-year retrospective study.
AB  - PURPOSE: Clinical studies related to the long-term outcomes with implant
      supported reconstructions are still sparse. The aim of this 10-year retrospective
      study was to assess the rate of mechanical/technical complications and failures
      with implant supported fixed dental prostheses (FDPs) and single crowns (SCs) in
      a large cohort of partially edentulous patients. MATERIALS AND METHODS: The
      comprehensive multidisciplinary examination consisted of a medical/dental
      history, clinical examination, and a radiographic analysis. Prosthodontic
      examination evaluated the implant-supported reconstructions for
      mechanical/technical complications and failures, occlusal analysis,
      presence/absence of attrition, and location, extension, and retention type.
      RESULTS: Out of three hundred ninety seven fixed reconstructions in three hundred
      three patients, two hundred sixty eight were SCs and one hundred twenty seven
      were FDPs. Of these three hundred ninety seven implant-supported reconstructions,
      18 had failed, yielding a failure rate of 4.5% and a survival rate of 95.5% after
      a mean observation period of 10.75 years (range: 8.4-13.5 years). The most
      frequent complication was ceramic chipping (20.31%) followed by occlusal screw
      loosening (2.57%) and loss of retention (2.06%). No occlusal screw fracture, one
      abutment loosening, and two abutment fractures were noted. This resulted in a
      total mechanical/technical complication rate of 24.7%. The prosthetic success
      rate over a mean follow-up time of 10.75 years was 70.8%. Generalized attrition
      and FDPs were associated with statistically significantly higher rates of ceramic
      fractures when compared with SCs. Cantilever extensions, screw retention,
      anterior versus posterior, and gender did not influence the chipping rate.
      CONCLUSIONS: After a mean exposure time of 10.75 years, high survival rates for
      reconstructions supported by Sand-blasted Large-grit Acid-etched implants can be
      expected. Ceramic chipping was the most frequent complication and was increased
      in dentitions with attrition and in FDPs compared with SCs.

PMID- 23551689
TI  - Fatal human metapneumovirus infection following allogeneic hematopoietic stem
      cell transplantation.
AB  - Respiratory viruses are an important yet underestimated cause of infectious
      morbidity and mortality in immunocompromised children and adolescents. Here, we
      report the occurrence of fatal lower respiratory tract disease associated with
      human metapneumovirus (HMPV) infection in a 10-year-old girl with chronic graft
      versus-host disease following allogeneic hematopoietic stem cell transplantation
      (HSCT) for secondary chronic myeloid leukemia. Symptoms occurred 8 months after
      HSCT while on immunosuppression with 0.2 mg/kg/day of prednisone, and presented
      as dry cough, bilateral pneumonitis, and progressive respiratory distress. Non
      invasive and invasive microbiological investigations revealed HMPV type B as the
      sole pathogen. Histopathological findings showed interstitial and intra-alveolar
      pneumonitis with profound alveolar cell damage. The patient was treated with
      intravenous and oral ribavirin and polyvalent immunoglobulins, but ultimately
      died from respiratory failure. The case reflects the potentially fatal impact of
      infections by respiratory viruses in immunocompromised patients and the need for
      effective approaches to their prevention and treatment.

PMID- 23551690
TI  - Administration of MS-275 improves cognitive performance and reduces cell death
      following traumatic brain injury in rats.
AB  - AIMS: The MS-275 is a selective inhibitor of class I histone deacetylases
      (HDACs), which has been reported as a potential strategy in some central nervous
      system diseases associated with neurodegeneration and disturbed learning.
      However, its role in traumatic brain injury is not well defined. In this study,
      we examined the behavioral-cognitive performance as well as histology outcome in
      adult rats to evaluate whether postinjury administration of MS-275 (15 and 45
      mg/kg) would provide neuroprotection benefits and ameliorate cognitive deficits
      following fluid percussion injury. METHODS: Traumatic brain injury (~2.15 ATMs)
      was produced using a fluid percussion device with the lateral orientation. MS-275
      was administered (15 and 45 mg/kg) systemically once daily for 7 days starting at
      30 min after lateral fluid percussion TBI. Acquisition of spatial learning and
      memory retention was assessed using the Morris water maze (MWM) on days 10-14
      after TBI. Brain tissues were collected and stained with Fluoro-Jade B
      histofluorescence (for degenerating neurons) at 24 h after injury and cresyl
      violet (for long-term neuronal survival) on day 14 postinjury. RESULTS:
      Behavioral outcome after TBI revealed MS-275 treatment groups, at all doses
      examined, performed significantly better in the Morris Water Maze (P < 0.001).
      Acute histology analysis demonstrated that 45 mg/kg MS-275 significantly reduced
      the number of degenerating neurons in the ipsilateral CA2-3 hippocampus at 24 h
      postinjury (P = 0.007). There was a trend for MS-275 to increase the survival of
      neurons in the CA2-3 hippocampus on 14 days after TBI (P = 0.164). CONCLUSION:
      Our present data highlight the fact that MS-275 may provide neuroprotective
      effect and improve cognitive performance after TBI. We concluded that MS-275 is a
      potential novel treatment and will have an ameliorative effect on some of the
      pathological features associated with TBI.

PMID- 23551691
TI  - Overexpression of Hippo pathway effector TAZ in tongue squamous cell carcinoma:
      correlation with clinicopathological features and patients' prognosis.
AB  - BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) is a key
      downstream effector of Hippo signaling pathway involved in stem cell
      differentiation and organ development. Recently, its deregulation has been linked
      to initiation and progression of various cancers. The purpose of this study was
      to investigate the expression of TAZ in tongue squamous cell carcinoma (TSCC) and
      its prognostic value in predicting patients' outcomes. METHODS: TAZ expression
      and localization in a panel of TSCC cell lines and human immortalized oral
      epithelial cell (HIOEC) were determined by real-time RT-PCR, western blotting,
      and immunofluorescence. In 52 TSCC tumor specimens with detailed clinical and
      follow-up data, TAZ abundance was examined by immunohistochemistry and its
      associations with clinicopathological parameters, Ki-67 expression and patients'
      survival were further assessed. RESULTS: TAZ mRNA and protein levels were
      significantly higher in TSCC cells and specimens than those in non-cancerous
      cells and normal tongue mucosa. Overexpression of TAZ in TSCC was significantly
      associated with tumor size (P = 0.033), pathological grade (P = 0.026), clinical
      stage (P = 0.013), Ki-67 expression (P = 0.0485), and reduced overall and disease
      free survival (Kaplan-Meier analysis, log-rank test, P = 0.020, 0.019,
      respectively). Multivariate Cox regression analysis identified TAZ as an
      important independent predictor for survival of patients with TSCC [HR (hazard
      ratio), 4.351; 95% CI (95% confidence interval), 1.477-12.819; P = 0.008].
      CONCLUSION: Our data indicate that aberrant TAZ overexpression is associated with
      key clinicopathological features and poor survival in TSCC. These results suggest
      that TAZ might play critical roles in tumorigenesis of TSCC and become a novel
      prognostic biomarker and potential therapeutic target for this malignancy.

PMID- 23551692
TI  - Esophageal polyps in pediatric patients undergoing routine diagnostic upper
      gastrointestinal endoscopy: a multicenter study.
AB  - Esophageal polyps are uncommon findings in pediatric patients, and reports have
      been limited to case reports. Esophageal polyps have been previously ascribed to
      esophagitis secondary to gastroesophageal reflux, medications, infections and
      recurrent vomiting. They have been associated with underlying conditions such as
      hiatal hernia, Barrett's esophagus, eosinophilic esophagitis and Crohn's disease.
      Presenting complaints of children with esophageal polyps have included vomiting,
      dysphagia, hematemesis and abdominal pain. The aim of this paper is to
      characterize the incidence, clinical presentation and progression, histologic
      subtypes and associated mucosal abnormalities in children with esophageal polyps.
      A retrospective multicenter study was performed at four institutions identifying
      diagnosis of esophageal polyps in pediatric patients (<21 years). Information was
      obtained from patient charts, endoscopy reports and histopathology reports.
      Specimens and slides were examined by experienced pediatric pathologists for all
      included cases. Esophageal polyps were identified in 13 patients (9 M) from 9438
      esophagogastroduodenoscopies (0.14%). Mean age of subjects was 9.2 years.
      Vomiting was the most common indication for endoscopy. Polyp location was at the
      gastroesophageal junction in 7 of the 13 cases. Most polyps were inflammatory (n
      = 7). Esophagitis was noted in 69% of those with esophageal polyps. Repeat
      endoscopies in six patients at a mean interval of 8 months noted persistence of
      polyps in all six patients. This paper is the first to characterize esophageal
      polyps in pediatrics. These polyps are rare in children and often are associated
      with esophagitis. Presenting complaints seem to vary by age. Polyps did not
      consistently change with either time or acid suppression. The optimal management
      strategy has yet to be defined and likely depends on the underlying
      pathophysiologic process.

PMID- 23551693
TI  - Phase 1 prospective evaluation of the oncological adequacy of robotic assisted
      video-endoscopic inguinal lymphadenectomy in patients with penile carcinoma.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Several lymph node
      staging strategies have been proposed as a response to the high morbidity seen
      after standard inguinal lymphadenectomy for penile cancer. A video-endoscopic
      (laparoscopic and robotic) approach has been proposed as a less morbid procedure
      in several retrospective studies. To date, none has evaluated the oncological
      adequacy with regard to whether all relevant nodes have been removed. To the
      authors' knowledge this is the first prospective study of a robotic or
      laparoscopic inguinal lymphadenectomy that evaluates the oncological adequacy of
      this approach for penile cancer. The study shows that robotic inguinal
      lymphadenectomy allowed adequate staging of disease in the inguinal region by
      removing all relevant lymph nodes as assessed by an independent evaluating
      urological oncologist. OBJECTIVE: To prospectively determine the oncological
      adequacy of robotic assisted video-endoscopic inguinal lymphadenectomy (RAVEIL).
      PATIENTS AND METHODS: Patients with T1-3N0 penile cancer were enrolled into a
      prospective phase I trial at a tertiary care institution from March 2010 to
      January 2012. All patients underwent an initial RAVEIL approach. Verification of
      adequacy of dissection was performed by an independent surgeon via a separate
      open incision at the conclusion of the RAVEIL procedure. Out of 10 patients, if
      more than two superficial inguinal fields with >=2 nodes or more than four with
      >=1 node remained within the superficial dissection field, the study would not
      proceed to phase II. RESULTS: Of 10 enrolled patients two had inguinal metastases
      and all positive nodes were detected by RAVEIL. The remaining eight patients had
      no metastases, with a mean of nine (range 5-21) left and nine (range 6-17) right
      nodes removed. One inguinal field RAVEIL was converted to an open dissection. The
      verifying surgeon confirmed that 18 of 19 inguinal fields (94.7% in nine
      patients) had an adequate dissection. Two benign nodes were found just beneath
      Scarpa's fascia above the inguinal dissection field. Limitations of the study
      include an inability to determine decisively what specific wound complications
      were related to RAVEIL because of the protocol-specified creation of a small
      inguinal incision for verification of adequate dissection. CONCLUSION: RAVEIL
      allowed adequate staging of disease in the inguinal region among patients with
      penile cancer at risk for inguinal metastases.

PMID- 23551694
TI  - An absolute atrial arrhythmia: what is the mechanism?

PMID- 23551695
TI  - Construct validity and reliability of the Handover Evaluation Scale.
AB  - AIMS AND OBJECTIVES: To examine the psychometric properties of the Handover
      Evaluation Scale using exploratory and confirmatory factor analysis. BACKGROUND:
      Handover is a fundamental component of clinical practice and is essential to
      ensure safe patient care. Research indicates a number of problems with this
      process, with high variability in the type of information provided. Despite the
      reported deficits with handover practices internationally, guidelines and
      standardised tools for its conduct and evaluation are scarce. Further work is
      required to develop an instrument that measures the effectiveness of handover in
      a valid and reliable way. DESIGN: Secondary analysis of data collected between
      2006-2008 from nurses working on 24 wards across a large Australian healthcare
      service. METHODS: A sample of 299 nurses completed the survey that included 20
      self-report items which evaluated the effectiveness of handover. Data were
      analysed using exploratory factor analysis and confirmatory factor analysis
      supported by structural equation modelling. RESULTS: Analyses resulted in a 14
      item Handover Evaluation Scale with three subscales: (1) quality of information
      (six items), (2) interaction and support (five items) and (3) efficiency (three
      items). A fourth subscale, patient involvement (three items), was removed from
      the scale as it was not a good measure of handover. CONCLUSIONS: The scale is a
      self-report, valid and reliable measure of the handover process. It provides a
      useful tool for monitoring and evaluating handover processes in health
      organisations, and it is recommended for use and further development. RELEVANCE
      TO CLINICAL PRACTICE: Monitoring handover is an important quality assurance
      process that is required to meet healthcare standards. This reliable and valid
      scale can be used in practice to monitor the quality of handover and provide
      information that can form the basis of education and training packages and
      guidelines to improve handover policies and processes.

PMID- 23551696
TI  - Disparities in initial presentation and treatment outcomes of diabetic foot
      ulcers in a public, private, and Veterans Administration hospital.
AB  - BACKGROUND: Disparities in diabetic foot ulcer (DFU) treatment outcomes are well
      described, although few studies identify risk factors contributing to disparate
      healing and amputation rates. In a unique academic center serving urban public,
      private, and veteran patients, we investigated amputation and healing rates and
      specific risk factors for disparate treatment outcomes. METHODS: A retrospective
      chart review of diabetic patients with a new diagnosis of a foot ulcer at
      geographically adjacent, but independent public, private, and Veterans
      Administration (VA) hospitals was conducted. Healing and lower extremity
      amputation outcomes were assessed. RESULTS: Across the three hospitals, 234
      patients met the inclusion criteria. Patients at the VA hospital were older (mean
      72.5 years; P < 0.001) and had gangrenous ulcers (mean 14.1%; P < 0.001) compared
      with patients in the private and public hospitals. Public hospital patients were
      mostly Hispanic (mean 54%; P < 0.001) with a shorter duration of diabetes (mean
      12.8 years; P = 0.02), but were more poorly controlled than VA and private
      hospital patients (P <= 0.001). Prior amputation (odds ratio [OR] 1.97; P =
      0.016) and non-Caucasian race (OR 2.42; P = 0.004) increased the risk of
      amputation on multivariate analysis. Osteomyelitis (P = 0.0371) and gangrene (P <
      0.001) are independent risk factors for amputation. Across all three hospitals,
      42.3% of patients were treated by amputation (6.8% private, 12% public and 23.5%
      VA; P < 0.001). CONCLUSION: In a single triumvirate health care system where the
      patient population is stratified primarily by insurance, VA patients have
      significantly higher amputation rates compared with patients at adjacent private
      and public hospitals. The VA patients are largely racial minorities with advanced
      DFU progression to gangrenous ulcers.

PMID- 23551697
TI  - Left atrial volume as predictor of valve replacement and cardiovascular events in
      patients with asymptomatic mild to moderate aortic stenosis.
AB  - BACKGROUND: Left atrial (LA) size is known to increase with chronically increased
      left ventricular (LV) filling pressure. We hypothesized that LA volume was
      predictive of aortic valve replacement (AVR) and cardiovascular events in a large
      cohort of patients with asymptomatic mild to moderate aortic valve stenosis.
      METHODS: Transthoracic echocardiography was performed in 1,758 patients in the
      Simvastatin and Ezetemibe in Aortic Stenosis study. LA volume was measured in the
      apical four-chamber view in 1,503 patients (85%). The relation of LA volume to
      AVR or a combined endpoint of cardiovascular events (AVR, congestive heart
      failure due to aortic stenosis or death from cardiovascular causes) was
      evaluated. RESULTS: AVR was performed in 415 (28%) patients, whereas 505 (34%)
      reached the combined endpoint. A significant but weak association of increased LA
      volume and risk of the combined endpoint was found (log-rank test: P = 0.02), but
      this relation did not reach any significance in a multivariate model adjusting
      for age, gender, aortic valve area index, LV ejection fraction, LV hypertrophy,
      hypertension, and mitral regurgitation. LA volume was not predictive of AVR (log
      rank test: P = 0.3). CONCLUSION: In asymptomatic patients with mild to moderate
      Aortic valve stenosis (AS), LA volume was not predictive of the combined endpoint
      of Aortic valve replacement, development of heart failure or cardiac death. AVA
      and presence of LV hypertrophy were the only predictors of events in multivariate
      analysis.

PMID- 23551698
TI  - Physicochemical interpretation of acid-base abnormalities in 54 adult horses with
      acute severe colitis and diarrhea.
AB  - BACKGROUND: The quantitative effect of strong electrolytes, pCO2 , and plasma
      protein concentration in determining plasma pH and bicarbonate concentrations can
      be demonstrated with the physicochemical approach. Plasma anion gap (AG) and
      strong ion gap (SIG) are used to assess the presence or absence of unmeasured
      anions. HYPOTHESES: The physicochemical approach is useful for detection and
      explanation of acid-base disorders in horses with colitis. AG and SIG accurately
      predict hyperlactatemia in horses with colitis. ANIMALS: Fifty-four horses with
      acute colitis and diarrhea. METHODS: Retrospective study. Physicochemical
      variables were calculated for each patient. ROC curves were generated to analyze
      sensitivity and specificity of AG and SIG for predicting hyperlactatemia.
      RESULTS: Physicochemical interpretation of acid-base events indicated that strong
      ion metabolic acidosis was present in 39 (72%) horses. Mixed strong ion acidosis
      and decreased weak acid (hypoproteinemia) alkalosis was concomitantly present in
      17 (30%) patients. The sensitivity and specificity of AG and SIG to predict
      hyperlactatemia (L-lactate > 5 mEq/L) were 100% (95% CI, 66.4-100; P < .0001) and
      84.4% (95% CI, 70.5-93.5 P < .0001). Area under the ROC curve for AG and SIG for
      predicting hyperlactatemia was 0.95 (95% CI, 0.86-0.99) and 0.93 (95% CI, 0.83
      0.99), respectively. CONCLUSION AND CLINICAL RELEVANCE: These results emphasize
      the importance of strong ions and proteins in the maintenance of the acid-base
      equilibria. AG and SIG were considered good predictors of clinically relevant
      hyperlactatemia.

PMID- 23551699
TI  - Severe infections caused by Panton-Valentine leukocidin-positive Staphylococcus
      aureus in infants: report of three cases and review of literature.
AB  - We report three cases of severe infections in infants caused by Panton-Valentine
      leukocidin positive Staphylococcus aureus and evolved with a positive outcome.
      The literature of Panton-Valentine leukocidin positive Staphylococcus aureus
      infections in infants is reviewed. CONCLUSION: Our findings suggest that a prompt
      identification of Panton-Valentine leukocidin positive Staphylococcus aureus and
      an appropriate therapy can reduce mortality and long-term sequelae. Further
      research is needed to specify features of Panton-Valentine leukocidin positive
      Staphylococcus aureus infections in infants.

PMID- 23551700
TI  - Assessing treatment response after induction Bacillus Calmette-Guerin for
      carcinoma in situ of the urinary bladder: can post-induction random bladder
      biopsies be avoided?
AB  - OBJECTIVES: Patients diagnosed with bladder carcinoma in situ (CIS) and treated
      with intravesical Bacillus Calmette-Guerin (BCG) often undergo post-induction
      random bladder biopsies to assess treatment response. We sought to determine the
      correlation between post-induction urinary cytology/cystoscopy and
      histopathological findings obtained by random bladder biopsies. METHODS: Patients
      who were treated with BCG between 2006 and 2010 for CIS, had surveillance
      cystoscopy and cytology, and subsequently underwent random bladder biopsies were
      selected for analysis. Patients with a history of or concomitant urothelial cell
      carcinoma (UCC) stage T1 or higher were excluded. Cystoscopic finings were
      characterized as follows: negative - no mucosal erythema, raised lesions or
      papillary tumours; suspicious - mucosal erythema, but no raised lesions or
      papillary tumours; and positive - sessile or papillary tumours. The accuracy of
      cytology in predicting the results of subsequent random bladder biopsies was
      analysed. RESULTS: Of 21 patients included, surveillance cystoscopy findings were
      characterized as negative in nine, suspicious in seven and positive in five. Of
      16 patients with negative/suspicious cystoscopy, 13 had agreement between
      cytology and biopsy, nine of whom were negative and four positive. Three of 16
      patients had positive cytology, but negative biopsies; on further investigation
      of these three, one had CIS and two subsequent UCC. In the positive cystoscopy
      group, four of five patients had agreement between cytology and biopsy, two of
      whom were negative and two positive. One of the five patients had negative
      cytology, but a positive biopsy. CONCLUSION: Our data suggest foregoing random
      bladder biopsies in patients with negative urine cytology and no evidence of
      intravesical recurrence on cystoscopy following an induction course of BCG for
      CIS of the urinary bladder.

PMID- 23551701
TI  - Antibiotic resistance in human peri-implantitis microbiota.
AB  - OBJECTIVES: Because antimicrobial therapy is often employed in the treatment of
      infectious dental implant complications, this study determined the occurrence of
      in vitro antibiotic resistance among putative peri-implantitis bacterial
      pathogens. METHODS: Submucosal biofilm specimens were cultured from 160 dental
      implants with peri-implantitis in 120 adults, with isolated putative pathogens
      identified to species level, and tested in vitro for susceptibility to 4 mg/l of
      doxycycline, 8 mg/l of amoxicillin, 16 mg/l of metronidazole, and 4 mg/l of
      clindamycin. Findings for amoxicillin and metronidazole were combined post-hoc to
      identify peri-implantitis species resistant to both antibiotics. Gram-negative
      enteric rods/pseudomonads were subjected to ciprofloxacin disk diffusion testing.
      RESULTS: One or more cultivable submucosal bacterial pathogens, most often
      Prevotella intermedia/nigrescens or Streptococcus constellatus, were resistant in
      vitro to clindamycin, amoxicillin, doxycycline, or metronidazole in 46.7%, 39.2%,
      25%, and 21.7% of the peri-implantitis subjects, respectively. Only 6.7% subjects
      revealed submucosal test species resistant in vitro to both amoxicillin and
      metronidazole, which were either S. constellatus (one subject) or ciprofloxacin
      susceptible strains of gram-negative enteric rods/pseudomonads (seven subjects).
      Overall, 71.7% of the 120 peri-implantitis subjects exhibited submucosal
      bacterial pathogens resistant in vitro to one or more of the tested antibiotics.
      CONCLUSIONS: Peri-implantitis patients frequently yielded submucosal bacterial
      pathogens resistant in vitro to individual therapeutic concentrations of
      clindamycin, amoxicillin, doxycycline, or metronidazole, but only rarely to both
      amoxicillin and metronidazole. Due to the wide variation in observed drug
      resistance patterns, antibiotic susceptibility testing of cultivable submucosal
      bacterial pathogens may aid in the selection of antimicrobial therapy for peri
      implantitis patients.

PMID- 23551702
TI  - Whole-exome targeted sequencing of the uncharacterized pine genome.
AB  - The large genome size of many species hinders the development and application of
      genomic tools to study them. For instance, loblolly pine (Pinus taeda L.), an
      ecologically and economically important conifer, has a large and yet
      uncharacterized genome of 21.7 Gbp. To characterize the pine genome, we performed
      exome capture and sequencing of 14 729 genes derived from an assembly of
      expressed sequence tags. Efficiency of sequence capture was evaluated and shown
      to be similar across samples with increasing levels of complexity, including
      haploid cDNA, haploid genomic DNA and diploid genomic DNA. However, this
      efficiency was severely reduced for probes that overlapped multiple exons,
      presumably because intron sequences hindered probe:exon hybridizations. Such
      regions could not be entirely avoided during probe design, because of the lack of
      a reference sequence. To improve the throughput and reduce the cost of sequence
      capture, a method to multiplex the analysis of up to eight samples was developed.
      Sequence data showed that multiplexed capture was reproducible among 24 haploid
      samples, and can be applied for high-throughput analysis of targeted genes in
      large populations. Captured sequences were de novo assembled, resulting in 11 396
      expanded and annotated gene models, significantly improving the knowledge about
      the pine gene space. Interspecific capture was also evaluated with over 98% of
      all probes designed from P. taeda that were efficient in sequence capture, were
      also suitable for analysis of the related species Pinus elliottii Engelm.

PMID- 23551704
TI  - Hip protectors: are they beneficial in protecting older people from fall-related
      injuries?
AB  - AIMS AND OBJECTIVES: To report findings of an investigation into the
      methodological quality of research informing the use of hip protectors for those
      clients in residential aged care considered to be at high risk of falls and to
      contribute to the translation of research evidence into practice by identifying
      issues surrounding the use of hip protectors in practice. BACKGROUND: Falls risk
      is a predominant concern when nursing older people, especially those in
      residential aged care. Fall-related injuries, specifically pertaining to the hip,
      yield a high cost to the individual both physically and psychologically.
      Accordingly, hip protectors are argued in related literature as a form of
      protection against such injuries. DESIGN: A database search as per a specified
      search strategy was conducted for quantitative research publications and
      randomised control trials. METHODS: English language publications were sought
      from the year 2000-2011. Searches were made, using specific combinations of
      keywords, in the following databases: MEDLINE via OvidSP, CINAHL via EBSCOHost,
      Ageline via OvidSP, Cochrane Library, The Joanna Briggs Institute and Google
      Scholar. RESULTS: Six articles were selected for review. Methodological quality
      of the research publications collated varied, and the use of hip protectors was
      deemed inconclusive. Compliance was raised as a prevailing issue. CONCLUSION: The
      problem of fall-related injuries is significant. Whilst some evidence is
      inconclusive, the use of hip protectors is recommended as best practice.
      RELEVANCE TO CLINICAL PRACTICE: The issue of compliance, however, was identified
      to affect the use of appliances in residential aged care. Addressing compliance
      issues must be tackled if hip protectors are to be part of a resident-centred
      approach.

PMID- 23551705
TI  - Comparison of marginal fidelity and surface roughness of porcelain veneers
      fabricated by refractory die and pressing techniques.
AB  - PURPOSE: The aim of the present study was to compare the marginal fidelity and
      surface roughness of porcelain veneers fabricated by the refractory die and
      pressing techniques under in vivo conditions. MATERIALS AND METHODS: A total of
      72 veneers were prepared for anterior teeth in 12 participants. Veneers on
      anterior teeth in the first and second quadrants were fabricated using refractory
      die (group I) and pressing techniques (group II), respectively. Surface roughness
      was evaluated using a profilometer in three areas (cervical, mesio-incisal, disto
      incisal) for each veneer. Marginal adaptation of all the veneers (N = 36/group)
      was evaluated at each margin (cervical, incisal, mesial, and distal) at 7 days
      and at 3 months after cementation under a scanning electron microscope (SEM) at
      200* magnification. RESULTS: The mean surface roughness of veneers in cervical,
      mesio-incisal, and disto-incisal areas was 0.41 +/- 0.25, 0.33 +/- 0.14, and 0.32
      +/- 0.14 MUm, respectively, for group I; and 0.31 +/- 0.11, 0.36 +/- 0.18, and
      0.29 +/- 0.11 MUm, respectively, for group II. Intra- and intergroup comparisons
      showed no statistically significant values for all areas (p > 0.05). In 144
      margins evaluated for each group, a visible gap was present in 15 (10.4%) and 18
      (12.5%) recordings at 7 days for groups I and II, respectively. They increased to
      19 (13.1%) and 20 (13.8%) after 3 months. These gaps were further broken down
      into percent distribution of total recordings at the cervical, incisal, mesial,
      and distal margins. Intragroup comparison was made using the Cochrane test. The
      chi-square test and Fisher's exact test were used for intergroup comparison of
      margins, revealing no statistical difference (p > 0.05) CONCLUSION: Within the
      limitations of the study, the surface roughness and marginal fidelity of
      porcelain veneers fabricated by refractory die technique and pressing technique
      were comparable.

PMID- 23551706
TI  - Fresh and preserved green fodder modify effects of urinary acidifiers on urine pH
      of horses.
AB  - Hay stabilises urine pH in horses. It is unknown whether this is an effect of
      structure or of chemical composition. In this study, four ponies (230-384 kg body
      weight [BW]) were fed six different diets with either a structure or a
      composition similar to hay with and without acidifiers in a cross-over
      experimental design in amounts to maintain body weight with the following main
      compounds: Fresh grass (GRASS), alfalfa hay (ALF), grass cobs (COBS), grass
      silage (SIL), straw (STR) or extruded straw (STRe) for 2 to 10 days. Urine pH was
      measured in all trials, blood pH, blood base excess and bicarbonate as well as
      mineral balance were determined in GRASS, ALF, STR and STRe. In the trials with
      straw and extruded straw, urine pH decreased significantly (STR control: 7.8 +/-
      0.23, acidifier: 5.2 +/- 0.38) when acidifiers were added, whereas in all other
      diets that were based on fresh or preserved green fodder, pH did not decrease
      below 7. Blood pH was similarly affected by diet and acidifiers. Acidifiers had
      little effect on the pre-prandial blood pH, only in diet STR there was a
      significant reduction in relation to control. Post-prandial blood pH was
      significantly reduced by acidifiers in all diets. Blood bicarbonate and base
      excess showed corresponding effects. Faecal and renal mineral excretion and
      apparent mineral digestibility were not systematically affected by diet or
      acidifiers except for chloride. Chloride added as inorganic chloride salt had an
      even better apparent digestibility than chloride originating from feed. Because
      only green plant material stabilised acid base balance, chlorophyll and its
      metabolites are discussed as potential mediators of the effect of green fodder on
      acid base balance.

PMID- 23551708
TI  - Salvage radiation therapy and chemoradiation therapy for postoperative
      locoregional recurrence of esophageal cancer.
AB  - The purpose of this retrospective study was to assess the efficacy of salvage
      radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional
      recurrence (LR) of esophageal cancer after curative surgery. Forty-two patients
      who received salvage RT or CRT for LR of esophageal cancer after curative surgery
      between November 2000 and May 2012 were reviewed. The intended RT regimen was 60
      Gy in 30 fractions combined with concurrent platinum-based chemotherapy. Median
      follow-up periods were 17.9 months for all evaluable patients and 28.2 months for
      patients still alive (19 patients) at analysis time. The 1-, 2-, and 3-year
      survival rates were 81.2 +/- 6.4%, 51.3 +/- 8.6%, and 41.1 +/- 8.7%,
      respectively, with a median survival time of 24.3 +/- 4.1 months. Out of 41
      evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage
      therapy. However, univariate analyses for overall survival showed no significant
      prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the
      patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe
      and effective. These therapies may offer long-term survival to some patients. RT
      or CRT should be considered for LR. 

PMID- 23551703
TI  - Microbial life associated with low-temperature alteration of ultramafic rocks in
      the Leka ophiolite complex.
AB  - Water-rock interactions in ultramafic lithosphere generate reduced chemical
      species such as hydrogen that can fuel subsurface microbial communities. Sampling
      of this environment is expensive and technically demanding. However, highly
      accessible, uplifted oceanic lithospheres emplaced onto continental margins
      (ophiolites) are potential model systems for studies of the subsurface biosphere
      in ultramafic rocks. Here, we describe a microbiological investigation of
      partially serpentinized dunite from the Leka ophiolite (Norway). We analysed
      samples of mineral coatings on subsurface fracture surfaces from different depths
      (10-160 cm) and groundwater from a 50-m-deep borehole that penetrates several
      major fracture zones in the rock. The samples are suggested to represent
      subsurface habitats ranging from highly anaerobic to aerobic conditions. Water
      from a surface pond was analysed for comparison. To explore the microbial
      diversity and to make assessments about potential metabolisms, the samples were
      analysed by microscopy, construction of small subunit ribosomal RNA gene clone
      libraries, culturing and quantitative-PCR. Different microbial communities were
      observed in the groundwater, the fracture-coating material and the surface water,
      indicating that distinct microbial ecosystems exist in the rock. Close relatives
      of hydrogen-oxidizing Hydrogenophaga dominated (30% of the bacterial clones) in
      the oxic groundwater, indicating that microbial communities in ultramafic rocks
      at Leka could partially be driven by H2 produced by low-temperature water-rock
      reactions. Heterotrophic organisms, including close relatives of hydrocarbon
      degraders possibly feeding on products from Fischer-Tropsch-type reactions,
      dominated in the fracture-coating material. Putative hydrogen-, ammonia-,
      manganese- and iron-oxidizers were also detected in fracture coatings and the
      groundwater. The microbial communities reflect the existence of different
      subsurface redox conditions generated by differences in fracture size and
      distribution, and mixing of fluids. The particularly dense microbial communities
      in the shallow fracture coatings seem to be fuelled by both photosynthesis and
      oxidation of reduced chemical species produced by water-rock reactions.

PMID- 23551709
TI  - Granulocyte-colony stimulating factor-producing cervical cancers treated with
      carbon-ion irradiation.
AB  - Granulocyte-colony stimulating factor (G-CSF)-producing tumor is a rare
      condition. It has an aggressive nature and shows resistance to conventional
      treatments. We report two cases of G-CSF-producing uterine cervical cancer who
      were successfully treated with carbon-ion radiotherapy (C-ion RT). The first case
      was a 76-year-old woman with stage IIIB uterine cervical cancer, and the second
      was a 75-year-old woman with bulky stage IIB disease. Prior to treatment, both
      patients presented severe granulocytosis and elevated serum G-CSF concentrations.
      After C-ion RT, their cervical tumors completely disappeared, and their
      granulocytosis and elevated serum G-CSF levels improved as well. C-ion RT has
      been reported to be effective for various aggressive tumors, and it may be a good
      treatment option for this rare aggressive tumor.

PMID- 23551710
TI  - Serum proinflammatory cytokine responses to influenza virus vaccine among women
      during pregnancy versus non-pregnancy.
AB  - OBJECTIVE: This study aimed to comprehensively describe inflammatory responses to
      trivalent influenza virus vaccine (TIV) among pregnant women and determine
      whether responses differ compared to non-pregnancy. METHODS: Twenty-eight
      pregnant and 28 non-pregnant women were vaccinated. Serum cytokines were measured
      at baseline, and 1, 2, and 3 days post-vaccination. Anti-influenza antibody
      titers were measured at baseline and 1 month post-vaccination. RESULTS: Overall,
      following vaccination, tumor necrosis factor (TNF)-alpha and interleukin(IL)-6
      increased significantly, peaking at 1 day post-vaccination (P's < 0.001).
      Pregnant versus non-pregnant women showed no differences in IL-6, TNF-alpha, or
      IL-1beta responses. Pregnant women showed no change in IL-8 and increases in
      migration inhibitory factor (MIF), while non-pregnant showed decreases in both.
      Pregnancy did not significantly alter antibody responses. CONCLUSIONS:
      Inflammatory responses to TIV are mild, transient, and generally similar in
      pregnant and non-pregnant women. Given the variability evidenced, vaccination may
      provide a useful model for studying individual differences in inflammatory
      response propensity.

PMID- 23551711
TI  - Sexual dysfunction in men suffering from genital warts.
AB  - INTRODUCTION: Human papillomavirus (HPV) infection can present clinically as
      genital warts (GWs) in both males and females. Much less is known about the
      psychosexual consequences of GW, and the studies on patients in this group are
      still quite limited. AIMS: The aim of this study was to test two hypotheses: (i)
      sexual dysfunction (SD) is likely to occur in male patients suffering from GWs;
      (ii) if male SD exists, it may be associated with depression or anxiety. METHODS:
      This was a pilot study with a prospective cross-sectional design. Male patients
      with GW (N for patient group = 116) were compared with male control cases (N for
      control group = 71) using the Arizona Sexual Experience Scale (ASEX), Beck
      Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). The participants
      were evaluated by a dermatologist and a psychiatrist, respectively. MAIN OUTCOME
      MEASURES: The associations between sexual dysfunction, depression, and anxiety
      among the participants were examined. RESULTS: There was no difference between
      the groups in terms of sociodemographic changes. Sexual dysfunction was found to
      be significantly more common in the patients than controls (P = 0.000 < 0.001).
      When the subscores of ASEX were evaluated, they were found to be statistically
      significant between the two groups (P = 0.000 < 0.001). BDI and BAI scores were
      statistically higher in the patient group than in controls, and there was a
      positive correlation between BDI and BAI scores with ASEX total and subscores (P
      = 0.000 < 0.001). CONCLUSIONS: Male patients with GW have higher rates of sexual
      dysfunction, depression, and anxiety when compared with the normal population.
      Men suffering from GW should be evaluated for possible sexual problems, besides
      depression and anxiety.

PMID- 23551712
TI  - Ganciclovir-resistant cytomegalovirus infection in transplanted patients: utility
      of drug monitoring.

PMID- 23551713
TI  - Precision of fit and retention force of cast non-precious-crowns on standard
      titanium implant-abutment with different design and height.
AB  - OBJECTIVE: The cost-effectiveness of cast nonprecious frameworks has increased
      their prevalence in cemented implant crowns. The purpose of this study was to
      assess the effect of the design and height of the retentive component of a
      standard titanium implant abutment on the fit, possible horizontal rotation and
      retention forces of cast nonprecious alloy crowns prior to cementation. MATERIALS
      AND METHODS: Two abutment designs were examined: Type A with a 6 degrees  taper
      and 8 antirotation planes (Straumann Tissue-Level RN) and Type B with a 7.5
      degrees  taper and 1 antirotation plane (SICace implant). Both types were
      analyzed using 60 crowns: 20 with a full abutment height (6 mm), 20 with a medium
      abutment height (4 mm), and 20 with a minimal (2.5 mm) abutment height. The
      marginal and internal fit and the degree of possible rotation were evaluated by
      using polyvinylsiloxane impressions under a light microscope (magnification of
      *50). To measure the retention force, a custom force-measuring device was
      employed. STATISTICAL ANALYSIS: one-sided Wilcoxon rank-sum tests with Bonferroni
      Holm corrections, Fisher's exact tests, and Spearman's rank correlation
      coefficient. RESULTS: Type A exhibited increased marginal gaps (primary end
      point: 55 +/- 20 MUm vs. 138 +/- 59 MUm, P < 0.001) but less rotation (P < 0.001)
      than Type B. The internal fit was also better for Type A than for Type B (P <
      0.001). The retention force of Type A (2.49 +/- 3.2 N) was higher (P = 0.019)
      than that of Type B (1.27 +/- 0.84 N). Reduction in abutment height did not
      affect the variables observed. CONCLUSION: Less-tapered abutments with more
      antirotation planes provide an increase in the retention force, which confines
      the horizontal rotation but widens the marginal gaps of the crowns. Thus, casting
      of nonprecious crowns with Type A abutments may result in clinically unfavorable
      marginal gaps.

PMID- 23551714
TI  - Why study erythropoietin in preterm infants?

PMID- 23551715
TI  - Preventive pediatric cardiology.

PMID- 23551716
TI  - In vitro and in vivo antimicrobial efficacy of essential oils and individual
      compounds against Phytophthora parasitica var. nicotianae.
AB  - AIM: To evaluate the antimicrobial effects of essential oils (EOs) from cassia,
      basil, geranium, lemongrass, cumin and thyme, as well as their major components,
      against Phytophthora parasitica var. nicotianae; to investigate morphological
      changes in hyphae and sporangia in response to treatment with cinnamaldehyde; and
      to further evaluate potential biocontrol capacities against tobacco black shank
      under greenhouse conditions. METHODS AND RESULTS: The results revealed that the
      extent of mycelial growth inhibition was primarily dependent on the composition
      and concentration of the EOs and the structure of individual compounds.
      Cinnamaldehyde had a significantly higher inhibitory effect on mycelial growth,
      formation of sporangia, and production and germination of zoospores in P.
      parasitica var. nicotianae in vitro, achieving complete inhibition of these
      phenotypes at 72, 36, 36 and 18 mg l(-1), respectively. Scanning electron
      microscopic observations revealed that cinnamaldehyde can cause considerable
      morphological degenerations of hyphae and sporangia such as cytoplasmic
      coagulation, shrivelled mycelia and sporangia aggregates and swelling and lysis
      of mycelia and sporangia walls. In vivo assays with cinnamaldehyde demonstrated
      that this compound afforded protective effect against tobacco black shank under
      greenhouse conditions in susceptible tobacco plants. CONCLUSIONS: The results of
      in vitro and in vivo bioassays, together with SEM imaging of the microstructure
      of P. parasitica var. nicotianae supported the possibility of using
      cinnamaldehyde as a potent natural biofungicide in the greenhouse. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study provides a theoretical basis for the
      potential use of cinnamaldehyde as commercial agents or lead compounds that can
      be exploited as commercial biofungicides in the protection of tobacco plants from
      P. parasitica var. nicotianae infection.

PMID- 23551717
TI  - What explains the distribution of doctors and nurses in different countries, and
      does it matter for health outcomes?
AB  - AIMS: To re-examine the form of the relationships between the global distribution
      of health professionals (physicians and nurses), gross national product per
      capita, female literacy, and infant and under-5 mortality rates reported in three
      papers by Robinson and Wharrad using more recent data. The secondary aim was to
      explore prior assumptions about the quality of the data, the homogeneity of the
      sample, and the form of the relationship. BACKGROUND: The analyses by Robinson
      and Wharrad did not take account of differences between developing and developed
      countries. Furthermore, the intervening years have seen changes in healthcare
      professional roles and their global distribution. Re-examination of these
      relationships is therefore timely. DESIGN: A secondary analysis of routinely
      collected data from international databases. METHODS: A database was constructed
      from Organisation for Economic Co-operation and Development, United Nations and
      World Bank sources on 177 countries for around 2005. Regression analyses were
      performed first with number of physicians and of nurses per 1000 population as
      dependent variables and gross national product per capita, female literacy rates,
      and the Gini coefficient as independent variables; and second with all those
      variables as independent variables and infant mortality, under-5 mortality rates,
      and maternal mortality rates as dependent variables. RESULTS: There were clear
      and interesting differences between richer (Organisation for Economic Co
      operation and Development) countries and developing countries in the coefficients
      and in the power of the equations. CONCLUSIONS: The importance of understanding
      the implications of carrying out cross-country analysis and the urgent need for
      standardization of definitions in datasets are emphasized.

PMID- 23551719
TI  - Combined exercise training in postmenopausal women: implications for vascular
      hemodynamics.

PMID- 23551718
TI  - Transcriptome profiling of hippocampal CA1 after early-life seizure-induced
      preconditioning may elucidate new genetic therapies for epilepsy.
AB  - Injury of the CA1 subregion induced by a single injection of kainic acid (1 * KA)
      in juvenile animals (P20) is attenuated in animals with two prior sustained
      neonatal seizures on P6 and P9. To identify gene candidates involved in the
      spatially protective effects produced by early-life conditioning seizures we
      profiled and compared the transcriptomes of CA1 subregions from control, 1 * KA-
      and 3 * KA-treated animals. More genes were regulated following 3 * KA (9.6%)
      than after 1 * KA (7.1%). Following 1 * KA, genes supporting oxidative stress,
      growth, development, inflammation and neurotransmission were upregulated (e.g.
      Cacng1, Nadsyn1, Kcng1, Aven, S100a4, GFAP, Vim, Hrsp12 and Grik1). After 3 * KA,
      protective genes were differentially over-expressed [e.g. Cat, Gpx7, Gad1,
      Hspa12A, Foxn1, adenosine A1 receptor, Ca(2+) adaptor and homeostasis proteins,
      Cacnb4, Atp2b2, anti-apoptotic Bcl-2 gene members, intracellular trafficking
      protein, Grasp and suppressor of cytokine signaling (Socs3)]. Distinct anti
      inflammatory interleukins (ILs) not observed in adult tissues [e.g. IL-6
      transducer, IL-23 and IL-33 or their receptors (IL-F2 )] were also over
      expressed. Several transcripts were validated by real-time polymerase chain
      reaction (QPCR) and immunohistochemistry. QPCR showed that casp 6 was increased
      after 1 * KA but reduced after 3 * KA; the pro-inflammatory gene Cox1 was either
      upregulated or unchanged after 1 * KA but reduced by ~70% after 3 * KA. Enhanced
      GFAP immunostaining following 1 * KA was selectively attenuated in the CA1
      subregion after 3 * KA. The observed differential transcriptional responses may
      contribute to early-life seizure-induced pre-conditioning and neuroprotection by
      reducing glutamate receptor-mediated Ca(2+) permeability of the hippocampus and
      redirecting inflammatory and apoptotic pathways. These changes could lead to new
      genetic therapies for epilepsy. 

PMID- 23551720
TI  - Attitudes of primary care providers and recommendations of home blood pressure
      monitoring--DocStyles, 2010.
AB  - To assess primary care providers' (PCPs) opinions related to recommending home
      blood pressure monitoring (HBPM) for their hypertensive patients, the authors
      analyzed a Web-based 2010 DocStyles survey, which included PCPs' demographics,
      health-related behaviors, recommendations on HBPM, views of patient knowledge,
      and use of continuing medical education. Of the 1254 PCPs who responded, 539 were
      family practitioners, 461 were internists, and 254 were nurse practitioners; 32%
      recommended HBPM to >=90% of their patients and 26% recommended it to <=40% of
      their patients. Nurse practitioners were significantly more likely to recommend
      HBPM than were internists (odds ratio, 0.55; 95% confidence interval, 0.40-0.78).
      The top reasons for not recommending HBPM were "patient can't afford it" and
      "patient doesn't need it." A total of 20% of PCPs indicated that their patients
      were poor to lower middle class; these PCPs were less likely to recommend HBPM to
      their patients than were those PCPs with most patients in higher economic
      classes. Additional efforts are needed to provide education to providers,
      especially physicians, about the benefits of HBPM in improved and cost-effective
      blood pressure control in the United States.

PMID- 23551721
TI  - Visual hallucinations related to angiotensin-converting enzyme inhibitor use:
      case reports and review.
AB  - Four patients experienced visual hallucinations that appear to have been
      precipitated by lisinopril. Other cases of visual hallucinations have been
      reported with other angiotensin-converting enzyme (ACE) inhibitors. Older
      patients, particularly those with a history of either dementia or mild cognitive
      impairment, may be at higher risk. Hallucinations resolved within 1 to 30 days
      after cessation of ACE inhibitors. Development of visual hallucinations after
      initiation of ACE inhibitors should prompt discontinuation of therapy. Visual
      hallucinations have been reported in one case involving an ARB. Visual
      hallucinations have not been associated with direct renin inhibitors.
      Consideration should be given to use of alternative, unrelated antihypertensive
      drug classes.

PMID- 23551722
TI  - The impact of cigarette smoking on 24-hour blood pressure, inflammatory and
      hemostatic activity, and cardiovascular risk in Japanese hypertensive patients.
AB  - The aim of the study was to assess the impact of current smoking on 24-hour blood
      pressure (BP) and inflammatory and hemostatic activity and thereby the incidence
      of cardiovascular disease (CVD) in Japanese hypertensive patients. A total of 810
      hypertensive patients (mean age 72 years; 38% men) were prospectively followed-up
      (2799 person-years). During the follow-up, 66 cases of CVD occurred (stroke, 55;
      myocardial infarction, 7; both, 4). At baseline, the current smokers (n=166) had
      higher levels of high-sensitivity C-reactive protein (hs-CRP) (0.21 mg/dL vs 0.14
      mg/dL) and plasminogen activator inhibitor-1 (PAI-1) (46.1 ng/mL vs 37.8 ng/mL;
      both P=.001), but not of 24-hour BP, compared with nonsmokers. Using a Cox
      regression analysis, current smoking was independently associated with an
      increased risk of CVD (hazard ratio [HR], 2.6; P<.01), and the risk was
      substantially higher in women (HR, 6.1; P<.001) than in men (HR, 1.4; P=.41). The
      CVD risk of current smokers was magnified when it was accompanied with high hs
      CRP (highest quartile range, >=0.40 mg/L) or PAI-1 levels (>=58.9 ng/mL) compared
      with that in smokers with low hs-CRP or PAI-1 levels (both P<.05). Among
      hypertensive patients, current smokers had increased risk of CVD events, and the
      increase was more prominent when accompanied by circulatory inflammatory and
      hemostatic abnormalities.

PMID- 23551723
TI  - Changes in vascular hemodynamics in older women following 16 weeks of combined
      aerobic and resistance training.
AB  - The purpose of this study was to determine whether combined (aerobic and
      anaerobic) training decreases blood pressure (BP) and improves vascular
      properties. Seventy-nine postmenopausal women were randomly assigned to 3 groups
      that trained at different frequencies. Maximum oxygen uptake, body composition,
      BP, and arterial elasticity were evaluated prior to training and after 16 weeks
      of training. There was a significant time effect (decrease) for resting systolic
      BP (SBP) and rate pressure product. Exercise SBP, diastolic BP (DBP), heart rate,
      and RPP also decreased. Changes in total vascular impedance were related to SBP
      and changes in systemic vascular resistance were related to changes in DBP
      independent of body composition changes. Our findings suggest that combined
      training reduces SBP and improves vascular properties and that combined training
      1 d/wk decreases BP similar to more frequent combined training. Training-induced
      changes in arterial resistance and impedance may be involved in inducing changes
      in BP.

PMID- 23551724
TI  - Efficacy/safety of a fixed-dose amlodipine/olmesartan medoxomil-based treatment
      regimen in hypertensive blacks and non-blacks with uncontrolled BP on prior
      antihypertensive monotherapy.
AB  - In this secondary analysis of a dose-titration study of patients with
      hypertension uncontrolled on prior monotherapy, blacks (n=234) and non-blacks
      (n=765) were switched to amlodipine (AML)/olmesartan medoxomil (OM) 5/20 mg, with
      uptitration every 4 weeks to AML/OM 5/40 mg and then AML/OM 10/40 mg to achieve a
      seated cuff blood pressure (SeBP) of <120/70 mm Hg. Hydrochlorothiazide 12.5 and
      25 mg could be added if SeBP was >=125/75 mm Hg. The cumulative proportions of
      patients achieving systolic SeBP <140 mm Hg (<130 mm Hg if diabetic) at 12 weeks
      were 71.6% for blacks and 77.2% for non-blacks. Mean SeBP change from baseline in
      blacks (mean baseline BP: 153.0/93.7 mm Hg) ranged from -11.7/-6.1 mm Hg for
      AML/OM 5/20 mg to -23.6/-12.9 mm Hg for AML/OM 10/40 mg +hydrochlorothiazide 25
      mg (all P<.0001). Antihypertensive efficacy was maintained throughout the 24-hour
      dosing interval. An AML/OM-based regimen was effective in blacks with
      hypertension uncontrolled on prior monotherapy.

PMID- 23551725
TI  - Rate and predictors of blood pressure control in a federal qualified health
      center in Michigan: a huge concern?
AB  - Hypertension (HTN) is particularly burdensome in low-income groups. Federal
      qualified health centers (FQHCs) provide care for low-income and medically
      underserved populations. To assess the rates and predictors of blood pressure
      (BP) control in an FQHC in Michigan, a retrospective analysis of all patients
      with HTN, coronary artery disease, and/or diabetes mellitus (DM) seen between
      January 2006 and December 2008 was conducted. Of 212 patients identified, 154 had
      a history of HTN and 122 had DM. BP control was achieved in 38.2% of the entire
      cohort and in 31.1% of patients with DM. The mean age was lower in patients with
      controlled BP in both the total population (P=.05) and the DM subgroup (P=.02). A
      logistic regression model found only female sex (odds ratio, 2.27; P=.02) to be
      associated with BP control and a trend towards an association of age with
      uncontrolled BP (odds ratio, 0.97; P=.06). BP control in nondiabetics was 47.8%
      vs 31.1% in diabetic patients (P=.02). We found that patients who attended the
      FQHC had a lower rate of BP control compared with the national average. Our study
      revealed a male sex disparity and significantly lower rate of BP control among DM
      patients.

PMID- 23551726
TI  - Hormones other than aldosterone may contribute to hypertension in 3 different
      subtypes of primary aldosteronism.
AB  - Blood pressure (BP) level is similar in patients with 3 subtypes of primary
      aldosteronism (PA), even though aldosterone levels may vary. Glucocorticoids and
      adrenomedullary hormones may be influenced and may contribute to hypertension in
      PA. The authors' objective was to investigate the influence of PA on adrenal
      gland secretion and the roles of these hormones in hypertension. Patients
      diagnosed with PA (229 cases) were enrolled and classified into 3 subgroups:
      aldosterone-producing adenoma (APA), unilateral nodular adrenal hyperplasia
      (UNAH), and idiopathic hyperaldosteronism (IHA). Patients with essential
      hypertension served as the control group (100 cases). Concentration of the above
      hormones was measured and compared between groups. Level of plasma
      adrenocorticotrophic hormone (ACTH) in patients with APA was significantly lower
      than that in patients with IHA (P<.001) and UNAH (P<0.5). The 24-hour urinary
      free cortisol and adrenomedullary hormone levels were highest in patients with
      IHA, lower in patients with APA, and lowest in patients with UNAH. Systolic BP
      level was positively correlated with 8 am plasma cortisol level (r=0.142, P=.039)
      and plasma ACTH level (r=0.383, P=.016). Cortisol and adrenomedullary hormones
      were different between PA subtypes and they might involve regulation of BP in
      those patients.

PMID- 23551727
TI  - Effects of add-on nebivolol on blood pressure and glucose parameters in
      hypertensive patients with prediabetes.
AB  - In this multicenter trial, the effects of nebivolol added to an angiotensin
      converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) were
      assessed in patients with hypertension (diastolic blood pressure [DBP] 80-110 mm
      Hg) and prediabetes (fasting blood glucose 100-125 mg/dL and/or 2-hour oral
      glucose tolerance test [OGTT] 140-199 mg/dL). After a 4-week run-in period (in
      which lisinopril [10 mg/d] or losartan [50 mg/d] treatment was initiated),
      patients with DBP 90-110 mm Hg were randomized (2:2:1) to 12-week, double-blind
      treatment with nebivolol (n=223; 5-40 mg/d), hydrochlorothiazide (HCTZ; n=212;
      12.5-25 mg/d), or placebo (n=102), titrated to achievement of 130/80 mm Hg. The
      primary outcome measure was DBP (last observation carried forward, intent to
      treat population); secondary measures included systolic blood pressure (SBP) and
      glucose levels. At baseline, overall mean values for body mass index,
      triglycerides, and high-density lipoprotein cholesterol were 32.3 kg/m(2) , 1.7
      mmol/L, and 1.3 mmol/L, respectively. At week 12, nebivolol and placebo groups
      demonstrated a decrease of -9.4 and -5.0 mm Hg, respectively (P<.001) for DBP and
      -10.4 and -7.8 mm Hg for SBP (P=.147). The mean changes in area under the curve
      OGTT were 0.0 mg/dL (nebivolol), 6.9 mg/dL (HCTZ; P=.024 vs nebivolol), and -1.0
      mg/dL (placebo). Adverse event-related discontinuation rates were 10.3%, 6.6%,
      and 2.0%, respectively. Nebivolol, added to an ACE inhibitor or ARB, provides
      additional blood pressure reduction with little or no effect on glucose
      metabolism in hypertensive patients with prediabetes.

PMID- 23551729
TI  - Screening for severe obstructive sleep apnea syndrome in hypertensive
      outpatients.

PMID- 23551728
TI  - Screening for severe obstructive sleep apnea syndrome in hypertensive
      outpatients.
AB  - The authors attempted to validate a 2-stage strategy to screen for severe
      obstructive sleep apnea syndrome (s-OSAS) among hypertensive outpatients, with
      polysomnography (PSG) as the gold standard. Using a prospective design,
      outpatients with hypertension were recruited from medical outpatient clinics.
      Interventions included (1) assessment of clinical data; (2) home sleep testing
      (HST); and (3) 12-channnel, in-laboratory PSG. The authors developed models using
      clinical or HST data alone (single-stage models) or clinical data in tandem with
      HST (2-stage models) to predict s-OSAS. For each model, area under receiver
      operating characteristic curves (AUCs), sensitivity, specificity, negative
      likelihood ratio, and negative post-test probability (NPTP) were computed. Models
      were then rank-ordered based on AUC values and NPTP. HST used alone had limited
      accuracy (AUC=0.727, NPTP=2.9%). However, models that used clinical data in
      tandem with HST were more accurate in identifying s-OSAS, with lower NPTP: (1)
      facial morphometrics (AUC=0.816, NPTP=0.6%); (2) neck circumference (AUC=0.803,
      NPTP=1.7%); and Multivariable Apnea Prediction Score (AUC=0.799, NPTP=1.5%) where
      sensitivity, specificity, and NPTP were evaluated at optimal thresholds.
      Therefore, HST combined with clinical data can be useful in identifying s-OSAS in
      hypertensive outpatients, without incurring greater cost and patient burden
      associated with in-laboratory PSG. These models were less useful in identifying
      obstructive sleep apnea syndrome of any severity.

PMID- 23551730
TI  - Characteristics and future cardiovascular risk of patients with not-at-goal
      hypertension in general practice in France: the AVANT'AGE study.
AB  - Although many studies focus on patients with resistant hypertension, general
      practitioners (GPs) are more likely to face patients in clinical practice with
      not-at-goal hypertension, whose antihypertensive treatment needs to be modified.
      However, information regarding such patients is limited. In the present study,
      710 GPs in France each included their first 10 not-at-goal hypertensive patients,
      ie, the patients for whom they decided to modify antihypertensive treatment. The
      study population was composed of 7032 patients (58% men, mean age 62.4+/-11.5
      years). Anthropometric and biologic measurements and clinical data were
      collected, and vascular age and 10-year cardiovascular risk were estimated by
      standard formula. Of 7032 participants, cardiovascular risk factors were
      prevalent, with 15.1% current smokers, 26.1% obese, 22.8% with diabetes mellitus,
      35.1% with dyslipidemia, 12.0% with left ventricular hypertrophy, and 4.9% with
      renal insufficiency. In the subgroup (n=4697) of patients aged between 30 and 74
      years and undergoing primary cardiovascular prevention, vascular age was superior
      (13 to 28 years) when compared with chronological age in different subgroups. The
      patients' estimated 10-year cardiovascular global risk was 25.3+/-13.6%, with
      16.0+/-10.5% for coronary heart disease, 8.7+/-6.8% for myocardial infarction,
      5.8+/-4.5% for stroke, and 6.8+/-6.6% for cardiovascular mortality. Patients with
      not-at-goal hypertension in primary care bear a heavy burden of cardiovascular
      diseases.

PMID- 23551731
TI  - Serum uric acid still carries controversies about its role in endothelial
      dysfunction.

PMID- 23551732
TI  - REPLY TO: Serum uric acid still carries controversies about its role in
      endothelial dysfunction.

PMID- 23551733
TI  - C-reactive protein, fibrinogen, and incident heart failure: combination procedure
      for statistical analysis.

PMID- 23551734
TI  - C-reactive protein, fibrinogen, and incident heart failure in the Strong Heart
      Study population.

PMID- 23551735
TI  - Visit-to-visit blood pressure variation--time to re-analyze all the data from the
      Trial of Preventing Hypertension (TROPHY) study.

PMID- 23551736
TI  - Reply to Visit-to-visit blood pressure variation: time to reanalyze all the data
      from the TROPHY study.

PMID- 23551737
TI  - Public-use blood pressure machines in pharmacies for identification of undetected
      hypertension in the community.

PMID- 23551738
TI  - Arterial stiffness itself without other inflammatory markers may not provide
      information to clinicians.

PMID- 23551739
TI  - Association of arterial stiffness with obesity in Australian women: a pilot
      study.

PMID- 23551740
TI  - Classification of left ventricular diastolic function using American Society of
      Echocardiography Guidelines: agreement among echocardiographers.
AB  - Guidelines for assessing diastolic function by echocardiography are continually
      being updated. Our ability to use available guidelines effectively has not been
      completely investigated. Six trained echocardiographers were asked to interpret
      105 echocardiograms using current American Society of Echocardiography (ASE)
      algorithms for interpretation of diastolic grade and estimation of left atrial
      (LA) pressure. Diastolic grade was categorized as normal, mild, moderate, or
      severe dysfunction. The presence or absence of elevated LA pressure was
      determined using a second ASE algorithm. As a reference comparison for level of
      agreement, left ventricular ejection fraction was visually determined. By the ASE
      algorithm, 29 subjects (28%) met all measurement criteria in their assigned grade
      and 57 subjects (55%) met all or all but one criterion of their assigned grade.
      Of the 45 subjects (43%) for whom the guidelines disagreed by more than 1
      criterion, the readers debated between normal and moderate dysfunction in 22% or
      mild and moderate diastolic dysfunction in 31%. Percent inter-reader agreement
      and kappa values were 76% (0.7) for determining diastolic grade, 84% (0.67) for
      determining elevated LA pressure, and 84% (0.67) for estimation of ejection
      fraction, the reference standard. For all subjects, if multiple echocardiographic
      criteria failed to fit into the proposed guidelines, agreement fell to 66% (0.58)
      for determining diastolic grade and 74% (0.48) for determining LA pressure. There
      is reasonable agreement estimating diastolic grade and LA pressure using current
      guidelines. Further refinements in the definition of mild and moderate
      dysfunction may improve agreement. 

PMID- 23551741
TI  - Variation of motivation between weekday and weekend donors and their association
      with distance from blood donation centres.
AB  - BACKGROUND: Maintenance of an effective pool of regular donors is important for
      protecting public health. In planning the development of blood donation services,
      motivation for repeat donation would need to be considered in context of the
      location of blood donation centres in the community. STUDY DESIGN AND METHODS:
      Donors giving blood in January 2012 were invited to participate in a cross
      sectional study by completing an anonymous online questionnaire. Residence and
      work/school locations were collected together with demographics and donation
      histories. Motivated donors were compared with less motivated ones in terms of
      their timing of blood donation and the spatial relationship with the donor
      centres. RESULTS: A total of 3744 questionnaires were completed, representing a
      response rate of 16.4%. Weekday centre donors were less likely to have returned
      for blood donation within a year [odds ratio (OR) = 0.79, 95% confidence interval
      (CI) = 0.65-0.96] and intend to donate in the following 6 months (OR = 0.69, 95%
      CI = 0.49-0.97). Living further away from the donor centres gave a higher OR for
      giving blood during weekdays among motivated centre donors, but such association
      was absent among less motivated centre donors. Regardless of the level of donors'
      motivation for blood donation, fewer weekday donations were made if the distance
      between location of school or workplace and donor centre increased. CONCLUSION:
      Blood donation behaviour was associated with both the accessibility of donor
      centres and daily commuting patterns of the residents. Motivated centre donors
      were making more donations, regardless of the distance.

PMID- 23551742
TI  - Tunneled melolabial pedicle flap for small but deep lateral alar rim defect.

PMID- 23551743
TI  - Therapy or threat? Inadvertent exposure to alcohol and illicit drug cues in the
      neighbourhoods of sober living homes.
AB  - Alcohol retail outlets and other environmental cues can contribute to relapse
      among individuals recovering from substance abuse. Sober living homes are
      residences designed to strengthen abstinence from substances, in part by helping
      residents develop skills for coping with cues and other stressors. Between
      January 2009 and March 2010, we conducted 10 focus groups with 68 adults aged 18
      and over who lived in or operated any of 35 sober living homes in Los Angeles
      County, California. A stratified purposive sampling strategy was used to recruit
      sober living home residents and operators. The study aim was to assess how
      residents responded to the neighbourhood alcohol and drug cues they encountered
      in their daily lives. The focus group transcripts were analysed using the
      constructs of 'approach coping' and 'avoidance coping'. Findings suggest that the
      sober living homes helped residents cope with cue exposure through social rules
      and processes such as chaperones and evening curfews, as well as the presence of
      peer support for managing the conflictive thoughts and emotions that result from
      cue exposure. The examples of 'avoidance coping' and 'approach coping' identified
      in the transcripts were more often behavioural than cognitive. For example,
      residents described efforts they made to increase their physical distance from
      (i.e. avoid) neighbours who used substances. Whereas some participants believed
      that living in areas with high levels of drug use and trafficking was 'a time
      bomb' for relapse, others suggested that cue exposure could actually strengthen
      their ability to remain abstinent ('approach coping'). The approach/avoidance
      coping construct did not account for the experiences of all residents. Several
      participants expressed indifference towards cues while performing daily routines
      and pursuing important recovery goals. The threat of alcohol and drug cues may be
      mitigated by recovery-oriented homes that support coping on an individualised, as
      needed basis. 

PMID- 23551744
TI  - Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with
      and without PRRT2 mutations.
AB  - BACKGROUND AND PURPOSE: Mutations in the PRRT2 gene have been identified in
      patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many
      detailed clinico-genetic correlations have been performed. METHODS: To
      investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico
      genetic correlations, we recruited patients between 2002 and 2011 and
      administered a standardized questionnaire. RESULTS: Amongst 29 unrelated patients
      with PKD recruited, five PRRT2 mutations were present in 15 patients. Three
      mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three
      were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs;
      c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a
      history of seizures was more common in patients with PRRT2 mutations, although
      this did not reach statistical significance (P= 0.08). A younger age of onset,
      non-Chinese, and the presence of premonitory sensations were significantly
      associated with PRRT2 mutations in the univariate analysis. Multivariate logistic
      regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, P =
      0.025] and premonitory sensation (OR = 10.67, P = 0.028) were independently
      associated with positive PRRT2 mutation. CONCLUSIONS: PRRT2 mutations are common
      in patients with PKD, and a double PRRT2 mutation is reported for the first time.
      PRRT2 mutations are significantly associated with a younger age of onset and the
      presence of premonitory sensation in our population.

PMID- 23551745
TI  - Assessing the use of haemostatic sealants in tubeless percutaneous renal access
      and their effect on renal drainage and histology: an experimental porcine study.
AB  - OBJECTIVE: To evaluate the mid-term effects of haemostatic sealant application
      during tubeless percutaneous nephrolithotomy (PCNL) on renal drainage and
      histology in an in vivo porcine study. MATERIALS AND METHODS: Bilateral
      percutaneous access was established in 28 porcine renal units. At the end of the
      procedure, a type 1 absorbable fish origin collagen powder, a human fibrinogen-
      and thrombin-coated sponge or a cross-linked gelatin granule/topical thrombin
      matrix were randomly placed on the nephrostomy tracts. Four nephrostomy accesses
      were left intact and served as controls. No percutaneous tube, ureteric stent or
      bladder catheter was left in place postoperatively. Computed tomography urography
      on postoperative days 1, 15, 30 and 40 was used to access renal drainage. On
      postoperative day 40, all animals were killed and both kidneys from each animal
      were harvested for histological evaluation. RESULTS: Evidence of risk for
      drainage occlusion after sealant application was found. The use of haemostatic
      sealants was associated with significant histological lesions in the renal
      parenchyma, regardless of which sealant was used. No sealant was identified as
      superior to the others. Nephrostomy tracts that were left without sealant
      application (control group) were associated with no morbidity and fewer
      histopathological changes. CONCLUSIONS: Based on these experimental results, the
      safety of the application of haemostatic sealants in tubeless PCNL should be
      reassessed, focusing not only on the potential of such materials to occlude
      urinary drainage but also on their effect on renal histology. Further
      investigation is considered necessary.

PMID- 23551746
TI  - Gastrointestinal hemodynamics in dogs with nonfood induced atopic dermatitis.
AB  - BACKGROUND: Canine atopic dermatitis can be a result of exposure to aeroallergens
      or trophallergens. Hemodynamic alterations occur in dogs with food
      hypersensitivity. HYPOTHESIS/OBJECTIVES: To evaluate if hemodynamic alterations
      occur in dogs with NFICAD with lowered resistance to diastolic flow at fasting,
      after feeding, or both. ANIMALS: Ten healthy dogs and 22 dogs with NFICAD were
      included from the hospital population. METHODS: Blinded prospective study. Peak
      systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV),
      pulsatility index (PI), resistive index (RI) and PSV/EDV ratio were measured at
      fasting for both arteries (cranial mesenteric artery [CMA], celiac artery [CA])
      and at 40 minutes after feeding in CMA and at 60 minutes in CA. The results were
      analyzed statistically with a mixed model. RESULTS: There was no difference
      detected between groups of dogs for any variable except EDV during fasting (P =
      .01). CONCLUSIONS AND CLINICAL IMPORTANCE: There is no decrease in resistance in
      NFICAD to diastolic flow. This observation could be explained by the absence
      intestinal inflammation in NFICAD.

PMID- 23551747
TI  - Recycling of pyridoxine (vitamin B6) by PUP1 in Arabidopsis.
AB  - Vitamin B6 is a cofactor for more than 140 essential enzymatic reactions and was
      recently proposed as a potent antioxidant, playing a role in the photoprotection
      of plants. De novo biosynthesis of the vitamin has been described relatively
      recently and is derived from simple sugar precursors as well as glutamine. In
      addition, the vitamin can be taken up from exogenous sources in a broad range of
      organisms, including plants. However, specific transporters have been identified
      only in yeast. Here we assess the ability of the family of Arabidopsis purine
      permeases (PUPs) to transport vitamin B6. Several members of the family
      complement the growth phenotype of a Saccharomyces cerevisiae mutant strain
      impaired in both de novo biosynthesis of vitamin B6 as well as its uptake. The
      strongest activity was observed with PUP1 and was confirmed by direct measurement
      of uptake in yeast as well as in planta, defining PUP1 as a high affinity
      transporter for pyridoxine. At the tissue level the protein is localised to
      hydathodes and here we use confocal microscopy to illustrate that at the cellular
      level it is targeted to the plasma membrane. Interestingly, we observe
      alterations in pyridoxine recycling from the guttation sap upon overexpression of
      PUP1 and in a pup1 mutant, consistent with the role of the protein in retrieval
      of pyridoxine. Furthermore, combining the pup1 mutant with a vitamin B6 de novo
      biosynthesis mutant (pdx1.3) corroborates that PUP1 is involved in the uptake of
      the vitamin.

PMID- 23551748
TI  - Current role of short-term intensive insulin strategies in newly diagnosed type 2
      diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by
      worsening insulin resistance and a decline in beta-cell function. Achieving good
      glycemic control becomes more challenging as beta-cell function continues to
      deteriorate throughout the disease process. The traditional management paradigm
      emphasizes a stepwise approach, and insulin has generally been reserved as a
      final armament. However, mounting evidence indicates that short-term intensive
      insulin therapy used in the early stages of type 2 diabetes could improve beta
      cell function, resulting in better glucose control and more extended glycemic
      remission than oral antidiabetic agents. Improvements in insulin sensitivity and
      lipid profile were also seen after the early initiation of short-term intensive
      insulin therapy. Thus, administering short-term intensive insulin therapy to
      patients with newly diagnosed T2DM has the potential to delay the natural process
      of this disease, and should be considered when clinicians initiate treatment.
      Although the early use of insulin is advocated by some guidelines, the optimal
      time to initiate insulin therapy is not clearly defined or easily recognized, and
      a pragmatic approach is lacking. Herein we summarize the current understanding of
      early intensive insulin therapy in patients with newly diagnosed T2DM, focusing
      on its clinical benefit and problems, as well as possible biological mechanisms
      of action, and discuss our perspective. 

PMID- 23551749
TI  - Evaluation of an education and follow-up programme for implantable cardioverter
      defibrillator-implanted patients.
AB  - AIMS AND OBJECTIVES: To determine the experiences, problems and the need for care
      and education of implantable cardioverter defibrillator-implanted patients and to
      assess the effects of an education and nurse follow-up programme on their quality
      of life, anxiety, depression and knowledge level. BACKGROUND: Although
      implantable cardioverter defibrillator has become a well-established therapy for
      people experiencing potentially lethal dysrhythmias, implantable cardioverter
      defibrillator patients may have physical and psychosocial problems due to the
      implantation. Applying a planning education and follow-up programme to
      implantable cardioverter defibrillator-implanted patients may prevent the need
      for more intensive treatment during the postimplantation period. DESIGN: A mixed
      methods design that used both qualitative and quantitative data collections and
      analysis was used for this study. METHODS: The study was performed in the
      cardiology department in Turkey between 2009-2010. The data were collected using
      the 'Semi-Structured Interview Form', 'Form for Assessment of Patients' Knowledge
      Level about implantable cardioverter defibrillator', 'Spielberger's State-Trait
      Anxiety Inventory', 'Beck Depression Inventory II' and 'The Short-Form 36 Health
      Survey'. All forms were completed at the beginning of the study and at six
      months. The study included 27 patients in the experimental group and 27 patients
      in the control group. RESULTS: The results showed that the patients were living
      with various physical and psychosocial problems and insufficient knowledge
      regarding the implantable cardioverter defibrillator. Education and follow-up
      programme increased knowledge levels, decreased anxiety and depression scores and
      improved several subscales of quality of life in the experimental group patients.
      CONCLUSION: It was recommended that education and follow-up programme be used for
      patients scheduled to undergo implantable cardioverter defibrillator
      implantation, starting before implantation and continuing thereafter, to help
      patients adapt to a life with implantable cardioverter defibrillator. RELEVANCE
      TO CLINICAL PRACTICE: Planned education and follow-up programme conducted by
      nurses may improve the knowledge levels and quality of life, anxiety and
      depression scores of the implantable cardioverter defibrillator-implanted
      patients.

PMID- 23551750
TI  - Orthodontic treatment and implant-prosthetic rehabilitation of a partially
      edentulous patient.
AB  - This article describes the treatment of a 61-year-old man who had a completely
      edentulous maxillary arch and partially edentulous mandibular arch. The patient
      was orthodontically treated to correct an anterior crossbite by distalization of
      the mandibular teeth using a removable prosthesis serving as an anchorage unit.
      Subsequently, the patient received two zygomatic implants, five conventional
      implants in the maxillary arch, and six conventional implants in the mandibular
      arch. By the end of treatment, the convexity of the facial profile improved, and
      esthetic and functional occlusion was established. 

PMID- 23551751
TI  - MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in
      glioma.
AB  - AIMS: Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in
      human glioblastoma, conferring a survival advantage to tumor cells. The
      mechanisms underlying its dysregulation have not been clarified. In this study,
      we explored the involvement of micro-RNAs that acted as endogenous sequence
      specific suppressors of gene expression. METHODS AND RESULTS: Using computational
      and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma
      in comparison with human brain tissue, as well as possessing a putative target
      site in Mcl-1 mRNA. Overexpression of miR-139 led to a clear decrease in Mcl-1
      expression in gliomas. Reporter assays revealed direct post-transcriptional
      regulation involving miR-139 and the 3'-untranslated region of Mcl-1. Human
      glioma tissues with low expression of miR-139 displayed higher expression of Mcl
      1 protein than those with high expression, suggesting that low miR-139
      contributes to Mcl-1 overexpression. In addition, upregulation of miR-139
      suppressed the proliferation and enhanced temozolomide (TMZ)-induced apoptosis.
      Finally, we observed that Mcl-1 knockdown resulted in similar effects compared
      with miR-139 transfection. CONCLUSION: Our results suggested that miR-139
      negatively regulated Mcl-1 and induced apoptosis in cooperation with an
      anticancer drug TMZ in glioma.

PMID- 23551753
TI  - Women with deep infiltrating endometriosis: sexual satisfaction, desire, orgasm,
      and pelvic problem interference with sex.
AB  - INTRODUCTION: Endometriosis is a chronic and progressive condition of women of
      reproductive age. It is strongly associated with a significant reduction of
      quality of life (QOL) and sexual function. AIMS: This study aims to objectively
      evaluate sexual function in women with deep infiltrating endometriosis (DIE) and
      to study the impact of endometriosis symptoms and type of lesion on patient's
      sexual function. METHODS: This is a cross-sectional study in a tertiary care
      university hospital. It included 182 patients with preoperative clinical and
      ultrasound diagnosis of DIE who were referred to our center from 2008 to 2011.
      MAIN OUTCOME MEASURES: A sexual activity questionnaire, the Sexual Health
      Outcomes in Women Questionnaire (SHOW-Q) was used to collect data pertaining to
      satisfaction, orgasm, desire, and pelvic problem interference with sex. Short
      Form 36 (SF-36) was used to evaluate QOL. Demographic and clinical
      characteristics were assessed: age, body mass index, parity, ethnicity,
      postsecondary education, employment, smoking, history of surgical treatment, and
      hormonal contraception. Patients were asked about pain symptoms (dysmenorrhea,
      dyspareunia, dyschezia, chronic pelvic pain, and dysuria) using a visual analog
      scale. RESULTS: The mean values obtained on the different scales of the SHOW-Q
      showed poor sexual function (mean SHOW-Q total score 56.38 +/- 22.74).
      Satisfaction was the dimension most affected (mean satisfaction score 55.66 +/-
      34.55), followed by orgasm (mean orgasm score 56.90 +/- 33.77). We found a
      significant correlation between the SF-36 scores and the SHOW-Q scores (P <
      0.0001). Sexual dysfunction and deterioration of QOL seem to be correlated.
      Analyzing the impact of symptoms and lesions on sexual function, we found that
      dyspareunia and vaginal DIE nodules significantly affect sexual activity (P <
      0.05). CONCLUSION: The results of this study demonstrated that women with DIE
      have a sexual function impairment, correlated with the overall well-being
      decrease. Moreover, the presence of dyspareunia and vaginal endometriotic lesions
      seems to be involved in sexual dysfunction.

PMID- 23551754
TI  - Post-esophagectomy gastric conduit cancers: treatment experiences and literature
      review.
AB  - Esophagectomy remains the mainstay of treatment for esophageal cancer. The
      stomach is the commonest organ used to restore intestinal continuity after
      esophagectomy. Metachronous gastric cancer in the gastric conduit after
      esophagectomy is rare; the etiology remains unclear. Possible risk factors
      include Helicobacter pylori infection, biliary or pancreatic reflux and prior
      radiotherapy. Prognosis of these patients remains poor. Treatment of this
      particular entity poses unique challenges to the surgeon and oncologist. Early
      diagnosis by endoscopy may allow endoscopic excision such as endoscopic mucosal
      resection or endoscopic submucosal dissection. In more advanced cancers, surgery
      is difficult, reconstruction is complicated, and further radiation may not be
      feasible because of previous neoadjuvant therapy. In this report, four patients
      who developed gastric conduit cancers are presented. They were treated with
      either surgery alone or combined with chemoradiotherapy. All four patients were
      still alive after at least 21 months, with three patients currently still alive
      (21-48 months). The literature is also reviewed, in particular addressing the
      incidence, possible underlying causes, prognosis and options of treatment for
      this specific clinical scenario. 

PMID- 23551757
TI  - Differences in the effect of maternal smoking during pregnancy for childhood
      overweight before and after 5 years of age.
AB  - AIM: This study aimed to clarify the association between maternal smoking during
      pregnancy and childhood overweight during different periods using two cohort
      studies from the same population: the birth cohort (the 1st cohort) and the non
      overweight children at 5 years of age cohort (the 2nd cohort) by sex. MATERIAL
      AND METHODS: The study population comprised children born between 1 April 1991
      and 31 March 1999 in Koshu City, Yamanashi Prefecture, Japan, and their mothers.
      The dependent variables were diagnosis of overweight in each cohort. The primary
      independent variable was maternal smoking during pregnancy. Multiple logistic
      regression models were applied for these statistical analyses. RESULTS: Mothers
      who answered the questionnaire during early pregnancy gave birth to a total of
      1644 babies during the study period. The 1st cohort consisted of these babies and
      were followed until 5 years of age. The 2nd cohort consisted of 1131 children who
      were diagnosed as normal weight at 5 years of age and followed until 9-10 years
      of age. There was an association between maternal smoking during pregnancy and
      overweight only in boys in the 1st cohort analysis (adjusted odds ratio, 4.5; 95%
      confidence interval, 2.0-10.2). CONCLUSIONS: These results suggest that the
      effects of maternal smoking during pregnancy on childhood overweight tend to
      appear before 5 years of age, especially in boys. It is necessary for children
      whose mother smoked during pregnancy, especially in boys, to be careful with
      their diet and physical activity in order to prevent childhood obesity.

PMID- 23551755
TI  - Mood lability among offspring of parents with bipolar disorder and community
      controls.
AB  - OBJECTIVES: Early identification of bipolar disorder (BP) symptomatology is
      crucial for improving the prognosis of this illness. Increased mood lability has
      been reported in BP. However, mood lability is ubiquitous across psychiatric
      disorders and may be a marker of severe psychopathology and not specific to BP.
      To clarify this issue, this study examined the prevalence of mood lability and
      its components in offspring of BP parents and offspring of community control
      parents recruited through the Pittsburgh Bipolar Offspring Study. METHODS: Forty
      one school-age BP offspring of 38 BP parents, 257 healthy or non-BP offspring of
      174 BP parents, and 192 offspring of 117 control parents completed a scale that
      was developed to evaluate mood lability in youth, i.e., the Children's Affective
      Lability Scale (CALS). RESULTS: A factor analysis of the parental CALS, and in
      part the child CALS, revealed Irritability, Mania, and Anxiety/Depression
      factors, with most of the variance explained by the Irritability factor. After
      adjusting for confounding factors (e.g., parental and offspring non-BP
      psychopathology), BP offspring of BP parents showed the highest parental and
      child total and factor scores, followed by the non-BP offspring of BP parents,
      and then the offspring of the controls. CONCLUSIONS: Mood lability overall and
      mania-like, anxious/depressed, and particularly irritability symptoms may be a
      prodromal phenotype of BP among offspring of parents with BP. Prospective studies
      are warranted to clarify whether these symptoms will predict the development of
      BP and/or other psychopathology. If confirmed, these symptoms may become a target
      of treatment and biological studies before BP develops.

PMID- 23551758
TI  - Stretch-shortening cycle muscle power in women and men aged 18-81 years:
      Influence of age and gender.
AB  - This study explored the age-related deterioration in stretch-shortening cycle
      (SSC) muscle power and concurrent force-velocity properties in women and men
      across the adult life span. A total of 315 participants (women: n = 188; men: n =
      127) aged 18-81 years performed maximal countermovement jumps on an instrumented
      force plate. Maximal SSC leg extension power expressed per kg body mass (Ppeak)
      was greater in men than in women across the adult age span (P < 0.001); however,
      this gender difference was progressively reduced with increasing age, because men
      showed an ~50% faster rate of decline in SSC power than women (P < 0.001).
      Velocity at peak power (VPpeak) was greater in men than in women (P < 0.001) but
      declined at a greater rate in men than in women (P = 0.002). Vertical ground
      reaction force at peak power (FPpeak) was higher in men than in women in younger
      adults only (P < 0.001) and the age-related decline was steeper in men than in
      women (P < 0.001). Men demonstrated a steeper rate of decline in Ppeak than women
      with progressive aging. This novel finding emerged as a result of greater age
      related losses in men for both force and velocity. Consequently, maximal SSC
      power production was observed to converge between genders when approaching old
      age.

PMID- 23551759
TI  - Robot-assisted laparoscopic artificial urinary sphincter insertion in men with
      neurogenic stress urinary incontinence.
AB  - OBJECTIVE: To describe for the first time the technique of robot-assisted
      artificial urinary sphincter (R-AUS) insertion in male patients with neurogenic
      incontinence. MATERIALS AND METHODS: From January 2011 to the present date, six
      patients with spinal cord injury have undergone R-AUS insertion at our academic
      institution and we have prospectively collected data on pre-, peri- and early
      postoperative outcomes. A transperitoneal five-port approach was used using a
      three-arm standard da Vinci(r) robot (Intuitive Surgical, Sunnyvale, CA, USA) in
      a 30 degrees  reverse Trendelenburg position. The artificial urinary sphincter
      (AUS) cuff was placed circumferentially around the bladder neck, the reservoir
      was left intra-abdominally in a lateral vesicular space and the pump was placed
      in a classic scrotal position. RESULTS: All six patients had successful robotic
      implantation of the AUS. The median patient age was 51.5 years, the median
      (range) operating time was 195 (175-250) min with no significant blood loss or
      intra-operative complications. The median (range) length of hospital stay was 4
      (4-6) days. At a median (interquartile range) follow-up of 13 (6-21) months, all
      six patients had a functioning device with complete continence. To date, we have
      observed no incidence of early erosion, device infection or device malfunction.
      CONCLUSIONS: Allowing for the preliminary nature of our data, R-AUS insertion
      appears safe and technically feasible. Larger studies with long-term follow-up
      and comparison with open AUS insertion are necessary before definitive statements
      can be made for R-AUS in respect of complications and functional outcomes.

PMID- 23551760
TI  - Sex differences in cerebral palsy incidence and functional ability: a total
      population study.
AB  - AIM: To describe gender difference in a total population of children with
      cerebral palsy (CP), related to subtype, gross and fine motor function, and to
      compare CP incidence trends in girls and boys. METHODS: All 590 children with CP
      born in southern Sweden 1990-2005 were included. CP subtype was classified
      according to the Surveillance of Cerebral Palsy in Europe, gross motor function
      according to Gross Motor Function Classification System (GMFCS) and manual
      ability according to Manual Ability Classification System (MACS). Trends in CP
      incidence by birth year were analysed using Poisson regression modelling.
      RESULTS: There was a male predominance in all levels of GMFCS except level II, in
      all levels of MACS and in all CP subtypes except ataxic CP. There was no
      statistically significant difference between males and females regarding gross
      motor function or manual ability. The CP incidence trends in boys compared with
      girls did not change during the period 1990-2005. CONCLUSION: No equalization was
      detected in the incidence of CP between girls and boys during recent years in
      this total population. We could not confirm any consistent sex difference in
      motor function levels. Male sex is a risk factor for CP.

PMID- 23551761
TI  - Triangular rotation flap for repair of partial earlobe deformity.

PMID- 23551762
TI  - Increased neuronal firing in resting and sleep in areas of the macaque medial
      prefrontal cortex.
AB  - The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of
      the default mode network and is a brain region that shows increased activation in
      the resting state. A previous paper from our laboratory reported significantly
      increased firing rates of neurons in the macaque subgenual cingulate cortex,
      Brodmann area (BA) 25, during disengagement from a task and also during slow wave
      sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report
      the finding that there are neurons in other areas of mPFC that also increase
      their firing rates during disengagement from a task, drowsiness and eye-closure.
      During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9,
      10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were
      identified whose firing rates altered significantly with eye-closure compared
      with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of
      the total population) significantly increased (mean + 329%; P ? 0.01) their
      average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2
      spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P <
      0.05) their firing rate on eye-closure; and Type 3 cells (65.9%) were unaffected.
      Thus, in many areas of mPFC, implicated in the anterior default mode network,
      there is a substantial population of neurons that significantly increase their
      firing rates during periods of eye-closure. Such neurons may be part of an
      interconnected network of distributed brain regions that are more active during
      periods of relaxed wakefulness than during attention-demanding tasks.

PMID- 23551763
TI  - Headline: a year in review: thank you for being part of the academy's success.

PMID- 23551764
TI  - Assessing salivary osmolality as a caries risk indicator in cerebral palsy
      children.
AB  - BACKGROUND: Salivary osmolality reflects the hydration status of individuals with
      cerebral palsy (CP) necessary for an adequate unstimulated salivary flow rate.
      AIM: To investigate whether salivary osmolality could serve as a potential
      indicator of caries risk in children with spastic CP by displaying a stronger
      association with caries occurrence than salivary flow rate. DESIGN: The
      convenience sample consisted of 65 children with CP aged 6-13 years old.
      Unstimulated whole saliva was collected using cotton roll, and salivary
      osmolality was measured using a freezing point depression osmometer. The
      children's oral motor performance was evaluated during the feeding process using
      the Oral Motor Assessment Scale. Caries occurrence was also evaluated according
      the World Health Organization criteria. RESULTS: Motor skills were significantly
      associated with caries experience. Regarding the salivary parameters, osmolality
      presented a stronger association with caries experience than did the salivary
      flow rate. Children with worse oral motor performance presented a higher rate of
      caries occurrence. CONCLUSION: Osmolality exhibited a stronger association with
      caries occurrence than did salivary flow rate. This parameter, therefore, could
      be a potential caries risk indicator for spastic cerebral palsy children.

PMID- 23551765
TI  - Refractory Henoch-Schonlein purpura: atypical aetiology and management.
AB  - BACKGROUND: A 27-year-old white male was referred with recently diagnosed
      refractory Henoch-Schonlein purpura nephritis (HSPN). He had a past medical
      history of hypertension of four years duration and was prescribed lisinopril. He
      was switched from a brand to a generic lisinopril two days before the onset of
      first symptoms. On two occasions symptoms had worsened while trying to switch
      back to the generic drug. He had 9 g/day protein in his urine with haematuria and
      serum creatinine was up to 123.76 umol/l (normal value < 106 umol/l). TREATMENT:
      The patient underwent two renal biopsies; the first was carried out early after
      having HSP symptoms and the second was performed a month later. The first biopsy
      showed mild segmental endocapillary hypercellularity with IgA deposits consistent
      with HSPN. The second biopsy showed proliferative IgA nephropathy with focal
      active cellular crescent formation in 38% of the glomeruli. RESULTS: He did not
      respond to steroids, cyclophosphamide and plamapheresis. However, his renal and
      extra-renal manifestations eventually improved after he had received three doses
      of 1,000 mg rituximab by infusion, two weeks apart. CONCLUSION: Rituximab might
      be efficacious in treatment of hspn, more studies are needed to assess long-term
      safetey and efficacy.

PMID- 23551766
TI  - Subjective experiences of compulsory treatment from a qualitative study of early
      implementation of the Mental Health (Care & Treatment) (Scotland) Act 2003.
AB  - Compulsory psychiatric treatment is highly contested, and little research has
      focused specifically on direct experiences. The Mental Health (Care & Treatment)
      (Scotland) Act, 2003 introduced new roles and provisions including community
      treatment orders, and was designed to increase participation, ensure treatment
      was beneficial and was the 'least restrictive' alternative. This article draws on
      findings from semi-structured interviews with 49 individuals, who had experienced
      compulsion under this new legislation during 2007-2008, that were part of a
      broader cohort study. Interviews with service users were conducted at two stages
      with 80% agreeing to be interviewed twice. The sample included people on a
      variety of compulsory orders from four Health Board areas, some of whom had been
      detained for the first time, while others reported 'revolving door' experiences.
      Peer researchers who were mental health service users carried out the interviews
      in partnership with professional researchers. The findings suggest that
      legislation had a limited impact on participation in the process of compulsion.
      Consensus was that although service users felt there was increased opportunity
      for their voices to be heard, this was not matched by having increased influence
      over professional decision-making, especially in relation to drug treatments.
      According to people's direct experiences, the passing of the legislation in
      itself had done little to change the dominant psychiatric paradigm. While
      providing a foundation for improving the process of compulsion, the findings
      suggest that as well as legislative reform, fundamental shifts in practice are
      needed both in terms of the nature of therapeutic relationships, and in embracing
      more holistic and recovery perspectives. 

PMID- 23551767
TI  - Back to baseline: erectile function recovery after radical prostatectomy from the
      patients' perspective.
AB  - INTRODUCTION: A variety of erectile function recovery (EFR) rates are reported
      post-radical prostatectomy (RP), with some suggesting EFR rates over 90% [1].
      Clinical experience suggests that patients view EFR as getting back to their
      baseline (BTB) erectile functioning (EF) without the use of medication. AIM: This
      study explores EFR defined as BTB. METHOD: Men pre-RP and 24 months post-RP
      completed the Erectile Function Domain (EFD) of the International Index of
      Erectile Function and one question on phosphodiesterase type 5 inhibitor (PDE5i)
      use. Men using a PDE5i at baseline were excluded. MAIN OUTCOME MEASURES: At 24 m,
      "back to baseline" was defined as achieving the baseline EFD score (within 1
      point or higher). Analyses included descriptive statistics, chi-square, and
      logistic regression. RESULTS: One hundred eighty men had an average age at RP of
      59 (SD = 7) years. When including men who were using a PDE5i at 24 months, 43% (N
      = 78, 95% CI: 36-51%) returned BTB. When considering BTB without the use of a
      PDE5i, 22% (N = 39, 95% CI: 16% to 28%) returned BTB. When focusing on a subset
      of men with baseline EFD >= 24 (N = 132), 36% (N = 47, 95% CI: 28% to 44%)
      returned BTB at 24 months using a PDE5i and 16% (N = 21, 95% CI: 11% to 23%)
      without the use of a PDE5i. For this group, there was a significant difference by
      age (<60 years, 23% vs. >= 60 years, 4%, P < 0.001), which remained a significant
      predictor (OR = 6.25, 95% CI: 1.88 to 50, P < 0.001) in multivariable analysis.
      CONCLUSIONS: Twenty-two percent of the entire sample and 16% of the men with
      functional (EFD >= 24) baseline erections returned to BTB EF without the use of
      medication. Only 4% of men who were >= 60 years old with functional erections pre
      surgery achieved BTB EF. Although gaining partial EF is also important, men pre
      RP should be educated on EFR and the chance of "back to baseline" EF.

PMID- 23551769
TI  - Contrast-enhanced magnetic resonance angiography of the peripheral arteries:
      technique, tips, pitfalls and problems.
AB  - Contrast-enhanced magnetic resonance angiography is a reliable way to assess
      peripheral vascular disease. This article reviews the basic physics behind this
      technique and discusses our institution's experience with regard to the clinical
      role, recent advances in image acquisition and use of contrast agents. Problems
      that can affect image quality and interpretation are also highlighted.

PMID- 23551770
TI  - Dynamic volumetric computed tomographic assessment of the young paediatric
      airway: Initial experience of rapid, non-invasive, four-dimensional technique.
AB  - INTRODUCTION: The aim of this study was to evaluate the dynamic volumetric CT in
      the assessment of the paediatric airway. METHODS: Ethics board approval was
      obtained for this retrospective review. Eight infants (median age 6 months, range
      3 weeks to 1 year, 50% female) at a tertiary paediatric centre with complex
      clinical respiratory presentation underwent volumetric CT assessment of their
      airways. The entire lungs were examined over 1-2 respiratory cycles. In four
      patients, intravenous contrast was administered to assess for vascular airway
      compression. The patients were not intubated. CT findings were correlated with
      bronchography and bronchoscopy, where available. RESULTS: Two patients had
      diffuse tracheobronchomalacia associated with chronic lung disease. One patient
      demonstrated focal severe cervical tracheomalacia. One patient had a double
      aortic arch causing fixed narrowing with superimposed malacia of the distal
      trachea. Four patients had normal airways; one with chronic lung disease, one
      demonstrating air trapping. CT findings were concordant with bronchography (one
      case) and bronchoscopy (four cases) in all but one (CT negative, bronchoscopy
      positive) but did not alter patient management. CONCLUSION: The assessment of the
      paediatric airway, and in particular for tracheobronchomalacia, is difficult.
      Assessment with bronchography, bronchoscopy, helical CT and MR have issues with
      reliability, intubation, intratracheal/bronchial contrast administration and
      ionising radiation. Volumetric CT assesses the entire central airway in children
      at much lower radiation dose compared with previous dynamic CT imaging. This non
      invasive, rapid assessment obviates the need for patient cooperation and enables
      evaluation of extratracheal intrathoracic structures. Volumetric CT enables four
      dimensional assessment for paediatric tracheobronchomalacia without intubation or
      patient cooperation and at low radiation dose.

PMID- 23551771
TI  - Mechanical thrombectomy with the Solitaire AB device in large intracerebral
      artery occlusions.
AB  - INTRODUCTION: Mechanical thrombectomy has the potential to revolutionise the
      treatment of acute stroke. The Solitaire AB device is used for clot retrieval
      with unprecedented revascularisation rates being reported. Our aim is to report
      our experiences of the safety and efficacy of the Solitaire AB device in acute
      ischaemic stroke. METHODS: A retrospective dual-centre study of 21 patients with
      acute ischaemic stroke who underwent mechanical thrombectomy with the Solitaire
      AB device between 1 October 2010 and 1 December 2011 was carried out. Using
      clinical data recovered from patients' case notes, we identified time intervals
      from groin puncture to recanalisation, revascularisation rates, procedural
      complications and neurological status before and after treatment (using the
      National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale
      (mRS) respectively). RESULTS: Successful revascularisation, defined as Thrombosis
      in Cerebral Ischemia Grade 2 or 3, was achieved in 81% of cases. The mean NIHSS
      score at presentation was 18.5. The mean number of passes required to achieve
      recanalisation was 1.95 and the median duration of the procedure from groin
      puncture to recanalisation was 65 min. Procedural events included distal emboli
      (n = 2), arterial dissection (n = 1) and arterial perforation (n = 1).There were
      three cases of asymptomatic intracranial haemorrhage. Forty-eight per cent of
      patients achieved a good functional outcome at 3 months (mRS score <=2). The
      mortality rate at 3 months was 19% (n = 4). There was no procedure-related
      mortality. CONCLUSIONS: Mechanical thrombectomy with the Solitaire AB device is
      safe and achieves high rates of revascularisation in acute stroke with good
      clinical outcomes.

PMID- 23551772
TI  - Dual source CT angiography in popliteal artery entrapment syndrome.
AB  - AIM: To evaluate the clinical value of dual source computed tomography (DSCT)
      angiography in the diagnosis and treatment for popliteal artery entrapment
      syndrome (PAES). MATERIALS AND METHODS: 8 patients with PAES were retrospectively
      reviewed. 64-slice dual source CT angiography was performed based on the
      following protocol: 100 mL of Iopamidol (370 mgI/mL) was injected at a rate of
      3.5 mL/s and arterial phase images were obtained by using bolus tracking. Axial
      DSCT images and reconstructed images including multi-planar reconstruction (MPR),
      maximum intensity projection (MIP), volume rendering (VR) were collected and
      analysed. All patients underwent Doppler colour ultrasound examinations and
      surgeries. RESULTS: The popliteal artery and the neighbouring muscular structures
      were clearly shown on the axial images revealing the cause of the arterial
      entrapment. Furthermore, the site and length of the segmental occlusion and
      collateral developments were well demonstrated on reconstructed images.
      Characterisation and classification based on DSCT angiography were confirmed by
      surgeries. PAES was accurately diagnosed by DSCT angiography in all enrolled
      patients. In contrary, only 5 PAES cases were accurately diagnosed by ultrasound
      examination. CONCLUSION: DSCT angiography is a noninvasive and valuable tool in
      the diagnosis of PAES and plays an important role in the determination of
      treatment plans.

PMID- 23551773
TI  - Head injury: audit of a clinical guideline to justify head CT.
AB  - INTRODUCTION: Head injury causes significant morbidity and mortality, and there
      is contention about which patients to scan. The UK National Health Service
      Clinical Guideline (CG) 56 provides criteria for selecting patients with
      clinically important brain injury who may benefit from a head CT scan, while
      minimising the radiation and economic burden of scanning patients without
      significant injury. This study aims to audit the documentation of the use of
      these guidelines in a busy UK trauma hospital and discusses the comparison with
      an Australian (New South Wales (NSW) ) head injury guideline. METHODS: A
      retrospective cohort study of 480 patients presenting with head injury to the
      emergency department over 2 months was performed. The patient notes were assessed
      for documentation of each aspect of the clinical guidelines. Criteria were
      established to assess the utilisation of the CG 56. A database of clinical data
      was amalgamated with the head CT scan results for each patient. RESULTS: For the
      UK CG 56, 73% of the criteria were documented, with the least documented being
      'signs of basal skull fracture' and 'amnesia of events'. Thirty-two per cent of
      patients received head CT and of these, 24% (37 patients) were reported to have
      pathology. Twenty-four patients underwent head CT without clinical justification
      being documented, none of which had reported pathology on CT. CONCLUSION: The
      study shows that the head injury guidelines are not being fully utilised at a
      major UK trauma hospital, resulting in 5% of patients being exposed to ionising
      radiation without apparent documented clinical justification. The NSW guideline
      has distinct differences to the CG 56, with a more complex algorithm and an
      absence of specific time frames for head CT completion. The results suggest a
      need for further education and awareness of head injury clinical guidelines.

PMID- 23551774
TI  - PET/CT mediastinal and liver FDG uptake: effects of biological and procedural
      factors.
AB  - INTRODUCTION: To establish the effects of biological and procedural factors on
      mediastinal and liver [(18) F]-fluorodeoxyglucose (FDG) uptake in oncological FDG
      positron emission tomography/computed tomography (PET/CT). METHODS: This
      retrospective study included 557 patients who had a baseline FDG PET/CT scan in
      2008 and 2009. Mediastinal and liver standardised uptake values mean normalised
      to lean body mass (SUVlbm mean) were measured in each patient. Univariate and
      multivariate regression models were established. Study population was then
      dichotomised into low and high body mass index (BMI) groups, and linear
      regression models were established for the effects of age, incubation period and
      blood glucose levels. RESULTS: BMI had the highest adjusted effect (standardised
      beta coefficient, b = 0.43) (P < 0.001) and partial correlation, adjusting for
      covariates included in the final model (r = 0.45; P < 0.001) on mediastinal FDG
      uptake. Partial correlations (r) were 0.22 for age, -0.17 for male gender, -0.25
      for incubation period and 0.14 for blood glucose (P < 0.001). The linear
      regression models showed significant differences in mediastinal FDG uptake
      between the low and high BMI groups and the effects of age, incubation period and
      basal blood glucose levels (P < 0.001). Similar results were observed for liver
      FDG uptake except the partial correlation for incubation period was r = -0.09 (P
      = 0.02). CONCLUSION: BMI has the highest effect and correlation on mediastinal
      and liver FDG uptake. FDG uptake time has a greater effect on mediastinal than
      liver SUVlbm mean.

PMID- 23551775
TI  - Choroid plexus tumours: classification, MR imaging findings and pathological
      correlation.
AB  - INTRODUCTION: Choroid plexus tumours (CPTs) are extremely rare intraventricular
      neoplasms and are prone to bleeding during surgery. The purpose of this study was
      to summarise the MR imaging characteristics of 13 CPT cases. METHODS: Magnetic
      resonance images of 13 patients (six men and seven women; mean age 21.1 years)
      with pathologically proved CPTs were retrospectively reviewed. MR findings of the
      tumours were evaluated, with emphasis on their location, size, shape, internal
      architecture, margin and pattern and degree of enhancement. Differences in signal
      intensity characteristics were also investigated on MR images and analysed
      according to histological subtypes. RESULTS: Lesions were in the lateral
      ventricles (n = 7), fourth ventricle (n = 5) and cisterna magna (n = 1), with a
      mean size of 5.0 cm (range 2.0-7.9 cm). The tumour parenchyma was a mixture of
      nodular or patchy areas of inhomogeneous isointense to slightly hyperintense
      signal on T2-weighted images. On postcontrast MR images, all lesions, except for
      one, had moderate to marked contrast enhancement. Multiple tortuous areas of
      'flow void' signal extended through all the tumours except for two. A thin
      capsule could be seen in six cases. CONCLUSION: Observation of large
      intraventricular tumours with inhomogeneity on T2-weighted images and flow void
      is suggestive of CPTs. Checking for signs of a thin capsule, extensive
      peritumoural oedema and necrosis may be useful when classifying CPTs.

PMID- 23551776
TI  - Coronary artery anomalies in adults: imaging at dual source CT coronary
      angiography.
AB  - Congenital abnormalities of the coronary arteries have an incidence of 1%, and
      most of these are benign. However, a small number are associated with myocardial
      ischaemia and sudden death. Various imaging modalities are available for coronary
      artery assessment. Recently, multi-detector CT has emerged as an accurate
      diagnostic tool for defining coronary artery anomalies. The purpose of this
      pictorial essay is to review the dual source CT appearance of congenital
      anomalies of the coronary arteries in adults.

PMID- 23551777
TI  - Embolisation of hypervascular bone tumours: a pictorial essay with literature
      review.
AB  - Bone tumours, either primary or secondary, can present in various debilitating
      manners, including pain and pathological fracture. The situation is particularly
      problematic when the tumours are hypervascular, and located in regions where a
      high risk of neurological compromise is anticipated during operation, such as in
      the spine or sacrum. In such situations, bone tumour embolisation is a useful and
      effective adjunctive treatment for reducing intra-operative blood loss. This is
      particularly relevant in primary bone tumours such as giant cell tumours and
      metastatic renal cell and thyroid tumours. With a proper pre-embolisation
      angiogram and knowledge of anatomy, careful selective cannulation of the arterial
      supplies and experience in using embolic agents, the risks of non-target
      embolisation can be kept to minimum and the best result achieved.

PMID- 23551778
TI  - Improved method of double-J ureteric stenting.
AB  - Double-J ureteral stents and antegrade stenting have been performed by
      radiologists for years. Various methods have been described, dependent on
      available equipment as well as technical expertise. As such, there is no definite
      consensus with regards to deployment of these stents. We describe an innovative
      technique, which would improve this procedure and highlight its advantages.

PMID- 23551779
TI  - Case of bilateral non-traumatic subperiosteal orbital haematomas.
AB  - Subperiosteal orbital haematoma is an uncommon entity, usually unilateral and
      caused by trauma. We present a unique case of bilateral non-traumatic
      subperiosteal orbital haematomas caused by thrombolysis and anticoagulation.

PMID- 23551780
TI  - To dot or not?: The need to redesign frontline image interpretation.

PMID- 23551781
TI  - Is radiographer commenting the answer?

PMID- 23551782
TI  - Planting the seeds of success: CT-guided gold seed fiducial marker placement to
      guide robotic radiosurgery.
AB  - Fiducial marker (FM)-guided stereotactic body radiation therapy (SBRT) allows for
      precise targeting and delivery of radiation to a tumor site. In this article, we
      briefly discuss SBRT, provide examples to describe CT-guided FM placement to
      guide SBRT, and discuss some of the associated risks and benefits. This article
      serves as a pictorial review for body imagers and interventional radiologists who
      perform CT-guided procedures and interpret diagnostic studies for oncology
      patients. CT-guided FMs were placed in patients who were appropriate candidates
      for SBRT. One week following placement, patients underwent diagnostic CT and/or
      MR examinations in order to include the FM data in the development of a treatment
      plan. From October 2007-November 2009, a total of 89 patients were implanted with
      FMs. Sites of implantation included lung, liver, bone, chest and abdominal wall,
      and peritoneum/retroperitoneum. Complications included pneumothorax and FM
      migration. Twenty-one patients (33%) with lung FM placement experienced at least
      a small pneumothorax and 6 patients (9%) required thoracostomy tubes. FM
      migration occurred in 5 patients (8%) with lung placement. SBRT provides a safer
      and more effective alternative to conventional radiotherapy, and CT-guided FM
      implantation of tumor sites increases the precision of SBRT. Technical
      improvements in FM placement can limit the complications associated with the
      procedure and further enable highly localized tumor therapy.

PMID- 23551783
TI  - HDR brachytherapy for superficial non-melanoma skin cancers.
AB  - INTRODUCTION: Our initial experience using recommended high dose per fraction
      skin brachytherapy (BT) treatment schedules, resulted in poor cosmesis. This
      study aimed to assess in a prospective group of patients the use of Leipzig
      surface applicators for High Dose Rate (HDR) brachytherapy, for the treatment of
      small non-melanoma skin cancers (NMSC) using a protracted treatment schedule.
      METHOD: Treatment was delivered by HDR brachytherapy with Leipzig applicators. 36
      Gy, prescribed to between 3 to 4 mm, was given in daily 3 Gy fractions. Acute
      skin toxicity was evaluated weekly during irradiation using the Radiation Therapy
      Oncology Group criteria. Local response, late skin effects and cosmetic results
      were monitored at periodic intervals after treatment completion. RESULTS: From
      March 2002, 200 patients with 236 lesions were treated. Median follow-up was 66
      months (range 25-121 months). A total of 162 lesions were macroscopic, while in
      74 cases, BT was given after resection because of positive microscopic margins.
      There were 121 lesions that were basal cell carcinomas, and 115 were squamous
      cell carcinomas. Lesions were located on the head and neck (198), the extremities
      (26) and trunk (12). Local control was 232/236 (98%). Four patients required
      further surgery to treat recurrence. Grade 1 acute skin toxicity was detected in
      168 treated lesions (71%) and grade 2 in 81 (34%). Cosmesis was good or excellent
      in 208 cases (88%). Late skin hypopigmentation changes were observed in 13 cases
      (5.5%). CONCLUSION: Delivering 36 Gy over 2 weeks to superficial NMSC using HDR
      brachytherapy is well tolerated and provides a high local control rate without
      significant toxicity.

PMID- 23551784
TI  - Radiation treatment compliance in the Indigenous population: the pilot Northern
      Territory experience and future directions.
AB  - INTRODUCTION: There is a perception that Indigenous patients are less likely to
      attend radiotherapy treatment. This study sought to determine if a difference in
      radiotherapy treatment compliance rates exists between Indigenous and non
      Indigenous patients. Secondly, we aimed to ascertain which patient, disease and
      treatment factors affect compliance in Indigenous patients. METHODS: All patients
      treated with radiotherapy at the Alan Walker Cancer Care Centre between March and
      October 2010 were analysed. Data regarding compliance rates (defined as those who
      chose and completed the recommended course of treatment), patient, disease and
      treatment factors were collected, and chi-squared and Fisher's exact tests were
      applied. RESULTS: A total of 41 courses were delivered to Indigenous patients and
      224 courses delivered to non-Indigenous patients in this period. There was no
      difference in compliance between Indigenous and non-Indigenous patients (83% vs.
      81%, P = 0.75). Of the factors assessed, it was found that there was an
      association between toxicity grade and compliance (P = 0.048). CONCLUSIONS: From
      this cohort, we cannot support the perception that Indigenous patients have
      overall poorer compliance with recommended radiation treatment courses. In this
      study, the only factor which correlated significantly with compliance was
      toxicity grade. It is felt that a number of factors, which negatively impact on
      compliance, can potentially be counteracted by a culturally sensitive model of
      care.

PMID- 23551785
TI  - Adjuvant breast radiotherapy using a simultaneous integrated boost: clinical and
      dosimetric perspectives.
AB  - INTRODUCTION: We sought to assess the cosmetic outcomes and the proportion of
      patients with late radiotherapy toxicity in a group of women with early-stage
      breast cancer treated with breast-conserving surgery (BCS) and adjuvant
      radiotherapy using a simultaneous integrated boost (SIB) technique. METHODS AND
      MATERIALS: Female patients with early-stage breast cancer (pT1-2 N0-1) treated
      with BCS and radiotherapy using an SIB technique were identified retrospectively
      from the departmental database. Radiotherapy consisted of 45 Gy in 25 fractions
      delivered to the whole breast with a simultaneous forward-planned conformal boost
      to the tumour bed of 60 Gy in 25 fractions. Demographic data, as well as
      prospectively collected measures of toxicity and cosmesis, were recorded and
      analysed. RESULTS: Fifty-five eligible patients were treated between 2009 and
      2011. The median age was 61 years (range, 31 to 81 years). Median follow-up was
      13.3 months. Late toxicities (including oedema, pigmentation, telangiectasia,
      fibrosis, osteonecrosis and pain) were graded using Common Terminology Criteria
      for Adverse Events v3.0 criteria. Grade 0, 1 and 2 toxicities were assigned to
      52.8%, 43.4% and 3.8% of patients, respectively. There were no cases of grade 3
      or greater toxicity. Ninety-eight per cent had a good or excellent cosmetic
      outcome based on independent assessment by both the patient and physician. One
      patient developed a second primary contralateral breast cancer. There were no
      cases of local recurrence. CONCLUSION: The use of a conformal SIB technique is
      proposed as a mode of delivering adjuvant radiotherapy in early-stage breast
      cancer. This schedule is convenient for the patient given the shortened overall
      treatment time. Additionally, the SIB technique seems to be well tolerated, with
      minimal toxicity and acceptable cosmetic outcomes. Finally, there are dosimetric
      benefits with respect to target coverage and reduction of dose and dose per
      fraction to organs at risk.

PMID- 23551786
TI  - Novel 3D conformal technique for treatment of choroidal melanoma with external
      beam photon radiotherapy.
AB  - INTRODUCTION: To report a 3D conformal radiotherapy (3D-CRT) technique that
      utilises a specific eye immobilisation and treatment set-up method as an
      alternative to stereotactic radiotherapy (SRT), for treatment of juxtapapillary
      choroidal melanoma (CM) and report early treatment outcomes of this technique.
      METHODS: A contact lens and rod system was designed to provide eye immobilisation
      and a treatment reference point for 3D-CRT. The technique is described in detail
      in the body of the paper. A retrospective chart review was conducted to report
      freedom from local progression (FFLP) and radiation toxicity in a cohort of
      patients treated with a dose of 50 Gy in five fractions. RESULTS: Eleven eligible
      patients with juxtapapillary CM were treated between 2003 and 2009. The median
      follow-up was 3.2 years (range 1.2-5.3). The FFLP was 100% (95% confidence
      interval 71.5-100). The reproducibility of the set-up and eye immobilisation for
      fractionation was excellent. The mean dose to the planning target volume was 51.4
      Gy (interquartilic range 51.0-51.9). Normal tissue dose constraints were
      achieved; however, the quality of the 3D-CRT plan was variable. The highest acute
      radiation toxicity score was Common Toxicity Criteria version 3 grade 1. Vision
      outcomes were poor. CONCLUSION: In this small series, a novel non-stereotactic
      technique was found to be an accurate method for the treatment of CM with a high
      rate of freedom from tumour progression, in keeping with the SRT series. The
      quality of the conformal plan was variable. Investigation of the optimal dose
      fractionation schedule to minimise late radiation toxicity without compromise of
      tumour control is the focus of ongoing clinical research at our centre.

PMID- 23551787
TI  - Defining a dose-response relationship for prostate external beam radiotherapy.
AB  - INTRODUCTION: We aimed to quantify a relationship between radiotherapy dose and
      freedom from biochemical failure (FFBF) in low- and intermediate-risk prostate
      cancer. To reduce confounding we used data with a standardised end-point, mature
      follow-up, low competing risk of metastatic failure, conventional fractionation
      and separate reporting for outcomes with hormonal therapy (HT). METHODS: A
      systematic review of the literature was carried out. Studies that reported the
      use of radiotherapy alone in 1.8-2 Gy fractions in low- and intermediate-risk
      prostate cancer were included. The primary end-point was Phoenix definition 5
      year FFBF. A logistic regression was used to quantify the dose-response
      relationship. RESULTS: Data from eight studies with 3037 patients met the
      inclusion criteria. The data from 810 low-risk patients and 2245 intermediate
      risk patients were analysed. A strong association between radiotherapy dose and
      FFBF was found in low- and intermediate-risk patients managed with radiotherapy
      alone. In low-risk patients not treated with HT the dose required to achieve 50%
      biochemical tumour control (TCD50 ) is 52.0 Gy and the slope of the dose-response
      curve at TCD50 (gamma50 ) is 2.1%/Gy. At 78 Gy this represented a FFBF of 90.3%.
      In intermediate-risk patients not treated with HT the TCD50 is 64.7 Gy and
      gamma50 is 3.2%/Gy. At 78 Gy this translated into a FFBF of 84.3%. HT had a small
      effect for low-risk patients and an inconsistent effect for intermediate-risk
      men. CONCLUSION: A strong association was found between radiation dose and
      biochemical outcome in both low- and intermediate-risk patients. Standardised
      reporting of results from future studies will make future analyses more robust.

PMID- 23551788
TI  - Quality improvements in prostate radiotherapy: outcomes and impact of
      comprehensive quality assurance during the TROG 03.04 'RADAR' trial.
AB  - INTRODUCTION: The Trans-Tasman Radiation Oncology Group 03.04 'Randomised
      Androgen Deprivation and Radiotherapy' multicentre prostate cancer trial examined
      the optimal duration of androgen deprivation in combination with dose-escalated
      radiotherapy. Rigorous quality assurance (QA) processes were undertaken to ensure
      the validity and reliability of the radiation therapy treatment plan data.
      METHOD: QA processes included a planning benchmarking exercise and a periodic
      audit of target and normal tissue delineation. Centralised electronic review of
      digital plan data for external-beam radiotherapy was undertaken to detect
      protocol variations. The impact of clinical factors and feedback to submitting
      centres during the trial on variation rates was investigated. RESULTS: Twenty
      three centres across Australia and New Zealand recruited 1071 participants to the
      trial. Treatment plans for 754 participants receiving external-beam treatment
      alone were reviewed. From these, 1185 minor and 86 major variations were
      identified, leading to feedback to treating centres to reduce variations for
      subsequent patients' treatment and plans, suggesting improvement in treatment
      quality through these QA programs. Participant anatomical factors (delineated
      clinical target volume and rectal volume) and treatment planning factors (beam
      energy, beam definition and patient position orientation) were found to
      significantly impact variation rates. The dummy run demonstrated disagreement in
      identification of the base of the prostate and the superior extent of the rectum.
      Feedback from the periodic audit led to a change of practice at five contributing
      centres. CONCLUSION: The application of a suite of complementary QA activities
      allows the quality of trial data to be optimised and quantified, and can provide
      a catalyst for reforming treatment practices.

PMID- 23551790
TI  - Nurse practitioner job satisfaction: looking for successful outcomes.
AB  - AIMS AND OBJECTIVES: To examine overall job satisfaction and its association with
      extrinsic and intrinsic characteristics of job satisfaction among nurse
      practitioners at the chosen practice site. The objectives were to identify
      relevant retention and recruitment strategies, from the nurse practitioners
      perspective, by examining (1) what role aspects are most satisfying, and (2)
      approaches for successful, professional development and integration in the role.
      BACKGROUND: Supportive professional practice environments are particularly
      important to nurses' satisfaction with their work and the quality of patient care
      provided. Hence, research that examines nurse practitioners practice implications
      and barriers in today's healthcare system is essential. DESIGN/METHODS: A
      descriptive-correlational design using survey methodology. A nonprobability
      sample of convenience was used. The outcome measures were: The Misener Nurse
      Practitioner Job Satisfaction Scale and two investigator-developed surveys.
      RESULTS: Participants expressed dissatisfaction with professional and monetary
      recognition, assertive influence, administrative support and collegial
      relationships. CONCLUSIONS: Interaction of subscale factors on overall job
      satisfaction and demographic survey findings has important implications for
      health administrators and nurse practitioners in similar organisations. RELEVANCE
      TO CLINICAL PRACTICE: Stakeholders in healthcare milieus need to be fully engaged
      in the redesign of the American healthcare system heeding the recommendations of
      the Institute of Medicine to provide safer health systems to the public. By doing
      this, issues related to frustration by nurse practitioners related to job
      satisfaction will be addressed. The need for cooperation, participation,
      collaboration and instrumental communication are essential in the delivery of
      safe, quality patient care. A better understanding of intrinsic professional
      rewards needs to be learned by nurse practitioners who want to seek professional
      satisfaction and engage in the survival and growth of the profession. Nurse
      practitioners armed with this translational information have viable agenda items
      that can be negotiated into extrinsic rewards.

PMID- 23551791
TI  - Educational interventions in neurology: a comprehensive systematic review.
AB  - A fear of neurology and neural sciences (neurophobia) may have clinical
      consequences. There is therefore a need to formulate an evidence-based approach
      to neurology education. A comprehensive systematic review of educational
      interventions in neurology was performed. BEI, Cochrane Library, Dialog Datastar,
      EBSCO Biomedical, EBSCO Psychology & Behavioral Sciences, EMBASE, ERIC, First
      Search, MDConsult, Medline, Proquest Medical Library and Web of Knowledge
      databases were searched for all published studies assessing interventions in
      neurology education among undergraduate students, junior medical doctors and
      residents up to and including July 2012. Two independent literature searches were
      performed for relevant studies, which were then classified for level of evidence
      using the Centre of Evidence-based Medicine criteria and four levels of
      Kirkpatrick educational outcomes. One systematic review, 16 randomized controlled
      trials (RCTs), nine non-randomized cohort/follow-up studies, 33 case series or
      historically controlled studies and three mechanism-based reasoning studies were
      identified. Educational interventions showed favourable evaluation or assessment
      outcomes in 15 of 16 (94%) RCTs. Very few studies measured subsequent clinical
      behaviour (two studies) and patient outcomes (one study). There is very little
      high quality evidence of demonstrably effective neurology education. However,
      RCTs are emerging, albeit without meeting comprehensive educational criteria. An
      improving evidence base in the quality of neurology education will be important
      to reduce neurophobia.

PMID- 23551792
TI  - Dehydrated egg white: an allergen source for improving efficacy and safety in the
      diagnosis and treatment for egg allergy.
AB  - BACKGROUND: Raw and cooked eggs are used as allergens in oral food challenge
      (OFC). Raw egg is the best option, as it keeps proteins intact and retains their
      allergenicity, albeit microbiologically safe manipulation is difficult.
      Therefore, the use of dehydrated egg white (DEW) could improve the efficacy and
      safety profile of OFC. The aim of the study was to compare the allergenicity of
      DEW, a product that undergoes a double heat treatment (pasteurization and
      drying), with that of raw egg white (REW) and determine the efficacy of DEW in
      the diagnosis of egg allergy. METHODS: We conducted a prospective study of 40 egg
      allergic patients who visited our outpatient clinic. Each patient underwent OFC
      with DEW and REW to determine the correlation between the tests. DEW and REW
      extracts were analyzed using SDS-PAGE. We compared the allergenicity of both
      extracts using IgE immunoblotting with a serum pool from patients with positive
      OFC results. RESULTS: Ten patients (25%) had positive OFC results with both DEW
      and REW, and the doses that triggered an allergic reaction in each patient were
      similar (p > 0.05). All 30 patients (75%) with a negative OFC result with DEW
      also had negative OFC results with REW. SDS-PAGE and IgE immunoblotting revealed
      that the protein composition and IgE-binding capacity of both extracts were
      virtually identical. CONCLUSIONS: This is the first time that it is shown that
      the allergenicity of commercially available DEW is equivalent to raw egg whites.
      In vivo and in vitro tests showed that processing of DEW does not affect the
      allergenicity of egg proteins. DEW is an effective and microbiologically safer
      source of allergen for the diagnosis of egg allergy. Furthermore, DEW can be used
      in egg oral immunotherapy.

PMID- 23551793
TI  - Reverse activated hyrax pressure appliance for treatment of a keloid located at
      auricula helix.
AB  - Keloids are considered aberrations of the wound healing process, and various
      treatment regimens are described depending on the morphology and size of the
      lesion. Compression therapy using custom-made pressure clips or splints is widely
      used for the treatment of keloids. The most common complication of this therapy
      is ulceration due to excessive soft tissue pressure, resulting in delays and
      prolonged treatment time. This article describes the fabrication of a custom-made
      pressure appliance for the treatment of a keloid located at the auricle helix.
      The pressure appliance can be modified to fit the auricle helix and covers the
      area needing pressure. 

PMID- 23551794
TI  - Assessment of poly-L-lysine dendrigrafts for virus concentration in water: use of
      MS2 bacteriophage as proof of concept.
AB  - AIMS: Virus detection has often been difficult due to a low concentration in
      water. In this study, we developed a new procedure based on concentration of
      virus particles on an innovative support: poly-L-lysine dendrigrafts (DGL),
      coupled with directed nucleic acid extraction and real-time PCR quantification.
      METHODS AND RESULTS: This method was evaluated using the bacteriophage MS2 as a
      model virus. This virus exhibited the size and structural properties of human
      pathogenic enteric viruses and has often been used to assess new supports of
      concentration. Moreover, this bacteriophage is also a faecal contamination
      indicator. In this study, many water filtration conditions were tested (volume of
      water, concentration, etc.), and more than 80% of bacteriophage were recovered
      after filtration on polymer, in most conditions. We demonstrated that the method
      was linear (slope = 0.99 +/- 0.04 and Y intercept when x = -0.02 +/- 0.28), valid
      (as manipulators, tested concentrations, volumes of sample and batch of polymer
      did not have any influence on concentration) and sensitive (allowing to
      concentrate up to 16,600-fold 1 l of sample and to detect and quantify down to
      750 GC l(-1) and 7500 GC l(-1), respectively). CONCLUSIONS: To conclude, this
      support exhibits high interest to retain viruses and to allow to detect low
      concentration of virus in water. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      gives valuable advance in the methods of concentration and diagnosis of virus in
      water.

PMID- 23551795
TI  - Serum sodium based modification of the MELD does not improve prediction of
      outcome in acute liver failure.
AB  - BACKGROUND: Acute liver failure (ALF) is a devastating clinical syndrome with a
      high mortality rate. The MELD score has been implied as a prognostic tool in ALF.
      Hyponatremia is associated with lethal outcome in ALF. Inclusion of serum sodium
      (Na) into the MELD score was found to improve its predictive value in cirrhotic
      patients. Therefore the aim of this study was to determine whether inclusion of
      serum Na improves the predictive value of MELD in ALF compared to established
      criteria. METHODS: In a prospective single center study (11/2006-12/2010), we
      recruited 108 consecutive ALF patients (64% females / 36% males), who met the
      criteria defined by the "Acute Liver Failure Study Group Germany". Upon
      admission, clinical and laboratory data were collected, King's College Criteria
      (KCC), Model of End Stage Liver Disease score (MELD), and serum sodium based
      modifications like the MELD-Na score and the United Kingdom Model of End Stage
      Liver Disease score (UKELD) were calculated and area under the receiver operating
      characteristic curve analyses were performed regarding the prediction of
      spontaneous recovery (SR) or non-spontaneous recovery (NSR; death or
      transplantation). RESULTS: Serum bilirubin was of no prognostic value in ALF, and
      Na also failed to predict NSR in ALF. The classical MELD score was superior to
      sodium-based modifications and KCC. CONCLUSIONS: We validated the prognostic
      value of MELD-Na and UKELD in ALF. Classic MELD score calculations performed
      superior to KCC in the prediction of NSR. Serum Na and Na-based modifications of
      MELD did not further improve its prognostic value.

PMID- 23551796
TI  - Genetic variability in Microsporum canis isolated from cats, dogs and humans in
      Brazil.
AB  - Dermatophytosis caused by Microsporum canis is a heterogeneous disease with
      variable clinical manifestations. M. canis is a zoophilic dermatophyte and the
      most frequent fungi isolated from dogs, cats and children in Brazil. The aim of
      this study was to investigate the genetic variability of M. canis isolates from
      different animal species using two microsatellite markers, namely, McGT(13) and
      McGT(17), and to correlate the results with the clinical and epidemiological
      patient data in Brazil. The study included a global set of 102 M. canis strains,
      including 37 symptomatic cats, 35 asymptomatic cats, 19 human patients with
      tinea, 9 asymptomatic dogs and 2 symptomatic dogs. A total of 14 genotypes were
      identified, and 6 large populations were distinguished. There was no correlation
      between these multilocus genotypes and the clinical and epidemiological data,
      including the source, symptomatology, clinical picture, breed, age, sex, living
      conditions and geographic location. These results demonstrate that the use of
      microsatellite polymorphisms is a reliable method for the differentiation of M.
      canis strains. However, we were unable to demonstrate a shared clinical and
      epidemiological pattern among the same genotype samples. 

PMID- 23551797
TI  - Systemic, renal, and colonic effects of intravenous and enteral rehydration in
      horses.
AB  - BACKGROUND: Intravenous (IV) and intragastric (IG) administration of fluid
      therapy are commonly used in equine practice, but there are limited data on the
      systemic, renal, and enteric effects. HYPOTHESIS: IV fluid administration will
      increase intestinal and fecal hydration in a rate-dependent manner after
      hypertonic dehydration, but will be associated with significant urinary water and
      electrolyte loss. Equivalent volumes of IG plain water will result in
      comparatively greater intestinal hydration with less renal loss. ANIMALS: Six
      Thoroughbred geldings. METHODS: Experimental study. 6 by 6 Latin square design
      investigating constant rate IV administration at 50, 100, and 150 mL/kg/d over 24
      hours in horses dehydrated by water deprivation. Equivalent volumes of IG plain
      water were administered by 4 bolus doses over 24 hours. RESULTS: Water
      deprivation resulted in a significant decrease in the percentage of fecal water,
      and increases in serum and urine osmolality. IV fluids administered at 100 and
      150 mL/kg/d restored fecal hydration, but increasing the rate from 100 to 150
      mL/kg/d did not confer any additional intestinal benefit, but did result in
      significantly greater urine production and sodium loss. Equivalent 24-hour
      volumes of plain water resulted in greater intestinal water and less urine
      output. CONCLUSIONS AND CLINICAL IMPORTANCE: IV polyionic isotonic fluids can be
      used to hydrate intestinal contents in situations where enteral fluids are
      impractical. IV fluids administered at three times maintenance are no more
      efficacious and might be associated with adverse physiological findings after
      withdrawal. Bolus dosing of IG water can be used to restore intestinal water with
      minimal adverse effects.

PMID- 23551798
TI  - The effects of assertiveness training in patients with schizophrenia: a
      randomized, single-blind, controlled study.
AB  - AIMS: In this study, we investigated the effects of group assertiveness training
      on assertiveness, social anxiety and satisfaction with interpersonal
      communication among patients with chronic schizophrenia. BACKGROUND: Only limited
      studies highlighted the effectiveness of group assertiveness training among
      inpatients with schizophrenia. Given the lack of group assertiveness training
      among patients with schizophrenia, further development of programmes focusing on
      facilitating assertiveness, self-confidence and social skills among inpatients
      with chronic schizophrenia is needed. DESIGN: This study used a prospective,
      randomized, single-blinded, parallel-group design. METHODS: This study employed a
      prospective, randomized, parallel-group design. Seventy-four patients were
      randomly assigned to experimental group receiving 12 sessions of assertiveness
      training, or a supportive control group. Data collection took place for the
      period of June 2009-July 2010. RESULTS: Among patients with chronic
      schizophrenia, assertiveness, levels of social anxiety and satisfaction with
      interpersonal communication significantly improved immediately after the
      intervention and at the 3-month follow-up in the intervention group. The results
      of a generalized estimating equation (GEE) indicated that: (1) assertiveness
      significantly improved from pre- to postintervention and was maintained until the
      follow-up; (2) anxiety regarding social interactions significantly decreased
      after assertiveness training; and (3) satisfaction with interpersonal
      communication slightly improved after the 12-session intervention and at the 3
      month follow-up. CONCLUSION: Assertivenss training is a non-invasive and
      inexpensive therapy that appears to improve assertiveness, social anxiety and
      interpersonal communication among inpatients with chronic schizophrenia. These
      findings may provide a reference guide to clinical nurses for developing
      assertiveness-training protocols.

PMID- 23551799
TI  - ALT cut-off value for blood donor screening should be established for servicemen
      separately.

PMID- 23551800
TI  - Drug provocation tests: up-date and novel approaches.
AB  - SUMMARY: Drug provocation tests (DPTs) are often needed when evaluating patients
      with suspected drug hypersensitivity reactions. General considerations on DPTs,
      with regard to indications, contraindications, methods, limitations and
      interpretations have been thoroughly addressed and various protocols are
      published. However, the field of drug allergy is changing and DPTs make no
      exception. Novel (or sometimes, simply renewed) approaches arise, awaiting to be
      either validated or refuted in larger studies in the future. Instead of covering
      the whole topic of DPTs, this paper will address these recent and challenging
      aspects.

PMID- 23551801
TI  - Reply to: 'the discovery of a new class of synaptic transmitters in smooth muscle
      fifty years ago and amelioration of coronary artery thrombosis'.

PMID- 23551802
TI  - Cerebellum-dependent associative learning deficits in primary dystonia are
      normalized by rTMS and practice.
AB  - Eyeblink classical conditioning (EBCC) is a cerebellum-dependent paradigm of
      associative motor learning, and abnormal EBCC is a neurophysiological indicator
      of cerebellar dysfunction. We have previously demonstrated impaired EBCC in
      patients with primary dystonia, but it remains uncertain if this represents
      actual cerebellar pathology or reflects a functional cerebellar disruption. We
      examined this further by: (1) studying acquisition and retention of EBCC in a
      second session in eight patients with cervical dystonia (CD) who had a first
      session 7-10 days earlier; and (2) by investigating the potential of continuous
      theta burst stimulation (cTBS) over the right cerebellar hemisphere to modify a
      first-ever EBCC session in 11 patients with CD. EBCC data of eight healthy
      controls previously studied were used for additional between-group comparisons.
      We observed an improvement of EBCC in a second session in patients with CD, which
      is in contrast to patients with proven cerebellar pathology who do not show
      further improvement of EBCC in additional sessions. We also found that cerebellar
      cTBS paradoxically normalized EBCC in patients with CD, while we previously
      showed that it disrupts EBCC in healthy volunteers. Combined, these two
      experiments are in keeping with a functional and reversible disruption of the
      cerebellum in dystonia, a phenomenon that is probably secondary to either
      cerebellar compensation or to cerebellar recruitment in the abnormal sensorimotor
      network. 

PMID- 23551803
TI  - A double-blind, placebo-controlled study of adjunctive calcitonin nasal spray in
      acute refractory mania.
AB  - OBJECTIVES: Calcitonin, a neuropeptide, has been shown in preliminary double
      blind trials to reduce agitation in patients with acute mania. Given that it has
      effects similar to those of lithium and anticonvulsants on modulation of second
      messenger signaling pathways and stabilization of neuronal membranes, this study
      examined the efficacy of calcitonin nasal spray in treating acute manic symptoms
      in patients with treatment-resistant mania using a double-blind, placebo
      controlled design. METHODS: A total of 46 hospitalized patients experiencing
      either a manic or a mixed episode, who were refractory to treatment with adequate
      doses of either a mood stabilizer or an antipsychotic, or a mood
      stabilizer/antipsychotic combination, and had a score of >=16 on the Young Mania
      Rating Scale (YMRS), were randomized to receive adjunctive nasal calcitonin 200
      IU (n = 24) or saline (n = 22) spray for three weeks. The primary efficacy
      measure was the change in YMRS scores using the last observation carried forward
      (LOCF) method. RESULTS: The clinical and demographic characteristics were similar
      between the groups. Patients had a mean YMRS score of 26 in the placebo group and
      a mean score of 25 in the calcitonin group. There were no significant differences
      in YMRS scores or percentage responders at three weeks between patients who
      received calcitonin and those who received placebo. There were also no
      significant differences in change scores on any other scales. Few patients
      experienced any adverse events. CONCLUSIONS: This study does not support the use
      of nasal calcitonin in the treatment of treatment-resistant mania.

PMID- 23551804
TI  - Thoracoscopic esophagectomy with extended lymph node dissection in the left
      lateral position: technical feasibility and oncologic outcomes.
AB  - The aim of this study was to estimate the technical and oncologic feasibility of
      video-assisted thoracoscopic radical esophagectomy (VATS) in the left lateral
      position. From January 2003 to December 2011, 132 patients with esophageal cancer
      underwent VATS. The mean duration of the thoracic procedure and the entire
      procedure was 294 +/- 88 and 623 +/- 123 minutes, respectively. Mean blood loss
      during the thoracic procedure and the entire procedure was 313 +/- 577 and 657 +/
      719 g, respectively. The mean number of dissected thoracic lymph nodes was 32.6
      +/- 12.9. There were four in-hospital deaths (3.0%); two patients (1.5%) died of
      acute respiratory distress syndrome and two patients (1.5%) died of tumor
      progression. Postoperative unilateral or bilateral recurrent laryngeal nerve
      (RLN) palsy, or pneumonia was found in 33 (25.0%), 21 (15.9%), and 27(20.5%)
      patients, respectively. The patients were divided into the first 66 patients who
      underwent VATS (Group 1) and the subsequent 66 patients (Group 2). The numbers of
      cases who underwent neoadjuvant or induction chemotherapy for T4 tumor and
      intrathoracic anastomosis were higher in Group 2 than in Group 1. The duration of
      the procedure, amount of blood loss, and the number of dissected thoracic lymph
      nodes were not different between the two groups. The total number of dissected
      lymph nodes was higher in Group 2 than in Group 1 (72.6 +/- 27.8 vs. 62.6 +/-
      21.6, P = 0.023). The rate of bilateral RLN palsy was less in Group 2 than in
      Group 1 (7.6% vs. 24.2%, P = 0.042). The mean follow-up period was 38.7 months.
      Primary recurrence consisted of hematogenous, lymphatic, peritoneal
      dissemination, pleural dissemination, and locoregional in 15 (11.3%), 20 (15.1%),
      3 (2.3%), 4 (3.0%), and 5 patients (3.8%), respectively. The rate of regional
      lymph node recurrence within the dissection field was only 4.5%. The prognosis of
      patients with lymph node metastasis was significantly poorer than that of
      patients without lymph node metastasis. However, the prognosis of the 11 cases
      that had metastasis only around RLNs was similar to that of node-negative cases.
      Thirteen patients with pathological remnant tumor (R1 or R2) did not survive
      longer than 5 years at present. The overall 5-year survival rate of stage I, II,
      and III disease after curative VATS was 82.2%, 77.0%, and 52.3%, respectively.
      Expansion of VATS criteria for patients after induction chemotherapy for T4 tumor
      or thoracoscopic anastomosis did not adversely affect the surgical results by
      experience. Although the VATS procedure is accompanied by a certain degree of
      morbidity including RLN palsy and pulmonary complications, VATS has an excellent
      locoregional control effect. In addition, the favorable survival after VATS shows
      that the procedure is oncologically feasible. 

PMID- 23551806
TI  - Total oxidant, antioxidant, and paraoxonase levels in babies born to pre
      eclamptic mothers.
AB  - AIM: The aim of this study was to investigate the oxidant-antioxidant status in
      babies born to pre-eclamptic mothers (BBPM). MATERIAL AND METHODS: The
      paraoxonase (PON)-1, total antioxidant status (TAS), and total oxidant status
      (TOS) levels were measured in the cord blood and venous blood (7th day) of BBPM
      (n = 31) and babies born to normotensive mothers (n = 25). RESULTS: The PON-1 and
      TOS levels in the cord blood and venous blood on the 7th day were not
      significantly different between the two groups; however, the cord blood TAS
      levels were higher in BBPM (P = 0.001), and the TAS levels in the venous blood
      were higher in the control group (P = 0.021). Furthermore, the cord blood PON-1
      levels of babies born to severely pre-eclamptic mothers (n = 18) were higher than
      those of babies born to moderately pre-eclamptic mothers (n = 13) (P = 0.042).
      There were no differences in the cord blood TAS and TOS levels and venous blood
      PON-1, TAS, and TOS levels between babies born to severely and moderately pre
      eclamptic mothers. CONCLUSION: The increased TAS levels found in the cord blood
      of BBPM indicate that the fetus is protected against oxidative damage caused by
      increased oxidative stress in the mother. To the best of our knowledge, this is
      the first study in the published work investigating PON-1 levels in BBPM.

PMID- 23551805
TI  - Task-correlated facial and head movements in classifier-based real-time FMRI.
AB  - BACKGROUND: Real-time fMRI is especially vulnerable to task-correlated movement
      artifacts because statistical methods normally available in conventional analyses
      to remove such signals cannot be used in the context of real-time fMRI. Multi
      voxel classifier-based methods, although advantageous in many respects, are
      particularly sensitive. Here we systematically studied various movements of the
      head and face to determine to what extent these can "masquerade" as signal in
      multi-voxel classifiers. METHODS: Ten subjects were instructed to move
      systematically (twelve instructed movements) throughout fMRI exams and data from
      a previously published real-time study was also analyzed to determine the extent
      to which non-neural signals contributed to the high reported accuracy in
      classifier output. RESULTS: Of potential concern, whole-brain classifiers based
      solely on movements exhibited false positives in all cases (P < .05). Artifacts
      were also observed in the spatial activation maps for two of the twelve movement
      tasks. In the retrospective analysis, it was determined that the relatively high
      reported classification accuracies were (fortunately) mostly explainable by
      neural activity, but that in some cases performance was likely dominated by
      movements. CONCLUSION: Movement tasks of many types (including movements of the
      eyes, face, and body) can lead to false positives in classifier-based real-time
      fMRI paradigms.

PMID- 23551807
TI  - Xenotransplantation literature update, January-February 2013.

PMID- 23551808
TI  - Validity and reliability of a smartphone application for the assessment of penile
      deformity in Peyronie's disease.
AB  - INTRODUCTION: Available methods to evaluate men with Peyronie's disease (PD) are
      limited by the inability to accurately and reproducibly measure penile deformity.
      AIM.: The study aims to evaluate the performance of a smartphone application for
      the measurement of penile curvature and narrowing. METHODS: A smartphone
      application, the University of Washington Peyronie's Examination Network (UWPEN),
      was developed for this purpose. To assess penile curvature, 15 single cylinders
      of malleable penile prostheses were molded to varying curvature angles. Three
      blinded observers nonsequentially measured the angle of curvature for each
      prosthetic cylinder using a protractor, goniometer, and UWPEN. To assess girth
      narrowing, six clay models of the penile shaft were constructed to represent
      conditions of normal, partial hourglass, circumferential hourglass, and pencil
      narrowing. Girth was measured using a ruler and UWPEN by the same blinded
      observers. MAIN OUTCOME MEASURES: Statistical analyses compared intertest,
      interobserver, and intraobserver reliability using the interclass correlation
      coefficient (ICC). An ICC above 0.75 indicates excellent reproducibility among
      measurements. RESULTS: Intertest reliability for angle measurements yielded an
      ICC for the three methods of 1.000. Separately, the ICC for UWPEN vs. the
      goniometer and protractor was 0.999 and 0.999, respectively. The interobserver
      ICC for UWPEN, goniometer, and protractor was 0.998, 0.999, and 1.000,
      respectively. Intertest reliability for girth narrowing measurements yielded an
      ICC of 0.991. The interobserver ICC for girth narrowing for UWPEN and the ruler
      was 0.978 and 0.986, respectively. Intraobserver ICC for angle measurements and
      girth narrowing showed high reliability for all observers and methods.
      CONCLUSIONS: The performance of UWPEN is comparable with and highly correlated
      with angle measurements obtained from the goniometer and protractor as well as
      with girth narrowing measurements obtained from a ruler. Measurements are
      reproducible among different observers. UWPEN may provide a noninvasive,
      accurate, reliable, and widely accessible method to characterize and track PD
      over time.

PMID- 23551809
TI  - Double-chambered right ventricle with pulmonary valve endocarditis.
AB  - We describe a rare case of pulmonary valve endocarditis associated with a double
      chambered right ventricle in an adolescent male highlighting the two-dimensional
      and three-dimensional transthoracic echocardiographic findings. He was managed
      with aggressive antibiotic therapy followed by surgery. The echocardiographic
      findings were confirmed during surgery. 

PMID- 23551810
TI  - Carbonic anhydrase IX (CAIX) is not an independent predictor of outcome in
      patients with clear cell renal cell carcinoma (ccRCC) after long-term follow-up.
AB  - OBJECTIVE: To evaluate carbonic anhydrase IX (CAIX) expression as an independent
      prognostic marker for clear cell renal cell carcinoma (ccRCC). With recent
      smaller studies showing conflicting results, we aimed to update our initial
      analysis in 2007 with an additional 5-year follow-up. PATIENTS AND METHODS: We
      provided long-term follow-up of the same cohort used in our 2007 study (730
      patients with unilateral, sporadic ccRCC treated surgically between 1990 and
      1999). Associations of CAIX expression with RCC death and distant metastases were
      evaluated using Cox proportional hazards regression models. RESULTS: CAIX was
      expressed in 708 (97.0%) of the specimens; 163 tumours (22.3%) had low (<=85%)
      expression and 567 (77.7%) high (>85%) expression. There were 483 deaths and 265
      RCC-specific deaths. The median follow-up for the 247 patients still under
      observation was 13.8 years. Univariately, low CAIX expression was associated with
      an increased risk of RCC death vs high expression (hazard ratio 1.62; P < 0.001).
      Low CAIX expression was not statistically significantly associated with RCC death
      or distant metastases after adjusting for nuclear grade or coagulative tumour
      necrosis. CONCLUSION: After additional long-term follow-up of our large cohort,
      our results continue to suggest that CAIX is not an independent prognostic marker
      for ccRCC.

PMID- 23551811
TI  - Identification and characterization of the pyrokinin/pheromone biosynthesis
      activating neuropeptide family of G protein-coupled receptors from Ostrinia
      nubilalis.
AB  - Insects have two closely related G protein-coupled receptors belonging to the
      pyrokinin/pheromone biosynthesis activating neuropeptide (pyrokinin/PBAN) family,
      one with the ligand PBAN or pyrokinin-2 and another with diapause hormone or
      pyrokinin-1 as a ligand. A related receptor is activated by products of the capa
      gene, periviscerokinins. Here we characterized the PBAN receptor and the diapause
      hormone receptor from the European corn borer, Ostrinia nubilalis. We also
      identified a partial sequence for the periviscerokinin receptor. Quantitative PCR
      of mRNA for all three receptors indicated differential expression in various life
      stages and tissues. All three splice variants of the PBAN receptor were
      identified with all variants found in pheromone gland tissue.
      Immunohistochemistry of V5 tags of expressed receptors indicated that all three
      variants and the diapause hormone receptor were expressed at similar levels in
      Spodoptera frugiperda 9 (Sf9) cells. However, the A- and B-variants were not
      active in our functional assay, which confirms studies from other moths.
      Functional expression of the C-variant indicated that it is has a 44 nM half
      effective concentration for activation by PBAN. The diapause hormone receptor was
      activated by diapause hormone with a 150 nM half effective concentration.

PMID- 23551812
TI  - Unexpected collapse of healthy newborn infants: risk factors, supervision and
      hypothermia treatment.
AB  - AIM: To determine the occurrence and risk factors of sudden unexpected postnatal
      collapse (SUPC) in presumably healthy newborn infants. METHODS: All live-born
      infants during a 30-month period, in five major delivery wards in Stockholm, were
      screened, and possible cases of SUPC thoroughly investigated. Infants were >=35
      weeks of gestation, had an Apgar score >8 at 10 min and collapsed within 24 h
      after birth. Maternal, infant, event characteristics and outcome data were
      collected. RESULTS: Twenty-six cases of SUPC were found among 68 364 live-born
      infants, an incidence of 38/100 000 live births. Sixteen of these cases of SUPC
      required resuscitation with ventilation >1 min, and 14 of these remained
      unexplained (21/100 000). Fifteen of the 26 children were found in a prone
      position, during skin-to-skin contact, 18 were primipara, and 13 occurred during
      unsupervised breastfeeding at <2 h of age. Three cases occurred during smart
      cellular phone use by the mother. Five developed hypoxic-ischaemic encephalopathy
      (HIE) grade 2, and 4 underwent hypothermia treatment. Twenty-five infants had a
      favourable neurological outcome. CONCLUSION: SUPC in apparent healthy babies is
      associated with initial, unsupervised breastfeeding, prone position, primiparity
      and distractions. Guidelines outlining the appropriate monitoring of newborns and
      safe early skin-to-skin contact should be implemented.

PMID- 23551815
TI  - The plover neurotranscriptome assembly: transcriptomic analysis in an ecological
      model species without a reference genome.
AB  - We assembled a de novo transcriptome of short-read Illumina RNA-Seq data
      generated from telencephalon and diencephalon tissue samples from the Kentish
      plover, Charadrius alexandrinus. This is a species of considerable interest in
      behavioural ecology for its highly variable mating system and parental behaviour,
      but it lacks genomic resources and is evolutionarily distant from the few
      available avian draft genome sequences. We assembled and identified over 21,000
      transcript contigs with significant expression in our samples, showing high
      homology to exonic sequences in avian draft genomes. From these, we identified
      >31,000 high-quality SNPs and > 2500 simple sequence repeats (SSRs). We also
      analysed expression patterns in our data to identify potential candidate genes
      related to differences in male and female behaviour, identifying over 200
      nonoverlapping putative autosomal transcripts that show significant expression
      differences between males and females. Gene ontology analysis revealed that
      female-biased transcripts were significantly enriched for cerebral functions
      related to learning, cognition and memory, and male-biased transcripts were
      mostly enriched for terms related to neural function such as neuron projection
      and synapses. This data set provides one of the first de novo transcriptome
      assemblies from non-normalized short-read next-generation data and outlines an
      effective strategy for measuring sequence and expression variability
      simultaneously without the aid of a reference genome.

PMID- 23551813
TI  - Herd prevalence of Enterobacteriaceae producing CTX-M-type and CMY-2 beta
      lactamases among Japanese dairy farms.
AB  - AIMS: To determine the herd prevalence of Enterobacteriaceae producing CTX-M-type
      extended-spectrum beta-lactamases (ESBLs) among 381 dairy farms in Japan. METHODS
      AND RESULTS: Between 2007 and 2009, we screened 897 faecal samples using BTB
      lactose agar plates containing cefotaxime (2 MUg ml(-1)). Positive isolates were
      tested using ESBL confirmatory tests, PCR and sequencing for CTX-M, AmpC, TEM and
      SHV. The incidence of Enterobacteriaceae producing CTX-M-15 (n = 7), CTX-M-2 (n =
      12), CTX-M-14 (n = 3), CMY-2 (n = 2) or CTX-M-15/2/14 and CMY-2 (n = 4) in bovine
      faeces was 28/897 (3.1%) faecal samples. These genes had spread to Escherichia
      coli (n = 23) and three genera of Enterobacteriaceae (n = 5). Herd prevalence was
      found to be 20/381 (5.2%) dairy farms. The 23 E. coli isolates showed clonal
      diversity, as assessed by multilocus sequence typing and pulsed-field gel
      electrophoresis. The pandemic E. coli strain ST131 producing CTX-M-15 or CTX-M-27
      was not detected. CONCLUSIONS: Three clusters of CTX-M (CTX-M-15, CTX-M-2, CTX-M
      14) had spread among Japanese dairy farms. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first report on the prevalence of multidrug-resistant CTX-M-15
      producing E. coli among Japanese dairy farms.

PMID- 23551816
TI  - Effects of dietary salt intake on renal function: a 2-year study in healthy aged
      cats.
AB  - BACKGROUND: Increasing salt intake to promote diuresis has been suggested in the
      management of feline lower urinary tract disease. However, high dietary salt
      intake might adversely affect blood pressure and renal function. OBJECTIVES: The
      objective of this study was to assess the long-term effects of increased salt
      intake on renal function in healthy aged cats. METHODS: This study was
      controlled, randomized, and blinded. Twenty healthy neutered cats (10.1 +/- 2.4
      years) were randomly allocated into 2 matched groups. One group was fed a high
      salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other a control diet
      of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal
      chloride). Clinical examination, glomerular filtration rate, blood pressure
      measurement, cardiac and kidney ultrasonography, and urinary and blood tests were
      performed before and over 24 months after diet implementation. Statistics were
      performed using a general linear model. RESULTS: Sixteen cats completed the 2
      year study. The only variables affected by dietary salt intake were plasma
      aldosterone and urinary sodium/creatinine ratio, respectively, higher and lower
      in the control group all over the study period and urinary specific gravity,
      lower in the high salt diet group at 3 months. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Glomerular filtration rate (GFR), blood pressure, and other routine
      clinical pathological variables in healthy aged cats were not affected by dietary
      salt content. The results of this 2 year study do not support the suggestion that
      chronic increases in dietary salt intake are harmful to renal function in older
      cats.

PMID- 23551818
TI  - Esophageal bezoar in the setting of achalasia.

PMID- 23551817
TI  - Plastic damage induced fracture behaviors of dental ceramic layer structures
      subjected to monotonic load.
AB  - PURPOSE: The aim of this study was to compare failure modes and fracture strength
      of ceramic structures using a combination of experimental and numerical methods.
      MATERIALS AND METHODS: Twelve specimens with flat layer structures were
      fabricated from two types of ceramic systems (IPS e.max ceram/e.max press-CP and
      Vita VM9/Lava zirconia-VZ) and subjected to monotonic load to fracture with a
      tungsten carbide sphere. Digital image correlation (DIC) and fractography
      technology were used to analyze fracture behaviors of specimens. Numerical
      simulation was also applied to analyze the stress distribution in these two types
      of dental ceramics. RESULTS: Quasi-plastic damage occurred beneath the indenter
      in porcelain in all cases. In general, the fracture strength of VZ specimens was
      greater than that of CP specimens. The crack initiation loads of VZ and CP were
      determined as 958 +/- 50 N and 724 +/- 36 N, respectively. Cracks were induced by
      plastic damage and were subsequently driven by tensile stress at the
      elastic/plastic boundary and extended downward toward to the veneer/core
      interface from the observation of DIC at the specimen surface. Cracks penetrated
      into e.max press core, which led to a serious bulk fracture in CP crowns, while
      in VZ specimens, cracks were deflected and extended along the porcelain/zirconia
      core interface without penetration into the zirconia core. The rupture loads for
      VZ and CP ceramics were determined as 1150 +/- 170 N and 857 +/- 66 N,
      respectively. CONCLUSIONS: Quasi-plastic deformation (damage) is responsible for
      crack initiation within porcelain in both types of crowns. Due to the intrinsic
      mechanical properties, the fracture behaviors of these two types of ceramics are
      different. The zirconia core with high strength and high elastic modulus has
      better resistance to fracture than the e.max core.

PMID- 23551819
TI  - Calciphylaxis and sodium thiosulphate: a glimmer of hope in desperate situation.
AB  - BACKGROUND: Calciphylaxis is an uncommon and often under diagnosed condition
      affecting patients undergoing chronic dialysis. Its pathogenesis is poorly
      understood. The abnormalities of calcium, phosphate and parathyroid hormone
      homeostasis leading to vascular calcification and ischaemic skin necrosis are
      thought to be the central problem. Meticulous wound care and aggressive metabolic
      control remain the cornerstone of the treatment; however, the overall benefit of
      these treatment options remains low and mortality and morbidity remain very high.
      Sodium thiosulphate is an inorganic salt, which is used for treating acute
      cyanide poisoning, recurrent calcium urolithiasis and nephrocalcinosis. Recently,
      it has also been reported to be useful in treating severe cases of calciphylaxis
      with promising results. METHODS: A resistant case of calciphylaxis in a patient
      on long-term haemodialysis was treated with sodium thiosulphate (50 ml solution
      with 50% sodium thiosulphate) three times a week during the end of each dialysis
      session. RESULTS: The skin lesions started to heal after two weeks and completely
      resolved after five months of treatment. CONCLUSIONS: Sodium thiosulphate can be
      a safe and effective treatment option for resistant and severe cases of
      calciphylaxis.

PMID- 23551820
TI  - Who are our readers?

PMID- 23551821
TI  - The delta subfamily of glutamate receptors: characterization of receptor chimeras
      and mutants.
AB  - The delta receptors, GluD1 and GluD2, are regarded as a subfamily of the
      ionotropic glutamate receptors solely because of sequence homology. While they
      play important roles in cerebellar function and high-frequency hearing and appear
      to serve structural functions at synapses, ligand-gated ion channel function has
      not been observed. However, we have previously shown that GluD2 can form
      functional ion channels when grafted with the ligand binding domain of a kainate
      receptor. In this study, we characterized this chimera as well as additional rat
      delta receptor chimeras and point mutants in more detail. We found that the
      kainate receptor ligand binding domain renders GluD1 functional as well, and
      GluD2 becomes a functional ion channel also when provided with an AMPA receptor
      ligand binding domain. Point mutations indicate that the GluD2 ion pore operates
      similarly but not identically to that of AMPA (alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid) and kainate receptors. GluD2 mutated at a
      conserved arginine within the linker region connecting the ligand binding domain
      to the ion pore domain displays spontaneous currents that occur in the absence of
      agonists and are inhibited by agonist application - a behavior reminiscent of
      that of the previously characterized lurcher mutant. Using our chimeric approach,
      we provide evidence that this inhibition of spontaneous currents by agonists may
      be caused by desensitization. Our results show that delta receptors have
      functional gating machineries and ion permeation pathways similar but not
      identical to those of AMPA and kainate receptors, while the key differences seem
      to be located within the ligand binding domain.

PMID- 23551822
TI  - Blood alcohol concentration as a determinant of outcomes after traumatic spinal
      cord injury.
AB  - BACKGROUND: Pre-clinical studies indicate a potential detrimental effect of
      ethanol on tissue sparing and locomotor recovery in animal models of spinal cord
      injury (SCI). Given this, an examination of whether blood alcohol concentration
      (BAC) is a potential determinant of survival and neurological and functional
      recovery after acute traumatic SCI was carried out. METHODS: All patients who
      were enrolled in the Third National Spinal Cord Injury Study (NASCIS-3) were
      included. The study population was divided into 'non-alcohol' (BAC equal to
      00/00), 'legal' (BAC greater than 0 up to 0.80/00) and 'illegal' (BAC greater
      than 0.80/00) subgroups. Outcome measures included survival, NASCIS motor and
      sensory scores, NASCIS pain scores and Functional Independence Measure (FIM)
      determinants at baseline and at 6 weeks, 6 months and 1 year post-SCI. Analyses
      were adjusted for major potential confounders: age, sex, ethnicity, trial
      protocol, Glasgow coma score, and cause, level and severity of SCI. RESULTS:
      Among 499 patients (423 males and 76 females; ages from 14 to 92 years), the mean
      BAC was 0.054 +/- 0.0060/00 (range 0-1). The survival at 1 year (94.4%) was not
      associated with the BAC (P = 0.374). Moreover, BAC was not significantly
      correlated with motor recovery (P > 0.166), sensory recovery (P > 0.323), change
      in pain score (P > 0.312) or functional recovery (P > 0.133) at 6 weeks, 6 months
      and 1 year post-SCI. CONCLUSIONS: Our results, for the first time, show that the
      BAC at emergency admission does not adversely affect the patients' mortality,
      neurological impairment or functional disability over the course of the first
      year after SCI.

PMID- 23551823
TI  - Posterior reversible encephalopathy syndrome following a scorpion sting.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity
      not yet understood, that is present with transient neurologic symptoms and
      particular radiological findings. The most common imaging pattern in PRES is the
      presence of edema in the white matter of the posterior portions of both cerebral
      hemispheres. The cause of PRES is unclear. We report a case of 13-year-old male
      who was stung by a scorpion and developed a severe headache, visual disturbance,
      and seizures and had the diagnosis of PRES with a good outcome. Numerous factors
      can trigger this syndrome, most commonly: acute elevation of blood pressure,
      abnormal renal function, and immunosuppressive therapy. There are many cases
      described showing the relationship between PRES and eclampsia, transplantation,
      neoplasia and chemotherapy treatment, systemic infections, renal disease acute,
      or chronic. However, this is the first case of PRES following a scorpion sting.

PMID- 23551824
TI  - Superficial bacterial pyoderma in cats.

PMID- 23551825
TI  - Solitary fibrous tumor of all sites: outcome of late recurrences in 14 patients.
AB  - BACKGROUND: We explore the pattern of late recurrence (LR) in solitary fibrous
      tumor (SFT), focusing on histopathologic characteristics, clinical presentation
      and patients (pts) outcome. METHODS: Clinical records of all pts with confirmed
      pathologic diagnosis of SFT treated at our Institution from 2005 to 2011 were
      reviewed. We analysed the data of pts who relapsed >=10 years after initial
      diagnosis. RESULTS: A total of 14 pts were identified. The primary site of origin
      was pleura (5 pts), pelvis (4 pts), head and neck (3 pts) and retroperitoneum (2
      pts). Primary tumor was a typical SFT in 5 and a malignant SFT in 7 out of 12 pts
      whose tumor tissue was available for revision. The median time to first
      recurrence was 12 years (range 10-23). The first relapse was local in 11 cases,
      distant in 3. Five pts later developed distant metastases. Four out of 5 cases of
      typical SFT developed distant metastases in spite of their initial benign aspect.
      No patient was disease-free at the time of the analyses. CONCLUSION: Our series
      suggests that LR can occur in SFT and some cases can behave aggressively even in
      the absence of any primary morphologic evidence of malignancy. A prolonged follow
      up may be advisable.

PMID- 23551826
TI  - Pleasure and pain: the effect of (almost) having an orgasm on genital and
      nongenital sensitivity.
AB  - INTRODUCTION: The effect of sexual arousal and orgasm on genital sensitivity has
      received little research attention, and no study has assessed sensation
      pleasurableness as well as painfulness. AIM: To clarify the relationship between
      sexual arousal, orgasm, and sensitivity in a healthy female sample. METHODS:
      Twenty-six women privately masturbated to orgasm and almost to orgasm at two
      separate sessions, during which standardized pressure stimulation was applied to
      the glans clitoris, vulvar vestibule, and volar forearm at three testing times:
      (i) baseline; (ii) immediately following masturbation; and (iii) following a
      subsequent 15-minute rest period. MAIN OUTCOME MEASURES: Touch thresholds
      (tactile detection sensitivity), sensation pleasurableness ratings (pleasurable
      sensitivity), and pain thresholds (pain sensitivity). RESULTS: Pleasurableness
      ratings were higher on the glans clitoris than the vulvar vestibule, and at most
      testing times on the vulvar vestibule than the volar forearm; and at baseline and
      immediately after masturbation than 15 minutes later, mainly on the genital
      locations only. Pain thresholds were lower on the genital locations than the
      volar forearm, and immediately and 15 minutes after masturbation than at
      baseline. After orgasm, genital pleasurableness ratings and vulvar vestibular
      pain thresholds were lower than after masturbation almost to orgasm. Post
      masturbation pleasurableness ratings were positively correlated with pain
      thresholds but only on the glans clitoris. Hormonal contraception users had lower
      pleasurableness ratings and pain thresholds on all locations than nonusers. There
      were no significant effects for touch thresholds. CONCLUSIONS: Masturbation
      appears to maintain pleasurable genital sensitivity but increase pain
      sensitivity, with lower genital pleasurable sensitivity and higher vulvar
      vestibular pain sensitivity when orgasm occurs. Findings suggest that enhancing
      stimulation pleasurableness, psychological sexual arousal and lubrication
      mitigate normative increases in pain sensitivity during sexual activity, and
      underscore the importance of measuring both pleasure and pain in sensation
      research.

PMID- 23551827
TI  - Postoperative administration of dienogest plus estradiol valerate versus
      levonorgestrel-releasing intrauterine device for prevention of pain relapse and
      disease recurrence in endometriosis patients.
AB  - AIM: In recent years, both dienogest, a fourth-generation progestin, and
      levonorgestrel-releasing intrauterine device have been found to be effective in
      terms of endometriosis-related pelvic pain improvement. No data, however, are
      available about their efficacy in terms of postoperative recurrence prevention in
      women recently submitted to surgery for endometriosis at every stage. Our
      objective was to compare two postoperative medical approaches for pain control
      and reduction of recurrences in patients undergoing surgery for endometriosis.
      MATERIAL AND METHODS: Ninety-two patients undergoing surgery for endometriosis
      and subsequent treatment by estradiol valerate + dienogest (EP) (group A) or
      levonorgestrel-releasing uterine device (LNG-IUD) (Group B) between January 2009
      and June 2010 were retrospectively analyzed. The primary endpoints were pain
      relapse and disease recurrence rate at 12 and 24 months. The secondary endpoint
      was patient satisfaction with the therapy at 24 months. RESULTS: Forty-eight
      patients in Group A and 44 in Group B were examined. At 12 and 24 months a
      statistically greater reduction both in Ca125 levels and VAS score was seen in
      women treated with EP compared to LNG-IUD. The recurrence rate at 12 and 24
      months follow-up was slightly lower, but not at a significant level, in Group A
      than in Group B. Finally, satisfaction with treatment at 24 months was
      significantly higher in Group B. CONCLUSION: EP administration is significantly
      more effective than LNG-IUD in reducing pelvic pain and more effective in
      reducing recurrence rate but not at a significant level. LNG-IUD, however, has
      significantly higher patient satisfaction.

PMID- 23551828
TI  - Drug use evaluation of cefepime in the first affiliated hospital of Bengbu
      medical college: a retrospective and prospective analysis.
AB  - BACKGROUND: Cefepime is a fourth generation cephalosporin antimicrobial. Its
      extended antimicrobial activity and infrequent tendency to engender resistance
      make it popular for the treatment of infections. However, proper use of cefepime
      has not been studied adequately. In this study, we used a retrospective cohort
      and a prospective cohort to evaluate the usage pattern, adverse effects and cost
      effectiveness of cefepime by conducting a drug use evaluation (DUE) program in
      the First Affiliated Hospital of Bengbu Medical College, Anhui, China. METHODS:
      The DUE criteria for cefepime were established by applying literature review and
      expert consultation, an effective method to promote interventions that will
      improve patient outcomes and the cost-effectiveness of drug therapy. According to
      the criteria, we performed a cross-sectional retrospective (cycle A) study on 96
      hospitalized patients who received cefepime treatment and a prospective (cycle B)
      study on 111 hospitalized patients with cefepime treatment intervention. After
      identifying problems with usage and completing a cefepime use evaluation for
      cycle A, 2 months of educational intervention among professionals were given and
      a more effective and rational system of cefepime use was set up. During the 2
      months, the lectures were arranged and attendance of prescribers was required.
      RESULTS: The data from cycle A showed that the biggest problem was irrational
      prescription of cefepime; bacterial culture and drug sensitivity tests for
      cefepime were also not carried out. Following 2 months of educational
      intervention among professionals, the results for cycle B showed that the correct
      indication rate was 94.59%, compared with 84.38% in cycle A. Use of bacterial
      culture and sensitivity tests also improved, by 88.29% in cycle B compared with
      65.22% in cycle A. Compared with cycle A, the significantly improved items (P <
      0.05) in cycle B were blood examination, liver function monitoring, renal
      function monitoring, dose and duration, dosing frequency and correct medication
      combinations. CONCLUSIONS: Cefepime can be used appropriately for the right
      indications and in a cost-effective way for the majority of patients through
      educational intervention, including the special precautions that must be followed
      for appropriate dosing frequency and duration. DUE programs will become one model
      of hospital pharmacy care and part of the plan for continuous improvements to the
      quality of health care in China.

PMID- 23551829
TI  - Relationship between nine haloacetic acids with total organic halogens in
      different experimental conditions.
AB  - The effects of pH and bromide ion concentration on the formation of nine
      haloacetic acids (HAAs) and total organic halogens (TOX) in chlorinated drinking
      water have been evaluated. In an extensive study, the relationships of nine HAAs
      with TOX have been investigated. Honesty Significant Differences test (HSD) and
      ANOVA tests were used for the statistical analyses. The study determined the
      concentration range of nine HAAs as of a percentage of TOX at varying
      experimental conditions. Statistical analyses showed that the parameters pH and
      Br had significant effects on the formation of nine HAAs and TOX. This study also
      showed that brominated and mixed species of HAAs would be dominant in the
      presence of high bromide ion concentration which contributes a high percentage of
      the TOX. The results of this study could be used to set up a maximum contaminant
      level of TOX as a water quality standard for chlorination by-products. 

PMID- 23551830
TI  - The lumazine synthase/riboflavin synthase complex: shapes and functions of a
      highly variable enzyme system.
AB  - The xylene ring of riboflavin (vitamin B2 ) is assembled from two molecules of
      3,4-dihydroxy-2-butanone 4-phosphate by a mechanistically complex process that is
      jointly catalyzed by lumazine synthase and riboflavin synthase. In Bacillaceae,
      these enzymes form a structurally unique complex comprising an icosahedral shell
      of 60 lumazine synthase subunits and a core of three riboflavin synthase
      subunits, whereas many other bacteria have empty lumazine synthase capsids,
      fungi, Archaea and some eubacteria have pentameric lumazine synthases, and the
      riboflavin synthases of Archaea are paralogs of lumazine synthase. The structures
      of the molecular ensembles have been studied in considerable detail by X-ray
      crystallography, X-ray small-angle scattering and electron microscopy. However,
      certain mechanistic aspects remain unknown. Surprisingly, the quaternary
      structure of the icosahedral beta subunit capsids undergoes drastic changes,
      resulting in formation of large, quasi-spherical capsids; this process is
      modulated by sequence mutations. The occurrence of large shells consisting of 180
      or more lumazine synthase subunits has recently generated interest for protein
      engineering topics, particularly the construction of encapsulation systems.

PMID- 23551831
TI  - The combined effects of family size and farm exposure on childhood hay fever and
      atopy.
AB  - BACKGROUND: Exposure to farming environments and siblings is associated with
      reduced risks of childhood hay fever and atopy. We explored the independence and
      interaction of these protective effects in the GABRIELA study. METHODS:
      Questionnaire surveys on farming, asthma, and allergies were conducted in four
      central European areas among 79,888 6-12-yr-old children. Aeroallergen-specific
      serum IgE was measured in a stratified sample of 8,023 children. Multiple
      logistic regression was used to compare gradients in allergy prevalence by
      sibship size across three categories of exposure to farming environments.
      RESULTS: The prevalence of hay fever ranged from 2% (95% confidence interval
      1.6%; 2.7%) among farmers' children with more than two siblings to 12% (11.2%;
      13.0%) among children with no farm exposure and no siblings. Farming families
      were larger on average. More siblings and exposure to farming environments
      independently conferred protection from hay fever and atopy. There was no
      substantial effect modification between family size and exposure to farming
      environments. The odds ratios for hay fever per additional sibling were 0.79
      among unexposed non-farm children, 0.77 among farm-exposed non-farm children, and
      0.72 among children from farming families (2df interaction test: p = 0.41).
      CONCLUSION: The inverse association of exposure to farming environments with hay
      fever is found in all sizes of family, with no substantial tendency to saturation
      or synergism. This suggests that different biological mechanisms may underlie
      these two protective factors. Combinations of a large family and exposure to
      farming environments markedly reduce the prevalence of hay fever and indicate the
      strength of its environmental determinants.

PMID- 23551832
TI  - Synthetic epidermoid cyst simulation.

PMID- 23551833
TI  - Nucleoporin Nup188 is required for chromosome alignment in mitosis.
AB  - Most cancer cells are aneuploid, which could be caused by defects in chromosome
      segregation machinery. Nucleoporins (Nup) are components of the nuclear pore
      complex, which is essential for nuclear transport during interphase, but several
      nucleoporins are also known to be involved in chromosome segregation. Here we
      report a novel function of Nup188, one of the nucleoporins regulating chromosome
      segregation. Nup188 localizes to spindle poles during mitosis, through the C
      terminal region of Nup188. In Nup188-depleted mitotic cells, chromosomes fail to
      align to the metaphase plate, which causes mitotic arrest due to the spindle
      assembly checkpoint. Both the middle and the C-terminal regions were required for
      chromosome alignment. Robust K-fibers, microtubule bundles attaching to
      kinetochores, were hardly formed in Nup188-depleted cells. Significantly, we
      found that Nup188 interacts with NuMA, which plays an instrumental role in
      focusing microtubules at centrosomes, and NuMA localization to spindle poles is
      perturbed in Nup188-depleted cells. These data suggest that Nup188 promotes
      chromosome alignment through K-fiber formation and recruitment of NuMA to spindle
      poles. 

PMID- 23551834
TI  - C9ORF72 expansion in a family with bipolar disorder.
AB  - OBJECTIVE: To investigate the role in bipolar disorder of the C9ORF72
      hexanucleotide repeat expansion responsible for frontotemporal lobe dementia and
      amyotrophic lateral sclerosis. METHODS: Eighty-nine subjects from a previously
      described panel of individuals with bipolar disorder ascertained for genetic
      studies were screened to detect expansion of the C9ORF72 repeat. One two
      generation family with bipolar disorder and an expanded repeat was characterized
      in depth using molecular diagnostics, imaging, histopathology, and neurological
      and neuropsychological evaluation. RESULTS: One proband, with the typical
      clinical presentation of bipolar disorder, carried an expanded C9ORF72 allele of
      heterogeneous length between 14 and 20 kilobases (kb) as assessed by Southern
      blot. The expanded allele was inherited from a parent with atypical, late onset
      clinical features of bipolar disorder, who subsequently progressed to
      frontotemporal lobe dementia. The expansion in peripheral blood of the parent
      ranged from 8.5 to 20 kb. Cultured lymphoblastoid cells from this parent
      exhibited a homogeneous expansion of only 8.5 kb. CONCLUSIONS: The disease course
      in the two generations described here demonstrates that expansion of the C9ORF72
      may be associated with a form of bipolar disorder that presents clinically with
      classic phenomenology and progression to neurodegenerative disease. The frequency
      in our bipolar disorder cohort was only 1%, indicating that C9ORF72 is not a
      major contributor to bipolar disorder. DNA from cultured cells may be biased
      towards shorter repeats and nonrepresentative of the endogenous C9ORF72
      expansion.

PMID- 23551835
TI  - Comparative in vitro fungicidal activity of echinocandins against Candida
      albicans in peritoneal dialysis fluids.
AB  - The peritoneal dialysis (PD)-associated peritonitis caused by fungi is a
      relatively rare, but very serious disease. PD fluids (PDFs) affect inhibitory
      efficacy on the microorganisms' growth, which may compromise the affectivity of
      some antimicrobials. The purpose of this study was to investigate in vitro the
      fungicidal effectiveness of echinocandins in diverse PDFs. The fungicidal
      efficacy of caspofungin (CAS), anidulafungin (ANA), micafungin (MYC) against five
      clinical isolates of Candida albicans was studied in the different PDFs using
      time-kill curves. As control substance amphotericin B was used. Echinocandins
      showed slower and reduced killing of C. albicans in PDFs when compared with the
      time-kill curves in control bouillon. At concentration of 8 * minimal inhibitory
      concentration (MIC) the greatest reduction in the growth of C. albicans was seen
      by ANA in lactate-buffered Nutrineal PD4((r)) with 1.1% amino acid (2.33 +/- 0.52
      log10 CFU ml(-1) ), and by CAS and MYC in lactate-buffered Dianeal PD4((r)) with
      1.36% glucose (2.36 +/- 0.89 log10 CFU ml(-1) and 2.36 +/- 0.99 log10 CFU ml(-1)
      respectively). Using high concentration of 128 * MIC echinocandins achieved
      fungicidal effect in all PDFs. PDFs may significantly impair the activities of
      echinocandins, but fungicidal activity of drugs can be achieved at high
      concentration of 128 * MIC.

PMID- 23551836
TI  - Patient and health-care impact of a pilot rheumatic heart disease screening
      program.
AB  - AIM: The aim of this study was to assess the impact of a pilot screening program
      for rheumatic heart disease (RHD) on patient quality of life (QOL) and health
      services. METHODS: A QOL questionnaire (CHQ-PF28) was used to assess the impact
      of RHD screening on children with a potentially abnormal screening echocardiogram
      and matched normal controls. The health service response to a potentially
      abnormal screening echocardiogram and the impact of the screening program on
      health services was evaluated using medical record review, carer interviews and
      surveys of health-care providers. RESULTS: QOL was assessed in 68 children.
      Potentially abnormal screening echocardiograms were associated with poorer QOL in
      the General Health Perception (P < 0.05) and Parental Impact - Emotional (P <
      0.05) domains. Health services contacted 82% of children with potentially
      abnormal echocardiograms, and clinical review occurred in 56%. A potentially
      abnormal echocardiogram was associated with a change in management in 6% (2/34)
      of children. When surveyed, 49% of health providers were aware of the RHD
      screening program, 29% had seen children referred with screening abnormalities
      and 85% of these providers stated this had an impact on local health-care
      delivery. CONCLUSIONS: This pilot RHD screening program was associated with
      poorer child and carer QOL for those with potentially abnormal results, greater
      health provider workload and suboptimal clinical follow-up. The adoption of
      screening for RHD in high-risk populations should be approached cautiously.
      Further research is required to facilitate and validate improved
      echocardiographic diagnostic criteria for RHD and the systematic assessment of
      the benefits and adverse effects of such screening.

PMID- 23551837
TI  - The sweets standing at the borderline between allo- and xenotransplantation.
AB  - Animal cells are densely covered with glycoconjugates, such as N-glycan, O
      glycan, and glycosphingolipids, which are important for various biological and
      immunological events at the cell surface and in the extracellular matrix.
      Endothelial alpha-Gal carbohydrate epitopes (Galalpha3Gal-R) expressed on porcine
      tissue or cell surfaces are such glycoconjugates and directly mediate hyperacute
      immunological rejection in pig-to-human xenotransplantation. Although researchers
      have been able to develop alpha1,3-galactosyltransferase (GalT) gene knockout
      (KO) pigs, there remain unclarified non-Gal antigens that prevent
      xenotransplantation. Based on our expertise in the structural analysis of
      xenoantigenic carbohydrates, we describe the immunologically significant non
      human carbohydrate antigens, including alpha-Gal antigens, analyzed as part of
      efforts to assess the antigens responsible for hyperacute immunological rejection
      in pig-to-human xenotransplantation. The importance of studying human, pig, and
      GalT-KO pig glycoprofiles, and of developing adequate pig-to-human glycan
      databases, is also discussed. 

PMID- 23551838
TI  - Patterns of care and outcomes of radiotherapy for lymph node positivity after
      radical prostatectomy.
AB  - OBJECTIVE: To evaluate the use and outcomes of adjuvant radiation therapy (ART)
      for men with lymph node (LN)-positive disease after radical prostatectomy (RP)
      using a population-based approach. PATIENTS AND METHODS: Surveillance,
      Epidemiology, and End Results (SEER)-Medicare linked data from 1995 to 2007 was
      used to identify 577 men with LN metastases discovered during RP and absence of
      distant metastases, of which 177 underwent ART <=1 year of RP. Propensity score
      models were used to compare overall mortality and prostate cancer-specific
      mortality (PCSM) for men that did and those that did not receive ART. RESULTS:
      Men in both groups received adjuvant androgen-deprivation therapy at similar
      rates after propensity weighting adjustments (33.6% vs 33.7%, P = 0.977). ART was
      not associated with differences in overall (5.09 vs 3.77 events per 100 person
      years, P = 0.153) or PCSM (2.89 vs 1.31, P = 0.090) relative to men who did not
      receive ART. CONCLUSIONS: ART after RP in men with LN-positive prostate cancer
      was not associated with improved overall or disease-specific survival, in
      contrast to previous single-centre studies. Prospective randomised studies are
      needed to assess the effectiveness of ART in this patient population.

PMID- 23551839
TI  - Postextrasystolic potentiation in low-gradient, severe aortic stenosis: a poor
      man's stress echo?
AB  - An elderly man with dyspnea and syncope was found to have severe aortic stenosis
      (AS) by the continuity equation, despite a transaortic gradient that was only
      moderately elevated, in the setting of severe left ventricular dysfunction. The
      transaortic gradient increased during postextrasystolic beats, suggesting that
      his that his AS was truly severe; this was confirmed by dobutamine
      echocardiography. He underwent transcatheter aortic-valve replacement (TAVR),
      with subsequent improvement in left ventricular systolic function. The diagnostic
      and prognostic significance of postextrasystolic potentiation, with associated
      increase in aortic stenosis gradient, deserves renewed attention in the TAVR era.

PMID- 23551840
TI  - Cardiac troponin-I concentration, myocardial arteriosclerosis, and fibrosis in
      dogs with congestive heart failure because of myxomatous mitral valve disease.
AB  - BACKGROUND: Few previous studies have investigated the association between
      biomarkers and cardiac disease findings in dogs with naturally occurring
      myxomatous mitral valve disease (MMVD). AIM: To investigate if histopathological
      changes at necropsy could be reflected by in vivo circulating concentrations of
      cTnI and aldosterone, and renin activity, in dogs with naturally occurring
      congestive heart failure because of MMVD. ANIMALS: Fifty privately owned dogs
      with MMVD and heart failure. METHODS: Longitudinal Study. Dogs were prospectively
      recruited and examined by clinical and echocardiographical examination twice
      yearly until time of death. Blood was stored for batched analysis of
      concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a
      standardized necropsy protocol. RESULTS: cTnI were associated with
      echocardiographic left ventricular end-diastolic dimension (P < .0001) and
      proximal isovolumetric surface area radius (P < .004). Furthermore, in vivo cTnI
      concentrations reflected postmortem findings of global myocardial fibrosis (P <
      .001), fibrosis in the papillary muscles (P < .001), and degree of arterial
      luminal narrowing (P < .001) Aldosterone or renin activity did not reflect any of
      the cardiac disease variables investigated. CONCLUSION AND CLINICAL IMPORTANCE:
      Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by
      circulating cTnI concentration, but not by aldosterone concentration or renin
      activity. Cardiac troponin I could be a valuable biomarker for myocardial
      fibrosis in dogs with chronic cardiac diseases.

PMID- 23551841
TI  - Identification of echinoderms (Echinodermata) from an anchialine cave in Cozumel
      Island, Mexico, using DNA barcodes.
AB  - The echinoderm species richness of the Aerolito de Paraiso anchialine cave, on
      Cozumel Island, in the Mexican Caribbean, is assessed on the basis of
      morphological and DNA barcoding data. We included specimens from this cave system
      and from different open sea areas, and employed two different approaches for
      species delineation based on DNA barcoding data: a 2% cox1 divergence and the
      general mixed Yule-coalescent (GMYC) approaches. We subsequently compared the
      results derived from these approaches with our morphospecies discrimination. A
      total of 188 cox1 sequences belonging to specimens of four echinoderm classes
      were examined. The 2% cox1 divergence and GMYC approaches recovered 78 and 70
      putative species, respectively, 24 and 22 of which corresponded to specimens from
      the anchialine system. Of 26 echinoderm species identified in the cave system,
      seven appear to be endemic to it. Among these are Copidaster carvenicola Solis
      Marin & Laguarda-Figueras, 2010, two morphologically distinctive, undescribed
      species belonging to Asterinides and Ophionereis and four probably cryptic
      undescribed species originally assigned to Amphipholis squamata (Delle Chiaje,
      1839), Astropecten duplicatus Gray, 1840, Copidaster lymani (AH Clark, 1948) and
      Ophiothrix angulata (Say, 1825). Further research and protection of this
      particularly fragile ecosystem becomes urgent because construction of tourism
      developments is planned nearby. 

PMID- 23551843
TI  - Closed hollow bulb obturator--one-step fabrication: a clinical report.
AB  - A method is described for the fabrication of a closed hollow bulb obturator
      prosthesis using a hard thermoforming splint material and heat-cured acrylic
      resin. The technique allowed the thickness of the thermoformed bulb to be
      optimized for weight reduction, while the autopolymerized seal area was covered
      in heat-cured acrylic resin, thus eliminating potential leakage and
      discoloration. This technique permits the obturator prosthesis to be processed to
      completion from the wax trial denture without additional laboratory investing,
      flasking, and processing. 

PMID- 23551845
TI  - Intra-operative microwave ablation of liver malignancies with tumour permittivity
      feedback control: a prospective ablate and resect study.
AB  - BACKGROUND: Tumour permittivity feedback control is a novel method for microwave
      ablation (MWA) that theoretically allows for larger, more predictable ablations.
      This prospective case series evaluates the feasibility and efficacy of MWA of
      liver malignancies using a device with tumour permittivity feedback control.
      METHODS: Ten consecutive patients initially determined to be candidates for
      surgical resection of a liver malignancy underwent intra-operative MWA with
      tumour permittivity feedback control followed by a surgical resection. A 14-gauge
      Medwaves microwave antenna was used to deliver a single treatment according to
      the manufacturer's recommendations. Tumours were assessed grossly as well as by
      haematoxylin and eosin (H&E) and tetrazolium chloride staining. The primary end
      point was per cent tumour necrosis. RESULTS: The median maximum ablation diameter
      measured was 4.1 cm (range 3.0-6.8). The median ablation volume was 8.7 cm(3)
      (range 4.84-17.55). Six of the 10 tumours demonstrated a pathological complete
      response (CR). Six of seven tumours <= 3 cm demonstrated a pathological CR. Zero
      of the three tumours >= 3 cm had a pathological CR, but all had >= 50% tumour
      necrosis. All patients survived and there were no ablation-related morbidities.
      DISCUSSION: MWA of liver tumours with tumour permittivity feedback control is
      feasible and appears effective for the treatment of small (< 3 cm) liver tumours.

PMID- 23551844
TI  - Neuroimaging of brain changes associated with cognitive impairment in Parkinson's
      disease.
AB  - Cognitive impairment occurs frequently in Parkinson's disease (PD) and the
      concept of Mild Cognitive Impairment in PD (PD-MCI) has recently emerged.
      Patients with mild impairment are at risk of developing dementia, and thus it is
      a topic of growing interest. Many previous studies have investigated the neural
      correlates of cognitive impairment, in particular executive dysfunction, in PD
      patients without dementia using neuroimaging techniques including structural MRI,
      functional MRI and PET imaging. These studies, which have provided a foundation
      for understanding which brain regions and neurotransmitter systems may be
      involved in executive dysfunction in PD, will be reviewed. Recent neuroimaging
      studies that have used specific criteria to classify patients as PD-MCI, in the
      hopes of gaining further insight into the underlying neural mechanisms will also
      be discussed. In particular, this review will cover key findings involving
      structural MRI investigating grey and white matter changes, functional MRI to
      examine changes in neural activation and PET imaging to investigate metabolic and
      neurochemical changes that have led to an improved understanding of pathology
      associated with executive dysfunction in PD without dementia and PD-MCI. 

PMID- 23551846
TI  - Sequence type 398 meticillin-resistant Staphylococcus aureus infection in a pet
      rabbit.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is a frequent
      pathogen of humans and many animal species, and has become established as a
      veterinary pathogen. CASE REPORT: In this case report we describe an MRSA
      infection in a dwarf rabbit, treatment of the infection and, subsequently, the
      genetic analysis of the isolated strain. The pet rabbit was presented to an
      animal hospital due to recurrent swellings on the head and on the neck.
      Bacteriological examination yielded Staphylococcus aureus, which was resistant to
      beta-lactam antibiotics. The isolate was confirmed as an MRSA by mecA PCR, Panton
      Valentine leukocidin (PVL) negative, and typed as multilocus sequence type
      (ST)398/staphylococcal protein A (spa) type t011/staphylococcal cassette
      chromosome mec (SCCmec) type SCCmecIVa. The rabbit was treated with rifampicin
      for 2 weeks. After 2.5 weeks the rabbit was clinically normal and control swabs
      were negative for MRSA. CONCLUSIONS AND CLINICAL IMPORTANCE: This study is the
      first to report MRSA in a rabbit in Austria. This study contributes to the
      growing evidence that MRSA ST398 could be isolated from a variety of animals.

PMID- 23551847
TI  - Variations in catheter-related bloodstream infections rates based on local
      practices.
AB  - BACKGROUND: Catheter-related bloodstream infection (CRBSI) surveillance serves as
      a quality improvement measure that is often used to assess performance. We
      reviewed the total number of microbiological samples collected in three Belgian
      intensive care units (ICU) in 2009-2010, and we described variations in CRBSI
      rates based on two factors: microbiological documentation rate and CRBSI
      definition which includes clinical criterion for coagulase-negative
      Staphylococcus (CNS) episode. FINDINGS: CRBSI rates were 2.95, 1.13 and 1.26 per
      1,000 estimated catheter-days in ICUs A, B and C, respectively. ICU B cultured
      fewer microbiological samples and reported the lowest CRBSI rate. ICU C had the
      highest documentation rate but was assisted by support available from the
      laboratory for processing single CNS positive blood cultures. With the exclusion
      of clinical criterion, CRBSI rates would be reduced by 19%, 45% and 0% in ICUs A,
      B and C, respectively. CONCLUSION: CRBSI rates may be biased by differences of
      blood culture sampling and CRBSI definition. These observations suggest that
      comparisons of CRBSI rates in different ICUs remain difficult to interpret
      without knowledge of local practices.

PMID- 23551848
TI  - Comparison of time series models for predicting campylobacteriosis risk in New
      Zealand.
AB  - Predicting campylobacteriosis cases is a matter of considerable concern in New
      Zealand, after the number of the notified cases was the highest among the
      developed countries in 2006. Thus, there is a need to develop a model or a tool
      to predict accurately the number of campylobacteriosis cases as the Microbial
      Risk Assessment Model used to predict the number of campylobacteriosis cases
      failed to predict accurately the number of actual cases. We explore the
      appropriateness of classical time series modelling approaches for predicting
      campylobacteriosis. Finding the most appropriate time series model for New
      Zealand data has additional practical considerations given a possible structural
      change, that is, a specific and sudden change in response to the implemented
      interventions. A univariate methodological approach was used to predict monthly
      disease cases using New Zealand surveillance data of campylobacteriosis incidence
      from 1998 to 2009. The data from the years 1998 to 2008 were used to model the
      time series with the year 2009 held out of the data set for model validation. The
      best two models were then fitted to the full 1998-2009 data and used to predict
      for each month of 2010. The Holt-Winters (multiplicative) and ARIMA (additive)
      intervention models were considered the best models for predicting
      campylobacteriosis in New Zealand. It was noticed that the prediction by an
      additive ARIMA with intervention was slightly better than the prediction by a
      Holt-Winter multiplicative method for the annual total in year 2010, the former
      predicting only 23 cases less than the actual reported cases. It is confirmed
      that classical time series techniques such as ARIMA with intervention and Holt
      Winters can provide a good prediction performance for campylobacteriosis risk in
      New Zealand. The results reported by this study are useful to the New Zealand
      Health and Safety Authority's efforts in addressing the problem of the
      campylobacteriosis epidemic. 

PMID- 23551850
TI  - Agent-based modeling of competence phenotype switching in Bacillus subtilis.
AB  - BACKGROUND: It is a fascinating phenomenon that in genetically identical bacteria
      populations of Bacillus subtilis, a distinct DNA uptake phenotype called the
      competence phenotype may emerge in 10-20% of the population. Many aspects of the
      phenomenon are believed to be due to the variable expression of critical genes: a
      stochastic occurrence termed "noise" which has made the phenomenon difficult to
      examine directly by lab experimentation. METHODS: To capture and model noise in
      this system and further understand the emergence of competence both at the
      intracellular and culture levels in B. subtilis, we developed a novel multi
      scale, agent-based model. At the intracellular level, our model recreates the
      regulatory network involved in the competence phenotype. At the culture level, we
      simulated growth conditions, with our multi-scale model providing feedback
      between the two levels. RESULTS: Our model predicted three potential sources of
      genetic "noise". First, the random spatial arrangement of molecules may influence
      the manifestation of the competence phenotype. In addition, the evidence suggests
      that there may be a type of epigenetic heritability to the emergence of
      competence, influenced by the molecular concentrations of key competence
      molecules inherited through cell division. Finally, the emergence of competence
      during the stationary phase may in part be due to the dilution effect of cell
      division upon protein concentrations. CONCLUSIONS: The competence phenotype was
      easily translated into an agent-based model - one with the ability to illuminate
      complex cell behavior. Models such as the one described in this paper can
      simulate cell behavior that is otherwise unobservable in vivo, highlighting their
      potential usefulness as research tools.

PMID- 23551851
TI  - Under-reporting of drug use among individuals with schizophrenia: prevalence and
      predictors.
AB  - BACKGROUND: Illicit drug use is common in individuals with schizophrenia, and it
      has been suspected that many individuals under-report their use of substances,
      leading to significant barriers to treatment. This study sought to examine the
      degree to which individuals with schizophrenia disclose their use of drugs on
      self-rated assessments, compared to laboratory assays, and to determine the
      contributors of under-reported drug use in this population. METHOD: A total of
      1042 individuals with schizophrenia who participated in screening/baseline
      procedures for the Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) completed self-rated assessments of substance use and laboratory drug
      testing. Laboratory tests assayed cannabis, cocaine and methamphetamine use; the
      procedures included radioimmunoassay (RIA) and urine drug screens. RESULTS: A
      significant proportion of participants tested positive for drug use on laboratory
      measures (n = 397; 38%), and more than half (n = 229; 58%) did not report using
      these drugs. Logistic regression models confirmed that patients who were most
      likely to conceal their use tended to be older, and presented with greater
      neurocognitive deficits. Patients who accurately reported drug use tended to have
      greater involvement with the criminal justice system. Illness severity and
      psychopathology were not associated with whether patients disclosed drug use.
      CONCLUSIONS: Rates of under-reported drug use are considerable among individuals
      with schizophrenia when compared to laboratory assays, and the exclusive reliance
      on self-rated assessments should be used with caution. Patients who under-report
      their drug use are more likely to manifest neurocognitive deficits, which could
      be improved by interventions attempting to optimize treatment.

PMID- 23551852
TI  - Stroke care organization overcomes the deleterious 'weekend effect' on 1-month
      stroke mortality: a population-based study.
AB  - BACKGROUND AND PURPOSE: Suffering a stroke during the weekend is associated with
      a poorer prognosis. The impact of implementing a dedicated stroke care network in
      Dijon, France, in 2003 on 30-day mortality in strokes/transient ischaemic attacks
      (TIA) occurring during weekends/bank holidays was evaluated. METHODS: All cases
      of stroke and TIA from 1985 to 2010 were identified from a population-based
      registry, using multiple overlapping sources of information. Demographics and
      clinical data were recorded. Cox regression models were used to evaluate
      associations between day of onset (weekdays versus weekends/bank holidays) and 30
      day all-cause mortality. Data were stratified according to time periods [before
      (1985-2003) and after (2004-2010) implementation of the stroke network] and
      stroke subtypes (ischaemic stroke and intracerebral hemorrhage). RESULTS: Of the
      5864 recorded patients, 1465 (25%) had their event during weekends/bank holidays.
      Patients with stroke/TIA during weekdays were comparable with those with
      stroke/TIA during weekends/bank holidays for baseline characteristics. Excess
      mortality was observed in patients with stroke/TIA during weekends/bank holidays
      during 1985-2003 (18.2% vs. 14.0%, P < 0.01) but not during 2004-2010 (8.4% vs.
      8.3%, P = 0.74). Onset during weekends/bank holidays was associated with a higher
      risk of 30-day mortality during 1985-2003 (adjusted hazard ratio 1.26; 95% CI
      1.06-1.51, P = 0.01), but not during 2004-2010 (adjusted hazard ratio 0.99; 95%
      CI 0.69-1.43, P = 0.97). CONCLUSION: The deleterious effect of weekends/bank
      holidays on early stroke mortality disappeared after the organization of a
      dedicated stroke care network in our community. Our findings provide strong
      support for the implementation of quality improvement initiatives in order to
      attenuate inequalities in the management of stroke patients.

PMID- 23551853
TI  - Efficacy of light-emitting diode photomodulation in reducing erythema after
      fractional carbon dioxide laser resurfacing: a pilot study.
AB  - BACKGROUND: The most common side effects of fractional carbon dioxide (CO2 )
      laser resurfacing are erythema and edema of the treated skin. Light-emitting
      diode (LED) devices have been shown to stimulate fibroblast activity and hasten
      wound healing. The current study was designed to evaluate the efficacy of such
      LED devices in treating post-laser therapy erythema. OBJECTIVES: To evaluate the
      clinical efficacy of LED photomodulation in reducing erythema resulting from
      ablative fractional CO2 laser resurfacing. MATERIALS AND METHODS: Randomly
      selected facial halves of 10 Korean subjects (Fitzpatrick skin type III-IV) were
      treated using a 635-nm wavelength LED array immediately after full-face
      fractional laser skin resurfacing. Each participant was subsequently treated with
      LED daily for the following 7 days. Clinical photographs, subjective physician
      assessment, and chromometer erythema index were used to track the results, with
      clinical improvement assessed using a 5-point grading scale. RESULTS: The
      postlaser erythema resolved faster on the experimental side than the control
      side, with improvements noted according to physician assessment and chromometer
      erythema index. Statistically significant improvements between the two sides were
      first noted on day 4. CONCLUSION: Treatment using a 635-nm-wavelength LED array
      decreases the intensity and duration of post-fractional CO2 laser treatment
      erythema.

PMID- 23551849
TI  - Modulating the endocannabinoid system in human health and disease--successes and
      failures.
AB  - The discovery of the endocannabinoid system, comprising the G-protein coupled
      cannabinoid 1 and 2 receptors (CB1/2), their endogenous lipid ligands or
      endocannabinoids, and synthetic and metabolizing enzymes, has triggered an
      avalanche of experimental studies implicating the endocannabinoid system in a
      growing number of physiological/pathological functions. These studies have also
      suggested that modulating the activity of the endocannabinoid system holds
      therapeutic promise for a broad range of diseases, including neurodegenerative,
      cardiovascular and inflammatory disorders; obesity/metabolic syndrome; cachexia;
      chemotherapy-induced nausea and vomiting; and tissue injury and pain, amongst
      others. However, clinical trials with globally acting CB1 antagonists in
      obesity/metabolic syndrome, and other studies with peripherally-restricted CB1/2
      agonists and inhibitors of the endocannabinoid metabolizing enzyme in pain, have
      introduced unexpected complexities, suggesting that a better understanding of the
      pathophysiological role of the endocannabinoid system is required to devise
      clinically successful treatment strategies.

PMID- 23551854
TI  - Perianeursymal cyst development after endovascular treatment of a ruptured giant
      aneurysm.

PMID- 23551855
TI  - Role of microRNA in the pathogenesis of malignant lymphoma.
AB  - MicroRNA (miRNA) are non-coding regulatory RNA usually consisting of 20-24
      nucleotides. Over the past decade, increases and decreases in miRNA expression
      have been shown to associate with various types of disease, including cancer. The
      first two known miRNA aberrations resulted from altered expression of DLEU2 and
      C13orf25 in hematological malignancies. DLEU2, which encodes miR-15a and miR-16
      1, was discovered from 13q14 deletion in chronic lymphocytic leukemia, while
      C13orf25, which encodes six mature miRNA (miR-17, miR-18, miR-19a, miR-19b, miR
      20a and miR-92a), was identified from 13q31 amplification in aggressive B-cell
      lymphomas. These miRNA were downregulated or upregulated in accordance with
      genomic deletion or amplification, which suggests that they contribute to
      tumorigenesis through altered regulation of target oncogenes or tumor
      suppressors. Consistent with that idea, miR-15a/16-1 is known to regulate Bcl2 in
      chronic lymphocytic leukemia, and miR-17-92 regulates the tumor suppressors p21,
      Pten and Bim in aggressive B-cell lymphomas. Dysregulation of other miRNA,
      including miR-21, miR-29, miR-150 and miR-155, have also been shown to play
      crucial roles in the pathogenesis of aggressive transformed, high-grade and
      refractory lymphomas. Addition of miRNA dysregulation to the original genetic
      events likely enhances tumorigenicity of malignant lymphoma through activation of
      one or more signaling pathways. 

PMID- 23551856
TI  - Effect of pioglitazone on body composition and bone density in subjects with
      prediabetes in the ACT NOW trial.
AB  - AIMS: This study examined the effects of pioglitazone on body weight and bone
      mineral density (BMD) prospectively in patients with impaired glucose tolerance
      as pioglitazone (TZD) increases body weight and body fat in diabetic patients and
      increases the risk of bone fractures. METHODS: A total of 71 men and 163 women
      aged 49.3 (10.7) years [mean (s.d.)]; body mass index (BMI), 34.5 (5.9) kg/m(2)
      were recruited at five sites for measurements of body composition by dual energy
      X-ray absorptiometry at baseline and at conversion to diabetes or study end, if
      they had not converted. RESULTS: Mean follow-up was 33.6 months in the
      pioglitazone group and 32.1 months in the placebo group. Body weight increased
      4.63 +/- 0.60 (m +/- s.e.) kg in the pioglitazone group compared to 0.98 +/- 0.62
      kg in the PIO group (p < 0.0001). Body fat rose 4.89 +/- 0.42 kg in the
      pioglitazone group compared to 1.41 +/- 0.44 kg, (p < 0.0001) in placebo-treated
      subjects. The increase in fat was greater in legs and trunk than in the arms. BMD
      was higher in all regions in men and significantly so in most. PIO decreased BMD
      significantly in the pelvis in men and women, decreased BMD in the thoracic spine
      and ribs of women and the lumbar spine and legs of men. Bone mineral content also
      decreased significantly in arms, legs, trunk and in the total body. CONCLUSIONS:
      Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in
      several regions of the body.

PMID- 23551857
TI  - A conceptual framework for understanding chronic pain in patients with HIV.
AB  - Chronic pain is common in persons with HIV and is often associated with
      psychiatric illness and substance abuse. Current literature links psychiatric
      illness and substance abuse with worse HIV outcomes; however, the relationship of
      chronic pain, alone and in the context of psychiatric illness and substance
      abuse, to outcomes in HIV has not been described. To develop this new area of
      inquiry, we propose an adapted biopsychosocial framework specifically for chronic
      pain in HIV. This framework will describe these relationships and serve as a
      conceptual framework for future investigations.

PMID- 23551858
TI  - p.His165Pro: a novel SOX9 missense mutation of campomelic dysplasia.
AB  - Campomelic dysplasia (CD) is a rare skeletal dysplasia caused by mutation in the
      SOX9 gene located on chromosome 17q24.3-q25.1, which regulates testis and
      chondrocyte development. Severe bowing of the long bones was seen at second
      trimester scan. DNA analysis demonstrated a previously unreported de novo
      missense mutation in p.His165Pro. Ultrasound-based, molecular biology diagnosis
      led to early therapeutic termination of pregnancy. Histologic examination of the
      femoral epyphyseal growth plate confirmed scanty proliferation zone and
      maturation zone with degenerated chondrocytes.

PMID- 23551859
TI  - Distinct functions of nuclear distribution proteins LIS1, Ndel1 and NudCL in
      regulating axonal mitochondrial transport.
AB  - Neurons critically depend on the long-distance transport of mitochondria. Motor
      proteins kinesin and dynein control anterograde and retrograde mitochondrial
      transport, respectively in axons. The regulatory molecules that link them to
      mitochondria need to be better characterized. Nuclear distribution (Nud) family
      proteins LIS1, Ndel1 and NudCL are critical components of cytoplasmic dynein
      complex. Roles of these Nud proteins in neuronal mitochondrial transport are
      unknown. Here we report distinct functions of LIS1, Ndel1 and NudCL on axonal
      mitochondrial transport in cultured hippocampal neurons. We found that LIS1
      interacted with kinsein family protein KIF5b. Depletion of LIS1 enormously
      suppressed mitochondrial motility in both anterograde and retrograde directions.
      Inhibition of either Ndel1 or NudCL only partially reduced retrograde
      mitochondrial motility. However, knocking down both Ndel1 and NudCL almost
      blocked retrograde mitochondrial transport, suggesting these proteins may work
      together to regulate retrograde mitochondrial transport through linking dynein
      LIS1 complex. Taken together, our results uncover novel roles of LIS1, Ndel1 and
      NudCL in the transport of mitochondria in axons.

PMID- 23551860
TI  - Anatomy and development of the endodermis and phellem of Quercus suber L. roots.
AB  - Quercus suber L. has been investigated with special attention to the stem bark
      and its cork formation layer, but excluding the roots. Roots are the location of
      infection by pathogens such as Phytophthora cinnamomi responsible for the tree's
      sudden death. It is widely accepted that suberin establishes boundaries within
      tissues, serves as a barrier against free water and ion passage, and works as a
      shield against pathogen attacks. We followed the suberization of young secondary
      roots of cork oak. The first suberin deposition detectable by transmission
      electron microscopy (TEM) and neutral red (NR) was in the endoderm Casparian
      strips. Casparian strips are not detected by Sudan red 7B and Fluorol yellow (FY)
      that specifically stain lamellae suberin. Reaction to Sudan was verified in the
      endodermis and later on in phellem cells that resulted from the phellogen. Under
      TEM, the Sudan and FY-stained cells showed clear suberin lamellae while the newer
      formed phellem cells displayed a distinct NR signal compared to the outermost
      phellem cells. We concluded that suberin chemical components are arranged
      differently in the cell wall according to the physiological role or maturation
      stage of a given tissue.

PMID- 23551861
TI  - Complications associated with retained foreign bodies from infected penile
      implants: proposal for the use of an implant-specific checklist at the time of
      device removal.
AB  - INTRODUCTION: Infection of a penile prosthesis requires that all device hardware
      and associated foreign materials are removed, irrespective of whether a salvage
      procedure will be performed. Failure to remove all foreign bodies from the
      operative field may result in persistent infection, necessitating surgical
      intervention. AIM: To review our experience with complications arising from
      retained foreign bodies following removal of an infected penile prosthesis. We
      highlight the clinical features that should raise suspicion of retained device
      associated materials, and also the role of imaging in evaluating these patients.
      Finally, a rational approach to prevent these occurrences is proposed with the
      implementation of an implant-specific checklist. METHODS: Medical records and
      imaging studies of patients presenting to our center with retained foreign bodies
      following removal of an infected penile prosthesis were reviewed. MAIN OUTCOME
      MEASURES: Clinical and radiologic details of each of these cases were abstracted,
      including patient demographics, presenting symptoms, characteristics of retained
      materials, bacterial cultures, treatment, and follow-up. RESULTS: Presenting
      symptoms included: (i) persistent and relapsing drainage from cutaneous fistulae;
      (ii) cellulitis overlying an infected reservoir; (iii) persistent penile pain;
      and (iv) an asymptomatic individual requesting elective placement of a second
      implant. Infected foreign materials retrieved included: two rear-tip extenders, a
      tubing connector, two infected reservoirs, and nonabsorbable mesh. Preoperative
      computerized tomography scan confirmed the presence and the location of all of
      these materials. Using this data, we propose using an implant-specific checklist
      to insure removal of all device-related foreign bodies when explanting an
      infected penile prosthesis. CONCLUSIONS: A number of adverse sequelae may result
      from inadvertently leaving behind device-related materials when an infected
      implant is removed. Ultimately it is the responsibility of the surgeon removing
      an infected implant to insure that all device components and associated materials
      are removed. We believe that implementing a two-step implant-specific checklist
      is a rational prevention strategy.

PMID- 23551862
TI  - The epidemiology of arrhythmia in infants: a population-based study.
AB  - AIM: Cardiac arrhythmias are an important cause of morbidity in infants. Although
      the spectrum of types of arrhythmia has been reported, there has been no previous
      population-based study of the incidence of arrhythmias in infancy. Our aim was to
      define the population incidence of arrhythmia in infants. METHODS: We based this
      study on the Northern Region of England with a resident population of 3.1 million
      and an annual live birth rate of 33,000. We identified all clinically significant
      arrhythmias in infants in 1991-2010 from the regional cardiac database. All
      diagnoses were based on analysis of the electrocardiogram. Infants with only the
      substrate for arrhythmia (such as QT prolongation or ventricular pre-excitation)
      were excluded. RESULTS: In 20 years, there were 662,698 live births. We
      identified 162 cases of newly diagnosed arrhythmia of which 22 had associated
      structural cardiovascular malformations. The incidence of arrhythmia was 24.4 per
      100,000 live births. The most common arrhythmia was atrioventricular re-entry
      tachycardia with an incidence of 16.3 per 100,000. Complete atrioventricular
      block and atrial flutter both occurred at 2.1 cases per 100,000 live births, and
      other arrhythmias were rare. CONCLUSIONS: This study is the first to report a
      population incidence of arrhythmia in infants.

PMID- 23551863
TI  - Efficacy of Mitomycin C for postoperative endoscopic sinus surgery: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Mitomycin C has recently been used to prevent nasal synechiae and
      sinus ostium stenosis after endoscopic sinus surgery. OBJECTIVE OF REVIEW: To
      compare nasal synechiae rate between topical Mitomycin C and saline or no
      treatment. TYPE OF REVIEW: Systematic review and meta-analysis. DATA SOURCES:
      MEDLINE, SCOPUS, and Cochrane Register of Controlled Trials databases were used
      to identify studies up to January 2013. EVALUATION METHOD: Data were
      independently extracted by two reviewers (PN and KT). Studies which compared
      topical Mitomycin C with control where the outcomes of interest were nasal
      synechiae or sinus ostium stenosis were included. Baseline study characteristics,
      quality of study, numbers of patients between treatment and control groups,
      outcomes, and adverse events were extracted. A multivariate meta-analysis was
      separately applied for each outcome (nasal synechiae and maxillary sinus ostium
      stenosis). RESULTS: Among 11 included studies, most studies used Mitomycin C dose
      of 0.4-0.5 mg/mL 1-5 mL in the middle meatus for 5 min duration. Eight studies
      reported synechiae with 281 and 281 nasal cavities received Mitomycin C and
      saline, respectively. For outcome of nasal synechiae, a multivariate meta
      analysis suggested that Mitomycin C was associated with a 66% (RR = 0.34, 95% CI:
      0.18-0.65) lower risk of nasal synechiae with moderate heterogeneity (I(2) = 43%,
      95% CI: 0-77%). Subgroup analyses by age and history of revision could reduce the
      degree of heterogeneity. Mitomycin C benefits were found in subgroups of age <=
      40 years (RR = 0.27, 95% CI: 0.05-1.50) and patients without any history of
      revision (RR = 0.19, 95% CI: 0.06-0.58). Five studies with 134 and 140 nasal
      cavities for Mitomycin C and saline were included in pooling of maxillary sinus
      ostium stenosis. Mitomycin C was associated with 74% (RR = 0.26, 95% CI: 0.12
      0.54) lower risk of maxillary sinus ostium stenosis when compared with saline
      with low heterogeneity (I(2) = 5%, 95% CI: 0-85%). There was no evidence of
      publication bias for both poolings. CONCLUSION: Applying Mitomycin C topically
      after endoscopic sinus surgery could reduce the risk of nasal synechiae and
      maxillary sinus ostium stenosis in short term by 66% and 74%, respectively. The
      treatment effects may be more beneficial in patients aged 40 years or younger or
      in patients without history of revision. However, our results were based on
      pooling trials with questionable methodological quality. Further trials with good
      research methodology and long-term follow-up should be conducted to confirm our
      results.

PMID- 23551864
TI  - 'Step-port' laparoscopic cystgastrostomy for the management of organized solid
      predominant post-acute fluid collections after severe acute pancreatitis.
AB  - BACKGROUND: Post-acute pancreatic collections (PAPCs) may require intervention
      when persistent, large or symptomatic. An open cystgastrostomy is an effective
      treatment option particularly for larger, solid predominant collections. A
      laparoscopic cystgastrostomy (LCG) as initially described, could be technically
      challenging. This report describes the evolution of the operative technique and
      the results from LCG in a tertiary referral centre. METHODS: Retrospective
      analysis of the unit's prospectively populated database was conducted. All
      patients who underwent a surgical cystgastrostomy (SCG) were identified. Patient
      demographics, outcome and complications were collected and analysed. RESULTS:
      Forty-four patients underwent SCG: 8 open and 36 laparoscopic. Of the 36 LCG, 6
      required open conversion, although with evolution of the technique all of the
      last 17 cases were completed laparoscopically. The median interquartile range
      (IQR) length of stay in patients completed laparoscopically was 6 (2-10) compared
      with 15.5 days (8-19) in those patients who were converted (P = 0.0351). The only
      peri-operative complication after a LCG was a self-limiting upper
      gastrointestinal bleed. With a median (IQR) follow-up of 891 days (527-1495) one
      patient required re-intervention for a residual collection with no recurrent
      collections identified. CONCLUSION: LCG is a safe and effective procedure in
      patients with large, solid predominant PAPCs. With increased experience and
      technical expertise conversion rates can be lowered and outcome optimized.

PMID- 23551865
TI  - Epidemiology and sites of involvement of invasive fungal infections in patients
      with haematological malignancies: a 20-year autopsy study.
AB  - Autopsy studies remain an essential tool for understanding the patterns of fungal
      disease not detected ante mortem with current diagnostic approaches. We collected
      data concerning the microbiological trends, patient clinical characteristics and
      sites of involvement for invasive fungal infections (IFIs) identified at autopsy
      in a single large cancer treatment centre over a 20-year period (1989-2008). The
      autopsy rate and IFI prevalence both declined significantly during the study
      period. The prevalence of Aspergillus spp. decreased significantly from the first
      15 years of the study (from 0.12 to 0.14 cases per 100 autopsies to 0.07 in 2004
      2008; P = 0.04), with only Mucorales accounting for a greater proportion of IFIs
      over the duration of the study period (0.06 to 0.2 cases per 100 autopsies, P =
      0.04). After 2003, moulds accounted for the majority of infections identified at
      autopsy in the spleen, kidney, heart and gastrointestinal tract. Despite a trend
      of decreasing prevalence from 1989 to 2004, invasive candidiasis increased in
      prevalence during later periods 2004-2008 (0.02-0.05 per 100 autopsies) with
      decreasing kidney, heart and spleen involvement. Despite a declining autopsy
      rate, these data suggest a decreasing prevalence overall of IFIs with changing
      patterns of dissemination in patients with haematological malignancies.

PMID- 23551866
TI  - Effects of spermatozoa-oviductal cell coincubation time and oviductal cell age on
      spermatozoa-oviduct interactions.
AB  - The oviduct plays a crucial role in sperm storage, maintenance of sperm viability
      and sperm transport to the site of fertilisation. The aim of the present study
      was to investigate the effects of oviductal cell culture passage number,
      oviductal cell age and spermatozoa-oviduct coincubation times on gene expression
      in oviductal cells. Immortalised oviductal epithelial cells (OPEC) obtained from
      two different cell passages (36 and 57) were subcultured three times with and
      without spermatozoa for 24 h (control group). In a second study, OPEC were
      cocultured with spermatozoa for different time intervals (0, 4, 12 and 24 h).
      Expression of adrenomedullin (ADM), heat shock 70 kDa protein 8 (HSPA8) and
      prostaglandin E synthase (PGES) in OPEC was measured by quantitative polymerase
      chain reaction. The expression of ADM and HSPA8 was decreased significantly in
      OPEC cells from Passage 57, particularly in the later subculture group. These
      effects on HSPA8, but not ADM, expression in OPEC were further altered after
      coculture with spermatozoa for 24 h. We also demonstrated that spermatozoa
      oviduct coculture for 12 and 24 h resulted in significantly higher expression of
      ADM, HSPA8 and PGES in OPEC. Overall, the data suggest that the OPEC lose some of
      their properties as a result of oviductal cell aging and that there are
      spermatozoa-oviduct interactions leading to increased oviductal cell gene
      expression.

PMID- 23551867
TI  - Screening pigs for xenotransplantation: prevalence and expression of porcine
      endogenous retroviruses in Gottingen minipigs.
AB  - BACKGROUND: To establish the safety of xenotransplantation when cells, tissues,
      or organs of pigs are used, an effective screening for potential zoonotic
      microorganisms has to be performed. In doing so, special attendance has to be
      paid to porcine endogenous retroviruses (PERVs) that are widely distributed as
      proviruses in the genome of pigs. PERV-A and PERV-B are present in all pigs, they
      infect human cells in vitro and therefore represent a direct risk. PERV-C infects
      only pig cells; however, recombinant PERV-A/C infecting human cells and
      replicating at a higher rate were found in pigs indicating an indirect risk. To
      prevent the transmission of PERV, it was suggested to use animals characterized
      by a low expression of PERV-A and PERV-B that are free of PERV-C and cannot
      generate recombinants. Gottingen minipigs are used for numerous biomedical
      investigations and they are well characterized; however, the prevalence and the
      expression of PERV in these animals were not yet investigated. METHODS: The
      presence and expression of all PERVs including a new variant (nv) of PERV-C and
      PERV-A/C were analyzed using PCR and real-time PCR methods. Altogether, 15
      animals belonging to different families were analyzed. To make a low expression
      better measurable, peripheral blood mononuclear cells (PBMCs) of the animals were
      stimulated with phytohaemagglutinin generally increasing the expression of PERV
      and allowing a better classification into animals with high and low expression.
      As a major end point, the release of virus particles able to infect susceptible
      human 293 cells was investigated. RESULTS: PERV-A, PERV-B, PERV-C, and PERV-Cnv
      were found in the genome of all investigated Gottingen minipigs, but recombinant
      PERV-A/Cs were not found. When the expression of PERV was compared with that in
      previously analyzed pig strains, it was higher than in German landrace and some
      other pigs, but lower than in Yucatan miniature pigs. Virus particles able to
      infected human 293 cells were not detected even after mitogen treatment of the
      PBMCs. CONCLUSION: The Gottingen minipigs are well defined concerning their
      physiologic parameters, their health status, and their genetics, and therefore,
      they may be considered as donor animals for at least cell xenotransplantation.
      When the prevalence and the expression of PERVs were analyzed in these animals,
      it was demonstrated that although PERV-A, -B, and -C proviruses were found in all
      animals, their expression was low. Additional investigations are required to
      assess the suitability of Gottingen minipigs and other animals for
      xenotransplantation in terms of microbiological safety.

PMID- 23551868
TI  - Improving risk stratification in patients with prostate cancer managed by active
      surveillance: a nomogram predicting the risk of biopsy progression.
AB  - OBJECTIVE: To develop a clinical tool that integrates different risk factors and
      provides individual predictions of the risk of biopsy progression in patients
      with prostate cancer managed by active surveillance. MATERIALS AND METHODS: Our
      analysis included 205 patients on active surveillance, each of whom had had at
      least two surveillance biopsies. We used the Cox proportional hazard regression
      model to analyse the association between different risk factors and progression
      free survival over successive biopsies. This multivariate model was then used to
      develop a nomogram. Discrimination and calibration of the nomogram were
      internally validated using 200 bootstrap resamplings. RESULTS: The median follow
      up of patients free of progression was 4.6 years. A total of 58 (28%) patients
      experienced progression. Factors significantly associated with progression were:
      overall number of positive cores in the diagnostic and first surveillance
      biopsies, race and prostate-specific antigen density. The bootstrapping
      concordance index of the nomogram including these variables was 81%. The nomogram
      tended to underestimate the probability of progression but it identified fairly
      accurately the distinct groups of patients at low, intermediate and high risk of
      progression. CONCLUSIONS: In the development cohort, the nomogram was able to
      separate patients with respect to their risk of biopsy progression. Since
      accurate risk stratification is essential to optimize patient care, this tool, if
      external validation confirms its performance, may prove useful for both the
      counselling and management of patients with low-volume, Gleason 6 prostate
      cancer.

PMID- 23551869
TI  - Assessment of human exposures to animal vaccines using poison control records,
      2000-2009.
AB  - To characterize human exposures to vaccines intended for animals, evaluate the
      human risk due to these exposures and determine whether there is sufficient
      surveillance in place to monitor them. Retrospective analysis of surveillance
      data (2000-2009). Information collected by poison specialists during calls
      reporting human exposure to an animal vaccine product, made to one of the 57
      United States Poison Control Centers. Data from the National Poison Data System
      were analysed to determine the number of calls due to human exposures to animal
      vaccines, and descriptive statistics were generated to characterize the exposures
      by age, gender, medical outcome, exposure site, exposure route, vaccine type and
      intended species, aetiologic agent, call date and exposure reason. Overall, the
      human health effects were minor, primarily due to unintentional parenteral
      exposure. Less than 15% of the reports were classified as occupational, and 80%
      of the exposures took place outside of a workplace or healthcare facility. Almost
      60% of calls were due to exposure to the West Nile Virus vaccine; the others
      distributed among a variety of vaccines. Unintentional exposure to animal
      vaccines appears to occur almost exclusively among untrained individuals who may
      benefit from more effective education about the risks and benefits of
      administering vaccines. Improved reporting of adverse outcomes is essential to
      adequately define the extent of human exposure and risks associated with
      availability of new vaccines. 

PMID- 23551871
TI  - Intravenous versus intramuscular epinephrine administration during
      cardiopulmonary resuscitation - a pilot study in piglets.
AB  - BACKGROUND: Early epinephrine administration in cardiac arrest seems to be
      advantageous to achieve return of spontaneous circulation (ROSC). Because
      intravenous (i.v.) or intraosseous access is not always immediately available,
      this study compares efficacy of early intramuscular (i.m.) epinephrine
      administration with early and delayed i.v. epinephrine injection in an animal
      cardiac arrest model. METHODS: Piglets anesthetized with sevoflurane were
      intoxicated by an i.v. ropivacaine infusion until circulatory arrest. After 1 min
      basic life support (chest compression and ventilation), epinephrine i.v. (10
      MUg.kg(-1), group IV) or epinephrine i.m. (100 MUg.kg(-1), group IM) or normal
      saline (group NS) was applied. Further doses of epinephrine were given in group
      IV every 4 min and in group IM after 10 min if required. Twenty-one minutes after
      circulatory arrest, i.v. epinephrine - as necessary - was given to all animals.
      Thus, group NS represents late epinephrine administration. Outcomes were survival
      and time to ROSC. RESULTS: Twenty-four pigs aged 19.5 (median, interquartile
      range 16-22) days, weighing 5.4 (5.0-5.7) kg were investigated. Total amount of
      ropivacaine administered was 8.9 (8.1-10.1) mg.kg(-1). Cardiac rhythm before
      starting CPR was pulseless electric activity and asystole in 15 and 9 pigs,
      respectively. Eight, seven, and four pigs survived in group IV, IM, and NS.
      Focusing on surviving animals, time to ROSC was 2, 4 and 19.5 min in group IV,
      IM, and NS. CONCLUSIONS: Early i.m. epinephrine provided similar survival
      compared with early i.v. epinephrine and was superior to delayed epinephrine
      administration in resuscitation of ropivacaine-induced cardiac arrest in piglets.

PMID- 23551872
TI  - Biological aspects as a rule for single implant placement. The 3A-2B rule: a
      clinical report.
AB  - For an implant restoration to be both esthetically and functionally successful,
      the prosthodontist must conduct a thorough treatment plan and complete a
      prosthesis design. The prosthodontist must carefully calculate the space needed
      for the restoration and soft tissue in the restoration process. The restoration
      and soft tissue are affected by the three-dimensional (3D) position of the
      implant, as the implant's depth determines the ideal length of the crown. When
      determining the 3D position of the implant, the clinician must consider the
      biological aspects required to ensure the restoration's biological integration
      with the patient's hard and soft tissues. The restoration must be the first
      component considered in the treatment plan. In addition, the clinician must
      understand that the distance between the cervical contour (of the planned
      restoration) and the level of the bone will dictate how the surgical and
      prosthetic treatment plan is enacted. In this report, a novel Radiographic
      Biological Ruler(c) (with biological information) was used to help facilitate the
      treatment plan's analysis. 

PMID- 23551873
TI  - Novel mouse model for Gardner syndrome generated by a large-scale N-ethyl-N
      nitrosourea mutagenesis program.
AB  - Mutant mouse models are indispensable tools for clarifying the functions of genes
      and elucidating the underlying pathogenic mechanisms of human diseases. We
      carried out large-scale mutagenesis using the chemical mutagen N-ethyl-N
      nitrosourea. One specific aim of our mutagenesis project was to generate novel
      cancer models. We screened 7012 animals for dominant traits using a necropsy test
      and thereby established 17 mutant lines predisposed to cancer. Here, we report on
      a novel cancer model line that developed osteoma, trichogenic tumor, and breast
      cancer. Using fine mapping and genomic sequencing, we identified a point mutation
      in the adenomatous polyposis coli (Apc) gene. The Apc1576 mutants bear a nonsense
      mutation at codon 1576 in the Apc gene. Although most Apc mutant mice established
      thus far have multifocal intestinal tumors, mice that are heterozygous for the
      Apc1576 mutation do not develop intestinal tumors; instead, they develop
      multifocal breast cancers and trichogenic tumors. Notably, the osteomas that
      develop in the Apc1576 mutant mice recapitulate the lesion observed in Gardner
      syndrome, a clinical variant of familial adenomatous polyposis. Our Apc1576
      mutant mice will be valuable not only for understanding the function of the Apc
      gene in detail but also as models of human Gardner syndrome. 

PMID- 23551874
TI  - INDACO project: a pilot study on incidence of comorbidities in COPD patients
      referred to pneumology units.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is often associated with
      comorbidities, especially cardiovascular, that have a heavy burden in terms of
      hospitalization and mortality. Since no conclusive data exist on the prevalence
      and type of comorbidities in COPD patients in Italy, we planned the INDACO
      observational pilot study to evaluate the impact of comorbidities in patients
      referred to the outpatient wards of four major hospitals in Rome. METHODS: For
      each patient we recorded anthropometric and anamnestic data, smoking habits,
      respiratory function, GOLD (Global initiative for chronic Obstructive Lung
      Disease) severity stage, Body Mass Index (BMI), number of acute COPD
      exacerbations in previous years, presence and type of comorbidities, and the
      Charlson Comorbidity Index (CCI). RESULTS: Here we report and discuss the results
      of the first 169 patients (124 males, mean age 74+/-8 years). The prevalence of
      patients with comorbidities was 94.1% (25.2% of cases presented only one
      comorbidity, 28.3% two, 46.5% three or more). There was a high prevalence of
      arterial hypertension (52.1%), metabolic syndrome (20.7%), cancers (13.6%) and
      diabetes (11.2%) in the whole study group, and of anxiety-depression syndrome in
      females (13%). Exacerbation frequency was positively correlated with dyspnea
      score and negatively with BMI. Use of combination of bronchodilators and inhaled
      corticosteroids was more frequent in younger patients with more severe airways
      obstruction and lower CCI. CONCLUSIONS: These preliminary results show a high
      prevalence of comorbidities in COPD patients attending four great hospitals in
      Rome, but they need to be confirmed by further investigations in a larger
      patients cohort.

PMID- 23551875
TI  - Characterization of large deletions in the F8 gene using multiple competitive
      amplification and the genome walking technique.
AB  - BACKGROUND: Large deletions in the F8 gene are responsible for approximately 3%
      of severe hemophilia A (HA) cases. However, only a few breakpoints in large
      deletions have been characterized. OBJECTIVES: To identify large deletions in the
      F8 gene and to characterize the molecular mechanisms leading to these deletions.
      PATIENTS AND METHODS: We used AccuCopy technology, a copy number variation (CNV)
      genotyping method based on multiplex competitive amplification, to confirm
      deletions in index patients and to screen potential female carriers in 10 HA
      families. Also, breakpoints of these large deletions were characterized by a
      primer walking strategy and genome walking technique. RESULTS: Ten large
      deletions and four female carriers were identified by AccuCopy. The extents of
      deleted regions ranged from 1.3 to 68.5 kb. Exact breakpoints of these deletions
      were successfully characterized. Eight of them presented microhomologies at
      breakpoint junctions and several recombination-associated elements (repetitive
      elements, non-B conformation forming motifs and sequence motifs) were also
      observed in close proximity to the junctions. CONCLUSIONS: AccuCopy technology is
      a reliable and efficient tool for detecting large deletions in the F8 gene and
      identifying HA female carriers. The genome walking technique is a highly
      specific, efficient and versatile method for characterizing the deletion
      breakpoints. Molecular characterization of deletion breakpoints revealed that non
      homologous end joining and microhomology-mediated replication-dependent
      recombination were the major causative mechanisms of the 10 large deletions in
      the F8 gene.

PMID- 23551876
TI  - Role of salpingoscopy in assessing the inner fallopian tubes of infertility
      patients with ovarian endometriomas.
AB  - AIM: The aim of this study was to observe the insides of the fallopian tubes of
      patients with unilateral or bilateral endometriomas by using salpingoscopy and
      evaluate the inner cavity of the fallopian tubes according to our original
      scoring system. MATERIAL AND METHODS: From April 2008 through December 2010,
      patients with unilateral or bilateral endometriomas were recruited (n = 157,
      endometrioma group). All patients underwent laparoscopic ovarian cystectomy and
      salpingoscopy. Using salpingoscopy, we observed the tubal lumen and calculated a
      fallopian tube score (F score) paying attention to the following six results:
      adhesions, loss of mucosal folds, rounded edges of mucosal folds, debris, foreign
      bodies, and abnormal vessels. The F scores were compared with those of the
      unexplained infertility patients who received those same procedures during the
      same period (n = 235; control group). RESULTS: Slightly more than three-quarters
      (75.9%) of the patients in the endometrioma group received F scores of 0, and
      this percentage was significantly higher than that for the control group (139/235
      = 59.1%, P < 0.05). The pregnancy rate after conventional treatment for the
      endometrioma group was 21.7%, and all pregnant patients had achieved an F score
      of less than 2. CONCLUSION: It is highly possible that infertility patients with
      ovarian endometriomas are more likely to have intact fallopian tubes, by
      comparison with infertility patients who do not have ovarian endometriomas.

PMID- 23551877
TI  - Mast cell tumors in Mongolian gerbils infected with Helicobacter pylori that had
      been pretreated with 30% NaCl.

PMID- 23551878
TI  - Genomic imbalances in patients with a clinical presentation in the spectrum of
      Cornelia de Lange syndrome.
AB  - BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant
      disorder characterised by facial dysmorphism, growth and psychomotor
      developmental delay and skeletal defects. To date, causative mutations in the
      NIPBL (cohesin regulator) and SMC1A (cohesin structural subunit) genes account
      for > 50% and 6% of cases, respectively. METHODS: We recruited 50 patients with a
      CdLS clinical diagnosis or with features that overlap with CdLS, who were
      negative for mutations at NIPBL and SMC1A at molecular screening. Chromosomal
      rearrangements accounting for the clinical diagnosis were screened for using
      array Comparative Genomic Hybridisation (aCGH). RESULTS: Four patients were shown
      to carry imbalances considered to be candidates for having pathogenic roles in
      their clinical phenotypes: patient 1 had a 4.2 Mb de novo deletion at chromosome
      20q11.2-q12; patient 2 had a 4.8 Mb deletion at chromosome 1p36.23-36.22; patient
      3 carried an unbalanced translocation, t(7;17), with a 14 Mb duplication of
      chromosome 17q24.2-25.3 and a 769 Kb deletion at chromosome 7p22.3; patient 4 had
      an 880 Kb duplication of chromosome 19p13.3, for which his mother, who had a mild
      phenotype, was also shown to be a mosaic. CONCLUSIONS: Notwithstanding the
      variability in size and gene content of the rearrangements comprising the four
      different imbalances, they all map to regions containing genes encoding factors
      involved in cell cycle progression or genome stability. These functional
      similarities, also exhibited by the known CdLS genes, may explain the phenotypic
      overlap between the patients included in this study and CdLS. Our findings point
      to the complexity of the clinical diagnosis of CdLS and confirm the existence of
      phenocopies, caused by imbalances affecting multiple genomic regions, comprising
      8% of patients included in this study, who did not have mutations at NIPBL and
      SMC1A. Our results suggests that analysis by aCGH should be recommended for CdLS
      spectrum cases with an unexplained clinical phenotype and included in the flow
      chart for diagnosis of cases with a clinical evaluation in the CdLS spectrum.

PMID- 23551879
TI  - Using structural neuroanatomy to identify trauma survivors with and without post
      traumatic stress disorder at the individual level.
AB  - BACKGROUND: At present there are no objective, biological markers that can be
      used to reliably identify individuals with post-traumatic stress disorder (PTSD).
      This study assessed the diagnostic potential of structural magnetic resonance
      imaging (sMRI) for identifying trauma-exposed individuals with and without PTSD.
      METHOD: sMRI scans were acquired from 50 survivors of the Sichuan earthquake of
      2008 who had developed PTSD, 50 survivors who had not developed PTSD and 40
      healthy controls who had not been exposed to the earthquake. Support vector
      machine (SVM), a multivariate pattern recognition technique, was used to develop
      an algorithm that distinguished between the three groups at an individual level.
      The accuracy of the algorithm and its statistical significance were estimated
      using leave-one-out cross-validation and permutation testing. RESULTS: When
      survivors with PTSD were compared against healthy controls, both grey and white
      matter allowed discrimination with an accuracy of 91% (p < 0.001). When survivors
      without PTSD were compared against healthy controls, the two groups could be
      discriminated with accuracies of 76% (p < 0.001) and 85% (p < 0.001) based on
      grey and white matter, respectively. Finally, when survivors with and without
      PTSD were compared directly, grey matter allowed discrimination with an accuracy
      of 67% (p < 0.001); in contrast the two groups could not be distinguished based
      on white matter. CONCLUSIONS: These results reveal patterns of neuroanatomical
      alterations that could be used to inform the identification of trauma survivors
      with and without PTSD at the individual level, and provide preliminary support to
      the development of SVM as a clinically useful diagnostic aid.

PMID- 23551880
TI  - Stroke in primary hyperoxaluria type I.
AB  - We report the case of a 27-year-old man with a history of previously undiagnosed
      renal disease that presented with multiple cerebrovascular infarctions. Workup
      for traditional causes of cerebrovascular infarction including cardiac telemetry,
      multiple echocardiograms, and hypercoagulative workup was negative. However, a
      transcranial Doppler detected circulating microemboli at the rate of 14 per hour.
      A serum oxalate level greater than the supersaturation point of calcium oxalate
      was detected, providing a potential source of the microemboli. Furthermore,
      serial imaging recorded rapid mineralization of the infarcted territories. In the
      absence of any proximal vessel irregularities, atherosclerosis, valvular
      abnormalities, arrhythmias, or systemic shunt as potential stroke etiology in
      this patient, we propose that circulating oxalate precipitate may be a potential
      mechanism for stroke in patients with primary oxalosis. 

PMID- 23551881
TI  - Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood
      onset diabetes.
AB  - Monogenic diabetes due to mutations in the transcription factor genes hepatocyte
      nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody
      negative, familial diabetes with residual insulin secretion. We report two
      sisters with childhood onset diabetes who are both heterozygous for the most
      common mutation in each of two transcription factors, HNF1A, and HNF4A. The
      proband was diagnosed with diabetes at 7 yr of age and treated with insulin for 4
      yr. Her genetic diagnosis resulted in transition to sulfonylureas for one and a
      half years before insulin therapy was re-initiated due to declining glycemic
      control. Her sister was diagnosed with diabetes at 14 yr of age, treated
      initially with insulin but has been well controlled on oral sulfonylurea therapy
      for over 2 yr. Both sisters inherited the HNF4A gene mutation R127W from their
      mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. The
      father was diagnosed with diabetes at 45 yr of age. Their brother is heterozygous
      for the HNF4A R127W mutation. Both the brother and mother have normal glucose
      tolerance at the ages of 16 and 46 yr, respectively. Digenic inheritance of HNF1A
      and HNF4A mutations is very rare and has only been reported in two families where
      conclusive evidence for the pathogenicity of their mutations was lacking. Follow
      up studies in this family co-segregating the two most commonly reported
      HNF1A/HNF4A mutations will be informative for understanding the effect of digenic
      inheritance upon phenotypic severity and response to sulfonylurea therapy. 

PMID- 23551882
TI  - Prior infection of pigs with a recent human H3N2 influenza virus confers minimal
      cross-protection against a European swine H3N2 virus.
AB  - BACKGROUND: H3N2 influenza viruses circulating in humans and European pigs
      originate from the pandemic A/Hong Kong/68 virus. Because of slower antigenic
      drift in swine, the antigenic divergence between swine and human viruses has been
      increasing. It remains unknown to what extent this results in a reduced cross
      protection between recent human and swine H3N2 influenza viruses. OBJECTIVES: We
      examined whether prior infection of pigs with an old [A/Victoria/3/75 (A/Vic/75)]
      or a more recent [A/Wisconsin/67/05 (A/Wis/05)] human H3N2 virus protected
      against a European swine H3N2 virus [sw/Gent/172/08 (sw/Gent/08)]. Genetic and
      antigenic relationships between sw/Gent/08 and a selection of human H3N2 viruses
      were also assessed. RESULTS: After challenge with sw/Gent/08, all challenge
      controls had high virus titers in the entire respiratory tract at 3 days post
      challenge and nasal virus excretion for 5-6 days. Prior infection with sw/Gent/08
      or A/Vic/75 offered complete virological protection against challenge. Pigs
      previously inoculated with A/Wis/05 showed similar virus titers in the
      respiratory tract as challenge controls, but the mean duration of nasal shedding
      was 1.3 days shorter. Unlike sw/Gent/08- and A/Vic/75-inoculated pigs, A/Wis/05
      inoculated pigs lacked cross-reactive neutralizing antibodies against sw/Gent/08
      before challenge, but they showed a more rapid antibody response to sw/Gent/08
      than challenge controls after challenge. Cross-protection and serological
      responses correlated with genetic and antigenic differences. CONCLUSIONS:
      Infection immunity to a recent human H3N2 virus confers minimal cross-protection
      against a European swine H3N2 virus. We discuss our findings with regard to the
      recent zoonotic infections of humans in the United States with a swine-origin
      H3N2 variant virus.

PMID- 23551870
TI  - Limited cross-border infections in patients newly diagnosed with HIV in Europe.
AB  - BACKGROUND: International travel plays a role in the spread of HIV-1 across
      Europe. It is, however, not known whether international travel is more important
      for spread of the epidemic as compared to endogenous infections within single
      countries. In this study, phylogenetic associations among HIV of newly diagnosed
      patients were determined across Europe. RESULTS: Data came from the SPREAD
      programme which collects samples of newly diagnosed patients that are
      representative for national HIV epidemics. 4260 pol sequences from 25 European
      countries and Israel collected in 2002-2007 were included.We identified 457
      clusters including 1330 persons (31.2% of all patients). The cluster size ranged
      between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that
      consisted only of patients originating from the same country. In addition, 135
      patients (10.2%) were in a cluster including only individuals from neighboring
      countries. Finally, 208 patients (15.6%) clustered with individuals from
      countries without a common border. Clustering with patients from the same country
      was less prevalent in patients being infected with B subtype (P-value <0.0001),
      in men who have sex with men (P-value <0.0001), and in recently infected patients
      (P-value =0.045). CONCLUSIONS: Our findings indicate that the transmission of HIV
      1 in Europe is predominantly occurring between patients from the same country.
      This could have implications for HIV-1 transmission prevention programmes.
      Because infections through travelling between countries is not frequently
      observed it is important to have good surveillance of the national HIV-1
      epidemics.

PMID- 23551883
TI  - The effects of lead and copper on the cellular architecture and metabolism of the
      red alga Gracilaria domingensis.
AB  - The effect of lead and copper on apical segments of Gracilaria domingensis was
      examined. Over a period of 7 days, the segments were cultivated with
      concentrations of 5 and 10 ppm under laboratory conditions. The samples were
      processed for light, confocal, and electron microscopy, as well as
      histochemistry, to evaluate growth rates, mitochondrial activity, protein levels,
      chlorophyll a, phycobiliproteins, and carotenoids. After 7 days of exposure to
      lead and copper, growth rates were slower than control, and biomass loss was
      observed on copper-treated plants. Ultrastructural damage was primarily observed
      in the internal organization of chloroplasts and cell wall thickness. X-ray
      microanalysis detected lead in the cell wall, while copper was detected in both
      the cytoplasm and cell wall. Moreover, lead and copper exposure led to
      photodamage of photosynthetic pigments and, consequently, changes in
      photosynthesis. However, protein content and glutathione reductase activity
      decreased only in the copper treatments. In both treatments, decreased
      mitochondrial NADH dehydrogenase activity was observed. Taken together, the
      present study demonstrates that (1) heavy metals such as lead and copper
      negatively affect various morphological, physiological, and biochemical processes
      in G. domingensis and (2) copper is more toxic than lead in G. domingensis.

PMID- 23551884
TI  - Paediatric expert witness.
AB  - Paediatricians may be asked to provide expert opinion in paediatric cases that
      come under legal consideration. This article provides suggestions to assist
      paediatricians in this role and emphasises their duty to the court when giving
      expert opinion. 

PMID- 23551885
TI  - Type 2 diabetes sits in a chair.
AB  - The incidence of type 2 diabetes (T2D) continues to skyrocket across the
      industrialized world leading to soaring medical costs, reduced quality of life
      and increased mortality rates. Therefore, a more firm understanding of the
      development of the disease and effective, low cost therapies for prevention and
      treatment are desperately needed. Accumulating evidence suggests that increased
      sedentary time (i.e. 'sitting time') combined with reduced physical activity
      levels, plays both a major role in the development of T2D and may contribute to
      the worsening of the condition after diagnosis. In this review, we cover these
      topics and use current scientific evidence to support our belief that 'type 2
      diabetes sits in a chair'. We also discuss a relatively new question that has yet
      to be examined: Would reducing sitting time be an effective treatment for T2D? 

PMID- 23551886
TI  - Testosterone replacement therapy with long-acting testosterone undecanoate
      improves sexual function and quality-of-life parameters vs. placebo in a
      population of men with type 2 diabetes.
AB  - INTRODUCTION: Sexual dysfunction, particularly erectile dysfunction (ED), is
      common in men with type 2 diabetes, occurring in up to 75% of cases. The
      prevalence of hypogonadism is also high in men with diabetes and low testosterone
      is associated with both sexual dysfunction and a reduced response to oral therapy
      for ED. AIM: This study aimed to determine the effect of testosterone replacement
      with long-acting Testosterone Undecanoate (TU) on sexual function, mood and
      quality of life vs. placebo over a treatment period of 30 weeks followed by 52
      weeks of open-label medication. The study was conducted in a primary care
      population of men with type 2 diabetes attending their primary care physician for
      routine visits. METHODS: The male diabetic populations of seven general practices
      were screened at routine diabetes visits to detect symptomatic men with total
      testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L
      or less. Two hundred eleven men were screened. A double-blind placebo-controlled
      study was conducted in 199 men with type 2 diabetes and hypogonadism treated for
      30 weeks with either 1,000 mg of TU or matching placebo followed by 52-week open
      label follow on. MAIN OUTCOME MEASURES: The primary outcome measure,
      International Index of Erectile Function (IIEF), was used to evaluate sexual
      dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression
      Scale, and Global Efficacy Question were used as secondary outcome measures to
      assess mood and self-reported quality of life. RESULTS: Testosterone replacement
      therapy with long-acting TU improved all domains of sexual function at 30 weeks
      (erectile function [EF], P = 0.005; intercourse satisfaction, P = 0.015; sexual
      desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with
      benefit as early as 6 weeks. Improvements in AMS score were significant in men
      without depression (P = 0.02) and the presence of depression at baseline was
      associated with marked reduction in response to both sexual function and
      psychological scores. All responses in sexual function continued to improve
      significantly up to 18 months with an improvement in EF score of 4.31 from
      baseline. In a small cohort of 35 men taking phosphodiesterase type 5 inhibitors,
      there was no change during the double-blind phase but a nine-point improvement in
      EF domain during 52-week open-label treatment. After 30 weeks, 46% vs. 17% of
      patients on active therapy vs. placebo felt that the treatment had improved their
      health, reaching 70% after open-label therapy. Less obese and older patients
      responded better to testosterone therapy. There were no significant adverse
      events. CONCLUSION: TU significantly improved all domains of the IIEF and patient
      reported quality of life at 30 weeks and more significantly after 52-week open
      label extension. Improvement was most marked in less obese patient and those
      without coexisting depression. In men with type 2 diabetes, trials of therapy may
      need to be given for much longer than 3-6 months suggested in current guidelines.

PMID- 23551887
TI  - What should men living with severe haemophilia need to know? The perspectives of
      Canadian haemophilia health care providers.
AB  - Haemophilia is a complex disease to manage. Home-based management of haemophilia
      has placed greater responsibility for disease management on individuals with
      haemophilia, heightening the individual's need for knowledge, particularly among
      individuals with severe haemophilia. The aim of this study was to identify and
      understand the knowledge needs and gaps of Canadian men with severe haemophilia
      from the perspectives of health care providers. A qualitative approach was
      undertaken. Data were collected using semi-structured focus groups and interviews
      with health care providers from Haemophilia Treatment Centres (HTCs) across
      Canada; data were analysed using thematic analysis. Three focus groups and two
      interviews were conducted; 13 individuals participated in this study. Health care
      providers identified the following areas of knowledge required by men with severe
      haemophilia: disease pathology, causes and consequences of bleeds, bleed
      prevention, recognition, treatment, how and when to access support, activity
      selection and risk reduction, benefits of exercise, genetic inheritance patterns,
      impact on career selection, travel and ageing. Knowledge gaps and challenges to
      knowledge provision were highlighted. In addition, providers emphasized the
      influences of timing, rapport and context on readiness to receive and assimilate
      information and recommended tailoring education to the individual and creating a
      developmental curriculum and knowledge assessment tool. Provision and uptake of
      disease knowledge is essential to patient self-management. To effectively
      receive, retain and assimilate information, individuals with severe haemophilia
      require the right information, from the right source, at the right time.
      Education should be tailored to the needs of the individual, provided throughout
      the lifespan.

PMID- 23551888
TI  - FOXO4 is necessary for neural differentiation of human embryonic stem cells.
AB  - Proteostasis is critical for maintaining cell function and proteome stability may
      play an important role in human embryonic stem cell (hESC) immortality. Notably,
      hESC populations exhibit a high assembly of active proteasomes, a key node of the
      proteostasis network. FOXO4, an insulin/IGF-1 responsive transcription factor,
      regulates proteasome activity in hESCs. We find that loss of FOXO4 reduces the
      potential of hESCs to differentiate into neural lineages. Therefore, FOXO4
      crosses evolutionary boundaries and links hESC function to invertebrate longevity
      modulation.

PMID- 23551889
TI  - What does S-palmitoylation do to membrane proteins?
AB  - S-palmitoylation is post-translational modification, which consists in the
      addition of a C16 acyl chain to cytosolic cysteines and which is unique amongst
      lipid modifications in that it is reversible. It can thus, like phosphorylation
      or ubiquitination, act as a switch. While palmitoylation of soluble proteins
      allows them to interact with membranes, the consequences of palmitoylation for
      transmembrane proteins are more enigmatic. We briefly review the current
      knowledge regarding the enzymes responsible for palmitate addition and removal.
      We then describe various observed consequences of membrane protein
      palmitoylation. We propose that the direct effects of palmitoylation on
      transmembrane proteins, however, might be limited to four non-mutually exclusive
      mechanistic consequences: alterations in the conformation of transmembrane
      domains, association with specific membrane domains, controlled interactions with
      other proteins and controlled interplay with other post-translational
      modifications.

PMID- 23551891
TI  - Medical students and psychiatry: an attitude change?

PMID- 23551890
TI  - Subthalamic deep brain stimulation improves smooth pursuit and saccade
      performance in patients with Parkinson's disease.
AB  - BACKGROUND: Deep brain stimulation (DBS) in the subthalamic nucleus (STN)
      significantly reduces symptoms of Parkinson's disease (PD) such as bradykinesia,
      tremor and rigidity. It also reduces the need for anti-PD medication, and thereby
      potential side-effects of L-Dopa. Although DBS in the STN is a highly effective
      therapeutic intervention in PD, its mechanism and effects on oculomotor eye
      movement control and particularly smooth pursuit eye movements have to date
      rarely been investigated. Furthermore, previous reports provide conflicting
      information. The aim was to investigate how DBS in STN affected oculomotor
      performance in persons with PD using novel analysis techniques. METHODS: Twenty
      five patients were eligible (22 males, 3 females) according to the clinical
      inclusion criteria: idiopathic PD responsive to L-Dopa and having had bilateral
      STN stimulation for at least one year to ensure stable DBS treatment. Fifteen
      patients were excluded due to the strict inclusion criteria applied to avoid
      interacting and confounding factors when determining the effects of DBS applied
      alone without PD medication. One patient declined participation. Nine PD patients
      (median age 63, range 59-69 years) were assessed after having their PD
      medications withdrawn overnight. They were examined with DBS ON and OFF, with the
      ON/OFF order individually randomized. RESULTS: DBS ON increased smooth pursuit
      velocity accuracy (p < 0.001) and smooth pursuit gain (p = 0.005), especially for
      faster smooth pursuits (p = 0.034). DBS ON generally increased saccade amplitude
      accuracy (p = 0.007) and tended to increase peak saccade velocity also (p =
      0.087), specifically both saccade velocity and amplitude accuracy for the 20 and
      40 degree saccades (p < 0.05). Smooth pursuit latency tended to be longer (p =
      0.090) approaching normal with DBS ON. Saccade latency was unaffected.
      CONCLUSIONS: STN stimulation from DBS alone significantly improved both smooth
      pursuit and saccade performance in patients with PD. The STN stimulation
      enhancement found for oculomotor performance suggests clear positive implications
      for patients' ability to perform tasks that rely on visual motor control and
      visual feedback. The new oculomotor analysis methods provide a sensitive vehicle
      to detect subtle pathological modifications from PD and the functional
      enhancements produced by STN stimulation from DBS alone.

PMID- 23551892
TI  - The public's priorities in health services.
AB  - BACKGROUND: Rationing in health services cannot be solved only by cost-effective
      analysis because social values play a central role in the difficult trade-off
      dilemma of prioritizing some service over others. OBJECTIVE: To examine the
      relative importance ascribed by the public to selected components of health
      services, in the national allocation of resources as well as in their personal
      insurance. METHODS: A telephone survey of a representative sample of the Israeli
      adult population (N = 1225). Two versions of the questionnaire were used. At the
      national level, interviewees were asked to assume they were the Minister of
      Health. At the personal level, interviewees were asked to choose items to be
      included in their personal complementary health insurance. RESULTS: Check-ups for
      early disease detection and nursing care for the frail elderly got the highest
      support for extra budget as well as to be included in personal insurance. Other
      items presented were fertility treatments, cardiac rehabilitation, mental health,
      dental health, programmes for preventive medicine and health promotion,
      subsidizing supplemental insurance for the poor, additional staff for primary
      clinics and building a new hospital. The lowest support was for alternative
      medicine and for cosmetic surgery. No subgroup in the Israeli society presented a
      different first priority. CONCLUSION: The Israeli public does not give high
      priority to 'nice to have' services but their selections are 'mature' and
      responsible. Rationing in health care requires listening to the public even if
      there are still many methodological limitations on how to reflect the public's
      opinion.

PMID- 23551893
TI  - Cotrimoxazole plasma levels, dialyzer clearance and total removal by extended
      dialysis in a patient with acute kidney injury: risk of under-dosing using
      current dosing recommendations.
AB  - BACKGROUND: Dosing of antibiotics in critically ill patients is challenging. It
      becomes even more difficult if renal or hepatic impairment ensue. Modern means of
      renal replacement therapy are capable of removing antibiotics to a higher rate
      than decades ago, leaving clinicians with a high degree of uncertainty concerning
      the dose of antibiotics in this patient population. Cotrimoxazole, a combination
      of trimethoprim (TMP) and sulfamethoxazole (SMX) is frequently used in the
      treatment of several infections including Pneumocystis jirovecii pneumonia (PCP).
      CASE PRESENTATION: Here we describe a patient with acute kidney injury in which
      we investigated the TMP and SMX levels during the course of an ICU stay.
      Cotrimoxazole was administered every six hours i.v. in a dose of TMP/SMX 15/75
      mg/kg/day. Extended dialysis was performed with a high-flux dialyzer. Blood
      samples, as well as pre- and postdialyzer samples and aliquots of the collected
      spent dialysate were collected.Observed peak concentrations (Cmax) were 7.51 mg/l
      for TMP and 80.80 mg/l for SMX. Decline of blood levels during extended dialysis
      (TMP 64%; SMX 84%) was mainly due to removal by the dialysis procedure,
      illustrated by the high dialyzer clearances (median of 4 extended dialysis
      sessions: TMP 94.0 / SMX 51.0 ml/min), as well as by the absolute amount of both
      substances in the collected spent dialysate (median of 6 extended dialysis
      sessions: TMP 556 mg / SMX 130 mg). Within the limitation of a case report our
      data from 4 consecutive extended dialysis sessions suggest that this procedure
      substantially removes both TMP and SMX. CONCLUSIONS: Dose reduction, which is
      usually advocated in patients with acute kidney injury under renal replacement
      therapy, might lead to significant under-dosing. Pharmacokinetic studies for
      TMP/SMX dosing in this patient population are necessary to allow adequate dosing.

PMID- 23551895
TI  - Comment on 'response to "comment on 'levels of soluble endothelial selectin in
      umbilical cord serum are influenced by gestational age and histological
      chorioamnionitis, but not by pre-eclampsia' " '.

PMID- 23551894
TI  - High levels of FOXP3+ regulatory T cells in gastric MALT lymphoma predict
      responsiveness to Helicobacter pylori eradication.
AB  - BACKGROUND: Although Helicobacter pylori eradication is a first-line treatment of
      gastric MALT lymphoma, roughly 25% of patients do not respond to treatment. CD4+
      FOXP3+ regulatory T (Treg) cells regulate immune responses in physiological
      conditions and various inflammatory conditions, including H. pylori-associated
      diseases. Our goal was to determine how Treg cells affect responsiveness to H.
      pylori eradication therapy. MATERIALS AND METHODS: We performed dual
      immunohistochemistry for CD4 and FOXP3 to evaluate the prevalence of FOXP3+ Treg
      cells in the stomach of 63 patients with MALT lymphoma and 55 patients with
      chronic active gastritis. Receiver operating characteristic analysis was carried
      out to determine the best cut-off point in differentiating H. pylori eradication
      responders from nonresponders. RESULTS: Both the FOXP3+/CD4+ cell ratio and the
      absolute number of FOXP3+ cells per high-power field in MALT lymphoma were
      significantly greater in H. pylori eradication responders compared with
      nonresponders, suggesting that Treg cells function in regression mechanisms of
      MALT lymphomas. Cut-off points with good sensitivities and specificities were
      obtained to predict eradication outcome. CONCLUSIONS: A high number of Treg cells
      or a high ratio of Treg cells to the total number of CD4+ T cells in gastric MALT
      lymphoma could predict responsiveness to eradication therapy.

PMID- 23551896
TI  - Contrast ultrasound for the quantification of deep vein thrombosis in living
      mice: effects of enoxaparin and P2Y12 receptor inhibition.
AB  - BACKGROUND/OBJECTIVES: We examined the applicability of contrast-enhanced
      ultrasound (CEUS) for imaging of murine deep vein thrombosis (DVT) and measured
      the effects of enoxaparin, ticagrelor and P2Y(12) receptor deficiency in vivo.
      METHODS: Deep vein thrombosis was induced by exposure to ferric chloride or
      ligation of the infrarenal vena cava of C57BL/6 mice after pretreatment with
      enoxaparin, ticagrelor or vehicle and in P2Y(12-/-) mice. Initial thrombus growth
      was visualized by intravital microscopy. Thrombi were weighed and examined by
      immunohistochemistry. CEUS was performed with a standard ultrasound system (Vivid
      7, GE Healthcare) in the open abdominal cavity after injection of stabilized
      sulphur hexafluoride microbubbles. RESULTS: Incubation with ferric chloride
      resulted in non-occluding platelet-containing thrombus growth within 15-25 min.
      Sham-operated mice, enoxaparin- and ticagrelor-pretreated wild-type and P2Y(12-/
      ) mice developed only small thrombi. After injection of the contrast agent,
      growing thrombi were delineated clearly as negative contrast on CEUS. Thrombus
      size on CEUS after 25 min was significantly smaller in enoxaparin- (0.3 +/- 0.1
      mm(2)) and ticagrelor-treated (0.5 +/- 0.1 mm(2)) wild-type and in P2Y(12-/-)
      mice (0.4 +/- 0.1 mm(2)) as compared with vehicle-treated wild-type mice (2.0 +/-
      0.3 mm(2)) in the maximal sagittal plane (P < 0.001, n = 5-10). CEUS-derived
      thrombus size correlated linearly with thrombus weight and also reflected the
      extent of ligation-induced DVT. CONCLUSIONS: Contrast-enhanced ultrasound allowed
      the real-time quantification of DVT in living mice. Genetic and pharmacologic
      antithrombotic interventions were well reflected by CEUS and suggested an
      important role of the platelet P2Y(12) receptor in early DVT formation.

PMID- 23551897
TI  - Cell adhesion, multicellular morphology, and magnetosome distribution in the
      multicellular magnetotactic prokaryote Candidatus Magnetoglobus multicellularis.
AB  - Candidatus Magnetoglobus multicellularis is an uncultured magnetotactic
      multicellular prokaryote composed of 17-40 Gram-negative cells that are capable
      of synthesizing organelles known as magnetosomes. The magnetosomes of Ca. M.
      multicellularis are composed of greigite and are organized in chains that are
      responsible for the microorganism's orientation along magnetic field lines. The
      characteristics of the microorganism, including its multicellular life cycle,
      magnetic field orientation, and swimming behavior, and the lack of viability of
      individual cells detached from the whole assembly, are considered strong evidence
      for the existence of a unique multicellular life cycle among prokaryotes. It has
      been proposed that the position of each cell within the aggregate is fundamental
      for the maintenance of its distinctive morphology and magnetic field orientation.
      However, the cellular organization of the whole organism has never been studied
      in detail. Here, we investigated the magnetosome organization within a cell, its
      distribution within the microorganism, and the intercellular relationships that
      might be responsible for maintaining the cells in the proper position within the
      microorganism, which is essential for determining the magnetic properties of Ca.
      M. multicellularis during its life cycle. The results indicate that cellular
      interactions are essential for the determination of individual cell shape and the
      magnetic properties of the organism and are likely directly associated with the
      morphological changes that occur during the multicellular life cycle of this
      species.

PMID- 23551898
TI  - Clinical experience of modified diffusion-weighted imaging protocol for lesion
      detection in transient global amnesia: an 8-year large-scale clinical study.
AB  - BACKGROUND AND PURPOSE: The detection rate of typical transient global amnesia
      (TGA) lesions on diffusion-weighted imaging (DWI) can be improved, up to 85% with
      optimal DWI parameters and imaging time. There is limited evidence that these
      findings are similar to those observed in large-scale consecutive patients with
      TGA in clinical practice. METHODS: Patients with clinically diagnosed TGA
      underwent magnetic resonance imaging studies, consecutively, with three sets of
      DWI parameters (standard clinical DWI protocols, the TGA DWI protocol I and the
      TGA DWI protocol II) in which the resolution, slice thickness, and the time
      interval between symptom onset of DWI were varied over an 8-year period. RESULTS:
      TGA lesion detection rates were up to 88% with a modified TGA DWI protocol. The
      lesion detection rate was the highest using TGA DWI protocol I, with b = 3,000
      s/mm(2), a slice thickness of 3 mm, and performed on the third day after symptom
      onset, and TGA DWI protocol II, with b = 2,000 s/mm(2) and a slice thickness of 2
      mm. CONCLUSIONS: A modified TGA DWI protocols for detecting TGA lesions are
      useful in large-scale clinical practice for confirming the diagnosis of TGA
      patients with clinical findings.

PMID- 23551899
TI  - MicroCT analysis of a retrieved root restored with a bonded fiber-reinforced
      composite dowel: a pilot study.
AB  - PURPOSE: This evaluation aimed to (1) validate micro-computed tomography
      (microCT) findings using scanning electron microscopy (SEM) imaging, and (2)
      quantify the volume of voids and the bonded surface area resulting from fiber
      reinforced composite (FRC) dowel cementation technique using microCT scanning
      technology/3D reconstructing software. MATERIALS AND METHODS: A fiberglass dowel
      was cemented in a condemned maxillary lateral incisor prior to its extraction. A
      microCT scan was performed of the extracted tooth creating a large volume of data
      in DICOM format. This set of images was imported to image-processing software to
      inspect the internal architecture of structures. RESULTS: The outer surface and
      the spatial relationship of dentin, FRC dowel, cement layer, and voids were
      reconstructed. Three-dimensional spatial architecture of structures and
      volumetric analysis revealed that 9.89% of the resin cement was composed of voids
      and that the bonded area between root dentin and cement was 60.63% larger than
      that between cement and FRC dowel. CONCLUSIONS: SEM imaging demonstrated the
      presence of voids similarly observed using microCT technology (aim 1). MicroCT
      technology was able to nondestructively measure the volume of voids within the
      cement layer and the bonded surface area at the root/cement/FRC interfaces (aim
      2). CLINICAL SIGNIFICANCE: The interfaces at the root dentin/cement/dowel
      represent a timely and relevant topic where several efforts have been conducted
      in the past few years to understand their inherent features. MicroCT technology
      combined with 3D reconstruction allows for not only inspecting the internal
      arrangement rendered by fiberglass adhesively bonded to root dentin, but also
      estimating the volume of voids and contacted bond area between the dentin and
      cement layer.

PMID- 23551900
TI  - A comparison of insulin detemir and neutral protamine Hagedorn (isophane) insulin
      in the treatment of diabetes: a systematic review.
AB  - The aim of this review is to summarize the clinical efficacy, tolerability and
      safety data of insulin detemir, and compare its use with that of neutral
      protamine Hagedorn (NPH) insulin in randomized controlled trials in people with
      type 1 or type 2 diabetes. A literature search was conducted with PubMed using
      predefined search terms. Studies were included if they met the following
      criteria: randomized, controlled trial, comparison of insulin detemir with NPH
      insulin, non-hospitalized adults aged >=18 years with either type 1 or type 2
      diabetes, and study duration of >=12 weeks. The following types of studies were
      excluded: non-randomized controlled trials, studies of mixed cohorts of patients
      with type 1 or type 2 diabetes that did not report results separately,
      pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or
      health-economic analyses. Fourteen publications met the inclusion criteria. Nine
      studies in people with type 1 diabetes and three studies in people with type 2
      diabetes, using insulin detemir in a basal-bolus regimen were included. Two
      studies were in people with type 2 diabetes using insulin detemir with oral
      antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes,
      insulin detemir treatment provided similar or better glycaemic control, lower
      within-subject variability, similar or lower frequency of hypoglycaemia and less
      weight gain when compared with NPH insulin.

PMID- 23551901
TI  - Towards the characterization and validation of alcohol use disorder subtypes:
      integrating consumption and symptom data.
AB  - BACKGROUND: There is evidence that measures of alcohol consumption, dependence
      and abuse are valid indicators of qualitatively different subtypes of alcohol
      involvement yet also fall along a continuum. The present study attempts to
      resolve the extent to which variations in alcohol involvement reflect a
      difference in kind versus a difference in degree. METHOD: Data were taken from
      the 2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions.
      The sample (51% male; 72% white/non-Hispanic) included respondents reporting past
      12-month drinking at both waves (wave 1: n = 33644; wave 2: n = 25186). We
      compared factor mixture models (FMMs), a hybrid of common factor analysis (FA)
      and latent class analysis (LCA), against FA and LCA models using past 12-month
      alcohol use disorder (AUD) criteria and five indicators of alcohol consumption
      reflecting frequency and heaviness of drinking. RESULTS: Model comparison
      revealed that the best-fitting model at wave 1 was a one-factor four-class FMM,
      with classes primarily varying across dependence and consumption indices. The
      model was replicated using wave 2 data, and validated against AUD and dependence
      diagnoses. Class stability from waves 1 to 2 was moderate, with greatest
      agreement for the infrequent drinking class. Within-class associations in the
      underlying latent factor also revealed modest agreement over time. CONCLUSIONS:
      There is evidence that alcohol involvement can be considered both categorical and
      continuous, with responses reduced to four patterns that quantitatively vary
      along a single dimension. Nosologists may consider hybrid approaches involving
      groups that vary in pattern of consumption and dependence symptomatology as well
      as variation of severity within group.

PMID- 23551902
TI  - COX-2-10aa-PGIS gene therapy improves erectile function in rats after cavernous
      nerve injury.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a very common complication after
      radical prostatectomy. COX-2-10aa-PGIS is a newly engineered protein with COX-2
      and prostacyclin synthase activities that converts arachidonic acid directly to
      prostacyclin (prostaglandin I2 [PGI2]). PGI2 is a potent smooth muscle relaxant.
      AIM: The purpose of this study was to explore the effect and mechanism of COX-2
      10aa-PGIS gene therapy in penile rehabilitation. METHODS: Bilateral cavernous
      nerve crush (BCNC) in adult Sprague-Dawley rats was used to mimic radical
      prostatectomy-induced ED. Sprague-Dawley rats were randomly assigned into four
      groups: 1. sham surgery; 2. BCNC; 3. BCNC + null control recombinant adenovirus
      intracavernous injection; and 4. BCNC + Ad-COX2-10aa-PGIS intracavernous
      injection. Twenty-eight days later, intracavernosal pressure (ICP) was recorded
      under cavernous nerve stimulation; in the meantime, the mean arterial pressure
      (MAP) was monitored. At the end of the measurement, the penis was harvested and
      processed for (i) immunohistochemistry analysis of endothelial nitric oxide
      synthase (eNOS), alpha-smooth muscle actin (alpha-SMA), and transforming growth
      factor beta-1 (TGF-beta1); (ii) Masson's trichrome stain for smooth
      muscle/collagen ratios; (iii) Western blot of eNOS, alpha-SMA, TGF-beta1, and
      COX2-10aa-PGIS; and (iv) terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) assay for apoptosis. MAIN OUTCOME MEASURES: Erectile function
      was evaluated by ICP/MAP. Smooth muscle and endothelium functions in corpora
      cavernosum were assessed by Masson's trichrome stain, immunohistochemistry, and
      Western blot. Apoptosis was identified by TUNEL assay. RESULTS: The results were
      the following: 1. COX2-10aa-PGIS gene therapy improved erectile function (82%,
      compared with control) in the BCNC rat model; 2. COX2-10aa-PGIS gene therapy
      increased eNOS (121%) and alpha-SMA (118%) expression and decreased TGF-beta1
      (45%) expression; 3. COX2-10aa-PGIS gene therapy reduced cell apoptosis after
      cavernous nerve injury (64%); and 4. COX2-10aa-PGIS gene therapy improved smooth
      muscle/collagen ratios (81%). CONCLUSION: Our data demonstrated that COX2-10aa
      PGIS improved erectile function after cavernous nerve injury through antifibrotic
      and anti-apoptotic mechanisms.

PMID- 23551904
TI  - Worldwide transmission and seasonal variation of pandemic influenza A(H1N1)2009
      virus activity during the 2009-2010 pandemic.
AB  - BACKGROUND: Seasonal influenza activity varies with geography and time of year.
      OBJECTIVE: To describe how pandemic influenza A(H1N1)2009 [A(H1N1)pdm09] activity
      varied during the 2009-2010 pandemic. METHODS: We analyzed influenza virological
      data compiled by the World Health Organization from June 2009-August 2010. We
      calculated weekly proportions of A(H1N1)pdm09-positive specimens out of all
      A(H1N1)pdm09-positive specimens detected during the study period for each
      country. We compared parameters of pandemic activity (e.g., peak A[H1N1]pdm09
      weekly proportion [peak activity], number of weeks between the 5th and 95th
      percentiles of A(H1N1)pdm09 cumulative weekly proportion [duration of activity])
      between countries in temperate and tropical-subtropical regions. We quantified
      the proportion of A(H1N1)pdm09 out of all influenza A specimens by country and
      correlated it with countries' central latitudes. RESULTS: We analyzed data from
      80 countries (47 temperate, 33 tropical-subtropical). The median proportion of
      cases identified during the peak week was higher in temperate (0.12) than in
      tropical-subtropical (0.09) regions (P<0.01). The median duration of activity was
      longer in tropical-subtropical (27 weeks) than in temperate countries (20 weeks)
      (P < 0.01). In most temperate countries (98%), peak pandemic activity occurred
      during the fall-winter period. There was a positive correlation between country
      central latitude and proportion of A(H1N1)pdm09 out of all influenza A specimens
      (r: 0.76; P<0.01). CONCLUSIONS: The transmission of A(H1N1)pdm09 exhibited
      similarities with seasonal influenza transmission in that activity varied between
      temperate and tropical-subtropical countries and by time of year. Our findings
      suggest the potential utility of accounting for these factors during future
      pandemic planning.

PMID- 23551903
TI  - Proteasome inhibitor MG-132 induces MCPIP1 expression.
AB  - The proteasome is a protein complex responsible for the degradation of
      polyubiquitin-tagged proteins. Besides the removal of target proteins, the
      proteasome also participates in the regulation of gene transcription in both
      proteolytic and non-proteolytic fashion. In this study the effect of proteasome
      inhibition on the basal expression of monocyte chemotactic protein-1 induced
      protein 1 (MCPIP1) was examined. Treatment of HepG2 or HeLa cells with proteasome
      inhibitor MG-132 resulted in a significant increase of MCPIP1 expression, both at
      mRNA and protein level. Interestingly, MG-132 did not alter MCPIP1 stability.
      Instead, the observed protein increase was blocked by actinomycin D, suggesting
      the involvement of de novo mRNA synthesis in the increase of MCPIP1 protein
      following MG-132 treatment. Using several inhibitors we determined the
      participation of extracellular-signal-regulated kinase 1/2 and p38 kinases in
      MCPIP1 upregulation by MG-132. Our findings show for the first time the impact of
      proteasome inhibition on MCPIP1 protein expression by modulation of the activity
      of intracellular signaling pathways. Overexpression of MCPIP1-myc protein
      decreased the viability of HeLa cells but not HepG2 cells, which correlates with
      the increased susceptibility of HeLa cells to MG-132 toxicity. Notably, both MG
      132 treatment and MCPIP1-myc overexpression led to the activation of apoptosis,
      as revealed by the induction of caspases 3/7 in both types of cell lines. This
      suggests the involvement of MCPIP1 upregulation in toxic properties of proteasome
      inhibition, which is an acknowledged approach to the treatment of several cancer
      types.

PMID- 23551905
TI  - Ay allele promotes azoxymethane-induced colorectal carcinogenesis by macrophage
      migration in hyperlipidemic/diabetic KK mice.
AB  - The incidence of colorectal cancer has been increasing and is associated with
      obesity and diabetes. We have found that type 2 diabetes model KK-Ay/TaJcl (KK
      Ay) mice develop tumors within a short period after treatment with azoxymethane
      (AOM). However, factors that contribute to the promotion of carcinogenesis have
      not been clarified. Therefore, we looked at the genetic background of KK-Ay,
      including two genetic characteristics of KK/TaJcl (KK) mice and C57BL/6J-Ham-Ay/+
      (Ay) mice, compared with other non-obese and non-diabetic mouse strains C57BL/6J
      and ICR, and induced colorectal premalignant lesions, aberrant crypt foci (ACF),
      and tumors using AOM (150 MUg/mouse/week for 4 weeks and 200 MUg/mouse/week for 6
      weeks, respectively). The mice with a diabetes feature, KK-Ay and KK, developed
      significantly more ACF, 67 and 61 per mouse, respectively, whereas ICR, Ay, and
      C57BL/6J mice developed 42, 24, and 18 ACF/mouse, respectively, at 17 weeks of
      age. Serum insulin and triglyceride levels in KK-Ay and KK mice were quite high
      compared with other non-diabetic mouse strains. Interestingly, KK-Ay mice
      developed more colorectal tumors (2.7 +/- 2.3 tumor/mouse) than KK mice (1.2 +/-
      1.1 tumor/mouse) at 25 weeks of age, in spite of similar diabetic conditions. The
      colon cancers that developed in both KK-Ay and KK mice showed similar activation
      of beta-catenin signaling. However, mRNA levels of inflammatory factors related
      to the activation of macrophages were significantly higher in colorectal cancer
      of KK-Ay mice than in KK. These data indicate that factors such as insulin
      resistance and dyslipidemia observed in obese and diabetic patients could be
      involved in susceptibility to colorectal carcinogenesis. In addition, increase of
      tumor-associated macrophages may play important roles in the stages of promotion
      of colorectal cancer.

PMID- 23551906
TI  - Pediatric cardiopulmonary arrest in the postanesthesia care unit: analysis of
      data from the American Heart Association Get With The Guidelines-Resuscitation
      registry.
AB  - BACKGROUND: Nearly 20% of anesthesia-related pediatric cardiopulmonary arrests
      (CPAs) occur during emergence or recovery. The aims of this study were to
      describe (i) the nature of pediatric postanesthesia care unit (PACU) CPA and
      subsequent outcomes and (ii) factors associated with mortality. METHODS:
      Cardiopulmonary Arrests occurring in PACU in children (<18 years) were identified
      from the American Heart Association Get With The Guidelines-Resuscitation,
      multicenter CPA registry. Demographics, underlying conditions, cause(s) of CPA,
      monitoring, interventions and outcomes were extracted. Descriptive statistics
      were used to characterize data, and odds ratios (OR) with confidence intervals
      (CI) were calculated as appropriate to compare survivors and nonsurvivors.
      RESULTS: Twenty seven CPA events were included: 67% in children <5 years and 30%
      in infants (<1 year). Most children (78%) had underlying comorbidities, including
      15% with congenital heart disease. Respiratory issues were the most frequent
      causes of CPA (44%), but cardiac/hemodynamic causes were associated with
      nonsurvival (P = 0.01). Nonsurvival was also associated with older age (P =
      0.02), weekend occurrence (P < 0.01), nonpediatric setting (P = 0.02) and
      occurrence at night (P = 0.04). CONCLUSIONS: This study identified similar risk
      factors and underlying causes as described in previous reports of pediatric
      perioperative CPA, with higher mortality following a cardiac/hemodynamic cause.

PMID- 23551907
TI  - Neuropsychological correlates of complicated grief in older spousally bereaved
      adults.
AB  - OBJECTIVES: Across many research domains, evidence for complicated grief as a
      distinct psychopathology continues to grow. Previous research from
      neuropsychology has shown an increased attentional bias to emotionally relevant
      stimuli in those suffering from complicated grief. This study furthers our
      understanding of the characteristics that distinguish complicated grief. We
      expand on previous research by (a) testing older adults, (b) excluding those with
      comorbid major depressive disorder, (c) using participant-chosen grief-related
      stimuli, and (d) using a married, nonbereaved control group. METHODS: We
      recruited 76 older adults in 3 groups: spousally bereaved with complicated grief,
      spousally bereaved with noncomplicated grief, and nonbereaved controls.
      Performance on the Wisconsin Card Sorting Task, Digit Span Backwards, and the
      emotional counting Stroop was examined. RESULTS: Results indicate longer reaction
      time across 3 blocks of grief-related words in the complicated grief group but no
      difference across 3 blocks of the neutral words. The 3 groups performed
      comparably on the other neurocognitive tasks, indicating no cognitive differences
      in working memory or set shifting between groups. Furthermore, these effects of
      complicated grief generalize to older adults and appear independent of major
      depression. DISCUSSION: Complicated grief has cognitive interference as a
      neuropsychological component highlighting it as distinct from noncomplicated
      grief.

PMID- 23551908
TI  - Prokaryote-expressed M2e protein improves H9N2 influenza vaccine efficacy and
      protection against lethal influenza A virus in mice.
AB  - BACKGROUND: Influenza vaccines are prepared annually based on global
      epidemiological surveillance data. However, since there is no method by which to
      predict the influenza strain that will cause the next pandemic, the demand to
      develop new vaccination strategies with broad cross-reactivity against influenza
      viruses are clearly important. The ectodomain of the influenza M2 protein (M2e)
      is an attractive target for developing a vaccine with broad cross-reactivity. For
      these reasons, we investigated the efficacy of an inactivated H9N2 virus vaccine
      (a-H9N2) mixed with M2e (1xM2e or 4xM2e) proteins expressed in Escherichia coli,
      which contains the consensus of sequence the extracellular domain of matrix 2
      (M2e) of A/chicken/Vietnam/27262/09 (H5N1) avian influenza virus, and
      investigated its humoral immune response and cross-protection against influenza A
      viruses. RESULTS: Mice were intramuscularly immunized with a-H9N2, 1xM2e alone,
      4xM2e alone, a-H9N2/1xM2e, or a-H9N2/4xM2e. Three weeks post-vaccination, mice
      were challenged with lethal homologous (A/ chicken /Korea/ma163/04, H9N2) or
      heterosubtypic virus (A/Philippines/2/82, H3N2 and A/aquatic bird/Korea/maW81/05,
      H5N2). Our studies demonstrate that the survival of mice immunized with a
      H9N2/1xM2e or with a-H9N2/4xM2e (100% survival) was significantly higher than
      that of mouse-adapted H9N2 virus-infected mice vaccinated with 1xM2e alone or
      with 4xM2e alone (0% survival). We also evaluated the protective efficacy of the
      M2e + vaccine against infection with mouse-adapted H5N2 influenza virus.
      Protection from death in the control group (0% survival) was similar to that of
      the 1*M2e alone and 4xM2e alone-vaccinated groups (0% survival). Only 40% of mice
      vaccinated with vaccine alone survived challenge with H5N2, while the a
      H9N2/1*M2e and a-H9N2/4*M2e groups showed 80% and 100% survival following mouse
      adapted H5N2 challenge, respectively. We also examined cross-protection against
      human H3N2 virus and found that the a-H9N2/1*M2e group displayed partial cross
      protection against H3N2 (40% survival), whereas vaccine alone, 1*M2e alone, 4*M2e
      alone, or H9N2/1*M2e groups showed incomplete protection (0% survival) in
      response to challenge with a lethal dose of human H3N2 virus. CONCLUSIONS: Taken
      together, these results suggest that prokaryote-expressed M2e protein improved
      inactivated H9N2 virus vaccine efficacy and achieved cross-protection against
      lethal influenza A virus infection in mice.

PMID- 23551910
TI  - Unusual presentation of acute otomastoiditis with petrositis.
AB  - The anatomical relationships of the middle ear, the mastoid air cells, the
      temporal bone and intracranial structures can lead to invasive infections. Acute
      mastoiditis is the most common intratemporal complication of acute otitis media.
      Timely management includes antimicrobial therapy, imaging including ultrasound
      and/or computed tomography, surgical consultation and intervention. There are
      insufficient data to provide an evidence-based diagnostic tool for acute
      mastoiditis. Clinical, laboratory and microbiological differences between
      children with simple and complicated mastoiditis will be explored after case
      presentation of a 5-year-old boy with fever and a tender, soft-tissue swelling
      over the left zygomatic arch. 

PMID- 23551909
TI  - A survey of access to trial of labor in California hospitals in 2012.
AB  - BACKGROUND: In 2010, the NIH and ACOG recommended increasing women's access to
      trial of labor after cesarean (TOLAC). This study explored access to TOLAC in
      California, change in access since 2007 and 2010, and characteristics of TOLAC
      and non-TOLAC hospitals. METHODS: Between November 2011 and June 2012, charge
      nurses at all civilian California birth hospitals were surveyed about hospitals'
      TOLAC availability and requirements for providers. VBAC rates were obtained from
      the California Office of Statewide Health Planning and Development (OSHPD).
      Distance between hospitals was calculated using OSHPD geocoding. RESULTS: All 243
      birth hospitals that were contacted participated. In 2010, among the 56% TOLAC
      hospitals, the median VBAC rate among TOLAC hospitals was 10.8% (range 0-37.3%).
      The most cited reason for low VBAC rates was physician unwillingness to perform
      them, especially due to the requirement to be continually present during labor.
      TOLAC hospitals were more likely to be larger hospitals in urban communities with
      obstetrical residency training. However, there were six (11.3%) residency
      programs in non-TOLAC hospitals and 5 (13.5%) rural hospitals offering TOLAC. The
      majority of TOLAC hospitals had 24/7 anesthesia coverage and required the
      obstetrician to be continually present if a TOLAC patient was admitted; 17
      (12.2%) allowed personnel to be 15-30 minutes away. TOLAC eligibility criteria
      included one prior cesarean (32.4%), spontaneous labor (52.5%), continuous fetal
      monitoring and intravenous access (99.3%), and epidural analgesia (19.4%). The
      mean distance from a non-TOLAC to a TOLAC hospital was 37 mi. with 25% of non
      TOLAC hospitals more than 51 mi. from the closest TOLAC hospital. In 2012, 139
      hospitals (57.2%) offered TOLAC, 16.6% fewer than in 2007. Since 2010, five
      hospitals started and four stopped offering TOLAC, a net gain of one hospital
      offering TOLAC with three more considering it. Only two hospitals cited change in
      ACOG guidelines as a reason for the change. CONCLUSIONS: Despite the 2010 NIH and
      ACOG recommendations encouraging greater access to TOLAC, 44% of California
      hospitals do not allow TOLAC. Of the 56% allowing TOLAC, 10.8% report fewer than
      3% VBAC births. Thus, national recommendations encouraging greater access to
      TOLAC had a minor effect in California.

PMID- 23551911
TI  - Utility of controlled attenuation parameter measurement for assessing liver
      steatosis in Japanese patients with chronic liver diseases.
AB  - AIM: Steatosis is a common histological feature of chronic liver disease,
      especially alcoholic and non-alcoholic fatty liver disease, as well as chronic
      hepatitis C. A recent study showed that evaluating the controlled attenuation
      parameter (CAP) with transient elastography was an efficient way of non
      invasively determining the severity of hepatic steatosis. The objective of this
      study was to prospectively evaluate the utility of CAP for diagnosing steatosis
      in patients with chronic liver disease. METHODS: One hundred and fifty-five
      consecutive patients with suspected chronic liver disease underwent steatosis
      diagnosis using CAP, blood sample analyses, computed tomography for assessing the
      liver/spleen ratio and liver biopsy. Steatosis was graded according to the
      percentage of fat-containing hepatocytes: S0, less than 5%; S1, 5-33%; S2, 34
      66%; and S3: more than 66%. RESULTS: The CAP was significantly correlated with
      steatosis grade, and there were significant differences between the CAP value of
      the S0 patients and those of the patients with other grades of steatosis. S0 and
      S1-3 hepatic steatosis were considered to represent mild and significant
      steatosis, respectively. The CAP values of the patients with mild and significant
      steatosis were significantly different (P < 0.0001). The area under the receiver
      operator curve (AUROC) value of the CAP for diagnosing significant steatosis was
      0.878 (95% confidence interval, 0.818-0.939), and the optimal CAP cut-off value
      for detecting significant steatosis was 232.5 db/m. In multivariate analysis, the
      CAP (P = 0.0002) and the liver to spleen ratio (P = 0.004) were found to be
      significantly associated with significant steatosis. CONCLUSION: The CAP is a
      promising tool for rapidly and non-invasively diagnosing steatosis.

PMID- 23551912
TI  - Age-related degeneration of the egg-laying system promotes matricidal hatching in
      Caenorhabditis elegans.
AB  - The identification and characterization of age-related degenerative changes is a
      critical goal because it can elucidate mechanisms of aging biology and contribute
      to understanding interventions that promote longevity. Here, we document a novel,
      age-related degenerative change in C. elegans hermaphrodites, an important model
      system for the genetic analysis of longevity. Matricidal hatching--intra-uterine
      hatching of progeny that causes maternal death--displayed an age-related increase
      in frequency and affected ~70% of mated, wild-type hermaphrodites. The timing and
      incidence of matricidal hatching were largely independent of the levels of early
      and total progeny production and the duration of male exposure. Thus, matricidal
      hatching appears to reflect intrinsic age-related degeneration of the egg-laying
      system rather than use-dependent damage accumulation. Consistent with this model,
      mutations that extend longevity by causing dietary restriction significantly
      delayed matricidal hatching, indicating age-related degeneration of the egg
      laying system is controlled by nutrient availability. To identify the underlying
      tissue defect, we analyzed serotonin signaling that triggers vulval muscle
      contractions. Mated hermaphrodites displayed an age-related decline in the
      ability to lay eggs in response to exogenous serotonin, indicating that vulval
      muscles and/or a further downstream function that is necessary for egg laying
      degenerate in an age-related manner. By characterizing a new, age-related
      degenerative event displayed by C. elegans hermaphrodites, these studies
      contribute to understanding a frequent cause of death in mated hermaphrodites and
      establish a model of age-related reproductive complications that may be relevant
      to the birthing process in other animals such as humans.

PMID- 23551913
TI  - Inter-epidemic and between-season persistence of rift valley fever: vertical
      transmission or cryptic cycling?
AB  - Rift Valley fever (RVF) is an emerging zoonotic mosquito-borne infectious disease
      that has been identified as a risk for spread to other continents and can cause
      mass livestock mortality. In equatorial Africa, outbreaks of RVF are associated
      with high rainfall, when vector populations are at their highest. It is, however,
      unclear how RVF virus persists during the inter-epidemic periods and between
      seasons. Understanding inter-epidemic persistence as well as the role of vectors
      and hosts is paramount to creating effective management programmes for RVF
      control. We created a mathematical model for the spread of RVF and used the model
      to explore different scenarios of persistence including vertical transmission and
      alternate wildlife hosts, with a case study on buffalo in Kruger National Park,
      South Africa. Our results suggest that RVF persistence is a delicate balance
      between numerous species of susceptible hosts, mosquito species, vertical
      transmission and environmental stochasticity. Further investigations should not
      focus on a single species, but should instead consider a myriad of susceptible
      host species when seeking to understand disease dynamics. 

PMID- 23551915
TI  - Temperature-size relations from the cellular-genomic perspective.
AB  - A family of empirically based ecological 'rules', collectively known as
      temperature-size rules, predicts larger body size in colder environments. This
      prediction is based on studies demonstrating that a wide range of ectotherms show
      increased body size, cell size or genome size in low-temperature habitats, or
      that individuals raised at low temperature become larger than conspecifics raised
      at higher temperature. There is thus a potential for reduction in size with
      global warming, affecting all levels from cell volume to body size, community
      composition and food webs. Increased body size may be obtained either by
      increasing the size or number of cells. Processes leading to changed cell size
      are of great interest from an ecological, physiological and evolutionary
      perspective. Cell size scales with fundamental properties such as genome size,
      growth rate, protein synthesis rates and metabolic activity, although the causal
      directions of these correlations are not clear. Changes in genome size will thus,
      in many cases, not only affect cell or body size, but also life-cycle strategies.
      Symmetrically, evolutionary drivers of life-history strategies may impact growth
      rate and thus cell size, genome size and metabolic rates. Although this goes to
      the core of many ecological processes, it is hard to move from correlations to
      causations. To the extent that temperature-driven changes in genome size result
      in significant differences among populations in body size, allometry or life
      cycle events such as mating season, it could serve as a fast route to speciation.
      We offer here a novel perspective on the temperature-size rules from a 'bottom
      up' perspective: how temperature may induce changes in genome size, and thus
      implicitly in cell size and body size of metazoans. Alternatively: how
      temperature-driven enlargement of cells also dictates genome-size expansion to
      maintain the genome-size to cell-volume ratio. We then discuss the different
      evolutionary drivers in aquatic versus terrestrial systems, and whether it is
      possible to arrive at a unifying theory that also may serve as a predictive tool
      related to temperature changes. This, we believe, will offer an updated review of
      a basic concept in ecology, and novel perspectives on the basic biological
      responses to temperature changes from a genomic perspective.

PMID- 23551914
TI  - Depressive symptoms and metabolic markers of risk for type 2 diabetes in obese
      adolescents.
AB  - OBJECTIVE: Although higher rates of depression are found among individuals with
      type 2 diabetes, it remains unknown if the presence of depressive symptoms is
      associated with heightened metabolic risk for the development of type 2 diabetes
      among youth. The objective of this study was to evaluate whether depressive
      symptoms in obese adolescents are associated with impaired beta-cell function
      relative to insulin sensitivity [oral disposition index (oDI)] and/or dysglycemia
      or prediabetes, predictors of type 2 diabetes development. RESEARCH DESIGN AND
      METHODS: Fasting and oral glucose tolerance test (OGTT)-derived indices of
      glucose tolerance, insulin sensitivity, secretion, and oDI were evaluated in
      obese youth (n = 56, age 15.0 +/- 1.6 yr, 68% female). The Children's Depression
      Inventory was utilized to determine depressive symptomatology. RESULTS: Despite
      no association between depressive symptoms and measures of adiposity, youth with
      higher depressive symptoms had (i) significantly higher fasting and stimulated
      glucose levels (13% higher glucose area under the OGTT curve), (ii) ~50% lower
      oDI, and (iii) a 50% frequency of prediabetes. CONCLUSIONS: These data point to
      an important relationship between depressive symptoms and a heightened metabolic
      risk for type 2 diabetes in obese adolescents, including prediabetes and
      impairment in beta-cell function relative to insulin sensitivity. While the
      directionality of these relationships is unknown, it should be determined if
      treating one disorder improves the other or vice versa.

PMID- 23551916
TI  - Bone marrow non-mesenchymal mononuclear cells induce functional differentiation
      of neuroblastoma cells.
AB  - Less is known about the non-mesenchymal mononuclear cell fraction of human bone
      marrow on functional adaptation of neuroblastoma cells. Using
      immunocytochemistry, we showed that bone-marrow mononuclear cell (BMMC)
      conditioned medium can induce tyrosine hydroxylase expression in neuroblastoma
      cells, which is similar to the effect of retinoic acid. Using quantitative RT
      PCR, we showed that NGF, CNTF, and BDNF mRNAs were detected in unfractionated
      BMMC populations from all human donors at different expression levels. Our
      results suggest that cells of the non-mesenchymal mononuclear cell fraction can
      induce functional adaptation of neuroblastoma cells, probably via their secreted
      trophic factors.

PMID- 23551917
TI  - Factors other than root resorption may result in root shortening.

PMID- 23551918
TI  - Assessment of individual dose utilization vs. physician prescribing
      recommendations for recombinant activated factor VII (rFVIIa) in paediatric and
      adult patients with congenital haemophilia and alloantibody inhibitors (CHwI):
      the Dosing Observational Study in Hemophilia (DOSE).
AB  - Recent data from the Dosing Observational Study in Hemophilia diary study has
      described home treatment with recombinant activated factor VII (rFVIIa) in
      congenital haemophilia with inhibitors (CHwI). The current analysis compares
      prescribed and patient/caregiver-reported rFVIIa administration in paediatric and
      adult CHwI patients in this study. Patients with >= 4 bleeding episodes within a
      3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were
      eligible. Patients/caregivers completed a diary for >= 90 days or until the
      patient experienced four bleeds. Initial, total and mean rFVIIa doses reported
      for each bleeding episode were calculated and compared with the physician
      prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%)
      completed the study. Children and adults had similar mean durations of bleeding
      episodes. Both patient groups were administered higher initial rFVIIa doses for
      joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs.
      200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs.
      123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint
      bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but
      children received significantly more doses per joint bleed than adults (median
      6.5 vs. 3.0). The median total dose per joint bleed was higher in children than
      adults (1248.7 vs. 441.6). For children and adults, both initial and additional
      doses administered for bleeds were higher than prescribed. Children received
      higher total doses per bleed due to an increased number of infusions per bleed.

PMID- 23551919
TI  - Comparison of amino acid metabolism in frozen-thawed and fresh early-stage human
      embryos.
AB  - AIMS: To compare the amino acid differences of changes of frozen-thawed early
      stage human embryos and fresh cultured early-stage human embryos. MATERIAL AND
      METHODS: Discarded embryos and their in vitro culture medium of patients who
      underwent in vitro fertilization-embryo transfer (IVF-ET) at the Research Center
      for Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen
      University, from September 2010 to April 2011 were collected. Amino acid levels
      were determined by high performance liquid chromatography. RESULTS: The amino
      acid differences of changes in the culture medium of fresh embryos (661.50
      MUmol/L) were significantly higher than in the medium of post-thawed embryos
      (232.00 MUmol/L) at 0.5 h (P < 0.001). At 1 and 2 h, no significant difference of
      change was found in all amino acids. Differences in the concentration of amino
      acids between post-thawed embryos and blank control medium were already present
      beginning at 1 h. CONCLUSIONS: The level of amino acid metabolism of frozen
      thawed early-stage human embryos has already recovered from the state of
      metabolic stagnation during cryopreservation at 1 h of incubation after thawing,
      and the amino acid metabolism level at that time approximates that in fresh
      embryos before freezing. This may be established as the optimal embryo transfer
      time in IVF-ET.

PMID- 23551920
TI  - Comparison of the diagnostic accuracy of five different stool antigen tests for
      the diagnosis of Helicobacter pylori infection.
AB  - BACKGROUND: Several noninvasive diagnostic tests based on the detection of
      Helicobacter pylori stool antigen (HpSA) have been developed. The aim of the
      study was to compare the diagnostic accuracy of 5 HpSA tests-2 monoclonal enzyme
      immunoassay tests (EIAs: the Premier Platinum HpSA Plus test and Helicobacter
      pylori Antigen (Hp Ag) test) and 3 rapid immunochromatographic assay (ICA) tests
      (the ImmunoCard STAT! HpSA test, one step HpSA test, and H. pylori fecal antigen
      test)--for diagnosing H. pylori infection in adult patients with dyspeptic
      symptoms before eradication therapy. MATERIALS AND METHODS: A total of 198
      patients with dyspeptic symptoms were included in the study. A gastric biopsy was
      collected for histopathology and rapid urease testing. Stool specimens for HpSA
      testing were also collected. Patients were considered H. pylori positive if two
      invasive tests (histological and rapid urease tests) were positive. RESULTS: The
      sensitivity and specificity were 92.2% and 94.4%, respectively, for the Premier
      Platinum HpSA Plus test; 48.9% and 88.9%, respectively, for the HP Ag test; 86.7%
      and 88.9, respectively, for the One Step HpSA test; 68.9% and 92.6%,
      respectively, for the ImmunoCard STAT! HpSA test; and 78.9% and 87%,
      respectively, for the H. Pylori fecal antigen test. CONCLUSIONS: The Premier
      Platinum HpSA Plus EIA test was determined to be the most accurate stool test for
      diagnosing H. pylori infections in adult dyspeptic patients. The currently
      available ICA-based tests are fast and easy to use but provide less reliable
      results.

PMID- 23551921
TI  - Multiple layer 5 pyramidal cell subtypes relay cortical feedback from secondary
      to primary motor areas in rats.
AB  - Higher-order motor cortices, such as the secondary motor area (M2) in rodents,
      select future action patterns and transmit them to the primary motor cortex (M1).
      To better understand motor processing, we characterized "top-down" and "bottom
      up" connectivities between M1 and M2 in the rat cortex. Somata of pyramidal cells
      (PCs) in M2 projecting to M1 were distributed in lower layer 2/3 (L2/3) and upper
      layer 5 (L5), whereas PCs projecting from M1 to M2 had somata distributed
      throughout L2/3 and L5. M2 afferents terminated preferentially in upper layer 1
      of M1, which also receives indirect basal ganglia output through afferents from
      the ventral anterior and ventromedial thalamic nuclei. On the other hand, M1
      afferents terminated preferentially in L2/3 of M2, a zone receiving indirect
      cerebellar output through thalamic afferents from the ventrolateral nucleus.
      While L5 corticopontine (CPn) cells with collaterals to the spinal cord did not
      participate in corticocortical projections, CPn cells with collaterals to the
      thalamus contributed preferentially to connections from M2 to M1. L5 callosal
      projection (commissural) cells participated in connectivity between M1 and M2
      bidirectionally. We conclude that the connectivity between M1 and M2 is
      directionally specialized, involving specific PC subtypes that selectively target
      lamina receiving distinct thalamocortical inputs. 

PMID- 23551923
TI  - Sagittal condylar angle and gender differences.
AB  - PURPOSE: The purpose of this study was to measure sagittal condylar inclination
      (SCI) in male and female participants and to assess differences between the two
      groups. This measurement has a clinical value in setting the articulator SCI
      before fabrication of indirect restorations. MATERIALS AND METHODS: The study
      included 32 dental students, 16 men and 16 women (aged 18 to 40 years). The
      participants had no signs of muscular or articular pain. SCI was recorded for
      participants using a CADIAX(r) compact 2 electronic axiograph. RESULTS: The mean
      SCI in both men and women varied between 26.1 degrees  and 61.8 degrees , with a
      mean of 41.9 degrees  (SD 7.8). The mean right SCI was 42.0 degrees  (SD 8.5),
      and the mean left SCI was 41.9 degrees  (SD 9.2). The mean SCI for men was 40.3
      degrees  (SD 7.9), and the mean for women was 43.6 degrees  (SD 7.7). No
      statistically significant difference in SCI values was found between the right
      and left side (p = 0.995), or between the male and female groups (p = 0.133).
      Also, no correlation could be found between SCI and the age of the participants
      (r(2) = 0.016, p = 0.489). CONCLUSIONS: The mean value of SCI was within the
      range reported in previous studies. SCI is highly variable, but this variability
      does not seem to be attributed to condylar asymmetry, gender, or age of the adult
      participants. This high variability suggests that independent condylar
      measurements should be conducted for each patient instead of relying on reported
      average values.

PMID- 23551922
TI  - Structural and functional aspects relating to cost and benefit of rich club
      organization in the human cerebral cortex.
AB  - Recent findings have demonstrated that a small set of highly connected brain
      regions may play a central role in enabling efficient communication between
      cortical regions, together forming a densely interconnected "rich club." However,
      the density and spatial layout of the rich club also suggest that it constitutes
      a costly feature of brain architecture. Here, combining anatomical T1, diffusion
      tensor imaging, magnetic transfer imaging, and functional MRI, several aspects of
      structural and functional connectivity of the brain's rich club were examined.
      Our findings suggest that rich club regions and rich club connections exhibit
      high levels of wiring volume, high levels of white matter organization, high
      levels of metabolic energy usage, long maturational trajectories, more variable
      regional time series, and more inter-regional functional couplings. Taken
      together, these structural and functional measures extend the notion that rich
      club organization represents a high-cost feature of brain architecture that puts
      a significant strain on brain resources. The high cost of the rich club may,
      however, be offset by significant functional benefits that the rich club confers
      to the brain network as a whole. 

PMID- 23551924
TI  - Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial
      agonists: a meta-analysis.
AB  - The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A)
      receptor partial agonists of the azapirone class, which are not antipsychotic,
      have benefits for adjunctive treatment of overall psychopathology, positive and
      negative symptoms for patients with schizophrenia. We carried out a systematic
      review of the literature available through PubMed, Cochrane Library, PsycINFO and
      Google Scholar during September 2012, followed by a meta-analysis of randomized
      placebo-controlled trials. Risk ratio (RR), 95% confidence intervals (CI) and
      standardized mean difference (s.m.d.) were calculated. Four studies, involving
      163 patients with schizophrenia, met inclusion criteria: buspirone: three trials
      and 137 patients; tandospirone: one trial and 26 patients. As adjunctive therapy,
      5-HT1A partial agonists were significantly superior to placebo for overall
      improvement in psychopathology (s.m.d. = -0.46, CI = -0.79 to -0.13, p = 0.006, N
      = 4, n = 149) and marginally more effective to improve positive symptoms (s.m.d.
      = -0.31, CI = -0.64 to 0.01, p = 0.06, N = 4, n = 149). However, 5-HT1A partial
      agonists were not more efficacious than placebo as adjunctive therapy for
      improving negative symptoms (s.m.d. = -0.09, CI = -0.60 to 0.42, p = 0.72, N = 4,
      n = 149). In addition, there was no significant difference in discontinuation
      rates between 5-HT1A partial agonists and placebo (all cause: RR = 0.98, CI =
      0.49-1.98, p = 0.96, N = 4, n = 153, side-effects: RR = 1.96, CI = 0.54-7.19, p =
      0.31, N = 4, n = 153). 5-HT1A partial agonists as adjunctive therapy improved
      overall psychopathology with a trend to improve positive symptoms in patients
      with schizophrenia. Because the number of studies was small, additional
      controlled clinical trials with larger numbers of patients are indicated.

PMID- 23551925
TI  - The once-daily human GLP-1 analogue liraglutide impacts appetite and energy
      intake in patients with type 2 diabetes after short-term treatment.
AB  - The aim was to investigate effects of liraglutide on appetite and energy intake
      in a randomized, placebo-controlled, double-blind, crossover study. Eighteen
      subjects with type 2 diabetes were assigned to treatment with once-daily
      subcutaneous liraglutide (increasing by weekly 0.6 mg increments) or placebo for
      3 weeks. Appetite ratings were assessed using visual analogue scales during a 5-h
      meal test. Energy and macronutrient intake during the subsequent ad libitum lunch
      were also measured. After 3 weeks, mean postprandial and minimum hunger ratings
      were significantly lower with liraglutide 1.8 mg than placebo (p < 0.01), and the
      mean overall appetite score was significantly higher (p = 0.05), indicating
      reduced appetite. Liraglutide was associated with higher maximum fullness ratings
      (p = 0.001) and lower minimum ratings of prospective food consumption (p = 0.01).
      Mean estimated energy intake was 18% lower for liraglutide than placebo
      [estimated ratio 0.82 (95% CI 0.73;0.94); p = 0.004], but no significant
      differences in macronutrient distribution were noted. Findings suggest that
      reduced appetite and energy intake may contribute to liraglutide-induced weight
      loss. 

PMID- 23551926
TI  - Resveratrol and fish oil reduce catecholamine-induced mortality in obese rats:
      role of oxidative stress in the myocardium and aorta.
AB  - The exact mechanisms of the relationship between obesity and cardiovascular
      events are not yet fully understood; however, oxidative stress may be involved.
      Thus, the aim of the present study was to evaluate the effects of resveratrol and
      fish oil on catecholamine-induced mortality in obese rats. To begin with, rats
      were divided into five groups: (1) lean, (2) obese, (3) obese supplemented with
      resveratrol, (4) obese supplemented with fish oil and (5) obese supplemented with
      resveratrol and fish oil (n 18 rats per group), for 2 months. After
      supplementation, the groups were subdivided as with (n 10) and without (n 8)
      cardiovascular catecholaminergic stress after isoproterenol (60 mg/kg) injection.
      At 24 h later, the survival rate was analysed. The obese group showed lower
      survival rates (10 %) when compared with the lean group (70 %). On the other
      hand, resveratrol (50 %) and fish oil (40 %) increased the survival rate of obese
      rats (chi(2) test, P= 0.019). Biochemical analyses of the myocardium and aorta
      revealed that obese rats had higher levels of superoxide and oxidative damage to
      lipids and protein. This was associated with reduced superoxide dismutase and
      glutathione peroxidase activity in both the myocardium and aorta. The
      supplementation increased antioxidant enzyme activities and reduced oxidative
      damage. We also evaluated the nuclear factor-erythroid 2 p45-related factor 2
      (Nrf2)/Kelch-like ECH-associated protein 1 antioxidant pathway. Nrf2 protein
      levels that were reduced in obese rats were increased by the antioxidant
      treatment. Taken together, these results showed that resveratrol and fish oil
      reduce catecholamine-induced mortality in obese rats, partly through the
      reduction of oxidative stress.

PMID- 23551927
TI  - Advanced neuroimaging studies in a patient with brain metastases from
      transitional cell carcinoma of the bladder.
AB  - BACKGROUND AND PURPOSE: The differential diagnosis in single or oligo-brain
      lesions in metastatic cancer patients remains broad. Advanced imaging studies can
      be employed to help refine the differential and potentially guide treatment.
      METHODS: Case report of a 52-year-old male patient with known transitional cell
      carcinoma of the bladder presented with headaches, cognitive symptoms, and
      episodic presyncope. Brain magnetic resonance imaging (MRI), magnetic resonance
      spectroscopy (MRS), and octreotide scans were performed to evaluate the
      underlying etiology of his symptoms. RESULTS: MRI revealed two enhancing mass
      lesions in left temporal and left cerebellar locations. Both lesions were
      octreotide avid and MRS of the temporal lesion showed a single large lipid peak
      at 1.3 ppm, a small NAA peak, and a markedly increased choline:creatine ratio
      that was relatively characteristic for metastases. Pathology from surgical
      resection revealed transitional cell carcinoma of the bladder. CONCLUSIONS:
      Resection of both lesions revealed metastatic transitional cell carcinoma. This
      is the first report of octreotide scan characteristics in a patient with
      transitional cell carcinoma with central nervous system (CNS) metastases. The
      octreotide avidity of these transitional cell CNS metastases suggests the
      presence of somatostatin receptors that may be considered as a potential
      therapeutic target.

PMID- 23551928
TI  - Psychological correlates of sexual dysfunction in female rectal and anal cancer
      survivors: analysis of baseline intervention data.
AB  - INTRODUCTION: Sexual dysfunction represents a complex and multifactorial
      construct that can affect both men and women and has been noted to often
      deteriorate significantly after treatment for rectal and anal cancer. Despite
      this, it remains an understudied, underreported, and undertreated issue in the
      field of cancer survivorship. AIM: This study examined the characteristics of
      women enrolled in an intervention trial to treat sexual dysfunction, and explored
      the relationship between sexual functioning and psychological well-being.
      METHODS: There were 70 female posttreatment anal or rectal cancer survivors
      assessed as part of the current study. Participants were enrolled in a randomized
      intervention trial to treat sexual dysfunction and completed outcome measures
      prior to randomization. MAIN OUTCOMES MEASURES: The main outcome measures are
      quality of life (QOL) (European Organization for Research and Treatment of Cancer
      Core Quality of Life Questionnaire [EORTC-QLQ-C30] and Colorectal Cancer-Specific
      Module [QLQ-CR38]), sexual functioning (Female Sexual Functioning Index), and
      psychological well-being (Brief Symptom Inventory Depression/Anxiety, Impact of
      Events Scale-Revised, CR-38 Body Image). RESULTS: Women enrolled in the study
      intervention were on average 55 years old, predominantly Caucasian (79%), married
      (57%), and a median of 4 years postprimary treatment. For those reporting sexual
      activity at baseline (N=41), sexual dysfunction was associated with a range of
      specific measures of psychological well-being, all in the hypothesized direction.
      The Sexual/Relationship Satisfaction subscale was associated with all measures of
      psychological well-being (r=-0.45 to -0.70, all P<0.01). Body image, anxiety, and
      cancer-specific posttraumatic distress were notable in their association with
      subscales of sexual functioning, while a global QOL measure was largely
      unrelated. CONCLUSIONS: For sexually active female rectal and anal cancer
      survivors enrolled in a sexual health intervention, sexual dysfunction was
      significantly and consistently associated with specific measures of psychological
      well-being, most notably Sexual/Relationship Satisfaction. These results suggest
      that sexual functioning may require focused assessment by providers, beyond broad
      QOL assessments, and that attention to Sexual/Relationship Satisfaction may be
      critical in the development and implementation of interventions for this cohort
      of patients.

PMID- 23551929
TI  - Evaluation of the fluorescent probes Nile Red and 25-NBD-cholesterol as
      substrates for steroid-converting oxidoreductases using pure enzymes and
      microorganisms.
AB  - The fluorescent probes Nile Red (nonsteroidal dye) and 25-{N-[(7-nitrobenz-2-oxa
      1,3-diazol-4-yl)-methyl]amino}-27-norcholesterol (25-NBD-cholesterol) (a
      cholesterol analog) were evaluated as novel substrates for steroid-converting
      oxidoreductases. Docking simulations with autodock showed that Nile Red fits well
      into the substrate-binding site of cytochrome P450 17alpha-hydroxylase/17,20
      lyase (CYP17A1) (binding energy value of -8.3 kcal.mol-1). Recombinant
      Saccharomyces cerevisiae and Yarrowia lipolytica, both expressing CYP17A1, were
      found to catalyze the conversion of Nile Red into two N-dealkylated derivatives.
      The conversion by the yeasts was shown to increase in the cases of coexpression
      of electron-donating partners of CYP17A1. The highest specific activity value
      (1.30 +/- 0.02 min-1) was achieved for the strain Y. lipolytica DC5, expressing
      CYP17A1 and the yeast's NADPH-cytochrome P450 reductase. The dye was also
      metabolized by pure CYP17A1 into the N-dealkylated derivatives, and gave a type I
      difference spectrum when titrated into low-spin CYP17A1. Analogously, docking
      simulations demonstrated that 25-NBD-cholesterol binds into the active site of
      the microbial cholesterol oxidase (CHOX) from Brevibacterium sterolicum (binding
      energy value of -5.6 kcal.mol-1). The steroid was found to be converted into its
      4-en-3-one derivative by CHOX (K(m) and k(cat) values were estimated to be 58.1
      +/- 5.9 MUM and 0.66 +/- 0.14 s-1, respectively). The 4-en-3-one derivative was
      also detected as the product of 25-NBD-cholesterol oxidation with both pure
      microbial cholesterol dehydrogenase (CHDH) and a pathogenic bacterium,
      Pseudomonas aeruginosa, possessing CHOXs and CHDHs. These results provide novel
      opportunities for investigation of the structure-function relationships of the
      aforementioned oxidoreductases, which catalyze essential steps of steroid
      bioconversion in mammals (CYP17A1) and bacteria (CHOX and CHDH), with
      fluorescence-based techniques.

PMID- 23551930
TI  - Standardization of pre-analytical variables in plasma microparticle
      determination: results of the International Society on Thrombosis and Haemostasis
      SSC Collaborative workshop.
AB  - Microparticles (MP) are sub-micron sized vesicles released by activated or
      apoptotic cells. They are generally defined as 0.1 to 1 MUm membrane particles
      that expose the anionic phospholipid phosphatidylserine (PS) and membrane
      antigens representative of their cellular origin [1]. It is now well recognized
      that MP behave as vectors of bioactive molecules, playing a role in blood
      coagulation, inflammation, cell activation and cancer metastasis. In clinical
      practice, circulating MP originating from blood and vascular cells are elevated
      in a variety of prothrombotic and inflammatory disorders, cardiovascular
      diseases, autoimmune conditions, infectious diseases and cancer [1-3]. (c) 2013
      International Society on Thrombosis and Haemostasis.

PMID- 23551931
TI  - Heme deficiency of soluble guanylate cyclase induces gastroparesis.
AB  - BACKGROUND: Soluble guanylate cyclase (sGC) is the principal target of nitric
      oxide (NO) to control gastrointestinal motility. The consequence on nitrergic
      signaling and gut motility of inducing a heme-free status of sGC, as induced by
      oxidative stress, was investigated. METHODS: sGCbeta1 (H105F) knock-in (apo-sGC)
      mice, which express heme-free sGC that has basal activity, but cannot be
      stimulated by NO, were generated. KEY RESULTS: Diethylenetriamine NONOate did not
      increase sGC activity in gastrointestinal tissue of apo-sGC mice. Exogenous NO
      did not induce relaxation in fundic, jejunal and colonic strips, and pyloric
      rings of apo-sGC mice. The stomach was enlarged in apo-sGC mice with hypertrophy
      of the muscularis externa of the fundus and pylorus. In addition, gastric
      emptying and intestinal transit were delayed and whole-gut transit time was
      increased in the apo-sGC mice, while distal colonic transit time was maintained.
      The nitrergic relaxant responses to electrical field stimulation at 1-4 Hz were
      abolished in fundic and jejunal strips from apo-sGC mice, but in pyloric rings
      and colonic strips, only the response at 1 Hz was abolished, indicating the
      contribution of other transmitters than NO. CONCLUSIONS & INFERENCES: The results
      indicate that the gastrointestinal consequences of switching from a native sGC to
      a heme-free sGC, which cannot be stimulated by NO, are most pronounced at the
      level of the stomach establishing a pivotal role of the activation of sGC by NO
      in normal gastric functioning. In addition, delayed intestinal transit was
      observed, indicating that nitrergic activation of sGC also plays a role in the
      lower gastrointestinal tract.

PMID- 23551932
TI  - Trajectories of PTSD risk and resilience in World Trade Center responders: an 8
      year prospective cohort study.
AB  - BACKGROUND: Longitudinal symptoms of post-traumatic stress disorder (PTSD) are
      often characterized by heterogeneous trajectories, which may have unique pre-,
      peri- and post-trauma risk and protective factors. To date, however, no study has
      evaluated the nature and determinants of predominant trajectories of PTSD
      symptoms in World Trade Center (WTC) responders. METHOD: A total of 10835 WTC
      responders, including 4035 professional police responders and 6800 non
      traditional responders (e.g. construction workers) who participated in the WTC
      Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the
      WTC attacks. RESULTS: Among police responders, longitudinal PTSD symptoms were
      best characterized by four classes, with the majority (77.8%) in a
      resistant/resilient trajectory and the remainder exhibiting chronic (5.3%),
      recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non
      traditional responders, a six-class solution was optimal, with fewer responders
      in a resistant/resilient trajectory (58.0%) and the remainder exhibiting
      recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%),
      delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric
      history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical
      conditions were most strongly associated with symptomatic trajectories of PTSD
      symptoms in both groups of responders, whereas greater education and family and
      work support while working at the WTC site were protective against several of
      these trajectories. CONCLUSIONS: Trajectories of PTSD symptoms in WTC responders
      are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk
      and protective factors. Police responders were more likely than non-traditional
      responders to exhibit a resistant/resilient trajectory. These results underscore
      the importance of prevention, screening and treatment efforts that target high
      risk disaster responders, particularly those with prior psychiatric history, high
      levels of trauma exposure and work-related medical morbidities.

PMID- 23551933
TI  - Safety and tolerability of a 2009 trivalent inactivated split-virion influenza
      vaccine in infants, children and adolescents.
AB  - OBJECTIVE: To evaluate the safety of CSL's split-virion inactivated trivalent
      2009 Southern Hemisphere formulation influenza vaccine (TIV) in children.
      METHODS: We enrolled 1992 healthy children into three groups: Cohorts A, >= 6
      months to <3 years; B, >= 3 years to <9 years; and C, >= 9 years to <18 years.
      Children received one or two doses of 0.25 ml (22.5 MUg haemagglutinin) or 0.5 ml
      (45 MUg) TIV, depending on age and prior vaccination history. We collected post
      vaccination solicited adverse event (AE) data (days 0-6), including fever
      (temperature: >= 37.5 degrees C axilla, >= 38.0 degrees C oral), unsolicited AEs
      (days 0-29) and serious AEs (SAEs) and new-onset chronic illnesses (NOCIs; to day
      180 after last vaccination). RESULTS: At least one solicited AE was reported by
      80%/78%/78% of children in Cohorts A, B and C, respectively. Systemic AEs were
      more common among Cohort A (72% of participants), and local AEs were more common
      among Cohort C (71% of participants). Fever was more common in younger cohorts,
      in influenza vaccine-naive children (29% of Cohort A receiving their first dose),
      and following first compared with second doses. Severe fever following a first
      dose prevented 20 participants receiving their second scheduled vaccine dose. A 7
      month-old participant had a single uncomplicated febrile convulsion on the day of
      vaccination. CONCLUSIONS: Nearly 80% of subjects reported at least one solicited
      AE following immunization. Fever prevalence was highest in vaccine-naive Cohort A
      participants, similar to other paediatric studies using CSL vaccine. Further
      research to understand fever-related AEs in children following CSL's TIV is
      recommended.

PMID- 23551934
TI  - The STBUR questionnaire for predicting perioperative respiratory adverse events
      in children at risk for sleep-disordered breathing.
AB  - BACKGROUND: In the absence of formal polysomnography (PSG), many children with
      symptoms of sleep-disordered breathing (SDB) go unrecognized and thus may be at
      risk for perioperative respiratory adverse events (PRAE). OBJECTIVES: To develop
      a simple practical tool to identify children with symptoms consistent with SDB
      who may be at risk for PRAE. METHODS: Three-hundred and thirty-seven parents of
      children scheduled for surgery completed the Sleep-Related Breathing Disorder
      (SRBD) questionnaire. Data regarding the incidence and severity of PRAE including
      airway obstruction and laryngospasm, were collected prospectively. RESULTS:
      Thirty-two (9.5%) children had a confirmed diagnosis of SDB by PSG and 90 (26.7%)
      had symptoms consistent with SDB based on the SRBD questionnaire. Principal
      component analysis identified five symptoms from the SRBD questionnaire that were
      strongly predictive of PRAE and which were incorporated into the STBUR tool
      (Snoring, Trouble Breathing, Un-Refreshed). The likelihood of PRAE was increased
      by threefold (positive likelihood ratio 3.06 [1.64-5.96] in the presence of any 3
      STBUR symptoms and by tenfold when all five symptoms were present (9.74 [1.35
      201.8]). In comparison, the likelihood of PRAE based on a PSG-confirmed diagnosis
      of SDB was 2.63 (1.17-6.23). CONCLUSIONS: Children presenting for surgery with
      symptoms consistent with SDB may be at risk for PRAE. It is important therefore
      that anesthesia providers identify these individuals prior to surgery to avoid
      potential complications. The STBUR questionnaire appears promising as a simple,
      clinically useful tool for identifying children at risk for PRAE. Further studies
      to validate the STBUR questionnaire as a diagnostic tool may be warranted.

PMID- 23551935
TI  - Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized,
      double-blind, placebo-controlled trial.
AB  - AIM: Hepatic edema is manifested by ascites, lower limb edema and intolerable
      symptoms. Some patients insufficiently respond to the conventional diuretic
      therapy. Therefore, a novel therapeutic option is required. We conducted a phase
      3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated
      with liver cirrhosis. METHODS: In our multicenter, randomized, double-blind,
      placebo-controlled trial, liver cirrhosis patients who showed insufficient
      response to conventional diuretics were randomly assigned to 7-day administration
      of either tolvaptan at 7.5 mg/day or placebo as an add-on therapy to conventional
      diuretics. The primary outcome was change in bodyweight from baseline. RESULTS:
      Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change
      in bodyweight from baseline on the final dosing day was -0.44 kg (standard
      deviation [SD], 1.93) in the placebo group and -1.95 kg (SD, 1.77) in the
      tolvaptan group (P < 0.0001). Improvement rates for lower limb edema and ascites
      related clinical symptoms were higher with tolvaptan than with placebo. Even in
      patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater
      with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan
      significantly increased serum sodium concentration from baseline. CONCLUSION: Add
      on therapy with tolvaptan was effective for the treatment of hepatic edema and
      ascites-related clinical symptoms. Furthermore, tolvaptan is expected to improve
      low serum sodium concentration and to exert its effect regardless of serum
      albumin level. Add-on therapy with tolvaptan is therefore considered to be a
      novel therapeutic option for hepatic edema.

PMID- 23551936
TI  - TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene
      expression, and cell proliferation of fission yeast.
AB  - Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging
      from yeast to humans. Fission yeast is emerging as a popular model organism to
      study TOR signaling, although rapamycin has been thought to not affect cell
      growth in this organism. Here, we analyzed the effects of rapamycin and caffeine,
      singly and combined, on multiple cellular processes in fission yeast. The two
      drugs led to diverse and specific phenotypes that depended on TORC1 inhibition,
      including prolonged chronological lifespan, inhibition of global translation,
      inhibition of cell growth and division, and reprograming of global gene
      expression mimicking nitrogen starvation. Rapamycin and caffeine differentially
      affected these various TORC1-dependent processes. Combined drug treatment
      augmented most phenotypes and effectively blocked cell growth. Rapamycin showed a
      much more subtle effect on global translation than did caffeine, while both drugs
      were effective in prolonging chronological lifespan. Rapamycin and caffeine did
      not affect the lifespan via the pH of the growth media. Rapamycin prolonged the
      lifespan of nongrowing cells only when applied during the growth phase but not
      when applied after cells had stopped proliferation. The doses of rapamycin and
      caffeine strongly correlated with growth inhibition and with lifespan extension.
      This comprehensive analysis will inform future studies into TORC1 function and
      cellular aging in fission yeast and beyond. 

PMID- 23551937
TI  - Electroacupuncture improves thermal and mechanical sensitivities in a rat model
      of postherpetic neuralgia.
AB  - BACKGROUND: Electroacupuncture (EA) is effective in relieving pain in patients
      with postherpetic neuralgia (PHN). However, the mechanism underlying the
      therapeutic effect of EA in PHN is still unclear. Systemic injection of
      resiniferatoxin (RTX), an ultrapotent analog of TRPV1 agonist, in adult rats can
      reproduce the clinical symptoms of PHN by ablating TRPV1-expressing sensory
      neurons. In this study, we determined the beneficial effect of EA and the
      potential mechanisms in this rat model of PHN. METHODS: PHN was induced in rats
      by a single injection of RTX. Thermal hyperalgesia was tested with a radiant heat
      stimulus, and mechanical allodynia was quantified with von Frey filaments. TRPV1
      receptors were shown by using immunofluorescence labeling. The ultrastructural
      changes of the sciatic nerve were assessed by electron microscopic examination.
      The sprouting of myelinated primary afferent terminals into the spinal dorsal
      horn was mapped by using the transganglionic tracer cholera toxin B-subunit
      (CTB). RESULTS: RTX injection diminished thermal sensitivity and gradually
      induced tactile allodynia within 3 weeks. EA applied to GB30 and GB34 at 2 and 15
      Hz, but not 100 Hz, significantly increased the thermal sensitivity 4 weeks after
      treatment and decreased the tactile allodynia 2 weeks after treatment in RTX
      treated rats. EA treatment at 2 and 15 Hz recovered the loss of TRPV1-positive
      dorsal root ganglion neurons and their central terminals of afferent fibers in
      the spinal superficial dorsal horn of RTX-treated rats. Moreover, EA
      significantly reduced the loss of unmyelinated fibers and the damage of the
      myelinated nerve fibers of RTX-treated rats. Furthermore, EA at 2 and 15 Hz
      inhibited the sprouting of myelinated primary afferent terminals into the spinal
      lamina II of RTX-treated rats. CONCLUSIONS: EA treatment improves thermal
      perception by recovering TRPV1-positive sensory neurons and nerve terminals
      damaged by RTX. EA Also reduces RTX-induced tactile allodynia by attenuating the
      damage of myelinated afferent nerves and their abnormal sprouting into the spinal
      lamina II. Our study provides new information about the mechanisms of the
      therapeutic actions of EA in the treatment of PHN.

PMID- 23551938
TI  - Emerging infectious diseases and public health policy: insights from Cambodia,
      Hong Kong and Indonesia.
AB  - Emerging infectious diseases affect the health of animal and human populations,
      but the impact goes beyond health as it extends to political, economic, social
      and environmental domains, as well as inter-state relations. Deeper understanding
      of these impacts aids public health authorities in their duties of protection and
      improvement of the health of their communities, promotion of healthy practices
      and research on disease, injury and threat prevention and mitigation. This
      empirical essay gathers insights from Cambodia, Hong Kong and Indonesia as they
      attempt to design and implement control and surveillance systems against avian
      influenza - an infectious disease. 

PMID- 23551939
TI  - The impact of chemotherapy-associated neutrophil/ lymphocyte counts on prognosis
      of adjuvant chemotherapy in colorectal cancer.
AB  - BACKGROUND: Leukocytes play an important role in cancer development. However, the
      impact of chemotherapy-associated neutropenia/lymphopenia on the prognosis of
      adjuvant chemotherapy is unknown. Here, we aimed to explore the impact of
      chemotherapy-associated neutrophil/lymphocyte counts on prognosis of adjuvant
      chemotherapy in colorectal cancer (CRC) and the risk factors for developing
      neutropenia/lymphopenia which showed impact on the prognosis of CRC receiving
      adjuvant chemotherapy. METHODS: From February 2003 to January 2011, 243 stage II
      and III CRC patients receiving adjuvant chemotherapy were enrolled in this
      retrospective study. The associations between neutrophil/ lymphocyte counts and
      disease free survival (DFS)/overall survival (OS) of CRC, and the risk factors
      for neutropenia/lymphopenia were investigated. RESULTS: No association of
      chemotherapy-associated neutrophil counts and CRC recurrence (AUC = 0.474, P =
      0.534), death (AUC = 0.449, P = 0.249) was found by ROC analysis. However, the
      chemotherapy-associated lymphocyte counts could significantly affect CRC
      recurrence (AUC = 0.634, P = 0.001), or death(AUC = 0.607, P = 0.015), with a
      optimized cut-off of 0.66 * 10(9)/L for recurrence, and 0.91 * 10(9)/L for death,
      respectively. Kaplan-Meier method showed chemotherapy-associated lymphopenia
      <0.66 * 10(9)/L was associated with shorter DFS (P < 0.0001), and chemotherapy
      associated lymphopenia <0.91 * 10(9)/L was associated with shorter OS (P =
      0.003). Cox regression model showed chemotherapy-associated lymphopenia <0.66 *
      10(9)/L was the independent prognostic factor for DFS (HR, 3.521; 95%CI = 1.703
      7.282), and chemotherapy-associated lymphopenia <0.91 * 10(9)/L was the
      independent prognostic factor for OS (HR, 2.083; 95% CI = 1.103-3.936).
      Multivariate logistic regression showed the risk of developing chemotherapy
      associated lymphopenia <0.66 * 10(9)/L was found in those with pretreatment CEA
      >=10 ng ml(-1) (OR, 3.338; 95% CI = 1.523-7.315), and the risk of developing
      chemotherapy-associated lymphopenia <0.91 * 10(9)/L was found in those with age
      >60 years (OR, 2.872; 95% CI = 1.344-6.136). CONCLUSIONS: Chemotherapy-associated
      lymphopenia <0.66 * 10(9)/L /0.91 * 10(9)/L has a significant impact on the
      prognosis of CRC receiving adjuvant chemotherapy. Pretreatment CEA >=10 ng ml(-1)
      is the independent risk factor for developing lymphopenia <0.66 * 109/L, and age
      >60 years is the independent risk factor for developing lymphopenia <0.91 *
      10(9)/L during adjuvant chemotherapy of CRC.

PMID- 23551940
TI  - Inequity in child health: the importance of early childhood development.

PMID- 23551941
TI  - Glycosaminoglycans in infectious disease.
AB  - Glycosaminoglycans (GAGs) are complex carbohydrates that are ubiquitously present
      on the cell surface and in the extracellular matrix. Interactions between GAGs
      and pathogens represent the first line of contact between pathogen and host cell
      and are crucial to a pathogen's invasive potential. Their complexity and
      structural diversity allow GAGs to control a wide array of biological
      interactions influencing many physiological and pathological processes, including
      adhesion, cell-to-cell communication, biochemical cascades, and the immune
      response. In recent years, increasing evidence indicates an extraordinary role
      for GAGs in the pathogenesis of viruses, bacteria and parasites. Herein, we
      examine the interface between GAGs and different pathogens, and address the
      divergent biological functions of GAGs in infectious disease. We consider
      approaches to use this understanding to design novel therapeutic strategies
      addressing new challenges in the treatment of infectious diseases. 

PMID- 23551942
TI  - Does the Cyanophora paradoxa genome revise our view on the evolution of
      photorespiratory enzymes?
AB  - In the present-day O2 -rich atmosphere, the photorespiratory pathway is essential
      for organisms performing oxygenic photosynthesis; i.e. cyanobacteria, algae and
      land plants. The presence of enzymes for the plant-like 2-phosphoglycolate cycle
      in cyanobacteria indicates that, together with oxygenic photosynthesis, genes for
      photorespiratory enzymes were endosymbiotically conveyed from ancient
      cyanobacteria to photosynthetic eukaryotes. The genome information for Cyanophora
      paradoxa, a member of the Glaucophyta representing the first branching group of
      primary endosymbionts, and for many other eukaryotic algae was used to shed light
      on the evolutionary relationship of photorespiratory enzymes among oxygenic
      phototrophs. For example, it became possible to analyse the phylogenies of 2
      phosphoglycolate phosphatase, serine:glyoxylate aminotransferase and
      hydroxypyruvate reductase. Analysis of the Cyanophora genome provided clear
      evidence that some photorespiratory enzymes originally acquired from
      cyanobacteria were lost, e.g. glycerate 3-kinase, while others were replaced by
      the corresponding enzymes from the alpha-proteobacterial endosymbiont, e.g.
      serine:glyoxylate aminotransferase. Generally, our analysis supports the view
      that many C2 cycle enzymes in eukaryotic phototrophs were obtained from the
      cyanobacterial endosymbiont, but during the subsequent evolution of algae and
      land plants multiple losses and replacements occurred, which resulted in a
      reticulate provenance of photorespiratory enzymes with different origins in
      different cellular compartments.

PMID- 23551943
TI  - Impact of radiofrequency ablation for patients with varicose veins on the budget
      of the German statutory health insurance system.
AB  - OBJECTIVES: In contrast to other countries, surgery still represents the common
      invasive treatment for varicose veins in Germany. However, radiofrequency
      ablation, e.g. ClosureFast, becomes more and more popular in other countries due
      to potential better results and reduced side effects. This treatment option may
      cause less follow-up costs and is a more convenient procedure for patients, which
      could justify an introduction in the statutory benefits catalogue. Therefore, we
      aim at calculating the budget impact of a general reimbursement of ClosureFast in
      Germany. METHODS: To assess the budget impact of including ClosureFast in the
      German statutory benefits catalogue, we developed a multi-cohort Markov model and
      compared the costs of a "World with ClosureFast" with a "World without
      ClosureFast" over a time horizon of five years. To address the uncertainty of
      input parameters, we conducted three different types of sensitivity analysis (one
      way, scenario, probabilistic). RESULTS: In the Base Case scenario, the
      introduction of the ClosureFast system for the treatment of varicose veins saves
      costs of about 19.1 Mio. ? over a time horizon of five years in Germany. However,
      the results scatter in the sensitivity analyses due to limited evidence of some
      key input parameters. CONCLUSIONS: Results of the budget impact analysis indicate
      that a general reimbursement of ClosureFast has the potential to be cost-saving
      in the German Statutory Health Insurance.

PMID- 23551944
TI  - Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human
      skeletal muscle protein metabolism.
AB  - Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium
      (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino
      acid leucine (Leu) possesses the most marked anabolic characteristics in acting
      as a trigger element for the initiation of protein synthesis. While the
      mechanisms by which Leu is 'sensed' have been the subject of great scrutiny, as a
      branched-chain amino acid, Leu can be catabolized within muscle, thus posing the
      possibility that metabolites of Leu could be involved in mediating the anabolic
      effect(s) of Leu. Our objective was to measure muscle protein anabolism in
      response to Leu and its metabolite HMB. Using [1,2-(13)C2]Leu and
      [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or
      Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also
      measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed
      3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid
      bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated
      muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both
      increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was
      more pronounced with Leu (i.e. p70S6K1 signalling 90 min vs. 30 min for HMB). HMB
      consumption also attenuated muscle protein breakdown (MPB; -57%) in an insulin
      independent manner. We conclude that exogenous HMB induces acute muscle anabolism
      (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional
      mechanism(s) to Leu.

PMID- 23551945
TI  - Parvalbumin tunes spike-timing and efferent short-term plasticity in striatal
      fast spiking interneurons.
AB  - Striatal fast spiking interneurons (FSIs) modulate output of the striatum by
      synchronizing medium-sized spiny neurons (MSNs). Recent studies have broadened
      our understanding of FSIs, showing that they are implicated in severe motor
      disorders such as parkinsonism, dystonia and Tourette syndrome. FSIs are the only
      striatal neurons to express the calcium-binding protein parvalbumin (PV). This
      selective expression of PV raises questions about the functional role of this
      Ca(2+) buffer in controlling FSI Ca(2+) dynamics and, consequently, FSI spiking
      mode and neurotransmission. To study the functional involvement of FSIs in
      striatal microcircuit activity and the role of PV in FSI function, we performed
      perforated patch recordings on enhanced green fluorescent protein-expressing FSIs
      in brain slices from control and PV-/- mice. Our results revealed that PV-/- FSIs
      fired more regularly and were more excitable than control FSIs by a mechanism in
      which Ca(2+) buffering is linked to spiking activity as a result of the
      activation of small conductance Ca(2+)-dependent K(+) channels. A modelling
      approach of striatal FSIs supports our experimental results. Furthermore, PV
      deletion modified frequency-specific short-term plasticity at inhibitory FSI to
      MSN synapses. Our results therefore reinforce the hypothesis that in FSIs, PV is
      crucial for fine-tuning of the temporal responses of the FSI network and for the
      orchestration of MSN populations. This, in turn, may play a direct role in the
      generation and pathology-related worsening of motor rhythms.

PMID- 23551946
TI  - Removal of half the sympathetic innervation does not reduce vasoconstrictor
      responses in rat tail artery.
AB  - Following reinnervation of denervated rat tail arteries, nerve-evoked
      contractions are at least as large as those evoked in normally innervated
      arteries despite a much lower nerve terminal density. Here nerve-evoked
      contractions have been investigated after transection of half the sympathetic
      innervation of normal tail arteries. After 1 week, the noradrenergic plexus 50-70
      mm along the tail was about half as dense as control. Excitatory junction
      potentials recorded in smooth muscle cells of arterial segments isolated in vitro
      were half their normal amplitude. Surprisingly, nerve-evoked contractions of
      isometrically mounted segments were not reduced in amplitude, as was also the
      case after only 3 days. After 1 week, enhancement of nerve-evoked contractions by
      blocking either neuronal re-uptake of noradrenaline with desmethylimipramine or
      prejunctional alpha2-adrenoceptors with idazoxan was similar to control,
      suggesting that these mechanisms are matched to the number of innervating axons.
      The relative contribution of postjunctional alpha2-adrenoceptors to contractions
      evoked by long trains of stimuli was enhanced but that of alpha1-adrenoceptors
      was unchanged. Transiently, sensitivity to the alpha1-adrenoceptor agonist
      phenylephrine was slightly increased. After 7 weeks, amplitudes of nerve-evoked
      contractions remained similar to control, and sensitivity to phenylephrine had
      recovered but that to the alpha2-adrenoceptor agonist clonidine was slightly
      raised. The normal amplitude of nerve-evoked contractions after partial
      denervation is only partly explained by the greater contribution of alpha2
      adrenoceptors. While the post-receptor mechanisms activated by nerve-released
      transmitter may be modified to amplify the contractions after partial
      denervation, our findings suggest that these mechanisms are normally saturated,
      at least in this artery.

PMID- 23551947
TI  - Quantifying the origins of population variability in cardiac electrical activity
      through sensitivity analysis of the electrocardiogram.
AB  - Altered function of ion channels in the heart can increase the risk of sudden
      arrhythmic death. Hundreds of genetic variants exist in these cardiac ion channel
      genes. The challenge is how to interpret the effects of multiple conductance
      perturbations on the complex multi-variable cardiac electrical system? In theory,
      sensitivity analysis can address this question. However, to date this approach
      has been restricted by computational overheads to analysis of isolated cells,
      which has limited extrapolation to physiologically relevant scales. The goal of
      this study was to extend existing sensitivity analyses to electrocardiogram (ECG)
      signals derived from multicellular systems and quantify the contribution of ionic
      conductances to emergent properties of the ECG. To achieve this, we have
      developed a highly parallelised simulation environment using unconventional high
      performance computing architectures to analyse the emergent electrical properties
      of a multicellular system. This has permitted the first systematic analysis of
      the molecular basis of the T wave amplitude, revealing important but distinct
      roles for delayed rectifier and inward rectifier K(+) currents. In addition to
      quantifying how interactions between multiple ion channels influence ECG
      parameters we show that these sensitivities are dynamic functions of heart rate.
      This study provides a significant advance in our understanding both of how
      individual ion conductances define ECG signals and of epistatic modification of
      cardiac electrical phenotypes. The parallelised simulation environment we have
      developed removes the computational roadblock that has limited this approach and
      so provides the framework for future analysis of more complex tissue and whole
      organ systems.

PMID- 23551949
TI  - Reinstatement in a cocaine versus food choice situation: reversal of preference
      between drug and non-drug rewards.
AB  - Recent studies show that when given a mutually exclusive choice between cocaine
      and food, rats almost exclusively choose food. The present experiment
      investigated potential shifts in preference between levers associated with either
      food or cocaine that might occur during extinction (food and cocaine no longer
      available) and during footshock-induced, cocaine-primed and food-primed
      reinstatement. During self-administration sessions where food and cocaine were
      simultaneously available, rats demonstrated a stable food preference, choosing
      food over cocaine on 83% of trials. During extinction when neither reinforcer was
      available, no preference between levers was evident and responding decreased
      until rats responded on the previously food- and cocaine-associated levers at
      equally low rates. Footshock resulted in a non-specific reinstatement of
      responding upon both levers, while cocaine priming resulted in a significant
      preference for cocaine seeking over food seeking. This suggests that the
      mechanism underlying footshock-induced reinstatement is distinct from that of
      cocaine-primed reinstatement. Food priming engendered a mild, non-specific
      increase in responding on both levers. Although rats generally prefer food over
      cocaine when presented with a choice between these primary reinforcers, the
      present results suggest that in certain situations, cocaine-seeking behavior
      prevails over food-seeking behavior. 

PMID- 23551948
TI  - Striatal neurones have a specific ability to respond to phasic dopamine release.
AB  - The cAMP/protein kinase A (PKA) signalling cascade is ubiquitous, and each step
      in this cascade involves enzymes that are expressed in multiple isoforms. We
      investigated the effects of this diversity on the integration of the pathway in
      the target cell by comparing prefrontal cortical neurones with striatal neurones
      which express a very specific set of signalling proteins. The prefrontal cortex
      and striatum both receive dopaminergic inputs and we analysed the dynamics of the
      cAMP/PKA signal triggered by dopamine D1 receptors in these two brain structures.
      Biosensor imaging in mouse brain slice preparations showed profound differences
      in the D1 response between pyramidal cortical neurones and striatal medium spiny
      neurones: the cAMP/PKA response was much stronger, faster and longer lasting in
      striatal neurones than in pyramidal cortical neurones. We identified three
      molecular determinants underlying these differences: different activities of
      phosphodiesterases, particularly those of type 4, which strongly damp the cAMP
      signal in the cortex but not in the striatum; stronger adenylyl cyclase activity
      in the striatum, generating responses with a faster onset than in the cortex; and
      DARPP-32, a phosphatase inhibitor which prolongs PKA action in the striatum.
      Striatal neurones were also highly responsive in terms of gene expression since a
      single sub-second dopamine stimulation is sufficient to trigger c-Fos expression
      in the striatum, but not in the cortex. Our data show how specific molecular
      elements of the cAMP/PKA signalling cascade selectively enable the principal
      striatal neurones to respond to brief dopamine stimuli, a critical process in
      incentive learning.

PMID- 23551950
TI  - Comparison of effects of tacrolimus ointment and mometasone furoate cream on the
      epidermal barrier of patients with atopic dermatitis.
AB  - BACKGROUND: The skin barrier plays a crucial role in the pathophysiology of
      atopic dermatitis. The quality of the skin barrier can be assessed using a new
      semi-quantitative method to measure intercellular lipid lamellae. This procedure
      was used to evaluate the influence of the topical application of the calcineurin
      inhibitor tacrolimus 0.1% ointment (Protopic(r)) versus mometasone furoate cream
      (Ecural(r)) on the quality of the skin barrier. PATIENTS AND METHODS: 20 adult
      patients with active atopic dermatitis (SCORAD 10-63) were included in an open,
      non-interventional study. Lesions on their forearms were treated twice daily over
      10 days with either tacrolimus 0.1% ointment or mometasone furoate cream. At the
      beginning and the end of the treatment period, SCORAD, TEWL and skin hydration
      were determined and the intercellular lipids were measured using transmission
      electron microscopy. RESULTS: The SCORAD improved in both groups nearly to the
      same extent, whereas TEWL and skin hydration improved significantly only in the
      tacrolimus group. Using the semi-quantitative analysis of intercellular lipid
      length per 1,000 nm(2) intercellular space, a twofold increase for mometasone
      furoate cream and a fourfold increase for tacrolimus 0.1% ointment were
      determined. CONCLUSIONS: In addition to its known antiinflammatory effect,
      tacrolimus 0.1% ointment leads also to a measurable increase of the lipids of the
      skin barrier in patients with atopic dermatitis, exceeding the effect of
      mometasone furoate cream.

PMID- 23551951
TI  - Bone loss in the oestrogen-depleted rat is not exacerbated by sitagliptin, either
      alone or in combination with a thiazolidinedione.
AB  - Antihyperglycaemic therapy on bone was evaluated in the ovariectomized (OVX), non
      diabetic adult rat. Animals were treated daily for 12 weeks with various doses of
      sitagliptin, pioglitazone, rosiglitazone, combinations of sitagliptin with
      pioglitazone or vehicle alone. Sitagliptin target engagement was confirmed by
      assessing inhibition of plasma dipeptidyl peptidase-4 (DPP-4) and oral glucose
      tolerance. Parameters related to bone health were evaluated in femur and
      vertebrae by dual-energy X-ray absorptiometry and histomorphometry. Bone mineral
      density (BMD) generally did not differ significantly between OVX-sitagliptin
      treated animals and OVX-vehicle controls. In lumbar vertebrae, however, there was
      significantly less BMD loss with increasing sitagliptin dose. Thiazolidinedione
      (TZD) treatment generally resulted in lower BMD; OVX-TZD-treated (but not OVX
      sitagliptin-treated) animals also had lessened cortical thickness in central
      femur and profoundly greater bone marrow adiposity in lumbar vertebrae. These
      findings support prior findings with TZDs and suggest a neutral or beneficial
      impact of DPP-4 inhibition on bone health. 

PMID- 23551953
TI  - Case report: Helicobacter suis infection in a pig veterinarian.
AB  - This study describes a non-Helicobacter (H.) pylori Helicobacter (NHPH) infection
      in a pig veterinarian. The patient suffered from reflux esophagitis and general
      dyspeptic symptoms and was referred to the hospital for upper gastrointestinal
      endoscopy. Histologic examination of corpus and antrum biopsies revealed a
      chronic gastritis. Large spiral-shaped non-H. pylori helicobacters could be
      visualized and were identified as H. suis by PCR. The patient was treated with a
      triple therapy, consisting of amoxicillin, clarithromycin, and pantoprazole for
      10 days. Successful eradication was confirmed after a follow-up gastrointestinal
      endoscopy and PCR 10 weeks after treatment. A mild chronic gastritis was,
      however, still observed at this point in time. This case report associates
      porcine H. suis strains with gastric disease in humans, thus emphasizing the
      zoonotic importance of H. suis bacteria from pigs.

PMID- 23551952
TI  - n-3 and n-6 Fatty acids are independently associated with lipoprotein-associated
      phospholipase A2 in the Multi-Ethnic Study of Atherosclerosis.
AB  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor
      for CVD and has been proposed as a marker of vascular inflammation.
      Polyunsaturated n-3 fatty acids (FA) and several n-6 FA are known to suppress
      inflammation and may influence Lp-PLA2 mass and activity. The associations of n-3
      and n-6 plasma FA with Lp-PLA2 mass and activity were analysed using linear
      regression analysis in 2246 participants of the Multi-Ethnic Study of
      Atherosclerosis; statistical adjustments were made to control for body mass,
      inflammation, lipids, diabetes, and additional clinical and demographic factors.
      Lp-PLA2 mass and activity were significantly lower in participants with the
      higher n-3 FA EPA (beta = - 4.72, P< 0.001; beta = - 1.53; P= 0.023) and DHA
      levels (beta = - 4.47, beta = - 1.87; both P< 0.001). Those in the highest
      quintiles of plasma EPA and DHA showed 12.71 and 19.15 ng/ml lower Lp-PLA2 mass
      and 5.7 and 8.90 nmol/min per ml lower Lp-PLA2 activity than those in the first
      quintiles, respectively. In addition, lower Lp-PLA2 mass and activity were
      associated with higher levels of n-6 arachidonic acid (beta = - 1.63, beta = -
      1.30; both P< 0.001), while gamma-linolenic acid was negatively associated with
      activity (beta = - 27.7, P= 0.027). Lp-PLA2 mass was significantly higher in
      participants with greater plasma levels of n-6 linoleic (beta = 0.828, P= 0.011)
      and dihomo-gamma-linolenic acids (beta = 4.17, P= 0.002). Based on their
      independent associations with Lp-PLA2 mass and activity, certain n-3 and n-6 FA
      may have additional influences on CVD risk. Intervention studies are warranted to
      assess whether these macronutrients may directly influence Lp-PLA2 expression or
      activity.

PMID- 23551954
TI  - Maximum dislodging forces of mandibular implant-assisted removable partial
      dentures: in vitro assessment.
AB  - PURPOSE: The initial retention of implant-assisted removable partial dentures
      (IARPDs) is unknown. The purpose of this in vitro study was to compare maximum
      dislodging forces of distal extension mandibular IARPD with two different
      attachments and three clasp designs. MATERIALS AND METHODS: A simulated class I
      partially edentulous mandible was prepared with two screw-type 3.75 * 12 mm
      implants in the first molar regions and 2 metal-ceramic crowns on distal
      abutments. Fifteen bilateral distal extension frameworks were conventionally
      fabricated in three clasp designs (suprabulge, infrabulge, no clasp). Locator
      attachments were connected to the 15 denture bases with autopolymerized resin.
      Each specimen was subject to four types of retention pulls (main, anterior,
      posterior, unilateral pull) five times with a universal testing machine. Locator
      attachments were replaced with O-ring attachments, and the same procedure was
      performed. Therefore, the study groups included: IRPD with Locator attachment and
      suprabulge clasp (group 1), IRPD with Locator attachment and infrabulge clasp
      (group 2), IRPD with Locator attachment and no clasp (group 3), IRPD with O-ring
      attachment and suprabulge clasp (group 4), IRPD with O-ring attachment and
      infrabulge clasp (group 5), IRPD with O-ring attachment and no clasp (group 6).
      Data were analyzed using one-way ANOVA, two-way ANOVA, and Tukey tests. RESULTS:
      The highest mean value was 22.99 lb for prostheses with a Locator attachment and
      suprabulge clasp. The lowest retentive values were recorded for IARPDs with O
      ring attachments. CONCLUSION: The results of this in vitro study suggest that the
      precise selection of attachments with or without clasp assemblies may affect the
      clinical success of mandibular IARPDs.

PMID- 23551955
TI  - Labor induction by transcervical balloon catheter and cerebral palsy associated
      with umbilical cord prolapse.
AB  - AIM: The aim of this study was to determine whether the use of transcervical
      balloon catheter (TCBC) for induction of labor (IOL) is a risk factor for
      cerebral palsy (CP) associated with umbilical cord prolapse (UCP-CP) in singleton
      pregnancies with cephalic presentation. MATERIAL AND METHODS: Among all 102
      infants with CP who were preliminarily determined as caused by antenatal and/or
      intrapartum hypoxemia by the Japan Council for Quality Health Care until April
      2012, all 56 infants who met all of the following criteria were studied: cephalic
      singleton pregnancy, reassuring fetal status on electronic cardiotocogram at time
      of admission to obstetric facilities for labor pains, ruptured fetal membranes,
      and/or IOL, and hypoxic-ischemic encephalopathy at birth. Clinical backgrounds
      were compared between six infants with UCP-CP and the remaining 50 infants with
      CP not associated with UCP (non-UCP-CP). RESULTS: Frequencies of IOL (83% [5/6]
      vs 32% [16/50], P = 0.0236), use of TCBC (67% [4/6] vs 10% [5/50], P = 0.0044),
      and amniotomy (67% [4/6] vs 24% [12/50], P = 0.0494) were significantly higher in
      the UCP-CP than the non-UCP-CP group. Only TCBC was a risk factor significantly
      associated with UCP-CP after logistic regression analysis, yielding an odds ratio
      of 18.0 (95% confidence interval, 2.6-124; P = 0.003). Saline volumes of 80-150
      mL were used for TCBC inflation in the four UCP-CP patients. CONCLUSION: Use of
      TCBC with a saline volume >= 80 mL was a significant risk factor for UCP-CP;
      however, the absolute risk of UCP-CP was estimated to be very low, approximately
      one in 7875 TCBC users.

PMID- 23551956
TI  - Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese
      patients with Parkinson's disease: a randomized, double-blind, parallel
      controlled, multi-centre trial.
AB  - Rasagiline mesylate is a highly potent, selective and irreversible monoamine
      oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to
      levodopa for patients with Parkinson's disease (PD). However, few studies have
      evaluated the efficacy and safety of rasagiline in the Chinese population. This
      study was designed to investigate the safety and efficacy of rasagiline as
      adjunctive therapy to levodopa treatment in Chinese PD patients. This was a
      randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial
      conducted over a 12-wk period that enrolled 244 PD patients with motor
      fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1
      mg) or placebo, once daily. Altogether, 219 patients completed the trial.
      Rasagiline showed significantly greater efficacy compared with placebo. During
      the treatment period, the primary efficacy variable--mean adjusted total daily
      off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d
      rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's
      Disease Rating Scale also improved during rasagiline treatment. Rasagiline was
      well tolerated. This study demonstrated that rasagiline mesylate is effective and
      well tolerated as an adjunct to levodopa treatment in Chinese PD patients with
      fluctuations.

PMID- 23551957
TI  - Regulatory T cells get nervous in the melanoma microenvironment.

PMID- 23551958
TI  - Choosing nursing as a career: a narrative analysis of Millennial nurses' career
      choice of virtue.
AB  - The growth and sustainability of the nursing profession depends on the ability to
      recruit and retain the upcoming generation of professionals. Understanding the
      career choice experiences and professional expectations of Millennial nurses
      (born 1980 or after) is a critical component of recruitment and retention
      strategies. This study utilized Polkinghorne's interpretive, narrative approach
      to understand how Millennial nurses explain, account for and make sense of their
      choice of nursing as a career. The positioning of nursing as a virtuous choice
      was both temporally and contextually influenced. The decision to enter the
      profession was initially emplotted around a traditional understanding of nursing
      as a virtuous profession: altruistic, noble, caring and compassionate. The
      centricity of virtues depicts one-dimensional understanding of the nursing
      profession that alone could prove dissatisfying to a generation of professionals
      who have many career choices available to them. The narratives reveal how
      participants' perceptions and expectations remain influenced by a stereotypical
      understanding of nursing, an image that remains prevalent in society and which
      holds implications for the future recruitment, socialization and retention
      strategies for upcoming and future generations of nurses. 

PMID- 23551959
TI  - Breast cancer survival of Hispanic women in the USA is influenced by country of
      origin.
AB  - AIM: People of Hispanic origin comprise nearly 16 percent of the (US) population.
      With the growing population of Hispanics in the USA, an important epidemiological
      question is whether their country of origin affects survival in Hispanic women
      living in the USA at the time of diagnosis of breast cancer. METHODS: We searched
      the Surveillance Epidemiology and End Results (SEER) database for Hispanic women
      with a single primary breast cancer with known country of origin diagnosed
      between 1973 and 2008. Univariate and multivariate analyses were performed to
      evaluate whether the country of origin was an independent predictor of survival.
      RESULTS: In total, 48,849 female breast cancer patients of Hispanic origin were
      included in the SEER database. Nearly 23 percent of them had an origin in Mexico,
      9 percent in South or Central America 3 percent in Puerto Rico, 2 percent in
      Cuba, 0.3 percent in the Dominical Republic and 3 percent in other countries,
      including Europe. About 60 percent of patients were identified as Hispanic by
      their surname or classified as Spanish/Hispanic not otherwise specified. Median
      survival of patients in these groups was 204, 240, 142, 169, 82.4, 115.5 and 210
      months, respectively (P < 0.0001 by log-rank test). Univariate and multivariate
      analysis showed that the country of origin was an independent predictor of
      survival in Hispanic women with breast cancer. CONCLUSION: The country of origin
      is an independent predictor of overall survival among Hispanic women diagnosed
      with breast cancer.

PMID- 23551960
TI  - Application and machine accuracy of a new frameless computed tomography-guided
      stereotactic brain biopsy system in dogs.
AB  - The purpose of this study was to describe application and machine accuracy for a
      new computed tomography (CT) guided, frameless, stereotactic brain biopsy system
      in dogs. Heads from ten canine cadavers were secured to a bite-plate with six
      attached fiducial markers and imaged using CT. Fiducialized CT images were
      imported into stereotactic software and spherical phantom lesions between 3.9 and
      5.5 mm in diameter were created in six locations. Infrared cameras and reflective
      markers were used to register fiducials to the reconstructed image set.
      Coordinates in the X, Y, and Z planes were identified for each lesion center.
      Iohexol (1.5 MUl of 240 mgI/ml) was injected into the center of each lesion and
      CT scans were repeated. Pre- and postinjection CT images for each cadaver were
      fused using the system software. Application accuracy was calculated using the
      center of each phantom lesion and the center of each injected contrast material
      location. Machine accuracy was calculated using a phantom with known distances
      between four fixed points in the X, Y, and Z planes. Mean application accuracy in
      the first 5 cadavers was 4.3 mm (95% confidence interval [CI] 2.9-4.3 mm) and in
      the second 5 cadavers was 2.9 mm (95% CI 2-3.9 mm). The more superficial lesions
      were targeted significantly less accurately than the deeper lesions (P = 0.0183).
      Median machine accuracy was 0.1 mm and the range was 0.1-0.2 mm. Findings
      supported use of the new biopsy system for canine brain lesions >3.9 mm in
      diameter. 

PMID- 23551961
TI  - FcgammaRIIa proteolysis as a diagnostic biomarker for heparin-induced
      thrombocytopenia.
AB  - BACKGROUND: A significant challenge in the management of heparin-induced
      thrombocytopenia (HIT) patients is making a timely and accurate diagnosis. The
      readily available enzyme immunoassays (EIAs) have low specificities. In contrast,
      platelet activation assays have higher specificities, but they are technically
      demanding and not widely available. In addition, ~ 10% of samples referred for
      HIT testing are initially classified as indeterminate by the serotonin release
      assay (SRA), which further delays accurate diagnosis. HIT is characterized by
      platelet activation, which leads to FcgammaRIIa proteolysis. This raises the
      possibility that identification of the proteolytic fragment of FcgammaRIIa could
      serve as a surrogate marker for HIT. OBJECTIVES: To determine the specificity of
      platelet FcgammaRIIa proteolysis induced by sera from patients with HIT, and to
      correlate the results with those of the SRA. METHODS/PATIENTS: Sera from HIT
      patients and control patients with other thrombocytopenic/prothrombotic disorders
      were tested for their ability to proteolyse FcgammaRIIa. The results were
      correlated with anti-platelet factor 4 (PF4)/heparin antibodies (EIA), and
      heparin-dependent platelet activation (SRA). RESULTS: Only HIT patient samples
      (20/20) caused heparin-dependent FcgammaRIIa proteolysis, similar to what was
      shown by the SRA. None of the samples from the other patient groups or hospital
      controls caused FcgammaRIIa proteolysis. Among nine additional samples that
      tested indeterminate in the SRA, FcgammaRIIa proteolysis resolved five samples
      that had a positive anti-PF4/heparin EIA result; three had no FcgammaRIIa
      proteolysis, and two were shown to have heparin-dependent FcgammaRIIa proteolysis
      CONCLUSIONS: This study suggests that heparin-dependent FcgammaRIIa proteolysis
      is at least as specific as the SRA for the diagnosis of HIT.

PMID- 23551964
TI  - A cross-cultural comparison study of depression assessments conducted in Japan.
AB  - BACKGROUND: The advent of global clinical trials has necessitated the use of
      English-based rating instruments in diverse cultures where English is clearly not
      the primary language. The cross-cultural applicability of rating instruments
      developed in one language with only one cultural group is an important issue in
      both research and clinical settings where these instruments might be used. We
      examined the cross-cultural applicability of the Montgomery-Asberg Depression
      Rating Scale (MADRS) in Japan. METHODS: As part of a rater-training program for a
      clinical trial in Japan, we assessed inter-rater agreement using two videotaped
      MADRS interviews administered in Japanese and produced with English subtitles. We
      looked for possible interpretational variance that might have been generated by
      cultural differences between Japanese raters in Japan and English-speaking raters
      in the USA scoring the same interviews. RESULTS: The US and Japanese raters
      demonstrated high inter-rater agreement and no significant scoring difference on
      the total MADRS score. The subtitles in English did not adversely affect the
      overall scoring.We separately analyzed the 10 individual items from each of the
      two MADRS interviews used for rater training. Of the 20 items, 18 were concordant
      between the US and Japanese raters. In one interview, the US raters scored
      lassitude significantly higher (p = 0.013) and the inability to feel
      significantly lower (p = 0.037) than the Japanese raters, reflecting a possible
      interpretational difference on these items. CONCLUSION: Although developed in
      Europe, these findings support the general applicability of the MADRS to assess
      the severity of depressive symptoms in Japan. We did note significant scoring
      differences on 2 of the 20 individual items, suggesting a possible cultural
      difference. It is possible that more interviews might have revealed more
      interpretational differences. These findings highlight the need for cultural
      familiarity when assessing psychiatric patients.

PMID- 23551962
TI  - Modifying muscular dystrophy through transforming growth factor-beta.
AB  - Muscular dystrophy arises from ongoing muscle degeneration and insufficient
      regeneration. This imbalance leads to loss of muscle, with replacement by scar or
      fibrotic tissue, resulting in muscle weakness and, eventually, loss of muscle
      function. Human muscular dystrophy is characterized by a wide range of disease
      severity, even when the same genetic mutation is present. This variability
      implies that other factors, both genetic and environmental, modify the disease
      outcome. There has been an ongoing effort to define the genetic and molecular
      bases that influence muscular dystrophy onset and progression. Modifier genes for
      muscle disease have been identified through both candidate gene approaches and
      genome-wide surveys. Multiple lines of experimental evidence have now converged
      on the transforming growth factor-beta (TGF-beta) pathway as a modifier for
      muscular dystrophy. TGF-beta signaling is upregulated in dystrophic muscle as a
      result of a destabilized plasma membrane and/or an altered extracellular matrix.
      Given the important biological role of the TGF-beta pathway, and its role beyond
      muscle homeostasis, we review modifier genes that alter the TGF-beta pathway and
      approaches to modulate TGF-beta activity to ameliorate muscle disease. 

PMID- 23551963
TI  - Cytotoxic T lymphocyte antigen-4 +49A/G polymorphism does not affect
      susceptibility to autoimmune hepatitis.
AB  - BACKGROUND & AIMS: Single nucleotide polymorphisms (SNP) in the Cytotoxic T
      lymphocyte antigen-4 gene (CTLA-4) have been associated with several autoimmune
      diseases including autoimmune Hepatitis (AIH). In this chronic idiopathic
      inflammatory liver disease, conflicting results have been reported on the
      association with a SNP at position +49 in the CTLA-4 gene in small patient
      cohorts. Here, we established the role of this SNP in a sufficiently large cohort
      of AIH patients. METHODS: The study population consisted of 672 AIH patients
      derived from academic and regional hospitals in the Netherlands and was compared
      with 500 controls selected from the 'Genome of the Netherlands' project cohort.
      Genotype frequencies were assessed by PCR for patients and by whole genome
      sequencing for controls. RESULTS: No significant differences in allele
      frequencies were found between patients and controls (G Allele: 40% vs 39%, P =
      0.7). Similarly, no significant differences in genotype frequencies between
      patients and controls were found. Finally, there was no relation between disease
      activity and the G allele or AG and GG genotypes. CONCLUSION: The Cytotoxic T
      Lymphocyte Antigen-4 +49 A/G polymorphism does not represent a major
      susceptibility risk allele for AIH in Caucasians and is not associated with
      disease severity at presentation.

PMID- 23551965
TI  - Eradication of hepatitis C virus could improve immunological status and pyoderma
      gangrenosum-like lesions.
AB  - Hepatitis C virus (HCV) can affect immune cells and induce various kinds of
      immune-related diseases including pyoderma gangrenosum. We experienced a
      difficult-to-treat case of pyoderma gangrenosum-like lesions in a patient with
      HCV infection. The patient was treated with pegylated interferon (PEG IFN)-alpha
      2b and ribavirin (RBV) therapy and achieved a sustained virological response.
      Before the eradication of HCV, the frequency of T-helper 17 cells was remarkably
      high in comparison to chronic hepatitis C patients without extrahepatic immune
      related diseases. Moreover, we could detect negative and positive strand-specific
      HCV RNA in the CD19(+) B lymphocytes and CD4(+) T lymphocytes. However, after the
      eradication of HCV, the immunological status became normal and the pyoderma
      gangrenosum-like lesions became stable without immunosuppressive therapy. Here,
      we report a sequential immunological analysis during PEG IFN/RBV therapy and the
      beneficial effect of HCV eradication in difficult-to-treat pyoderma gangrenosum
      like lesions. 

PMID- 23551966
TI  - Chaperonin 60: a paradoxical, evolutionarily conserved protein family with
      multiple moonlighting functions.
AB  - Chaperonin 60 is the prototypic molecular chaperone, an essential protein in
      eukaryotes and prokaryotes, whose sequence conservation provides an excellent
      basis for phylogenetic analysis. Escherichia coli chaperonin 60 (GroEL), the
      prototype of this family of proteins, has an established oligomeric-structure
      based folding mechanism and a defined population of folding partners. However,
      there is a growing number of examples of chaperonin 60 proteins whose crystal
      structures and oligomeric composition are at variance with GroEL, suggesting that
      additional complexities in the protein-folding function of this protein should be
      expected. In addition, many organisms have multiple chaperonin 60 proteins, some
      of which have lost their protein-folding ability. It is emerging that this highly
      conserved protein has evolved a bewildering variety of additional biological
      functions - known as moonlighting functions - both within the cell and in the
      extracellular milieu. Indeed, in some organisms, it is these moonlighting
      functions that have been left after the loss of the protein-folding activity.
      This highlights the major paradox in the biology of chaperonin 60. This article
      reviews the relationship between the folding and non-folding (moonlighting)
      activities of the chaperonin 60 family and discusses current knowledge on their
      molecular evolution focusing on protein domains involved in the non-folding
      chaperonin functions in an attempt to understand the emerging biology of this
      evolutionarily ancient protein family. 

PMID- 23551968
TI  - Nutritional disturbance in acid-base balance and osteoporosis: a hypothesis that
      disregards the essential homeostatic role of the kidney.
AB  - The nutritional acid load hypothesis of osteoporosis is reviewed from its
      historical origin to most recent studies with particular attention to the
      essential but overlooked role of the kidney in acid-base homeostasis. This
      hypothesis posits that foods associated with an increased urinary acid excretion
      are deleterious for the skeleton, leading to osteoporosis and enhanced fragility
      fracture risk. Conversely, foods generating neutral or alkaline urine would
      favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic
      fracture risk. This theory currently influences nutrition research, dietary
      recommendations and the marketing of alkaline salt products or medications meant
      to optimise bone health and prevent osteoporosis. It stemmed from classic
      investigations in patients suffering from chronic kidney diseases (CKD) conducted
      in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a
      buffer system to acid accumulation. This interpretation was later questioned on
      both theoretical and experimental grounds. Notwithstanding this questionable role
      of bone mineral in systemic acid-base equilibrium, not only in CKD but even more
      in the absence of renal impairment, it is postulated that, in healthy
      individuals, foods, particularly those containing animal protein, would induce
      'latent' acidosis and result, in the long run, in osteoporosis.Thus, a
      questionable interpretation of data from patients with CKD and the subsequent
      extrapolation to healthy subjects converted a hypothesis into nutritional
      recommendations for the prevention of osteoporosis. In a historical perspective,
      the present review dissects out speculation from experimental facts and
      emphasises the essential role of the renal tubule in systemic acid-base and Ca
      homeostasis.

PMID- 23551967
TI  - A combined blood based gene expression and plasma protein abundance signature for
      diagnosis of epithelial ovarian cancer--a study of the OVCAD consortium.
AB  - BACKGROUND: The immune system is a key player in fighting cancer. Thus, we sought
      to identify a molecular 'immune response signature' indicating the presence of
      epithelial ovarian cancer (EOC) and to combine this with a serum protein
      biomarker panel to increase the specificity and sensitivity for earlier detection
      of EOC. METHODS: Comparing the expression of 32,000 genes in a leukocytes
      fraction from 44 EOC patients and 19 controls, three uncorrelated shrunken
      centroid models were selected, comprised of 7, 14, and 6 genes. A second
      selection step using RT-qPCR data and significance analysis of microarrays
      yielded 13 genes (AP2A1, B4GALT1, C1orf63, CCR2, CFP, DIS3, NEAT1, NOXA1, OSM,
      PAPOLG, PRIC285, ZNF419, and BC037918) which were finally used in 343 samples (90
      healthy, six cystadenoma, eight low malignant potential tumor, 19 FIGO I/II, and
      220 FIGO III/IV EOC patients). Using new 65 controls and 224 EOC patients
      (thereof 14 FIGO I/II) the abundances of six plasma proteins (MIF, prolactin,
      CA125, leptin, osteopondin, and IGF2) was determined and used in combination with
      the expression values from the 13 genes for diagnosis of EOC. RESULTS: Combined
      diagnostic models using either each five gene expression and plasma protein
      abundance values or 13 gene expression and six plasma protein abundance values
      can discriminate controls from patients with EOC with Receiver Operator
      Characteristics Area Under the Curve values of 0.998 and bootstrap .632+
      validated classification errors of 3.1% and 2.8%, respectively. The sensitivities
      were 97.8% and 95.6%, respectively, at a set specificity of 99.6%. CONCLUSIONS:
      The combination of gene expression and plasma protein based blood derived
      biomarkers in one diagnostic model increases the sensitivity and the specificity
      significantly. Such a diagnostic test may allow earlier diagnosis of epithelial
      ovarian cancer.

PMID- 23551969
TI  - Tembusu virus in human, China.
AB  - SUMMARY: Tembusu virus (TMUV) infection in ducks, geese and house sparrows was
      reported in China. To confirm the emergence of TMUV in humans, we investigated
      TMUV as a possible infection in duck industry workers in Shandong, China. Of 132
      serum samples tested, 95 (71.9%) had TMUV antibodies. In oral swabs detection, 63
      (47.7%) samples were positive for TMUV RNA. Nucleotide sequences of 277 bp coding
      the partial NS3 protein showed more than 99.5% identity with other duck TMUV
      strains, which can cause severe egg drop in ducks. These findings contribute to
      the realization that TMUV may be overlooked as a zoonotic transmission in China.

PMID- 23551970
TI  - Gore Bio-A((r)) fistula plug for complex anal fistula: the results should be
      interpreted cautiously.

PMID- 23551972
TI  - Plasma tau levels in Alzheimer's disease.

PMID- 23551971
TI  - Effects of traumatic brain injury on intestinal contractility.
AB  - BACKGROUND: Patients with traumatic brain injury (TBI) often suffer from
      gastrointestinal dysfunction including intolerance to enteral feedings. However,
      it is unclear how TBI affects small intestinal contractile activity. The purpose
      of this study was to determine if TBI affects intestinal smooth muscle function.
      METHODS: Sprague-Dawley rats were subjected to controlled cortical impact injury
      (TBI). Sham animals underwent a similar surgery but no injury (SHAM). Animals
      were sacrificed 1, 3, and 7 days after TBI and intestinal smooth muscle tissue
      was collected for measurement of contractile activity and transit, NF-kB
      activity, and cytokine levels. Brains were collected after sacrifice to determine
      volume loss due to injury. KEY RESULTS: Contractile activity decreased
      significantly in ileum, but not jejunum, in the TBI group 7 days after injury
      compared with SHAM. Brain volume loss increased significantly 7 days after injury
      compared with 3 days and correlated significantly with the contractile activity 1
      day after injury. In the intestinal smooth muscle, NF-kB activity increased
      significantly in the TBI group 3 and 7 days after injury vs SHAM. Wet to dry
      weight ratio, indicating edema, also increased significantly in the TBI group.
      Interleukin-1alpha, -1beta, and -17 increased significantly in the TBI group
      compared with SHAM. CONCLUSIONS & INFERENCES: Traumatic brain injury causes a
      delayed but significant decrease in intestinal contractile activity in the ileum
      leading to delayed transit. The decreased intestinal contractile activity is
      attributed to secondary inflammatory injury as evidenced by increased NF-kB
      activity, increased edema, and increased inflammatory cytokines in the intestinal
      smooth muscle.

PMID- 23551973
TI  - Progressive emergence of an oseltamivir-resistant A(H3N2) virus over two courses
      of oseltamivir treatment in an immunocompromised paediatric patient.
AB  - A minor viral population of oseltamivir-resistant A(H3N2) viruses (E119V
      neuraminidase mutation) was selected and maintained in a continually infected
      immunocompromised child following initial oseltamivir treatment. A subsequent
      course of oseltamivir given 7 weeks later rapidly selected for the E119V variant
      resulting in a near-pure population of the resistant virus. The study highlights
      the challenges of oseltamivir treatment of immunocompromised patients that are
      continually shedding virus and demonstrates the ability of the E119V oseltamivir
      resistant virus to be maintained for prolonged periods even in the absence of
      drug-selective pressure. 

PMID- 23551974
TI  - D-2-hydroxyglutarate metabolism is linked to photorespiration in the shm1-1
      mutant.
AB  - The Arabidopsis mutant shm1-1 is defective in mitochondrial serine
      hydroxymethyltransferase 1 activity and displays a lethal photorespiratory
      phenotype at ambient CO2 concentration but grows normally at high CO2 . After
      transferring high CO2 -grown shm1-1 plants to ambient CO2 , the younger leaves
      remain photosynthetically active while developed leaves display increased
      yellowing and decreased FV /FM values. Metabolite analysis of plants transferred
      from high CO2 to ambient air indicates a massive light-dependent
      (photorespiratory) accumulation of glycine, 2-oxoglutarate (2OG) and D-2
      hydroxyglutarate (D-2HG). Amino acid markers of senescence accumulated in ambient
      air in wild-type and shm1-1 plants maintained in darkness and also build up in
      shm1-1 in the light. This, together with an enhanced transcription of the
      senescence marker SAG12 in shm1-1, suggests the initiation of senescence in shm1
      1 under photorespiratory conditions. Mitochondrial D-2HG dehydrogenase (D-2HGDH)
      converts D-2HG into 2OG. In vitro studies indicate that 2OG exerts competitive
      inhibition on D-2HGDH with a Ki of 1.96 mm. 2OG is therefore a suitable candidate
      as inhibitor of the in vivo D-2HGDH activity, as 2OG is produced and accumulates
      in mitochondria. Inhibition of the D-2HGDH by 2OG is likely a mechanism by which
      D-2HG accumulates in shm1-1, however it cannot be ruled out that D-2HG may also
      accumulate due to an active senescence programme that is initiated in these
      plants after transfer to photorespiratory conditions. Thus, a novel interaction
      of the photorespiratory pathway with cellular processes involving D-2HG has been
      identified.

PMID- 23551975
TI  - Intelligence and psychopathy: a correlational study on insane female offenders.
AB  - BACKGROUND: The occurrence of a significant relationship between psychopathic
      traits and intelligence is still open to debate. Most of the relevant information
      has been obtained from crystallized IQ tests or on psychopathic male offenders.
      In this study we hypothesized a negative correlation between psychopathic traits
      and fluid intelligence on a sample of criminal female in-patients. METHOD: We
      carried out a correlational study on a selected sample of 56 criminal female
      offenders. Variables that were measured include the Hare Psychopathy Checklist
      Revised (PCL-R) total score (and, separately, the scores from its four subscales:
      Interpersonal, Affective, Lifestyle and Antisocial) and fluid IQ measured by
      Raven's Progressive Matrices (RPM). RESULTS: Pearson's correlation between RPM IQ
      and total PCL-R score was negative (r(54) = -0.55, p < 0.001); women with greater
      psychopathy traits (total PCL-R score) had lower IQ scores. Negative correlations
      were also found between IQ and the four PCL-R subscales, Interpersonal,
      Affective, Lifestyle and Antisocial (r(54) = -0.35, p < 0.01, r(54) = -0.52, p <
      0.001, r(54) = -0.53, p < 0.001, and r(54) = -0.49, p < 0.001 respectively).
      CONCLUSIONS: The results indicate a general negative relationship between PCL-R
      and IQ, equally distributed across the four subcomponents of the psychopathic
      trait, and support the view that unsuccessful psychopathic women have poor
      planning and are unable to foresee and represent future consequences of their
      actions.

PMID- 23551976
TI  - Meeting report from the Society for Melanoma Research 2012 Congress, Hollywood,
      California.

PMID- 23551977
TI  - C560Rbeta3 caused platelet integrin alphaII b beta3 to bind fibrinogen
      continuously, but resulted in a severe bleeding syndrome and increased murine
      mortality.
AB  - BACKGROUND AND OBJECTIVES: beta(3)-Deficient megakaryocytes were modified by
      human beta(3)-lentivirus transduction and transplantation to express sufficient
      levels of a C560Rbeta(3) amino acid substitution, for investigation of how an
      activated alphaII b beta(3) conformation affects platelets in vivo in mice.
      PATIENT/METHODS: As in our previous report of an R560beta(3) mutation in a
      patient with Glanzmann thrombasthenia, R560beta(3) murine platelets spontaneously
      bound antibody that only recognizes activated alphaII b beta3 bound to its
      ligand, fibrinogen. RESULTS: With this murine model, we showed that alphaII b 
      R560beta3 mutation-mediated continuous binding of fibrinogen occurred in the
      absence of P-selectin surface expression, indicating that the integrin was in an
      active conformation, although the platelets circulated in a quiescent manner.
      Remarkably, only 35% of R560beta(3) 'mutant' mice survived for 6 months after
      transplantation, whereas 87% of C560beta(3) 'wild-type' mice remained alive.
      Pathologic examination revealed that R560beta(3) mice had enlarged spleens with
      extramedullary hematopoiesis and increased hemosiderin, indicating hemorrhage.
      R560beta(3) megakaryocytes and platelets showed abnormal morphology and irregular
      granule distribution. Interestingly, R560beta(3) washed platelets could aggregate
      upon simultaneous addition of fibrinogen and physiologic agonists, but
      aggregation failed when platelets were exposed to fibrinogen before activation in
      vitro and in vivo. CONCLUSIONS: The results demonstrate that continuous occupancy
      of alphaIIb beta3 with fibrinogen disrupts platelet structure and function,
      leading to hemorrhagic death consistent with Glanzmann thrombasthenia rather than
      a thrombotic state.

PMID- 23551978
TI  - Comparison of the EORTC QLQ-BM22 and the BOMET-QOL quality of life questionnaires
      in patients with bone metastases.
AB  - AIMS: Bone metastases are a common complication of advanced cancer and often
      result in a decrease in patients' quality of life. Very few specific modules have
      been created to accurately assess quality of life in this patient group. The
      purpose of this study was to compare two questionnaires, the European
      Organization for Research and Treatment of Cancer quality of life questionnaire
      for patients with bone metastases (EORTC QLQ-BM22) and the bone metastases
      quality of life questionnaire (BOMET-QOL. METHODS: A literature search was
      conducted in Medline, Health and Psychosocial Instruments, Embase and Embase
      Classic to identify studies that discussed the development, validation and
      reliability of the (EORTC) QLQ-BM22 and the BOMET-QOL. Studies that discussed the
      development and validity of the questionnaire along with studies using these
      tools were included. RESULTS: Both questionnaires were developed in collaboration
      with patients and health-care professionals. The QLQ-BM22 is over twice the
      length of the BOMET-QOL, with 22 questions as compared to 10. The QLQ-BM22 has
      four subscales while the BOMET-QOL has no subscales. The QLQ-BM22 gives a more in
      depth analysis of symptoms and well-being and includes issues such as mobility,
      side effects, complications of treatment and dependency. The BOMET-QOL is shorter
      and gives an overall assessment of pain and mobility. Scoring, item format,
      organization and response options vary between the questionnaires but the recall
      period for both is the previous week. Both questionnaires have been determined
      valid and reliable. CONCLUSION: The QLQ-BM22 and the BOMET-QOL are designed
      specifically for patients with bone metastases and each has strengths and
      weaknesses. Use of one over the other is ultimately dependent on trial design and
      investigators' goals.

PMID- 23551979
TI  - Increased alcohol consumption in rats after subchronic antidepressant treatment.
AB  - The use of antidepressants for alcoholism in humans has been a matter of
      controversy in recent years. Despite the existence of an important co-morbidity
      for depression and alcoholism, some studies suggest that the use of
      antidepressants could worsen the prognosis of alcoholism. However, there is a
      lack of studies in animal models exploring this phenomenon. In the present study,
      we show how the 15-d treatment with fluoxetine (10 mg/kg) or venlafaxine (50
      mg/kg) affected alcohol deprivation effect (ADE) and subsequent alcohol
      consumption. Initially, fluoxetine reduced ADE and venlafaxine did not affect it.
      However, in the following days, both antidepressants increased alcohol
      consumption, an effect that was found to last at least 5 wk. Fluoxetine treatment
      was shown to cause a locomotor sensitized response to a challenge dose of
      amphetamine (0.5 mg/kg), indicating the presence of a supersensitive dopaminergic
      transmission. In summary, antidepressant treatment may increase alcohol
      consumption in rats after a period of alcohol deprivation and this could be
      related to alterations in the reward circuitry. This finding confirms in an
      animal model previous reports in humans that may limit the use of antidepressants
      for alcoholism. 

PMID- 23551980
TI  - A global view of transcriptome dynamics during flower development in chickpea by
      deep sequencing.
AB  - Measurement of gene expression can provide important clues about gene function
      and molecular basis of developmental processes. Here, we have analysed the
      chickpea transcriptome in vegetative and flower tissues by exploiting the
      potential of high-throughput sequencing to measure gene expression. We mapped
      more than 295 million reads to quantify the transcript abundance during flower
      development. We detected the expression of more than 90% genes in at least one
      tissue analysed. We found quite a large number of genes were differentially
      expressed during flower development as compared to vegetative tissues. Further,
      we identified several genes expressed in a stage-specific manner. Various
      transcription factor families and metabolic pathways involved in flower
      development were elucidated. The members of MADS-box family were most represented
      among the transcription factor genes up-regulated during various stages of flower
      development. The abundant expression of several well-known genes implicated in
      flower development in chickpea flower development stages confirmed our results.
      In addition, we detected the expression specificities of lineage-specific genes
      during flower development. The expression data presented in this study is the
      most comprehensive dataset available for chickpea as of now and will serve as
      resource for unraveling the functions of many specific genes involved in flower
      development in chickpea and other legumes. 

PMID- 23551981
TI  - Spin glass to superconducting phase transformation by oxidation of a molybdo
      cuprate: Mo0.3Cu0.7Sr2TmCu2Oy.
AB  - A detailed study of the structure and properties for the as-prepared and oxygen
      annealed Mo0.3Cu0.7Sr2TmCu2Oy material is reported. The Cu/Mo cationic
      distribution is established using a combination of x-ray/neutron powder
      diffraction refinement. The chemical substitution of the Mo ions for the Cu ions
      in the CuYSr2Cu2O(7-delta) structure is found to occur in both of the copper
      sites for the as-prepared sample. Interestingly, no trace of Mo substitution in
      the copper plane site is found to occur after oxygenation. The as-prepared
      Mo0.3Cu0.7Sr2TmCu2Oy material is found to be a spin glass (SG) system and
      explained on the basis of the cluster-by-cluster freezing model. On the other
      hand, the oxygen annealed material is superconducting (SC) (T(SC,onset) = 31 K).
      A peak has been observed in the critical current density plot and can be
      explained on the basis of field induced pins. The influence of oxygen annealing
      in the structure and properties of this material are presented and discussed.
      This seems to be the first case of a SG-SC transformation following an oxidation
      reaction in cuprates.

PMID- 23551982
TI  - Abstracts of the Third Annual Meeting of the Associazione Italiana Sistema
      Nervoso Periferico. April 18-20, 2013. Verona, Italy.

PMID- 23551984
TI  - Chemoembolization-induced arterial damage: Evaluation of three different
      chemotherapeutic protocols using epirubicin and miriplatin.
AB  - AIM: We aimed to evaluate hepatic vascular changes following lipiodol-based
      transarterial chemoembolization of hepatocellular carcinoma using epirubicin
      (EPI), miriplatin (MPT) and miriplatin plus low-dose epirubicin (MPT+EPI).
      METHODS: A total of 185 arteries in 118 patients who underwent chemoembolization
      using EPI (67 arteries in 48 patients), MPT (64 arteries in 37 patients) and
      MPT+EPI (54 arteries in 33 patients) were retrospectively examined. The maximum
      dose limit of MPT was 140 mg and that of EPI was 50 and 20 mg for the EPI and
      MPT+EPI groups, respectively. Vascular changes and local recurrence were
      evaluated by subsequent angiography. Factors affecting arterial damage were
      analyzed using multivariate logistic regression analysis. RESULTS: More severe
      arterial damage was observed in the EPI group (88.1%) than in the MPT+EPI (72.2%)
      and the MPT (18.7%) groups (P = 0.044 and P < 0.001, respectively). EPI usage
      (hazard ratio [HR] = 12.8, P < 0.001), selective chemoembolization (HR = 5.4, P <
      0.001) and MPT usage (HR = 0.28, P = 0.020) were significant predictors for
      arterial damage induction. The local recurrence rate was lower for the lesions
      exhibiting arterial occlusion after chemoembolization (39.4%) than for the
      lesions exhibiting no vascular attenuation (73.9%) or wall irregularity (75.8%)
      (P = 0.001 and P = 0.005, respectively). CONCLUSION: High-dose EPI, MPT, and low
      dose EPI plus MPT usage in chemoembolization for hepatocellular carcinoma induced
      the greatest, the least, and intermediate vascular damages, respectively.
      Therapeutic occlusion of tumor feeder vessels is associated with lower local
      recurrence.

PMID- 23551985
TI  - Medical management of paediatric burn injuries: best practice part 2.
AB  - Burns remain a leading cause of injury in the paediatric population in Australia
      despite efforts in prevention. Advances in surgical management include novel
      debridement methods and blood conserving techniques. Patients with severe burns
      (>20%) remain significantly more complex to manage as a result of extensive
      alterations in metabolic processes. There appears increasing evidence to support
      the use of pharmacological modulators of the hyper-metabolic state in these
      patients. The management of a child with burns involves acute, subacute and long
      term planning. This holistic approach seems optimally co-ordinated by a Burns
      Unit in which each discipline required to provide care to these children in order
      to achieve optimal outcomes is represented. 

PMID- 23551983
TI  - Enteral vs. intravenous ICU sedation management: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: A relevant innovation about sedation of long-term Intensive Care Unit
      (ICU) patients is the 'conscious target': patients should be awake even during
      the critical phases of illness. Enteral sedative administration is nowadays
      unusual, even though the gastrointestinal tract works soon after ICU admission.
      The enteral approach cannot produce deep sedation; however, it is as adequate as
      the intravenous one, if the target is to keep patients awake and adapted to the
      environment, and has fewer side effects and lower costs. METHODS/DESIGN: A
      randomized, controlled, multicenter, single-blind trial comparing enteral and
      intravenous sedative treatments has been done in 12 Italian ICUs. The main
      objective was to achieve and maintain the desired sedation level: observed RASS =
      target RASS +/- 1. Three hundred high-risk patients were planned to be randomly
      assigned to receive either intravenous propofol/midazolam or enteral
      melatonin/hydroxyzine/lorazepam. Group assignment occurred through online
      minimization process, in order to balance variables potentially influencing the
      outcomes (age, sex, SAPS II, type of admission, kidney failure, chronic
      obstructive pulmonary disease, sepsis) between groups. Once per shift, the staff
      recorded neurological monitoring using validated tools. Three flowcharts for
      pain, sedation, and delirium have been proposed; they have been designed to treat
      potentially correctable factors first, and, only once excluded, to administer
      neuroactive drugs. The study lasted from January 24 to December 31, 2012. A total
      of 348 patients have been randomized, through a centralized website, using a
      specific software expressly designed for this study. The created network of ICUs
      included a mix of both university and non-university hospitals, with different
      experience in managing enteral sedation. A dedicated free-access website was also
      created, in both Italian and English, for continuous education of ICU staff
      through CME courses. DISCUSSION: This 'educational research' project aims both to
      compare two sedative strategies and to highlight the need for a profound cultural
      change, improving outcomes by keeping critically-ill patients awake. TRIAL
      REGISTRATION NUMBER: Clinicaltrials.gov #NCT01360346.

PMID- 23551986
TI  - Prosthodontic and surgical management of a completely edentulous patient with a
      severe class III skeletal maxillomandibular relationship: a clinical report.
AB  - This article describes a multidisciplinary approach combining surgical and
      prosthodontic treatment of a completely edentulous patient who presented with a
      severe skeletal class III relationship and was diagnosed as American College of
      Prosthodontists Prosthodontic Diagnostic Index (ACP PDI) class IV. The use of a
      complete denture serving as diagnostic tool, surgical guide, and definitive
      restoration is presented. Computer-aided surgical simulation was used to achieve
      an accurate diagnostic and surgical plan. Maxillary Lefort class I and mandibular
      sagittal split osteotomy surgical treatment was performed to correct arch
      discrepancy. The surgical procedure demonstrated a clinically acceptable
      maxillomandibular relationship and stability. The patient was satisfied with the
      esthetics and demonstrated improved oral function following prosthesis insertion.

PMID- 23551988
TI  - Changes in the modulation of spinal pain processing are related to severity in
      irritable bowel syndrome.
AB  - BACKGROUND: In irritable bowel syndrome (IBS) patients can be divided in two
      groups according to inhibition or facilitation of the RIII nociceptive spinal
      reflex induced by rectal distension. We further investigated the differences in
      pain processes in these two groups and their relationship to clinical symptoms.
      METHODS: This study included 10 female IBS-C patients with facilitation (Group F)
      and 10 patients with inhibition (Group I) of the RIII reflex recorded on the left
      lower limb during slow-ramp rectal distension, and 11 healthy female volunteers.
      Diffuse noxious inhibitory control (DNIC)-induced inhibition was assessed by
      measuring the effects of noxious cold stimulation of the right hand on the RIII
      reflex and the concomitant sensation of pain. Functional magnetic resonance
      imaging (fMRI) was performed to compare the changes in brain activity induced by
      painful and non painful rectal distension. Irritable bowel syndrome symptom
      severity, mood, anxiety, and catastrophizing were also systematically assessed.
      KEY RESULTS: Unlike the patients of Group I and healthy volunteers, Group F
      patients displayed no inhibition of the RIII reflex or of concomitant pain
      sensation during immersion of the hand in ice-cold water. The reduction of the
      inhibition induced by heterotopic noxious stimuli was directly correlated with
      the severity of IBS symptoms, but not with psychological symptoms. The fMRI study
      showed that non-painful and painful rectal distension induced similar changes in
      brain activity in the two groups of patients. CONCLUSION & INFERENCES:
      Alterations of the modulation of spinal pain processing in IBS correlates with
      symptom severity but not with psychological factors or brain activity.

PMID- 23551987
TI  - The mdx mouse model as a surrogate for Duchenne muscular dystrophy.
AB  - Research into fundamental principles and the testing of therapeutic hypotheses
      for treatment of human disease is commonly performed on mouse models of human
      diseases. Although this is often the only practicable approach, it carries a
      number of caveats arising from differences between the two species. This review
      focuses on the example of skeletal muscle disease, in particular muscular
      dystrophy, to identify some of the principal classes of obstacles to translation
      of data from mouse to humans. Of these, the difference in scale is one of the
      most commonly ignored, and is of particular interest because it has quite major
      repercussions for evaluation of some classes of intervention and of outcome
      criteria, while having comparatively little bearing on others. Likewise, inter
      species differences and similarities in cell and molecular biological mechanisms
      underlying development, growth and response to pathological processes should be
      considered on an individual basis. An awareness of such distinctions is crucial
      if we are to avoid misjudging the likely applicability to humans of results
      obtained on mouse models. 

PMID- 23551989
TI  - The association between circulating oestradiol levels and severity of liver
      disease in males with hepatitis B virus infection.
AB  - BACKGROUND: Males have a strikingly increased risk of advanced liver disease.
      This study was designed to investigate the association between sex hormone levels
      and different disease states in hepatitis B virus (HBV)-infected male patients.
      METHODS: Two hundred and fifty-two male patients, including 30 with acute
      hepatitis B (AHB), 127 with chronic hepatitis B (CHB) and 95 with chronic severe
      hepatitis B (CSHB), and 48 healthy controls (HCs) were enroled in this study. All
      patients were followed for 4 months. The primary end point was in-hospital
      mortality at the end of 90 days. At study entry, a blood sample was collected
      from all subjects to examine liver function, renal function and sex hormone
      levels (serum total testosterone and oestradiol). A total of nine clinical
      chemistry and biochemical variables were analyzed for possible association with
      outcomes by using Cox proportional hazards and multiple regression models.
      RESULTS: We demonstrated that in CSHB and CHB patients, oestradiol levels were
      significantly increased compared with HCs and AHB patients, whereas no
      significant differences were observed in AHB patients and HCs. All male patients
      had normal levels of testosterone which were not significantly different compared
      with those of HCs. Increased oestradiol levels were clinically associated with
      severe liver disease, and increased 3-month mortality rate. Multivariate analysis
      demonstrated that oestradiol and the model for end-stage liver disease (MELD)
      score were independent predictors for mortality (both P < 0.001). CONCLUSION:
      Oestradiol levels are significantly increased in male patients with hepatitis B,
      and were associated with the severity of liver disease. Moreover, elevation of
      oestradiol is an independent predictive factor for the 3-month mortality rate in
      male patients with hepatitis B.

PMID- 23551990
TI  - Parallel evolution of senescence in annual fishes in response to extrinsic
      mortality.
AB  - BACKGROUND: Early evolutionary theories of aging predict that populations which
      experience low extrinsic mortality evolve a retarded onset of senescence.
      Experimental support for this theory in vertebrates is scarce, in part for the
      difficulty of quantifying extrinsic mortality and its condition- and density
      dependent components that -when considered- can lead to predictions markedly
      different to those of the "classical" theories. Here, we study annual fish of the
      genus Nothobranchius whose maximum lifespan is dictated by the duration of the
      water bodies they inhabit. Different populations of annual fish do not experience
      different strengths of extrinsic mortality throughout their life span, but are
      subject to differential timing (and predictability) of a sudden habitat
      cessation. In this respect, our study allows testing how aging evolves in natural
      environments when populations vary in the prospect of survival, but condition
      dependent survival has a limited effect. We use 10 Nothobranchius populations
      from seasonal pools that differ in their duration to test how this parameter
      affects longevity and aging in two independent clades of these annual fishes.
      RESULTS: We found that replicated populations from a dry region showed markedly
      shorter captive lifespan than populations from a humid region. Shorter lifespan
      correlated with accelerated accumulation of lipofuscin (an established age
      marker) in both clades. Analysis of wild individuals confirmed that fish from
      drier habitats accumulate lipofuscin faster also under natural conditions. This
      indicates faster physiological deterioration in shorter-lived populations.
      CONCLUSIONS: Our data provide a strong quantitative example of how extrinsic
      mortality can shape evolution of senescence in a vertebrate clade. Nothobranchius
      is emerging as a genomic model species. The characterization of pairs of closely
      related species with different longevities should provide a powerful paradigm for
      the identification of genetic variations responsible for evolution of senescence
      in natural populations.

PMID- 23551991
TI  - Development of sensitization to methamphetamine in offspring prenatally exposed
      to morphine, methadone and buprenorphine.
AB  - Heroin use among young women of reproductive age has drawn much attention around
      the world. However, there is lack of information on the long-term effects of
      prenatal exposure to opioids on their offspring. Our previous study demonstrated
      that prenatally buprenorphine-exposed offspring showed a marked change in the
      cross-tolerance to morphine compared with other groups. In the current study,
      this animal model was used to study effects of methamphetamine (METH)-induced
      behavioral sensitization in the offspring at their adulthood. The results showed
      no differences in either basal or acute METH-induced locomotor activity in any of
      the groups of animals tested. When male offspring received METH injections of 2
      mg/kg, i.p., once a day for 5 days, behavioral sensitization was induced, as
      determined by motor activity. Furthermore, the distance and rate of development
      (slope) of locomotor activity and conditioned place preference induced by METH
      were significantly increased in the prenatally buprenorphine-exposed animals
      compared with those in other groups. The dopamine D1 R in the nucleus accumbens
      of the prenatally buprenorphine-exposed offspring had lower mRNA expression; but
      no significant changes in the MU-, kappa-opioid, nociceptin, D2 R and D3 R
      receptors were noted. Furthermore, significant alterations were observed in the
      basal level of cAMP and the D1 R agonist enhanced adenylyl cyclase activity in
      the prenatally buprenorphine-exposed group. Overall, the study demonstrates that
      D1 R and its downregulated cAMP signals are involved in enhancing METH-induced
      behavioral sensitization in prenatally buprenorphine-exposed offspring. The study
      reveals that prenatal exposure to buprenorphine caused long-term effects on
      offspring and affected the dopaminergic system-related reward mechanism. 

PMID- 23551992
TI  - Improvement of the metabolic syndrome profile by soluble fibre - guar gum - in
      patients with type 2 diabetes: a randomised clinical trial.
AB  - A diet rich in fibre seems to protect against the metabolic syndrome (MetS), but
      there is scarce information about the role of fibre intake in patients with the
      MetS and diabetes. The aim of the present study was to evaluate the effects of
      soluble fibre from partially hydrolysed guar gum (PHGG) on the MetS and
      cardiovascular risk factors in patients with type 2 diabetes. In the present
      randomised controlled clinical trial, forty-four patients with type 2 diabetes
      (males 38.6 %, age 62 (SD 9) years, diabetes duration 14.2 (SD 9.6) years) and
      the MetS underwent clinical, laboratory and dietary evaluations at baseline, 4
      and 6 weeks. All patients followed their usual diet and the intervention group (n
      23) received an additional 10 g/d of PHGG. In the intervention group, waist
      circumference (WC), glycated Hb (HbA1c), 24 h urinary albumin excretion (UAE) and
      serum trans-fatty acids (FA) were reduced in comparison with baseline after 4 and
      6 weeks: WC 103.5 (SD 9.5) to 102.1 (SD 10) to 102.3 (SD 9.7) cm; HbA1c 6.88 (SD
      0.99) to 6.64 (SD 0.94) to 6.57 (SD 0.84) %; 24 h UAE 6.8 (interquartile range
      3.0-17.5) to 4.5 (interquartile range 3.0-10.5) to 6.2 (interquartile range 3.0
      9.5) mg; trans-FA 71 (interquartile range 46-137) to 67 (interquartile range 48
      98) to 57 (interquartile range 30-110) mg/l (P< 0.05 for all). The only change in
      the control group was weight reduction: 77.0 (SD 13.5) to 76.2 (SD 13.3) to 76.1
      (SD 13.4) kg (P= 0.005). Other MetS components (blood pressure, TAG, HDL
      cholesterol, fasting plasma glucose), total and LDL-cholesterol, C-reactive
      protein and endothelin-1 did not change in either group. In patients with type 2
      diabetes and the MetS, the addition of PHGG to the usual diet improved
      cardiovascular and metabolic profiles by reducing WC, HbA1c, UAE and trans-FA.

PMID- 23551993
TI  - Phase III studies on novel oral anticoagulants for stroke prevention in atrial
      fibrillation: a look beyond the excellent results: a reply to a rebuttal.

PMID- 23551994
TI  - Pathways through which health influences early retirement: a qualitative study.
AB  - BACKGROUND: Due to the aging of the population, there is a societal need for
      workers to prolong their working lives. In the Netherlands, many employees still
      leave the workforce before the official retirement age of 65. Previous
      quantitative research showed that poor self-perceived health is a risk factor of
      (non-disability) early retirement. However, little is known on how poor health
      may lead to early retirement, and why poor health leads to early retirement in
      some employees, but not in others. Therefore, the present qualitative study aims
      to identify in which ways health influences early retirement. METHODS: Face-to
      face semi-structured interviews were conducted with 30 employees (60-64 years)
      who retired before the official retirement age of 65. Participants were selected
      from the Study on Transitions in Employment, Ability and Motivation. The
      interviews were transcribed verbatim, a summary was made including a timeline,
      and the interviews were open coded. RESULTS: In 15 of the 30 persons, health
      played a role in early retirement. Both poor and good health influenced early
      retirement. For poor health, four pathways were identified. First, employees felt
      unable to work at all due to health problems. Second, health problems resulted in
      a self-perceived (future) decline in the ability to work, and employees chose to
      retire early. Third, employees with health problems were afraid of a further
      decline in health, and chose to retire early. Fourth, employees with poor health
      retired early because they felt pushed out by their employer, although they
      themselves did not experience a reduced work ability. A good health influenced
      early retirement, since persons wanted to enjoy life while their health still
      allowed to do so. The financial opportunity to retire sometimes triggered the
      influence of poor health on early retirement, and often triggered the influence
      of good health. Employees and employers barely discussed opportunities to prolong
      working life. CONCLUSIONS: Poor and good health influence early retirement via
      several different pathways. To prolong working life, a dialogue between employers
      and employees and tailored work-related interventions may be helpful.

PMID- 23551995
TI  - Ultra-protective tidal volume: how low should we go?
AB  - Applying tidal volumes of less than 6 mL/kg might improve lung protection in
      patients with acute respiratory distress syndrome. In a recent article, Retamal
      and colleagues showed that such a reduction is feasible with conventional
      mechanical ventilation and leads to less tidal recruitment and overdistension
      without causing carbon dioxide retention or auto-positive end-expiratory
      pressure. However, whether the compensatory increase in the respiratory rate
      blunts the lung protection remains unestablished. 

PMID- 23551996
TI  - Ligation of the intersphincteric fistula tract in the management of anal fistula.
      A systematic review.
AB  - AIM: Over the last 5 years, the ligation of the intersphincteric fistula tract
      (LIFT) procedure has become increasingly popular as a sphincter-preserving
      technique for the treatment of anal fistula. The aim of this article was to
      review the published literature on the LIFT procedure. METHOD: The Cochrane
      database and EMBASE were searched from January 1980 to November 2012, and PubMed
      from January 1966 to November 2012. All peer-reviewed studies that investigated
      the LIFT procedure for the treatment of anal fistula were eligible for inclusion.
      Technical notes, commentaries, letters and meeting abstracts were excluded. The
      primary outcome measured was the overall fistula closure rate in relation to the
      length of follow-up. RESULTS: Twenty-nine articles were originally identified
      using the search criteria. Thirteen were finally included for analysis. Sample
      sizes ranged from 18 to 93 patients, with a pooled total of 498. Most fistulae,
      494 (99%), were of cryptoglandular aetiology, of which 470 (94%) were
      transsphincteric. Overall success rates ranged from 40 to 95%, with a pooled
      success of 71% (352 of 495 patients; 3 of 498 were lost to follow-up). Follow-up
      ranged from 1 to 55 months, with a reported mean or median of 4 to 19.5 months.
      One hundred and eighty-three patients were formally assessed for continence, out
      of whom 11 (6%) had a minor disturbance. CONCLUSION: Overall the systematic
      review shows that the LIFT procedure appears to be an effective sphincter
      conserving approach for the treatment of transsphincteric anal fistula with a
      pooled healing rate of 71% over a mean or median follow-up period ranging from 4
      to 19.5 months.

PMID- 23551997
TI  - Primary wound closure with tension -- tips and tricks.

PMID- 23551998
TI  - A young woman with multiple cutaneous epithelioid angiomatous nodules (CEAN) on
      her forearm: a case report and follow-up of therapeutic intervention.
AB  - Cutaneous epithelioid angiomatous nodule (CEAN) is regarded as a very rare entity
      of benign vascular hyperplasia that clinically manifests as mainly single, small,
      rapidly-growing reddish to bluish nodules or papules, mainly on the head and neck
      of adults. Most patients present with solitary lesions. We present a 39-year-old
      female with multiple, rapidly-growing, erythematous nodules on her left forearm
      during a one-year period. The overall histologic picture suggested Cutaneous
      Epithelioid Angiomatous Nodule (CEAN). In this case we tried different treatments
      and compared the results.

PMID- 23551999
TI  - A case of lymphangioma circumscriptum successfully treated with
      electrodessication following failure of pulsed dye laser.
AB  - Lymphangioma circumscriptum is the most common cutaneous lymphatic malformation.
      It presents as a well-circumscribed, localized region of vesicles that can ooze
      and drain lymphatic and sanguineous fluid. The vesicles cause significant
      morbidity and psychological distress from itching, pain, drainage, and secondary
      infection. We report a case of a 16-year-old female with a life-long history of a
      weeping, hemorrhagic, and painful lesion on her right buttock causing significant
      emotional distress. We initially attempted therapeutic treatment with pulsed dye
      laser. The lesion appeared unchanged after two trials and we subsequently used
      three sessions of electrodessication to cauterize the aberrant vessels. The
      lesion largely resolved without complications and is no longer causing pain or
      emotional distress.

PMID- 23552000
TI  - Small primary cutaneous mucinous carcinoma mimicking an early basal cell
      carcinoma.
AB  - We report an early case of primary cutaneous mucinous carcinoma in a male patient
      with chronic actinic damage. Dermoscopic features influenced the clinical
      decision to obtain tissue for histopathology, which in turn revealed
      characteristic strands and nests amidst mucinous stroma. Immunohistochemistry did
      not confirm cutaneous origin of the tumor; instead a full internal malignancy
      screen was required. Clinicians should be aware of this rare entity, which most
      commonly occurs on the head and neck, and give advice on appropriate further
      investigations and management.

PMID- 23552001
TI  - Lupus miliaris disseminatus faciei: report of a new case and brief literature
      review.
AB  - Lupus miliaris disseminatus faciei (LMDF) is a rare dermatosis with
      characteristic clinicopathological features but of unknown etiolgy. We report a
      new typical case of LMDF. A 29-year-old man presented with an asymptomatic,
      micropapular midfacial eruption. Histological examination revealed a dermal
      granulomatous reaction with central areas of necrosis and occasionally
      degenerated hair follicles. Workup for sarcoidosis was negative. A moderate
      improvement was achieved with systemic treatment with doxycycline. A brief
      overview of the main features of LMDF is presented.

PMID- 23552002
TI  - Arborizing vessels under dermoscopy: a case of cellular neurothekeoma instead of
      basal cell carcinoma.
AB  - Neurothekeoma is a slow-growing, benign tumor of nerve sheath origin. Herein we
      present a 62-year-old female who presented with a 5-month history of a nodule
      that had shown a slight enlargement. She had a diagnosis of non-Hodgkin lymphoma
      for 10 years for which she had received multiple sessions of chemotherapy and
      radiotherapy. Cutaneous examination showed a well-defined, firm, 2 cm, pink-red
      nodule of the right supraclavicular area, which showed thick and arborizing
      vessels under dermoscopy. A diagnosis of cellular neurothekeoma was made after
      histopathologic examination with immunohistochemistry. Thick and arborizing
      vessels have been described as the dermoscopic hallmark of nodular and cystic
      basal cell carcinoma. In the past, hydradenoma and intraepidermal poroma have
      been defined as dermoscopic mimics of basal cell carcinoma because of the
      characteristic appearance of arborizing vessels. With this report a neurogenic
      tumor has been added to this list.

PMID- 23552003
TI  - Leg ulcer in Werner syndrome (adult progeria): a case report.
AB  - Werner syndrome (WS; MIM#277700) or adult progeria, is a rare disease, associated
      with mutations of a single gene (RECQL2 or WRN), located on chromosome 8 (8p12).
      It codes a DNA-helicase, whose defects cause genomic instability. The highest
      incidences are reported in Japan and Sardinia (Italy). On this major island of
      the Mediterranean Basin, the WS cases have been observed in the northern areas.
      The authors describe the apparently first case reported in southern Sardinia, a
      51-year-old woman, who was born in and resides in the province of Cagliari. She
      presented with a 9-year history of an intractable leg ulcer and other
      characteristic symptoms, including "bird-like" face, high-pitched voice,
      premature greying, short stature, abdominal obesity in contrast with thin body
      type, scleroderma-like legs, decreased muscle mass, diabetes, atherosclerosis,
      and premature menopause. A specialized genetic Institute of Research (IRCCS-IDI,
      Rome) confirmed the clinical diagnosis. There is no cure or specific treatment
      and patients must be periodically screened for an increased risk of
      cardiovascular and cerebrovascular disease and malignancies. Among the many
      findings, leg ulcers significantly affect the patient's quality of life. This
      problem may send the patient to the dermatologist, who finally suspects the
      diagnosis. Poor response to medical treatment may require aggressive repeated
      surgery, with poor or temporary results.

PMID- 23552004
TI  - Rocky Mountain Spotted Fever in a patient treated with anti-TNF-alpha inhibitors.
AB  - Rocky Mountain Spotted Fever (RMSF) is a tick-bourne illness, which can be fatal
      if unrecognized. We discuss the case of a patient treated with an anti-TNF-alpha
      inhibitor for rheumatoid arthritis who later developed a generalized erythematous
      macular eruption accompanied by fever. The clinical findings were suggestive of
      RMSF, which was later confirmed with serology. Prompt treatment with doxyclycine
      is recommended for all patients with clinical suspicion of RMSF.

PMID- 23552005
TI  - Unique presentations of epidermal growth factor receptor inhibitor-induced
      papulopustular eruption related to bacterial superinfection.
AB  - Epidermal growth factor receptor (EGFR) inhibitors have been reported to induce
      numerous cutaneous side effects, the most notable of which is a papulopustular
      eruption on the face, scalp, and central chest. The typical presentation consists
      of inflamed papules, often with pustules, favoring a seborrheic distribution. The
      pustules of the EGFR inhibitor-induced papulopustular eruption are commonly
      sterile but bacterial superinfection is not uncommon. We report two unique
      presentations of the papulopustular eruption that were found to be associated
      with Staphylococcus aureus superinfection. One patient presented with an abrupt
      onset of nearly confluent red plaques on the cheeks, forehead, chin, and neck,
      with innumerable studded pinpoint pustules. The other patient had a long-standing
      untreated papulopustular eruption on the scalp, which resulted in widespread
      erythema, large thick plaques of serous crust, pustular exudate, and associated
      alopecia. Both patients quickly resolved with non-tetracycline oral antibiotics
      combined with topical steroid treatment.

PMID- 23552006
TI  - Unknown: congenital linear whitish papules in a 3-year-old boy.

PMID- 23552007
TI  - Melanonychia induced by topical treatment of periungual warts with 5
      fluorouracil.
AB  - Periungal and subungual warts are benign epidermal neoplasms caused by human
      papillomaviruses. They represent a challenge for management because of resistance
      to treatment. 5-flourouracil is an antimetabolite that interferes with DNA
      synthesis and inhibits RNA formation. We present a 32-year-old female with
      subungual and periungual warts of the fingers of both hands and first right toe.
      She was treated with 5-fluorouracil twice daily under occlusion plus 20 percent
      urea. After a month she presented with grayish transverse melanonychia along and
      parallel to the lunula with some maceration of the periungal folds. Nail
      pigmentation may be a consequence of dermal deposition by systemic drugs and less
      frequently by topical drugs. In this case melanonychia was induced by the topical
      application of 5-fluorouracil. The brown-grayish pigmentation, with parallel
      involvement of the lunula of all the nails treated, presented like that induced
      by systemically administered cytotoxic drugs.

PMID- 23552008
TI  - Periocular keratotic nodule.

PMID- 23552009
TI  - Non-healing verrucous plaque over upper limb for 1 year in a tea garden worker.
AB  - A 55-year-old tea garden worker presented with a slowly growing verrucous plaque
      on the right arm. The diagnosis of chromomycosis was confirmed by the
      identification of brown sclerotic bodies in a skin biopsy.

PMID- 23552010
TI  - Acute angioedema response to topical 5-fluorouracil therapy.
AB  - This is a case report involving a patient who was treated with topical 5-FU cream
      and subsequently developed a severe case of angioedema. This case presents the
      possibility of anaphylaxis to topical 5-FU treatments and/or the interaction with
      angiotensin converting enzyme inhibitors. To our knowledge there has been no
      prior reported case of this reaction. We present this unusual case along with a
      review of the current literature on angioedema.

PMID- 23552011
TI  - The effectiveness of tap water iontophoresis for palmoplantar hyperhidrosis using
      a Monday, Wednesday, and Friday treatment regime.
AB  - Primary focal hyperhidrosis is a benign condition of unknown etiology. Tap water
      iontophoresis has long been known to inhibit sweat production. The mechanism of
      reduced hyperhidrosis by iontophoresis is not completely clear. For operational
      convenience, our patients received their treatments at different intervals to
      those recommended by the manufacturer of the iontophoresis unit. We performed a
      retrospective audit to evaluate the effectiveness of tap water iontophoresis
      using this regimen. This new treatment regimen was effective at controlling
      palmoplantar hyperhidrosis. Minimal undesirable effects such as mild skin
      irritation and erythema were noted but none were severe enough to necessitate
      discontinuation of treatment. In conclusion, tap water iontophoresis is a safe
      and effective treatment of palmar and plantar hyperhidrosis when used on Monday,
      Wednesday, and Friday for 4 weeks. Continued treatment is needed to maintain the
      effect and many patients go on to purchase their own machines. This technique
      should be considered prior to systemic or aggressive surgical intervention.

PMID- 23552012
TI  - Th-17 and the lack of efficacy of ustekinumab in pemphigus vulgaris.
AB  - Systemic corticosteroids represent an effective treatment for pemphigus vulgaris
      (PV). However, this treatment is related to many adverse side effects. Herein, we
      report a case of PV treated with ustekinumab.

PMID- 23552013
TI  - Acral erythema worsened by intravenous infusions of cyclosporin.
AB  - Acral erythema is a frequent cutaneous reaction related to chemotherapy. A
      patient presented herein developed acral erythema related to cytosine arabinoside
      treatment and then graft versus host disease (GVHD). Subsequently, worsening of
      palmar erythema and pain occurred with intravenous cyclosporin infusions.

PMID- 23552014
TI  - Role of human Toll-like receptors in naturally occurring influenza A infections.
AB  - BACKGROUND: We investigated the roles of Toll-like receptors (TLRs) in naturally
      occurring influenza. METHODS: A prospective, case - control study was conducted.
      Adults hospitalized with virologically confirmed influenza A infections (onset
      <48 hours, before treatment) were compared with age-/gender-matched controls.
      TLRs (2, 3, 4, 7, 8, 9) expression in monocytes and dendritic cells (DCs - total,
      myeloid, plasmacytoid) was quantitated using flow cytometry. Gene expression of
      RLRs (RIG-1, MDA-5) was evaluated using real-time PCR. Concomitant signaling
      molecules expression, plasma cytokine/chemokine concentrations, and respiratory
      tract viral loads were measured. PBMCs were cultured and stimulated ex vivo with
      TLR-specific ligands for cytokine responses. RESULTS: Forty two patients with
      influenza (24 A/H3N2, 18 A/H1N1pdm09) and 20 controls were studied. Patients'
      mean age was 68 +/- 16 years; 81% had respiratory/cardiovascular complications.
      There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during
      influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus
      strains. Higher TLR expression levels at presentation significantly correlated
      with lower viral loads (Spearman's rho: -0.46 to -0.69 for TLR9, TLR8, and TLR3;
      P-values <0.05). Multivariate regression models (adjusted for age, comorbidity,
      disease severity, time from onset) confirmed their independent associations.
      Increased signaling molecules (phospho-MAPKs, IkappaB) and inflammatory cytokines
      (IL-6, sTNFR-1, CCL2/MCP-1; CXCL10/IP-10, IFN-gamma) correlated with increased
      TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with
      influenza showed significant, dynamic changes in their cytokine responses upon
      TLR stimulation, compared with controls. CONCLUSIONS: Our results suggest that
      TLRs play an important role in early, innate viral inhibition in naturally
      occurring influenza. Inflammatory cytokine responses are concomitantly induced.
      These findings support investigation of TLR targeting as a novel intervention
      approach for prophylaxis against influenza.

PMID- 23552015
TI  - Relationship between fatigue and social support in hemodialysis patients.
AB  - The aim of this study was to evaluate the relationship between fatigue and social
      support in hemodialysis patients in Turkey. This study was conducted on 73
      patients receiving hemodialysis treatment in a hemodialysis unit in the province
      of Malatya between July and November 2011. A questionnaire consisting of 16
      questions for sociodemographic and disease data was used together with the
      Multidimensional Scale of Perceived Social Support (MSPSS) and the Fatigue
      Severity Scale (FSS). In statistical evaluation, the Mann-Whitney U-test,
      independent t-test, Kruskal-Wallis test, and Pearson's correlation analysis were
      used. Correlation analysis between severity of fatigue in hemodialysis patients
      and social support revealed a significant relationship in the negative direction
      between fatigue severity and support from family (r = -0.404, P < 0.05), support
      from friends (r = -0.635, P < 0.05), support from a special person (r = -0.638, P
      < 0.05) and overall support (r = -0.643, P < 0.05). Patients with severe fatigue
      had low mean scores for support from family, friends, a special person and
      overall, whereas a high level of social support decreased the level of fatigue.
      When giving care to patients on hemodialysis, nurses should consider the effect
      of social support on fatigue and approach their patients from this perspective. 

PMID- 23552016
TI  - National guidelines for high-cost drugs in Brazil: achievements and constraints
      of an innovative national evidence-based public health policy.
AB  - INTRODUCTION: The translation of best evidence into practice has become an
      important purpose of policy making in health care. In Brazil, a country of
      continental dimensions with widespread regional and social inequalities, the
      dissemination and use of the best-evidence in policy making is a critical issue
      for the healthcare system. OBJECTIVES: The main purpose of this study is to
      describe an evidence-based public health policy with special emphasis on
      guidelines creation for high-cost medicines. We also describe how that strategy
      was diffused to the judiciary system and to other parts of the healthcare system.
      RESULTS: We present an 11-year follow-up of a national project for creating and
      updating guidelines for high-cost medicines in Brazil. A total of 109 national
      guidelines were published (new or updated versions) for 66 selected diseases, the
      first such effort in Brazilian history. The project influenced the Brazilian
      legislature, which has recently established a Federal Law requiring national
      guidelines for any new technology listed for payment by the Brazilian public
      healthcare system. CONCLUSION: We were able to involve many different
      stakeholders in a partnership between academia and policy makers, which made
      possible the widespread dissemination of the clinical practice guidelines.
      Problems and constraints were also encountered. This evolving public health
      strategy might be useful for other developing countries.

PMID- 23552017
TI  - A study of hydrogen microstructure in amorphous silicon via inversion of nuclear
      magnetic resonance spectra.
AB  - We present an inverse approach for studying hydrogen microstructure in amorphous
      silicon. The approach consists of generating a prior distribution (of
      spins/hydrogen) by inverting experimental nuclear magnetic resonance (NMR) data,
      which is subsequently superimposed on a network of amorphous silicon. The
      resulting network is then relaxed using a total-energy functional to obtain a
      stable, low-energy configuration such that the initial spin distribution is
      minimally perturbed. The efficacy of this approach is demonstrated by generating
      model configurations that not only have the correct NMR spectra but also satisfy
      simultaneously experimental structural, electronic and vibrational properties of
      hydrogenated amorphous silicon.

PMID- 23552018
TI  - Prenatal immune activation interacts with stress and corticosterone exposure
      later in life to modulate N-methyl-D-aspartate receptor synaptic function and
      plasticity.
AB  - Prenatal infection is an environmental risk factor for schizophrenia while later
      in life, stressful events have been associated with the onset and severity of
      psychosis. Recent findings on the impact of stress on the N-methyl-d-aspartate
      receptor (NMDAR), of which hypofunctioning is implicated in schizophrenia,
      suggest changes in stress-induced regulation of the glutamatergic system may be
      related to the pathogenesis of schizophrenia. Our study aimed to test whether
      prenatal immune activation could interact with stress at adolescence to alter
      NMDAR function. We used offspring from rat dams administered bacterial
      lipopolysaccharide (LPS) during pregnancy (gestational days 15 and 16), an animal
      model expressing schizophrenia-related behavioural phenotypes. Using
      electrophysiological techniques, we investigated effects of stress and the stress
      hormone corticosterone (Cort) on NMDAR-mediated synaptic function and long-term
      depression (LTD) in hippocampal CA1 slices from these adolescent (aged 28-39 d)
      male offspring. In prenatal LPS offspring, NMDAR-mediated synaptic function and
      LTD were reduced and abolished, respectively, compared to prenatal saline
      controls. Notably, in vivo stress and in vitro Cort treatment facilitated LTD in
      slices from prenatal LPS rats but not prenatal saline controls. Finally, Cort
      enhanced NMDAR-mediated synaptic function in slices from prenatal LPS rats only.
      We conclude that prenatal immune activation results in NMDAR hypofunction in the
      hippocampus of adolescent rats but also increases responsiveness of NMDAR
      mediated synaptic function and LTD towards stress. Prenatal infection could
      confer susceptibility to schizophrenia through modification of hippocampal NMDAR
      function, with hypofunction in resting conditions and heightened responsiveness
      to stress, thus impacting the development of the disorder. 

PMID- 23552019
TI  - Improved hypothermic short-term storage of isolated mouse islets by adding serum
      to preservation solutions.
AB  - Preserving isolated islets at low temperature appears attractive because it can
      keep islet quantity comparable to freshly isolated islets. In this study, we
      evaluated the effect of serum as an additive to preservation solutions on islet
      quality after short-term hypothermic storage. Isolated mouse islets were
      preserved at 4 degrees C in University of Wisconsin solution (UW) alone, UW with
      serum, M-Kyoto solution (MK) alone or MK with serum. We then assessed islet
      quantity, morphology, viability and function in vitro as well as in vivo. Islet
      quantity after storage in all four solutions was well maintained for up to 120 h.
      However, islets functioned for different duration; glucose-stimulated insulin
      release assay revealed that the duration was 72 h when islets were stored in UW
      with serum and MK with serum, but only 24 h in UW alone, and the islet function
      disappeared immediately in MK alone. Viability assay confirmed that more than 70%
      islet cells survived for up to 48 h when islets are preserved in UW with serum
      and MK with serum, but the viability decreased rapidly in UW alone and MK alone.
      In in vivo bioassays using 48-h preserved isogeneic islets, all recipient mice
      restored normal blood glucose concentrations by transplants preserved in UW with
      serum or MK with serum, whereas 33.3% recipients and no recipient restored
      diabetes by transplants preserved in UW alone and in MK alone respectively.
      Adding serum to both UW and MK improves their capability to store isolated islets
      by maintaining islet functional viability.

PMID- 23552020
TI  - A population-based study of associations between functional gastrointestinal
      disorders and psychosocial characteristics in Xi'an, China.
AB  - BACKGROUND: Functional gastrointestinal disorders (FGIDs) are disorders with
      chronic and recurring gastrointestinal symptoms. This study investigated the
      prevalence of FGIDs, assessed the association between FGIDs and psychosocial
      factors, and identified potential risk factors for FGIDs in a population in
      Xi'an, China. METHODS: Of 752 recruited residents in Xi'an, 720 were selected for
      an epidemiological survey using a cluster sampling method. All subjects were
      interviewed face-to-face to complete the Chinese version of ROME III FGIDs
      questionnaire, the Symptom Check-List-90, the Eysenck Personality Questionnaire,
      a Life Event Scale, and a questionnaire regarding personal childhood adversity.
      The prevalence of FGIDs and associations between FGIDs and psychosocial factors
      were determined using EpiData Software. Logistic regression analysis was
      performed to identify the potential risk factors for FGIDs. KEY RESULTS: The
      prevalence of FGIDs in this sample population was 14.3% (103/720). There were 13
      (1.8%) cases of overlap of different FGIDs. No significant difference in the
      prevalence of FGIDs was observed between men and women. Alcohol intake and
      smoking habits were significantly associated with the presence of FGIDs. The
      presence of FGIDs was significantly associated with psychological factors and
      influences such as personality type, life events, childhood adversity, and
      psychopathology. The potential risk factors for contracting FGIDs were certain
      life events, childhood adversity, somatization, and a hostile affect (P < 0.001).
      CONCLUSIONS & INFERENCES: The prevalence of FGIDs and overlap syndrome in Xi'an,
      China was lower than that reported in other countries. There was a strong
      correlation between specific lifestyle habits and psychosocial characteristics
      and the presence of FGIDs.

PMID- 23552021
TI  - Prevalence of pterygium in a population in Northern Japan: the Locomotive
      Syndrome and Health Outcome in Aizu Cohort Study.
AB  - PURPOSE: The aim of the study was to determine the prevalence and risk factors
      for pterygium in a population aged 40-74 years in Fukushima Prefecture, Japan.
      METHODS: Of 4185 citizens of the towns of Minamiaizu-machi and Tadami-machi, 2312
      (55.2%) gave consent to an ocular examination during a health examination.
      Pterygium was diagnosed when a radially oriented fibrovascular lesion growing
      over the limbus into the cornea was observed. Eyes with a history of pterygium
      excision were also diagnosed with pterygium. Prevalence and factors associated
      with pterygium were investigated. RESULTS: Of the 2312 subjects, 101 (4.4%; 95%
      confidence interval, 3.6-5.3%) had pterygium in at least 1 eye. The average age
      (+/-SD) of the subjects was 64.3 +/- 8.0 years. Gender, age, outdoor job history
      and smoking history were examined as possible associated factors, but only age
      was found to be significantly associated with pterygium in logistic regression
      analysis. CONCLUSION: The prevalence of pterygium was 4.4% in the study
      population. This low rate may be due to the northern latitude of these towns. Age
      was associated with a risk of pterygium, but gender and outdoor job history were
      not associated with onset of pterygium in this study.

PMID- 23552022
TI  - Implant-supported oral rehabilitation of a patient with pemphigus vulgaris: a
      clinical report.
AB  - Pemphigus vulgaris (PV) is a rare mucocutaneous vesiculobullous disease
      characterized by the development of autoantibodies against the desmosomal
      proteins. Current treatment is largely based on systemic immunosuppression using
      systemic corticosteroids. Immunosuppressive drugs used in the treatment of the
      disease may increase the risk of infection and delayed healing, which are of
      concern in dental treatment procedures in this group of patients. The clinical
      outcomes of implants in PV have not been investigated. We present a case of PV
      rehabilitated with an implant-supported prosthesis with a 32-month follow-up and
      discuss the important points in the surgical and prosthodontic phases. 

PMID- 23552024
TI  - Eating at the right time of day: an underappreciated lifestyle therapy for
      hypertension?

PMID- 23552023
TI  - Mobile phone text message intervention to reduce binge drinking among young
      adults: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Heavy episodic (binge) drinking is common among young adults and can
      lead to injury and illness. Young adults who seek care in the Emergency
      Department (ED) may be disproportionately affected with binge drinking behavior,
      therefore provide an opportunity to reduce future risk through screening, brief
      intervention and referral to treatment (SBIRT). Mobile phone text messaging (SMS)
      is a common form of communication among young adults and has been shown to be
      effective at providing behavioral support to young adult drinkers after ED
      discharge. Efficacy of SMS programs to reduce binge drinking remains unknown.
      METHODS/DESIGN: We will conduct a three parallel arm, randomized trial. A
      convenience sample of adults aged 18 to 25 years attending three EDs in
      Pittsburgh, PA and willing to participate in the study will be screened for
      hazardous alcohol consumption. Participants identified as hazardous drinkers will
      then be allocated to either 12 weeks of weekly SMS drinking assessments with
      feedback (SA+F), SMS drinking assessments without feedback (SA), or a control
      group. Randomization will be via an independent and remote computerized
      randomization and will be stratified by study site. The SA+F group will be asked
      to provide pre-weekend drinking intention as well as post-weekend consumption via
      SMS and will receive feedback messages focused on health consequences of alcohol
      consumption, personalized normative feedback, protective drinking strategies and
      goal setting. Follow-up data on alcohol use and injury related to alcohol will be
      collected through a password-protected website three, six and nine months later.
      The primary outcome for the study is binge drinking days (>=4 drinks for women;
      >=5 drinks for men) during the previous month, and the main secondary outcome is
      the proportion of participants who report any injury related to alcohol in the
      prior three months. DISCUSSION: This study will test the hypothesis that a mobile
      phone text-messaging program will result in immediate and durable reductions in
      binge drinking among at-risk young adults. By testing an intervention group to an
      assessment-only and control group, we will be able to separate the effect of
      assessment reactivity. By collecting pre-weekend drinking intentions and post
      weekend consumption data in the SA+F group, we will be able to better understand
      mechanism of change. TRIAL REGISTRATION: Clinicaltrials.gov NCT01688245.

PMID- 23552025
TI  - Assessing sodium sensitivity in clinical practice: new insights from ambulatory
      blood pressure monitoring data.

PMID- 23552026
TI  - Homocysteine and the very elderly: is there a message for cardiovascular risk?

PMID- 23552027
TI  - Slum living and hypertension in tropical settings: neglected issue, statistical
      artifact or surprisingly slight? Insights amidst adversity.

PMID- 23552028
TI  - The need for hospitalization still represents a major burden for hypertensive
      patients and healthcare systems.

PMID- 23552029
TI  - Selenium and hypertension: do we need to reconsider selenium supplementation in
      cancer patients?

PMID- 23552030
TI  - Selenium and hypertension: do we need to reconsider selenium supplementation in
      cancer patients?

PMID- 23552031
TI  - Bone marrow cell therapy in hypertensive kidney disease: contribution to cardiac
      fibrosis?

PMID- 23552032
TI  - Response to Van Koppen et al.

PMID- 23552033
TI  - Angiotensin II type 1 and type 2 receptor interplay in hypertension: lesson from
      a human model of vascular hyporeactivity.

PMID- 23552034
TI  - Response to 'Angiotensin II type 1 and type 2 receptor interplay in hypertension:
      lesson from a human model of vascular hyporeactivity'.

PMID- 23552035
TI  - Is allometry really a panacea for the shortcomings of flow-mediated dilation?

PMID- 23552036
TI  - Reply to Stoner et al. regarding 'A new approach to improve the specificity of
      flow-mediated dilation for indicating endothelial function in cardiovascular
      research'.

PMID- 23552038
TI  - Experts recommend against calcitonin-salmon for postmenopausal osteoporosis.

PMID- 23552039
TI  - Diligence needed during transition in heparin products' labels.

PMID- 23552040
TI  - PTCB plans major update to certification requirements.

PMID- 23552041
TI  - Estimating depletion time for elastomeric pumps during pharmacist rounds.

PMID- 23552042
TI  - Elective course for pharmacy students on practice-based learning taught by
      pharmacy residents and fellows.

PMID- 23552043
TI  - Pharmacist integration into cardiac arrest response teams.

PMID- 23552044
TI  - Testing the predictive ability of the "spinal cord injury equation" in estimating
      vancomycin clearance.
AB  - PURPOSE: A new method of estimating drug clearance in patients with spinal cord
      injury (SCI) was tested against other methods through a retrospective analysis of
      its predictive ability in estimating vancomycin clearance. METHODS: A
      retrospective chart-based investigation was conducted at a hospital with a large
      SCI population. Using data collected from electronic patient records, 179 cases
      were reviewed, and 87 cases met the inclusion criteria: a diagnosis of
      longstanding SCI, administration of vancomycin via i.v. infusion during the 18
      month study period, and at least one documented steady-state vancomycin
      concentration. Using the "spinal cord injury equation" (i.e., CL(SCI) equation),
      pharmacokinetic analysis was performed to determine patient-specific clearance
      values, which were compared to values resulting from five widely used methods of
      estimating the glomerular filtration rate in spinal cord-injured patients. The
      primary outcome measures were bias and precision, as indicated by statistical
      analyses to determine the mean prediction error (ME) and the square root of the
      mean squared prediction error (RMSE) of each method. RESULTS: Compared with the
      other evaluated methods, the CL(SCI) equation was found to be less biased and
      more precise, with the smallest calculated ME and RMSE values (p < 0.05). The
      five alternative methods significantly overestimated vancomycin clearance, by 45
      92% (p < 0.05). The CL(SCI) method underestimated vancomycin clearance (by 6%)
      but not to a significant degree (p = 0.06). CONCLUSION: The study results suggest
      that the CL(SCI) equation for predicting vancomycin clearance was unbiased and
      may be more precise relative to other frequently used methods in the study
      population of patients with long-term SCI.

PMID- 23552045
TI  - Perspectives on the global evolution and development of pharmacy.

PMID- 23552046
TI  - Quality-improvement analytics for intravenous infusion pumps.
AB  - PURPOSE: The implementation of a smart-pump continuous quality-improvement (CQI)
      program across a large health system is described, with an emphasis on key
      metrics for outcomes analyses and program refinement. SUMMARY: Three years ago,
      the University of Pittsburgh Medical Center health system launched a CQI
      initiative to help ensure the safe use of 6000 smart pumps in its 14 inpatient
      facilities. A centralized team led by pharmacists is responsible for the
      retrieval and interpretation of smart-pump data, which is continuously
      transmitted to a main server. CQI findings are regularly posted on the health
      system's interdisciplinary intranet. Monitored metrics include rates of
      compliance with preprogrammed infusion limits, the top 20 drugs involved in
      alerts, drugs associated with alert-override rates of >=90%, numbers of alerts by
      infusion type, nurse responses to alerts, and alert rate per drug library update.
      Based on the collected CQI data and site-specific requests, four systemwide
      updates of the smart-pump drug library were performed during the first 18 months
      of the program, reducing "nuisance alerts" by about 10% per update cycle and
      enabling targeted interventions to reduce rapid-infusion errors, other adverse
      drug events (ADEs), and pump-programming workarounds. Over one 12-month period,
      bedside alerts prompted nurses to reprogram or cancel continuous infusions an
      average of 400 times per month, potentially averting i.v. medication ADEs.
      CONCLUSION: A smart-pump CQI program is an effective tool for enhancing the
      safety of i.v. medication administration. The ongoing refinement of the drug
      library through the development and implementation of key interventions promotes
      the growth and sustainability of the smart-pump initiative systemwide.

PMID- 23552047
TI  - Actions of the ASHP Board of Directors--meeting of January 11, 2013.

PMID- 23552048
TI  - ASHP professional policy recommendations--invitation to comment.

PMID- 23552049
TI  - A pilot project using evidence-based clinical pathways and payment reform in
      China's rural hospitals shows early success.
AB  - Reforming China's public hospitals to curb widespread overtreatment and improve
      the quality and affordability of care has been the most challenging aspect of
      that nation's ambitious health reform, which began in 2009. This article
      describes a pilot project under way in several of China's provinces that combines
      payment reform with the implementation of evidence-based clinical pathways at a
      few hospitals serving rural areas. Results to date include reduced length-of-stay
      and prescription drug use and higher patient and provider satisfaction. These
      early results suggest that the pilot may be achieving its goals, which may have
      far-reaching and positive implications for China's ongoing reform.

PMID- 23552050
TI  - Bidirectional relationships between cigarette use and spinal pain in adolescents
      accounting for psychosocial functioning.
AB  - OBJECTIVES: The objective of this study was to determine the presence of possible
      bidirectional causal pathways between cigarette use and spinal pain in
      adolescents controlling for psychosocial functioning, using a prospective
      longitudinal research design. DESIGN: The data for this study was collected from
      a cohort of Australian adolescents at 14 (n = 1596) and 17 (n = 1291) years of
      age. METHODS: Multivariable logistic regression was used to assess i) if
      cigarette use at 14 predicted low back pain (LBP), mid back pain (MBP) or neck
      shoulder pain (NSP) at 17 in those adolescents without each condition at 14, and
      ii) if back pain only (BP), neck shoulder pain only (NSP) or comorbid BP and NSP
      at 14 predicted cigarette use at 17 in those adolescents who did not smoke at 14.
      RESULTS: After controlling for psychosocial factors, cigarette use at 14
      predicted MBP at 17 (OR = 3.05, p = 0.049, 95% CI [1.01-9.24]). BP only at 14 was
      a significant risk factor for smoking at 17 (OR = 1.84, p = 0.006, 95% CI [1.19
      2.84]) after controlling for psychosocial factors. CONCLUSION: The findings
      indicate that there are bi-directional relationships between cigarette use and
      spinal pain and that these relationships vary with pain location.

PMID- 23552051
TI  - Binding of curcumin to milk proteins increases after static high pressure
      treatment of skim milk.
AB  - Curcumin is a bioactive polyphenolic compound extracted from turmeric with known
      anti-inflammatory properties, and its hydrophobic nature restricts its solubility
      and its bioaccessibility. Solubility may be improved upon binding of curcumin to
      native or treatment-modified casein micelles. The present work demonstrated that
      high hydrostatic pressure treatment of skim milk increases the binding of
      curcumin to caseins. The association of curcumin to casein micelles was assessed
      using fluorescence spectroscopy, either directly or by tryptophan quenching. The
      amount of curcumin associated with the milk proteins increased in pressure
      treated milk, and a further improvement in the amount of bound curcumin was
      observed upon pressure treatment of a milk/curcumin mixture. However, in this
      case, some of the curcumin dissociated during storage, contrarily to what was
      observed for untreated milk. From a molecular standpoint, the data presented here
      indicate that structural modifications induced by high-pressure treatment and
      known to affect the structure of milk proteins result in a rearrangement of the
      amino acid residues in close proximity to the protein-associated curcumin.

PMID- 23552053
TI  - A comparison of rat SPECT images obtained using (99m)Tc derived from 99Mo
      produced by an electron accelerator with that from a reactor.
AB  - Recent shortages of molybdenum-99 ((99)Mo) have led to an examination of
      alternate production methods that could contribute to a more robust supply. An
      electron accelerator and the photoneutron reaction were used to produce (99)Mo
      from which technetium-99m ((99m)Tc) is extracted. SPECT images of rat anatomy
      obtained using the accelerator-produced (99m)Tc with those obtained using (99m)Tc
      from a commercial generator were compared. Disks of (100)Mo were irradiated with
      x-rays produced by a 35 MeV electron beam to generate about 1110 MBq (30 mCi) of
      (99)Mo per disk. After target dissolution, a NorthStar ARSII unit was used to
      separate the (99m)Tc, which was subsequently used to tag pharmaceuticals suitable
      for cardiac and bone imaging. SPECT images were acquired for three rats and
      compared to images for the same three rats obtained using (99m)Tc from a standard
      reactor (99)Mo generator. The efficiency of (99)Mo-(99m)Tc separation was
      typically greater than 90%. This study demonstrated the delivery of (99m)Tc from
      the end of beam to the end user of approximately 30 h. Images obtained using the
      heart and bone scanning agents using reactor and linac-produced (99m)Tc were
      comparable. High-power electron accelerators are an attractive option for
      producing (99)Mo on a national scale.

PMID- 23552052
TI  - Selenium and prostate cancer prevention: insights from the selenium and vitamin E
      cancer prevention trial (SELECT).
AB  - The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to
      assess the efficacy of selenium and vitamin E alone, and in combination, on the
      incidence of prostate cancer. This randomized, double-blind, placebo-controlled,
      2 * 2 factorial design clinical trial found that neither selenium nor vitamin E
      reduced the incidence of prostate cancer after seven years and that vitamin E was
      associated with a 17% increased risk of prostate cancer compared to placebo. The
      null result was surprising given the strong preclinical and clinical evidence
      suggesting chemopreventive activity of selenium. Potential explanations for the
      null findings include the agent formulation and dose, the characteristics of the
      cohort, and the study design. It is likely that only specific subpopulations may
      benefit from selenium supplementation; therefore, future studies should consider
      the baseline selenium status of the participants, age of the cohort, and genotype
      of specific selenoproteins, among other characteristics, in order to determine
      the activity of selenium in cancer prevention.

PMID- 23552054
TI  - Finding novel pharmaceuticals in the systems biology era using multiple effective
      drug targets, phenotypic screening and knowledge of transporters: where drug
      discovery went wrong and how to fix it.
AB  - Despite the sequencing of the human genome, the rate of innovative and successful
      drug discovery in the pharmaceutical industry has continued to decrease. Leaving
      aside regulatory matters, the fundamental and interlinked intellectual issues
      proposed to be largely responsible for this are: (a) the move from 'function
      first' to 'target-first' methods of screening and drug discovery; (b) the belief
      that successful drugs should and do interact solely with single, individual
      targets, despite natural evolution's selection for biochemical networks that are
      robust to individual parameter changes; (c) an over-reliance on the rule-of-5 to
      constrain biophysical and chemical properties of drug libraries; (d) the general
      abandoning of natural products that do not obey the rule-of-5; (e) an incorrect
      belief that drugs diffuse passively into (and presumably out of) cells across the
      bilayers portions of membranes, according to their lipophilicity; (f) a
      widespread failure to recognize the overwhelmingly important role of
      proteinaceous transporters, as well as their expression profiles, in determining
      drug distribution in and between different tissues and individual patients; and
      (g) the general failure to use engineering principles to model biology in
      parallel with performing 'wet' experiments, such that 'what if?' experiments can
      be performed in silico to assess the likely success of any strategy. These
      facts/ideas are illustrated with a reasonably extensive literature review.
      Success in turning round drug discovery consequently requires: (a) decent systems
      biology models of human biochemical networks; (b) the use of these (iteratively
      with experiments) to model how drugs need to interact with multiple targets to
      have substantive effects on the phenotype; (c) the adoption of polypharmacology
      and/or cocktails of drugs as a desirable goal in itself; (d) the incorporation of
      drug transporters into systems biology models, en route to full and multiscale
      systems biology models that incorporate drug absorption, distribution, metabolism
      and excretion; (e) a return to 'function-first' or phenotypic screening; and (f)
      novel methods for inferring modes of action by measuring the properties on system
      variables at all levels of the 'omes. Such a strategy offers the opportunity of
      achieving a state where we can hope to predict biological processes and the
      effect of pharmaceutical agents upon them. Consequently, this should both lower
      attrition rates and raise the rates of discovery of effective drugs
      substantially.

PMID- 23552055
TI  - Influence of the layer thickness in plasmonic gold nanoparticles produced by
      thermal evaporation.
AB  - Metallic nanoparticles (NPs) have received recently considerable interest of
      photonic and photovoltaic communities. In this work, we report the optoelectronic
      properties of gold NPs (Au-NPs) obtained by depositing very thin gold layers on
      glass substrates through thermal evaporation electron-beam assisted process. The
      effect of mass thickness of the layer was evaluated. The polycrystalline Au-NPs,
      with grain sizes of 14 and 19 nm tend to be elongated in one direction as the
      mass thickness increase. A 2 nm layer deposited at 250 degrees C led to the
      formation of Au-NPs with 10-20 nm average size, obtained by SEM images, while for
      a 5 nm layer the wide size elongates from 25 to 150 nm with a mean at 75 nm. In
      the near infrared region was observed an absorption enhancement of amorphous
      silicon films deposited onto the Au-NPs layers with a corresponding increase in
      the PL peak for the same wavelength region.

PMID- 23552058
TI  - Assessing the international use of health technology assessments: exploring the
      merits of different methods when applied to the National Institute of Health
      Research Health Technology Assessment (NIHR HTA) programme.
AB  - OBJECTIVES: This study presents findings from a study that explores the merits of
      different methods for assessing the international use of UK funded research by
      the National Institute of Health Research Health Technology Assessment (NIHR HTA)
      Programme. METHODS: The study adopted an exploratory approach and used three core
      methods: (i) Academic use was explored through bibliometric and citation analysis
      of the top ten most cited health technology assessment (HTA) reports. (ii)
      Internet use was assessed using Webtrends software to identify the proportion of
      international visits of the top ten most downloaded HTA reports from January 1,
      2004 to June 30, 2010. (iii) International HTA use was assessed by searching the
      Center for Reviews and Dissemination (CRD) HTA database to explore the citation
      of NIHR HTA reports in reports by non-UK HTA agencies. RESULTS: Bibliometric
      analysis identified published output and international citations with 41 percent
      of the 549 journals citing NIHR HTA reports being based in the United States.
      Nine of ten most downloaded reports from the NIHR HTA Web site (www.hta.ac.uk)
      had in excess of 50 percent of visits outside the United Kingdom. Four of five
      selected NIHR HTA reports were cited in twenty-eight other HTA reports, eighteen
      of these outside the United Kingdom. CONCLUSIONS: Assessing international use is
      important when exploring the uptake of research evidence. Methods used in
      identifying research impact, such as bibliometrics and Webtrends, are helpful in
      generating evidence of international use. HTA agencies should consider these
      techniques and international use when assessing the uptake of findings from
      research they undertake and/or commission.

PMID- 23552056
TI  - Extensive circadian and light regulation of the transcriptome in the malaria
      mosquito Anopheles gambiae.
AB  - BACKGROUND: Mosquitoes exhibit 24 hr rhythms in flight activity, feeding,
      reproduction and development. To better understand the molecular basis for these
      rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized
      microarray analysis on time-of-day specific collections of mosquitoes over 48 hr
      to explore the coregulation of gene expression rhythms by the circadian clock and
      light, and compare these with the 24 hr rhythmic gene expression in the diurnal
      Aedes aegypti dengue vector mosquito. RESULTS: In time courses from An. gambiae
      head and body collected under light:dark cycle (LD) and constant dark (DD)
      conditions, we applied three algorithms that detect sinusoidal patterns and an
      algorithm that detects spikes in expression. This revealed across four
      experimental conditions 393 probes newly scored as rhythmic. These genes
      correspond to functions such as metabolic detoxification, immunity and nutrient
      sensing. This includes glutathione S-transferase GSTE5, whose expression pattern
      and chromosomal location are shared with other genes, suggesting shared
      chromosomal regulation; and pulsatile expression of the gene encoding CYP6M2, a
      cytochrome P450 that metabolizes pyrethroid insecticides. We explored the
      interaction of light and the circadian clock and highlight the regulation of
      odorant binding proteins (OBPs), important components of the olfactory system. We
      reveal that OBPs have unique expression patterns as mosquitoes make the
      transition from LD to DD conditions. We compared rhythmic expression between An.
      gambiae and Ae. aegypti heads collected under LD conditions using a single cosine
      fitting algorithm, and report distinct similarities and differences in the
      temporal regulation of genes involved in tRNA priming, the vesicular-type ATPase,
      olfaction and vision between the two species. CONCLUSIONS: These data build on
      our previous analyses of time-of-day specific regulation of the An. gambiae
      transcriptome to reveal additional rhythmic genes, an improved understanding of
      the co-regulation of rhythms in gene expression by the circadian clock and by
      light, and an understanding of the time-of-day specific regulation of some of
      these rhythmic processes in comparison with a different species of mosquito.
      Improved understanding of biological timing at the molecular level that underlies
      key physiological aspects of mosquito vectors may prove to be important to
      successful implementation of established and novel insect control methods.

PMID- 23552057
TI  - Gliotoxin-induced changes in rat liver regeneration after partial hepatectomy.
AB  - BACKGROUND: Hepatic non-parenchymal cells (NPCs), encompassing hepatic stellate
      cells (HSCs), macrophages and endothelial cells, synthesize new hepatocyte growth
      factor (HGF) during liver regeneration (LR), and also play an important function
      in matrix production at the end of regeneration. AIMS: The aim of this study was
      to determine whether ablating NPCs either during hepatocyte proliferation or
      during matrix resynthesis will have any effect on LR. METHODS: Rats were injected
      with either gliotoxin (which induces NPC apoptosis) or vehicle control at various
      stages during partial hepatectomy (PH). NPCs and hepatocytes were also treated in
      vitro with gliotoxin. RESULTS: Proliferating cells were abundant in control
      livers 24 h after PH, while in gliotoxin-treated rats, mitosis was absent,
      apoptotic NPCs were apparent and HGF was decreased. In vitro studies demonstrated
      a > 50% decrease in cell viability in NPC cultures, while hepatocyte viability
      and proliferation were unaffected. Chronic elimination of NPCs over a period of 5
      days after PH led to increased desmin-positive HSCs and fewer alpha smooth muscle
      actin-expressing HSCs. Finally, there was continued proliferation of hepatocytes
      and decreased collagen I and TGF-beta when HSCs, the matrix-producing NPCs, were
      ablated during later stages of LR. CONCLUSIONS: Ablation of NPCs at early time
      points after PH interferes with liver regeneration, while their ablation at late
      stages causes impairment in the termination of LR, demonstrating a time-dependent
      regulatory role of NPCs in the regenerative process.

PMID- 23552059
TI  - A chronic model of arthritis supported by a strain-specific periarticular lymph
      node in BALB/c mice.
AB  - Current animal models of arthritis only partially reflect the complexity of
      rheumatoid arthritis and typically lack either chronicity or autoantibody
      formation. Here we describe a model that combines features of antigen-induced
      arthritis and collagen-induced arthritis, which can be efficiently induced in
      BALB/c and C57BL/6 mice. However, BALB/c mice generate significantly higher
      titres of anticollagen and anticitrullinated peptide antibodies, show a stronger
      progressive joint destruction, and in the chronic phase the disease spreads
      between joints. Concomitant to the observation of a more severe pathology, we
      discovered a previously undescribed small periarticular lymph node in close
      proximity to the knee joint of BALB/c mice, which acts as the primary draining
      lymph node for the synovial cavity. Our model more closely reflects the pathology
      of rheumatoid arthritis than classical models of arthritis and is hence
      particularly suitable for further studies of disease pathogenesis.

PMID- 23552060
TI  - Dawn-dusk asymmetry in the Kelvin-Helmholtz instability at Mercury.
AB  - The NASA MErcury Surface, Space ENvironment, GEochemistry and Ranging (MESSENGER)
      spacecraft entered orbital phase around Mercury on 18 March 2011. A surprising
      consistent feature in the data returned is large-scale vortices that form
      exclusively on the dusk side of the magnetosphere. Here we present global kinetic
      hybrid simulations that explain these observations. It is shown that vortices are
      excited by a Kelvin-Helmholtz instability near the subsolar point, which grows
      convectively along the dusk-side magnetopause. Virtual time series along a track
      approximating a flyby of the MESSENGER show correspondence with the satellite
      data; the data contain sawtooth oscillations in plasma density, flow and magnetic
      field, and exhibit the observed dawn-dusk asymmetry. It is shown that asymmetry
      between dawn and dusk at Mercury is controlled by the finite gyroradius of ions
      and by convection electric fields. Mercury's magnetosphere offers a natural
      laboratory for studying plasma regimes not present in other planetary
      magnetospheres or the laboratory.

PMID- 23552061
TI  - Interplay of Dirac fermions and heavy quasiparticles in solids.
AB  - Many-body interactions in crystalline solids can be conveniently described in
      terms of quasiparticles with strongly renormalized masses as compared with those
      of non-interacting particles. Examples of extreme mass renormalization are on the
      one hand graphene, where the charge carriers obey the linear dispersion relation
      of massless Dirac fermions, and on the other hand heavy-fermion materials where
      the effective electron mass approaches the mass of a proton. Here we show that
      both extremes, Dirac fermions, like they are found in graphene and extremely
      heavy quasiparticles characteristic for Kondo materials, may not only coexist in
      a solid but can also undergo strong mutual interactions. Using the example of
      EuRh2Si2, we explicitly demonstrate that these interactions can take place at the
      surface and in the bulk. The presence of the linear dispersion is imposed solely
      by the crystal symmetry, whereas the existence of heavy quasiparticles is caused
      by the localized nature of the 4f states.

PMID- 23552062
TI  - Two-dimensional structure from random multiparticle X-ray scattering images using
      cross-correlations.
AB  - Knowledge of the structure of biological macromolecules, especially in their
      native environment, is crucial because of the close structure-function
      relationship. X-ray small-angle scattering is used to determine the shape of
      particles in solution, but the achievable resolution is limited owing to
      averaging over particle orientations. In 1977, Kam proposed to obtain additional
      structural information from the cross-correlation of the scattering intensities.
      Here we develop the method in two dimensions, and give a procedure by which the
      single-particle diffraction pattern is extracted in a model-independent way from
      the correlations. We demonstrate its application to a large set of synchrotron X
      ray scattering images on ensembles of identical, randomly oriented particles of
      350 or 200 nm in size. The obtained 15 nm resolution in the reconstructed shape
      is independent of the number of scatterers. The results are discussed in view of
      proposed 'snapshot' scattering by molecules in the liquid phase at X-ray free
      electron lasers.

PMID- 23552063
TI  - Photochemical activity of Titan's low-altitude condensed haze.
AB  - Titan, the largest moon of Saturn and similar to Earth in many aspects, has
      unique orange-yellow colour that comes from its atmospheric haze, whose formation
      and dynamics are far from well understood. Present models assume that Titan's
      tholin-like haze formation occurs high in atmosphere through gas-phase chemical
      reactions initiated by high-energy solar radiation. Here we address an important
      question: Is the lower atmosphere of Titan photochemically active or inert? We
      demonstrate that indeed tholin-like haze formation could occur on condensed
      aerosols throughout the atmospheric column of Titan. Detected in Titan's
      atmosphere, dicyanoacetylene (C4N2) is used in our laboratory simulations as a
      model system for other larger unsaturated condensing compounds. We show that C4N2
      ices undergo condensed-phase photopolymerization (tholin formation) at
      wavelengths as long as 355 nm pertinent to solar radiation reaching a large
      portion of Titan's atmosphere, almost close to the surface.

PMID- 23552064
TI  - Quantum engineering at the silicon surface using dangling bonds.
AB  - Individual atoms and ions are now routinely manipulated using scanning tunnelling
      microscopes or electromagnetic traps for the creation and control of artificial
      quantum states. For applications such as quantum information processing, the
      ability to introduce multiple atomic-scale defects deterministically in a
      semiconductor is highly desirable. Here we use a scanning tunnelling microscope
      to fabricate interacting chains of dangling bond defects on the hydrogen
      passivated silicon (001) surface. We image both the ground-state and the excited
      state probability distributions of the resulting artificial molecular orbitals,
      using the scanning tunnelling microscope tip bias and tip-sample separation as
      gates to control which states contribute to the image. Our results demonstrate
      that atomically precise quantum states can be fabricated on silicon, and suggest
      a general model of quantum-state fabrication using other chemically passivated
      semiconductor surfaces where single-atom depassivation can be achieved using
      scanning tunnelling microscopy.

PMID- 23552065
TI  - Direct visualization of reversible dynamics in a Si6 cluster embedded in a
      graphene pore.
AB  - Clusters containing only a handful of atoms have been the subject of extensive
      theoretical and experimental studies, but their direct imaging has not been
      possible so far, with information about their structure provided mainly by
      theory. Here we report a direct atomically-resolved observation of a single Si6
      cluster trapped in a graphene nanopore. Furthermore, though electron-beam-induced
      irreversible atomic displacements have been reported before, here we report a
      sequence of images that show a reversible, oscillatory, conformational change:
      one of the Si atoms jumps back and forth between two different positions. Density
      functional calculations show that the embedded cluster is exploring metastable
      configurations under the influence of the beam, providing direct information on
      the atomic-scale energy landscape. The capture of a Si cluster in a graphene
      nanopore suggests the possibility of patterning nanopores and assembling atomic
      clusters with a potential for applications.

PMID- 23552066
TI  - High-resolution correlation spectroscopy of 13C spins near a nitrogen-vacancy
      centre in diamond.
AB  - Spin complexes comprising the nitrogen-vacancy centre and neighbouring spins are
      being considered as a building block for a new generation of spintronic and
      quantum information processing devices. As assembling identical spin clusters is
      difficult, new strategies are being developed to determine individual node
      structures with the highest precision. Here we use a pulse protocol to monitor
      the time evolution of the (13)C ensemble in the vicinity of a nitrogen-vacancy
      centre. We observe long-lived time correlations in the nuclear spin dynamics,
      limited by nitrogen-vacancy spin-lattice relaxation. We use the host (14)N spin
      as a quantum register and demonstrate that hyperfine-shifted resonances can be
      separated upon proper nitrogen-vacancy initialization. Intriguingly, we find that
      the amplitude of the correlation signal exhibits a sharp dependence on the
      applied magnetic field. We discuss this observation in the context of the quantum
      to-classical transition proposed recently to explain the field dependence of the
      spin cluster dynamics.

PMID- 23552068
TI  - Reconciliation of marine and terrestrial carbon isotope excursions based on
      changing atmospheric CO2 levels.
AB  - Negative carbon isotope excursions measured in marine and terrestrial substrates
      indicate large-scale changes in the global carbon cycle, yet terrestrial
      substrates characteristically record a larger-amplitude carbon isotope excursion
      than marine substrates for a single event. Here we reconcile this difference by
      accounting for the fundamental increase in carbon isotope fractionation by land
      plants in response to increasing atmospheric CO2 concentration (pCO2). We show
      that for any change in pCO2 concentration (DeltapCO2), terrestrial and marine
      records can be used together to reconstruct background and maximum pCO2 levels
      across the carbon isotope excursion. When applied to the carbon isotope excursion
      at the Palaeocene-Eocene boundary, we calculate pCO2=674-1,034 p.p.m.v. during
      the Late Palaeocene and 1,384-3,342 p.p.m.v. during the height of the carbon
      isotope excursion across all sources postulated for the carbon release. This
      analysis demonstrates the need to account for changing pCO2 concentration when
      analysing large-scale changes in the carbon isotope composition of terrestrial
      substrates.

PMID- 23552067
TI  - Experience enhances gamma oscillations and interhemispheric asymmetry in the
      hippocampus.
AB  - Gamma oscillations are implicated in higher-order brain functions such as
      cognition and memory, but how an animal's experience organizes these gamma
      activities remains elusive. Here we show that the power of hippocampal theta
      associated gamma oscillations recorded during urethane anesthesia tends to be
      greater in rats reared in an enriched environment than those reared in an
      isolated condition. This experience-dependent gamma enhancement is consistently
      larger in the right hippocampus across subjects, coinciding with a lateralized
      increase of synaptic density in the right hippocampus. Moreover, interhemispheric
      coherence in the enriched environment group is significantly elevated at the
      gamma frequency. These results suggest that enriched rearing sculpts the
      functional left-right asymmetry of hippocampal circuits by reorganization of
      synapses.

PMID- 23552069
TI  - Microbiota-derived lactate accelerates colon epithelial cell turnover in
      starvation-refed mice.
AB  - Oral food intake influences the morphology and function of intestinal epithelial
      cells and maintains gastrointestinal cell turnover. However, how exactly these
      processes are regulated, particularly in the large intestine, remains unclear.
      Here we identify microbiota-derived lactate as a major factor inducing enterocyte
      hyperproliferation in starvation-refed mice. Using bromodeoxyuridine staining, we
      show that colonic epithelial cell turnover arrests during a 12- to 36-h period of
      starvation and increases 12-24 h after refeeding. Enhanced epithelial cell
      proliferation depends on the increase in live Lactobacillus murinus, lactate
      production and dietary fibre content. In the model of colon tumorigenesis, mice
      exposed to a carcinogen during refeeding develop more aberrant crypt foci than
      mice fed ad libitum. Furthermore, starvation after carcinogen exposure greatly
      reduced the incidence of aberrant crypt foci. Our results indicate that the
      content of food used for refeeding as well as the timing of carcinogen exposure
      influence the incidence of colon tumorigenesis in mice.

PMID- 23552070
TI  - Observations from old forests underestimate climate change effects on tree
      mortality.
AB  - Understanding climate change-associated tree mortality is central to linking
      climate change impacts and forest structure and function. However, whether
      temporal increases in tree mortality are attributed to climate change or stand
      developmental processes remains uncertain. Furthermore, interpreting the climate
      change-associated tree mortality estimated from old forests for regional forests
      rests on an un-tested assumption that the effects of climate change are the same
      for young and old forests. Here we disentangle the effects of climate change and
      stand developmental processes on tree mortality. We show that both climate change
      and forest development processes influence temporal mortality increases, climate
      change-associated increases are significantly higher in young than old forests,
      and higher increases in younger forests are a result of their higher sensitivity
      to regional warming and drought. We anticipate our analysis to be a starting
      point for more comprehensive examinations of how forest ecosystems might respond
      to climate change.

PMID- 23552072
TI  - Inhibition of return in the archer fish.
AB  - Inhibition of return is the inhibitory tagging of recently attended locations or
      objects. It was previously suggested that inhibition of return is a foraging
      facilitator in visual search. Inhibition of return was first discovered in humans
      and was demonstrated also in monkeys, yet it has never been demonstrated in non
      primates. Here we report the presence of inhibition of return in the archer fish,
      which shoots down prey on overhanging vegetation, using squirts of water spouted
      from its mouth. Moreover, we find similar attentional effects for fish as for
      human participants. Our results show that the generation of inhibition of return
      does not require a fully developed cortex and strengthen the view that inhibition
      of return functions as a foraging facilitator.

PMID- 23552071
TI  - Mass spectrometric analysis of mono- and multi-phosphopeptides by selective
      binding with NiZnFe2O4 magnetic nanoparticles.
AB  - Selective isolation of mono- and multi-phosphorylated peptides is important for
      understanding how a graded protein kinase or phosphatase signal can precisely
      modulate the on and off states of signal transduction pathways. Here we report
      that metal ions at exposed octahedral sites of nano-ferrites, including Fe3O4,
      NiFe2O4, ZnFe2O4 and NiZnFe2O4, have distinctly selective coordination abilities
      with mono- and multi- phosphopeptides. Due to their intrinsic magnetic properties
      and high surface area to volume ratios, these nanoparticles enable the rapid
      isolation of mono- and multi-phosphopeptides by an external magnetic field. Model
      phosphoprotein alpha-casein and two synthesized mono- and di-phosphopeptides have
      been chosen for proof-of-principle demonstrations, and these nanoparticles have
      also been applied to phosphoproteome profiling of zebrafish eggs. It is shown
      that NiZnFe2O4 is highly selective for multi-phosphopeptides. In contrast, Fe3O4,
      NiFe2O4 and ZnFe2O4 can bind with both mono- and multi-phosphopeptides with
      relatively stronger affinity towards mono-phosphopeptides.

PMID- 23552073
TI  - Ets2-dependent trophoblast signalling is required for gastrulation progression
      after primitive streak initiation.
AB  - Although extraembryonic ectoderm trophoblast signals the embryo for primitive
      streak initiation, a prerequisite for gastrulation, it is unknown whether it also
      signals for the progression of gastrulation after primitive streak initiation.
      Here, using Ets2-/- mice, we show that trophoblast signalling is also required in
      vivo for primitive streak elongation, completion of intraembryonic mesoderm
      epithelial-mesenchymal transition and the development of anterior primitive
      streak derivatives such as the node. We show that Ets2-dependent trophoblast
      signalling is required for the maintenance of high levels of Nodal and Wnt3
      expression in the epiblast and for the induction of Snail expression in the
      primitive streak, between embryonic day 6.3 and 6.7. Within extraembryonic
      ectoderm trophoblast, Ets2 maintains the expression of the transcription factors
      Elf5, Cdx2 and Eomes, and that of the signalling molecule Bmp4. We propose a
      model that provides a genetic explanation as to how Ets2 in trophoblast mediates
      the progression of gastrulation within the epiblast.

PMID- 23552074
TI  - Regulation of protein glycosylation and sorting by the Golgi matrix proteins
      GRASP55/65.
AB  - The Golgi receives the entire output of newly synthesized cargo from the
      endoplasmic reticulum, processes it in the stack largely through modification of
      bound oligosaccharides, and sorts it in the trans-Golgi network. GRASP65 and
      GRASP55, two proteins localized to the Golgi stack and early secretory pathway,
      mediate processes including Golgi stacking, Golgi ribbon linking and
      unconventional secretion. Previously, we have shown that GRASP depletion in cells
      disrupts Golgi stack formation. Here we report that knockdown of the GRASP
      proteins, alone or combined, accelerates protein trafficking through the Golgi
      membranes but also has striking negative effects on protein glycosylation and
      sorting. These effects are not caused by Golgi ribbon unlinking, unconventional
      secretion or endoplasmic reticulum stress. We propose that GRASP55/65 are
      negative regulators of exocytic transport and that this slowdown helps to ensure
      more complete protein glycosylation in the Golgi stack and proper sorting at the
      trans-Golgi network.

PMID- 23552076
TI  - Evidence for a material gradient in the adhesive tarsal setae of the ladybird
      beetle Coccinella septempunctata.
AB  - For an insect to be able to efficiently attach to surfaces, the adhesive pads on
      the distal parts of its legs must establish large contact areas. In case of hairy
      adhesive pads this requires flexibility of the contact-forming bristles, called
      adhesive tarsal setae. However, too flexible setae would have a low mechanical
      stability resulting in a decreased attachment ability of the pads. Here we show
      that the adhesive tarsal setae of the ladybird beetle Coccinella septempunctata
      feature pronounced gradients in the material composition and properties along
      their length. The Young's modulus ranges from 1.2 MPa at the tips, where we found
      the incorporation of high proportions of the elastic protein resilin, to 6.8 GPa
      at the bases of the setae. These gradients likely represent an evolutionary
      optimization, which increases the performance of the adhesive system by enabling
      effective adaptation to rough surfaces while simultaneously preventing lateral
      collapse of the setae.

PMID- 23552075
TI  - Klf5 controls bone marrow homing of stem cells and progenitors through Rab5
      mediated beta1/beta2-integrin trafficking.
AB  - Kruppel-like factor 5 regulates pluripotent stem cell self-renewal, but its role
      in somatic stem cells is unknown. Here we show that Kruppel-like factor 5
      deficient haematopoietic stem cells and progenitors fail to engraft after
      transplantation. This haematopoietic stem cell and progenitor defect is
      associated with impaired bone marrow homing and lodging and decreased retention
      in bone marrow, and with decreased adhesion to fibronectin and expression of
      membrane-bound beta1/beta2-integrins. In vivo-inducible gain-of-function of
      Kruppel-like factor 5 in haematopoietic stem cells increases haematopoietic stem
      cell and progenitor adhesion. The expression of Rab5 family members, mediators of
      beta1/beta2-integrin recycling in the early endosome, is decreased in
      Klf5(Delta/Delta) haematopoietic stem cells and progenitors. Kruppel-like factor
      5 binds directly to the promoter of Rab5a/b, and overexpression of Rab5b rescues
      the expression of activated beta1/beta2-integrins, adhesion and bone marrow
      homing of Klf5(Delta/Delta) haematopoietic stem cells and progenitors.
      Altogether, these data indicate that Kruppel-like factor 5 is indispensable for
      adhesion, homing, lodging and retention of haematopoietic stem cells and
      progenitors in the bone marrow through Rab5-dependent post-translational
      regulation of beta1/beta2 integrins.

PMID- 23552077
TI  - Involvement of the mentalizing network in social and non-social high construal.
AB  - The dorsomedial prefrontal cortex (dmPFC) is consistently involved in tasks
      requiring the processing of mental states, and much rarer so by tasks that do not
      involve mental state inferences. We hypothesized that the dmPFC might be more
      generally involved in high construal of stimuli, defined as the formation of
      concepts or ideas by omitting non-essential features of stimuli, irrespective of
      their social or non-social nature. In an fMRI study, we presented pictures of a
      person engaged in everyday activities (social stimuli) or of objects (non-social
      stimuli) and induced a higher level of construal by instructing participants to
      generate personality traits of the person or categories to which the objects
      belonged. This was contrasted against a lower level task where participants had
      to describe these same pictures visually. As predicted, we found strong
      involvement of the dmPFC in high construal, with substantial overlap across
      social and non-social stimuli, including shared activation in the vmPFC/OFC,
      parahippocampal, fusiform and angular gyrus, precuneus, posterior cingulate and
      right cerebellum.

PMID- 23552080
TI  - Thermally activated cation ordering in ZnGa2Se4 single crystals studied by Raman
      scattering, optical absorption, and ab initio calculations.
AB  - Order-disorder phase transitions induced by thermal annealing have been studied
      in the ordered-vacancy compound ZnGa2Se4 by means of Raman scattering and optical
      absorption measurements. The partially disordered as-grown sample with tetragonal
      defect stannite (DS) structure and I4-2m space group has been subjected to
      controlled heating and cooling cycles. In situ Raman scattering measurements
      carried out during the whole annealing cycle show that annealing the sample to
      400  degrees C results in a cation ordering in the sample, leading to the
      crystallization of the ordered tetragonal defect chalcopyrite (DC) structure with
      I4- space group. On decreasing temperature the ordered cation scheme of the DC
      phase can be retained at ambient conditions. The symmetry of the Raman-active
      modes in both DS and DC phases is discussed and the similarities and differences
      between the Raman spectra of the two phases emphasized. The ordered structure of
      annealed samples is confirmed by optical absorption measurements and ab initio
      calculations, that show that the direct bandgap of DC-ZnGa2Se4 is larger than
      that of DS-ZnGa2Se4.

PMID- 23552079
TI  - Neural correlates of reward and loss sensitivity in psychopathy.
AB  - Psychopathy is a personality disorder associated with callous and impulsive
      behavior and criminal recidivism. It has long been theorized that psychopaths
      have deficits in processing reward and punishment. Here, we use structural and
      functional magnetic resonance imaging to examine the neural correlates of reward
      and loss sensitivity in a group of criminal psychopaths. Forty-one adult male
      prison inmates (n = 18 psychopaths and n = 23 non-psychopaths) completed a
      functional magnetic resonance imaging task involving the gain or loss of money.
      Across the entire sample of participants, monetary gains elicited robust
      activation within the ventral striatum (VS). Although psychopaths and non
      psychopaths did not significantly differ with respect to overall levels of VS
      response to reward vs loss, we observed significantly different correlations
      between VS responses and psychopathy severity within each group. Volumetric
      analyses of striatal subregions revealed a similar pattern of correlations,
      specifically for the right accumbens area within VS. In a separate sample of
      inmates (n = 93 psychopaths and n = 117 non-psychopaths) who completed a self
      report measure of appetitive motivation, we again found that the correlation with
      psychopathy severity differed between groups. These convergent results offer
      novel insight into the neural substrates of reward and loss processing in
      psychopathy.

PMID- 23552078
TI  - Network structure underlying resolution of conflicting non-verbal and verbal
      social information.
AB  - Social judgments often require resolution of incongruity in communication
      contents. Although previous studies revealed that such conflict resolution
      recruits brain regions including the medial prefrontal cortex (mPFC) and
      posterior inferior frontal gyrus (pIFG), functional relationships and networks
      among these regions remain unclear. In this functional magnetic resonance imaging
      study, we investigated the functional dissociation and networks by measuring
      human brain activity during resolving incongruity between verbal and non-verbal
      emotional contents. First, we found that the conflict resolutions biased by the
      non-verbal contents activated the posterior dorsal mPFC (post-dmPFC), bilateral
      anterior insula (AI) and right dorsal pIFG, whereas the resolutions biased by the
      verbal contents activated the bilateral ventral pIFG. In contrast, the anterior
      dmPFC (ant-dmPFC), bilateral superior temporal sulcus and fusiform gyrus were
      commonly involved in both of the resolutions. Second, we found that the post
      dmPFC and right ventral pIFG were hub regions in networks underlying the non
      verbal- and verbal-content-biased resolutions, respectively. Finally, we revealed
      that these resolution-type-specific networks were bridged by the ant-dmPFC, which
      was recruited for the conflict resolutions earlier than the two hub regions.
      These findings suggest that, in social conflict resolutions, the ant-dmPFC
      selectively recruits one of the resolution-type-specific networks through its
      interaction with resolution-type-specific hub regions.

PMID- 23552081
TI  - A confirmatory factor analysis of the Self-Directed Learning Readiness Scale.
AB  - The Self-Directed Learning Readiness Scale measures readiness for self-directed
      learning among undergraduate healthcare students. While several exploratory
      factor analyses and one confirmatory factor analysis have examined the
      psychometric properties of the Self-Directed Learning Readiness Scale, questions
      have been raised regarding the underlying latent constructs being measured. The
      objective of this study was to determine the best-fitting Self-Directed Learning
      Readiness Scale factorial structure among three models published in the
      literature. Data from the three-factor 40-item Self-Directed Learning Readiness
      Scale completed by 233 undergraduate paramedic students from four Australian
      universities (response rate of 26%) were analyzed using maximum likelihood
      confirmatory factor analysis. Comparison of model fit from the 40-item version
      was undertaken with the previously documented four-factor 36-item and three
      factor 29-item Self-Directed Learning Readiness Scales. The model fit indices of
      the three one-factor congeneric models with maximum likelihood analysis
      demonstrate that the 40-item Self-Directed Learning Readiness Scale does not fit
      the data well. The best fitting model was the four-factor 36-item Self-Directed
      Learning Readiness Scale followed by the three-factor 29-item models. The
      confirmatory factor analysis results did not support the overall construct
      validity of the original 40-item Self-Directed Learning Readiness Scale. 

PMID- 23552082
TI  - Patient-centered outcomes research: evolution, definition, and implications.

PMID- 23552083
TI  - Graft orientation, optical coherence tomography, and endothelial keratoplasty.

PMID- 23552084
TI  - Reticular pseudodrusen.

PMID- 23552085
TI  - Sclerosing polycystic adenosis of the lacrimal gland.

PMID- 23552086
TI  - Residency education professionalism vignettes.

PMID- 23552087
TI  - Glaucoma progression analysis.

PMID- 23552088
TI  - Author reply: To PMID 22137043.

PMID- 23552089
TI  - Effect of axial length on diabetic retinopathy.

PMID- 23552090
TI  - Author reply: To PMID 22627119.

PMID- 23552091
TI  - Maculopathy resolution after surgery for an optic disc pit.

PMID- 23552092
TI  - Author reply: To PMID 22218142.

PMID- 23552093
TI  - Neuro-ophthalmology Safer Than MRI?

PMID- 23552094
TI  - Author reply: To PMID 22484117.

PMID- 23552095
TI  - Burden of disease due to dementia in the elderly population of Korea: present and
      future.
AB  - BACKGROUND: With the rapid aging of populations around the world, dementia has
      become one of the most important public health problems in Eastern Asian
      countries. The purpose of the present study was to provide an estimate of the
      burden of dementia and forecast its future burden, as generalized to the Korean
      population, and to provide detailed gender- and age-specific information
      regarding the burden of dementia in the elderly population of Korea. METHODS:
      'Disability-adjusted life years' (DALYs) were used to estimate the burden of
      dementia. Epidemiologic data from national statistics and nationwide
      epidemiologic studies in the year 2008 were used to obtain representative
      outcomes for the Korean population. We estimated the DALYs due to dementia from
      the years 2010 to 2050 by applying demographic structure projections in terms of
      5-year age groups in Korea. RESULTS: The burden of disease due to dementia in
      Korea is 528 per 100,000 population (males: 435, females: 622) and 5,117 per
      100,000 in those over the age of 65 years (males: 5,228; females: 5,041); this
      accounts for 4.5% of the total burden of disease in the year 2008. In the year
      2050, DALYs due to dementia (814,629) are expected to be 3.0 times higher than
      those in the year 2010 (274,849). CONCLUSION: Dementia has the highest burden of
      disease in the elderly Korean population, and this burden will increase sharply
      with the aging of the population. More comprehensive and multi-dimensional
      approaches, including clinical, psychological, social, and political means will
      be needed for the management of the dramatically increasing burden of dementia.

PMID- 23552097
TI  - A multidisciplinary approach for management of postenucleation socket syndrome
      with dermis-fat graft and ocular prosthesis: a clinical report.
AB  - A contracted eye socket is a cosmetic blemish to the patient. It not only renders
      patients unable to wear an eye prosthesis, but also becomes a source of chronic
      discharge and irritation. Orbital implants allow for cosmesis and volume
      replacement of an enucleated or eviscerated eye. Alloplastic orbital implants are
      associated with potential complications, including exposure and extrusion. A
      dermis-fat graft offers the advantages of relative availability and an autologous
      nature. This article reports on a patient suffering from severe postenucleation
      socket syndrome after enucleation of the bulbus with postoperative irradiation of
      the orbit due to retinoblastoma and its subsequent management by a dermal-fat
      graft and ocular prosthesis. The purpose of this article is to emphasize the
      usefulness of dermal-fat grafting as a safe and stable orbital volume replacement
      following enucleation. 

PMID- 23552096
TI  - Associations between prefrontal gamma-aminobutyric acid concentration and the
      tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women.
AB  - Associations between the central serotonergic and gamma-aminobutyric acid (GABA)
      systems play key roles in the prefrontal cortical regulation of emotion and
      cognition and in the pathophysiology and pharmacotherapy of highly prevalent
      psychiatric disorders. The goal of this study was to test the effects of common
      variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA
      concentration in the prefrontal cortex (PFC) using magnetic resonance
      spectroscopy. In this study involving 64 individuals, we examined the
      associations between prefrontal cortical GABA concentration and 12 single
      nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703
      G/T SNP), a potentially functional TPH2 polymorphism that has been associated
      with decreased TPH2 mRNA expression and panic disorder. Our results revealed a
      significant association between increased GABA concentration in the PFC and the T
      allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575
      (p?0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p =
      0.0003) in female subjects. We concluded that rs4570625 (-703 G/T), rs2129575 and
      rs1386491 play a significant role in GABAergic neurotransmission and may
      contribute to the sex-specific dysfunction of the GABAergic system in the PFC. 

PMID- 23552098
TI  - Retinal and choroidal intravascular spectral-domain optical coherence tomography.
AB  - PURPOSE: To examine retinal and choroidal blood vessels using spectral-domain
      optical coherence tomography (SD-OCT). METHODS: Retrospective case series.
      RESULTS: Scans through retinal blood vessels in healthy subjects demonstrated
      vessel wall reflexes and a tri-layer profile of the blood column on longitudinal
      scans and a figure-of-eight configuration on cross-sectional scans. Intravascular
      reflectivity decreased with increasingly oblique angles of observation and was
      absent when blood flow was parallel to the line of sight. The high blood flow in
      the choroidal vessels in healthy subjects and the low flow in the retinal vessels
      in patients with ocular ischaemic syndrome and central retinal artery occlusion
      were both associated with lower reflectivity of the blood and an unstructured
      intravascular SD-OCT profile. DISCUSSION: This qualitative in vivo study found a
      characteristically structured SD-OCT profile of the blood column in retinal
      vessels with normal blood flow. Both structure and total reflectivity faded when
      blood flow was lower or higher than normal or at oblique angles to the line of
      sight. In conclusion, SD-OCT scans of the vessels in the posterior pole of the
      eye may assist the clinical assessment of gross abnormalities of ocular blood
      flow, e.g. in carotid artery stenosis.

PMID- 23552099
TI  - Refractory chronic cough, or the need to focus on the relationship between the
      larynx and the esophagus.
AB  - In this review we question the current way of handling tackle a problem of
      chronic cough, especially by the excessive number of patients who can not find
      complete relief from your cough by anatomical diagnosis of universal use. From
      the field of Otolaryngology new perspectives arise now considering the larynx as
      a preferential afferent stimuli cough reflex arc. Also the constitution
      laryngopharyngeal reflux gas and new approaches to non-acid reflux and the local
      action of pepsin in laryngeal deserving of a joint review, which can illuminate
      new ways to handle the problem of chronic refractory cough. We believe that the
      chronic cough syndrome hpersensitivity as more precise label for chronic cough,
      should place particular emphasis on laryngeal sensory neuropathy as cough and
      reflux the influence that may have on their maintenance, and thereby causes
      definitely wide related to the syndrome if the larynx is incorporated, place
      greater number of afferent nerves of chronic cough, which are sure to cover much
      of the case of refractory cough remain without a satisfactory solution. The close
      collaboration between Otolaryngology, Gastroenterology and Pneumology in a
      patient with refractory chronic cough seems now an unavoidable necessity. 

PMID- 23552100
TI  - Organizational stressors, work-family interface and the role of gender in the
      hospital: experiences from Turkey.
AB  - OBJECTIVES: In the framework of the EU project 'Improving quality and safety in
      the hospital: The link between organizational culture, burnout and quality of
      care', focus groups (FGs) were conducted to explore hospital environment
      stressors and their relationship with health care professional (HP) well-being
      and quality of care. METHODS: Semi-structured interviews and FGs were used. Three
      mixed FGs with 23 health care workers, two FGs with 12 nurses, and another one
      with nine physicians were conducted. Thematic analyses were performed. Data were
      coded into main themes and subthemes. RESULTS: Three themes emerged from the
      discussions: (1) Organizational stressors associated with working conditions
      concerning the nature of the job, workload and working schedule, unclear role
      definition, lack of time for personal development, interpersonal relationships at
      work, changes in health policy, (2) work-family spillover and (3) the gendered
      nature of health care work and of patients' expectations, and the gendered
      character of the workplace. CONCLUSIONS: Health care professionals are faced with
      numerous challenges that create stress affecting their daily life. Job stressors
      related to working conditions, the negative and positive spillover of work-family
      interference and the gendered nature of health care work emerged as important
      issues for Turkish HPs. STATEMENT OF CONTRIBUTION: What is already known on this
      subject? In Turkey, gender has rarely been considered in the healthcare studies.
      Rapid changes in health reforms are making healthcare professionals more
      vulnerable to stress. The deteriation in the health system impacts women more
      than men, as higher ratios work in outsourced services. What does this study add?
      Despite signifcant changes in attitudes towards women, nurses are treated as
      "mothers" of the clinics. Women as health workers are particularly exposed to
      multiple stressors, that are rooted in ideals about gender. Understanding the way
      healthcare is organized along gendered lines is a precusor to any real
      organizational change.

PMID- 23552101
TI  - Cis-silencing of PIP5K1B evidenced in Friedreich's ataxia patient cells results
      in cytoskeleton anomalies.
AB  - Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease
      characterized by ataxia, variously associating heart disease, diabetes mellitus
      and/or glucose intolerance. It results from intronic expansion of GAA triplet
      repeats at the FXN locus. Homozygous expansions cause silencing of the FXN gene
      and subsequent decreased expression of the encoded mitochondrial frataxin.
      Detailed analyses in fibroblasts and neuronal tissues from FRDA patients have
      revealed profound cytoskeleton anomalies. So far, however, the molecular
      mechanism underlying these cytoskeleton defects remains unknown. We show here
      that gene silencing spreads in cis over the PIP5K1B gene in cells from FRDA
      patients (circulating lymphocytes and primary fibroblasts), correlating with
      expanded GAA repeat size. PIP5K1B encodes phosphatidylinositol 4-phosphate 5
      kinase beta type I (pip5k1beta), an enzyme functionally linked to actin
      cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate
      [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].
      Accordingly, loss of pip5k1beta function in FRDA cells was accompanied by
      decreased PI(4,5)P2 levels and was shown instrumental for destabilization of the
      actin network and delayed cell spreading. Knockdown of PIP5K1B in control
      fibroblasts using shRNA reproduced abnormal actin cytoskeleton remodeling,
      whereas over-expression of PIP5K1B, but not FXN, suppressed this phenotype in
      FRDA cells. In addition to provide new insights into the consequences of the FXN
      gene expansion, these findings raise the question whether PIP5K1B silencing may
      contribute to the variable manifestation of this complex disease. 

PMID- 23552102
TI  - Driver assistance system for passive multi-trailer vehicles with haptic steering
      limitations on the leading unit.
AB  - Driving vehicles with one or more passive trailers has difficulties in both
      forward and backward motion due to inter-unit collisions, jackknife, and lack of
      visibility. Consequently, advanced driver assistance systems (ADAS) for multi
      trailer combinations can be beneficial to accident avoidance as well as to driver
      comfort. The ADAS proposed in this paper aims to prevent unsafe steering commands
      by means of a haptic handwheel. Furthermore, when driving in reverse, the
      steering-wheel and pedals can be used as if the vehicle was driven from the back
      of the last trailer with visual aid from a rear-view camera. This solution, which
      can be implemented in drive-by-wire vehicles with hitch angle sensors, profits
      from two methods previously developed by the authors: safe steering by applying a
      curvature limitation to the leading unit, and a virtual tractor concept for
      backward motion that includes the complex case of set-point propagation through
      on-axle hitches. The paper addresses system requirements and provides
      implementation details to tele-operate two different off- and on-axle
      combinations of a tracked mobile robot pulling and pushing two dissimilar
      trailers.

PMID- 23552103
TI  - A high precision feature based on LBP and Gabor theory for face recognition.
AB  - How to describe an image accurately with the most useful information but at the
      same time the least useless information is a basic problem in the recognition
      field. In this paper, a novel and high precision feature called BG2D2LRP is
      proposed, accompanied with a corresponding face recognition system. The feature
      contains both static texture differences and dynamic contour trends. It is based
      on Gabor and LBP theory, operated by various kinds of transformations such as
      block, second derivative, direct orientation, layer and finally fusion in a
      particular way. Seven well-known face databases such as FRGC, AR, FERET and so on
      are used to evaluate the veracity and robustness of the proposed feature. A
      maximum improvement of 29.41% is achieved comparing with other methods. Besides,
      the ROC curve provides a satisfactory figure. Those experimental results strongly
      demonstrate the feasibility and superiority of the new feature and method.

PMID- 23552104
TI  - Estimating zenith tropospheric delays from BeiDou navigation satellite system
      observations.
AB  - The GNSS derived Zenith Tropospheric Delay (ZTD) plays today a very critical role
      in meteorological study and weather forecasts, as ZTDs of thousands of GNSS
      stations are operationally assimilated into numerical weather prediction models.
      Recently, the Chinese BeiDou Navigation Satellite System (BDS) was officially
      announced to provide operational services around China and its neighborhood and
      it was demonstrated to be very promising for precise navigation and positioning.
      In this contribution, we concentrate on estimating ZTD using BDS observations to
      assess its capacity for troposphere remote sensing. A local network which is
      about 250 km from Beijing and comprised of six stations equipped with GPS- and
      BDS-capable receivers is utilized. Data from 5 to 8 November 2012 collected on
      the network is processed in network mode using precise orbits and in Precise
      Point Positioning mode using precise orbits and clocks. The precise orbits and
      clocks are generated from a tracking network with most of the stations in China
      and several stations around the world. The derived ZTDs are compared with that
      estimated from GPS data using the final products of the International GNSS
      Service (IGS). The comparison shows that the bias and the standard deviation of
      the ZTD differences are about 2 mm and 5 mm, respectively, which are very close
      to the differences of GPS ZTD estimated using different software packages.

PMID- 23552105
TI  - Quantification of in vivo implant wear in total knee replacement from dynamic
      single plane radiography.
AB  - An in vivo method to measure wear in total knee replacements was developed using
      dynamic single-plane fluoroscopy. A dynamic, anthropomorphic total knee
      replacement phantom with interchangeable, custom-fabricated components of known
      wear volume was created, and dynamic imaging was performed. For each frame of the
      fluoroscopy data, the relative location of the femoral and tibial components were
      determined, and the apparent intersection of the femoral component with the
      tibial insert was used to calculate wear volume, wear depth, and frequency of
      intersection. No difference was found between the measured and true wear volumes.
      The precision of the measurements was +/-39.7 mm(3) for volume and +/-0.126 mm
      for wear depth. The results suggest the system is capable of tracking wear volume
      changes across multiple time points in patients. As a dynamic technique, this
      method can provide both kinematic and wear measurements that may be useful for
      evaluating new implant designs for total knee replacements.

PMID- 23552106
TI  - Interleukin 11 expression in the normal canine eye.
AB  - OBJECTIVES: The purpose of this study was to characterize the expression of
      interleukin-11 (IL-11), a cytokine with anti-inflammatory, cytoprotective, and
      immune-modulating characteristics, in the canine eye. PROCEDURES: Normal canine
      eyes were collected from clinically healthy dogs that had been euthanized for
      reasons unrelated to this study. The distribution of IL-11 expression in the
      different ocular layers was evaluated by immunofluorescence (eight eyes).
      Expression levels were quantified (based on fluorescence intensity) using pixel
      density analysis. Primary cell cultures were derived from all three corneal cell
      layers. IL-11 mRNA expression was assessed in these cultures using quantitative
      RT-PCR before and after treatment with TGF-beta1, a known inducer of IL-11
      expression. IL-11 protein expression was also assessed in the media of these
      cells by Western blot analysis. RESULTS: IL-11 protein was detected in the
      corneal epithelium, keratocytes, and the corneal endothelium of the normal canine
      eyes examined using immunofluorescence. Baseline IL-11 mRNA expression was noted
      in the corneal epithelium, fibroblasts, and endothelium using quantitative RT
      PCR. Treatment of canine corneal cell lines with TGF-beta1 resulted in
      statistically significant increases in IL-11 expression in the corneal
      epithelium, endothelial and fibroblast cell lines with strongest induction noted
      in the fibroblasts and endothelium. CONCLUSION: This is the first description of
      IL-11 expression in the canine eye. The protein and mRNA appear to be
      constitutively present throughout all layers of the cornea and are increased by
      TGF-beta1, a cytokine important in ocular inflammation and disease.

PMID- 23552107
TI  - A first-principles study on the intrinsic asymmetric ferroelectricity of the
      SrTiO3-BaTiO3-CaTiO3 tricolor superlattice at the nanoscale.
AB  - We report a systematic theoretical study on the ferroelectric behavior of
      ultrathin three-component ferroelectric films, e.g., CaTiO3-BaTiO3-SrTiO3,
      sandwiched between electrodes. Using first-principles calculations we demonstrate
      that such structures have intrinsic asymmetric ferroelectricity which is robust
      even at the nanoscale. In addition, there exists a certain relationship between
      the polarization directions and geometric stacking sequences of the
      superlattices. Specifically, the lowest energy states always have polarizations
      pointing from CaTiO3 via BaTiO3 to SrTiO3, while the sequence in the metastable
      states is SrTiO3-BaTiO3-CaTiO3. Therefore we were able to distinguish one
      ferroelectric state from its opposite state by means of their geometric stackings
      along the polarization directions. Besides this, band alignment analysis reveals
      that such structures are well behaved at the metal/ferroelectric interface,
      confirming the credibility and reliability of our first-principles calculation.
      Our finding may suggest a controllable and unambiguous way to build ferroelectric
      and multiferroic tunnel junctions.

PMID- 23552108
TI  - Burnout among therapists working with persons with autism after the 2009
      earthquake in L'Aquila, Italy: a longitudinal comparative study.
AB  - The aim of this study was to follow up the occurrence of burnout in therapists of
      children and adolescents with autism experiencing the 2009 earthquake in
      L'Aquila, and to discuss implications for burnout prevention after disasters. A
      longitudinal study was carried out, measuring burnout outcomes according to the
      Maslach Burnout Inventory in 11 exposed and 53 unexposed therapists. Staff in the
      exposed group appeared to report significantly higher levels of emotional
      exhaustion after 1 and 2 years of follow-up than the unexposed staff. As to lack
      of personal accomplishment, the exposed groups shows increasingly lower scores
      with respect to the unexposed group, with personal accomplishment (PA) values
      falling from 41.0 [standard deviation (SD) 3.7] to 33.4 (SD 4.1) after 2 years,
      whereas PA values remain stable over time in the unexposed group. As to
      depersonalization, data show no significant difference between groups. Burnout
      occurrence is induced by the exceptional stressors related with natural disasters
      like earthquakes. Efforts are required to help mental health workers, including
      psychiatric nurses, to cope with the devastating situation determined by an
      earthquake. A periodical monitoring of mental health status is recommended in
      mental health works, especially with regard to help with post-traumatic stress
      disorder, coping with work and therapeutic relationships, family and social life
      and economic impact.

PMID- 23552110
TI  - Graphene in the heart of Europe.

PMID- 23552109
TI  - Potential of entomopathogenic nematodes for the control of the banded fruit
      weevil, Phlyctinus callosus (Schonherr) (Coleoptera: Curculionidae).
AB  - Entomopathogenic nematodes (EPN) were evaluated for their potential use as
      biological control agents against Phlyctinus callosus, the banded fruit weevil
      (BFW). The susceptibility of larvae and adults to EPN was evaluated using 400
      infective juveniles (IJ) per insect after 4 days in 24-well bioassay trays. The
      nematode isolates used were all able to infect BFW, although the larvae were
      found to be more susceptible than were the adults. The percentage mortality for
      BFW larvae ranged from 41 to 73% and for BFW adults from 13 to 45%. The most
      effective isolate, SF41 of Heterorhabditis zealandica, was used to investigate
      the effect of vertical movement of nematodes in sand and sandy loam soil, at
      specified concentration and temperature. A higher (82.2 +/- 0.084%) percentage
      mortality rate was obtained with the sandy loam soil, than with the use of sand
      (67.5 +/- 0.12%). The LD50 and LD90 values after 4 days of incubation were 96 and
      278 IJ/50 MUl, respectively. Nematodes were inactive below 15  degrees C, with
      the highest mortality of 74 +/- 0.081% for BFW larvae recorded at 25  degrees C.
      Heterorhabditis zealandica was able to complete its life cycle successfully in
      sixth-instar BFW larvae after a period of 22 days. The study showed BFW larvae
      not to be as susceptible to nematode infection as they need a high concentration
      (400 IJ/larva) and 4 days to give effective control.

PMID- 23552111
TI  - The insurability of nanomaterial production risk.

PMID- 23552112
TI  - The three sisters of risk.

PMID- 23552114
TI  - Plasmonics: Harvest season for hot electrons.

PMID- 23552115
TI  - Spintronics: Getting current pulses under control.

PMID- 23552116
TI  - Quantum information: Atoms and circuits unite in silicon.

PMID- 23552117
TI  - Raman spectroscopy as a versatile tool for studying the properties of graphene.
AB  - Raman spectroscopy is an integral part of graphene research. It is used to
      determine the number and orientation of layers, the quality and types of edge,
      and the effects of perturbations, such as electric and magnetic fields, strain,
      doping, disorder and functional groups. This, in turn, provides insight into all
      sp(2)-bonded carbon allotropes, because graphene is their fundamental building
      block. Here we review the state of the art, future directions and open questions
      in Raman spectroscopy of graphene. We describe essential physical processes whose
      importance has only recently been recognized, such as the various types of
      resonance at play, and the role of quantum interference. We update all basic
      concepts and notations, and propose a terminology that is able to describe any
      result in literature. We finally highlight the potential of Raman spectroscopy
      for layered materials other than graphene.

PMID- 23552118
TI  - Copper-beta-amyloid peptides exhibit neither monooxygenase nor superoxide
      dismutase activities.
AB  - Contrary to earlier claims, the Cu(II) complex with the soluble Abeta16 peptide,
      and also that with Abeta28 exhibit no phenol monooxygenase (tyrosinase-like)
      activity; the complexes neither exhibit superoxide dismutase activity.

PMID- 23552119
TI  - Forster resonance energy transfer studies of calmodulin produced by native
      protein ligation reveal inter-domain electrostatic repulsion.
AB  - This study explores the influence of long-range intra-protein electrostatic
      interactions on the conformation of calmodulin in solution. Ensemble Forster
      resonance energy transfer (FRET) is measured for calmodulin with a fluorophore
      pair incorporated specifically with a donor at residue 17 and an acceptor at
      position 117. This construct was generated by a combination of solid phase
      peptide synthesis, cloning, expression and native chemical ligation. This
      labelling method has not previously been used with calmodulin and represents a
      convenient method for ensuring the explicit positioning of the fluorophores. The
      ensemble FRET experiments reveal significant electrostatic repulsion between the
      globular domains in the calcium-free protein. At low salt, calmodulin has a
      relatively extended conformation and the distance between the domains is further
      increased by denaturation, by heat or by non-ionic denaturants. The repulsion
      between domains is screened by salt and is also diminished by calcium binding,
      which changes the protein net charge from -23 to -15. Compared with the calcium
      free form at low salt, the FRET efficiency for the calcium-bound form has, on
      average, increased 10-fold. The conformation of the calcium form is insensitive
      to salt screening. These results imply that when the two globular domains of
      calmodulin interact with target, there is no significant free energy penalty due
      to electrostatic interactions.

PMID- 23552120
TI  - Spironolactone improves endothelial and cardiac autonomic function in non heart
      failure hemodialysis patients.
AB  - OBJECTIVES: Hemodialysis patients have a cardiovascular mortality rate of 20-40
      times that of the general population. Aldosterone inhibition by spironolactone
      has exerted beneficial, prognostically significant cardiovascular effects in
      patients with heart failure maintained on hemodialysis or peritoneal dialysis.
      Our aim was to investigate spironolactone's effect in non heart failure
      hemodialysis patients. METHODS: Fourteen stable chronic hemodialysis patients
      (nine men), 59.5 +/- 3.1 years of age were evaluated in a sequential, fixed-dose,
      placebo-controlled study. Heart failure was diagnosed on the basis of signs and
      symptoms of heart failure or left ventricular ejection fraction less than 50%.
      Following an initial 4-month period of placebo administration after each
      dialysis, patients received spironolactone (25 mg thrice weekly after dialysis)
      for the next 4 months. Data were recorded at baseline, at the end of placebo
      administration, and at the end of spironolactone treatment and included
      endothelial function by forearm reactive hyperemia during venous occlusion
      plethysmography, cardiac autonomic status by heart rate variability in the time
      and frequency domain, blood pressure response, and echocardiographic and
      laboratory data. RESULTS: Placebo induced no changes in the aforementioned
      parameters. Following spironolactone, salutary effects were observed in the
      extent and duration of reactive hyperemia (P < 0.05 for both), as well as in
      heart rate variability (P < 0.05) and blood pressure control (P < 0.05). No
      changes occurred in echocardiographically derived left ventricular dimensions or
      mass. CONCLUSION: Low-dose spironolactone therapy in clinically stable non heart
      failure hemodialysis patients is associated with favorable effects on
      cardiovascular parameters known to adversely affect survival, such as endothelial
      dysfunction and heart rate variability. Spironolactone treatment might benefit
      long-term cardiovascular outcome of such patients.

PMID- 23552121
TI  - L-Homoarginine and L-arginine are antagonistically related to blood pressure in
      an elderly population: the Hoorn study.
AB  - OBJECTIVES: Production of nitric oxide by the vascular endothelium is crucial for
      the maintenance of vascular tone, an important determinant of blood pressure. L
      Arginine and its homolog L-homoarginine are competitive substrates of nitric
      oxide synthase (NOS), whereas asymmetric dimethylarginine (ADMA) is a NOS
      inhibitor. We evaluated the relationships between physiological levels of these
      amino acids and blood pressure. METHODS: The relationship between blood pressure
      and plasma levels of L-arginine, L-homoarginine, and ADMA was studied in
      participants of the Hoorn study, a population-based cohort study of elderly
      participants (n = 746, aged 50-87, 49.5% men). RESULTS: In linear regression
      models adjusted for age, sex, L-arginine, and ADMA, a positive association was
      observed between L-homoarginine and SBP [3.90 mmHg per 1-SD increment of L
      homoarginine (95% confidence interval, CI 2.28-5.52)] and DBP [1.83 (0.95-2.72)].
      In these models, L-arginine was not significantly associated with SBP [-0.68 mmHg
      per 1-SD increment of L-arginine (95% CI -2.23 to 0.88)], but a significant
      inverse association with DBP was observed [-1.17 (-2.02 to -0.32)]. These
      associations were slightly attenuated after further adjustment for glucose or
      BMI, but not after adjustment for other cardiovascular risk factors (lipids,
      smoking, inflammation markers, microalbuminuria, prior cardiovascular disease,
      and antihypertensive medication). ADMA was not significantly associated with
      either SBP or DBP. CONCLUSION: In elderly participants, plasma levels of L
      homoarginine and L-arginine are independently associated with clinically relevant
      differences in blood pressure in an antagonistic fashion.

PMID- 23552122
TI  - Dietary iron restriction prevents further deterioration of renal damage in a
      chronic kidney disease rat model.
AB  - OBJECTIVE: Iron accumulation is associated with the pathogenesis of chronic
      kidney disease (CKD). However, little is known about the effects of isolated iron
      restriction against CKD. We have recently reported that iron restriction prevents
      the development of renal damage in the well established 5/6 nephrectomy rat model
      of CKD. Herein, we investigated the therapeutic effects of iron restriction on
      preexisting hypertension and renal damage in a rat model of CKD. METHODS: CKD was
      induced by 5/6 nephrectomy in Sprague-Dawley rats. After surgery, 5/6
      nephrectomized rats were given an iron-restricted diet from 1 day to 16 weeks for
      prevention protocol or from 8 to 16 weeks for rescue protocol. Other CKD rats
      were given a normal diet. RESULTS: At 16 weeks after surgery, CKD rats developed
      hypertension and renal damage. Early intervention with iron restriction prevented
      the development of hypertension and vascular remodeling. By contrast, late
      intervention with iron restriction did not remarkably ameliorate preexisting
      hypertension and vascular remodeling in CKD rats. On the contrary, late
      intervention with iron restriction prevented further progression of preexisting
      renal damage in CKD rats. Interestingly, iron restriction led to increased
      urinary sodium and decreased urinary potassium excretions in CKD rats. Moreover,
      iron restriction markedly attenuated renal expression of nuclear
      mineralocorticoid receptor and Rac1 activity in CKD rats. CONCLUSION: Iron
      restriction prevented further deterioration of preexisting renal damage. The
      beneficial effects of iron restriction on renal damage seem to be associated with
      inhibition of renal mineralocorticoid receptor signaling.

PMID- 23552123
TI  - Contribution of Rho kinase to blood pressure elevation and vasoconstrictor
      responsiveness in type 2 diabetic Goto-Kakizaki rats.
AB  - OBJECTIVES: The RhoA-Rho kinase (ROCK) pathway contributes to a number of
      diabetic complications including cardiomyopathy and nephropathy. In this study,
      we investigated whether it contributes to elevated blood pressure and vascular
      contractile dysfunction in type 2 diabetes. METHODS: Blood pressure was measured
      in Goto-Kakizaki rats, a nonobese model of type 2 diabetes, before and after
      treatment with the ROCK inhibitor fasudil. Vasoconstrictor responsiveness in the
      absence and presence of ROCK inhibitors as well as ROCK pathway activity was
      measured in isolated mesenteric resistance vessels from these animals. RESULTS:
      Blood pressure was elevated in diabetic rats compared with age-matched Wistar
      controls, and was normalized by treatment with fasudil. Contractile responses of
      mesenteric arteries from diabetic rats to phenylephrine and U-46619, as well as
      relaxant responses to acetylcholine, were unaltered. However, vasoconstrictor
      responses were more sensitive to ROCK inhibition with either Y-27632 or H-1152
      than were responses of control arteries. No differences were found in expression
      of RhoA, ROCK1, or ROCK2 or in basal ROCK activity between arteries from control
      and diabetic rats. U-46619 produced a similar magnitude of increase in ROCK
      activity that was completely blocked by H-1152 in arteries from both groups of
      animals. CONCLUSION: These data suggest that ROCK contributes to the increase in
      blood pressure in type 2 diabetic Goto-Kakizaki rats, and that vasoconstrictor
      responses of small mesenteric arteries from these animals are more dependent on
      ROCK than are responses of control arteries.

PMID- 23552124
TI  - Antihypertensive classes, cognitive decline and incidence of dementia: a network
      meta-analysis.
AB  - OBJECTIVES: Prevention of cognitive decline and dementia with blood pressure
      lowering treatments has shown inconsistent results. We compared the effects of
      different classes of antihypertensive drugs on the incidence of dementia, and on
      cognitive function. METHODS: We conducted a systematic review and included 19
      randomized trials (18 515 individuals) and 11 studies (831 674 individuals)
      analysing the effects of antihypertensive treatment on cognition and on the
      incidence of dementia, respectively, in hypertensive patients without prior
      cerebrovascular disorders. Network meta-analysis was used for the comparison of
      antihypertensive classes. RESULTS: Antihypertensive treatment, regardless of the
      drug class, had benefits on overall cognition [effect size 0.05, 95% confidence
      interval (CI) 0.02-0.07] and all cognitive functions except language.
      Antihypertensive treatment reduced the risk of all-cause dementia by 9%, with
      reference to the control group (hazard ratio 0.91, 95% CI 0.89-0.94), when
      randomized trials and observationnal studies were combined (n = 15). Result was
      not significant with randomized trials alone (n = 4). Angiotensin II receptor
      blockers (ARBs) had larger benefits than placebo on overall cognition (adjusted
      effect size 0.60 +/- 0.18, P = 0.02). ARBs were more effective than beta-blockers
      (0.67 +/- 0.18, P = 0.01), diuretics (0.54 +/- 0.19, P = 0.04) and angiotensin
      converting enzyme inhibitors (0.47 +/- 0.17, P = 0.04) in rank. The mean change
      in blood pressure did not differ significantly between the different
      antihypertensive drug classes. CONCLUSION: Our results support the notion that
      antihypertensive treatment has beneficial effects on cognitive decline and
      prevention of dementia, and indicate that these effects may differ between drug
      classes with ARBs possibly being the most effective.

PMID- 23552125
TI  - Absolute height-specific thresholds to identify elevated blood pressure in
      children.
AB  - OBJECTIVE: Identification of children with elevated blood pressure (BP) is
      difficult because of the multiple sex, age, and height-specific thresholds to
      define elevated BP. We propose a simple set of absolute height-specific BP
      thresholds and evaluate their performance to identify children with elevated BP
      in two different populations. METHODS: Using the 95th sex, age, and relative
      height BP US thresholds to define elevated BP in children (standard criteria), we
      derived a set of (non sex- and non age-specific) absolute height-specific BP
      thresholds for 11 height categories by 10 cm increments. Using data from large
      school-based surveys conducted in Switzerland (N = 5207; 2621 boys, 2586 girls;
      age range: 10.1-14.9 years) and in the Seychelles (N = 25 759; 13 048 boys, 12
      711 girls; age range: 4.4-18.8 years), we evaluated the performance of these
      height-specific thresholds to identify children with elevated BP. We also derived
      sex-specific absolute height-specific BP thresholds and compared their
      performance. RESULTS: In the Swiss and the Seychelles surveys, the prevalence of
      elevated BP (standard criteria) was 11.4 and 9.1%, respectively. The height
      specific thresholds to identify elevated BP had a sensitivity of 80 and 84%, a
      specificity of 99 and 99%, a positive predictive value of 92 and 91%, and a
      negative predictive value of 97 and 98%, respectively. Performance of sex
      specific absolute height-specific BP thresholds was similar. CONCLUSION: A simple
      table of height-specific BP thresholds allowed identifying children with elevated
      BP with high sensitivity and excellent specificity.

PMID- 23552126
TI  - Muscle and skin sympathetic nerve traffic during physician and nurse blood
      pressure measurement.
AB  - OBJECTIVE: Previous studies have shown that blood pressure assessment by a nurse
      markedly attenuates the pressor and tachicardic responses triggered by the
      physician blood pressure measurement. Whether and to what extent this attenuation
      reflects a different pattern of the neuroadrenergic responses to doctor or nurse
      blood pressure evaluation is unknown. METHODS: In 19 lean untreated mild
      essential hypertensive patients (age 39.1 +/- 2.4 years, mean +/- SEM), we
      measured beat-to-beat mean arterial pressure (Finapres), heart rate (ECG), and
      efferent postganglionic muscle and skin sympathetic nerve traffic [muscle
      sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA),
      respectively, by microneurography], before, during, and following a 10-min
      sphygmomanometric BP measurement by a doctor or by a nurse unfamiliar to the
      patients. Measurements were repeated at a 30-min interval to obtain, in separate
      periods, muscle and skin sympathetic nerve traffic recordings. Both the sequences
      (doctor vs. nurse and muscle vs. skin sympathetic nerve traffic) were randomized.
      RESULTS: A doctor visit induced sudden, marked, and prolonged blood pressure and
      heart rate increases, accompanied by a muscle sympathetic nerve traffic
      inhibition (average response: -18.1 +/- 4.3%, P < 0.01) coupled with a skin
      sympathetic nerve traffic excitation (average response: +46.1 +/- 5.5%, P <
      0.01). In contrast, a nurse visit elicited blood pressure and heart rate
      responses markedly and significantly reduced (-72.1 +/- 11 and -81.7 +/- 13%
      respectively, P < 0.01) as compared with those seen during the doctor's visit.
      This was the case also for muscle and skin sympathetic neural responses (-44.3 +/
      9 and -65.6 +/- 13%, P < 0.01). CONCLUSION: These data provide the first
      evidence that the blunted pressor and tachicardic responses to nurse's blood
      pressure measurements are accompanied by an attenuation of the adrenergic neural
      responses seen during the alerting reaction accompanying doctor's blood pressure
      measurement.

PMID- 23552128
TI  - Pressure points in primary care: blood pressure and management of hypertension in
      532 050 patients from 2005 to 2010.
AB  - BACKGROUND: Hypertension results in high morbidity and mortality. Its management
      is predominantly undertaken in the primary care setting. The aim of this study
      was to assess trends in blood pressure (BP) and hypertensive management in
      primary care in Australia. METHODS: A retrospective analysis of patient-based
      electronic medical records was conducted. Antihypertensive therapy was determined
      by prescription data. We identified 532 050 patients (55% women, average age 54
      +/- 18 years) being managed by 733 general practitioners from 286 clinics
      Australia-wide who had at least one visit with BP recorded between 2005 and 2010.
      RESULTS: Average BP did not change and men had consistently higher levels than
      women (132/79 vs. 127/77 mmHg, P < 0.001). At least 25% of all individuals had a
      visit where elevated BP more than 140/90 mmHg was recorded. Up to 50% of patients
      on antihypertensive therapy had a BP more than 140/90 mmHg. In any year, the odds
      of elevated BP more than 140/90 mmHg were three-fold to four-fold higher in
      treated individuals (yearly range OR 3.0-3.97; 95% CI 2.93-3.83 to 3.08-4.10).
      Over annual contiguous visits in 51 721 patients with BP more than 140/90 mmHg,
      BP decreased after two visits and then remained stable (P < 0.001) irrespective
      of frequency of visits or antihypertensive treatment. Individuals with more
      frequent visits were more likely to attain target BP less than 140/90 mmHg [OR
      1.08 (three visits) to 1.29 (five visits); 95% CI range 1.03-1.38]. CONCLUSION:
      In the absence of any significant gains in the community control of hypertension
      since 2005, a more intensive approach to BP management in primary care is
      required to ensure more patients achieve BP targets.

PMID- 23552129
TI  - Aortic, but not brachial blood pressure category enhances the ability to identify
      target organ changes in normotensives.
AB  - AIMS: We sought to determine whether within normal/high-normal blood pressure
      (BP) ranges (120-139/80-89 mmHg), aortic BP may further refine BP-related
      cardiovascular risk assessment, as determined from target organ changes. METHODS:
      In 1169 participants from a community sample of African ancestry, 319 (27%) of
      whom had a normal/high-normal BP, aortic BP was determined using radial
      applanation tonometry and SphygmoCor software, and target organ changes assessed
      from carotid-femoral pulse wave velocity (PWV) (n = 1025), estimated glomerular
      filtration rate (eGFR) (n = 944), and left ventricular mass indexed to height
      (LVMI) (n = 690). RESULTS: Normal versus high-normal BP categories failed to
      differentiate between those participants with a BP above optimal values with
      versus without multivariate-adjusted target organ changes. However, in those with
      a normal/high-normal BP with aortic SBP values that were less than 95% confidence
      interval of healthy participants with optimal BP values (45% of those with a
      normal/high-normal BP), no unadjusted or multivariate adjusted target organ
      changes were noted. In contrast, those with a normal/high-normal BP with aortic
      SBP values that exceeded optimal thresholds, demonstrated unadjusted and
      multivariate adjusted increases in PWV and LVMI and decreases in eGFR (P < 0.05
      to P < 0.005 after multivariate adjustments). CONCLUSION: In contrast to normal
      versus high-normal BP categories which do not clearly distinguish normotensives
      with from those without organ damage, noninvasively determined aortic BP
      measurements may refine the ability to detect those with a normal/high-normal BP
      at risk of BP-related cardiovascular damage.

PMID- 23552127
TI  - Zofenopril and ramipril and acetylsalicylic acid in postmyocardial infarction
      patients with left ventricular systolic dysfunction: a retrospective analysis in
      hypertensive patients of the SMILE-4 study.
AB  - BACKGROUND: Antecedent hypertension represents a risk factor for adverse outcomes
      in survivors of acute myocardial infarction (AMI). Prognosis of such patients
      might be greatly improved by drugs enhancing blood pressure control. In the
      present retrospective analysis of the randomized, double-blind, parallel-group,
      SMILE-4 study we compared the efficacy of zofenopril 60 mg and acetylsalicylic
      acid (ASA) 100 mg versus ramipril 10 mg and ASA in patients with AMI complicated
      by left ventricular dysfunction, classified according to a history of
      hypertension. METHODS: The primary study end-point was 1-year combined occurrence
      of death or hospitalization for cardiovascular causes. Hypertension was defined
      according to medical history and current blood pressure values at entry and could
      be determined in 682 of 716 patients of the intention-to-treat analysis. RESULTS:
      One hundred and fifty-seven patients (23%) were normotensives and 525 (77%)
      hypertensives. In the normotensive population the primary end-point occurred in
      19 of 76 zofenopril-treated patients (25%) and in 23 of 81 ramipril-treated
      patients (28%) [odds ratio (95% confidence interval): 0.84 (0.41-1.71), P =
      0.631]. In the hypertensive population, major cardiovascular outcomes were
      reported in 84 of 273 zofenopril-treated patients (31%) and in 99 of 252 ramipril
      treated patients (39%), with a 31% significantly (P = 0.041) lower risk with
      zofenopril [0.69 (0.48-0.99)]. The superiority of zofenopril versus ramipril was
      particularly evident in patients with isolated systolic hypertension [n = 131,
      0.48 (0.23-0.99), P = 0.045]. CONCLUSION: This retrospective analysis of the
      SMILE-4 study confirmed the good efficacy of zofenopril and ASA in the prevention
      of long-term cardiovascular outcomes also in the subgroup of patients with
      hypertension.

PMID- 23552130
TI  - Interleukin-4 deficiency induces mild preeclampsia in mice.
AB  - OBJECTIVE: Inflammation is necessary for successful pregnancy; however, excessive
      inflammation plays a central role in the development of the pregnancy-specific
      hypertensive disorder preeclampsia. Numerous anti-inflammatory cytokines are
      decreased in women with preeclampsia but the role of individual cytokines in
      blood pressure regulation during pregnancy is unknown. Therefore, we examined
      whether the lack of the potent anti-inflammatory cytokine interleukin-4 (IL-4)
      would be sufficient to elicit a preeclampsia-like syndrome in mice, and when
      coupled with immune system activation that these symptoms would be further
      augmented. METHODS: Measures of splenic immune cells, placental inflammation,
      blood pressure, endothelial function, and urinary protein excretion were
      performed in pregnant IL-4-deficient mice as well as in pregnant IL-4-deficient
      mice treated with the Toll-like receptor 3 agonist polyinosinic:polycytidylic
      (poly I:C). RESULTS: Pregnant IL-4-deficient mice exhibited altered splenic
      immune cell subsets, increased levels of pro-inflammatory cytokines, placental
      inflammation, mild hypertension, endothelial dysfunction, and proteinuria
      compared to pregnant control mice. Compared to pregnant control mice treated with
      poly I:C which exhibit preeclampsia-like symptoms, poly I:C-treated pregnant IL-4
      deficient mice exhibited a further increase in pro-inflammatory cytokine levels,
      which was associated with augmented SBP and endothelial dysfunction. CONCLUSION:
      Collectively, these data show that the absence of IL-4 is sufficient to induce
      mild preeclampsia-like symptoms in mice due to excessive inflammation. Thus, the
      anti-inflammatory effects of IL-4 are important in preventing hypertension during
      pregnancy.

PMID- 23552131
TI  - Cost-effectiveness analysis of cardiac resynchronization therapy in patients with
      NYHA I and NYHA II heart failure in Spain.
AB  - OBJECTIVES: The aim of the study was to combine clinical results from the
      European Cohort of the REVERSE study and costs associated with the addition of
      cardiac resynchronization therapy (CRT) to optimal medical therapy (OMT) in
      patients with mild symptomatic (NYHA I-II) or asymptomatic left ventricular
      dysfunction and markers of cardiac dyssynchrony in Spain. METHODS: A Markov model
      was developed with CRT + OMT (CRT-ON) versus OMT only (CRT-OFF) based on a
      retrospective cost-effectiveness analysis. Raw data was derived from literature
      and expert opinion, reflecting clinical and economic consequences of patient's
      management in Spain. Time horizon was 10 years. Both costs (euro 2010) and
      effects were discounted at 3 percent per annum. RESULTS: CRT-ON showed higher
      total costs than CRT-OFF; however, CRT reduced the length of hospitalization in
      ICU by 94 percent (0.006 versus 0.091 days) and general ward in by 34 percent
      (0.705 versus 1.076 days). Surviving CRT-ON patients (88.2 percent versus 77.5
      percent) remained in better functional class longer, and they achieved an
      improvement of 0.9 life years (LYGs) and 0.77 years quality-adjusted life years
      (QALYs). CRT-ON proved to be cost-effective after 6 years, except for the 7th
      year due to battery depletion. At 10 years, the results were ?18,431 per LYG and
      ?21,500 per QALY gained. Probabilistic sensitivity analysis showed CRT-ON was
      cost-effective in 75.4 percent of the cases at 10 years. CONCLUSIONS: The use of
      CRT added to OMT represents an efficient use of resources in patients suffering
      from heart failure in NYHA functional classes I and II.

PMID- 23552132
TI  - Effects of convergent diffusion and charge transfer kinetics on the diffusion
      layer thickness of spherical micro- and nanoelectrodes.
AB  - Nuances of the linear diffusion layer approximation are examined for slow charge
      transfer reactions at (hemi)spherical micro- and nanoelectrodes. This
      approximation is widely employed in Electrochemistry to evaluate the extent of
      electrolyte solution perturbed by the electrode process, which is essential to
      the understanding of the effects arising from thin-layer diffusion, convergent
      diffusion, convection, coupled chemical reactions and the double layer. The
      concept was well established for fast charge transfer processes at
      macroelectrodes, but remains unclear under other conditions such that a thorough
      assessment of its meaning was necessary. In a previous publication [A. Molina, J.
      Gonzalez, E. Laborda and R. G. Compton, Phys. Chem. Chem. Phys., 2013, 15, 2381
      2388] we shed some light on the influence of the reversibility degree. In the
      present work, the meaning of the diffusion layer thickness is investigated when
      very small electrodes are employed and so the contribution of convergent
      diffusion to the mass transport is very important. An analytical expression is
      given to calculate the linear diffusion layer thickness at (hemi)spherical
      electrodes and its behaviour is studied for a wide range of conditions of
      reversibility (from reversible to fully-irreversible processes) and electrode
      size (from macro- to nano-electrodes). Rigorous analytical solutions are deduced
      for true concentration profiles, surface concentrations, linear diffusion layer
      thickness and current densities when a potential pulse is applied at
      (hemi)spherical electrodes. The expressions for the magnitudes mentioned above
      are valid for electrodes of any size (including (hemi)spherical nanoelectrodes)
      and for any degree of reversibility, provided that mass transport occurs
      exclusively via diffusion. The variation of the above with the electrode size,
      applied potential and charge transfer kinetics is studied.

PMID- 23552134
TI  - [Does abortion lead to adverse effects?].

PMID- 23552133
TI  - Message, message, message.

PMID- 23552135
TI  - [The largest, the smallest and most complex].

PMID- 23552136
TI  - [Minister Store and hospital policy].

PMID- 23552137
TI  - [Sperm mutations and older fathers].

PMID- 23552138
TI  - [Iron levels and plasma sTfR].

PMID- 23552139
TI  - [Investigation of anemia].

PMID- 23552140
TI  - [T.-A. Hagve and colleagues reply].

PMID- 23552141
TI  - [Neurography not always necessary].

PMID- 23552143
TI  - [Unreliable observational studies].

PMID- 23552145
TI  - [Wrong about fat].

PMID- 23552146
TI  - [H. Storhaug replies].

PMID- 23552147
TI  - [Energy density is not insignificant].

PMID- 23552148
TI  - [Fat and dietary advice].

PMID- 23552149
TI  - [Tor Ole Klemsdal replies].

PMID- 23552152
TI  - [Pregabalin should be moved to the prescription group B].

PMID- 23552153
TI  - [Inconsistent research education].

PMID- 23552154
TI  - Organised mammographic screening--more benefits than harms.

PMID- 23552155
TI  - [Oral contraceptives, migraine and stroke].

PMID- 23552157
TI  - [Do previous abortions cause fear of childbirth?].
AB  - BACKGROUND: Abortion is a matter that concerns many women, and we have little
      knowledge about the effects of such experiences with regard to later pregnancies.
      The objective of the study was to investigate whether a previous history of
      abortion has an effect on later development of fear of childbirth, adjusted for
      the woman's mental health, parity, previous stillbirths and socio-demographic
      factors. MATERIAL AND METHODS: The study included 2,753 pregnant women from
      Akershus University Hospital. Information was collected with the aid of
      questionnaires in the 18th and 32nd week of gestation, as well as retrievals from
      the hospital's system of birth records. Fear of childbirth was measured on the
      Wijma scale (W-DEQ). RESULTS: The prevalence of fear of childbirth (defined as W
      DEQ >= 85) amounted to 11.7% among women who had undertaken two or more elective
      abortions and 7.8% among those who had no previous abortions. This trend was not
      statistically significant and disappeared completely in the adjusted analyses.
      Nor did we find any correlation between spontaneous abortions and fear of
      childbirth. The mental health of the woman was the one factor that was most
      strongly associated with fear of childbirth, an association that we have found
      also on a previous occasion in analyses of a smaller proportion of this cohort.
      INTERPRETATION: We found no co-variance between previous abortion history and
      fear of childbirth.

PMID- 23552158
TI  - [Acute internal hernia following gastric bypass for morbid obesity].
AB  - BACKGROUND: Approximately 3,000 bariatric operations are performed in Norway
      annually. Laparoscopic gastric bypass is the most widely used procedure. Internal
      hernia is a potentially serious cause of acute abdominal pain after a gastric
      bypass. MATERIAL AND METHOD: The review is based on a discretionary selection of
      articles found in PubMed coupled with the authors' personal clinical experience.
      RESULTS: Internal hernias due to protrusion of the bowel through mesenterial
      defects, or slits, occur in approximately 0-10% of patients after a gastric
      bypass. The incidence depends on follow-up time, surgical technique and whether
      the mesenterial slits were closed during the operation. The pain may be acute,
      intense and prolonged, with nausea and vomiting, or intermittent, following food
      intake. Cases of acute pain may be due to obstruction of and reduced blood
      circulation to the bowel, and require an emergency operation. A CT scan may
      reveal or arouse suspicion of an obstruction, but cannot rule it out. Pregnancy
      is a risk factor, and fertile women should be informed of this. Many recommend
      closure of mesenterial slits during the primary operation to reduce the risk of
      hernia. INTERPRETATION: Internal hernia after a gastric bypass is a potentially
      serious and not uncommon complication requiring rapid surgical intervention. All
      departments with preparedness for emergency abdominal surgery should be aware of
      this condition.

PMID- 23552159
TI  - [Double pylorus].

PMID- 23552160
TI  - [Young boy with fever, sore throat, sore lips and bullous rashes].

PMID- 23552161
TI  - Anal sphincter rupture during delivery: philosophy of science and clinical
      practice.

PMID- 23552162
TI  - Reclaim the profession!

PMID- 23552163
TI  - [Neurasthenia in Norway 1880-1920].
AB  - Neurasthenia was introduced as a diagnostic category in America in 1869, and
      rapidly spread to Europe. Many have drawn parallels between the historical
      disease entity of neurasthenia and contemporary conditions such as chronic
      fatigue syndrome/myalgic encephalopathy and burn-out, but we have little
      knowledge about the early history of neurasthenia in Norway. On the basis of
      Norwegian medical journals from the period 1880-1920, we have sought to study the
      introduction, understanding and application of the concept of neurasthenia in
      Norwegian medical practice, with particular emphasis on symptoms, causes,
      treatment, prognosis and prevalence. Results show that the term was probably used
      in a Norwegian medical journal for the first time in 1876, and during the 1880s
      there followed an increasing number of reports of people who had been diagnosed
      with neurasthenia. The condition was defined as a weakness of the nervous system.
      The symptom picture was extensive, with exhaustion as the main symptom. The
      causes of the symptoms could not be objectively verified or located, and theories
      abounded. Overexertion was a common explanation, although traumas, infections,
      malnutrition, heredity and sexual excesses were also assumed to be causes. The
      recommended treatment focused on strengthening the nervous system, for example
      through rest and electrotherapy. The condition was described as typical of its
      time, as a response to the "Zeitgeist" and modern life.

PMID- 23552164
TI  - [The best can make mistakes].

PMID- 23552165
TI  - [Seen from the hospital bed].

PMID- 23552166
TI  - [Densification].

PMID- 23552169
TI  - Marital satisfaction and depression among couples following men's acute coronary
      syndrome: testing dyadic dynamics in a longitudinal design.
AB  - OBJECTIVES: The current study examined the contribution of marital satisfaction
      to symptoms of depression among patients with acute coronary syndrome (ACS) and
      their partners. METHOD: The sample comprised of 91 ACS male patients and their
      female partners. Data were collected at the time of initial hospitalization and 6
      months later. Patients' and partners' assessments of marital satisfaction were
      measured using the ENRICH scale. Symptoms of depression were measured using the
      Brief Symptoms Inventory (BSI). Dyadic analysis applying the Actor-Partner Inter
      dependence Model (APIM) was used. RESULTS: Different patterns emerged for the two
      phases. In the acute phase, only the Actor effect was significant: for both
      patients and partners, one's greater marital satisfaction was associated with
      one's lower levels of depression. In the chronic phase, both Actor and Partner
      effects were significant, while different trends were found for patients and
      partners. Partners' marital satisfaction was associated with their own and the
      patients' decreased depression symptoms, whereas among patients, higher levels of
      marital satisfaction were associated with elevated levels of depression both for
      themselves and for their partners. CONCLUSIONS: A dyadic perspective and phases
      of illness have to be taken into account in understanding adjustment and
      developing interventions following ACS. STATEMENT OF CONTRIBUTION: What is
      already known on this subject? The contribution of marital satisfaction to
      psychological adjustment following cardiac illness has been explored, but mainly
      from the perspective of one partner only. Different phases of an illness present
      different challenges for both patients and family members. What does this study
      add? A dyadic perspective on recovery from cardiac illness. The partner's
      contribution during the different phases of the illness.

PMID- 23552170
TI  - Serum gamma-glutamyltransferase and uric acid levels are associated with impaired
      fasting glucose in adults from Inner Mongolia, China.
AB  - BACKGROUND: Serum gamma-glutamyltransferase (GGT) and uric acid (UA) levels are
      elevated in patients with diabetes or cardiovascular disease. Prediabetes,
      characterized by impaired glucose tolerance, is an important risk factor for
      overt diabetes as well as cardiovascular disease. Therefore, the aim of this
      study was to explore the relationship between GGT, UA and prediabetes in a
      Chinese population, and provide a scientific basis for the early prevention and
      treatment of diabetes. METHODS: We performed a cross-sectional population-based
      study in a cohort of 2694 subjects (1211 men and 1483 women, aged 35-86 years).
      Questionnaires and physical examinations were performed using standardized
      procedures. Fasting blood was collected to measure glucose and other biochemical
      parameters. The subjects were divided into two groups with either normal fasting
      glucose (NFG) or impaired fasting glucose (IFG), according to international
      diagnostic criteria. Logistic regression analysis was performed to estimate odds
      ratios (OR) and 95% confidence intervals. RESULTS: Compared with the NFG group,
      the IFG group had significantly higher blood pressure but lower high-density
      lipoprotein-cholesterol in women. Body mass index, waist circumference,
      triglyceride, glucose, GGT, and UA levels were significantly higher in males and
      females in the IFG group than those in the NFG group. Logistic regression
      analysis revealed that the OR for prediabetes increased with increasing serum GGT
      quartiles and UA quartiles. GGT and UA were positively associated with
      prediabetes in men and women, independent of age, ethnicity, smoking, alcohol
      consumption, blood pressure, physical labor, and other confounders. CONCLUSIONS:
      We found that serum GGT and UA levels were positively associated with prediabetes
      in men and women living in areas inhabited by Chinese ethnic minorities. As
      elevated GGT and UA levels were associated with significantly increased risk of
      prediabetes, they may be used as sensitive biological markers of prediabetes.

PMID- 23552171
TI  - Isolation and expression analysis of cDNAs that are associated with alternate
      bearing in Olea europaea L. cv. Ayvalik.
AB  - BACKGROUND: Olive cDNA libraries to isolate candidate genes that can help
      enlightening the molecular mechanism of periodicity and / or fruit production
      were constructed and analyzed. For this purpose, cDNA libraries from the leaves
      of trees in "on year" and in "off year" in July (when fruits start to appear) and
      in November (harvest time) were constructed. Randomly selected 100 positive
      clones from each library were analyzed with respect to sequence and size. A fruit
      flesh cDNA library was also constructed and characterized to confirm the
      reliability of each library's temporal and spatial properties. RESULTS:
      Quantitative real-time RT-PCR (qRT-PCR) analyses of the cDNA libraries confirmed
      cDNA molecules that are associated with different developmental stages (e. g. "on
      year" leaves in July, "off year" leaves in July, leaves in November) and fruits.
      Hence, a number of candidate cDNAs associated with "on year" and "off year" were
      isolated. Comparison of the detected cDNAs to the current EST database of GenBank
      along with other non - redundant databases of NCBI revealed homologs of
      previously described genes along with several unknown cDNAs. Of around 500
      screened cDNAs, 48 cDNA elements were obtained after eliminating ribosomal RNA
      sequences. These independent transcripts were analyzed using BLAST searches
      (cutoff E-value of 1.0E-5) against the KEGG and GenBank nucleotide databases and
      37 putative transcripts corresponding to known gene functions were annotated with
      gene names and Gene Ontology (GO) terms. Transcripts in the biological process
      were found to be related with metabolic process (27%), cellular process (23%),
      response to stimulus (17%), localization process (8.5%), multicellular organismal
      process (6.25%), developmental process (6.25%) and reproduction (4.2%).
      CONCLUSIONS: A putative P450 monooxigenase expressed fivefold more in the "on
      year" than that of "off year" leaves in July. Two putative dehydrins expressed
      significantly more in "on year" leaves than that of "off year" leaves in
      November. Homologs of UDP - glucose epimerase, acyl - CoA binding protein, triose
      phosphate isomerase and a putative nuclear core anchor protein were significant
      in fruits only, while a homolog of an embryo binding protein / small GTPase
      regulator was detected in "on year" leaves only. One of the two unknown cDNAs was
      specific to leaves in July while the other was detected in all of the libraries
      except fruits. KEGG pathway analyses for the obtained sequences correlated with
      essential metabolisms such as galactose metabolism, amino sugar and nucleotide
      sugar metabolisms and photosynthesis. Detailed analysis of the results presents
      candidate cDNAs that can be used to dissect further the genetic basis of fruit
      production and / or alternate bearing which causes significant economical loss
      for olive growers.

PMID- 23552172
TI  - Who steers the ship? Rural family physicians' views on collaborative care models
      for patients with dementia.
AB  - Little is known about the views of rural family physicians (FPs) regarding
      collaborative care models for patients with dementia. The study aims were to
      explore FPs' views regarding this issue, their role in providing dementia care,
      and the implications of providing dementia care in a rural setting. This study
      employed an exploratory qualitative design with a sample of 15 FPs. All rural FPs
      indicated acceptance of collaborative models. The main disadvantages of
      practicing rural were accessing urban-based health care and related services and
      a shortage of local health care resources. The primary benefit of practicing
      rural was FPs' social proximity to patients, families, and some health care
      workers. Rural FPs provided care for patients with dementia that took into
      account the emotional and practical needs of caregivers and families. FPs
      described positive and negative implications of rural dementia care, and all were
      receptive to models of care that included other health care professionals. 

PMID- 23552175
TI  - Predicting the risk of postoperative complications in obese patients: how close
      are we?

PMID- 23552174
TI  - Using Six Sigma methodology to reduce patient transfer times from floor to
      critical-care beds.
AB  - INTRODUCTION: In response to concerns regarding delays in transferring critically
      ill patients to intensive care units (ICU), a quality improvement project, using
      the Six Sigma process, was undertaken to correct issues leading to transfer
      delay. OBJECTIVE: To test the efficacy of a Six Sigma intervention to reduce
      transfer time and establish a patient transfer process that would effectively
      enhance communication between hospital caregivers and improve the continuum of
      care for patients. METHODS: The project was conducted at a 714-bed tertiary care
      hospital in Staten Island, New York. A Six Sigma multidisciplinary team was
      assembled to assess areas that needed improvement, manage the intervention, and
      analyze the results. RESULTS: The Six Sigma process identified eight key steps in
      the transfer of patients from general medical floors to critical care areas.
      Preintervention data and a root-cause analysis helped to establish the goal
      transfer-time limits of 3 h for any individual transfer and 90 min for the
      average of all transfers. CONCLUSIONS: The Six Sigma approach is a problem
      solving methodology that resulted in almost a 60% reduction in patient transfer
      time from a general medical floor to a critical care area. The Six Sigma process
      is a feasible method for implementing healthcare related quality of care
      projects, especially those that are complex.

PMID- 23552176
TI  - A year in review in Minerva Anestesiologica 2012.

PMID- 23552177
TI  - Double site saturation mutagenesis of the human cytochrome P450 2D6 results in
      regioselective steroid hydroxylation.
AB  - The human cytochrome P450 2D6 (CYP2D6) is one of the major human drug
      metabolizing enzymes and acts preferably on substrates containing a basic
      nitrogen atom. Testosterone - just as other steroids - is an atypical substrate
      and only poorly metabolized by CYP2D6. The present study intended to investigate
      the influence of the two active site residues 216 and 483 on the capability of
      CYP2D6 to hydroxylate steroids such as for example testosterone. All 400 possible
      combinatorial mutations at these two positions have been generated and expressed
      individually in Pichia pastoris. Employing whole-cell biotransformations coupled
      with HPLC-MS analysis the testosterone hydroxylase activity and regioselectivity
      of every single CYP2D6 variant was determined. Covering the whole sequence space,
      CYP2D6 variants with improved activity and so far unknown regio-preference in
      testosterone hydroxylation were identified. Most intriguingly and in contrast to
      previous literature reports about mutein F483I, the mutation F483G led to
      preferred hydroxylation at the 2beta-position, while the slow formation of 6beta
      hydroxytestosterone, the main product of wild-type CYP2D6, was further reduced.
      Two point mutations have already been sufficient to convert CYP2D6 into a steroid
      hydroxylase with the highest ever reported testosterone hydroxylation rate for
      this enzyme, which is of the same order of magnitude as for the conversion of the
      standard substrate bufuralol by wild-type CYP2D6. Furthermore, this study is also
      an example for efficient human CYP engineering in P. pastoris for biocatalytic
      applications and to study so far unknown pharmacokinetic effects of individual
      and combined mutations in these key enzymes of the human drug metabolism.

PMID- 23552178
TI  - Elevated serum level of IL-33 and sST2 in patients with ankylosing spondylitis:
      associated with disease activity and vascular endothelial growth factor.
AB  - OBJECTIVE: Interleukin (IL)-33 is a cytokine belonging to the IL-1 family and was
      recently identified as a ligand for ST2, which belongs to the IL-1 receptor (IL
      1R) family. In this study, we aimed to investigate the possible
      pathophysiological role of IL-33/sST2 in ankylosing spondylitis (AS). METHODS:
      The levels of IL-33/sST2 and vascular endothelial growth factor in serum samples
      of 140 patients with AS and 90 controls were measured by enzyme-linked
      immunosorbent assay. Erythrocyte sedimentation rate, C-reactive protein level,
      and human leukocyte antigen B27 were measured by standard laboratory techniques.
      Disease activity in AS was measured by the Bath Ankylosing Spondylitis Disease
      Activity Index. Hip involvement, peripheral arthritis, and eye involvement were
      also recorded. RESULTS: The serum levels of IL-33/sST2 were remarkably higher in
      the patients with AS than the healthy groups and significantly correlated with
      vascular endothelial growth factor and the Bath Ankylosing Spondylitis Disease
      Activity Index. The sST2 levels correlated with erythrocyte sedimentation rate, C
      reactive protein, platelet, and human leukocyte antigen B27. Elevated levels of
      IL-33/sST2 were detected in the patients with peripheral arthritis, and sST2 were
      detected to be increased in the patients with hip involvement. By contrast,
      levels of IL-33 but not sST2 increased in the patients with eye involvement.
      CONCLUSION: IL-33/sST2 may regulate the immunological or inflammatory process of
      AS.

PMID- 23552179
TI  - Sodium bicarbonate versus isotonic saline for the prevention of contrast-induced
      nephropathy in patients with diabetes mellitus undergoing coronary angiography
      and/or intervention: a multicenter prospective randomized study.
AB  - INTRODUCTION: Contrast-induced nephropathy (CIN) is a leading cause of acute
      renal failure and affects mortality and morbidity. Although the incidence of CIN
      is quite low in the general population, CIN incidence is significantly increased
      in patients with diabetes mellitus (DM). OBJECTIVES: We compared the efficacy of
      prophylactic use consisting of a saline infusion or a sodium bicarbonate infusion
      for the prevention of CIN in patients with DM. MATERIALS AND METHODS: A total of
      195 DM patients who had unselected renal function were randomized into 2 groups:
      101 patients were assigned to saline infusion, and 94 patients were assigned to
      bicarbonate infusion. The primary end point was the maximum increase in the serum
      creatinine (SCr) level, whereas the secondary end point was the development of
      CIN after the procedure. RESULTS: The maximum increase in SCr levels was
      significantly lower in the saline group than in the bicarbonate group: -0.03
      mg/dL (IQR, -0.09 to 0.10 mg/dL) versus 0.02 mg/dL (IQR, -0.09 to 0.13 mg/dL) (P
      = 0.014). The rate of CIN was significantly lower in the saline group than in the
      bicarbonate group (5.9% vs 16%, P = 0.024). In the subset of study participants
      with a baseline creatinine clearance of less than 60 mL/min, the maximum increase
      in SCr levels was significantly lower, -0.08 mg/dL (IQR, -0.13 to -0.04 mg/dL),
      in the saline group than in the bicarbonate group, 0.03 mg/dL (IQR, -0.13 to 0.12
      mg/dL) (P = 0.004). CONCLUSIONS: The use of prophylactic hydration with isotonic
      saline before coronary procedures may decrease SCr levels and reduce the
      incidence of CIN in patients with DM with unselected renal functions to a greater
      extent than sodium bicarbonate can.

PMID- 23552180
TI  - Treating older adults with schizophrenia: challenges and opportunities.
AB  - Schizophrenia affects people of all age groups. Treatment plans for older adults
      with schizophrenia must consider the effects of age on the course of the illness
      as well as on the response to antipsychotics and to psychosocial interventions.
      Positive symptoms of schizophrenia tend to become less severe, substance abuse
      becomes less common, and mental health functioning often improves.
      Hospitalizations are more likely to be due to physical problems rather than
      psychotic relapses. Physical comorbidity is a rule, however, and older age is a
      risk factor for most side effects of antipsychotics, including metabolic syndrome
      and movement disorders. We recently reported high rates of adverse events and
      medication discontinuation along with limited effectiveness of commonly used
      atypical antipsychotics in older adults. Psychosocial interventions such as
      cognitive behavioral social skills training are efficacious in improving
      functioning in older adults with schizophrenia. In formulating treatment plans
      for this population, a balanced approach combining cautious antipsychotic
      medication use with psychosocial interventions is recommended. Antipsychotic
      medications should generally be used in lower doses in older adults. Close
      monitoring for side effects and effectiveness of the medications and a watchful
      eye on their risk:benefit ratio are critical. In a minority of patients it may be
      possible to discontinue medications. Sustained remission of schizophrenia after
      decades of illness is not rare, especially in persons who receive appropriate
      treatment and psychosocial support-there can be light at the end of a long
      tunnel. 

PMID- 23552181
TI  - Quantum interference and Aharonov-Bohm oscillations in topological insulators.
AB  - Topological insulators (TIs) have an insulating bulk but a metallic surface. In
      the simplest case, the surface electronic structure of a three-dimensional (3D)
      TI is described by a single two-dimensional (2D) Dirac cone. A single 2D Dirac
      fermion cannot be realized in an isolated 2D system with time-reversal symmetry,
      but rather owes its existence to the topological properties of the 3D bulk
      wavefunctions. The transport properties of such a surface state are of
      considerable current interest; they have some similarities with graphene, which
      also realizes Dirac fermions, but have several unique features in their response
      to magnetic fields. In this review we give an overview of some of the main
      quantum transport properties of TI surfaces. We focus on the efforts to use
      quantum interference phenomena, such as weak anti-localization and the Aharonov
      Bohm effect, to verify in a transport experiment the Dirac nature of the surface
      state and its defining properties. In addition to explaining the basic ideas and
      predictions of the theory, we provide a survey of recent experimental work.

PMID- 23552183
TI  - Usability of digital media in patients with COPD: a pilot study.
AB  - BACKGROUND: Digital media can be integrated in tele-monitoring solutions, serving
      as the main interface between the patient and the caregiver. Consequently, the
      selection of the most appropriate digital medium for the specified target group
      is critical to ensure compliance with the tele-monitoring system. OBJECTIVES:
      This pilot study aims to gather insights from patients with chronic obstructive
      pulmonary disease (COPD) on the ease-of-use, efficacy, effectiveness, and
      satisfaction of different types of digital media. METHODS: Five off-the-shelf
      digital media devices were tested on nine patients at CIRO+ in Horn, The
      Netherlands. Usability was evaluated by asking patients to use each device to
      answer questions related to their symptoms and health status. Subsequently,
      patients completed a paper-based device usability questionnaire, which assessed
      prior experience with digital media, device dimensions, device controllability,
      response speed, screen readability, ease-of-use, and overall satisfaction. After
      testing all the devices, patients ranked the devices according to their
      preference. RESULTS: We identified the netbook as the preferred type of device
      due to its good controllability, fast response time, and large screen size. The
      smartphone was the least favorite device as patients found the size of the screen
      to be too small, which made it difficult to interact with. CONCLUSION: The pilot
      study has provided important insights to guide the selection of the most
      appropriate type of digital medium for implementation in tele-monitoring
      solutions for patients with COPD. As the digital medium is an important interface
      to the patient in tele-monitoring solutions, it is essential that patients feel
      motivated to interact with the digital medium on a regular basis.

PMID- 23552182
TI  - DHEA enhances emotion regulation neurocircuits and modulates memory for emotional
      stimuli.
AB  - Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant,
      and antiglucocorticoid properties. It is endogenously released in response to
      stress, and may reduce negative affect when administered exogenously. Although
      there have been multiple reports of DHEA's antidepressant and anxiolytic effects,
      no research to date has examined the neural pathways involved. In particular,
      brain imaging has not been used to link neurosteroid effects to emotion
      neurocircuitry. To investigate the brain basis of DHEA's impact on emotion
      modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15)
      and underwent 3T fMRI while performing the shifted-attention emotion appraisal
      task (SEAT), a test of emotional processing and regulation. Compared with
      placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced
      connectivity between the amygdala and hippocampus, and enhanced activity in the
      rACC. These activation changes were associated with reduced negative affect. DHEA
      reduced memory accuracy for emotional stimuli, and also reduced activity in
      regions associated with conjunctive memory encoding. These results demonstrate
      that DHEA reduces activity in regions associated with generation of negative
      emotion and enhances activity in regions linked to regulatory processes.
      Considering that activity in these regions is altered in mood and anxiety
      disorders, our results provide initial neuroimaging evidence that DHEA may be
      useful as a pharmacological intervention for these conditions and invite further
      investigation into the brain basis of neurosteroid emotion regulatory effects.

PMID- 23552184
TI  - I spy with my little eye something beginning with O: looking at what the myth of
      'doing the observations' means in mental health nursing culture.
AB  - Those who are familiar with psychiatric inpatient settings will be aware of the
      expressions 'doing the obs', 'being on checks' and 'special observations'. That
      is because the task of observing patients is seen as being pivotal to the mental
      health nursing role. This paper describes an ethnographic research project that
      offers a rethinking of psychiatric observation. The author uses data from an
      ethnographic research project to provide an examination of the structure, process
      and outcome of this seemingly straightforward nursing task and explores how
      'doing the obs' has additional symbolic and cultural meaning similar to what
      Barthes terms myth. The symbolic connotations are numerous and wide-ranging and
      expose a practice that could be said to punctuate daily activities and an
      ordering of relationships between nurses and services users. The classic
      sociological issues of status, power and containment are all relevant, yet
      rethought. The use of ethnographic research allowed the author to focus on the
      more symbolic cultural dynamics and develop five initial ethnographic themes
      concerning the constituting experience of watching and being watched.

PMID- 23552185
TI  - Helminth communities in murid rodents from southern and northern localities in
      Lao PDR: the role of habitat and season.
AB  - The helminth communities of wild murid rodents were investigated in Luang Prabang
      and Champasak province, Lao PDR. Thirteen species of rodents (404 individuals)
      were infected by 19 species of parasites (2 trematode, 3 cestode, 14 nematode
      species). Four of the recorded helminth species (Echinostoma malayanum,
      Raillietina sp., Hymenolepis diminuta and H. nana) are known to cause potential
      zoonotic helminthiases of medical importance in the South-East Asian region.
      Individual helminth infection was significantly higher in the wet season. Habitat
      significantly influenced individual helminth species richness and individual
      helminth abudance, with a decrease of individual helminth species richness and
      individual helminth abundance from forest habitat to agricultural and human
      settlement habitats. The reduction of helminth diversity and abundance is
      discussed in relation to the ongoing increase of human influence on habitats in
      Lao PDR. 

PMID- 23552186
TI  - Indirect RKKY interaction between localized magnetic moments in armchair graphene
      nanoribbons.
AB  - A form of indirect Ruderman-Kittel-Kasuya-Yosida (RKKY)-like coupling between
      magnetic on-site impurities in armchair graphene nanoribbons is studied
      theoretically. The calculations are based on a tight-binding model for a finite
      nanoribbon system with periodic boundary conditions. A pronounced Friedel
      oscillation-like dependence of the coupling magnitude on the impurity position
      within the nanoribbon resulting from quantum size effects is found and
      investigated. In particular, the distance dependence of coupling is analysed. For
      semiconducting nanoribbons, this dependence is exponential-like, resembling the
      Bloembergen-Rowland interaction. For metallic nanoribbons, interesting behaviour
      is found for finite length systems, in which zero-energy states make an important
      contribution to the interaction. In such situations, the coupling decay with
      distance can then be substantially slower.

PMID- 23552187
TI  - Direct and accurate patterning of plasmonic nanostructures with ultrasmall gaps.
AB  - We report an improved method to directly and accurately fabricate plasmonic
      nanostructures with ultrasmall gaps. The fabrication is based on high-resolution
      focused ion beam milling with closely packed nanoring patterns. With fine and
      precise adjustment of the ion beam, elegant plasmonic nanostructures with
      ultrasmall dimensions down to 10 nm are achieved. We also show that the gap
      dimensions have a strong effect on the optical reflectance and transmittance of
      the plasmonic nanostructures. Measured results show reasonable agreement with
      finite-difference time-domain calculations. Our approach could find promising
      applications in plasmon-assisted sensing and surface-enhanced spectroscopy.

PMID- 23552188
TI  - Endobronchial endometriosis presenting as central-type lung cancer: a case
      report.
AB  - A 45-year-old female patient was referred to our hospital for complaining of
      dyspnea and coughing in the past four months. The computed tomography scanning
      demonstrated a central lesion in the upper lobe of the left lung close to the
      hilar, and the subsequent bronchoscopy revealed a polypoid lesion of the distal
      of the left main bronchus. This patient was diagnosed clinically as "possibly
      central-type lung cancer". However, the pathologic result of the surgically
      excised polypoid lesion was endobronchial endometriosis. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1077439085928525.

PMID- 23552189
TI  - Practical applications of small-angle neutron scattering.
AB  - Recent improvements in beam-line accessibility and technology have led to small
      angle neutron scattering (SANS) becoming more frequently applied to materials
      problems. SANS has been used to study the assembly, dispersion, alignment and
      mixing of nanoscale condensed matter, as well as to characterise the internal
      structure of organic thin films, porous structures and inclusions within steel.
      Using time-resolved SANS, growth mechanisms in materials systems and soft matter
      phase transitions can also be explored. This review is intended for newcomers to
      SANS as well as experts. Therefore, the basic knowledge required for its use is
      first summarised. After this introduction, various examples are given of the
      types of soft and hard matter that have been studied by SANS. The information
      that can be extracted from the data is highlighted, alongside the methods used to
      obtain it. In addition to presenting the findings, explanations are provided on
      how the SANS measurements were optimised, such as the use of contrast variation
      to highlight specific parts of a structure. Emphasis is placed on the use of
      complementary techniques to improve data quality (e.g. using other scattering
      methods) and the accuracy of data analysis (e.g. using microscopy to separately
      determine shape and size). This is done with a view to providing guidance on how
      best to design and analyse future SANS measurements on materials not listed
      below.

PMID- 23552190
TI  - Effect of negative attributions on depressive symptoms of patients with coronary
      heart disease after controlling for physical functional impairment.
AB  - OBJECTIVES: Negative attributional style (NAS), or tendency to explain negative
      events through internal, stable, and global causes, has proved to be an important
      predictor of depressive symptoms and poor health, including coronary heart
      disease (CHD). The goal of this two-wave longitudinal study was to look at
      whether depressive symptoms are caused by or are a consequence of this style in a
      sample of patients with CHD while controlling for the effect of physical
      functional impairment on the development of these symptoms. METHODS: Ninety-one
      patients, who had just suffered a first cardiac episode, were evaluated on NAS,
      depressive symptoms and functional capacity (measured in metabolic equivalent
      levels or METs) both on the first and on last day of an 8-week cardiac
      rehabilitation programme. RESULTS: Globality dimension of NAS at Time 1 predicted
      depressive symptoms at Time 2 after controlling for both depressive symptoms and
      METs at Time 1. However, depressive symptoms at Time 1 could not predict any
      dimension of this style at Time 2. CONCLUSIONS: These results seem to support
      that negative attributions about the disease are one of the causes contributing
      to the development of depression and not a consequence of it, and also suggest
      that intervention programme should be aimed not only at reducing depressive
      symptoms, but also at replacing stable and global attributions of negative
      situations with more unstable and specific explanations. STATEMENT OF
      CONTRIBUTION: What is already known on this subject? Negative attributional style
      (NAS) is an important predictor of depressive symptoms.Depressive symptoms worsen
      the diagnosis of coronary heart disease (CHD) patients. What does this study add?
      Globality dimension predicts depression in patients with CHD after controlling
      for functional capacity. Negative attributions contribute to the development of
      depression and are not a consequence of it.

PMID- 23552191
TI  - Polynuclear lanthanide (Ln) complexes of a tri-functional hydrazone ligand-
      mononuclear (Dy), dinuclear (Yb, Tm), tetranuclear (Gd), and hexanuclear (Gd, Dy,
      Tb) examples.
AB  - The lanthanide coordination chemistry of a tri-functional vanillin-hydrazone
      oxime ligand reveals a variety of different products, depending on reaction
      conditions, with mono-nuclear (Dy), dinuclear (Yb, Tm), tetranuclear (Gd) and
      hexanuclear (Gd, Tb, Dy) examples. The Ln6 (Ln = Gd, Dy, Tb) complexes form in
      the presence of both triethylamine and acetic acid, and have unique, flat
      hexanuclear structures built on a MU3-O bridged triangular core, with the six
      lanthanide ions bridged further through MU-acetate and MU-Ohydrazone connections
      in an expanded fused triangular array. Similar reaction conditions with Yb(III)
      and Tm(III) lead preferentially to dinuclear systems, while in the presence of a
      competitive benzoate ligand a rectangular Gd4 complex results. Variable
      temperature DC magnetic data for the Gd(III) complexes reveal weak
      antiferromagnetic exchange. AC magnetic data on the other polynuclear complexes
      down to 2 K, both in the absence and presence of external bias fields, revealed
      no significant out of phase signals normally indicative of SMM behavior. However,
      the mononuclear Dy(III) complex shows frequency dependent AC signals and maxima
      in the temperature range 2-20 K in the presence of an external bias field,
      indicative of SMM behaviour, with Ueff = 36(1) K, and tau0 = 4.4(2) * 10(-6) s.

PMID- 23552192
TI  - CuCl-catalyzed ortho trifluoromethylation of arenes and heteroarenes with a
      pivalamido directing group.
AB  - The CuCl catalyzed direct trifluoromethylation of sp(2) C-H bonds has been
      realized, using the Togni reagent as the CF3 source. This reaction achieves the
      goal of regio-selectively converting C-H into C-CF3 with ecological and readily
      available starting materials.

PMID- 23552194
TI  - Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and
      factors associated with poor prognosis in a murine breast cancer model.
AB  - BACKGROUND: Several treatment alternatives are available for primary breast
      cancer, although those for metastatic disease or inflammation associated with
      tumor progression are ineffective. Therefore, there is a great need for new
      therapeutic alternatives capable of generating an immune response against
      residual tumor cells, thus contributing to eradication of micrometastases and
      cancer stem cells. The use of complex natural products is an excellent
      therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral
      Latin-American Indian populations. METHODS: The present study evaluated
      cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich
      fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in
      vitro were mitochondrial membrane depolarization, phosphatidylserine
      externalization, caspase 3 activation, DNA fragmentation, and clonogenic
      activity. The parameters evaluated in vivo were tumor growth, leukocyte number,
      metastatic cell number, and cytokine production by flow cytometry. RESULTS: The
      in vitro results showed that the P2Et fraction induced apoptosis with
      mitochondrial membrane potential loss, phosphatidylserine externalization,
      caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1
      cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of
      diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased
      numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the
      number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL
      6) serum levels were found, which are events associated with a poor prognosis.
      The P2Et fraction exerts its activity on the primary tumor, reduces cell
      migration to distant organs, and decreases IL-6 serum levels, implying tumor
      microenvironment mechanisms. CONCLUSIONS: Overall, the P2Et fraction lessens risk
      factors associated with tumor progression and diminishes primary tumor size,
      showing good potential for use as an adjuvant in breast cancer ER(+) treatment.

PMID- 23552195
TI  - Selection of reference genes for quantitative real-time PCR normalisation in
      adipose tissue, muscle, liver and mammary gland from ruminants.
AB  - The reliability of reverse transcription quantitative real-time PCR (RT-qPCR)
      depends on normalising the mRNA abundance using carefully selected, stable
      reference genes. Our aim was to propose sets of reference genes for normalisation
      in bovine or caprine adipose tissue (AT), mammary gland, liver and muscle. All of
      these tissues contribute to nutrient partitioning and metabolism and, thus, to
      the profitability of ruminant productions (i.e. carcasses, meat and milk). In
      this study, eight commonly used reference genes that belong to different
      functional classes (CLN3, EIF3K, MRPL39, PPIA, RPLP0, TBP, TOP2B and UXT) were
      analysed using the geNorm procedure to determine the most stable reference genes
      in bovine and/or caprine tissues. Abundances and rankings of reference genes
      varied between tissues, species and the combination of tissues and/or species.
      Therefore, we proposed 29 sets of reference genes that differed depending on the
      tissue and/or species. As examples of the 29 sets, EIF3K, TOP2B and UXT were
      proposed as the most stable reference genes in bovine AT; UXT, EIF3K and RPLP0
      were the most stable reference genes in bovine and caprine AT. The optimal number
      of reference genes for data normalisation was 3 for 27 of the proposed 29 sets.
      In two of the 29 sets, four to five reference genes were necessary for data
      normalisation when the number of studied tissues was increased. For example, UXT,
      EIF3K, TBP, TOP2B and CLN3 were required for data normalisation in bovine mammary
      gland, AT, muscle and liver. We have evaluated some of our proposed sets of
      reference genes for the normalisation of CD36 gene expression. Normalisation
      using the three most stable reference genes has revealed downregulation of CD36
      gene expression in bovine mammary gland by a concentrate-based diet that is
      supplemented with sunflower oil and upregulation of CD36 gene expression in
      caprine liver by including a rapidly degradable starch in the diet. The dietary
      regulation of the gene expression of CD36 has been erased by normalisation with
      the least stable reference genes, which may result in misinterpretation of CD36
      gene regulation. To conclude, our results provide valuable reference gene sets
      for other studies that aim to measure tissue and/or species-specific mRNA
      abundance in ruminants. 

PMID- 23552197
TI  - Research, evidence, and results of better healthcare through quality improvement
      efforts.

PMID- 23552198
TI  - The safety net after health reform: needed more than ever.

PMID- 23552196
TI  - Pig immune response to general stimulus and to porcine reproductive and
      respiratory syndrome virus infection: a meta-analysis approach.
AB  - BACKGROUND: The availability of gene expression data that corresponds to pig
      immune response challenges provides compelling material for the understanding of
      the host immune system. Meta-analysis offers the opportunity to confirm and
      expand our knowledge by combining and studying at one time a vast set of
      independent studies creating large datasets with increased statistical power. In
      this study, we performed two meta-analyses of porcine transcriptomic data: i)
      scrutinized the global immune response to different challenges, and ii)
      determined the specific response to Porcine Reproductive and Respiratory Syndrome
      Virus (PRRSV) infection. To gain an in-depth knowledge of the pig response to
      PRRSV infection, we used an original approach comparing and eliminating the
      common genes from both meta-analyses in order to identify genes and pathways
      specifically involved in the PRRSV immune response. The software Pointillist was
      used to cope with the highly disparate data, circumventing the biases generated
      by the specific responses linked to single studies. Next, we used the Ingenuity
      Pathways Analysis (IPA) software to survey the canonical pathways, biological
      functions and transcription factors found to be significantly involved in the pig
      immune response. We used 779 chips corresponding to 29 datasets for the pig
      global immune response and 279 chips obtained from 6 datasets for the pig
      response to PRRSV infection, respectively. RESULTS: The pig global immune
      response analysis showed interconnected canonical pathways involved in the
      regulation of translation and mitochondrial energy metabolism. Biological
      functions revealed in this meta-analysis were centred around translation
      regulation, which included protein synthesis, RNA-post transcriptional gene
      expression and cellular growth and proliferation. Furthermore, the oxidative
      phosphorylation and mitochondria dysfunctions, associated with stress signalling,
      were highly regulated. Transcription factors such as MYCN, MYC and NFE2L2 were
      found in this analysis to be potentially involved in the regulation of the immune
      response. The host specific response to PRRSV infection engendered the activation
      of well-defined canonical pathways in response to pathogen challenge such as
      TREM1, toll-like receptor and hyper-cytokinemia/ hyper-chemokinemia signalling.
      Furthermore, this analysis brought forth the central role of the crosstalk
      between innate and adaptive immune response and the regulation of anti
      inflammatory response. The most significant transcription factor potentially
      involved in this analysis was HMGB1, which is required for the innate recognition
      of viral nucleic acids. Other transcription factors like interferon regulatory
      factors IRF1, IRF3, IRF5 and IRF8 were also involved in the pig specific response
      to PRRSV infection. CONCLUSIONS: This work reveals key genes, canonical pathways
      and biological functions involved in the pig global immune response to diverse
      challenges, including PRRSV infection. The powerful statistical approach led us
      to consolidate previous findings as well as to gain new insights into the pig
      immune response either to common stimuli or specifically to PRRSV infection.

PMID- 23552199
TI  - Addressing social determinants to improve healthcare quality and reduce cost.
AB  - Most healthcare quality improvement and cost reduction efforts currently focus on
      care processes, or transitions-for example, the hospital discharge process. While
      identification and adoption of best practices to address these aspects of
      healthcare are essential, more is needed for systems that serve vulnerable
      populations: to account for social factors that often inhibit patients' ability
      to take full advantage of available healthcare. Our urban safety net healthcare
      system developed and implemented an innovative quality improvement approach. The
      programs, Guided Chronic Care(TM) , and Passport to Wellness, use Assertive Care
      and provide social support for patients between medical encounters, enabling
      patients to make better use of the healthcare system and empowering them to
      better manage their conditions. RESULTS: The majority of patients reported
      problems with mobility and nearly half reported anxiety or depression. Early
      indications show improved quality of care and significant reduction in costs.
      Challenges encountered and lessons learned in implementing the programs are
      described, to assist others developing similar interventions.

PMID- 23552200
TI  - A quality improvement framework for equity in cardiovascular care: results of a
      national collaborative.
AB  - Disparities in the quality of cardiovascular care provided to minorities have
      been well documented, but less is known about the use of quality improvement
      methods to eliminate these disparities. Measurement is also often impeded by a
      lack of reliable patient demographic data. The objective of this study was to
      assess the ability of hospitals with large minority populations to measure and
      improve the care rendered to Black and Hispanic patients. The Expecting Success:
      Excellence in Cardiac Care project utilized the standardized collection of self
      reported patient race, ethnicity, and language data to generate stratified
      performance measures for cardiac care coupled with evidence-based practice tools
      in a national competitively selected sample of 10 hospitals with high cardiac
      volumes and largely minority patient populations. Main outcomes included changes
      in nationally recognized measures of acute myocardial infarction and heart
      failure quality of care and 2 composite measures, stratified by patient
      demographic characteristics. Quality improved significantly at 7 of the 10
      hospitals as gauged by composite measures (p < .05), and improvements exceeded
      those observed nationally for all hospitals. Three of 10 hospitals found racial
      or ethnic disparities which were eliminated in the course of the project.
      Clinicians and institutions were able to join the standardized collection of self
      reported patient demographic data to evidence-based measures and quality
      improvement tools to improve the care of minorities and eliminate disparities in
      care. This framework may be replicable to ensure equity in other clinical areas.

PMID- 23552201
TI  - Standardizing race, ethnicity, and preferred language data collection in hospital
      information systems: results and implications for healthcare delivery and policy.
AB  - The Institute of Medicine has identified the need for healthcare organizations to
      collect standardized demographic data as a step toward reducing healthcare
      disparities. This observational study of patients discharged from a large
      academic medical center between 2005 and 2009, evaluates an organizational effort
      to standardize demographic data collection, characterizes limitations of the
      implementation, and assesses its utility in quality improvement and disparity
      reduction efforts. Primary measures include percentages of inpatient discharges
      with unknown race, ethnicity, and language data. Secondary measures include
      "ideal" cardiovascular care and readmission rates. From 2005 to 2009, the
      proportion of discharges with unknown race, ethnicity, or preferred language data
      decreased significantly. Among discharges with known ethnicity in 2009,
      Hispanic/Latino patients were significantly more likely to decline to specify
      their race or designate their race as a "Multiracial: Other Combination." No
      significant differences in ideal cardiovascular care were observed across
      demographic groups. Differences in readmission rates were observed among some
      groups. A provider organization can effectively standardize demographic data
      collection practices for use in quality improvement efforts. Current federal race
      categories are of limited utility for persons of Hispanic/Latino ethnicity, and
      performance measurement approaches that exclude demographic variables may fail to
      address healthcare disparities.

PMID- 23552202
TI  - Improving the quality of language services delivery: findings from a hospital
      quality improvement initiative.
AB  - Over 24 million individuals in the United States speak English "less than very
      well" and are considered limited English proficient (LEP). Due to challenges
      inherent in patient-provider interactions with LEP patients, LEP individuals are
      at risk for a wide array of negative health consequences. Evidence suggests that
      having an interpreter present to facilitate interactions between LEP patients and
      health professionals can mitigate many of these disparities. This article
      presents the results and lessons learned from Speaking Together: National
      Language Services Network, a quality improvement (QI) collaborative of the Robert
      Wood Johnson Foundation to improve the quality of language services (LS) in
      hospitals. Using five LS performance metrics, hospitals were able to demonstrate
      that meaningful improvement was possible through targeted QI efforts. By the end
      of the collaborative, each of the hospitals demonstrated improvement by more than
      five percentage points on at least one of the five recorded quality metrics.
      Lessons learned from this work, such as the helpful use of quality metrics to
      track performance, and the engagement of physician champions and executive
      leadership to promote improvement can be utilized in hospitals across the country
      because they seek to improve care for LEP patients.

PMID- 23552203
TI  - Improving patient safety to reduce preventable deaths: the case of a California
      safety net hospital.
AB  - Preventable deaths occur when signs and symptoms of risk and decline are not
      detected yet are present many hours prior to a deteriorating course. Rapid
      responses teams (RRTs), also referred to as medical emergency teams (METs) were
      introduced to improve patient safety by preventing code arrests and death. This
      research using a case study methodology describes a nurse-led RRT, developed at a
      large, safety net, teaching hospital in California. Safety-net hospitals are
      challenged to deliver care and meet the complex needs of vulnerable patient
      populations. This hospital is a mission driven organization that is focused on
      the patient and the needs of underserved populations. To respond to the call for
      reform for patient safety and reduce adverse events, the organization adopted
      RRTs, early recognition rounds by RRT registered nurses (RNs) and the use of
      trigger alerts by nursing assistants (NAs) to expand the surveillance and
      identification of patients most at risk of clinical deterioration. Collaboration
      with interns and residents (house staff) facilitated their involvement and
      response to RRT calls. Using quality data from 2005 to 2010, findings from this
      patient safety innovation address RRT utilization, frequency of non-ICU code
      arrests, hospital mortality, and post-arrest survival outcomes.

PMID- 23552204
TI  - A multifaceted approach to spreading palliative care consultation services in
      California public hospital systems.
AB  - Historically, California's 17 public hospital systems-those that are county owned
      and operated, and those University of California medical centers with the mandate
      to serve low income, vulnerable populations-have struggled to implement
      Palliative Care Consultation Services (PCCS)-this, despite demonstrated need for
      these services among the uninsured and Medicaid populations served by these
      facilities. Since 2008, through a collaborative effort of a foundation, a
      palliative care training center, and a nonprofit quality improvement
      organization, the Spreading Palliative Care in Public Hospitals initiative
      (SPCPH) has resulted in a 3-fold increase in the number of California public
      hospitals providing PCCS, from 4 to 12. The SPCPH leveraged grant funding, the
      trusted relationships between California public hospitals and their quality
      improvement organization, technical assistance and training, peer support and
      learning, and a tailored business case demonstrating the financial/resource
      utilization benefits of dedicated PCCS. This article describes the SPCPH's
      distinctive design, features of the public hospital PCCS, patient and team
      characteristics, and PCCS provider perceptions of environmental factors, and
      SPCPH features that promoted or impeded their success. Lessons learned may have
      implications for other hospital systems undertaking implementation of palliative
      care services.

PMID- 23552205
TI  - STAT--how to make every minute count.
AB  - Several years ago, our community teaching hospital identified a need to improve
      patient care by streamlining the study performance workflow and hastening
      communication of critical study results to clinicians. "STAT" studies are a
      carefully selected subset of imaging studies that are prioritized due to their
      utility in assessing for emergent conditions including cerebrovascular accidents,
      pneumoperitoneum, and cardiac arrest. We describe the multiyear process of data
      collection, analysis, and departmental and hospital-wide system changes that
      significantly improved result times. Relatively simple policy changes, such as
      the distribution of STAT beepers to the team members and creating color-coded
      worklists, drastically reduced delays.

PMID- 23552206
TI  - Hybrid Capture II testing for high-risk human papillomavirus DNA in the follow-up
      of women treated for high-grade cervical intraepithelial neoplasia.
AB  - OBJECTIVE: This study aimed to estimate and compare the validity of high-risk
      human papillomavirus DNA (HR-HPV DNA) testing using Hybrid Capture II with and
      without Pap cytological examination in the detection of incident high-grade
      cervical intraepithelial neoplasia (CIN 2+) after treatment. MATERIALS AND
      METHODS: A total of 1,608 women undergoing ablative or excisional treatment were
      recruited to the study between May 2001 and June 2005, of whom 985 women were
      treated for CIN 2+. High-risk HPV DNA tests and Pap smears were performed once in
      every 6 months for 24 months after treatment. RESULTS: A total of 888 women were
      eligible for analysis. High-grade cervical intraepithelial neoplasia was detected
      in 22 women (2.5%) for the 24 months after treatment. The sensitivity for CIN 2+
      detection with cytological diagnosis ranged from 43% to 100%, from 67% to 100%
      for HR-HPV DNA test, and from 67% to 100% for both tests combined. The
      specificity of cytological diagnosis ranged from 94% to 97%, from 75% to 84% for
      HR-HPV DNA test, and from 80% to 82% for both tests combined. The positive
      predictive value for cytological diagnosis ranged from 8% to 30%, from 4% to 14%
      for HR-HPV DNA test, and from 4% to 11% for both tests combined. The negative
      predictive value was 99% or greater for cytological diagnosis alone, HR-HPV DNA
      test alone, or for both tests combined. CONCLUSIONS: As histologically proven CIN
      2+ after treatment for this group of women was low, adding HR-HPV DNA testing to
      Pap smear did not increase the detection of CIN 2+ or enhance the negative
      predictive value of cytological diagnosis alone.

PMID- 23552207
TI  - Human papillomavirus DNA and Pap tests: the need for cotesting in opportunistic
      setting during the transition time.

PMID- 23552208
TI  - The patterns and criteria of vaginal douching and the risk of preterm labor among
      upper Egypt women.
AB  - OBJECTIVES: Our study identifies vaginal douching as a risk factor for preterm
      labor and specifies the risk according to the method, frequency, nature, and
      timing of douching. MATERIALS AND METHODS: This is a hospital-based case-control
      study. A total of 480 women were recruited. Women were classified into case group
      (history of preterm labor) and control group (no history of preterm labor). An
      interview questionnaire was administered, which included participants' data and
      criteria of douching practice. RESULTS: Among participants who regularly douched
      (73.13%), 281 (80.06%) used it for cleanliness and religious considerations.
      Women who have been regularly douched were at higher risk of preterm labor
      (adjusted odds ratio [OR] = 1.9; 95% CI = 1.078-3.278; p = .026). The method
      (fingers vs pump) and the frequency of douching were significantly relevant. The
      risk of douching during pregnancy was borderline (adjusted OR = 2.1; 95% CI =
      1.001-4.446; p =.05). Douching several times per day has an OR of 4.05 (95% CI =
      1.196-13.737; p =.025) when compared with the monthly frequency. CONCLUSIONS:
      Vaginal douching is associated with higher risk of preterm labor. We recommend
      that the risk of asymptomatic bacterial vaginosis should be considered.

PMID- 23552209
TI  - Androgen insensitivity syndrome with gynandroblastoma and vulvar leiomyoma: case
      report and literature review.
AB  - OBJECTIVE: This study aimed to describe a rare case of androgen insensitivity
      syndrome (AIS) in association with gynandroblastoma and vulvar leiomyomata.
      MATERIALS AND METHODS: The patient was a 64-year-old phenotypically female person
      with 46 XY chromosomal karyotypes who presented with a chief complaint of
      abdominal distension of 1-month duration. She had 2 vulvar masses for more than
      20 years and had experienced life-long (untreated) amenorrhea. History and
      physical examination findings showed the patient to be 175 cm in height, with
      normal breast development, and a lack of pubic or axillary hair. Serum levels
      were as follows: testosterone, 1,980 ng/dL; estradiol, 1,380.8 pg/mL. RESULTS: In
      combination with clinical findings, a diagnosis of complete AIS was made. The
      patient subsequently underwent surgery, during which the bilateral vulvar masses
      and the rudimentary uterus, right sex gland, and left side of the tumor were
      resected. Histological examination of the tumor revealed a mass composed
      primarily of juvenile-type granulosa cells, admixed with a Sertoli cell component
      that comprised less than 50% of the tumor. The right side of the gonad had an
      ovarian-like cortex and was considered to be an undeveloped ovary. The left and
      right side of the vulvar masses were diagnosed with leiomyomas. CONCLUSIONS:
      Patients with AIS should be monitored closely because these patients may also
      experience gonadal tumors. When confronted with gynandroblastoma, close attention
      should be paid to the patient's endocrinologic status, and comprehensive
      endocrinologic analyses should be conducted to make correct treatment decisions.

PMID- 23552210
TI  - Surgical management of vestibular schwannoma: attempted preservation of hearing
      and facial function.
AB  - BACKGROUND: Vestibular schwannomas are benign tumours which usually originate
      from the vestibular portion of the VIIIth cranial nerve. Treatment options
      include observation with serial imaging, stereotactic radiation and microsurgical
      removal. AIM: The goal of surgery was complete eradication of tumour with
      preservation of hearing and facial nerve function. METHODS: A retrospective
      review was undertaken of 24 cases of vestibular schwannoma jointly operated upon
      by a team of neurosurgeons and otologists at the Suez Canal University Hospital,
      with assessment of VIIth and VIIIth cranial nerve function, tumour size, and
      extent of growth. All surgery utilised a retromastoid, suboccipital approach.
      RESULTS: Complete tumour removal was achieved in 19 patients. Anatomical
      preservation of the facial nerve was possible in 66.6 per cent of patients. Pre
      operative, useful hearing was present in four patients, and preserved in 80 per
      cent. Cerebrospinal fluid leakage was diagnosed in two (8.3 per cent) patients,
      who responded to conservative therapy. CONCLUSION: The retromastoid, suboccipital
      surgical approach to the skull base can be safely and successfully achieved using
      a microsurgical technique, with minimal or no damage to neurovascular structures,
      even for large tumours.

PMID- 23552211
TI  - Syntactic generalization with novel intransitive verbs.
AB  - To understand how children develop adult argument structure, we must understand
      the nature of syntactic and semantic representations during development. The
      present studies compare the performance of children aged 2;6 on the two
      intransitive alternations in English: patient (Daddy is cooking the food/The food
      is cooking) and agent (Daddy is cooking). Children displayed abstract knowledge
      of both alternations, producing appropriate syntactic generalizations with novel
      verbs. These generalizations were adult-like in both flexibility and constraint.
      Rather than limiting their generalizations to lexicalized frames, children
      produced sentences with a variety of nouns and pronouns. They also avoided
      semantic overgeneralizations, producing intransitive sentences that respected the
      event restrictions and animacy cues. Some generated semantically appropriate
      agent intransitives when discourse pressure favored patient intransitives,
      indicating a stronger command of the first alternation. This was in line with
      frequency distributions in child-directed speech. These findings suggest that
      children have early access to representations that permit flexible argument
      structure generalization.

PMID- 23552212
TI  - Ethics of commercial screening tests.

PMID- 23552213
TI  - Subtle "supramolecular buttressing effects" in Cucurbit[7]uril/guest assemblies.
AB  - Biphenyl derivatives bearing a dimethylsulfonium group at position 3 and three
      different substituents at position 4 (H, F and CH3) have been prepared as probes
      to test the validity of the "supramolecular buttressing" concept. We define the
      latter as the alteration, by a neighboring unit, of a substituent effect on
      intermolecular recognition. In this case, the 4-substituents exert some pressure
      on the 3-dimethylsulfonium groups and control the ratio of their syn and anti
      conformations. As free species, biphenyls bearing 4-H and 4-F substituents are
      present as approximately equimolar mixtures of syn and anti-conformers, while the
      biphenyl scaffold with a 4-CH3 group adopts the anti-conformation exclusively.
      The 3-dimethylsulfonium substituents then interact with one of the carbonylated
      portals of Cucurbit[7]uril (CB[7]), and their conformations affect the position
      of the guests inside the cavity of the macrocycle, thereby validating our
      "supramolecular buttressing" model. Surprisingly however, binding affinities
      towards CB[7] are barely affected by the nature of the 4-substituents and the
      conformations of the neighboring sulfonium groups, despite very different
      electronic densities presented to the CB[7] portal in their syn or anti
      conformations. Solvation was found to dramatically smoothen host-guest Columbic
      interactions, although the latter remain important in the recognition process.
      Replacing the positively charged 3-dimethylsulfonium unit with an isopropyl
      substituent decreases the affinity of the biphenyl guest by 1000-fold.

PMID- 23552214
TI  - Evolution: Replication-transcription conflict promotes gene evolution.

PMID- 23552215
TI  - DNA repair: Search space.

PMID- 23552216
TI  - Gene regulation: In charge of translation.

PMID- 23552217
TI  - Gene expression: Extra X expression.

PMID- 23552218
TI  - Small RNAs: Defining piRNA expression.

PMID- 23552220
TI  - The anterior tooth development of cattle presented for slaughter: an analysis of
      age, sex and breed.
AB  - In a cross-sectional study, data from records of cattle slaughtered over a 1-year
      period at a large abattoir in South West England were analysed using an ordered
      category response model to investigate the inter-relationships between age, sex
      and breed on development of the permanent anterior (PA) teeth. Using the model,
      transition points at which there was a 50% probability of membership of each
      category of paired PA teeth were identified. Data from ~60,000 animals were
      initially analysed for age and sex effect. The age transition was found to be ~23
      months moving from zero to two teeth; 30 months for two to four teeth; 37 months
      for four to six teeth and 42 months for six to eight teeth. Males were found to
      develop, on average, ~22 days earlier than females across all stages. A reduced
      data set of ~23,000 animals registered as pure-bred only was used to compare
      breed and type interactions and to investigate sex effects within the sub
      categories. Breeds were grouped into dairy and beef-type and beef breeds split
      into native and continental. It was found that dairy-types moved through the
      transition points earlier than beef-types across all stages (interval varying
      between ~8 and 12 weeks) and that collectively, native beef breeds moved through
      the transition points by up to 3 weeks earlier than the continental beef breeds.
      Interestingly, in contrast to beef animals, dairy females matured before dairy
      males. However, the magnitude of the difference between dairy females and males
      diminished at the later stages of development. Differences were found between
      breeds. Across the first three stages, Ayrshires and Guernseys developed between
      3 and 6 weeks later than Friesian/Holsteins and Simmental, Limousin and Blonde
      Aquitaine 6 and 8 weeks later than Aberdeen Angus. Herefords, Charolais and South
      Devon developed later but by a smaller interval and Red Devon and Galloway showed
      the largest individual effect with transition delayed by 8 to 12 weeks.

PMID- 23552219
TI  - Functional and evolutionary implications of gene orthology.
AB  - Orthologues and paralogues are types of homologous genes that are related by
      speciation or duplication, respectively. Orthologous genes are generally assumed
      to retain equivalent functions in different organisms and to share other key
      properties. Several recent comparative genomic studies have focused on testing
      these expectations. Here we discuss the complexity of the evolution of gene
      phenotype relationships and assess the validity of the key implications of
      orthology and paralogy relationships as general statistical trends and guiding
      principles.

PMID- 23552221
TI  - Promoting critical perspectives in mental health nursing education.
AB  - This paper explores themes relevant to mental health nursing using the example of
      one educational module of a nursing degree. The authors argue that the
      educational preparation of mental health nursing students in higher education
      must address certain contested philosophical, conceptual, social and ethical
      dimensions of contemporary mental health care practice. These themes are
      discussed within the context of a third-year mental health nursing module within
      a Scottish nursing degree programme. By interlinking epistemology and ontology,
      the notion of student as 'critical practitioner', involving the encouragement of
      'critical thinking', is developed. This is shown via engagement with parallel
      perspectives of the sciences and the humanities in mental health. Narratives of
      student nurse engagement with selected literary texts demonstrate the extent to
      which issues of knowledge, self-awareness and personal development are central to
      a student's professional journey as they progress through an academic course. The
      paper concludes by suggesting that these 'critical perspectives' have important
      wider implications for curriculum design in nursing education. Insights from
      critical theory can equip nurse educators to challenge consumerist tendencies
      within contemporary higher education by encouraging them to remain knowledgeable,
      critical and ethically sensitive towards the needs of their students.

PMID- 23552222
TI  - A convenient light initiated synthesis of silver and gold nanoparticles using a
      single source precursor.
AB  - A photochemical approach is reported for the straightforward synthesis of silver
      and gold nanoparticles using a single source precursor under very mild
      conditions.

PMID- 23552223
TI  - Where bone meets implant: the characterization of nano-osseointegration.
AB  - The recent application of electron tomography to the study of biomaterial
      interfaces with bone has brought about an awareness of nano-osseointegration and,
      to a further extent, demanded increasingly advanced characterization
      methodologies. In this study, nanoscale osseointegration has been studied via
      laser-modified titanium implants. The micro- and nano-structured implants were
      placed in the proximal tibia of New Zealand white rabbits for six months. High
      resolution transmission electron microscopy (HRTEM), analytical microscopy,
      including energy dispersive X-ray spectroscopy (EDXS) and energy-filtered TEM
      (EFTEM), as well as electron tomography studies were used to investigate the
      degree of nano-osseointegration in two- and three-dimensions. HRTEM indicated the
      laser-modified surface encouraged the formation of crystalline hydroxyapatite in
      the immediate vicinity of the implant. Analytical studies suggested the presence
      of a functionally graded interface at the implant surface, characterized by the
      gradual intermixing of bone with oxide layer. Yet, the most compelling of
      techniques, which enabled straightforward visualization of nano-osseointegration,
      proved to be segmentation of electron tomographic reconstructions, where
      thresholding techniques identified bone penetrating into the nanoscale roughened
      surface features of laser-modified titanium. Combining high-resolution,
      analytical and three-dimensional electron microscopy techniques has proven to
      encourage identification and understanding of nano-osseointegration.

PMID- 23552224
TI  - Self-reported hypertension and use of antihypertensive medication among adults -
      United States, 2005-2009.
AB  - Hypertension affects one third of adults in the United States and is a major risk
      factor for heart disease and stroke. A previous report found differences in the
      prevalence of hypertension among racial/ethnic populations in the United States;
      blacks had a higher prevalence of hypertension, and Hispanics had the lowest use
      of antihypertensive medication. Recent variations in geographic differences in
      hypertension prevalence in the United States are less well known. To assess state
      level trends in self-reported hypertension and treatment among U.S. adults, CDC
      analyzed 2005-2009 data from the Behavioral Risk Factor Surveillance System
      (BRFSS). The results indicated wide variation among states in the prevalence of
      self-reported diagnosed hypertension and use of antihypertensive medications. In
      2009, the age-adjusted prevalence of self-reported hypertension ranged from 20.9%
      in Minnesota to 35.9% in Mississippi. The proportion reporting use of
      antihypertensive medications among those who reported hypertension ranged from
      52.3% in California to 74.1% in Tennessee. From 2005 to 2009, nearly all states
      had an increased prevalence of self-reported hypertension, with percentage-point
      increases ranging from 0.2 for Virginia (from 26.9% to 27.1%) to 7.0 for Kentucky
      (from 27.5% to 34.5%). Overall, from 2005 to 2009, the prevalence of self
      reported hypertension among U.S. adults increased from 25.8% to 28.3%. Among
      those reporting hypertension, the proportion using antihypertensive medications
      increased from 61.1% to 62.6%. Increased knowledge of the differences in self
      reported prevalence of hypertension and use of antihypertensive medications by
      state can help in guiding programs to prevent heart disease, stroke, and other
      complications of uncontrolled hypertension, including those conducted by state
      and local public health agencies and health-care providers.

PMID- 23552225
TI  - Blood lead levels in children aged 1-5 years - United States, 1999-2010.
AB  - The adverse health effects of lead exposure in children are well described and
      include intellectual and behavioral deficits, making lead exposure an important
      public health problem. No safe blood lead level (BLL) in children has been
      identified. To estimate the number of children aged 1-5 years in the United
      States at risk for adverse health effects from lead exposure and to assess the
      impact of prevention efforts, CDC analyzed data from the National Health and
      Nutrition Examination Survey (NHANES) from the periods 1999-2002 to 2007-2010.
      This report summarizes the results of that analysis, which indicated that the
      percentage of children aged 1-5 years with BLLs at or above the upper reference
      interval value of 5 ug/dL calculated using the 2007-2010 NHANES cycle was 2.6%.
      Thus, an estimated 535,000 U.S. children aged 1-5 years had BLLs >=5 ug/dL based
      on the U.S. Census Bureau 2010 count of the number of children in this age group.
      Despite progress in reducing BLLs among children in this age group overall,
      differences between the mean BLLs of different racial/ethnic and income groups
      persist, and work remains to be done to reach the Healthy People 2020 objective
      of reducing mean BLLs for all children in the United States (EH-8.2).

PMID- 23552226
TI  - Vital signs: Repeat births among teens - United States, 2007-2010.
AB  - BACKGROUND: Teen childbearing has potential negative health, economic, and social
      consequences for mother and child. Repeat teen childbearing further constrains
      the mother's education and employment possibilities. Rates of preterm and low
      birth weight are higher in teens with a repeat birth, compared with first births.
      METHODS: To assess patterns of repeat childbearing and postpartum contraceptive
      use among teens, CDC analyzed natality data from the National Vital Statistics
      System (NVSS) and the Pregnancy Risk Assessment Monitoring System (PRAMS) from
      2007-2010. RESULTS: Based on 2010 NVSS data from all 50 states and the District
      of Columbia, of more than 367,000 births to teens aged 15-19 years, 18.3% were
      repeat births. The percentage of teen births that represented repeat births
      decreased by 6.2% between 2007 and 2010. Disparities in repeat teen births exist
      by race/ethnicity, with the highest percentages found among American
      Indian/Alaska Natives (21.6%), Hispanics (20.9%), and non-Hispanic blacks (20.4%)
      and lowest among non-Hispanic whites (14.8%). Wide geographic disparities in the
      percentage of teen births that were repeat births also exist, ranging from 22% in
      Texas to 10% in New Hampshire. PRAMS data from 16 reporting areas (15 states and
      New York City) indicate that 91.2% of teen mothers used a contraceptive method 2
      6 months after giving birth, but only 22.4% of teen mothers used the most
      effective methods. Teens with a previous live birth were significantly more
      likely to use the most effective methods postpartum compared with those with no
      prior live birth (29.6% versus 20.9%, respectively). Non-Hispanic white and
      Hispanic teens were significantly more likely to use the most effective methods
      than non-Hispanic black teens (24.6% and 27.9% versus 14.3%, respectively). The
      percentage of teens reporting postpartum use of the most effective methods varied
      greatly geographically across the PRAMS reporting areas, ranging from 50.3% in
      Colorado to 7.2% in New York State. CONCLUSIONS: Although the prevalence of
      repeat teen birth has declined in recent years, nearly one in five teen births is
      a repeat birth. Large disparities exist in repeat teen births and use of the most
      effective contraceptive methods postpartum, which was reported by fewer than one
      out of four teen mothers. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Evidence-based
      approaches are needed to reduce repeat teen childbearing. These include linking
      pregnant and parenting teens to home visiting and similar programs that address a
      broad range of needs, and offering postpartum contraception to teens, including
      long-acting methods of reversible contraception.

PMID- 23552227
TI  - Protonation equilibrium of the poly(allylammonium) cation in an aqueous solution
      of binary 1:1 electrolytes.
AB  - The (de)protonation equilibrium of the poly(allylammonium) cation (PAH) in an
      aqueous solution of various binary 1:1 electrolytes of different concentrations
      (0.1 <= c(NaX)/mol dm(-3) <= 1.0; X = Cl(-), Br(-), I(-), NO3(-)) was
      investigated potentiometrically at 25  degrees C. The mixed and concentration
      apparent equilibrium deprotonation constants (Kap) were calculated from the
      experimentally collected data and concentration profiles of dissociated and
      undissociated functional groups were obtained. The standard pK value of monomers
      was estimated by extrapolating the pKap values determined at various
      concentrations of added electrolyte to the degree of dissociation alpha = 1. The
      dependence of pKap on the degree of dissociation could be well described by the
      two parameter model according to Mandel. The variation of pKap* with monomer
      dissociation degree was found to be in satisfactory agreement with the cylinder
      Stern model, based on the Poisson-Boltzmann (PB) equation, and a constant Stern
      capacitance. Generally, the derived apparent constants showed a pronounced
      dependence on the concentration of binary electrolytes and a weak dependence on
      the type of anion counterbalancing the polyion charge. The influence of the PAH
      chain length (polymers containing on average 150 and 700 monomers were examined)
      on the protonation equilibrium of PAH could not be observed.

PMID- 23552228
TI  - A review of greywater characteristics and treatment processes.
AB  - This paper presents a comprehensive literature review of different
      characteristics of greywater (GW) and current treatment methods. GW is domestic
      wastewater excluding toilet waste and can be classified as either low-load GW
      (excluding kitchen and laundry GW) or high-load GW (including kitchen and/or
      laundry). This review provides information on the quantity of GW produced, its
      constituents (macro and micro), existing guidelines for wastewater reuse, current
      treatment methods (from storage to disinfection) as well as related costs and
      environmental impacts. Moreover some successful examples from various countries
      around the world are examined. The current preferred treatments for GW use
      physical and biological/natural systems. Recently, chemical systems like
      coagulation, adsorption and advanced oxidation processes (AOPs) have been
      considered and have been successful for low to moderate strength GW. The presence
      of xenobiotic organic compounds (XOC), which are hazardous micropollutants in GW,
      is emphasised. Since conventional treatments are not efficient at removing XOC,
      it is recommended that future studies look at chemical treatment, especially AOPs
      that have been found to be successful at mineralising recalcitrant organic
      compounds in wastewater.

PMID- 23552229
TI  - Autotrophic nitrogen removal after ureolytic phosphate precipitation to remove
      both endogenous and exogenous nitrogen.
AB  - Anaerobic digestion yields effluents rich in ammonium and phosphate and poor in
      biodegradable organic carbon, thereby making them less suitable for conventional
      biological nitrogen and phosphorus removal. In addition, the demand for
      fertilizers is increasing, energy prices are rising and global phosphate reserves
      are declining. This requires both changes in wastewater treatment technologies
      and implementation of new processes. In this contribution a description is given
      of the combination of a ureolytic phosphate precipitation (UPP) and an
      autotrophic nitrogen removal (ANR) process on the anaerobic effluent of a potato
      processing company. The results obtained show that it is possible to recover
      phosphate as struvite and to remove the nitrogen with the ANR process. The ANR
      process was performed in either one or two reactors (partial nitritation +
      Anammox). The one-reactor configuration operated stably when the dissolved oxygen
      was kept between 0.1 and 0.35 mg L(-1). The best results for the two-reactor
      system were obtained when part of the effluent of the UPP was fully nitrified in
      a nitritation reactor and mixed in a 3:5 volumetric ratio with untreated ammonium
      containing effluent. A phosphate and nitrogen removal efficiency of respectively
      83 +/- 1% and of 86 +/- 7% was observed during this experiment.

PMID- 23552230
TI  - Degradation of phenol by using magnetic photocatalysts of titania.
AB  - Magnetic TiO2 (MT) composites were prepared and applied to degrading phenol,
      which is one of the listed priority pollutants. The effects of heat treatment
      under preparation on the photocatalytic activity of MT composites have been
      investigated by varying the soaking time under a constant final temperature of
      823 K. The total organic carbon and ring-remaining intermediates of o-DHB, p-DHB
      and 1,4-BQ in solution were detected during the photodegradation of phenol. All
      the resulting MT composites were the single-phase anatase and magnetite judged by
      X-ray diffraction patterns. The calcination of the as-prepared particles was
      proven to be extremely crucial to the photocatalytic activity. The best condition
      of heat treatment was found to be soaking time of 2 h at T = 823 K due to the
      good performance of photocatalytic activity, stable magnetic property, and
      reusability over three times. The results lead to the conclusion that recyclable
      MT composites prepared in this study, which belonged to the category of
      recyclable green materials, exhibit good photocatalytic activity to degrade
      phenol so as to possess applicable potential for the degradation of refractory
      organics in the aqueous solution. Furthermore, the environmental and health
      impacts were reduced as MT composites were applied in the treatment of water
      pollution.

PMID- 23552231
TI  - A mathematical approach to find long-term strategies for the implementation of
      resource-orientated sanitation.
AB  - In the present discussion of sustainability centralised water infrastructures are
      exposed to new challenges, which may cause a conceptual alteration in urban water
      management. If technologies for closing urban water and nutrient cycles are to at
      least partially replace existing systems, then intensive reconstruction work
      becomes essential. The paper presents the development and implementation of a
      mathematical approach to minimise environmental impact and economic costs on the
      way to more source-controlled future states in urban water management. To find an
      optimal transformation strategy, a simultaneous project scheduling and network
      flow problem was defined as a bi-criteria mixed-integer program. An optimal
      solution is found by minimising two objective functions concurrently - the
      economic costs and 'ecologic costs' for the period of consideration. This paper
      discusses the influence of the weighting of these two costs on optimal
      transformation strategies for a real catchment in Germany. The results show that
      the approach can very well support decision makers when showing all impacts of
      transformation processes in detail. All in all, the developed model can be seen
      as a first step in strategy-finding for transformations in existing urban water
      systems.

PMID- 23552232
TI  - Impact of the As Samra wastewater treatment plant upgrade on the water quality
      (COD, electrical conductivity, TP, TN) of the Zarqa River.
AB  - The impact of the As Samra wastewater treatment plant upgrade on the quality of
      the Zarqa River (ZR) water was investigated. Time series data that extend from
      October 2005 until December 2009 obtained by a state-of-the-art telemetric
      monitoring system were analyzed at two monitoring stations located 4 to 5 km
      downstream of the As Samra effluent confluence with the Zarqa River and about 25
      km further downstream. Time series data that represent the ZR water quality
      before and after the As Samra upgrade were analyzed for chemical oxygen demand
      (COD), electrical conductivity (EC), total phosphorus (TP) and total nitrogen
      (TN). The means of the monitored parameters, before and after the As Samra
      upgrade, showed that the reductions in the COD, TP and TN were statistically
      significant, while no reduction in the EC was observed. Comparing the selected
      parameters with the Jordanian standards for reclaimed wastewater reuse in
      irrigation and with the Ayers & Westcot guidelines for interpretation of water
      quality for irrigation showed that the ZR water has improved towards meeting the
      required standards and guidelines for treated wastewater reuse in irrigation.

PMID- 23552233
TI  - Environmental and economic assessment of municipal sewage sludge management - a
      case study in Beijing, China.
AB  - A case study was conducted in Beijing to identify municipal sewage sludge (SS)
      management systems appropriate for a sound material-cycle society. The
      environmental and economic impacts of four realistic SS-handling scenarios were
      investigated: stabilization by thermal drying, increased inclusion of SS in
      cement manufacture, and using either dried or carbonized SS as substitute fuel
      for coal-fired power generation plants. The results showed that the current
      sludge management system had the lowest operating cost but higher greenhouse gas
      (GHG) emissions and a low recycling rate. The case with the use of carbonized SS
      reused in coal-fired power plants had higher energy consumption and almost the
      same GHG emissions as the current system. On the other hand, the case including
      more SS in cement manufacture had the same level of energy consumption with much
      lower GHG emissions. The case with the use of dried SS in coal-fired power plants
      also resulted in lower energy consumption and lower GHG emissions than at
      present. Furthermore, sensitivity analysis showed that drying SS with surplus
      heat from cement plants used less energy and emitted less GHG compared to the
      other two drying methods.

PMID- 23552234
TI  - Enlightenment from ancient Chinese urban and rural stormwater management
      practices.
AB  - Hundreds of years ago, the ancient Chinese implemented several outstanding
      projects to cope with the changing climate and violent floods. Some of these
      projects are still in use today. These projects evolved from the experience and
      knowledge accumulated through the long coexistence of people with nature. The
      concepts behind these ancient stormwater management practices, such as low-impact
      development and sustainable drainage systems, are similar to the technology
      applied in modern stormwater management. This paper presents the cases of the
      Hani Terrace in Yunnan and the Fushou drainage system of Ganzhou in Jiangxi. The
      ancient Chinese knowledge behind these cases is seen in the design concepts and
      the features of these projects. These features help us to understand better their
      applications in the contemporary environment. In today's more complex
      environment, integrating traditional and advanced philosophy with modern
      technologies is extremely useful in building urban and rural stormwater
      management systems in China.

PMID- 23552235
TI  - Biological Nutrient Removal Model No. 2 (BNRM2): a general model for wastewater
      treatment plants.
AB  - This paper presents the plant-wide model Biological Nutrient Removal Model No. 2
      (BNRM2). Since nitrite was not considered in the BNRM1, and this previous model
      also failed to accurately simulate the anaerobic digestion because precipitation
      processes were not considered, an extension of BNRM1 has been developed. This
      extension comprises all the components and processes required to simulate
      nitrogen removal via nitrite and the formation of the solids most likely to
      precipitate in anaerobic digesters. The solids considered in BNRM2 are: struvite,
      amorphous calcium phosphate, hidroxyapatite, newberite, vivianite, strengite,
      variscite, and calcium carbonate. With regard to nitrogen removal via nitrite,
      apart from nitrite oxidizing bacteria two groups of ammonium oxidizing organisms
      (AOO) have been considered since different sets of kinetic parameters have been
      reported for the AOO present in activated sludge systems and SHARON (Single
      reactor system for High activity Ammonium Removal Over Nitrite) reactors. Due to
      the new processes considered, BNRM2 allows an accurate prediction of wastewater
      treatment plant performance in wider environmental and operating conditions.

PMID- 23552236
TI  - Adsorption removal of tetracycline from aqueous solution by anaerobic granular
      sludge: equilibrium and kinetic studies.
AB  - High concentration animal wastewater is often contaminated by tetracycline and an
      upflow anaerobic sludge bioreactor (UASB) with granular sludge is often used to
      treat the wastewater. The investigation of the adsorption process of tetracycline
      on anaerobic granular sludge during anaerobic digestion of animal wastewater will
      increase the understanding of antibiotics behavior in the UASB reactor. In this
      study, the effects of initial pH, humic acid concentration, and temperature on
      the removal of tetracycline by anaerobic granular sludge from aqueous solution
      were investigated using the batch adsorption technique in 100 mL flasks with 75
      mL of work volume. The results show that the highest removal efficiency of 93.0%
      was achieved around pH 3.0 and the removal efficiency at the neutral pH range (pH
      6.0-8.0) is about 91.5%. The thermodynamic analysis indicates that the adsorption
      is a spontaneous and endothermic process. The adsorption kinetics followed the
      pseudo-second-order equation. The adsorption isotherms analysis indicates that
      the Langmuir model is better than the Freundlich model for the description of the
      adsorption process and confirms the result of thermodynamics analysis. The
      maximum adsorption capacities were 2.984, 4.108 and 4.618 mg/g at 25, 35 and 45 
      degrees C, respectively. These results provide useful information for
      understanding the fate and transformation of tetracycline in a UASB digestion
      system and improving the management of tetracycline contaminated animal
      wastewater.

PMID- 23552237
TI  - Application of ultrasound and air stripping for the removal of aromatic
      hydrocarbons from spent sulfidic caustic for use in autotrophic denitrification
      as an electron donor.
AB  - Spent sulfidic caustic (SSC) produced from petroleum industry can be reused to
      denitrify nitrate-nitrogen via a biological nitrogen removal process as an
      electron donor for sulfur-based autotrophic denitrification, because it has a
      large amount of dissolved sulfur. However, SSC has to be refined because it also
      contains some aromatic hydrocarbons, typically benzene, toluene, ethylbenzene,
      xylene (BTEX) and phenol that are recalcitrant organic compounds. In this study,
      laboratory-scale ultrasound irradiation and air stripping treatment were applied
      in order to remove these aromatic hydrocarbons. In the ultrasound system, both
      BTEX and phenol were exponentially removed by ultrasound irradiation during 60
      min of reaction time to give the greatest removal efficiency of about 80%.
      Whereas, about 95% removal efficiency of BTEX was achieved, but not any
      significant phenol removal, within 30 min in the air stripping system, indicating
      that air stripping was a more efficient method than ultrasound irradiation.
      However, since air stripping did not remove any significant phenol, an additional
      process for degrading phenol was required. Accordingly, we applied a combined
      ultrasound and air stripping process. In these experiments, the removal
      efficiencies of BTEX and phenol were improved compared to the application of
      ultrasound and air stripping alone. Thus, the combined ultrasound and air
      stripping treatment is appropriate for refining SSC.

PMID- 23552238
TI  - Assessing and monitoring agroenvironmental determinants of recreational
      freshwater quality using remote sensing.
AB  - Diverse fecal and nonfecal bacterial contamination and nutrient sources (e.g.
      agriculture, human activities and wildlife) represent a considerable non-point
      source load entering natural recreational waters which may adversely affect water
      quality. Monitoring of natural recreational water microbial quality is most often
      based mainly on testing a set of microbiological indicators. The cost and labour
      involved in testing numerous water samples may be significant when a large number
      of sites must be monitored repetitively over time. In addition to water testing,
      ongoing monitoring of key environmental factors known to influence microbial
      contamination may be carried out as an additional component. Monitoring of
      environmental factors can now be performed using remote sensing technology which
      represents an increasingly recognized source of rigorous and recurrent data,
      especially when monitoring over a large or difficult to access territory is
      needed. To determine whether this technology could be useful in the context of
      recreational water monitoring, we evaluated a set of agroenvironmental
      determinants associated with fecal contamination of recreational waters through a
      multivariable logistic regression model built with data extracted from satellite
      imagery. We found that variables describing the proportions of land with
      agricultural and impervious surfaces, as derived from remote sensing
      observations, were statistically associated (odds ratio, OR = 11 and 5.2,
      respectively) with a higher level of fecal coliforms in lake waters in the
      southwestern region of Quebec, Canada. From a technical perspective, remote
      sensing may provide important added-value in the monitoring of microbial risk
      from recreational waters and further applications of this technology should be
      investigated to support public health risk assessments and environmental
      monitoring programs relating to water quality.

PMID- 23552239
TI  - Pathogenic parasites and enteroviruses in wastewater: support for a regulation on
      water reuse.
AB  - Brazilian regulations for nonpotable reuse are being established using World
      Health Organization guidelines, however, they should be developed based on local
      monitoring studies. This study intended to analyze enteroviruses, protozoa and
      viable Ascaris sp. eggs in raw (24) and treated (24) effluents from four
      Wastewater Treatment Plants of Sao Paulo State, Brazil. The protozoa were
      detected with the US Environmental Protection Agency (USEPA) Method 1623 in the
      treated effluents and by centrifugation/Immunomagnetic Separation in the raw
      influent samples. Viable Ascaris sp. eggs were analyzed according to a modified
      USEPA method. Enteroviruses were quantified by using human rhabdomyosarcoma cells
      after adequate concentration procedures. All wastewater influents were positive
      for Giardia sp. whereas Cryptosporidium sp. was detected in 58.3% of the samples.
      Giardia sp. and Cryptosporidium sp. were present in 79.2 and 25.0% respectively,
      of the treated wastewater samples. Viable Ascaris sp. eggs were detected in 50.0
      and 12.5% of influent and treated wastewater samples. Enteroviruses were isolated
      in the 24 raw influent samples and in 46% of the treated samples. Taking into
      account the densities of Giardia sp. in some treated wastewaters intended to be
      used as reclaimed water, Quantitative Microbial Risk Assessment studies should be
      conducted to establish pathogen quantitative criteria for a future Brazilian
      regulation for water reuse.

PMID- 23552241
TI  - Integrating water resources management in eco-hydrological modelling.
AB  - In this paper the integration of water resources management with regard to
      reservoir management in an eco-hydrological model is described. The model was
      designed to simulate different reservoir management options, such as optimized
      hydropower production, irrigation intake from the reservoir or optimized
      provisioning downstream. The integrated model can be used to investigate the
      impacts of climate variability/change on discharge or to study possible
      adaptation strategies in terms of reservoir management. The study area, the Upper
      Niger Basin located in the West African Sahel, is characterized by a monsoon-type
      climate. Rainfall and discharge regime are subject to strong seasonality.
      Measured data from a reservoir are used to show that the reservoir model and the
      integrated management options can be used to simulate the regulation of this
      reservoir. The inflow into the reservoir and the discharge downstream of the
      reservoir are quite distinctive, which points out the importance of the inclusion
      of water resources management.

PMID- 23552240
TI  - Preparation and antibacterial property of PES/AgNO3 three-bore hollow fiber
      ultrafiltration membranes.
AB  - In this study, a three-bore polyethersulfone (PES) hollow fiber ultrafiltration
      (UF) membrane with antibacterial properties was prepared by phase inversion,
      using PES as the membrane material, N,N-dimethylacetamide (DMAC) as solvent,
      polyvinylpyrrolidone (PVP) and AgNO3 as additives. The silver particles were
      detected by X-ray photoelectron spectroscopy. The effect of AgNO3 content on the
      antibacterial properties and separation performance was studied in detail. The
      membranes showed good antibacterial activity against Escherichia coli after
      adding AgNO3 and the antibacterial rate of PES/AgNO3 UF membrane with AgNO3
      content of 1 wt% could reach 99.9% after running for 48 hours. Moreover, the
      bovine serum albumin solution filtration results indicated that the PES/AgNO3
      membranes had a certain degree of antifouling performance. Therefore, three-bore
      PES/AgNO3 membranes have a potential application to reduce both bacterial and
      organic fouling in water treatment.

PMID- 23552242
TI  - Pyrosequencing estimates of the diversity of antibiotic resistant bacteria in a
      wastewater system.
AB  - Standard protocols for monitoring wastewater treatment efficacy target
      Escherichia coli and fecal coliforms. This might not accurately describe risks
      associated with antibiotic resistance in the bacterial population of treated
      wastewaters. We modified a standard agar recovery method by amending it with
      various antibiotics. The resulting bacterial colonies were submitted to 454
      pyrosequencing; thus we identified the diversity of culturable antibiotic
      resistant bacteria from treated and raw wastewaters. This approach produced
      209,706 high quality reads of >300 bp. Operational taxonomic units (OTUs) within
      Proteobacteria dominated the system. The Shannon-Wiener H' index showed bacterial
      populations recovered on ciprofloxacin amended agars to be the least diverse.
      Principal component analysis of OTU distribution at phylum level showed that
      Proteobacteria accounted for most of the variability. The same analysis revealed
      most of the samples to have similar diversities at phylum level being dominated
      by Proteobacteria, though a few samples, typically recovered from ciprofloxacin
      or doxycycline amended agars were often dissimilar. Arcobacter spp. or E. coli
      were dominant in the bacterial communities recovered on agars amended with
      ciprofloxacin or doxycycline, respectively. Genera containing putative pathogens
      were mostly representatives of Gamma and Epsilon proteobacteria. Bacterial
      populations containing multiple antibiotic resistance (MAR) in the final treated
      effluent was a possibility.

PMID- 23552243
TI  - Application of 1-hydroxyethylidene-1, 1-diphosphonic acid in boiler water for
      industrial boilers.
AB  - The primary method used for boiler water treatment is the addition of chemicals
      to industrial boilers to prevent corrosion and scaling. The static scale
      inhibition method was used to evaluate the scale inhibition performance of 1
      hydroxyethylidene-1, 1-diphosphonic acid (HEDP). Autoclave static experiments
      were used to study the corrosion inhibition properties of the main material for
      industrial boilers (20# carbon steel) with an HEDP additive in the industrial
      boiler water medium. The electrochemical behavior of HEDP on carbon steel
      corrosion control was investigated using electrochemical impedance spectroscopy
      and Tafel polarization techniques. Experimental results indicate that HEDP can
      have a good scale inhibition effect when added at a quantity of 5 to 7 mg/L at a
      test temperature of not more than 100  degrees C. To achieve a high scale
      inhibition rate, the HEDP dosage must be increased when the test temperature
      exceeds 100  degrees C. Electrochemical and autoclave static experimental results
      suggest that HEDP has a good corrosion inhibition effect on 20# carbon steel at a
      concentration of 25 mg/L. HEDP is an excellent water treatment agent.

PMID- 23552244
TI  - Effect of wastewater chlorination on endocrine disruptor removal.
AB  - Endocrine disrupting chemicals (EDCs) are compounds of mainly anthropogenic
      origin that interfere with the endocrine system of animals and humans thus
      causing a series of disorders. Wastewater treatment plants are one of the major
      routes for transporting such chemicals to the water courses. In the context of
      this study, several chlorination batch tests were performed in order to assess
      the effectiveness of chlorination to remove bisphenol A (BPA), triclosan (TCS),
      nonylphenol (NP) and its ethoxylates (NP1EO and NP2EO) from secondary effluent.
      According to the results, an appreciable removal of NP, BPA and TCS to the order
      of 60-84% was observed as an effect of moderate chlorination doses. This was not
      the case for NP1EO and NP2EO as even at high chlorine doses, removal efficiencies
      were lower (37% for NP1EO and 52% for NP2EO). Removal efficiencies of NP, BPA and
      TCS are practically independent of contact time, although this was not the case
      for NP1EO and NP2EO. Based on toxicity experiments, it is anticipated that
      following chlorination of the target chemicals, production of more toxic
      metabolites is taking place. Therefore the effectiveness of chlorination to
      remove EDCs is questionable and more research is needed to guarantee safe
      wastewater reuse.

PMID- 23552245
TI  - The use of rotifers for limiting filamentous bacteria Type 021N, a bacteria
      causing activated sludge bulking.
AB  - The excessive growth of filamentous bacteria and the resultant bulking of
      activated sludge constitute a serious problem in numerous wastewater treatment
      plants. Lecane inermis rotifers were previously shown to be capable of reducing
      the abundance of Microthrix parvicella and Nostocoida limicola in activated
      sludge. In the present study, the effectiveness of four Lecane clones in reducing
      the abundance of Type 021N filamentous bacteria was investigated. Three
      independent experiments were carried out on activated sludge from three different
      treatment plants. We found that Lecane rotifers are efficient consumers of Type
      021N filaments.

PMID- 23552246
TI  - Dye tracers as a tool for outfall studies: dilution measurement approach.
AB  - Dye tracer technique is well established and of wide application for assessment
      of outfalls and for delineation of near field and far field extensions. Common
      goals of a tracer study include the measurement of the dilution factor,
      estimation of the dispersion coefficients, measurement of the effluent discharge
      and calibration of a contaminant transport model. This paper presents a brief
      review of the methods involving the use of dye tracer for outfall assessment and
      illustrates the methods of slug release and continuous injection based on two
      real cases of campaigns carried out on Brazilian coastal waters. Slug injection
      on the surface of the water body was used for preliminary dispersion studies
      aiming at outfall positioning. During the operational phase of an outfall, the
      continuous injection of dye tracer was used to determine effluent dilution in
      different seasons. In coastal waters of Rio de Janeiro city, sea current pattern,
      tidal modulation and thermal stratification explained the main features of the
      dilution field.

PMID- 23552247
TI  - Assessing the efficiency of different CSO positions based on network graph
      characteristics.
AB  - The technical design of urban drainage systems comprises two major aspects:
      first, the spatial layout of the sewer system and second, the pipe-sizing
      process. Usually, engineers determine the spatial layout of the sewer network
      manually, taking into account physical features and future planning scenarios.
      Before the pipe-sizing process starts, it is important to determine locations of
      possible weirs and combined sewer overflows (CSOs) based on, e.g. distance to
      receiving water bodies or to a wastewater treatment plant and available space for
      storage units. However, positions of CSOs are also determined by topological
      characteristics of the sewer networks. In order to better understand the impact
      of placement choices for CSOs and storage units in new systems, this work aims to
      determine case unspecific, general rules. Therefore, based on numerous,
      stochastically generated virtual alpine sewer systems of different sizes it is
      investigated how choices for placement of CSOs and storage units have an impact
      on the pipe-sizing process (hence, also on investment costs) and on technical
      performance (CSO efficiency and flooding). To describe the impact of the
      topological positions of these elements in the sewer networks, graph
      characteristics are used. With an evaluation of 2,000 different alpine combined
      sewer systems, it was found that, as expected, with CSOs at more downstream
      positions in the network, greater construction costs and better performance
      regarding CSO efficiency result. At a specific point (i.e. topological network
      position), no significant difference (further increase) in construction costs can
      be identified. Contrarily, the flooding efficiency increases with more upstream
      positions of the CSOs. Therefore, CSO and flooding efficiency are in a trade-off
      conflict and a compromise is required.

PMID- 23552248
TI  - Enhanced oil-mineral aggregation with modified bentonite.
AB  - The application of modified-bentonite-enhanced oil dispersion in water and oil
      mineral aggregate (OMA) formation was studied in the laboratory. The effect of
      modification on the surface properties of bentonite was characterized. The
      hydrophobicity and surface electric properties of bentonite were significantly
      improved by attaching cetyltrimethyl ammonium bromide to its surface. The results
      showed that surface properties of bentonite played an important role in OMA
      formation. Spherical droplets of OMAs were formed with natural bentonite and
      elongated solid OMAs and flake OMAs were formed with modified bentonite as
      observed by fluorescence microscopy. The effects of shaking time, oil
      concentration and mineral content were also studied. It was suggested that oil
      concentration and mineral content were critical factors and OMA formed rapidly
      with both types of bentonite. Modified bentonite had better performance on OMA
      formation than hydrophilic natural bentonite.

PMID- 23552249
TI  - Multi-stage constructed wetland systems for municipal wastewater treatment.
AB  - In the present paper the detailed design and performances of two municipal
      wastewater treatment plants, a four-stage constructed wetlands (CW) system
      located in the city of Dicomano (about 3,500 inhabitants) in Italy, and a three
      stage CW system for the village of Chorfech (about 500 inhabitants) in Tunisia,
      are presented. The obtained results demonstrate that multi-stage CWs provide an
      excellent secondary treatment for wastewaters with variable operative conditions,
      reaching also an appropriate effluent quality for reuse. Dicomano CWs have shown
      good performances, on average 86% of removal for the Organic Load, 60% for Total
      Nitrogen (TN), 43% for Total Phosphorus (TP), 89% for Total Suspended Solids
      (TSS) and 76% for Ammonium (NH4(+)). Even the disinfection process has performed
      in a very satisfactory way, reaching up to 4-5 logs of reduction of the inlet
      pathogens concentration, with an Escherichia coli average concentration in the
      outlet often below 200 UFC/100 mL. The mean overall removal rates of the Chorfech
      CWs during the monitored period have been, respectively, equal to 97% for TSS and
      Biochemical Oxygen Demand (BOD5), 95% for Chemical Oxygen Demand (COD), 71% for
      TN and 82% for TP. The observed removal of E. coli by the CW system was in this
      case 2.5 log units.

PMID- 23552250
TI  - Study of environmental risks incurred by leakage of lithium cells to the food
      chain in a freshwater ecosystem.
AB  - Water flea (Daphnia magna) and fish (Carassius auratus) at trophic level were
      used for comprehensive evaluation of environmental risks incurred by manufactured
      nanomaterial (nNi(OH)2) as leaked from lithium cells to the food chain in
      freshwater ecosystem. The 48, 72 and 96 h acute toxicities of water suspensions
      of nNi(OH)2 to the flea and the fish were tested, using the immobilization and
      the mortality as toxicological endpoints. The results showed that the water flea
      was more highly sensitive to nNi(OH)2 than the fish. Then, the fish were exposed
      to 1.0 mg/L nNi(OH)2 for 6, 12, 24, 36, 48, 60, 72 and 96 h, and the relationship
      between the concentrations in the water and the fish were described by a
      bioconcentration factor (BCF). After calculation, lgBCF is 1.61. Reactive oxygen
      species (ROS) generation was studied after fish were exposed to 1.0 mg/L water
      suspensions of nNi(OH)2 for 24 h. As proved by electron paramagnetic resonance,
      nNi(OH)2 may induce the generation of hydroxyl radical in the fish, and nNi(OH)2
      as concentrated in the fish may incur redox reaction and produce redox metabolic
      intermediates. As one of the important toxic mechanisms of nNi(OH)2 to the fish,
      the oxidative stress mechanism requires further study.

PMID- 23552251
TI  - Photodegradation of amoxicillin in aqueous solution under simulated irradiation:
      influencing factors and mechanisms.
AB  - This paper investigated the effects of selected common chemical species in
      natural waters (HCO3(-), NO3(-) and humic acids (HA)) on the photodegradation of
      amoxicillin (AMO) under simulated irradiation using a 300 W xenon lamp. Quenching
      experiments were carried out to explore the mechanisms of AMO photodegradation.
      The results indicated that AMO photodegradation followed pseudo-first-order
      kinetics. Increasing AMO concentration from 100 to 1,000 MUg L(-1) led to the
      decrease in the photodegradation rate constant from 0.2411 to 0.1912 min(-1). The
      presence of NO3(-) and HA obviously inhibited the photodegradation rate of AMO
      because they can compete for photons with AMO. Bicarbonate, as a hydroxyl radical
      (.OH) scavenger, also adversely affected AMO photodegradation. Quenching
      experiments in pure water suggested that AMO could undergo self-sensitized
      photooxidation via .OH and singlet oxygen ((1)O2), accounting for AMO removal of
      34.86 and 8.26%, respectively. In HA solutions, the indirect photodegradation of
      AMO was mostly attributed to the produced .OH (22.37%), (1)O2 (24.12%) and (3)HA*
      (20.80%), whereas the contribution of direct photodegradation was to some extent
      decreased.

PMID- 23552252
TI  - Modeling of heavy metals removal from aqueous solution using activated carbon
      produced from cotton stalk.
AB  - Activated carbon produced from cotton stalks was examined for the removal of
      heavy metal contaminants. Adsorption studies in completely mixed batch reactors
      were used to generate equilibrium pH adsorption edges. Continuous flow
      experiments using the activated carbon in fixed beds were conducted to determine
      heavy metal breakthrough versus bed volumes treated. At given pH value in the
      range 5-7, the adsorption capacity was similar for copper and lead and clearly
      greater than for cadmium. A surface titration experiment indicated negative
      surface charge of the activated carbon at pH > 6, meaning that electrostatic
      attraction of the divalent heavy metals can occur below the pH required for
      precipitation. Substantive metal removal below the pH of zero charge might be due
      to surface complexation. Accordingly, a surface complexation model approach that
      utilizes an electrostatic term in the double-layer description was used to
      estimate equilibrium constants for the protolysis interactions of the activated
      carbon surface as well as equilibria between background ions used to establish
      ionic strength and the sorbent surface. Pb(II) adsorption edges were best modeled
      using inner-layer surface complexation of Pb(2+), while Cd(II) and Cu(II) data
      were best fit by outer-layer complexes with Me(2+). The full set of equilibrium
      constants were used as input in a dual-rate dynamic model to simulate the
      breakthrough curves of the target metals (Pb, Cu and Cd) from fixed bed
      experiments and to estimate external (or film) diffusion and internal (surface)
      diffusion coefficients.

PMID- 23552253
TI  - Removal of aniline and phenol from water using raw and aluminum hydroxide
      modified diatomite.
AB  - The feasibility of using raw diatomite and aluminum hydroxide-modified diatomite
      (Al-diatomite) for removal of aniline and phenol from water was investigated.
      Their physicochemical characteristics such as pHsolution, point of zero charge
      (pHPZC), surface area, Fourier transform infrared (FT-IR) and scanning electron
      microscopy was determined. After the raw diatomite was modified, the surface area
      of Al-diatomite increases from 26.67 to 82.65 m(2) g(-1). The pHPZC and
      pHsolution (10%) occurred around pH 5.2 and pH 8.6, respectively. The removal
      rates of aniline and phenol on diatomite and Al-diatomite decreased with
      increasing solution pH, while surface charge density decreased. The adsorption of
      aniline and phenol on diatomite presented a good fit to the Langmuir and
      Freundlich models, but the models are not fit to forecast the adsorption of
      aniline and phenol on Al-diatomite. The study indicated that electrostatic
      interaction was a dominating mechanism of aniline and phenol sorption onto Al
      diatomite.

PMID- 23552254
TI  - Rapid cultivation of aerobic granular sludge by bone glue augmentation and
      contaminant removal characteristics.
AB  - To achieve a quick start-up and stable operation, aerobic granular sludge (AGS)
      was cultivated in a sequencing batch airlift reactor (SBAR) with the addition of
      bone glue augmentation. Adding an amount of bone glue (40 mg L(-1)) can
      accelerate granulation, which advanced by 10 d on average. Aerobic granules of
      size 0.5-3.0 mm were dominant in the SBAR and the settling velocity acquired a
      better correlation with the size of the AGS. In addition, the content of total
      polysaccharides was 19.54 mg gMLSS(-1) (grams of mixed liquor suspended solids)
      (an increase of 34.0%), the content of total protein was 60.59 mg gMLSS(-1) (an
      increase of a factor of 33) and the total proteins/total polysaccharides ratio
      was 3.3. The relatively high protein content was an essential feature for
      cultivation of AGS, which may indicate that extracellular polymeric substance was
      the mechanism for granulation due to the adhesion of microorganisms by bone glue.
      AGS possessed better chemical oxygen demand, NH4(+)-N and PO4(3-)-P removal
      efficiency (of 86.7, 90.6 and 93.8%, respectively) and no nitrite accumulation
      was observed in the whole process.

PMID- 23552255
TI  - A stochastic optimization approach for integrated urban water resource planning.
AB  - Urban water is facing the challenges of both scarcity and water quality
      deterioration. Consideration of nonconventional water resources has increasingly
      become essential over the last decade in urban water resource planning. In
      addition, rapid urbanization and economic development has led to an increasing
      uncertain water demand and fragile water infrastructures. Planning of urban water
      resources is thus in need of not only an integrated consideration of both
      conventional and nonconventional urban water resources including reclaimed
      wastewater and harvested rainwater, but also the ability to design under gross
      future uncertainties for better reliability. This paper developed an integrated
      nonlinear stochastic optimization model for urban water resource evaluation and
      planning in order to optimize urban water flows. It accounted for not only water
      quantity but also water quality from different sources and for different uses
      with different costs. The model successfully applied to a case study in Beijing,
      which is facing a significant water shortage. The results reveal how various
      urban water resources could be cost-effectively allocated by different planning
      alternatives and how their reliabilities would change.

PMID- 23552256
TI  - Synthesis of kaolinite/iron oxide magnetic composites and their use in the
      removal of Cd(II) from aqueous solutions.
AB  - Kaolinite/iron oxide magnetic composites (kaolinite/MCs) were used as adsorbent
      for the removal of Cd(II) from aqueous solutions. The influences of pH, ionic
      strength, solid/liquid ratio and temperature on Cd(II) sorption on kaolinite/MCs
      were evaluated. The results showed that the removal of Cd(II) on kaolinite/MCs
      was strongly dependent on pH and ionic strength. An optimal kaolinite/MCs
      concentration mass per volume for removal of Cd(II) from aqueous solutions was
      1.4 g L(-1). The Langmuir and Freundlich models were used to simulate sorption
      isotherms of Cd(II) at three different temperatures of 293, 313 and 333 K. The
      sorption of Cd(II) on kaolinite/MCs increased with increasing temperature, and
      thermodynamic parameters (standard entropy change, enthalpy change and Gibbs free
      energy change) illustrated that this sorption process was spontaneous and
      endothermic. The sorption behaviors of Cd(II) were mainly dependent on surface
      properties of kaolinite/MCs and solution chemistry conditions. The sorption
      capacity of Cd(II) on kaolinite/MCs was lower than that on kaolinite, because
      iron oxide particles decreased surface charge of kaolinite leading to less
      sorption capacity. Due to high magnetism, kaolinite/MCs could be easily separated
      with an external magnetic field. Kaolinite/MCs could therefore be used as
      potential adsorbent for preconcentration and immobilization of Cd(II) ions from
      large volumes of aqueous solutions.

PMID- 23552257
TI  - Digging into the extracellular matrix of a complex microbial community using a
      combined metagenomic and metaproteomic approach.
AB  - Knowledge about identity and function of extracellular polymeric substances (EPS)
      in complex microbial communities is sparse, although these components have a
      large influence on the function of the microbial communities. We investigated the
      presence of selected genes potentially involved in EPS production in a 145 Mbp
      metagenome prepared by Illumina sequencing from a full-scale wastewater treatment
      plant carrying out enhanced biological phosphorus removal (EBPR). A range of
      genes involved in alginate production was identified and assigned mainly to
      bacteria from the phylum Bacteroidetes. Furthermore, several proteins in the EPS
      matrix were extracted, purified and identified by mass spectrometry. By using the
      metagenome as a reference for the metaproteomic analysis, more proteins were
      identified compared to using only publicly available databases. This illustrates
      the low degree of similarity between the bacteria in the EBPR community and the
      sequenced bacteria in the public databases. Hence, the combination of
      metagenomics and metaproteomics presented here is needed to investigate the
      identity of the proteins in the EPS matrix.

PMID- 23552259
TI  - Surface lattice dynamics and electron-phonon interaction in ultrathin Bi(111)
      film.
AB  - The surface phonon and electron-phonon interactions in the two-dimensional
      topological insulator Bi(111) film are calculated, including the spin-orbit
      coupling from density-functional perturbation theory. By analyzing the zone
      center phonons, an anomalous phonon hardening of two Raman modes, Eg and A1g, in
      ultrathin films is found and is explained by considering the redistribution of
      the charge density on the surface of the semimetallic Bi. Surface phonon band
      structures and the surface phonon density of states are given, and we find that
      softening and hardening of surface phonon modes occur simultaneously in ultrathin
      Bi film, but the softening may dominate over the hardening. The calculated
      electron-phonon coupling constant lambda for Bi(111) film is much larger than
      that for the bulk, which might induce surface-localized superconductivity in this
      two-dimensional topological insulator.

PMID- 23552258
TI  - Access to subspecialty care for patients with mobility impairment: a survey.
AB  - BACKGROUND: Adults who use wheelchairs have difficulty accessing physicians and
      receive less preventive care than their able-bodied counterparts. OBJECTIVE: To
      learn about the accessibility of medical and surgical subspecialist practices for
      patients with mobility impairment. DESIGN: A telephone survey was used to try to
      make an appointment for a fictional patient who was obese and hemiparetic, used a
      wheelchair, and could not self-transfer from chair to examination table. SETTING:
      256 endocrinology, gynecology, orthopedic surgery, rheumatology, urology,
      ophthalmology, otolaryngology, and psychiatry practices in 4 U.S. cities.
      PATIENTS: None. MEASUREMENTS: Accessibility of the practice, reasons for lack of
      accessibility, and planned method of transfer of the patient to an examination
      table. RESULTS: Of 256 practices, 56 (22%) reported that they could not
      accommodate the patient, 9 (4%) reported that the building was inaccessible, 47
      (18%) reported inability to transfer a patient from a wheelchair to an
      examination table, and 22 (9%) reported use of height-adjustable tables or a lift
      for transfer. Gynecology was the subspecialty with the highest rate of
      inaccessible practices (44%). LIMITATION: Small numbers of practices in 8
      subspecialties in 4 cities and use of a fictional patient with obesity and
      hemiparesis limit generalizability. CONCLUSION: Many subspecialists could not
      accommodate a patient with mobility impairment because they could not transfer
      the patient to an examination table. Better awareness among providers about the
      requirements of the Americans with Disabilities Act and the standards of care for
      patients in wheelchairs is needed. PRIMARY FUNDING SOURCE: None.

PMID- 23552260
TI  - Histological, ultrastructural and immunohistochemical studies on the protective
      effect of ginger extract against cisplatin-induced nephrotoxicity in male rats.
AB  - Cisplatin (CP) is a widely used anticancer drug; however, it has several side
      effects such as nephrotoxicity. Ginger, the rhizome of Zingiber officinale,
      consumed since ancient times has numerous health benefits. The objective of this
      work was to evaluate the protective effect of ginger extract (GE) against CP
      induced nephrotoxicity. CP group displayed a marked renal failure characterized
      by a significant increase in serum creatinine and blood urea nitrogen (BUN)
      levels in addition to severe histopathological and ultrastructural renal
      alterations. Also, CP group showed an increase in the immunohistochemical
      expression of Bax proapoptotic protein. In contrast, GE+CP group showed
      significant decrease in the elevated serum creatinine and BUN levels and an
      improvement in the histopathological and ultrastructural renal injury induced by
      CP. The overexpression of Bax proapoptotic protein was significantly decreased in
      the GE+CP group. Hence, the present results indicated that GE has a protective
      effect against CP-induced renal damage in rats. Thereby, such findings
      recommended the usage of GE to prevent and/or decrease the renal damage induced
      by CP chemotherapeutic treatment. 

PMID- 23552261
TI  - Sensitive determination of lead, cadmium and nickel in soil, water, vegetable and
      fruit samples using STAT-FAAS after preconcentration with activated carbon.
AB  - In this study, lead (Pb), cadmium (Cd) and nickel (Ni) were determined in soil,
      water, vegetable and fruit samples taken from around oil refinery region in
      Batman, Turkey. Digestion procedures for samples were optimized and all optimum
      parameters were used both in digestion and in determination steps. In order to
      determine Pb and Cd, slotted tube atom trap (STAT) was used to increase the
      sensitivity in atomic absorption spectrophotometry. Preconcentration procedure
      under the optimum conditions was applied to water, vegetable and fruit samples to
      determine Pb, Cd and Ni in trace levels. In soil samples, concentrations of
      analytes were found in the range of 4.0 +/- 0.2-12,000 +/- 60 mg/kg for Pb, 0.15
      +/- 0.01-3.0 +/- 0.1 mg/kg for Cd and 21 +/- 1-65 +/- 3.4 mg/kg for Ni. In all
      water samples, concentration of Ni was expressed as nanogram per milliliter
      (ng/mL) and found to be higher than Pb and Cd levels. It was observed that Pb, Cd
      and Ni concentrations varied from both plant to plant and in same plants at
      different experimental sites. Pb concentrations in vegetable and fruit samples
      interested varied between 20 +/- 2 and 160 +/- 12 ng/g, and the highest level of
      Pb was found to be in green pepper taken from 1000 m away from refinery. 

PMID- 23552262
TI  - Status of neurocognitive and oxidative stress conditions in iron-steel workers.
AB  - The aim of this study was to determine oxidative stress status as well as ferrous
      (Fe) and Copper (Cu) levels in blood, neurocognitive impairment, and clinical
      markers in iron-steel workers. A comparative cross-sectional analysis was
      performed in 50 iron-steel workers who have been in contact with Fe and Cu in
      comparison with a control group containing 50 healthy subjects in the same age
      group and sex. Blood levels of lipid peroxidation, total antioxidant capacity,
      Fe, and Cu along with neurocognitive impairment were measured in workers and
      controls. Clinical examination was accomplished to record any abnormal sign or
      symptoms. Comparing with controls, the workers showed higher blood levels of
      lipid peroxidation and Cu and also a lower total antioxidant capacity. There was
      a positive correlation between work history and interstitial lung disease that
      strengths the presumption to progress to chronic obstructive lung disease in
      future. The results indicate that exposure to a combination of Fe and Cu in iron
      steel workers induces oxidative stress. Especially, in the present case, toxic
      effect of Cu has been more than positive effects of Fe, but the combined exposure
      resulted in no such critical toxicity. 

PMID- 23552263
TI  - Lipoxygenase and urease inhibition of the aerial parts of the Polygonatum
      verticillatum.
AB  - Over expression of lipoxygenase (LOX) and urease has already contributed to the
      pathology of different human disease. Targeting the inhibition of these enzymes
      has proved great clinical utility. The aim of the present study was to
      scrutinised the inhibitory profile of the aerial parts of the Polygonatum
      verticillatum enzyme against LOX, urease, acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) using standard experimental protocols. When checked
      against lipoxygenase, the extracts revealed significant attenuation. Of the
      tested extracts, the ethyl acetate fraction was the most potent (half-maximal
      inhibitory concentration (IC(50)): 97 ug/mL) followed by aqueous fraction IC(50):
      109 ug/mL). Regarding urease inhibition, n-butanol was the most potent fraction
      (IC(50): 97 ug/mL). However, the extracts did not show significant inhibition on
      AChE and BChE. In the preliminary phytochemical tests, the aerial parts of the
      plant showed the presence of saponins, alkaloids, flavonoids, phenols, tannins
      and terpenoids. The current findings could be attributed to these groups of
      compounds.

PMID- 23552264
TI  - Evaluation of in vitro and in vivo genotoxicity of single-walled carbon
      nanotubes.
AB  - Single-walled carbon nanotubes (SWCNTs) have extensive potential industrial
      applications due to their unique physical and chemical properties; yet this also
      increases the chance of human and environment exposure to SWCNTs. Due to the
      current lack of hazardous effect information on SWNCTs, a standardized
      genotoxicity battery test was conducted to clarify the genetic toxicity potential
      of SWCNTs (diameter: 1-1.2 nm, length: ~20 MUm) according to Organization for
      Economic Cooperation and Development test guidelines 471 (bacterial reverse
      mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo
      micronuclei test) with a good laboratory practice system. The test results showed
      that the SWCNTs did not induce significant bacterial reverse mutations at 31.3
      500 MUg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537
      or in Escherichia coli strain WP2uvrA, with and without a metabolic activation
      system. Furthermore, the in vitro chromosome aberration test showed no
      significant increase in structural or numerical chromosome aberration frequencies
      at SWCNT dose levels of 12.5-50 MUg/ml in the presence and absence of metabolic
      activation. However, dose-dependent cell growth inhibition was found at all the
      SWCNT dose levels and statistically significant cytotoxic effects observed at
      certain concentrations in the presence and absence of metabolic activation.
      Finally, the SWCNTs did not evoke significant in vivo micronuclei frequencies in
      the polychromatic erythrocytes of an imprinting control region mice at 25-100
      mg/kg. Thus, according to the results of the present study, the SWCNTs were not
      found to have a genotoxic effect on the in vitro and in vivo test systems.

PMID- 23552265
TI  - UVA photoirradiation of benzo[a]pyrene metabolites: induction of cytotoxicity,
      reactive oxygen species, and lipid peroxidation.
AB  - Benzo[a]pyrene (BaP) is a prototype for studying carcinogenesis of polycyclic
      aromatic hydrocarbons (PAHs). We have long been interested in studying the
      phototoxicity of PAHs. In this study, we determined that metabolism of BaP by
      human skin HaCaT keratinocytes resulted in six identified phase I metabolites,
      for example, BaP trans-7,8-dihydrodiol (BaP t-7,8-diol), BaP t-4,5-diol, BaP t
      9,10-diol, 3-hydroxybenzo[a]pyrene (3-OH-BaP), BaP (7,10/8,9)tetrol, and BaP
      (7/8,9,10)tetrol. The photocytotoxicity of BaP, 3-OH-BaP, BaP t-7,8-diol, BaP
      trans-7,8-diol-anti-9,10-epoxide (BPDE), and BaP (7,10/8,9)tetrol in the HaCaT
      keratinocytes was examined. When irradiated with 1.0 J/cm(2) UVA light, these
      compounds when tested at doses of 0.1, 0.2, and 0.5 MUM, all induced
      photocytotoxicity in a dose-dependent manner. When photoirradiation was conducted
      in the presence of a lipid (methyl linoleate), BaP metabolites, BPDE, and three
      related PAHs, pyrene, 7,8,9,10-tetrahydro-BaP trans-7,8-diol, and 7,8,9,10
      tetrahydro-BaP trans-9,10-diol, all induced lipid peroxidation. The formation of
      lipid peroxides by BaP t-7,8-diol was inhibited by NaN3 and enhanced by
      deuterated methanol, which suggests that singlet oxygen may be involved in the
      generation of lipid peroxides. The formation of lipid hydroperoxides was
      partially inhibited by superoxide dismutase (SOD). Electron spin resonance spin
      trapping experiments indicated that both singlet oxygen and superoxide radical
      anion were generated from UVA photoirradiation of BPDE in a light dose responding
      manner. 

PMID- 23552266
TI  - Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced
      oxidative, histological and electromyographical side effects in rats.
AB  - In the present study, the beneficial effect of hesperidin (HP), a citrus
      flavonoid, on cisplatin (CP)-induced neurotoxicity was investigated. A total of
      28 rats were equally divided into four groups; the first group was kept as
      control. In the second and third groups, CP and HP were given at the doses of 7
      and 50 mg/kg/day, respectively. In the fourth group, CP and HP were given
      together at the same doses. The results indicated that although CP caused
      significant induction of lipid peroxidations and reduction in the antioxidant
      defense system potency in the brain and sciatic nerve, HP prevented these effects
      of CP. Besides, CP led to histopathological damage, mainly apoptosis, as well as
      electromyographical (EMG) changes in sciatic nerve. On the other hand, HP
      treatment reversed histopathological and EMG effects of CP. In conclusion, CP had
      severe dose-limiting neurotoxic effects and these effects of CP can be prevented
      by HP treatment. Thus, it appears that coadministration of HP with CP may be a
      useful approach to attenuate the negative effects of CP on the nervous system. 

PMID- 23552267
TI  - Trace and major element levels in rats after oral administration of diesel and
      biodiesel derived from opium poppy (Papaver somniferum L.) seeds.
AB  - The study investigated the toxic effects of diesel and biodiesel derived from
      opium poppy (Papaver somniferum L.) oil seeds on the trace and major elements in
      kidney, lung, liver, and serum of rats. By the end of 21 days, trace and major
      element concentrations in kidney, lung, and liver tissues and the serum were
      measured using inductively coupled plasma-optical emission spectroscopy. We
      observed that trace and major element levels in kidney, lung, and liver tissues
      and the serum changed. Especially, important differences were detected in trace
      and major element concentrations in kidney and lung tissues. In kidney tissue,
      the concentration differences of calcium, sodium, and zinc (Zn) were found
      between diesel and biodiesel groups. In lung tissue, the concentration
      differences of cadmium, lithium, magnesium, manganese, and Zn were found between
      diesel and biodiesel groups. Among the significant findings, Zn concentration in
      serum and liver tissue of diesel and biodiesel were different from control (p <
      0.05). However, the metal levels of biodiesel group were similar to control
      group. Due to lesser toxicity of biodiesel, it could be considered as an
      alternate fuel. 

PMID- 23552268
TI  - Potential anticancer activity of carvone in N2a neuroblastoma cell line.
AB  - Carvone (CVN) is a monocyclic monoterpene found in the essential oils of Mentha
      spicata var. crispa (Lamiaceae) and Carum carvi L. (Apiaceae) plants and has been
      reported to have antioxidant, antimicrobial, anticonvulsant, and antitumor
      activities. The beneficial health properties of CVN have encouraged us to look
      into its anticancer activity. To the best of our knowledge, reports are not
      available on the anticancer activity of CVN in cultured primary rat neuron and
      N2a neuroblastoma (NB) cells. Therefore, the present study is an attempt toward
      exploring the potential anticancer activity of CVN, if any, in cultured primary
      rat neuron and N2a NB cells. Our results indicated that CVN (only at 25 mg/L)
      treatment led to an increase in the total antioxidant capacity levels in cultured
      primary rat neuron cells compared with control cells. Also, CVN (at
      concentrations higher than 100 mg/L) treatment led to an increase in the total
      oxidative stress levels in both cell types. The mean values of the total scores
      of cells showing DNA damage (for comet assay) were not found to be significantly
      different from the control values in both cells (p > 0.05). On the other hand,
      after 24 h treatment with CVN, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay showed that CVN application significantly
      reduced the cell viability rates in both cell types at concentrations higher than
      100 mg/L. Summarizing, our data suggest that CVN represents little potential for
      promising anticancer agent to improve brain tumors therapy.

PMID- 23552269
TI  - Effect of sugammadex on rocuronium induced changes in pancreatic mast cells.
AB  - Mast cells play a vital role in hypersensitivity reactions. Rocuronium is known
      to cause mast cell mobilization, hypersensitivity, and pancreatitis. The aim of
      this study was to investigate the effects of sugammadex on pancreatic changes due
      to rocuronium. A total of 42 Sprague-Dawley male rats were divided into six equal
      groups to receive either rocuronium 1 mg/kg intravenously (i.v., R group),
      rocuronium 1 mg/kg + sugammadex 16 mg/kg i.v. (RS16 group), rocuronium 1 mg/kg +
      sugammadex 96 mg/kg i.v. (RS96 group), sugammadex 16 mg/kg (S16), sugammadex 96
      mg/kg i.v. (S96 group), or 0.9% sodium chloride (control group). Sugammadex was
      administered 5s later following rocuronium. In R group, mast count was higher,
      and the distribution rate of granules and nuclear changes were different compared
      with other groups. Distribution rate of granules in groups S16 and S96 were
      similar to the control group and lower compared with other groups. The amount of
      mast cells and granule density in groups RS16 and RS96 was lower compared with R
      group. The amount of mast cells in groups RS16 and RS96 was significantly lower
      compared with other treatment groups. These results suggest that sugammadex may
      have an inhibitory effect on mobilization and morphological changes in pancreatic
      mast cells induced by administration of rocuronium and sugammadex in rats.

PMID- 23552270
TI  - Developing a multidisciplinary robotic surgery quality assessment program.
AB  - The objective of this study was to test the feasibility of a novel quality
      improvement (QI) program designed to incorporate multiple robotic surgical sub
      specialties in one health care system. A robotic surgery quality assessment
      program was developed by The Ohio State University College of Medicine (OSUMC) in
      conjunction with The Ohio State University Medical Center Quality Improvement and
      Operations Department. A retrospective review of cases was performed using data
      interrogated from the OSUMC Information Warehouse from January 2007 through
      August 2009. Robotic surgery cases (n=2200) were assessed for operative times,
      length of stay (LOS), conversions, returns to surgery, readmissions and
      cancellations as potential quality indicators. An actionable and reproducible
      framework for the quality measurement and assessment of a multidisciplinary and
      interdepartmental robotic surgery program was successfully completed
      demonstrating areas for improvement opportunities. This report supports that
      standard quality indicators can be applied to multiple specialties within a
      health care system to develop a useful quality tracking and assessment tool in
      the highly specialized area of robotic surgery.

PMID- 23552271
TI  - What should it take to describe a substance or product as 'sperm-safe'.
AB  - BACKGROUND: Male reproductive potential continues to be adversely affected by
      many environmental, industrial and pharmaceutical toxins. Pre-emptive testing for
      reproductive toxicological (side-)effects remains limited, or even non-existent.
      Many products that come into direct contact with spermatozoa lack adequate
      testing for the absence of adverse effects, and numerous products that are
      intended for exposure to spermatozoa have only a general assumption of safety
      based on the absence of evidence of actual harm. Such assumptions can have
      unfortunate adverse impacts on at-risk individuals (e.g. couples who are trying
      to conceive), illustrating a clear need for appropriate up-front testing to
      establish actual 'sperm safety'. METHODS: After compiling a list of general areas
      within the review's scope, relevant literature and other information was obtained
      from the authors' personal professional libraries and archives, and supplemented
      as necessary using PubMed and Google searches. Review by co-authors identified
      and eliminated errors of omission or bias. RESULTS: This review provides an
      overview of the broad range of substances, materials and products that can affect
      male fertility, especially through sperm fertilizing ability, along with a
      discussion of practical methods and bioassays for their evaluation. It is
      concluded that products can only be claimed to be 'sperm-safe' after performing
      objective, properly designed experimental studies; extrapolation from supposed
      predicate products or other assumptions cannot be trusted. CONCLUSIONS: We call
      for adopting the precautionary principle, especially when exposure to a product
      might affect not only a couple's fertility potential but also the health of
      resulting offspring and perhaps future generations.

PMID- 23552272
TI  - Emission spectra profiling of fluorescent proteins in living plant cells.
AB  - BACKGROUND: Fluorescence imaging at high spectral resolution allows the
      simultaneous recording of multiple fluorophores without switching optical
      filters, which is especially useful for time-lapse analysis of living cells. The
      collected emission spectra can be used to distinguish fluorophores by a
      computation analysis called linear unmixing. The availability of accurate
      reference spectra for different fluorophores is crucial for this type of
      analysis. The reference spectra used by plant cell biologists are in most cases
      derived from the analysis of fluorescent proteins in solution or produced in
      animal cells, although these spectra are influenced by both the cellular
      environment and the components of the optical system. For instance, plant cells
      contain various autofluorescent compounds, such as cell wall polymers and
      chlorophyll, that affect the spectral detection of some fluorophores. Therefore,
      it is important to acquire both reference and experimental spectra under the same
      biological conditions and through the same imaging systems. RESULTS: Entry clones
      (pENTR) of fluorescent proteins (FPs) were constructed in order to create C- or N
      terminal protein fusions with the MultiSite Gateway recombination technology. The
      emission spectra for eight FPs, fused C-terminally to the A- or B-type cyclin
      dependent kinases (CDKA;1 and CDKB1;1) and transiently expressed in epidermal
      cells of tobacco (Nicotiana benthamiana), were determined by using the Olympus
      FluoViewTM FV1000 Confocal Laser Scanning Microscope. These experimental spectra
      were then used in unmixing experiments in order to separate the emission of
      fluorophores with overlapping spectral properties in living plant cells.
      CONCLUSIONS: Spectral imaging and linear unmixing have a great potential for
      efficient multicolor detection in living plant cells. The emission spectra for
      eight of the most commonly used FPs were obtained in epidermal cells of tobacco
      leaves and used in unmixing experiments. The generated set of FP Gateway entry
      vectors represents a valuable resource for plant cell biologists.

PMID- 23552275
TI  - Local anesthetic toxicity during awake craniotomy.

PMID- 23552273
TI  - The relationship between DXA-based and anthropometric measures of visceral fat
      and morbidity in women.
AB  - BACKGROUND: Excess accumulation of visceral fat is a prominent risk factor for
      cardiovascular and metabolic morbidity. While computed tomography (CT) is the
      gold standard to measure visceral adiposity, this is often not possible for large
      studies - thus valid, but less expensive and intrusive proxy measures of visceral
      fat are required such as dual-energy X-ray absorptiometry (DXA). Study aims were
      to a) identify a valid DXA-based measure of visceral adipose tissue (VAT), b)
      estimate VAT heritability and c) assess visceral fat association with morbidity
      in relation to body fat distribution. METHODS: A validation sample of 54 females
      measured for detailed body fat composition - assessed using CT, DXA and
      anthropometry - was used to evaluate previously published predictive models of CT
      measured visceral fat. Based upon a validated model, we realised an out-of-sample
      estimate of abdominal VAT area for a study sample of 3457 female volunteer twins
      and estimated VAT area heritability using a classical twin study design.
      Regression and residuals analyses were used to assess the relationship between
      adiposity and morbidity. RESULTS: Published models applied to the validation
      sample explained >80% of the variance in CT-measured visceral fat. While CT
      visceral fat was best estimated using a linear regression for waist
      circumference, CT body cavity area and total abdominal fat (R2 = 0.91),
      anthropometric measures alone predicted VAT almost equally well (CT body cavity
      area and waist circumference, R2 = 0.86). Narrow sense VAT area heritability for
      the study sample was estimated to be 58% (95% CI: 51-66%) with a shared familial
      component of 24% (17-30%). VAT area is strongly associated with type 2 diabetes
      (T2D), hypertension (HT), subclinical atherosclerosis and liver function tests.
      In particular, VAT area is associated with T2D, HT and liver function (alanine
      transaminase) independent of DXA total abdominal fat and body mass index (BMI).
      CONCLUSIONS: DXA and anthropometric measures can be utilised to derive estimates
      of visceral fat as a reliable alternative to CT. Visceral fat is heritable and
      appears to mediate the association between body adiposity and morbidity. This
      observation is consistent with hypotheses that suggest excess visceral adiposity
      is causally related to cardiovascular and metabolic disease.

PMID- 23552276
TI  - Image-guided intracranial endosonography.
AB  - BACKGROUND: Although the skull limits applicability of sonography, bedside
      intracranial endosonography might be an alternative to computed tomography scans
      to detect adverse events in sedated patients. However, the usefulness of
      intracranial endosonography for potential clinical application has not been
      evaluated. The present study was designed to investigate the suitability of an
      image-guided intracranial endosonography (IGIE) catheter for intracranial
      ultrasound imaging in an ex vivo phantom model and in a large animal model.
      MATERIALS AND METHODS: IGIE was evaluated in a cranial phantom and a porcine
      intracranial hemorrhage (ICH) model. Two anesthetized animals underwent an
      initial magnetic resonance imaging (MRI) scan, followed by placement of an
      endosonography catheter in the frontal lobe. After anatomic imaging, an
      experimental ICH was placed in the contralateral hemisphere. B-scan imaging,
      duplex, Doppler sonography, and a second MRI were performed. A standard image
      guiding device tracked the ultrasound catheter. RESULTS: Endosonography provided
      high-definition imaging of intracranial structures. Image guidance allowed
      direction of the catheter to and intuitive identification of anatomic structures.
      Doppler imaging allowed analysis of blood flow in intracranial vessels.
      Ultrasound imaging was used to monitor evolution of ICH and the resulting brain
      edema in real time. Coregistration of ultrasound and MRI images acquired after
      ICH placement demonstrated the high accuracy of the spatial resolution of IGIE
      (largest mismatch <5 mm). CONCLUSIONS: IGIE provides high-definition images of
      intracranial structures, Doppler analysis of blood flow, and real-time monitoring
      of intracranial structural lesions. We suggest that IGIE might prove a valuable
      tool for intracranial monitoring of sedated patients over extended time periods.

PMID- 23552278
TI  - An acute neurological syndrome with cerebrovascular and parkinsonian clinical
      features associated with perioperative SNRI withdrawal.

PMID- 23552274
TI  - "One of those areas that people avoid" a qualitative study of implementation in
      miscarriage management.
AB  - BACKGROUND: Miscarriage is common and often managed by specialists in the
      operating room despite evidence that office-based manual vacuum aspiration (MVA)
      is safe, effective, and saves time and money. Family Medicine residents are not
      routinely trained to manage miscarriages using MVA, but have the potential to
      increase access to this procedure. This process evaluation sought to identify
      barriers and facilitators to implementation of office-based MVA for miscarriage
      in Family Medicine residency sites in Washington State. METHODS: The Residency
      Training Initiative in Miscarriage Management (RTI-MM) is a theory-based,
      multidimensional practice change initiative. We used qualitative methods to
      identify barriers and facilitators to successful implementation of the RTI-MM.
      RESULTS: Thirty-six RTI-MM participants completed an interview. We found that the
      common major barriers to implementation were low volume and a perception of
      miscarriage as emotional and/or like abortion, while the inclusion of support
      staff in training and effective champions facilitated successful implementation
      of MVA services. CONCLUSION: Perceived characteristics of the innovation that may
      conflict with cultural fit must be explicitly addressed in dissemination
      strategies and support staff should be included in practice change initiatives.
      Questions remain about how to best support champions and influence perceptions of
      the innovation. Our study findings contribute programmatically (to improve the
      RTI-MM), and to broader theoretical knowledge about practice change and
      implementation in health service delivery.

PMID- 23552279
TI  - Unanticipated blood loss and management of a patient with bombay phenotype coming
      for bone flap replacement: a lesson learnt.

PMID- 23552280
TI  - Shall we dance? - The effect of information presentations on negotiation
      processes and outcomes.
AB  - The way information is presented influences human decision making and is
      consequently highly relevant to electronically supported negotiations. The
      present study analyzes in a controlled laboratory experiment how information
      presentation in three alternative formats (table, history graph and dance graph)
      influences the negotiators' behavior and negotiation outcomes. The results show
      that graphical information presentation supports integrative behavior and the use
      of non-compensatory strategies. Furthermore, information about the opponents'
      preferences increases the quality of outcomes but decreases post-negotiation
      satisfaction of negotiators. The implications for system designers are discussed.

PMID- 23552281
TI  - Effect of local use of L-carnitine after myringotomy on myringosclerosis
      development in rats.
AB  - OBJECTIVES: This study aimed to investigate the effect of local and
      intraperitoneal administration of L-carnitine on the prevention of experimentally
      induced myringosclerosis, and to compare treatment efficiency. METHODS: Twenty
      four Albino-Wistar rats (48 ears) were bilaterally myringotomised and divided
      randomly into four groups: group one received no treatment, group two received
      intraperitoneal L-carnitine, group three received local L-carnitine, and group
      four received both intraperitoneal and local L-carnitine. On the 15th day after
      treatment, tympanic membranes were harvested and evaluated histopathologically
      for myringosclerotic plaque formation, fibroblastic proliferation, tympanic
      membrane thickness and new vessel formation. RESULTS: The group one tympanic
      membranes showed extensive thickness, and the incidence of myringosclerosis and
      fibroblast proliferation were greater than in groups two and four. There were
      statistically significant differences in tympanic membrane thickness between
      groups three and four, and in myringosclerosis incidence and fibroblast
      proliferation, comparing groups two, three and four. CONCLUSION: Myringosclerosis
      development was significantly reduced in rats receiving myringotomy plus
      intraperitoneal L-carnitine. Intraperitoneal L-carnitine administration prevented
      fibroblastic proliferation and tympanic membrane thickening (both of which cause
      further tympanic membrane destruction), thus reducing myringotomy-associated
      morbidity. Local L-carnitine administration had limited effectiveness in this
      experimental setting.

PMID- 23552282
TI  - CNGA3 achromatopsia-associated mutation potentiates the phosphoinositide
      sensitivity of cone photoreceptor CNG channels by altering intersubunit
      interactions.
AB  - Cyclic nucleotide-gated (CNG) channels are critical for sensory transduction in
      retinal photoreceptors and olfactory receptor cells; their activity is modulated
      by phosphoinositides (PIPn) such as phosphatidylinositol 4,5-bisphosphate (PIP2)
      and phosphatidylinositol 3,4,5-trisphosphate (PIP3). An achromatopsia-associated
      mutation in cone photoreceptor CNGA3, L633P, is located in a carboxyl (COOH)
      terminal leucine zipper domain shown previously to be important for channel
      assembly and PIPn regulation. We determined the functional consequences of this
      mutation using electrophysiological recordings of patches excised from cells
      expressing wild-type and mutant CNG channel subunits. CNGA3-L633P subunits formed
      functional channels with or without CNGB3, producing an increase in apparent cGMP
      affinity. Surprisingly, L633P dramatically potentiated PIPn inhibition of
      apparent cGMP affinity for these channels. The impact of L633P on PIPn
      sensitivity depended on an intact amino (NH2) terminal PIPn regulation module.
      These observations led us to hypothesize that L633P enhances PIPn inhibition by
      altering the coupling between NH2- and COOH-terminal regions of CNGA3. A
      recombinant COOH-terminal fragment partially restored normal PIPn sensitivity to
      channels with COOH-terminal truncation, but L633P prevented this effect.
      Furthermore, coimmunoprecipitation of channel fragments, and thermodynamic
      linkage analysis, also provided evidence for NH2-COOH interactions. Finally,
      tandem dimers of CNGA3 subunits that specify the arrangement of subunits
      containing L633P and other mutations indicated that the putative interdomain
      interaction occurs between channel subunits (intersubunit) rather than
      exclusively within the same subunit (intrasubunit). Collectively, these studies
      support a model in which intersubunit interactions control the sensitivity of
      cone CNG channels to regulation by phosphoinositides. Aberrant channel regulation
      may contribute to disease progression in patients with the L633P mutation. 

PMID- 23552283
TI  - Role of the fourth transmembrane domain in proton-coupled folate transporter
      function as assessed by the substituted cysteine accessibility method.
AB  - The proton-coupled folate transporter (PCFT, SLC46A1) mediates folate transport
      across the apical brush-border membrane of the proximal small intestine and the
      basolateral membrane of choroid plexus ependymal cells. Two loss-of-function
      mutations in PCFT, which are the basis for hereditary folate malabsorption, have
      been identified within the fourth transmembrane domain (TMD4) in subjects with
      this disorder. We have employed the substituted Cys accessibility method (SCAM)
      to study the accessibilities of all residues in TMD4 and their roles in folate
      substrate binding to the carrier. When residues 146-167 were replaced by Cys, all
      except R148C were expressed at the cell surface. Modification of five of these
      substituted Cys residues (positions 147, 152, 157, 158, and 161) by
      methanethiosulfonate (MTS) reagents led to reduction of PCFT function. All five
      residues could be labeled with N-biotinylaminoethyl-MTS, and this could be
      blocked by the high-affinity PCFT substrate pemetrexed. Pemetrexed also protected
      PCFT mutant function from inhibitory modification of the substituted Cys at
      positions 157, 158, and 161 by a MTS. The findings indicate that these five
      residues in TMD4 are accessible to the aqueous translocation pathway, play a role
      in folate substrate binding, and are likely located within or near the folate
      binding pocket. A homology model of PCFT places three of these residues, Phe157,
      Gly158, and Leu161, within a breakpoint in the midportion of TMD4, a region that
      likely participates in alterations in the PCFT conformational state during
      carrier cycling.

PMID- 23552285
TI  - Distinct patterns of histone modifications at cardiac-specific gene promoters
      between cardiac stem cells and mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) possess different
      potential to develop into cardiomyocytes. The mechanism underlying cardiomyogenic
      capacity of MSCs and CSCs remains elusive. It is well established that histone
      modifications correlate with gene expression and contribute to cell fate
      commitment. Here we hypothesize that specific histone modifications accompany
      cardiac-specific gene expression, thus determining the differentiation capacity
      of MSCs and CSCs toward heart cells. Our results indicate that, at the promoter
      regions of cardiac-specific genes (Myh6, Myl2, Actc1, Tnni3, and Tnnt2), the
      levels of histone acetylation of H3 (acH3) and H4 (acH4), as a mark indicative of
      gene activation, were higher in CSCs (Sca-1(+)CD29(+)) than MSCs. Additionally,
      lower binding levels of histone deacetylase (HDAC) 1 and HDAC2 at promoter
      regions of cardiac-specific genes were noticed in CSCs than MSCs. Treatment with
      trichostatin A, an HDAC inhibitor, upregulated cardiac-specific gene expression
      in MSCs. Suppression of HDAC1 or HDAC2 expression by small interfering RNAs led
      to increased cardiac gene expression and was accompanied by enhanced acH3 and
      acH4 levels at gene loci. We conclude that greater levels of histone acetylation
      at cardiac-specific gene loci in CSCs than MSCs reflect a stronger potential for
      CSCs to develop into cardiomyocytes. These lineage-differential histone
      modifications are likely due to less HDAC recruitment at cardiac-specific gene
      promoters in CSCs than MSCs.

PMID- 23552286
TI  - Prolyl carboxypeptidase: a forgotten kidney angiotensinase. Focus on
      "Identification of prolyl carboxypeptidase as an alternative enzyme for
      processing of renal angiotensin II using mass spectrometry".

PMID- 23552284
TI  - The role of the vascular dendritic cell network in atherosclerosis.
AB  - A complex role has been described for dendritic cells (DCs) in the potentiation
      and control of vascular inflammation and atherosclerosis. Resident vascular DCs
      are found in the intima of atherosclerosis-prone vascular regions exposed to
      disturbed blood flow patterns. Several phenotypically and functionally distinct
      vascular DC subsets have been described. The functional heterogeneity of these
      cells and their contributions to vascular homeostasis, inflammation, and
      atherosclerosis are only recently beginning to emerge. Here, we review the
      available literature, characterizing the origin and function of known vascular DC
      subsets and their important role contributing to the balance of immune activation
      and immune tolerance governing vascular homeostasis under healthy conditions. We
      then discuss how homeostatic DC functions are disrupted during atherogenesis,
      leading to atherosclerosis. The effectiveness of DC-based "atherosclerosis
      vaccine" therapies in the treatment of atherosclerosis is also reviewed. We
      further provide suggestions for distinguishing DCs from macrophages and discuss
      important future directions for the field. 

PMID- 23552287
TI  - Role of self-sufficiency, productivity and diversification on the economic
      sustainability of farming systems with autochthonous sheep breeds in less
      favoured areas in Southern Europe.
AB  - Traditional mixed livestock cereal- and pasture-based sheep farming systems in
      Europe are threatened by intensification and specialisation processes. However,
      the intensification process does not always yield improved economic results or
      efficiency. This study involved a group of farmers that raised an autochthonous
      sheep breed (Ojinegra de Teruel) in an unfavourable area of North-East Spain.
      This study aimed to typify the farms and elucidate the existing links between
      economic performance and certain sustainability indicators (i.e. productivity,
      self-sufficiency and diversification). Information was obtained through direct
      interviews with 30 farms (73% of the farmers belonging to the breeders
      association). Interviews were conducted in 2009 and involved 32 indicators
      regarding farm structure, management and economic performance. With a principal
      component analysis, three factors were obtained explaining 77.9% of the original
      variance. This factors were named as inputs/self-sufficiency, which included the
      use of on-farm feeds, the amount of variable costs per ewe and economic
      performance; productivity, which included lamb productivity and economic
      autonomy; and productive orientation, which included the degree of specialisation
      in production. A cluster analysis identified the following four groups of farms:
      high-input intensive system; low-input self-sufficient system; specialised
      livestock system; and diversified crops-livestock system. In conclusion, despite
      the large variability between and within groups, the following factors that
      explain the economic profitability of farms were identified: (i) high feed self
      sufficiency and low variable costs enhance the economic performance (per labour
      unit) of the farms; (ii) animal productivity reduces subsidy dependence, but does
      not necessarily imply better economic performance; and (iii) diversity of
      production enhances farm flexibility, but is not related to economic performance.

PMID- 23552288
TI  - Evaluation of an advanced physical diagnosis course using consumer preferences
      methods: the nominal group technique.
AB  - BACKGROUND: Current evaluation tools of medical school courses are limited by the
      scope of questions asked and may not fully engage the student to think on areas
      to improve. The authors sought to explore whether a technique to study consumer
      preferences would elicit specific and prioritized information for course
      evaluation from medical students. METHODS: Using the nominal group technique (4
      sessions), 12 senior medical students prioritized and weighed expectations and
      topics learned in a 100-hour advanced physical diagnosis course (4-week course;
      February 2012). Students weighted their top 3 responses (top = 3, middle = 2 and
      bottom = 1). RESULTS: Before the course, 12 students identified 23 topics they
      expected to learn; the top 3 were review sensitivity/specificity and high-yield
      techniques (percentage of total weight, 18.5%), improving diagnosis (13.8%) and
      reinforce usual and less well-known techniques (13.8%). After the course,
      students generated 22 topics learned; the top 3 were practice and reinforce
      advanced maneuvers (25.4%), gaining confidence (22.5%) and learn the evidence
      (16.9%). The authors observed no differences in the priority of responses before
      and after the course (P = 0.07). CONCLUSIONS: In a physical diagnosis course,
      medical students elicited specific and prioritized information using the nominal
      group technique. The course met student expectations regarding education of the
      evidence-based physical examination, building skills and confidence on the proper
      techniques and maneuvers and experiential learning. The novel use for curriculum
      evaluation may be used to evaluate other courses-especially comprehensive and
      multicomponent courses.

PMID- 23552289
TI  - Monomeric actin required for INO80 remodeling.

PMID- 23552290
TI  - Expanding the functional repertoire of macrodomains.

PMID- 23552291
TI  - NMR disentangles a dynamic disaggregase machinery.

PMID- 23552292
TI  - Allostery through DNA.

PMID- 23552297
TI  - Social networking sites and older users - a systematic review.
AB  - BACKGROUND: Social networking sites can be beneficial for senior citizens to
      promote social participation and to enhance intergenerational communication.
      Particularly for older adults with impaired mobility, social networking sites can
      help them to connect with family members and other active social networking
      users. The aim of this systematic review is to give an overview of existing
      scientific literature on social networking in older users. METHODS: Computerized
      databases were searched and 105 articles were identified and screened using
      exclusion criteria. After exclusion of 87 articles, 18 articles were included,
      reviewed, classified, and the key findings were extracted. Common findings are
      identified and critically discussed and possible future research directions are
      outlined. RESULTS: The main benefit of using social networking sites for older
      adults is to enter in an intergenerational communication with younger family
      members (children and grandchildren) that is appreciated by both sides.
      Identified barriers are privacy concerns, technical difficulties and the fact
      that current Web design does not take the needs of older users into account.
      CONCLUSIONS: Under the conditions that these problems are carefully addressed,
      social networking sites have the potential to support today's and tomorrow's
      communication between older and younger family members.

PMID- 23552298
TI  - Author reply: To PMID 22928174.

PMID- 23552296
TI  - Transcription-replication encounters, consequences and genomic instability.
AB  - To ensure accurate duplication of genetic material, the replication fork must
      overcome numerous natural obstacles on its way, including transcription complexes
      engaged along the same template. Here we review the various levels of
      interdependence between transcription and replication processes and how different
      types of encounters between RNA- and DNA-polymerase complexes may result in
      clashes of those machineries on the DNA template and thus increase genomic
      instability. In addition, we summarize strategies evolved in bacteria and
      eukaryotes to minimize the consequences of collisions, including R-loop formation
      and topological stresses.

PMID- 23552299
TI  - One-pot fabrication of single-crystalline octahedral Pt-Cu nanoframes and their
      enhanced electrocatalytic activity.
AB  - Octahedral Pt-Cu nanoframes have been synthesized by a one-pot aqueous method.
      Due to the unique structure and possible synergetic effect of Pt and Cu
      components, these octahedral Pt-Cu nanoframes exhibited significantly enhanced
      catalytic activity toward the electro-oxidation of formic acid in comparison with
      commercial Pt black and Pt/C catalysts.

PMID- 23552300
TI  - Dramatic enhancement of carrier mobility via effective secondary structural
      arrangement resulting from the substituents in a porphyrin transistor.
AB  - OFET devices based on single-crystals of two different porphyrin derivatives
      display excellent mobilities of 2.57 and 0.48 cm(2) V(-1) s(-1). Although they
      generate similar J-aggregations, the dramatic enhancement of mobility obtained
      using porphyrin 1 is due to the well-confined secondary structural arrangement
      caused by substituents on the porphyrin ring.

PMID- 23552301
TI  - Novel Co-based metal-organic frameworks and their magnetic properties using
      asymmetrically binding 4-(4'-carboxyphenyl)-1,2,4-triazole.
AB  - Two novel Co-based metal-organic frameworks (MOFs) were synthesised and
      characterised using an asymmetrically binding ligand, 4-(4'-carboxyphenyl)-1,2,4
      triazole (Hcpt). The isolated [Co3(II)(MU3-O)(OH)(cpt)3(H2O)2]n.xH2O.yDMF, Co
      MOF1, exhibits a rhombohedral crystal structure (space group, P63/mc), with a
      trinuclear cobalt core that resembles the MIL88 series. This MOF shows
      paramagnetic behaviour down to 2 K with no saturation of magnetisation up to 7 T.
      This is presumably due to a geometrically frustrated triangular arrangement of Co
      spins. The two-dimensional complex, [Co(II)(cpt)(N3)]n, Co-MOF2, crystallises in
      a monoclinic crystal system (space group, C2/m). The magnetic measurements reveal
      metamagnetic behaviour for this complex with a critical field in the range of 700
      1000 Oe.

PMID- 23552303
TI  - Late presentation of colorectal cancer in a vulnerable population.
AB  - OBJECTIVES: We examined colorectal cancer (CRC) stage at presentation and
      mortality in a vulnerable population compared with nationally representative
      data. METHODS: CRC cases were identified from San Francisco General Hospital
      (SFGH) and the Surveillance Epidemiology and End Results (SEER) database.
      RESULTS: Fifty-five percent of the SFGH cohort presented with advanced disease,
      compared with 44% of the SEER cohort. Increased risk of advanced stage at
      presentation at SFGH compared with SEER was most evident among blacks and Asians.
      There was weak evidence for worse survival at SFGH compared with SEER overall.
      This varied by race with poorer survival at SFGH among whites and possibly blacks
      but some evidence for better survival among Asians. Among CRC patients at SFGH,
      Asians and Hispanics had better survival than whites and blacks. At SFGH, 44% had
      a diagnosis of CRC within 1 year of establishing care there. Of those who had
      established care at SFGH for at least 1 year, only 22% had exposure to CRC
      screening tests. CONCLUSIONS: These findings allow examination of CRC
      presentation by ethnicity in vulnerable populations and identify areas where
      access and utilization of CRC screening can be improved.

PMID- 23552304
TI  - HCV RNA viral load assessments in the era of direct-acting antivirals.
AB  - Recent regulatory approvals of the NS3/4A protease inhibitors boceprevir and
      telaprevir launched a new therapeutic era for hepatitis C virus (HCV) genotype 1
      infection. Decisions to shorten, extend, or stop treatment with these direct
      acting antiviral (DAA) regimens require accurate quantification of serum HCV RNA
      levels. To effectively use DAA therapies, clinicians must understand performance
      characteristics of HCV RNA real-time PCR assays and the clinical significance of
      HCV RNA that is detectable below the lower limit of quantification. This review
      summarizes terms used to report HCV RNA viral load results, explains the
      analytical performance of the PCR assay used in the clinical trials of boceprevir
      and telaprevir, and compares currently available commercial assays.

PMID- 23552305
TI  - Images of the month: heterotopic gastric mucosa mimicking rectal neoplasm on
      colonoscopy.

PMID- 23552310
TI  - Response to Valente et al.

PMID- 23552311
TI  - Celiac disease and CFTR mutations in patients with chronic asymptomatic
      pancreatic hyperenzymemia.

PMID- 23552312
TI  - Observations on the paper of Carroccio et al. "non-celiac wheat sensitivity
      diagnosed by double-blind placebo-controlled challenge: exploring a new clinical
      entity".

PMID- 23552313
TI  - Response to Villanacci et al.

PMID- 23552314
TI  - Hepatitis B vaccine in IBD.

PMID- 23552315
TI  - Response to Tung et al.

PMID- 23552316
TI  - Strongyloides hyperinfection as a mimic of inflammatory bowel disease.

PMID- 23552317
TI  - Observation of wound-closure outcomes using tissue adhesive plus metal clip after
      endoscopic upper gastrointestinal muscularis propria tumor resection.

PMID- 23552318
TI  - NISIN and Clostridium difficile: a potentially effective treatment for an
      increasingly problematic disease.

PMID- 23552319
TI  - Impact of Helicobacter pylori Infection on colon oncogenesis.

PMID- 23552320
TI  - Appendectomy is not associated with adverse outcomes in clostridium difficile
      infection: a population-based study.

PMID- 23552323
TI  - Evolution of active catalysts for the selective oxidative dehydrogenation of
      methanol on Fe2O3 surface doped with Mo oxide.
AB  - Iron molybdate catalysts are used for the selective oxidation of methanol to
      formaldehyde. In this paper we have attempted to understand what determines high
      selectivity in this reaction system by doping haematite with surface layers of Mo
      by incipient wetness impregnation. This works well and the Mo appears to form
      finely dispersed layers. Even very low loadings of Mo have a marked effect on
      improving the selectivity to formaldehyde. Haematite itself is a very poor
      catalyst with high selectivity to combustion products, whereas, when only 0.25
      monolayers of Mo are deposited on the surface, formaldehyde and CO selectivities
      are greatly enhanced and CO2 production is greatly diminished. However, even with
      as much as seven monolayers of Mo dosed on to the surface, these materials
      achieve much less selectivity to formaldehyde at high conversion than do the
      industrial catalysts. The reason for this is that the Mo forms a 'skin' of ferric
      molybdate on a core of iron oxide, but does not produce a pure Mo oxide monolayer
      on the surface, a situation which is essential for very high yields of
      formaldehyde. 

PMID- 23552324
TI  - Fertility drug use and the risk of ovarian tumors in infertile women: a case
      control study.
AB  - OBJECTIVE: To assess the influence of infertility and fertility drugs on risk of
      ovarian tumors. DESIGN: Case-control study (Mayo Clinic Ovarian Cancer Study).
      SETTING: Ongoing academic study of ovarian cancer. PATIENT(S): A total of 1,900
      women (1,028 with ovarian tumors and 872 controls, frequency matched on age and
      region of residence) who had provided complete information in a self-report
      questionnaire about history of infertility and fertility drug use.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Effect of infertility history,
      use of fertility drugs and oral contraception, and gravidity on the risk of
      ovarian tumor development, after controlling for potential confounders.
      RESULT(S): Among women who had a history of infertility, use of fertility drugs
      was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile
      women who used fertility drugs were not at increased risk of developing ovarian
      tumors compared with infertile women who did not use fertility drugs; the
      adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when
      stratified by gravidity and when analyzed separately for borderline versus
      invasive tumors. CONCLUSION(S): We found no statistically significant association
      between fertility drug use and risk of ovarian tumors. Further larger,
      prospective studies are needed to confirm this observation.

PMID- 23552325
TI  - Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in
      older adults: a population-based cohort study.
AB  - BACKGROUND: Some evidence suggests that chlorthalidone may be superior to
      hydrochlorothiazide for the treatment of hypertension. OBJECTIVE: To compare the
      effectiveness and safety of chlorthalidone and hydrochlorothiazide in older
      adults. DESIGN: Propensity score-matched observational cohort study with up to 5
      years of follow-up. SETTING: Ontario, Canada. PATIENTS: All individuals aged 66
      years or older who were newly treated with chlorthalidone or hydrochlorothiazide
      and were not hospitalized for heart failure, stroke, or myocardial infarction in
      the prior year were eligible for inclusion. Each chlorthalidone recipient was
      matched to up to 2 hydrochlorothiazide recipients on the basis of age, sex, year
      of treatment initiation, and propensity score. MEASUREMENTS: The primary outcome
      was a composite of death or hospitalization for heart failure, stroke, or
      myocardial infarction. Safety outcomes included hospitalization with hypokalemia
      or hyponatremia. RESULTS: A total of 29 873 patients were studied. During follow
      up, chlorthalidone recipients (n = 10 384) experienced the primary outcome at a
      rate of 3.2 events per 100 person-years of follow-up, and hydrochlorothiazide
      recipients experienced 3.4 events per 100 person-years of follow-up (adjusted
      hazard ratio, 0.93 [95% CI, 0.81 to 1.06]). Patients treated with chlorthalidone
      were more likely to be hospitalized with hypokalemia (adjusted hazard ratio, 3.06
      [CI, 2.04 to 4.58]) or hyponatremia (adjusted hazard ratio, 1.68 [CI, 1.24 to
      2.28]). In 9 post hoc analyses comparing patients initially prescribed 12.5, 25,
      or 50 mg of chlorthalidone per day with those prescribed 12.5, 25, or 50 mg of
      hydrochlorothiazide per day, the former were more likely to be hospitalized with
      hypokalemia for all 6 comparisons in which a statistically significant
      association was found. The results of other effectiveness and safety outcomes
      were also consistent with those of the main analysis. LIMITATION: Unmeasured
      differences in baseline characteristics or physician treatment approaches or an
      insufficiently large sample may have limited the ability to detect small
      differences in the comparative effectiveness of the drugs. CONCLUSION: As
      typically prescribed, chlorthalidone in older adults was not associated with
      fewer adverse cardiovascular events or deaths than hydrochlorothiazide. However,
      it was associated with a greater incidence of electrolyte abnormalities,
      particularly hypokalemia. PRIMARY FUNDING SOURCE: Ontario Ministry of Health and
      Long-Term Care.

PMID- 23552326
TI  - Novel monosaccharide fermentation products in Caldicellulosiruptor
      saccharolyticus identified using NMR spectroscopy.
AB  - BACKGROUND: Caldicellulosiruptor saccharolyticus is a thermophilic, Gram
      positive, non-spore forming, strictly anaerobic bacterium of interest in
      potential industrial applications, including the production of biofuels such as
      hydrogen or ethanol from lignocellulosic biomass through fermentation. High
      resolution, solution-state nuclear magnetic resonance (NMR) spectroscopy is a
      useful method for the identification and quantification of metabolites that
      result from growth on different substrates. NMR allows facile resolution of
      isomeric (identical mass) constituents and does not destroy the sample. RESULTS:
      Profiles of metabolites produced by the thermophilic cellulose-degrading
      bacterium Caldicellulosiruptor saccharolyticus DSM 8903 strain following growth
      on different monosaccharides (D-glucose, D-mannose, L-arabinose, D-arabinose, D
      xylose, L-fucose, and D-fucose) as carbon sources revealed several unexpected
      fermentation products, suggesting novel metabolic capacities and unexplored
      metabolic pathways in this organism. Both 1H and 13C nuclear magnetic resonance
      (NMR) spectroscopy were used to determine intracellular and extracellular
      metabolite profiles. One dimensional 1H NMR spectral analysis was performed by
      curve fitting against spectral libraries provided in the Chenomx software; 2-D
      homonuclear and heteronuclear NMR experiments were conducted to further reduce
      uncertainties due to unassigned, overlapping, or poorly-resolved peaks. In
      addition to expected metabolites such as acetate, lactate, glycerol, and ethanol,
      several novel fermentation products were identified: ethylene glycol (from growth
      on D-arabinose), acetoin and 2,3-butanediol (from growth on D-glucose, L
      arabinose, and D-xylose), and hydroxyacetone (from growth on D-mannose, L
      arabinose, and D-xylose). Production of ethylene glycol from D-arabinose was
      particularly notable, with around 10% of the substrate carbon converted into this
      uncommon fermentation product. CONCLUSIONS: The present research shows that C.
      saccharolyticus, already of substantial interest due to its capability for
      biological ethanol and hydrogen production, has further metabolic potential for
      production of higher molecular weight compounds, such as acetoin and 2,3
      butanediol, as well as hydroxyacetone and the uncommon fermentation product
      ethylene glycol. In addition, application of nuclear magnetic resonance (NMR)
      spectroscopy facilitates identification of novel metabolites, which is
      instrumental for production of desirable bioproducts from biomass through
      microbial fermentation.

PMID- 23552327
TI  - Economic impact of switching to fixed-dose combination therapy for Japanese
      hypertensive patients: a retrospective cost analysis.
AB  - BACKGROUND: The prescription of fixed-dose combinations (FDC) of antihypertensive
      drugs has increased rapidly since the relaxation of the prescription-term
      restriction. In this study, we used the opportunity of this policy change in
      Japan as an instrument to assess the causal impact of switching to FDC on
      hypertensive treatment costs. METHODS: Claims data from 64 community pharmacies
      located in Tokyo were used to identify hypertensive patients under continuous
      treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC
      between December 2010 and April 2011 were compared to patients who did not
      receive FDC (control group). Changes in annual antihypertensive drug costs were
      compared using a difference-in-differences approach to adjust for patient
      characteristics and use of concomitant medication. Subpopulation analyses were
      also performed, taking into account pre-index treatment patterns and prescribers'
      characteristics. RESULTS: There were 542 patients who switched to FDC and 9664
      patients in the control group. No significant differences were observed between
      the 2 groups, except for antihypertensive drug use patterns before the policy
      change and prescribers' characteristics. The switch to FDC was associated with an
      annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs.
      Approximately 20% of the FDC patients, however, switched from ARB alone, and
      their drug costs increased by 2376 yen (US$25.5). CONCLUSIONS: For hypertensive
      patients who required ARB-based combination therapy, switching to FDC drugs had a
      significant cost-saving effect. However, the policy change of relaxing the
      prescription-term restriction could encourage aggressive treatment, i.e.,
      switching to a combination therapy from monotherapy, regardless of medical
      conditions. Further research is required to evaluate the possible negative
      aspects of FDC drugs.

PMID- 23552328
TI  - Old foe in modern day endovascular aortic repair.

PMID- 23552329
TI  - Ultrasonographic findings of neuroma formation at both divisions of the sciatic
      nerve in a transfemoral amputee.

PMID- 23552330
TI  - The beneficial role of intensive exercise on Parkinson disease progression.
AB  - In the last decade, a considerable number of articles has shown that exercise is
      effective in improving motor performance in Parkinson disease. In particular,
      recent studies have focused on the efficacy of intensive exercise in achieving
      optimal results in the rehabilitation of patients with Parkinson disease. The
      effects of intensive exercise in promoting cell proliferation and neuronal
      differentiation in animal models are reported in a large cohort of studies, and
      these neuroplastic effects are probably related to increased expression of a
      variety of neurotrophic factors. The authors outline the relation between
      intensive exercises and neuroplastic activity on animal models of Parkinson
      disease and discuss the clinical results of different intensive strategies on
      motor performance and disease progression in patients with Parkinson disease.

PMID- 23552331
TI  - Acute hospitalization of the older patient: changes in muscle strength and
      functional performance during hospitalization and 30 days after discharge.
AB  - OBJECTIVE: Acute hospitalization of older patients may be associated with loss of
      muscle strength and functional performance. The aim of this study was to
      investigate the effect of acute hospitalization as a result of medical disease on
      muscle strength and functional performance in older medical patients. DESIGN:
      Isometric knee-extension strength; handgrip strength; and functional performance,
      that is, the Timed Up and Go test, were assessed at admission, at discharge, and
      30 days after discharge. Twenty-four-hour mobility was measured during
      hospitalization. RESULTS: The mean (SD) age was 82.7 (8.2) years, and the median
      length of stay was 7.5 days (interquartile range, 4.25-11). Knee-extension
      strength did not change over time (1.0 [N.m]/kg, 1.1 [N.m]/kg, and 1.1 [N.m]/kg,
      P = 0.138), as did handgrip strength (24.2 kg, 23.3 kg, and 23.5 kg, P = 0.265).
      The Timed Up and Go test improved during hospitalization, from 17.3 secs at
      admission to 13.3 secs at discharge (P = 0.003), but with no improvement at the
      30-day follow-up (12.4 secs, P = 0.064). The median times spent in lying,
      sitting, and standing/walking were 17.4 hrs per day, 4.8 hrs per day, and 0.8 hrs
      per day, respectively. CONCLUSIONS: Muscle strength did not change during
      hospitalization and 30 days after discharge in the acutely admitted older medical
      patients. Despite a low level of mobility during hospitalization, functional
      performance improved significantly during hospitalization, without further
      improvement.

PMID- 23552332
TI  - Acute effect of whole-body vibration at optimal frequency on muscle power output
      of the lower limbs in older women.
AB  - OBJECTIVE: The aim of this study was to identify the frequency of whole-body
      vibration (WBV) that elicits the greatest improvement in lower limb power output
      after an acute exposure in older women, with the hypothesis that an
      individualized optimal vibration frequency (OVF) would be more effective than a
      fixed vibration frequency. DESIGN: Maximal power output was measured during a
      double leg press on an isoinertial dynamometer in nine women with a mean (SD) age
      of 71 (3) yrs, 1 and 5 mins after WBV on a platform at three different
      frequencies, in a random order: 20 Hz, 50 Hz, and OVF, determined for each
      subject by identifying the frequency corresponding to the maximal
      electromyographic muscle response. RESULTS: The mean (SD) OVF was 33 (2.5) Hz.
      The 25.9% increase in maximal power output after 1 min of WBV at OVF was
      significantly higher (P < 0.05) than the 14.3% increase after 1 min of WBV at 20
      Hz. Similarly, the 32.1% increase in maximal power output after 5 mins of WBV at
      OVF was significantly higher (P < 0.01) than the 16.1% and 16.3% increase after 5
      mins of WBV at 20 Hz and 50 Hz, respectively. CONCLUSIONS: Frequency of WBV
      should be prescribed in an individualized fashion, within the range of 30-35 Hz
      in this target population of older women.

PMID- 23552333
TI  - Reporting of allocation method and statistical analyses that deal with
      bilaterally affected wrists in clinical trials for carpal tunnel syndrome.
AB  - The authors aimed to describe how often the allocation method and the statistical
      analyses that deal with bilateral involvement are reported in clinical trials for
      carpal tunnel syndrome and to determine whether reporting has improved over time.
      Forty-two trials identified from recently published systematic reviews were
      assessed. Information about allocation method and statistical analyses was
      obtained from published reports and trialists. Only 15 trialists (36%) reported
      the method of random sequence generation used, and 6 trialists (14%) reported the
      method of allocation concealment used. Of 25 trials including participants with
      bilateral carpal tunnel syndrome, 17 (68%) reported the method used to allocate
      the wrists, whereas only 1 (4%) reported using a statistical analysis that
      appropriately dealt with bilateral involvement. There was no clear trend of
      improved reporting over time. Interventions are needed to improve reporting
      quality and statistical analyses of these trials so that these can provide more
      reliable evidence to inform clinical practice.

PMID- 23552334
TI  - Effectiveness of extracorporeal shock wave therapy in chronic plantar fasciitis:
      a meta-analysis.
AB  - The objective of this study was to evaluate the effectiveness of extracorporeal
      shock wave therapy (ESWT) in treating chronic plantar fasciitis. An online
      database search was conducted for studies using ESWT in managing chronic plantar
      fasciitis. Eleven high-quality randomized controlled trials were included in the
      meta-analysis and showed that ESWT was more effective in reducing morning pain
      (weighted mean difference, -0.77 [95% confidence interval {CI}, -1.30 to -0.25];
      odds ratio, 0.65 [95% CI, 0.42-1.00]). Moderate-intensity ESWT was more effective
      in decreasing overall and activity pain (weighted mean difference, -6.6 [95% CI, 
      6.74 to -6.46], and weighted mean difference, 0.47 (95% CI, 0.30-0.74). Both
      moderate- and high-intensity ESWT were more effective in improving functional
      outcome, with odds ratios of 0.51 (95% CI, 0.30-0.84) and 0.47 (95% CI, 0.29
      0.75). The adverse effects that were seen more in ESWT were pain on the calcaneal
      area and calcaneal erythema. This study concludes that moderate- and high
      intensity ESWT were effective in the treatment of chronic plantar fasciitis.

PMID- 23552335
TI  - Feasibility of a virtual exercise coach to promote walking in community-dwelling
      persons with Parkinson disease.
AB  - OBJECTIVE: The short-term benefits of exercise for persons with Parkinson disease
      (PD) are well established, but long-term adherence is limited. The aim of this
      study was to explore the feasibility, acceptability, and preliminary evidence of
      the effectiveness of a virtual exercise coach to promote daily walking in
      community-dwelling persons with Parkinson disease. DESIGN: Twenty subjects with
      Parkinson disease participated in this phase 1, single-group, nonrandomized
      clinical trial. The subjects were instructed to interact with the virtual
      exercise coach for 5 mins, wear a pedometer, and walk daily for 1 mo. Retention
      rate, satisfaction, and interaction history were assessed at 1 mo. Six-minute
      walk and gait speed were assessed at baseline and after the intervention.
      RESULTS: Fifty-five percent of the participants were women, and the mean age was
      65.6 yrs. At the study completion, there was 100% retention rate. The subjects
      had a mean satisfaction score of 5.6/7 (with 7 indicating maximal satisfaction)
      with the virtual exercise coach. Interaction history revealed that the
      participants logged in for a mean (SD) of 25.4 (7) days of the recommended 30
      days. The mean adherence to daily walking was 85%. Both gait speed and the 6-min
      walk test significantly improved (P < 0.05). No adverse events were reported.
      CONCLUSIONS: Sedentary persons with Parkinson disease successfully used a
      computer and interacted with a virtual exercise coach. Retention, satisfaction,
      and adherence to daily walking were high for 1 mo, and significant improvements
      were seen in mobility.

PMID- 23552336
TI  - Management of the extrahepatic symptoms of chronic hepatitis C: feasibility of a
      randomized controlled trial of exercise.
AB  - OBJECTIVE: The aim of this study was to explore the feasibility and the efficacy
      of a physiotherapy-led exercise program in changing the health status of a sample
      of patients with chronic hepatitis C. DESIGN: A single-blind randomized
      controlled trial was conducted in a sample of patients with iatrogenically
      acquired hepatitis C in Ireland. Twenty-two participants were recruited and
      randomly assigned to exercise (n = 10) and control (n = 12) groups. Both groups
      received a generic exercise advice leaflet, and the exercise group attended 12
      exercise sessions for 6 wks. A battery of physical performance measures and
      patient-reported outcome measures were assessed at baseline and 6 wks, with 1-yr
      follow-up of the self-reported measures. RESULTS: Significant group by time
      interactions during the 6-wk period were found for pain (F(1,20) = 5.15, P =
      0.034), grip strength (F(1,20) = 5.94, P = 0.024), aerobic capacity (F(1,20) =
      5.73, P = 0.024), and depression (F(1,20) = 6.16, P = 0.022), with the exercise
      group showing greater positive change. The exercise group also had superior gains
      in the 36-Item Short-Form Health Survey vitality and social function scores (P <
      0.05). The short-term gains were not sustained at 1 yr. CONCLUSIONS: This pilot
      study shows the feasibility of exercise in hepatitis C management, improving
      physical fitness, psychologic function, and quality-of-life without worsening
      symptoms in the short term.

PMID- 23552337
TI  - Examining the influence of three types of social support on the mental health of
      mexican caregivers of individuals with traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to examine the influence of three types of
      social support (appraisal, belonging, and tangible) on caregiver mental health
      (anxiety, burden, depression, and satisfaction with life) among Mexican
      caregivers of individuals with traumatic brain injury. DESIGN: This is a cross
      sectional study of 90 family caregivers from Hospital Civil Fray Antonio Alcade
      in Guadalajara, Mexico. RESULTS: More months spent caregiving was associated with
      decreases in all three types of social support. Older age and fewer years of
      education were associated with lower appraisal social support. More hours per
      week spent caregiving was associated with lower caregiver state anxiety and
      greater satisfaction with life. Appraisal, belonging, and tangible social support
      were all significantly correlated with more salubrious caregiver mental health
      outcomes, except satisfaction with life. Appraisal social support independently
      predicted lower caregiver depression. CONCLUSIONS: Particularly in Latin America,
      strong social support networks and family connections seem closely tied to key
      mental health outcomes such as depression. Rehabilitation interventions aimed at
      strengthening perceptions of social support of caregivers of individuals with
      traumatic brain injury that specifically target availability of advice may
      improve mental health and contribute to more optimal informal care for
      individuals with traumatic brain injury.

PMID- 23552338
TI  - Influence of dual-task constraints on whole-body organization during walking in
      children who are overweight and obese.
AB  - OBJECTIVE: The aim of this study was to examine the influence of dual-task
      constraints on movement and force control in children who are overweight and
      obese. DESIGN: Twelve children who are overweight and obese (4-12 yrs old) and 12
      age-matched children with normal weight participated. The children walked along a
      path at a self-selected pace under two conditions: walking carrying nothing
      (baseline condition) and walking while carrying a box (dual-task condition).
      RESULTS: The overweight/obese group showed less normalized hand vertical motion
      and shoulder range of motion compared with the control group (all P's < 0.05).
      However, in comparison with the baseline condition, the overweight/obese group
      decreased gait velocity and stride length and increased step width, lateral hand
      movement, lateral spine movement, and medial/lateral ground reaction force during
      the dual-task condition (all P's < 0.05). CONCLUSIONS: These findings indicate
      that children who are overweight and obese modify lateral movements and force
      organization when faced with dual-task constraints, which may influence their
      ability to maintain safety when dual tasking is required.

PMID- 23552340
TI  - Performance effects of 6 weeks of aerobic production training in junior elite
      soccer players.
AB  - This study investigates the performance effects of a 6-week biweekly anaerobic
      speed endurance production training among junior elite soccer players. Sixteen
      junior (age 16.9 +/- 0.6 years) elite soccer players were tested in the Yo-Yo
      Intermittent Recovery test level 2 (IR2), 10-m and 35-m sprints, 7 * 35-m
      repeated-sprint ability (RSA) tests, countermovement jump and squat jump tests,
      and randomly assigned to either a control group (CG) performing their normal
      training schedule, which included 4 weekly soccer training sessions of
      approximately 90 minutes, or a training group performing anaerobic speed
      endurance production training twice weekly for 6 weeks in addition to their
      normal weekly schedule. We found that the intervention group significantly
      improved (p < 0.05) their performance in the Yo-Yo IR2 (63 +/- 74 m) and 10-m
      sprint time (-0.06 +/- 0.06 seconds). No significant performance changes were
      found in the CG. Between-group pretest to posttest differences were found for 10
      m sprint times (p < 0.05). No significant changes were observed in the 35-m
      sprint times, RSA, or jump performances. These results indicate that short-term
      anaerobic production training is effective in improving acceleration and
      intermittent exercise performance among well-trained junior elite players.

PMID- 23552339
TI  - Microvolt T wave alternans in adults with congenital heart diseases characterized
      by right ventricle pathology or single ventricle physiology: a case control
      study.
AB  - BACKGROUND: Among adults with congenital heart diseases (CHD) evaluation of
      sudden cardiac death (SCD) risk remains a great challenge. Although microvolt T
      wave alternans has been incorporated into SCD risk stratification algorithm, its
      role in adults with CHD still requires investigation. We sought to determine the
      incidence of MTWA in this specific group and its coincidence with ventricular
      arrhythmia (VA) and other clinical findings presumably associated with SCD.
      METHODS: A case-control study was performed in which 102 patients with CHD
      characterized by right ventricle pathology or single ventricle physiology (TGA,
      UVH, Ebstein's anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated ToF)
      were compared to 45 age- and sex-matched controls. All subjects underwent
      spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP
      assessment. After excluding technically inadequate traces, the remaining MTWA
      results were classified as positive(+), negative(-) and indeterminate(ind). Due
      to similar prognostic significance MTWA(+) and (ind) were combined into a common
      group labeled 'abnormal'. RESULTS: Abnormal MTWA was present more often in the
      study group, compared to controls (39.2% vs 2.3%, p = 0.00001). Sustained
      ventricular tachycardia (sVT) was observed more often among subjects with
      abnormal MTWA compared to MTWA(-): 19.4% vs 3.6%, p = 0.026. The patients with
      abnormal MTWA had a lower blood saturation (p = 0.047), more often were males (p
      = 0.031), had higher NYHA class (p = 0.04), worse cardiopulmonary parameters:
      %PeakVO2 (p = 0.034), %HRmax (p = 0.003). Factors proven to increase probability
      of abnormal MTWA on multivariate linear regression analysis were: sVT (OR = 20.7,
      p = 0.037) and male gender (OR = 15.9, p = 0.001); on univariate analysis: male
      gender (OR = 2.7, p = 0.021), presence of VA (OR = 2.6, p = 0.049), NYHA > I (OR
      = 2.06, p = 0.033), %HRmax (OR = 0.94, p = 0.005), %PeakVO2 (OR = 0.97, p =
      0.042), VE/VCO2slope (OR = 1.05, p = 0.037). CONCLUSIONS: Abnormal MTWA occurs
      significantly more often in adults with the chosen forms of CHD than among
      healthy subjects. The probability of abnormal MTWA increases in patients with
      malignant VA, in males and among subjects with heart failure and cyanosis. MTWA
      might be of potential role in risk stratification for SCD in adults with CHD.

PMID- 23552341
TI  - Biomechanical analysis of squat jump and countermovement jump from varying
      starting positions.
AB  - The purpose of this study was to investigate the effect of 2 strategies, defined
      by foot placement during the initiation of the take-off on performance in
      vertical jumps. The additional area of interest in this experiment was whether
      technique of the take-off phase might be an exploratory factor that has different
      electromyogram (EMG) muscle activity during squat jump (SJ) and countermovement
      jump (CMJ) performed starting from the standard position, with parallel foot
      placement, and from the experimental one, with straddle foot placement. Six well
      experienced male 100-400 m sprinters, who were members of the Polish youth and
      senior national team (mean values: age 21.6 years, best performance: 100 m in
      10.54 seconds and 400 m in 45.54 seconds), performed vertical SJ and vertical CMJ
      from 2 initial positions with different foot placement. To collect all selected
      kinematic and kinetic data, the video recording system BTS Vixta was used in
      conjunction with force platforms (Kistler model 9286B). The latest system for 3D
      motion analysis, BTS SMART, based on the passive IR reflective markers was also
      applied. Electromyograms of 6 lower limb muscles were collected using a Noraxon
      EMG device. The CMJ was on average 7 cm higher than the SJ (CMJ, 85 cm and SJ, 78
      cm), which amounts to 8.97%. This was not because of the increase of center of
      gravity (COG) velocity at take-off because velocities of center of gravity (COG)
      projection were almost equal (SJ, 2.93 m.scompared with CMJ, 2.99 m.s). No
      significant differences of both magnitude and rate of development of the muscle
      torques and powers between jumps were found, but when we analyzed the problem
      with division into single legs (right and left) and with division into different
      jumps (SJ and CMJ), the differences were evident. The profiles of EMG activity of
      selected muscles showed some differences between SJ and CMJ. The vertical SJ and
      CMJ performance measurement may be of value to coaches and conditioning
      specialists who wish to develop or assess the power ability of lower extremities
      either unilaterally (single leg) or bilaterally (sum of both legs).

PMID- 23552342
TI  - Colour due to Cr3+ ions in oxides: a study of the model system MgO:Cr3+.
AB  - Seeking to understand why the cubic centre in MgO:Cr(3+) has the same 10Dq value
      as emerald, ab initio cluster and periodic supercell calculations have been
      performed. It is found that the equilibrium Cr(3+)-O(2-) distance, R, in
      MgO:Cr(3+) is equal to 2.03 A and thus 0.06 A higher than that measured for the
      emerald. Calculations carried out on the isolated CrO(6)(9-) complex at R = 2.03
      A give 10Dq = 14,510 cm(-1), which is 10% smaller than the experimental figure
      for MgO:Cr(3+). Nevertheless, when the internal electric field, ER(r), due to the
      rest of the lattice ions is also taken into account, the calculated 10Dq = 16,210
      cm(-1) coincides with the experimental value. Accordingly, the colour shift for
      different oxides doped with Cr(3+) can be well understood on the basis of this
      extrinsic contribution to 10Dq usually ignored in a ligand field description. The
      calculated electrostatic potential, VR(r), related to ER(r), is found to be
      attractive when the electronic density is lying along <110> directions and |r| >
      1 A driven by the first shell of twelve Mg(2+) ions. The action of VR(r) upon the
      CrO(6)(9-) complex slightly decreases the energy of t2g(xy,xz,yz) orbitals with
      respect to that for eg(3z(2) - r(2),x(2) - y(2)) orbitals, thus enhancing the
      10Dq value by 0.2 eV. However, the addition of VR(r) induces very small changes
      in the electronic density, a relevant fact that is related to the (2)E(t(2g)(3)) 
      > (4)A(2)(t(2g)(3)) emission energy being nearly independent of the host lattice
      along the series of Cr(3+)-doped oxides.

PMID- 23552343
TI  - Unique microbiology of chronically unstable canal wall down tympanomastoid
      cavities: considerations for surgical revision.
AB  - OBJECTIVE: To review the microbiology of open tympanomastoid cavities in patients
      who underwent revision surgery due to chronic instability. METHODS: This paper
      describes a retrospective chart review of surgical revision cases of chronically
      unstable open mastoid cavities. Patient records from 2000 to 2010 were reviewed
      for the type of organism cultured, antimicrobial resistance and the presence of
      cholesteatoma. RESULTS: In total, 121 revision surgical procedures were performed
      on 101 patients. Seventy-nine procedures involved culture specimen processing, 37
      of which were positive. The most commonly cultured organism was Staphylococcus
      aureus, which was more than twice as common as any other pathogen. The presence
      of cholesteatoma had no impact on the likelihood of a positive culture or
      polymicrobial culture. Antimicrobial-resistant pathogens were uncommon.
      CONCLUSION: A positive culture was not an overwhelmingly common characteristic of
      unstable tympanomastoid cavities. Furthermore, antimicrobial resistance did not
      appear to play an essential role in leading patients towards revision open
      mastoid surgery.

PMID- 23552344
TI  - New insights into the aspects of pulmonary diffusing capacity in Fontan patients.
AB  - BACKGROUND: Patients with a functionally univentricular heart, palliated a.m.
      Fontan, consequently have non-pulsatile pulmonary blood flow and are known to
      have a reduced pulmonary diffusing capacity. However, the cause of this reduction
      remains unclear. We aimed to assess the possible determinants in the aetiology of
      a reduced diffusing capacity and also to assess whether it could be increased.
      Furthermore, we aimed to search for predictors of a reduced diffusing capacity.
      MATERIAL AND METHODS: A total of 87 Fontan patients (mean age 16.3 +/- 7.6 years)
      performed advanced pulmonary function tests and maximal cycle ergometer tests. A
      total of 10 Fontan patients and nine matched controls performed a supine
      pulmonary function test after a supine rest. RESULTS: In the sitting pulmonary
      function test, the mean z-scores were: diffusing capacity, 2.38 +/- 1.20;
      pulmonary capillary blood volume, 2.04 +/- 0.80; and alveolar capillary membrane
      diffusing capacity, 0.14 +/- 0.84. In the supine compared with the sitting
      pulmonary function test, the diffusing capacity increased by 51.7 +/- 11.9% in
      the Fontan group and by 23.3 +/- 17.7% in the control group (p < 0.001);
      moreover, the pulmonary capillary blood volume increased by 48.3 +/- 17.4% in the
      Fontan group and by 20.2 +/- 13.9% in the control group (p = 0.001). In a
      multiple linear regression analysis including the explanatory variables of
      surgical data and exercise data at rest and peak exercise, the resting cardiac
      index was an independent predictor of the diffusing capacity (regression
      coefficient: 0.18, p < 0.001). CONCLUSIONS: The pulmonary diffusing capacity was
      reduced in Fontan patients because of a reduced pulmonary capillary blood volume,
      whereas the alveolar capillary membrane diffusing capacity was preserved. The
      diffusing capacity was highly increasable in Fontan patients compared with
      controls, and the resting cardiac index was an independent predictor of the
      diffusing capacity.

PMID- 23552345
TI  - Accounting for variability among individual pigs in deterministic growth models.
AB  - Inclusion of variation in deterministic nutritional models for growth by
      repeating simulations using different sets of parameters has been performed in
      literature without or with only hypothetic consideration of the covariance
      structure among parameters. However, a description of the structure of links
      among parameters describing individuals is required to generate realistic sets of
      parameters. In this study, the mean and covariance structure of model parameters
      describing feed intake and growth were analyzed from 10 batches of crossbred
      gilts and barrows. Data were obtained from different crossbreeds, originating
      from Large White * Landrace sows and nine sire lines. Pigs were group-housed (12
      pigs/pen) and performance testing was carried out from 70 days of age to ~110 kg
      BW. Daily feed intake (DFI) was recorded using automatic feeding stations and BW
      was measured at least every 3 weeks. A growth model was used to characterize
      individual pigs based on the observed DFI and BW. In this model, a Gompertz
      function was used to describe protein deposition and the resulting BW gain. A
      gamma function (expressing DFI as multiples of maintenance) was used to express
      the relationship between DFI and BW. Each pig was characterized through a set of
      five parameters: BW70 (BW at 70 days of age), B(Gompertz) (a precocity parameter)
      PDm (mean protein deposition rate) and DFI50 and DFI100 (DFI at 50 and 100 kg BW,
      respectively). The data set included profiles for 1288 pigs for which no eating
      or growth disorders were observed (e.g. because of disease). All parameters were
      affected by sex (except for BW70) and batch, but not by the crossbreed (except
      for PDm). An interaction between sex and crossbreed was observed for PDm (P <
      0.01) and DFI100 (P = 0.05). Different covariance matrices were computed
      according to the batch, sex, crossbreed, or their combinations, and the
      similarity of matrices was evaluated using the Flury hierarchy. As covariance
      matrices were all different, the unit of covariance (subpopulation) corresponded
      to the combination of batch, sex and crossbreed. Two generic covariance matrices
      were compared afterwards, with (median matrix) or without (raw matrix) taking
      into account the size of subpopulations. The most accurate estimation of observed
      covariance was obtained with the median covariance matrix. The median covariance
      matrix can be used, in combination with average parameters obtained on-farm, to
      generate virtual populations of pigs that account for a realistic description of
      mean performances and their variability.

PMID- 23552346
TI  - Management of macular epiretinal membrane secondary to accidental globe
      perforation during retrobulbar anesthesia.

PMID- 23552347
TI  - Contact lens use and its compliance for care among healthcare workers in
      Pakistan.
AB  - BACKGROUND: Poor care and hygiene of contact lens (CL) results in eye problems
      and infections. Healthcare workers have an important role in advocating correct
      lens care. OBJECTIVES: To determine the practices of CL care and the adverse
      consequences of poor CL care among healthcare workers. SETTING AND DESIGN: A
      cross-sectional study in one public and three private sector hospitals in
      Karachi, Pakistan, in 2009-2010. MATERIALS AND METHODS: We questioned 500
      healthcare workers of all ages and both sexes, who wore CL, about compliance with
      advice on care and any complications due to improper hygiene practices. Ethical
      approval was obtained. Chi-square tests were used to determine significance and p
      value less than 0.05 was considered statistically significant. RESULTS: Of the
      total CL users, 385 (77%) were females. Most (75%) respondents wore CL to correct
      myopia, whereas 54% wore CL only occasionally. Surprisingly, only 24% knew the CL
      cleaning protocol. Lens solution was changed daily by 33% of users and after more
      than 2 weeks by 42%. Although 412 (82%) participants practised reasonable hand
      hygiene before inserting CL, 88 (18%) did not. Infection and eye dryness were
      statistically significantly (P < 0.01) associated with sex, hand-washing, and
      frequency of CL use. CONCLUSION: Noncompliance with the CL protocol was common
      among healthcare workers in our society. This behavior calls for targeted health
      education and awareness programs for healthcare workers.

PMID- 23552348
TI  - The relationship between binocular vision symptoms and near point of convergence.
AB  - AIM AND BACKGROUND: Due to the relatively high prevalence of binocular vision
      anomalies, a regular examination including tests for assessment and determination
      of these anomalies is necessary. The aim of this study was to assess the
      relationship between near point of convergence (NPC) and near binocular vision
      symptoms and finding of an NPC cutoff point for symptoms in university students.
      MATERIALS AND METHODS: In this cross-sectional study, 124 students of different
      majors of Zahedan University of Medical Sciences were randomly selected. If they
      met the inclusion criteria, they were divided into two groups (symptomatic and
      asymptomatic) according to the convergence insufficiency symptom survey
      questionnaire. For NPC measurement, a small isolated letter "E" of approximately
      20/30 size on a metal rod was used. After data collection, data were analyzed in
      SPSS.17 software (SPSS for Windows, SPSS Inc., Chicago, IL) using descriptive and
      analytical statistics, including Mann-Whitney U test and receiver operating
      characteristic (ROC) curve. RESULTS: The mean NPC findings in the symptomatic and
      asymptomatic groups were 11.7 +/- 5.0 and 8.4 +/- 3.4 cm, respectively, with a
      significant difference between the two groups (P < 0.001). The ROC curve suggests
      an NPC cutoff point of 9.5 cm for the presence of symptoms with the testing
      procedures used in this study. Conclusion : The determination of NPC is helpful
      in the differentiation of symptomatic from asymptomatic subjects.

PMID- 23552349
TI  - Supraciliary contraction segments: a new method for the treatment of presbyopia.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the safety and effectiveness of
      supraciliary contraction segment implants (SCSIs) for the treatment of
      presbyopia. MATERIALS AND METHODS: This prospective, non-comparative study
      comprised 10 eyes from five phakic and emmetropic 50-year-old subjects.
      Preoperative and postoperative near and distance visual acuity, topography, axial
      length, pachymetry, and intraocular pressure were analyzed. A 5.32-mm long and
      0.85-mm thick piece of polymethyl methacrylat (PMMA) and a 5.32-mm long or 0.55
      mm thick dried hydrophilic SCSI were placed within the scleral tunnels that were
      created 2 mm away from the limbus. The 500-550 m deep tunnels were parallel to
      the limbus and four segments were implanted per eye. The SCSIs were entirely
      placed at a depth of approximately 85% in the sclera. RESULTS: The uncorrected
      distance visual acuity was similar before and after the surgery (0.00 logMAR).
      The monocular mean uncorrected near visual acuity (UNVA) was 0.5 +/- 0.0 before
      surgery, 0.12 +/- 0.10 logMAR at 1 month after surgery, 0.16 +/- 0.18 logMAR at 3
      months after surgery, and 0.29 +/- 0.16 logMAR at the 18-month follow-up.
      CONCLUSION: Despite obtaining satisfactory results at 6 months after the surgery,
      a follow-up of the SCSI intervention at 18 months revealed a regression of the
      early post-op UNVA improvement caused by a progressive outward movement of SCSIs.

PMID- 23552351
TI  - Multi-use of single use unims: Does economic burden outweigh contamination risk?
AB  - Aim: To assess if residual drops of unims can be used after single use to cut
      down economic load. Setting: Laboratory setting. Materials and Methods: This
      study was done to determine the possibility of multi-use of such unims. Ten unims
      of Acuvail (ketorolac tromethamine 0.45%) were opened simultaneously to culture a
      single drop from each unim daily for 7 days and growth was studied at 24 h (group
      1); a similar study was done taking extra aseptic precautions (group 2), and with
      another set of 10 unims, with one drop twice a day for 3 days (group 3). Results:
      20% unims showed growth on the 1st day and 60% on the 6th day. The growth
      consisted of Staphylococcus aureus. No growth was found in the second part of the
      study. Two drops per day arm showed incremental growth from the 3 rd dose (2 nd
      day). Conclusion: Even though unims contain more than one drop, patients should
      be strictly instructed for single use of such vials because there is potential
      risk of transmitting pathogens and a serious threat to post-cataract surgery
      patients.

PMID- 23552352
TI  - Nanotechnology in ophthalmology.

PMID- 23552353
TI  - Hemicentral retinal artery occlusion in young adults.

PMID- 23552354
TI  - Bilateral misplaced three piece posterior chamber intraocular lens in anterior
      chamber with cystoid macular edema.

PMID- 23552355
TI  - Conjunctivitis due to Neisseria sicca: a case report.
AB  - We report the first case, in Medline-based literature, of conjunctivitis caused
      by gram negative diplococcus, Neisseria sicca. Although it is not widely accepted
      as such, isolation from cultures of repeated eye swab samples suggests that N.
      sicca may be a pathogen in conjunctival infections. Positive culture for this
      organism should not be readily dismissed. Such conjunctivitis responded favorably
      to treatment with netilmicin eye drops. 

PMID- 23552356
TI  - The effects of melatonin on anxiety and pain scores of patients, intraocular
      pressure, and operating conditions during cataract surgery under topical
      anesthesia.
AB  - AIMS: To evaluate the effects of melatonin premedication on anxiety and pain
      scores of patients, operating conditions, and intraocular pressure during
      cataract surgery under topical anesthesia. MATERIALS AND METHODS: Sixty patients
      were randomly assigned to receive either sublingual melatonin 3 mg or placebo 60
      min before surgery. Verbal anxiety scores and verbal pain scores, heart rate,
      systolic and diastolic blood pressure, intraocular pressure, and quality of
      operating conditions were recorded. RESULTS: Melatonin significantly reduced the
      anxiety scores (median, interquartile range) from 5 and 5-3 to 3 and 2-4 after
      premedication and to 3 and 2-3 during surgery and to 0 and 0-1 postoperatively
      before discharge from the recovery room. There were significant differences
      between two groups in anxiety scores after premedication (95% CI 3-3.5; P =
      0.023), intraoperatively (95% CI 2.5-3.5; P = 0.007), and postoperatively (95% CI
      0.5-1; P = 0.007). The surgeon reported better quality of operating conditions in
      the melatonin group (P = 0.001). No significant difference in intraoperative and
      postoperative pain scores, intraocular pressure, heart rate, and systolic and
      diastolic blood pressure between two groups was recorded. CONCLUSION: Sublingual
      melatonin premedication for patients undergoing cataract surgery under topical
      anesthesia reduced the anxiety scores in patients and provided excellent
      operating conditions.

PMID- 23552357
TI  - Comparison of serum sodium and potassium levels in patients with senile cataract
      and age-matched individuals without cataract.
AB  - AIM: The study was to analyze mean serum sodium and potassium levels in cataract
      patients and age-matched individuals without cataract. METHODS AND MATERIALS: It
      was a prospective case-control study. Individuals more than 50 years of age who
      attended our ophthalmic center in the year 2007-2010 were grouped into those
      having cataract and those without cataract. Mean serum sodium and potassium
      levels in the cataract groups were calculated and compared with the control
      group. Statistical software SPSS14 was used for statistical analysis. RESULTS:
      Mean serum sodium levels in cataract group was 135.1 meqv/l and 133 meqv/l in the
      control group. Mean potassium was 3.96 meqv/l in the case study group and 3.97
      meqv/l in controls. Mean sodium levels among cases were significantly higher than
      control group. No difference was seen in the PSC group and control. The
      difference in mean potassium among the two groups was statistically
      insignificant. CONCLUSION: Diets with high sodium contents are a risk factor for
      senile cataract formation and dietary modifications can possibly reduce the rate
      of progression cataract.

PMID- 23552358
TI  - Coculture of autologous limbal and conjunctival epithelial cells to treat severe
      ocular surface disorders: long-term survival analysis.
AB  - BACKGROUND: Cultivated limbal epithelium for reconstruction of corneal surface is
      a well-established procedure; however, it is not adequate for damage which also
      extensively involves the conjunctiva. In severe cases of ocular surface damage
      that warrant additional conjunctival transplantation apart from cultivated limbal
      stem cell transplantation, we describe the long-term survival of a novel method
      of cocultivating autologous limbal and conjunctival epithelium on a single
      substrate. MATERIALS AND METHODS: Forty eyes of 39 patients with severe limbal
      stem cell deficiency and conjunctival scarring or symblepharon underwent
      transplantation of autologous cocultivated epithelium on human amniotic membrane.
      A ring barrier was used to segregate the central limbal and peripheral
      conjunctival epithelia in vitro. Patients were followed up at regular intervals
      to assess stability of the ocular surface, defined by absence of
      conjunctivalization into the central 4 mm of the cornea and absence of diffuse
      fluorescein staining. Penetrating keratoplasty (PKP) was subsequently performed,
      where indicated, in patients with surface stability. RESULTS: The cumulative
      survival probability was 60% at 1 year and 45% at 4 years by Kaplan-Meier
      analysis (mean follow-up duration: 33 +/- 29 months, range: 1-87 months). Best
      corrected visual acuity improved to greater than 20/200 in 38% eyes at the last
      follow-up, compared with 5% eyes before surgery. Immunohistochemistry in five of
      the corneal buttons excised for PKP showed an epithelial phenotype similar to
      cornea in all five. CONCLUSIONS: Synchronous use of cultured limbal and
      conjunctival epithelium offers a feasible alternative and a simpler one-step
      surgical approach to treat severe ocular surface disorders involving limbus and
      conjunctiva.

PMID- 23552359
TI  - Granulomatous inflammation in Acanthamoeba sclerokeratitis.
AB  - This report describes the histopathological findings in a patient with
      Acanthamoeba sclerokeratitis (ASK). A 58-year-old patient with ASK underwent
      enucleation and sections of the cornea and sclera were subjected to
      histopathology and immunohistochemistry with monoclonal mouse antihuman
      antibodies against T cell CD3 and B cell CD20 antigens. Hematoxylin and Eosin
      stained sections of the cornea revealed epithelial ulceration, Bowman's membrane
      destruction, stromal vascularization, infiltration with lymphocytes, plasma
      cells, and granulomatous inflammation with multinucleated giant cells (MNGC). The
      areas of scleritis showed complete disruption of sclera collagen, necrosis and
      infiltration with neutrophils, macrophages, lymphocytes, and granulomatous
      inflammation with MNGC. No cyst or trophozoites of Acanthamoeba were seen in the
      cornea or sclera. Immunophenotyping revealed that the population of lymphocytes
      was predominantly of T cells. Granulomatous inflammation in ASK is probably
      responsible for the continuance and progression of the scleritis and management
      protocols should include immunosuppressive agents alongside amoebicidal drugs. 

PMID- 23552360
TI  - Diagnostic accuracy of an "amended" insulin-glucose ratio for the biochemical
      diagnosis of insulinomas.

PMID- 23552361
TI  - Synthesis of cobalt aluminate nanopigments by a non-aqueous sol-gel route.
AB  - Here we report the chemical synthesis of cobalt aluminum oxide (CoAl2O4)
      nanoparticles by a non-aqueous sol-gel route. The one-pot procedure is carried
      out at mild temperatures (in the 150 to 300  degrees C range), and consists of
      the reaction between cobalt acetate and aluminium isopropoxide in benzyl alcohol.
      The resulting CoAl2O4 nanoparticles show an unusually low average size, between
      2.5 and 6.2 nm, which can be controlled by the synthesis temperature. The
      colorimetric properties of the nanoparticles are also determined by the synthesis
      temperature and the characteristic blue color of CoAl2O4 pigments is achieved in
      samples prepared at T >= 200  degrees C. The nanoparticles are
      antiferromagnetically ordered below ~27 K with an uncompensated configuration.
      The uncompensated moment shows the typical features of strongly interacting
      superparamagnetic nanoparticles and spin-glass systems.

PMID- 23552362
TI  - Oral squamous cell carcinoma in relation to field precancerisation: pathobiology.
AB  - Squamous cell carcinoma of the oral cavity evolves within a field of
      precancerized oral epithelium containing keratinocytes at different stages of
      transformation. Following acquisition of additional genetic alterations, these
      precancerous keratinocytes may become cancerous.Persons with apparently
      successfully treated oral squamous cell carcinoma are at high risk of developing
      a new carcinoma at, or close to the site of the treated tumour. This second
      carcinoma may have developed either from malignant keratinocytes left behind at
      surgery (recurrence), or from transformed keratinocytes within the field of
      precancerized epithelium from which the primary carcinoma had arisen (new
      carcinoma).The cells of the new carcinoma may have genetic changes in common with
      the cells of the original carcinoma because both are descended from a
      proliferating monoclone within the precancerized field; but if the new cancer
      originates from a different clone, it may have a dissimilar genetic profile even
      if the original and the new carcinoma are closely contiguous.The purpose of this
      article is to review the pathobiology of oral squamous cell carcinoma in relation
      to fields of precancerised oral epithelium.

PMID- 23552364
TI  - Combined experimental and theoretical investigation of the hemi-squaraine/TiO2
      interface for dye sensitized solar cells.
AB  - A simple hemi-squaraine dye (CT1) has been studied as a TiO2 sensitizer for
      application in dye sensitized solar cells (DSCs) by means of a combined
      experimental and theoretical investigation. This molecule is a prototype dye
      presenting an innovative anchoring group: the squaric acid moiety. Ab initio
      calculations based on Density Functional Theory (DFT) predict that this acid
      spontaneously deprotonates at the anatase (101) surface forming chemical bonds
      that are stronger than the ones formed by other linkers (e.g. cathecol and
      isonicotinic acid). Moreover an analysis of the electronic structure of the
      hybrid interface reveals the formation of a type II heterostructure ensuring
      adiabatic electron transfer from the molecule to the oxide. DSCs containing hemi
      squaraine dyes were assembled, characterized and their performances compared to
      state of the art cells. Experimental results (large incident photon-to-electron
      conversion efficiency and an efficiency of 3.54%) confirmed the theoretical
      prediction that even a simple hemi-squaraine is an effective sensitizer for TiO2.
      Our study paves the way to the design of more efficient sensitizers based on a
      squaric acid linker and specifically engineered to absorb light in a larger part
      of the visible range.

PMID- 23552363
TI  - Determinants and within-person variability of urinary cadmium concentrations
      among women in northern California.
AB  - BACKGROUND: Cadmium (Cd) is a toxic metal associated with increased morbidity and
      mortality. Urinary Cd (U-Cd) concentration is considered a biomarker of long-term
      exposure. OBJECTIVES: Our objectives were to evaluate the within-person
      correlation among repeat samples and to identify predictors of U-Cd
      concentrations. METHODS: U-Cd concentrations (micrograms per liter) were measured
      in 24-hr urine samples collected from 296 women enrolled in the California
      Teachers Study in 2000 and a second 24-hr sample collected 3-9 months later from
      141 of the participants. Lifestyle and sociodemographic characteristics were
      obtained via questionnaires. The Total Diet Study database was used to quantify
      dietary cadmium intake based on a food frequency questionnaire. We estimated
      environmental cadmium emissions near participants' residences using a geographic
      information system. RESULTS: The geometric mean U-Cd concentration was 0.27 ug/L
      and the range was 0.1-3.6 ug/L. The intraclass correlation among repeat samples
      from an individual was 0.50. The use of a single 24-hr urine specimen to
      characterize Cd exposure in a case-control study would result in an observed odds
      ratio of 1.4 for a true odds ratio of 2.0. U-Cd concentration increased with
      creatinine, age, and lifetime pack-years of smoking among ever smokers or
      lifetime intensity-years of passive smoking among nonsmokers, whereas it
      decreased with greater alcohol consumption and number of previous pregnancies.
      These factors explained 42-44% of the variability in U-Cd concentrations.
      CONCLUSION: U-Cd levels varied with several individual characteristics, and a
      single measurement of U-Cd in a 24-hr sample did not accurately reflect medium-
      to long-term body burden.

PMID- 23552365
TI  - Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an
      essential role of protein degradation.
AB  - BACKGROUND: n-Butanol and isobutanol produced from biomass-derived sugars are
      promising renewable transport fuels and solvents. Saccharomyces cerevisiae has
      been engineered for butanol production, but its high butanol sensitivity poses an
      upper limit to product titers that can be reached by further pathway engineering.
      A better understanding of the molecular basis of butanol stress and tolerance of
      S. cerevisiae is important for achieving improved tolerance. RESULTS: By
      combining a screening of the haploid S. cerevisiae knock-out library, gene
      overexpression, and genome analysis of evolutionary engineered n-butanol-tolerant
      strains, we established that protein degradation plays an essential role in
      tolerance. Strains deleted in genes involved in the ubiquitin-proteasome system
      and in vacuolar degradation of damaged proteins showed hypersensitivity to n
      butanol. Overexpression of YLR224W, encoding the subunit responsible for the
      recognition of damaged proteins of an ubiquitin ligase complex, resulted in a
      strain with a higher n-butanol tolerance. Two independently evolved n-butanol
      tolerant strains carried different mutations in both RPN4 and RTG1, which encode
      transcription factors involved in the expression of proteasome and peroxisomal
      genes, respectively. Introduction of these mutated alleles in the reference
      strain increased butanol tolerance, confirming their relevance in the higher
      tolerance phenotype. The evolved strains, in addition to n-butanol, were also
      more tolerant to 2-butanol, isobutanol and 1-propanol, indicating a common
      molecular basis for sensitivity and tolerance to C3 and C4 alcohols. CONCLUSIONS:
      This study shows that maintenance of protein integrity plays an essential role in
      butanol tolerance and demonstrates new promising targets to engineer S.
      cerevisiae for improved tolerance.

PMID- 23552367
TI  - Comment on "time to integrate clinical and research informatics".
AB  - The same code standards should be used in both research and clinical care to
      facilitate data integration across domains.

PMID- 23552368
TI  - Author response to comment on "time to integrate clinical and research
      informatics".
AB  - Lack of structured clinical data limits research potential of EHRs, and efforts
      to establish clinical data standards should be a priority.

PMID- 23552369
TI  - Cell-based therapeutics: the next pillar of medicine.
AB  - Two decades ago, the pharmaceutical industry-long dominated by small-molecule
      drugs-was revolutionized by the the advent of biologics. Today, biomedicine sits
      on the cusp of a new revolution: the use of microbial and human cells as
      versatile therapeutic engines. Here, we discuss the promise of this "third
      pillar" of therapeutics in the context of current scientific, regulatory,
      economic, and perceptual challenges. History suggests that the advent of cellular
      medicines will require the development of a foundational cellular engineering
      science that provides a systematic framework for safely and predictably altering
      and regulating cellular behaviors.

PMID- 23552370
TI  - Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation.
AB  - The amyloid-forming proteins tau, alphaB crystallin, and amyloid P protein are
      all found in lesions of multiple sclerosis (MS). Our previous work established
      that amyloidogenic peptides from the small heat shock protein alphaB crystallin
      (HspB5) and from amyloid beta fibrils, characteristic of Alzheimer's disease,
      were therapeutic in experimental autoimmune encephalomyelitis (EAE), reflecting
      aspects of the pathology of MS. To understand the molecular basis for the
      therapeutic effect, we showed a set of amyloidogenic peptides composed of six
      amino acids, including those from tau, amyloid beta A4, major prion protein
      (PrP), HspB5, amylin, serum amyloid P, and insulin B chain, to be anti
      inflammatory and capable of reducing serological levels of interleukin-6 and
      attenuating paralysis in EAE. The chaperone function of the fibrils correlates
      with the therapeutic outcome. Fibrils composed of tau 623-628 precipitated 49
      plasma proteins, including apolipoprotein B-100, clusterin, transthyretin, and
      complement C3, supporting the hypothesis that the fibrils are active biological
      agents. Amyloid fibrils thus may provide benefit in MS and other
      neuroinflammatory disorders.

PMID- 23552371
TI  - Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients
      with chronic graft-versus-host disease.
AB  - CD4(+)Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance
      of immune tolerance after allogeneic hematopoietic stem cell transplantation. We
      recently reported that daily administration of low-dose interleukin-2 (IL-2)
      induces selective expansion of functional Tregs and clinical improvement of
      chronic graft-versus-host disease (GVHD). To define the mechanisms of action of
      IL-2 therapy, we examined the immunologic effects of this treatment on
      homeostasis of CD4(+) T cell subsets after transplant. We first demonstrated that
      chronic GVHD is characterized by constitutive phosphorylation of signal
      transducer and activator of transcription 5 (Stat5) in conventional CD4(+) T
      cells (Tcons) associated with elevated amounts of IL-7 and IL-15 and relative
      functional deficiency of IL-2. IL-2 therapy resulted in the selective increase of
      Stat5 phosphorylation in Tregs and a decrease of phosphorylated Stat5 in Tcons.
      Over an 8-week period, IL-2 therapy induced a series of changes in Treg
      homeostasis, including increased proliferation, increased thymic export, and
      enhanced resistance to apoptosis. Low-dose IL-2 had minimal effects on Tcons.
      These findings define the mechanisms whereby low-dose IL-2 therapy restores the
      homeostasis of CD4(+) T cell subsets and promotes the reestablishment of immune
      tolerance.

PMID- 23552372
TI  - Orexin receptor antagonists differ from standard sleep drugs by promoting sleep
      at doses that do not disrupt cognition.
AB  - Current treatments for insomnia, such as zolpidem (Ambien) and eszopiclone
      (Lunesta), are gamma-aminobutyric acid type A (GABAA)-positive allosteric
      modulators that carry a number of side effects including the potential to disrupt
      cognition. In an effort to develop better tolerated medicines, we have identified
      dual orexin 1 and 2 receptor antagonists (DORAs), which promote sleep in
      preclinical animal models and humans. We compare the effects of orally
      administered eszopiclone, zolpidem, and diazepam to the dual orexin receptor
      antagonist DORA-22 on sleep and the novel object recognition test in rat, and on
      sleep and two cognition tests (delayed match to sample and serial choice reaction
      time) in the rhesus monkey. Each compound's minimal dose that promoted sleep
      versus the minimal dose that exerted deficits in these cognitive tests was
      determined, and a therapeutic margin was established. We found that DORA-22 has a
      wider therapeutic margin for sleep versus cognitive impairment in rat and rhesus
      monkey compared to the other compounds tested. These data were further supported
      with the demonstration of a wider therapeutic margin for DORA-22 compared to the
      other compounds on sleep versus the expression of hippocampal activity-regulated
      cytoskeletal-associated protein (Arc), an immediate-early gene product involved
      in synaptic plasticity. These findings suggest that DORAs might provide an
      effective treatment for insomnia with a greater therapeutic margin for sleep
      versus cognitive disturbances compared to the GABAA-positive allosteric
      modulators currently in use.

PMID- 23552373
TI  - Inertial focusing for tumor antigen-dependent and -independent sorting of rare
      circulating tumor cells.
AB  - Circulating tumor cells (CTCs) are shed into the bloodstream from primary and
      metastatic tumor deposits. Their isolation and analysis hold great promise for
      the early detection of invasive cancer and the management of advanced disease,
      but technological hurdles have limited their broad clinical utility. We describe
      an inertial focusing-enhanced microfluidic CTC capture platform, termed "CTC
      iChip," that is capable of sorting rare CTCs from whole blood at 10(7) cells/s.
      Most importantly, the iChip is capable of isolating CTCs using strategies that
      are either dependent or independent of tumor membrane epitopes, and thus
      applicable to virtually all cancers. We specifically demonstrate the use of the
      iChip in an expanded set of both epithelial and nonepithelial cancers including
      lung, prostate, pancreas, breast, and melanoma. The sorting of CTCs as unfixed
      cells in solution allows for the application of high-quality clinically
      standardized morphological and immunohistochemical analyses, as well as RNA-based
      single-cell molecular characterization. The combination of an unbiased, broadly
      applicable, high-throughput, and automatable rare cell sorting technology with
      generally accepted molecular assays and cytology standards will enable the
      integration of CTC-based diagnostics into the clinical management of cancer.

PMID- 23552374
TI  - Attenuated total reflectance infrared spectroelectrochemistry at a carbon
      particle electrode; unmediated redox control of a [NiFe]-hydrogenase solution.
AB  - We report a versatile infrared spectroscopic method for studying redox chemistry
      of metalloproteins, and demonstrate for the first time electrochemically-induced
      changes to the active site of the regulatory [NiFe]-hydrogenase from Ralstonia
      eutropha. A carbon particle network working electrode allows control over a wide
      potential window without the need for solution mediators.

PMID- 23552376
TI  - Insulin-stimulating diets during the weaning-to-estrus interval do not improve
      fetal and placental development and uniformity in high-prolific multiparous sows.
AB  - Piglet birth weight and litter uniformity are important for piglet survival.
      Insulin-stimulating sow diets before mating may improve subsequent piglet birth
      weights and litter uniformity, but the physiological mechanisms involved are not
      clear. This study evaluated effects of different levels of insulin-stimulating
      feed components (dextrose plus starch; fed twice daily) during the weaning-to
      estrus interval (WEI) on plasma insulin and IGF-1 concentrations, and on follicle
      development and subsequent luteal, fetal and placental development and uniformity
      at days 42 to 43 of pregnancy. During WEI, multiparous sows were isocalorically
      fed diets supplemented with 375 g/day dextrose plus 375 g/day corn starch (INS
      H), with 172 g/day dextrose plus 172 g/day corn starch and 144 g/day animal fat
      (INS-L), or with 263 g/day animal fat (CON). Jugular vein catheters were inserted
      through the ear vein at 1.5 days before weaning to asses plasma insulin and IGF-1
      concentrations. After estrus, all sows received a standard gestation diet until
      slaughter at days 42 to 43 of pregnancy. The dextrose plus starch-diets enhanced
      the postprandial insulin response in a dose-dependent manner (e.g. at day 2
      insulin area under the curve was 4516 MUU/444 min for CON, 8197 MUU/444 min for
      INS-L and 10 894 MUU/444 min for INS-H; s.e.m. = 694; P < 0.001), but did not
      affect plasma IGF-1 concentrations during the first 3 days of WEI. Follicle
      development and subsequent luteal, fetal and placental development and uniformity
      were not affected by the dietary treatments, nor related to plasma insulin and
      IGF-1 concentrations during WEI. Pre-weaning plasma insulin and IGF-1
      concentrations were negatively related to sow body condition loss during
      lactation, but were not related to subsequent reproduction characteristics. This
      study shows that dietary dextrose plus starch are effective in stimulating
      insulin secretion (both postprandial peak and long-term concentration), but not
      IGF-1 secretion during the first 3 days after weaning in multiparous sows. The
      extreme insulin-stimulating diets during WEI did, however, not improve follicle
      development, or subsequent development and uniformity of fetuses and placentas in
      these high-prolific sows (27.0 +/- 0.6 ovulations; 18.6 +/- 0.6 vital fetuses). 

PMID- 23552375
TI  - GeoSentinel surveillance of illness in returned travelers, 2007-2011.
AB  - BACKGROUND: International travel continues to increase, particularly to Asia and
      Africa. Clinicians are increasingly likely to be consulted for advice before
      travel or by ill returned travelers. OBJECTIVE: To describe typical diseases in
      returned travelers according to region, travel reason, and patient demographic
      characteristics; describe the pattern of low-frequency travel-associated
      diseases; and refine key messages for care before and after travel. DESIGN:
      Descriptive, using GeoSentinel records. SETTING: 53 tropical or travel disease
      units in 24 countries. PATIENTS: 42 173 ill returned travelers seen between 2007
      and 2011. MEASUREMENTS: Frequencies of demographic characteristics, regions
      visited, and illnesses reported. RESULTS: Asia (32.6%) and sub-Saharan Africa
      (26.7%) were the most common regions where illnesses were acquired. Three
      quarters of travel-related illness was due to gastrointestinal (34.0%), febrile
      (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers
      reported pretravel medical visits. The relative frequency of many diseases varied
      with both travel destination and reason for travel, with travelers visiting
      friends and relatives in their country of origin having both a disproportionately
      high burden of serious febrile illness and very low rates of advice before travel
      (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria,
      melioidosis, and African trypanosomiasis, were reported. LIMITATIONS: Sentinel
      surveillance data collected by specialist clinics do not reflect healthy
      returning travelers or those with mild or self-limited illness. Data cannot be
      used to infer quantitative risk for illness. CONCLUSION: Many illnesses may have
      been preventable with appropriate advice, chemoprophylaxis, or vaccination.
      Clinicians can use these 5-year GeoSentinel data to help tailor more efficient
      pretravel preparation strategies and evaluate possible differential diagnoses of
      ill returned travelers according to destination and reason for travel. PRIMARY
      FUNDING SOURCE: Centers for Disease Control and Prevention.

PMID- 23552378
TI  - Organised haematoma of the maxillary sinus: pathophysiological differences
      suggesting a new aetiological hypothesis.
AB  - BACKGROUND AND OBJECTIVES: Organised haematomas of the maxillary sinus are rare,
      non-neoplastic, haemorrhagic lesions which can extend into the nasal cavity
      and/or the other paranasal sinuses. This study aimed to investigate the pathology
      of maxillary sinus organised haematoma, and also proposes a new aetiological
      hypothesis based on the observed pathology. METHODS: Biopsies, computed
      tomography, magnetic resonance imaging and post-surgical histopathological
      examination of resected specimens were carried out. CONCLUSION: Distinct
      pathological differences were observed between the basal and peripheral portions
      of organised haematomas. We propose that an organised haematoma originates from
      the exudation of blood components between vascular endothelial cells. As a
      result, the basal portion consists of aggregated, dilated vessels around the
      natural ostium of the maxillary sinus. In addition, pseudovessels, without
      endothelial cells, arise from endocapillary vessels within the haematoma.
      Exudation of additional blood components from the pseudovessels advances the
      growth of the organised haematoma.

PMID- 23552379
TI  - Intestinal-type endocervical adenocarcinoma in situ: an immunophenotypically
      distinct subset of AIS affecting older women.
AB  - Conventional endocervical adenocarcinoma in situ (cAIS) is typically strongly and
      diffusely positive for p16 with a high Ki67 index consistent with its frequent
      association with high-risk human papillomavirus (HPV) infection. The intestinal
      variant (iAIS) is less common, and its relationship to HPV infection has not been
      thoroughly examined. This study compares the clinicopathologic features,
      frequency of HPV infection, and expression of CDX2 and surrogate biomarkers of
      HPV infection (p16, Ki67) in cAIS with those of iAIS. A total of 86 cases with a
      diagnosis of AIS (49 iAIS, 37 cAIS) were identified from our multi-institutional
      files. Of these, 13 iAIS and 20 cAIS cases had slides and tissue available for
      histopathologic review, immunohistochemical analysis, and molecular tests. All 86
      cases were used to evaluate clinical parameters; however, HPV DNA analysis and
      immunohistochemical analysis for p16, MIB-1, CDX2, and p53 were performed only on
      those cases with available slides or paraffin blocks. The average age at
      diagnosis was significantly higher in iAIS compared with that in cAIS (44.5 vs.
      32.6 y) (P=0.0001). All 20 cAIS cases showed moderate to strong and diffuse p16
      staining; however, only 9/13 iAIS cases showed this degree of p16 staining,
      whereas 4/13 (31%) iAIS cases showed weak and patchy distribution (P<0.02). Only
      6/9 (67%) iAIS cases were positive for either HPV type 18 (5) or 33 (1), in
      contrast to 11/11 conventional cAIS (P=0.04). Similarly, 12/14 cAIS, but only
      5/13 iAIS, cases showed a high Ki67 proliferative index. CDX2 was positive in all
      iAIS cases, whereas p53 was negative. Most iAIS cases are positive for high-risk
      HPV and show moderate to strong and diffuse p16 staining; however, a subset of
      iAIS shows variable staining with p16 and Ki67, is not associated with HPV, and
      occurs in a distinctly older age group suggesting an alternative pathogenesis.
      Awareness that iAIS can show variable staining for p16 and Ki67 is important when
      resolving problematic endocervical lesions, particularly in small biopsies with
      unusual p16 staining patterns.

PMID- 23552380
TI  - Cell cycle regulatory markers in uterine atypical leiomyoma and leiomyosarcoma:
      immunohistochemical study of 68 cases with clinical follow-up.
AB  - Cell cycle regulatory protein expression by immunohistochemical assay may have
      diagnostic utility in the distinction of uterine leiomyosarcoma from leiomyoma
      variants. p16, p21, p27, and p53 protein expression was evaluated by
      immunohistochemistry on 44 atypical leiomyomas (mean follow-up, 50.8 mo), 16
      leiomyosarcomas (mean follow-up, 29.7 mo), and 8 cellular leiomyomas (mean follow
      up, 22.6 mo). Nuclear staining was semiquantitatively scored on 1 representative
      section per case as negative (0%), focal (>0% to 33%), patchy (>33% to 66%), or
      diffuse (>66%). In addition, staining intensity was noted as weak, moderate, or
      strong. Proliferative index was gauged by Ki-67 and PHH3 immunohistochemical
      staining. One of 35 atypical leiomyoma patients with follow-up data developed an
      extrauterine recurrence 25.7 months after hysterectomy, whereas a second had
      intrauterine recurrence 24.9 months after myomectomy. Seven of 8 patients with
      leiomyosarcoma with follow-up had recurrence within the follow-up period, whereas
      there were no recurrences in patients with cellular leiomyoma. The Ki-67
      proliferation index ranged from 0% to 25% in atypical leiomyoma (mean, 2%) and 6%
      to 50% in leiomyosarcoma (mean, 25%) with 0% to 10% in cellular leiomyoma (mean,
      3%), whereas the PHH3 proliferation index ranged from 0% to 3% in atypical
      leiomyoma (mean, <1%) and 0% to 10% in leiomyosarcoma (mean, 2%) with 0% to 2% in
      cellular leiomyoma (mean, <1%). The atypical leiomyoma with extrauterine
      recurrence was diffusely positive for p21, but showed only weak focal (<33%)
      staining for all other cell cycle markers. Uterine atypical leiomyomas, cellular
      leiomyomas, and leiomyosarcomas demonstrate a heterogenous pattern of cell cycle
      regulatory protein expression. Caution should be exercised in distinguishing
      leiomyosarcoma from atypical leiomyoma variants on the basis of cell cycle
      protein expression alone. In our study, cell cycle markers were not useful for
      predicting recurrence in atypical leiomyoma.

PMID- 23552381
TI  - Atypical leiomyomas of the uterus: a clinicopathologic study of 51 cases.
AB  - Atypical leiomyoma is a well-described smooth muscle neoplasm of the uterus. Only
      1 study has addressed long-term clinical follow-up in a large series, and little
      is known about the adequacy of treatment by myomectomy. The surgical pathology
      archives were searched for consecutive cases of uterine atypical leiomyoma from
      1992 to 2003. Glass slides were reviewed to confirm the diagnoses, and patient
      age, treatment modality, and clinical follow-up data were recorded. Fifty-one
      atypical leiomyomas with available glass slides and clinical follow-up data were
      identified. Thirty tumors exhibited diffuse, moderately to severely atypical
      cells, whereas 21 showed atypical cells in a more focal or patchy distribution.
      Twelve had ischemic-type necrosis. By the highest count method, 37 cases were
      found to have <=1 MF/10 HPF, 13 showed 1 to 3 MF/10 HPF, and 1 was nearly
      entirely necrotic precluding mitotic assessment. Among cases in which adjacent
      non-neoplastic tissue was well visualized, all were found to have pushing margins
      (46 cases). The average tumor size was 6.8 cm (median 6.5 cm; range, 0.7 to 14
      cm). The average patient age was 42.5 years (median 42 y; range, 21 to 72 y). In
      all cases, the initial diagnostic procedure was hysterectomy (34) or myomectomy
      (17). Average follow-up was 42 months (range, 0.3 to 121.8 mo). Of those treated
      with hysterectomy, 1 had recurrent atypical leiomyoma in the retroperitoneum at
      87.5 months, 1 died of other causes, and the remaining 32 (94%) were free of
      disease. Of the myomectomy group, 82% had no evidence of recurrent disease on
      follow-up: 2 had residual atypical leiomyoma in the subsequent hysterectomy
      specimen; and 1 underwent second myomectomy for atypical leiomyoma with 2
      subsequent successful pregnancies. Atypical leiomyoma has a low rate of
      extrauterine, intra-abdominal recurrence (<2%) with a negligible risk for distant
      metastasis. Patients may be treated by myomectomy alone with successful
      pregnancy, but should be monitored for local intrauterine residual/recurrent
      disease.

PMID- 23552382
TI  - Interobserver variability in the interpretation of tumor cell necrosis in uterine
      leiomyosarcoma.
AB  - On the basis of the most recent World Health Organization classification,
      distinction of leiomyosarcoma (LMS) from leiomyoma is based on the presence of
      the following morphologic criteria: (1) nuclear atypia; (2) mitotic index; and
      (3) tumor cell necrosis (TCN). Unlike ischemic-type necrosis, which may be seen
      in benign and malignant smooth muscle tumors (SMTs), TCN is thought to be found
      only in LMS. The distinction between these 2 types of necrosis can be
      challenging, especially during the early stages, when necrotic foci are small, or
      when overlapping features are identified. The aim of this study is to assess the
      interobserver variability in the interpretation of TCN in uterine LMS. Thirty
      four LMS cases were retrieved, and a representative hematoxylin and eosin slide
      showing 1 area of necrosis was selected from each case. Pathologists from 6
      different institutions subspecializing in gynecologic pathology performed a
      blinded, independent review of the slides. Using the current World Health
      Organization criteria for assessment of TCN, they had to classify the necrotic
      foci into: (1) TCN; (2) no TCN; or (3) indeterminate for TCN. Agreement among
      panelists was categorized as: full-all pathologists in agreement; partial-4 or 5
      pathologists in agreement; no agreement-<=3 pathologists placing the case into
      the same category. Full agreement regarding the presence or absence of TCN was
      reached in 12 cases (35%) (7 thought to show TCN); partial agreement in 16 (47%);
      and no general consensus was obtained in 6 (18%). Overall, the level of agreement
      was moderate (kappa=0.436). In 8 of 34 instances (23.5%), >=1 pathologist made a
      diagnosis of "TCN" and >=1 pathologist made the diagnosis of "no TCN" for the
      same slide. The number of cases diagnosed as "indeterminate for TCN" by each
      pathologist ranged from 0 to 10 with a mean of 5.8. In 20 cases, at least 1
      pathologist diagnosed "indeterminate for TCN" (59%), at least 2 and 3 were
      undecided in 10 (29%) and 4 (12%) cases, respectively, and 4 pathologists
      diagnosed "indeterminate for TCN" in 1 instance. When excluding foci of necrosis
      diagnosed as "indeterminate" by any pathologist, disagreement occurred in 2/14
      (14%) cases. From these results we conclude that the level of interobserver
      agreement among expert gynecologic pathologists in the assessment of TCN in
      uterine SMTs is only moderate. These results further reiterate the importance of
      assessing for both nuclear atypia and mitotic activity when differentiating
      between benign and malignant SMTs and not relying solely on the presence of TCN.

PMID- 23552383
TI  - p16 is superior to ProEx C in identifying high-grade squamous intraepithelial
      lesions (HSIL) of the anal canal.
AB  - Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is
      increasing, interobserver and intraobserver reproducibility in the grading of
      biopsy specimens from this area remains unacceptably low. Attempts to produce a
      more reproducible grading scheme have led to the use of biomarkers for the
      detection of high-risk HPV (HR-HPV). We evaluated the performance of standard
      morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17
      nondysplastic lesions, 23 low-grade squamous intraepithelial lesions
      (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15
      invasive squamous cell carcinomas] from the anal and perianal region in 65
      patients and correlated these findings with HPV subtype on the basis of a type
      specific multiplex real-time polymerase chain reaction assay designed to detect
      HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was
      typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast,
      only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of
      LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the
      majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which
      were accurately labeled by strong and diffuse block-positive p16 and ProEx C,
      respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most
      harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16
      outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67
      was also increased in HR-HPV-positive lesions, although biopsies with increased
      inflammation and reactive changes also showed higher Ki-67 indices. These data
      suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling
      with p16 is a highly specific biomarker for the presence of HR-HPV in anal
      biopsies and that this finding correlates with high-grade lesions.

PMID- 23552377
TI  - Molecular testing guideline for selection of lung cancer patients for EGFR and
      ALK tyrosine kinase inhibitors: guideline from the College of American
      Pathologists, International Association for the Study of Lung Cancer, and
      Association for Molecular Pathology.
AB  - OBJECTIVE: To establish evidence-based recommendations for the molecular analysis
      of lung cancers that are that are required to guide EGFR- and ALK-directed
      therapies, addressing which patients and samples should be tested, and when and
      how testing should be performed. PARTICIPANTS: Three cochairs without conflicts
      of interest were selected, one from each of the 3 sponsoring professional
      societies: College of American Pathologists, International Association for the
      Study of Lung Cancer, and Association for Molecular Pathology. Writing and
      advisory panels were constituted from additional experts from these societies.
      EVIDENCE: Three unbiased literature searches of electronic databases were
      performed to capture articles published published from January 2004 through
      February 2012, yielding 1533 articles whose abstracts were screened to identify
      521 pertinent articles that were then reviewed in detail for their relevance to
      the recommendations. Evidence was formally graded for each recommendation.
      CONSENSUS PROCESS: Initial recommendations were formulated by the cochairs and
      panel members at a public meeting. Each guideline section was assigned to at
      least 2 panelists. Drafts were circulated to the writing panel (version 1),
      advisory panel (version 2), and the public (version 3) before submission (version
      4). CONCLUSIONS: The 37 guideline items address 14 subjects, including 15
      recommendations (evidence grade A/B). The major recommendations are to use
      testing for EGFR mutations and ALK fusions to guide patient selection for therapy
      with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase
      (ALK) inhibitor, respectively, in all patients with advanced-stage
      adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk
      factors, and to prioritize EGFR and ALK testing over other molecular predictive
      tests. As scientific discoveries and clinical practice outpace the completion of
      randomized clinical trials, evidence-based guidelines developed by expert
      practitioners are vital for communicating emerging clinical standards. Already,
      new treatments targeting genetic alterations in other, less common driver
      oncogenes are being evaluated in lung cancer, and testing for these may be
      addressed in future versions of these guidelines.

PMID- 23552384
TI  - Lymphatic invasion predicts aggressive behavior in melanocytic tumors of
      uncertain malignant potential (MELTUMP).
AB  - Lymphatic invasion (LI) identified by immunohistochemical (IHC) staining is
      common in primary cutaneous melanoma, and LI has been shown to be an independent
      prognostic factor in melanoma. Its prognostic significance in melanocytic tumors
      of uncertain malignant potential (MELTUMPs) has not been well characterized. This
      study included 32 patients with provisional diagnoses of MELTUMP. Lesions were
      evaluated for tumor thickness, the presence of ulceration, mitotic figures,
      mitotic figures at the base, tumor infiltrating lymphocytes, as well as
      peritumoral and intratumoral lymphatic density. Dual IHC staining was used to
      microscopically detect lymphatic endothelium (podoplanin) containing melanoma
      cells (S100), with the aid of multispectral imaging in select cases. Univariate
      analysis was performed to identify associations between clinical and pathologic
      variables and melanoma-related events. The 32 patients had a median follow-up of
      111 months. Two patients subsequently died of melanoma-related disease, 1 died of
      unknown causes, 5 developed nodal metastases, and the remainder showed no
      evidence of progressive disease. LI was identified in 8/32 patients (25%) by dual
      IHC staining, which included the 2 patients who died of melanoma-related disease,
      1 patient with bulky nodal metastasis, 1/4 patients with microscopic nodal
      metastases, and 4 patients who showed no evidence of progressive disease. The
      presence of LI was associated with melanoma metastases or melanoma-related death
      (P=0.05). The presence of LI by dual IHC in MELTUMPs is associated with a poorer
      prognosis, specifically with melanoma metastasis, and may therefore serve as a
      useful prognostic factor for risk stratification of patients with these
      diagnostically challenging lesions.

PMID- 23552385
TI  - Epithelioid GBMs show a high percentage of BRAF V600E mutation.
AB  - BRAF V600E mutation has been identified in up to 2/3 of pleomorphic
      xanthoastrocytomas (PXAs), World Health Organization grade II, as well as in
      varying percentages of PXAs with anaplastic features (PXA-A), gangliogliomas,
      extracerebellar pilocytic astrocytomas, and, rarely, giant cell glioblastoma
      multiforme (GC-GBMs). GC-GBMs and epithelioid GBMs (E-GBMs) can be histologically
      challenging to distinguish from PXA-A. We undertook this study specifically to
      address whether these 2 tumor types also showed the mutation. We tested our
      originally reported cohort of 8 E-GBMs and 2 rhabdoid GBMs (R-GBM) as well as 5
      new E-GBMs (1 pediatric, 4 adult) and 9 GC-GBMs (2 pediatric, 7 adult) (n=24) for
      BRAF V600E mutational status. Twenty-one of 24 had sufficient material for IDH-1
      immunostaining, which is usually absent in PXAs, PXA-As, and primary GBMs but
      present in secondary GBMs. Patients ranged in age from 4 to 67 years. BRAF V600E
      mutation was identified in 7/13 of E-GBMs, including 3 of our original cases;
      patients with mutation were aged 10 to 50 years. None of the 9 GC-GBMs or 2 R
      GBMs manifested this mutation, including pediatric patients. The sole secondary E
      GBM was the single case manifesting positive IDH-1 immunoreactivity. A high
      percentage of E-GBMs manifest BRAF V600E mutation, paralleling PXAs. All R-GBMs
      and GC-GBMs were negative, although larger multi-institutional cohorts will have
      to be tested to extend this result. BRAF V600E mutational analyses should be
      performed on E-GBMs, particularly in all pediatric and young-aged adults, given
      the potential for BRAF inhibitor therapy in this subset of GBM patients.

PMID- 23552386
TI  - The impact of tumor size in breast needle biopsy material on final pathologic
      size and tumor stage: a detailed analysis of 222 consecutive cases.
AB  - Tumor size is a significant prognostic indicator for invasive mammary carcinoma.
      By current standards, this is routinely reported during pathologic evaluation of
      the definitive excision, but no recommendations exist for reporting tumor size in
      needle biopsy material. The purpose of this study is to evaluate the relationship
      between tumor size on breast needle biopsy specimens and that on subsequent
      definitive excision specimens and to evaluate the impact of the former, if any,
      in determining the final pathologic tumor stage. This was achieved by an
      evaluation of 222 consecutive cases of invasive mammary carcinoma for which both
      the diagnostic biopsy and definitive excision were available for review. Of 200
      cases without a history of neoadjuvant therapy, there were 161 (80.5%) cases in
      which the tumor size on biopsy was smaller, 15 (7.5%) cases in which the sizes
      were equal, and 24 (12%) in which the size on biopsy was greater, including 6
      (3%) cases with no residual tumor on excision. The average size change (excision
      size minus biopsy size) increased with increasing tumor stage, with these being
      significantly lower in pT1a compared with pT1b tumors (-0.14 vs. 0.17 mm;
      P=0.0002), pT1a/b compared with pT1c tumors (0.12 vs. 0.53 mm; P<0.0001), and pT1
      compared with pT2/3 tumors (0.32 vs. 2.2 mm; P<0.001). Of the 24 cases in which
      tumor size on biopsy was greater than that on excision, there were 15 (7.5% of
      cohort) in which the tumor size on biopsy was the sole determinant of a higher
      final pathologic T stage. A larger tumor size on biopsy compared with that on
      excision was significantly associated with a lower final pathologic T stage
      (P<0.001) but not with patient age, histologic type, histologic grade, mitotic
      score, or the presence/absence of ductal carcinoma in situ. Evaluation of the
      remaining 22 cases also showed that there was a clear association between a
      history of neoadjuvant therapy and the finding of a larger size on biopsy
      compared with that on excision (P<0.0001). These findings indicate that tumor
      size on breast needle biopsy is not infrequently larger than that on excision and
      can also dictate the final pathologic T stage. Accordingly, it is recommended
      that the greatest extent of invasive carcinoma is reported in all needle biopsy
      specimens.

PMID- 23552387
TI  - Adamantinoma-like Ewing family tumor of soft tissue associated with the vagus
      nerve: a case report and review of the literature.
AB  - Adamantinoma-like Ewing family tumor (EFT) is a rare subset of EFTs showing mixed
      features of Ewing sarcoma and adamantinoma of the long bones. All currently
      reported cases of the adamantinoma-like type have been associated with bone.
      Recently, a unique type of EFT was reported showing complex epithelial
      differentiation associated with the vagus nerve. Here we describe another unique
      type of EFT arising in the soft tissue of the neck associated with the vagus
      nerve. An 11-year-old girl presented to our hospital with a neck tumor on her
      right side. Surgical resection was performed, and histopathologic examination
      demonstrated a high-grade malignant neoplasm. The tumor was composed of sheets of
      small round proliferating cells, basaloid tumor nests with marked squamous
      differentiation, biphasic growth pattern with epithelioid tumor nests, and
      spindle cell proliferation. Immunohistochemically, the tumor cells showed diffuse
      expression of CD99 and FLI-1. In addition, small round cells and
      basaloid/squamoid components were immunoreactive for AE1/AE3, CAM5.2, cytokeratin
      5/6, high-molecular weight keratin, p63, and p40 (DeltaNp63). Reverse
      transcription polymerase chain reaction and direct sequencing analysis revealed
      that the tumor harbored a t(11;22) translocation, involving EWSR1 and FLI-1,
      which are characteristic of EFTs. According to these findings, our case has
      characteristics of both a subset of adamantinoma-like EFT and EFT with complex
      epithelial differentiation. We suggest that EFT with complex epithelial
      differentiation is in a common spectrum with the adamantinoma-like type and that
      adamantinoma-like EFTs can arise in soft tissue, leading to difficulty in
      differential diagnosis with malignant epithelial tumors.

PMID- 23552388
TI  - Practice gaps. Engaging patients in eczema care from planning through
      implementation.

PMID- 23552389
TI  - Integration of electrooxidative cyclization and chemical oxidation via
      alkoxysulfonium ions. Synthesis of exocyclic ketones from alkenes with
      cyclization.
AB  - An integration of electrooxidative cyclization and chemical oxidation was
      achieved. Electrochemical oxidation of alkenes having a nucleophilic moiety in
      the presence of DMSO gave cyclized alkoxysulfonium ions, which were converted to
      the corresponding ketones by treatment with triethylamine in a one-pot sequential
      manner. The method is also an effective tool for cyclization of 1,6-dienes
      affording five-membered ring diketones in high stereoselectivity.

PMID- 23552390
TI  - Brief mindfulness-based therapy for chronic tension-type headache: a randomized
      controlled pilot study.
AB  - BACKGROUND: Mindfulness-based therapy (MBT) has been demonstrated to be effective
      for reducing chronic pain symptoms; however, the use of MBT for Chronic Tension
      Type Headache (CTH) exclusively has to date not been examined. Typically, MBT for
      chronic pain has involved an 8-week program based on Mindfulness Based Stress
      Reduction. Recent research suggests briefer mindfulness-based treatments may be
      effective for chronic pain. AIMS: To conduct a pilot study into the efficacy of
      brief MBT for CTH. METHOD: We conducted a randomized controlled trial of a brief
      (6-session, 3-week) MBT for CTH. RESULTS: Results indicated a significant
      decrease in headache frequency and an increase in the mindfulness facet of
      Observe in the treatment but not wait-list control group. CONCLUSION: Brief MBT
      may be an effective intervention for CTH.

PMID- 23552391
TI  - Author reply: To PMID 23208166.

PMID- 23552392
TI  - The effect of manager exclusion on nurse turnover intention and care quality.
AB  - Little is known about how exclusionary practices (i.e., ignored, ostracized) by
      managers differ across demographics and influence nursing outcomes. This study
      examines whether managerial exclusion varies by generation, race, and gender, and
      the extent to which these variables, in turn, relate to turnover intention and
      perceived patient care among a sample of 747 nurses working in hospitals in a
      midwestern health system. Exclusion did not differ across most demographic
      groups, though men reported less exclusion than women. Younger nurses of the
      Millennial generation, those feeling excluded, and those with fewer years of
      experience reported lower quality patient care. Managerial exclusion, being a
      nurse of color, and less experience were associated with stronger intentions to
      leave. Nursing leaders should attend to factors that may contribute to racial
      minorities seeking other jobs, diminish younger nurses' ability to provide high
      quality care, and minimize practices that might lead nurses to feel excluded. 

PMID- 23552393
TI  - Understanding sample size determination in nursing research.
AB  - Sample size determination is a natural consideration in the planning stages of
      most research studies. The purpose of this work is to provide an overview of
      modern methods of sample size determination and describe some of the challenges
      to be aware of and pitfalls to avoid in applying these various methods. Although
      sample size can be determined in many ways, the most commonly used approach has
      relied on classical hypothesis-based methods of power analysis. Several
      challenges often arise with traditional power analysis. For example, the
      statistical methods used in a power analysis may not adequately address the
      complexities of the data collected in a research study. The American
      Psychological Association currently accepts and endorses the use of two methods,
      power analysis and precision estimation, for sample size determination. Precision
      estimation is a viable alternative to the traditional power analysis approach.
      Recommendations for deciding on an approach are provided. 

PMID- 23552394
TI  - De novo triplication of 11q12.3 in a patient with developmental delay and
      distinctive facial features.
AB  - BACKGROUND: Triplication is a rare chromosomal anomaly. We identified a de novo
      triplication of 11q12.3 in a patient with developmental delay, distinctive facial
      features, and others. In the present study, we discuss the mechanism of
      triplications that are not embedded within duplications and potential genes which
      may contribute to the phenotype. RESULTS: The identified triplication of 11q12.3
      was 557 kb long and not embedded within the duplicated regions. The aberrant
      region was overlapped with the segment reported to be duplicated in 2 other
      patients. The common phenotypic features in the present patient and the
      previously reported patient were brain developmental delay, finger abnormalities
      (including arachnodactuly, camptodactyly, brachydactyly, clinodactyly, and broad
      thumbs), and preauricular pits. CONCLUSIONS: Triplications that are not embedded
      within duplicated regions are rare and sometimes observed as the consequence of
      non-allelic homologous recombination. The de novo triplication identified in the
      present study is novel and not embedded within the duplicated region. In the
      11q12.3 region, many copy number variations were observed in the database. This
      may be the trigger of this rare triplication. Because the shortest region of
      overlap contained 2 candidate genes, STX5 and CHRM1, which show some relevance to
      neuronal functions, we believe that the genomic copy number gains of these genes
      may be responsible for the neurological features seen in these patients.

PMID- 23552395
TI  - Structural, microstructural and magnetic properties of (La(1-x)Ca(x))MnO3
      nanoparticles.
AB  - The crystal and magnetic structures of 10 and 20 nm sized (La1-xCax)MnO3 (x =
      0.37, 0.50, 0.75) have been investigated between 5 and 300 K by means of Rietveld
      refinement of neutron powder diffraction data, coupled with transmission electron
      microscope observation and magnetization measurements. TEM observation reveals
      that nanoparticles are strongly affected by strain fields, probably originating
      from surface pressure. Irrespective of the composition, charge and orbital
      orderings are suppressed and Fz and Cy spin orderings coexist at low temperature;
      Cy and Fz orderings likely occur within the strained regions of the nanoparticles
      and in the matrix respectively. Moreover Gz and Az orderings are sometimes
      observed, and are likely to be taking place at the border of the strained
      regions.

PMID- 23552398
TI  - Modeling CO2 reduction on Pt(111).
AB  - Density functional theory was used to model the electrochemical reduction of CO2
      on Pt(111) with an explicit solvation layer and the presence of extra hydrogen
      atoms to represent a negatively charged electrode. We focused on the electronic
      energy barriers for the first four lowest energy proton-electron transfer steps
      for reducing CO2 on Pt(111) beginning with adsorbed *CO2 and continuing with
      *COOH, *CO + H2O, *COH, and ending with *C + H2O. We find that simple elementary
      steps in which a proton is transferred to an adsorbate (such as the protonation
      of *CO to *COH) have small barriers on the order of 0.1 eV. Elementary steps in
      which a proton is transferred and a C-O bond is simultaneously cleaved show
      barriers on the order of 0.5 eV. All barriers calculated for these steps show no
      sign of being insurmountable at room temperature. To explain why these barriers
      are so small, we analyze the charge density and the density of states plots to
      see that first, the electron transfer is decoupled from the proton transfer so
      that in the initial state, the surface and adsorbate are already charged up and
      can easily accept the proton from solution. Also, we see that in the cases where
      barriers are on the order of 0.1 eV, electron density in the initial state
      localizes on the oxygen end of the adsorbate, while electron density is more
      spread out on the surface for initial states of the C-O bond cleaving elementary
      steps.

PMID- 23552397
TI  - Nutritional status of indigenous children: findings from the First National
      Survey of Indigenous People's Health and Nutrition in Brazil.
AB  - INTRODUCTION: The prevalence of undernutrition, which is closely associated with
      socioeconomic and sanitation conditions, is often higher among indigenous than
      non-indigenous children in many countries. In Brazil, in spite of overall
      reductions in the prevalence of undernutrition in recent decades, the nutritional
      situation of indigenous children remains worrying. The First National Survey of
      Indigenous People's Health and Nutrition in Brazil, conducted in 2008-2009, was
      the first study to evaluate a nationwide representative sample of indigenous
      peoples. This paper presents findings from this study on the nutritional status
      of indigenous children < 5 years of age in Brazil. METHODS: A multi-stage
      sampling was employed to obtain a representative sample of the indigenous
      population residing in villages in four Brazilian regions (North, Northeast,
      Central-West, and Southeast/South). Initially, a stratified probabilistic
      sampling was carried out for indigenous villages located in these regions.
      Households in sampled villages were selected by census or systematic sampling
      depending on the village population. The survey evaluated the health and
      nutritional status of children < 5 years, in addition to interviewing mothers or
      caretakers. RESULTS: Height and weight measurements were taken of 6,050 and 6,075
      children, respectively. Prevalence rates of stunting, underweight, and wasting
      were 25.7%, 5.9%, and 1.3%, respectively. Even after controlling for confounding,
      the prevalence rates of underweight and stunting were higher among children in
      the North region, in low socioeconomic status households, in households with
      poorer sanitary conditions, with anemic mothers, with low birthweight, and who
      were hospitalized during the prior 6 months. A protective effect of breastfeeding
      for underweight was observed for children under 12 months. CONCLUSIONS: The
      elevated rate of stunting observed in indigenous children approximates that of
      non-indigenous Brazilians four decades ago, before major health reforms greatly
      reduced its occurrence nationwide. Prevalence rates of undernutrition were
      associated with socioeconomic variables including income, household goods,
      schooling, and access to sanitation services, among other variables. Providing
      important baseline data for future comparison, these findings further suggest the
      relevance of social, economic, and environmental factors at different scales
      (local, regional, and national) for the nutritional status of indigenous peoples.

PMID- 23552396
TI  - Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA.
AB  - BACKGROUND: Altered DNA methylation has been associated with various diseases.
      OBJECTIVE: We evaluated the association between levels of methylation in
      leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non
      genetic characteristics of 892 control participants from the Spanish Bladder
      Cancer/EPICURO study. METHODS: We determined LINE-1 methylation levels by
      pyrosequencing. Individual data included demographics, smoking status, nutrient
      intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene
      variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism
      pathway. To assess the association between LINE-1 methylation levels (percentage
      of methylated cytosines) and potential determinants, we estimated beta
      coefficients (betas) by robust linear regression. RESULTS: Women had lower levels
      of LINE-1 methylation than men (beta = -0.7, p = 0.02). Persons who smoked blond
      tobacco showed lower methylation than nonsmokers (beta = -0.7, p = 0.03). Arsenic
      toenail concentration was inversely associated with LINE-1 methylation (beta = 
      3.6, p = 0.003). By contrast, iron (beta = 0.002, p = 0.009) and nickel (beta =
      0.02, p = 0.004) were positively associated with LINE-1 methylation. Single
      nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, beta = 0.3, p =
      0.002), TCN2 (rs9606756-GG, beta = 1.9, p = 0.008; rs4820887-AA, beta = 4.0, p =
      4.8 * 10-7; rs9621049-TT, beta = 4.2, p = 4.7 * 10-9), AS3MT (rs7085104-GG, beta
      = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: beta = 0.5 and CC vs. TT: beta =
      -0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: beta = 0.3 and TT vs.
      CC; beta = -0.8, global p = 0.05) were associated with LINE-1 methylation.
      CONCLUSIONS: We identified several characteristics, environmental factors, and
      common genetic variants that predicted DNA methylation among study participants.

PMID- 23552399
TI  - Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti
      polysaccharide antibody formation.
AB  - To identify rate-limiting steps in T cell-independent type 2 antibody production
      against polysaccharide antigens, we performed a genome-wide screen by immunizing
      several hundred pedigrees of C57BL/6 mice segregating N-ethyl-N-nitrosurea
      induced mis-sense mutations. Two independent mutations, Tilcara and Untied, were
      isolated that semi-dominantly diminished antibody against polysaccharide but not
      protein antigens. Both mutations resulted from single-amino-acid substitutions
      within the kinase domain of protein kinase C-beta (PKCbeta). In Tilcara, a
      Ser552>Pro mutation occurred in helix G, in close proximity to a docking site for
      the inhibitory N-terminal pseudosubstrate domain of the enzyme, resulting in
      almost complete loss of active, autophosphorylated PKCbetaI, whereas the amount
      of alternatively spliced PKCbetaII protein was not markedly reduced. Circulating
      B cell subsets were normal and acute responses to B-cell receptor stimulation
      such as CD25 induction and initiation of DNA synthesis were only measurably
      diminished in Tilcara homozygotes, whereas the fraction of cells that had divided
      multiple times was decreased to an intermediate degree in heterozygotes. These
      results, coupled with evidence of numerous mis-sense PRKCB mutations in the human
      genome, identify Prkcb as a genetically sensitive step likely to contribute
      substantially to population variability in anti-polysaccharide antibody levels.

PMID- 23552400
TI  - No association of primary Sjogren's syndrome with Fcgamma receptor gene variants.
AB  - The genetic background of primary Sjogren's syndrome (pSS) is partly shared with
      systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important
      for clearance of immune complexes. Fcgamma receptor variants and gene deletion
      have been found to confer SLE risk. In this study, four Fcgamma receptor single
      nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied.
      Swedish and Norwegian pSS patients (N=527) and controls (N=528) were genotyped
      for the Fcgamma receptor gene variant FCGR2A H131R (rs1801274) by the Illumina
      GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485
      controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and
      FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP
      genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using
      a TaqMan copy number assay. None of the SNPs showed any association with pSS.
      Also, no FCGR3B CNV association was detected. The lack of association of pSS with
      Fcgamma receptor gene variants indicates that defective immune complex clearance
      may not be as important in pSS pathogenesis as in SLE, and may point to important
      differences between SLE and pSS.

PMID- 23552401
TI  - Pinellia pedatisecta agglutinin interacts with the methylosome and induces cancer
      cell death.
AB  - Pinellia pedatisecta agglutinin (PPA) is a specific mannose-binding plant lectin
      accumulated in the tuber of P. pedatisecta. In the work presented, the
      cytotoxicity of PPA to cancer cells was investigated through exogenous
      expression. A PPA gene was transduced into normal and cancer cell lines through
      plasmid vectors, and the effect of PPA expression was examined. Results showed
      that PPA translocated into the nucleus, colocalized with DNA and induced cell
      death. A mannose-binding motif and a V(103)-W(130) region directed the nuclear
      translocation of PPA. Coprecipitation, mass spectrometry and western blotting
      analysis further indentified that PPA was associated with the methylosome, which
      contains methylosome protein 50 and protein arginine methyltransferase 5 (PRMT5).
      Knockdown of PRMT5 significantly inhibited the PPA-induced cell death, suggesting
      that PPA used the methylosome as a target. Furthermore, Ad.surp-PPA, an
      adenovirus vector in which the PPA gene was controlled by a survivin promoter
      (surp), selectively inhibited the proliferation of cancer cell lines. Taken
      together, the expression of PPA gene elicited significant cytotoxicity to cancer
      cells through targeting the methylosome and might be developed into a novel agent
      in cancer gene therapy.

PMID- 23552402
TI  - DNA replication stress response involving PLK1, CDC6, POLQ, RAD51 and CLASPIN
      upregulation prognoses the outcome of early/mid-stage non-small cell lung cancer
      patients.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. Clinical staging
      classification is generally insufficient to provide a reliable prognosis,
      particularly for early stages. In addition, prognostic factors are therefore
      needed to better forecast life expectancy and optimize adjuvant therapeutic
      strategy. Recent evidence indicates that alterations of the DNA replication
      program contribute to neoplasia from its early stages and that cancer cells are
      frequently exposed to endogenous replication stress. We therefore hypothesized
      that genes involved in the replication stress response may represent an under
      explored source of biomarkers. Expressions of 77 DNA replication-associated genes
      implicated in different aspects of chromosomal DNA replication, including
      licensing, firing of origins, elongation, replication fork maintenance and
      recovery, lesion bypass and post-replicative repair were determined in primary
      tumors and adjacent normal tissues from 93 patients suffering from early- or mid
      stage non-small cell lung cancer (NSCLC). We then investigated a statistically
      significant interaction between gene expressions and survival of early-stage
      NSCLC patients.The expression of five genes, that is, POLQ, PLK1, RAD51, CLASPIN
      and CDC6 was associated with overall, disease-free and relapse-free survival. The
      expression levels are independent of treatment and stage classification. Except
      RAD51, their prognostic role on survival persists after adjustment on age, sex,
      treatment, stage classification and conventional proliferation markers, with a
      hazard ratio of 36.3 for POLQ (95%CI 2.6-517.4, P=0.008), 23.5 for PLK1 (95%CI
      1.9-288.4, P=0.01), 20.7 for CLASPIN (95%CI 1.5-275.9, P=0.02) and 18.5 for CDC6
      (95%CI 1.3-267.4, P=0.03). We also show that a five-gene signature including
      POLQ, PLK1, RAD51, CLASPIN and CDC6 separates patients into low- and high-risk
      groups, with a hazard ratio of 14.3 (95% CI 5.1-40.3, P<0.001). This 'replication
      stress' metamarker may be a reliable predictor of survival for NSCLC, and may
      also help understand the molecular mechanisms underlying tumor progression.

PMID- 23552404
TI  - Primary mastoid cyst.
AB  - OBJECTIVE: To report an unusual case of a primary mastoid cyst (congenital or
      developmental) in a patient without otological symptoms. METHOD: Case report and
      review of the English language literature. RESULTS: Primary mastoid cyst is a
      newly reported and very rare pathological entity. Mastoid cysts usually occur
      secondary to chronic infection, inflammation or trauma. Review of the medical
      literature highlights the rarity of this condition. CONCLUSION: This report
      describes the experience gained by the diagnosis and management of this patient.
      It emphasises the importance of clinical vigilance so that proper treatment may
      be instituted in a timely manner.

PMID- 23552403
TI  - Functional consequences of WNT3/Frizzled7-mediated signaling in non-transformed
      hepatic cells.
AB  - We have previously demonstrated that WNT3 and Frizzled7 (FZD7) expression
      levelswere upregulated in hepatocellular carcinoma (HCC) and that they directly
      interact to activate the canonical Wnt/beta-catenin pathway in HCC cell lines. In
      this study, we investigated the functional consequences of WNT3 and FZD7
      expression levels in non-transformed hepatic cells to address the question of
      whether WNT3/FZD7-mediated signal transduction could be involved in cellular
      transformation. After stable transfection of WNT3 and FZD7, the activation of the
      Wnt/beta-catenin pathway was confirmed by western blot, immunostaining and
      quantitative real-time reverse transcriptase-PCR (qRT-PCR) analysis in two non
      transformed hepatocyte-derived cell lines. In vitro characteristics of the
      malignant phenotype were measured, including cell proliferation, migration,
      invasion and anchorage-independent growth in soft agar. Stable expression of WNT3
      and FZD7 in the two cell lines led to cellular accumulation of beta-catenin and
      expression of downstream target genes activated by this pathway. In the stable
      WNT3/FZD7-expressing clones, hepatic cell proliferation, migration, invasion as
      well as soft agar colony formation were enhanced compared with the non
      transformed control cells. The epithelial-mesenchymal transition (EMT) factors,
      Twist, Snail and Vimentin, were increased in cells expressing WNT3 and FZD7.
      However, the WNT3/FZD7-expressing cells did not form tumors in vivo. We conclude
      that activation of the WNT3/FZD7 canonical pathway has a role in the early stages
      of hepatocarcinogenesis by promoting the acquisition of a malignant phenotype
      with features of EMT.

PMID- 23552405
TI  - The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a
      narrative review.
AB  - It has been 20 years since the first description of a rapidly progressive renal
      disease that is associated with the consumption of Chinese herbs containing
      aristolochic acid (AA) and is now termed aristolochic acid nephropathy (AAN).
      Recent data have shown that AA is also the primary causative agent in Balkan
      endemic nephropathy and associated urothelial cancer. Aristolochic acid
      nephropathy is associated with a high long-term risk for renal failure and
      urothelial cancer, and the potential worldwide population exposure is enormous.
      This evidence-based review of the diagnostic approach to and management of AAN
      draws on the authors' experience with the largest and longest-studied combined
      cohort of patients with this condition. It is hoped that a better understanding
      of the importance of this underrecognized and severe condition will improve
      epidemiologic, preventive, and therapeutic strategies to reduce the global burden
      of this disease.

PMID- 23552406
TI  - Photophysical properties of NIR-emitting fluorescence probes: insights from TD
      DFT.
AB  - The complex electronic structure and spectroscopic properties of a class of six
      molecules behaving as near infrared (NIR) fluorescence probes, recently
      experimentally characterized, are investigated and rationalized using a
      computational protocol based on Density Functional Theory (DFT) and Time
      Dependent DFT (TD-DFT). These systems, all belonging to the seminaphthofluorone
      (SNAFR) series, are characterized by a controlled direction of annulation and
      regiochemistry of the ionizable moieties significantly tuning the overall
      absorption and emission features. Experimentally, the overall spectroscopic
      properties depend both on the pH and on the possible coexistence of different
      tautomers and regioisomers in solution, thus making the quantitative prediction
      of their absorption and emission features a challenging task for current ab
      initio approaches, due to the need for an accurate description of both ground and
      excited state potential energy landscapes. The results obtained in the present
      study illustrate the possibility of using a unique computational protocol to
      describe complex molecular systems in solution not only for the analysis of their
      intermingled spectroscopic properties but, more interestingly, for the design of
      new compounds for technological (white emitting dyes) and biological (ratiometric
      probes) applications.

PMID- 23552407
TI  - Genome-wide analysis of host mRNA translation during hepatitis C virus infection.
AB  - In the model of Huh-7.5.1 hepatocyte cells infected by the JFH1 hepatitis C virus
      (HCV) strain, transcriptomic and proteomic studies have revealed modulations of
      pathways governing mainly apoptosis and cell cycling. Differences between
      transcriptomic and proteomic studies pointed to regulations occurring at the
      posttranscriptional level, including the control of mRNA translation. In this
      study, we investigated at the genome-wide level the translational regulation
      occurring during HCV infection. Sucrose gradient ultracentrifugation followed by
      microarray analysis was used to identify translationally regulated mRNAs (mRNAs
      associated with ribosomes) from JFH1-infected and uninfected Huh-7.5.1 cells.
      Translationally regulated mRNAs were found to correspond to genes enriched in
      specific pathways, including vesicular transport and posttranscriptional
      regulation. Interestingly, the strongest translational regulation was found for
      mRNAs encoding proteins involved in pre-mRNA splicing, mRNA translation, and
      protein folding. Strikingly, these pathways were not previously identified,
      through transcriptomic studies, as being modulated following HCV infection.
      Importantly, the observed changes in host mRNA translation were directly due to
      HCV replication rather than to HCV entry, since they were not observed in JFH1
      infected Huh-7.5.1 cells treated with a potent HCV NS3 protease inhibitor.
      Overall, this study highlights the need to consider, beyond transcriptomic or
      proteomic studies, the modulation of host mRNA translation as an important aspect
      of HCV infection.

PMID- 23552408
TI  - Three-dimensional architecture of tick-borne encephalitis virus replication sites
      and trafficking of the replicated RNA.
AB  - Flavivirus replication is accompanied by the rearrangement of cellular membranes
      that may facilitate viral genome replication and protect viral components from
      host cell responses. The topological organization of viral replication sites and
      the fate of replicated viral RNA are not fully understood. We exploited electron
      microscopy to map the organization of tick-borne encephalitis virus (TBEV)
      replication compartments in infected cells and in cells transfected with a
      replicon. Under both conditions, 80-nm vesicles were seen within the lumen of the
      endoplasmic reticulum (ER) that in infected cells also contained virions. By
      electron tomography, the vesicles appeared as invaginations of the ER membrane,
      displaying a pore that could enable release of newly synthesized viral RNA into
      the cytoplasm. To track the fate of TBEV RNA, we took advantage of our recently
      developed method of viral RNA fluorescent tagging for live-cell imaging combined
      with bleaching techniques. TBEV RNA was found outside virus-induced vesicles
      either associated to ER membranes or free to move within a defined area of
      juxtaposed ER cisternae. From our results, we propose a biologically relevant
      model of the possible topological organization of flavivirus replication
      compartments composed of replication vesicles and a confined extravesicular space
      where replicated viral RNA is retained. Hence, TBEV modifies the ER membrane
      architecture to provide a protected environment for viral replication and for the
      maintenance of newly replicated RNA available for subsequent steps of the virus
      life cycle.

PMID- 23552409
TI  - Nuclear transport of Epstein-Barr virus DNA polymerase is dependent on the BMRF1
      polymerase processivity factor and molecular chaperone Hsp90.
AB  - Epstein-Barr virus (EBV) replication proteins are transported into the nucleus to
      synthesize viral genomes. We here report molecular mechanisms for nuclear
      transport of EBV DNA polymerase. The EBV DNA polymerase catalytic subunit BALF5
      was found to accumulate in the cytoplasm when expressed alone, while the EBV DNA
      polymerase processivity factor BMRF1 moved into the nucleus by itself.
      Coexpression of both proteins, however, resulted in efficient nuclear transport
      of BALF5. Deletion of the nuclear localization signal of BMRF1 diminished the
      proteins' nuclear transport, although both proteins can still interact. These
      results suggest that BALF5 interacts with BMRF1 to effect transport into the
      nucleus. Interestingly, we found that Hsp90 inhibitors or knockdown of Hsp90beta
      with short hairpin RNA prevented the BALF5 nuclear transport, even in the
      presence of BMRF1, both in transfection assays and in the context of lytic
      replication. Immunoprecipitation analyses suggested that the molecular chaperone
      Hsp90 interacts with BALF5. Treatment with Hsp90 inhibitors blocked viral DNA
      replication almost completely during lytic infection, and knockdown of Hsp90beta
      reduced viral genome synthesis. Collectively, we speculate that Hsp90 interacts
      with BALF5 in the cytoplasm to assist complex formation with BMRF1, leading to
      nuclear transport. Hsp90 inhibitors may be useful for therapy for EBV-associated
      diseases in the future.

PMID- 23552410
TI  - Toscana virus NSs protein inhibits the induction of type I interferon by
      interacting with RIG-I.
AB  - Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is
      responsible for central nervous system (CNS) injury in humans. Previous data have
      shown that the TOSV NSs protein is a gamma interferon (IFN-beta) antagonist when
      transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori
      Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J.
      Gen. Virol. 92:71-79, 2011). In this study, we investigated whether an upstream
      sensor, which has a role in the signaling cascade leading to the production of
      type I IFN, was involved. We found a significant decrease in RIG-I protein levels
      in cells overexpressing TOSV NSs, suggesting that the nonstructural protein
      interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG
      132 proteasome inhibitor was able to restore IFN-beta promoter activation in
      cells expressing NSs, demonstrating the existence of an evasion mechanism based
      on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs
      protein (DeltaNSs), although able to interact with RIG-I, did not affect the RIG
      I-mediated IFN-beta promoter activation, suggesting that the NSs domains
      responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on
      different regions. These results contribute to identify a novel mechanism for
      bunyaviruses by which TOSV NSs counteracts the early IFN response.

PMID- 23552411
TI  - Identification of virulence determinants within the L genomic segment of the
      pichinde arenavirus.
AB  - Several arenaviruses are responsible for causing viral hemorrhagic fevers (VHF)
      in humans. Lassa virus (LASV), the causative agent of Lassa fever, is a biosafety
      level 4 (BSL4) pathogen that requires handling in BSL4 facilities. In contrast,
      the Pichinde arenavirus (PICV) is a BSL2 pathogen that can cause hemorrhagic
      fever-like symptoms in guinea pigs that resemble those observed in human Lassa
      fever. Comparative sequence analysis of the avirulent P2 strain of PICV and the
      virulent P18 strain shows a high degree of sequence homology in the bisegmented
      genome between the two strains despite the polarized clinical outcomes noted for
      the infected animals. Using reverse genetics systems that we have recently
      developed, we have mapped the sequence changes in the large (L) segment of the
      PICV genome that are responsible for the heightened virulence phenotype of the
      P18 strain. By monitoring the degree of disease severity and lethality caused by
      the different mutant viruses, we have identified specific residues located within
      the viral L polymerase gene encoded on the L segment essential for mediating
      disease pathogenesis. Through quantitative reverse transcription-PCR (RT-PCR)
      analysis, we have confirmed that the same set of residues is responsible for the
      increased viral replicative potential of the P18 strain and its heightened
      disease severity in vivo. Our laboratory findings serve to reinforce field
      observations that a high level of viremia often correlates with severe disease
      outcomes in LASV-infected patients.

PMID- 23552412
TI  - A variant macaque-tropic human immunodeficiency virus type 1 is resistant to
      alpha interferon-induced restriction in pig-tailed macaque CD4+ T cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) antagonizes innate restriction
      factors in order to infect and persistently replicate in a host. In a previous
      study, we demonstrated that HIV-1 NL4-3 with a simian immunodeficiency virus mne
      (SIVmne) vif gene substitution (HSIV-vif-NL4-3) could infect and replicate in pig
      tailed macaques (PTM), indicating that APOBEC3 proteins are primary barriers to
      transmission. Because viral replication was persistent but low, we hypothesized
      that HSIV-vif-NL4-3 may be suppressed by type I interferons (IFN-I), which are
      known to upregulate the expression of innate restriction factors. Here, we
      demonstrate that IFN-alpha more potently suppresses HSIV-vif-NL4-3 in PTM CD4(+)
      T cells than it does pathogenic SIVmne027. Importantly, we identify a variant
      (HSIV-vif-Yu2) that is resistant to IFN-alpha, indicating that the IFN-alpha
      induced barrier can be overcome by HSIV-vif chimeras in PTM CD4(+) T cells.
      Interestingly, HSIV-vif-Yu2 and HSIV-vif-NL4-3 are similarly restricted by PTM
      BST2/Tetherin, and neither virus downregulates it from the surface of infected
      PTM CD4(+) T cells. Resistance to IFN-alpha-induced restriction appears to be
      conferred by a determinant in HSIV-vif-Yu2 that includes env su. Finally, we show
      that the Yu-2 env su allele may overcome an IFN-alpha-induced barrier to entry.
      Together, our data demonstrate that the prototype macaque-tropic HIV-1 clones
      based on NL4-3 may not sufficiently antagonize innate restriction in PTM cells.
      However, variants with resistance to IFN-alpha-induced restriction factors in PTM
      CD4(+) T cells may enhance viral replication by overcoming a barrier early in the
      viral replication cycle.

PMID- 23552413
TI  - Structure of a classical broadly neutralizing stem antibody in complex with a
      pandemic H2 influenza virus hemagglutinin.
AB  - We report the structural characterization of the first antibody identified to
      cross-neutralize multiple subtypes of influenza A viruses. The crystal structure
      of mouse antibody C179 bound to the pandemic 1957 H2N2 hemagglutinin (HA) reveals
      that it targets an epitope on the HA stem similar to those targeted by the
      recently identified human broadly neutralizing antibodies. C179 also inhibits the
      low-pH conformational change of the HA but uses a different angle of approach and
      both heavy and light chains.

PMID- 23552414
TI  - Vesicular stomatitis virus variants selectively infect and kill human melanomas
      but not normal melanocytes.
AB  - Metastatic malignant melanoma remains one of the most therapeutically challenging
      forms of cancer. Here we test replication-competent vesicular stomatitis viruses
      (VSV) on 19 primary human melanoma samples and compare these infections with
      those of normal human melanocyte control cells. Even at a low viral
      concentration, we found a strong susceptibility to viral oncolysis in over 70% of
      melanomas. In contrast, melanocytes displayed strong resistance to virus
      infection and showed complete protection by interferon. Several recombinant VSVs
      were compared, and all infected and killed most melanomas with differences in the
      time course with increasing rates of melanoma infection, as follows: VSV-CT9-M51
      < VSV-M51 < VSV-G/GFP < VSV-rp30. VSV-rp30 sequencing revealed 2 nonsynonymous
      mutations at codon positions P126 and L223, both of which appear to be required
      for the enhanced phenotype. VSV-rp30 showed effective targeting and infection of
      multiple subcutaneous and intracranial melanoma xenografts in SCID mice after
      tail vein virus application. Sequence analysis of mutations in the melanomas used
      revealed that BRAF but not NRAS gene mutation status was predictive for enhanced
      susceptibility to infection. In mouse melanoma models with specific induced gene
      mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral
      infection correlated with the extent of malignant transformation. Similar to
      human melanocytes, mouse melanocytes resisted VSV-rp30 infection. This study
      confirms the general susceptibility of the majority of human melanoma types for
      VSV-mediated oncolysis.

PMID- 23552415
TI  - Different distributions of Epstein-Barr virus early and late gene transcripts
      within viral replication compartments.
AB  - Productive replication of the Epstein-Barr virus (EBV) occurs in discrete sites
      in nuclei, called replication compartments, where viral genome DNA synthesis and
      transcription take place. The replication compartments include subnuclear
      domains, designated BMRF1 cores, which are highly enriched in the BMRF1 protein.
      During viral lytic replication, newly synthesized viral DNA genomes are organized
      around and then stored inside BMRF1 cores. Here, we examined spatial distribution
      of viral early and late gene mRNAs within replication compartments using confocal
      laser scanning microscopy and three-dimensional surface reconstruction imaging.
      EBV early mRNAs were mainly located outside the BMRF1 cores, while viral late
      mRNAs were identified inside, corresponding well with the fact that late gene
      transcription is dependent on viral DNA replication. From these results, we
      speculate that sites for viral early and late gene transcription are separated
      with reference to BMRF1 cores.

PMID- 23552416
TI  - Novel recombinant hepatitis B virus vectors efficiently deliver protein and RNA
      encoding genes into primary hepatocytes.
AB  - Hepatitis B virus (HBV) has extremely restricted host and hepatocyte tropism. HBV
      based vectors could form the basis of novel therapies for chronic hepatitis B and
      other liver diseases and would also be invaluable for the study of HBV infection.
      Previous attempts at developing HBV-based vectors encountered low yields of
      recombinant viruses and/or lack of sufficient infectivity/cargo gene expression
      in primary hepatocytes, which hampered follow-up applications. In this work, we
      constructed a novel vector based on a naturally occurring, highly replicative HBV
      mutant with a 207-bp deletion in the preS1/polymerase spacer region. By applying
      a novel insertion strategy that preserves the continuity of the polymerase open
      reading frame (ORF), recombinant HBV (rHBV) carrying protein or small interfering
      RNA (siRNA) genes were obtained that replicated and were packaged efficiently in
      cultured hepatocytes. We demonstrated that rHBV expressing a fluorescent reporter
      (DsRed) is highly infective in primary tree shrew hepatocytes, and rHBV
      expressing HBV-targeting siRNA successfully inhibited antigen expression from
      coinfected wild-type HBV. This novel HBV vector will be a powerful tool for
      hepatocyte-targeting gene delivery, as well as the study of HBV infection.

PMID- 23552417
TI  - Human La protein interaction with GCAC near the initiator AUG enhances hepatitis
      C Virus RNA replication by promoting linkage between 5' and 3' untranslated
      regions.
AB  - Human La protein has been implicated in facilitating the internal initiation of
      translation as well as replication of hepatitis C virus (HCV) RNA. Previously, we
      demonstrated that La interacts with the HCV internal ribosome entry site (IRES)
      around the GCAC motif near the initiator AUG within stem-loop IV by its RNA
      recognition motif (RRM) (residues 112 to 184) and influences HCV translation. In
      this study, we have deciphered the role of this interaction in HCV replication in
      a hepatocellular carcinoma cell culture system. We incorporated mutation of the
      GCAC motif in an HCV monocistronic subgenomic replicon and a pJFH1 construct
      which altered the binding of La and checked HCV RNA replication by reverse
      transcriptase PCR (RT-PCR). The mutation drastically affected HCV replication.
      Furthermore, to address whether the decrease in replication is a consequence of
      translation inhibition or not, we incorporated the same mutation into a
      bicistronic replicon and observed a substantial decrease in HCV RNA levels.
      Interestingly, La overexpression rescued this inhibition of replication. More
      importantly, we observed that the mutation reduced the association between La and
      NS5B. The effect of the GCAC mutation on the translation-to-replication switch,
      which is regulated by the interplay between NS3 and La, was further investigated.
      Additionally, our analyses of point mutations in the GCAC motif revealed distinct
      roles of each nucleotide in HCV replication and translation. Finally, we showed
      that a specific interaction of the GCAC motif with human La protein is crucial
      for linking 5' and 3' ends of the HCV genome. Taken together, our results
      demonstrate the mechanism of regulation of HCV replication by interaction of the
      cis-acting element GCAC within the HCV IRES with human La protein.

PMID- 23552418
TI  - HIV-1 Vpu does not degrade interferon regulatory factor 3.
AB  - It has been reported that HIV-1 Vpu mediates the degradation of interferon
      regulatory factor 3 (IRF-3) to avoid innate immune sensing. Here, we show that
      Vpu does not deplete IRF-3 from transfected cell lines or HIV-1-infected primary
      cells. Furthermore, the Vpu-dependent suppression of beta interferon expression
      described in previous studies could be ascribed to inhibition of NF-kappaB
      activation. Thus, Vpu suppresses innate immune activation through inhibition of
      NF-kappaB rather than degradation of IRF-3.

PMID- 23552419
TI  - Vaxfectin adjuvant improves antibody responses of juvenile rhesus macaques to a
      DNA vaccine encoding the measles virus hemagglutinin and fusion proteins.
AB  - DNA vaccines formulated with the cationic lipid-based adjuvant Vaxfectin induce
      protective immunity in macaques after intradermal (i.d.) or intramuscular (i.m.)
      delivery of 0.5 to 1 mg of codon-optimized DNA encoding the hemagglutinin (H) and
      fusion (F) proteins of measles virus (MeV). To characterize the effect of
      Vaxfectin at lower doses of H+F DNA, rhesus macaques were vaccinated twice with
      20 MUg of DNA plus Vaxfectin i.d., 100 MUg of DNA plus Vaxfectin i.d., 100 MUg of
      DNA plus Vaxfectin i.m. or 100 MUg of DNA plus phosphate-buffered saline (PBS)
      i.m. using a needleless Biojector device. The levels of neutralizing (P = 0.036)
      and binding (P = 0.0001) antibodies were higher after 20 or 100 MUg of DNA plus
      Vaxfectin than after 100 MUg of DNA plus PBS. Gamma interferon (IFN-gamma)
      producing T cells were induced more rapidly than antibody, but were not improved
      with Vaxfectin. At 18 months after vaccination, monkeys were challenged with wild
      type MeV. None developed rash or viremia, but all showed evidence of infection.
      Antibody levels increased, and IFN-gamma- and interleukin-17-producing T cells,
      including cells specific for the nucleoprotein absent from the vaccine, were
      induced. At 3 months after challenge, MeV RNA was detected in the leukocytes of
      two monkeys. The levels of antibody peaked 2 to 4 weeks after challenge and then
      declined in vaccinated animals reflecting low numbers of bone marrow-resident
      plasma cells. Therefore, Vaxfectin was dose sparing and substantially improved
      the antibody response to the H+F DNA vaccine. This immune response led to
      protection from disease (rash/viremia) but not from infection. Antibody responses
      after challenge were more transient in vaccinated animals than in an unvaccinated
      animal.

PMID- 23552420
TI  - In memoriam Kuan-Teh Jeang (1958-2013): retrovirologist par excellence and
      founding editor of Retrovirology.

PMID- 23552421
TI  - Complete genome sequences of elephant endotheliotropic herpesviruses 1A and 1B
      determined directly from fatal cases.
AB  - A highly lethal hemorrhagic disease associated with infection by elephant
      endotheliotropic herpesvirus (EEHV) poses a severe threat to Asian elephant
      husbandry. We have used high-throughput methods to sequence the genomes of the
      two genotypes that are involved in most fatalities, namely, EEHV1A and EEHV1B
      (species Elephantid herpesvirus 1, genus Proboscivirus, subfamily
      Betaherpesvirinae, family Herpesviridae). The sequences were determined from
      postmortem tissue samples, despite the data containing tiny proportions of viral
      reads among reads from a host for which the genome sequence was not available.
      The EEHV1A genome is 180,421 bp in size and consists of a unique sequence
      (174,601 bp) flanked by a terminal direct repeat (2,910 bp). The genome contains
      116 predicted protein-coding genes, of which six are fragmented, and seven
      paralogous gene families are present. The EEHV1B genome is very similar to that
      of EEHV1A in structure, size, and gene layout. Half of the EEHV1A genes lack
      orthologs in other members of subfamily Betaherpesvirinae, such as human
      cytomegalovirus (genus Cytomegalovirus) and human herpesvirus 6A (genus
      Roseolovirus). Notable among these are 23 genes encoding type 3 membrane proteins
      containing seven transmembrane domains (the 7TM family) and seven genes encoding
      related type 2 membrane proteins (the EE50 family). The EE50 family appears to be
      under intense evolutionary selection, as it is highly diverged between the two
      genotypes, exhibits evidence of sequence duplications or deletions, and contains
      several fragmented genes. The availability of the genome sequences will
      facilitate future research on the epidemiology, pathogenesis, diagnosis, and
      treatment of EEHV-associated disease.

PMID- 23552422
TI  - Tropism of and innate immune responses to the novel human betacoronavirus lineage
      C virus in human ex vivo respiratory organ cultures.
AB  - Since April 2012, there have been 17 laboratory-confirmed human cases of
      respiratory disease associated with newly recognized human betacoronavirus
      lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility
      and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its
      cellular tropism in human respiratory tissues will provide mechanistic insights
      into the key cellular targets for virus propagation and spread. We utilized ex
      vivo cultures of human bronchial and lung tissue specimens to investigate the
      tissue tropism and virus replication kinetics following experimental infection
      with HCoV-EMC compared with those following infection with human coronavirus 229E
      (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The
      innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC
      productively replicated in human bronchial and lung ex vivo organ cultures. While
      SARS-CoV productively replicated in lung tissue, replication in human bronchial
      tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected
      nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar
      epithelial cells, and endothelial cells. Transmission electron microscopy showed
      virions within the cytoplasm of bronchial epithelial cells and budding virions
      from alveolar epithelial cells (type II). In contrast, there was minimal HCoV
      229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III
      interferon (IFN) or proinflammatory innate immune responses in ex vivo
      respiratory tissue cultures. Treatment of human lung tissue ex vivo organ
      cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the
      replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for
      treatment of human infection.

PMID- 23552423
TI  - EWSR1 binds the hepatitis C virus cis-acting replication element and is required
      for efficient viral replication.
AB  - The hepatitis C virus (HCV) genome contains numerous RNA elements that are
      required for its replication. Most of the identified RNA structures are located
      within the 5' and 3' untranslated regions (UTRs). One prominent RNA structure,
      termed the cis-acting replication element (CRE), is located within the NS5B
      coding region. Mutation of part of the CRE, the 5BSL3.2 stem-loop, impairs HCV
      RNA replication. This loop has been implicated in a kissing interaction with a
      complementary stem-loop structure in the 3' UTR. Although it is clear that this
      interaction is required for viral replication, the function of the interaction,
      and its regulation are unknown. In order to gain insight into the CRE function,
      we isolated cellular proteins that preferentially bind the CRE and identified
      them using mass spectrometry. This approach identified EWSR1 as a CRE-binding
      protein. Silencing EWSR1 expression impairs HCV replication and infectious virus
      production but not translation. While EWRS1 is a shuttling protein that is
      extensively nuclear in hepatocytes, substantial amounts of EWSR1 localize to the
      cytosol in HCV-infected cells and colocalize with sites of HCV replication. A
      subset of EWRS1 translocates into detergent-resistant membrane fractions, which
      contain the viral replicase proteins, in cells with replicating HCV. EWSR1
      directly binds the CRE, and this is dependent on the intact CRE structure.
      Finally, EWSR1 preferentially interacts with the CRE in the absence of the
      kissing interaction. This study implicates EWSR1 as a novel modulator of CRE
      function in HCV replication.

PMID- 23552424
TI  - Evidence in support of RNA-mediated inhibition of phosphatidylserine-dependent
      HIV-1 Gag membrane binding in cells.
AB  - The matrix domain promotes plasma-membrane-specific binding of HIV-1 Gag through
      interaction with an acidic lipid phosphatidylinositol-(4,5)-bisphosphate. In in
      vitro systems, matrix-bound RNA suppresses Gag interactions with
      phosphatidylserine, an acidic lipid prevalent in various cytoplasmic membranes,
      thereby enhancing the lipid specificity of the matrix domain. Here we provide in
      vitro and cell-based evidence supporting the idea that this RNA-mediated
      suppression occurs in cells and hence is a physiologically relevant mechanism
      that prevents Gag from binding promiscuously to phosphatidylserine-containing
      membranes.

PMID- 23552425
TI  - The adenovirus L4-33K protein regulates both late gene expression patterns and
      viral DNA packaging.
AB  - The adenovirus (Ad) L4-33K protein has been linked to disparate functions during
      infection. L4-33K is a virus-encoded alternative RNA splicing factor which
      activates splicing of viral late gene transcripts that contain weak 3' splice
      sites. Additionally, L4-33K has been indicated to play a role in adenovirus
      assembly. We generated and characterized an Ad5 L4-33K mutant virus to further
      explore its function(s) during infection. Infectivity, viral genome replication,
      and most viral gene expression of the L4-33K mutant virus are comparable to those
      of the wild-type virus, except for a prominent decrease in the levels of the late
      proteins IIIa and pVI. The L4-33K mutant virus produces only empty capsids,
      indicating a defect in viral DNA packaging. We demonstrate that L4-33K does not
      preferentially bind to viral packaging sequences in vivo, and mutation of L4-33K
      does not interfere with the binding of the known viral packaging proteins IVa2,
      L4-22K, L1-52/55K, and IIIa to the packaging sequences in vivo. Collectively,
      these results demonstrate that the phenotype of an Ad5 L4-33K mutant virus is
      complex. The L4-33K protein regulates the accumulation of selective Ad late gene
      mRNAs and is involved in the proper transition of gene expression during the late
      phase of infection. The L4-33K protein also plays a role in adenovirus
      morphogenesis by promoting the packaging of the viral genome into the empty
      capsid. These results demonstrate the multifunctional nature of the L4-33K
      protein and its involvement in several different and critical aspects of viral
      infection.

PMID- 23552426
TI  - Ets-1 is required for the activation of VEGFR3 during latent Kaposi's sarcoma
      associated herpesvirus infection of endothelial cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's
      sarcoma (KS), is present in the predominant tumor cells of KS, the spindle cells.
      Spindle cells express markers of lymphatic endothelium and, interestingly, KSHV
      infection of blood endothelial cells reprograms them to a lymphatic endothelial
      cell phenotype. KSHV-induced reprogramming requires the activation of STAT3 and
      phosphatidylinositol 3 (PI3)/AKT through the activation of cellular receptor
      gp130. Importantly, KSHV-induced reprogramming is specific to endothelial cells,
      indicating that there are additional host genes that are differentially regulated
      during KSHV infection of endothelial cells that contribute to lymphatic
      reprogramming. We found that the transcription factor Ets-1 is highly expressed
      in KS spindle cells and is upregulated during KSHV infection of endothelial cells
      in culture. The KSHV latent vFLIP gene is sufficient to induce Ets-1 expression
      in an NF-kappaB-dependent fashion. Ets-1 is required for KSHV-induced expression
      of VEGFR3, a lymphatic endothelial-cell-specific receptor important for
      lymphangiogenesis, and Ets-1 activates the promoter of VEGFR3. Ets-1 knockdown
      does not alter the expression of another lymphatic-specific gene, the podoplanin
      gene, but does inhibit the expression of VEGFR3 in uninfected lymphatic
      endothelium, indicating that Ets-1 is a novel cellular regulator of VEGFR3
      expression. Knockdown of Ets-1 affects the ability of KSHV-infected cells to
      display angiogenic phenotypes, indicating that Ets-1 plays a role in KSHV
      activation of endothelial cells during latent KSHV infection. Thus, Ets-1 is a
      novel regulator of VEGFR3 and is involved in the induction of angiogenic
      phenotypes by KSHV.

PMID- 23552427
TI  - Chikungunya virus host range E2 transmembrane deletion mutants induce protective
      immunity against challenge in C57BL/6J mice.
AB  - A vaccine against Chikungunya virus (ChikV), a reemerging pathogenic arbovirus,
      has been made by attenuating wild-type (WT) virus via truncation of the
      transmembrane domain (TMD) of E2 and selecting for host range (HR) mutants. Mice
      are a standard model system for ChikV disease and display the same symptoms of
      the disease seen in humans. Groups of mice were inoculated with one of three
      ChikV HR mutants to determine the ability of each mutant strain to elicit
      neutralizing antibody and protective immunity upon virus challenge. One mutant,
      ChikV TM17-2, fulfilled the criteria for a good vaccine candidate. It displayed
      no reactogenicity at the site of injection, no tissue disease in the foot/ankle
      and quadriceps, and no evidence of viral persistence in foot/ankle tissues 21
      days after infection. Upon challenge with a highly pathogenic strain of ChikV,
      the mutant blocked viral replication in all tissues tested. This study identified
      a ChikV HR mutant that grows to high levels in insect cells but was restricted in
      the ability to assemble virus in mammalian cells in vitro. The study demonstrates
      that these HR strains are attenuated in the mammalian host and warrant further
      development as live-attenuated vaccine strains.

PMID- 23552428
TI  - A novel victorivirus from a phytopathogenic fungus, Rosellinia necatrix, is
      infectious as particles and targeted by RNA silencing.
AB  - A novel victorivirus, termed Rosellinia necatrix victorivirus 1 (RnVV1), was
      isolated from a plant pathogenic ascomycete, white root rot fungus Rosellinia
      necatrix, coinfected with a partitivirus. The virus was molecularly and
      biologically characterized using the natural and experimental hosts (chestnut
      blight fungus, Cryphonectria parasitica). RnVV1 was shown to have typical
      molecular victorivirus attributes, including a monopartite double-stranded RNA
      genome with two open reading frames (ORFs) encoding capsid protein (CP) and RNA
      dependent RNA polymerase (RdRp), a UAAUG pentamer presumed to facilitate the
      coupled termination/reinitiation for translation of the two ORFs, a spherical
      particle structure ~40 nm in diameter, and moderate levels of CP and RdRp
      sequence identity (34 to 58%) to those of members of the genus Victorivirus
      within the family Totiviridae. A reproducible transfection system with purified
      RnVV1 virions was developed for the two distinct fungal hosts. Transfection assay
      with purified RnVV1 virions combined with virus elimination by hyphal tipping
      showed that the effects of RnVV1 on the phenotype of the natural host were
      negligible. Interestingly, comparison of the RNA silencing-competent (standard
      strain EP155) and -defective (Deltadcl-2) strains of C. parasitica infected with
      RnVV1 showed that RNA silencing acted against the virus to repress its
      replication, which was restored by coinfection with hypovirus or transgenic
      expression of an RNA silencing suppressor, hypovirus p29. Phenotypic changes were
      observed in the Deltadcl-2 strain but not in EP155. This is the first reported
      study on the host range expansion of a Totiviridae member that is targeted by RNA
      silencing.

PMID- 23552429
TI  - Do race, ethnicity, and psychiatric diagnoses matter in the prevalence of
      multiple chronic medical conditions?
AB  - BACKGROUND: The proportion of people in the United States with multiple chronic
      medical conditions (MCMC) is increasing. Yet, little is known about the
      relationship that race, ethnicity, and psychiatric disorders have on the
      prevalence of MCMCs in the general population. METHODS: This study used data from
      wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions
      (N=33,107). Multinomial logistic regression models adjusting for sociodemographic
      variables, body mass index, and quality of life were used to examine differences
      in the 12-month prevalence of MCMC by race/ethnicity, psychiatric diagnosis, and
      the interactions between race/ethnicity and psychiatric diagnosis. RESULTS:
      Compared to non-Hispanic Whites, Hispanics reported lower odds of MCMC and
      African Americans reported higher odds of MCMC after adjusting for covariates.
      People with psychiatric disorders reported higher odds of MCMC compared with
      people without psychiatric disorders. There were significant interactions between
      race and psychiatric diagnosis associated with rates of MCMC. In the presence of
      certain psychiatric disorders, the odds of MCMC were higher among African
      Americans with psychiatric disorders compared to non-Hispanic Whites with similar
      psychiatric disorders. CONCLUSIONS: Our study results indicate that race,
      ethnicity, and psychiatric disorders are associated with the prevalence of MCMC.
      As the rates of MCMC rise, it is critical to identify which populations are at
      increased risk and how to best direct services to address their health care
      needs.

PMID- 23552430
TI  - Overuse and systems of care: a systematic review.
AB  - BACKGROUND: Current health care reform efforts are focused on reorganizing health
      care systems to reduce waste in the US health care system. OBJECTIVE: To compare
      rates of overuse in different health care systems and examine whether certain
      systems of care or insurers have lower rates of overuse of health care services.
      DATA SOURCES: Articles published in MEDLINE between 1978, the year of publication
      of the first framework to measure quality, and June 21, 2012. STUDY SELECTION:
      Included studies compared rates of overuse of procedures, diagnostic tests, or
      medications in at least 2 systems of care. DATA EXTRACTION: Four reviewers
      screened titles; 2 reviewers screened abstracts and full articles and extracted
      data. RESULTS: We identified 7 studies which compared rates of overuse of 5
      services across multiple different health care settings. National rates of
      inappropriate coronary angiography were similar in Medicare HMOs and Medicare FFS
      (13% vs. 13%, P=0.33) and in a state-based study comparing 15 hospitals in New
      York and 4 hospitals in a Massachusetts-managed care plan (4% vs. 6%, P>0.1).
      Rates of carotid endarterectomy in New York State were similar in Medicare HMOs
      and Medicare FFS plans (8.4% vs. 8.6%, P=0.55) but nonrecommended use of
      antibiotics for the treatment of upper respiratory infection was higher in a
      managed care organization than a FFS private plan (31% vs. 21%, P=0.02). Rates of
      inappropriate myocardial perfusion imaging were similar in VA and private
      settings (22% vs. 16.6%, P=0.24), but rates of inappropriate surveillance
      endoscopy in the management of gastric ulcers were higher in the VA compared with
      private settings (37.4% vs. 20.4%-23.3%, P<0.0001). CONCLUSIONS: The available
      evidence is limited but there is no consistent evidence that any 1 system of care
      has been more effective at minimizing the overuse of health care services. More
      research is necessary to inform current health care reform efforts directed at
      reducing overuse.

PMID- 23552431
TI  - The patient-centered medical home: an evaluation of a single private payer
      demonstration in New Jersey.
AB  - BACKGROUND: The patient-centered medical home (PCMH) has increasingly been looked
      to by policy makers, health care providers, and private insurers as a potential
      solution to the fragmented and inefficient US health care system. Whether the
      PCMH achieves these goals is not known. OBJECTIVES: To evaluate a PCMH
      demonstration project implemented in 2011 in 8 New Jersey primary care practices
      covering over 10,000 plan members. RESEARCH DESIGN: We conduct difference-in
      differences analysis, comparing changes in outcomes at 8 medical home practices
      to a group of 24 comparison practices before (2010) and after (2011) the medical
      home implementation occurred. We use Mahalanobis distance matching to select the
      24 comparison practices, matching on practice characteristics. We focus on the
      effect of the PCMH pilot on 3 groups of outcomes: health care utilization, costs,
      and quality. RESULTS: The study cohort included 35,059 members during the study
      period 2010-2011-10,004 in the 8 PCMH practices and 25,055 in the 24 comparison
      practices. Health care utilization and costs did not significantly change with
      adoption of the PCMH model. In testing for changes in Healthcare Effectiveness
      and Data Information Set (HEDIS) quality measures, rates of mammography increased
      in PCMH practices after PCMH implementation compared to non-PCMH practices, by
      2.2 percentage points on a base of 69.5% (P<0.001). Rates of nephropathy
      screening also increased (by 6.6 percentage points on a base of 51.8%; P=0.05).
      Changes in 7 other HEDIS quality measures following PCMH implementation were not
      statistically significant. CONCLUSIONS: We find little evidence of reductions in
      health care utilization or cost and minimal evidence of improvements in quality
      of care. Ongoing work is needed to understand why this model of care seems to
      work in some cases and not others and to evaluate how to improve the medical
      home.

PMID- 23552432
TI  - In response.

PMID- 23552433
TI  - Improved coding of postoperative deep vein thrombosis and pulmonary embolism in
      administrative data (AHRQ Patient Safety Indicator 12) after introduction of new
      ICD-9-CM diagnosis codes.
AB  - BACKGROUND: Symptomatic venous thromboembolism is a common postoperative
      complication. The Agency for Healthcare Research and Quality (AHRQ) has developed
      a Patient Safety Indicator 12 to assist hospitals, payers, and other stakeholders
      to identify patients who experienced this complication. OBJECTIVES: To determine
      whether newly created and recently redefined ICD-9-CM codes improved the
      criterion validity of Patient Safety Indicator 12, based on new samples of
      records dated after October 2009. RESEARCH DESIGN, SUBJECTS, MEASURES: Two
      sources of data were used: (1) UHC retrospective case-control study of risk
      factors for acute symptomatic venous thromboembolism occurring within 90 days
      after total knee arthroplasty in teaching hospitals; (2) chart abstraction data
      by volunteer hospitals participating in the Validation Pilot Project of the AHRQ.
      RESULTS: In the UHC sample, the positive predictive value (PPV) was 99% (125/126)
      and the negative predictive value was 99.4% (460/463). In the AHRQ sample, the
      overall PPV was 81% (126/156). CONCLUSIONS: The PPV based on both samples shows
      substantial improvement compared with the previously reported PPVs of 43%-48%,
      suggesting that changes in ICD-9-CM code architecture and better coding guidance
      can improve the usefulness of coded data.

PMID- 23552434
TI  - Assessing low mortality in magnet hospitals.

PMID- 23552435
TI  - Using enriched observational data to develop and validate age-specific mortality
      risk adjustment models for hospitalized pediatric patients.
AB  - BACKGROUND: Growth and development in early childhood are associated with rapid
      physiological changes. We sought to develop and validate age-specific mortality
      risk adjustment models for hospitalized pediatric patients using objective
      physiological variables on admission in addition to administrative variables.
      METHODS: Age-specific laboratory and vital sign variables were crafted for
      neonates (up to 30 d old), infants/toddlers (1-23 mo), and children (2-17 y). We
      fit 3 logistic regression models, 1 for each age group, using a derivation cohort
      comprising admissions from 2000-2001 in 215 hospitals. We validated the models
      with a separate validation cohort comprising admissions from 2002-2007 in 62
      hospitals. We used the c statistic to assess model fit. RESULTS: The derivation
      cohort comprised 93,011 neonates (0.55% mortality), 46,152 infants/toddlers
      (0.37% mortality), and 104,010 children (0.40% mortality). The corresponding
      numbers of admissions (mortality rates) for the validation cohort were 162,131
      (0.50%), 33,818 (0.09%), and 73,362 (0.20%), respectively. The c statistics for
      the 3 models were 0.94, 0.91, and 0.92, respectively, for the derivation cohort
      and 0.91, 0.86, and 0.93, respectively, for the validation cohort. The relative
      contributions of physiological versus administrative variables to the model fit
      were 52% versus 48% (neonates), 93% versus 7% (infants/toddlers), and 82% versus
      18% (children). CONCLUSIONS: The thresholds for physiological determinants varied
      by age. Common physiological variables assessed on admission contributed
      significantly to predicting mortality for hospitalized pediatric patients. These
      models may have practical utility in risk adjustment for pediatric outcomes and
      comparative effectiveness research when physiological data are captured through
      the electronic medical record.

PMID- 23552436
TI  - Algorithm for identifying chemotherapy/biological regimens for metastatic colon
      cancer in SEER-Medicare.
AB  - BACKGROUND: Metastatic colon cancer (mCC) patients often receive multiple lines
      of chemotherapy/biological treatment (TX), yet subsequent TX lines have not been
      sufficiently examined using SEER-Medicare data. We developed an algorithm that
      identifies the number and type of TX lines received by mCC patients. METHODS: The
      algorithm rules for detecting TX lines were developed a priori and applied to
      SEER-Medicare data for 7951 elderly mCC patients, diagnosed in 2003-2007 and
      followed through 2009. Statistical analysis estimated the relationship between
      the number of treatments received and patient characteristics. Sensitivity
      analyses examined how results changed when different algorithm rules were used.
      RESULTS: Only 41% (3266) of mCC patients received any chemotherapy/biologics
      treatment; 1440 (18% of all, 44% of treated) and 274 (3% of all, 8% of treated)
      received second-line and third-line treatment, respectively. Initial and
      subsequent treatment regimens varied widely. Results were robust to alterations
      in the algorithm. CONCLUSIONS: The number of drugs used to treat cancer patients
      has increased during the past decade. Patients may have several TX lines with
      complex regimens. More guidance is needed with regard to identifying and studying
      these interventions using SEER-Medicare data. By proposing 1 approach to
      categorizing TX lines for mCC patients, we hope to empower the scientific
      community and to advance the use of SEER-Medicare data for health outcomes
      research.

PMID- 23552437
TI  - Predictive value of the present-on-admission indicator for hospital-acquired
      venous thromboembolism.
AB  - BACKGROUND: Hospital-acquired venous thromboembolic (HA-VTE) events are an
      important, preventable cause of morbidity and death, but accurately identifying
      HA-VTE events requires labor-intensive chart review. Administrative diagnosis
      codes and their associated "present-on-admission" (POA) indicator might allow
      automated identification of HA-VTE events, but only if VTE codes are accurately
      flagged "not present-on-admission" (POA=N). New codes were introduced in 2009 to
      improve accuracy. METHODS: We identified all medical patients with at least 1 VTE
      "other" discharge diagnosis code from 5 academic medical centers over a 24-month
      period. We then sampled, within each center, patients with VTE codes flagged
      POA=N or POA=U (insufficient documentation) and POA=Y or POA=W (timing clinically
      uncertain) and abstracted each chart to clarify VTE timing. All events that were
      not clearly POA were classified as HA-VTE. We then calculated predictive values
      of the POA=N/U flags for HA-VTE and the POA=Y/W flags for non-HA-VTE. RESULTS:
      Among 2070 cases with at least 1 "other" VTE code, we found 339 codes flagged
      POA=N/U and 1941 flagged POA=Y/W. Among 275 POA=N/U abstracted codes, 75.6% (95%
      CI, 70.1%-80.6%) were HA-VTE; among 291 POA=Y/W abstracted events, 73.5% (95% CI,
      68.0%-78.5%) were non-HA-VTE. Extrapolating from this sample, we estimated that
      59% of actual HA-VTE codes were incorrectly flagged POA=Y/W. POA indicator
      predictive values did not improve after new codes were introduced in 2009.
      CONCLUSIONS: The predictive value of VTE events flagged POA=N/U for HA-VTE was
      75%. However, sole reliance on this flag may substantially underestimate the
      incidence of HA-VTE.

PMID- 23552438
TI  - Does litigation increase or decrease health care quality?: a national study of
      negligence claims against nursing homes.
AB  - BACKGROUND: The tort system is supposed to help improve the quality and safety of
      health care, but whether it actually does so is controversial. Most previous
      studies modeling the effect of negligence litigation on quality of care are
      ecologic. OBJECTIVE: To assess whether the experience of being sued and incurring
      litigation costs affects the quality of care subsequently delivered in nursing
      homes. RESEARCH DESIGN, SUBJECTS, MEASURES: We linked information on 6471
      negligence claims brought against 1514 nursing homes between 1998 and 2010 to
      indicators of nursing home quality drawn from 2 US national datasets (Online
      Survey, Certification, and Reporting system; Minimum Data Set Quality
      Measure/Indicator Reports). At the facility level, we tested for associations
      between 9 quality measures and 3 variables indicating the nursing homes'
      litigation experience in the preceding 12-18 months (total indemnity payments;
      total indemnity payments plus administrative costs; >= 1 paid claims vs. none).
      The analyses adjusted for quality at baseline, case-mix, ownership, occupancy,
      year, and facility and state random effects. RESULTS: Nearly all combinations of
      the 3 litigation exposure measures and 9 quality measures--27 models in all-
      showed an inverse relationship between litigation costs and quality. However,
      only a few of these associations were statistically significant, and the effect
      sizes were very small. For example, a doubling of indemnity payments was
      associated with a 1.1% increase in the number of deficiencies and a 2.2% increase
      in pressure ulcer rates. CONCLUSIONS: Tort litigation does not increase the
      quality performance of nursing homes, and may decrease it slightly.

PMID- 23552439
TI  - Impact of socioeconomic adjustment on physicians' relative cost of care.
AB  - BACKGROUND: Ongoing efforts to profile physicians on their relative cost of care
      have been criticized because they do not account for differences in patients'
      socioeconomic status (SES). The importance of SES adjustment has not been
      explored in cost-profiling applications that measure costs using an episode of
      care framework. OBJECTIVES: We assessed the relationship between SES and episode
      costs and the impact of adjusting for SES on physicians' relative cost rankings.
      RESEARCH DESIGN: We analyzed claims submitted to 3 Massachusetts commercial
      health plans during calendar years 2004 and 2005. We grouped patients' care into
      episodes, attributed episodes to individual physicians, and standardized costs
      for price differences across plans. We accounted for differences in physicians'
      case mix using indicators for episode type and a patient's severity of illness. A
      patient's SES was measured using an index of 6 indicators based on the zip code
      in which the patient lived. We estimated each physician's case mix-adjusted
      average episode cost and percentile rankings with and without adjustment for SES.
      RESULTS: Patients in the lowest SES quintile had $80 higher unadjusted episode
      costs, on average, than patients in the highest quintile. Nearly 70% of the
      variation in a physician's average episode cost was explained by case mix of
      their patients, whereas the contribution of SES was negligible. After adjustment
      for SES, only 1.1% of physicians changed relative cost rankings >2 percentiles.
      CONCLUSIONS: Accounting for patients' SES has little impact on physicians'
      relative cost rankings within an episode cost framework.

PMID- 23552440
TI  - Long-term acute care and chronic critical illness.

PMID- 23552441
TI  - Association of adiponectin gene polymorphism with birth weight in Korean
      neonates.
AB  - Adiponectin has been associated with insulin resistance and type 2 diabetes
      mellitus and possibly fetal growth. Our aim was to assess the association between
      the single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and
      the birth sizes. We investigated four SNPs of ADIPOQ (rs182052, rs2241766,
      rs1501299, and rs266729) and birth height and weight in 237 healthy full-term
      neonates. The neonates with the rs182052 G allele had a greater birth weight (p =
      .043 in the dominant model) and a higher ponderal index (p = .028 in the additive
      model). The rs2241766 G allele was associated with a greater birth weight (p =
      .016 in the recessive model). In a logistic regression analysis, the homozygotes
      for the rs182052 G allele and those for the rs2241766 G allele showed a
      significant association with a greater birth weight above 90 percentile (OR 2.75,
      95% CI 1.13-6.70 and OR 5.15, 95% CI 1.66-15.99, respectively). In conclusion, we
      found an association between rs182052 and rs2241766 and birth weight and ponderal
      index among healthy neonates and suggested that adiponectin might have some roles
      in fetal growth.

PMID- 23552442
TI  - Finasteride for the treatment of hidradenitis suppurativa in children and
      adolescents.
AB  - IMPORTANCE: Hidradenitis suppurativa (HS) is a chronic debilitating cutaneous
      disease for which there is no universally effective treatment. Patients typically
      present at puberty with tender subcutaneous nodules that can progress to dermal
      abscess formation. Antiandrogens have been used in the treatment of HS, and
      studies have primarily focused on adult patients. OBSERVATIONS: We present a case
      series of 3 pediatric patients with HS who were successfully treated with oral
      finasteride, resulting in decreased frequency and severity of disease flares with
      no significant adverse effects. CONCLUSIONS AND RELEVANCE: Finasteride is a
      therapeutic option that provides benefit for pediatric patients with HS. Further
      prospective data and randomized controlled studies will provide helpful
      information in the management of this disease.

PMID- 23552443
TI  - Effect of cognitive reserve markers on Alzheimer pathologic progression.
AB  - Education, occupation, premorbid intelligence, and brain size are surrogate
      markers for cognitive reserve. Whether these markers have biological influence on
      Alzheimer disease (AD) pathology is not known. We thus aimed to investigate the
      effect of cognitive reserve proxies on longitudinal change of AD biomarkers. A
      total of 819 participants with normal cognition, mild cognitive impairment, and
      mild AD were enrolled in the Alzheimer's Disease Neuroimaging Initiative and
      followed up with repeated measures of cerebrospinal fluid, positron emission
      tomography, and magnetic resonance imaging biomarkers. Generalized estimating
      equations were used to assess whether biomarker rates of change were modified by
      reserve proxies. Cerebrospinal fluid Abeta42 decline was slower in normal
      cognition participants with higher cognitive reserve indexed by education,
      occupation, and American National Adult Reading Test (ANART). The decline of [F]
      fluorodeoxyglucose positron emission tomography uptake was slower in AD
      participants with better performance on the ANART. Education, occupation, and
      ANART did not modify the rates of magnetic resonance imaging hippocampal atrophy
      in any group. These findings remained unchanged after accounting for APOE 4,
      longitudinal missing data, and baseline cognitive performance. Higher levels of
      reserve markers may slow the rate of amyloid deposition before cognitive
      impairment and preserve glucose metabolism at the dementia stage over the course
      of AD pathologic progression. 

PMID- 23552444
TI  - Social competence at 6 months following childhood traumatic brain injury.
AB  - Children with traumatic brain injury (TBI) are at risk for social impairment.
      This study aimed to examine social function at 6 months post-TBI and to explore
      the contribution of injury, cognitive, and environmental influences. The sample
      included 136 children, 93 survivors of TBI, and 43 healthy controls. TBI
      participants were recruited on admission and underwent magnetic resonance imaging
      scan within 8 weeks of injury and behavioral assessment at 6 months post-injury.
      Healthy controls underwent magnetic resonance imaging scans and behavioral
      assessment on recruitment. Assessment included parent and child questionnaires
      tapping social outcome and child-direct testing of cognitive abilities important
      for social competence (communication, attention/executive function, social
      cognition). Injury characteristics and environmental measures were collected. At
      6-months post-injury, social problems were evident, but not global. Social
      participation appeared most vulnerable, with more severe injuries leading to
      greater problems. Greater injury severity and poorer communication skills were
      associated with poorer social adjustment and social participation, with the
      impact of family function also significant. Processing speed, younger age, and
      male gender also contributed to social outcomes. Further follow-up is required to
      track the recovery of social skills and the changing influences of cognition,
      brain, and environment over time.

PMID- 23552445
TI  - Sleep education in pediatric residency programs: a cross-cultural look.
AB  - BACKGROUND: The objective of this study was to assess the prevalence of education
      about sleep and sleep disorders in pediatric residency programs and to identify
      barriers to providing such education. METHODS: Surveys were completed by
      directors of 152 pediatric residency programs across 10 countries (Hong Kong,
      India, Indonesia, Japan, Singapore, South Korea, Thailand, United States-Canada,
      and Vietnam). RESULTS: Overall, the average amount of time spent on sleep
      education is 4.4 hours (median = 2.0 hours), with 23% responding that their
      pediatric residency program provides no sleep education. Almost all programs
      (94.8%) offer less than 10 hours of instruction. The predominant topics covered
      include sleep-related development, as well as normal sleep, sleep-related
      breathing disorders, parasomnias, and behavioral insomnia of childhood.
      CONCLUSIONS: These results indicate that there is still a need for more efforts
      to include sleep-related education in all pediatric residency programs, as well
      as coverage of the breadth of sleep-related topics. Such education would be
      consistent with the increased recognition of the importance of sleep and under
      diagnosis of sleep disorders in children and adolescents.

PMID- 23552446
TI  - Identification of compounds from Paris polyphylla (ChongLou) active against
      Dactylogyrus intermedius.
AB  - The present study was designated to ascertain the anthelmintic activity of the
      rhizomes of Paris polyphylla and to isolate and characterize the active
      constituents. The methanol extract from rhizomes of P. polyphylla showed
      significant anthelmintic activity against Dactylogyrus intermedius with the
      median effective concentration (EC50) 22.5 mg L(-1). Based on this finding, the
      methanol extract was fractionated by silica gel column chromatography in a
      bioassay-guided fractionation yielding 2 bioactive compounds, the structures of
      these compounds were elucidated as formosanin C and polyphyllin VII. The in vivo
      tests revealed that formosanin C and polyphyllin VII were significantly effective
      against D. intermedius with EC50 values of 0.6 and 1.2 mg L(-1), respectively.
      The acute toxicities (LC50) of formosanin C and polyphyllin VII for grass carp
      were 2.8 and 2.9 mg L(-1), respectively. The overall results provide important
      information for the potential application of formosanin C and polyphyllin VII in
      the therapy of serious infection caused by D. intermedius.

PMID- 23552447
TI  - Facile synthesis of the new tripodal tetraamine ligand tris(thiazolylmethyl)
      amine, and full characterization of two ferrous complexes.
AB  - We report in this communication the facile synthesis of the new
      tris(thiazolylmethyl)amine TTA ligand and the full characterization in solution
      and in the solid state of two ferrous complexes, [(TTA)FeCl2] and
      [(TTA)Fe(OTf)2]. TTA, the first example of a simple tris(thiazolemethyl)amine
      chelate--the second one only within this class of tripods--exerts a weak ligand
      field and the tertiary amine is weakly bound to the metal centre.

PMID- 23552451
TI  - Prenatal counseling and the detection of copy-number variants.

PMID- 23552448
TI  - Influence of deuteration in the glassing matrix on 13C dynamic nuclear
      polarization.
AB  - Replacement of protons by deuterons in the glassing solvents led to 2-3-fold
      improvement of the (13)C dynamic nuclear polarization (DNP) solid-state NMR
      signal for samples doped with large electron spin resonance (ESR) linewidth free
      radicals galvinoxyl, DPPH, and 4-oxo-TEMPO. Meanwhile, the reverse effect is
      observed for (13)C DNP using small ESR linewidth free radicals BDPA and trityl
      OX063.

PMID- 23552452
TI  - Response to Benn.

PMID- 23552453
TI  - Considering the cost of expanded carrier screening panels.

PMID- 23552454
TI  - Response to Stoll and Resta.

PMID- 23552456
TI  - Analysis of RNA base modification and structural rearrangement by single-molecule
      real-time detection of reverse transcription.
AB  - BACKGROUND: Zero-mode waveguides (ZMWs) are photonic nanostructures that create
      highly confined optical observation volumes, thereby allowing single-molecule
      resolved biophysical studies at relatively high concentrations of fluorescent
      molecules. This principle has been successfully applied in single-molecule, real
      time (SMRT(r)) DNA sequencing for the detection of DNA sequences and DNA base
      modifications. In contrast, RNA sequencing methods cannot provide sequence and
      RNA base modifications concurrently as they rely on complementary DNA (cDNA)
      synthesis by reverse transcription followed by sequencing of cDNA. Thus,
      information on RNA modifications is lost during the process of cDNA synthesis.
      RESULTS: Here we describe an application of SMRT technology to follow the
      activity of reverse transcriptase enzymes synthesizing cDNA on thousands of
      single RNA templates simultaneously in real time with single nucleotide turnover
      resolution using arrays of ZMWs. This method thereby obtains information from the
      RNA template directly. The analysis of the kinetics of the reverse transcriptase
      can be used to identify RNA base modifications, shown by example for N6
      methyladenine (m6A) in oligonucleotides and in a specific mRNA extracted from
      total cellular mRNA. Furthermore, the real-time reverse transcriptase dynamics
      informs about RNA secondary structure and its rearrangements, as demonstrated on
      a ribosomal RNA and an mRNA template. CONCLUSIONS: Our results highlight the
      feasibility of studying RNA modifications and RNA structural rearrangements in
      ZMWs in real time. In addition, they suggest that technology can be developed for
      direct RNA sequencing provided that the reverse transcriptase is optimized to
      resolve homonucleotide stretches in RNA.

PMID- 23552457
TI  - Hopping and diffusion of ultrasoft particles in cluster crystals in the explicit
      presence of a solvent.
AB  - We have investigated diffusion and hopping processes in a cluster crystal formed
      from mesoscopic, ultrasoft particles. In contrast to previous contributions we
      have explicitly included in our investigations the microscopic solvent by using a
      simulation scheme that takes the induced hydrodynamic interactions into account
      as faithfully as possible. In our investigations we first focused on the
      processes of migration of the ultrasoft particles. By evaluating dynamical
      correlation functions we were able to demonstrate that the presence of the
      solvent does indeed have an important impact on the diffusion and hopping
      processes of the particles: this applies in particular to the diffusive
      behaviour, to the angular orientation of the jump events and to the spatial
      extents of these events. In a second set-up we have added non-cluster-forming
      ultrasoft particles to the system, investigating thus the impact of the solvent
      and that of the mutual interaction of the two species of ultrasoft particles on
      their respective dynamic behaviours. Our investigations clearly demonstrate,
      beside the expected significant role that the solvent plays in this set-up, that
      diffusion and the jump processes show distinct differences for the two particle
      species.

PMID- 23552459
TI  - Mesoscopic modelling of frustration in microemulsions.
AB  - The swelling behaviour of water-oil microemulsions - considering a surfactant
      layer between oil and water - has been studied using a two level-cuts Gaussian
      random field approach based on the Helfrich formalism. Microstructures and
      scattering properties of microemulsions have been calculated for different
      amounts of oil (and water) for flexible and rigid microemulsions. When the
      stiffness, the spontaneous curvature of the interfacial film, and the surface to
      volume ratio of the immiscible fluids are varied, the microemulsion topology and
      morphology change in order to minimize the microemulsion free energy. Our
      simulations point out a change in the microemulsion morphology as a function of
      the surfactant film rigidity and the composition of oil, water and the
      surfactant. Locally lamellar structures are found for rigid microemulsions,
      whereas for more flexible ones, the connected-droplet and/or bicontinuous
      structures are preferred. Furthermore, we show that the microemulsion swelling
      versus the volume fraction gives a specific signature of the microemulsion
      microstructure. This allows for discriminating between different types of
      microemulsions: flexible, frustrated and unfrustrated (close to bi-liquid foams),
      and connected structures as molten hexagonal and cubic phases. The universal
      swelling behaviour is compared to different analytic expressions of Disordered
      Open Connected (DOC) models for the microemulsion swelling versus the volume
      fraction.

PMID- 23552461
TI  - Ups and downs of improving physical examination access for patients and
      physicians.

PMID- 23552460
TI  - Climate change, human health, and biomedical research: analysis of the National
      Institutes of Health research portfolio.
AB  - BACKGROUND: According to a wide variety of analyses and projections, the
      potential effects of global climate change on human health are large and diverse.
      The U.S. National Institutes of Health (NIH), through its basic, clinical, and
      population research portfolio of grants, has been increasing efforts to
      understand how the complex interrelationships among humans, ecosystems, climate,
      climate variability, and climate change affect domestic and global health.
      OBJECTIVES: In this commentary we present a systematic review and categorization
      of the fiscal year (FY) 2008 NIH climate and health research portfolio. METHODS:
      A list of candidate climate and health projects funded from FY 2008 budget
      appropriations were identified and characterized based on their relevance to
      climate change and health and based on climate pathway, health impact, study
      type, and objective. RESULTS: This analysis identified seven FY 2008 projects
      focused on climate change, 85 climate-related projects, and 706 projects that
      focused on disease areas associated with climate change but did not study those
      associations. Of the nearly 53,000 awards that NIH made in 2008, approximately
      0.17% focused on or were related to climate. CONCLUSIONS: Given the nature and
      scale of the potential effects of climate change on human health and the degree
      of uncertainty that we have about these effects, we think that it is helpful for
      the NIH to engage in open discussions with science and policy communities about
      government-wide needs and opportunities in climate and health, and about how
      NIH's strengths in human health research can contribute to understanding the
      health implications of global climate change. This internal review has been used
      to inform more recent initiatives by the NIH in climate and health.

PMID- 23552462
TI  - Melanoma simulation model: promoting opportunistic screening and patient
      counseling.
AB  - IMPORTANCE: Lack of training hampers melanoma recognition by physicians.
      OBJECTIVE: To evaluate a melanoma simulation model to teach visual assessment and
      counseling skills. DESIGN AND SETTING: Simulation model study in an academic
      research setting. PARTICIPANTS: A convenience sample of third-year medical
      students was randomly assigned to receive the intervention before or after a
      standardized patient. INTERVENTION: During the primary care clerkship, medical
      students participated in melanoma skills training using 2 simulation models
      replicating melanomas and abnormal or benign nevi. Scoring threshold rules for
      visual assessment and management of pigmented lesions and videos of patient
      counseling were provided. MAIN OUTCOME MEASURES: Identifying a melanoma moulage
      and counseling the standardized patient. Secondary measures were preintervention
      and 2-week postintervention knowledge, attitudes about and confidence in their
      ability to perform opportunistic surveillance and counseling, as well as
      identification on the model of clinically suspicious pigmented lesions, lesions
      needing a biopsy, and lesions to be monitored for change. RESULTS Among 74
      students, confidence in their ability to perform opportunistic surveillance
      improved significantly after skills training (P < .05, chi2 test). Monitoring
      clinically suspicious lesions for change decreased from 16% (12 of 74) to 3% (2
      of 74) and performing a biopsy increased from 80% (59 of 74) to 96% (71 of 74),
      monitoring benign lesions for change decreased from 43% (32 of 74) to 3% (2 of
      74), and biopsying melanoma in situ increased from 10% (7 of 74) to 26% (20 of
      74) (P < .05 for all, chi2 test). Detection of the melanoma moulage on the
      standardized patient occurred more often by trained students (P < .05, chi2
      test). CONCLUSION AND RELEVANCE: A 1-hour melanoma simulation education and
      skills training experience improved performance of opportunistic surveillance,
      management, and patient counseling by third-year medical students. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01191294.

PMID- 23552463
TI  - Upper endoscopy for gastroesophageal reflux disease.

PMID- 23552464
TI  - Prepulse inhibition in HIV-associated neurocognitive disorders.
AB  - Sensorimotor inhibition, or the ability to filter out excessive or irrelevant
      information, theoretically supports a variety of higher-level cognitive
      functions. Impaired inhibition may be associated with increased impulsive and
      risky behavior in everyday life. Individuals infected with HIV frequently show
      impairment on tests of neurocognitive function, but sensorimotor inhibition in
      this population has not been studied and may be a contributor to the profile of
      HIV-associated neurocognitive disorders (HAND). Thirty-seven HIV-infected
      individuals (15 with HAND) and 48 non-infected comparison subjects were assessed
      for prepulse inhibition (PPI), an eyeblink startle paradigm measuring
      sensorimotor gating. Although HIV status alone was not associated with PPI
      deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI
      compared to cognitively intact HIV-positive subjects. In HIV-positive subjects,
      PPI was correlated with working memory but was not associated with antiretroviral
      therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV
      accompanies deficits in higher-order cognitive functions, although the causal
      direction of this relationship requires investigation. Subsequent research on the
      role of sensorimotor gating on decision-making and risk behaviors in HIV may be
      indicated.

PMID- 23552465
TI  - MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness?
AB  - Recently, the hypothesis that colorectal tumors originate from a subpopulation of
      cells called 'cancer stem cells' (CSCs) or tumor-initiating cells, which exhibit
      stem-like features, has been confirmed experimentally in various human cancers.
      Several studies have confirmed the existence of colorectal CSCs (CRCSCs) and have
      demonstrated that this rare cell population can be isolated by the expression of
      specific cell surface biomarkers. MicroRNAs (miRNAs) are a class of small non
      coding RNAs, which are crucial for post-transcriptional regulation of gene
      expression and participate in a wide variety of biological functions, including
      development, cell proliferation, differentiation, metabolism and signal
      transduction. Moreover, new evidences suggest that miRNAs could contribute to
      preserve stemness of embryonic stem cells and could be involved in maintaining
      stemness of CSCs. Recent studies have begun to outline the role of miRNAs in
      regulation of CRCSCs. This review aims to summarize the recent advancement about
      the roles of miRNAs in CRCSCs that may represent a step forward in understanding
      the molecular mechanisms and the possible approaches for colorectal cancer
      therapy.

PMID- 23552466
TI  - Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer.
AB  - Claudins are integral tight junction proteins that are responsible for
      maintaining the integrity of epithelial cell architecture and cell polarity.
      Claudin-3 and -4 are overexpressed in several cancers and have been shown to act
      as receptors for the Clostridium perfringens enterotoxin (CPE), a toxin that
      causes rapid cell lysis. CPE has demonstrated effectiveness in treating several
      different cancers in mouse models, provided that these cancers express claudin-3
      or claudin-4. Here, we show that claudin-3/4 expression is not an absolute
      requirement for CPE action and, through overexpression and knockdown experiments,
      we identify claudin-6 as a novel functional receptor for CPE. Indeed, UCI-101, an
      ovarian cancer cell line highly sensitive to CPE, does not express claudin-3/4
      and knockdown of claudin-6 in these cells decreases CPE sensitivity. Moreover,
      two different ovarian cell lines that are resistant to the effects of CPE can be
      made sensitive through claudin-6 overexpression. Binding assays show that CPE can
      indeed bind claudin-6 in cells and that this binding is associated with CPE
      cytotoxicity. Multicellular tumor spheroids experiments demonstrate that claudin
      6 can also be a target of CPE in three-dimensional cultures. Our data establish
      claudin-6 as a novel receptor for CPE and introduces the possibility of a novel
      targeted therapeutic for ovarian and other cancers that express claudin-6.

PMID- 23552467
TI  - Multiple receptor tyrosine kinases promote the in vitro phenotype of metastatic
      human osteosarcoma cell lines.
AB  - The survival rate for osteosarcoma patients with localized disease is 70% and
      only 25% for patients with metastases. Therefore, novel therapeutic and
      prognostic tools are needed. In this study, extensive screening and validation
      strategies identified Axl, EphB2, FGFR2, IGF-1R and Ret as specific receptor
      tyrosine kinases (RTKs) that are activated and promote the in vitro phenotype of
      two genetically different metastatic osteosarcoma cell lines. Initial
      phosphoproteomic screening identified twelve RTKs that were phosphorylated in
      143B and/or LM7 metastatic human osteosarcoma cells. A small interfering RNA
      (siRNA) screen demonstrated that siRNA pools targeting ten of the twelve RTKS
      inhibited the in vitro phenotype of one or both cell lines. To validate the
      results, we individually tested the four siRNA duplexes that comprised each of
      the effective siRNA pools from the initial screen. The pattern of phenotype
      inhibition replicated the pattern of mRNA knockdown by the individual duplexes
      for seven of the ten RTKs, indicating the effects are consistent with on-target
      silencing. Five of those seven RTKs were further validated using independent
      approaches including neutralizing antibodies (IGF-1R), antisense-mediated
      knockdown (EphB2, FGFR2, and Ret) or small molecule inhibitors (Axl), indicating
      that those specific RTKs promote the in vitro behavior of metastatic osteosarcoma
      cell lines and are potential therapeutic targets for osteosarcoma.
      Immunohistochemistry demonstrated that Axl is frequently activated in
      osteosarcoma patient biopsy samples, further supporting our screening and
      validation methods to identify RTKs that may be valuable targets for novel
      therapies for osteosarcoma patients.

PMID- 23552469
TI  - Chemotherapy in metastatic renal cell carcinoma today? A systematic review.
AB  - The prognosis of patients affected by metastatic renal cell carcinoma (mRCC) has
      improved markedly with targeted therapies. Unfortunately, 20-25% of the patients
      are refractory to treatment at the first response assessment and most patients
      will acquire drug resistance during the treatment. Moreover, current data on the
      clinical activity of targeted agents in poor risk or non-clear-cell mRCC patients
      are inconclusive because of the absence of prospective trials. Therefore, there
      are still several patients in need of new therapeutic approaches to improve
      clinical outcomes. Kidney cancer is historically considered resistant to
      chemotherapy on the basis that the results of phase II trials have not always
      been promising. We carried out a systematic review of both monochemotherapy and
      polychemotherapy alone or combined with immunotherapy or targeted agents in mRCC
      to define the state of the art and to evaluate further clinical research fields.
      All retrospectives, phase I/dose finding, phase II and phase III studies on
      chemotherapy in mRCC, published in the literature from January 2003 to November
      2012, with at least 20 patients enrolled, were evaluated. Although the results of
      clinical trials have often been disappointing, in selected cases of mRCC,
      chemotherapy may have a promising antitumor activity, particularly when there are
      sarcomatoid differentiation features, or in highly progressive disease where the
      combination of doxorubicine plus gemcitabine or capecitabine has yielded
      interesting results. Chemotherapy may play a role in mRCC, whereas targeted
      agents and immunotherapy have not yielded durable and satisfactory results;
      further studies are needed.

PMID- 23552470
TI  - Phase I and pharmacokinetic study of bexarotene in combination with gefitinib in
      the third-line treatment of non-small-cell lung cancer: brief report.
AB  - Gefitinib (an epidermal growth factor receptor tyrosine kinase inhibitor) and
      bexarotene (a rexinoid) affect similar oncogenic pathways and are both
      metabolized through cytochrome P450 CYP3A4. We studied the combination of
      bexarotene and gefitinib in the third-line treatment of advanced non-small-cell
      lung cancer to examine pharmacokinetic interactions and establish the maximum
      tolerated dose. This was a single-institution, nonrandomized, open-label, phase I
      clinical trial with a standard 3+3 dose escalation. Three patients were enrolled
      at each dose level on the basis of pharmacokinetic analysis with dose level 1
      including gefitinib (Iressa) 250 mg oral daily and bexarotene (Targretin) 400
      mg/m oral daily and dose level +1 including gefitinib 500 mg oral daily and
      bexarotene 400 mg/m oral daily. Patients received gefitinib alone for 2 weeks to
      allow for steady state and thereafter, bexarotene was added. In dose level 1, two
      of three patients had undetectable gefitinib levels at day 15 for unknown
      reasons. However, the peak levels on day 29 for all three patients receiving 250
      mg of gefitinib with bexarotene are lower than published peak levels. Among the
      three patients in dose level +1, ~40% lower gefitinib plasma concentrations were
      noted on day 29 compared with day 15 along with a mean 44% reduction in area
      under the plasma concentration-time curve from 0 to 24 h (AUC0-24). Bexarotene
      appears to lower the C max and AUC0-24 of gefitinib through cytochrome P450
      CYP3A4. Our results have pharmacokinetic implications for ongoing trials that
      combine bexarotene with other small molecules in the era of personalized cancer
      therapy. 

PMID- 23552468
TI  - The 'N-factors' in pancreatic cancer: functional relevance of NF-kappaB, NFAT and
      Nrf2 in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest
      malignancies, with an overall life expectancy of 6 months. Despite considerable
      advances in the understanding of the molecular mechanisms involved in the
      carcinogenesis of PDAC, the outcome of the disease was not significantly improved
      over the last 20 years. Although some achievements in molecular-targeted
      therapies have been made (that is, targeting the epidermal growth factor receptor
      by erlotinib), which already entered clinical settings, and despite the promising
      outcome of the FOLFIRINOX trial, there is an urgent need for improvement of the
      chemotherapy in this disease. A plethora of molecular alterations are thought to
      be responsible for the profound chemoresistance, including mutations in oncogenes
      and tumor suppressors. Besides these classical hallmarks of cancer, the
      constitutive or inducible activity of transcription factor pathways are
      characteristic changes in PDAC. Recently, three transcription factors-nuclear
      factor-kappaB (NF-kappaB), nuclear factor of activated T cells (NFAT) and nuclear
      factor-E2-related factor-2 (Nrf2)-have been shown to be crucial for tumor
      development and chemoresistance in pancreatic cancer. These transcription factors
      are key regulators of a variety of genes involved in nearly all aspects of
      tumorigenesis and resistance against chemotherapeutics and death receptor
      ligands. Furthermore, the pathways of NF-kappaB, NFAT and Nrf2 are functional,
      interacting on several regulatory steps, and, especially, natural compounds such
      as curcumin interfere with more than one pathway. Thus, targeting these pathways
      by established inhibitors or new drugs might have great potential to improve the
      outcome of PDAC patients, most likely in combination with established anticancer
      drugs. In this article, we summarize recent progress in the characterization of
      these transcription-factor pathways and their role in PDAC and therapy
      resistance. We also discuss future concepts for the treatment of PDAC relying on
      these pathways.

PMID- 23552471
TI  - Fengycin inhibits the growth of the human lung cancer cell line 95D through
      reactive oxygen species production and mitochondria-dependent apoptosis.
AB  - To investigate the antitumor activity and action mechanism of fengycin using the
      human lung cancer cell line 95D. The antitumor activity of fengycin was tested in
      vitro and in vivo. Reactive oxygen species production, Ca(2+) uptake, and
      mitochondrial membrane potential loss induced by fengycin in 95D cells were
      measured by flow cytometry and a laser confocal microscope. Lactate dehydrogenase
      release and caspase activity in fengycin-treated 95D cells were assayed using
      cytotoxicity detection kits. Apoptosis triggered by fengycin was identified by
      4,6-diamidino-2-phenylindole (DAPI) staining and flow cytometry. The effects of
      fengycin on cell-cycle and apoptosis-related proteins were evaluated by
      quantitative reverse-transcription PCR and western blot. Treatment with fengycin
      not only significantly decreased cell proliferation in various cancer cell lines
      including 95D but inhibited the growth of xenografted 95D cells in nude mice.
      Fengycin also induced reactive oxygen species production and Ca(2+) uptake, as
      well as lactate dehydrogenase release and mitochondrial membrane potential loss.
      Further experiments showed that fengycin could trigger apoptosis in 95D cells and
      cause cell-cycle arrest at the G0/G1 stage by downregulating cyclin D1 and cyclin
      dependent kinase 4 (CDK4). While investigating caspase activity and the
      expression of apoptosis-related proteins, fengycin was found to induce apoptosis
      in 95D cells through the mitochondrial pathway, evidenced by increased caspase
      activity, Bax expression, and cytochrome c release into the cytoplasm, as well as
      decreased Bcl-2 levels. Fengycin can inhibit the growth of the cancer cell line
      95D by regulating the cell cycle and promoting apoptosis, suggesting that it may
      have potential as an anticancer treatment.

PMID- 23552472
TI  - Expression and prognostic value of VEGFR-2, PDGFR-beta, and c-Met in advanced
      hepatocellular carcinoma.
AB  - BACKGROUND: We explore the clinical and prognostic significance of expression of
      vascular endothelial growth factor receptor (VEGFR)-2, platelet-derived growth
      factor receptor (PDGFR)-beta, and c-Met in patients with hepatocellular carcinoma
      (HCC). METHODS: The expression of VEGFR-2, PDGFR-beta, and c-Met were determined
      by immunohistochemical examination of the tissues of 93 HCC patients. The
      relationships of these markers with clinicopathological factors and prognosis
      were then analyzed. RESULTS: High expression of VEGFR-2, PDGFR-beta, and c-Met
      was found in 86%, 19.4%, and 80.6% of patients, respectively. Expression of VEGFR
      2 correlated with gender (P = 0.044), hepatitis B surface antigen positivity (P =
      0.024), degree of tumor differentiation (P = 0.023), and hepatic cirrhosis (P =
      0.026). Expression of PDGFR-beta correlated with alpha-fetoprotein level (P =
      0.029), tumor size (P = 0.033), and hepatic cirrhosis (P = 0.023). No significant
      correlations were identified between expression of c-Met and clinicopathological
      factors. Expression of PDGFR-beta correlated with overall survival (P = 0.046)
      and expression of c-Met correlated with progression-free survival (P = 0.01).
      CONCLUSIONS: We found that in patients with HCC, high expression of VEGFR-2
      correlates with chronic hepatitis B virus infection and hepatic cirrhosis. High
      expression of PDGFR-beta is a predictor of poor prognosis. High expression of C
      Met may predict therapeutic effectiveness of sorafenib in HCC patients.

PMID- 23552473
TI  - Immunotargeting and eradication of orthotopic melanoma using a chemokine-enhanced
      DNA vaccine.
AB  - DNA vaccines are attractive candidates for tumor immunotherapy. However, the
      potential of DNA vaccines in treating established malignant lesions has yet to be
      demonstrated. Here we demonstrate that transient alteration of either
      intratumoral or intradermal (ID) chemotactic gradients provide a favorable milieu
      for DNA vaccine-mediated activation of tumor-specific immune response in both
      prophylactic and therapeutic settings. Specifically, we show that priming of
      established B16 ID melanoma lesions via forced intratumoral expression of CCL21
      boosted DNA vaccination-dependent systemic cytotoxic immune response leading to
      the regression of tumor nodules. In this setting, application of CCL20 was not
      effective likely due to the engagement of the regulatory T cells. However,
      priming of the skin at DNA vaccine administration sites outside the tumor bed
      with both CCL20 and CCL21 chemokines along with structural modifications of the
      DNA vaccine significantly improved vaccine efficacy. This optimized ID
      vaccination regimen led to the inhibition of distant established melanomas and
      prolonged tumor-free survival of mice observed in 60% of vaccinated animals with
      complete tumor remission in 30%. These effects were mediated by extranodal
      priming and activation of T cells at vaccine administration sites and progressive
      accumulation of systemic antigen-specific cytotoxic T cells (CTLs) on successive
      vaccinations. These results underscore the potential of chemokine-enhanced DNA
      vaccination to mount therapeutic immune response against established tumors.

PMID- 23552474
TI  - Evidence for direct transmission of the cat lungworm Troglostrongylus brevior
      (Strongylida: Crenosomatidae).
AB  - Metastrongyloids of cats are emerging pathogens that may cause fatal broncho
      pulmonary disease. Infestation of definitive hosts occurs after ingestion of
      intermediate or paratenic hosts. Among metastrongyloids of cats, Troglostrongylus
      brevior and Troglostrongylus subcrenatus (Strongylida: Crenosomatidae) have
      recently been described as agents of severe broncho-pulmonary disease. Here, we
      provide, for the first time, observational evidence suggesting the direct
      transmission of T. brevior from queen cat to suckling kittens. This new knowledge
      will have a significant impact on current scientific information of this parasite
      and shed new light into the biology and epidemiology of metastrongyloid
      nematodes.

PMID- 23552475
TI  - Effective isotropic potential for dipolar hard spheres.
AB  - A new effective isotropic potential is proposed for the dipolar hard-sphere
      fluid, on the basis of recent results by others for its angle-averaged radial
      distribution function. The new effective potential is shown to exhibit
      oscillations even for moderately high densities and moderately strong dipole
      moments, which are absent from earlier effective isotropic potentials. The
      validity and significance of this result are briefly discussed.

PMID- 23552476
TI  - A TRLFS study on the complexation of novel BTP type ligands with Cm(III).
AB  - Two BTP-type N-donor ligands with different numbers of aromatic nitrogen atoms
      (2,6-bis(4-ethyl-pyridazin-1-yl)pyridine, Et-BDP and 2,6-bis(4-(n)propyl-2,3,5,6
      tetrazine-1-yl)pyridine, (n)Pr-Tetrazine) have been synthesized and characterized
      by NMR and MS techniques. The complexation with Cm(III) in 2-propanol-water (1 :
      1, vol.) is studied for both ligands using time resolved laser-induced
      fluorescence spectroscopy (TRLFS) and the complexation properties are compared to
      (n)Pr-BTP. With increasing the ligand concentration three different species, the
      1 : 1-, 1 : 2- and 1 : 3-complex, were found. Log beta3 values of 7.6 for the
      formation of Cm(Et-BDP)3 and 9.2 for the formation of Cm((n)Pr-Tetrazine)3 are
      determined. The complexation with (n)Pr-Tetrazine shows slow kinetics.
      Thermodynamic data of the complexation reactions are determined in a temperature
      range of 25  degrees C-60  degrees C. The complexation with Et-BDP is exothermic
      (DeltaH = -16.3 +/- 1.2 kJ mol(-1)) and exergonic (DeltaG = -43.8 +/- 2.6 kJ mol(
      1)) whereas the complexation with (n)Pr-Tetrazine is endothermic (DeltaH = 43.9
      +/- 3.1 kJ mol(-1)) and exergonic (DeltaG = -51.7 +/- 2.2 kJ mol(-1)). In the
      case of the latter the complexation is driven by a highly positive reaction
      entropy change (DeltaS = 320.6 +/- 15.4 J mol(-1) K(-1)). In comparison to (n)Pr
      BTP, less negative DeltaG values were found for the complexation of Cm(III) with
      both ligands.

PMID- 23552477
TI  - Moving pieces.

PMID- 23552479
TI  - A novel therapeutic combination approach for treating multiple vemurafenib
      induced keratoacanthomas: systemic acitretin and intralesional fluorouracil.

PMID- 23552480
TI  - Vitrification preserves chromatin integrity, bioenergy potential and oxidative
      parameters in mouse embryos.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of vitrification on
      morpho-functional parameters (blastomere/chromatin integrity and
      bioenergy/oxidative potential) of mouse preimplantation embryos. METHODS: In vivo
      produced mouse (4/16-cell, morulae and blastocyst-stage) embryos were randomly
      divided into vitrification and control groups. For vitrification, embryos were
      exposed to a 2-step loading of ethylene glycol and propylene glycol, before being
      placed in a small nylon loop and submerged into liquid nitrogen. After warming,
      the cryoprotectants were diluted by a 3-step procedure. Embryo morphology,
      chromatin integrity and energy/oxidative status were compared between groups.
      RESULTS: Vitrification induced low grade blastomere cytofragmentation (P < 0.05)
      and low chromatin damage only in embryos at the morula stage (P < 0.001).
      Mitochondrial (mt) distribution pattern was affected by vitrification only in
      early embryos (P < 0.001). Mitochondrial activity did not change upon
      vitrification in morula-stage embryos but it was reduced in blastocyst-stage
      embryos (P < 0.05). Intracellular ROS levels significantly increased in embryos
      at the morula and blastocyst stages (P < 0.001). Colocalization of active
      mitochondria and ROS increased only in vitrified blastocysts. CONCLUSIONS: In
      conclusion, this study elucidates the developmentally-related and mild effects of
      vitrification on morphology, nuclear and bioenergy/oxidative parameters of mouse
      embryos and demonstrates that vitrification is a suitable method for preserving
      predictive parameters of embryo ability to induce a full-term pregnancy.

PMID- 23552482
TI  - Comparing molecular photofragmentation dynamics in the gas and liquid phases.
AB  - This article explores the extent to which insights gleaned from detailed studies
      of molecular photodissociations in the gas phase (i.e. under isolated molecule
      conditions) can inform our understanding of the corresponding photofragmentation
      processes in solution. Systems selected for comparison include a thiophenol (p
      methylthiophenol), a thioanisole (p-methylthioanisole) and phenol, in vacuum and
      in cyclohexane solution. UV excitation in the gas phase results in RX-Y (X = O,
      S; Y = H, CH3) bond fission in all cases, but over timescales that vary by ~4
      orders of magnitude - all of which behaviours can be rationalised on the basis of
      the relevant bound and dissociative excited state potential energy surfaces
      (PESs) accessed by UV photoexcitation, and of the conical intersections that
      facilitate radiationless transfer between these PESs. Time-resolved UV pump
      broadband UV/visible probe and/or UV pump-broadband IR probe studies of the
      corresponding systems in cyclohexane solution reveal additional processes that
      are unique to the condensed phase. Thus, for example, the data clearly reveal
      evidence of (i) vibrational relaxation of the photoexcited molecules prior to
      their dissociation and of the radical fragments formed upon X-Y bond fission, and
      (ii) geminate recombination of the RX and Y products (leading to reformation of
      the ground state parent and/or isomeric adducts). Nonetheless, the data also show
      that, in each case, the characteristics (and the timescale) of the initial bond
      fission process that occurs under isolated molecule conditions are barely changed
      by the presence of a weakly interacting solvent like cyclohexane. These condensed
      phase studies are then extended to an ether analogue of phenol (allyl phenyl
      ether), wherein UV photo-induced RO-allyl bond fission constitutes the first step
      of a photo-Claisen rearrangement.

PMID- 23552483
TI  - WHO shows it cares about hearing loss.

PMID- 23552484
TI  - Linking interfacial chemistry of CO2 to surface structures of hydrated metal
      oxide nanoparticles: hematite.
AB  - A better understanding of interaction with dissolved CO2 is required to
      rationally design and model the (photo)catalytic and sorption processes on metal
      (hydr)oxide nanoparticles (NPs) in aqueous media. Using in situ FTIR
      spectroscopy, we address this problem for rhombohedral 38 nm hematite (alpha
      Fe2O3) nanoparticles as a model. We not only resolve the structures of the
      adsorbed carbonate species, but also specify their adsorption sites and their
      location on the nanoparticle surface. The spectral relationships obtained present
      a basis for a new method of characterizing the microscopic structural and acid
      base properties (related to individual adsorption sites) of hydrated metal
      (hydr)oxide NPs using atmospherically derived CO2 as a probe. Specifically, we
      distinguish two carbonate species suggesting two principally different adsorption
      mechanisms. One species, which is more weakly adsorbed, has an inner-sphere
      mononuclear monodentate structure which is formed by a conventional ligand
      exchange mechanism. At natural levels of dissolved carbonate and pH from 3 to 11,
      this species is attached to the most acidic/reactive surface cations (surface
      states) associated with ferrihydrite-like surface defects. The second species,
      which is more strongly adsorbed, presents a mixed C and O coordination of bent
      CO2. This species uniquely recognizes the stoichiometric rhombohedral {104}
      facets in the NP texture. Like in gas phase, it is formed through the surface
      coordination of molecular CO2. We address how the adsorption sites hosting these
      two carbonate species are affected by the annealing and acid etching of the NPs.
      These results support the nanosize-induced phase transformation of hematite
      towards ferrihydrite under hydrous conditions, and additionally show that the
      process starts from the roughened areas of the facet intersections.

PMID- 23552485
TI  - Author reply: To PMID 23208168.

PMID- 23552486
TI  - Are empirically-derived subtypes of mild cognitive impairment consistent with
      conventional subtypes?
AB  - Given the importance of identifying dementia prodromes for future treatment
      efforts, we examined two methods of diagnosing mild cognitive impairment (MCI)
      and determined whether empirically-derived MCI subtypes of these diagnostic
      methods were consistent with one another as well as with conventional MCI
      subtypes (i.e., amnestic, non-amnestic, single-domain, multi-domain).
      Participants were diagnosed with MCI using either conventional Petersen/Winblad
      criteria (n = 134; >1.5 SDs below normal on one test within a cognitive domain)
      or comprehensive neuropsychological criteria developed by Jak et al. (2009) (n =
      80; >1 SD below normal on two tests within a domain), and the resulting samples
      were examined via hierarchical cluster and discriminant function analyses.
      Results showed that neuropsychological profiles varied depending on the criteria
      used to define MCI. Both criteria revealed an Amnestic subtype, consistent with
      prodromal Alzheimer's disease (AD), and a Mixed subtype that may capture
      individuals in advanced stages of MCI. The comprehensive criteria uniquely
      yielded Dysexecutive and Visuospatial subtypes, whereas the conventional criteria
      produced a subtype that performed within normal limits, suggesting its
      susceptibility to false positive diagnostic errors. Whether these empirically
      derived MCI subtypes correspond to dissociable neuropathologic substrates and
      represent reliable prodromes of dementia will require additional follow-up.

PMID- 23552487
TI  - Serum-stimulated cell cycle entry promotes ncOGT synthesis required for cyclin D
      expression.
AB  - Nuclear and cytoplasmic O-GlcNAc transferase (OGT) is a unique and universally
      expressed enzyme catalyzing O-GlcNAcylation of thousands of proteins. Although
      OGT interferes with many crucial intracellular processes, including cell cycle,
      only few studies have focused on elucidating the precise role of the
      glycosyltransferase during cell cycle entry. We first demonstrated that starved
      MCF7 cells reincubated with serum quickly induced a significant OGT increase
      concomitantly to activation of PI3K and MAPK pathways. Co-immunoprecipitation
      experiments performed upon serum stimulation showed a progressive interaction
      between OGT and beta-catenin, a major factor in the regulation of cell cycle. OGT
      expression was also observed in starved HeLa cells reincubated with serum. In
      these cells, the O-GlcNAcylation status of the beta-catenin-2XFLAG was increased
      following stimulation. Moreover, beta-catenin-2XFLAG was heavily O-GlcNAcylated
      in exponentially proliferating HeLa cells when compared to confluent cells.
      Furthermore, blocking OGT activity using the potent inhibitor Ac-5SGlcNAc
      prevented serum-stimulated cyclin D1 synthesis and slightly delayed cell
      proliferation. At last, interfering with OGT expression (siOGT) blocked cyclin D1
      expression and decreased PI3K and MAPK activation. Together, our data indicate
      that expression and catalytic activity of OGT are necessary and essential for
      G0/G1 transition.

PMID- 23552491
TI  - Diversity of transposable elements and repeats in a 600 kb region of the fly
      Calliphora vicina.
AB  - BACKGROUND: Transposable elements (TEs) are a very dynamic component of
      eukaryotic genomes with important implications (e.g., in evolution) and
      applications (e.g., as transgenic tools). They also represent a major challenge
      for the assembly and annotation of genomic sequences. However, they are still
      largely unknown in non-model species. RESULTS: Here, we have annotated the
      repeats and transposable elements present in a 600 kb genomic region of the
      blowfly Calliphora vicina (Diptera: Calliphoridae) which contains most of the
      achaete-scute gene complex of this species. This is the largest genomic region to
      be sequenced and analyzed in higher flies outside the Drosophila genus. We find
      that the repeat content spans at least 24% of the sequence. It includes 318
      insertions classified as 3 LTR retrotransposons, 21 LINEs, 14 cut-and-paste DNA
      transposons, 4 helitrons and 33 unclassified repeats. CONCLUSIONS: This is the
      most detailed description of TEs and repeats in the Calliphoridae to date. This
      contribution not only adds to our knowledge about TE evolution but will also help
      in the annotation of repeats on Dipteran whole genome sequences.

PMID- 23552493
TI  - Molecular dynamics simulations for the motion of evaporative droplets driven by
      thermal gradients along nanochannels.
AB  - For a one-component fluid on a solid substrate, a thermal singularity may occur
      at the contact line where the liquid-vapor interface intersects the solid
      surface. Physically, the liquid-vapor interface is almost isothermal at the
      liquid-vapor coexistence temperature in one-component fluids while the solid
      surface is almost isothermal for solids of high thermal conductivity. Therefore,
      a temperature discontinuity is formed if the two isothermal interfaces are of
      different temperatures and intersect at the contact line. This leads to the so
      called thermal singularity. The localized hydrodynamics involving
      evaporation/condensation near the contact line leads to a contact angle depending
      on the underlying substrate temperature. This dependence has been shown to lead
      to the motion of liquid droplets on solid substrates with thermal gradients (Xu
      and Qian 2012 Phys. Rev. E 85 061603). In the present work, we carry out
      molecular dynamics (MD) simulations as numerical experiments to further confirm
      the predictions made from our previous continuum hydrodynamic modeling and
      simulations, which are actually semi-quantitatively accurate down to the small
      length scales in the problem. Using MD simulations, we investigate the motion of
      evaporative droplets in one-component Lennard-Jones fluids confined in
      nanochannels with thermal gradients. The droplet is found to migrate in the
      direction of decreasing temperature of solid walls, with a migration velocity
      linearly proportional to the temperature gradient. This agrees with the
      prediction of our continuum model. We then measure the effect of droplet size on
      the droplet motion. It is found that the droplet mobility is inversely
      proportional to a dimensionless coefficient associated with the total rate of
      dissipation due to droplet movement. Our results show that this coefficient is of
      order unity and increases with the droplet size for the small droplets (~10 nm)
      simulated in the present work. These findings are in semi-quantitative agreement
      with the predictions of our continuum model. Finally, we measure the effect of
      liquid-vapor coexistence temperature on the droplet motion. Through a theoretical
      analysis on the size of the thermal singularity, it can be shown that the droplet
      mobility decreases with decreasing coexistence temperature. This is observed in
      our MD simulations.

PMID- 23552488
TI  - Genetic dissection of drug resistance in trypanosomes.
AB  - The trypanosomes cause two neglected tropical diseases, Chagas disease in the
      Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a
      raft of molecular tools have been developed enabling the genetic dissection of
      many aspects of trypanosome biology, including the mechanisms underlying
      resistance to some of the current clinical and veterinary drugs. This has led to
      the identification and characterization of key resistance determinants, including
      transporters for the anti-Trypanosoma brucei drugs, melarsoprol, pentamidine and
      eflornithine, and the activator of nifurtimox-benznidazole, the anti-Trypanosoma
      cruzi drugs. More recently, advances in sequencing technology, combined with the
      development of RNA interference libraries in the clinically relevant bloodstream
      form of T. brucei have led to an exponential increase in the number of proteins
      known to interact either directly or indirectly with the anti-trypanosomal drugs.
      In this review, we discuss these findings and the technological developments that
      are set to further revolutionise our understanding of drug-trypanosome
      interactions. The new knowledge gained should inform the development of novel
      interventions against the devastating diseases caused by these parasites.

PMID- 23552494
TI  - Phenotypic and molecular differences between rats selectively bred to voluntarily
      run high vs. low nightly distances.
AB  - The purpose of the present study was to partially phenotype male and female rats
      from generations 8-10 (G8-G10) that had been selectively bred to possess low
      (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with
      wheels, 34-day-old G8 male and female LVRs ran shorter distances (P < 0.001),
      spent less time running (P < 0.001), and ran slower (P < 0.001) than their G8
      male and female HVR counterparts, respectively. HVR and LVR lines consumed
      similar amounts of standard chow with or without wheels. No inherent difference
      existed in PGC-1alpha mRNA in the plantaris and soleus muscles of LVR and HVR
      nonrunners, although G8 LVR rats inherently possessed less NADH-positive
      superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass
      tended to be greater in both sexes of G9-G10 LVR nonrunners vs. G9-G10 HVR
      nonrunners (P = 0.06), body fat percentage was similar between lines. G9-G10 HVRs
      had fat mass loss after 6 days of running compared with their prerunning values,
      while LVR did not lose or gain fat mass during the 6-day voluntary running
      period. RNA deep sequencing efforts in the nucleus accumbens showed only eight
      transcripts to be >1.5-fold differentially expressed between lines in HVR and LVR
      nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to
      potential differences in dopaminergic signaling between lines. This unique animal
      model provides further evidence as to how exercise may be mechanistically
      regulated.

PMID- 23552495
TI  - Protective role of testosterone in ischemia-reperfusion-induced acute kidney
      injury.
AB  - Men are at greater risk for renal injury and dysfunction after acute ischemia
      reperfusion (I/R) than are women. Studies in animals suggest that the reason for
      the sex difference in renal injury and dysfunction after I/R is the protective
      effect of estrogens in females. However, a reduction in testosterone in men is
      thought to play an important role in mediating cardiovascular and renal disease,
      in general. In the present study, we tested the hypothesis that I/R of the kidney
      reduces serum testosterone, and that contributes to renal dysfunction and injury.
      Male rats that were subjected to renal ischemia of 40 min followed by reperfusion
      had a 90% reduction in serum testosterone by 3 h after reperfusion that remained
      at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the
      increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24
      h, prevented the reduction in outer medullary blood flow, and attenuated the
      increase in intrarenal TNF-alpha and the decrease in intrarenal VEGF at 48 h.
      Castration of males caused greater increases in plasma creatinine and KIM-1 at 24
      h than in intact males with renal I/R, and treatment with anastrozole, an
      aromatase inhibitor, plus testosterone almost normalized plasma creatinine and
      KIM-1 in rats with renal I/R. These data show that renal I/R is associated with
      sustained reductions in testosterone, that testosterone repletion protects the
      kidney, whereas castration promotes renal dysfunction and injury, and that the
      testosterone-mediated protection is not conferred by conversion to estradiol.

PMID- 23552496
TI  - Therapeutic ketosis with ketone ester delays central nervous system oxygen
      toxicity seizures in rats.
AB  - Central nervous system oxygen toxicity (CNS-OT) seizures occur with little or no
      warning, and no effective mitigation strategy has been identified. Ketogenic
      diets (KD) elevate blood ketones and have successfully treated drug-resistant
      epilepsy. We hypothesized that a ketone ester given orally as R,S-1,3-butanediol
      acetoacetate diester (BD-AcAc(2)) would delay CNS-OT seizures in rats breathing
      hyperbaric oxygen (HBO(2)). Adult male rats (n = 60) were implanted with
      radiotelemetry units to measure electroencephalogram (EEG). One week postsurgery,
      rats were administered a single oral dose of BD-AcAc(2), 1,3-butanediol (BD), or
      water 30 min before being placed into a hyperbaric chamber and pressurized to 5
      atmospheres absolute (ATA) O2. Latency to seizure (LS) was measured from the time
      maximum pressure was reached until the onset of increased EEG activity and tonic
      clonic contractions. Blood was drawn at room pressure from an arterial catheter
      in an additional 18 animals that were administered the same compounds, and levels
      of glucose, pH, Po(2), Pco(2), beta-hydroxybutyrate (BHB), acetoacetate (AcAc),
      and acetone were analyzed. BD-AcAc(2) caused a rapid (30 min) and sustained (>4
      h) elevation of BHB (>3 mM) and AcAc (>3 mM), which exceeded values reported with
      a KD or starvation. BD-AcAc(2) increased LS by 574 +/- 116% compared with control
      (water) and was due to the effect of AcAc and acetone but not BHB. BD produced
      ketosis in rats by elevating BHB (>5 mM), but AcAc and acetone remained low or
      undetectable. BD did not increase LS. In conclusion, acute oral administration of
      BD-AcAc(2) produced sustained ketosis and significantly delayed CNS-OT seizures
      by elevating AcAc and acetone.

PMID- 23552497
TI  - Plasticity of cardiovascular function in snapping turtle embryos (Chelydra
      serpentina): chronic hypoxia alters autonomic regulation and gene expression.
AB  - Reptile embryos tolerate large decreases in the concentration of ambient oxygen.
      However, we do not fully understand the mechanisms that underlie embryonic
      cardiovascular short- or long-term responses to hypoxia in most species. We
      therefore measured cardiac growth and function in snapping turtle embryos
      incubated under normoxic (N21; 21% O2) or chronic hypoxic conditions (H10; 10%
      O2). We determined heart rate (fH) and mean arterial pressure (Pm) in acute
      normoxic (21% O2) and acute hypoxic (10% O2) conditions, as well as embryonic
      responses to cholinergic, adrenergic, and ganglionic pharmacological blockade.
      Compared with N21 embryos, chronic H10 embryos had smaller bodies and relatively
      larger hearts and were hypotensive, tachycardic, and following autonomic neural
      blockade showed reduced intrinsic fH at 90% of incubation. Unlike other reptile
      embryos, cholinergic and ganglionic receptor blockade both increased fH. beta
      Adrenergic receptor blockade with propranolol decreased fH, and alpha-adrenergic
      blockade with phentolamine decreased Pm. We also measured cardiac mRNA
      expression. Cholinergic tone was reduced in H10 embryos, but cholinergic receptor
      (Chrm2) mRNA levels were unchanged. However, expression of adrenergic receptor
      mRNA (Adrb1, Adra1a, Adra2c) and growth factor mRNA (Igf1, Igf2, Igf2r, Pdgfb)
      was lowered in H10 embryos. Hypoxia altered the balance between cholinergic
      receptors, alpha-adrenoreceptor and beta-adrenoreceptor function, which was
      reflected in altered intrinsic fH and adrenergic receptor mRNA levels. This is
      the first study to link gene expression with morphological and cardioregulatory
      plasticity in a developing reptile embryo.

PMID- 23552498
TI  - Detecting physiological systems with laser speckle perfusion imaging of the renal
      cortex.
AB  - Laser speckle perfusion imaging (LSPI) has become an increasingly popular
      technique for monitoring vascular perfusion over a tissue surface. However, few
      studies have utilized the full range of spatial and temporal information
      generated by LSPI to monitor spatial properties of physiologically relevant
      dynamics. In this study, we extend the use of LSPI to analyze renal perfusion
      dynamics over a spatial surface of ~5 * 7 mm of renal cortex. We identify
      frequencies related to five physiological systems that induce temporal changes in
      renal vascular perfusion (cardiac flow pulse, respiratory-induced oscillations,
      baroreflex components, the myogenic response, and tubuloglomerular feedback)
      across the imaged surface and compare the results with those obtained from renal
      blood flow measurements. We find that dynamics supplied from global sources
      (cardiac, respiration, and baroreflex) present with the same frequency at all
      locations across the imaged surface, but the local renal autoregulation dynamics
      can be heterogeneous in their distribution across the surface. Moreover, transfer
      function analysis with forced blood pressure as the input yields the same
      information with laser speckle imaging or renal blood flow as the output during
      control, intrarenal infusion of N(omega)-nitro-L-arginine methyl ester to enhance
      renal autoregulation, and intrarenal infusion of the rho-kinase inhibitor Y-27632
      to inhibit vasomotion. We conclude that LSPI measurements can be used to analyze
      local as well as global renal perfusion dynamics and to study the properties of
      physiological systems across the renal cortex.

PMID- 23552500
TI  - Eye movements during natural actions in patients with schizophrenia.
AB  - BACKGROUND: Visual scanning and planning of actions are reported to be abnormal
      in patients with schizophrenia. Most studies that monitored eye movements in
      these patients were performed under free-viewing conditions and used 2-
      dimensional images. However, images differ from the natural world in several
      ways, including task demands and the dimensionality of the display. Our study was
      designed to assess whether abnormalities in visual exploration in patients with
      schizophrenia generalize to active-viewing tasks in realistic conditions of
      viewing and to examine whether disturbances in action sequencing in these
      patients are reflected in their visual scanning patterns while executing natural
      tasks. METHODS: We monitored visual scan paths in patients with schizophrenia and
      healthy controls. Participants performed several tasks in which they were asked
      to look at a realistic scene on a table (free-viewing) and perform 2 active
      viewing tasks: a familiar task (sandwich-making) and an unfamiliar task (model
      building). The scenes contained both task-relevant and task-irrelevant objects.
      RESULTS: We included 15 patients and 15 controls in our analysis. Patients
      exhibited abnormalities in the free-viewing condition. Their patterns of
      exploration were similar to those of controls in the familiar task, but they
      showed scanning differences in the unfamiliar task. Patients were also slower
      than controls to accomplish both tasks. LIMITATIONS: Patients with schizophrenia
      were taking antipsychotic medications, so the presence of medication effects
      cannot be excluded. CONCLUSION: People with schizophrenia present a basic
      psychomotor slowing and seem to establish a less efficient planning strategy in
      the case of more complex and unfamiliar tasks.

PMID- 23552499
TI  - Antioxidant-based therapies for angiotensin II-associated cardiovascular
      diseases.
AB  - Cardiovascular diseases, including hypertension and heart failure, are associated
      with activation of the renin-angiotensin system (RAS) and increased circulating
      and tissue levels of ANG II, a primary effector peptide of the RAS. Through its
      actions on various cell types and organ systems, ANG II contributes to the
      pathogenesis of cardiovascular diseases by inducing cardiac and vascular
      hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys,
      sympathoexcitation, and activation of the immune system. Cardiovascular research
      over the past 15-20 years has clearly implicated an important role for elevated
      levels of reactive oxygen species (ROS) in mediating these pathophysiological
      actions of ANG II. As such, the use of antioxidants, to reduce the elevated
      levels of ROS, as potential therapies for various ANG II-associated
      cardiovascular diseases has been intensely investigated. Although some
      antioxidant-based therapies have shown therapeutic impact in animal models of
      cardiovascular disease and in human patients, others have failed. In this review,
      we discuss the benefits and limitations of recent strategies, including gene
      therapy, dietary sources, low-molecular-weight free radical scavengers,
      polyethylene glycol conjugation, and nanomedicine-based technologies, which are
      designed to deliver antioxidants for the improved treatment of cardiovascular
      diseases. Although much work has been completed, additional research focusing on
      developing specific antioxidant molecules or proteins and identifying the ideal
      in vivo delivery system for such antioxidants is necessary before the use of
      antioxidant-based therapies for cardiovascular diseases become a clinical
      reality.

PMID- 23552502
TI  - Hydrogen and carbon monoxide generation from laser-induced graphitized
      nanodiamonds in water.
AB  - Nanodiamonds (ND) were found to generate hydrogen (H2) and carbon monoxide (CO)
      from water at a remarkable rate under pulsed laser (532 nm) irradiation. The
      transformation of diamond structure into graphitic layers takes place to form an
      onion-like carbon structure. The CO generation suggests the oxidative degradation
      reaction of graphitic layers, C + H2O -> CO + 2H(+) + 2e(-), which produced a
      unique laser-induced reaction: C + H2O -> CO + H2. Au, Pt, Pd, Ag, and Cu
      nanoparticles on the ND enhance both gas evolution rates (~2 times for Au) and
      graphitization and, specifically, Au was found to be the most efficient amongst
      other nanoparticles. The enhancement effect was ascribed to effective charge
      separation between the metal nanoparticles and ND. The Au-ND hybrid on the
      reduced graphene oxide produced consistently a greater photocurrent than the ND
      upon visible light irradiation.

PMID- 23552501
TI  - Reversal deficits in individuals with psychopathy in explicit but not implicit
      learning conditions.
AB  - BACKGROUND: Psychopathy is a severe personality disorder that has been linked to
      impaired behavioural adaptation during reinforcement learning. Recent
      electrophysiological studies have suggested that psychopathy is related to
      impairments in intentionally using information relevant for adapting behaviour,
      whereas these impairments remain absent for behaviour relying on automatic use of
      information. We sought to investigate whether previously found impairments in
      response reversal in individuals with psychopathy also follow this dichotomy. We
      expected response reversal to be intact when the automatic use of information was
      facilitated. In contrast, we expected impaired response reversal when intentional
      use of information was required. METHODS: We included offenders with psychopathy
      and matched healthy controls in 2 experiments with a probabilistic cued go/no-go
      reaction time task. The task implicated the learning and reversal of 2 predictive
      contingencies. In experiment 1, participants were not informed about the
      inclusion of a learning component, thus making cue-dependent learning
      automatic/incidental. In experiment 2, the instructions required participants to
      actively monitor and learn predictive relationships, giving learning a
      controlled/intentional nature. RESULTS: While there were no significant group
      differences in acquisition learning in either experiment, the results revealed
      impaired response reversal in offenders with psychopathy when controlled learning
      was facilitated. Interestingly, this impairment was absent when automatic
      learning was predominant. LIMITATIONS: Possible limitations are the use of a
      nonforensic control group and of self-report measures for drug use. CONCLUSION:
      Response reversal deficits in individuals with psychopathy are modulated by the
      context provided by the instructions, according to the distinction between
      automatic and controlled processing in these individuals.

PMID- 23552503
TI  - Nutrient intake and dietary patterns of relevance to dental health of 12-year-old
      Libyan children.
AB  - OBJECTIVE: There are few data on the dietary intake of children in Libya, and
      none on free sugars intake. The present study aimed to report the intake of
      macronutrients and eating habits of relevance to dental health in a group of
      Libyan schoolchildren and to investigate any gender differences for these
      variables. DESIGN: Dietary information was obtained from a randomly selected
      sample using an estimated 3 d food diary. Dietary data were coded using food
      composition tables and entered into a Microsoft(r) Access database. Intakes of
      energy, macronutrients, sugars and the amount of acidic items consumed were
      determined using purpose-written programs. SETTING: Benghazi, Libya. SUBJECTS:
      Schoolchildren aged 12 years. RESULTS: One hundred and eighty children (ninety
      two boys and eighty-eight girls) completed the study. Their mean age was 12.3 (sd
      0.29) years. The average daily energy intake was 7.01 (sd 1.54) MJ/d. The
      percentage contributions to energy intake from protein, fat and carbohydrate were
      16 %, 30 % and 54 %, respectively. Total sugars contributed 20.4 % of the daily
      energy intake, and free sugars 12.6 %. The median daily intake of acidic items
      was 203 g/d, and of acidic drinks was 146 g/d. There were no statistically
      significant differences in nutrient intakes between genders. Intake of acidic
      items was higher in girls (P < 0.001). CONCLUSIONS: The contribution to energy
      intake from macronutrients was in accordance with global nutrition guidelines.
      The acidic drinks intake was low compared with other populations, while free
      sugars intake was above the recommended threshold of 10 % of energy intake.

PMID- 23552505
TI  - Access to medical-assisted reproduction and pgd in Italian law: a deadly blow to
      an illiberal statute? commentary to the European Court on Human Rights's decision
      Costa and Pavan v Italy (ECtHR, 28 August 2012, App. 54270/2010).
AB  - This article provides an account of the European Court on Human Rights' Second
      Section decision in the case Costa and Pavan v Italy. The judgment found that the
      Italian Statute on Assisted Reproduction (Law 40/2004), and particularly its
      prohibition to use in vitro fertilisation and pre-implantation genetic diagnosis
      (PGD) to prevent the birth of children affected by genetically transmissible
      conditions, breached Article 8 of the European Convention on Human Rights (ECHR).
      In fact, the statute in question permits only infertile people to access
      medically assisted reproduction techniques and forbids PGD and embryo selection.
      The Court regarded that the rationale of these prohibitions-identified by the
      Italian Government with the need to prevent eugenic practices as well as to
      protect the health of the unborn and of the woman-was at odds with the fact that
      Italian law allows pre-natal screening and therapeutic abortions in case foetal
      abnormalities are diagnosed. In order to clarify the decision's significance, the
      paper goes on to analyse the rationale of Law 40/2004 in the Italian legal and
      political context. Emphasis is placed on the fact that this statute is extremely
      controversial at domestic level, because many of its provisions-including those
      considered by the Strasbourg Court-are inherently contradictory and contrast with
      the settled constitutional principles on abortion, as many domestic authorities
      highlighted. In this context, should the commented decision be confirmed by the
      Grand Chamber, it may provide a basis to bring consistency back to the Italian
      regulation of assisted reproduction. Finally, the paper considers the appeal
      lodged by the Italian Government to the Grand Chamber, and in particular the
      contention that the European Court had failed to respect Italy's margin of
      appreciation. In this regard, it is argued that, under Law 40/2004, individuals
      face illogical and discriminatory restrictions to their right to private and
      family life and that therefore, even if an outright violation of Article 8 ECHR
      could not be found, there appears to be at least a breach of Article 8 in
      conjunction with Article 14 ECHR. 

PMID- 23552506
TI  - It's not just the patient.

PMID- 23552507
TI  - Early enhanced external counter pulsation improves neurological recovery after
      the return of spontaneous circulation in a mongrel dog cardiac arrest model*.
AB  - OBJECTIVES: The aim of this study was to investigate whether early enhanced
      external counter pulsation therapy after cardiopulmonary resuscitation improved
      neurological outcome in a mongrel dog cardiac arrest model. DESIGN: Randomized,
      animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Twenty-four
      healthy male adult dogs (12-14 kg). INTERVENTIONS: After minutes of untreated
      ventricular fibrillation followed by 2 minutes of cardiopulmonary resuscitation,
      the dogs were randomized to receive 4 hours of enhanced external counter
      pulsation therapy, to receive 4 hours of hypertension with over 140 mm Hg or to
      be a control. MEASUREMENTS: Blood pressure and left ventricular ejection fraction
      were recorded. Cerebral flow was assessed using magnetic resonance imaging.
      Arterial blood gases and endothelium-derived vasoactive substances were assessed
      before cardiac arrest and 4 hours after the return of spontaneous circulation.
      Neurological outcome was assessed by the neurologic deficit score and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS:
      Enhanced external counter pulsation significantly improved the left ventricular
      ejection fraction and increased common carotid artery blood flow and shear
      stress. Enhanced external counter pulsation increased both relative cerebral
      blood volume (RCBV, p = 0.043) and relative cerebral blood flow (RCBF, p = 0.012)
      in animals 4 hours after return of spontaneous circulation. Enhanced external
      counter pulsation therapy promoted the production of nitric oxide and tissue
      plasminogen activator and decreased the release of endothelin-1 (p = 0.013) after
      return of spontaneous circulation. Treatment with norepinephrine in the high mean
      artery pressure also increased common carotid artery blood flow and shear stress.
      However, no effects on the left ventricular ejection fraction, the production of
      nitric oxide and tissue plasminogen activator, or the release of endothelin-1
      were found. The neurologic deficit scores of the animals were significantly lower
      at 24, 48, 72, and 96 hours in the enhanced external counter pulsation group, as
      well as at 24, 72, and 96 hours compared with animals in the control group after
      return of spontaneous circulation. Fewer apoptotic neurons were observed in the
      animals in the enhanced external counter pulsation group compared with the
      animals in the control and hypertension groups. CONCLUSIONS: These data indicated
      that the treatment of early enhanced external counter pulsation improved
      neurological outcome by both increasing cerebral blood flow and improving the
      recovery of microcirculation after return of spontaneous circulation. The
      treatment of early enhanced external counter pulsation can be a good option for
      protecting the brain after return of spontaneous circulation.

PMID- 23552508
TI  - Impact of advanced healthcare directives on treatment decisions by physicians in
      patients with acute stroke.
AB  - BACKGROUND: The implementation of advanced healthcare directives, prepared by
      almost half of the adult population in United States remains relatively under
      studied. We determined the impact of advanced healthcare directives on treatment
      decisions by multiple physicians in stroke patients. METHODS: A deidentified
      summary of clinical and radiological records of 28 patients with stroke was given
      to six stroke physicians who were not involved in the care of the patients. Each
      physician independently rated 28 treatment decisions per patient in the presence
      or absence of advanced healthcare directives 1 month apart to allow memory
      washout. The percentage agreement to treat/intervene per patient and proportion
      of treatment withheld as a group were estimated for each of the 28 treatment
      decision items. We also determined the interobserver reliability between the two
      raters (attorneys) in interpretation of six items characterizing the adequacy of
      documentation within the 28 advanced healthcare directives. RESULTS: The
      percentage agreement among physician raters for treatment decisions in 28 stroke
      patients was highest for treatment of hyperpyrexia (100%, 100%) and lowest for
      ICU monitoring duration based on family-physician considerations outside of
      accepted criteria within institution (68%, 69%) in presence and absence of
      advanced healthcare directives. The physician rater agreement in choosing "yes"
      was highest for "routine-complexity" treatment decisions and lowest for "moderate
      complexity" treatment decisions. The choice of withholding treatment in "routine
      complexity," "moderate-complexity," or "high-complexity" treatment decisions was
      remarkably similar among raters in presence or absence of advanced healthcare
      directives. The only treatment decision that showed an impact of advanced
      healthcare directives was ICU monitoring withheld in 32% of treatment decisions
      in presence of directives (compared with 8% in the absence of directives). IV
      medication and defibrillation for cardiac arrest was withheld in 29% (compared
      with 19%) of the treatment decisions in the presence of advanced healthcare
      directives. The two attorney raters found the description of acceptable outcome
      inadequate in 14 and 21 of 28 advanced healthcare directives reviewed,
      respectively. The overall mean kappa for agreement regarding adequacy of
      documentation was modest (43%) for "does the advanced healthcare directive
      specify which treatments the patient would choose, or refuse to receive if they
      were diagnosed with an acute, terminal condition?" and lowest (3%) for
      "description of acceptable outcome." CONCLUSIONS: We did not find any prominent
      differences in most "routine-complexity," "moderate-complexity," or "high
      complexity" treatment decisions in patient management in the presence of advanced
      healthcare directives. Presence of advanced healthcare directives also did not
      reduce the prominent variance among physicians in treatment decisions.

PMID- 23552510
TI  - Physicians' decision-making roles for an acutely unstable critically and
      terminally ill patient.
AB  - OBJECTIVES: There is substantial variation in use of life sustaining technologies
      in patients near the end of life but little is known about variation in
      physicians' initial ICU admission and intubation decision making processes. Our
      objective is to describe variation in hospital-based physicians' communication
      behaviors and decision-making roles for ICU admission and intubation decisions
      for an acutely unstable critically and terminally ill patient. DESIGN: We
      conducted a secondary analysis of transcribed simulation encounters from a multi
      center observational study of physician decision making. The simulation depicted
      a 78-year-old man with metastatic gastric cancer and life threatening hypoxia. He
      has stable underlying preferences against ICU admission and intubation that he or
      his wife will report if asked. We coded encounters for communication behaviors
      (providing medical information, eliciting preferences/values, engaging the
      patient/surrogate in deliberation, and providing treatment recommendations) and
      used a previously-developed framework to classify subject physicians into four 
      mutually-exclusive decision-making roles: informative (providing medical
      information only), facilitative (information + eliciting preferences/values +
      guiding surrogate to apply preferences/values), collaborative (information +
      eliciting + guiding + making a recommendation) and directive (making an
      independent treatment decision). SETTING: Simulation centers at 3 US academic
      medical centers. SUBJECTS: Twenty-four emergency physicians, 37 hospitalists, and
      37 intensivists. MEASUREMENTS AND MAIN RESULTS: Subject physicians average 12.4
      years (SD 9.0) since graduation from medical school. Of 98 physicians (39%), 38
      physicians sent the patient to the ICU, and 9 of 98 (9%) ultimately decided to
      intubate. Most (93 of 98 [95%]) provided at least some medical information, but
      few explained the short-term prognosis with (26 of 98 [27%]) or without
      intubation (37 of 98 [38%]). Many (80 of 98 [82%]) elicited the patient's
      intubation preferences, but few (35 of 98 [36%]) explored the patient's broader
      values. Based on coded behaviors, we categorized 1 of 98 (1%) as informative, 48
      of 98 (49%) as facilitative, 36 of 98 (37%) as collaborative, and 12 of 98 (12%)
      as directive; 1 of 98 (1%) could not be placed into a category. No observed
      physician characteristics predicted decision-making role. CONCLUSIONS: The
      majority of the physicians played a facilitative or collaborative role, although
      a greater proportion assumed a directive role in this time-pressured scenario
      than has been documented in nontime-pressured ICU family meetings, suggesting
      that physicians' roles may be context dependent.

PMID- 23552509
TI  - Early oxygenation and ventilation measurements after pediatric cardiac arrest:
      lack of association with outcome.
AB  - OBJECTIVES: To explore oxygenation and ventilation status early after cardiac
      arrest in infants and children. We hypothesize that hyperoxia is common and
      associated with worse outcome after pediatric cardiac arrest. DESIGN:
      Retrospective cohort study. SETTING: Fifteen hospitals within the Pediatric
      Emergency Care Applied Research Network. PATIENTS: Children who suffered a
      cardiac arrest event and survived for at least 6 hours after return of
      circulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of 195
      events revealed that abnormalities in oxygenation and ventilation are common
      during the initial 6 hours after pediatric cardiac arrest. Hyperoxia was
      frequent, affecting 54% of patients. Normoxia was documented in 34% and hypoxia
      in 22% of patients. These percentages account for a 10% overlap of patients who
      had both hyperoxia and hypoxia. Ventilation status was more evenly distributed
      with hyperventilation observed in 38%, normoventilation in 29%, and
      hypoventilation in 46%, with a 13% overlap of patients who had both
      hyperventilation and hypoventilation. Derangements in both oxygenation and
      ventilation were common early after cardiac arrest such that both normoxia and
      normocarbia were documented in only 25 patients (13%). Neither oxygenation nor
      ventilation status was associated with outcome. After controlling for potential
      confounders, arrest location and rhythm were significantly associated with worse
      outcome; however, hyperoxia was not (odds ratio for good outcome, 1.02 [0.46,
      2.84]; p = 0.96). CONCLUSIONS: Despite recent resuscitation guidelines that
      advocate maintenance of normoxia and normoventilation after pediatric cardiac
      arrest, this is uncommonly achieved in practice. Although we did not demonstrate
      an association between hyperoxia and worse outcome, the small proportion of
      patients kept within normal ranges limited our power. Preclinical data suggesting
      potential harm with hyperoxia remain compelling, and further investigation,
      including prospective, large studies involving robust recording of physiological
      derangements, is necessary to further advance our understanding of this important
      topic.

PMID- 23552511
TI  - The pea aphid uses a version of the terminal system during oviparous, but not
      viviparous, development.
AB  - BACKGROUND: In most species of aphid, female nymphs develop into either sexual or
      asexual adults depending on the length of the photoperiod to which their mothers
      were exposed. The progeny of these sexual and asexual females, in turn, develop
      in dramatically different ways. The fertilized oocytes of sexual females begin
      embryogenesis after being deposited on leaves (oviparous development) while the
      oocytes of asexual females complete embryogenesis within the mother (viviparous
      development). Compared with oviparous development, viviparous development
      involves a smaller transient oocyte surrounded by fewer somatic epithelial cells
      and a smaller early embryo that comprises fewer cells. To investigate whether
      patterning mechanisms differ between the earliest stages of the oviparous and
      viviparous modes of pea aphid development, we examined the expression of pea
      aphid orthologs of genes known to specify embryonic termini in other insects.
      RESULTS: Here we show that pea aphid oviparous ovaries express torso-like in
      somatic posterior follicle cells and activate ERK MAP kinase at the posterior of
      the oocyte. In addition to suggesting that some posterior features of the
      terminal system are evolutionarily conserved, our detection of activated ERK in
      the oocyte, rather than in the embryo, suggests that pea aphids may transduce the
      terminal signal using a mechanism distinct from the one used in Drosophila. In
      contrast with oviparous development, the pea aphid version of the terminal system
      does not appear to be used during viviparous development, since we did not detect
      expression of torso-like in the somatic epithelial cells that surround either the
      oocyte or the blastoderm embryo and we did not observe restricted activated ERK
      in the oocyte. CONCLUSIONS: We suggest that while oviparous oocytes and embryos
      may specify posterior fate through an aphid terminal system, viviparous oocytes
      and embryos employ a different mechanism, perhaps one that does not rely on an
      interaction between the oocyte and surrounding somatic cells. Together, these
      observations provide a striking example of a difference in the fundamental events
      of early development that is both environmentally induced and encoded by the same
      genome.

PMID- 23552515
TI  - Association among blood pressure control in elderly patients with hypertension,
      left atrial structure and function and new-onset atrial fibrillation: a
      prospective 2-year study in 234 patients.
AB  - We assessed the hypothesis that blood pressure (BP)-lowering therapy has a
      beneficial effect on left atrial (LA) structure and function and may decrease the
      incidence of new-onset atrial fibrillation (AF) in elderly patients with
      hypertension (HTN). We divided 234 subjects >=65 years old into four groups based
      on mean office BP achieved: a normotensive group (n=71), a HTN group with good BP
      control (n=72), a HTN group with poor BP control (n=41) and a HTN group with
      moderate BP control (n=50). LA volume, emptying function (EF), strain and strain
      rate (SR) were measured by speckle tracking echocardiography. LA volume, EF,
      strain and SR in the HTN group with good BP control were better preserved than
      those parameters in the HTN group with poor BP control. The incidence of new
      onset AF during 2 years was significantly higher in the HTN group with poor BP
      control (hazard ratio: 7.015; 95% confidence interval: 2.433-20.22; P<0.001). In
      multivariate Cox regression analysis that included the difference in
      echocardiographic parameters between baseline and follow-up, both age and being
      in the HTN group with poor BP control were independent predictors of new-onset
      AF. In multivariate Cox regression analysis that included only parameters at
      baseline, ratio of the peak early transmitral flow velocity (E) to the peak early
      myocardial tissue velocity (E/e') was an independent predictor of new-onset AF.
      The incidence of new-onset AF depended on the long-term level of BP control
      rather than short-term changes in LA structure and function. Poor BP control
      increased the risk of new-onset AF in elderly patients with HTN.

PMID- 23552514
TI  - Chinese herbal formulas for treating hypertension in traditional Chinese
      medicine: perspective of modern science.
AB  - Hypertension, which directly threatens quality of life, is a major contributor to
      cardiovascular and cerebrovascular events. Over the past two decades, domestic
      and foreign scholars have agreed upon various standards in the treatment of
      hypertension, and considerable progress has been made in the field of
      antihypertensive drugs. Oral antihypertensive drugs represent a milestone in
      hypertension therapy. However, the blood pressure standard for patients with
      hypertension is far from satisfactory. The study of Chinese herbal formulas for
      treating hypertension has received much research attention. These studies seek to
      integrate traditional and Western medicine in China. Currently, Chinese herbal
      formulas are known to have an outstanding advantage with regard to bodily
      regulation. Research shows that Chinese medicine has many protective mechanisms.
      This paper addresses the process of the antihypertensive mechanisms in Chinese
      herbal formulas for treating hypertension. These mechanisms are to be discussed
      in future research. 

PMID- 23552512
TI  - New approaches for understanding mechanisms of drug resistance in schistosomes.
AB  - Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected
      tropical disease that affects hundreds of millions worldwide. Treatment and
      control of schistosomiasis relies almost entirely on the single drug praziquantel
      (PZQ), making the prospect of emerging drug resistance particularly worrisome.
      This review will survey reports of PZQ (and other drug) resistance in
      schistosomes and other platyhelminths, and explore mechanisms by which drug
      resistance might develop. Newer genomic and post-genomic strategies that offer
      the promise of better understanding of how drug resistance might arise in these
      organisms will be discussed. These approaches could also lead to insights into
      the mode of action of these drugs and potentially provide markers for monitoring
      the emergence of resistance.

PMID- 23552516
TI  - Significance of estimating the glomerular filtration rate for the management of
      hypertension in type 2 diabetes with microalbuminuria.
AB  - The Home Blood Pressure for Diabetic Nephropathy (HBP-DN) study is a prospective
      cohort study to determine the optimal home blood pressure (HBP) required to
      improve the prognosis of type 2 diabetic patients with microalbuminuria. The
      glomerular filtration rate (GFR) is heterogeneous in microalbuminuric diabetic
      patients. The first step of the HBP-DN study explored the significance of
      estimating GFR for the identification of patients for whom HBP measurement would
      be more helpful. The patients were divided into two groups based on their
      estimated GFR (eGFR): a low eGFR group (eGFR <60 ml min(-1) per 1.73 m(2), N=75)
      and a preserved eGFR group (eGFR ?60 ml min(-1) per 1.73 m(2), N=193). HBP,
      variability of HBP and a previous history of vascular complications were compared
      between the two groups. The number of antihypertensive drugs used for the
      patients and the s.d. of home systolic blood pressure (HSBP) in the low eGFR
      group were significantly higher than those in the preserved eGFR group. A
      stepwise multiple linear regression analysis also revealed that the low eGFR
      group was independently correlated with the s.d. of HSBP. A multiple logistic
      regression analysis revealed that a low eGFR was an independent risk factor for
      coronary heart disease and advanced retinopathy. Estimating the GFR is important
      to identify patients with elevated blood pressure variability, as well as those
      with a high risk of vascular complications. Measuring HBP would be more helpful
      for the effective and safe treatment of hypertension in patients with a low eGFR
      than in those with a preserved eGFR. 

PMID- 23552517
TI  - Modernization and hypertension: is the link changing?

PMID- 23552519
TI  - Welcome to oncogenesis.

PMID- 23552518
TI  - An identical, complex TP53 mutation arising independently in two unrelated
      families with diverse cancer profiles: the complexity of interpreting cancer risk
      in carriers.
AB  - Most inherited TP53 mutations have been identified in individuals with a family
      cancer predisposition syndrome, in which the activity of p53 mutants is severely
      reduced. However, germline p53 mutants in children with 'sporadic' adrenocortical
      or choroid plexus tumors exhibit a wide range of functional activity. Here, we
      demonstrate the occurrence of a complex germline TP53 mutation in two unrelated
      families with different cancer phenotypes, neither fulfilling the classic
      criteria for Li-Fraumeni syndrome. The TP53 mutation consists of a duplication of
      7 bp in exon 4, resulting in a frame shift and premature stop signal. Haplotype
      analysis indicated that the mutation arose independently in the two families.
      Analysis of the DNA secondary structure predicts the TP53 mutation occurred
      within a hairpin loop. Additional germline complex mutations occurring within the
      same region of exon 4 have been identified in the IARC database. Our findings
      suggest that certain TP53 regions are prone to intrinsic genetic alterations,
      possibly through defects in DNA replication or repair. Further, carriers of the
      same TP53 mutation can have diverse cancer profiles, illustrating the complexity
      of genetic counseling and risk prediction.

PMID- 23552520
TI  - Influence of the Ce-Zr promoter on Pd behaviour under dynamic CO/NO cycling
      conditions: a structural and chemical approach.
AB  - The behaviour of the Pd phase in three way catalysts (TWCs) having a Ce-Zr oxide
      as a promoter component has been examined under CO/NO cycling conditions. In
      order to extract information on the role of the noble metal and the metal
      promoter interface, two catalysts in, respectively, the presence or the absence
      of the promoter and having a similar Pd particle size were analyzed by a
      synchronous multitechnique approach using X-ray absorption (XAS) or high energy X
      ray diffraction (HXRD) in combination with diffuse reflectance Fourier transform
      infrared spectroscopy (DRIFTS) and mass spectrometry (MS). From a structural
      point of view it is shown that the promoter oxide strongly influences Pd
      behaviour, limiting morphological (size/shape) and structural (formation of
      carbide/oxide phases) modifications occurring under dynamic conditions in the
      absence of the promoter. Activity measurements show that these phenomena have
      important chemical consequences in terms of CO/NO pollutant metal coverage(s),
      the occurrence of NO and/or CO dissociation steps as well as the subsequent
      transformation of the pollutants into CO2 and N2.

PMID- 23552522
TI  - The natural estrogenic compound diarylheptanoid (D3): in vitro mechanisms of
      action and in vivo uterine responses via estrogen receptor alpha.
AB  - BACKGROUND: Diarylheptanoid (D3) isolated from the medicinal plant, Curcuma
      comosa, has estrogenic activity. OBJECTIVE: We aimed to elucidate the
      mechanism(s) of D3 action and compare it with that of 17beta-estradiol (E2) using
      both in vitro and in vivo uterine models. METHODS: We used human uterine
      (Ishikawa) cells to determine the estrogenic action of D3 on the activation and
      nuclear translocation of estrogen receptor alpha (ERalpha). In addition, we
      further characterized the uterine response to D3 treatment in vivo. RESULTS: D3
      activated an estrogen responsive element (ERE) luciferase reporter through
      ERalpha, and molecular modeling suggested that D3 could be accommodated in the
      ERalpha binding pocket. Using modified ERalpha to assay ligand-dependent nuclear
      translocation, we observed D3-dependent ERalpha interaction and translocation. In
      mouse uteri, early- and late-phase estrogen-regulated gene responses were
      increased in D3-treated ovariectomized wild-type animals, in a manner similar to
      that of E2; no response was seen in ERalpha knockout animals. We observed a
      divergence in estrogen responses after D3 treatment: D3 induced robust DNA
      synthesis in uterine epithelial cells, linked to an increase in cell-cycle
      related genes; however, no increase in uterine weight was observed 24 hr after
      treatment. D3 also affected uterine progesterone receptor expression patterns
      similar to E2. When D3 and E2 were administered together, we observed no additive
      or antagonistic effects of D3 on E2. Our findings suggest that D3 is a weak
      estrogenic agonist compound. CONCLUSION: D3 is a weakly acting phytoestrogen that
      mimics the mitogenic responses produced by E2 in an ERalpha-dependent manner, but
      it is unable to increase uterine weight or enhance or antagonize the effects of
      estrogen.

PMID- 23552523
TI  - Cyanide SERS as a platform for detection of volatile organic compounds and
      hazardous transition metal ions.
AB  - It is demonstrated herein that cyanide adsorbed on nanostructured Au is a very
      useful system for the detection of not only volatile organic compounds (VOCs) but
      also transition metal ions by means of surface-enhanced Raman scattering (SERS).
      This technique exploits the susceptibility of the CN stretching frequency of
      cyanide on Au to the variation of the surface potential of the Au nanostructures
      that occurs in response to the adsorption of VOCs onto these surfaces. It also
      exploits the susceptibility to the binding of transition metal cations to the
      pendant nitrogen atom, which reduces the anti-bonding character of the nitrogen
      lone pair of electrons. The CN stretching band was illustrated to undergo a blue
      shift by up to 20 cm(-1) in response to a typical biogenic VOC farnesol, whereas
      the band was red-shifted by 10 cm(-1) in response to the typical biogenic VOC (+)
      alpha-pinene. This method is considered to be highly sensitive given that the
      peak shift of 2 cm(-1) could be reproducibly measured even at a partial pressure
      of 1 Pa, corresponding to 76 ppm of farnesol. The CN stretching band was also
      demonstrated to undergo a blue-shift by up to 60-64 cm(-1) in the presence of
      trivalent cations such as Fe(3+) and Cr(3+), whereas the band was blue-shifted by
      26-35 cm(-1) in the presence of divalent metal ions such as Mn(2+) and Fe(2+).
      The present SERS method is regarded as very promising because transition metal
      ions were detectable at concentration levels as low as 1 fM.

PMID- 23552528
TI  - Introducing Misha Rosenbach, MD, section editor for JAMA Dermatology patient
      page.

PMID- 23552526
TI  - Aneurysmal subarachnoid hemorrhage: follow the guidelines.

PMID- 23552529
TI  - Annular dark-field transmission electron microscopy for low contrast materials.
AB  - Imaging soft matter by transmission electron microscopy (TEM) is anything but
      straightforward. Recently, interest has grown in developing alternative imaging
      modes that generate contrast without additional staining. Here, we present a dark
      field TEM technique based on the use of an annular objective aperture. Our
      experiments demonstrate an increase in both contrast and signal-to-noise ratio in
      comparison to conventional bright-field TEM. The proposed technique is easy to
      implement and offers an alternative imaging mode to investigate soft matter.

PMID- 23552524
TI  - Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti
      cancer effects in mouse lung metastasis melanoma.
AB  - BACKGROUND: The use of adenoviral vector for gene therapy is still an important
      strategy for advanced cancers, however, the lack of the requisite coxsackie
      adenovirus receptor in cancer cells and host immune response to adenovirus limit
      the application of adenoviral vector in vivo. METHOD: We designed the
      antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF)
      encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti
      tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis.
      RESULTS: We found that systemic administration of Ad-PEDF/liposome was well
      tolerated and resulted in marked suppression of tumor growth, and was more potent
      than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit
      murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with
      liposome, its distribution decreased in liver and increased in lung. The anti-Ad
      IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone.
      CONCLUSION: The present findings provide evidences of systematic administration
      of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice
      model, and show an encouraging therapeutic effect for further exploration and
      application of more complexes based on liposome-encapsulated adenovirus for more
      cancers.

PMID- 23552530
TI  - The clinical trial research: how random is random?

PMID- 23552531
TI  - Lipid profiles of non-diabetic healthy and ischaemic heart disease patients.
AB  - OBJECTIVE: To find any difference in the fasting lipid profile in patients with
      history of ischaemic heart disease (IHD) and established atherosclerotic plaques
      on angiography and in subjects with no known history of IHD. STUDY DESIGN:
      Observational, cross-sectional study. PLACE AND DURATION OF STUDY: Immunology
      Department of University of Health Sciences, Lahore, from January 2007 to January
      2009. METHODOLOGY: In this study, 200 male subjects, between 40 and 60 years of
      age were recruited. Serum cholesterol and triglycerides were determined by
      enzymatic CHOD-PAP and GPO-PAP calorimetric method, HDL-C by accelerator
      selective detergent method and LDL-C by direct homogeneous enzymatic method.
      Serum ox-LDL contents were determined by using quantitative sandwich enzyme
      immuno-assay kits. RESULTS: The total serum cholesterol, triglyceride and LDL-C
      levels were within the normal range in control and patient groups whereas HDL-C
      levels were significantly higher in the control group compared to the patient
      group (p = 0.001). A significant difference (p = 0.001) for HDL-C levels was
      observed between smokers and non-smokers. Serum ox-LDL levels were higher in
      patient group as compared to the control group but the difference was not
      statistically significant. CONCLUSION: The significantly lower HDL levels in
      patient group with normal cholesterol, LDL and triglyceride levels may suggest
      low HDL-C has a greater role in IHD. Raising plasma HDL-cholesterol through
      weight loss, healthy diet, increased physical activity and by proper
      pharmacotherapy is, therefore, a legitimate therapeutic target for the optimal
      prevention of CHD in native population.

PMID- 23552532
TI  - Frequency of precancerous lesions in endoscopic gastric biopsies in chronic
      gastritis.
AB  - OBJECTIVE: To determine the frequency of precancerous lesions in endoscopic
      gastric biopsies of patients with chronic gastritis. STUDY DESIGN: A case series.
      PLACE AND DURATION OF STUDY: Department of Histopathology, Liaquat National
      Hospital, Karachi, from July 2008 to January 2009. METHODOLOGY: Over 6 months,
      375 endoscopic gastric biopsies of patients with age group of 15-65 years having
      endoscopic chronic gastritis were included. From final biopsy report, basic
      information like patient demographics and presence of precancerous lesions i.e.
      activity (chronic active gastritis), atrophy (atrophic gastritis), intestinal
      metaplasia and dysplasia were recorded on proforma. Results were described as
      proportions and frequency. RESULTS: The frequency of precancerous lesions in
      endoscopic gastric biopsies of patients with chronic gastritis in Karachi was
      markedly high. Most common lesion was chronic active gastritis as depicted by
      activity (48.3%); dysplasia (1.3%) was the least common. Proportion of more
      aggressive precancerous lesions were markedly higher in older age group (> 40
      years). CONCLUSION: The precancerous lesions are frequent in endoscopic gastric
      biopsies of patients with chronic gastritis.

PMID- 23552533
TI  - Multi-resource peer assisted learning in postgraduate setting: a pilot study.
AB  - OBJECTIVE: To evaluate the satisfaction of participants and the effectiveness of
      an enhanced and relatively formal type of peer assisted learning (PAL) in
      postgraduate (PG) setting. STUDY DESIGN: An observational study. PLACE AND
      DURATION OF STUDY: Layton Rehmat Ullah Benevolent Trust, Eye Hospital, Sargodha
      between 2008 and 2009. METHODOLOGY: Participants were 6 medical officers and 2
      consultants. Resources and sessions were defined and the curriculum agreed
      through consensus between all peers. Thirty clinically relevant topics on
      diseases, techniques and practicals were selected for PAL sessions. A 26-item
      questionnaire was used to evaluate PAL on Likert-scale. It also included a free
      text question about one strength and one weakness of PAL. The participants
      consented to all aspects of multi-resource PAL and they completed a
      questionnaire, from which data was gathered and analysed to reveal the impact of
      course. RESULTS: As a peer group they were satisfied with the teamwork
      experience. Seven out of eight peers reported to have increased their motivation
      level. In addition, as a peer tutor all peers accepted that the course equipped
      them with teaching skills and that teaching skills should be learnt. Similarly,
      as a peer tutee, they believe that peer assistance in a multiresource format had
      a positive impact on their learning and their difficult issues were unravelled.
      Finally, facilitated small group teaching, discussion and summing-up helped the
      peers to comprehend a given clinical topic. CONCLUSION: A pilot multi-resource
      PAL was evaluated and the participants appraised the course favourably and
      recommended it to their colleagues. The interest and zeal shown by the
      participants suggests that further investigation through a larger, prospective
      study is warranted.

PMID- 23552534
TI  - Anterior cervical decompression and fusion with Caspar plate fixation.
AB  - OBJECTIVE: To evaluate the role of anterior cervical decompression and fixation
      with Caspar plating in cervical spine injury on neurological outcome. STUDY
      DESIGN: A case series. PLACE AND DURATION OF STUDY: Department of Neurosurgery,
      Jinnah Postgraduate Medical Centre, Karachi, from July 2008 to March 2011.
      METHODOLOGY: Thirty patients admitted with cervical spine injuries were inducted
      in the study. All cases were evaluated for their clinical features, level of
      injury and degree of neurological injury was assessed using Frankel grading. Pre
      and postoperative record with X-rays and MRI were maintained. Cervical traction
      was applied to patients with sub-luxation. All patients underwent anterior
      cervical decompression, fusion and Caspar plate fixation. The follow-up period
      was 6 months with clinical and radiological assessment. RESULTS: Among 30
      patients, 24 (80%) were males and 6 (20%) were females. Age ranged from 15 to 55
      years. Causes of injury were road traffic accident (n = 20), fall (n = 8) and
      assault (n = 2). Commonest mode of injury was road traffic accident (66.6%).
      Postoperative follow-up showed that pain and neurological deficit were improved
      in 21 patients. There was no improvement in 7 patients, one patient deteriorated
      and one expired. All patients developed pain at donor site. CONCLUSION: Anterior
      decompression, fusion and fixation with Caspar plate is an effective method with
      good neurological and radiological outcome. However, it is associated with pain
      at donor site.

PMID- 23552535
TI  - Retinal detachment in paediatric patients.
AB  - OBJECTIVE: To assess the causes of retinal detachment in children and the various
      operative procedures requiring vitreoretinal surgical intervention for the same.
      STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of
      Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, from January 2006 to May
      2009. METHODOLOGY: A total of 281 eyes of 258 patients, (aged 0-18 years) who
      underwent vitreo-retinal surgical intervention for retinal detachment were
      included. Surgical log was searched for the type of retinal detachment and its
      causes. Frequencies of various interventions done in these patients viz.
      vitrectomy, scleral buckle, use of tamponading agents, laser photocoagulation and
      cryotherapy were noted. Results were described as descriptive statistics.
      RESULTS: Myopia was the cause in 62 (22.1%) and trauma in 51 (18.1%) of the eyes.
      Total retinal detachment (RD) was treated in 94 (33.5%) eyes, sub total RD in 36
      (12.8%), recurrent RD in 32 (11.4%), giant retinal tear in 28 (10%), tractional
      RD in 15 (5.3%) and exudative RD in 2 (0.7%). Prophylactic laser or cryotherapy
      was applied in 74 (26.3%) of the eyes. Pars plana vitrectomy (PPV) was carried
      out in 159 (56.6%) eyes while scleral buckle procedure was done in 129 (45.9%)
      eyes. Silicon oil was used in 149 (53%), perfluorocarbon liquid in 32 (11.4%) and
      gas tamponade in 20 (7.1%) eyes. CONCLUSION: The most common cause of retinal
      detachment in paediatric patients was myopia, followed by trauma. Total RD was
      more common as compared to the other types. The most common procedure adopted was
      pars plana vitrectomy followed by scleral buckle procedure.

PMID- 23552536
TI  - Assessment of margins in resection specimens for head and neck malignancies.
AB  - OBJECTIVE: To determine the relative frequency of clear, close and involved
      margins in resection specimens for head and neck malignancies. STUDY DESIGN: An
      observational study. PLACE AND DURATION OF STUDY: The Department of Oral and
      Maxillofacial Surgery, Armed Forces Institute of Dentistry, Rawalpindi and the
      Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi,
      from January 2008 to December 2010. METHODOLOGY: Tumour registers and computer
      data bases in the department of Histopathology of Armed Forces Institute of
      Pathology, Rawalpindi, were analyzed for the cases of malignancies involving head
      and neck region that were sent for histopathological analysis after resection in
      the last three years. Histopathology reports were obtained. The data regarding
      age, gender, site, type of malignancy and margin status (clear, close or
      involved) was recorded on specially designed proformas for the study and later on
      analyzed by using SPSS version 17.0. Results were expressed. RESULTS: A total of
      319 cases were registered in the study duration. The age of the patients ranged
      from 22-90 years (mean 59.5 + 14.1 years). Male to female ratio was 1.53:1. One
      hundred and thirty six (42.6%) were squamous cell carcinoma (SCC), 163 were basal
      cell carcinomas (BCC, 51.0%); the rest included 18 salivary gland malignancies
      (5.7%) and one carcino-sarcoma (0.31%) and chondrosarcoma each. All margins were
      found clear in 137 patients (42.9%); involved in 168 cases (52.7%) and close in
      14 cases (4.4%). CONCLUSION: Margin clearance could not be achieved in more than
      50% cases, this can lead to poor prognosis. Hence, methods should be adopted to
      improve the margin clearance in various head and neck malignancies.

PMID- 23552537
TI  - Perceived childhood paternal acceptance-rejection among adults.
AB  - OBJECTIVE: To determine the childhood perceptual difference of paternal
      acceptance-rejection between those having psychological disorders and non
      clinical population during adulthood. STUDY DESIGN: Comparative study. PLACE AND
      DURATION OF STUDY: Karwan-e-Hayat, Psychiatric Care and Rehabilitation Centre,
      Keamari, Karachi, Pakistan, from January to August 2011. METHODOLOGY: To test our
      hypotheses, 69 participants were selected from Karwan-e-Hayat Psychiatric Care
      and Rehabilitation Centre, Karachi on the basis of purposive sampling technique
      and 79 from Karachi city on the basis of convenient sampling technique. To
      measure their perceived paternal acceptance-rejection during childhood, Adult
      Parental acceptance-rejection questionnaire (PARQ)/control: father-short form
      (Urdu translation) was administered. The statistical analysis of data was done
      with the predictive analytics software (PASW). RESULTS: One hundred and forty
      eight (78 males and 70 females) participants with mean age of 31.28 +/- 9.54
      years were included. Out of them 69 (40 males and 29 females) were clinical cases
      of depression, mania and psychosis with mean age of 33.26 +/- 9.51 years. Seventy
      nine (38 males and 41 females) were normal individuals with mean age of 29.54 +/-
      9.29 years of the demographics corresponding to the clinical population.
      Independent t-test revealed a significant difference in perceived childhood
      father acceptance-rejection between clinical and non-clinical population (p <
      0.05) and significant gender difference (p < 0.05). CONCLUSION: The studied
      clinical population and male participants perceived to be more rejected by their
      father during their childhood than non-clinical population and female
      participants.

PMID- 23552538
TI  - Outcome of end-to-end urethroplasty in post-traumatic stricture of posterior
      urethra.
AB  - OBJECTIVE: To determine the outcome of delayed end-to-end anastomotic
      urethroplasty in blind post-traumatic stricture of posterior urethra at our
      setup. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of
      Urology and Renal Transplantation, Quaid-e-Azam Medical College/Bahawal Victoria
      Hospital, Bahawalpur, from January 2009 to June 2011. METHODOLOGY: Adult patients
      with completely obliterated post-traumatic stricture of posterior urethra <= 2 cm
      were included in the study. Patients with post-prostatectomy (TUR-P, TVP)
      stricture, stricture more than 2 cm in size or patients of stricture with
      neurogenic bladder and patients with any perineal disease were excluded from the
      study. Retrograde urethrogram and voiding cysto-urethrogram was done in every
      patient to assess stricture length and location. Stricture excision and delayed
      end-to-end anastomosis of urethra with spatulation was performed in every
      patient. Minimum followup period was 6 months and maximum 18 months. RESULTS:
      There were 26 cases with road traffic accident (indirect) and 14 had history of
      fall/direct trauma to perineum or urethra. Majority of the patients (57.5%) were
      between 16 to 30 years of age. Twelve (30.0%) patients developed complications
      postoperatively. Early complications of wound infection occurred in 01 (2.5%)
      patient. Late complications were seen in 11 (27.5%) patients i.e. stricture
      recurrence in 7 (17.5%), erectile dysfunction in 2 (5.0%), urethrocutaneous
      fistula and urinary incontinence in one patient (2.5%) each. Success rate was
      70.0% initially and 87.5% overall. CONCLUSION: Delayed end-to-end anastomotic
      urethroplasty is an effective procedure for traumatic posterior urethral
      strictures with success rate of about 87.5%.

PMID- 23552539
TI  - Knowledge and reported practice of antibiotic prescription by dentists for common
      oral problems.
AB  - OBJECTIVE: To assess the knowledge and reported practice in relation to
      antibiotic prescribing regarding common oral problems by dentists in Karachi,
      Pakistan. STUDY DESIGN: Cross-sectional survey. PLACE AND DURATION OF STUDY:
      Three Dental Colleges of Karachi, from July to December 2010. METHODOLOGY: The
      cross-sectional study was conducted in Karachi, Pakistan in the Outpatient
      Departments (OPD) of three dental colleges. Inclusion criteria were full time
      employed dentists working in their respective OPDs (n = 100). The dentists were
      asked to fill a questionnaire. The questionnaire included (i) general
      information, (ii) perception and knowledge of antibiotic resistance, (iii)
      reported management of oral problems, (iv) perceptions about oral infections and
      (v) perceptions of how people perceive oral problems. To assess dentists' ability
      to relate knowledge to practice regarding the management of the most common oral
      problems, written simulated case scenarios with related questions were also
      included. Scores were given for each correct answer. RESULTS: The response rate
      was 85%. Of the total respondents, 65 (76%) were under the age of 30 years, 53
      (62%) were males and 32 (38%) females. Out of 85 respondents 53% (n = 45)
      reported prescribing of antibiotics 4-5 times a week, 87% (n = 74) prescribe
      antibiotics based upon symptoms and 64% (n = 54) prescribed antibiotics in
      abscess condition. The total score for all four scenarios showed that nearly two
      thirds (61%) of all respondents scored sub-optimally. CONCLUSION: A substantial
      number of dentists had suboptimal knowledge regarding antibiotic use. This might
      lead to the provision of suboptimal care of patients with dental infections.
      Therefore, continuing education, training and supervision are recommended to
      improve the quality of dental management.

PMID- 23552540
TI  - Primary neuroendocrine carcinoma of the breast.
AB  - Primary neuroendocrine carcinoma of the breast (NECB) is an extremely rare
      variant of breast cancer having aggressive clinicopathological behaviour and poor
      prognosis. A 62 years old woman presented with a painless lump in the left
      breast. Microscopic and immunohistochemical evaluation of the core-tissue biopsy
      and of the mastectomy specimen revealed moderately-differentiated neuroendocrine
      carcinoma of the breast. She was labeled as a case of primary neuroendocrine
      carcinoma of the breast after an infallible exclusion of any concomitant lesion
      elsewhere in the body. Modified radical mastectomy with level II axillary
      clearance, chemoradiotherapy and Famoxifen have led to an uneventful 5-year
      survival till the last follow-up.

PMID- 23552541
TI  - Breast sarcoma.
AB  - Breast sarcoma is a very rare mesenchymal tumour and accounts for about 0.5% of
      the total breast malignancies. We present the case of a 69 years old female who
      presented with a painful breast lump. The report highlights the pre-operative
      tests and the operative approach adopted for this patient. Surgical resection is
      recommended, although debate exists about the extent of surgery. Neo adjuvant
      chemotherapy and radiotherapy has been advised in certain cases but their role is
      still not clear. Further work is needed to standardize the treatment.

PMID- 23552542
TI  - Invaginated Meckel's diverticulum: a rare cause of small intestine
      intussusception in adults.
AB  - Intussusception is commonly seen in infants. It is occasionally found in adults
      usually due to carcinomas, colonic diverticuli, polyps and rarely Meckel's
      diverticulum. An adult male presented with upper abdominal pain, nausea, anorexia
      and loose stools. The initial investigative workup was unremarkable and patient
      responded to treatment given for acute gastroenteritis. After 3 days, the pain
      recurred in right iliac fossa with rebound tenderness and leukocytosis. Surgery
      was performed with provisional diagnoses of acute appendicitis and/or acute
      Meckel's diverticulitis. Per-operative findings revealed invaginated Meckel's
      diverticulum causing non-obstructing intussusception.

PMID- 23552543
TI  - Carcinoma multiplex.
AB  - Multiple primaries in a single patient are uncommon, though not very rare. The
      existence of such cancers in two un-related, non-paired organs is even more un
      common. Here, we present a case of 55 years old male who presented to us with a
      mucoepidermoid carcinoma of the parotid gland and was operated. Later on, he
      presented with a large cystic swelling in the pelvis which turned out to be
      pseudomyxoma peritonei. A review of slides and immunohistochemistry indicated it
      to be adenocarcinoma colon. He presented again with recurrent mucoepidermoid
      carcinoma of the parotid which was operated successfully with the use of
      myocutaneous flap for wound closure. He is currently undergoing chemotherapy. In
      order to establish a separate mono-clonal etiology of both tumours,
      immunohistochemistry was performed. To the best of our knowledge, carcinoma
      multiplex in the colon and the parotid has never been reported before.

PMID- 23552544
TI  - Ghost spell or hematohidrosis.
AB  - Hematohidrosis is a rare condition of excreting blood in sweat, tears or any
      other part of the body, with varied underlying etiologies and variable success to
      different available treatment modalities. We are reporting one such case of an
      adult female who could secrete blood from eyes and ears simultaneously either due
      to crying as a result of emotional outburst or even sometimes voluntarily.
      Considering her origin from tribal culture, she was often thought to be victim of
      some evil spell. The lady had taken various spiritual treatments from Pirs and
      various forms of medical treatments from homeopaths, quacks and medical doctors,
      but of no relief. She was treated for 2 months with non-selective beta blocker
      (propanolol 10 mg thrice daily) along with psychotherapy. She did improve
      symptomatically but did not get complete cure. Eventually she was lost to follow
      up as is common in female patients of tribal background. To our knowledge, this
      is the first such reported case from Pakistan.

PMID- 23552545
TI  - Creutzfeldt Jakob disease.
AB  - A case of 50 years of age, male with sporadic Creutzfeldt Jakob Disease (sCJD) is
      reported. Patient had dementia, behavioural abnormalities, unsteady gait and
      myoclonic jerks. Magnetic resonance imaging (MRI) brain T2 weighted and Fluid
      Attenuated Inverse Recovery (FLAIR) images showed abnormally increased signal
      intensity in caudate nucleus and putamen. Scalp electroencephalogram (EEG)
      revealed periodic synchronous biphasic sharp wave complexes. On the basis of
      history, clinical findings, typical MRI brain and EEG changes, diagnosis of
      sporadic CJD was made.

PMID- 23552546
TI  - Ogilvie's syndrome (acute colonic pseudo-obstruction) after caesarean section.
AB  - Ogilvie's syndrome (OS), a massive dilation of the colon in the absence of
      mechanical obstruction, is a rare postsurgical complication. The high mortality
      rate (normally 15-31% and upto 45% after caecal perforation) explains the
      seriousness of this clinical situation. Early diagnosis is made by plain
      abdominal X-ray and CT abdomen. Conservative treatment is usually effective and
      surgery should be reserved for complicated cases or refractory to conservative
      treatment. We report a case of 25 years primigravida who developed OS, 24 hours
      after cesarean section, which was treated by conservative methods.

PMID- 23552547
TI  - Divergent carpometacarpal fracture dislocation.
AB  - Divergent carpometacarpal fracture dislocation is a rare injury. We report a case
      affecting the medial four fingers of the left hand. The injury was sustained in a
      road traffic accident. The case was diagnosed with anteroposterior and lateral
      views on X-rays. He underwent open reduction supplemented with Kirschner wire
      fixation. This restored the normal carpometacarpal joint, anatomical relations
      and achieved an excellent clinical result in terms of function.

PMID- 23552548
TI  - Unusual presentation of gastric perforation in a neonate: subcutaneous emphysema
      and scrotal pneumatocele.
AB  - Gastric perforation in neonates is an uncommon condition. A four-day-male neonate
      was referred with respiratory distress, abdominal distention, right scrotal
      swelling and extensive emphysema of the abdominal wall. Abdominal X-ray findings
      showed bilateral sub-diaphragmatic free air, right scrotal pneumatocele and
      subcutaneous emphysema of the abdominal wall. During the operation, pre-pyloric
      perforation was determined. Primary repair by single layer suture was performed
      and postoperative period was uneventful.

PMID- 23552549
TI  - The need of paediatric dentistry specialists in Pakistan.
AB  - In the last decade, a rapid increase has been observed in the number of dentists
      due to establishment of a number of dental colleges in Pakistan. Very few of
      these institutions have Paediatric Dentistry Department. Similarly, no
      postgraduate Paediatric Dentistry training program exists in the two major
      provinces of the country. The objectives of this study were to map the pattern of
      paediatric dentistry services provided by the clinicians in teaching institutions
      and private practices. A cross-sectional study was conducted at dental
      departments of academic institutions and selected dental practices in Karachi.
      There was a statistically significant difference in preferences, selection of
      dental materials and pattern of paediatric dentistry services provided by the
      teaching dentists compared to the private practitioners. Both the teaching and
      non-teaching dentists need to update themselves in the provision of Paediatric
      Dentistry services such as fluoride application and fissure sealant placement.

PMID- 23552550
TI  - Utility of clinical examination and CT scan in assessment of penetrating neck
      trauma.
AB  - Managing penetrating injuries adequately and effectively depends a great deal on
      proper assessment of the injury. This study carried out was done at The Aga Khan
      University Hospital to assess the role of clinical examination and CT scan
      imaging in evaluation of penetrating neck injuries. A total of 68 students were
      included, with ages ranging from 3 to 74 years. The involved zones and the
      injured structures were noted. Results showed a high sensitivity of clinical
      examination in assessing vascular (81%) and airway trauma (77%), with a low
      sensitivity for esophageal trauma (34%). For CT scan the sensitivity was 90% for
      vascular trauma, 83% for airway trauma and 53% for esophageal injuries. Clinical
      findings and CT scan imaging are important assessment tools for evaluation of
      penetrating neck traumas, with a high sensitivity for vascular and airway
      injuries.

PMID- 23552551
TI  - Paradoxical ascites during antituberculous chemotherapy.

PMID- 23552552
TI  - "T2 shine through effect" of vasogenic oedema on DWI.

PMID- 23552553
TI  - Letter to editor regarding the case report "Posterior reversible encephalopathy
      syndrome (PRES)".

PMID- 23552555
TI  - MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) of the skin represents the most common malignancy in
      humans. MicroRNAs (miRNAs), small regulatory RNAs with pleiotropic function, are
      commonly misregulated in cancer. Here we identify miR-203, a miRNA abundantly and
      preferentially expressed in skin, to be downregulated in BCCs. We show that
      activation of the Hedgehog (HH) pathway, critically involved in the pathogenesis
      of BCCs, as well as the EGFR/MEK/ERK/c-JUN signaling pathway suppresses miR-203.
      We identify c-JUN, a key effector of the HH pathway, as a novel direct target for
      miR-203 in vivo. Further supporting the role of miR-203 as a tumor suppressor, in
      vivo delivery of miR-203 mimics in a BCC mouse model results in the reduction of
      tumor growth. Our results identify a regulatory circuit involving miR-203 and c
      JUN, which provides functional control over basal cell proliferation and
      differentiation. We propose that miR-203 functions as a 'bona fide' tumor
      suppressor in BCC, whose suppressed expression contributes to oncogenic
      transformation via derepression of multiple stemness- and proliferation-related
      genes, and its overexpression could be of therapeutic value.

PMID- 23552556
TI  - Regulation of subcellular distribution and oncogenic potential of nucleophosmin
      by plakoglobin.
AB  - Nucleophosmin (NPM) is a nucleolar phosphoprotein that is involved in many
      cellular processes and has both oncogenic and growth suppressing activities. NPM
      is localized primarily in nucleoli but shuttles between the nucleus and the
      cytoplasm, and sustained cytoplasmic distribution contributes to its tumor
      promoting activities. Plakoglobin (PG, gamma-catenin) is a homolog of beta
      catenin with dual adhesive and signaling functions. These proteins interact with
      cadherins and mediate adhesion, while their signaling activities are regulated by
      association with various intracellular partners. Despite these similarities, beta
      catenin has a well-defined oncogenic activity, whereas PG acts as a
      tumor/metastasis suppressor through unknown mechanisms. Comparison of the
      proteomic profiles of carcinoma cell lines with low- or no PG expression with
      their PG-expressing transfectants has identified NPM as being upregulated upon PG
      expression. Here, we examined NPM subcellular distribution and in vitro
      tumorigenesis/metastasis in the highly invasive and very low PG expressing MDA-MB
      231 (MDA-231) breast cancer cells and their transfectants expressing increased PG
      (MDA-231-PG) or NPM shRNA (MDA-231-NPM-KD) or both (MDA-231-NPM-KD+PG). Increased
      PG expression increased the levels of nucleolar NPM and coimmunoprecipitation
      studies showed that NPM interacts with PG. PG expression or NPM knockdown
      decreased the growth rate of MDA-231 cells substantially and this reduction was
      decreased further in MDA-231-NPM-KD+PG cells. In in vitro
      tumorigenesis/metastasis assays, MDA-231-PG cells showed substantially lower and
      MDA-231-NPM-KD cells substantially higher invasiveness relative to the MDA-231
      parental cells, and the co-expression of PG and NPM shRNA led to even further
      reduction of the invasiveness of MDA-231-PG cells. Furthermore, examination of
      the levels and localization of PG and NPM in primary biopsies of metastatic
      infiltrating ductal carcinomas revealed coordinated expression of PG and NPM.
      Together, the data suggest that PG may regulate NPM subcellular distribution,
      which may potentially change the function of the NPM protein from oncogenic to
      tumor suppression.

PMID- 23552557
TI  - MLK4beta functions as a negative regulator of MAPK signaling and cell invasion.
AB  - Mixed lineage kinase (MLK) 4, or MLK4, is a member of the MLK family of mitogen
      activated protein kinase kinase kinases (MAP3Ks). Typically, MAP3Ks function to
      activate the mitogen-activated protein kinase (MAPK)-signaling pathways and
      regulate different cellular responses. However, here we report that MLK4beta,
      unlike the other MLKs, negatively regulates the activities of the MAPKs, p38, c
      Jun N-terminal kinase and extracellular signal-regulated kinase, and the MAP2Ks,
      MEK3 and 6. Our results show that MLK4beta inhibits sorbitol- and tumor necrosis
      factor-induced activation of p38. Furthermore, MLK4beta interacts with another
      MLK family member, MLK3, in HCT116 cells. Exogenous expression of MLK4beta
      inhibits activation of MLK3 and also blocks matrix metalloproteinase-9 gelatinase
      activity and invasion in SKOV3 ovarian cancer cells. Collectively, our data
      establish MLK4beta as a novel suppressor of MLK3 activation, MAPK signaling and
      cell invasion.

PMID- 23552559
TI  - Photoelectrical properties and the electronic structure of Tl(1-x)In(1-x)Sn(x)Se2
      (x = 0, 0.1, 0.2, 0.25) single crystalline alloys.
AB  - Photoelectrical properties of Tl1-xIn1-xSnxSe2 single crystalline alloys (x = 0,
      0.1, 0.2, 0.25) grown using the Bridgman-Stockbarger method were studied. The
      temperature dependence of electrical and photoconductivity for the Tl1-xIn1
      xSnxSe2 single crystals was explored. It has been established that
      photosensitivity of the Tl1-xIn1-xSnxSe2 single crystals increases with x. The
      spectral distribution of photocurrent in the wavelength spectral range 400-1000
      nm has been investigated at various temperatures. Photoconductivity increases in
      all the studied crystals with temperature. Therefore, thermal activation of
      photoconductivity is caused by re-charging of the photoactive centers as the
      samples are heated. Based on our investigations, a model of center re-charging is
      proposed that explains the observed phenomena. X-ray photoelectron valence-band
      spectra for pristine and Ar(+)-ion irradiated surfaces of the Tl1-xIn1-xSnxSe2
      single crystals have been measured. These results reveal that the Tl1-xIn1
      xSnxSe2 single-crystal surface is sensitive to the Ar(+) ion irradiation that
      induced structural modification in the top surface layers. Comparison on a common
      energy scale of the X-ray emission Se Kbeta2 bands representing energy
      distribution of the Se 4p-like states and the X-ray photoelectron valence-band
      spectra was done.

PMID- 23552561
TI  - Clinically meaningful scores on pain catastrophizing before and after
      multidisciplinary rehabilitation: a prospective study of individuals with
      subacute pain after whiplash injury.
AB  - OBJECTIVES: Pain catastrophizing has emerged as a significant risk factor for
      problematic recovery after musculoskeletal injury. As such, there has been an
      increased focus on interventions that target patients' levels of catastrophizing.
      However, it is not presently clear how clinicians might best interpret scores on
      catastrophizing before and after treatment. Thus, the purpose of this study was
      to provide preliminary guidelines for the clinical interpretation of scores on
      pain catastrophizing among individuals with subacute pain after musculoskeletal
      injury. METHODS: A sample of 166 occupationally disabled individuals with
      subacute pain due to a whiplash injury participated in this study. Participants
      completed a 7-week standardized multidisciplinary rehabilitation program aimed at
      fostering functional recovery. Participants completed the Pain Catastrophizing
      Scale (PCS) upon program commencement and completion. One year later,
      participants indicated their pain severity and involvement in employment
      activities. Separate receiver operating characteristic curve analyses were
      conducted to determine absolute pretreatment and posttreatment and percent change
      scores on the PCS that were best associated with clinically important levels of
      pain and employment status at the follow-up. RESULTS: An absolute pretreatment
      PCS score of 24 best identified patients according to follow-up clinical
      outcomes. Posttreatment PCS scores of 14 and 15 best identified patients with
      high follow-up pain intensity ratings and those who did not return to work,
      respectively. PCS reductions of approximately 38% to 44% were best associated
      with return to work and low pain intensity ratings at follow-up. DISCUSSION: The
      results indicate scores on catastrophizing before and after treatment that are
      clinically meaningful. These results may serve as preliminary guidelines to
      assess the clinical significance of interventions targeting pain catastrophizing
      in patients with subacute pain after musculoskeletal injury.

PMID- 23552562
TI  - Reduced areas of spontaneous neuropathic pain after spinal cord stimulation
      treatment.
AB  - OBJECTIVES: Spinal cord stimulation (SCS) is known to be an effective treatment
      for a range of neuropathic pain (NeP) conditions, although further clinical
      evidence is required. Clinical observations suggest that 1 aspect of the
      treatment effect is a reduction in the area with spontaneous NeP. The aim of this
      study was to quantify the areas of spontaneous NeP in SCS patients and to
      correlate these with changes in pain intensity and quality of life. METHODS:
      Twenty-six SCS patients with NeP rated their pain intensity on a numerical rating
      scale (0 to 10) and completed the SF-36 health survey. In addition, their areas
      of spontaneous pain were photographically documented before and during SCS
      treatment, and the areas were transferred to phantom drawings and digitally
      quantified. RESULTS: Areas of spontaneous NeP were reduced by 62% (interquartile
      range, -15 to 78). Pain intensity was reduced from 7.5 +/- 1.1 before to 4.9 +/-
      1.7 during treatment (mean +/- SD) and most domains of the SF-36 health survey
      also improved with SCS treatment. Using linear regression, no correlation was
      found between relative reduction in areas of spontaneous NeP and relative
      reduction in pain intensity as well as in absolute improvement in quality of life
      assessed by SF-36. A correlation was found between improvement in pain intensity
      and in quality of life. DISCUSSION: The results indicate that the main impact of
      SCS on the patients' quality of life is not the reduction of the painful areas,
      but rather the reduced pain intensity in the remaining area.

PMID- 23552563
TI  - Placement of an intrathecal catheter through a bony fusion mass using 3D image
      guidance: a case report.
AB  - OBJECTIVE: We describe the 3-dimensional (3D) image-guided placement technique
      for a lumbar intrathecal catheter through a dorsal fusion mass. This is the first
      time this technique has been reported. A patient with 6 prior spine surgeries and
      chronic pain syndrome presented with a challenging large dorsal fusion mass. The
      use of 3D cone beam computed tomography-based image guidance proved advantageous
      for the placement of an intrathecal drug delivery system (IDDS). METHOD: Under
      general anesthesia, image guidance was accomplished with the Medtronic Stealth S7
      image guidance system, used in conjunction with the O-ARM (Medtronic Inc.). Using
      an image-guided probe over the skin surface, we navigated the dorsal fusion mass
      to identify a thin area at the L4-L5 level. A small incision was made and the
      image-guided probe was used to target the selected thin area and drill an
      adequate opening in the fusion mass. We inserted a Tuohy needle through the bony
      defect for passage of the intrathecal catheter. We confirmed adequate catheter
      placement using free flowing cerebrospinal fluid and fluoroscopy. The remainder
      of the IDDS implant proceeded per routine. RESULTS: The patient tolerated the
      procedure well and had no complications. The morphine IDDS improved his overall
      pain and function with minimal side effects. CONCLUSIONS: This is the first case
      report using 3D cone beam computed tomography-based image guidance for the
      placement of an intrathecal catheter through a bony fusion mass. This technique
      appears to be a viable option for IDDS implantation in patients with difficult
      anatomy.

PMID- 23552564
TI  - Exploration of 2, 4-diaminopyrimidine and 2, 4-diamino-s-triazine derivatives as
      potential antifilarial agents.
AB  - In view of the mandate from the World Health Organization (WHO) for developing
      novel drug candidates against human lymphatic filariasis, dihydrofolate reductase
      (DHFR) inhibitors are explored as potential antifilarial agents. The in vitro
      biological evaluation of an in-house library of 12 diverse antifolate compounds
      with 2,4-diaminopyrimidine and 2,4-diamino-s-triazine structural features against
      Brugia malayi is reported. To confirm the DHFR inhibitory potential of these
      compounds, reversal studies using folic acid and folinic acid were undertaken.
      Inhibition of DHFR can induce apoptosis; in this light, preliminary evidence of
      apoptosis by test compounds was detected using ethidium bromide-acridine orange
      staining and the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition
      assay. Among the evaluated compounds, 3 showed significant activity against both
      microfilariae and adult worms. The effects of 2 of these compounds were mostly
      reversed by folic acid, validating DHFR inhibitory activity. Partial reversal of
      the effect of 2 compounds by folinic acid and non-reversal of the effect of the
      third compound both by folic and folinic acids are discussed. This study opens
      new avenues for the discovery of lead molecules by exploiting the folate pathway
      against one of the major neglected tropical diseases, filariasis.

PMID- 23552565
TI  - Effects of sevoflurane postconditioning on cell death, inflammation and TLR
      expression in human endothelial cells exposed to LPS.
AB  - BACKGROUND: Sevoflurane is an anesthetic agent which also participates in
      protective mechanisms in sepsis, likely due to anti-inflammatory properties. A
      key tissue in sepsis is the endothelium, which expresses TLR2 and TLR4 receptors,
      known regulators of inflammatory mechanisms and potential therapeutic targets for
      this pathology. In this context, we explored the effect of sevoflurane
      postconditioning in an in vitro sepsis model. METHODS: Primary cultures of human
      umbilical vein endothelial cells were used for two different experiments. In the
      first set, cultures were placed in an airtight incubation chamber and exposed to
      different concentrations of sevoflurane (0,1,3 or 7% vol,) for 1 hour. In the
      second set, lipopolysaccharide from Escherichia coli 0111:B4 (1 MUg/mL) was added
      to culture medium for 3 hours and cells were subsequently exposed to sevoflurane
      (0,1,3 or 7% vol,) for 1 hour as explained before. In both cases, cell viability
      was measured by MTT and Trypan blue assays, TLR2 and TLR4 expression were
      analyzed by flow cytometry, and TNFalpha and IL-6 levels were quantified in cell
      culture media by an immunoassay immediately after exposure, at 6 and 24 hours.
      RESULTS: Exposure to 3% sevoflurane decreased TLR2 at 24 hours and TLR4 at 6 and
      24 hours (both p<0.05), whereas exposure to 7% decreased TLR4 expression at 6
      hours (p<0.05). Both 3 and 7% sevoflurane decreased TNF-alpha and IL-6 levels at
      24 hours (both p<0.05). In LPS-stimulated cultures, exposure to 3% sevoflurane
      was cytoprotective at 6 and 24 hours (p<0.05) compared with control, and
      decreased TLR2 and TLR4 expression at 24 hours (p<0.05); whereas 7% decreased
      TLR4 expression at 24 hours (p<0.05). Both 3% and 7% sevoflurane decreased TNF
      alpha and IL-6 levels at 24 hours (both p<0.05). CONCLUSIONS: Postconditioning
      with the halogenated anesthetic agent sevoflurane after LPS stimulation shows a
      cytoprotective effect in an in vitro model, decreasing cell death and reducing
      TLR2 and TLR4 expression as well as levels of the inflammatory mediators TNF
      alpha and IL-6 in human endothelial cells.

PMID- 23552568
TI  - Long-range Li+ dynamics in the lithium argyrodite Li7PSe6 as probed by rotating
      frame spin-lattice relaxation NMR.
AB  - Lithium-rich argyrodites belong to a relatively new group of fast ion conducting
      solids. They might serve as powerful electrolytes in all-solid-state lithium-ion
      batteries being, from a medium-term point of view, the key technology when safe
      energy storage systems have to be developed. Spin-lattice relaxation (SLR)
      nuclear magnetic resonance (NMR) measurements carried out in the rotating frame
      of reference turned out to be the method of choice to study Li dynamics in
      argyrodites. When plotted as a function of the inverse temperature, the SLR rates
      log10(R1rho) reveal an asymmetric diffusion-induced rate peak. The rate peak
      contains information on the Li jump rate, the activation energy of the hopping
      process as well as correlation effects. In particular, considering the high
      temperature flank of the SLR NMR rate peak recorded in the rotating frame of
      reference, an activation energy of approximately 0.49 eV is found. This value
      represents long-range lithium jump diffusion in crystalline Li7PSe6. As an
      example, at 325 K the Li jump rate determined from SLR NMR is in the order of 1.4
      * 10(5) s(-1). The pronounced asymmetry of the rate peak R1rho(1/T) points to
      correlated Li motion. It is comparable to that which is typically found for
      structurally disordered materials showing a broad range of correlation times.

PMID- 23552567
TI  - A case of inflammatory nonscarring alopecia associated with the tyrosine kinase
      inhibitor nilotinib.
AB  - IMPORTANCE: Nilotinib, a recently approved multitargeted tyrosine kinase
      inhibitor targeting the BCR-Abl translocation involved in chronic myelogenous
      leukemia, reportedly produces alopecia according to the package insert, but
      clinical and histologic descriptions of the alopecia are lacking. OBSERVATIONS: A
      33-year-old woman with chronic myelogenous leukemia developed widespread alopecia
      involving scalp and body hair within weeks after starting nilotinib therapy.
      Biopsies revealed perifollicular lymphocytic inflammation and evidence of
      follicular injury but normal hair density, consistent with a nonscarring
      alopecia. CONCLUSIONS AND RELEVANCE: Nilotinib therapy may induce perifollicular
      inflammation and widespread persistent alopecia. We present the first clinical
      and histologic description of this potential adverse effect. Further
      investigation into the underlying mechanism of this adverse effect may produce
      insights into the hair growth cycle as well as potential therapeutic targets.

PMID- 23552569
TI  - Quantitative comparison of 3D and 2.5D gamma analysis: introducing gamma angle
      histograms.
AB  - Comparison of dose distributions using the 3D gamma method is anticipated to
      provide better indicators for the quality assurance process than the 2.5D
      (stacked 2D slice-by-slice) gamma calculation, especially for advanced
      radiotherapy technologies. This study compares the accuracy of the 3D and 2.5D
      gamma calculation methods. 3D and 2.5D gamma calculations were carried out on
      four reference/evaluation 3D dose sample pairs. A number of analysis methods were
      used, including average gamma and gamma volume histograms. We introduce the
      concept of gamma-angle histograms. Noise sensitivity tests were also performed
      using two different noise models. The advantage of the 3D gamma method showed up
      as a higher proportion of points passing the tolerance criteria of 3% dose
      difference and 3 mm distance-to-agreement (DTA), with considerably lower average
      gamma values, a lower influence of the DTA criterion, and a higher noise
      tolerance. The 3D gamma approach is more reliable than the 2.5D approach in terms
      of providing comprehensive quantitative results, which are needed in quality
      assurance procedures for advanced radiotherapy methods.

PMID- 23552570
TI  - An in situ spatially resolved analytical technique to simultaneously probe gas
      phase reactions and temperature within the packed bed of a plug flow reactor.
AB  - This paper reports the detailed description and validation of a fully automated,
      computer controlled analytical method to spatially probe the gas composition and
      thermal characteristics in packed bed systems. As an exemplar, we have examined a
      heterogeneously catalysed gas phase reaction within the bed of a powdered oxide
      supported metal catalyst. The design of the gas sampling and the temperature
      recording systems are disclosed. A stationary capillary with holes drilled in its
      wall and a moveable reactor coupled with a mass spectrometer are used to enable
      sampling and analysis. This method has been designed to limit the invasiveness of
      the probe on the reactor by using the smallest combination of thermocouple and
      capillary which can be employed practically. An 80 MUm (O.D.) thermocouple has
      been inserted in a 250 MUm (O.D.) capillary. The thermocouple is aligned with the
      sampling holes to enable both the gas composition and temperature profiles to be
      simultaneously measured at equivalent spatially resolved positions. This analysis
      technique has been validated by studying CO oxidation over a 1% Pt/Al2O3 catalyst
      and the spatial resolution profiles of chemical species concentrations and
      temperature as a function of the axial position within the catalyst bed are
      reported.

PMID- 23552571
TI  - Role of nucleation-promoting factors in mouse early embryo development.
AB  - During mitosis nucleation-promoting factors (NPFs) bind to the Arp2/3 complex and
      activate actin assembly. JMY and WAVE2 are two critical members of the NPFs.
      Previous studies have demonstrated that NPFs promote multiple processes such as
      cell migration and cytokinesis. However, the role of NPFs in development of
      mammalian embryos is still unknown. Results of the present study show that the
      NPFs JMY and WAVE2 are critical for cytokinesis during development of mouse
      embryos. Both JMY and WAVE2 are expressed in mouse embryos. After injection of
      JMY or WAVE2 siRNA, all embryos failed to develop to the morula or blastocyst
      stages. Moreover, using fluorescence intensity analysis, we found that the
      expression of actin decreased, and multiple nuclei were observed within a single
      cell indicating that NPFs-induced actin reduction caused the failure of cell
      division. In addition, injection of JMY and WAVE2 siRNA also caused ARP2
      degradation, indicating that involvement of NPFs in development of mouse embryos
      is mainly through regulation of ARP2/3-induced actin assembly. Taken together,
      these data suggested that WAVE2 and JMY are involved in development of mouse
      embryos, and their regulation may be through a NPFs-Arp2/3-actin pathway.

PMID- 23552572
TI  - High variation between hospitals in vena cava filter use for venous
      thromboembolism.
AB  - BACKGROUND: The extent to which vena cava filter (VCF) use varies between
      hospitals in the management of acute venous thromboembolism (VTE) is not clear.
      METHODS: We conducted a retrospective observational study that compared the
      frequency of VCF use among California hospitals from January 1, 2006, through
      December 31, 2010. Using administrative hospital discharge data, we followed
      explicit criteria to identify nontrauma patients with acute VTE, and determined
      the frequency of VCF placement in each of the hospitals that admitted more than
      55 VTE patients. Multivariable hierarchical regression models to predict VCF use
      included important clinical and demographic variables as fixed effects and
      hospital as a random effect. RESULTS: Among the 263 hospitals included, 130 643
      acute VTE hospitalizations occurred with the placement of 19 537 VCFs (14.95%).
      Variation in the percentage of acute VTE hospitalizations that included VCF
      placement was very high, from 0% to 38.96% (interquartile range, 6.23%-18.14%),
      with 18.49% of the observed variation due to differences among the hospitals that
      provided care. Significant clinical predictors of VCF use included acute bleeding
      at the time of admission (odds ratio, 3.4 [95% CI, 3.2-3.6]), a major operation
      after admission for VTE (3.4 [3.3-3.5]), presence of metastatic cancer (1.7 [1.6
      1.8]), and extreme severity of illness (2.5 [2.3-2.7] vs mild). Insertion of VCFs
      occurred more frequently than expected in 109 hospitals and less frequently in
      59. Hospital characteristics associated with VCF use included a small number of
      beds (odds ratio, 0.2 [95% CI, 0.2-0.4], <100 vs >400 beds), a rural location
      (0.4 [0.2-0.5]), and other private vs Kaiser hospitals (1.5 [1.1-2.0]). Use of
      VCFs varied widely even in geographically proximate areas. CONCLUSIONS: The
      frequency of VCF use in patients with acute VTE varied widely and depended on
      which hospital provided the care, even after adjusting for clinical and
      socioeconomic factors. Further research is needed to determine whether this
      variation is associated with local cultural differences between hospitals or with
      differences in the availability of interventional radiologists or specialists, or
      whether it reflects the absence of high-quality evidence that VCFs are effective.

PMID- 23552575
TI  - Consensus from the 7th European Bifurcation Club meeting.

PMID- 23552576
TI  - A corticotropin-releasing factor receptor antagonist improves urodynamic
      dysfunction produced by social stress or partial bladder outlet obstruction in
      male rats.
AB  - Barrington's nucleus, in the pons, regulates micturition through spinal
      projections to preganglionic parasympathetic neurons. The stress neuropeptide CRF
      is prominent in these projections and has an inhibitory influence. Social stress
      in rats causes urinary retention and abnormal urodynamics resembling those
      produced by partial bladder outlet obstruction (pBOO), and this is associated
      with CRF upregulation in Barrington's nucleus. Here, we examined the role of CRF
      in social stress- and pBOO-induced urodynamic dysfunction by assessing the
      ability of a CRF1 receptor antagonist to alter these effects. Male rats exposed
      to repeated resident-intruder stress were administered vehicle or a CRF1
      antagonist (NBI-30775) daily prior to the stress. Urodynamic function was
      recorded in the unanesthetized state 72 h after the final stress. NBI-30775
      prevented the increased intermicturition interval, micturition volume, and
      bladder capacity produced by social stress, but not the increase in CRF
      expression in Barrington's nucleus neurons. The urinary dysfunction was also
      partly prevented by shRNA targeting of CRF in Barrington's nucleus, suggesting
      that stress-induced urinary dysfunction results, in part, from CRF upregulation
      in Barrington's nucleus and enhanced postsynaptic effects in the spinal cord.
      Finally, NBI-30775 improved urodynamic function of rats that had pBOO of 2-wk
      duration when administered daily during the second week but did not block the
      increase in CRF expression in Barrington's nucleus neurons. These findings
      implicate a role for Barrington's nucleus CRF in stress- and pBOO-induced
      urodynamic changes and suggest that CRF1 antagonists may be useful therapeutic
      agents for the treatment of urinary dysfunction.

PMID- 23552577
TI  - A clinical study to assess the effectiveness of a hyaluronic acid-based procedure
      for treatment of premature ejaculation.
AB  - Premature ejaculation is a sexual debilitating condition affecting a large number
      of men worldwide and leading to important dysfunctions influencing the patients'
      affective and emotional life. Hyaluronic acid is a natural and safe compound that
      has been widely used not only in the aesthetic medicine clinic, but also for
      treatment of osteoarthritis. The present study shows the effectiveness of a
      hyaluronic acid-based procedure for treatment of premature ejaculation. A hundred
      and ten male patients were treated with hyaluronic acid injections in the deep
      dermis of their glans penis to increase the volume and the circumference of their
      penis to prevent male premature ejaculation and improve the patients' and their
      partners' sexual satisfaction. The intravaginal ejaculation latency time
      increased significantly from a baseline value of 88.34+/-3.14 s to 293.14+/-8.16
      s after 6 months from the procedure. Maximal glandular circumference increased
      from 98.51+/-0.71 mm to 114.35+/-0.66 mm after 6 months from the procedure. At 6
      month follow-up, patients' self-rated satisfaction was 5.3+/-0.07 (range: 4-6).
      At the follow-up, partners' self-rated satisfaction was 5.1+/-0.09 (range: 3-6).
      The present clinical study showed that hyaluronic acid injection is a promising
      treatment for premature ejaculation. The effect of the procedure in the long-term
      follow-up needs to be clarified.

PMID- 23552578
TI  - Which is guilty in self-induced penile fractures: marital status, culture or
      geographic region? A case series and literature review.
AB  - Penile fracture is a well-recognized and relatively uncommon clinical entity. It
      was previously reported that the incidence of penile fracture varies according to
      various geographic regions. In order to determine whether marital status or
      culture other than geographic region is involved in the etiology of penile
      fracture in our country, the charts of 122 men diagnosed with penile fracture
      were retrospectively reviewed. Detailed history including cause, symptoms,
      country of origin and a single-question self-report of erectile dysfunction was
      used for all cases. Diagnosis of our cases was mainly based on history and
      physical examination and ultrasonography. Immediate or delayed surgical repair of
      penile fracture included a degloving circumferential, and an additional direct
      incision, if the site of the tear could not be reached via degloving, was
      performed. The patients were evaluated after 1 week and 1, 3, and 6 months follow
      up by penile examination, recording complications, and with a single-question
      self-report questionnaire after 3 and 6 months. The most common cause of penile
      fracture was manual bending of the erected penis in 66 out of 122 (54.1%) of our
      study patients. In our study, we believe that the prime causes of bending the
      penis are single status and culture, which are influencing factors irrespective
      of the geographic distribution. 

PMID- 23552579
TI  - A nationwide population-based study on bladder pain syndrome/interstitial
      cystitis and ED.
AB  - As bladder pain syndrome/interstitial cystitis (BPS/IC) has been demonstrated to
      proceed through the inflammatory pathways to cause endothelial dysfunction, and
      endothelial dysfunction is a major factor in the development of ED, it is
      possible that BPS/IC may be associated with ED. This study set out to investigate
      the putative association between ED and BPS/IC by using a population-based data
      set and case-control design in Taiwan. We obtained the data from Taiwan's
      National Health Insurance Research Database. Cases included 32,856 ED patients >=
      18-years old and 164,280 matched controls. Conditional logistic regression
      analyses were performed to compare the odds ratios (OR) and corresponding 95%
      confidence intervals (CIs) of having been previously diagnosed with BPS/IC in
      cases and controls. Among the total sample of 197,136 subjects, the prevalence of
      prior BPS/IC was 0.05%. The prevalence of prior BPS/IC was 0.10% and 0.04% for
      cases and controls, respectively (P<0.001). Conditional logistic regression
      analysis revealed that when compared with controls, the OR of prior BPS/IC for
      cases was 1.75 (95% CI=1.12-2.71) after adjusting for monthly income, geographic
      location, hypertension, diabetes, coronary heart disease, hyperlipidemia, renal
      disease, obesity, depressive disorder, alcohol abuse/alcohol-dependence syndromes
      and the number of outpatient visits within 1 year before index date. Subjects
      aged between 18 and 39 were additionally found to have the highest ORs for prior
      BPS/IC among cases when compared with controls (OR=10.40; 95% CI=2.93-36.94).
      There was an association between BPS/IC and ED. The youngest cases with ED were
      found to have the strongest magnitudes of association with BPS/IC.

PMID- 23552580
TI  - Effects of long-term high dose testosterone administration on vaginal epithelium
      structure and estrogen receptor-alpha and -beta expression of young women.
AB  - To date, the effects of long-term testosterone (T) administration on the human
      vagina are not completely understood. Thus, the aim of this study was to
      investigate the effects of long-term T treatment on vaginal tissue histology,
      estrogen receptor alpha (ERalpha) and beta (ERbeta) expression and proliferation
      in female to male transsexual subjects (FtM). We compared vaginal samples from
      FtM subjects with those of premenopausal women (PrM) and postmenopausal women (M)
      not receiving any hormonal treatment for at least 2 years. Vaginal tissue samples
      from 16 FtM subjects treated with T (intramuscular injections of 100 mg
      Testoviron Depot/7-10 days for at least 1 year), undergoing sex reassignment
      surgery, and 16 PrM and 16 M subjects undergoing a vaginal hysterectomy for
      prolapse, were collected. For each sample, morphology, glycogen content,
      proliferation (ki-67), ERalpha and ERbeta expression were evaluated. Vaginal
      samples from FtM showed a loss of normal architecture of the epithelium,
      intermediate and superficial layers were completely lost, and glycogen content
      was depleted. T administration resulted in a strong proliferation reduction when
      compared with both M and PrM subjects. Stromal and epithelial ERalpha as well as
      ERbeta were significantly decreased in FtM when compared with PrM subjects. In
      conclusion, our data suggests that systemic T administration at
      supraphysiological dosage, determines profound changes in histomorphology and
      reduces ERs expression and proliferation of vaginal epithelium. 

PMID- 23552581
TI  - Association between ED in ankylosing spondylitis: a population-based study.
AB  - Even though a growing number of studies have found that patients with ankylosing
      spondylitis (AS) suffer from sexual problems, only very few studies have
      specifically addressed the relationship between AS and ED. Using a population
      based data set, this case-control study aimed to examine the association of ED
      with a prior diagnosis of AS in Taiwan. We selected 2213 ED patients >=40 years
      old and 17,704 matched controls. We considered the date of the first diagnosis of
      ED as the index date for cases. Multivariate logistic regression was performed to
      calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for
      the association between previously diagnosed AS and ED. A total of 224 out of the
      19,917 sampled subjects (1.1%) had been diagnosed with AS before the index date.
      Prior AS was found in 42 (1.9%) cases and 182 (1.0%) controls. After adjusting
      for geographic location, urbanization level, hypertension, diabetes, coronary
      heart disease, hyperlipidemia, obesity, depressive disorder and alcohol
      abuse/alcohol-dependence syndrome, multivariate logistic regression revealed that
      cases were more likely to have been previously diagnosed with AS than controls
      (OR=1.58, 95% CI=1.09-2.19, P=0.019). There was an association between ED and AS.
      We suggest that physicians should be attentive to sexual complaints from AS
      patients in order to refer them to other specialists for multidisciplinary
      management.

PMID- 23552583
TI  - Three-dimensional deconvolution microfluidic microscopy using a tilted channel.
AB  - We have developed a microfluidic device that enables the computation of three
      dimensional (3-D) images of flowing samples. Using a microfluidic channel that is
      tilted along the optical axis, we record several progressively defocused images
      of the flowing sample as it passes across the focal plane. The resulting focal
      stack is then deconvolved to generate 3-D images. Experimental results on flowing
      yeast cells reveal both volume and surface profile information. The microfluidic
      channel eliminates the need for a precise translation stage to control defocusing
      and enables high sample throughput in an insulated, nontoxic, liquid environment.
      The experimental device can be implemented in all existing microscopes as a
      modified slide stage and is ideally suited for 3-D profiling in flow cytometers.

PMID- 23552584
TI  - Pressure-induced near infrared spectra response as a valuable source of
      information for soft tissue classification.
AB  - Acquiring near infrared spectra in vivo usually requires a fiber-optic probe to
      be pressed against the tissue. The applied pressure can significantly affect the
      optical properties of the underlying tissue, and thereby the acquired spectra.
      The existing studies consider these effects to be distortions. In contrast, we
      hypothesize that the pressure-induced spectral response is site- and tissue
      specific, providing additional information for the tissue classification. For the
      purpose of this study, a custom system was designed for dynamic pressure control
      and rapid acquisition of spectra. The pressure-induced spectral response was
      studied at three proximate skin sites of the human hand. The diffuse reflectance
      and scattering were found to decrease with the applied contact pressure. In
      contrast, the concentrations of chromophores, and consequently the absorption,
      increased with the applied contact pressure. The pressure-induced changes in the
      tissue optical properties were found to be site-specific and were modeled as a
      polynomial function of the applied contact pressure. A quadratic discriminant
      analysis classification of the tissue spectra acquired at the three proximate
      skin sites, based on the proposed pressure-induced spectral response model,
      resulted in a high (90%) average classification sensitivity and specificity,
      clearly supporting the working hypothesis.

PMID- 23552585
TI  - Depression in patients with colorectal cancer.
AB  - Patients with colorectal cancer (CRC) experience psychological stress due to the
      diagnosis and the physical and social changes brought on by the illness,
      increasing the risk of depressive disorder. Depression causes tremendous
      disability and adds to the suffering that patients must already endure. It is
      known to alter immune and endocrine functions that affect vulnerability to CRC,
      its course over time, and its response to treatment. We review the prevalence of
      depressive symptoms and disorders worldwide and in the Kingdom of Saudi Arabia
      (KSA), focusing on patients with medical illness and those with CRC, in
      particular. We examine how often depression is diagnosed, how it is treated, and
      its likely course over time, and review the effects of depression on functional
      disability, longevity, and immune functions. Finally, we discuss research needs
      and make recommendations on highest priority research studies to advance our
      understanding of depressive disorder in CRC patients in KSA.

PMID- 23552586
TI  - Preparing for the Objective Structured Clinical Examination (OSCE). Guide for
      students and residents.
AB  - The objective structured clinical examination (OSCE) has become an accepted
      method for evaluating clinical competence. Limited references are available for
      students and residents to help them prepare adequately for such examinations. In
      this review an outline on how to prepare, approach, and behave during the OSCE is
      presented. Students should prepare by repeated practice keeping in mind that the
      exam is usually divided into history and physical examination stations.
      Candidates should pay close attention to all given instructions and rules of the
      exam. During the encounter, proper interaction, and good communication with the
      patient and family are critical for a successful exam. At the end of the OSCE,
      candidates should avoid rushing the patient or asking for their mark. To
      conclude, careful preparation for the OSCE is needed to improve the likelihood of
      a successful outcome.

PMID- 23552587
TI  - Role of vitamins E and C in mitigating hypoxia- and exhaustive exercise-induced
      aberrant stem cell factor expression and impaired reproductive function in male
      Wistar rats.
AB  - OBJECTIVE: To evaluate and compare the potential role of vitamins E and C in
      protecting against acute swimming induced reproductive function damage at
      different altitudes. METHODS: The study was carried between October and November
      2010. A total of 36 adult male Wistar rats weighing 250+/-5 g, and aged 8 weeks
      were used in this study, which was carried at the Physiology laboratory of King
      Khalid University in Abha City (high altitude area [HA]), and at the College of
      Science, King Saud University in Riyadh city (low altitude area [LA]), Kingdom of
      Saudi Arabia. The rats of each area were divided into 3 groups (n=6 each):
      control, acute exercise stress, and vitamins E and C pretreated stress. At the
      end of the study, oxidative stress, reproductive function, histopathology, and
      expression of stem cell factor (CSF) were examined in all rats. RESULTS: Living
      under HA conditions decreased expression of SCF, sperm count, and serum levels of
      reproductive hormones, and significantly increased testicle tissue oxidative
      stress and lipid peroxidation. Exhaustive exercise-induced stress at both
      altitudes resulted in similar results with more deteriorating effects in rats of
      HA compared with LA. Supplementation of vitamins E and C prior to stress
      induction at both altitudes prevented all these structural and functional
      aberrations from happening. CONCLUSION: High altitude or strenuous exercise, or
      both, may impair male reproductive function, while vitamins E and C in
      combination potentially mitigate these adverse effects.

PMID- 23552588
TI  - The course of the marginal mandibular branch of the facial nerve in adult
      cadavers. An anatomic study.
AB  - OBJECTIVE: To observe the course of the marginal mandibular branch of the facial
      nerve (MMBFN) and its relation to the inferior border of the mandible and facial
      vessels. METHODS: This cadaveric study was conducted at the Department of
      Anatomy, Gulhane Military Medical Academy, Ankara, Turkey from April to September
      2012. The 44 facial halves of 22 adult cadavers were dissected under a
      stereomicroscope. RESULTS: The nerve was found to be presented by one branch
      (36.4%), and 2 branches (63.6%). The distance of the nerve from the inferior
      border of the mandible varied from 13.06-40.08 mm, with an average distance of
      21.91 mm. There were communications with buccal branch only in 2 specimens
      (4.6%). All the branches of the marginal mandibular branch ran laterally to the
      facial artery in 43 (97.7%) of the 44 specimens. In one specimen, the 2 marginal
      mandibular branches ran between the facial artery and vein. CONCLUSION: The MMBFN
      can occasionally be damaged during surgeries confined to the submandibular region
      due to its location and anatomical variant. The most common pattern of MMBFN was
      nerve with 2 branches. The maximum distance between the MMBFN and the mandible
      was 40.08 mm. This anatomical knowledge may be useful to surgeons of the head and
      neck in planning incisions and procedures in the submandibular region.

PMID- 23552589
TI  - Effects of dexmedetomidine on succinylcholine-induced myalgia in the early
      postoperative period.
AB  - OBJECTIVE: To determine the effects of dexmedetomidine on the incidence of
      fasciculation and myalgia, and to evaluate changes in creatine kinase levels due
      to succinylcholine administration. METHODS: Sixty patients undergoing direct
      laryngoscopy were enrolled in this study carried out in the Department of
      Anesthesiology and Reanimation, Hacettepe University, Ankara, Turkey between
      January and March 2010. Patients were allocated blindly to 3 anesthesiologists.
      In the dexmedetomidine group (group D) (n=30), dexmedetomidine 1ug/kg was
      administered intravenously over 10 minutes before the intubation. In the control
      group (group C) (n=30), the same volume of normal saline was administered.
      Laryngoscopy was performed one minute after administration of succinylcholine.
      Dexmedetomidine infusion was continued until the end of surgery. Fasciculation
      and myalgia at the postoperative thirtieth minute, and creatine kinase levels
      before the induction of anesthesia and at the postoperative 24th hour, and
      adequacy of relaxation for intubation were recorded. RESULTS: The severity and
      incidence of fasciculation were better in group D than group C (p=0.025).
      Intubating conditions were better in the dexmedetomidine group (p=0.011). At the
      thirtieth minute, the incidence and severity of myalgia were significantly higher
      in group C (p=0.014). Postoperative creatine kinase levels increased
      significantly compared with their base-line levels in both groups (p=0.022 in
      group D and p=0.017 in group C). Creatine kinase level elevation was higher in
      group C (p=0.03). CONCLUSION: Dexmedetomidine infusion before and after
      succinylcholine administration may be useful in diminishing the incidence of
      succinylcholine-induced myalgia in the early postoperative period. Routine use of
      dexmedetomidine cannot be recommended, but further research is needed with a
      larger number of patients.

PMID- 23552590
TI  - Glaucoma after open globe injury at a tertiary care university hospital in
      Central Saudi Arabia. Cumulative incidence and risk factors.
AB  - OBJECTIVE: To investigate the incidence and risk factors of glaucoma after open
      globe injury (OGI). METHODS: The medical records of all patients admitted with
      the diagnosis of OGI at the Department of Ophthalmology, King Abdulaziz
      University Hospital, Riyadh, Kingdom of Saudi Arabia and had undergone primary
      repair from January 1996 to December 2011 were retrospectively reviewed. RESULTS:
      For the 15-year study period, 775 patients who underwent repair of an OGI were
      identified. The overall risk of post-traumatic glaucoma was 5.3% (41/775) with a
      mean +/- SD follow-up period of 12+/-6.5 months. Univariate analysis revealed
      that Zone II injury (p=0.027), penetrating ocular injury (p=0.0008), lens injury
      (p=0.011), vitreous hemorrhage (p=0.002), and presence of intraocular foreign
      body (p<0.0001) were significantly associated with glaucoma. Age of more than 18
      years was critical (p=0.054). Following logistic regression, penetrating ocular
      injury (p=0.019), lens injury (p=0.002), and vitreous hemorrhage were significant
      (p=0.037). CONCLUSION: Glaucoma after OGI is not uncommon. Zone II injury,
      penetrating ocular injury, lens injury, presence of vitreous hemorrhage, and
      presence of an intraocular foreign body were significant risk factors for
      developing post-traumatic glaucoma.

PMID- 23552591
TI  - Causes of uveitis in a tertiary center in Western Saudi Arabia.
AB  - OBJECTIVE: To analyze the causes of uveitis and compare our results with national
      and international published studies. METHODS: This is a retrospective review of
      medical records of patients who attend the uveitic clinic of Magrabi Eye and Ear
      Hospital in Jeddah, Kingdom of Saudi Arabia from January 1999 to December 2011.
      RESULTS: We encountered 823 eyes of 587 uveitis patients (male: 319 [54%] and
      female: 268 [46%]). Native Saudi patients constituted 52% of our total
      population, expatriate Arabs 23%, and Afro-Asians 23%. Average age at
      presentation was 34.8+/-12.83 (range 5-70) years. Unilateral presentation was
      noted in 351 (60%) and bilateral in 236 (40%) patients. Idiopathic anterior
      uveitis was the most common diagnosis (n=268, 45.7%). Anterior uveitis was the
      most common anatomical diagnosis (n=335, 57.1%) followed by panuveitis (n=151,
      25.7%), posterior uveitis (n=51, 8.7%) and intermediate uveitis (n=50, 8.5%).
      There were 50 patients (8.5%) of Behcet's disease, 48 patients (8.2%) of Vogt
      Koyanagi-Harada disease (VKH) and 35 cases (6%) of toxoplasmosis. CONCLUSION: The
      most common cause of anatomic diagnosis was anterior uveitis. Behcet's disease
      was the most common identifiable cause of uveitis followed by VKH. The most
      common cause of infectious uveitis was toxoplasmosis. Idiopathic anterior uveitis
      was the most common uveitic entity.

PMID- 23552592
TI  - New method for evaluation of cervical vertebral maturation based on angular
      measurements.
AB  - OBJECTIVE: To investigate the validity of a new approach to assess the cervical
      vertebral maturation based on angular measurements of the lower border concavity
      of cervical vertebral bodies. METHODS: Hand-wrist and lateral cephalometric
      radiographs of 197 male subjects with age range of 10-15 years attending the
      orthodontic clinic at King Saud University, Riyadh, Kingdom of Saudi Arabia were
      utilized. The study was carried out between September 2009 and May 2011. The
      study sample was divided into 6 groups (group 1: 10 years to group 6: 15 years)
      based on the chronological age of the subject. The skeletal age of the subjects
      was determined using Greulich and Pyle's standard radiographic atlas, and
      skeletal maturation was assessed by Fishman's skeletal maturity indicators. The
      cervical vertebral maturation (CVM) of subjects was determined using angular
      measurements of the second, third, and fourth cervical vertebral bodies. The
      validity of the newly developed method was assessed by examining the correlation
      between CVM stages determined by the angular measurements and the skeletal
      maturation level as determined by the standard hand-wrist methods. RESULTS: A
      significant correlation (r=0.94) was found between the angular CVM stages and the
      skeletal age determined by Greulich and Pyle's atlas from hand-wrist radiographs.
      Also, a high correlation (r=0.94) was found between the angular CVM stages and
      the Fishman's hand-wrist skeletal maturity indicators. CONCLUSION: The new
      angular measurement approach to determine CVM is valid and has the potential to
      be applied in assessing skeletal maturity level in growing male children.

PMID- 23552593
TI  - Level of evidence of clinical orthopedic surgery research in Saudi Arabia.
AB  - OBJECTIVE: To evaluate the level of evidence (LOE) of Saudi clinical orthopedic
      research. METHODS: In July 2012, a list of Saudi orthopedic surgeons (N=93)
      affiliated with all major universities and hospitals in Saudi Arabia were
      obtained. PubMed and Embase searches were performed for all eligible studies over
      the last 2 decades (August 1991 to May 2012). The Oxford LOE scale was utilized
      to determine the LOE of these studies (Level V studies were excluded). The LOE
      trends were compared between the last 2 decades. In addition, the LOE of Saudi
      orthopedic studies was compared with North American studies. RESULTS: Of 251
      articles, 159 met the inclusion criteria for the LOE evaluation. Most of the
      published studies are Level IV (86%). The average level of evidence was 3.75.
      There was no statistically significant difference when we compared the LOE trend
      between the last 2 decades. North American studies contained higher proportions
      of high-level studies when compared to Saudi studies (p<0.05). CONCLUSION: Most
      of the published studies are low LOE. Academic staff, institutions, and training
      programs are required to develop research strategies to improve orthopedic
      research quality in Saudi Arabia.

PMID- 23552594
TI  - Prevalence of obesity among military personnel in Saudi Arabia and associated
      risk factors.
AB  - OBJECTIVE: To measure the prevalence of obesity among military personnel in the
      Kingdom of Saudi Arabia (KSA), and to identify its risk factors. METHODS: This
      nationwide cross-sectional study covered all 5 military regions of KSA. It
      included a multistage stratified random sample of 10,500 active military
      personnel. The World Health Organization STEP wise approach to chronic disease
      risk factor surveillance (STEPS) was used in the design of the data collection
      tool. The project lasted from January 2009 to February 2011. RESULTS: The
      response rate was 97.4%; 40.9% of the participants were overweight, 29% obese,
      and 42.4% had central obesity. Multivariate analysis revealed age, education
      years, and family history of diabetes or hypertension as statistically
      significant positive predictors of body mass index, while higher military rank,
      smoking, eating fruits more than twice per week, and heavy physical activities
      were negative predictors. CONCLUSION: Obesity is a major health problem among
      military personnel in this survey especially among soldiers, and is associated
      with unhealthy dietary and physical activity habits. Prompt action must be taken
      by the military medical services department in terms of intervention programs
      primarily directed to soldiers and overweight personnel to control obesity and
      mitigate its consequences. Review of the anthropometric standards for
      recruitment, continuation, and promotion in military service is recommended.

PMID- 23552595
TI  - Atomic force microscopy and tridimensional topography analysis of human enamel
      after resinous infiltration and storage in water.
AB  - OBJECTIVE: To evaluate the effect of water storage on surface roughness (Ra) of
      human enamel after treatment with resin infiltrant and fissure sealant, by
      utilizing atomic force microscopy (AFM) and microtomography. METHODS: This study
      was conducted after registration and ethical approval clarification at the
      College of Dentistry Research Center, King Saud University, Riyadh, Kingdom of
      Saudi Arabia between January 2011 and August 2011. Thirty enamel surface
      specimens were prepared from caries-free human premolar teeth. Specimens were
      divided into 3 groups: Group I, was the control; Group II, a resin infiltrant
      (Icon) was applied on the enamel surfaces; and Group III, the teeth were treated
      with fissure sealant (SealRite). All specimens were stored in distilled water for
      6 months and then, subjected to AFM Veeco CP11 1.2 analysis. A few specimens were
      scanned by skyscan-1072-x-ray microtomography. The Ra mean readings were recorded
      and statistical analysis was performed with the Statistical Package for Social
      Sciences Version 16 at the significance level of p<0.05. RESULTS: No significant
      differences in the mean Ra were recorded among the 3 groups, (Group I = 0.21+/
      0.057), (Group II = 0.23+/-0.075), and (Group III = 0.20+/-0.039) at p=0.747. The
      AFM images of enamel surface show thin and inhomogeneous Icon resin in Group II,
      meanwhile, the SealRite in Group III showed a homogeneous layer in all specimens.
      The microtomography supported the findings of the AFM images. CONCLUSION: The
      persistence of the SealRite in all specimens revealed its low solubility in water
      and its protective effect on enamel surface.

PMID- 23552596
TI  - Reduced systemic inflammatory mediators after treatment of chronic gingivitis.
AB  - OBJECTIVE: To assess the changes in the level of C-reactive protein (CRP) and
      tumor necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid (GCF) after
      treatment of chronic gingivitis in systemically healthy individuals. METHODS:
      This is a clinical trial conducted at Case Western Reserve University, Cleveland,
      Ohio, United States of America from February to December 2011. A total of 41
      systemically healthy subjects were assigned to 2 groups according to the severity
      of gingival inflammation. Group I consisted of 18 subjects who had mild gingival
      inflammation; and group II consisted of 23 with more severe gingival
      inflammation. Periodontal assessment consisted of gingival index (GI), probing
      depths (PD), and GCF volume. Four to six weeks after prophylaxis and oral hygiene
      instruction, the same measurements were repeated. The level of CRP and TNF-alpha
      in the GCF was determined using enzyme-linked immunosorbent assays. RESULTS: A
      statistically significant reduction in the mean CRP and TNF-alpha levels after
      the treatment was found in the severe, but not in the mild gingivitis group. Both
      groups showed a statistically significant reduction in GI, PD, and periotron
      readings after the treatment. CONCLUSION: Treatment of severe chronic gingivitis
      reduces the levels of CRP and TNF-alpha in GCF of otherwise systemically healthy
      individuals, which could have an impact on preventing or controlling future or
      existing systemic disease conditions.

PMID- 23552597
TI  - Aspirin induced leukocytoclastic vasculitis, lower gastrointestinal hemorrhage
      and acute renal failure (mimicking systemic vasculitis).
AB  - This is a case of a 60-year-old gentleman who presented with an extensive
      cutaneous vasculitic rash (leukocytoclastic) with lower gastrointestinal bleeding
      following a small dose of aspirin (81 mg). The aspirin was stopped immediately.
      Three weeks later, he had acute renal failure, which was initially thought to be
      secondary to systemic vasculitis, but proved to be acute renal tubular necrosis
      as a delayed reaction to aspirin.

PMID- 23552598
TI  - Oral rehabilitation of a case of Papillon-Lefevre syndrome with dental implants.
AB  - Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder
      characterized by diffuse palmoplantar keratoderma and precocious aggressively
      progressing periodontitis, leading to the premature loss of deciduous and
      permanent teeth. Full mouth rehabilitation with implant supported fixed
      prosthesis provides numerous advantages over the conventional denture in terms of
      esthetics, function, longevity of the prosthesis, and patient satisfaction. We
      report a case of PLS in a 19-year-old female who underwent extraction of all the
      teeth followed by full mouth rehabilitation with implant supported fixed
      prostheses. A one-year follow up of the case showed functionally and esthetically
      stable dental implant with no signs of infection or bone loss.

PMID- 23552599
TI  - Analysis of factors related to patient peritoneal dialysis drop out rates.

PMID- 23552600
TI  - Serum vitamins A and E deficiencies in patients with inflammatory bowel disease.

PMID- 23552601
TI  - Yarning about health checks: barriers and enablers in an urban Aboriginal medical
      service.
AB  - The annual health check for Aboriginal and Torres Strait Islander People has been
      welcomed as a means of conducting a comprehensive assessment to address
      preventive health care delivery, identify new diagnoses and initiate new
      treatments. Rates of health check uptake across Australia have been poor with
      less than 12% of the eligible population receiving one during 2009/10. This
      qualitative study sought to identify barriers and enablers to undertaking health
      checks in an urban Aboriginal Medical Service through semistructured interviews
      with 25 clinical staff (doctors, nurses and Aboriginal and Torres Strait Islander
      health workers). Clinical systems for conducting health checks were unclear to
      staff, with barriers relating to time pressures for both patients and clinic
      staff, and lack of clarity about staff responsibilities for initiating and
      conducting the health check. Additionally some staff perceived some content as
      sensitive, invasive, culturally inappropriate and of questionable value. Other
      barriers included concerns about community health literacy, disengagement with
      preventative health care, and suspicion about confidentiality and privacy. The
      development of clear service-wide systems that support the conduct of health
      checks are required to increase uptake, combined with supportive local clinical
      leadership and audit and feedback systems. Staff training, consideration of
      culture and roles, and critical review of health check content may improve staff
      confidence and community acceptance. Community-based health education and
      promotion is strongly supported by staff to increase client engagement, knowledge
      and acceptance of the health check. 

PMID- 23552602
TI  - Selection of a highly invasive neuroblastoma cell population through long-term
      human cytomegalovirus infection.
AB  - The human cytomegalovirus (HCMV) is suspected to increase tumour malignancy by
      infection of cancer and/or stroma cells (oncomodulation). So far, oncomodulatory
      mechanisms have been attributed to the presence of HCMV and direct action of its
      gene products on cancer cells. Here, we investigated whether the prolonged
      presence of HCMV can result in the irreversible selection of a cancer cell
      population with increased malignancy. The neuroblastoma cell line UKF-NB-4 was
      long-term (200 passages) infected with the HCMV strain Hi91 (UKF-NB-4(Hi)) before
      virus eradication using ganciclovir (UKF-NB-4(HiGCV)). Global gene expression
      profiling of UKF-NB-4, UKF-NB-4(Hi) and UKF-NB-4(HiGCV) cells and subsequent
      bioinformatic signal transduction pathway analysis revealed clear differences
      between UKF-NB-4 and UKF-NB-4(Hi), as well as between UKF-NB-4 and UKF-NB
      4(HiGCV) cells, but only minor differences between UKF-NB-4(Hi) and UKF-NB
      4(HiGCV) cells. Investigation of the expression of a subset of five genes in
      different chronically HCMV-infected cell lines before and after virus eradication
      suggested that long-term HCMV infection reproducibly causes specific changes.
      Array comparative genomic hybridisation showed virtually the same genomic
      differences for the comparisons UKF-NB-4(Hi)/UKF-NB-4 and UKF-NB-4(HiGCV)/UKF-NB
      4. UKF-NB-4(Hi) cells are characterised by an increased invasive potential
      compared with UKF-NB-4 cells. This phenotype was completely retained in UKF-NB
      4(HiGCV) cells. Moreover, there was a substantial overlap in the signal
      transduction pathways that differed significantly between UKF-NB-4(Hi)/UKF-NB
      4(HiGCV) and UKF-NB-4 cells and those differentially regulated between tumour
      tissues from neuroblastoma patients with favourable or poor outcome. In
      conclusion, we present the first experimental evidence that long-term HCMV
      infection can result in the selection of tumour cell populations with enhanced
      malignancy.

PMID- 23552603
TI  - COX-2/PGE2: molecular ambassadors of Kaposi's sarcoma-associated herpes virus
      oncoprotein-v-FLIP.
AB  - Kaposi's sarcoma herpesvirus (KSHV) latent oncoprotein viral FLICE (FADD-like
      interferon converting enzyme)-like inhibitory protein (v-FLIP) or K13, a potent
      activator of NF-kappaB, has well-established roles in KSHV latency and
      oncogenesis. KSHV-induced COX-2 represents a novel strategy employed by KSHV to
      promote latency and inflammation/angiogenesis/invasion. Here, we demonstrate that
      v-FLIP/K13 promotes tumorigenic effects via the induction of host protein COX-2
      and its inflammatory metabolite PGE2 in an NF-kappaB-dependent manner. In
      addition to our previous studies demonstrating COX-2/PGE2's role in
      transcriptional regulation of KSHV latency promoter and latent gene expression,
      the current study adds to the complexity that though LANA-1 (latency associated
      nuclear antigen) is utilizing COX-2/PGE2 as critical factors for its
      transcriptional regulation, it is the v-FLIP/K13 gene in the KSHV latency cluster
      that maintains continuous COX-2/PGE2 levels in the infected cells. We demonstrate
      that COX-2 inhibition, via its chemical inhibitors (NS-398 or celecoxib), reduced
      v-FLIP/K13-mediated NF-kappaB induction, and extracellular matrix (ECM)
      interaction-mediated signaling, mitochondrial antioxidant enzyme manganese
      superoxide dismutase (MnSOD) levels, and subsequently downregulated detachment
      induced apoptosis (anoikis) resistance. vFLIP expression mediated the secretion
      of cytokines, and spindle cell differentiation activated the phosphorylation of
      p38, RSK, FAK, Src, Akt and Rac1-GTPase. The COX-2 inhibition in v-FLIP/K13
      HMVECs reduced inflammation and invasion/metastasis-related genes, along with
      reduced anchorage-independent colony formation via modulating 'extrinsic' as well
      as 'intrinsic' cell death pathways. COX-2 blockade in v-FLIP/K13-HMVEC cells
      drastically augmented cell death induced by removal of essential growth/survival
      factors secreted in the microenvironment. Transformed cells obtained from
      anchorage-independent colonies of COX-2 inhibitor-treated v-FLIP/K13-HMVEC cells
      expressed lower levels of endothelial-mesenchymal transition genes such as slug,
      snail and twist, and higher expression of the tumor-suppressor gene, E-cadherin.
      Taken together, our study provides strong evidences that FDA-approved COX-2
      inhibitors have great potential in blocking tumorigenic events linked to KSHV's
      oncogenic protein v-FLIP/K13.

PMID- 23552604
TI  - The CEACAM1 tumor suppressor is an ATM and p53-regulated gene required for the
      induction of cellular senescence by DNA damage.
AB  - The p53 tumor-suppressor protein has a key role in the induction of cellular
      senescence, an important barrier to cancer development. However, very little is
      known about the physiological mediators of cellular senescence induced by p53.
      CEACAM1 is an immunoglobulin superfamily member whose expression is frequently
      lost in human tumors and exhibits tumor-suppressor features in several
      experimental systems, including Ceacam1 knockout mice. There is currently little
      understanding of the pathways and mechanisms by which CEACAM1 exerts its tumor
      suppressor function. Here we report that CEACAM1 is strongly upregulated during
      the cellular response to DNA double-strand breaks (DSBs) starting from the lowest
      doses of DSB inducers used, and that upregulation is mediated by the ataxia
      telangiectasia mutated (ATM)/p53 pathway. Stable silencing of CEACAM1 showed that
      CEACAM1 is required for p53-mediated cellular senescence, but not initial cell
      growth arrest, in response to DNA damage. These findings identify CEACAM1 as a
      key component of the ATM/p53-mediated cellular response to DNA damage, and as a
      tumor suppressor mediating cellular senescence downstream of p53.

PMID- 23552605
TI  - IKKbeta-I-kappaBE-c-Rel/p50: a new axis of NF-kappaB activation in lung
      epithelial cells.
AB  - Cigarette smoke (CS), a major risk factor for developing lung cancer, is known to
      activate transcriptional activator nuclear factor kappa B (NF-kappaB). However,
      the underlying mechanism of this activation remains unclear because of
      conflicting reports. As NF-kappaB has a pivotal role in the generation and
      maintenance of malignancies, efforts were targeted towards understanding its
      activation mechanism using both ex vivo and in vivo studies. The results show
      that CS-induced NF-kappaB activation mechanism is different from that of other
      pro-inflammatory signals such as lipopolysaccharide (LPS). The NF-kappaB dimer
      that translocates to the nucleus upon stimulation with CS is predominantly
      composed of c-Rel/p50 and this translocation involves degradation of I-kappaBE
      and not I-kappaBalpha. This degradation of I-kappaBE depends on IKKbeta activity,
      which preferentially targets I-kappaBE. Consistently, CS-activated form of
      IKKbeta was found to be different from that involved in LPS activation as neither
      Ser177 nor Ser181 of IKKbeta is crucial for CS-induced NF-kappaB activation.
      Thus, unlike other pro-inflammatory stimulations where p65 and I-kappaBalpha have
      a central role, the predominantly active signaling cascade in CS-induced NF
      kappaB activation in the lung epithelial cells comprises of IKKbeta-I-kappaBE-c
      Rel/p50. Thus, this study uncovers a new axis of NF-kappaB activation wherein I
      kappaBE and c-Rel have the central role.

PMID- 23552606
TI  - Histopathologic changes in punctal stenosis.
AB  - PURPOSE: To describe the pathologic changes in punctal stenosis by reporting the
      histopathologic findings in a series of punctoplasty specimens. METHODS:
      Observational retrospective chart review. Electronic health records of all
      patients having punctoplasty over a 2-year period at an academic oculoplastic
      practice were examined. All patients whose records included pathology reports
      were entered into a database. RESULTS: Twenty-four patients, representing 30
      eyes, had pathology records in the electronic health records. Patients were 75%
      women and had an average age of 65 (19-88) years. Associated conditions included
      blepharitis (71%), dry eye syndrome, or Meibomian gland dysfunction (63%).
      Histopathologic examination demonstrated chronic inflammation in 11 eyes (36.7%),
      fibrosis in 7 eyes (23.3%), chronic inflammation and fibrosis in 4 eyes (13.3%),
      squamous metaplasia in 3 eyes (10%), normal conjunctival mucosa in 3 eyes (10%),
      and Actinomyces israelii canaliculitis in 2 eyes (6.7%). CONCLUSIONS: Nearly all
      histopathologic specimens revealed findings consistent with inflammation,
      fibrosis, or both. These findings provide evidence to support the hypothesis that
      the many etiologic causes of punctal stenosis are linked by a common
      pathophysiologic mechanism involving inflammation.

PMID- 23552607
TI  - Comparison of preferences between onabotulinumtoxinA (Botox) and
      incobotulinumtoxinA (Xeomin) in the treatment of benign essential blepharospasm.
AB  - PURPOSE: To evaluate subjective outcomes and preferences in patients with benign
      essential blepharospasm (BEB) treated with both onabotulinumtoxinA (Botox) and
      incobotulinumtoxinA (Xeomin). METHODS: An institutional review board approved
      retrospective review of 128 patients treated with onabotulinumtoxinA for BEB by 1
      author (J.B.H.). Fifty of these patients were switched to incobotulinumtoxinA as
      an alternate drug. At scheduled follow up, patients decided to continue with
      incobotulinumtoxinA or switch to onabotulinumtoxinA. Patient preferences
      regarding treatment with onabotulinumtoxinA versus incobotulinumtoxinA were
      recorded. The preference groups were analyzed using unpaired Student t test, with
      statistical significance set at p < 0.05. RESULTS: Of the 50 incobotulinumtoxinA
      patients, the mean age was 64.9 years; 39 (78%) were women and 11 (22%) were men.
      In all, 26 (52%) preferred incobotulinumtoxinA and 24 (48%) preferred
      onabotulinumtoxinA. Most frequently, those who preferred incobotulinumtoxinA
      believed that it was "more effective" (N = 10, 29%), whereas those who preferred
      onabotulinumtoxinA concluded that it had a "longer duration" (N = 11, 37%). The
      mean treatment interval was 13.0 weeks (standard deviation [SD] = 6.39) in those
      who preferred onabotulinumtoxinA, whereas it was 10.2 weeks (SD = 2.15) in those
      who preferred incobotulinumtoxinA (p = 0.017). There was no statistical
      difference when comparing mean disease duration, number of total treatments, and
      number of units/treatment between the 2 preference groups. CONCLUSIONS: This
      study demonstrates that patients who prefer incobotulinumtoxinA over
      onabotulinumtoxinA had a statistically significant shorter treatment interval. In
      addition, those who preferred incobotulinumtoxinA thought it was more effective,
      whereas those patients who preferred onabotulinumtoxinA thought it had a longer
      duration. This information can be used when counseling both newly diagnosed and
      long-standing BEB patients regarding their therapeutic options.

PMID- 23552608
TI  - Bilobed flap in the reconstruction of inferior and/or lateral periorbital
      defects.
AB  - PURPOSE: To report the outcome of bilobed flap (BF) reconstruction of inferior
      and/or lateral periorbital defects following tumor excision. METHODS: Records of
      20 patients who underwent inferior and/or lateral periorbital reconstruction with
      the BF were reviewed. The surgery was performed with local anesthesia in 18
      patients and with general anesthesia in 2. Malignant tumors were excised together
      with a 4- to 5-mm margin of surrounding skin. Superolaterally based BFs were
      created from the malar or zygomatic region to cover the defects. RESULTS:
      Patients ranged in age from 48 to 86 years (mean, 67 years). Nineteen patients
      had epithelial carcinoma and 1 had pilomatrixoma. Mean tumor diameter was 16 mm
      (range, 7-42 mm). Skin defects were located in the inferior (n = 14), lateral (n
      = 4), or inferolateral (n = 2) periorbital region. The BF was used in combination
      with the posterior lamella and/or canthus reconstruction techniques in 9
      patients. For skin defects, BF was used alone in 17 patients, together with other
      flaps in 3. Primary closure of the skin defect with the flaps was achieved in 19
      patients (95%). Three patients (15%) developed major complications requiring
      revision surgery (2 canthal webbings, 1 permanent pin-cushion deformity, and 1
      ptosis) and 6 patients developed minor temporary complications. Mean follow-up
      duration was 34 months (range, 9-75 months). CONCLUSIONS: The BF is a valuable
      alternative for reconstruction of inferior and/or lateral periorbital defects
      alone or in combination with other eyelid reconstruction methods to achieve good
      functional and aesthetic outcome.

PMID- 23552609
TI  - Orbital cavitary rhabdomyosarcoma: case report and literature review.
AB  - Orbital cavitary rhabdomyosarcoma has been previously reported in 2 cases. The
      case presented here was a 15-year-old boy who had proptosis, pain, periorbital
      hyperemia, and visual loss in his OD, which progressed in 6 weeks. Radiologic
      studies demonstrated a well-demarcated, multilobulated, large mass with cavities,
      extending from the anterior orbit to the apex, suggesting a diagnosis of
      venolymphatic malformation with an intrinsic hemorrhage. On surgery, a
      multilobular, hemorrhagic cystic mass was almost completely excised. Histologic
      examination revealed a diagnosis of embryonal rhabdomyosarcoma. After
      postoperative chemotherapy and radiotherapy, the tumor did not recur during a
      follow-up period of 45 months. This case, together with the previous ones,
      suggests that cavitary orbital rhabdomyosarcomas may have some distinct clinical,
      radiologic, and surgical characteristics. 

PMID- 23552610
TI  - Comparison of psychotherapies for adult depression to pill placebo control
      groups: a meta-analysis.
AB  - BACKGROUND: The effects of antidepressants for treating depressive disorders have
      been overestimated because of selective publication of positive trials.
      Reanalyses that include unpublished trials have yielded reduced effect sizes.
      This in turn has led to claims that antidepressants have clinically insignificant
      advantages over placebo and that psychotherapy is therefore a better alternative.
      To test this, we conducted a meta-analysis of studies comparing psychotherapy
      with pill placebo. METHOD: Ten 10 studies comparing psychotherapies with pill
      placebo were identified. In total, 1240 patients were included in these studies.
      For each study, Hedges' g was calculated. Characteristics of the studies were
      extracted for subgroup and meta-regression analyses. RESULTS: The effect of
      psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence
      interval (CI) 0.14-0.36, I2 = 0%, 95% CI 0-58]. This effect size corresponds to a
      number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy
      conditions scored 2.66 points lower on the Hamilton Depression Rating Scale
      (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression
      Inventory (BDI). Some indications for publication bias were found (two missing
      studies). We found no significant differences between subgroups of the studies
      and in meta-regression analyses we found no significant association between
      baseline severity and effect size. CONCLUSIONS: Although there are differences
      between the role of placebo in psychotherapy and pharmacotherapy research,
      psychotherapy has an effect size that is comparable to that of antidepressant
      medications. Whether these effects should be deemed clinically relevant remains
      open to debate.

PMID- 23552611
TI  - The inferior vena cava filter: how could a medical device be so well accepted
      without any evidence of efficacy?

PMID- 23552612
TI  - Proteomic analysis of plasma after branched chain enriched mixture
      supplementation in mice.
AB  - BACKGROUND: Branched chain amino acid (BCAA) supplementation is a recently
      identified strategy to promote longevity in mice. A proteomic approach was used
      to identify proteins which are differentially expressed in the sera of mice
      following supplementation with selected branched chain amino acid enriched
      mixture (BCAAem). FINDINGS: 12 male mice (C57Bl6, 9 months-old) were randomly
      assigned to unsupplemented (Control, n = 6) and supplemented (BCAA, n = 6, 0.1
      mg/gr/day in drink water for 4 weeks). At the end of treatment total plasma
      samples from Control and BCAAem mice were separated by two-dimensional gel
      electrophoresis (2-DE). After staining, the gels were imaged and differential
      protein expression patterns were interrogated using image analysis software.
      Spots showing a different expression level were identified through a comparison
      with 2D maps found in databases officially recognized (ExPASy).Master gels of
      Control and BCAA mice exhibited slightly different 2-DE patterns as only 10 spots
      out of 500 appeared differentially expressed: 8 were upregulated (corresponding
      to Apolipoprotein A-I (APOA1), Complement factor B, Complement C3, Immunoglobulin
      light chain) and 2 appeared downregulated (Alpha-1-antitrypsin and unknown).
      CONCLUSIONS: Supplementation with BCAAem in mice results in a slight perturbation
      of the host serum proteome. Of particular interest is the increased
      Apolipoprotein A-I (APOAI) following treatment.

PMID- 23552613
TI  - Overcoming the shortcomings of the Nernst-Planck model.
AB  - This is a study on electrolytes that takes a thermodynamically consistent
      coupling between mechanics and diffusion into account. It removes some inherent
      deficiencies of the popular Nernst-Planck model. A boundary problem for
      equilibrium processes is used to illustrate the features of the new model.

PMID- 23552614
TI  - Spiral computed tomography phase-space source model in the BEAMnrc/EGSnrc Monte
      Carlo system: implementation and validation.
AB  - Currently, the BEAMnrc/EGSnrc Monte Carlo (MC) system does not provide a spiral
      CT source model for the simulation of spiral CT scanning. We developed and
      validated a spiral CT phase-space source model in the BEAMnrc/EGSnrc system. The
      spiral phase-space source model was implemented in the DOSXYZnrc user code of the
      BEAMnrc/EGSnrc system by analyzing the geometry of spiral CT scan-scan range,
      initial angle, rotational direction, pitch, slice thickness, etc. Table movement
      was simulated by changing the coordinates of the isocenter as a function of beam
      angles. Some parameters such as pitch, slice thickness and translation per
      rotation were also incorporated into the model to make the new phase-space source
      model, designed specifically for spiral CT scan simulations. The source model was
      hard-coded by modifying the 'ISource = 8: Phase-Space Source Incident from
      Multiple Directions' in the srcxyznrc.mortran and dosxyznrc.mortran files in the
      DOSXYZnrc user code. In order to verify the implementation, spiral CT scans were
      simulated in a CT dose index phantom using the validated x-ray tube model of a
      commercial CT simulator for both the original multi-direction source (ISOURCE =
      8) and the new phase-space source model in the DOSXYZnrc system. Then the
      acquired 2D and 3D dose distributions were analyzed with respect to the input
      parameters for various pitch values. In addition, surface-dose profiles were also
      measured for a patient CT scan protocol using radiochromic film and were compared
      with the MC simulations. The new phase-space source model was found to simulate
      the spiral CT scanning in a single simulation run accurately. It also produced
      the equivalent dose distribution of the ISOURCE = 8 model for the same CT scan
      parameters. The MC-simulated surface profiles were well matched to the film
      measurement overall within 10%. The new spiral CT phase-space source model was
      implemented in the BEAMnrc/EGSnrc system. This work will be beneficial in
      estimating the spiral CT scan dose in the BEAMnrc/EGSnrc system.

PMID- 23552615
TI  - Automated detection and quantification of granular cell compartments.
AB  - Many cellular processes are organized in a compartmentalized and dynamic fashion
      to ensure effective adaptation to physiological changes. Thus, in response to
      stress and disease, cells initiate protective mechanisms to restore homeostasis.
      Among these mechanisms are the arrest of translation and remodeling of
      ribonucleoprotein complexes into granular compartments in the cytoplasm, known as
      stress granules (SGs). To date, the analysis of SGs has relied on the manual
      demarcation and measurement of the compartment, making quantitative studies time
      consuming, while preventing the efficient use of high-throughput technology. We
      developed the first fully automated, computer-based procedures that measure the
      association of fluorescent molecules with granular compartments. Our methods
      quantify automatically multiple granule parameters and generate data at the level
      of single cells or individual SGs. These techniques detect simultaneously in an
      automated fashion proteins and RNAs located in SGs. The effectiveness of our
      protocols is demonstrated by studies that reveal several of the unique biological
      and structural characteristics of SGs. In particular, we show that the type of
      stress determines granule size and composition, as illustrated by the
      concentration of poly(A)-RNA and a specific SG marker protein. Furthermore, we
      took advantage of the computer-based and automated methods to design assays
      suitable for high-throughput screening.

PMID- 23552616
TI  - From the street to the laboratory: analytical profiles of methoxetamine, 3
      methoxyeticyclidine and 3-methoxyphencyclidine and their determination in three
      biological matrices.
AB  - Three psychoactive arylcyclohexylamines, advertised as "research chemicals," were
      obtained from an online retailer and characterized by gas chromatography ion trap
      electron and chemical ionization mass spectrometry, nuclear magnetic resonance
      spectroscopy and diode array detection. The three phencyclidines were identified
      as 2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone (methoxetamine), N-ethyl-1-(3
      methoxyphenyl)cyclohexanamine and 1-[1-(3-methoxyphenyl)cyclohexyl]piperidine. A
      qualitative/quantitative method of analysis was developed and validated using
      liquid chromatography (HPLC) electrospray tandem mass spectrometry and
      ultraviolet (UV) detection for the determination of these compounds in blood,
      urine and vitreous humor. HPLC-UV proved to be a robust, accurate and precise
      method for the qualitative and quantitative analysis of these substances in
      biological fluids (0.16-5.0 mg/L), whereas the mass spectrometer was useful as a
      confirmatory tool.

PMID- 23552617
TI  - A new type of metal chelate affinity chromatography using trivalent lanthanide
      ions for phosphopeptide enrichment.
AB  - In this study, a new type of immobilized metal-ion affinity chromatography (IMAC)
      resin for the isolation of phosphopeptides was synthesized which is based on the
      specific interaction between phosphate groups and chelated lanthanide metal ions.
      In this regard trivalent lanthanum, holmium and erbium ions were chelated to a
      highly porous phosphonate polymer which was prepared by radical polymerization of
      vinylphosphonic acid (VPA) and divinylbenzene (DVB). The developed method was
      evaluated with peptide mixtures from digested standard proteins (alpha-casein,
      beta-casein and ovalbumin) as well as with bovine milk, egg white and a spiked
      HeLa cell lysate. Compared to the commonly used TiO2 approach, the presented
      method showed higher selectivity for phosphorylated peptides. This can be
      explained by the strong preference of trivalent lanthanide ions for phosphates
      with which they form very tight ionic bonds. Mono- and multiply phosphorylated
      peptides could be enriched and released in a single basic elution step, while non
      phosphorylated peptides remained on the resin. Ab initio quantum mechanical
      energy minimizations of model complexes for polymer-ion-ligand interactions
      provided geometries, binding energies and charges which are discussed in
      conjunction with the observed experimental properties, leading to the most
      satisfying agreement. The presented lanthanide-IMAC resins represent promising
      affinity materials for the selective isolation of phosphopeptides from biological
      samples.

PMID- 23552619
TI  - ACP Journal Club. Aspirin did not reduce recurrence after a first-ever,
      unprovoked venous thromboembolism.

PMID- 23552620
TI  - Multiple epithelioid Spitz nevi or tumors with loss of BAP1 expression: a clue to
      a hereditary tumor syndrome.
AB  - IMPORTANCE: Recently, a group of melanocytic tumors with loss of BAP1 expression
      has been described. The lesions may occur sporadically or as part of a familial
      cancer syndrome. They have distinct histopathologic features characterized by a
      nevus like silhouette and cytologic composition of large epithelioid melanocytes
      with oval vesicular nuclei, distinct nucleoli, and abundant cytoplasm. The large
      melanocytes are immunohistochemically characterized by loss of nuclear labeling
      for BAP1. OBSERVATIONS: We describe a 21-year-old patient with multiple combined
      melanocytic proliferations composed of both a nevus component with strong BAP1
      expression and a large epithelioid melanocyte population with loss of BAP1
      expression. The occurrence of multiple BAP1 loss melanocytic lesions raised
      concerns about a possible germline mutation. Sequence analysis of DNA from
      lesional and nonlesional skin confirmed a BAP1 germline mutation. CONCLUSIONS AND
      RELEVANCE: The presence of multiple clinically banal-appearing melanocytic
      lesions with childhood onset suggests that the combined lesions with BAP1 loss
      large epithelioid melanocytes described herein are probably combined nevi. Our
      findings also illustrate how the detection of a histopathologically distinct
      melanocytic lesion, coupled with knowledge of its possible association with a
      hereditary tumor syndrome, can lead to the suspicion and confirmation of a
      germline mutation.

PMID- 23552621
TI  - Differential freshwater flagellate community response to bacterial food quality
      with a focus on Limnohabitans bacteria.
AB  - Different bacterial strains can have different value as food for heterotrophic
      nanoflagellates (HNF), thus modulating HNF growth and community composition. We
      examined the influence of prey food quality using four Limnohabitans strains, one
      Polynucleobacter strain and one freshwater actinobacterial strain on growth
      (growth rate, length of lag phase and growth efficiency) and community
      composition of a natural HNF community from a freshwater reservoir.
      Pyrosequencing of eukaryotic small subunit rRNA amplicons was used to assess time
      course changes in HNF community composition. All four Limnohabitans strains and
      the Polynucleobacter strain yielded significant HNF community growth while the
      actinobacterial strain did not although it was detected in HNF food vacuoles.
      Notably, even within the Limnohabitans strains we found significant prey-related
      differences in HNF growth parameters, which could not be related only to size of
      the bacterial prey. Sequence data characterizing the HNF communities showed also
      that different bacterial prey items induced highly significant differences in
      community composition of flagellates. Generally, Stramenopiles dominated the
      communities and phylotypes closely related to Pedospumella (Chrysophyceae) were
      most abundant bacterivorous flagellates rapidly reacting to addition of the
      bacterial prey of high food quality. 

PMID- 23552622
TI  - Effects of environmental variation and spatial distance on bacteria, archaea and
      viruses in sub-polar and arctic waters.
AB  - We investigated the influence of environmental parameters and spatial distance on
      bacterial, archaeal and viral community composition from 13 sites along a 3200-km
      long voyage from Halifax to Kugluktuk (Canada) through the Labrador Sea, Baffin
      Bay and the Arctic Archipelago. Variation partitioning was used to disentangle
      the effects of environmental parameters, spatial distance and spatially
      correlated environmental parameters on prokaryotic and viral communities. Viral
      and prokaryotic community composition were related in the Labrador Sea, but were
      independent of each other in Baffin Bay and the Arctic Archipelago. In oceans,
      the dominant dispersal mechanism for prokaryotes and viruses is the movement of
      water masses, thus, dispersal for both groups is passive and similar.
      Nevertheless, spatial distance explained 7-19% of the variation in viral
      community composition in the Arctic Archipelago, but was not a significant
      predictor of bacterial or archaeal community composition in either sampling area,
      suggesting a decoupling of the processes regulating community composition within
      these taxonomic groups. According to the metacommunity theory, patterns in
      bacterial and archaeal community composition suggest a role for species sorting,
      while patterns of virus community composition are consistent with species sorting
      in the Labrador Sea and suggest a potential role of mass effects in the Arctic
      Archipelago. Given that, a specific prokaryotic taxon may be infected by multiple
      viruses with high reproductive potential, our results suggest that viral
      community composition was subject to a high turnover relative to prokaryotic
      community composition in the Arctic Archipelago. 

PMID- 23552623
TI  - The dynamic bacterial communities of a melting High Arctic glacier snowpack.
AB  - Snow environments can occupy over a third of land surface area, but little is
      known about the dynamics of snowpack bacteria. The effect of snow melt on
      bacterial community structure and diversity of surface environments of a Svalbard
      glacier was examined using analyses of 16S rRNA genes via T-RFLP, qPCR and 454
      pyrosequencing. Distinct community structures were found in different habitat
      types, with changes over 1 week apparent, in particular for the dominant
      bacterial class present, Betaproteobacteria. The differences observed were
      consistent with influences from depositional mode (snowfall vs aeolian dusts),
      contrasting snow with dust-rich snow layers and near-surface ice. Contrary to
      that, slush as the decompositional product of snow harboured distinct lineages of
      bacteria, further implying post-depositional changes in community structure. Taxa
      affiliated to the betaproteobacterial genus Polaromonas were particularly
      dynamic, and evidence for the presence of betaproteobacterial ammonia-oxidizing
      bacteria was uncovered, inviting the prospect that the dynamic bacterial
      communities associated with snowpacks may be active in supraglacial nitrogen
      cycling and capable of rapid responses to changes induced by snowmelt.
      Furthermore the potential of supraglacial snowpack ecosystems to respond to
      transient yet spatially extensive melting episodes such as that observed across
      most of Greenland's ice sheet in 2012 merits further investigation. 

PMID- 23552624
TI  - Diatom assemblages promote ice formation in large lakes.
AB  - We present evidence for the directed formation of ice by planktonic communities
      dominated by filamentous diatoms sampled from the ice-covered Laurentian Great
      Lakes. We hypothesize that ice formation promotes attachment of these non-motile
      phytoplankton to overlying ice, thereby maintaining a favorable position for the
      diatoms in the photic zone. However, it is unclear whether the diatoms themselves
      are responsible for ice nucleation. Scanning electron microscopy revealed
      associations of bacterial epiphytes with the dominant diatoms of the
      phytoplankton assemblage, and bacteria isolated from the phytoplankton showed
      elevated temperatures of crystallization (T(c)) as high as -3  degrees C. Ice
      nucleation-active bacteria were identified as belonging to the genus Pseudomonas,
      but we could not demonstrate that they were sufficiently abundant to incite the
      observed freezing. Regardless of the source of ice nucleation activity, the
      resulting production of frazil ice may provide a means for the diatoms to be
      recruited to the overlying lake ice, thereby increasing their fitness. Bacterial
      epiphytes are likewise expected to benefit from their association with the
      diatoms as recipients of organic carbon excreted by their hosts. This novel
      mechanism illuminates a previously undescribed stage of the life cycle of the
      meroplanktonic diatoms that bloom in Lake Erie and other Great Lakes during
      winter and offers a model relevant to aquatic ecosystems having seasonal ice
      cover around the world.

PMID- 23552625
TI  - Temporal variability in soil microbial communities across land-use types.
AB  - Although numerous studies have investigated changes in soil microbial communities
      across space, questions about the temporal variability in these communities and
      how this variability compares across soils have received far less attention. We
      collected soils on a monthly basis (May to November) from replicated plots
      representing three land-use types (conventional and reduced-input row crop
      agricultural plots and early successional grasslands) maintained at a research
      site in Michigan, USA. Using barcoded pyrosequencing of the 16S rRNA gene, we
      found that the agricultural and early successional land uses harbored unique soil
      bacterial communities that exhibited distinct temporal patterns. alpha-Diversity,
      the numbers of taxa or lineages, was significantly influenced by the sampling
      month with the temporal variability in alpha-diversity exceeding the variability
      between land-use types. In contrast, differences in community composition across
      land-use types were reasonably constant across the 7-month period, suggesting
      that the time of sampling is less important when assessing beta-diversity
      patterns. Communities in the agricultural soils were most variable over time and
      the changes were significantly correlated with soil moisture and temperature.
      Temporal shifts in bacterial community composition within the successional
      grassland plots were less predictable and are likely a product of complex
      interactions between the soil environment and the more diverse plant community.
      Temporal variability needs to be carefully assessed when comparing microbial
      diversity across soil types and the temporal patterns in microbial community
      structure can not necessarily be generalized across land uses, even if those
      soils are exposed to the same climatic conditions. 

PMID- 23552626
TI  - Troponin I, but not BNP, is associated with phosphorus, calcium and vitamin D in
      stable coronary artery disease.
AB  - BACKGROUND: Elevated plasma cardiac troponin, elevated plasma phosphorus and
      decreased plasma vitamin D have been shown to be associated with negative
      outcomes. METHODS AND RESULTS: Troponin I, calcium, phosphorus and 25-OH vitamin
      D were studied in a cohort of 60 patients with stable coronary heart disease and
      preserved left ventricular function. Using a cut-off value of 0.012 ng/mL for
      plasma troponin I, patients with higher values (18 patients), when compared to
      the other patients (n=42), had higher mean values for plasma phosphorus
      (3.42+0.45 mg/dL vs 3.17+0.45 mg/dL, p= 0.041) and calcium (5.08+0.23 mEq/L vs
      4.92+0.18 mEq/L, p= 0.016) and lower values for 25-OH vitamin D (14.2+5.6 ng/mL
      vs 19.4+8.8 ng/mL, p= 0.032). Binary logistic regression analysis showed that
      troponin I > 0.012 ng/ml is associated with increased phosphorus, increased
      calcium and decreased 25-OH vitamin D concentrations. A similar analysis using
      BNP >100 pg/mL failed to show signifcant associations with phosphorus, calcium
      and 25-OH vitamin D concentrations. CONCLUSIONS: In patients with stable coronary
      artery disease and preserved left ventricular function, those having cardiac
      troponin I > 0.012 ng/ml, but not those having BNP >100 pg/mL, had higher plasma
      phosphorus, higher plasma calcium and lower plasma 25-OH vitamin D concentrations
      than those having cardiac troponin I <= 0.012 ng/ml (or BNP <= 100 pg/mL).

PMID- 23552627
TI  - Analysis of alpha-klotho, fibroblast growth factor-, vitamin-D and calcium
      sensing receptor in 70 patients with secondary hyperparathyroidism.
AB  - BACKGROUND/AIMS: Secondary hyperparathyroidism (sHPT) is known as a very common
      complication in patients with chronic kidney disease, and G-protein-coupled
      calcium-sensing receptor (CaSR), Vitamin D receptor (VDR) and Fibroblast growth
      factor receptor (FGFR)/Klotho complexes seem to be involved in its development.
      METHODS: Hyperplastic parathyroid glands from 70 sHPT patients and normal
      parathyroid tissue from 7 patients were obtained during parathyroidectomy.
      Conventional morphological and immunohistochemical analysis of parathyroid glands
      was performed after dividing each slide in a 3x3 array. RESULTS: The presence of
      lipocytes in the normal parathyroid gland and tissue architecture (nodal in
      patients with sHPT) allows for discrimination between normal parathyroid glands
      and parathyroid glands of patients with sHPT. Protein expression of Klotho, FGFR,
      CaSR and VDR was higher in the normal parathyroid glands compared to the sHPT
      group (p<0.001, p=0.07, p =0.01 and p=0.001). The variability of each protein
      expression within each tissue slide was high. Therefore correlations between the
      different immunohistochemical variables were analyzed for each of the nine fields
      and than analyzed for all patients. Using this analysis, a highly significant
      positive correlation could be found between the expression of FGFR and VDR
      (p=0.0004). Interestingly, in terms of VDR we found a shift to a more mixed
      nuclear/cytoplasmic staining in the HPT group compared to normal parathyroid
      gland cells, which showed solitary nuclear staining for VDR (p>0.05).
      CONCLUSIONS: CaSR, VDR and an impaired Klotho-FGFR-axis seem to be the major
      players in the development of sHPT. Whether the detected correlation between FGFR
      and VDR and the shift to a more mixed nuclear/cytoplasmic staining of VDR will
      yield new insights into the pathogenesis of the disease has to be evaluated in
      further studies.

PMID- 23552629
TI  - Practice gaps. Underuse of dermoscopy in assessing Spitz nevi in children :
      comment on "Spitz nevi: beliefs, behaviors, and experiences of pediatric
      dermatologists".

PMID- 23552630
TI  - Influence of physician specialty on treatment recommendations in the
      multidisciplinary management of soft tissue sarcoma of the extremities.
AB  - IMPORTANCE: Although prospective randomized data are available to guide the
      multidisciplinary management of soft tissue sarcoma (STS) of the extremities,
      controversy exists regarding adjuvant chemotherapy and radiation therapy.
      OBJECTIVE: To determine if clinical specialty introduces bias in recommendations
      for multimodality treatment of STS. DESIGN: Electronic survey. SETTING: Database
      of active members of the American Society of Clinical Oncology, the Society of
      Surgical Oncology, and the Connective Tissue Oncology Society. PARTICIPANTS:
      Members of specialty oncology societies with an active interest in STS. EXPOSURE:
      Physician specialty. MAIN OUTCOMES AND MEASURES: Survey responses regarding the
      multidisciplinary management of STS were scored on a 5-point Likert scale and
      analyzed using analysis of variance. RESULTS: The questionnaire was completed by
      320 of 490 potential respondents (65%), including medical (18%), radiation (8%),
      orthopedic (22%), and surgical oncologists (45%). Respondents concurred on the
      use of radiation therapy for margins positive for tumor, for high-grade tumors,
      for improvement in local control, for tumors larger than 10 cm, and for tumors in
      close proximity to a neurovascular bundle. Respondents diverged on the use of
      radiation therapy for tumors 5 to 10 cm in size, for low-grade tumors, for
      radiation-associated STS, and for survival benefit. Only radiation oncologists
      felt that radiation therapy was underutilized as a treatment modality (mean [SEM]
      Likert scale score, 2.44 [0.12]; P < .001). There was agreement on the use of
      chemotherapy for synovial sarcoma, for high-grade tumors, for tumors larger than
      10 cm, for patients younger than 50 years of age, and for survival benefit.
      Medical oncologists were more likely to recommend chemotherapy for margins
      positive for tumor (mean [SEM] score, 3.12 [0.12]; P = .03) and for improvement
      in local control (mean [SEM] score, 2.91 [0.12] P = .08). Surgical oncologists
      placed the least emphasis on chemotherapy in the overall treatment plan (mean
      [SEM] score, 2.60 [0.07]; P = .001). CONCLUSIONS AND RELEVANCE: Specialty bias
      exists in adjuvant treatment recommendations for STS. This highlights the
      importance of multidisciplinary STS tumor boards and interdisciplinary care to
      facilitate consensus decision making for individual patients.

PMID- 23552631
TI  - Metastatic epidural bacterial abscess in a 4-year-old boy.

PMID- 23552632
TI  - Label-free in vivo imaging of human leukocytes using two-photon excited
      endogenous fluorescence.
AB  - We demonstrate that two-photon excited endogenous fluorescence enables label-free
      morphological and functional imaging of various human blood cells. Specifically,
      we achieved distinctive morphological contrast to visualize morphology of
      important leukocytes, such as polymorphonuclear structure of granulocyte and
      mononuclear feature of agranulocyte, through the employment of the reduced
      nicotinamide adenine dinucleotide (NADH) fluorescence signals. In addition, NADH
      fluorescence images clearly reveal the morphological transformation process of
      neutrophils during disease-causing bacterial infection. Our findings also show
      that time-resolved NADH fluorescence can be potentially used for functional
      imaging of the phagocytosis of pathogens by leukocytes (neutrophils) in vivo. In
      particular, we found that free-to-bound NADH ratios measured in infected
      neutrophils increased significantly, which is consistent with a previous study
      that the energy consumed in the phagocytosis of neutrophils is mainly generated
      through the glycolysis pathway that leads to the accumulation of free NADH.
      Future work will focus on further developing and applying label-free imaging
      technology to investigate leukocyte-related diseases and disorders.

PMID- 23552633
TI  - Ion-induced stacking of photosensitizer molecules can remarkably affect the
      luminescence detection of singlet oxygen in Candida albicans cells.
AB  - Singlet oxygen (1O2) is an important reactive intermediate in photodynamic
      reactions, particularly in antimicrobial PDT (aPDT). The detection of 1O2
      luminescence is frequently used to elucidate the role of 1O2 in various
      environments, particularly in microorganisms and human cells. When incubating the
      fungus, Candida albicans, with porphyrins XF73 (5,15-bis-[4-(3-Trimethylammonio
      propyloxy)-phenyl]-porphyrin) or TMPyP (5,10,15,20-Tetrakis(1-methyl-4-pyridinio)
      porphyrin tetra(p-toluenesulfonate)), the 1O2 luminescence signals were excellent
      for TMPyP. In case of XF73, the signals showed strange rise and decay times.
      Thus, 1O2 generation of XF73 was investigated and compared with TMPyP. Absorption
      spectroscopy of XF73 showed a change in absorption cross section when there was a
      change in the concentration from 1*10-6M to 1*10-3  M indicating an aggregation
      process. The addition of phosphate buffered saline (PBS) substantially changed
      1O2 luminescence in XF73 solution. Detailed experiments provided evidence that
      the PBS constituents NaCl and KCl caused the change of 1O2 luminescence. The
      results also indicate that Cl- ions may cause aggregation of XF73 molecules,
      which in turn enhances self-quenching of 1O2 via photosensitizer molecules. These
      results show that some ions, e.g., those present in cells in vitro or added by
      PBS, can considerably affect the detection and the interpretation of time
      resolved luminescence signals of 1O2, particularly in in vitro and in vivo. These
      effects should be considered for any other photosensitizer used in photodynamic
      processes.

PMID- 23552634
TI  - Two-dimensional and surface backscattering Mueller matrices of anisotropic sphere
      cylinder scattering media: a quantitative study of influence from fibrous
      scatterers.
AB  - We present both the two-dimensional backscattering point-illumination and surface
      illumination Mueller matrices for the anisotropic sphere-cylinder scattering
      media. The experimental results of the microsphere-silk sample show that the
      Mueller matrix elements of an anisotropic scattering medium are different from
      those of an isotropic medium. Moreover, both the experiments and Monte Carlo
      simulations show that the directions of the fibrous scatterers have prominent
      effects on the Mueller matrix elements. As the fibrous samples rotate, the
      surface-illumination Mueller matrix measurement results for the m12, m21, m13,
      m31, m22, m23, m32, and m33 elements represent periodical variations. Experiments
      on skeletal muscle and porcine liver tissue samples confirm that the periodical
      changes for the surface-illumination Mueller matrix elements are closely related
      to the well aligned fibrous scatterers. The m22, m23, m32, and m33 elements are
      powerful tools for quantitative characterization of anisotropic scattering media,
      including biological tissues.

PMID- 23552635
TI  - Rapid quantification of pixel-wise fiber orientation data in micrographs.
AB  - Defining fiber orientation at each pixel within a medical image has traditionally
      been computationally intensive and prone to systematic errors. A weighted
      orientation vector summation algorithm capable of detecting fiber orientation
      simultaneously at each pixel within an image is presented. As a result, pixel
      specific fiber orientation information with 2 deg to 3 deg accuracy can be
      determined within seconds, enabling the practical use of pixel-wise orientation
      data for characterizing structural anisotropy. This analysis technique has
      applicability and potential diagnostic utility for a variety of modalities,
      including second harmonic generation, scanning electron microscopy and
      immunohistochemical imaging is demonstrated.

PMID- 23552636
TI  - Elucidation of the mechanisms of optical clearing in collagen tissue with
      multiphoton imaging.
AB  - Optical clearing (OC) is a promising method to overcome limitations in biomedical
      depth-resolved optical studies. Mechanisms of OC in purified bovine Achilles
      tendon, chicken skin, and chicken tendon were studied using time-lapsed, three
      dimensional second harmonic generation (SHG) and two-photon fluorescence
      microscopic imaging. Quantified nonlinear optical measurements allowed temporal
      separation of two processes in collagen OC with glycerol. The first one is a fast
      process of tissue dehydration accompanied with collagen shrinkage and the second
      relatively slow process is glycerol penetration into the interfibrillar space of
      collagen alongside with CF swelling. The use of 50% glycerol induced less
      expressed OC via partial substitution of water molecules with glycerol molecules.
      We also found that phosphate-buffered saline- and glycerol-treatments were
      reversible, and fiber morphology and SHG signal intensity were recovered after
      the removal of immersion agents. It was shown that tissue OC was a dynamic
      process and elucidation of its physical mechanisms may help choose optimal
      diagnostic, treatment, and modification regimes for collagen-based as well as
      other types of biomaterials.

PMID- 23552637
TI  - Principal wavelengths in the formation of spectral images of natural scenes.
AB  - Considering the high degree of correlation in the visible spectrum, the principal
      wavelengths from spectral measurements of radiance recorded in spectral images
      were selected using a method based on principal components analysis (PCA). It
      seems to be that this is the first time that, instead of using spectra, data is
      taken directly from the "slices" of spectral images; the method has the advantage
      of preserving the structure of the original data in the reduced data set. A
      "true" dimensionality of five wavelengths resulted for all the analyzed images.
      The averages of the selected wavelengths for 10 spectral images produced good
      results for a human observer. These results were possible using only four
      wavelengths. Though PCA by itself is not able to include the impact of specific
      sensors on the selection of basis functions, results suggest that the variable
      selection method used in this work (which is not just PCA) yielded objective
      information of the structure of the physical stimuli (i.e., the spectral
      structures) that have been shaping the visual systems of animals and insects
      since many years ago.

PMID- 23552638
TI  - Detection of an unstable and/or a weak probe contact in a multichannel functional
      near-infrared spectroscopy measurement.
AB  - Multichannel functional near-infrared spectroscopy measurements involve the
      placement of many probes on a subject's head. A stable close contact between the
      probe and head surface is essential. We propose a way to detect two types of
      problematic probe contacts from the measurement data: an unstable contact whose
      light transmission easily fluctuates with body motion, and a weak contact whose
      light transmission is constantly small. An unstable contact causes large baseline
      fluctuation, whereas a weak contact causes large noise. Because absorbance
      changes caused by body motion and noise show different spectroscopic properties
      from the tissue hemoglobin absorption, they have a component orthogonal to the
      plane spanned by hemoglobin molar extinction coefficient vectors. We use this
      information to detect unstable and/or weak contacts. Probes are shared by
      different channels, and this sharing configuration is determined by the probe
      arrangement. Thus, the baseline fluctuation and noise of the channels are related
      to contact instability and weakness of the probe according to the probe
      arrangement. Unstable and/or weak probes are determined by solving an inverse
      problem of this relation. Problematic probes can be effectively determined using
      the proposed method.

PMID- 23552639
TI  - Constitutive activation of breast tumor kinase accelerates cell migration and
      tumor growth in vivo.
AB  - Breast tumor kinase (BRK) is a non-receptor tyrosine kinase overexpressed in most
      human breast tumors, including lymph node metastases, but undetected in normal
      mammary tissue or in fibroadenomas. The activity of BRK-like Src family tyrosine
      kinase, is regulated negatively by phosphorylation of C-terminal tyrosine 447.
      Although the kinase that regulates BRK activation has not been identified, we and
      others have previously shown that BRK-Y447F is a constitutively active variant.
      Because BRK-Y447F significantly enhances the catalytic activity of the enzyme, we
      investigated the role of the constitutively active BRK variant in tumor formation
      and metastasis. Using stable breast cancer cell MDA-MB-231 we observed
      significantly enhanced rates of cell proliferation, migration and tumor formation
      in BRK-Y447F stable cells compared with wild-type stable cell lines. Our results
      indicate full activation of BRK is an essential component in the tumorigenic role
      of BRK.

PMID- 23552640
TI  - CCR7-expressing B16 melanoma cells downregulate interferon-gamma-mediated
      inflammation and increase lymphangiogenesis in the tumor microenvironment.
AB  - The expression of the CC chemokine receptor-7 (CCR7) by cancers, including
      melanoma, augments lymph node (LN) metastasis, but little is known about its role
      in lymphangiogenesis and anti-tumor immunity. We injected control B16 murine
      melanoma cells (pLNCX2-B16) and CCR7-overexpressing B16 cells (CCR7-B16) in
      murine footpads and compared resulting tumors at the protein and mRNA level using
      immunostaining, Affymetrix gene microarray and quantitative reverse-transcriptase
      PCR. Although control and CCR7-B16 primary tumors were of similar size, LN
      metastasis was dramatically enhanced in CCR7-B16 tumors. Microarray analysis of
      leukocyte-depleted pLNCX2-B16 and CCR7-B16 tumor cell suspensions showed that
      three major groups of genes linked to interferon (IFN)-gamma signaling pathways
      (for example, STAT1, CXCR 9-11, CCL5 and CXCL10, major histocompatibility complex
      (MHC) I and MHC II) were downregulated in the CCR7-B16 tumor microenvironment,
      suggesting activation through CCR7 can downregulate pathways critical for host
      anti-tumor immunity. In addition, mRNA expression of the lymphatic marker
      podoplanin was upregulated in CCR7-B16 tumors by 3.35-fold versus control tumors.
      Anti-podoplanin monoclonal antibody staining revealed a three-fold increase in
      intratumoral CCL21-expressing lymphatic vessels, as well as a two-fold increase
      in the number of invading tumor cells per lymphatic vessel in CCR7-B16 versus
      control tumors. Enhanced anti-vascular endothelial growth factor C (VEGF-C)
      staining was present in CCR7-B16 versus control tumors, suggesting that VEGF-C
      may have a role in the CCR7-mediated lymphangiogenesis. In summary, CCR7-B16
      tumors show a striking decrease in IFN-gamma-mediated inflammatory gene
      expression in contrast to increased expression of VEGF-C, CCL21 and podoplanin by
      lymphatic vessels. Enhanced lymphangiogenesis may contribute to the dramatic
      increase in LN metastasis that is observed in the CCR7-expressing tumors.

PMID- 23552641
TI  - Trends in on-label and off-label modafinil use in a nationally representative
      sample.

PMID- 23552642
TI  - Improving the thermoelectric properties of half-Heusler TiNiSn through inclusion
      of a second full-Heusler phase: microwave preparation and spark plasma sintering
      of TiNi(1+x)Sn.
AB  - Half-Heusler thermoelectrics offer the possibility to choose from a variety of
      non-toxic and earth-abundant elements. TiNiSn is of particular interest and -
      with its relatively high electrical conductivity and Seebeck coefficient - allows
      for optimization of its thermoelectric figure of merit, reaching values of up to
      1 in heavily-doped and/or phase-segregated systems. In this contribution, we used
      an energy- and time-efficient process involving solid-state preparation in a
      commercial microwave oven and a fast consolidation technique, Spark Plasma
      Sintering, to prepare a series of Ni-rich TiNi1+xSn with small deviations from
      the half-Heusler composition. Spark Plasma Sintering plays an important role in
      the process by being a part of the synthesis of the material rather than solely a
      densification technique. Synchrotron powder X-ray diffraction and microprobe data
      confirm the presence of a secondary TiNi2Sn full-Heusler phase within the half
      Heusler matrix. We observe a clear correlation between the amount of full-Heusler
      phase and the lattice thermal conductivity of the samples, resulting in
      decreasing total thermal conductivity with increasing TiNi2Sn fraction. This
      trend shows that phonons are scattered effectively as a result of the
      microstructure of the materials with full-Heusler inclusions in the size range of
      microns to tens of microns. The best performing samples with around 5% of TiNi2Sn
      phase exhibit maximum figures of merit of almost 0.6 between 750 K and 800 K
      which is an increase of ca. 35% compared to the zT of the parent compound TiNiSn.

PMID- 23552643
TI  - Role of aromatic residues in amyloid fibril formation of human calcitonin by
      solid-state 13C NMR and molecular dynamics simulation.
AB  - Calcitonin (CT) is an amyloid fibril forming peptide. Since salmon calcitonin
      (sCT), having Leu residues (Leu12, Leu16 or Leu19) instead of Tyr12, Phe16 or
      Phe19 for human calcitonin (hCT), is known to form the fibrils much slower than
      hCT, hCTs mutated to Leu residues at the position of 16 (F16L-hCT), 19 (F19L
      hCT), and 12, 16 and 19 (TL-hCT) were examined to reveal the role of aromatic
      side-chains on amyloid fibrillation using solid-state (13)C NMR. The detailed
      kinetics were analyzed using a two-step reaction mechanism such as nucleation and
      fibril elongation with the rate constants of k1 and k2, respectively. The k2
      values of hCT mutants were significantly slower than that of hCT at a neutral pH,
      although they were almost the same at an acidic pH. The (13)C chemical shifts of
      the labeled sites showed that the conformations of monomeric hCT mutants take
      alpha-helices as viewed from the Gly10 moiety. The hCT mutants formed fibrils and
      during the fibril formation, the alpha-helix around Gly10-Phe22 changed to the
      beta-sheet, and the major structures around Ala26-Ala31 were random coil in the
      fibrils. Molecular dynamics simulation was performed for the beta-sheet system of
      hCT9-23 and its mutants F16L-hCT9-23, F19L-hCT9-23 and TL-hCT9-23. In one of the
      stable fibril structures, Phe16 of hCT interacts with Phe19 of the next strand
      alternatively. In the hCT mutants, lack of Phe16 and Phe19 interaction causes
      significant instability as compared with the hCT fibril, leading to the reduction
      of k2 values, as observed experimentally in the hCT mutants at a neutral pH.

PMID- 23552644
TI  - An energy policy that provides clean and green power.

PMID- 23552645
TI  - Science and politics of shale gas extraction.

PMID- 23552646
TI  - Public health and high volume hydraulic fracturing.
AB  - High-volume horizontal hydraulic fracturing (HVHF) in unconventional gas reserves
      has vastly increased the potential for domestic natural gas production. HVHF has
      been promoted as a way to decrease dependence on foreign energy sources, replace
      dirtier energy sources like coal, and generate economic development. At the same
      time, activities related to expanded HVHF pose potential risks including ground-
      and surface water contamination, climate change, air pollution, and effects on
      worker health. HVHF has been largely approached as an issue of energy economics
      and environmental regulation, but it also has significant implications for public
      health. We argue that public health provides an important perspective on
      policymaking in this arena. The American Public Health Association (APHA)
      recently adopted a policy position for involvement of public health professionals
      in this issue. Building on that foundation, this commentary lays out a set of
      five perspectives that guide how public health can contribute to this
      conversation.

PMID- 23552647
TI  - Using ethnography to monitor the community health implications of onshore
      unconventional oil and gas developments: examples from Pennsylvania's Marcellus
      Shale.
AB  - The ethnographer's toolbox has within it a variety of methods for describing and
      analyzing the everyday lives of human beings that can be useful to public health
      practitioners and policymakers. These methods can be employed to uncover
      information on some of the harder-to-monitor psychological, sociocultural, and
      environmental factors that may lead to chronic stress in individuals and
      communities. In addition, because most ethnographic research studies involve deep
      and long-term engagement with local communities, the information collected by
      ethnographic researchers can be useful in tracking long- and short-term changes
      in overall well-being and health. Set within an environmental justice framework,
      this article uses examples from ongoing ethnographic fieldwork in the Marcellus
      Shale gas fields of Pennsylvania to describe and justify using an ethnographic
      approach to monitor the psychological and sociocultural determinants of community
      health as they relate to unconventional oil and gas development projects in the
      United States.

PMID- 23552648
TI  - Investigating links between shale gas development and health impacts through a
      community survey project in Pennsylvania.
AB  - Across the United States, the race for new energy sources is picking up speed and
      reaching more places, with natural gas in the lead. While the toxic and polluting
      qualities of substances used and produced in shale gas development and the
      general health effects of exposure are well established, scientific evidence of
      causal links has been limited, creating an urgent need to understand health
      impacts. Self-reported survey research documenting the symptoms experienced by
      people living in proximity to gas facilities, coupled with environmental testing,
      can elucidate plausible links that warrant both response and further
      investigation. This method, recently applied to the gas development areas of
      Pennsylvania, indicates the need for a range of policy and research efforts to
      safeguard public health.

PMID- 23552649
TI  - The economic impact of shale gas development on state and local economies:
      benefits, costs, and uncertainties.
AB  - It is often assumed that natural gas exploration and development in the Marcellus
      Shale will bring great economic prosperity to state and local economies.
      Policymakers need accurate economic information on which to base decisions
      regarding permitting and regulation of shale gas extraction. This paper provides
      a summary review of research findings on the economic impacts of extractive
      industries, with an emphasis on peer-reviewed studies. The conclusions from the
      studies are varied and imply that further research, on a case-by-case basis, is
      necessary before definitive conclusions can be made regarding both short- and
      long-term implications for state and local economies.

PMID- 23552650
TI  - Historical analysis of oil and gas well plugging in New York: is the regulatory
      system working?
AB  - The aim of this work was to evaluate New York State's regulatory program for
      plugging inactive oil and gas wells. Analysis of reports from the Division of
      Mineral Resources, Department of Environmental Conservation, reveals that three
      fourths of the state's abandoned oil and gas wells were never plugged. Inadequate
      enforcement efforts have resulted in steady increases of unplugged oil and gas
      wells abandoned since 1992. Further, no program exists or is proposed to monitor
      abandoned wells which were plugged. These results strongly suggest that
      comprehensive reform and increased agency resources would be required to
      effectively regulate conventional oil and gas development in New York. Industrial
      expansion into shale oil and gas development should be postponed to avoid adding
      stress to an already compromised regulatory system.

PMID- 23552651
TI  - Analysis of reserve pit sludge from unconventional natural gas hydraulic
      fracturing and drilling operations for the presence of technologically enhanced
      naturally occurring radioactive material (TENORM).
AB  - Soil and water (sludge) obtained from reserve pits used in unconventional natural
      gas mining was analyzed for the presence of technologically enhanced naturally
      occurring radioactive material (TENORM). Samples were analyzed for total gamma,
      alpha, and beta radiation, and specific radionuclides: beryllium, potassium,
      scandium, cobalt, cesium, thallium, lead-210 and -214, bismuth-212 and -214,
      radium-226 and -228, thorium, uranium, and strontium-89 and -90. Laboratory
      analysis confirmed elevated beta readings recorded at 1329 +/- 311 pCi/g.
      Specific radionuclides present in an active reserve pit and the soil of a
      leveled, vacated reserve pit included 232Thorium decay series (228Ra, 228Th,
      208Tl), and 226Radium decay series (214Pb, 214Bi, 210Pb) radionuclides. The
      potential for impact of TENORM to the environment, occupational workers, and the
      general public is presented with potential health effects of individual
      radionuclides. Current oversight, exemption of TENORM in federal and state
      regulations, and complexity in reporting are discussed.

PMID- 23552652
TI  - Community-based risk assessment of water contamination from high-volume
      horizontal hydraulic fracturing.
AB  - The risk of contaminating surface and groundwater as a result of shale gas
      extraction using high-volume horizontal hydraulic fracturing (fracking) has not
      been assessed using conventional risk assessment methodologies. Baseline (pre
      fracking) data on relevant water quality indicators, needed for meaningful risk
      assessment, are largely lacking. To fill this gap, the nonprofit Community
      Science Institute (CSI) partners with community volunteers who perform regular
      sampling of more than 50 streams in the Marcellus and Utica Shale regions of
      upstate New York; samples are analyzed for parameters associated with HVHHF.
      Similar baseline data on regional groundwater comes from CSI's testing of private
      drinking water wells. Analytic results for groundwater (with permission) and
      surface water are made publicly available in an interactive, searchable database.
      Baseline concentrations of potential contaminants from shale gas operations are
      found to be low, suggesting that early community-based monitoring is an effective
      foundation for assessing later contamination due to fracking.

PMID- 23552653
TI  - Disclosure of hydraulic fracturing fluid chemical additives: analysis of
      regulations.
AB  - Hydraulic fracturing is used to extract natural gas from shale formations. The
      process involves injecting into the ground fracturing fluids that contain
      thousands of gallons of chemical additives. Companies are not mandated by federal
      regulations to disclose the identities or quantities of chemicals used during
      hydraulic fracturing operations on private or public lands. States have begun to
      regulate hydraulic fracturing fluids by mandating chemical disclosure. These laws
      have shortcomings including nondisclosure of proprietary or "trade secret"
      mixtures, insufficient penalties for reporting inaccurate or incomplete
      information, and timelines that allow for after-the-fact reporting. These
      limitations leave lawmakers, regulators, public safety officers, and the public
      uninformed and ill-prepared to anticipate and respond to possible environmental
      and human health hazards associated with hydraulic fracturing fluids. We explore
      hydraulic fracturing exemptions from federal regulations, as well as current and
      future efforts to mandate chemical disclosure at the federal and state level.

PMID- 23552654
TI  - Marcellus Shale Drilling's Impact on the Dairy Industry in Pennsylvania: A
      Descriptive Report.
AB  - Unconventional natural gas drilling in Pennsylvania has accelerated over the past
      five years, and is unlikely to abate soon. Dairy farming is a large component of
      Pennsylvania's agricultural economy. This study compares milk production, number
      of cows, and production per cow in counties with significant unconventional
      drilling activity to that in neighboring counties with less unconventional
      drilling activity, from 1996 through 2011. Milk production and milk cows
      decreased in most counties since 1996, with larger decreases occurring from 2007
      through 2011 (when unconventional drilling increased substantially) in five
      counties with the most wells drilled compared to six adjacent counties with fewer
      than 100 wells drilled. While this descriptive study cannot draw a causal
      association between well drilling and decline in cows or milk production, given
      the importance of Pennsylvania's dairy industry and the projected increase in
      unconventional natural gas drilling, further research to prevent unintended
      economic and public health consequences is imperative.

PMID- 23552655
TI  - Insights on unconventional natural gas development from shale: an interview with
      Anthony R. Ingraffea by Adam Law.
AB  - Adam Law, M.D., interviewed Anthony R. Ingraffea, Ph.D., P.E., as part of a
      series of interviews funded by the Heinz Endowment. Dr. Ingraffea is the Dwight
      C. Baum Professor of Engineering at Cornell University, and has taught structural
      mechanics, finite element methods, and fracture mechanics at Cornell for 33
      years. He discusses issues related to hydraulic fracturing, including inherent
      risks, spatial intensity, and the importance of a multi-disciplinary organization
      in establishing a chain of evidence.

PMID- 23552656
TI  - Navigating medical issues in shale territory.
AB  - The introduction of natural gas drilling with high-volume hydraulic fracturing to
      Pennsylvania and neighboring states since 2004 has been accompanied by numerous
      reports of varied symptoms and illnesses by those living near these operations.
      Pollutants with established toxic effects in humans may be introduced into the
      environment at various points during gas extraction and processing. Some
      community residents, as well as employees of the natural gas industry, believe
      that their health has deteriorated as a result of these operations and have
      sought medical care from local practitioners, who may have limited access to
      immediate toxicological consultations. This article reviews taking an
      environmental exposure history in the context of natural gas activities,
      underscoring the importance of thorough and guided history-taking in the
      discovery of environmental exposure clusters. It also highlights the critical
      need for funding, research, and peer-reviewed studies to help generate the body
      of evidence that is needed by practitioners.

PMID- 23552657
TI  - Computational dosimetry of induced electric fields during realistic movements in
      the vicinity of a 3 T MRI scanner.
AB  - Medical staff working near magnetic resonance imaging (MRI) scanners are exposed
      both to the static magnetic field itself and also to electric currents that are
      induced in the body when the body moves in the magnetic field. However, there are
      currently limited data available on the induced electric field for realistic
      movements. This study computationally investigates the movement induced electric
      fields for realistic movements in the magnetic field of a 3 T MRI scanner. The
      path of movement near the MRI scanner is based on magnetic field measurements
      using a coil sensor attached to a human volunteer. Utilizing realistic models for
      both the motion of the head and the magnetic field of the MRI scanner, the
      induced fields are computationally determined using the finite-element method for
      five high-resolution numerical anatomical models. The results show that the time
      derivative of the magnetic flux density (dB/dt) is approximately linearly
      proportional to the induced electric field in the head, independent of the
      position of the head with respect to the magnet. This supports the use of dB/dt
      measurements for occupational exposure assessment. For the path of movement
      considered herein, the spatial maximum of the induced electric field is close to
      the basic restriction for the peripheral nervous system and exceeds the basic
      restriction for the central nervous system in the international guidelines. The
      99th percentile electric field is a considerably less restrictive metric for the
      exposure than the spatial maximum electric field; the former is typically 60-70%
      lower than the latter. However, the 99th percentile electric field may exceed the
      basic restriction for dB/dt values that can be encountered during tasks commonly
      performed by MRI workers. It is also shown that the movement-induced eddy
      currents may reach magnitudes that could electrically stimulate the vestibular
      system, which could play a significant role in the generation of vertigo-like
      sensations reported by people moving in a strong static magnetic field.

PMID- 23552658
TI  - Cancer surgery among American Indians.
AB  - IMPORTANCE: American Indians (AIs) have the poorest cancer survival rates of any
      U.S. ethnic group. Late diagnosis, poor access to specialty care, and delays in
      therapy likely contribute to excess mortality. Surgery plays a central role in
      therapy for solid organ cancer. OBJECTIVE: To determine whether operative
      outcomes also contribute to poor long-term survival among AI patients with
      cancer. DESIGN: Population-based retrospective cohort study comparing patient-
      and hospital-level factors and short-term operative outcomes for AI and non
      Hispanic white patients. Survey-weighted multivariate analyses assessed the
      effect of AI ethnicity on hospital location, in-hospital mortality, and prolonged
      length of stay. SETTING: A 20% stratified sample of all US community hospitals.
      PATIENTS: Patients undergoing oncologic resection for 1 of 20 malignant neoplasms
      in the Nationwide Inpatient Sample from January 1, 1998, through December 31,
      2009. MAIN OUTCOME MEASURE: In-hospital mortality, length of stay, and hospital
      location (rural vs urban). RESULTS: Of 740,878 patients who met our inclusion
      criteria, 3048 were AIs. The AI patients were younger, more likely to undergo
      cancer surgery at rural hospitals, and more likely to be admitted for nonelective
      procedures and had more comorbidities than non-Hispanic white patients of similar
      ages (all, P < .05). The AI patients had comparable inpatient mortality and
      length of stay. CONCLUSIONS AND RELEVANCE This investigation is the largest study
      of surgical outcomes among AIs to date and the first to focus on cancer surgery.
      This relatively young cohort does not experience poor outcomes after oncologic
      resection. Future research should uncover other factors in the continuum of
      cancer care that may contribute to the poor long-term survival of AI patients
      with cancer, including delivery of perioperative therapies.

PMID- 23552659
TI  - Impact of a palliative care consult service.
AB  - Established hospital palliative care consult services (PCCS) have been associated
      with reduced costs and length of stay, decreased symptom burden, and increased
      satisfaction with care. Using a retrospective case-control design, we analyzed
      administrative data of patients seen by PCCS while hospitalized at the Rochester,
      Minnesota Mayo Clinic hospitals from 2003 to 2008. The PCCS patients were matched
      to 3:1. A total of 1477 patients seen by the PCCS were matched with 4431 patients
      not seen. Costs for patients seen and discharged alive were US $35,449 (95%
      confidence interval [CI] US $34,157-US $36,686) compared to US $37,447 (95% CI US
      $36,734-US $38,126), without PCCS consultation. Costs for PCCS patients that died
      during hospitalization were US $54,940 (95% CI US $51,483-US $58,576) and non
      PCCS patients were US $79,660 (95% CI US $76,614-US $83,398).

PMID- 23552660
TI  - Communication as an approach to resolve conflict about the implementation of
      palliative care.
AB  - The main aim of palliative care is to provide relief from pain and distressing
      symptoms and to offer psychological and spiritual support to enhance the quality
      of life. We present a case of an elderly Chinese patient with major depressive
      disorder who was a doctor himself, and through his experience of treating
      patients had become afraid about the complications of advanced disease. He wished
      to forego treatment, which was in conflict with those of his family. This report
      highlights the role of the palliative medical team in improving outcomes through
      enabling communication to occur between the family and the patient to achieve the
      best outcomes. This should lead to better training provision for the involved
      medical staff.

PMID- 23552661
TI  - Professional boundary issues in pediatric palliative care.
AB  - This article explores the hypothesis that when a child has a life-limiting
      illness, the interpersonal boundaries between the patient, the patient's parents,
      and the health care team members differ from traditional provider, patient, and
      parent boundaries because of the unique dynamics of palliative care in
      pediatrics. Providers from the Journey's Palliative Care Team at Albany Medical
      Center completed a brief survey about working in pediatric palliative care and
      what ethical challenges they have faced in trying to maintain professional
      boundaries as new palliative care providers. A retrospective review of survey
      responses and a review of relevant literature offer insight into the various
      concerns reported by the Journey's team. Conclusions about delivering
      comprehensive ethically sound palliative care services may serve as a pathway for
      future studies. 

PMID- 23552662
TI  - The effect of pediatric knowledge on hospice care costs.
AB  - The cost of hospice care is rising. Although providing care for children at end
      of life may be costly for hospices, it is unclear whether or not gaining
      pediatric knowledge and even establishing a pediatric program may be done cost
      effectively. The purpose of our study was to examine the effect of possessing
      pediatric knowledge (i.e., pediatric program, pediatric experience) on core
      hospice care costs. Using 2002 to 2008 California hospice data, the findings of
      the regression analysis suggest that having pediatric knowledge does not
      significantly increase nursing, physician, and medical social service costs.
      Having a pediatric program was related to increased counseling costs. Our
      findings shed important light on the minimal costs incurred when hospices decide
      to develop pediatric knowledge. 

PMID- 23552663
TI  - The determinants of patients in a palliative care unit being discharged home in
      Japan.
AB  - In Japan, regarding the place of end-of-life care, many people preferred the
      home. However, there is a discrepancy between patients' wishes and the actual
      circumstances. The primary aim of this study was to explore the factors that
      determine discharge home of patients in a palliative care unit. A total of 31
      patients met the criteria. The patients who could be discharged home (group 1; n
      = 23) were compared with the others (group 2; n = 8). Palliative prognostic index
      was significantly lower in group 1 than in group 2 (P = .032). Regarding routes
      of feeding, oral intake was significantly higher in group 1 than in group 2 (P =
      .043). That is to say, factors determining discharge home of patients may be
      influenced by the patient's prognosis and the necessity of a feeding device. 

PMID- 23552665
TI  - Slight undercorrection following total knee arthroplasty results in superior
      clinical outcomes in varus knees.
AB  - PURPOSE: Restoration of correct alignment is one of the main objectives of total
      knee arthroplasty (TKA). However, the influence of residual malalignment on
      clinical and functional outcomes is currently uncertain. This study was therefore
      undertaken to ascertain its influence in patients undergoing TKA for varus
      osteoarthritis of the knee. METHODS: A cohort of 132 consecutive patients (143
      knees) with pre-operative varus alignment was evaluated with a mean follow-up
      period of 7.2 years. Based upon the post-operative alignment, patients were
      stratified into three groups: neutral, mild varus, and severe varus. These groups
      were compared with respect to clinical and functional outcomes. RESULTS: All
      patients had post-operative improvements in Knee Society Score (KSS). Knees that
      were left in mild varus scored significantly better for the KSS and the Western
      Ontario and McMaster Universities Arthritis Index, compared with knees that were
      corrected to neutral and knees that were left in severe varus exceeding 6 degrees
      . No revisions occurred in any of the groups at midterm follow-up. CONCLUSION:
      The results of this study contradict the conventional assumption that correction
      to neutral mechanical alignment leads to the best outcome following TKA. Patients
      with pre-operative varus had better clinical and functional outcome scores if the
      alignment was left in mild varus, as compared with patients with an alignment
      correction to neutral. LEVEL OF EVIDENCE: Therapeutic study, Level III.

PMID- 23552666
TI  - Indications and limitations of osteochondral autologous transplantation in
      osteochondritis dissecans of the talus.
AB  - PURPOSE: Osteochondral autologous transplantation (OAT) from the ipsilateral
      femoral lateral condyle in osteochondritis dissecans (OD) of the talus has shown
      good clinical results in the past. To further define, indications and limitations
      of OAT various factors have been discussed which might influence the clinical
      outcome. METHODS: In this study, the clinical outcome of OAT of 32 patients (mean
      follow-up 29 months) was evaluated by means of the American Orthopaedic Foot and
      Ankle Society (AOFAS) Ankle-Hindfoot Scale, ankle pain on the visual analogue
      scale (VAS), and Hospital for Special Surgery (HSS) Patella score. We then
      analysed the statistical correlation between clinical outcome and various
      variables such as age, pre-existing osteoarthritis, or size of the lesion.
      RESULTS: Median AOFAS score was 86 (range 68-100), median ankle pain on VAS was
      2.0 (range 0-5.5), and median HSS Patella score was 95 (range 35-100). Advanced
      age (above 40 years of age) was associated with a significantly lower HSS Patella
      score (80 vs. 97.5, p = 0.035). None of the other variables (obesity, pre
      existing osteoarthritis, size of the lesion, necessity of malleolar osteotomy,
      localization of the lesion, and number of previous surgeries) influenced the
      clinical outcome adversely. CONCLUSIONS: Osteochondral autologous transplantation
      in OD of the talus is a safe procedure with good clinical results. As advanced
      age is associated with higher donor-site morbidity, indication for OAT in older
      patients should be carefully considered. As none of the other variables affected
      the clinical outcome of OAT adversely, there is no contraindication for OAT, for
      example, in osteochondral lesions requiring more than one osteochondral grafts,
      lateral lesions, patients with BMI >25, pre-existing osteoarthritis, or failed
      previous surgery. LEVEL OF EVIDENCE: IV.

PMID- 23552667
TI  - The attic of the femoral tunnel in anterior cruciate ligament reconstruction: a
      comparison of outcomes of two suspensory femoral fixation systems.
AB  - PURPOSE: This study aimed to find answers to the following questions: (1) Is it
      possible to determine and measure the space between the top of the graft and
      entrance of implant tunnel by magnetic resonance imaging (MRI)? (2) Is there any
      correlation between the hole above the graft in femoral tunnel and the femoral
      tunnel widening? (3) Does the tunnel widening affect clinical outcomes? (4) Are
      clinical and radiological outcomes of Toggle Loc with Zip Loop implant-loop
      design better than Endobutton CL? METHODS: The operative data of two surgeons
      were analysed. One surgeon used Endobutton CL femoral fixation (E-CL group, n =
      46); the other used Toggle Loc with Zip Loop femoral fixation (TL-ZL group, n =
      32). At the last follow-up, clinical evaluation was performed with International
      Knee Documentation Committee Subjective Knee Form (IKDC), Tegner activity scale,
      Lysholm score, active and passive ROM, Lachman and pivot shift tests, and KT-1000
      arthrometer. Radiological evaluation including measurement of tunnel widening on
      X-ray and MRI and the height of attic of femoral tunnel (space above the graft in
      femoral tunnel) on MRI was performed. RESULTS: No difference was found in patient
      demographics, concomitant meniscal surgery and clinical outcomes. The femoral
      tunnel widening was evaluated significantly low in TL-ZL group on the PA X-ray
      and MRI. No difference was observed in the tibial tunnel widening on X-ray and
      MRI. A correlation between the height of attic of femoral tunnel and the femoral
      tunnel widening was determined. Thus, the greater the height of attic of femoral
      tunnel, the greater the femoral tunnel widening. No correlation was established
      between the tunnel widening and IKDC and Lysholm scores. CONCLUSIONS: The results
      of this study demonstrate that a positive correlation exists between the height
      of the attic of the femoral tunnel and femoral tunnel widening. Therefore,
      increasing the height of the attic of the femoral tunnel may contribute to graft
      motion, which would then enhance femoral tunnel widening. LEVEL OF EVIDENCE: III.

PMID- 23552668
TI  - A multiscalar photoluminescence approach to discriminate among semiconducting
      historical zinc white pigments.
AB  - In order to fully characterize the zinc white artists' pigment (ZnO), much used
      since the mid-nineteenth century, three samples collected in the early 20th
      century were studied using a combination of synchrotron and macroscopic
      photoluminescence spectroscopy and imaging. An improved microscope setup based on
      synchrotron microspectroscopy and microimaging was used to study the powders
      dispersed onto indium foil. The synchrotron setup offered a diffraction-limited
      resolution of 153 nm. The PL spectra of individual grains were measured and the
      distribution of particles' emission spectra was mapped at the nanoscale. The
      results revealed that while the samples have apparent homogeneous
      photoluminescence behavior at the macroscale (bulk), their PL signatures are
      inhomogeneous below 20 MUm. At the nanoscale the three powder samples have quite
      different PL signatures. Different sources, perhaps even different batches, of
      zinc white might be readily differentiated using this method.

PMID- 23552670
TI  - Merkel cell polyomavirus and HPV-17 associated with cutaneous squamous cell
      carcinoma arising in a patient with melanoma treated with the BRAF inhibitor
      dabrafenib.
AB  - IMPORTANCE: Approximately 10% to 25% of patients treated with BRAF inhibitors
      develop cutaneous squamous cell carcinoma (SCC), but the mechanism responsible
      has not yet been determined. We report what we believe to be the first case in
      which Merkel cell polyomavirus (MCPyV) and human papillomavirus subtype 17 (HPV
      17) were associated with cutaneous SCC that developed during treatment with the
      BRAF inhibitor dabrafenib. OBSERVATIONS: A 62-year-old woman with V600E BRAF 
      mutant metastatic melanoma enrolled in a phase 1 trial of dabrafenib, a selective
      inhibitor of V600-mutant BRAF kinase. During the first 6 weeks of treatment, the
      patient developed multiple skin lesions, including a 6-mm crusted papule on the
      left eyebrow, which was resected and, on pathology examination, revealed SCC. The
      DNA extracted from paraffin-embedded tissue was amplified by polymerase chain
      reaction for detection of MCPyV and epidermodysplasia verruciformis HPV (EV-HPV)
      types. Analysis of the cloned and sequenced polymerase chain reaction products
      revealed the presence of MCPyV and HPV-17 DNA. Other EV-HPV subtypes were not
      detected. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report
      demonstrating the coexistence of MCPyV and HPV-17 in cutaneous SCC. Because both
      viruses have oncogenic potential, their role in the development of BRAF inhibitor
      related SCC merits further investigation.

PMID- 23552672
TI  - Powerful tests for association on quantitative trait loci incorporating
      imprinting effects.
AB  - Genomic imprinting is an important epigenetic factor in complex traits study, and
      there has recently been considerable interest in association study for
      quantitative traits by incorporating imprinting. However, these methods need the
      assumptions of Hardy-Weinberg equilibrium or only use information from families
      with one child. In this paper, by taking imprinting into account and making no
      assumption about the distribution of the quantitative traits, we propose two
      novel classes of Q-C-TDTI(c) and Q-C-MAX(c) family-based association tests for
      quantitative traits. The tests flexibly accommodate family data with missing
      parental genotype and with multiple siblings. Q-C-TDTI(c) is derived from a two
      stage analysis, where in the first stage Q-C-PAT(c) is applied to test for
      imprinting effects and in the second stage we select the most appropriate
      statistic among three transmission disequilibrium tests for association according
      to the finding from Q-C-PAT(c). Another proposed Q-C-MAX(c) approach takes the
      maximum of the three statistics. Compared with the existing alternative methods,
      the simulation results demonstrate that the two proposed tests are robust to
      population stratification and have better performance for testing association
      under various scenarios. Further, the powerful and versatile Q-C-TDTI(c) test is
      applied to analyze Framingham Heart Study data. 

PMID- 23552671
TI  - Five linkage regions each harbor multiple type 2 diabetes genes in the African
      American subset of the GENNID Study.
AB  - We previously localized type 2 diabetes (T2D)-susceptibility genes to five
      chromosomal regions through a genome-wide linkage scan of T2D and age of
      diagnosis (AOD) in the African American subset of the GENNID sample. To follow up
      these findings, we repeated the linkage and association analysis using genotypes
      on an additional 9203 fine-mapping single nucleotide polymorphisms (SNPs)
      selected to tag genes under the linkage peaks. In each of the five regions, we
      confirmed linkage and inferred the presence of >=2 susceptibility genes. The
      evidence of multiple susceptibility genes consisted of: (1) multiple linkage
      peaks in four of the five regions; and (2) association of T2D and AOD with SNPs
      within >=2 genes in every region. The associated genes included 3 previously
      reported to associate with T2D or related traits (GRB10, NEDD4L, LIPG) and 24
      novel candidate genes, including genes in lipid metabolism (ACOXL) and cell-cell
      and cell-matrix adhesion (MAGI2, CLDN4, CTNNA2).

PMID- 23552673
TI  - Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia.
AB  - Opsismodysplasia is an autosomal recessive skeletal disorder characterized by
      facial dysmorphism, micromelia, platyspondyly and retarded bone maturation.
      Recently, mutations in the gene encoding inositol polyphosphate phosphatase-like
      1 (INPPL1) are found in several families with opsismodysplasia by a homozygosity
      mapping, followed by whole genome sequencing. We performed an exome sequencing in
      two unrelated Japanese families with opsismodysplasia and identified a novel
      INPPL1 mutation, c.1960_1962delGAG, in one family. The mutation is predicted to
      result in an in-frame deletion (p.E654del) within the central catalytic 5
      phosphate domain. Our results further support that INPPL1 is the disease gene for
      opsismodysplasia and that opsismodysplasia has genetic heterogeneity. 

PMID- 23552675
TI  - Commentary: Mumps vaccines: do we need a new one?

PMID- 23552676
TI  - Bacterial respiratory pathogens in children with inherited immune and airway
      disorders: nasopharyngeal carriage and disease risk.
AB  - Children with primary immunodeficiencies, sickle cell disease and cystic fibrosis
      are at risk to develop invasive bacterial infections caused by respiratory tract
      pathogens, in particular Streptococcus pneumoniae, Haemophilus influenzae and
      Staphylococcus aureus. This review article evaluates the role of nasopharyngeal
      colonization by these pathogens in the high prevalence of respiratory and
      invasive infections in children with inherited disorders affecting the immune
      system or the respiratory tract. We conclude that respiratory and invasive
      diseases that occur in children with primary immunodeficiencies or sickle cell
      disease are probably a result of increased nasopharyngeal colonization rates
      compared with healthy children. However, when the inherited disorder is
      characterized by local airway abnormalities such as in cystic fibrosis, enhanced
      nasopharyngeal colonization does not seem to play a major role in invasive
      disease risk. As the evidence for the role of nasopharyngeal colonization in
      disease risk in these specific patient groups partly comes from experimental
      studies and animal models, longitudinal studies in children are needed. Detailed
      understanding of the effect of colonization on the development of respiratory and
      invasive infections in children with primary immunodeficiencies, sickle cell
      disease or cystic fibrosis provides a justification for the selective
      introduction of vaccination and prophylactic antibiotic treatment.
      Recommendations for the use of (preventive) therapeutic strategies in these
      patient groups taking into account disease-specific immunologic mechanisms
      underlying colonization and disease are described.

PMID- 23552677
TI  - Do we really need to worry about Listeria in newborn infants?

PMID- 23552678
TI  - Back mass in a 13-year-old boy.

PMID- 23552679
TI  - Cor pulmonale as a rare presentation of pulmonary tuberculosis in a child.

PMID- 23552680
TI  - Diagnosis and treatment of suspected Kawasaki disease before the fifth day of
      illness.

PMID- 23552681
TI  - Reply: To PMID 22565293.

PMID- 23552682
TI  - Detection limits in pneumococcal carriage.

PMID- 23552683
TI  - Shigella keratitis in an HIV-exposed infant.

PMID- 23552686
TI  - ACP Journal Club. Amoxicillin/clavulanate vs placebo: more exacerbation cures,
      fewer recurrences in mild-to-moderate COPD.

PMID- 23552689
TI  - Interpretation of experimental hydrogen-bond enthalpies and entropies from COSMO
      polarisation charge densities.
AB  - In this work, experimental hydrogen-bond (HB) enthalpies measured in previous
      works for a wide range of acceptor molecules in dilute mixtures of 4-fluorophenol
      in non-polar solvents are quantified from COSMO polarisation charge densities
      sigma of HB acceptors (HBA). As well as previously demonstrated for quantum
      chemically calculated HB enthalpies, a good correlation of the experimental data
      with the polarisation charge densities is observed, covering an extended range of
      HBA (O, N, S, pi systems and halogens) ranging from very weak to strong hydrogen
      bonds. Furthermore, for the first time, a quantitative analysis of experimental
      HB entropies is performed for such a chemical diversity of HBA. A good
      quantification of these entropies is achieved using the polarisation charge
      density sigma as a descriptor in combination with the logarithm of a directional
      partition function Omega(HB). This partition function covers the directional and
      multiplicity entropy of HBA and is based on the sigma-proportional HB enthalpy
      expression taken from COSMO-RS. As a result, the experimental HB enthalpies and
      free energies of the ~300 HB complexes are quantified with an accuracy of ~2 kJ
      mol(-1) based on COSMO polarisation charge densities.

PMID- 23552688
TI  - Neuropathologic basis of age-associated brain atrophy.
AB  - IMPORTANCE: While brain volume changes are used as surrogate markers for
      Alzheimer disease neuropathology in clinical studies, the extent to which these
      changes are due to pathologic features of Alzheimer disease in the aging brain is
      not well established. This study aims to clarify the neuropathologic correlates
      of longitudinal brain atrophy. OBJECTIVE: To examine the association between
      brain atrophy during life and neuropathology in an elderly population. DESIGN:
      Autopsy study of a cohort of elderly individuals. SETTING: Community-based
      population. PARTICIPANTS: Seventy-one healthy elderly individuals were selected
      from participants of the Oregon Brain Aging Study for having an autopsy, more
      than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging
      scan within 36 months of death. MAIN OUTCOMES AND MEASURES: The associations
      between brain volume trajectories (ventricular, total brain, and hippocampal) and
      time interaction terms for neurofibrillary tangles, neuritic plaques, gross
      infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE epsilon4 presence,
      and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or
      dementia as time-varying covariates) were examined in mixed-effects models,
      adjusting for duration of follow-up and age at death. RESULTS: Ventricular volume
      trajectory was significantly associated with age, presence of infarcts,
      neurofibrillary tangle and neuritic plaque scores, APOE epsilon4 allele presence,
      and dementia diagnosis. Total brain volume trajectory was significantly
      associated with age and mild cognitive impairment diagnosis. Hippocampal volume
      trajectory was significantly associated with amyloid angiopathy. CONCLUSIONS AND
      RELEVANCE: Ventricular volume trajectory is more sensitive than total brain and
      hippocampal volume trajectories as a marker of accruing Alzheimer disease and
      vascular pathology in elderly individuals. The association between brain volume
      trajectories and cognitive impairment (mild cognitive impairment and dementia)
      remained after controlling for the degree of neuropathology and other covariates.
      This suggests that there may be other factors not measured in this study that
      could be contributing to brain atrophy in those with cognitive impairment.

PMID- 23552690
TI  - RhoA is down-regulated at cell-cell contacts via p190RhoGAP-B in response to
      tensional homeostasis.
AB  - Breast epithelial cells cultured in three-dimensional (3D) collagen gels undergo
      ductal morphogenesis when the gel is compliant and they can achieve tensional
      homeostasis. We previously showed that this process requires down-regulation of
      Rho in compliant collagen gels, but the mechanism remains undefined. In this
      study, we find that p190RhoGAP-B, but not p190RhoGAP-A, mediates down-regulation
      of RhoA activity and ductal morphogenesis in T47D cells cultured in compliant 3D
      collagen gels. In addition, both RhoA and p190RhoGAP-B colocalize with p120
      catenin at sites of cell-cell contact. The association between p190RhoGAP-B and
      p120-catenin is regulated by matrix compliance such that it increases in
      compliant vs. rigid collagen gels. Furthermore, knockdown of p120-catenin
      disrupts ductal morphogenesis, disregulates RhoA activity, and results in loss of
      p190B at cell-cell contacts. Consistent with these findings, using a RhoA
      specific FRET biosensor (RhoA-FLARE.sc), we determined spatial RhoA activity to
      be significantly decreased at cell-cell contacts versus cell-ECM adhesions, and,
      of importance, spatial RhoA activity is regulated by p190B. This finding suggests
      that RhoA exists as an inactive pool at cell-cell contacts and is recruited to
      cell-ECM contacts within stiff matrices. Overall, these results demonstrate that
      RhoA is down-regulated at cell-cell contacts through p190RhoGAP-B, which is
      localized to cell-cell contacts by association with p120-catenin that is
      regulated by tensional homeostasis.

PMID- 23552691
TI  - Sumoylation of AMPKbeta2 subunit enhances AMP-activated protein kinase activity.
AB  - AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is
      a heterotrimer composed of a catalytic alpha and two regulatory subunits (beta
      and gamma). AMPK activity is regulated allosterically by AMP and by the
      phosphorylation of residue Thr-172 within the catalytic domain of the AMPKalpha
      subunit by upstream kinases. We present evidence that the AMPKbeta2 subunit may
      be posttranslationally modified by sumoylation. This process is carried out by
      the E3-small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated
      STAT PIASy, which modifies the AMPKbeta2 subunit by the attachment of SUMO2 but
      not SUMO1 moieties. Of interest, AMPKbeta1 is not a substrate for this
      modification. We also demonstrate that sumoylation of AMPKbeta2 enhances the
      activity of the trimeric alpha2beta2gamma1 AMPK complex. In addition, our results
      indicate that sumoylation is antagonist and competes with the ubiquitination of
      the AMPKbeta2 subunit. This adds a new layer of complexity to the regulation of
      the activity of the AMPK complex, since conditions that promote ubiquitination
      result in inactivation, whereas those that promote sumoylation result in the
      activation of the AMPK complex.

PMID- 23552692
TI  - Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding
      sequence through multiple miRNA-mRNA interactions.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs involved in posttranscriptional
      regulation of protein-coding genes in various biological processes. In our
      preliminary miRNA microarray analysis, miR-375 was identified as the most
      underexpressed in human oral tumor versus controls. The purpose of the present
      study is to examine the function of miR-375 as a candidate tumor suppressor miRNA
      in oral cancer. Cancerous inhibitor of PP2A (CIP2A), a guardian of oncoprotein
      MYC, is identified as a candidate miR-375 target based on bioinformatics.
      Luciferase assay accompanied by target sequence mutagenesis elucidates five
      functional miR-375-binding sites clustered in the CIP2A coding sequence close to
      the C-terminal domain. Overexpression of CIP2A is clearly demonstrated in oral
      cancers, and inverse correlation between miR-375 and CIP2A is observed in the
      tumors, as well as in NCI-60 cell lines, indicating the potential generalized
      involvement of the miR-375-CIP2A relationship in many other cancers. Transient
      transfection of miR-375 in oral cancer cells reduces the expression of CIP2A,
      resulting in decrease of MYC protein levels and leading to reduced proliferation,
      colony formation, migration, and invasion. Therefore this study shows that
      underexpression of tumor suppressor miR-375 could lead to uncontrolled CIP2A
      expression and extended stability of MYC, which contributes to promoting
      cancerous phenotypes.

PMID- 23552693
TI  - beta1 integrin regulates Arg to promote invadopodial maturation and matrix
      degradation.
AB  - beta1 integrin has been shown to promote metastasis in a number of tumor models,
      including breast, ovarian, pancreatic, and skin cancer; however, the mechanism by
      which it does so is poorly understood. Invasive membrane protrusions called
      invadopodia are believed to facilitate extracellular matrix degradation and
      intravasation during metastasis. Previous work showed that beta1 integrin
      localizes to invadopodia, but its role in regulating invadopodial function has
      not been well characterized. We find that beta1 integrin is required for the
      formation of mature, degradation-competent invadopodia in both two- and three
      dimensional matrices but is dispensable for invadopodium precursor formation in
      metastatic human breast cancer cells. beta1 integrin is activated during
      invadopodium precursor maturation, and forced beta1 integrin activation enhances
      the rate of invadopodial matrix proteolysis. Furthermore, beta1 integrin
      interacts with the tyrosine kinase Arg and stimulates Arg-dependent
      phosphorylation of cortactin on tyrosine 421. Silencing beta1 integrin with small
      interfering RNA completely abrogates Arg-dependent cortactin phosphorylation and
      cofilin-dependent barbed-end formation at invadopodia, leading to a significant
      decrease in the number and stability of mature invadopodia. These results
      describe a fundamental role for beta1 integrin in controlling actin
      polymerization-dependent invadopodial maturation and matrix degradation in
      metastatic tumor cells.

PMID- 23552694
TI  - The Drosophila F-box protein dSkp2 regulates cell proliferation by targeting
      Dacapo for degradation.
AB  - Cell cycle progression is controlled by a complex regulatory network consisting
      of interacting positive and negative factors. In humans, the positive regulator
      Skp2, an F-box protein, has been a subject of intense investigation in part
      because of its oncogenic activity. By contrast, the molecular and developmental
      functions of its Drosophila homologue, dSkp2, are poorly understood. Here we
      investigate the role of dSkp2 by focusing on its functional relationship with
      Dacapo (Dap), the Drosophila homologue of the cyclin-dependent kinase inhibitors
      p21(cip1)/p27(kip1)/p57(kip2). We show that dSkp2 interacts physically with Dap
      and has a role in targeting Dap for ubiquitination and proteasome-mediated
      degradation. We present evidence that dSkp2 regulates cell cycle progression by
      antagonizing Dap in vivo. dSkp2 knockdown reduces cell density in the wing by
      prolonging the cell doubling time. In addition, the wing phenotype caused by
      dSkp2 knockdown resembles that caused by dap overexpression and can be partially
      suppressed by reducing the gene dose of dap. Our study thus documents a conserved
      functional relationship between dSkp2 and Dap in their control of cell cycle
      progression, suggesting the possibility of using Drosophila as a model system to
      study Skp2-mediated tumorigenesis.

PMID- 23552696
TI  - Activation of the AKT/cyclin D1/Cdk4 survival signaling pathway in radioresistant
      cancer stem cells.
AB  - Radioresistance, which is a major cause of failure of radiotherapy (RT), is
      proposed as one of the intrinsic characteristics of cancer stem cells (CSCs)
      whose unique DNA damage response (DDR), efficient DNA repair and resistance to
      apoptosis are thought to confer the phenotype. We have isolated surviving CSCs by
      exposure to long-term fractionated radiation for 82 days from HepG2 and A172
      cells (82FR-31NR cells). 82FR-31NR cells exhibited CSC properties, such as high
      expression of CSC marker CD133 and the ABC transporters (MDR1 and BCRP1), and
      high tumorigenic potential after transplantation into nude mice. The advantage of
      our isolated CSCs is that they can proliferate in as the same growth medium as
      that of parental cells without loss of CSC properties. Therefore, we can analyze
      DDR of non-stem cells and CSCs without any influences caused by different culture
      conditions. 82FR-31NR cells showed efficient DNA repair of radiation-induced DNA
      damage and radioresistance with activation of the AKT/cyclin D1 survival
      signaling pathway. In contrast, DNA damage persisted for a long time after
      irradiation in parental cells compared with isolated CSCs. Persisted DNA damage
      induced apoptosis in parental cells without activation of the AKT/cyclin D1
      pathway. Therefore, inhibition of the AKT/cyclin D1 pathway by an AKT inhibitor,
      API-2, or cyclin D1 siRNA resulted in a loss of efficient DNA repair and
      radiosensitization of 82FR-31NR cells. Furthermore, knockdown of Cdk4 by its
      siRNA or a Cdk4 inhibitor was sufficient to suppress radioresistance of CSCs. In
      this study, we present a newly discovered DDR regarding the AKT/cyclin D1/Cdk4
      pathway in response to radiation in CSCs. Combination of fractionated RT and
      reagents targeting the AKT/cyclin D1/Cdk4 pathway to eradicate CSCs would be
      effective therapeutic modality.

PMID- 23552697
TI  - The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens
      junctions integrity.
AB  - Epithelial cell-cell contacts are mediated by E-cadherin interactions, which are
      regulated by the balanced local activity of Rho GTPases. Despite the known
      function of Rho at adherens junctions (AJs), little is known about the spatial
      control of Rho activity at these sites. Here we provide evidence that in breast
      epithelial cells the Deleted in Liver Cancer 3 (DLC3) protein localizes to AJs
      and is essential for E-cadherin function. DLC3 is a still poorly characterized
      RhoA-specific GTPase-activating protein that is frequently downregulated in
      various types of cancer. We demonstrate that DLC3 depletion leads to
      mislocalization of E-cadherin and catenins, which was associated with impaired
      cell aggregation and increased migration. This is explained by aberrant local Rho
      signaling because ROCK inhibition restored cell-cell contacts in DLC3 knockdown
      cells. We thus identify DLC3 as a novel negative regulator of junctional Rho and
      propose that DLC3 loss contributes to carcinogenesis by compromising epithelial
      integrity.

PMID- 23552698
TI  - Genomic copy number alterations in clear cell renal carcinoma: associations with
      case characteristics and mechanisms of VHL gene inactivation.
AB  - Array comparative genomic hybridization was used to identify copy number
      alterations in clear cell renal cell carcinoma (ccRCC) patient tumors to identify
      associations with patient/clinical characteristics. Of 763 ccRCC patients, 412
      (54%) provided frozen biopsies. Clones were analyzed for significant copy number
      differences, adjusting for multiple comparisons and covariates in multivariate
      analyses. Frequent alterations included losses on: 3p (92.2%), 14q (46.8%), 8p
      (38.1%), 4q (35.4%), 9p (32.3%), 9q (31.8%), 6q (30.8%), 3q (29.4%), 10q (25.7%),
      13q (24.5%), 1p (23.5%) and gains on 5q (60.2%), 7q (39.6%), 7p (30.6%), 5p
      (26.5%), 20q (25.5%), 12q (24.8%), 12p (22.8%). Stage and grade were associated
      with 1p, 9p, 9q, 13q and 14q loss and 12q gain. Males had more alterations
      compared with females, independent of stage and grade. Significant differences in
      the number/types of alterations were observed by family cancer history, age at
      diagnosis and smoking status. Von Hippel-Lindau (VHL) gene inactivation was
      associated with 3p loss (P<E-05), and these cases had fewer alterations than wild
      type cases. The fragile site flanking the FHIT locus (3p14.2) represented a
      unique breakpoint among VHL hypermethylated cases, compared with wild-type cases
      and those with sequence changes. This is the first study of its size to
      investigate copy number alterations among cases with extensive patient,
      clinical/risk factor information. Patients characterized by VHL wild-type gene
      status (vs sequence alterations) and male (vs female) cases had more copy number
      alterations regardless of diagnostic stage and grade, which could relate to poor
      prognosis.

PMID- 23552699
TI  - miR-200b restoration and DNA methyltransferase inhibitor block lung metastasis of
      mesenchymal-phenotype hepatocellular carcinoma.
AB  - Epithelial-to-mesenchymal transition (EMT) is associated with poor prognosis and
      metastasis in hepatocellular carcinoma. We have previously demonstrated an in
      vivo model of liver cancer in which mesenchymal cells post-EMT demonstrate a high
      rate of invasive growth and metastasis. Here, we investigate the role of microRNA
      200 (miR-200) family members and epigenetic modifications on the maintenance of
      mesenchymal/metastatic phenotype after EMT. Mesenchymal cells post-EMT
      demonstrates high levels of E-box repressors Zeb1 and Zeb2 and downregulation of
      four miR-200 family members (miR-200a, miR-200b, miR-200c and miR-429). In
      addition, DNA sequencing after bisulfite modification demonstrates that several
      CpG sites within the E-cadherin promoter are methylated in mesenchymal cells. In
      mesenchymal cells, forced expression of miR-200b results in a significant
      increase in E-cadherin and a reduction in cell migration/invasion. Despite these
      mesenchymal-to-epithelial transition (MET) changes in vitro, there is no
      significant change in metastatic potential after miR-200b upregulation in vivo.
      After the mesenchymal cells were treated with combination of DNA
      methyltransferase (DNMT) inhibitor and upregulation of miR-200b, invasive
      phenotype was significantly reduced and metastatic potential was eliminated.
      Direct targeting of E-cadherin with short hairpin RNA does not restore metastatic
      potential after DNMT inhibition and miR-200b re-expression. In addition,
      restoration of E-cadherin alone was unable to block metastatic potential in
      primary mesenchymal cells. In conclusion, targeting mesenchymal liver cancer
      cells with miR-200b and DNMT inhibitor reduces metastatic potential irrespective
      of E-cadherin expression. Thus, the broader differentiation and MET effects of
      DNMT inhibition and miR-200b must be considered in terms of rescuing metastatic
      potential.

PMID- 23552701
TI  - A comprehensive study on the cell chemistry of the sodium superoxide (NaO2)
      battery.
AB  - This work reports on the cell chemistry of a room temperature sodium-oxygen
      battery using an electrolyte of diethylene glycol dimethyl ether (diglyme) and
      sodium trifluoromethanesulfonate (NaSO3CF3, sodium triflate). Different from
      lithium-oxygen cells, where lithium peroxide is found as the discharge product,
      sodium superoxide (NaO2) is formed in the present cell, with overpotentials as
      low as 100 mV during charging. Several analytical methods are used to follow the
      cell reaction during discharge and charge. Changes in structure and morphology
      are studied by SEM and XRD. It is found that NaO2 grows as cubic particles with
      feed sizes in the range of 10-50 MUm; upon recharge the particles consecutively
      decompose. Pressure monitoring during galvanostatic cycling shows that the
      coulombic efficiency (e(-)/O2) for discharge and charge is approx. 1.0, the
      expected value for NaO2 formation. Also optical spectroscopy is identified as a
      convenient and useful tool to follow the discharge-charge process. The maximum
      discharge capacity is found to be limited by oxygen transport within the
      electrolyte soaked carbon fiber cathode and pore blocking near the oxygen
      interface is observed. Finally electrolyte decomposition and sodium dendrite
      growth are identified as possible reasons for the limited capacity retention of
      the cell. The occurrence of undesired side reactions is analyzed by DEMS
      measurements during cycling as well as by post mortem XPS investigations. 

PMID- 23552700
TI  - The tumor suppressor RASSF10 is upregulated upon contact inhibition and
      frequently epigenetically silenced in cancer.
AB  - The Ras association domain family (RASSF) comprises a group of tumor suppressors
      that are frequently epigenetically inactivated in various tumor entities and
      linked to apoptosis, cell cycle control and microtubule stability. In this work,
      we concentrated on the newly identified putative tumor suppressor RASSF10.
      Methylation analysis reveals RASSF10 promoter hypermethylation in lung cancer,
      head and neck (HN) cancer, sarcoma and pancreatic cancer. An increase in RASSF10
      methylation from normal tissues, primary tumors to cancer cell lines was
      observed. Methylation was reversed by 5-aza-2'-deoxycytidine treatment leading to
      reexpression of RASSF10. We further show that overexpression of RASSF10
      suppresses colony formation in cancer cell lines. In addition, RASSF10 is
      upregulated by cell-cell contact and regulated on promoter level as well as
      endogenously by forskolin, protein kinase A (PKA) and activator Protein 1 (AP-1),
      linking RASSF10 to the cAMP signaling pathway. Knockdown of the AP-1 member JunD
      interfered with contact inhibition induced RASSF10 expression. In summary, we
      found RASSF10 to be epigenetically inactivated by hypermethylation of its CpG
      island promoter in lung, HN, sarcoma and pancreatic cancer. Furthermore, our
      novel findings suggest that tumor suppressor RASSF10 is upregulated by PKA and
      JunD signaling upon contact inhibition and that RASSF10 suppresses growth of
      cancer cells.

PMID- 23552702
TI  - New drug update: 2012.
AB  - Five new drugs that are used for medical problems often experienced by the
      elderly have been selected for consideration in this review. The uses and most
      important properties of these agents are considered, and a rating for each new
      drug is determined. The rating is based on a comparison of the new drug with
      related drugs already marketed. Advantages, disadvantages, and other important
      information regarding the new drug are identified and used as the basis for
      determining the rating.

PMID- 23552703
TI  - Preventing pneumococcal disease: intergenerational issues.
AB  - In the United States, approximately four million people contract pneumococcal
      infections each year, and elders and children are at an increased risk of
      contracting these infections. Since the late 1800s, researchers have searched for
      a vaccine that covers the many serotypes of Streptococcus pneumoniae. Today,
      three vaccines are available, and each possesses subtle differences.
      Notwithstanding the positive impact from each vaccine type, the incidence of
      diseases caused by serotypes that are not included in specific vaccines tends to
      increase in children and certain adult populations with underlying illnesses.
      While these increases are usually small compared with the overall reduction in
      disease, some clinicians and patients question the effectiveness of vaccinations.
      Pharmacists need to promote pneumococcal vaccination and emphasize the need to
      also receive annual influenza vaccine.

PMID- 23552704
TI  - Development and evaluation of a student-led Medicare Part D Planning Clinic.
AB  - OBJECTIVE: To describe the creation of a student-led Medicare Part D Planning
      Clinic and to present satisfaction survey data evaluating the clinic. DESIGN:
      Prospective pre- and post-assessment satisfaction surveys. SETTING: University of
      Arkansas for Medical Sciences Institute on Aging. PATIENTS, PARTICIPANTS:
      Medicare beneficiaries in 2011 in Arkansas. INTERVENTIONS: The Medicare Part D
      Planning Clinic aids seniors in making a well-informed decision on which Medicare
      Part D plan is best for them. Pharmacy students learn about Medicare Part D
      choices and interact with older adults assisting them in identifying the best
      plan. MAIN OUTCOME MEASURE(S): Potential mean and overall savings and
      satisfaction ratings. RESULTS: Forty-eight patients were seen at the clinic in
      2011, and 25 of those patients were shown to have potential savings if they
      switched plans with an average potential annual savings of $1,157 per patient and
      a total potential annual savings of $28,929. Among both new and current Part D
      beneficiaries, 100% indicated they were very satisfied with the service, and
      among current Part D beneficiaries who completed the surveys, the percent that
      believed they would have to delay or not fill a prescription because of cost was
      18.8% on the pre-assessment survey and 9.1% on the post-assessment survey.
      CONCLUSION: Offering these services is an effective way to potentially save out
      of-pocket expenses among seniors, and seniors find this service satisfying and
      helpful.

PMID- 23552705
TI  - Galantamine-associated nightmares and anxiety.
AB  - BACKGROUND: This case report describes recurrent nightmares and anxiety possibly
      caused by the administration and rapid dose titration of galantamine. CASE
      SUMMARY: A 90-year-old male with Alzheimer's disease was initiated on galantamine
      4 mg twice daily for 10 days, followed by 8 mg twice daily thereafter. On
      followup to the geriatric clinic, the patient reported complaints of nightmares
      and associated anxiety. The occurrences of nightmares developed after initiating
      galantamine and temporally increased with galantamine titration. After
      discontinuation of galantamine, the patient reported no further occurrences of
      nightmares or anxiety and memory function remained stable. CONCLUSION:
      Galantamine-associated nightmares are an uncommon adverse event and may have been
      exacerbated by rapid titration. Although such adverse events are unlikely to
      cause harm in the patient, such sleep abnormalities have the potential to
      decrease a patient's quality of life and may require the need for alternative
      therapy.

PMID- 23552706
TI  - Antacid-induced acute pancreatitis.
AB  - OBJECTIVE: To report a case of acute pancreatitis associated with the
      administration of high doses of over-the-counter (OTC) antacids containing
      calcium carbonate. SETTING: An acute care 276-bed community hospital. CASE
      SUMMARY: In this case report, a 68-year-old male was admitted to the hospital for
      nausea, vomiting, and stomach pain. Patient reported taking 15-20 OTC calcium
      carbonate (4.5-6.0 g elemental calcium) tablets for four to five days prior to
      admission. Patient's calcium level upon admission was 18.5 mg/dL. Laboratory
      values of amylase and lipase peaked at 2,768 U/L and 7,091 U/L, respectively. An
      abdominal computed tomography confirmed acute pancreatitis. For a period of 45
      days, treatment in the intensive care unit for acute pancreatitis and latter for
      necrotizing pancreatitis was conducted. CONCLUSION: This case study supports an
      association between hypercalcemia and pancreatitis in patients who take greater
      than recommended dosages of calcium-containing antacids. OTC antacids are
      popular, but can cause serious adverse events when not used as directed.

PMID- 23552709
TI  - Impact of minimally invasive surgery on medical spending and employee
      absenteeism.
AB  - IMPORTANCE: As many surgical procedures have undergone a transition from a
      standard, open surgical approach to a minimally invasive one in the past 2
      decades, the diffusion of minimally invasive surgery may have had sizeable but
      overlooked effects on medical expenditures and worker productivity. OBJECTIVE: To
      examine the impact of standard vs minimally invasive surgery on health plan
      spending and workplace absenteeism for 6 types of surgery. DESIGN: Cross
      sectional regression analysis. SETTING: National health insurance claims data and
      matched workplace absenteeism data from January 1, 2000, to December 31, 2009.
      PARTICIPANTS: A convenience sample of adults with employer-sponsored health
      insurance who underwent either standard or minimally invasive surgery for
      coronary revascularization, uterine fibroid resection, prostatectomy, peripheral
      revascularization, carotid revascularization, or aortic aneurysm repair. MAIN
      OUTCOMES AND MEASURE: Health plan spending and workplace absenteeism from 14 days
      before through 352 days after the index surgery. RESULTS: There were 321,956
      patients who underwent surgery; 23,814 were employees with workplace absenteeism
      data. After multivariable adjustment, mean health plan spending was lower for
      minimally invasive surgery for coronary revascularization (-$30,850; 95% CI, 
      $31,629 to -$30,091), uterine fibroid resection (-$1509; 95% CI, -$1754 to 
      $1280), and peripheral revascularization (-$12,031; 95% CI, -$15,552 to -$8717)
      and higher for prostatectomy ($1350; 95% CI, $611 to $2212) and carotid
      revascularization ($4900; 95% CI, $1772 to $8370). Undergoing minimally invasive
      surgery was associated with missing significantly fewer days of work for coronary
      revascularization (mean difference, -37.7 days; 95% CI, -41.1 to -34.3), uterine
      fibroid resection (mean difference, -11.7 days; 95% CI, -14.0 to -9.4),
      prostatectomy (mean difference, -9.0 days; 95% CI, -14.2 to -3.7), and peripheral
      revascularization (mean difference, -16.6 days; 95% CI, -28.0 to -5.2).
      CONCLUSIONS AND RELEVANCE: For 3 of 6 types of surgery studied, minimally
      invasive procedures were associated with significantly lower health plan spending
      than standard surgery. For 4 types of surgery, minimally invasive procedures were
      consistently associated with significantly fewer days of absence from work.

PMID- 23552714
TI  - Laparoscopic vs. open incisional hernia repair: a randomized clinical trial.
AB  - IMPORTANCE: Incisional hernia is the most frequent surgical complication after
      laparotomy. Up to 30% of all patients undergoing laparotomy develop an incisional
      hernia. OBJECTIVE: To compare laparoscopic vs open ventral incisional hernia
      repair with regard to postoperative pain and nausea, operative results,
      perioperative and postoperative complications, hospital admission, and recurrence
      rate. DESIGN: Multicenter randomized controlled trial between May 1999 and
      December 2006 with a mean follow-up period of 35 months. SETTING: All patients
      were operated on in a clinical setting at 1 of the 2 participating university
      medical centers or at the other 8 teaching hospitals. PARTICIPANTS: Two hundred
      six patients from 10 hospitals were randomized equally to laparoscopic or open
      mesh repair. Patients with an incisional hernia larger than 3 cm and smaller than
      15 cm, either primary or recurrent, were included. Patients were excluded if they
      had an open abdomen treatment in their medical histories. INTERVENTION:
      Laparoscopic or open ventral incisional hernia repair. MAIN OUTCOME MEASURES: The
      primary outcome of the trial was postoperative pain. Secondary outcomes were use
      of analgesics, perioperative and postoperative complications, operative time,
      postoperative nausea, length of hospital stay, recurrence, morbidity, and
      mortality. RESULTS: Median blood loss during the operation was significantly less
      (10 mL vs 50 mL; P = .05) as well as the number of patients receiving a wound
      drain (3% vs. 45%; P < .001) in the laparoscopic group. Operative time for the
      laparoscopic group was longer (100 minutes vs. 76 minutes; P = .001).
      Perioperative complications were significantly higher after laparoscopy (9% vs.
      2%). Visual analog scale scores for pain and nausea, completed before surgery and
      3 days and 1 and 4 weeks postoperatively, showed no significant differences
      between the 2 groups. At a mean follow-up period of 35 months, a recurrence rate
      of 14% was reported in the open group and 18%, in the laparoscopic group (P =
      .30). The size of the defect was found to be an independent predictor for
      recurrence (P < .001). CONCLUSIONS AND RELEVANCE: During the operation, there was
      less blood loss and less need for a wound drain in the laparoscopic group.
      However, operative time was longer during laparoscopy. Perioperative
      complications were significantly higher in the laparoscopic group. Visual analog
      scores for pain and nausea did not differ between groups. The incidence of a
      recurrence was similar in both groups. The size of the defect was found to be an
      independent factor for recurrence of an incisional hernia.

PMID- 23552716
TI  - Hair-shaft abnormality in a 7-year-old girl. Trichorrhexis nodosa dueto
      biotinidase deficiency.

PMID- 23552717
TI  - Cramer-Rao lower bound optimization of an EM-CCD-based scintillation gamma
      camera.
AB  - Scintillation gamma cameras based on low-noise electron multiplication (EM-)CCDs
      can reach high spatial resolutions. For further improvement of these gamma
      cameras, more insight is needed into how various parameters that characterize
      these devices influence their performance. Here, we use the Cramer-Rao lower
      bound (CRLB) to investigate the sensitivity of the energy and spatial resolution
      of an EM-CCD-based gamma camera to several parameters. The gamma camera setup
      consists of a 3 mm thick CsI(Tl) scintillator optically coupled by a fiber optic
      plate to the E2V CCD97 EM-CCD. For this setup, the position and energy of
      incoming gamma photons are determined with a maximum-likelihood detection
      algorithm. To serve as the basis for the CRLB calculations, accurate models for
      the depth-dependent scintillation light distribution are derived and combined
      with a previously validated statistical response model for the EM-CCD. The
      sensitivity of the lower bounds for energy and spatial resolution to the EM gain
      and the depth-of-interaction (DOI) are calculated and compared to experimentally
      obtained values. Furthermore, calculations of the influence of the number of
      detected optical photons and noise sources in the image area on the energy and
      spatial resolution are presented. Trends predicted by CRLB calculations agree
      with experiments, although experimental values for spatial and energy resolution
      are typically a factor of 1.5 above the calculated lower bounds. Calculations and
      experiments both show that an intermediate EM gain setting results in the best
      possible spatial or energy resolution and that the spatial resolution of the
      gamma camera degrades rapidly as a function of the DOI. Furthermore, calculations
      suggest that a large improvement in gamma camera performance is achieved by an
      increase in the number of detected photons or a reduction of noise in the image
      area. A large noise reduction, as is possible with a new generation of EM-CCD
      electronics, may improve the energy and spatial resolution by a factor of 1.5.

PMID- 23552719
TI  - ACP Journal Club. Review: lower rather than higher tidal volume benefits
      ventilated patients without ARDS.

PMID- 23552720
TI  - Permanent and temporary epiphysiodesis: an experimental study in a rabbit model.
AB  - OBJECTIVE: The aim of this study was to compare the Phemister technique
      (permanent epiphysiodesis) with temporary epiphysiodesis with stapling and
      evaluate the degree of epiphyseal plate activity following staple removal using
      radiographic, scintigraphic and histopathologic methods and to investigate
      whether bone scintigraphy could provide clues on expected physis activity.
      METHODS: This study included 24 New Zealand rabbits divided into three groups of
      8. Group 1 underwent Phemister's epiphysiodesis; Group 2, epiphysiodesis with
      stapling; and Group 3, epiphysiodesis stapling group with staples removed in the
      3rd week. Radiological and scintigraphic data were recorded in the 3rd and 6th
      weeks. All animals were sacrificed for histopathological evaluation at the 6th
      week. Limb length was calculated using radiological assessment and their growth
      plate activation recorded from scintigraphic region of interest (ROI) assessment
      in the 3rd and 6th weeks. Histopathological findings of the growth plate were
      measured using qualitative and quantitative methods. All data were compared to
      the non-operated right side. RESULTS: Group 1 had effective scintigraphic,
      radiologic and histopathological findings than the other groups (p<0.05). In
      Group 3, growth plate activation was detected to be higher than the regular
      physis activity (p<0.05). CONCLUSION: Preoperative and postoperative scintigraphy
      combined with radiological assessment can provide an idea on the reversibility of
      growth plate activation.

PMID- 23552721
TI  - Using social networking to understand social networks: analysis of a mobile phone
      closed user group used by a Ghanaian health team.
AB  - BACKGROUND: The network structure of an organization influences how well or
      poorly an organization communicates and manages its resources. In the Millennium
      Villages Project site in Bonsaaso, Ghana, a mobile phone closed user group has
      been introduced for use by the Bonsaaso Millennium Villages Project Health Team
      and other key individuals. No assessment on the benefits or barriers of the use
      of the closed user group had been carried out. OBJECTIVE: The purpose of this
      research was to make the case for the use of social network analysis methods to
      be applied in health systems research--specifically related to mobile health.
      METHODS: This study used mobile phone voice records of, conducted interviews
      with, and reviewed call journals kept by a mobile phone closed user group
      consisting of the Bonsaaso Millennium Villages Project Health Team. Social
      network analysis methodology complemented by a qualitative component was used.
      Monthly voice data of the closed user group from Airtel Bharti Ghana were
      analyzed using UCINET and visual depictions of the network were created using
      NetDraw. Interviews and call journals kept by informants were analyzed using
      NVivo. RESULTS: The methodology was successful in helping identify effective
      organizational structure. Members of the Health Management Team were the more
      central players in the network, rather than the Community Health Nurses (who
      might have been expected to be central). CONCLUSIONS: Social network analysis
      methodology can be used to determine the most productive structure for an
      organization or team, identify gaps in communication, identify key actors with
      greatest influence, and more. In conclusion, this methodology can be a useful
      analytical tool, especially in the context of mobile health, health services, and
      operational and managerial research.

PMID- 23552722
TI  - Preclinical studies in the mdx mouse model of duchenne muscular dystrophy with
      the histone deacetylase inhibitor givinostat.
AB  - Previous work has established the existence of dystrophin-nitric oxide (NO)
      signaling to histone deacetylases (HDACs) that is deregulated in dystrophic
      muscles. As such, pharmacological interventions that target HDACs (that is, HDAC
      inhibitors) are of potential therapeutic interest for the treatment of muscular
      dystrophies. In this study, we explored the effectiveness of long-term treatment
      with different doses of the HDAC inhibitor givinostat in mdx mice--the mouse
      model of Duchenne muscular dystrophy (DMD). This study identified an efficacy for
      recovering functional and histological parameters within a window between 5 and
      10 mg/kg/d of givinostat, with evident reduction of the beneficial effects with 1
      mg/kg/d dosage. The long-term (3.5 months) exposure of 1.5-month-old mdx mice to
      optimal concentrations of givinostat promoted the formation of muscles with
      increased cross-sectional area and reduced fibrotic scars and fatty infiltration,
      leading to an overall improvement of endurance performance in treadmill tests and
      increased membrane stability. Interestingly, a reduced inflammatory infiltrate
      was observed in muscles of mdx mice exposed to 5 and 10 mg/kg/d of givinostat. A
      parallel pharmacokinetic/pharmacodynamic analysis confirmed the relationship
      between the effective doses of givinostat and the drug distribution in muscles
      and blood of treated mice. These findings provide the preclinical basis for an
      immediate translation of givinostat into clinical studies with DMD patients.

PMID- 23552723
TI  - Macrophage migration inhibitory factor (MIF) and thyroid hormone alterations in
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine known
      to be released from lymphocytes, macrophages and endothelial cells and also in
      animal models shown to be inducible with glucocorticoids (GC). In contrast,
      thyroxine seems to antagonize MIF activity. To investigate whether MIF is
      increased in active antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV) and possible correlations with GC dosing and thyroid hormone
      levels, 27 consecutive patients with active AAV were studied and followed
      prospectively. Disease activity was assessed using Birmingham Vasculitis Activity
      Score 2003 (BVAS) at baseline and at follow-up at 3 and 6 months, along with MIF,
      thyroid hormones free triiodothyronine (fT3) and free thyroxine (fT4), C-reactive
      protein (CRP) and creatinine. MIF was elevated significantly at baseline compared
      with follow-up at 3 and 6 months (8,618 pg/mL versus 5,696 and 6,212
      respectively; P < 0.002) but did not correlate to CRP, GC dose, creatinine or
      organ involvement. fT3 was depressed significantly at baseline compared with
      follow-up (1.99 pg/mL versus 2.31 and 2.67 respectively; P = 0.01) and correlated
      inversely to the BVAS score at baseline. We found a significant correlation
      between the MIF/fT4 ratio at baseline versus MIF/fT4 ratio at 6 months (rho =
      0.52, P < 0.005) and a trend between the baseline MIF/fT3 ratio versus MIF/fT3
      ratio at 6 months (rho = 0.39, P = 0.05). These results suggest a possible role
      for MIF and thyroid status in AAV. Further studies could reveal whether the
      association between AAV and thyroid hormone levels in the context of elevated MIF
      may present a link as well as a target of treatment.

PMID- 23552724
TI  - MFG-E8 and HMGB1 are involved in the mechanism underlying alcohol-induced
      impairment of macrophage efferocytosis.
AB  - Efferocytosis is a unique phagocytic process for macrophages to remove apoptotic
      cells in inflammatory loci. This event is maintained by milk fat globule-EGF
      factor 8 (MFG-E8), but attenuated by high mobility group box 1 (HMGB1). Alcohol
      abuse causes injury and inflammation in multiple tissues. It alters
      efferocytosis, but precise molecular mechanisms for this effect remain largely
      unknown. Here, we showed that acute exposure of macrophages to alcohol (25
      mmol/L) inhibited MFG-E8 gene expression and impaired efferocytosis. The effect
      was mimicked by hydrogen peroxide. Moreover, N-acetylcysteine (NAC), a potent
      antioxidant, blocked acute alcohol effect on inhibition of macrophage MFG-E8 gene
      expression and efferocytosis. In addition, recombinant MFG-E8 rescued the
      activity of alcohol-treated macrophages in efferocytosis. Together, the data
      suggest that acute alcohol exposure impairs macrophage efferocytosis via
      inhibition of MFG-E8 gene expression through a reactive oxygen species dependent
      mechanism. Alcohol has been found to suppress or exacerbate immune cell
      activities depending on the length of alcohol exposure. Thus, we further examined
      the role of chronic alcohol exposure on macrophage efferocytosis. Interestingly,
      treatment of macrophages with alcohol for seven days in vitro enhanced MFG-E8
      gene expression and efferocytosis. However, chronic feeding of mice with alcohol
      caused increase in HMGB1 levels in serum. Furthermore, HMGB1 diminished
      efferocytosis by macrophages that were treated chronically with alcohol,
      suggesting that HMGB1 might attenuate the direct effect of chronic alcohol on
      macrophage efferocytosis in vivo. Therefore, we speculated that the balance
      between MFG-E8 and HMGB1 levels determines pathophysiological effects of chronic
      alcohol exposure on macrophage efferocytosis in vivo.

PMID- 23552725
TI  - Potential of the trifunctional bispecific antibody surek depends on dendritic
      cells: rationale for a new approach of tumor immunotherapy.
AB  - Trifunctional bispecific antibodies (trAbs) used in tumor immunotherapy have the
      unique ability to recruit T cells toward antigens on the tumor cell surface and,
      moreover, to activate accessory cells through their immunoglobulin Fc region
      interacting with activating Fcgamma receptors. This scenario gives rise to
      additional costimulatory signals required for T cell-mediated tumor cell
      destruction and induction of an immunologic memory. Here we show in an in vitro
      system that most effective trAb-dependent T-cell activation and tumor cell
      elimination are achieved in the presence of dendritic cells (DCs). On the basis
      of these findings, we devise a novel approach of cancer immunotherapy that
      combines the specific advantages of trAbs with those of DC-based vaccination.
      Simultaneous delivery of trAbs and in vitro differentiated DCs resulted in a
      markedly improved tumor rejection in a murine melanoma model compared with
      monotherapy.

PMID- 23552727
TI  - Impact of short and long-range effects on the magnetic interactions in neutral
      organic radical-based materials.
AB  - The mutual influence of electronic structure and environment of the constituent
      units of neutral organic radical-based materials (radical dimers) is analysed by
      means of wave function calculations (Difference Dedicated Configuration
      Interaction, DDCI). Focus is put on the magnetic property modulations of two
      classes of neutral organic materials by inspecting both short- and long-range
      effects. The exchange coupling constant J for the high-temperature phase of the
      1,3,5-trithia-2,4,6-triazapentalenyl (TTTA) material is calculated to be J= -95
      cm(-1) at the DDCI level. The environmental electronic polarization is taken into
      account self-consistently using the individual polarizabilities of the atoms in a
      finite block of the crystal lattice (Discrete Reaction Field, DRF) and accounts
      for less than 5% of the calculated J value in TTTA. Furthermore, taking advantage
      of the chemical flexibility of the verdazyl radical family, the contribution of
      strong electron-withdrawing groups is analysed by extracting the J, U, t and K
      parameters from pairs of substituted verdazyl-based radicals. Our ab initio
      calculations of verdazyl radical pairs suggest that the addition of NO2 groups
      cause (i) the variations of the ferromagnetic and antiferromagnetic contributions
      to cancel out, leaving an almost constant exchange coupling constant, ca. J~ 20
      cm(-1), and that (ii) enhanced conduction properties can be anticipated. In
      contrast to inorganic analogues, one may conclude that the magnetic behaviour of
      neutral organic radical-based materials is mostly governed by the supramolecular
      arrangement, whereas environmental effects have a lesser impact.

PMID- 23552726
TI  - Effect of recombinant alpha1-antitrypsin Fc-fused (AAT-Fc)protein on the
      inhibition of inflammatory cytokine production and streptozotocin-induced
      diabetes.
AB  - alpha1-Antitrypsin (AAT) is a member of the serine proteinase inhibitor family
      that impedes the enzymatic activity of serine proteinases, including human
      neutrophil elastase, cathepsin G and neutrophil proteinase 3. Here, we expressed
      recombinant AAT by fusing the intact AAT gene to the constant region of IgG1 to
      generate soluble recombinant AAT-Fc protein. The recombinant AAT-Fc protein was
      produced in Chinese hamster ovary (CHO) cells and purified using mini-protein A
      affinity chromatography. Recombinant AAT-Fc protein was tested for
      antiinflammatory function and AAT-Fc sufficiently suppressed tumor necrosis
      factor (TNF)-alpha-induced interleukin (IL)-6 in human peripheral blood
      mononuclear cells (PBMCs) and inhibited cytokine-induced TNFalpha by different
      cytokines in mouse macrophage Raw 264.7 cells. However, AAT-Fc failed to suppress
      lipopolysaccharide-induced cytokine production in both PBMCs and macrophages. In
      addition, our data showed that AAT-Fc blocks the development of hyperglycemia in
      a streptozotocin-induced mouse model of diabetes. Interestingly, we also found
      that plasma-derived AAT specifically inhibited the enzymatic activity of elastase
      but that AAT-Fc had no inhibitory effect on elastase activity.

PMID- 23552728
TI  - Bruns nystagmus in cerebellopontine angle tumor.

PMID- 23552729
TI  - A dual channel optical detector for trace water chemodosimetry and imaging of
      live cells.
AB  - A novel 3-5-dichlorosalicylaldehyde Schiff base chemodosimeter (compound 1) for
      water is designed and synthesized, and it works based on a water-triggered
      reaction of a Schiff base. Addition of trace amounts of water into 1 in various
      organic solvents leads to a fluorescence turn-on response and a simultaneous dual
      channel signal modulation (both in the fluorescence and absorption spectra).
      Especially, 1 is found to be an outstanding fluorescence enhancement water sensor
      in methanol with an extremely low detection limit of 22 ppm. Consequently this
      probe can be utilized to detect trace water in commercial methanol. The
      quantitative detection of a wide range of water content is enhanced in THF and
      acetonitrile (0-35% v/v for THF and 0-20% v/v for acetonitrile), where the
      fluorescence peak intensity is nearly proportional to the amount of water added.
      Moreover, 1 can be used for monitoring pH through a novel ON-OFF-ON type signal
      modulation both in fluorescence and absorption spectra within a wide pH detection
      range. Thus, the chemodosimeter can not only be utilized to monitor the
      intracellular pH fluctuations, but also to accomplish simultaneous in situ
      staining of the cytosol and acidic organelles in two different channels,
      respectively.

PMID- 23552730
TI  - Trends and disparities in total-body skin examination: evaluating the National
      Health Interview Survey, 2000-2010.

PMID- 23552731
TI  - Fecal pathogen pollution: sources and patterns in water and sediment samples from
      the upper Cook Inlet, Alaska ecosystem.
AB  - Fecal pathogens are transported from a variety of sources in multi-use ecosystems
      such as upper Cook Inlet (CI), Alaska, which includes the state's urban center
      and is highly utilized by humans and animals. This study used a novel water
      quality testing approach to evaluate the presence and host sources of potential
      fecal pathogens in surface waters and sediments from aquatic ecosystems in upper
      CI. Matched water and sediment samples, along with effluent from a municipal
      wastewater treatment facility, were screened for Salmonella spp., Vibrio spp.,
      Cryptosporidium spp., Giardia spp., and noroviruses. Additionally, Bacteroidales
      spp. for microbial source tracking, and the fecal indicator bacteria Enterococcus
      spp. as well as fecal coliforms were evaluated. Overall, Giardia and Vibrio were
      the most frequently detected potential pathogens, followed by Cryptosporidium and
      norovirus, while Salmonella was not detected. Sample month, matrix type, and
      recent precipitation were found to be significant environmental factors for
      protozoa or host-associated Bacteroidales marker detection, whereas location and
      water temperature were not. The relative contribution of host-associated markers
      to total fecal marker concentration was estimated using a Monte Carlo method,
      with the greatest relative contribution to the Bacteroidales marker concentration
      coming from human sources, while the remainder of the universal fecal host source
      signal was uncharacterized by available host-associated assays, consistent with
      wildlife fecal sources. These findings show how fecal indicator and pathogen
      monitoring, along with identifying contributing host sources, can provide
      evidence of coastal pathogen pollution and guidance as to whether to target human
      and/or animal sources for management.

PMID- 23552732
TI  - Regeneration and recombination kinetics in cobalt polypyridine based dye
      sensitized solar cells, explained using Marcus theory.
AB  - Regeneration and recombination kinetics was investigated for dye-sensitized solar
      cells (DSCs) using a series of different cobalt polypyridine redox couples, with
      redox potentials ranging between 0.34 and 1.20 V vs. NHE. Marcus theory was
      applied to explain the rate of electron transfer. The regeneration kinetics for a
      number of different dyes (L0, D35, Y123, Z907) by most of the cobalt redox
      shuttles investigated occurred in the Marcus normal region. The calculated
      reorganization energies for the regeneration reaction ranged between 0.59 and
      0.70 eV for the different organic and organometallic dyes investigated. Under the
      experimental conditions employed, the regeneration efficiency decreased when
      cobalt complexes with a driving force for regeneration of 0.4 eV and less were
      employed. The regeneration efficiency was found to depend on the structure of the
      dye and the concentration of the redox couples. [Co(bpy-pz)2](2+), which has a
      driving force for regeneration of 0.25 eV for the triphenylamine based organic
      dye, D35, was found to regenerate 84% of the dye molecules, when a high
      concentration of the cobalt complex was used. Recombination kinetics between
      electrons in TiO2 and cobalt(iii) species in the electrolyte was also studied
      using steady state dark current measurements. For cobalt complexes with highly
      positive redox potentials (>0.55 V vs. NHE) dark current was found to decrease,
      consistent with electron transfer reactions occurring in the Marcus inverted
      region. However, for the cobalt complexes with the most positive redox potentials
      an increase in dark current was found, which can be attributed to recombination
      mediated by surface states.

PMID- 23552733
TI  - Strong EGFR signaling in cell line models of ERBB2-amplified breast cancer
      attenuates response towards ERBB2-targeting drugs.
AB  - Increasing the efficacy of targeted cancer therapies requires the identification
      of robust biomarkers suitable for patient stratification. This study focused on
      the identification of molecular mechanisms causing resistance against the anti
      ERBB2-directed therapeutic antibodies trastuzumab and pertuzumab presently used
      to treat patients with ERBB2-amplified breast cancer. Immunohistochemistry and
      clinical data were evaluated and yielded evidence for the existence of ERBB2
      amplified breast cancer with high-level epidermal growth-factor receptor (EGFR)
      expression as a separate tumor entity. Because the proto-oncogene EGFR tightly
      interacts with ERBB2 on the protein level, the hypothesis that high-level EGFR
      expression might contribute to resistance against ERBB2-directed therapies was
      experimentally validated. SKBR3 and HCC1954 cells were chosen as model systems of
      EGFR-high/ERBB2-amplified breast cancer and exposed to trastuzumab, pertuzumab
      and erlotinib, respectively, and in combination. Drug impact was quantified in
      cell viability assays and on the proteomic level using reverse-phase protein
      arrays. Phosphoprotein dynamics revealed a significant downregulation of AKT
      signaling after exposure to trastuzumab, pertuzumab or a coapplication of both
      antibodies in SKBR3 cells but no concomitant impact on ERK1/2, RB or RPS6
      phosphorylation. On the other hand, signaling was fully downregulated in SKBR3
      cells after coinhibition of EGFR and ERBB2. Inhibitory effects in HCC1954 cells
      were driven by erlotinib alone, and a significant upregulation of RPS6 and RB
      phosphorylation was observed after coincubation with pertuzumab and trastuzumab.
      In summary, proteomic data suggest that high-level expression of EGFR in ERBB2
      amplified breast cancer cells attenuates the effect of anti-ERBB2-directed
      antibodies. In conclusion, EGFR expression may serve as diagnostic and predictive
      biomarker to advance personalized treatment concepts of patients with ERBB2
      amplified breast cancer.

PMID- 23552734
TI  - Methylation profile of triple-negative breast carcinomas.
AB  - Breast cancer is a group of clinically, histopathologically and molecularly
      heterogeneous diseases, with different outcomes and responses to treatment.
      Triple-negative (TN) breast cancers are defined as tumors that lack the
      expression of estrogen receptor, progesterone receptor and epidermal growth
      factor receptor 2. This subgroup accounts for 15% of all types of breast cancer
      and its prevalence is higher among young African, African-American and Latino
      women. The hypermethylation of CpG islands (CpGI) is a common epigenetic
      alteration for suppressing gene expression in breast cancer and has been shown to
      be a key factor in breast carcinogenesis. In this study we analyzed the
      hypermethylation of 110 CpGI within 69 cancer-related genes in TN tumors. For the
      methylation analysis, we used the methyl-specific multiplex-ligation probe
      amplification assay. We found that the number of methylated CpGI is similar
      between TN and non-TN tumors, but the methylated genes between the groups are
      different. The methylation profile of TN tumors is defined by the methylation of
      five genes (that is, CDKN2B, CD44, MGMT, RB and p73) plus the non-methylation of
      11 genes (that is, GSTP1, PMS2, MSH2, MLH1, MSH3, MSH6, DLC1, CACNA1A, CACNA1G,
      TWIST1 and ID4). We conclude that TN tumors have a specific methylation profile.
      Our findings give new information for better understanding tumor etiology and
      encourage future studies on potential drug targets for triple-negative breast
      tumors, which now lack a specific treatment.

PMID- 23552735
TI  - Genome-wide profiling reveals transcriptional repression of MYC as a core
      component of NR4A tumor suppression in acute myeloid leukemia.
AB  - Acute myeloid leukemias (AMLs) are a heterogeneous group of diseases that are
      sustained by relatively rare leukemia-initiating cells (LICs) that exhibit
      diverse genetic and phenotypic properties. AML heterogeneity presents a major
      challenge to development of targeted therapies, and effective treatment will
      require targeting of common molecular drivers of AML maintenance. The orphan
      nuclear receptors NR4A1 and NR4A3 are potent tumor suppressors of AML. They are
      silenced in all human AML LICs, irrespective of patient cytogenetics, and their
      deletion in mice leads to postnatal AML development. In the current report, we
      address the tumor-suppressive mechanisms and therapeutic potential of NR4As for
      AML intervention. We show that rescue of either NR4A1 or NR4A3 inhibits the
      leukemogenicity of AML cells in vivo and reprograms a subset of gene signatures
      that distinguish primary human LICs from normal hematopoietic stem cells (HSCs),
      irrespective of subtype. Central to NR4A reprogramming is the acute suppression
      of an LIC submodule that includes the transcriptional repression of MYC.
      Additionally, we show that upregulation of MYC is an acute preleukemic
      consequence of NR4A deletion and that MYC suppression functionally contributes to
      NR4A antileukemic effects. Collectively, these results identify NR4As as novel
      targets for AML therapeutic intervention and reveal molecular targets of NR4A
      tumor suppression, including the suppression of MYC.

PMID- 23552736
TI  - Overexpression of ETV4 is oncogenic in prostate cells through promotion of both
      cell proliferation and epithelial to mesenchymal transition.
AB  - The discovery of translocations that involve one of the genes of the ETS family
      (ERG, ETV1, ETV4 and ETV5) has been a major advance in understanding the
      molecular basis of prostate cancer (PC). Each one of these translocations results
      in deregulated expression of one of the ETS proteins. Here, we focus on the
      mechanism whereby overexpression of the ETV4 gene mediates oncogenesis in the
      prostate. By siRNA technology, we show that ETV4 inhibition in the PC3 cancer
      cell line reduces not only cell mobility and anchorage-independent growth, but
      also cell proliferation, cell cycle progression and tumor growth in a xenograft
      model. Conversely, ETV4 overexpression in the nonmalignant human prostate cell
      line (RWPE) increases anchorage-independent growth, cell mobility and cell
      proliferation, which is probably mediated by downregulation of p21, producing
      accelerated progression through the cell cycle. ETV4 overexpression is associated
      with changes in the pattern of E-cadherin and N-cadherin expression; the cells
      also become spindle-shaped, and these changes are characteristic of the so-called
      epithelial to mesenchymal transition (EMT). In RWPE cells overexpressing ETV4 EMT
      results from a marked increase in EMT-specific transcription factors such as
      TWIST1, SLUG1, ZEB1 and ZEB2. Thus, whereas ETV4 shares with the other ETS
      proteins (ERG, ETV5 and ETV1) a major role in invasiveness and cell migration, it
      emerges as unique in that it increases at the same time also the rate of
      proliferation of PC cells. Considering the wide spectrum in the clinical course
      of patients with PC, it may be highly relevant that ETV4 is capable of inducing
      most and perhaps all of the features that make a tumor aggressive.

PMID- 23552737
TI  - Selective growth inhibition by glycogen synthase kinase-3 inhibitors in
      tumorigenic HeLa hybrid cells is mediated through NF-kappaB-dependent GLUT3
      expression.
AB  - Carcinogenesis and cancer progression, driven by mutations in oncogenes and tumor
      suppressor genes, result in biological differences between normal and cancer
      cells in various cellular processes. Specific genes and signaling molecules
      involved in such cellular processes may be potential therapeutic targets of
      agents that specifically interact with the key factors in cancer cells. Increased
      glucose uptake is fundamental to many solid tumors and well associated with
      increases in glycolysis and the overexpression of glucose transporters (GLUTs)
      such as GLUT1 and GLUT3 at the plasma membrane. Here, we used cell-based
      screening to identify glycogen synthase kinase-3beta (GSK-3beta) inhibitors that
      selectively target GLUT3-expressing tumorigenic HeLa cell hybrids as compared
      with non-tumorigenic hybrids that express GLUT1 alone. The GSK-3 inhibitors as
      well as GSK-3beta RNAi suppressed GLUT3 expression at the level of transcription,
      leading to apoptosis. This suppression was associated with NF-kappaB in a p53
      independent manner. Furthermore, GSK-3 inhibitors exhibited a synergistic effect
      with anticancer agents such as adriamycin and camptothecin in GULT3
      overexpressing colon cancer cells, but little effect in non-producing A431 cells.
      These results suggest a potential use of GSK-3 inhibitors to selectively kill
      cancer cells that overexpress GLUT3.

PMID- 23552738
TI  - PEA-15 unphosphorylated at both serine 104 and serine 116 inhibits ovarian cancer
      cell tumorigenicity and progression through blocking beta-catenin.
AB  - Ovarian cancer is a major cause of death among women; there remains an urgent
      need to develop new effective therapies to target this cancer. Phosphoprotein
      enriched in astrocytes (PEA-15) is a 15-kDa phosphoprotein that is known to bind
      ERK1/2, thus blocking cell proliferation. The physiological activity of PEA-15 is
      dependent on the phosphorylation status of serine 104 (Ser104) and Ser116.
      However, little is known about the impact of PEA-15 phosphorylation on tumor
      progression. We have previously shown that overexpression of PEA-15 has an
      antitumor effect against both breast and ovarian cancer cells. Here, we report
      that using a human ovarian cancer tissue microarray, we found that tissues from
      patients with ovarian cancer were significantly more likely than adjacent normal
      tissues to express PEA-15 phosphorylated at both sites. Using phosphomimetic and
      nonphosphorylatable mutants of PEA-15, we found that mutant double
      unphosphorylated PEA-15 in which Ser104 and Ser116 were substituted with alanine
      (PEA-15-AA) had a more potent antitumorigenic effect in ovarian cancer than did
      phosphomimetic PEA-15 in which Ser104 and Ser116 were substituted with aspartic
      acid (PEA-15-DD). Further, we observed that the antitumorigenic effect of PEA-15
      AA was a result of inhibition of the migration capacity of cells and inhibition
      of in vivo angiogenesis. This inhibition was partially dependent on inhibition of
      beta-catenin expression and nuclear translocalization. Taken together, our
      results suggest that phosphorylated PEA-15 is an important contributor to the
      aggressiveness of ovarian cancer and justify the development of PEA-15-AA as an
      effective therapeutic molecule in the treatment of ovarian cancer.

PMID- 23552739
TI  - Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker
      for hepatocellular carcinoma.
AB  - Cyclooxygenases (COX-1 and 2) catalyze the first step in prostanoid biosynthesis.
      They are implicated in homeostatic processes with an important role in
      inflammation and carcinogenesis. In the liver, COX-2 expression is restricted to
      proliferation or dedifferentiation situations. The COX-2 promoter contains
      numerous CpG islands that, when hypermethylated, result in transcriptionally
      silencing thus regulating the growth of carcinoma cells. In this work, we
      investigated whether a correlation exists between COX-2 expression and
      methylation signatures at the 5'region of the gene in hepatoma cell lines and
      human hepatocellular carcinoma (HCC). We also examined the acetylation status of
      the COX-2 promoter and the effects of histone deacetylase (HDAC) inhibitors on
      COX-2 expression. Our results suggest a significant association between reduced
      COX-2 expression and promoter hypermethylation of COX-2 and histone deacetylation
      in some hepatoma cell lines and in HCC. Treatment with demethylating agents or
      HDAC inhibitors restored the expression of COX-2. Moreover, in an HCC cohort, a
      statistically significant inverse association was observed between COX-2 mRNA
      levels and promoter methylation. In agreement with these data, a reduction of
      overall survival of the patients was observed after decreased COX-2 expression by
      promoter hypermethylation and histone H3 hypoacetylation.

PMID- 23552740
TI  - Stability and physical properties of a tri-ring based porous g-C4N3 sheet.
AB  - Due to their porosity and biocompatibility, C-N based graphitic sheets are
      currently attracting much attention. Here we present our findings on a new
      structure of a g-C4N3 sheet composed of the tri-ring heptazine-like units, which
      is energetically more stable, more elastic and isotropic than the previously
      proposed structure consisting of the single-ring triazines. Dynamics and thermal
      stability of the new structure are confirmed using phonon spectrum calculations
      and molecular dynamics simulations. Based on hybrid density functional theory, we
      demonstrate that the tri-ring unit based g-C4N3 is a semiconductor with a small
      band gap, sharp optical absorption peaks and high absorption intensity. Although
      the new structure is nonmagnetic, ferromagnetism can be introduced and the
      optical absorption can be tuned by applying a small strain.

PMID- 23552741
TI  - Prolonged antibiotic treatment in long-term care: role of the prescriber.
AB  - IMPORTANCE: Given that most common bacterial infections can be treated with
      antibiotic courses of 7 or fewer days, reducing standard antibiotic treatment
      durations may be an avenue to curtailing antibiotic overuse in long-term care.
      OBJECTIVES: To describe the variability in the duration of antibiotic treatment
      courses in long-term care across resident recipients and prescribing physicians
      and to determine whether this variability is influenced by prescriber preference.
      DESIGN AND SETTING: Province-wide retrospective analysis of residents of Ontario,
      Canada, long-term care facilities in 2010. PARTICIPANTS: All adults aged 66 years
      or older who received an incident treatment course with a systemic antibiotic
      while residing in an Ontario long-term care facility. MAIN OUTCOME MEASURE:
      Antibiotic treatment duration was examined across residents and prescribing
      physicians. The proportion of a physician's treatment courses that exceeded 7
      days was used to classify short-, average-, and long-duration prescribers.
      RESULTS: Of 66 901 long-term care residents from 630 long-term care facilities,
      50 061 (77.8%) received an incident antibiotic treatment course (with 51 540
      antibiotic courses prescribed). The most commonly selected antibiotic treatment
      course was 7 days (in 21 136 courses [41.0%]), but 23 124 (44.9%) exceeded 7
      days. Among the 699 physicians responsible for 20 or more antibiotic treatment
      courses, the median (interquartile range) proportion of treatment courses beyond
      7 days was 43.5% (26.9%-62.9%) (range, 0%-97.1%). Twenty-one percent of
      prescribers had a higher-than-expected proportion of prescriptions beyond the 7
      day threshold. Patient characteristics were similar across short-, average-, and
      long-duration prescribers. A mixed logistic model confirmed that prescribers were
      an important determinant of treatment duration (P < .001), with a relative odds
      of prolonged prescription of 3.84 for 75th vs 25th percentile prescribers.
      CONCLUSIONS AND RELEVANCE: Antibiotic treatment courses in long-term care
      facilities are often prescribed for long durations, and this appears to be
      influenced by prescriber preference more than patient characteristics. Future
      trials should evaluate antibiotic stewardship interventions targeting prescriber
      preferences to systematically shorten average treatment durations to reduce the
      complications, costs, and resistance associated with antibiotic overuse.

PMID- 23552742
TI  - The role of hepcidin-25 in kidney transplantation.
AB  - BACKGROUND: Hepcidin-25 is a peptide hormone involved in iron absorption and
      homeostasis and found at increased serum levels in conditions involving systemic
      inflammation, renal dysfunction, and increased adiposity. Hepcidin may play a
      role in the pathogenesis of anemia, but its role in kidney transplantation is
      undefined. METHODS: This study enrolled 100 stable patients beyond 12 months
      after transplantation, from a large single United Kingdom center. Serum hepcidin
      25 level, and relevant demographic and laboratory data pertinent to
      posttransplantation anemia, were measured and collected. Independent predictors
      of serum hepcidin were evaluated, and the relationship between hepcidin and
      hemoglobin, assessed. RESULTS: Independent associations were seen between higher
      hepcidin levels and allograft dysfunction (estimated glomerular filtration rate),
      increased inflammation (high-sensitivity C-reactive peptide), higher transferrin
      saturation (a marker of iron stores), and the use of marrow-suppressive
      medication (P<0.05 for all). Higher fat tissue index (whole-body multifrequency
      bioimpedance measurement) was also associated with higher hepcidin levels, but
      this relationship did not persist after adjustment for inflammation (high
      sensitivity C-reactive peptide). In turn, inflammation was associated with
      increased fat tissue index (P=0.01) and male gender (P=0.04). A nonlinear
      association between serum hepcidin level and hemoglobin was seen, with a
      progressive fall in hemoglobin as hepcidin levels rose to 100 ng/mL, but little
      effect thereafter (P=0.009). This association was independent of renal
      dysfunction and female gender, both of which were also independently associated
      with a lower hemoglobin level. CONCLUSIONS: These results highlight possible
      mechanisms of hemoglobin reduction in kidney transplantation patients, and the
      therapeutic opportunities from understanding the role of hepcidin in this
      context.

PMID- 23552744
TI  - General surgery residency after graduation from U.S. medical schools: visa
      related challenges for the international citizen.
AB  - International-United States medical graduates (I-USMGs) are non-US citizen
      graduates of U.S. medical schools. Although academically equivalent to US-citizen
      peers, they are subject to the same visa requirements as non-US citizen
      international medical graduates. We hypothesized that visa sponsorship policies
      of general surgery programs (GSPs) may be discordant with the enrollment patterns
      of I-USMGs. A total of 196 GSPs participated in a telephone survey regarding visa
      sponsorship policies. Whereas GSPs preferred J-1 to H-1B sponsorship (64.2% vs.
      32.6%), I-USMG enrollment favored programs supporting H-1B sponsorship (72.1% vs.
      7.5%) (P = .01). University-affiliated programs were more likely to sponsor H1-Bs
      than independent programs (39.6% vs. 24.4%) (P = .03) and trained a greater
      proportion of I-USMGs than independent programs (40.6% vs. 14.0%) (P < .01).
      Restrictive policies against H-1B sponsorship may limit GSPs' I-USMG applicant
      pool and restrict I-USMGs' surgical training options.

PMID- 23552743
TI  - Stem cell marker nestin is critical for TGF-beta1-mediated tumor progression in
      pancreatic cancer.
AB  - The stem cell marker nestin is an intermediate filament protein that plays an
      important role in cell integrity, migration, and differentiation. Nestin
      expression occurs in approximately one third of pancreatic ductal adenocarcinoma
      (PDAC), and its expression strongly correlates with tumor staging and metastasis.
      Little is known about the mechanisms by which nestin influences PDAC progression.
      Here, nestin overexpression in PDAC cells increased cell motility and drove
      phenotypic changes associated with the epithelial-mesenchymal transition (EMT) in
      vitro; conversely, knockdown of endogenous nestin expression reduced the
      migration rate and reverted cells to a more epithelial phenotype. Mouse xenograft
      studies showed that knockdown of nestin significantly reduced tumor incidence and
      volume. Nestin protein expression was associated with Smad4 status in PDAC cells;
      hence, nestin expression might be regulated by the TGF-beta1/Smad4 pathway in
      PDAC. We examined nestin expression after TGF-beta1 treatment in human pancreatic
      cancer PANC-1 and PANC-1 shSmad4 cells. The TGF-beta1/Smad4 pathway induced
      nestin protein expression in PDAC cells in a Smad4-dependent manner. Moreover,
      increased nestin expression caused a positive feedback regulator of the TGF-beta1
      signaling system. In addition, hypoxia was shown to induce nestin expression in
      PDAC cells, and the hypoxia-induced expression of nestin is mediated by the TGF
      beta1/Smad4 pathway. Finally, the antimicrotubule inhibitors, cytochalasin D and
      withaferin A, exhibited anti-nestin activity; these inhibitors might be potential
      antimetastatic drugs. Our findings uncovered a novel role of nestin in regulating
      TGF-beta1-induced EMT. Anti-nestin therapeutics may serve as a potential
      treatment for PDAC metastasis.

PMID- 23552746
TI  - Structurally well-defined group 4 metal complexes as initiators for the ring
      opening polymerization of lactide monomers.
AB  - Polylactide (PLA) is an attractive polymeric material due to its origin from
      annually renewable resources and its biodegradability. The ring-opening
      polymerization (ROP) of lactide initiated by Lewis acidic and oxophilic metal
      based catalysts constitutes the method of choice to access PLA in a controlled
      and stereoselective manner. The design and synthesis of ligand-supported metal
      complexes to act as effective ROP initiators of lactide monomers have been the
      subject of numerous investigations over the past decades. In view of their
      oxophilic nature, well-defined group 4 metal complexes supported by polydentate
      supporting ligands have appeared as active initiators for lactide ROP. This
      perspective summarizes various classes of structurally well-defined group 4 metal
      initiators developed for lactide ROP. It also provides observed trends regarding
      their catalytic performance. Whenever appropriate and possible, catalyst
      structure-ROP performance (i.e. activity, control and stereoselectivity)
      relationships are rationalized.

PMID- 23552748
TI  - Management of melanoma in a patient population: using electronic health records
      to enhance postdiagnosis surveillance.

PMID- 23552749
TI  - [Expression and function of E prostanoid receptors in urological cancer].
AB  - The biological activities of prostaglandin E2 are mediated through their specific
      receptors, E prostanoid receptors (EPRs). This family comprises 4 subtypes (EP1R
      4R), and has been associated with cancer development and progression. In
      urological cancers, expression of EP2R and EP4R can be significant predictors of
      survival for renal cell carcinoma (RCC). On the other hand, EP1R, EP2R, and EP4R
      are known to be associated with carcinogenesis and malignant aggressiveness in
      prostate cancer. In addition, EP4R has been associated with tumor progression and
      prognosis in urothelial cancer of the upper urinary tract. There is a general
      agreement that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk
      of several malignancies including colorectal cancer. However, NSAIDs often cause
      gastrointestinal injury and nephropathy. On the other hand, cyclooxygenase (COX)
      2-selective inhibitors can reduce the progression of cancer via the suppression
      of cell proliferation angiogenesis without decreasing adverse reactions. However,
      COX-2-selective inhibitors might increase the risk of cardiovascular disease,
      including myocardial infarction. More selective and detailed control of COX-2
      mediated signals is thus needed to improve anti-tumor effects and to decrease
      adverse reactions. EPRs are expected to serve as new therapeutic targets in
      urological cancer, because they are more selective in malignant phenotypes.
      Finally, we speculate that some EPRs inhibitors may reduce adverse events and
      exert more intense effects on urological cancer.

PMID- 23552750
TI  - [Adrenal cortical adenoma with increased uptake of 18F-fluoro-deoxy-glucose on
      PET/CT suspected as an adrenal metastasis from the cervical cancer : a case
      report].
AB  - A 61-year-old woman was referred to our department with a diagnosis of left
      solitary adrenal metastasis from cervical cancer in September 2011. She presented
      with postmenopausal bleeding in September 2010. The patient received seven
      courses of paclitaxel (175 mg/m2) and carboplatin (6 mg/GFR+25) for stage IV
      cervical cancer with paraaortic, bilateral common iliac, mediastinal lymph node
      metastases and left adrenal metastasis from October 2010 to April 2011.
      Paraaortic radiation (50.4 Gy) was subsequently administered from May 2011 to
      July 2011. Abdominal nonenhanced computed tomography (CT) revealed a left 26*21
      mm adrenal mass with regular margins (attenuation values 53 HU). On enhanced CT,
      the mass showed heterogeneous enhancement. F fluoro-2-deoxy D-glucose (FDG)
      positron emission tomography/CT images showed moderately increased FDG-avid
      uptake in the left adrenal tumor which was high enough to be suspicious of
      malignant tumor (standardized uptake value max : SUVmax 6.8). There were no other
      foci of pathologic uptake of FDG in the whole body. The plasma endocrinological
      examinations was all normal. Left laparoscopic adrenalectomy was performed. The
      final pathologic evaluation revealed adrenal cortical adenoma.

PMID- 23552751
TI  - [A case of myocardiac metastasis of clear cell renal carcinoma successfully
      treated with sunitinib].
AB  - A 65-year-old male was referred to our clinic from orthopedics because his right
      gastrocnemius muscle tumor was diagnosed as a metastatic renal cell carcinoma
      (RCC) with clear cell/spindle cell morphology. He had right nephrectomy for RCC
      18 years previously. At 17 months following the first visit to our clinic, brain,
      lung and right gluteus medius muscle metastases were identified on positron
      emission tomography computed tomography (PET-CT). The echocardiogram for the
      evaluation of his heart function incidentally revealed a 3 cm nodular lesion in
      the right ventricular wall suggesting myocardiac metastasis. He started to take
      sunitinib at a standard dose of 50 mg/day. A subsequent echocardiogram during the
      2nd cycle of sunitinib showed complete disappearance of the myocardiac
      metastasis. After the 2nd cycle, PET-CT revealed a partial response (PR) for the
      other metastases. He received 8 cycles of sunitinib. The best response was PR,
      and progression-free survival was 6 months. After that, he took everolimus for 7
      months. Although the myocardiac metastasis continued to show a complete response
      during the treatment course, he died of progressive lung metastases at 21 months
      following the administration of sunitinib. Diagnosis of myocardiac metastasis of
      RCC during the treatment course as well as its successful treatment with
      molecular targeting agents has rarely been reported.

PMID- 23552752
TI  - [Hyperuricemia and acute kidney injury following kidney transplantation : a case
      report].
AB  - We report a case of hyperuricemia and acute kidney injury associated with
      mizoribine (MZR). A 15- year-old male with congenital renal hypoplasia underwent
      kidney transplantation. We used tacrolimus extended release (0.15 mg/kg/day),
      mizoribine (MZR) (12 mg/kg/day), prednisolone and basiliximab as
      immunosuppressants. On the 35th post operative day, he complained of acute right
      chest pain, right inguinal pain and dyspnea. Serum uric acid and creatinine were
      elevated. Accordingly, we changed MZR to mycophenolate mofetil, and added
      allopurinol and potassium citrate. Gradually, the symptoms disappeared and renal
      function was improved. In this case, prolonged MZR metabolism, hyperuricemia and
      progressive renal dysfunction may have formed a vicious cycle. In conclusion,
      monitoring of serum uric acid level is necessary, especially when using a high
      dose MZR.

PMID- 23552753
TI  - [A case of mucinous tubular and spindle cell carcinoma of the kidney].
AB  - Mucinous tubular and spindle cell carcinoma (MTSCC) is a distinct entity in the
      World Health Organization classification of kidney tumors since 2004. Herein, we
      report a case of a patient with MTSCC of the kidney. A 48-year-man visited our
      hospital with a chief complaint of occult blood in his urine, confirmed by urine
      occult blood reaction. Computed tomography revealed a solid tumor in the right
      kidney. The tumor was 40*38 mm in length and was slightly enhanced (cT1aN0M0).
      Therefore, we performed radical nephrectomy. On analysis of the resected
      specimen, we found that the number of comparatively small malignant cells had
      increased markedly, forming branched tubular cuboidal cells. Further more,
      positive results were obtained on staining the stroma with both PAS and alcian
      blue stains characteristic of papillary renal cell carcinoma ; however,
      extracellular mucinous material was found to be depleted. Therefore, we needed to
      differentiate between papillary renal cell carcinoma and MTSCC. Finally, on the
      basis of the immunohistochemical staining results-vimentin (+), CK34betaE12 (-),
      and CD10 (-)-MTSCC was confirmed.

PMID- 23552754
TI  - [Breast cancer metastasized to the pararenal fat 26 years after mastectomy : a
      case report].
AB  - A 66-year-old woman was referred to our hospital with a right renal tumor in
      October 2010. In 1984, she underwent a mastectomy because of left breast cancer.
      In 2006, she underwent a lobectomy because of right lung cancer. A follow-up
      computed tomography of the lung cancer revealed a right renal tumor which
      extended to the right quadratus lumborum muscle. An exploratory laparotomy was
      performed and the tumor was found to be malignant by an intra-operative
      examination. Then, we performed a right radical nephrectomy together with the
      excision of quadratus lumborum muscle. Pathological examination revealed breast
      cancer metastasized to the pararenal fat. We could not find any invasion of the
      tumor into the renal parenchyma. We followed her for 2 months after the operation
      without any evidence of recurrence, but she suddenly expired due to an unrelated
      accident.

PMID- 23552755
TI  - [Urothelial carcinoma after renal transplantation : a case report].
AB  - We report a case of urothelial carcinoma (UC) in a 69-year-old man that occurred
      after renal transplantation. He had started receiving hemodialysis therapy in
      2004 due to diabetic nephropathy and underwent living related renal
      transplantation from his brother in 2005. He was referred to our hospital in May
      2009 with asymptomatic microscopic hematuria. Cystoscopy findings revealed
      multiple bladder tumors, and transurethral resection of bladder tumor (TUR-BT)
      followed by intravesical instillation of pirarubicin was performed.
      Histopathological findings revealed UC (G1>G2, pTa). Cytology findings after the
      operation did not become negative; urine specimen from the native right ureter
      was positive, and abdominal computed tomography (CT) demonstrated a right pelvic
      tumor. In January 2010, a laparoscopic right nephroureterectomy was performed and
      pathological examination findings revealed UC in the right pelvis (G3>G2,
      INFbeta, pT3). In March 2010, recurrence of the bladder tumor was demonstrated as
      carcinoma in situ (CIS) of the bladder and left native ureter. In June 2010, a
      radical cystectomy with left nephroureterectomy and ileal conduit diversion were
      performed. One week after that operation, laboratory results revealed abnormal
      hepatic function and CT showed multiple liver metastases. The patient died in
      August 2010, 2 months after surgery.

PMID- 23552756
TI  - [A case of inverted papilloma of the renal pelvis, associated with metachronous
      urothelial carcinoma of the urinary bladder].
AB  - The patient visited our hospital because of macrohematuria. Cystoscopical
      examination did not reveal any bladder tumors but a tumor shadow in the right
      renal pelvis was revealed by computed tomographic scan. Urothelial carcinoma was
      suspected and right nephroureterectomy was performed. Pathologically the tumor
      was diagnosed as inverted papilloma. Four months later during the follow up of
      the tumor, urothelial carcinoma of the urinary bladder was detected by
      cystoscopy. Inverted papilloma of the renal pelvis is a rare lesion and only 39
      cases to date have been reported. Because inverted papilloma of the upper urinary
      tract is often associated with other urothelial tumors, careful long-term follow
      up is advisable.

PMID- 23552757
TI  - [Pseudosarcomatous myofibroblastic proliferation of the bladder-case report].
AB  - A 66-year-old man with a history of sporadic von Recklinghausen' s disease was
      treated for pseudosarcomatous myofibroblastic proliferation in the bladder. The
      patient had a history of repetitive recurrence of bladder carcinoma requiring
      transurethral resection (TUR) 4 times and 1 course of intravesical BCG
      instillation. Three months after the fourth TUR, an intravesical solid mass 4 cm
      in diameter was detected. Suspicion of recurrent bladder carcinoma led to a fifth
      TUR procedure. Pathological findings showed submucosal growth of myofibroblasts
      with myxoidal stroma and we made a diagnosis of Pseudosarcomatous myofibroblastic
      proliferation. The patient was well with no evidence of recurrence after 1 year.

PMID- 23552758
TI  - [A case of bladder cancer with metastasis to the bone of the hand].
AB  - Metastasis to the bone of the hand is rare. In addition, metastasis to the bone
      of the hand from bladder cancer is extremely rare. We herein report a case of
      distal phalanx metastasis from bladder cancer. A 64- year-old man who was
      diagnosed with bladder cancer (cT2bN0M0) received total cystectomy (pT3bN2). Two
      months after the surgery, a roentgenogram revealed lung metastasis. Then we
      administered 2 cycles of chemotherapy using gemcitabine and cisplatin. Computed
      tomography revealed a partial response. However, several months after
      chemotherapy, we noted that his left ring finger was swollen and showed erythema.
      We made a diagnosis of metastasis to the distal phalanx of the left ring finger
      and amputated the finger. Pathological findings showed no conflict with
      metastasis from bladder cancer. Postoperative course was good, but he died about
      three months after the diagnosis of metastasis.

PMID- 23552759
TI  - [Urethral condyloma acuminata in an elderly patient : a case report].
AB  - A 76-year-old man presented to our hospital with asymptomatic bleeding of the
      urethra. Endoscopic examination showed multiple urethral papillary tumors in the
      pendulous urethra, and the tumors were surgically resected. Histopathological
      examination indicated urethral condyloma acuminata, and the results of a
      polymerase chain reaction-based invader assay using urethral swabs taken after
      surgery suggested low risk human papilloma virus infection. This is a relatively
      rare case because urethral condyloma acuminata has been reported in only a few
      elderly patients so far. No obvious recurrence of condyloma acuminata has been
      observed for 18 months after surgery.

PMID- 23552760
TI  - [A case of stromal tumors of uncertain malignant potential treated by radical
      prostatectomy].
AB  - A 56-year-old man visited a local hospital after experiencing urinary frequency
      for five years. A digital rectal examination revealed a markedly enlarged
      prostate and his serum prostate specific antigen (PSA) was 9.0 ng/ml. Although
      the first transrectal biopsy could not determine the final diagnosis due to
      insufficient sampling, the additional biopsy revealed prostatic stromal tumor of
      uncertain malignant potential. Magnetic resonance imaging and computed tomography
      showed an organ-confined huge prostate tumor. We performed radical prostatectomy
      uneventfully and the specimen weighed 141 g. One year after the operation, the
      patient had no urinary symptoms and no evidence of disease recurrence.

PMID- 23552761
TI  - [A case report of eosinophilic funiculitis difficult to distinguish from
      incarceration of inguinal hernia].
AB  - A 45-year-old man visited our emergency room with left inguinal pain, mass and
      high-grade fever. Emergency surgery was performed with a primary diagnosis of
      left inguinal hernia. Although there was no hernia, there was a mass involving
      the spermatic cord in the left inguinal canal. We performed high orchiectomy
      because of the possibility of malignancy. Pathological findings showed
      eosinophilic infiltration in the mass lesion. An allergic inflammation was
      suspected to have occurred in the spermatic cord. His postoperative course was
      good.

PMID- 23552762
TI  - ACP Journal Club. Hydroxyethyl starch 130/0.4 and saline did not differ for
      mortality at 90 days in ICU patients.

PMID- 23552763
TI  - Clinical predictors of urgent findings on abdominopelvic CT in emergency
      department patients with Crohn's disease.
AB  - BACKGROUND: Patients with Crohn's disease (CD) are frequently exposed to
      diagnostic radiation in emergency departments (EDs). We aimed to examine clinical
      predictors of urgent abdominopelvic computed tomography (APCT) findings in this
      population. METHODS: A retrospective cross-sectional study was performed among
      adults with CD presenting to 2 emergency departments with a gastrointestinal
      chief complaint. The outcome, APON (abscess, perforation, obstruction, new or
      worsening non-CD-related findings), included APCTs with new or worsening CD
      related or non-CD-related urgent findings. Variables with P < 0.05 in bivariate
      analyses were included in a multivariable logistic regression model, which was
      also used to develop a risk score for APON. RESULTS: A total of 481 APCTs were
      performed and 166 (34.5%) identified APON. Variables retained in the final model
      were history of intestinal obstruction (odds ratio [OR]: 3.78, 95% confidence
      interval [CI]: 2.27-6.28), history of intraabdominal abscess (OR: 2.64, 95% CI:
      1.43 to 4.88), current hematochezia (OR: 0.38, 95% CI: 0.21 to 0.68), and white
      blood cell count >12,000/MUL (OR: 2.49, 95% CI: 1.63 to 3.84). The c-statistic
      was 0.72. The risk score subtracts 1 point for hematochezia, and adds 1 point for
      each of the other variables. Among patients with a risk score of -1, the
      predicted and observed risk for APON was 9% and 6%, respectively. Any score
      greater than -1 had a predicted and observed risk of 19.8% and higher.
      CONCLUSIONS: An APON risk score of -1 is associated with a low risk of urgent
      APCT findings in patients with CD in the emergency department. Implementation of
      such a tool may support clinical decision-making in the ED setting.

PMID- 23552764
TI  - The prevalence and outcome of jejunal lesions visualized by small bowel capsule
      endoscopy in Crohn's disease.
AB  - BACKGROUND: Small bowel capsule endoscopy is the most sensitive technique for the
      detection of lesions in the small intestine. The aims of the study were to assess
      the prevalence and clinical significance of jejunal lesions detected by small
      bowel capsule endoscopy in patients with an established Crohn's disease. RESULTS:
      One hundred and eight patients, including 32 patients with ileal disease, 25
      patients with colonic disease, and 51 patients with ileocolonic disease,
      underwent small bowel capsule endoscopy, and findings were analyzed
      retrospectively. Jejunal lesions were detected in 56% of these patients, of whom
      18 (17%) had lesions only in the jejunum. Jejunal lesions were less frequently
      detected (12% versus 38%, P = 0.001) when location of the disease was limited to
      the colon at ileocolonoscopy. Conversely, when Crohn's disease affected the
      ileum, jejunal lesions were more frequently detected (40% versus 17%, P = 0.007).
      During a median follow-up time of 24.0 months (interquartile, 8.0-46.2), 50
      clinical relapses occurred. The presence of jejunal lesions was the only
      independent factor associated with an increased risk of relapse (P = 0.02). In
      nonsmokers and in patients treated by immunosuppressors, the presence of jejunal
      lesions tended to increase the risk of relapse (P = 0.06 and 0.05, respectively).
      CONCLUSIONS: Jejunal lesions are detected in more than half of the patients with
      Crohn's disease. The prevalence of jejunal lesions is higher when the terminal
      ileum is involved and associated with an increased risk of further clinical
      relapse. It may be regarded as a factor of severity.

PMID- 23552765
TI  - Impact of current smoking on the clinical course of microscopic colitis.
AB  - BACKGROUND: Whether current smoking worsens the clinical course of microscopic
      colitis (MC) is unknown. The aim was to evaluate the impact of smoking on the
      clinical course of MC. METHODS: One hundred and eighty-four patients (72% women;
      age, 62.4 +/- 1.1 years) with MC (118 collagenous colitis (CC) and 66 lymphocytic
      colitis (LC) were evaluated (39 of them were current smokers). In all the
      patients, smoking habits and clinical data at presentation, response to therapy,
      and clinical relapses during follow-up were prospectively recorded. Risk factors
      for clinical relapse were studied in 160 patients after a mean follow-up of 28 +/
      1 months. Cox regression analysis was used to adjust for confounding variables.
      RESULTS: Age at diarrhea onset was 63.0 +/- 1.4 years in nonsmokers and 50.4 +/-
      2.1 years in current smokers (P < 0.001). There was no significant influence of
      smoking habit on either clinical symptoms at diagnosis or clinical remission
      rate. Clinical relapse rate was 25.5% for CC and 29.6% for LC, with the mean
      relapse-free time 28.8 months (95% confidence interval, 26.3-31.4) for CC and
      26.9 months (95% confidence interval, 26-30.3) for LC (P = 0.5). Multivariate
      analysis showed that age at diagnosis (<50 years versus others; adjusted hazard
      ratio, 2.8; 95% confidence interval, 1.3-6; P = 0.01) was associated with risk of
      relapse of CC but not LC. Current smoking was not an independent risk factor for
      either CC or LC relapse. CONCLUSIONS: Active smokers developed MC more than a
      decade before nonsmokers. Age at diagnosis, but not smoking, was an independent
      risk factor of relapse in patients with CC.

PMID- 23552766
TI  - Periappendiceal inflammation in pediatric ulcerative colitis.
AB  - BACKGROUND: An involvement of the appendiceal orifice as a distintive skip lesion
      in adults with left side ulcerative colitis (UC) has been reported. The aim of
      our prospective study was to evaluate, by endoscopy and histology, the prevalence
      of periappendiceal inflammation (PAI) in children affected by UC. METHODS: Fifty
      of 77 consecutive children undergoing total colonoscopy, who had a diagnosis of
      UC not extended beyond the hepatic flexure were enrolled. RESULTS: PAI was
      endoscopically present in 16 of 50 patients (32%) with UC. Patients were divided
      in 2 groups: group A included the 16 patients with PAI, whereas group B included
      34 patients without PAI. We found that among the 2 groups, PAI was more frequent
      in patients with new diagnosis than in those with pre-existing UC (P = 0.016). At
      index colonoscopy, the patients of group A had a significant major extent of
      disease (P = 0.013). Moreover, the histologic grade of inflammation at the
      ascending colon was significantly higher in group A than in group B (P = 0.014).
      Clinical activity, measured by pediatric ulcerative colitis activity index, and
      use of medication did not show significant differences among groups (P = 0.464
      and P = 0.723, respectively). The use of immunosuppressant was significantly
      higher in group A than in group B. CONCLUSIONS: PAI is a frequent skip lesion in
      children with UC. It seems more frequent in patients with new diagnosis, and it
      is associated with a major extent of the disease and with a higher grade of
      histologic inflammation at the ascending colon.

PMID- 23552767
TI  - Ten years of infliximab for Crohn's disease: outcome in 469 patients from 2
      tertiary referral centers.
AB  - BACKGROUND: Aim was to assess the long-term clinical efficacy of infliximab
      therapy in patients with Crohn's disease treated in a cohort of 2 tertiary
      referral centers in the Netherlands. METHODS: All consecutive patients with
      Crohn's disease treated with infliximab were assessed. Endpoints were primary
      clinical efficacy, sustained benefit, efficacy of retreatment, surgical
      intervention rates, and safety. Sustained benefit was determined by Kaplan-Meier
      analysis. The estimated 5-year benefit was calculated. RESULTS: A total of 469
      patients were included. Median follow-up length was 4.5 years (interquartile
      range, 2.7-6.8). Seventy patients (15%) had unsuccessful remission induction, and
      316 patients received maintenance therapy. Scheduled maintenance regimen was
      successful in 169 of 276 (61%). Episodic maintenance therapy was successful in 19
      of 40 patients (48%). Estimated 5-year sustained benefit was 55.7% (95%
      confidence interval, 48.8-62.6). Concomitant thiopurines were associated with
      improved sustained benefit. A second course of infliximab after previous
      discontinuation was prescribed in 131 patients with similar efficacy rates.
      Abdominal surgical intervention rate per 100 patient-years was significantly
      reduced after infliximab initiation in patients with a scheduled maintenance
      regime (reduction, 2.70; 95% confidence interval, -4.82 to -0.35; P = 0.018).
      Mortality and malignancy rates were 1.9% (0.39/100 patient-years) and 3.4%
      (0.70/100 patient-years), respectively. CONCLUSIONS: The present study shows an
      estimated 5-year sustained benefit of 55.7% in patients with Crohn's disease
      treated with infliximab maintenance therapy. Remission induction and maintenance
      were equally successful in patients starting infliximab and patients who
      temporarily stopped and were retreated. Long-term use of infliximab was safe and
      reduced the need for surgery in patients on scheduled maintenance therapy.

PMID- 23552769
TI  - Timing of surgical antibiotic prophylaxis and the risk of surgical site
      infection.
AB  - IMPORTANCE: Timing of prophylactic antibiotic administration for surgical
      procedures is a nationally mandated and publicly reported quality metric
      sponsored by the Centers for Medicare and Medicaid Services Surgical Care
      Improvement Project. Numerous studies have failed to demonstrate that adherence
      to the Surgical Care Improvement Project prophylactic antibiotic timely
      administration measure is associated with decreased surgical site infection
      (SSI). OBJECTIVE; To determine whether prophylactic antibiotic timing is
      associated with SSI occurrence. DESIGN: Retrospective cohort study using national
      Veterans Affairs patient-level data on prophylactic antibiotic timing for
      orthopedic, colorectal, vascular, and gynecologic procedures from 2005 through
      2009. SETTING: National Veterans Affairs Surgical Care Improvement Project data
      from 112 Veterans Affairs hospitals and matched Veterans Affairs Surgical Quality
      Improvement Program data. PATIENTS: Patients undergoing hip or knee arthroplasty,
      colorectal surgical procedures, arterial vascular surgical procedures, and
      hysterectomy. INTERVENTION: Timing of prophylactic antibiotic administration with
      respect to surgical incision time. MAIN OUTCOMES AND MEASURES: Data for
      prophylactic antibiotic agent, prophylactic antibiotic timing with respect to
      surgical incision, and patient and procedure risk variables were assessed for
      their relationship with the occurrence of a composite superficial or deep
      incisional SSI within 30 days after the procedure. Nonlinear generalized additive
      models were used to examine the association between antibiotic timing and SSI.
      RESULTS: Of the 32,459 operations, prophylactic antibiotics were administered at
      a median of 28 minutes (interquartile range, 17-39 minutes) prior to surgical
      incision, and 1497 cases (4.6%) developed an SSI. Compared with procedures with
      antibiotic administration within 60 minutes prior to incision, higher SSI rates
      were observed for timing more than 60 minutes prior to incision (unadjusted odds
      ratio [OR] = 1.34; 95% CI, 1.08-1.66) but not after incision (unadjusted OR =
      1.26; 95% CI, 0.92-1.72). In unadjusted generalized additive models, we observed
      a significant nonlinear relationship between prophylactic antibiotic timing and
      SSI when considering timing as a continuous variable (P = .01). In generalized
      additive models adjusted for patient, procedure, and antibiotic variables, no
      significant association between prophylactic antibiotic timing and SSI was
      observed. Vancomycin hydrochloride was associated with higher SSI occurrence for
      orthopedic procedures (adjusted OR = 1.75; 95% CI, 1.16-2.65). Cefazolin sodium
      and quinolone in combination with an anaerobic agent were associated with fewer
      SSI events (cefazolin: adjusted OR = 0.49; 95% CI, 0.34-0.71; quinolone: adjusted
      OR = 0.55; 95% CI, 0.35-0.87) for colorectal procedures. CONCLUSIONS AND
      RELEVANCE: The SSI risk varies by patient and procedure factors as well as
      antibiotic properties but is not significantly associated with prophylactic
      antibiotic timing. While adherence to the timely prophylactic antibiotic measure
      is not bad care, there is little evidence to suggest that it is better care.

PMID- 23552770
TI  - Amplitude-based data selection for optimal retrospective reconstruction in micro
      SPECT.
AB  - Respiratory motion can blur the tomographic reconstruction of positron emission
      tomography or single-photon emission computed tomography (SPECT) images, which
      subsequently impair quantitative measurements, e.g. in the upper abdomen area.
      Respiratory signal phase-based gated reconstruction addresses this problem, but
      deteriorates the signal-to-noise ratio (SNR) and other intensity-based quality
      measures. This paper proposes a 3D reconstruction method dedicated to micro-SPECT
      imaging of mice. From a 4D acquisition, the phase images exhibiting motion are
      identified and the associated list-mode data are discarded, which enables the
      reconstruction of a 3D image without respiratory artefacts. The proposed method
      allows a motion-free reconstruction exhibiting both satisfactory count statistics
      and accuracy of measures. With respect to standard 3D reconstruction (non-gated
      3D reconstruction) without breathing motion correction, an increase of 14.6% of
      the mean standardized uptake value has been observed, while, with respect to a
      gated 4D reconstruction, up to 60% less noise and an increase of up to 124% of
      the SNR have been demonstrated.

PMID- 23552771
TI  - Pure transvaginal excision of mesh erosion involving the bladder.
AB  - INTRODUCTION AND HYPOTHESIS: We present a pure transvaginal approach to the
      removal of eroded mesh involving the bladder secondary to placement of
      transvaginal mesh for management of pelvic organ prolapse (POP) using a mesh kit.
      METHODS: Although technically challenging, we demonstrate the feasibility of a
      purely transvaginal approach, avoiding a potentially more morbid transabdominal
      approach. RESULTS: The video presents the surgical technique of pure transvaginal
      excision of mesh erosion involving the bladder after mesh placement using a
      prolapse kit was performed. CONCLUSIONS: This video shows that purely
      transvaginal removal of mesh erosion involving the bladder can be done safely and
      is feasible.

PMID- 23552772
TI  - An ultra-low Pd loading nanocatalyst with high activity and stability for CO
      oxidative coupling to dimethyl oxalate.
AB  - A Pd/alpha-Al2O3 nanocatalyst with ultra-low Pd loading exhibits high activity
      and stability for CO oxidative coupling to dimethyl oxalate, which was prepared
      by a Cu(2+)-assisted in situ reduction method at room temperature. The small size
      and high dispersion of Pd nanoparticles facilitated by Cu(2+) ions are
      responsible for the excellent catalytic activity.

PMID- 23552773
TI  - [The change of transient receptor potential vanilloid-1 and interleukin-1alpha in
      periodontal tissue during experimental tooth movement].
AB  - PURPOSE: To investigate the expression of TRPV1 and IL-1alpha in Sprague-Dawley
      rats' periodontal ligament (PLD) during experimental tooth movement of different
      orthodontic force and duration, and explore the role of TRPV1 and IL-1alpha in
      orthodontic pain. METHODS: 66 Sprague-Dawley rats were divided into control group
      (n=6), sham operation group (n=6) and experimental group (n=54) randomly.
      Orthodontic force was applied on right first maxillary molar in rats and the
      changes of TRPV1 and IL-1alpha expression were detected by real-time PCR at 4 h,
      8 h, 1 d (three subgroups were added according to different forces: 1 d-30 g, 1 d
      50 g, 1 d-80 g ), 3 d, 5 d, 7 d, 14 d after tooth movement. The data was analyzed
      using SPSS 13.0 software pakage. RESULTS: Following the experimental tooth
      movement, the expression of TRPV1 and IL-1alpha in periodontal tissues were
      significantly up-regulated from 4 h to 7 d, with a peak at 1 d and returned to
      normal level at 1 week. The greater force applied during experimental tooth
      movement at 1 d, the higher expression of TRPV1 and IL-1alpha were detected in
      periodontal tissues. CONCLUSIONS: Experimental tooth movement leads to regular
      change of TRPV1 and IL-1alpha expression in periodontal tissues, which indicates
      that TRPV1 and IL-1alpha may play an important role in orthodontic pain.

PMID- 23552774
TI  - [Effects of rhAm on attachment, proliferation and immigration of human
      fibroblasts].
AB  - PURPOSE: To compare the effects of 25 kDa full-length rhAm and porcine EMPs on
      cell behaviors of human periodontal ligament fibroblasts (HPDLF) and foreskin
      fibroblasts(HFF). METHODS: rhAm was induced by BL21/pET28a-His-SUMO-rhAm express
      system, and 25 kDa full-length rhAm was analyzed by SDS-PAGE and Western blot.
      EMPs were extracted by acetic acid method. HPDLF and HFF were cultured in vitro.
      The cells were treated with rhAm and EMPs at different concentrations. The cell
      adhesion, proliferation and migration assays were qualitatively analyzed. The
      data was statistically analyzed with SAS 5.0 software package. RESULTS: 10-20
      MUg/mL rhAm significantly promoted the adhesion, proliferation and migration of
      HPDLF and HFF (P<0.05), but no significant difference between two proteins was
      found (P>0.05). CONCLUSIONS: 25 kDa rhAm and EMPs shows similar biological
      effects on fibroblast, which indicates that rhAm may play an important role in
      the periodontal regeneration through the activation of fibroblasts.

PMID- 23552775
TI  - [Gene therapy for tongue carcinoma mediated by oral administration of attenuated
      Salmonella harboring tip30 and IFN-gamma genes in nude mouse model].
AB  - PURPOSE: To observe the effect of gene therapy mediated by oral administration of
      attenuated Salmonella carrying tip30 and IFN-gamma genes in human tongue
      carcinoma nude mouse model. METHODS: 25 four-week-old BALB/C male nude mice were
      divided randomly into 5 groups based on the differently harboring genes in the
      recombinant attenuated Salmonella typhimuriums SL7207, which included blank group
      (PBS), control group (SL7207), IFN treatments group (SL7207-pCI-IFN), tip30
      treatment group (SL7207-pCI-tip30) and the combination of IFN and tip30 treatment
      group (SL7207-pCI-tip30/IFN). On 10d after submandibular subcutaneous injection
      of Tca8113 cells into the mice, the recombinant attenuated Salmonella
      typhimuriums were orally administrated 3 times at 1 week interval. The treatment
      effect indicators included the growth curve, the tumor inhabitation rate, the
      survival rate, the apoptosis typical DNA ladder and the protein expressions of
      tip30 and IFN-gamma in tumor cells. Statistical analysis was performed with
      SPSS15.0 software package. RESULTS: The growth curve, the tumor inhabitation rate
      and the survival rate indicated that the tumor in the PBS group constantly grew
      up and induced the animal death in earlier time, while the SL7207 treatment had a
      slight inhibiting effect compared with PBS group. However, the SL7207-pCI-IFN
      group and the SL7207-pCI-tip30 had a moderate inhibiting effect compared with the
      SL7207 group, while the combination of IFN and tip30 had the strongest inhibiting
      effect. The protein expressions of tip30 and IFN-gamma were detected in tumor
      cells while the typical DNA ladders of apoptosis were observed only in the tip30
      gene transfer groups (SL7207-pCI-tip30 and SL7207-pCI-tip30/IFN). CONCLUSIONS:
      The recombinant attenuated Salmonella typhimurium possesses a capacity of gene
      transfer in vivo through oral administration. The combination of the harboring
      tip30 and IFN-gamma genes have synergistic inhibiting tumor effect for tongue
      carcinoma.

PMID- 23552776
TI  - [The isolation and identification of bone marrow mesenchymal stem cells derived
      from rabbit mandible].
AB  - PURPOSE: To investigate the methods of isolation, culture and identification of
      BMMSCs derived from rabbit mandible. METHODS: BMMSCs were collected from rabbit
      mandible and isolated by density gradient centrifugation. Cells were adherently
      cultured in vitro, and P2 or P3 BMMSCs populations were collected and examined.
      Cell growth was observed by inverted microscopy; the propagation of BMMSCs were
      tested by MTT and a growth curve was drawn after statistical analysis; colony
      forming unit-fibroblast(CFU-F) was detected by examination of colony formation;
      the potential of multi-directional differentiation into osteoblasts, adipocytes
      and skeletal muscle cells was estimated by pertinent methods; the surface marks
      of BMMSCs were detected by flow cytometry, the data was analysed using SPSS16.0
      software package. RESULTS: The majority of adherent cells were long fusiform, and
      few were small triangle; the growth curve of BMMSCs showed that every passage
      experienced incubation period, log phase and platform period; the rate of colony
      formation was 37%. Growth of BMMSCs represented the appearance of CFU-F; BMMSCs
      after inducted differentiation showed osteogenic and adipogenic potential. The
      staining of mineralized nodules was positive by alizarin red S and the positive
      staining of oil red O appeared in lipid drops around cell nucleus. The staining
      of skeletal muscle cells was positive by desmin immunofluorescence; the cell
      surface marks assessed with flow cytometry indicated that these BMMSCs expressed
      CD90 and CD146 in high percentage (about 98.7% and 98.1%, respectively).
      CONCLUSIONS: The highly uniformed BMMSCs derived from rabbit mandible can be
      collected. These BMMSCs have the ability of self-replication and propagation, as
      well as potential of multi-directional differentiation in vitro.

PMID- 23552777
TI  - [Construction and identification of a recombinant lentiviral expression plasmid
      pLentiTrident1-hBMP2-Neo-hNGF].
AB  - PURPOSE: To construct and confirm a recombinant lentiviral vector containing
      human bone morphogenetic protein 2 (hBMP2) and human nerve growth factor (hNGF).
      METHODS: The Neomycin gene was digested from pLentiTrident1-EGFP-Neo and then was
      subcloned into lentiviral vector. The hBMP2 and hNGF genes were amplified by
      polymerase chain reaction (PCR), and then the PCR product was inserted to proper
      sites of the vector. Finally, the recombinant vector pLentiTrident1-hBMP2-Neo
      hNGF was confirmed by agarose gel electrophoresis and DNA sequence analysis.
      RESULTS: The construction of recombinant lentiviral vector pLentiTrident-hBMP2 
      Neo-hNGF was confirmed through restriction enzyme maping analysis and DNA
      sequencing. CONCLUSIONS: The recombinant lentiviral vector which can coexpress
      hBMP2 and hNGF is successfully constructed,which lays a solid foundation of
      studying the effect of neuro factors on bone regeneration.

PMID- 23552778
TI  - [Effect of three dental alloys on cytotoxicity and apoptosis related gene
      expression in L929 cells].
AB  - PURPOSE: To investigate the effect of the liching liquids of 3 different kinds of
      dental alloys on L929 cells both at cell level and molecular level. METHODS: The
      fibroblast L929 cells of mouse were treated in vitro with leaching liquids of 3
      different kinds of dental alloys which were Au alloy, Ti and Ni-Cr alloy,
      respectively. The RPMI 1640 cell medium containing 10% fetal calf serum was
      served as a negative control and the Cu alloy was served as a positive control.
      The cytotoxicities of 3 dental alloys were evaluated by means of MTT and the
      effects of these alloys on the expression of caspase-3, caspase-8 and caspase-9
      of L929 cells were examined by RT-PCR method and immunohistochemistry. The data
      was analyzed with SPSS13.0 software package. RESULTS: The cytotoxicity of three
      groups were all in grade 0 after 48 hours of cultures. Caspase-8 had no change in
      all groups at mRNA level.The expression of caspase-3 and caspase-9 in Ni-Gr alloy
      group was significantly different from other groups. CONCLUSIONS: It is suggested
      from the results that the leaching liquids of Ni-Cr alloy may induce cell
      apoptosis through mitochondrion pathway.

PMID- 23552779
TI  - [Construction and validation of a three-dimensional finite element model of
      cranio-maxillary complex with sutures in unilateral cleft lip and palate
      patient].
AB  - PURPOSE: To explore an effective method to construct and validate a finite
      element model of the unilateral cleft lip and palate(UCLP) craniomaxillary
      complex with sutures, which could be applied in further three-dimensional finite
      element analysis (FEA). METHODS: One male patient aged 9 with left complete lip
      and palate cleft was selected and CT scan was taken at 0.75mm intervals on the
      skull. The CT data was saved in Dicom format, which was, afterwards, imported
      into Software Mimics 10.0 to generate a three-dimensional anatomic model. Then
      Software Geomagic Studio 12.0 was used to match, smoothen and transfer the
      anatomic model into a CAD model with NURBS patches. Then, 12 circum-maxillary
      sutures were integrated into the CAD model by Solidworks (2011 version). Finally
      meshing by E-feature Biomedical Modeler was done and a three-dimensional finite
      element model with sutures was obtained. A maxillary protraction force (500 g per
      side, 20 degrees  downward and forward from the occlusal plane) was applied.
      Displacement and stress distribution of some important craniofacial structures
      were measured and compared with the results of related researches in the
      literature. RESULTS: A three-dimensional finite element model of UCLP
      craniomaxillary complex with 12 sutures was established from the CT scan data.
      This simulation model consisted of 206 753 individual elements with 260 662
      nodes, which was a more precise simulation and a better representation of human
      craniomaxillary complex than the formerly available FEA models. By comparison,
      this model was proved to be valid. CONCLUSIONS: It is an effective way to
      establish the three-dimensional finite element model of UCLP cranio-maxillary
      complex with sutures from CT images with the help of the following softwares:
      Mimics 10.0, Geomagic Studio 12.0, Solidworks and E-feature Biomedical Modeler.

PMID- 23552780
TI  - [A cone-beam computed tomography study of changes in canal isthmus of maxillary
      first premolars before and after instrumentation].
AB  - PURPOSE: To analyze the difference of the incidence and type of root canal
      isthmus in maxillary first premolars with single root and two canals before and
      after instrumentation using cone-beam computed tomography(CBCT), and investigate
      the application and effect of CBCT in analysis of root canal isthmus. METHODS:
      Sixty-six extracted maxillary first premolar with single root and two canals were
      scanned by CBCT before and after instrumentation. The incidence and type of
      isthmus before and after instrumentation were recorded and compared. The data was
      subjected to X(2) test and rank sum test with SPSS13.0 software package. RESULTS:
      The incidence of isthmus was different at each 1 mm level within apical 0-6 mm in
      maxillary first premolar with single root and two canals before and after
      instrumentation (P<0.05), which was lowest at apical 1 mm and highest at apical 6
      mm; the proportion of partial isthmus (PI) was significantly higher than complete
      isthmus (CI) (P<0.05). After instrumentation, the incidence of isthmus in apical
      0-6 mm decreased (P<0.05), but the proportion of CI increased. CONCLUSIONS: The
      difference of root canal isthmus structure before and after instrumentation can
      be defined accurately with CBCT. CBCT is an ideal method to evaluate root canal
      isthmus.

PMID- 23552781
TI  - [Establishment and experimental study of alveolar preservation before dental
      implantation in Beagle dogs].
AB  - PURPOSE: To establish the model of alveolar ridge preservation after tooth
      extraction for dental implant replacement, and to observe the effect of tissue
      engineered bone on osseointegration. METHODS: Isolated BMSCs were expanded and
      osteogenically induced in vitro. The tissue engineering complex was constructed
      with BMSCs/A-PCPC in vitro. Six extraction sockets, with three on each side, were
      created in the mandibles of four Beagle dogs by extracting the second, third and
      fourth premolars. BMSCs/A-PCPC were placed on one side of the extraction sockets,
      while autogenous bone, A-PCPC and nothing were placed on the other side as
      control. X-ray and CT scans were conducted 1day, 4 and 12 weeks after operation
      to detect the change of the alveolar ridge. The bone of sockets were harvested at
      8-week post-implantation and subject to histological for evaluating. SPSS17.0
      software package was used for data analysis. RESULTS: Radiographs demonstrated
      higher radiodensity in group of complex than in simple materials group,
      autogenous bone group after 4 weeks. Hard tissue biopsy at 12-week showed that
      bone activity of BMSCs/A-PCPC complex was better than the other groups. Spiral CT
      analysis showed that alveolar ridge of each group experienced a certain degree of
      absorption. At 12-week, the alveolar ridge height reduction values in A-PCPC
      group was smaller than in A-PCPC group, autogenous bone group and blank group
      (P<0.05). CONCLUSION: The BMSCs/A-PCPC complex is favorable for preservation of
      alveolar ridge.

PMID- 23552782
TI  - [An anatomical study of maxillary sinus septum of Han population in Jiangsu
      region using cone-beam CT].
AB  - PURPOSE: To examine the anatomical variation of maxillary sinus septum of Han
      nationality in Jiangsu region by using cone-beam computed tomography (CBCT)
      combined with Simplant software in order to provide anatomical basis and
      operation instruction for oral implants after maxillary sinus lifting. METHODS:
      CBCT image data were collected from 424 patients for analysis of maxillary sinus
      septa. Digital imaging and communications in medicine (Dicom) image files were
      fed into the computer-aided Simplant software and used to analyze the prevalence,
      location, height, orientation, and morphology of maxillary sinus septa through
      three-dimensional reconstruction. The data was analyzed with SPSS17.0 software
      package. RESULTS: The proportion of the occurrence of maxillary sinus septa in
      424 subjects was 44.81% and 21.23% of the subjects (n=90) had multiple sinus
      septa, while 20.52% had bilateral sinus septa (n=87). Totally 848 maxillary
      sinuses were observed in this study and 277 sinuses had septa with a proportion
      of 32.67%. The prevalence of septa was not significantly related to gender, age,
      and the presence or absence of teeth. Septa were located most frequently in the
      middle of maxillary sinus (59.94%). The mean height of sinus septa was (5.90+/
      3.65) mm and (5.54+/-2.87) mm in the right and left maxillary sinus,
      respectively. The mean length of sinus septa was (8.15+/-2.40) mm and (7.88+/
      2.73) mm in the right and left maxillary sinus, respectively. CONCLUSIONS: Nearly
      44.81% of Han population in Jiangsu region have maxillary sinus septa. The CBCT
      imaging technique can provide comprehensive and accurate quantitative analysis of
      maxillary sinus septa and is meaningful to provide anatomical basis and clinical
      guidance before sinus augmentation procedures.

PMID- 23552783
TI  - [Atrophic glossitis is attributed to cobalamin deficiency].
AB  - PURPOSE: To analyze the causes of atrophic glossitis(AG) and to explore the
      relationship between AG and serum cobalamin, folate levels. METHODS: A total of
      213 patients with AG treated from Jan.1979 to Jun. 2010 were analyzed for the
      causes of AG. Serum cobalamin, folate levels and complete blood count were tested
      in newly enrolled AG patients from Sep. 2010 to Aug. 2011. All data were analyzed
      with SPSS 16.0 software package for Student's t test. RESULTS: There were 97 AG
      patients (45.4%) suffering from megaloblastic anemia (MA)/ macrocytosis. Among
      the 72 newly enrolled AG patients, fifty had cobalamin deficiency. Meanwhile,
      serum folate levels were increased in cobalamin deficiency group. CONCLUSIONS:
      Cobalamin deficiency is the common cause both of MA/macrocytosis and AG, also may
      be the main cause of AG. Furthermore, AG may be the early clinical manifestation
      of cobalamin deficiency.

PMID- 23552784
TI  - [Expression and clinical significance of ErbB3 binding protein ebp1, E-cadherin,
      ICAM-1 and matrix metalloproteinase-9 in salivary adenoid cystic carcinoma].
AB  - PURPOSE: To investigate the expression of ErbB3 binding protein ebp1, E-cadherin,
      ICAM-1 and matrix metalloproteinase-9(MMP-9) in salivary adenoid cystic
      carcinoma(SACC), and to explore their relationship with clinical pathological
      features. METHODS: Two-step immunohistochemical staining method was used to
      detect the expression of ebp1 E-cadherin, ICAM-1 and MMP-9 in 33 cases with human
      SACC and 33 with para-cancerous normal tissues. All data were analyzed with
      SPSS17.0 software package. RESULTS: Positive expression rate of ebp1 in SACC was
      84.85%, lower than in normal salivary tissues(96.97%). Ebp1 expression was
      significantly correlated to pathological pattern and clinical stage(P<0.05), but
      not correlated to gender and age. Positive expression rate of ebp1 at I-II stage
      was higher than that of SACC at III-IV stage; in regard to pathological typing,
      higher expression was found in adenoid tubular type than in solid type; the
      positive expression rate in patients with tumor metastasis was lower than in
      patients without metastasis (P<0.05). Expression of ebp1 had a positive
      relationship with E-cadherin (r=0.851,P<0.01), while a negative relationship was
      found with MMP-9 (r=-0.364,P<0.05). CONCLUSIONS: Expression of ebp1 may be
      associated with progression of SACC. Ebp1 has important role in the generation
      and evolution of adenoid cystic carcinoma, and can be used as a useful indicator
      for clinical assessment of tumor biological behavior and prognosis in patients
      with adenoid cystic carcinoma.

PMID- 23552785
TI  - [Detection of anaerobes and drug sensitivity from the periodontal pockets of
      patients with combined periodontal-endodontic lesions].
AB  - PURPOSE: To investigate the correlation between the composition of bacterial
      flora isolated from deep periodontal pockets with combined periodontal-endodontic
      lesions, and to test the antibiotic susceptibility of anaerobes. METHODS:
      Microbial samples were taken from 82 deep periodontal pockets with combined
      periodontal-endodontic lesions using adequate techniques, and divided into two
      groups: endo-perio group and perio-endo group. Antibiotic susceptibility of
      cultivable anaerobes were tested with agar dilution method. RESULTS: Eighty-six
      cultivable anaerobes were isolated, including Streptococcus spp, Prevotella spp,
      Actinomycetes spp, Veillonella spp, Fusobacterium spp and etc. 53.4% were gram
      positive anaerobes, while 46.51% were gram-negative anaerobes. The detection rate
      of anaerobes in endo-perio group and that in perio-endo group had significant
      difference. Most isolated anaerobes were sensitive to six drugs. The resistance
      rates of penicillin, clindamycin, metronidazole were 6.8%, 13.9% and 2.2%.
      CONCLUSIONS: There is a close relationship between anaerobes and combined
      periodontal-endodontic lesions. Drug sensitive susceptibility should be detected
      prior to clinical treatment of combined periodontal-endodontic lesions.

PMID- 23552786
TI  - [Evaluation of effects of quality scale for removable partial dentures in
      clinical application].
AB  - PURPOSE: To evaluate the effects of quality scale for removable partial dentures
      (RPD)in clinical application. METHODS: Quality scale for removable partial
      dentures was designed. Twelve items were devised for visual survey and try-in in
      base, artificial teeth, clasp, rest, connector and adjustment. The assessments
      were divided into 3 grades A, B and C. Four commercial dental laboratories were
      divided into experimental group and control group randomly. All RPD made in two
      groups were given score with the quality scale by single-blind method. In the
      experimental group,the technicians were familiar with the quality scale. The
      assessments were periodically feedbacked to administrative staffs and exchanges
      were carried out between doctors and technicians by telephone. No feedback
      information was provided in the control group. The assessments were compared
      between the two groups. The data was analyzed with SPSS17.0 software package.
      RESULTS: The scores of assessments for base, artificial teeth, clasp, rest,
      connector and adjustment in the experimental group were greater than that in the
      control group. The difference was significant between the two groups by analysis
      of variance (P<0.01). The grade A and C for RPD used acrylic resin, flexible
      resin and cast framework in the experimental group was 27.2%,39.5%,40.6% and
      9.2%, 7.9%,7.2%, respectively. The grade B was in the majority. In the control
      group, the grade A and C was 9.4%,15.6%,15% and 40.6%,23.6%,25%,respectively. The
      majority was grade B and the grade C was significantly higher than the
      experimental group(P<0.05). CONCLUSION: Applying the quality scale of RPD can
      improve the fabricating quality of prosthesis.

PMID- 23552787
TI  - [Evaluation of the fiber-reinforced composite periodontal splint on fixing loose
      teeth with severe periodontitis].
AB  - PURPOSE: To evaluate the clinical effects of fiber-reinforced composites for
      splinting loose teeth after periodontal treatment. METHODS: Patients with severe
      periodontitis (104 teeth) were randomly divided into fiber-reinforced composites
      group (58 teeth) and wire-ligation fixation group (46 teeth). After periodontal
      treatment, the loose teeth were fixed by fibre reinforced composites and wire
      ligation. After 1 year of clinical observation,probing depth(PD), attachment
      loss(AL), gingival sulcus bleeding index (SBI)and plaque index(PLI)were measured.
      The data was analyzed with SPSS13.0 software package. RESULTS: Six months after
      fixation, PD and AL became shallower (P<0.05), however, no significant difference
      was observed in SBI and PLI in the experimental group. In the control group, PD
      and AL became shallower, SBI and PLI values were higher (P<0.05). SBI and PLI in
      wire-ligation fixation group were higher than that in fibre reinforced composites
      group six months after fixation (P<0.05). CONCLUSIONS: High-strength fibers in
      the periodontal splint is effective for loose tooth fixation in patient with
      severe periodontitis.

PMID- 23552788
TI  - [Clinical study on the effects of single visit root canal treatment of chronic
      periapical periodontitis by two kinds of root canal preparation instruments
      system].
AB  - PURPOSE: To investigate the different incidence of postoperative pain and long
      term follow-up curative effects in patients with chronic periapical periodontitis
      undergoing single visit root canal treatment by two kinds of canal preparation
      instruments system. METHODS: Ninety-eight permanent teeth with chronic periapical
      periodontitis were divided into two groups randomly. One group was prepared with
      nickel-titanium instruments, the other group was prepared with K files. After
      canal preparation, all the teeth underwent canal filling immediately. The
      different incidence of postoperative pain and long-term follow-up curative
      effects were recorded. Statistical analysis was carried out using SPSS13.0
      software package. RESULTS: One week after treatment, the rate of serious symptom
      of periapical periodontitis in the Ni-Ti group was less than that in the K file
      group (P<0.05 ). 18 months after treatment, the curative effect of two groups had
      no significant difference (P>0.05 ). CONCLUSIONS: Nickel-titanium instrument used
      in treatment of chronic periapical periodontitis lead to less serious
      postoperative reaction than K file instruments, but the same long-term follow-up
      curative effects as K file instruments. Nickel-titanium instruments system is
      worthy of wide application in patients with chronic periapical periodontitis
      undergoing single visit root canal treatment.

PMID- 23552789
TI  - [Influence of smoking on survival rate of endosseous implant: a meta analysis].
AB  - PURPOSE: To evaluate the influence of smoking on survival rate of endosseous
      implant. METHODS: The literatures published before the year 2012 involving
      influence of smoking on survival rate of endosseous implant were searched in
      PubMed,Embase and Cochrane databases. Data from the literatures conforming to the
      inclusion criteria and exclusive criteria were selected and a meta-analysis was
      carried out. RESULTS: Sixteen literatures conforming to the inclusion criteria
      and exclusive criteria were screened out, which were prospective or retrospective
      cohort studies. Meta analysis using random effects model showed smoking patients
      had higher risk to lose endosseous implants than non-smoking patients
      (synthesized OR 2.24,95% CI 1.66-3.01,P<0.01), which implied the survival rate of
      endosseous implant in smoking patients was lower than in non-smoking patients.
      Heterogeneity source was not figured out by meta regression and subgroup
      analysis. When sensitivity analysis was done by using fixed and random effects
      model alternatively or excluding articles in which the distribution of implant
      surface characteristics were uneven between smoking and non-smoking group, result
      was not changed obviously. CONCLUSIONS: The existing limited evidences show that
      smoking is harmful to the survival of endosseous implants. This meta-analysis is
      restricted by the literatures' quality and quantity and the results need to be
      confirmed by high quality studies.

PMID- 23552790
TI  - [Practice and experience in early clinical education of dental students in
      preventive dentistry].
AB  - To help dental students acquaint the medical environment, doctor-patient
      communication and relationship, early clinic education was arranged in our
      college of stomatology. The interesting topics were chosen to enhance the
      learning enthusiasm of the students in the teaching practice of preventive
      dentistry. Students were encouraged to practice the skill of doctor-patient
      communication. To obtain the satisfactory teaching effect and aim, it was
      important to pay attention to the aspects in the groups and clinical practice.
      Early clinic education in preventive dentistry help the students understand the
      specialty of preventive dentistry.

PMID- 23552791
TI  - [Clinical retrospective analysis of 19 cases of intraparotid facial nerve
      schwannoma].
AB  - PURPOSE: With literatures review, this retrospective study was aimed to analyze
      the clinic characteristics and treatment of intraparotid facial nerve schwannoma
      (IFNS) treated in our department. METHODS: All cases treated in the Department of
      Oral and Maxillofacial Surgery and diagnosed as IFNS pathologically, from 2000
      2007, were reviewed. The data of clinical symptoms, preoperative radio graphic
      imagings, preoperative diagnosis, tumor size and treatment method were collected
      and analyzed. RESULTS: Totally, 19 cases of IFNS were collected and reviewed. 3
      of 19 (15.8%) were diagnosed as IFNS preoperatively, 2 cases were diagnosed by
      fine needle aspiration pathology, and 1 by physical examination. IFNS could
      occurred in any part of the facial nerve, 8 of 19 cases (43.1%) originated from
      the trunk of facial nerve in our cases. Nerve-sparing was applied in 12 cases,
      and the facial nerve was sectioned and anastomosed in 2 of these 12 cases; tumor
      resection with involved facial nerve were applied in 6 cases, and 5 of these 6
      cases with facial nerve defect after tumor removal were repaired by auricular
      nerve transplantation, 1 case with nerve defect was not repaired; partial
      resection of the tumor was applied in 1 of the 19 cases. There was no tumor
      relapse in all 19 cases after 15-79 months of follow-up, while the function of
      the tumor-involved facial nerve were disturbed in all cases. CONCLUSIONS:
      Preoperative diagnosis of IFNS is difficult, and the diagnosis is based on
      preoperative fine needle aspiration or post operative pathology. Both nerve
      sparing and nerve-resection approach can rarely keep the facial nerve function
      well after tumor removal.

PMID- 23552792
TI  - [Salivary duct carcinoma: report of 6 cases and review of the literature].
AB  - PURPOSE: To summarize the clinicopathologic characteristics, treatment and
      prognosis of salivary duct carcinoma. METHODS: Six cases of salivary duct
      carcinoma treated in our hospital were reported. And the literatures were
      reviewed. All cases were proved by operation and pathology. The clinical
      characteristics, histological features, therapeutic method and prognosis were
      analyzed. RESULTS: Salivary duct carcinoma predominantly influenced old male
      patients and mainly occurred in the parotid gland. Physical examination revealed
      a firm, immobile and poorly defined mass accompanied by nerve infiltrated
      symptom. The histological appearance was characterized by solid cell nests with
      ductal structures and central comedonecrosis. Treatment required extensive
      resection and radical neck dissection with postoperative radiotherapy. The
      clinical course was marked by development of both local disease recurrence as
      well as cervical lymph node and distant metastasis. CONCLUSIONS: Salivary duct
      carcinoma is a rare malignant salivary tumour with poor prognosis. Extensive
      resection is the key to improve the survival rate.

PMID- 23552793
TI  - [Use of "gelatamp" colloidal silver gelatin sponge to prevent dry socket after
      extracting mandibular impacted teeth].
AB  - PURPOSE: To study the clinical effect of "gelatamp" colloidal silver gelatin
      sponge on preventing dry socket after extracting the mandibular impacted teeth.
      METHODS: 1350 teeth extracted from 976 patients who needed to extract the
      mandibular impacted teeth were divided into group A, group B and group C
      randomly. "Gelatamp" colloidal silver gelatin sponge was implanted into alveolar
      socket after teeth extraction in group A, with absorbable gelatin sponge was
      implanted into alveolar socket in group B and nothing was implanted into alveolar
      socket in group C. The incidence of dry socket was observed, the data was
      analyzed using SPSS10.0 software package. RESULTS: The incidence of dry socket
      was 0.44% in group A, 2% in group B and 4.44% in group C. There was significant
      difference in the incidence of dry socket between group A and group C(P<0.01).
      There was also significant difference between group B and group C(P<0.05) and
      between group A and group B(P<0.05). CONCLUSIONS: The results demonstrate that
      "gelatamp" colloidal silver gelatin sponge can prevent the occurrence of dry
      socket after teeth extraction, which is of wide clinical use.

PMID- 23552794
TI  - [Osteotome sinus floor elevation technique without grafting material: clinical
      analysis of eight cases].
AB  - PURPOSE: To study the clinical results of XIVE implants placed immediately after
      sinus floor elevation using osteotomes without bone grafting. METHODS: Totally 14
      XIVE implants were placed in 8 patients immediately after sinus floor elevation
      using osteotomes without bone grafting. The survival rates of the implants during
      the prosthodontic process and six months after the crowns fabricated were
      recorded and analyzed. RESULTS: One implant was loosen and extracted during the
      prosthodontic process and no implant failed six months after the crowns were
      placed. The survival rate of the implants in this study was 92.9%. CONCLUSIONS:
      Implants placed immediately after sinus floor elevation using osteotomes without
      bone grafting could achieve higher survival rates, which is similar to the
      reported survival rates in dental implants with bone grafting.

PMID- 23552795
TI  - [Polymorphous low-grade adenocarcinoma of the palate with cervical lymph node and
      distant metastasis: report of one case and review of the literature].
AB  - Polymorphous low-grade adenocarcinoma is a rare salivary gland tumor with lower
      rate of local and regional metastasis and rare distant metastasis. The prognosis
      is relatively good. This paper reported a case of palatal polymorphous low-grade
      adenocarcinoma with cervical lymph node and distant metastasis, and discussed
      clinical characteristics, differential diagnosis, treatment, prognosis based on
      literature review.

PMID- 23552796
TI  - [Cat scratch disease with deradenoncus and high fever: report of one case].
AB  - Cat scratch disease (CSD) is a bacterial disease caused by Bartonella henselae.
      It is mainly characterized by self-limiting lymphadenopathy in the draining site
      after cat scratch or bite. This paper reported a case of cat scratch disease with
      deradenoncus and high fever, and discussed the etiology, pathogenesis,
      epidemiology, pathology, clinical characteristics, diagnosis and treatment
      methods of CSD.

PMID- 23552797
TI  - [The role of occlusal factors in the occurrence of vertical root fracture].
AB  - PURPOSE: To investigate the occlusal characteristics and the condition of tooth
      abrasion in patients with vertical root fracture and to discuss the etiology of
      the vertical root fracture and the relationships between occlusal disorder, tooth
      abrasion and vertical root fracture of molars. METHODS: Two hundred and seventy
      seven cases of root fracture patients were included in the study, with 309
      involved teeth. The periodontal status, occlusal wear, occlusal contact area,
      occlusal interference, occlusal trauma and the X-ray film were observed and
      evaluated. All statistical analyses were performed using SPSS13.0 software
      package. Date was expressed as n(%).Differences between groups were compared
      using X(2) test with SPSS 13.0 software package. RESULTS: Vertical root fracture
      occurred in patients aging 40 to 60 years, the first molar mesial root or buccal
      root was mostly involved. Periodontal tissue destruction was significantly
      greater than roots without vertical fracture, with formation of localized
      periodontal pocket. Severe occlusal surface wear, high and steep non-work tip,
      working tip abrasion, deep occlusal surface concave and lower distal edge were
      seen in the affected teeth.The degree of vertical root fracture was related to
      the site of deep occlusal surface concave. Occlusal interference or occlusal
      trauma was the predisposing factors of vertical root fracture. CONCLUSIONS:
      Vertical root fracture is associated with malocclusion and tooth abrasion.
      Changes of occlusion leads to over occlusal force and abnormal direction of
      occlusal force, which may be important factor of vertical root fracture.

PMID- 23552799
TI  - In vivo imaging demonstrates ATP release from murine keratinocytes and its
      involvement in cutaneous inflammation after tape stripping.
AB  - Adenosine 5'-triphosphate (ATP) release from keratinocytes has been observed in
      various stress models in vitro, but studies demonstrating epidermal ATP release
      in vivo are limited. To visualize extracellular ATP (eATP) in vivo, we developed
      enhanced green-emitting luciferase immobilized on agarose beads (Eluc-agarose).
      Subcutaneous injection of Eluc-agarose together with ATP into the dorsal skin of
      BALB/c mice following intraperitoneal luciferin injection produced detectable and
      measurable bioluminescence using an in vivo imaging system. Using Eluc-agarose,
      we demonstrated in vivo that bright bioluminescence was observed from 1 to 20
      minutes after repeated tape stripping of murine skin. This bioluminescence was
      suppressed by the local administration of apyrase. Eluc-agarose bioluminescence
      was observed only in tape-stripped skin with transepidermal water loss (TEWL)
      between 100 and 140 g m(2) h(-1), indicating a loss of bioluminescence with
      excessive tape stripping (TEWL>140 g m(-2) h(-1)). Histologically, tape-stripped
      skin with detectable eATP had a viable epidermis and a subepidermal neutrophil
      infiltrate, and administration of apyrase reduced the inflammatory infiltrate.
      Neither a viable epidermis nor an upper dermal neutrophil infiltrate was observed
      after excessive tape stripping. These results suggest that tape stripping prompts
      ATP release from viable keratinocytes, which facilitates inflammatory cell
      migration. Eluc-agarose may be useful in the in vivo detection of eATP in murine
      models of skin diseases. 

PMID- 23552798
TI  - Local arginase 1 activity is required for cutaneous wound healing.
AB  - Chronic nonhealing wounds in the elderly population are associated with a
      prolonged and excessive inflammatory response, which is widely hypothesized to
      impede healing. Previous studies have linked alterations in local L-arginine
      metabolism, principally mediated by the enzymes arginase (Arg) and inducible
      nitric oxide synthase (iNOS), to pathological wound healing. Over subsequent
      years, interest in Arg/iNOS has focused on the classical versus alternatively
      activated (M1/M2) macrophage paradigm. Although the role of iNOS during healing
      has been studied, Arg contribution to healing remains unclear. Here, we report
      that Arg is dynamically regulated during acute wound healing. Pharmacological
      inhibition of local Arg activity directly perturbed healing, as did Tie2-cre
      mediated deletion of Arg1, revealing the importance of Arg1 during healing.
      Inhibition or depletion of Arg did not alter alternatively activated macrophage
      numbers but instead was associated with increased inflammation, including
      increased influx of iNOS(+) cells and defects in matrix deposition. Finally, we
      reveal that in preclinical murine models reduced Arg expression directly
      correlates with delayed healing, and as such may represent an important future
      therapeutic target. 

PMID- 23552800
TI  - Optimization of transient gene expression system in Gerbera jemosonii petals.
AB  - Low transformation efficiency and long generation time for production of
      transgenic Gerbera jemosonii plants leads to vulnerable gene function studies.
      Thus, transient expression of genes would be an efficient alternative. In this
      investigation, a transient expression system for gerbera petals based on the
      Agrobacterium infiltration protocol was developed using the reporter genes beta
      glucuronidase (gus) and green florescence protein (gfp). Results revealed the
      incapability of using the gfp gene as a reporter gene for transient expression
      study in gerbera flowers due to the detection of green fluorescent color in the
      non-infiltrated gerbera flower petals. However, the gus reporter gene was
      successfully utilized for optimizing and obtaining the suitable agroinfiltration
      system in gerbera flowers. The expression of GUS was detectable after three days
      of agroinfiltration in gerbera cultivars "Express" and "White Grizzly" with dark
      pink and white flower colors, respectively. The vacuum agroinfiltration protocol
      has been applied on the cultivar "Express" for evaluating the transient
      expression of the two genes involved in the anthocyanin pathway (iris-dfr and
      petunia-f3' 5'h), which is responsible for the color in flowers. In comparison to
      the control, transient expression results showed change in the anthocyanin
      pigment in all infiltrated flowers with color genes. Additionally, blue color was
      detected in the stigma and pollen grains in the infiltrated flowers. Moreover,
      blue colors with variant intensities were observed in produced calli during the
      routine work of stable transformation with f3' 5'h gene.

PMID- 23552801
TI  - Effects of hydrogen dissociation on the infrared emission spectra of naphthalene:
      theoretical modeling.
AB  - The IR emission spectroscopy of naphthalene and its singly- and doubly
      dehydrogenated radicals has been modeled using kinetic Monte Carlo simulations,
      taking into account the various relaxation pathways of radiative emission and
      hydrogen loss. Our modeling relies on quantum chemistry ingredients that were
      obtained from dedicated calculations based on density functional theory,
      including explicitly anharmonicity contributions. Our results show that the
      fragmentation products significantly contribute to the overall IR emission
      spectrum, especially to the intensity ratios between bands. Owing to the likely
      presence of polycyclic aromatic hydrocarbons in the interstellar medium, these
      findings are particularly relevant in the astrophysical context.

PMID- 23552802
TI  - Three-month stability of the CogState brief battery in healthy older adults, mild
      cognitive impairment, and Alzheimer's disease: results from the Australian
      Imaging, Biomarkers, and Lifestyle-rate of change substudy (AIBL-ROCS).
AB  - Large prospective studies of Alzheimer's disease (AD) have sought to understand
      the pathological evolution of AD and factors that may influence the rate of
      disease progression. Estimates of rates of cognitive change are available for 12
      or 24 months, but not for shorter time frames (e.g., 3 or 6 months). Most
      clinical drug trials seeking to reduce or modify AD symptoms have been conducted
      over 12- or 24-week periods. As such, we aimed to characterize the performance of
      a group of healthy older adults, adults with amnestic mild cognitive impairment
      (aMCI), and adults with AD on the CogState battery of tests over short test
      retest intervals. This study recruited 105 healthy older adults, 48 adults with
      aMCI, and 42 adults with AD from the Australian Imaging, Biomarkers, and
      Lifestyle study and administered the CogState battery monthly over 3 months. The
      CogState battery of tests showed high test-retest reliability and stability in
      all clinical groups when participants were assessed over 3 months. When
      considered at baseline, the CogState battery of tests was able to detect AD
      related cognitive impairment. The data provide important estimates of the
      reliability, stability, and variability of each cognitive test in healthy older
      adults, adults with aMCI, and adults with AD. This may potentially be used to
      inform future estimates of cognitive change in clinical trials.

PMID- 23552803
TI  - The use of humor in patients with recurrent ovarian cancer: a phenomenological
      study.
AB  - OBJECTIVE: Humor has been shown to decrease the use of pain medicine, improve
      mood, and decrease stress. However, the timing and setting for using humor can be
      perceived differently depending on the patient and the context. Our objective was
      to better understand how patients with recurrent ovarian cancer experience humor
      to gain insight into the feasibility of using humor as a therapeutic adjunct.
      METHODS: We conducted structured patient interviews with women being treated for
      recurrent ovarian cancer. The phenomenological method of Colaizzi was used to
      gain an in-depth understanding of how women with recurrent ovarian cancer use and
      view humor in relation to their diagnosis. RESULTS: Most patients used humor to
      cope with cancer and felt that humor alleviated their anxiety. The use of humor
      by physicians and nurses was perceived as appropriate and positive. A previous
      relationship with a physician was often felt necessary before the use of humor.
      Humor was often perceived not only in traditional jokes but was also found in
      humorous anecdotes from the caregiver's life outside of medicine. CONCLUSIONS:
      This study revealed that humor is an often used coping mechanism for women with
      recurrent ovarian cancer and subjectively helps alleviate anxiety. The use of
      humor by physicians was found to be universally perceived as appropriate and
      positive. The waiting area seems to be a place where humorous experiences would
      be welcomed. These findings provide additional insight into the role that humor
      plays in the lives of patients with recurrent ovarian cancer.

PMID- 23552805
TI  - First-line paclitaxel and carboplatin in persistent/recurrent or advanced
      cervical cancer: a retrospective analysis of patients treated at Brazilian
      National Cancer Institute.
AB  - OBJECTIVE: Cervical cancer represents the third most commonly diagnosed cancer
      and the fourth cause of cancer death in women worldwide. In the palliative
      scenario, the combination of paclitaxel and cisplatin is widely used. Carboplatin
      is also an active agent in cervical cancer, and its association with paclitaxel
      could represent a well-tolerated, less toxic, and effective therapeutic option.
      The objective of this study was to evaluate response rate, progression-free
      survival, overall survival, and toxicity of carboplatin and paclitaxel in first
      palliative line for cervical cancer. METHODS: A retrospective search of database
      at Brazilian National Cancer Institute was performed, and all patients with
      persistent/recurrent and advanced cervical cancer treated with paclitaxel and
      carboplatin in first palliative line, between August 2008 and January 2010, were
      included. RESULTS: A total of 153 women were enrolled. Objective responses were
      documented in 34.6% (5.2% of complete responses and 29.4% of partial responses).
      With a median follow-up of 27.8 months, the median progression-free survival was
      5.2 months, and the median overall survival was 10.63 months. The most common
      toxicity was myelosuppression: grades 3 and 4 anemia, neutropenia, and
      thrombocytopenia observed in 43.0%, 17.8%, and 9.2% of the cases, respectively.
      Neurotoxicity was presented by 30.7% of the patients. Renal toxicity was detected
      in 21.9% of the patients, but only 4.0% were grade 3, and none were grade 4.
      CONCLUSIONS: This retrospective study has demonstrated that paclitaxel
      carboplatin is an active and well-tolerated regimen for the treatment of advanced
      cervical cancer.

PMID- 23552804
TI  - Ribonucleotide reductase expression in cervical cancer: a radiation therapy
      oncology group translational science analysis.
AB  - OBJECTIVE: To evaluate pretherapy ribonucleotide reductase (RNR) expression and
      its effect on radiochemotherapeutic outcome in women with cervical cancer.
      METHODS/MATERIALS: Pretherapy RNR M1, M2, and M2b immunohistochemistry was done
      on cervical cancer specimens retrieved from women treated on Radiation Therapy
      Oncology Group (RTOG) 0116 and 0128 clinical trials. Enrollees of RTOG 0116 (node
      positive stages IA-IVA) received weekly cisplatin (40 mg/m(2)) with amifostine
      (500 mg) and extended-field radiation then brachytherapy (85 Gy). Enrollees of
      RTOG 0128 (node-positive or bulky >=5 cm, stages IB-IIA or stages IIB-IVA)
      received cisplatin (75 mg/m(2)) on days 1, 23, and 43 and 5-FU (1 g/m(2) for 4
      days) during pelvic radiation then brachytherapy (85 Gy), plus celecoxib (400 mg
      twice daily, day 1 through 1 year). Disease-free survival (DFS) was estimated
      univariately by the Kaplan-Meier method. Cox proportional hazards models
      evaluated the impact of RNR immunoreactivity on DFS. RESULTS: Fifty-one tissue
      samples were analyzed: 13 from RTOG 0116 and 38 from RTOG 0128. M1, M2, and M2b
      overexpression (3+) frequencies were 2%, 80%, and 47%, respectively. Low-level (0
      1+, n = 44/51) expression of the regulatory subunit M1 did not associate with DFS
      (P = 0.38). High (3+) M2 expression occurred in most (n = 41/51) but without
      impact alone on DFS (hazard ratio, 0.54; 95% confidence interval, 0.2-1.4; P =
      0.20). After adjusting for M2b status, pelvic node-positive women had increased
      hazard for relapse or death (hazard ratio, 5.5; 95% confidence interval, 2.2
      13.8; P = 0.0003). CONCLUSIONS: These results suggest that RNR subunit expression
      may discriminate cervical cancer phenotype and radiochemotherapy outcome. Future
      RNR biomarker studies are warranted.

PMID- 23552806
TI  - Women 50 years or younger with endometrial cancer: the argument for universal
      mismatch repair screening and potential for targeted therapeutics.
AB  - OBJECTIVE: To identify young patients with endometrial cancer with potential
      Lynch-related DNA mismatch repair (MMR) protein expression defects and stathmin
      (STMN1) expression (part of the phosphoinositol 3-kinase pathway) and to
      correlate clinical data. METHODS: This retrospective study included women with
      endometrial cancer who were 50 years or younger at diagnosis. Clinical data were
      abstracted from chart review. Immunohistochemistry for MMR protein expression,
      STMN1, and pSTMN1 was performed and univariate analyses performed. RESULTS: The
      mean age of 111 patients was 43 years, and the mean body mass index was 39.6
      kg/m2. The majority of the endometrial cancers were endometrioid histology
      (87.4%), International Federation of Gynecology and Obstetrics stage I (73%) and
      grade 1 (58.6%). Loss of at least one MMR protein on immunohistochemistry was
      identified in 26% to 41% of patients depending on stringency. Women with loss of
      MMR protein expression were compared to women with intact tumor protein
      expression and were less likely to be stage I (58.6% vs 78.0%; P = 0.043), more
      likely to have grade 3 tumors (32.1% vs 13.9%; P = 0.034), had larger tumors (6.2
      vs 3.7 cm; P < 0.001), had positive lymph nodes more often (24.1% vs 3.7%; P <
      0.001), and more often reported a first-degree relative with colon cancer (17.2%
      vs 1.2%; P < 0.001). There were no significant differences in age, weight, body
      mass index, medical comorbidities, recurrence, or survival. Women with high STMN1
      staining had significantly more grade 3 tumors (56.3% vs 15.8%; P = 0.001), more
      stage III/IV disease (37.5% vs 15.8%; P = 0.04), had higher mean percentage of
      myometrial invasion (38.9% vs 16.7%; P = 0.003), and more lymphovascular space
      invasion (43.8% vs 13.7%; P = 0.004). CONCLUSIONS: Clinical factors failed to
      differentiate between patients with intact or missing MMR protein expression,
      which supports universal screening for Lynch-associated protein defects in young
      women with endometrial cancer. Additionally, STMN1 staining may identify more
      aggressive tumors, which might benefit from more aggressive treatments or
      targeted treatment options.

PMID- 23552807
TI  - Villoglandular papillary adenocarcinoma of the cervix: a series of 28 cases
      including two with lymph node metastasis.
AB  - OBJECTIVE: To investigate the clinicopathologic features, the management, and the
      outcome of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix.
      METHODS: A retrospective review of patients' clinical characteristics, pathology,
      and the disease management, together with outcome information. RESULTS: A total
      of 28 patients with VGPA were treated. The median age of the patients was 38
      years with a range of 26 to 65 years. Sixteen of the 21 patients presented with
      abnormal bleeding, and 5 patients had an abnormal Papanicolaou (Pap) test result.
      Nineteen patients had International Federation of Gynecology and Obstetrics stage
      IB disease, and 5 patients had stage IIB disease. Two of 24 patients, where the
      lymph node status was known, had positive nodes. Twenty patients underwent
      different types of radical surgery with or without pelvic radiotherapy, and 8
      patients received platinum-based chemotherapy and pelvic radiotherapy with no
      surgery. The follow-up ranged from 5 to 168 months with a median of 35 months.
      Twenty-one patients are alive with no evidence of recurrent disease, 5 patients
      have died because of the disease recurrence, and 2 patients were lost to follow
      up. The overall and disease-free 5-year survival for these patients was 82% and
      75%, respectively. CONCLUSION: This study confirms the excellent prognosis of
      VGPA overall compared to the common forms of cervical cancer, but the prognosis
      is related to stage and pathology. A large multicenter prospective study is
      warranted to determine the most appropriate treatment for the disease. Until
      then, a meta-analysis on the subject would be of benefit.

PMID- 23552808
TI  - ACP Journal Club. A restrictive transfusion strategy reduced 45-day mortality in
      patients with acute upper GI bleeding.

PMID- 23552809
TI  - Exposure to multiple low-level chemicals in relation to reproductive hormones in
      premenopausal women involved in liquid crystal display manufacture.
AB  - BACKGROUND: Liquid crystal display (LCD) manufacturing involves three fabrication
      processes: array, panel and module processes, which result in different levels of
      volatile organic compound (VOC) exposure. The aim of this study was to assess the
      potential reproductive endocrine effects of occupational exposures during LCD
      manufacturing predictive of menstrual cycles as subclinical markers of female
      reproductive dysfunction effects of low-dose exposures. METHODS: A total of 94
      fabrication workers were followed for one complete menstrual cycle using daily
      urine samples: 23 were from the array, 53 from the panel, and 18 from the module
      work areas. The menstrual cycle characteristics of the study population were
      measured using a self-administered questionnaire. Urine samples were collected
      during the first urination in the morning for at least one complete menstrual
      cycle. The urine was then analyzed to determine the urinary concentrations of
      follicular stimulating hormone (FSH), estrone conjugates (E1C), and pregnanediol
      3-glucuronide (PdG). The results of this analysis were used to assess the
      potential effects of chemical exposure as determined by handheld volatile organic
      compound (VOC) monitors and 24 h canisters. RESULTS: The concentration of total
      VOCs was much higher in the module making area (ND-21,000 ppb) than in panel (ND
      766 ppb) and array (58-1,472 ppb) making areas. The concentrations of ethanol and
      acetone were much higher in the module (1,974.9 and 2,283.2 ppb, respectively)
      and panel (2256.9 and 592.2 ppb, respectively) making areas. Compared to those in
      the array making area, we found that E1C (12.55, 95% confidence interval (CI):
      8.49, 16.61 MUg/mg Cr) and PdG (0.53, 95% CI: 0.29, 0.77 MUg/mg Cr) levels in the
      module group were significantly higher in the early follicular phase; E1C (11.93,
      95% CI: 6.21, 17.65 MUg/mg Cr) and PdG (0.53, 95% CI: 0.29, 0.77 MUg/mg Cr)
      levels were significantly higher in the periovulatory phase; and all the hormone
      levels, FSH (1.48, 95% CI: 0.81, 2.15 MUg/mg Cr), E1C (9.29, 95% CI: 4.92, 13.66
      MUg/mg Cr), and PdG (1.01, 95% CI: 0.42, 1.60 MUg/mg Cr) were also significantly
      higher in the luteal phase. In addition, the FSH (0.89, 95% CI: 0.07, 1.71 MUg/mg
      Cr) level in the panel group was significantly higher but E1C (-4.49, 95% CI: 
      7.90, -1.08 MUg/mg Cr) was lower in the early follicular phase; and E1C (-5.16,
      95% CI: -9.61, -0.71 MUg/mg Cr) level was significantly lower in the
      periovulatory phase. CONCLUSIONS: Our findings add to the evidence that exposure
      to multiple low-level chemicals is associated with modest changes in reproductive
      hormone urinary concentrations in healthy premenopausal women. In addition, the
      FSH (0.89, 95% CI: 0.07, 1.71 MUg/mg Cr) level in the panel group was
      significantly higher but E1C (-4.49, 95% CI: -7.90, -1.08 MUg/mg Cr) lower in the
      early follicular phase; and E1C (-5.16, 95% CI: -9.61, -0.71 MUg/mg Cr) level was
      significantly lower in the periovulatory phase.

PMID- 23552810
TI  - Annoyance and worry in a petrochemical industrial area--prevalence, time trends
      and risk indicators.
AB  - In 1992, 1998, and 2006, questionnaires were sent to stratified samples of
      residents aged 18-75 years living near petrochemical industries (n = 600-800
      people on each occasion) and in a control area (n = 200-1,000). The aims were to
      estimate the long-term prevalence and change over time of annoyance caused by
      industrial odour, industrial noise, and worries about possible health effects,
      and to identify risk indicators. In 2006, 20% were annoyed by industrial odour,
      27% by industrial noise (1-4% in the control area), and 40-50% were worried about
      health effects or industrial accidents (10-20% in the control area). Multiple
      logistic regression analyses revealed significantly lower prevalence of odour
      annoyance in 1998 and 2006 than in 1992, while industrial noise annoyance
      increased significantly over time. The prevalence of worry remained constant.
      Risk of odour annoyance increased with female sex, worry of health effects,
      annoyance by motor vehicle exhausts and industrial noise. Industrial noise
      annoyance was associated with traffic noise annoyance and worry of health effects
      of traffic. Health-risk worry due to industrial air pollution was associated with
      female sex, having children, annoyance due to dust/soot in the air, and worry of
      traffic air pollution.

PMID- 23552811
TI  - Developing the potential of using Galleria mellonella larvae as models for
      studying brain infection by Listeria monocytogenes.

PMID- 23552812
TI  - Risk-reducing appendectomy and the elimination of BRCA1-associated
      intraperitoneal cancer.
AB  - Risk-reducing bilateral salpingo-oophorectomy (RRBSO) and risk-reducing
      mastectomy are widely used for BRCA1 and BRCA2 mutation carriers to reduce the
      risk of ovarian and breast cancer. To our knowledge, no risk-reduction therapy
      has addressed the BCRA1/2 carrier lifetime risk of intra-abdominal peritoneal
      carcinoma from an appendix source. We identified a BRCA1 carrier in a hereditary
      breast and ovarian cancer kindred who developed a low-grade malignant appendiceal
      mucocele 2 years after risk-reducing salpingo-oophorectomy. Our retrospective
      meta-analysis assessed the risk of intraperitoneal appendiceal cancer in BRCA1/2
      carriers after RRBSO to determine whether elective risk-reduction appendectomy
      could reduce the incidence of intraperitoneal cancer. Data sources included the
      case report and 12 reports of BRCA1 and BRCA2 carriers after RRBSO with ovarian,
      fallopian tube, breast, and peritoneal cancer published from January 1, 1985,
      through April 30, 2012. Main outcome measures were nonovarian, non-fallopian
      tube, nonbreast, positive intra-abdominal peritoneal carcinoma in previously
      cancer-free BRCA1/2 carriers after RRBSO. The source of intraperitoneal cancer in
      BRCA1/2 carriers after risk-reducing salpingo-oophorectomy is highly likely the
      appendix. Use of risk-reduction appendectomy with RRBSO in younger BRCA1/2
      carriers may reduce lifetime risk of malignant tumor and eliminate
      intraperitoneal cancer.

PMID- 23552813
TI  - Overcoming specialty bias: another important reason for multidisciplinary
      management of soft tissue sarcoma.

PMID- 23552815
TI  - Exploitation of chick embryo environments to reprogram MYCN-amplified
      neuroblastoma cells to a benign phenotype, lacking detectable MYCN expression.
AB  - Neuroblastoma is a paediatric cancer that arises from the sympathetic ganglia
      (SG) or adrenal gland. Tumours that occur in patients under 18 months of age have
      a particularly good prognosis and frequently undergo spontaneous regression. This
      led to the hypothesis that developmental cues in the youngest patients may prompt
      belated differentiation and/or apoptosis of the tumour cells. To test our
      hypothesis, we have injected MYCN-amplified neuroblastoma cells into the extra
      embryonic veins of chick embryos at embryonic day 3 (E3) and E6 and analysed the
      response of these Kelly cells at E10 and E14. Amplification of the MYCN gene
      occurs in up to 30% of tumours and is normally associated with a very poor
      prognosis. Kelly cells injected at E3 follow neural crest pathways and integrate
      into neural locations such as SG and the enteric nervous system although never
      into the adrenal gland. Additionally they migrate to non-neural locations such as
      the heart, meninges, jaw regions and tail. The cells respond to their respective
      microenvironments and in SG, some cells differentiate, they show reduced cell
      division and crucially all cells have undetectable MYCN expression by E10. In non
      neural locations, cells form more rapidly dividing clumps and continue to express
      MYCN. The downregulation of MYCN is dependent on continuous and direct
      interaction with the sympathetic ganglion environment. We propose that the MYCN
      amplicon in the Kelly cells retains the ability to correctly interpret the
      environmental cues leading to downregulation of MYCN.

PMID- 23552814
TI  - Mathematical modeling of infectious disease dynamics.
AB  - Over the last years, an intensive worldwide effort is speeding up the
      developments in the establishment of a global surveillance network for combating
      pandemics of emergent and re-emergent infectious diseases. Scientists from
      different fields extending from medicine and molecular biology to computer
      science and applied mathematics have teamed up for rapid assessment of
      potentially urgent situations. Toward this aim mathematical modeling plays an
      important role in efforts that focus on predicting, assessing, and controlling
      potential outbreaks. To better understand and model the contagious dynamics the
      impact of numerous variables ranging from the micro host-pathogen level to host
      to-host interactions, as well as prevailing ecological, social, economic, and
      demographic factors across the globe have to be analyzed and thoroughly studied.
      Here, we present and discuss the main approaches that are used for the
      surveillance and modeling of infectious disease dynamics. We present the basic
      concepts underpinning their implementation and practice and for each category we
      give an annotated list of representative works. 

PMID- 23552816
TI  - Periorificial dermatitis and erosive inguinal plaques in a 57-year-old woman.
      Acquired zinc deficiency acrodermatitis enteropathica (ADE).

PMID- 23552819
TI  - QD-filled micelles which combine SPECT and optical imaging with light-induced
      activation of a platinum(IV) prodrug for anticancer applications.
AB  - The fac-[(99m)Tc(OH2)3(CO)3](+) complex reacts with QD-filled micelles to create
      a bimodal SPECT-optical imaging probe which upon visible light irradiation
      generates cisplatin from an inert Pt(IV) prodrug.

PMID- 23552817
TI  - Outcomes of screening mammography by frequency, breast density, and
      postmenopausal hormone therapy.
AB  - IMPORTANCE: Controversy exists about the frequency women should undergo screening
      mammography and whether screening interval should vary according to risk factors
      beyond age. OBJECTIVE: To compare the benefits and harms of screening mammography
      frequencies according to age, breast density, and postmenopausal hormone therapy
      (HT) use. DESIGN: Prospective cohort. SETTING: Data collected January 1994 to
      December 2008 from mammography facilities in community practice that participate
      in the Breast Cancer Surveillance Consortium (BCSC) mammography registries.
      PARTICIPANTS: Data were collected prospectively on 11,474 women with breast
      cancer and 922,624 without breast cancer who underwent mammography at facilities
      that participate in the BCSC. MAIN OUTCOMES AND MEASURES: We used logistic
      regression to calculate the odds of advanced stage (IIb, III, or IV) and large
      tumors (>20 mm in diameter) and 10-year cumulative probability of a false
      positive mammography result by screening frequency, age, breast density, and HT
      use. The main predictor was screening mammography interval. RESULTS: Mammography
      biennially vs annually for women aged 50 to 74 years does not increase risk of
      tumors with advanced stage or large size regardless of women's breast density or
      HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial
      mammography vs annual is associated with increased risk of advanced-stage cancer
      (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI,
      1.37-4.18). Cumulative probability of a false-positive mammography result was
      high among women undergoing annual mammography with extremely dense breasts who
      were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%)
      and was lower among women aged 50 to 74 years who underwent biennial or triennial
      mammography with scattered fibroglandular densities (30.7% and 21.9%,
      respectively) or fatty breasts (17.4% and 12.1%, respectively). CONCLUSIONS AND
      RELEVANCE: Women aged 50 to 74 years, even those with high breast density or HT
      use, who undergo biennial screening mammography have similar risk of advanced
      stage disease and lower cumulative risk of false-positive results than those who
      undergo annual mammography. When deciding whether to undergo mammography, women
      aged 40 to 49 years who have extremely dense breasts should be informed that
      annual mammography may minimize their risk of advanced-stage disease but the
      cumulative risk of false-positive results is high.

PMID- 23552820
TI  - The impact of prenatal alcohol exposure on addiction treatment.
AB  - Fetal alcohol spectrum disorders (FASDs) are conditions caused by prenatal
      alcohol exposure in amounts sufficient to cause permanent deficits in brain
      functioning. Extent of damage largely depends on timing, dose, frequency, and
      pattern of exposure. Timing is especially important because prenatal alcohol
      exposure during critical periods of gestation can affect brain development in
      ways that produce varying patterns of neurocognitive deficits and associated
      adaptive impairments. This article describes some of the more serious
      neurophysiological and neuropsychological sequelae of prenatal alcohol exposure
      that contribute to increased risk for substance abuse problems among people with
      an FASD. We discuss the unique interface between pharmacological treatment and
      FASD, noting that failure to consider the possibility of FASD in treatment
      planning may result in treatment failure and/or relapse. Finally, we present a
      clinical case example and recommend service accommodations to address some of the
      impairments in FASD that limit substance abuse treatment success.

PMID- 23552821
TI  - Eight weeks of exercise training improves fitness measures in methamphetamine
      dependent individuals in residential treatment.
AB  - OBJECTIVES: Physical exercise has been shown to benefit diverse medical and
      behavioral conditions. This study assesses the feasibility and efficacy of an 8
      week endurance and resistance training program on fitness measures in individuals
      undergoing residential treatment for methamphetamine (MA) dependence. METHODS: A
      total of 39 MA-dependent individuals were randomized to 3 days/week of exercise
      training (ET, n = 15) or health education without training (equal attention [EA],
      n = 14) over 8 weeks. Aerobic performance ((Equation is included in full-text
      article.)VO2max) was measured by indirect calorimetry, body composition by
      skinfolds, muscle strength by 1-repetition maximum (1-RM), and endurance at 85%
      of 1-RM for both leg press (LP) and chest press (CP). RESULTS: A total of 29
      individuals completed the study for a 74% adherence rate. Baseline
      characteristics (mean +/- SD) were balanced between groups: age 31 +/- 7 years;
      height = 1.74 +/- 0.07 m; weight 82.0 +/- 15.0 kg. The ET group significantly
      improved (Equation is included in full-text article.)O2max by 0.63 +/- 0.22 L/min
      (+21%), LP strength by 24.4 +/- 5.6 kg (+40%), and CP strength by 20.6 +/- 5.7 kg
      (+49%). The ET group increased LP and CP endurance by 120% and 96%, respectively
      and showed significant reductions in body weight of 1.7 +/- 2.4 kg (-2%), % body
      fat of 2.8 +/- 1.3% (-15%), and fat weight 2.8 +/- 1.8 kg (-18%). All changes
      were significant (P < 0.001) for ET, and no changes were seen for the EA group.
      CONCLUSIONS: Individuals recovering from MA dependence showed substantial
      improvements in aerobic exercise performance, muscle strength and endurance, and
      body composition with ET. These findings demonstrate the feasibility of an ET
      intervention in these participants and also show excellent responsiveness to the
      exercise stimulus resulting in physiological changes that might enhance recovery
      from drug dependency.

PMID- 23552823
TI  - Site-specific peptide and protein immobilization on surface plasmon resonance
      chips via strain-promoted cycloaddition.
AB  - Surface plasmon resonance (SPR) is a powerful label-free diagnostic tool to study
      biomolecular interactions. However, one of the drawbacks of SPR is the lack of
      controlled immobilization of ligands on the sensor surface. We have developed a
      modular platform for the fast, reagent-free and site-specific immobilization of
      azide-containing ligands by strain-promoted cycloaddition onto a cyclooctyne
      modified SPR sensor surface. The usefulness of the concept was shown in a study
      with a papain model system, and up to 150 experiments were performed without loss
      of surface quality. Furthermore, azide-containing green fluorescent protein (GFP)
      was also effectively immobilized. Taken together, cyclooctyne-modified SPR chips
      enable smooth and site-selective immobilization of ligands and prove to be more
      robust than traditionally functionalized systems.

PMID- 23552824
TI  - Smoking, a dangerous habit for the skin.

PMID- 23552825
TI  - The effect of physical exercise on bone density in middle-aged and older men: a
      systematic review.
AB  - Although trials have shown that exercise has positive effects on bone mineral
      density (BMD), the majority of exercise trials have been conducted in older
      women. The aim of this study was to systematically review trials examining the
      effect of weight-bearing and resistance-based exercise modalities on the BMD of
      hip and lumbar spine of middle-aged and older men. Eight electronic databases
      were searched in August 2012. Randomised controlled or controlled trials that
      assessed the effect of weight-bearing and resistance-based exercise interventions
      on BMD measured by dual-energy x-ray absorptiometry, and reported effects in
      middle-aged and older men were included. Eight trials detailed in nine papers
      were included. The interventions included walking (n = 2), resistance training (n
      = 3), walking + resistance training (n = 1), resistance training + impact-loading
      activities (n = 1) and resistance training + Tai Chi (n = 1). Five of the eight
      trials achieved a score of less than 50% on the modified Delphi quality rating
      scale. Further, there was heterogeneity in the type, intensity, frequency and
      duration of the exercise regimens. Effects of exercise varied greatly among
      studies, with six interventions having a positive effect on BMD and two
      interventions having no significant effect. It appears that resistance training
      alone or in combination with impact-loading activities are most osteogenic for
      this population, whereas the walking trials had limited effect on BMD. Therefore,
      regular resistance training and impact-loading activities should be considered as
      a strategy to prevent osteoporosis in middle-aged and older men. High quality
      randomised controlled trials are needed to establish the optimal exercise
      prescription.

PMID- 23552828
TI  - Rapid self-healable poly(ethylene glycol) hydrogels formed by selective metal
      phosphate interactions.
AB  - Rapid self-healable and biocompatible hydrogels were prepared using the selective
      formation of metal-ligand interactions between selected metal ions and phosphate
      end groups of poly(ethylene glycol) (PEG). The phosphate-terminated branch of PEG
      was synthesized via a substitution reaction of the hydroxyl end groups using
      phosphoryl chloride. The gelation and gel properties including rheological
      properties can be tuned by the careful selection of metal ions, branch numbers,
      and temperature. Especially, the gels rapidly formed by trivalent metal ions such
      as Fe(3+), V(3+), Al(3+), Ti(3+), and Ga(3+) have relatively small ionic radii.
      The ligand substitution rates also affected the repeatable autonomic healing
      ability. We have also demonstrated a gel-sol/sol-gel transition by switching the
      redox states of Fe(3+)/Fe(2+) ions. Learning from biological systems, the
      proposed phosphate-metal ion based self-healable hydrogels could become an
      attractive candidate for various biomedical and environmental applications.

PMID- 23552827
TI  - Modulation of the enterohemorrhagic E. coli virulence program through the human
      gastrointestinal tract.
AB  - Enteric pathogens must not only survive passage through the gastrointestinal
      tract but must also coordinate expression of virulence determinants in response
      to localized microenvironments with the host. Enterohemorrhagic Escherichia coli
      (EHEC), a serious food and waterborne human pathogen, is well equipped with an
      arsenal of molecular factors that allows it to survive passage through the
      gastrointestinal tract and successfully colonize the large intestine. This review
      will explore how EHEC responds to various environmental cues associated with
      particular microenvironments within the host and how it employs these cues to
      modulate virulence factor expression, with a view to developing a conceptual
      framework for understanding modulation of EHEC's virulence program in response to
      the host. In vitro studies offer significant insights into the role of individual
      environmental cues but in vivo studies using animal models as well as data from
      natural infections will ultimately provide a more comprehensive picture of the
      highly regulated virulence program of this pathogen. 

PMID- 23552829
TI  - The use of Chitosan to enhance photodynamic inactivation against Candida albicans
      and its drug-resistant clinical isolates.
AB  - Drug-resistant Candida infection is a major health concern among
      immunocompromised patients. Antimicrobial photodynamic inactivation (PDI) was
      introduced as an alternative treatment for local infections. Although Candida
      (C.) has demonstrated susceptibility to PDI, high doses of photosensitizer (PS)
      and light energy are required, which may be harmful to eukaryotic human cells.
      This study explores the capacity of chitosan, a polycationic biopolymer, to
      increase the efficacy of PDI against C. albicans, as well as fluconazole
      resistant clinical isolates in planktonic or biofilm states. Chitosan was shown
      to effectively augment the effect of PDI mediated by toluidine blue O (TBO)
      against C. albicans that were incubated with chitosan for 30 min following PDI.
      Chitosan at concentrations as low as 0.25% eradicated C. albicans; however,
      without PDI treatment, chitosan alone did not demonstrate significant
      antimicrobial activity within the 30 min of incubation. These results suggest
      that chitosan only augmented the fungicidal effect after the cells had been
      damaged by PDI. Increasing the dosage of chitosan or prolonging the incubation
      time allowed a reduction in the PDI condition required to completely eradicate C.
      albicans. These results clearly indicate that combining chitosan with PDI is a
      promising antimicrobial approach to treat infectious diseases.

PMID- 23552830
TI  - Characterization and expression of the gene encoding En-MAPK1, an intestinal cell
      kinase (ICK)-like kinase activated by the autocrine pheromone-signaling loop in
      the Polar Ciliate, Euplotes nobilii.
AB  - In the protozoan ciliate Euplotes, a transduction pathway resulting in a
      mitogenic cell growth response is activated by autocrine receptor binding of cell
      type-specific, water-borne signaling protein pheromones. In Euplotes raikovi, a
      marine species of temperate waters, this transduction pathway was previously
      shown to involve the phosphorylation of a nuclear protein kinase structurally
      similar to the intestinal-cell and male germ cell-associated kinases described in
      mammals. In E. nobilii, which is phylogenetically closely related to E. raikovi
      but inhabits Antarctic and Arctic waters, we have now characterized a gene
      encoding a structurally homologous kinase. The expression of this gene requires
      +1 translational frameshifting and a process of intron splicing for the
      production of the active protein, designated En-MAPK1, which contains amino acid
      substitutions of potential significance for cold-adaptation.

PMID- 23552831
TI  - Synthesis and characterization of naphthalenediimide-functionalized flavin
      derivatives.
AB  - Two acceptor-acceptor dyads have been synthesized featuring a flavin moiety and a
      naphthalenediimide (NDI) unit. The NDI unit is linked to the flavin through a
      short spacer group via either the N(3) or N(10) positions of the flavin. We have
      investigated the UV-Vis and redox properties of these multi-electron accepting
      systems which indicate that these materials display the collective properties of
      their component systems. Fluorescence spectroscopy measurements have revealed
      that their emission properties are dominated by the flavin unit.

PMID- 23552832
TI  - Soluble receptor for advanced glycation end-product (sRAGE)/pentosidine ratio: a
      potential risk factor determinant for type 2 diabetic retinopathy.
AB  - This study aims to investigate potential diabetic retinopathy (DR) risk factors
      by evaluating the circulating levels of pentosidine, soluble receptor for
      advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP)
      as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities
      in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without
      retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited.
      Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and
      GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD
      activity measurement. DNR and DR patients showed significantly higher levels of
      plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared
      to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly
      lower than the ratio detected in DNR patients. Proliferative DR patients had
      significantly higher levels of plasma pentosidine, sRAGE, AOPP and
      sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level,
      long duration of diabetes and low sRAGE/pentosidine ratio were determined as the
      risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve
      as a risk factor determinant for type 2 DR as it has a positive correlation with
      the severity of DR.

PMID- 23552833
TI  - ACP Journal Club. Aliskiren increased adverse events in patients with diabetes
      and kidney disease who were receiving ACE inhibitors or ARBs.

PMID- 23552834
TI  - TRIPS-plus and access to medicines in China.
AB  - Ample evidence shows that Trade-related aspects of intellectual property rights
      (TRIPS)-plus provisions have seriously affected access to and availability of
      drugs in the developing countries. In recent years, developed countries have
      pressured many developing countries to implement TRIPS with stronger intellectual
      property (IP) protection than required by the TRIPS Agreement. The stronger
      provisions are called TRIPS-Plus provisions. This article focuses on IP and the
      health implications of limited access to medicines in China, explores the TRIPS
      plus arrangements in Chinese IP laws and regulations, and makes suggestions for
      China's negotiation strategy in resisting pressure from developed countries to
      tighten IP laws and regulations.

PMID- 23552835
TI  - Effect of topical tafluprost on optic nerve head blood flow in patients with
      myopic disc type.
AB  - PURPOSE: To investigate the effect of topical tafluprost on optic disc blood flow
      in patients with myopic disc. MATERIALS AND METHODS: Forty-eight eyes in 24
      patients with a myopic disc type (oval shaped) optic disc tilted to the temporal,
      with a crescent peripapillary atrophy were included in this study. Twenty-eight
      eyes were diagnosed as normal tension glaucoma and 20 eyes were in normal
      subjects. None had any treatment for glaucoma. Average age was 45.3+/-11.9 years.
      One eye was treated with topical tafluprost and the fellow eye served as the
      control. Ocular blood flow was measured by laser speckle flowgraphy (LSFG-NAVI)
      at 30, 60, 90, and 120 minutes after tafluprost administration, and the mean blur
      rate (MBR) on the optic disc was analyzed. Blood pressure and intraocular
      pressure (IOP) were recorded. RESULTS: In all subjects, topical tafluprost (a)
      significantly reduced IOP versus baseline from 60 minutes after treatment
      (baseline: 15.2+/-3.4 mm Hg, 60 min: 13.3+/-3.2 mm Hg, P=0.001, 90 min: 13.3+/
      3.6 mm Hg, P=0.002, 120 min: 13.7+/-3.4 mm Hg, P=0.007); and (b) significantly
      increased the MBR versus baseline (60 min: +4.3+/-6.6%, P=0.008, 90 min: +5.0+/
      4.9%, P<0.001, 120 min: +6.7+/-7.0%, P<0.001). CONCLUSIONS: Topical tafluprost
      increased MBR in the optic nerve head and significantly reduced IOP, effects that
      may represent beneficial treatment for glaucoma patients with a myopic disc type.

PMID- 23552836
TI  - Identifying content for the glaucoma-specific item bank to measure quality-of
      life parameters.
AB  - PURPOSE: Patient-reported outcomes (PROs) have become essential clinical trial
      end points. However, a comprehensive, multidimensional, patient-relevant, and
      precise glaucoma-specific PRO instrument is not available. Therefore, the purpose
      of this study was to identify content for a new, glaucoma-specific, quality-of
      life (QOL) item bank. METHODS: Content identification was undertaken in 5 phases:
      (1) identification of extant items in glaucoma-specific instruments and the
      qualitative literature; (2) focus groups and interviews with glaucoma patients;
      (3) item classification and selection; (4) expert review and revision of items;
      and (5) cognitive interviews with patients. RESULTS: A total of 737 unique items
      (extant items from PRO instruments, 247; qualitative articles, 14 items; focus
      groups and semistructured interviews, 476 items) were identified. These items
      were classified into 10 QOL domains. Four criteria (item redundancy, item
      inconsistent with domain definition, item content too narrow to have wider
      applicability, and item clarity) were used to remove and refine the items. After
      the cognitive interviews, the final minimally representative item set had a total
      of 342 unique items belonging to 10 domains: activity limitation (88), mobility
      (20), visual symptoms (19), ocular surface symptoms (22), general symptoms (15),
      convenience (39), health concerns (45), emotional well-being (49), social issues
      (23), and economic issues (22). CONCLUSIONS: The systematic content
      identification process identified 10 QOL domains, which were important to
      patients with glaucoma. The majority of the items were identified from the
      patient-specific focus groups and semistructured interviews suggesting that the
      existing PRO instruments do not adequately address QOL issues relevant to
      individuals with glaucoma.

PMID- 23552837
TI  - Womb to grow.

PMID- 23552838
TI  - Epigenetic control of metastasis-associated protein 1 gene expression by
      hepatitis B virus X protein during hepatocarcinogenesis.
AB  - Expression of metastasis-associated protein 1 (MTA1) gene correlates with the
      degree of invasion and metastasis in hepatocellular carcinoma (HCC). Expression
      of MTA1 is induced by hepatitis B virus X protein (HBx); however, little is known
      about the transcriptional regulation of MTA1 gene expression. Here, we report
      that the 5'-flanking region of the human MTA1 promoter contains two CpG islands.
      Transient expression of HBx in Chang liver cells increased the methylation of the
      CpG island1 from 18 to 49% when measured by bisulfite-modified direct sequencing.
      Chromatin immunoprecipitation showed that HBx recruited DNA methyltransferase 3a
      (DNMT3a) and DNMT3b to the CpG island1. In silico analysis of CpG island1
      predicted the existence of putative p53-binding sequences. p53 was pulled down by
      a DNA probe encoding the p53-binding sequences but not by the methylated DNA
      probe. The mouse MTA1 promoter also contains a CpG island encoding a p53-binding
      sequence of which p53 binding was decreased in the presence of HBx, and the
      expression of MTA1 and DNMT3 was increased in the liver of HBx-transgenic mice.
      Comparison of MTA1 and DNMT3a expression in the human normal liver and HCC
      specimens produced a significant correlation coefficient >0.5 (r=0.5686,
      P=0.0001) for DNMT3a, and a marginally significant coefficient (r=0.3162,
      P=0.0103) for DNMT3b. These data show that HBx induces methylation of CpG island
      in the MTA1 promoter, which interferes with DNA binding of p53 in the specific
      DNA region. This result may explain the molecular mechanism responsible for the
      induction of MTA1 gene expression by HBx.

PMID- 23552839
TI  - Disruption of Abi1/Hssh3bp1 expression induces prostatic intraepithelial
      neoplasia in the conditional Abi1/Hssh3bp1 KO mice.
AB  - Prostate cancer is one of the leading causes of cancer-related deaths in the
      United States and a leading diagnosed non-skin cancer in American men. Genetic
      mutations underlying prostate tumorigenesis include alterations of tumor
      suppressor genes. We tested the tumor suppressor hypothesis for ABI1/hSSH3BP1 by
      searching for gene mutations in primary prostate tumors from patients, and by
      analyzing the consequences of prostate-specific disruption of the mouse
      Abi1/Hssh3bp1 ortholog. We sequenced the ABI1/hSSH3BP1 gene and identified
      recurring mutations in 6 out of 35 prostate tumors. Moreover, complementation and
      anchorage-independent growth, proliferation, cellular adhesion and xenograft
      assays using the LNCaP cell line, which contains a loss-of-function Abi1
      mutation, and a stably expressed wild-type or mutated ABI gene, were consistent
      with the tumor suppressor hypothesis. To test the hypothesis further, we
      disrupted the gene in the mouse prostate by breeding the Abi1 floxed strain with
      the probasin promoter-driven Cre recombinase strain. Histopathological evaluation
      of mice indicated development of prostatic intraepithelial neoplasia (PIN) in
      Abi1/Hssh3bp1 knockout mouse as early as the eighth month, but no progression
      beyond PIN was observed in mice as old as 12 months. Observed decreased levels of
      E-cadherin, beta-catenin and WAVE2 in mouse prostate suggest abnormal cellular
      adhesion as the mechanism underlying PIN development owing to Abi1 disruption.
      Analysis of syngeneic cell lines point to the possibility that upregulation of
      phospho-Akt underlies the enhanced cellular proliferation phenotype of cells
      lacking Abi1. This study provides proof-of-concept for the hypothesis that Abi1
      downregulation has a role in the development of prostate cancer.

PMID- 23552840
TI  - Overexpressing the CCL2 chemokine in an epithelial ovarian cancer cell line
      results in latency of in vivo tumourigenicity.
AB  - The frequent loss of heterozygosity of chromosome (Chr) 17 in epithelial ovarian
      cancer (EOC), particularly high-grade ovarian serous carcinomas (HGOSCs), has
      been attributed to the disruption of known tumour suppressor genes, such as TP53
      (17p13), as well as other genes on this chromosome that alone or in combination
      have a role in EOC. In a transcriptome analysis of Chr17 genes, we observed
      significant underexpression of the chemokine CCL2 (17q12) in a small set of HGOSC
      samples relative to normal ovarian surface epithelial cells and a significant
      upregulation of CCL2 in the TP53-mutated OV-90 EOC cell line rendered non
      tumourigenic as a consequence of genetic manipulation. Here, we report that
      overexpressing CCL2 in OV-90 resulted in latency of tumour formation at
      intraperitoneal (i.p.) but not subcutaneous sites in a mouse xenograft model.
      Overexpressing CCL2 affected cell morphology and exerted modest, but not
      significant effects on cell viability, colony formation and cell migration. We
      report significant underexpression of CCL2 by transcriptome analysis (P=0.015)
      and by immunohistochemistry in 77% of HGOSC samples (n=65). Absent or a very low
      level of protein expression by immunohistochemistry was also observed in 71% of
      additional HGOSC samples (n=122). However, CCL2 protein expression did not
      significantly correlate with overall or disease-free survival. The epithelial
      cells of normal fallopian tubes, a purported origin of HGOSC, exhibited
      expression of CCL2 protein by immunohistochemistry. Our results affirm that CCL2
      underexpression is a significant feature of HGOSC samples, and that CCL2
      overexpression in an EOC cell line model affects tumourigenic potential in the
      i.p. setting.

PMID- 23552841
TI  - Comparative analysis of SV40 17kT and LT function in vivo demonstrates that LT's
      C-terminus re-programs hepatic gene expression and is necessary for tumorigenesis
      in the liver.
AB  - Transformation by Simian Virus 40 (SV40) large T antigen (LT) is mediated in
      large part by its interaction with a variety of cellular proteins at distinct
      binding domains within LT. While the interaction of LT's N-terminus with the
      tumor suppressor Rb is absolutely required for LT-dependent transformation, the
      requirement for the interaction of LT's C-terminus with p53 is less clear and
      cell- and context-dependent. Here, we report a line of transgenic mice expressing
      a doxycycline-inducible liver-specific viral transcript that produces abundant
      17kT, a naturally occurring SV40 early product that is co-linear with LT for the
      first 131 amino acids and that binds to Rb, but not p53. Comparative analysis of
      livers of transgenic mice expressing either 17kT or full length LT demonstrates
      that 17kT stimulates cell proliferation and induces hepatic hyperplasia but is
      incapable of inducing hepatic dysplasia or promoting hepatocarcinogenesis. Gene
      expression profiling demonstrates that 17kT and LT invoke a set of shared
      molecular signatures consistent with the action of LT's N-terminus on Rb-E2F
      mediated control of hepatocyte transcription. However, 17kT also induces a unique
      set of genes, many of which are known transcriptional targets of p53, while LT
      actively suppresses them. LT also uniquely deregulates the expression of a subset
      of genes within the imprinted network and rapidly re-programs hepatocyte gene
      expression to a more fetal-like state. Finally, we provide evidence that the
      LT/p53 complex provides a gain-of-function for LT-dependent transformation in the
      liver, and confirm the absolute requirement for LT's C-terminus for liver tumor
      development by demonstrating that phosphatase and tensin homolog (PTEN)
      deficiency readily cooperates with LT, but not 17kT, for tumorigenesis. These
      results confirm independent and inter-dependent functions for LT's N- and C
      terminus and emphasize differences in the requirements for LT's C-terminus in
      cell-type dependent transformation.

PMID- 23552842
TI  - Ultrasound bladder vibrometry method for measuring viscoelasticity of the bladder
      wall.
AB  - Increase in bladder stiffness could be associated with various pathophysiologic
      conditions. Measuring bladder viscoelasticity could be an important step towards
      understanding various disease processes and improving patient care. Here, we
      introduce ultrasound bladder vibrometry (UBV), a novel method for rapid and
      noninvasive measurement of bladder wall viscoelasticity. UBV uses acoustic
      radiation force to excite mechanical waves in the bladder wall and track the
      motion using ultrasound pulse-echo techniques. Fourier domain analysis of the
      tissue motion versus time is used to calculate the phase velocity dispersion
      (change of phase velocity as a function of frequency). The measured phase
      velocity dispersion is fit with the antisymmetric Lamb wave model to estimate
      tissue elasticity and viscosity. We used finite element analysis of viscoelastic
      plate deformation to investigate the effect of curvature on Lamb wave dispersion
      and showed that the effects of curvature are negligible. The feasibility of the
      UBV technique was demonstrated in ex vivo and in vivo settings. Elasticity and
      viscosity of excised pig at various filling volumes (V) and pressures (p) were
      found to be u1 = 9.6 kPa and u2 = 0.2 Pa s (V = 187 ml and p = 8.6 mmHg), u1 =
      48.7 kPa and u2 = 3.5 Pa s (V = 267 ml and p = 17.6 mmHg), and u1 = 106.9 kPa and
      u2 = 1.5 Pa s (V = 327 ml and p = 27.6 mmHg) respectively. Transabdominal
      measurements in an anesthetized pig found values of bladder elasticity u1 = 26.1
      kPa and viscosity u2 = 0.9 Pa s and demonstrate the ability of UBV to perform in
      vivo measurements. The results presented in this paper introduce a novel
      technique for measuring mechanical properties of the bladder and lay the
      foundation for further investigation of the effects of pathology on bladder
      viscoelasticity.

PMID- 23552843
TI  - Intracellular cleavable poly(2-dimethylaminoethyl methacrylate) functionalized
      mesoporous silica nanoparticles for efficient siRNA delivery in vitro and in
      vivo.
AB  - A low cytotoxicity and high efficiency delivery system with the advantages of low
      cost and facile fabrication is needed for the application of small interfering
      RNA (siRNA) delivery both in vitro and in vivo. For these prerequisites, cationic
      polymer-mesoporous silica nanoparticles (ssCP-MSNs) were prepared by surface
      functionalized mesoporous silica nanoparticles with disulfide bond cross-linked
      poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). In vitro and in vivo
      evaluations were performed. The synthesized ssCP-MSNs are 100-150 nm in diameter
      with a pore size of 10 nm and a positively charged surface with a high zeta
      potential of 27 mV. Consequently, the ssCP-MSNs showed an excellent binding
      capacity for siRNA, and an enhancement in the cell uptake and cytosolic
      availability of siRNA. Furthermore, the intracellular reducing cleavage of the
      disulfide bonds cross-linking the PDMAEMA segments led to intracellular cleavage
      of PDMAEMA from ssCP-MSNs, which facilitated the intracellular triggered release
      of siRNA. Therefore, promoted RNA interference was observed in HeLa-Luc cells,
      which was equal to that of Lipofectamine 2000. Significantly, compared to
      Lipofectamine 2000, the ssCP-MSNs were more biocompatible, with low cytotoxicity
      (even non-cytotoxicity) and promotion of cell proliferation to HeLa-Luc cells.
      The in vivo systemic distribution studies certified that ssCP-MSNs/siRNA could
      prolong the duration of siRNA in vivo, and that they accumulated in the adrenal
      gland, liver, lung, spleen, kidney, heart and thymus after intravenous injection.
      Encouragingly, with the ability to deliver siRNA to a tumor, ssCP-MSNs/siRNA
      showed a tumor suppression effect in the HeLa-Luc xenograft murine model after
      intravenous injection. Therefore, the ssCP-MSNs cationic polymer-mesoporous
      silica nanoparticles with low cytotoxicity are promising for siRNA delivery.

PMID- 23552844
TI  - MOF@activated carbon: a new material for adsorption of aldicarb in biological
      systems.
AB  - A new composite was synthesized by the hydrothermal method using a 3D
      coordination network [Ln2(C4H4O4)3(H2O)2].H2O (Ln = Eu and Tb) and activated
      carbon. The coordination network is formed within the pores of the charcoal,
      allowing for the use of this material as a detoxifying agent. 

PMID- 23552846
TI  - Stability-indicating LC-UV method for the determination of eszopiclone and
      degradation impurities in tablet dosage form.
AB  - A sensitive, stability-indicating reversed-phase high-performance liquid
      chromatographic method was developed for the determination of eszopiclone and
      related impurities in tablet dosage form. The chromatographic separation was
      achieved on an Inertsil C18 column (250 * 4.6 mm, 5 um), using a mobile phase
      consisting of 0.05M monobasic sodium phosphate buffer containing 0.8% sodium
      lauryl sulfate (pH 3.5) and acetonitrile in the ratio of 60:40 (v/v), at a flow
      rate of 1.5 mL/min and temperature of 40 degrees C. Quantification was achieved
      with photodiode array detection at 303 nm. The described method showed excellent
      linearity over a range of limits of quantification to 4.8 ug/mL (150% of
      specification limit; i.e., 3.2 ug/mL). The drug product was subjected to the
      stress conditions of oxidative, acid, base, thermal and photolytic degradation.
      Eszopiclone degradation was observed in acid hydrolysis, base hydrolysis and
      peroxide stress conditions. Eszopiclone was stable in thermal and photolytic
      degradation conditions. The developed method is simple, selective and accurate
      for the quantification of impurities and degradation products of eszopiclone in
      tablet dosage form. 

PMID- 23552847
TI  - Isolation of liquiritigenin-4'-apiosyl-glucoside and liquiritin from the root of
      Glycyrrhiza uralensis by high-performance centrifugal partition chromatography.
AB  - High-performance centrifugal partition chromatography (HPCPC) combined with
      ultraviolet detection was employed for the separation and purification of
      flavonoids from Glycyrrhiza. At the detection wavelength of 276 nm, two
      flavonoids, liquiritigenin-4'-apiosyl-glucoside and liquiritin, were successfully
      separated by HPCPC with an optimized two-phase solvent system composed of ethyl
      acetate-ethanol-water (1:0.1:1, v/v/v). The purity of these compounds was 95.0
      and 97.1%, respectively, as determined by high-performance liquid chromatography.
      Their structures were identified by electrospray ion source mass spectroscopy
      (ESI-MS(n)) in the negative ion mode. 

PMID- 23552848
TI  - Indomethacin for refractory infantile eosinophilic pustular folliculitis.

PMID- 23552850
TI  - Influence of race on the management of lower extremity ischemia:
      revascularization vs amputation.
AB  - IMPORTANCE: Among patients presenting with critical lower extremity ischemia, it
      has been previously documented that white individuals are more likely to undergo
      revascularization than nonwhite individuals, with the disparity largely
      attributed to differences in resources and access to care. OBJECTIVE: To
      investigate the amputation disparity between white and nonwhite patients with
      critical lower extremity ischemia in more detail using a larger data set than
      previous studies, with a focus on the role of confounding factors such as access
      and hospital resources. DESIGN, SETTING, AND PATIENTS: All hospital discharge
      records from the Nationwide Inpatient Sample of adult patients with the primary
      diagnosis of critical lower extremity ischemia from 2002-2008 were examined in
      detail using multiple logistic regression (n = 774,399). MAIN OUTCOMES AND
      MEASURES: Rates of amputation and revascularization for peripheral vascular
      disease across race/ethnicity. RESULTS: Controlling for confounding factors,
      black patients were found to have 1.77 times the odds of receiving an amputation
      compared with white patients (95% CI, 1.72-1.84; P < .001). Further analysis
      revealed the black to white odds ratio paradoxically increased with increasing
      revascularization capacity of the presenting hospital, from a low of 1.43 (95%
      CI, 1.23-1.65) to a high of 1.98 (95% CI, 1.83-2.24). The amputation disparity
      also paradoxically increased for patients living in wealthier zip codes.
      CONCLUSIONS AND RELEVANCE: Black patients have greater odds of undergoing
      amputation than white patients, even after correcting for an array of confounding
      parameters. Contrary to current beliefs that the disparity is mainly secondary to
      differences in access, this study found that the disparity was magnified in
      settings where resources were greatest. Whether the explanation lies primarily in
      patient-specific, physician-specific, or institutional-specific factors remains
      to be determined but is critical to better understanding our health care system
      and maintaining approaches that are consistently fair and equitable.

PMID- 23552851
TI  - Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt
      and ERK and JNK signaling pathways in human lung cancer cell lines.
AB  - Our previous study has revealed that dioscin, a compound with anti-inflammatory,
      lipid-lowering, anticancer and hepatoprotective effects, may induce autophagy in
      hepatoma cells. Autophagy is a lysosomal degradation pathway that is essential
      for cell survival and tissue homeostasis. In this study, the role of autophagy
      and related signaling pathways during dioscin-induced apoptosis in human lung
      cancer cells was investigated. Results from 4'-6-diamidino-2-phenylindole and
      annexin-V/PI double-staining assay showed that caspase-3- and caspase-8
      dependent, and dose-dependent apoptoses were detected after a 24-h dioscin
      treatment. Meanwhile, autophagy was detected as early as 12 h after an exposure
      to low-dose dioscin, as indicated by an up-regulated expression of LC3-II and
      beclin-1 proteins. Blockade of autophagy with bafilomycin A1 or 3-methyladenine
      sensitized the A549 and H1299 cells to apoptosis. Treatment of A549 and H1299
      cells with dioscin caused a dose-dependent increase in ERK1/2 and JNK1/2
      activity, accompanied with a decreased PI3K expression and decreased
      phosphorylation of Akt and mTOR. Taken together, this study demonstrated for the
      first time that autophagy occurred earlier than apoptosis during dioscin-induced
      human lung cancer cell line apoptosis. Dioscin-induced autophagy via ERK1/2 and
      JNK1/2 pathways may provide a protective mechanism for cell survival against
      dioscin-induced apoptosis to act as a cytoprotective reaction.

PMID- 23552852
TI  - Effects of mixtures of azole fungicides in postimplantation rat whole-embryo
      cultures.
AB  - The effect of mixtures of azole fungicides on development of postimplantation rat
      whole-embryos cultured in vitro has been tested. On the basis of bench mark dose
      (BMD) modeling of the in vitro effect in rat embryo, the potency of 7 azoles was
      determined and compared. Then, relative potency factors have been derived based
      on either the NOAEL or on the BMD curve. Alternatively, each compound was used as
      index compound (IC), and IC-equivalent concentrations have been calculated for
      each mixture. Expected effects of such IC-equivalent concentrations of the
      mixture were derived from the appropriate BMD curve. Test mixture includes the
      agrochemicals triadimefon and imazalil (MIX2) or triadimefon, imazalil, and the
      clinically used fluconazole (MIX3) at their previously determined no-effect
      concentration, corresponding to approximately a benchmark response of 5-10 %.
      Subsequently, we tested the effect of a mixture of the agrochemicals triadimefon,
      imazalil, triadimenol, cyproconazole, tebuconazole, and flusilazole (MIX6) at
      concentration levels derived from their established human acceptable daily
      intake. MIX6 was also added with fluconazole at concentration levels indicated as
      the minimum therapeutically effective plasmatic concentration (MIX7A) or ten
      times this level (MIX7B). Generally, the experimental response was higher than
      the estimated one, by a factor of 2-6. Our data suggest that it is in principle
      correct to assume that azoles act as teratogens via a common mode of action and
      therefore should be grouped together for risk assessment. The synergistic effect
      needs to be confirmed with more combinations of concentrations/compounds in vitro
      and with specific in vivo experiments.

PMID- 23552854
TI  - [Lagophthalmos and ectropion of the upper eyelids in congenital ichthyosis].
AB  - This report concerns the case of a 10-year-old female patient with congenital
      ichthyosis who developed bilateral ectropion of the upper eyelids resulting in
      massive ocular surface alterations due to lagophthalmos. A complex surgical
      approach with partial excision, tarsal strip refixation and a free skin graft led
      to normalization of the eyelid positioning and healing of the ocular surface. 

PMID- 23552853
TI  - Effects of cannabinoids and related fatty acids upon the viability of P19
      embryonal carcinoma cells.
AB  - Compounds acting on the cannabinoid (CB) receptors are involved in the control of
      cell fate, and there is an emerging consensus that CBs have anticancer effects.
      However, the CB-mediated effects are contradictory since some studies suggest
      stimulatory effects on cancer cell proliferation, and CBs have been shown to
      stimulate both proliferation and differentiation of other mitotic cells such as
      stem and progenitor cells. In this study, the concentration-dependent effects of
      synthetic and endogenous CBs on the viability of mouse P19 embryonal carcinoma
      (EC) cells have been examined by using fluorescence assays of cell membrane
      integrity, cell proliferation, oxidative stress, and detection of apoptosis and
      necrosis. All compounds examined produced a concentration-dependent decrease in
      cell viability in the micromolar range, with the potent CB receptor agonist HU
      210 and the enantiomer HU 211 (with no CB receptor activity) being the most
      potent compounds examined with apparent IC50 values of 1 and 0.6 MUM,
      respectively. The endogenous CB anandamide showed similar potency and efficacy as
      structurally related polyunsaturated fatty acids with no reported activity at the
      CB receptors. The rapid (within hours) decrease in cell viability induced by the
      examined CBs suggests cytocidal rather than antiproliferative effects and is
      dependent on the plating cell population density with the highest toxicity around
      100 cells/mm(2). The CB-induced cytotoxicity, which appears to involve CB
      receptors and the sphingomyelin-ceramide pathway, is a mixture of both apoptosis
      and necrosis that can be blocked by the antioxidants alpha-tocopherol and N
      acetylcysteine. In conclusion, both synthetic and endogenous CBs produce
      seemingly unspecific cytotoxic effects in the P19 EC cells.

PMID- 23552855
TI  - [Chronic uveitis with secondary glaucoma?].

PMID- 23552856
TI  - [Opacification of an intraocular lens: calcification of hydrophilic intraocular
      lenses after gas tamponade of the anterior chamber].
AB  - A patient with endothelial dystrophy was treated with Descemet stripping
      automated endothelial keratoplasty (DSAEK) combined with cataract extraction and
      implantation of a hydrophilic intraocular lens (IOL, Lentis-L312, Oculentis) but
      visual acuity dropped from 0.15 logMAR to 0.52 logMAR 18 months later due to
      calcification of the IOL. With new methods of lamellar corneal transplantation
      being used more frequently the number of necessary anterior chamber tamponades
      with air/gas are increasing. In cataract cases in which a gas tamponade and
      transplantation might be necessary later on (cornea guttata), hydrophilic IOLs
      should be avoided.

PMID- 23552857
TI  - [Iris tumor of unknown origin].
AB  - A 51-year-old woman presented with a non-specific tumor of the iris and
      intraocular inflammation of the left eye. The patient had a history of surgery
      for metastatic bowel cancer and was on chemotherapy. The lesion was excised and
      was found to contain fungal spores and hyphae. Microbiological testing identified
      growth of Candida albicans and the patient was treated with local and systemic
      voriconazole. After combined vitrectomy with cataract surgery, the patient's
      condition improved.

PMID- 23552858
TI  - PodNet, a protein-protein interaction network of the podocyte.
AB  - Interactions between proteins crucially determine cellular structure and
      function. Differential analysis of the interactome may help elucidate molecular
      mechanisms during disease development; however, this analysis necessitates
      mapping of expression data on protein-protein interaction networks. These
      networks do not exist for the podocyte; therefore, we built PodNet, a literature
      based mouse podocyte network in Cytoscape format. Using database protein-protein
      interactions, we expanded PodNet to XPodNet with enhanced connectivity. In order
      to test the performance of XPodNet in differential interactome analysis, we
      examined podocyte developmental differentiation and the effect of cell culture.
      Transcriptomes of podocytes in 10 different states were mapped on XPodNet and
      analyzed with the Cytoscape plugin ExprEssence, based on the law of mass action.
      Interactions between slit diaphragm proteins are most significantly upregulated
      during podocyte development and most significantly downregulated in culture. On
      the other hand, our analysis revealed that interactions lost during podocyte
      differentiation are not regained in culture, suggesting a loss rather than a
      reversal of differentiation for podocytes in culture. Thus, we have developed
      PodNet as a valuable tool for differential interactome analysis in podocytes, and
      we have identified established and unexplored regulated interactions in
      developing and cultured podocytes. 

PMID- 23552859
TI  - Identifying renal medullary neighborhoods--when do distances matter?

PMID- 23552860
TI  - Protective effects of Rho kinase inhibitor fasudil on rats with chronic kidney
      disease.
AB  - The protective effects of Rho kinase inhibitor fasudil against renal diseases
      have recently been reported. We compared the therapeutic effects of fasudil on
      the spontaneously hypercholesterolemic (SHC) rat, a model of chronic kidney
      disease (CKD) with proteinuria, with those of the angiotensin receptor blocker
      olmesartan (OL) by paying attention to the proteinuria and the macrophage
      phenotype. SHC rats were allocated to six treatment groups: a vehicle (Ve) group,
      a low-dose fasudil (FL) group, a high-dose fasudil (FH) group, an OL group, a
      combination of low-dose fasudil and OL (CL) group, and a combination of high-dose
      fasudil and OL (CH) group. Sprague-Dawley rats treated with vehicle served as a
      control (n = 7/each). The rats were treated for 24 wk. Compared with the Ve
      group, proteinuria was significantly decreased in the FH, OL, and CL groups, and
      it completely disappeared in the CH group. Glomerular stainings of nephrin and F
      actin were focally impaired in the Ve group but were restored in the CH group.
      Western blotting showed that the CH group had significantly increased renal
      nephrin expression compared with the Ve group. Interstitial infiltration of
      macrophages was significantly increased in the Ve group, which was significantly
      attenuated in all treatment groups. The ratio of CD206 (M2 macrophage marker) to
      CD68 mRNA was significantly greater in the CH group than in the Ve group. These
      results indicate that fasudil with OL reduces proteinuria by protecting podocyte
      integrity and alters the interstitial macrophage density/phenotype, thereby
      exerting renoprotective effects against CKD.

PMID- 23552861
TI  - Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain
      normal sodium balance and blood pressure.
AB  - Ubiquitylation plays an important role in the control of Na+ homeostasis by the
      kidney. It is well established that the epithelial Na+ channel ENaC is regulated
      by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression
      and activity. Ubiquitylation can be reversed by the action of deubiquitylating
      enzymes (DUBs). One such DUB, USP2-45, was identified previously as an
      aldosterone-induced protein in the kidney and is also a circadian output gene. In
      heterologous expression systems, USP2-45 binds to ENaC, deubiquitylates it, and
      enhances channel density and activity at the cell surface. Because the role of
      USP2-45 in renal Na+ transport had not been studied in vivo, we investigated here
      the effect of Usp2 gene inactivation in this process. We demonstrate first that
      USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did
      not show any differences from wild-type littermates with respect to the diurnal
      control of Na+ or K+ urinary excretion and plasma levels either on a standard
      diet or after acute and chronic changes to low- and high-Na+ diets, respectively.
      Moreover, they had similar aldosterone levels on either a low- or high-Na+ diet.
      Blood pressure measurements using telemetry did not reveal variations compared
      with control mice. Usp2-KO mice did not display alterations in expression of
      genes involved in sodium homeostasis or the ubiquitin system, as evidenced by
      transcriptome analysis in the kidney. Our data suggest that USP2 does not play a
      primary role in the control of Na+ balance or blood pressure.

PMID- 23552862
TI  - Movement of NH3 through the human urea transporter B: a new gas channel.
AB  - Aquaporins and Rh proteins can function as gas (CO2 and NH3) channels. The
      present study explores the urea, H2O, CO2, and NH3 permeability of the human urea
      transporter B (UT-B) (SLC14A1), expressed in Xenopus oocytes. We monitored urea
      uptake using [14C]urea and measured osmotic water permeability (Pf) using video
      microscopy. To obtain a semiquantitative measure of gas permeability, we used
      microelectrodes to record the maximum transient change in surface pH (DeltapHS)
      caused by exposing oocytes to 5% CO2/33 mM HCO3- (pHS increase) or 0.5 mM
      NH3/NH4+ (pHS decrease). UT-B expression increased oocyte permeability to urea by
      >20-fold, and Pf by 8-fold vs. H2O-injected control oocytes. UT-B expression had
      no effect on the CO2-induced DeltapHS but doubled the NH3-induced DeltapHS.
      Phloretin reduced UT-B-dependent urea uptake (Jurea*) by 45%, Pf* by 50%, and (-
      DeltapHS*)NH3 by 70%. p-Chloromercuribenzene sulfonate reduced Jurea* by 25%, Pf*
      by 30%, and (DeltapHS*)NH3 by 100%. Molecular dynamics (MD) simulations of
      membrane-embedded models of UT-B identified the monomeric UT-B pores as the main
      conduction pathway for both H2O and NH3 and characterized the energetics
      associated with permeation of these species through the channel. Mutating each of
      two conserved threonines lining the monomeric urea pores reduced H2O and NH3
      permeability. Our data confirm that UT-B has significant H2O permeability and for
      the first time demonstrate significant NH3 permeability. Thus the UTs become the
      third family of gas channels. Inhibitor and mutagenesis studies and results of MD
      simulations suggest that NH3 and H2O pass through the three monomeric urea
      channels in UT-B.

PMID- 23552863
TI  - Overexpression of catalase prevents hypertension and tubulointerstitial fibrosis
      and normalization of renal angiotensin-converting enzyme-2 expression in Akita
      mice.
AB  - We investigated the relationship among oxidative stress, hypertension, renal
      injury, and angiotensin-converting enzyme-2 (ACE2) expression in type 1 diabetic
      Akita mice. Blood glucose, blood pressure, and albuminuria were monitored for up
      to 5 mo in adult male Akita and Akita catalase (Cat) transgenic (Tg) mice
      specifically overexpressing Cat, a key antioxidant enzyme in their renal proximal
      tubular cells (RPTCs). Same-age non-Akita littermates and Cat-Tg mice served as
      controls. In separate studies, adult male Akita mice (14 wk) were treated with
      ANG 1-7 (500 MUg.kg-1.day-1 sc) +/- A-779, an antagonist of the Mas receptor (10
      mg.kg-1.day-1 sc), and euthanized at the age of 18 wk. The left kidneys were
      processed for histology and apoptosis studies. Renal proximal tubules were
      isolated from the right kidneys to assess protein and gene expression. Urinary
      angiotensinogen (AGT), angiotensin II (ANG II), and ANG 1-7 were quantified by
      specific ELISAs. Overexpression of Cat attenuated renal oxidative stress;
      prevented hypertension; normalized RPTC ACE2 expression and urinary ANG 1-7
      levels (both were low in Akita mice); ameliorated glomerular filtration rate,
      albuminuria, kidney hypertrophy, tubulointerstitial fibrosis, and tubular
      apoptosis; and suppressed profibrotic and proapoptotic gene expression in RPTCs
      of Akita Cat-Tg mice compared with Akita mice. Furthermore, daily administration
      of ANG 1-7 normalized systemic hypertension in Akita mice, which was reversed by
      A-779. These data demonstrate that Cat overexpression prevents hypertension and
      progression of nephropathy and highlight the importance of intrarenal oxidative
      stress and ACE2 expression contributing to hypertension and renal injury in
      diabetes.

PMID- 23552864
TI  - betaENaC is required for whole cell mechanically gated currents in renal vascular
      smooth muscle cells.
AB  - Myogenic constrictor responses in small renal arteries and afferent arterioles
      are suppressed in mice with reduced levels of beta-epithelial Na+ channel
      (betaENaC(m/m)). The underlying mechanism is unclear. Decreased activity of
      voltage-gated calcium channels (VGCC) or mechanically gated ion channels and
      increased activity of large conductance calcium-activated potassium (BK) channels
      are a few possible mechanisms. The purpose of this study was to determine if
      VGCC, BK, or mechanically gated ion channel activity was altered in renal
      vascular smooth muscle cell (VSMC) from betaENaC(m/m) mice. To address this, we
      used whole cell patch-clamp electrophysiological approaches in freshly isolated
      renal VSMCs. Compared with betaENaC(+/+) controls, the current-voltage
      relationships for VGCC and BK activity are similar in betaENaC(m/m) mice. These
      findings suggest neither VGCC nor BK channel dysfunction accounts for reduced
      myogenic constriction in betaENaC(m/m) mice. We then examined mechanically gated
      currents using a novel in vitro assay where VSMCs are mechanically activated by
      stretching an underlying elastomer. We found the mechanically gated currents,
      predominantly carried by Na+, are observed with less frequency (87 vs. 43%) and
      have smaller magnitude (-54.1 +/- 12.5 vs. -20.9 +/- 4.9 pA) in renal VSMCs from
      betaENaC(m/m) mice. Residual currents are expected in this model since VSMC
      betaENaC expression is reduced by 50%. These findings suggest betaENaC is
      required for normal mechanically gated currents in renal VSMCs and their
      disruption may account for the reduced myogenic constriction in the betaENaC(m/m)
      model. Our findings are consistent with the role of betaENaC as a VSMC
      mechanosensor and function of evolutionarily related nematode degenerin proteins.

PMID- 23552865
TI  - OPN deficiency results in severe glomerulosclerosis in uninephrectomized mice.
AB  - Osteopontin (OPN) expression has been reported to be elevated in experimental
      models of renal injury such as arterial hypertension or diabetic nephropathy
      finally leading to focal segmental glomerulosclerosis (FSGS). FSGS is
      characterized by glomerular matrix deposition and loss or damage of podocytes
      that represent the main constituents of the glomerular filtration barrier. To
      evaluate the role of OPN in the kidney we investigated WT and OPN knockout mice
      (OPN-/-) without treatment, after uninephrectomy (UNX), as well as after UNX and
      desoxycorticosterone acetate (DOCA)-salt treatment with respect to urine
      parameters, glomerular morphology, and expression of podocyte markers. OPN-/-
      mice showed normal urine parameters while a thickening of the glomerular basement
      membrane was evident. Intriguingly, following UNX, OPN-/- mice exhibited
      prominent FSGS, proteinuria, and glomerular matrix deposition. Electron
      microscopy revealed bulgings of the glomerular basement membrane and occasionally
      an effacement of podocytes. After UNX and DOCA-salt treatment, severe glomerular
      lesions as well as proteinuria and albuminuria were seen in WT and OPN-/- mice.
      Moreover, we found a reduction of specific markers such as Wilm's tumor-1,
      podocin, and synaptopodin in both experimental groups indicating a loss of
      podocytes. Podocyte damage was accompanied by increased number of Ki-67-positive
      cells in the parietal epithelium of Bowman's capsule. We conclude that OPN plays
      a crucial role in adaptation of podocytes following renal ablation and is
      renoprotective when glomerular mechanical load is increased.

PMID- 23552866
TI  - Reduction of chronic rejection of renal allografts by anti-transforming growth
      factor-beta antibody therapy in a rat model.
AB  - There is no effective treatment for chronic rejection (CR) that largely limits
      long-term survival of kidney transplants. Transforming growth factor (TGF)-beta
      is a fibrogenic factor for tissue fibrosis. This study was to test the efficacy
      of an anti-TGF-beta antibody in preventing the CR of renal allografts in a
      preclinical model. Male Lewis rats (RT11) were orthotopically transplanted with
      donor kidneys from male Fischer 344 (RT11v1) rats and were treated with either
      anti-TGF-beta or a control antibody. The CR of renal allografts was assessed by
      semiquantitative histological analyses, and intragraft cytokines and fibrosis
      related genes ware examined by PCR arrays. Compared with the control antibody,
      anti-TGF-beta antibody treatment significantly reduced recipients' proteinuria (P
      = 0.0002), and CR in renal transplants, which was indicated by the fewer injured
      renal tubules, glomeruli, and interlobular arterioles or arteries, and by less
      mononuclear cell infiltration and interstitial fibrosis in the anti-TGF-beta
      antibody-treated group (P < 0.05), but not significantly attenuate the ratios of
      different infiltrating leukocytes. These pathological changes were associated
      with downregulation of TGF-beta1, TGF-beta2, and proinflammatory cytokines, or
      with upregulation of anti-fibrotic HGF, BMP5, and BMP7. The therapeutic effect of
      the anti-TGF-beta antibody was further confirmed by its prevention of graft
      dysfunction, indicated by lower levels of serum creatinine and blood urea
      nitrogen or higher creatinine clearance in anti-TGF-beta antibody-treated
      recipients compared with those in control recipients (P < 0.05). In conclusion,
      the anti-TGF-beta antibody (1D11) treatment significantly reduces CR of renal
      allografts in rats, suggesting the therapeutic potential of this antibody therapy
      for treating CR of kidney transplants in patients.

PMID- 23552867
TI  - Antihypertensive and renoprotective effect of the kinin pathway activated by
      potassium in a model of salt sensitivity following overload proteinuria.
AB  - The albumin overload model induces proteinuria and tubulointersitial damage,
      followed by hypertension when rats are exposed to a hypersodic diet. To
      understand the effect of kinin system stimulation on salt-sensitive hypertension
      and to explore its potential renoprotective effects, the model was induced in
      Sprague-Dawley rats that had previously received a high-potassium diet to enhance
      activity of the kinin pathway, followed with/without administration of icatibant
      to block the kinin B2 receptor (B2R). A disease control group received albumin
      but not potassium or icatibant, and all groups were exposed to a hypersodic diet
      to induce salt-sensitive hypertension. Potassium treatment increased the
      synthesis and excretion of tissue kallikrein (Klk1/rKLK1) accompanied by a
      significant reduction in blood pressure and renal fibrosis and with
      downregulation of renal transforming growth factor-beta (TGF-beta) mRNA and
      protein compared with rats that did not receive potassium. Participation of the
      B2R was evidenced by the fact that all beneficial effects were lost in the
      presence of the B2R antagonist. In vitro experiments using the HK-2 proximal
      tubule cell line showed that treatment of tubular cells with 10 nM bradykinin
      reduced the epithelial-mesenchymal transdifferentiation and albumin-induced
      production of TGF-beta, and the effects produced by bradykinin were prevented by
      pretreatment with the B2R antagonist. These experiments support not only the
      pathogenic role of the kinin pathway in salt sensitivity but also sustain its
      role as a renoprotective, antifibrotic paracrine system that modulates renal
      levels of TGF-beta.

PMID- 23552868
TI  - Performance and utilization of an emergency department electronic screening tool
      for pneumonia.

PMID- 23552869
TI  - Protein tyrosine phosphatase kappa (PTPRK) is a negative regulator of adhesion
      and invasion of breast cancer cells, and associates with poor prognosis of breast
      cancer.
AB  - PURPOSE: Receptor-like protein tyrosine phosphatase kappa (PTPRK) has been shown
      to exhibit homophilic binding. It is a putative tumour suppressor in primary
      central nervous system lymphomas and colorectal cancer. The present study
      investigated the expression of PTPRK in breast cancer and the biological impact
      of PTPRK on breast cancer cells. METHODS: Expression of PTPRK protein and gene
      transcript was examined in a cohort of breast cancer patients. The association of
      PTPRK transcript level and pathological and clinical aspects was then analysed.
      Knockdown of PTPRK in breast cancer cells was performed using a specific anti
      PTPRK transgene. The impact of PTPRK knockdown on breast cancer cells was
      investigated using in vitro cell function assays. RESULTS: Lower levels of PTPRK
      transcripts were seen in the advanced breast cancer. The reduced PTPRK transcript
      levels were associated with poor prognosis of the disease. PTPRK transcript
      levels were decreased in the primary tumours of patients who died from breast
      cancer or had metastases. Patients with lower expression of PTPRK had shorter
      survival compared with those higher expression levels of PTPRK. Knockdown of
      PTPRK resulted in increased proliferation, adhesion, invasion, and migration of
      breast cancer cells in vitro. CONCLUSIONS: Decreased expression of PTPRK in
      breast cancer is correlated with poor prognosis. PTPRK is a negative regulator of
      adhesion, invasion, migration, and proliferation of breast cancer cells. This
      suggests that PTPRK is a potential tumour suppressor in breast cancer.

PMID- 23552870
TI  - Optical techniques for the noninvasive diagnosis of skin cancer.
AB  - PURPOSE: The aim of this paper is to provide an overview of the most investigated
      optical diagnostic techniques: optical coherence tomography, fluorescence
      spectrometry, reflectance spectrometry, Raman spectroscopy, and confocal
      microscopy. METHODS: A search of three databases was conducted using specific
      keywords and explicit inclusion and exclusion criteria for the analysis of the
      performances of these techniques in the pre- and postoperative diagnosis of skin
      cancers. RESULTS: Optical coherence tomography has shown promising results in the
      assessment of deep margins of skin tumors and inflammatory skin diseases, but
      differentiating premalignant from malignant lesions proved to be less effective.
      Fluorescence spectroscopy proved to be effective in revealing the biochemical
      composition of tissue; early detection of malignant melanoma was reliable only
      with stepwise two-photon excitation of melanin, while tumoral margin assessment
      and differential diagnosis between malignant and non-malignant lesions showed
      some conflicting results. Characterization of the structural properties of tissue
      can be made using diffuse reflectance spectrometry, and the values of the
      specificity and sensitivity of this method are ranging between 72-92 % and 64-92
      %, respectively. Raman spectroscopy proved to have better results both in
      carcinoma and melanoma diagnosis with sensitivities and specificities above 90 %
      and high above 50 %, respectively. Confocal microscopy is the closest technique
      to pathological examination and has gained the most clinical acceptance, despite
      the need for a standardization of the interpretation algorithm. CONCLUSIONS: In
      conclusion, these optical techniques proved to be effective in the diagnosis of
      skin cancer, but further studies are needed in finding the appropriate method or
      combination of methods that can have wide clinical applications.

PMID- 23552871
TI  - High circulating VEGF level predicts poor overall survival in lung cancer.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is considered as the best
      validated key regulator of angiogenesis, while the prognostic role of circulating
      VEGF in lung cancer remains controversial. We conducted a meta-analysis to
      evaluate the prognostic role of circulating VEGF. METHODS: Nineteen studies with
      a total number of 2,890 patients were analyzed in our meta-analysis. Hazard
      ratios (HRs) and their 95 % confidence intervals (CIs) were used to quantify the
      predictive ability of circulating VEGF on survival. RESULTS: The pooled HR of all
      17 studies evaluating overall survival (OS) was 1.29 (95 % CI 1.19-1.40, p <
      0.001), indicating high circulating VEGF predicted poor OS. When grouped by
      disease stages, the pooled HRs were 0.97 (95 % CI 0.47-1.47, p < 0.001) for
      operable stage and 1.34 (95 % CI 1.18-1.49, p < 0.001) for inoperable stage. The
      pooled HRs were 1.28 (95 % CI 1.15-1.42, p < 0.001) for serum and 1.31 (95 % CI
      1.13-1.49, p < 0.001) for plasma, when categorized by blood sample. Meta-analysis
      of circulating VEGF related to progression-free survival (PFS) was performed in 7
      studies, and the pooled HR was 1.03 (95 % CI 0.96-1.09). CONCLUSIONS: Our results
      indicate that high level of circulating VEGF predicts poor OS in lung cancer, yet
      it does not predict poor PFS.

PMID- 23552872
TI  - Radical radiotherapy in high-risk prostate cancer patients with high or ultra
      high initial PSA levels: a single institution analysis.
AB  - PURPOSE: Purpose of this study is to analyze outcomes and pre-treatment
      prognostic factors in high-risk prostate cancer patients with initial PSA >= 20
      ng/mL, treated with high-dose external beam radiotherapy (EBRT) and androgen
      deprivation therapy (ADT) in a single institution. METHODS: Between March 2003
      and December 2011, 155 consecutive high-risk prostate cancer patients (a)
      presenting with pre-treatment PSA level >= 20 ng/mL, (b) treated with definitive
      EBRT, and (c) with a minimum follow-up of 24 months were included in this
      retrospective analysis. Phoenix definition was used to define biochemical
      control. Primary endpoints were as follows: biochemical disease-free survival
      (bDFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS)
      and overall survival (OS). Multivariate analysis was performed to determine the
      independent prognostic impact of pre-treatment clinical factors [T stage, PSA,
      and Gleason score (GS)]. RESULTS: At a median follow-up time of 62 months,
      actuarial bDFS, DMFS, CSS, and OS at 5 years were 64.8, 85.2, 95.8, and 94.4 %,
      respectively. On multivariate analysis, only GS was significantly associated with
      three clinical endpoints (bDFS: HR 1.6; p = 0.022, CSS: HR 4.27, p = 0.044, OS:
      HR 2.6; p = 0.038). Pre-treatment zenith PSA was associated only with bDFS (HR
      1.87; p = 0.027). CONCLUSIONS: Patients with "high" PSA levels (>= 20 ng/mL)
      showed favorable clinical outcomes, supporting the role of local radiotherapy as
      primary therapy in combination with long-term ADT in patients with high PSA
      levels at diagnosis. A GS of 8-10 is the strongest predictor of outcome.

PMID- 23552873
TI  - Persistence with bisphosphonates in patients with metastatic breast cancer: a
      retrospective database analysis.
AB  - BACKGROUND: In women with breast cancer and bone metastasis, compliance to
      antiresorptive treatment is of upmost importance to ensure maximum effectiveness
      in clinical practice. The aim of our study was to investigate persistence with
      oral and intravenous bisphosphonates (BIS) in a large group of women with
      metastatic breast cancer and to identify the determinants of non-persistence.
      PATIENTS AND METHODS: We used data from the Disease Analyzer database (IMS
      Health, Germany), which includes 2,067 general practices and 397 gynaecological
      practices. From a dataset of 20 million patients, we identified 1,045 patients
      diagnosed between January 2001 and December 2010 with bone metastasis (ICD 10:
      C795) following breast cancer (ICD 10: C50) with first-time cancer-related
      bisphosphonate prescriptions (ATC: M03B4). Of these, 763 patients received
      intravenous treatment, and 280 patients received oral BIS treatment. RESULTS:
      After 1 year, 35.3 % of patients treated with intravenous, and 45.6 % of patients
      treated with oral bisphosphonates discontinued their therapy (p = 0.002).
      Multivariate Cox Regression analyses showed a significant increased risk of
      treatment discontinuation in patients using intravenous BIS (HR: 0.82) compared
      with oral BIS. Patients younger than 50 (HR: 1.52) were most likely to
      discontinue treatment compared with the reference group of women over 70. The use
      of other treatments, such as chemotherapy or hormone therapy, was associated with
      a decreased risk of treatment discontinuation. Moreover, treatment
      discontinuation was higher in West Germany compared with East Germany (HR: 1.65)
      and in patients covered under private health insurance (HR: 1.33). CONCLUSIONS:
      Persistence with all bisphosphonate treatments in women with breast cancer and
      bone metastasis is low and needs to be significantly increased to improved
      outcomes in clinical practice. Further research is required to understand this
      complex issue.

PMID- 23552874
TI  - Space-confined fabrication of silver nanodendrites and their enhanced SERS
      activity.
AB  - Here we report a controllable method based on electrodeposition to fabricate Ag
      nanodendrites (NDs) on a microwell patterned electrode. The microwell patterns on
      the ITO electrode are fabricated via the microcontact printing technique. By
      varying the microwell size and electrodeposition time, the morphology of metal
      deposits on the microwell patterned ITO electrode can be tuned from boulders to
      dendrites. At the edge of the microwells, the current density was strengthened,
      which incurs rapid nucleation. The nucleus develops into dendrites because of
      Mullins-Sekerka instability. However, only boulders were observed at the center
      of microwells. By reducing the size of the microwells, only NDs were fabricated
      due to the edge effect. On the basis of understanding the underlying mechanism
      for dendritic growth in a confined space, our method is used for fabricating
      other noble metal (Au, Pt) nanodendrites. The controllable synthesis of Au and Pt
      NDs indicates the universality of this method. Compared with Ag film obtained
      from electron beam evaporation, the as-prepared Ag NDs exhibit highly enhanced
      surface-enhanced Raman scattering (SERS) sensitivity when they are used to detect
      rhodamine 6G (R6G). This approach provides a very controllable, reliable and
      general way for space-confined fabricating the noble metal nanodendrite arrays
      which show great promise in catalysis, sensing, biomedicine, electronic and
      magnetic devices.

PMID- 23552875
TI  - ACP Journal Club. PCI using drug-eluting stents had higher mortality than CABG in
      diabetes and multivessel CAD.

PMID- 23552877
TI  - Potential chemopreventive activity of a new macrolide antibiotic from a marine
      derived Micromonospora sp.
AB  - Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are
      known to have the potential of mediating cancer chemopreventive activity. As part
      of a program to discover novel phase II enzyme-inducing molecules, we identified
      a marine-derived actinomycete strain (CNJ-878) that exhibited activity with
      cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C
      (1), as well as 5-O-alpha-L-rhamnosyltylactone (2), were isolated from the
      culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and
      glutathione levels by two-fold with CD values of 10.1 and 27.7 MUM, respectively.
      In addition, glutathione reductase and glutathione peroxidase activities were
      elevated. This is the first reported member of the macrolide class of antibiotics
      found to mediate these responses.

PMID- 23552879
TI  - Unilateral hyperpigmented lesion of the breast in a young woman. Melanosis of the
      areola and nipple.

PMID- 23552878
TI  - Cytotoxic and antibacterial cembranoids from a South China Sea soft coral,
      Lobophytum sp.
AB  - Chemical examination of a South China Sea soft coral Lobophytum sp. led to the
      isolation of three new alpha-methylene-gamma-lactone-containing cembranoids,
      (1R*,3R*, 4R*,14R*,7E,11E)-3,4-epoxycembra-7,11,15(17)-trien-16,14-olide (1),
      (1R*,7S*,14S*,3E, 11E)-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide
      (2), and (1R*,7S*,14S*, 3E,11E)-18-acetoxy-7-hydroperoxycembra-3,8(19),11,15(17)
      tetraen-16,14-olide (3), along with eleven known analogues 4-14. The structures
      of the new compounds were elucidated through extensive spectroscopic analysis,
      including 1D and 2D NMR data. Compounds 1-3 exhibited moderate cytotoxic activity
      against the selected tumor cell lines. Moreover, 2 and 3 were found to be
      moderate inhibitors against the bacteria S. aureus and S. pneumoniae.

PMID- 23552880
TI  - Detection of temperature distribution via recovering electrical conductivity in
      MREIT.
AB  - In radiofrequency (RF) ablation or hyperthermia, internal temperature
      measurements and tissue property imaging are important to control their outputs
      and assess the treatment effect. Recently, magnetic resonance electrical
      impedance tomography (MREIT), as a non-invasive imaging method of internal
      conductivity distribution using an MR scanner, has been developed. Its
      reconstruction algorithm uses measured magnetic flux density induced by injected
      currents. The MREIT technique has the potential to visualize electrical
      conductivity of tissue with high spatial resolution and measure relative
      conductivity variation according to the internal temperature change based on the
      fact that the electrical conductivity of biological tissues is sensitive to the
      internal temperature distribution. In this paper, we propose a method to provide
      a non-invasive alternative to monitor the internal temperature distribution by
      recovering the electrical conductivity distribution using the MREIT technique. To
      validate the proposed method, we design a phantom with saline solution and a thin
      transparency film in a form of a hollow cylinder with holes to create anomalies
      with different electrical and thermal conductivities controlled by morphological
      structure. We first prove the temperature maps with respect to spatial and time
      resolution by solving the thermal conductivity partial differential equation with
      the real phantom experimental environment. The measured magnetic flux density and
      the reconstructed conductivity distributions using the phantom experiments were
      compared to the simulated temperature distribution. The relative temperature
      variation of two testing objects with respect to the background saline was
      determined by the relative conductivity contrast ratio (rCCR,%). The relation
      between the temperature and conductivity measurements using MREIT was
      approximately linear with better accuracy than 0.22  degrees C.

PMID- 23552881
TI  - Metal-enhanced fluorescence in the life sciences: here, now and beyond.
AB  - We discuss the phenomenon of enhanced fluorescence in the proximity of metal
      nanostructures addressing the question of how much fluorescence signal can be
      obtained from fluorophores in such altered environments. We review its
      applicability for the methodologies used in the life science, such as
      immunoassays, flow cytometry and bioimaging. Experimental and theoretical
      scenarios employing various metal nanostructures - such as homogeneous enhancing
      substrates, fluorescence-enhancing microbeads, and metal core-dielectric shell
      nanocomposites - are described. 

PMID- 23552882
TI  - A mechanism of resistance to gefitinib mediated by cellular reprogramming and the
      acquisition of an FGF2-FGFR1 autocrine growth loop.
AB  - Despite initial and often dramatic responses of epidermal growth factor receptor
      (EGFR)-addicted lung tumors to the EGFR-specific tyrosine kinase inhibitors
      (TKIs), gefitinib and erlotinib, nearly all develop resistance and relapse. To
      explore novel mechanisms mediating acquired resistance, we employed non-small
      cell lung cancer (NSCLC) cell lines bearing activating mutations in EGFR and
      rendered them resistant to EGFR-specific TKIs through chronic adaptation in
      tissue culture. In addition to previously observed resistance mechanisms
      including EGFR-T790M 'gate-keeper' mutations and MET amplification, a subset of
      the seven chronically adapted NSCLC cell lines including HCC4006, HCC2279 and
      H1650 cells exhibited marked induction of fibroblast growth factor (FGF) 2 and
      FGF receptor 1 (FGFR1) mRNA and protein. Also, adaptation to EGFR-specific TKIs
      was accompanied by an epithelial to mesenchymal transition (EMT) as assessed by
      changes in CDH1, VIM, ZEB1 and ZEB2 expression and altered growth properties in
      Matrigel. In adapted cell lines exhibiting increased FGF2 and FGFR1 expression,
      measures of growth and signaling, but not EMT, were blocked by FGFR-specific
      TKIs, an FGF-ligand trap and FGFR1 silencing with RNAi. In parental HCC4006
      cells, cell growth was strongly inhibited by gefitinib, although drug-resistant
      clones progress within 10 days. Combined treatment with gefitinib and AZD4547, an
      FGFR-specific TKI, prevented the outgrowth of drug-resistant clones. Thus,
      induction of FGF2 and FGFR1 following chronic adaptation to EGFR-specific TKIs
      provides a novel autocrine receptor tyrosine kinase-driven bypass pathway in a
      subset of lung cancer cell lines that are initially sensitive to EGFR-specific
      TKIs. The findings support FGFR-specific TKIs as potentially valuable additions
      to existing targeted therapeutic strategies with EGFR-specific TKIs to prevent or
      delay acquired resistance in EGFR-driven NSCLC.

PMID- 23552883
TI  - Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells
      through increase of receptor tyrosine kinase MET.
AB  - Ovarian cancer is one of the most aggressive female reproductive tract tumors.
      Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However,
      ovarian cancers often acquire chemotherapeutic resistance to this agent. We
      investigated the mechanism of chemoresistance by analysis of microRNAs using the
      ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We
      found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of
      miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to
      bind to the 3'-UTR of mRNA of MET, and the decrease in MET correlated to higher
      sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET
      inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In
      addition, lower levels of miR31 and higher expression of MET in human ovarian
      cancer specimens were significantly correlated with PTX chemoresistance and poor
      prognosis. This study demonstrated miR31-dependent regulation of MET for
      chemoresistance of ovarian cancer, raising the possibility that combination
      therapy with a MET inhibitor and PTX will increase PTX efficacy.

PMID- 23552884
TI  - Probing carbohydrate-carbohydrate interactions by photoswitchable supramolecular
      glycoclusters.
AB  - The synthesis of photo-switchable glycoclusters with distinct sugar arrangements
      is described and the use of these clusters to study carbohydrate-carbohydrate
      interactions (CCIs) is demonstrated.

PMID- 23552885
TI  - A call to action: improving value by emphasizing patient-centered care at the end
      of life.

PMID- 23552886
TI  - Why do nonwhite patients undergo amputation more commonly than white patients?

PMID- 23552887
TI  - Potential protective effect of sunitinib after administration of diclofenac:
      biochemical and histopathological drug-drug interaction assessment in a mouse
      model.
AB  - Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell
      carcinoma. Diclofenac is used in cancer pain management. Coadministration may
      mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT,
      AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart,
      brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline
      (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80,
      100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and
      sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min
      before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers
      and tissue histopathology were assessed. AST was 92.2 +/- 8.0 U/L in group A and
      159.7 +/- 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1
      152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 +/-
      1.6 U/L (group A), 95.1 +/- 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in
      group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function
      biomarker BUN was 16.3 +/- 0.6 mg/dl (group A) and increased to 29.9 +/- 2.6
      mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and
      26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in
      group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4
      pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological
      assessment (vascular and inflammation damages) showed toxicity in group B (p <
      0.05) and mild toxicity in group C. Damage was significantly lesser in group D
      than group B (p < 0.05). Spleen only showed toxicity after coadministration.
      These results suggest vascular and inflammation protective effects of sunitinib,
      not shown after biomarker analysis.

PMID- 23552889
TI  - Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive
      cocaine seeking.
AB  - Loss of control over harmful drug seeking is one of the most intractable aspects
      of addiction, as human substance abusers continue to pursue drugs despite
      incurring significant negative consequences. Human studies have suggested that
      deficits in prefrontal cortical function and consequential loss of inhibitory
      control could be crucial in promoting compulsive drug use. However, it remains
      unknown whether chronic drug use compromises cortical activity and, equally
      important, whether this deficit promotes compulsive cocaine seeking. Here we use
      a rat model of compulsive drug seeking in which cocaine seeking persists in a
      subgroup of rats despite delivery of noxious foot shocks. We show that prolonged
      cocaine self-administration decreases ex vivo intrinsic excitability of deep
      layer pyramidal neurons in the prelimbic cortex, which was significantly more
      pronounced in compulsive drug-seeking animals. Furthermore, compensating for
      hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex
      stimulation significantly prevented compulsive cocaine seeking, whereas
      optogenetic prelimbic cortex inhibition significantly increased compulsive
      cocaine seeking. Our results show a marked reduction in prelimbic cortex
      excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic
      prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus,
      targeted stimulation of the prefrontal cortex could serve as a promising therapy
      for treating compulsive drug use.

PMID- 23552891
TI  - Diverse type VI secretion phospholipases are functionally plastic antibacterial
      effectors.
AB  - Membranes allow the compartmentalization of biochemical processes and are
      therefore fundamental to life. The conservation of the cellular membrane,
      combined with its accessibility to secreted proteins, has made it a common target
      of factors mediating antagonistic interactions between diverse organisms. Here we
      report the discovery of a diverse superfamily of bacterial phospholipase enzymes.
      Within this superfamily, we defined enzymes with phospholipase A1 and A2
      activity, which are common in host-cell-targeting bacterial toxins and the venoms
      of certain insects and reptiles. However, we find that the fundamental role of
      the superfamily is to mediate antagonistic bacterial interactions as effectors of
      the type VI secretion system (T6SS) translocation apparatus; accordingly, we name
      these proteins type VI lipase effectors. Our analyses indicate that PldA of
      Pseudomonas aeruginosa, a eukaryotic-like phospholipase D, is a member of the
      type VI lipase effector superfamily and the founding substrate of the haemolysin
      co-regulated protein secretion island II T6SS (H2-T6SS). Although previous
      studies have specifically implicated PldA and the H2-T6SS in pathogenesis, we
      uncovered a specific role for the effector and its secretory machinery in intra-
      and interspecies bacterial interactions. Furthermore, we find that this effector
      achieves its antibacterial activity by degrading phosphatidylethanolamine, the
      major component of bacterial membranes. The surprising finding that virulence
      associated phospholipases can serve as specific antibacterial effectors suggests
      that interbacterial interactions are a relevant factor driving the continuing
      evolution of pathogenesis.

PMID- 23552893
TI  - Terrestrial water fluxes dominated by transpiration.
AB  - Renewable fresh water over continents has input from precipitation and losses to
      the atmosphere through evaporation and transpiration. Global-scale estimates of
      transpiration from climate models are poorly constrained owing to large
      uncertainties in stomatal conductance and the lack of catchment-scale
      measurements required for model calibration, resulting in a range of predictions
      spanning 20 to 65 per cent of total terrestrial evapotranspiration (14,000 to
      41,000 km(3) per year) (refs 1, 2, 3, 4, 5). Here we use the distinct isotope
      effects of transpiration and evaporation to show that transpiration is by far the
      largest water flux from Earth's continents, representing 80 to 90 per cent of
      terrestrial evapotranspiration. On the basis of our analysis of a global data set
      of large lakes and rivers, we conclude that transpiration recycles 62,000 +/-
      8,000 km(3) of water per year to the atmosphere, using half of all solar energy
      absorbed by land surfaces in the process. We also calculate CO2 uptake by
      terrestrial vegetation by connecting transpiration losses to carbon assimilation
      using water-use efficiency ratios of plants, and show the global gross primary
      productivity to be 129 +/- 32 gigatonnes of carbon per year, which agrees, within
      the uncertainty, with previous estimates. The dominance of transpiration water
      fluxes in continental evapotranspiration suggests that, from the point of view of
      water resource forecasting, climate model development should prioritize
      improvements in simulations of biological fluxes rather than physical
      (evaporation) fluxes.

PMID- 23552894
TI  - HIV: Roadmaps to a vaccine.

PMID- 23552896
TI  - Diverse and heritable lineage imprinting of early haematopoietic progenitors.
AB  - Haematopoietic stem cells (HSCs) and their subsequent progenitors produce blood
      cells, but the precise nature and kinetics of this production is a contentious
      issue. In one model, lymphoid and myeloid production branch after the lymphoid
      primed multipotent progenitor (LMPP), with both branches subsequently producing
      dendritic cells. However, this model is based mainly on in vitro clonal assays
      and population-based tracking in vivo, which could miss in vivo single-cell
      complexity. Here we avoid these issues by using a new quantitative version of
      'cellular barcoding' to trace the in vivo fate of hundreds of LMPPs and HSCs at
      the single-cell level. These data demonstrate that LMPPs are highly heterogeneous
      in the cell types that they produce, separating into combinations of lymphoid-,
      myeloid- and dendritic-cell-biased producers. Conversely, although we observe a
      known lineage bias of some HSCs, most cellular output is derived from a small
      number of HSCs that each generates all cell types. Crucially, in vivo analysis of
      the output of sibling cells derived from single LMPPs shows that they often share
      a similar fate, suggesting that the fate of these progenitors was imprinted.
      Furthermore, as this imprinting is also observed for dendritic-cell-biased LMPPs,
      dendritic cells may be considered a distinct lineage on the basis of separate
      ancestry. These data suggest a 'graded commitment' model of haematopoiesis, in
      which heritable and diverse lineage imprinting occurs earlier than previously
      thought.

PMID- 23552897
TI  - Structural biology: a solution to the telomerase puzzle.

PMID- 23552898
TI  - Phymatous transformation of facial cutaneous vascular malformations: clues to
      phyma pathogenesis.

PMID- 23552895
TI  - The architecture of Tetrahymena telomerase holoenzyme.
AB  - Telomerase adds telomeric repeats to chromosome ends using an internal RNA
      template and a specialized telomerase reverse transcriptase (TERT), thereby
      maintaining genome integrity. Little is known about the physical relationships
      among protein and RNA subunits within a biologically functional holoenzyme. Here
      we describe the architecture of Tetrahymena thermophila telomerase holoenzyme
      determined by electron microscopy. Six of the seven proteins and the TERT-binding
      regions of telomerase RNA (TER) have been localized by affinity labelling.
      Fitting with high-resolution structures reveals the organization of TERT, TER and
      p65 in the ribonucleoprotein (RNP) catalytic core. p50 has an unanticipated role
      as a hub between the RNP catalytic core, p75-p19-p45 subcomplex, and the DNA
      binding Teb1. A complete in vitro holoenzyme reconstitution assigns function to
      these interactions in processive telomeric repeat synthesis. These studies
      provide the first view of the extensive network of subunit associations necessary
      for telomerase holoenzyme assembly and physiological function.

PMID- 23552900
TI  - ACP Journal Club. Review: continuous glucose monitoring reduces HbA1c more than
      self-monitoring in type 1 diabetes.

PMID- 23552899
TI  - High responsivity, fast ultraviolet photodetector fabricated from ZnO
      nanoparticle-graphene core-shell structures.
AB  - We report a simple, efficient and versatile method for assembling metal oxide
      nanomaterial-graphene core-shell structures. An ultraviolet photodetector
      fabricated from the ZnO nanoparticle-graphene core-shell structures showed high
      responsivity and fast transient response, which are attributed to the improved
      carrier transport efficiency arising from graphene encapsulation.

PMID- 23552890
TI  - Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
AB  - Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific
      neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in
      approximately 20% of HIV-1-infected individuals, and details of their generation
      could provide a blueprint for effective vaccination. Here we report the
      isolation, evolution and structure of a broadly neutralizing antibody from an
      African donor followed from the time of infection. The mature antibody, CH103,
      neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure
      with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4
      binding-site recognition. Virus and antibody gene sequencing revealed concomitant
      virus evolution and antibody maturation. Notably, the unmutated common ancestor
      of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope
      glycoprotein, and evolution of antibody neutralization breadth was preceded by
      extensive viral diversification in and near the CH103 epitope. These data
      determine the viral and antibody evolution leading to induction of a lineage of
      HIV-1 broadly neutralizing antibodies, and provide insights into strategies to
      elicit similar antibodies by vaccination.

PMID- 23552901
TI  - Impact of aging on the clinical outcomes of Japanese patients with coronary
      artery disease after percutaneous coronary intervention.
AB  - Japan has become an aging society, resulting in an increased prevalence of
      coronary artery disease. However, clinical outcomes of elderly Japanese patients
      after percutaneous coronary intervention (PCI) remain unclear. Of the 15,227
      patients in the Shinken Database, a single-hospital-based cohort of new patients,
      1,214 patients who underwent PCI, was evaluated to determine the differences in
      clinical outcomes between the elderly (>=75 years) (n = 260) and the non-elderly
      (<75 years) (n = 954) patients. A major adverse cardiac event (MACE) was defined
      as a composite end point, including all-cause death, myocardial infarction (MI),
      and target lesion revascularization. Male gender and obesity were less common,
      and the estimated glomerular filtration rate (eGFR) was significantly lower in
      the elderly than in the non-elderly. Left ventricular ejection fraction (LVEF)
      was comparable between these groups. Left main trunk disease and multivessel
      disease were more common in the elderly than in the non-elderly group. Occurrence
      of MACE was frequent, and the incidences of all-cause death, cardiac death, and
      the admission rate for heart failure were significantly higher in the elderly
      patients. Multivariate analysis showed that prior MI, low eGFR, and poor LVEF
      were independent predictors for all-cause death in the elderly patients. Elderly
      patients had worse clinical outcomes than the non-elderly patients. Low eGFR and
      LVEF were independent predictors of all-cause death after PCI, suggesting that
      left ventricular dysfunction and renal dysfunction might synergistically
      contribute to the adverse clinical outcomes of the elderly patients undergoing
      PCI. 

PMID- 23552902
TI  - Higher serum uric acid and lipoprotein(a) are correlated with coronary spasm.
AB  - It has been reported that a major cause of coronary vasospastic angina (VSA) is
      endothelial dysfunction of the coronary artery. On the other hand, some studies
      showed that serum uric acid and lipoprotein(a) are correlated with endothelial
      dysfunction. Thus, we examined whether uric acid and lipoprotein(a), are
      correlated with VSA. Four hundred forty-one patients with suspected VSA who
      underwent a coronary angiogram with acetylcholine provocation (ACh test) during
      an 8-year period were enrolled. We divided them into a VSA group, who showed
      coronary spasm by the ACh test, and an atypical chest pain (ACP) group, who
      showed negative ACh test. We compared serum markers between the two groups,
      including low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a),
      fibrinogen, total plasminogen activator inhibitor-1, and uric acid. Uric acid, hs
      CRP, and lipoprotein(a) were significantly higher in the VSA group than in the
      ACP group (all P < 0.05) while there were no significant differences in the other
      parameters. Multivariate analyses identified uric acid and lipoprotein(a) as
      significant independent markers for VSA. Uric acid and lipoprotein(a) are
      correlated with VSA, and medical intervention to decrease uric acid and
      lipoprotein(a) might be effective in controlling VSA. 

PMID- 23552903
TI  - On a dark-field signal generated by micrometer-sized calcifications in phase
      contrast mammography.
AB  - We show that a distribution of micrometer-sized calcifications in the human
      breast which are not visible in clinical x-ray mammography at diagnostic dose
      levels can produce a significant dark-field signal in a grating-based x-ray phase
      contrast imaging setup with a tungsten anode x-ray tube operated at 40 kVp. A
      breast specimen with invasive ductal carcinoma was investigated immediately after
      surgery by Talbot-Lau x-ray interferometry with a design energy of 25 keV. The
      sample contained two tumors which were visible in ultrasound and contrast-agent
      enhanced MRI but invisible in clinical x-ray mammography, in specimen radiography
      and in the attenuation images obtained with the Talbot-Lau interferometer. One of
      the tumors produced significant dark-field contrast with an exposure of 0.85 mGy
      air-kerma. Staining of histological slices revealed sparsely distributed grains
      of calcium phosphate with sizes varying between 1 and 40 MUm in the region of
      this tumor. By combining the histological investigations with an x-ray wave-field
      simulation we demonstrate that a corresponding distribution of grains of calcium
      phosphate in the form of hydroxylapatite has the ability to produce a dark-field
      signal which would-to a substantial degree-explain the measured dark-field image.
      Thus we have found the appearance of new information (compared to attenuation and
      differential phase images) in the dark-field image. The second tumor in the same
      sample did not contain a significant fraction of these very fine calcification
      grains and was invisible in the dark-field image. We conclude that some tumors
      which are invisible in x-ray absorption mammography might be detected in the x
      ray dark-field image at tolerable dose levels.

PMID- 23552904
TI  - Synthesis of peptoid based small molecular gelators by a multiple component
      reaction.
AB  - We report the synthesis and self-assembling properties of a new class of
      tripeptoids synthesized by a one-pot Ugi reaction from simple starting materials.
      Among the focused library of tripeptoids synthesized, several efficient low
      molecular weight gelators were obtained for aqueous DMSO and ethanol mixtures.

PMID- 23552905
TI  - Volatile and amino acid profiling of dry cured hams from different swine breeds
      and processing methods.
AB  - The flavor of dry cured ham explains the high appreciation of this product and it
      determines consumer acceptance. Volatile compounds provide valuable information
      about the odor and sensory quality of dry cured hams. Since amino acids are the
      origin of some volatile compounds of dry cured ham, the volatile and amino acid
      compositions of forty-one dry cured hams from Spain and France were determined to
      establish associations between them. The samples included different pig breeds
      (non Iberian vs. Iberian), which were additionally affected by different
      maturation times and feeding types (acorn vs. fodder). Results showed that 20
      volatile compounds were able to distinguish Iberian and non Iberian hams, and 16
      of those had relevant sensory impact according to their odor activity values. 3
      Methylbutanol, 2-heptanol and hexanal were among the most concentrated volatile
      compounds. In the case of non-volatile compounds, the concentrations of amino
      acids were generally higher in Iberian hams, and all the amino acids were able to
      distinguish Iberian from non Iberian hams with the exception of tryptophan and
      asparagine. A strong correlation of some amino acids with volatile compounds was
      found in the particular case of alcohols and aldehydes when only Iberian hams
      were considered. The high correlation values found in some cases proved that
      proteolysis plays an important role in aroma generation.

PMID- 23552906
TI  - Synthesis and biological evaluation of unsymmetrical curcumin analogues as
      tyrosinase inhibitors.
AB  - Synthesis and biological evaluation of unsymmetrical curcumin analogues (UCAs)
      have been achieved. Tyrosinase inhibitory activities were found for most of the
      prepared synthetic UCAs. Among them, compounds containing 4-hydroxyl-substituted
      phenolic rings with C-2/C-4- or C-3/C-4-dihydroxyl-substituted diphenolic rings
      were more active (IC(50) = 1.74~16.74 MUM) than 4-butylresorcinol and kojic acid,
      which suggested that the 4-hydroxyl groups in UCAs play a crucial role in
      tyrosinase inhibitory activities. The inhibition kinetics analyzed by Lineweaver
      Burk plots revealed compounds 3c and 3i containing catecholic rings were mixed
      competitive inhibitors, whereas compounds 3d and 3j containing resorcinolic rings
      were competitive inhibitors. The preliminary evaluation results of acute toxicity
      showed the representative 3d and 3j were non-toxic in mice dosed at 1,200 mg/kg.
      This research suggests that, with the advantage of being readily prepared small
      molecules, polyphenolic UCAs have the potential to develop into pharmacological
      inhibitors of tyrosinase.

PMID- 23552907
TI  - Atypical antipsychotics in the treatment of children and adolescents with
      pervasive developmental disorders.
AB  - RATIONALE: Autism and related pervasive developmental disorders (PDD) are
      characterized by impairments in social interaction and communication, restricted
      interests, and repetitive and stereotyped patterns of behavior. Individuals with
      PDD frequently display irritability and disruptive behaviors including tantrums,
      self-injurious behavior, and aggression. Atypical antipsychotics are currently
      the most efficacious pharmacological interventions available for treatment of
      irritability associated with PDD. OBJECTIVES: This article aims to review the
      body of literature pertaining to the use of atypical antipsychotics in the
      treatment of patients with PDD. METHODS: A PubMed literature search was conducted
      using the following key words: autism, pervasive developmental disorders,
      atypical antipsychotics, risperidone, aripiprazole, quetiapine, ziprasidone,
      olanzapine, clozapine, paliperidone, iloperidone, asenapine, and lurasidone.
      Search terms were limited to English language, human subjects, and publication
      from 1999 to present. Relevant references from identified articles were also
      reviewed. RESULTS: The efficacy and tolerability of risperidone and aripiprazole
      for the treatment of irritability in autism have been established with multi
      site, randomized, controlled trials. Studies supporting the use of other atypical
      antipsychotics are either limited in scope or less robust in their findings,
      though newer agents such as ziprasidone and paliperidone show promise.
      CONCLUSIONS: Atypical antipsychotics are currently first-line pharmacological
      agents for the treatment of irritability and associated behaviors in children
      with PDD. Further placebo-controlled studies are warranted to characterize the
      efficacy and tolerability of the majority of these medications. There is also a
      need for the development of novel, targeted drugs with more favorable long-term
      side effect profiles.

PMID- 23552908
TI  - Adsorption of diferrocenylacetylene on Au(111) studied by scanning tunneling
      microscopy.
AB  - Scanning tunneling microscopy images of diferrocenylacetylene (DFA) coadsorbed
      with benzene on Au(111) show individual and close-packed DFA molecules, either
      adsorbed alongside benzene or on top of a benzene monolayer. Images acquired over
      a range of positive and negative tip-sample bias voltages show a shift in
      contrast, with the acetylene linker appearing brighter than the ferrocenes at
      positive sample bias (where unoccupied states primarily contribute) and the
      reverse contrast at negative bias. Density functional theory was used to
      calculate the electronic structure of the gas-phase DFA molecule, and simulated
      images produced through two-dimensional projections of these calculations
      approximate the experimental images. The symmetry of both experimental and
      calculated molecular features for DFA rules out a cis adsorption geometry, and
      comparison of experiment to simulation indicates torsion around the inter
      ferrocene axis between 90 degrees  and 180 degrees  (trans); the cyclopentadienyl
      rings are thus angled with respect to the surface.

PMID- 23552909
TI  - Timing may not be everything.

PMID- 23552910
TI  - If a job is worth doing, it is worth doing twice.

PMID- 23552922
TI  - Crick's medal goes under the hammer.

PMID- 23552923
TI  - Sizing up a slow assault on cancer.

PMID- 23552924
TI  - Detectors zero in on Earth's heat.

PMID- 23552925
TI  - Detective work uncovers under-reported overfishing.

PMID- 23552926
TI  - Astrophysics: Fire in the hole!

PMID- 23552927
TI  - Policy: Update the Chemical Weapons Convention.

PMID- 23552928
TI  - Collaboration: Link the world's best investigators.

PMID- 23552933
TI  - Sexism: Dearth of female role models.

PMID- 23552934
TI  - Gender gap: Nature's readers comment online.

PMID- 23552935
TI  - Sexism: A revealing experiment.

PMID- 23552936
TI  - Donald Arthur Glaser (1926-2013).

PMID- 23552937
TI  - Biochemistry: Positive and radical.

PMID- 23552938
TI  - Earth science: Western North America's jigsaw.

PMID- 23552939
TI  - Cancer: A metabolic metamorphosis.

PMID- 23552940
TI  - Materials science: The same, but better.

PMID- 23552941
TI  - Biochemistry: Sirtuin on a high-fat diet.

PMID- 23552943
TI  - Patterns and mechanisms of early Pliocene warmth.
AB  - About five to four million years ago, in the early Pliocene epoch, Earth had a
      warm, temperate climate. The gradual cooling that followed led to the
      establishment of modern temperature patterns, possibly in response to a decrease
      in atmospheric CO2 concentration, of the order of 100 parts per million, towards
      preindustrial values. Here we synthesize the available geochemical proxy records
      of sea surface temperature and show that, compared with that of today, the early
      Pliocene climate had substantially lower meridional and zonal temperature
      gradients but similar maximum ocean temperatures. Using an Earth system model, we
      show that none of the mechanisms currently proposed to explain Pliocene warmth
      can simultaneously reproduce all three crucial features. We suggest that a
      combination of several dynamical feedbacks underestimated in the models at
      present, such as those related to ocean mixing and cloud albedo, may have been
      responsible for these climate conditions.

PMID- 23552944
TI  - Intra-oceanic subduction shaped the assembly of Cordilleran North America.
AB  - The western quarter of North America consists of accreted terranes--crustal
      blocks added over the past 200 million years--but the reason for this is unclear.
      The widely accepted explanation posits that the oceanic Farallon plate acted as a
      conveyor belt, sweeping terranes into the continental margin while subducting
      under it. Here we show that this hypothesis, which fails to explain many terrane
      complexities, is also inconsistent with new tomographic images of lower-mantle
      slabs, and with their locations relative to plate reconstructions. We offer a
      reinterpretation of North American palaeogeography and test it quantitatively:
      collision events are clearly recorded by slab geometry, and can be time
      calibrated and reconciled with plate reconstructions and surface geology. The
      seas west of Cretaceous North America must have resembled today's western
      Pacific, strung with island arcs. All proto-Pacific plates initially subducted
      into almost stationary, intra-oceanic trenches, and accumulated below as massive
      vertical slab walls. Above the slabs, long-lived volcanic archipelagos and
      subduction complexes grew. Crustal accretion occurred when North America overrode
      the archipelagos, causing major episodes of Cordilleran mountain building.

PMID- 23552945
TI  - Femtosecond switching of magnetism via strongly correlated spin-charge quantum
      excitations.
AB  - The technological demand to push the gigahertz (10(9) hertz) switching speed
      limit of today's magnetic memory and logic devices into the terahertz (10(12)
      hertz) regime underlies the entire field of spin-electronics and integrated multi
      functional devices. This challenge is met by all-optical magnetic switching based
      on coherent spin manipulation. By analogy to femtosecond chemistry and
      photosynthetic dynamics--in which photoproducts of chemical and biochemical
      reactions can be influenced by creating suitable superpositions of molecular
      states--femtosecond-laser-excited coherence between electronic states can switch
      magnetic order by 'suddenly' breaking the delicate balance between competing
      phases of correlated materials: for example, manganites exhibiting colossal
      magneto-resistance suitable for applications. Here we show femtosecond (10(-15)
      seconds) photo-induced switching from antiferromagnetic to ferromagnetic ordering
      in Pr0.7Ca0.3MnO3, by observing the establishment (within about 120 femtoseconds)
      of a huge temperature-dependent magnetization with photo-excitation threshold
      behaviour absent in the optical reflectivity. The development of ferromagnetic
      correlations during the femtosecond laser pulse reveals an initial quantum
      coherent regime of magnetism, distinguished from the picosecond (10(-12) seconds)
      lattice-heating regime characterized by phase separation without threshold
      behaviour. Our simulations reproduce the nonlinear femtosecond spin generation
      and underpin fast quantum spin-flip fluctuations correlated with coherent
      superpositions of electronic states to initiate local ferromagnetic correlations.
      These results merge two fields, femtosecond magnetism in metals and band
      insulators, and non-equilibrium phase transitions of strongly correlated
      electrons, in which local interactions exceeding the kinetic energy produce a
      complex balance of competing orders.

PMID- 23552946
TI  - Colossal injection of catalyst atoms into silicon nanowires.
AB  - The incorporation of impurities during the growth of nanowires from the vapour
      phase alters their basic properties substantially, and this process is critical
      in an extended range of emerging nanometre-scale technologies. In particular,
      achieving precise control of the behaviour of group III and group V dopants has
      been a crucial step in the development of silicon (Si) nanowire-based devices.
      Recently it has been demonstrated that the use of aluminium (Al) as a growth
      catalyst, instead of the usual gold, also yields an effective p-type doping,
      thereby enabling a novel and efficient route to functionalizing Si nanowires.
      Besides the technological implications, this self-doping implies the detachment
      of Al from the catalyst and its injection into the growing nanowire, involving
      atomic-scale processes that are crucial for the fundamental understanding of the
      catalytic assembly of nanowires. Here we present an atomic-level, quantitative
      study of this phenomenon of catalyst dissolution by three-dimensional atom-by
      atom mapping of individual Al-catalysed Si nanowires using highly focused
      ultraviolet-laser-assisted atom-probe tomography. Although the observed
      incorporation of the catalyst atoms into nanowires exceeds by orders of magnitude
      the equilibrium solid solubility and solid-solution concentrations in known non
      equilibrium processes, the Al impurities are found to be homogeneously
      distributed in the nanowire and do not form precipitates or clusters. As well as
      the anticipated effect on the electrical properties, this kinetics-driven
      colossal injection also has direct implications for nanowire morphology. We
      discuss the observed strong deviation from equilibrium using a model of solute
      trapping at step edges, and identify the key growth parameters behind this
      phenomenon on the basis of a kinetic model of step-flow growth of nanowires. The
      control of this phenomenon provides opportunities to create a new class of
      nanoscale devices by precisely tailoring the shape and composition of metal
      catalysed nanowires.

PMID- 23552947
TI  - July 2012 Greenland melt extent enhanced by low-level liquid clouds.
AB  - Melting of the world's major ice sheets can affect human and environmental
      conditions by contributing to sea-level rise. In July 2012, an historically rare
      period of extended surface melting was observed across almost the entire
      Greenland ice sheet, raising questions about the frequency and spatial extent of
      such events. Here we show that low-level clouds consisting of liquid water
      droplets ('liquid clouds'), via their radiative effects, played a key part in
      this melt event by increasing near-surface temperatures. We used a suite of
      surface-based observations, remote sensing data, and a surface energy-balance
      model. At the critical surface melt time, the clouds were optically thick enough
      and low enough to enhance the downwelling infrared flux at the surface. At the
      same time they were optically thin enough to allow sufficient solar radiation to
      penetrate through them and raise surface temperatures above the melting point.
      Outside this narrow range in cloud optical thickness, the radiative contribution
      to the surface energy budget would have been diminished, and the spatial extent
      of this melting event would have been smaller. We further show that these thin,
      low-level liquid clouds occur frequently, both over Greenland and across the
      Arctic, being present around 30-50 per cent of the time. Our results may help to
      explain the difficulties that global climate models have in simulating the Arctic
      surface energy budget, particularly as models tend to under-predict the formation
      of optically thin liquid clouds at supercooled temperatures--a process
      potentially necessary to account fully for temperature feedbacks in a warming
      Arctic climate.

PMID- 23552948
TI  - The emergence of functional microcircuits in visual cortex.
AB  - Sensory processing occurs in neocortical microcircuits in which synaptic
      connectivity is highly structured and excitatory neurons form subnetworks that
      process related sensory information. However, the developmental mechanisms
      underlying the formation of functionally organized connectivity in cortical
      microcircuits remain unknown. Here we directly relate patterns of excitatory
      synaptic connectivity to visual response properties of neighbouring layer 2/3
      pyramidal neurons in mouse visual cortex at different postnatal ages, using two
      photon calcium imaging in vivo and multiple whole-cell recordings in vitro.
      Although neural responses were already highly selective for visual stimuli at eye
      opening, neurons responding to similar visual features were not yet
      preferentially connected, indicating that the emergence of feature selectivity
      does not depend on the precise arrangement of local synaptic connections. After
      eye opening, local connectivity reorganized extensively: more connections formed
      selectively between neurons with similar visual responses and connections were
      eliminated between visually unresponsive neurons, but the overall connectivity
      rate did not change. We propose a sequential model of cortical microcircuit
      development based on activity-dependent mechanisms of plasticity whereby neurons
      first acquire feature preference by selecting feedforward inputs before the onset
      of sensory experience--a process that may be facilitated by early electrical
      coupling between neuronal subsets--and then patterned input drives the formation
      of functional subnetworks through a redistribution of recurrent synaptic
      connections.

PMID- 23552949
TI  - SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl
      lysine.
AB  - The Sir2 family of enzymes or sirtuins are known as nicotinamide adenine
      dinucleotide (NAD)-dependent deacetylases and have been implicated in the
      regulation of transcription, genome stability, metabolism and lifespan. However,
      four of the seven mammalian sirtuins have very weak deacetylase activity in
      vitro. Here we show that human SIRT6 efficiently removes long-chain fatty acyl
      groups, such as myristoyl, from lysine residues. The crystal structure of SIRT6
      reveals a large hydrophobic pocket that can accommodate long-chain fatty acyl
      groups. We demonstrate further that SIRT6 promotes the secretion of tumour
      necrosis factor-alpha (TNF-alpha) by removing the fatty acyl modification on K19
      and K20 of TNF-alpha. Protein lysine fatty acylation has been known to occur in
      mammalian cells, but the function and regulatory mechanisms of this modification
      were unknown. Our data indicate that protein lysine fatty acylation is a novel
      mechanism that regulates protein secretion. The discovery of SIRT6 as an enzyme
      that controls protein lysine fatty acylation provides new opportunities to
      investigate the physiological function of a protein post-translational
      modification that has been little studied until now.

PMID- 23552950
TI  - Mechanistic studies of an unprecedented enzyme-catalysed 1,2-phosphono-migration
      reaction.
AB  - (S)-2-hydroxypropylphosphonate ((S)-2-HPP) epoxidase (HppE) is a mononuclear non
      haem-iron-dependent enzyme responsible for the final step in the biosynthesis of
      the clinically useful antibiotic fosfomycin. Enzymes of this class typically
      catalyse oxygenation reactions that proceed via the formation of substrate
      radical intermediates. By contrast, HppE catalyses an unusual dehydrogenation
      reaction while converting the secondary alcohol of (S)-2-HPP to the epoxide ring
      of fosfomycin. Here we show that HppE also catalyses a biologically unprecedented
      1,2-phosphono migration with the alternative substrate (R)-1-HPP. This
      transformation probably involves an intermediary carbocation, based on
      observations with additional substrate analogues, such as (1R)-1-hydroxyl-2
      aminopropylphosphonate, and model reactions for both radical- and carbocation
      mediated migration. The ability of HppE to catalyse distinct reactions depending
      on the regio- and stereochemical properties of the substrate is given a
      structural basis using X-ray crystallography. These results provide compelling
      evidence for the formation of a substrate-derived cation intermediate in the
      catalytic cycle of a mononuclear non-haem-iron-dependent enzyme. The underlying
      chemistry of this unusual phosphono migration may represent a new paradigm for
      the in vivo construction of phosphonate-containing natural products that can be
      exploited for the preparation of new phosphonate derivatives.

PMID- 23552952
TI  - Are killer cell immunoglobulin-like receptor genes important for the prediction
      of kidney graft rejection?
AB  - Killer cell immunoglobulin-like receptors (KIRs) are expressed on natural killer
      cells and minor subpopulations of thymus-derived (T) lymphocytes. KIRs may have a
      long cytoplasmic tail and inhibit cell activation upon ligand (HLA class I)
      binding, or they may have a short cytoplasmic tail and activate a cell after
      ligand binding. They are encoded by up to 14 genes present in different
      individuals in different combinations, whence their associations with several
      human diseases. KIR involvement in the fate of kidney allograft has not been
      extensively studied; nevertheless some associations had already been noticed.
      Their results are not concordant: some authors found no effect of KIR genotype,
      whereas others detected protective effect of KIR2DL2/KIR2DS2 or KIR-KIR ligand
      mismatch. We found an association of KIR2DS4 gene with acute rejection and a
      protective effect of KIR2DS5 gene. Interestingly, in patients, whose end-stage
      renal disease was caused by glomerulonephritis, the effect of KIR2DS4 was
      stronger than HLA mismatch, whereas opposite was true for recipients with other
      causes of renal failure. 

PMID- 23552953
TI  - Dissecting the genotype in syndromic intellectual disability using whole exome
      sequencing in addition to genome-wide copy number analysis.
AB  - When a known microimbalance affecting multiple genes is detected in a patient
      with syndromic intellectual disability, it is usually presumed causative for all
      observed features. Whole exome sequencing (WES) allows questioning this
      assumption. In this study of three families with children affected by unexplained
      syndromic intellectual disability, genome-wide copy number and subsequent
      analyses revealed a de novo maternal 1.1 Mb microdeletion in the 14q32 imprinted
      region causing a paternal UPD(14)-like phenotype, and two inherited 22q11.21
      microduplications of 2.5 or 2.8 Mb. In patient 1 carrying the 14q32
      microdeletion, tall stature and renal malformation were unexplained by paternal
      UPD(14), and there was no altered DLK1 expression or unexpected methylation
      status. By WES and filtering with a mining tool, a novel FBN1 missense variant
      was found in patient 1 and his mother, who both showed clinical features of
      Marfan syndrome by thorough anthropometric assessment, and a novel EYA1 missense
      variant as a probable cause of the renal malformation in the patient. In patient
      2 with the 22q11.21 microduplication syndrome, skin hypo- and hyperpigmentation
      and two malignancies were only partially explained. By WES, compound heterozygous
      BLM stop founder mutations were detected causing Bloom syndrome. In male patient
      3 carrying a 22q11.21 microduplication inherited from his unaffected father, WES
      identified a novel missense variant in the OPHN1 X-linked intellectual disability
      gene inherited from the unaffected mother as a possible additional cause for
      developmental delay. Thus, WES seems warranted in patients carrying
      microdeletions or microduplications, who have unexplained clinical features or
      microimbalances inherited from an unaffected parent.

PMID- 23552954
TI  - The complex genetic landscape of familial breast cancer.
AB  - Familial breast cancer represents a minor percentage of all human breast cancers.
      Mutations in two high susceptibility genes BRCA1 and BRCA2 explain around 25 % of
      familial breast cancers, while other high, moderate and low susceptibility genes
      explain up to 20 % more of breast cancer families. Thus, it is important to
      decipher the genetic architecture of families that show no mutations to improve
      genetic counselling. The comprehensive description of familial breast cancer
      using different techniques and platforms has shown to be very valuable for better
      patient diagnosis, tumour surveillance, and ultimately patient treatment. This
      review focuses on the complex landscape of pathological, protein, genetic and
      genomic features associated with BRCA1-, BRCA2-, and non-BRCA1/BRCA2-related
      cancers described up to date. Special emphasis deserves the coexistence of
      distinct molecular breast cancer subtypes, the development of tumour classifiers
      to predict BRCA1/2 mutations, and the last insights from recent whole genome
      sequencing studies and miRNA profiling. 

PMID- 23552957
TI  - Taking a broader perspective on the benefits of minimally invasive surgery.

PMID- 23552956
TI  - Fetal surgical intervention: progress and perspectives.
AB  - Building upon over 30 years of experimental and clinical development, fetal
      surgery can be argued to be a standard of care for selected indications, though
      application of these techniques remains limited to a small number of highly
      selected fetuses, and availability to a small number of highly specialized
      centers. Despite its limited application to date, the field of fetal surgery
      continues to evolve, spurred both by technological advances allowing earlier and
      more accurate diagnosis of fetal anomalies as well as improved capability to
      intervene when appropriate. The efficacy of fetal surgical intervention has now
      been validated for selected indications by well-designed, randomized controlled
      trials. In this review, we summarize the evidence or lack thereof supporting the
      current most common indications for fetal surgical intervention.

PMID- 23552958
TI  - Summaries for patients. Mobility impairment reduces access to subspecialty care.

PMID- 23552959
TI  - Atomistic simulations of highly conductive molecular transport junctions under
      realistic conditions.
AB  - We report state-of-the-art atomistic simulations combined with high-fidelity
      conductance calculations to probe structure-conductance relationships in Au
      benzenedithiolate (BDT)-Au junctions under elongation. Our results demonstrate
      that large increases in conductance are associated with the formation of
      monatomic chains (MACs) of Au atoms directly connected to BDT. An analysis of the
      electronic structure of the simulated junctions reveals that enhancement in the s
      like states in Au MACs causes the increases in conductance. Other structures also
      result in increased conductance but are too short-lived to be detected in
      experiment, while MACs remain stable for long simulation times. Examinations of
      thermally evolved junctions with and without MACs show negligible overlap between
      conductance histograms, indicating that the increase in conductance is related to
      this unique structural change and not thermal fluctuation. These results, which
      provide an excellent explanation for a recently observed anomalous experimental
      result [Bruot et al., Nat. Nanotechnol., 2012, 7, 35-40], should aid in the
      development of mechanically responsive molecular electronic devices.

PMID- 23552960
TI  - ACP Journal Club. Parenteral hydration did not improve dehydration or quality of
      life in advanced cancer.

PMID- 23552961
TI  - Duchenne muscular dystrophy fibroblast nodules: a cell-based assay for screening
      anti-fibrotic agents.
AB  - Severe muscle fibrosis is the endpoint of many chronic myopathies. Identification
      of factors that regulate fibrosis is important for understanding its pathogenesis
      and for developing anti-fibrotic treatments that prevent muscle destruction. We
      have developed an in vitro model for screening potential anti-fibrotic agents.
      The model consists of three-dimensional clusters (nodules) of fibroblasts derived
      from Duchenne muscular dystrophy (DMD) muscle. The primary fibroblasts
      spontaneously and quickly form nodules resembling fibrotic foci (cells plus
      extracellular matrix) when grown on a solid substrate. We tested the anti
      fibrotic action of suramin, decorin, and spironolactone (all with established
      anti-fibrotic activity) on the model. All three agents significantly reduced
      nodule number, and spironolactone and suramin significantly reduced nodule
      diameter. Nodule secretion of soluble collagen was also significantly reduced by
      decorin and spironolactone treatment, whereas suramin had no significant effect.
      Collagen I and fibronectin protein expression was significantly reduced in the
      culture medium of control and DMD fibroblasts by spironolactone treatment, but
      not by decorin and suramin treatment. Finally, in DMD fibroblast monolayers,
      collagen deposition was significantly reduced by all three agents. Spironolactone
      significantly reduced collagen I and fibronectin transcript levels, whereas
      decorin reduced only fibronectin. Our in vitro model of fibrogenesis has thus
      revealed differing anti-fibrotic effects in the three anti-fibrotic agents
      tested. It therefore appears as a useful and sensitive system for the testing of
      anti-fibrotic drugs and could be adapted for the high-throughput screening of new
      anti-fibrotic molecules.

PMID- 23552963
TI  - Tunable electronic and dielectric behavior of GaS and GaSe monolayers.
AB  - Here we present first-principles calculations to investigate systematically the
      electronic behavior and the electron energy low-loss spectra (EELS) of monolayer,
      bilayer, four-layer, and bulk configurations of periodic GaX (X = S, Se), as well
      as the effect of mechanical strain on the electronic properties of the GaX
      monolayer. We predicate that the GaX monolayer is a semiconductor with an
      indirect band gap, however, the difference between the direct and indirect gaps
      is so small that electrons can transfer easily between this minimum with a small
      amount of thermal energy. Owning to strong surface effects, the electronic and
      dielectric properties of GaX vary drastically with number of layers in a sheet.
      In detail, the band gap increases from multilayer-to-single layer and EELS shifts
      towards larger wavelengths with a decrease in the layer thickness. Moreover, we
      demonstrate that the band gaps of GaX monolayers can be widely tuned by
      mechanical deformation, making them potential candidates for tunable nanodevices.
      The present study provides theoretical insight leading to a better understanding
      of these novel 2D structures.

PMID- 23552964
TI  - Light driven ultrafast electron transfer in oxidative redding of Green
      Fluorescent Proteins.
AB  - Fluorescent proteins undergoing green to red (G/R) photoconversion have proved to
      be potential tools for investigating dynamic processes in living cells and for
      photo-localization nanoscopy. However, the photochemical reaction during light
      induced G/R photoconversion of fluorescent proteins remains unclear. Here we
      report the direct observation of ultrafast time-resolved electron transfer (ET)
      during the photoexcitation of the fluorescent proteins EGFP and mEos2 in presence
      of electron acceptor, p-benzoquinone (BQ). Our results show that in the excited
      state, the neutral EGFP chromophore accepts electrons from an anionic electron
      donor, Glu222, and G/R photoconversion is facilitated by ET to nearby electron
      acceptors. By contrast, mEos2 fails to produce the red emitting state in the
      presence of BQ; ET depletes the excited state configuration en route to the red
      emitting fluorophore. These results show that ultrafast ET plays a pivotal role
      in multiple photoconversion mechanisms and provide a method to modulate the G/R
      photoconversion process.

PMID- 23552965
TI  - Anti-Bredt N-heterocyclic carbene: an efficient ligand for the gold(I)-catalyzed
      hydroamination of terminal alkynes with parent hydrazine.
AB  - An anti-Bredt N-heterocyclic carbene gold(I) chloride complex was synthesized by
      taking advantage of the reversible insertion of the free carbene into the NH bond
      of hexamethyldisilazane. This precatalyst promotes the parent hydrazine
      hydroamination of terminal alkynes at room temperature.

PMID- 23552962
TI  - Skeletal muscle hypertrophy and regeneration: interplay between the myogenic
      regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways.
AB  - Adult skeletal muscle can regenerate in response to muscle damage. This ability
      is conferred by the presence of myogenic stem cells called satellite cells. In
      response to stimuli such as injury or exercise, these cells become activated and
      express myogenic regulatory factors (MRFs), i.e., transcription factors of the
      myogenic lineage including Myf5, MyoD, myogenin, and Mrf4 to proliferate and
      differentiate into myofibers. The MRF family of proteins controls the
      transcription of important muscle-specific proteins such as myosin heavy chain
      and muscle creatine kinase. Different growth factors are secreted during muscle
      repair among which insulin-like growth factors (IGFs) are the only ones that
      promote both muscle cell proliferation and differentiation and that play a key
      role in muscle regeneration and hypertrophy. Different isoforms of IGFs are
      expressed during muscle repair: IGF-IEa, IGF-IEb, or IGF-IEc (also known as
      mechano growth factor, MGF) and IGF-II. MGF is expressed first and is observed in
      satellite cells and in proliferating myoblasts whereas IGF-Ia and IGF-II
      expression occurs at the state of muscle fiber formation. Interestingly, several
      studies report the induction of MRFs in response to IGFs stimulation. Inversely,
      IGFs expression may also be regulated by MRFs. Various mechanisms are proposed to
      support these interactions. In this review, we describe the general process of
      muscle hypertrophy and regeneration and decipher the interactions between the two
      groups of factors involved in the process.

PMID- 23552967
TI  - Complete resolution of chronic multiple verruca vulgaris treated with
      quadrivalent human papillomavirus vaccine.

PMID- 23552968
TI  - Indications, complications, and management of inferior vena cava filters: the
      experience in 952 patients at an academic hospital with a level I trauma center.
AB  - IMPORTANCE: Retrievable inferior vena cava (IVC) filters were designed to provide
      temporary protection from pulmonary embolism, sparing patients from long-term
      complications of permanent filters. However, many retrievable IVC filters are
      left in place indefinitely. OBJECTIVES: To review the medical records of patients
      with IVC filters to determine patient demographics and date of and indication for
      IVC filter placement, as well as complications, follow-up data, date of IVC
      filter retrieval, and use of anticoagulant therapy. DESIGN AND SETTING: A
      retrospective review of IVC filter use between August 1, 2003, and February 28,
      2011, was conducted at Boston Medical Center, a tertiary referral center with the
      largest trauma center in New England. PARTICIPANTS: In total, 978 patients.
      Twenty six patients were excluded from the study because of incomplete medical
      records. INTERVENTION: Placement of retrievable IVC filter. MAIN OUTCOME
      MEASURES: In total, 952 medical records were included in the analysis. RESULTS:
      Of 679 retrievable IVC filters that were placed, 58 (8.5%) were successfully
      removed. Unsuccessful retrieval attempts were made in 13 patients (18.3% of
      attempts). Seventy-four venous thrombotic events (7.8% of 952 patients included
      in the study) occurred after IVC filter placement, including 25 pulmonary emboli,
      all of which occurred with the IVC filter in place. Forty-eight percent of venous
      thrombotic events were in patients without venous thromboembolism at the time of
      IVC filter placement, and 89.4% occurred in patients not receiving
      anticoagulants. Many IVC filters placed after trauma were inserted when the
      highest bleeding risk had subsided, and anticoagulant therapy may have been
      appropriate. While many of these filters were placed because of a perceived
      contraindication to anticoagulants, 237 patients (24.9%) were discharged on a
      regimen of anticoagulant therapy. CONCLUSION AND RELEVANCE: Our research suggests
      that the use of IVC filters for prophylaxis and treatment of venous thrombotic
      events, combined with a low retrieval rate and inconsistent use of anticoagulant
      therapy, results in suboptimal outcomes due to high rates of venous
      thromboembolism.

PMID- 23552969
TI  - Multiple asymptomatic violaceous macules on the thigh. Multinucleate cell
      angiohistiocytoma (MCAH).

PMID- 23552970
TI  - The development and implementation of quality assurance programs to support
      nutritional measurements.
AB  - The National Institute of Standards and Technology administers quality assurance
      programs devoted to improving measurements of nutrients and related metabolites
      in foods, dietary supplements, and serum and plasma samples. These programs have
      been developed in collaboration with the National Institutes of Health to assist
      measurement communities in their efforts to achieve accurate results that are
      comparable among different laboratories and over time. Targeted analytes include
      micronutrients, botanical markers, nutritional elements, contaminants, fatty
      acids, and vitamin D metabolites.

PMID- 23552971
TI  - A photoinduced electron transfer-based nanoprobe as a marker of acidic organelles
      in mammalian cells.
AB  - Photoinduced electron transfer (PET)-based molecular probes have been
      successfully used for the intracellular imaging of the pH of acidic organelles.
      In this study, we describe the synthesis and characterization of a novel PET
      based pH nanoprobe and its biological application for the signaling of acidic
      organelles in mammalian cells. A fluorescent ligand sensitive to pH via the PET
      mechanism that incorporates a thiolated moiety was synthesized and used to
      stabilize gold nanoparticles (2.4 +/- 0.6 nm), yielding a PET-based nanoprobe.
      The PET nanoprobe was unambiguously characterized by transmission electron
      microscopy, proton nuclear magnetic resonance, Fourier transform infrared,
      ultraviolet-visible absorption, and steady-state/time-resolved fluorescence
      spectroscopies which confirmed the functionalization of the gold nanoparticles
      with the PET-based ligand. Following a classic PET behavior, the fluorescence
      emission of the PET-based nanoprobe was quenched in alkaline conditions and
      enhanced in an acidic environment. The PET-based nanoprobe was used for the
      intracellular imaging of acidic environments within Chinese hamster ovary cells
      by confocal laser scanning microscopy. The internalization of the nanoparticles
      by the cells was confirmed by confocal fluorescence images and also by recording
      the fluorescence emission spectra of the intracellular PET-based nanoprobe from
      within the cells. Co-localization experiments using a marker of acidic
      organelles, LysoTracker Red DND-99, and a marker of autophagosomes, GFP-LC3,
      confirm that the PET-based nanoprobe acts as marker of acidic organelles and
      autophagosomes within mammalian cells.

PMID- 23552972
TI  - Determining urea levels in dialysis human serum by means of headspace solid phase
      microextraction coupled with ion mobility spectrometry and on the basis of
      nanostructured polypyrrole film.
AB  - A simple and sensitive headspace (HS) solid phase microextraction (SPME) coupled
      with ion mobility spectrometry (IMS) method is presented for analysis of urea in
      dialysis human serum samples. A dodecylbenzenesulfonate-doped polypyrrole coating
      was used as a fiber for SPME. The HS-SPME-IMS method exhibits good repeatability
      (relative standard deviation of 3% or less), simplicity, and good sensitivity.
      The influence of various analytical parameters such as pH, ionic strength,
      extraction time and temperature was investigated and the parameters were
      optimized. The calibration graph was linear in the range from 5 to 50 MUg mL(-1),
      and the detection limit was 2 MUg mL(-1). The method was applied successfully for
      determination of urea in human serum and with acceptable recovery (more than
      98%). Finally, a standard addition calibration method was applied to the HS-SPME
      IMS method for the analysis of human serum samples before and at the end of
      dialysis. The proposed method appears to be suitable for the analysis of urea in
      serum samples as it is not time-consuming and requires only small quantities of
      the sample without any derivatization process.

PMID- 23552973
TI  - Preparation of a boronate-functionalized affinity hybrid monolith for specific
      capture of glycoproteins.
AB  - A novel strategy for preparation of a boronate affinity hybrid monolith was
      developed using a Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC)
      reaction of an alkyne-boronate ligand with an azide-functionalized monolithic
      intermediate. An azide-functionalized hybrid monolith was first synthesized via a
      single-step procedure to provide reactive sites for click chemistry; then the
      alkyne-boronate ligands were covalently immobilized on the azide-functionalized
      hybrid monolith via an in-column CuAAC reaction to form a boronate affinity
      hybrid monolith under mild conditions. The boronate affinity monolith was
      characterized and evaluated by means of elemental analysis, Fourier transform
      infrared spectroscopy, and scanning electron microscopy. The boronate affinity
      hybrid monolith exhibited excellent specificity toward nucleosides and
      glycoproteins, which were chosen as test cis-diol-containing compounds under
      neutral conditions. The binding capacity of the monolith for the glycoprotein
      ovalbumin was 2.36 mg . g(-1) at pH 7.0. The practicability of the boronate
      affinity hybrid monolithic material was demonstrated by specific capture of the
      glycoproteins ovalbumin and ovotransferrin from an egg sample.

PMID- 23552974
TI  - Investigation of the biotransformation of melarsoprol by electrochemistry coupled
      to complementary LC/ESI-MS and LC/ICP-MS analysis.
AB  - Melarsoprol is the only currently available drug for treatment of the late stage
      of African trypanosomiasis (sleeping sickness). Unfortunately, the arsenic
      containing drug causes serious side effects, for which the mechanisms have not
      been elucidated so far. This investigation describes the study of the melarsoprol
      biotransformation processes by electrochemical (EC) techniques. Based on EC,
      potential oxidation reactions of melarsoprol are examined. Moreover, the
      reactivity of melarsoprol, its metabolite melarsen oxide, and their oxidation
      products toward the tripeptide glutathione and the proteins hemoglobin and human
      serum albumin is evaluated. The combination of different analytical techniques
      allows the identification as well as the quantification of the biotransformation
      products. The hyphenation of liquid chromatography (LC) and electrospray
      ionization mass spectrometry (ESI-MS) is applied for identification and structure
      elucidation, which implies the determination of exact masses and fragmentation
      patterns. For the selective detection of arsenic containing metabolites, LC
      coupled to inductively coupled plasma mass spectrometry is utilized. Based on the
      obtained data, the oxidative biotransformation of melarsoprol can be predicted,
      revealing novel species which have been suspected, but not been identified up to
      now. The results of the protein studies prove that melarsen oxide, the active
      derivative of melarsoprol, strongly binds to human hemoglobin and forms different
      adducts via the free cysteinyl groups of the hemoglobin alpha- and beta-chain.

PMID- 23552975
TI  - Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis.

PMID- 23552976
TI  - Brief self-report measure of work-related cognitive limitations in breast cancer
      survivors.
AB  - PURPOSE: The purpose of this research was to develop a brief, reliable self
      report measure of work-related cognitive limitations in occupationally active
      breast cancer survivors. METHODS: A pooled dataset of working breast cancer
      survivors (n = 228) completed a self-report measure of work-related cognitive
      limitations, the Cognitive Symptom Checklist-Work-59 (CSC-W59). A cross
      validation technique was employed such that the pooled participants were
      randomized into two separate groups in order to conduct exploratory factor
      analysis (EFA) of the CSC-W59 with one group (n = 114) and confirm the results
      with the second group (n = 114). RESULTS: EFA of the CSC-W59 identified 21 items
      with a consistent factor loading of .4 or higher on three separate subscales
      (Working Memory, Executive Function, and Task Completion). These findings
      resulted in a 21-item, self-report measure referred to as the Cognitive Symptom
      Checklist-Work-21 (CSC-W21). The CSC-W21 demonstrated internal reliability (alpha
      = .88). Construct validity of the CSC-W21 is supported by significant positive
      correlations with cancer stage, job stress, and affective state. CONCLUSIONS:
      Brief, valid, internally reliable self-report measures such as the CSC-W21 may be
      used to quickly assess work-related cognitive problems for breast cancer
      survivors at work. IMPLICATIONS FOR CANCER SURVIVORS: A brief measure is
      available to help identify tasks that present problems for breast cancer
      survivors who are at work. This measure can be used to facilitate research to
      improve the understanding and mitigation of cognitive challenges in breast cancer
      survivors in the work setting.

PMID- 23552977
TI  - Epidemiological, clinical, and molecular study of a cohort of Italian Parkinson
      disease patients: association with glutathione-S-transferase and DNA repair gene
      polymorphisms.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disorders
      whose etiology is multifactorial including both hereditary and environmental
      factors. Currently, pathogenic mutations in at least five genes have been
      implicated in familial PD generally accounting for less than 10 % of all PD cases
      in most populations. It has been suggested that polymorphisms in other genes such
      as those encoding enzymes involved in oxidative metabolism and detoxification
      could be involved in predisposition to PD since oxidative stress in dopaminergic
      neurons is thought to be of central importance in the pathogenesis of the
      disease. The aim of our work was to study the association of genetic
      polymorphisms in genes involved in oxidative metabolism and detoxification
      mechanism, namely GSTM1, GSTT1, GSTP1, and those involved in DNA damage repair,
      OGG1 and XRCC1, in an Italian cohort of sporadic PD patients. We did not detect
      any association between GSTT1 and GTTM1 null polymorphisms and PD, whereas the
      104GSTP1 polymorphism was associated with PD in male patients but not in females.
      Furthermore, we detected a protective effect of wild type genotype of XRCC1 in
      women.

PMID- 23552978
TI  - [Genetic fever syndromes. Hereditary recurrent (periodic) fever syndromes].
AB  - Genetic fever syndromes or hereditary recurrent fever syndromes (HRF) are
      considered to be part of the autoinflammatory diseases (AID) which result from
      errors in the innate immune system. Patients typically have self-limiting
      episodes of fever and high levels of inflammation markers. The mode of
      inheritance is autosomal recessive or autosomal dominant. The diseases of the HRF
      include familial Mediterranean fever, tumor necrosis factor receptor 1-associated
      periodic syndrome, hyper-IgD syndrome and cryopyrin-associated periodic fever
      syndromes. The disease known as deficiency of interleukin 1 (IL1) receptor
      antagonist does not fully belong to this group because fever is not a typical
      symptom. The therapy depends on the type and severity of the disease. Effective
      prophylaxis is possible for FMF. Biologicals, especially IL1 blocking agents are
      highly effective in very severe fever syndromes. In order to collect more
      information on AID, to establish a biobank and coordinate research in this field
      the AID-Net project was founded. Currently 606 patients with AID are registered
      of whom 381 have HRF.

PMID- 23552979
TI  - [Pachydermodactyly].
AB  - The differential diagnosis of swelling of the small finger joints is broad. We
      report on two young men presenting with progressive painless swelling of the
      proximal interphalangeal (PIP) joints where the physical examination was
      otherwise inconspicuous. Laboratory investigations including auto- antibodies
      were all normal, x-rays and magnetic resonance imaging (MRI) revealed no joint
      pathologies but only increased skin thickening. Skin biopsy demonstrated
      hyperkeratosis and acanthosis without tissue inflammation. We thus diagnosed
      pachydermodactyly in both cases. This rare disease predominantly affects young
      males, can affect one or both hands and is often associated with mechanical
      stress due to repetitive movements in patients with obsessive-compulsive
      disorders. Occupational exposure by monotonous actions (e.g. poultry processing)
      may also be a cause. A specific therapy is unnecessary in most cases but may
      include intralesional steroid administration or surgical resection. Cessation of
      mechanical stress can significantly improve pachydermodactyly.

PMID- 23552980
TI  - [Long-term data from the CYCLOPS study].

PMID- 23552981
TI  - Disease modification in systemic sclerosis. Do integrated approaches offer new
      challenges?

PMID- 23552984
TI  - ACP Journal Club. Review: adding corticosteroids to antibiotics improves pain
      relief in patients with sore throat.

PMID- 23552982
TI  - Predictive factors of postoperative mortality after junctional and gastric
      adenocarcinoma resection.
AB  - IMPORTANCE: Postoperative mortality after junctional and gastric adenocarcinoma
      resection remains a significant issue. OBJECTIVE: To identify factors predictive
      of mortality within 30 days of junctional and gastric adenocarcinoma resection in
      a large national multicenter cohort. DESIGN: A retrospective study collecting
      data from a multicenter database of patients who underwent resection for
      junctional and gastric adenocarcinoma from January 1, 1997, through January 31,
      2010. A stepwise logistic regression model was built to identify, by multivariate
      analysis, variables independently predictive of 30-day postoperative mortality
      (POM). SETTING: Nineteen university teaching hospitals in France. PARTICIPANTS:
      Two thousand six hundred seventy patients with available data. MAIN OUTCOME
      MEASURES: The primary end point was POM. Secondary end points included (1) late
      mortality (30-90 days after resection) and (2) postoperative morbidity. RESULTS:
      One thousand eight hundred ninety-six patients (71.01%) had gastric
      adenocarcinoma and 774 (28.99%) had junctional tumors. Neoadjuvant treatment was
      given to 655 patients (24.53%), and 114 patients (4.27%) died within 30 days of
      surgery. Postoperative mortality was higher in patients who experienced grades
      III and IV toxic effects during neoadjuvant treatment compared with those who did
      not (8.7% vs 2.9%, respectively; P = .007). Multivariate analysis revealed
      metastatic disease at diagnosis (odds ratio, 9.13 [95% CI, 3.29-25.35]; P < .001)
      and poor tolerance of neoadjuvant treatment (3.33 [1.25-8.85]; P = .02) as being
      independently predictive of POM. Centers performing at least 10 resections per
      year were found to be protective against POM (odds ratio, 0.29 [95% CI, 0.12
      0.72]; P = .008). CONCLUSIONS AND RELEVANCE: This large national cohort study
      confirms that advanced disease heightens the risk of POM; centralization of
      junctional and gastric adenocarcinoma resection is warranted. The novel finding
      that grades III to IV toxic effects during neoadjuvant therapy increase POM has
      significant implications for decision making in this subgroup of patients. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01249859.

PMID- 23552985
TI  - Temporal variation in site fidelity: scale-dependent effects of forage abundance
      and predation risk in a non-migratory large herbivore.
AB  - Large herbivores are typically confronted by considerable spatial and temporal
      variation in forage abundance and predation risk. Although animals can employ a
      range of behaviours to balance these limiting factors, scale-dependent movement
      patterns are expected to be an effective strategy to reduce predation risk and
      optimise foraging opportunities. We tested this prediction by quantifying site
      fidelity of global positioning system-collared, non-migratory female elk (Cervus
      canadensis manitobensis) across multiple nested temporal scales using a long
      established elk-wolf (Canis lupus) system in Manitoba, Canada. Using a
      hierarchical analytical approach, we determined the combined effect of forage
      abundance and predation risk on variation in site fidelity within four seasons
      across four nested temporal scales: monthly, biweekly, weekly, daily. Site
      fidelity of female elk was positively related to forage-rich habitat across all
      seasons and most temporal scales. At the biweekly, weekly and daily scales, elk
      became increasingly attached to low forage habitat when risk was high (e.g. when
      wolves were close or pack sizes were large), which supports the notion that
      predator-avoidance movements lead to a trade-off between energetic requirements
      and safety. Unexpectedly, predation risk at the monthly scale increased fidelity,
      which may indicate that elk use multiple behavioural responses (e.g. movement,
      vigilance, and aggregation) simultaneously to dilute predation risk, especially
      at longer temporal scales. Our study clearly shows that forage abundance and
      predation risk are important scale-dependent determinants of variation in site
      fidelity of non-migratory female elk and that their combined effect is most
      apparent at short temporal scales. Insight into the scale-dependent behavioural
      responses of ungulate populations to limiting factors such as predation risk and
      forage variability is essential to infer the fitness costs incurred. 

PMID- 23552986
TI  - Management practices and the quality of care in cardiac units.
AB  - IMPORTANCE: To improve the quality of health care, many researchers have
      suggested that health care institutions adopt management approaches that have
      been successful in the manufacturing and technology sectors. However, relatively
      little information exists about how these practices are disseminated in hospitals
      and whether they are associated with better performance. OBJECTIVES: To describe
      the variation in management practices among a large sample of hospital cardiac
      care units; assess association of these practices with processes of care,
      readmissions, and mortality for patients with acute myocardial infarction (AMI);
      and suggest specific directions for the testing and dissemination of health care
      management approaches. DESIGN: We adapted an approach used to measure management
      and organizational practices in manufacturing to collect management data on
      cardiac units. We scored performance in 18 practices using the following 4
      dimensions: standardizing care, tracking of key performance indicators, setting
      targets, and incentivizing employees. We used multivariate analyses to assess the
      relationship of management practices with process-of-care measures, 30-day risk
      adjusted mortality, and 30-day readmissions for acute myocardial infarction
      (AMI). SETTING: Cardiac units in US hospitals. PARTICIPANTS: Five hundred ninety
      seven cardiac units, representing 51.5% of hospitals with interventional cardiac
      catheterization laboratories and at least 25 annual AMI discharges. MAIN OUTCOME
      MEASURES: Process-of-care measures, 30-day risk-adjusted mortality, and 30-day
      readmissions for AMI. RESULTS: We found a wide distribution in management
      practices, with fewer than 20% of hospitals scoring a 4 or a 5 (best practice) on
      more than 9 measures. In multivariate analyses, management practices were
      significantly correlated with mortality (P = .01) and 6 of 6 process measures (P
      < .05). No statistically significant association was found between management and
      30-day readmissions. CONCLUSIONS AND RELEVANCE: The use of management practices
      adopted from manufacturing sectors is associated with higher process-of-care
      measures and lower 30-day AMI mortality. Given the wide differences in management
      practices across hospitals, dissemination of these practices may be beneficial in
      achieving high-quality outcomes.

PMID- 23552987
TI  - Re: "Self-reported sleep duration, sleep quality, and breast cancer risk in a
      population-based case-control study".

PMID- 23552989
TI  - Positive association between perfluoroalkyl chemicals and hyperuricemia in
      children.
AB  - Hyperuricemia in children is associated with increased risk of high blood
      pressure, metabolic syndrome, and future cardiovascular disease. Serum
      perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) levels have
      been shown to be positively associated with hyperuricemia in adults, but the
      association in children remains unexplored. We therefore examined the association
      between serum PFOA and PFOS levels and hyperuricemia in a representative sample
      of US children. A cross-sectional study was performed on 1,772 participants <=18
      years of age from the National Health and Nutrition Examination Survey 1999-2000
      and 2003-2008. The main outcome of interest was hyperuricemia, defined as serum
      uric acid levels >=6 mg/dL. We found that serum levels of PFOA and PFOS were
      positively associated with hyperuricemia, independent of age, sex,
      race/ethnicity, body mass index, annual household income, physical activity,
      serum total cholesterol, and serum cotinine levels. Compared with subjects in
      quartile 1 (referent), subjects in quartile 4 had multivariable-adjusted odds
      ratios for hyperuricemia of 1.62 (95% confidence interval: 1.10, 2.37) for PFOA
      and 1.65 (95% confidence interval: 1.10, 2.49) for PFOS. Our findings indicate
      that serum perfluoroalkyl chemical levels are significantly associated with
      hyperuricemia in children even at the lower "background" exposure levels of the
      US general population.

PMID- 23552988
TI  - Association of functional polymorphism rs2231142 (Q141K) in the ABCG2 gene with
      serum uric acid and gout in 4 US populations: the PAGE Study.
AB  - A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette,
      subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum
      uric acid levels and gout in Asians, Europeans, and European and African
      Americans; however, less is known about these associations in other populations.
      Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans,
      3,849 Mexican Americans, and 3,550 American Indians in the Population
      Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142
      was significantly associated with serum uric acid levels (P = 2.37 * 10(-67), P =
      3.98 * 10(-5), P = 6.97 * 10(-9), and P = 5.33 * 10(-4) in European Americans,
      African Americans, Mexican Americans, and American Indians, respectively) and
      gout (P = 2.83 * 10(-10), P = 0.01, and P = 0.01 in European Americans, African
      Americans, and Mexican Americans, respectively). Overall, the T allele was
      associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 * 10(
      80)) and a 1.75-fold increase in the odds of gout (P = 1.09 * 10(-12)). The
      association between rs2231142 and serum uric acid was significantly stronger in
      men, postmenopausal women, and hormone therapy users compared with their
      counterparts. The association with gout was also significantly stronger in men
      than in women. These results highlight a possible role of sex hormones in the
      regulation of ABCG2 urate transporter and its potential implications for the
      prevention, diagnosis, and treatment of hyperuricemia and gout. 

PMID- 23552990
TI  - Adaptive reconfiguration of the human NK-cell compartment in response to
      cytomegalovirus: a different perspective of the host-pathogen interaction.
AB  - As discussed in this review, human cytomegalovirus (HCMV) infection in healthy
      individuals is associated with a variable and persistent increase of NK cells
      expressing the CD94/NKG2C activating receptor. The expansion of NKG2C(+) NK cells
      reported in other infectious diseases is systematically associated with HCMV co
      infection. The functionally mature NKG2C(bright) NK-cell subset expanding in
      HCMV(+) individuals displays inhibitory Ig-like receptors (KIR and LILRB1)
      specific for self HLA class I, and low levels of NKp46 and NKp30 activating
      receptors. Such reconfiguration of the NK-cell compartment appears particularly
      marked in immunocompromised patients and in children with symptomatic congenital
      infection, thus suggesting that its magnitude may be inversely related with the
      efficiency of the T-cell-mediated response. This effect of HCMV infection is
      reminiscent of the pattern of response of murine Ly49H(+) NK cells against murine
      CMV (MCMV), and it has been hypothesized that a cognate interaction of the
      CD94/NKG2C receptor with HCMV-infected cells may drive the expansion of the
      corresponding NK-cell subset. Yet, the precise role of NKG2C(+) cells in the
      control of HCMV infection, the molecular mechanisms underlying the NK-cell
      compartment redistribution, as well as its putative influence in the response to
      other pathogens and tumors remain open issues.

PMID- 23552991
TI  - Expression and biological properties of a novel methionine sulfoxide reductase A
      in tobacco (Nicotiana tabacum).
AB  - Methionine (Met) residues in proteins/peptides are extremely susceptible to
      oxidation mediated by reactive oxygen species, resulting in the formation of
      methionine sulfoxide, which could be inversely reduced back to Met by methionine
      sulfoxide reductase (MSR). In the present study, an A-type MSR gene, termed
      NtMSRA4, was isolated from tobacco (Nicotiana tabacum). Sequence analysis of
      NtMSRA4 amino acid sequence indicated that the gene, encoded a polypeptide with a
      molecular weight of 21 kDa, possessed the highly conserved motif, 'GCFWG' in the
      N-terminus and 'KGCNDPIRCY' motif in the C-terminus respectively. Substrate
      specific analysis revealed that recombinant NtMSRA4 protein could reduce
      specifically S-isomer of Dabsyl-MetSO to Dabsyl-Met in vitro using dithiothreitol
      as an electron donor. Enzymatic properties analysis showed that the temperature
      of 42  degrees C and pH 9.0 were optimum for NtMSRA4 activity. The K m and K cat
      values of NtMSRA4 were determined to be 40.04 MUM and 0.048 S(-1) in the
      thioredoxin dependent reduction system. Overexpression of NtMSRA4 in E. coli
      cells enhanced resistance to H2O2 toxicity. Subcellular localization result
      showed that NtMSRA4 was located in the chloroplast. The expression level of
      NtMSRA4 was affected differently after exposure to various abiotic stresses.

PMID- 23552993
TI  - Changes in television viewing and computers/videogames use among high school
      students in Southern Brazil between 2001 and 2011.
AB  - OBJECTIVES: To compare the prevalence of television (TV) watching and of
      computer/videogame use among high school students (15-19 years) from Southern
      Brazil between 2001 and 2011 and to identify associated socio-demographic
      factors. METHODS: Panel studies were conducted with high school students in the
      state of Santa Catarina, Brazil, in 2001 (n = 5,028) and 2011 (n = 6,529). TV
      watching and computer/videogame use were collected using questionnaires. RESULTS:
      Prevalence of >=2 h/day of TV watching dropped from 76.8 to 61.5 % and >=2 h/day
      of computer/videogame use increased from 37.9 to 60.6 %. In both surveys, those
      aged 15-16 and those who did not work had higher likelihoods of being exposed to
      >=2 h/day of TV watching. Boys, those with higher family income, and those who
      were living in urban areas had higher likelihoods of >=2 h/day of
      computer/videogame use. Older age, studying at night and not working were
      protective factors to these behaviors. CONCLUSIONS: After a decade, there was a
      decrease in the prevalence of TV viewing and an increase in computer/videogame
      use. Socio-demographic factors were differently associated with these behaviors.

PMID- 23552992
TI  - Biomarker testing for ovarian cancer: clinical utility of multiplex assays.
AB  - The improved detection of ovarian cancer at the earliest stages of development
      would confer a significant benefit in the therapeutic efficacy and overall
      survival associated with this devastating disease. The inadequate performance of
      currently used imaging modalities and the CA 125 biomarker test have precluded
      the establishment of screening programs and hindered the development of
      diagnostic tests for ovarian cancer. Two recently completed large clinical trials
      of ovarian cancer screening have reported findings of mixed impact, further
      clouding the issue. Considerable effort has been applied to the development of
      multiplexed biomarker-based tests and the most recent advances are discussed
      here. Within the clinical setting of pelvic mass differential diagnosis and
      triage, several significant advancements have been achieved recently, including
      the US Food and Drug Administration-approved Risk of Ovarian Malignancy Algorithm
      and OVA1 tests. The development and evaluation of those tests are described in
      this review. Thus while effective routine screening for ovarian cancer remains a
      lofty goal, advancement within the clinical management of pelvic mass diagnoses
      appears to be near at hand.

PMID- 23552994
TI  - Effects of bed bug saliva on human skin.

PMID- 23552996
TI  - Following and intercepting scribbles: interactions between eye and hand control.
AB  - The smooth pursuit eye movement system appears to be importantly engaged during
      the planning and execution of interceptive hand movements. The present study
      sought to probe the interaction between eye and hand control systems by examining
      their responses during an interception task that included target speed
      perturbations. On 2/3 of trials, the target increased or decreased speed at
      various times, ranging from about 300 ms before to 150 ms after the onset of a
      finger movement directed to intercept the target and was triggered by a GO
      signal. Additionally, the same 2D sum-of-sines target trajectories were followed
      with the eyes without interception. The smooth pursuit system responded more
      quickly if the target speed perturbation occurred earlier during the reaction
      time (i.e., near the time of the GO signal). Similarly, the finger movement began
      more quickly if target speed was increased earlier during the reaction time. For
      early perturbation conditions, the initial direction of the finger movement
      matched the predicted target intercept using the new target speed. For
      perturbations occurring after finger movement, onset initial direction of finger
      movement did not match target interception such that the finger path began to
      curve toward the perturbed target after about 150-200 ms. The results support the
      idea of an active process of visual target path extrapolation simultaneously used
      to guide both the eye and hand.

PMID- 23552997
TI  - The vestibular system does not modulate fusimotor drive to muscle spindles in
      contracting leg muscles of seated subjects.
AB  - We previously showed that sinusoidal galvanic vestibular stimulation (GVS) does
      not modulate the firing of spontaneously active muscle spindles in relaxed human
      leg muscles. However, given that there is little, if any, fusimotor drive to
      relaxed human muscles, we tested the hypothesis that vestibular modulation of
      muscle spindles becomes apparent during volitional contractions at levels that
      engage the fusimotor system. Unitary recordings were made from 28 muscle spindle
      afferents via tungsten microelectrodes inserted percutaneously into the common
      peroneal nerve of seated awake human subjects. Twenty-one of the spindle
      afferents were spontaneously active at rest and each increased its firing rate
      during a weak static contraction; seven were silent at rest and were recruited
      during the contraction. Sinusoidal bipolar binaural galvanic vestibular
      stimulation (+/-2 mA, 100 cycles) was applied to the mastoid processes at 0.8 Hz.
      This continuous stimulation produced a sustained illusion of "rocking in a boat"
      or "swinging in a hammock" but no entrainment of EMG. Despite these robust
      vestibular illusions, none of the fusimotor-driven muscle spindles exhibited
      phase-locked modulation of firing during sinusoidal GVS. We conclude that this
      dynamic vestibular input was not sufficient to modulate the firing of fusimotor
      neurones recruited during a voluntary steady-state contraction, arguing against a
      significant role of the vestibular system in adjusting the sensitivity of muscle
      spindles via fusimotor neurones.

PMID- 23552998
TI  - Identification of soluble 14-3-3? as a novel subchondral bone mediator involved
      in cartilage degradation in osteoarthritis.
AB  - OBJECTIVE: Mechanical stress plays an important role in cartilage degradation and
      subchondral bone remodeling in osteoarthritis (OA). The remodeling of the
      subchondral bone could initiate cartilage loss in OA through the interplay of
      bone and cartilage. The aim of this study was to identify soluble mediators
      released by loaded osteoblasts/osteocytes that could induce the release of
      catabolic factors by chondrocytes. METHODS: Murine osteoblasts/osteocytes were
      subjected to cyclic compression, and then conditioned medium from either
      compressed (CCM) or uncompressed (UCM) cells was used to stimulate mouse
      chondrocytes. Chondrocyte expression of matrix metalloproteinase 3 (MMP-3), MMP
      13, type II collagen, and aggrecan was assessed by reverse transcription
      polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent
      assay. Soluble mediators released by compressed osteoblasts/osteocytes were
      identified using iTRAQ (isobaric tags for relative and absolute quantification),
      a differential secretome analysis. Subchondral bone and cartilage samples were
      isolated from OA patients, and culture medium conditioned with OA subchondral
      bone or cartilage was used to stimulate human chondrocytes. RESULTS: Stimulation
      of mouse chondrocytes with CCM strongly induced the messenger RNA (mRNA)
      expression and protein release of MMP-3 and MMP-13 and inhibited the mRNA
      expression of type II collagen and aggrecan. Differential secretome analysis
      revealed that 10 proteins were up-regulated in compressed osteoblasts/osteocytes.
      Among them, soluble 14-3-3? (s14-3-3?) dose-dependently induced the release of
      catabolic factors by chondrocytes, mimicking the effects of cell compression.
      Addition of a 14-3-3? blocking antibody greatly attenuated the CCM-mediated
      induction of MMP-3 and MMP-13 expression. Furthermore, in human OA subchondral
      bone, s14-3-3? was strongly released, and in cultures of human OA chondrocytes,
      s14-3-3? stimulated MMP-3 expression. CONCLUSION: The results of this study
      identify s14-3-3? as a novel soluble mediator critical in the communication
      between subchondral bone and cartilage in OA. Thus, s14-3-3? may be a potential
      target for future therapeutic or prognostic applications in OA.

PMID- 23553000
TI  - Cancer caregivers information needs and resource preferences.
AB  - This study sought to characterize the need for information about personal
      psychosocial care, providing direct care, and managing care among cancer
      caregivers and to explore preferred resources for caregiving information. Data
      come from cross-sectional telephone interviews of 1,247 family caregivers, which
      included 104 cancer caregivers. A majority of cancer caregivers expressed one or
      more information need for each of the three content categories. Four out of ten
      caregivers expressed needing information about managing physical and emotional
      stress. A significantly higher percentage of male caregivers reported needing
      more information pertinent to providing direct care than females. Heightened
      objective burden was significantly associated with caregivers preferring to
      receive information from health professionals than informal sources (e.g.,
      Internet), while the opposite was found among caregivers with lower objective
      burden. These findings suggest that specific types of information and resources
      may be most relevant to specific subgroups of cancer caregivers.

PMID- 23553001
TI  - Human-associated methicillin-resistant Staphylococcus aureus from a subtropical
      recreational marine beach.
AB  - Reports of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA)
      detected in marine environments have occurred since the early 1990 s. This
      investigation sought to isolate and characterize S. aureus from marine waters and
      sand at a subtropical recreational beach, with and without bathers present, in
      order to investigate possible sources and to identify the risks to bathers of
      exposure to these organisms. During 40 days over 17 months, 1,001 water and 36
      intertidal sand samples were collected by either bathers or investigators at a
      subtropical recreational beach. Methicillin-sensitive S. aureus (MSSA) and MRSA
      were isolated and identified using selective growth media and an organism
      specific molecular marker. Antimicrobial susceptibility, staphylococcal cassette
      chromosome mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) pattern,
      multi-locus sequence type (MLST), and staphylococcal protein A (spa) type were
      characterized for all MRSA. S. aureus was isolated from 248 (37 %) bather nearby
      water samples at a concentration range of <2-780 colony forming units per ml, 102
      (31 %) ambient water samples at a concentration range of <2-260 colony forming
      units per ml, and 9 (25 %) sand samples. Within the sand environment, S. aureus
      was isolated more often from above the intertidal zone than from intermittently
      wet or inundated sand. A total of 1334 MSSA were isolated from 37 sampling days
      and 22 MRSA were isolated from ten sampling days. Seventeen of the 22 MRSA were
      identified by PFGE as the community-associated MRSA USA300. MRSA isolates were
      all SCCmec type IVa, encompassed five spa types (t008, t064, t622, t688, and
      t723), two MLST types (ST8 and ST5), and 21 of 22 isolates carried the genes for
      Panton-Valentine leukocidin. There was a correlation (r = 0.45; p = 0.05) between
      the daily average number of bathers and S. aureus in the water; however, no
      association between exposure to S. aureus in these waters and reported illness
      was found. This report supports the concept that humans are a potential direct
      source for S. aureus in marine waters.

PMID- 23553002
TI  - "Eco-omics": a review of the application of genomics, transcriptomics, and
      proteomics for the study of the ecology of harmful algae.
AB  - The implementation of molecular techniques has been widely adopted throughout the
      life sciences except in the marine sciences. The latter trend is quickly being
      reversed as even more cutting-edge molecular platforms, referred to collectively
      as 'omics-related technologies, are being used in a number of laboratories that
      study various aspects of life in the marine environment. This review provides a
      brief overview of just a few representative studies that have used genomics,
      transcriptomics, or proteomics approaches to deepen our understanding,
      specifically, about the underlying molecular biology of harmful algae. The
      examples of the studies described here are particularly relevant in showing how
      the information gleaned from these technologies can uncover the genetic capacity
      of harmful algal bloom-forming species, can generate new hypotheses about
      mechanistic relationships that bridge gene-environment interactions, and can
      impinge on our understanding surrounding the ecology of these organisms.

PMID- 23553003
TI  - Church-based social support, functional disability, and change in personal
      control over time.
AB  - The purpose of this study is to see whether measures of church-based and secular
      social support offset the effects of functional disability on change in feelings
      of personal control over time. Survey data were obtained from Wave 2 and Wave 3
      of a nationwide sample of older adults (N = 583). The findings suggest that
      spiritual support from fellow church members offsets the effects of functional
      disability on change in feelings of personal control over time. In contrast,
      neither emotional support from fellow church members nor emotional support from
      secular social network members exerted a similar effect. 

PMID- 23553004
TI  - Biodegradability and mesophilic co-digestion of municipal sludge and scum.
AB  - The objective of this study is to investigate and optimize the co-digestion of
      scum with thickened waste activated sludge (TWAS) and primary sludge (PS)
      undergoing mesophilic anaerobic digestion. The effect of scum loading on the co
      digestion of PS, TWAS and scum has shown to have a significant impact on the
      ultimate cumulative biogas production and on the specific biogas production
      between 20 and 40 days of digestion, while the effects of the scum holding time
      within the scum concentrator and temperature of the scum concentrator did not
      demonstrate a significant effect on the ultimate or specific biogas production.
      The study demonstrates that care must be taken to avoid inhibitory effects and
      potential souring of digesters due to scum overloading and specifically scum
      overloading in combination with long holding times of scum within the scum
      concentrator at elevated temperatures. 

PMID- 23553005
TI  - Author reply: To PMID 22986377.

PMID- 23553006
TI  - ACP Journal Club. Review: SSRIs somewhat improve dependence and disability after
      stroke.

PMID- 23553007
TI  - Longitudinal occlusal changes during the primary dentition and during the passage
      from primary dentition to mixed dentition among a group of Turkish children.
AB  - AIM: To determine the changes in the molar and canine relationships in transition
      from the primary to the mixed dentition in 98 subjects selected among Turkish
      children living in the Erzurum city centre. METHODS: This study is based on a 3
      year follow-up of 98 children (46 girls, 52 boys) between the ages of 4 and 6
      years at the start of the study. The survey focused on the investigation of the
      changes that appeared in the occlusal relationships in the primary dentition and
      in the transition to the mixed dentition according to gender and age. RESULTS:
      The findings indicated that 73.6 % of the 98 cases evaluated in the primary
      dentition developed a Class I molar relationship, and 26.4 % developed a Class II
      molar relationship. As 64.3 % FTP, 22.4 % DS, and 13.3 % MS molar occlusal
      relationships were evaluated at baseline; 22.4 % FTP, 11.2 % DS, and 66.3 % MS
      molar occlusal relationships were evaluated at the end of the third year. While
      75.5 % Class I, 11.2 % Class II, and 13.3 % Class III primary canine occlusal
      relationships were evaluated at baseline; 53.1 % Class I, 5.1 % Class II, and
      41.8 % Class III primary canine occlusal relationships were evaluated at the end
      of the third year. With increased age, a statistically significant difference (p
      < 0.001) was found in flush terminal plane, mesial step, and primary canine
      occlusal relationships and no statistically significant difference (p > 0.05) was
      found in distal step relationships. CONCLUSION: Malocclusions observed in the
      primary dentition are signs of malocclusions in the permanent dentition.

PMID- 23553008
TI  - Bullous pemphigoid.

PMID- 23553011
TI  - Improving prescribing of antibiotics in long-term care: resistant to change?

PMID- 23553009
TI  - Secondary hyperpigmentation during interferon alfa treatment for chronic
      hepatitis C virus infection.
AB  - IMPORTANCE: Interferon alfa remains the central treatment for chronic hepatitis C
      virus (HCV) infection. Cases of cutaneous and mucous hyperpigmentations during
      interferon alfa treatment have been reported, but they are considered rare
      adverse effects. OBJECTIVE: To study the clinical presentation and frequency of
      hyperpigmentation in patients receiving interferon alfa treatment for chronic HCV
      infection. DESIGN: Prospective, descriptive clinical trial. SETTING: Monocentric
      study performed in the Departments of Hepatology and Dermatology of the
      University Hospital of Nice, Nice, France. PARTICIPANTS: Consecutive patients
      treated with pegylated interferon alfa-2b and ribavirin for chronic HCV
      infection. MAIN OUTCOME MEASURES: Demographic data and medical history were
      noted. A systematic clinical and dermoscopic examination of skin, nails, and
      mucous membranes was performed, and skin biopsies were performed if needed.
      RESULTS: Of 77 patients who were included, 16 (21%) presented with
      hyperpigmentation. Hyperpigmentation of the oral mucous membrane, acquired
      longitudinal melononychia, and hyperpigmentation of the face were each observed
      in 7 patients (9%). All patients with hyperpigmentation of the skin had skin type
      III or IV and worked outside without sun protection. The intensity of
      pigmentation was reported to decrease progressively when interferon treatment was
      discontinued. Most patients with hyperpigmentation of the oral mucosa also had
      melanonychia. However, patients with hyperpigmentation of the skin did not have
      mucosal or nail involvement, suggesting 2 distinct mechanisms. CONCLUSIONS AND
      RELEVANCE: Secondary hyperpigmentation during interferon alfa treatment occurs as
      an adverse event in 21% of patients, especially in those with dark skin types who
      have unprotected sun exposure. Physicians should be aware of the adverse effects
      of interferon treatment and advise patients in the use of sun protection,
      especially patients with darker skin types.

PMID- 23553012
TI  - [Physicians' Loci communes. Forms and Functions of Medical Commonplacing in the
      Sixteenth and Seventeenth Centuries].

PMID- 23553015
TI  - Livedo reticularis and skin necrosis due to hyaluronic acid embolism.

PMID- 23553016
TI  - The effect of carvacrol on healthy neurons and N2a cancer cells: some
      biochemical, anticancerogenicity and genotoxicity studies.
AB  - Carvacrol (CVC) is a phenolic monoterpene present in many essential oils of
      medicinal and aromatic plants and has attracted attention because of its
      beneficial biological activities. To date, although various biological activities
      of CVC have been demonstrated, its neurotoxicity on cultured primary rat neurons
      and N2a neuroblastoma cells has never been explored. Therefore, in this present
      study, we aimed to describe in vitro antiproliferative and/or cytotoxic
      properties (by 3-(4,5 dimetylthiazol -2-yl)-2,5 diphenlytetrazolium bromide (MTT)
      test), genotoxic damage potentials (by single cell gel electrophoresis (SCGE) or
      Comet assay) and antioxidant activities (by total antioxidant capacity (TAC) and
      total oxidative stress (TOS) analysis) of CVC in vitro. Dose (0-400 mg/L)
      dependent effects of CVC were tested on both cultured primary rat neurons and N2a
      neuroblastoma cells. Statistical analysis of MTT assay results indicated
      significant (p < 0.05) decreases of cell proliferation rates in both cell types
      treated with CVC at 200 and 400 mg/L. On the other hand, the mean values of the
      total scores of cells showing DNA damage (for comet assay) was not found
      significantly different from the control values for both cells (p > 0.05). In
      addition, our results indicated that 10, 25 and 50 mg/L of CVC treatment caused
      increases of TAC levels in cultured primary rat neurons but not in the N2a cell
      line. However, CVC treatments led to increases of TOS levels in cultured primary
      rat neurons at only 400 mg/L while they led to increases of TOS levels in N2a
      neuroblastoma cells at 200 and 400 mg/L. The present findings demonstrated that
      CVC could be a source of antioxidant and chemopreventive activities to be studied
      on cancer diseases. 

PMID- 23553017
TI  - Lineage depletion of stromal vascular fractions isolated from human adipose
      tissue: a novel approach towards cell enrichment technology.
AB  - The therapeutic rationale for tissue repair and regeneration using stem cells is
      at its infancy and needs advancement in understanding the role of individual
      component's innate capability. As stem cells of adipose tissue reside in a more
      heterogeneous population of stromal vascular fractions, cell separation or
      sorting becomes an eminent step towards revealing their unique properties. This
      study elucidates the comparative efficacy of lineage depleted adipose derived
      stromal vascular fraction (SVF) and their innate ability using magnetic activated
      cell sorter (MACS). To this end, isolated SVF from human adipose tissue was
      lineage depleted according to the manufacturer's instructions using specific
      antibody cocktail through MACS. The enriched lineage negative (lin-) and lineage
      positive (lin+) cell fractions were cultured, phenotypically characterized for
      the panel of cell surface markers using flowcytometry and subjected to
      osteoblastic and adipogenic differentiation. The expression profile obtained for
      lin- cells was CD34-/CD45-/HLADR-/CD49d-/CD140b-/CD31
      /CD90+/CD105+/CD73+/CD54+/CD166+/CD117- when compared to Lin+ cells expressing
      CD34+/CD45+/HLADR-/CD49d-/CD140b+/CD31-/CD90+/CD105+/CD73+/CD54+/CD166+/CD117+
      (CD-cluster of differentiation). These results, thus, advances our understanding
      on the inherent property of the individual cell population. Furthermore, both the
      fractions exhibited mesodermal lineage differentiation capacity. To conclude,
      this research pursuit rationalized the regenerative therapeutic applicability of
      both lin- and lin+ cultures of human adipose tissue for disorders of mesodermal,
      haematological and vascular origin. 

PMID- 23553018
TI  - Effects of long-term serial cell passaging on cell spreading, migration, and cell
      surface ultrastructures of cultured vascular endothelial cells.
AB  - The effects of serial cell passaging on cell spreading, migration, and cell
      surface ultrastructures have been less investigated directly. This study
      evaluated the effects of long-term serial cell passaging (totally 35 passages) on
      cultured human umbilical vein endothelial cells which were pre-stored at -80 
      degrees C as usual. Percentage- and spread area-based spreading assays,
      measurements of fluorescently labeled actin filaments, migration assay, and
      measurements of cell-surface roughness were performed and quantitatively analyzed
      by confocal microscopy or atomic force microscopy. We found that the abilities of
      cell spreading and migration first increased at early passages and then decreased
      after passage 15, in agreement with the changes in average length of actin
      filaments. Recovery from cold storage and effects of cell passaging were
      potentially responsible for the increases and decreases of the values,
      respectively. In contrast, the average roughness of cell surfaces (particularly
      the nucleus-surrounding region) first dropped at early passages and then rose
      after passage 15, which might be caused by cold storage- and cell passaging
      induced endothelial microparticles. Our data will provide important information
      for understanding serial cell passaging and implies that for pre-stored adherent
      cells at -80  degrees C cell passages 5-10 are optimal for in vitro studies. 

PMID- 23553020
TI  - [Rheumatology update].

PMID- 23553019
TI  - Selection of appropriate isolation method based on morphology of blastocyst for
      efficient derivation of buffalo embryonic stem cells.
AB  - The efficiency of embryonic stem cell (ESC) derivation from all species except
      for rodents and primates is very low. There are however, multiple interests in
      obtaining pluripotent cells from these animals with main expectations in the
      fields of transgenesis, cloning, regenerative medicine and tissue engineering.
      Researches are being carried out in laboratories throughout the world to increase
      the efficiency of ESC isolation for their downstream applications. Thus, the
      present study was undertaken to study the effect of different isolation methods
      based on the morphology of blastocyst for efficient derivation of buffalo ESCs.
      Embryos were produced in vitro through the procedures of maturation,
      fertilization and culture. Hatched blastocysts or isolated inner cell masses
      (ICMs) were seeded on mitomycin-C inactivated buffalo fetal fibroblast monolayer
      for the development of ESC colonies. The ESCs were analyzed for alkaline
      phosphatase activity, expression of pluripotency markers and karyotypic
      stability. Primary ESC colonies were obtained after 2-5 days of seeding hatched
      blastocysts or isolated ICMs on mitomycin-C inactivated feeder layer.
      Mechanically isolated ICMs attached and formed primary cell colonies more
      efficiently than ICMs isolated enzymatically. For derivation of ESCs from poorly
      defined ICMs intact hatched blastocyst culture was the most successful method.
      Results of this study implied that although ESCs can be obtained using all three
      methods used in this study, efficiency varies depending upon the morphology of
      blastocyst and isolation method used. So, appropriate isolation method must be
      selected depending on the quality of blastocyst for efficient derivation of ESCs.

PMID- 23553021
TI  - [Interstitial lung disease in polymyositis/dermatomyositis].
AB  - Comprehensive screening can disclose evidence of interstitial lung disease (ILD)
      in about 40 % of patients with polymyositis/dermatomyositis (PM/DM). In most
      cases this is a non-specific interstitial pneumonia, a histopathological type
      characterized by a substantial initial inflammatory component. Autoantibody
      testing, spirometry, including the measurement of the the CO diffusion capacity
      and high-resolution computed tomography (HRCT) are central to making the
      diagnosis during the early inflammatory stages of ILD. This article outlines the
      use of clinical, HRCT and bronchoalveolar lavage (BAL) findings for
      prognostication and gives an overview of current treatment options.

PMID- 23553022
TI  - [Metabolic and mitochondrial myopathies].
AB  - Metabolic myopathies include a broad group of diseases involving inherited enzyme
      defects in the various metabolic pathways and skeletal musculature. They show an
      extensive phenotypic variability of symptoms and different ages of manifestation.
      Symptoms often included intolerance to duress or permanent paresis. Some forms of
      metabolic myopathy, in particular mitochondriopathy, are associated with
      multsystemic organ participation. The diagnostics must be adjusted to individual
      cases and carried out in stages. Primary investigations should include blood
      parameters (e.g. creatine kinase measurement, muscle load tests and determination
      of the acylcarnitine spectrum) and a second step includes muscle biopsy for
      histological and enzyme investigations and special molecular genetic tests
      although the causative enzyme defect cannot be clarified in every case. On the
      other hand by means of a thorough investigation it is particularly important in
      patients with load intolerance to differentiate between other causes, in
      particular psychosomatic diseases. If this is not done there is a danger of
      classifying the symptoms of a metabolic myopathy as a somatoform disorder.
      Therapy is mostly symptom-oriented as Pompe disease is the only one which can be
      treated with enzyme replacement therapy.

PMID- 23553023
TI  - [Fever of unknown origin].
AB  - Fever of unknown origin (FUO) is defined as sustained unexplained fever despite
      intensive diagnostic evaluation and represents a particular diagnostic challenge.
      It can be classified into different categories, e.g. classical, nosocomial,
      neutropenic and HIV-associated FUO, which is based on the patient-specific
      clinical and immunological situation. Infections, malignant diseases and non
      infectious inflammatory diseases have to be considered as the most important
      causes of FUO; however, no definitive diagnosis can be established in a
      substantial number of FUO patients despite an extensive diagnostic work-up. The
      present review focuses on the important diagnostic aspects as well as therapeutic
      options in FUO patients.

PMID- 23553027
TI  - Effects of Rab27a on proliferation, invasion, and anti-apoptosis in human glioma
      cell.
AB  - This study aims to investigate the relationship between Rab27a and the
      characteristics of glioma cell U251 such as proliferation, apoptosis, and
      invasion and to provide an experimental basis for future therapy in human glioma.
      Recombinant plasmid of pcDNA3.1-Rab27a was constructed and transfected into U251
      cells with the help of LipofectamineTM2000. The expression of Rab27a was detected
      by Western blot. Cell viability, cell cycle, cell apoptosis, and cell migration
      were analyzed, respectively, by (3-(4,5)-dimethylthi-azol-2-yl)-2,5
      diphenytetrazolium bromide (MTT) assay, flow cytometry, and Transwell invasion
      chamber methods. Meanwhile, the effect of Rab27a on secretion of cathepsin D in
      U251 cells was also examined. With the help of luciferase reporter assay system,
      the relationship between miR-124 and gene Rab27a expression was explored. Western
      blot showed that the expression of Rab27a was significantly increased in pcDNA3.1
      Rab27a transfection group (p < 0.01) and that was significantly decreased in
      Rab27a-shRNA transfection group (p < 0.01) compared with control group. MTT
      assay, flow cytometry, and Transwell invasion chamber experiment indicated that
      cell viability (p < 0.01), proliferation index (p < 0.05), and invasion ability
      (p < 0.01) were improved significantly in pcDNA3.1-Rab27a transfection group
      compared with control group and that cell viability (p < 0.01), proliferation
      index (p < 0.05), and invasion ability (p < 0.01) were reduced markedly in Rab27a
      shRNA transfection group compared with control group. The apoptosis analysis by
      flow cytometry demonstrated that the ratio of apoptosis in pcDNA3.1-Rab27a
      transfection group was significantly lower than that in control group (p < 0.05)
      and the ratio was notably higher in Rab27a-shRNAtransfection group than that in
      the control group. Cathepsin D activity assay indicated that the release of
      cathepsin D was enhanced in pcDNA3.1-Rab27a transfection group compared to that
      in the control group (p < 0.05). Rab27a could increase the glioma cell ability,
      promote proliferation and invasion, and suppress cell apoptosis. The above-stated
      effects of Rab27a possibly were exerted by increasing the secretion of cathepsin
      D and regulated by miR-124. In addition, the inhibition of expression of Rab27a
      perhaps benefited the therapy for glioma patients.

PMID- 23553028
TI  - HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta
      analysis.
AB  - The HFE gene has been suggested to play an important role in the pathogenesis of
      colorectal cancer. However, the results have been conflicting. In this study, we
      performed a meta-analysis to clarify the association of HFE gene C282Y variant
      with colorectal cancer. PubMed and Embase were retrieved to identify the
      potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI)
      was calculated using fixed- or random-effects model. A total of eight papers
      including nine studies (7,588 colorectal cancer cases and 81,571 controls) for
      HFE gene C282Y variant were included in the meta-analysis. The result indicated
      that HFE gene C282Y variant was significantly associated with colorectal cancer
      under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of
      between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis
      by number of cases suggested the effect was significant in studies with more than
      500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in
      studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %,
      p = 0.622). The current meta-analysis supported the positive association of HFE
      gene C282Y variant with colorectal cancer. Further large-scale studies with the
      consideration for gene-gene/gene-environment interactions should be conducted to
      investigate the association.

PMID- 23553029
TI  - Overexpression of ECRG4 enhances chemosensitivity to 5-fluorouracil in the human
      gastric cancer SGC-7901 cell line.
AB  - The aim of this study was to examine the effects of esophageal cancer-related
      gene 4 (ECRG4) expression levels on chemotherapeutic sensitivity of gastric
      cancer cells. A SGC-7901 cell system with tetracycline-inducible ECRG4 expression
      (SGC-7901/ECRG4) was successfully established. ECRG4 mRNA and protein expression
      levels were detected using quantitative reverse transcription polymerase chain
      reaction and Western blotting, respectively. Chemosensitivity to 5-fluorouracil
      (5-FU) was examined by cell proliferation assay and cell apoptosis assay. ECRG4
      mRNA and protein expression levels were significantly upregulated in SGC
      7901/ECRG4 cells induced with tetracycline. Compared with control cells, the
      growth inhibition rate of cells with ECRG4 overexpression was significantly
      increased when treated with 5-FU. Treatment with 5 MUmol/l 5-FU resulted in 15.2
      % apoptotic cells, whereas such treatment after overexpression of ECRG4 resulted
      in 44.5 % apoptotic cells. In conclusion, overexpression of ECRG4 enhanced the
      chemosensitivity of gastric cancer SGC-7901 cells to 5-FU through induction of
      apoptosis.

PMID- 23553030
TI  - Expanding horizons of shikimic acid. Recent progresses in production and its
      endless frontiers in application and market trends.
AB  - Shikimic acid is an industrially important chiral compound used as a key
      ingredient in formulation of drug Oseltamivir phosphate (Tamiflu) for the
      treatment of swine/avian flu. The high cost and limited availability of shikimic
      acid isolated from plants has detained the use of this valuable building block of
      the drug. It is a versatile compound having many characteristic properties for
      many synthetic reactions particularly in pharmaceuticals and cosmetic industries.
      By virtue of being a natural product, the relevant biochemical pathway in
      microorganisms can be harnessed into fermentation processes to produce shikimic
      acid. This is an excellent alternative for the sustainable and efficient
      production of shikimic acid over the tedious and cumbersome process of plant
      based extraction methods. Various strategies of shikimic acid production are
      reviewed and an account of comparison of their challenges, promises and restraint
      is presented. Furthermore, present review attempts to focus on the market trend
      of shikimic acid due to its high demand with particular emphasis laid on the
      pandemics of swine flu. This review not only covers the recent advances in
      shikimic acid production but also highlights the versatile applications and its
      market scenario. The concluding remarks and its potential as a commercial bulk
      chemical are discussed in the light of current research.

PMID- 23553031
TI  - Effect of culture pH on recombinant antibody production by a new human cell line,
      F2N78, grown in suspension at 33.0  degrees C and 37.0  degrees C.
AB  - The human host cell line, F2N78, is a new somatic hybrid cell line designed for
      therapeutic antibody production. To verify its potential as a human host cell
      line, recombinant F2N78 cells that produce antibody against rabies virus (rF2N78)
      were cultivated at different culture pH (6.8, 7.0, 7.2, 7.4, and 7.6) and
      temperatures (33.0  degrees C and 37.0  degrees C). Regardless of the culture
      temperature, the highest specific growth rate was obtained at a pH of 7.0-7.4.
      Lowering the culture temperature from 37.0  degrees C to 33.0  degrees C
      suppressed cell growth while allowing maintenance of high cell viability for a
      longer period. However, it did not enhance antibody production because specific
      antibody productivity did not increase at 33.0  degrees C. The highest maximum
      antibody concentration was obtained at 37.0  degrees C and pH 6.8. The N-linked
      glycosylation of the antibody was affected by the culture pH rather than the
      temperature. Nevertheless, G1F was dominant and G2F occupied a larger portion
      than G0F in all culture conditions. Compared to the same antibody produced from
      recombinant CHO cells, the antibody produced from rF2N78 cells has more galactose
      capping and was more similar to human plasma IgG. Taken together, the results
      obtained here demonstrate the potential of F2N78 as an alternative human host
      cell line for therapeutic antibody production.

PMID- 23553032
TI  - Overexpression of stress-related genes enhances cell viability and velum
      formation in Sherry wine yeasts.
AB  - Flor formation and flor endurance have been related to ability by Saccharomyces
      cerevisiae flor yeasts to resist hostile conditions such as oxidative stress and
      the presence of acetaldehyde and ethanol. Ethanol and acetaldehyde toxicity give
      rise to formation of reactive oxygen species (ROS) and loss of cell viability.
      Superoxide dismutases Sod1p and Sod2p and other proteins such as Hsp12p are
      involved in oxidative stress tolerance. In this study, genes SOD1, SOD2, and
      HSP12 were overexpressed in flor yeast strains FJF206, FJF414 and B16. In the
      SOD1 and SOD2 transformant strains superoxide dismutases encoded by genes SOD1
      and SOD2 increased their specific activity considerably as a direct result of
      overexpression of genes SOD1 and SOD2, indirectly, catalase, glutathione
      reductase, and glutathione peroxidase activities increased too. The HSP12
      transformant strains showed higher levels of glutathione peroxidase and reductase
      activities. These transformant strains showed an increase in intracellular
      glutathione content, a reduction in peroxidized lipid concentration, and higher
      resistance to oxidative stress conditions. As a result, flor formation by these
      strains took place more rapidly than by their parental strains, velum being
      thicker and with higher percentages of viable cells. In addition, a slight
      decrease in ethanol and glycerol concentrations, and an increase in acetaldehyde
      were detected in wines matured under velum formed by transformant strains, as
      compared to their parental strains. In the industry, velum formed by transformant
      strains with increased viability may result in acceleration of both metabolism
      and wine aging, thus reducing time needed for wine maturation. 

PMID- 23553033
TI  - Core flooding tests to investigate the effects of IFT reduction and wettability
      alteration on oil recovery during MEOR process in an Iranian oil reservoir.
AB  - Microbial enhanced oil recovery (MEOR) refers to the process of using bacterial
      activities for more oil recovery from oil reservoirs mainly by interfacial
      tension reduction and wettability alteration mechanisms. Investigating the impact
      of these two mechanisms on enhanced oil recovery during MEOR process is the main
      objective of this work. Different analytical methods such as oil spreading and
      surface activity measurements were utilized to screen the biosurfactant-producing
      bacteria isolated from the brine of a specific oil reservoir located in the
      southwest of Iran. The isolates identified by 16S rDNA and biochemical analysis
      as Enterobacter cloacae (Persian Type Culture Collection (PTCC) 1798) and
      Enterobacter hormaechei (PTCC 1799) produce 1.53 g/l of biosurfactant. The
      produced biosurfactant caused substantial surface tension reduction of the growth
      medium and interfacial tension reduction between oil and brine to 31 and 3.2 mN/m
      from the original value of 72 and 29 mN/m, respectively. A novel set of core
      flooding tests, including in situ and ex situ scenarios, was designed to explore
      the potential of the isolated consortium as an agent for MEOR process. Besides,
      the individual effects of wettability alteration and IFT reduction on oil
      recovery efficiency by this process were investigated. The results show that the
      wettability alteration of the reservoir rock toward neutrally wet condition in
      the course of the adsorption of bacteria cells and biofilm formation are the
      dominant mechanisms on the improvement of oil recovery efficiency.

PMID- 23553034
TI  - Phospho-tyrosine phosphatase inhibitor Bpv(Hopic) enhances C2C12 myoblast
      migration in vitro. Requirement of PI3K/AKT and MAPK/ERK pathways.
AB  - Muscle progenitor cell migration is an important step in skeletal muscle
      myogenesis and regeneration. Migration is required for muscle precursors to reach
      the site of damage and for the alignment of myoblasts prior to their fusion,
      which ultimately contributes to muscle regeneration. Limited spreading and
      migration of donor myoblasts are reported problems of myoblast transfer therapy,
      a proposed therapeutic strategy for Duchenne Muscular Dystrophy, warranting
      further investigation into different approaches for improving the motility and
      homing of these cells. In this article, the effect of protein phospho-tyrosine
      phosphatase and PTEN inhibitor BpV(Hopic) on C2C12 myoblast migration and
      differentiation was investigated. Applying a wound healing migration model, it is
      reported that 1 MUM BpV(Hopic) is capable of enhancing the migration of C2C12
      myoblasts by approximately 40 % in the presence of myotube conditioned media,
      without significantly affecting their capacity to differentiate and fuse into
      multinucleated myotubes. Improved migration of myoblasts treated with 1 MUM
      BpV(Hopic) was associated with activation of PI3K/AKT and MAPK/ERK pathways,
      while their inhibition with either LY294002 or UO126, respectively, resulted in a
      reduction of C2C12 migration back to control levels. These results propose that
      bisperoxovanadium compounds may be considered as potential tools for enhancing
      the migration of myoblasts, while not reducing their differentiation capacity and
      underpin the importance of PI3K/AKT and MAPK/ERK signalling for the process of
      myogenic progenitor migration.

PMID- 23553035
TI  - Improving patient education with an eczema action plan: a randomized controlled
      trial.

PMID- 23553036
TI  - Efficacy of topical antifungals in the treatment of dermatophytosis: a mixed
      treatment comparison meta-analysis involving 14 treatments.
AB  - IMPORTANCE: Considering that most randomized controlled trials compare
      antifungals with placebo instead of other antifungals, conventional meta-analysis
      is insufficient to define superiority between the evaluated strategies. To our
      knowledge, this is the first mixed-treatment comparison meta-analysis on
      antifungal treatments in the literature and shows all the evidence available at
      the time of the study. OBJECTIVE: To evaluate and compare the efficacy of topical
      antifungals used in dermatophytosis treatment, using mixed-treatment comparisons.
      EVIDENCE ACQUISITION: We performed a comprehensive search (up to July 31, 2012)
      for all entries in MEDLINE, Cochrane Central Register of Controlled Trials,
      EMBASE, Literatura Latino Americana e do Caribe em Ciencias da Saude, and
      International Pharmaceutical Abstracts. Randomized controlled trials that
      compared topical antifungals with one another or with placebo in dermatophytosis
      treatment were selected for analysis. Methodologic quality of the trials was
      assessed using the Jadad scale. We excluded studies that scored less than 3
      points. The outcomes evaluated were mycologic cure at the end of treatment and
      sustained cure. A random-effects Bayesian mixed-treatment comparisons model was
      applied to combine placebo-controlled and direct topical antifungals comparison
      trials. RESULTS Pooled data of the 65 trials identified did not show any
      statistically significant differences among the antifungals concerning the
      outcome of mycologic cure at the end of treatment. Regarding the sustained cure
      outcome, butenafine hydrochloride and terbinafine hydrochloride were
      significantly more efficacious than were clotrimazole, oxiconazole nitrate, and
      sertaconazole nitrate. Terbinafine also demonstrated statistical superiority when
      compared with ciclopirox (ciclopiroxolamine), and naftifine hydrochloride showed
      better response compared with oxiconazole. No inconsistency was detected in the
      network of evidence for both outcomes, sustaining the validity of the mixed
      treatment comparisons results. CONCLUSIONS AND RELEVANCE: With the outcome
      mycologic cure at the end of treatment, there was no significant difference among
      the antifungals. Butenafine, naftifine, and terbinafine might be the best
      strategies for maintaining cured status. Because of the different costs of the
      antifungals, pharmacoeconomic analysis is required to identify the most efficient
      strategy for dermatophytosis management.

PMID- 23553037
TI  - Molecular characterization of anastrozole resistance in breast cancer: pivotal
      role of the Akt/mTOR pathway in the emergence of de novo or acquired resistance
      and importance of combining the allosteric Akt inhibitor MK-2206 with an
      aromatase inhibitor.
AB  - Acquisition of resistance to aromatase inhibitors (AIs) remains a major drawback
      in the treatment of estrogen receptor alpha (ERalpha)-positive breast cancers.
      The Res-Ana cells, a new model of acquired resistance to anastrozole, were
      established by long-term exposure of aromatase-overexpressing MCF-7 cells to this
      drug. These resistant cells developed ER-independent mechanisms of resistance and
      decreased sensitivity to the AI letrozole or to ERalpha antagonists. They also
      displayed a constitutive activation of the PI3K/Akt/mTOR pathway and a
      deregulated expression of several ErbB receptors. An observed increase in the
      phospho-Akt/Akt ratio between primary and matched recurrent breast tumors of
      patients who relapsed under anastrozole adjuvant therapy also argued for a
      pivotal role of the Akt pathway in acquired resistance to anastrozole. Ectopic
      overexpression of constitutively active Akt1 in control cells was sufficient to
      induce de novo resistance to anastrozole. Strikingly, combining anastrozole with
      the highly selective and allosteric Akt inhibitor MK-2206 or with the mTOR
      inhibitor rapamycin increased sensitivity to this AI in the control cells and was
      sufficient to overcome resistance and restore sensitivity to endocrine therapy in
      the resistant cells. Our findings lead to us proposing a model of anastrozole
      acquired resistance based on the selection of cancer-initiating-like cells
      possessing self-renewing properties, intrinsic resistance to anastrozole and
      sensitivity to MK-2206. Altogether, our work demonstrated that the Akt/mTOR
      pathway plays a key role in resistance to anastrozole and that combining
      anastrozole with Akt/mTOR pathway inhibitors represents a promising strategy in
      the clinical management of hormone-dependent breast cancer patients. 

PMID- 23553038
TI  - Treatment options in newly diagnosed glioblastoma.
AB  - OPINION STATEMENT: Regardless of MGMT status, standard of care for a patient with
      newly diagnosed glioblastoma (GBM), age <=70 years, and adequate functional
      status is radiation and concurrent temozolomide followed by adjuvant
      temozolomide. For elderly patients, recent studies have suggested that standard
      radiation, hypofractionated radiation, or single agent temozolomide are
      acceptable treatment options. Randomized phase III studies of bevacizumab in
      combination with radiation and temozolomide for newly diagnosed GBM have
      completed accrual. Preliminary results reveal a clear progression-free survival
      benefit. Overall survival appears unchanged although follow-up has not fully
      matured and cross-over to bevacizumab upon progression among control patients may
      limit definitive conclusions. Although bevacizumab in the upfront setting may be
      considered for a subset of patients, it should not be used routinely in newly
      diagnosed patients until final results are available. Clinical trials evaluating
      promising therapeutics given in combination with standard temozolomide
      chemoradiation are critically needed.

PMID- 23553039
TI  - Cardiovascular effects of diabetes drugs: making the dark ages brighter with
      Carolina.

PMID- 23553040
TI  - ACP Journal Club. Scores poorly predict major bleeding (c-statistics <= 0.61)
      during oral anticoagulant therapy.

PMID- 23553042
TI  - Yellow light gone wild: a tale of permanent laser hair removal with a 595-nm
      pulsed-dye laser.

PMID- 23553043
TI  - Effect of parboiling on the formation of resistant starch, digestibility and
      functional properties of rice flour from different varieties grown in Sri Lanka.
AB  - BACKGROUND: Hydrothermal treatment used in parboiling could induce formation of
      novel starch properties having potential food applications. In the current work,
      functional, digestible and retrogradation properties of flour from non-parboiled
      and steamed parboiled six rice varieties with high amylose content of around 30%
      but differing in length and width ratio were investigated and compared. RESULTS:
      The parboiling process reduced swelling volume and amylose leaching in all tested
      varieties. Among the varieties studied, the resistant starch content ranged from
      1.6% in AT 306 to 0.46% in BG 357. Parboiling reduced the resistant starch
      content in AT 306 by about 50%, but it did not significantly affect the resistant
      starch content of the other varieties. The amylose-lipid complex remained
      unchanged after parboiling. Amylopectin retrogradation was not observed in
      parboiled rice. Amylose retrogradation was not seen except for AT 306. Pasting
      behaviour of parboiled rice flours showed high pasting stability and low setback.
      Flours were more susceptible to enzymatic hydrolysis after parboiling. Partial
      gelatinisation during parboiling was sufficient to produce grains with excellent
      milling quality showing a head rice recovery that ranged from 98% to 100% among
      the varieties studied. CONCLUSION: Degree of gelatinisation is the most important
      factor that determines the high head rice recovery. High pasting stability and
      low setback of flour of parboiled rice indicate some potential food applications.

PMID- 23553044
TI  - Long-term neurocognitive outcomes of patients with end-stage renal disease during
      infancy.
AB  - BACKGROUND: End-stage renal disease (ESRD) during infancy has been associated
      with poor short-term neurocognitive outcomes. Limited information exists
      regarding long-term outcomes. METHODS: Neurocognitive outcomes for 12 patients
      diagnosed with ESRD during the first 16 months of life were assessed. Nine
      patients (mean age: 11 years) were compared to their healthy siblings (mean age:
      10 years) on measures of intellectual and executive functioning, memory, and
      academic achievement using paired-samples t tests. RESULTS: Patients' Full Scale
      IQ (FSIQ) scores (M = 78, SD = 16.1) were significantly lower than sibling
      controls (M = 94, SD = 18.9; p < 0.03). For patients, FSIQ negatively correlated
      with total months on dialysis (r = -0.6, p < 0.04), as did WISC-IV Processing
      Speed (r = -0.6, p < 0.05). Patients' scores on the Metacognition Index of the
      BRIEF (M = 61.4, SD = 16.3) were significantly higher (indicating greater risk
      for dysfunction) than siblings (M = 46.7, SD = 6.4; p < 0.04). Patients' scores
      (M = 84, SD = 19) on the WIAT-II-A Total Achievement were significantly lower
      than siblings (M = 103, SD = 20, p < 0.01). Younger age at transplant was
      associated with higher scores on measures of Processing Speed (r = -0.7, p <
      0.05), as well as higher scores on measures of executive functioning, memory, and
      academic achievement. CONCLUSIONS: In summary, patients diagnosed with ESRD as
      infants had intellectual and metacognitive functioning significantly lower than
      sibling controls. Fewer months on dialysis and younger age at transplant were
      associated with better outcomes.

PMID- 23553045
TI  - Extra-uterine renal growth in preterm infants: oligonephropathy and prematurity.
AB  - BACKGROUND: Nephron number in humans is determined during fetal life. The
      objective of this study was to investigate the effects of preterm birth on
      nephron number using renal volume as a surrogate for nephron number. METHODS:
      This observational study was conducted over 12 months in a tertiary perinatal
      center. Preterm babies less than 32 weeks of gestation were recruited and
      followed until discharge. Term infants were recruited for comparison. The babies
      underwent renal sonography and renal function measurements at 32 and 38 weeks
      corrected age. The primary outcome measurement was total kidney volume at 38
      weeks and the secondary outcome was estimated glomerular filtration rate (eGFR).
      RESULTS: Forty-four preterm infants and 24 term infants were recruited. At 38
      weeks corrected age, premature infants had lower total kidney volume than term
      infants (21.6 +/- 5.7 vs. 25.2 +/- 5.7 ml; p = 0.02) and a significantly lower
      eGFR (73.6 [IQR 68.1-77.6] vs. 79.3 [IQR 72.5-86.6] ml.min(-1).1.73 m(-2); p =
      0.03). There was a significant correlation between total kidney volume and eGFR
      in premature and term babies. CONCLUSIONS: Premature infants have smaller kidney
      volume and likely decreased nephron number and lower estimated
      glomerulofiltration rate relative to infants born at term.

PMID- 23553046
TI  - Radiotherapy for carcinoma of the vagina. Immunocytochemical and cytofluorometric
      analysis of prognostic factors.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to assess the potential
      prognostic factors in patients with primary invasive vaginal carcinoma (PIVC)
      treated with radical irradiation. PATIENTS AND METHODS: The analysis was
      performed on 77 patients with PIVC treated between 1985 and 2005 in the Maria
      Sklodowska-Curie Memorial Institute of Oncology, Cancer Center in Krakow. A total
      of 36 patients (46.8 %) survived 5 years with no evidence of disease (NED). The
      following groups of factors were assessed for potential prognostic value:
      population-based (age), clinical (Karnofsky Performance Score [KPS], hemoglobin
      level, primary location of the vaginal lesion, macroscopic type, length of the
      involved vaginal wall, FIGO stage), microscopic (microscopic type, grade, mitotic
      index, presence of atypical mitoses, lymphatic vessels invasion,
      lymphocytes/plasmocytes infiltration, focal necrosis, VAIN-3),
      immunohistochemical (protein p53 expression, MIB-1 index), cytofluorometric
      (ploidity, index DI, S-phase fraction, proliferation index SG2M) factors.
      RESULTS: Significantly better 5-year NED was observed in patients: < 60 years,
      KPS >= 80, FIGO stage I and II, grade G1-2, MIB-1 index  < 70, S-phase fraction <
      10, and proliferation index < 25. Independent factors for better prognosis in the
      multivariate Cox analysis were age < 60 years, FIGO stage I or II, and MIB-1
      index < 70. CONCLUSION: Independent prognostic factors in the radically
      irradiated PIVC patients were as follows: age, FIGO stage, MIB-1 index.

PMID- 23553047
TI  - Comparison of four target volume definitions for pancreatic cancer. Guidelines
      for treatment of the lymphatics and the primary tumor.
AB  - BACKGROUND AND PURPOSE: Target volume definitions for radiotherapy in pancreatic
      ductal adenocarcinoma (PDAC) vary substantially. Some groups aim to treat the
      primary tumor only, whereas others include elective lymph nodes (eLNs). eLNs
      close to the primary tumor are often included unintentionally within the
      treatment volume, depending on the respective treatment philosophies. We aimed to
      measure the percentages of anatomical coverage of eLNs by comparing four
      different contouring guidelines. PATIENTS AND METHODS: Planning target volumes
      (PTVs) were contoured using planning computed tomography (CT) scans of 11
      patients with PDAC based on the Oxford, RTOG (Radiation Therapy Oncology Group),
      Michigan, and SCALOP (Selective Chemoradiation in Advanced Localised Pancreatic
      Cancer trial) guidelines. Clinical target volumes (CTVs) included the
      peripancreatic, para-aortic, paracaval, celiac trunk, superior mesenteric, and
      portal vein lymph node areas. Volumetric comparisons of the coverage of all eLN
      regions were conducted to illustrate the differences between the four contouring
      strategies. RESULTS: The PTV sizes of the RTOG and Oxford guidelines were
      comparable. The SCALOP and Michigan PTV sizes were similar to each other and
      significantly smaller than the RTOG and Oxford PTVs. A large variability of eLN
      coverage was found for the various subregions according to the respective
      contouring strategies. CONCLUSION: This is the first study to directly compare
      the percentage of anatomical coverage of eLNs according to four PTVs in the same
      patient cohort. Potential practical consequences are discussed in detail.

PMID- 23553048
TI  - Analysis of thiopurine S-methyltransferase phenotype-genotype in a Tunisian
      population with Crohn's disease.
AB  - This study was conducted to investigate the thiopurine S-methyltransferase TPMT
      activity distribution and gene mutations in Tunisian population with positive
      diagnostic for Crohn's disease. TPMT activity was measured in Tunisian population
      (n = 88) by a high performance liquid chromatography assay. Polymerase chain
      reaction-based methods were used to determine the frequency of TPMT mutant
      alleles TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. TPMT activity was normally
      distributed, ranging from 4.58 to 35.27 nmol/(h ml) RBC with a mean of 18.67 +/-
      7.10 nmol/(h ml) RBC. Seven TPMT*3A heterozygotes and one TPMT*3C homozygote were
      found in 88 patients, with allele frequencies of 0.039 and 1.13, respectively.
      TPMT*3A and the TPMT*3C, which cause the largest decrease in enzyme activity,
      were both variant alleles detected in the Tunisian population.

PMID- 23553049
TI  - Disposition of ceftriaxone in hepatopathic goats following single-intramuscular
      dosing.
AB  - Hepatopathy sometimes may interfere with metabolism and/or elimination of drugs
      which undergo major hepatic clearance. Twelve healthy goats were equally divided
      into two groups (I and II) and hepatopathy was induced by carbontetrachloride in
      the second group (group II). A single dose of ceftriaxone at 50 mg/kg was
      administered to each group intramuscularly. Disposition of ceftriaxone in plasma
      of healthy goats showed a typical absorption-reabsorption phase. However, the
      reabsorption phase was totally absent in hepatopathic goats and the disposition
      of ceftriaxone showed only absorption and distribution/elimination phase. The
      drug persisted in plasma for 6 h in hepatopathic animals, whereas the drug can
      only be detected up to 2 h in healthy animals indicating longer persistence of
      ceftriaxone in the former group. Ceftizoxime, the active metabolite of
      ceftriaxone was available in urine of group I animals, whereas only ceftriaxone
      was detected in the urine of hepatopathic animals suggesting impairment of
      metabolism of the parent drug in hepatopathy. Therefore, the reabsorption and
      metabolism of ceftriaxone in goats should be taken into consideration for drug
      monitoring.

PMID- 23553050
TI  - To meet health care's triple aim, lean management must be applied across the
      value stream.

PMID- 23553051
TI  - Different postprandial acute response in healthy subjects to three strawberry
      jams varying in carbohydrate and antioxidant content: a randomized, crossover
      trial.
AB  - PURPOSE: Dietary food composition influences postprandial glucose homeostasis.
      Thus, the objective was to investigate the effects of an acute intake of three
      different types of strawberry jam, differing in carbohydrate and antioxidants
      content, on postprandial glucose metabolism, lipid profile, antioxidant status,
      and satiety. METHODS: Sixteen healthy adults participated in a randomized,
      crossover, double-blind study with three arms, receiving 60 g of three different
      strawberry jams. Blood samples were collected at fasting and at 30, 60, 90, and
      120 min after its intake. Blood analyses were performed with validated procedures
      and satiety was estimated with visual analogue scale (VAS). RESULTS: Blood
      glucose concentrations were maintained at normal values and without peaks within
      the 2 h after consumption of low-sugar jams. However, blood glucose and insulin
      were significantly higher at 30 and 60 min after high-sugar (HS) jam intake
      versus both low-sugar jams. Furthermore, HS jam produced more satisfaction at
      short time, but decreased as soon as blood glucose concentration began to
      decrease. Moreover, HS ingestion produced lower free fatty acid levels (p < 0.05)
      throughout the trial with respect both the low-sugar jams. However, no additional
      benefits on oxidative status (malondialdehyde, glutathione peroxidase, total
      antioxidant capacity, and uric acid), glucose, lipid, and satiety variables were
      observed due to the inclusion of an antioxidant to low-sugar jam. CONCLUSIONS:
      This study reinforces the idea that products without added sugars are appropriate
      for the management of glycemic alterations and provides further insight into the
      effect of natural antioxidants as a functional ingredient on oxidative status and
      related metabolic disturbances. Registered at www.clinicaltrials.gov as
      NCT01684332.

PMID- 23553052
TI  - Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a
      profound and convergent genetic reprogramming during their maturation.
AB  - DCs express receptors sensing microbial, danger or cytokine signals, which when
      triggered in combination drive DC maturation and functional polarization.
      Maturation was proposed to result from a discrete number of modifications in
      conventional DCs (cDCs), in contrast to a cell-fate conversion in plasmacytoid
      DCs (pDCs). cDC maturation is generally assessed by measuring cytokine production
      and membrane expression of MHC class II and co-stimulation molecules. pDC
      maturation complexity was demonstrated by functional genomics. Here, pDCs and
      cDCs were shown to undergo profound and convergent changes in their gene
      expression programs in vivo during viral infection. This observation was
      generalized to other stimulation conditions and DC subsets, by public microarray
      data analyses, PCR confirmation of selected gene expression profiles, and gene
      regulatory sequence bioinformatics analyses. Thus, maturation is a complex
      process similarly reshaping all DC subsets, including through the induction of a
      core set of NF-kappaB- or IFN-stimulated genes irrespective of stimuli. 

PMID- 23553053
TI  - Gastric emptying rate and chyme characteristics for cooked brown and white rice
      meals in vivo.
AB  - BACKGROUND: Rice structure is important to rice grain and starch breakdown during
      digestion. The objective of this study was to determine the gastric emptying and
      rice composition during gastric digestion of cooked brown and white medium-grain
      (Calrose variety) rice using the growing pig as a model for the adult human.
      RESULTS: Brown and white rice did not show significantly different gastric
      emptying rates of dry matter or starch, but brown rice had slower protein
      emptying (P < 0.05). Moisture content was greater and pH was lower in the distal
      stomach compared to the proximal stomach (P < 0.0001), and varied with time (P <
      0.0001). The mechanism of physical breakdown for brown and white rice varied.
      Brown rice exhibited an accumulation of bran layer fragments in the distal
      stomach, quantified by lower starch and higher protein content. CONCLUSION: The
      quantity of gastric secretions observed after a brown or white rice meal may be
      related to the meal buffering capacity, and are accumulated in the distal
      stomach. The delayed rate of protein emptying in brown rice compared to white
      rice was most likely due to the accumulation of bran layers in the stomach.

PMID- 23553055
TI  - BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in
      MSI-H colorectal cancer.
AB  - The differentiation between hereditary and sporadic microsatellite-unstable (MSI
      H) colorectal cancer is a crucial step in Lynch syndrome diagnostics. Within MSI
      H colorectal cancers, the BRAF V600E mutation is strongly associated with
      sporadic origin. Here, we asked whether BRAF V600E-specific immunohistochemistry
      (clone VE1) is helpful in separating sporadic from Lynch syndrome-associated MSI
      H colorectal cancers. To that end, we performed VE1 immunohistochemistry and BRAF
      sequencing in a series of 91 MSI-H colorectal cancer specimens from patients
      tested for Lynch syndrome. Concordance of VE1 immunohistochemistry and molecular
      BRAF mutation status was observed in 90 of 91 (98.9%) MSI-H samples. All 11
      tumors classified as BRAF V600E mutation-positive by Sanger sequencing were
      immunopositive, and 79 (98.8%) of 80 tumors classified as BRAF wild type showed
      negative staining. All VE1-positive tumors were MLH1- and PMS2-negative by
      immunohistochemistry. None of the tumors from mismatch repair (MMR) gene germline
      mutation carriers (n = 28) displayed positive VE1 staining, indicating that BRAF
      V600E mutation-specific immunostaining has a low risk of excluding Lynch syndrome
      patients from germline mutation analysis. In conclusion, implementation of VE1
      immunohistochemistry was able to detect BRAF-mutated MSI-H colorectal cancers
      with a sensitivity of 100% and a specificity of 98.8%. Among MLH1-negative
      colorectal cancers, the rate of VE1-positive lesions was 21%, offering the
      exclusion of these patients from MMR germline testing. Therefore, we suggest the
      integration of VE1 immunohistochemistry into the diagnostic panel of Lynch
      syndrome. 

PMID- 23553056
TI  - Inquiry is fatal to certainty-is the ultrasonography double contour sign specific
      for uric acid-induced arthritis?

PMID- 23553057
TI  - Enhancement of in vivo antioxidant ability in the brain of rats fed tannin.
AB  - The effect of the oral administration of mimosa tannin (MMT) on the rat intra
      hippocampal antioxidant ability was examined. Wistar rats at the age of 6 weeks
      were reared for 8 weeks with the rodent diet (RD) consisting of 0.1 g/kg of MMT
      (RD-MMT). The antioxidant ability of rat brain was evaluated from the decay of a
      brain-blood-barrier permeable stable nitroxide, 3-methoxycarbonyl-2,2,5,5
      tetramethylpyrrolidine-1-oxyl (PCAM) measured by the microdialysis-electron spin
      resonance system under a freely moving state. The decay rate of PCAM in the brain
      of rats fed RD-MMT was significantly larger than that of rats fed control rodent
      diet, which indicates the increase of the antioxidant ability in the brain of
      rats fed RD-MMT. In vitro study showed that MMT did not reduce PCAM directly but
      enhanced the reduction of PCAM by ascorbic acid. These results indicate that MMT
      is a potent antioxidant in vitro and in vivo.

PMID- 23553058
TI  - Performance of multinomial designs in comparison with response-based designs in
      non-randomized phase II trials of targeted cancer agents.
AB  - BACKGROUND: In phase II trials of cytotoxic agents, a multinomial phase II design
      incorporating early progression and response end points was shown to perform more
      efficiently than designs based only on response. We undertook a study to evaluate
      the performance of these designs in trials of targeted agents using the actual
      phase II data. PATIENTS AND METHODS: Using best response data from sequentially
      enrolled patients in 15 NCIC Clinical Trials Group and 7 European Organization
      for Research and Treatment of Cancer trials of targeted agents, we determined
      that trials would have been stopped at the end of stage I of accrual by applying
      rules generated by the multinomial and Fleming designs. Two variants of the
      multinomial design were studied: to stop accrual after stage I of enrolment,
      Variant A required either response or progression criteria to be met, whereas
      Variant B required that both response and progression criteria to be met.
      RESULTS: Using early progression, null/alternate hypotheses of 60% and 40%
      (60/40), the multinomial A variant recommended early stopping more often than the
      Fleming design. In most of the cases, this recommendation was correct given the
      final trial outcome. In contrast, the multinomial B variant never led to
      recommendations for early stopping and changing progression hypotheses did not
      improve the performance of this design. CONCLUSIONS: The multinomial A design
      using 60/40 hypotheses carried out better than the Fleming design in
      appropriately stopping trials of inactive targeted agents early. The multinomial
      B design was not useful for early stopping decisions. The multinomial A design
      may be favored over response-based designs in phase II trials of targeted agents.

PMID- 23553060
TI  - Comparing normal saline versus diluted heparin to lock non-valved totally
      implantable venous access devices in cancer patients: a randomised, non
      inferiority, open trial.
AB  - BACKGROUND: Heparin has been used for years as a locking solution in totally
      implantable venous access devices. Normal saline (NS) might be a safe alternative
      for heparin. However, evidence of non-inferiority of NS versus heparin is
      lacking. PATIENTS AND METHODS: We randomly allocated 802 cancer patients with a
      newly inserted port either to heparin lock (300 U/3 ml) or to NS lock groups in a
      1:1 assignment ratio. The primary outcome was the number of functional
      complications, which was defined as 'easy injection, impossible aspiration' at
      port access. Secondary outcomes included all functional problems and catheter
      related bacteraemia. We hypothesised that NS locks do not cause more functional
      problems and catheter-related bacteraemia than heparin locks. Non-inferiority is
      established if the upper limit of the confidence interval (CI) for the relative
      risk of NS versus heparin is <1.4. RESULTS: Three hundred and eighty-two patients
      from the NS group and 383 from the heparin lock group were included in the
      analysis. The incidence rate of our primary outcome (easy injection, impossible
      aspiration) was 3.70% (95% CI 2.91%-4.69%) and 3.92% (95% CI 3.09%-4.96%) of
      accesses in the NS and heparin groups, respectively. The relative risk was 0.94%
      (95% CI 0.67%-1.32%). Catheter-related bloodstream infection was 0.03 per 1000
      catheter days in the NS group and 0.10 per 1000 catheter days in the heparin
      group. CONCLUSION: NS is a safe and effective locking solution in implantable
      ports if combined with a strict protocol for device insertion and maintenance.

PMID- 23553061
TI  - Locoregional recurrence of early-stage surgically resected non-small-cell lung
      cancer: the importance of close follow-up and consistent definitions.

PMID- 23553059
TI  - Cruciferous vegetables consumption and the risk of female lung cancer: a
      prospective study and a meta-analysis.
AB  - BACKGROUND: Epidemiological studies evaluating the association between
      cruciferous vegetables (CVs) intake and female lung cancer risk have produced
      inconsistent results. PATIENTS AND METHODS: This study followed 74 914 Chinese
      women aged 40-70 years who participated in the Shanghai Women's Health Study. CV
      intake was assessed through a validated food-frequency questionnaire (FFQ) at
      baseline and reassessed during follow-up. Hazard ratios (HRs) and 95% confidence
      interval (CIs) were estimated by using Cox proportional hazards models.
      Furthermore, we carried out a meta-analysis of all observational studies until
      December 2011. RESULTS: After excluding the first 2 years of follow-up, 417 women
      developed lung cancer over a mean of 11.1 years of follow-up. An inverse
      association of borderline statistical significance was observed between CV
      consumption and female lung cancer risk, with HR for the highest compared with
      the lowest quartiles of 0.73 (95% CI 0.54-1.00, P trend = 0.1607). The
      association was strengthened in analyses restricting to never smokers, with the
      corresponding HR of 0.59 (95% CI 0.40-0.87, P trend = 0.0510). The finding of an
      inverse association between CV intake and lung cancer risk in women was supported
      by our meta-analysis of 10 included studies. CONCLUSIONS: Our study suggests that
      CV consumption may reduce the risk of lung cancer in women, particularly among
      never smokers.

PMID- 23553063
TI  - Spitz nevi: beliefs, behaviors, and experiences of pediatric dermatologists.
AB  - IMPORTANCE: Controversy exists regarding strategies for diagnosis and management
      of Spitz nevi, a type of melanocytic neoplasm that most often develops in
      children. OBJECTIVE: To determine the beliefs, behaviors, and experiences of
      pediatric dermatologists with regard to Spitz nevi. DESIGN: Anonymous web-based
      survey. SETTING: Private and academic dermatology practices. PARTICIPANTS:
      Respondents included 175 pediatric dermatologists from the United States and
      around the world, representing a 51.1% response rate (175 of 342). Analyses were
      limited to the 144 respondents whose practices included at least 50% children
      (younger than 18 years). MAIN OUTCOME MEASURES: Assessment of the following with
      regard to Spitz nevi: frequency of diagnosis, general beliefs, techniques used
      for evaluation (eg, dermoscopy and biopsy), management strategies, and observed
      outcomes. RESULTS: Collectively, respondents had seen approximately 20 000 Spitz
      nevi; 67.6% (96 of 142) had diagnosed at least 6 Spitz nevi yearly, whereas 90.1%
      (128 of 142) had diagnosed no more than 2 prepubertal melanomas in the past 5
      years. Ninety-six percent of respondents (95.8%; 136 of 142) categorized typical
      Spitz nevi as benign. Eighty percent of respondents (79.6%; 113 of 142) used
      dermatoscopy, and 96.5% (137 of 142) avoided partial biopsies of Spitz nevi. In
      children with a suspected Spitz nevus, clinical follow-up was chosen by 49.3% (69
      of 140) of respondents for a small, stable nonpigmented lesion and by 29.7% (41
      of 138) for a pigmented lesion with a typical starburst pattern seen via
      dermatoscopy. Predictors of clinical follow-up of the latter lesion included
      believing that Spitz nevi are not melanoma precursors (P = .04). Forty-seven
      percent (62 of 132) of respondents had observed involution of Spitz nevi. No
      deaths had resulted from the approximately 10 000 Spitz nevi or atypical spitzoid
      neoplasms seen by the 91 respondents with academic or hospital-based practices.
      CONCLUSIONS AND RELEVANCE: The results of our survey support conservative
      management of Spitz nevi in children, with clinical follow-up representing an
      option for typical lesions. This represents an important difference from
      strategies used for management of these lesions in adults.

PMID- 23553064
TI  - UV radiation protection by handheld umbrellas.

PMID- 23553062
TI  - Cancer prevalence estimates in Europe at the beginning of 2000.
AB  - BACKGROUND: Complete cancer prevalence data in Europe have never been updated
      after the first estimates provided by the EUROPREVAL project and referred to the
      year 1993. This paper provides prevalence estimates for 16 major cancers in
      Europe at the beginning of the year 2003. PATIENTS AND METHODS: We estimated
      complete prevalence by the completeness index method. We used information on
      cancer patients diagnosed in 1978-2002 with vital status information available up
      to 31 December 2003, from 76 European cancer registries. RESULTS: About 11.6
      millions of Europeans with a history of one of the major considered cancers were
      alive on 1 January 2003. For breast and prostate cancers, about 1 out of 73 women
      and 1 out of 160 men were living with a previous diagnosis of breast and prostate
      cancers, respectively. The demographic variations alone will increase the number
      of prevalent cases to nearly 13 millions in 2010. CONCLUSIONS: Several factors
      (early detection, population aging and better treatment) contribute to increase
      cancer prevalence and push for the need of a continuous monitoring of prevalence
      indicators to properly plan needs, resource allocation to cancer and for
      improving health care programs for cancer survivors. Cancer prevalence should be
      included within the EU official health statistics.

PMID- 23553065
TI  - Aretaeus of Cappadocia on leprosy's transmission.

PMID- 23553067
TI  - Regorafenib in Japanese patients with solid tumors: phase I study of safety,
      efficacy, and pharmacokinetics.
AB  - The safety, pharmacokinetics, and antitumor activity of the multikinase inhibitor
      regorafenib in Japanese patients was assessed in this multicenter, single-arm,
      phase I trial. Fifteen patients with treatment-refractory advanced solid tumors
      received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle
      until disease progression, unacceptable toxicity, or investigator or patient
      decision to stop. The median duration of treatment was 2.1 months (range, 0.9
      20.1 months). At data cutoff, one patient was still receiving regorafenib in
      cycle 21. Reasons for treatment discontinuation were disease progression (n = 12)
      and adverse events (liver enzyme elevation n = 1; anemia n = 1). Adverse events
      necessitated dose reduction in six patients, interruption of daily treatment in
      seven patients, and cycle delay in four patients. All patients experienced at
      least one drug-related adverse event, particularly gastrointestinal (87 %),
      dermatologic (73 %), or hematologic (67 %) events. There was no significant
      change in time to maximum concentration or terminal half-life of regorafenib and
      its active metabolites M2 and M5 between single dosing and 21-day continuous
      dosing. The area under the concentration-time curve was 2.1-fold higher for
      regorafenib, 5.2-fold higher for M2, and 37.3-fold higher for M5, and the maximum
      concentration was 2.0-fold, 4.8-fold, and 36.0-fold higher, respectively, after
      continuous dosing than after single dosing. One patient had a partial response
      (duration 10.5 months) and seven patients had stable disease. This study
      indicates that regorafenib 160 mg orally once daily (21 days on/7 days off
      treatment) can be given to Japanese patients who have solid tumors, without undue
      toxicity.

PMID- 23553066
TI  - A Phase I study of the combination of oxaliplatin/docetaxel and vandetanib for
      the treatment of advanced gastroesophageal cancer.
AB  - INTRODUCTION: This study aimed to assess the safety and tolerability of the
      multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two
      chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced
      gastroesophageal (GE) cancer. METHODS: This was a Phase I study (NCT00732745)
      with a standard 3+3 dose escalation design. The primary aim was to determine the
      optimal dose of the combination of vandetanib and OD chemotherapy. RESULTS:
      Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on
      day 1, docetaxel at 35 mg/m2 on days 1 and 8 and vandetanib 100 mg PO daily of 21
      day treatment cycles. As dose limiting toxicity (DLT) was reached in 2 out of 3
      patients in cohort 1 (one grade 3 and one grade 4 diarrhea with dehydration), 6
      patients were treated then at dose level -1 (O 80 mg/m2 on day 1, D 30 mg/m2 on
      days 1 and 8, V 100 mg PO daily days 1-21) in which no further DLTs were
      observed. This dose was established as maximum tolerated dose and is the
      recommended phase 2 dose. 8 out of 9 enrolled patients had adenocarcinoma. At
      dose level 1, 1 of the 3 patients had a documented partial response and 2
      patients had stable disease. At dose level -1, 1 of 6 patients achieved a
      complete response, 2 of 6 patients had stable disease, and 3 of 6 patients had
      progressive disease. CONCLUSIONS: Vandetanib added to oxaliplatin and docetaxel
      showed manageable toxicity and limited activity in advanced GE cancer.

PMID- 23553068
TI  - The diagnostic value of parathyroid hormone washout after fine-needle aspiration
      of suspicious cervical lesions in patients with hyperparathyroidism.
AB  - OBJECTIVES/HYPOTHESIS: We aimed to study the diagnostic value of parathyroid
      hormone (PTH) concentration in the needle washout of fine-needle aspiration (FNA)
      compared to cytology of suspicious lesions suggestive of culprit parathyroid
      glands in patients with recurrent or persistent primary hyperparathyroidism
      (PHPT). STUDY DESIGN: Retrospective review. METHODS: Patients with recurrent or
      persistent PHPT, who were referred to one surgeon and underwent FNA of the
      culprit parathyroid lesion preoperatively, were included in this study. All
      patients underwent comprehensive neck ultrasound, and suspicious lesions
      underwent ultrasound-guided FNA by the same surgeon. The aspiration cytology was
      read by a single dedicated cytopathologist blinded to the PTH washout results. A
      positive cutoff value for PTH washout concentration was defined as superior to
      serum PTH level obtained at the same time. The final diagnosis after reoperative
      surgery was confirmed by the same cytopathologist. RESULTS: Twenty-four
      consecutive patients were included. The mean serum PTH and calcium were 111.5 +/-
      106.25 pg/mL (normal: 15-65 pg/mL) and 10.8 +/- 0.5 mg/dL (normal: 8.6-10.2
      pg/mL), respectively. Twenty-two patients (91.6%) had elevated PTH washout
      concentrations with a positive predictive value (PPV) of 100%. Cytopathology was
      successful in confirming parathyroid tissue only in seven patients (29%). An
      adenoma was identified in 19 patients (79.1%); however, five patients (20.8%)
      were found to have multiglandular disease. CONCLUSIONS: An elevated PTH washout
      concentration can help identify culprit parathyroid gland lesions with a high PPV
      in patients requiring reoperative parathyroid surgery. This diagnostic technique
      allows for targeted surgical approach in reoperative settings, especially in
      patients with negative preoperative sestamibi scans. LEVEL OF EVIDENCE: 4.

PMID- 23553071
TI  - CORR Insights(r): Variations in the use of diagnostic criteria for developmental
      dysplasia of the hip.

PMID- 23553069
TI  - Is the transplant quality at the time of surgery adequate for matrix-guided
      autologous cartilage transplantation? A pilot study.
AB  - BACKGROUND: Matrix-guided autologous chondrocyte transplantation (MACT) has been
      proposed as an option for treating large full-thickness cartilage defects.
      However, little is known about the chondrogenic potential of transplants for MACT
      at the time of implantation, although cell quality and chondrogenic
      differentiation of the implants are crucial for restoration of function after
      MACT. QUESTIONS/PURPOSES: We therefore asked: (1) Do MACT implants allow
      deposition of extracellular cartilage matrix in an in vitro culture model? (2)
      Are these implants associated with improved knee function 1 year after MACT in
      large cartilage defects? METHODS: We retrospectively reviewed all 125 patients
      with large localized cartilage defects (mean defect size 5 cm(2)) of the knee who
      were treated with MACT from 2005 to 2010. The mean age was 31 years (range, 16-53
      years). Portions of the cell-matrix constructs (n = 50) that were not implanted
      in the cartilage defects were further cultured and tested for their potential to
      form articular cartilage. Knee function of all patients was analyzed
      preoperatively, 3 months, and 1 year postoperatively with the International Knee
      Documentation Committee (IKDC) score. RESULTS: In vitro assessment of the cell
      matrix implants showed chondrogenic differentiation with positive staining for
      glycosaminoglycans and collagen II in all cultures. Enzyme-linked immunosorbent
      assay showed an increase of collagen II production. We observed an improvement in
      median IKDC score from 41 to 67 points at last followup. CONCLUSIONS: Cartilage
      extracellular matrix deposition shows adequate implant quality for MACT at the
      time of implantation and justifies the use for treatment of large cartilage
      defects.

PMID- 23553072
TI  - Surgical technique: Unicondylar osteoallograft prosthesis composite in tumor limb
      salvage surgery.

PMID- 23553073
TI  - Reply to letter to the editor: Surgical technique: Unicondylar osteoallograft
      prosthesis composite in tumor limb salvage surgery.

PMID- 23553075
TI  - Eliciting preferences to the EQ-5D-5L health states: discrete choice experiment
      or multiprofile case of best-worst scaling?
AB  - Choice-based methods have been used widely in assessing healthcare programs. This
      study compared the binary discrete choice experiment (DCE) and the multiprofile
      case of best-worst scaling (BWS) in eliciting preferences for the EQ-5D-5L. Forty
      eight EQ-5D-5L health states were selected using a Bayesian efficient design and
      grouped into 24 pairs for the DCE tasks and 8 sets for the BWS tasks (each set
      has three health states). A total of 100 participants completed 12 pairs and 8
      sets in a random order. A probit regression model and ranked order logistic
      regression model were used to estimate the latent utilities from the DCE and BWS,
      respectively. Both tasks were well understood by the majority of participants.
      The DCE tasks were relatively easier and took a shorter time to complete. The
      intraclass correlation coefficient (ICC) of the DCE was higher than that of the
      BWS. The variances associated with the latent utilities estimated from the DCE
      were larger than those from the BWS. The DCE is more feasible and reliable than
      the BWS in valuing the EQ-5D-5L. Future studies could focus on comparing the
      consistency and accuracy of these techniques in predicting the health utilities
      of the EQ-5D-5L.

PMID- 23553074
TI  - First insights into the metagenome of Egyptian mummies using next-generation
      sequencing.
AB  - We applied, for the first time, next-generation sequencing (NGS) technology on
      Egyptian mummies. Seven NGS datasets obtained from five randomly selected Third
      Intermediate to Graeco-Roman Egyptian mummies (806 BC-124AD) and two unearthed
      pre-contact Bolivian lowland skeletons were generated and characterised. The
      datasets were contrasted to three recently published NGS datasets obtained from
      cold-climate regions, i.e. the Saqqaq, the Denisova hominid and the Alpine
      Iceman. Analysis was done using one million reads of each newly generated or
      published dataset. Blastn and megablast results were analysed using MEGAN
      software. Distinct NGS results were replicated by specific and sensitive
      polymerase chain reaction (PCR) protocols in ancient DNA dedicated laboratories.
      Here, we provide unambiguous identification of authentic DNA in Egyptian mummies.
      The NGS datasets showed variable contents of endogenous DNA harboured in tissues.
      Three of five mummies displayed a human DNA proportion comparable to the human
      read count of the Saqqaq permafrost-preserved specimen. Furthermore, a
      metagenomic signature unique to mummies was displayed. By applying a "bacterial
      fingerprint", discrimination among mummies and other remains from warm areas
      outside Egypt was possible. Due to the absence of an adequate environment
      monitoring, a bacterial bloom was identified when analysing different biopsies
      from the same mummies taken after a lapse of time of 1.5 years. Plant kingdom
      representation in all mummy datasets was unique and could be partially associated
      with their use in embalming materials. Finally, NGS data showed the presence of
      Plasmodium falciparum and Toxoplasma gondii DNA sequences, indicating malaria and
      toxoplasmosis in these mummies. We demonstrate that endogenous ancient DNA can be
      extracted from mummies and serve as a proper template for the NGS technique,
      thus, opening new pathways of investigation for future genome sequencing of
      ancient Egyptian individuals. 

PMID- 23553076
TI  - Image of the month. Locally advanced breast cancer.

PMID- 23553077
TI  - Vitamin D in systemic lupus erythematosus: modest association with disease
      activity and the urine protein-to-creatinine ratio.
AB  - OBJECTIVE: To investigate whether an increase in vitamin D levels in patients
      with systemic lupus erythematosus (SLE) was associated with improvement in
      disease activity. METHODS: A total of 1,006 SLE patients were monitored over 128
      weeks. SLE patients with low levels of 25-hydroxyvitamin D (25[OH]D; <40 ng/ml)
      were given supplements of 50,000 units of vitamin D2 weekly plus 200 units of
      calcium/vitamin D3 twice daily. Longitudinal regression models were used to
      estimate the association between levels of 25(OH)D and various measures of
      disease activity. RESULTS: The SLE patients had the following characteristics:
      91% were female, their mean age was 49.6 years, and their ethnicity was 54%
      Caucasian, 37% African American, and 8% other. For those with levels of 25(OH)D
      <40 ng/ml, a 20-unit increase in the 25(OH)D level was associated with a mean
      decrease of 0.22 (95% confidence interval [95% CI] -0.41, -0.02) (P = 0.032) in
      the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)
      version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This
      corresponded to a 21% decrease in the odds of having a SELENA-SLEDAI >=5 (95% CI
      1, 37). The mean urine protein-to-creatinine ratio decreased by 2% (95% CI -0.03,
      -0.01) (P = 0.0001), corresponding to a 15% decrease in the odds of having a
      ratio >0.5 (95% CI 2, 27). CONCLUSION: We found that a 20-ng/ml increase in the
      25(OH)D level was associated with a 21% decrease in the odds of having a high
      disease activity score and a 15% decrease in the odds of having clinically
      important proteinuria. Although these associations were statistically
      significant, the clinical importance is relatively modest. There was no evidence
      of additional benefit of 25(OH)D beyond a level of 40 ng/ml.

PMID- 23553078
TI  - Structure analysis and antimutagenic activity of a novel salt-soluble
      polysaccharide from Auricularia polytricha.
AB  - BACKGROUND: Auricularia polytricha is known to be a highly nutritious foodstuff.
      We report here the purification, structure characterization and antimutagenic
      activity in vivo of a 0.9% NaCl solution-soluble polysaccharide (SSP) from the
      mycelia of A. polytricha. RESULTS: Analysis by high-performance liquid
      chromatography coupled to a TSK-G5000PWXL column and gel filtration
      chromatography on Sephacryl S-400 HR indicated that SSP is homogeneous with an
      average molecular weight of about 9.30 * 10(5) Da. The structure of SSP was
      revealed by chemical methods, Fourier transform infrared spectroscopy and nuclear
      magnetic resonance spectroscopy. Results indicated that SSP is a glucan
      consisting of a1,3-beta-glucan, 1,6-alpha-glucan, 1,4-alpha-glucan and 1,3-alpha
      glucan backbone with a single 1,6-alpha-d-glucopyranosyl side-branching unit on
      every nine residues, on average, along the main chain. Atomic force microscopy
      indicates the presence of macromolecular species in morphology and shows a clear
      association of prolate particle. Meanwhile, SSP was found to significantly
      preventing micronuclei in polychromatic erythrocytes and reticulocytes of mice (P
      < 0.01). CONCLUSION: These results indicate that polysaccharide SSP from A.
      polytricha exhibits antimutagenic activity against the in vivo DNA-damaging
      effect of the indirectly acting alkylating agent cyclophosphamide.

PMID- 23553079
TI  - Computers and the diagnosis of pneumonia.

PMID- 23553080
TI  - Distinct patterns of medial temporal impairment in degenerative dementia: a brain
      SPECT perfusion study in Alzheimer's disease and frontotemporal dementia.
AB  - PURPOSE: Medial temporal impairment can be detected clinically and by
      morphological imaging during Alzheimer's disease (AD), but the existence of a
      functional impairment in this area seems to be less well established. Yet such
      functional impairment is classically found in other degenerative cortical
      dementias, such as the frontal variant of frontotemporal dementia (fv-FTD). The
      aim of this study was to characterize and compare brain SPECT perfusion of the
      medial temporal lobe in AD and fv-FTD. METHODS: Voxel-based comparisons were
      performed using SPM8 between cerebral SPECT images from 85 AD patients, 25 fv-FTD
      patients and 12 healthy controls at the whole-brain level and the medial temporal
      lobe level using a region of interest approach (p < 0.001, corrected for the
      cluster). RESULTS: In the free and cued selective reminding test, used to
      evaluate medial temporal memory function, AD patients had significantly lower
      scores than the fv-FTD patients (p < 0.005). AD and fv-FTD patients showed
      hypoperfused medial temporal structures in comparison to normal controls.
      However, fv-FTD patients had more pronounced hypoperfusion in this area, with a
      different topography, more anterior and more parahippocampal. CONCLUSION: These
      results show that medial temporal hypoperfusion can be detected in degenerative
      dementias by SPECT. Paradoxically, the hypoperfusion is more severe in fv-FTD
      than in AD patients, even though the mnesic profile of AD is more altered,
      suggesting the existence of inefficient compensatory mechanisms.

PMID- 23553081
TI  - Myocardial perfusion reserve in spared myocardium: correlation with infarct size
      and left ventricular ejection fraction.
AB  - PURPOSE: Left ventricular ejection fraction (LVEF) after myocardial infarction is
      considered to be determined by the size of the infarction and residual function
      of the spared myocardium. Myocardial perfusion reserve (MPR) has been shown to be
      a strong prognostic factor in patients with ischaemic heart failure, even
      stronger than LVEF. In the present study, the interrelationship between MPR, LVEF
      and infarct size was investigated. METHODS: In total, 102 patients with a prior
      history of myocardial infarction were included. All underwent rest and stress
      (13)N-ammonia and gated (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission
      tomography (PET) for evaluation of myocardial ischaemia and viability. FDG polar
      maps were used to determine the size of the infarction. The LVEF was obtained by
      gated (18)F-FDG PET or another available method within 3 months of the PET scan.
      MPR was obtained per segment in the spared myocardium. RESULTS: The mean age of
      the subjects was 68 +/- 12 years. Global MPR was 1.63 +/- 0.51. The mean LVEF was
      36 +/- 10 % and mean infarct size 23.72 +/- 14.8 %. A linear regression model was
      applied for the analysis considering the LVEF as a dependent variable. All risk
      factors, mean stress flow, infarct size and MPR were entered as variables. The
      infarct size (p < 0.001) and MPR (p = 0.04) reached statistical significance. In
      a multivariate model MPR had a stronger correlation with LVEF than infarct size.
      CONCLUSION: In patients with a prior history of myocardial infarction, LVEF is
      not just related to infarct size but also to MPR in the spared myocardium.

PMID- 23553084
TI  - Conflicts of interest.

PMID- 23553082
TI  - Targeted ablation of the histidine-rich Ca(2+)-binding protein (HRC) gene is
      associated with abnormal SR Ca(2+)-cycling and severe pathology under pressure
      overload stress.
AB  - The histidine-rich Ca(2+)-binding protein (HRC) is located in the lumen of the
      sarcoplasmic reticulum (SR) and exhibits high-capacity Ca(2+)-binding properties.
      Overexpression of HRC in the heart resulted in impaired SR Ca(2+) uptake and
      depressed relaxation through its interaction with SERCA2a. However, the
      functional significance of HRC in overall regulation of calcium cycling and
      contractility is not currently well defined. To further elucidate the role of HRC
      in vivo under physiological and pathophysiological conditions, we generated and
      characterized HRC-knockout (KO) mice. The KO mice were morphologically and
      histologically normal compared to wild-type (WT) mice. At the cellular level,
      ablation of HRC resulted in significantly enhanced contractility, Ca(2+)
      transients, and maximal SR Ca(2+) uptake rates in the heart. However, after
      contractions were developed in 50 % of HRC-KO cardiomyocytes, compared to 11 % in
      WT mice under stress conditions of high-frequency stimulation (5 Hz) and
      isoproterenol application. A parallel examination of the electrical activity
      revealed significant increases in the occurrence of Ca(2+) spontaneous SR Ca(2+)
      release and delayed afterdepolarizations with ISO in HRC-KO, compared to WT
      cells. The frequency of Ca(2+) sparks was also significantly higher in HRC-KO
      cells with ISO, consistent with the elevated SR Ca(2+) load in the KO cells.
      Furthermore, HRC-KO cardiomyocytes showed significantly deteriorated cell
      contractility and Ca(2+)-cycling caused possibly by depressed SERCA2a expression
      after transverse-aortic constriction (TAC). Also HRC-null mice exhibited severe
      cardiac hypertrophy, fibrosis, pulmonary edema and decreased survival after TAC.
      Our results indicate that ablation of HRC is associated with poorly regulated SR
      Ca(2+)-cycling, and severe pathology under pressure-overload stress, suggesting
      an essential role of HRC in maintaining the integrity of cardiac function.

PMID- 23553085
TI  - Virtuous cycles: patient care, education, and scholarship in the patient-centered
      medical home.
AB  - BACKGROUND: Family medicine needs to enhance its scholarly contributions. The
      discipline is beginning to do so by developing virtuous cycles in which
      scholarship, education, and clinical care in the patient centered medical home
      are mutually reinforcing.

PMID- 23553086
TI  - The R.O.A.D. confirmed: ratings of specialties' lifestyles by fourth-year US
      medical students with a military service obligation.
AB  - BACKGROUND AND OBJECTIVES: Lifestyle factors influence medical specialty choice,
      but which specialties are perceived to have the best lifestyles is poorly
      described in scientific literature. The objective of the study was to determine
      the rating of specialties by lifestyle. METHODS: All fourth-year US medical
      students with a Department of Defense service obligation who participated in the
      2008/2009 military Match were invited to participate in a survey following the
      Match. The survey listed 18 specialties and asked students to rate the lifestyle
      of each one on a 9-point scale, and the mean score was used as the rating.
      Students also listed their specialty choice in the Match. RESULTS: The response
      rate was 52%, as 418 of the 797 eligible students responded and provided a rating
      for at least nine of the 18 specialties. The four specialties rated highest for
      lifestyle (1--9, with 9 being highest) were dermatology (8.4), radiology (8.1),
      ophthalmology (8.0), and anesthesia (7.5). The four specialties rated lowest were
      orthopedics (4.0), neurosurgery (3.1), general surgery (2.6), and obstetrics
      gynecology (2.5). Family medicine (5.7) was the top-rated primary care specialty,
      followed by pediatrics (5.3) and internal medicine (4.7). Students rated the
      lifestyle of their own specialty only slightly higher (range 0.02 to 1.8) than
      all other students. CONCLUSIONS: The R.O.A.D. specialties (radiology,
      ophthalmology, anesthesia, and dermatology) are the top specialties with respect
      to lifestyle as viewed by current students. Students perceive their own
      specialty's lifestyle realistically. Research determining why a specialty
      perceived as having a lower-rated lifestyle is acceptable to some students and
      not others is needed.

PMID- 23553087
TI  - A survey of exercise stress test training in US family medicine residency
      programs.
AB  - BACKGROUND AND OBJECTIVES: Only 12 % of family physicians perform exercise stress
      testing (EST) in the office even though there are many indications for its use.
      The purpose of this study was to obtain updated information about attitudes
      toward EST training from family medicine residency program directors in the
      United States. METHODS: A survey regarding EST training was designed and sent to
      all US family medicine residency program directors by e-mail and online survey
      method with telephone follow-up for non- respondents. RESULTS: A total of 179
      responses were received from 440 US family medicine programs, for a 41% response
      rate. A majority (77%) of program directors felt office-based EST was a valuable
      test for risk stratification, and 64% felt that family physicians should offer
      this test in the office. Despite these attitudes, only 33% of family medicine
      residency programs offer EST in their offices now, and only 36% of programs
      reported offering EST training to their residents. This reflects a 16% reduction
      compared to the last survey done in 1993. The most important barriers to EST
      training reported were lack of equipment and lack of expert faculty. DISCUSSION:
      Most family medicine training programs want to train their residents in
      performing EST, but only 36% are doing so. Specifically addressing the barriers
      to this training will be key to more widespread use of this important test in
      family medicine settings.

PMID- 23553088
TI  - Mid-to-late-life women and sexual health: communication with health care
      providers.
AB  - BACKGROUND AND OBJECTIVES: Sexual health communication can be difficult for aging
      women as well as their health care providers. The current exploratory study was
      undertaken to learn more about how mid-to-late-life women approached
      communication about sexual health with their health care providers and what
      factors impacted their perceptions of their abilities to do so. METHODS: In this
      descriptive qualitative study, 27 community-dwelling women, ages 50--80, were
      interviewed about their perceptions of their abilities to communicate with their
      health care providers about their sexual health. Interview data was coded for
      major themes. RESULTS: All of the women in the study had self efficacy to
      communicate about their sexual health, especially if there was a physical problem
      present. For a majority of women, provider-related behaviors impacted their
      communication self efficacy. Provider-related behaviors that both encouraged and
      hindered communication were identified. Relationship quality and provider
      initiated communication were among the behaviors that encourage communication
      about sexual health. Women in this sample valued active listening by the provider
      as well as a nonjudgmental stance. Perceptions of provider discomfort, lack of
      time or interest, as well as confidentiality concerns were identified as barriers
      to communication about sexual health. CONCLUSIONS: Sexual health is important to
      the quality of life of aging and older women. Providers can incorporate some of
      the behaviors identified as enhancing of communication self efficacy so that this
      important health topic is covered in the clinical encounter.

PMID- 23553089
TI  - Academic family physicians' perception of genetic testing and integration into
      practice: a CERA study.
AB  - BACKGROUND AND OBJECTIVES: Genetic testing for a variety of diseases is becoming
      more available to primary care physicians, but it is unclear how useful
      physicians perceive these tests to be. We examined academic family physicians'
      perception of and experiences with clinical genetic testing and direct-to
      consumer genetic testing. METHODS: This study is an analysis of a survey
      conducted as part of the Council of Academic Family Medicine Educational Research
      Alliance (CERA). Academic family physicians in the United States and Canada were
      queried about their perception of genetic testing's utility, how frequently
      patients ask about genetic testing, and the importance of genetic testing in
      future practice and education of students and residents. RESULTS: The overall
      survey had a response rate of 45.1% (1,404/3,112). A majority (54.4%) of
      respondents felt that they were not knowledgeable about available genetic tests.
      Respondents perceived greater utility of genetic tests for breast cancer (94.9%)
      and hemochromatosis (74.9%) than for Alzheimer's disease (30.3%), heart disease
      (25.4%), or diabetes (25.2%). Individuals with greater self-perceived knowledge
      of genetic tests were more likely to feel that genetic testing would have a
      significant impact on their future practice (23.1%) than those with less
      knowledge (13.4%). Respondents had little exposure to direct-to-consumer genetic
      tests, but a majority felt that they were more likely to cause harm than benefit.
      CONCLUSIONS: Academic family physicians acknowledge their lack of knowledge about
      genetic tests. Educational initiatives may be useful in helping them incorporate
      genetic testing into practice and in teaching these skills to medical students
      and residents.

PMID- 23553090
TI  - The association between global health training and underserved care: early
      findings from two longstanding tracks.
AB  - BACKGROUND AND OBJECTIVES: Global health tracks (GHTs) improve knowledge and
      skills, but their impact on career plans is unclear. The objective of this
      analysis was to determine whether GHT participants are more likely to practice in
      underserved areas than nonparticipants. METHODS: In this retrospective cohort
      study, using the 2009 American Medical Association Masterfile, we assessed the
      practice location of the 480 graduates from 1980--2008 of two family medicine
      residencies-Residency 1 and Residency 2. The outcomes of interest were the
      percentage of graduates in health professional shortage areas (HPSAs), medically
      underserved areas (MUAs), rural areas, areas of dense poverty, or any area of
      underservice. RESULTS: Thirty-seven percent of Residency 1 participants and 20%
      of nonparticipants practiced in HPSAs; 69% of Residency 2 participants and 55.5%
      of nonparticipants practiced in areas of dense poverty. All other combined and
      within-residency differences were not statistically significant. CONCLUSIONS:
      These findings neither confirm nor refute the results of prior surveys suggesting
      that global health training is associated with increased interest in underserved
      care. Studies involving more GHTs and complimentary methods are needed to more
      precisely elucidate the impact of this training.

PMID- 23553091
TI  - Challenges to depression care documentation in an EHR.
AB  - BACKGROUND AND OBJECTIVES: Patients with depression most frequently present in
      primary care. Electronic health records (EHR) have the potential to improve
      depression care through improved clinical documentation and information exchange.
      This report provides an example of how an EHR can fail to capture important
      information regarding depression care. METHODS: A 6-month baseline period in 2009
      was defined to identify ambulatory patients age 18 or older in the EHR with an
      ICD-9 coded new depression diagnosis. Data was abstracted electronically, and
      charts were reviewed by hand for patient demographics and to assess the clinical
      documentation of depression screening, diagnosis, and treatment practices among
      four community-based family medicine clinics. RESULTS: Electronic abstraction of
      baseline data identified 200 adult patients with a documented new diagnosis of
      depression. Review of charts by hand was required to obtain clinical
      documentation of screening (9% of patients), use of diagnostic tools (73%),
      discussion of treatment options (83%), medication treatment (71%), and follow-up
      characteristics (75%). CONCLUSIONS: Despite having a robust EHR, we encountered
      significant challenges finding documentation of depression care, which also made
      it difficult to track and evaluate the implementation of evidence-based
      treatment. Clinical documentation in the EHR needs to be simplified and
      standardized if data extraction and exporting processes of clinician performance
      data are to become efficient and routine practice.

PMID- 23553092
TI  - Learning together to work together: interprofessional education for students in a
      primary care setting in chile.
AB  - BACKGROUND AND OBJECTIVES: Interprofessional teamwork and collaboration are
      considered key elements for improving patient outcomes; however, few reports of
      interprofessional education experiences in primary care directed to students are
      found in the literature. We describe an educational program in primary care for
      medical, nursing, and psychology students and report the findings of their
      perceptions of learning. METHODS: To develop team-working skills and learn family
      oriented collaborative care in primary care, the authors designed an
      interprofessional educational course in Santiago, Chile. Medical, nursing, and
      psychology students, in their last year of training, formed four groups and
      conducted weekly home visits or behavioral health counseling sessions. A family
      physician, nurse practitioner, social worker, and psychologist supervised each
      clinical activity in their area of expertise. After the clinical encounters,
      students and preceptors discussed comprehensive health plans and reflected on the
      interprofessional experience of care. At the end of the course the students
      evaluated the course and the methodology using quantitative and qualitative
      methods. RESULTS: A total of 72 students participated in the course (58 medical,
      eight nursing, six psychology students) from October 2009 to December 2010. The
      students ranked high global satisfaction, high achievement of course objectives,
      and high approval of the methodology used with quantitative and qualitative
      measurements. CONCLUSIONS: This interprofessional course for medical, nursing,
      and psychology students generated positive experiences for the participants. More
      research is needed to support interprofessional education programs in primary
      care.

PMID- 23553093
TI  - Healing anger.

PMID- 23553096
TI  - Income ratio and medical student specialty choice: the primary importance of the
      ratio of mean primary care physician income to mean consulting specialist income.

PMID- 23553097
TI  - Pulse: celebrating narrative in family medicine.

PMID- 23553098
TI  - The Statue of Liberty's complexion.

PMID- 23553099
TI  - The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal
      and neoplastic cells.
AB  - BORIS and CTCF are paralogous, multivalent 11-zinc finger transcription factors
      that play important roles in organizing higher-order chromatin architecture.
      BORIS is a cancer-testis antigen with a poorly defined function in cancer,
      although it has been hypothesized to exhibit oncogenic properties. CTCF, however,
      has been postulated as a candidate tumor suppressor. We collated the genetic
      lesions in BORIS and CTCF from multiple cancers identified using high-throughput
      genomics. In BORIS, nonsense and missense mutations are evenly distributed. In
      CTCF, recurrent mutations are mostly clustered in the conserved zinc finger
      domain and at residues critical for contacting DNA and zinc ion co-ordination.
      Three missense mutations are common to both proteins. We used an inducible
      lentivector to express wildtype BORIS or CTCF in primary cells and cancer cell
      lines in order to define their functional differences. Both BORIS and CTCF caused
      a significant decrease in cell proliferation and clonogenic capacity, without
      alteration of specific cell cycle phases. Both BORIS and CTCF conferred
      protective effects in primary cells and some cancer cells during UV damage
      induced apoptosis. Using a bioluminescent MCF-7 orthotopic breast cancer model in
      vivo, we demonstrated that CTCF and BORIS suppressed breast cancer growth. These
      findings provide further evidence that CTCF behaves as a tumor suppressor, and
      show BORIS has a similar growth inhibitory effect in vitro and in vivo. Hence,
      acquired zinc finger mutations may disrupt these functions, thereby contributing
      to tumor growth and development. 

PMID- 23553100
TI  - Association between testosterone levels and risk of future rheumatoid arthritis
      in men: a population-based case-control study.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is less common among men than women, and
      sex hormones have been suggested to play a part in the pathogenesis. Lower levels
      of testosterone have been demonstrated in men with RA, but it is not known if
      these changes precede the disease. METHODS: In a nested case-control study, using
      information and blood samples from a population-based health survey, we
      identified incident cases of RA by linking the cohort to local and national RA
      registers. Two controls for each validated case, matched for age, sex and year of
      screening, were selected from the health survey. Using stored blood samples,
      collected between 08:00 and 10:00 am after an overnight fast, we analysed levels
      of testosterone and other reproductive hormones. RESULTS: Serum was available
      from 104 cases (median time from screening to RA diagnosis 12.7 years (range 1
      28); 73% rheumatoid factor (RF) positive at diagnosis or later) and 174 matched
      controls. In conditional logistic regression models, adjusted for smoking and
      body mass index, lower levels of testosterone were associated with subsequent
      development of RF-negative RA (OR 0.31 per SD, 95% CI 0.12 to 0.85), with a
      weaker association with RF-positive RA (OR 0.87 per SD; 95% CI 0.53 to 1.43).
      Levels of follicle-stimulating hormone were significantly increased in pre-RF
      negative RA (p=0.02), but decreased in pre-RF-positive RA (p=0.02). CONCLUSIONS:
      Lower levels of testosterone were predictive of RF-negative RA, suggesting that
      hormonal changes precede the onset of RA and affect the disease phenotype.

PMID- 23553101
TI  - Biodegradation of alpha-, beta-, and gamma-hexachlorocyclohexane by Arthrobacter
      fluorescens and Arthrobacter giacomelloi.
AB  - The organochlorine pesticide gamma-hexachlorocyclohexane (gamma-HCH, lindane) and
      its non-insecticidal isomers alpha-, beta-, and delta- continue to pose serious
      environmental and health concerns, although their use has been restricted or
      completely banned for decades. The present study reports the first results on the
      ability of two Arthrobacter strains, not directly isolated from a HCH-polluted
      site, to grow in a mineral salt medium containing alpha-, beta-, or gamma-HCH
      (100 mgl(-1)) as sole source of carbon. Growth of cultures and HCHs degradation
      by Arthrobacter fluorescens and Arthrobacter giacomelloi were investigated after
      1, 2, 3, 4, and 7 days of incubation by enumerating colony forming units and GC
      with ECD detection, respectively. Both bacteria are able to metabolize the HCHs:
      A. giacomelloi is the most effective one, as after 72 h of incubation it produces
      88 % degradation of alpha-, 60 % of beta-, and 56 % of gamma-HCH. The formation
      of possible persistent compounds was studied by GC/MS and by HPLC analysis.
      Pentachlorocyclohexenes and tetrachlorocyclohexenes have been detected as
      metabolites, which are almost completely eliminated after 72 h of incubation,
      while no phenolic compounds were found.

PMID- 23553102
TI  - Purification and characterization of a new serine protease with fibrinolytic
      activity from the marine invertebrate, Urechis unicinctus.
AB  - A non-hemorrhagic, chymotrypsin-like serine protease, UFEII, was purified from
      the marine echiuroid worm, Urechis unicinctus, after a combination of
      chromatography steps. UFEII was monomeric, with an apparent molecular weight of
      26.7 kDa via SDS-PAGE. The isoelectric point of UFEII was 4.03, and the maximum
      activity of the enzyme was observed at 50  degrees C and pH8.0. According to
      fibrin plate assays, UFEII could not only directly degrade fibrin and fibrinogen
      but also activate plasminogen. Further, UFEII preferentially hydrolyzed the
      fibrinogen gamma-chain, followed by the Bbeta-chains and Aalpha-chains. Moreover,
      ufeII, full length of the gene encoding UFEII, was obtained by RT-PCR,
      degenerated PCR, and nested PCR. The ufeII was determined to be a 906-bp cDNA
      containing an open reading frame of 795 bp encoding a putative protein of 264
      amino acids with a predicted molecular weight of 27.03 kDa. Besides, UFEII
      exhibited no hemorrhagic effect. Overall, U. unicinctus may represent a potential
      source of new therapeutic agents in thrombolytic therapy.

PMID- 23553103
TI  - Structural characteristics at the adductor muscle and shell interface in mussel.
AB  - The structure, organic matrix, and mineral structure of the scar (the interface
      between the adductor muscle and the shell) in Mytilus galloprovincialis were
      investigated. The scar was found to be a hierarchically multilayered structure
      composed of organic matrix and structurally different minerals. Different from
      the aragonite structure of the nacre, we have identified the top layer of the
      scar to contain structurally organized columnar calcite. This is the first report
      on calcite-containing scar. Study of the organic matrix showed that there was at
      least one protein that seemed to be preferentially localized in this columnar
      layer. Since the scar is the most important stress distribution site in the
      mussel, the function of the columnar structure and the matrix protein was
      discussed in relation to a similar structure at the tendon-bone connection site. 

PMID- 23553104
TI  - Central carbon metabolism in marine bacteria examined with a simplified assay for
      dehydrogenases.
AB  - A simplified assay platform was developed to measure the activities of the key
      oxidoreductases in central carbon metabolism of various marine bacteria. Based on
      microplate assay, the platform was low-cost and simplified by unifying the
      reaction conditions of enzymes including temperature, buffers, and ionic
      strength. The central carbon metabolism of 16 marine bacteria, involving
      Pseudomonas, Exiguobacterium, Marinobacter, Citreicella, and Novosphingobium were
      studied. Six key oxidoreductases of central carbon metabolism, glucose-6
      phosphate dehydrogenase, pyruvate dehydrogenase, 2-ketoglutarate dehydrogenase,
      malate dehydrogenase, malic enzyme, and isocitrate dehydrogenase were
      investigated by testing their activities in the pathway. High activity of malate
      dehydrogenase was found in Citreicella marina, and the specific activity achieved
      22 U/mg in cell crude extract. The results also suggested that there was a
      considerable variability on key enzymes' activities of central carbon metabolism
      in some strains which have close evolutionary relationship while they adapted to
      the requirements of the niche they (try to) occupy.

PMID- 23553105
TI  - Purification, sequencing, and biochemical characterization of a novel calcium
      independent alpha-amylase AmyTVE from Thermoactinomyces vulgaris.
AB  - alpha-Amylase from Thermoactinomyces vulgaris was highly purified 48.9-fold by
      ammonium sulfate precipitation, gel filtration on Sephadex G-50 column, and ion
      exchange chromatography column of DEAE-cellulose. The molecular weight of the
      enzyme was estimated to be 135 and 145 kDa by SDS-PAGE. Its high molecular weight
      is due to high glycosylation. The purified amylase exhibited maximal activity at
      pH 6.0 to 7.0 and was stable in the range of pH 4.0 to 9.0. The optimum
      temperature for its activity was 50  degrees C. The enzyme half-life time was 120
      min at 50  degrees C, suggesting intermediate temperature stable alpha-amylase.
      The enzyme was sensitive to different metal ions, including NaCl, CoCl(2), and
      CaCl(2), and to different concentrations of EDTA. The enzyme activity was
      inhibited in the presence of 1 mM CaCl(2), suggesting that it is a calcium
      independent alpha-amylase. The TLC showed that the amylase hydrolyzed starch to
      produce large maltooligosaccharides as the main products. A 1.1-kb DNA fragment
      of the putative alpha-amylase gene (amy TVE) from T. vulgaris was amplified by
      using two specific newly designed primers. Sequencing analysis showed 56.2 %
      similarity to other Thermoactinomyces alpha-amylases with two conserved active
      sites confirming its function.

PMID- 23553106
TI  - Cr(III) and Cr(VI) removal from aqueous solutions by cheaply available fruit
      waste and algal biomass.
AB  - This study compared the effectiveness of different biosorbents, viz. materials
      commonly present in natural treatment systems (Scenedesmus quadricauda and reed)
      and commonly produced fruit wastes (orange and banana peel) to remove Cr(III) and
      Cr(VI) from a synthetic wastewater simulating tannery wastewater. The Cr(III)
      removal efficiency followed the order S. quadricauda>orange peel>banana
      peel>reed, whereas the Cr(VI) removal followed the order banana peel>S.
      quadricauda>reed>orange peel. The chromium biosorption kinetics were governed by
      the intraparticle diffusion mechanism. Isotherm data obtained using the different
      biosorbents were fitted to the Langmuir, Freundlich, and SIPS models, revealing
      that the experimental data followed most closely the monolayer sorption theory
      based Langmuir model than the other models. The maximum Cr(III) sorption
      capacity, calculated using the Langmuir model, was found to be 12 and 9 mg/g for
      S. quadricauda and orange peel, respectively, and the maximum Cr(VI) sorption
      capacity calculated for banana peel was 3 mg/g. The influence of biosorbent size,
      pH, solid-liquid ratio, and competing ions were examined for Cr(III) biosorption
      by S. quadricauda and orange peel and for Cr(VI) sorption by banana peel. The
      solution pH was found to be the most influential parameter affecting the
      biosorption process: whereas pH 5 was found to be optimum for maximum removal of
      Cr(III), Cr(VI) was best removed at a pH as low as 3. Interference to chromium
      sorption by various ions revealed that Cr(III) binding onto orange peel occurs
      through electrostatic forces, whereas Cr(VI) binding onto banana peel through non
      electrostatic forces.

PMID- 23553107
TI  - Different responses to N(+) beam implantation between diploid and autotetraploid
      rice.
AB  - The objective of the study is to investigate the biological effects of N(+) beam
      implantation in different ploidy rice. N(+) beam implantation had increase effect
      in tillers number, spikelet fertility, grain yield per plant, si-phellem cell
      size, photosynthetic rate, transpiration rate, flag leaf dry weight, flag leaf
      culm dry weight, stomatal length, vascular bundle area, and protein and starch
      content and decrease effect in 1,000-grain weight, stomatal width and
      chlorophyll, calcium, sodium, and zinc content for all rice lines. N(+) beam
      implantation had opposite effect on diploid and autotetraploid rice lines in
      vascular bundle area, stomatal complexes areas, epidermal cell size, era length,
      area of air spaces, midrib length, papilla number, flag leaf length, flag leaf
      width, flag leaf area, and cadmium, copper, ferrum, magnesium and phosphorus
      content. Twenty traits of diploid line and ten traits of autotetraploid line are
      significantly increased by N(+) beam in this experiment, ranging from 6.8 to
      362.7 % in diploid line and 7.9 to 131.7 % in autotetraploid line. Six traits of
      diploid lines and 15 traits of autotetraploid line are significantly decreased by
      N(+) beam implantation in this experiment, ranging from 8.9 to 87.4 % in diploid
      line and 5.6 to 88.5 % in autotetraploid line.

PMID- 23553108
TI  - Effect of bovine serum albumin (BSA) on enzymatic cellulose hydrolysis.
AB  - Bovine serum albumin (BSA) was added to filter paper during the hydrolysis of
      cellulase. Adding BSA before the addition of the cellulase enhances enzyme
      activity in the solution, thereby increasing the conversion rate of cellulose.
      After 48 h of BSA treatment, the BSA adsorption quantities are 3.3, 4.6, 7.8,
      17.2, and 28.3 mg/g substrate, each with different initial BSA concentration
      treatments at 50  degrees C; in addition, more cellulase was adsorbed onto the
      filter paper at 50  degrees C compared with 35  degrees C. After 48 h of
      hydrolysis, the free-enzyme activity could not be measured without the BSA
      treatment, whereas the remaining activity of the filter paper activity was
      approximately 41 % when treated with 1.0 mg/mL BSA. Even after 96 h of
      hydrolysis, 25 % still remained. Meanwhile, after 48 h of incubation without
      substrate, the remaining enzyme activities were increased 20.7 % (from 43.7 to
      52.7 %) and 94.8 % (from 23.3 to 45.5 %) at 35 and 50  degrees C, respectively.
      Moreover, the effect of the BSA was more obvious at 35  degrees C compared with
      50  degrees C. When using 15 filter paper cellulase units per gram substrate
      cellulase loading at 50  degrees C, the cellulose conversion was increased from
      75 % (without BSA treatment) to >=90 % when using BSA dosages between 0.1 and 1.5
      mg/mL. Overall, these results suggest that there are promising strategies for BSA
      treatment in the reduction of enzyme requirements during the hydrolysis of
      cellulose.

PMID- 23553109
TI  - Production of ultra-high molecular weight poly-gamma-glutamic acid with Bacillus
      licheniformis P-104 and characterization of its flocculation properties.
AB  - A novel strain of Bacillus licheniformis P-104 was isolated from Chinese soybean
      paste to produce a bioflocculant. The bioflocculant was confirmed as ultra-high
      molecular weight poly-gamma-glutamic acid (gamma-PGA) using Fourier transform
      infrared spectrum, high-performance liquid chromatography, and gel permeation
      chromatography with multi-angle laser light scattering. The production technology
      and flocculation properties of gamma-PGA were investigated. By fed-batch
      fermentation in a 7-L bioreactor, the maximum gamma-PGA yield reached 41.6 g L(
      1) with a productivity rate of 1.07 g L(-1) h(-1). The flocculating activity of
      gamma-PGA for kaolin suspension was 33.5+/-1.6 1/OD under the optimized
      flocculation conditions (6 mM Ca(2+), 1.5 mg L(-1) gamma-PGA, and pH 6.0). The
      optimized dosage of gamma-PGA for flocculation was just about 30 % of that of
      reported gamma-PGA produced by other strains. Moreover, the flocculation activity
      of gamma-PGA produced by strain P-104 was much higher than commercial gamma-PGA
      with the molecular weight ranging 200-500 kDa and 1,500-2,500 kDa. This study
      provided a promising strain and an efficient method for production of ultra-high
      molecular weight gamma-PGA which could be used as a potential green
      bioflocculant.

PMID- 23553110
TI  - New analyses of the sensory organization test compared to the clinical test of
      sensory integration and balance in patients with benign paroxysmal positional
      vertigo.
AB  - OBJECTIVES/HYPOTHESIS: To determine whether the Sensory Organization Test (SOT)
      of the computerized dynamic posturography battery or the Clinical Test of Sensory
      Integration and Balance (CTSIB) is more likely to indicate balance disorders in
      people with benign paroxysmal positional vertigo (BPPV). STUDY DESIGN: Normal
      controls were compared to patients with unilateral BPPV of the posterior
      semicircular canal. METHODS: Subjects performed tests with eyes open or closed on
      stable and unstable surfaces, with head still or with head moving at 0.33 Hz in
      pitch or yaw. Dependent variables were the percent time of the standard duration
      each subject could perform the task, the number of head motions made, and
      kinematic variables measured with head- and torso-mounted inertial motion units.
      RESULTS: Because equilibrium scores of control subjects improved significantly
      over repeated trials on SOT, patients were given only one trial per condition.
      For percent time between-group differences were found on CTSIB with eyes closed,
      on foam, head moving in yaw showing significantly reduced performance by BPPV
      subjects compared to controls. Compared to controls, patients made significantly
      fewer head movements on CTSIB, eyes closed, on foam, head still, in pitch and
      yaw. Kinematic data also differed between the groups on tests with eyes closed
      and unstable surfaces with different head movement combinations, indicating
      increased instability in BPPV patients. CONCLUSIONS: For screening, CTSIB with
      head movements is more likely than SOT to indicate balance deficits, especially
      when dependent measures include percent time as well as head movement counts and
      kinematic measures.

PMID- 23553111
TI  - Autism risk across generations: a population-based study of advancing
      grandpaternal and paternal age.
AB  - IMPORTANCE: Advancing paternal age has been linked to autism. OBJECTIVE: To
      further expand knowledge about the association between paternal age and autism by
      studying the effect of grandfathers' age on childhood autism. DESIGN: Population
      based, multigenerational, case-control study. SETTING: Nationwide multigeneration
      and patient registers in Sweden. PARTICIPANTS: We conducted a study of
      individuals born in Sweden since 1932. Parental age at birth was obtained for
      more than 90% of the cohort. Grandparental age at the time of birth of the parent
      was obtained for a smaller subset (5936 cases and 30 923 controls). MAIN OUTCOME
      AND MEASURE: International Classification of Diseases diagnosis of childhood
      autism in the patient registry. RESULTS: A statistically significant monotonic
      association was found between advancing grandpaternal age at the time of birth of
      the parent and risk of autism in grandchildren. Men who had fathered a daughter
      when they were 50 years or older were 1.79 times (95% CI, 1.35-2.37; P < .001)
      more likely to have a grandchild with autism, and men who had fathered a son when
      they were 50 years or older were 1.67 times (95% CI, 1.35-2.37; P < .001) more
      likely to have a grandchild with autism, compared with men who had fathered
      children when they were 20 to 24 years old, after controlling for birth year and
      sex of the child, age of the spouse, family history of psychiatric disorders,
      highest family educational level, and residential county. A statistically
      significant monotonic association was also found between advancing paternal age
      and risk of autism in the offspring. Sensitivity analyses indicated that these
      findings were not the result of bias due to missing data on grandparental age.
      CONCLUSIONS AND RELEVANCE: Advanced grandparental age was associated with
      increased risk of autism, suggesting that risk of autism could develop over
      generations. The results are consistent with mutations and/or epigenetic
      alterations associated with advancing paternal age.

PMID- 23553112
TI  - Albusin B, mass-produced by the Saccharomyces cerevisiae suppression system,
      enhances lipid utilisation and antioxidant capacity in mice.
AB  - BACKGROUND: Albusin B (bacteriocin), isolated from Ruminococcus albus 7 and mass
      produced by the Saccharomyces cerevisiae expression system, has previously been
      shown to have a beneficial effect on lipid metabolism in broiler chickens. The
      present study was focused on the effect of albusin B on lipid metabolism in mice
      and the potential of albusin B-expressing yeast product (albusin B) as a food
      supplement. Forty-five BALB/c male mice at 6 weeks of age were each orally
      administered normal saline (control), yeast (0.125 mg kg(-1) ) or albusin B
      (0.125 mg kg(-1) ) for 14 days and then euthanised. RESULTS: Compared with the
      control group, albusin B-fed mice exhibited decreased body weight and plasma
      levels of triglycerides and free fatty acids but increased plasma high-density
      lipoprotein. Albusin B-fed mice showed higher mRNA expression of fatty acid
      oxidation in the ileum, heart and liver than control mice. Compared with the
      control treatment, both yeast and albusin B treatments caused a decrease in mRNA
      expression of fatty acid synthesis in the heart and liver. Moreover, albusin B
      suppressed mRNA levels of lipogenesis in the ileum and liver. Albusin B-fed mice
      exhibited more favourable adenosine triphosphate production and antioxidant
      capacity in the heart and liver. Albusin B treatment led to a significantly lower
      respiratory quotient than that of the control, whereas yeast treatment did not.
      CONCLUSION: This study demonstrated a beneficial effect of albusin B on lipid
      utilisation and anti-atherosclerotic and antioxidant capacities in mice. However,
      more comprehensive studies are required to elucidate the exact mechanism behind
      the effect of albusin B.

PMID- 23553114
TI  - Association between coronary collaterals and serum uric acid level in Chinese
      population with acute coronary syndrome.

PMID- 23553115
TI  - Does serum uric acid level affect coronary collaterals in patients with acute
      coronary syndrome?

PMID- 23553116
TI  - Fresh-stored osteochondral allografts for the treatment of femoral head defects:
      surgical technique and preliminary results.
AB  - PURPOSE: The purpose of this study was to present the preliminary clinical and
      radiographic outcomes of the treatment of femoral head osteochondral defects in
      eight consecutive symptomatic patients with fresh-stored osteochondral allografts
      via a trochanteric osteotomy. METHODS: This study included all consecutive
      patients treated in our department between 2008 and 2010 for worsening pain and
      mechanical symptoms of femoral head osteochondral defects. Each patient had
      preoperative routine hip radiographs and a preoperative magnetic resonance
      imaging study that determined and recorded the defect size and femoral head
      diameters. Allograft donors were identified through the Multiple Organ Retrieval
      and Exchange program (Ontario, Canada). RESULTS: The osteochondral defects were
      secondary to osteochondritis dissecans in four patients, avascular necrosis in
      three and femoral head fracture without dislocation in one. The patients' average
      age at surgery was 23.7 (range 17-42), and the average follow-up was 41 months
      (range 24-54). Follow-up included clinical and radiographic examinations at
      standard intervals. The average Harris hip scores improved from 57.7 (range 50
      65) points preoperatively to 83.9 (range 72-94) points at latest follow-up. Five
      patients had good-to-excellent clinical outcomes, and one had a fair outcome. One
      patient was converted to a total hip arthroplasty due to progression of
      arthritis. Another patient's graft subsided and he underwent a successful repeat
      transplantation. An additional patient required the removal of the screws
      transfixing her trochanter due to persistent irritation. CONCLUSIONS: These
      findings indicate that fresh-stored osteochondral allograft transplantation using
      a trochanteric slide and surgical dislocation is a viable treatment option for
      femoral head defects in young patients.

PMID- 23553117
TI  - Cement augmentation of the navigated iliosacral screw in the treatment of
      insufficiency fractures of the sacrum: a new method using modified implants.
AB  - PURPOSE: Pelvis ring fractures of geriatric patients are currently a serious
      problem in orthopedic and trauma surgery. One controversy that remains is the
      insufficiency fracture of the sacrum with treatment options ranging from
      conservative to operative. We modified standard 7.3-mm screws with additional
      perforations at the tip to allow cement injection trough the screw to improve
      implant anchorage. METHOD: We describe a new method of treatment of sacral
      insufficiency fractures. We use modified cannulated 7.3-mm screws (Synthes) with
      additional perforations at the screw tip. This allows the implant augmentation
      after proper implant positioning and contrast medium instillation for leakage
      detection. RESULTS: All patients (12 female) treated this way, are allowed to
      weight bear as tolerated immediately after surgery. The pain level (measured by
      the visual analog scale--VAS) was significantly reduced due to surgery (mean 8.2
      pre-operatively, mean 2.6 postoperatively), the pain medication could be reduced
      rapidly. CONCLUSION: The described procedure for the treatment of sacral
      insufficiency fractures has the potential to increase the safety of cement
      injection into the sacrum because of the possibility of contrast agent
      instillation prior to cement injection. Furthermore, the amount of cement can be
      reduced and additional stability can be attained due to iliosacral screw
      osteosynthesis compared to sacroplasty.

PMID- 23553118
TI  - Excessive femoral offset does not affect the range of motion after total hip
      arthroplasty.
AB  - PURPOSE: Implant dislocations are often caused by implant or bone impingement,
      and less impingement is critical to prevent dislocations. The aim of this study
      was to clarify the effect of the femoral offset in avoiding component or bony
      impingement after total hip arthroplasty (THA). METHODS: Seventy-eight patients
      underwent THA with a Pinnacle cup and Summit stem (DePuy). Intraoperative
      kinematic analysis was performed with a navigation system, which was used to
      obtain intraoperative range of motion (ROM) measurements during trial insertion
      of stems of two different offset lengths with the same head size. Further, ROM
      was also measured after actual component insertion. RESULTS: Maximal ROM was
      independent of the femoral offset of the stem in each patient. However, the range
      of external rotation was significantly greater in patients with a greater femoral
      offset. CONCLUSIONS: The Summit stem has enough offset length to avoid
      implant/bone impingement, even when the standard offset stem is used.
      Nevertheless, selection of the offset stem should be performed carefully to
      prevent offset complications.

PMID- 23553119
TI  - Long-term follow-up study of ingenol mebutate gel for the treatment of actinic
      keratoses.
AB  - IMPORTANCE: Ingenol mebutate is the active agent (a macrocyclic diterpene ester)
      in the sap of the plant Euphorbia peplus. This herb has been used as a
      traditional remedy for several different skin lesions, including skin cancers.
      OBJECTIVE: To assess 12-month recurrence rates and safety associated with ingenol
      mebutate gel treatment in patients who previously had achieved complete clearance
      of actinic keratoses. DESIGN AND SETTING: The treatment area was observed for
      recurrence for 12 months after the original study. Patients were treated in an
      outpatient setting. PARTICIPANTS: Patients received ingenol mebutate gel, 0.015%,
      daily for 3 consecutive days for actinic keratoses on the face or scalp or
      ingenol mebutate gel, 0.05%, daily for 2 consecutive days for actinic keratoses
      on the trunk or extremities. Study participants had achieved complete clearance
      in a prespecified 25-cm2 area at day 57 of their original trial. MAIN OUTCOME
      MEASURES: Recurrence rates and safety were assessed. RESULTS In total, 108
      patients with complete clearance of face or scalp lesions in the original trial
      and 76 patients with complete clearance of trunk or extremity lesions in the
      original trial were enrolled in the 12-month observational follow-up study. Of
      these, 100 patients (face or scalp) and 71 patients (trunk or extremities)
      completed all 12 months. The sustained lesion reduction rates compared with
      baseline were 87.2% for the face or scalp and 86.8% for the trunk or extremities.
      The estimated median times to recurrence were 365 days (face or scalp) and 274
      days (trunk or extremities). There were no safety concerns during the follow-up
      period. CONCLUSION AND RELEVANCE: Ingenol mebutate gel applied as field therapy
      for 2 or 3 consecutive days to treat actinic keratoses produced clinically
      relevant sustained clearance and long-term lesion reduction. TRIAL REGISTRATION
      clinicaltrials.gov Identifiers: NCT00953732, NCT00952783, and NCT00989313.

PMID- 23553120
TI  - Relevance of grade 1 gray-scale ultrasound findings in wrists and small joints to
      the assessment of subclinical synovitis in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the clinical relevance of grade 1 findings on gray
      scale ultrasound (GSUS) of the joints in patients with rheumatoid arthritis (RA).
      METHODS: We examined the wrists and small joints of 100 patients with early or
      established RA and 30 healthy controls, using GSUS and power Doppler ultrasound
      (PDUS). Independent clinical assessment of all joints for tenderness and swelling
      according to the European League Against Rheumatism examination technique was
      performed. Joints with grade 1 findings on GSUS were identified, and associations
      with swelling, pain, and findings on PDUS were assessed. Grade 1 findings on GSUS
      in patients with early RA were reassessed after 6 months of antirheumatic
      treatment. RESULTS: Grade 1 results represented the majority of all GSUS findings
      in patients with RA and were also frequently recorded in healthy controls. Grade
      1 GSUS findings were not associated with tenderness, swelling, or positive
      results on PDUS. In comparison to joints with grade 2 and grade 3 findings on
      GSUS, joints with grade 1 findings were less likely to respond to treatment.
      CONCLUSION: The present results indicate that grade 1 findings on GSUS have
      limited clinical relevance.

PMID- 23553121
TI  - The cognitive advantage for one's own name is not simply familiarity: an eye
      tracking study.
AB  - Eye-tracking technique and visual search task were employed to examine the
      cognitive advantage for one's own name and the possible effect of familiarity on
      this advantage. The results showed that fewer saccades and an earlier start time
      of first fixations on the target were associated with trials in which
      participants were asked to search for their own name, as compared to search for
      personally familiar or famous names. In addition, the results also demonstrated
      faster response times and higher accuracy in the former kind of trials. Taken
      together, these findings provide important evidence that one's own name has the
      potential to capture attention and that familiarity cannot account for this
      advantage. 

PMID- 23553122
TI  - The junction between hyaline cartilage and engineered cartilage in rabbits.
AB  - OBJECTIVES/HYPOTHESIS: Tracheoplasty using costal cartilage grafts to enlarge the
      tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic
      granulomatous tissue was observed at the edge of grafted costal cartilage. We
      investigated the junction between the native hyaline cartilage and the engineered
      cartilage plates that were generated by auricular chondrocytes for fabricating
      the airway. STUDY DESIGN: Controlled, prospecive study. METHODS: In group 1,
      costal cartilage from New Zealand white rabbits was collected and implanted into
      a space created in the cervical trachea. In group 2, chondrocytes from auricular
      cartilages were seeded on absorbable scaffolds. These constructs were implanted
      in the subcutaneous space. Engineered cartilage plates were then implanted into
      the trachea after 3 weeks of implantation of the constructs. The grafts in group
      1 and 2 were retrieved after 4 weeks. RESULTS: In group 1, histological studies
      of the junction between the native hyaline cartilage and the implanted costal
      cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the
      10 examined. In group 2, the junction between the native trachea and the
      engineered cartilage showed neocartilage tissue in nine anastomoses sides out of
      10. CONCLUSIONS: Engineered cartilage may be beneficial for engineered airways,
      based on the findings of the junction between the native and engineered grafts.

PMID- 23553123
TI  - Hearing loss with phosphodiesterase-5 inhibitors: a prospective and objective
      analysis with tadalafil.
AB  - OBJECTIVES/HYPOTHESIS: To assess the effect of tadalafil on auditory functions.
      STUDY DESIGN: Prospective observational study in a tertiary care hospital.
      METHODS: Twenty-five tadalafil naive patients with erectile dysfunction or
      pulmonary artery hypertension were subjected to pure-tone and brainstem-evoked
      response audiometry before drug therapy, and 3 and 30 days following drug
      therapy. Results were compared using analysis of variance for repeated measures
      with Bonferonni correction. RESULTS: Fifteen patients were taking tadalafil 10 mg
      for erectile dysfunction, and another 10 patients were on tadalafil 20 mg once
      daily for pulmonary artery hypertension. No statistically significant difference
      was found in hearing threshold at baseline and at follow-up (P > .05). However,
      three patients on tadalafil 20 mg showed a significant increase in hearing
      threshold at higher frequencies. There was no incidence of sudden sensorineural
      hearing loss in the study group. CONCLUSIONS: This is the first prospective and
      observational study that evaluated the effect of tadalafil on auditory functions
      with objective tests. Although there was no statistically significant result to
      confirm or refute the association between tadalafil and hearing impairment,
      increased threshold at higher frequencies after taking tadalafil supports the
      results from previous studies and hints at a possible relationship between the
      two. Similar large sample studies are warranted to know the exact association of
      phosphodiesterase-5 inhibitors on auditory functions.

PMID- 23553124
TI  - Mandatory continuing professional education in pharmacy: the Singapore
      experience.
AB  - BACKGROUND: Mandatory Continuing Professional Education (CPE) for the renewal of
      pharmacists' practising certificate was implemented in Singapore in 2008
      OBJECTIVE: To study pharmacists' perceptions and attitudes about the impact of
      mandatory CPE in Singapore. SETTING: Singapore. METHOD: Internet-based
      questionnaire survey, conducted between May and June 2011. MAIN OUTCOME MEASURE:
      Pharmacists' perceptions and attitudes toward mandatory CPE and the perceived
      difficulty in fulfilling the CPE requirements. RESULTS: The overall survey
      response rate was 52 % (840/1,609). Of the respondents, 32 % were non-practising,
      49 % were practising in patient care areas, and 19 % were practising in non
      patient care areas. More than half the pharmacists agreed that mandatory CPE (1)
      enhanced or increased their knowledge base and skills (70 %; 95 % CI 67-73 %),
      (2) motivated them to continually learn (64 %; 95 % CI, 60-67 %), and (3)
      motivated them to reflect on their professional practice or work (58 %; 95 % CI,
      54-61 %). Mandatory CPE was not perceived to enhance or increase employability.
      Non-practising pharmacists appeared to have the greatest difficulty meeting the
      CPE requirements. CONCLUSIONS: In general, pharmacists value mandatory CPE more
      for positive professional reasons than for employability reasons. The survey
      results may serve as useful baseline data for future studies of pharmacists'
      perceptions and attitudes toward CPE in Singapore.

PMID- 23553125
TI  - The assessment of the malignant mesothelioma cases and environmental asbestos
      exposure in Sivas province, Turkey.
AB  - One of the most significant diseases related to environmental asbestos exposure
      is malignant mesothelioma (MM). Sivas province is located in the Central Anatolia
      where asbestos exposure is common. We aimed to study clinical, demographical and
      epidemiologic features of the patients with MM in Sivas, along with the history
      of asbestos exposure. In total, 219 patients with MM who were diagnosed in our
      hospital between 1993 and 2010 were retrospectively analyzed in terms of
      demographical and clinical features. Rock, soil and house plaster samples were
      taken from the habitats of those patients and were evaluated with optical
      microscopy and X-ray diffraction methods. The age of the patients ranged between
      18 and 85 years. The male-to-female ratio was 1.4:1. Most of the patients
      confirmed an asbestos exposure history. The most frequent symptoms of the
      patients were chest pain (60 %) and dyspnea (50 %). The gap between the start of
      first symptoms and the diagnosis date was approximately 4 months in average. The
      plaster materials used in most of the houses were made up of mainly carbonate and
      silicate minerals and some chrysotile. Ophiolitic units contained fibrous
      minerals such as serpentine (clino + orthochrysotile) chiefly and pectolite,
      brucite, hydrotalcite and tremolite/actinolite in smaller amounts. MM is not
      primarily related to occupational asbestos exposure in our region, and hence,
      environmental asbestos exposure may be indicted. Yet, single or combined roles
      and/or interactions of other fibrous and non-fibrous minerals in the etiology of
      MM are not yet fully understood and remain to be investigated. 

PMID- 23553126
TI  - Polycyclic aromatic hydrocarbons and organochlorine pesticides in rice hull from
      a typical e-waste recycling area in southeast China: temporal trend, source, and
      exposure assessment.
AB  - The residue levels of 16 US EPA priority polycyclic aromatic hydrocarbons (PAHs)
      and 16 selected organochlorine pesticides (OCPs) in rice and rice hull collected
      from a typical e-waste recycling area in southeast China were investigated from
      2005 to 2007. PAHs and OCPs also were measured in ten mollusk species (soft
      tissues) collected in an adjacent bay in 2007. Individual PAHs were frequently
      found in the entire sample set (including the rice, hull, and mollusk samples)
      with a detection rate of 73 %. The total concentrations of 16 PAHs (SigmaPAHs)
      and 16 OCPs (SigmaOCPs) were in the range of 40.8-432 ng/g dry weight (mean: 171
      ng/g) and 2.35-925 ng/g (122 ng/g), respectively, which were comparable or higher
      than those reported in some polluted areas. Statistical comparisons suggested
      that the concentrations of contaminants in hull gradually decreased from 2005 to
      2007 and the residue levels were generally in the order of mollusk, hull, and
      rice, on a dry weight basis. Principal component analysis in combination with
      diagnostic ratios implied that combustion of coal, wood, and plastic wastes that
      are closely associated with crude e-waste recycling activities is the main source
      of PAHs. The finding of decreasing trend of concentrations of PAHs in this area
      is consistent with the efforts of local authorities to strengthen regulations on
      illegal e-waste recycling activities. Composition analysis suggested that there
      is a recent usage or discharge of hexachlorocyclohexane and
      dichlorodiphenyltrichloroethane into the tested area. The estimated daily intake
      (EDI) of SigmaPAHs and SigmaOCPs (calculated from mean concentrations) through
      rice and mollusk consumption was 0.411 and 0.921 MUg/kg body weight (bw)/day,
      respectively. 

PMID- 23553127
TI  - A ticking clock links metabolic pathways and organ systems function in health and
      disease.
AB  - Rhythmic variations with 24-h periodicity hallmark homeostatic regulation,
      metabolic processes and organ systems function, driven by a circadian timing
      system composed of central and peripheral oscillators. Recent reports suggest
      that disrupted circadian rhythmicity of physiology and behavior severely alters
      body homeostasis. Nuclear receptors and transcriptional regulators sense hormonal
      and metabolic cues and manage the rhythmic patterns of chromatin remodelling and
      gene expression, playing a key role in the cross talk between the circadian clock
      circuitry, the metabolic pathways and the organ systems. The alteration of this
      cross talk contributes to the pathophysiology of metabolic, degenerative, immune
      related and neoplastic diseases. 

PMID- 23553128
TI  - Serum prolidase activity in psoriasis patients.
AB  - This study aimed to evaluate serum prolidase activity and the effects of gender,
      body mass index (BMI), disease severity and duration, and therapy type on
      prolidase activity in patients with psoriatic as well as the relationship between
      serum NO. and prolidase levels in these patients. The study included 29
      clinically documented plaque patients with psoriasis and 24 healthy volunteers.
      Data such as age, sex, BMI, duration and severity of disease, and type of therapy
      were assessed. NO. levels were determined by the Griess reaction. Serum prolidase
      assay is based on a colorimetric determination of proline by Chinard's reagent.
      We did not determine any difference in serum NO. levels of psoriatic patients
      when compared to controls. Serum prolidase levels in psoriasis patients were
      significantly higher than those in controls. There was no significant difference
      in prolidase activity between male and female. No statistically significant
      correlations were found between serum prolidase levels and BMI, PASI and disease
      duration. When compared between topical treatment group and systemic treatment
      group, there was no significant difference in serum prolidase activity. In
      conclusion, patients with psoriasis exhibit higher serum prolidase activity
      independent of gender, BMI, disease severity or duration, type of treatments or
      NO. level. However, further studies are needed to verify these findings as well
      as altered collagen synthesis in patients with psoriasis. 

PMID- 23553131
TI  - Molecular mechanisms of neuropathological changes in Alzheimer's disease: a
      review.
AB  - More than 100 years after description of Alzheimer's disease (AD), two major
      pathological processes observed already by Alois Alzheimer, remain as the main
      explanation of the pathogenesis of Alzheimer's disease. Important molecular
      interactions leading to AD neuropathology were described in amyloid cascade and
      in tau protein function. No clinical trials with novel therapies based on amyloid
      cascade and tau protein hypotheses have been successful. The main aim of recent
      research is focused on the question what is primary mechanism leading to the
      molecular development of AD pathology. Promising explanation of triggering
      mechanism can be seen in vascular pathology that have direct influence on the
      development of pathological processes typical for Alzheimer disease. Novel
      insight into a number of cellular signaling mechanisms, as well as mitochondrial
      function in Alzheimer disease could also bring explanations of initial processes
      leading to the development of this pathology.

PMID- 23553132
TI  - Effects of aspartame metabolites on astrocytes and neurons.
AB  - Aspartame, a widespread sweetener used in many food products, is considered as a
      highly hazardous compound. Aspartame was discovered in 1965 and raises a lot of
      controversy up to date. Astrocytes are glial cells, the presence and functions of
      which are closely connected with the central nervous system (CNS). The aim of
      this article is to demonstrate the direct and indirect role of astrocytes
      participating in the harmful effects of aspartame metabolites on neurons. The
      artificial sweetener is broken down into phenylalanine (50%), aspartic acid (40%)
      and methanol (10%) during metabolism in the body. The excess of phenylalanine
      blocks the transport of important amino acids to the brain contributing to
      reduced levels of dopamine and serotonin. Astrocytes directly affect the
      transport of this amino acid and also indirectly by modulation of carriers in the
      endothelium. Aspartic acid at high concentrations is a toxin that causes
      hyperexcitability of neurons and is also a precursor of other excitatory amino
      acid - glutamates. Their excess in quantity and lack of astrocytic uptake induces
      excitotoxicity and leads to the degeneration of astrocytes and neurons. The
      methanol metabolites cause CNS depression, vision disorders and other symptoms
      leading ultimately to metabolic acidosis and coma. Astrocytes do not play a
      significant role in methanol poisoning due to a permanent consumption of large
      amounts of aspartame. Despite intense speculations about the carcinogenicity of
      aspartame, the latest studies show that its metabolite - diketopiperazine - is
      cancirogenic in the CNS. It contributes to the formation of tumors in the CNS
      such as gliomas, medulloblastomas and meningiomas. Glial cells are the main
      source of tumors, which can be caused inter alia by the sweetener in the brain.
      On the one hand the action of astrocytes during aspartame poisoning may be
      advantageous for neuro-protection while on the other it may intensify the
      destruction of neurons. The role of the glia in the pathogenesis of many CNS
      diseases is crucial.

PMID- 23553133
TI  - Spatial relationships between diffuse prion protein deposits and neuronal
      perikarya in variant Creutzfeldt-Jakob disease.
AB  - Two morphological types of prion protein (PrPsc) deposit occur in the cerebral
      cortex of cases of variant Creutzfeldt-Jakob disease (vCJD), viz., diffuse and
      florid deposits. The objective of this study was to determine whether diffuse
      type PrPsc deposits in areas of the cerebral cortex in six cases of the variant
      form of CJD (vCJD) were spatially correlated with neurons and whether diffuse
      deposit size was related to the number of adjacent neurons contributing PrPsc. In
      cortical gyri, density of surviving neurons was 5.38-12.15 per 50 * 200 um sample
      field, neurons being distributed randomly, regularly or were clustered relative
      to the pia mater. Density of neurons embedded within diffuse deposits, however,
      was three to eight times their overall density in the section. In addition,
      diffuse deposit area was positively correlated with the number of embedded
      neurons. The frequency distribution of diffuse deposits with 0, 1, 2, 3, ..., n,
      embedded neurons did not deviate from a Poisson distribution. These results
      suggest: (1) diffuse deposits in vCJD develop in situ as a result of the
      formation of PrPsc in relation to clusters of neurons, (2) size of a diffuse
      deposit is determined by the number of adjacent neurons which develop PrPsc, and
      (3) the probability that PrPsc is formed in relation to one neuron is independent
      of that of its neighbour.

PMID- 23553134
TI  - Loss of genetic material within 1p and 19q chromosomal arms in low grade gliomas
      of central nervous system.
AB  - Diffuse gliomas can constitute up to one third of all gliomas diagnosed in
      neurosurgical centers. Their invasive growth, progression to more malignant
      lesions, and the lack of standardized management guidelines render a significant
      clinical problem. The discovery of 1p and 19q chromosomal arms deletion in
      neoplastic cells will probably influence both more objective diagnosis and more
      accurate prediction of chemotherapy response. Defining the above mentioned
      deletion is becoming a standard procedure in Western European countries and in
      the USA when LGG is diagnosed. As a result an attempt has been made to detect
      deletion using fluorescence in situ hybridization and to determine its prognostic
      value. Genetic material from 34 grade II gliomas was examined. Separate 1p and
      19q deletions were discovered in 14 and 16 cases respectively. Simultaneous
      occurrence of both was observed in 12. The frequency of occurrence of
      simultaneous deletions 1p and 19q varied based on histopathological diagnosis.
      This disorder was not observed in astrocytomas, in oligoastrocytomas it appeared
      in 50% cases. The highest incidence of deletion was noted in oligodendrogliomas
      and amounted to 66.7%, p < 0.005. Median survival in patients with diagnosed 1p
      and 19q deletion in their neoplastic cells is twice longer in comparison with
      patients in whom no such deletion was observed (80 months vs. 41 months, p <
      0.05). Frontal location of a tumor occurred to be a statistically significant
      factor unfavorable for prognosis, p < 0.05. In the work presented the
      fluorescence in situ hybridization was successfully applied to identify deletion
      1p/19q. Its incidence depends on the type of diagnosed glioma. Deletions also
      have prognostic significance in the test group what constitutes the basis for
      inclusion of determining deletion 1p/19q into diagnostic and treatment algorithm
      in LGGs.

PMID- 23553135
TI  - High resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of
      surviving C6 glioma cells after X-ray irradiation.
AB  - PURPOSE: To study biochemical response of living model of glioma to X-rays
      irradiation using high resolution proton nuclear magnetic resonance (1H NMR)
      spectroscopy. MATERIAL AND METHODS: Rat glioma C6 cells were irradiated with 3.8
      Gy (D0, the 37% clonogenic survival dose) of X-rays from a teletherapy unit at
      the dose rate 8.8 Gy/min. After irradiation the cells were incubated at 37
      degrees C/5%CO2/95%O2 for various period of incubation (24, 48, 72 and 96 hours)
      in the fresh medium. The high resolution 1H NMR spectra of the agarose-cell
      mixtures (2 x 10(7) cells/ml) were acquired using a Varian Inova-300 multinuclear
      pulsed NMR spectrometer operating at the 1H resonance frequency of 300 MHz. The
      mean spectra were obtained as the averages of six independent measurements.
      RESULTS: The statistically significant increase in the CH2/CH3 lipid signals
      ratio in the C6 cells after irradiation with 3.8 Gy dose and incubation for 24-96
      h was observed. CONCLUSIONS: Our method of the sample preparation enables the
      metabolic effects of irradiation to be observed in viable cells, which can
      effectively support the identification of the spectroscopic changes in vivo.
      Application of the gel suspensions in the NMR studies has advantages over the
      usual liquid suspensions in terms of improved reproducibility of the data and
      cell viability, with no net loss of the spectral quality.

PMID- 23553136
TI  - Influence of serum and albumin on the in vitro anandamide cytotoxicity toward C6
      glioma cells assessed by the MTT cell viability assay: implications for the
      methodology of the MTT tests.
AB  - Anandamide (AEA), an endogenous ligand of cannabinoid CB1 and CB2 receptors,
      which also binds transient receptor potential vanilloid type 1 receptor (TRPV1),
      has been shown to display substantial selective cytotoxicity toward some cancer
      cell lines in vitro, although the relevant data are not consistent. In the
      present study, we employed the MTT test to assess short-term cytotoxicity of AEA
      on C6 rat glioma cell culture. When anandamide was administered to the culture
      medium with foetal bovine serum (FBS), no cytotoxic effect was observed following
      24 h exposure of the glioma cells to micromolar concentrations of AEA. However,
      if no serum was present in the medium, micro-to-submicromolar concentrations of
      AEA induced dose-dependent cytotoxicity clearly detectable after 24 h. Control
      experiments made it possible to exclude significant interference of serum with
      the MTT test per se. Bovine serum albumin mimicked the effect of FBS. We conclude
      that the apparent inhibition of short-term cytotoxicity of AEA toward C6 rat
      glioma cells in vitro is caused by binding AEA to serum proteins such as albumin.
      Taking into account that blood serum or albumin is practically always present in
      cell culture media, we discuss implications of binding substances to serum
      proteins for methodology and interpretation of in vitro cytotoxicity testing.

PMID- 23553137
TI  - Suppression of the lipid peroxidation process in the CNS reduces neurological
      expression of experimentally induced autoimmune encephalomyelitis.
AB  - OBJECTIVE: Here we report the influence of malondialdehyde (MDA) as a measure of
      the lipid peroxidation process (LP), on multiple sclerosis (MS) pathogenesis and
      its neurological signs, during the treatment with aminoguanidine (AG) - a
      selective inducible nitric oxide synthase inhibitor and N-Acetyl cysteine (NAC) -
      an oxidative scavenger, in the experimental autoimmune encephalomyelitis (EAE),
      an animal model for studying MS. MATERIAL AND METHODS: Encephalomyelitis
      induction by the subcutaneous injection of myelin basic protein of bovine type,
      dissolved in phosphate buffered saline (PBS) emulsified in equal volume of the
      complete Freund's adjuvant (CFA), was described in detail in our earlier
      published papers. Each of animals was randomly assigned to seven groups - control
      (PBS), EAE, CFA, EAE + AG, AG, EAE + NAC and NAC group. In each animal, the
      development of neurological signs of EAE was scored, these results were published
      earlier. MDA was evaluated in the central nervous system (CNS) structure -
      cerebellums and spinal cords. RESULTS: The obtained results show that the AG and
      NAC treatment significantly reduces the MDA level in both examined tissues (p <
      0.05) ameliorating at the same time EAE clinical signs (p < 0.05). CONCLUSIONS:
      Taking together our present and earlier findings we conclude that LP may provoke
      and promote MS, while blocking of this process results in amelioration of the
      clinical onset and disease activity. These results may be useful as a new insight
      into mechanisms and potential targets for therapeutic strategies in MS.

PMID- 23553138
TI  - Evaluation of oxidative and nitrosative stress in relapsing remitting multiple
      sclerosis: effect of corticosteroid therapy.
AB  - This study is designed to evaluate the roles of oxidative and nitrosative stress
      in serum and cerebrospinal fluid (CSF) of relapsing remitting multiple sclerosis
      (RRMS) patients. Oxidative stress markers thiobarbituric acid reactive substances
      (TBARS), 8-epi-PGF2alpha, conjugated diene and nitrosative stress markers
      nitrotyrosine, nitrit-nitrate were analysed in serum and CSF of 20 newly
      diagnosed RRMS patients before and after methyl prednysolone (MP) therapy (1000
      mg/day i.v., for 5 days) and in healthy control group.TBARS and conjugated diene
      were analysed spectrophotometrically, nitrite-nitrate fluorometrically, 8-epi
      PGF2alpha and nitrotyrosine were measured by ELISA. Serum conjugated diene (p <
      0.001) and 8-epi-PGF2alpha (p < 0.05) levels were significantly higher in RRMS
      patients before MP therapy with respect to control group. MP therapy caused a
      significant decrease only in 8-epi-PGF2alpha level (p < 0.05). Serum
      nitrotyrosine levels were significantly lower in RRMS patients both before (p <
      0.001) and after (p < 0.001) MP therapy with respect to controls. Serum nitrite
      nitrate levels were significantly lower (p < 0.05) in RRMS patients before
      therapy compared to controls. Nitrotyrosine and nitrite-nitrate levels in CSF of
      RRMS patients were significantly higher (p < 0.001) before therapy compared to
      normal pressure hydrocephalia control group. Our findings reveal increased
      oxidative stress in serum of RRMS patients and the benefical role of MP therapy
      in relieving oxidative stress.As to nitrosative stress, nitrotyrosine and nitrite
      nitrate levels were increased in CSF and decreased in serum.

PMID- 23553139
TI  - A transcript coding for a partially duplicated form of alpha7 nicotinic
      acetylcholine receptor is absent from the CD4+ T-lymphocytes of patients with
      autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
AB  - INTRODUCTION: It has been suggested that the homomer-forming alpha7 subunit
      (CHRNA7) of the neuronal nicotinic acetylcholine receptor (nAChR) is involved in
      the pathogenesis of common idiopathic generalized epilepsies (IGEs), whereas
      mutations of the gene coding for the alpha4 nAChR subunit (CHRNA4) are associated
      with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Several genes
      encoding nAChR subunits, including a partially duplicated isoform of CHRNA7
      (CHRFAM7A), are expressed in peripheral blood lymphocytes (PBLs), and are
      constituents of peripheral receptors corresponding to nAChRs in the brain.
      Moreover, a 2-bp deletion polymorphism (c.497-498delTG; rs67158670), resulting in
      a frame shift and truncation of the protein product of the gene, has been found
      in the CHRFAM7A gene and is associated with some neurological diseases. AIM OF
      THE STUDY: CHRFAM7A transcript levels in CD4+ T-lymphocytes were compared between
      ADNFLE patients harbouring the c.851C>T mutation of the CHRNA4 gene and control
      healthy individuals in order to determine whether there is any correlation
      between CHRFAM7A expression in CD4+ T-lymphocytes and the severity of epileptic
      symptoms. We also tested the hypothesis that the 2-bp deletion polymorphism in
      the partially duplicated alpha7 nAChR gene may be related to ADNFLE in these
      patients. MATERIAL AND METHODS: Peripheral venous blood samples were collected
      from 3 individuals with ADNFLE and from 10 healthy individuals. From the isolated
      CD4+ T-lymphocytes, RNA was prepared and the CHRFAM7A transcript level was
      determined by RT-qPCR. In order to compare the CHRNA7 and CHRFAM7A sequences and
      genotype the -2bp polymorphism, genomic DNA was prepared from PBLs. RESULTS: It
      has been demonstrated that CHRFAM7A is expressed in CD4+ T-lymphocytes of healthy
      individuals, the relative abundance of the transcript being nearly equal (about
      100 copies per cell), but it is not expressed in ADNFLE patients. Genotype
      analysis showed that the -2bp polymorphism was found in all patients as well as
      in seven healthy individuals. CONCLUSIONS: Our observations confirm the
      hypothesis that the CHRFAM7A gene is expressed in CD4+ T-lymphocytes of healthy
      individuals and that this expression is legitimate. The observed lack of CHRFAM7A
      expression in ADNFLE patients might be an important factor in the pathogenesis of
      ADNFLE.

PMID- 23553140
TI  - Prenatal exposure of diclofenac sodium affects morphology but not axon number of
      the median nerve of rats.
AB  - The present study examined the effect of DS exposure on median nerve development
      in rats during prenatal life. Pregnant female rats were divided into three
      groups: a control group, a saline group and a DS group. Offspring of these
      animals were divided into 2 subgroups: 4 weeks old and 20 weeks old. Nerve
      samples were taken from the right legs and evaluated using stereological
      techniques in terms of the axon number, axon cross-sectional area, and myelin
      thickness. No drug-dependent macroscopic abnormality was observed in the nerve.
      No differences were noted for axon number in the control, saline, and DS groups
      of the same age and gender. No gender difference was found for axon number or
      axon area between the other matched groups. In conclusion, prenatal exposure to
      diclofenac sodium does not affect axon number in rats, but can alter the
      morphology of the male and female median nerve.

PMID- 23553141
TI  - Pseudo-stroke manifestation of multiple myeloma: a report of two cases with
      literature review.
AB  - Multiple myeloma rarely presents with neurological symptoms. We describe two
      patients with pseudo-stroke manifestation of multiple myeloma. The first patient
      was a 60-year-old female with the initial presentation of multiple myeloma
      forming a large skull tumour compressing the brain with resultant symptoms of
      aphasia, limited logical contact and right upper extremity paresis. The second
      patient was a 69-year-old female who presented with a partial motor epileptic
      seizure involving both right limbs with persisting weakness of muscles and speech
      disturbances due to a skull tumour 4 years after the diagnosis of multiple
      myeloma. Pseudo-stroke manifestation of multiple myeloma is extremely uncommon,
      however it can sometimes be observed both as an initial presentation and in the
      course of long-lasting disease.

PMID- 23553142
TI  - Neuroprotective effects of paeoniflorin: an emerging concept in neurology.

PMID- 23553143
TI  - Influenza vaccines: time for a rethink.
AB  - Officials and professional societies treat influenza as a major public health
      threat for which the annual vaccine offers a safe and effective solution. In this
      article, I challenge these basic assumptions. I show that there is no good
      evidence that vaccines reduce serious complications of influenza, the outcomes
      the policy is meant to address. Moreover, promotional messages conflate
      "influenza" (disease caused by influenza viruses) with "flu" (a syndrome with
      many causes, of which influenza viruses appear to be a minor contributor). This
      lack of precision causes physicians and potential vaccine recipients to have
      unrealistic assumptions about the vaccine's potential benefit, and impedes
      dissemination of the evidence on nonpharmaceutical interventions against
      respiratory diseases. In addition, there are potential vaccine-related harms, as
      unexpected and serious adverse effects of influenza vaccines have occurred. I
      argue that decisions surrounding influenza vaccines need to include a discussion
      of these risks and benefits.

PMID- 23553144
TI  - Body mass index, lifetime smoking intensity and lung cancer risk.
AB  - There is as yet no generally accepted explanation for the common finding that low
      body mass index (BMI) is associated with an increased risk of lung cancer. We
      investigated this association in a Canadian population-based case-control study
      (1996-2002) with a particular view to assessing the hypothesis that the observed
      association was due to residual confounding by smoking. Analyses were based on
      1,076 cases and 1,439 controls who provided their height at enrollment and their
      weight at two points in time, at age 20 and 2 years before enrollment. BMI, in
      kg/m(2) , was classified into underweight (<18.5), normal (18.5-24.9), overweight
      (25.0-29.9), and obese (>=30). Smoking history was synthesized into a
      comprehensive smoking index (CSI) that integrated duration, intensity and time
      since quitting. Odds ratios (ORs) and 95% confidence intervals (CIs) for BMI-lung
      cancer associations were estimated, adjusting for CSI as well as several
      sociodemographic, lifestyle and occupational factors. The normal BMI category was
      used as the reference. Among those who were underweight at age 20, there was a
      lower risk of lung cancer (OR = 0.69, 95% CI: 0.50-0.95). Conversely, lung cancer
      risk was increased among those who were underweight 2 years before enrollment (OR
      = 2.30, 95% CI: 1.30-4.10). The results were almost identical when stratifying
      analyses based on smoking history into never/lighter and heavier smokers. The
      inverse association between recent BMI and lung cancer is unlikely to be largely
      attributable to residual confounding by smoking. Reverse causality or a true
      relationship between BMI and lung cancer remain plausible. 

PMID- 23553145
TI  - Surface properties and corrosion behavior of Co-Cr alloy fabricated with
      selective laser melting technique.
AB  - We sought to study the corrosion behavior and surface properties of a commercial
      cobalt-chromium (Co-Cr) alloy which was fabricated with selective laser melting
      (SLM) technique. For this purpose, specimens were fabricated using different
      techniques, such as SLM system and casting methods. Surface hardness testing,
      microstructure observation, surface analysis using X-ray photoelectron
      spectroscopy (XPS) and electrochemical corrosion test were carried out to
      evaluate the corrosion properties and surface properties of the specimens. We
      found that microstructure of SLM specimens was more homogeneous than that of cast
      specimens. The mean surface hardness values of SLM and cast specimens were 458.3
      and 384.8, respectively; SLM specimens showed higher values than cast ones in
      hardness. Both specimens exhibited no differences in their electrochemical
      corrosion properties in the artificial saliva through potentiodynamic curves and
      EIS, and no significant difference via XPS. Therefore, we concluded that within
      the scope of this study, SLM-fabricated restorations revealed good surface
      properties, such as proper hardness, homogeneous microstructure, and also showed
      sufficient corrosion resistance which could meet the needs of dental clinics. 

PMID- 23553146
TI  - A resting-state functional magnetic resonance imaging study of acute carbon
      monoxide poisoning in humans.
AB  - The objective of this study was to evaluate the brain function characteristics of
      carbon monoxide poisoning patients using resting-state functional magnetic
      resonance imaging (fMRI) method. For this purpose, 12 carbon monoxide poisoning
      patients and healthy controls were subjected to resting-state fMRI scans
      separately. A regional homogeneity (ReHo) approach was used to analyze the brain
      function in carbon monoxide poisoning patients. Compared with control group, the
      value of ReHo in carbon monoxide poisoning group showed distinct decrease in
      bilateral superior frontal gyrus, middle frontal gyrus, right cuneus, left middle
      temporal gyrus, right insula, and cerebellum. Therefore, it was concluded that
      the brain functions in carbon monoxide poisoning patients were abnormal under the
      resting-state. The cuneate lobe function may indicate the degree of brain hypoxia
      and strengthening the cerebellar function training may promote the rehabilitation
      process. 

PMID- 23553147
TI  - Improvement in the detection of locoregional recurrence in head and neck
      malignancies: F-18 fluorodeoxyglucose-positron emission tomography/computed
      tomography compared to high-resolution contrast-enhanced computed tomography and
      endoscopic examination.
AB  - OBJECTIVES/HYPOTHESIS: To compare the diagnostic efficacy of positron emission
      tomography (PET) with F-18 fluorodeoxyglucose (FDG-PET)/computed tomography (CT)
      to that of contrast-enhanced high-resolution CT (HRCT) and assess the value of a
      combinatorial approach in detection of recurrent squamous cell cancer of the head
      and neck (HNC) and to assess the efficacy of FDG-PET/CT with and without HRCT in
      comparison to standard-of-care follow-up--physical examination (PE) and endoscopy
      (E)--in determination of locally recurrent HNC. STUDY DESIGN: Retrospective
      study. METHODS: A total of 103 patients with HNC underwent FDG-PET/CT and neck
      HRCT. There were two groups of patients: Group A had an FDG-PET study acquired
      with low-dose CT, and group B had an FDG-PET study acquired with HRCT. The PET
      data obtained with or without HRCT were compared on a lesion and patient basis
      with the results of the PE/E. RESULTS: On a lesion basis, both groups combined
      had higher sensitivity and negative predictive value (NPV) than the HRCT.
      Specificity and positive predictive value (PPV) for group B were higher than for
      group A. On a patient basis, both groups combined had a higher sensitivity and
      NPV than PE/E, respectively, although specificity of PE/E was higher than that of
      either group. PET data obtained with either protocol directly influenced
      treatment. CONCLUSIONS: HRCT increases the specificity and PPV of PET/CT when
      acquired simultaneously with PET. FDG-PET/CT acquired with either LDCT or HRCT
      has higher accuracy than HRCT alone and increases the sensitivity and NPV of
      PE/E.

PMID- 23553148
TI  - Postoperative neuroleptic malignant syndrome-like symptoms improved with
      intravenous diazepam: a case report.
AB  - A 75-year-old man who had undergone left upper lobectomy of the lung exhibited
      fever and insomnia on postoperative day (POD) 1 and muscle rigidity, autonomic
      instability, and somnolence on POD2 after epidural administration of droperidol
      and withdrawal of oral etizolam. He had not been known to have any neuromuscular
      diseases or psychiatric diseases, with the exception of anxiety disorder. Brain
      computed tomography did not show cerebrovascular disorders. Consultation with a
      neurologist led to a suspicion of neuroleptic malignant syndrome (NMS). Epidural
      droperidol was stopped and administration of dantrolene was initiated. These
      measures, in addition to supportive care, only partially ameliorated the symptoms
      of the patient, and consciousness disturbance developed; the patient finally
      became comatose on POD3. However, intravenous diazepam (10 mg) improved his
      symptoms abruptly. Subsequently, oral administration of lorazepam (1 mg/day) was
      started, and his symptoms disappeared within 2 days (POD5). Although NMS-like
      symptoms are rarely seen in clinical practice, some factors may induce it during
      the perioperative period, such as the administration of dopamine antagonists and
      the cessation of benzodiazepines. Intravenous diazepam is an effective treatment
      in cases with suspected gamma-aminobutyric acid (GABA) hypoactivity at the
      GABA(A) receptor induced by the cessation of benzodiazepines.

PMID- 23553150
TI  - [Emergency room management : in the era of the White Paper, S3 guidelines,
      Advanced Trauma Life Support(r) and TraumaNetwork DGU(r) of the German Society of
      Trauma Surgery].
AB  - The treatment of the severely injured is, just as the injury severity and
      combinations, often highly complex and leaves little leeway for delay, dissent or
      even error. In order to reduce this to a minimum, trained emergency room teams in
      addition to optimal technical and structural prerequisites are necessary. This
      must function in an interdisciplinary fashion according to fixed consensus
      algorithms which are known to all team members and have been agreed by all
      participants. The White Paper on treatment of the severely injured of the German
      Society of Trauma Surgery (DGU) and the recently published S3 guidelines offer
      evidence-based recommendations on the structural, technical, organizational and
      personnel prerequisites.

PMID- 23553149
TI  - Association of maternal exposure to childhood abuse with elevated risk for autism
      in offspring.
AB  - IMPORTANCE: Adverse perinatal circumstances have been associated with increased
      risk for autism in offspring. Women exposed to childhood abuse experience more
      adverse perinatal circumstances than women unexposed, but whether maternal abuse
      is associated with autism in offspring is unknown. OBJECTIVES: To determine
      whether maternal exposure to childhood abuse is associated with risk for autism
      in offspring and whether possible increased risk is accounted for by a higher
      prevalence of adverse perinatal circumstances among abused women, including
      toxemia, low birth weight, gestational diabetes, previous induced abortion,
      intimate partner abuse, pregnancy length shorter than 37 weeks, selective
      serotonin reuptake inhibitor use, and alcohol use and smoking during pregnancy.
      DESIGN AND SETTING: Nurses' Health Study II, a population-based longitudinal
      cohort of 116 430 women. PARTICIPANTS: Nurses with data on maternal childhood
      abuse and child's autism status (97.0% were of white race/ethnicity). Controls
      were randomly selected from among children of women who did not report autism in
      offspring (participants included 451 mothers of children with autism and 52 498
      mothers of children without autism). MAIN OUTCOME MEASURES: Autism spectrum
      disorder in offspring, assessed by maternal report and validated with the Autism
      Diagnostic Interview-Revised in a subsample. RESULTS: Exposure to abuse was
      associated with increased risk for autism in children in a monotonically
      increasing fashion. The highest level of abuse was associated with the greatest
      prevalence of autism (1.8% vs 0.7% among women not abused, P = .005) and with the
      greatest risk for autism adjusted for demographic factors (risk ratio, 3.7; 95%
      CI, 2.3-5.8). All adverse perinatal circumstances except low birth weight were
      more prevalent among women abused in childhood. Adjusted for perinatal factors,
      the association of maternal childhood abuse with autism in offspring was slightly
      attenuated (risk ratio for highest level of abuse, 3.0; 95% CI, 1.9-4.8).
      CONCLUSIONS AND RELEVANCE: We identify an intergenerational association between
      maternal exposure to childhood abuse and risk for autism in the subsequent
      generation. Adverse perinatal circumstances accounted for only a small portion of
      this increased risk.

PMID- 23553151
TI  - Vascular function and atherosclerosis progression after 1 y of flavonoid intake
      in statin-treated postmenopausal women with type 2 diabetes: a double-blind
      randomized controlled trial.
AB  - BACKGROUND: In healthy participants, short-term flavan-3-ol and isoflavone
      intakes improve vascular function; however, the potential combined benefit of
      these compounds on atherosclerosis progression remains unclear for those at
      elevated risk of cardiovascular disease. OBJECTIVE: The objective was to examine
      whether combined isoflavone and flavan-3-ol intake alters vascular function in
      postmenopausal women with type 2 diabetes mellitus (T2DM). DESIGN: A double
      blind, parallel-design, placebo-controlled 1-y trial was conducted in
      postmenopausal T2DM patients randomly assigned to a split dose of 27 g flavonoid
      enriched chocolate/d [850 mg flavan-3-ols (90 mg epicatechin) + 100 mg
      isoflavones (aglycone equivalents)/d] or matched placebo. Intima-media thickness
      of the common carotid artery (CCA-IMT), pulse wave velocity (PWV), augmentation
      index, blood pressure (BP), and vascular biomarkers were assessed. RESULTS: A
      total of 93 patients completed the trial. Overall, the flavonoid intervention did
      not significantly change CCA-IMT, augmentation index, or BP, but pulse pressure
      variability improved (flavonoid: -0.11 +/- 0.07 mm Hg/min; placebo: 0.10 +/- 0.11
      mm Hg/min; P = 0.04). In a subgroup with PWV data, net improvements were observed
      [flavonoid (n = 18): -0.07 +/- 0.38 m/s; placebo (n = 17): 0.68 +/- 0.25 m/s; P =
      0.01], which equated to a 10% CV risk reduction. Equol producers (n = 17) had
      larger reductions in diastolic BP, mean arterial pressure, and PWV (-2.24 +/-
      1.31 mm Hg, -1.24 +/- 1.30 mm Hg, and -0.68 +/- 0.40 m/s, respectively; P < 0.01)
      compared with non-equol producers (n = 30). CONCLUSIONS: Although the 1-y
      intervention did not change CCA-IMT or BP, clinically relevant improvements in
      arterial stiffness were observed; equol producers were particularly responsive.
      Flavonoids may augment existing therapeutic strategies to reduce cardiovascular
      disease risk in postmenopausal T2DM patients, and longer studies are needed to
      examine the effects on atherosclerosis progression. This trial was registered at
      clinicaltrials.gov as NCT00677599.

PMID- 23553153
TI  - The USDA Automated Multiple-Pass Method accurately assesses population sodium
      intakes.
AB  - BACKGROUND: Given current sodium-reduction strategies, accurate and practical
      methods to monitor sodium intake in the US population are critical. Although the
      gold standard for estimating sodium intake is the 24-h urine collection, few
      studies have used this biomarker to evaluate the accuracy of a dietary
      instrument. OBJECTIVE: Our objective was to compare self-reported dietary intake
      of sodium with 24-h urinary excretion obtained in the USDA Automated Multiple
      Pass Method (AMPM) Validation Study. DESIGN: Subjects were healthy, weight-stable
      volunteers aged 30-69 y recruited from the Washington, DC, area. Data from 465
      subjects who completed at least one 24-h recall and collected a complete 24-h
      urine sample during the same period were used to assess the validity of sodium
      intake. Reporting accuracy was calculated as the ratio of reported sodium intake
      to that estimated from the urinary biomarker (24-h urinary sodium/0.86).
      Estimations of sodium intake included salt added in cooking but did not include
      salt added at the table. RESULTS: Overall, the mean (95% CI) reporting accuracy
      was 0.93 (0.89, 0.97) for men (n = 232) and 0.90 (0.87, 0.94) for women (n =
      233). Reporting accuracy was highest for subjects classified as normal weight
      [body mass index (in kg/m(2)) <25]: 1.06 (1.00, 1.12) for men (n = 84) and 0.99
      (0.94, 1.04) for women (n = 115). For women only, reporting accuracy was higher
      in those aged 50-69 y than in those who were younger. CONCLUSION: Findings from
      this study suggest that the USDA AMPM is a valid measure for estimating sodium
      intake in adults at the population or group level.

PMID- 23553152
TI  - Decreased dietary fiber intake and structural alteration of gut microbiota in
      patients with advanced colorectal adenoma.
AB  - BACKGROUND: Accumulating evidence indicates that diet is one of the most
      important environmental factors involved in the progression from advanced
      colorectal adenoma (A-CRA) to colorectal cancer. OBJECTIVE: We evaluated the
      possible effects of dietary fiber on the fecal microbiota of patients with A-CRA.
      DESIGN: Patients with a diagnosis of A-CRA by pathological examination were
      enrolled in the A-CRA group. Patients with no obvious abnormalities or
      histopathological changes were enrolled in the healthy control (HC) group.
      Dietary fiber intake was assessed in all patients. Short-chain fatty acids
      (SCFAs) in feces were detected by gas chromatography. The fecal microbiota
      community was analyzed by 454 pyrosequencing based on 16S ribosomal RNA. RESULTS:
      Lower dietary fiber patterns and consistently lower SCFA production were observed
      in the A-CRA group (n = 344). Principal component analysis showed distinct
      differences in the fecal microbiota communities of the 2 groups. Clostridium,
      Roseburia, and Eubacterium spp. were significantly less prevalent in the A-CRA
      group (n = 47) than in the HC group (n = 47), whereas Enterococcus and
      Streptococcus spp. were more prevalent in the A-CRA group (n = 47) (all P <
      0.05). Butyrate and butyrate-producing bacteria were more prevalent in a subgroup
      of HC subjects with a high fiber intake than in those in both the low-fiber HC
      subgroup and the high-fiber A-CRA subgroup (all P < 0.05). CONCLUSION: A high
      fiber dietary pattern and subsequent consistent production of SCFAs and healthy
      gut microbiota are associated with a reduced risk of A-CRA. This trial was
      registered at www.chictr.org as ChiCTR-TRC-00000123.

PMID- 23553154
TI  - Black tea lowers the rate of blood pressure variation: a randomized controlled
      trial.
AB  - BACKGROUND: Measures of blood pressure variation have been associated with
      cardiovascular disease and related outcomes. The regular consumption of black tea
      can lower blood pressure, but its effects on blood pressure variation have yet to
      be investigated. OBJECTIVE: We aimed to assess the effects of black tea
      consumption on the rate of ambulatory blood pressure variation. DESIGN: Men and
      women (n = 111) with systolic blood pressure between 115 and 150 mm Hg at
      screening were recruited in a randomized, controlled, double-blind, 6-mo parallel
      designed trial designed primarily to assess effects on blood pressure.
      Participants consumed 3 cups/d of either powdered black tea solids (tea) or a
      flavonoid-free caffeine-matched beverage (control). The 24-h ambulatory blood
      pressure level and rate of measurement-to-measurement blood pressure variation
      were assessed at baseline, day 1, and 3 and 6 mo. RESULTS: Across the 3 time
      points, tea, compared with the control, resulted in lower rates of systolic (P =
      0.0045) and diastolic (P = 0.016) blood pressure variation by ~10% during
      nighttime (2200-0600). These effects, which were immediate at day 1 and sustained
      over 6 mo, were independent of the level of blood pressure and heart rate. The
      rate of blood pressure variation was not significantly altered during daytime
      (0800-2000). CONCLUSIONS: These findings indicate that a component of black tea
      solids, other than caffeine, can influence the rate of blood pressure variation
      during nighttime. Thus, small dietary changes have the potential to significantly
      influence the rate of blood pressure variation. This trial was registered at the
      Australian New Zealand Clinical Trials Registry as ACTR12607000543482.

PMID- 23553155
TI  - Intake of trans fat and all-cause mortality in the Reasons for Geographical and
      Racial Differences in Stroke (REGARDS) cohort.
AB  - BACKGROUND: A high intake of trans fatty acids decreases HDL cholesterol and is
      associated with increased LDL cholesterol, inflammation, diabetes, cancer, and
      mortality from cardiovascular disease. The relation between trans fat intake and
      all-cause mortality has not been established. OBJECTIVE: The aim of this study
      was to determine the relation between trans fat intake and all-cause mortality.
      DESIGN: We used data from the Reasons for Geographic and Racial Differences in
      Stroke (REGARDS) study-a prospective cohort study of white and black men and
      women residing in the continental United States. Energy-adjusted trans fat intake
      was categorized into quintiles, and Cox-regression was used to evaluate the
      association between trans fat intake and all-cause mortality. RESULTS: During 7 y
      of follow-up, there were 1572 deaths in 18,513 participants included in REGARDS.
      From the first to the fifth quintile of trans fat intake, the mortality rates per
      1000 person-years of follow-up (95% CIs) were 12.8 (11.3, 14.5), 14.3 (12.7,
      16.2), 14.6 (13.0, 16.5), 19.0 (17.1, 21.1), and 23.6 (21.5, 25.9), respectively.
      After adjustment for demographic factors, education, and risk factors for
      mortality, the HRs (95% CIs) for all-cause mortality were 1.00, 1.03 (0.86,
      1.23), 0.98 (0.82, 1.17), 1.25 (1.05, 1.48), and 1.24 (1.05, 1.48), respectively
      (P-trend = 0.004). The population attributable risk due to trans fat intake was
      7% (95% CI: 5%, 8%). CONCLUSION: Higher trans fat intake is associated with an
      increased risk of all-cause mortality.

PMID- 23553156
TI  - REG1B as a predictor of childhood stunting in Bangladesh and Peru.
AB  - BACKGROUND: Undernutrition remains a significant problem worldwide, with
      environmental enteropathy implicated as a contributing factor. An understanding
      of the pathogenesis and identification of children at risk are critical to the
      design of more-effective interventions. OBJECTIVE: The stool regenerating gene
      1beta (REG1B) protein, which is a putative measure of intestinal injury and
      repair, was tested as a noninvasive biomarker of future childhood stunting.
      DESIGN: A total of 222 children from Bangladesh and 97 children from Peru, who
      were from impoverished communities, were followed from birth through 24 mo of age
      with anthropometric measures obtained every 3 mo. Stool REG1B protein
      concentrations were obtained by using an REG1B polyclonal-polyclonal ELISA at 3
      mo of age. We tested for the ability of REG1B to forecast future anthropometric
      shortfalls, independent of known predictors of undernutrition of family income
      and baseline height and weight. RESULTS: In the Bangladesh cohort of 222
      children, higher REG1B concentrations at month 3 were significantly and
      independently associated with a growth shortfall in a linear regression analysis
      at months 9, 12, 18, 21, and 24 and, in the Peru cohort, at months 12, 15, 18,
      21, and 24. With the use of a mixed model for repeated measurements, higher stool
      REG1B concentrations at 3 mo were also independently predictive of a lower future
      length-for-age z score through 24 mo of age (Bangladesh P = 0.006; Peru P =
      0.058). CONCLUSION: The ability of fecal REG1B to predict growth shortfall in
      independent cohorts of impoverished children from the developing world offers
      promise as a malnutrition biomarker and supports a role for environmental
      enteropathy in the pathogenesis of growth shortfall.

PMID- 23553157
TI  - Magnesium retention from metabolic-balance studies in female adolescents: impact
      of race, dietary salt, and calcium.
AB  - BACKGROUND: Previously, we showed that black girls retained more calcium than
      white girls did and that salt loading negatively affected calcium retention.
      Racial differences likely exist in other bone minerals also, such as magnesium,
      in response to salt loading during growth. OBJECTIVE: We studied racial
      differences in magnesium metabolism in response to dietary sodium and calcium
      during rapid bone growth. DESIGN: Twenty-seven white and 40 black girls (11-15 y
      old) were studied for 3 wk while they consumed low-sodium (1.3 g/d) and high
      sodium (3.8 g/d) diets by using a randomized-order, crossover metabolic study
      with 3 dietary calcium intakes; the magnesium dietary intake was fixed at 230
      mg/d. Urine and feces were collected during each 3-wk period in 24-h pools and
      analyzed for magnesium. A mixed-model ANOVA was used to determine the effect of
      race and dietary sodium with calcium intake as a covariate. RESULTS: Salt loading
      or calcium intake had no significant effect on urinary magnesium excretion.
      Blacks excreted significantly less urinary magnesium (mean +/- SD: 83.8 +/- 25.6
      mg/d) than did whites (94.9 +/- 27.3 mg/d; P < 0.05). No effects were observed in
      fecal magnesium excretion. Magnesium retention was higher with the low-sodium
      diet (50.1 +/- 44.0 mg/d) than with the high-sodium diet (39.3 +/- 49.8 mg/d) (P
      < 0.05), with no effects of race or calcium intake. Salt loading had no effect on
      biomarkers. Whites had higher 25-hydroxyvitamin D and insulin-like growth factor
      binding protein 3 but lower 1,25-dihydroxyvitamin D and parathyroid hormone
      concentrations. CONCLUSIONS: Blacks excreted less urinary magnesium than did
      whites. Magnesium retention was similar between races but higher with the low
      sodium diet. Kinetic studies are needed to fully explain magnesium homeostasis.
      This trial was registered at clinicaltrials.gov as NCT01564238.

PMID- 23553158
TI  - Physical activity intensity, sedentary time, and body composition in
      preschoolers.
AB  - BACKGROUND: Detailed associations between physical activity (PA) subcomponents,
      sedentary time, and body composition in preschoolers remain unclear. OBJECTIVE:
      We examined the magnitude of associations between objectively measured PA
      subcomponents and sedentary time with body composition in 4-y-old children.
      DESIGN: We conducted a cross-sectional study in 398 preschool children recruited
      from the Southampton Women's Survey. PA was measured by using accelerometry, and
      body composition was measured by using dual-energy X-ray absorptiometry.
      Associations between light physical activity, moderate physical activity (MPA),
      vigorous physical activity (VPA), and moderate-to-vigorous physical activity
      (MVPA) intensity; sedentary time; and body composition were analyzed by using
      repeated-measures linear regression with adjustment for age, sex, birth weight,
      maternal education, maternal BMI, smoking during pregnancy, and sleep duration.
      Sedentary time and PA were also mutually adjusted for one another to determine
      whether they were independently related to adiposity. RESULTS: VPA was the only
      intensity of PA to exhibit strong inverse associations with both total adiposity
      [P < 0.001 for percentage of body fat and fat mass index (FMI)] and abdominal
      adiposity (P = 0.002 for trunk FMI). MVPA was inversely associated with total
      adiposity (P = 0.018 for percentage of body fat; P = 0.022 for FMI) but only
      because of the contribution of VPA, because MPA was unrelated to fatness (P >=
      0.077). No associations were shown between the time spent sedentary and body
      composition (P >= 0.11). CONCLUSIONS: In preschoolers, the time spent in VPA is
      strongly and independently associated with lower adiposity. In contrast, the time
      spent sedentary and in low-to-moderate-intensity PA was unrelated to adiposity.
      These results indicate that efforts to challenge pediatric obesity may benefit
      from prioritizing VPA.

PMID- 23553159
TI  - An increase in renal dopamine does not stimulate natriuresis after fava bean
      ingestion.
AB  - BACKGROUND: Fava beans (Vicia faba) contain dihydroxyphenylalanine (dopa), and
      their ingestion may increase dopamine stores. Renal dopamine regulates blood
      pressure and blood volume via a natriuretic effect. OBJECTIVE: The objective was
      to determine the relation between dietary fava beans, plasma and urinary
      catechols, and urinary sodium excretion in 13 healthy volunteers. DESIGN:
      Catechol and sodium data were compared by using a longitudinal design in which
      all participants consumed a fixed-sodium study diet on day 1 and the fixed-sodium
      diet plus fava beans on day 2. Blood was sampled at 1, 2, 4, and 6 h after a
      meal, and 3 consecutive 4-h urine samples were collected. RESULTS: Mean (+/-SD)
      plasma dopa was significantly greater 1 h after fava bean consumption (11,670 +/-
      5440 compared with 1705 +/- 530 pg/mL; P = 0.001) and remained elevated at 6 h.
      Plasma dopamine increased nearly 15-fold during this period. Fava bean
      consumption also increased urinary dopamine excretion to 306 +/- 116, 360 +/-
      235, and 159 +/- 111 MUg/4-h urine sample compared with 45 +/- 21, 54 +/- 29, and
      44 +/- 17 MUg in the 3 consecutive 4-h samples after the control diet (P <=
      0.005). These substantial increases in plasma and urinary dopa and dopamine were
      unexpectedly associated with decreased urinary sodium. CONCLUSION: The failure of
      fava bean consumption to provoke natriuresis may indicate that dopa
      concentrations in commercially available beans do not raise renal dopamine
      sufficiently to stimulate sodium excretion, at least when beans are added to a
      moderate-sodium diet in healthy volunteers. This trial was registered at
      clinicaltrials.gov as NCT01064739.

PMID- 23553160
TI  - Fruit, Mediterranean-style, and high-fat and -sugar diets are associated with the
      risk of night sweats and hot flushes in midlife: results from a prospective
      cohort study.
AB  - BACKGROUND: Diet has been suggested to be a potential risk factor for vasomotor
      menopausal symptoms (VMSs), ie, hot flushes and night sweats. OBJECTIVE: We
      investigated the associations between dietary patterns and risk of VMSs by using
      data from middle-aged women born between 1946 and 1951 in the Australian
      Longitudinal Study on Women's Health. DESIGN: A prospective cohort study of 6040
      women with a natural menopause were followed up at 3-y intervals over 9 y.
      Dietary intake was assessed at baseline in 2001, and the presence of VMSs was
      assessed at baseline and follow-up. Factor analysis and generalized estimating
      equation models for binary repeated measures were performed. RESULTS: Six dietary
      patterns were identified from factor analysis: cooked vegetables, fruit,
      Mediterranean style, meat and processed meat, dairy, and high fat and sugar. A
      higher consumption of the fruit or Mediterranean-style diet was inversely
      associated with VMSs in a comparison of the top with the bottom quintile, with
      adjusted ORs of 0.81 (95% CI: 0.71, 0.93; P-trend = 0.0009) and 0.80 (95% CI:
      0.69, 0.92; P-trend = 0.0004), respectively. The high-fat and -sugar pattern
      increased the risk of VMSs in a comparison of the top with the bottom quintile,
      with an adjusted OR of 1.23 (95% CI: 1.05, 1.44; P-trend = 0.02). CONCLUSIONS:
      Consumption of a fruit or Mediterranean-style diet decreased the risk of
      reporting VMSs, whereas consumption of a high-fat and -sugar diet increased the
      risk of VMSs. These results may eventually lead to a basis for the development of
      dietary preventive measures for VMSs.

PMID- 23553161
TI  - Comparison of gestational weight gain-related pregnancy outcomes in American
      primiparous and multiparous women.
AB  - BACKGROUND: In Danish data, the tradeoffs between mother and infant in the risks
      of adverse pregnancy outcomes were reached at lower gestational weight gain (GWG)
      among multiparous than among primiparous women. It is unknown whether the same
      difference exists among American women. OBJECTIVE: The objective was to determine
      whether these tradeoffs also differ by parity among women in a contemporary
      American birth cohort. DESIGN: Data from 822 primiparous and 2055 multiparous
      American women who participated in the Infant Feeding Practices Study II (2005
      2007), a national cohort study, were analyzed. Their self-reported GWG was
      divided into 4 categories (<=10, >10 to <15, 15 to <20, and >=20 kg). GWG
      specific absolute adjusted risks for emergency cesarean delivery, birth of a
      small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infant, and
      postpartum weight retention at 6 mo were estimated by multiple logistic
      regression analyses for women in 3 categories of prepregnancy body mass index.
      RESULTS: Primiparous women gained more weight during pregnancy than did
      multiparous women (mean +/- SD: 15.9 +/- 6.9 compared with 13.5 +/- 6.2 kg; P <
      0.0001). The absolute adjusted risk of postpartum weight retention rose steeply
      with increasing GWG among both primiparous and multiparous women. The risk of
      emergency cesarean delivery and of delivering LGA infants increased with
      increasing GWG only among multiparous women. The risk of SGA tended to decrease
      with increasing GWG in both parity groups. CONCLUSION: These findings extend the
      concept of a lower optimal GWG among multiparous than primiparous women to
      American women.

PMID- 23553162
TI  - Association of raw fruit and fruit juice consumption with blood pressure: the
      INTERMAP Study.
AB  - BACKGROUND: Epidemiologic evidence suggests that fruit consumption may lower the
      risk of cardiovascular diseases through blood pressure (BP)-lowering effects;
      little is known on the independent effect of raw fruit and fruit juice on BP.
      OBJECTIVE: The objective was to quantify associations of raw fruit and fruit
      juice consumption with BP by using cross-sectional data from the INTERnational
      study on MAcro/micronutrients and blood Pressure (INTERMAP) of 4680 men and women
      aged 40-59 y from Japan, China, the United Kingdom, and the United States.
      DESIGN: During 4 visits, 8 BP, four 24-h dietary recalls, and two 24-h urine
      samples were collected. Country-specific multivariate-controlled linear
      regression coefficients, including adjustment for urinary sodium excretion, were
      estimated and pooled, weighted by inverse of their variance. RESULTS: The average
      total raw fruit consumption varied from a mean +/- SD of 52 +/- 65 g/1000 kcal in
      the United States to 68 +/- 70 g/1000 kcal in China. Individual raw fruit intake
      was not associated with BP in pooled analyses for all countries or in
      participants from Western countries, although a positive association with
      diastolic BP was observed in East Asian participants (per 50 g/1000 kcal; 0.37 mm
      Hg; 95% CI: 0.02, 0.71). Positive relationships with diastolic BP were found for
      citrus fruit intake in Western consumers (per 25 g/1000 kcal; 0.47 mm Hg; 95% CI:
      0.12, 0.81) and for apple intake in East Asian consumers (0.40 mm Hg; 95% CI:
      0.03, 0.78). Among East Asian banana consumers, banana intake was inversely
      associated with diastolic BP (-1.01 mm Hg; 95% CI: -1.88, -0.02). Fruit juice
      intake, which was negligible in Asia, was not related to BP in Western countries.
      CONCLUSION: Consistent associations were not found between raw fruit and fruit
      juice consumption of individuals and BP. This observational study was registered
      at www.clinicaltrials.gov as NCT00005271.

PMID- 23553163
TI  - Critical windows for nutritional interventions against stunting.
AB  - An analysis of early growth patterns in children from 54 resource-poor countries
      in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score
      during the first 2 y of life and no recovery until >=5 y of age. This finding has
      focused attention on the period -9 to 24 mo as a window of opportunity for
      interventions against stunting and has garnered considerable political backing
      for investment targeted at the first 1000 d. These important initiatives should
      not be undermined, but the objective of this study was to counteract the growing
      impression that interventions outside of this period cannot be effective. We
      illustrate our arguments using longitudinal data from the Consortium of Health
      Oriented Research in Transitioning collaboration (Brazil, Guatemala, India,
      Philippines, and South Africa) and our own cross-sectional and longitudinal
      growth data from rural Gambia. We show that substantial height catch-up occurs
      between 24 mo and midchildhood and again between midchildhood and adulthood, even
      in the absence of any interventions. Longitudinal growth data from rural Gambia
      also illustrate that an extended pubertal growth phase allows very considerable
      height recovery, especially in girls during adolescence. In light of the critical
      importance of maternal stature to her children's health, our arguments are a
      reminder of the importance of the more comprehensive UNICEF/Sub-Committee on
      Nutrition Through the Life-Cycle approach. In particular, we argue that
      adolescence represents an additional window of opportunity during which
      substantial life cycle and intergenerational effects can be accrued. The
      regulation of such growth is complex and may be affected by nutritional
      interventions imposed many years previously.

PMID- 23553164
TI  - Dietary disinhibition modulates neural valuation of food in the fed and fasted
      states.
AB  - BACKGROUND: Dietary disinhibition is a behavioral trait associated with weight
      gain and obesity. Because food choices are made according to the relative value
      assigned to each option, examination of valuation signals through functional
      magnetic resonance imaging (fMRI) may elucidate the neural basis for the
      association between dietary disinhibition and weight gain. OBJECTIVE: We examined
      how food valuation signals differ in the fed and fasted states between persons
      with high dietary disinhibition (HD) and low dietary disinhibition (LD). DESIGN:
      Sixteen men with HD and 14 with LD underwent fMRI once while fasted and once
      after being fed in a counterbalanced order. In-scanner preference to consume a
      test food relative to a neutral-tasting, neutral-health reference food was
      examined. The slope of magnetic resonance signal change corresponding to these
      food preferences constituted the food valuation signal that was compared across
      disinhibition group and satiety state. RESULTS: Both the HD and LD participants
      reported being less hungry (F(1,28) = 113.11, P < 0.001) after being fed than
      when fasted. However, food valuation signals in the ventromedial prefrontal
      cortex (vmPFC) differed between the groups (F(1,28) = 21.34, P < 0.001). Although
      LD participants showed attenuated vmPFC activity after being fed (t(13) = 4.11, P
      < 0.001), HD participants showed greater vmPFC activity in the fed than in the
      fasted state (t(15) = -2.56, P < 0.05). CONCLUSIONS: Despite reporting normal
      decreases in hunger ratings after being fed, persons with HD have an altered
      neural valuation of food. This may be a mechanism underlying their propensity to
      overeat and gain weight. This trial was registered at clinicaltrials.gov as
      NCT00988819.

PMID- 23553165
TI  - Data imputation for accelerometer-measured physical activity: the combined
      approach.
AB  - BACKGROUND: Accelerometers are gaining popularity for the assessment of the
      physical activity level; however, compliance is a problem that results in missing
      data. Data from study days in which the accelerometer is not worn for a number of
      hours that are sufficient to reach a predetermined cutoff value are considered
      invalid and discarded. The problem of missing data is commonly handled by
      imputation; however, all traditional imputation methods ignore the available
      information from invalid days. OBJECTIVE: In this study, I propose a new approach
      to the imputation of missing accelerometer data that takes into account the data
      available from invalid days. DESIGN: A total of 4069 participants in NHANES waves
      2003-2004 and 2005-2006 who provided 7 d of valid accelerometer data were used to
      illustrate this new approach. The method of imputation was a combined approach
      that combined the available data from valid days and invalid days to impute
      missing values. Simulation studies were carried out to compare this new combined
      approach with the traditional imputation method for 1) accuracy and 2) effect
      size estimation of the sex-physical activity relation by using the root mean
      squared error (RMSE). RESULTS: The combined approach performed significantly
      better than traditional imputation method (all t tests P < 0.001), with the
      percentage reduction of the RMSE for accuracy and effect-size estimation that
      ranged from 12.4% to 17.3% and 19.8% to 32.9%, respectively. CONCLUSION: The
      combined approach significantly outperforms the traditional imputation algorithm.

PMID- 23553167
TI  - Dietary calcium intake and risk of stroke: a dose-response meta-analysis.
AB  - BACKGROUND: The findings from epidemiologic studies of calcium intake and risk of
      stroke have been conflicting. OBJECTIVE: The objective was to conduct a dose
      response meta-analysis of prospective studies to assess the association between
      dietary calcium intake and stroke risk. DESIGN: Relevant studies were identified
      by searching PubMed and EMBASE databases until 11 December 2012 and by reviewing
      the reference lists of relevant articles. Observational prospective studies that
      reported RRs and 95% CIs for the association of calcium intake with stroke
      incidence or mortality were eligible. Study-specific RRs were combined by using a
      random-effects model. RESULTS: Eleven prospective studies, including 9095 cases
      of stroke, were included in the meta-analysis. Evidence of a nonlinear
      association between dietary calcium intake and risk of stroke was found. In a
      stratified analysis, calcium intake was inversely associated with risk of stroke
      in populations with a low to moderate average calcium intake (<700 mg/d; RR for a
      300-mg/d increase in calcium intake: 0.82; 95% CI: 0.76, 0.88) but was weakly
      positively associated with risk in populations with a high calcium intake (>=700
      mg/d; corresponding RR: 1.03; 95% CI: 1.01, 1.06). An inverse association between
      calcium intake and risk of stroke was observed only in Asian populations (n = 4;
      RR for a 300-mg/d increase in calcium intake: 0.78; 95% CI: 0.71, 0.87).
      CONCLUSION: These findings suggest that dietary calcium intake may be inversely
      associated with stroke in populations with low to moderate calcium intakes and in
      Asian populations.

PMID- 23553166
TI  - Adherence to the World Cancer Research Fund/American Institute for Cancer
      Research guidelines and risk of death in Europe: results from the European
      Prospective Investigation into Nutrition and Cancer cohort study1,4.
AB  - BACKGROUND: In 2007, the World Cancer Research Fund (WCRF) and the American
      Institute for Cancer Research (AICR) issued recommendations on diet, physical
      activity, and weight management for cancer prevention on the basis of the most
      comprehensive collection of available evidence. OBJECTIVE: We investigated
      whether concordance with WCRF/AICR recommendations is related to risk of death.
      DESIGN: The current study included 378,864 participants from 9 European countries
      enrolled in the European Prospective Investigation into Cancer and Nutrition
      study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle
      information was collected. A WCRF/AICR score, which incorporated 6 of the
      WCRF/AICR recommendations for men [regarding body fatness, physical activity,
      foods and drinks that promote weight gain, plant foods, animal foods, and
      alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women
      [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated
      greater concordance with WCRF/AICR recommendations. Associations between the
      WCRF/AICR score and risks of total and cause-specific death were estimated by
      using Cox regression analysis. RESULTS: After a median follow-up time of 12.8 y,
      23,828 deaths were identified. Participants within the highest category of the
      WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard
      of death (95% CI: 0.59, 0.75) compared with participants within the lowest
      category of the WCRF/AICR score (0-2 points in men; 0-3 points in women).
      Significant inverse associations were observed in all countries. The WCRF/AICR
      score was also significantly associated with a lower hazard of dying from cancer,
      circulatory disease, and respiratory disease. CONCLUSION: Results of this study
      suggest that following WCRF/AICR recommendations could significantly increase
      longevity.

PMID- 23553168
TI  - Dietary patterns and risk of dementia in an elderly Japanese population: the
      Hisayama Study.
AB  - BACKGROUND: To our knowledge, there are no previous reports that assessed the
      association between dietary patterns and risk of dementia in Asian populations.
      OBJECTIVE: We investigated dietary patterns and their potential association with
      risk of incident dementia in a general Japanese population. DESIGN: A total of
      1006 community-dwelling Japanese subjects without dementia, aged 60-79 y, were
      followed up for a median of 15 y. The reduced rank regression procedure was used
      to efficiently determine their dietary patterns. Estimated risk conferred by a
      particular dietary pattern on the development of dementia was computed by using a
      Cox proportional hazards model. RESULTS: Seven dietary patterns were extracted;
      of these, dietary pattern 1 was correlated with high intakes of soybeans and
      soybean products, vegetables, algae, and milk and dairy products and a low intake
      of rice. During the follow-up, 271 subjects developed all-cause dementia. Of
      these individuals, 144 subjects had Alzheimer disease (AD), and 88 subjects had
      vascular dementia (VaD). After adjustment for potential confounders, risks of
      development of all-cause dementia, AD, and VaD were reduced by 0.66 (95% CI:
      0.46, 0.95), 0.65 (95% CI: 0.40, 1.06), and 0.45 (95% CI: 0.22, 0.91),
      respectively, in subjects in the highest quartile of score for dietary pattern 1
      compared with subjects in the lowest quartile. CONCLUSION: Our findings suggest
      that a higher adherence to a dietary pattern characterized by a high intake of
      soybeans and soybean products, vegetables, algae, and milk and dairy products and
      a low intake of rice is associated with reduced risk of dementia in the general
      Japanese population.

PMID- 23553169
TI  - Factors predicting overweight in US kindergartners.
AB  - BACKGROUND: Childhood overweight is a substantial public-health problem, but
      little is known about predictors of early childhood overweight. OBJECTIVE: We
      aimed to identify factors--alone and in combination--that predict kindergarten
      overweight. DESIGN: We analyzed nationally representative data from the Early
      Childhood Longitudinal Study-Birth Cohort, a longitudinal cohort study of 6800
      children followed from birth through kindergarten. Multivariable logistic
      regression and recursive partitioning analysis (RPA) were performed to identify
      individual and clusters of parental, prenatal/pregnancy, infant, and toddler
      factors predicting kindergarten overweight. The main outcome was kindergarten
      overweight [body mass index (BMI) >=85th percentile, which includes obesity].
      RESULTS: The prevalence of kindergarten overweight was 32%. By using combinations
      (derived from 131 factors) of a weight-for-length or BMI >=85th percentile at
      earlier ages, race/ethnicity, a maternal gestational diabetes history, birth
      weight, and ages at solid-food introduction and the child pulling to a stand, the
      RPA identified 6 groups with a particularly high prevalence of kindergarten
      overweight (56-100%) and 2 groups with a particularly low prevalence (11-15%). An
      especially high prevalence was noted for children with a >=85th BMI percentile at
      preschool age (77%) and in children with a >=85th BMI percentile at 2 y old, for
      white children whose mother had gestational diabetes (100%), and for minority
      children with a birth weight <2695.5 g and who pulled themselves to a stand at
      <7.5 mo old (89%). CONCLUSION: Clusters of parental, prenatal/pregnancy, infant,
      and toddler factors can be used to predict which children are at particularly
      high and low risk of becoming overweight kindergartners.

PMID- 23553170
TI  - Air space reduction tympanomastoidectomy repairs difficult perforations more
      reliably than tympanoplasty.
AB  - OBJECTIVES/HYPOTHESIS: Air space reduction tympanomastoidectomy improves outcomes
      over tympanoplasty in repairing tympanic membrane perforations in the presence of
      unfavorable risk factors. STUDY DESIGN: Retrospective review of 67 subjects' 87
      operations. METHODS: Interventions were tympanoplasty versus air space reduction
      tympanomastoidectomy. Risk factors were contracted mastoid air cells, previous
      failed operations, descent from the indigenous peoples of the Americas, and
      middle/ear mastoid volumes l<3 CC. Favorable outcomes were closure of the
      perforation, no decline in hearing, and creation of a self-cleaning mastoid bowl.
      RESULTS: Five out of 46 air space reduction tympanomastoidectomies failed to
      close their perforations (11%). Pure-tone threshold (PTA) worsened in 13/46 ears
      (28%). Four of 46 required mastoid bowl cleaning (9%). In contrast, 21 of 41
      tympanoplasties failed to close (51%). PTA worsened in 9/34 ears (26%). All four
      tympanoplasty failures treated with an air space reduction tympanomastoidectomy
      closed. Three of the seven tympanoplasty failures treated with a second
      tympanoplasty did not close. Statistical analysis found two risk factors more
      prevalent among the air space reduction tympanomastoidectomies: contracted
      mastoids (P = .019) and middle ear volumes <3 CC (P = .0001). Increased closure
      of perforations occurring after the air space reduction tympanomastoidectomy was
      also statistically significant (P = .0002). Descendants of indigenous peoples of
      the Americas trended toward better PTAs after their air space reduction
      tympanomastoidectomies than their tympanoplasties and showed statistically
      significant increases in closure of perforation (P = .0046). CONCLUSIONS: Air
      space reduction tympanomastoidectomy is an effective and safe method for closing
      tympanic membrane perforations.

PMID- 23553171
TI  - The term Hispanic/Latino: a note of caution.

PMID- 23553172
TI  - Assessment of cardiac autonomic functions by heart rate recovery, heart rate
      variability and QT dynamicity parameters in patients with acromegaly.
AB  - Cardiovascular complications are the most common causes of morbidity and
      mortality in acromegaly. However, there is little data regarding cardiac
      autonomic functions in these patients. Herein, we aimed to investigate several
      parameters of cardiac autonomic functions in patients with acromegaly compared to
      healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55%
      female, age:45.7 +/- 12.6 years) and 32 age- and gender-matched healthy subjects.
      All participants underwent 24 h Holter recording. Heart rate recovery (HRR)
      indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from
      maximal heart rate. All patients underwent heart rate variability (HRV) and QT
      dynamicity analysis. Baseline characteristics were similar except diabetes
      mellitus and hypertension among groups. Mean HRR1 (29.2 +/- 12.3 vs 42.6 +/- 6.5,
      p = 0.001), HRR2 (43.5 +/- 15.6 vs 61.1 +/- 10.8, p = 0.001) and HRR3 (46.4 +/-
      16.2 vs 65.8 +/- 9.8, p = 0.001) values were significantly higher in control
      group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p =
      0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square
      of successive differences in RR interval] (p = 0.001), PNN50 [proportion of
      differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency
      [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but
      low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in
      acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR
      slope (p = 0.01) were significantly higher in patients with acromegaly.
      Additionally, there were significant negative correlation of disease duration
      with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest
      that cardiac autonomic functions are impaired in patients with acromegaly.
      Further large scale studies are needed to exhibit the prognostic significance of
      impaired autonomic functions in patients with acromegaly.

PMID- 23553173
TI  - "Anatomy lesson of Frederik Ruysch" of 1670: a tribute to Ruysch's contributions
      to lymphatic anatomy.
AB  - BACKGROUND: Frederick Ruysch was one of the most prominent Dutch physicians of
      the seventeenth and eighteenth centuries. For more than 65 years, he was the
      Praelector Anatomiae (Lecturer of Anatomy) of the Amsterdam Guild of Surgeons.
      During his career, he conducted many dissections at the guild's theatre to teach
      anatomy. Ruysch was internationally renowned for his great dissection skills and
      his innovative techniques for preserving anatomical specimens. The "Anatomy
      Lesson of Dr. Frederik Ruysch" painted in 1670, is thought to be a group portrait
      undertaken to commemorate the officials of the Guild of Surgeons. Ruysch was
      portrayed performing an anatomical dissection of inguinal lymph nodes on the
      corpse of an executed criminal. This portrait is one of the earliest paintings
      focusing on the "lymphatic system." METHODS: We investigated the medical
      background of the painting by revisiting Ruysch's original work from the mid
      seventeenth century. His contributions to the early history of "lymphatic
      anatomy" are assessed and interpreted from the perspective of the renewed
      interest in "lymphatic imaging" today. RESULTS AND CONCLUSIONS: Frederik Ruysch
      should be considered one of the pioneers contributing to the early knowledge of
      the lymphatic system. He succeeded in dissecting the lymphatic vessels and valves
      with the aid of his innovative dissection and preservation techniques. The famous
      group portrait of the Amsterdam Guild of Surgeons with Ruysch demonstrating the
      lymph nodes pays tribute to his work on which we still rely today.

PMID- 23553176
TI  - Peduncular hallucinosis in a patient with subclavian steal syndrome: usefulness
      of Doppler ultrasonography.
AB  - The subclavian steal syndrome is characterized by retrograde flow within a
      vertebral artery ipsilateral to proximal subclavian artery high-grade stenosis or
      occlusion. It can cause vertebrobasilar insufficiency and hence diverse brainstem
      symptoms. Peduncular hallucinosis consists of visual images of brief duration
      that are related to thalamic or rostral brainstem lesions. We describe a patient
      with peduncular hallucinosis in the setting of subclavian steal syndrome.
      Inducing a hemodynamic challenge to the vertebrobasilar circulation elicited the
      patients visual symptoms. Thus, careful ultrasonographic evaluation with dynamic
      testing contributed to explain the physiopathology of the clinical symptoms.

PMID- 23553174
TI  - Extended lymphadenectomy in esophageal cancer is debatable.
AB  - Surgery is an essential part of the treatment of patients with esophageal
      carcinoma. However, there is no consensus on whether the surgical technique can
      be improved to promote better survival outcome. Specifically, the real value of
      the addition of a radical lymphadenectomy to the esophageal resection is still
      elusive and controversial. This paper focuses on the debate of esophagectomy and
      lymphadenectomy for the treatment of esophageal cancer. 

PMID- 23553177
TI  - Suction modulation for the laryngeal microdebrider.

PMID- 23553178
TI  - Dielectrophoresis 2013.

PMID- 23553184
TI  - [Work-Related Setting Approach with Health Counselling Supports a Healthy
      Lifestyle of Long-Term Unemployed Persons].
AB  - Unemployment is a major reason for health inequalties. In a pilot study (N=119),
      the acceptance and effectiveness of a low threshold health promotion intervention
      for older long-term unemployed persons were evaluated. Health counselling
      supported the participants in the development of a healthy lifestyle. 

PMID- 23553185
TI  - [Health Promotion for Long-Term Unemployed Persons].
AB  - A controlled trial to improve perceived health in a sample of long-term
      unemployed persons was conducted. As primary endpoint the SF12-questionnaire was
      used. The intervention was tailored to the specific needs of the long-term
      unemployed combining individual sessions based on motivational interviewing and
      group sessions designed with the participation of the participants. 365
      participants were enrolled in the study. 287 or, respectively, 148 unemployed
      persons participated at the 3-months/12-months follow-up assessments. A positive
      effect of the intervention in the setting of long-term unemployed persons has
      been shown for perceived health, mental health and changes towards more physical
      activity and healthier nutrition. 

PMID- 23553186
TI  - [Effect of Evidence-Based Risk Information on "Informed Choice" in Colorectal
      Cancer Screening: Randomised Controlled Trial].
AB  - Evidence-based information is a prerequisite for informed choice. We compared the
      effect of evidence-based information on colorectal cancer screening with standard
      information in a randomised controlled trial. The primary endpoint was informed
      choice. We randomised 1,577 people insured by a large German statutory health
      insurance scheme, the Gmunder Ersatzkasse (GEK). The evidence-based information
      significantly increased informed choices: 44.0% vs. 12.8%; (difference 31.2%, 99%
      CI 25.7-36.7%; P<0.001).

PMID- 23553187
TI  - [Evaluation of the "Obeldicks Light Training" Programme for Overweight Children
      and Adolescents].
AB  - In a randomised controlled study (n=34 intervention group, n = 32 control group)
      the effects of a 6-month outpatient training for overweight but not obese
      children and adolescents (BMI > 90(th) <= 97(th) percentile) were assessed up to
      12 months after the end of intervention. BMI-SDS reduction was the main outcome.
      The results show that the lifestyle intervention "Obeldicks light" is effective
      to reduce overweight, as well as blood pressure and several other risk parameters
      in overweight children. Effects are stable over a 12 months period.

PMID- 23553188
TI  - [Promoting Children from Socially Disadvantaged Backgrounds: The Mentoring
      Programme "Balu und Du"].
AB  - We aimed to determine whether socially disadvantaged elementary school children
      profit health-wise from their participation in the mentoring programme "Balu und
      Du". For the evaluation study we compared an intervention group of 141 children
      with a stratified control group of 158 children. The project was able to reach
      elementary school children from socially disadvantaged families. The treatment
      group showed distinct advancements in the areas of self-organisation, the ability
      to concentrate, as well as achievement and learning motivation. 

PMID- 23553189
TI  - [Health Promotion Training for Parents].
AB  - In this research project, we have analysed how parent education programmes can be
      integrated into the settings kindergarten, school and community family services.
      Using the example of 3 well-established prevention programmes for mothers and
      fathers we were able to identify the conditions for an improved usage of the
      facilities offered by the programme. We found evidence that the embedding of the
      programmes in such settings made it possible to approach mothers and fathers from
      disadvantaged social backgrounds to a higher degree than with traditional
      approaches. 

PMID- 23553190
TI  - [Costs of illness for asthma and COPD in adults in Germany].
AB  - BACKGROUND; Asthma and COPD have a high and growing epidemiological impact
      worldwide, and it is often indicated that significant economic costs are linked
      to this. The aim of this review is to estimate the cost-of-illness for both
      diseases for adults in Germany. METHODS: A systematic search of Pubmed, Embase,
      EconLit and Business Source Complete was performed for the years 1995-2012 to
      identify German cost-of-illness studies for asthma and COPD in German or English
      language. 6 studies for asthma, 7 studies for COPD and 1 for both diseases met
      the inclusion criteria. The results of the identified studies were extrapolated
      to 2010 prices and compared within the same disease. RESULTS: In spite of the
      heterogeneity in methodology and results, medication was identified as the most
      important component of direct costs and work loss as the most important component
      of indirect costs. All in all, the estimated costs per case of illness and year
      for asthma sum up to 445 to 2 543 ? and for COPD to 1 212 to 3 492 ?. CONCLUSION:
      The analysed cost-of-illness studies confirm that asthma and COPD are costly but
      results vary markedly. COPD due to its higher costs per case and its similar
      prevalence causes higher macroeconomic costs. Our results emphasise the economic
      relevance of prevention and disease management for these lung diseases.

PMID- 23553191
TI  - Outcome predictors in squamous cell carcinoma of the maxillary alveolus and hard
      palate.
AB  - OBJECTIVES/HYPOTHESIS: Hard palate and maxillary alveolus are two commonly
      grouped oral cavity subsites due to their anatomic contiguity and oncologic
      disease behavior. Few studies have been conducted investigating clinical
      presentation, staging, prevalence of cervical metastases, and outcomes in this
      population. The primary objective of this study was to analyze predictors of
      disease-free survival (DFS) in surgically treated patients, particularly as it
      relates to the role of neck dissection. STUDY DESIGN: Cohort study with planned
      data collection. METHODS: This cohort study used planned data collection over 15
      years (1994-2008) at a large tertiary care cancer center to study all patients
      presenting with squamous cell carcinoma of the maxillary alveolus and hard palate
      treated surgically. Univariate and multivariate Cox regression analyses were used
      to identify predictors of DFS. RESULTS: Ninety-seven patients met the inclusion
      criteria (54 male, 56%). The majority of patients (54, 56%) presented with
      locally advanced disease (cT3, cT4). Occult nodal metastases were noted in 26%
      (17 of 65) of patients clinically staged as N0. The 3-year DFS was 70% (95%
      confidence interval = 59%-78%) with a median time to failure of 1.1 years (range
      = 0.3-9.7 years). Cox regression multivariate model demonstrated that advanced
      pathologic T stage, hard palate tumor site, and poorly differentiated tumor grade
      were each independent predictors of DFS. CONCLUSIONS: A significant portion of
      the patients with hard palate and maxillary alveolus tumors harbor occult
      cervical metastases. Elective neck dissection in the high-risk patients may
      potentially be beneficial in providing more accurate staging and improving DFS.
      LEVEL OF EVIDENCE: 2b.

PMID- 23553192
TI  - Soluble receptor for advanced glycation end products alleviates nephritis in
      (NZB/NZW)F1 mice.
AB  - OBJECTIVE: To investigate the efficacy of different doses of the soluble form of
      the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc
      portion of immunoglobulin) in the treatment of nephritis in lupus-prone mice, in
      comparison with the efficacy of combination therapy with mycophenolate mofetil
      plus prednisolone. METHODS: Twenty-eight female (NZB/NZW)F1 mice were divided
      into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 MUg], or
      mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were
      evaluated. Immune complex deposition and the nuclear translocation of NF-kappaB
      in the kidney tissue were assessed by immunofluorescence staining. Serum
      concentrations of anti-double-stranded DNA (anti-dsDNA) and IgG subclasses were
      also measured. The population of T cells was evaluated using a fluorescence
      activated cell sorter, and expression of intracellular adhesion molecule 1 and
      vascular cell adhesion molecule 1 in the kidney tissue was assessed by
      immunohistochemical staining. RESULTS: In comparison with untreated mice, mice
      treated with 1 or 2 MUg sRAGE showed significantly reduced proteinuria and
      attenuated histologic renal damage, with efficacy comparable to that of
      combination therapy. Treatment with 2 MUg sRAGE significantly reduced immune
      complex deposition and decreased the serum concentrations of anti-dsDNA, IgG2a,
      IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF
      kappaB in the kidney, resulting in reduction in the expression of downstream
      genes of NF-kappaB in vivo and in vitro. Furthermore, sRAGE effectively modified
      T cell populations. CONCLUSION: Treatment with sRAGE significantly improved
      nephritis in lupus-prone mice, with efficacy comparable to that of standard
      induction treatment for lupus nephritis. These data suggest that sRAGE has
      antiinflammatory effects on the pathophysiology of lupus nephritis and could
      serve as a potent new therapy for this disease.

PMID- 23553193
TI  - From the new Editor-in-Chief: a sense of personal identity with the Journal of
      Plant Research.

PMID- 23553194
TI  - Oral contraceptive use and uterine leiomyoma risk: a meta-analysis based on
      cohort and case-control studies.
AB  - PURPOSE: To review the epidemiological and clinical evidence for the association
      between oral contraceptives (OCs) and uterine leiomyoma (UL). METHODS: Several
      databases (Pubmed, Cochrane Central, OVID, SpringerLink, Clinical Evidence, and
      Google scholar) and reference lists were searched through March 2012 with no
      restrictions. INCLUSION CRITERIA: cohort or case-control studies; the exposure of
      interest was OCs; the outcome of interest was UL; relative risk (RR) or odds
      ratio (OR) (or data to calculate them) were reported. Two independent reviewers
      assessed eligibility criteria and extracted data. RESULTS: Eleven literatures
      involving 8,990 UL patients and 1,31,055 participants were included from 3,017
      studies initially found. The influence of OCs on UL risk was assessed by
      comparing "ever", "current" or "former" users and "never" users. Meta-analysis
      indicated that OCs use did not increase UL morbidity ("ever" vs "never": risk
      ratio [RR] 0.88; 95 % confidence interval [95 % CI] 0.75-1.04. "current" vs
      "never": RR 0.43; 95 % CI 0.25-0.73. "former" vs "never": RR 0.96; 95 % CI 0.84
      1.08). Dose-response analysis showed the risk of UL morbidity was reduced by 17 %
      in "ever" users for 5 years or more (P trend = 0.006). However, the results have
      to be viewed with caution because there was significant heterogeneity (I (2):
      from 64 to 92 %). CONCLUSIONS: Although the role of potential bias and evidence
      of heterogeneity should be carefully evaluated, the present study suggests that
      UL should not be considered a contra-indication for OCs use.

PMID- 23553195
TI  - Comparison of "sandwich chemo-radiotherapy" and six cycles of chemotherapy
      followed by adjuvant radiotherapy in patients with stage IIIC endometrial cancer:
      a single center experience.
AB  - OBJECTIVE: To compare "sandwich chemo-radiotherapy" with six cycles of
      chemotherapy followed by adjuvant radiotherapy with respect to tolerability and
      acute toxicity. MATERIALS AND METHODS: Twenty-five women with surgically staged
      IIIC endometrial cancer were included. Treatment consisted of either three cycles
      of paclitaxel (175 mg/m2) and carboplatin (AUC 6) on a q21-day schedule followed
      by irradiation (45-50.4 Gy) or six cycles of the same chemotherapy followed by
      radiotherapy. Acute toxicity related to either chemotherapy or radiotherapy was
      evaluated. RESULTS: Median age was 61.5 years (range 36-83 years). Eleven
      patients had sandwich chemo-radiotherapy, and the other 14 patients had 6 cycles
      of chemotherapy followed by radiotherapy. Three out of the five patients who
      could not complete all the cycles in the sandwich chemo-radiotherapy group had
      pelvic and para-aortic radiotherapy. Acute radiotherapy related grade 1-2
      gastrointestinal system (GIS) and genitourinary system (GUS) toxicities were
      observed in 72.8 and 63.6 % of patients, respectively, for sandwich group.
      Undesired treatment breaks in the course of radiotherapy were observed in six
      patients for sandwich chemo-radiotherapy and in one patient receiving six cycles
      of chemotherapy followed by radiotherapy. All the patients who had undesired
      treatment breaks in the sandwich chemo-radiotherapy group had pelvic and para
      aortic radiotherapy. CONCLUSION: Sandwich chemo-radiotherapy seems to be more
      toxic particularly for patients who had pelvic and para-aortic irradiation.
      Therefore, it might be more convenient to delay radiotherapy after six cycles of
      chemotherapy for patients with the indication of pelvic para-aortic radiotherapy.

PMID- 23553196
TI  - The expression of BRCA1, P53, KAI1, and Nm23 in ovaries of BRCA1 mutation
      carriers after prophylactic adnexectomy.
AB  - INTRODUCTION: High mortality rate, absence of reliable methods for early
      diagnosis and poor prognosis of advanced ovarian cancer prompted to investigate
      the role of prophylactic oophorectomy in BRCA1 mutation carriers as well as
      evaluate the expression of BRCA1, p53, Nm23, and KAI1 proteins in ovarian tissue
      from these patients. MATERIALS AND METHODS: Ovaries from BRCA1 mutation carriers
      underwent prophylactic adnexectomy and control group of patients were operated
      from other than cancer reasons. The expression of selected proteins was studied
      using immunohistochemical staining. The intensity of immunostaining and the
      number of tumor cells showing the reaction for selected proteins were analyzed.
      RESULTS: We have analyzed ovarian tissues from 18 BRCA1 mutation carriers and 11
      women included in control group. Positive expression of BRCA1 protein was
      presented in 83.3 % cases in BRCA1 mutation carriers and in 72.7 % in the control
      group (p > 0.05). Positive expression of p53 protein was observed, respectively,
      in 27.8 vs. 36.4 % (p > 0.05), Nm23 protein 77.7 vs. 90.9 % (p > 0.05), and KAI1
      in 72.2 vs. 72.7 % (p > 0.05). Mean percent of tumor cells that showed the
      reaction for selected proteins as well as the intensity of immunostaining for all
      analyzed proteins seems to be lower in BRCA1 mutation carriers. CONCLUSIONS:
      However, any significant differences between study group and control group have
      not been found; there were similar trends showing reduced expression of studied
      proteins in BRCA1 mutation carriers.

PMID- 23553197
TI  - Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of
      endometriosis.
AB  - PURPOSE: To determine, with extended receiver operating characteristic (ROC)
      curve analysis, the diagnostic value of cytokines showing significantly different
      peritoneal concentrations between women with and without endometriosis. METHODS:
      Multiplex cytokine concentration measurement of IL-2, IL-4, IL-6, IL-10, TNF
      alpha and IFN-gamma levels in peritoneal fluid of women with minimal to mild (n =
      10) and moderate to severe (n = 26) endometriosis, and 42 controls. RESULTS: Only
      IL-6 and IL-10 concentrations were significantly higher in endometriosis patients
      than in controls. Specifically, significantly higher IL-6 and IL-10 levels were
      found in moderate to severe but not in minimal to mild endometriosis as compared
      to controls. For evaluation of diagnostic significance, ROC analysis determined
      discriminating parameters for IL-6, while those calculated for IL-10 were
      useless. Importantly, ROC analysis for IL-6 levels limited to women with moderate
      to severe endometriosis showed the highest area under the curve with the sample
      size sufficient to achieve 90 % power of the test. Finally, extended ROC
      including cost of analysis for this group of patients determined the optimal cut
      off leading to high specificity and positive likelihood ratio resulting in 79 %
      effectiveness of the test. CONCLUSIONS: While our outcomes show moderate
      usefulness of peritoneal IL-6 levels in discrimination of moderate to severe
      endometriosis, further studies might be needed to determine the usefulness of
      peritoneal IL-6 levels in detection of early stages of endometriosis, as such a
      finding would be more relevant in clinical decision making.

PMID- 23553198
TI  - The FCRL3 -169T>C polymorphism and the risk of endometriosis-related infertility
      in a Polish population.
AB  - OBJECTIVE: Recently, the FCRL3 -169T>C (rs7528684) single-nucleotide polymorphism
      (SNP) has been demonstrated to be a risk factor of endometriosis related
      infertility. We studied whether the FCRL -169T>C SNP can be associated with
      endometriosis-related infertility in a sample of the Polish population METHODS:
      Using PCR-RFLP analysis we genotyped 141 infertile women with endometriosis and
      519 fertile women. FCRL3 transcript levels were determined by reverse
      transcription and real-time quantitative PCR analysis in CD19(+) B cells from
      women with endometriosis-associated infertility and fertile women RESULTS: We
      found a significantly increased frequency of the FCRL3 C/C genotype in women with
      endometriosis-associated infertility than controls [OR = 1.681 (95 % CI = 1.120
      2.522, p = 0.0116, p corr = 0.0348)]. There was also a statistically increased
      frequency of the C/C and C/T genotypes in patients compared with controls [OR =
      2.009 (95 % CI = 1.214-3.324, p = 0.0059, p corr = 0.0177)]. The p value of the
      chi (2) test for the trend observed for the FCRL3 -169T>C polymorphism was also
      statistically significant (p trend = 0.0012, p corr = 0.0036). We also found
      significantly increased FCRL3 transcript levels in carriers of the FCRL3 -169 CC
      vs TT and CT vs TT genotype both in women with endometriosis-related infertility
      (p = 0.012; p = 0.015) and fertile women (p = 0.017; p = 0.032) CONCLUSIONS:
      FCRL3 -169T>C polymorphism alters the expression of FCRL3 and can be a risk
      factor of endometriosis-related infertility.

PMID- 23553199
TI  - The association of RANK gene C421T and C575T polymorphisms with bone mineral
      density in postmenopausal Turkish women.
AB  - PURPOSE: To investigate the association between C421T polymorphism within exon 4,
      C575T polymorphism within exon 6 of the RANK gene and bone mineral density (BMD)
      variations in postmenopausal Turkish women. METHODS: One hundred seventy-eight
      postmenopausal women (patients = 100 and controls = 78) who applied to Ege
      University Faculty of Medicine, Department of Physical Medicine and
      Rehabilitation, for osteoporosis examination were analyzed. BMDs of the lumbar
      spine and femoral sites were measured. Patient and control groups were
      established based on their T-score values being above and/or below -1. After
      venous blood sampling, C421T and C575T polymorphisms of the RANK gene were
      assessed through PCR process following DNA extraction. RESULTS: Genotype
      frequencies for the C421T and C575T polymorphisms were compared between the
      control group and the patient group. No significant difference was detected
      between the two groups for both polymorphisms. There was also no significant
      difference between the control and patient groups in terms of the combined
      genotype (p = 0.752) and the combined haplotype analysis of the C421T and C575T
      polymorphisms (p = 0.723). In the control and patient groups separately, no
      significant differences in BMD values either at the femoral sites or at the
      lumbar spine were detected between the combined genotypes of the two
      polymorphisms. CONCLUSIONS: The genotypes, combined genotypes and allele
      frequencies of C421T and C575T polymorphisms of the RANK gene have not been found
      to be associated with BMD in Turkish women. Further studies including both sexes
      and more cases are required.

PMID- 23553200
TI  - Anti-Mullerian hormone and insulin resistance in classic phenotype lean PCOS.
AB  - PURPOSE: This study is designed to explore the correlation between AMH levels and
      IR in normal weight PCOS women. MATERIALS AND METHODS: This prospective study was
      conducted on 55 patients, who were admitted to obstetrics and gynecology
      department of a university clinic. Study group was consisted of 34 patients
      diagnosed as polycystic ovary syndrome (PCOS) according to the Rotterdam
      Criteria, whereas control group was consisted of 21 healthy volunteers without
      any features of clinical or biochemical hyperandrogenism, who had regular
      menstrual cycles. BMI >= 25 kg/m(2) were considered overweight and obese and
      excluded. Blood samples were obtained during days 2-3 after spontaneous menses or
      progesterone-induced withdrawal bleeding after overnight fasting for at least 12
      h. The weight, height, hip and waist circumferences of the patients were
      measured. Fasting insulin and glucose (FPG) levels were used for calculating
      different insulin resistance indexes (Homeostatic Model Assessment (HOMA-IR),
      Quantitative Insulin Sensitivity Check Index (QUICKI)). RESULTS: No significant
      difference was found between PCOS and control groups regarding the mean age, BMI,
      waist to hip ratio (WHR), mean values of FPG, FPG/insulin ratio and HOMA B (p >
      0.05). AMH values were significantly higher in PCOS cases when compared with
      controls (4.7 vs. 3.4 ng/mL) (p < 0.05).The mean values of HOMA-IR and QUICKI
      indexes were significantly higher among PCOS cases when compared with controls.
      E2 levels were significantly lower and Total-T were significantly higher in PCOS
      patients. When PCOS cases are categorized according to the existence of IR, no
      difference in Total-T and AMH levels between both groups. Although not
      statistically significant, a negative correlation of AMH with HOMA-IR and a
      positive correlation with QUICKI index were found. Among the hormone parameters,
      AMH was found to be positively correlated with Total-T (r = 0.332, p = 0.013).
      CONCLUSION: Although the relation between AMH and androgen production is
      supported by current evidence, the mechanism underlying the relation between AMH
      and insulin resistance is not clear yet.

PMID- 23553201
TI  - Effects of gender roles, child wish motives, subjective well-being, and marital
      adjustment on infertility-related stress: a preliminary study with a Hungarian
      sample of involuntary childless men and women.
AB  - PURPOSE: The aim of the study is to investigate the infertility-related stress in
      a Hungarian infertile population and examine the effects of gender roles, child
      wish motives, subjective well-being, and marital relationship on the experience
      of infertility according to our self-constructed conceptual framework. METHODS:
      Validated self-report questionnaires measuring the factors of the conceptual
      framework were taken in the study carried out in a sample of 53 people attending
      the fertility unit of a Hungarian clinic. RESULTS: Infertility-related global
      stress, infertility-related social concerns, and general health problems have
      more intensive effect on women than on men (all p < 0.05). Women from the
      infertile group scored higher their femininity (p < 0.001) and lower their
      general health (p < 0.05) than the reference population. Infertile men believe
      deeper in meaning of life than women (p < 0.05) or reference population (p <
      0.01). Femininity (beta = 0.460, p < 0.05), traditional gender role concepts
      (beta = -0.248, p < 0.05), general health (beta = -0.474, p < 0.05), and marital
      relationship (beta = -0.251, p < 0.05) play the strongest role to predict stress
      caused by infertility. CONCLUSIONS: The current study emphasizes the importance
      of interrelations of gender role attitudes, gender role identification, general
      health, and satisfaction in couple relationship with infertility-related stress.
      In further investigations, both social and personal aspects and their effect on
      experiencing infertility need to be measured in infertile people, particularly in
      different cultural settings.

PMID- 23553202
TI  - Genitourinary infection prevalence among women who used an intrauterine device or
      oral contraceptives.
AB  - PURPOSE: The study aimed at investigating genitourinary infection prevalence
      among women who used an intrauterine device (IUD) and oral contraceptives (OC) in
      relation with their socio-demographic characteristics. METHODS: The study was
      conducted at the Mother and Child Health and Family Planning center between
      October 2011 and February 2012 and included 81 women who used IUD, 84 who used
      OC, and 84 who did not use artificial contraceptive methods (coitus interruptus).
      RESULTS: It was found that there was a difference between the three groups in
      terms of urinary system infection (X (2) = 9.85, p = 0.000) and genital infection
      (X (2) = 8.29, p = 0.001). It was also observed that urinary infection was more
      common in the OC group, whereas genital infection was more common in the IUD
      group. In urinary culture, it was seen that Enterobacter species was the most
      common microorganism among the group who used an IUD, while Escherichia coli was
      the most common microorganism in the group who used OC and the control. In
      vaginal cultures, Candida albicans was determined to be the first isolated
      microorganism among the group who used OC, IUD, and the control. CONCLUSION: It
      is believed that the most significant reason for genitourinary infections among
      women was inadequate hygiene practices rather than use of different contraception
      methods.

PMID- 23553204
TI  - [Galli-Galli disease. Review of the literature].

PMID- 23553203
TI  - Support for the N-methyl-D-aspartate receptor hypofunction hypothesis of
      schizophrenia from exome sequencing in multiplex families.
AB  - IMPORTANCE: Schizophrenia is a complex genetic disorder demonstrating
      considerable heritability. Genetic studies have implicated many different genes
      and pathways, but much of the genetic liability remains unaccounted for.
      Investigation of genetic forms of schizophrenia will lead to a better
      understanding of the underlying molecular pathways, which will then enable
      targeted approaches for disease prevention and treatment. OBJECTIVE: To identify
      new genetic factors strongly predisposing to schizophrenia in families with
      multiple affected individuals with schizophrenia. DESIGN: We performed genome
      wide array comparative genomic hybridization, linkage analysis, and exome
      sequencing in multiplex families with schizophrenia. SETTING: Probands and their
      family members were recruited from academic medical centers. PARTICIPANTS: We
      intended to identify rare disease-causing mutations in 5 large families where
      schizophrenia transmission appears consistent with single-gene inheritance.
      INTERVENTION: Array comparative genomic hybridization was used to identify copy
      number variants, while exome sequencing was used to identify variants shared in
      all affected individuals and linkage analysis was used to further filter shared
      variants of interest. Analysis of select variants was performed in cultured cells
      to assess their functional consequences. MAIN OUTCOME MEASURES: Rare inherited
      disease-related genetic mutations. RESULTS: No segregating rare copy number
      variants were detected by array comparative genomic hybridization. However, in
      all 5 families, exome sequencing detected rare protein-altering variants in 1 of
      3 genes associated with the N -methyl-D-aspartate (NMDA) receptor. One pedigree
      shared a missense and frameshift substitution of GRM5, encoding the metabotropic
      glutamate receptor subtype 5 (mGluR5), which is coupled to the NMDA receptor and
      potentiates its signaling; the frameshift disrupts binding to the scaffolding
      protein tamalin and increases mGluR5 internalization. Another pedigree
      transmitted a missense substitution in PPEF2, encoding a calmodulin-binding
      protein phosphatase, which we show influences mGluR5 levels. Three pedigrees
      demonstrated different missense substitutions within LRP1B, encoding a low
      density lipoprotein receptor-related protein tied to both the NMDA receptor and
      located in a chromosome 2q22 region previously strongly linked to schizophrenia.
      CONCLUSIONS AND RELEVANCE: Exome sequencing of multiplex pedigrees uncovers new
      genes associated with risk for developing schizophrenia and suggests potential
      novel therapeutic targets.

PMID- 23553205
TI  - Image of the month. Esophageal injury.

PMID- 23553207
TI  - Associated social factors of thyroid disorders in adults and the very old in the
      UK.

PMID- 23553206
TI  - Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients
      treated with chemotherapy.
AB  - Survival of bladder cancer patients depends on several factors including disease
      stage and grade at diagnosis, age, health status of the patient and the applied
      treatment. Several studies investigated the role of DNA repair genetic variants
      in cancer susceptibility, but only few studies investigated their role in
      survival and response to chemotherapy for bladder cancer. We genotyped 28 single
      nucleotide polymorphisms (SNP) in DNA repair genes in 456 bladder cancer
      patients, reconstructed haplotypes and calculated a score for combinations of the
      SNPs. We estimated Hazard Ratios (adjHR) for time to death. Among patients
      treated with chemotherapy, variant alleles of five SNPs in the XRCC1 gene
      conferred better survival (rs915927 adjHR 0.55 (95%CI 0.32-0.94); rs76507 adjHR
      0.48 (95%CI 0.27-0.84); rs2854501 adjHR 0.25 (95%CI 0.12-0.52); rs2854509 adjHR
      0.21 (95%CI 0.09-0.46); rs3213255 adjHR 0.46 (95%CI 0.26-0.80). In this group of
      patients, an increasing number of variant alleles in a XRCC1 gene score were
      associated with a better survival (26% decrease of risk of death for each
      additional variant allele in XRCC1). By functional analyses we demonstrated that
      the previous XRCC1 SNPs confer lower DNA repair capacity. This may support the
      hypothesis that survival in these patients may be modulated by the different DNA
      repair capacity determined by genetic variants. Chemotherapy treated cancer
      patients bearing an increasing number of "risky" alleles in XRCC1 gene had a
      better survival, suggesting that a proficient DNA repair may result in resistance
      to therapy and shorter survival. This finding may have clinical implications for
      the choice of therapy. 

PMID- 23553208
TI  - Improving management and patient care in lentigo maligna by mapping with in vivo
      confocal microscopy.
AB  - IMPORTANCE: Lentigo maligna (LM) is a clinical, pathologic, and therapeutic
      challenge with a higher risk of local recurrence than other types of melanoma
      correctly treated and also carries the cosmetically sensitive localization of
      head and neck. OBJECTIVE: To determine whether in vivo reflectance confocal
      microscopy (RCM) mapping of difficult LM cases might alter patient care and
      management. DESIGN: Analysis of LM and LM melanoma (LMM) in a series of patients
      with large facial lesions requiring complex reconstructive surgery and/or
      recurrent or poorly delineated lesions at any body sites were investigated.
      SETTINGS: Two tertiary referral melanoma centers in Sydney, Australia.
      PARTICIPANTS: Thirty-seven patients with LM (including 5 with LMM) were mapped
      with RCM. Fifteen patients had a recurrent LM, including 9 with multiple prior
      recurrences. The LM was classified amelanotic in 10 patients, lightly pigmented
      in 9, and partially pigmented in 18. INTERVENTIONS: The RCM images were obtained
      in 4 radial directions (allowing for anatomic barriers) for LM margin delineation
      using an RCM LM score previously described by our research team. MAIN OUTCOME
      MEASURES: Differences in the margin of LM as determined by RCM vs dermoscopy vs
      histopathologic analysis. RESULTS: Seventeen of 29 patients (59%) with
      dermoscopically visible lesions had subclinical (RCM-identified) disease evident
      more than 5 mm beyond the dermoscopy margin (ie, beyond the excision margin
      recommended in published guidelines). The RCM mapping changed the management in
      27 patients (73%): 11 patients had a major change in their surgical procedure,
      and 16 were offered radiotherapy or imiquimod treatment as a consequence of the
      RCM findings. Treatment was surgical in 17 of 37 patients. Surgical excision
      margins (based on the RCM mapping) were histopathologically involved in only 2
      patients, each of whom had an LM lesion larger than 6 cm. CONCLUSIONS AND
      RELEVANCE: In vivo RCM can provide valuable information facilitating optimal
      patient care management.

PMID- 23553209
TI  - Sleep characteristics and cardiovascular events in a large Swedish cohort.
AB  - Limited evidence suggests that the association between sleep duration and
      cardiovascular events is strongest in individuals who also report sleep
      disturbances. We investigated sleep duration and insomnia symptoms in relation to
      incident cardiovascular events in the Swedish National March Cohort comprising
      41,192 adults. Habitual sleep duration and difficulty falling asleep, difficulty
      maintaining sleep, early morning awakening, and nonrestorative sleep were self
      reported in 1997. During 13.2 years of follow-up, we identified 4,031 events
      (myocardial infarction, stroke, heart failure, or death from cardiovascular
      disease) in the Swedish National Patient Register and the Cause of Death
      Register. After adjustment for potential confounders, short sleep duration (<=5
      h) was associated with slightly increased risks of overall cardiovascular events
      and, specifically, myocardial infarction: hazard ratio, HR (95% confidence
      interval) 1.24 (1.06-1.44) and 1.42 (1.15-1.76), respectively. These HRs were
      attenuated as we included BMI, depressive symptoms and other relevant covariates
      in our analysis. Insomnia symptoms per se were unrelated to risk. However, in a
      joint analysis, there was some evidence that short sleepers who reported frequent
      insomnia symptoms had the highest HRs (1.26-1.39) of overall cardiovascular
      events. Short sleep or insomnia symptoms without the other conferred no increased
      risk. Our results suggest that symptoms of sleep disturbance should be taken into
      account when assessing the association between short sleep and cardiovascular
      disease.

PMID- 23553211
TI  - Usefulness of multi-channels in intraoperative spinal cord monitoring: multi
      center study by the Monitoring Committee of the Japanese Society for Spine
      Surgery and Related Research.
AB  - OBJECT: The purpose of this study is to analyze the data in terms of the number
      of channels employed to examine the usefulness of multi-channels in
      intraoperative spinal cord monitoring. METHODS: The prerequisites for inclusion
      in the baseline data were as follows: (1) cases in which only CMAP monitoring was
      conducted; (2) cases in which monitoring was conducted under the same stimulation
      condition and the recording condition. Cases where inhalation anesthesia was used
      or muscle relaxants were used as maintenance anesthesia was excluded from the
      baseline data. Of the 6,887 cases, 884 cases met the criteria. The items examined
      for each of the different numbers of channels were the sensitivity and
      specificity, the false positive rate, the false negative rate, and the coverage
      rate of postoperative motor deficit muscles. RESULT: To examine these two items
      in terms of the number of channels, the 4-channel group had lower sensitivity and
      specificity scores compared with the 8- and 16-channel groups (4 channels 73/93
      %, 8 channels 100/97 %, 16 channels 100/95 %). Only four channels were derived
      for these cases and the coverage of postoperative motor deficit muscles was 38 %
      with only 30 out of the 80 postoperative motor deficit muscles in total being
      monitored. In the 8-channel group, it was 60 % with 12 of the 20 postoperative
      motor deficit muscles being monitored. The 16-channel group had 100 % coverage
      rate of postoperative motor deficit muscles. CONCLUSION: We suggest that multi
      channel monitoring of at least eight channels is desirable for intraoperative
      spinal cord monitoring.

PMID- 23553212
TI  - The unfolded protein response triggered by environmental factors.
AB  - Endoplasmic reticulum (ER) stress and consequent unfolded protein response (UPR)
      are involved in a diverse range of pathologies including ischemic diseases,
      neurodegenerative disorders, and metabolic diseases, such as diabetes mellitus.
      The UPR is also triggered by various environmental factors; e.g., pollutants,
      infectious pathogens, therapeutic drugs, alcohol, physical stress, and
      malnutrition. This review summarizes current knowledge on environmental factors
      that induce ER stress and describes how the UPR is linked to particular
      pathological states after exposure to environmental triggers.

PMID- 23553213
TI  - The UPR in atherosclerosis.
AB  - Multiple systemic factors and local stressors in the arterial wall can disturb
      the functions of endoplasmic reticulum (ER), causing ER stress in endothelial
      cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation
      and progression of atherosclerosis. As a protective response to restore ER
      homeostasis, the unfolded protein response (UPR) is initiated by three major ER
      sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein
      1alpha (IRE1alpha), and activating transcription factor 6 (ATF6). The activation
      of the various UPR signaling pathways displays a temporal pattern of activation
      at different stages of the disease. The ATF6 and IRE1alpha pathways that promote
      the expression of protein chaperones in ER are activated in ECs in athero
      susceptible regions of pre-lesional arteries and before the appearance of foam
      cells. The PERK pathway that reduces ER protein client load by blocking protein
      translation is activated in SMCs and macrophages in early lesions. The activation
      of these UPR signaling pathways aims to cope with the ER stress and plays a pro
      survival role in the early stage of atherosclerosis. However, with the
      progression of atherosclerosis, the extended duration and increased intensity of
      ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this
      circumstance, the PERK pathway induces expression of death effectors, and
      possibly IRE1alpha activates apoptosis signaling pathways, leading to apoptosis
      of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death
      is associated with plaque instability and the clinical progression of
      atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly
      to macrophage differentiation in lesions. Therapeutic approaches targeting the
      UPR may have promise in the prevention and/or regression of atherosclerosis.
      However, more progress is needed to fully understand all of the roles of the UPR
      in atherosclerosis and to harness this information for therapeutic advances.

PMID- 23553215
TI  - Low-density granulocytes: a distinct class of neutrophils in systemic
      autoimmunity.
AB  - Recent studies have renewed the interest on the potential role that neutrophils
      play in the development of systemic lupus erythematosus (SLE) and other
      autoimmune conditions. A distinct subset of proinflammatory, low-density
      granulocytes (LDGs) isolated from the peripheral blood mononuclear cell fractions
      of patients with SLE has been described. While the origin and role of LDGs needs
      to be fully characterized, there is evidence that these cells may contribute to
      lupus pathogenesis and to the development of end-organ damage through heightened
      proinflammatory responses, altered phagocytic capacity, enhanced ability to
      synthesize type I interferons, and to kill endothelial cells. Furthermore, these
      cells readily form neutrophil extracellular traps, a phenomenon that may promote
      autoantigen externalization and organ damage. This review examines the biology
      and potential origin of LDGs, describes the ultrastructural characteristics of
      these cells, and discusses their putative pathogenic role in systemic autoimmune
      diseases.

PMID- 23553219
TI  - Palliative surgery for head and neck cancer with extensive skin involvement.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the role of regional and free tissue transfer
      for the palliative management of head and neck cancer with extensive skin
      involvement. STUDY DESIGN: Case Series. METHODS: A retrospective review was
      performed of patients treated for head and neck cancer with involvement of the
      skin at the Mount Sinai Medical Center over a 5-year period (2006-2010). Only
      patients with extensive skin involvement and unresectable tumors who underwent
      palliative resection and reconstruction were included in the review. Subjects
      were analyzed for age, gender, performance status, primary site, tumor histology,
      extent of invasion, type of reconstruction, hospital course, wound complications,
      adjuvant therapy, survival, and cause of death. RESULTS: Twenty-five patients met
      the inclusion criteria for the review. Fourteen patients (56%) underwent regional
      flap reconstruction, and 11 patients (44%) underwent free flap reconstruction.
      The average length of stay was 7 days. Twenty-four patients (96%) had a medically
      uncomplicated postoperative hospital course. Nineteen patients (76%) were treated
      with adjuvant palliative radiotherapy and/or chemotherapy. Long-term follow-up
      was achieved for 19 patients. The median follow up in this group was 9.5 months.
      Eleven of the 21 patients (52%) developed wound complications postoperatively.
      Eight of these were minor wound dehiscences, while three developed major wound
      complications. Four patients (16%) had distant metastasis at the time of surgery,
      and the median time to develop distant metastases after surgery was 6 months.
      Median survival time was 9.5 months. Twenty-two patients (88%) were discharged in
      the care of their families with appropriate pain management and without the need
      for extensive wound care. CONCLUSIONS: For unresectable tumors with extensive
      skin involvement, palliative resection and reconstruction is a reasonable
      treatment option. Although survival may not be affected, addressing the odor,
      bleeding, pain, and infection associated with skin involvement has the potential
      to improve a patient's quality of life. LEVEL OF EVIDENCE: 4.

PMID- 23553216
TI  - Heme oxygenase inhibition increases blood pressure in pregnant rats.
AB  - BACKGROUND: During normal gestation, the placenta is a relatively hypoxic organ
      and, as such, is subject to significant oxidative stress. In the preeclamptic
      patient, inadequate remodeling of the maternal vasculature severely exacerbates
      placental oxidative stress, which has been shown to be an important component of
      maternal hypertension. There is emerging evidence that Heme Oxygenase-1 (HO-1)
      acts as an important regulator of placental and cardiovascular function during
      normal pregnancy. Here, we have examined the effect of Heme Oxygenase (HO)
      inhibition in late gestation on maternal blood pressure, angiogenic balance, and
      placental oxidative stress in pregnant rats. METHODS: HO activity was inhibited
      with tin mesoporphyrin (SnMP), which was administered on gestational day 14, and
      blood pressure was measured on gestational day 19. Placental angiogenic balance
      and plasma Vascular Endothelial Growth Factor (VEGF) were determined by sandwich
      enzyme-linked immunosorbent assay. Nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase activity was measured by lucigenin chemilluminescence. RESULTS:
      In response to SnMP treatment, maternal mean arterial pressure (MAP) was
      significantly increased (99+/-1 vs. 113+/-2mm Hg; P < 0.05; n = 15 per group).
      Placental soluble fms-like tyrosine kinase-1 (sFlt-1) (631+/-47 vs. 648+/-26
      pg/mg; P = 0.76) levels in the placenta were not affected by HO inhibition.
      Additionally, there was no significant difference in free VEGF in the maternal
      circulation (287+/-22 vs. 329+/-14 pg/ml; P = 0.11). There was, however, a
      significant decrease in placental VEGF (23+/-2 vs. 16+/-1 pg/mg; P < 0.05) and a
      significant increase in placental NADPH oxidase activity in SnMP-treated rats
      (2021+/-238 vs. 3005+/-301 RLU/min/mg; P < 0.05). CONCLUSIONS: Our results
      demonstrate that HO is an important regulator of blood pressure and an important
      antioxidant in the developing placenta.

PMID- 23553214
TI  - Neutrophils in innate and adaptive immunity.
AB  - Neutrophils have long been viewed as short-lived cells crucial for the
      elimination of extracellular pathogens, possessing a limited role in the
      orchestration of the immune response. This dogma has been challenged by recent
      lines of evidence demonstrating the expression of an increasing number of
      cytokines and effector molecules by neutrophils. Moreover, in analogy with their
      "big brother" macrophages, neutrophils integrate the environmental signals and
      can be polarized towards an antitumoural or protumoural phenotype. Neutrophils
      are a major source of humoral fluid phase pattern recognition molecules and thus
      contribute to the humoral arm of innate immunity. Neutrophils cross talk and
      shape the maturation and effector functions of other leukocytes in a direct or
      indirect manner, through cell-cell contact or cytokine production, respectively.
      Therefore, neutrophils are integrated in the activation and regulation of the
      innate and adaptive immune system and play an important role in the resolution or
      exacerbation of diverse pathologies, including infections, chronic inflammation,
      autoimmunity and cancer.

PMID- 23553220
TI  - Psychosocial distress is prevalent in head and neck cancer patients.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study is to evaluate the levels of
      psychological distress in head and neck cancer patients using a validated
      screening tool. We aim to characterize distress in this cancer population and
      understand the factors driving distress levels. STUDY DESIGN: Review of
      prospectively gathered data. METHODS: A review of prospectively gathered data was
      undertaken from 89 head and neck cancer patients (HNC) who completed the Distress
      Thermometer and Problem List (DT) from the National Comprehensive Cancer Network
      (NCCN). RESULTS: Distress levels were high in the overall population. The level
      of distress was significantly greater in patients with a self-reported history of
      depression (P <.001), family concerns (P = .030), emotional concerns (P = .001)
      and physical concerns (P = .014). CONCLUSIONS: Psychosocial distress was found to
      be high in the HNC population. Factors associated with increased distress level
      included a self-reported history of depression, family concerns, emotional
      concerns, and physical concerns.

PMID- 23553221
TI  - In-depth proteome analysis of the rubber particle of Hevea brasiliensis (para
      rubber tree).
AB  - The rubber particle is a special organelle in which natural rubber is synthesised
      and stored in the laticifers of Hevea brasiliensis. To better understand the
      biological functions of rubber particles and to identify the candidate rubber
      biosynthesis-related proteins, a comprehensive proteome analysis was performed on
      H. brasiliensis rubber particles using shotgun tandem mass spectrometry profiling
      approaches-resulting in a thorough report on the rubber particle proteins. A
      total of 186 rubber particle proteins were identified, with a range in relative
      molecular mass of 3.9-194.2 kDa and in isoelectric point values of 4.0-11.2. The
      rubber particle proteins were analysed for gene ontology and could be categorised
      into eight major groups according to their functions: including rubber
      biosynthesis, stress- or defence-related responses, protein processing and
      folding, signal transduction and cellular transport. In addition to well-known
      rubber biosynthesis-related proteins such as rubber elongation factor (REF),
      small rubber particle protein (SRPP) and cis-prenyl transferase (CPT), many
      proteins were firstly identified to be on the rubber particles, including
      cyclophilin, phospholipase D, cytochrome P450, small GTP-binding protein,
      clathrin, eukaryotic translation initiation factor, annexin, ABC transporter,
      translationally controlled tumour protein, ubiquitin-conjugating enzymes, and
      several homologues of REF, SRPP and CPT. A procedure of multiple reaction
      monitoring was established for further protein validation. This comprehensive
      proteome data of rubber particles would facilitate investigation into molecular
      mechanisms of biogenesis, self-homeostasis and rubber biosynthesis of the rubber
      particle, and might serve as valuable biomarkers in molecular breeding studies of
      H. brasiliensis and other alternative rubber-producing species.

PMID- 23553223
TI  - Hair-on-end.

PMID- 23553222
TI  - Plant species and organ influence the structure and subcellular localization of
      recombinant glycoproteins.
AB  - Many plant-based systems have been developed as bioreactors to produce
      recombinant proteins. The choice of system for large-scale production depends on
      its intrinsic expression efficiency and its propensity for scale-up, post-harvest
      storage and downstream processing. Factors that must be considered include the
      anticipated production scale, the value and intended use of the product, the
      geographical production area, the proximity of processing facilities,
      intellectual property, safety and economics. It is also necessary to consider
      whether different species and organs affect the subcellular trafficking,
      structure and qualitative properties of recombinant proteins. In this article we
      discuss the subcellular localization and N-glycosylation of two commercially
      relevant recombinant glycoproteins (Aspergillus niger phytase and anti-HIV
      antibody 2G12) produced in different plant species and organs. We augment
      existing data with novel results based on the expression of the same recombinant
      proteins in Arabidopsis and tobacco seeds, focusing on similarities and subtle
      differences in N-glycosylation that often reflect the subcellular trafficking
      route and final destination, as well as differences generated by unique enzyme
      activities in different species and tissues. We discuss the potential
      consequences of such modifications on the stability and activity of the
      recombinant glycoproteins. 

PMID- 23553224
TI  - Good clinical practice in resource-limited settings: translating theory into
      practice.
AB  - A Good Clinical Practices (GCPs) course, based on the combination of theoretical
      modules with a practical training in real-life conditions, was held in 2010 in
      Burkina Faso. It was attended by 15 trainees from nine African, Asian, and Latin
      American countries. There were some discrepancies between the average good
      results at the end of the theoretical phase and the GCP application during the
      first days of the practical phase, underlying the difficulties of translating
      theoretical knowledge into good practices. Most of the findings were not
      unexpected and reflected the challenges commonly faced by clinical investigators
      in resource-poor contexts (i.e., the high workload at peripheral health
      facilities, the need to conciliate routine clinical activities with clinical
      research, and the risk of creating a double standard among patients attending the
      same health facility [free care for recruited patients versus user fees for non
      recruited patients with the same medical condition]). Even if limited in number
      and time, these observations suggest that a theoretical training alone may not be
      sufficient to prepare trainees for the challenges of medical research in real
      life settings. Conversely, when a practical phase immediately follows a
      theoretical one, trainees can immediately experience what the research
      methodology implicates in terms of work organization and relationship with
      recruited and non-recruited patients. This initial experience shows the
      complexity of translating GCP into practice and suggests the need to rethink the
      current conception of GCP training.

PMID- 23553225
TI  - The lab without walls: a deployable approach to tropical infectious diseases.
AB  - The Laboratory Without Walls is a modular field application of molecular biology
      that provides clinical laboratory support in resource-limited, remote locations.
      The current repertoire arose from early attempts to deliver clinical pathology
      and public health investigative services in remote parts of tropical Australia,
      to address the shortcomings of conventional methods when faced with emerging
      infectious diseases. Advances in equipment platforms and reagent chemistry have
      enabling rapid progress, but also ensure the Laboratory Without Walls is subject
      to continual improvement. Although new molecular biology methods may lead to more
      easily deployable clinical laboratory capability, logistic and technical
      governance issues continue to act as important constraints on wider
      implementation.

PMID- 23553226
TI  - Bed bug detection: current technologies and future directions.
AB  - Technologies to detect bed bugs have not kept pace with their global resurgence.
      Early detection is critical to prevent infestations from spreading. Detection
      based exclusively on bites is inadequate, because reactions to insect bites are
      non-specific and often misdiagnosed. Visual inspections are commonly used and
      depend on identifying live bugs, exuviae, or fecal droplets. Visual inspections
      are inexpensive, but they are time-consuming and unreliable when only a few bugs
      are present. Use of a dog to detect bed bugs is gaining in popularity, but it can
      be expensive, may unintentionally advertise a bed bug problem, and is not
      foolproof. Passive monitors mimic natural harborages; they are discreet and
      typically use an adhesive to trap bugs. Active monitors generate carbon dioxide,
      heat, a pheromone, or a combination to attract bed bugs to a trap. New
      technologies using DNA analysis, mass spectrometry, and electronic noses are
      innovative but impractical and expensive for widespread use.

PMID- 23553228
TI  - Toxoplasma gondii: bystander or cofactor in rheumatoid arthritis.
AB  - Parasitic infections may induce variable immunomodulatory effects and control of
      autoimmune disease. Toxoplasma gondii (T. gondii) is a ubiquitous intracellular
      protozoan that was recently associated with autoimmunity. This study was
      undertaken to investigate the seroprevalence and clinical correlation of anti-T.
      gondii antibodies in patients with rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE). We evaluated sera from European patients with RA (n = 125)
      and SLE (n = 164) for the prevalence of anti-T. gondii IgG antibodies (ATXAb), as
      well as other common infections such as Cytomegalovirus, Epstein-Barr, and
      Rubella virus. The rates of seropositivity were determined utilizing the LIAISON
      chemiluminescent immunoassays (DiaSorin, Italy). Our results showed a higher
      seroprevalence of ATXAb in RA patients, as compared with SLE patients [63 vs. 36
      %, respectively (p = 0.01)]. The rates of seropositivity of IgG against other
      infectious agents were comparable between RA and SLE patients. ATXAb
      seropositivity was associated with older age of RA patients, although it did not
      correlate with RA disease activity and other manifestations of the disease. In
      conclusion, our data suggest a possible link between exposure to T. gondii
      infection and RA.

PMID- 23553229
TI  - Transoral laser microsurgery for early glottic cancer as one-stage single
      modality therapy.
AB  - OBJECTIVES/HYPOTHESIS: A study was undertaken to determine the oncologic outcomes
      in a consecutive series of early glottic carcinomas treated with transoral CO2
      laser microsurgery (TLM) as a one-stage single-modality therapy, without any
      postoperative radiation therapy or retreatment with laser. We further evaluated
      correlations between the oncologic outcomes and clinicopathologic factors
      including tumor location and surgical margin. STUDY DESIGN: Retrospective
      analysis of medical records. METHODS: The medical records of 118 consecutive
      patients with early stage (T1, T2) glottic carcinoma who underwent TLM by a
      single surgeon as an initial treatment from 1997 to 2011 were retrospectively
      reviewed. The oncologic outcomes were evaluated, and correlations to
      clinicopathologic factors were analyzed. RESULTS: The 5-year disease-free
      survival, ultimate local control with laser alone, disease-specific survival,
      overall survival, and organ preservation rates were 87.9%, 94.2%, 99.0%, 92.2%,
      and 96.2%, respectively. Neither the reported surgical margin nor the extension
      of tumor to the anterior commissure, arytenoid, subglottis, and ventricle showed
      any significant impact on local control or survival. CONCLUSIONS: Transoral CO2
      laser microsurgery as one-stage single-modality therapy resulted in a high rate
      of local control and a high survival rate in selected cases of early glottic
      carcinoma, regardless of the location of tumor and histopathology report on the
      surgical margin.

PMID- 23553230
TI  - Two steps forward, one step back? Implications of the Supreme Court's health
      reform ruling for individuals with mental illness.

PMID- 23553231
TI  - Content analysis of reporting templates and free-text radiology reports.
AB  - The Radiological Society of North America (RSNA) has developed a set of templates
      for structured reporting of radiology results. To measure how much of the content
      of conventional narrative ("free-text") reports is covered by the concepts
      included in the RSNA reporting templates, we selected five reporting templates
      that represented a variety of imaging modalities and organ systems. From a sample
      of 8,275 consecutive, de-identified radiology reports from an academic medical
      center, we identified one corresponding imaging procedure code for each reporting
      template. The reports were annotated with RadLex and SNOMED CT terms using the
      BioPortal Annotator web service. The reporting templates we examined accounted
      for 17 to 49 % of the concepts that actually appeared in a sample of
      corresponding radiology reports. The findings suggest that the concepts that
      appear in the reporting templates occur frequently within free-text clinical
      reports; thus, the templates provide useful coverage of the "domain of discourse"
      in radiology reports. The techniques used in this study may be helpful to guide
      the development of reporting templates by identifying concepts that occur
      frequently in radiology reports, to evaluate the coverage of existing templates,
      and to establish global benchmarks for reporting templates.

PMID- 23553233
TI  - What are the health risks of untreated snoring without obstructive sleep apnea?

PMID- 23553235
TI  - Revision for periprosthetic fractures of the hip and knee.

PMID- 23553238
TI  - Theory of mind, insecure attachment and paranoia in adolescents with early
      psychosis and healthy controls.
AB  - OBJECTIVE: Impaired Theory of Mind (ToM) is found in adults with schizophrenia
      and is associated with paranoid symptoms. Insecure attachment is proposed to
      underlie impaired ToM as well as paranoia. Insight into associations between
      insecure attachment and impaired ToM skills may help clinicians and patients to
      understand interpersonal difficulties and use this knowledge to improve recovery.
      This study used a visual perspective-taking task to investigate whether cognitive
      ToM is already impaired in adolescents with early psychosis as compared to
      controls. Also investigated was whether perspective-taking and paranoia are
      associated with insecure (adult) attachment. METHODS: Thirty-two adolescent
      patients with early psychosis and 78 healthy controls participated in this cross
      sectional study design and completed the level 1 perspective-taking task,
      psychopathology assessments (CAPE, PANSS), paranoid thoughts (GPTS), attachment
      style (PAM) and the WASI vocabulary. RESULTS: Patients did not significantly
      differ in level-1 perspective-taking behaviour compared to healthy controls. No
      significant associations were found between perspective-taking, paranoia and
      attachment. Insecure attachment was significantly related to paranoid thoughts,
      after controlling for illness-related symptoms. CONCLUSION: No impairment of
      level-1 perspective-taking was found in adolescent patients with early psychosis
      compared to healthy controls. Results indicate that level-1 perspective-taking is
      not impaired during the early stages of psychotic illness. The association
      between paranoia and attachment support previous findings and provide further
      insight into the nature of psychotic symptoms. Understanding the role of
      attachment in paranoia may help patients and their care workers to gain insight
      into the reasons for the development or persistence of symptoms. Future research
      should compare early psychosis samples with more chronic samples to explore
      whether perspective-taking deteriorates during the course of the illness.

PMID- 23553239
TI  - Is the need for medications with calming effects ever going to disappear?

PMID- 23553240
TI  - Does abortion reduce the mental health risks of unwanted or unintended pregnancy?
      A re-appraisal of the evidence.
AB  - OBJECTIVE: There have been debates about the linkages between abortion and mental
      health. Few reviews have considered the extent to which abortion has therapeutic
      benefits that mitigate the mental health risks of abortion. The aim of this
      review was to conduct a re-appraisal of the evidence to examine the research
      hypothesis that abortion reduces rates of mental health problems in women having
      unwanted or unintended pregnancy. METHODS: Analysis of recent reviews (Coleman,
      2011; National Collaborating Centre for Mental Health, 2011) identified eight
      publications reporting 14 adjusted odds ratios (AORs) spanning five outcome
      domains: anxiety; depression; alcohol misuse; illicit drug use/misuse; and
      suicidal behaviour. For each outcome, pooled AORs were estimated using a random
      effects model. RESULTS: There was consistent evidence to show that abortion was
      not associated with a reduction in rates of mental health problems (p>0.75).
      Abortion was associated with small to moderate increases in risks of anxiety (AOR
      1.28, 95% CI 0.97-1.70; p<0.08), alcohol misuse (AOR 2.34, 95% CI 1.05-5.21;
      p<0.05), illicit drug use/misuse (AOR 3.91, 95% CI 1.13-13.55; p<0.05), and
      suicidal behaviour (AOR 1.69, 95% CI 1.12-2.54; p<0.01). CONCLUSIONS: There is no
      available evidence to suggest that abortion has therapeutic effects in reducing
      the mental health risks of unwanted or unintended pregnancy. There is suggestive
      evidence that abortion may be associated with small to moderate increases in
      risks of some mental health problems.

PMID- 23553241
TI  - The effect of continuous positive airway pressure on middle ear pressure.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the effect of continuous positive airway
      pressure (CPAP) on middle ear pressure in patients with obstructive sleep apnea
      syndrome (OSAS). STUDY DESIGN: Prospective clinical case-control study. METHODS:
      Seventy-eight patients with moderate and severe OSAS (the mean apnea-hypopnea
      indexes were 22.70 +/- 3.59 and 48.59 +/- 12.50, respectively) using CPAP (study
      group) and 60 patients with no sleep apnea syndrome (control group) were included
      in the study. Forty-two of the patients were female and 96 were male. The mean
      age in the study group was 47.38 +/- 6.23, whereas it was 46.10 +/- 11.96 in the
      control group (P > .05). The middle ear pressure of all study subjects was
      evaluated with tympanometry at the beginning of the study and 6 months later.
      Tympanometric measurements of both groups were compared. Furthermore, the same
      data for the study group were also evaluated according to CPAP pressure levels.
      RESULTS: The middle ear peak pressure values of the patients in the study group
      were significantly increased from -63.04 +/- 55.82 daPa to -39.6 +/- 27.72 daPa
      after 6 months (P < .01). The middle ear pressure in the control group was found
      to be -13.26 +/- 22.60 daPa at the beginning of the study and -13.60 +/- 38.82
      daPa after 6 months (P > .05). The mean middle ear pressure level was
      significantly higher in patients using CPAP at 12 to 14 cm H2 O pressure than in
      those using CPAP at 8 to 10 cm H2 O pressure (P < .05). CONCLUSIONS: There was a
      significant increase in the middle ear pressure of patients using CPAP regularly
      for 6 months. This increase was proportional to the pressure level of the CPAP
      device. LEVEL OF EVIDENCE: 3b.

PMID- 23553242
TI  - Analysis of the presence of the GJB6 mutations in patients heterozygous for GJB2
      mutation in Brazil.
AB  - Mutations in the GJB2 gene, mainly 35delG, are responsible for most autosomal
      recessive inherited genetic hearing loss. The audiometric standard of these
      hearing losses remains inconsistent and other genes, such as GJB6, have been
      involved in association with GJB2. The objective of the study was to identify the
      deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) in patients heterozygous for
      35delG/GJB2 and analyze the phenotype they present. 101 patients with mild to
      profound degree of sensorineural hypoacusis were evaluated. The allele-specific
      PCR technique was used to identify 35delG. The del(GJB6-D13S1830) and del(GJB6
      D13S1854) were identified through the PCR multiplex technique. 90% of the
      subjects presented a normal genotype for the analyzed mutations; 6.93% were shown
      to be heterozygous for 35delG/GJB2 and 1% presented compound heterozygosis
      GJB2/GJB6). The data found reinforced the hypothesis of an interaction of more
      than one gene as the cause of autosomal recessive genetic hearing loss and
      emphasized the importance of an early diagnosis for appropriate intervention.

PMID- 23553243
TI  - Incidence and clinical characteristics of prelaryngeal lymph node metastasis in
      papillary thyroid cancer.
AB  - There is little data that determine the clinical characteristics of prelaryngeal
      lymph nodes (PLN) metastasis in patients with papillary thyroid cancer (PTC). The
      aims of this prospective study were to evaluate the incidence and the clinical
      characteristics of metastasis to the PLN for PTC patients who underwent total
      thyroidectomy and prophylactic central neck dissection. Sixty-seven patients who
      underwent total thyroidectomy and prophylactic bilateral central lymph node neck
      dissection for PTC were enrolled. Central neck compartment was further divided
      into prelaryngeal, ipsilateral/contralateral paratracheal, and pretracheal
      regions. Clinicopathologic factors including age, sex, tumor size and location,
      extrathyroidal extension, and central and lateral nodal metastasis were
      evaluated. Of the 67 patients who underwent PLN dissection, 13 (19.4 %) had
      evidence of PLN metastasis. Tumor size was significantly larger in patients with
      PLN involvement (2.28 versus 1.12 cm; p = 0.020). Additionally, primary tumors
      larger than 1 cm, extrathyroidal extension, and isthmus involvement were more
      prevalent in PLN-positive patients. Patients with positive PLNs were also more
      frequently found to have lateral lymph node metastasis (23.1 vs. 1.9 %; p =
      0.021), pretracheal lymph node metastasis (76.9 vs. 27.8 %; p = 0.003), and
      bilateral central lymph node metastasis (38.5 vs. 11.1 %; p = 0.031) than PTC
      patients without PLN involvement. The incidence of PLN metastasis in PTC patients
      who underwent prophylactic central lymph node neck dissection was 19.4 %. PLN
      metastasis was associated with tumor size, extrathyroidal extension, isthmus
      involvement, and other compartment lymph node metastasis.

PMID- 23553244
TI  - Coexistence of scutum defect and facial canal dehiscence.
AB  - In this study, we have discussed the facial canal dehiscence rates in patients
      with scutum defect, who had undergone surgery with the diagnosis of chronic
      otitis media with or without cholesteatoma. The operation records of 154 patients
      who had undergone tympanomastoidectomy with the diagnosis of chronic otitis media
      with or without cholesteatoma were retrospectively analyzed. Scutum defect was
      investigated by inspection under direct high magnification following
      tympanomeatal flap elevation during the operation. Facial canal dehiscence was
      evaluated by inspection and through palpation by blunt picking after the
      pathological tissues had been removed. The rate of scutum defect was determined
      as 29.22% (45 out of 154 patients), and the rate of facial canal dehiscence was
      determined as 22.07% (34 out of 154 patients). While facial canal dehiscence was
      encountered in 55.55% of the patients with scutum defect, this rate was
      determined as 8.25% in patients without scutum defect. While the tympanic segment
      was the most commonly affected segment of the facial canal, isolated mastoid
      segment involvement was encountered in only 1 (2.94%) patient. The presence of
      scutum defect is a significant finding for the prediction of the extent of the
      disease and facial canal dehiscence. Thus, the surgeon should pay more attention
      to avoid facial nerve injury during the operation in the patient in whom a scutum
      defect is detected.

PMID- 23553245
TI  - Current periprocedural anticoagulation in transcatheter aortic valve replacement:
      could bivalirudin be an option? Rationale and design of the BRAVO 2/3 studies.
AB  - Transcatheter aortic valve replacement (TAVR) is considered an important option
      in the management of patients with critical aortic valve stenosis that are either
      inoperable or have a high surgical risk. Despite continued advances in the
      procedural aspects of TAVR and decreasing complications rates, the risks of major
      vascular complications and stroke remain significant, which may in turn confer
      worse clinical outcomes and impact morbidity and mortality. In this review, we
      outline certain limitations of the currently recommended periprocedural
      anticoagulation in TAVR, namely unfractionated heparin that is guided by
      activated clotting times and protamine use if the bleeding risk is high. We will
      explore the potential for bivalirudin in this setting, which has become a
      frontrunner in acute coronary syndrome management because of favorable
      pharmacokinetics and lower bleeding complications. Finally, we will describe an
      ongoing large multicenter multinational trial that compares intravenous
      bivalirudin to unfractionated heparin during TAVR procedures using standardized
      clinical endpoints.

PMID- 23553246
TI  - Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the
      ASA low-response prevalence in CVD, CAD and PAD.
AB  - Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events
      in patients with atherosclerosis, a substantial number of incidents continue to
      occur. As only limited data exist we evaluated the antiplatelet effectiveness of
      ASA in patients with different manifestations of atherosclerosis as in
      cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD).
      For the evaluation of the antiplatelet effectiveness of ASA we used whole blood
      aggregometry (Chrono-log Model 590). The patients in the different subgroups
      received ASA 100, 200 or 500 mg daily. We analysed 737 consecutive patients: 47.5
      % with CVD, 33.6 % with CAD, and 18.9 % with PAD. We identified 28.0 % of the
      CVD, 18.1 % of the CAD and 21.6 % of the PAD patients to be ASA low-responder
      (ALR). Comparing subgroups treated with 100 mg ASA, 36.4 % were ALR in the CVD
      group as were 13.1 % of the CAD and 21.6 % of the PAD patients. Multivariate
      regression analysis revealed an odds ratio for being ALR of 4.50 (95 % confidence
      interval (CI) 1.70-11.9) when 100 mg and of 2.97 (95 % CI 1.58-5.60) when 200 mg
      ASA was taken compared to a dose of 500 mg. Despite the proven benefits of
      antiplatelet therapy in the secondary prevention of atherosclerotic disease,
      current antiplatelet management is suboptimal as up to 36 % of patients failed to
      achieve an adequate platelet inhibitory effect. Our findings may explain, at
      least in part, the high rates of cardiovascular events observed in the course of
      atherothrombotic disease and support the need to improve antiplatelet therapy. 

PMID- 23553247
TI  - Safety and efficacy of simultaneous bilateral carotid angioplasty and stenting.
AB  - In this study, we aimed to evaluate the safety and feasibility of simultaneous
      bilateral carotid artery stenting (BCAS) compared with staged BCAS in patients
      with bilateral atherosclerotic carotid stenosis (BCS). From January 2004 to March
      2012, 68 patients who underwent BCAS were identified from the Nanjing Stroke
      Registry Program. Of these patients, 42 (61.8 %) underwent simultaneous BCAS
      (simultaneous group), and 26 (38.2 %) underwent staged BCAS (staged group). We
      compared demographic data, major vascular risk factors, procedural parameters,
      and 30 day outcomes between the simultaneous and staged groups. No significant
      differences were detected in baseline data between the groups. Patients in the
      simultaneous group had a lower post-operative systolic pressure compared with the
      staged group (119.1 +/- 16.1 vs. 130.2 +/- 17.5 mmHg, P = 0.009). Technical
      success was 100 % of patients in the simultaneous group and 98.1 % in the staged
      group. Hemodynamic depression was observed in 57.4 % of procedures, with no
      significant difference between groups in the rate of HD. Four (5.9 %) patients
      had neurological complications within 30 days, including two cases of
      hyperperfusion syndrome in the simultaneous group, and two ischemic events in the
      staged group. There was no significant difference in the 30 day complication rate
      between the simultaneous and staged groups (4.8 vs. 7.7 %, P = 0.633).
      Simultaneous BCAS may be safe and feasible for most patients with BCS, with a
      similar 30 day complication rate to staged BCAS. Multicenter randomized control
      studies with larger sample sizes are warranted to further explore the safety and
      efficacy of simultaneous BCAS. 

PMID- 23553250
TI  - Imaging mass spectrometry: a new tool for kidney disease investigations.
AB  - Matrix-assisted laser desorption ionization (MALDI)-profiling and imaging mass
      spectrometry are promising technologies for measuring hundreds of different
      molecules directly on tissues. For instance, small molecules, drugs and their
      metabolites, endogenous lipids, carbohydrates and complex peptides/proteins can
      be measured at the same time without significant disruption of sample integrity.
      In this review, the potential of MALDI-profiling/imaging technologies in disease
      proteomics, drug action and studies of cellular processes in the context of
      kidney tissue is described. Spatial and sequence information obtained in tissue
      MALDI-profiling/imaging studies can be correlated with other mass spectrometry
      based techniques, auxiliary imaging technologies and routine (immuno)
      histochemical staining. 

PMID- 23553251
TI  - Do survivors of acute neurologic injury remember their stay in the neuroscience
      intensive care unit?
AB  - BACKGROUND: Patients in medical, surgical, and trauma intensive care units (ICUs)
      are at risk for later development of symptoms of post-traumatic stress disorder
      (PTSD). Because acute brain injury can impair recall; we sought to show that
      neuroscience patients undergoing prolonged neuroscience ICU admission have
      limited memory of their ICU stay and thus are less likely to develop symptoms of
      PTSD. METHODS: We surveyed patients >18 years admitted for 10 days or more to our
      neuroscience ICU over a 10-year period. RESULTS: The survey response rate was
      50.5% (47/93). Forty percent (19/47) of respondents presented with coma. Recall
      of details of the ICU admission was limited. Fewer than 10% of patients who
      required mechanical ventilation recalled being on a ventilator. Only five
      patients (11%) had responses suggestive of possible post-traumatic stress
      syndrome. The most commonly experienced symptoms following discharge were
      difficulty sleeping, difficulty with concentration, and memory loss. CONCLUSION:
      Patients requiring prolonged neuroscience ICU admission do not appear to be
      traumatized by their ICU stay.

PMID- 23553252
TI  - Habitat characterization of western hoolock gibbons Hoolock hoolock by examining
      home range microhabitat use.
AB  - Conserving a species depends on an understanding of its habitat requirements.
      Primatologists often characterize the habitat requirements of primates using
      macroscale population-based approaches relying on correlations between habitat
      attributes and population abundances between sites with varying levels of
      disturbance. This approach only works for species spread between several
      populations. The populations of some primates do not fulfill these criteria,
      forcing researchers to rely on individual-based (microscale) rather than
      population-based approaches for habitat characterization. We examined the
      reliability of using micro-scale habitat characterizations by studying the
      microhabitat preferences of a group of wild western hoolock gibbons (Hoolock
      hoolock) in order to compare our results to the habitat preferences of western
      hoolock gibbons identified during a macroscale study of populations across
      Bangladesh. We used stepwise discriminant analysis to differentiate between the
      areas of low, medium, and high usage based on microhabitat characteristics (tree
      species availability, altitude, canopy connection, distance from forest edge, and
      levels of human disturbance). The gibbons used interior forest habitat with low
      food tree availability most frequently for sleeping and socializing, and used
      edge habitat containing high food tree availability for medium periods for
      feeding. These results indicate that the gibbons prefer interior forest but are
      frequently forced to visit the forest edge to feed. Therefore, the optimal
      habitat would be interior forest away from human disturbance with high sleeping
      tree and feeding-tree availability. These habitat preferences are consistent with
      the habitat attributes of Bangladesh's largest remaining western hoolock gibbon
      populations, which live in areas containing low agricultural encroachment and
      high food-tree availability. Microhabitat use studies can be used to characterize
      the habitat requirements of a species, but should include multiple scales of
      analysis wherever possible. 

PMID- 23553253
TI  - Long-term outcomes of surgery followed by radiation therapy for minor salivary
      gland carcinomas.
AB  - OBJECTIVES/HYPOTHESIS: Postoperative radiation therapy is often used in patients
      with high-risk salivary gland carcinomas. In this study we evaluated the outcomes
      and prognostic factors in patients with minor salivary gland cancers treated with
      adjuvant radiation therapy. STUDY DESIGN: Retrospective cohort study. METHODS: We
      performed a retrospective analysis of 90 patients treated with curative intent.
      Median follow-up was 71 months. Fifty-eight patients (64%) had adenoid cystic
      carcinomas, 22 (24%) had adenocarcinomas, and 10 (11%) had mucoepidermoid
      cancers. Primary disease site included 39 (43%) sinonasal, 35 (39%) oral cavity,
      10 (11%) oropharynx, and six (7%) others. Twenty-seven patients (30%) were
      treated with intensity-modulated radiation therapy. RESULTS: Eight local, four
      neck, and 24 distant relapses were detected. Local control rates at 5 and 10
      years were 90% and 88%, respectively. Advanced T stage was associated with worse
      local control. Distant metastasis rates were 24% and 28% at 5 and 10 years,
      respectively. Tumor stage, histology, perineural invasion, and lymphovascular
      space invasion were significant predictors of distant metastasis on univariate
      analysis. However, on multivariate analysis only the American Joint Committee on
      Cancer stage was significant. Overall survival rates were 76% and 63% at 5 and 10
      years, respectively. More advanced T stage and N stage correlated with worse
      overall survival. CONCLUSIONS: Tumor stage remains the best predictor for
      locoregional and distant disease control of minor salivary gland cancers.
      Postoperative radiation therapy for high-risk patients results in excellent long
      term locoregional disease control. Further work is needed to improve systemic
      control.

PMID- 23553255
TI  - Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion.
AB  - OBJECTIVES/HYPOTHESIS: Ostiomeatal complex (OMC) occlusion may play a role in the
      pathogenesis of some chronic rhinosinusitis (CRS) subgroups, but its role in
      diffuse mucosal inflammation is strongly debated. The association between
      radiological OMC occlusion and its draining sinuses in patients with eosinophilic
      rhinosinusitis (ECRS) compared to non-ECRS is investigated. STUDY DESIGN: Case
      control study. METHODS: Patients with CRS who underwent endoscopic sinus surgery
      were investigated. Preoperative computed tomography scans were evaluated.
      Structured histopathology reporting was performed. The study group was patients
      with high tissue eosinophil >10/high power fields (HPF), and the control group
      was patients with low tissue eosinophil <= 10/HPF. The radiological relationship
      of OMC occlusion to the draining sinuses was analyzed in each group. RESULTS:
      Seventy patients with a mean age of 49.7 +/- 14.1 years were analyzed. Forty-one
      (58.6%) patients had high tissue eosinophil >10/HPF. All patients with ECRS had
      maxillary disease, and there were 36.2% without OMC occlusion. There was no
      association of OMC occlusion to either the anterior ethmoid (ECRS: odds ratio
      [OR], 1.84; 95% confidence interval [CI], 0.24-14.14; P = .55; non-ECRS: OR,
      1.57; 95% CI, 0.34-7.33; P = .56) or frontal sinuses (ECRS: OR, 0.67; 95% CI,
      0.12-3.82; P = .65; non-ECRS: OR, 1.58; 95% CI, 0.45-5.54; P = .47). For patients
      with non-ECRS, maxillary sinus diseases was present in 96.2% of those with OMC
      occlusion and 50% of those without (OR, 25.0; 95% CI, 2.77-226.08; P < .001).
      CONCLUSIONS: OMC occlusion is not associated with draining sinuses for patients
      with ECRS. Simple surgical interventions directed at the OMC are unlikely to be
      of benefit to this CRS subgroup. LEVEL OF EVIDENCE: 3b.

PMID- 23553256
TI  - Photodeactivation paths in norbornadiene.
AB  - The first high level ab initio quantum-chemical calculations of potential energy
      surfaces (PESs) for low-lying singlet excited states of norbornadiene in the gas
      phase are presented. The optimization of the stationary points (minima and
      conical intersections) and the recalculation of the energies were performed using
      the multireference configuration interaction with singles (MR-CIS) and the
      multiconfigurational second-order perturbation (CASPT2) methods, respectively. It
      was shown that the crossing between valence V2 and Rydberg R1 states close to the
      Franck-Condon (FC) point permits an easy population switch between these states.
      Also, a new deactivation path in which the doubly excited state with (pi3)(2)
      configuration (DE) has a prominent role in photodeactivation from the R1 state
      due to the R1/DE and the DE/V1 conical intersections very close to the R1 and DE
      minima, respectively, was proposed. Subsequent deactivation from the V1 to the
      ground state goes through an Olivucci-Robb-type conical intersection that adopts
      a rhombic distorted geometry. The deactivation path has negligible barriers,
      thereby making ultrafast radiationless decay to the ground state possible.

PMID- 23553257
TI  - Complications in total shoulder arthroplasty.

PMID- 23553258
TI  - An unexpected subglottic foreign body diagnosed two years after aspiration.

PMID- 23553259
TI  - The effects of topical anesthetic on swallowing during nasoendoscopy.
AB  - OBJECTIVES/HYPOTHESIS: To assess the effects of a typical otolaryngologic dose of
      1 mL of 4% lidocaine on penetration aspiration scale scores and participant
      discomfort during flexible endoscopic evaluation of swallowing. STUDY DESIGN: A
      prospective pilot study. METHODS: Twenty healthy participants consumed 12
      swallows consisting of graduated volumes of milk, water, pudding, and cracker in
      anesthetized and nonanesthetized conditions. Each participant was randomly
      selected to begin with the anesthetized or nonanesthetized condition. Each
      participant returned within 7 days to repeat the study in the other condition.
      Digital recordings of their evaluations were scored via the penetration
      aspiration scale in a blinded fashion. Participants recorded their discomfort and
      tolerance of each flexible endoscopic evaluation of swallowing. RESULTS: The
      anesthetized condition yielded significantly worse swallowing function (P = .001)
      than the nonanesthetized condition. The nonanesthetized condition yielded greater
      discomfort and pain during the procedure (P = .006, .018), greater pain during
      insertion and removal of the endoscope (P = .002, .003) and less overall
      tolerance (P = .016) than the anesthetized condition. CONCLUSIONS: A typical
      otolaryngologic anesthetic dose of 1 mL of 4% lidocaine during flexible
      endoscopic evaluation of swallowing predisposed healthy young adults to higher
      penetration aspiration scale scores (less safe swallowing) than the
      nonanesthetized condition; however, the anesthetic reduced discomfort and
      provided better overall tolerance. Future studies need to evaluate the effects of
      lower doses of lidocaine (0.2 and 0.5 mL) on swallowing function and comfort.

PMID- 23553260
TI  - Survey of Anaplasmataceae bacteria in sheep from Senegal.
AB  - PURPOSE: The authors studied the role of bacteria belonging to Anaplasmataceae
      family as the causes of acute illnesses of sheep in West Africa. METHODS: We
      examined and sampled 120 febrile sheep in two regions of Senegal for this study.
      The DNA extracted from these blood samples was tested by PCR using two pairs of
      primers (groEL-based and 16S rRNA gene-based). RESULTS: In 52/120 samples, the
      microscopic examination revealed intraerythrocytic and/or intraphagocytic
      spherical inclusions. In 48/52 cases, we succeeded in identifying the bacterial
      agent: in 38 cases, it was Anaplasma ovis; in six cases, it was Ehrlichia
      ruminantium; in two cases, Anaplasma phagocytophilum; in one case, Anaplasma
      platys; and in one case, a yet uncultured Anaplasma sp. closely related to A.
      phagocytophilum. CONCLUSIONS: Our studies demonstrated the great variety of
      pathogenic bacteria from the Anaplasmataceae family in the blood of clinically
      ill sheep. A. ovis was identified unexpectedly often. For the first time, A.
      phagocytophilum was found in sub-Saharan Africa, and its further epidemiology may
      be now reconsidered. The roles of canine pathogen, A. platys, and yet undescribed
      Anaplasma sp. "Badioure" in ovine pathology should be more closely studied.

PMID- 23553261
TI  - Linking processes and outcomes: a key strategy to prevent and report harm from
      venous thromboembolism in surgical patients.

PMID- 23553262
TI  - Metastatic malignant melanoma to the colon: a case report and review of the
      literature.

PMID- 23553264
TI  - Role of environmental factors in Cryptococcal meningitis in immunocompetent
      individuals.

PMID- 23553263
TI  - Maltreatment profiles among incarcerated boys with callous-unemotional traits.
AB  - Callous-unemotional (CU) traits in youth are believed to be a developmental
      precursor to adult psychopathy, tapping its affective dimension. There is growing
      support for the existence of variants of psychopathy that can be distinguished
      based on the presence of anxiety, maltreatment histories, and comorbid
      psychopathology. The purpose of the present study was to examine whether primary
      and secondary variants of CU traits could be differentiated according to their
      experiences of distinct types of childhood maltreatment among a sample of 227
      incarcerated adolescent boys. Results indicated that variants of youth scoring
      high on CU traits could be identified which were consistent with theory and prior
      research. Greater sexual abuse histories, violent and property delinquency, and a
      sexually motivated index offense distinguished secondary variants, whereas
      greater neglect distinguished primary variants of youth with CU traits.
      Psychopathy variants were behaviorally indistinguishable with respect to their
      levels of aggression and drug delinquency, although they differed in several
      important ways from youth scoring low on CU traits. Variants also showed distinct
      patterns of scores on the measure of CU traits. These findings are important to
      informing developmental theories of psychopathy and have practical and policy
      implications for intervening with maltreated and antisocial youth.

PMID- 23553265
TI  - Cerebral venous sinus thrombosis in a child with iron-deficiency anemia.

PMID- 23553267
TI  - Sinonasal adenoid cystic carcinoma: comprehensive analysis of incidence and
      survival from 1973 to 2009.
AB  - OBJECTIVES/HYPOTHESIS: Sinonasal adenoid cystic carcinoma (SNACC) is a rare
      malignancy that most commonly arises in the maxillary sinus. Characteristics of
      SNACC are slow growth, perineural invasion, and long clinical course. Because it
      is a rare tumor, population-based studies are limited. We analyzed the incidence
      and survival for SNACC using a national population-based database. STUDY DESIGN:
      Retrospective cohort study using national cancer database. METHODS: The United
      States National Cancer Institute's Surveillance, Epidemiology, and End Results
      (SEER) registry was utilized to calculate incidence and survival trends for SNACC
      between 1973 and 2009. Patient data were then analyzed according to age, sex, and
      race. Incidence trends were studied for the last 30 years, and survival outcomes
      were compared across the different demographic parameters. RESULTS: A total of
      412 cases of SNACC were identified (57.52% female). Incidence trend analysis
      revealed a significant decrease in yearly rates from 1973 to 2009 for the overall
      population, females, whites, blacks, and "others." Overall 5-year survival for
      SNACC was 68.80%, 10-year survival was 48.03%, and 20-year survival was 22.39%.
      Significant differences in survival outcomes were noted between whites, blacks,
      and "others." "Others" had the best 20-year survival outcomes. CONCLUSIONS: The
      overall incidence of SNACC is declining. Sex and race seem to influence the
      overall survival for this rare tumor. Future studies need to be conducted to
      investigate these dynamic trends related to SNACC.

PMID- 23553269
TI  - A system for extracting study design parameters from nutritional genomics
      abstracts.
AB  - The extraction of study design parameters from biomedical journal articles is an
      important problem in natural language processing (NLP). Such parameters define
      the characteristics of a study, such as the duration, the number of subjects, and
      their profile. Here we present a system for extracting study design parameters
      from sentences in article abstracts. This system will be used as a component of a
      larger system for creating nutrigenomics networks from articles in the
      nutritional genomics domain. The algorithms presented consist of manually
      designed rules expressed either as regular expressions or in terms of sentence
      parse structure. A number of filters and NLP tools are also utilized within a
      pipelined algorithmic framework. Using this novel approach, our system performs
      extraction at a finer level of granularity than comparable systems, while
      generating results that surpass the current state of the art.

PMID- 23553268
TI  - Phase 2 study of dose-intense temozolomide in recurrent glioblastoma.
AB  - BACKGROUND: Among patients with glioblastoma (GBM) who progress on standard
      temozolomide, the optimal therapy is unknown. Resistance to temozolomide is
      partially mediated by O(6)-methylguanine-DNA methyltransferase (MGMT). Because
      MGMT may be depleted by prolonged temozolomide administration, dose-intense
      schedules may overcome resistance. METHODS: This was a multicenter, phase 2,
      single-arm study of temozolomide (75-100 mg/m(2)/day) for 21 days of each 28-day
      cycle. Patients had GBM in first recurrence after standard therapy. The primary
      end point was 6-month progression-free survival (PFS6). RESULTS: Fifty-eight
      participants were accrued, 3 of whom were ineligible for analysis; one withdrew
      before response assessment. There were 33 men (61%), with a median age of 57
      years (range, 25-79 years) and a median Karnofsky performance score of 90 (range,
      60-100). Of 47 patients with MGMT methylation results, 36 (65%) had methylated
      tumors. There were 7 (13%) partial responses, and PFS6 was only 11%. Response and
      PFS did not depend on MGMT status; MSH2, MLH1, or ERCC1 expression; the number of
      prior temozolomide cycles; or the time off temozolomide. Treatment was well
      tolerated, with limited grade 3 neutropenia (n = 2) or thrombocytopenia (n = 2).
      CONCLUSIONS: Dose-intense temozolomide on this schedule is safe in recurrent GBM.
      However, efficacy is marginal and predictive biomarkers are needed.

PMID- 23553270
TI  - Ex vivo electromechanical reshaping of costal cartilage in the New Zealand white
      rabbit model.
AB  - OBJECTIVES/HYPOTHESIS: Determine the effective electromechanical reshaping (EMR)
      parameters for shape change and cell viability in the ex vivo rabbit costal
      cartilage model. STUDY DESIGN: Ex vivo animal study combined with computer
      modeling to guide electrode placement and polarity selection. METHODS: Rabbit
      costal cartilages were secured in a jig that approximated the shape of the rabbit
      auricle framework. Finite element modeling was used to select the initial
      electrode geometry, polarity, spacing, and estimate dosimetry parameters. Porcine
      costal cartilage was utilized to refine the selection of dosing parameters.
      Parametric analysis was performed to determine the effect of voltage and
      application time on tissue shape change. Next, rabbit rib cartilage was reshaped,
      varying voltage and application time to identify the lowest parameters to produce
      acceptable shape change mimicking native auricular cartilage. Acceptable
      qualitative shape change was determined on a five-point Likert scale analyzed
      using one-way general linear analysis of variance. Confocal microscopy with
      live/dead cell viability analysis determined the degree of injury and the
      distribution of live and dead cells. RESULTS: The minimum acceptable deformation
      of rabbit costal cartilage was found at 4 V-3 minutes. Viability analysis of
      cartilage reshaped at 4 V-3 minutes demonstrates cell injury extending 2 mm away
      from each electrode with viable cells found between the electrodes. CONCLUSIONS:
      The EMR parameters of 4 V-3 minutes demonstrates appropriate shape change
      producing grafts that resemble the native auricle and contains the viable cells
      adequate for clinical evaluation. The rabbit auricular reconstruction model using
      EMR is a feasible one.

PMID- 23553271
TI  - JACOB: an enterprise framework for computational chemistry.
AB  - Here, we present just a collection of beans (JACOB): an integrated batch-based
      framework designed for the rapid development of computational chemistry
      applications. The framework expedites developer productivity by handling the
      generic infrastructure tier, and can be easily extended by user-specific
      scientific code. Paradigms from enterprise software engineering were rigorously
      applied to create a scalable, testable, secure, and robust framework. A
      centralized web application is used to configure and control the operation of the
      framework. The application-programming interface provides a set of generic tools
      for processing large-scale noninteractive jobs (e.g., systematic studies), or for
      coordinating systems integration (e.g., complex workflows). The code for the
      JACOB framework is open sourced and is available at: www.wallerlab.org/jacob.

PMID- 23553273
TI  - Hepaticojejunostomy using short-limb Roux-en-Y reconstruction.
AB  - IMPORTANCE: When performing biliary reconstruction, one of the long-standing
      tenets of surgery is that Roux-en-Y (RY) reconstruction should use a long hepatic
      limb to decrease the risk for postoperative cholangitis. However, this practice
      is not well supported and may also make postoperative biliary endoscopy
      difficult. While some authors recommend Roux limbs of up to 75 cm, we have
      routinely used a Roux length of 20 cm to facilitate possible postoperative
      endoscopic access. OBJECTIVE: To review our experience with short-limb RY
      hepaticojejunostomy (HJ) and examine the short-term and long-term outcomes
      following this procedure, as well as the success of future biliary interventions.
      DESIGN: Retrospective medical record review of all patients who underwent short
      limb RYHJ by 2 surgeons (N.N.N. and S.D.C.). SETTING: Tertiary care, university
      affiliated teaching hospital. PARTICIPANTS: One hundred patients who underwent
      RYHJ were identified, with 30 of those patients being excluded owing to creation
      of an RYHJ to intrahepatic bile ducts with concomitant liver resection. MAIN
      OUTCOMES AND MEASURES: Patient records were reviewed to determine the incidence
      of postoperative cholangitis and biliary stricture. Secondary outcomes were the
      need for postoperative biliary endoscopy and success rates for endoscopic biliary
      interventions. RESULTS Seventy patients underwent short-limb RYHJ over an 11-year
      period (2001-2012). Indications included benign stricture (n = 18), malignant
      stricture (n = 12), choledochal cyst (n = 5), choledocholithiasis (n = 3),
      idiopathic cholangitis (n = 2), and deceased donor or live donor liver transplant
      (n = 30). Seven patients, including 4 liver transplant patients, developed
      clinical or radiographic evidence of postoperative biliary stricture, and all
      patients underwent successful endoscopic cholangiography. Four of these patients
      required dilation and/or stone extraction, which were accomplished endoscopically
      in all cases. CONCLUSIONS AND RELEVANCE: Short-limb RYHJ is safe and associated
      with a low incidence of postoperative complications. In addition, biliary
      intervention, when indicated, can be performed endoscopically with a high degree
      of success. In the absence of any evidence demonstrating longer limbs to be
      superior, we recommend using short-limb RY reconstruction for HJ.

PMID- 23553272
TI  - The variant histone H2A.V of Drosophila--three roles, two guises.
AB  - Histone variants play important roles in eukaryotic genome organization, the
      control of gene expression, cell division and DNA repair. Unlike other organisms
      that employ several H2A variants for different functions, the parsimonious fruit
      fly Drosophila melanogaster gets along with just a single H2A variant, H2A.V.
      Remarkably, H2A.V unites within one molecule features and functions of two
      different mammalian H2A variants, H2A.Z and H2A.X. Accordingly, H2A.V is involved
      in diverse functions, as an element of a class of active promoter structure, as a
      foundation for heterochromatin assembly and as a DNA damage sensor. Here, we
      comprehensively review the current knowledge of this fascinating histone variant.

PMID- 23553275
TI  - Waist circumference is associated with carotid intima media thickness in
      peritoneal dialysis patients.
AB  - PURPOSE: Atherosclerosis is responsible for the high mortality rate in end-stage
      renal disease patients. Defining risk factors for atherosclerosis may lead to
      reduction in cardiovascular disease through modification of these factors.
      Peritoneal dialysis (PD) patients are subjected to high glucose loads on a daily
      basis, which results in considerable weight gain and an increase in waist
      circumference (WC). WC as an indicator of abdominal obesity is a risk factor for
      atherosclerosis in the general population. Carotid artery intima media thickness
      (CIMT) measurement is a reliable method for the detection of early
      atherosclerosis. The aim of this study was to investigate the relationship
      between WC and CIMT and to define risk factors associated with CIMT in PD
      patients. METHODS: Fifty-five PD patients and 40 healthy controls were included.
      Atherosclerosis was assessed using measurement of CIMT. Fasting blood was
      collected for analysis. Anthropometric parameters (age, weight, BMI, and WC) were
      measured. RESULTS: Peritoneal dialysis patients had higher WC (93.9 +/- 1.7 vs.
      87.3 +/- 1.2 cm, p < 0.05) and CIMT (0.70 +/- 0.02 vs. 0.57 +/- 0.01 mm, p <
      0.01) than the control group. On univariate analysis, age, WC, plaque formation,
      and D/P creatinine were positively correlated with CIMT, whereas residual renal
      function, albumin, ultrafiltration volume, and D/D0 glucose were negatively
      correlated. On multivariate analysis, only age, WC, and plaque formation showed
      correlation (p < 0.001). CONCLUSIONS: Carotid artery intima media thickness is
      associated with age, plaque formation, and WC in PD patients. WC measurement is a
      simple, inexpensive, reproducible, and reliable method of evaluating
      atherosclerosis risk in PD patients and should be assessed at every visit.
      Appropriate counsel should be provided to patients with greater WC who are deemed
      to be at risk for atherosclerosis.

PMID- 23553276
TI  - Treatment for hepatitis C virus-induced portal hypertension in leukemic children.
AB  - Children with acute leukemia are at high risk of hepatitis C infection, either by
      immunosuppression secondary to chemotherapy or by multiple transfusions of blood
      products during the course of the disease. Hepatitis C virus (HCV) infection
      constitutes a major problem during management of acute leukemia due to resultant
      portal hypertension or bleeding esophageal varices. Chronic HCV infection is a
      major cause of liver cirrhosis and hepatocellular carcinoma in leukemic
      survivors. The effect of amlodipine treatment on children with acute
      lymphoblastic leukemia (ALL) having portal hypertension secondary to HCV
      infection during maintenance chemotherapy has been studied. Sixty male children
      (mean age 11.83 +/- 1.1 years) with ALL in remission and have HCV infection were
      included. Diagnosis of HCV infection was confirmed by real-time PCR. Thirty
      patients received 5 mg amlodipine orally per day for 4 weeks and compared to
      another 30 patients received placebo therapy and 30 age- and sex-matched children
      as a control group. Amlodipine significantly reduced the elevated portal blood
      pressure to normal level in doses which did not interfere with mechanism of
      action of chemotherapy (p <= 0.001). Treatment with amlodipine can be used to
      control portal hypertension in leukemic children having HCV-induced portal
      hypertension. HCV in leukemics could be virtually eliminated by proper testing of
      the blood transfusion pool.

PMID- 23553277
TI  - Chiari type I malformation: presenting as chronic cough in older children.
AB  - To highlight an unusual cause of chronic cough, we present two cases of chronic
      cough in older children referred to a pediatric otolaryngology outpatient clinic
      with persistent symptoms despite extensive previous workup and treatment. Cranial
      neuropathy was identified in each case. As a result, magnetic resonance imaging
      was performed revealing Chiari type I malformation. In each case, surgical
      decompression provided symptom improvement. Chronic cough is a rare presenting
      symptom in children with Chiari type I malformation. We emphasize the
      significance of awareness for unusual cases of cough to aid in the correct
      identification and treatment in children.

PMID- 23553278
TI  - A brief review of useful tips for publishing your scientific manuscript.

PMID- 23553280
TI  - Macromitophagy is a longevity assurance process that in chronologically aging
      yeast limited in calorie supply sustains functional mitochondria and maintains
      cellular lipid homeostasis.
AB  - Macromitophagy controls mitochondrial quality and quantity. It involves the
      sequestration of dysfunctional or excessive mitochondria within double-membrane
      autophagosomes, which then fuse with the vacuole/lysosome to deliver these
      mitochondria for degradation. To investigate a physiological role of
      macromitophagy in yeast, we examined how theatg32Delta-dependent mutational block
      of this process influences the chronological lifespan of cells grown in a
      nutrient-rich medium containing low (0.2%) concentration of glucose. Under these
      longevity-extending conditions of caloric restriction (CR) yeast cells are not
      starving. We also assessed a role of macromitophagy in lifespan extension by
      lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR
      conditions. Our findings imply that macromitophagy is a longevity assurance
      process underlying the synergistic beneficial effects of CR and LCA on yeast
      lifespan. Our analysis of how the atg32Delta mutation influences mitochondrial
      morphology, composition and function revealed that macromitophagy is required to
      maintain a network of healthy mitochondria. Our comparative analysis of the
      membrane lipidomes of organelles purified from wild-type and atg32Delta cells
      revealed that macromitophagy is required for maintaining cellular lipid
      homeostasis. We concluded that macromitophagy defines yeast longevity by
      modulating vital cellular processes inside and outside of mitochondria.

PMID- 23553282
TI  - Public safety, mental disorders, and guns.

PMID- 23553281
TI  - Haemolytic anaemia after oral artemether-lumefantrine treatment in a patient
      affected by severe imported falciparum malaria.
AB  - Artemisinin and its derivatives are essential components of artemisinin-based
      combination therapies for treating severe falciparum malaria. In this paper, we
      describe the occurrence of haemolysis after oral artemether-lumefantrine
      treatment. To the best of our knowledge, this is the second reported case of a
      patient affected by severe falciparum malaria with haemolytic anaemia that is
      likely associated with oral artemether-lumefantrine treatment. 

PMID- 23553283
TI  - Sinonasal undifferentiated carcinoma and esthesioneuroblastoma recurring as
      nonintestinal adenocarcinoma.
AB  - Numerous distinct neoplasms are encountered at the anterior cranial base.
      Management of these primary tumors and their locoregional recurrences are
      dictated by the histopathologic diagnosis. We present two unusual cases of extra
      axial anterior cranial base malignancies with locoregional recurrence where the
      recurrent tumor encountered was of a distinct histopathologic type. While rare,
      this report highlights the possibility of encountering a distinct tumor type in
      the posttreatment surveillance of patients with anterior cranial base
      malignancies.

PMID- 23553284
TI  - Myriad ocular manifestations of one of the oldest human scourges in the eye.

PMID- 23553285
TI  - The relationship between serum levels of angiogenin, bFGF, VEGF, and ocular
      involvement in patients with Behcet's disease.
AB  - OBJECTIVES: The aim of this study was to investigate the possible role of
      angiogenin, vascular endothelial growth factor, (VEGF) and basic fibroblast
      growth factor (bFGF) in the pathogenesis of BD. DESIGN AND METHODS: Sixty-five
      patients with BD and 21 healthy control subjects were included in the study, and
      serum angiogenin, bFGF, and VEGF concentrations were measured by using in-vitro
      enzyme immunoassay (ELISA) kits according to the manufacturer's instructions.
      RESULTS: The median serum angiogenin level was significantly higher in patients
      with BD (391.8; range:151.6-594.8 pg/ml) than controls (298.8; range:241.9-449.6
      pg/ml) (p = 0.001). The levels were similar in both ocular and non-ocular BD
      patients (p = 0.537). The mean serum bFGF level was higher in patients with BD
      (38.8 +/- 12.3 pg/ml) than controls (33.2 +/- 11.3 pg/ml); the median serum VEGF
      level was also higher in BD patients (239.7; range:53-991.3 pg/ml) than controls
      (189.4; range:53.6-357.9 pg/ml). But these differences were not statistically
      significant. Serum bFGF and VEGF levels were also not different statistically in
      ocular and non-ocular Behcet's patients. There was no statistically significant
      relationship between serum angiogenin, bFGF, and VEGF levels and the presence of
      active eye disease or anatomic location of uveitis. While there was a correlation
      of borderline significance in angiogenin levels between the patients with
      anterior uveitis and panuveitis (p = 0.053), we did not obtain any correlation
      between serum angiogenin, bFGF, and VEGF levels and the duration of BD.
      CONCLUSIONS: This study suggests that angiogenin may be associated with
      pathophysiology of BD, and highlights the need of further investigation of the
      role of angiogenin, bFGF, and VEGF serum levels in BD susceptibility and its
      clinical manifestations.

PMID- 23553286
TI  - Two-year results of combined intravitreal ranibizumab and photodynamic therapy
      for polypoidal choroidal vasculopathy.
AB  - BACKGROUND: To clarify the efficacy of combined therapy with intravitreal
      ranibizumab injections and photodynamic therapy (PDT) in patients with
      symptomatic polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively
      reviewed 57 treatment-naive eyes of 57 patients. Thirty-two patients were treated
      with standard fluence PDT (PDT group), and 25 patients were treated with three
      consecutive monthly intravitreal injections of ranibizumab and standard fluence
      PDT (ranibizumab plus PDT group). All patients were followed for at least 24
      months. RESULTS: In the ranibizumab plus PDT group, the mean best-corrected
      visual acuity (BCVA) levels of decimal (logMAR equivalent) significantly improved
      from 0.30 (0.52) at baseline to 0.55 (0.26) at 24 months (P < 0.001). In the PDT
      group, the BCVA levels stabilized from 0.26 (0.58) at baseline to 0.25 (0.60) at
      24 months. The mean changes in the BCVA in the ranibizumab plus PDT group and the
      PDT group were improvement of 2.63 lines and decline of 0.16 lines respectively
      (P = 0.010). The mean number of PDTs at 24 months in the ranibizumab plus PDT
      group and the PDT group were 1.4 and 2.6 respectively. Increased subretinal
      hemorrhages were seen in eight (18.0 %) eyes, all of which were belonging to the
      PDT group. CONCLUSIONS: Combined intravitreal ranibizumab and PDT was
      significantly more effective in maintaining and improving VA for PCV patients
      compared with PDT monotherapy over 24 months.

PMID- 23553287
TI  - Assessment of age changes and repeatability for computer-based rod dark
      adaptation.
AB  - PURPOSE: To characterize the rate of rod-mediated sensitivity decline with age
      using a PC-driven cathode ray tube (CRT) monitor. To provide data regarding the
      repeatability of the technique. METHODS: Dark adaptation was monitored for 30 min
      following a minimum 30 % pigment bleach, using a white 1 degrees  stimulus
      (modulated at 1 Hz), presented 11 degrees  below fixation on a CRT monitor.
      Thirty-three subjects with no ocular pathology and normal fundus photographs were
      divided into two groups: older (>=45, n = 16) and younger (<45, n = 17). RESULTS:
      Rod recovery was assessed using component S2 of dark adaptation. S2 was
      significantly slower in the older (0.19 +/- 0.03 log cd.m(-2).min(-1)) compared
      with the younger group (0.23 +/- 0.03 log cd.m(-2).min(-1), t = -4.05, p <
      0.0003), despite no difference in visual acuity and fundus appearance. Faster
      rates of S2 recovery were correlated with lower threshold at 30 min (T30) (r = 
      0.49). Correlation coefficients between first and second measurements for S2 and
      T30 were 0.49 (p < 0.009) and 0.84 (p < 0.0001) respectively. The coefficient of
      repeatability was 0.07 log cd.m(-2).min(-1) for S2 and 0.35 log cd.m(-2) for T30.
      The coefficients of variation for S2 and T30 were 15 % and 10 % respectively.
      CONCLUSIONS: Dark adaptation is slowed in normal ageing. CRT-based dark
      adaptometry is easily implemented and highly repeatable. The technique described
      in this article would be useful for documenting visual changes in future clinical
      trials assessing retinal health in the older eye with and without ocular
      pathology.

PMID- 23553289
TI  - Computational design of S-nitrosothiol "click" reactions.
AB  - To address a long-standing problem of finding efficient reactions for chemical
      labeling of protein-based S-nitrosothiols (RSNOs), we computationally explored
      hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes.
      Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20
      kcal/mol at the CBS-QB3 level) and compete with alternative S-N bond insertion
      pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically
      lowered by coordination of a Lewis acid to the N atom of the -SNO group. To
      exploit this effect, we propose to use reagents with Lewis acid and a strain
      activated carbon-carbon multiple bond linked by a rigid scaffold, which can react
      with RSNOs with small activation enthalpies (~5 kcal/mol) and high reaction
      exothermicities (~40 kcal/mol). The proposed efficient RSNO cycloaddition
      reactions can be used for future development of practical RSNO labeling
      reactions.

PMID- 23553288
TI  - Topical tacrolimus for the management of acute allergic conjunctivitis in a mouse
      model.
AB  - BACKGROUND: Acute allergic conjunctivitis is a constantly challenging condition
      that often requires steroids for effective management. Alternative treatment
      options are needed due to the potential side effects of steroids. Tacrolimus has
      been used for vernal/atopic conjunctivitis. The aim of our study was to
      investigate the therapeutic effect of topical administration of 0.03 % tacrolimus
      (eye drops or ointment) in comparison to 0.1 % dexamethasone in a mouse model of
      acute allergic conjunctivitis. METHODS: BALB/c mice were sensitized by an
      intraperitoneal injection of 10 MUg/0.2 ml ovalbumin (OVA) absorbed on ALUM (2.0
      mg) on days 1 and 8. They were challenged by topical instillation of 2 MUl of 15
      % OVA (absorbed in 10 % glycerol) twice daily, on days 15-21. Treatment was
      administered twice daily on days 17-21. Mice were randomly assigned topical
      treatment groups: Group 1, 0.1 % dexamethasone drops; Group 2, 0.03 % tacrolimus
      drops; Group 3, 0.03 % tacrolimus ointment; Group 4 PBS drops (control). On day
      22 all mice underwent clinical evaluation, blood sampling for IgE levels, and
      conjunctivas were removed for eosinophil counting. RESULTS: IgE and OVA-specific
      IgE levels were similar among all groups, demonstrating induction of allergic
      reaction in all mice. Significantly lower clinical scores were found among all
      treated groups as compared to controls (P < 0.001), while no significant
      difference was found among the three treatment groups (P > 0.05). Conjunctival
      eosinophil counts were significantly lower in Group 1 (P < 0.05) as compared to
      the other groups. CONCLUSIONS: The clinical efficacy of topical 0.03 % tacrolimus
      was similar to 0.1 % dexamethasone for acute allergic conjunctivitis.

PMID- 23553290
TI  - Transoral robotic surgery for treatment of obstructive sleep apnea-hypopnea
      syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of base of tongue (BOT) resection
      via transoral robotic surgery (TORS) in the treatment of obstructive sleep
      apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: Case series METHODS: Between June
      2010 and May 2012, BOT resection via TORS was performed on 27 patients with
      OSAHS. Patients were excluded from this analysis if other concomitant upper
      airway procedures such as uvulopalatopharyngoplasty were performed, or if
      postoperative polysomnograms were not available. RESULTS: Twelve patients who
      underwent BOT resection alone were included in this study. The median age for
      these 12 patients was 48.5 (range, 19-64) and included nine females and three
      males. The mean apnea-hypopnea index (AHI) was 43.9 +/- 41.1 preoperatively and
      17.6 +/- 16.2 postoperatively. This difference in AHI was statistically
      significant (P = 0.007) and reflected an average AHI reduction of 56.2 +/- 28.3%.
      Statistical significant reductions in daytime somnolence level, as measured by
      Epworth Sleepiness Scale (13.7 +/- 5.2 preoperatively vs. 6.4 +/- 4.5
      postoperatively, P <0.001), and snoring intensity, as reported by a bed partner
      using a Visual Analogue Scale (8.6 +/- 1.2 preoperatively vs. 4.2 +/- 1.9
      postoperatively, P <0.001), were achieved. There was no statistical significant
      difference between the preoperative and postoperative body mass index (34.5 +/-
      7.3 vs. 33.5 +/- 6.7, P = 0.296) or minimum oxygen saturation (83.3 +/- 5.5% vs.
      84.0 +/- 6.4%, P = 0.680). CONCLUSIONS: This is the first study looking at the
      use of TORS to address obstruction at the level of BOT only, not confounded by
      surgical alterations at other levels of upper airway. This preliminary result on
      the use of BOT resection via TORS for the treatment of patients with OSAHS is
      encouraging and warrants further investigations.

PMID- 23553291
TI  - Vertebral body stenting versus kyphoplasty for the treatment of osteoporotic
      vertebral compression fractures: a randomized trial.
AB  - BACKGROUND: In the treatment of vertebral compression fractures, vertebral body
      stenting with an expandable scaffold inserted before application of the bone
      cement was developed to impede secondary loss of vertebral height encountered in
      patients treated with balloon kyphoplasty. The purpose of this study was to
      clarify whether there are relevant differences between balloon kyphoplasty and
      vertebral body stenting with regard to perioperative and postoperative findings.
      METHODS: In a two-armed randomized controlled trial, patients with a total of 100
      fresh osteoporotic vertebral compression fractures were treated with either
      balloon kyphoplasty or vertebral body stenting. The primary outcome was the post
      interventional change in the kyphotic angle on radiographs. The secondary
      outcomes were the maximum pressure of the balloon tamp during inflation,
      radiation exposure time, perioperative complications, and cement leakage.
      RESULTS: The mean reduction (and standard deviation) of kyphosis (the kyphotic
      correction angle) was 4.5 degrees  +/- 3.6 degrees  after balloon kyphoplasty and
      4.7 degrees  +/- 4.2 degrees  after vertebral body stenting (p = 0.972). The mean
      pressures were 24 +/- 5 bar (348 +/- 72 pounds per square inch [psi]) during
      vertebral body stenting and 16 +/- 6 bar (233 +/- 81 psi) during balloon
      kyphoplasty (p = 0.014). There were no significant differences in radiation
      exposure time.None of the patients underwent revision surgery, and postoperative
      neurologic sequelae were not observed. Cement leakage occurred at twenty-five of
      the 100 vertebral levels without significant differences between the two
      intervention arms (p = 0.230). Intraoperative material-related complications were
      observed at one of the fifty vertebral levels in the balloon kyphoplasty group
      and at nine of the fifty levels in the vertebral body stenting group.
      CONCLUSIONS: No beneficial effect of vertebral body stenting over balloon
      kyphoplasty was found among patients with painful osteoporotic vertebral
      fractures with regard to kyphotic correction, cement leakage, radiation exposure
      time, or neurologic sequelae. Vertebral body stenting was associated with
      significantly higher pressures during balloon inflation and more material-related
      complications.

PMID- 23553292
TI  - The modified Dunn procedure for unstable slipped capital femoral epiphysis: a
      multicenter perspective.
AB  - BACKGROUND: The modified Dunn procedure has rapidly gained popularity as a
      treatment for unstable slipped capital femoral epiphysis (SCFE), but limited data
      exist regarding its safety and efficacy. The purpose of this study was to present
      results and complications following this procedure in a large multicenter series.
      METHODS: We reviewed the outcomes of all patients who had been treated with the
      modified Dunn procedure by five surgeons from separate tertiary-care
      institutions. All slipped capital femoral epiphyses were defined as unstable
      according to the Loder criteria. Patients with less than one year of follow-up
      and those with an underlying endocrinopathy or syndrome were excluded. All
      surgical procedures were performed by pediatric orthopaedic surgeons who had
      specific training in the modified Dunn procedure. Operative reports, outpatient
      records, and follow-up radiographs were used to determine the demographic
      information, type of fixation, final slip angle, presence of osteonecrosis, and
      any additional complications. Standardized surveys were administered to determine
      the pain level (0 to 10 scale), satisfaction (0 to 100 scale), function (modified
      Harris hip score, 0 to 91 scale), and activity level (UCLA [University of
      California Los Angeles] activity score, 0 to 10 scale) at time of the most recent
      follow-up. RESULTS: Twenty-seven patients (twenty-seven hips) with a mean of 22.3
      months (range, twelve to forty-eight months) of follow-up met the inclusion
      criteria. Four patients (15%) had broken implants at three to eighteen weeks
      after surgery and required revision fixation. Seven patients (26%) developed
      osteonecrosis at a mean of 21.4 weeks (range, ten to thirty-nine weeks), with
      each surgeon having at least one case of osteonecrosis. The mean slip angle at
      the time of the most recent follow-up was 6 degrees  (95% confidence interval, 2
      degrees  to 11 degrees ). Patients who did not develop osteonecrosis had
      significantly better clinical results compared with those who developed
      osteonecrosis, as demonstrated by a lower mean pain score (0.3 compared with 3.1,
      p = 0.002), higher level of satisfaction (97.1 compared with 65.8, p = 0.001),
      higher modified Harris hip score (88.0 compared with 60.0, p = 0.001), and higher
      UCLA activity score (9.3 compared with 5.9, p = 0.031). CONCLUSIONS: This largest
      reported series of unstable slipped capital femoral epiphyses treated with the
      modified Dunn procedure demonstrated that the procedure is capable of restoring
      anatomy and preserving function after a slip but that implant complications and
      osteonecrosis can and do occur postoperatively.

PMID- 23553293
TI  - Surgical treatment of chronic exertional compartment syndrome of the leg: failure
      rates and postoperative disability in an active patient population.
AB  - BACKGROUND: Chronic exertional compartment syndrome of the leg is a frequent
      source of lower-extremity pain in military personnel, competitive athletes, and
      runners. We are not aware of any previous study in which the authors rigorously
      evaluated the rates of return to full activity, persistent disability, and
      surgical revision after operative management of chronic exertional compartment
      syndrome of the leg in a large, physically active population. METHODS:
      Individuals who had undergone surgical fasciotomy of the anterior, lateral,
      and/or posterior compartments (current procedural terminology [CPT] codes 27600,
      27601, and 27602) for nontraumatic compartment syndrome of the lower extremity
      (International Classification of Diseases, Ninth Revision [ICD-9] code 729.72)
      between 2003 and 2010 were identified from the Military Health System Management
      Analysis and Reporting Tool (M2). Demographic variables including age, sex, and
      rank were extracted, and rates of postoperative complications, activity
      limitations, and revision surgery or medical discharge were obtained from the
      electronic medical record and U.S. Army Physical Disability Agency database.
      RESULTS: A total of 611 patients underwent 754 surgical procedures. The average
      patient age was 28.0 years, and 91.8% of the patients were male. Of the surgical
      procedures, 77.4% involved only anterior and lateral compartment releases; 19.4%
      addressed the anterior, lateral, and posterior compartments; and 2.2% addressed
      the posterior compartments alone. Symptom recurrence was reported by 44.7% of the
      patients, and 27.7% were unable to return to full activity. Surgical
      complications were documented for 15.7% of the patients, 5.9% underwent surgical
      revision, and 17.3% were referred for medical discharge because of chronic
      exertional compartment syndrome. Univariate analysis of prognostic factors
      revealed that surgical failure was associated with bilateral involvement (odds
      ratio [OR], 1.64), perioperative complications (OR, 2.12), activity limitations
      (OR, 4.41), and persistence of preoperative symptoms (OR, 8.46). Multivariable
      analysis confirmed significant associations between surgical failure and
      perioperative complications (OR, 1.72), activity limitations (OR, 2.23), and
      persistence of preoperative symptoms (OR, 5.47), whereas other factors were not
      significantly associated with surgical failure. CONCLUSIONS: Chronic exertional
      compartment syndrome is a substantial contributor to lower-extremity disability
      in the military population. Nearly half of all service members undergoing
      fasciotomy reported persistent symptoms, and one in five individuals had
      unsuccessful surgical treatment.

PMID- 23553294
TI  - The mechanism of action of induced membranes in bone repair.
AB  - BACKGROUND: Inducement of foreign-body granulation tissue is a relatively novel
      therapeutic modality in bone repair. A two-stage bone reconstruction method,
      known as the Masquelet technique, combines inducement of a granulation tissue
      membrane and subsequent bone autografting as a biphasic technique allowing
      reconstruction of large bone defects. In light of their already well
      characterized osteogenesis-improving capabilities in animals, we performed this
      translational study to investigate these membranes in patients. METHODS: Fourteen
      patients with complicated fractures and bone defects were randomly selected for
      this study. Biopsy samples of foreign-body-induced membranes were collected at
      different time points during scheduled surgical procedures. The membranes were co
      cultured with mesenchymal stromal cells, and differentiation into the
      osteoblastic lineage was assessed by measuring alkaline phosphatase activity,
      aminoterminal propeptide of type-I procollagen (PINP) production, and Ca2+
      concentration. Histological characteristics were evaluated with image analysis.
      Quantitative reverse transcription polymerase chain reaction was used to measure
      vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and type-I
      collagen (Col-1) expression. RESULTS: The induced membranes were characterized
      histologically by maturating vascularized fibrous tissue. The vascularization was
      greatest in one-month-old samples and decreased to <60% in three-month-old
      samples. One-month-old membrane samples had the highest expression of VEGF, IL-6,
      and Col-1, whereas two-month-old membranes expressed <40% of the levels of the
      one-month-old membranes. Specific alkaline phosphatase activity, PINP production,
      and Ca2+ concentration were increased in co-cultures when a membrane sample was
      present. In cultures of one-month-old membranes, PINP production was more than
      two times and Ca2+ deposition was four times higher than that in cultures of two
      month-old membranes. CONCLUSIONS: The induced membranes have osteogenesis
      improving capabilities. These capabilities, however, appear to decrease over
      time. We speculate that the optimal time for performing second-stage surgery may
      be within a month after implantation of foreign material.

PMID- 23553295
TI  - Treatment of advanced stages of hallux rigidus with cheilectomy and phalangeal
      osteotomy.
AB  - BACKGROUND: Surgical treatment of hallux rigidus has usually consisted of
      cheilectomy for mild to moderate disease and arthrodesis for more advanced
      disease. The reported failure rate for cheilectomy alone in patients with
      advanced disease is approximately 37.5%. We reported our results with the
      combination of cheilectomy and extension osteotomy at the proximal phalanx for
      the treatment of advanced hallux rigidus. METHODS: Between 2000 and 2007, eighty
      one patients with advanced hallux rigidus (classified as Hattrup and Johnson
      Grade III) underwent a unilateral cheilectomy and great toe proximal phalangeal
      extension osteotomy. Outcome assessment was determined by comparison of
      preoperative and postoperative American Orthopaedic Foot & Ankle Society scores,
      radiographs, first metatarsophalangeal joint motion, and patient satisfaction.
      Sixty-four of the eighty-one patients had complete clinical and radiographic
      examinations at a minimum duration of follow-up of two years. RESULTS: The mean
      duration of follow-up was 4.3 years. The mean dorsiflexion of the first
      metatarsophalangeal joint improved significantly (p < 0.05), by 27.0 degrees ,
      from 32.7 degrees  preoperatively to 59.7 degrees  postoperatively. The average
      American Orthopaedic Foot & Ankle Society scores improved significantly (p <
      0.05) from 67.2 points preoperatively to 88.7 points postoperatively. Radiographs
      of the interphalangeal joint made postoperatively showed no evidence of
      development of interphalangeal joint arthritis. Of the eighty-one patients, sixty
      nine (85.2%) were satisfied with the results of treatment and four (4.9%)
      subsequently underwent arthrodesis to treat persistent symptoms at the first
      metatarsophalangeal joint. CONCLUSIONS: To our knowledge, this study is the first
      to support the use of a combination of cheilectomy and extension osteotomy of the
      great toe proximal phalanx as an alternative to first metatarsophalangeal joint
      arthrodesis to manage patients with advanced hallux rigidus.

PMID- 23553296
TI  - Axonal loss in murine peripheral nerves following exposure to recombinant human
      bone morphogenetic protein-2 in an absorbable collagen sponge.
AB  - BACKGROUND: With the proven efficacy of recombinant human bone morphogenetic
      protein-2 (rhBMP-2) to treat open tibial fractures and promote spine fusion,
      there has been an increase in its off-label use. Recent studies have shown that
      BMPs play a role in nerve development and regeneration. Little is known about
      changes that result when rhBMP-2 is used in the vicinity of peripheral nerves.
      The purpose of this study is to characterize changes in peripheral nerves
      following exposure to rhBMP-2-soaked collagen sponges. METHODS: rhBMP-2 on an
      absorbable collagen sponge (ACS) was implanted directly on the sciatic nerves of
      Wistar rats. One and three weeks following surgery, the nerves were harvested and
      histological analysis was performed to evaluate inflammatory and structural
      changes. RESULTS: rhBMP-2-soaked collagen sponges induced ectopic bone formation
      in muscle tissue in all animals after three weeks, but did not cause bone
      formation within the nerve. Axonal swelling and splitting of the myelin sheath
      were observed in both experimental and control nerves and may be a result of
      surgical manipulation. The overall incidence of axonal loss was 15.8% in the
      rhBMP-2/ACS-exposed nerves and was 0% in control nerves (p < 0.05). CONCLUSIONS:
      rhBMP-2-soaked collagen sponges may adversely affect the axons of peripheral
      nerves by causing axonal dropout and loss of axons. Ectopic bone formation occurs
      within muscle tissues and not within the peripheral nerve. The axonal dropout may
      be a direct effect of rhBMP-2-soaked collagen sponges and not nerve compression
      as it was observed prior to ectopic bone formation.

PMID- 23553297
TI  - A novel patellofemoral scoring system for patellofemoral joint status.
AB  - BACKGROUND: We were not aware of a well-validated patellofemoral joint-specific
      scoring system. We performed this study to develop and validate a scoring system
      (Samsung Medical Center [SMC] patellofemoral scoring system) suitable for the
      evaluation of patellofemoral joint status. METHODS: We recruited 179 individuals
      consisting of a study group of 123 patients with anterior knee pain but without
      pain in another part of the knee, twenty-eight patients with knee pain other than
      anterior knee pain (group A), and twenty-eight healthy volunteers without knee
      pain (group B). Items in the development of the scoring system that showed a
      significant difference between the study group and group A and between the study
      group and the group B were selected. Test-retest reliability was measured by
      intraclass correlation coefficient, internal consistency was measured by the
      Cronbach alpha, content validity was assessed by ceiling and floor effects, and
      construct validity was determined by the association of the Feller scores and the
      SMC patellofemoral scores. RESULTS: After the item verification process,
      seventeen items (eight items for patellofemoral pain and nine items for
      patellofemoral function) were selected. Test-retest reliability for overall SMC
      patellofemoral scores showed excellent reliability (intraclass correlation
      coefficient, 0.85), and internal consistency was excellent (Cronbach alpha,
      0.97). Floor and ceiling effects were acceptable (<30%) for all the items of the
      SMC patellofemoral scoring system, except one: sitting down on a chair, in the
      patellofemoral function score. The SMC patellofemoral scores showed moderate
      correlation with the Feller scores (rho = -0.45). CONCLUSIONS AND CLINICAL
      RELEVANCE: The SMC patellofemoral score is a novel scoring system that
      distinguishes patients with anterior knee pain or patellofemoral dysfunction from
      patients with knee pain or dysfunction arising from other knee problems, and from
      those without knee pain. The reliability and validity of the SMC patellofemoral
      scoring system were verified in the present study.

PMID- 23553298
TI  - Clinical and radiographic outcomes of failed repairs of large or massive rotator
      cuff tears: minimum ten-year follow-up.
AB  - INTRODUCTION: Little information exists regarding the long-term outcome after
      structural failure of rotator cuff repair. We previously reported clinical
      improvement, despite a 94% rate of failure of healing, at two years of follow-up
      in a cohort of eighteen patients who had undergone arthroscopic repair of massive
      rotator cuff tears. The purpose of the present study was to evaluate the ten-year
      results for these patients with known structural failures of rotator cuff
      repairs. METHODS: Fifteen (83%) of eighteen patients were available for follow-up
      at ten years. Patients were evaluated with use of the American shoulder and elbow
      surgeons (ASES) score, the simple shoulder test (SST), a visual analog scale pain
      score, and the constant score. Radiographs and sonograms were assessed. RESULTS:
      The average age was 74.6 years at the time of the latest follow-up. The average
      ASES score was 79.4 points (range, 50 to 95 points) and the average visual analog
      scale pain score was 2.2 points (range, 1 to 4 points); both scores were
      unchanged from those at two years. The average SST score was 9.2 points (range, 6
      to 12 points), and the average age-adjusted Constant score was 73.2 points
      (range, 58.7 to 89.7 points). Of the patients with structurally failed repairs,
      all but one had radiographic signs of proximal humeral migration or cuff tear
      arthropathy: three had Hamada grade-2 changes, five had grade-3 changes, and
      three had Grade-4 changes (with two having grade-4a changes and one having grade
      4b changes). Ultrasound confirmed the persistence of all tears that had been seen
      at two years. CONCLUSIONS: Clinical improvements and pain relief after
      arthroscopic rotator cuff repair of large and massive tears are durable at the
      time of long-term (ten-year) follow-up, despite early structural failure of
      repair. Shoulders had a high rate of progression of radiographic signs associated
      with large rotator cuff tears. These results demonstrate that healing of large
      rotator cuff tears is not critical for long-term satisfactory clinical results in
      older patients.

PMID- 23553299
TI  - Premenopausal women with a distal radial fracture have deteriorated trabecular
      bone density and morphology compared with controls without a fracture.
AB  - BACKGROUND: Measurement of bone mineral density by dual x-ray absorptiometry
      combined with clinical risk factors is currently the gold standard in diagnosing
      osteoporosis. Advanced imaging has shown that older patients with fragility
      fractures have poor bone microarchitecture, often independent of low bone mineral
      density. We hypothesized that premenopausal women with a fracture of the distal
      end of the radius have similar bone mineral density but altered bone
      microarchitecture compared with control subjects without a fracture. METHODS:
      Forty premenopausal women with a recent distal radial fracture were prospectively
      recruited and matched with eighty control subjects without a fracture. Primary
      outcome variables included trabecular and cortical microarchitecture at the
      distal end of the radius and tibia by high-resolution peripheral quantitative
      computed tomography. Bone mineral density at the wrist, hip, and lumbar spine was
      also measured by dual x-ray absorptiometry. RESULTS: The fracture and control
      groups did not differ with regard to age, race, or body mass index. Bone mineral
      density was similar at the femoral neck, lumbar spine, and distal one-third of
      the radius, but tended to be lower in the fracture group at the hip and
      ultradistal part of the radius (p = 0.06). Trabecular microarchitecture was
      deteriorated in the fracture group compared with the control group at both the
      distal end of the radius and distal end of the tibia. At the distal end of the
      radius, the fracture group had lower total density and lower trabecular density,
      number, and thickness compared with the control group (-6% to -14%; p < 0.05 for
      all). At the distal end of the tibia, total density, trabecular density,
      trabecular thickness, and cortical thickness were lower in the fracture group
      than in the control group (-7% to -14%; p < 0.01). Conditional logistic
      regression showed that trabecular density, thickness, separation, and
      distribution of trabecular separation remained significantly associated with
      fracture after adjustment for age and ultradistal radial bone mineral density
      (adjusted odds ratios [OR]: 2.01 to 2.98; p < 0.05). At the tibia, total density,
      trabecular density, thickness, cortical area, and cortical thickness remained
      significantly associated with fracture after adjustment for age and femoral neck
      bone mineral density (adjusted OR:1.62 to 2.40; p < 0.05). CONCLUSIONS: Despite
      similar bone mineral density values by dual x-ray absorptiometry, premenopausal
      women with a distal radial fracture have significantly poorer bone
      microarchitecture at the distal end of the radius and tibia compared with control
      subjects without a fracture. Early identification of women with poor bone health
      offers opportunities for interventions aimed at preventing further deterioration
      and reducing fracture risk.

PMID- 23553300
TI  - Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint
      infection.
AB  - BACKGROUND: Differentiation between septic and aseptic loosening of joint
      replacements is essential for successful revision surgery, but reliable markers
      for the diagnosis of low-grade infection are lacking. The present study was
      performed to assess intra-articular and systemic levels of antimicrobial peptides
      and proinflammatory cytokines as diagnostic markers for periprosthetic joint
      infection. METHODS: Fifteen consecutive patients with staphylococcal
      periprosthetic joint infections and twenty control patients with aseptic
      loosening of total hip and knee replacements were included in this prospective,
      single-center, controlled clinical trial. Expression of the antimicrobial
      peptides human beta-defensin-2 (HBD-2), human beta-defensin-3 (HBD-3), and
      cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent
      assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in
      serum and joint aspirates with use of cytometric bead arrays. C-reactive protein
      in serum, microbiology, and histopathology of periprosthetic tissue served as the
      "gold standard" for the diagnosis of infection. RESULTS: The antimicrobial
      peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from
      patients with periprosthetic joint infection compared with patients with aseptic
      loosening, and the area under the curve (AUC) in a receiver operating
      characteristic curve analysis was equal to 0.745 and 0.875, respectively.
      Additionally, significant local increases in the proinflammatory cytokines
      interleukin (IL)-1beta, IL-4, IL-6, IL-17A, interferon (IFN)-gamma, and tumor
      necrosis factor (TNF)-alpha were observed to be associated with infection.
      Logistic regression analysis indicated that the combination of an antimicrobial
      peptide with another synovial fluid biomarker improved diagnostic accuracy; the
      AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3
      and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial
      peptides and cytokines in serum that showed a significant systemic increase in
      association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC
      value of <0.75). CONCLUSIONS: The present study showed promising results for the
      use of antimicrobial peptides and other biomarkers in synovial fluid for the
      diagnosis of periprosthetic joint infection, and analysis of the levels in
      synovial fluid was more accurate than analysis of serum.

PMID- 23553301
TI  - Complications following tension-band fixation of patellar fractures with
      cannulated screws compared with Kirschner wires.
AB  - BACKGROUND: Displaced patellar fractures are commonly stabilized with a modified
      anterior tension-band construct. The goal of the current study was to compare the
      incidence of complications after tension-band fixation of the patella with
      Kirschner wires as compared with cannulated screws. METHODS: We performed a
      retrospective cohort study of consecutive, surgically treated patellar fractures.
      Patients were divided into two cohorts: fractures fixed with use of Kirschner
      wires and fractures fixed with use of cannulated screws. The primary outcome
      measure was early loss of fixation that necessitated revision surgery. Secondary
      outcomes included early postoperative infection and the need for implant removal.
      RESULTS: Four hundred and forty-eight patellar fractures were studied. Kirschner
      wires were used for fixation in 315 (70%), and cannulated screws were used for
      fixation in 133 (30%). The incidence of fixation failure was 3.5% in the
      Kirschner-wire group and 7.5% in the screw group (p = 0.065). A postoperative
      infection occurred in 4.4% of patients in the Kirschner-wire group and 1.5% of
      patients in the screw group (p = 0.17). One hundred sixteen (37%) patients in the
      Kirschner-wire group and 30 (23%) in the screw group underwent elective implant
      removal (p = 0.003). After adjusting for confounding variables, a trend toward
      increased incidence of fixation failure with screws as compared with Kirschner
      wires was present (p = 0.083). Patients treated with Kirschner wires were twice
      as likely to undergo implant removal compared with those treated with screws (p =
      0.002). CONCLUSIONS: Serious complications are uncommon following treatment of
      patellar fractures with a modified tension-band technique, with use of either
      Kirschner wires or cannulated screws. In both groups the rate of fixation failure
      was low, as was the rate of postoperative infection. Symptomatic implants, the
      most common complication observed, were twice as frequent in patients treated
      with Kirschner wires.

PMID- 23553302
TI  - Anterior cruciate ligament injury-prevention programs.

PMID- 23553303
TI  - Intensive care unit versus hospital floor: a comparative study of postoperative
      management of patients with adolescent idiopathic scoliosis.
AB  - BACKGROUND: Patients undergoing posterior spinal instrumentation and fusion
      surgery for adolescent idiopathic scoliosis were admitted to the intensive care
      unit until two years ago, at which time we changed our protocol to admit these
      patients to the general hospital floor following a brief stay in a postanesthesia
      care unit. This study compared postoperative management on a hospital floor with
      that in the intensive care unit for patients with adolescent idiopathic scoliosis
      undergoing posterior spinal fusion. METHODS: A retrospective review of 124
      consecutive patients with adolescent idiopathic scoliosis treated with spinal
      fusion from August 2007 to August 2010 was performed. Inclusion criteria were a
      diagnosis of adolescent idiopathic scoliosis and posterior spinal instrumentation
      and fusion surgery. RESULTS: Of 124 patients, sixty-six were managed
      postoperatively in the intensive care unit and fifty-eight, on the hospital
      floor. The mean age at the time of surgery was fourteen years. A mean of eleven
      vertebral levels (range, six to fifteen levels) were fused. No significant
      difference between the groups was found with respect to the mean age at the time
      of surgery, mean weight, mean preoperative and postoperative Cobb angles, and
      mean number of levels fused (p >= 0.12). However, the use of analgesic and
      antianxiety medication, number of postoperative blood tests, days of hospital
      stay, and number of physical therapy sessions were significantly decreased in the
      floor group compared with the intensive care unit group (p <= 0.05). No patient
      from the floor group had to be admitted to the intensive care unit. The mean
      charge was $33,121 for the floor group and $39,252 for the intensive care unit
      group (p < 0.001). CONCLUSIONS: Initial postoperative management of patients with
      adolescent idiopathic scoliosis following a posterior spinal instrumentation and
      fusion surgery on a general hospital floor, rather than in an intensive care
      unit, was associated with a shorter hospital stay, fewer blood tests, less
      analgesic and antianxiety medication usage, and fewer physical therapy sessions
      at this high-volume, academic, tertiary-care children's hospital. In addition to
      improved patient outcomes, there was a significant decrease of 16% in hospital
      charges for the group that did not go to the intensive care unit.

PMID- 23553304
TI  - Local vitamin-C injection reduced tendon adhesion in a chicken model of flexor
      digitorum profundus tendon injury.
AB  - BACKGROUND: Adhesion formation is a complication of hand flexor tendon repair.
      Normal gliding function of flexor tendons can be impaired by an excessive
      fibrotic response, which may be caused by intraoperative and postoperative
      hemorrhage. As tissue damage and hemorrhage can disturb redox regulation, thereby
      favoring fibrotic responses, the purpose of this study was to investigate if
      antioxidants can reduce tendon adhesion by antagonizing oxidative stress.
      METHODS: Flexor digitorum profundus tendon injury was induced in fifty-seven
      chickens. In twelve chickens, oxidative stress preinjury, immediately after
      injury, and two and six weeks postinjury (n = 3 at each time period) was
      estimated by measuring tissue levels of the reduced form of glutathione (GSH) and
      oxidized glutathione (glutathione disulfide [GSSG]) in the proximal
      interphalangeal joint. In the remaining chickens, 50 MUL of saline solution or
      vitamin-C solution (5 or 50 mg/mL) was injected into the wound immediately after
      closure of the tendon sheath. Samples were harvested at two weeks (n = 6 in each
      group) or six weeks (n = 6 in each group) postinjury for a gliding test,
      ultrasound imaging, and histological examination. Three chickens from each group
      were killed at two weeks postinjury for GSH and GSSG measurements to evaluate the
      treatment effects on postoperative oxidative stress. RESULTS: The GSH level was
      significantly decreased at two and six weeks postinjury, and the GSSG level was
      significantly increased at six weeks postinjury. Both 5 and 50-mg/mL vitamin C
      led to higher tissue levels of GSH at two weeks postinjury, as compared with that
      in the saline solution group, but no significant change in the GSSG level was
      detected. Chickens with vitamin-C supplementation showed no significant
      improvement in gliding resistance and no significant reduction of the fibrotic
      size at two weeks postinjury, but they did show significant improvement in
      gliding resistance at six weeks postinjury and the 5-mg/mL vitamin-C group showed
      a significant reduction of the fibrotic size at six weeks. Histological
      examination showed less peritendinous adhesion in the vitamin-C groups.
      CONCLUSIONS: Our results suggest that local injection of vitamin-C solution can
      reduce the extent of adhesion of healing tendons, probably by redox modulation,
      in a chicken model.

PMID- 23553305
TI  - Fractures in children: epidemiology and activity-specific fracture rates.
AB  - BACKGROUND: Approximately one-third of pediatric fractures occur during sport or
      recreational activity. In this paper, we investigate the incidence and causes of
      pediatric fractures in our region and quantify the fracture rate per exposure
      time for the most common sport and recreational activities. METHODS: We
      prospectively evaluated all children younger than sixteen years who presented to
      our institution with a new fracture within a twelve-month period. Exposure time
      to the most common childhood activities was measured by means of interviewing
      random parents from the study population. The main outcome measures were the
      annual fracture incidence in the population and fracture rates per 10,000 hours
      of exposure to various sports and recreational activities. RESULTS: A total of
      1403 fractures were included. The overall annual incidence was 180.1 fractures
      per 10,000 children younger than sixteen years. The distal part of the radius was
      most often fractured (436 fractures, 31.1%). Snowboarding was associated with the
      highest activity-specific fracture rate, estimated to be 1.9 (95% confidence
      interval [CI], 1.16 to 2.60) fractures per 10,000 hours of exposure. In
      comparison, the fracture rate per 10,000 hours of exposure was 0.79 (CI, 0.42 to
      1.09) for handball, 0.44 (CI, 0.35 to 0.52) for soccer, and 0.35 (CI, 0.23 to
      0.47) for trampolining. CONCLUSIONS: The distal part of the radius is the most
      common fracture site in childhood. Fracture rates differ between various physical
      activities. The fracture rate for snowboarding was four times higher compared
      with that for other common childhood sport and recreational activities in our
      region.

PMID- 23553306
TI  - Hemophilic arthropathy of shoulder joints: clinical, radiographic, and
      ultrasonographic characteristics of seventy patients.
AB  - BACKGROUND: Although shoulder problems frequently occur in patients with
      hemophilia, systematic evaluation of shoulder joint damage in these patients has
      only rarely been reported. METHODS: The clinical, radiographic, and
      ultrasonographic characteristics of the shoulder joint were studied in a cohort
      of seventy consecutive patients with hemophilia. We collected information on age,
      disease severity, history of shoulder hemarthrosis, prophylaxis therapy,
      functional Oxford shoulder score, and crutch use. Both shoulders of each patient
      were evaluated with shoulder motion and visual analog pain scale scores as well
      as with radiography and ultrasonography. RESULTS: Sixty-six patients had
      hemophilia A, and four had hemophilia B. The median age was thirty-four years
      (range, ten to sixty-three years). Fifty-six shoulders in thirty-five patients
      had shoulder bleeds, and twenty-seven patients (38.6%) had shoulder pain or
      limited motion. As determined with radiographs, eighteen (25.7%) of the seventy
      patients had hemophilic shoulder arthropathy. A strong correlation between the
      functional Oxford shoulder score and the radiographic Pettersson score was also
      noted (r = 0.749, p < 0.001). The ultrasonographic abnormalities in the fifty-six
      hemarthrotic shoulders included chondromalacia (76.8%), osseous irregularity
      (60.7%), bicipital tenosynovitis (60%), partial-thickness rotator cuff tear
      (35.7%), and full-thickness rotator cuff tear (17.9%). Older age, the absence of
      any previous prophylaxis therapy, and higher frequency of crutch use were the
      most significant factors associated with shoulder bleeds. CONCLUSIONS: Shoulder
      arthropathy is relatively common in patients with hemophilia. Rotator cuff tears
      were common in the present study, and there was a strong correlation between
      shoulder function and the radiographic severity of the arthropathy.
      Ultrasonography was useful for the evaluation of disorders of the soft tissues of
      the hemophilic shoulder.

PMID- 23553307
TI  - Authorship proliferation in the orthopaedic literature.
AB  - BACKGROUND: Authorship is the currency of the academic orthopaedic surgeon. There
      has been an unprecedented increase in the number of authors per publication in
      many biomedical fields. Possible reasons for this trend include increased
      complexity of research, "undeserved" authorship, and the "pressure to publish."
      We explored the change in authorship in two leading orthopaedic journals over a
      period of sixty years. METHODS: We examined all original research articles and
      case reports published in The Journal of Bone and Joint Surgery (American and
      British Volumes) (JBJS-A and JBJS-B) in ten-year intervals from 1949 to 2009. For
      each article, we determined the number of authors, the geographic origin of the
      research, and the academic degrees of the authors; we also examined the changes
      that occurred in these categories. RESULTS: The mean number of authors per
      original research article increased from 1.6 in 1949 to 5.1 in 2009. There has
      been a noticeable internationalization of the two journals, with a decreasing
      proportion of articles from North America and the United Kingdom and Ireland as a
      result of increased contributions from Europe and the Far East. Authors with
      advanced research degrees (PhD; MS; MD, PhD; and MD, MS) account for an
      increasing proportion of contributing authors; over 30% of authors had an
      advanced research degree in 2009. CONCLUSIONS: Our findings suggest that the
      trend of authorship proliferation in biomedical research is also seen in the
      orthopaedic literature. The mean number of authors, the proportion of authors per
      research article with an advanced research degree, and variation in the
      geographic origin of articles has increased over the past sixty years.

PMID- 23553308
TI  - What is the relationship between number of publications during orthopaedic
      residency and selection of an academic career?
AB  - BACKGROUND: Although many residents partake in academic pursuits, including the
      publication of clinical studies, laboratory research, case reports, and review
      articles, it is uncertain whether such experiences are associated with a career
      long interest in an academic orthopaedic career. METHODS: This single-institution
      study was conducted with use of data from an urban academic university-based
      residency program. An academic career was defined as attainment of a teaching
      title signifying inclusion in, or affiliation with, a teaching department.
      Additionally, an academic career was subclassified as either full academic or
      semi-academic on the basis of employment characteristics. A PubMed search was
      conducted for publications by all 130 orthopaedic surgery residents who began
      their training in our residency program during the 1987-1988 through 2003-2004
      academic years. An analysis was performed to determine whether the number or type
      of publications during residency or demographic variables were associated with
      selection of an academic career on completion of training. RESULTS: The mean
      total number of publications during residency was greater for individuals who
      chose an academic career (4.8) than for those who chose a nonacademic career
      (2.4). When the year of residency graduation was considered, a greater number of
      publications during residency correlated with a more recent year of graduation in
      residents who selected an academic position. There were no differences with
      regard to sex, possession of advanced degrees, or completion of an additional
      research year between individuals who selected an academic compared with a
      nonacademic career. CONCLUSIONS: Graduates of our orthopaedic residency program
      who pursued an academic career were likely to have published more articles during
      residency compared with their nonacademic peers.

PMID- 23553309
TI  - Vertebral body stenting: establishing the value of a novel percutaneous cement
      augmenting technique for the treatment of vertebral body compression fractures:
      Commentary on an article by Clement M.L. Werner, MD, et al.: "Vertebral body
      stenting versus kyphoplasty for the treatment of osteoporotic vertebral
      compression fractures. A randomized trial".

PMID- 23553310
TI  - It's not as easy as it looks: Commentary on an article by Wudbhav N. Sankar, MD,
      et al.: "The modified Dunn procedure for unstable slipped capital femoral
      epiphysis. a multicenter perspective".

PMID- 23553311
TI  - Chronic exertional compartment syndrome: are surgical outcomes worse in soldiers
      compared with civilians?: Commentary on an article by CPT Brian R. Waterman, MD,
      et al.: "Surgical treatment of chronic exertional compartment syndrome of the
      leg: failure rates and postoperative disability in an active patient population".

PMID- 23553312
TI  - Failure to rescue patients after reintervention in gastroesophageal cancer
      surgery in England.
AB  - IMPORTANCE: Gastroesophageal cancer resections are associated with significant
      reintervention and perioperative mortality rates. OBJECTIVE: To compare outcomes
      following operative and nonoperative reinterventions between high- and low
      mortality gastroesophageal cancer surgical units in England. DESIGN: All elective
      esophageal and gastric resections for cancer between 2000 and 2010 in English
      public hospitals were identified from a national administrative database. Units
      were divided into low- and high-mortality units (LMUs and HMUs, respectively)
      using a threshold of 5% or less for 30-day adjusted mortality. The groups were
      compared for reoperations and nonoperative reinterventions following
      complications. SETTING: Both LMUs and HMUs. PARTICIPANTS: Patients who underwent
      esophageal and gastric resections for cancer. EXPOSURE: Elective esophageal and
      gastric resections for cancer, with reoperations and nonoperative reinterventions
      following complications. MAIN OUTCOMES AND MEASURES: Failure to rescue is defined
      as the death of a patient following a complication; failure to rescue-surgical is
      defined as the death of a patient following reoperation for a surgical
      complication. RESULTS: There were 14 955 esophagectomies and 10 671 gastrectomies
      performed in 141 units. For gastroesophageal resections combined, adjusted
      mortality rates were 3.0% and 8.3% (P < .001) for LMUs and HMUs, respectively.
      Complications rates preceding reoperation were similar (5.4% for LMUs vs. 4.9%
      for HMUs; P = .11). The failure to rescue-surgical rates were lower in LMUs than
      in HMUs (15.3% vs. 24.1%; P < .001). The LMUs performed more nonoperative
      reinterventions than the HMUs did (6.7% vs. 4.7%; P < .001), with more patients
      surviving in LMUs than in HMUs (failure to rescue rate, 7.0% vs. 12.5%; P <
      .001). Overall, LMUs reintervened more than HMUs did (12.2% vs 9.6%; P < .001),
      and LMUs had lower failure to rescue rates following reintervention than HMUs did
      (9.0% vs. 18.3%; P = .001). All P values stated refer to 2-sided values.
      CONCLUSIONS AND RELEVANCE: Overall, LMUs were more likely to reintervene and
      rescue patients following gastroesophageal cancer resections in England. Patients
      were more likely to survive following both reoperations and nonsurgical
      interventions in LMUs.

PMID- 23553313
TI  - Such as pigs eat: the rise and fall of the pannage pig in the UK.
AB  - Mast-feeding systems once formed the mainstay of pork production across Europe,
      but have now largely been forgotten. One of the earliest farming practices, it
      allowed people to fatten pigs on an otherwise wasted resource. Mast feeding was
      vital in the ancient world: Rome, Saxon England and the Normans all relied
      heavily on woodland pigs. As time and technology advanced, mast systems became
      outmoded and fell into disuse. However, recent public interest in improved animal
      welfare and sustainable agriculture, combined with anecdotal reports of improved
      flavour, has once again brought mast feeding into the spotlight. This article
      chronicles the changes in popularity and perception of mast-feeding systems
      throughout history, and uses the historical perspective to outline a possible
      future for woodland pigs.

PMID- 23553315
TI  - Emerging sulfated flavonoids and other polyphenols as drugs: nature as an
      inspiration.
AB  - Nature uses sulfation of endogenous and exogenous molecules mainly to avoid
      potential toxicity. The growing importance of natural sulfated molecules, as
      modulators of a number of physiological and pathological processes, has inspired
      the synthesis of non-natural sulfated scaffolds. Until the 1990s, the synthesis
      of sulfated small molecules was almost restricted to derivatives of flavonoids
      and aimed mainly at structure elucidation and plant biosynthesis studies.
      Currently, the synthesis of this type of compounds concerns structurally diverse
      scaffolds and is aimed at the development of potential drugs and/or exploitation
      of the biological effects of sulfated metabolites. Some important hit compounds
      are emerging from sulfated flavonoids and other polyphenols mainly as
      anticoagulant and antiviral agents. When compared with polymeric macromolecules
      such as heparins, sulfated small molecules could be of value in therapeutics due
      to their hydrophobic nature that can contribute to improve the bioavailability.
      This review highlights the synthetic approaches that were applied to obtain
      monosulfated or polysulfated phenolic small molecules and compiles the diverse
      biological activities already reported for this type of derivatives. Toxicity and
      pharmacokinetic parameters of this emerging class of derivatives will also be
      considered, emphasizing their value for therapeutic applications. 

PMID- 23553314
TI  - Neurochemical changes in the rat occipital cortex and hippocampus after
      repetitive and profound hypoglycemia during the neonatal period: an ex vivo 1H
      magnetic resonance spectroscopy study.
AB  - The brain of a human neonate is more vulnerable to hypoglycemia than that of
      pediatric and adult patients. Repetitive and profound hypoglycemia during the
      neonatal period (RPHN) causes brain damage and leads to severe neurologic
      sequelae. Ex vivo high-resolution (1)H nuclear magnetic resonance (NMR)
      spectroscopy was carried out in the present study to detect metabolite
      alterations in newborn and adolescent rats and investigate the effects of RPHN on
      their occipital cortex and hippocampus. Results showed that RPHN induces
      significant changes in a number of cerebral metabolites, and such changes are
      region-specific. Among the 16 metabolites detected by ex vivo (1)H NMR, RPHN
      significantly increased the levels of creatine, glutamate, glutamine, gamma
      aminobutyric acid, and aspartate, as well as other metabolites, including
      succine, taurine, and myo-inositol, in the occipital cortex of neonatal rats
      compared with the control. By contrast, changes in these neurochemicals were not
      significant in the hippocampus of neonatal rats. When the rats had developed into
      adolescence, the changes above were maintained and the levels of other
      metabolites, including lactate, N-acetyl aspartate, alanine, choline, glycine,
      acetate, and ascorbate, increased in the occipital cortex. By contrast, most of
      these metabolites were reduced in the hippocampus. These metabolic changes
      suggest that complementary mechanisms exist between these two brain areas. RPHN
      appears to affect occipital cortex and hippocampal activities, neurotransmitter
      transition, energy metabolism, and other metabolic equilibria in newborn rats;
      these effects are further aggravated when the newborn rats develop into
      adolescence. Changes in the metabolism of neurotransmitter system may be an
      adaptive measure of the central nervous system in response to RPHN.

PMID- 23553316
TI  - Monitoring the source monitoring.
AB  - The hypothesis that the retrieval of correct source memory cues, those leading to
      a correct source attribution, increases confidence, whereas the retrieval of
      incorrect source memory cues, those leading to a source misattribution, decreases
      confidence was tested. Four predictions were derived from this hypothesis: (1)
      confidence should be higher for correct than incorrect source attribution except;
      (2) when no source cues are retrieved; (3) only the source misattributions
      inferred from the retrieval of incorrect source cues will be rated with low
      confidence; and (4) the number of source cues retrieved, either correct or
      incorrect, will affect the confidence in the source attributions. To test these
      predictions, participants read two narratives from two witnesses to a bank
      robbery, a customer and a teller. Then, participants completed a source
      monitoring test with four alternatives, customer, teller, both, or neither, and
      rated their confidence in their source attribution. Results supported the first
      three predictions, but they also suggested that the number of correct source
      monitoring cues retrieved did not play a role in the monitoring of the accuracy
      of the source attributions. Attributions made from the recovery of incorrect
      source cues could be tagged as dubious or uncertain, thus leading to lowered
      confidence irrespective of the number of incorrect source cues or whether another
      correct source cue was also recovered. This research has potential applications
      for eyewitness memory because it shows that confidence can be an indicator of the
      accuracy of a source attribution. 

PMID- 23553317
TI  - Enhanced mental rotation ability in time-space synesthesia.
AB  - Time-space synesthesia is a variant of sequence-space synesthesia and involves
      the involuntary association of months of the year with 2D and 3D spatial forms,
      such as arcs, circles, and ellipses. Previous studies have revealed conflicting
      results regarding the association between time-space synesthesia and enhanced
      spatial processing ability. Here, we tested 15 time-space synesthetes, and 15 non
      synesthetic controls matched for age, education, and gender on standard tests of
      mental rotation ability, spatial working memory, and verbal working memory.
      Synesthetes performed better than controls on our test of mental rotation, but
      similarly to controls on tests of spatial and verbal working memory. Results
      support a dissociation between visuo-spatial imagery and spatial working memory
      capacity, and suggest time-space synesthesia is associated only with enhanced
      visuo-spatial imagery. These data are consistent with the time-space connectivity
      thesis that time-space synesthesia results from enhanced connectivity in the
      parietal lobe between regions supporting the representation of temporal sequences
      and those underlying visuo-spatial imagery. 

PMID- 23553319
TI  - Munch's Self-portrait Between Clock and Bed.

PMID- 23553321
TI  - Pharmacologic treatment of hypertension in patients with chronic kidney disease.
AB  - Hypertension remains an important cause of morbidity and mortality in patients
      with chronic kidney disease. It both contributes to and is a consequence of
      chronic renal dysfunction. There is a high prevalence of hypertension in chronic
      kidney disease, and rates of control remain sub-optimal. Numerous studies have
      highlighted the benefit of treating hypertension in reducing the overall
      mortality as well as progression of renal disease in this population. Non
      pharmacologic treatment strategies remain the primary intervention in all
      patients but are insufficient on their own to control hypertension in most cases.
      Pharmacologic treatment recommendations, however, vary depending on the specific
      etiology of disease as well as patient characteristics. Though most classes of
      anti-hypertensive drugs can be used to lower blood pressure in chronic kidney
      disease, therapy needs to be selected based on the presence of specific co
      morbidities as well as the etiology of the kidney disease. Most patients will
      require multi-drug therapy for achieving target blood pressure goals. This review
      discusses the pharmacologic options in management of hypertension in various
      forms of chronic kidney disease.

PMID- 23553322
TI  - Molecular characterization of coat protein gene of Garlic common latent virus
      isolates from India: an evidence for distinct phylogeny and recombination.
AB  - The coat protein (CP) gene of five Indian Garlic common latent virus (GarCLV)
      isolates was sequenced and it was 960 bp long in all the five isolates, encoding
      a protein of 319 amino acids. Comparative nucleotide sequence analysis revealed
      diversity of 4.3% among the Indian isolates and of 11.9% among all isolates
      worldwide. Amino acid sequence comparison showed a significant variability in the
      N-terminal of CP of GarCLV. Various protein analysis tools identified thirteen
      conserved domains and motifs including Carlavirus and Potexvirus-specific Flexi
      CP and Flexi N CP. Phylogenetic analysis clustered GarCLV isolates in the
      subgroup II with isolates from Australia, Brazil, Japan, and South Korea.
      Intraspecies recombination study revealed that only one of the Indian isolates
      was a recombinant. Interspecies recombination study suggested the absence of
      genetic exchange from Carlavirus species to GarCLV; conversely, GarCLV was
      identified as a putative donor for at least two other Carlavirus species. This is
      the first report of molecular variability and recombination in GarCLV isolates.

PMID- 23553323
TI  - Transoral robotic assisted nasopharyngectomy via a lateral palatal flap approach.

PMID- 23553324
TI  - Efficacy of "hammock" tympanoplasty in the treatment of anterior perforations.
AB  - OBJECTIVES/HYPOTHESIS: Surgical repair of large anterior tympanic membrane (TM)
      perforations continue to be a challenge for the otologic surgeon. Lateral graft
      tympanoplasty, the recommended treatment, is technically difficult and is plagued
      with blunting of the anterior sulcus and lateralization of the TM, both of which
      can lead to conductive hearing loss. In this study, we evaluate the efficacy of
      "hammock" tympanoplasty in the treatment of anterior perforation. STUDY
      DESIGN/METHODS: The "hammock" tympanoplasty, a medial graft tympanoplasty,
      utilizes a large tympanomeatal flap incorporating anterior ear canal skin and the
      placement of a graft extending from the anterior to the posterior external
      auditory canal, akin to a hammock. In this retrospective study, the medical,
      surgical, audiological, and radiological records of 25 patients treated with
      hammock tympanoplasty were reviewed. RESULTS: The average age of the patients was
      40.6 +/- 20 years. The perforation involved the right ear of 17 patients, and at
      least two quadrants of the TM in 24 of 25 patients. The TM perforation was
      successfully closed in 24 of 25 patients, with improvement of the air conduction
      threshold in 22 of 25 patients. None of the patients experienced SNHL or
      lateralization of TM. There was one patient with blunting of anterior sulcus and
      another patient who experienced delayed facial paresis 9 days following surgery,
      which subsequently resolved. CONCLUSION: The hammock tympanoplasty is technically
      easy, highly effective in restoring the integrity of the TM, and shows
      improvement in postoperative hearing. LEVEL OF EVIDENCE: 4.

PMID- 23553325
TI  - Low body mass index and jaw movement are protective of hearing in users of
      personal listening devices.
AB  - OBJECTIVES/HYPOTHESIS: Sound pressure level delivered through personal listening
      devices (PLDs) and reaching the ear drum might be affected by body size and jaw
      movements. This study aimed to investigate whether jaw movement and/or smaller
      body mass index (BMI) resulted in decrease of sound pressure level within the ear
      canals of PLD users via an earbud earphone. STUDY DESIGN: Case series. METHODS:
      Forty-five normal-hearing subjects (16 males; mean age, 23.3 years) participated
      in this study. A probe-microphone system was used to measure sound pressure level
      in the external ear canal with music delivered from a media player via an earbud
      earphone. Test materials consisted of two 20-second excerpts from a heavy metal
      music piece. Subjects were instructed to adjust the volume of the media player to
      conform to three conditions for sound pressure measurement: comfortable, loud,
      and maximum. Measurements were then repeated while subjects mimicked chewing
      action under the same listening conditions. RESULTS: Sound pressure levels were
      significantly lower when measured with jaw movement than without jaw movement (P
      < .05). Sound pressure levels monitored with/without jaw movement were generally
      lower in subjects with a BMI<23 than those with a BMI >= 23 (P < .05).
      CONCLUSIONS: Jaw movement and low BMI (<23) reduced the overall sound level of
      PLDs at the ear canal. Sound pressure levels detected in the external ear canal
      of our subjects using earbud earphones were significantly lower under conditions
      of jaw movement/BMI <23. Our research invites further studies on a larger group
      of PLD users to correlate these variables with hearing threshold shifts over
      time.

PMID- 23553326
TI  - Accommodating missingness when assessing surrogacy via principal stratification.
AB  - BACKGROUND: When an outcome of interest in a clinical trial is late-occurring or
      difficult to obtain, surrogate markers can extract information about the effect
      of the treatment on the outcome of interest. Understanding associations between
      the causal effect (CE) of treatment on the outcome and the causal effect of
      treatment on the surrogate is critical to understanding the value of a surrogate
      from a clinical perspective. PURPOSE: Traditional regression approaches to
      determine the proportion of the treatment effect explained by surrogate markers
      suffer from several shortcomings: they can be unstable and can lie outside the 0
      1 range. Furthermore, they do not account for the fact that surrogate measures
      are obtained post randomization, and thus, the surrogate-outcome relationship may
      be subject to unmeasured confounding. METHODS: to avoid these problems are of key
      importance. Methods Frangakis and Rubin suggested assessing the CE within
      prerandomization 'principal strata' defined by the counterfactual joint
      distribution of the surrogate marker under the different treatment arms, with the
      proportion of the overall outcome CE attributable to subjects for whom the
      treatment affects the proposed surrogate as the key measure of interest. Li et
      al. developed this 'principal surrogacy' approach for dichotomous markers and
      outcomes, utilizing Bayesian methods that accommodated nonidentifiability in the
      model parameters. Because the surrogate marker is typically observed early,
      outcome data are often missing. Here, we extend Li et al. to accommodate missing
      data in the observable final outcome under ignorable and nonignorable settings.
      We also allow for the possibility that missingness has a counterfactual
      component, a feature that previous literature has not addressed. RESULTS: We
      apply the proposed methods to a trial of glaucoma control comparing surgery
      versus medication, where intraocular pressure (IOP) control at 12 months is a
      surrogate for IOP control at 96 months. We also conduct a series of simulations
      to consider the impacts of nonignorability, as well as sensitivity to priors and
      the ability of the decision information criterion (DIC) to choose the correct
      model when parameters are not fully identified. LIMITATIONS: Because model
      parameters cannot be fully identified from data, informative priors can introduce
      nontrivial bias in moderate sample size settings, while more noninformative
      priors can yield wide credible intervals. CONCLUSIONS: Assessing the linkage
      between CEs of treatment on a surrogate marker and CEs of a treatment on an
      outcome is important to understanding the value of a marker. These CEs are not
      fully identifiable; hence, we explore the sensitivity and identifiability aspects
      of these models and show that relatively weak assumptions can still yield
      meaningful results.

PMID- 23553328
TI  - Correlative study of functional and structural regeneration of urothelium after
      chitosan-induced injury.
AB  - High transepithelial electrical resistance (TEER) demonstrates a functional
      permeability barrier of the normal urothelium, which is maintained by a layer of
      highly differentiated superficial cells. When the barrier is challenged, a quick
      regeneration is induced. We used side-by-side diffusion chambers as an ex vivo
      system to determine the time course of functional and structural urothelial
      regeneration after chitosan-induced injury. The exposure of the urothelium to
      chitosan caused a 60 % decrease in TEER, the exposure of undifferentiated
      urothelial cells to the luminal surface and leaky tight junctions. During the
      regeneration period (350 min), TEER recovered to control values after
      approximately 200 min, while structural regeneration continued until 350 min
      after injury. The tight junctions are the earliest and predominant component of
      the barrier to appear, while complete barrier regeneration is achieved by delayed
      superficial cell terminal differentiation. The barrier function and the structure
      of untreated urothelium were unaffected in side-by-side diffusion chambers for at
      least 6 h. The urinary bladder tissue excised from an animal thus retains the
      ability to maintain and restore the transepithelial barrier and cellular
      ultrastructure for a sufficient period to allow for studies of regeneration in ex
      vivo conditions.

PMID- 23553327
TI  - Expectations for weight loss and willingness to accept risk among patients
      seeking weight loss surgery.
AB  - IMPORTANCE: Weight loss surgery (WLS) has been shown to produce long-term weight
      loss but is not risk free or universally effective. The weight loss expectations
      and willingness to undergo perioperative risk among patients seeking WLS remain
      unknown. OBJECTIVES: To examine the expectations and motivations of WLS patients
      and the mortality risks they are willing to undertake and to explore the
      demographic characteristics, clinical factors, and patient perceptions associated
      with high weight loss expectations and willingness to assume high surgical risk.
      DESIGN: We interviewed patients seeking WLS and conducted multivariable analyses
      to examine the characteristics associated with high weight loss expectations and
      the acceptance of mortality risks of 10% or higher. SETTING: Two WLS centers in
      Boston. PARTICIPANTS: Six hundred fifty-four patients. MAIN OUTCOME MEASURES:
      Disappointment with a sustained weight loss of 20% and willingness to accept a
      mortality risk of 10% or higher with WLS. RESULTS: On average, patients expected
      to lose as much as 38% of their weight after WLS and expressed disappointment if
      they did not lose at least 26%. Most patients (84.8%) accepted some risk of dying
      to undergo WLS, but only 57.5% were willing to undergo a hypothetical treatment
      that produced a 20% weight loss. The mean acceptable mortality risk to undergo
      WLS was 6.7%, but the median risk was only 0.1%; 19.5% of all patients were
      willing to accept a risk of at least 10%. Women were more likely than men to be
      disappointed with a 20% weight loss but were less likely to accept high mortality
      risk. After initial adjustment, white patients appeared more likely than African
      American patients to have high weight loss expectations and to be willing to
      accept high risk. Patients with lower quality-of-life scores and those who
      perceived needing to lose more than 10% and 20% of weight to achieve "any" health
      benefits were more likely to have unrealistic weight loss expectations. Low
      quality-of-life scores were also associated with willingness to accept high risk.
      CONCLUSIONS AND RELEVANCE: Most patients seeking WLS have high weight loss
      expectations and believe they need to lose substantial weight to derive any
      health benefits. Educational efforts may be necessary to align expectations with
      clinical reality.

PMID- 23553329
TI  - Proximal dominant hereditary motor and sensory neuropathy with proximal dominance
      association with mutation in the TRK-fused gene.
AB  - IMPORTANCE: Hereditary motor and sensory neuropathy with proximal dominance (HMSN
      P) has been reported as a rare type of autosomal dominant adult-onset Charcot
      Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since
      1997, and the causative gene has not been found. OBJECTIVES: To identify the
      genetic cause of HMSN-P in a Korean family and determine the pathogenic
      mechanism. DESIGN: Genetic and observational analysis. SETTING: Translational
      research center for rare neurologic disease. PARTICIPANTS: Twenty-eight
      individuals (12 men and 16 women) from a Korean family with HMSN-P. MAIN OUTCOME
      MEASURES: Whole-exome sequencing, linkage analysis, and magnetic resonance
      imaging. RESULTS: Through whole-exome sequencing, we revealed that HMSN-P is
      caused by a mutation in the TRK-fused gene (TFG). Clinical heterogeneities were
      revealed in HMSN-P between Korean and Japanese patients. The patients in the
      present report showed faster progression of the disease compared with the
      Japanese patients, and sensory nerve action potentials of the sural nerve were
      lost in the early stages of the disease. Moreover, tremor and hyperlipidemia were
      frequently found. Magnetic resonance imaging of the lower extremity revealed a
      distinct proximal dominant and sequential pattern of muscular involvement with a
      clearly different pattern than patients with Charcot-Marie-Tooth disease type 1A.
      Particularly, endoneural blood vessels revealed marked narrowing of the lumen
      with swollen vesicular endothelial cells. CONCLUSIONS AND RELEVANCE: The
      underlying cause of HMSN-P proves to be a mutation in TFG that lies on chromosome
      3q13.2. This disease is not limited to Japanese descendants, and marked narrowing
      of endoneural blood vessels was noted in the present study. We believe that TFG
      can affect the peripheral nerve tissue.

PMID- 23553330
TI  - Investigating the influence of haemodynamic stimuli on intracranial aneurysm
      inception.
AB  - We propose a novel method to reconstruct the hypothetical geometry of the healthy
      vasculature prior to intracranial aneurysm (IA) formation: a Frenet frame is
      calculated along the skeletonization of the arterial geometry; upstream and
      downstream boundaries of the aneurysmal segment are expressed in terms of the
      local Frenet frame basis vectors; the hypothetical healthy geometry is then
      reconstructed by propagating a closed curve along the skeleton using the local
      Frenet frames so that the upstream boundary is smoothly morphed into the
      downstream boundary. This methodology takes into account the tortuosity of the
      arterial vasculature and requires minimal user subjectivity. The method is
      applied to 22 clinical cases depicting IAs. Computational fluid dynamic
      simulations of the vasculature without IA are performed and the haemodynamic
      stimuli in the location of IA formation are examined. We observe that locally
      elevated wall shear stress (WSS) and gradient oscillatory number (GON) are highly
      correlated (20/22 for WSS and 19/22 for GON) with regions susceptible to sidewall
      IA formation whilst haemodynamic indices associated with the oscillation of the
      WSS vectors have much lower correlations.

PMID- 23553331
TI  - On the vibrational linear and nonlinear optical properties of compounds involving
      noble gas atoms: HXeOXeH, HXeOXeF, and FXeOXeF.
AB  - The vibrational (hyper)polarizabilities of some selected Xe derivatives are
      studied in the context of Bishop-Kirtman perturbation theory (BKPT) and numerical
      finite field methodology. It was found that for this set of rare gas compounds,
      the static vibrational properties are quite large, in comparison to the
      corresponding electronic ones, especially those of the second
      hyperpolarizability. This also holds for the dc-Pockels beta(-omega;omega,0),
      Kerr gamma(-omega;omega,0,0) and electric field second harmonic generation gamma
      (-2omega;omega,omega,0) effects, although the computed nuclear relaxation (nr)
      vibrational contributions are smaller in magnitude than the static ones. HXeOXeH
      was used to study the effects of electron correlation, basis set, and geometry.
      Geometry effects were found to lead to noticeable changes of the vibrational and
      electronic second hyperpolarizability. A limited study of the effect of Xe
      insertion to the nr vibrational properties is also reported. Assessment of the
      results revealed that Xe insertion has a remarkable effect on the nr
      (hyper)polarizabilities. In terms of the BKPT, this is associated with a
      remarkable increase of the electrical and mechanical anharmonicity terms. The
      latter is consistent with the anharmonic character of several vibrational modes
      reported for rare gas compounds.

PMID- 23553332
TI  - High-performance liquid chromatographic enantioseparation of (RS)-bupropion using
      isothiocyanate-based chiral derivatizing reagents.
AB  - A high-performance liquid chromatographic (HPLC) method for enantioseparation of
      bupropion was developed using two isothiocyanate-based chiral derivatizing
      reagents, (S)-1-(1-naphthyl) ethyl isothiocyanate, (S)-NEIT, and (R)-alpha-methyl
      benzyl isothiocyanate, (R)-MBIT. The diastereomers synthesized with (S)-NEIT were
      enantioseparated by reversed-phase HPLC using gradient elution with mobile phase
      containing water and acetonitrile, whereas diastereomers synthesized with (R)
      MBIT were enantioseparated using triethyl amine phosphate buffer and methanol.
      Derivatization conditions were optimized and the method was validated for
      accuracy, precision and limit of detection. The limit of detection was found to
      be 0.040-0.043 ug/mL for each of the diastereomers prepared with (S)-NEIT.

PMID- 23553333
TI  - Identification of novel biomarkers in neuroblastoma associated with the risk for
      bone marrow metastasis: a pilot study.
AB  - PURPOSE: Neuroblastoma is a common pediatric neoplasm with variable
      histopathological features that carry an inherent risk of developing distant
      metastases, in particular bone marrow metastasis. Nestin, X-linked inhibitor of
      apoptosis (XIAP) and vascular growth factors (VEGF) are biomarkers that are
      implicated in the tumorigenesis of various cancers. We studied the expression of
      these biomarkers in neuroblastoma, in relation to bone marrow (BM) metastasis and
      other histologic parameters. METHODS: Patients with neuroblastoma included seven
      with BM metastasis and 12 with non-metastatic tumors. Slides from the primary
      tumors were immunostained with antibodies against nestin, XIAP, VEGF-A, VEGF-B,
      VEGF-D, VEGF-R1, and VEGF-R2. Immunostaining results were evaluated by two
      pathologists, graded and statistically correlated with the risk of developing BM
      metastasis. RESULTS: Nestin was expressed in 16/19 cases with no significant
      difference between patients with BM metastasis and those without BM metastasis.
      XIAP was identified in 18/19 tumor cases; the staining density was significantly
      lower in patients with bone marrow metastasis and those with unfavorable
      histology. VEGF-R1, VEGF-R2, and VEGF-B were expressed while VEGF-A and VEGF-D
      were not. Significantly, higher expression of VEGF-B was noted in patients with
      BM metastasis. CONCLUSION: Expression of VEGF-B and XIAP in neuroblastoma may
      play a role in the development of bone marrow metastasis. Given the limited
      number of patients in this study, a larger cohort is needed to validate these
      findings.

PMID- 23553334
TI  - Assessment of p38alpha in peripheral blood mononuclear cells (PBMC): a potential
      blood protein marker of head and neck squamous cell carcinoma.
AB  - PURPOSE: Solid tumors involve an inflammatory microenvironment portrayed by
      immune cells playing role in cancer progression via inflammatory p38alpha mitogen
      activated protein kinase (MAPK) molecule that produces pro-inflammatory cytokines
      TNFalpha, IL1beta and IL6. This study quantified and compared the expression of
      p38alpha in peripheral blood mononuclear cells (PBMCs) of HNSCC patients with the
      healthy subjects. METHODS: The PBMC were isolated from the 35 control and 83
      HNSCC patients. The expression of p38alpha in PBMCs was assessed using surface
      plasmon resonance (SPR), ELISA and western blot analysis. RESULTS: p38alpha
      levels were found to be over-expressed in HNSCC patients 0.98 ng/MUl (95 % CI
      0.95-1.02) as compared to controls 0.46 ng/MUl (95 % CI 0.42-0.50) (p < 0.0001).
      CONCLUSION: p38alpha is over-expressed in PBMCs of HNSCC patients and may play a
      role in the progression of cancer. This research may translate a protein marker
      for HNSCC to clinical oncologist for therapeutic intervention and use as a
      predictive marker.

PMID- 23553336
TI  - The challenges for global harmonisation of food safety norms and regulations:
      issues for India.
AB  - Safe and adequate food is a human right, safety being a prime quality attribute
      without which food is unfit for consumption. Food safety regulations are framed
      to exercise control over all types of food produced, processed and sold so that
      the customer is assured that the food consumed will not cause any harm. From the
      Indian perspective, global harmonisation of food regulations is needed to improve
      food and nutrition security, the food trade and delivery of safe ready-to-eat
      (RTE) foods at all places and at all times. The Millennium Development Goals
      (MDGs) put forward to transform developing societies incorporate many food safety
      issues. The success of the MDGs, including that of poverty reduction, will in
      part depend on an effective reduction of food-borne diseases, particularly among
      the vulnerable group, which includes women and children. Food- and water-borne
      illnesses can be a serious health hazard, being responsible for high incidences
      of morbidity and mortality across all age groups of people. Global harmonisation
      of food regulations would assist in facilitating food trade within and outside
      India through better compliance, ensuring the safety of RTE catered foods, as
      well as addressing issues related to the environment. At the same time,
      regulations need to be optimum, as overregulation may have undue negative effects
      on the food trade.

PMID- 23553337
TI  - Nitrogen-fixing bacteria with multiple plant growth-promoting activities enhance
      growth of tomato and red pepper.
AB  - As a suitable alternative to chemical fertilizers, the application of plant
      growth-promoting rhizobacteria has been increasing in recent years due to their
      potential to be used as biofertilizers. In the present work, 13 nitrogen-fixing
      bacterial strains belonging to 11 different genera were tested for their PGP
      attributes. All of the strains were positive for 1-aminocyclopropane-1
      carboxylate deaminase (ACCD), indole-3-acetic acid (IAA), salicylic acid, and
      ammonia production while negative for cellulase, pectinase, and hydrocyanic acid
      production. The strains Pseudomonas sp. RFNB3 and Serratia sp. RFNB14 were the
      most effective in solubilizing both tri-calcium phosphate and zinc oxide. In
      addition, all strains except Pseudomonas sp. RFNB3 were able to oxidize sulfur,
      and six strains were positive for siderophore synthesis. Each strain tested in
      this study possesses at least four PGP properties in addition to nitrogen
      fixation. Nine strains were selected based on their multiple PGP potential,
      particularly ACCD and IAA production, and evaluated for their effects on early
      growth of tomato and red pepper under gnotobiotic conditions. Bacterial
      inoculation considerably influenced root and shoot length, seedling vigor, and
      dry biomass of the two crop plants. Three strains that demonstrated substantial
      effects on plant performance were further selected for greenhouse trials with red
      pepper, and among them Pseudomonas sp. RFNB3 resulted in significantly higher
      plant height (26%) and dry biomass (28%) compared to control. The highest rate of
      nitrogen fixation, as determined by acetylene reduction assay, occurred in
      Novosphingobium sp. RFNB21 inoculated red pepper root (49.6 nM of ethylene/h/g of
      dry root) and rhizosphere soil (41.3 nM of ethylene/h/g of dry soil). Inoculation
      with nitrogen-fixing bacteria significantly increased chlorophyll content, and
      the uptake of different macro- and micro-nutrient contents enhancing also in red
      pepper shoots, in comparison with uninoculated controls. The population
      estimation studies showed that nitrogen-fixing as well as total heterotrophic
      bacteria were also noticeably increased in soil and plant samples. The findings
      of this study suggest that certain nitrogen-fixing strains possessing multiple
      PGP traits could be applied in the development of biofertilizers. 

PMID- 23553338
TI  - Morphological reconstruction of the neoepiglottis after hyo-sub-glosso
      epiglottectomy (anteriorly extended supraglottic laryngectomy).

PMID- 23553339
TI  - RNA interference in the treatment of colon cancer.
AB  - Colorectal cancer is the third most common cancer in both men and women and has
      shown a progressive increase over the past 20 years. Current chemotherapy has
      major limitations, and a novel therapeutic approach is required. Given that
      neoplastic transformation of colon epithelial cells is a consequence of genetic
      and epigenetic alterations, RNA interference (RNAi) has been proposed as a new
      therapeutic strategy that offers important advantages over conventional
      treatments, with high specificity and potency and low toxicity. RNAi has been
      employed as an effective tool to study the function of genes, preventing their
      expression and leading to the development of new approaches to cancer treatment.
      In malignancies, including colon cancer, RNAi is being used for "silencing" genes
      that are deregulated by different processes such as gene amplification, mutation,
      or overexpression and may be the cause of oncogenesis. This strategy not only
      provides information on the involvement of certain genes in colon cancer, but
      also opens up a new perspective for its treatment. However, most studies have
      used adenovirus or lentivirus vectors to transport RNAi into tumor cells or
      tumors in animal models, because several technical obstacles must be overcome
      before RNAi can be used in the clinical setting. The aim of this study was to
      review current knowledge on the use of RNAi techniques in the treatment of colon
      cancer.

PMID- 23553340
TI  - Development and regulation of biosimilars: current status and future challenges.
AB  - Biologic medicinal products developed via rDNA technology as recombinant protein
      based medicines that have been in clinical use since the early 1980s as original
      biopharmaceuticals have greatly contributed to the therapy of severe metabolic
      and degenerative diseases. The recent expiration of the data protection or
      patents for most of them created opportunities for the development of copy
      versions of original biopharmaceuticals with similar biologic activity (termed
      biosimilars). Production of these new products is expected to meet worldwide
      demand, promote market competition, maintain the incentives for innovation, and
      sustain the healthcare systems. The licencing of these products, however, relies
      on the experience gained with the original biopharmaceuticals. Critical issues
      related to this class of medicinal products include their terminology (to avoid
      confusion with generics and non-innovator copy versions that have not been tested
      according to the biosimilar guidelines), manufacturing, and regulation. The
      European Union (EU) has been the first to establish a regulatory framework for
      marketing authorization application (MAA) and has named these products
      biosimilars, a term also recently adopted by the US FDA. Unlike the conventional,
      more common small molecular weight human medicines and chemical generics, protein
      based medicines exhibit higher molecular weight, complexity in structure and
      function that can be affected by changes in the manufacturing process. Therefore,
      biosimilars represent a relatively heterogeneous class of medicinal products that
      make their regulation quite challenging. According to the current understanding
      in the EU, a biosimilar is a copy version of an already authorized
      biopharmaceutical (or reference product) with similar biologic activity,
      physicochemical characteristics, efficacy, and safety, based on a full
      comparability exercise at quality, preclinical and clinical level to ensure
      similar efficacy and safety. Guidance has been provided through several Committee
      for Medicinal Products for Human Use (CHMP) guidelines as well as individual
      scientific advice requested from the European Medicines Agency (EMA) by various
      companies for the development and regulation of biosimilars. This review is
      mainly focused on the current status of regulation of biosimilars in the EU as
      well as on future challenges lying ahead for the improvement of the requirements
      needed for the marketing authorization of biosimilars. Emphasis is given on the
      quality requirements concerning these medicinal products (biologics).

PMID- 23553341
TI  - Submucosal resection of the middle turbinate.

PMID- 23553342
TI  - The evolving role of antifungal susceptibility testing.
AB  - Although increasing numbers of hospital microbiology laboratories are performing
      antifungal susceptibility testing (AST), its routine use is uncommon. The utility
      of AST is founded on the belief that susceptibility (or resistance) of an agent
      allows some prediction of clinical outcome. This review provides an overview of
      the development of antifungal susceptibility testing methodology, including wild
      type minimum inhibitory concentration (MIC) distributions, epidemiologic
      breakpoints, and Interpretive Clinical Breakpoints for antifungal agents. In
      addition, we examine the current clinical utility of AST and the clinical data
      support utilized in the development of clinical breakpoints (CBP) for common
      pathogens causing invasive fungal infections. In the treatment of fungal
      infections, identifying consistent correlations between MICs - or susceptibility
      category - and clinical outcomes is an ongoing challenge, and current data sets
      are insufficient for many drugs and pathogens to enable the development,
      revision, or confirmation of CBPs. Antifungal susceptibility testing is of
      current value, but further research in many areas is needed before MICs are
      independently used to guide treatment decisions.

PMID- 23553343
TI  - Regenerative phonosurgical treatments for vocal fold scar and sulcus with basic
      fibroblast growth factor.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold scar and sulcus are still challenges. Basic
      fibroblast growth factor (bFGF) has proven to be effective to resolve scar tissue
      in animal models. This study reports the efficacy of regenerative treatments
      using bFGF on vocal fold scar and sulcus in human cases. STUDY DESIGN:
      Retrospective chart review. METHODS: Fifteen cases (7 scar; 8 sulcus) were
      treated by either local injection of bFGF (n = 6) or regenerative surgery using
      bFGF (n = 9). Injection regimen was to locally apply 10 micrograms of bFGF in 0.5
      mL saline into each vocal fold under topical anesthesia repeatedly (4 times with
      intervals of 1 week between each injection). The regenerative surgical procedure
      consisted of the dissection of scar tissue and the implant of gelatin sponge with
      bFGF. Follow-up periods ranged from 6 months to 24 months. RESULTS: Maximum
      Phonation Time (MPT); Voice Handicap Index (VHI)-10; and Grade, Roughness,
      Breathiness, Asthenia, Strain (GRBAS) scale were assessed in both groups. The
      injection group showed significant improvement on VHI-10 and GRBAS. The
      regenerative surgery group showed significant improvement in all parameters.
      Jitter and shimmer were evaluated in the surgery group, and the results indicated
      improvement in six and five cases of nine cases, respectively. No major adverse
      effects were observed in both treatment groups. CONCLUSIONS: Regenerative
      treatments using bFGF has shown to be effective for improvement of vocal function
      in scar and sulcus.

PMID- 23553344
TI  - Risk factors for beta-amyloid deposition in healthy aging: vascular and genetic
      effects.
AB  - IMPORTANCE: Identifying risk factors for increased beta-amyloid (Abeta)
      deposition is important for targeting individuals most at risk for developing
      Alzheimer disease and informing clinical practice concerning prevention and early
      detection. OBJECTIVE: To investigate risk factors for Abeta deposition in
      cognitively healthy middle-aged and older adults. Specifically, we hypothesized
      that individuals with a vascular risk factor such as hypertension, in combination
      with a genetic risk factor for Alzheimer disease (apolipoprotein E epsilon4
      allele), would show greater amyloid burden than those without such risk. DESIGN:
      Cross-sectional study. SETTING: General community. PARTICIPANTS: One hundred
      eighteen well-screened and cognitively normal adults, aged 47 to 89 years.
      Participants were classified in the hypertension group if they reported a medical
      diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm
      Hg diastolic, as measured across 7 occasions at the time of study. INTERVENTION:
      Participants underwent Abeta positron emission tomography imaging with
      radiotracer fluorine 18-labeled florbetapir. Participants were genotyped for
      apolipoprotein E and were classified as epsilon4(+) or epsilon4(-). MAIN OUTCOME
      MEASURE: Amyloid burden. RESULTS: Participants in the hypertension group with at
      least 1 epsilon4 allele showed significantly greater amyloid burden than those
      with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure
      was strongly associated with increased mean cortical amyloid level for subjects
      with at least 1 epsilon4 allele. CONCLUSIONS AND RELEVANCE: Vascular disease is a
      prevalent age-related condition that is highly responsive to both behavioral
      modification and medical treatment. Proper control and prevention of risk factors
      such as hypertension earlier in the life span may be one potential mechanism to
      ameliorate or delay neuropathological brain changes with aging.

PMID- 23553345
TI  - Aggregate versus day level association between methamphetamine use and HIV
      medication non-adherence among gay and bisexual men.
AB  - Methamphetamine use is associated with HIV infection, especially among gay and
      bisexual men. Methamphetamine use contributes to disease progression both
      directly, by increasing viral load and damaging the immune system, and
      indirectly, by decreasing medication adherence. Research examining the
      association of methamphetamine use and non-adherence has traditionally compared
      groups of users and nonusers on adherence, compared methamphetamine use between
      participants above or below some threshold level of adherence (e.g. >90 % dose
      adherence), or examined aggregate relationships. Using Timeline Follow-back
      procedures, the present study examined aggregate, threshold, and day-level
      associations of methamphetamine use with non-adherence in 210 HIV-positive gay
      and bisexual methamphetamine-using men. Methamphetamine use was not associated
      with adherence behavior at the aggregate-level, but methamphetamine use on a
      given day was associated with 2.3 times the odds of non-adherence on that day.
      Threshold results were equivocal. These data suggest that the methamphetamine and
      non-adherence relationship is complicated: non-adherence is more likely to occur
      on days in which methamphetamine is used, but participants reported more non
      adherence days in which methamphetamine was not used. This seeming paradox
      generates questions about the selection of analytical techniques and has
      important implications for behavioral interventions targeting substance use and
      adherence among HIV-positive individuals.

PMID- 23553346
TI  - Social support network characteristics and sexual risk taking among a
      racially/ethnically diverse sample of young, urban men who have sex with men.
AB  - Associations between social support network characteristics and sexual risk among
      racially/ethnically diverse young men who have sex with men (YMSM) were examined
      using egocentric network data from a prospective cohort study of YMSM (n = 501)
      recruited in New York City. Bivariate and multivariable logistic regression
      analyses examined associations between social support network characteristics and
      sexual risk taking behaviors in Black, Hispanic/Latino, and White YMSM. Bivariate
      analyses indicated key differences in network size, composition, communication
      frequency and average relationship duration by race/ethnicity. In multivariable
      analyses, controlling for individual level sociodemographic, psychosocial and
      relationship factors, having a sexual partner in one's social support network was
      associated with unprotected sexual behavior for both Hispanic/Latino (AOR = 3.90)
      and White YMSM (AOR = 4.93). Further examination of key network characteristics
      across racial/ethnic groups are warranted in order to better understand the
      extant mechanisms for provision of HIV prevention programming to
      racially/ethnically diverse YMSM at risk for HIV.

PMID- 23553347
TI  - Feasibility, acceptability and preliminary efficacy of an online peer-to-peer
      social support ART adherence intervention.
AB  - This study describes the results of an online social support intervention, called
      "Thrive with Me" (TWM), to improve antiretroviral therapy (ART) adherence. HIV
      positive gay or bisexually-identified men self-reporting imperfect ART adherence
      in the past month were randomized to receive usual care (n = 57) or the eight
      week TWM intervention (n = 67). Self-reported ART outcome measures (0-100 % in
      the past month) were collected at baseline, post-intervention, and 1-month follow
      up. Follow-up assessment completion rate was 90%. Participants rated (1-7 scale)
      the intervention high in information and system quality and overall satisfaction
      (Means >= 5.0). The intervention showed modest effects for the overall sample.
      However, among current drug-using participants, the TWM (vs. Control) group
      reported significantly higher overall ART adherence (90.1 vs. 57.5% at follow-up;
      difference = 31.1, p = 0.02) and ART taken correctly with food (81.6 vs. 55.7% at
      follow-up; difference = 47.9, p = 0.01). The TWM intervention appeared feasible
      to implement, acceptable to users, and demonstrated greatest benefits for current
      drug users.

PMID- 23553349
TI  - Pipek-Mezey localization of occupied and virtual orbitals.
AB  - Recent advances in orbital localization algorithms are used to minimize the Pipek
      Mezey localization function for both occupied and virtual Hartree-Fock orbitals.
      Virtual Pipek-Mezey orbitals for large molecular systems have previously not been
      considered in the literature. For this work, the Pipek-Mezey (PM) localization
      function is implemented for both the Mulliken and a Lowdin population analysis.
      The results show that the standard PM localization function (using either
      Mulliken or Lowdin population analyses) may yield local occupied orbitals,
      although for some systems the occupied orbitals are only semilocal as compared to
      state-of-the-art localized occupied orbitals. For the virtual orbitals, a Lowdin
      population analysis shows improvement in locality compared to a Mulliken
      population analysis, but for both Mulliken and Lowdin population analyses, the
      virtual orbitals are seen to be considerably less local compared to state-of-the
      art localized orbitals.

PMID- 23553348
TI  - Moderating effect of age on the association between alcohol use and sexual risk
      in MSM: evidence for elevated risk among younger MSM.
AB  - Men who have sex with men (MSM) are substantially impacted by HIV/AIDS in the
      United States. Alcohol use is frequently studied as a predictor of sexual risk in
      MSM, but findings for this association have been mixed. Developmental differences
      in this effect may help to explain equivocal findings. 143 MSM (analytic sample
      137) ages 16-40 completed weekly diaries of sexual encounters and associated
      situational factors for 12 weeks. Analyses were conducted with Hierarchical
      Linear Modeling. Alcohol use before sex was not associated with sexual risk
      across all participants. Participant age moderated this effect; alcohol use
      before sex was associated with increased odds of sexual risk in younger MSM only.
      These analyses expand on previous findings by utilizing a wider age range than
      most prior studies and adjusting for the effects of several theoretically
      selected covariates. Young MSM are an important group to target for addressing
      alcohol use in the context of sexual behavior.

PMID- 23553350
TI  - Validity and reliability reporting practices in the field of health education and
      behavior: a review of seven journals.
AB  - Health education and behavior researchers and practitioners often develop, adapt,
      or adopt surveys/scales to quantify and measure cognitive, behavioral, emotional,
      and psychosocial characteristics. To ensure the integrity of data collected from
      these scales, it is vital that psychometric properties (i.e., validity and
      reliability) be assessed. The purpose of this investigation was to (a) determine
      the frequency with which published articles appearing in health education and
      behavior journals report the psychometric properties of the scales/subscales
      employed and (b) outline the methods used to determine the reliability and
      validity of the scores produced. The results reported herein are based on a final
      sample of 967 published articles, spanning seven prominent health education and
      behavior journals between 2007 and 2010. Of the 967 articles examined, an
      exceedingly high percentage failed to report any validity (ranging from 40% to
      93%) or reliability (ranging from 35% to 80%) statistics in their articles. For
      health education/behavior practitioners and researchers to maximize the utility
      and applicability of their findings, they must evaluate the psychometric
      properties of the instrument employed, a practice that is currently
      underrepresented in the literature. By not ensuring the instruments employed in a
      given study were able to produce accurate and consistent scores, researchers
      cannot be certain they actually measured the behaviors and/or constructs
      reported. 

PMID- 23553351
TI  - A concise review of HPLC, LC-MS and LC-MS/MS methods for determination of
      azithromycin in various biological matrices.
AB  - Azithromycin is one of the best selling antibiotics in the world. It belongs to
      the new macrolide family of azalides. It is derived from erythromycin and it
      differs from erythromycin in having a 15-membered ring and a methyl substituted
      nitrogen inserted at the 9a position in the aglycone ring. This structural
      modification confers favourable microbiological and pharmacokinetic
      characteristics on azithromycin and greater acid stability compared with
      erythromycin. It is mainly used to treat respiratory infections, sexually
      transmitted diseases, cutaneous and soft-tissue infections, etc. This review
      provides a comprehensive overview of various HPLC, LC-MS and LC-MS/MS methods for
      quantitation of azithromycin in different biological matrices. In addition, it
      provides general information on extraction steps, internal standard selection,
      conditions for chromatographic separation, brief validation data and applicable
      conclusions for reported methods in a defined pattern.

PMID- 23553352
TI  - Video-assisted thoracoscopy as an important tool for trauma surgeons: a
      systematic review.
AB  - PURPOSE: Trauma patients frequently have serious chest injuries. Retained
      hemothoraces and persistent pneumothoraces are among the most frequent
      complications of chest injuries which may lead to major, long-term morbidity and
      mortality if these complications are not recognized and treated appropriately.
      Video-assisted thoracoscopy (VATS) is a well-established technique in surgical
      practice. The usefulness of VATS for treatment of complications after chest
      trauma has been demonstrated by several authors. However, there is an ongoing
      debate about the optimal timing of VATS. METHODS: A computerized search was
      conducted which yielded 450 studies reporting on the use of VATS for thoracic
      trauma. Eighteen of these studies were deemed relevant for this review. The
      quality of these studies was assessed using a check-list and the PRISMA
      guidelines. Outcome parameters were successful evacuation of the retained
      hemothorax or treatment of other complications as well as reduction of empyema
      rate, length of hospital stay, and hospital costs. RESULTS: There was only one
      randomized trial and two prospective studies. Most studies report case series of
      institutional experiences. VATS was found to be very successful in evacuation of
      retained hemothoraces and seems to reduce the empyema rate subsequently.
      Furthermore, the length of hospital stay and costs can be drastically reduced
      with the early use of VATS. CONCLUSION: Early VATS is an effective treatment for
      retained hemothoraces or other complications of chest trauma. We propose a
      clinical pathway, in which VATS is used as an early intervention in order to
      prevent serious complications such as empyemas or trapped lung.

PMID- 23553353
TI  - Increased costs of perioperative risk assessment for thyroid surgery in elderly
      people (over 80 years) presenting with benign disease.
AB  - BACKGROUND/OBJECTIVES: Evaluate how surgical treatment of benign thyroid disease
      in elderly people is prone to induce an increase of costs in the next future due
      to the aging process of the population. METHODS: A retrospective analysis has
      been performed on a total of 116 patients operated between January 2007 and
      September 2011, divided in a group of 58 patients aged over 80 years (Group A)
      and 58 patients younger than 80 years (Group B). The analyzed data included age,
      preoperative diagnosis, severe co-morbidities, procedures other than standard
      needed to evaluate anaesthesiological risk, postoperative hospital stay,
      complications, duration of postoperative intensive care monitoring, pathologic
      characteristics, and costs of anaesthesiological risk assessment. RESULTS:
      Statistical analysis of collected data showed that the costs related to
      perioperative risk assessment (p value < 0.001) and the duration of hospital stay
      (p value < 0.001) were higher in Group A than in Group B. Instead, surgery
      related complications were not statistically different. CONCLUSIONS: Despite
      feasibility and safety of modern surgical techniques, indications for surgery in
      elderly patients affected by benign thyroid disease should be reserved mainly for
      those patients with severe medical necessity.

PMID- 23553354
TI  - Enhanced biodiversity and pollination in UK agroforestry systems.
AB  - Monoculture farming systems have had serious environmental impacts such as loss
      of biodiversity and pollinator decline. The authors explain how temperate
      agroforestry systems show potential in being able to deliver multiple
      environmental benefits.

PMID- 23553355
TI  - Parental stress in raising Mandarin-speaking children with cochlear implants.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the characteristics of parental stress in
      the child, parent, and total domains in families of Mandarin-speaking children
      with cochlear implants at four different time periods in the implantation
      process. Previous studies have shown that parental stress lessens after cochlear
      implantation surgery. STUDY DESIGN: Cross-sectional case series. METHODS: Self
      reported questionnaires based on Abidin's Parenting Stress Index (Taiwanese
      edition) were filled out by 113 mothers of children with cochlear implants.
      Factors related to parental stress were analyzed. In addition, we calculated the
      percentage of families experiencing high levels of stress (percentile >= 90) and
      compared the differences in stress level between each time period
      (preoperatively, postoperative time < 2 years, postoperative time between 2 and 5
      years, and postoperative time >5 years). RESULTS: Parent socioeconomic status,
      patient sex, and patient age were significantly related to the total parental
      stress. In the study of families experiencing high-stress between each time
      period, we found that parents had the highest level of parenting stress during
      the period of 0 to 2 years postoperatively in the total (odds ratio, 1.89) and
      child domain (odds ratio, 4.23). The contrary result was found in the parent
      domain, of which the highest odds ratio was found in the preoperative period.
      CONCLUSIONS: Although parental stress in the parent domain lessened after the
      cochlear implantation surgery, parents experienced the highest level of total
      parental stress during the period of 0 to 2 years postoperatively. The degree of
      total parenting stress did not lessen after the cochlear implantation surgery.
      LEVEL OF EVIDENCE: 4.

PMID- 23553356
TI  - Studies on salinization in Haryana soils on free-living nitrogen-fixing bacterial
      populations and their activity.
AB  - A total of 26 soil samples from saline soils of Haryana were collected. Based on
      their electrical conductivity (EC) values, which varied from 1.04 to 21.00 dS m(
      1), the soils were categorized into non-saline soils (EC 0-2 dS m(-1)), weakly
      saline soils (EC 2-4 dS m(-1)), saline soils (EC 4-8 dS m(-1)), strongly saline
      soils (EC 8-16 dS m(-1)), and very strongly saline soils (EC >16 dS m(-1)). The
      pH values of these soil samples ranged from 6.03 to 8.62, while organic C, total
      N, and available P were in the range of 0.06-0.94%, 0.07-0.15%, and 0.11-0.29 MUg
      g(-1) soil, respectively. As a measure of the impact of salinity on free-living
      N(2) fixers and their activity, the total bacterial populations on four media
      (Jensen's nitrogen-free medium, malate medium, Burk's medium, and soil extract
      agar medium) decreased from 6.12 to 3.70 log CFU g(-1) soil with increasing
      salinity level. PCR amplification of the nifH region of the DNA from 234 selected
      morphotypes from all the media showed the presence of nifH in 71 isolates. Out of
      these, 37% of the isolates were obtained using Jensen's medium; 35, 28, and 21%
      of the isolates were obtained using soil extract medium, Burk's medium, and
      malate medium, respectively. The majority of the free-living N(2) fixers (67%)
      were Gram negative. Apart from the acetylene reduction assay (ARA) activity in
      these isolates, other beneficial traits like ammonia excretion and indole acetic
      acid (IAA) production were also present. A decreasing trend in the activities was
      observed with increasing salinity levels. Isolates JN6, BP8, and MJ4 showed the
      highest ARA activity, ammonia excretion, and IAA production. The performance of
      isolates like BNC2 with good ARA activity, ammonia excretion, and IAA production
      and isolated from a very strongly saline soil should be further evaluated under
      high-saline conditions.

PMID- 23553357
TI  - Once-weekly exenatide: an extended-duration glucagon-like peptide agonist for the
      treatment of type 2 diabetes mellitus.
AB  - Type 2 diabetes affects over 25 million people in the United States. There are
      many treatment options for patients with type 2 diabetes, but current treatments
      must be administered on a daily basis. Once-weekly exenatide, an extended
      duration glucagon-like peptide-1 (GLP-1) agonist, provides an option for patients
      to take a drug weekly, with pharmacotherapeutic effects that are superior to
      twice-daily exenatide and sitagliptin and comparable to insulin glargine. The
      DURATION trials provide evidence that once-weekly exenatide reduces hemoglobin
      A1c , and may result in weight loss. Once-weekly exenatide is marketed as a 2-mg
      injection administered subcutaneously once every 7 days. Adverse effects of once
      weekly exenatide include gastrointestinal effects, hypoglycemia, injection-site
      reactions, pancreatitis, and antibody development. Patients with a self history
      or family history of thyroid tumors should avoid using once-weekly exenatide.
      Delayed gastric absorption with orally administered drugs is possible, and
      monitoring should occur to avoid loss in therapeutic effect. Once-weekly
      exenatide is a new extended-duration agent with efficacy and tolerability
      profiles comparative to older therapies. Appropriate patients for once-weekly
      exenatide would be those who are concerned about weight gain, hypoglycemia, or
      those who do not wish to administer injections daily.

PMID- 23553358
TI  - Staff time and motion assessment for administration of erythropoiesis-stimulating
      agents: a two-phase pilot study in clinical oncology practices.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are used for the management
      of anaemia in patients with non-myeloid malignancies where anaemia is due to the
      effect of concomitant myelosuppressive chemotherapy. Assessing the impact of
      different ESA dosing regimens on office staff time and projected labour costs is
      an important component of understanding the potential for optimization of
      oncology practice efficiencies. OBJECTIVES: A two-phase study was conducted to
      evaluate staff time and labour costs directly associated with ESA administration
      in real-world oncology practice settings among cancer patients undergoing
      chemotherapy. The objective of Phase 1 was to determine the mean staff time
      required for the process of ESA administration in patients with anaemia due to
      concomitantly administered chemotherapy. The objective of Phase 2 was to quantify
      and compare the mean staff time and mean labour costs of ESA administered once
      weekly (qw) with ESA once every 3 weeks (q3w) over an entire course of
      chemotherapy. METHODS: Phase 1 was a prospective, cross-sectional time and motion
      study conducted in six private oncology practices in the US based on nine steps
      associated with ESA administration. Using findings from Phase 1, Phase 2 was
      conducted as a retrospective chart review to collect data on the number and types
      of visits in two private oncology practices for patients receiving a complete
      course of myelosuppressive chemotherapy. RESULTS: In Phase 1, the mean total time
      that clinic staff spent on ESA administration was 23.2 min for patient visits
      that included chemotherapy administration (n(chemo) = 37) and 21.5 min when only
      ESA was administered (n(ESAonly) = 36). In Phase 2, the mean duration of
      treatment was significantly longer for q3w than qw (53.84 days for qw vs. 113.38
      for q3w, p < 0.0001); thus, analyses were adjusted using analysis of covariance
      (ANCOVA) for episode duration for between-group comparisons. Following adjustment
      by ANCOVA, qw darbepoetin alfa (DA) patients (n(qw) = 83) required more staff
      time for ESA + chemotherapy visits and ESA-only visits than q3w patients (n(q3w)
      = 118) over a course of chemotherapy. Overall, mean total staff time expended per
      chemotherapy course was greater for patients receiving qw versus q3w DA. Weekly
      DA dosing was associated with greater projected mean labour costs ($US38.16 vs.
      $US31.20 [average for 2007-2010]). CONCLUSIONS: The results from this real-world
      study demonstrate that oncology practices can attain staff time and labour costs
      savings through the use of q3w ESA. The degree of savings depends on the
      individual oncology practice's staffing model and ESA administration processes,
      including those that allow for optimized synchronization of patient visits for
      ESA and chemotherapy administration. These findings indicate that additional
      research using standard ESA administration protocols for longer periods of time
      with a larger number of oncology practices and patients should be conducted to
      confirm these findings.

PMID- 23553363
TI  - Nocardioides panaciterrulae sp. nov., isolated from soil of a ginseng field, with
      ginsenoside converting activity.
AB  - A Gram-positive, coccoid to rod-shaped, non-spore-forming bacterium, designated
      Gsoil 958(T), was isolated from soil of a ginseng field located in Pocheon
      province in South Korea. This bacterium was characterized in order to determine
      its taxonomic position by using a polyphasic approach. Strain Gsoil 958(T) was
      observed to grow well at 25-30  degrees C and at pH 7.0 on R2A and nutrient agar
      without NaCl supplementation. Strain Gsoil 958(T) was determined to have beta
      glucosidase activity and the ability to transform ginsenoside Rb1 (one of the
      dominant active components of ginseng) to F2 via gypenoside XVII and Rd. On the
      basis of 16S rRNA gene sequence similarity, strain Gsoil 958(T) was shown to
      belong to the family Nocardioidaceae and related most closely to Nocardioides
      koreensis MSL-09(T) (97.6 % 16S rRNA gene sequence similarity), Nocardioides
      aquiterrae GW-9(T) (97.0 %), and Nocardioides sediminis MSL-01(T) (97.0 %). The
      sequence similarities with other validly named species within the genus
      Nocardioides were less than 96.8 %. Strain Gsoil 958(T) was characterized
      chemotaxonomically as having LL-2,6-diaminopimelic acid in the cell-wall
      peptidoglycan, MK-8(H4) as the predominant menaquinone, and iso-C16:0, iso-C16:1
      H, iso-C14:0, iso-C15:0 were identified as the major fatty acids. The G + C
      content of genomic DNA was determined to be 70.8 mol %. The chemotaxonomic
      properties and phenotypic characteristics supported the affiliation of strain
      Gsoil 958(T) to the genus Nocardioides. The results of both physiological and
      biochemical tests allowed for differentiation of strain Gsoil 958(T) from the
      recognized Nocardioides species. Therefore, strain Gsoil 958(T) is considered to
      represent a novel species of the genus Nocardioides, for which the name
      Nocardioides panaciterrulae sp. nov. is proposed, with the type strain Gsoil
      958(T) (KACC 14271(T) = KCTC 19471(T) = DSM 21350(T)).

PMID- 23553364
TI  - Anomalous superconducting state in LiFeAs implied by the 75As Knight shift
      measurement.
AB  - (75)As NMR investigation of a single crystal of superconducting LiFeAs is
      presented. The Knight shift and the in situ ac susceptibility measurements as a
      function of temperature and external field are indicative of two superconducting
      (SC) transition temperatures, each of which is associated with its own upper
      critical field. Strikingly, the Knight shift maintains its normal state value
      over a temperature range in the SC state before it drops abruptly, being
      consistent with spin-singlet pairing. Together with our previous NMR study, the
      anomalous SC state featuring the constant Knight shift is attributed to the
      extremely sensitive SC properties of LiFeAs, probably stemming from its proximity
      to a critical instability.

PMID- 23553366
TI  - Preventing nasogastric tube injury: is there a better way?

PMID- 23553367
TI  - Urinary d-lactate levels reflect renal function in aristolochic acid-induced
      nephropathy in mice.
AB  - Urinary d-lactate is highly correlated to diabetic nephropathy - a progressive
      kidney disease in renal glomeruli. In this study, we used a C3H/3e mouse model to
      investigate the relationship between urinary d-lactate and aristolochic acid
      nephropathy where the glomerular structure is not affected. The nephropathy was
      induced using intravenous injections of aristolochic acid at a dosage of 10 mg/kg
      per day for 5 days and was characterized biochemically and histologically. The
      urinary excretions of proteins, N-acetyl-beta-d-glucosaminidase and serum
      creatinine were determined and connected to histological conventional findings.
      Urinary d-lactate was analyzed using column-switching high-performance liquid
      chromatography with fluorescence detection. The results showed a remarkable
      increase of urinary markers, including of urinary proteins and N-acetyl-beta-d
      glucosaminidase, and the histological examination confirmed a diagnosis of acute
      tubule necrosis. The ratio of d-lactate to creatinine in the urine of
      aristolochic acid-treated mice was approximately 36 times greater than that of
      the mice in the control group (p < 0.05). The ratios for the two groups of mice
      were 311.00 +/- 71.70 and 8.60 +/- 1.80 umol/mmol creatinine, respectively. These
      data confirm in vivo that urinary d-lactate reflects renal injury conditions in
      aristolochic acid-treated mice and may be a marker for the assessment of
      nephropathy.

PMID- 23553365
TI  - Targeting the glutamatergic system for the treatment of HIV-associated
      neurocognitive disorders.
AB  - The accumulation of excess glutamate in the extracellular space as a consequence
      of CNS trauma, neurodegenerative diseases, infection, or deregulation of
      glutamate clearance results in neuronal damage by excessive excitatory
      neurotransmission. Glutamate excitotoxicity is thought to be one of several
      mechanisms by which HIV exerts neurotoxicity that culminates in HIV-associated
      neurocognitive disorders (HAND). Excess glutamate is released upon HIV infection
      of macrophage/microglial cells and has been associated with neurotoxicity
      mediated by gp120, transactivator of transcription (Tat) and other HIV proteins.
      Several strategies have been used over the years to try to prevent glutamate
      excitotoxicity. Since the main toxic effects of excess glutamate are thought to
      be due to excitotoxicity from over activation of glutamate receptors, antagonists
      of these receptors have been popular therapeutic targets. Early work to
      ameliorate the effects of excess extracellular glutamate focused on NMDA receptor
      antagonism, but unfortunately, potent blockade of this receptor has been fraught
      with side effects. One alternative to direct receptor blockade has been the
      inhibition of enzymes responsible for the production of glutamate such as
      glutaminase and glutamate carboxypeptidase II. Another approach has been to
      regulate the transporters responsible for modulation of extracellular glutamate
      such as excitatory amino acid transporters and the glutamate-cystine antiporter.
      There is preliminary experimental evidence that these approaches have potential
      therapeutic utility for the treatment of HAND. These efforts however, are at an
      early stage where the next steps are dependent on the identification of drug-like
      inhibitors as well as the development of predictive neuroAIDS animal models.

PMID- 23553369
TI  - Attractive electron-electron interactions within robust local fitting
      approximations.
AB  - An analysis of Dunlap's robust fitting approach reveals that the resulting two
      electron integral matrix is not manifestly positive semidefinite when local
      fitting domains or non-Coulomb fitting metrics are used. We present a highly
      local approximate method for evaluating four-center two-electron integrals based
      on the resolution-of-the-identity (RI) approximation and apply it to the
      construction of the Coulomb and exchange contributions to the Fock matrix. In
      this pair-atomic resolution-of-the-identity (PARI) approach, atomic-orbital (AO)
      products are expanded in auxiliary functions centered on the two atoms associated
      with each product. Numerical tests indicate that in 1% or less of all Hartree
      Fock and Kohn-Sham calculations, the indefinite integral matrix causes
      nonconvergence in the self-consistent-field iterations. In these cases, the two
      electron contribution to the total energy becomes negative, meaning that the
      electronic interaction is effectively attractive, and the total energy is
      dramatically lower than that obtained with exact integrals. In the vast majority
      of our test cases, however, the indefiniteness does not interfere with
      convergence. The total energy accuracy is comparable to that of the standard
      Coulomb-metric RI method. The speed-up compared with conventional algorithms is
      similar to the RI method for Coulomb contributions; exchange contributions are
      accelerated by a factor of up to eight with a triple-zeta quality basis set. A
      positive semidefinite integral matrix is recovered within PARI by introducing
      local auxiliary basis functions spanning the full AO product space, as may be
      achieved by using Cholesky-decomposition techniques. Local completion, however,
      slows down the algorithm to a level comparable with or below conventional
      calculations.

PMID- 23553368
TI  - Tibolone induces serotonin, estrogen, and progesterone receptor expression but
      not contractile response to serotonin in the rat uterus.
AB  - Most studies on the effect of tibolone on the uterus have focused on the
      endometrium dismissing the importance of the myometrium. The aim of the present
      study was to investigate some estrogen-like actions of tibolone in the uterus
      assessed by: 1) the expression of estrogen, progesterone, and serotonin
      receptors, and 2) the myometrial contraction induced by serotonin. Estradiol (250
      MUg), progesterone (50 mg), or testosterone (25 mg) pellets were implanted to
      ovariectomized rats. Tibolone (0.5 mg/day) was orally administered. An implanted
      pellet containing vehicle or an equivalent volume of water p.o., were used as
      controls. Sixty days after beginning the treatments, rats were killed and uterus
      removed. One horn was processed to evaluate estrogen-alpha, progesterone A and B,
      and serotonin-2A receptors expression, and the other one was used for studying
      contraction to serotonin and 60 mM potassium solution. The present data showed
      that tibolone-induced expression of estrogen, progesterone, and serotonin
      receptors, but did not induce uterine contractile response to either serotonin or
      potassium solution. These findings suggest that, in the uterus, tibolone may
      exert molecular estrogenic actions such as the induction of receptor expression,
      but not a physiological response as the estrogen-dependent contraction to
      serotonin. 

PMID- 23553370
TI  - A systematic review of surgical outcomes for advanced juvenile nasopharyngeal
      angiofibroma with intracranial involvement.
AB  - OBJECTIVES/HYPOTHESIS: Although transnasal endoscopic resection has become an
      established treatment for most juvenile nasopharyngeal angiofibroma (JNA),
      surgical management of JNA with intracranial extension remains challenging. This
      study systematically reviews the JNA literature to determine surgical outcomes.
      STUDY DESIGN: Systematic review. METHODS: A systematic search of the PubMed was
      undertaken using a combination of MeSH terms: angiofibroma, nasopharynx. The
      search was limited to articles published in the English language between January
      1990 and April 2012. Each article was reviewed to identify sufficient individual
      data on patients treated for JNA, defined as reporting on demographics, JNA
      stage, the specific surgical approach, complications, and length of follow-up for
      each patient. RESULTS: A total of 72 patients from 15 studies were included in
      this review. The mean age was 15.7 years. The mean follow-up period was 47
      months. Most patients had a craniofacial procedure. The overall mean estimated
      intraoperative blood loss was 1,709 mL. Preoperative embolization resulted in
      significantly less blood loss. The most common complications were sinonasal and
      neurological. Facial paresthesia was reported in 16%, followed by ophthalmoplegia
      (12%) and intranasal crusting (12%). Recurrence was reported in 13 patients
      (18%), which were detected between 7 and 26 months during the follow-up period.
      Overall, 86% of the cohort was free of disease. CONCLUSIONS: Surgical management
      of JNA with intracranial extension is complex and requires an expert
      multidisciplinary team. Although craniofacial approaches appear to be the current
      standard of treatment, there is increased experienced-based evidence that
      endoscopic resection of large tumors or endoscopic-assisted resection is feasible
      in expert hands. LEVEL OF EVIDENCE: 3a.

PMID- 23553371
TI  - Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by
      a toxin targeted through epidermal growth factor and urokinase receptors.
AB  - Targeted toxins have the potential to overcome intrinsic or acquired resistance
      of cancer cells to conventional cytotoxic agents. Here, we hypothesized that
      EGFuPA-toxin, a bispecific ligand-targeted toxin (BLT) consisting of a
      deimmunized Pseudomonas exotoxin (PE) conjugated to epidermal growth factor and
      urokinase, would efficiently target and kill cells derived from canine
      hemangiosarcoma (HSA), a highly chemotherapy resistant tumor, as well as cultured
      hemangiospheres, used as a surrogate for cancer stem cells (CSC). EGFuPA-toxin
      showed cytotoxicity in four HSA cell lines (Emma, Frog, DD-1 and SB) at a
      concentration of <=100 nM, and the cytotoxicity was dependent on specific ligand
      receptor interactions. Monospecific targeted toxins also killed these
      chemoresistant cells; in this case, a "threshold" level of EGFR expression
      appeared to be required to make cells sensitive to the monospecific EGF-toxin,
      but not to the monospecific uPA-toxin. The IC50 of CSCs was higher by
      approximately two orders of magnitude as compared to non-CSCs, but these cells
      were still sensitive to EGFuPA-toxin at nanomolar (i.e., pharmacologically
      relevant) concentrations, and when targeted by EGFuPA-toxin, resulted in death of
      the entire cell population. Taken together, our results support the use of these
      toxins to treat chemoresistant tumors such as sarcomas, including those that
      conform to the CSC model. Our results also support the use of companion animals
      with cancer for further translational development of these cytotoxic molecules.

PMID- 23553373
TI  - The use of propensity scores and observational data to estimate randomized
      controlled trial generalizability bias.
AB  - Although randomized controlled trials are considered the 'gold standard' for
      clinical studies, the use of exclusion criteria may impact the external validity
      of the results. It is unknown whether estimators of effect size are biased by
      excluding a portion of the target population from enrollment. We propose to use
      observational data to estimate the bias due to enrollment restrictions, which we
      term generalizability bias. In this paper, we introduce a class of estimators for
      the generalizability bias and use simulation to study its properties in the
      presence of non-constant treatment effects. We find the surprising result that
      our estimators can be unbiased for the true generalizability bias even when all
      potentially confounding variables are not measured. In addition, our proposed
      doubly robust estimator performs well even for mis-specified models.

PMID- 23553372
TI  - Interferon-gamma mediates anemia but is dispensable for fulminant toll-like
      receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice.
AB  - OBJECTIVE: Macrophage activation syndrome (MAS) is a devastating cytokine storm
      syndrome complicating many inflammatory diseases and characterized by fever,
      pancytopenia, and systemic inflammation. It is clinically similar to
      hemophagocytic lymphohistiocytosis (HLH), which is caused by viral infection of a
      host with impaired cellular cytotoxicity. Murine models of MAS and HLH illustrate
      that interferon-gamma (IFNgamma) is the driving stimulus for hemophagocytosis and
      immunopathology. This study was undertaken to investigate the inflammatory
      contributors to a murine model of Toll-like receptor 9 (TLR-9)-induced fulminant
      MAS. METHODS: Wild-type, transgenic, and cytokine-inhibited mice were treated
      with an IL-10 receptor blocking antibody and a TLR-9 agonist, and parameters of
      MAS were evaluated. RESULTS: Fulminant MAS was characterized by dramatic
      elevations in IFNgamma, IL-12, and IL-6 levels. Increased serum IFNgamma levels
      were associated with enhanced IFNgamma production within some hepatic cell
      populations but also with decreased numbers of IFNgamma-positive cells.
      Surprisingly, IFNgamma-knockout mice developed immunopathology and
      hemophagocytosis comparable to that seen in wild-type mice. However, IFNgamma
      knockout mice did not become anemic and had greater numbers of splenic erythroid
      precursors. IL-12 neutralization phenocopied disease in IFNgamma-knockout mice.
      Interestingly, type I IFNs contributed to the severity of hypercytokinemia and
      weight loss, but their absence did not otherwise affect MAS manifestations.
      CONCLUSION: These data demonstrate that both fulminant MAS and hemophagocytosis
      can arise independently of IFNgamma, IL-12, or type I IFNs. They also suggest
      that IFNgamma-mediated dyserythropoiesis, not hemophagocytosis, is the dominant
      cause of anemia in fulminant TLR-9-induced MAS. Thus, our data establish a novel
      mechanism for the acute anemia of inflammation, but suggest that a variety of
      triggers can result in hemophagocytic disease.

PMID- 23553374
TI  - Color Doppler sonography as an adjunct to repeat uterine evacuation for
      gestational trophoblastic disease: case report.
AB  - Repeat uterine evacuation is a therapeutic option for preserving fertility in
      patients with gestational trophoblastic neoplasms and chemoresistance, but
      remains controversial due to the risks of hemorrhage and perforation. A 25-year
      old patient with low-risk gestational trophoblastic neoplasm became
      chemoresistant; however, chemotherapy reduced intrauterine tumor vascularity as
      observed by color Doppler sonography, suggesting that patients could undergo
      uterine evacuation without major risk of bleeding. After 18 months, she achieved
      a normal pregnancy. Serial assessment of tumor vascularity with color Doppler
      sonography may provide information regarding the appropriate time to perform a
      repeat uterine evacuation without significant bleeding.

PMID- 23553375
TI  - Dermoscopic evaluation of nodular melanoma.
AB  - IMPORTANCE: Nodular melanoma (NM) is a rapidly progressing potentially lethal
      skin tumor for which early diagnosis is critical. OBJECTIVE: To determine the
      dermoscopy features of NM. DESIGN: Eighty-three cases of NM, 134 of invasive non
      NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic
      tumors were scored for dermoscopy features using modified and previously
      described methods. Lesions were separated into amelanotic/hypomelanotic or
      pigmented to assess outcomes. SETTING: Predominantly hospital-based clinics from
      5 continents. MAIN OUTCOME MEASURES: Sensitivity, specificity, and odds ratios
      for features/models for the diagnosis of melanoma. RESULTS: Nodular melanoma
      occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive
      non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM;
      in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs
      0.8%), large-diameter vessels, areas of homogeneous blue pigmentation,
      symmetrical shape, predominant peripheral vessels, blue-white veil, pink color,
      black color, and milky red/pink areas. Pigmented NM less frequently displayed an
      atypical broadened network, pigment network or pseudonetwork, multiple blue-gray
      dots, scarlike depigmentation, irregularly distributed and sized brown dots and
      globules, tan color, irregularly shaped depigmentation, and irregularly
      distributed and sized dots and globules of any color. The most important positive
      correlating features of pigmented NM vs nodular nonmelanoma were peripheral black
      dots/globules, multiple brown dots, irregular black dots/globules, blue-white
      veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to
      classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both
      nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for
      amelanotic/hypomelanotic NM (84%). A method for diagnosing
      amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave
      a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE: When a
      progressively growing, symmetrically patterned melanocytic nodule is identified,
      NM needs to be excluded.

PMID- 23553377
TI  - A preliminary metagenomic study of puer tea during pile fermentation.
AB  - BACKGROUND: Up to now, there has been no report on the taxonomic and functional
      analysis of the microbial community in fermenting puer tea by pyrosequencing. In
      this study, metagenomic pyrosequencing was first used in fermenting puer tea to
      delineate a relatively comprehensive overview of the microbial taxonomy while
      also preliminarily characterising the functional ontologies of microbial genes
      present in puer tea pile fermentation. RESULTS: A total of 251 738 pyrosequencing
      reads (9197 contigs and 145 402 singletons) were generated by pyrosequencing.
      Taxonomic analysis revealed three dominant bacterial phyla, Actinobacteria
      (30.08%), Proteobacteria (24.47%) and Firmicutes (20.23%), and one dominant
      eukaryotic phylum, Ascomycota (15.21%) [corrected]. A total of 58 664 hits were
      categorised into 28 functional subsystems based on the SEED database. Moreover,
      two categories, 'metabolism of terpenoids and polyketides' and 'biosynthesis of
      other secondary metabolites', were selectively analysed and 69 enzyme genes were
      presented in 16 pathways. CONCLUSION: The dominant microbes of puer tea
      fermentation were bacteria in the present study, and yeasts rather than moulds
      accounted for the overwhelming majority of Eukaryota. The analysis of functional
      genes and metabolic pathways will be helpful for further study of the mechanism
      of puer tea fermentation at molecular level.

PMID- 23553378
TI  - Five adult laryngeal venous malformation cases treated effectively with
      sclerotherapy.
AB  - OBJECTIVES/HYPOTHESIS: Laryngeal venous malformation is a comparatively rare
      condition in adults. It presents as a livid or bluish mass that may cause
      bleeding, hoarseness, stridor, and even difficulty in breathing. So far,
      treatment has largely consisted of laser therapy and surgical removal. Five cases
      of adult laryngeal venous malformations that were treated by sclerotherapy (local
      injection of monoethanolamine oleate solution) are reported. All lesions
      disappeared after one or two treatment sessions, and two of the five cases that
      presented recently were cured in the outpatient clinic setting with no sequelae.
      Sclerotherapy with monoethanolamine oleate is a safe, easy, and effective
      treatment for laryngeal venous malformations.

PMID- 23553379
TI  - Baseline albumin is associated with worsening renal function in patients with
      acute decompensated heart failure receiving continuous infusion loop diuretics.
AB  - STUDY OBJECTIVES: To identify baseline predictors of worsening renal function
      (WRF) in an acute decompensated heart failure (ADHF) patient population receiving
      continuous infusion loop diuretics. DESIGN: Retrospective observational analysis.
      SETTING: Academic tertiary medical center. PATIENTS: A total of 177 patients with
      ADHF receiving continuous infusion loop diuretics from January 2006 through June
      2009. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 61 years, 63% were
      male, ~45% were classified as New York Heart Association functional class III,
      and the median length of loop diuretic infusion was 4 days. Forty-eight patients
      (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox
      regression time-to-event analysis was used to determine the time to WRF based on
      different demographic and clinical variables. Baseline serum albumin 3 g/dl or
      less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95%
      confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite
      adjustments for other covariates. CONCLUSION: Serum albumin 3 g/dl or less is a
      practical baseline characteristic associated with the development of WRF in
      patients with ADHF receiving continuous infusion loop diuretics.

PMID- 23553380
TI  - Prescribing exercise for women.
AB  - One- half of women in the United States do not meet the weekly dose of physical
      activity recommended by the Centers for Disease Control. Many women could benefit
      tremendously if they were to adopt a more active lifestyle. Health benefits from
      exercise include lowering the risk for cardiovascular disease, slowing the rate
      of bone loss in osteoporosis, and improving mood during pregnancy. In this
      article, we review the health benefits that women may gain from physical activity
      and the recommendations for physical activity for adults in the United States. We
      offer evidence supporting use of the exercise prescription, discuss how to write
      an exercise prescription, and how to tailor the exercise prescription for women
      with particular medical problems.

PMID- 23553385
TI  - Preoperative imaging for resectable periampullary cancer: clinicopathologic
      implications of reported radiographic findings.
AB  - BACKGROUND: High-resolution, multiphase, computed tomography (CT) is a standard
      preoperative test prior to pancreatectomy, yet the clinical significance of
      routinely reported findings remains unknown. METHODS: We identified patients who
      underwent a pancreaticoduodenectomy for a periampullary adenocarcinoma (PA) over
      the previous 5 years and had a pancreas protocol CT at our institution.
      Clinicopathologic implications of reported CT findings were evaluated. RESULTS:
      There were 155 pancreatic ductal adenocarcinomas (PDA) and 47 non-pancreatic PAs.
      No mass was visualized on CT in 6 % of PDAs and 23 % of non-pancreatic PA. A size
      discrepancy of >=1 cm between radiographic and pathologic tumor diameters was
      observed in 40 % of PAs, with CT underestimating the size in most instances (75
      %). Radiographically enlarged lymph nodes were not associated with true lymph
      node metastases in PDAs (70 % lymph node positive cases were enlarged on CT vs 74
      % lymph node negative, p = 0.5), but were associated with a preoperatively placed
      biliary endoprosthesis (63 % with endoprosthesis were enlarged vs 37 % no
      endoprosthesis, p = 0.013). Major visceral vessel involvement on CT was not
      associated with a vascular resection (3 % with CT vessel involvement vs 2 %
      without, p = 0.8) or a positive uncinate resection margin (24 vs 20 %,
      respectively, p = 0.6). DISCUSSION: While dedicated pancreas protocol CT provides
      unprecedented detail, the test may lead to overinterpretation of the extent of
      disease in some instances. A radiographic suggestion of enlarged lymph nodes and
      vascular involvement does not necessarily preclude exploration with curative
      intent. CTs with local disease should be reported in an objective template and
      carefully reviewed by a multidisciplinary group of surgeons, radiologists, and
      oncologists to avoid missing an opportunity for neoadjuvant therapy or cure by
      resection.

PMID- 23553387
TI  - [Rotator cuff tendon: ct and mr arthrography are comparably effective].

PMID- 23553386
TI  - [Concentric Sclerosis Balo: A rare Variant of Multiple Sclerosis].

PMID- 23553388
TI  - [Prostate cancer: mri diagnosis and factors influencing outcome].

PMID- 23553389
TI  - [CT of the liver: Less radiation dose by a combination of ATVS and ATCM].

PMID- 23553390
TI  - [Brain substance loss: healthy subjects have faster atrophy with advancing age].

PMID- 23553391
TI  - [In-stent stenosis: detailed diagnostics with new generation ct scanners].

PMID- 23553392
TI  - [Knee: Improved representation in MRI].

PMID- 23553393
TI  - [Tuberculosis and HIV infection: mediastinal lymph nodes on CT].

PMID- 23553404
TI  - Prenatal characteristics of false negative cases from first-trimester screening
      of Down syndrome (trisomy 21).

PMID- 23553405
TI  - Comment on "MeDIP real-time qPCR of maternal peripheral blood reliably identifies
      trisomy 21".

PMID- 23553406
TI  - Author's response regarding "MeDIP-qPCR approach for non-invasive prenatal
      diagnosis of Down syndrome: accuracy and reproducibility".

PMID- 23553407
TI  - Using surrogate biomarkers to improve measurement error models in nutritional
      epidemiology.
AB  - Nutritional epidemiology relies largely on self-reported measures of dietary
      intake, errors in which give biased estimated diet-disease associations. Self
      reported measurements come from questionnaires and food records. Unbiased
      biomarkers are scarce; however, surrogate biomarkers, which are correlated with
      intake but not unbiased, can also be useful. It is important to quantify and
      correct for the effects of measurement error on diet-disease associations.
      Challenges arise because there is no gold standard, and errors in self-reported
      measurements are correlated with true intake and each other. We describe an
      extended model for error in questionnaire, food record, and surrogate biomarker
      measurements. The focus is on estimating the degree of bias in estimated diet
      disease associations due to measurement error. In particular, we propose using
      sensitivity analyses to assess the impact of changes in values of model
      parameters which are usually assumed fixed. The methods are motivated by and
      applied to measures of fruit and vegetable intake from questionnaires, 7-day diet
      diaries, and surrogate biomarker (plasma vitamin C) from over 25000 participants
      in the Norfolk cohort of the European Prospective Investigation into Cancer and
      Nutrition. Our results show that the estimated effects of error in self-reported
      measurements are highly sensitive to model assumptions, resulting in anything
      from a large attenuation to a small amplification in the diet-disease
      association. Commonly made assumptions could result in a large overcorrection for
      the effects of measurement error. Increased understanding of relationships
      between potential surrogate biomarkers and true dietary intake is essential for
      obtaining good estimates of the effects of measurement error in self-reported
      measurements on observed diet-disease associations.

PMID- 23553408
TI  - Head and neck trauma in Iraq and Afghanistan: different war, different surgery,
      lessons learned.
AB  - OBJECTIVES/HYPOTHESIS: The objectives are to compare and contrast the head and
      neck trauma experience in Iraq and Afghanistan and to identify trauma lessons
      learned that are applicable to civilian practice. STUDY DESIGN: A retrospective
      review of one head and neck surgeon's operative experience in Iraq and
      Afghanistan was performed using operative logs and medical records. METHODS: The
      surgeon's daily operative log book with patient demographic data and operative
      reports was reviewed. Also, patient medical records were examined to identify the
      preoperative and postoperative course of care. RESULTS: The head and neck trauma
      experiences in Iraq and Afghanistan were very different, with a higher percentage
      of emergent cases performed in Iraq. In Iraq, only 10% of patients were
      pretreated at a facility with surgical capabilities. In Afghanistan, 93% of
      patients were pretreated at such facilities. Emergent neck exploration for
      penetrating neck trauma and emergent airway surgery were more common in Iraq,
      which most likely accounted for the increased perioperative mortality also seen
      in Iraq (5.3% in Iraq vs. 1.3% in Afghanistan). Valuable lessons regarding soft
      tissue trauma repair, midface fracture repair, and mandible fracture repair were
      learned. CONCLUSION: The head and neck trauma experiences in Iraq and Afghanistan
      were very different, and the future training for mass casualty trauma events
      should reflect these differences. Furthermore, valuable head and neck trauma
      lessons learned in both war zones are applicable to the civilian practice of
      trauma. LEVEL OF EVIDENCE: Level 4.

PMID- 23553409
TI  - Prospective study of genital human papillomaviruses and nonmelanoma skin cancer.
AB  - Genital high-risk human papillomaviruses (HPVs) cause cervical cancer and are
      also found in a small proportion of nonmelanoma skin cancers (NMSCs). We used
      cancer registry linkages to follow the 856,000 serum donors included in the
      Southern Sweden Microbiology Biobank or the Janus Biobank in Norway, for incident
      skin cancers occurring up to 30 years after serum donation. Serum samples taken
      before diagnosis of squamous cell carcinoma (SCC) (N = 633), basal cell carcinoma
      (BCC) (N = 1990) or other NMSC (N = 153) and matched samples from control donors
      were tested for antibodies to the genital HPV types 16 and 18. Both HPV 16 and 18
      were associated with increased risk for SCC [odds ratio (OR) 1.6, 95% confidence
      interval (CI) 1.1-2.6 and OR 1.7, 95% CI 1.1-2.5, respectively] and other NMSC
      (OR 2.3, 95% CI 1.0-5.2 and OR 3.5, 95% CI 1.4-8.7, respectively), but not for
      BCC. Tumor blocks from HPV16 or 18 seropositive cases were tested with real-time
      polymerase chain reaction for presence of HPV16 or 18 DNA. No HPV18 DNA was found
      and only four of 79 SCC cases (two of which were from the perineum/perianal
      area), one of 221 BCC cases and zero of five cases with other NMSC contained
      HPV16 DNA. In conclusion, we found prospective evidence that HPV16 and 18
      antibodies associate with SCC and other NMSC risk, but not with BCC risk. As only
      a small proportion of seropositive subjects had evidence of the corresponding HPV
      DNA in the tumor, most of this excess risk is likely to be due to confounders
      associated with genital HPV infection.

PMID- 23553410
TI  - Concurrent somatotroph and plurihormonal pituitary adenomas in a cat.
AB  - An 8-year-old, male neutered, domestic longhair cat was referred for
      investigation of insulin-resistant diabetes mellitus. Routine haematology, serum
      biochemistry, urinalysis (including culture), total T4 and urine
      creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like
      growth factor-1 concentration was identified and a pituitary mass was
      subsequently documented. The cat was treated conservatively with the dopamine
      agonist L-deprenyl and was re-presented 16 months later for worsening polyuria,
      polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous
      abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was
      diagnosed based on abdominal ultrasonography, dexamethasone suppression testing
      and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with
      trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an
      opportunistic fungal infection and skin fragility syndrome 4.5 months after
      commencing treatment, and was euthanased. A double-pituitary adenoma comprising a
      discrete somatotroph adenoma and a separate plurihormonal adenoma (positive
      immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle
      stimulating hormone) was identified on post-mortem examination. These two
      pituitary adenomas were suspected to have arisen as independent neoplastic
      entities with the plurihormonal tumour either being clinically silent at the
      initial presentation or having developed over the subsequent 16 months. 

PMID- 23553411
TI  - Cochlear implantation for unilateral deafness with and without tinnitus: a case
      series.
AB  - OBJECTIVES/HYPOTHESIS: To investigate cochlear implantation (CI) in patients with
      unilateral deafness with and without tinnitus. STUDY DESIGN: Prospective case
      series of patients undergoing cochlear implantation for unilateral deafness and
      tinnitus in a tertiary academic unit. METHODS: Nine postlingually deafened
      subjects with unilateral hearing loss, with and without tinnitus ipsilaterally,
      and functional hearing in the contralateral ear were implanted with a standard
      electrode. Speech perception in noise was tested using the Bamford-Kowal-Bench
      presented at 65 dB SPL. The Speech, Spatial, and Qualities (SSQ) of Hearing Scale
      was used to evaluate the subjective perception of hearing outcomes, and the
      Tinnitus Reaction Questionnaire assessed the effect on tinnitus. RESULTS: All
      patients were implanted with the Med-El Flex soft electrode, Innsbruck, Austria.
      They are regularly wearing the speech processor and find it beneficial in
      improving their ability to hear, particularly in noise. Decrease of tinnitus
      perception and an improvement of sound localization sounds were also reported by
      these patients. CONCLUSION: In our case series, CI was successful for all nine
      patients, with improvement of speech recognition in noise, self-perceived
      improvement of hearing, and for tinnitus control. Several factors such as
      deafness duration, age of deafness onset, the presence of residual hearing,
      patient motivation, and the rehabilitation intensity need to be further
      investigated in order to understand their impact on performance after
      implantation. LEVEL OF EVIDENCE: 4.

PMID- 23553412
TI  - [Criteria for radiological assessment of therapy response: criteria-based
      appraisal].
AB  - Oncologic imaging and reporting are an important part of clinical trials and have
      to be performed according to standardized criteria that clearly define how
      certain changes in the size and number of tumorous lesions have to be rated.
      Knowledge of these criteria is not only crucial when interpreting cases for a
      clinical trial but may also be used as guidelines for everyday clinical reporting
      as they aid decision making and can increase the validity of radiologic
      reporting.This article summarizes the most important and frequently used
      criteria: the response evaluation criteria in solid tumors (RECIST) criteria
      which are only used in solid malignancies, the Choi criteria that have been
      designed for the assessment of gastrointestinal stroma tumors (GIST), and the
      Cheson criteria that are applied to malignant lymphomas. The compilation of these
      criteria is designed to be used as a repetitorium for experts and can also serve
      as training guidelines for junior radiologists who want to become involved in
      clinical trial reporting.

PMID- 23553413
TI  - [Unilateral leg swelling post partum].

PMID- 23553414
TI  - Reduction of hexavalent chromium by a novel Ochrobactrum sp. - microbial
      characteristics and reduction kinetics.
AB  - A Gram negative hexavalent chromium (Cr(VI)) reducing bacteria, Ochrobactrum sp.
      Cr-B4 (genbank accession number: JF824998) was isolated from the aerator water of
      an activated sludge process of a wastewater treatment facility of a dye and
      pigment based specialty chemical industry. It showed a resistance for 1000 mg L(
      1) Cr(VI). It exhibited resistance against other heavy metal ions like Ni(2+)
      (900 mg L(-1) ), Cu(2+) (500 mg L(-1) ), Pb(2+) (800 mg L(-1) ), and Cd(2+) (250
      mg L(-1) ), Zn(2+) (700 mg L(-1) ), Fe(3+) (800 mg L(-1) ), and against selected
      antibiotics. Cr-B4 could efficiently reduce 200 mg L(-1) Cr(VI) completely in
      nutrient and LB media and could convert Cr(VI) to Cr(III) efficiently. Cr(VI)
      reduction in nutrient media followed allosteric enzyme kinetics with Km values of
      59.39 mg L(-1) and Vmax values of 47.03 mg L(-1)  h(-1) . The reduction in LB
      media followed Michaelis-Menten kinetics with Km values of 99.52 mg L(-1) and
      Vmax of 77.63 mg L(-1)  h(-1) . Scanning electron micrograms revealed the
      presence of extracellular polymeric secretions. 

PMID- 23553415
TI  - Patients with antineutrophil cytoplasmic antibody-associated vasculitis have
      defective Treg cell function exacerbated by the presence of a suppression
      resistant effector cell population.
AB  - OBJECTIVE: The development of pathogenic antineutrophil cytoplasmic antibodies
      (ANCAs) can result in systemic small vessel vasculitis. However, the breakdown in
      immune tolerance that results in the induction and persistence of ANCAs is not
      well understood. We undertook this study to test our hypothesis that abnormal T
      cell regulation is central to disease pathogenesis in patients with ANCA
      associated vasculitis (AAV). METHODS: Peripheral blood samples were obtained from
      62 patients with AAV and 19 healthy controls for flow cytometric analysis of CD4+
      T cell populations. Functional T cell studies were performed with fluorescence
      activated cell sorted CD4+ T cell populations stimulated with anti-CD3/anti-CD28.
      RESULTS: We demonstrated two separate abnormalities in T cell regulation in
      patients with AAV. First, we showed that the Treg cell frequency was increased in
      the peripheral blood of patients with active disease, but Treg cells from
      patients with AAV had decreased suppressive function. Treg cells from patients
      with active disease disproportionately used a FoxP3 isoform lacking exon 2, which
      might alter Treg cell function. Second, we identified a CD4+ T cell population
      with increased frequency that was resistant to Treg cell suppression, produced
      proinflammatory cytokines, and was antigen experienced. CONCLUSION: AAV is
      associated with disruption of the suppressive Treg cell network and with
      increased frequency of a distinct proinflammatory effector T cell subset that
      comprises the majority of peripheral CD4+ T cells.

PMID- 23553416
TI  - Epidemiology of unilateral sensorineural hearing loss with universal newborn
      hearing screening.
AB  - OBJECTIVES/HYPOTHESIS: Compare the epidemiology of pediatric unilateral
      sensorineural hearing loss before and after implementation of universal newborn
      hearing screening in Missouri. STUDY DESIGN: Inception cohort. METHODS: Charts of
      134 children born between January 1, 1990 and December 31, 2007, diagnosed with
      unilateral sensorineural hearing loss at a single institution in Missouri were
      reviewed to determine the effects of universal newborn hearing screening on age
      of detection and etiology of hearing loss. RESULTS: Mean age of detection
      declined from 4.4 (standard deviation [SD] 1.8) to 2.6 (SD 2.6) years of age,
      whereas the rate of detection by 6 months of age increased from 3% to 42%. The
      majority (58%) of cases had normal hearing at birth. The most common etiological
      category was unknown (41%) before screening and congenital (45%) after screening.
      The use of magnetic resonance imaging has increased by 21% (2-fold), whereas use
      of computed tomography has declined by 8% since 2002. Yields of connexin,
      Pendred, electrocardiogram, and syphilis testing were 0/48 and 2/31 before and
      after screening, respectively. CONCLUSIONS: Implementation of universal newborn
      hearing screening in Missouri is associated with a decrease in age of detection
      of unilateral sensorineural hearing loss. The majority of cases are either not
      present or not detectable at birth. The combination of hearing status at birth
      and imaging findings suggests that the majority of cases are congenital rather
      than of unknown etiology.

PMID- 23553417
TI  - Status and effect of pesticide residues in soils under different land uses of
      Andaman Islands, India.
AB  - Pesticides are shown to have a great effect on soil organisms, but the effect
      varies with pesticide group and concentration, and is modified by soil organic
      carbon content and soil texture. In the humid tropical islands of Andaman, India,
      no systematic study was carried out on pesticide residues in soils of different
      land uses. The present study used the modified QuEChERS method for multiresidue
      extraction from soils and detection with a gas chromatograph. DDT and its various
      metabolites, alpha-endosulfan, beta-endosulfan, endosulfan sulfate, aldrin, and
      fenvalerate, were detected from the study area. Among the different pesticide
      groups detected, endosulfan and DDT accounted for 41.7 % each followed by aldrin
      (16.7 %) and synthetic pyrethroid (8.3 %). A significantly higher concentration
      of pesticide residues was detected in rice-vegetable grown in the valley followed
      by rice-fallow and vegetable-fallow in the coastal plains. Soil microbial biomass
      carbon is negatively correlated with the total pesticide residues in soils, and
      it varied from 181.2 to 350.6 mg kg(-1). Pesticide residues have adversely
      affected the soil microbial populations, more significantly the bacterial
      population. The Azotobacter population has decreased to the extent of 51.8 %
      while actinomycetes were the least affected though accounted for 32 % when
      compared to the soils with no residue. 

PMID- 23553418
TI  - Supersymmetry in spherical molecules and fullerenes under perpendicular magnetic
      fields.
AB  - Methods of supersymmetric quantum mechanics are used to obtain analytical
      solutions for massless Dirac electrons in spherical molecules, including
      fullerenes, in the presence of magnetic fields. The solutions for Dirac massive
      charges are also obtained via the solutions of the Dirac-Weyl equation.

PMID- 23553419
TI  - The role of PSD-95 in the rearrangement of Kv1.3 channels to the immunological
      synapse.
AB  - Establishment of the immunological synapse (IS) between T lymphocytes and antigen
      presenting cells is a key step in the adaptive immune response. Several proteins
      accumulate in the IS, such as the Kv1.3 potassium channel; however, the mechanism
      of this translocation is unknown. PSD-95 and SAP97 are adaptor proteins that
      regulate the polarized cell surface expression and localization of Kv1 channels
      in neurons. We investigated whether these proteins affect the redistribution of
      Kv1.3 into the IS in non-excitable human T cells. We show here that PSD-95 and
      SAP97 are expressed in Jurkat and interact with the C terminus of Kv1.3.
      Disruption of the interaction between PSD-95 or SAP97 and Kv1.3 in Jurkat was
      realized by the expression of a C-terminal truncated Kv1.3, which lacks the
      binding domain for these proteins, or by the knockdown of the expression of PSD
      95 or SAP97 using specific shRNA. Expression of the truncated Kv1.3 or knockdown
      of PSD-95, but not the knockdown of SAP97, inhibited the recruitment of Kv1.3
      into the IS; the fraction of cells showing polarized Kv1.3 expression upon
      engagement in an IS was significantly lower than in control cells expressing the
      full-length Kv1.3, and the rearrangement of Kv1.3 did not show time dependence.
      In contrast, Jurkat cells expressing the full-length channel showed marked time
      dependence in the recruitment into the IS peaking at 1 min after the conjugation
      of the cells. These results demonstrate that PSD-95 participates in the targeting
      of Kv1.3 into the IS, implying its important role in human T-cell activation.

PMID- 23553420
TI  - Double common bile duct with choledochal cyst and cholelithiasis: report of a
      case.
AB  - Double common bile duct (DCBD) is a rare congenital anomaly of the biliary
      system, often associated with biliary lithiasis, choledochal cyst,
      pancreaticobiliary maljunction (PBM), and upper gastrointestinal tract
      malignancies. We report a case of type I DCBD with choledochal cyst and
      cholelithiasis in a 52-year-old Chinese man. We also reviewed 24 cases of DCBD
      reported in the Chinese literature between 1965 and 2012. Most (58.3%) of these
      cases were classified as type I DCBD, with accompanying choledocholithiasis in
      79.2%, cholecystolithiasis in 37.5%, choledochal cyst in 33.3%, and PBM in 8.3%.
      There was no case of concomitant cancer. The type and coexistence of PBM with
      DCBD are clinically important because of its close implications with concomitant
      pathology. Most Chinese people with DCBD have type I. Moreover, the high
      incidences of choledochal cyst and biliary lithiasis and the extremely low
      incidences of PBM and biliary cancer are the major clinical characteristics of
      DCBD in China.

PMID- 23553421
TI  - Outcomes of combined modality therapy for patients with stage III or IV
      mediastinal malignant germ cell tumors.
AB  - PURPOSE: The treatment of primary mediastinal germ cell tumors with cisplatin
      based chemotherapy followed by surgery is an established practice; however, the
      prognosis has remained poor. This study reviews the survival outcomes of patients
      with primary mediastinal germ cell tumors to evaluate the efficacy of our
      treatment. METHODS: We retrospectively reviewed 11 consecutive patients with
      primary mediastinal germ cell tumors. RESULTS: We had treated four patients with
      seminomas and seven patients with non-seminomas. Ten patients had undergone
      cisplatin-based chemotherapy. All patients underwent complete resection. Two
      patients showed a failure of first-line chemotherapy and thus received salvage
      chemotherapies, including paclitaxel plus ifosfamide followed by high-dose
      carboplatin plus etoposide (TI-CE) with stem cell transplantation. One of them
      died of relapse 29 months later; while the other patient remained disease-free
      for 56 months postoperatively. The postoperative overall 3-year survival rates of
      the patients with non-seminomas and seminomas were 83 and 100%, respectively.
      CONCLUSION: Complete resection after establishing normalized or decreased at a
      low-level serum tumor markers plateau plays a crucial role in the management of
      patients with primary mediastinal malignant germ cell tumors.

PMID- 23553422
TI  - Prognosis following emergency surgery for ulcerative colitis in elderly patients.
AB  - PURPOSE: Since 2000, the incidence of ulcerative colitis (UC) in patients over 60
      years old has been rapidly increasing. We reviewed our surgical experience of
      elderly patients with UC treated at our hospital. METHODS: Patients aged 60 years
      or older at the time of surgery were defined as "elderly". The medical records of
      all elderly patients who underwent surgery for UC during a 26-year period were
      retrospectively analyzed. RESULTS: The prognosis of elderly patients who
      underwent emergency surgery was extremely poor: 8 (26.7 %) of 30 such patients
      died within 30 postoperative days (PODs), whereas only 1 (0.88 %) of 114 who
      underwent elective surgery died within 30 PODs. Respiratory tract infection and
      sepsis resulting from methicillin-resistant Staphylococcus aureus or mycotic
      infection were the most common causes of death after emergency surgery.
      CONCLUSION: The prognosis of elderly UC patients undergoing emergency surgery is
      very poor; thus, physicians and surgeons should collaborate to treat severe and
      fulminant disease, to optimize the timing of surgery. Early decisions about
      emergency surgery for UC will reduce postoperative mortality, especially in
      elderly patients.

PMID- 23553423
TI  - Telaprevir: clinical pharmacokinetics, pharmacodynamics, and drug-drug
      interactions.
AB  - This article provides an unbiased review of the pharmacokinetic, pharmacodynamic,
      and drug-drug interaction data of telaprevir, an NS3/4A protease inhibitor.
      Telaprevir is well absorbed with fatty food, moderately protein bound (59-76 %)
      with a large volume of distribution (~252 L), primarily metabolized by cytochrome
      P450 (CYP) 3A4 and P-glycoprotein, and is largely excreted into feces.
      Pharmacokinetic and pharmacodynamic parameters are well described in healthy
      subjects and individuals infected with hepatitis C virus (HCV), although only
      limited data are available in specific patient subpopulations. Telaprevir is
      recommended to be given at 750 mg by mouth every 8 h for 12 weeks, in combination
      with peginterferon and ribavirin (the standard care). The addition of telaprevir
      to the standard care regimen results in increased sustained virological response
      in treatment-naive patients (30 %) and treatment-experienced patients (up to 50
      %), and works synergistically to lower viral resistance. Telaprevir is a
      substrate and/or inhibitor of CYP3A4 and P-glycoprotein, and drug-drug
      interaction studies in humans have focused on these pathways. Based on our
      analysis, a few reported drug-drug interactions may be classified as clinically
      significant, but more experiments under dosing conditions that resemble those
      given in the clinic are needed to understand the relevance of some of the
      reported interactions. Future studies should focus on the
      pharmacokinetics/pharmacodynamics of telaprevir in special populations or
      patients with concomitant conditions that will likely co-exist with HCV
      infection, with an emphasis on establishing pharmacokinetic-pharmacodynamic
      relationships. In vitro characterization of other phase 1-3 metabolic pathways
      could assist in elucidating the mechanisms of the drug-drug interactions observed
      in humans. 

PMID- 23553424
TI  - Letter to the editor: pharmacokinetics of non-intravenous formulations of
      fentanyl.

PMID- 23553426
TI  - Targetoid lesions in the emergency department. Bed bug bites (Cimex lectularius)
      with targetoid lesions on initial presentation.

PMID- 23553425
TI  - An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab
      emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic
      sampling in patients with HER2-positive metastatic breast cancer.
AB  - BACKGROUND AND OBJECTIVE: Trastuzumab emtansine (T-DM1) is an antibody-drug
      conjugate recently approved by the US Food and Drug Administration for the
      treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic
      breast cancer previously treated with trastuzumab and taxane chemotherapy. It
      comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2
      targeted humanized monoclonal antibody trastuzumab via a stable linker. To
      characterize the pharmacokinetics of T-DM1 in patients with metastatic breast
      cancer, concentrations of multiple analytes were quantified, including serum
      concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated
      and unconjugated trastuzumab), as well as plasma concentrations of DM1. The
      clearance of T-DM1 conjugate is approximately 2 to 3 times faster than its parent
      antibody, trastuzumab. However, the clearance pathways accounting for this faster
      clearance rate are unclear. An integrated population pharmacokinetic model that
      simultaneously fits the pharmacokinetics of T-DM1 conjugate and total trastuzumab
      can help to elucidate the clearance pathways of T-DM1. The model can also be used
      to predict total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate
      pharmacokinetic data and sparse total trastuzumab pharmacokinetic data, thereby
      reducing the frequency of pharmacokinetic sampling. METHODS: T-DM1 conjugate and
      total trastuzumab serum concentration data, including baseline trastuzumab
      concentrations prior to T-DM1 treatment, from phase I and II studies were used to
      develop this integrated population pharmacokinetic model. Based on a hypothetical
      T-DM1 catabolism scheme, two-compartment models for T-DM1 conjugate and
      trastuzumab were integrated by assuming a one-step deconjugation clearance from T
      DM1 conjugate to trastuzumab. The ability of the model to predict the total
      trastuzumab pharmacokinetic profile based on T-DM1 conjugate pharmacokinetics and
      various sampling schemes of total trastuzumab pharmacokinetics was assessed to
      evaluate total trastuzumab sampling schemes. RESULTS: The final model reflects a
      simplified catabolism scheme of T-DM1, suggesting that T-DM1 clearance pathways
      include both deconjugation and proteolytic degradation. The model fits T-DM1
      conjugate and total trastuzumab pharmacokinetic data simultaneously. The
      deconjugation clearance of T-DM1 was estimated to be ~0.4 L/day. Proteolytic
      degradation clearances for T-DM1 and trastuzumab were similar (~0.3 L/day). This
      model accurately predicts total trastuzumab pharmacokinetic profiles based on T
      DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic
      data sampled at preinfusion and end of infusion in cycle 1, and in one additional
      steady state cycle. CONCLUSIONS: This semi-mechanistic integrated model links T
      DM1 conjugate and total trastuzumab pharmacokinetic data, and supports the
      inclusion of both proteolytic degradation and deconjugation as clearance pathways
      in the hypothetical T-DM1 catabolism scheme. The model attributes a faster T-DM1
      conjugate clearance versus that of trastuzumab to the presence of a deconjugation
      process and suggests a similar proteolytic clearance of T-DM1 and trastuzumab.
      Based on the model and T-DM1 conjugate pharmacokinetic data, a sparse
      pharmacokinetic sampling scheme for total trastuzumab provides an entire
      pharmacokinetic profile with similar predictive accuracy to that of a dense
      pharmacokinetic sampling scheme.

PMID- 23553427
TI  - Comparative studies on chemical parameters and antioxidant properties of stipes
      and caps of shiitake mushroom as affected by different drying methods.
AB  - BACKGROUND: Shiitake, the second most cultivated mushroom, is famous for its high
      nutritional value and medicinal properties. In this study, various chemical
      parameters and antioxidant properties of caps and stipes of shiitake mushroom
      dried by different methods (freeze-drying, shade drying and hot air drying) were
      comparatively investigated by spectrophotometric assays, high-performance liquid
      chromatography, 1,1'-diphenyl-2-picrylhydrazyl assay, ferric reducing power assay
      and lipid peroxidation inhibition assay. RESULTS: The contents of amino acids,
      neutral sugar and total phenolics in stipes were higher than those in caps of
      shiitake, while caps showed advantages in terms of their contents of protein and
      eritadenine. The chemical parameters and antioxidant activities of shiitake were
      significantly affected by the drying method used. CONCLUSION: The contents of
      total phenolics, amino acids and neutral sugar in stipes were higher than those
      in caps of shiitake, which suggested that stipes were more nutritional than caps
      in some respects. Hot air drying at 50  degrees C resulted in high total
      phenolic, amino acid, uronic acid and neutral sugar contents and antioxidant
      activities, which could be useful for the application of shiitake and related
      products in the food industry.

PMID- 23553428
TI  - Contrast-enhanced sonography for screening of vascular complication in recipients
      following living donor liver transplantation.
AB  - The purpose of this article is to discuss the role of CEUS for screening of
      vascular complication in recipients admitted to ICU following LDLT, effect of
      microbubble contrast agent on Doppler phenomenon, CEUS technique, and illustrate
      CEUS findings in recipients with complication following LDLT. CEUS can enhance
      the role of US in the diagnosis of postoperative vascular complication in
      recipients following living donor liver transplantation at the bedside.

PMID- 23553429
TI  - Leucine-rich diet improves the serum amino acid profile and body composition of
      fetuses from tumor-bearing pregnant mice.
AB  - Pregnancy is a complex process that can be jeopardized when associated with
      cancer, because of the coexistence of two complex metabolic conditions: a fetus
      and cancer. The aim of this study was to evaluate fetal growth in association
      with cancer development as well as the indirect effects produced by tumors in
      pregnant mice subjected to a leucine-rich diet, knowing that leucine
      supplementation can minimize the tumor effects by acting as a cell signaling
      agent to improve the protein synthesis process. We evaluated fetuses (n = 6) from
      NMRI pregnant mice fed either a control or a leucine-rich diet in either the
      presence or absence of an MAC16 colon adenocarcinoma or ascitic fluid
      inoculation. The fetal serum amino acids were separated using high-performance
      liquid chromatography, and fetal cytokine levels were analyzed using a
      microsphere-based multiplex immunoassay (Luminex xMAP). Fetal body composition
      was measured as the water, fat, and protein total content and total serum
      protein, albumin, and glucose content. Tumor growth resulted in a severe
      reduction in fetal body weight and protein content and increased fetal
      resorption, associated with placental weight decrease; these effects were
      minimized by a leucine-rich diet. Serum total protein and glucose content were
      reduced in fetuses from tumor-bearing dams but were reverted by nutritional
      supplementation. The serum amino acid profiles differed significantly between the
      tumor-bearing mice fed with a leucine-rich diet and controls. Certain tumor
      effects were reproduced in fetuses from ascitic fluid-injected dams, suggesting
      indirect effects of tumor growth. We conclude that certain effects of tumor
      growth can be mimicked by ascitic fluid injection and can be modulated by a
      leucine-rich diet.

PMID- 23553430
TI  - Prss37 is required for male fertility in the mouse.
AB  - In order to understand the mechanisms of mammalian fertilization, studies using
      genetically manipulated animals have provided us with plenty of interesting and
      valuable information on the genetic factors affecting male fertility. In the
      present work, we demonstrate for the first time that Prss37, a previously
      uncharacterized putative trypsin-like serine protease, is required for male
      fertility. Prss37 is highly and exclusively expressed in the testis of adult
      mice, especially in the elongating spermatids during spermiogenesis, and almost
      vanishes in the mature sperm of mice. Mice deficient for Prss37 show male
      infertility, but their mating activity, spermatogenesis, sperm morphology, and
      motility remain unaffected. In vivo fertilization assays revealed that Prss37(-/
      ) mice exhibited a markedly decreased fertilization rate (2.3% vs. 70% of that in
      control mice) accompanied by the defect in sperm migration from uterus into
      oviduct. In vitro study further showed sperm were incapable of sperm-egg
      recognition/binding when zona-intact eggs were exposed to Prss37(-/-) sperm, in
      which mature Adam3 was completely undetectable. Interestingly, however, Prss37(-/
      ) sperm were able to fertilize cumulus-intact oocytes in vitro. These data
      clearly indicate that Prss37 deficiency causes the absence of mature Adam3 in
      sperm and a defect in sperm migration from uterus into oviduct, which mainly
      accounts for male infertility of Prss37-null mice, while the defect in sperm-zona
      binding seems irrelevant to the fertilizing ability of Prss37(-/-) sperm.

PMID- 23553432
TI  - Community-acquired pneumonia and proton pump inhibitors.

PMID- 23553431
TI  - Maternal decidual macrophages inhibit NK cell killing of invasive
      cytotrophoblasts during human pregnancy.
AB  - Human pregnancy is an immunological paradox. Semiallogeneic (fetal) placental
      cells (extravillous cytotrophoblasts [CTBs]) invade the uterine lining (decidua),
      which contains a unique decidual natural killer (dNK) cell population, identified
      by the cell surface phenotype CD56(bright) CD16(-) CD3(-) and CD14(+) CD206(+)
      macrophages (dMac). Previous reports suggested that human dNK cells are not a
      threat to the fetoplacental unit because they are anergic. In contrast, here we
      showed that purified and exogenously stimulated dNK cells are capable killers of
      cellular targets, including semiallogeneic CTBs. However, dMacs in the decidual
      leukocyte (DL) population restrained dNK killing through a transforming growth
      factor beta1 (TGF-beta1)-dependent mechanism. Our findings support a new model
      whereby dNK cells, capable of killing CTBs, are prevented from doing so by
      neighboring macrophages, thus protecting the fetal cells from NK cell attack. We
      speculate that this mechanism would inhibit dNK cell-mediated killing, even under
      conditions where high levels of cytokines may stimulate dNK cells, which could
      pose a threat to the developing placenta. 

PMID- 23553433
TI  - Community-acquired pneumonia and proton pump inhibitors.

PMID- 23553434
TI  - Capsule commentary on Bauer et Al., health literacy and antidepressant adherence
      among adults with diabetes: implications for future research.

PMID- 23553435
TI  - NTHi induction of Cxcl2 and middle ear mucosal metaplasia in mice.
AB  - OBJECTIVES/HYPOTHESIS: Chronic otitis media (COM) develops after sustained
      inflammation and is characterized by secretory middle ear epithelial metaplasia
      and effusion, most frequently mucoid. Nontypeable Haemophilus influenzae (NTHi),
      the most common acute otitis media (OM) pathogen, is known to activate
      inflammation and mucin expression in vitro and in animal models of OM. The goals
      of this study were to examine histopathological and expression profiling
      epithelial effects of NTHi challenge in murine middle ears. STUDY DESIGN: In
      vitro and in vivo murine model of OM. METHODS: Weekly transtympanic inoculation
      of Balb/c mice with 300 MUg/ml of NTHi lysates versus saline was performed.
      Histopathologic analysis was carried out at 4 weeks. Expression microarray
      analysis was performed at 1 and 7 days. Microarray findings were validated in
      independent animal samples and in a cultured murine middle ear epithelial cell
      (mMEEC) line. RESULTS: Histopathologic analyses revealed middle ear mucosal
      thickening after NTHi exposure. Microarray analyses of inflammatory response
      genes which changed significantly demonstrated that the chemokine Cxcl2 had the
      largest fold-change, with significantly increased expression at 1 and 7 days
      after NTHi injection compared to either saline or no-injection (P <0.01).
      Validation by real-time qPCR revealed similar significantly increased relative
      mRNA levels for Cxcl2. NTHi lysates were also found to significantly upregulate
      the transcription of Cxcl2 in mMEEC in a time- and dose-dependent manner (P
      <0.05). CONCLUSIONS: Middle ear NTHi challenge in mice leads to chronic
      epithelial mucosal metaplasia and overexpression of inflammatory mediators, most
      notably Cxcl2. This finding is parallel to NTHi-mediated pulmonary mucosal
      metaplasia where Cxcl2 has been identified as an important inflammatory mediator.

PMID- 23553436
TI  - A note on the evaluation of novel biomarkers: do not rely on integrated
      discrimination improvement and net reclassification index.
AB  - The 'integrated discrimination improvement' (IDI) and the 'net reclassification
      index' (NRI) are statistics proposed as measures of the incremental prognostic
      impact that a new biomarker will have when added to an existing prediction model
      for a binary outcome. By design, both measures were meant to be intuitively
      appropriate, and the IDI and NRI formulae do look intuitively plausible. Both
      have become increasingly popular. We shall argue, however, that their use is not
      always safe. If IDI and NRI are used to measure gain in prediction performance,
      then poorly calibrated models may appear advantageous, and in a simulation study,
      even the model that actually generates the data (and hence is the best possible
      model) can be improved on without adding measured information. We illustrate
      these shortcomings in actual cancer data as well as by Monte Carlo simulations.
      In these examples, we contrast IDI and NRI with the area under ROC and the Brier
      score. Unlike IDI and NRI, these traditional measures have the characteristic
      that prognostic performance cannot be accidentally or deliberately inflated.

PMID- 23553437
TI  - Targeting the IL-4/IL-13 signaling pathway sensitizes Hodgkin lymphoma cells to
      chemotherapeutic drugs.
AB  - Hodgkin/Reed-Sternberg lymphoma (HL) is a clonal B-cell-related malignancy.
      Although many patients with HL can be cured by the current regimen of high-dose
      multi-agent chemotherapy, the treatment causes high risks of later pathologies
      including secondary malignancies. This fact highlights the demand to develop
      rational treatment for HL. Survival and growth of HL cells are largely dependent
      on their microenvironment. In this study, using the HL cell lines L1236 and KM-H2
      as model systems, we investigated the role of IL-4/IL-13 signaling in regulation
      of drug sensitivity and resistance in HL. We show that specific blocking of IL-4
      and IL-13-mediated STAT6 activation by either an IL-4-binding fusion protein
      APG598 or an IL-4R antagonist APG201 (R121D/Y124D) renders HL cells more prone to
      apoptotic killing by chemotherapeutic drugs such as Mitomycin C, 5-Fluorouracil,
      Etopside, Doxorubicin and Paclitaxel. This effect is due to inhibition of STAT6
      mediated elevation of expression of the anti-apoptotic Bcl-2 family protein Bcl
      xL. Employing ChIP analysis in combination with APG201 or STAT6-specific siRNA we
      identified a defined STAT6-binding site in the Bcl-xL promoter region from -1967
      to -1957 of the transcription start site. Our data demonstrate that the IL-4/IL
      13-STAT6-Bcl-xL axis may be an important target for HL treatment. This study also
      suggests that combination of classical chemotherapeutic drugs with the IL-4/IL-13
      antagonists may enhance efficacy and reduce risks of toxicity from high dose of
      drugs in HL treatment. 

PMID- 23553438
TI  - Secondary findings from non-invasive prenatal testing for common fetal
      aneuploidies by whole genome sequencing as a clinical service.
AB  - OBJECTIVE: To report secondary or additional findings arising from introduction
      of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing
      as a clinical service. METHODS: Five cases with secondary findings were reviewed.
      RESULTS: In Case 1, NIPT revealed a large duplication in chromosome 18p, which
      was supported by arrayCGH of amniocyte DNA, with final karyotype showing mosaic
      tetrasomy 18p. In Case 2, a deletion in the proximal long arm of chromosome 18 of
      maternal origin was suspected and confirmed by arrayCGH of maternal white cell
      DNA. In Case 3, NIPT was negative for trisomies 21 and 18. In-depth analysis for
      deletions/duplications was requested when fetal structural anomalies were
      detected at routine scan. A deletion in the proximal long arm of chromosome 3 was
      found and confirmed by karyotyping. In Case 4, NIPT correctly predicted confined
      placental mosaicism with triple trisomy involving chromosomes X, 7 and 21. In
      Case 5, NIPT correctly detected a previously unknown maternal mosaicism for 45X.
      CONCLUSION: Non-invasive prenatal testing is able to detect a wide range of
      fetal, placental and maternal chromosomal abnormalities. This has important
      implications on patient counseling when an abnormality is detected by NIPT.

PMID- 23553439
TI  - Long-term detection of human adipose-derived mesenchymal stem cells after
      intraarticular injection in SCID mice.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) represent a promising tool for cell
      therapy for several disorders, among them the osteoarticular diseases. For such
      clinical applications, intraarticular (IA) injection of MSCs may be favored for
      higher levels of safety and targeting of specific joints. Although the safety of
      intravenous (IV) administration of MSCs has been reported in a number of clinical
      trials, the safety and biodistribution of MSCs after IA injection have not been
      tested. Our objective was to assess the toxicity of clinical-grade human adipose
      derived MSCs (AD-MSCs), as well as their biodistribution, after IA injection into
      SCID mice. METHODS: SCID mice received IA or IV administration of 10(6) human AD
      MSCs. Several tissues were recovered at different time points and processed for
      histologic assessment or real-time polymerase chain reaction (PCR) analysis. A
      highly sensitive assay was used to monitor the distribution of AD-MSCs, based on
      amplification of human-specific Alu sequences. RESULTS: Absence of toxicity was
      observed after AD-MSC infusion. Alu PCR assay revealed a high sensitivity (1
      human AD-MSC/10(5) murine cells), with a large linear range (1-5 * 10(4) /10(5)
      murine cells). Importantly, 15% of the IA-injected AD-MSCs were detectable in the
      joint for the first month and 1.5% of the AD-MSCs engrafted over the long term,
      at least 6 months. AD-MSCs were observed in the injected joints and in areas of
      tissue referred to as stem cell niches, such as the bone marrow, adipose tissue,
      and muscle. CONCLUSION: These data support the feasibility and safety of using IA
      delivery of human AD-MSCs in the treatment of rheumatic diseases that affect the
      joints.

PMID- 23553440
TI  - Current classification systems for adult degenerative scoliosis.
AB  - At present, a big effort of the scientific community has been directed toward a
      more proper and standardized approach to the patients affected by degenerative
      scoliosis, and recent attention has turned toward the development of
      classification schemes. A literature analysis highlighted several classification
      schemes developed for degenerative scoliosis patients: the Simmons classification
      system, the Aebi system, the Faldini working classification system, the Schwab
      system, and the Scoliosis Research Society system. Aim of the current manuscript
      is to scrutinize the available literature in order to provide a comprehensive
      overview of these current classification schemes for adult scoliosis, by
      describing and commenting clinical development, limits and potential of their
      application together with their implications for surgical planning.

PMID- 23553441
TI  - Live cell fluorescence imaging for early expression and localization of RIB1 and
      RIB3 genes in Ashbya gossypii.
AB  - Ashbya gossypii is a riboflavin overproducing filamentous fungus. RIB1 and RIB3
      genes encode GTP-cyclohydrolase II (GCH II) and DHBP synthase, respectively, the
      two rate limiting enzymes of the riboflavin biosynthetic pathway. The genes
      encoding yeast enhanced green fluorescent protein (yEGFP) and mCherry were fused
      with RIB1 and RIB3 genes, under their native promoters by PCR-based gene tagging
      method for their early in vivo expression and cellular localization in A.
      gossypii. In the integrative transformants, the fusion proteins were expressed as
      cytoplasmic proteins from the germ bubble stage, in all the cells throughout the
      hypha. This was evident from the observation that mCherry fusion proteins were
      seen outside the vacuoles in the cytoplasm. The older matured cells of 14 h
      hyphae developed large vacuoles which showed green autofluorescence due to
      riboflavin. It is concluded that RIB1 and RIB3 genes are constitutively expressed
      in all the cells of this multicellular multinucleate fungus. 

PMID- 23553442
TI  - Bag-3 expression is involved in pathogenesis and progression of colorectal
      carcinomas.
AB  - Bcl-2-associated athanogene 3 (Bag-3) belongs to a member of the Hsc70 binding co
      chaperone Bag-family proteins and has critical roles in protein homeostasis, cell
      survival, actin organization, cell adhesion, cell motility and tumor metastasis.
      To clarify the role of Bag-3 in colorectal carcinogenesis and subsequent
      development, its expression was examined by immunohistochemistry (IHC) and in
      situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas,
      adenomas, non-neoplastic mucosa (NNM) and metastatic carcinomas in lymph node and
      liver. Colorectal carcinoma tissue and cell lines were studied for Bag-3
      expression by RT-PCR, Western blot and immunofluorescence. The results
      demonstrated that Bag3 was distinctly expressed in Colo201, Colo205, DLD-1, HCT
      15, HCT-116, HT-29, KM-12, SW480, SW620, and WiDr at both mRNA and protein
      levels. Carcinoma showed stronger Bag-3 expression than adjacent NNM by IHC and
      Western blot (P<0.05), while its mRNA had the opposite by real-time PCR and ISH
      (P<0.05). Metastatic carcinoma more frequently expressed Bag-3 mRNA in lymph node
      and liver than in primary carcinoma (P<0.05). Immunohistochemically, Bag-3
      expression was seen to gradually decrease from carcinoma, adenoma to NNM
      (P<0.05). There was a positive correlation between Bag-3 expression and TNM
      staging and GRP94 expression (P<0.05), but no relationship to patient age or sex,
      tumor size, depth of invasion, lymphatic or venous invasion, lymph node
      metastasis, differentiation or prognosis of colorectal carcinomas (P<0.05). Our
      study indicated that aberrant Bag-3 expression might be involved in colorectal
      adenoma-adenocarcinoma sequence and subsequent progression.

PMID- 23553443
TI  - Haplotype dictionary for the Rht-1 loci in wheat.
AB  - The introduction of Reduced height (Rht)-B1b and Rht-D1b into bread wheat
      (Triticum aestivum) varieties was a key component of the 'green revolution' and
      today these alleles are the primary sources of semi-dwarfism in wheat. The Rht-1
      loci encode DELLA proteins, which are transcription factors that affect plant
      growth and stress tolerance. In bread wheat, Rht-D1b and Rht-B1b influence
      resistance to the disease Fusarium Head Blight. To identify Rht-1 variants, locus
      specific primers were developed and used to sequence the entire open reading
      frame (ORF) and 1.7 kb of the 5' and 0.5 kb of the 3' flanking regions of Rht-A1
      (Rht-A1+f), Rht-B1 (Rht-B1+f), and Rht-D1 (Rht-D1+f) in bread wheat (36 sequences
      from each genome) and tetraploid and diploid wheat (TDW) (one to three sequences
      from each genome). Among the bread wheat accessions, the Rht-A1+f and Rht-D1+f
      sequences contained relatively low genetic diversity and few haplotypes relative
      to the Rht-B1+f sequences. The TDW accessions were relatively rich in genetic
      diversity and contained the majority of the polymorphic sites. Novel
      polymorphisms, relative to 'Chinese Spring', discovered among the accessions
      include 160 and 197 bp insertions 5' of Rht-B1 and a frameshift in the Rht-B1
      ORF. Quantitative real-time PCR using shoot and leaf tissue from 5-day-old
      seedlings of genotypes lacking or containing the 5' insertions revealed no major
      effect on Rht-B1 transcript accumulation. This research provides insights into
      the genetic diversity present at the Rht-1 loci in modern bread wheat and in
      relation to ancestral wheat accessions. 

PMID- 23553445
TI  - The band structure of WO3 and non-rigid-band behaviour in Na0.67WO3 derived from
      soft x-ray spectroscopy and density functional theory.
AB  - The electronic structure of single-crystal WO3 and Na0.67WO3 (a sodium-tungsten
      bronze) has been measured using soft x-ray absorption and resonant soft x-ray
      emission oxygen K-edge spectroscopies. The spectral features show clear
      differences in energy and intensity between WO3 and Na0.67WO3. The x-ray emission
      spectrum of metallic Na0.67WO3 terminates in a distinct Fermi edge. The rigid
      band model fails to explain the electronic structure of Na0.67WO3 in terms of a
      simple addition of electrons to the conduction band of WO3. Instead, Na bonding
      and Na 3s-O 2p hybridization need to be considered for the sodium-tungsten
      bronze, along with occupation of the bottom of the conduction band. Furthermore,
      the anisotropy in the band structure of monoclinic gamma-WO3 revealed by the
      experimental spectra with orbital-resolved geometry is explained via density
      functional theory calculations. For gamma-WO3 itself, good agreement is found
      between the experimental O K-edge spectra and the theoretical partial density of
      states of O 2p orbitals. Indirect and direct bandgaps of insulating WO3 are
      determined from extrapolating separations between spectral leading edges and
      accounting for the core-hole energy shift in the absorption process. The O 2p non
      bonding states show upward band dispersion as a function of incident photon
      energy for both compounds, which is explained using the calculated band structure
      and experimental geometry.

PMID- 23553444
TI  - Discrimination and psychological distress among recently released male prisoners.
AB  - Though theoretical perspectives suggest experiences of stigma and discrimination
      after release may be one pathway through which incarceration leads to poor mental
      health, little research considers the relationship between discrimination and
      mental health among former inmates. In this article, data from a sample of men
      recently released from prison to Oakland or San Francisco, California (N = 172),
      are used to consider how criminal record discrimination and racial/ethnic
      discrimination are independently and cumulatively associated with psychological
      distress. Results indicate that (a) the frequency of criminal record
      discrimination and racial/ethnic discrimination are similar; (b) both forms of
      discrimination are independently, negatively associated with psychological
      distress; and (c) the level of racial/ethnic discrimination does not alter the
      association between criminal record discrimination and psychological distress.
      The results highlight that criminal record discrimination is an important social
      stressor with negative implications for the mental health of previously
      incarcerated individuals. 

PMID- 23553446
TI  - Antipsychotics and torsadogenic risk: signals emerging from the US FDA Adverse
      Event Reporting System database.
AB  - BACKGROUND: Drug-induced torsades de pointes (TdP) and related clinical entities
      represent a current regulatory and clinical burden. OBJECTIVE: As part of the FP7
      ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly
      available US FDA Adverse Event Reporting System (FAERS) database to detect
      signals of torsadogenicity for antipsychotics (APs). METHODS: Four groups of
      events in decreasing order of drug-attributable risk were identified: (1) TdP,
      (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4)
      sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence
      interval (CI) was calculated through a cumulative analysis from group 1 to 4. For
      groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g.,
      antiarrhythmics) and stratified for AZCERT drugs, lists I and II
      (http://www.azcert.org , as of June 2011). A potential signal of torsadogenicity
      was defined if a drug met all the following criteria: (a) four or more cases in
      group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative
      approach; (c) significant adjusted ROR for group 1+2 in the stratum without
      AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). RESULTS: Over
      the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group
      1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria,
      the following potential signals of torsadogenicity were found: amisulpride (25
      cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82
      84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45
      9.30). CONCLUSIONS: This pharmacovigilance analysis on the FAERS found 3
      potential signals of torsadogenicity for drugs previously unknown for this risk.

PMID- 23553447
TI  - Development and Initial Validation of a Patient-Reported Adverse Drug Event
      Questionnaire.
AB  - BACKGROUND: Direct patient reporting of adverse drug events (ADEs) is relevant
      for the evaluation of drug safety. To collect such data in clinical trials and
      postmarketing studies, a valid questionnaire is needed that can measure all
      possible ADEs experienced by patients. OBJECTIVE: Our aim was to develop and test
      a generic questionnaire to identify ADEs and quantify their nature and causality
      as reported by patients. METHODS: We created a draft list of common ADEs in lay
      terms, which were classified in body categories and mapped to the Medical
      Dictionary for Regulatory Activities (MedDRA((r))) terminology. Questions about
      the nature and causality were derived from existing questionnaires and causality
      scales. Content validity was tested through cognitive debriefing, revising the
      questionnaire in an iterative process. Feasibility and reliability were assessed
      using a Web-based version of the questionnaire. Patients received the
      questionnaire twice. Feasibility was assessed by the reported time needed for
      completion and ease of use. Reliability was calculated using Cohen's kappa and
      proportion of positive agreement (PPA) on: (1) any ADE at patient level; (2)
      similar ADEs at MedDRA((r)) System Organ Class level; and (3) the same ADE at ADE
      specific level. RESULTS: In the development phase, 28 patients with type 2
      diabetes or asthma/chronic obstructive pulmonary disease (COPD) participated.
      Questions and answer options were rephrased, layout was improved, and changes
      were made in the classification of ADEs. The final questionnaire consisted of 252
      ADEs organized in 16 body categories, and included 14 questions per reported ADE.
      A total of 135 patients using a median of five different drugs completed the Web
      based questionnaire twice. The median completion time was 15 min for patients not
      reporting any ADE, and 30 min for patients reporting at least one ADE. Three
      quarters of the patients found the questionnaire easy to use. Test-retest
      reliability was acceptable at patient level (kappa = 0.50, PPA 0.64) and at
      MedDRA((r)) System Organ Class level (kappa = 0.52, PPA 0.54), but was low at ADE
      specific level (kappa = 0.38, PPA 0.38). CONCLUSION: We developed a generic
      patient-reported ADE questionnaire and confirmed its content validity. The
      questionnaire was feasible and reliable for reporting any ADE and similar ADEs at
      MedDRA((r)) System Organ Class level. Additional work is, however, needed to
      reliably quantify specific ADEs reported by patients.

PMID- 23553448
TI  - Results from the first decade of research conducted by the Research on Adverse
      Drug Events and Reports (RADAR) project.
AB  - INTRODUCTION: In 1998, a multidisciplinary team of investigators initiated the
      Research on Adverse Drug events And Reports (RADAR) project, a post-marketing
      surveillance effort that systematically investigates and disseminates information
      describing serious and previously unrecognized serious adverse drug and device
      reactions (sADRs). OBJECTIVE: Herein, we describe the findings, dissemination
      efforts, and lessons learned from the first decade of the RADAR project. METHODS:
      After identifying serious and unexpected clinical events suitable for further
      investigation, RADAR collaborators derived case information from physician
      queries, published and unpublished clinical trials, case reports, US FDA
      databases and manufacturer sales figures. STUDY SELECTION: All major RADAR
      publications from 1998 to the present are included in this analysis. DATA
      EXTRACTION: For each RADAR publication, data were abstracted on data source,
      correlative basic science findings, dissemination and resultant safety
      information. RESULTS: RADAR investigators reported 43 serious ADRs. Data sources
      included case reports (17 sADRs), registries (5 sADRs), referral centers (8
      sADRs) and clinical trial reports (13 sADRs). Correlative basic science findings
      were reported for ten sADRs. Thirty-seven sADRS were described as published case
      reports (5 sADRs) or published case-series (32 sADRs). Related safety information
      was disseminated as warnings or boxed warnings in the package insert (17 sADRs)
      and/or 'Dear Healthcare Professional' letters (14 sADRs). CONCLUSION: An
      independent National Institutes of Health-funded post-marketing surveillance
      programme can supplement existing regulatory and pharmaceutical manufacturer
      supported drug safety initiatives.

PMID- 23553449
TI  - Evaluation of a teaching tool to increase the accuracy of pilot balloon palpation
      for measuring tracheostomy tube cuff pressure.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to evaluate the efficacy of
      a novel teaching tool to improve health care providers' ability to inflate
      tracheostomy tube cuffs to the appropriate pressure. STUDY DESIGN: Single
      blinded, randomized, controlled trial. METHODS: Subjects were randomized to a
      control and study group. The control group viewed a video about inflating
      tracheostomy tube cuffs to safe pressure levels. The study group viewed the same
      video and also got to palpate the pilot balloons of tracheostomy tube cuffs
      inflated to three different pressures. All subjects inflated tracheostomy tube
      cuffs to pressures they believed to be appropriate based on palpation of the
      pilot balloon preintervention, and immediately, 2 weeks, and 3 months
      postintervention. RESULTS: Forty-nine health care providers participated in the
      study. There was no significant difference in the mean preintervention cuff
      inflation pressures between the two groups (36 cm H2 O vs. 38 cm H2 O, P =
      0.4888), with both initially overinflating. Postintervention, the study group
      inflated the cuffs to significantly lower pressures than the control group,
      closer to the ideal of 25 cm H2 O (26 cm H2 O vs. 35 cm H2 O, P = 0.0001). This
      difference was also observed 2 weeks (28 cm H2 O vs. 37 cm H2 O P <0.0001) and 3
      months (28 cm H2 O vs. 36 cm H2 O, P = 0.0002) postintervention. CONCLUSIONS: The
      novel teaching tool evaluated in this study is simple, easily reproducible, and
      low-cost. Its use leads to long-lasting improvement in health care providers'
      ability to more accurately inflate tracheostomy tube cuffs to safe pressures.

PMID- 23553450
TI  - Prediction models in Lynch syndrome.
AB  - Prediction models for the identification of Lynch syndrome have been developed to
      quantify an individual's risk of carrying a mismatch repair gene mutation and
      help clinicians decide for whom further risk assessment and genetic testing is
      necessary. There are diverse clinical settings in which a healthcare provider has
      the opportunity to assess an individual for Lynch syndrome. Prediction models
      offer a potentially feasible and useful strategy to systematically identify at
      risk individuals, whether they are affected with colorectal cancer or not, and to
      help with management of the implications of molecular and germline test results.
      Given the complexity of diagnostic information currently available to clinicians
      involved in identifying and caring for patients with Lynch syndrome, prediction
      models provide a useful and complementary aid in medical decision-making.
      Systematic implementation of prediction models estimates should be considered in
      routine clinical care and at various stages of cancer risk assessment and
      prevention. In this manuscript, we review the main prediction models developed
      for Lynch syndrome, focus on their specific features and performance assessed in
      several validation studies, compare the models with other clinical and molecular
      strategies for the diagnosis of Lynch syndrome, and discuss their potential uses
      in clinical practice. 

PMID- 23553451
TI  - Recombination within the apospory specific genomic region leads to the uncoupling
      of apomixis components in Cenchrus ciliaris.
AB  - Apomixis enables the clonal propagation of maternal genotypes through seed. If
      apomixis could be harnessed via genetic engineering or introgression, it would
      have a major economic impact for agricultural crops. In the grass species
      Pennisetum squamulatum and Cenchrus ciliaris (syn. P. ciliare), apomixis is
      controlled by a single dominant "locus", the apospory-specific genomic region
      (ASGR). For P. squamulatum, 18 published sequenced characterized amplified region
      (SCAR) markers have been identified which always co-segregate with apospory. Six
      of these markers are conserved SCARs in the closely related species, C. ciliaris
      and co-segregate with the trait. A screen of progeny from a cross of sexual *
      apomictic C. ciliaris genotypes identified a plant, A8, retaining two of the six
      ASGR-linked SCAR markers. Additional and newly identified ASGR-linked markers
      were generated to help identify the extent of recombination within the ASGR.
      Based on analysis of missing markers, the A8 recombinant plant has lost a
      significant portion of the ASGR but continues to form aposporous embryo sacs.
      Seedlings produced from aposporous embryo sacs are 6* in ploidy level and hence
      the A8 recombinant does not express parthenogenesis. The recombinant A8 plant
      represents a step forward in reducing the complexity of the ASGR locus to
      determine the factor(s) required for aposporous embryo sac formation and
      documents the separation of expression of the two components of apomixis in C.
      ciliaris. 

PMID- 23553452
TI  - Sequence analysis of the whole genome of a recombinant Marek's disease virus
      strain, GX0101, with a reticuloendotheliosis virus LTR insert.
AB  - Marek's disease virus Chinese strain GX0101, isolated in 2001, is the first
      reported recombinant gallid herpesvirus type 2 (GaHV-2) field strain with one
      reticuloendotheliosis virus (REV) long terminal repeat (LTR) insert. We
      constructed an infectious bacterial artificial chromosome (BAC) clone of GX0101,
      which showed characteristics very similar to those of the parental virus in
      replication and pathogenicity. Using the GX0101 BAC clone, the complete genome of
      GX0101 was sequenced and analyzed. The length of the GX0101 genome is 178,101 bp,
      and it contains only one REV-LTR insert at a site 267 bp upstream of the sorf2
      gene. 

PMID- 23553453
TI  - Identification and complete genome analysis of a virus variant or putative new
      foveavirus associated with apple green crinkle disease.
AB  - A virus identified as "apple green crinkle associated virus" (AGCaV) was isolated
      from Aurora Golden Gala apple showing severe symptoms of green crinkle disease.
      Evidence was obtained of a potential causal relationship to the disease. The
      viral genome consists of 9266 nucleotides, excluding the poly(A) tail at the 3'
      terminus. It has a genome organization similar to that of members of the species
      Apple stem pitting virus (ASPV), the type species of the genus Foveavirus, family
      Betaflexiviridae. ORF1 of AGCaV encodes a replicase-complex polyprotein with a
      molecular mass of 247 kDa; the proteins of ORFs 2, 3, and 4 (TGB proteins) are
      estimated to be 25.1 kDa, 12.8 kDa, and 7.4 kDa, respectively; and ORF5 encodes
      the CP, with an estimated molecular mass of 43.3 kDa. Interestingly, AGCaV
      utilizes different stop codons for ORF1, ORF3, and ORF5 compared to the ASPV type
      isolate PA66, and between the two viruses, six distinct indel events were
      observed within ORF5. AGCaV has four non-coding regions (NCRs), including a 5'
      NCR (60 nt), a 3'-NCR (134 nt), and two intergenic (IG) NCRs: IG-NCR1 (69 nt) and
      IG-NCR2 (91 nt). A conserved stable hairpin structure was identified in the
      variable 5'-NCR of members of the genus Foveavirus. AGCaV may be a variant or
      strain of ASPV with unique biological properties, but there is evidence that it
      may be a distinct putative foveavirus. 

PMID- 23553455
TI  - Large-scale codon de-optimisation of the p29 replicase gene by synonymous
      substitutions causes a loss of infectivity of melon necrotic spot virus.
AB  - The effect of synonymous substitutions in the melon necrotic spot virus p29
      replicase gene on viral pathogenicity was investigated. The codons in the p29
      gene were replaced by the least frequently used synonymous codons in Arabidopsis
      thaliana or melons. Mechanical inoculation of melon with p29 variants resulted in
      a loss of viral infectivity when all, one-half, or one-quarter of the gene was de
      optimised. The effect of the de-optimisation in one-sixth of the gene was
      different depending on the de-optimised region. These results demonstrate that
      large-scale codon bias de-optimisation without amino acid substitutions of the
      p29 gene alter viral infectivity. 

PMID- 23553454
TI  - Prevalence of hepatitis B virus and hepatitis C virus in patients with human
      immunodeficiency virus infection in Central China.
AB  - Co-infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with human
      immunodeficiency virus (HIV) has an adverse effect on liver disease progression.
      This study investigated the prevalence of HBV and/or HCV co-infection in HIV
      infected patients in Central China. A total of 978 HIV-infected patients from
      Hunan Province were enrolled. HBV serum markers, anti-hepatitis-C-virus antibody
      (anti-HCV), HBV DNA, and HBV genotypes were analyzed. The prevalence of hepatitis
      B surface antigen (HBsAg) and anti-HCV in HIV-infected patients was 19.4 % and
      62.4 %, respectively. The prevalence of anti-HCV in HIV-positive intravenous drug
      users was 93.6 %. Among HBsAg-positive patients, 88.1 % were found to have at
      least one HBV serum marker. The rates of HIV mono-infection, HBV/HIV dual
      infection, HCV/HIV dual infection, and HBV/HCV/HIV triple infection were 30.4 %,
      7.2 %, 50.2 %, and 12.2 %, respectively. Antibody to HBsAg (Anti-HBs) was more
      common in anti-HCV-positive than anti-HCV-negative patients (53.3 % vs 40.2 %, P
      = 0.000), but isolated hepatitis B core antibody (anti-HBc) was more common in
      anti-HCV-negative than anti-HCV-positive patients (24.2 % vs 12.3 %, P = 0.000).
      Hepatitis B e antigen (HBeAg) and sexual transmission were independent risk
      factors for active HBV replication. Intravenous drug use and male sex were
      independent risk factors, but old age and presence of HBeAg were independent
      protective factors for anti-HCV. Co-infection of HBV and/or HCV with HIV
      infection is common in central China. HCV status is associated with anti-HBs and
      isolated anti-HBc in co-infected patients. 

PMID- 23553456
TI  - The role of oligomerization for the biological functions of the arenavirus
      nucleoprotein.
AB  - The Lassa virus nucleoprotein (NP) is a multifunctional protein that plays an
      essential role in many aspects of the viral life cycle, including RNA
      encapsidation, viral transcription and replication, recruitment of
      ribonucleoprotein complexes to viral budding sites, and inhibition of the host
      cell interferon response. While it is known that NP is capable of forming
      oligomers, both the oligomeric state of NP in mammalian cells and the
      significance of NP oligomerization for its various functions remain unclear.
      Here, we demonstrate that Lassa virus NP solely forms trimers upon expression in
      mammalian cells. Using a minigenome assay we show that mutants that are not able
      to form stable trimers are no longer functional during transcription and/or
      replication of the minigenome, indicating that NP trimerization is essential for
      transcription and/or replication of the viral genome. However, mutations leading
      to destabilization of the NP trimer did not impact the incorporation of NP into
      virus-like particles or its ability to suppress interferon-induced gene
      expression, two important functions of arenavirus NP. 

PMID- 23553457
TI  - Complete nucleotide sequence of rose yellow mosaic virus, a novel member of the
      family Potyviridae.
AB  - The complete genomic sequence of rose yellow mosaic virus (RoYMV) was determined
      and found to have all the features that are characteristic of members of the
      family Potyviridae. The RoYMV genome is 9508 nucleotides long excluding the 3'
      poly-(A) tail and contains a single open reading frame encoding a polyprotein of
      3067 amino acids. The RoYMV P3 and CI cistrons are shorter than those of other
      members of the family Potyviridae, and the 6K1 cistron is completely absent.
      Comparative sequence analysis revealed that RoYMV had highest amino acid sequence
      identity across the entire genome sequence to brome streak mosaic virus (33 %)
      and to turnip mosaic virus (30 %) at the coat protein level. Based on its low
      sequence similarity to known members of the family Potyviridae and phylogenetic
      analysis, RoYMV appears to be a distinct, previously undescribed, member of this
      family. 

PMID- 23553459
TI  - Composite pH predicts esomeprazole response in laryngopharyngeal reflux without
      typical reflux syndrome.
AB  - OBJECTIVES/HYPOTHESIS: Factors predicting the efficacy of proton pump inhibitors
      (PPIs) in patients with suspected laryngopharyngeal reflux (LPR) are unclear. PPI
      treatment in patients without concomitant esophageal syndrome remains
      controversial. We investigated whether composite pH can predict PPI treatment
      response for LPR with or without concomitant typical reflux syndrome (CTRS).
      STUDY DESIGN: Prospective, open-label therapeutic cohort study. METHODS: Patients
      with LPR in a tertiary center divided by presence (n = 65) and absence (n = 42)
      of CTRS underwent 24-hour esophagopharyngeal pH test and took esomeprazole (40
      mg, twice daily) for 12 weeks. Positive composite pH was defined as the presence
      of 1) excessive pharyngeal acid reflux, and/or 2) excessive distal esophageal
      acid reflux. A responder was defined as a patient with >=50% reduction in primary
      laryngeal symptoms. The change in reflux symptoms was determined using the reflux
      symptom index (RSI) questionnaire. Logistic regression and mixed model were used
      to evaluate the predictability of the composite pH parameter. RESULTS: After 8
      and 12 weeks of treatment, participants with positive composite pH were 10.3-fold
      (95% confidence interval [CI], 1.7-61.5; P = .01) and 7.9-fold (95% CI, 1.4-44.8;
      P = .02) more likely to respond, respectively, than participants with negative
      composite pH among patients without CTRS. However, no difference was found in
      those with CTRS. Weekly repeated measures of RSI yielded similar findings.
      CONCLUSIONS: In patients with suspected LPR without CTRS, a composite pH
      parameter, which incorporates pharyngeal and distal esophageal acid reflux, may
      predict response to esomeprazole therapy.

PMID- 23553458
TI  - Analysis of sequences of hepatitis C virus NS5A genotype 1 in HIV-coinfected
      patients with a null response to nitazoxanide or peg-interferon plus ribavirin.
AB  - Even though new drugs have been approved for treatment of hepatitis C virus (HCV)
      infection, the risk of drug-drug interactions and concern about overlapping
      toxicities has hindered the development of studies in HIV/HCV-coinfected
      individuals. Traditional treatment with pegylated interferon plus ribavirin (peg
      IFN + RBV) is very expensive and has a low rate of sustained virological response
      in coinfected patients, especially if they are infected with HCV genotype 1.
      Nitazoxanide (NTZ) is a drug that is being evaluated for the treatment of chronic
      HCV infection, both in HCV-monoinfected and HIV/HCV-coinfected patients.
      Understanding the NTZ resistance mechanism could allow the development of
      resistance to be minimized and would expand the treatment options, mainly in
      special populations such as HIV/HCV-coinfected patients. Similarly to IFN, NTZ
      increases the activity of the cellular protein kinase activated by double
      stranded RNA (PKR), a key kinase in the innate antiviral response. In order to
      elucidate whether sequence heterogeneity in the PKR-binding domain of HCV NS5A
      genotype 1 could influence the antiviral activity of either NTZ monotherapy or
      peg-IFN + RBV, baseline and end-of-therapy plasma samples from two groups of
      eleven non-responder HIV/HCV-coinfected patients that had received NTZ or peg-IFN
      + RBV were studied. Most of the HCV NS5A sequences examined at the end of therapy
      did not change from the baseline, even after 30 days course of antiviral therapy.
      An extensive comparison of HCV NS5A genotype 1 and 4 sequences from the database
      with reported IFN therapy outcome was performed in order to infer their
      phylogenetic relationships. The HCV genotype 1 NS5A nucleotide sequences from
      therapy-non-responder patients were intermingled amongst those from the database,
      irrespective of their IFN-therapy outcome. When comparing NS5A-PKRBD amino acid
      sequences, significant differences were observed in genotype 4, but not in
      genotype 1 (p < 0.0001 and p > 0.05, respectively). In conclusion, despite IFN
      and NTZ sharing the protein kinase activated by double-stranded RNA as their
      cellular target, the HCV genotype 1 strategy to counteract the IFN action
      mediated by NS5A ISDR/PKRBD does not explain drug resistance in HIV/HCV
      coinfected patients. Other viral factors that are possibly involved are discussed
      as well. 

PMID- 23553460
TI  - Bioactive lipids in the butter production chain from Parmigiano Reggiano cheese
      area.
AB  - BACKGROUND: Bovine milk contains hundreds of diverse components, including
      proteins, peptides, amino acids, lipids, lactose, vitamins and minerals.
      Specifically, the lipid composition is influenced by different variables such as
      breed, feed and technological process. In this study the fatty acid and
      phospholipid compositions of different samples of butter and its by-products from
      the Parmigiano Reggiano cheese area, produced by industrial and traditional
      churning processes, were determined. RESULTS: The fatty acid composition of
      samples manufactured by the traditional method showed higher levels of
      monounsaturated and polyunsaturated fatty acids compared with industrial samples.
      In particular, the contents of n-3 fatty acids and conjugated linoleic acids were
      higher in samples produced by the traditional method than in samples produced
      industrially. Sample phospholipid composition also varied between the two
      technological processes. Phosphatidylethanolamine was the major phospholipid in
      cream, butter and buttermilk samples obtained by the industrial process as well
      as in cream and buttermilk samples from the traditional process, while
      phosphatidylcholine was the major phospholipid in traditionally produced butter.
      This result may be explained by the different churning processes causing
      different types of membrane disruption. Generally, samples produced traditionally
      had higher contents of total phospholipids; in particular, butter produced by the
      traditional method had a total phospholipid content 33% higher than that of
      industrially produced butter. CONCLUSION: The samples studied represent the two
      types of products present in the Parmigiano Reggiano cheese area, where the
      industrial churning process is widespread compared with the traditional
      processing of Reggiana cow's milk. This is because Reggiana cow's milk production
      is lower than that of other breeds and the traditional churning process is time
      consuming and economically disadvantageous. However, its products have been
      demonstrated to contain more bioactive lipids compared with products obtained
      from other breeds and by the industrial process.

PMID- 23553462
TI  - Effects of oxytocin on women's aggression depend on state anxiety.
AB  - Research on oxytocin (OT) indicates that it has stress reducing effects. This
      leads to opposing predictions of decreased and increased aggression which we
      examine in this study. Following completion of a state anxiety measure and
      administration of OT or a placebo, female participants took part in a competitive
      aggression game (PSAP) for a monetary prize which, if won, would be paid to a
      loved one. In the game, three options were available: participants could earn
      points; attack their opponent by deducting points; and defend themselves against
      point deduction by their opponent. There was no main effect of OT on these
      responses, however there was an interaction with state anxiety. In the placebo
      condition, women higher in state anxiety showed a significantly higher ratio of
      Attack-to-Earn responses than low anxiety women. Under oxytocin, there was a
      significant reduction in their Attack:Earn ratio resulting in no significant
      difference between high and low state anxiety groups. There was a similar trend
      for the Defend:Earn ratio. The reduction of reactive aggression in state anxious
      women supports the view that OT may decrease negative behavior and increase
      constructive behavior even under conditions of provocation.

PMID- 23553461
TI  - Global asymptotic stability and the ideal free distribution in a starvation
      driven diffusion.
AB  - We study a logistic model with a nonlinear random diffusion in a Fokker-Planck
      type law, but not in Fick's law. In the model individuals are assumed to increase
      their motility if they starve. Any directional information to resource is not
      assumed in this starvation driven diffusion and individuals disperse in a random
      walk style strategy. However, the non-uniformity in the motility produces an
      advection toward surplus resource. Several basic properties of the model are
      obtained including the global asymptotic stability and the acquisition of the
      ideal free distribution. 

PMID- 23553463
TI  - Bilateral modified nasoseptal "rescue" flaps in the endoscopic endonasal
      transsphenoidal approach.
AB  - OBJECTIVES/HYPOTHESIS: For a wide exposure of skull base and preservation of
      septal mucosa, we have raised bilateral modified nasoseptal rescue flaps in the
      endoscopic endonasal transsphenoidal approach (EETSA) and evaluated the
      usefulness of these flaps elevation. STUDY DESIGN: Case series. METHODS: The
      study population comprised the patients who underwent EETSA with bilateral
      modified nasoseptal rescue flaps elevation between February 2009 and June 2012.
      We retrospectively reviewed patients' medical records. Patients underwent
      preoperative nasal evaluation using the Nasal Obstruction Symptom Evaluation
      (NOSE), Sino-Nasal Outcome Test (SNOT-20), and a visual analogue scale (VAS) to
      assess several nasal symptoms. Repeat testing was performed 6 months
      postoperatively. RESULTS: A total of 92 patients underwent the EETSA with
      bilateral modified nasoseptal rescue flaps elevation. A total of 17 patients had
      intraoperative cerebrospinal fluid (CSF) leakage. Three patients underwent
      extension of the modified nasoseptal rescue flap to a conventional nasoseptal
      flap. No patients underwent reoperation due to CSF leakage. There was no
      statistical difference between preoperative and postoperative total SNOT-20 and
      NOSE scores. According to the VAS, subjective olfaction function statistically
      worsened (P = 0.011) postoperatively. CONCLUSION: Bilateral modified nasoseptal
      rescue flaps elevation provided good exposure of the sellar floor, preserved the
      septal branch of sphenopalatine artery, and facilitated removal of sellar tumors.
      We could also preserve more septal mucosa by designing a novel incision and
      repositioning unused flaps to their original sites. Postoperative complications
      of the nasal cavity were thus minimized. We believe that this flap is very useful
      in a variety of settings during the EETSA.

PMID- 23553464
TI  - Role of the pharmacist in achieving performance measures to improve the
      prevention and treatment of venous thromboembolism.
AB  - Current prescribing practices for venous thromboembolism (VTE) prophylaxis and
      treatment are suboptimal, particularly regarding the use of appropriate
      prophylaxis in accordance with evidence-based guidelines. Failure to prevent
      avoidable VTE is associated with a substantial clinical and economic burden, due
      not only to the initial event, but also to VTE recurrence and long-term sequelae.
      Quality improvement initiatives such as the Surgical Care Improvement Project,
      the Centers for Medicare and Medicaid Services, the National Quality Forum, and
      The Joint Commission have developed performance measures to address the shortfall
      and improve adherence with best-practice recommendations. Several studies have
      highlighted the benefits of pharmacist-led anticoagulation services for reducing
      the occurrence of VTE and bleeding complications while reducing excess
      hospitalization and health care costs. By assuming responsibility for
      anticoagulation management, pharmacists can ensure that at-risk patients receive
      the correct drug at the correct dose for the correct duration, from initial
      presentation to outpatient follow-up. Increasing continuity of care in this
      manner will ultimately improve patient outcomes and reduce costs. Pharmacists can
      also play a key role in helping hospitals achieve performance measures by aiding
      in the development and implementation of local VTE guidelines, policies, and
      other quality improvement initiatives; by helping to establish critical pathways
      with protocols; and by providing valuable education for other health care
      professionals and patients alike. Pharmacists are in an ideal position to
      facilitate achievement of VTE-related performance measures and can thus
      substantially contribute to the much-needed improvement in current VTE prevention
      and care.

PMID- 23553465
TI  - Hemorrhagic and serous-filled vesicles and bullae. Fracture blisters.

PMID- 23553466
TI  - Accurate confidence limits for stratified clinical trials.
AB  - For stratified 2 * 2 tables, standard approximate confidence limits can perform
      poorly from a strict frequentist perspective, even for moderate-sized samples,
      yet they are routinely used. In this paper, I show how to use importance sampling
      to compute highly accurate limits in reasonable time. The methodology is very
      general and simple to implement, and orders of magnitude are faster than existing
      alternatives.

PMID- 23553467
TI  - Multidimensional analysis of fetal posterior fossa in health and disease.
AB  - Fetal magnetic resonance imaging (MRI) is now routinely used to further
      investigate cerebellar malformations detected with ultrasound. However, the lack
      of 2D and 3D biometrics in the current literature hinders the detailed
      characterisation and classification of cerebellar anomalies. The main objectives
      of this fetal neuroimaging study were to provide normal posterior fossa growth
      trajectories during the second and third trimesters of pregnancy via semi
      automatic segmentation of reconstructed fetal brain MR images and to assess
      common cerebellar malformations in comparison with the reference data. Using a
      1.5-T MRI scanner, 143 MR images were obtained from 79 normal control and 53
      fetuses with posterior fossa abnormalities that were grouped according to the
      severity of diagnosis on visual MRI inspections. All quantifications were
      performed on volumetric datasets, and supplemental outcome information was
      collected from the surviving infants. Normal growth trajectories of total brain,
      cerebellar, vermis, pons and fourth ventricle volumes showed significant
      correlations with 2D measurements and increased in second-order polynomial trends
      across gestation (Pearson r, p < 0.05). Comparison of normal controls to five
      abnormal cerebellum subgroups depicted significant alterations in volumes that
      could not be detected exclusively with 2D analysis (MANCOVA, p < 0.05). There
      were 15 terminations of pregnancy, 8 neonatal deaths, and a spectrum of genetic
      and neurodevelopmental outcomes in the assessed 24 children with cerebellar
      abnormalities. The given posterior fossa biometrics enhance the delineation of
      normal and abnormal cerebellar phenotypes on fetal MRI and confirm the advantages
      of utilizing advanced neuroimaging tools in clinical fetal research. 

PMID- 23553468
TI  - Intrinsic connectivity networks within cerebellum and beyond in eating disorders.
AB  - Cerebellum seems to have a role both in feeding behavior and emotion regulation;
      therefore, it is a region that warrants further neuroimaging studies in eating
      disorders, severe conditions that determine a significant impairment in the
      physical and psychological domain. The aim of this study was to examine the
      cerebellum intrinsic connectivity during functional magnetic resonance imaging
      resting state in anorexia nervosa (AN), bulimia nervosa (BN), and healthy
      controls (CN). Resting state brain activity was decomposed into intrinsic
      connectivity networks (ICNs) using group spatial independent component analysis
      on the resting blood oxygenation level dependent time courses of 12 AN, 12 BN,
      and 10 CN. We extracted the cerebellar ICN and compared it between groups.
      Intrinsic connectivity within the cerebellar network showed some common
      alterations in eating disordered compared to healthy subjects (e.g., a greater
      connectivity with insulae, vermis, and paravermis and a lesser connectivity with
      parietal lobe); AN and BN patients were characterized by some peculiar
      alterations in connectivity patterns (e.g., greater connectivity with the insulae
      in AN compared to BN, greater connectivity with anterior cingulate cortex in BN
      compared to AN). Our data are consistent with the presence of different
      alterations in the cerebellar network in AN and BN patients that could be related
      to psychopathologic dimensions of eating disorders. 

PMID- 23553470
TI  - Cell-free fetal DNA sex determination identified a maternal SRY gene with a known
      X chromosome deletion.

PMID- 23553469
TI  - From gut changes to type 2 diabetes remission after gastric bypass surgeries.
AB  - Increasing evidence suggests that the gut may influence the host's metabolism and
      ultimately change the outcomes of type 2 diabetes mellitus (T2DM). We review the
      evidence on the relationship between the gut and T2DM remission after gastric
      bypass surgery, and discuss the potential mechanisms underlying the above
      relationship: gut anatomical rearrangement, microbial composition changes,
      altered gut cells, and gut hormone modulation. However, the exact changes and
      their relative importance in the metabolic improvements after gastric bypass
      surgery remain to be further clarified. Elucidating the precise metabolic
      mechanisms of T2DM resolution after bypass surgery will help to reveal the
      molecular mechanisms of pathogenesis, and facilitate the development of novel
      diagnoses and preventative interventions for this common disease.

PMID- 23553471
TI  - Squamous cell carcinoma of the temporal bone: outcomes of radical surgery and
      postoperative radiotherapy.
AB  - OBJECTIVES/HYPOTHESIS: To analyze the treatment outcomes for squamous cell
      carcinoma (SCC) of the temporal bone and to identify factors that may influence
      prognosis. STUDY DESIGN: Retrospective case series. METHODS: Case notes review of
      patients with histologically proven SCC of the temporal bone who had treatment
      with a curative intent at a tertiary referral center in the Northwest of England,
      United Kingdom. RESULTS: A total of 35 patients were treated in this unit over a
      12-year period. The most common presentation was otorrhoea, which was present in
      all patients, followed by otalgia (66%), bleeding (54%), and facial palsy (46%).
      The overall survival for this series was 48.6%. There were four patients with
      stage I tumor, and one case each of stage II and stage III disease. The disease
      free survival for patients with stage I to stage III disease in this series was
      100%. The remaining 29 patients (84%) had stage IV disease, with an overall
      survival in this group of 41.4%. The average survival period of the 18 patients
      who succumbed to local disease was 9.2 months (range 3-22). Poorly differentiated
      SCC was associated with significantly poorer survival (P < 0.05) when compared to
      well and moderately differentiated SCC. Parotid involvement of SCC, node-positive
      neck, and the presence of preoperative facial palsy was not associated with
      poorer survival outcomes. CONCLUSIONS: SCC of the temporal bone is a highly
      malignant disease that is associated with high morbidity and mortality despite
      aggressive multimodal treatment. LEVEL OF EVIDENCE: 4.

PMID- 23553472
TI  - Pregnancy outcomes following gabapentin use: results of a prospective comparative
      cohort study.
AB  - OBJECTIVES: Our objectives were to 1) determine whether first-trimester use of
      gabapentin is associated with an increased risk for major malformations; 2)
      examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean
      birth weight and gestational age at delivery; and 3) examine rates of poor
      neonatal adaptation syndrome following late pregnancy exposure. METHODS: The
      study design was prospective. Women were included who initially contacted the
      services between 5 and 8 weeks with a comparison group of women exposed to
      nonteratogens, collected in a similar manner. RESULTS: We have data on 223
      pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies. The rates
      of major malformations were similar in both groups (p = 0.845). There was a
      higher rate of preterm births (p = 0.019) and low birth weight <2,500 g (p =
      0.033) in the gabapentin group. Among infants who were exposed to gabapentin up
      until delivery, 23 of 61 (38%) were admitted to either the neonatal intensive
      care unit or special care nursery for observation and/or treatment, vs 6 of 201
      (2.9%) live births in the comparison group (p < 0.001). There were 2 cases of
      possible poor neonatal adaptation syndrome in neonates exposed to gabapentin
      close to delivery, compared with none in the comparison group, although it must
      be noted that these infants were concomitantly exposed to other psychotropic
      drugs. Among the women who took gabapentin, the major indications were pain (n =
      90; 43%) and epilepsy (n = 71; 34%); the remainder were for other indications,
      mostly psychiatric. CONCLUSION: Our results suggest that although this sample
      size is not large enough to make any definitive conclusions, and there was no
      comparator group treated with other antiepileptic drugs, gabapentin use in
      pregnancy does not appear to increase the risk for major malformations. This
      finding and the increased risk for low birth weight and preterm birth require
      further investigation.

PMID- 23553473
TI  - Ultrasound as the first choice for peripheral nerve imaging?

PMID- 23553474
TI  - Detection of peripheral nerve pathology: comparison of ultrasound and MRI.
AB  - OBJECTIVE: To compare accuracy of ultrasound and MRI for detecting focal
      peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel
      syndromes. METHODS: We performed a retrospective review of patients referred for
      neuromuscular ultrasound to identify patients who had ultrasound and MRI of the
      same limb for suspected brachial plexopathy or mononeuropathies, excluding
      carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to
      diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic
      evaluation. RESULTS: We identified 53 patients who had both ultrasound and MRI of
      whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or
      clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed
      nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001).
      Nerve pathology was correctly excluded (true negative) with equal frequency by
      MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true
      positive or true negative) when MRI was not. These pathologies were typically
      (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view.
      MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients,
      often (5/7) because pathology was outside the MRI field of view. CONCLUSIONS:
      Imaging frequently detects peripheral nerve pathology and contributes to the
      differential diagnosis in patients with mononeuropathies and brachial
      plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent
      specificity (86%), and better identifies multifocal lesions than MRI. In
      sonographically accessible regions ultrasound is the preferred initial imaging
      modality for anatomic evaluation of suspected peripheral nervous system lesions.

PMID- 23553476
TI  - Outcomes for temporal lobe epilepsy operations may not be equal: a call for an
      RCT of ATL vs SAH.

PMID- 23553475
TI  - Systematic review and meta-analysis of standard vs selective temporal lobe
      epilepsy surgery.
AB  - OBJECTIVE: To compare standard anterior temporal lobectomy (ATL) with selective
      amygdalohippocampectomy (SAH) for postoperative seizure control in temporal lobe
      epilepsy (TLE). METHODS: We searched MEDLINE and Embase using Medical Subject
      Headings and keywords related to ATL and SAH. We included original research that
      directly compared seizure outcomes in patients undergoing SAH or ATL for TLE. A
      fixed-effect model was used to derive a pooled risk ratio (RR) for either an
      Engel Class I (free of disabling seizures) or a composite of an Engel Class I and
      II (rare disabling seizures) outcome. RESULTS: Of 4,675 abstracts initially
      identified by the search, 65 were reviewed as full text. Thirteen studies
      containing data from 8 countries (5 continents) met our inclusion criteria.
      Eleven studies comprising 1,203 patients demonstrated that participants were
      statistically more likely to achieve an Engel Class I outcome after ATL compared
      with SAH (risk ratio 1.32, 95% confidence interval [CI] 1.12-1.57; p < 0.01). The
      summary risk difference of 8% (95% CI 3%-14%) translates to a number needed to
      treat of 13 (95% CI 7-33) for 1 additional patient to achieve an Engel Class I
      outcome after ATL. The result remained significant when 2 studies that contained
      fewer than 15 participants in at least 1 arm were excluded and in analyses
      restricted to hippocampal sclerosis. CONCLUSIONS: Standard ATL confers an
      improved chance of achieving freedom from disabling seizures in patients with
      TLE. Improved seizure freedom must be balanced against the neuropsychological
      impact of each procedure. A randomized controlled trial is justified.

PMID- 23553477
TI  - NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern.
AB  - OBJECTIVE: To identify the mutated gene in a group of patients with an
      unclassified heritable white matter disorder sharing the same, distinct MRI
      pattern. METHODS: We used MRI pattern recognition analysis to select a group of
      patients with a similar, characteristic MRI pattern. We performed whole-exome
      sequencing to identify the mutated gene. We examined patients' fibroblasts for
      biochemical consequences of the mutant protein. RESULTS: We identified 6 patients
      from 5 unrelated families with a similar MRI pattern showing predominant
      abnormalities of the cerebellar cortex, deep cerebral white matter, and corpus
      callosum. The 4 tested patients had a respiratory chain complex I deficiency.
      Exome sequencing revealed mutations in NUBPL, encoding an iron-sulfur cluster
      assembly factor for complex I, in all patients. Upon identification of the
      mutated gene, we analyzed the MRI of a previously published case with NUBPL
      mutations and found exactly the same pattern. A strongly decreased amount of
      NUBPL protein and fully assembled complex I was found in patients' fibroblasts.
      Analysis of the effect of mutated NUBPL on the assembly of the peripheral arm of
      complex I indicated that NUBPL is involved in assembly of iron-sulfur clusters
      early in the complex I assembly pathway. CONCLUSION: Our data show that NUBPL
      mutations are associated with a unique, consistent, and recognizable MRI pattern,
      which facilitates fast diagnosis and obviates the need for other tests, including
      assessment of mitochondrial complex activities in muscle or fibroblasts.

PMID- 23553478
TI  - Hyperdopaminergic crises in familial dysautonomia: a randomized trial of
      carbidopa.
AB  - OBJECTIVE: The purpose of this study was to determine whether carbidopa
      (Lodosyn), an inhibitor of dopa-decarboxylase that blocks the synthesis of
      dopamine outside the brain, is an effective antiemetic in patients with familial
      dysautonomia (FD) and hyperdopaminergic nausea/retching/vomiting attacks.
      METHODS: We enrolled 12 patients with FD in an open-label titration and treatment
      study to assess the safety of carbidopa. We then conducted a randomized, double
      blind, placebo-controlled, crossover study to evaluate its antiemetic efficacy.
      RESULTS: Previous fundoplication surgery in each patient studied prevented
      vomiting, but all of the subjects experienced severe cyclical nausea and
      uncontrollable retching that was refractory to standard treatments. Carbidopa at
      an average daily dose of 480 mg (range 325-600 mg/day) was well tolerated. In the
      double-blind phase, patients experienced significantly less nausea and retching
      while on carbidopa than on placebo (p < 0.03 and p < 0.02, respectively). Twenty
      four-hour urinary dopamine excretion was significantly lower while on carbidopa
      (147 +/- 32 ug/gCr) than while on placebo (222 +/- 41ug/gCr, p < 0.05).
      CONCLUSIONS: Carbidopa is a safe and effective antiemetic in patients with FD,
      likely by reducing the formation of dopamine outside the brain. CLASSIFICATION OF
      EVIDENCE: This study provides Class II evidence that carbidopa is effective in
      reducing nausea/retching/vomiting in patients with FD.

PMID- 23553479
TI  - Rare cell capture technology for the diagnosis of leptomeningeal metastasis in
      solid tumors.
AB  - OBJECTIVE: To evaluate the utility of rare cell capture technology (RCCT) in the
      diagnosis of leptomeningeal metastasis (LM) from solid tumors through
      identification of circulating tumor cells (CTCs) in the CSF. METHODS: In this
      pilot study, CSF samples from 60 patients were analyzed. The main patient cohort
      consisted of 51 patients with solid tumors undergoing lumbar puncture for
      clinical suspicion of LM. Those patients underwent initial MRI evaluation and had
      CSF analyzed through conventional cytology and for the presence of CTCs using
      RCCT, based on immunomagnetic platform enrichment utilizing anti-epithelial cell
      adhesion molecule antibody-covered magnetic nanoparticles. An additional 9
      patients with CSF pleocytosis but without solid tumors were separately analyzed
      to ensure accurate differentiation between CTCs and leukocytes. RESULTS: Among
      the 51 patients with solid tumors, 15 patients fulfilled criteria for LM. CSF
      CTCs were found in 16 patients (median 20.7 CTCs/mL, range 0.13 to >150),
      achieving a sensitivity of 100% as compared with 66.7% for conventional cytology
      and 73.3% for MRI. One patient had a false-positive CSF CTC result (specificity =
      97.2%); however, that patient eventually met LM criteria 6 months after the tap.
      CSF CTCs were not found in any of the additional 9 patients with CSF pleocytosis.
      CONCLUSION: RCCT is an accurate, novel method for the detection of LM in solid
      tumors, potentially providing earlier diagnostic confirmation and sparing
      patients from repeat lumbar punctures.

PMID- 23553480
TI  - alpha-Synuclein in CSF of patients with severe traumatic brain injury.
AB  - OBJECTIVE: The study aims to examine alpha-synuclein in the CSF of patients with
      severe traumatic brain injury (TBI) and its relationship with clinical
      characteristics and long-term outcomes. METHODS: This prospective case-control
      study enrolled patients with severe TBI (Glasgow Coma Score <= 8) who underwent
      ventriculostomy. CSF samples were taken from each TBI patient at admission and
      daily for up to 8 days after injury and successively assessed by ELISA. Control
      CSF was collected for analysis from subjects receiving lumbar puncture for other
      medical reasons. We used trajectory analysis to identify distinct temporal
      profiles of CSF alpha-synuclein that were compared with clinical outcomes.
      RESULTS: CSF alpha-synuclein was elevated in TBI patients after injury as
      compared to controls (p = 0.0008). Overall, patients who died had higher
      concentrations (area under the curve) over 8 days of observation compared to
      those who survived at 6 months postinjury (p = 0.002). Two distinct temporal
      alpha-synuclein profiles were recognized over time. Subjects who died had
      consistently elevated alpha-synuclein levels compared to those who survived with
      alpha-synuclein levels near controls. High-risk trajectory was a strong and
      accurate predictor of death with 100% specificity and a very high sensitivity
      (83%). CONCLUSIONS: Taken together, these data support the hypothesis that in
      severe TBI patients, substantial increase of CSF alpha-synuclein may indicate
      widespread neurodegeneration and reflect secondary neuropathologic events
      occurring after injury. The determination of CSF alpha-synuclein may be a
      valuable prognostic marker, adding to the clinical assessment and creating
      opportunities for medical intervention.

PMID- 23553481
TI  - Cognitive changes predict functional decline in ALS: a population-based
      longitudinal study.
AB  - OBJECTIVE: To determine whether cognitive status in patients with amyotrophic
      lateral sclerosis (ALS) is a useful predictor of attrition and motor and
      cognitive decline. METHODS: Cognitive testing was undertaken in a large
      population-based cohort of incident ALS patients using a longitudinal, case
      control study design. Normative data for neuropsychological tests were generated
      using age-, sex-, and education-matched healthy controls who also underwent
      repeated assessments. Data were analyzed to generate models for
      progression/spread. RESULTS: One hundred eighty-six patients with ALS who had no
      evidence of C9orf72 hexanucleotide repeat expansion were enrolled. A second and
      third assessment were undertaken in 98 and 46 of the patients with ALS,
      respectively. Executive impairment at the initial visit was associated with
      significantly higher rates of attrition due to disability or death and faster
      rates of motor functional decline, particularly decline in bulbar function.
      Decline in cognitive function was faster in patients who were cognitively
      impaired at baseline. Normal cognition at baseline was associated with tendency
      to remain cognitively intact, and with slower motor and cognitive progression.
      CONCLUSIONS: Non-C9orf72-associated ALS is characterized by nonoverlapping
      cognitive subgroups with different disease trajectories. These findings have
      important implications for models of ALS pathogenesis, and for future clinical
      trial design.

PMID- 23553482
TI  - Topography of dilated perivascular spaces in subjects from a memory clinic
      cohort.
AB  - OBJECTIVE: To investigate whether the topography of dilated perivascular spaces
      (DPVS) corresponds with markers of particular small-vessel diseases such as
      cerebral amyloid angiopathy and hypertensive vasculopathy. METHODS: Patients were
      recruited from an ongoing single-center prospective longitudinal cohort study of
      patients evaluated in a memory clinic. All patients underwent structural, high
      resolution MRI, and had a clinical assessment performed within 1 year of scan.
      DPVS were rated in basal ganglia (BG-DPVS) and white matter (WM-DPVS) on T1
      sequences, using an established 4-point semiquantitative score. DPVS degree was
      classified as high (score > 2) or low (score <= 2). Independent risk factors for
      high degree of BG-DPVS and WM-DPVS were investigated. RESULTS: Eighty-nine
      patients were included (mean age 72.7 +/- 9.9 years, 57% female). High degree of
      WM-DPVS was more frequent than low degree in patients with presence of strictly
      lobar microbleeds (45.5% vs 28.4% of subjects). High BG-DPVS degree was
      associated with older age, hypertension, and higher white matter hyperintensity
      volumes. In multivariate analysis, increased lobar microbleed count was an
      independent predictor of high degree of WM-DPVS (odds ratio [OR] 1.53 [95%
      confidence interval (CI) 1.06-2.21], p = 0.02). By contrast, hypertension was an
      independent predictor of high degree of BG-DPVS (OR 9.4 [95% CI 1-85.2], p =
      0.04). CONCLUSIONS: The associations of WM-DPVS with lobar microbleeds and BG
      DPVS with hypertension raise the possibility that the distribution of DPVS may
      indicate the presence of underlying small-vessel diseases such as cerebral
      amyloid angiopathy and hypertensive vasculopathy in patients with cognitive
      impairment.

PMID- 23553484
TI  - Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and
      genetic spectrum.
AB  - OBJECTIVE: To report a series of 11 patients on the severe end of the spectrum of
      ryanodine receptor 1 (RYR1) gene-related myopathy, in order to expand the
      clinical, histologic, and genetic heterogeneity associated with this group of
      patients. METHODS: Eleven patients evaluated in the neonatal period with severe
      neonatal-onset RYR1-associated myopathy confirmed by genetic testing were
      ascertained. Clinical features, molecular testing results, muscle imaging, and
      muscle histology are reviewed. RESULTS: Clinical features associated with the
      severe neonatal presentation of RYR1-associated myopathy included decreased fetal
      movement, hypotonia, poor feeding, respiratory involvement, arthrogryposis, and
      ophthalmoplegia in 3 patients, and femur fractures or hip dislocation at birth.
      Four patients had dominant RYR1 mutations, and 7 had recessive RYR1 mutations.
      One patient had a cleft palate, and another a congenital rigid spine phenotype
      findings not previously described in the literature in patients with early-onset
      RYR1 mutations. Six patients who underwent muscle ultrasound showed relative
      sparing of the rectus femoris muscle. Histologically, all patients with dominant
      mutations had classic central cores on muscle biopsy. Patients with recessive
      mutations showed great histologic heterogeneity, including fibrosis, variation in
      fiber size, skewed fiber typing, very small fibers, and nuclear internalization
      with or without ill-defined cores. CONCLUSIONS: This series confirms and expands
      the clinical and histologic variability associated with severe congenital RYR1
      associated myopathy. Both dominant and recessive mutations of the RYR1 gene can
      result in a severe neonatal-onset phenotype, but more clinical and histologic
      heterogeneity has been seen in those with recessive RYR1 gene mutations. Central
      cores are not obligatory histologic features in recessive RYR1 mutations. Sparing
      of the rectus femoris muscle on imaging should prompt evaluation for RYR1
      associated myopathy in the appropriate clinical context.

PMID- 23553486
TI  - MicroRNA miR-24 promotes cell proliferation by targeting the CDKs inhibitors
      p27Kip1 and p16INK4a.
AB  - Cell cycle progression is controlled by numerous mechanisms ensuring correct cell
      division. The transition from one cell cycle phase to another occurs in an
      orderly fashion and is regulated by different cellular proteins. Therefore an
      alteration of the regulatory mechanisms of the cell cycle results in uncontrolled
      cell proliferation, which is a distinctive feature of human cancers. Recent
      evidences suggest that microRNAs (miRs) may also control the levels of multiple
      cell cycle regulators and therefore control cell proliferation. In fact miRs are
      a class of small non-coding RNAs, which modulate gene expression. They are
      involved in numerous physiological cellular processes and most importantly
      accumulating evidence indicates that many miRs are aberrantly expressed in human
      cancers. In this report we describe that miR-24 directly targets p27(Kip1) and
      p16(Ink4a) in primary keratinocyte and in different cancer derived cell lines
      promoting their proliferation, suggesting that miR-24 is involved in cyclin
      dependent kinase inhibitors post-transcriptional regulation and that upregulation
      of miR-24 may play a role in carcinogenesis.

PMID- 23553485
TI  - Brief report: citrullination within the atherosclerotic plaque: a potential
      target for the anti-citrullinated protein antibody response in rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate whether citrullinated proteins within the
      atherosclerotic plaque can be targeted by anti-citrullinated protein antibodies
      (ACPAs), forming stimulatory immune complexes that propagate the progression of
      atherosclerosis. METHODS: Protein lysates prepared from atherosclerotic segments
      of human aorta were assessed for the presence of citrulline-modified proteins,
      and specifically citrullinated fibrinogen (Cit-fibrinogen), by
      immunoprecipitation and/or immunoblotting followed by mass spectrometry.
      Immunohistochemical analysis of coronary artery plaque was performed to determine
      the presence of citrullinated proteins and peptidylarginine deiminase type 4 (PAD
      4). Serum levels of anti-cyclic citrullinated peptide (anti-CCP), anti
      citrullinated vimentin (anti-Cit-vimentin), and anti-Cit-fibrinogen antibodies
      were measured in 134 women with seropositive rheumatoid arthritis; these subjects
      had previously been characterized for the presence of subclinical
      atherosclerosis, by electron beam computed tomography scanning. RESULTS: Western
      blot analysis of atherosclerotic plaque lysates demonstrated several
      citrullinated proteins, and the presence of Cit-fibrinogen was confirmed by
      immunoprecipitation and mass spectrometry. Immunohistochemical analysis showed
      colocalization of citrullinated proteins and PAD-4 within the coronary artery
      plaque. In age-adjusted regression models, antibodies targeting Cit-fibrinogen
      and Cit-vimentin, but not CCP-2, were associated with an increased aortic plaque
      burden. CONCLUSION: Citrullinated proteins are prevalent within atherosclerotic
      plaques, and certain ACPAs are associated with the atherosclerotic burden. These
      observations suggest that targeting of citrullinated epitopes, specifically Cit
      fibrinogen, within atherosclerotic plaques could provide a mechanism for the
      accelerated atherosclerosis observed in patients with RA.

PMID- 23553487
TI  - Photophysics of novel coumarin-labeled depsipeptides in solution: sensing
      interactions with SDS micelle via TICT model.
AB  - N-Acylbenzotriazoles enable the synthesis (69-92% yield) of blue to green
      fluorescent coumarin-labeled depsidipeptides 8a-f (quantum yields 0.004-0.97) and
      depsitripeptides 12a-d (quantum yields 0.02-0.96). Detailed photophysical studies
      of fluorescent coumarin-labeled depsipeptides 8a-f and 12a-d are reported for
      both polar protic and polar aprotic solvents. 7-Methoxy and 7
      diethylaminocoumarin-3-ylcarbonyl depsipeptides 8c,f and 12d are highly solvent
      sensitive. These highly fluorescent compounds could be useful for peptide assays.
      Further photophysical studies of 7-diethylaminocoumarin-labeled depsipeptides
      8c,12d within the micellar microenvironment of SDS reflect their ability to bind
      with the biological membrane, suggesting potential applications in the fields of
      bio- and medicinal chemistry.

PMID- 23553488
TI  - Identification of differentially expressed genes involved in laccase production
      in tropical white-rot fungus Polyporus sp. PG15.
AB  - Carbon sources and copper ion are the main influencing factors on the production
      of fungal laccase. To investigate the regulation of carbon source and copper ion
      in laccase production on the molecular level in tropical white-rot fungus PG15, a
      comparative analysis of gene expression patterns was performed by cDNA-amplified
      fragment length polymorphism (AFLP) technique. Selective amplifications with 120
      primer combinations allowed the identification of 92 differentially expressed
      transcript-derived fragments (TDFs), ranging from 200 to 750 bp in size. The TDFs
      were from PG15 supplemented with different carbon sources and copper ion
      concentrations, majority of which downregulated laccase production. Twenty-one
      fragments that matched the database were functionally annotated and analyzed
      according to the up- and downregulation patterns identified by cDNA-AFLP. These
      fragments were probably involved in laccase production at the metabolism, signal
      transduction, transcription, or post-translation levels. This study provides the
      first catalog of genes involved in laccase production, together with their
      putatively functional annotations. These data provide potential candidates for
      improving laccase production in fungi by marker-assisted selection or genetic
      engineering. 

PMID- 23553489
TI  - Accurate screened exchange band structures for the transition metal monoxides
      MnO, FeO, CoO and NiO.
AB  - We report calculations of the band structures and density of states of the four
      transition metal monoxides MnO, FeO, CoO and NiO using the hybrid density
      functional sX-LDA ('screened exchange local density approximation'). Late
      transition metal oxides are prototypical examples of strongly correlated
      materials, which pose challenges for electronic structure methods. We compare our
      results with available experimental data and show that our calculations generally
      yield accurate predictions for the fundamental band gaps and valence bands, in
      favourable agreement with previously reported theoretical studies. For MnO, the
      band gaps are still underestimated, suggesting additional many-body effects that
      are not captured by our screened hybrid functional approach.

PMID- 23553490
TI  - Bone morphogenetic protein-2-impregnated biomimetic scaffolds successfully induce
      bone healing in a marginal mandibular defect.
AB  - OBJECTIVES/HYPOTHESIS: To test the osteoregenerative potential and dosing of bone
      morphogenetic protein-2 (BMP-2)-impregnated biomimetic scaffolds in a rat model
      of a mandibular defect. STUDY DESIGN: Prospective study using an animal model.
      METHODS: Varied doses of BMP-2 (0.5, 1, 0.5, 0.5 in microspheres, 5, and 15 MUg)
      were absorbed onto a biomimetic scaffold. Scaffolds were then implanted into
      marginal mandibular defects in rats. Blank scaffolds and unfilled defects were
      used as negative controls. Two months postoperatively, bone healing was analyzed
      with microcomputerized tomography (microCT). RESULTS: MicroCT analysis
      demonstrated that all doses of BMP-2 induced successful healing of marginal
      mandibular defects in a rat mandible. Increasing doses of BMP-2 on the scaffolds
      produced increased tissue healing, with 15 MUg demonstrating significantly more
      healing than all other dosing (P < .01). CONCLUSIONS: BMP-2-impregnated
      biomimetic scaffolds successfully induce bone healing in a marginal mandibular
      defect in the rat. Percentage healing of defect, percentage of bone within healed
      tissue, and total bone volume are all a function of BMP-2 dosing. There appears
      to be an optimal dose of 5 MUg beyond which there is no increase in bone volume.
      LEVEL OF EVIDENCE: NA.

PMID- 23553491
TI  - Analysis of age-related global DNA methylation in chicken.
AB  - DNA methylation is an epigenetic modification that plays an important role in the
      normal development and function of organisms. The level of DNA methylation is
      species-, tissue-, and organelle-specific, and the methylation pattern is
      determined during embryogenesis. DNA methylation has also been correlated with
      age. The aim of this study was to determine the global DNA methylation levels and
      their correlation with age in the chicken, using a Polish autosexing chicken
      breed, Polbar. A quantitative technique based on an immunoenzymatic assay was
      used for global DNA methylation analysis. The results show increased global DNA
      methylation levels with older Polbar embryos. Global DNA methylation levels
      decrease with the age of hens in the postembryonic stage. This study expands the
      current knowledge of the Polbar epigenome and the general knowledge of the
      function of epigenetic mechanisms in birds. 

PMID- 23553492
TI  - RANKL is downregulated in bone cells by physical activity (treadmill and
      vibration stimulation training) in rat with glucocorticoid-induced osteoporosis.
AB  - The aim of this study was to investigate bone tissue and plasma levels of RANKL
      and OPG in rats with prednisolone-induced osteoporosis and to evaluate the
      outcomes of physical activity on the skeletal system by treadmill and vibration
      platform training. Osteoporosis is a disease characterised by low bone mass and
      structural deterioration of bone tissue leading to bone fragility. Vibration
      exercise is a new and effective measure to prevent muscular atrophy and
      osteoporosis. The animals were divided into 5 groups. 1: control rats; 2: rats
      with osteoporosis receiving prednisolone; 3: rats receiving prednisolone and
      treadmill training; 4: rats receiving prednisolone and vibration stimulation
      training; 5: rats receiving prednisolone, treadmill and vibration stimulation
      training. For bone evaluations we used whole-body scans, histology and
      histomorphometric analysis. RANKL and OPG expression was evaluated by
      immunohistochemistry and biochemical analysis. After treatment, our data
      demonstrated that RANKL expression was significantly increased in groups 2 and 3
      and decreased in groups 4 and 5. Conversely, OPG expression was significantly
      decreased in groups 2 and 3 and increased in groups 4 and 5. In conclusion, our
      findings suggest that mechanical stimulation inhibits the activity of RANKL. This
      finding provides new insights into the occurrence and progression of
      osteoporosis.

PMID- 23553493
TI  - Odour-active compounds in guava (Psidium guajava L. cv. Red Suprema).
AB  - BACKGROUND: Solid phase microextraction and simultaneous distillation-extraction
      combined with GC-FID, GC/MS, aroma extract dilution analysis and odour activity
      values were used to analyse volatile compounds from guava (Psidium guajava L. cv.
      Red Suprema) and to estimate the most odour-active compounds. RESULTS: The
      analysis led to the detection of 141 compounds, 121 of which were positively
      identified. The composition of guava fruit volatiles included 43 esters, 37
      terpenes, 18 aldehydes, 16 alcohols, ten acids, six ketones, four furans and
      seven miscellaneous compounds. CONCLUSION: Seventeen odorants were considered as
      odour-active compounds, with (E)-beta-ionone, ethyl hexanoate, ethyl butanoate,
      hexanal, (Z)-3-hexenal, hexyl acetate, (E)-2-hexenal and limonene contributing
      most to the typical guava aroma of this cultivar.

PMID- 23553494
TI  - Catholic identity and charity care in the era of health reform.
AB  - Catholic healthcare institutions live amidst tension between three intersecting
      primary values, namely, a commitment of service to the poor and vulnerable,
      promoting the common good for all, and financially sustainability. Within this
      tension, the question sometimes arises as to whether it is ever justifiable,
      i.e., consistent with Catholic identity, to place limits on charity care. In this
      article we will argue that the health reform measures of the Affordable Care Act
      do not eliminate this tension but actually increase the urgency of addressing it.
      Moreover, we will conclude that the question of limiting charity care in a manner
      that is consistent with the obligations of Catholic identity around serving the
      poor and vulnerable, promoting the common good, and remaining financially
      sustainable is not a question of if, but of how such limits are established. Such
      limits, however, cannot be established in light of one overriding moral
      consideration or principle, but must be established in light of a multitude of
      principles guiding us to a holistic understanding of the interrelatedness of the
      moral dimensions of Catholic identity.

PMID- 23553495
TI  - Endoplasmic reticulum resident heat shock protein-gp96 as morphogenetic and
      immunoregulatory factor in syngeneic pregnancy.
AB  - The severe remodeling of endometrial stroma during blastocyst adhesion and
      trophoblast invasion initiates at maternal-fetal interface the reaction of
      evolutionary old heat shock response, in which heat shock proteins, as molecular
      chaperons, monitor the configurations of newly synthesized proteins and prevent
      the formation of functionless aggregates of misfolded proteins, targeting them to
      degradation by a the ubiquitin-proteasome system. In addition, the endoplasmic
      reticulum (ER)-resident HSPs, such as gp96/GRP94 may, after binding to CD91 and
      TLRs, elicit antigen-specific and antigen-unspecific immune responses, owing to
      its peptide-chaperoning capacity and ability to activate APCs. Considering these
      properties, we examined tissue expression of gp96 at the maternal-fetal interface
      and in the maternal liver and spleen on the 16th day of undisturbed syngeneic
      pregnancy and after the treatment with peptidoglycan monomer linked with zinc
      (PGM-Zn). The data showed that in undisturbed pregnancy the gp96, CD91 and TLR2
      were markedly expressed on extravillous and villous trophoblast. PGM-Zn enhanced
      these findings, as well as the number of uterine natural killer cells and local
      NFkappaB immunoreactivity. Gp96 expression arose also in the maternal spleen and
      liver, where an accumulation of NKT cells or gammadeltaT lymphocytes was seen.
      The data point to roles of gp96 in maintenance of proteostasis and local and
      systemic immune balance in pregnancy complicated by infection.

PMID- 23553496
TI  - Rumination and impaired cortisol recovery following a social stressor in
      adolescent depression.
AB  - Response styles theory promotes rumination as a central cognitive construct
      driving negative mood and depression, and past research suggests that at least
      part of the mechanism driving rumination's depressogenic effect is through
      inhibiting the individual's ability to shift attentional focus away from negative
      environmental stimuli. In the current study, we hypothesized that high trait
      rumination would be associated with impaired recovery of the body's biological
      response to psychological stress. In a community sample of depressed (n = 31) and
      non-depressed (n = 33) adolescents we assessed rumination and the more adaptive
      trait of distraction and problem-solving with the Children's Response Styles
      Questionnaire (CRSQ; Abela 2000), and diagnostic status was confirmed using the
      Child and Adolescent Schedule of Affective Disorders and Schizophrenia (K-SADS;
      Kaufman et al. Journal of the American Academy of Child and Adolescent Psychiatry
      36:980-988, 1997). Participants completed the Trier Social Stress Test (TSST;
      Kirschbaum et al. Neuropsychobiology 28:76-81, 1993), and the focus of our
      analyses was the change in salivary cortisol concentration between peak cortisol
      output (25 min post-stressor) and a sample taken during the "Recovery" period 65
      minutes post-stressor. Consistent with the predictions of response style theory,
      among the depressed adolescents only, high trait rumination was associated with
      delayed post-stressor cortisol recovery, whereas high trait distraction and
      problem-solving was associated with more rapid recovery. In contrast, response
      styles were not associated with cortisol recovery in the non-depressed group.
      These findings implicate impaired post-stress cortisol recovery as a potential
      mechanism underlying the pathological effect of rumination on the development and
      maintenance of Major Depressive Disorder (MDD).

PMID- 23553497
TI  - Bone health and human immunodeficiency virus infection.
AB  - Low bone mineral density is common among persons with human immunodeficiency
      virus (HIV) infection, and studies reporting increased fracture rates in this
      patient population are emerging. The causes of low bone mineral density,
      osteoporosis, and fractures in persons with HIV are likely multifactorial,
      involving traditional risk factors, HIV infection, and exposure to antiretroviral
      treatment. Specific antiretrovirals such as tenofovir may cause a greater loss of
      bone mineral density compared with other agents and have recently been linked to
      an increased risk for fracture. As a result, recent treatment guidelines suggest
      that clinicians consider avoiding tenofovir as initial therapy in postmenopausal
      women. Evaluating bone mineral density and vitamin D status in persons with HIV
      may be important steps in identifying those requiring pharmacotherapy; however,
      the appropriate timing for bone mineral density and vitamin D screening is
      uncertain, as is the appropriate method of replacing vitamin D in HIV-positive
      patients who are deficient. Further study is necessary to definitively determine
      the approach to evaluating bone health and managing low bone mineral density and
      vitamin D deficiency in patients with HIV infection.

PMID- 23553499
TI  - Smooth ROC curves and surfaces for markers subject to a limit of detection using
      monotone natural cubic splines.
AB  - The use of ROC curves in evaluating a continuous or ordinal biomarker for the
      discrimination of two populations is commonplace. However, in many settings,
      marker measurements above or below a certain value cannot be obtained. In this
      paper, we study the construction of a smooth ROC curve (or surface in the case of
      three populations) when there is a lower or upper limit of detection. We propose
      the use of spline models that incorporate monotonicity constraints for the
      cumulative hazard function of the marker distribution. The proposed technique is
      computationally stable and simulation results showed a satisfactory performance.
      Other observed covariates can be also accommodated by this spline-based approach.

PMID- 23553500
TI  - Diagnostic criteria for primary osteoporosis: year 2012 revision.
AB  - In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese
      Society for Bone and Mineral Research) established the Osteoporosis Diagnostic
      Criteria Review Committee. Following discussion held at the 13th scientific
      meeting of the Society in 1996, the Committee, with the consensus of its members,
      proposed diagnostic criteria for primary osteoporosis. The Committee revised
      those criteria in 1998 and again in 2000. The Japanese Society for Bone and
      Mineral Research and Japan Osteoporosis Society Joint Review Committee for the
      Revision of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining
      international consistency and made a revised edition based on the new findings in
      2012.

PMID- 23553501
TI  - Incidence and bone biopsy findings of atypical femoral fractures.
AB  - Bisphosphonates are widely used in the treatment of osteoporosis. It has been
      suggested that bisphosphonate treatment may be associated with atypical femoral
      fractures (AFFs), severely suppressed bone turnover rate, and decreased
      mineralization. We studied bone properties using bone quantitative
      histomorphometry and Fourier transform infrared spectroscopic imaging (FTIRI) on
      patients with AFFs. Further, the incidence of AFFs was estimated. Patient records
      of Kuopio University Hospital, Finland from January 2007 to June 2009 were
      reviewed to identify all patients who had sustained and had been operated for AFF
      (n = 8). The incidence of AFFs among patients on bisphosphonates was 0.61
      fractures/1,000 patients per year, compared to 0.0067/1,000 per year among
      untreated patients. The patients that underwent bone biopsy (n = 4) were
      postmenopausal women (aged 55.5-81.1 years) who had been treated with
      bisphosphonates for over 4 years. Histomorphometry revealed low trabecular bone
      volume. Bone formation and resorption parameters tended to be low. Trabecular
      bone single labels were detected in one patient in the region of interest. In the
      extended label search, trabecular bone double labels were found in two patients.
      Based on FTIRI results, higher phosphate-to-amide I ratio and collagen maturity
      were found compared to normal samples. The heterogeneity of phosphate-to-amide I
      ratio was low. Overall incidence of atypical femoral fractures is low. The poor
      fracture resistance in some patients on long-term bisphosphonate-therapy could be
      explained by low bone formation, and changes in bone composition, i.e., higher
      degree of mineralization, increased collagen maturity, and decreased
      heterogeneity of the degree of mineralization. 

PMID- 23553502
TI  - Assessment of metals pollution on agricultural soil surrounding a lead-zinc
      mining area in the Karst region of Guangxi, China.
AB  - Soil samples were collected on farmland in a lead-zinc mining area in the Karst
      region of Guangxi, China. The contamination of the soil by eight metals (Cd, Hg,
      As, Cu, Pb, Cr, Zn, Ni) was determined. Among all these metals, Cd is the most
      serious pollutant in this area. Zn, Hg as well asPb can also be measured at high
      levels, which may affect the crop production. All other metals contributed
      marginally to the overall soil contamination. Besides the evaluation of single
      metals, the Nemerow synthetic index indicated that the soil is not suitable for
      agricultural use.

PMID- 23553503
TI  - Heavy metal tolerance in metal hyperaccumulator plant, Salvinia natans.
AB  - Metal tolerance capacity of Salvinia natans, a metal hyperaccumulator, was
      evaluated. Plants were exposed to 10, 30 and 50 mg L-1 of Zn, Cd, Co, Cr, Fe, Cu,
      Pb, and Ni. Plant biomass, photosynthetic efficiency, quantum yield,
      photochemical quenching, electron transport rate and elemental (%C, H and N)
      constitution remained unaffected in Salvinia exposed to 30 mg L-1 of heavy
      metals, except for Cu and Zn exposed plants, where significant reductions were
      noted in some of the measured parameters. However, a significant decline was
      noted in most of the measured parameters in plants exposed to 50 mg L-1 of metal
      concentration. Results suggest that Salvinia has fairly high levels of tolerance
      to all the metals tested, but the level of tolerance varied from metal to metal.

PMID- 23553504
TI  - Mercury concentrations in South Atlantic swordfish, Xiphias gladius, caught off
      the coast of Brazil.
AB  - This study evaluated the concentrations of mercury in fillets (anterior, middle,
      and end regions) from the swordfish, Xiphias gladius, and the relationships
      between mercury concentration and fish weight, as well as the region of
      collection. Of a total of 697 swordfish analyzed, 11 had mercury concentrations
      above 1 mg/kg, 421 were between 0.5 and 1.0 mg/kg, and 265 were below 0.5 mg/kg.
      The anterior and posterior regions had greater concentrations of mercury than the
      middle region, and fish caught off the northern coast of Brazil had a higher
      concentration than those caught off the southern coast.

PMID- 23553505
TI  - Date fruit: chemical composition, nutritional and medicinal values, products.
AB  - Date fruit has served as a staple food in the Arab world for centuries. Worldwide
      production of date fruit has increased almost threefold over the last 40 years,
      reaching 7.68 million tons in 2010. Date fruit can provide many essential
      nutrients and potential health benefits to the consumer. Date fruit goes through
      four ripening stages named kimri, khalal, rutab and tamer. The main chemical
      components of date fruit include carbohydrates, dietary fibre, enzymes, protein,
      fat, minerals, vitamins, phenolic acids and carotenoids. The chemical composition
      of date fruit varies according to ripening stage, cultivar, growing environment,
      postharvest conditions, etc. The nutritional and medicinal activities of date
      fruit are related to its chemical composition. Many studies have shown that date
      fruit has antioxidant, antimutagenic, anti-inflammatory, gastroprotective,
      hepatoprotective, nephroprotective, anticancer and immunostimulant activities.
      Various date fruit-based products such as date syrup, date paste, date juice and
      their derived products are available. Date by-products can be used as raw
      materials for the production of value-added products such as organic acids,
      exopolysaccharides, antibiotics, date-flavoured probiotic-fermented dairy
      produce, bakery yeasts, etc. In this paper the chemical composition and
      nutritional and medicinal values of date fruit as well as date fruit-based
      products are reviewed.

PMID- 23553507
TI  - Individual and national level associations between economic deprivation and
      partner violence among college students in 31 national settings.
AB  - This study expands previous work by examining individual and national level
      effects of economic deprivation on partner violence among college students. Three
      main hypotheses were tested: (1) individual level economic deprivation (i.e.,
      ability to meet daily needs and family income) is associated with partner
      violence, (2) gross national income is associated with the mean rates of partner
      violence across nations, and (3) the association between individual level
      economic deprivation and partner violence varies according to the economic
      national context as measured by gross national income. Data for 14,090
      participants from 31 nations came from the International Dating Violence Study
      that queried university students about violence in their relationships and
      relevant risk factors. A series of overdispersed Poisson hierarchical linear
      regression models were specified to test the hypotheses. Ability to meet daily
      needs, but not family income, was associated with rates of partner violence.
      Gross national income was also associated with mean rates of partner violence
      across nations as well as the relationships between ability to meet daily and
      partner violence and between family income and partner violence. The findings
      show the importance of context, as indicated by national economic standing, on
      rates of partner violence. Not only do economically deprived individuals
      experience more partner violence, but those living in poorer nations experience
      more partner violence, regardless of individual economic deprivation. Limitations
      of the study include a non-random sample and substantial variation in the study
      sites beyond economic standing. Nonetheless, findings indicate efforts to
      confront partner violence must also call for cross-national economic development.

PMID- 23553506
TI  - Comparative review of the safety and efficacy of ferric carboxymaltose versus
      standard medical care for the treatment of iron deficiency anemia in bariatric
      and gastric surgery patients.
AB  - BACKGROUND: Iron deficiency anemia (IDA) is a common finding in patients after
      bariatric surgery. The cause is multifactorial including reduced oral iron intake
      and malabsorption. While many patients can be managed with oral supplements,
      parenteral iron may be needed to restore and maintain iron stores. METHODS:
      Subjects who had previous bariatric surgery and had participated in phase 3
      industry-sponsored clinical trials designed to assess the safety and/or efficacy
      of intravenous (IV) ferric carboxymaltose (FCM) were retrospectively selected
      from the databases of each of these studies. Demographic data, efficacy measures
      [hemoglobin, ferritin, and transferrin saturation (TSAT)], and adverse events
      were compared between FCM and other agents utilized as comparators in the trials.
      RESULTS: Two hundred eighty-one subjects from the intention to treat (ITT)
      population were included (mean age 49 years, BMI 33 kg/m(2), including 253
      females). FCM had similar or improved efficacy (p < 0.05) in terms of increasing
      hemoglobin, ferritin, and TSAT values when compared to other iron products used
      as standard of care for IDA. The incidence of adverse events in the FCM patients
      (n = 123) versus patients receiving any IV iron (n = 126) was 61 and 56.3 %,
      respectively. The adverse events were similar in both groups with the exception
      of a transient decrease in serum phosphate which was observed more frequently in
      the FCM group. CONCLUSIONS: These data in post-bariatric surgery IDA patients
      suggest that FCM is a safe and effective alternative to existing iron products
      permitting higher and thus less frequent individual doses.

PMID- 23553508
TI  - Neuropathic features of joint pain: a community-based study.
AB  - OBJECTIVE: Quantitative sensory testing (QST) and questionnaire-based assessments
      have been used to demonstrate features of neuropathic pain in subjects with
      musculoskeletal pain. However, their direct relationship has not been
      investigated in the community. The purpose of this study was to conduct an
      observational study to describe the characteristics of joint pain and to examine
      the relationship between QST measures and the PainDETECT Questionnaire (PD-Q).
      METHODS: Warm detection, heat pain, and mechanical pain thresholds as well as
      mechanical pain sensitivity over the sternum were determined and the PD-Q scores
      were calculated in a cross-sectional study of 462 participants in the Chingford
      Study. Comparisons were made between subjects with and those without joint pain.
      Logistic regression modeling was used to describe the association between
      neuropathic pain features, as determined by the PD-Q score, and each of the QST
      measures individually, adjusting for age, body mass index, and use of pain
      modifying medications. RESULTS: A total of 66.2% of the subjects reported recent
      joint pain, with a median average pain severity of 5 of 10. There was increased
      sensitivity to painful stimuli in the group with pain as compared to the pain
      free group, and this persisted after stratification by pain-modifying medication
      use. While only 6.7% of subjects had possible neuropathic pain features and 1.9%
      likely neuropathic pain features according to the standard PD-Q thresholds,
      features of neuropathic pain were common and were present in >50% of those
      reporting pain of at least moderate severity. Heat pain thresholds and mechanical
      pain sensitivity were significantly associated with features of neuropathic pain
      identified using the PD-Q, with an odds ratio (OR) of 0.88 (95% confidence
      interval [95% CI] 0.79-0.97; P = 0.011) and an OR of 1.24 (95% CI 1.04-1.48; P =
      0.018), respectively. CONCLUSION: QST measures and the PD-Q identified features
      of neuropathic pain in subjects in this community-based study, with significant
      overlap between the findings of the two techniques.

PMID- 23553509
TI  - Aclidinium bromide twice daily for the treatment of chronic obstructive pulmonary
      disease: a review.
AB  - The inhaled, long-acting muscarinic antagonist, aclidinium bromide, was indicated
      in July 2012 in Europe and the USA for the maintenance of bronchodilator
      treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in
      adults. Although initially investigated as a once-daily agent, a lower than
      expected improvement in trough forced expiratory volume over 1 s prompted re
      evaluation as a twice-daily (b.i.d.) regimen. The dose approved for use in
      Europe, 400 MUg b.i.d., achieved statistically significant improvements in lung
      function, reductions in breathlessness, and improved health-related quality of
      life (HRQoL) for up to 24 weeks of treatment in the pivotal phase 3 trials
      (AClidinium in Chronic Obstructive Respiratory Disease I [ACCORD COPD I] [12
      weeks] and Aclidinium To Treat Airway obstruction In COPD patieNts [ATTAIN] [24
      weeks]). These improvements were sustained during maintenance therapy of up to 52
      weeks. Pooled data from the ATTAIN and ACCORD studies (both included a placebo
      arm) showed that exacerbation frequency was significantly reduced, although
      neither study was prospectively designed to evaluate this endpoint.
      Pharmacological and preclinical studies demonstrated the low systemic
      bioavailability of aclidinium and the low propensity to induce cardiac
      arrhythmias. The good tolerability of aclidinium was confirmed in the phase 3
      program up to 52 weeks of treatment. The adverse event (AE) profile of the
      approved dose, 400 MUg b.i.d., was similar to that of placebo, with a low
      incidence of anticholinergic and cardiac AEs. Aclidinium is delivered via the
      Genuair((r)) multidose dry powder inhaler (Almirall Sofotec GmBH, Bad Homburg,
      Germany). The device is simple to use with multiple feedback mechanisms ensuring
      consistent dose delivery. In summary, aclidinium 400 MUg b.i.d. is effective for
      the treatment of patients with COPD, offering improvements in lung function,
      breathlessness, and HRQoL, with a good safety profile and a low incidence of
      anticholinergic and cardiac AEs.

PMID- 23553510
TI  - Combination therapy in hypertension.
AB  - Hypertension is recognized as a major risk factor for cardiovascular and renal
      diseases and represents the leading cause of mortality worldwide. In spite of
      proven benefits of hypertension treatment, blood pressure control rates are poor,
      even in high-income countries with virtually full-access to therapies. Nearly 75%
      of hypertensive patients do not achieve adequate control with monotherapy, thus
      needing combination treatment. Strategies to improve blood pressure control
      include the prompt shift from monotherapy to combination therapy, the initial
      treatment with a two-drug combination, and the use of fixed-dose combinations in
      a single pill. Currently, preferred combinations include a renin-angiotensin
      blocker, either an angiotensin-converting enzyme inhibitor or an angiotensin
      receptor blocker plus a calcium channel blocker or a diuretic. Some patients will
      also require a triple combination to achieve blood pressure control.

PMID- 23553511
TI  - Polypharmacy and potentially inappropriate medication in the adult, community
      dwelling population in Switzerland.
AB  - BACKGROUND: Polypharmacy and potentially inappropriate medication (PIM) are
      associated with adverse outcomes such as hospitalization, loss of productivity,
      and death. OBJECTIVE: This study evaluates the prevalence of polypharmacy and PIM
      in the adult community-dwelling population in Switzerland. METHODS: The analysis
      is done based on claims data from the largest health insurance in Switzerland. We
      calculated the number of medications submitted for reimbursement, the proportion
      of persons with polypharmacy, and the proportion of persons receiving PIM
      according to the 2003 Beers criteria and the PRISCUS list. Additionally, we
      estimated cost for medications and PIM, and identified the most prevalent groups
      of PIM according to the Anatomical Therapeutic Chemical Classification System
      (ATC). RESULTS: 17 % of the adult community-dwelling population in Switzerland
      received 5 or more medications which is one of the common definitions of
      polypharmacy, and over 21 % of adults aged more than 65 years had a PIM according
      to 2003 Beers criteria or the PRISCUS list. The most prevalent classes of PIM
      were psycholeptics, sex hormones, psychoanaleptics, and antiinflammatory drugs.
      CONCLUSION: Although the present study has a number of limitations, we conclude
      that the prevalence of polypharmacy and PIM in Switzerland is high. A broad
      spectrum of interventions on the individual level as well as on the population
      level is urgently needed.

PMID- 23553512
TI  - Medication (re)fill adherence measures derived from pharmacy claims data in older
      Americans: a review of the literature.
AB  - Medication nonadherence is a significant public health problem that affects the
      health and well-being of older Americans while burdening the US healthcare
      system. Pharmacy claims data have gained importance in deriving objective
      medication (re)fill adherence measures; however, little is known about
      application of such measures in older Americans. The objective of this study was
      to assess the types and characteristics of pharmacy claims-derived medication
      (re)fill adherence measures used in older Americans. A comprehensive literature
      search strategy was employed to identify all articles using pharmacy claims data
      to measure (re)fill adherence to prescription medications in older Americans aged
      65+ years. Included were articles reporting original research studies conducted
      and published in the USA in English between 1 January 2000 and 1 November 2012.
      The basic search used multiple key terms indicating adherence, combined with the
      term "medication" and the term "pharmacy claims or administrative claims." Due to
      the variety of measure names used in the literature, a more specific search was
      added to repeat the basic search for 29 previously used medication (re)fill
      adherence measure names. Articles identified through the database search were
      manually reviewed to select only articles meeting the inclusion criteria. The
      search resulted in a total of 36 articles. Information on medication (re)fill
      measurements were extracted and summarized. The 36 articles used 20 differently
      named measures under the three main concepts: medication adherence, persistence,
      and discontinuation. Measures of medication adherence cumulatively assessed the
      proportion of time at which medications were (not) filled over a predefined
      observation period (e.g., medication possession ratio). Measures of medication
      persistence assessed the continuity of medication filling over a specified time
      period, while medication discontinuation measures focused on termination of
      medication (re)fills. Overall, almost two thirds of all identified articles used
      a single medication (re)fill adherence measure. Among them, 77 % used a
      medication possession measure. The term "medication possession ratio" (MPR) was
      used most frequently (65 %), followed by the "proportion of days covered" (PDC;
      30 %). No single measure can be generally recommended for the use in older
      Americans. The challenges in using pharmacy claims-based medication (re)fill
      adherence measures in older Americans include a lack of consensus terminology and
      algorithms among measures of the same concepts, insufficient transparency of
      individual measure operationalization, and inadequate consideration of unique
      characteristics of the older population, such as temporary nursing home care.
      Although medication (re)fill adherence measures may be well suited for measuring
      medication adherence in older Americans, little guidance is available on how to
      use them in this population. Further efforts need to be given to the development
      and standardization of pharmacy claims-based medication (re)fill measures that
      are specifically tailored toward use in older Americans.

PMID- 23553513
TI  - Advances in conditioning regimens for older adults undergoing allogeneic stem
      cell transplantation to treat hematologic malignancies.
AB  - Allogeneic stem cell transplantation (SCT) is a potentially curative treatment
      for patients with hematological malignancies. These diseases, however, have their
      peak incidence in the sixth to eighth decades of life. Historically, elderly
      patients have been considered unsuitable candidates for SCT because of high
      treatment-related mortality (TRM). Over the past 15 years, the use of reduced
      intensity conditioning (RIC) regimens before SCT has allowed patients in the
      sixth and seventh decades of life to be routinely transplanted. Despite major
      differences among transplant centers in the intensity and composition of the
      conditioning regimen and immunosuppression, choice of graft source, postgraft
      immunomodulation, and supportive care, there has been a dramatic decrease in TRM,
      allowing safer delivery of SCT. Major obstacles to SCT in elderly patients
      include donor availability, graft-versus-host disease, delayed immune recovery,
      multiple comorbidities, and chemo refractoriness. Here we review the current
      results of SCT in elderly patients, focusing on the role of RIC, and using
      myeloid diseases as the model for discussion.

PMID- 23553514
TI  - Treatment of bleeding upper aerodigestive tract tumor-a novel approach with
      antifibrinolytic agent: case series and literature review.
AB  - OBJECTIVES/HYPOTHESIS: Symptomatic bleeding among patients with advanced upper
      aerodigestive tract tumor is a challenging problem. Given the limited options for
      topical treatment, embolization is often required to control the hemorrhage.
      There are recent reported cases of novel and successful treatment of patients
      with recalcitrant tracheo-bronchial bleed with tranexamic acid. We therefore
      described our initial experience of four consecutive cases of patients with
      bleeding from advanced aerodigestive tract tumor, successfully treated with oral
      tranexamic acid. STUDY DESIGN: Case series. METHODS: Case series of four
      consecutive patients with acute bleed from upper aerodigestive tract tumors,
      treated with oral tranexamic acid. Tranexamic acid was administered topically and
      systemically (1gm PO QID) for the orophayngeal and supraglottic tumor cases,
      where as systemic-only therapy were administered to the patients with nasal and
      nasopharyngeal tumors. RESULTS: None of the patients experienced further bleeding
      following the commencement of tranexamic acid treatment, and no adverse effect
      was noted. These are the first reported cases of symptomatic upper aerodigestive
      hemorrhage being controlled with tranexamic acid. It is increasingly being used
      in patients with life-threatening bleeding following trauma and major surgery.
      The optimum dose of tranexamic acid is undetermined. In vivo studies suggested
      concentrations of 10 MUg/mL to 16 MUg/mL for optimal anti-fibrinolytic effect,
      which is achievable with 1gm QID of oral administration. Large randomized
      controlled trials assessing the utility of tranexamic acid in various orthopedic
      surgeries did not show increased thromboembolic events. CONCLUSIONS: Tranexamic
      acid should be considered for patients with symptomatic nonarterial bleeding of
      the upper aerodigestive tract tumors. LEVEL OF EVIDENCE: 4.

PMID- 23553515
TI  - The use of the facial clinimetric evaluation scale as a patient-based grading
      system in Bell's palsy.
AB  - OBJECTIVES/HYPOTHESIS: The severity of Bell's facial palsy is monitored through
      physician-graded instruments, like the House-Brackmann or Sunnybrook Facial
      Grading System (FGS). These instruments primarily measure the degree of facial
      muscle impairment and its resulting asymmetry, but neglect the other functional
      aspects of facial disability. The aim of this study is therefore to compare the
      FGS with a patient-graded quality-of-life (QOL) instrument, Facial Clinimetric
      Evaluation Scale (FaCE). STUDY DESIGN: Prospective longitudinal study. METHODS:
      Twenty-one patients with newly diagnosed Bell's palsy were recruited. All
      patients received standard treatment with a corticosteroid. They were scored with
      the FGS at every visit, and they also completed the FaCE at baseline and when
      they recovered from their palsy. RESULTS: At presentation, there was a positive
      correlation between the FGS score and the total FaCE score (rho = 0.63, P =
      .002). However, when individual domains of the FaCE score were analyzed
      separately, the domains of facial comfort and lacrimal score did not have
      significant correlation with the FGS. Similarly, at the end of follow-up, the
      amount of improvement in FGS and the amount of improvement in the FaCE domains of
      facial comfort, lacrimal control, and social function showed insignificant and
      low correlation (P < .05). CONCLUSIONS: This is the first longitudinal study
      comparing scores on the FGS and FaCE in patients with Bell's palsy. Our findings
      suggest that without patient-based QOL assessments such as the FaCE, certain
      functional aspects of facial disability may be overlooked by physician-graded
      instruments, which focus on facial aesthetics. LEVEL OF EVIDENCE: 4.

PMID- 23553516
TI  - Preliminary investigation of absent nociceptive flexion reflex responses among
      more symptomatic women with fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS) is a widespread musculoskeletal pain condition with
      unclear physiologic mechanisms. The purpose of this investigation was to compare
      the responsiveness of nociceptive flexion reflex (NFR) pathways between women
      with and without FMS. A secondary purpose was to examine the influence of
      depression, fibromyalgia symptom severity, and cardiovascular health on NFR
      responses among women with FMS. Fifteen women with FMS and 14 healthy controls
      participated in an experimental session to assess NFR responses to sural nerve
      stimulation, resting mean arterial pressure (MAP) and heart rate (HR), and scores
      on the Beck Depression Inventory (BDI) and Fibromyalgia Impact Questionnaire
      (FIQ). NFR responses were successfully elicited from all healthy individuals, but
      only eight (53 %) of the women with FMS. These women did not differ in the
      minimum stimulus intensity required to elicit an NFR response compared to healthy
      controls (p >= 0.35). Further, these women had lower BDI (p = 0.04) and FIQ (p =
      0.02) scores compared to women with FMS from whom NFR responses could not be
      elicited. Resting HR was higher in both groups of women with FMS compared to
      healthy individuals (p < 0.05), and MAP was strongly associated with NFR
      thresholds only among women with FMS (r = 0.88, p < 0.01). Findings from this
      preliminary investigation suggest that NFR pathways are impaired in women who are
      more severely impacted by symptoms of depression and fibromyalgia, potentially
      due to desensitization of NFR pathways with chronic autonomic arousal.

PMID- 23553517
TI  - Relation of rheumatoid factor and anti-cyclic citrullinated peptide antibody with
      disease activity in rheumatoid arthritis: cross-sectional study.
AB  - To analyze the association of rheumatoid factor (RF) and anti-cyclic
      citrullinated peptide antibody (anti-CCP) with non-remission and with disease
      activity measures in rheumatoid arthritis (RA). Cross-sectional study of
      consecutive RA patients. Non-remission was defined as a disease activity score
      (DAS28) >= 2.6 at study enrollment. The Simplified Disease Activity Index (SDAI)
      and the Clinical Disease Activity Index (CDAI) were additionally measured. Serum
      titers of RF and anti-CCP were transformed into incremental levels (100/units)
      and log-transformed levels. Analysis of association with non-remission was done
      with logistic regression models, with and without adjustment for age, sex,
      disease duration, and corticoid use. Multiple regression models, raw and
      similarly adjusted, were used to measure the association of RF and anti-CCP with
      the disease activity measures. A total of 385 patients were included, of whom 286
      (74 %) were not in remission. Log-transformed RF level was associated with an
      increased risk of non-remission after adjustment (OR = 1.32, 95 % CI 1.04-1.67).
      This association was especially evident in patients with less than 10 years of
      disease duration (OR = 1.51, 95 % CI 1.15-1.99) and in those using steroids (OR =
      2.06, 95 % CI 1.22-3.48). Serum RF titers and log-transformed RF levels showed a
      small but significant association with DAS28 score (adjusted beta coefficients
      0.002 and 0.18, respectively; both p <= 0.01), but neither with SDAI or CDAI nor
      with anti-CCP antibody. : Log-transformed RF levels might be associated with non
      remission in RA, especially in patients with short disease duration or on
      steroids.

PMID- 23553518
TI  - Skin ulcer is a predictive and prognostic factor of acute or subacute
      interstitial lung disease in dermatomyositis.
AB  - The aim of this study was to determine whether skin ulcer can be used as a
      predictive and prognostic factor of acute/subacute interstitial lung disease
      (ILD) in Japanese patients with dermatomyositis (DM). We reviewed the medical
      records of 39 consecutive DM patients who were admitted to Tokyo Metropolitan
      Komagome Hospital from January 2000 to December 2009. The mean follow-up period
      was 63.9 +/- 51.6 months. Fifteen patients had acute/subacute ILD and 11 patients
      had chronic ILD. Seven out of 15 acute/subacute ILD led to respiratory failure
      and 3 of them died due to ILD. Skin ulcers were observed in 5 out of 15 patients
      with acute/subacute ILD (33.3 %) and in 2 out of 24 patients without
      acute/subacute ILD (8.3 %). The presence of skin ulcers was revealed to be a
      significant predictive factor for acute/subacute ILD among various parameters by
      multivariate analysis. In the 15 patients with acute/subacute ILD, the presence
      of skin ulcers was a significant poor prognostic factor (p = 0.0231) and the
      cumulative survival rate of patients with skin ulcers was 53.3 % for 12 months.
      Skin ulcer is a significant predictive and prognostic factor of acute/subacute
      ILD in patients with DM.

PMID- 23553519
TI  - Sexual maturation in Moroccan patients with juvenile idiopathic arthritis.
AB  - Abnormal puberty is often reported in children suffering from many chronic
      diseases. Juvenile idiopathic arthritis (JIA) is the most common joint disorder
      in developing children. The aim of this study was to assess sexual maturation of
      Moroccan children with JIA and to compare the development of secondary sexual
      characteristics in children with JIA to children in the general population. Forty
      children with JIA and 74 healthy controls were included in a cross-sectional
      study. The diagnosis of JIA was made according to the criteria of the
      International League of Association of Rheumatology. Every child was examined for
      the development of genitalia as per criteria given by Tanner. The children with
      JIA were also divided into 3 groups: pre-puberty (stage 1), puberty (stages 2-3)
      and post-puberty (stage 4-5), and the association between puberty and cumulative
      dose of steroids, disease duration, disease activity, height, weight and age was
      investigated. Forty children with JIA were included (22 male, 18 female); the
      mean of age of the patients was 11 +/- 4.23 years. Puberty in the patients (mean
      of tanner 2.43 +/- 1.36) was lower than controls (2.55 +/- 1.36). The prevalence
      of the children in prepuberty was of 15 (37.5 %) and 8 (20 %) in postpuberty. The
      prevalence of the children having a delayed puberty was of 6 (15 %) versus 1(1.4
      %) in healthy controls (p = 0.005). There was an association between dose of
      corticosteroids, age at the administration of corticosteroids and the delayed
      puberty in boys (p = 0.009). In addition, there was no significant association in
      both sex between this poor puberty and duration of JIA (p = 0.45 in boys and p =
      1.99 in girls) and its activity calculated by the DAS28 (p = 0.73 in boys and p =
      1). Our study suggests that the puberty is retarded in Moroccan patients with JIA
      comparing to healthy children and that the dose of corticosteroid and the age at
      its administration may contribute to delayed puberty in boys. 

PMID- 23553520
TI  - Poor accuracy of anti-citrulline antibody test in diagnosis of rheumatoid
      arthritis in Iran.

PMID- 23553521
TI  - Functional analyses of recombinant mouse hepcidin-1 in cell culture and animal
      model.
AB  - Hepcidin is a peptide hormone that plays an important role in iron metabolism. We
      have produced a recombinant mouse hepcidin-1 by using baculovirus expression
      system. Its expression yield was 25 MUg/ml when cell culture media were
      supplemented with a protease inhibitor cocktail. The recombinant mouse hepcidin-1
      and synthetic human hepcidin-25 had similar effects on reducing ferroportin
      expression in J774A cell line and in peritoneal macrophages. However, synthetic
      human hepcidin-25 was more efficient than recombinant mouse hepcidin-1 in
      reducing iron concentration in blood circulation (p < 0.01).

PMID- 23553522
TI  - Role of Wnt1 and Fzd1 in the spinal cord pathogenesis of amyotrophic lateral
      sclerosis-transgenic mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by chronic progressive degeneration of motor neurons resulting in
      muscular atrophy, paralysis, and ultimately death. We have investigated the
      expression of Wnt1 and Fzd1 in the spinal cords of SOD1G93A ALS transgenic mice,
      SOD1G93A-transfected N2a cells, and primary cultured astrocytes from SOD1G93A
      transgenic mice. In addition, we provided further insight into the role of Wnt1
      and Fzd1 in the pathogenesis of ALS transgenic mice and discuss the mechanisms
      underlying the Wnt signal pathway which may be useful in the treatment of ALS.
      The results indicate the involvement of Wnt1 and Fzd1 in the pathogenesis and
      development of ALS. 

PMID- 23553523
TI  - Use of dabigatran for periprocedural anticoagulation in patients undergoing
      catheter ablation for atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) for atrial fibrillation is associated
      with a transient increased risk of thromboembolic and hemorrhagic events. We
      hypothesized that dabigatran can be safely used as an alternative to continuous
      warfarin for the periprocedural anticoagulation in PVI. METHODS AND RESULTS: A
      total of 999 consecutive patients undergoing PVI were included; 376 patients were
      on dabigatran (150 mg), and 623 patients were on warfarin with therapeutic
      international normalized ratio. [corrected] Dabigatran was held 1 to 2 doses
      before PVI and restarted at the conclusion of the procedure or as soon as
      patients were transferred to the nursing floor. Propensity score matching was
      applied to generate a cohort of 344 patients in each group with balanced baseline
      data. Total hemorrhagic and thromboembolic complications were similar in both
      groups, before (3.2% versus 3.9%; P=0.59) and after (3.2% versus 4.1%; P=0.53)
      matching. Major hemorrhage occurred in 1.1% versus 1.6% (P=0.48) before and 1.2%
      versus 1.5% (P=0.74) after matching in the dabigatran versus warfarin group,
      respectively. A single thromboembolic event occurred in each of the dabigatran
      and warfarin groups. Despite higher doses of intraprocedural heparin, the mean
      activated clotting time was significantly lower in patients who held dabigatran
      for 1 or 2 doses than those on warfarin. CONCLUSIONS: Our study found no evidence
      to suggest a higher risk of thromboembolic or hemorrhagic complications with use
      of dabigatran for periprocedural anticoagulation in patients undergoing PVI
      compared with uninterrupted warfarin therapy.

PMID- 23553524
TI  - Amelioration of rhabdomyolysis-induced renal mitochondrial injury and apoptosis
      through suppression of Drp-1 translocation.
AB  - INTRODUCTION: Mitochondrial dysfunction plays an important role in acute kidney
      injury (AKI). Mitochondrial fission regulated by dynamin-related protein 1 (Drp
      1) impairs the function of the mitochondria and the survival of cells. This study
      was conducted to explore the effects of suppression of Drp-1 accumulation in the
      mitochondria, on mitochondrial function and renal tubular cell apoptosis in
      rhabdomyolysis (RM)-induced AKI. METHODS: An RM model was induced by
      intramuscular injection of glycerol in Sprague Dawley rats. Twenty-four and 48
      hours after intraperitoneal injections of mitochondrial division inhibitor 1
      (Mdivi-1), we observed the functions of the kidney, changes in pathology,
      expressions of Drp-1 in tubular tissues (by immunohistochemistry and Western
      blot) and accumulation of Drp-1 and mitofusin 2 in tubular mitochondria (by
      Western blot). Mitochondrial function (ATP and ROS) and tubular epithelial cell
      apoptosis (by TUNEL) were also measured. RESULTS: RM induced Drp-1 accumulation,
      decreased ATP production and increased ROS in mitochondria. With increasing
      cytochrome c expression, cell apoptosis increased, whereas kidney function
      decreased. These changes were time-dependent. At different time points, despite
      not significantly influencing the overall expression of Drp-1, Mdivi-1 suppressed
      the accumulation of Drp-1, inhibited the insertion of proapoptotic Bax in
      mitochondria and inhibited the release of cytochrome c, thus ameliorating cell
      apoptosis. CONCLUSIONS: To conclude, in RM-induced AKI, suppression of Drp-1
      accumulation in mitochondria favors the maintenance of mitochondrial function and
      reduces the apoptosis of tubular cells. Regulation of the mitochondrial fusion
      fission balance may offer a novel strategy for the prevention and treatment of RM
      induced AKI.

PMID- 23553525
TI  - Vascular access in older patients: an Italian survey.
AB  - BACKGROUND: The number of older patients starting ?hemodialysis is continuously
      increasing. The type of vascular access plays an important role in dialysis
      treatment, but it can be difficult to create in older patients. METHODS: This
      study compared vascular access survival rates and patient survival rates in older
      (>=65 years) and younger (<65 years) patients starting hemodialysis in 2 Italian
      hospitals in 2006-2008. RESULTS: The study enrolled 336 patients: 208 >=65 years
      and 128 <65 years of age. The vascular accesses used, in order of frequency, were
      102 distal arteriovenous fistulas (dAVFs) (49%), 55 midarm AVFs (pAVFs) (26%), 9
      arteriovenous grafts (AVGs) (4%) and 42 central venous catheters (CVCs) (20%) in
      the older patients, and 89 dAVFs (69%), 25 pAVFs (19%), 6 AVGs (5%) and 8 CVCs
      (6%) in the younger patients. Survival rates of fistula and catheter did not
      differ between the 2 groups. AVGs failed earlier (p = 0.02) in the older
      patients. On Cox analysis, age (hazard ratio [HR] = 1.073; p<0.001) and CVC (HR =
      4.152; p<0.001) increased the risk of death. CONCLUSION: A fistula is the gold
      standard for hemodialysis vascular access in older patients if judged
      appropriately.

PMID- 23553526
TI  - An uncommon presentation of an uncommon nephropathy: the karyomegalic
      interstitial nephritis.
AB  - Karyomegalic interstitial nephritis (KIN) is a rare and certainly underdiagnosed
      nephropathy. It is characterized by a peculiar histological picture of
      interstitial nephritis associated with the presence of hyperchromatic, abnormally
      enlarged nuclei of tubular epithelial cells. KIN has an uncertain etiology, but
      should be suspected in young patients in the second or third decade of life
      presenting with progressive renal failure, proteinuria and/or hematuria and a
      history of recurrent respiratory infections. In these cases, the diagnosis should
      be suspected and confirmed by a renal biopsy. Herein, we report a case of KIN
      with atypical clinical presentation in a young patient with progressive kidney
      failure without proteinuria or hematuria or history of recurrent respiratory
      infections. 

PMID- 23553527
TI  - Adiponectin is expressed and secreted by renal tubular epithelial cells.
AB  - BACKGROUND: Adiponectin (ADPN) is predominantly produced by adipose tissue, and
      high ADPN levels have been detected in patients affected by proteinuric
      glomerulonephritis. In this study we investigate whether human tubular epithelial
      cells express and secrete ADPN. METHODS: In human proximal tubular epithelial
      cells, HK-2, ADPN mRNA was evaluated by real-time PCR assay, while protein
      expression levels were measured by Western blot analysis and immunofluorescence
      assay. Moreover, renal ADPN distribution was assessed by immunohistochemical
      analysis of kidney biopsy samples from healthy patients. Finally, by ELISA, we
      measured ADPN concentrations in culture media of HK-2 cells treated with 10 ug/mL
      lipopolysaccharide (LPS). RESULTS: Our analyses revealed that HK-2 cells express
      ADPN both in terms of mRNA and protein. These results were confirmed by the
      observed cytoplasmatic HK-2 intense immunoreactivity for ADPN antibody and by
      immunohistochemical analysis showing a diffuse ADPN distribution in normal kidney
      tissue. Furthermore, we observed that tubular cells secrete ADPN in the basal
      condition and, more interestingly, that this secretion significantly increases
      (p<0.05) upon LPS treatment in a time-dependent manner. Finally,
      immunohistochemical analysis of kidney biopsy samples obtained from patients
      affected by membranous and rapidly progressive glomerulonephritis showed a
      similar pattern of ADPN staining to that observed in healthy controls.
      CONCLUSIONS: Our study demonstrates for the first time that renal tubular cells
      express and secrete ADPN, and their concentration increases upon inflammatory
      stimulus. These results suggest that in renal inflammatory diseases, tubular
      cells may contribute to the increase in circulating ADPN levels, triggering a
      feedback response in order to self-mitigate the inflammatory process.

PMID- 23553528
TI  - The epidemiology of atrial fibrillation in end-stage renal disease.
AB  - Accumulating evidence suggests that atrial fibrillation is highly prevalent among
      patients with end-stage renal disease. Physicians should be aware of this
      important association and implement meticulous monitoring of these patients,
      because the diagnosis of the arrhythmia is often challenging. In this
      comprehensive review we provide a concise overview of the current literature
      regarding the epidemiology of atrial fibrillation in end-stage renal disease, as
      well as the role of associated factors and predictors. 

PMID- 23553529
TI  - Analysis of vacuum ultraviolet electronic spectra of Ce3+ and Pr3+ ions in
      Ca9Lu(PO4)7: crystal-field calculations and simulation of optical spectra.
AB  - The 4f-5d excitation and emission spectra of Ce(3+) and Pr(3+) ions in
      Ca9Lu(PO4)7 as recently reported (2012 J. Phys.: Condens. Matter 24 385502) were
      further analyzed and simulated by employing the effective Hamiltonian model for
      the 4f(N) and 4f(N-1)5d electronic configurations of impurity lanthanide ions and
      the exchange charge model of crystal-field theory. The multi-site effect on the
      4f-5d transition spectra was explicitly discussed from the points of view of the
      local structure and site occupation ratios of lanthanide ions in Ca9Lu(PO4)7. An
      excellent agreement between the predicted and measured spectra confirms the
      validity of the performed calculations. Based on these energy level and intensity
      calculation results, the radiative lifetimes of the 5d-4f emissions of Ce(3+) and
      Pr(3+) ions have been modeled to show nearly independent temperature trends.
      Comparison with the measured lifetimes suggests the nonradiative relaxation
      process in this host is probably related to the intrinsic defect states. In
      addition to the studies of the 4f-5d transitions, a general theoretical scheme to
      calculate the lowest 4f-6s transition energy of the Ce(3+) ion was proposed for
      the first time on the basis of the ligand polarization model. The predicted 6s
      energy position of the Ce(3+) ion in Ca9Lu(PO4)7 is solid evidence corroborating
      our previous spectroscopic assignment.

PMID- 23553530
TI  - Frequency-dependent cell death by optical tweezers manipulation.
AB  - Optical tweezers were used to scan individual Chronic Myelogenous Leukemia cells
      to determine if the cell death depends on the scanning conditions. Although
      increasing the scanning frequency or amplitude means greater force applied to the
      cells, their effects on cell death are not a simple increasing trend, as observed
      in the optical microscopy. Indeed, cell death sharply increased at particular
      screening frequencies and amplitudes, whereas other frequencies or amplitudes
      were less detrimental. These results suggest that cell damage was more sensitive
      to certain scanning conditions, rather than simply high-applied forces.

PMID- 23553531
TI  - Effectiveness of the model for prenatal control of severe thalassemia.
AB  - OBJECTIVE: The aim of the research was to determine effectiveness of the model
      for prenatal control in reducing new cases of severe thalassemia. METHODS:
      Pregnant women at six tertiary centers were recruited to follow the model,
      consisting of (1) carrier screening using mean corpuscular volume (for alpha-thal
      1 and beta-thal) and CMU-E screen (for HbE trait), (2) carrier diagnosis, (3) the
      couples at risk were counseled and offered prenatal diagnosis, and (4)
      termination of affected pregnancy. All neonates were evaluated for thalassemia.
      RESULTS: Of the 12,874 recruited pregnancies, 7008 were valid for analysis. Of
      them, 281 couples were identified to be at risk, Of the 281, 58 affected fetuses
      were identified and 55 pregnancies were terminated, whereas three did not accept
      pregnancy termination. All 6727 neonates at no risk were proven to be unaffected.
      The model had sensitivity and positive predictive value of 100% and 20%,
      respectively. The model could detect all of affected fetuses. CONCLUSION: The
      model could prenatally identify affected fetuses with a detection rate and
      negative predictive value of 100%. The model was highly effective to prenatally
      detect affected fetuses with an acceptable false positive rate.

PMID- 23553532
TI  - The increasing role of otolaryngology in the management of surgical thyroid
      disorders.
AB  - OBJECTIVES/HYPOTHESIS: To determine trends in office visits and medical specialty
      seen for surgical diagnoses of the thyroid gland. STUDY DESIGN: A cross-sectional
      analysis of a national healthcare database. METHODS: From the National Ambulatory
      Medical Care Survey (NAMCS), all cases of surgical thyroid disorders (e.g.,
      benign neoplasm of thyroid gland, malignant neoplasm of thyroid gland,
      multinodular goiter) were extracted for 2 calendar year cohorts: 1995 to 1999 and
      2005 to 2009. In addition to demographic information, the medical specialty of
      the health care provider seen was extracted. Comparisons were conducted for the
      proportion of surgical thyroid cases seen between general surgeons and
      otolaryngologists for the respective cohorts. RESULTS: In the 1995 to 1999
      cohort, there were a total of 107 +/- 13 thousand outpatient visits annually to
      either general surgery or otolaryngology for surgical thyroid conditions. Among
      these, 62.7 +/- 8.4 thousand visits (58.3 +/- 5.6%) were seen by general surgery
      versus 44.8 +/- 9.1 thousand (41.7 +/- 5.6%) seen by otolaryngology. In
      comparison, in the 2005 to 2009 cohort, there were 218 +/- 29 thousand visits
      annually for surgical thyroid conditions. Among these, 88.4 +/- 17 thousand (40.5
      +/- 5.4%) were seen by general surgery versus 130 +/- 21 thousand (59.5 +/- 5.4%)
      seen by otolaryngology. The increase in proportion of surgical thyroid patients
      seen by otolaryngology in the second 5 year cohort was statistically significant
      (P = 0.032, chi-square). CONCLUSIONS: There is a national trend in the United
      States toward otolaryngologists seeing an increasing majority proportion of
      increasingly prevalent surgical thyroid conditions. These data objectively
      confirm the perceived increasing role of otolaryngologists in the management of
      surgical thyroid disorders on a national level.

PMID- 23553533
TI  - Development of 7TM receptor-ligand complex models using ligand-biased, semi
      empirical helix-bundle repacking in torsion space: application to the agonist
      interaction of the human dopamine D2 receptor.
AB  - Prediction of 3D structures of membrane proteins, and of G-protein coupled
      receptors (GPCRs) in particular, is motivated by their importance in biological
      systems and the difficulties associated with experimental structure
      determination. In the present study, a novel method for the prediction of 3D
      structures of the membrane-embedded region of helical membrane proteins is
      presented. A large pool of candidate models are produced by repacking of the
      helices of a homology model using Monte Carlo sampling in torsion space, followed
      by ranking based on their geometric and ligand-binding properties. The trajectory
      is directed by weak initial restraints to orient helices towards the original
      model to improve computation efficiency, and by a ligand to guide the receptor
      towards a chosen conformational state. The method was validated by construction
      of the beta1 adrenergic receptor model in complex with (S)-cyanopindolol using
      bovine rhodopsin as template. In addition, models of the dopamine D2 receptor
      were produced with the selective and rigid agonist (R)-N-propylapomorphine ((R)
      NPA) present. A second quality assessment was implemented by evaluating the
      results from docking of a library of 29 ligands with known activity, which
      further discriminated between receptor models. Agonist binding and recognition by
      the dopamine D2 receptor is interpreted using the 3D structure model resulting
      from the approach. This method has a potential for modeling of all types of
      helical transmembrane proteins for which a structural template with sequence
      homology sufficient for homology modeling is not available or is in an incorrect
      conformational state, but for which sufficient empirical information is
      accessible.

PMID- 23553534
TI  - Effect of intravenous zanamivir on cardiac repolarization.
AB  - STUDY OBJECTIVE: To assess the effect of a therapeutic and supratherapeutic
      intravenous dose of the neuraminidase inhibitor zanamivir on QT and rate
      corrected QT intervals. DESIGN: Randomized, placebo-controlled, single-dose, four
      period, balanced crossover study. SETTING: Clinical research unit. SUBJECTS:
      Forty healthy adults were randomized to receive intravenous zanamivir at two dose
      levels, oral moxifloxacin, and placebo; 38 subjects completed all four study
      treatments. INTERVENTION: Subjects were randomized to receive a single
      intravenous dose of zanamivir 600 mg (therapeutic dose) with oral moxifloxacin
      placebo, a single intravenous dose of zanamivir 1200 mg (supratherapeutic dose)
      with oral moxifloxacin placebo, oral moxifloxacin 400 mg (positive control) with
      intravenous zanamivir placebo, or intravenous zanamivir placebo with oral
      moxifloxacin placebo. Subjects crossed over to all other treatments, with each
      treatment separated by a 7-day washout period. MEASUREMENTS AND MAIN RESULTS:
      Zanamivir pharmacokinetics were dose proportional; the pharmacokinetic exposure
      from zanamivir 1200 mg was 2 times higher than that from 600 mg, the maximum dose
      under clinical evaluation. For both 600-mg and 1200-mg doses of intravenous
      zanamivir, the upper limit of the 90% confidence interval (CI) for the placebo
      adjusted mean change from baseline of the QT interval corrected for heart rate
      using Fridericia's formula (DeltaDeltaQTcF) was less than 10 msec at all time
      points. The sensitivity of the study to detect modest increases in QT interval
      was established with the positive control, moxifloxacin. The maximum
      DeltaDeltaQTcF value for zanamivir 1200 mg was 1.73 msec (90% CI -0.40 to 3.87
      msec), which was observed within 30 minutes after dosing, and 11.21 msec (90% CI
      8.81-13.60) for moxifloxacin, observed at 4 hours after dosing. No relationship
      was observed between zanamivir serum concentration and DeltaDeltaQTcF. Zanamivir
      was generally well tolerated, with very few adverse events; none were serious or
      severe. CONCLUSION: Intravenous zanamivir does not affect cardiac repolarization.
      Accordingly, treatment with intravenous zanamivir does not require additional
      cardiac monitoring beyond the standard of care.

PMID- 23553535
TI  - pH-dependent effect of pectinase secretion in Penicillium griseoroseum
      recombinant strains.
AB  - A number of parameters, including culture medium pH, affect growth and enzyme
      production by microorganisms. In the present study, the production and secretion
      of pectin lyase (PL) and polygalacturonase (PG) by recombinant strains of
      Penicillium griseoroseum cultured in mineral-buffered media (MBM; initial pH 6.8)
      and mineral-unbuffered medium (MUM; initial pH 6.3) were evaluated. Under these
      culture conditions, no change in the transcriptional levels of plg1 and pgg2 was
      observed. However, the levels of secreted total protein ranged from 7.80 +/- 1.1
      to 3.25 +/- 1.50 ug ml(-1) in MBM and MUM, respectively, and were evaluated by
      SDS-PAGE. PL and PG enzymatic activities decreased 6.4 and 3.6 times,
      respectively, when P. griseoroseum was cultivated under acidic pH conditions
      (MUM). Furthermore, differences were observed in the hypha and mycelium
      morphology. These findings suggest that acidic growing conditions affect PL and
      PG secretion, even though the transcription and translation processes are
      successful. The data obtained in this study will help to establish optimal
      culture conditions that increase production and secretion of recombinant proteins
      by filamentous fungi. 

PMID- 23553536
TI  - Overexpression of sirtuin 6 suppresses inflammatory responses and bone
      destruction in mice with collagen-induced arthritis.
AB  - OBJECTIVE: Sirtuin 6 (SIRT-6) is an NAD(+) -dependent deacetylase and mono-ADP
      ribosyltransferase. It is known to interfere with the NF-kappaB signaling pathway
      and thereby has an antiinflammatory function. Due to the central role of NF
      kappaB in rheumatoid arthritis (RA) development, we undertook this study to test
      our hypothesis that SIRT-6 could have antiarthritic effects. METHODS: An
      adenovirus containing SIRT-6 complementary DNA (Ad-SIRT6) was used to deliver
      SIRT-6 to human RA fibroblast-like synoviocytes in vitro as well as to mice with
      collagen-induced arthritis (CIA) in vivo via bilateral intraarticular injections
      into the ankle joints. RESULTS: In vitro experiments demonstrated that SIRT-6
      overexpression suppressed NF-kappaB target gene expression induced by tumor
      necrosis factor alpha. SIRT-6 overexpression inhibited osteoclast differentiation
      induced by macrophage colony-stimulating factor and RANKL in bone marrow-derived
      macrophages. Mice with CIA had an increased incidence of disease and developed
      arthritis in the hind paws. In contrast, mice injected with Ad-SIRT6 showed
      attenuated severity of arthritis based on clinical scores, hind paw thickness,
      and radiographic and pathologic findings. Moreover, the injection of Ad-SIRT6
      down-regulated local and systemic levels of proinflammatory cytokines. After
      induction of CIA, mice injected with Ad-SIRT6 showed significantly decreased
      arthritis severity, from the onset of clinical signs to the end of the study.
      CONCLUSION: These results suggest that blocking the NF-kappaB pathway by SIRT-6
      in rheumatoid joints reduces both the inflammatory response and tissue
      destruction. Therefore, the development of an immunoregulatory strategy based on
      SIRT-6 may have therapeutic potential for the treatment of RA.

PMID- 23553537
TI  - Panel forum on multiple comparison procedures: a commentary from a complex trial
      design and analysis plan.
AB  - Motivated by a complex study design aiming at a definitive evidential setting, a
      panel forum among academia, industry, and US regulatory statistical scientists
      was held at the 7th International Conference on Multiple Comparison Procedures
      (MCP) to comment on the multiplicity problem. It is well accepted that studywise
      or familywise, type I error rate control is the norm for confirmatory trials.
      But, it is an uncharted territory regarding the criteria beyond a single
      confirmatory trial. The case example describes a Phase III program consisting of
      two placebo-controlled multiregional clinical trials identical in design intended
      to support registration for treatment of a chronic condition in the lung. The
      case presents a sophisticated multiplicity problem in several levels: four
      primary endpoints, two doses, two studies, two regions with different regulatory
      requirements, one major protocol amendment on the original statistical analysis
      plan, which the panelists had a chance to study before the forum took place.
      There were differences in professional perspectives among the panelists laid out
      by sections. Nonetheless, irrespective of the amendment, it may be arguable
      whether the two studies are poolable for the analysis of two primary endpoints
      prespecified. How should the study finding be reported in a scientific journal if
      one health authority approves while the other does not? It is tempting to address
      the Phase III program level multiplicity motivated by the increasing complexity
      of the partial hypotheses framework posed that are across studies. A novel
      thinking of the MCP procedures beyond individual-study level (studywise or
      familywise as predefined) and across multiple-study level (experimentwise and
      sometimes programwise) will become an important research problem expected to face
      with scientific and regulatory challenges.

PMID- 23553539
TI  - Diastolic dysfunction and arterial stiffness: the chicken or the egg.

PMID- 23553538
TI  - Impaired regeneration in LGMD2A supported by increased PAX7-positive satellite
      cell content and muscle-specific microrna dysregulation.
AB  - INTRODUCTION: Recent in vitro studies suggest that CAPN3 deficiency leads
      initially to accelerated myofiber formation followed by depletion of satellite
      cells (SC). In normal muscle, up-regulation of miR-1 and miR-206 facilitates
      transition from proliferating SCs to differentiating myogenic progenitors.
      METHODS: We examined the histopathological stages, Pax7 SC content, and muscle
      specific microRNA expression in biopsy specimens from well-characterized LGMD 2A
      patients to gain insight into disease pathogenesis. RESULTS: Three distinct
      stages of pathological changes were identified that represented the continuum of
      the dystrophic process from prominent inflammation with necrosis and regeneration
      to prominent fibrosis, which correlated with age and disease duration. Pax7
      positive SCs were highest in the fibrotic group and correlated with down
      regulation of miR-1, miR-133a, and miR-206. CONCLUSIONS: These observations, and
      other published reports, are consistent with microRNA dysregulation leading to
      inability of Pax7-positive SCs to transit from proliferation to differentiation.
      This results in impaired regeneration and fibrosis.

PMID- 23553540
TI  - Effectiveness of golimumab in clinical management of patients with rheumatoid
      arthritis.
AB  - BACKGROUND AND OBJECTIVES: Limited data are available regarding the use of
      golimumab (100 mg) every 4 weeks, with or without methotrexate (MTX). The aim of
      this retrospective analysis was to evaluate the effectiveness and safety of
      golimumab following usual clinical practice in Japanese patients with rheumatoid
      arthritis (RA) according to the recommendations given in the Japanese package
      insert. PATIENTS AND METHODS: Japanese RA patients with moderate-to-high disease
      activity, according to the 28-joint disease activity score based on C-reactive
      protein (DAS28-CRP) criteria, despite treatment with MTX or another biological
      agent, were enrolled. Patients were assigned to 50 mg golimumab plus MTX or 100
      mg golimumab monotherapy every 4 weeks for 24 weeks. All patients were given MTX
      if it was not contraindicated. The primary endpoint was the proportion of
      patients achieving clinical remission (defined as a DAS28-CRP <2.3 or a
      simplified disease activity index [SDAI] score <3.3) at 24 weeks. RESULTS: Most
      patients received combined 50 mg golimumab plus MTX (41/43). In these patients,
      the primary endpoint, clinical remission, was attained in 83 % of patients
      according to DAS28-CRP criteria (p < 0.001) and 69 % according to SDAI criteria
      (p < 0.001) by week 24. Adverse events were reported in 11.6 % of patients
      receiving golimumab. CONCLUSIONS: Golimumab (50 mg) plus MTX effectively reduced
      the signs and symptoms of RA and was generally well tolerated in patients with an
      inadequate response to MTX and other biological agents.

PMID- 23553541
TI  - Naringin promotes osteoblast differentiation and effectively reverses ovariectomy
      associated osteoporosis.
AB  - BACKGROUND: Osteoporosis is a common pathological condition that influences 20 %
      of women over 50 years of age. This condition decreases bone strength and
      increases the risk of bone fracture. Naringin is a major flavonoid found in
      grapefruit and an active compound extracted from a Chinese herbal medicine
      (Rhizoma Drynariae). Studies have shown that naringin possesses many
      pharmacological effects. The current study evaluated the influence of naringin on
      osteoblastic cell differentiation and proliferation, and assessed its therapeutic
      effects on a rat osteoporosis model. METHOD: The proliferation, differentiation,
      and function of rat bone marrow stromal cells (BMSCs) were determined following
      treatment with various concentrations of naringin. Ovariectomy (OVX)-induced
      osteoporotic rats were orally administered naringin daily at low, medium, and
      high dosages, while a control group received PBS for 2 months. Femoral X-ray
      images and microCT scans were used for bone mineral density (BMD) and BV/TV (bone
      volume/total volume) analyses, and histological assessments of left tibiae were
      employed to check for changes in trabecular thickness (Tb.Th) and trabecular
      space (Tb.Sp) in the groups. RESULTS: Naringin was effective at enhancing the
      proliferation and osteogenic differentiation of BMSCs, and a concentration of 10
      MUg/ml prompted the highest levels of osteocalcin expression among the in vitro
      study groups. There appeared to be a delayed response pattern of BMSCs to the
      naringin treatment. Naringin also effectively reversed OVX-induced bone loss via
      increasing BMD, bone volume, and trabecular thickness. The medium dose (300
      mg/kg) appeared to be the optimal dosage for delivering satisfactory therapeutic
      effects. CONCLUSION: Naringin promotes the proliferation and differentiation of
      BMSCs, and increases osteocalcin expression. Naringin also effectively reverses
      ovariectomy-induced osteoporosis in rats. The study suggests that naringin
      administration may represent an effective treatment for osteoporosis.

PMID- 23553542
TI  - The role of internal fixation for long bone metastasis prior to impending
      fracture: an experimental model.
AB  - BACKGROUND: Patients with long bone metastasis have many therapeutic options,
      including surgery. However, the appropriate time for surgical intervention and
      the use of internal fixation prior to impending fracture remains controversial.
      The purpose of this study was to establish a long bone metastatic model with
      internal fixation, and to determine whether prophylactic internal fixation for
      long bone metastasis prior to impending fracture would affect bone destruction,
      tumor progression, and mortality. MATERIALS AND METHODS: We implanted VX2 tumor
      cells into the tibiae of 45 rabbits divided equally into three groups: internal
      fixation, control, and sham groups. Rabbits were monitored by X-ray and computed
      tomography, and blood serum levels were examined every 2 weeks. RESULTS: Computed
      tomography data revealed significantly higher bone destruction in rabbit tibiae
      in the sham and control groups compared with those in the fixation group; there
      were volumetric bone losses of 0.2, 0.4, and 2.3% in the fixation, sham, and
      control groups, respectively, at 3 weeks, which increased to 1.2, 2.5, and 6.1%
      at 5 weeks. Rabbits in the fixation group showed significantly prolonged survival
      (64.5 +/- 13.5 days) in comparison with rabbits in the sham group (50.3 +/- 11.6
      days) and control group (38.2 +/- 4.9 days). CONCLUSION: Our results suggest that
      prophylactic internal fixation may hinder bone destruction and tumor progression,
      thus extending the survival period for patients with long bone metastasis.

PMID- 23553543
TI  - Effect of torrefaction for the pretreatment of rice straw for ethanol production.
AB  - BACKGROUND: Rice straw is an attractive lignocellulosic material for ethanol
      production, since it is one of the most abundant renewable resources. It
      generally has high cellulose and hemicellulose contents that can be readily
      hydrolysed into sugars for subsequent ethanol fermentation. The pretreatment
      method plays an important role in increasing the efficiency of enzymatic
      saccharification, thereby making the whole process economically viable.
      Torrefaction is an appropriate pretreatment technique for enhancing the enzymatic
      reaction and subsequent ethanol production. RESULTS: The effects of two important
      parameters, i.e. residence time (20, 40 and 60 min) and temperature (160, 180,
      200, 220, 240 and 260  degrees C), were studied under an inert atmosphere. The
      highest yield of 351 +/- 5.49 mg g(-1) total sugars was obtained after
      torrefaction treatment at 220  degrees C for 40 min, representing a 60.68%
      increase compared with the untreated sample. Based on ethanol studies conducted
      on rice straw, this estimated quantity of sugars could produce 150 +/- 2.40 mg g(
      1) ethanol, a 50.67% increase compared with the untreated sample under anaerobic
      conditions. The fermentation rate was enhanced by adding 0.4 mmol L(-1) benzoic
      acid. CONCLUSION: The use of this waste material could reduce competition with
      food materials for ethanol production. It can be considered as an alternative
      sustainable waste management option.

PMID- 23553544
TI  - Clinical dilemmas and a review of strategies to manage drug shortages.
AB  - OBJECTIVE: The objectives of this article are to review the clinical implications
      of drug shortages highlighting patient safety, sedation, and oncology and
      introduce an expanded phase approach for the management of drug shortages. DATA
      SOURCES: Literature retrieval was accessed through a PubMed search of English
      language sources from January 1990 through April 2012 using the medical subject
      heading pharmaceutical preparations/supply and distribution and the general
      search term drug shortages. STUDY SELECTION AND DATA EXTRACTION: All original
      prospective and retrospective studies, peer-reviewed guidelines, consensus
      statements, and review articles were evaluated for inclusion. Relevance was
      determined considering the therapeutic class, focus on drug shortages, and
      manuscript type. DATA SYNTHESIS: The increased number of drug shortages has
      created significant challenges for health care providers. Two particularly
      vulnerable populations are critically ill and oncology patients. A lack of
      therapeutic alternatives in critically ill patients may impact patient safety as
      well as treatment outcomes. Similarly, a chemotherapy agent in short supply may
      contribute to adverse outcomes in oncology patients. CONCLUSIONS: The mounting
      number of drug shortages has created a health care crisis, requiring changes in
      management strategies as well as clinical practice. The expanded phased approach
      outlined here provides a consistent, systematic approach for the management of
      drug shortages.

PMID- 23553545
TI  - Igniting the fire within: a primer on political advocacy for pharmacy
      professionals.
AB  - Due to the expanding role of pharmacy in health care, it is imperative that
      pharmacy professionals work together to advocate for the profession. An English
      language only literature search was conducted of the PubMed and Medline databases
      using the key words advocacy, grassroots, political action committee, lobbying,
      politics, political action, legislation, letter writing, pharmacy, pharmacist,
      Capitol Hill. Up-to-date information regarding pharmacy-specific advocacy was
      limited and difficult to locate. Information from the literature search was
      supplemented with interviews of professionals actively engaged in advocacy,
      personal experience, and Web sites of national pharmacy organizations. This
      primer ignites the fire for political advocacy within pharmacy professionals by
      reinforcing the significant impact that advocacy has on the profession and by
      providing information on how to become involved. The primer provides a
      comprehensive "pocket guide" of resources combined into an easy-to-use reference
      for pharmacy professionals and outlines a structured approach on how to become a
      pharmacy advocate, ranging from a minimal level of involvement to master
      political activist, and to promote interest among pharmacy professionals to
      become more engaged with advocacy. Even a small act of advocacy or volunteerism
      can transform a spark into a raging fire.

PMID- 23553546
TI  - The eye of the self: precuneus volume and visual perspective during
      autobiographical memory retrieval.
AB  - Visual perspective (i.e. first-person versus third-person perspective) during
      autobiographical memory (AM) retrieval plays a role in both emotional regulation
      and self-related processes. However, its neural underpinnings remain mostly
      unexplored. Visual perspective during AM retrieval was assessed in two
      independent datasets of 45 and 20 healthy young adults with two different AM
      retrieval tasks. Diffeomorphic anatomical registration using exponentiated lie
      algebra and voxel-based morphometry were used to assess individual differences in
      the precuneus grey matter volume. The spontaneous tendency to recall memories
      from a first-person perspective was positively correlated with the right
      precuneus volume among the two independent datasets. Whole-brain analyses
      revealed that these results were relatively specific to the anterior part of the
      right precuneus. Our results provide first evidence for the role of the precuneus
      in egocentric spatial processing in the context of AM retrieval among healthy
      subjects. 

PMID- 23553547
TI  - Changes in cerebral morphometry and amplitude of low-frequency fluctuations of
      BOLD signals during healthy aging: correlation with inhibitory control.
AB  - Aging is known to be associated with changes in cerebral morphometry and in
      regional activations during resting or cognitive challenges. Here, we
      investigated the effects of age on cerebral gray matter (GM) volumes and
      fractional amplitude of low-frequency fluctuation (fALFF) of blood oxygenation
      level-dependent signals in 111 healthy adults, 18-72 years of age. GM volumes
      were computed using voxel-based morphometry as implemented in Statistical
      Parametric Mapping, and fALFF maps were computed for task-residuals as described
      in Zhang and Li (Neuroimage 49:1911-1918, 2010) for individual participants.
      Across participants, a simple regression against age was performed for GM volumes
      and fALFF, respectively, with quantity of recent alcohol use as a covariate. At
      cluster level p < 0.05, corrected for family-wise error of multiple comparisons,
      GM volumes declined with age in prefrontal/frontal regions, bilateral insula, and
      left inferior parietal lobule (IPL), suggesting structural vulnerability of these
      areas to aging. FALFF was negatively correlated with age in the supplementary
      motor area (SMA), pre-SMA, anterior cingulate cortex, bilateral dorsal lateral
      prefrontal cortex (DLPFC), right IPL, and posterior cingulate cortex, indicating
      that spontaneous neural activities in these areas during cognitive performance
      decrease with age. Notably, these age-related changes overlapped in the
      prefrontal/frontal regions including the pre-SMA, SMA, and DLPFC. Furthermore, GM
      volumes and fALFF of the pre-SMA/SMA were negatively correlated with the stop
      signal reaction time, in accord with our earlier work. Together, these results
      describe anatomical and functional changes in prefrontal/frontal regions and how
      these changes are associated with declining inhibitory control during aging. 

PMID- 23553548
TI  - Epitaxial strain induced magnetic transitions and phonon instabilities in
      tetragonal SrRuO3.
AB  - Using density-functional theory calculations, we investigate the magnetic as well
      as the dynamical properties of tetragonal SrRuO3 (SRO) under the influence of
      epitaxial strain. It is found that both tensile and compressive strain in the xy
      plane can induce an abrupt change in the magnetic moment of the Ru atom. In
      particular, under an in-plane compressive strain of ~4%, a ferromagnetic to
      nonmagnetic transition is induced, whereas for a tensile strain larger than 3%,
      the magnetic moment of Ru drops gradually with increase of the strain, exhibiting
      a weak ferromagnetic state. We find that these magnetic transitions can be
      qualitatively explained by the Stoner model. In addition, frozen-phonon
      calculations at the Gamma point and phonon dispersion calculations reveal that
      structural instabilities can occur under both compressive and tensile strain.
      These instabilities are very similar to those of the ferroelectric perovskite
      oxides, even though SRO remains metallic in the range we studied. This might have
      an influence on the physical properties of oxide supercells having SRO as a
      constituent.

PMID- 23553549
TI  - Lack of effectiveness of sodium bicarbonate in preventing kidney injury in
      patients undergoing cardiac surgery: a randomized controlled trial.
AB  - STUDY OBJECTIVE: Because alkalinization of the renal tubules can theoretically
      protect against the mechanisms of acute kidney injury, we sought to determine
      whether a sodium bicarbonate infusion can prevent acute kidney injury after
      cardiac surgery. DESIGN: Prospective, randomized, double-blind, controlled trial.
      SETTING: Cardiac surgery service in a community hospital. PATIENTS: Ninety-two
      patients with stage 3 or higher chronic kidney disease who underwent cardiac
      surgery using cardiopulmonary bypass. INTERVENTION: Forty-eight patients received
      a perioperative intravenous infusion of 0.9% sodium chloride 154 mEq/L, and 44
      patients received an infusion of sodium bicarbonate infusion 150 mEq/L in 5%
      dextrose solution; the infusions were started 1 hour preoperatively and continued
      for 6 hours after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was the development of any stage of acute kidney injury within 5
      days after surgery as defined by the Acute Kidney Injury Network criteria. No
      statistically significant difference in the primary outcome was noted between the
      two groups: 32% in the bicarbonate group versus 42% in the sodium chloride group
      (p=0.12). Likewise, no significant differences in the 30-day hospital mortality
      rate or other adverse outcomes were noted between the two groups. CONCLUSION: A
      perioperative infusion of sodium bicarbonate did not reduce the rate of acute
      kidney injury or adverse outcomes in patients with chronic kidney disease who
      underwent cardiac surgery.

PMID- 23553550
TI  - Na+/H+ exchange is inactivated during mouse oocyte meiosis, facilitating glycine
      accumulation that maintains embryo cell volume.
AB  - The coupled action of the Na(+)/H(+) exchanger NHE1 and the HCO3(-)/Cl(-)
      exchanger AE2 constitutes the principal mechanism for acute correction of
      decreased cell volume in mammalian somatic cells, while, when acting separately,
      they regulate intracellular pH. It was previously found that AE2 becomes
      inactivated during meiosis in mouse oocytes. Similarly, NHE1 activity stimulated
      by intracellular acidosis was present in preovulatory germinal vesicle stage (GV)
      mouse oocytes and then decreased during meiotic maturation. In contrast, NHE1
      activity stimulated by decreased cell volume was low in GV oocytes but became
      active during meiotic maturation as the oocyte detached from the zona pellucida.
      It then decreased again in mature eggs similar to activity stimulated by
      acidosis. The subcellular localization of NHE1 was investigated with YFP-tagged
      NHE1. Exogenous NHE1 expressed in GV oocytes localized to the plasma membrane and
      resulted in increased Na(+)/H(+) exchanger activity, but only when co-expressed
      with calcineurin homologous protein 1 (CHP1). When oocytes expressing functional
      NHE1 were matured to eggs, however, membrane localization of NHE1 and Na(+)/H(+)
      exchanger activity were lost. It was unknown why NHE1 and AE2 activities are
      suppressed during meiotic maturation. Maintenance of cell volume in
      preimplantation embryos requires glycine accumulation via the GLYT1 transporter,
      a process unique to eggs and early embryos that is initiated during meiotic
      maturation. When NHE1 and AE2 activities were maintained in GV oocytes by
      exogenous expression, glycine accumulation was inhibited. We propose that NHE1
      mediated acute cell volume regulation is inactivated during meiotic maturation to
      allow preferential accumulation of glycine in eggs.

PMID- 23553551
TI  - Environmentally safe treatment of black liquor with Comamonas sp. B-9 under high
      alkaline conditions.
AB  - The strain Comamonas sp. B-9 was isolated from steeping fluid of erosive bamboo
      slips derived from Kingdom Wu during the Three-Kingdoms Dynasty of ancient China
      (A.D. 220-280). It could be used to treat black liquor (BL) with high-alkaline pH
      and with an initial chemical oxygen demand (COD) of 18,000-25,000 mg L(-1) ,
      without the addition of other carbon and nitrogen sources. The results revealed
      that Comamonas sp. B-9 was capable of reducing the COD, color, and lignin content
      of BL by up to 56.8, 35.3, and 43.5%, respectively. High levels of laccase,
      manganese peroxidase, cellulase, and xylanase enzymatic activities were also
      observed, and these enzymes could play an important role in the biotreatment of
      BL. Further, GC-MS analysis showed that most of the compounds detected in BL
      after biotreatment with Comamonas sp. B-9 were diminished, while 4-methyl
      benzaldehyde, 3,4,5-trihydroxybenzoic acid ethyl ester, and 4-hydroxy-3,5
      dimethoxy benzaldehyde were produced as metabolites. The presented results
      indicate that Comamonas sp. B-9 has potential application for the treatment of
      wastewaters from pulp and paper processing with high COD load under high-alkaline
      conditions. 

PMID- 23553553
TI  - Current treatment of active infective endocarditis with brain complications.
AB  - We describe the optimal timing of surgery in active infective endocarditis
      patients with brain complications. (1) Non-hemorrhagic infarction: elective
      surgery has been recommended in patients with non-hemorrhagic infarction.
      However, the timing is changing to an earlier phase. Recent studies have shown
      that silent brain embolism and small-size infarction (15-20 mm) without coma can
      be operated safely without delay. On the other hand, in patients with large non
      hemorrhagic infarction with impaired consciousness, early surgery is not
      recommended. (2) Non-ruptured infectious intracranial aneurysm: treatment
      strategies for patients with infectious aneurysms without rupture remain
      controversial. However, the treatments are generally as follows. If the
      intracranial aneurysm without rupture decreases in size by administration of
      effective antibiotics, neurosurgery will not be required and cardiac surgery can
      be prioritized without delay. When the aneurysm without rupture enlarges and
      changes its morphology, neurosurgery or endovascular surgery should be
      prioritized to prevent its rupture. (3) Hemorrhagic stroke: this type is
      classified into primary intra-cerebral hemorrhage due to simple necrotic
      arteritis, hemorrhagic transformation of ischemic infarcts, and rupture of
      intracranial infectious aneurysms. Among these, primary intracerebral hemorrhage
      is the most frequently observed. In patients with the primary intracerebral
      hemorrhage, surgery must be postponed for at least 4 weeks to prevent
      exacerbation of bleeding. In patients with ruptured infectious aneurysm,
      neurosurgery or endovascular surgery is performed initially and cardiac surgery
      should be postponed at least 2-3 weeks.

PMID- 23553554
TI  - Limited distal sialodochotomy to facilitate sialendoscopy of the submandibular
      duct.

PMID- 23553552
TI  - Noninvasive fetal genome sequencing: a primer.
AB  - We recently demonstrated whole genome sequencing of a human fetus using only
      parental DNA samples and plasma from the pregnant mother. This proof-of-concept
      study demonstrated how samples obtained noninvasively in the first or second
      trimester can be analyzed to yield a highly accurate and substantially complete
      genetic profile of the fetus, including both inherited and de novo variation.
      Here, we revisit our original study from a clinical standpoint, provide an
      overview of the scientific approach, and describe opportunities and challenges
      along the path toward clinical adoption of noninvasive fetal whole genome
      sequencing.

PMID- 23553555
TI  - Physiology and toxicology of hormone-disrupting chemicals in higher plants.
AB  - Higher plants are exposed to natural environmental organic chemicals, associated
      with plant-environment interactions, and xenobiotic environmental organic
      chemicals, associated with anthropogenic activities. The effects of these
      chemicals result not only from interaction with metabolic targets, but also from
      interaction with the complex regulatory networks of hormone signaling. Purpose
      designed plant hormone analogues thus show extensive signaling effects on gene
      regulation and are as such important for understanding plant hormone mechanisms
      and for manipulating plant growth and development. Some natural environmental
      chemicals also act on plants through interference with the perception and
      transduction of endogenous hormone signals. In a number of cases, bioactive
      xenobiotics, including herbicides that have been designed to affect specific
      metabolic targets, show extensive gene regulation effects, which are more in
      accordance with signaling effects than with consequences of metabolic effects.
      Some of these effects could be due to structural analogies with plant hormones or
      to interference with hormone metabolism, thus resulting in situations of hormone
      disruption similar to animal cell endocrine disruption by xenobiotics. These
      hormone-disrupting effects can be superimposed on parallel metabolic effects,
      thus indicating that toxicological characterisation of xenobiotics must take into
      consideration the whole range of signaling and metabolic effects. Hormone
      disruptive signaling effects probably predominate when xenobiotic concentrations
      are low, as occurs in situations of residual low-level pollutions. These hormone
      disruptive effects in plants may thus be of importance for understanding cryptic
      effects of low-dosage xenobiotics, as well as the interactive effects of mixtures
      of xenobiotic pollutants.

PMID- 23553558
TI  - Use of topical nasal therapies in the management of chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: To determine whether the use of topical nasal therapies
      with saline alone and in combination with antibiotics, antifungals, or
      corticosteroids is effective in the treatment of patients with chronic
      rhinosinusitis (CRS). DATA SOURCES: A systematic literature search was performed
      utilizing the MEDLINE database (1966 to May 2012), EMBASE database (1980 to May
      2012), and the Cochrane Central Register of Controlled Trials. REVIEW METHODS:
      Electronic databases were searched by three otolaryngologists. Studies on five
      major categories of topical nasal therapies searched included saline (hypotonic,
      isotonic and hypertonic); topical antibiotics, topical steroids, and topical
      antifungals were obtained. Randomized controlled trials and meta-analyses of
      randomized controlled trials were included. RESULTS: Sixteen randomized
      controlled trials were identified examining topical saline (hypertonic or
      isotonic) in CRS patients. Two randomized controlled trials were found studying
      the effect of topical antibiotics in patients with CRS. Four randomized
      controlled trials were identified studying topical antifungal treatment for CRS.
      Twenty-five randomized controlled trials were found studying topical steroids in
      CRS patients. CONCLUSION: A high aggregate quality of evidence supports the
      effectiveness of saline irrigations in treating CRS. There is insufficient
      evidence to support a clear benefit of topical antibiotics in patients with
      chronic rhinosinusitis. Topical antifungal therapies have not been shown to be
      significantly different in efficacy than saline controls on CRS outcomes. Topical
      steroids are beneficial in the treatment of CRS with nasal polyps, but have not
      been shown to be effective in CRS without nasal polyps.

PMID- 23553556
TI  - Auxin: a master regulator in plant root development.
AB  - The demand for increased crop productivity and the predicted challenges related
      to plant survival under adverse environmental conditions have renewed the
      interest in research in root biology. Various physiological and genetic studies
      have provided ample evidence in support of the role of plant growth regulators in
      root development. The biosynthesis and transport of auxin and its signaling play
      a crucial role in controlling root growth and development. The univocal role of
      auxin in root development has established it as a master regulator. Other plant
      hormones, such as cytokinins, brassinosteroids, ethylene, abscisic acid,
      gibberellins, jasmonic acid, polyamines and strigolactones interact either
      synergistically or antagonistically with auxin to trigger cascades of events
      leading to root morphogenesis and development. In recent years, the availability
      of biological resources, development of modern tools and experimental approaches
      have led to the advancement of knowledge in root development. Research in the
      areas of hormone signal perception, understanding network of events involved in
      hormone action and the transport of plant hormones has added a new dimension to
      root biology. The present review highlights some of the important conceptual
      developments in the interplay of auxin and other plant hormones and associated
      downstream events affecting root development.

PMID- 23553559
TI  - Population differences in the relationship between height, weight, and adiposity:
      an application of Burton's model.
AB  - The study of human variation in adiposity and lean mass is important for
      understanding core processes in human evolution, and is increasingly a public
      health concern as the "obesity epidemic" expands globally. The dominant measure
      of population differences in adiposity is Body Mass Index (BMI), which suffers
      from systematic biases across populations due to variation in the relationship
      between true body fat, height and weight. Here we develop simplified corrections
      for such anthropometric-based measures of adiposity that can take into account
      this population variation. These corrections derive from a recent model proposed
      by Burton that assumes humans accrue mass in two ways-growth in height that adds
      bone and muscle, and growth in body fat and the ancillary fat-free mass (FFM)
      needed to support this additional body fat. We analyze two ethnically diverse
      datasets with dual X-ray absorptiometry-measured (DXA) fat mass, assessing the
      fit of Burton's model and deriving novel corrections based on estimated
      musculoskeletal slenderness. The resulting model provides excellent fit to fat
      mass within populations (average R2 = 0.92 for women and R2 = 0.83 for men).
      World populations differ dramatically in musculoskeletal slenderness (up to a
      difference of 4.4 kg/m2), as do men and women (differences of 3.3-4.5 kg/m2),
      leading to clear population corrections. These findings point to a conceptually
      straightforward tool for estimating true differences in adiposity across
      populations, and suggest an alternative to BMI that provides a more accurate and
      theoretically based estimate of body fat than that traditionally derived from
      height and weight measures.

PMID- 23553557
TI  - Hormonal signals involved in the regulation of cambial activity, xylogenesis and
      vessel patterning in trees.
AB  - The radial growth of plant stem is based on the development of cribro-vascular
      cambium tissues. It affects the transport efficiency of water, mineral nutrients
      and photoassimilates and, ultimately, also plant height. The rate of cambial cell
      divisions for the assembly of new xylem and phloem tissue primordia and the rate
      of differentiation of the primordia into mature tissues determine the amount of
      biomass produced and, in the case of woody species, the wood quality. These
      complex physiological processes proceed at a rate which depends on several
      factors, acting at various levels: growth regulators, resource availability and
      environmental factors. Several hormonal signals and, more recently, further
      regulatory molecules, have been shown to be involved in the induction and
      maintenance of cambium and the formation of secondary vascular tissues. The
      control of xylem cell patterning is of particular interest, because it determines
      the diameter of xylem vessels, which is central to the efficiency of water and
      nutrient transport from roots to leaves through the stem and may strongly
      influence the growth in height of the tree. Increasing scientific evidence have
      proved the role of other hormones in cambial cell activities and the study of the
      hormonal signals and their crosstalking in cambial cells may foster our
      understanding of the dynamics of xylogenesis and of the mechanism of vessel size
      control along the stem. In this article, the role of the hormonal signals
      involved in the control of cambium and xylem development in trees and their
      crosstalking are reviewed.

PMID- 23553561
TI  - Left ventricular hypertrabeculation/noncompaction in beta-thalassemia.

PMID- 23553560
TI  - Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and
      pharmacodynamic analysis.
AB  - Axitinib is a potent and selective inhibitor of vascular endothelial growth
      factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal
      cell carcinoma (RCC). Axitinib population pharmacokinetic and
      pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear
      mixed effects modeling with pooled data from 383 healthy volunteers, 181 patients
      with metastatic RCC, and 26 patients with other solid tumors in 17 trials, the
      disposition of axitinib was best described by a 2-compartment model with first
      order absorption and a lag time, with estimated mean systemic clearance (CL) of
      14.6 L/h and central volume of distribution (V(c)) of 47.3 L. Of 12 covariates
      tested, age over 60 years and Japanese ethnicity were associated with decreased
      CL, whereas V(c) increased with body weight. However, the magnitude of predicted
      changes in exposure based on these covariates does not warrant dose adjustments.
      Multivariate Cox proportional hazard regression and logistic regression analyses
      showed that higher exposure and diastolic blood pressure were independently
      associated with longer progression-free and overall survivals and higher
      probability of partial response in metastatic RCC patients. These findings
      support axitinib dose titration to increase plasma exposure in patients who
      tolerate axitinib, and also demonstrate diastolic blood pressure as a potential
      marker of efficacy.

PMID- 23553562
TI  - Sequence length determinants for self-assembly of amphipathic beta-sheet
      peptides.
AB  - Amphipathic peptides composed of alternating hydrophobic and hydrophilic amino
      acids are a privileged class of peptide, which have a high propensity to self
      assemble into beta-sheet fibrils. The Ac-(FKFE)2-NH2 peptide has been extensively
      studied and forms putative beta-sheet bilayer fibrils in which the hydrophobic
      Phe side chains are organized to a single face of each constituent sheet; upon
      bilayer formation, these hydrophobic benzyl groups are sequestered in the
      hydrophobic core of the resulting fibril. In order for the Phe side chains to be
      uniformly displayed on one face of Ac-(FKFE)2-NH2 beta-sheets, an antiparallel
      packing orientation in which one amino acid residue is unpaired must be adopted.
      Based on molecular models, we hypothesized that truncated seven amino acid
      derivatives of Ac-(FKFE)2-NH2 in which either the N-terminal Phe residue (Ac
      KFEFKFE-NH2) or the C-terminal Glu residue (Ac-FKFEFKF-NH2) is eliminated should
      readily self-assemble into beta-sheet bilayers in which all hydrogen bond and
      hydrophobic/charge interactions are satisfied. We found, however, that these
      minute changes in peptide sequence have unanticipated and dramatic effects on the
      self-assembly of each peptide. Ac-FKFEFKF-NH2 self-assembled into fibrils with
      unique morphology relative to the parent peptide, whereas the Ac-KFEFKFE-NH2
      peptide had a strongly reduced propensity to self-assemble, even failing to self
      assemble altogether under some conditions. These findings provide significant
      insight into the effect of sequence length and strand registry as well as
      hydrophobicity and charge on the self-assembly of simple amphipathic peptides to
      illuminate the possibility of tuning self-assembly processes and the resulting
      structures with minute changes to peptide sequence.

PMID- 23553564
TI  - Occupational asthma and rhinitis caused by cyanoacrylate-based eyelash extension
      glues.
AB  - BACKGROUND: Eyelash extensions are applied on top of customers' lashes using
      instant glue containing cyano acrylate, known to cause occupational rhinitis (OR)
      and occupational asthma (OA). The number of beauty professionals applying these
      extensions is increasing due to their popularity. AIMS: To report on a case of OA
      with OR and a case of OR attributable to lash extension glue and to evaluate
      respiratory exposure in lash extension work. METHODS: Two beauty professionals
      with suspected OA and/or OR underwent inhalation challenge, including both
      control challenge and work-mimicking challenges using the lash extension glue,
      each with a 24-h follow-up. Volatile organic compounds (VOCs) present were
      assessed during the lash extension glue challenge. The glues were analysed for
      their (meth)acrylate content. RESULTS: Both beauty professionals (case 1 and case
      2) applied lash extensions regularly for several hours per day as part of their
      work and had work-related rhinitis. Case 1 had a longer history of lash extension
      work and also had asthmatic symptoms. The first lash extension glue challenge was
      negative in both cases, but positive OR reactions were detected in the second
      test. Case 1 also had a late asthmatic reaction. During the lash extension glue
      challenge, VOC were present in total concentrations below the irritant threshold
      and ethylcyanoacrylate (ECA) was detected in a concentration of 0.4mg/m(3).
      Chemical analysis of the glues revealed ECA was the major component. CONCLUSIONS:
      Application of eyelash extensions using small amounts of cyanoacrylate-based
      glues can cause OA and OR.

PMID- 23553563
TI  - VEGFA SNPs and transcriptional factor binding sites associated with high altitude
      sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.
AB  - Mountain sickness (MS) occurs among humans visiting or inhabiting high altitude
      environments. We conducted genetic analyses of seven single nucleotide
      polymorphisms (SNPs) in the promoter region of VEGFA gene for lowland (Han) and
      highland (Tibetan) Chinese. The seven SNPs were evaluated in Han and Tibetan
      patients with acute (A) and chronic (C) MS. We compared 64 patients with AMS with
      64 Han unaffected with MS, as well as 48 CMS patients with 32 unaffected
      Tibetans. The SNPs studied are rs699947, rs34357231, rs79469752, rs13207351,
      rs28357093, rs1570360, and rs2010963 which are found in the promoter ranging from
      -2,578 to -634 bp from the transcriptional start site (TSS), respectively. Direct
      sequencing was used to identify individual genotypes for these SNPs. Arterial
      oxygen saturation of hemoglobin (SaO2) was found to be significantly associated
      with the rs699947, rs34357231, rs13207351, and rs1570360 SNPs in Han patients
      with AMS, while the rs2010963 SNP was found to approach significance in the AMS
      study group, but found to be significantly associated in the normal Tibetan study
      group. The Han and Tibetan control groups were found to diverge significantly for
      the rs28357093 and rs2010963 SNPs, as measured by genetic distances of 0.073 and
      0.054, respectively. All the SNPs are found in transcriptional factor binding
      sites (TFBS), and their possible role in gene regulation was evaluated with
      regard to MS. MS was found to be significantly associated with these SNPs
      compared with their Han and Tibetan control groups, indicating that these
      nucleotide substitutions result in TFBS changes which apparently have a
      physiological effect on the development of high altitude sickness.

PMID- 23553565
TI  - The efficacy of psychosocial intervention for pain in breast cancer patients and
      survivors: a systematic review and meta-analysis.
AB  - Persistent pain after breast cancer treatment is prevalent, and not all patients
      respond sufficiently to pharmacological treatment. Pain is recognized as a multi
      dimensional phenomenon, which includes psychological and social components, and
      several clinical trials have investigated the efficacy of psychosocial
      interventions on pain in cancer patients and survivors. Our aim was to
      systematically review and quantify the existing research on the effect of
      psychosocial interventions on pain in breast cancer patients and survivors. Two
      independent raters reviewed 474 abstracts for eligibility, leading to the
      identification of 26 independent and eligible studies published between 1983 and
      2012, which were assessed for their methodological quality and subjected to meta
      analytic evaluation. A total of 1786 participants were included in the analyses.
      A statistically significant and robust overall effect size was found across all
      included studies (Hedges g = 0.37, 95 % CI: 0.20-0.40; p < 0.001). However, the
      effect size was considerably smaller (0.21), when adjusted for possible
      publication bias. Furthermore, the results were heterogeneous, and when exploring
      the sources of heterogeneity, studies of higher methodological quality were found
      to yield a more conservative effect size (g = 0.21, 95 % CI: 0.02-0.41) than
      studies of poorer quality (g = 0.65, 95 % CI: 0.25-1.04). The results also
      indicated that patient educational approaches yielded a larger effect size (g =
      0.64) than relaxation-based interventions (g = 0.31, 95 % CI: -0.05-0.67) and
      supportive group therapy (g = 0.17, 95 % CI: 0.02-0.32). Taken together, while
      suggestive of psychosocial intervention as an effective tool in the management of
      pain among breast cancer patients and survivors, the results should be
      interpreted as preliminary. The methodological quality of the existing research
      varied considerably, and only few studies had selected patients on the basis of
      the presence of pain and included pain as the primary outcome.

PMID- 23553567
TI  - Noninvasive ventilation inefficacy due to technically incompatible ventilator
      settings.

PMID- 23553566
TI  - Impact of recent parity on histopathological tumor features and breast cancer
      outcome in premenopausal Japanese women.
AB  - Although previous studies have reported that onset at young age is associated
      with poor prognosis in breast cancer, the correlation between reproductive
      factors, breast cancer characteristics, and prognosis remains unclear. Five
      hundred and twenty-six premenopausal young women diagnosed with primary invasive
      breast cancer between January 2000 and December 2007 were included in this study.
      Patients were classified into four groups according to their reproductive
      history: women who gave birth within the previous 2 years (group A), women who
      gave birth between 3 and 5 years previously (group B), women who gave birth more
      than 5 years previously (group C), and nulliparous women (group N). The
      correlation between the time since last childbirth to diagnosis,
      histopathological tumor features, and breast cancer prognosis was evaluated.
      Breast cancer patients who had given birth more recently had more advanced stage
      tumors; larger sized tumors; a higher rate of axillary lymph node metastases; a
      higher histological tumor grade; and increased progesterone receptor (PgR)-,
      HER2+, and triple negative tumors than patients who had given birth less recently
      or not at all. Group A patients had significantly shorter survival times than
      patients in both groups C and N (log rank test; p < 0.001). After adjusting for
      tumor characteristics, the hazard ratio for death in group A was 2.19 compared
      with group N (p = 0.036), and the adjusted hazard ratio restricted to patients in
      group A with hormone-receptor-positive, and HER2- tumors was 3.07 (p = 0.011).
      Young breast cancer patients who had given birth more recently had tumors with
      more aggressive features and worse prognoses compared with patients who had given
      birth less recently or were nulliparous.

PMID- 23553568
TI  - Ventilation distribution measured with EIT at varying levels of pressure support
      and Neurally Adjusted Ventilatory Assist in patients with ALI.
AB  - PURPOSE: The purpose of this study was to compare the effect of varying levels of
      assist during pressure support (PSV) and Neurally Adjusted Ventilatory Assist
      (NAVA) on the aeration of the dependent and non-dependent lung regions by means
      of Electrical Impedance Tomography (EIT). METHODS: We studied ten mechanically
      ventilated patients with Acute Lung Injury (ALI). Positive-End Expiratory
      Pressure (PEEP) and PSV levels were both 10 cm H2O during the initial PSV step.
      Thereafter, we changed the inspiratory pressure to 15 and 5 cm H2O during PSV.
      The electrical activity of the diaphragm (EAdi) during pressure support ten was
      used to define the initial NAVA gain (100 %). Thereafter, we changed NAVA gain to
      150 and 50 %, respectively. After each step the assist level was switched back to
      PSV 10 cm H2O or NAVA 100 % to get a new baseline. The EIT registration was
      performed continuously. RESULTS: Tidal impedance variation significantly
      decreased during descending PSV levels within patients, whereas not during NAVA.
      The dorsal-to-ventral impedance distribution, expressed according to the center
      of gravity index, was lower during PSV compared to NAVA. Ventilation contribution
      of the dependent lung region was equally in balance with the non-dependent lung
      region during PSV 5 cm H2O, NAVA 50 and 100 %. CONCLUSION: Neurally Adjusted
      Ventilatory Assist ventilation had a beneficial effect on the ventilation of the
      dependent lung region and showed less over-assistance compared to PSV in patients
      with ALI.

PMID- 23553569
TI  - Nano-composite scaffolds for bone tissue engineering containing silver
      nanoparticles: preparation, characterization and biological properties.
AB  - In this study nano-composite scaffolds to be used as bone grafts have been
      endowed with antibacterial properties owing to the presence of silver
      nanoparticles. The alginate/hydroxyapatite composite scaffolds were prepared by
      internal gelation followed by a freeze-drying procedure to obtain a porous
      structure. The nanoparticles were prepared in presence of a lactose modified
      chitosan and this colloidal solution was adsorbed on the scaffolds by exploiting
      electrostatic interactions. The adsorption and release of the silver from the
      composite scaffold was measured by ICP-AES and spectrofluorimetry measurements.
      Micro-computed tomography analysis of the scaffolds showed a homogeneous porous
      structure with average pore sizes of 341.5 MUm and porosity of 80 %. In vitro
      biological tests (MTS and killing kinetics assays) demonstrated that silver does
      not affect the ability of the scaffolds to promote osteoblasts proliferation and
      that at the same time it exerts a strong bactericidal effect against both Gram+
      and Gram- bacterial strains. Overall, the combined results indicate that these
      biocompatible antimicrobial scaffolds possess ideal characteristics for tissue
      engineering applications. 

PMID- 23553570
TI  - Comprehensive validation of cardiovascular magnetic resonance techniques for the
      assessment of myocardial extracellular volume.
AB  - BACKGROUND: Extracellular matrix expansion is a key element of ventricular
      remodeling and a potential therapeutic target. Cardiovascular magnetic resonance
      (CMR) T1-mapping techniques are increasingly used to evaluate myocardial
      extracellular volume (ECV); however, the most widely applied methods are without
      histological validation. Our aim was to perform comprehensive validation of (1)
      dynamic-equilibrium CMR (DynEq-CMR), where ECV is quantified using hematocrit
      adjusted myocardial and blood T1 values measured before and after gadolinium
      bolus; and (2) isolated measurement of myocardial T1, used as an ECV surrogate.
      METHODS AND RESULTS: Whole-heart histological validation was performed using 96
      tissue samples, analyzed for picrosirius red collagen volume fraction, obtained
      from each of 16 segments of the explanted hearts of 6 patients undergoing heart
      transplantation who had prospectively undergone CMR before transplantation
      (median interval between CMR and transplantation, 29 days). DynEq-CMR-derived ECV
      was calculated from T1 measurements made using a modified Look-Locker inversion
      recovery sequence before and 10 and 15 minutes post contrast. In addition, ECV
      was measured 2 to 20 minutes post contrast in 30 healthy volunteers. There was a
      strong linear relationship between DynEq-CMR-derived ECV and histological
      collagen volume fraction (P<0.001; within-subject: r=0.745; P<0.001; r(2)=0.555
      and between-subject: r=0.945; P<0.01; r(2)=0.893; for ECV calculated using 15
      minute postcontrast T1). Correlation was maintained throughout the entire heart.
      Isolated postcontrast T1 measurement showed significant within-subject
      correlation with histological collagen volume fraction (r=-0.741; P<0.001;
      r(2)=0.550 for 15-minute postcontrast T1), but between-subject correlations were
      not significant. DynEq-CMR-derived ECV varied significantly according to contrast
      dose, myocardial region, and sex. CONCLUSIONS: DynEq-CMR-derived ECV shows a good
      correlation with histological collagen volume fraction throughout the whole
      heart. Isolated postcontrast T1 measurement is insufficient for ECV assessment.

PMID- 23553571
TI  - 7-T MRI of the spinal cord can detect lateral corticospinal tract abnormality in
      amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive
      neurodegenerative disorder affecting lower and upper motor neurons. Degeneration
      of the lateral corticospinal tract (CST) is a key finding in ALS cervical spinal
      cord autopsies. We hypothesized that in vivo ultra-high-field MRI of the cervical
      spinal cord can detect abnormality in the CST. METHODS: A patient with ALS
      (disease duration 23 months) and a healthy control were scanned at 7-T MRI using
      a 19-channel coil. Multi-echo T2*-weighted imaging was performed in the spinal
      cord, covering C2-C6. Cross-sectional resolution was 0.37 * 0.37 mm(2). RESULTS:
      We detected clear signal hyperintensity in both segments of the lateral CST in
      the ALS patient, which was significant when compared with the normal control
      subject (P < 10(-7)). CONCLUSION: We believe there are potential benefits of 7-T
      MRI for increased sensitivity and spatial accuracy in characterizing pathology in
      the spinal cord.

PMID- 23553573
TI  - Victims and bully-victims but not bullies are groups associated with anxiety
      symptomatology among Brazilian children and adolescents.
AB  - School bullying is frequent and is associated with a broad spectrum of
      psychiatric problems. The aims of this study were to examine the prevalence of
      bullying behaviors in a large sample of Brazilian children and adolescents and to
      investigate the association between bullying behaviors and DSM-IV anxiety
      symptomatology. This cross-sectional study involved completion of a questionnaire
      about bullying behaviors and their frequency and the Screen for Child Anxiety
      Related Emotional Disorders (SCARED) that is a self-report screening tool for
      childhood anxiety disorders by 2,355 students. A total of 22.9 % of the sample
      reported frequent involvement in bullying, as a bully (7.6 %), as a victim (5.7
      %), or as a bully-victim (9.6 %). In general, our findings showed that students
      involved in bullying behaviors, as victims or bully-victims, were more likely to
      have higher scores in SCARED total and its subscales than bullies and than
      uninvolved students. The prevalence of bullying behaviors among Brazilian youth
      is about average when compared with previous samples described in the literature.
      Victims and bully-victims, but no bullies, are groups associated with higher
      anxiety symptomatology.

PMID- 23553574
TI  - Mandatory electrocardiographic monitoring in young patients treated with
      psychoactive drugs.

PMID- 23553572
TI  - Neuroimaging in children, adolescents and young adults with psychological trauma.
AB  - Childhood psychological trauma is a strong predictor of psychopathology.
      Preclinical research points to the influence of this type of trauma on brain
      development. However, the effects of psychological trauma on the developing human
      brain are less known and a challenging question is whether the effects can be
      reversed or even prevented. The aim of this review is to give an overview of
      neuroimaging studies in traumatized juveniles and young adults up till 2012.
      Neuroimaging studies in children and adolescents with traumatic experiences were
      found to be scarce. Most studies were performed by a small number of research
      groups in the United States and examined structural abnormalities. The reduction
      in hippocampal volume reported in adults with PTSD could not be confirmed in
      juveniles. The most consistent finding in children and adolescents, who
      experienced psychological trauma are structural abnormalities of the corpus
      callosum. We could not identify any studies investigating treatment effects.
      Neuroimaging studies in traumatized children and adolescents clearly lag behind
      studies in traumatized adults as well as studies on ADHD and autism. 

PMID- 23553575
TI  - Methylphenidate and atomoxetine for treatment of nocturnal enuresis in a child
      with attention-deficit hyperactivity disorder.

PMID- 23553576
TI  - Evidence-based psychotherapy in children and adolescents: advances,
      methodological and conceptual limitations, and perspectives.

PMID- 23553577
TI  - Confidence intervals for the selected population in randomized trials that adapt
      the population enrolled.
AB  - It is a challenge to design randomized trials when it is suspected that a
      treatment may benefit only certain subsets of the target population. In such
      situations, trial designs have been proposed that modify the population enrolled
      based on an interim analysis, in a preplanned manner. For example, if there is
      early evidence during the trial that the treatment only benefits a certain subset
      of the population, enrollment may then be restricted to this subset. At the end
      of such a trial, it is desirable to draw inferences about the selected
      population. We focus on constructing confidence intervals for the average
      treatment effect in the selected population. Confidence interval methods that
      fail to account for the adaptive nature of the design may fail to have the
      desired coverage probability. We provide a new procedure for constructing
      confidence intervals having at least 95% coverage probability, uniformly over a
      large class Q of possible data generating distributions. Our method involves
      computing the minimum factor c by which a standard confidence interval must be
      expanded in order to have, asymptotically, at least 95% coverage probability,
      uniformly over Q. Computing the expansion factor c is not trivial, since it is
      not a priori clear, for a given decision rule, for which data generating
      distribution leads to the worst-case coverage probability. We give an algorithm
      that computes c, and then prove an optimality property for the resulting
      confidence interval procedure.

PMID- 23553578
TI  - In situ antioxidant and antimicrobial activities of naturally occurring caffeic
      acid, p-coumaric acid and rutin, using food systems.
AB  - BACKGROUND: Three pure compounds that naturally occur in plants were of
      particular interest to our study regarding the possibility of using them as food
      preservatives: p-coumaric acid (found in peanuts, tomatoes, carrots, garlic,
      wine, vinegar, etc.), caffeic acid (found in argan oil, oats, wheat, rice and
      olive oil) and rutin (found in asparagus, citrus fruits, berries, apple, apricot,
      asparagus, beef and beer). In the following study we investigated in situ
      antioxidant and antimicrobial activities of three pure compounds, namely caffeic
      acid, p-coumaric acid and rutin, naturally occurring in plants. RESULTS: Two food
      systems were used in order to obtain information on how these compounds react in
      actual food systems rather than microbiological media. The results indicated good
      antioxidant activity in in situ food systems. For tested phenolic compounds it
      was further shown that they successively inhibited the development of the
      isolated food contaminant Staphylococcus aureus in chicken soup. Panelist found
      that organoleptic characteristics of chicken soup and pork meat improved after
      treatment with phenolics. CONCLUSION: Our findings alone, along with the
      potential use of phenolic compounds that are widespread in nature, may imply
      their potential use as preservatives in the food industry.

PMID- 23553579
TI  - Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal
      dysplasia.
AB  - X-linked hypohidrotic ectodermal dysplasia (XLHED; ectodysplasin deficiency) has
      been classically described as affecting hair, sweat glands, and dentition. What
      may be underappreciated is the effect ectodysplasin deficiency has on glands
      surrounding the airways and eyes and the resulting chronic health issues. In this
      study, 12 male children (age range 6-13 years) and 14 male adults with XLHED (18
      58 years of age) were investigated by pulmonary function tests, measurement of
      fractional exhaled nitric oxide, and by ophthalmologic assessments. Twelve
      healthy individuals (six children, six adults) served as controls. Signs of
      airway constriction and inflammation were detected in eight children with XLHED,
      including the youngest subject, and in ten adult XLHED patients. Increased tear
      osmolarity, reduced tear film break-up time, and other ocular abnormalities were
      also present at an early age. Five of 12 XLHED subjects not reporting a history
      of asthma and 7 of the 12 patients not reporting a history of dry eye issues
      showed at least two abnormal test results in the respective organ system. The
      presence of residual sweat ducts, suggestive of partial ectodysplasin gene
      expression, correlated with milder disease in two XLHED subjects with mutations
      affecting the collagen-like domain of ectodysplasin. CONCLUSION: The high
      prevalence of asthma-like symptoms in XLHED patients as young as 6 years and a
      similar prevalence of dry eye problems indicate that screening evaluation,
      regular monitoring, and consideration of therapeutic intervention should begin in
      early childhood.

PMID- 23553580
TI  - Reply to the correspondence letter by N Kluger et al. 'Medical alert tattoos in
      minors should not be advocated'.

PMID- 23553581
TI  - Variation of Zr-L2,3 XANES in tetravalent zirconium oxides.
AB  - Zr-L2,3 XANESs of tetravalent zirconium oxides with different coordination
      numbers and local symmetries are systematically investigated by ab initio
      multiplet calculations using fully relativistic molecular spinors for model
      clusters. Experimental Zr-L2,3 XANESs are obtained for SrZrO3, m-ZrO2
      (monoclinic) and t-ZrO2 (tetragonal). The theoretical spectra are in good
      agreement with the experimental data. The multiplet effects are found to play
      essential roles in determining the peak shape. The shapes of L3- and L2-edges are
      systematically different. The intensity ratios of the doublet peaks at both L3-
      and L2-edges are found to be sensitive to the coordination number of Zr. The
      ratio can therefore be used to estimate the coordination number of Zr in such
      oxides.

PMID- 23553582
TI  - Gentamicin pharmacokinetics and dosing in neonates with hypoxic ischemic
      encephalopathy receiving hypothermia.
AB  - STUDY OBJECTIVE: To evaluate the pharmacokinetics of gentamicin in neonates with
      hypoxic ischemic encephalopathy (HIE) receiving hypothermia and to identify an
      empiric gentamicin dosing strategy in this population that optimizes achievement
      of target peak and trough concentrations. DESIGN: Population pharmacokinetic
      study using retrospective medical record data. SETTING: Tertiary neonatal
      intensive care unit. PATIENTS: A total of 29 full-term neonates diagnosed with
      HIE treated with hypothermia who received gentamicin and underwent therapeutic
      drug monitoring MEASUREMENT AND MAIN RESULTS: Patient demographics and gentamicin
      concentration data were retrospectively collected over a 2-year period. A
      population-based pharmacokinetic model was developed using nonlinear mixed
      effects modeling (NONMEM). Using the developed model, Monte Carlo simulations
      were performed to evaluate the probability of achieving target peak (> 6 mg/L)
      and trough (< 2 mg/L) gentamicin concentrations for various potential dosing
      regimens. A one-compartment model best described the available gentamicin
      concentration data. Birthweight and serum creatinine significantly influenced
      gentamicin clearance. For the typical study neonate (birthweight 3.3 kg, serum
      creatinine 0.9 mg/dl), clearance was 0.034 L/hour/kg and volume was 0.52 L/kg. At
      a 24-hour dosing interval, Monte Carlo simulations predicted target gentamicin
      peak and trough concentrations could not be reliably achieved at any dose. At a
      36-hour dosing interval, a dose of 4-5 mg/kg is predicted to achieve target
      gentamicin peak and trough concentrations in more than 90% of neonates.
      CONCLUSIONS: Gentamicin clearance is decreased in neonates with HIE treated with
      hypothermia compared with previous reports in nonasphyxiated normothermic full
      term neonates. A prolonged 36-hour dosing interval will be needed to achieve
      target gentamicin trough concentrations in this population. Further prospective
      evaluation of this dosing recommendation is needed.

PMID- 23553583
TI  - A simple mechanical device reduces subglottic injury in ventilated animals.
AB  - OBJECTIVES/HYPOTHESIS: To test whether a simple inexpensive device that
      dynamically minimizes endotracheal cuff pressure throughout the respiratory cycle
      reduces endotracheal cuff pressure-related subglottic injury. STUDY DESIGN:
      Hypoxic animal model with one control and one experimental group. METHODS: Twelve
      S. scrofa domesticus piglets (14-16 kg) were intubated with standard endotracheal
      tubes and maintained in a hypoxic state to accelerate airway injury. Animals in
      the control group (n = 6) were ventilated with a constant pressure of 20 cm H2O
      in the endotracheal tube cuff. Animals in the experimental group (n = 6) were
      ventilated using a custom-designed circuit that altered the pressure in the
      endotracheal tube cuff in synchrony with the ventilatory cycle. Larynges were
      harvested at the end of the experiment and examined histologically to determine
      the degree of airway injury induced by the endotracheal cuff. RESULTS: Animals in
      the experimental group suffered significantly less airway damage than those in
      the control group. The differences were seen primarily in the subglottis
      (aggregate damage score 6.5 vs. 12, P <0.05), where the experimental endotracheal
      tube cuff exerted the least pressure. There was no difference in damage to the
      glottic or supraglottic structures. CONCLUSIONS: A simple, reliable, and
      inexpensive means of modulating endotracheal tube cuff pressure with the
      ventilatory cycle led to a substantial decrease in airway injury in our animal
      model. Such reduction in cuff pressure may prove important for humans,
      particularly those in intensive care units who tend to have underlying conditions
      predisposing them to tracheal damage from the endotracheal tube cuff.

PMID- 23553584
TI  - Prognostic value of unrecognised myocardial infarction detected by late
      gadolinium-enhanced MRI in diabetic patients with normal global and regional left
      ventricular systolic function.
AB  - OBJECTIVES: To determine whether the detection of unrecognised myocardial
      infarction (MI) using late gadolinium-enhanced (LGE)-magnetic resonance imaging
      (MRI) can provide prognostic information in diabetic patients with normal ECG as
      well as normal global and regional left ventricular (LV) function. METHODS: From
      449 diabetic patients who had complete cine- and LGE-MRI, 321 patients with
      histories of CAD, ischaemic ECG changes and abnormal cine MRI findings (LV
      ejection fraction <50 % or presence of regional wall motion abnormality) were
      excluded. The presence and extent of LGE were determined in the remaining 128
      patients. Follow-up information was obtained for the occurrence of major adverse
      cardiovascular events (MACE) defined as cardiac death, acute MI, heart failure,
      unstable angina and significant ventricular arrhythmias in 120 patients. RESULTS:
      Of 120 patients, 18 (15 %) had LGE. During follow-up (median, 27 months), six
      patients with LGE (33.3 %) and four patients without LGE (3.9 %) experienced
      MACE, resulting in an annualised event rate of 7.7 % and 0.9 %, respectively (log
      rank P <0.001). The presence of LGE was associated with an eight-fold increased
      hazard for MACE (HR, 8.84; P = 0.001). CONCLUSIONS: LGE-MRI can detect
      unrecognised MI and may improve the risk stratification of diabetic patients with
      no CAD history, normal ECG and normal LV systolic function. KEY POINTS: * Late
      gadolinium-enhanced magnetic resonance imaging (LGE-MRI) can identify subtle
      myocardial abnormalities. * LGE-MRI can detect myocardial infarction missed by
      ECG and cine-MRI. * Unrecognised MI detected by LGE-MRI was associated with
      adverse cardiac events. * LGE-MRI helps clinicians to assess diabetic patients
      with unrecognised MI.

PMID- 23553585
TI  - Prospective trial comparing full-field digital mammography (FFDM) versus combined
      FFDM and tomosynthesis in a population-based screening programme using
      independent double reading with arbitration.
AB  - OBJECTIVES: To compare double readings when interpreting full field digital
      mammography (2D) and tomosynthesis (3D) during mammographic screening. METHODS: A
      prospective, Ethical Committee approved screening study is underway. During the
      first year 12,621 consenting women underwent both 2D and 3D imaging. Each
      examination was independently interpreted by four radiologists under four reading
      modes: Arm A-2D; Arm B-2D + CAD; Arm C-2D + 3D; Arm D-synthesised 2D + 3D.
      Examinations with a positive score by at least one reader were discussed at an
      arbitration meeting before a final management decision. Paired double reading of
      2D (Arm A + B) and 2D + 3D (Arm C + D) were analysed. Performance measures were
      compared using generalised linear mixed models, accounting for inter-reader
      performance heterogeneity (P < 0.05). RESULTS: Pre-arbitration false-positive
      scores were 10.3 % (1,286/12,501) and 8.5 % (1,057/12,501) for 2D and 2D + 3D,
      respectively (P < 0.001). Recall rates were 2.9 % (365/12,621) and 3.7 %
      (463/12,621), respectively (P = 0.005). Cancer detection was 7.1 (90/12,621) and
      9.4 (119/12,621) per 1,000 examinations, respectively (30 % increase, P < 0.001);
      positive predictive values (detected cancer patients per 100 recalls) were 24.7 %
      and 25.5 %, respectively (P = 0.97). Using 2D + 3D, double-reading radiologists
      detected 27 additional invasive cancers (P < 0.001). CONCLUSION: Double reading
      of 2D + 3D significantly improves the cancer detection rate in mammography
      screening. KEY POINTS: * Tomosynthesis-based screening was successfully
      implemented in a large prospective screening trial. * Double reading of
      tomosynthesis-based examinations significantly reduced false-positive
      interpretations. * Double reading of tomosynthesis significantly increased the
      detection of invasive cancers.

PMID- 23553586
TI  - Perfusion CT allows prediction of therapy response in non-small cell lung cancer
      treated with conventional and anti-angiogenic chemotherapy.
AB  - OBJECTIVES: To determine whether CT can depict early perfusion changes in lung
      cancer treated by anti-angiogenic drugs, allowing prediction of response.
      METHODS: Patients with non-small cell lung cancer, treated by conventional
      chemotherapy with (Group 1; n = 17) or without (Group 2; n = 23) anti-vascular
      endothelial growth factor (anti-VEGF) drug (bevacizumab) underwent CT perfusion
      before (TIME 0) and after 1 (TIME 1), 3 (TIME 2) and 6 (TIME 3) cycles of
      chemotherapy. The CT parameters evaluated included: (1) total tumour vascular
      volume (TVV) and total tumour extravascular flow (TEF); (2) RECIST (Response
      Evaluation Criteria in Solid Tumours) measurements. Tumour response was also
      assessed on the basis of the clinicians' overall evaluation. RESULTS: In Group 1,
      significant reduction in perfusion was identified between baseline and: (1) TIME
      1 (TVV, P = 0.0395; TEF, P = 0.015); (2) TIME 2 (TVV, P = 0.0043; TEF, P <
      0.0001); (3) TIME 3 (TVV, P = 0.0034; TEF, P = 0.0005) without any significant
      change in Group 2. In Group 1: (1) the reduction in TVV at TIME 1 was
      significantly higher in responders versus non-responders at TIME 2 according to
      RECIST (P = 0.0128) and overall clinicians' evaluation (P = 0.0079); (2) all
      responders at TIME 2 had a concurrent decrease in TVV and TEF at TIME 1.
      CONCLUSION: Perfusion CT demonstrates early changes in lung cancer vascularity
      under anti-angiogenic chemotherapy that may help predict therapeutic response.
      KEY POINTS: * Perfusion CT has the potential of providing in vivo information
      about tumour vasculature. * CT depicts early and specific perfusion changes in
      NSCLC under anti-angiogenic drugs. * Specific therapeutic effects of anti
      angiogenic drugs can be detected before tumour shrinkage. * Early perfusion
      changes can help predict therapeutic response to anti-angiogenic treatment. *
      Perfusion CT could be a non-invasive tool to monitor anti-angiogenic treatment.

PMID- 23553587
TI  - Quantification and characterisation of coronary artery plaque volume and adverse
      plaque features by coronary computed tomographic angiography: a direct comparison
      to intravascular ultrasound.
AB  - OBJECTIVE: We evaluated the performance of manual measures of coronary plaque
      volumes and atherosclerotic plaque features from coronary CT angiography (CTA),
      using intravascular ultrasound (IVUS) as the reference. METHODS: Thirty
      individual coronary plaques with suitable fiduciary markers were identified.
      Plaque volumes on coronary CTA were manually quantified by two observers and
      compared to IVUS plaque volumes as interpreted by an independent laboratory. The
      presence of adverse plaque characteristics-low attenuation plaque (LAP), positive
      remodelling (PR) and spotty calcification (SC)-on coronary CTA was evaluated and
      compared to IVUS. RESULTS: High correlation in plaque volumes was detected
      between observers (r = 0.94, P < 0.0001; 95 % limits of agreement <48.7 mm(3),
      bias 6.6 mm(3)). Excellent correlation (r = 0.95, P < 0.0001) was noted in plaque
      volume between independent observers and IVUS (95 % limits of agreement <40.6
      mm(3), bias -4.4 mm(3)) and did not differ from IVUS (105.0 +/- 56.7 vs. 109.4 +/
      60.7 mm(3), P = 0.2). The frequency of LAP (10 % vs. 17 %), PR (7 % vs. 10 %)
      and SC (27 % vs. 33 %) was similar between coronary CTA and IVUS (all P = NS).
      CONCLUSIONS: Plaque volume on coronary CTA determined by manual methods
      demonstrates high correlation and modest agreement to IVUS. Further, coronary CTA
      demonstrates high accuracy for the identification of adverse plaque
      characteristics, including LAP, PR and SC. KEY POINTS: * Coronary CT angiography
      is a non-invasive test that enables coronary plaque assessment * Plaque
      quantification by coronary CT angiography correlates well with intravascular
      ultrasound findings * Coronary CT angiography can identify adverse plaque
      characteristics.

PMID- 23553588
TI  - CEM43 degrees C thermal dose thresholds: a potential guide for magnetic resonance
      radiofrequency exposure levels?
AB  - OBJECTIVE: To define thresholds of safe local temperature increases for MR
      equipment that exposes patients to radiofrequency fields of high intensities for
      long duration. These MR systems induce heterogeneous energy absorption patterns
      inside the body and can create localised hotspots with a risk of overheating.
      METHODS: The MRI + EUREKA research consortium organised a "Thermal Workshop on RF
      Hotspots". The available literature on thresholds for thermal damage and the
      validity of the thermal dose (TD) model were discussed. RESULTS/CONCLUSIONS: The
      following global TD threshold guidelines for safe use of MR are proposed: 1. All
      persons: maximum local temperature of any tissue limited to 39  degrees C 2.
      Persons with compromised thermoregulation AND (a) Uncontrolled conditions:
      maximum local temperature limited to 39  degrees C (b) Controlled conditions: TD
      < 2 CEM43 degrees C 3. Persons with uncompromised thermoregulation AND (a)
      Uncontrolled conditions: TD < 2 CEM43 degrees C (b) Controlled conditions: TD < 9
      CEM43 degrees C The following definitions are applied: Controlled conditions A
      medical doctor or a dedicated trained person can respond instantly to heat
      induced physiological stress Compromised thermoregulation All persons with
      impaired systemic or reduced local thermoregulation KEY POINTS: * Standard MRI
      can cause local heating by radiofrequency absorption. * Monitoring thermal dose
      (in units of CEM43 degrees C) can control risk during MRI. * 9 CEM43 degrees C
      seems an acceptable thermal dose threshold for most patients. * For skin, muscle,
      fat and bone,16 CEM43 degrees C is likely acceptable.

PMID- 23553589
TI  - Shear wave elastography of tumour growth in a human breast cancer model with
      pathological correlation.
AB  - OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using
      shear wave elastography (SWE) during tumour growth and to correlate the results
      with pathology. METHODS: Local ethics committee for animal research approval was
      obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24
      athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours,
      every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven
      tumours were measured both in vivo and ex vivo. Tumours of different sizes were
      removed for pathological analysis on which the percentages of viable cellular
      tissue, fibrosis and necrosis were measured. RESULTS: A total of 63 SWE
      measurements were performed. Stiffness increased during tumour growth with an
      excellent correlation with size (r = 0.94, P < 0.0001). No differences were found
      between the values of stiffness in vivo and ex vivo (P = 0.81). There was a
      significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a
      negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant
      correlation with cellular tissue (r = 0.40, p = 0.1). CONCLUSION: Fibrosis plays
      an important role in stiffness as measured by SWE, whereas necrosis is correlated
      with softness. KEY POINTS: * In a breast cancer model, ultrasound tumour
      stiffness is correlated with size. * Stiffness changes with tumour growth are
      correlated with pathological changes. * Stiffness is very well correlated with
      proportion of tumour fibrosis. * Stiffness is inversely correlated with
      proportion of tumour necrosis. * Tumour stiffness measurements are similar in
      vivo and ex vivo.

PMID- 23553590
TI  - PCR detection of ansA from marine bacteria and its sequence characteristics from
      Bacillus tequilensis NIOS4.
AB  - As many as 71 marine bacterial DNA extracts were PCR screened for L-asparaginase
      (ansA), a key gene in anti-cancer molecular-searches. Over 62% (44) of them were
      positive for ansA gene. The positive cultures were from genera Bacillus and
      Staphylococcus. The ansA gene cloned from isolate NIOS4 belonging to recently
      described Bacillus tequilensis is 1099 bp in length with a 990 bp ORF coding for
      329 amino acids. BLASTx analysis revealed this sequence to be 98% similar to
      earlier reported ansA sequence from B. subtilis (Accession no. NP390239.1). By
      comparing its deduced amino acid sequence with other bacterial asparaginase
      sequences six substitutions at positions 305(Thr), 313(Lys), 314(Leu), 315(Asp),
      318(Arg), and 320(Gln) are observed. Key residues like Thr(12), Thr(85), Asp(86),
      Lys(156), and Phe(165) taking part in active-site formation and imparting
      catalytic properties are conserved. The phylogenetic tree based of the ansA amino
      acid sequences revealed close relatedness of the NIOS4 ansA sequence with B.
      subtilis (Accession no. NP 390239.1). It's very close genetic resemblance to B.
      subtilis and conservation of certain key amino acid residues suggest it as a
      prospective candidate for evaluation and, production of L-asparaginases. 

PMID- 23553592
TI  - Alcohol consumption and risk of lymphoid and myeloid neoplasms: results of the
      Netherlands cohort study.
AB  - Results from epidemiological studies suggest that alcohol drinkers have a
      decreased risk of lymphoid neoplasms, whereas results for myeloid neoplasms are
      inconsistent. However, most of these studies have used retrospective data. We
      examined prospectively whether alcohol consumption decreases the risk of both
      lymphoid and myeloid neoplasms, including most common subtypes. Moreover, we
      investigated whether this decreased risk is due to ethanol or other contents of
      specific alcoholic beverages (i.e., beer, wine and liquor). The Netherlands
      cohort study consisted of 120,852 individuals who completed a baseline
      questionnaire in 1986. After 17.3 years of follow-up, 1,375 cases of lymphoid and
      245 cases of myeloid neoplasms with complete exposure information were available
      for analysis. Compared with abstinence, we observed for plasma cell neoplasms
      hazard rate ratios (HR) of 1.66 (95% confidence interval (CI), 1.21-2.29), 1.63
      (95% CI, 1.17-2.27), 1.11 (95% CI, 0.75-1.64) and 0.85 (95% CI, 0.51-1.42) with
      daily ethanol consumption of 0.1-<5, 5-<15, 15-<30 and >=30 g, respectively. A
      similar pattern was observed for chronic lymphocytic leukemia/small lymphocytic
      lymphoma. No associations were observed for other subtypes and for myeloid
      neoplasms. When results were analyzed by beverage type, no clear associations
      were observed. In conclusion, our study did not show an inverse association
      between alcohol consumption and lymphoid neoplasms. Also, no inverse association
      was observed with myeloid neoplasms. If any association between alcohol
      consumption and lymphoid neoplasms exists, our study suggests an increased risk
      rather than a decreased risk. 

PMID- 23553591
TI  - Hepatic macrophages but not dendritic cells contribute to liver fibrosis by
      promoting the survival of activated hepatic stellate cells in mice.
AB  - Although it is well established that hepatic macrophages play a crucial role in
      the development of liver fibrosis, the underlying mechanisms remain largely
      elusive. Moreover, it is not known whether other mononuclear phagocytes such as
      dendritic cells (DCs) contribute to hepatic stellate cell (HSC) activation and
      liver fibrosis. We show for the first time that hepatic macrophages enhance
      myofibroblast survival in a nuclear factor kappa B (NF-kappaB)-dependent manner
      and thereby promote liver fibrosis. Microarray and pathway analysis revealed no
      induction of HSC activation pathways by hepatic macrophages but a profound
      activation of the NF-kappaB pathway in HSCs. Conversely, depletion of mononuclear
      phagocytes during fibrogenesis in vivo resulted in suppressed NF-kappaB
      activation in HSCs. Macrophage-induced activation of NF-kappaB in HSCs in vitro
      and in vivo was mediated by interleukin (IL)-1 and tumor necrosis factor (TNF).
      Notably, IL-1 and TNF did not promote HSC activation but promoted survival of
      activated HSCs in vitro and in vivo and thereby increased liver fibrosis, as
      demonstrated by neutralization in coculture experiments and genetic ablation of
      IL-1 and TNF receptor in vivo. Coculture and in vivo ablation experiments
      revealed only a minor contribution to NF-kappaB activation in HSCs by DCs, and no
      contribution of DCs to liver fibrosis development, respectively. CONCLUSION:
      Promotion of NF-kappaB-dependent myofibroblast survival by macrophages but not
      DCs provides a novel link between inflammation and fibrosis.

PMID- 23553593
TI  - Combined effect of glycation and sodium carbonate-bicarbonate buffer
      concentration on IgG binding, IgE binding and conformation of ovalbumin.
AB  - BACKGROUND: Ovalbumin (OVA) is a major allergen in hen egg. During thermal
      processing, reducing sugars contained in the hen egg white might easily undergo
      glycation with OVA, but few studies have been conducted on its corresponding
      immunoreactivity changes. The aim of the present study was to assess changes of
      the antigenicity, potential allergenicity and conformation of OVA after glycation
      in a wet-thermal processing system under different concentrations of sodium
      carbonate-bicarbonate buffer. RESULTS: IgE binding of the glycated OVA was
      increased after glycation, and the higher the sodium carbonate-bicarbonate buffer
      concentration, the higher the IgE binding capacity. The increase in IgE binding
      of OVA corresponded well with the disruption of the disulfide bond, which exposed
      the epitopes initially buried. Antigenicity of the glycated OVA was increased,
      and the amount of the increase varied among samples treated under different
      buffer concentrations. CONCLUSION: Glycation increased the allergenic potential
      for OVA, with the amount of increase varying with different sodium carbonate
      bicarbonate buffer concentrations.

PMID- 23553595
TI  - Aerosol particle size does not predict pharmacokinetic determined lung dose in
      children.
AB  - In vitro measures of aerosol particles size, such as the fine particle mass, play
      a pivotal role for approval of inhaled anti-asthmatic drugs. However, the
      validity as a measure of dose to the lungs in children lacks evidence. In this
      study we investigated for the first time the association between an in vivo
      estimate of lung dose of inhaled drug in children and the corresponding particle
      size segments assessed ex vivo. Lung dose of fluticasone propionate after
      inhalation from a dry powder inhaler (Diskus(r)) was studied in 23 children aged
      4-7 and 12-15 years with mild asthma. Six-hour pharmacokinetics was assessed
      after single inhalation. The corresponding emitted mass of drug in segments of
      aerosol particle size was assessed ex vivo by replicating the inhalation flows
      recorded by transducers built into the Diskus(r) inhaler and re-playing them in a
      breathing simulator. There was no correlation between any inhaled particle size
      segment and lung dose assessed by pharmacokinetics and adjusted for age and body
      size. Measures of particles size segments were not related to lung dose in
      children. Until further evidence is provided it may be warranted to emphasize
      pharmacokinetic or pharmacodynamic assessments of drug delivery to the lung.

PMID- 23553594
TI  - Clinical outcomes of tigecycline alone or in combination with other antimicrobial
      agents for the treatment of patients with healthcare-associated multidrug
      resistant Acinetobacter baumannii infections.
AB  - Tigecycline (TG) has been shown to be active in vitro against Acinetobacter
      baumannii, although data on the clinical efficacy of TG alone or in combination
      for the treatment of infections due to multidrug-resistant A. baumannii (MDRAB)
      remain limited. The purpose of this study was to investigate the clinical
      outcomes of patients with healthcare-associated infections (HAIs) caused by MDRAB
      who were treated with imipenem/cilastatin and sulbactam, and TG alone or in
      combination with other antibiotics. A total of 386 patients with HAIs caused by
      MDRAB were retrospectively analyzed and grouped into TG and non-TG groups,
      depending on whether they received TG treatment. Of the 266 patients in the TG
      group, 108 were treated with TG alone and 158 were treated with TG in combination
      with ceftazidime, ceftriaxone, piperacillin/tazobactam, or a carbapenem. All 120
      patients in the non-TG group were treated with imipenem/cilastatin and sulbactam.
      The primary outcome measure was 30-day mortality after TG treatment and the
      secondary outcome was clinical outcome. There were no significant differences in
      survival rates between the two groups. However, the rate of unfavorable outcome
      was significantly lower (p < 0.05) among patients in the TG group than among
      patients in the non-TG group. The most significant predictor of unfavorable
      outcome was sepsis, whereas TG treatment and microbial eradication were the most
      significant predictors of favorable outcomes. Our study represents the largest
      study of patients with MDRAB infection treated with TG and expands our
      understanding of the role of TG therapy alone or in combination with other agents
      for the treatment of HAI caused by MDRAB.

PMID- 23553597
TI  - Adjunctive tenotomy during middle ear surgery.

PMID- 23553596
TI  - Deferasirox demonstrates a dose-dependent reduction in liver iron concentration
      and consistent efficacy across subgroups of non-transfusion-dependent thalassemia
      patients.
AB  - The 1-year THALASSA study enrolled 166 patients with various non-transfusion
      dependent thalassemia (NTDT) syndromes, degrees of iron burden and patient
      characteristics, and demonstrated the overall efficacy and safety of deferasirox
      in reducing liver iron concentration (LIC) in these patients. Here, reduction in
      LIC with deferasirox 5 and 10 mg/kg/day starting dose groups is shown to be
      consistent across the following patient subgroups-baseline LIC/serum ferritin,
      age, gender, race, splenectomy (yes/no), and underlying NTDT syndrome (beta
      thalassemia intermedia, HbE/beta-thalassemia or alpha-thalassemia). These
      analyses also evaluated deferasirox dosing strategies for patients with NTDT.
      Greater reductions in LIC were achieved in patients dose-escalated at Week 24
      from deferasirox 10 mg/kg/day starting dose to 20 mg/kg/day. Patients who
      received an average actual dose of deferasirox >12.5-<=17.5 mg/kg/day achieved a
      greater LIC decrease compared with the >=7.5-<=12.5 mg/kg/day and >0-<7.5
      mg/kg/day subgroups, demonstrating a dose-response efficacy. LIC reduction across
      patient subgroups was generally consistent with the primary efficacy analysis
      with a similar safety profile.

PMID- 23553598
TI  - Identification of tissue-preferential expression patterns of rice miRNAs.
AB  - It is imperative to understand the mechanisms of growth and development in higher
      plants for improving plant adaptation during different developmental stages.
      Plant microRNAs (miRs) play crucial regulatory roles in various developmental
      processes. As many as 15 miR families having multiple members are known to
      regulate plant development, yet the spatio-temporal expression patterns of
      individual members are not fully characterized. It is likely that different
      members of miR families can make specific contributions to the spatio-temporal
      control of targets. To understand the functional complexity of miRs and the
      amount of degeneracy existing in miR-mediated regulation of differentiated but
      developing tissues, we have identified the Osa-miR-sequences that are expressed
      in specific tissues. We adopted the approach of comparative miR profiling using
      next-generation sequencing technology followed by experimental validation. It was
      observed that 59 Osa-miR-sequences show tissue-preferential expression in local
      basmati rice variety; while 126 miRs belonging to 81 families are differentially
      regulated in these tissues. The 21 nt miRs were predominant in all tissues, but
      the 24 nt miRs were the most abundantly expressed. This indicates that target
      cleavage and chromatin state regulation are involved in organ development. This
      study also identified the expression patterns of individual members of Osa-miR
      families that were common and divergent between the indica and japonica rice
      varieties. The expression patterns of the predicted targets were also analyzed.
      The possible implications of the miR distribution patterns with respect to the
      regulation of their respective targets are discussed.

PMID- 23553599
TI  - A multimodal evaluation of microstructural white matter damage in spinocerebellar
      ataxia type 3.
AB  - Although white matter damage may play a major role in the pathogenesis of
      spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon
      macrostructural analyses. In this setting we designed a study to investigate
      white matter integrity. We evaluated 38 genetically-confirmed SCA3 patients (mean
      age, 52.76 +/- 12.70 years; 21 males) with clinical scales and brain magnetic
      resonance imaging (MRI) and 38 healthy subjects as a control group (mean age,
      48.86 +/- 12.07 years, 20 male). All individuals underwent the same protocol for
      high-resolution T1 and T2 images and diffusion tensor imaging acquisition (32
      directions) in a 3-T scanner. We used Tract-Based Spatial Statistics (FSL 4.1.4)
      to analyze diffusion data and SPM8/DARTEL for voxel-based morphometry of
      infratentorial structures. T2-relaxometry of cerebellum was performed with in
      house-developed software Aftervoxel and Interactive Volume Segmentation (IVS).
      Patients' mean age at onset was 40.02 +/- 11.48 years and mean duration of
      disease was 9.3 +/- 2.7 years. Mean International Cooperative Ataxia Rating Scale
      (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 +/
      4.01 and 14.65 +/- 7.33, respectively. Voxel-based morphometry demonstrated a
      volumetric reduction of gray and white matter in cerebellum and brainstem (P
      <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and
      brainstem. There were also areas of increased radial diffusivity (P <.05) in the
      cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition,
      we found decreased T2-relaxation values in the white matter of the right
      cerebellar hemisphere. Microstructural white matter dysfunction, not previously
      reported, occurs in the cerebellum and brainstem of SCA3 patients.

PMID- 23553600
TI  - Myositis with antimitochondrial antibodies diagnosed by rectus abdominis muscle
      biopsy.
AB  - INTRODUCTION: Antimitochondrial antibodies are autoantibodies detected in 90% of
      primary biliary cirrhosis (PBC) patients. Some PBC cases are complicated by
      myositis, which is difficult to confirm due to minimal histological evidence of
      inflammation in limb muscles. METHODS: Our aim was to determine the extent of
      inflammatory changes in a truncal muscle biopsy specimen from a PBC patient.
      RESULTS: A 48-year-old woman with a 5-year history of atrial fibrillation and
      chronic heart failure was evaluated for elevated serum creatine kinase level.
      Antimitochondrial M2 antibodies were detected, and PBC was diagnosed. A biceps
      brachii biopsy specimen showed mild, non-specific myogenic changes; a second
      biopsy was performed on the rectus abdominis muscle, which showed typical
      inflammatory changes. Myositis with antimitochondrial M2 antibodies was
      confirmed. CONCLUSIONS: In myositis patients with antimitochondrial M2
      antibodies, muscles of the extremities are involved to a lesser extent.
      Radiological and histological examination focusing on truncal muscles, including
      a biopsy, is important.

PMID- 23553601
TI  - Role of interleukin-1 inhibitors in the management of gout.
AB  - Interleukin-1 (IL-1) inhibitors potentially have a role as antiinflammatory
      agents in refractory gout or for patients who are unable to tolerate conventional
      therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or
      glucocorticoids, for acute attacks. Additionally, IL-1 inhibitors may also help
      patients with polyarticular and tophaceous gout by making them less vulnerable to
      breakthrough attacks during initiation of chronic urate-lowering treatment, the
      mainstay of gout therapy. Because evidence highlights the role of proinflammatory
      cytokine IL-1 in the inflammation process during an acute gouty attack, IL-1
      inhibitors are used to modulate the pathogenesis of a variety of autoinflammatory
      diseases, providing support for its potential role in the inflammatory process of
      gout. After NSAIDs, colchicine, and steroids, IL-1 inhibitors are beneficial as
      fourth-line therapy for acute gout attacks due to their high cost and limited
      clinical experience. The IL-1 inhibitors used in gout are anakinra, canakinumab,
      and rilonacept. Based on published evidence, anakinra has limited support in the
      form of anecdotal case reports to justify its use for treating gout.
      Canakinumab's toxic profile in clinical trials precludes its use in treating
      patients for gout, and rilonacept shows promise with a few well-designed studies
      to support its use in gout patients initiating urate-lowering treatment. When
      combined with current traditional therapies, these newer agents present
      clinicians and patients with more potential treatment options in the difficult-to
      treat gout population. 

PMID- 23553602
TI  - Peptide design for antimicrobial and immunomodulatory applications.
AB  - The increasing threat of antibiotic resistance in pathogenic bacteria and the
      dwindling supply of antibiotics available to combat these infections poses a
      significant threat to human health throughout the world. Antimicrobial peptides
      (AMPs) have long been touted as the next generation of antibiotics capable of
      filling the anti-infective void. Unfortunately, peptide-based antibiotics have
      yet to realize their potential as novel pharmaceuticals, in spite of the immense
      number of known AMP sequences and our improved understanding of their
      antibacterial mechanism of action. Recently, the immunomodulatory properties of
      certain AMPs have become appreciated. The ability of small synthetic peptides to
      protect against infection in vivo has demonstrated that modulation of the innate
      immune response is an effective strategy to further develop peptides as novel
      anti-infectives. This review focuses on the screening methods that have been used
      to assess novel peptide sequences for their antibacterial and immunomodulatory
      properties. It will also examine how we have progressed in our ability to
      identify and optimize peptides with desired biological characteristics and
      enhanced therapeutic potential. In addition, the current challenges to the
      development of peptides as anti-infectives are examined and the strategies being
      used to overcome these issues are discussed.

PMID- 23553605
TI  - Sample size determination and re-estimation for matched pair designs with
      multiple binary endpoints.
AB  - Motivated by a recent symptom management trial to simultaneously assess multiple
      binary endpoints for cancer chemotherapy, we extend the univariate McNemar test
      to multivariate cases for doubly blinded clinical trials with matched pairs. We
      propose a general method to test noninferiority or equivalence. The method
      employs the intersection-union principle on the marginal score statistics to
      obtain an asymptotic alpha-level test. Power formula and sample size calculation
      are provided by a simple numerical method that accounts for the correlation
      structure among the endpoints. We further consider sample size re-estimation
      through internal pilot study. To avoid the need of unblinding for doubly blinded
      trials, we also propose a blinded approach for nuisance parameter estimation. The
      effectiveness of the proposed methods is demonstrated by simulation studies.
      Application to the cancer chemotherapy trial is illustrated.

PMID- 23553604
TI  - An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell
      transmission.
AB  - Severe liver disease caused by chronic hepatitis C virus is the major indication
      for liver transplantation. Despite recent advances in antiviral therapy, drug
      toxicity and unwanted side effects render effective treatment in liver
      transplanted patients a challenging task. Virus-specific therapeutic antibodies
      are generally safe and well-tolerated, but their potential in preventing and
      treating hepatitis C virus (HCV) infection has not yet been realized due to a
      variety of issues, not least high production costs and virus variability. Heavy
      chain antibodies or nanobodies, produced by camelids, represent an exciting
      antiviral approach; they can target novel highly conserved epitopes that are
      inaccessible to normal antibodies, and they are also easy to manipulate and
      produce. We isolated four distinct nanobodies from a phage-display library
      generated from an alpaca immunized with HCV E2 glycoprotein. One of them,
      nanobody D03, recognized a novel epitope overlapping with the epitopes of several
      broadly neutralizing human monoclonal antibodies. Its crystal structure revealed
      a long complementarity determining region (CD3) folding over part of the
      framework that, in conventional antibodies, forms the interface between heavy and
      light chain. D03 neutralized a panel of retroviral particles pseudotyped with HCV
      glycoproteins from six genotypes and authentic cell culture-derived particles by
      interfering with the E2-CD81 interaction. In contrast to some of the most broadly
      neutralizing human anti-E2 monoclonal antibodies, D03 efficiently inhibited HCV
      cell-to-cell transmission. CONCLUSION: This is the first description of a potent
      and broadly neutralizing HCV-specific nanobody representing a significant advance
      that will lead to future development of novel entry inhibitors for the treatment
      and prevention of HCV infection and help our understanding of HCV cell-to-cell
      transmission.

PMID- 23553603
TI  - Nerve injury induces glial cell line-derived neurotrophic factor (GDNF)
      expression in Schwann cells through purinergic signaling and the PKC-PKD pathway.
AB  - Upon peripheral nerve injury, specific molecular events, including increases in
      the expression of selected neurotrophic factors, are initiated to prepare the
      tissue for regeneration. However, the mechanisms underlying these events and the
      nature of the cells involved are poorly understood. We used the injury-induced
      upregulation of glial cell-derived neurotrophic factor (GDNF) expression as a
      tool to gain insights into these processes. We found that both myelinating and
      nonmyelinating Schwann cells are responsible for the dramatic increase in GDNF
      expression after injury. We also demonstrate that the GDNF upregulation is
      mediated by a signaling cascade involving activation of Schwann cell purinergic
      receptors, followed by protein kinase C signaling which activates protein kinase
      D (PKD), which leads to increased GDNF transcription. Given the potent effects of
      GDNF on survival and repair of injured peripheral neurons, we propose that
      targeting these pathways may yield therapeutic tools to treat peripheral nerve
      injury and neuropathies.

PMID- 23553606
TI  - Cochlear schwannoma removed through the external auditory canal by a transcanal
      exclusive endoscopic technique.
AB  - Surgical approaches to the inner ear and internal auditory canal (IAC) are widely
      known and extensively recorded. The most popular can be classified as
      retrosigmoid, transmastoid-translabyrinthine, and middle cranial fossa
      approaches. For the first time, an exclusive endoscopic approach to the IAC is
      described here, used to remove a cochlear schwannoma involving both the IAC and
      labyrinth. The operation provided a direct transcochlear intradural approach from
      lateral to medial and from external to internal auditory canal, without any
      external incision. The pathology was totally removed, and the postoperative
      outcome of the facial nerve was grade II (House-Brackmann grading system) at 3
      month follow-up.

PMID- 23553607
TI  - Retraction note: Oleandrin-mediated expression of Fas potentiates apoptosis in
      tumor cells.

PMID- 23553609
TI  - The relationships among jaw-muscle fiber architecture, jaw morphology, and
      feeding behavior in extant apes and modern humans.
AB  - The jaw-closing muscles are responsible for generating many of the forces and
      movements associated with feeding. Muscle physiologic cross-sectional area (PCSA)
      and fiber length are two architectural parameters that heavily influence muscle
      function. While there have been numerous comparative studies of hominoid and
      hominin craniodental and mandibular morphology, little is known about hominoid
      jaw-muscle fiber architecture. We present novel data on masseter and temporalis
      internal muscle architecture for small- and large-bodied hominoids. Hominoid
      scaling patterns are evaluated and compared with representative New- (Cebus) and
      Old-World (Macaca) monkeys. Variation in hominoid jaw-muscle fiber architecture
      is related to both absolute size and allometry. PCSAs scale close to isometry
      relative to jaw length in anthropoids, but likely with positive allometry in
      hominoids. Thus, large-bodied apes may be capable of generating both absolutely
      and relatively greater muscle forces compared with smaller-bodied apes and
      monkeys. Compared with extant apes, modern humans exhibit a reduction in masseter
      PCSA relative to condyle-M1 length but retain relatively long fibers, suggesting
      humans may have sacrificed relative masseter muscle force during chewing without
      appreciably altering muscle excursion/contraction velocity. Lastly, craniometric
      estimates of PCSAs underestimate hominoid masseter and temporalis PCSAs by more
      than 50% in gorillas, and overestimate masseter PCSA by as much as 30% in humans.
      These findings underscore the difficulty of accurately estimating jaw-muscle
      fiber architecture from craniometric measures and suggest models of fossil
      hominin and hominoid bite forces will be improved by incorporating architectural
      data in estimating jaw-muscle forces.

PMID- 23553608
TI  - Induction of STEAP4 correlates with 1,25-dihydroxyvitamin D3 stimulation of
      adipogenesis in mesenchymal progenitor cells derived from human adipose tissue.
AB  - The vitamin D receptor (VDR) is expressed in human adipocytes and is transiently
      induced during early adipogenesis in mesenchymal progenitor cell models. VDR null
      mice exhibit enhanced energy expenditure and reduced adiposity even when fed high
      fat diets. Adipocyte-specific transgenic-expression of human VDR in mice enhances
      adipose tissue mass, indicating that VDR activation in adipocytes enhances lipid
      storage in vivo. In these studies, we conducted genomic profiling and
      differentiation assays in primary cultures of human adipose-derived mesenchymal
      progenitor cells to define the role of the VDR and its ligand 1,25
      dihydroxyvitamin D3 (1,25D) in adipogenesis. In the presence of adipogenic media,
      1,25D promoted lipid accumulation and enhanced the expression of FABP4, FASN, and
      PPARgamma. Mesenchymal cells derived from 6-month old VDR null mice exhibited
      impaired adipogenesis ex vivo but differentiation was restored by stable
      expression of human VDR. STEAP4, a gene that encodes a metalloreductase linked to
      obesity, insulin sensitivity, metabolic homeostasis and inflammation, was highly
      induced in human adipose cells differentiated in the presence of 1,25D but was
      minimally affected by 1,25D in undifferentiated precursors. These studies provide
      a molecular basis for recent epidemiological associations between vitamin D
      status, body weight and insulin resistance which may have relevance for
      prevention or treatment of metabolic syndrome and obesity.

PMID- 23553610
TI  - Anelasticity-induced increase of the Al-centered local symmetry in the metallic
      glass La50Ni15Al35.
AB  - The mechanism of anelastic deformation of metallic glasses is a fundamental issue
      of materials physics. A critical step toward atomic level understanding is the
      identification of measurable atomic level structural parameters that respond to
      anelastic deformation. We demonstrate that the electric-field-gradient tensor
      measured by means of (27)Al nuclear magnetic resonance in glassy La50Ni15Al35 is
      such a parameter and it reveals that anelasticity induces atomic processes that
      lead to increases of local site symmetry at Al sites. Such atomic processes could
      play an important role in the reversible slow beta process.

PMID- 23553611
TI  - Accuracy of self-reported tobacco use in newly diagnosed cancer patients.
AB  - PURPOSE: Accurate identification of tobacco use is critical to implement evidence
      based cessation treatments in cancer patients. The purpose of this study is to
      evaluate the accuracy of self-reported tobacco use in newly diagnosed cancer
      patients. METHODS: Tobacco use questionnaires and blood samples were collected
      from 233 newly diagnosed cancer patients (77 lung, 77 breast, and 79 prostate
      cancer). Blood was analyzed for cotinine levels using a commercially available
      enzyme-linked immunosorbent assay. Patients with cotinine measurements exceeding
      10 ng/mL were categorized as current smokers. Smoking status based upon cotinine
      levels was contrasted with self-report in current smokers, recent quitters (1 or
      less year since quit), non-recent quitters (>1 year since quit), and never
      smokers. Multivariate analyses were used to identify potential predictors of
      discordance between self-reported and biochemically confirmed smoking. RESULTS:
      Cotinine confirmed 100 % accuracy in self-reporting of current and never smokers.
      Discordance in cotinine and smoking status was observed in 26 patients (15.0 %)
      reporting former tobacco use. Discordance in self-reported smoking was 12 times
      higher in recent (35.4 %) as compared with non-recent quitters (2.8 %). Combining
      disease site, pack-year history, and employment status predicted
      misrepresentation of tobacco use in 82.4 % of recent quitters. CONCLUSIONS: Self
      reported tobacco use may not accurately assess smoking status in newly diagnosed
      cancer patients. Patients who claim to have recently stopped smoking within the
      year prior to a cancer diagnosis and lung cancer patients may have a higher
      propensity to misrepresent tobacco use and may benefit from biochemical
      confirmation.

PMID- 23553612
TI  - Cervical softening occurs early in pregnancy: characterization of cervical
      stiffness in 100 healthy women using the aspiration technique.
AB  - OBJECTIVE: To quantitatively describe the evolution of ectocervical stiffness in
      normal pregnancy. METHODS: The stiffness of ectocervical tissue was measured by
      using the aspiration method. This non-invasive technique allows to safely and
      objectively determine the pressure required to displace cervical tissue to a
      predefined deformation level (pcl ). In this prospective study, 448 aspiration
      measurements were carried out on pregnant women (n = 50) at each of the eight
      routine pregnancy consultations and on nonpregnant subjects (reference, n = 50).
      pcl values were grouped as nonpregnant, first, second, third trimester, and
      postpartum. RESULTS: Stiffness in early pregnancy (first trimester) is
      significantly lower, by a factor >2 for the mean value than for the nonpregnant
      group. pcl continuously decreases during gestation, with significant differences
      between first and second trimester, but not between second and third trimester.
      After delivery, consistency is recovered to the level of early pregnancy.
      CONCLUSIONS: The aspiration method allows an objective description of the
      consistency of the ectocervix during pregnancy, indicating that the tissue
      softens already at the beginning of gestation, transforms continuously to lower
      consistency in the first two trimesters, stabilizes at a low level in the third
      trimester, and recovers its stiffness after delivery.

PMID- 23553613
TI  - Pre-operative urodynamics in women with stress urinary incontinence increases
      physician confidence, but does not improve outcomes.
AB  - AIMS: To determine if pre-operative urodynamic testing (UDS) affects physicians'
      diagnostic confidence and if physician confidence affects treatment outcomes at 1
      year. METHODS: The Value of Urodynamic Evaluation (ValUE) trial randomized 630
      women with predominant stress urinary incontinence (SUI) to office evaluation
      (OE) or OE plus UDS prior to surgery. After OE, physicians completed a checklist
      of five clinical diagnoses: SUI, overactive bladder (OAB) wet and dry, voiding
      dysfunction (VD), and intrinsic sphincter deficiency (ISD), and reported their
      confidence in each. Responses ranged from 1 to 5 with; 1 = "not very confident
      (<50%)" to 5 = "extremely confident (95 + %)." After UDS, investigators again
      rated their confidence in these five clinical diagnoses. Logistic regression
      analysis correlated physician confidence in diagnosis with treatment success.
      RESULTS: Of 315 women who received OE plus UDS, 294 had complete data. Confidence
      improved after UDS in patients with baseline SUI (4.52-4.63, P < 0.005), OAB-wet
      (3.55-3.75, P < 0.001), OAB-dry (3.55-3.68 P < 0.005), VD (3.81-3.95, P < 0.005),
      and suspected ISD (3.63-3.92, P < 0.001). Increased confidence after UDS was not
      associated with higher odds of treatment success although mean changes in
      confidence were slightly higher for those who achieved treatment success.
      Physician diagnoses shifted more from not confident to confident for ISD and OAB
      wet after UDS (McNemar's P-value <0.001 for both). CONCLUSIONS: In women
      undergoing UDS for predominant SUI, UDS increased physicians' confidence in their
      clinical diagnoses; however, this did not correlate with treatment success.

PMID- 23553614
TI  - Implementation of pro-poor exemption policy in Tanzania: policy versus reality.
AB  - Like many other African countries, Tanzania has been implementing user fee policy
      in its health sector since the early 1990s. Accompanying user fee, mechanisms
      were designed that exempted the poor and vulnerable groups of the society from
      paying user charges. Although studies on the implementation of exemption policies
      in Tanzania exist, very few have documented the actual process of translating
      exemption policies into actions-the process of implementation. Drawing from
      policy analysis and implementation theories, this paper documents the
      implementation of the waiver (need-based exemptions) policy in Tanzania. The
      findings indicate that waiver systems, while potentially effective in principle,
      were ineffective in implementation. Lack of specification of criteria by which
      the poor could be identified made policy implementers at different levels to
      implement the policy in their own style. Low level of public awareness about the
      existence of waiver mechanisms hindered the poor to demand exemptions.
      Furthermore, fear of loss of revenue at the health facilities and ineffective
      enforcement mechanisms provided little incentives for local government leaders
      and health workers to communicate the policy to beneficiaries. It is concluded
      from this study that to better achieve the objectives of the pro-poor exemption
      policy, it is important to engage policy implementers more actively in the
      management and implementation of policies. Additionally, it is imperative to
      understand the behaviour and practices of policy implementers, especially
      district health managers, health workers and village and ward leaders, who may
      react negatively to new policies and implement the policies in ways contrary to
      what policy makers had intended.

PMID- 23553615
TI  - Bacterial strains isolated from PCB-contaminated sediments and their use for
      bioaugmentation strategy in microcosms.
AB  - This study was focused on the characterization of 15 bacterial strains isolated
      from long-term PCB-contaminated sediment located at the Strazsky canal in eastern
      part of Slovakia, in the surroundings of a former PCB producer. PCB-degrading
      strains were isolated and identified as Microbacterium oleivorans,
      Stenotrophomonas maltophilia, Brevibacterium sp., Ochrobactrum anthropi,
      Pseudomonas mandelii, Rhodococcus sp., Achromobacter xylosoxidans,
      Stenotrophomonas sp., Ochrobactrum sp., Pseudomonas aeruginosa, and Starkeya
      novella by the 16S rRNA gene sequence phylogenetic analysis. This study presents
      a newly isolated bacterial strain S. novella with PCB-degrading ability in liquid
      medium as well as in sediment. For A. xylosoxidans, the bphA gene was identified.
      The best growth ability in the presence of all sole carbon sources (biphenyl and
      PCBs vapor) was obtained for Ochrobactrum sp. and Rhodococcus sp. Uncultured
      Achromobacter sp. showed the highest potential for bioaugmentation of PCB
      contaminated sediment. 

PMID- 23553616
TI  - Loss of p47phox subunit enhances susceptibility to biomechanical stress and heart
      failure because of dysregulation of cortactin and actin filaments.
AB  - RATIONALE: The classic phagocyte nicotinamide adenine dinucleotide phosphate
      oxidase (gp91(phox) or Nox2) is expressed in the heart. Nox2 activation requires
      membrane translocation of the p47(phox) subunit and is linked to heart failure.
      We hypothesized that loss of p47(phox) subunit will result in decreased reactive
      oxygen species production and resistance to heart failure. OBJECTIVE: To define
      the role of p47(phox) in pressure overload-induced biomechanical stress. METHODS
      AND RESULTS: Eight-week-old male p47(phox) null (p47(phox) knockout [KO]), Nox2
      null (Nox2KO), and wild-type mice were subjected to transverse aortic
      constriction-induced pressure overload. Contrary to our hypothesis, p47(phox)KO
      mice showed markedly worsened systolic dysfunction in response to pressure
      overload at 5 and 9 weeks after transverse aortic constriction compared with wild
      type-transverse aortic constriction mice. We found that biomechanical stress
      upregulated N-cadherin and beta-catenin in p47(phox)KO hearts but disrupted the
      actin filament cytoskeleton and reduced phosphorylation of focal adhesion kinase.
      p47(phox) interacts with cytosolic cortactin by coimmunoprecipitation and double
      immunofluorescence staining in murine and human hearts and translocated to the
      membrane on biomechanical stress where cortactin interacted with N-cadherin,
      resulting in adaptive cytoskeletal remodeling. However, p47(phox)KO hearts showed
      impaired interaction of cortactin with N-cadherin, resulting in loss of
      biomechanical stress-induced actin polymerization and cytoskeletal remodeling. In
      contrast, Nox2 does not interact with cortactin, and Nox2-deficient hearts were
      protected from pressure overload-induced adverse myocardial and intracellular
      cytoskeletal remodeling. CONCLUSIONS: We showed a novel role of p47(phox) subunit
      beyond and independent of nicotinamide adenine dinucleotide phosphate oxidase
      activity as a regulator of cortactin and adaptive cytoskeletal remodeling,
      leading to a paradoxically enhanced susceptibility to biomechanical stress and
      heart failure.

PMID- 23553617
TI  - Direct exfoliation of graphite to graphene in aqueous media with
      diazaperopyrenium dications.
AB  - The 2,9-dimethyldiazaperopyrenium dication can be made from a ubiquitous and
      inexpensive feedstock in three simple steps as its chloride salt. When mixed with
      powdered graphite at 23  degrees C, this behemoth of a molecular compound
      exfoliates graphite to graphene in water under mild conditions.

PMID- 23553618
TI  - Effects of a traditional fermented grape-based drink 'hardaliye' on antioxidant
      status of healthy adults: a randomized controlled clinical trial.
AB  - BACKGROUND: The antioxidative effects of the traditional grape-based beverage,
      hardaliye, were investigated with a 40-day randomized controlled clinical trial
      on 89 healthy adults. Subjects were randomly divided into three groups: high
      hardaliye (HH), low hardaliye (LH) and control group. HH and LH groups consumed
      500 mL and 250 mL hardaliye per day, respectively, and the control group did not
      consume any hardaliye. Dien conjugate (DC), malondialdehyde (MDA), vitamin C,
      total antioxidant capacity (TAC) and homocysteine concentrations were measured in
      fasting blood samples collected at baseline and after intervention. RESULTS:
      Significant decreases in DC, MDA and homocysteine concentrations were observed in
      HH and LH groups (P < 0.001) after intervention, whereas the control group showed
      no change. The reduction in homocysteine was significantly different between HH
      and LH groups (P < 0.001), except for DC and MDA. TAC and vitamin C were slightly
      increased; however, the change was not statistically significant. CONCLUSION:
      Dietary supplementation with hardaliye affect the MDA, DC and homocysteine levels
      in blood, possibly due to the presence of antioxidant compounds. Dose response
      was only observed for homocysteine. Further studies need to be performed to
      assess the effects on antioxidant capacity.

PMID- 23553619
TI  - Incidence and costs of adverse drug reactions in a tertiary care pediatric
      intensive care unit.
AB  - Adverse drug reactions (ADRs) increase morbidity, mortality, and hospital costs
      in children treated in the Pediatric Intensive Care Unit (PICU). Few studies have
      reported the incidence and risk factors of ADRs in PICU. Our study aimed to
      evaluate incidence, risk factors, and economic burden of ADRs in PICU. An
      intensive ADR surveillance was conducted at the PICU of Children's Hospital of
      Michigan between November 1, 2010 and May 31, 2011. A trigger list was used to
      screen for suspected ADR cases. Of the 697 consecutive PICU admissions reviewed,
      13.1% experienced at least one episode of ADR. The ADR incidence was 22% in
      patients with cardiovascular (CV) surgery and 11.5% in other patients. The most
      frequently detected ADR was electrolyte imbalance associated with diuretic
      exposure. Mean age at admission was 4 years (interquartile range: 9 months-13
      years). Risk factors for ADR included young age (<1 year), Pediatric Risk of
      Mortality (PRISM) score upon admission >=3, and administration of >=16
      medications. ADRs increased total ICU costs by 3.5-fold and length of ICU stay by
      3.8-fold. Increased ADR surveillance of high risk patients in conjunction with
      early intervention may reduce drug related morbidity and costs in the PICU.

PMID- 23553620
TI  - Prognostic significance of syndecan-1 expression in squamous cell carcinoma of
      the tonsil.
AB  - BACKGROUND: Syndecan-1 (SDC1) is reported to modulate several key processes of
      tumorigenesis and to show variable expression in many cancers. The cause of these
      variations in expression is not known to date. In this study, we compared SDC1
      status with clinicopathologic parameters to evaluate the prognostic implications
      of SDC1 status on squamous cell carcinoma (SCC) of the tonsil. METHODS: In 56
      cases of tonsillar SCC, we screened SDC1 expression using immunohistochemistry
      and analyzed the relationships between SDC1 expression and clinicopathological
      parameters. To identify the cause of the changes in SDC1 expression seen in
      tumors, we measured the gene dosage of SDC1 in tumor cells using fluorescent in
      situ hybridization. RESULTS: SDC1 expression was found in cancer cells in 36
      cases (64.3 %) of tonsillar SCC. It was associated with lymph node metastasis (p
      = 0.010) and a positive surgical resection margin (p = 0.014). On the other hand,
      it was not significantly correlated with sex, age, smoking status, degree of
      differentiation, T stage, or distant metastasis. We could not find any copy
      number variation of SDC1 in the cases showing increased SDC1 immunopositivity. In
      addition, strong SDC1 expression in the tumor cells predicted a shorter overall
      survival (p = 0.020, log-rank). CONCLUSIONS: We showed that SDC1 expression is
      associated with N stage and the status of resection margin involvement in SCC of
      the tonsil. With respect to survival, there were unfavorable outcomes in cases
      with SDC1 positivity. More studies are needed to better understand the role of
      SDC1 in the progression and invasiveness of tonsillar SCC.

PMID- 23553621
TI  - Quantification of JAK2V617F mutation by next-generation sequencing technology.

PMID- 23553622
TI  - Tanshinone IIA inhibits breast cancer stem cells growth in vitro and in vivo
      through attenuation of IL-6/STAT3/NF-kB signaling pathways.
AB  - Cancer stem cells (CSCs) are maintained by inflammatory cytokines and signaling
      pathways. Tanshinone IIA (Tan-IIA) possesses anti-cancer and anti-inflammatory
      activities. The purpose of this study is to confirm the growth inhibition effect
      of Tan-IIA on human breast CSCs growth in vitro and in vivo and to explore the
      possible mechanism of its activity. Human breast CSCs were enriched and expanded
      under serum-free mammosphere culture condition, and identified through
      mammosphere formation, toluidine blue staining, immunofluorescence staining, and
      flow cytometry analysis of stemness markers of CD44/CD24 and ALDH, and
      tumorigenecity in vivo; the growth inhibition effect of Tan-IIA on human breast
      CSCs in vitro were tested by cell proliferation and mammosphere formation assays;
      inflammatory signaling pathway related protein expression in response to Tan-IIA,
      IL-6, STAT3, phospho-STAT3 (Tyr705), NF-kappaBp65 in cytoplasm and nucleus and
      cyclin D1 were evaluated with Western blotting; the growth inhibition effect of
      Tan-IIA on human breast CSCs growth were tested in vivo. A useful model of human
      breast CSCs for researching and developing the agents targeting CSCs was
      established. After Tan-IIA treatment, cell proliferation and mammosphere
      formation of CSCs were decreased significantly; the expression levels of IL-6,
      STAT3, phospho-STAT3 (Tyr705), NF-kappaBp65 in nucleus and cyclin D1 proteins
      were decreased significantly; the tumor growth and mean tumor weight were reduced
      significantly. Tan-IIA has the potential to target and kill CSCs, and can inhibit
      human breast CSCs growth both in vitro and in vivo through attenuation of IL
      6/STAT3/NF-kB signaling pathways.

PMID- 23553623
TI  - Increasing body mass index, blood pressure, and Acanthosis Nigricans
      abnormalities in school-age children.
AB  - This retrospective quantitative study examined the relationships among gender,
      Acanthosis Nigricans (AN), body mass index (BMI), and blood pressure (BP) in
      children attending school Grades 1-9 in Southwest Texas. Of the 34,897 health
      screening records obtained for the secondary analysis, 32,788 were included for
      the study. A logistic regression analysis was carried out with AN as the
      dependent variable, with year, gender, BMI, and BP as independent variables. The
      results indicate that the rate of children in each grade with three positive
      markers increased 2% during a 3-year period between 2008 and 2010. In the 5-year
      period between 2005 and 2010, a clear trend of significantly higher numbers of
      children with both AN and BMI markers was apparent. Gender played a significant
      role as females were more likely to have the AN marker than males. Further study
      is indicated based on the increasing trend of school-age children in Texas with
      positive markers for AN, increased BMI and BP. 

PMID- 23553624
TI  - Collaborative care for children: a grand rounds presentation.
AB  - At the end of the 2011-2012 school year, two collaborative initiatives took place
      in Springfield, MA, between the public school system and Baystate Medical Center,
      an affiliate of Tufts University. The success of these initiatives was
      highlighted during grand rounds that featured academic medical center physicians
      and nurses as well as public school nurses. The program highlighted care of urban
      children with one of two chronic diseases, type 1 diabetes or asthma. Although
      the treatment and care of both these chronic childhood illnesses vary greatly, it
      is evident that primary care providers, school nurses, and students can benefit
      from increased collaboration, communication, and understanding of each other's
      roles. The partnerships were developed in an effort to overcome health care
      disparities that can and do exist in urban school districts such as Springfield,
      MA. In this commentary, we discuss important outcomes that resulted from the
      joint presentation at grand rounds. 

PMID- 23553625
TI  - Behind closed doors: school nurses and sexual education.
AB  - School nurses can play a key role in providing sexual education in schools.
      However, they often face barriers from the school administration and concerned
      parents. Additionally, school nurses may have limited formal preparation in
      managing sexual health issues. This study used a descriptive qualitative method
      to explore the school nurses' experiences with facilitators and barriers to
      providing sexual education. Eighteen nurses from 12 Massachusetts high schools
      were interviewed. Results showed that the school nurses do not provide formal
      sexual education at their schools but frequently conduct informal sessions.
      School nurses reported that students needed more sexual health information, yet
      there was no collaboration with the school health teachers. Common barriers
      included lack of privacy and time, confidentiality issues, and fear of conflict.
      Nurses working in communities with high teen pregnancy rates reported more
      barriers. The findings can inform the development of policies and practices for
      sexual education by school nurses. 

PMID- 23553626
TI  - The unique disulfide bond-stabilized W1 beta4-beta1 loop in the alpha4 beta
      propeller domain regulates integrin alpha4beta7 affinity and signaling.
AB  - Integrin alpha4beta7 mediates rolling and firm adhesion of lymphocytes pre- and
      post-activation, which is distinct from most integrins only mediating firm cell
      adhesion upon activation. This two-phase cell adhesion suggests a unique
      molecular basis for the dynamic interaction of alpha4beta7 with its ligand,
      mucosal addressin cell adhesion molecule 1 (MAdCAM-1). Here we report that a
      disulfide bond-stabilized W1 beta4-beta1 loop in alpha4 beta-propeller domain
      plays critical roles in regulating integrin alpha4beta7 affinity and signaling.
      Either breaking the disulfide bond or deleting the disulfide bond-occluded
      segment in the W1 beta4-beta1 loop inhibited rolling cell adhesion supported by
      the low-affinity interaction between MAdCAM-1 and inactive alpha4beta7 but
      negligibly affected firm cell adhesion supported by the high-affinity interaction
      between MAdCAM-1 and Mn(2+)-activated alpha4beta7. Additionally, disrupting the
      disulfide bond or deleting the disulfide bond-occluded segment not only blocked
      the conformational change and activation of alpha4beta7 triggered by talin or
      phorbol-12-myristate-13-acetate via inside-out signaling but also disrupted
      integrin-mediated outside-in signaling and impaired phosphorylation of focal
      adhesion kinase and paxillin. Thus, these findings reveal a particular molecular
      basis for alpha4beta7-mediated rolling cell adhesion and a novel regulatory
      element of integrin affinity and signaling.

PMID- 23553627
TI  - DNA-dependent activator of interferon-regulatory factors (DAI) promotes lupus
      nephritis by activating the calcium pathway.
AB  - BACKGROUND: Macrophage M2b polarization conferred by self-DNA immunization
      initiates and propagates lupus nephritis. RESULTS: Knockdown of DNA-dependent
      activator of interferon-regulatory factors (DAI) ameliorates SLE syndrome via
      blunting macrophage M2b polarization. CONCLUSION: DAI functions as a DNA sensor
      in self-DNA-induced macrophage M2b polarization and lupus nephritis.
      SIGNIFICANCE: We disclose the mechanism by which self-DNA induces macrophage M2b
      polarization and lupus nephritis DNA-dependent activator of interferon-regulatory
      factors (DAI) functions as a cytoplasmic DNA sensor that activates the innate
      immune system. We previously found that activated lymphocyte-derived self
      apoptotic DNA (ALD-DNA) immunization led to pathological macrophage activation
      and M2b polarization, which could initiate and propagate murine lupus nephritis.
      However, the specific DNA sensor(s) as well as underlying molecular mechanisms
      involved in ALD-DNA-induced macrophage M2b polarization in systemic lupus
      erythematosus (SLE) disease remains unknown. In this study, we reported that DAI
      expression was significantly increased in SLE patients as well as in lupus mice.
      Gain- and loss-of-function studies revealed that DAI was involved in ALD-DNA
      induced macrophage activation and M2b polarization. Moreover, ALD-DNA notably
      induced dimerization/oligomerization of DAI and consequently activation of
      nuclear factor kappaB (NF-kappaB) and interferon regulatory factor 3 (IRF3)
      signaling pathways via calcium signaling, resulting in macrophage activation and
      M2b polarization. More importantly, blockade of DAI in vivo or selective
      knockdown of DAI in macrophages could ameliorate SLE syndrome via blunting
      macrophage M2b polarization and inhibiting inflammatory response in lupus mice.
      Our results suggest that DAI could function as a DNA sensor and a regulator in
      ALD-DNA-induced macrophage M2b polarization and lupus nephritis, providing the
      possible molecular mechanisms involved in ALD-DNA-induced macrophage M2b
      polarization in SLE disease and making DAI as a potential therapeutic target for
      the treatment of SLE.

PMID- 23553628
TI  - Hemolymph melanization in the silkmoth Bombyx mori involves formation of a high
      molecular mass complex that metabolizes tyrosine.
AB  - The phenoloxidase (PO) cascade regulates the melanization of blood (hemolymph) in
      insects and other arthropods. Most studies indicate that microbial elicitors
      activate the PO cascade, which results in processing of the zymogen PPO to PO. PO
      is then thought to oxidize tyrosine and o-diphenols to quinones, which leads to
      melanin. However, different lines of investigation raise questions as to whether
      these views are fully correct. Here we report that hemolymph from the silkmoth,
      Bombyx mori, rapidly melanizes after collection from a wound site. Prior studies
      indicated that in vitro activated PPO hydroxylates Tyr inefficiently. Measurement
      of in vivo substrate titers, however, suggested that Tyr was the only PO
      substrate initially present in B. mori plasma and that it is rapidly metabolized
      by PO. Fractionation of plasma by gel filtration chromatography followed by
      bioassays indicated that melanization activity was primarily associated with a
      high mass complex (~670 kDa) that contained PO. The prophenoloxidase-activating
      protease inhibitor Egf1.0 blocked formation of this complex and Tyr metabolism,
      but the addition of phenylthiourea to plasma before fractionation enhanced
      complex formation and Tyr metabolism. Mass spectrometry analysis indicated that
      the complex contained PO plus other proteins. Taken together, our results
      indicate that wounding alone activates the PO cascade in B. mori. They also
      suggest that complex formation is required for efficient use of Tyr as a
      substrate.

PMID- 23553629
TI  - The signal peptide of the tumor-shared antigen midkine hosts CD4+ T cell
      epitopes.
AB  - BACKGROUND: The CD4 T cell response to the tumor antigen Midkine was unknown.
      RESULTS: Most of the T cell response to Midkine relies on T cell epitopes
      contained in its signal peptide. CONCLUSION: The signal peptide of Midkine is
      accessible to HLA class II pathway for CD4 T cell presentation. SIGNIFICANCE: It
      is a new function for signal peptides to contribute to tumor-specific CD4 T cell
      response. Because of the key role of CD4 T cell response in immunity to tumors,
      we investigated the CD4(+) T cell response to the recently identified tumor
      antigen Midkine (MDK). By weekly stimulations of T lymphocytes harvested from
      seven HLA-DR-typed healthy donors, we derived CD4(+) T cell lines specific for
      eight MDK peptides. Most of the T cell lines reacted with the peptides 9-23 and
      14-28, located in and overlapping the MDK signal peptide, respectively.
      Accordingly, the MDK signal peptide appeared to be rich in good binders to common
      HLA-DR molecules. The peptide 9-23-specific T cell lines were specifically
      stimulated by autologous dendritic cells loaded with lysates of MDK-transfected
      cells or with lysates of tumor cells naturally expressing the MDK protein. One T
      cell line was stimulated by HLA-compatible MDK-transfected tumor cells. By
      contrast, the peptide 14-28-specific T cell lines were not stimulated in any of
      these conditions. Our data demonstrate that CD4(+) T cell epitopes present in the
      signal peptide can be accessible to recognition by CD4(+) T cells and may
      therefore contribute to tumor immunity, whereas a peptide overlapping the
      junction between the signal peptide and the mature protein is not.

PMID- 23553630
TI  - Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis.
AB  - The accumulation of long-chain fatty acids (LCFAs) in non-adipose tissues results
      in lipid-induced cytotoxicity (or lipoapoptosis). Lipoapoptosis has been proposed
      to play an important role in the pathogenesis of several metabolic diseases,
      including non-alcoholic fatty liver disease, diabetes mellitus, and
      cardiovascular disease. In this report, we demonstrate a novel role for caspase-2
      as an initiator of lipoapoptosis. Using a metabolomics approach, we discovered
      that the activation of caspase-2, the initiator of apoptosis in Xenopus egg
      extracts, is associated with an accumulation of LCFA metabolites. Metabolic
      treatments that blocked the buildup of LCFAs potently inhibited caspase-2
      activation, whereas adding back an LCFA in this scenario restored caspase
      activation. Extending these findings to mammalian cells, we show that caspase-2
      was engaged and activated in response to treatment with the saturated LCFA
      palmitate. Down-regulation of caspase-2 significantly impaired cell death induced
      by saturated LCFAs, suggesting that caspase-2 plays a pivotal role in lipid
      induced cytotoxicity. Together, these findings reveal a previously unknown role
      for caspase-2 as an initiator caspase in lipoapoptosis and suggest that caspase-2
      may be an attractive therapeutic target for inhibiting pathological lipid-induced
      apoptosis.

PMID- 23553631
TI  - Molecular bases of multimodal regulation of a fungal transient receptor potential
      (TRP) channel.
AB  - Multimodal activation by various stimuli is a fundamental characteristic of TRP
      channels. We identified a fungal TRP channel, TRPGz, exhibiting activation by
      hyperosmolarity, temperature increase, cytosolic Ca(2+) elevation, membrane
      potential, and H2O2 application, and thus it is expected to represent a
      prototypic multimodal TRP channel. TRPGz possesses a cytosolic C-terminal domain
      (CTD), primarily composed of intrinsically disordered regions with some
      regulatory modules, a putative coiled-coil region and a basic residue cluster.
      The CTD oligomerization mediated by the coiled-coil region is required for the
      hyperosmotic and temperature increase activations but not for the tetrameric
      channel formation or other activation modalities. In contrast, the basic cluster
      is responsible for general channel inhibition, by binding to phosphatidylinositol
      phosphates. The crystal structure of the presumed coiled-coil region revealed a
      tetrameric assembly in an offset spiral rather than a canonical coiled-coil. This
      structure underlies the observed moderate oligomerization affinity enabling the
      dynamic assembly and disassembly of the CTD during channel functions, which are
      compatible with the multimodal regulation mediated by each functional module.

PMID- 23553632
TI  - The N and C termini of ZO-1 are surrounded by distinct proteins and functional
      protein networks.
AB  - BACKGROUND: Biotin ligase tagging with ZO-1 was applied to identify a more
      complete tight junction proteome. RESULTS: Identical but also different proteins
      and functional networks were identified near the N and C ends of ZO-1.
      CONCLUSION: The ends of ZO-1 are embedded in different functional subcompartments
      of the tight junction. SIGNIFICANCE: Biotin tagging with ZO-1 expands the tight
      junction proteome and defines subcompartments of the junction. The proteins and
      functional protein networks of the tight junction remain incompletely defined.
      Among the currently known proteins are barrier-forming proteins like occludin and
      the claudin family; scaffolding proteins like ZO-1; and some cytoskeletal,
      signaling, and cell polarity proteins. To define a more complete list of proteins
      and infer their functional implications, we identified the proteins that are
      within molecular dimensions of ZO-1 by fusing biotin ligase to either its N or C
      terminus, expressing these fusion proteins in Madin-Darby canine kidney
      epithelial cells, and purifying and identifying the resulting biotinylated
      proteins by mass spectrometry. Of a predicted proteome of ~9000, we identified
      more than 400 proteins tagged by biotin ligase fused to ZO-1, with both identical
      and distinct proteins near the N- and C-terminal ends. Those proximal to the N
      terminus were enriched in transmembrane tight junction proteins, and those
      proximal to the C terminus were enriched in cytoskeletal proteins. We also
      identified many unexpected but easily rationalized proteins and verified partial
      colocalization of three of these proteins with ZO-1 as examples. In addition,
      functional networks of interacting proteins were tagged, such as the basolateral
      but not apical polarity network. These results provide a rich inventory of
      proteins and potential novel insights into functions and protein networks that
      should catalyze further understanding of tight junction biology. Unexpectedly,
      the technique demonstrates high spatial resolution, which could be generally
      applied to defining other subcellular protein compartmentalization.

PMID- 23553634
TI  - Cyclic AMP-dependent protein lysine acylation in mycobacteria regulates fatty
      acid and propionate metabolism.
AB  - Acetylation of lysine residues is a posttranslational modification that is used
      by both eukaryotes and prokaryotes to regulate a variety of biological processes.
      Here we identify multiple substrates for the cAMP-dependent protein lysine
      acetyltransferase from Mycobacterium tuberculosis (KATmt). We demonstrate that a
      catalytically important lysine residue in a number of FadD (fatty acyl CoA
      synthetase) enzymes is acetylated by KATmt in a cAMP-dependent manner and that
      acetylation inhibits the activity of FadD enzymes. A sirtuin-like enzyme can
      deacetylate multiple FadDs, thus completing the regulatory cycle. Using a strain
      deleted for the KATmt ortholog in Mycobacterium bovis Bacillus Calmette-Guerin
      (BCG), we show for the first time that acetylation is dependent on intracellular
      cAMP levels. KATmt can utilize propionyl CoA as a substrate and, therefore, plays
      a critical role in alleviating propionyl CoA toxicity in mycobacteria by
      inactivating acyl CoA synthetase (ACS). The precision by which mycobacteria can
      regulate the metabolism of fatty acids in a cAMP-dependent manner appears to be
      unparalleled in other biological organisms and is ideally suited to adapt to the
      complex environment that pathogenic mycobacteria experience in the host.

PMID- 23553633
TI  - Enhanced asynchronous Ca(2+) oscillations associated with impaired glutamate
      transport in cortical astrocytes expressing Fmr1 gene premutation expansion.
AB  - BACKGROUND: FMR1 CGG expansion repeats in the premutation range have not been
      linked to astrocyte pathophysiology. RESULTS: Premutation cortical astrocytes
      display decreased Glu transporter expression/activity and enhanced asynchronous
      Ca(2+) oscillations. CONCLUSION: Glu transport and Ca(2+) signaling defects in
      premutation astrocytes could contribute to FXTAS neuropathology. SIGNIFICANCE:
      Premutation astrocytes may have an etiological role in FXTAS neuropathology.
      Premutation CGG repeat expansions (55-200 CGG repeats; preCGG) within the fragile
      X mental retardation 1 (FMR1) gene can cause fragile X-associated tremor/ataxia
      syndrome. Defects in early neuronal migration and morphology,
      electrophysiological activity, and mitochondria trafficking have been described
      in a premutation mouse model, but whether preCGG mutations also affect astrocyte
      function remains unknown. PreCGG cortical astrocytes (~170 CGG repeats) displayed
      3-fold higher Fmr1 mRNA and 30% lower FMR1 protein (FMRP) when compared with WT.
      PreCGG astrocytes showed modest reductions in expression of glutamate (Glu)
      transporters GLT-1 and GLAST and attenuated Glu uptake (p < 0.01). Consistent
      with astrocyte cultures in vitro, aged preCGG mice cerebral cortex also displayed
      reduced GLAST and GLT-1 expression. Approximately 65% of the WT and preCGG
      cortical astrocytes displayed spontaneous asynchronous Ca(2+) oscillations.
      PreCGG astrocytes exhibited nearly 50% higher frequency of asynchronous Ca(2+)
      oscillations (p < 0.01) than WT, a difference mimicked by chronic exposure of WT
      astrocytes to l-trans-pyrrolidine-2,4-dicarboxylic acid (l-trans-PDC) or by
      partial suppression of GLAST using siRNA interference. Acute challenge with Glu
      augmented the frequency of Ca(2+) oscillations in both genotypes. Additionally,
      10 MUm Glu elicited a sustained intracellular Ca(2+) rise in a higher portion of
      preCGG astrocytes when compared with WT. Pharmacological studies showed that
      mGluR5, but not NMDA receptor, contributed to Glu hypersensitivity in preCGG
      astrocytes. These functional defects in preCGG astrocytes, especially in Glu
      signaling, may contribute to fragile X-associated tremor/ataxia syndrome
      neuropathology.

PMID- 23553637
TI  - Sex differences in the effect of four second-generation antipsychotics on QTc
      interval in patients with schizophrenia.
AB  - OBJECTIVE: We examined sex differences in the effect of olanzapine (OLZ),
      risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT
      (QTc) intervals among 222 patients with schizophrenia. METHODS: Subjects were
      patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n =
      60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were
      conducted, and the QT interval was corrected using Bazett's correction formula.
      RESULTS: The mean QTc interval of the QTP group was significantly longer than
      that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval
      of the OLZ group was also significantly longer than that of the RIS group (p =
      0.006). In female participants, the difference in the mean QTc interval among the
      four second-generation antipsychotic (SGA) groups was statistically significant
      (p = 0.002), whereas in male patients, there was no significant difference in the
      mean QTc interval among the four SGA groups. Post hoc analyses showed that sex
      differences in QTc interval were observed only in OLZ treatment group (p =
      0.007). CONCLUSION: To our knowledge, this is the first study to demonstrate sex
      differences in the effect of four SGAs on the QTc interval.

PMID- 23553638
TI  - The effect of steroids in combination with optic nerve decompression surgery in
      traumatic optic neuropathy.
AB  - OBJECTIVES/HYPOTHESIS: Traumatic optic neuropathy (TON) is an important cause of
      severe visual impairment following blunt or penetrating head trauma. Treatment
      options include steroids, decompression, or both. Studies have failed to show a
      clear benefit for either steroids or surgery or a combined therapy. This study
      describes the visual outcome in surgically managed patients with or without
      steroid treatment. STUDY DESIGN: Retrospective analysis. METHODS: In a
      retrospective chart review we included patients (n = 42) with TON who were
      managed with optic nerve decompression surgery with or without steroids.
      Comparison of initial and final visual acuity was the primary outcome parameter.
      RESULTS: In 42 consecutive patients, steroids were used in 21 cases (50%). Ten
      patients received a high-dose systemic regimen of more than 500 mg
      methylprednisolone initial dose, and 11 patients were treated with a lower dose.
      The overall visual improvement rate was 33%, no change was noted in 50%, and no
      outcome data were available in 17%. The visual improvement rate of patients
      treated with decompression surgery and steroids was lower (29%, 6 of 21) than
      those treated with surgery alone (53%, 8 of 15). Comparing both groups,
      additional steroids had no beneficial effect on the visual outcome (P = .97).
      There was no case with a deterioration of visual function due to therapy.
      CONCLUSIONS: In patients with traumatic optic neuropathy who were treated with
      optic nerve decompression surgery, steroids had no beneficial effect on the
      visual outcome. LEVEL OF EVIDENCE: 2c.

PMID- 23553635
TI  - Capacity and plasticity of potassium channels and high-affinity transporters in
      roots of barley and Arabidopsis.
AB  - The role of potassium (K(+)) transporters in high- and low-affinity K(+) uptake
      was examined in roots of intact barley (Hordeum vulgare) and Arabidopsis
      (Arabidopsis thaliana) plants by use of (42)K radiotracing, electrophysiology,
      pharmacology, and mutant analysis. Comparisons were made between results from
      barley and five genotypes of Arabidopsis, including single and double knockout
      mutants for the high-affinity transporter, AtHAK5, and the Shaker-type channel,
      AtAKT1. In Arabidopsis, steady-state K(+) influx at low external K(+)
      concentration ([K(+)]ext = 22.5 um) was predominantly mediated by AtAKT1 when
      high-affinity transport was inhibited by ammonium, whereas in barley, by
      contrast, K(+) channels could not operate below 100 um. Withdrawal of ammonium
      resulted in an immediate and dramatic stimulation of K(+) influx in barley,
      indicating a shift from active to passive K(+) uptake at low [K(+)]ext and
      yielding fluxes as high as 36 umol g (root fresh weight)(-1) h(-1) at 5 mm
      [K(+)]ext, among the highest transporter-mediated K(+) fluxes hitherto reported.
      This ammonium-withdrawal effect was also established in all Arabidopsis lines
      (the wild types, atakt1, athak5, and athak5 atakt1) at low [K(+)]ext, revealing
      the concerted involvement of several transport systems. The ammonium-withdrawal
      effect coincided with a suppression of K(+) efflux and a significant
      hyperpolarization of the plasma membrane in all genotypes except athak5 atakt1,
      could be sustained over 24 h, and resulted in increased tissue K(+) accumulation.
      We discuss key differences and similarities in K(+) acquisition between two
      important model systems and reveal novel aspects of K(+) transport in planta.

PMID- 23553639
TI  - Two sides of the same coin: sodium homeostasis and signaling in astrocytes under
      physiological and pathophysiological conditions.
AB  - The intracellular sodium concentration of astrocytes is classically viewed as
      being kept under tight homeostatic control and at a relatively stable level under
      physiological conditions. Indeed, the steep inwardly directed electrochemical
      gradient for sodium, generated by the Na+/K+-ATPase, contributes to maintain the
      electrochemical gradient of K+ and the highly K+-based negative membrane
      potential, and is a central element in energizing membrane transport. As such it
      is tightly coupled to the homeostasis of extra- and intracellular potassium,
      calcium or pH and to the reuptake of transmitters such as glutamate. Recent
      studies, however, have demonstrated that this picture is far too simplistic. It
      is now firmly established that transmitters, most notably glutamate, and
      excitatory neuronal activity evoke long-lasting sodium transients in astrocytes,
      the properties of which are distinctly different from those of activity-related
      glial calcium signals. From these studies, it emerges that sodium homeostasis and
      signaling are two sides of the same coin: sodium-dependent transporters,
      primarily known for their role in ion regulation and homeostasis, also generate
      relevant ion signals during neuronal activity. The functional consequences of
      activity-related sodium transients are manifold and are just coming into view,
      enabling surprising and important new insights into astrocyte function and neuron
      glia interaction in the brain. The present review will highlight current
      knowledge about the mechanisms that contribute to sodium homeostasis in
      astrocytes, present recent data on the spatial and temporal properties of
      activity-related glial sodium signals and discuss their functional consequences
      with a special emphasis on pathophysiological conditions.

PMID- 23553636
TI  - Ethylene Response Factor6 acts as a central regulator of leaf growth under water
      limiting conditions in Arabidopsis.
AB  - Leaf growth is a complex developmental process that is continuously fine-tuned by
      the environment. Various abiotic stresses, including mild drought stress, have
      been shown to inhibit leaf growth in Arabidopsis (Arabidopsis thaliana), but the
      underlying mechanisms remain largely unknown. Here, we identify the redundant
      Arabidopsis transcription factors ETHYLENE RESPONSE FACTOR5 (ERF5) and ERF6 as
      master regulators that adapt leaf growth to environmental changes. ERF5 and ERF6
      gene expression is induced very rapidly and specifically in actively growing
      leaves after sudden exposure to osmotic stress that mimics mild drought.
      Subsequently, enhanced ERF6 expression inhibits cell proliferation and leaf
      growth by a process involving gibberellin and DELLA signaling. Using an ERF6
      inducible overexpression line, we demonstrate that the gibberellin-degrading
      enzyme GIBBERELLIN 2-OXIDASE6 is transcriptionally induced by ERF6 and that,
      consequently, DELLA proteins are stabilized. As a result, ERF6 gain-of-function
      lines are dwarfed and hypersensitive to osmotic stress, while the growth of
      erf5erf6 loss-of-function mutants is less affected by stress. Besides its role in
      plant growth under stress, ERF6 also activates the expression of a plethora of
      osmotic stress-responsive genes, including the well-known stress tolerance genes
      STZ, MYB51, and WRKY33. Interestingly, activation of the stress tolerance genes
      by ERF6 occurs independently from the ERF6-mediated growth inhibition. Together,
      these data fit into a leaf growth regulatory model in which ERF5 and ERF6 form a
      missing link between the previously observed stress-induced 1-aminocyclopropane-1
      carboxylic acid accumulation and DELLA-mediated cell cycle exit and execute a
      dual role by regulating both stress tolerance and growth inhibition.

PMID- 23553640
TI  - Axonal excitability during ischemia in MELAS.
AB  - INTRODUCTION: In mitochondrial disease, it is likely that energy substrate
      depletion leads to paralysis of ATPase-dependent pumps, resulting in membrane
      depolarization. Axonal depolarization has been demonstrated in a crisis, but not
      in the resting state. We, therefore, stressed axons using ischemia to see if this
      would reveal abnormal responses, as occurs in diabetes mellitus. METHODS:
      Excitability of median nerve axons at the wrist was studied in 13 patients with
      MELAS (6 with glucose intolerance) and 17 control subjects in response to
      ischemia due to inflation of a cuff around the arm for 10 min. RESULTS: There
      were no significant differences in preischemic measures of axonal excitability or
      in the intra- and postischemic responses. CONCLUSIONS: Although depolarization
      has been noted to occur spontaneously during a crisis, we could not demonstrate a
      defect of axonal ATP-dependent mechanisms. The mechanisms underlying axonal
      excitability and neuropathy in diabetes may not apply to MELAS.

PMID- 23553641
TI  - Interaction of the iron(II) cage complexes with proteins: protein fluorescence
      quenching study.
AB  - Interaction of the iron(II) mono- and bis-clathrochelates with bovine serum
      albumin (BSA), beta-lactoglobulin, lysozyme and insulin was studied by the steady
      state and time-resolved fluorescent spectroscopies. These cage complexes do not
      make significant impact on fluorescent properties of beta-lactoglobulin, lysozyme
      and insulin. At the same time, the monoclathrochelates strongly quench a
      fluorescence intensity of BSA and substantially decrease its excited state
      lifetime due to their binding to this protein. This occurs due to the excitation
      energy transfer from a tryptophan residue to a cage molecule or/and to the change
      of the tryptophan nearest environment caused by either clathrochelate binding or
      an alteration of the BSA conformation. The effect of the iron(II) bis
      clathrochelate on BSA fluorescence is much weaker as compared to its
      monomacrobicyclic analogs as a result of an increase in its size. 

PMID- 23553644
TI  - Confidence intervals for confirmatory adaptive two-stage designs with treatment
      selection.
AB  - The construction of adequate confidence intervals for adaptive two-stage designs
      remains an area of ongoing research. We propose a conditional likelihood-based
      approach to construct a Wald confidence interval and two confidence intervals
      based on inverting the likelihood ratio test, one of them using first-order
      inference methods and the second one using higher order inference methods. The
      coverage probabilities of these confidence intervals, and also the average bias
      and mean square error of the corresponding point estimates, compare favorably
      with other available techniques. A small simulation study is used to evaluate the
      performance of the new methods. We investigate other extensions of practical
      interest for normal endpoints and illustrate them using real data, including the
      selection of more than one treatment for the second stage, selection rules based
      on both efficacy and safety endpoints, and the inclusion of a control/placebo
      arm. The new method also allows adjustment for covariates, and has been extended
      to deal with binomial data and other distributions from the exponential family.
      Although conceptually simple, the new methods have a much wider scope than the
      methods currently available.

PMID- 23553642
TI  - Synthesis, DNA-binding, cytotoxicity, photo cleavage, antimicrobial and docking
      studies of Ru(II) polypyridyl complexes.
AB  - Three Ruthenium(II) polypyridine complexes, [Ru(phen)2(mipc)](2+)(1),
      [Ru(bpy)2(mipc)](2+) (2) and [Ru(dmb)2(mipc)](2+)(3) [mipc = 2-(6-methyl-3-(1H
      imidazo[4, 5-f][1,10]-phenanthroline-2-yl)-4H-chromene-4-one, phen = 1,10
      phenanthroline,bpy = 2, 2'bipyridine,dmb = 4, 4'-dimethyl-2, 2'-bipyridine] have
      been synthesized and characterized by elemental analysis, IR, UV-Vis, (1)H& (13)C
      NMR and mass spectra. The DNA-binding properties of the Ruthenium(II) complexes
      were investigated by spectrophotometric methods, viscosity measurements and light
      switch studies. These three complexes have been focused on photo activated
      cleavage studies with pBR-322 and antimicrobial studies. Experimental results
      indicate that the three complexes intercalate into DNA base pairs and follows the
      order of 1 > 2 > 3 respectively. Molecular docking studies also support the DNA
      interactions with complexes through hydrogen bonding and vander Waal's
      interactions. Cytotoxicity studies with Hela cell lines has been revealing about
      anti tumor activity of these complexes.

PMID- 23553643
TI  - Hepatitis C virus treatment for prevention among people who inject drugs:
      Modeling treatment scale-up in the age of direct-acting antivirals.
AB  - Substantial reductions in hepatitis C virus (HCV) prevalence among people who
      inject drugs (PWID) cannot be achieved by harm reduction interventions such as
      needle exchange and opiate substitution therapy (OST) alone. Current HCV
      treatment is arduous and uptake is low, but new highly effective and tolerable
      interferon-free direct-acting antiviral (DAA) treatments could facilitate
      increased uptake. We projected the potential impact of DAA treatments on PWID HCV
      prevalence in three settings. A dynamic HCV transmission model was parameterized
      to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne,
      Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future
      DAAs (90% sustained viral response, 12 weeks duration, available 2015), we
      projected the treatment rates required to reduce chronic HCV prevalence by half
      or three-quarters within 15 years. Current HCV treatment rates may have a minimal
      impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but
      could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve
      within 15 years with treatment scale-up to 15, 40, or 76 per 1,000 PWID annually
      in Edinburgh, Melbourne, or Vancouver, respectively (2-, 13-, and 15-fold
      increases, respectively). Scale-up to 22, 54, or 98 per 1,000 PWID annually could
      reduce prevalence by three-quarters within 15 years. Less impact occurs with
      delayed scale-up, higher baseline prevalence, or shorter average injecting
      duration. Results are insensitive to risk heterogeneity or restricting treatment
      to PWID on OST. At existing HCV drug costs, halving chronic prevalence would
      require annual treatment budgets of US $3.2 million in Edinburgh and
      approximately $50 million in Melbourne and Vancouver. CONCLUSION: Interferon-free
      DAAs could enable increased HCV treatment uptake among PWID, which could have a
      major preventative impact. However, treatment costs may limit scale-up, and
      should be addressed.

PMID- 23553645
TI  - Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition
      in human thyroid carcinoma cell lines.
AB  - Well-differentiated papillary and follicular thyroid carcinoma are the most
      frequent types of thyroid cancer and the prognosis is generally favorable
      however, a number of patients develops recurrences. Epigallocatechin-3-gallate
      (EGCG), a major catechin in green tea, was shown to possess remarkable
      therapeutic potential against various types of human cancers, although data on
      thyroid cancer cells are still lacking. The aim of this study was to investigate
      the effect of EGCG on the proliferation and motility of human thyroid papillary
      (FB-2) and follicular (WRO) carcinoma cell lines. Our results demonstrate that
      EGCG (10, 40, 60 MUM) treatment inhibited the growth of FB-2 and WRO cells in a
      dose-dependent manner. These changes were associated with reduced cyclin D1,
      increased p21 and p53 expression. Furthermore, EGCG suppressed phosphorylation of
      AKT and ERK1/2. In addition EGCG treatment results in reduction of cell motility
      and migration. Changes in motility and migration in FB-2 were associated with
      modulation in the expression of several proteins involved in cell adhesion and
      reorganization of actin cytoskeleton. After 24 h EGCG caused an increase of the E
      cadherin expression and a concomitant decrease of SNAIL, ZEB and the basic helix
      loop-helix transcription factor TWIST. Besides expression of Vimentin, N-cadherin
      and alpha5-integrin was down-regulated. These data well correlate with a
      reduction of MMP9 activity as evidenced by gelatin zymography. Our findings
      support the inhibitory role of EGCG on thyroid cancer cell proliferation and
      motility with concomitant loss of epithelial-to-mesenchymal cell transition
      markers.

PMID- 23553646
TI  - An anthropological genetic perspective on Creolization in the Anglophone
      Caribbean.
AB  - Variable socio-cultural influences developed in the colonial Caribbean as a
      result of competing European hegemonic rule. In this study, we examine how
      colonial regulations regarding social hierarchies and mate choice worked to
      influence the genetic landscape of contemporary African Caribbean populations. To
      this end, 420 individuals from Dominica, Grenada, St. Kitts, St. Lucia, St.
      Thomas, St. Vincent, Jamaica, and Trinidad were genotyped for 105 autosomal
      ancestry informative markers. Based on these data, population substructure and
      admixture were assessed using an exact test, a model-based clustering method, and
      principal components analysis. On average, individual admixture estimates of the
      pooled African Caribbean sample were 77% (SD +/- 18%) West African, 15% (SD +/-
      15%) European, and 7.7% (SD +/- 8%) Native American. In general, ancestry
      estimates were significantly different between Dominica and all other islands.
      Genetic structure analyses indicated subdivision into two subpopulations on most
      islands. Finally, unlike all of the other Caribbean populations that clustered
      adjacent to African populations, the Dominican population was more intermediate
      between the three parental groups in the principal components plot. As a result
      of the significant French influence throughout Dominican history, Dominica did
      not have the same cultural influences that typified other Anglophone colonies.
      Consequently, there were different social hierarchies and resulting mate choices
      on Dominica compared with the other considered islands. This study highlights the
      complex socio-cultural history of a broad region of the Caribbean and attests to
      the interplay between social and biological factors in shaping the genetic
      diversity present in present-day communities.

PMID- 23553647
TI  - Synthesis, characterization, and reactivity of dyad ruthenium-based molecules for
      light-driven oxidation catalysis.
AB  - Dyad molecules containing the 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tppz) ligand
      with general formula [(tpy)Ru(MU-tppz)Ru(X)(L-L)](n+) (X=Cl, CF3COO, or H2O; L
      L=2,2'-bipyridine (bpy) or 3,5-bis(2-pyridyl)pyrazole (Hbpp); tpy=2,2':6',2"
      terpyridine) have been prepared, purified, and isolated. The complexes have been
      characterized by analytical and spectroscopic techniques and by X-ray diffraction
      analysis for two of them. Additionally, full electrochemical characterization
      based on cyclic voltammetry, differential pulse voltammetry, and square wave
      voltammetry has been also performed. The pH dependence of the redox couples for
      the aqua complexes have also been studied and their corresponding Pourbaix
      diagrams drawn. Furthermore, their capacity to catalytically oxidize organic
      substrates, such as alcohols, alkenes, and sulfides, has been carried out
      chemically, electrochemically, and photochemically. Finally, their capacity to
      behave as water oxidation catalysts has also been tested.

PMID- 23553648
TI  - Chemical characteristics and biofuels potentials of various plant biomasses:
      influence of the harvesting date.
AB  - BACKGROUND: An optimal valorization of plant biomasses to produce biofuels
      requires a good knowledge of the available contents and molecular composition of
      the main chemical components, which changes with the harvesting date. Therefore,
      we assessed the influence of harvesting date on the chemical characteristics of
      various energy crops in the context of their conversion to biofuels. RESULTS: We
      showed that the biomass chemical composition, enzymatic digestible organic
      matter, bioethanol and thermal energy production potential for each species are
      impacted by the harvesting date. The proportion of enzymatically digestible
      organic matter decreases as the harvesting date is delayed. This is related to
      the increase in cellulose and lignin contents. The suitability of the biomasses
      for bioethanol production increases with harvest stage, as the total
      carbohydrates content increases. The suitability of the biomasses as a source of
      thermal energy increases according to the harvesting date as the proportion of
      organic matter increases and the content of mineral compounds decreases. For all
      investigated energy conversions, the best harvesting period is autumn, because
      the significantly higher crop dry matter yield largely compensates for the
      sometimes slightly less favorable chemical characteristics. CONCLUSION: While the
      biomass composition of energy crops changes with harvest stage, the dry biomass
      yield per unit area is the main factor that controls the total amount of chemical
      components, digestible organic matter, bioethanol and thermal energy that can be
      expected to be harvested per unit area. The biomass compositions presented in
      this paper are essential to investigate their suitability for bioenergy
      conversion.

PMID- 23553649
TI  - Motivating health workers for the provision of directly observed treatment to TB
      patients in rural China: does cash incentive work? A qualitative study.
AB  - As a key component of DOTS (directly observed treatment, short course) strategy,
      DOT is essential in the prevention of drug-resistant tuberculosis. However, DOT
      had very poor implementation in rural areas of China. One major reason to this
      problem was the lack of incentives for DOT providers. In 2005, the Chinese
      Minister of Health released an incentive strategy that aimed to improve the DOT
      performance of rural health workers by providing allowances. Our study used a
      qualitative method to explore the practical impact of this incentive strategy in
      motivating rural DOT providers, and searched for other potential incentive
      measures as well. A total of 16 focus group discussions were carried out among
      102 rural health workers in eight counties of China. A semi-structured theme
      outline was used to collect the perception, attitude and experiences of health
      workers toward the DOT implementation as well as the cash incentive strategy.
      Findings showed that DOT allowance had some incentive effect to DOT providers,
      but its extent was circumscribed by the small amount and operational problems.
      Raising DOT allowance and removing existing barriers to DOT provision might
      result in a greater motivational impact, particularly in less developed areas of
      China, where health workers were more likely to encounter financial and other
      obstacles in delivering DOT services to TB patients in rural areas.

PMID- 23553650
TI  - Chirality and chiroptical effects in plasmonic nanostructures: fundamentals,
      recent progress, and outlook.
AB  - Strong chiroptical effects recently reported result from the interaction of light
      with chiral plasmonic nanostructures. Such nanostructures can be used to enhance
      the chiroptical response of chiral molecules and could also significantly
      increase the enantiomeric excess of direct asymmetric synthesis and catalysis.
      Moreover, in optical metamaterials, chirality leads to negative refractive index
      and all the promising applications thereof. In this Progress Report, we highlight
      four different strategies which have been used to achieve giant chiroptical
      effects in chiral nanostructures. These strategies consecutively highlight the
      importance of chirality in the nanostructures (for linear and nonlinear
      chiroptical effects), in the experimental setup and in the light itself. Because,
      in the future, manipulating chirality will play an important role, we present two
      examples of chiral switches. Whereas in the first one, switching the chirality of
      incoming light causes a reversal of the handedness in the nanostructures, in the
      second one, switching the handedness of the nanostructures causes a reversal in
      the chirality of outgoing light.

PMID- 23553651
TI  - Evaluation of hydroxylamine oxidoreductase as a functional and phylogenetic
      marker to differentiate Nitrosomonas spp.
AB  - Nitrosomonas genus belongs to beta-subclass of Proteobacteria and encompasses
      closely related species. Sequence independent techniques like single strand
      confirmation polymorphism (SSCP) was attempted in the present study to resolve
      AOB using ammonia monooxygenase (amoA) and hydroxylamine oxidoreductase (hao)
      gene fragments, unique to AOB. Variation in hydroxylamine oxidoreductase (HAO)
      enzyme zymogram of isolates observed in the study was also explored as an
      additional sequence independent method to substantiate the observations.
      Nitrosomonas europaea (standard strain) and 12 isolates, obtained by enriching
      environmental samples, were differentiated into six and four groups by SSCP
      analyses of amoA and hao gene fragments, respectively, whereas they could be
      resolved into six distinct groups through activity staining of HAO enzyme. amoA
      gene fragment was therefore found to be better than hao gene fragment in
      resolving the studied AOB based on richness and evenness with Simpson's index of
      diversity - 0.85. However, the ensembled use of these molecular methods (SSCP of
      amoA and hao gene fragments) and HAO enzyme zymogram in fingerprinting AOB
      provide better resolution and evenness, contributing significantly in AOB
      diversity studies. Grouping of AOB isolates by hao gene SSCP analysis followed
      almost the same pattern as that by 16S rRNA gene based sequence analysis, hence
      it is suitable as a phylogenetic marker. 

PMID- 23553652
TI  - Obstructive sleep apnea increases the risk of bladder pain syndrome/interstitial
      cystitis: a population-based matched-cohort study.
AB  - AIMS: Previous studies indicated a possible association between bladder pain
      syndrome/interstitial cystitis (BPS/IC) and sleep disorders including sleep
      abnormalities with delayed onset of sleep, waking up before needed, and snoring.
      Nevertheless, no previous study has reported the association between obstructive
      sleep apnea (OSA) and BPS/IC. In this retrospective cohort study, we examined the
      risk of BPS/IC among subjects with OSA during a 3-year follow-up in Taiwan using
      a population-based dataset. METHODS: This study comprised 2,940 study subjects
      with OSA, and 29,400 randomly selected comparison subjects. We individually
      followed-up each sampled subject (n = 32,340) for a 3-year period to identify
      those subjects who subsequently received a diagnosis of BPS/IC. A Cox
      proportional hazards regression model was constructed to estimate the risk of
      subsequent BPS/IC following a diagnosis of OSA. RESULTS: Incidences of BPS/IC
      during the 3-year follow-up period were 13.61 (95% confidence interval [CI] =
      7.37-23.13) and 3.60 (95% CI = 2.06-4.39) for subjects with and those without
      OSA, respectively. After adjusting for diabetes, hypertension, coronary heart
      disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome,
      fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines,
      sicca syndrome, allergies, endometriosis, asthma, tobacco use disorder, and
      alcohol abuse, the stratified Cox proportional hazards regressions revealed that
      the hazard ratio for BPS/IC among subjects with OSA was 3.71 (95% CI = 1.81-7.62,
      P < 0.001) that of comparison subjects. CONCLUSIONS: This study provides
      epidemiological evidence of a link between OSA and a subsequent BPS/IC diagnosis.
      We suggest that clinical practitioners treating subjects with OSA be alert to
      urinary complaints in this population.

PMID- 23553653
TI  - A new paradigm for the management of essential vocal tremor with botulinum toxin.
AB  - OBJECTIVES/HYPOTHESIS: 1) To clarify essential voice tremor (EVT) phenomenology;
      2) To report a management paradigm for essential voice tremor using botulinum
      toxin. STUDY DESIGN: Retrospective analysis of prospectively collected data.
      METHODS: Phenomenology from patients diagnosed with EVT between April 1996 and
      March 2012 was recorded, charted, and analyzed. A paradigm for treatment of EVT
      using botulinum toxin based on individualized clinical findings is discussed.
      RESULTS: Sixteen patients were included. Fewer than 50% patients were responsive
      to centrally acting oral medications. Fifteen patients analyzed had horizontal
      laryngeal tremor and received botulinum toxin injections to bilateral
      thyroarytenoid muscles. Thirteen patients had a vertical laryngeal tremor, and
      these patients underwent additional strap muscle injections. All patients had
      symptomatic improvement with reduced tremor amplitude. Dose adjustments over time
      depended on degree of symptomatic improvement. CONCLUSIONS: Management of
      essential voice tremor with botulinum toxin is optimized by individualizing
      treatment based on the tremor phenomenology observed during clinical examination.
      LEVEL OF EVIDENCE: 4.

PMID- 23553654
TI  - Trisomies 18 and 13: trends in prevalence and prenatal diagnosis - population
      based study.
AB  - OBJECTIVE: The objective of this study was to determine trends in prenatal
      detection and current estimates of prevalence for trisomies 18 (T18) and 13 (T13)
      and their implications for screening policy. METHODS: We conducted a cohort study
      from a population-based regional anomaly register covering 995 003 births (1995
      2009). RESULTS: There were 786 affected cases. Total prevalence of T18 increased
      from 3.95 in 1995-1999 to 6.94 per 10 000 births in 2005-2009 (annual trend
      chi(2)  = 25.99, p < 0.001) and live birth prevalence, when adjusted for in utero
      attrition, increased from 1.47 to 2.30 per 10 000 births over the same time
      (annual trend chi(2)  = 6.36, p = 0.01). For T18 and T13 combined, the proportion
      of cases diagnosed by prenatal karyotype or suspected by ultrasound increased
      from 85.1% (165/194) in 1995-1999 to 95.2% (299/314) in 2005-2009 (p < 0.001). In
      2005-2009, 50.3% of prenatal cytogenetic diagnoses for T18 and 38.5% of T13 were
      made after the discovery of first trimester ultrasound anomalies, and the
      majority, 56.4% (185/328), of affected pregnancies were karyotyped or had ended
      before 18 weeks. CONCLUSION: T18 is increasing in prevalence because of maternal
      age and earlier surveillance. Prenatal diagnosis occurs mostly in the first
      trimester, without the intrinsic structures of a formal screening programme.
      These findings support the extension of first trimester combined screening to
      include T18 and T13.

PMID- 23553655
TI  - Treatment-, patient-, and disease-related factors and the emergence of adverse
      events with tyrosine kinase inhibitors for the treatment of chronic myeloid
      leukemia.
AB  - Four breakpoint cluster region (BCR)-ABL1 tyrosine kinase inhibitors (TKIs) are
      currently available for the treatment of chronic myeloid leukemia (CML):
      imatinib, nilotinib, dasatinib, and bosutinib. Choosing the most appropriate TKI
      requires clinicians to consider a host of patient-, disease-, and treatment
      related factors, not the least of which include the safety profiles of the
      agents. This review discusses the potential impact of treatment-, patient-, and
      disease-related characteristics on the emergence of adverse events during TKI
      therapy, with a focus on the underlying mechanisms believed to be responsible for
      a number of important adverse events associated with these agents and what
      implications they may have for treatment choice, particularly in the setting of
      first-line treatment. A literature search of the PubMed database was conducted to
      identify articles that described the molecular mechanisms of BCR-ABL1-mediated
      leukemic transformation, the efficacy and safety of imatinib, nilotinib,
      dasatinib, and bosutinib in patients with CML, the kinase-binding spectrum of
      each TKI, and evidence suggesting a link between the TKI-binding profile and
      adverse events. The pattern of adverse events associated with each agent is
      important when selecting treatment with a TKI. Clinical studies suggest that
      imatinib, nilotinib, dasatinib, and bosutinib have differing safety profiles,
      which are in part attributable to the specificity and selectivity of each agent.
      Although much basic research must be conducted to further illuminate the
      mechanisms responsible for TKI-related adverse events, on- and off-target effects
      are believed to be at least partly responsible for cardiovascular toxicity,
      myelosuppression, fluid retention, gastrointestinal toxicity, and dermatologic
      toxicity. Increased understanding of the factors that affect TKI-associated
      adverse events and long-term safety data will enable a more informed approach to
      the selection of therapy best suited to the individual needs of patients with
      CML. 

PMID- 23553656
TI  - Interlayer penetration depth in the pseudogap phase of cuprate superconductors.
AB  - The opening of a pseudogap in the electronic structure of the underdoped high Tc
      cuprates has a profound effect on superconducting properties. Here we consider
      the c-axis penetration depth. A phenomenological model of the pseudogap due to
      Yang, Rice, and Zhang (YRZ) is used. It is based on the idea of a resonating
      valence bond spin liquid. A simplifying limit, the arc model, is also considered
      as it provides useful analytic formulas. The zero temperature value of the
      superfluid density n(s)(T = 0) is greatly reduced with increasing values of the
      pseudogap (Deltapg). This value reflects the reconstruction of the Fermi surface
      from the large contour of Fermi liquid theory to ever smaller Luttinger pockets
      as Deltapg becomes larger. Also, as temperature is increased the ratio
      n(s)(T)/n(s)(0) as a function of the reduced temperature t = T/T(c) decreases
      more rapidly than in the corresponding Fermi liquid (Deltapg = 0) as states which
      have both superconducting and pseudogap become more significantly sampled.

PMID- 23553657
TI  - Identifying locations for public access defibrillators using mathematical
      optimization.
AB  - BACKGROUND: Geospatial methods using mathematical optimization to identify
      clusters of cardiac arrests and prioritize public locations for defibrillator
      deployment have not been studied. Our objective was to develop such a method and
      test its performance against a population-guided approach. METHODS AND RESULTS:
      All public location cardiac arrests in Toronto, Ontario, Canada, from December
      16, 2005, to July 15, 2010, and all automated external defibrillator (AED)
      locations registered with Toronto Emergency Medical Services as of September 2009
      were plotted geographically. Current AED coverage was quantified by determining
      the number of cardiac arrests occurring within 100 m of a registered AED.
      Clusters of cardiac arrests without a registered AED within 100 m were
      identified. With the use of mathematical optimization techniques, cardiac arrest
      coverage improvements were computed and shown to be superior to results from a
      population-guided deployment method. There were 1310 eligible public location
      cardiac arrests and 1669 registered AEDs. Of the eligible cardiac arrests, 304
      were within 100 m of at least 1 registered AED (23% coverage). The average
      distance from a cardiac arrest to the closest AED was 281 m. With AEDs deployed
      in the top 30 locations, an additional 112 historical cardiac arrests would be
      covered (32% total coverage), and the average distance to the closest AED would
      be 262 m. CONCLUSIONS: Geographic clusters of cardiac arrests can be easily
      identified and prioritized with the use of mathematical modeling. Optimized AED
      deployment can increase cardiac arrest coverage and decrease the distance to the
      closest AED. Mathematical modeling can augment public AED deployment programs.

PMID- 23553658
TI  - SOCS-1/3 participation in FGF-2 signaling to modulate RANK ligand expression in
      paget's disease of bone.
AB  - Paget's disease of bone (PDB) is a chronic focal skeletal disorder characterized
      by excessive bone resorption followed by disorganized new bone formation. Measles
      virus nucleocapsid (MVNP) is implicated in pathogenesis of PDB. RANK ligand
      (RANKL), a critical osteoclastogenic factor expressed on bone marrow
      stromal/preosteoblast cells is upregulated in PDB. We recently demonstrated that
      fibroblast growth factor-2 (FGF-2) which induces RANKL expression is elevated in
      PDB. In this study, we hypothesized that FGF-2 modulates suppressors of cytokine
      signaling (SOCS) to induce RANKL expression in PDB. We identified increased
      levels of SOCS-1/3 mRNA expression in bone marrow mononuclear cells derived from
      patients with PDB compared to normal subjects. Interestingly, conditioned media
      obtained from MVNP transduced osteoclast progenitor cells significantly increased
      SOCS-1/3 mRNA expression in stromal/preosteoblast cells. We next examined if SOCS
      participates in FGF-2 signaling to modulate RANKL gene expression. We showed that
      FGF-2 stimulation significantly increased SOCS-1/3 expression in human bone
      marrow stromal/preosteoblast cells. In addition, co-expression of SOCS-1/3 with
      hRANKL gene promoter-luciferase reporter plasmid in marrow stromal cells
      demonstrated a significant increase in promoter activity without FGF-2
      stimulation. Furthermore, siRNA inhibition of STAT-1 suppresses FGF-2 increased
      SOCS-1/3 expression in these cells. Thus, our results suggest that SOCS
      participates in FGF-2 modulation of RANKL expression in PDB.

PMID- 23553660
TI  - Successful treatment of skin fistulas in systemic sclerosis patients with the
      combination of topical negative pressure therapy and split-thickness skin
      grafting.

PMID- 23553663
TI  - Into the wild--the use and abuse of stem cells in clinical practice.

PMID- 23553664
TI  - Tako-tsubo cardiomyopathy following modafinil use.

PMID- 23553665
TI  - Relationship between nicotine dependence and the endophenotype-related trait of
      cognitive function but not acoustic startle reponses in Japanese patients with
      schizophrenia.
AB  - OBJECTIVES: We investigated whether nicotine dependence affects these
      endophenotypes in Japanese schizophrenia patients and whether alpha4 and beta2
      subunits of neuronal nicotinic acetylcholine receptor genes (alpha4 subunit of
      the nAChR gene (CHRNA4)/beta2 subunit of the nAChR gene (CHRNB2)) were associated
      with nicotine dependence in patients (n = 100) and healthy controls (n = 107).
      METHODS: First, in patients, we evaluated cognitive function, using the Brief
      Assessment of Cognition in Schizophrenia, and acoustic startle responses. Second,
      we evaluated the severity of nicotine dependence, using the Tobacco Dependence
      Screener, the Fagerstrom Test for Nicotine Dependence, and the Brinkman index in
      current smokers in both groups. Third, we evaluated the relationship between
      acoustic startle responses, cognitive function, and severity of nicotine
      dependence. Finally, using 12 tagging single-nucleotide polymorphisms in each the
      CHRNA4/CHRNB2, we used multiple linear regression analysis to examine the
      association between nicotine dependence measures and each selected single
      nucleotide polymorphism. RESULTS: The presence and severity of nicotine
      dependence were associated with verbal memory and executive function in
      schizophrenia patients. However, nicotine dependence was not correlated with any
      acoustic startle response. In addition, rs755203 and rs1044397 in CHRNA4 were
      associated with nicotine dependence in healthy controls. CONCLUSIONS: Nicotine
      dependence might influence the level of verbal memory and executive function in
      schizophrenia patients. In addition, rs755203 and rs1044397 in CHRNA4 might play
      a role in the pathophysiology of nicotine dependence in healthy controls in the
      Japanese population.

PMID- 23553666
TI  - Vitamin D-binding protein gene polymorphisms may contribute to the racial
      disparity in genotype 1 chronic hepatitis C treatment outcome.

PMID- 23553667
TI  - Sh3tc2 deficiency affects neuregulin-1/ErbB signaling.
AB  - Mutations in SH3TC2 trigger autosomal recessive demyelinating Charcot-Marie-Tooth
      type 4C (CMT4C) neuropathy. Sh3tc2 is specifically expressed in Schwann cells and
      is necessary for proper myelination of peripheral axons. In line with the early
      onset of neuropathy observed in patients with CMT4C, our analyses of the murine
      model of CMT4C revealed that the myelinating properties of Sh3tc2-deficient
      Schwann cells are affected at an early stage. This early phenotype is associated
      with changes in the canonical Nrg1/ErbB pathway involved in control of
      myelination. We demonstrated that Sh3tc2 interacts with ErbB2 and plays a role in
      the regulation of ErbB2 intracellular trafficking from the plasma membrane upon
      Nrg1 activation. Interestingly, both the loss of Sh3tc2 function in mice and the
      pathological mutations present in CMT4C patients affect ErbB2 internalization,
      potentially altering its downstream intracellular signaling pathways. Altogether,
      our results indicate that the molecular mechanism for the axonal size sensing is
      disturbed in Sh3tc2-deficient myelinating Schwann cells, thus providing a novel
      insight into the pathophysiology of CMT4C neuropathy.

PMID- 23553668
TI  - Genetic counseling training in the Philippines.
AB  - The recently established Master of Science in Genetic Counseling (MSGC) program
      serves a vital role in implementing and expanding genetic counseling services in
      the Philippines. Currently, only eight clinical geneticists practice in the
      Philippines, a country of approximately 94 million people, which yields a
      clinical-geneticist-to-population-density ratio of 1:11,750,000. The MSGC program
      was created to train health care providers to become crucial members of medical
      genetics teams being formed to meet increasing patient and healthcare provider
      demands. In 2011, the Board of Regents approved our proposed curriculum at the
      Department of Pediatrics College of Medicine, University of the Philippines
      Manila. As we relate how the Philippines began its efforts to implement the
      program and attempted to overcome the challenges the program faced, we hope we
      can provide an example to those interested in creating a similar MSGC program in
      other low-income and middle-income countries. 

PMID- 23553669
TI  - Mediterranean diet and health.
AB  - Over the last decades, a considerable body of evidence supported the hypothesis
      that diet and dietary factors play a relevant role in the occurrence of diseases.
      To date, all the major scientific associations as well as the World Health
      Organization and the nonscientific organizations place an ever-increasing
      emphasis on the role of diet in preventing noncommunicable diseases. Many studies
      have evaluated the associations between food groups, foods, or nutrients and
      chronic diseases, and a consensus about the role of nutritional factors in the
      etiology of common diseases, such as cardiovascular and neoplastic diseases, has
      gradually emerged. Indeed, data from analytical and experimental studies
      indicated a relation between increased consumption of some food categories such
      as fruits and vegetables, fiber and whole grains, fish, and moderate consumption
      of alcohol and reduced risk of major chronic degenerative diseases, whereas
      increased total caloric intake, body weight, meat, and fats are associated with
      greater risk. However, the appropriate dietary strategy to prevent chronic
      degenerative diseases remains a challenging and a highly relevant issue.
      Recently, Mediterranean diet has been extensively reported to be associated with
      a favorable health outcome and a better quality of life. In the present review,
      we encompass the updated evidence of the beneficial effects of Mediterranean diet
      in the occurrence of major chronic degenerative diseases.

PMID- 23553670
TI  - Unimolecular reaction mechanism of an imidazolin-2-ylidene: an iPEPICO study on
      the complex dissociation of an Arduengo-type carbene.
AB  - The photoionization and dissociative photoionization of Im(iPr)2, 1,3
      diisopropylimidazolin-2-ylidene, was investigated by imaging photoelectron
      photoion coincidence (iPEPICO) with vacuum ultraviolet (VUV) synchrotron
      radiation. A lone-pair electron of the carbene carbon atom is removed upon
      ionization and the molecular geometry changes significantly. Only 0.5 eV above
      the adiabatic ionization energy, IEad =7.52+/-0.1 eV, the carbene cation
      fragments, yielding propene or a methyl radical in parallel dissociation
      reactions with appearance energies of 8.22 and 8.17 eV, respectively. Both
      reaction channels appear at almost the same photon energy, suggesting a shared
      transition state. This is confirmed by calculations, which reveal the rate
      determining step as hydrogen-atom migration from the isopropyl group to the
      carbene carbon center forming a resonance-stabilized imidazolium ion. Above 10.5
      eV, analogous sequential dissociation channels open up. The first propene-loss
      fragment ion dissociates further and another methyl or propene is abstracted.
      Again, a resonance-stabilized imidazolium ion acts as intermediate. The
      aromaticity of the system is enhanced even in vertical ionization. Indeed, the
      coincidence technique confirms that a real imidazolium ion is produced by
      hydrogen transfer over a small barrier. The simple analysis of the breakdown
      diagram yields all the clues to disentangle the complex dissociative
      photoionization mechanism of this intermediate-sized molecule. Photoelectron
      photoion coincidence is a promising tool to unveil the fragmentation mechanism of
      larger molecules in mass spectrometry.

PMID- 23553672
TI  - Preischemic exercise reduces brain damage by ameliorating metabolic disorder in
      ischemia/reperfusion injury.
AB  - Physical exercise preconditioning is known to ameliorate stroke-induced injury.
      In addition to several other mechanisms, the beneficial effect of preischemic
      exercise following stroke is due to an upregulated capacity to maintain energy
      supplies. Adult male Sprague-Dawley rats were used in exercise and control
      groups. After 1-3 weeks of exercise, several enzymes were analyzed as a gauge of
      the direct effect of physical exercise on cerebral metabolism. As a measure of
      metabolic capacity, an ADP/ATP ratio was obtained. Glucose transporters (GLUT1
      and GLUT3) were monitored to assess glucose influx, and phosphofructokinase (PFK)
      was measured to determine the rate of glycolysis. Hypoxia-induced factor-1alpha
      (HIF-1alpha) and 5'AMP-activated protein kinase (AMPK) levels were also
      determined. These same analyses were performed on preconditioned and control rats
      following an ischemic/reperfusion (I/R) insult. Our results show that GLUT1,
      GLUT3, PFK, AMPK, and HIF-1alpha were all increased following 3 weeks of exercise
      training. In addition, the ADP/ATP ratio was chronically elevated during these 3
      weeks. After I/R injury, HIF-1alpha and AMPK were significantly higher in
      exercised rats. The ADP/ATP ratio was reduced in preconditioned rats in the acute
      phase after stroke, suggesting a lower level of metabolic disorder. GLUT1 and
      GLUT3 were also increased in the acute phase in exercise rats, indicating that
      these rats were better able to increase rates of metabolism immediately after
      ischemic injury. In addition, PFK expression was increased in exercise rats
      showing an enhanced glycolysis resulting from exercise preconditioning.
      Altogether, exercise preconditioning increased the rates of glucose metabolism,
      allowing a more rapid and more substantial increase in ATP production following
      stroke.

PMID- 23553673
TI  - Water recycle as a must: decolorization of textile wastewaters by plant
      associated fungi.
AB  - Textile dye effluents are among the most problematic pollutants because of their
      toxicity on several organisms and ecosystems. Low cost and ecocompatible
      bioremediation processes offer a promising alternative to the conventional and
      aspecific physico-chemical procedures adopted so far. Here, microorganisms
      resident on three real textile dyeing effluent were isolated, characterized, and
      tested for their decolorizing performances. Although able to survive on these
      real textile-dyeing wastewaters, they always showed a very low decolorizing
      activity. On the contrary, several plant-associated fungi (Bjerkandera adusta,
      Funalia trogii, Irpex lacteus, Pleurotus ostreatus, Trametes hirsuta, Trichoderma
      viride, and Aspergillus nidulans) were also assayed and demonstrated to be able
      both to survive and to decolorize to various extents the three effluents, used as
      such in liquid cultures. The decolorizing potential of these fungi was
      demonstrated to be influenced by nutrient availability and pH. Best performances
      were constantly obtained using B. adusta and A. nidulans, relying on two strongly
      different mechanisms for their decolorizing activities: degradation for B. adusta
      and biosorption for A. nidulans. Acute toxicity tests using Daphnia magna showed
      a substantial reduction in toxicity of the three textile dyeing effluents when
      treated with B. adusta and A. nidulans, as suggested by mass spectrometric
      analysis as well. 

PMID- 23553675
TI  - Describing the primary care system capacity for the prevention and management of
      non-communicable diseases in rural Vietnam.
AB  - BACKGROUND: The primary care system in Vietnam has been shown to play a crucial
      role in disease prevention and health promotion. This study described the primary
      care system in a selected rural area in Vietnam in terms of its capacity for
      prevention and control of non-communicable diseases (NCDs). METHODS: The study
      was conducted in 2011 in Dong Hy district, Thai Nguyen province-a rural community
      located in northern Vietnam. Mixed methods were used, including quantitative and
      qualitative and literature review approaches, to collect data on the current
      status of the six building blocks of the primary care system in Dong Hy district.
      Selected health workers and stakeholders in the selected healthcare facilities
      were surveyed. RESULTS: A description of Dong Hy district's primary care capacity
      for NCD prevention and control is reported. (i) Service delivery: The current
      practice in NCD prevention and treatment is mainly based on a single risk factor
      rather than a combination of cardiovascular disease risks. (ii) Governance: At
      the primary care level, multi-sectoral collaborations are limited, and there is
      insufficient integration of NCD preventive activities. (iii) Financing: A
      national budget for NCD prevention and control is lacking. The cost of treatment
      and medicines is high, whereas the health insurance scheme limits the list of
      available medicines and the reimbursement ceiling level. Health workers have low
      remuneration despite their important roles in NCD prevention. (iv) Human
      resources: The quantity and quality of health staff working at the primary care
      level, especially those in preventive medicine, are insufficient. (v) Information
      and research: The health information system in the district is weak, and there is
      no specific information system for collecting population-based NCD data. (vi)
      Medical products and technology: Not all essential equipment and medicines
      recommended by the WHO are always available at the commune health centre.
      CONCLUSION: The capacity of the primary care system in Vietnam is still
      inadequate to serve the NCD-related health needs of the population. There is an
      urgent need to improve the primary care capacity for NCD prevention and
      management in Vietnam.

PMID- 23553671
TI  - Gene and cell-mediated therapies for muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a devastating muscle disorder that affects 1
      in 3,500 boys. Despite years of research and considerable progress in
      understanding the molecular mechanism of the disease and advancement of
      therapeutic approaches, there is no cure for DMD. The current treatment options
      are limited to physiotherapy and corticosteroids, and although they provide a
      substantial improvement in affected children, they only slow the course of the
      disorder. On a more optimistic note, more recent approaches either significantly
      alleviate or eliminate muscular dystrophy in murine and canine models of DMD and
      importantly, many of them are being tested in early phase human clinical trials.
      This review summarizes advancements that have been made in viral and nonviral
      gene therapy as well as stem cell therapy for DMD with a focus on the replacement
      and repair of the affected dystrophin gene.

PMID- 23553676
TI  - Shape and volume of craniofacial cavities in intentional skull deformations.
AB  - Intentional cranial deformations (ICD) have been observed worldwide but are
      especially prevalent in preColombian cultures. The purpose of this study was to
      assess the consequences of ICD on three cranial cavities (intracranial cavity,
      orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen
      for morphological changes due to the external constraints exerted by the
      deformation device. We acquired CT-scans for 39 deformed and 19 control skulls.
      We studied the thickness of the skull vault using qualitative and quantitative
      methods. We computed the volumes of the orbits, of the maxillary sinuses, and of
      the intracranial cavity using haptic-aided semi-automatic segmentation. We
      finally defined 3D distances and angles within orbits and maxillary sinuses based
      on 27 anatomical landmarks and measured these features on the 58 skulls. Our
      results show specific bone thickness patterns in some types of ICD, with
      localized thinning in regions subjected to increased pressure and thickening in
      other regions. Our findings confirm that volumes of the cranial cavities are not
      affected by ICDs but that the shapes of the orbits and of the maxillary sinuses
      are modified in circumferential deformations. We conclude that ICDs can modify
      the shape of the cranial cavities and the thickness of their walls but conserve
      their volumes. These results provide new insights into the morphological effects
      associated with ICDs and call for similar investigations in subjects with
      deformational plagiocephalies and craniosynostoses.

PMID- 23553677
TI  - A localized surface plasmon resonance-based multicolor electrochromic device with
      electrochemically size-controlled silver nanoparticles.
AB  - The first localized surface plasmon resonance (LSPR)-based multicolor
      electrochromic device with five reversible optical states is demonstrated. In
      this device, the size of deposited silver nanoparticles is electrochemically
      controlled by using a voltage-step method in which two different voltages are
      applied successively. The electrochemically size-controlled silver nanoparticles
      enable a reversible multiple-color change by a shift of the LSPR band.

PMID- 23553674
TI  - Reversal of cardiac dysfunction and subcellular alterations by metoprolol in
      heart failure due to myocardial infarction.
AB  - In order to examine the reversibility of heart failure due to myocardial
      infarction (MI) by beta-adrenoceptor blockade, 12 weeks infarcted rats were
      treated with or without metoprolol (50 mg/kg/day) for 8 weeks. The depressed left
      ventricular (LV) systolic pressure, positive and negative rates of changes in
      pressure development, ejection fraction, fractional shortening and cardiac
      output, as well as increased LV end-diastolic pressure in 20 weeks MI animals
      were partially reversed by metoprolol. MI-induced decreases in septum (systolic)
      thickness as well as increase in LV posterior wall thickness and LV internal
      diameter were partially or fully reversible by metoprolol. Treatment of MI
      animals with metoprolol partially reversed the elevated levels of plasma
      norepinephrine and dopamine without affecting the elevated levels of epinephrine.
      Although sarcoplasmic reticular (SR) Ca(2+)-uptake, as well as protein content
      for SR Ca(2+)-pump and phospholamban, were reduced in the infarcted hearts; these
      changes were partially reversible with metoprolol. Depressed myofibrillar Ca(2+)
      stimulated ATPase activity, as well as mRNA levels for SR Ca(2+)-pump,
      phospholamban and alpha-myosin heavy chain, were unaffected whereas increased
      mRNA level for beta-myosin heavy chain was partially reversed by metoprolol. The
      results suggest that partial improvement of cardiac performance by beta
      adrenoceptor blockade at advanced stages of heart failure may be due to partial
      reversal of changes in SR Ca(2+)-pump function whereas partial to complete
      reverse cardiac remodeling may be due to partial reduction in the elevated levels
      of plasma catecholamines.

PMID- 23553678
TI  - Regional vulnerability of hippocampal subfields and memory deficits in
      Parkinson's disease.
AB  - Neuropathological studies show the hippocampus is affected in Parkinson's disease
      (PD), with the second subfield of the cornu armonis (CA2) being the most
      involved. Our aims were to assess in vivo volumes of different hippocampal
      subfields in patients with PD with and without visual hallucinations using MRI
      and test their association with verbal learning and long-term recall. A total of
      18 nondemented PD patients, 18 nondemented PD patients with visual hallucinations
      and 18 neurologically unimpaired elderly controls matched by age and gender were
      enrolled in this study. We assessed the volumes of seven hippocampal subfields on
      MRI, including the cornu armonis (CA) sectors, subiculum, presubiculum, and the
      dentate gyrus (DG) using a novel technique that enables automated volumetry. The
      CA2-3 and CA4-DG subfields were significantly smaller in both groups of patients,
      while the subiculum was only reduced in PD patients with visual hallucinations,
      compared to controls. Significant correlations were found between learning
      performance and CA2-3 as well as CA4-DG volumes in the whole patient sample.
      These data show there is regional atrophy of specific hippocampal subfields in
      PD, which is more severe and further extends to the subiculum in patients with
      visual hallucinations. Our findings indicate that learning deficits are
      associated with volume loss in subfields that act as input regions in the
      hippocampal circuit, suggesting that degeneration in these regions could be
      responsible for cognitive dysfunction in PD.

PMID- 23553679
TI  - Validation of a novel approach for dose individualization in pharmacotherapy
      using gabapentin in a proof of principles study.
AB  - STUDY OBJECTIVE: To demonstrate the premise of individualized dosing charts
      (IDCs) as a clinical-bedside decision-support tool to individualize dosage
      regimens for drugs in which the interpatient variability is controlled by the
      pharmacokinetic (PK) behavior of the patient, to calculate the optimal sampling
      schedule (OSS), which minimizes the number of blood samples per patient. The
      approach is illustrated with available PK data for gabapentin. DESIGN:
      Retrospective proof of principles study using gabapentin PK data from a published
      clinical trial. PATIENTS: Nineteen subjects in a trial designed to uncover the
      importance of the genetic contributions to variability in gabapentin absorption,
      renal elimination, and transport; subjects were monitored for 36 hours after
      administration of a single dose of gabapentin 400 mg, and plasma concentrations
      were determined at 14 time points. MEASUREMENTS AND MAIN RESULTS: When the PK
      profiles were different between subjects, the IDCs are dramatically different
      from each other and from the IDC for an "average" patient representing the
      patient population. The dose amount and dosing interval must be adjusted to
      maximize the probability of staying within the target concentration range. An
      optimal sampling methodology based on the assumption-free Bayesian approach is
      used to distinguish the PK profile of an individual patient from the patient
      population. In the case of gabapentin, only two optimally selected test blood
      samples, at 1.5 and 6 hours after administration of a single doses, were
      necessary. The average sensitivity and the average specificity of the OSS was 99%
      and 96%, respectively. CONCLUSION: IDCs display the risk of a patient violating
      the target concentration range for any dosage regimen. They can be used as a
      clinical-bedside decision-support tool in a patient-physician partnership to
      decide on a dose amount and dosing interval that are medically acceptable while
      practical and convenient to ensure compliance. By using the assumption-free
      Bayesian approach and the OSS, the number of samples required from a new patient
      to individualize the dosage regimen can be reduced significantly while preserving
      high levels of sensitivity and specificity. Prospective studies are being planned
      to validate the encouraging results. This approach can be extended to any drug if
      PK data and a target concentration range are available for either therapeutic
      drug monitoring or target concentration intervention.

PMID- 23553680
TI  - GLP-1 could improve the similarity of IPCs and pancreatic beta cells in cellular
      ultrastructure and function.
AB  - Transplantation of functional insulin-producing cells (IPCs) provides a novel
      mode for insulin replacement, but is often accompanied by many undesirable side
      effects. Our previous studies suggested that IPCs could not mimic the
      physiological regulation of insulin secretion performed by pancreatic beta cells.
      To obtain a better method through which to acquire more similar IPCs, we compared
      the difference between IPCs of the GLP-1 group and IPCs of the non-GLP-1 group in
      the morphological features in cellular level and physiological function. The
      levels of insulin secretion were measured by ELISA. The insulin and glucagon-like
      peptide-1 (GLP-1) mRNA gene expression was determined by real-time quantitative
      PCR. The morphological features were detected by atomic force microscopy (AFM)
      and laser confocal scanning microscopy (LCSM). Intracellular Ca(2+) levels and
      Glucagon-like peptide-1 receptor (GLP-1R) levels were determined by flow
      cytometer (FCM). We found that IPCs of the GLP-1 group had bigger membrane
      particle size and average roughness (Ra ) than IPCs of the non-GLP-1 group but
      still smaller than normal human pancreatic beta cells. The physiology function of
      IPCs of the GLP-1 group were much closer to normal human pancreatic beta cells
      than IPCs of the non-GLP-1 group. GLP-1 could improve the similarity of IPCs from
      human adipose tissue-derived mesenchymal stem cells and pancreatic beta cells in
      cellular ultrastructure and function.

PMID- 23553681
TI  - Age and sex differences in prevalence and clinical correlates of depression:
      first results from the Irish Longitudinal Study on Ageing.
AB  - OBJECTIVE: The risk of depression is increased by physical illness; however, the
      nature of this relationship is complex and unclear. Here, we explore the
      prevalence and clinical correlates of depression, with particular emphasis on
      factors representing consequences or physical manifestations of disease and
      identify age and gender differences in their effects. METHODS: A population
      representative sample of 8175 community-dwelling adults aged 50 years and over
      participated in the first wave of The Irish Longitudinal Study on Ageing. The
      primary outcome measure was clinically significant depressive symptoms defined by
      a score of 16 or greater on the 20-item Centre for Epidemiologic Studies
      Depression scale. RESULTS: Overall, 10% (95% CI: 9-11%) of adults reported
      clinically significant depressive symptoms. Physical illness is associated with
      depressive symptoms only in adults 65 years and older; in adults aged 50-64
      years, the association is mediated by medication use, and this age difference is
      statistically significant (p < 0.00). Irrespective of age, chronic pain and
      incontinence were stronger predictors of depression in men (interaction effects p
      < 0.00) CONCLUSIONS: Our findings identify age-specific and gender-specific
      clinical markers for depression risk among the older population, which may
      identify those more likely to present with depression in community settings.

PMID- 23553682
TI  - Total body computed tomography scan in the initial work-up of Binet stage A
      chronic lymphocytic leukemia patients: Results of the prospective, multicenter O
      CLL1-GISL study.
AB  - Total body computed tomography (TB-CT) scan is not mandatory in the
      diagnostic/staging algorithm of chronic lymphocytic leukemia (CLL). The aim of
      this study was to determine the value and prognostic significance of TB-CT scan
      in early stage CLL patients. Baseline TB-CT scan was performed in 240 Binet stage
      A CLL patients (179 Rai low- and 61 Rai intermediate-risk) included in a
      prospective multicenter observational study (clinicaltrial.gov ID:NCT00917549).
      The cohort included 69 clinical monoclonal B lymphocytosis (cMBLs). Patients were
      restaged considering only radiological data. Following TB-CT scans, 20% of cases
      reclassified as radiologic Binet (r-Binet) stage B. r-Binet B patients showed a
      higher incidence of unfavorable cytogenetic abnormalities (P = 0.027), as well as
      a shorter PFS (P = 0.001). At multivariate analysis, r-Binet stage [HR = 2.48; P
      = 0.004] and IGHV mutational status [HR = 3.01; P = 0.002] retained an
      independent predictive value for PFS. Among 179 Rai low-risk cases, 100 were
      redefined as r-Rai intermediate-risk based upon TB-CT scan data, showing a higher
      rate of cases with higher ZAP-70 (P = 0.033) and CD38 expression (P = 0.029) and
      beta2-microglobulin levels (P < 0.0001), as well as a shorter PFS than those with
      r-Rai low-risk (P = 0.008). r-Rai stage [HR = 2.78; P = 0.046] and IGHV
      mutational status [HR = 4.25; P = 0.009] retained a significant predictive value
      for PFS at multivariate analysis. Forty-two percent of cMBL patients were
      reclassified as r-small lymphocytic lymphomas (r-SLLs) by TB-CT scan. TB-CT scan
      appears to provide relevant information in early stage CLL related to the
      potential and the timing of patients to progress towards the more advanced
      disease stages.

PMID- 23553683
TI  - Perceptions of patient-provider communication in breast and cervical cancer
      related care: a qualitative study of low-income English- and Spanish-speaking
      women.
AB  - To explore patient perceptions of patient-provider communication in breast and
      cervical cancer-related care among low-income English- and Spanish-speaking
      women, we examined communication barriers and facilitators reported by patients
      receiving care at safety net clinics. Participants were interviewed in English or
      Spanish after receiving an abnormal breast or cervical cancer screening test or
      cancer diagnosis. Following an inductive approach, interviews were coded and
      analyzed by the language spoken with providers and patient-provider language
      concordance status. Of 78 participants, 53 % (n = 41) were English-speakers and
      47 % (n = 37) were Spanish-speakers. All English-speakers were language
      concordant with providers. Of Spanish-speakers, 27 % (n = 10) were Spanish
      concordant; 38 % (n = 14) were Spanish-discordant, requiring an interpreter; and
      35 % (n = 13) were Spanish mixed-concordant, experiencing both types of
      communication throughout the care continuum. English-speakers focused on
      communication barriers, and difficulty understanding jargon arose as a theme.
      Spanish-speakers emphasized communication facilitators related to Spanish
      language use. Themes among all Spanish-speaking sub-groups included appreciation
      for language support resources and preference for Spanish-speaking providers.
      Mixed-concordant participants accounted for the majority of Spanish-speakers who
      reported communication barriers. Our data suggest that, although perception of
      patient-provider communication may depend on the language spoken throughout the
      care continuum, jargon is lost when health information is communicated in
      Spanish. Further, the respective consistency of language concordance or
      interpretation may play a role in patient perception of patient-provider
      communication. 

PMID- 23553684
TI  - Estimating the impact of smoking cessation during pregnancy: the San Bernardino
      County experience.
AB  - We examined the relation between maternal smoking and adverse infant outcomes
      [low birth weight (LBW), and preterm birth (PTB)] during 2007-2008 in San
      Bernardino County, California-the largest county in the contiguous United States
      which has one of the highest rates of infant mortality in California. Using birth
      certificate data, we identified 1,430 mothers in 2007 and 1,355 in 2008 who
      smoked during pregnancy. We assessed the effect of never smoking and smoking
      cessation during pregnancy relative to smoking during pregnancy for the
      1,843/1,798 LBW, and 3,480/3,238 PTB's recorded for 2007/2008, respectively. To
      describe the effect of quitting smoking during pregnancy, we calculated the
      exposure impact number for smoking during pregnancy. Major findings are: (1)
      relative to smoking during pregnancy, significantly lower risk of LBW among never
      smoking mothers [OR, year: 0.56, 2007; 0.54, 2008] and for smoking cessation
      during pregnancy [0.57, 2007; 0.72, 2008]; (2) relative to smoking during
      pregnancy, significantly lower risk of PTB was found for never smoking mothers
      [0.68, 2007; 0.68, 2008] and for smoking cessation during pregnancy [0.69, 2007;
      0.69, 2008]; (3) an exposure impact assessment indicating each LBW or PTB outcome
      in the county could have been prevented either by at least 35 mothers quitting
      smoking during pregnancy or by 25 mothers being never smokers during pre
      pregnancy. Our findings identify an important burden of adverse infant outcomes
      due to maternal smoking in San Bernardino County that can be effectively
      decreased by maternal smoking cessation. 

PMID- 23553686
TI  - A series of 238 cytomegalovirus primary infections during pregnancy: description
      and outcome.
AB  - OBJECTIVE: To analyze the outcome of maternal primary cytomegalovirus (CMV)
      infection. METHODS: Retrospective analysis of a cohort of 238 patients with
      maternal primary CMV infection detected at routine screening. The cases were
      managed with serial ultrasound (US) scans, and amniocentesis was performed in
      36.1% of cases. All prenatal results were confirmed at birth. RESULTS: The
      average age was 31.9 (18-44) years. Patients were symptomatic in 21% of cases.
      The rate of intrauterine transmission was 24.9%, and it was 8.8%, 19%, 30.6%,
      34.1% and 40% in the preconceptional period, the periconceptional period, and the
      first, second and third trimesters of pregnancy, respectively (p = 0.025). There
      was a significantly higher risk of US abnormalities when maternal infection
      occurred during the preconceptional or periconceptional period and the first
      trimester compared with later (p < 0.001). Because of US abnormalities, pregnancy
      was terminated in 18 cases at the parents' request. Three infected newborns were
      symptomatic; all three cases were suspected at US before birth. We did not
      observe any symptomatic fetal infection when maternal infection occurred after 14
      weeks of gestation. A number of clinically asymptomatic cases (5.5%) developed
      hearing loss. CONCLUSION: The rate of materno fetal transmission is linearly
      correlated to the gestational age at infection. No severe case of congenital
      infection was observed if maternal infection occurred after 14 weeks of
      gestation.

PMID- 23553685
TI  - Predictors of hypertension among Filipino immigrants in the Northeast US.
AB  - Hypertension remains disproportionately high among Filipinos compared to other
      racial and ethnic minority populations, and little research on cardiovascular
      disease risk factors has been conducted among Filipino immigrants in the
      Northeastern part of the United States. To determine hypertension prevalence and
      risk factors among Filipino Americans in the New York City area, blood pressure
      and other clinical measurements were taken from a sample of Filipino Americans
      during 119 community health screenings conducted between 2006 and 2010.
      Additional socio-demographic and health-related characteristics were also
      collected via a cross-sectional survey. A total of 1,028 Filipino immigrants
      completed the survey and had clinical readings collected. Bivariate analyses and
      logistic regression were performed in order to predict and assess risk factors
      for hypertension among our sample. Fifty-three percent of individuals were
      hypertensive, and half of hypertensive individuals were uninsured. Logistic
      regression indicated that older age, male gender, living in the United States for
      over 5 years, a BMI greater than 23.0 kg/m(2), an elevated glucose reading, a
      family history of hypertension, and fair or poor self-reported health status were
      predictors of hypertension. There is a great need to develop more effective
      community-based interventions in the Filipino community to address cardiovascular
      health disparities. 

PMID- 23553687
TI  - Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers
      of microvascular invasion in hepatocellular carcinomas.
AB  - Microvascular invasion (MiVI) is a major risk factor in postoperative tumor
      recurrence and mortality in hepatocellular carcinoma (HCC). Unfortunately, this
      histological feature is usually missed by liver biopsy because of limited
      sampling, and MiVI is commonly detected only after surgery and examination of the
      full resected specimen. To date, there exists no reliable tool for identifying
      MiVI prior to surgical procedures. This study aimed to compare the proteome of
      HCC with and without MiVI in order to identify surrogate biomarkers of MiVI. A
      training cohort comprising surgically resected primary HCC with MiVI (n = 30) and
      without MiVI (n = 26) was subjected to matrix-assisted laser desorption
      ionization imaging mass spectrometry (MALDI IMS). Comparative analysis of
      acquired mass spectra of the two groups yielded 30 differential protein peaks,
      among which 28 were more strongly expressed in HCC with MiVI. Among these, two
      peaks were identified as N-term acetylated histone H4 dimethylated at lysine (K)
      20, and N-term acetylated histone H4 dimethylated at K20 and acetylated at K16.
      Both peaks were validated in the training cohort and in an independent validation
      cohort (n = 23) by immunohistochemistry and western blot. CONCLUSION: These
      results demonstrate the potential of MALDI IMS for uncovering new relevant
      biomarkers of MiVI in HCC, and highlight the role of epigenetic modifications in
      the prognosis of HCC. Preoperative detection of modified forms of histone H4
      expression in tumor biopsies would be helpful in management of patients with HCC.

PMID- 23553690
TI  - Time to Change from the perspective of a family member. Invited commentary
      on...Evaluation of England's Time to Change programme.
AB  - This commentary views the Time to Change programme from a triple perspective:
      that of a concerned family member, an academic investigator and an American. The
      programme's results are both encouraging and sobering. Progress has been made in
      employers' views, but mental health professionals remain a source of
      discrimination. Future initiatives must have realistic objectives, be
      multifaceted and avoid overzealous promises.

PMID- 23553688
TI  - Factors associated with uterine endometrial hyperplasia and pyometra in wild
      canids: implications for fertility.
AB  - The ability to safely and effectively manage reproduction is central to the
      success of AZA captive-breeding programs. Although the AZA Wildlife Contraception
      Center routinely monitors contraceptive safety, there have been no studies that
      compare the effects of contraceptive use to separation of males from females, the
      other option for preventing reproduction. We used retrospective medical records
      and pathology reports submitted by AZA and related facilities for the seven AZA
      managed canid species to assess rates of uterine pathology relative to female
      reproductive life histories. Our results showed that the prevalence of both
      pyometra and endometrial hyperplasia (EH) was associated not only with treatment
      with the two most common contraceptives (Suprelorin(r) and MGA implants) but also
      with the number of years barren (i.e., not producing a litter and not
      contracepted). Rates of pyometra and EH were especially high in African painted
      dogs and red wolves, but lowest in swift and fennec foxes. The number of years
      producing a litter had a low association, suggesting it could be protective
      against uterine pathology. A more recently developed Suprelorin(r) protocol using
      Ovaban(r) to prevent the initial stimulation phase, followed by implant removal
      when reversal is desired, may be a safer contraceptive option. These results
      concerning the relationship between reproductive management and uterine health
      have important implications for AZA-managed programs, since the unsustainability
      of many captive populations may be due at least in part to infertility. Managing
      a female's reproductive lifespan to optimize or maintain fertility will require a
      reconsideration of how breeding recommendations are formulated.

PMID- 23553689
TI  - Time to Change campaign through the eyes of a service user. Invited commentary
      on...Evaluation of England's Time to Change programme.
AB  - The Time to Change campaign and its evaluation in this supplement are looked at
      from a service user's perspective. A number of achievements are applauded, but
      pertinent questions about the campaign analysis are raised and a qualitative
      evaluation is called for.

PMID- 23553691
TI  - It is time to change our cultural context. Invited commentary on...Evaluation of
      England's Time to Change programme.
AB  - The Time to Change campaign in England has attempted to change attitudes to
      mental illness at population level. The concept of cultural context is introduced
      to look at how mental illness functions in society and whether any change in the
      current context is feasible.

PMID- 23553692
TI  - Time to change, time to evaluate. Invited commentary on...Evaluation of England's
      Time to Change programme.
AB  - Time to Change is the largest national programme to counter stigma ever
      undertaken. It demonstrates that stigmatisation and its consequences are
      gradually becoming recognised as the most important obstacle to the development
      of mental health programmes. It also demonstrates that they can be prevented or
      reduced. The programme's evaluation answered many questions but others remain -
      concerning the indicators of success and ways of assessing them and relevance of
      the programme's achievements. The programme and its evaluation are important
      steps in the development of anti-stigma programmes worldwide.

PMID- 23553693
TI  - Evaluation of the Time to Change programme in England 2008-2011.
AB  - Time to Change (TTC) is the largest-ever programme in England designed to reduce
      stigma and discrimination against people with mental health disorders. The TTC
      evaluation partner is the Institute of Psychiatry at King's College London. We
      give an overview of the TTC programme 2007-2011 and describe how it was
      evaluated, by introducing the seven interrelated papers in this supplement,
      which, taken together, describe a complex series of social interventions using a
      research design of hitherto unparalleled detail and comprehensiveness.

PMID- 23553694
TI  - Anti-stigma campaigns: time to change.
AB  - This evaluation of the Time to Change anti-stigma campaign in England represents
      a milestone in international stigma research. While showing some positive
      outcomes, the overall picture is mixed and falls short of the wholesale shift in
      attitudes that is needed. A new approach is proposed for the coming decades.

PMID- 23553695
TI  - Public knowledge, attitudes and behaviour regarding people with mental illness in
      England 2009-2012.
AB  - BACKGROUND: Public stigma against people with mental health problems is damaging
      to individuals with mental illness and is associated with substantial societal
      burden. AIMS: To investigate whether public knowledge, attitudes and behaviour in
      relation to people with mental health problems have improved among the English
      population since the inception of the Time To Change programme in 2009. METHOD:
      We analysed longitudinal trends in public knowledge, attitudes and behaviour
      between 2009 and 2012 among a nationally representative sample of English adults.
      RESULTS: There were improvements in intended behaviour (0.07 standard deviation
      units, 95% CI 0.01-0.14) and a non-significant trend for improvement in attitudes
      (P = 0.08) among the English population. There was, however, no significant
      improvement in knowledge or reported behaviour. CONCLUSIONS: The findings provide
      support for effectiveness of the national Time to Change programme against stigma
      and discrimination in improving attitudes and intended behaviour, but not
      knowledge, among the public in England.

PMID- 23553696
TI  - Experiences of discrimination among people using mental health services in
      England 2008-2011.
AB  - BACKGROUND: Research suggests that levels of discrimination against people using
      mental health services are high; however, reports of these people's experiences
      are rare. AIMS: To determine whether the Time to Change (TTC) programme target of
      5% reduction in discrimination has been achieved. METHOD: Separate samples of
      people using mental health services were interviewed annually from 2008 to 2011
      using the Discrimination and Stigma Scale to record instances of discrimination.
      RESULTS: Ninety-one per cent of participants reported one or more experiences of
      discrimination in 2008 compared with 88% in 2011 (z = -1.9, P = 0.05). The median
      negative discrimination score was 40% in 2008 and 28% in 2011 (Kruskal-Wallis
      chi(2) = 83.4, P<0.001). CONCLUSIONS: The proportion of participants experiencing
      no discrimination increased significantly over the course of TTC but by less than
      the initial target. The overall median discrimination score fell by 11.5%. Data
      from 2010 and 2011 suggest that these gains may be hard to maintain during
      economic austerity.

PMID- 23553697
TI  - Newspaper coverage of mental illness in England 2008-2011.
AB  - BACKGROUND: Better newspaper coverage of mental health-related issues is a target
      for the Time to Change (TTC) anti-stigma programme in England, whose population
      impact may be influenced by how far concurrent media coverage perpetuates stigma
      and discrimination. AIMS: To compare English newspaper coverage of mental health
      related topics each year of the TTC social marketing campaign (2009-2011) with
      baseline coverage in 2008. METHOD: Content analysis was performed on articles in
      27 local and national newspapers on two randomly chosen days each month. RESULTS:
      There was a significant increase in the proportion of anti-stigmatising articles
      between 2008 and 2011. There was no concomitant proportional decrease in
      stigmatising articles, and the contribution of mixed or neutral elements
      decreased. CONCLUSIONS: These findings provide promising results on improvements
      in press reporting of mental illness during the TTC programme in 2009-2011, and a
      basis for guidance to newspaper journalists and editors on reporting mental
      illness.

PMID- 23553698
TI  - Mental health problems in the workplace: changes in employers' knowledge,
      attitudes and practices in England 2006-2010.
AB  - BACKGROUND: In 2006 the Shaw Trust charity found high levels of ignorance and
      poor preparedness to deal with mental health problems among 480 senior employers
      in the UK. The UK government, non-governmental organisations and Time to Change
      (TTC) have since provided relevant assistance to employers. AIMS: To examine
      whether there have been improvements in mental health-related knowledge,
      attitudes and workplace practices among British senior employers between 2006 and
      2010. METHOD: A telephone survey was conducted of senior British employers (n =
      480 in 2006 and n = 500 in 2009 and 2010). RESULTS: An increased awareness of
      common mental health problems was detected. Employers continued to believe that
      job candidates should disclose a mental health problem, but became less likely to
      view colleagues' attitudes as a barrier to employing someone with such a problem.
      Formal policies on mental health and the use of workplace accommodations became
      increasingly common. CONCLUSIONS: These results are consistent with those of the
      TTC national public attitudes and the Viewpoint survey of service users between
      2008 and 2010, which showed improved public attitudes to mental illness and a
      reduction in experiences of discrimination in employment.

PMID- 23553699
TI  - Influence of Time to Change's social marketing interventions on stigma in England
      2009-2011.
AB  - BACKGROUND: England's Time To Change (TTC) social marketing campaign emphasised
      social contact between people with and without mental health problems to reduce
      stigma and discrimination. AIMS: We aimed to assess the effectiveness of the mass
      media component and also that of the mass social contact events. METHOD: Online
      interviews were performed before and after each burst of mass media social
      marketing to evaluate changes in knowledge, attitudes and behaviour and
      associations between campaign awareness and outcomes. Participants at social
      contact events were asked about the occurrence and quality of contact, attitudes,
      readiness to discuss mental health and intended behaviour towards people with
      mental health problems. RESULTS: Prompted campaign awareness was 38-64%. A
      longitudinal improvement was noted for one intended behaviour item but not for
      knowledge or attitudes. Campaign awareness was positively associated with greater
      knowledge (beta = 0.80, 95% CI 0.52-1.08) and more favourable attitudes
      (commonality OR 1.37, 95% CI 1.10-1.70; dangerousness OR 1.41, 95% CI 1.22-1.63)
      and intended behaviour (beta = 0.75, 95% CI 0.53-0.96). Social contact at events
      demonstrated a positive impact (M = 2.68) v. no contact (M = 2.42) on perceived
      attitude change; t(211) = 3.30, P = 0.001. Contact quality predicted more
      positive attitude change (r = 0.33, P<0.01) and greater confidence to challenge
      stigma (r = 0.38, P<0.01). CONCLUSIONS: The favourable short-term consequences of
      the social marketing campaign suggest that social contact can be used by anti
      stigma programmes to reduce stigma.

PMID- 23553700
TI  - Anti-stigma training for medical students: the Education Not Discrimination
      project.
AB  - BACKGROUND: Education Not Discrimination (END) is the component of the Time to
      Change programme intended to reduce mental health stigma among professionals and
      professional trainees. AIMS: To investigate the impact of the END anti-stigma
      programme on medical students immediately and after 6 months with regard to
      knowledge, attitudes, behaviour and empathy. METHOD: A total of 1452 medical
      students participated in the study (intervention group n = 1066, control group n
      = 386). Participants completed questionnaires at baseline, and at immediate and 6
      month follow-up. Groups were compared for changes in stigma outcomes. RESULTS:
      All measures improved in both groups, particularly among students with less
      knowledge and more stigmatising attitudes and intended behaviour at baseline. At
      immediate follow-up the intervention group demonstrated significantly greater
      improvements in stigma-related knowledge and reductions in stigma-related
      attitudes and intended behaviour, relative to the control group. At 6 months'
      follow-up, however, only one attitude item remained significantly better.
      CONCLUSIONS: Although the intervention produced short-term advantage there was
      little evidence for its persistent effect, suggesting a need for greater
      integration of ongoing measures to reduce stigma into the medical curriculum.

PMID- 23553701
TI  - Economic evaluation of the anti-stigma social marketing campaign in England 2009
      2011.
AB  - BACKGROUND: Evidence on the economic impact of social marketing anti-stigma
      campaigns in relation to people with mental illness is limited. AIMS: To describe
      the economic impact of the Time to Change (TTC) anti-stigma social marketing
      campaign, including the potential effects on the wider economy. METHOD: Data
      collected for the evaluation of TTC were combined with the social marketing
      campaign expenditure data to investigate differences in knowledge, attitudes and
      behaviour in relation to campaign awareness. To evaluate the return on
      investment, we applied a decision model that estimated the impact on employment
      for people with depression. RESULTS: Based on average national social marketing
      campaign costs, the economic benefits outweighed costs even if the campaign
      resulted in only 1% more people with depression accessing services and gaining
      employment if they experienced a health improvement. The cost per person with
      improved intended behaviour was at most L 4 if we assume the campaign was
      responsible for 50% of the change. Costs associated with improved knowledge and
      attitudes, however, were more variable. CONCLUSIONS: The findings suggest that
      the TTC anti-stigma social marketing campaign is a potentially cost-effective and
      low-cost intervention for reducing the impact of stigma on people with mental
      health problems.

PMID- 23553702
TI  - The Froment-Rauber nerve: a case report and review.
AB  - INTRODUCTION: The Froment-Rauber nerve is a rarely described anomalous nerve
      arising from 1 of the terminal branches of the radial nerve that provides
      innervation to intrinsic hand muscles. We describe a 26-year-old man who had a
      traumatic radial nerve injury that resulted in first dorsal interosseous muscle
      wasting. He presented to our clinic 2.5 years post-injury, after having had
      unnecessarily undergone surgical exploration of the ulnar nerve. METHODS: The
      patient's history, clinical examination, and multiple electrodiagnostic tests
      were reviewed. RESULTS: All findings were consistent with a diagnosis of
      anomalous innervation via a Froment-Rauber nerve. CONCLUSIONS: Understanding this
      rare phenomenon may aid in diagnosing confusing clinical cases and prevent
      unnecessary procedures.

PMID- 23553704
TI  - Winners of the 2012 American College of Rheumatology annual image competition.

PMID- 23553703
TI  - Reduced extracellular zinc levels facilitate glutamate-mediated oligodendrocyte
      death after trauma.
AB  - Spinal cord injury results in irreversible paralysis, axonal injury, widespread
      oligodendrocyte death, and white matter damage. Although the mechanisms
      underlying these phenomena are poorly understood, previous studies from our
      laboratory indicate that inhibiting activation of the nuclear factor-kappaB
      transcription factor in astrocytes reduces white matter damage and improves
      functional recovery following spinal cord injury. In the current study, we
      demonstrate that activation of the nuclear factor-kappaB transcription factor
      within astrocytes results in a significant increase in oligodendrocyte death
      following trauma by reducing extracellular zinc levels and inducing glutamate
      excitotoxicity. By using an ionotropic glutamate receptor antagonist (CNQX), we
      show that astroglial nuclear factor-kappaB-mediated oligodendrocyte death is
      dependent on glutamate signaling despite no change in extracellular glutamate
      concentrations. Further analysis demonstrated a reduction in levels of
      extracellular zinc in astrocyte cultures with functional nuclear factor-kappaB
      signaling following trauma. Cotreatment of oligodendrocytes with glutamate and
      zinc showed a significant increase in oligodendrocyte toxicity under low-zinc
      conditions, suggesting that the presence of zinc at specific concentrations can
      prevent glutamate excitotoxicity. These studies demonstrate a novel role for zinc
      in regulating oligodendrocyte excitotoxicity and identify new therapeutic targets
      to prevent oligodendrocyte cell death in central nervous system trauma and
      disease.

PMID- 23553707
TI  - Nitric oxide and energy metabolism in mammals.
AB  - Nitric oxide (NO) is a signaling molecule synthesized from L-arginine by NO
      synthase in animals. Increasing evidence shows that NO regulates the mammalian
      metabolism of energy substrates and that these effects of NO critically depend on
      its concentrations at the reaction site and the period of exposure. High
      concentrations of NO (in the micromolar range) irreversibly inhibit complexes I,
      II, III, IV, and V in the mitochondrial respiratory chain, whereas physiological
      levels of NO (in the nanomolar range) reversibly reduce cytochomrome oxidase.
      Thus, NO reduces oxygen consumption by isolated mitochondria to various extents.
      In intact cells, through cGMP and AMP-activated protein kinase signaling,
      physiological levels of NO acutely stimulate uptake and oxidation of glucose and
      fatty acids by skeletal muscle, heart, liver, and adipose tissue, while
      inhibiting the synthesis of glucose, glycogen and fat in the insulin-sensitive
      tissues, and enhancing lipolysis in white adipocytes. Chronic effects of
      physiological levels of NO in vivo include stimulation of angiogenesis, blood
      flow, mitochondrial biogenesis, and brown adipocyte development. Modulation of NO
      mediated pathways through dietary supplementation with L-arginine or its
      precursor L-citrulline may provide an effective, practical strategy to prevent
      and treat metabolic syndrome, including obesity, diabetes, and dyslipidemia in
      mammals, including humans.

PMID- 23553708
TI  - Impact of sildenafil on survival of patients with Eisenmenger syndrome.
AB  - The favorable effects of short-term use of sildenafil on patients with
      Eisenmenger syndrome have been reported. We further studied the impact of long
      term use of sildenafil on survival of these patients. In this study, the baseline
      data of patients newly diagnosed as Eisenmenger syndrome in our hospital between
      January 2005 and December 2009 were retrospectively collected. Patients were
      followed-up either by telephone contacts or during visits in our out-patient
      clinic. A total of 121 patients (68 patients in conventional group and 53
      patients in sildenafil group) were finally included and 29 patients were re
      evaluated after sildenafil therapy for 3-4 months. Compared with the baseline, a
      6-minute walk distance, functional classes, plasma hemoglobin level, and
      hemodynamics were significantly improved after sildenafil treatment. During a
      median follow-up period of 35.8 months, 15 patients died (11 patients in
      conventional group). The 1- and 3-year survival rates in sildenafil group were
      97.0% and 95.2%, significantly higher than 90.6% and 82.9% in conventional group
      P = .025). Multivariate analysis showed that sildenafil therapy, functional class
      and mean pulmonary arterial pressure were independently associated with survival.
      Therefore, long-term sildenafil therapy improved survival in patients with
      Eisenmenger syndrome.

PMID- 23553710
TI  - Synthesis of a targeted library of heparan sulfate hexa- to dodecasaccharides as
      inhibitors of beta-secretase: potential therapeutics for Alzheimer's disease.
AB  - Heparan sulfates (HS) are a class of sulfated polysaccharides that function as
      dynamic biological regulators of the functions of diverse proteins. The
      structural basis of these interactions, however, remains elusive, and chemical
      synthesis of defined structures represents a challenging but powerful approach
      for unravelling the structure-activity relationships of their complex sulfation
      patterns. HS has been shown to function as an inhibitor of the beta-site cleaving
      enzyme beta-secretase (BACE1), a protease responsible for generating the toxic
      Abeta peptides that accumulate in Alzheimer's disease (AD), with 6-O-sulfation
      identified as a key requirement. Here, we demonstrate a novel generic synthetic
      approach to HS oligosaccharides applied to production of a library of 16 hexa- to
      dodecasaccharides targeted at BACE1 inhibition. Screening of this library
      provided new insights into structure-activity relationships for optimal BACE1
      inhibition, and yielded a number of potent non-anticoagulant BACE1 inhibitors
      with potential for development as leads for treatment of AD through lowering of
      Abeta peptide levels.

PMID- 23553709
TI  - Membrane phospholipid bilayer as a determinant of monoacylglycerol lipase kinetic
      profile and conformational repertoire.
AB  - The membrane-associated serine hydrolase, monoacylglycerol lipase (MGL), is a
      well-recognized therapeutic target that regulates endocannabinoid signaling.
      Crystallographic studies, while providing structural information about static MGL
      states, offer no direct experimental insight into the impact of MGL's membrane
      association upon its structure-function landscape. We report application of
      phospholipid bilayer nanodiscs as biomembrane models with which to evaluate the
      effect of a membrane system on the catalytic properties and conformational
      dynamics of human MGL (hMGL). Anionic and charge-neutral phospholipid bilayer
      nanodiscs enhanced hMGL's kinetic properties [apparent maximum velocity (Vmax)
      and substrate affinity (Km)]. Hydrogen exchange mass spectrometry (HX MS) was
      used as a conformational analysis method to profile experimentally the extent of
      hMGL-nanodisc interaction and its impact upon hMGL structure. We provide evidence
      that significant regions of hMGL lid-domain helix alpha4 and neighboring helix
      alpha6 interact with the nanodisc phospholipid bilayer, anchoring hMGL in a more
      open conformation to facilitate ligand access to the enzyme's substrate-binding
      channel. Covalent modification of membrane-associated hMGL by the irreversible
      carbamate inhibitor, AM6580, shielded the active site region, but did not
      increase solvent exposure of the lid domain, suggesting that the inactive,
      carbamylated enzyme remains intact and membrane associated. Molecular dynamics
      simulations generated conformational models congruent with the open, membrane
      associated topology of active and inhibited, covalently-modified hMGL. Our data
      indicate that hMGL interaction with a phospholipid membrane bilayer induces
      regional changes in the enzyme's conformation that favor its recruiting
      lipophilic substrate/inhibitor from membrane stores to the active site via the
      lid, resulting in enhanced hMGL catalytic activity and substrate affinity.

PMID- 23553711
TI  - Impaired bone formation and increased osteoclastogenesis in mice lacking
      chemokine (C-C motif) ligand 5 (Ccl5).
AB  - Chemokines play crucial roles in the recruitment of specific hematopoietic cell
      types, and some of them have been suggested to be involved in the regulation of
      bone remodeling. Because we have previously observed that chemokine (C-C motif)
      ligand 2 (Ccl2) and Ccl5 are direct target genes of noncanonical Wnt signaling in
      osteoblasts, we analyzed the skeletal phenotypes of Ccl2-deficient and Ccl5
      deficient mice. In line with previous studies, Ccl2-deficient mice display a
      moderate reduction of osteoclastogenesis at the age of 6 months. In contrast, 6
      month-old Ccl5-deficient mice display osteopenia associated with decreased bone
      formation and increased osteoclastogenesis. Moreover, unlike in wild-type and
      Ccl2-deficient mice, large areas of their trabecular and endocortical bone
      surfaces are not covered by osteoblasts or bone-lining cells, and this is
      associated with a severe reduction of endosteal bone formation. Although this
      phenotype diminishes with age, it is important that we could further identify a
      reduced number of osteal macrophages in 6-month-old Ccl5-deficient mice, because
      this cell type has previously been reported to promote endosteal bone formation.
      Because Ccl5-deficient mice also display increased osteoclastogenesis, we finally
      addressed the question of whether osteal macrophages could differentiate into
      osteoclasts and/or secrete inhibitors of osteoclastogenesis. For that purpose we
      isolated these cells by CD11b affinity purification from calvarial cultures and
      characterized them ex vivo. Here we found that they are unable to differentiate
      into osteoblasts or osteoclasts, but that their conditioned medium mediates an
      antiosteoclastogenic effect, possibly caused by interleukin-18 (IL-18), an
      inhibitor of osteoclastogenesis expressed by osteal macrophages. Taken together,
      our data provide in vivo evidence supporting the previously suggested role of
      Ccl5 in bone remodeling. Moreover, to the best of our knowledge, Ccl5-deficient
      mice represent the first model with a spontaneous partial deficiency of osteal
      macrophages, a recently identified cell type, whose impact on bone remodeling is
      just beginning to be understood.

PMID- 23553712
TI  - Anatomical and mechanical relationship between the proximal attachment of
      adductor longus and the distal rectus sheath.
AB  - The objectives of this study were to investigate the anatomical relationship
      between the proximal adductor longus (AL) and rectus abdominis muscles and to
      determine whether unilateral loading of AL results in strain transmission across
      the anterior pubic symphysis to the contralateral distal rectus sheath. Bilateral
      dissections were conducted on 10 embalmed cadavers. Strain transfer across the
      pubic symphysis was examined on seven of these cadavers. An AL contraction was
      simulated by applying a controlled load in the direction of its proximal
      tendinous fibers, and the resultant strain in the contralateral distal rectus
      sheath was measured using a foil-type surface mounted microstrain gage. Adductor
      longus attached to the antero-inferior aspect of the pubis. In 18 of the 20
      limbs, the proximal attachment of AL was tendinous on its superficial surface and
      muscular on its deep surface. The proximal AL tendon was found in most instances
      to have secondary communications with structures such as the contralateral distal
      rectus sheath, pubic symphysis anterior capsule, ilio-inguinal ligament, and
      contralateral proximal AL tendon. Despite these consistent anatomical
      observations, strain measured in the contralateral distal rectus sheath upon
      unilateral loading of the proximal AL varied considerably between cadavers.
      Measured strain had an average +/- 1SD of 0.23 +/- 0.43%. The proximal attachment
      of AL contributes to an anatomical pathway across the anterior pubic symphysis
      that is likely required to withstand the transmission of large forces during
      multidirectional athletic activities. This anatomical relationship may be a
      relevant factor in explaining the apparent vulnerability of the AL and rectus
      abdominis attachments to injury.

PMID- 23553713
TI  - Evolution of electron-boson spectral density in the underdoped region of Bi2Sr(2
      x)La(x)CuO6.
AB  - We use a maximum entropy technique to obtain the electron-boson spectral density
      from optical scattering rate data across the underdoped region of the Bi2Sr(2
      x)La(x)CuO6 (Bi-2201) phase diagram. Our method involves a generalization of
      previous work which explicitly includes finite temperature and the opening of a
      pseudogap which modifies the electronic structure. We find that the mass
      enhancement factor lambda associated with the electron-boson spectral density
      increases monotonically with reduced doping and closer proximity to the Mott
      antiferromagnetic insulating state. This observation is consistent with increased
      coupling to the spin fluctuations. At the same time the system has reduced
      metallicity because of increased pseudogap effects which we model with a reduced
      effective density of states around the Fermi energy with the range of the
      modifications in energy set by the pseudogap scale.

PMID- 23553714
TI  - Using group-based latent class transition models to analyze chronic disability
      data from the National Long-Term Care Survey 1984-2004.
AB  - Latent class transition models track how individuals move among latent classes
      through time, traditionally assuming a complete set of observations for each
      individual. In this paper, we develop group-based latent class transition models
      that allow for staggered entry and exit, common in surveys with rolling
      enrollment designs. Such models are conceptually similar to, but structurally
      distinct from, pattern mixture models of the missing data literature. We employ
      group-based latent class transition modeling to conduct an in-depth data analysis
      of recent trends in chronic disability among the U.S. elderly population. Using
      activities of daily living data from the National Long-Term Care Survey (NLTCS),
      1982-2004, we estimate model parameters using the expectation-maximization
      algorithm, implemented in SAS PROC IML. Our findings indicate that declines in
      chronic disability prevalence, observed in the 1980s and 1990s, did not continue
      in the early 2000s as previous NLTCS cross-sectional analyses have indicated.

PMID- 23553715
TI  - Transferable and flexible label-like macromolecular memory on arbitrary
      substrates with high performance and a facile methodology.
AB  - A newly designed transferable and flexible label-like organic memory based on a
      graphene electrode behaves like a sticker, and can be readily placed on desired
      substrates or devices for diversified purposes. The memory label reveals
      excellent performance despite its physical presentation. This may greatly extend
      the memory applications in various advanced electronics and provide a simple
      scheme to integrate with other electronics.

PMID- 23553716
TI  - International examples of undocumented immigration and the affordable care act.
AB  - As it stands there is no viable health care option for undocumented immigrants of
      low socioeconomic status. Even more worrisome is that Affordable Care Act simply
      does not address this issue with any direct plan. The US is in a very influential
      time period in terms of undocumented immigration and its relationship with health
      care. The purpose of this paper is to examine international examples of
      undocumented immigrant health care and their implications for the United States'
      undocumented immigrant health care. This study found that physicians in the US
      must work to prevent the initiation of policies which exclude undocumented
      immigrants from accessing health care. Exclusionary policies implemented in
      European nations have had disastrous effects on physicians and patients. This
      paper examines the implications which similar policies would have if implemented
      in the US. 

PMID- 23553718
TI  - Pegylated interferon and ribavirin: a therapeutic option in patients who fail to
      respond to telaprevir-based triple therapy?

PMID- 23553719
TI  - Novel role of miR-181a in cartilage metabolism.
AB  - Micro RNA (miRNA) is a small non-coding post-transcriptional RNA regulator that
      is involved in a variety of biological events. In order to specify the role of
      miRNAs in cartilage metabolism, we comparatively analyzed the expression profile
      of known miRNAs in chicken sternum chondrocytes representing early and late
      differentiation stages. Interestingly, none of the miRNAs displaying strong
      expression levels showed remarkable changes along with differentiation,
      suggesting their roles in maintaining the homeostasis rather than
      cytodifferentiation of chondrocytes. Among these miRNAs, miR-181a, which is known
      to play critical roles in a number of tissues, was selected and was further
      characterized. Human microarray analysis revealed remarkably stronger expression
      of miR-181a in human HCS-2/8 cells, which strongly maintained a chondrocytic
      phenotype, than in HeLa cells, indicating its significant role in chondrocytes.
      Indeed, subsequent investigation indicated that miR-181a repressed the expression
      of two genes involved in cartilage development. One was CCN family member 1
      (CCN1), which promotes chondrogenesis; and the other, the gene encoding the core
      protein of aggrecan, a major cartilaginous proteoglycan, aggrecan. Based on these
      findings, negative feedback system via miR-181a to conserve the integrity of the
      cartilaginous phenotype may be proposed.

PMID- 23553720
TI  - Quantifying catch-and-release: the extensor tendon force needed to overcome the
      catching flexors in trigger fingers.
AB  - The extensor tendon forces required to overcome the catching flexors in trigger
      fingers are unknown. A biomechanical model with moment equilibrium equations and
      method of least squares was developed for estimating the tendon force at
      triggering in trigger fingers. Trigger fingers that exhibited significant
      catching and sudden release during finger extension were tested. A customized
      "pulling tester" was used to pull the finger from flexion to extension and
      provide synchronic measurement of the pulling force. The displacement of the
      tested finger was measured by a motion capture system. This preliminary study
      presents kinematic and kinetic data at triggering of 10 trigger fingers. The
      distal and proximal interphalangeal (PIP) joints presented sudden release while
      the metacarpophalangeal (MCP) joint started extension in the early phase of
      finger extension. The tendon tension of flexor digitorum profundus was greater
      than that of flexor digitorum superficialis (FDS) in six fingers, and less than
      that of FDS in three fingers. The tension of two flexor tendons was almost equal
      in one finger. At the PIP and MCP joints, 1.54 times the force of flexors was
      needed for the extensors to overcome the catching flexors in trigger fingers.
      This biomechanical model provides clinicians with a clearer idea of the tendon
      force at triggering. The quantitative results may help in the understanding of
      movement characteristics of trigger fingers. These findings are useful to better
      understand the etiology and nature of trigger finger development, and thus aid in
      further development of better assessments and treatments related to this.

PMID- 23553721
TI  - Secreted proteases of Trypanosoma brucei gambiense: possible targets for sleeping
      sickness control?
AB  - Human African trypanosomiasis (HAT) is caused by trypanosomes of the species
      Trypanosoma brucei and belongs to the neglected tropical diseases. Presently, WHO
      has listed 36 countries as being endemic for sleeping sickness. No vaccine is
      available, and disease treatment is difficult and has life-threatening side
      effects. Therefore, there is a crucial need to search for new therapeutic targets
      against the parasite. Trypanosome excreted-secreted proteins could be promising
      targets, as the total secretome was shown to inhibit, in vitro, host dendritic
      cell maturation and their ability to induce lymphocytic allogenic responses. The
      secretome was found surprisingly rich in various proteins and unexpectedly rich
      in diverse peptidases, covering more than ten peptidase families or subfamilies.
      Given their abundance, one may speculate that they would play a genuine role not
      only in classical "housekeeping" tasks but also in pathogenesis. The paper
      reviews the deleterious role of proteases from trypanosomes, owing to their
      capacity to degrade host circulating or structural proteins, as well as proteic
      hormones, causing severe damage and preventing host immune response. In addition,
      proteases account for a number of drug targets, such drugs being used to treat
      severe diseases such AIDS. This review underlines the importance of secreted
      proteins and especially of secreted proteases as potential targets in HAT
      fighting strategies. It points out the need to conduct further investigations on
      the specific role of each of these various proteases in order to identify those
      playing a central role in sleeping sickness and would be suitable for drug
      targeting.

PMID- 23553722
TI  - Concurrent polycythemia vera and chronic lymphocytic leukemia: treatment response
      to pegylated interferon alpha 2a.

PMID- 23553723
TI  - C-Glycosyl amino acids through hydroboration-cross-coupling of exo-glycals and
      their application in automated solid-phase synthesis.
AB  - O-Glycosylation is one of the most important post-translational modifications of
      proteins. The attachment of carbohydrates to the peptide backbone influences the
      conformation as well as the solubility of the conjugates and can even be
      essential for binding to specific ligands in cell-cell interactions or for active
      transport over membranes. This makes glycopeptides an interesting class of
      compounds for medical applications. To enhance the long-term availability of
      these molecules in vivo, the stabilization of the glycosidic bond between the
      amino acid residue and the carbohydrate is of interest. The described modular
      approach affords beta-linked C-glycosyl amino acids by a sequence of Petasis
      olefination of glyconolactones, stereoselective hydroboration and a mild B-alkyl
      Suzuki coupling reaction. The coupling products were transformed to C-glycosyl
      amino acid building-blocks suitable for solid-phase synthesis and successfully
      incorporated into a partial sequence of the tumor-associated MUC1-glycopeptide.
      The resulting C-glycopeptides are candidates for the development of long-term
      stable mimics of O-glycopeptide vaccines.

PMID- 23553724
TI  - Compatible fungi, suitable medium, and appropriate developmental stage essential
      for stable association of Dendrobium chrysanthum.
AB  - Establishment of symbiotic association at the appropriate developmental stage
      helped maintain continued growth which is vital for the long-term ex vitro
      survival of the orchid. In the present study, symbiotic association was carried
      out using different developmental stages of Dendrobium chrysanthum and pathogenic
      Rhizoctonia isolates (obtained from orchids and non-orchid hosts) in different
      culture media. Isolate 2162 supported highest symbiotic germination on OMA-S (oat
      meal agar medium without nutrients + sucrose), whereas, stable symbiotic
      association with plantlets was obtained with isolate 4634 on OMA-NC (oat meal
      agar medium + cellulose). Isolate Dc-2S2 obtained from the host plant did not
      promote seed germination nor did it form association with protocorms or
      plantlets. This study, for the first time identifies a combination of compatible
      fungal isolate, suitable culture medium, and appropriate developmental stage at
      which symbiotic association in vitro can be deemed successful for the medicinally
      important orchid, D. chrysanthum. 

PMID- 23553725
TI  - A method for processing multivariate data in medical studies.
AB  - Traditional displays of principal component analyses lack readability to
      discriminate between putative clusters of variables or cases. Here, the author
      proposes a method that clusterizes and visualizes variables or cases through
      principal component analyses thus facilitating their analysis. The method
      displays pre-determined clusters of variables or cases as urchins that each has a
      soma (the average point) and spines (the individual variables or cases). Through
      three examples in the field of neuropsychology, the author illustrates how
      urchins help examine the modularity of cognitive tasks on the one hand and
      identify groups of healthy versus brain-damaged participants on the other hand.
      Some of the data used in this article were obtained from the Alzheimer's Disease
      Neuroimaging Initiative database. The urchin method was implemented in MATLAB,
      and the source code is available in the Supporting information. Urchins can be
      useful in biomedical studies to identify distinct phenomena at first glance, each
      having several measures (clusters of variables) or distinct groups of
      participants (clusters of cases).

PMID- 23553726
TI  - Effects of acute and chronic morphine on delay discounting in pigeons.
AB  - When reinforcers of different magnitudes are concurrently available, choice is
      greater for a large reinforcer; that choice can be reduced by delaying its
      delivery, a phenomenon called delay discounting and represented graphically by a
      delay curve in which choice is plotted as a function of delay to the large
      reinforcer. Morphine, administered acutely, can alter responding for large,
      delayed reinforcers. In this study, the impact of morphine tolerance, dependence
      and withdrawal on choice of delayed reinforcers was examined in six pigeons
      responding to receive a small amount of food delivered immediately or a larger
      amount delivered immediately or after delays that increased within sessions.
      Acutely, morphine decreased responding for the large reinforcer, and the effect
      was greater when morphine was administered immediately, rather than 6 hr, before
      sessions. During 8 weeks of daily administration, morphine produced differential
      effects across pigeons, shifting the delay curve downward in some and upward in
      others. In all pigeons, tolerance developed to the response-rate-decreasing
      effects of morphine but not to its effects on delay discounting. When chronic
      morphine treatment was discontinued, rate of responding decreased in four
      pigeons, indicating the emergence of withdrawal; choice of the large reinforcer
      increased, regardless of delay, in all pigeons, an effect that persisted for
      weeks. These data suggest that chronic morphine administration has long-lasting
      effects on choice behavior, which might impact vulnerability to relapse in opioid
      abusers.

PMID- 23553727
TI  - Behavioral and structural effects of unilateral intrastriatal injections of
      botulinum neurotoxin a in the rat model of Parkinson's disease.
AB  - Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from
      presynaptic vesicles through its proteinase activity cleaving the SNARE complex.
      Parkinson's disease (PD) is associated with locally increased cholinergic
      activity in the striatum. Therefore, the present study investigates the effect of
      unilateral intrastriatal BoNT-A injection in naive rats on striatal morphology;
      i.e., the total number of Nissl-stained neurons and the volume of caudate-putamen
      (CPu) were estimated. Furthermore, stainings for markers of gliosis (glial
      fibrillary acidic protein) and microglia (Iba1) were performed. In addition, the
      potential beneficial effects of a unilateral intrastriatal injection of BoNT-A on
      motor activity in the rat model of hemi-PD were evaluated. Hemi-PD was induced by
      unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial
      forebrain bundle. Six weeks later, rats received an ipsilateral intrastriatal
      injection of BoNT-A. Behaviorally, motor performance was tested. The total number
      of CPu neurons and the striatal volume were not significantly different between
      the BoNT-A-injected right and the intact left hemispheres of naive rats. In hemi
      PD rats, intrastriatal BoNT-A abolished apomorphine-induced rotations, increased
      amphetamine-induced rotations, and tended to improve left forelimb usage. Forced
      motor function in the accelerod test was not significantly changed by BoNT-A, and
      open field activity was also unaltered compared with sham treatment. Thus,
      intrastriatal BoNT-A affects spontaneous motor activity of hemi-PD rats to a
      minor degree compared with drug-induced motor function. In the future, tests
      assessing the cognitive and emotional performance should be performed to
      ascertain finally the potential therapeutic usefulness of intrastriatal BoNT-A
      for PD.

PMID- 23553728
TI  - Re-analysis of an original CMTX3 family using exome sequencing identifies a known
      BSCL2 mutation.
AB  - INTRODUCTION: Charcot-Marie-Tooth (CMT) disease is a group of peripheral
      neuropathies affecting both motor and sensory nerves. CMTX3 is an X-linked CMT
      locus, which maps to chromosome Xq26.3-q27.3. Initially, CMTX3 was mapped to a
      31.2-Mb region in 2 American families. We have reexamined 1 of the original
      families (US-PED2) by next generation sequencing. METHODS: Three members of the
      family underwent exome sequencing. Candidate variants were validated by PCR and
      Sanger sequencing analysis. CONCLUSION: No pathogenic coding variants localizing
      to the CMTX3 region were identified. However, exome sequencing identified a known
      BSCL2 mutation (N88S). This study demonstrates the power of exome sequencing as a
      tool to identify gene mutations for a small family in the absence of
      statistically significant linkage data.

PMID- 23553729
TI  - Fully automated on-screen carotid intima-media thickness measurement: a screening
      tool for subclinical atherosclerosis.
AB  - PURPOSE: Carotid intima-media thickness (CIMT) is generally considered an
      appropriate direct vascular method for cardiovascular risk assessment. The
      objective of this study was to evaluate the feasibility and reproducibility of a
      newly developed automated on-screen carotid ultrasound with respect to manual
      measurement with a conventional system. METHODS: We assessed CIMT in 50
      consecutive patients (age 62 +/- 5 years, range 21-79 years, 36 men) twice, using
      a newly developed automated ultrasound (CardioHealth Station) and a conventional
      system with manual measurement (Acuson, Sequoia). For each patient, three frozen
      frames of the distal 10 mm of the right and left common carotid arteries were
      acquired on the two systems, by operators blinded to each other. The average of
      the mean value of three readings of each system was calculated. RESULTS: The
      intraclass correlation coefficient of the interoperator variability was 0.95 and
      0.94 for the automated and manual measurements, respectively. The comparative
      coefficient of variation of the interoperator variability was 8.2 and 8.7% for
      the automated and manual measurements, respectively. There was no clinically
      relevant difference between measurements obtained by the two systems (intraclass
      correlation coefficient = 0.98). The acquisition time of the automated system was
      significantly shorter than the conventional system (p < 0.01). CONCLUSIONS: Fully
      automated on-screen measurements of CIMT are feasible, faster, and as
      reproducible as conventional manual measurements and may be suitable and cost
      effective for screening application in community medicine.

PMID- 23553730
TI  - Structure-based network analysis of an evolved G protein-coupled receptor
      homodimer interface.
AB  - Crystallographic structures and experimental assays of human CXC chemokine
      receptor type 4 (CXCR4) provide strong evidence for the capacity to homodimerize,
      potentially as a means of allosteric regulation. Even so, how this homodimer
      forms and its biological significance has yet to be fully characterized. By
      applying principles from network analysis, sequence-based approaches such as
      statistical coupling analysis to determine coevolutionary residues, can be used
      in conjunction with molecular dynamics simulations to identify residues relevant
      to dimerization. Here, the predominant coevolution sector lies along the observed
      dimer interface, suggesting functional relevance. Furthermore, coevolution
      scoring provides a basis for determining significant nodes, termed hubs, in the
      network formed by residues found along the interface of the homodimer. These node
      residues coincide with hotspots indicating potential druggability. Drug design
      efforts targeting such key residues could potentially result in modulation of
      binding and therapeutic benefits for disease states, such as lung cancers,
      lymphomas and latent HIV-1 infection. Furthermore, this method may be applied to
      any protein-protein interaction.

PMID- 23553731
TI  - Gestational age and maternal weight effects on fetal cell-free DNA in maternal
      plasma.
AB  - OBJECTIVE: To determine the effects of gestational age and maternal weight on
      percent fetal cell-free DNA (cfDNA) in maternal plasma and the change in fetal
      cfDNA amounts within the same patient over time. METHODS: The cfDNA was extracted
      from maternal plasma from 22 384 singleton pregnancies of at least 10 weeks
      gestation undergoing the Harmony(TM) Prenatal Test. The Harmony Prenatal Test
      determined fetal percentage via directed analysis of cfDNA. RESULTS: At 10 weeks
      0 days to 10 weeks 6 days gestation, the median percent fetal cfDNA was 10.2%.
      Between 10 and 21 weeks gestation, percent fetal increased 0.1% per week (p <
      0.0001), and 2% of pregnancies were below 4% fetal cfDNA. Beyond 21 weeks
      gestation, fetal cfDNA increased 1% per week (p < 0.0001). Fetal cfDNA percentage
      was proportional to gestational age and inversely proportional to maternal weight
      (p = 0.0016). Of 135 samples that were redrawn because of insufficient fetal
      cfDNA of the initial sample, 76 (56%) had greater than 4% fetal cfDNA in the
      sample from the second draw. CONCLUSION: Fetal cfDNA increases with gestation,
      decreases with increasing maternal weight, and generally improves upon a blood
      redraw when the first attempt has insufficient fetal cfDNA.

PMID- 23553732
TI  - Ubiquitin E3 ligase Wwp1 negatively regulates osteoblast function by inhibiting
      osteoblast differentiation and migration.
AB  - Ubiquitin E3 ligase-mediated protein degradation promotes proteasomal degradation
      of key positive regulators of osteoblast functions. For example, the E3 ligases-
      SMAD-specific E3 ubiquitin protein ligase 1 (Smurf1), Itch, and WW domain
      containing E3 ubiquitin protein ligase 1 (Wwp1)--promote degradation of Runt
      related transcription factor 2 (Runx2), transcription factor jun-B (JunB), and
      chemokine (C-X-C) receptor type 4 (CXCR-4) proteins to inhibit their functions.
      However, the role of E3 ligases in age-associated bone loss is unknown. We found
      that the expression level of Wwp1, but not Smurf1 or Itch, was significantly
      increased in CD45-negative (CD45(-)) bone marrow-derived mesenchymal stem cells
      from 6-month-old and 12-month-old wild-type (WT) mice. Wwp1 knockout (Wwp1(-/-))
      mice developed increased bone mass as they aged, associated with increased bone
      formation rates and normal bone resorption parameters. Bone marrow stromal cells
      (BMSCs) from Wwp1(-/-) mice formed increased numbers and areas of alkaline
      phosphatase(+) and Alizarin red(+) nodules and had increased migration potential
      toward chemokine (C-X-C motif) ligand 12 (CXCL12) gradients. Runx2, JunB, and
      CXCR-4 protein levels were significantly increased in Wwp1(-/-) BMSCs. Wwp1(-/-)
      BMSCs had increased amount of ubiquitinated JunB protein, but Runx2
      ubiquitination was no change. Knocking down JunB in Wwp1(-/-) BMSCs returned
      Runx2 protein levels to that in WT cells. Thus, Wwp1 negatively regulates
      osteoblast functions by affecting both their migration and differentiation.
      Mechanisms designed to decrease Wwp1 levels in BMSCs may represent a new approach
      to prevent the decrease in osteoblastic bone formation associated with aging.

PMID- 23553733
TI  - Reply: To PMID 22610885.

PMID- 23553734
TI  - A secure and efficient password-based user authentication scheme using smart
      cards for the integrated EPR information system.
AB  - The integrated EPR information system supports convenient and rapid e-medicine
      services. A secure and efficient authentication scheme for the integrated EPR
      information system provides safeguarding patients' electronic patient records
      (EPRs) and helps health care workers and medical personnel to rapidly making
      correct clinical decisions. Recently, Wu et al. proposed an efficient password
      based user authentication scheme using smart cards for the integrated EPR
      information system, and claimed that the proposed scheme could resist various
      malicious attacks. However, their scheme is still vulnerable to lost smart card
      and stolen verifier attacks. This investigation discusses these weaknesses and
      proposes a secure and efficient authentication scheme for the integrated EPR
      information system as alternative. Compared with related approaches, the proposed
      scheme not only retains a lower computational cost and does not require verifier
      tables for storing users' secrets, but also solves the security problems in
      previous schemes and withstands possible attacks.

PMID- 23553735
TI  - Effectiveness of MR angiography for the primary diagnosis of acute pulmonary
      embolism: clinical outcomes at 3 months and 1 year.
AB  - PURPOSE: To determine the effectiveness of MR angiography for pulmonary embolism
      (MRA-PE) in symptomatic patients. MATERIALS AND METHODS: We retrospectively
      reviewed all patients whom were evaluated for possible pulmonary embolism (PE)
      using MRA-PE. A 3-month and 1-year from MRA-PE electronic medical record (EMR)
      review was performed. Evidence for venous thromboembolism (VTE) (or death from
      PE) within the year of follow-up was the outcome surrogate for this study.
      RESULTS: There were 190 MRA-PE exams performed with 97.4% (185/190) of diagnostic
      quality. There were 148 patients (120 F: 28 M) that had both a diagnostic MRA-PE
      exam and 1 complete year of EMR follow-up. There were 167 patients (137 F: 30 M)
      with 3 months or greater follow-up. We found 83% (139/167) and 81% (120/148) MRA
      PE exams negative for PE at 3 months and 1 year, respectively. Positive exams for
      PE were seen in 14% (23/167). During the 1-year follow-up period, five patients
      (false negative) were diagnosed with DVT (5/148 = 3.4 %), and one of these
      patients also experienced a non-life-threatening PE. The negative predictive
      value (NPV) for MRA-PE was 97% (92-99; 95% CI) at 3 months and 96% (90-98; 95%
      CI) with 1 year of follow-up. CONCLUSION: The NPV of MRA-PE, when used for the
      primary diagnosis of pulmonary embolism in symptomatic patients, were found to be
      similar to the published values for CTA-PE. In addition, the technical success
      rate and safety of MRA-PE were excellent.

PMID- 23553736
TI  - Mutations in the C-terminal domain of ColQ in endplate acetylcholinesterase
      deficiency compromise ColQ-MuSK interaction.
AB  - Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is mostly
      composed of an asymmetric form in which three tetramers of catalytic AChE
      subunits are linked to a triple helical collagen Q (ColQ). Mutations in COLQ
      cause endplate AChE deficiency. We report three patients with endplate AChE
      deficiency with five recessive COLQ mutations. Sedimentation profiles showed that
      p.Val322Asp and p.Arg227X, but not p.Cys444Tyr, p.Asp447His, or p.Arg452Cys,
      inhibit formation of triple helical ColQ. In vitro overlay of mutant ColQ-tailed
      AChE on muscle sections of Colq(-/-) mice revealed that p.Cys444Tyr, p.Asp447His,
      and p.Arg452Cys in the C-terminal domain (CTD) abrogate anchoring ColQ-tailed
      AChE to the NMJ. In vitro plate-binding assay similarly demonstrated that the
      three mutants inhibit binding of ColQ-tailed AChE to MuSK. We also confirmed the
      pathogenicity of p.Asp447His by treating Colq(-/-) mice with adeno-associated
      virus serotype 8 carrying mutant COLQ-p.Asp447His. The treated mice showed no
      improvement in motor functions and no anchoring of ColQ-tailed AChE at the NMJ.
      Electroporation of mutant COLQ harboring p.Cys444Tyr, p.Asp447His, and
      p.Arg452Cys into anterior tibial muscles of Colq(-/-) mice similarly failed to
      anchor ColQ-tailed AChE at the NMJ. We proved that the missense mutations in ColQ
      CTD cause endplate AChE deficiency by compromising ColQ-MuSK interaction at the
      NMJ.

PMID- 23553737
TI  - The matricellular protein CCN1 suppresses lung cancer cell growth by inducing
      senescence via the p53/p21 pathway.
AB  - CCN1, a secreted matrix-associated molecule, is involved in multiple cellular
      processes. Previous studies have indicated that expression of CCN1 correlates
      inversely with the aggressiveness of non-small-cell lung carcinoma (NSCLC);
      however, the underlying mechanisms remain elusive. Using three NSCLC cell line
      systems, here we show that long-term treatment of cells with the recombinant CCN1
      protein led to a permanent cell cycle arrest in G1 phase; cells remained viable
      as judged by apoptotic assays. CCN1-treated NSCLC cells acquired a phenotype
      characteristic of senescent cells, including an enlarged and flattened cell shape
      and expression of the senescence-associated beta-galactosidase. Immunoblot
      analysis showed that addition of CCN1 increased the abundance of hypo
      phosphorylated Rb, as well as accumulation of p53 and p21. Silencing the
      expression of p53 or p21 by lentivirus-mediated shRNA production in cells blocked
      the CCN1-induced senescence. Furthermore, a CCN1 mutant defective for binding
      integrin alpha6beta1 and co-receptor heparan sulfate proteoglycans was incapable
      of senescence induction. Our finding that direct addition of CCN1 induces
      senescence in NSCLC cells provides a potential novel strategy for therapeutic
      intervention of lung cancers.

PMID- 23553738
TI  - Brief report: rheumatoid arthritis is associated with left ventricular concentric
      remodeling: results of a population-based cross-sectional study.
AB  - OBJECTIVE: To study left ventricular (LV) geometry in patients with rheumatoid
      arthritis (RA) and no history of heart failure compared with that in subjects
      with neither RA nor a history of heart failure, and to determine the impact of RA
      on LV remodeling. METHODS: A cross-sectional, community-based study was conducted
      among adult (age >=50 years) patients with RA and age- and sex-matched subjects
      with neither RA nor a history of heart failure. All participants underwent
      standard 2-dimensional Doppler echocardiography. LV geometry was classified into
      the following 4 categories based on relative wall thickness and sex-specific
      cutoffs for the LV mass index: concentric remodeling, concentric hypertrophy,
      eccentric hypertrophy, or normal geometry. RESULTS: Among 200 patients with RA
      and 600 age- and sex-matched subjects without RA, the mean age was 65 years, and
      74% of the individuals in both cohorts were female. Compared with subjects
      without RA, patients with RA were significantly more likely to have abnormal LV
      geometry (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.03-2.00), even
      after adjusting for cardiovascular risk factors and comorbidities. Among subjects
      with abnormal LV geometry, the odds of concentric LV remodeling were
      significantly increased in patients with RA (OR 4.73, 95% CI 2.85-7.83). In
      linear regression analyses, the LV mass index appeared to be lower in patients
      with RA who were currently receiving corticosteroids (beta +/- SE -0.082 +/-
      0.027, P = 0.002), even after adjusting for cardiovascular risk factors and
      comorbidities. CONCLUSION: RA was strongly associated with abnormal LV remodeling
      (particularly concentric LV remodeling) among RA patients without heart failure.
      This association remained significant after adjustment for cardiovascular risk
      factors and comorbidities. RA disease-related factors may promote changes in LV
      geometry. The biologic mechanisms underlying LV remodeling warrant further
      investigation.

PMID- 23553739
TI  - Package-free flexible organic solar cells with graphene top electrodes.
AB  - Package-free flexible organic solar cells are fabricated with multilayer graphene
      as top transparent electrodes, which show the highest power conversion efficiency
      of about 3.2% and excellent flexibility and bending stability. The devices also
      show good air stability, indicating that multilayer graphene is a promising
      environmental barrier that can protect the organic solar cells from air
      contamination. 

PMID- 23553740
TI  - Human myogenic endothelial cells exhibit chondrogenic and osteogenic potentials
      at the clonal level.
AB  - We have previously reported the high regenerative potential of murine muscle
      derived stem cells (mMDSCs) that are capable of differentiating into multiple
      mesodermal cell lineages, including myogenic, endothelial, chondrocytic, and
      osteoblastic cells. Recently, we described a putative human counterpart of
      mMDSCs, the myogenic endothelial cells (MECs), in adult human skeletal muscle,
      which efficiently repair/regenerate the injured and dystrophic skeletal muscle as
      well as the ischemic heart in animal disease models. Nevertheless it remained
      unclear whether human MECs, at the clonal level, preserve mMDSC-like chondrogenic
      and osteogenic potentials and classic stem cell characteristics including high
      proliferation and resistance to stress. Herein, we demonstrated that MECs, sorted
      from fresh postnatal human skeletal muscle biopsies, can be grown clonally and
      exhibit robust resistance to oxidative stress with no tumorigeneity. MEC clones
      were capable of differentiating into chondrocytes and osteoblasts under inductive
      conditions in vitro and participated in cartilage and bone formation in vivo.
      Additionally, adipogenic and angiogenic potentials of clonal MECs (cMECs) were
      observed. Overall, our study showed that cMECs not only display typical
      properties of adult stem cells but also exhibit chondrogenic and osteogenic
      capacities in vitro and in vivo, suggesting their potential applications in
      articular cartilage and bone repair/regeneration.

PMID- 23553741
TI  - Bacillus amyloliquefaciens Q-426 as a potential biocontrol agent against Fusarium
      oxysporum f. sp. spinaciae.
AB  - In recent years, Bacillus species have received considerable attention for the
      biological control of many fungal diseases. In this study, Bacillus
      amyloliquefaciens Q-426 was tested for its potential use against a variety of
      plant pathogens. Our screen for genes involved in the biosynthesis of antifungal
      agents revealed that the fen and bmy gene clusters are present in the Q-426
      genome. Lipopeptides such as bacillomycin D, fengycin A, and fengycin B were
      purified from the bacterial culture broth and subsequently identified by ESI-mass
      spectrometry. The minimal inhibitory concentration of fengycin A against Fusarium
      oxysporum f. sp. spinaciae W.C. Snyder & H.N. Hansen O-27 was determined to be
      31.25 MUg ml(-1) . However, exposure of fungal cells to 50 MUg ml(-1) of fengycin
      A did not allow permeation of fluorescein diacetate into the cytoplasm through
      the cell membrane. Moreover, leakage of intracellular inorganic cations, nucleic
      acid and protein were also not detected, indicating that the fungal cell membrane
      is not the primary target of action for fengycin A. Profound morphological
      changes were observed in the F. oxysporum strain and spore germination was
      completely inhibited, suggesting that 50 MUg ml(-1) of fengycin A acts, at least,
      as a fungistatic agent. 

PMID- 23553742
TI  - Structure- and dose-absorption relationships of coffee polyphenols.
AB  - Chlorogenic acids (CGAs) from coffee have biological effects related to human
      health. Thus, specific data on their bioavailability in the upper
      gastrointestinal tract are of high interest, since some molecules are absorbed
      here and so are not metabolized by colonic microflora. Up to now, no data on
      structure-absorption relationships for CGAs have been published, despite this
      being the most consumed group of polyphenols in the western diet. To address this
      gap, we performed ex vivo absorption experiments with pig jejunal mucosa using
      the Ussing chamber model (a model simulating the mucosa and its luminal/apical
      side). The main coffee polyphenols, caffeoylquinic acid (CQA), feruloylquinic
      acid (FQA), caffeic acid (CA), dicaffeoylquinic acid (diCQA), and D-(-)-quinic
      acid (QA), were incubated in individual experiments equivalent to gut lumen
      physiologically achievable concentrations (0.2-3.5 mM). Identification and
      quantification were performed with HPLC-diode array detection and HPLC-MS/MS.
      Additionally, the presence of ABC-efflux transporters was determined by Western
      blot analysis. The percentages of initially applied CGAs that were absorbed
      through the jejunal pig mucosa were, in increasing order: diCQA, trace; CQA, ~
      1%; CA, ~ 1.5%; FQA, ~ 2%; and QA, ~ 4%. No differences were observed within the
      CGA subgroups. Dose-absorption experiments with 5-CQA suggested a passive
      diffusion (nonsaturable absorption and a linear dose-flux relationship) and its
      secretion was affected by NaN3 , indicating an active efflux. The ABC-efflux
      transporters MDR 1 and MRP 2 were identified in pig jejunal mucosa for the first
      time. We conclude that active efflux plays a significant role in CGA
      bioavailability and, further, that the mechanism of CGA absorption in the jejunum
      is governed by their physicochemical properties.

PMID- 23553743
TI  - Impact of a venous thromboembolism prophylaxis "smart order set": Improved
      compliance, fewer events.
AB  - Venous thromboembolism (VTE) affects over 700,000 Americans annually. Prophylaxis
      reduces the risk of VTE by 60% but many patients still do not receive risk
      appropriate VTE prophylaxis. To improve our institution's VTE prophylaxis
      performance, we developed mandatory computerized clinical decision support
      enabled "smart order sets" that required providers to assess VTE risk factors and
      contraindications to pharmacologic prophylaxis. Using provider responses, the
      order set recommends evidence-based risk-appropriate VTE prophylaxis. To study
      the impact of our "smart order set" on prescription of risk-appropriate VTE
      prophylaxis and clinical outcomes, we conducted a retrospective chart review of
      consecutive patients admitted to the Medicine service during one month
      immediately prior to (November 2007) and a single month subsequent to (April
      2010) order set launch. Data collection included patient demographics, VTE risk
      factors, and the use and type of VTE prophylaxis. The pre- and post
      implementation cohorts contained 1,000 and 942 patients, respectively. After
      implementation of the "smart order set", the prescription of risk-appropriate VTE
      prophylaxis increased from 65.6% to 90.1% (P < 0.0001). Orders for any form of
      VTE prophylaxis increased from 76.4% to 95.6% (P < 0.0001). Radiographically
      documented symptomatic VTE within 90 days of hospital discharge declined from
      2.5% to 0.7% (P = 0.002). Preventable harm was completely eliminated (1.1% to 0%,
      P = 0.001) with no difference in major bleeding or all-cause mortality. A VTE
      prophylaxis computerized clinical decision support-enabled "smart order set"
      improved prescription of risk-appropriate VTE prophylaxis, reduced symptomatic
      VTE and eliminated preventable harm from VTE without increasing major bleeding.

PMID- 23553744
TI  - Benjamin Hobson (1816-1873): His work as a medical missionary and influence on
      the practice of medicine and knowledge of anatomy in China and Japan.
AB  - Benjamin Hobson was a British missionary and physician who lived in China for
      twenty years. He founded multiple hospitals in Southern China and used his
      knowledge of Western medicine to educate Chinese doctors. He wrote several
      medical textbooks in Chinese of which the first was the A New Theory of the Body
      (1851). The illustrations from his book were renditions and originals from
      William Cheselden's Anatomical Tables (1730) and Osteographia (1733).The Japanese
      version of Hobson's work appeared in Japan during the bakumatsu period (1853
      1867), when Japan ended its isolationist foreign policy and began opening itself
      to the West. During this time, many books from Europe were translated into
      Chinese to then find their way into Japan. The Chinese anatomy textbook by Hobson
      (Quanti Xinlun) was instrumental in introducing Western anatomic knowledge to the
      Chinese and thereby catalyzing a significant change in the practice of medicine
      in China. A Japanese translation (Zen Tai Shin Ron) of this text published in the
      19th century is reviewed.

PMID- 23553745
TI  - Microbial community structure in fermentation process of Shaoxing rice wine by
      Illumina-based metagenomic sequencing.
AB  - BACKGROUND: To understand the role of the community structure of microbes in the
      environment in the fermentation of Shaoxing rice wine, samples collected from a
      wine factory were subjected to Illumina-based metagenomic sequencing. RESULTS: De
      novo assembly of the sequencing reads allowed the characterisation of more than
      23 thousand microbial genes derived from 1.7 and 1.88 Gbp of sequences from two
      samples fermented for 5 and 30 days respectively. The microbial community
      structure at different fermentation times of Shaoxing rice wine was revealed,
      showing the different roles of the microbiota in the fermentation process of
      Shaoxing rice wine. The gene function of both samples was also studied in the COG
      database, with most genes belonging to category S (function unknown), category E
      (amino acid transport and metabolism) and unclassified group. CONCLUSION: The
      results show that both the microbial community structure and gene function
      composition change greatly at different time points of Shaoxing rice wine
      fermentation.

PMID- 23553746
TI  - A general method to diverse cinnolines and cinnolinium salts.
AB  - Rhodium catalysis: A highly efficient and general method has been established to
      prepare cinnolines, cinnolinium salts, and polycyclic cinnolinium salts through
      the rhodium(III)-catalyzed oxidative C-H activation/cyclization of azo compounds
      with alkynes (see scheme). Key features of this methodology include the
      unprecedented capacity to create both cinnoline and cinnolinium frameworks.

PMID- 23553747
TI  - A Bayesian semiparametric model for bivariate sparse longitudinal data.
AB  - Mixed-effects models have recently become popular for analyzing sparse
      longitudinal data that arise naturally in biological, agricultural and biomedical
      studies. Traditional approaches assume independent residuals over time and
      explain the longitudinal dependence by random effects. However, when bivariate or
      multivariate traits are measured longitudinally, this fundamental assumption is
      likely to be violated because of intertrait dependence over time. We provide a
      more general framework where the dependence of the observations from the same
      subject over time is not assumed to be explained completely by the random effects
      of the model. We propose a novel, mixed model-based approach and estimate the
      error-covariance structure nonparametrically under a generalized linear model
      framework. We use penalized splines to model the general effect of time, and we
      consider a Dirichlet process mixture of normal prior for the random-effects
      distribution. We analyze blood pressure data from the Framingham Heart Study
      where body mass index, gender and time are treated as covariates. We compare our
      method with traditional methods including parametric modeling of the random
      effects and independent residual errors over time. We conduct extensive
      simulation studies to investigate the practical usefulness of the proposed
      method. The current approach is very helpful in analyzing bivariate irregular
      longitudinal traits.

PMID- 23553748
TI  - Periodontal ligament stem cells regulate B lymphocyte function via programmed
      cell death protein 1.
AB  - Periodontal ligament stem cells (PDLSCs) have provided novel cell sources for
      tooth and periodontal tissue regeneration. Allogeneic PDLSCs can reconstruct
      periodontal ligament tissue that has been damaged by periodontal diseases and
      regulate T-cell immunity. However, the effect of PDLSCs on B cells remains
      unknown. Here, we treated periodontitis in a miniature pig model using allogeneic
      PDLSCs and showed a reduction in humoral immunity in the animals. When cocultured
      with normal B cells, human PDLSCs (hPDLSCs) had similar effects as bone marrow
      mesenchymal stem cells in suppressing B cell proliferation, differentiation, and
      migration, while intriguingly, hPDLSCs increased B cell viability by secreting
      interleukin-6. Mechanistically, hPDLSCs suppressed B cell activation through cell
      to-cell contact mostly mediated by programmed cell death protein 1 and programmed
      cell death 1 ligand 1. Our data revealed a previously unrecognized function of
      PDLSCs in regulating humoral immune responses, which may represent a novel
      therapeutic strategy for immune-related disorders.

PMID- 23553749
TI  - Crystallographic analysis of the ENTH domain from yeast epsin Ent2 that induces a
      cell division phenotype.
AB  - Epsins are eukaryotic, endocytic adaptor proteins primarily involved in the early
      steps of clathrin mediated endocytosis. Two epsins exist in Saccharomyces
      cerevisiae, Ent1 and Ent2, with single epsin knockouts being viable, while the
      double knockout is not. These proteins contain a highly conserved Epsin N
      terminal homology (ENTH) domain that is essential for cell viability. In
      addition, overexpression of the ENTH domain of Ent2 (ENTH2) was shown to play a
      role in cell division by interacting with the septin organizing, Cdc42 GTPase
      activating protein, Bem3, leading to increased cytokinesis failure. In contrast,
      overexpression of the ENTH domain of Ent1 (ENTH1) does not affect cytokinesis,
      despite being 75% identical to ENTH2. An ENTH2(N112D, S114E, E118Q) mutant that
      switches residues in loop 7 to those found correspondingly in ENTH1 was incapable
      of inducing the cytokinesis phenotype. In order to better understand the role of
      loop 7 in the ENTH2-induced phenotype at a molecular level, X-ray crystallography
      was used to elucidate the structures of yeast ENTH2(WT) and ENTH2(DEQ). Our
      results indicate that mutations did not affect the conformation of loop 7, but
      rather introduce an increased negative charge on a potential interaction
      interface. Morphological analysis of cells overexpressing ENTH2 loop 7 mutants
      showed that the cytokinesis failure phenotype was abolished by the single mutants
      N112D, E118Q, and to a lesser extent by S114E. Taken together, our results
      indicate that the interaction surface that contains loop 7 and the specific
      nature of these residues are crucial for ENTH2 involvement in cytokinesis. This
      research provides insight into a molecular mechanism by which ENTH2, but not
      ENTH1, overexpression in yeast leads to cell division defects. Structural data of
      WT and mutant ENTH2 domains along with in vivo phenotypic analysis of ENTH2
      overexpressing cells indicate that the biochemical nature of three loop 7
      residues is crucial for its role in cytokinesis.

PMID- 23553750
TI  - 2-Phenylethynyl-butyltellurium attenuates amyloid-beta peptide(25-35)-induced
      learning and memory impairments in mice.
AB  - Our previous study demonstrated that 2-phenylethynyl-butyltellurium (PEBT), an
      organotellurium compound, enhances memory in mice. In this study, the effects of
      PEBT on cognitive impairment induced by Abeta25-35 were assessed by Morris water
      maze and step-down inhibitory avoidance tasks. Mice received a single
      intracerebroventricular injection of Abeta25-35 (3 nmol/3 MUl/per site) and a
      daily oral administration of PEBT (1 mg/kg, for 10 days). PEBT significantly
      improved Abeta-induced learning deficits on the training session in the Morris
      water maze. At the probe trial session, PEBT significantly decreased the escape
      latency and increased the number of crossings in the platform local compared with
      the Abeta-treated group. PEBT significantly improved Abeta-induced memory
      impairment in the step-down inhibitory avoidance task. General locomotor activity
      was similar in all groups. This study showed that PEBT ameliorated the
      impairments of spatial and nonspatial long-term memory evaluated on Morris water
      maze and step-down inhibitory avoidance tasks, respectively. The results suggest
      that PEBT could be considered a candidate for the prevention of memory deficits
      such as those observed in Alzheimer's disease.

PMID- 23553751
TI  - Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary
      disease (Copd); implications for stratified medicine?
AB  - INTRODUCTION: Quadriceps muscle dysfunction is common in COPD. Determining, and,
      if possible, predicting quadriceps phenotype in COPD is important for patient
      stratification for therapeutic trials. METHODS: In biopsies from 114 COPD
      patients and 30 controls, we measured fiber size and proportion and assessed the
      relationship with quadriceps function (strength and endurance), clinical
      phenotype (lung function, physical activity, fat-free mass) and exercise
      performance. In a subset (n = 40) we measured muscle mid-thigh cross-sectional
      area by computed tomography. RESULTS: Normal ranges for fiber proportions and
      fiber cross-sectional area were defined from controls; we found isolated fiber
      shift in 31% of patients, isolated fiber (predominantly type II) atrophy in 20%,
      both shift and atrophy in 25%, and normal fiber parameters in 24%. Clinical
      parameters related poorly to muscle biopsy appearances. CONCLUSIONS: Quadriceps
      morphology is heterogeneous in COPD and cannot be predicted without biopsy,
      underlining the need for biomarkers.

PMID- 23553752
TI  - Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic
      hepatitis B using serum hepatitis B surface antigen levels.
AB  - On-treatment levels of hepatitis B surface antigen (HBsAg) may predict response
      to peginterferon (PEG-IFN) therapy in chronic hepatitis B (CHB), but previously
      proposed prediction rules have shown limited external validity. We analyzed 803
      HBeAg-positive patients treated with PEG-IFN in three global studies with
      available HBsAg measurements. A stopping-rule based on absence of a decline from
      baseline was compared to a prediction-rule that uses HBsAg levels of <1,500 IU/mL
      and >20,000 IU/mL to identify patients with high and low probabilities of
      response. Patients with an HBsAg level <1,500 IU/mL at week 12 achieved response
      (HBeAg loss with HBV DNA <2,000 IU/mL at 6 months posttreatment) in 45%. At week
      12, patients without a decline in HBsAg achieved a response in 14%, compared to
      only 6% of patients with HBsAg >20,000 IU/mL, but performance varied across HBV
      genotype. In patients treated with PEG-IFN monotherapy (n = 465), response rates
      were low in patients with genotypes A or D if there was no decline of HBsAg by
      week 12 (negative predictive value [NPV]: 97%-100%), and in patients with
      genotypes B or C if HBsAg at week 12 was >20,000 IU/mL (NPV: 92%-98%). At week
      24, nearly all patients with HBsAg >20,000 IU/mL failed to achieve a response,
      irrespective of HBV genotype (NPV for response and HBsAg loss 99% and 100%).
      CONCLUSION: HBsAg is a strong predictor of response to PEG-IFN in HBeAg-positive
      CHB. HBV genotype-specific stopping-rules may be considered at week 12, but
      treatment discontinuation is indicated in all patients with HBsAg >20,000 IU/mL
      at week 24, irrespective of HBV genotype.

PMID- 23553753
TI  - The volume of the chorion villosum is associated with the location of the
      umbilical cord in the first trimester.
AB  - AIMS: To clarify whether villous placental volumes in cases with low cord
      insertion (CI) are smaller than those with normal cord insertion. METHODS: A
      prospective cohort study was conducted to evaluate the association between
      location of umbilical CI and placental volume at 11 to 13 weeks' gestation. An
      ultrasound examination was performed to measure the crown-rump length, the
      distance between the histological internal cervical os and the CI site, the
      placental volume, and the uterine arterial blood flow. To standardize the
      distribution of the ultrasonographic measurements, we transformed data by crown
      rump length-weighted linear regression. RESULTS: Six hundred fifty-nine subjects
      were analyzed. Scatter plots showed a slightly positive correlation between the z
      scores of the distance from the CI site to the internal cervical os and villous
      placental volume (r = 0.102, p = 0.009) and a negative correlation between the z
      scores of the villous placental volume and the uterine arterial pulsatility index
      (r = -0.165, p < 0.001) as well as the uterine arterial resistance index (r = 
      0.187, p < 0.001). CONCLUSION: The placental volume was likely to be smaller in
      cases with CI located in the lower uterine segment.

PMID- 23553754
TI  - Systematic review and meta-analysis of laparoscopic versus open colectomy with
      end ileostomy for non-toxic colitis (Br J Surg 2013: 100 : 726-733).

PMID- 23553755
TI  - Evaluation of biodegradable paclitaxel-eluting nanofibre-covered metal stents for
      the treatment of benign cardia stricture in an experimental model.
AB  - BACKGROUND: Benign strictures at the cardia are troublesome for patients and
      often require repeated endoscopic treatments. Paclitaxel can reduce fibrosis.
      This study evaluated a biodegradable paclitaxel-eluting nanofibre-covered metal
      stent for the treatment of benign cardia stricture in vitro and in vivo. METHODS:
      Drug release was investigated in vitro at pH 7.4 and 4.0. Eighty dogs were
      divided randomly into four groups (each n = 20): controls (no stent), bare stent
      (retained for 1 week), and two drug-eluting stent (DES) groups with retention for
      either 1 week (DES-1w) or 4 weeks (DES-4w). Lower oesophageal sphincter pressure
      (LOSP) and 5-min barium height (5-mBH) were assessed before, immediately after
      stent deployment, at 1 week, and 1, 3 and 6 months later. Five dogs in each group
      were killed for histological examination at each follow-up point. RESULTS: Stent
      migration rates were similar (0 bare stent versus 2 DES; P = 0.548). The
      percentage and amount of paclitaxel released in vitro was higher at pH 4.0 than
      at pH 7.4. After 6 months, LOSP and 5-mBH were both improved in the DES-1w (P =
      0.004 and P = 0.049) and DES-4w (both P < 0.001) groups compared with the bare
      stent group, with better relief when the stent was retained for 4 weeks (P =
      0.004 and P = 0.007). The DES was associated with a reduced peak inflammatory
      reaction and less scar formation compared with bare stents, especially when
      inserted for 4 weeks. CONCLUSION: The DES was more effective for the treatment of
      benign cardia stricture than bare stents in a canine model. Retention of the DES
      for 4 weeks led to a better clinical and pathological outcome than 1 week.

PMID- 23553756
TI  - Repeat hepatectomy for recurrent colorectal metastases (Br J Surg 2013; 100: 808
      818).

PMID- 23553757
TI  - Fatty liver disease as a predictor of local recurrence following resection of
      colorectal liver metastases (Br J Surg 2013: 100: 820-826).

PMID- 23553758
TI  - Clinical and psychosocial functioning in adolescents and young adults with
      anorectal malformations and chronic idiopathic constipation.
AB  - BACKGROUND: Faecal incontinence (FI) and constipation occur following corrective
      surgery for anorectal malformations (ARMs) and in children or adults with chronic
      constipation without a structural birth anomaly (chronic idiopathic constipation,
      CIC). Such symptoms may have profound effects on quality of life (QoL). This
      study systematically determined the burden of FI and constipation in these
      patients in adolescence and early adulthood, and their effect on QoL and
      psychosocial functioning in comparison with controls. METHODS: Patients with ARMs
      or CIC were compared with age- and sex-matched controls who had undergone
      appendicectomy more than 1 year previously and had no ongoing gastrointestinal
      symptoms. Constipation and FI were evaluated using validated Knowles-Eccersley
      Scott Symptom (KESS) and Vaizey scores respectively. Standardized QoL and
      psychometric tests were performed in all groups. RESULTS: The study included 49
      patients with ARMs (30 male, aged 11-28 years), 45 with CIC (32 male, aged 11-30
      years) and 39 controls (21 male, aged 11-30 years). The frequency of severe
      constipation among patients with ARMs was approximately half that seen in the CIC
      group (19 of 49 versus 31 of 45); however, frequencies of incontinence were
      similar (22 of 49 versus 21 of 45) (P < 0.001 versus controls for both symptoms).
      Physical and mental well-being were significantly reduced in both ARM and CIC
      groups compared with controls (P = 0.001 and P = 0.015 respectively), with
      generally worse scores among patients with CIC. Both were predicted by
      gastrointestinal symptom burden (P < 0.001). There were no statistically
      significant differences in state or trait psychiatric morbidity between groups.
      CONCLUSION: FI and constipation are major determinants of poor QoL in adolescents
      and young adults with ARMs and in those with CIC.

PMID- 23553759
TI  - The problem of the poor control arm in surgical randomized controlled trials (Br
      J Surg 2013; 100: 172-173).

PMID- 23553760
TI  - Authors' reply: The problem of the poor control arm in surgical randomized
      controlled trials (Br J Surg 2013; 100: 172-173).

PMID- 23553761
TI  - Authors' reply: Randomized clinical trial of glutamine-supplemented versus
      standard parenteral nutrition in infants with surgical gastrointestinal disease
      (Br J Surg 2012; 99: 929-938).

PMID- 23553764
TI  - Notice of retraction.

PMID- 23553762
TI  - Randomized clinical trial of glutamine-supplemented versus standard parenteral
      nutrition in infants with surgical gastrointestinal disease (Br J Surg 2012; 99:
      929-938).

PMID- 23553765
TI  - Notice of retraction.

PMID- 23553766
TI  - Notice of retraction.

PMID- 23553767
TI  - A comparison of bone quality at the distal radius between Asian and white
      adolescents and young adults: an HR-pQCT study.
AB  - Paradoxically, Asians have lower areal bone mineral density (aBMD), but their
      rates of hip and wrist fractures are lower than whites. Therefore, we used high
      resolution pQCT (HR-pQCT) to determine whether differences in bone macrostructure
      and microstructure, BMD, and bone strength at the distal radius were apparent in
      Asian (n = 91, 53 males, 38 females, [mean +/- SD] 17.3 +/- 1.5 years) and white
      (n = 89, 46 males, 43 females, 18.1 +/- 1.8 years) adolescents and young adults.
      HR-pQCT outcomes included total BMD (Tt.BMD), trabecular bone volume fraction
      (BV/TV), and trabecular number (Tb.N), thickness (Tb.Th), and separation (Tb.Sp).
      We used an automated segmentation algorithm to determine total bone area (Tt.Ar),
      and cortical BMD (Ct.BMD), porosity (Ct.Po), and thickness (Ct.Th), and we
      applied finite element (FE) analysis to HR-pQCT scans to estimate bone strength.
      We fit sex-specific multivariable regression models to compare bone outcomes
      between Asians and whites, adjusting for age, age at menarche (girls), lean mass,
      ulnar length, dietary calcium intake, and physical activity. In males, after
      adjusting for covariates, Asians had 11% greater Tt.BMD, 8% greater Ct.BMD, and
      25% lower Ct.Po than whites (p < 0.05). Also, Asians had 9% smaller Tt.Ar and 27%
      greater Ct.Th (p < 0.01). In females, Asians had smaller Tt.Ar than whites (16%,
      p < 0.001), but this difference was not significant after adjusting for
      covariates. Asian females had 5% greater Ct.BMD, 12% greater Ct.Th, and 11% lower
      Tb.Sp than whites after adjusting for covariates (p < 0.05). Estimated bone
      strength did not differ between Asian and white males or females. Our study
      supports the notion of compensatory elements of bone structure that sustain bone
      strength; smaller bones as observed between those of Asian origin compared with
      white origin have, on average, more dense, less porous, and thicker cortices.
      Longitudinal studies are needed to determine whether ethnic differences in bone
      structure exist in childhood, persist into old age, and whether they influence
      fracture risk. 

PMID- 23553768
TI  - Intensity of factor VIII treatment and inhibitor development in children with
      severe hemophilia A: the RODIN study.
AB  - The objective of this study was to examine the association of the intensity of
      treatment, ranging from high-dose intensive factor VIII (FVIII) treatment to
      prophylactic treatment, with the inhibitor incidence among previously untreated
      patients with severe hemophilia A. This cohort study aimed to include consecutive
      patients with a FVIII activity < 0.01 IU/mL, born between 2000 and 2010, and
      observed during their first 75 FVIII exposure days. Intensive FVIII treatment of
      hemorrhages or surgery at the start of treatment was associated with an increased
      inhibitor risk (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI],
      1.3-3.0). High-dose FVIII treatment was associated with a higher inhibitor risk
      than low-dose FVIII treatment (aHR, 2.3; 95% CI, 1.0-4.8). Prophylaxis was only
      associated with a decreased overall inhibitor incidence after 20 exposure days of
      FVIII. The association with prophylaxis was more pronounced in patients with low
      risk F8 genotypes than in patients with high-risk F8 genotypes (aHR, 0.61, 95%
      CI, 0.19-2.0 and aHR, 0.85, 95% CI, 0.51-1.4, respectively). In conclusion, our
      findings suggest that in previously untreated patients with severe hemophilia A,
      high-dosed intensive FVIII treatment increases inhibitor risk and prophylactic
      FVIII treatment decreases inhibitor risk, especially in patients with low-risk F8
      mutations.

PMID- 23553770
TI  - The inhibition of p85alphaPI3KSer83 phosphorylation prevents cell proliferation
      and invasion in prostate cancer cells.
AB  - Phosphoinositide 3-kinase proteins are composed by a catalytic p110 subunit and a
      regulatory p85 subunit. There are three classes of PI3K, named class I-III, on
      the bases of the protein domain constituting and determining their specificity.
      The first one is the best characterized and includes a number of key elements for
      the integration of different cellular signals. Regulatory p85 subunit shares with
      the catalytic p110 subunit, a N-terminal SH3 domain showing homology with the
      protein domain Rho-GTP-ase. After cell stimulation, all class I PI3Ks are
      recruited to the inner face of the plasma membrane, where they generate
      phosphatidylinositol-3,4,5-trisphosphate by direct phosphorylation of
      phosphatidylinositol-4,5-bisphosphate. All pathways trigger the control of
      different phenomena such as cell growth, proliferation, apoptosis, adhesion and
      migration through various downstream effectors. We have previously provided
      direct evidences that a Serine in position 83, adjacent to the N-terminal SH3
      domain of regulatory subunit of PI3K, is a substrate of PKA. The aim of this work
      is to confirm the role of p85alphaPI3KSer83 in regulating cell proliferation,
      migration and invasion in prostate cancer cells LNCaP. To this purpose cells were
      transfected with mutant forms of p85, where Serine was replaced by Alanine, where
      phosphorylation is prevented, or Aspartic Acid, to mimic the phosphorylated
      residue. The findings of this study suggest that identifying a peptide mimicking
      the sequence adjacent to Ser 83 may be used to produce antibodies against this
      residue that can be proposed as usefool tool for prognosis by correlating
      phosphorylation at Ser83 with tumor stage.

PMID- 23553769
TI  - A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency,
      periodic fevers, and developmental delay (SIFD).
AB  - Congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited
      disorders identified by pathological erythroid precursors with perinuclear
      mitochondrial iron deposition in bone marrow. An international collaborative
      group of physicians and laboratory scientists collated clinical information on
      cases of CSA lacking known causative mutations, identifying a clinical subgroup
      of CSA associated with B immunodeficiency, periodic fevers, and development
      delay. Twelve cases from 10 families were identified. Median age at presentation
      was 2 months. Anemia at diagnosis was sideroblastic, typically severe (median
      hemoglobin, 7.1 g/dL) and markedly microcytic (median mean corpuscular volume,
      62.0 fL). Clinical course involved recurrent febrile illness and gastrointestinal
      disturbance, lacking an infective cause. Investigation revealed B-cell
      lymphopenia (CD19+ range, 0.016-0.22 * 109/L) and panhypogammaglobulinemia in
      most cases. Children displayed developmental delay alongside variable
      neurodegeneration, seizures, cerebellar abnormalities, sensorineural deafness,
      and other multisystem features. Most required regular blood transfusion, iron
      chelation, and intravenous immunoglobulin replacement. Median survival was 48
      months, with 7 deaths caused by cardiac or multiorgan failure. One child
      underwent bone marrow transplantation aged 9 months, with apparent cure of the
      hematologic and immunologic manifestations. We describe and define a novel CSA
      and B-cell immunodeficiency syndrome with additional features resembling a
      mitochondrial cytopathy. The molecular etiology is under investigation.

PMID- 23553771
TI  - Autologous uncultured bone marrow-derived mononuclear cells and modified
      cannulated screw in repair of femoral neck fracture.
AB  - The purpose of this study was to assess whether autologous uncultured bone marrow
      derived mononuclear cells (BMMNCs) combined with modified cannulated screw would
      accelerate the healing of canine femoral neck fracture. BMMNCs were encapsulated
      within fibrin glue (FG) and implanted into the fractured femoral neck via
      modified cannulated screw in experiment group, and the control group was treated
      by modified cannulated screw. Gross observation, radiological examination,
      histological analysis, and blood vessel microdensity counting were used to
      compare bone healing of each group at 1, 2, and 3 months. FG was confirmed as an
      ideal cell-delivery vehicle for BMMNCs proliferation and differentiation in vitro
      testing. In vivo animal testing, faster new bone formation and fracture healing
      were confirmed by gross observation, radiological examination, histological
      analysis in experimental group than in control group at all times points. The
      blood vessel microdensity counting increased gradually both in the experimental
      group and control group, but was more obviously in experimental group at 3 months
      (p < 0.01). These data suggest that autologous BMMNCs combined with modified
      cannulated screw treatment is an effective therapy for femoral neck fracture and
      thus, may be an option for clinical applications.

PMID- 23553772
TI  - High mobility field-effect transistors with versatile processing from a small
      molecule organic semiconductor.
AB  - Trialkylgermyl functionalization allows the development of high-performance
      soluble small-molecule organic semiconductors with mobilities greater than 5
      cm(2) V(-1) s(-1) . Spray-deposited organic thin-film transistors show a record
      mobility of 2.2 cm(2) V(-1) s(-1) and demonstrate the potential for incorporation
      in large-area, low-cost electronic applications.

PMID- 23553773
TI  - Fenestration and duplication of the vertebral artery: the anatomical and clinical
      points of view.
AB  - The vertebral artery (VA) acts as a foundation for the posterior circulation of
      the head and neck. It presents a number of anomalies that can be easily
      visualized thanks to modern imaging techniques, such as MR and CT angiography or
      color Doppler ulrasonography. Determining the appropriate terminology for those
      anomalies can be sometimes more challenging than their recognition. One
      particular challenge concerns the differentiation between VA fenestration and
      duplication. Because of the different clinical prognoses associated with those
      anomalies, confusion should be avoided. Knowledge of the morphological anomalies
      associated with the VA is important for both radiologists and head and neck
      surgeons, because any injury to the VA can result in a threat to the vascular
      supply of the brain stem, the cerebral or cerebellar hemispheres, the thalamus,
      cervical nerve roots and particularly the lateral medulla (Wallenberg's
      syndrome). This article analyses world literature concerning the issue of VA
      fenestration and duplication to facilitate a differential diagnosis.

PMID- 23553774
TI  - Effect of alternative postharvest control treatments on the storability of
      'Golden Delicious' apples.
AB  - BACKGROUND: Apples are subject to a high degree of fungal diseases, but the use
      of synthetic fungicides has been questioned because of public safety concerns,
      social rejection, and the development of resistance in pathogens. Thus,
      development of new postharvest treatments against apple fungal pathogens is
      necessary. Most studies have reported their effectiveness, but not all report the
      effects on the quality and storability of the fruit. In this study, the effects
      of physical (hot water), chemical (quercetin) and biological (yeast antagonist)
      microfungal control on the quality of 'Golden Delicious' apple during storage at
      2 +/- 0.5  degrees C, and 90 +/- 2% of relative humidity, for 2 months were
      investigated and compared. RESULTS: Heat-treated apples exhibited peel fruit
      damage (surface browning and internal breakdown disorders) and promoted ripening
      in the fruit. The quercetin caustic spray caused the development of peel chemical
      burn in all treated fruit. Both yeast antagonist and quercetin treatments did not
      affect the apple ripening process but stimulated an increase in ethylene
      production and in respiratory activity. CONCLUSION: The data indicated that the
      effects on quality and storability were dependent on the method of treatment
      used, and antagonistic yeast was the best microfungal control because of it did
      not cause any disorders or negative effects on apple quality during storage.

PMID- 23553775
TI  - In vitro evaluation of nematophagous activity of fungal isolates.
AB  - Four filamentous fungi associated with nematodes were isolated and identified
      from litter samples collected in the Integral Natural Reserve "Bosco Siro Negri"
      (PV, Italy): Arthrobotrys dactyloides, Arthrobotrys oligospora var. oligospora,
      Pochonia bulbillosa, and Pochonia chlamydosporia var. catenulata. Their capacity
      to break down the nematode population was evaluated in vitro by means of simple
      and reproducible multiwell plates method. All fungal strains were able to cause a
      death-rate significantly different from the controls (p < 0.05). Precisely, A.
      dactyloides caused, on average, a 26% death rate increase in the nematode
      population compared to the control, A. oligospora var. oligospora 25%, P.
      bulbillosa 12%, and P. chlamidosporia var. catenulata 17%. The method has also
      allowed to determine the more active fungi as regards the prey's life cycle
      stage. The most active strains against nematodes (adults) were A. dactyloides and
      A. oligospora var. oligospora, known to attack adults or larval stages by means
      of tridimensional traps. On the contrary P. bulbillosa and P. chlamydosporia,
      known to attack mainly the nematode life stage of cysts, showed lower activity
      against adult nematodes.

PMID- 23553776
TI  - B-cell-directed therapies in systemic lupus erythematosus--where do we stand?

PMID- 23553777
TI  - B cell biology: implications for treatment of systemic lupus erythematosus.
AB  - B cells are critical players in the orchestration of properly regulated immune
      responses, normally providing protective immunity without autoimmunity. Balance
      in the B cell compartment is achieved through the finely regulated participation
      of multiple B cell populations with different antibody-dependent and independent
      functions. Both types of functions allow B cells to modulate other components of
      the innate and adaptive immune system. Autoantibody-independent B cell functions
      include antigen presentation, T cell activation and polarization, and dendritic
      cell modulation. Several of these functions are mediated by the ability of B
      cells to produce immunoregulatory cytokines and chemokines and by their critical
      contribution to lymphoid tissue development and organization including the
      development of ectopic tertiary lymphoid tissue. Additionally, the functional
      versatility of B cells enables them to play either protective or pathogenic roles
      in autoimmunity. In turn, B cell dysfunction has been critically implicated in
      the pathophysiology of systemic lupus erythematosus (SLE), a complex disease
      characterized by the production of autoantibodies and heterogeneous clinical
      involvement. Thus, the breakdown of B cell tolerance is a defining and early
      event in the disease process and may occur by multiple pathways, including
      alterations in factors that affect B cell activation thresholds, B cell
      longevity, and apoptotic cell processing. Once tolerance is broken,
      autoantibodies contribute to autoimmunity by multiple mechanisms including immune
      complex mediated Type III hypersensitivity reactions, type II antibody-dependent
      cytotoxicity, and by instructing innate immune cells to produce pathogenic
      cytokines including IFNalpha, TNF and IL-1. The complexity of B cell functions
      has been highlighted by the variable success of B cell-targeted therapies in
      multiple autoimmune diseases, including those conventionally viewed as T cell
      mediated conditions. Given the widespread utilization of B cell depletion therapy
      in autoimmune diseases and the need for new therapeutic approaches in SLE, a
      better understanding of human B cell subsets and the balance of pathogenic and
      regulatory functions is of the essence.

PMID- 23553778
TI  - The role of B lymphocyte stimulator in B cell biology: implications for the
      treatment of lupus.
AB  - B lymphocyte stimulator (BLyS; also known as B cell activating factor (BAFF))
      plays a key role in peripheral B cell tolerance. Mounting evidence indicates that
      B cell tolerance can be either broken or modulated by deliberately manipulating
      BLyS levels, and belimumab, a BLyS-neutralizing antibody, was recently approved
      for the treatment of systemic lupus erythematosus (SLE). Thus, intense
      investigation has focused on understanding how therapeutics targeting BLyS may
      work, and accumulating evidence suggests multiple points of action. BLyS
      signaling, in conjunction with B cell receptor (BCR) signaling, determines the
      size and quality of the mature primary B cell compartment. Moreover, BLyS family
      members play roles in antigen-experienced B cell selection and differentiation.
      Together, these findings have implications for the continued development of novel
      therapeutics that target BLyS.

PMID- 23553779
TI  - Breaking the ice in systemic lupus erythematosus: belimumab, a promising new
      therapy.
AB  - B lymphocyte stimulator (BLyS), a protein discovered in the 1990s that induces B
      cell proliferation and differentiation, promotes B cell survival, and is
      important in immunoglobulin class switching, was the target of a drug development
      program launched by Human Genome Sciences in the early part of the last decade.
      Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately
      approved by the United States Food and Drug Administration (FDA) in March 2011
      for active autoantibody patients with systemic lupus erythematosus (SLE) despite
      standard therapy. This program, whose studies spanned approximately 10 years from
      phase I through phase III, was founded on sound biology and advanced on logic and
      perseverance. Pre-clinical experimentation in murine models of SLE as well as
      observational studies in human SLE provided sufficient evidence to support the
      use of an inhibitor of BLyS as a novel therapy to reduce SLE disease activity.
      Progressing from phase I through a robust phase III program was no easy task
      given the complexities of SLE trial design. These challenges were overcome with
      the implementation of strict study entry requirements, the development of a novel
      responder index, and rigorous rules regarding background therapies. The success
      of two phase III studies and the approval of belimumab by the US Food and Drug
      Administration represent an unprecedented milestone in the history of SLE drug
      development. Belimumab was the first drug approved in SLE in over 50 years and
      was the first drug ever approved in SLE through the conventional route of
      randomized controlled trials. This article reviews the biology of BLyS, clinical
      trial results, and some of the emerging data from the robust phase II and III
      datasets.

PMID- 23553780
TI  - Belimumab for systemic lupus erythematosus: a practice-based view.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with multiple
      organ involvement. B-lymphocyte activity plays a pivotal role in the development
      and course of the disease. A newly developed agent called belimumab has recently
      been approved to treat active, autoantibody positive SLE as an add-on to standard
      therapy. Specifically binding to soluble B-lymphocyte stimulator protein, it
      reduces the formation of immunoglobulins and autoantibodies. Its effects have
      been studied in one phase II and two phase III clinical trials, showing sustained
      improvement across various clinical indicators and no evidence of increased risk
      of serious adverse events. Further post-hoc analyses indicate that treatment with
      belimumab lowers levels of autoimmune antibodies, normalizes low complement and
      improves SLE activity predominantly in musculoskeletal and mucocutaneous organ
      domains. Further studies are needed to determine the efficacy of belimumab for
      patients with severe lupus nephritis and with active involvement of the central
      nervous system. The introduction of belimumab as the first biological drug
      approved for the management of SLE likely heralds a surge in the development and
      use of selectively addressed agents for this heterogeneous and complex disease.

PMID- 23553781
TI  - Rituximab treatment in lupus nephritis--where do we stand?
AB  - Renal involvement in systemic lupus erythematosus (SLE) is a severe disease
      manifestation in which novel therapeutic strategies are needed, especially in non
      responding patients or patients who relapse after conventional treatment.
      Rituximab has been used as off-label treatment for lupus nephritis (LN) during
      the last decade, and to date reports on the clinical effects on more than 400
      patients, including the randomized controlled LUNAR study population, have been
      published. Despite promising results obtained from observational studies and
      registries, with complete or partial renal response after 6-12 months in 67-77%
      of patients, the LUNAR trial failed to attain the primary endpoint and rituximab
      is today unlikely to be approved as treatment for LN. Rituximab has mainly been
      used as induction therapy in combination with standard of care but the optimal
      treatment protocol is still to be determined. From observational studies,
      rituximab has been shown to be efficient in both proliferative and membranous LN,
      and histopathological studies have demonstrated improvement in renal activity.
      Adverse events mainly include infusion reactions and infections. Although not
      approved for the treatment of LN, the currently available data support that
      rituximab may be used in severe, refractory cases of LN.

PMID- 23553782
TI  - Minimising steroids in lupus nephritis--will B cell depletion pave the way?
AB  - The aim of this review is to briefly explore how steroids came to be a presumed
      adjunct to all treatment regimens for lupus nephritis, despite being the main
      cause of long term damage among patients with lupus and despite increasingly
      effective alternative agents. I then go on to compare and contrast how
      differently immunosuppression regimens have developed in the world of solid organ
      transplantation. Almost from the start of transplantation a clear goal was to
      develop steroid sparing regimens - and now units such as our own routinely use
      induction with a biological, a single week of steroids and then monotherapy with
      tacrolimus. There has been a clear trend of using biologicals as induction agents
      and less immunosuppression in the long run but with improved outcomes. The drive
      has not been the same in lupus nephritis despite there being almost no evidence
      to support the use of steroids and certainly nothing to suggest correct dosage
      and timing. Rituximab, a B cell depleting antibody, offers great promise as a
      treatment agent despite the negative randomised control LUNAR trial. I briefly
      review our own data, demonstrating that early use of rituximab in lupus nephritis
      allows omission of oral steroids with excellent rates of remission (complete and
      partial). I review why the LUNAR trial should not discourage the use of
      rituximab. Finally, I introduce the RITUXILUP trial, a multicentre randomised
      controlled trial we are developing to formally evaluate our oral steroid avoiding
      regimen against a standard treatment regimen of mycophenolate mofetil and
      steroids. We have to follow the lead of our transplant colleagues and challenge
      the assumption that the future for lupus nephritis cannot be steroid free.

PMID- 23553783
TI  - Epratuzumab for systemic lupus erythematosus.
AB  - Epratuzumab (EMab, UCB, Immunomedics) is a humanized monoclonal antibody
      targeting CD22 that is being studied in clinical trials for patients with a
      variety of rheumatic and hematologic conditions, including systemic lupus
      erythematosus (SLE). An overview of its mechanism of action is followed by a
      summary of completed lupus studies, and a preview of studies in progress. The
      agent clearly has anti-inflammatory activity and is a potentially useful agent in
      the management of autoimmune disorders.

PMID- 23553784
TI  - MRI-based prediction of pulsed high-intensity focused ultrasound effect on tissue
      transport in rabbit muscle.
AB  - PURPOSE: To design an algorithm for optimizing pulsed high intensity focused
      ultrasound (p-HIFU) treatment parameters to maximize tissue transport while
      minimizing thermal necrosis based on MR image guidance. MATERIALS AND METHODS: P
      HIFU power, duty cycle, and treatment duration were varied to generate different
      levels of thermal and mechanical deposition in rabbit muscle. Changes in T2
      weighted and T1 contrast-enhanced (CE) signal were assessed immediately following
      treatment and at 24 h. Transport parameters were extracted by means of T1
      weighted dynamic contrast-enhanced MRI (DCE-MRI) technique at 0 and 24-h time
      points. RESULTS: Successful p-HIFU treatment was indicated by focal
      hyperintensity on the T2-weighted image immediately post-treatment, suggesting
      increased fluid (edema), with little intensity change in CE image. After 24 h,
      the affected region expanded along the muscle fiber accompanied by clear
      hyperintensity in CE image (contrast uptake). Quantitative DCE-MRI analysis
      revealed statistically significant increases in both leakage rate and
      extracellular space, accompanied by a decrease in clearance rate. CONCLUSION:
      Successful p-HIFU treatment was mainly correlated to tissue heating. Tissue
      transport properties following treatment success would result in improved contact
      between drug and targets in both time and space. MRI is the key to controlling
      treatment by means of thermometry and also monitoring efficacy by means of T2
      weighted imaging.

PMID- 23553785
TI  - A comparison of Bayesian hierarchical modeling with group-based exposure
      assessment in occupational epidemiology.
AB  - We build a Bayesian hierarchical model for relating disease to a potentially
      harmful exposure, by using data from studies in occupational epidemiology, and
      compare our method with the traditional group-based exposure assessment method
      through simulation studies, a real data application, and theoretical calculation.
      We focus on cohort studies where a logistic disease model is appropriate and
      where group means can be treated as fixed effects. The results show a variety of
      advantages of the fully Bayesian approach and provide recommendations on
      situations where the traditional group-based exposure assessment method may not
      be suitable to use.

PMID- 23553786
TI  - Supplementation with apple enriched with L-arginine may improve metabolic control
      and survival rate in alloxan-induced diabetic rats.
AB  - Supplementation with L-arginine or fresh food with high content of this amino
      acid is associated with favorable effects in the metabolic control of diabetes.
      We aimed to determine whether supplementation with apples enriched with L
      arginine offer additional benefits compared to L-arginine by itself in a
      preclinical study of diabetes. This study combines food-engineer technologies
      with in vivo and in vitro analysis. In vitro experiments show that cells derived
      from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells
      isolated from alloxan-induced diabetic animals exhibited a reduction (~50%) in
      the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H)
      in both the normal and diabetes-derived cells. In preclinical studies,
      normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups
      that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L
      arginine or vehicle (control). In a preliminary analysis, supplementation with L
      arginine by itself (50%) or apple enriched with L-arginine (100%) improve
      survival rate in the diabetic group compared to control (0%) at the end of the
      follow up (17 days). This phenomenon was associated with a partial but sustained
      high plasma level of L-arginine, as well as plasma concentration of nitrites and
      insulin in the L-arginine or apple + L-arginine groups after supplementation.
      Apple + L-arginine supplementation in diabetic animals induced the highest and
      longest effects in the level of these three markers among the studied groups.
      Therefore, apple enriched by L-arginine offers more benefits than L-arginine by
      itself in this preclinical study.

PMID- 23553787
TI  - RyR1 deficiency in congenital myopathies disrupts excitation-contraction
      coupling.
AB  - In skeletal muscle, excitation-contraction (EC) coupling is the process whereby
      the voltage-gated dihydropyridine receptor (DHPR) located on the transverse
      tubules activates calcium release from the sarcoplasmic reticulum by activating
      ryanodine receptor (RyR1) Ca(2+) channels located on the terminal cisternae. This
      subcellular membrane specialization is necessary for proper intracellular
      signaling and any alterations in its architecture may lead to neuromuscular
      disorders. In this study, we present evidence that patients with recessive RYR1
      related congenital myopathies due to primary RyR1 deficiency also exhibit
      downregulation of the alfa 1 subunit of the DHPR and show disruption of the
      spatial organization of the EC coupling machinery. We created a cellular RyR1
      knockdown model using immortalized human myoblasts transfected with RyR1 siRNA
      and confirm that knocking down RyR1 concomitantly downregulates not only the DHPR
      but also the expression of other proteins involved in EC coupling. Unexpectedly,
      this was paralleled by the upregulation of inositol-1,4,5-triphosphate receptors;
      functionally however, upregulation of the latter Ca(2+) channels did not
      compensate for the lack of RyR1-mediated Ca(2+) release. These results indicate
      that in some patients, RyR1 deficiency concomitantly alters the expression
      pattern of several proteins involved in calcium homeostasis and that this may
      influence the manifestation of these diseases.

PMID- 23553788
TI  - Protein kinase CK2 enhances Mcl-1 gene expression through the serum response
      factor-mediated pathway in the rat hippocampus.
AB  - The protein kinase CK2 (casein kinase 2) is a ubiquitous serine/threonine protein
      kinase that suppresses apoptosis. CK2 is composed of catalytic and regulatory
      subunits, and CK2-dependent phosphorylation is a global mechanism in the
      inhibition of caspase signaling pathways. The serum response factor (SRF) is an
      important regulator of cell growth and differentiation. Although CK2 has been
      shown to phosphorylate SRF in vitro, the biological relevance of this interaction
      remains largely unclear. We observed increased SRF phosphorylation and increased
      Mcl-1 gene expression in hippocampal CA1 neurons following transfection with a
      plasmid expressing the wild-type CK2alpha (CK2alphaWT) protein, whereas
      transfection with a plasmid expressing a catalytically inactive mutant of
      CK2alpha (CK2alpha156A) reduced Mcl-1 gene expression. Cotransfection with a
      plasmid expressing the inactive SRF99A mutant inhibited the CK2alphaWT-induced
      upregulation of Mcl-1 gene expression. The expression of either the CK2alpha156A
      or the SRF99A mutant also inhibited the glutamate-induced upregulation of Mcl-1
      protein expression in PC12 cells. Our results suggest that CK2-mediated signaling
      represents a cellular mechanism that may aid in the development of alternative
      therapeutic strategies to attenuate apoptosis in hippocampal neurons.

PMID- 23553789
TI  - Feeding ecology of red langurs in Sabangau tropical peat-swamp forest, Indonesian
      Borneo: extreme granivory in a non-masting forest.
AB  - Southeast Asia's lowland dipterocarp forests experience supra-annual "mast"
      fruiting and flowering events, in which the majority of trees reproduce
      simultaneously at irregular intervals, with extensive intervening periods of very
      low primate food availability. This scarcity of food results in a negative energy
      balance and a reliance on "fallback foods" in some primate species. By contrast,
      ombrogenous tropical peat-swamp forests are non-masting, and show lower
      variability of food availability. We sought to test the influence of fruit
      availability on primate diet and preference in peat-swamp habitats and assess
      whether it differs from masting forests. We collected behavioral-dependent
      feeding data on three adult females in a group of red langurs (Presbytis
      rubicunda: Colobinae) between January and December 2011 in Sabangau tropical peat
      swamp forest, Central Kalimantan, Indonesia, as colobine monkeys are adaptated
      for folivory, and are therefore generally considered less reliant on temporally
      variable fruits than monogastric primates. We documented the highest level of
      granivory recorded to date in colobine monkeys: mean annual diet comprised 76.4%
      seeds and 7.3% other fruit parts; 7.7% young and 2.5% mature leaves; 2.8%
      flowers; 2.6% piths, and <1% on other minor food items. Fruit availability was
      fairly constant throughout the year and fruit parts were consumed at consistently
      higher levels than expected based on availability, confirming that fruit is
      preferred. Leaves and flowers were consumed consistently less than expected and
      thus are not preferred. There were no significant correlations between preferred
      food availability and consumption of potential fallback foods, suggesting that
      reliance on fallback foods did not occur in Sabangau during the study period.
      Furthermore, consumption of fruit was not significantly correlated with its
      availability. Our findings suggest that the relatively constant availability of
      fruit in this habitat affords P. rubicunda regular access to a nutritionally
      superior food, and that reliance on fallback foods is therefore not required.

PMID- 23553790
TI  - Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind,
      placebo-controlled phase III trial.
AB  - OBJECTIVE: To compare the efficacy of tanezumab versus placebo for reducing pain
      and improving physical function in patients with osteoarthritis (OA) of the hip.
      METHODS: This was a 32-week, randomized, double-blind, placebo-controlled, phase
      III trial. Patients with baseline Western Ontario and McMaster Universities OA
      Index (WOMAC) Pain and Physical Function subscale scores of >=5 and >=4,
      respectively, and patient's global assessment of OA as "fair," "poor," or "very
      poor" were treated at baseline and weeks 8 and 16. Coprimary efficacy end points
      were change from baseline to week 16 in WOMAC Pain and Physical Function
      subscales and patient's global assessment, analyzed using analysis of covariance.
      Adverse events (AEs) were monitored throughout. RESULTS: Patients (n = 621) were
      randomized 1:1:1:1 to treatment with intravenous tanezumab 2.5 mg, 5 mg, or 10 mg
      or placebo. Each tanezumab group showed significant improvement for the 3
      coprimary end points versus placebo (P <= 0.001 for all). AE incidence ranged
      from 55% to 58% across tanezumab groups versus 44% for placebo. Safety findings
      were similar to those previously reported. The tanezumab OA clinical program was
      temporarily placed on hold because of AEs leading to joint replacement. Total
      joint replacements were reported in 8 patients: 1 in the 10 mg, 2 in the 5 mg, 2
      in the 2.5 mg, and 3 in the placebo group. A total of 9 joints were replaced (8
      hips [7 index joints] and 1 shoulder). CONCLUSION: Our findings indicate that
      tanezumab provides superior pain relief and improvement in physical function and
      patient's global assessment versus placebo in patients with painful hip OA, and
      is generally well tolerated.

PMID- 23553792
TI  - Hybrid hydrogels of porous graphene and nickel hydroxide as advanced
      supercapacitor materials.
AB  - Graphene-based hydrogels can be used as supercapacitor electrodes because of
      their excellent conductivity, their large surface area and their high
      compatibility with electrolytes. Nevertheless, the large aspect ratio of graphene
      sheets limits the kinetics of processes occurring in the electrode of
      supercapacitors. In this study, we have introduced in-plane and out-of-plane
      pores into a graphene-nickel hydroxide (Ni(OH)2) hybrid hydrogel, which
      facilitates charge and ion transport in the electrode. Due to its optimised
      chemistry and architecture, the hybrid electrode demonstrates excellent
      electrochemical properties with a combination of high charge storage capacitance,
      fast rate capability and stable cycling performance. Remarkably, the Ni(OH)2 in
      the hybrid contributes a capacitance as high as 3138.5 F g(-1), which is
      comparable to its theoretical capacitance, suggesting that such structure
      facilitates effectively charge-transfer reactions in electrodes. This work
      provides a facile pathway for tailoring the porosity of graphene-based materials
      for improved performances. Moreover, this work has also furthered our
      understanding in the effect of pore and hydrogel structures on the
      electrochemical properties of materials.

PMID- 23553791
TI  - IFN-gamma and TNF-alpha synergistically induce mesenchymal stem cell impairment
      and tumorigenesis via NFkappaB signaling.
AB  - An inflammatory microenvironment may cause organ degenerative diseases and
      malignant tumors. However, the precise mechanisms of inflammation-induced
      diseases are not fully understood. Here, we show that the proinflammatory
      cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF
      alpha) synergistically impair self-renewal and differentiation of mesenchymal
      stem cells (MSCs) via nuclear factor kappaB (NFkappaB)-mediated activation of
      mothers against decapentaplegic homolog 7 (SMAD7) in ovariectomized (OVX) mice.
      More interestingly, a long-term elevated levels of IFN-gamma and TNF-alpha result
      in significantly increased susceptibility to malignant transformation in MSCs
      through NFkappaB-mediated upregulation of the oncogenes c-Fos and c-Myc.
      Depletion of either IFN-gamma or TNF-alpha in OVX mice abolishes MSC impairment
      and the tendency toward malignant transformation with no NFkappaB-mediated
      oncogene activation. Systemic administration of aspirin, which significantly
      reduces the levels of IFN-gamma and TNF-alpha, results in blockage of MSC
      deficiency and tumorigenesis by inhibition of NFkappaB/SMAD7 and NFkappaB/c-FOS
      and c-MYC pathways in OVX mice. In summary, this study reveals that inflammation
      factors, such as IFN-gamma and TNF-alpha, synergistically induce MSC deficiency
      via NFkappaB/SMAD7 signaling and tumorigenesis via NFkappaB-mediated oncogene
      activation.

PMID- 23553793
TI  - Peptidyl cyclopropenones: reversible inhibitors, irreversible inhibitors, or
      substrates of cysteine proteases?
AB  - Peptidyl cyclopropenones were previously introduced as selective cysteine
      protease reversible inhibitors. In the present study we synthesized one such
      peptidyl cyclopropenone and investigated its interaction with papain, a prototype
      cysteine protease. A set of kinetics, biochemical, HPLC, MS, and (13)C-NMR
      experiments revealed that the peptidyl cyclopropenone was an irreversible
      inhibitor of the enzyme, alkylating the catalytic cysteine. In parallel, this
      cyclopropenone also behaved as an alternative substrate of the enzyme, providing
      a product that was tentatively suggested to be either a spiroepoxy cyclopropanone
      or a gamma-lactone. Thus, a single family of compounds exhibits an unusual
      variety of activities, being reversible inhibitors, irreversible inhibitors and
      alternative substrates towards enzymes of the same family.

PMID- 23553794
TI  - Relationship between the umbilical cord coiling index and the umbilical blood
      flow at 11-13 weeks of gestation.
AB  - OBJECTIVES: The aim of this study was to clarify the effects of umbilical cord
      coiling on the umbilical blood flow at 11-13 weeks of gestation. METHODS: A cross
      sectional study was conducted among consecutive pregnant females at 11-13 weeks
      of gestation. Transabdominal ultrasound examinations were performed to obtain the
      umbilical coiling index (CI), the maximum umbilical arterial peak velocity at the
      free loop, the venous velocities at the free loop and the umbilical ring, and the
      umbilical arterial and venous flow volumes. After every measurement was
      standardized according to the crown-rump length (CRL), correlations between the
      CI and these measurements were analyzed. RESULTS: A total of 364 subjects were
      enrolled. The CI significantly decreased in association with advancing gestation.
      There were significant correlations between the CRLs and the umbilical arterial
      peak velocities, the venous velocities at the free loop and the umbilical ring,
      and the umbilical arterial and venous flow volumes. The z-scores of the umbilical
      arterial and venous velocimetries exhibited no significant correlations with the
      CI. The umbilical arterial and venous flow volumes were also not found to
      correlate with the CI. CONCLUSIONS: The CI does not affect either the umbilical
      arterial or venous blood flow at 11-13 weeks of gestation.

PMID- 23553795
TI  - Utility of skin biopsy in management of small fiber neuropathy.
AB  - INTRODUCTION: We examined the role of skin biopsy in the evaluation and
      management of patients with suspected small fiber neuropathy (SFN). METHODS: A
      retrospective chart review was performed among all patients who underwent skin
      biopsy for evaluation of SFN at our institution between March 2008 and March
      2011. Change in management was defined as a new diagnosis or change in treatment
      in response to both positive and negative skin biopsies. RESULTS: Among 69
      patients who underwent skin biopsy, 25 had pathological evidence of an SFN, and 9
      had evidence of borderline SFN. Change in management or diagnosis occurred in 14
      of 25 patients with definite SFN, 6 of 9 patients with borderline SFN, and 16 of
      35 biopsy negative patients. CONCLUSIONS: Skin biopsy changed management or
      diagnosis in 52% of patients evaluated for a possible SFN and appears to play a
      valuable role in the workup of these patients.

PMID- 23553796
TI  - Impaired postoperative leucocyte counts after preoperative radiotherapy for
      rectal cancer in the Stockholm III Trial.
AB  - BACKGROUND: Radiotherapy (RT) in rectal cancer increases postoperative morbidity.
      A suggested reason is RT-induced bone marrow depression resulting in impaired
      leucocyte counts. The ongoing Stockholm III Trial randomizes patients with
      operable rectal cancers to short-course RT with immediate surgery (SRT), short
      course RT with surgery delayed for 4-8 weeks (SRT-delay) and long-course RT with
      surgery delayed for 4-8 weeks (LRT-delay). This study examined differences
      between the randomization arms regarding leucocyte response and postoperative
      complications. METHODS: Patients randomized in the Stockholm III Trial between
      October 1998 and November 2010 were included. Data were collected in a
      prospective register. Additional data were obtained by retrospective review of
      clinical records. RESULTS: Of 657 randomized patients, 585 had data on
      leucocytes. The SRT arm had the highest proportion of postoperative complications
      (SRT, 52.5 per cent; SRT-delay, 39.4 per cent; LRT-delay, 41 per cent; P =
      0.010). There was no association between low preoperative leucocyte count and
      postoperative complications (P = 0.238). Irrespective of randomization arm,
      patients with an impaired postoperative to preoperative leucocyte ratio had the
      highest rate of complications (low ratio, 56.6 per cent; intermediate ratio, 46.9
      per cent; high ratio, 36.3 per cent; P = 0.010). The SRT arm had the highest
      proportion of low ratios (SRT, 48.9 per cent; SRT-delay, 22.8 per cent; LRT
      delay, 22 per cent; P < 0.001). CONCLUSION: An impaired postoperative leucocyte
      response is associated with postoperative complications. The highest risk is with
      immediate surgery following short-course radiotherapy. REGISTRATION NUMBER: NCT
      00904813 (http://www.clinicaltrials.gov).

PMID- 23553797
TI  - Bone remodeling is regulated by inner ear vestibular signals.
AB  - Bone remodeling allows the conservation of normal bone mass despite constant
      changes in internal and external environments. The adaptation of the skeleton to
      these various stimuli leads credence to the notion that bone remodeling is a true
      homeostatic function, and as such is under the control of specific centers in the
      central nervous system (CNS). Hypothalamic and brainstem centers, as well as the
      sympathetic nervous system (SNS), have been identified as regulators of bone
      remodeling. However, the nature of the afferent CNS stimuli that may modulate CNS
      centers involved in the control of bone remodeling, with the exception of leptin,
      remains unclear. Based on the partial efficacy of exercise and mechanical
      stimulation regimens to prevent microgravity-induced bone loss and the known
      alterations in vestibular functions associated with space flights, we
      hypothesized that inner ear vestibular signals may contribute to the regulation
      of bone remodeling. Using an established model of bilateral vestibular lesions
      and microtomographic and histomorphometric bone analyses, we show here that
      induction of bilateral vestibular lesion in rats generates significant bone loss,
      which is restricted to weight-bearing bones and associated with a significant
      reduction in bone formation, as observed in rats under microgravity conditions.
      Importantly, this bone loss was not associated with reduced locomotor activity or
      metabolic abnormalities, was accompanied with molecular signs of increased
      sympathetic outflow, and could be prevented by the beta-blocker propranolol.
      Collectively, these data suggest that the homeostatic process of bone remodeling
      has a vestibulosympathetic regulatory component and that vestibular system
      pathologies might be accompanied by bone fragility.

PMID- 23553798
TI  - Relationship between fermentation index and other biochemical changes evaluated
      during the fermentation of Mexican cocoa (Theobroma cacao) beans.
AB  - BACKGROUND: During traditional cocoa processing, the end of fermentation is
      empirically determined by the workers; consequently, a high variability on the
      quality of fermented cocoa beans is observed. Some physicochemical properties
      (such as fermentation index) have been used to measure the degree of fermentation
      and changes in quality, but only after the fermentation process has concluded,
      using dried cocoa beans. This would suggest that it is necessary to establish a
      relationship between the chemical changes inside the cocoa bean and the
      fermentation conditions during the fermentation in order to standardize the
      process. RESULTS: Cocoa beans were traditionally fermented inside wooden boxes,
      sampled every 24 h and analyzed to evaluate fermentation changes in complete
      bean, cotyledon and dried beans. The value of the fermentation index suggested as
      the minimal adequate (>=1) was observed at 72 h in all bean parts analyzed. At
      this time, values of pH, spectral absorption, total protein hydrolysis and
      vicilin-class globulins of fermented beans suggested that they were well
      fermented. CONCLUSION: Since no difference was found between the types of
      samples, the pH value could be used as a first indicator of the end of the
      fermentation and confirmed by evaluation of the fermentation index using undried
      samples, during the process.

PMID- 23553799
TI  - Nano-sized CT contrast agents.
AB  - Computed tomography (CT) is one of the most widely used clinical imaging
      modalities. In order to increase the sensitivity of CT, small iodinated compounds
      are used as injectable contrast agents. However, the iodinated contrast agents
      are excreted through the kidney and have short circulation times. This rapid
      renal clearance not only restricts in vivo applications that require long
      circulation times but also sometimes induces serious adverse effects related to
      the excretion pathway. In addition, the X-ray attenuation of iodine is not
      efficient for clinical CT that uses high-energy X-ray. Due to these limitations,
      nano-sized iodinated CT contrast agents have been developed that can increase the
      circulation time and decrease the adverse effects. In addition to iodine,
      nanoparticles based on heavy atoms such as gold, lanthanides, and tantalum are
      used as more efficient CT contrast agents. In this review, we summarize the
      recent progresses made in nano-sized CT contrast agents.

PMID- 23553800
TI  - MR microscopy of the human finger and correlation with histology--a proof-of
      principle study.
AB  - Magnetic resonance imaging (MRI) with small surface coils is a well established
      method for the diagnostic evaluation of finger masses. Until now, histological
      examination has been required to reliably assess tumor extent and infiltration of
      surrounding structures. Ultra-high-field MR microscopy (MRM) allows evaluation of
      anatomical structures and pathologies with submillimeter resolution. This study
      describes the diagnostic prospects and potential of MRM based on the ex-vivo
      examination of different finger pathologies. Ten human digits were examined by ex
      vivo MRM at 7.1 Tesla (ClinScan, Bruker BioScan) using a T2-weighted turbo spin
      echo (TSE) sequence. Imaging parameters were: TE 48 ms; TR 8370 ms; slice
      thickness 700 um; matrix size 1024 * 1024 pixels; FOV 37 * 37 mm; in-plane
      resolution 36 * 36 um/voxel. Afterwards specimens were examined histologically.
      Histology and MRM were correlated. MRM allowed evaluation of the anatomy of the
      nail, the tendon insertions, the distal interphalangeal joint, and the
      neurovascular bundles. Finger abnormalities evaluated by MRM included
      osteomyelitis and metastatic disease. Subsequent histological examination
      confirmed MRM findings regarding origin, internal makeup, and extent of the
      structures visualized. This study demonstrates the potential of MRM for imaging
      small anatomical structures and pathologies of the human finger. Our ex-vivo
      findings correlate strongly with histology, suggesting that MRM may gain a
      central role in assessing anatomical structures and pathology in terms of
      morphology, extent, and infiltration of surrounding structures. Therefore, with
      increasing availability, MRM is expected to become an essential tool not only in
      experimental studies but also for daily routine.

PMID- 23553802
TI  - Biomechanics of a short stem: In vitro primary stability and stress shielding of
      a conservative cementless hip stem.
AB  - Short stem prostheses provide conservative surgery and favorable metaphyseal load
      transmission. However, clinical long-term results are lacking. Therefore, in
      vitro trials can be used to predict bone-implant performance. In this in vitro
      study, primary stability and stress shielding of a new cementless short stem
      implant was evaluated in comparison to a straight stem using nine pairs of human
      cadaver femurs. Primary stability, including reversible micromotion and
      irreversible migration, was assessed in a hip simulator. Furthermore, changes in
      the pattern of cortical strain were evaluated. The short stem was more resistant
      to reversible micromotion and irreversible migration into retroversion. Axial
      stability was similar, with mean reversible micromotions of 9 um for the short
      stem and 7 um for the straight stem. Proximal load transmission was more
      physiological with the short stem, though both implants could not avoid stress
      shielding in Gruen zones 1 and 7. Primary stability of the short stem prosthesis
      was not negatively influenced compared to the straight shaft. Furthermore,
      proximal femoral strain pattern was more physiological after insertion of the
      short stem prosthesis.

PMID- 23553801
TI  - Transduction-specific ATLAS reveals a cohort of highly active L1 retrotransposons
      in human populations.
AB  - Long INterspersed Element-1 (LINE-1 or L1) retrotransposons are the only
      autonomously active transposable elements in the human genome. The average human
      genome contains ~80-100 active L1s, but only a subset of these L1s are highly
      active or 'hot'. Human L1s are closely related in sequence, making it difficult
      to decipher progenitor/offspring relationships using traditional phylogenetic
      methods. However, L1 mRNAs can sometimes bypass their own polyadenylation signal
      and instead utilize fortuitous polyadenylation signals in 3' flanking genomic
      DNA. Retrotransposition of the resultant mRNAs then results in lineage specific
      sequence "tags" (i.e., 3' transductions) that mark the descendants of active L1
      progenitors. Here, we developed a method (Transduction-Specific Amplification
      Typing of L1 Active Subfamilies or TS-ATLAS) that exploits L1 3' transductions to
      identify active L1 lineages in a genome-wide context. TS-ATLAS enabled the
      characterization of a putative active progenitor of one L1 lineage that includes
      the disease causing L1 insertion L1RP , and the identification of new
      retrotransposition events within two other "hot" L1 lineages. Intriguingly, the
      analysis of the newly discovered transduction lineage members suggests that L1
      polyadenylation, even within a lineage, is highly stochastic. Thus, TS-ATLAS
      provides a new tool to explore the dynamics of L1 lineage evolution and
      retrotransposon biology.

PMID- 23553803
TI  - Efficacy of Ganoderma sp. JAS4 in bioremediation of chlorpyrifos and its
      hydrolyzing metabolite TCP from agricultural soil.
AB  - A novel fungal strain JAS4 was isolated from agricultural soil and was found to
      be highly effective in degrading chlorpyrifos and its major degradation product
      3,5,6-trichloro-2-pyridinol (TCP). The molecular characterization based on 18S
      rRNA sequence analysis, revealed strain JAS4 as Ganoderma sp. which could able to
      degrade chlorpyrifos and its metabolite in an aqueous medium with rate constant
      of 0.8460 day(-1), following first order rate kinetics, and the time in which the
      initial insecticide concentration was reduced by 50% (DT(50)) was 0.81 days.
      Studies on biodegradation in soil with nutrients showed that JAS4 strain
      exhibited efficient degradation of insecticide with a rate constant of 0.9 day(
      1), and DT(50) was 0.73 day. In contrast, degradation of insecticide in soil
      without nutrients was characterized by a rate constant of 0.7576 day(-1) and the
      DT(50) was 0.91 day.

PMID- 23553805
TI  - Noninvasive automated motion assessment of intestinal motility by continuously
      tagged MR imaging.
AB  - PURPOSE: To evaluate continuously tagged 3 Tesla MRI for monitoring glucagon
      induced bowel motility changes in healthy volunteers. MATERIALS AND METHODS:
      After standardized oral bowel preparation, 10 healthy volunteers underwent a free
      breathing, continuously tagged three-dimensional (3D) dynamic fast-field-echo
      (FFE), at a 3.36 Hz sampling frequency. One milligram of glucagon was
      administered intravenously during data acquisition. Each dataset was divided into
      four temporal sets of 2 min (period 1 to 4). Taglines were tracked automatically
      using a scale spaced based algorithm. Assessment of global spectral resolution
      was performed for three frequency intervals: 0.008-0.300 Hz (motility), 0.300
      0.400 Hz (breathing motion), and 0.400-0.533 Hz (higher order motion). Additional
      analyses were performed at fine spectral resolution in frequency bands of 0.033
      Hz. Glucagon-induced motility changes were investigated by means of a motility
      index (spectral power normalized to the maximal spectral power per-volunteer),
      resulting in a range of 0 to 1 (no motion to maximal motion). Statistical
      comparison was done for period 1 and 4 (Wilcoxon-signed rank test). RESULTS:
      After glucagon administration, a significant decrease in the motility index was
      found for the low- (0.008-0.300 Hz) (P < 0.0001) and high-frequency interval
      (0.400-0.533 Hz) (P < 0.0001). Around breathing motion frequencies, no decrease
      in motility index was detected. CONCLUSION: Free-breathing, continuously tagged
      MR imaging is a noninvasive method for automated bowel motility assessment and
      allows for detection of drug-induced changes.

PMID- 23553804
TI  - Gremlin aggravates hyperglycemia-induced podocyte injury by a TGFbeta/smad
      dependent signaling pathway.
AB  - Gremlin is a bone morphogenic protein (BMP) antagonist and is elevated in
      diabetic kidney tissues. In the early course of diabetic nephropathy (DN),
      podocyte are injured. We studied the protein and gene expression of gremlin in
      mice podocytes cultured in hyperglycemia ambient. The role of gremlin on podocyte
      injury and the likely signaling pathways involved were determined. Expression of
      gremlin was visualized by confocal microscopy. Recombinant mouse gremlin and
      small interfering RNA (siRNA) targeting to gremlin1 identified the role played by
      gremlin on podocytes. Study of canonical (smad2/3) and non-canonical (p38MAPK and
      JNK1/2) transforming growth factor beta (TGFbeta)/smad mediated signaling
      revealed the putative signaling mechanisms involved. Smad2/3 siRNA and TGFbeta
      receptor inhibition (SB431542) were used to probe canonical TGFbeta/smad
      signaling in gremlin-induced podocyte injury. Apoptosis of podocytes was measured
      by TUNEL assay. Gremlin expression was enhanced in high glucose cultured mouse
      podocytes, and was localized predominantly in the cytoplasm and negligibly on the
      cell membrane. Not only expression of nephrin and synaptopodin were decreased on
      treatment with gremlin, but also synaptopodin rearrangement and nephrin
      relocalization were evident. Knockdown gremlin1 or smad2/3 by siRNA, and
      inhibition of TGFbetaR (SB431542) attenuated podocyte injury. Inhibition of
      canonical TGF-beta signal blocked the injury of gremlin on podocytes. In
      conclusion, gremlin was clearly elevated in high glucose cultured mouse
      podocytes, and likely employed endogenous canonical TGFbeta1/Smad signaling to
      induce podocyte injury. Knockdown gremlin1 by siRNA may be clinically useful in
      the attenuation of podocyte injury.

PMID- 23553806
TI  - Spinal astrocytes stimulated by tumor necrosis factor-alpha and/or interferon
      gamma attenuate connexin 43-gap junction via c-jun terminal kinase activity.
AB  - Spinal astrocytes have important mechanistic contributions to the initiation and
      maintenance of neurodegenerative diseases and chronic pain. Under inflammatory
      conditions, spinal astrocytes are exposed to cytokines such as tumor necrosis
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), and these cytokines
      could alter astrocytic function by modulating connexin (Cx43), subunits that form
      channels that modulate intercellular communication in astrocytes. The current
      study investigated the alteration of Cx43-gap junction in rat primary cultured
      spinal astrocytes stimulated with cytokines by real-time PCR and Western
      blotting. The transcriptional and translational levels of Cx43 were significantly
      but partially reduced 24 and 48 hr treatment with either TNF-alpha (10 ng/ml) or
      IFN-gamma (5 ng/ml). A mixture of TNF-alpha and IFN-gamma led to a robust
      decrease of Cx43 expression and, moreover, a moderate reduction of gap junction
      intercellular communication (GJIC), which was evaluated by a scrap loading/dye
      transfer assay. Both the decrease of Cx43 expression and the reduction in GJIC
      induced by the mixture of TNF-alpha and IFN-gamma were prevented by blocking c
      jun terminal kinase (JNK) but not by blocking extracellular signaling molecules
      ERK and p38 kinase, indicating a specific role of astrocytic JNK in the response
      to cytokines. In addition, treatment with cytokines potently induced the
      phosphorylation of JNK and c-jun in a time-dependent manner. These results
      indicate that intercellular communication of astrocytes is significantly
      disrupted in the inflammatory state and that stimulation of spinal astrocytes
      with inflammatory cytokines leads to significant inhibition of Cx43-GJIC through
      activation of the JNK signaling pathway.

PMID- 23553807
TI  - Interleukin-21 in chronic inflammatory diseases.
AB  - Interleukin-21 (IL-21), a cytokine produced by various subsets of activated CD4+
      T cells, regulates multiple innate and adaptive immune responses. Indeed, IL-21
      controls the proliferation and function of CD4+ and CD8+ T lymphocytes, drives
      the differentiation of B cells into memory cells and Ig-secreting plasma cells,
      enhances the activity of natural killer cells and negatively regulates the
      differentiation and activity of regulatory T cells. Moroever, IL-21 can stimulate
      nonimmune cells to synthesize various inflammatory molecules. Excessive
      production of IL-21 has been described in many human chronic inflammatory
      disorders and there is evidence that blockade of IL-21 helps attenuate
      detrimental responses in mouse models of immune-mediated diseases. In this
      article we briefly review data supporting the pathogenic role of IL-21 in immune
      inflammatory pathologies and discuss the benefits and risks of IL-21
      neutralization in patients with such diseases.

PMID- 23553808
TI  - Evaluation of pharmacologic prophylaxis for venous thromboembolism in patients
      with chronic liver disease.
AB  - STUDY OBJECTIVE: To determine whether pharmacologic prophylaxis for venous
      thromboembolism (VTE) was associated with a decrease in the incidence of VTE or
      an increased incidence of bleeding in patients with chronic liver disease (CLD).
      DESIGN: Single-center, retrospective cohort analysis. SETTING: University medical
      center. PATIENTS: A total of 1581 adults with CLD hospitalized over a 3-year
      period for longer than 24 hours. MEASUREMENTS AND MAIN RESULTS: Medical records
      were reviewed for the primary outcome of VTE and documented episodes of bleeding
      during hospitalization and were divided into two groups based on receipt of
      pharmacologic VTE prophylaxis. During the 1581 hospitalizations, 392 (24.7%)
      patients received pharmacologic VTE prophylaxis. The incidence of VTE in the
      prophylaxis group was 0.5% compared with 1.8% in patients without prophylaxis
      (p=0.05). Documented bleeding rates were lower in the prophylaxis group (2.0% vs
      10.3%, p<0.001). Multivariate logistic regression identified active malignancy
      (odds ratio [OR] 8.76, 95% confidence interval [CI], 2.56-29.58), trauma or
      surgery during hospitalization (OR 10.29, 95% CI 1.18-89.51), and history of VTE
      (OR 26.48, 95% CI 6.93-101.16) as risk factors of VTE. Use of pharmacologic VTE
      prophylaxis was protective against VTE (OR 0.34, 95% CI 0.04-0.88). CONCLUSION:
      Pharmacologic VTE prophylaxis was associated with a decreased incidence of VTE in
      patients with CLD without an increased rate of bleeding and should be routinely
      considered on admission to the hospital. Patients with CLD and active malignancy,
      trauma or surgery during hospitalization, or history of VTE appear to be at
      highest risk of VTE and thus warrant pharmacologic prophylaxis. Prospective
      studies must validate these findings.

PMID- 23553809
TI  - Cost and quality implications of opioid-based postsurgical pain control using
      administrative claims data from a large health system: opioid-related adverse
      events and their impact on clinical and economic outcomes.
AB  - STUDY OBJECTIVE: To determine the prevalence of postsurgical opioid use in the
      inpatient setting, to ascertain the frequency of and risk factors for opioid
      related adverse drug events (ORADEs) among patients who received opioids, and to
      evaluate the impact of ORADEs on clinical and economic outcomes. DESIGN:
      Retrospective cohort study using administrative data. SETTING: Hospital system
      encompassing 26 hospitals in the southeastern United States. PATIENTS: A total of
      37,031 patients aged 18 years or older who underwent a common surgical procedure
      between January 1, 2009, and December 31, 2010. MEASUREMENTS AND MAIN RESULTS:
      Patients were evaluated for receipt of postsurgical opioids. Outcomes among
      opioid users included ORADE rates, hospital length of stay, total hospitalization
      costs, 30-day readmission rates, outlier status, and inpatient mortality. Factors
      associated with ORADEs were evaluated; length of stay, costs, readmissions, and
      mortality were compared between patients experiencing and not experiencing ORADEs
      by using propensity score matching on age, race-ethnicity, sex, presurgery opioid
      use, and comorbidities. Length of stay and cost rate ratios were generated by
      using negative binomial regression and generalized linear models. Odds ratios for
      30-day readmissions and inpatient mortality were generated by using logistic
      regression. Among all surgical patients, 36,529 (98.6%) of patients received
      opioids, of whom 4955 (13.6%) experienced an ORADE. Increased risk of ORADEs was
      associated with age 65 years or older, male sex, obesity, presurgery opioid use,
      and higher score on Charlson Comorbidity Index. Patients with an ORADE had a 55%
      longer length of stay, 47% higher costs of care, 36% increased risk of 30-day
      readmission, and 3.4 times higher risk of inpatient mortality than did patients
      who did not experience an ORADE. CONCLUSION: Opioid use was ubiquitous among
      hospitalized patients who underwent common surgical procedures. The observed
      negative outcomes of ORADEs and their impact on patients and the health care
      system should be considered when evaluating the balance between effectively
      managing postsurgical pain while minimizing the risk of ORADEs.

PMID- 23553810
TI  - Hypoactive sexual desire disorder in women: treatment options beyond testosterone
      and approaches to communicating with patients on sexual health.
AB  - Hypoactive sexual desire disorder (HSDD) affects nearly 1 in 10 women. Thus, it
      is essential for pharmacists and other health care providers to be comfortable
      when discussing a patient's sexual health to ensure appropriate triage so that
      the specific causes of HSDD can be identified and potential recommendations
      provided. HSDD is defined as the absence or deficiency of sexual interest and/or
      desire, leading to significant distress and interpersonal difficulties. As health
      care providers, pharmacists have a critical role in assessing the presence of
      HSDD and providing education on available treatment options. This article will
      review the potential causes of HSDD and low sexual desire, the screening tools
      available, and the significant role of health care professionals in communicating
      with patients about their sexual health. An overview of the importance of
      behavioral modifications, the current pharmacologic options being investigated,
      and the use of complementary and alternative therapies will also be explored.
      Currently, buproprion is the primary pharmacologic agent that has shown positive
      results in treating patients with HSDD. The use of testosterone therapy will not
      be addressed in this article, as this therapy is described in greater detail
      elsewhere.

PMID- 23553811
TI  - Clinical update on the management of atrial fibrillation.
AB  - Atrial fibrillation (AF) is a cardiac arrhythmia associated with significant
      morbidity and mortality, affecting more than 3 million people in the United
      States and 1-2% of the population worldwide. Its estimated prevalence is expected
      to double within the next 50 years. During the past decade, there have been
      significant advances in the treatment of AF. Studies have demonstrated that a
      rate control strategy, with a target resting heart rate between 80 and 100
      beats/minute, is recommended over rhythm control in the vast majority of
      patients. The CHA2 DS2 >= (congestive heart failure, hypertension, age >= 65 yrs,
      diabetes mellitus, stroke or transient ischemic attack, vascular disease, female
      gender) scoring system is a potentially useful stroke risk stratification tool
      that incorporates additional risk factors to the commonly used CHADS2 (congestive
      heart failure, hypertension, age >= 75 years, diabetes mellitus, stroke transient
      ischemic attack) scoring tool. Similarly, a convenient scheme, termed HAS-BLED
      (hypertension, abnormal renal/liver function, stroke, bleeding history or
      predisposition, labile international normalized ratio, elderly, drugs/alcohol
      concomitantly), to assess bleeding risk has emerged that may be useful in select
      patients. Furthermore, new antithrombotic strategies have been developed as
      potential alternatives to warfarin, including dual-antiplatelet therapy with
      clopidogrel plus aspirin and the development of new oral anticoagulants such as
      dabigatran, rivaroxaban, and apixaban. Vernakalant has emerged as another
      potential option for pharmacologic conversion of AF, whereas recent trials have
      better defined the role of dronedarone in the maintenance of sinus rhythm.
      Finally, catheter ablation represents another alternative to manage AF, whereas
      upstream therapy with inhibitors of the renin-angiotensin-aldosterone system,
      statins, and polyunsaturated fatty acids could potentially prevent the occurrence
      of AF. Despite substantial progress in the management of AF, significant
      uncertainty surrounds the optimal treatment of this condition.

PMID- 23553812
TI  - Evaluation of proprotein convertase subtilisin/kexin type 9: focus on potential
      clinical and therapeutic implications for low-density lipoprotein cholesterol
      lowering.
AB  - Reduction in low-density lipoprotein cholesterol (LDL-C) is associated with a
      decrease in coronary heart disease (CHD). Statins are currently the most
      effective medications for LDL-C lowering; however, there continues to be a
      residual risk for cardiovascular events. Proprotein convertase subtilisin/kexin
      type 9 (PCSK9) is a protease that promotes LDL receptor degradation, leading to
      an increase in LDL-C blood levels. Patients with PCSK9 gain-of-function mutations
      can have up to a 20-fold increase in associated CHD compared with patients
      without these mutations. Conversely, patients with PCSK9 loss-of-function
      mutations can have up to an 88% reduction in CHD without any deficits in
      neurologic or physiologic functions. PCSK9 can be modulated by current
      antihyperlipidemic therapies. In particular, statins lead to an increase in
      PCSK9, which may attenuate their full lipid-lowering effects. These attributes
      have made PCSK9 inhibition a desirable target for future drug therapies. Current
      investigational modalities inhibiting PCSK9 will also be discussed.

PMID- 23553813
TI  - Propensity scores used for analysis of cluster randomized trials with selection
      bias: a simulation study.
AB  - Cluster randomized trials (CRTs) are often prone to selection bias despite
      randomization. Using a simulation study, we investigated the use of propensity
      score (PS) based methods in estimating treatment effects in CRTs with selection
      bias when the outcome is quantitative. Of four PS-based methods (adjustment on
      PS, inverse weighting, stratification, and optimal full matching method), three
      successfully corrected the bias, as did an approach using classical multivariable
      regression. However, they showed poorer statistical efficiency than classical
      methods, with higher standard error for the treatment effect, and type I error
      much smaller than the 5% nominal level.

PMID- 23553814
TI  - HOXA13 regulates Aldh1a2 expression in the autopod to facilitate interdigital
      programmed cell death.
AB  - BACKGROUND: Retinoic acid (RA), plays an essential role in the growth and
      patterning of vertebrate limb. While the developmental processes regulated by RA
      are well understood, little is known about the transcriptional mechanisms
      required to precisely control limb RA synthesis. Here, Aldh1a2 functions as the
      primary enzyme necessary for RA production which regulates forelimb outgrowth and
      hindlimb digit separation. Because mice lacking HOXA13 exhibit similar defects in
      digit separation as Aldh1a2 mutants, we hypothesized that HOXA13 regulates
      Aldh1a2 to facilitate RA-mediated interdigital programmed cell death (IPCD) and
      digit separation. RESULTS: In this report, we identify Aldh1a2 as a direct target
      of HOXA13. In absence of HOXA13 function, Aldh1a2 expression, RA signaling, and
      IPCD are reduced. In the limb, HOXA13 binds a conserved cis-regulatory element in
      the Aldh1a2 locus that can be regulated by HOXA13 to promote gene expression.
      Finally, decreased RA signaling and IPCD can be partially rescued in the Hoxa13
      mutant hindlimb by maternal RA supplementation. CONCLUSIONS: Defects in IPCD and
      digit separation in Hoxa13 mutant mice may be caused in part by reduced levels of
      RA signaling stemming from a loss in the direct regulation of Aldh1a2. These
      findings provide new insights into the transcriptional regulation of RA signaling
      necessary for limb morphogenesis.

PMID- 23553815
TI  - Direct water splitting into hydrogen and oxygen under visible light by using
      modified TaON photocatalysts with d(0) electronic configuration.

PMID- 23553816
TI  - Disease-causing mitochondrial heteroplasmy segregated within induced pluripotent
      stem cell clones derived from a patient with MELAS.
AB  - Mitochondrial diseases display pathological phenotypes according to the mixture
      of mutant versus wild-type mitochondrial DNA (mtDNA), known as heteroplasmy. We
      herein examined the impact of nuclear reprogramming and clonal isolation of
      induced pluripotent stem cells (iPSC) on mitochondrial heteroplasmy. Patient
      derived dermal fibroblasts with a prototypical mitochondrial deficiency diagnosed
      as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
      (MELAS) demonstrated mitochondrial dysfunction with reduced oxidative reserve due
      to heteroplasmy at position G13513A in the ND5 subunit of complex I.
      Bioengineered iPSC clones acquired pluripotency with multilineage differentiation
      capacity and demonstrated reduction in mitochondrial density and oxygen
      consumption distinguishing them from the somatic source. Consistent with the
      cellular mosaicism of the original patient-derived fibroblasts, the MELAS-iPSC
      clones contained a similar range of mtDNA heteroplasmy of the disease-causing
      mutation with identical profiles in the remaining mtDNA. High-heteroplasmy iPSC
      clones were used to demonstrate that extended stem cell passaging was sufficient
      to purge mutant mtDNA, resulting in isogenic iPSC subclones with various degrees
      of disease-causing genotypes. On comparative differentiation of iPSC clones,
      improved cardiogenic yield was associated with iPSC clones containing lower
      heteroplasmy compared with isogenic clones with high heteroplasmy. Thus, mtDNA
      heteroplasmic segregation within patient-derived stem cell lines enables direct
      comparison of genotype/phenotype relationships in progenitor cells and lineage
      restricted progeny, and indicates that cell fate decisions are regulated as a
      function of mtDNA mutation load. The novel nuclear reprogramming-based model
      system introduces a disease-in-a-dish tool to examine the impact of mutant
      genotypes for MELAS patients in bioengineered tissues and a cellular probe for
      molecular features of individual mitochondrial diseases.

PMID- 23553818
TI  - Asymmetric auto-tandem catalysis with a planar-chiral ruthenium complex:
      sequential allylic amidation and atom-transfer radical cyclization.

PMID- 23553819
TI  - Domain-averaged exchange-correlation energies as a physical underpinning for
      chemical graphs.
AB  - A novel solution to the problem of assigning a molecular graph to a collection of
      nuclei (i.e. how to draw a molecular structure) is presented. Molecules are
      universally understood as a set of nuclei linked by bonds, but establishing which
      nuclei are bonded and which are not is still an empirical matter. Our approach
      borrows techniques from quantum chemical topology, which showed for the first
      time the construction of chemical graphs from wave functions, shifting the focus
      on energetics. This new focus resolves issues surrounding previous topological
      analyses, in which domain-averaged exchange-correlation energies (V(xc)),
      quantities defined in real space between each possible atom pair, hold the key.
      Exponential decay of V(xc) in non-metallic systems as the intercenter distance
      increases guarantees a well-defined hierarchy for all possible V(xc) values in a
      molecule. Herein, we show that extracting the set of atom pairs that display the
      largest V(xc) values in the hierarchy is equivalent to retrieving the molecular
      graph itself. Notably, domain-averaged exchange-correlation energies are
      transferable, and they can be used to calculate bond strengths. Fine-grained
      details resulted to be related to simple stereoelectronic effects. These ideas
      are demonstrated in a set of simple pilot molecules.

PMID- 23553820
TI  - Crystal structures of Klebsiella pneumoniae pantothenate kinase in complex with N
      substituted pantothenamides.
AB  - N-Substituted pantothenamides are derivatives of pantothenate, the precursor in
      the biosynthesis of the essential metabolic cofactor coenzyme A (CoA). These
      compounds are substrates of pantothenate kinase (PanK) in the first step of CoA
      biosynthesis and possess antimicrobial activity against various pathogenic
      bacteria. Here we solved the crystal structure of the Klebsiella pneumoniae PanK
      (KpPanK) in complex with N-pentylpantothenamide (N5-Pan) to understand the
      molecular basis of its antimicrobial activity. The structure reveals a polar
      pocket interacting with the pantothenate moiety of N5-Pan and an aromatic pocket
      loosely protecting the pentyl tail, suggesting that the introduction of an
      aromatic ring to a new pantothenamide may enhance the compound's affinity to
      KpPanK. To test this idea, we synthesized N-pyridin-3-ylmethylpantothenamide (Np
      Pan) and solved its co-crystal structure with KpPanK. The structure reveals two
      alternat conformations of the aromatic ring of Np-Pan bound at the aromatic
      pocket, providing the basis for further improvement of pantothenamide binding to
      KpPanK.

PMID- 23553821
TI  - Could some coral reefs become sponge reefs as our climate changes?
AB  - Coral reefs across the world have been seriously degraded and have a bleak future
      in response to predicted global warming and ocean acidification (OA). However,
      this is not the first time that biocalcifying organisms, including corals, have
      faced the threat of extinction. The end-Triassic mass extinction (200 million
      years ago) was the most severe biotic crisis experienced by modern marine
      invertebrates, which selected against biocalcifiers; this was followed by the
      proliferation of another invertebrate group, sponges. The duration of this sponge
      dominated period far surpasses that of alternative stable-ecosystem or phase
      shift states reported on modern day coral reefs and, as such, a shift to sponge
      dominated reefs warrants serious consideration as one future trajectory of coral
      reefs. We hypothesise that some coral reefs of today may become sponge reefs in
      the future, as sponges and corals respond differently to changing ocean chemistry
      and environmental conditions. To support this hypothesis, we discuss: (i) the
      presence of sponge reefs in the geological record; (ii) reported shifts from
      coral- to sponge-dominated systems; and (iii) direct and indirect responses of
      the sponge holobiont and its constituent parts (host and symbionts) to changes in
      temperature and pH. Based on this evidence, we propose that sponges may be one
      group to benefit from projected climate change and ocean acidification scenarios,
      and that increased sponge abundance represents a possible future trajectory for
      some coral reefs, which would have important implications for overall reef
      functioning. 

PMID- 23553817
TI  - A decade and a half of protein intrinsic disorder: biology still waits for
      physics.
AB  - The abundant existence of proteins and regions that possess specific functions
      without being uniquely folded into unique 3D structures has become accepted by a
      significant number of protein scientists. Sequences of these intrinsically
      disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number
      of specific features, such as low overall hydrophobicity and high net charge
      which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic
      volumes, low contents of ordered secondary structure, and are characterized by
      high structural heterogeneity. They are very flexible, but some may undergo
      disorder to order transitions in the presence of natural ligands. The degree of
      these structural rearrangements varies over a very wide range. IDPs/IDPRs are
      tightly controlled under the normal conditions and have numerous specific
      functions that complement functions of ordered proteins and domains. When lacking
      proper control, they have multiple roles in pathogenesis of various human
      diseases. Gaining structural and functional information about these proteins is a
      challenge, since they do not typically "freeze" while their "pictures are taken."
      However, despite or perhaps because of the experimental challenges, these fuzzy
      objects with fuzzy structures and fuzzy functions are among the most interesting
      targets for modern protein research. This review briefly summarizes some of the
      recent advances in this exciting field and considers some of the basic lessons
      learned from the analysis of physics, chemistry, and biology of IDPs.

PMID- 23553822
TI  - Altered thermogenesis and impaired bone remodeling in Misty mice.
AB  - Fat mass may be modulated by the number of brown-like adipocytes in white adipose
      tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic
      energy metabolism and, with age, bone remodeling becomes uncoupled and brown
      adipose tissue (BAT) function declines. To test the interaction between BAT and
      bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We
      found that Misty mice have accelerated age-related trabecular bone loss and
      impaired brown fat function (including reduced temperature, lower expression of
      Pgc1a, and less sympathetic innervation compared to wild-type (+/ +)). Despite
      reduced BAT function, Misty mice had normal core body temperature, suggesting
      heat is produced from other sources. Indeed, upon acute cold exposure (4 degrees
      C for 6 hours), inguinal WAT from Misty mice compensated for BAT dysfunction by
      increasing expression of Acadl, Pgc1a, Dio2, and other thermogenic genes.
      Interestingly, acute cold exposure also decreased Runx2 and increased Rankl
      expression in Misty bone, but only Runx2 was decreased in wild-type. Browning of
      WAT is under the control of the sympathetic nervous system (SNS) and, if present
      at room temperature, could impact bone metabolism. To test whether SNS activity
      could be responsible for accelerated trabecular bone loss, we treated wild-type
      and Misty mice with the beta-blocker, propranolol. As predicted, propranolol
      slowed trabecular bone volume/total volume (BV/TV) loss in the distal femur of
      Misty mice without affecting wild-type. Finally, the Misty mutation (a truncation
      of DOCK7) also has a significant cell-autonomous role. We found DOCK7 expression
      in whole bone and osteoblasts. Primary osteoblast differentiation from Misty
      calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling.
      Despite the multifaceted effects of the Misty mutation, we have shown that
      impaired brown fat function leads to altered SNS activity and bone loss, and for
      the first time that cold exposure negatively affects bone remodeling. 

PMID- 23553823
TI  - Local anesthetic effects on gene transcription in human skeletal muscle biopsies.
AB  - INTRODUCTION: We examined if epinephrine in the local anesthetic to help control
      incision-related bleeding interferes with molecular measurements obtained with
      the Duchenne-Bergstrom percutaneous needle biopsy technique for sampling human
      skeletal muscle. METHODS: Three groups received 2.5-3.0 ml of 1% lidocaine in 2
      injections: (1) 0.5-1.0 ml superficially, which varied among the groups according
      to (i) -Epi; intra- and subcutaneous without epinephrine, (ii) +Epi -Fascia;
      intra- and subcutaneous with epinephrine, avoiding the fascia, and (iii) +Epi
      +Fascia; intra- and subcutaneous with epinephrine, directing a small amount (?0.2
      ml) into the fascia area; and (2) ?2.0 ml without epinephrine into the fascia
      area for all subjects. A muscle biopsy was obtained 5-10 min later for IL-6 and
      MuRF-1 mRNA levels. RESULTS: IL-6 mRNA levels were low in -Epi and +Epi -Fascia,
      but ?300-fold higher in +Epi +Fascia. MuRF-1 mRNA levels were similar among the
      groups. CONCLUSIONS: Lidocaine with epinephrine can confound intramuscular
      measurements from needle biopsies, but this can be avoided with a careful
      injection approach.

PMID- 23553824
TI  - Chemical composition and bioactivity of different oregano (Origanum vulgare)
      extracts and essential oil.
AB  - BACKGROUND: There is a growing interest in industry to replace synthetic
      chemicals by natural products with bioactive properties. Aromatic plants are
      excellent sources of bioactive compounds that can be extracted using several
      processes. As far as oregano is concerned, studies are lacking addressing the
      effect of extraction processes in bioactivity of extracts. This study aimed to
      characterise the in vitro antioxidant and antibacterial properties of oregano
      (Origanum vulgare) essential oil and extracts (in hot and cold water, and
      ethanol), and the chemical composition of its essential oil. RESULTS: The major
      components of oregano essential oil were carvacrol, beta-fenchyl alcohol, thymol,
      and gamma-terpinene. Hot water extract had the strongest antioxidant properties
      and the highest phenolic content. All extracts were ineffective in inhibiting the
      growth of the seven tested bacteria. In contrast, the essential oil inhibited the
      growth of all bacteria, causing greater reductions on both Listeria strains (L.
      monocytogenes and L. innocua). CONCLUSION: O. vulgare extracts and essential oil
      from Portuguese origin are strong candidates to replace synthetic chemicals used
      by the industry.

PMID- 23553825
TI  - MRT letter: visual attention driven framework for hysteroscopy video abstraction.
AB  - Diagnostic hysteroscopy is a popular method for investigating the regions in the
      female reproductive system. The videos generated by hysteroscopy sessions of
      patients are recurrently archived in medical libraries. Gynecologists often need
      to browse these libraries in search of similar cases or for reviewing old videos
      of a patient. Diagnostic hysteroscopy videos contain a lot of information with
      abundant redundancy. Key frame extraction-based video summarization can be used
      to reduce this huge amount of data. Moreover, key frames can be used for browsing
      and indexing of hysteroscopy videos. In this article, a domain specific visual
      attention driven framework for summarization of hysteroscopy videos is proposed.
      The visual attention model is materialized by computing saliency based on color,
      texture, and motion. The experimental results, in comparison with other
      techniques, demonstrate the efficacy of the proposed framework.

PMID- 23553826
TI  - The thyroid foramen: a systematic review and surgical considerations.
AB  - This study presents an analytic review about the trait of the thyroid foramen. A
      detailed description about the demographics, frequency, embryology, morphometry,
      possible content, topography, clinical and surgical considerations is provided.
      The overall frequency was 28.3% in adults, 15% in children and neonates, 40.6% in
      embryos and fetuses. The content of the thyroid foramina was a neurovascular
      bundle in 41.2% of studies. An equal number of studies define a nerve as the
      common content, while only in 17.6% the usual content was a vessel.
      Interestingly, in 11.8% the content was just connective tissue or a pit. An
      updated classification is presented taking into account all the possible content
      that can cross through a thyroid foramen. The variant is of high interest for
      surgeons intervening in the larynx due to potential complications such as local
      bleeding and unwanted neural impairment. The oblique line of the thyroid lamina
      acts as the best topographical landmark to identify any aberrant anatomy related
      to a thyroid foramen.

PMID- 23553827
TI  - Effect of elastin digestion on the quasi-static tensile response of medial
      collateral ligament.
AB  - Elastin is a structural protein that provides resilience to biological tissues.
      We examined the contributions of elastin to the quasi-static tensile response of
      porcine medial collateral ligament through targeted disruption of the elastin
      network with pancreatic elastase. Elastase concentration and treatment time were
      varied to determine a dose response. Whereas elastin content decreased with
      increasing elastase concentration and treatment time, the change in peak stress
      after cyclic loading reached a plateau above 1 U/ml elastase and 6 h treatment.
      For specimens treated with 2 U/ml elastase for 6 h, elastin content decreased
      approximately 35%. Mean peak tissue strain after cyclic loading (4.8%, p >=
      0.300), modulus (275 MPa, p >= 0.114) and hysteresis (20%, p >= 0.553) were
      unaffected by elastase digestion, but stress decreased significantly after
      treatment (up to 2 MPa, p <= 0.049). Elastin degradation had no effect on failure
      properties, but tissue lengthened under the same pre-stress. Stiffness in the
      linear region was unaffected by elastase digestion, suggesting that enzyme
      treatment did not disrupt collagen. These results demonstrate that elastin
      primarily functions in the toe region of the stress-strain curve, yet contributes
      load support in the linear region. The increase in length after elastase
      digestion suggests that elastin may pre-stress and stabilize collagen crimp in
      ligaments.

PMID- 23553828
TI  - Hierarchical tubular structures constructed by carbon-coated SnO(2) nanoplates
      for highly reversible lithium storage.
AB  - Hierarchical tubular structures constructed by ultrathin carbon-coated SnO(2)
      nanoplates are rationally designed and synthesized. This interesting structure
      simultaneously integrates the structural and compositional design rationales for
      high-energy anode materials based on low-dimensional ultrathin nanoplates, a
      hollow tubular structure, and a carbon nanocoating. When evaluated as an anode
      material for lithium-ion batteries, the as-synthesized SnO(2)-carbon hybrid
      structure manifests high specific capacity and excellent cycling stability.

PMID- 23553829
TI  - Wet-plate culture studies of Penicillium sp. PT95 and Q1 for mass production of
      sclerotia.
AB  - Penicillium sp. PT95 and Q1 strains were able to form abundant orange, sand
      shaped sclerotia in which carotenoids were accumulated. To determine the
      potential availability of the wet-plate method for mass production of sclerotia,
      nine kinds of liquid media were used culture the PT95 and Q1 strains. The results
      of the wet-plate culture showed that on 25% glycerol nitrate broth medium, the
      growth of both strains was relatively slow, and no sclerotia were found. Q1
      strain cultured on Czapek's yeast extract broth medium could not form sclerotia.
      On other media, both strains could form sclerotia. For PT95 strain, the highest
      sclerotial biomass (380 mg plate(-1) ) and carotenoids yield (20.88 ug plate(-1)
      ) could be obtained on Czapek's yeast extract broth and Georgiou's liquid medium,
      respectively. For Q1 strain, malt extract broth medium gave the highest
      sclerotial biomass (340 mg plate(-1) ) and omitting iron Joham's liquid medium
      gave the highest carotenoids yield (18.29 ug plate(-1) ). The results from this
      study suggest the potential usage of wet-plate method in the mass production of
      sclerotia of the PT95 and Q1 strains. 

PMID- 23553830
TI  - Diffusion tensor imaging of extraocular muscle using two-dimensional single-shot
      interleaved multiple inner volume imaging diffusion-weighted EPI at 3 tesla.
AB  - PURPOSE: To evaluate the feasibility of diffusion tensor imaging (DTI) for the
      medial and lateral rectus extraocular muscle (EOM) evaluation, to investigate the
      normal DTI parameters of the medial and lateral rectus EOM, and to compare with
      other skeletal muscle. MATERIALS AND METHODS: Seven multiple sclerosis patients
      and five normal subjects (M:F = 5:7, mean age = 31.6 +/- 9.2) without EOM
      disorder were included. The orbital DTIs using 2D-ss-IMVI-DWEPI were scanned with
      b = 500 s/mm(2) and 12 directions. The mean diffusivity (MD) and fractional
      anisotrophy (FA) of medial and lateral rectus EOMs in both orbits, and temporalis
      muscles were measured in regions of interest on two consecutive axial slices.
      Student t-test was performed to compare the mean apparent diffusion coefficient
      and FA values between medial and lateral rectus EOMs, and between EOMs and
      temporalis muscles. RESULTS: The MDs in medial (0.58 +/- 0.18 * 10(-3) mm(2) /s)
      and lateral rectus EOMs (0.71 +/- 0.18 * 10(-3) mm(2) /s) were significantly
      lower than temporalis muscle (0.84 +/- 0.14 * 10(-3) mm(2) /s) (P < 0.001,
      respectively). The MD in medial rectus EOM was significantly lower than lateral
      rectus EOM (P = 0.001). The FAs in medial (0.40 +/- 0.05) and lateral rectus EOMs
      (0.40 +/- 0.05) were significantly higher than temporalis muscle (0.25 +/- 0.05)
      (P < 0.001, respectively). There was no significant difference between the FAs in
      medial and lateral rectus EOMs (P > 0.05). CONCLUSION: The MDs of EOMs were lower
      and the FAs were higher than those of skeletal muscle. These are well correlated
      to the unique characteristics of EOMs.

PMID- 23553831
TI  - NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via
      signaling molecules TrkB and NCAM.
AB  - Small-cell lung cancer and other aggressive neuroendocrine cancers are often
      associated with early dissemination and frequent metastases. We demonstrate that
      neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk
      among survival and migratory-inducing signaling pathways in neuroendocrine lung
      carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in
      aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine
      kinase tropomyosin-related kinase B (TrkB). Like TrkB, the prometastatic
      signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of
      NeuroD1, whose impaired expression mirrors loss of NeuroD1. TrkB and NCAM may be
      therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.

PMID- 23553832
TI  - Epoxide as a precursor to secondary organic aerosol formation from isoprene
      photooxidation in the presence of nitrogen oxides.
AB  - Isoprene is a substantial contributor to the global secondary organic aerosol
      (SOA) burden, with implications for public health and the climate system. The
      mechanism by which isoprene-derived SOA is formed and the influence of
      environmental conditions, however, remain unclear. We present evidence from
      controlled smog chamber experiments and field measurements that in the presence
      of high levels of nitrogen oxides (NO(x) = NO + NO2) typical of urban
      atmospheres, 2-methyloxirane-2-carboxylic acid (methacrylic acid epoxide, MAE) is
      a precursor to known isoprene-derived SOA tracers, and ultimately to SOA. We
      propose that MAE arises from decomposition of the OH adduct of
      methacryloylperoxynitrate (MPAN). This hypothesis is supported by the similarity
      of SOA constituents derived from MAE to those from photooxidation of isoprene,
      methacrolein, and MPAN under high-NOx conditions. Strong support is further
      derived from computational chemistry calculations and Community Multiscale Air
      Quality model simulations, yielding predictions consistent with field
      observations. Field measurements taken in Chapel Hill, North Carolina, considered
      along with the modeling results indicate the atmospheric significance and
      relevance of MAE chemistry across the United States, especially in urban areas
      heavily impacted by isoprene emissions. Identification of MAE implies a major
      role of atmospheric epoxides in forming SOA from isoprene photooxidation.
      Updating current atmospheric modeling frameworks with MAE chemistry could improve
      the way that SOA has been attributed to isoprene based on ambient tracer
      measurements, and lead to SOA parameterizations that better capture the
      dependency of yield on NO(x).

PMID- 23553833
TI  - Proteome-wide profiling of activated transcription factors with a concatenated
      tandem array of transcription factor response elements.
AB  - Transcription factors (TFs) are families of proteins that bind to specific DNA
      sequences, or TF response elements (TFREs), and function as regulators of many
      cellular processes. Because of the low abundance of TFs, direct quantitative
      measurement of TFs on a proteome scale remains a challenge. In this study, we
      report the development of an affinity reagent that permits identification of
      endogenous TFs at the proteome scale. The affinity reagent is composed of a
      synthetic DNA containing a concatenated tandem array of the consensus TFREs
      (catTFRE) for the majority of TF families. By using catTFRE to enrich TFs from
      cells, we were able to identify as many as 400 TFs from a single cell line and a
      total of 878 TFs from 11 cell types, covering more than 50% of the gene products
      that code for the DNA-binding TFs in the genome. We further demonstrated that
      catTFRE pull-downs could quantitatively measure proteome-wide changes in DNA
      binding activity of TFs in response to exogenous stimulation by using a label
      free MS-based quantification approach. Applying catTFRE on the evaluation of drug
      effects, we described a panoramic view of TF activations and provided candidates
      for the elucidation of molecular mechanisms of drug actions. We anticipate that
      the catTFRE affinity strategy will find widespread applications in biomedical
      research.

PMID- 23553834
TI  - Lamprey immunity is far from primitive.

PMID- 23553835
TI  - Rig-I regulates NF-kappaB activity through binding to Nf-kappab1 3'-UTR mRNA.
AB  - Retinoic acid inducible gene I (RIG-I) senses viral RNAs and triggers innate
      antiviral responses through induction of type I IFNs and inflammatory cytokines.
      However, whether RIG-I interacts with host cellular RNA remains undetermined.
      Here we report that Rig-I interacts with multiple cellular mRNAs, especially Nf
      kappab1. Rig-I is required for NF-kappaB activity via regulating Nf-kappab1
      expression at posttranscriptional levels. It interacts with the multiple binding
      sites within 3'-UTR of Nf-kappab1 mRNA. Further analyses reveal that three
      distinct tandem motifs enriched in the 3'-UTR fragments can be recognized by Rig
      I. The 3'-UTR binding with Rig-I plays a critical role in normal translation of
      Nf-kappab1 by recruiting the ribosomal proteins [ribosomal protein L13 (Rpl13)
      and Rpl8] and rRNAs (18S and 28S). Down-regulation of Rig-I or Rpl13
      significantly reduces Nf-kappab1 and 3'-UTR-mediated luciferase expression
      levels. These findings indicate that Rig-I functions as a positive regulator for
      NF-kappaB signaling and is involved in multiple biological processes in addition
      to host antivirus immunity.

PMID- 23553836
TI  - Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and
      frontotemporal dementia causes neurodegeneration.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share
      phenotypic and pathologic overlap. Recently, an expansion of GGGGCC repeats in
      the first intron of C9orf72 was found to be a common cause of both illnesses;
      however, the molecular pathogenesis of this expanded repeat is unknown. Here we
      developed both Drosophila and mammalian models of this expanded hexanucleotide
      repeat and showed that expression of the expanded GGGGCC repeat RNA (rGGGGCC) is
      sufficient to cause neurodegeneration. We further identified Pur alpha as the RNA
      binding protein of rGGGGCC repeats and discovered that Pur alpha and rGGGGCC
      repeats interact in vitro and in vivo in a sequence-specific fashion that is
      conserved between mammals and Drosophila. Furthermore, overexpression of Pur
      alpha in mouse neuronal cells and Drosophila mitigates rGGGGCC repeat-mediated
      neurodegeneration, and Pur alpha forms inclusions in the fly eye expressing
      expanded rGGGGCC repeats, as well as in cerebellum of human carriers of expanded
      GGGGCC repeats. These data suggest that expanded rGGGGCC repeats could sequester
      specific RNA-binding protein from their normal functions, ultimately leading to
      cell death. Taken together, these findings suggest that the expanded rGGGGCC
      repeats could cause neurodegeneration, and that Pur alpha may play a role in the
      pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia.

PMID- 23553837
TI  - Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor
      growth, and metastasis.
AB  - Epidemiological and preclinical evidence supports that omega-3 dietary fatty
      acids (fish oil) reduce the risks of macular degeneration and cancers, but the
      mechanisms by which these omega-3 lipids inhibit angiogenesis and tumorigenesis
      are poorly understood. Here we show that epoxydocosapentaenoic acids (EDPs),
      which are lipid mediators produced by cytochrome P450 epoxygenases from omega-3
      fatty acid docosahexaenoic acid, inhibit VEGF- and fibroblast growth factor 2
      induced angiogenesis in vivo, and suppress endothelial cell migration and
      protease production in vitro via a VEGF receptor 2-dependent mechanism. When EDPs
      (0.05 mg . kg(-1) . d(-1)) are coadministered with a low-dose soluble epoxide
      hydrolase inhibitor, EDPs are stabilized in circulation, causing ~70% inhibition
      of primary tumor growth and metastasis. Contrary to the effects of EDPs, the
      corresponding metabolites derived from omega-6 arachidonic acid,
      epoxyeicosatrienoic acids, increase angiogenesis and tumor progression. These
      results designate epoxyeicosatrienoic acids and EDPs as unique endogenous
      mediators of an angiogenic switch to regulate tumorigenesis and implicate a
      unique mechanistic linkage between omega-3 and omega-6 fatty acids and cancers.

PMID- 23553838
TI  - In situ X-ray studies of adlayer-induced crystal nucleation at the liquid-liquid
      interface.
AB  - Crystal nucleation and growth at a liquid-liquid interface is studied on the
      atomic scale by in situ A-resolution X-ray scattering methods for the case of
      liquid Hg and an electrochemical dilute electrolyte containing Pb(2+), F(-), and
      Br(-) ions. In the regime negative of the Pb amalgamation potential Phi(rp) = 
      0.70 V, no change is observed from the surface-layered structure of pure Hg. Upon
      potential-induced release of Pb(2+) from the Hg bulk at Phi > Phi(rp), the
      formation of an intriguing interface structure is observed, comprising a well
      defined 7.6-A-thick adlayer, decorated with structurally related 3D crystallites.
      Both are identified by their diffraction peaks as PbFBr, preferentially aligned
      with their axis along the interface normal. X-ray reflectivity shows the adlayer
      to consist of a stack of five ionic layers, forming a single-unit-cell-thick
      crystalline PbFBr precursor film, which acts as a template for the subsequent
      quasiepitaxial 3D crystal growth. This growth behavior is assigned to the
      combined action of electrostatic and short-range chemical interactions.

PMID- 23553839
TI  - Funnel metadynamics as accurate binding free-energy method.
AB  - A detailed description of the events ruling ligand/protein interaction and an
      accurate estimation of the drug affinity to its target is of great help in
      speeding drug discovery strategies. We have developed a metadynamics-based
      approach, named funnel metadynamics, that allows the ligand to enhance the
      sampling of the target binding sites and its solvated states. This method leads
      to an efficient characterization of the binding free-energy surface and an
      accurate calculation of the absolute protein-ligand binding free energy. We
      illustrate our protocol in two systems, benzamidine/trypsin and SC
      558/cyclooxygenase 2. In both cases, the X-ray conformation has been found as the
      lowest free-energy pose, and the computed protein-ligand binding free energy in
      good agreement with experiments. Furthermore, funnel metadynamics unveils
      important information about the binding process, such as the presence of
      alternative binding modes and the role of waters. The results achieved at an
      affordable computational cost make funnel metadynamics a valuable method for drug
      discovery and for dealing with a variety of problems in chemistry, physics, and
      material science.

PMID- 23553840
TI  - Increased levels of gene therapy may not be beneficial in retinal disease.

PMID- 23553841
TI  - Overexpressed nuclear BAG-1 in human hepatocellular carcinoma is associated with
      poor prognosis and resistance to doxorubicin.
AB  - Bcl-2-associated athanogene-1 (BAG-1) is a multifunctional anti-apoptotic protein
      which regulates an array of cellular processes, including apoptosis, signaling,
      proliferation, transcription, and cell motility and has been reported to be over
      expressed in a number of human malignancies. To investigate the possible
      involvement of BAG-1 in tumorigenesis of hepatocellular carcinoma (HCC), we
      performed Western blot analysis in eight paired samples of HCC and adjacent
      peritumoral tissues and immunohistochemistry in 65 paraffin sections of HCC,
      which both showed an enhanced expression of nuclear BAG-1 isoform in HCC tissues.
      Statistical analysis confirmed that overexpression of nuclear BAG-1 in HCC
      tissues was significantly associated with histological grading (P < 0.001), poor
      prognosis (P = 0.004), and was found to be an independent prognostic indicator
      for HCC (P = 0.023). We also noted that BAG-1 was overexpressed in four HCC cell
      lines compared with a normal hepatocyte cell line, and BAG-1 overexpression
      increased resistance of HCC cells to doxorubicin, a common chemotherapeutic agent
      for HCC. Furthermore, we observed that knock down of BAG-1 with siRNA in HepG2
      cells increased the chemosensitivity of cells, a process mediated through
      inhibition of doxorubicin-triggered NF-kappaB activation; and knock down of BAG-1
      suppressed proliferation and cell cycle transition of HepG2 cells. In
      consequence, our results for the first time indicated that BAG-1 was dysregulated
      in HCC and suppression of BAG-1 expression which resulted in inhibiting of NF
      kappaB signaling might be developed into a new strategy in HCC therapy.

PMID- 23553842
TI  - Ligand-induced MU opioid receptor internalization in enteric neurons following
      chronic treatment with the opiate fentanyl.
AB  - Morphine differs from most opiates its poor ability to internalize MU opioid
      receptors (MUORs). However, chronic treatment with morphine produces adaptational
      changes at the dynamin level, which enhance the efficiency of acute morphine
      stimulation to promote MUOR internalization in enteric neurons. This study tested
      the effect of chronic treatment with fentanyl, a MUOR-internalizing agonist, on
      ligand-induced endocytosis and the expression of the intracellular trafficking
      proteins, dynamin and beta-arrestin, in enteric neurons using organotypic
      cultures of the guinea pig ileum. In enteric neurons from guinea pigs chronically
      treated with fentanyl, MUOR immunoreactivity was predominantly at the cell
      surface after acute exposure to morphine with a low level of MUOR translocation,
      slightly higher than in neurons from naive animals. This internalization was not
      due to morphine's direct effect, because it was also observed in neurons exposed
      to medium alone. By contrast, D-Ala2-N-Me-Phe4-Gly-ol5-enkephalin (DAMGO), a
      potent MUOR-internalizing agonist, induced pronounced and rapid MUOR endocytosis
      in enteric neurons from animals chronically treated with fentanyl or from naive
      animals. Chronic fentanyl treatment did not alter dynamin or beta-arrestin
      expression. These findings indicate that prolonged activation of MUORs with an
      internalizing agonist such as fentanyl does not enhance the ability of acute
      morphine to trigger MUOR endocytosis or induce changes in intracellular
      trafficking proteins, as observed with prolonged activation of MUORs with a
      poorly internalizing agonist such as morphine. Cellular adaptations induced by
      chronic opiate treatment might be ligand dependent and vary with the agonist
      efficiency to induce receptor internalization.

PMID- 23553846
TI  - EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective
      c-Met inhibitors.
AB  - PURPOSE: The mesenchymal-epithelial transition factor (c-Met) receptor, also
      known as hepatocyte growth factor receptor (HGFR), controls morphogenesis, a
      process that is physiologically required for embryonic development and tissue
      repair. Aberrant c-Met activation is associated with a variety of human
      malignancies including cancers of the lung, kidney, stomach, liver, and brain. In
      this study, we investigated the properties of two novel compounds developed to
      selectively inhibit the c-Met receptor in antitumor therapeutic interventions.
      EXPERIMENTAL DESIGN: The pharmacologic properties, c-Met inhibitory activity, and
      antitumor effects of EMD 1214063 and EMD 1204831 were investigated in vitro and
      in vivo, using human cancer cell lines and mouse xenograft models. RESULTS: EMD
      1214063 and EMD 1204831 selectively suppressed the c-Met receptor tyrosine kinase
      activity. Their inhibitory activity was potent [inhibitory 50% concentration
      (IC50), 3 nmol/L and 9 nmol/L, respectively] and highly selective, when compared
      with their effect on a panel of 242 human kinases. Both EMD 1214063 and EMD
      1204831 inhibited c-Met phosphorylation and downstream signaling in a dose
      dependent fashion, but differed in the duration of their inhibitory activity. In
      murine xenograft models, both compounds induced regression of human tumors,
      regardless of whether c-Met activation was HGF dependent or independent. Both
      drugs were well tolerated and induced no substantial weight loss after more than
      3 weeks of treatment. CONCLUSIONS: Our results indicate selective c-Met
      inhibition by EMD 1214063 and EMD 1204831 and strongly support clinical testing
      of these compounds in the context of molecularly targeted anticancer strategies.

PMID- 23553847
TI  - Reevaluating the accelerated approval process for oncology drugs.
AB  - For a new therapy to qualify for the accelerated approval pathway, it must treat
      a serious disease for which there is "unmet medical need"--defined as providing a
      therapy where none exists or providing a therapy that may be potentially superior
      to existing therapy. The increasing number of available therapies, coupled with
      the lack of accepted endpoints considered "reasonably likely to predict clinical
      benefit" and the lack of clarity early in development about circumstances in
      which a new product will qualify for accelerated approval, is pushing developers
      to pursue accelerated approval in heavily pretreated patients to fulfill an unmet
      need. To optimize the accelerated approval pathway, we propose here a
      reevaluation of what constitutes "unmet medical need" and "available therapy" in
      oncology. We also discuss ways for new endpoints to become qualified for use in
      supporting accelerated approval, and propose a structured process for pursuing
      accelerated approval.

PMID- 23553848
TI  - A dose-ranging study of cabozantinib in men with castration-resistant prostate
      cancer and bone metastases.
AB  - BACKGROUND: Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study
      of cabozantinib (100 mg daily) showed improved bone scans in subjects with
      metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AE)
      caused frequent dose reductions. This study was designed to determine the
      efficacy and tolerability of cabozantinib at lower starting doses. EXPERIMENTAL
      DESIGN: An adaptive design was used to determine the lowest active daily dose
      among 60, 40, and 20 mg. The primary endpoint was week 6 bone scan response,
      defined as >=30% decrease in bone scan lesion area. The secondary endpoint was
      change in circulating tumor cells (CTC). RESULTS: Among 11 evaluable subjects
      enrolled at 40 mg, there were 9 partial responses (PR), 1 complete response, and
      1 stable disease (SD). Of 10 subjects subsequently enrolled at 20 mg, there were
      1 PR, 5 SDs, and 4 with progressive disease. Among 13 subjects enrolled on the 40
      mg expansion cohort, there were 6 PRs and 7 SDs. No subjects required dose
      reduction or treatment interruption at 6 or 12 weeks; 3 subjects at dose level 0
      discontinued due to AEs by 12 weeks. At 40 mg, median treatment duration was 27
      weeks. 58% of subjects with >=5 CTCs/7.5 mL at baseline converted to <5.
      CONCLUSIONS: Cabozantinib 40 mg daily was associated with a high rate of bone
      scan response. Cabozantinib 40 mg daily was associated with better tolerability
      than previously reported for cabozantinib 100 mg daily. These observations
      informed the design of phase III studies of cabozantinib in mCRPC.

PMID- 23553849
TI  - A multicenter phase II study of ganetespib monotherapy in patients with
      genotypically defined advanced non-small cell lung cancer.
AB  - PURPOSE: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a
      chaperone protein critical to tumor growth and proliferation. In this phase II
      study, we evaluated the activity and tolerability of ganetespib in previously
      treated patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN:
      Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no
      EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by
      intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until
      disease progression. The primary endpoint was progression-free survival (PFS) at
      16 weeks. Secondary endpoints included objective response (ORR), duration of
      treatment, tolerability, median PFS, overall survival (OS), and correlative
      studies. RESULTS: Ninety-nine patients with a median of 2 prior systemic
      therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C
      (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively.
      Four patients (4%) achieved partial response (PR); all had disease that harbored
      anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by
      FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naive patients enrolled
      to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse
      events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The
      most common AEs were diarrhea, fatigue, nausea, and anorexia. CONCLUSIONS:
      Ganetespib monotherapy showed a manageable side effect profile as well as
      clinical activity in heavily pretreated patients with advanced NSCLCs,
      particularly in patients with tumors harboring ALK gene rearrangement.

PMID- 23553850
TI  - Evaluation of food effect on pharmacokinetics of vismodegib in advanced solid
      tumor patients.
AB  - PURPOSE: Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor,
      is approved for treatment of advanced basal cell carcinoma (BCC). We conducted a
      pharmacokinetic study of vismodegib in patients with advanced solid tumors to
      explore the effects of food on drug exposure. EXPERIMENTAL DESIGN: In part I,
      patients were randomized to fasting overnight (FO), a high fat meal (HF), or a
      low fat meal (LF) before a single dose of vismodegib 150 mg. Plasma
      concentrations of vismodegib were determined by a validated liquid chromatography
      tandem mass spectrometry assay. Primary endpoints were C(max) and area under the
      curve (AUC(0-168)). In part II, patients randomized to FO or HF in part I took
      vismodegib 150 mg daily after fasting; those randomized to LF took it after a
      meal. Primary endpoints after two weeks were C(max) and AUC(0-24). RESULTS: Sixty
      (22 FO, 20 HF, 18 LF) and 52 (25 fasting, 27 fed) patients were evaluable for
      primary endpoints in parts I and II, respectively. Mean C(max) and AUC(0-168)
      after a single dose were higher in HF than FO patients [ratios of geometric means
      (90% CI) = 1.75 (1.30, 2.34) and 1.74 (1.25, 2.42), respectively]. There were no
      significant differences in C(max) or AUC(0-24) between fasting and fed groups
      after daily dosing. The frequencies of drug-related toxicities were similar in
      both groups. CONCLUSIONS: A HF meal increases plasma exposure to a single dose of
      vismodegib, but there are no pharmacokinetic or safety differences between
      fasting and fed groups at steady-state. Vismodegib may be taken with or without
      food for daily dosing.

PMID- 23553851
TI  - Feature extraction across individual time series observations with spikes using
      wavelet principal component analysis.
AB  - Clinical studies frequently include repeated measurements of individuals, often
      for long periods. We present a methodology for extracting common temporal
      features across a set of individual time series observations. In particular, the
      methodology explores extreme observations within the time series, such as spikes,
      as a possible common temporal phenomenon. Wavelet basis functions are attractive
      in this sense, as they are localized in both time and frequency domains
      simultaneously, allowing for localized feature extraction from a time-varying
      signal. We apply wavelet basis function decomposition of individual time series,
      with corresponding wavelet shrinkage to remove noise. We then extract common
      temporal features using linear principal component analysis on the wavelet
      coefficients, before inverse transformation back to the time domain for clinical
      interpretation. We demonstrate the methodology on a subset of a large fetal
      activity study aiming to identify temporal patterns in fetal movement (FM) count
      data in order to explore formal FM counting as a screening tool for identifying
      fetal compromise and thus preventing adverse birth outcomes.

PMID- 23553853
TI  - Granulocytes of reptilian sauropsids contain beta-defensin-like peptides: a
      comparative ultrastructural survey.
AB  - The ability of lizards to withstand infections after wounding or amputation of
      the tail or limbs has suggested the presence of antimicrobial peptides in their
      tissues. Previous studies on the lizard Anolis carolinensis have identified
      several beta-defensin-like peptides that may potentially be involved in
      protection from infections. The present ultrastructural immunocytochemical study
      has analyzed tissues in different reptilian species in order to localize the
      cellular source of one of the more expressed beta-defensins previously sequenced
      in lizard indicated as AcBD15. Beta-defensin-like immunoreactivity is present in
      some of the larger, nonspecific granules of granulocytes in two lizard species, a
      snake, the tuatara, and a turtle. The ultrastructural study indicates that only
      heterophilic and basophilic granulocytes contain this defensin while other cell
      types from the epidermis, mesenchyme, and dermis, muscles, nerves, cartilage or
      bone are immunonegative. The study further indicates that not all granules in
      reptilian granulocytes contain the beta-defensin peptide, suggesting the presence
      of granules with different content as previously indicated for mammalian
      neutrophilic leucocytes. No immunolabeling was instead observed in granulocytes
      of the alligator and chick using this antibody. The present immunocytochemical
      observations suggest a broad cross-reactivity and conservation of beta-defensin
      like sequence or steric motif across lepidosaurians and likely in turtles while
      archosaurian granulocytes may contain different beta-defensin-like or other
      peptides.

PMID- 23553852
TI  - Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of
      hyperpolarized [2-13C]pyruvate.
AB  - Hyperpolarized [1-(13) C]pyruvate ([1-(13) C]Pyr) has been used to assess
      metabolism in healthy and diseased states, focusing on the downstream labeling of
      lactate (Lac), bicarbonate and alanine. Although hyperpolarized [2-(13) C]Pyr,
      which retains the labeled carbon when Pyr is converted to acetyl-coenzyme A, has
      been used successfully to assess mitochondrial metabolism in the heart, the
      application of [2-(13) C]Pyr in the study of brain metabolism has been limited to
      date, with Lac being the only downstream metabolic product reported previously.
      In this study, single-time-point chemical shift imaging data were acquired from
      rat brain in vivo. [5-(13) C]Glutamate, [1-(13) C]acetylcarnitine and [1-(13)
      C]citrate were detected in addition to resonances from [2-(13) C]Pyr and [2-(13)
      C]Lac. Brain metabolism was further investigated by infusing dichloroacetate,
      which upregulates Pyr flux to acetyl-coenzyme A. After dichloroacetate
      administration, a 40% increase in [5-(13) C]glutamate from 0.014 +/- 0.004 to
      0.020 +/- 0.006 (p = 0.02), primarily from brain, and a trend to higher citrate
      (0.002 +/- 0.001 to 0.004 +/- 0.002) were detected, whereas [1-(13)
      C]acetylcarnitine was increased in peripheral tissues. This study demonstrates,
      for the first time, that hyperpolarized [2-(13) C]Pyr can be used for the in vivo
      investigation of mitochondrial function and tricarboxylic acid cycle metabolism
      in brain.

PMID- 23553854
TI  - Snai1 is important for avian epicardial cell transformation and motility.
AB  - BACKGROUND: Formation of the epicardium requires several cellular processes
      including migration, transformation, invasion, and differentiation in order to
      give rise to fibroblast, smooth muscle, coronary endothelial and myocyte cell
      lineages within the developing myocardium. Snai1 is a zinc finger transcription
      factor that plays an important role in regulating cell survival and fate during
      embryonic development and under pathological conditions. However, its role in
      avian epicardial development has not been examined. RESULTS: Here we show that
      Snai1 is highly expressed in epicardial cells from as early as the proepicardial
      cell stage and its expression is maintained as proepicardial cells migrate and
      spread over the surface of the myocardium and undergo epicardial-to-mesenchymal
      transformation in the generation of epicardial-derived cells. Using multiple in
      vitro assays, we show that Snai1 overexpression in chick explants enhances
      proepicardial cell migration at Hamburger Hamilton Stage (HH St.) 16, and
      epicardial-to-mesenchymal transformation, cell migration, and invasion at HH St.
      24. Further, we demonstrate that Snai1-mediated cell migration requires matrix
      metalloproteinase activity, and MMP15 is sufficient for this process.
      CONCLUSIONS: Together our data provide new insights into the multiple roles that
      Snai1 has in regulating avian epicardial development.

PMID- 23553855
TI  - Management of differentiated thyroid cancer in the presence of resistance to
      thyroid hormone and TSH-secreting adenomas: a report of four cases and review of
      the literature.
AB  - BACKGROUND: An increased or normal serum TSH concentration, despite elevated
      thyroid hormone levels, is observed in resistance to thyroid hormone (RTH) and
      TSH-secreting adenomas (TSHomas). When coexistent with a differentiated thyroid
      cancer (DTC), maintenance of a suppression of TSH is challenging. OBJECTIVES: The
      aim of the study was to discuss the pitfalls arising from the failure to suppress
      TSH secretion in DTC and the strategies for proper treatment of DTC in
      association with RTH and TSHoma. METHODS: Four unusual cases of DTC associated
      with TSHoma (2 cases), RTH (1 case), and an elevated TSH of unknown etiology (1
      case) are presented, and the literature is reviewed. RESULTS: Although a
      persistent mild TSH elevation may not be a risk factor for the development of
      DTC, it represents an important problem during the treatment of DTC. Aggressive
      treatment options should be applied in the proper order to prevent tumor
      recurrence and persistence in the absence of ideal TSH suppression. CONCLUSIONS:
      Although there is no agreed consensus regarding the management of DTC in the
      presence of persistent hyperthyrotropinemia, complete tumor removal followed by
      radioablation and attempts to reduce the serum TSH to the lowest tolerable level
      are recommended. The outcomes in the reported cases have not been unfavorable,
      despite the persistence of nonsuppressed TSH.

PMID- 23553856
TI  - Skeletal muscle abnormalities in girls and adolescents with Turner syndrome.
AB  - CONTEXT: Turner syndrome (TS) is a chromosomal disorder occurring in
      approximately 1 in 2500 live births. Individuals with TS report lower levels of
      physical activity than healthy control (HC) subjects. Cardiorespiratory
      limitations may contribute to the observed reduction in physical activity.
      OBJECTIVE: The objective of this study was to compare muscle metabolism of
      patients with TS vs HC subjects before and after exercise using exercise testing,
      magnetic resonance imaging, and magnetic resonance spectroscopy techniques.
      DESIGN: We hypothesized that girls and adolescents with TS would have muscle
      metabolic abnormalities not present in the HC population. SETTING: The research
      was conducted at the Hospital for Sick Children in Toronto, Ontario, Canada.
      PARTICIPANTS: Fifteen participants with TS were age-, activity-, and body mass
      index Z-score-matched with 16 HC subjects. MAIN OUTCOME MEASURES: (31)P magnetic
      resonance spectroscopy was used to characterize muscle metabolism at rest and
      after 30 seconds of high-intensity exercise, 60 seconds of moderate-intensity
      exercise, and 5 minutes of low-intensity exercise. RESULTS: While achieving the
      same workloads, participants with TS exhibited a greater difference between rest
      and end-exercise pH compared with HC subjects after 30 seconds (TS, 0.29 +/-
      0.04; HC, 0.21 +/- 0.08; P = .03) and 90 seconds (TS, 0.47 +/- 0.22; HC, 0.32 +/-
      0.13; P = .02) of exercise. During the 5-minute exercise test, similar workloads
      were achieved between groups; however, ATP production was greater in participants
      with TS vs the HC subjects via all 3 bioenergetic pathways (total ATP: TS, 0.90
      +/- 0.34; HC, 0.60 +/- 0.25; P = .01). CONCLUSIONS: The results of this study
      suggest that patients with TS exhibit greater anaerobic stress during exercise
      than HC subjects, which may lead to symptoms of increased muscle fatigue with
      short bursts of activity. Recovery metabolism after exercise appears to be
      similar between participants with TS and HC subjects, which is suggestive of
      normal mitochondrial metabolism and oxygen transport.

PMID- 23553857
TI  - Dysregulation of the autonomic nervous system predicts the development of the
      metabolic syndrome.
AB  - CONTEXT: Stress is suggested to lead to metabolic dysregulations as clustered in
      the metabolic syndrome. Although dysregulation of the autonomic nervous system is
      found to associate with the metabolic syndrome and its dysregulations, no
      longitudinal study has been performed to date to examine the predictive value of
      this stress system in the development of the metabolic syndrome. OBJECTIVE: We
      examined whether autonomic nervous system functioning predicts 2-year development
      of metabolic abnormalities that constitute the metabolic syndrome. DESIGN: Data
      of the baseline and 2-year follow-up assessment of a prospective cohort: the
      Netherlands Study of Depression and Anxiety was used. SETTING: Participants were
      recruited in the general community, primary care, and specialized mental health
      care organizations. PARTICIPANTS: A group of 1933 participants aged 18-65 years.
      MAIN OUTCOME MEASURES: The autonomic nervous system measures included heart rate
      (HR), respiratory sinus arrhythmia (RSA; high RSA reflecting high parasympathetic
      activity), pre-ejection period (PEP; high PEP reflecting low sympathetic
      activity), cardiac autonomic balance (CAB), and cardiac autonomic regulation
      (CAR). Metabolic syndrome was based on the updated Adult Treatment Panel III
      criteria and included high waist circumference, serum triglycerides, blood
      pressure, serum glucose, and low high-density lipoprotein (HDL) cholesterol.
      RESULTS: Baseline short PEP, low CAB, high HR, and CAR were predictors of an
      increase in the number of components of the metabolic syndrome during follow-up.
      High HR and low CAB were predictors of a 2-year decrease in HDL cholesterol, and
      2-year increase in diastolic and systolic blood pressure. Short PEP and high CAR
      also predicted a 2-year increase in systolic blood pressure, and short PEP
      additionally predicted 2-year increase in diastolic blood pressure. Finally, a
      low baseline RSA was predictive for subsequent decreases in HDL cholesterol.
      CONCLUSION: Increased sympathetic activity predicts an increase in metabolic
      abnormalities over time. These findings suggest that a dysregulation of the
      autonomic nervous system is an important predictor of cardiovascular diseases and
      diabetes through dysregulating lipid metabolism and blood pressure over time.

PMID- 23553858
TI  - Increased fracture risk and osteoporosis not associated with vitamin D levels in
      Malaysian patients with inflammatory bowel disease.
AB  - INTRODUCTION: Osteoporosis and osteopenia are well-recognized complications of
      inflammatory bowel disease. Previous studies have suggested that vitamin D
      deficiency is an important risk factor for the development of osteoporosis. We
      hypothesized that low vitamin D levels is the main reason for reduced bone
      mineral density in patients with inflammatory bowel disease. We aimed to study
      its potential role in Malaysia, which is a tropical country with 3 large ethnic
      groups. We also sought to examine the relationship between fracture risk and bone
      mineral density in this group. METHODOLOGY: Relevant history as well as 25
      hydroxycholecalciferol (vitamin D) levels and bone mineral density were obtained.
      Normal, inadequate, and low vitamin D levels were defined as 61-160 nmol/L (24-64
      ng/mL), 30-60 nmol/L (12-24 ng/mL), and less than 30 nmol/L (<12 ng/mL),
      respectively. RESULTS: Seventy-two patients were recruited. The prevalence of
      osteopenia and osteoporosis, respectively, were 58% and 17% in the spine and 51%
      and 14% in the hip. Mean vitamin D level in the group was low at 45.12 +/- 17.4
      nmol/L (18.05 +/- 6.96 ng/mL), but there was no significant association between
      bone mineral density and vitamin D level. Twelve patients (16.7%) had a fragility
      fracture after the diagnosis of inflammatory bowel disease. The cumulative
      fracture incidence was 10% at 5 years and 35% at 10 years. There was a
      statistically significant association between osteoporosis of hip and a history
      of fracture (odds ratio 5.889; 95% confidence interval 1.41-24.53, P = .009).
      CONCLUSION: Osteoporosis is prevalent among Malaysian patients with inflammatory
      bowel disease and is associated with a 6-fold increased risk of fractures. Most
      inflammatory bowel disease patients had inadequate or low vitamin D levels, but
      there was no association between vitamin D levels and BMD.

PMID- 23553859
TI  - Hyperinsulinemia and urinary calcium excretion in calcium stone formers with
      idiopathic hypercalciuria.
AB  - CONTEXT: Calcium stone formers with idiopathic hypercalciuria (IH) are known to
      exhibit an exaggerated postprandial rise in urine calcium excretion compared with
      non-stone-forming individuals, and insulin has been proposed to mediate this
      difference. OBJECTIVE: Our objective was to investigate the impact of
      hyperinsulinemia on urine calcium excretion in IH compared with non-stone-forming
      controls. PARTICIPANTS AND SETTING: Ten IH patients and 22 control non-stone
      forming subjects (8 lean and 14 overweight and obese) participated at the
      University of Texas Southwestern Clinical and Translational Research Center.
      DESIGN: After stabilization on a fixed metabolic diet, subjects underwent a
      hyperinsulinemic-euglycemic clamp. Fasting 2-hour urine specimens were collected
      before and during the clamp. MAIN OUTCOME MEASURES: Changes in fractional calcium
      excretion (F(E)Ca) during the clamp were compared between the 3 groups of
      subjects (IH, overweight/obese controls, and lean controls). Insulin sensitivity
      was measured by glucose disposal rate. RESULTS: IH had significantly higher 24
      hour urine calcium excretion than controls, and exhibited similar age, body mass
      index, and insulin sensitivity as overweight/obese controls. The hyperinsulinemic
      euglycemic clamp resulted in a significant increase in serum insulin with no
      significant changes in serum calcium and glucose. This was accompanied by a small
      increase in F(E)Ca, with no significant differences between the 3 groups. There
      was no correlation between insulin sensitivity and 24-hour urine calcium or the
      change in F(E)Ca during the hyperinsulinemic clamp. CONCLUSIONS: The rise in
      urine calcium associated with euglycemic hyperinsulinemia was small and not
      statistically different between IH and non-stone-forming controls. Insulin is
      therefore unlikely to play a significant pathogenetic role in IH.

PMID- 23553860
TI  - Vertebral bone marrow fat associated with lower trabecular BMD and prevalent
      vertebral fracture in older adults.
AB  - CONTEXT: Bone marrow fat (BMF) and bone mineral density (BMD) by dual x-ray
      energy absorptiometry (DXA) are negatively correlated. However, little is known
      about the association of BMF with fracture or with separate trabecular and
      cortical bone compartments. OBJECTIVE: Our objective was to assess the
      relationships between vertebral BMF, BMD by quantitative computed tomography, and
      fracture in older adults. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross
      sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort. MAIN
      OUTCOME MEASURES: Outcomes measures included vertebral BMF (L1-L4) measured with
      magnetic resonance spectroscopy, quantitative computed tomography and DXA scans
      of the hip and spine, and DXA vertebral fracture assessments. Previous clinical
      fracture was determined from medical records. RESULTS: In 257 participants
      without recent bone-active medication use, mean age was 79 (SD 3.1) years. Mean
      BMF was 53.5% +/- 8.1% in men and 55.0% +/- 8.4% in women. Those with prevalent
      vertebral fracture (21 men, 32 women) had higher mean BMF in models adjusted for
      BMD. In separate models by sex, the difference was statistically significant only
      in men (57.3% vs 52.8%, P = 0.02). BMF was associated with lower trabecular
      volumetric BMD (vBMD) at the spine (-10.5% difference for each 1 SD increase in
      BMF, P < 0.01), total hip, and femoral neck, but not with cortical vBMD, in
      women. In men, BMF was marginally associated with trabecular spine vBMD (-6.1%, P
      = 0.05). Total hip and spine areal BMD (aBMD) were negatively correlated with BMF
      in women only. CONCLUSION: Higher marrow fat correlated with lower trabecular,
      but not cortical, BMD in older women but not men. Higher marrow fat was
      associated with prevalent vertebral fracture in men, even after adjustment for
      BMD.

PMID- 23553861
TI  - Induction of the neurokinin 1 receptor by TNFalpha in endometriotic tissue
      provides the potential for neurogenic control over endometriotic lesion growth.
AB  - CONTEXT: Endometriosis is characterized by the growth of ectopic endometrial
      tissue. Nerve fibers are frequently associated with ectopic lesions, and
      neurogenic inflammation may play a role in endometriosis. OBJECTIVE: The purpose
      of this study was to determine the presence of tachykinin receptors in
      endometriotic lesions and the role of TNFalpha on their expression. DESIGN: This
      study was an assessment of matching eutopic and ectopic endometrial tissue and
      peritoneal fluid from patients with endometriosis and an in vitro analysis of
      primary endometrial cells. SETTING: The setting was a university hospital.
      PATIENTS: Participants were premenopausal women undergoing laparoscopy.
      INTERVENTIONS: Endometriotic lesions were removed surgically. MAIN OUTCOME
      MEASURES: Tachykinin mRNA (TACR1/2) and protein (neurokinin 1 receptor [NK1R])
      expression in both eutopic and ectopic endometrial tissue from patients with
      endometriosis and the correlation to peritoneal fluid TNFalpha were measured.
      Primary endometrial epithelial and stromal cells were assessed in vitro to
      determine the induction of TACR1/2 and NK1R expression after TNFalpha treatment.
      Cell viability of endometrial stromal cells after substance P exposure was also
      assessed. RESULTS: Expression of both TACR1 and TACR2 mRNA was significantly
      higher in the ectopic than in the eutopic tissue. Both TACR1 mRNA and NK1R
      protein expression was significantly correlated with peritoneal fluid TNFalpha,
      and in vitro studies confirmed that TNFalpha treatment induced both TACR1 mRNA
      and NK1R protein expression in endometrial stromal cells. In endometrial stromal
      cells, substance P treatment enhanced cell viability, which was inhibited by a
      specific NK1R antagonist. CONCLUSIONS: NK1R expression is induced in ectopic
      endometrial tissue by peritoneal TNFalpha. Induction of NK1R expression may
      permit endometriotic lesion maintenance via exposure to substance P.

PMID- 23553862
TI  - The lateralization accuracy of inferior petrosal sinus sampling in 501 patients
      with Cushing's disease.
AB  - CONTEXT: It is often difficult to find an adenoma in patients with Cushing's
      disease (CD) whose preoperative magnetic resonance imaging (MRI) is normal.
      Better localizing modalities are needed. OBJECTIVE: The aim of this study was to
      determine the accuracy of inferior petrosal sinus sampling (IPSS) in predicting
      adenoma lateralization. DESIGN AND SETTING: We conducted a prospective
      observational study at a tertiary care clinical research center. PATIENTS: A
      total of 501 consecutive patients (363 female) with confirmed ACTH adenomas and
      IPSS were included. MAIN OUTCOME MEASURE: We measured the accuracy of IPSS to
      predict the intrasellar location of an adenoma. RESULTS: IPSS confirmed a
      pituitary source of ACTH secretion in 491 patients (98%). All 10 patients with
      false-negative results had peak IPSS ACTH concentrations (before or after CRH) of
      < 400 pg/ml. Interpetrosal (side-to-side) ratios were >= 1.4 in 491 patients
      (98%). This ratio correctly predicted lateralization in 273 of 396 patients
      (positive predictive value = 69%) with a lateral adenoma. Left-sided IPSS
      lateralization (P = .008) and consistent lateralization before and after CRH
      administration (P = .02) were associated with enhanced accuracy. When positive,
      preoperative MRI correlated with adenoma location in 171 of 201 patients
      (positive predictive value = 86%). CONCLUSIONS: Potential false-negative results,
      the most common type of diagnostic error with IPSS for the differential diagnosis
      of CS, can be identified by peak IPSS ACTH values < 400 pg/ml. When MRI is
      normal, IPSS can be used to guide surgical exploration in patients with negative
      preoperative imaging. However, because of the limited accuracy of lateralization,
      thorough exploration of the pituitary gland is required when an adenoma is not
      readily discovered based on predicted location.

PMID- 23553863
TI  - The effects of long-term valsartan treatment on skeletal muscle fatty acid
      handling in humans with impaired glucose metabolism.
AB  - CONTEXT: Blocking the renin-angiotensin system reduces the incidence of type 2
      diabetes mellitus in humans with impaired glucose metabolism (IGM). Nevertheless,
      underlying mechanisms remain to be established. OBJECTIVE: The purpose of this
      study was to investigate the effects of the angiotensin II type 1 receptor
      blocker valsartan (VAL) on skeletal muscle fatty acid (FA) handling in subjects
      with IGM. DESIGN/SETTING: This was a randomized, double-blind placebo-controlled
      trial at Maastricht University Medical Center. INTERVENTION/MAIN
      OUTCOMES/PARTICIPANTS: Fasting and postprandial skeletal muscle FA handling were
      assessed at baseline and after 26 weeks of treatment with VAL or placebo in 26
      subjects with IGM. Fasting and postprandial skeletal muscle FA handling were
      determined by combining the forearm balance technique with stable isotopes of
      palmitate. [2H2]-Palmitate was infused iv to label endogenous triacylglycerol
      (TAG) and free fatty acid (FFA) in the circulation, and [U-13C]-palmitate was
      incorporated in a high-fat mixed meal (2.6 MJ, 61% energy from fat) to label
      chylomicron TAG. Muscle biopsy samples were taken to determine im TAG,
      diacylglycerol (DAG), FFA, and phospholipid contents, their fractional synthetic
      rates and degree of saturation, and mRNA expression of oxidative genes. RESULTS:
      VAL decreased saturation of im TAG and DAG fractions but did not affect net
      muscle uptake of [2H2]-palmitate, very low-density lipoprotein ([2H2])-TAG and
      chylomicron ([U-13C])-TAG, and muscle mRNA expression. VAL decreased FA
      spillover, as estimated by circulating [U-13C]-palmitate, and FFA rate of
      appearance and tended to decrease chylomicron TAG concentrations. CONCLUSIONS:
      VAL treatment for 26 weeks decreased saturation of skeletal muscle TAG and DAG
      stores, suggesting altered intramuscular lipid partitioning of FA. The VAL
      induced reduction in postprandial FA spillover, endogenous lipolysis, and
      chylomicron TAG concentrations indicate improved adipose tissue lipid buffering
      capacity.

PMID- 23553864
TI  - A case of primary hyperparathyroidism due to ectopic parathyroid adenoma in the
      thymus, accompanied with vitamin D deficiency.
AB  - INTRODUCTION: Primary hyperparathyroidism (PHPT) caused by ectopic parathyroid
      adenoma (EPA) is not rare, whereas the concurrence of PHPT and vitamin D
      deficiency (VDD) in youth is uncommon. We reported a case of PHPT with EPA in the
      thymus, accompanied by a very low level of 25-hydroxyvitamin D. CASE REPORT: A 20
      year-old man suffered from bilateral hip fractures under slight force or no
      force. Biochemical findings were consistent with PHPT and VDD. Examination
      results showed severe osteoporosis; both technetium-99m-sestamibi scintigraphy
      and computed tomography showed an abnormal nodule in the mediastinum, which was
      resected with a thoracoscope and confirmed pathologically as an EPA in the
      thymus. Hypocalcemia due to hungry bone syndrome (HBS) occurred after surgery and
      was resolved quickly with large-dose calcium and alfacalcidol supplementation.
      DISCUSSION: PHPT is usually a sporadic disease, and VDD is unfortunately a common
      global problem. Negative family history and no concomitant illness seemed to rule
      out familiar hyperparathyroidism. VDD with no gastrointestinal symptom and
      nutritional anemia was caused by long-term inadequate sun exposure before the
      first fracture and a 2-year absence of sun exposure due to immobilization. Both
      PHPT and VDD contributed to severe osteoporosis, which could be exacerbated by
      not attaining his peak bone mass and by immobilization because of a fragile
      fracture with delayed healing. Large parathyroid adenoma, VDD, overt bone
      disease, and PTH resistance in the patient were related to postoperative hungry
      bone syndrome. CONCLUSION: Any fracture in young adults that has not healed
      within 3 months should alert physicians to search for some factors or underlying
      diseases.

PMID- 23553865
TI  - An independent positive relationship between the serum total osteocalcin level
      and fat-free mass in healthy premenopausal women.
AB  - CONTEXT: It is widely reported that osteocalcin is negatively associated with fat
      mass. However, there are few reports describing its correlation with fat-free
      mass, particularly in women. OBJECTIVES: The objective of the current study was
      to investigate the possible relationship between osteocalcin and fat-free mass in
      healthy, nonobese women. DESIGN AND SETTING: This study was performed in a
      tertiary university teaching hospital. SUBJECTS: A total of 504 healthy women
      aged 20-75 years were enrolled. MAIN OUTCOME MEASURES: Body composition was
      measured using a bioelectronics impedance analyzer. The serum concentrations of
      total osteocalcin, estradiol, leptin, osteoprotegerin, the receptor activator of
      nuclear factor-kappaB ligand, IGF-I, fasting plasma glucose, and urinary N
      terminal telopeptide of type I collagen were tested. The bone mineral densities
      (BMDs) at the lumbar spine and proximal femoral neck were measured by dual-energy
      X-ray absorptiometry. RESULTS: The serum total osteocalcin level had a
      significant positive association with fat-free mass (r = 0.168, P = .007) after
      adjusting for age, fat mass, menopausal status, estradiol, fasting glucose,
      leptin, osteoprotegerin, receptor activator of nuclear factor-kappaB ligand, IGF
      I, N-terminal telopeptide of type I collagen, BMDs, and waist and hip
      circumference. Analysis in pre- and postmenopausal women demonstrated that this
      association was only present in premenopausal women (r = 0.190, P = .005). The
      multiple stepwise regression analysis revealed that hip circumference, femoral
      neck-BMD, fat mass, leptin, osteocalcin, and age are the contributors to the
      changes in fat-free mass in premenopausal women (adjusted R(2) = 0.521, P <
      .001). CONCLUSION: The serum level of total osteocalcin was positively associated
      with fat-free mass independent of age, fat mass, leptin, and other confounders in
      premenopausal women.

PMID- 23553866
TI  - Low-dose fluoride in postmenopausal women: a randomized controlled trial.
AB  - CONTEXT: Trials of high-dose fluoride have reported increased bone formation and
      bone mineral density (BMD), but impaired bone mineralization and either adverse
      or neutral effects on fracture risk. Meta-analysis of a heterogeneous dataset of
      small trials suggests that daily doses of <20 mg fluoride might reduce fracture
      risk, but it is not known whether low doses of fluoride are safely anabolic to
      bone. OBJECTIVE: We set out to investigate the skeletal effects of low doses of
      fluoride. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo
      controlled randomized trial over 1 year at an academic research center, in 180
      postmenopausal women with osteopenia. INTERVENTION: Participants received daily
      treatment with tablets containing placebo, 2.5 mg fluoride, 5 mg fluoride, or 10
      mg fluoride. MAIN OUTCOME MEASURES: The primary endpoint was a change in lumbar
      spine BMD at 1 year; secondary endpoints were hip and forearm BMD, and markers of
      bone turnover. Safety was assessed by histomorphometric analysis of transiliac
      bone biopsies from a subset of participants. RESULTS: Compared to placebo, none
      of the doses of fluoride altered BMD at any site. The bone formation marker,
      procollagen type I N-terminal propeptide, increased significantly in the 5 mg and
      10 mg fluoride groups compared to placebo (P = .04 and .005, respectively). No
      differences were observed between placebo and any of the fluoride groups in
      levels of beta-C-terminal telopeptide of type I collagen. CONCLUSIONS: Low-dose
      fluoride does not induce substantial effects on surrogates of skeletal health and
      is unlikely to be an effective therapy for osteoporosis.

PMID- 23553867
TI  - Catalytic asymmetric construction of quaternary alpha-amino acid containing
      pyrrolidines through 1,3-dipolar cycloaddition of azomethine ylides to alpha
      aminoacrylates.
AB  - The first catalytic enantioselective 1,3-dipolar cycloaddition of azomethine
      ylides to alpha-aminoacrylate catalyzed by a AgOAc/ferrocenyl oxazolinylphosphine
      (FOXAP) system was developed, which exhibits excellent exo- and
      enantioselectivity (92-99 % ee). This process provides efficient access to useful
      4-aminopyrrolidine-2,4-dicarboxylic acid (APDC)-like compounds containing a
      unique quaternary alpha-amino acid unit.

PMID- 23553868
TI  - Empowering elderly women with osteoarthritis through hands-on exploration of
      adaptive equipment concepts.
AB  - The study investigated the participation experiences of elderly women with hand
      limitations in a maketools-inspired activity for improving bottle openability and
      verified the usefulness of the results from this approach. Participatory design
      was used to stimulate participants' hands-on fabrication of new bottle lid
      concepts. Air-dry modeling clay, Crayola Model Magic(r) (Crayola LLC, 1100 Church
      Lane Easton, PA 18044-0431), clay modeling tools sets and empty bottles were the
      tools used to explore feasible and user-envisioned ideal lids that could
      potentially reduce hand pain and improve function when opening bottles. Twenty
      five elderly women fully participated in the study. They generated 36 bottle lid
      design concepts. Qualitative analysis identified inclusion of four primary design
      features as follows: 1) surface texture; 2) increased leverage through lid shape
      or diameters; 3) increased contact surface with palm/fingers through lid shape or
      height; and 4) facilitation of alternative grip types. The major limitations of
      the study were inclusion of only women participants and healthier persons living
      in a retirement community. Future research is needed to investigate the bottle
      lid preferences of men and persons with more severe hand function living in
      places other than independent living communities.

PMID- 23553869
TI  - Antihypertensive drugs and the risk of congenital anomalies.
AB  - STUDY OBJECTIVE: To estimate the prevalence of congenital anomalies among the
      offspring of women exposed and unexposed to antihypertensive drugs during early
      pregnancy. DESIGN: Matched cohort study. DATABASE: The United Kingdom's General
      Practice Research Database. SUBJECTS: Women exposed to antihypertensive drugs
      during early pregnancy and a sample of matched unexposed pregnant women.
      MEASUREMENTS AND MAIN RESULTS: The prevalence of any anomaly among unexposed and
      exposed women was 23.5 (95% confidence interval [CI] 14.4-38.3) and 20.9 (95% CI
      10.0-43.8) per 1000 pregnancies, respectively (relative risk [RR] 0.9, 95% CI 0.4
      2.2). The relative risk of limb anomalies among women exposed to beta-blockers
      was 6.4 (95% CI 0.6-70.1). Exposure to angiotensin-converting enzyme (ACE)
      inhibitors, beta-blockers, and calcium channel blockers increased the risk of
      genital anomalies (RR 3.8, 95% CI 0.9-16.0; RR 2.8, 95% CI 0.7-11.9; RR 1.3, 95%
      CI 0.1-12.4, respectively). CONCLUSION: ACE inhibitors prescribed in the first
      trimester of pregnancy appeared to increase the risk of congenital anomalies
      among the offspring of exposed women (RR 2.5, 95% CI 0.5-13.5). These drugs
      should be avoided in women planning to become pregnant. A marginally increased
      risk was also found with exposure to beta-blockers (RR 1.4, 95% CI 0.6-3.3).
      These findings are based on small numbers and are not statistically significant.

PMID- 23553870
TI  - Corneal endothelial cell fate is maintained by LGR5 through the regulation of
      hedgehog and Wnt pathway.
AB  - Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a target of
      Wnt signaling, is reportedly a marker of intestine, stomach, and hair follicle
      stem cells in mice. To gain a novel insight into the role of LGR5 in human
      corneal tissue, we performed gain- and loss-of-function studies. The findings of
      this study show for the first time that LGR5 is uniquely expressed in the
      peripheral region of human corneal endothelial cells (CECs) and that LGR5((+))
      cells have some stem/progenitor cell characteristics, and that in human corneal
      endothelium, LGR5 is the target molecule and negative feedback regulator of the
      Hedgehog (HH) signaling pathway. Interestingly, the findings of this study show
      that persistent LGR5 expression maintained endothelial cell phenotypes and
      inhibited mesenchymal transformation (MT) through the Wnt pathway. Moreover, R
      spondin-1, an LGR5 ligand, dramatically accelerated CEC proliferation and also
      inhibited MT through the Wnt pathway. These findings provide new insights into
      the underlying homeostatic regulation of human corneal endothelial
      stem/progenitor cells by LGR5 through the HH and Wnt pathways.

PMID- 23553871
TI  - Closing the yield gap could reduce projected greenhouse gas emissions: a case
      study of maize production in China.
AB  - Although the goal of doubling food demand while simultaneously reducing
      agricultural environmental damage has become widely accepted, the dominant
      agricultural paradigm still considers high yields and reduced greenhouse gas
      (GHG) intensity to be in conflict with one another. Here, we achieved an increase
      in maize yield of 70% in on-farm experiments by closing the yield gap and
      evaluated the trade-off between grain yield, nitrogen (N) fertilizer use, and GHG
      emissions. Based on two groups of N application experiments in six locations for
      16 on-farm site-years, an integrated soil-crop system (HY) approach achieved 93%
      of the yield potential and averaged 14.8 Mg ha(-1) maize grain yield at 15.5%
      moisture. This is 70% higher than current crop (CC) management. More importantly,
      the optimal N rate for the HY system was 250 kg N ha(-1) , which is only 38% more
      N fertilizer input than that applied in the CC system. Both the N2 O emission
      intensity and GHG intensity increased exponentially as the N application rate
      increased, and the response curve for the CC system was always higher than that
      for the HY system. Although the N application rate increased by 38%, N2 O
      emission intensity and the GHG intensity of the HY system were reduced by 12% and
      19%, respectively. These on-farm observations indicate that closing the yield gap
      alongside efficient N management should therefore be prominent among a portfolio
      of strategies to meet food demand while reducing GHG intensity at the same time. 

PMID- 23553875
TI  - Copper-chaperones with dicoordinated Cu(I)--unique protection mechanism.
AB  - Cu(I) dicoordination with thiolate ligands is not common. Yet, different from its
      homologue proteins, human copper chaperone is known to bind Cu(I) using this low
      coordination number while binding Cu(I) only via the two conserved Cysteine
      residues, Cys12 and Cys15. Based on structural analysis, this work determines
      that the protein possesses two distinct conformations referred to as "in" and
      "out" due to the relative positioning of Cys12 (one of Cu(I) binding residues).
      The "out" conformation, with Cys12 pointing out, imposes a buried Cu(I) position,
      whereas the "in" conformation with Cys12 pointing inwards results in a more
      exposed Cu(I) thus, available for transfer. Using QM/MM methods along with
      thermodynamic cycles these two conformations are shown to exhibit different
      coordination preference, suggesting that the protein has evolved to have a unique
      Cu(I) protection mechanism. It is proposed that the "out" conformation with a
      preference to dicoordination prevents Cu(I) interaction with external ligands
      and/or Cu(I) release to the solvent, whereas the "in" conformation with
      preference to tricoordinated Cu(I), facilitates Cu(I) transfer to target
      proteins, where additional ligands are involved.

PMID- 23553876
TI  - Harnessing electron transfer from the perchlorotriphenylmethide anion to
      Y@C82(C(2v)) to engineer an endometallofullerene-based salt.
AB  - We show that electron transfer from the perchlorotriphenylmethide anion (PTM(-))
      to Y@C82(C2v) is an instantaneous process, suggesting potential applications for
      using PTM(-) to perform redox titrations of numerous endohedral
      metallofullerenes. The first representative of a Y@C82-based salt containing the
      complex cation was prepared by treating Y@C82(C2v) with the [K(+)([18]crown
      6)]PTM(-) salt. The synthesis developed involves the use of the [K(+)([18]crown
      6)]PTM(-) salt as a provider of both a complex cation and an electron-donating
      anion that is able to reduce Y@C82 C2v). For the first time, the molar absorption
      coefficients for neutral and anionic forms of the pure isomer of Y@C82(C2v) were
      determined in organic solvents with significantly different polarities.

PMID- 23553877
TI  - Arene CH-O hydrogen bonding: a stereocontrolling tool in palladium-catalyzed
      arylation and vinylation of ketones.

PMID- 23553878
TI  - Realizing the potential of gene-based molecular therapies in bone repair.
AB  - A better understanding of osteogenesis at genetic and biochemical levels is
      yielding new molecular entities that can modulate bone regeneration and
      potentially act as novel therapies in a clinical setting. These new entities are
      motivating alternative approaches for bone repair by utilizing DNA-derived
      expression systems, as well as RNA-based regulatory molecules controlling the
      fate of cells involved in osteogenesis. These sophisticated mediators of
      osteogenesis, however, pose unique delivery challenges that are not obvious in
      deployment of conventional therapeutic agents. Viral and nonviral delivery
      systems are actively pursued in preclinical animal models to realize the
      potential of the gene-based medicines. This article will summarize promising bone
      inducing molecular agents on the horizon as well as provide a critical review of
      delivery systems employed for their administration. Special attention was paid to
      synthetic (nonviral) delivery systems because they are more likely to be adopted
      for clinical testing because of safety considerations. We present a comparative
      analysis of dose-response relationships, as well as pharmacokinetic and
      pharmacodynamic features of various approaches, with the purpose of clearly
      defining the current frontier in the field. We conclude with the authors'
      perspective on the future of gene-based therapy of bone defects, articulating
      promising research avenues to advance the field of clinical bone repair.

PMID- 23553879
TI  - A method for structure analysis of nanomaterials by electron diffraction: phase
      identification and unit cell determination.
AB  - We report a quick and easy method for a random selected area electron diffraction
      (SAED) pattern without rotating and tilting the specimen to perform phase
      identification and unit cell determination by combined with the XRD softwares. If
      your TEM is well aligned and camera length is carefully corrected, two
      dimensional (2D)-SAED pattern can be directly transformed to 1D-profile after the
      center determination of pattern, this profile is then imported to XRD analysis
      packages. Finally, phase identification and unit cell determination can be
      performed after peak search or precise peak position determined by profile
      fitting. Two examples, flaky-like TiO2 nanomaterial and TiO2 nanotubes
      precipitated by the silver nanoparticles, were tested and verified for the
      validation of phase identification and unit cell determination using this method;
      the successful crystallographic analysis of one single gold nanocrystal indicates
      it is still validate for the nanocrystals with the smaller diffraction volume,
      but need two or more random tilt SAED patterns. This method could be further used
      in the quantitative phase analysis, structure determination and Rietveld
      refinement for the nanomaterials if the reliable integrated intensity can be
      extracted.

PMID- 23553880
TI  - How to encourage compassion.

PMID- 23553882
TI  - Shorter life expectancies in eastern versus western Europe.

PMID- 23553881
TI  - Paperless records are not in the best interest of every patient.

PMID- 23553883
TI  - Miravirsen works against hepatitis C virus.

PMID- 23553884
TI  - Chelation therapy may improve cardiovascular health.

PMID- 23553885
TI  - Implementation of the health and social care act.

PMID- 23553886
TI  - Hospitals plant trees to mark second NHS sustainability day.

PMID- 23553887
TI  - Tunable 3D extended self-assembled gold metamaterials with enhanced light
      transmission.
AB  - The optical properties of metamaterials made by block copolymer self-assembly are
      tuned by structural and environmental variations. The plasma frequency red-shifts
      with increasing lattice constant and blue-shifts as the network filling fraction
      increases. Infiltration with dielectric liquids leads also to a red-shift of the
      plasma edge. A 300 nm-thick slab of gyroid-structured gold has a remarkable
      transmission of 20%.

PMID- 23553888
TI  - Gender differences in long-term outcome after primary percutaneous intervention
      for ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Previous studies on gender differences in outcome in patients with ST
      segment elevation myocardial infarction (STEMI) have been performed, but most of
      those are from before the current era of PCI technique and medical therapy and
      have a short duration of follow-up. The objective of our study is to assess the
      influence of gender on long-term outcome in patients with STEMI who underwent
      primary percutaneous intervention (PCI) between January 2006 and May 2008.
      METHODS: Two-year follow-up data from 202 female and 668 male patients undergoing
      primary PCI for STEMI were available from the DEBATER (A Comparison of Drug
      Eluting and Bare Metal Stents for Primary Percutaneous Coronary Intervention with
      or without Abciximab in ST-segment elevation Myocardial Infarction: The Eindhoven
      Reperfusion Study) trial database. The primary endpoint was major adverse cardiac
      events (MACE), defined as the composite of death, myocardial infarction, and
      target vessel revascularization. RESULTS: Women were older (64.7 +/- 11.7 vs.
      59.0 +/- 10.7; P < 0.001), and had more often diabetes mellitus (15% vs. 9%; P =
      0.01) and hypertension (44% vs. 25%; P < 0.001). At two years, the rate of MACE
      was significantly higher in women (21% vs. 14%; P = 0.02). The mortality rate in
      women was 8% versus 2.6% in men (P < 0.001). However, multivariate analysis after
      adjustment for age and the baseline characteristics hypertension, smoking,
      diabetes mellitus, stent diameter, and time between onset of symptoms and arrival
      of the ambulance showed similar MACE and mortality rates in men and women.
      CONCLUSION: Women have higher rates of both MACE and mortality after primary PCI
      for STEMI compared to men because of higher age with higher baseline risk
      profiles.

PMID- 23553889
TI  - Hyperglycemia magnifies bupivacaine-induced cell apoptosis triggered by
      mitochondria dysfunction and endoplasmic reticulum stress.
AB  - Nerve cell injury associated with apoptosis plays an important role in the
      development of diabetic peripheral neuropathy (DPN). However, it remains unclear
      whether preexisting or potential neurocyte damage induced by hyperglycemia
      increases sensitivity to local anesthetics. SH-SY5Y cells were pretreated with a
      high concentration of glucose in vitro, to imitate DPN prior to administration of
      bupivacaine or placebo. Cell viability and apoptosis were investigated with a CCK
      8 assay and flow cytometry, respectively. In addition, mitochondrial membrane
      potential, reactive oxygen species (ROS), mitochondrially generated ROS, and
      activity of mitochondrial complexes I and III were studied to explore the
      molecular mechanism of bupivacaine-induced mitochondrial injury. Grp78 and
      caspase-12 expression were measured by qRT-PCR and Western blot, representing
      endoplasmic reticulum (ER) stress. Cell structure was also assessed via
      transmission electron microscopy. Incubation with bupivacaine decreased the
      activity of mitochondrial complexes I and III; increased ROS production at cell
      and mitochondrial levels, mitochondrial potential depolarization, and Grp78 and
      caspase-12 expression at both transcription and translation levels; and affected
      cell structure, which could be enhanced by glucose pretreatment. These findings
      indicate that mitochondrial dysfunction and ER stress related to ROS are involved
      in bupivacaine-induced apoptosis and may be enhanced by glucose administration.

PMID- 23553890
TI  - Micromotions at the taper interface between stem and neck adapter of a bimodular
      hip prosthesis during activities of daily living.
AB  - The stem-neck taper interface of bimodular hip endoprostheses bears the risk of
      micromotions that can result in ongoing corrosion due to removal of the passive
      layer and ultimately cause implant fracture. We investigated the extent of
      micromotions at the stem-neck interface and the seating behavior of necks of one
      design made from different alloys during daily activities. Modular hip prostheses
      (n = 36, Metha(r), Aesculap AG, Germany) with neck adapters (CoCr29Mo6 or
      Ti6Al4V) were embedded in PMMA (ISO 7206-4) and exposed to cyclic loading with
      peak loads ranging from walking (Fmax  = 2.3 kN) to stumbling (Fmax  = 5.3 kN).
      Translational and rotational micromotions at the taper interface and seating
      characteristics during assembly and loading were determined using four eddy
      current sensors. Seating during loading after implant assembly was dependent on
      load magnitude but not on material coupling. Micromotions in the stem-neck
      interface correlated positively with load levels (CoCr: 2.6-6.3 um, Ti: 4.6-13.8
      um; p < 0.001) with Ti neck adapters exhibiting significantly larger micromotions
      than CoCr (p < 0.001). These findings explain why high body weights and
      activities related to higher loads could increase the risk of fretting-induced
      implant failures in clinical application, especially for Ti-Ti combinations.
      Still, the role of taper seating is not clearly understood.

PMID- 23553891
TI  - Blood oxygenation level dependent, blood volume, and blood flow responses to
      carbogen and hypoxic hypoxia in 9L rat gliomas as measured by MRI.
AB  - PURPOSE: To study vascular responsiveness to hypoxia and hypercarbia together
      with vessel size index (VSI) in a 9L rat glioma (n = 11) using multimodal MRI.
      MATERIALS AND METHODS: VSI was determined using T2 and T2* MRI following AMI-227
      contrast agent. Blood oxygenation level dependent (BOLD) signal response was
      determined using T2 EPI MRI, blood volume changes using AMI-227 and blood flow by
      means of continuous arterial spin labeling. RESULTS: VSI in the cortex, tumor
      rim, and core of 2.2 +/- 1.0, 18.2 +/- 5.4, and 23.9 +/- 14.7 MUm, respectively,
      showing a larger average vessel size in glioma than in the brain parenchyma. BOLD
      and blood volume signal changes to hypoxia and hypercapnia were much more
      profound in the tumor rim than the core. Hypoxia led to rim BOLD signal change
      that was larger in amplitude and it attained the low value much faster than
      either core or brain cortex. The vasculature in the rim appears more responsive
      to respiratory challenges in terms of volume adaptation than the core. Blood flow
      values within the gliomas were much lower than in the contralateral brain.
      Neither hypercarbia nor hypoxia had an effect on the tumor blood flow.
      CONCLUSION: Vascular responses of 9L gliomas to respiratory challenge, in
      particular hypoxia, are heterogeneous between the core and rim zones, potentially
      offering a means to classify and separate intratumor tissues with differing
      hemodynamic characteristics.

PMID- 23553897
TI  - Screening and production of a potent extracellular Arthrobacter creatinolyticus
      urease for determination of heavy metal ions.
AB  - This paper describes the isolation of a potent extracellular urease producing
      microorganism, identified by 16S rRNA as Arthrobacter creatinolyticus MTCC 5604
      and its medium optimization by classical one-factor-at-a-time method and central
      composite rotatable design (CCRD), a tool of response surface methodology (RSM).
      An optimal activity of 9.0 U ml(-1) was obtained by classical method and
      statistical optimization of the medium resulted in an activity of 17.35 U ml(-1)
      at 48 h and 30  degrees C. This activity was 4.91 times greater than the initial
      activity (3.53 U ml(-1) ) from the basal medium and the enzyme showed maximum
      activity at pH 8.0 and 60  degrees C and was stable at pH 7.0-9.0 and
      temperatures up to 50  degrees C. Furthermore, the enzyme was assessed for its
      activity reduction by determining the inhibitory concentration (IC50 ) of heavy
      metal ions and the inhibition of urease was in the order of Cu(II) > Cd(II) >
      Zn(II) > Ni(II). Urease was highly sensitive to Cu(II) and its inhibition was 94%
      and 100% in model solutions containing a mixture of Cu(II) with heavy metal ions
      Cd(II) and Zn(II), respectively. The results of these studies suggested that the
      enzyme could be utilized as sensors to determine the levels of Cu(II) ions in
      industrial effluents, contaminated soil and ground water. 

PMID- 23553895
TI  - Fiber type characterization in skeletal muscle by diffusion tensor imaging.
AB  - Fiber type distribution within a skeletal muscle, i.e. the quantification of the
      relative amount of type 1 (slow-twitching) and type 2 (fast-twitching) muscle
      fibers, is of great interest for the monitoring of the effects of training or the
      treatment of muscle diseases. The purpose of this study was to determine the
      feasibility of diffusion tensor imaging (DTI) as a tool for noninvasive fiber
      type quantification in human skeletal muscle. The right calves of 12 healthy
      volunteers were examined using DTI at 1.5 T. Standard DTI parameters, including
      fractional anisotropy (FA), and mean, radial and parallel diffusivity (MD, RD and
      PD, respectively), were determined in the soleus muscle. Fiber type proportion
      and mean fiber diameter within the soleus muscle were quantified from tissue
      specimens obtained via a fine needle biopsy. Linear regression analysis tested
      for associations between DTI and biopsy results. FA values were correlated
      significantly with fiber type proportion, such that higher FA values indicated a
      higher proportion of type 1 fibers (R(2)  = 0.5, p = 0.01). This was based on
      lower diffusivity perpendicular to the main axis of the fiber in subjects with a
      higher type 1 fiber proportion (RD: R(2)  = 0.52, p = 0.008). MD was also
      correlated with the proportion of type 1 fibers (R(2)  = 0.37, p = 0.037),
      whereas PD showed no significant correlation. DTI is a promising method for the
      noninvasive estimation of fiber type proportion in skeletal muscle. This
      technique may be used to monitor training effects or may be further developed as
      a biomarker in certain muscle diseases.

PMID- 23553898
TI  - Planning and evaluating clinical trials with composite time-to-first-event
      endpoints in a competing risk framework.
AB  - Composite endpoints combine several events of interest within a single variable.
      These are often time-to-first-event data, which are analyzed via survival
      analysis techniques. To demonstrate the significance of an overall clinical
      benefit, it is sufficient to assess the test problem formulated for the
      composite. However, the effect observed for the composite does not necessarily
      reflect the effects for the components. Therefore, it would be desirable that the
      sample size for clinical trials using composite endpoints provides enough power
      not only to detect a clinically relevant superiority for the composite but also
      to address the components in an adequate way. The single components of a
      composite endpoint assessed as time-to-first-event define competing risks. We
      consider multiple test problems based on the cause-specific hazards of competing
      events to address the problem of analyzing both a composite endpoint and its
      components. Thereby, we use sequentially rejective test procedures to reduce the
      power loss to a minimum. We show how to calculate the sample size for the given
      multiple test problem by using a simply applicable simulation tool in SAS. Our
      ideas are illustrated by two clinical study examples.

PMID- 23553899
TI  - Red blood cell distribution width is a predictor of readmission in cardiac
      patients.
AB  - BACKGROUND: Three-quarters of rehospitalizations ($44 billion yearly estimated
      cost) may be avoidable. A screening tool for the detection of potential
      readmission may facilitate more efficient case management. HYPOTHESIS: An
      elevated red blood cell distribution width (RDW) is an independent predictor of
      hospital readmission in patients with unstable angina (UA) or non-ST-elevation
      myocardial infarction (NSTEMI). METHODS: The study is a retrospective
      observational cohort analysis of adults admitted in 2007 with UA or NSTEMI. Data
      were gathered by review of inpatient medical records. The rate of 30-day
      nonelective readmission and time to nonelective readmission were recorded until
      November 1, 2011, and compared by RDW group using the 95th percentile (16.3%) as
      a cutoff. RESULTS: The median follow-up time of the 503 subjects (average age, 65
      +/- 13 years; 56% male) was 3.8 years (interquartile range: 0.3-4.3 years). Those
      readmitted within 30 days were older, had more comorbidities and higher RDW and
      creatinine levels, and were more likely to have had an intervention. At 3.8 years
      of follow-up, subjects with high RDW (>16.3%) were more likely to be readmitted
      compared to those with normal RDW (<=16.3%) (72.28% vs 59.95%, P = 0.003). In
      multivariable analyses, high RDW was a statistically significant predictor of
      readmission in general (hazard ratio: 1.35 (95% confidence interval [CI]:1.02
      1.79), P = 0.033) but not of 30-day rehospitalization (odds ratio: 1.34 (95% CI:
      0.78-2.31), P = 0.292). Its area under the receiver operating characteristic
      curve was 0.54 (sensitivity 23% and specificity 85%). CONCLUSIONS: An elevated
      RDW is an independent predictor of hospital readmission in patients with UA or
      NSTEMI.

PMID- 23553900
TI  - Low myo-inositol indicating astrocytic damage in a case series of neuromyelitis
      optica.
AB  - Astrocytic necrosis is a prominent pathological feature of neuromyelitis optica
      (NMO) lesions and is clinically relevant. We report 5 NMO-related cases, all with
      longitudinally extensive lesions in the upper cervical cord, who underwent
      cervical cord (1) H-magnetic resonance spectroscopy. Lower myo-inositol/creatine
      values, suggesting astrocytic damage, were consistently found within the NMO
      lesions when compared with healthy controls and patients with multiple sclerosis
      (MS), who showed at least 1 demyelinating lesion at the same cord level.
      Therefore, the in vivo quantification of myo-inositol may distinguish NMO from
      MS. This is an important step toward developing imaging markers for clinical
      trials in NMO.

PMID- 23553901
TI  - Efficacy comparison of traditional Chinese medicine LQ versus gemcitabine in a
      mouse model of pancreatic cancer.
AB  - Pancreatic cancer is highly treatment-resistant and has one of the highest
      fatality rates of all cancers and is the fourth highest cancer killer worldwide.
      Novel, more effective strategies are needed to treat this disease. We report here
      on the use of patient-like orthotopic nude-mouse models of human metastatic
      pancreatic cancer to compare the traditional Chinese medicine (TCM) herbal
      mixture LQ to gemcitabine, which is first-line therapy for this disease, for anti
      metastatic and anti-tumor activity as well as safety. The human pancreatic cancer
      cell line, MiaPaCa-2, labeled with red fluorescent protein (RFP), was used for
      the orthotopic model. LQ (gavage, 600 mg/kg/day) significantly inhibited
      pancreatic cancer tumor growth and metastasis, as measured by imaging, with no
      overt toxicity. Survival of tumor-bearing mice was also prolonged by LQ. The
      therapeutic efficacy of LQ is comparable with gemcitabine but with less toxicity,
      as indicated by a lack of body-weight loss with LQ, but not gemcitabine. The
      results indicate that TCM can have non-toxic efficacy against metastatic
      pancreatic cancer comparable to gemcitabine in a clinically-relevant orthotopic
      mouse model.

PMID- 23553903
TI  - Crystal-facet engineering of ferric giniite by using ionic-liquid precursors and
      their enhanced photocatalytic performances under visible-light irradiation.
AB  - In the work presented here, well-dispersed ferric giniite microcrystals with
      controlled sizes and shapes are solvothermally synthesized from ionic-liquid
      precursors by using 1-n-butyl-3-methylimidazolium dihydrogenphosphate
      ([Bmim][H2PO4]) as phosphate source. The success of this synthesis relies on the
      concentration and composition of the ionic-liquid precursors. By adjusting the
      molar ratios of Fe(NO3)3.9H2O to [Bmim][H2PO4] as well as the composition of
      ionic-liquid precursors, we obtained uniform microstructures such as bipyramids
      exposing {111} facets, plates exposing {001} facets, hollow spheres, tetragonal
      hexadecahedron exposing {441} and {111} facets, and truncated bipyamids with
      carved {001} facets. The crystalline structure of the ferric giniite
      microcrystals is disclosed by various characterization techniques. It was
      revealed that [Bmim][H2PO4] played an important role in stabilizing the {111}
      facets of ferric giniite crystals, leading to the different morphologies in the
      presence of ionic-liquid precursors with different compositions. Furthermore,
      since these ferric giniite crystals were characterized by different facets, they
      could serve as model Fenton-like catalysts to uncover the correlation between the
      surface and the catalytic performance for the photodegradation of organic dyes
      under visible-light irradiation. Our measurements indicate that the
      photocatalytic activity of as-prepared Fenton-like catalysts is highly dependent
      on the exposed facets, and the surface area has essentially no obvious effect on
      the photocatalytic degradation of organic dyes in the present study. It is highly
      expected that these findings are useful in understanding the photocatalytic
      activity of Fenton-like catalysts with different morphologies, and suggest a
      promising new strategy for crystal-facet engineering of photocatalysts for
      wastewater treatment based on heterogeneous Fenton-like process.

PMID- 23553902
TI  - Brief report: CD24 and CD44 mark human intestinal epithelial cell populations
      with characteristics of active and facultative stem cells.
AB  - Recent seminal studies have rapidly advanced the understanding of intestinal
      epithelial stem cell (IESC) biology in murine models. However, the lack of
      techniques suitable for isolation and subsequent downstream analysis of IESCs
      from human tissue has hindered the application of these findings toward the
      development of novel diagnostics and therapies with direct clinical relevance.
      This study demonstrates that the cluster of differentiation genes CD24 and CD44
      are differentially expressed across LGR5 positive "active" stem cells as well as
      HOPX positive "facultative" stem cells. Fluorescence-activated cell sorting
      enables differential enrichment of LGR5 (CD24-/CD44+) and HOPX (CD24+/CD44+)
      cells for gene expression analysis and culture. These findings provide the
      fundamental methodology and basic cell surface signature necessary for isolating
      and studying intestinal stem cell populations in human physiology and disease.

PMID- 23553904
TI  - Estimating economic thresholds for site-specific weed control using manual weed
      counts and sensor technology: an example based on three winter wheat trials.
AB  - BACKGROUND: Precision experimental design uses the natural heterogeneity of
      agricultural fields and combines sensor technology with linear mixed models to
      estimate the effect of weeds, soil properties and herbicide on yield. These
      estimates can be used to derive economic thresholds. Three field trials are
      presented using the precision experimental design in winter wheat. Weed densities
      were determined by manual sampling and bi-spectral cameras, yield and soil
      properties were mapped. RESULTS: Galium aparine, other broad-leaved weeds and
      Alopecurus myosuroides reduced yield by 17.5, 1.2 and 12.4 kg ha(-1) plant(-1) 
      m(2) in one trial. The determined thresholds for site-specific weed control with
      independently applied herbicides were 4, 48 and 12 plants m(-2), respectively.
      Spring drought reduced yield effects of weeds considerably in one trial, since
      water became yield limiting. A negative herbicide effect on the crop was
      negligible, except in one trial, in which the herbicide mixture tended to reduce
      yield by 0.6 t ha(-1). Bi-spectral cameras for weed counting were of limited use
      and still need improvement. Nevertheless, large weed patches were correctly
      identified. CONCLUSION: The current paper presents a new approach to conducting
      field trials and deriving decision rules for weed control in farmers' fields.

PMID- 23553905
TI  - An analysis of skeletal development in osteoblast-specific and chondrocyte
      specific runt-related transcription factor-2 (Runx2) knockout mice.
AB  - Global gene deletion studies in mice and humans have established the pivotal role
      of runt related transcription factor-2 (Runx2) in both intramembranous and
      endochondral ossification processes during skeletogenesis. In this study, we for
      the first time generated mice carrying a conditional Runx2 allele with exon 4,
      which encodes the Runt domain, flanked by loxP sites. These mice were crossed
      with alpha1(I)-collagen-Cre or alpha1(II)-collagen-Cre transgenic mice to obtain
      osteoblast-specific or chondrocyte-specific Runx2 deficient mice, respectively.
      As seen in Runx2(-/-) mice, perinatal lethality was observed in alpha1(II)
      Cre;Runx2(flox/flox) mice, but this was not the case in animals in which
      alpha1(I)-collagen-Cre was used to delete Runx2. When using double-staining with
      Alizarin red for mineralized matrix and Alcian blue for cartilaginous matrix, we
      observed previously that mineralization was totally absent at embryonic day 15.5
      (E15.5) throughout the body in Runx2(-/-) mice, but was found in areas undergoing
      intramembranous ossification such as skull and clavicles in alpha1(II)
      Cre;Runx2(flox/flox) mice. In newborn alpha1(II)-Cre;Runx2(flox/flox) mice,
      mineralization impairment was restricted to skeletal areas undergoing
      endochondral ossification including long bones and vertebrae. In contrast, no
      apparent skeletal abnormalities were seen in mutant embryo, newborn, and 3-week
      old to 6-week old-mice in which Runx2 had been deleted with the alpha1(I)
      collagen-Cre driver. These results suggest that Runx2 is absolutely required for
      endochondral ossification during embryonic and postnatal skeletogenesis, but that
      disrupting its expression in already committed osteoblasts as achieved here with
      the alpha1(I)-collagen-Cre driver does not affect overtly intramembranous and
      endochondral ossification. The Runx2 floxed allele established here is
      undoubtedly useful for investigating the role of Runx2 in particular cells.

PMID- 23553906
TI  - Intramolecular pnicogen interactions in PHF-(CH2)(n)-PHF (n=2-6) systems.
AB  - A computational study of the intramolecular pnicogen bond in PHF-(CH2)n-PHF (n=2
      6) systems was carried out. For each compound, two different conformations, (R,R)
      and (R,S), were considered on the basis of the chirality of the phosphine groups.
      The characteristics of the closed conformers, in which the pnicogen interaction
      occurs, were compared with those of the extended conformer. In several cases, the
      closed conformations are more stable than the extended conformations. The
      calculated interaction energies of the pnicogen contact, by means of isodesmic
      reactions, provide values between -3.4 and -26.0 kJ mol(-1). Atoms in molecules
      and electron localization function analysis of the electron density showed that
      the systems in the closed conformations with short P...P distances have a partial
      covalent character in this interaction. The calculated absolute chemical
      shieldings of the P atoms showed an exponential relationship with the P...P
      distance. In addition, a search in the Cambridge crystallographic database was
      carried out to detect those compounds with a potential intramolecular pnicogen
      bond in the solid phase.

PMID- 23553907
TI  - A novel pixellated solid-state photon detector for enhancing the Everhart
      Thornley detector.
AB  - This article presents a pixellated solid-state photon detector designed
      specifically to improve certain aspects of the existing Everhart-Thornley
      detector. The photon detector was constructed and fabricated in an
      Austriamicrosystems 0.35 um complementary metal-oxide-semiconductor process
      technology. This integrated circuit consists of an array of high-responsivity
      photodiodes coupled to corresponding low-noise transimpedance amplifiers, a
      selector-combiner circuit and a variable-gain postamplifier. Simulated and
      experimental results show that the photon detector can achieve a maximum
      transimpedance gain of 170 dBOmega and minimum bandwidth of 3.6 MHz. It is able
      to detect signals with optical power as low as 10 nW and produces a minimum
      signal-to-noise ratio (SNR) of 24 dB regardless of gain configuration. The
      detector has been proven to be able to effectively select and combine signals
      from different pixels. The key advantages of this detector are smaller
      dimensions, higher cost effectiveness, lower voltage and power requirements and
      better integration. The photon detector supports pixel-selection configurability
      which may improve overall SNR and also potentially generate images for different
      analyses. This work has contributed to the future research of system-level
      integration of a pixellated solid-state detector for secondary electron detection
      in the scanning electron microscope.

PMID- 23553908
TI  - Enticing cobalt into planarity: can a pair of diolato ligands make it happen?

PMID- 23553909
TI  - On the role of intrinsic and extrinsic forces in early cardiac S-looping.
AB  - BACKGROUND: Looping is a crucial phase during heart development when the
      initially straight heart tube is transformed into a shape that more closely
      resembles the mature heart. Although the genetic and biochemical pathways of
      cardiac looping have been well studied, the biophysical mechanisms that actually
      effect the looping process remain poorly understood. Using a combined
      experimental (chick embryo) and computational (finite element modeling) approach,
      we study the forces driving early s-looping when the primitive ventricle moves to
      its definitive position inferior to the common atrium. RESULTS: New results from
      our study indicate that the primitive heart has no intrinsic ability to form an s
      loop and that extrinsic forces are necessary to effect early s-looping. They
      support previous studies that established an important role for cervical flexure
      in causing early cardiac s-looping. Our results also show that forces applied by
      the splanchnopleure cannot be ignored during early s-looping and shed light on
      the role of cardiac jelly. Using available experimental data and computer
      modeling, we successfully developed and tested a hypothesis for the force
      mechanisms driving s-loop formation. CONCLUSIONS: Forces external to the
      primitive heart tube are necessary in the later stages of cardiac looping.
      Experimental and model results support our proposed hypothesis for forces driving
      early s-looping.

PMID- 23553910
TI  - Software-assisted small bowel motility analysis using free-breathing MRI:
      feasibility study.
AB  - PURPOSE: To validate a software prototype allowing for small bowel motility
      analysis in free breathing by comparing it to manual measurements. MATERIALS AND
      METHODS: In all, 25 patients (15 male, 10 female; mean age 39 years) were
      included in this Institutional Review Board-approved, retrospective study.
      Magnetic resonance imaging (MRI) was performed on a 1.5T system after
      standardized preparation acquiring motility sequences in free breathing over 69
      84 seconds. Small bowel motility was analyzed manually and with the software.
      Functional parameters, measurement time, and reproducibility were compared using
      the coefficient of variance and paired Student's t-test. Correlation was analyzed
      using Pearson's correlation coefficient and linear regression. RESULTS: The 25
      segments were analyzed twice both by hand and using the software with automatic
      breathing correction. All assessed parameters significantly correlated between
      the methods (P < 0.01), but the scattering of repeated measurements was
      significantly (P < 0.01) lower using the software (3.90%, standard deviation [SD]
      +/- 5.69) than manual examinations (9.77%, SD +/- 11.08). The time needed was
      significantly less (P < 0.001) with the software (4.52 minutes, SD +/- 1.58)
      compared to manual measurement, lasting 17.48 minutes for manual (SD +/- 1.75
      minutes). CONCLUSION: The use of the software proves reliable and faster small
      bowel motility measurements in free-breathing MRI compared to manual analyses.
      The new technique allows for analyses of prolonged sequences acquired in free
      breathing, improving the informative value of the examinations by amplifying the
      evaluable data.

PMID- 23553911
TI  - Electron accepting porphycenes on graphene.
AB  - The versatility of nanographene (NG) as an electron donor is demonstrated when
      integrated together with an electron accepting porphycene into a novel electron
      NG hybrid. This feature is further exploited in dye-sensitized solar cells
      (DSSCs), in which photoanodes (ZnO) reveal a cascade of electron flow as modus
      operandi.

PMID- 23553912
TI  - A calibration-based approach to real-time in vivo monitoring of pyruvate C1 and
      C2 polarization using the JCC spectral asymmetry.
AB  - A calibration-based technique for real-time measurement of pyruvate polarization
      by partial integral analysis of the doublet from the neighbouring J-coupled
      carbon is presented. In vitro calibration data relating the C2 and C1 asymmetries
      to the instantaneous C1 and C2 polarizations, respectively, were acquired in
      blood. The feasibility of using the in vitro calibration data to determine the
      instantaneous in vivo C1 and C2 polarizations was demonstrated in the analysis of
      rat kidney and pig heart spectral data. An approach for incorporating this
      technique into in vivo protocols is proposed.

PMID- 23553913
TI  - Elevated rho-kinase activity as a marker indicating atherosclerosis and
      inflammation burden in polyvascular disease patients with concomitant coronary
      and peripheral arterial disease.
AB  - BACKGROUND: Recent evidence suggests that Rho-kinase (ROCK) plays an important
      role in the pathogenesis of atherosclerosis and a marker of atherosclerotic
      burden. Polyvascular disease with concomitant peripheral arterial disease (PAD)
      and coronary artery disease (CAD) is common and associated with a worse
      prognosis. The aim of this study was to evaluate ROCK activity as a marker of
      polyvascular disease. HYPOTHESIS:  METHODS: We retrospectively analyzed patients
      undergoing coronary angiography at our institution between February 2009 and May
      2009. Patients with only CAD (n = 40) defined by coronary artery stenosis of
      >=50% by angiography, only PAD (n = 40) defined by an ankle brachial index (ABI)
      <0.9, and combined CAD/PAD (n = 40) were matched by age and sex to control
      patients (n = 40) without CAD or PAD. ROCK activity was determined by
      phosphorylation of the myosin binding subunit in leukocytes and then compared
      between each group. Multivariate analysis was used to determine independent
      predictors of polyvascular disease. Discriminative ability of elevated ROCK
      activity was assessed using receiver operator characteristics (ROC) curves.
      RESULTS: Patients (age 68 +/- 12 years, 79% male) with CAD, PAD, and CAD/PAD had
      a mean ABI of 1.08, 0.62, and 0.65, respectively, compared to 1.08 in the control
      group. There was an incremental increase in ROCK activity in patients with CAD
      (4.61 +/- 2.11), PAD (4.27 +/- 1.39), and CAD/PAD (5.96 +/- 1.94) compared to
      control (2.40 +/- 0.43) (all P < 0.05). ROCK activity (odds ratio: 4.53, 95%
      confidence interval: 1.26-6.30) was an independent predictor of polyvascular
      disease. The ROCK cutoff value of 4.85 had a sensitivity of 72.7% and a
      specificity of 65.7%, with an area under ROC curve of 0.71 for polyvascular
      disease. CONCLUSIONS: Patients with concomitant peripheral and coronary arterial
      disease are associated with increased Rho-kinase activity. Rho-kinase activity
      may be a potential marker of atherosclerotic burden for patients with
      polyvascular disease.

PMID- 23553914
TI  - Bayesian semiparametric mixture Tobit models with left censoring, skewness, and
      covariate measurement errors.
AB  - Common problems to many longitudinal HIV/AIDS, cancer, vaccine, and environmental
      exposure studies are the presence of a lower limit of quantification of an
      outcome with skewness and time-varying covariates with measurement errors. There
      has been relatively little work published simultaneously dealing with these
      features of longitudinal data. In particular, left-censored data falling below a
      limit of detection may sometimes have a proportion larger than expected under a
      usually assumed log-normal distribution. In such cases, alternative models, which
      can account for a high proportion of censored data, should be considered. In this
      article, we present an extension of the Tobit model that incorporates a mixture
      of true undetectable observations and those values from a skew-normal
      distribution for an outcome with possible left censoring and skewness, and
      covariates with substantial measurement error. To quantify the covariate process,
      we offer a flexible nonparametric mixed-effects model within the Tobit framework.
      A Bayesian modeling approach is used to assess the simultaneous impact of left
      censoring, skewness, and measurement error in covariates on inference. The
      proposed methods are illustrated using real data from an AIDS clinical study. .

PMID- 23553915
TI  - Microsomal prostaglandin E synthase-1 is induced in alzheimer's disease and its
      deletion mitigates alzheimer's disease-like pathology in a mouse model.
AB  - Epidemiological studies have suggested that long-term use of nonsteroidal anti
      inflammatory drugs that inhibit cyclooxygenase (COX) activity can moderate the
      onset or progression of Alzheimer's disease (AD). Thus it has been suggested that
      prostaglandin E2 (PGE2 ), a major end-product of COX, may play a pathogenic role
      in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream
      from COX, has not been fully elucidated. Here we found that, among three PGES
      enzymes, only microsomal PGES-1 (mPGES-1) is induced, and its expression is
      associated with beta-amyloid (Abeta) plaques in the cerebral cortex in human AD
      patients and in Tg2576 mice, a transgenic AD mouse model. Furthermore, to
      investigate whether mPGES-1 contributes to AD-like pathology, we bred mPGES-1
      deficient mice with Tg2576 mice. We found that mPGES-1 deletion reduced the
      accumulation of microglia around senile plaques and attenuated learning
      impairments in Tg2576 mice. These results indicated that mPGES-1 is induced in
      the AD brain and thus plays a role in AD pathology. Blockage of mPGES-1 could
      form the basis for a novel therapeutic strategy for patients with AD.

PMID- 23553916
TI  - The temporal response to drought in a Mediterranean evergreen tree: comparing a
      regional precipitation gradient and a throughfall exclusion experiment.
AB  - Like many midlatitude ecosystems, Mediterranean forests will suffer longer and
      more intense droughts with the ongoing climate change. The responses to drought
      in long-lived trees differ depending on the time scale considered, and short-term
      responses are currently better understood than longer term acclimation. We
      assessed the temporal changes in trees facing a chronic reduction in water
      availability by comparing leaf-scale physiological traits, branch-scale hydraulic
      traits, and stand-scale biomass partitioning in the evergreen Quercus ilex across
      a regional precipitation gradient (long-term changes) and in a partial
      throughfall exclusion experiment (TEE, medium term changes). At the leaf scale,
      gas exchange, mass per unit area and nitrogen concentration showed homeostatic
      responses to drought as they did not change among the sites of the precipitation
      gradient or in the experimental treatments of the TEE. A similar homeostatic
      response was observed for the xylem vulnerability to cavitation at the branch
      scale. In contrast, the ratio of leaf area over sapwood area (LA/SA) in young
      branches exhibited a transient response to drought because it decreased in
      response to the TEE the first 4 years of treatment, but did not change among the
      sites of the gradient. At the stand scale, leaf area index (LAI) decreased, and
      the ratios of stem SA to LAI and of fine root area to LAI both increased in trees
      subjected to throughfall exclusion and from the wettest to the driest site of the
      gradient. Taken together, these results suggest that acclimation to chronic
      drought in long-lived Q. ilex is mediated by changes in hydraulic allometry that
      shift progressively from low (branch) to high (stand) organizational levels, and
      act to maintain the leaf water potential within the range of xylem hydraulic
      function and leaf photosynthetic assimilation. 

PMID- 23553917
TI  - Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the
      pediatric preclinical testing program.
AB  - BACKGROUND: Antimitotic agents are essential components for curative therapy of
      pediatric acute leukemias and many solid tumors. Eribulin is a novel agent that
      differs from both Vinca alkaloids and taxanes in its mode of binding to tubulin
      polymers. PROCEDURES: Eribulin was tested against the PPTP in vitro cell line
      panel at concentrations from 0.1 nM to 1.0 MUM and against the PPTP in vivo
      xenograft panels at a dose of 1 mg/kg (solid tumors) or 1.5 mg/kg (ALL models)
      using a q4dx3 schedule repeated at Day 21. RESULTS: In vitro eribulin
      demonstrated cytotoxic activity, with a median relative IC50 value of 0.27 nM,
      (range <0.1-14.8 nM). Eribulin was well tolerated in vivo, and all 43 xenograft
      models were considered evaluable for efficacy. Eribulin induced significant
      differences in event-free survival (EFS) distribution compared to control in 29
      of 35 (83%) of the solid tumors and in 8 of 8 (100%) of the ALL xenografts.
      Objective responses were observed in 18 of 35 (51%) solid tumor xenografts.
      Complete responses (CR) or maintained CR were observed in panels of Wilms tumor,
      Ewing sarcoma, rhabdomyosarcoma, glioblastoma, and osteosarcoma xenografts. All
      eight ALL xenografts achieved CR or MCR. CONCLUSIONS: The high level of activity
      observed for eribulin against the PPTP preclinical models makes this an
      interesting agent to consider for pediatric evaluation. The activity pattern
      observed for eribulin in the solid tumor panels is equal or superior to that
      observed previously for vincristine.

PMID- 23553919
TI  - "Head-to-toe" kissing balloon angioplasty during PCI of right coronary artery
      chronic total occlusion.
AB  - New techniques involving the use of retrograde channels have enabled successful
      revascularization of chronically occluded arteries previously not amenable to
      standard strategies. We describe the use of a simultaneous antegrade and
      retrograde approach to perform bifurcation kissing balloon angioplasty which was
      not possible using a standard antegrade approach. As the balloons are oriented in
      opposite rather than identical directions, we have named this technique "Head-to
      Toe Kissing."

PMID- 23553920
TI  - Synthesis, tautomeric structures, and antitumor activity of new perimidines.
AB  - New series of perimidine derivatives and fused perimidines were derived from the
      reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl
      chlorides. In addition, 8,10-disubstituted-[1,2,4]triazolo[4,3-a]perimidines (20a
      m) were prepared through the reaction of perimidine-2-thione (15) with
      hydrazonoyl chlorides. The structures of the newly synthesized compounds were
      established on the basis of spectral data and elemental analyses. Some products
      were investigated for their antitumor activities against the human breast cancer
      cell line MCF-7 and the liver carcinoma cell line HEPG-2, and the results of some
      derivatives showed promising activity.

PMID- 23553918
TI  - Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate
      cardiac hypertrophy and attenuate autophagy during exercise.
AB  - The carboxyl terminus of Hsp70-interacting protein (CHIP) is a ubiquitin
      ligase/cochaperone critical for the maintenance of cardiac function. Mice lacking
      CHIP (CHIP-/-) suffer decreased survival, enhanced myocardial injury and
      increased arrhythmias compared with wild-type controls following challenge with
      cardiac ischaemia reperfusion injury. Recent evidence implicates a role for CHIP
      in chaperone-assisted selective autophagy, a process that is associated with
      exercise-induced cardioprotection. To determine whether CHIP is involved in
      cardiac autophagy, we challenged CHIP-/- mice with voluntary exercise. CHIP-/-
      mice respond to exercise with an enhanced autophagic response that is associated
      with an exaggerated cardiac hypertrophy phenotype. No impairment of function was
      identified in the CHIP-/- mice by serial echocardiography over the 5 weeks of
      running, indicating that the cardiac hypertrophy was physiologic not pathologic
      in nature. It was further determined that CHIP plays a role in inhibiting Akt
      signalling and autophagy determined by autophagic flux in cardiomyocytes and in
      the intact heart. Taken together, cardiac CHIP appears to play a role in
      regulating autophagy during the development of cardiac hypertrophy, possibly by
      its role in supporting Akt signalling, induced by voluntary running in vivo.

PMID- 23553921
TI  - Incorporating into a Calpha Go model the effects of geometrical restriction on
      Calpha atoms caused by side chain orientations.
AB  - Coarse-grained Go models have been widely used for studying protein-folding
      mechanisms. Despite the simplicity of the model, these can reproduce the
      essential features of the folding process of a protein. However, it is also known
      that side chains significantly contribute to the folding mechanism. Hence, it is
      desirable to incorporate the side chain effects into a coarse-grained Go model.
      In this study, to distinguish the effects of side chain orientation and to
      understand how these effects contribute to folding mechanisms, we incorporate
      into a Calpha Go model not only heterogeneous contact energies but also
      geometrical restraints around two Calpha atoms in contact with each other. We
      confirm that the heterogeneity of contact energies governs the folding pathway of
      a protein and that the geometric constraints attributed to side chains reproduce
      cooperative transitions in folding.

PMID- 23553922
TI  - Synthesis of biotinylated aldehyde polymers for biomolecule conjugation.
AB  - Biotinylated polymers with side-chain aldehydes were prepared for use as
      multifunctional scaffolds. Two different biotin-containing chain transfer agents
      (CTAs) and an aldehyde-containing monomer, 6-oxohexyl acrylate (6OHA), are
      synthesized. Poly(ethylene glycol) methyl ether acrylate (PEGA) and 6OHA are
      copolymerized by reversible addition-fragmentation chain transfer (RAFT)
      polymerization in the presence of the biotinylated CTAs. The resulting polymers
      are analyzed by GPC and(1) H NMR spectroscopy. The polymer end groups contained a
      disulfide bond, which could be readily reduced in solution to remove the biotin.
      Reactivity of the aldehyde side chains is demonstrated by oxime and hydrazone
      formation at the polymer side chains, and conjugate formation of fluorescently
      labeled polymers with streptavidin is investigated by gel electrophoresis.

PMID- 23553923
TI  - Fitness of twospotted spider mites is more affected by constitutive than induced
      resistance traits in cotton (Gossypium spp.).
AB  - BACKGROUND: Life history parameters are useful tools for comparing the fitness of
      pests on different host plants. This study compared life history parameters of
      twospotted spider mites (Tetranychus urticae Koch) on two resistant cotton
      Gossypium genotypes (BM13H and Sipima 280) and one susceptible genotype (Sicot
      71). The effects of both constitutive and induced defences were assessed.
      RESULTS: Mites reared on the resistant genotypes had longer immature development
      times, lower immature survival and reduced adult fecundity. Mites reared on BM13H
      that had been induced by prior exposure to mites had a small additional decrease
      in adult fecundity. The contribution to mite resistance of constitutive
      resistance mechanisms was much greater than induced responses. The effect of
      morphological constitutive defences was minor, implicating biochemical defences
      as the major mite-resistance mechanism. Sensitivity analysis and a population
      development study using life history parameters of mites showed that a lower
      immature survival rate on resistant genotypes had the greatest effect on mite
      fitness and population development. CONCLUSION: Use of life history parameters
      provided valuable insight into the mite-resistance mechanisms of these Gossypium
      genotypes. Further, the results largely explained mite population development on
      these genotypes in the field.

PMID- 23553924
TI  - Petrus Camper: A history and overview of the clinical importance of Camper's
      fascia in surgical anatomy.
AB  - Petrus Camper's contributions to modern anatomical science include descriptions
      of the foot, upper limb, axilla, and inguinal region. His explanation of the
      etiology of inguinal hernias revolutionized the surgical practice of their
      repair. Camper's description of abdominal anatomy was an invaluable contribution
      to the field of abdominal surgery. Current research reviewed in this article
      shows the importance of understanding the layers of the abdominal wall, notably
      Camper's fascia, the closure of which has been found to be vital to proper wound
      healing and patient recovery. This article begins with a biography of Petrus
      Camper and his research in the inguinal region. It continues with anatomical and
      histological descriptions of Camper's fascia and finishes with its clinical
      correlates in surgical practice.

PMID- 23553925
TI  - Needle puncture injury causes acute and long-term mechanical deficiency in a
      mouse model of intervertebral disc degeneration.
AB  - Low back pain is a significant socioeconomic burden and intervertebral disc
      degeneration has been implicated as a cause. A reliable animal model of disc
      degeneration is necessary to evaluate therapeutics, and functional metrics are
      essential to quantify their benefit. To this end, needle puncture injuries were
      created in the caudal intervertebral discs of mice to induce disc degeneration.
      Compression, torsion, and creep mechanics were assessed both immediately and
      after eight weeks to distinguish between the effects of injury and the subsequent
      reparative or degenerative response. Two needle sizes (29 and 26 gauge) were used
      to determine injury size-dependence. Compressive stiffness (62%), torsional
      stiffness (60%), and early damping stiffness (84%) decreased immediately after
      injury with the large needle (26G). These mechanical properties did not change
      over time despite structural and compositional changes. At 8 weeks following
      large needle injury, disc height decreased (37%), nucleus pulposus (NP)
      glycosaminoglycan content decreased (41%), and NP collagen content increased
      (45%). The small needle size had no significant effect on mechanics and did not
      initiate degenerative changes in structure and composition. Thus, the injection
      of therapeutics into the NP with a minimal needle size may limit damage due to
      the needle insertion. These findings, along with the wide commercial availability
      of mouse-specific biological probes, indicate that the mouse caudal disc model
      can be a powerful tool for investigating disc degeneration and therapy.

PMID- 23553926
TI  - Re: "the influence of RAMP1 overexpression on CGRP-induced osteogenic
      differentiation in MG-63 cells in vitro: an experimental study".

PMID- 23553927
TI  - Generation of CF3-containing epoxides and aziridines by visible-light-driven
      trifluoromethylation of allylic alcohols and amines.
AB  - Radical reactions! Efficient methods for the generation of CF3-containing
      epoxides and aziridines have been developed (see scheme). A variety of allylic
      alcohols and allylic amines were transformed into the corresponding epoxides and
      aziridines by using [Ru(bpy)3]Cl2 (bpy = 2,2'-bipyridine), CF3 I, and 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) (or N,N,N',N'-tetramethylethylenediamine,
      TMEDA) under visible-light irradiation.

PMID- 23553929
TI  - Initial nitrous oxide, carbon dioxide, and methane costs of converting
      conservation reserve program grassland to row crops under no-till vs.
      conventional tillage.
AB  - Around 4.4 million ha of land in USDA Conservation Reserve Program (CRP)
      contracts will expire between 2013 and 2018 and some will likely return to crop
      production. No-till (NT) management offers the potential to reduce the global
      warming costs of CO2 , CH4 , and N2 O emissions during CRP conversion, but to
      date there have been no CRP conversion tillage comparisons. In 2009, we converted
      portions of three 9-21 ha CRP fields in Michigan to conventional tillage (CT) or
      NT soybean production and reserved a fourth field for reference. Both CO2 and N2
      O fluxes increased following herbicide application in all converted fields, but
      in the CT treatment substantial and immediate N2 O and CO2 fluxes occurred after
      tillage. For the initial 201-day conversion period, average daily N2 O fluxes (g
      N2 O-N ha(-1)  d(-1) ) were significantly different in the order: CT (47.5 +/-
      6.31, n = 6) ? NT (16.7 +/- 2.45, n = 6) ? reference (2.51 +/- 0.73, n = 4).
      Similarly, soil CO2 fluxes in CT were 1.2 times those in NT and 3.1 times those
      in the unconverted CRP reference field. All treatments were minor sinks for CH4 (
      0.69 +/- 0.42 to -1.86 +/- 0.37 g CH4 -C ha(-1)  d(-1) ) with no significant
      differences among treatments. The positive global warming impact (GWI) of
      converted soybean fields under both CT (11.5 Mg CO2 e ha(-1) ) and NT (2.87 Mg
      CO2 e ha(-1) ) was in contrast to the negative GWI of the unconverted reference
      field (-3.5 Mg CO2 e ha(-1) ) with on-going greenhouse gas (GHG) mitigation. N2 O
      contributed 39.3% and 55.0% of the GWI under CT and NT systems with the remainder
      contributed by CO2 (60.7% and 45.0%, respectively). Including foregone
      mitigation, we conclude that NT management can reduce GHG costs by ~60% compared
      to CT during initial CRP conversion. 

PMID- 23553928
TI  - An RNA-seq protocol to identify mRNA expression changes in mouse diaphyseal bone:
      applications in mice with bone property altering Lrp5 mutations.
AB  - Loss-of-function and certain missense mutations in the Wnt coreceptor low-density
      lipoprotein receptor-related protein 5 (LRP5) significantly decrease or increase
      bone mass, respectively. These human skeletal phenotypes have been recapitulated
      in mice harboring Lrp5 knockout and knock-in mutations. We hypothesized that
      measuring mRNA expression in diaphyseal bone from mice with Lrp5 wild-type
      (Lrp5(+/+) ), knockout (Lrp5(-/-) ), and high bone mass (HBM)-causing
      (Lrp5(p.A214V/+) ) knock-in alleles could identify genes and pathways that
      regulate or are regulated by LRP5 activity. We performed RNA-seq on pairs of
      tibial diaphyseal bones from four 16-week-old mice with each of the
      aforementioned genotypes. We then evaluated different methods for controlling for
      contaminating nonskeletal tissue (ie, blood, bone marrow, and skeletal muscle) in
      our data. These methods included predigestion of diaphyseal bone with collagenase
      and separate transcriptional profiling of blood, skeletal muscle, and bone
      marrow. We found that collagenase digestion reduced contamination, but also
      altered gene expression in the remaining cells. In contrast, in silico filtering
      of the diaphyseal bone RNA-seq data for highly expressed blood, skeletal muscle,
      and bone marrow transcripts significantly increased the correlation between RNA
      seq data from an animal's right and left tibias and from animals with the same
      Lrp5 genotype. We conclude that reliable and reproducible RNA-seq data can be
      obtained from mouse diaphyseal bone and that lack of LRP5 has a more pronounced
      effect on gene expression than the HBM-causing LRP5 missense mutation. We
      identified 84 differentially expressed protein-coding transcripts between LRP5
      "sufficient" (ie, Lrp5(+/+) and Lrp5(p.A214V/+) ) and "insufficient" (Lrp5(-/-) )
      diaphyseal bone, and far fewer differentially expressed genes between
      Lrp5(p.A214V/+) and Lrp5(+/+) diaphyseal bone.

PMID- 23553930
TI  - Essential role of Sox2 for the establishment and maintenance of the germ cell
      line.
AB  - Sox2 is a pluripotency-conferring gene expressed in primordial germ cells (PGCs)
      and postnatal oocytes, but the role it plays during germ cell development and
      early embryogenesis is unknown. Since Sox2 ablation causes early embryonic
      lethality shortly after blastocyst implantation, we generated mice bearing Sox2
      conditional deletion in germ cells at different stages of their development
      through the Cre/loxP recombination system. Embryos lacking Sox2 in PGCs show a
      dramatic decrease of germ cell numbers at the time of their specification. At
      later stages, we found that Sox2 is strictly required for PGC proliferation. On
      the contrary, Sox2 deletion in meiotic oocytes does not impair postnatal
      oogenesis and early embryogenesis, indicating that it is not essential for oocyte
      maturation or for zygotic development. We also show that Sox2 regulates Kit
      expression in PGCs and binds to discrete transcriptional regulatory sequences of
      this gene, which is known to be important for PGCs survival and proliferation.
      Sox2 also stimulates the expression of Zfp148, which is required for normal
      development of fetal germ cells, and Rif1, a potential regulator of PGC
      pluripotency.

PMID- 23553933
TI  - Reply: To PMID 23124930.

PMID- 23553932
TI  - Mapping glutamate in subcortical brain structures using high-resolution GluCEST
      MRI.
AB  - In vivo measurement of glutamate (Glu) in brain subcortex can elucidate the role
      these structures play in cognition and neuropsychiatric disorders. However,
      accurate quantification of Glu in subcortical regions is challenging. Recently, a
      novel MRI method based on the Glu chemical exchange saturation transfer (GluCEST)
      effect has been developed for detecting brain Glu in millimolar concentrations.
      Here, we use GluCEST to map Glu distributions in subcortical structures of the
      human brain (e.g. amygdala, hippocampus). Overall, GluCEST was ~40% higher in
      gray matter than in white matter. Within the subcortical gray matters, amygdala
      showed the highest GluCEST contrast. Utilizing MR spectroscopic data, in vivo
      GluCEST detection sensitivity (~0.8% mM(-1) ) in subcortical gray matter was
      evaluated and was consistent with the previously reported values. In general, the
      GluCEST map approximates the Glu receptor distribution reported in previous
      positron emission tomography (PET) studies. These findings suggest that high
      resolution GluCEST MRI of subcortical brain structures may prove to be a useful
      tool in diagnosis of brain disorders or treatment responses.

PMID- 23553934
TI  - Cardiac oxidative damage in mice following exposure to nanoparticulate titanium
      dioxide.
AB  - Nanoparticulate titanium dioxide (nano-TiO2 ) is a widely used powerful
      nanoparticulate material with high stability, anticorrosion, and photocatalytic
      property. However, it is possible that during nano-TiO2 exposure, there may be
      negative effects on cardiovascular system in intoxicated mice. The present study
      was therefore undertaken to determine nano-TiO2 -induced oxidative stress and to
      determine whether nano-TiO2 intoxication alters the antioxidant system in the
      mouse heart exposed to 2.5, 5, and 10 mg/kg body weight nano-TiO2 for 90
      consecutive days. The findings showed that long-term exposure to nano-TiO2
      resulted in obvious titanium accumulation in heart, in turn led to sparse cardiac
      muscle fibers, inflammatory response, cell necrosis, and cardiac biochemical
      dysfunction. Nano-TiO2 exposure promoted remarkably reactive oxygen species
      production such as superoxide radicals, hydrogen peroxide, and increased
      malondialdehyde, carbonyl and 8-OHdG levels as degradation products of lipid,
      protein, and DNA peroxidation in heart. Furthermore, nano-TiO2 exposure
      attenuated the activities of antioxidative enzymes, such as superoxide dismutase,
      ascorbate peroxidase, glutathione reductase, glutathione-S-transferase, and
      levels of antioxidants including ascorbic acid, glutathione, and thiol in heart.
      Therefore, TiO2 NPs exposure may impair cardiovascular system in mice, and
      attention should be aroused on the application of nano-TiO2 and their potential
      long-term exposure effects especially on human beings.

PMID- 23553935
TI  - Relationship between severity of liver dysfunction and the relative ratio of
      liver to aortic enhancement (RE) on MRI using hepatocyte-specific contrast.
AB  - PURPOSE: To evaluate differences in liver enhancement among patients with low and
      high morbidity risks and to determine the relationship between severity of liver
      dysfunction and the relative ratio of liver to aortic enhancement (RE) on MRI
      using hepatocyte-specific contrast. MATERIALS AND METHODS: A total of 126
      patients underwent magnetic resonance imaging (MRI) and blood serum testing
      including serology, bilirubin, international normalized ratio, and creatinine
      tests. Radiologists analyzed a region of interest in the liver and aorta on
      precontrast and 10- and 20-minute delayed hepatobiliary phase MR images. Liver
      enhancement after 10 (LE10min ) and 20 minutes (LE20min ) were compared between
      the low- and high-risk groups by independent t-test. Regression analysis was used
      to assess the relationship between the Model for Endstage Liver Disease (MELD)
      score and RE. RESULTS: All 126 patients were classified into either the low-risk
      group (MELD <8; n = 85) or high-risk group (MELD >=8; n = 41). The mean LE10min
      and LE20min were significantly higher in the low-risk group (471.61; 95%
      confidence interval [CI]: 449.79-493.43 and 510.69; 95% CI: 486.51-534.87,
      respectively) than in the high-risk group (401.6776; 95% CI: 364.75-438.61 and
      413.81; 95% CI: 370.91-456.70). There was a moderate inverse correlation between
      MELD score and the relative ratio of liver enhancement (RLE) (r = -0.5442; 95%
      CI: -0.6480 to -0.4207; P<0.01), but a high positive correlation between MELD
      score and RE (r = 0.7470; 95% CI: 0.6665-0.8102; P < 0.01). CONCLUSION: Although
      liver enhancement was significantly greater in low-risk patients compared to high
      risk patients, RE may be a better predictor of liver function than RLE.

PMID- 23553936
TI  - Identification of metal-associated proteins in cells by using continuous-flow gel
      electrophoresis and inductively coupled plasma mass spectrometry.

PMID- 23553937
TI  - Near-infrared polymer light-emitting diodes based on low-energy gap oligomers
      copolymerized into a high-gap polymer host.
AB  - Near-infrared (NIR) polymer light-emitting diodes (PLEDs) based on a fluorene
      dioctyloxyphenylene wide-gap host material copolymerized with a low-gap emitter
      are presented. Various loadings (1, 2.5, 10, 20 mol%) of the low-gap emitter are
      studied, with higher loadings leading to decreased efficiencies likely due to
      aggregation effects. While the 10 mol% loading resulted in almost pure NIR
      emission (>99.6%), the 1 mol% loading yielded optimum device performance, which
      is among the best reported to date for a unblended single-layer pure polymer
      emitter, with an external quantum efficiencies of 0.04% emitting at 909 nm. The
      high spectral purity of the PLEDs combined with their performance support the
      methodology of copolymerization as an effective strategy for developing NIR
      PLEDs.

PMID- 23553938
TI  - Back to the beginning: The initiation of cancer.

PMID- 23553939
TI  - Magic numbers in the solvation of the propofol dimer.

PMID- 23553940
TI  - Sulfiredoxin-1 protects PC12 cells against oxidative stress induced by hydrogen
      peroxide.
AB  - Oxidative stress results in protein oxidation and is implicated in cerebral
      disease, such as Parkinson's disease, Alzheimer's disease, and ischemic stroke.
      Sulfiredoxin-1 (Srxn1) is an endogenous antioxidant protein that has
      neuroprotective effects. The mechanisms of Srxn1 in oxidative stress have not
      been well studied, however. This study used 180 MUM H2 O2 exposure for 24 hr to
      model oxidative stress. This experimental design allowed us to explore the
      protective effects and underlying mechanisms of Srxn1 in PC12 cells. To
      investigate Srxn1's role in oxidative stress protection, transient knockdowns of
      Srxn1 in PC12 cells were performed prior to treatment with 180 MUM H2 O2 for 24
      hr. Knockdown of Srxn1 resulted in decreased cell viability and increased
      cellular damage as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide and lactate dehyrogenase analysis, respectively.
      Intracellular superoxide dismutase and glutathione are important indexes of
      oxidative stress; these were reduced in Srxn1 knockdown PC12. We further found
      that the decreased Srxn1 correlated with a reduction in 2-Cys Prdxs activity.
      Moreover, 2-Cys Prdxs protein levels were increased in the H2 O2 -dosed cells, as
      measured by RT-PCR and immunoblot analysis. These results suggested that Srxn1
      can protect PC12 cells from H2 O2 -induced oxidative stress and are involve in
      Prdxs activity. Srxn1 play a protective role against oxidative injury and
      demonstrates potential as a target for neuroprotective intervention in oxidative
      stress.

PMID- 23553941
TI  - A 25-year experience of endomyocardial biopsy safety in infants.
AB  - OBJECTIVES: To analyze the outcomes and risk factors associated with
      endomyocardial biopsy (EMB) in children less than one year of age. BACKGROUND:
      EMB has proven to be an integral diagnostic tool to evaluate suspected
      myocarditis, identify tumor histology, and provide tissue-graft surveillance
      after cardiac transplantation. The morbidity and mortality of EMB has been well
      established in the adult literature and reviewed in the general pediatric
      population, but there remains limited data for children in the first year of
      life. METHODS: We retrospectively reviewed the cardiology database at our
      institution to identify patients less than one year of age who underwent EMB
      between 1984 and 2008. Cardiac catheterization reports were reviewed for patient
      demographics, biopsy indication, procedural details, and complications. RESULTS:
      A total of 99 EMBs were performed, 49 for evaluation of suspected myocarditis, 43
      for transplant rejection surveillance, 3 to identify tumor histology, and 4 for
      suspected endocardial fibroelastosis. Forty procedures were performed in children
      age < 6 months with 11 complications and 59 procedures performed in children age
      >= 6 months with four complications. In total, there were 12 EMB procedures
      (12.1%) with associated complications: 9 arrhythmias, 4 perforations requiring
      pericardiocentesis, 1 pneumothorax, and 1 death. Univariate analysis revealed a
      significant association between perforation and both weight <8 kg (P = 0.05) and
      age <6 months (P = 0.01). CONCLUSION: Endomyocardial biopsies can be performed
      safely in infants, although children under 6 months of age and less than 8 kg
      represent a high risk group and deserve special consideration due to the
      incidence of complications in this cohort.

PMID- 23553942
TI  - Folding of Top7 in unbiased all-atom Monte Carlo simulations.
AB  - For computational studies of protein folding, proteins with both helical and beta
      sheet secondary structure elements are very challenging, as they expose subtle
      biases of the physical models. Here, we present reproducible folding of a 92
      residue alpha/beta protein (residues 3-94 of Top7, PDB ID: 1QYS) in computer
      simulations starting from random initial conformations using a transferable
      physical model which has been previously shown to describe the folding and
      thermodynamic properties of about 20 other smaller proteins of different folds.
      Top7 is a de novo designed protein with two alpha-helices and a five stranded
      beta-sheet. Experimentally, it is known to be unusually stable for its size, and
      its folding transition distinctly deviates from the two-state behavior commonly
      seen in natural single domain proteins. In our all-atom implicit solvent parallel
      tempering Monte Carlo simulations, Top7 shows a rapid transition to a group of
      states with high native-like secondary structure, and a much slower subsequent
      transition to the native state with a root mean square deviation of about 3.5 A
      from the experimentally determined structure. Consistent with experiments, we
      find Top7 to be thermally extremely stable, although the simulations also find a
      large number of very stable non-native states with high native-like secondary
      structure.

PMID- 23553943
TI  - New RNA purine building blocks, 4'-selenopurine nucleosides: first synthesis and
      unusual mixture of sugar puckerings.
AB  - Writer's blocks: The first synthesis of RNA purine building blocks, 4'
      selenoadenosine and 4'-selenoguanosine was achieved from D-ribose by
      regioisomeric rearrangement, which was confirmed by X-ray crystallography. 4'
      Selenoadenosine exists in an unusual mixture of north and south conformers in the
      solid state.

PMID- 23553944
TI  - Bone stiffness and failure load are related with clinical parameters in men with
      chronic obstructive pulmonary disease.
AB  - Osteoporosis is frequently seen in patients with chronic obstructive pulmonary
      disease (COPD). Because research on bone structure and bone strength in COPD
      patients is limited, the objectives of this pilot study were as follows: (1) to
      compare bone structure, stiffness, and failure load, measured at the peripheral
      skeleton, between men with and without COPD after stratification for areal bone
      mineral density (aBMD); and (2) to relate clinical parameters with bone stiffness
      and failure load in men with COPD. We included 30 men with COPD (normal aBMD, n =
      18; osteoporosis, n = 12) and 17 men without COPD (normal aBMD, n = 9;
      osteoporosis, n = 8). We assessed pack-years of smoking, body mass index (BMI),
      fat free mass index (FFMI), pulmonary function (forced expiratory volume in 1
      second [FEV1 ], FEV1 /forced vital capacity [FVC], diffusion capacity for carbon
      monoxide [DLCO], and transfer coefficient for carbon monoxide [KCO]), and extent
      of emphysema. Bone structure of the distal radius and tibia was assessed by high
      resolution peripheral quantitative computed tomography (HR-pQCT), and bone
      stiffness and failure load of the distal radius and tibia were estimated from
      micro finite element analysis (uFEA). After stratification for aBMD and COPD, men
      with osteoporosis showed abnormal bone structure (p < 0.01), lower bone stiffness
      (p < 0.01), and lower failure load (p < 0.01) compared with men with normal aBMD,
      and men with COPD had comparable bone structure, stiffness, and failure load
      compared with men without COPD. In men with COPD, lower FFMI was related with
      lower bone stiffness, and failure load of the radius and tibia and lower DLCO and
      KCO were related with lower bone stiffness and failure load of the tibia after
      normalization with respect to femoral neck aBMD. Thus, this pilot study could not
      detect differences in bone structure, stiffness, and failure load between men
      with and without COPD after stratification for aBMD. FFMI and gas transfer
      capacity of the lung were significantly related with bone stiffness and failure
      load in men with COPD after normalization with respect to femoral neck aBMD.

PMID- 23553945
TI  - Adiabatic multi-echo 31P spectroscopic imaging (AMESING) at 7 T for the
      measurement of transverse relaxation times and regaining of sensitivity in
      tissues with short T2 values.
AB  - An adiabatic multi-echo spectroscopic imaging (AMESING) sequence, used for (31) P
      MRSI, with spherical k-space sampling and compensated phase-encoding gradients,
      was implemented on a whole-body 7-T MR system. One free induction decay (FID) and
      up to five symmetric echoes can be acquired with this sequence. In tissues with
      low T2 and high T2 , this can theoretically lead to a potential maximum signal-to
      noise ratio (SNR) increase of almost a factor of three, compared with a
      conventional FID acquisition with Ernst-angle excitation. However, with T2 values
      being, in practice, <=400 ms, a maximum enhancement of approximately two compared
      with low flip Ernst-angle excitation should be feasible. The multi-echo sequence
      enables the determination of localized T2 values, and was validated with (31) P
      three-dimensional MRSI on the calf muscle and breast of a healthy volunteer, and
      subsequently applied in a patient with breast cancer. The T2 values of
      phosphocreatine, phosphodiesters (PDE) and inorganic phosphate in calf muscle
      were 193 +/- 5 ms, 375 +/- 44 ms and 96 +/- 10 ms, respectively, and the apparent
      T2 value of gamma-ATP was 25 +/- 6 ms. A T2 value of 136 +/- 15 ms for inorganic
      phosphate was measured in glandular breast tissue of a healthy volunteer. The T2
      values of phosphomonoesters (PME) and PDE in breast cancer tissue (ductulolobular
      carcinoma) ranged between 170 and 210 ms, and the PME to PDE ratios were
      calculated to be phosphoethanolamine/glycerophosphoethanolamine = 2.7,
      phosphocholine/glycerophosphocholine = 1.8 and PME/PDE = 2.3. Considering the
      relatively short T2 values of the metabolites in breast tissue at 7 T, the echo
      spacing can be short without compromising spectral resolution, whilst maximizing
      the sensitivity.

PMID- 23553946
TI  - MicroRNA-126 regulates EPCs function: implications for a role of miR-126 in
      preeclampsia.
AB  - Preeclampsia is a specific vascular complication in pregnancy, which has a
      pathophysiology of altered endothelial homeostasis. There is extensive evidence
      that endothelial progenitor cells (EPCs) dysfunction underlies the endothelial
      cells loss that occurs during preeclampsia. MicroRNA-126 (miR-126), an
      angiogenesis-related miRNA, has been shown to have potential angiogenic effects
      both in cultured endothelial cells in vitro and ischemia-induced angiogenesis in
      vivo. However, whether miR-126 has therapeutic potential in placental
      vasculogenesis of preeclampsia remains unclear. In this report, we analyzed the
      EPCs number and expression of miR-126 in patients with preeclampsia, then
      investigated the effects of miR-126 on EPCs function and rat placenta by
      employing up-regulation and down-regulation strategies. We confirmed that miR-126
      enhanced EPCs proliferation, differentiation and migration. However, a strong
      reduction in EPCs function was observed in vitro after miR-126 inhibitor
      transfection. MiR-126 exerts pro-angiogenic functions by suppressing the
      synthetize of antiangiogenic factors PIK3R2. Similar to miR-126 overexpression,
      PIK3R2 downregulation promoted EPCs function. In pregnant rats, we also found
      that miR-126 increased vascular sprouting, placenta and fetus weights. These
      findings suggest that miR-126 is essential for angiogenic properties of EPCs in
      vitro and placental vasculogenesis in vivo, providing basis for an alternative
      therapeutic approach in patients with preeclampsia.

PMID- 23553947
TI  - Guillaume Rondelet (1507-1566): Cardinal physician and anatomist who dissected
      his own son.
AB  - The 16th century French anatomist Guillaume Rondelet will be remembered as a
      great naturalist and a founder of ichthyology. Little known to most is that
      Rondelet was a proficient anatomist and contemporary to Vesalius and in fact,
      both studied anatomy under Johannes Guinter. Even less known is that he
      established the first dissecting theatre at Montpellier and it was here that he
      would dissect his infant son in an attempt to identify the cause of death. In
      this article, we review the life and contributions to anatomy of Rondelet.

PMID- 23553948
TI  - BAX/BCL2 RMFI ratio predicts better induction response in pediatric patients with
      acute myeloid leukemia.
AB  - BAX/BCL2 ratio in pediatric AML has not been evaluated. In this first prospective
      study, we evaluated BAX/BCL2 transcript and RMFI ratio in 64 patients using real
      time PCR (TaqMan Probe chemistry) and flow-cytometry, respectively. There was no
      correlation of BAX/BCL2 transcript ratio with RMFI ratio (R = -0.05; P = 0.715).
      Patients with WBC count >50,000/mm(3) had lower BAX/BCL2 RMFI ratio (P = 0.043),
      whereas no difference in ratio was observed among patients of different
      cytogenetics subgroups (P = 0.786). Higher BAX/BCL2 RMFI ratio was associated
      positively with CR rate (P = 0.03), but this study was unable to show that it
      translated into improved EFS or OS.

PMID- 23553949
TI  - Triple echo steady-state (TESS) relaxometry.
AB  - PURPOSE: Rapid imaging techniques have attracted increased interest for
      relaxometry, but none are perfect: they are prone to static (B0 ) and transmit
      (B1 ) field heterogeneities, and commonly biased by T2 /T1 . The purpose of this
      study is the development of a rapid T1 and T2 relaxometry method that is
      completely (T2 ) or partly (T1 ) bias-free. METHODS: A new method is introduced
      to simultaneously quantify T1 and T2 within one single scan based on a triple
      echo steady-state (TESS) approach in combination with an iterative golden section
      search. TESS relaxometry is optimized and evaluated from simulations, in vitro
      studies, and in vivo experiments. RESULTS: It is found that relaxometry with TESS
      is not biased by T2 /T1 , insensitive to B0 heterogeneities, and, surprisingly,
      that TESS-T2 is not affected by B1 field errors. Consequently, excellent
      correspondence between TESS and reference spin echo data is observed for T2 in
      vitro at 1.5 T and in vivo at 3 T. CONCLUSION: TESS offers rapid T1 and T2
      quantification within one single scan, and in particular B1 -insensitive T2
      estimation. As a result, the new proposed method is of high interest for fast and
      reliable high-resolution T2 mapping, especially of the musculoskeletal system at
      high to ultra-high fields.

PMID- 23553950
TI  - The surface microporosity of ceramic biomaterials influences the resorption
      capacity of osteoclasts.
AB  - This study investigated the influence of the surface microporosity of beta-tri
      calcium phosphate (beta-TCP) ceramics on the resorption capacity of osteoclasts.
      This was achieved by first compacting commercially available beta-TCP powder into
      disks that were sintered at various temperatures, thereby yielding different
      surface microporosities. Scanning electron microscopy (SEM) and subsequent image
      processing verified different degrees of surface microporosity on the disks.
      Rabbit osteoclasts in a bone marrow derived cell suspension were then seeded onto
      these disks and incubated for 48 h. Tartrate resistant acid phosphatase (TRAP)
      staining confirmed the presence of osteoclasts on all disks. Actin ring staining
      that detected actively resorbing OCs showed an inverse linear correlation between
      the number of actively resorbing osteoclasts (percentage of total OCs on the
      surfaces) with surface microporosity. These findings should be taken into
      consideration for the design and/or production of new beta-TCP bone graft
      substitutes.

PMID- 23553951
TI  - PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial
      wound healing.
AB  - Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic
      method for patients with LSC deficiency. The maintenance of stem cell
      characteristics in the process of culture expansion is critical for the success
      of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF)
      increased the numbers of holoclone in LSC monolayer culture and preserved the
      stemness of LSC in suspension culture by evidence of DeltaNp63alpha, Bmi-1, and
      ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF
      stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was
      capable of increasing the numbers of DeltaNp63alpha-positive cells. The mitogenic
      effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and
      STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78-121) was as effective as the
      full length PEDF in LSC expansion in suspension culture and limbal equivalent
      formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to
      mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound
      healing. Microscopically, 44-mer PEDF advanced the early proliferative response
      in limbus, increased the proliferation of DeltaNp63alpha-positive cells both in
      limbus and in epithelial healing front, and assisted the repopulation of limbus
      in the late phase of wound healing. In conclusion, the capability of expanding
      LSC in cell culture and in animal indicates the potential of PEDF and its
      fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and
      their uses as therapeutics for treating corneal wound.

PMID- 23553952
TI  - Aromatic C=C bonds as dipolarophiles: facile reactions of uncomplexed electron
      deficient benzene derivatives and other aromatic rings with a non-stabilized
      azomethine ylide.
AB  - Non-stabilized azomethine ylide 4a reacts smoothly at room temperature with a
      variety of uncomplexed aromatic heterocycles and carbocycles on the condition
      that the ring contains at least one or two electron-withdrawing substituents,
      respectively. Aromatic substrates, including pyridine and benzene derivatives,
      participate as 2pi components in [3+2] cycloaddition reactions and interact with
      one, two, or three equivalent(s) of the ylide, depending on their structure and
      substitution pattern. Thus, this process affords highly functionalized polycyclic
      structures that contain between one and three pyrrolidinyl ring(s) in useful
      yields. These results indicate that the site selectivity of the cycloaddition
      reactions strongly depends on both the nature and the positions of the
      substituents. In most cases, the second 1,3-dipolar reaction occurs on the
      opposite face to the one that contains the first pyrrolidinyl ring. DFT
      calculations on model compounds indicate that a concerted mechanism features a
      low activation barrier.

PMID- 23553954
TI  - Surface morphology and wettability of sandblasted PEEK and its composites.
AB  - PolyEtherEtherKetone (PEEK) is an advanced high-performance thermoplastic
      polymer, and its composites are used extensively in the aeronautical industry.
      This paper presents an experimental approach to determine the role of
      sandblasting treatment on surface morphology modifications of PEEK and its
      composites, with the aim of developing a topographic characterization in order to
      propose pertinent parameters that correlate with contact angles from wettability
      measurement. Sandblasting (fine abrasive particle projection) was selected as the
      surface treatment, in order to obtain various morphologically quasi-isotropic
      surfaces. Two surface metrological approaches to topographical characterization
      were used to correlate the wettability behavior with the surface roughness
      parameters, the first based on 2D profile analysis and the second on 3D
      topography analysis. Two different unreinforced grades of PEEK and four
      composites: discontinuous carbon fiber or glass fiber-reinforced, oriented, and
      unoriented, were studied. The experimental results indicated the sandblasting
      process duration necessary to reach a morphological steady state. It was stated
      that one of the pertinent parameters is the mean slope of roughness motif in 2D
      profile characterization, as confirmed by previous findings for anisotropic
      morphologies. However, for all cases, a new topographic parameter Sr , combining
      the surface amplitude and the summit density distribution, is proposed as a
      factor well-correlated with wettability characteristics.

PMID- 23553953
TI  - Awareness and coping with emotion in schizophrenia: acceptability, feasibility
      and case illustrations.
AB  - Although current treatments help to alleviate some of the symptoms of
      schizophrenia, people with schizophrenia often continue to experience residual
      symptoms. An emotion-focused treatment approach may help to improve well-being in
      this population by increasing positive experiences and resources. In this
      article, we discuss the feasibility and acceptability of a skills-based group
      treatment for people schizophrenia or schizoaffective disorder. As part of the
      Awareness and Coping with Emotion in Schizophrenia (ACES) intervention, group
      members learned eight empirically supported cognitive and behavioural skills
      covering emotional awareness and coping. Group member feedback and three case
      illustrations illuminate participants' experiences with the group, as well as the
      potential benefits and challenges of this treatment approach. These data suggest
      that ACES is a feasible and acceptable group intervention. Future research is
      needed to examine whether ACES has a selective impact on well-being, but these
      initial findings point to the promise of this intervention to improve quality of
      life for individuals with schizophrenia and schizoaffective disorder, thus
      filling a void in existing treatments options. KEY PRACTITIONER MESSAGE: There is
      a void in existing treatments for schizophrenia with few interventions focusing
      on increasing well-being in this population. Awareness and Coping with Emotion in
      Schizophrenia (ACES) is a skills-based group intervention that teaches cognitive
      and behavioural interventions to promote awareness and coping with emotion.
      Preliminary evidence demonstrates the feasibility and acceptance of the ACES
      group intervention in increasing well-being in those with schizophrenia. Future
      studies should extend this work by systematically evaluating the efficacy of this
      treatment approach.

PMID- 23553955
TI  - Exploring the issue of employment for adults with an intellectual disability in
      Ireland.
AB  - BACKGROUND: The benefits of being in employment are well documented; however,
      underemployment is a critical issue for people with intellectual disability (ID).
      Some individuals perceive themselves as being in employment when in fact they are
      attending a non-work site such as a day service. The impact that this perception
      of employment has on other areas in life has not been investigated and research
      into this area could have implications for both policy makers and service
      providers. MATERIALS AND METHODS: The first wave of the intellectual disability
      Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) included a
      series of questions on employment that yielded data for a representative sample
      of 753 participants with intellectual disability aged 40 and over randomly
      selected from Ireland's National Intellectual Disability Database (NIDD). RESULTS
      AND DISCUSSION: Overall, 6.6% of the population were in real paid employment,
      7.4% in perceived employment, 12% in sheltered employment and 73.5% were
      unemployed. Differences were identified between these two groups in relation to
      social activities, levels of depression and self-rated health. Further
      investigation is needed into the area of perceived employment.

PMID- 23553956
TI  - A three-component palladium-catalyzed oxidative C-C coupling reaction: a domino
      process in two dimensions.

PMID- 23553957
TI  - A framework for assessing cumulative effects in watersheds: an introduction to
      Canadian case studies.
AB  - From 2008 to 2013, a series of studies supported by the Canadian Water Network
      were conducted in Canadian watersheds in an effort to improve methods to assess
      cumulative effects. These studies fit under a common framework for watershed
      cumulative effects assessment (CEA). This article presents an introduction to the
      Special Series on Watershed CEA in IEAM including the framework and its impetus,
      a brief introduction to each of the articles in the series, challenges, and a
      path forward. The framework includes a regional water monitoring program that
      produces 3 core outputs: an accumulated state assessment, stressor-response
      relationships, and development of predictive cumulative effects scenario models.
      The framework considers core values, indicators, thresholds, and use of
      consistent terminology. It emphasizes that CEA requires 2 components, accumulated
      state quantification and predictive scenario forecasting. It recognizes both of
      these components must be supported by a regional, multiscale monitoring program.

PMID- 23553958
TI  - Ellagic acid and derivatives from Cochlospermum angolensis Welw. Extracts: HPLC
      DAD-ESI/MS(n) profiling, quantification and in vitro anti-depressant, anti
      cholinesterase and anti-oxidant activities.
AB  - INTRODUCTION: Cochlospermum angolensis Welw. bark is a medicinal plant consumed
      for the treatment of hepatic diseases and for the prophylaxis of malaria.
      Nevertheless, there are few studies concerning its chemical composition and
      biological potential. OBJECTIVE: Since phenolic compounds are described as
      powerful anti-oxidants and neuroprotective agents, the purpose of this study was
      to characterise the phenolic profile of this species and to extend the knowledge
      on its medicinal properties, namely its potential against oxidative stress,
      Alzheimer's disease and depression. METHODS: The phenolic composition of aqueous
      and hydromethanolic extracts was characterised by HPLC-DAD-ESI/MS(n) . Anti
      radical potential was tested against 2,2-diphenyl-1-picrylhdrazyl, superoxide
      anion and nitric oxide radicals, and neuroprotective effect was assessed against
      acetylcholinesterase, butyrylcholinesterase and monoamine oxidase A. RESULTS:
      Eight compounds were characterised for the first time. Hydromethanolic extract
      was richer in methyl ellagic acid and its derivatives, while aqueous extract had
      higher amounts of ellagic acid and its derivatives. Methyl ellagic acid pentoside
      isomer and ellagic acid were the major compounds in the two extracts,
      respectively. Both extracts and ellagic acid revealed radical scavenging capacity
      stronger than that of ascorbic acid, but a weak effect on cholinesterases was
      observed. Their anti-depressant activity was also very strong. CONCLUSION: The
      results provided evidence of the value of C. angolensis as a source of health
      promoting anti-oxidants and anti-depressant compounds, with potential to be used
      as a raw product for food and pharmaceutical industries.

PMID- 23553959
TI  - Promotion of mouse ameloblast proliferation by Lgr5 mediated integrin signaling.
AB  - Rodent incisors grow throughout the animal's lives, and the tooth-forming cells
      are provided from proximal ends of the incisors where the tooth epithelium forms
      a stem cell niche called cervical loop. The committing cells in a cervical loop
      actively begin to proliferate (pre-ameloblasts), and differentiating into
      ameloblasts. This study showed that the lower incisors of mice null for CD61
      (CD61(-/-) ), also known as integrin beta3, were significantly shorter than those
      of the wild-type mice at 8-week-old. The protein and mRNA expressions levels of
      Fgfr2, Lgr5, and Notch1, which are known to be involved in pre-ameloblastic cell
      proliferation and stem cell maintenance, were reduced in the cervical loop of 2
      week-old CD61(-/-) mice. The proliferation of pre-ameloblasts was reduced in
      CD61(-/-) ameloblasts. The siRNA-mediated suppression of CD61 (siCD61) reduced
      the proliferation of pre-ameloblastic cell line ALC, and the expression levels of
      Lgr5 and Notch1 were reduced by the transfection with siCD61. The suppression of
      Lgr5 by transfection with siLgr5 suppressed the proliferation of the ALC cells.
      These results suggested that CD61 signaling is required for the proper growth of
      the cervical loop and for the promotion of the proliferation of pre-ameloblastic
      cells through Lgr5.

PMID- 23553960
TI  - AKT primes snail-induced EMT concomitantly with the collective migration of
      squamous cell carcinoma cells.
AB  - In this study, we found that wounding of a confluent monolayer of squamous cell
      carcinoma (SCC) cells induced epithelial-mesenchymal transition (EMT)
      specifically at the edge of the wound. This process required the combined
      stimulation of TGFbeta, TNFalpha, and PDGF-D. Such a combined cytokine treatment
      of confluent monolayers of the cells upregulated the expression levels of Snail
      and Slug via PI3K. The PI3K downstream effector, AKT, was dispensable for the
      upregulation of Snail and Slug, but essential for enabling EMT in response to
      upregulation of Snail and Slug.

PMID- 23553961
TI  - In situ study of CO oxidation on HOPG-supported Pt nanoparticles.

PMID- 23553962
TI  - Skeletal health in long-duration astronauts: nature, assessment, and management
      recommendations from the NASA Bone Summit.
AB  - Concern about the risk of bone loss in astronauts as a result of prolonged
      exposure to microgravity prompted the National Aeronautics and Space
      Administration to convene a Bone Summit with a panel of experts at the Johnson
      Space Center to review the medical data and research evidence from astronauts who
      have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts
      who had served on spaceflight missions lasting between 120 and 180 days with
      attention focused on astronauts who (1) were repeat fliers on long-duration
      missions, (2) were users of an advanced resistive exercise device (ARED), (3)
      were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip
      bone strength estimated by finite element modeling, or (5) had lost >10% of areal
      bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy
      X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the
      effects of spaceflight on bone strength, the panel recommended that the U.S.
      space program use QCT and finite element modeling to further study the unique
      effects of spaceflight (and recovery) on bone health in order to better inform
      clinical decisions.

PMID- 23553963
TI  - CYP1A expression in liver and gills of roach (Rutilus rutilus) after waterborne
      exposure to two phenanthrene derivatives, 1-methylphenanthrene and 4
      methylphenanthrene.
AB  - Phenanthrenes (Phs) substituted with alkyl groups are a class of compound present
      in the environment, and they appear to be toxic to developing fish. The present
      study aimed to investigate the effect of waterborne exposure to two monomethyl
      derivatives of phenanthrene, 1-methylphenanthrene (1M-Ph) and 4
      methylphenanthrene (4M-Ph), on cytochrome P450 1A (CYP1A) gene expression in fish
      gills and liver. Juvenile common roaches (Rutilus rutilus) were exposed to water
      with dimethyl sulfoxide (DMSO) solutions of 1M-Ph, 4M-Ph, benzo[a]pyrene (BaP;
      positive control), each at a dose of 100 ug/L, or to water with DMSO alone
      (negative control group) for 2 d and 7 d. Significant CYP1A responses with regard
      to treatment and exposure duration were noted (2-way analysis of variance
      [ANOVA]) in gills (p = 0.013 and p = 0.003, respectively) and liver (p < 0.001).
      The 2 monomethyl Phs did not induce consistent gene expression changes, except
      for 4-MPh, which elevated the CYP1A messenger ribonucleic acid (mRNA) level in
      the liver at the end of the treatment (almost 4-fold; p < 0.05; 7 d). As was
      expected, exposure to BaP resulted in elevation of CYP1A mRNA expression in
      treated fish compared with the control group. Expressions after 2 d and 7 d were
      approximately 220- and 180-fold higher in liver and 8- and 6-fold higher in gills
      respectively. The CYP1A protein levels remained stable in both tissues, with one
      notable exception in roach liver treated for 2 d with BaP (~ 6-fold increase; p <
      0.05). The different effects of the 1- and 4-methylphenanthrenes on CYP1A gene
      expression in roach liver suggest a relationship between chemical or 3-D
      structure of the differentially substituted monomethyl Phs and their biological
      activity.

PMID- 23553964
TI  - Animal studies on medicinal herbs: predictability, dose conversion and potential
      value.
AB  - Animal studies testing medicinal herbs are often misinterpreted by both
      translational researchers and clinicians due to a lack of information regarding
      their predictability, human dose equivalent and potential value. The most common
      mistake is to design or translate an animal study on a milligram per kilogram
      basis. This can lead to underestimation of the toxicity and/or overestimation of
      the amount needed for human therapy. Instead, allometric scaling, which involves
      body surface area, should be used. While the differences in the pharmacokinetic
      and pharmacodynamic phases between species will inevitably lead to some degree of
      error in extrapolation of results regardless of the conversion method used,
      correct design and interpretation of animal studies can provide information that
      is not able to be provided by in vitro studies, computer modeling or even
      traditional use.

PMID- 23553965
TI  - Crystal structure of the invertebrate bifunctional purine biosynthesis enzyme
      PAICS at 2.8 A resolution.
AB  - Two important steps of the de novo purine biosynthesis pathway are catalyzed by
      the 5-aminoimidazole ribonucleotide carboxylase and the 4-(N-succinylcarboxamide)
      5-aminoimidazole ribonucleotide synthetase enzymes. In most eukaryotic organisms,
      these two activities are present in the bifunctional enzyme complex known as
      PAICS. We have determined the 2.8-A resolution crystal structure of the 350-kDa
      invertebrate PAICS from insect cells (Trichoplusia ni) using single-wavelength
      anomalous dispersion methods. Comparison of insect PAICS to human and prokaryotic
      homologs provides insights into substrate binding and reveals a highly conserved
      enzymatic framework across divergent species.

PMID- 23553966
TI  - Asymptomatic isolated partial hiatal herniation of the pancreas: MDCT evaluation
      and anatomical explanation: case report and review of literature.
AB  - Isolated herniation of the pancreas through a gastroesophageal hiatus is an
      extremely rare condition, and only one case has been reported in the world
      literature. We describe a MDCT diagnosis of isolated partial hiatal hernia
      containing the body of a normal pancreas in an asymptomatic patient, give an
      anatomical explanation and review the corresponding literature.

PMID- 23553967
TI  - Respiratory-induced 3D deformations of the renal arteries quantified with
      geometric modeling during inspiration and expiration breath-holds of magnetic
      resonance angiography.
AB  - PURPOSE: To quantify renal artery deformation due to respiration using magnetic
      resonance (MR) image-based geometric analysis. MATERIALS AND METHODS: Five males
      were imaged with contrast-enhanced MR angiography during inspiratory and
      expiratory breath-holds. From 3D models of the abdominal aorta, left and right
      renal arteries (LRA and RRA), we quantified branching angle, curvature, peak
      curve angle, axial length, and locations of branch points. RESULTS: With
      expiration, maximum curvature changes were 0.054 +/- 0.025 mm(-1) (P < 0.01), and
      curve angle at the most proximal curvature peak increased by 8.0 +/- 4.5 degrees 
      (P < 0.05) in the LRA. Changes in maximum curvature and curve angles were not
      significant in the RRA. The first renal bifurcation point translated superiorly
      and posteriorly by 9.7 +/- 3.6 mm (P < 0.005) and 3.5 +/- 2.1 mm (P < 0.05),
      respectively, in the LRA, and 10.8 +/- 6.1 mm (P < 0.05) and 3.6 +/- 2.5 mm (P <
      0.05), respectively, in the RRA. Changes in branching angle, axial length, and
      renal ostia locations were not significant. CONCLUSION: The LRA and RRA deformed
      and translated significantly. Greater deformation of the LRA as compared to the
      RRA may be due to asymmetric anatomy and mechanical support by the inferior vena
      cava. The presented methodology can extend to quantification of deformation of
      diseased and stented arteries to help renal artery implant development.

PMID- 23553968
TI  - Percutaneous ventricular septal defect closure with Amplatzer devices resulting
      in severe tricuspid regurgitation.
AB  - While percutaneous intervention is an alternative for patients who are not
      surgical candidates, the rate of morbidity and mortality is comparable to open
      repair. Appending the reported complications associated with percutaneous
      intervention (device mal-positioning, dislodgement, and entrapment in the sub
      valvular apparatus), we report mechanical damage to the tricuspid valve (TV).
      Percutaneous closure with an Amplatzer septal occluder device was attempted on
      three patients who developed a ventricular septal defects (VSD) after myocardial
      infarction. In all three cases, damage to the tricuspid leaflet was noted post
      procedure. The accompanying severe tricuspid regurgitation led to right
      ventricular failure, even in the patients where the VSD was considered
      successfully occluded. Despite successful deployment of the Amplatzer device,
      complications with catheter manipulation may still arise. Damage to the TV can
      occur during percutaneous VSD closure with Amplatzer device. Periprocedure TEE
      monitoring can detect damage to the tricuspid leaflets.

PMID- 23553969
TI  - Structural and functional characterization of peptides derived from the carboxy
      terminal region of a defensin from the tick Ornithodoros savignyi.
AB  - Tick defensins may serve as templates for the development of multifunctional
      peptides. The purpose of this study was to evaluate shorter peptides derived from
      tick defensin isoform 2 (OsDef2) in terms of their antibacterial, antioxidant,
      and cytotoxic activities. We compared the structural and functional properties of
      a synthetic peptide derived from the carboxy-terminal of the parent peptide (Os)
      to that of an analogue in which the three cysteine residues were omitted (Os-C).
      Here, we report that both peptides were bactericidal (MBC values ranging from
      0.94-15 ug/ml) to both Gram-positive and Gram-negative bacteria, whereas the
      parent peptide only exhibited Gram-positive antibacterial activity. The Os
      peptide was found to be two-fold more active than Os-C against three of the four
      tested bacteria but equally active against Staphylococcus aureus. Os showed rapid
      killing kinetics against both Escherichia coli and Bacillus subtilis, whereas Os
      C took longer, suggesting different modes of action. Scanning electron microscopy
      showed that in contrast to melittin for which blebbing of bacterial surfaces was
      observed, cells exposed to either peptide appeared flattened and empty. Circular
      dichroism data indicated that in a membrane-mimicking environment, the cysteine
      containing peptide has a higher alpha-helical content. Both peptides were found
      to be non-toxic to mammalian cells. Moreover, the peptides displayed potent
      antioxidant activity and were 12 times more active than melittin. Multifunctional
      peptides hold potential for a wide range of clinical applications and further
      investigation into their mode of antibacterial and antioxidant properties is
      therefore warranted.

PMID- 23553970
TI  - Method to help ensure survival of a very small skin paddle of pectoralis major
      musculocutaneous flap in head and neck reconstruction.
AB  - BACKGROUND: When the required dimension of skin paddle of a pectoralis major
      musculocutaneous (PMMC) flap is very small, its survival often becomes
      questionable. We introduce a simple technique which enlarges the practical
      dimension of a very small skin paddle, leading to ensure the survival of a PMMC
      flap. METHOD AND RESULT: A PMMC flap size of 1.5 * 4 cm was required for repair
      of leakage which developed 2 weeks after the primary ablative surgery for
      hypopharyngeal cancer. The skin paddle was designed in the size of 4.5 * 7 cm and
      was deepithelized except the original dimension. After the skin edge was sutured
      to the defect margin, the deepithelized dermal portion covered the repair site to
      enhance the suture. CONCLUSION: The effective dimension of a very small skin
      paddle can be quite enlarged thus increasing the possibility of capturing
      perforators. This could decrease the risk of avulsion during flap transfer and
      provide backing of the repair site.

PMID- 23553971
TI  - When to remeasure cardiovascular risk in untreated people at low and intermediate
      risk: observational study.
AB  - OBJECTIVE: To estimate the probability of becoming high risk for cardiovascular
      disease among people at low and intermediate risk and not being treated for high
      blood pressure or lipid levels. DESIGN: Observational study. SETTING: General
      communities in Japan and the United States. PARTICIPANTS: 13,757 participants of
      the Tokyo health check-up study and 3855 of the Framingham studies aged 30-74
      years with complete data on risk equation covariates, not receiving blood
      pressure or cholesterol lowering treatment, and with an estimated risk of
      cardiovascular disease <20% within 10 years. We stratified participants on the
      basis of baseline risk: <5%, 5-<10%, 10-<15%, and 15-<20%.We used follow-up
      measurements from the Tokyo study done annually over three years (2006-10) and
      follow-up visits in the Framingham study done between eight (1968-75) and 19
      years (1990-1995) after baseline. MAIN OUTCOME MEASURE: Estimated 10 year risk of
      a cardiovascular event >20% using the Framingham equation. RESULTS: At baseline
      most participants had <5% risk (60.6% of Tokyo cohort and 45.7% of Framingham
      cohort) or 5-<10% risk (24.0% and 28.0%, respectively) of a cardiovascular event
      within 10 years. There was <10% probability of crossing the treatment threshold
      at 19, 8, and 3 years for baseline risk groups <5%, 5-<10%, and 10-<15%,
      respectively, and >10% probability of crossing the treatment threshold at one
      year for the 15-<20% baseline risk group. CONCLUSIONS: Decisions on the frequency
      of remeasuring for cardiovascular risk should be made on the basis of baseline
      risk. Repeat risk estimation before 8-10 years is not warranted for most people
      initially not requiring treatment. However, remeasurement within a year seems
      warranted in those with an initial 15-<20% risk.

PMID- 23553972
TI  - Lessons from patients' journeys.

PMID- 23553973
TI  - A mass in the liver.

PMID- 23553974
TI  - Take me to your leader.

PMID- 23553975
TI  - Debilitated smokers tell their stories in graphic US antismoking campaign.

PMID- 23553976
TI  - Twenty one Bahraini medical professionals overturn convictions for anti
      government protest.

PMID- 23553977
TI  - Interpreting an isolated raised serum alkaline phosphatase level in an
      asymptomatic patient.

PMID- 23553978
TI  - Interaction between ganglioside G(M1) and diosgenin in langmuir monolayers at the
      air/water interface.
AB  - The interaction between ganglioside GM1 (GM1) and diosgenin (Dios) in mixed
      monolayers was investigated using surface pressure measurements and atomic force
      microscopy (AFM). The miscibility and stability of the mixed monolayer was
      evaluated both in a qualitative and quantitative way in terms of the excess mean
      molecular area (DeltaAex), excess Gibbs energy (DeltaGex). The DeltaAex of mixed
      GM1/Dios monolayer was found to have positive deviations from ideality at low
      Dios mole fractions (XDios = 0.2). Above XDios = 0.2, there was a marked negative
      deviation from ideal mixing, indicating attractive interaction between G(M1) and
      Dios. According to the values of excess Gibbs energy of mixing monolayers, the
      more stable monolayers assayed was: XDios = 0.6. The compressibility coefficient
      was assessed at various surface pressures. The monolayer of Dios was more
      elasticity or rigid than G(M1). The AFM images for the mixed monolayers at 30
      mN/m indicated there was obvious phase separation in the mixed monolayers. These
      findings will provide useful information for understanding the interaction
      between drug and lipids.

PMID- 23553979
TI  - Functional improvement in hospitalized older adults is independent of dementia
      diagnosis: experience of a specialized delirium management unit.
AB  - BACKGROUND: Patients with delirium, especially when superimposed on dementia, are
      at high risk of functional decline. OBJECTIVE: To examine the influence of a
      multicomponent delirium management program, the geriatric monitoring unit (GMU),
      on functional progress of delirious older patients and the impact of underlying
      dementia on functional recovery. DESIGN: Prospective cohort study. SETTING: The
      GMU is a specialized 5-bed unit for the care of delirious older adults within an
      acute tertiary hospital. PATIENTS: Patients aged 65 years and older with
      delirium. INTERVENTION: The GMU is a multifactorial delirium treatment program
      with core interventions focusing on early mobilization and rehabilitation.
      MEASUREMENTS: Baseline measures included delirium severity (Delirium Rating Scale
      98 and Confusion Assessment Method severity), Chinese Mini-Mental State
      Examination, functional status (modified Barthel Index [MBI]), comorbidity
      (Charlson's), and illness severity (modified Severity of Illness Index). Patients
      with and without dementia were compared for recovery in cognitive scores and
      functional status. RESULTS: Of 122 patients with delirium who were admitted to
      the GMU over a 1-year period, 82 (67.2%) had underlying dementia. There were no
      significant differences in age, gender, delirium severity, illness severity,
      cognitive performance, and functional status at admission to the GMU between
      groups, although patients with dementia had significantly higher comorbidity
      (Charlson's 2.27 vs 1.75, P = 0.05). Significant cognitive and functional
      improvement was observed for the entire GMU cohort, with demented and nondemented
      groups capable of functional recovery (MBI gain of 20.43 vs 17.35, respectively,
      P = 0.35). CONCLUSION: Elderly patients with dementia recovering from delirium
      have comparable potential for functional recovery as their cognitively intact
      counterparts in a delirium management unit focused on geriatric nursing care and
      rehabilitation.

PMID- 23553980
TI  - The American society of pediatric hematology/oncology (ASPHO) 2013 distinguished
      career award goes to Dr. Gregory H. Reaman.

PMID- 23553981
TI  - Noninvasive assessment of osteoarthritis severity in human explants by
      multicontrast MRI.
AB  - PURPOSE: Medical imaging has the potential to noninvasively diagnose early
      disease onset and monitor the success of repair therapies. Unfortunately, few
      reliable imaging biomarkers exist to detect cartilage diseases before advanced
      degeneration in the tissue. METHOD: In this study, we quantified the ability to
      detect osteoarthritis (OA) severity in human cartilage explants using a
      multicontrast magnetic resonance imaging (MRI) approach, inclusive of novel
      displacements under applied loading by MRI, relaxivity measures, and standard
      MRI. RESULTS: Displacements under applied loading by MRI measures, which
      characterized the spatial micromechanical environment by 2D finite and Von Mises
      strains, were strong predictors of histologically assessed OA severity, both
      before and after controlling for factors, e.g., patient, joint region, and
      morphology. Relaxivity measures, sensitive to local macromolecular weight and
      composition, including T1rho, but not T1 or T2, were predictors of OA severity. A
      combined multicontrast approach that exploited spatial variations in tissue
      biomechanics and extracellular matrix structure yielded the strongest
      relationships to OA severity. CONCLUSION: Our results indicate that combining
      multiple MRI-based biomarkers has high potential for the noninvasive measurement
      of OA severity and the evaluation of potential therapeutic agents used in the
      treatment of early OA in animal and human trials.

PMID- 23553982
TI  - New hydrogel obtained from a novel dendritic monomer as a promising candidate for
      biomedical applications.
AB  - Acid functional hydrogels are a type of materials with many advantages. Over the
      last years, increasing attention for the synthesis of dendronized polymers has
      been drawn due to their unique properties of high multivalence in the same
      surface as compared with conventional polymers. In this study, we report the
      preparation of novel acid dendronized hydrogels using a dendritic monomer
      obtained from Behera's amine. The swelling and rheological performance, the non
      toxicity over fibroblast cells and the drug encapsulation capacity of the novel
      hydrogels suggests that the new materials can achieve great potential as carrier
      for drug delivery and other potential biomedical applications.

PMID- 23553983
TI  - Photoactivation of (p-methoxyphenyl)(trifluoromethyl)diazirine in the presence of
      phenolic reaction partners.
AB  - Shine light on your chemistry! Irradiating 3-(4-methoxyphenyl)-3
      (trifluoromethyl)-3H-diazirine in the presence of equimolar solutions of phenol
      and tyrosine derivatives leads to Friedel-Crafts alkylations (see scheme), which
      suggests a strategy for the development of "cleaner" diazirines for chemical
      biology.

PMID- 23553985
TI  - Catalytic activity of Pt/TaB2(0001) for the oxygen reduction reaction.

PMID- 23553986
TI  - Species sensitivity distribution evaluation for chronic nickel toxicity to marine
      organisms.
AB  - In Europe, the European Union's Existing Substances Regulation (EEC 793/93), the
      REACH Regulation, and Water Framework Directive all share common guidance for
      conducting environmental effects assessments, which can be further used to derive
      predicted no effect concentrations (PNECs) and environmental quality standards
      (EQS) for chemical substances. To meet the criteria for using a species
      sensitivity distribution (SSD) in the effects assessment of Ni for marine
      organisms, chronic toxicity data from the published scientific literature were
      augmented with toxicity testing of several additional marine species including: a
      unicellular alga (Dunalliela tertiolecta), a diatom (Skeletonema costatum), 2
      macroalgae (Champia parvula, Macrocystis pyrifera), 2 mollusks (Crassostrea
      gigas, Mytilus galloprovincialis), 2 echinoderms (Dendraster excentricus,
      Strongylocentrotus purpuratus), a polychaete (Neanthes arenaceodentata), and a
      fish (Cyprinodon variegatus). Based on this updated database, which includes
      chronic Ni toxicity data for a total of 17 marine species, HC5 values (hazardous
      concentrations to 5% of the species) were derived using an SSD. The most
      sensitive species is a tropical sea urchin from the Caribbean region, Diadema
      antillarum, which has an EC10 that is approximately 6-fold less than the EC10 for
      the second most sensitive species tested. There is some uncertainty in the
      representativeness of D. antillarum to temperate European marine waters because
      1) a European sea urchin species (Paracentrotus lividus) is approximately 48-fold
      less sensitive to Ni, and (2) ambient marine Ni concentrations in at least some
      European waters closely approach the D. antillarum EC10. The HC5 values with and
      without D. antillarum included in the SSD are 3.9 and 20.9 MUg/L, respectively.
      Site-specific toxicity testing with local species may be warranted for locations
      where Ni concentrations fall between the range in HC5s of 3.9 to 20.9 MUg/L.

PMID- 23553987
TI  - Haemostatic role of intermediate filaments in adhered platelets: importance of
      the membranous system stability.
AB  - The role of platelets in coagulation and the haemostatic process was initially
      suggested two centuries ago, and under appropriate physiological stimuli, these
      undergo abrupt morphological changes, attaching and spreading on damaged
      endothelium, preventing bleeding. During the adhesion process, platelet
      cytoskeleton reorganizes generating compartments in which actin filaments,
      microtubules, and associated proteins are arranged in characteristic patterns
      mediating crucial events, such as centralization of their organelles, secretion
      of granule contents, aggregation with one another to form a haemostatic plug, and
      retraction of these aggregates. However, the role of Intermediate filaments
      during the platelet adhesion process has not been explored. J. Cell. Biochem.
      114: 2050-2060, 2013. (c) 2013 Wiley Periodicals, Inc. 

PMID- 23553988
TI  - A simple and rapid single kernel screening method to estimate amylose content in
      rice grains.
AB  - INTRODUCTION: In rice breeding programmes large number of grain samples are
      routinely analysed for amylose content (AC) through a tedious spectrophotometric
      method that also involves high reagent costs. OBJECTIVE: Here, we propose a rapid
      and economic screening technique for assessment of AC based on the amylose-iodine
      complex formation in the cut grains of rice, which we refer to as the cut grain
      dip (CGD) method. METHODS: The CGD method involves cutting the rice kernels in
      the middle with a pair of scissors and dipping the cut end in an optimised
      iodide:iodine (KI-I) solution termed the rapid amylose detection solution (RADS).
      RESULTS: It was found that the time taken for deep blue colouration by the cut
      end of the grains after dipping in RADS was proportional to the AC. The CGD
      method was further validated in a large set of rice mutants with varied AC.
      CONCLUSION: The proposed method can be used to screen samples for AC rapidly,
      with a single rice caryopsis, without any costly equipment and can be especially
      suitable for screening of mutants and segregants with altered AC in large
      breeding populations.

PMID- 23553989
TI  - Cu-catalyzed chemoselective preparation of 2-(pinacolato)boron-substituted
      allylcopper complexes and their in situ site-, diastereo-, and enantioselective
      additions to aldehydes and ketones.

PMID- 23553990
TI  - MiR-23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth
      in gastric cancer cells.
AB  - Copy number variation (CNV) and abnormal expression of microRNAs (miRNAs) always
      lead to deregulation of genes in cancer, including gastric cancer (GC). However,
      little is known about how CNVs affect the expression of miRNAs. By integrating
      CNV and miRNA profiles in the same samples, we identified eight miRNAs (miR
      1274a, miR-196b, miR-4298, miR-181c, miR-181d, miR-23a, miR-27a and miR-24-2)
      that were located in the amplified regions and were upregulated in GC. In
      particular, amplification of miR-23a-27a-24-2 cluster and miR-181c-181d cluster
      frequently occurred at 19p13.13 and were confirmed by genomic real-time PCR in
      another 25 paired GC samples. Moreover, in situ hybridization (ISH) experiments
      represented that mature miR-23a was increased in GCs (75.5%, 40/53) compared with
      matched normal tissues (28.6%, 14/49, P = 0.001). Knocking down of miR-23a
      expression inhibited BGC823 cell growth in vitro and in vivo. In addition, the
      potential target genes of miR-23a were investigated by integration of mRNA
      profile and miRNA TargetScan predictions, we found that upregulation of miR-23a
      and downregulation of metallothionein 2A (MT2A) were detected simultaneously in
      70% (7/10) of the miRNA and mRNA profiles. Furthermore, an inverse correlation
      between miR-23a and MT2A expression was detected in GCs and normal tissues.
      Through combining luciferase assay, we confirmed that MT2A is a potential target
      of miR-23a. In conclusion, these results suggest that integration of CNV-miRNA
      mRNA profiling is a powerful tool for identifying molecular signatures, and that
      miR-23a might play a role in regulating MT2A expression in GC.

PMID- 23553991
TI  - Multicenter measurements of myelin water fraction and geometric mean T2 : intra-
      and intersite reproducibility.
AB  - PURPOSE: To assess the reproducibility of myelin water fraction (MWF) and
      geometric mean T2 (GMT2 ), which are in vivo markers of pathological changes
      underlying disability and progression in diseases such as multiple sclerosis.
      MATERIALS AND METHODS: Five healthy volunteers were scanned twice within 24 hours
      at six different sites using the same manufacturer's 3T magnetic resonance (MR)
      system. T2 distributions were produced by fitting multiecho 3D T2 data using non
      negative least squares, with stimulated echo correction. MWF, the fraction of
      signal with T2 between 15 and 40 msec to the entire signal, and GMT2 , the mean
      T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white
      matter. RESULTS: Intrasite coefficients of variation (COVs) were low (mean 3.99%
      for MWF and 0.51% for GMT2 ), as were intersite COVs (mean 4.68% for MWF, 0.31%
      for GMT2 ). Scan-rescan intraclass correlation coefficients (ICCs) (0.76 for MWF
      and 0.93 for GMT2 ) and Bland-Altman plots indicated good agreement between
      single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for
      GMT2 ), revealing good intersite reliability. CONCLUSION: MWF and GMT2 measures
      are reproducible between scans and across sites with an equivalent MR scanner and
      sequence protocol. Multicenter clinical trials using quantitative T2 relaxation
      are feasible.

PMID- 23553992
TI  - The role of vitamin D in improving physical performance in the elderly.
AB  - There is an ongoing debate over the role of serum 25(OH) vitamin D [25(OH)D]
      levels in maintaining or improving physical performance and muscle strength. Much
      of the controversy is because of the variability between studies in participants'
      characteristics, baseline serum 25(OH)D levels, and baseline physical
      functioning. The aim of this ancillary study conducted within a randomized
      controlled clinical trial was to investigate whether supplementation with 400 or
      2000 IU vitamin D3 daily for 6 months would improve measures of physical
      performance and muscle strength in a community-dwelling elderly population aged
      65 to 95 years. Those with the slowest gait speed improved their ability to do
      chair-stand tests after vitamin D supplementation. This finding remained
      significant after controlling for potential confounding variables. There was also
      an inverse correlation between serum 25(OH)D levels and fat mass index (FMI)
      among women, suggesting that higher supplementation with vitamin D is needed as
      weight increases. The results of this study suggest that supplementation with
      vitamin D may be most beneficial in older populations who have low baseline
      physical functioning.

PMID- 23553993
TI  - Inflammation-induced hyperalgesia and spinal microglia reactivity in neonatal
      rats.
AB  - BACKGROUND: Peripheral inflammation and nerve injury evoke pain behaviours in
      adult rodents mediated by sensitization, a process that involves the activation
      of microglia in the spinal cord. In neonates, however, peripheral inflammation,
      but not nerve injury, induces a lasting hyperalgesia. It is known that microglia
      does not activate after nerve injury in young pups; however, changes in microglia
      associated with inflammation in neonatal animals have not been studied. METHODS:
      Inflammation was induced by unilateral intraplantar injection of carrageenan,
      complete Freund's adjuvant or zymosan in 10-day-old rats. Rats were tested for
      mechanical sensitivity in response to punctuate stimulation of the dorsal surface
      of the hind paw using calibrated von Frey filaments. Immunohistochemistry was
      used to detect changes in size and density of microglial cells using the specific
      marker Iba-1. The effects of minocycline applications (120 MUg, i.t.) on spinal
      microglia and behaviour induced by zymosan inflammation were studied. RESULTS:
      Hind paw inflammation in young P10 rats, with either of the agents used, produced
      an immediate hyperalgesia, which lasted more than 7 days. A concomitant and
      significant increase in cell size and density in Iba-1-positive cells was
      observed in the spinal dorsal horn. These morphological changes in spinal
      microglia were observed as early as 1-h post-inflammation. Intrathecal and
      systemic administration of minocycline blocked the hyperalgesia and the changes
      in spinal microglia produced by zymosan. CONCLUSIONS: Results suggest a key role
      for spinal microglia activation in the development of hyperalgesia following
      inflammation in neonatal animals.

PMID- 23553994
TI  - Gabriel Falloppius (1523-1562) and the facial canal.
AB  - Gabriel Falloppius is known for his contributions to anatomy. Indeed, many
      anatomic structures bear his name, such as the Fallopian tubes, and his
      descriptions often contradicted those of other notable anatomists, such as Galen
      and Andreas Vesalius. In his textbook "Observationes Anatomicae," he described
      for the first time the structures of the ear, eye, and female reproductive
      organs, and elucidated the development of the teeth. Furthermore, Falloppius
      described the facial canal. The objectives of this paper are to provide an
      overview of Falloppius's life and to discuss the clinical relevance of the facial
      canal as understood from his description of this anatomic structure.

PMID- 23553995
TI  - Statistical reporting deficiencies in environmental toxicology.
AB  - Null hypothesis significance testing is one of the most widely used forms of
      statistical testing in environmental toxicology. In this short communication, the
      authors show that the reporting of statistical information when using null
      hypothesis significance testing is frequently inadequate in environmental
      toxicology research. The authors demonstrate this by analyzing the statistical
      information reported for papers employing t tests or analyses of variance in the
      Environmental Toxicology section of Environmental Toxicology and Chemistry in
      2010, which comprised 68% of papers published by this journal in that year. Of
      these papers, 60% fail to report exact p values, 85% fail to provide degrees of
      freedom, and 90% fail to report critical effect sizes. Statistical power was
      reported in only <2% of the published papers. The insufficient provision of
      statistical information makes interpretation of study results by reviewers and
      readers difficult. Consistently reporting exact p values with degrees of freedom,
      considering and explicitly stating biologically relevant critical effect sizes,
      and reporting statistical power associated with nonsignificant results would be
      easy to implement and would promote scientific progress in environmental
      toxicology through increased statistical transparency.

PMID- 23553996
TI  - Characterization of internal pudendal artery atherosclerosis using aortography
      and multi-detector computed angiography.
AB  - OBJECTIVE: To compare multi-detector computed tomography (MDCT) and aortography
      in the assessment of the internal pudendal artery (IPA) anatomy and degree of
      atherosclerosis. METHODS: Eighty-three patients underwent MDCT and aortography of
      the pelvic vasculature prior to consideration for transcatheter aortic valve
      replacement. These modalities were used to localize the IPA origin, degree of
      stenosis (normal: <50% stenosis or abnormal: >50% stenosis or occlusion), normal=
      and extent of calcification, quantified using a nominal scale (0 = no
      calcification, 1 = <25%, 2 = 25-50%, 3 = >50% of the IPA length). These studies
      were read independently and were blinded. RESULTS: Mean patient age was 78 +/- 8
      years with a high prevalence of atherosclerotic disease (70% coronary artery
      disease (CAD) and 30% peripheral artery disease (PAD)). The prevalence of having
      IPA stenosis or occlusion was 54%, 18% had an accessory arterial origin. In a
      patient-based analysis, the sensitivity of MDCT for detecting significant
      proximal IPA disease was 100% and, specificity 74%, positive predictive valve was
      66%, and negative predictive value was 100%. In assessing the distal IPA and
      cavernosal arteries, the sensitivity was 100%, specificity was 64%, positive
      predictive value 89%, and negative predictive value of 100%. MDCT used
      significantly more contrast and more radiation than aortography. CONCLUSION: MDCT
      had a high false-positive rate and low false-negative rate in evaluating the
      proximal IPA. For the distal IPA or cavernosal arteries, MDCT showed a high
      sensitivity and low specificity. These modalities have complementary roles in the
      assessment of IPA patency.

PMID- 23553997
TI  - Impact of Phytolacca americana extracts on gene expression of colon cancer cells.
AB  - Native Americans have used Phytolacca americana to treat breast ailments,
      gastrointestinal disorders, rashes, and inflammation. Some anti-cancer and anti
      viral research has been reported on this perennial herb, but none has been
      published concerning the effects of its extracts on cancer cell genes. In this
      study, changes in gene expression at the transcription level were evaluated in
      HCT-116 colon cancer cells after exposure to P. americana ethanol extract and its
      water fraction using the Human Cancer Pathway Finder PCR Array. Of the genes
      significantly affected in HCT-116 cells exposed to the ethanol extract at 3200
      ug/ml, changes in expression of MYC, PLAU, and TEK may benefit the treatment of
      colon cancer. Exposing the cells to 1600 ug/ml of the water fraction resulted in
      several gene changes that may also be beneficial in the treatment of colon
      cancer: NME4, TEK, and THBS1. A few genes on this array that are known to play a
      specific role in colon cancer had activities changed in a way that may be
      detrimental in the treatment of colon cancer. Further studies should be performed
      to understand how these changes would impact colon cancer treatment.

PMID- 23553998
TI  - Borylated arylisoquinolines: photophysical properties and switching behavior of
      promising tunable fluorophores.
AB  - A series of nine borylated arylisoquinolines has been prepared with systematic
      variation in their electronic properties and their photophysical properties were
      investigated. The color of their fluorescence can be finely tuned by changing the
      properties of the aryl moiety, which is involved in internal-charge-transfer
      processes. For example, methoxy-substituted compound 5 showed an intense green
      emission, whereas dimethylamino-substituted compound 6 showed an orange-red
      emission. These new fluorophores were tested for their potential as molecular
      switches with external ionic stimuli, such as protons and fluoride ions. On the
      one hand, protonation of the isoquinoline moiety led to fluorescence enhancement
      for compounds that showed weak charge transfer and fluorescence quenching for
      compounds that showed strong charge transfer. On the other hand, the formation of
      ate complexes with fluoride led to strong fluorescence quenching in all of the
      investigated cases.

PMID- 23553999
TI  - The impact of penicillin skin testing on clinical practice and antimicrobial
      stewardship.
AB  - BACKGROUND: Penicillin skin testing (PST) is a simple and reliable way of
      diagnosing penicillin allergy. After being off the market for 4 years,
      penicilloyl-polylysine was reintroduced in 2009 as PRE-PEN. We describe the
      negative predictive value (NPV) of PST and the impact on antibiotic selection in
      a sample of hospitalized patients with a reported history of penicillin allergy.
      METHODS: We introduced a quality improvement process at our 861-bed tertiary care
      hospital that used PST to guide antibiotic usage in patients with a history
      consistent with an immunoglobulin E (IgE)-mediated reaction to penicillin.
      Subjects with a negative PST were then transitioned to a beta-lactam agent for
      the remainder of their therapy. NPV of skin testing was established at 24-hour
      follow-up. We are reporting the result of 146 patients tested between March 2012
      and July 2012. RESULTS: A total of 146 patients with a history of penicillin
      allergy and negative PST were treated with beta-lactam antibiotics. Of these,
      only 1 subject experienced an allergic reaction to the PST. The remaining 145
      patients tolerated a full course of beta-lactam therapy without an allergic
      response, giving the PST a 100% NPV. We estimated that PST-guided antibiotic
      alteration for these patients resulted in an estimated annual savings of $82,000.
      CONCLUSION: Patients with a history of penicillin allergy who have a negative PST
      result are at a low risk of developing an immediate-type hypersensitivity
      reaction to beta-lactam antibiotics. The increased use of PST may help improve
      antibiotic stewardship in the hospital setting.

PMID- 23554000
TI  - A novel WT1 mutation in familial wilms tumor.

PMID- 23554001
TI  - Development of aquatic toxicity benchmarks for oil products using species
      sensitivity distributions.
AB  - Determining the sensitivity of a diversity of species to spilled oil and
      chemically dispersed oil continues to be a significant challenge in spill
      response and impact assessment. We used standardized tests from the literature to
      develop species sensitivity distributions (SSDs) of acute aquatic toxicity values
      for several petroleum products and 2 Corexit oil dispersants. Fifth percentile
      hazard concentrations (HC5s) were computed from the SSDs and used to assess
      relative oil product toxicity and in evaluating the feasibility of establishing
      toxicity benchmarks for a community of species. The sensitivity of mysids
      (Americamysis bahia) and silversides (Menidia beryllina) were evaluated within
      the SSDs to determine if these common test species were appropriate surrogates
      for a broader range of species. In general, SSD development was limited by the
      availability of acute toxicity values that met standardization criteria for a
      diversity of species. Pooled SSDs were also developed for crude oil and Corexit
      dispersants because there was only small variability in the HC5s among the
      individual oil or dispersant products. The sensitivity of mysids and silversides
      varied across the oil and dispersant products, with the majority of toxicity
      values greater than the HC5. Application of SSDs appears to be a reasonable
      approach to developing oil product toxicity benchmarks, but additional toxicity
      data are needed for a larger range of species conducted under standardized test
      conditions.

PMID- 23554002
TI  - Scoping review of the literature on shoulder impairments and disability after
      neck dissection.
AB  - BACKGROUND: The purpose of this article was to provide a review of the literature
      on shoulder disability after neck dissection. METHODS: A literature review was
      performed using Ovid Medline and Embase databases. A total of 306 abstracts and
      78 full-text articles were reviewed. Forty-two articles were eligible for
      inclusion. RESULTS: Patients undergoing nerve-sacrifice neck dissections have
      greater disability and lower quality of life scores than those undergoing neck
      dissections with the least manipulation (ie, selective neck dissections).
      Shoulder impairments can still occur in patients undergoing selective neck
      dissections. Disability typically improves over time in patients undergoing nerve
      sparing neck dissections. CONCLUSION: There was significant variability in the
      literature in terms of the prevalence and recovery of shoulder morbidity after
      neck dissection. This variability may not just be related to surgical technique
      or rehabilitation, but also to study design, definitions, and the variability in
      disability questionnaires used.

PMID- 23554003
TI  - The relationship between balance control and vitamin D in Parkinson's disease-a
      pilot study.
AB  - BACKGROUND: Balance problems and falls are a major source of morbidity and
      mortality in patients with Parkinson's disease. Vitamin D supplementation reduces
      falls and sway in neurologically intact elderly fallers, but effects in
      Parkinson's disease are not established. METHODS: To study this relationship and
      select outcome measures for a vitamin D intervention study, balance function and
      vitamin D concentration were quantified in a series of Parkinson's patients in a
      cross-sectional, observational study. Participants underwent a battery of 5
      balance tests. RESULTS: Serum vitamin D concentrations were correlated inversely
      with Parkinson's severity, as measured by the motor Unified Parkinson's Disease
      Rating Scale. Among the balance measures, vitamin D concentrations were
      correlated with automatic posture responses to backwards translation,
      specifically with response strength and stance weight asymmetry. CONCLUSIONS:
      These findings support the hypothesis that vitamin D plays a role in balance
      among patients with Parkinson's disease and identify specific outcome measures
      for detecting effects of vitamin D upon balance.

PMID- 23554004
TI  - Suicide and anxiety in DSM-5.

PMID- 23554005
TI  - Within-lesion differences in quantitative MRI parameters predict contrast
      enhancement in multiple sclerosis.
AB  - PURPOSE: To investigate the relationship between quantitative magnetic resonance
      imaging (qMRI) and contrast enhancement in multiple sclerosis (MS) lesions. We
      compared maps of T1 relaxation time, proton density (PD), and magnetization
      transfer ratio (MTR) between lesions with and without contrast enhancement as
      quantified by the amount of T1 shortening postcontrast agent (CA). MATERIALS AND
      METHODS: In 17 patients with relapsing-remitting MS (RRMS), 15 with progressive
      MS (PMS), and 17 healthy controls, T1, PD, and MTR were measured at 3T and T1
      mapping was repeated after CA administration. Manually drawn MS-lesions (3D
      FLAIR) were labeled as enhancing if post-CA T1-shortening exceeded mean T1
      shortening in normal-appearing white matter (NAWM) by at least 2 standard
      deviations. Precontrast T1, PD, and MTR were compared in enhancing lesions,
      nonenhancing lesions, NAWM, and gray matter. RESULTS: Precontrast T1, PD, and MTR
      differed significantly between enhancing and nonenhancing lesions in RRMS and PMS
      patients (all P < 0.01). In PMS patients, PD of NAWM, enhancing, and nonenhancing
      lesions and MTR and T1 of gray matter differed significantly from RRMS and
      controls. Only MTR of gray matter differed between RRMS and controls. CONCLUSION:
      Contrast enhancement in MS quantified by relative T1 shortening may be predicted
      by precontrast abnormalities of T1, PD, and MTR and likely represents blood-brain
      barrier damage.

PMID- 23554006
TI  - Role of melatonin receptor MT(2) and quinone reductase II in the regulation of
      the redox status of 3T3-L1 preadipocytes in vitro.
AB  - We have examined the role of melatonin receptor MT2 and quinone reductase II in
      the regulation of the redox status of preadipocytes (3T3-L1) in vitro. 3T3-L1
      cells were treated with melatonin at a physiological concentration (10(-9) mol/L)
      and a supraphysiological (pharmacological) concentration (10(-3) mol/L) for 24 h.
      Luzindole (10(-4) mol/L), an antagonist of MT2 receptor, and prazosin (10(-5)
      mol/L), an inhibitor of quinone reductase II, were added 30 min before subsequent
      exposure of the cells to melatonin. The level of oxidative stress was determined
      by the analysis of activities of enzymes neutralising reactive oxygen species,
      and determination of the malondialdehyde (MDA) content. Melatonin increased
      activities of manganese and copper-zinc superoxide dismutase (MnSOD, Cu/ZnSOD)
      and catalase (CAT) at both a physiological concentration (10(-9) mol/L) and a
      pharmacological concentration (10(-3) mol/L). MDA content was unchanged, whereas
      activities of glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rd)
      were increased only by the physiological concentration. Both effects were
      partially inhibited by luzindole, but not prazosin. These observations suggest
      that melatonin, acting at least partially via MT2 receptors, can increase
      antioxidant enzymes activities in 3T3-L1 preadipocytes.

PMID- 23554007
TI  - A tryptophanyl-tRNA synthetase/tRNA pair for unnatural amino acid mutagenesis in
      E. coli.

PMID- 23554008
TI  - Probing lung microstructure with hyperpolarized noble gas diffusion MRI:
      theoretical models and experimental results.
AB  - The introduction of hyperpolarized gases ((3)He and (129)Xe) has opened the door
      to applications for which gaseous agents are uniquely suited-lung MRI. One of the
      pulmonary applications, diffusion MRI, relies on measuring Brownian motion of
      inhaled hyperpolarized gas atoms diffusing in lung airspaces. In this article we
      provide an overview of the theoretical ideas behind hyperpolarized gas diffusion
      MRI and the results obtained over the decade-long research. We describe a simple
      technique based on measuring gas apparent diffusion coefficient (ADC) and an
      advanced technique, in vivo lung morphometry, that quantifies lung microstructure
      both in terms of Weibel parameters (acinar airways radii and alveolar depth) and
      standard metrics (mean linear intercept, surface-to-volume ratio, and alveolar
      density) that are widely used by lung researchers but were previously available
      only from invasive lung biopsy. This technique has the ability to provide unique
      three-dimensional tomographic information on lung microstructure from a less than
      15 s MRI scan with results that are in good agreement with direct histological
      measurements. These safe and sensitive diffusion measurements improve our
      understanding of lung structure and functioning in health and disease, providing
      a platform for monitoring the efficacy of therapeutic interventions in clinical
      trials.

PMID- 23554010
TI  - New approaches to functionalizing metal-coordinated N2.

PMID- 23554009
TI  - Modeling the microstructurally dependent mechanical properties of poly(ester
      urethane-urea)s.
AB  - Poly(ester-urethane-urea) (PEUU) is one of many synthetic biodegradable
      elastomers under scrutiny for biomedical and soft tissue applications. The goal
      of this study was to investigate the effect of the experimental parameters on
      mechanical properties of PEUUs following exposure to different degrading
      environments, similar to that of the human body, using linear regression,
      producing one predictive model. The model utilizes two independent variables of
      poly(caprolactone) (PCL) type and copolymer crystallinity to predict the
      dependent variable of maximum tangential modulus (MTM). Results indicate that
      comparisons between PCLs at different degradation states are statistically
      different (p < 0.0003), while the difference between experimental and predicted
      average MTM is statistically negligible (p < 0.02). The linear correlation
      between experimental and predicted MTM values is R(2) = 0.75.

PMID- 23554011
TI  - Ellagic acid induces apoptosis in TSGH8301 human bladder cancer cells through the
      endoplasmic reticulum stress- and mitochondria-dependent signaling pathways.
AB  - To investigate the effects of ellagic acid on the growth inhibition of TSGH8301
      human bladder cancer cells in vitro, cells were incubated with various doses of
      ellagic acid for different time periods. The phase-contrast microscope was used
      for examining and photographing the morphological changes in TSGH8301 cells. Flow
      cytometric assay was used to measure the percentage of viable cells, cell cycle
      distribution, apoptotic cells, ROS, mitochondrial membrane potential (DeltaPsim),
      Ca(2+) , caspase-9 and -3 activities in TSGH8301 cells after exposure to ellagic
      acid. Western blotting was used to examine the changes of cell cycle and
      apoptosis associated proteins levels. Results indicated that ellagic acid induced
      morphological changes, decreased the percentage of viable cells through the
      induction of G0/G1 phase arrest and apoptosis, and also showed that ellagic acid
      promoted ROS and Ca(2+) productions and decreased the level of DeltaPsim and
      promoted activities of caspase-9 and -3. The induction of apoptosis also
      confirmed by annexin V staining, comet assay, DAPI staining and DNA gel
      electrophoresis showed that ellagic acid induced apoptosis and DNA damage in
      TSGH8301 cells. Western blotting assay showed that ellagic acid promoted p21, p53
      and decreased CDC2 and WEE1 for leading to G0/G1 phase arrest and promoting BAD
      expression, AIF and Endo G, cytochrome c, caspase-9 and -3 for leading to
      apoptosis in TSGH8301 cells. On the basis of these observations, we suggest that
      ellagic acid induced cytotoxic effects for causing a decrease in the percentage
      of viable cells via G0/G1 phase arrest and induction of apoptosis in TSGH8301
      cells.

PMID- 23554012
TI  - Using the kingfisher (Alcedo atthis) as a bioindicator of PCBs and PBDEs in the
      dinghushan biosphere reserve, China.
AB  - The Dinghushan Biosphere Reserve is a nature reserve and a site for the study of
      tropical and subtropical forest ecosystems. Rapid industrialization and intensive
      electronic waste-recycling activities around the biosphere reserve have resulted
      in elevated levels of industrial organic contaminants in the local environment
      that may cause adverse effects on wildlife that inhabits this area. In the
      present study, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
      (PBDEs), and 2 alternative brominated flame retardants (BFRs)-decabromodiphenyl
      ethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE)-were
      investigated in the biosphere reserve and a reference site by using the
      kingfisher (Alcedo atthis) as a bioindicator. Residue concentrations in
      kingfishers from the Dinghushan Biosphere Reserve ranged from 490 ng/g to 3000
      ng/g, 51 ng/g to 420 ng/g, 0.44 ng/g to 90 ng/g, and 0.04 ng/g to 0.87 ng/g lipid
      weight for ?PCBs, ?PBDEs, DBDPE, and BTBPE, respectively. With the exception of
      the BTBPE, these levels were 2 to 5 times higher than those detected in
      kingfishers from the reference site. The contaminant patterns from the biosphere
      reserve were also different, with larger PCB contributions in comparison with the
      reference site. The estimated predator-prey biomagnification factors (BMFs)
      showed that most of the PCB and PBDE congeners and BTBPE were biomagnified in
      kingfishers from the biosphere reserve. The calculated toxic equivalent quantity
      (TEQ) concentrations of major coplanar PCB congeners in kingfishers from the
      biosphere reserve ranged from 18 pg/g to 66 pg/g wet weight, with some of these
      TEQ concentrations reaching or exceeding the levels known to impair bird
      reproduction and survival.

PMID- 23554013
TI  - Transcatheter aortic valve implantation without balloon predilation: a single
      center pilot experience.
AB  - AIM: To assess the results of transcatheter aortic valve implantation (TAVI)
      using the Medtronic CoreValve prosthesis (Medtronic, Minneapolis, MN), without
      balloon predilation, in high-risk patients with degenerated severe aortic
      stenosis. METHODS AND RESULTS: Fifty-one consecutive patients who underwent
      direct TAVI, 98% through a transfemoral approach. Patients were 79 +/- 8 years of
      age, 74% in New York Heart Association classes III or IV and at high risk for
      surgical valve replacement (mean logistic EuroScore 20 +/- 15). Mean aortic valve
      area was 0.7 +/- 0.2 cm(2). Procedural success rate was 94.2%. In-hospital, there
      were 2 deaths, 1 minor stroke with minimal sequelae, and 14 (28%) pacemaker
      implantation. At 30 days, there was one additional stroke and no new deaths. The
      mean postprocedural transprosthetic gradient was 15 +/- 5 mm Hg; periprosthetic
      severe regurgitation was absent and moderate in one case. After a median follow
      up of 7 months, there were five additional deaths (two cardiac), while 84% of
      survivors were in New York Heart Association classes I or II. CONCLUSIONS: These
      results suggest that direct CoreValve implantation in patients with severe aortic
      stenosis is feasible and may lead to hemodynamic and clinical improvement in
      patients who are poor candidates for aortic valve surgery, pending confirmation
      in larger series with longer follow-up.

PMID- 23554014
TI  - Atypical depressive symptoms and obesity in a national sample of older adults
      with major depressive disorder.
AB  - BACKGROUND: The objectives of this study are to present findings on the rate of
      obesity associated with classic, atypical, and undifferentiated depression by
      comparing with those without depression in a nationally representative sample of
      United States older adults. METHODS: The authors used data from the 2001 to 2002
      National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), which
      included 10,557 adults 60 years of age and older. Chi-square tests were used to
      compare classic, atypical, and undifferentiated as well as nondepressed control
      in sociodemographic characteristics. Then, logistic regressions adjusting for
      sociodemographic characteristics were used to evaluate associations of rate of
      current obesity (defined as Body Mass Index (BMI) > 30) across the three
      depressive groups (classic, atypical, and undifferentiated depression) and
      nondepressed control. Lifetime, current, and past depression were examined.
      RESULTS: Significant differences were found between atypical and classic
      depression in sex, age, marital status, race, and personal income. After
      adjusting for sex, age, marital status, race, and personal income, the rate of
      obesity was significantly greater for respondents with atypical depression than
      respondents with classic, undifferentiated depression, or without depression.
      Same results were found in lifetime, current, and past depression. CONCLUSION:
      Our findings suggest that the heterogeneity of depression should be considered
      when examining the effect of depression on obesity in old age. Prevention
      measures should be designed and delivered to older adults with atypical
      depression.

PMID- 23554015
TI  - Fluorescence and phosphorescence of single C60 molecules as stimulated by a
      scanning tunneling microscope.

PMID- 23554016
TI  - Impact of hospitalist communication-skills training on patient-satisfaction
      scores.
AB  - BACKGROUND: Hospital patient-satisfaction scores now affect hospital payment, but
      little research addresses how hospitals or clinicians might improve performance.
      OBJECTIVE: To assess the impact of a communication-skills training program on
      patient satisfaction with doctor communication and overall hospital care. DESIGN:
      Preintervention vs postintervention comparison of patient-satisfaction scores. We
      designed a communication-skills training program for hospitalists consisting of
      three 90-minute sessions, based on a popular framework. SETTING: Nonteaching
      hospitalist service in an urban academic hospital. MEASUREMENTS: Doctor
      communication items from the Hospital Consumer Assessment of Healthcare Providers
      and Systems (HCAHPS) and Press Ganey surveys, and HCAHPS overall hospital rating.
      RESULTS: Overall, 61 (97%) of 63 hospitalists completed the first session, 44
      (70%) completed the second session, and 25 (40%) completed the third session of
      the program. Patient-satisfaction data was available for 278 patients during the
      preintervention period and 186 patients during the postintervention period. Two
      of the 3 HCAHPS and all 5 of the Press Ganey doctor-communication items were
      rated higher during the postintervention period, but no result was statistically
      significant. Similarly, the overall hospital rating was higher during the
      postintervention period, but the result was not significant. Analyses based on
      level of hospitalist participation did not show significant differences.
      CONCLUSIONS: Patient satisfaction did not significantly improve after a
      communication-skills training program for hospitalists. Because of the small
      sample size, larger studies are needed to assess whether such a program might
      truly improve patient satisfaction.

PMID- 23554017
TI  - Synergistic effects of ultrashort wave and bone marrow stromal cells on nerve
      regeneration with acellular nerve allografts.
AB  - Acellular nerve allografts (ANA) possess bioactivity and neurite promoting
      factors in nerve tissue engineering. Previously we reported that low dose
      ultrashort wave (USW) radiation could enhance the rate and quality of peripheral
      nerve regeneration with ANA repairing sciatic nerve defects. Meanwhile, ANA
      implanted with bone marrow stromal cells (BMSCs) exhibited a similar result.
      Thus, it is interesting to know whether it might yield a synergistic effect when
      USW radiation is combined with BMSCs-laden ANA. Here we investigated the
      effectiveness of ANA seeded with BMSCs, combined with USW therapy on repairing
      peripheral nerve injuries. Adult male Wistar rats were randomly divided into four
      groups: Dulbecco's modified Eagle's medium (DMEM) control group, BMSCs-laden
      group, ultrashort wave (USW) group and BMSC + USW group. The regenerated nerves
      were assayed morphologically and functionally, and growth-promoting factors in
      the regenerated tissues following USW administration or BMSCs integration were
      also detected. The results indicated that the combination therapy caused much
      better beneficial effects evidenced by increased myelinated nerve fiber number,
      myelin sheath thickness, axon diameter, sciatic function index, nerve conduction
      velocity, and restoration rate of tibialis anterior wet weight. Moreover, the
      mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial
      growth factor (VEGF) in the spinal cord and muscles were elevated significantly.
      In conclusion, we found a synergistic effect of USW radiation and BMSCs treatment
      on peripheral nerve regeneration, which may help establish novel strategies for
      repairing peripheral nerve defects.

PMID- 23554018
TI  - Storage of magnetization as singlet order by optimal control designed pulses.
AB  - PURPOSE: The use of hyperpolarization to enhance the sensitivity of MRI has so
      far been limited by the decay of the polarization through T1 relaxation.
      Recently, methods have been proposed that extend the lifetime of the
      hyperpolarization by storing the spin order in slowly relaxing singlet states.
      METHODS: With this aim, optimal control theory was applied to create pulses that
      for near-equivalent spins accomplish transfers in and out of the singlet state
      with maximum efficiency while ensuring robustness toward variations in the
      nuclear spin system Hamiltonian (chemical shift, J-couplings, B1 and B0 magnetic
      field inhomogeneity). RESULTS: The pulses are designed to accomplish efficient
      transfer with low B1 amplitude, essential for applications on preclinical and
      clinical MR scanners. CONCLUSION: It is demonstrated that significantly improved
      efficiency and robustness can be obtained within the limitations of typical MR
      scanner performance.

PMID- 23554019
TI  - Thoracic aortic aneurysm in infancy in aneurysms-osteoarthritis syndrome due to a
      novel SMAD3 mutation: further delineation of the phenotype.
AB  - Recently, mutations in the SMAD3 gene were found to cause a new autosomal
      dominant aneurysm condition similar to Loeys-Dietz syndrome (LDS), mostly with
      osteoarthritis, called aneurysms-osteoarthritis syndrome (AOS). Our 3-year-old
      propositus underwent correction of an inguinal hernia at 3 months and
      substitution of the ascending aorta for pathologic dilation at 12 months of age.
      Family history reveals aortic dilation in his mother at 30 years, death due to
      aortic dissection of an 18-year-old maternal aunt, surgical replacement of the
      ascending aorta because of aneurysm in a maternal uncle at 19 years, postpartum
      death of the maternal grandmother at 24 years and surgical intervention because
      of thoracic aortic aneurysm in a brother of the propositus' grandmother at 54
      years. The affected individuals present with several other signs of connective
      tissue disease, but the two adult patients evaluated revealed no radiologic
      evidence of osteoarthritis. Molecular testing of the TGFBR1 and TGFBR2 genes,
      involved in LDS, resulted negative, but analysis of SMAD3 disclosed the novel
      heterozygous loss-of-function mutation c.1170_1179del (p.Ser391AlafsX7) in exon 9
      in all affected family members, confirming the diagnosis of AOS. SMAD3 mutations
      should be considered in patients of all ages with LDS-like phenotypes and
      negative TGFBR1/2 molecular tests, especially in the presence of aortic root or
      ascending aortic aneurysms, even though signs of early onset osteoarthritis are
      absent.

PMID- 23554020
TI  - Synthesis of autophagosomal marker protein LC3-II under detergent-free
      conditions.

PMID- 23554022
TI  - Thoughts on feto-maternal tolerance: is there a lesson to be learned from
      allogeneic haematopoietic stem cell transplantation?

PMID- 23554021
TI  - Micro(RNA)managing endoplasmic reticulum stress.
AB  - Cellular disturbances that cause accumulation of misfolded proteins in the
      endoplasmic reticulum (ER) lead to a condition referred to as "ER stress" and
      trigger the unfolded protein response (UPR), a signaling pathway that attempts to
      restore ER homeostasis. The complexity of UPR signaling can generate adaptive and
      apoptotic outputs, depending on the nature and duration of the ER stress.
      MicroRNAs (miRNAs), small non-coding RNAs that typically repress gene expression,
      have recently emerged as key gene regulators of the proadaptive/proapoptotic
      molecular switch emanating from the ER. Importantly, select miRNAs have been
      shown to directly regulate key UPR components.

PMID- 23554023
TI  - Transoral robotic surgery for the management of oropharyngeal minor salivary
      gland tumors.
AB  - BACKGROUND: In this study we report our preliminary experience with the use of
      transoral robotic surgery (TORS) for the management of minor salivary gland
      malignancies of the oropharynx and outcomes. METHODS: This was a retrospective
      review of 10 patients followed over a 5-year period at a single tertiary academic
      medical center. Patient, tumor, clinicopathologic, functional, and oncologic
      outcomes were collected and analyzed. RESULTS: All cancers treated were either T1
      (40%) or T2 (60%). Negative margins were achieved in all patients. Four patients
      received adjuvant radiation therapy (40%). No patients experienced surgical
      complications and all had excellent functional outcomes. Mean follow-up was 24
      months (range, 2-60 months) with locoregional and distant control achieved in 8
      patients (80%) and 9 patients (90%), respectively. CONCLUSIONS: Minor salivary
      malignancies of the oropharynx are a surgical disease. Short-term follow-up data
      demonstrate feasibility, low morbidity, good functional, and oncologic results
      for TORS management of these malignancies.

PMID- 23554024
TI  - Redefining the coccygeal plexus.
AB  - The coccygeal plexus is variably described in anatomy texts and has rarely been
      studied despite the idiopathic nature of coccydynia in up to one-third of
      affected patients. The plexus was therefore investigated using a combination of
      microdissection and histology. The distal sacrum and coccyx in continuity with
      ischiococcygeus were removed en bloc from 16 embalmed cadavers (mean age 78 +/-
      10 years, 7 females) with no local disease. Ten specimens underwent
      microdissection of the coccygeal plexus and the remaining six were examined
      histologically after staining with hematoxylin and eosin and S100
      immunohistochemistry to demonstrate nerve fibers. The coccygeal plexus is formed
      within ischiococcygeus from the ventral rami of S4, S5, and Co1 with a
      contribution (gray rami communicantes) from the sacral sympathetic trunk. It
      gives rise to anococcygeal nerves which pierce ischiococcygeus and the
      sacrospinous ligament to supply the subcutaneous tissue on the dorsal aspect of
      the coccyx. Some branches from the plexus pass medially anterior to the coccyx.
      The coccycgeal plexus is formed within ischiococcygeus rather than on its pelvic
      surface and appears to supply skin in the anococcygeal region. It probably also
      contributes to the innervation of ischiococcygeus, the sacrospinous ligament,
      coccygeal ligaments, and periosteum. It deserves to be considered as a potential
      pain generator that may be implicated in some patients with coccydynia.

PMID- 23554025
TI  - Cross-linking density and temperature effects on the self-assembly of SiO2
      PNIPAAm core-shell particles at interfaces.
AB  - SiO2-PNIPAAm core-shell microgels (PNIPAAm=poly(N-isopropylacrylamide)) with
      various internal cross-linking densities and different degrees of polymerization
      were prepared in order to investigate the effects of stability, packing, and
      temperature responsiveness at polar-apolar interfaces. The effects were
      investigated using interfacial tensiometry, and the particles were visualized by
      cryo-scanning electron microscopy (SEM) and scanning force microscopy (SFM). The
      core-shell particles display different interfacial behaviors depending on the
      polymer shell thickness and degree of internal cross-linking. A thicker polymer
      shell and reduced internal cross-linking density are more favorable for the
      stabilization and packing of the particles at oil-water (o/w) interfaces. This
      was shown qualitatively by SFM of deposited, stabilized emulsion droplets and
      quantitatively by SFM of particles adsorbed onto a hydrophobic planar silicon
      dioxide surface, which acted as a model interface system. The temperature
      responsiveness, which also influences particle-interface interactions, was
      investigated by dynamic temperature protocols with varied heating rates. These
      measurements not only showed that the particles had an unusual but very regular
      and reversible interface stabilization behavior, but also made it possible to
      assess the nonlinear response of PNIPAAm microgels to external thermal stimuli.

PMID- 23554026
TI  - In vivo identification of sentinel lymph nodes using MRI and size-controlled and
      monodispersed magnetite nanoparticles.
AB  - PURPOSE: To develop a sentinel lymph node (SN) identification method using
      accurately synthesized magnetic nanoparticles (MNPs), as an enhanced specific SN
      tracer in combination with magnetic resonance imaging (MRI) in intact rodent and
      SN metastasis models. MATERIALS AND METHODS: Three sizes of MNPs were originally
      synthesized. We developed an experimental rat SN model, with brachial lymph nodes
      (Br) as the SN and the axillary lymph node (Ax) as the second lymph node, and
      injection of MNPs via the front paw. SN detectability was evaluated in vivo using
      T1 -weighted MR images after injection of the synthesized MNPs, and the amount of
      iron in the Br and in the Ax was assessed using inductively coupled plasma
      optical emission spectrometry. RESULTS: The highest ratios of the amount of iron
      in the Br versus the Ax were 3.1 and 3.3, using 20-nm MNPs after 2- and 24-hour
      injections. The appropriate dose and particle diameter for MRI detection was
      optimized, and the SN was optimally distinguished in the normal and metastatic
      rat models using MRI after a 0.4 mg/kg 20-nm MNP injection. CONCLUSION: We
      developed and optimized a useful SN identification method using MRI in rodent
      models.

PMID- 23554027
TI  - Pathological gambling in Parkinson's disease: subthalamic oscillations during
      economics decisions.
AB  - Pathological gambling develops in up to 8% of patients with Parkinson's disease.
      Although the pathophysiology of gambling remains unclear, several findings argue
      for a dysfunction in the basal ganglia circuits. To clarify the role of the
      subthalamic nucleus in pathological gambling, we studied its activity during
      economics decisions. We analyzed local field potentials recorded from deep brain
      stimulation electrodes in the subthalamic nucleus while parkinsonian patients
      with (n = 8) and without (n = 9) pathological gambling engaged in an economics
      decision-making task comprising conflictual trials (involving possible risk
      taking) and non conflictual trials. In all parkinsonian patients, subthalamic low
      frequencies (2-12 Hz) increased during economics decisions. Whereas, in patients
      without gambling, low-frequency oscillations exhibited a similar pattern during
      conflictual and non conflictual stimuli, in those with gambling, low-frequency
      activity increased significantly more during conflictual than during non
      conflictual stimuli. The specific low-frequency oscillatory pattern recorded in
      patients with Parkinson's disease who gamble could reflect a subthalamic
      dysfunction that makes their decisional threshold highly sensitive to risky
      options. When parkinsonian patients process stimuli related to an economics task,
      low-frequency subthalamic activity increases. This task-related change suggests
      that the cognitive-affective system that drives economics decisional processes
      includes the subthalamic nucleus. The specific subthalamic neuronal activity
      during conflictual decisions in patients with pathological gambling supports the
      idea that the subthalamic nucleus is involved in behavioral strategies and in the
      pathophysiology of gambling.

PMID- 23554028
TI  - Cocoa powder triggers neuroprotective and preventive effects in a human
      Alzheimer's disease model by modulating BDNF signaling pathway.
AB  - The molecular mechanisms linking Abeta to the onset of neurotoxicity are still
      largely unknown, but several lines of evidence point to reactive oxygen species,
      which are produced even under the effect of nanomolar concentrations of soluble
      Abeta-oligomers. The consequent oxidative stress is considered as the mediator of
      a cascade of degenerative events in many neurological disorders. Epidemiological
      studies indicate that dietary habits and antioxidants from diet can influence the
      incidence of neurodegenerative disorders such as Alzheimer's and Parkinson's
      diseases. In the recent years, a number of reviews have reported on
      neuroprotective effects of polyphenols in cell and animal models. However, the
      majority of these studies have focused only on the anti-oxidant properties of
      these compounds and less on the mechanism/s of action at cellular level. In this
      work we investigated the effect of cocoa polyphenolic extract on a human AD in
      vitro model. The results obtained, other than confirming the anti-oxidant
      properties of cocoa, demonstrate that cocoa polyphenols triggers neuroprotection
      by activating BDNF survival pathway, both on Abeta plaque treated cells and on
      Abeta oligomers treated cells, resulting in the counteraction of neurite
      dystrophy. On the light of the results obtained the use of cocoa powder as
      preventive agent for neurodegeneration is further supported.

PMID- 23554029
TI  - Clinical study to assess the efficacy and safety of a citrus polyphenolic extract
      of red orange, grapefruit, and orange (Sinetrol-XPur) on weight management and
      metabolic parameters in healthy overweight individuals.
AB  - The present study investigated the efficacy and safety effects of Sinetrol-XPur
      (polyphenolic citrus dry extract) in weight management; metabolic parameters; and
      inflammatory, glycemic and oxidative status. In a 12-week, randomized, double
      blind, placebo-controlled trial, Sinetrol-XPur was given to overweight subjects
      twice daily with meals in the tested group (N = 47) versus a placebo group (N =
      48). Waist and hip circumference and abdominal fat were decreased in the Sinetrol
      XPur group as compared with the placebo group (p < 0.0001) (-5.71% vs. -1.56% for
      waist, -4.71% vs. -1.35% for hip and -9.73% vs. -3.18% for fat). Inflammatory
      markers were reduced (C-reactive protein: -22.87% vs. +61%; fibrinogen: -19.93%
      vs. -1.61%, p < 0.01). Oxidative stress was lowered as seen by the reduction of
      malondialdehyde (-14.03% vs. 2.76%) and the increase in superoxide dismutase and
      glutathione (17.38% vs. 2.19% and 4.63% vs. -2.36%, respectively, p < 0.01). No
      adverse effects were observed. Kidney, liver, and lipid panels remained
      unchanged. These results indicated that Sinetrol-XPur supplementation is a viable
      option for reducing abdominal fat, waist and hip circumference, and body weight
      and for improving inflammatory, glycemic, and oxidative status in healthy
      overweight individuals.

PMID- 23554031
TI  - Is there a cure for systemic lupus erythematosus?
AB  - The morbidity and mortality of systemic lupus erythematosus (SLE) is a subject of
      intense relevance in the literature, yet descriptions of prolonged and sustained
      remissions or even cure are barely reported. In recent decades the life
      expectancy in SLE patients has improved, but the quality of life seems to be poor
      compared with other chronic diseases and with the general population. The
      immunopathogenesis of SLE is complex and not fully understood, so patients have
      been treated with nonspecific immunosuppressive therapies. But in recent years,
      because of advances in basic science, targeted therapies have been developed.
      Despite the progress made in treating SLE, currently a cure in SLE seems to be a
      myth. SLE it seems, remains incurable. A specific treatment has not emerged to
      directly abrogate a disease-specific autoimmune response. Relapsing
      manifestations and complications of treatment still remain important markers of
      morbidity.

PMID- 23554030
TI  - A pediatric phase 1 trial of vorinostat and temozolomide in relapsed or
      refractory primary brain or spinal cord tumors: a Children's Oncology Group phase
      1 consortium study.
AB  - PURPOSE: We conducted a pediatric phase I study to estimate the maximum tolerated
      dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetic properties of
      vorinostat, a histone deacetylase (HDAC) inhibitor, when given in combination
      with temozolomide in children with refractory or recurrent CNS malignancies.
      PATIENTS AND METHODS: Vorinostat, followed by temozolomide approximately 1 hour
      later, was orally administered, once daily, for 5 consecutive days every 28 days
      at three dose levels using the rolling six design. Studies of histone
      accumulation in peripheral blood mononuclear cells were performed on Day 1 at 0,
      6, and 24 hours after vorinostat dosing. Vorinostat pharmacokinetics (PK) and
      serum MGMT promoter status were also assessed. RESULTS: Nineteen eligible
      patients were enrolled and 18 patients were evaluable for toxicity. There were no
      DLTs observed at dose level 1 or 2. DLTs occurred in four patients at dose level
      3: thrombocytopenia (4), neutropenia (3), and leucopenia (1). Non-dose limiting
      grade 3 or 4 toxicities related to protocol therapy were also hematologic and
      included neutropenia, lymphopenia, thrombocytopenia, anemia, and leucopenia.
      Three patients exhibited stable disease and one patient had a partial response.
      There was no clear relationship between vorinostat dosage and drug exposure over
      the dose range studied. Accumulation of acetylated H3 histone in PBMC was
      observed after administration of vorinostat. CONCLUSION: Five-day cycles of
      vorinostat in combination with temozolomide are well tolerated in children with
      recurrent CNS malignancies with myelosuppression as the DLT. The recommended
      phase II combination doses are vorinostat, 300 mg/m(2) /day and temozolomide, 150
      mg/m(2) /day.

PMID- 23554032
TI  - Spanish LupusPRO: cross-cultural validation study for lupus.
AB  - PURPOSE: LupusPRO is a disease-targeted, patient-reported, outcome measure that
      was developed and validated among US patients with systemic lupus erythematosus
      (SLE). To expand the availability and use of the tool, we undertook a cross
      cultural adaptation and validation study of the Spanish-translated version of the
      LupusPRO. METHOD: Forward and back translations of the 43-item English LupusPRO
      were undertaken and pretested in five individuals. The finalized Spanish version
      was administered to 211 SLE patients of Hispanic ancestry from the US and Latin
      America. Short Form-36 (Spanish) and Spanish LupusPRO were also administered.
      Disease activity was ascertained using the systemic lupus erythematosus disease
      activity index. A Spanish LupusPRO questionnaire that could be completed within 2
      3 days was mailed to SLE patients of Hispanic ancestry and they mailed it back.
      Internal consistency reliability, test-retest reliability, criterion validity
      (against disease activity or health status) and convergent validity were tested.
      All reported p values are two-tailed. RESULTS: A total of 211 Spanish-speaking
      SLE patients (90% women) participated. Test-retest reliability of LupusPRO
      domains ranged from 0.80-0.95, while internal consistency reliability of the
      domains ranged from 0.71-0.96. Convergent validity with corresponding domains of
      the SF-36 was present. All health-related quality of life domains of the LupusPRO
      (except procreation) performed well against disease activity measures,
      establishing its criterion validity. Confirmatory factor analysis showed a good
      fit. CONCLUSION: The Spanish LupusPRO has fair psychometric properties and is now
      available to be included in clinical trials and in longitudinal studies for
      testing of responsiveness to change.

PMID- 23554033
TI  - ADAMTS-13 metalloprotease abnormalities in systemic lupus erythematosus: is there
      a correlation with disease status?
AB  - To clarify the role of ADAMTS-13 in the pathogenesis of thrombotic
      microangiopathy in systemic lupus erythematosus (SLE) we evaluated ADAMTS-13
      profile (metalloprotease antigen levels, anti-ADAMTS-13 autoantibody levels,
      activity) in distinct patient groups according to disease activity, extent of
      cumulative tissue damage and history of antiphospholipid syndrome or end-organ
      damage. Forty-one lupus patients were analysed. ADAMTS-13 metalloprotease antigen
      levels and anti-ADAMTS-13 autoantibodies were evaluated by ELISA. ADAMTS-13
      activity was measured by Fluorescence resonance energy transfer (FRET) technique.
      ADAMTS-13 metalloprotease antigen levels were significantly decreased in patients
      with Systemic Lupus International Collaborative Clinics/American College of
      Rheumatology (SLICC/ACR) >1 (p<0.05). ADAMTS-13 metalloprotease antigen levels
      also exhibited a significant inverse correlation with anti-dsDNA levels (r= 
      0.60, p<0.05). Anti-ADAMTS-13 autoantibodies were marginally higher in patients
      with positive anti-dsDNA (p=0.08). Additionally, patients with positive anti
      ADAMTS-13 autoantibodies exhibited the lowest activity levels (p<0.05). To our
      knowledge ADAMTS-13 profile in SLE has not been studied in regard to composite
      structured indices. The results of this study suggest that in patients with
      active SLE or considerable cumulative tissue damage, ADAMTS-13 levels may be
      decreased and anti-ADAMTS-13 autoantibodies may partially mediate this reduction.
      Further evaluation of ADAMTS-13 profile may explain its role in the pathogenesis
      of thrombotic microangiopathy in lupus patients and reveal a potential prognostic
      marker of microthrombotic manifestations in SLE.

PMID- 23554034
TI  - Clinical characteristics and risk factors of intracranial hemorrhage in systemic
      lupus erythematosus.
AB  - We enrolled and reviewed 26 medical records of systemic lupus erythematosus (SLE)
      with intracranial hemorrhage (cases) and 104 randomly matched records of SLE
      without intracranial hemorrhage (controls) out of 6653 admitted patients at
      Peking Union Medical College Hospital from 1994 to 2012, to analyze the clinical
      characteristics and risk factors of intracranial hemorrhage in SLE. The incidence
      of SLE with intracranial hemorrhage was only 0.39% within the last 18 years at
      Peking Union Medical College Hospital. However, the in-hospital fatality rate was
      quite high (23.1%). Headache was the most common symptom (53.5%) in SLE patients
      with intracranial hemorrhage. The anatomical localization of the hemorrhages in
      the brain was predominantly located in the cerebrum. Intracranial hemorrhage
      could happen in either stable or active SLE patients. SLE patients with
      intracranial hemorrhage presented other neuropsychiatric syndromes defined by the
      American College of Rheumatology (ACR) in 1999, thrombocytopenia and
      antiphospholipid syndrome more frequently than controls. Thrombocytopenia was the
      independent risk factor for intracranial hemorrhage coexisting with SLE
      (OR=3.687, 95% CI 1.510-9.001, p=0.004).

PMID- 23554035
TI  - Effects of tetra-arsenic tetra-sulfide on BXSB lupus-prone mice: a pilot study.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology
      that affects multiple tissues and organs. Arsenic trioxide (ATO) has been used in
      lupus-prone mice with a regulatory effect on immune abnormality. Tetra-arsenic
      tetra-sulfide (As4S4), a traditional Chinese medicine, is effective on acute
      promyelocytic leukemia with mild side effects than ATO. In this study, a pilot
      study was performed to investigate the effects and the mechanism of As4S4 on the
      lupus-prone BXSB mice. Improvement of monocytosis (p<0.05) in spleen and
      decreased serum interleukin-6 (IL-6) (p=0.0277) were observed with As4S4
      treatment. As4S4-treated mice exhibited amelioration of skin, liver and renal
      disease with mild side effects. Histological analysis revealed that As4S4
      suppressed immune complex deposition, mesangial proliferation and inflammatory
      cell infiltration in kidney and liver. Our study support that As4S4 selectively
      suppresses cutaneous lupus and nephritis in BXSB mice and might be a potential
      treatment for SLE.

PMID- 23554036
TI  - Autoantibodies to the functionally active RING-domain of Ro52/SSA are associated
      with disease activity in patients with lupus.
AB  - The Ro52 protein of the Ro/SSA antigen was recently defined as an E3 ligase
      controlling cytokine production. Autoantibodies from systemic lupus erythematosus
      (SLE) patients targeting the Ro52-RING domain, containing the E3 ligase activity,
      have been shown to inhibit the E3 ligase activity of Ro52. The objective of the
      present study was to investigate correlations between clinical parameters in
      patients with SLE and levels of Ro/SSA (Ro52 and Ro60) and La/SSB autoantibodies,
      including autoantibodies directed towards the functional RING and B-box domains
      of the Ro52 protein. SLE patients (n=232) were clinically examined and disease
      activity indices collected concurrently to blood sampling. The samples were
      analyzed for immunological parameters including autoantibodies. Ro52 autoantibody
      levels were associated with more variables than the other analyzed antibodies and
      were significantly associated with several individual items related to sSS and
      the diagnosis of sSS itself (p=0.004). Other associated variables were high
      sedimentation rate (p=0.0003), levels of immunoglobulins (p=0.0003), and an
      inverse correlation with levels of lymphocytes (p=0.003) and leukocytes (p=0.01).
      Antibodies to the RING domain of Ro52, which is the functionally active domain
      with E3 ligase activity, were significantly correlated with disease activity as
      measured by the SLAM score. We conclude that autoantibodies against Ro52 and in
      particular its functional RING domain are important in lupus patients and
      associated with several clinical and laboratory features of the disease. The
      impact on disease activity of Ro52-RING specific antibodies was especially noted,
      and could imply a functional role for these autoantibodies in inhibiting Ro52
      activity, which is important for the control of proinflammatory cytokine
      production, including type 1 interferons.

PMID- 23554037
TI  - Urinary neutrophil gelatinase-associated lipocalin as a marker of severe lupus
      nephritis in children.
AB  - INTRODUCTION: More than 60% of children with systemic lupus erythematosus (SLE)
      develop lupus nephritis (LN). Neutrophil gelatinase-associated lipocalin (NGAL)
      is a protein secreted by leukocytes during inflammation and is overexpressed in
      the kidneys following ischemic and nephrotoxic damage. AIM: To study urinary and
      serum NGAL in children with SLE and investigate their possible role as markers of
      renal involvement. Methods Urinary and serum levels of NGAL were assessed in 33
      children with active SLE (22 with and 11 without LN) and compared to 15 matched
      controls. RESULTS: Children with SLE had elevated urinary NGAL as compared to
      controls (P<0.001). Levels of urinary NGAL were higher in patients with LN than
      those without LN (P<0.001). In patients with LN, serum levels of NGAL were not
      significantly different from controls (P=0.4) and urinary NGAL correlated with
      the renal score of the Systemic Lupus Erythematosus Disease Activity Index
      (r=0.5, P=0.02) but not with serum NGAL (P=0.5). Urinary NGAL was significantly
      predictive of class III and IV LN (P=0.005) with 91% sensitivity and 70%
      specificity to levels >= 10.07 ng/mg creatinine. Conclusions Urinary NGAL is a
      sensitive marker of proliferative nephritis in juvenile SLE.

PMID- 23554038
TI  - Association of a single nucleotide polymorphism in the SH2D1A intronic region
      with systemic lupus erythematosus.
AB  - SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated
      protein (SAP), is an adaptor protein. Recently, it was reported that SAP
      deficient mice were protected from systemic lupus erythematosus (SLE). In this
      study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE
      and analyzed its association with SLE. A case-control association study was
      conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506
      Japanese female SLE patients and 330 healthy female controls. The luciferase
      assay was performed to determine the functional role of the SNP associated with
      SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110,
      odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant
      model). The association of rs2049995 seemed to be stronger in the subset with the
      age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional
      evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold
      for the susceptible allele compared with the resistant allele. An intronic SNP of
      SH2D1A is associated with SLE.

PMID- 23554039
TI  - Kidney-limited thrombotic microangiopathy in patients with SLE treated with
      romiplostim.
AB  - We present the case of a 19 year-old Caucasian female with history of systemic
      lupus erythematosus (SLE) and normal baseline kidney function who developed
      severe acute renal failure following treatment of thrombocytopenia with the
      thrombopoietic agent romiplostim. Percutaneous kidney biopsy revealed thrombotic
      microangiopathy (TMA) without immune complex lupus glomerulonephritis. We discuss
      pathogenesis and differential diagnosis of TMA in patients with SLE and raise
      concerns regarding the use of thrombopoietic agents in such patients. Based on
      favorable long-term outcome in our case aggressive treatment and in particular
      prolonged use of plasma exchange in these patients are advocated.

PMID- 23554040
TI  - Infliximab-induced discoid lupus erythematosus.
AB  - Anti-tumor necrosis factor-alpha (TNF-alpha) immunotherapy is currently used in
      the treatment of various inflammatory diseases such as rheumatoid arthritis,
      psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease.
      Infliximab is a chimeric monoclonal antibody that binds to transmembrane-bound
      and soluble TNF-alpha. Previously, a discoid lupus erythematosus-like eruption
      linked to its use was rarely reported in patients with rheumatoid arthritis. We
      present a case of rheumatoid arthritis which developed such an eruption after
      treatment with infliximab. The lesions resolved after the discontinuation of
      infliximab. In the present case, the clinical, serological and
      immunohistochemical features of our patient are discussed with the literature.

PMID- 23554041
TI  - Metabolic syndrome in Chinese patients with systemic lupus erythematosus: no
      association with plasma cortisol level.
AB  - Our objective was to determine metabolic syndrome (MS) prevalence in Chinese
      patients with systemic lupus erythematosus (SLE) and to investigate the
      conditions that contribute to its development. 116 patients with SLE classified
      according to the American College of Rheumatology (ACR) classification criteria,
      and 115 controls were enrolled. MS was defined by the joint interim statement of
      the International Diabetes Federation Task Force on Epidemiology and Prevention;
      National Heart, Lung, and Blood Institute; American Heart Association; World
      Heart Federation; International Atherosclerosis Society; and International
      Association for the Study of Obesity (IDF/NHLBI/AHA/WHF/IAS/IASO). SLE features
      and treatment of SLE were assessed. Fasting insulin and cortisol levels of 30
      newly diagnosed, untreated patients and 33 age and sex-matched controls were
      detected. MS prevalence was 34.2% in patients with SLE and 14.8% in controls
      (p=0.002). Lupus patients with MS had less frequency of hydroxychloroquine (HCQ)
      intake (16.0% vs 45.8%; p=0.012). Untreated patients with SLE had higher levels
      of fasting insulin (10.92 +/- 13.53 vs 5.48 +/- 5.43 uU/mL, p<0.001) and plasma
      cortisol at 16:00 (257.22 +/- 177.98 vs 139.84 +/- 63.46 nmol/L, p=0.001), but
      lower plasma cortisol at 08:00 (195.51 +/- 149.84 vs 278.95 +/- 136.27 nmol/L,
      p=0.024). Comparisons regarding steroid therapy, levels of insulin and cortisol
      were not statistically significant between patients with MS and without MS. The
      Chinese patients with SLE presented a higher MS prevalence and fasting insulin
      than controls. MS was not associated with the steroid therapy and plasma
      cortisol. HCQ use proved to be protective against MS. The circadian rhythm of
      cortisol may differ in patients with SLE.

PMID- 23554042
TI  - Acute toxicity of pyraclostrobin and trifloxystrobin to Hyalella azteca.
AB  - Fungicide application rates on row crop agriculture have increased across the
      United States, and subsequently, contamination of adjacent wetlands can occur
      through spray drift or field runoff. To investigate fungicide toxicity, Hyalella
      azteca amphipods were exposed to 2 fungicide formulations, Headline and Stratego,
      and their active strobilurin ingredients, pyraclostrobin and trifloxystrobin.
      Water-only exposures resulted in similar median lethal concentration (LC50; 20-25
      ug/L) values for formulations and strobilurin ingredients, suggesting that
      toxicity is due to strobilurin ingredients. These values were below
      concentrations that could occur following spray drift over embedded cropland
      wetlands. When fungicides were added to overlying water of sediment-water
      microcosms, toxicity was reduced by 500% for Headline and 160% for Stratego,
      compared with water-only exposures, based on the total amount of fungicide added
      to the systems. In addition, when fungicides were added to sediment prior to the
      addition of water, the reduction in toxicity was even greater, with no toxicity
      occurring at environmentally relevant levels. Differences in toxicity among
      exposure groups were explained by dissipation from water as toxicity values based
      on measured water concentrations were within 20% between all systems. The present
      study reinforces previous studies that Headline and Stratego are toxic to
      nontarget aquatic organisms. However, the presence of sediment is likely to
      ameliorate some toxicity of fungicide formulations, especially if spraying occurs
      prior to wetland inundation.

PMID- 23554043
TI  - The osteogenic differentiation of mesenchymal stem cells by controlled cell-cell
      interaction on micropatterned surfaces.
AB  - Cell-cell interaction plays an important role in the control of cell functions.
      The precise control of cell-cell interaction will provide a useful tool to
      elucidate its influence on stem cell differentiation. In this study, four types
      of micropatterned surfaces were prepared by ultraviolet photolithography to
      investigate the effect of cell-cell interaction on the osteogenic differentiation
      of human mesenchymal stem cells (MSCs). Single MSCs adhered on the micropatterned
      surfaces following the micropatterns. Single cells on the isolated, barbell,
      linear, and honeycomb dot micropatterns had zero, one, two, and three cell-cell
      interaction partners, respectively. The number of cell-cell interaction of single
      MSCs was controlled by the different micropatterns, which showed evident effects
      on actin filament structure assembly and osteogenic differentiation of MSCs. MSCs
      with two and three interaction partners showed a significantly higher rate of
      osteogenic differentiation than did isolated single cells and cells with only one
      interaction partner. Thus, the osteogenic differentiation of MSCs was enhanced
      with increased cell-cell interaction. These results highlight the importance of
      cell-cell interaction in stem cell differentiation.

PMID- 23554044
TI  - Emergency and prophylactic use of miniaturized veno-arterial extracorporeal
      membrane oxygenation in transcatheter aortic valve implantation.
AB  - OBJECTIVES: To report our center's experience using veno-arterial extracorporeal
      membrane oxygenation (vaECMO) in transcatheter aortic valve implantation (TAVI).
      BACKGROUND: In TAVI, short-term mortality closely relates to life threatening
      procedural complications. VaECMO can be used to stabilize the patient in
      emergency situations. However, for the prophylactic use of vaECMO in very high
      risk patients undergoing TAVI there is no experience. METHODS: From January 2009
      to August 2011, we performed 131 TAVI. Emergency vaECMO was required in 8 cases
      (7%): ventricular perforation (n = 3), hemodynamic instability/cardiogenic shock
      (n = 4), hemodynamic deterioration due to ventricular tachycardia (n = 1). Since
      August 2011, during 83 procedures, prophylactic vaECMO was systematically used in
      very high-risk patients (n = 9, 11%) and emergency ECMO in one case (1%) due to
      ventricular perforation. RESULTS: Median logistic EuroScore in prophylactic
      vaECMO patients was considerably higher as compared to the remaining TAVI
      population (30% vs. 15%, P = 0.0003) while in patients with emergency vaECMO it
      was comparable (18% vs. 15%, P = 0.08). Comparing prophylactic to emergency
      vaECMO, procedural success and 30-day mortality were 100% vs. 44% (P = 0.03) and
      0% vs. 44% (P = 0.02), respectively. Major vascular complications and rate of
      life threatening bleeding did not differ between both groups (11% vs. 11%, P =
      0.99 and 11% vs. 33%, P = 0.3) and were not vaECMO-related. CONCLUSIONS: Life
      threatening complications during TAVI can be managed using emergency vaECMO but
      mortality remains high. The use of prophylactic vaECMO in very high-risk patients
      is safe and may be advocated in selected cases.

PMID- 23554045
TI  - Is there still a future for hydrogenated vegetable oils?

PMID- 23554046
TI  - Reconstruction of magnetic resonance imaging by three-dimensional dual-dictionary
      learning.
AB  - PURPOSE: To improve the magnetic resonance imaging (MRI) data acquisition speed
      while maintaining the reconstruction quality, a novel method is proposed for
      multislice MRI reconstruction from undersampled k-space data based on compressed
      sensing theory using dictionary learning. THEORY AND METHODS: There are two
      aspects to improve the reconstruction quality. One is that spatial correlation
      among slices is used by extending the atoms in dictionary learning from patches
      to blocks. The other is that the dictionary-learning scheme is used at two
      resolution levels; i.e., a low-resolution dictionary is used for sparse coding
      and a high-resolution dictionary is used for image updating. Numerical
      experiments are carried out on in vivo 3D MR images of brains and abdomens with a
      variety of undersampling schemes and ratios. RESULTS: The proposed method (dual
      DLMRI) achieves better reconstruction quality than conventional reconstruction
      methods, with the peak signal-to-noise ratio being 7 dB higher. The advantages of
      the dual dictionaries are obvious compared with the single dictionary. Parameter
      variations ranging from 50% to 200% only bias the image quality within 15% in
      terms of the peak signal-to-noise ratio. CONCLUSION: Dual-DLMRI effectively uses
      the a priori information in the dual-dictionary scheme and provides dramatically
      improved reconstruction quality.

PMID- 23554047
TI  - Mechanisms of mitochondrial translational regulation.
AB  - The mitochondrial oxidative phosphorylation system is formed by multimeric
      enzymes. In the yeast Saccharomyces cerevisiae, the bc1 complex, cytochrome c
      oxidase and the F1 FO ATP synthase contain subunits of dual genetic origin. It
      has been recently established that key subunits of these enzymes, translated on
      mitochondrial ribosomes, are the subjects of assembly-dependent translational
      regulation. This type of control of gene expression plays a pivotal role in
      optimizing the biogenesis of mitochondrial respiratory membranes by coordinating
      protein synthesis and complex assembly and by limiting the accumulation of
      potentially harmful assembly intermediates. Here, the author will discuss the
      mechanisms governing translational regulation in yeast mitochondria in the light
      of the most recent discoveries in the field.

PMID- 23554048
TI  - Visualization of ureters on standard gynecological transvaginal scan: a
      feasibility study.
AB  - OBJECTIVE: To investigate the feasibility of identifying pelvic segments of
      normal ureters and measuring their size on standard transvaginal ultrasound
      examination. METHODS: This was a prospective observational study from June to
      July 2012. All women in the study underwent a transvaginal ultrasound examination
      performed for various indications either by an expert or by an intermediate-level
      operator. A standardized assessment of the pelvic organs was performed, recording
      any congenital or acquired uterine pathology and ovarian abnormalities.
      Visualization of pelvic segments of both ureters was attempted in all cases. The
      success in finding the ureters, the time required to identify them and their
      dimensions at rest and while exhibiting peristalsis were all recorded. RESULTS: A
      total of 245 consecutive women were included in the study. In all women at least
      one ureter was successfully identified. Both ureters were seen in 227 women
      (92.7% (95% CI, 89.4-96.0%)). In 17 (6.9% (95% CI, 3.7-10.1%)) the left ureter
      was not seen and in one woman (0.4% (95% CI, 0.0-1.2%)) the right ureter could
      not be visualized (P < 0.001). There were no significant differences in the
      median time required to visualize the right and left ureters (9.0 (interquartile
      range (IQR), 6.0-14.0) s vs 8.0 (IQR, 6.0 -14.0) s, respectively; P = 0.9). The
      median diameter of the right ureter was 1.7 (IQR, 1.4-2.2) mm at rest and 2.9
      (IQR, 2.4-3.6) mm during peristalsis. The median diameter of the left ureter was
      1.9 (IQR, 1.6-2.3) mm at rest and 2.9 (IQR, 2.4-3.6) mm during peristalsis.
      CONCLUSION: Pelvic segments of normal ureters can be identified in most women on
      transvaginal ultrasound examination. Visualization of the ureters could be
      integrated into the routine pelvic ultrasound examination, particularly in women
      presenting with pelvic pain or in those with suspected pelvic endometriosis.

PMID- 23554049
TI  - Furanodiene presents synergistic anti-proliferative activity with paclitaxel via
      altering cell cycle and integrin signaling in 95-D lung cancer cells.
AB  - Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well
      known Chinese medicinal herb that presents anti-proliferative activities in
      several cancer cell lines. Recently, we found that the combined treatment of FUR
      with paclitaxel (TAX) showed synergetic anti-proliferative activities in 95-D
      lung cancer cells. Herein, we showed that FUR reduced the cell numbers
      distributed in mitosis phase induced by TAX while increased those in G1 phase.
      The protein levels of cyclin D1, cyclin B1, CDK6 and c-Myc were all down
      regulated in the group of combined treatment. The dramatically down-regulated
      expression of integrin beta4, focal adhesion kinase and paxillin might partially
      contribute to the synergic effect. Though FUR alone obviously induced endoplasmic
      reticulum stress, this signaling pathway may not contribute to the synergetic
      anti-proliferative effect as the protein expression of CHOP and BIP was similar
      in FUR alone and combined treatment group.

PMID- 23554050
TI  - RNAi-mediated MMP-9 silencing inhibits mouse melanoma cell invasion and migration
      in vitro and in vivo.
AB  - MMP-9 participates in tumour growth, invasion, metastasis and vascularisation.
      Thus, inhibition of MMP-9 may be involved in the process of tumourigenesis. We
      have investigated the effect of RNAi-mediated MMP-9 silencing on inhibiting
      invasion and migration of mouse melanoma cell B16. A specific and optimised siRNA
      vector was used to target MMP-9 mRNA synthesis in B16 cells. Changes of invasion
      and migration capability of B16 cell were examined after transfection at
      different time, and a footpad tumour model was performed to measure the effect of
      MMP-9 siRNA on melanoma tumourigenesis in vivo. In vitro, down-regulation of MMP
      9 expression significantly inhibited B16 cell invasion and migration. In vivo,
      intratumoural injection of plasmid DNA expressing MMP-9 siRNA every 3 days for
      three times remarkably inhibited melanoma growth and also suppressed tumour
      metastasis. The results indicate that RNA-mediated targeting of MMP-9 may have
      promising applications for the treatment of melanoma. 

PMID- 23554051
TI  - Nonviral gene transfer strategies to promote bone regeneration.
AB  - Despite the inherent ability of bone to regenerate itself, there are a number of
      clinical situations in which complete bone regeneration fails to occur. In view
      of shortcomings of conventional treatment, gene therapy may have a place in cases
      of critical-size bone loss that cannot be properly treated with current medical
      or surgical treatment. The purpose of this review is to provide an overview of
      gene therapy in general, nonviral techniques of gene transfer including physical
      and chemical methods, RNA-based therapy, therapeutic genes to be transferred for
      bone regeneration, route of application including ex vivo application, and direct
      gene therapy approaches to regenerate bone.

PMID- 23554053
TI  - Folate and health: present and future.

PMID- 23554052
TI  - The stress response resolution assay. II. Quantitative assessment of
      environmental agent/condition effects on cellular stress resolution outcomes in
      epithelium.
AB  - Cellular stress responses consist of a complex network of pathways and linked
      processes that, when perturbed, are postulated to have roles in the pathogenesis
      of various human diseases. To assess the impact of environmental insults upon
      this network, we developed a novel stress response resolution (SRR) assay for
      investigation of cellular stress resolution outcomes and the effects of
      environmental agents and conditions thereupon. SRR assay-based criteria
      identified three distinct groups of surviving cell clones, including those
      resembling parental cells, those showing Hprt/HPRT mutations, and a third type,
      "Phenotype-altered" clones, that occurred predominantly in cells pretreated with
      a chemical mutagen, was heterogeneous in nature, and expressed significant
      alterations in cell morphology and/or function compared with parental cells.
      Further evaluation of Phenotype-altered clones found evidence of various
      alterations that resembled epithelial-to-mesenchymal transition, phenotype
      switching, checkpoint dysfunction, senescence barrier bypass, and/or epigenetic
      reprogramming. Phenotype-altered clones were found to occur spontaneously in a
      cell line with a mutator phenotype, to represent the major surviving clone type
      in a variation of the SRR assay, and to be tumorigenic in nude mice. Assessment
      of SRR assay final results showed that pretreatment with a chemical mutagen
      induced significant changes in cellular stress response prosurvival capacity, in
      damage avoidance versus damage tolerance stress resolution outcomes, and in the
      damage burden in the final surviving cell populations. Taken together, these
      results support the conclusion that use of the SRR assay can provide novel
      insights into the role of environmental insults in the pathogenesis of cancer and
      other human diseases.

PMID- 23554054
TI  - The influence of folate supplementation on global gene expression in normal
      colonic mucosa of subjects with colorectal adenoma.
AB  - SCOPE: We determined whether short-term supplementation with a physiological dose
      of folate alters global gene expression in the normal colonic mucosa of subjects
      with colorectal adenoma. METHODS AND RESULTS: Fourteen subjects with adenoma,
      randomised to receive folic acid (400MUg/day, n = 6) or placebo (n = 8) for 10
      weeks, had blood samples and colonic tissue biopsies collected before and after
      the intervention. RNA extracted from colonic tissue samples was used to determine
      global gene expression in the colon using Affymetrix(r) Microarray GeneChips and
      real-time RT-PCR. Following intervention, 67 genes were upregulated and 13 genes
      were downregulated in the folic acid group, while 21 genes were upregulated and
      none were downregulated in the placebo group (p < 0.05, adjusted for multiple
      testing). Thirty-six genes were upregulated and 18 genes were downregulated in
      the folic acid group when compared with placebo, but none of these were
      statistically significant after adjustment for multiple testing. These genes are
      involved in multiple pathways, including cell cycle, signal transduction, cell
      differentiation, transport, cell division, cell motility, protein transport, and
      immune response. CONCLUSION: These results indicate that while folic acid can
      modify gene expression, it is difficult to separate its effects from the natural
      variability in gene expression in the colon.

PMID- 23554058
TI  - Papillary thyroid carcinoma nodal surgery directed by a preoperative radiographic
      map utilizing CT scan and ultrasound in all primary and reoperative patients.
AB  - BACKGROUND: To study the diagnostic accuracy of physical examination (PE),
      ultrasonography (US), contrastenhanced computed tomography (CT) and in
      preoperative detection of macroscopic nodal metastasis in primary/recurrent
      papillary thyroid carcinoma (PTC) patients to determine if the routine addition
      of CT would be beneficial in accurate preoperative lymph-node surgery planning.
      METHODS: In a tertiary center prospective study, 162 PTC patients underwent
      preoperative lymph-node evaluation by PE, US, and CT. Sensitivity, specificity,
      positive/negative predictive value (PPV/NPV) of each nodal detection technique
      were calculated in central/lateral cervical compartments. The gold standard for
      diagnostic-accuracy was surgical pathology. RESULTS: In patients undergoing
      primary (Group I)/revision (Group II) surgical treatment for PTC, combined US/CT
      yielded significantly higher sensitivity for macroscopic lymph-node detection in
      both lateral and central neck, most marked in Group I-central compartment.
      CONCLUSIONS: Combined preoperative US/CT provides reliable, objective,
      preoperative macroscopic nodal metastasis map to design rational nodal surgery in
      primary/revision PTC patients.

PMID- 23554059
TI  - Obesity and melanoma: exploring molecular links.
AB  - Obesity is now a major health problem due to its rapidly increasing incidence
      worldwide and severe consequences. Among many conditions associated with obesity
      are some cancers including melanoma. Both genetic defects and environmental risk
      factors are involved in the carcinogenesis of melanoma. Activation of multiple
      signal pathways such as the PI3K/Akt and MAPK pathways are necessary for the
      initiation of melanoma. Activation of the MAPK pathway as a result of activating
      mutations in BRAF is commonly seen in melanoma though it alone is not sufficient
      to cause malignant transformation of melanocytes. Obesity can result in the
      activation of many signal pathways including PI3K/Akt, MAPK, and STAT3. The
      activation of these pathways may have a synergistic effect with the genetic
      defects thereby increasing the incidence of melanoma.

PMID- 23554060
TI  - Elimination half-life as a metric for the bioaccumulation potential of chemicals
      in aquatic and terrestrial food chains.
AB  - The assessment of chemicals as bioaccumulative in the regulatory process makes
      use of the bioconcentration factor as a metric. However, this metric does not
      account for the dietary uptake route and therefore cannot be applied to
      terrestrial food chains. In recent years, the biomagnification factor (BMF) and
      the trophic magnification factor (TMF) have been suggested as standard metrics
      for bioaccumulation. For regulatory purposes, though, the BMF and the TMF also
      suffer from a number of shortcomings. They are not applicable to assess uptake
      routes other than the diet (e.g., dermal uptake, as is important for personal
      care products). When measured in the field, they depend largely on biological and
      ecological factors and less so on the chemical's properties, and they are
      difficult to normalize and standardize. In the present study, the authors suggest
      the elimination half-life (EL0.5 ) of a chemical as an alternative metric for
      bioaccumulation. The EL0.5 is equivalent to the depuration rate constant (k2 )
      that is measured in various bioaccumulation and bioconcentration tests. This
      metric can be applied to air- and water-breathing animals, and it is valuable for
      all uptake routes. It has a number of practical advantages over the BMF and the
      TMF. In combination with a standard uptake scenario, the EL0.5 can also be linked
      directly to a BMF threshold of unity. Thus, the EL0.5 as a bioaccumulation metric
      overcomes the shortcomings of the BMF and the TMF while still conserving the
      advantages of the latter metrics.

PMID- 23554061
TI  - Chemistry and biology of oligovalent beta-(1->2)-linked oligomannosides: new
      insights into carbohydrate-based adjuvants in immunotherapy.
AB  - A series of oligovalent carbohydrate assemblies (ranging from mono- to
      pentavalent), derived from three structurally different beta-linked or beta-(1
      >2)-linked mannosides, has been chemically synthesized, and the respective
      compounds have been biologically evaluated in order to investigate their
      immunostimulatory properties. The Crich methodology for beta-mannosylation was
      successfully utilized to introduce the beta-linkages, and a click chemistry
      protocol was utilized to generate the oligovalent derivatives. A convenient
      protecting group strategy involving the simultaneous use of both p-methoxybenzyl
      and benzylidene groups was employed, which allowed a simple and cost-effective
      global deprotection step. The immunomodulatory properties of the synthesized
      multivalent mannosides were evaluated by assessing cytokine production in human
      white blood cell cultures. The Th2-type cytokines interleukin-4 and interleukin-5
      (IL-4 and IL-5), the Th1 cytokine interferon-gamma (IFN-gamma), the Treg cytokine
      IL-10, and the pro-inflammatory cytokine tumor necrosis factor (TNF) were
      included in the screening. A single trivalent acetylated mannobiose derivative
      was identified as a potent inducer of Treg and Th1 immune response, resulting in
      strong IL-10 and moderate IFN-gamma productions dose-dependently, while inducing
      no Th2 cytokine response. The immunomodulatory properties of this trivalent
      mannoside were further studied in vitro in allergen (Bet v)-stimulated human
      peripheral blood mononuclear cell cultures of birch pollen allergic subjects.
      Stimulation with birch pollen induced strong IL-4 and IL-5 responses, which could
      be suppressed by the trivalent acetylated mannobiose derivative. The IL-10
      response was also suppressed, whereas the production of IFN-gamma was strongly
      enhanced. The results suggest that the identified lead compound has suppressive
      effects on the Th2-type allergic inflammatory response and shows potential as a
      possible lead adjuvant for the specific immunotherapy of allergies.

PMID- 23554062
TI  - Incomplete cre-mediated excision leads to phenotypic differences between Stra8
      iCre; Mov10l1(lox/lox) and Stra8-iCre; Mov10l1(lox/Delta) mice.
AB  - In the Cre-loxp system, expression level and activity of Cre recombinase in a Cre
      deleter line are critical because these determine not only the cell specificity
      of gene knockout (KO), but also the efficiency of Cre-mediated excision in a
      specific cell lineage. Although the spatiotemporal expression pattern of a Cre
      transgene is usually defined upon the generation of the mouse line, the Cre
      excision efficiency in a specific targeted cell lineage is rarely evaluated and
      often assumed to be 100%. Incomplete excision can lead to highly variable
      phenotypes owing to mosaicism (i.e., coexistence of cells with the flox or the
      recombined flox allele) and this problem has long been overlooked. Here, we
      report that Stra8-codon-improved Cre recombinase (iCre), a transgenic allele
      expressing iCre under the control of the male germ cell-specific Stra8 promoter,
      could efficiently delete one Mov10l1 flox allele in spermatogenic cells, whereas
      the excision was incomplete when two Mov10l1 flox alleles were present. The
      incomplete Cre-mediated excision led to a testicular phenotype that was much less
      severe than that in the true conditional KO (inactivation, 100%) mice. Our
      findings suggest that it is essential to determine the efficiency of Cre excision
      when Cre-loxp system is used for deleting genes in a specific cell lineage and
      the Cre; gene(lox) (/)(Delta) genotype should be used to evaluate phenotypes
      instead of Cre; gene(lox/lox) owing to the fact that the latter usually bears
      incomplete deletion of the flox allele(s).

PMID- 23554063
TI  - Advanced maternal age in polyploidy with concurrent aneuploidy.

PMID- 23554064
TI  - Unusual tilted carbene coordination in carbene complexes of gallium(I) and
      indium(I).

PMID- 23554065
TI  - A cadaveric study of the anatomical variation of the origins of the celiac trunk
      and the superior mesenteric artery: a role in median arcuate ligament syndrome?
AB  - Gray's Anatomy states, "the celiac trunk is the first anterior branch of the
      abdominal aorta and arises just below the aortic hiatus. The superior mesenteric
      artery originates from the aorta c1.0 cm below the celiac trunk." (Standring,
      2008a, Gray's Anatomy. 40th Ed. London: Churchill Livingstone Elsevier, p. 1073
      1074). During dissection classes with medical students we found this not to be
      the case. We have re-evaluated the anatomy of the origins of the celiac trunk
      (CT) and superior mesenteric artery (SMA) and the relationship of the CT to the
      median arcuate ligament (MAL) in 99 cadavers. We have found the external distance
      between the CT and SMA to range from 0 to 20 mm (mean 3.4 mm, SD 5.17 mm), with
      the two in direct apposition in 57.6% (n = 99) of cases: a higher figure than
      previously documented. However, the internal distance between the CT and SMA
      ranged from 10 to 30 mm (mean 18.9 mm, SD 4.09 mm). There was no distance
      measurable between the MAL and the CT in 88 cadavers (92.6%, n = 95) and, of
      these, 32 (33.7%) showed evidence of compression or kinking of the CT. We suspect
      that the MAL is responsible for the approximation of the CT to the SMA in these
      cadavers, and that the high incidence of kinking of the CT (33.7% of cases) may
      have implications with regard to its role in MAL syndrome.

PMID- 23554066
TI  - Small biparietal diameter in the first trimester and pregnancy outcome.

PMID- 23554067
TI  - Orthopedic bioactive implants: Hydrogel enrichment of macroporous titanium for
      the delivery of mesenchymal stem cells and strontium.
AB  - Insufficient implant stability is an important determinant in the failure of
      cementless prostheses. To improve osseointegration, we aim at generating a
      bioactive implant combining a macroporous titanium (TT) with a biocompatible
      hydrogel to encapsulate osteo-inductive factors and osteoprogenitor cells.
      Amidation and cross-linking degree of an amidated carboxymethylcellulose hydrogel
      (CMCA) were characterized by FT-IR spectrometry and mechanical testing. Bone
      marrow mesenchymal stem cells (BMSCs) from osteoarthritic patients were cultured
      on CMCA hydrogels, TT, and TT loaded with CMCA (TT + CMCA) with an optimized
      concentration of SrCl2 to evaluate cell viability and osteo-differentiation.
      Amidation and cross-linking degree were homogeneous among independent CMCA
      batches. SrCl2 at 5 MUg/mL significantly improved BMSCs osteo-differentiation
      increasing calcified matrix (P < 0.01), type I collagen expression (P < 0.05) and
      alkaline phosphatase activity. TT + CMCA samples better retained cells into the
      TT mesh, significantly improving cell seeding efficiency with respect to TT (P <
      0.05). BMSCs on TT + CMCA underwent a more efficient osteo-differentiation with
      higher alkaline phosphatase (P < 0.05) and calcium levels compared to cells on
      TT. Based on these in vitro results, we envision the association of TT with
      strontium-enriched CMCA and BMSCs as a promising strategy to generate bioactive
      implants promoting bone neoformation at the implant site.

PMID- 23554068
TI  - Percutaneous closure of tricuspid paravalvular leak.
AB  - While transcatheter closure of mitral and aortic paravalvular leaks has been well
      described, there are no prior reports of such procedures for prosthetic tricuspid
      valves. We describe our experience with percutaneous closure of a tricuspid
      paravalvular leak in a 34-year-old patient with a history of tricuspid atresia.
      He had previously undergone repair with placement of a right atrium-to-right
      ventricle conduit and most recently, placement of a bio-prosthetic tricuspid
      valve. He subsequently developed significant tricuspid paravalvular leak with
      symptoms of severe right heart failure. His clinical status was improved
      following successful transcatheter closure of the defect.

PMID- 23554069
TI  - Circadian events in human diseases and in cytochrome P450-related drug metabolism
      and therapy.
AB  - The biochemical basis of the mammalian circadian clock can be described by
      transcriptional-translational feedback loops with a period of about 24 h. Crucial
      endogenous factors are under circadian control (i.e., body temperature, blood
      pressure, hormone secretion and metabolite levels). Also, drug metabolism,
      including phases I-III and the drug-responsive nuclear receptors, is controlled
      by the clock. Disturbances in circadian rhythm in humans can lead to pathologies,
      which is exemplified by increased cancer risk in long-term shift workers. On the
      other hand, best tolerability of drugs with minimum side effects can be achieved
      if the timing of drug treatment is synchronized with the patients' individual
      clock. The aim of this review is to underline the importance of accepting the
      individuals' endogenous clock which can contribute to personalized, patient
      friendly optimization of drug therapies.

PMID- 23554070
TI  - Phase-labeled reference EPI for frequency-segmented inhomogeneity corrections
      (PREFICS).
AB  - PURPOSE: To develop a method to correct for geometric distortions in non
      Cartesian echo planar imaging using data acquired in a fast prescan. METHODS:
      Echo planar images were obtained using a non-Cartesian density weighted k-space
      trajectory. In contrast to linear Cartesian acquisition, distortions arising in
      non-Cartesian acquisitions can only be corrected using conjugate phase-based
      methods. Up to now these methods require a time consuming field map acquisition
      in undistorted coordinates. In this work, a phase-labeled reference EPI scan was
      performed in a very short time, yielding a displacement map in distorted
      coordinates. Subsequently, this map was applied to itself and thus transformed
      into undistorted coordinates. The echo planar images were then corrected with a
      frequency-segmented conjugate phase method. The results were compared with
      corrections based on a multi-echo reference field map acquired in undistorted
      coordinates. RESULTS: Uncorrected density weighted EPI exhibited geometric
      distortions and severe ringing artifacts. These distortions could be successfully
      corrected using the novel method. The quality was comparable to corrections based
      on the multi-echo reference field map. The novel method shortens the field map
      acquisition duration by a factor of 64. CONCLUSION: The method presented allows
      correcting non-Cartesian EPI from a reference scan consisting of only two phase
      labeled echo planar images.

PMID- 23554072
TI  - Study finds no association between autism and vaccination.

PMID- 23554071
TI  - A mineral extract from red algae ameliorates chronic spontaneous colitis in IL-10
      deficient mice in a mouse strain dependent manner.
AB  - Inflammatory bowel disease is an urgent public health problem with a high
      incidence in developed countries. Alterations of lifestyle or dietary
      interventions may attenuate the disease progression and increase the efficacy of
      current therapies. Here we tested the effect of chronic supplementation with a
      mineral extract from red marine algae - rich in calcium (34%), magnesium,
      phosphorus, selenium and other trace minerals - in a clinically relevant model of
      spontaneous enterocolitis, interleukin (IL)-10(-/-) mice. The mineral extract was
      administered in the drinking water of Il10(-/-) mice on C57BL/6 J and BALB/c
      strain backgrounds for 25 weeks commencing from 3 to 4 weeks of age. The mineral
      extract ameliorated the spontaneous development of colitis and severity of
      disease in Il10(-/-) mice on a C57BL/6 J background. Mineral extract-treated
      Il10(-/-) C57BL/6 J strain mice had significantly reduced mortality, circulating
      levels of serum Amyloid A and reduced colonic tissue damage. In contrast,
      comparable treatment of Il10(-/-) mice on a BALB/c background with the mineral
      extract did not alter the course of colitis. These data demonstrate that chronic
      supplementation with a natural mineral extract selectively ameliorates
      spontaneous mild-moderate colitis in Il10(-/-) mice on a C57BL/6 J, but does not
      attenuate more moderate-severe colitis in BALB/c strain animals.

PMID- 23554073
TI  - Experts are ignored in stem cell decision.

PMID- 23554074
TI  - Ambitious plan for "tobacco-free" Scotland by 2034.

PMID- 23554075
TI  - OECD finds some countries are too restrictive about sharing personal data.

PMID- 23554076
TI  - Court rules that exemption from smoking ban for small Dutch cafes is "unlawful".

PMID- 23554077
TI  - Interstitial engraftment of adipose-derived stem cells into an acellular dermal
      matrix results in improved inward angiogenesis and tissue incorporation.
AB  - Acellular dermal matrices (ADM) are commonly used in reconstructive procedures
      and rely on host cell invasion to become incorporated into host tissues. We
      investigated different approaches to adipose-derived stem cells (ASCs)
      engraftment into ADM to enhance this process. Lewis rat adipose-derived stem
      cells were isolated and grafted (3.0 * 10(5) cells) to porcine ADM disks (1.5 mm
      thick * 6 mm diameter) using either passive onlay or interstitial injection
      seeding techniques. Following incubation, seeding efficiency and seeded cell
      viability were measured in vitro. In addition, Eighteen Lewis rats underwent
      subcutaneous placement of ADM disk either as control or seeded with PKH67 labeled
      ASCs. ADM disks were seeded with ASCs using either onlay or injection techniques.
      On day 7 and or 14, ADM disks were harvested and analyzed for host cell
      infiltration. Onlay and injection techniques resulted in unique seeding patterns;
      however cell seeding efficiency and cell viability were similar. In-vivo studies
      showed significantly increased host cell infiltration towards the ASCs foci
      following injection seeding in comparison to control group (p < 0.05). Moreover,
      regional endothelial cell invasion was significantly greater in ASCs injected
      grafts in comparison to onlay seeding (p < 0.05). ADM can successfully be
      engrafted with ASCs. Interstitial engraftment of ASCs into ADM via injection
      enhances regional infiltration of host cells and angiogenesis, whereas onlay
      seeding showed relatively broad and superficial cell infiltration. These findings
      may be applied to improve the incorporation of avascular engineered constructs.

PMID- 23554079
TI  - Effect of bixin and norbixin on the expression of cytochrome P450 in HepG2 cell
      line.
AB  - Bixin and norbixin are the main components of annatto, which is extracted from
      Bixa orellana and largely used as natural colorant in the food and pharmaceutical
      industries. Annatto can enhance CYP1A and CYP2B activity in rats; however, the
      inducer effect has not been investigated in human cell lines. In this study, the
      ability of bixin and norbixin to induce the cytochrome P450 (CYP) enzymes was
      assessed in HepG2 human hepatoma cell line. HepG2 cells were treated with bixin
      and norbixin, and the expression of the CYP genes quantified by real-time reverse
      transcription polymerase chain reaction (RT-PCR). Expression of CYP1A1 and CYP1A2
      was significantly increased by bixin treatment, while CYP2B6, 2C9, 2E1 and 3A4
      were unaffected. Cells were treated with norbixin showed no inducer effect. The
      results suggest that the inducer potential of annatto is attributed to bixin, but
      not to norbixin, despite their similarities in molecular structure. 

PMID- 23554078
TI  - Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility
      and proliferation.
AB  - SCOPE: A key event in the development of plaque in the arteries is the migration
      and proliferation of smooth muscle cells (SMCs) from the media to the intima of
      the blood vessel. This study was conducted to evaluate the effects of
      bisdemethoxycurcumin (BC), a naturally occurring structural analog of curcumin
      (CC), on platelet-derived growth factor (PDGF)-stimulated migration and
      proliferation of SMCs. METHODS AND RESULTS: CC and BC were synthesized by
      condensing acetyl acetone with vanillin and 4-hydroxybenzaldehyde, respectively.
      SMCs isolated from adult rat aorta were stimulated with PDGF in the presence or
      absence of CC or BC following which, cell migration and proliferation were
      assessed by monolayer wound healing assay and [(3) H]-thymidine incorporation
      respectively. PDGF-stimulated phosphorylation of PDGF receptor-beta and its
      downstream effectors Akt and ERK were assessed by Western blotting. Intracellular
      reactive oxygen species was assessed using the fluorescent dye 5-(6)-chloromethyl
      2',7'-dichlorodihydrofluorescein diacetate. BC elicited a concentration-dependent
      inhibition of PDGF-stimulated phosphorylation of PDGF receptor-beta, Akt and Erk
      as well as the PDGF-stimulated SMC migration and proliferation. BC was more
      potent than CC in inhibiting migration and proliferation and suppressing PDGF
      signaling in SMCs. Both compounds were equipotent in inhibiting PDGF-stimulated
      generation of intracellular reactive oxygen species. CONCLUSION: BC may be of
      potential use in the prevention or treatment of vascular disease.

PMID- 23554080
TI  - Disproportionality signal of progressive multifocal leukoencephalopathy:
      monoclonal antibodies versus other immunosuppressants.

PMID- 23554081
TI  - Depressive disorders among children in the transforming China: an epidemiological
      survey of prevalence, correlates, and service use.
AB  - BACKGROUND: To date, no one-phase survey of childhood depression has been
      performed in China that involves both urban and rural community children. The
      objective of this study was to determine the prevalence, correlates, and mental
      health service utilization of depressive disorders (DDs) in a community-based
      sample of 6-14-year-old children in south-central China. METHODS: Children
      (3,582) were approached through multistage sampling and interviewed using a
      Chinese version of the Mini International Neuropsychiatric Interview for Children
      and Adolescents 5.0, which is a structured interview that is administered by
      trained psychiatrists to obtain information from children and their guardians.
      RESULTS: The overall prevalence of all current DDs was found to be 2.8% (95%CI:
      1.5-3.9). The risk factors for depression included being 9-14-year old, not
      attending school, having unmarried parents, living in a non-nuclear family
      (single parent or parentless family), being taken care of by people other than
      two parents (single parent, grandparent(s), other relatives, or others) during
      the past year, and not being breastfed prior to 1 year of age. Only 5.8% of the
      depressed children had received professional help prior to the interview.
      CONCLUSIONS: The prevalence of DDs among children in this part of China is
      relatively high compared with most figures reported in other countries.
      Depression in this age group has been a major public health concern, but it is
      often underrecognized. There is an urgent need to develop efficacious
      interventions aimed at the prevention and early recognition of childhood
      depression.

PMID- 23554082
TI  - Incidence and risk factors of significant carotid artery stenosis in asymptomatic
      survivors of head and neck cancer after radiotherapy.
AB  - BACKGROUND: The incidence and risk factors of carotid artery stenosis in
      asymptomatic patients after head and neck radiation therapy (RT) are unknown.
      METHODS: This retrospective study reviewed asymptomatic patients treated with RT
      for head and neck cancer from 2000 to 2009 who underwent screening carotid
      ultrasound. RESULTS: Two hundred twenty-four patients were included, the majority
      of whom had stage III to IV disease and received cisplatin-based chemotherapy.
      Median time from RT completion to last carotid ultrasound was 3 years. Actuarial
      rate of carotid artery stenosis at 4 years was 14% (95% confidence interval [CI],
      4% to 22%). Multivariate analysis revealed that carotid artery stenosis was
      associated with Framingham risk factors (hazard ratio [HR], 1.6 per factor; 95%
      CI, 1.2-2.2; p = .003). Among 135 patients treated with intensity-modulated
      radiation therapy (IMRT), the HR for carotid artery stenosis was 1.4 for every 10
      Gy increase in mean RT dose to the carotid bulb plus 2 cm (95% CI, 0.8-2.4; p =
      .35). CONCLUSION: Prevention and screening programs should be considered for head
      and neck cancer survivors given the high risk of carotid artery stenosis.

PMID- 23554083
TI  - The stress response resolution assay. I. Quantitative assessment of environmental
      agent/condition effects on cellular stress resolution outcomes in epithelium.
AB  - The events or factors that lead from normal cell function to conditions and
      diseases such as aging or cancer reflect complex interactions between cells and
      their environment. Cellular stress responses, a group of processes involved in
      homeostasis and adaptation to environmental change, contribute to cell survival
      under stress and can be resolved with damage avoidance or damage tolerance
      outcomes. To investigate the impact of environmental agents/conditions upon
      cellular stress response outcomes in epithelium, a novel quantitative assay, the
      "stress response resolution" (SRR) assay, was developed. The SRR assay consists
      of pretreatment with a test agent or vehicle followed later by a calibrated
      stress conditions exposure step (here, using 6-thioguanine). Pilot studies
      conducted with a spontaneously-immortalized murine mammary epithelial cell line
      pretreated with vehicle or 20 ug N-ethyl-N-nitrososurea/ml medium for 1 hr, or
      two hTERT-immortalized human bronchial epithelial cell lines pretreated with
      vehicle or 100 uM zidovudine/lamivudine for 12 days, found minimal alterations in
      cell morphology, survival, or cell function through 2 weeks post-exposure.
      However, when these pretreatments were followed 2 weeks later by exposure to
      calibrated stress conditions of limited duration (for 4 days), significant
      alterations in stress resolution were observed in pretreated cells compared with
      vehicle-treated control cells, with decreased damage avoidance survival outcomes
      in all cell lines and increased damage tolerance outcomes in two of three cell
      lines. These pilot study results suggest that sub-cytotoxic pretreatments with
      chemical mutagens have long-term adverse impact upon the ability of cells to
      resolve subsequent exposure to environmental stressors.

PMID- 23554084
TI  - Response inhibition in motor conversion disorder.
AB  - Conversion disorders (CDs) are unexplained neurological symptoms presumed to be
      related to a psychological issue. Studies focusing on conversion paralysis have
      suggested potential impairments in motor initiation or execution. Here we studied
      CD patients with aberrant or excessive motor movements and focused on motor
      response inhibition. We also assessed cognitive measures in multiple domains. We
      compared 30 CD patients and 30 age-, sex-, and education-matched healthy
      volunteers on a motor response inhibition task (go/no go), along with verbal
      motor response inhibition (color-word interference) and measures of attention,
      sustained attention, processing speed, language, memory, visuospatial processing,
      and executive function including planning and verbal fluency. CD patients had
      greater impairments in commission errors on the go/no go task (P < .001) compared
      with healthy volunteers, which remained significant after Bonferroni correction
      for multiple comparisons and after controlling for attention, sustained
      attention, depression, and anxiety. There were no significant differences in
      other cognitive measures. We highlight a specific deficit in motor response
      inhibition that may play a role in impaired inhibition of unwanted movement such
      as the excessive and aberrant movements seen in motor conversion. Patients with
      nonepileptic seizures, a different form of conversion disorder, are commonly
      reported to have lower IQ and multiple cognitive deficits. Our results point
      toward potential differences between conversion disorder subgroups. (c) 2013
      Movement Disorder Society.

PMID- 23554085
TI  - Protective induction of Hsp70 in heat-stressed primary myoblasts: Involvement of
      MAPKs.
AB  - The involvement of extracellular signal-regulated kinases 1 and 2 (ERK1,2),
      stress kinase p38 and c-Jun NH2 -terminal kinases 1 and 2 (JNK1,2) on Hsp70
      upregulation following mild heat shock, and resulting cell protection, was
      studied on rabbit primary myoblasts. Cells subjected to heat stress (42 degrees
      C; 60 min) showed a significantly enhanced amount of heat-shock-induced protein
      70 (Hsp70), correlating with sustained phosphorylation of MAP kinases ERK1,2,
      inhibition of p38 and JNK1,2 activation. Induced Hsp70 did not autocrinally
      suppress activation of transcription factor c-Jun, suggesting involvement of the
      latter in the protection of myoblasts following heat shock. The inhibition of
      stress kinases p38, JNK1,2, and MEK1,2 by SP600125, SB203580, and UO126,
      respectively, established the involvement of JNK1,2 and p38 as upstream, and
      ERK1,2 as downstream targets of Hsp70 induction. Moreover, the effect of the
      MEK1,2 inhibitor UO126 revealed a new pathway of c-Jun activation by ERK1,2 in
      myogenic heat-stressed stem cells. The presented data show that transient
      activation of JNK1, JNK2, and p38 is necessary for Hsp70 induction and ensuing
      cell protection. In conclusion, affecting myogenic stem cell protective
      mechanisms might be a useful strategy in improving stem cell survival and their
      expanded application in therapy.

PMID- 23554086
TI  - Impacts of silver nanoparticles on cellular and transcriptional activity of
      nitrogen-cycling bacteria.
AB  - The widespread use of silver nanoparticles (AgNPs) raises the potential for
      environmental releases that could impact microbial ecosystem services. In the
      present study, the authors address how the AgNPs and Ag(+) that they release may
      impact nitrogen-cycling bacteria. The authors studied the cellular and
      transcriptional response of the denitrifier Pseudomonas stutzeri, the nitrogen
      fixer Azotobacter vinelandii, and the nitrifier Nitrosomonas europaea exposed to
      35 nm (carbon-coated) AgNPs or to Ag(+) (added as AgNO3 ). Based on minimum
      inhibitory concentrations (MICs), Ag(+) was 20 times to 48 times more toxic to
      the tested strains than AgNPs (including Ag(+) released during exposure).
      Exposure to sublethal concentrations of AgNPs or Ag(+) (representing 10% of the
      respective MIC for AgNO3 ) resulted in no significant effect on the expression of
      the denitrifying genes narG, napB, nirH, and norB in P. stutzeri or the nitrogen
      fixing genes nifD, nifH, vnfD, and anfD in A. vinelandii, whereas nitrifying
      genes (amoA1 and amoC2) in N. europaea were upregulated (2.1- to 3.3-fold). This
      stimulatory effect disappeared at higher silver concentrations (60% of the Ag(+)
      MIC), and toxicity was exerted at concentrations higher than 60% of the Ag(+)
      MIC. The MIC for N. europaea was 8 times to 24 times lower than for the other
      strains, indicating higher susceptibility to AgNPs. This was corroborated by the
      lower half-lethal concentration for N. europaea (87 ug/L) compared with P.
      stutzeri (124 ug/L) and A. vinelandii (>250 ug/L) when cells were exposed with
      Ag(+) for 24 h in 1 mM bicarbonate buffer. This suggests that ammonia oxidation
      would be the most vulnerable nitrogen-cycling process in wastewater treatment
      plants receiving AgNPs and in agricultural soils amended with biosolids that
      concentrate them.

PMID- 23554087
TI  - Direct and selective production of propene from bio-ethanol on Sc-loaded IN2O3
      catalysts.
AB  - Propene, one of key building blocks for manufacturing plastics and chemicals,
      could be directly and stably produced from ethanol in good yields. The conversion
      degree of ethanol to propene reached approximately 60 mol% by using a 3 atom%
      scandium-loaded indium oxide catalyst at 823 K in the presence of water and
      hydrogen. The introduction of Sc prevented the reduction of In2O3 to In metal
      during the reaction, and that of water decreased the coke formation. Both
      additions resulted in longer lifetimes of the catalysts. The hydrogen addition
      increased the conversion of acetone to propene. The reaction pathways are also
      suggested on the basis of the product distributions and the pulse experiments,
      ethanol->acetaldehyde->acetone->propene, which is quite different from the shape
      selective catalysis on zeolites and the dimerization-metathesis of ethene on
      nickel ion-loaded silica catalysts.

PMID- 23554088
TI  - Intellectual disability and hemizygous GPD2 mutation.
AB  - We report on a 25-year-old female with intellectual disability, mildly unusual
      face, and a pervasive developmental disorder, in whom routine aCGH showed a 298
      kb de novo deletion at chromosome 2q24.1(156869529-157167986 * 1). The region
      contained two genes (NR4A2; GPD2). Molecular studies in the proposita showed an
      additional variant in GPD2 (c.614C > T, p.Pro205Leu), which was predicted to be
      pathogenic. The variant was also present in the healthy mother and sister.
      Functional analysis showed absent GPD2 activity in the proposita and 50% activity
      in mother and sister. We conclude that we have been able to find circumstantial
      evidence for the causative effect of the hemizygous GPD2 mutation but full proof
      remained lacking. Total costs for the work-up in these patients were high
      (?21,975 [$27,029]). Similar results will increasingly be found when Next
      Generation Techniques will be applied widely in patients with intellectual
      disability, and proving pathogenicity by functional studies or in animal models
      will be expensive. We advocate the use of freely accessible international
      databases combining phenotype and genotype data using standard nomenclatures to
      facilitate proving pathogenicity of research data and to decrease costs of health
      care.

PMID- 23554089
TI  - Portal vein arterialization using an accessory right hepatic artery in liver
      transplantation.
AB  - Portal vein thrombosis remains to be a challenging issue during liver
      transplantation even with the acquisition of innovative surgical techniques and
      years of experience. Most frequently, an initial eversion thromboendovenectomy is
      performed and depending on the extent of thrombosis and intraoperative findings,
      further revascularization options include venous jump grafts, portocaval
      hemitransposition, renoportal anastomosis or portal vein arterialization. Reports
      on these surgical approaches are limited although with acceptable outcomes. We
      present a 64-year-old patient with hepatitis C cirrhosis who underwent orthotopic
      liver transplantation with portal vein arterialization using an accessory right
      hepatic artery. Liver graft function has remained stable four years after
      transplant with notable aneurysmal dilatation of the portal vein.

PMID- 23554090
TI  - Enhanced activity and selectivity in catalytic methanol steam reforming by basic
      alkali metal salt coatings.

PMID- 23554091
TI  - Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract
      obstruction.
AB  - OBJECTIVES: Fetuses with pulmonary outflow tract obstruction (POTO) have altered
      blood flow to the pulmonary vasculature. We sought to determine whether pulmonary
      vascular impedance, as assessed by the pulsatility index (PI), is different in
      fetuses with POTO compared with normal controls. METHODS: Branch pulmonary artery
      PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses
      (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was
      performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary
      artery. The direction of flow in the ductus arteriosus was noted. The study and
      control groups were compared with Student's t-test and ANOVA. A linear mixed
      model evaluated the relationship between PI and ductus arteriosus flow patterns.
      RESULTS: There was no difference in PI between control, pulmonary stenosis and
      pulmonary atresia subjects at PA1 and PA2; however, there was a significant
      difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did
      controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with
      retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did
      those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was
      lower in fetuses that required prostaglandin postnatally than in those that did
      not (P=0.008). CONCLUSIONS: Fetuses with pulmonary atresia or severe pulmonary
      stenosis with retrograde flow in the ductus arteriosus have decreased PI in the
      distal pulmonary vasculature. Our findings indicate the capacity of the fetal
      pulmonary vasculature to vasodilate in response to anatomical obstruction of
      flow.

PMID- 23554092
TI  - Influence of cell culture medium composition on in vitro dissolution behavior of
      a fluoride-containing bioactive glass.
AB  - Bioactive glasses are used clinically for bone regeneration, and their
      bioactivity and cell compatibility are often characterized in vitro, using
      physiologically relevant test solutions. The aim of this study was to show the
      influence of varying medium characteristics (pH, composition, presence of
      proteins) on glass dissolution and apatite formation. The dissolution behavior of
      a fluoride-containing bioactive glass (BG) was investigated over a period of one
      week in Eagle's Minimal Essential Medium with Earle's Salts (MEM), supplemented
      with either, (a) acetate buffer, (b) 4-(2-hydroxyethyl)-1
      piperazineethanesulfonic acid (HEPES) buffer, (c) HEPES + carbonate, or (d) HEPES
      + carbonate + fetal bovine serum. Results show pronounced differences in pH, ion
      release, and apatite formation over 1 week: Despite its acidic pH (pH 5.8 after
      BG immersion, as compared to pH 7.4-8.3 for HEPES-containing media), apatite
      formation was fastest in acetate buffered (HEPES-free) MEM. Presence of carbonate
      resulted in formation of calcite (calcium carbonate). Presence of serum proteins,
      on the other hand, delayed apatite formation significantly. These results confirm
      that the composition and properties of a tissue culture medium are important
      factors during in vitro experiments and need to be taken into consideration when
      interpreting results from dissolution or cell culture studies.

PMID- 23554093
TI  - Transcatheter closure of perimembranous ventricular septal defect using Amplatzer
      ductal occluder.
AB  - OBJECTIVE: To show that transcatheter closure of perimembranous ventricular
      septal defect (PMVSD) with the Amplatzer ductal occluder (ADO, AGA Medical Corp,
      Plymouth, Minnesota) is a safe and effective treatment option. BACKGROUND:
      Transcatheter closure of PMVSD is a challenging procedure. Recently, the
      Amplatzer PMVSD occluder (APMVSDO, AGA Medical Corp, Plymouth, Minnesota) has
      been shown to be effective in closing hemodynamically significant PMVSDs.
      However, the high incidence of complete atrioventricular block (CAVB) after
      device occlusion of a PMVSD has been a hot issue as well. METHODS: Among several
      devices used in closing PMVSD percutaneously, we prefer the ADO because of the
      anatomic resemblance between PMVSD with aneurysm and patent ductus arteriosus,
      and it has no right ventricular disc which may contribute to the occurrence of
      CAVB. RESULTS: Between August 2009 and May 2012, 21 patients (5 males and 16
      females) underwent percutaneous PMVSD closure using ADO. The patients' ages
      ranged from 3 to 42 years (median: 7 years), and their weights ranged from 18 kg
      to 60 kg (median: 27 kg). All patients showed echocardiographic signs of left
      ventricular volume overload and trivial to small mitral regurgitation (Qp/Qs =
      1.7 +/- 0.4). The mean defect size of the right ventricular side was 4.3 +/- 1.0
      mm. Devices 2 mm larger than the measured narrowest VSD diameter were selected in
      most patients. The ADOs were successfully implanted in all patients without any
      significant complications except one transient CAVB, one case of delivery wire
      fracture, and one case of surgery due to significant residual leak. Small
      residual shunts were observed immediately after the device implantation, but they
      disappeared during follow-up for 18 of 20 patients. The mean follow-up period was
      20 +/- 9 months, and CAVB or aortic regurgitation was not observed in all
      patients. CONCLUSION: Transcatheter closure of PMVSD with the ADO is a safe and
      promising treatment option, but long-term follow-up in a large number of patients
      would be warranted.

PMID- 23554094
TI  - Auto-calibration approach for k-t SENSE.
AB  - PURPOSE: The goal of this work is to increase the spatial resolution of training
      data, used by reconstruction methods such as k-t SENSE in order to calculate the
      missing data in a series of dynamic images, without compromising their temporal
      resolution or acquisition time. THEORY: The k-t SENSE method allows dynamic
      imaging at high acceleration factors with high reconstruction quality. However,
      the low resolution training data required by k-t SENSE may cause undesired
      temporal filtering effects in the reconstructed images. METHODS: In this work, a
      feedback regularization approach is applied to realize auto-calibration of the k
      t SENSE algorithm. To that end, a full resolution training data set is calculated
      from the accelerated data itself using a TSENSE reconstruction. The reconstructed
      training data are then fed back for the actual k-t SENSE reconstruction. For
      evaluation of our approach, temporal filtering effects are quantified by
      calculating the modulation transfer function and noise measurements are done by
      Monte-Carlo simulations. RESULTS: Computer simulations and cardiac imaging
      experiments demonstrate an improved temporal fidelity of auto-calibrated k-t
      SENSE compared to standard k-t SENSE. CONCLUSION: Auto-calibrated k-t SENSE
      provides high quality reconstructions for dynamic imaging applications.

PMID- 23554095
TI  - Expression, purification and proteomic analysis of recombinant histone H4
      acetylated at lysine 16.
AB  - Many histone covalent modifications have been identified and shown to play key
      regulatory roles in eukaryotic transcription, DNA damage repair, and replication.
      In vitro experiments designed to understand the mechanistic role of individual
      modifications require the availability of substantial quantities of pure
      histones, homogeneously modified at specific residues. We have applied the amber
      stop codon/suppressor tRNA strategy to the production of histone H4 acetylated at
      lysine 16, a particularly important isoform of this histone. Our success relies
      on adapting the H4 DNA sequence to the codon preference of E. coli and on
      preventing the premature decay of the H4 mRNA. These modifications to the
      original procedure render it easily applicable to the generation of any
      covalently modified histone H4 isoform.

PMID- 23554096
TI  - Internet-mediated physician-patient interaction focusing on extracranial
      hemangiomas and vascular malformations.
AB  - BACKGROUND: Internet-mediated communication in health care is becoming
      increasingly important. The purpose of this study was to analyze internet
      mediated physician-patient interaction in an angioma center. METHODS: Patient
      related e-mails received between January 2002 and June 2009 were retrospectively
      analyzed regarding the diagnosis of hemangiomas or vascular malformations.
      Additionally, the visitors' statistics of the corresponding website
      ''www.angiome.de" was evaluated. RESULTS: Five hundred forty-eight e-mails
      matched the criteria of the study. From 2002 to 2008, the number of messages
      registered annually increased by a factor of 20 and the average number of e-mails
      per patient tripled. The number of new patients contacting the center via e-mail
      increased from 12 to 72 per year. The website ''www.angiome.de" was visited 8490
      times in 2008 and 13,291 times in 2009. CONCLUSION: The presence of the internet
      is relevant to get in touch with new patients and to provide information for
      nonprofessionals and experts especially in diseases with low incidence.

PMID- 23554097
TI  - Are we teaching enough anatomy?

PMID- 23554098
TI  - Secretion of growth factors from macrophages when cultured with microparticles.
AB  - The aim of this study is to investigate the influence of macrophages on
      osteoblast (OB) performance and differentiation. In this regard, we studied the
      secretion of growth factors including bone morphogenetic proteins (BMPs) from
      before and after activation of macrophages. We also evaluated osteogenic markers
      in the co-culture of macrophages and OBs. The macrophages were seeded on
      microparticles (MPs) based on chitosan (CS). Two types of MPs were fabricated
      including CS MPs and 10% calcium phosphate (CaHPO4 )-incorporated CS MPs.
      Macrophage seeded on MPs was activated using lipopolysaccharide (LPS). The
      expression of BMP-2, BMP-6, BMP-7, and transforming growth factor beta (TGF-beta)
      from macrophages seeded and cultured on hybrid MPs before and after activation of
      LPS at predetermined times was quantified using a quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). All of the above growth factors
      were expressed from MP-macrophage cultures before LPS activation. Osteogenic
      markers such as alkaline phosphatase (ALP), osteocalcin (OCN), and collagen I
      (COL-I) in the cultures of MP-OB-macrophage were quantified using a quantitative
      RT-PCR at days 2, 4, and 7. We found an elevation of gene expression of ALP and
      COL-1 in the co-cultures of OB-macrophage on MPs compared to OB on MP cultures.
      These data suggest that macrophages enhance expression of osteogenic markers in
      OBs, and demonstrate the importance of the role of macrophages in bone
      regeneration.

PMID- 23554099
TI  - Male pattern baldness and its association with coronary heart disease: a meta
      analysis.
AB  - OBJECTIVE: To confirm the association between male pattern baldness and coronary
      heart disease (CHD). DESIGN: Meta-analysis of observational studies. DATA
      SOURCES: Medline and the Cochrane Library were searched for articles published up
      to November 2012 using keywords that included both 'baldness' and 'coronary heart
      disease' and the reference lists of those studies identified were also searched.
      STUDY SELECTION: Observational studies were identified that reported risk
      estimates for CHD related to baldness. Two observers independently assessed
      eligibility, extracted data and assessed the possibility of bias. DATA SYNTHESIS:
      The adjusted relative risk (RR) and 95% CI were estimated using the DerSimonian
      Laird random-effect model. RESULTS: 850 possible studies, 3 cohort studies and 3
      case-control studies were selected (36 990 participants). In the cohort studies,
      the adjusted RR of men with severe baldness for CHD was 1.32 (95% CI 1.08 to
      1.63, p=0.008, I(2)=25%) compared to those without baldness. Analysis of younger
      men (<55 or <=60 years) showed a similar association of CHD with severe baldness
      (RR 1.44, 95% CI 1.11 to 1.86, p=0.006, I(2)=0%). In three studies employing the
      modified Hamilton scale, vertex baldness was associated with CHD and the relation
      depended on the severity of baldness (severe vertex: RR 1.48 (1.04 to 2.11,
      p=0.03); moderate vertex: RR 1.36 (1.16 to 1.58, p<0.001); mild vertex: RR 1.18
      (1.04 to 1.35, p<0.001)). However, frontal baldness was not associated with CHD
      (RR 1.11 (0.92 to 1.32, p=0.28)). CONCLUSIONS: Vertex baldness, but not frontal
      baldness, is associated with an increased risk of CHD. The association with CHD
      depends on the severity of vertex baldness and also exists among younger men.
      Thus, vertex baldness might be more closely related to atherosclerosis than
      frontal baldness, but the association between male pattern baldness and CHD
      deserves further investigation.

PMID- 23554100
TI  - Epitope mapping of the major allergen from Atlantic cod in Spanish population
      reveals different IgE-binding patterns.
AB  - SCOPE: IgE-epitope mapping of allergens reveal important information about
      antigen components involved in allergic reactions. The peptide-based microarray
      immunoassay has been used to map epitopes of some food allergens. We developed a
      peptide microarray immunoassay to map allergenic epitopes in parvalbumin from
      Atlantic cod (Gad m 1), the most consumed cod species in Spain. METHODS AND
      RESULTS: Sera from 13 fish-allergic patients with specific IgE to cod parvalbumin
      were used. A library of overlapping peptides was synthesized, representing the
      primary sequence of Gad m 1. Peptides were used to analyze allergen-specific IgE
      antibodies in patient sera. 100% of the patients recognized one antigenic region
      of 15 amino acids in length in Gad m 1. This region only partially correlated
      with one of the three antigenic determinants of Gad c 1 (Allergen M), parvalbumin
      from Baltic cod (Gadus callarias). In the 3D model of the protein, this region
      was located on the surface of the protein. CONCLUSION: We have identified a
      relevant antigenic region in Gad m 1. This epitope could be considered as a
      severity marker and provides additional information to improve fish allergy
      diagnosis and the design of safe immunotherapeutic tools.

PMID- 23554101
TI  - The chalcone 2'-hydroxy-4',5'-dimethoxychalcone activates death receptor 5
      pathway and leads to apoptosis in human nonsmall cell lung cancer cells.
AB  - Natural chalcones have been proved to inhibit cancer cells with therapeutic
      potential, but the underlying molecular mechanism is still largely unexplored.
      Here, we identified a novel chalcone, 2'-hydroxy-4',5'-dimethoxychalcone (HDMC)
      and demonstrated that HDMC induced apoptosis in various nonsmall cell lung cancer
      cells. Further study showed that HDMC elevated cellular reactive oxygen species
      (ROS) levels, thus inducing expressions of ATF4 and C/EBP homologous protein
      (CHOP). Then, death receptor 5 (DR5) was upregulated through ATF4-CHOP axis and
      eventually resulted in apoptosis. We also found that downregulation of c-FLIPL
      contributed to HDMC-induced apoptosis. In conclusion, HDMC induces apoptosis in
      human nonsmall cell lung cancer cells via activation of DR5 signaling pathway,
      and ROS-mediated ATF4-CHOP axis is involved in the process. Our results further
      supported the potential for HDMC to be developed as a new antitumor agent for
      cancer therapy or chemoprevention.

PMID- 23554103
TI  - Flavonols enhanced production of anti-inflammatory substance(s) by
      Bifidobacterium adolescentis: prebiotic actions of galangin, quercetin, and
      fisetin.
AB  - The gut microbiota is capable of the bioconversion of flavonoids whereas
      influences of probiotic anaerobes on the bioactivities of flavonoids and vice
      versa are still unclear. Here, we investigated functional interactions with
      respect to the anti-inflammatory activity between flavonols and probiotic
      bacteria. Ten enteric (6 probiotic and 4 indigenous) bacteria were incubated with
      flavonols (galangin, kaempferol, quercetin, myricetin, and fisetin) under
      anaerobic conditions, and the supernatants were assessed for their effects on
      nitric oxide (NO) production in lipopolysaccaride-stimulated RAW264 cells.
      Although the conditioned medium from the flavonol mono-culture and almost all of
      the tested co-cultures failed to inhibit NO production, the medium from the
      Bifidobacterium adolescentis/flavonols (galangin, quercetin, and fisetin) co
      culture highly suppressed NO production. This activity increased during the 1-6 H
      incubation in a time-dependent manner and was not observed in the co-culture
      using heat-inactivated B. adolescentis. Interestingly, when the B. adolescentis
      cell number was increased, the supernatant from the mono-culture of the bacteria
      showed NO suppression, suggesting that B. adolescentis may produce NO
      suppressant(s), and flavonols may have a promoting effect. These findings
      indicate that flavonols have a prebiotic-like effect on the anti-inflammatory
      activity of B. adolescentis.

PMID- 23554104
TI  - Behavioral excesses in depression: a learning theory hypothesis.
AB  - This paper reviews two learning theory-based models of experiential contributions
      to depression: response contingent positive reinforcement and learned
      helplessness. The authors argue that these models connect to a phenomenon that
      may explain why symptoms of behavioral excess (e.g. rumination) often occur in
      depression that is otherwise marked by symptoms of behavioral deficit (e.g.
      anhedonia). Specifically, the authors illustrate that that concept of schedule
      strain (or low rates of response contingent reinforcement giving rise to low
      frequencies of behavior) unites these models. Depression is more likely, or more
      severe, when schedule strain conditions occur in situations containing
      reinforcers important to the individual and/or when they simultaneously occur in
      a number of situations. Conditions of schedule strain are known to give rise to
      adjunctive behaviors: apparently irrelevant, easy behaviors that deliver
      immediate reinforcement. This paper suggests that, for some depressed
      individuals, behavioral excess symptoms like rumination and overeating might
      serve adjunctive functions. Implications of this hypothesis are discussed.

PMID- 23554105
TI  - Observations of limited secondary effects to benthic invertebrates and
      macrophytes with activated carbon amendment in river sediments.
AB  - Amendment of activated carbon to sediments has been shown to effectively reduce
      the bioavailability of hydrophobic organic contaminants, but concerns have been
      raised about the potential toxicological impacts of administering a strong
      sorbent into sediments. The present study provides a summary of several
      investigations carried out as part of a pilot-scale study in a river to
      understand the secondary effects of activated carbon added to reduce the
      bioavailability of sediment-associated polychlorinated biphenyls. While some
      previous laboratory amendment studies have found reduced lipid content in
      freshwater worms exposed to activated carbon-treated sediments, the authors did
      not observe an impact with fine-granular activated carbon-amended sediments aged
      in the field. Benthic community studies did not find differences between control
      and activated carbon-treated field sites over 3 yr of postapplication monitoring.
      Laboratory studies with submerged aquatic plants indicated reduced growth in
      sediments amended with >=5% activated carbon, which was attributed to volume
      dilution of nutritional sediment or bulk density changes and was also observed
      when the sediment was amended with biochar and inert perlite. Since in situ
      sorbent amendment is likely to be implemented in depositional sediment
      environments, potential negative impacts will likely be short-term if the treated
      site is slowly covered with new sediment over time. Overall suitability of
      activated carbon amendment for a site will depend on balancing ecosystem and
      human health benefits from contaminant bioavailability reduction with any
      potential negative impacts expected under field conditions.

PMID- 23554102
TI  - Emerging mechanisms of glutathione-dependent chemistry in biology and disease.
AB  - Glutathione has traditionally been considered as an antioxidant that protects
      cells against oxidative stress. Hence, the loss of reduced glutathione and
      formation of glutathione disulfide is considered a classical parameter of
      oxidative stress that is increased in diseases. Recent studies have emerged that
      demonstrate that glutathione plays a more direct role in biological and
      pathophysiological processes through covalent modification to reactive cysteines
      within proteins, a process known as S-glutathionylation. The formation of an S
      glutathionylated moiety within the protein can lead to structural and functional
      modifications. Activation, inactivation, loss of function, and gain of function
      have all been attributed to S-glutathionylation. In pathophysiological settings,
      S-glutathionylation is tightly regulated. This perspective offers a concise
      overview of the emerging field of protein thiol redox modifications. We will also
      cover newly developed methodology to detect S-glutathionylation in situ, which
      will enable further discovery into the role of S-glutathionylation in biology and
      disease.

PMID- 23554106
TI  - Synthesis of molecular frameworks containing two distinct heterocycles connected
      in a single molecule with enhanced three-dimensional shape diversity.
AB  - Herein, we report the synthesis of fused-triazole scaffolds that are connected by
      pyrimidines, pyrazoles, or pyrazolopyrimidines through carbohydrate-derived
      stereodivergent linkers. Pyrimidine-, pyrazole-, or pyrazolopyrimidine-based
      carbohybrids were constructed through condensations of the key intermediates, 2-C
      formyl glycals, with various dinucleophiles. Fused-triazole scaffolds were
      obtained through intramolecular 1,3-dipolar cycloadditions after selective
      functionalization of the carbohybrid polyol moieties with azide and alkyne
      functionalities using SN 2-type alkylations or Mitsunobu reactions. Overall, this
      synthetic method affords two distinct privileged substructures in a single
      molecule, connected by stereodivergent diol linkers derived from abundant natural
      chiral sources, namely, carbohydrates. The resulting vicinal diols in the linker
      were further modified to achieve unique connectivities between the two privileged
      structures for maximized three-dimensional shape diversity, which we called the
      linker diversification strategy.

PMID- 23554107
TI  - Prodromal autonomic symptoms and signs in Parkinson's disease and dementia with
      Lewy bodies.
AB  - Pathologic staging systems suggest that autonomic dysfunction may be an early
      manifestation of Parkinson's disease and dementia with Lewy bodies. However,
      direct evidence is limited, and no prospective studies have measured when
      autonomic dysfunction starts before disease. Patients with idiopathic rapid eye
      movement (REM) sleep behavior disorder are at very high risk of developing
      neurodegenerative synucleinopathy, providing an opportunity to directly observe
      the development of autonomic dysfunction from prodromal stages of
      neurodegeneration. Patients with idiopathic REM sleep behavior disorder were
      followed annually in a prospective cohort that was established in 2004. Urinary,
      orthostatic, erectile, and constipation symptoms and systolic blood pressure drop
      from lying to standing were assessed annually. Patients who eventually developed
      defined synucleinopathy were compared with age-matched controls. The evolution of
      autonomic measures was assessed with regression analysis to determine when
      markers first deviated from control values. Sensitivity and specificity of
      autonomic markers for identification of prodromal disease were calculated. Of 91
      patients, 32 developed disease. In prodromal stages, there was substantial
      autonomic dysfunction observable at least 5 years before diagnosis. On regression
      analysis, autonomic dysfunction appeared to progress slowly over prodromal
      periods. The estimated onset of autonomic dysfunction ranged from 11 years to 20
      years, and systolic drop (20.4 years) and constipation (15.3 years) had the
      earliest estimates. Systolic drop, erectile dysfunction, and constipation could
      identify disease up to 5 years before diagnosis with sensitivity ranging from 50%
      to 90%. By directly observing development of neurodegenerative synucleinopathy,
      we confirmed that autonomic dysfunction can occur early in neurodegenerative
      synucleinopathy, even as long as 20 years before defined disease. (c) 2013
      Movement Disorder Society.

PMID- 23554108
TI  - Response to: Design of a core classification process for DNA mismatch repair
      variations of a priori unknown functional significance.

PMID- 23554109
TI  - Natural Language Processing to identify pneumonia from radiology reports.
AB  - PURPOSE: This study aimed to develop Natural Language Processing (NLP) approaches
      to supplement manual outcome validation, specifically to validate pneumonia cases
      from chest radiograph reports. METHODS: We trained one NLP system, ONYX, using
      radiograph reports from children and adults that were previously manually
      reviewed. We then assessed its validity on a test set of 5000 reports. We aimed
      to substantially decrease manual review, not replace it entirely, and so, we
      classified reports as follows: (1) consistent with pneumonia; (2) inconsistent
      with pneumonia; or (3) requiring manual review because of complex features. We
      developed processes tailored either to optimize accuracy or to minimize manual
      review. Using logistic regression, we jointly modeled sensitivity and specificity
      of ONYX in relation to patient age, comorbidity, and care setting. We estimated
      positive and negative predictive value (PPV and NPV) assuming pneumonia
      prevalence in the source data. RESULTS: Tailored for accuracy, ONYX identified
      25% of reports as requiring manual review (34% of true pneumonias and 18% of non
      pneumonias). For the remainder, ONYX's sensitivity was 92% (95% CI 90-93%),
      specificity 87% (86-88%), PPV 74% (72-76%), and NPV 96% (96-97%). Tailored to
      minimize manual review, ONYX classified 12% as needing manual review. For the
      remainder, ONYX had sensitivity 75% (72-77%), specificity 95% (94-96%), PPV 86%
      (83-88%), and NPV 91% (90-91%). CONCLUSIONS: For pneumonia validation, ONYX can
      replace almost 90% of manual review while maintaining low to moderate
      misclassification rates. It can be tailored for different outcomes and study
      needs and thus warrants exploration in other settings.

PMID- 23554110
TI  - An injectable and biodegradable hydrogel based on poly(alpha,beta-aspartic acid)
      derivatives for localized drug delivery.
AB  - An injectable hydrogel via hydrazone cross-linking was prepared under mild
      conditions without addition of cross-linker or catalyst. Hydrazine and aldehyde
      modified poly(aspartic acid)s were used as two gel precursors. Both of them are
      water-soluble and biodegradable polymers with a protein-like structure, and
      obtained by aminolysis reaction of polysuccinimide. The latter can be prepared by
      thermal polycondensation of aspartic acid. Hydrogels were prepared in PBS
      solution and characterized by different methods including gel content and
      swelling, Fourier transformed-infrared spectroscopy, and in vitro degradation
      experiment. A scanning electron microscope viewed the interior morphology of the
      obtained hydrogels, which showed porous three-dimensional structures. Different
      porous sizes were present, which could be well controlled by the degree of
      aldehyde substitution in precursor poly(aspartic acid) derivatives. The
      doxorubicin-loaded hydrogels were prepared and showed a pH-sensitive release
      profile. The release rate can be accelerated by decreasing the environmental pH
      from a physiological to a weak acidic condition. Moreover, the cell adhesion and
      growth behaviors on the hydrogel were studied and the polymeric hydrogel showed
      good biocompatibility.

PMID- 23554111
TI  - Three-dimensional ultrasound imaging of an intrauterine device showing copper
      corrosion.

PMID- 23554112
TI  - The financial value of fellowship training in otolaryngology.
AB  - OBJECTIVE: To evaluate the financial impact of pursuing a fellowship in
      otolaryngology. STUDY DESIGN: Retrospective financial analysis using American
      Academy of Otolaryngology-Head and Neck Surgery survey data. SUBJECTS AND
      METHODS: The American Academy of Otolaryngology-Head and Neck Surgery report,
      entitled Socioeconomic Study among Members April 2011, gives a financial profile
      of respondents who reported their primary area of specialization as either
      general otolaryngology or a specific area of subspecialization. Weighted averages
      were calculated from the reported data. The weighted averages were used to
      calculate a net present value (NPV) over a 30-year contiguous career. RESULTS:
      The NPV for general otolaryngology was $4.73 million. The NPV for the following
      subspecialties in relation to general otolaryngology were (in hundred thousands)
      as follows: otolaryngologic allergy (-$1153), sleep medicine (-$677),
      otology/neurotology (-$339), laryngology (-$288), head and neck (-$191),
      pediatric otolaryngology (-$176), facial plastic surgery (-$139), skull base
      surgery ($122), rhinology ($285), and allergy and immunology ($350). Ninety-four
      percent of general otolaryngology respondents were in private practice. Most
      subspecialists worked in an academic setting. CONCLUSION: Fellowship training in
      otolaryngology will affect career earnings of prospective fellows. The overall
      financial impact of fellowship training, calculating in the delay in receiving a
      full clinical salary, should be factored into the decision to pursue fellowship
      training.

PMID- 23554113
TI  - Psychometric evaluation of the Sinonasal Outcome Test-16 and activity impairment
      assessment in acute bacterial sinusitis.
AB  - OBJECTIVE: To validate the Sinonasal Outcome Test-16 and Activity Impairment
      Assessment in patients with acute bacterial sinusitis. STUDY DESIGN: Data were
      used from a phase III clinical trial designed to evaluate the efficacy and safety
      of moxifloxacin 400 mg once daily for 5 consecutive days in the treatment of
      acute bacterial sinusitis. The psychometric properties and factor structure of
      the 2 measures were assessed. SETTING: Participants were given the measures to
      self-complete using either a telephone voice response system or a paper-and
      pencil format. SUBJECTS AND METHODS: Three hundred seventy-four patients with
      acute bacterial sinusitis were used in the analysis. Patients received either a
      placebo or 400 mg moxifloxacin once daily. Patients were then reviewed at test of
      cure and follow-up. All analyses were conducted on a combined sample of placebo
      and active treatment patients. RESULTS: The Sinonasal Outcome Test-16 was
      associated with minimal missing data at baseline but a higher proportion by test
      of cure. There was no evidence of floor or ceiling effects and no significant
      skew. The Activity Impairment Assessment also had low missing data at baseline
      and no obvious floor or ceiling effects, but the data were not normally
      distributed. Both measures had good internal consistency. Convergent and
      divergent validity as well as sensitivity and the minimally important difference
      are also reported. CONCLUSION: The measures both have good psychometric
      properties and are suitable for use with patients with acute bacterial sinusitis.
      Both instruments are sensitive. The minimal important difference estimates for
      the Sinonasal Outcome Test-16 are quite high but are similar to estimates
      reported previously.

PMID- 23554114
TI  - Supraclavicular artery island flap (SCAIF) vs free fasciocutaneous flaps for head
      and neck reconstruction.
AB  - OBJECTIVE: At our institution, the supraclavicular artery island flap (SCAIF) has
      become a reliable option for fasciocutaneous coverage of complex head and neck
      (H&N) defects. We directly compare the outcomes of reconstructions performed with
      SCAIFs and free fasciocutaneous flaps (FFFs), which have not been reported
      previously. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic
      medical center. SUBJECTS AND METHODS: Retrospective review of consecutive single
      surgeon H&N reconstructions using fasciocutaneous flaps over 5 years.
      Reconstructions were divided into 2 groups: SCAIFs and FFFs. Patient
      demographics, surgical parameters, and outcomes were compared statistically
      between groups. RESULTS: Thirty-four flaps were used in H&N reconstruction (18
      SCAIFs and 16 FFFs). There was no difference in patient demographics,
      distribution of defects, or follow-up (SCAIF 9.2 vs FFF 15.13 months, P = .65)
      between the 2 groups. The SCAIFs were larger than the FFFs (164.6 +/- 60 vs 111
      +/- 68 cm(2), P < .05) and had shorter total operative times (588 +/- 131 vs 816
      +/- 149 minutes, P < .05). Intensive care unit (ICU) length of stay was shorter
      for the SCAIF vs the FFF group (1.8 vs 5.6 days, P < .05). Overall morbidity was
      not significantly different (SCAIF 39% vs FFF 44%, P = NS). CONCLUSION: The SCAIF
      is a technically simpler and equally reliable sensate fasciocutaneous flap for
      H&N reconstruction with comparable outcomes, shorter operative time, less ICU
      stay, and no need for postoperative monitoring when compared with using FFFs. It
      should be considered a first-choice reconstructive option for complex H&N
      defects.

PMID- 23554115
TI  - The supraclavicular artery island flap (SCAIF) for head and neck reconstruction:
      surgical technique and refinements.
AB  - OBJECTIVE: We have found the supraclavicular artery island flap (SCAIF) to be a
      reliable, first-line tool for the reconstruction of complex head and neck
      defects. Here, we review our technique of flap elevation and summarize the
      current literature citing important contributions in the evolution of this flap.
      DATA SOURCES: Medline literature review of supraclavicular artery island flap or
      shoulder flap in head and neck reconstruction with particular emphasis on
      developments within the past 5 years. REVIEW METHODS: Literature review of
      technique, indications, anatomy, modification, and outcomes of the
      supraclavicular artery island flap. CONCLUSION: The supraclavicular artery island
      flap is an important and reliable option in head and neck reconstruction. We use
      the flap routinely in our practice as a first-line technique when fasciocutaneous
      soft-tissue reconstruction is required, and we provide a detailed summary of the
      flap elevation and inset. IMPLICATIONS FOR PRACTICE: The supraclavicular artery
      island flap is a safe, reliable, technically simple, sensate, thin, pliable
      fasciocutaneous regional flap option that has low morbidity. It provides sensate,
      single-stage reconstruction for a variety of head and neck defects and should be
      considered as a first-line option in head and neck reconstruction.

PMID- 23554116
TI  - Pilot study of dexmedetomidine in promoting patient comfort without airway
      compromise during awake tracheotomy.

PMID- 23554117
TI  - Neuronal activity promotes myelination via a cAMP pathway.
AB  - Neuronal activity promotes myelination in vivo and in vitro. However, the
      molecular events that mediate activity-dependent myelination are not completely
      understood. Seven, daily 1 h sessions of patterned electrical stimulation (ESTIM)
      promoted myelin segment formation in mixed cultures of dorsal root ganglion (DRG)
      neurons and oligodendrocytes (OLs); the increase in myelination was frequency
      dependent. Myelin segment formation was also enhanced following exposure of DRGs
      to ESTIM prior to OL addition, suggesting that ESTIM promotes myelination in a
      manner involving neuron-specific signaling. Cyclic adenosine monophosphate (cAMP)
      levels in DRGs were increased three-fold following ESTIM, and artificially
      increasing cAMP mimicked the ability of ESTIM to promote myelination.
      Alternatively, inhibiting the cAMP pathway suppressed ESTIM-induced myelination.
      We used compartmentalized, microfluidic platforms to isolate DRG soma from OLs
      and assessed cell-type specific effects of ESTIM on myelination. A selective
      increase or decrease in DRG cAMP levels resulted in enhanced or suppressed
      myelination, respectively. This work describes a novel role for the cAMP pathway
      in neurons that results in enhanced myelination.

PMID- 23554118
TI  - TGF-beta1 induces a nucleus pulposus-like phenotype in Notch 1 knockdown rabbit
      bone marrow mesenchymal stem cells.
AB  - We have investigated the effects of Notch1 knockdown and treatment with TGF-beta1
      on the regulation of the directional differentiation of mesenchymal stem cells
      (MSCs). MSCs were isolated from the femur bone of New Zealand rabbits and
      purified by using discontinuous gradient density centrifugation. Notch1 siRNAs
      were designed, synthesised and transiently transfected into these MSCs, and
      treated with TGF-beta1. The MSCs were examined for morphology, stained with
      toluidine blue for proteoglycan analysis and gene and protein expression were
      measured with qRT-PCR and Western blotting respectively. They had an ellipse or
      fusiform shape and gathered in nests or swirls after being cultured for 7 days.
      Notch1 expression was knocked down with Notch1 siRNA (the silence rate was 47%; P
      < 0.001). After knockdown and TGF-beta1 treatment, MSCs expressed more
      proteoglycan (P < 0.01), and higher levels of collagen II mRNA and protein than
      control cells (P < 0.001). Thus knockdown of Notch1 expression in MSCs may be
      useful in the treatment of intervertebral disc degeneration.

PMID- 23554119
TI  - Preferential associated anomalies in 818 cases of microtia in South America.
AB  - The etiology of microtia remains unknown in most cases. The identification of
      patterns of associated anomalies (i.e., other anomalies that occur with a given
      congenital anomaly in a higher than expected frequency), is a methodology that
      has been used for research into the etiology of birth defects. We conducted a
      study based on cases of microtia that were diagnosed from more than 5 million
      live (LB)- and stillbirths (SB) examined in hospitals participating in ECLAMC
      (Latin American Collaborative Study of Congenital Malformations) between 1967 and
      2009. We identified 818 LB and SB with microtia and at least one additional non
      related major congenital anomaly (cases) and 15,969 LB and SB with two or more
      unrelated major congenital anomalies except microtia (controls). A logistic
      regression analysis was performed to identify the congenital anomalies
      preferentially associated with microtia. Preferential associations were observed
      for 10 congenital anomalies, most of them in the craniofacial region, including
      facial asymmetry, choanal atresia, and eyelid colobomata. The analysis by type of
      microtia showed that for anomalies such as cleft lip and palate, macrostomia, and
      limb reduction defects, the frequency increased with the severity of the
      microtia. In contrast, for other anomalies the frequency tended to be the same
      across all types of microtia. Based on these results we will integrate data on
      the developmental pathways related to preferentially associated congenital
      anomalies for future studies investigating the etiology of microtia.

PMID- 23554120
TI  - Clinical predictors of post-liver transplant new-onset heart failure.
AB  - Objectives of this study were (1) to evaluate preoperative predictors of systolic
      and diastolic heart failure in patients undergoing liver transplantation (LT) and
      (2) to describe the prognostic implications of systolic and diastolic heart
      failure in these patients. The onset of heart failure after orthotopic LT remains
      poorly understood. Data were obtained for all LT recipients between January 2000
      and December 2010. The primary outcome was post-LT heart failure: systolic
      (ejection fraction <= 50%), diastolic, or mixed heart failure. Patients underwent
      echocardiographic evaluation before and after LT. Pretransplant variables were
      evaluated as predictors of heart failure with Cox proportional hazards model. 970
      LT recipients were followed for 5.3 +/- 3.4 years. Ninety-eight patients (10.1%)
      developed heart failure in the posttransplant period. There were 67 systolic
      (6.9%), 24 diastolic (2.5%), and 7 mixed systolic/diastolic (0.7%) heart
      failures. Etiology was ischemic in 18 (18.4%), tachycardia-induced in 8 (8.2%),
      valvular in 7 (7.1%), alcohol-related in 4 (4.1%), hypertensive heart disease in
      3 (3.1%), and nonischemic in majority of patients (59.2%). Pretransplant grade 3
      diastolic dysfunction, diabetes, hypertension, mean arterial pressure <= 65 mm
      Hg, mean pulmonary artery pressure >= 30 mm Hg, mean pulmonary capillary wedge
      pressure >= 15 mm Hg, hemodialysis, brain natriuretic peptide level and QT
      interval > 450 ms were found to be predictive for the development of new-onset
      systolic heart failure. However beta-blocker use before LT and tacrolimus after
      LT were associated with reduced development of new-onset systolic heart failure.
      In conclusion, pretransplant risk factors, hemodynamic variables, and
      echocardiographic variables are important predictors of post-LT heart failure. In
      patients undergoing LT, postoperative onset of systolic or diastolic heart
      failure was found to be an independent predictor of mortality.

PMID- 23554121
TI  - Placement of Tryton Side Branch Stent only; a new treatment strategy for Medina
      0,0,1 coronary bifurcation lesions.
AB  - OBJECTIVES: We propose a new treatment strategy of Medina 0,0,1 bifurcation
      lesions using a dedicated side branch stent alone (Tryton Side Branch StentTM)
      without additional main branch stenting, with the advantage of an optimal ostial
      side branch coverage without the disadvantage of an excessive amount of metal in
      the main branch. BACKGROUND: Medina 0,0,1 lesions are relatively rare and there
      is no consensus on treatment strategy. Several previous techniques have been
      described, all with considerable disadvantages. METHODS: Between October 2009 and
      November 2011, 12 patients with Medina 0,0,1 lesions treated with Tryton alone
      were included. Clinical outcomes were reported as all-cause mortality, recurrent
      myocardial infarction (MI), target vessel revascularization (TVR), target lesion
      revascularization (TLR), and target vessel failure (TVF; defined as the composite
      of all-cause mortality, MI, and TVR). Procedural success was defined as
      successful stent placement with residual stenosis <30%, postprocedural TIMI 3
      flow, and no in-hospital TVF. RESULTS: Mean age was 64 years. Median side branch
      reference vessel diameter was 2.6 [2.5-3.0] mm (median stenosis 75%). Procedural
      success was 100%. Median clinical follow-up duration was 868 [470-906] days with
      just one of the patients suffering from a late adverse clinical outcome: TLR at
      427 days, resulting in TVF, TVR, and TLR rates of 8.3%. CONCLUSION: Treatment of
      Medina 0,0,1 lesions with the Tryton stent alone was associated with a 100%
      procedural success and only one late clinical adverse event (median follow-up of
      868 days). These first positive results need to be confirmed in larger
      prospective randomized studies.

PMID- 23554124
TI  - Abstracts from the 34th Annual Meeting of the American Society for Apheresis, May
      22-25, 2013, Denver, Colorado.

PMID- 23554123
TI  - Proteomic analysis reveals that CD147/EMMPRIN confers chemoresistance in cancer
      stem cell-like cells.
AB  - Cancer stem cells (CSCs) are a subpopulation of tumor cells that can self-renew,
      metastasize, and promote cancer recurrence. A comprehensive characterization of
      the CSC proteome has been hampered due to their scarcity and rapid
      differentiation. Here, we present a systematic analysis of the cell-surface
      proteome using a CSC-like cell line derived from MDA-MB453 breast cancer cells,
      which exhibited a CD44(+) /CD24(-) (where CD is cluster of differentiation)
      phenotype and chemoresistance. We identified differentially expressed proteins in
      CSC-like cells, including upregulated plasma membrane proteins such as CD44,
      CD133, epidermal growth factor receptor (EGFR), CD147, cadherin 1, integrins, and
      catenin (cadherin-associated protein), beta 1 (CTNNB1), using an in-situ
      biotinylation approach followed by MS analysis. We examined the role of CD147 in
      the promotion of CSC growth and survival, and demonstrated that inhibition of
      CD147 with a monoclonal antibody induced significant inhibition of cell growth.
      siRNA-mediated silencing of CD147 gene expression restored the sensitivity of CSC
      like cells to 5-fluorouracil (5-FU), along with decreasing the expression of
      thymidylate synthase, p-AKT, and beta-catenin, while increasing the expression of
      p-glycogen synthase kinase (GSK)3beta. Increased CD147 expression in the CSC-like
      cells, as seen by proteomic analysis, and the functional consequences of CD147
      overexpression in CSC-like cells suggest that CD147 may be one of the critical
      cell-surface proteins involved in promoting chemoresistance and survival in CSCs.

PMID- 23554122
TI  - Design features of implants for direct skeletal attachment of limb prostheses.
AB  - In direct skeletal attachment (DSA) of limb prostheses, a construct is implanted
      into an amputee's residuum bone and protrudes out of the residuum's skin. This
      technology represents an alternative to traditional suspension of prostheses via
      various socket systems, with clear indications when the sockets cannot be
      properly fitted. Contemporary DSA was invented in the 1990s, and several implant
      systems have been introduced since then. The current review is intended to
      compare the design features of implants for DSA whose use in humans or in animal
      studies has been reported in the literature.

PMID- 23554125
TI  - Tungsten-based catalysts for selective deoxygenation.

PMID- 23554126
TI  - Total synthesis and biological evaluation of (+)-gambieric acid A and its
      analogues.
AB  - In this study, we report the first total synthesis and complete stereostructure
      of gambieric acid A, a potent antifungal polycyclic ether metabolite, in detail.
      The A/B-ring exocyclic enol ether 32 was prepared through a Suzuki-Miyaura
      coupling of the B-ring vinyl iodide 18 and the alkylborate 33 and subsequent
      closure of the A-ring by using diastereoselective bromoetherification as the key
      transformation. Suzuki-Miyaura coupling of 32 with acetate-derived enol phosphate
      49, followed by ring-closing metathesis of the derived diene, produced the D
      ring. Subsequent closure of the C-ring through a mixed thioacetalization
      completed the synthesis of the A/BCD-ring fragment 8. The A/BCD- and F'GHIJ-ring
      fragments (i.e., 8 and 9) were assembled through Suzuki-Miyaura coupling. The C25
      stereogenic center was elaborated by exploiting the intrinsic conformational
      property of the seven-membered F'-ring. After the oxidative cleavage of the F'
      ring, the E-ring was formed as a cyclic mixed thioacetal (i.e., 70) and then
      stereoselectively allylated by using glycosylation chemistry. Ring-closing
      metathesis of the diene 3 thus obtained closed the F-ring and completed the
      polycyclic ether skeleton. Finally, the J-ring side chain was introduced by using
      a Julia-Kocienski olefination in the presence of CeCl3 to complete the total
      synthesis of gambieric acid A (1), thereby unambiguously establishing its
      complete stereostructure. The present total synthesis enabled us to evaluate the
      antifungal and antiproliferative activities of 1 and several synthetic analogues.

PMID- 23554127
TI  - Organic electronics.

PMID- 23554128
TI  - Homer proteins in Ca2+ entry.
AB  - The Homer family of proteins consists of three adaptor proteins, Homer1, Homer2
      and Homer3, each with various isoforms. Homer1 family presents an EVH1 domain, a
      coiled coil domain and two leucine zipper domains. Homer proteins regulate a
      number of Ca2+-handling proteins, including transient receptor potential channels
      and other Ca2+-permeable channels, ionotropic and metabotropic glutamate
      receptors, shank scaffolding proteins or endoplasmic reticulum Ca2+ release
      channels. This review article focuses on the association of Homer 1 proteins with
      Ca2+-handling proteins and their role on intracellular Ca2+-homeostasis.

PMID- 23554129
TI  - Cancer of the head and neck region in solid organ transplant recipients.
AB  - BACKGROUND: Solid organ recipients are at an increased risk of developing various
      malignancies. We investigated the incidence, clinical features, and outcome of
      patients diagnosed with head and neck cancer after organ transplantation.
      METHODS: A retrospective analysis was undertaken of patients who underwent solid
      organ transplantation (kidney, liver, lung, heart) treated at our institution
      from 1992 to 2010. RESULTS: Of 2817 organ recipients, 175 patients (6.1%)
      developed 391 head and neck malignancies. Cutaneous malignancies were the most
      common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC;
      42%). The average interval from transplantation to diagnosis of head and neck
      malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen
      percent of patients presented with an aggressive pattern of head and neck cancer,
      including 24% of patients with cutaneous SCC. CONCLUSION: Organ transplantation
      recipients are at a higher risk to develop head and neck cancer with an
      aggressive behavior characterized by multiple recurrences and decreased survival.

PMID- 23554131
TI  - The role of social networking sites in medical genetics research.
AB  - Social networking sites (SNS) have potential value in the field of medical
      genetics as a means of research subject recruitment and source of data. This
      article examines the current role of SNS in medical genetics research and
      potential applications for these sites in future studies. Facebook is the primary
      SNS considered, given the prevalence of its use in the United States and role in
      a small but growing number of studies. To date, utilization of SNS in medical
      genetics research has been primarily limited to three studies that recruited
      subjects from populations of Facebook users [McGuire et al. (2009); Am J Bioeth
      9: 3-10; Janvier et al. (2012); Pediatrics 130: 293-298; Leighton et al. (2012);
      Public Health Genomics 15: 11-21]. These studies and a number of other medical
      and public health studies that have used Facebook as a context for recruiting
      research subjects are discussed. Approaches for Facebook-based subject
      recruitment are identified, including paid Facebook advertising, snowball
      sampling, targeted searching and posting. The use of these methods in medical
      genetics research has the potential to facilitate cost-effective research on both
      large, heterogeneous populations and small, hard-to-access sub-populations.

PMID- 23554130
TI  - Human breast tissue disposition and bioactivity of limonene in women with early
      stage breast cancer.
AB  - Limonene is a bioactive food component found in citrus peel oil that has shown
      chemopreventive and chemotherapeutic activities in preclinical studies. We
      conducted an open-label pilot clinical study to determine the human breast tissue
      disposition of limonene and its associated bioactivity. We recruited 43 women
      with newly diagnosed operable breast cancer electing to undergo surgical excision
      to take 2 grams of limonene daily for two to six weeks before surgery. Blood and
      breast tissue were collected to determine drug/metabolite concentrations and
      limonene-induced changes in systemic and tissue biomarkers of breast cancer risk
      or carcinogenesis. Limonene was found to preferentially concentrate in the breast
      tissue, reaching high tissue concentration (mean = 41.3 MUg/g tissue), whereas
      the major active circulating metabolite, perillic acid, did not concentrate in
      the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1
      expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and
      cleaved caspase-3 expression. No significant changes in serum leptin,
      adiponectin, TGF-beta1, insulin-like growth factor binding protein-3 (IGFBP-3),
      and interleukin-6 (IL-6) levels were observed following limonene intervention.
      There was a small but statistically significant postintervention increase in
      insulin-like growth factor I (IGF-I) levels. We conclude that limonene
      distributed extensively to human breast tissue and reduced breast tumor cyclin D1
      expression that may lead to cell-cycle arrest and reduced cell proliferation.
      Furthermore, placebo-controlled clinical trials and translational research are
      warranted to establish limonene's role for breast cancer prevention or treatment.

PMID- 23554132
TI  - Bioactive substrates for human retinal pigment epithelial cell growth from
      elastin-like recombinamers.
AB  - The aim of this study was to investigate the use of bioactive RGD-containing
      elastin-like recombinamers (ELR-RGDs) as a substrate that can maintain human
      retinal pigment epithelial cell (hRPE) phenotype and growth pattern. Results
      obtained are compared with previously published behavior of ARPE19 cells. The
      extension of these results to hRPE is required because ARPE19 cells cannot be
      used clinically to treat age-related macular degeneration. hRPE cells were
      isolated, cultured, seeded, and grown on surface of glass, treated polystyrene
      (TCP), and solvent-cast ELR-RGD and ELR-IK film with no specific sequence. Cells
      were analyzed to study cell adhesion, proliferation, morphology, and RPE65
      protein expression by staining with diamidino-2-phenylindole, Rhodamine
      Phalloidin, and anti-RPE65 antibody at 12, 24, 72, 120, 168, and 360 h. hRPE
      cells always grew better on ELR-RGD than on glass and ELR-IK but not on TCP. The
      kinetic hRPE growth curves confirmed that growth differences started to appear at
      24 h for these surfaces in ascending order of cell growths, namely glass, ELR-IK,
      ELR-RGD, and TCP. There was a clear difference at 360 h. ELR-RGD maintained hRPE
      cells stable morphology and RPE65 protein expression. ELR-RGD seems to be a good
      substrate for growing hRPE cells with stable morphology and RPE65 protein
      expression. As such, this work confirms our hypothesis regarding ELR-RGD
      substrates viability, which can be used as a Bruch's membrane prosthesis for
      further studies in animals. However, these results must subsequently be
      extrapolated to use of hRPE cells in animals to evaluate them as a
      transplantation vehicle in human.

PMID- 23554134
TI  - Childhood maltreatment and response to cognitive behavioral therapy among
      individuals with social anxiety disorder.
AB  - BACKGROUND: The association between childhood maltreatment-particularly emotional
      maltreatment-and social anxiety disorder (SAD) has been established by research.
      Only recently have researchers begun to look at the impact of childhood
      maltreatment on treatment outcomes, and findings have been mixed. Because prior
      studies have focused on pharmacotherapy outcomes, or used global measures of
      childhood adversity or abuse, it is not clear how specific types of maltreatment
      impact outcomes in cognitive-behavioral therapy (CBT) for SAD. The current study
      reports on how specific types of childhood maltreatment such as physical abuse,
      emotional abuse, sexual abuse, physical neglect, and emotional neglect impact
      response to CBT in adults with SAD. METHODS: Sixty-eight individuals with a
      primary diagnosis of SAD completed the childhood trauma questionnaire, along with
      measures of social anxiety, disability, and life satisfaction. RESULTS: Childhood
      maltreatment did not affect the rate of response to CBT, but there is evidence
      for its negative impact. Patients with histories of emotional abuse and emotional
      neglect reported greater social anxiety, less satisfaction, and greater
      disability over the course of treatment. Sexual abuse also predicted greater
      social anxiety. CONCLUSIONS: Childhood abuse and/or neglect did not result in
      differential rates of improvement during CBT; however, those reporting histories
      of emotional and sexual forms of maltreatment evidenced greater symptoms and/or
      impairment at pre- and posttreatment. Additional attention to the role of
      traumatic experiences within CBT for SAD may be warranted.

PMID- 23554133
TI  - African ancestry is a risk factor for asthma and high total IgE levels in African
      admixed populations.
AB  - Characterization of genetic admixture of populations in the Americas and the
      Caribbean is of interest for anthropological, epidemiological, and historical
      reasons. Asthma has a higher prevalence and is more severe in populations with a
      high African component. Association of African ancestry with asthma has been
      demonstrated. We estimated admixture proportions of samples from six trihybrid
      populations of African descent and determined the relationship between African
      ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry
      informative markers in asthmatics and nonasthmatic controls from Barbados
      (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African
      Americans from New York (207/171), and African Americans from
      Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and
      evaluated genetic stratification using Structure and principal component
      analysis. Association of African ancestry and asthma and tIgE was evaluated by
      regression analysis. Mean +/- SD African ancestry ranged from 0.76 +/- 0.10 among
      Barbadians to 0.33 +/- 0.13 in Colombians. The European component varied from
      0.14 +/- 0.05 among Jamaicans and Barbadians to 0.26 +/- 0.08 among Colombians.
      African ancestry was associated with risk for asthma in Colombians (odds ratio
      (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans
      of New York (OR: 4.7; P = 0.040). African ancestry was also associated with
      higher tIgE levels among Colombians (beta = 1.3, P = 0.04), Barbadians (beta =
      3.8, P = 0.03), and Brazilians (beta = 1.6, P = 0.03). Our findings indicate that
      African ancestry can account for, at least in part, the association between
      asthma and its associated trait, tIgE levels.

PMID- 23554135
TI  - Overcoming neurite-inhibitory chondroitin sulfate proteoglycans in the astrocyte
      matrix.
AB  - Acute trauma to the central nervous system (CNS) can result in permanent damage
      and loss of function related to the poor regeneration of injured axons. Injured
      axons encounter several barriers to regeneration, such as the glial scar at the
      injury site. The glial scar contains extracellular matrix (ECM) macromolecules
      deposited by reactive astrocytes in response to injury. The scar ECM is rich in
      chondroitin sulfate proteoglycans (CSPGs), macromolecules that inhibit axonal
      growth. CSPGs consist of a core protein with attachment sites for
      glycosaminoglycan (GAG) chains. An extensive literature demonstrates that
      enzymatic removal of the GAG chains by chondroitinase ABC permits some axonal
      regrowth; however, the remaining intact core proteins also possess inhibitory
      domains. Because metalloproteinases can degrade core proteins of CSPGs, we have
      evaluated five matrix metalloproteinases (MMPs) and a related protease-a
      disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)-for
      their capacity to overcome CSPG inhibition of neuritic growth in culture. The
      metalloproteinases were selected for their known expression after CNS injuries.
      Of the MMPs, MMP-3, -7 and -8 reduced or abolished inhibition of neurite
      outgrowth on a purified CSPG substrate and on an astrocyte-derived ECM. ADAMTS-4
      also attenuated CSPG inhibition of neurites and had the additional benefits of
      neither degrading laminin nor causing neurotoxicity. The efficacy of ADAMTS-4
      matched that of blocking the EGFR signaling previously reported to mediate CSPG
      inhibition. These findings highlight ADAMTS-4 as a superior protease for
      overcoming CSPG inhibition of axonal regeneration in the CNS.

PMID- 23554136
TI  - Yerba mate tea and mate saponins prevented azoxymethane-induced inflammation of
      rat colon through suppression of NF-kappaB p65ser(311) signaling via IkappaB
      alpha and GSK-3beta reduced phosphorylation.
AB  - Yerba mate tea (YMT) has a chemopreventive role in a variety of inflammatory
      diseases. The objective was to determine the capability of YMT and mate saponins
      to prevent azoxymethane (AOM)-induced colonic inflammation in rats. YMT (2% dry
      leaves, w/v, as a source of drinking fluid) (n = 15) and mate saponins (0.01% in
      the diet, at a concentration present in one cup of YMT) (n = 15) were given ad
      libitum to rats 2 weeks prior to AOM-injection until the end of the study; while
      control rats (n = 15) received a basal diet and drinking water. After 8-weeks of
      study, total colonic mucosa was scraped (n = 3 rats/group) and the remaining
      colons (n =12 rats/group) were cut into three equal sections and aberrant crypt
      foci (ACF) were analyzed. YMT reduced ACF formation from 113 (control group) to
      89 (P < 0.05). YMT and mate saponins reduced the expression of proinflammatory
      molecules COX-2 and iNOS with concomitant reduction in p-p65 (P < 0.05).
      Immunohistochemical analysis of the formalin-fixed middle colons showed that YMT
      and mate saponins reduced the expression of p-p65(ser311) by 45.7% and 43.1%,
      respectively, in comparison to the control (P < 0.05). In addition, the
      expression of molecules upstream of NF-kappaB such as p-IkappaB-alpha and p-GSK
      3beta(Y216) was downregulated by YMT 24.7% and 24.4%, respectively (P < 0.05).
      Results suggest the mechanism involved in the chemopreventive effect of YMT and
      mate saponin consumption in AOM induced-colonic inflammation in rats is through
      inhibition of NF-kappaB.

PMID- 23554137
TI  - Bilateral pallidal stimulation for Wilson's disease.
AB  - BACKGROUND: To report on the clinical efficacy of bilateral globus pallidus
      internus deep brain stimulation in a 29-year-old patient with severe generalized
      dystonia secondary to Wilson's disease. METHODS: The primary outcome measure was
      the Burke-Fahn-Marsden Dystonia Scale motor severity score (blinded assessment)
      and the secondary outcome measures were the Abnormal Involuntary Movement Scale
      (blinded assessment) and the Zaritt Caregiver Burden Interview score, at 20-week
      postoperative follow up. RESULTS: There was a 14% improvement in the Burke-Fahn
      Marsden Dystonia Scale motor severity score. Abnormal Involuntary Movement Scale
      score remained unchanged while the Zaritt Caregiver Burden Interview score
      improved by 44.4%. CONCLUSIONS: Bilateral globus pallidus deep brain stimulation
      can be effective in ameliorating dystonia and caregiver burden in Wilson's
      disease. Outcomes may depend on the stage of the disease at which the surgical
      procedure is completed. (c) 2013 Movement Disorder Society.

PMID- 23554138
TI  - Cu2(OH)PO4, a near-infrared-activated photocatalyst.

PMID- 23554139
TI  - Randomized controlled trial of physiotherapy for postpartum stress incontinence:
      7-year follow-up.
AB  - OBJECTIVE: To estimate the long-term effect of intensive, 6-week physiotherapy
      programs, with and without deep abdominal muscle (TrA) training, on persistent
      postpartum stress urinary incontinence (SUI). METHODS: The study was a single
      blind randomized controlled trial. Fifty-seven postnatal women with clinically
      demonstrated persistent SUI 3 months after delivery participated in 8 weeks of
      either pelvic floor muscle training (PFMT) (28) or PFMT with deep abdominal
      muscle training (PFMT + TrA) (29). Seven years post-treatment, 35 (61.4%)
      participants agreed to the follow-up; they were asked to complete a 20-min pad
      test and three incontinence-specific questionnaires with an assessor blinded to
      each participant's group assignment. RESULTS: Of the 35 (61.4%) who agreed to the
      follow-up: 26 (45.6%) took the 20-min pad test (12 PFMT and 14 PFMT + TrA) and 35
      (61.4%) completed the questionnaires (18 PFMT and 17 PFMT + TrA). The baseline
      clinical characteristics of the follow-up and non-follow-up participants were not
      significantly different; nor did they differ between PFMT and PFMT + TrA
      participants enrolled in the follow-up study. At 7 years, the pad test scores for
      the PFMT group did not differ statistically from those of the PFMT + TrA group.
      When combining both treatment groups, a total of 14/26 (53%) follow-up
      participants were still continent according to the pad test. CONCLUSION: The
      addition of deep abdominal training does not appear to further improve the
      outcome of PFM training in the long term. However, benefits of physiotherapy for
      postpartum SUI, although not as pronounced as immediately after the initial
      intervention, is still present 7 years post-treatment.

PMID- 23554140
TI  - SiCN nanofibers with a diameter below 100 nm synthesized via concerted block
      copolymer formation, microphase separation, and crosslinking.
AB  - SiCN fibers with a mean diameter of 50 nm and an aspect ratio of up to 100 are
      produced in a two-step process by R. Kempe and co-workers. The key step to
      fabricate the longitudinal and cross-sectional views of the mesofibers shown here
      is a concerted block-copolymer synthesis, microphase separation, and cross
      linking at 140  degrees C followed by pyrolysis at 1100  degrees C. Inexpensive
      components like a commercially available silazane and polyethylene are linked.
      The fibers may find application in electronic devices, as components of ceramic
      matrix composites, as fiber beds in high-temperature nano-filtering like diesel
      fine dust removal, or as thermally robust and chemically inert catalyst supports.
      Furthermore, the SiCN nanofibers introduced on page 984 are a promising
      alternative to ultrathin carbon fibers, due to their oxidation resistance.

PMID- 23554141
TI  - Potential of co-culture of nucleus pulposus mesenchymal stem cells and nucleus
      pulposus cells in hyperosmotic microenvironment for intervertebral disc
      regeneration.
AB  - Nucleus pulposus mesenchymal stem cells (NPMSCs) are a potential cell source for
      intervertebral disc (IVD) regeneration, but little is known about their response
      to IVD-like high osmolarity (400 mOsm). This study was to investigate the
      viability, proliferation and protein biosynthesis of nucleus pulposus cells
      (NPCs), NPMSCs and co-cultured NPMSCs-NPCs under IVD-like high osmolarity
      conditions. NPCs and NPMSCs were isolated and cultured under standard and IVD
      like high osmolarity conditions for 1 or 2 weeks. Cell viability was measured by
      annexin V-FITC and PI staining, and cell proliferation measured by MTT assay. The
      expression of SOX-9, aggrecan and collagen-II was measured by RT-PCR and Western
      blot analyses. IVD-like high osmolarity condition slightly inhibited cell
      viability and decreased the expression of SOX-9, aggrecan and collagen-II at the
      mRNA and protein levels in all groups compared with standard condition. NPMSCs
      could tolerate IVD-like high osmolarity, and NPCs-NPMSCs co-culture increased
      cell proliferation and the expression of SOX-9, aggrecan and collagen-II under
      both culture conditions, suggesting that co-culture of NPMSCs-NPCs has potential
      application for IVD regeneration.

PMID- 23554142
TI  - Role of toll-like receptor 4 in mediating multiorgan dysfunction in mice with
      acetaminophen induced acute liver failure.
AB  - Strategies for the prevention of multiorgan dysfunction (MOD) in acetaminophen
      (APAP)-induced acute liver failure (ALF) are an unmet need. Our study tested the
      hypothesis that sterile inflammation induced by APAP in a mouse model would
      activate toll-like receptor 4 (TLR4) in the liver and extrahepatic organs and
      lead to the progression of ALF and MOD and that the administration of the novel
      TLR4 antagonist STM28 (a peptide formed of 17 amino-acids) would prevent liver
      injury and associated MOD. ALF and, subsequently, MOD were induced in TLR4
      knockout (KO) mice (B6.B10ScN-Tlr4 (lpsdel) /JthJ) and wild-type (WT) mice
      (C57BL/6) with APAP (500 mg/kg). A second set of experiments was conducted to
      evaluate the effects of a pretreatment with a novel TLR4 antagonist, STM28, on
      APAP-induced MOD in CD1 mice. Animals were sacrificed at the coma stage, and
      plasma, peripheral blood cells, liver, kidneys, and brain were collected.
      Biochemistry values and cytokines were measured. Liver and kidneys were studied
      histologically and were stained for TLR4 and activated Kupffer cells, and the
      expression of nuclear factor kappa B-p65 was quantified with western blotting.
      Brain water was measured in the frontal cortex. After APAP administration, TLR4
      KO (NFkBp65) mice were relatively protected from liver necrosis and end-organ
      dysfunction and had significantly better survival than WT controls (P < 0.01).
      STM28 attenuated liver injury and necrosis, reduced creatinine levels, and
      delayed the time to a coma significantly. The increases in cytokines in the
      plasma and liver, including TLR4 expression and the activation of Kupffer cells,
      after APAP administration were reduced significantly in the STM28-treated
      animals. The increased number of circulating myeloid cells was reduced
      significantly after STM28 treatment. In conclusion, these data provide evidence
      for an important role of the TLR4 antagonist in the prevention of the progression
      of APAP-induced ALF and MOD.

PMID- 23554143
TI  - Multiplex epitope detection: a new method overcomes limitations of antibody
      arrays.
AB  - Antibody arrays have been used as an effective method for simultaneously
      detecting multiple proteins such as cytokines. However, their use in quantifying
      a large number of cellular proteins has the following limitations: (i) unsuitable
      for simultaneously detecting proteins that may form complexes with each other;
      (ii) incapable of quantitatively detecting more than one epitope of each protein
      such as phospho- and nonphospho-epitopes; and (iii) incapable of simultaneously
      detecting multiple biomarkers on solid surfaces such as formalin-fixed tissue
      sections. Using a novel multiple epitope detection (MED) technique, we have
      overcome these limitations and have improved upon currently available antibody
      based protein detection technologies. The MED technique employs primary antibody
      detection of epitopes within fixed cells or tissue, followed by elution of bound
      antibodies, and subsequent quantification of the eluted antibodies by an epitope
      array. Using the MED method, we demonstrate accurate detection of individual
      proteins even in complex with each other, simultaneous quantitative detection of
      phospho- and nonphospho-epitopes on a protein, and sensitive detection of
      multiple biomarkers on formalin-fixed tissue sections.

PMID- 23554144
TI  - Winner for outstanding research in the Ph.D. category for the 2013 Society for
      Biomaterials meeting and exposition, April 10-13, 2013, Boston, Massachusetts:
      Osteogenic differentiation of adipose-derived and marrow-derived mesenchymal stem
      cells in modular protein/ceramic microbeads.
AB  - Modular tissue engineering applies biomaterials-based approaches to create
      discrete cell-seeded microenvironments, which can be further assembled into
      larger constructs for the repair of injured tissues. In the current study, we
      embedded human bone marrow-derived mesenchymal stem cells (MSC) and human adipose
      derived stem cells (ASC) in collagen/fibrin (COL/FIB) and
      collagen/fibrin/hydroxyapatite (COL/FIB/HA) microbeads, and evaluated their
      suitability for bone tissue engineering applications. Microbeads were fabricated
      using a water-in-oil emulsification process, resulting in an average microbead
      diameter of approximately 130 +/- 25 MUm. Microbeads supported both cell
      viability and cell spreading of MSC and ASC over 7 days in culture. The embedded
      cells also began to remodel and compact the microbead matrix as demonstrated by
      confocal reflectance microscopy imaging. After two weeks of culture in media
      containing osteogenic supplements, both MSC and ASC deposited calcium mineral in
      COL/FIB microbeads, but not in COL/FIB/HA microbeads. There were no significant
      differences between MSC and ASC in any of the assays examined, suggesting that
      either cell type may be an appropriate cell source for orthopedic applications.
      This study has implications in the creation of defined microenvironments for bone
      repair, and in developing a modular approach for delivery of pre-differentiated
      cells.

PMID- 23554145
TI  - Differences in recovery of left and right ventricular function following aortic
      valve interventions: a longitudinal echocardiographic study in patients
      undergoing surgical, transapical or transfemoral aortic valve implantation.
AB  - OBJECTIVES: To evaluate longitudinal left and right ventricular function (LVF and
      RVF) after transcatheter aortic valve implantation (TAVI) as compared to surgical
      aortic valve replacement (SAVR) and LVF and RVF after TAVI by the transfemoral
      (TF) or transapical (TA) approach. BACKGROUND: Knowledge about differences in
      recovery of LVF and RVF after TAVI and SAVR is scarce. METHODS: Sixty patients
      (age 81 +/- 7 years, logistic EuroSCORE 16 +/- 10%), undergoing TAVI (TF: n = 35
      and TA: n = 25), were examined by echocardiography including atrioventricular
      plane displacement (AVPD) and peak systolic velocities (PSV) by tissue Doppler at
      basal RV free wall, LV lateral wall and septum preprocedurally, 7 weeks and 6
      months postprocedurally. Twenty-seven SAVR patients were matched to 27 TAVI
      patients by age, gender and LVF. RESULTS: Early postintervention, TAVI patients
      had improved longitudinal LVF. However, when analyzed separately, only TF, but
      not TA patients, had improved LV lateral and septal AVPD and PSV (all P <= 0.01).
      All TAVI patients, as well as the TF and TA group had unchanged longitudinal LVF
      between the early and late follow-ups (all P > 0.05). The SAVR group had higher
      septal LVF than the matched TAVI group preprocedurally, while postoperatively
      this difference was diminished. Longitudinal RVF was better in the TF group than
      in the TA group pre- and postprocedurally. Although the SAVR group had superior
      longitudinal RVF preoperatively, this was inferior to TAVI postoperatively.
      CONCLUSIONS: Postprocedural longitudinal LVF and RVF in patients undergoing TF
      TAVI, TA-TAVI, or SAVR differ considerably. Preservation of longitudinal RVF
      after TAVI might influence the selection of aortic valve intervention in the
      future.

PMID- 23554147
TI  - Redox chain reaction-indole and pyrrole alkylation with unactivated secondary
      alcohols.
AB  - Secondary role: Indole and pyrrole derivatives are alkylated with unactivated
      secondary aliphatic alcohols by a Bronsted acid-catalyzed redox chain reaction
      mechanism. Broad functional-group tolerance has been demonstrated and preliminary
      studies suggest that 1,4-reduction of a putative indolyl carbocation is the
      dominant mechanistic pathway.

PMID- 23554148
TI  - Sexually dimorphic expression and estradiol mediated up-regulation of a sex
      linked ribosomal gene, RPS6, in the zebra finch brain.
AB  - Sex-linked genes are considered to be a major contributor to neural sex
      differences in zebra finches. While several candidates have been identified,
      additional ones are continuously being discovered. Here we report on a novel Z
      linked ribosomal gene (rpS6) that is enhanced in the male brain as compared to
      the female's throughout life. In both sexes, expression of rpS6 is highest at P3
      and P8 (just before the onset of morphologically detectable sex differences),
      decreases around P15, and then remains decreased through adulthood. Analysis of
      rpS6 mRNA revealed widespread distribution throughout the brain. However, within
      song regions HVC and RA, mRNA containing cells were greater in males as compared
      to females. Hormones are also involved in the development of neural dimorphisms,
      so we additionally investigated whether rpS6 might interact with estradiol (E2 ).
      An up-regulation of rpS6 gene was observed in both sexes following treatment with
      E2 and the effect was approximately twice as large in males as compared with
      females. These data suggest that rpS6 may be involved in sexual differentiation
      of the zebra finch brain, and that the effect is facilitated by E2 .

PMID- 23554149
TI  - Elastic fibers in elastofibroma dorsi by fine-needle aspiration.
AB  - Fine-needle aspiration (FNA) features of elastofibroma dorsi (EFD) in a 56-year
      old woman were evaluated. The patient presented with 5 cm soft tissue mass
      located between the inferior part of scapula and the chest wall. FNA smears were
      hypercellular, characterized by a mixture of uniform spindle cells, mature
      adipocytes, and collagen tissue fragments in varying proportions. The cytological
      findings included abundant degenerated elastic fibers presented as linear ("braid
      like") and globular bodies with shell-like and stellate appearances with serrate
      borders, permitting a diagnosis of EFD. Occurrence of degenerated elastic fibers
      in FNA smears of elastofibroma is a highly diagnostic sign in the typical
      clinical setting and eliminates the need for preoperative histological
      examination.

PMID- 23554151
TI  - NIR photoresponsive crosslinked upconverting nanocarriers toward selective
      intracellular drug release.
AB  - An NIR-responsive mesoporous silica coated upconverting nanoparticle (UCNP)
      conjugate is developed for controllable drug delivery and fluorescence imaging in
      living cells. In this work, antitumor drug doxorubicin (Dox) molecules are
      encapsulated within cross-linked photocaged mesoporous silica coated UCNPs. Upon
      980 nm light irradiation, Dox could be selectively released through the
      photocleavage of theo-nitrobenzyl (NB) caged linker by the converted UV emission
      from UCNPs. This NIR light-responsive nanoparticle conjugate demonstrates high
      efficiency for the controlled release of the drug in cancer cells. Upon
      functionalization of the nanocarrier with folic acid (FA), this photocaged FA
      conjugated silica-UCNP nanocarrier will also allow targeted intracellular drug
      delivery and selective fluorescence imaging towards the cell lines with high
      level expression of folate receptor (FR). 

PMID- 23554152
TI  - DNA patchy particles.
AB  - A simple and effective way to make DNA patchy particles is reported. A small
      patch of DNA strands is "stamped" from a gold surface onto colloidal particles of
      different sizes by streptavidin-biotin bonds. These DNA patchy particles provide
      direction-selective and thermoreversible interactions, and hence can lead to
      unique assembly protocols and structures controlled by temperature.

PMID- 23554153
TI  - Biomechanical deviations during level walking associated with knee
      osteoarthritis: a systematic review and meta-analysis.
AB  - OBJECTIVE: To identify which gait deviations are consistently associated with
      knee osteoarthritis (KOA) and how these are influenced by disease severity, the
      involved compartment, and sex. METHODS: Five electronic databases and reference
      lists of publications were searched. Cross-sectional, observational studies
      comparing temporospatial variables, joint kinematics, and joint moments between
      individuals with KOA and healthy controls or between KOA subgroups were
      considered for review. Only publications scoring >=50% on a modified methodology
      quality index were included. Because of the number of gait deviations examined,
      only biomechanical variables reported by >=4 publications were further analyzed.
      Where possible, a meta-analysis was performed using effect sizes (ES) calculated
      from discrete variables. RESULTS: In total, 41 publications examining 20
      variables were included. The majority of consistent gait deviations associated
      with KOA were exhibited by those with severe disease in the temporospatial
      domain. Individuals with severe KOA exhibited greater stride duration than
      controls (ES 1.35 [95% confidence interval (95% CI) 1.03, 1.67]) and a decrease
      in cadence (ES -0.75 [95% CI -1.12, -0.39]) compared with controls. The evidence
      for kinematic and joint moment change was primarily limited or conflicting. There
      was a lack of evidence for alterations in the external knee adduction moment.
      CONCLUSION: Individuals with KOA exhibit a range of gait deviations compared with
      controls. Despite its common usage in KOA gait studies, we did not find
      consistent evidence that knee adduction moment differs between those with and
      without KOA or between disease severity levels. Further research examining the
      reasons for a lack of difference in many gait variables in those with knee OA is
      needed.

PMID- 23554154
TI  - Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair.
AB  - A nerve conduit is designed to improve peripheral nerve regeneration by providing
      guidance to the nerve cells. Conductivity of such guides is reported to enhance
      this process. In the current study, a nerve guide was constructed from poly(2
      hydroxyethyl methacrylate) (pHEMA), which was loaded with multiwalled carbon
      nanotubes (mwCNT) to introduce conductivity. PHEMA hydrogels were designed to
      have a porous structure to facilitate the transportation of the compounds needed
      for cell nutrition and growth and also for waste removal. We showed that when
      loaded with relatively high concentrations of mwCNTs (6%, w/w in hydrogels), the
      pHEMA guide was more conductive and more hydrophobic than pristine pHEMA
      hydrogel. The mechanical properties of the composites were better when they
      carried mwCNT. Elastic modulus of 6% mwCNT loaded pHEMA was twofold higher (0.32
      +/- 0.06 MPa) and similar to that of the soft tissues. Electrical conductivity
      was significantly improved (11.4-fold) from 7 * 10(-3) Omega(-1).cm(-1) (pHEMA)
      to 8.0 * 10(-2) Omega(-1).cm(-1) (6% mwCNT loaded pHEMA). On application of
      electrical potential, the SHSY5Y neuroblastoma cells seeded on mwCNTs carrying
      pHEMA maintained their viability, whereas those on pure pHEMA could not,
      indicating that mwCNT helped conduct electricity and make them more suitable as
      nerve conduits.

PMID- 23554155
TI  - Effects of nicotine withdrawal on panic-like response to breath holding: a
      placebo-controlled, double-blind, crossover patch study.
AB  - BACKGROUND: Cigarette smoking may increase the likelihood of developing panic
      disorder. Periods of nicotine withdrawal, in particular, may promote panic in
      individuals high in anxiety sensitivity. We examined the importance of nicotine
      withdrawal in the occurrence of smoking and panic. METHODS: We utilized a placebo
      controlled, double-blind, randomized, crossover design. Fifty smokers underwent a
      breath-holding (BH) challenge after the transdermal administration of nicotine on
      one test day and a placebo on another test day. Physiological and psychological
      variables were assessed at baseline as well as directly before and after the
      challenges. RESULTS: Nicotine abstinence induced a decrease in heart rate and
      systolic blood pressure (BP) before the BH procedure (heart rate: 78.80 +/- 11.43
      under nicotine, 70.88 +/- 10.83 under placebo; systolic BP: 124.90 +/- 11.34
      under nicotine, 121.18 +/- 13.44 under placebo) and shorter BH duration relative
      to the nicotine patch condition. Nicotine abstinence did not, though, increase
      fear reactivity to the challenge. CONCLUSIONS: The findings for heart rate and BP
      are consistent with the stimulant properties of nicotine. The reduced capacity to
      maintain apnea under placebo might be due to carbon dioxide (CO2 )
      hypersensitivity during periods of nicotine abstinence. The negative findings
      regarding fear reactivity might be due to BH being a relatively weak anxiogen.
      Future researchers are encouraged to employ CO2 -inhalation procedures to study
      the relationship between nicotine withdrawal and panic.

PMID- 23554156
TI  - Multilateral contracting and prevention.
AB  - Incentives created through contracts can be used as a means of decentralized
      control in healthcare systems to ensure more efficient healthcare. In this paper,
      we consider an insurer contracting with a consumer and a provider. We focus on
      the trade-off between ex ante moral hazard and insurance, and consider both
      consumer and provider incentives in the insurer's contracting problem in the
      presence of unobservable preventive efforts. We study two cases of provider
      efforts: those that complement consumer efforts and those that substitute for
      consumer efforts. In the first case, our results show that the provider must have
      greater incentives when the consumer is healthy to induce effort and that
      inducing provider effort allows an insurer to offer a more complete insurance
      contract relative to the bilateral benchmark. In the second case, we state
      conditions under which these conclusions continue to hold. On the basis of our
      findings, we discuss the implications and challenges of multilateral contracting
      in practice.

PMID- 23554157
TI  - Excitation-wavelength-dependent, ultrafast photoinduced electron transfer in
      bisferrocene/BF2-chelated-azadipyrromethene/fullerene tetrads.
AB  - Donor-acceptor distance, orientation, and photoexcitation wavelength are key
      factors in governing the efficiency and mechanism of electron-transfer reactions
      both in natural and synthetic systems. Although distance and orientation effects
      have been successfully demonstrated in simple donor-acceptor dyads, revealing
      excitation-wavelength-dependent photochemical properties demands multimodular,
      photosynthetic-reaction-center model compounds. Here, we successfully demonstrate
      donor- acceptor excitation-wavelength-dependent, ultrafast charge separation and
      charge recombination in newly synthesized, novel tetrads featuring bisferrocene,
      BF2 -chelated azadipyrromethene, and fullerene entities. The tetrads synthesized
      using multistep synthetic procedure revealed characteristic optical, redox, and
      photo reactivities of the individual components and featured "closely" and
      "distantly" positioned donor-acceptor systems. The near-IR-emitting BF2-chelated
      azadipyrromethene acted as a photosensitizing electron acceptor along with
      fullerene, while the ferrocene entities acted as electron donors. Both tetrads
      revealed excitation-wavelength-dependent, photoinduced, electron-transfer events
      as probed by femtosecond transient absorption spectroscopy. That is, formation of
      the Fc(+)-ADP-C60(.-) charge-separated state upon C60 excitation, and Fc(+)-ADP(.
      )-C60 formation upon ADP excitation is demonstrated.

PMID- 23554158
TI  - Enabling in vivo measurements of nanoparticle concentrations with three
      dimensional optoacoustic tomography.
AB  - In this report, we demonstrate the feasibility of using optoacoustic tomography
      (OAT) to evaluate biodistributions of nanoparticles in animal models. The
      redistribution of single-walled carbon nanotubes (SWCNTs) was visualized in
      living mice. Nanoparticle concentrations in harvested organs were measured
      spectroscopically using the intrinsic optical absorption and fluorescence of
      SWCNTs. Observed increases in optoacoustic signal brightness in tissues were
      compared with increases in optical absorption coefficients caused by SWCNT
      accumulation. The methodology presented in this report can further be extended to
      calibrate the sensitivity of an optoacoustic imaging system for a range of
      changes in optical absorption coefficient values at specific locations or organs
      in a mouse body to enable noninvasive measurements of nanoparticle concentrations
      in vivo. Additionally, qualitative information provided by OAT and quantitative
      information obtained ex vivo may provide valuable feedback for advancing methods
      of quantitative analysis with OAT.

PMID- 23554159
TI  - Design of a core classification process for DNA mismatch repair variations of a
      priori unknown functional significance.

PMID- 23554160
TI  - Nrf2-regulated phase-II detoxification enzymes and phase-III transporters are
      induced by thyroid hormone in rat liver.
AB  - Thyroid hormone (T3)-induced calorigenesis triggers the hepatic production of
      reactive oxygen species (ROS) and redox-sensitive nuclear transcription factor
      erythroid 2-related factor 2 (Nrf2) activation. The aim of this study was to test
      the hypothesis that in vivo T3 administration upregulates the expression of phase
      II and III detoxification proteins that is controlled by Nrf2. Male Sprague
      Dawley rats were given a single intraperitoneal dose of 0.1 mg T3/kg or T3
      vehicle (controls). After treatment, rectal temperature of the animals, liver
      Nrf2 DNA binding (EMSA), protein levels of epoxide hydrolase 1 (Eh1), NADPH
      quinone oxidoreductase 1 (NQO1), glutathione-S-transferases Ya (GST Ya) and Yp
      (GST Yp), and multidrug resistance-associated proteins 2 (MRP-2) and 4 (MRP-4)
      (Western blot), and MRP-3 (RT-PCR) were determined at different times. T3
      significantly rose the rectal temperature of the animals in the time period
      studied, concomitantly with increases (P < 0.05) of liver Nrf2 DNA binding at 1
      and 2 h after treatment, which was normalized at 4-12 h. Within 1-2 h after T3
      treatment, liver phase II enzymes Eh1, NQO1, GST Ya, and GST Yp were enhanced (P
      < 0.05) as did phase III transporters MRP-2 and MRP-3, whereas MRP-4 remained
      unchanged. In conclusion, enhancement of liver Nrf2 DNA binding elicited by in
      vivo T3 administration is associated with upregulation of the expression of
      detoxification and drug transport proteins. These changes, in addition to
      antioxidant protein induction previously observed, may represent cytoprotective
      mechanisms underlying T3 preconditioning against liver injury mediated by ROS and
      chemical toxicity.

PMID- 23554162
TI  - Significant expansion of the fluorescent protein chromophore through the genetic
      incorporation of a metal-chelating unnatural amino acid.

PMID- 23554161
TI  - Surface projections of titanium substrates increase antithrombotic endothelial
      function in response to shear stress.
AB  - Despite the therapeutic benefits of both mechanical circulatory assist devices
      and nitinol stents with titanium (Ti) outer surfaces, problems remain with
      thrombosis at the blood-contacting surface. Covering these surfaces with a layer
      of endothelium would mimic the native lining of the cardiovascular system,
      potentially decreasing thrombotic complications. Since surface topography is
      known to affect the phenotype of a seeded cell layer and since stents and
      ventricular assist devices exhibit surface protrusions, we tested the hypothesis
      that endothelial cells (ECs) have altered function on Ti surfaces with
      protrusions of 1.25, 3, and 5 MUm height, compared with smooth Ti surfaces. ECs
      and nuclei were more aligned and ECs were more elongated on all patterned
      surfaces. Cell area was reduced on the 3 and 5 MUm features. Expression of eNOS
      and COX2 was not altered by patterned surfaces, but expression of KLF-2 was
      higher on 1.25 and 5 MUm features. Nitric oxide production following exposure to
      flow was higher on the 5 MUm features. These results show that some
      antithrombogenic functions of ECs are significantly enhanced for ECs cultured on
      surface protrusions, and no functions are diminished, informing the future design
      of implant surfaces for endothelialization.

PMID- 23554163
TI  - A method to detect differentially methylated loci with next-generation
      sequencing.
AB  - Epigenetic changes, especially DNA methylation at CpG loci have important
      implications in cancer and other complex diseases. With the development of next
      generation sequencing (NGS), it is feasible to generate data to interrogate the
      difference in methylation status for genome-wide loci using case-control design.
      However, a proper and efficient statistical test is lacking. There are several
      challenges. First, unlike methylation experiments using microarrays, where there
      is one measure of methylation for one individual at a particular CpG site, here
      we have the counts of methylation allele and unmethylation allele for each
      individual. Second, due to the nature of sample preparation, the measured
      methylation reflects the methylation status of a mixture of cells involved in
      sample preparation. Therefore, the underlying distribution of the measured
      methylation level is unknown, and a robust test is more desirable than parametric
      approach. Third, currently NGS measures methylation at over 2 million CpG sites.
      Any statistical tests have to be computationally efficient in order to be applied
      to the NGS data. Taking these challenges into account, we propose a test for
      differential methylation based on clustered data analysis by modeling the
      methylation counts. We performed simulations to show that it is robust under
      several distributions for the measured methylation levels. It has good power and
      is computationally efficient. Finally, we apply the test to our NGS data on
      chronic lymphocytic leukemia. The results indicate that it is a promising and
      practical test.

PMID- 23554164
TI  - Development of a novel telomerase assay using the PPDK-luciferin-luciferase
      detection system.
AB  - Telomerase participates in malignant transformation or immortalization of cells,
      and has attracted attention as an anticancer drug screening and diagnostic tumor
      marker. We developed a novel telomerase assay called the PPDK-luciferin
      luciferase system bioluminescence assay (PLLBA) using pyruvate phosphate dikinase
      (PPDK). In this assay, pyrophosphate produced by the telomerase reaction and
      polymerase chain reaction (PCR) is converted to ATP by PPDK, and ATP is detected
      by the firefly luciferin-luciferase reaction. In this work, telomerase substrate
      was obtained in accordance with the telomeric repeat amplification protocol
      (TRAP). Telomerase-positive (500 cells/assay), -inactive (heated for 10 min at 85
      degrees C) and -negative (only Chaps lysis buffer) samples were used. As a
      result, the findings clearly showed that the signal-to-noise (S/N) ratio of the
      positive cells was 39.5. After the telomerase reaction and PCR, PLLBA was
      completed ~ 120 s later. A high level of reproducibility was obtained with -
      coefficient of variation (CV) of 4.1% (positive cells). The detection limit for
      cells using telomerase was one cell per assay. This assay for telomerase activity
      was also shown to be adaptable to human cancer-derived cell lines.

PMID- 23554166
TI  - Coping with stress: a challenge for theory, research and practice.

PMID- 23554168
TI  - The use of whole genome sequencing to solve an epidemiological puzzle.

PMID- 23554169
TI  - A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease
      signature, as IL-10 dependent derivatives of inflammatory monocytes.
AB  - Rhinoscleroma is a human specific chronic disease characterized by the formation
      of granuloma in the airways, caused by the bacterium Klebsiella pneumoniae
      subspecies rhinoscleromatis, a species very closely related to K. pneumoniae
      subspecies pneumoniae. It is characterized by the appearance of specific foamy
      macrophages called Mikulicz cells. However, very little is known about the
      pathophysiological processes underlying rhinoscleroma. Herein, we characterized a
      murine model recapitulating the formation of Mikulicz cells in lungs and
      identified them as atypical inflammatory monocytes specifically recruited from
      the bone marrow upon K. rhinoscleromatis infection in a CCR2-independent manner.
      While K. pneumoniae and K. rhinoscleromatis infections induced a classical
      inflammatory reaction, K. rhinoscleromatis infection was characterized by a
      strong production of IL-10 concomitant to the appearance of Mikulicz cells.
      Strikingly, in the absence of IL-10, very few Mikulicz cells were observed,
      confirming a crucial role of IL-10 in the establishment of a proper environment
      leading to the maturation of these atypical monocytes. This is the first
      characterization of the environment leading to Mikulicz cells maturation and
      their identification as inflammatory monocytes.

PMID- 23554170
TI  - Amyloid precursor protein controls cholesterol turnover needed for neuronal
      activity.
AB  - Perturbation of lipid metabolism favours progression of Alzheimer disease, in
      which processing of Amyloid Precursor Protein (APP) has important implications.
      APP cleavage is tightly regulated by cholesterol and APP fragments regulate lipid
      homeostasis. Here, we investigated whether up or down regulation of full-length
      APP expression affected neuronal lipid metabolism. Expression of APP decreased
      HMG-CoA reductase (HMGCR)-mediated cholesterol biosynthesis and SREBP mRNA
      levels, while its down regulation had opposite effects. APP and SREBP1 co
      immunoprecipitated and co-localized in the Golgi. This interaction prevented Site
      2 protease-mediated processing of SREBP1, leading to inhibition of transcription
      of its target genes. A GXXXG motif in APP sequence was critical for regulation of
      HMGCR expression. In astrocytes, APP and SREBP1 did not interact nor did APP
      affect cholesterol biosynthesis. Neuronal expression of APP decreased both HMGCR
      and cholesterol 24-hydroxylase mRNA levels and consequently cholesterol turnover,
      leading to inhibition of neuronal activity, which was rescued by geranylgeraniol,
      generated in the mevalonate pathway, in both APP expressing and mevastatin
      treated neurons. We conclude that APP controls cholesterol turnover needed for
      neuronal activity.

PMID- 23554173
TI  - Concise review: hematopoietic stem cell transplantation: targeting the thymus.
AB  - Allogeneic hematopoietic stem cell (HSC) transplantation can cure patients
      suffering from diverse genetic and acquired diseases as well as cancers.
      Nevertheless, under conditions where T-cell reconstitution is critical, the entry
      of donor progenitors into the thymus remains a major bottleneck. It is assumed
      that following the intravenous injection of HSC, they first home to the BM. More
      committed progenitors can then be exported to the thymus in response to a myriad
      of signals regulating thymus seeding. Notably although, the thymus is not
      continually receptive to the import of hematopoietic progenitors. Furthermore, as
      stem cells with self-renewing capacity do not take up residence in the thymus
      under physiological conditions, the periodic colonization of the thymus is
      essential for the sustained differentiation of T lymphocytes. As such, we and
      others have invested significant efforts into exploring avenues that might foster
      a long-term thymus-autonomous differentiation. Here, we review strategic
      approaches that have resulted in long-term T-cell differentiation in
      immunodeficient (SCID) mice, even across histocompatibility barriers. These
      include the forced thymic entry of BM precursors by their direct intrathymic
      injection as well as the transplantation of neonatal thymi. The capacity of the
      thymus to support hematopoietic progenitors with renewal potential will hopefully
      promote the development of new therapeutic strategies aimed at enhancing T-cell
      differentiation in patients undergoing HSC transplantation.

PMID- 23554174
TI  - Mixed-linker hybrid superpolyhedra for the production of a series of large-pore
      iron(III) carboxylate metal-organic frameworks.

PMID- 23554171
TI  - Actin filament dynamics impacts keratinocyte stem cell maintenance.
AB  - Cultured human epidermal keratinocyte stem cells (holoclones) are crucial for
      regenerative medicine for burns and genetic disorders. In serial culture,
      holoclones progressively lose their proliferative capacity to become transient
      amplifying cells with limited growth (paraclones), a phenomenon termed clonal
      conversion. Although it negatively impacts the culture lifespan and the success
      of cell transplantation, little is known on the molecular mechanism underlying
      clonal conversion. Here, we show that holoclones and paraclones differ in their
      actin filament organization, with actin bundles distributed radially in
      holoclones and circumferentially in paraclones. Moreover, actin organization sets
      the stage for a differing response to epidermal growth factor (EGF), since EGF
      signalling induces a rapid expansion of colony size in holoclones and a
      significant reduction in paraclones. Furthermore, inhibition of PI3K or Rac1 in
      holoclones results in the reorganization of actin filaments in a pattern that is
      similar to that of paraclones. Importantly, continuous Rac1 inhibition in
      holoclones results in clonal conversion and reduction of growth potential.
      Together, our data connect loss of stem cells to EGF-induced colony dynamics
      governed by Rac1.

PMID- 23554175
TI  - Toll-like receptor 3 activation modulates hippocampal network excitability, via
      glial production of interferon-beta.
AB  - The family of toll-like receptors (TLR) plays a major role in innate immunity due
      to their pathogen-recognition abilities. TLR3 is a sensor for double-stranded
      RNA, and regulates host-defense responses to several viruses, via the production
      of type I interferons. Interferon-beta (IFNbeta) is a primary product of TLR3
      activation, and its transcription is elevated in the CNS response to the
      synthetic TLR3 ligand, polyinosinic-polycytidylic acid (poly(I:C)). Peripheral
      infections, along with TLR-induced inflammatory mediators, are known to have
      detrimental effects on brain function, exerting a negative impact on cognition
      and enhancing seizure susceptibility. In this study, we assessed hippocampal
      function in vitro, in response to systemic delivery of a TLR3 agonist. Unlike
      agonists of other TLRs, intraperitoneal injection of poly(I:C) did not adversely
      affect evoked short- and long-term synaptic plasticity in mouse hippocampal
      slices. However, sustained and interictal-like spontaneous activity was observed
      in CA1 pyramidal cells in response to poly(I:C) and this was associated with
      alterations in the expression of phosphorylated NR2B subunit-containing NMDA
      receptors and an astrocyte-specific glutamate/aspartate transporter (GLAST) which
      impact on extracellular glutamate concentration and contribute to the genesis of
      epileptiform activity. We provide evidence for the production of IFNbeta from
      microglia and astrocytes, and using mice deficient in the type I IFN receptor
      alpha 1 (IFNAR1), demonstrate that its subsequent activation is likely to
      underlie the TLR3-mediated modulation of hippocampal excitability.

PMID- 23554176
TI  - Time pressure undermines performance more under avoidance than approach
      motivation.
AB  - Four experiments were designed to test the hypothesis that performance is
      particularly undermined by time pressure when people are avoidance motivated. The
      results supported this hypothesis across three different types of tasks,
      including those well suited and those ill suited to the type of information
      processing evoked by avoidance motivation. We did not find evidence that stress
      related emotions were responsible for the observed effect. Avoidance motivation
      is certainly necessary and valuable in the self-regulation of everyday behavior.
      However, our results suggest that given its nature and implications, it seems
      best that avoidance motivation is avoided in situations that involve (time)
      pressure.

PMID- 23554177
TI  - Are narcissists sexy? Zeroing in on the effect of narcissism on short-term mate
      appeal.
AB  - This research was aimed to provide a comprehensive test of the classic notion
      that narcissistic individuals are appealing as short-term romantic or sexual
      partners. In three studies, we tested the hypotheses that narcissism exerts a
      positive effect on an individual's mate appeal and that this effect is mediated
      by high physical attractiveness and high social boldness. We implemented a
      multimethod approach and used ratings of opposite sex persons (Study 1), ratings
      of friends (Study 2), and records of courtship outcomes in naturalistic
      interactions (Study 3) as indicators of mate appeal. In all cases, narcissism had
      a positive effect on mate appeal, which was mainly due to the agentic self
      enhancement aspects of narcissism (rather than narcissists' lacking communion).
      As predicted, physical attractiveness and social boldness mediated the positive
      effect of narcissism on mate appeal. Findings further indicated that narcissism
      was more strongly linked to mate appeal than to friend appeal. 

PMID- 23554178
TI  - Myeloma cell morphology and morphometry in correlation with clinical stages and
      survival.
AB  - Multiple myeloma (MM) shows great variability in clinical course of the disease,
      and survival varies between a few months and more than 10 years. Myeloma plasma
      cells (PCs) can appear completely "normal" in morphology, but can also be overtly
      atypical, polymorphic, immature, as well as in all transitional forms. The aim of
      this investigation was to analyze the relationship between various morphological
      and morphometric parameters of myeloma cells, common staging/prognostic systems
      and survival in patients with MM. Sixty newly diagnosed MM patients were included
      in the study. Morphologic as well as basic morphometric features of myeloma PCs
      were analyzed in bone marrow (BM) aspirates, and compared with patient's clinical
      stage determined by Durie-Salmon and International Staging System, and with
      survival. We conclude that myeloma cell morphology has a prognostic potential.
      The most significant morphologic characteristics indicating shorter survival are:
      finding of >15% atypical PCs in BM aspirate, largest nuclear diameter/largest
      cytoplasmatic diameter of PCs ratio (maxND/maxCD)>=0.65, and anisocytosis
      expressed as standard deviation of maxCD >=4.2 um. Furthermore, PCs with
      irregular nuclei and absence of paranuclear clearing of the cytoplasm indicate
      more advanced stage of disease and worse prognosis. This preliminary results
      obtained on myeloma cells morphology and morphometry should be confirmed in the
      larger study which will include cytogenetic data as well as a therapeutic
      protocols applied.

PMID- 23554179
TI  - Postcranial pneumaticity and bone structure in two clades of neognath birds.
AB  - Most living birds exhibit some degree of postcranial skeletal pneumaticity,
      aeration of the postcranial skeleton by pulmonary air sacs and/or directly from
      the lungs. The extent of pneumaticity varies greatly, ranging from taxa that are
      completely apneumatic to those with air filling most of the postcranial skeleton.
      This study examined the influence of skeletal pneumatization on bone structural
      parameters in a sample of two size- and foraging-style diverse (e.g., subsurface
      diving vs. soaring specialists) clades of neognath birds (charadriiforms and
      pelecaniforms). Cortical bone thickness and trabecular bone volume fraction were
      assessed in one cervical and one thoracic vertebra in each of three pelecaniform
      and four charadriiform species. Results for pelecaniforms indicate that
      specialized subsurface dive foragers (e.g., the apneumatic anhinga) have thicker
      cortical bone and a higher trabecular bone volume fraction than their non-diving
      clademates. Conversely, the large-bodied, extremely pneumatic brown pelican
      (Pelecanus occidentalis) exhibits thinner cortical bone and a lower trabecular
      bone volume fraction. Such patterns in bone structural parameters are here
      interpreted to pertain to decreased buoyancy in birds specialized in subsurface
      dive foraging and decreased skeletal density (at the whole bone level) in birds
      of larger body size. The potential to differentially pneumatize the postcranial
      skeleton and alter bone structure may have played a role in relaxing constraints
      on body size evolution and/or habitat exploitation during the course of avian
      evolution. Notably, similar patterns were not observed within the equally diverse
      charadriiforms, suggesting that the relationship between pneumaticity and bone
      structure is variable among different clades of neognath birds.

PMID- 23554180
TI  - MOF-polymer composite microcapsules derived from Pickering emulsions.
AB  - Hollow composite microcapsules are prepared by the assembly of pre-formed
      nanocrystals of metal-organic frameworks (MOFs) around emulsion droplets,
      followed by interfacial polymerisation of the interior. The micropores of the MOF
      crystals embedded within a semipermeable hierarchically structured polymeric
      membrane are an effective combination for the retention of encapsulated dye
      molecules. Release can be triggered however by acid dissolution of the MOF
      component.

PMID- 23554181
TI  - Lanthanide-based, near-infrared luminescent and magnetic lipoparticles:
      monitoring particle integrity.

PMID- 23554182
TI  - Performances of the Assessment of SpondyloArthritis International Society axial
      spondyloarthritis criteria for diagnostic and classification purposes in patients
      visiting a rheumatologist because of chronic back pain: results from a
      multicenter, cross-sectional study.
AB  - OBJECTIVE: To evaluate the performances (sensitivity, specificity, and positive
      and negative predictive values) at diagnosis and study visit of the Assessment of
      SpondyloArthritis international Society (ASAS) criteria in axial
      spondyloarthritis in patients with chronic back pain (CBP). A secondary objective
      was to identify the most contributory item to diagnosis/classify
      spondyloarthritis. METHODS: We conducted a multicenter, cross-sectional study.
      Patients were ages <45 years with a history of CBP and seeing a rheumatologist in
      France. Data included items from the different sets of criteria, checking if
      present at diagnosis ("diagnosis")/after diagnosis, but at study visit
      ("classification"), and the rheumatologist's diagnosis at study visit.
      Statistical analysis included descriptive characteristics and performances for
      diagnosis and classification. The diagnosis of the rheumatologist was considered
      the "gold standard." RESULTS: A total of 1,210 patients were eligible for our
      analysis. Sensitivity and specificity for ASAS axial criteria were 0.76 and 0.94,
      respectively, and 0.87 and 0.92 for diagnostic and classification purposes,
      respectively. The positive likelihood ratio of the ASAS axial criteria was 13.6
      and 10.30 for diagnostic and classification purposes, respectively. The most
      contributory items to diagnosis and classification were radiographic
      sacroiliitis, followed by magnetic resonance imaging sacroiliitis for diagnosis
      and history of uveitis for classification. CONCLUSION: We confirm the validity of
      the ASAS criteria for both diagnostic and classification purposes in a clinical
      setting of patients with CBP.

PMID- 23554184
TI  - Development of a guided bone regeneration device using salicylic acid
      poly(anhydride-ester) polymers and osteoconductive scaffolds.
AB  - Successful repair of craniofacial and periodontal tissue defects ideally involves
      a combined therapy that includes inflammation modulation, control of soft tissue
      infiltration, and bone regeneration. In this study, an anti-inflammatory polymer,
      salicylic acid-based poly(anhydride-ester) (SAPAE) and a three-dimensional
      osteoconductive ceramic scaffold were evaluated as a combined guided bone
      regeneration (GBR) system for concurrent control of inflammation, soft tissue
      ingrowth, and bone repair in a rabbit cranial defect model. At time periods of 1,
      3, and 8 weeks, five groups were compared: (1) scaffolds with a solid ceramic cap
      (as a GBR structure); (2) scaffolds with no cap; (3) scaffolds with a
      poly(lactide-glycolide) cap; (4) scaffolds with a slow release SAPAE polymer cap;
      and (5) scaffolds with a fast release SAPAE polymer cap. Cellular infiltration
      and bone formation in these scaffolds were evaluated to assess inflammation and
      bone repair capacity of the test groups. The SAPAE polymers suppressed
      inflammation and displayed no deleterious effect on bone formation. Additional
      work is warranted to optimize the anti-inflammatory action of the SAPAE, GBR
      suppression of soft tissue infiltration, and stimulation of bone formation in the
      scaffolds and create a composite device for successful repair of craniofacial and
      periodontal tissue defects.

PMID- 23554185
TI  - When do fat taxes increase consumer welfare? Comment on a claim by Lusk and
      Schroeter.

PMID- 23554186
TI  - Prevalence and characteristics of the epidemic multiresistant Escherichia coli
      ST131 clonal group among extended-spectrum beta-lactamase-producing E. coli
      isolates in Copenhagen, Denmark.
AB  - We report the characteristics of 115 extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli clinical isolates, from 115 unique Danish patients,
      over a 1-year study interval (1 October 2008 to 30 September 2009). Forty-four
      (38%) of the ESBL isolates represented sequence type 131 (ST13)1, from
      phylogenetic group B2. The remaining 71 isolates were from phylogenetic groups D
      (27%), A (22%), B1 (10%), and B2 (3%). Serogroup O25 ST131 isolates (n = 42; 95%
      of ST131) comprised 7 different K antigens, whereas two ST131 isolates were
      O16:K100:H5. Compared to non-ST131 isolates, ST131 isolates were associated
      positively with CTX-M-15 and negatively with CTX-M-1 and CTX-M-14. They also were
      associated positively with 11 virulence genes, including afa and dra (Dr family
      adhesins), the F10 papA allele (P fimbria variant), fimH (type 1 fimbriae), fyuA
      (yersiniabactin receptor), iha (adhesin siderophore), iutA (aerobactin receptor),
      kpsM II (group 2 capsules), malX (pathogenicity island marker), ompT (outer
      membrane protease), sat (secreted autotransporter toxin), and usp
      (uropathogenicity-specific protein) and negatively with hra (heat-resistant
      agglutinin) and iroN (salmochelin receptor). The consensus virulence gene profile
      (>90% prevalence) of the ST131 isolates included fimH, fyuA, malX, and usp (100%
      each), ompT and the F10 papA allele (95% each), and kpsM II and iutA (93% each).
      ST131 isolates were also positively associated with community acquisition,
      extraintestinal pathogenic E. coli (ExPEC) status, and the O25, K100, and H4
      antigens. Thus, among ESBL E. coli isolates in Copenhagen, ST131 was the most
      prevalent clonal group, was community associated, and exhibited distinctive and
      comparatively extensive virulence profiles, plus a greater variety of capsular
      antigens than reported previously.

PMID- 23554187
TI  - Identification of an influenza A H1N1/2009 virus with mutations in the matrix
      gene causing a negative result by a commercial molecular assay.

PMID- 23554188
TI  - Clostridium difficile ribotype diversity at six health care institutions in the
      United States.
AB  - Capillary-based PCR ribotyping was used to quantify the presence/absence and
      relative abundance of 98 Clostridium difficile ribotypes from clinical cases of
      disease at health care institutions in six states of the United States.
      Regionally important ribotypes were identified, and institutions in close
      proximity did not necessarily share more ribotype diversity than institutions
      that were farther apart.

PMID- 23554189
TI  - Fifty percent tissue culture infective dose assay for determining the titer of
      infectious human herpesvirus 8.
AB  - We have developed a human herpesvirus 8 (HHV-8) 50% tissue culture infective dose
      (TCID50) assay using the T1H6-DC-SIGN cell line. Infection of T1H6-DC-SIGN cells
      with HHV-8 induces expression of beta-galactosidase, which was used to determine
      TCID50 levels. Validation of TCID50 values was performed by immunofluorescence
      assay of HHV-8 infection of immature dendritic cells at various TCID50 doses.

PMID- 23554190
TI  - A case of endocarditis caused by Lactococcus garvieae and suggested methods for
      identification.
AB  - Lactococcus garvieae is a Gram-positive coccus that has morphological and
      biochemical similarities to enterococci. L. garvieae strains rare human
      pathogens, with only a few cases reported in the literature, mainly as a cause of
      infective endocarditis. L. garvieae is well known as a fish pathogen, and in some
      of the reported cases, the patients had a history of contact with raw fish. Some
      of the reported endocarditis patients had valvular damage as a predisposing
      condition. We report a case of L. garvieae endocarditis in a patient with no
      history of contact with raw fish and with history of valvular repair in an
      unaffected heart valve.

PMID- 23554191
TI  - Mobile digital fluorescence microscopy for diagnosis of tuberculosis.
AB  - Access to sputum smear microscopy in high-tuberculosis (TB)-burden regions is
      limited by a scarcity of microscopes and experienced technicians. We evaluated
      the accuracy of CellScope, a novel digital fluorescence microscope that may
      expand access to microscopy. The study utilized smear microscopy slides prepared
      from sputum specimens submitted by consecutive adults with >= 2 weeks of cough
      who were admitted to Mulago Hospital (Kampala, Uganda). Conventional light
      emitting diode (LED) fluorescence microscopy (FM) and mycobacterial culture were
      performed by experienced technicians. Two U.S.-based postgraduate researchers
      without prior microscopy experience restained, imaged, and interpreted the slides
      using CellScope. We assessed whether sensitivity and specificity of CellScope
      based LED FM was noninferior to conventional LED FM by using a preselected margin
      of inferiority of 15%. Of 525 patients included, 72% were HIV seropositive and
      39% had culture-confirmed TB. The proportions of positive results were similar
      with CellScope and conventional LED FM (34% versus 32%, respectively; P = 0.32),
      and agreement was substantial. CellScope accuracy was within the noninferiority
      margin for both sensitivity (63% versus 70%; difference, -7%; 95% confidence
      interval [CI], -13% to -1%) and specificity (85% versus 92%; difference, -7%; 95%
      CI, -12% to -3%). A subanalysis of 43 slides evaluated by each CellScope reader
      found substantial interreader reliability (custom-weighted kappa, 0.65) and
      variable intrareader reliability (custom-weighted kappa, 0.11 versus 0.48).
      CellScope offers promise for expanding microscopy services. Future studies should
      evaluate the device when operated by health workers in low-resource settings, the
      feasibility of image transmission and analysis by experienced microscopists, and
      the accuracy of automated image analysis algorithms.

PMID- 23554192
TI  - Detection of non-jejuni and -coli Campylobacter species from stool specimens with
      an immunochromatographic antigen detection assay.
AB  - The STAT! Campy immunochromatographic assay for Campylobacter antigen was
      compared to culture for 500 clinical stool specimens. Antigen was detected in six
      culture-negative, PCR-positive specimens. C. upsaliensis, a pathogenic species
      that is traditionally difficult to recover in routine stool cultures, was
      detected in two of these culture-negative specimens. This study provides evidence
      that antigen testing may cross-react with at least one additional non-jejuni and 
      coli Campylobacter species that may be missed by routine culture for
      campylobacteriosis.

PMID- 23554193
TI  - Septic arthritis and concern for osteomyelitis in a child with rat bite fever.
AB  - Rat bite fever is a rare infection usually caused by Streptobacillus
      moniliformis. A case of septic arthritis and possible osteomyelitis as sequelae
      of rat bite fever in a pediatric patient is described.

PMID- 23554194
TI  - Comparison of typing methods with a new procedure based on sequence
      characterization for Salmonella serovar prediction.
AB  - As the development of molecular serotyping approaches is critical for Salmonella
      spp., which include >2,600 serovars, we performed an initial evaluation of the
      ability to identify Salmonella serovars using (i) different molecular subtyping
      methods and (ii) a newly implemented combined PCR- and sequencing-based approach
      that directly targets O- and H-antigen-encoding genes. Initial testing was
      performed using 46 isolates that represent the top 40 Salmonella serovars
      isolated from human and nonhuman sources, as reported by the U.S. Centers for
      Disease Control and Prevention and the World Health Organization. Multilocus
      sequence typing (MLST) was able to accurately predict the serovars for 42/46
      isolates and showed the best ability to predict serovars among the subtyping
      methods tested. Pulsed-field gel electrophoresis (PFGE), ribotyping, and
      repetitive extragenic palindromic sequence-based PCR (rep-PCR) were able to
      accurately predict the serovars for 35/46, 34/46, and 30/46 isolates,
      respectively. Among the methods, S. enterica subsp. enterica serovars 4,5,12:i:-,
      Typhimurium, and Typhimurium var. 5- were frequently not classified correctly,
      which is consistent with their close phylogenetic relationship. To develop a PCR-
      and sequence-based serotyping approach, we integrated available data sources to
      implement a combination PCR-based O-antigen screening and sequencing of internal
      fliC and fljB fragments. This approach correctly identified the serovars for
      42/46 isolates in the initial set representing the most common Salmonella
      serovars, as well as for 54/63 isolates representing less common Salmonella
      serovars. Our study not only indicates that different molecular approaches show
      the potential to allow for rapid serovar classification of Salmonella isolates,
      but it also provides data that can help with the selection of molecular
      serotyping methods to be used by different laboratories.

PMID- 23554195
TI  - Evaluation of the NucliSENS EasyQ KPC assay for detection of Klebsiella
      pneumoniae carbapenemase-producing Enterobacteriaceae.
AB  - The NucliSENS EasyQ KPC assay (bioMerieux SA, Marcy l'Etoile, France) was
      compared with a routinely used phenotypic method for detection of
      Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC)-type
      carbapenemases, using 806 stool samples and rectal swabs. Compared with the
      phenotypic method, the EasyQ KPC assay had a sensitivity and specificity of 93.3%
      and 99.0%, respectively, in this setting, with diverse KPC producers not limited
      to ST258 Klebsiella pneumoniae.

PMID- 23554196
TI  - Epidemic spread of multidrug-resistant tuberculosis in Johannesburg, South
      Africa.
AB  - Numerous reports have documented isolated transmission events or clonal outbreaks
      of multidrug-resistant Mycobacterium tuberculosis strains, but knowledge of their
      epidemic spread remains limited. In this study, we evaluated drug resistance,
      strain diversity, and clustering rates in patients diagnosed with multidrug
      resistant (MDR) tuberculosis (TB) at the National Health Laboratory Service
      (NHLS) Central TB Laboratory in Johannesburg, South Africa, between March 2004
      and December 2007. Phenotypic drug susceptibility testing was done using the
      indirect proportion method, while each isolate was genotyped using a combination
      of spoligotyping and 12-MIRU typing (12-locus multiple interspersed repetitive
      unit typing). Isolates from 434 MDR-TB patients were evaluated, of which 238
      (54.8%) were resistant to four first-line drugs (isoniazid, rifampin, ethambutol,
      and streptomycin). Spoligotyping identified 56 different strains and 28 clusters
      of variable size (2 to 71 cases per cluster) with a clustering rate of 87.1%. Ten
      clusters included 337 (77.6%) of all cases, with strains of the Beijing genotype
      being most prevalent (16.4%). Combined analysis of spoligotyping and 12-MIRU
      typing increased the discriminatory power (Hunter Gaston discriminatory index
      [HGDI] = 0.962) and reduced the clustering rate to 66.8%. Resolution of Beijing
      genotype strains was further enhanced with the 24-MIRU-VNTR (variable-number
      tandem repeat) typing method by identifying 15 subclusters and 19 unique strains
      from twelve 12-MIRU clusters. High levels of clustering among a variety of
      strains suggest a true epidemic spread of MDR-TB in the study setting,
      emphasizing the urgency of early diagnosis and effective treatment to reduce
      transmission within this community.

PMID- 23554197
TI  - Development of doxycycline MIC and disk diffusion interpretive breakpoints and
      revision of tetracycline breakpoints for Streptococcus pneumoniae.
AB  - A study was performed to derive susceptibility testing interpretive breakpoints
      for doxycycline with Streptococcus pneumoniae and to reassess breakpoints for
      tetracycline using the requirements defined in Clinical and Laboratory Standards
      Institute (CLSI) document M23-A3. Tetracycline and doxycycline MICs and disk
      diffusion zone sizes were determined on 189 isolates selected from the 2009-2010
      CDC Active Bacterial Core surveillance strain collection according to the testing
      methods described in CLSI documents M07-A8 and M02-A10. Tetracycline and
      doxycycline MICs and zones were compared to each other directly, and the
      reproducibility of MICs and zone diameters for both drugs was determined.
      Scattergrams of tetracycline MICs versus corresponding zone diameters and
      doxycycline MICs versus zones were prepared, and analysis indicated that the
      present CLSI tetracycline MIC and disk breakpoints did not fit the susceptibility
      data for doxycycline. Doxycycline was 1 to 3 dilutions more potent than
      tetracycline, especially in strains harboring the tetM resistance determinant.
      tetM was detected in >= 90% of isolates having tetracycline MICs of >= 4 MUg/ml
      and in >= 90% with doxycycline MICs of >= 1. Limited
      pharmacokinetic/pharmacodynamic (PK/PD) data coupled with application of the
      error-rate bounded method of analysis suggested doxycycline-susceptible
      breakpoints of either <= 0.25 MUg/ml or <= 0.5 MUg/ml, with intermediate and
      resistant breakpoints 1 and 2 dilutions higher, respectively. The disk diffusion
      zone diameter correlates were susceptible at >= 28 mm, intermediate at 25 to 27
      mm, and resistant at <= 24 mm. Revised lower tetracycline MIC breakpoints were
      suggested as susceptible at <= 1 MUg/ml, intermediate at 2 MUg/ml, and resistant
      at >= 4 MUg/ml. Suggested tetracycline disk diffusion zones were identical to
      those of doxycycline.

PMID- 23554198
TI  - Identification of Gram-positive cocci by use of matrix-assisted laser desorption
      ionization-time of flight mass spectrometry: comparison of different preparation
      methods and implementation of a practical algorithm for routine diagnostics.
AB  - This study compared three sample preparation methods (direct transfer, the direct
      transfer-formic acid method with on-target formic acid treatment, and ethanol
      formic acid extraction) for the identification of Gram-positive cocci with matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS). A total of 156 Gram-positive cocci representing the clinically most
      important genera, Aerococcus, Enterococcus, Staphylococcus, and Streptococcus, as
      well as more rare genera, such as Gemella and Granulicatella, were analyzed using
      a Bruker MALDI Biotyper. The rate of correct genus-level identifications was
      approximately 99% for all three sample preparation methods. The species
      identification rate was significantly higher for the direct transfer-formic acid
      method and ethanol-formic acid extraction (both 77.6%) than for direct transfer
      (64.1%). Using direct transfer-formic acid compared to direct transfer, the total
      time to result was increased by 22.6%, 16.4%, and 8.5% analyzing 12, 48, and 96
      samples per run, respectively. In a subsequent prospective study, 1,619 clinical
      isolates of Gram-positive cocci were analyzed under routine conditions by MALDI
      TOF MS, using the direct transfer-formic acid preparation, and by conventional
      biochemical methods. For 95.6% of the isolates, a congruence between conventional
      and MALDI-TOF MS identification was observed. Two major limitations were found
      using MALDI-TOF MS: the differentiation of members of the Streptococcus mitis
      group and the identification of Streptococcus dysgalactiae. The Bruker MALDI
      Biotyper system using the direct transfer-formic acid sample preparation method
      was shown to be a highly reliable tool for the identification of Gram-positive
      cocci. We here suggest a practical algorithm for the clinical laboratory
      combining MALDI-TOF MS with phenotypic and molecular methods.

PMID- 23554199
TI  - Analysis of the matrix-assisted laser desorption ionization-time of flight mass
      spectrum of Staphylococcus aureus identifies mutations that allow differentiation
      of the main clonal lineages.
AB  - Nosocomial infections involving epidemic methicillin-resistant Staphylococcus
      aureus (MRSA) strains are a serious problem in many countries. In order to
      analyze outbreaks, the infectious isolates have to be typed; however, most
      molecular methods are expensive or labor-intensive. Here, we evaluated matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS) of cell extracts for the molecular characterization of S. aureus strains. The
      peak patterns of 401 MRSA and methicillin-susceptible S. aureus (MSSA) strains,
      including clinical and laboratory strains, were analyzed. Database searches
      indicated the peptides that were represented by the corresponding peaks in the
      spectra. The identities of the peptides were confirmed by the sequencing of
      mutants, the expression of antisense RNA fragments that resulted in the knockdown
      of the peptide of interest and the concomitant loss of the signal, or tandem
      MALDI-TOF MS (MALDI-TOF/TOF MS). It was shown that the signals derive mainly from
      stress proteins and ribosomal proteins. Peak shifts that differentiate the main
      S. aureus clonal complexes CC5, CC22, CC8, CC45, CC30, and CC1 correlate to point
      mutations in the respective genes. Retrospective typing of an MRSA outbreak
      showed that it is possible to differentiate unrelated MSSA, MRSA, and borderline
      resistant S. aureus (BORSA) strains isolated from health care workers. In
      conclusion, this method allows for the detection of the epidemic lineages of S.
      aureus during species identification by MALDI-TOF MS analysis.

PMID- 23554200
TI  - Impact of routine real-time PCR testing of imported malaria over 4 years of
      implementation in a clinical laboratory.
AB  - In clinical laboratories, diagnosis of imported malaria is commonly performed by
      microscopy. However, the volume of specimens is generally low and maintaining
      proficiency in reading blood smears, particularly at the species level, is
      challenging in this setting. To address this problem, the Provincial Laboratory
      for Public Health (ProvLab) in Alberta, Canada, implemented real-time PCR for
      routine confirmation of all smear-positive samples in the province. Here we
      report our experience over a 4-year period (2008 to 2012) with this new
      diagnostic algorithm. While detection of Plasmodium falciparum by microscopy
      alone was accurate, real-time PCR served as an important adjunct to microscopy
      for the identification of non-falciparum species. In 18% of cases, the result was
      reported as non-falciparum or the species could not be identified by microscopy
      alone, and in all cases, the species was resolved by real-time PCR. In another 4%
      of cases, the species was misidentified by microscopy. To enhance surveillance
      for malaria, we integrated our demographic, clinical, and laboratory data into a
      new system developed by the Canadian Network for Public Health Intelligence,
      called the Malaria System for Online Surveillance (SOS). Using this application,
      we characterized our patient populations and travel history to identify risk
      factors associated with malaria infection abroad.

PMID- 23554201
TI  - Real-time PCR assay for detection and quantification of Leishmania (Viannia)
      organisms in skin and mucosal lesions: exploratory study of parasite load and
      clinical parameters.
AB  - Earlier histopathology studies suggest that parasite loads may differ between
      cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) lesions and between
      acute and chronic CL. Formal demonstration requires highly sensitive detection
      and accurate quantification of Leishmania in human lesional tissue. In this
      study, we developed a quantitative real-time PCR (qPCR) assay targeting
      minicircle kinetoplast DNA (kDNA) to detect and quantify Leishmania (Viannia)
      parasites. We evaluated a total of 156 lesion biopsy specimens from CL or ML
      suspected cases and compared the quantitative performance of our kDNA qPCR assay
      with that of a previously validated qPCR assay based on the glucose-6-phosphate
      dehydrogenase (G6PD) gene. We also examined the relationship between parasite
      load and clinical parameters. The kDNA qPCR sensitivity for Leishmania detection
      was 97.9%, and its specificity was 87.5%. The parasite loads quantified by kDNA
      qPCR and G6PD qPCR assays were highly correlated (r = 0.87; P < 0.0001), but the
      former showed higher sensitivity (P = 0.000). CL lesions had 10-fold-higher
      parasite loads than ML lesions (P = 0.009). Among CL patients, the parasite load
      was inversely correlated with disease duration (P = 0.004), but there was no
      difference in parasite load according to the parasite species, the patient's age,
      and number or area of lesions. Our findings confirm that CL and recent onset of
      disease (<3 months) are associated with a high parasite load. Our kDNA qPCR assay
      proved highly sensitive and accurate for the detection and quantification of
      Leishmania (Viannia) spp. in lesion biopsy specimens. It has potential
      application as a diagnostic and follow-up tool in American tegumentary
      leishmaniasis.

PMID- 23554202
TI  - Identification and characterization of a peptide affinity reagent for detection
      of noroviruses in clinical samples.
AB  - Norovirus (NoV) is the most common agent of nonbacterial epidemic gastroenteritis
      and is estimated to cause 21 million cases of the disease in the United States
      annually. The antigen enzyme-linked immunosorbent assays (ELISAs) currently
      available for NoV diagnosis detect only certain strains and are approved for use
      in the United States only in epidemics where NoV is suspected. There is a clear
      need for simpler, more rapid, and more reliable diagnostic tools for the
      detection of NoV. In this study, phage display technology was used to screen a
      library of phage displaying random 12-mer peptides for those that bind to Norwalk
      virus virus-like particles (NV VLPs). Three phage clones displaying unique
      peptides were identified, and both the peptide-displaying phages and the peptides
      were confirmed to bind specifically to NV VLPs. The peptide displayed on phage
      clone NV-N-R5-1 was determined to bind to the protruding domain of the VP1 capsid
      protein. This phage also bound to NV VLPs seeded into NoV-negative stool with a
      limit of detection of 1.56 ng NV VLP. This value was comparable to monoclonal
      antibody (MAb) 3912, which is currently used in commercially available assays.
      Furthermore, the NV-N-R5-1 phage exhibited high specificity by detecting NV only
      in previously characterized NV-positive stool samples in contrast to no detection
      in NV-negative stool samples. These data demonstrate that the further development
      of NV-N-R5-1 phage as a diagnostic reagent is possible and might offer several
      distinct advantages over antibodies, such as decreases in the time and cost of
      production and ease of isolating phage against other epidemic strains currently
      circulating as well as those that are emerging.

PMID- 23554203
TI  - Analytical evaluation of GeneXpert CT/NG, the first genetic point-of-care assay
      for simultaneous detection of Neisseria gonorrhoeae and Chlamydia trachomatis.
AB  - GeneXpert CT/NG was evaluated with 372 characterized bacterial strains.
      Sensitivity of 10 genome copies/reaction was obtained for both agents. Four
      Neisseria mucosa and two Neisseria subflava isolates were positive for one of two
      gonococcal targets; however, the assay flagged all as negative. The assay was
      analytically highly sensitive and specific.

PMID- 23554204
TI  - Detection of New Delhi metallo-beta-lactamase (encoded by blaNDM-1) in
      Acinetobacter schindleri during routine surveillance.
AB  - A carbapenem-resistant Alcaligenes faecalis strain was isolated from a
      surveillance swab of a service member injured in Afghanistan. The isolate was
      positive for bla(NDM) by real-time PCR. Species identification was reevaluated on
      three identification systems but was inconclusive. Genome sequencing indicated
      that the closest relative was Acinetobacter schindleri and that bla(NDM-1) was
      carried on a plasmid that shared >99% identity with one identified in an
      Acinetobacter lwoffii isolate. The isolate also carried a novel chromosomally
      encoded class D oxacillinase.

PMID- 23554205
TI  - Microbiological diagnosis of severe diarrhea in kidney transplant recipients by
      use of multiplex PCR assays.
AB  - Diarrhea is a frequent complication after kidney transplantation, ascribed to
      adverse effects of the immunosuppressive therapy in case of negative
      microbiological examination of the stools. The aim of this study was to improve
      the microbiological diagnosis by implementing molecular tests. Fifty-four severe
      diarrhea events that occurred in 49 adult kidney transplant recipients from
      September 2010 to November 2011 were investigated. One or several enteric
      pathogens were detected in 13 (23%) stool samples using classical microbiological
      methods versus 39 (72%) for the seven commercially available multiplex PCR assays
      used retrospectively (P = 0.006). Interestingly, molecular diagnosis identified
      15 multiple infections compared to none using classical techniques. The primary
      pathogens detected were enteropathogenic Escherichia coli (EPEC) (n = 15; 38%),
      Campylobacter spp. (n = 15; 38%), and Norovirus (n = 14; 36%). Specificities for
      Campylobacter and Norovirus infection diagnosis were 75 and 100%, respectively,
      by comparison to reference methods. Based on molecular findings, a cyclosporine
      mycophenolate mofetil combination was identified as a risk factor for developing
      Norovirus-induced diarrhea. Norovirus infections were also responsible for higher
      weight loss than all the other causes of diarrhea. In samples from asymptomatic
      immunocompromised and immunocompetent patients, EPEC but not Norovirus and
      Campylobacter infections were detected at a frequency similar to that observed in
      symptomatic kidney transplant recipients. In conclusion, molecular tools
      significantly improved the detection of single and multiple enteric infections by
      comparison to classical techniques and could quickly become the key element in
      the management of severe acute diarrhea in transplant recipients.

PMID- 23554206
TI  - First case of pulmonary disease caused by a Mycobacterium avium complex strain of
      presumed veterinary origin in an adult human patient.
AB  - We report the first case of pulmonary disease caused by a strain of Mycobacterium
      avium complex of presumed veterinary origin in an elderly patient. All serial
      isolates were identified by multilocus sequence analysis based on rpoB, hsp65,
      and 16S rRNA fragments. Disease persisted despite macrolide-based combination
      antibiotic therapy.

PMID- 23554207
TI  - Serum arginase, a biomarker of treatment efficacy in human African
      trypanosomiasis.
AB  - Arginase serum levels were increased in human African trypanosomiasis patients
      and returned to control values after treatment. Arginase hydrolyzes l-arginine to
      l-ornithine, which is essential for parasite growth. Moreover, l-arginine
      depletion impairs immune functions. Arginase may be considered as a biomarker for
      treatment efficacy.

PMID- 23554208
TI  - Retrospective assessment of transcription-mediated amplification-based screening
      for Trichomonas vaginalis in male sexually transmitted infection clinic patients.
AB  - Transcription-mediated amplification (TMA) enhances detection of Neisseria
      gonorrhoeae and Chlamydia trachomatis from rectal and pharyngeal sources. The
      utility of TMA for detection of Trichomonas vaginalis has recently been
      described. We report on the performance of TMA for detection of sexually
      transmitted infection (STI) agents from extraurogenital sources, with a focus on
      T. vaginalis. Within a 21-month interval, 1,314 consecutive male patient
      encounters at an STI clinic resulted in collection of 2,408 specimens for C.
      trachomatis, N. gonorrhoeae, and T. vaginalis TMA screening. A total of 471
      encounters were managed with a single specimen collection (94.9% urine), with
      12.7% positive for at least one STI agent. This detection percentage increased to
      14.4% with collection of specimens from two sources and to 20.3% with collection
      from three sources (P = 0.03 versus single-source sampling). A total of 44.4% of
      encounters were managed by collection of urine and pharyngeal specimens and 19.1%
      by the addition of a third (rectal) collection. While procurement of urine and
      rectal specimens resulted in greater detection of C. trachomatis (6.1% and 11.3%
      rates, respectively) than of other STI agents, 858 pharyngeal specimens yielded a
      2.9% T. vaginalis detection rate compared with 2.1% for N. gonorrhoeae and 1.6%
      for C. trachomatis. All T. vaginalis pharyngeal detections were confirmed by TMA
      based alternative target testing. A total of 38.1% of T. vaginalis-positive
      pharyngeal specimens were derived from symptomatic patient encounters. A total of
      85.7% of males with T. vaginalis-positive pharyngeal collections indicated
      strictly heterosexual preference. Additional specimen source sampling is
      necessary to make STI screening comprehensive. Incorporation of extraurogenital
      sources into assessment for T. vaginalis detection may identify additional
      symptomatic and asymptomatic male STI carriers.

PMID- 23554211
TI  - Low-level laser therapy can produce increased aggressiveness of dysplastic and
      oral cancer cell lines by modulation of Akt/mTOR signaling pathway.
AB  - Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several
      medical applications, including wound healing, reduction of pain and amelioration
      of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic
      cells have been so far poorly studied. Head and neck cancer patients receiving
      LLLT for oral mucositis, for example, might have remaining tumor cells that could
      be stimulated by LLLT. This study demonstrated that LLLT (GaAlAs--660 nm or 780
      nm, 40 mW, 2.05, 3.07 or 6.15 J/cm2) can modify oral dysplastic cells (DOK) and
      oral cancer cells (SCC9 and SCC25) growth by modulating the Akt/mTOR/CyclinD1
      signaling pathway; LLLT significantly modified the expression of proteins related
      to progression and invasion in all the cell lines, and could aggravate oral
      cancer cellular behavior, increasing the expression of pAkt, pS6 and Cyclin D1
      proteins and producing an aggressive Hsp90 isoform. Apoptosis was detected for
      SCC25 and was related to pAkt levels.

PMID- 23554212
TI  - Systematic study of photoluminescence, lyoluminescence and mechanoluminescence in
      Ce3+ - and Eu3+ -activated Li3 PO4 phosphors.
AB  - Li3 PO4 phosphor was prepared using a modified solid-state diffusion technique.
      In this work, photoluminescence, lyoluminescence and mechanoluminescence studies
      were carried out in a Li3 PO4 microcrystalline powder doped with different rare
      earths. In photoluminescence studies, characteristic emission of Ce and Eu was
      observed. The lyoluminescence glow curves of Li3 PO4 microcrystals show that
      lyoluminescence intensity initially increases with time and then decreases
      exponentially. The decay time consists of two components for all masses. The
      dependence of decay time, especially the longer component, on mass has been
      investigated. Experiments on gamma-irradiated crystals have proved that the light
      emission originates from the recombination of released F-centres with trapped
      holes (V2-centres) at the sulfuric acid-solid interface. Incorporation of
      bivalent alkali in solid lithium phosphate leads to an enhancement of
      lyoluminescence. A possible explanation for the experimental results has been
      attempted. The phosphor has a mechanoluminescence single glow peak.
      Mechanoluminescence intensity under various loading conditions was investigated.
      It is observed that mechanoluminescence intensity increases with increasing
      impurity concentration and increasing piston impact velocity. The results may be
      considered as only being of academic interest in solid-state materials.

PMID- 23554213
TI  - Climate change scenarios experiments predict a future reduction in small pelagic
      fish recruitment in the Humboldt Current system.
AB  - The Humboldt Current System (HCS) sustains the world's largest small pelagic
      fishery. While a cooling of this system has been observed during recent decades,
      there is debate about the potential impacts of rising atmospheric CO2
      concentrations on upwelling dynamics and productivity. Recent studies suggest
      that under increased atmospheric CO2 scenarios the oceanic stratification may
      strongly increase and upwelling-favorable winds may remain nearly constant off
      Peru and increase off Chile. Here we investigate the impact of such climatic
      conditions on egg and larval dispersal phases, a key stage of small pelagic fish
      reproduction. We used larval retention rate in a predefined nursery area to
      provide a proxy for the recruitment level. Numerical experiments are based on
      hydrodynamics downscaled to the HCS from global simulations forced by pre
      industrial (PI), 2 * CO2 and 4 * CO2 scenarios. A biogeochemical model is applied
      to the PI and 4 * CO2 scenarios to define a time-variable nursery area where
      larval survival is optimum. We test two distinct values of the oxycline depth
      that limits larval vertical distribution: One corresponding to the present-day
      situation and the other corresponding to a shallower oxycline potentially
      produced by climate change. It appeared that larval retention over the
      continental shelf increases with enhanced stratification due to regional warming.
      However, this increase in retention is largely compensated for by a decrease of
      the nursery area and the shoaling of the oxycline. The underlying dynamics are
      explained by a combination of stratification effects and mesoscale activity
      changes. Our results therefore show that future climate change may significantly
      reduce fish capacity in the HCS with strong ecological, economic and social
      consequences.

PMID- 23554215
TI  - The electronic origin of unusually large (n)J(FN) coupling constants in some
      fluoroximes.
AB  - SOPPA(CCSD) calculations show that the FC term is the most important contribution
      to the through-space transmission of JFN coupling constants for the fluoroximes
      studied in this work. Because of the well-known behavior of FC term, a new
      rationalization for the experimental (TS)JFN SSCC is presented. It is mainly
      based on the overlap matrix (Sij) between fluorine and nitrogen lone pairs
      obtained from NBO analyses. An expression is proposed to take into account the
      influence of the electronic density (Dij) between coupled nuclei as well as the
      s% character at the site of the coupling nuclei of bonds and non-bonding electron
      pairs involved in Dij. In using this approach, a linear correlation between
      (TS)JFN versus Dij is obtained. The most important aspect of this rationalization
      is related to the facility for understanding the behavior of some unusual
      experimental coupling constants. It is shown that, at least in this case, the
      electronic origin of the so-called through-space coupling is transmitted through
      to the overlap of orbitals on the coupled atoms, suggesting that, at least for
      these compounds, instead of through-space coupling, it should better be dubbed as
      'through overlapping orbital coupling'.

PMID- 23554214
TI  - Effect of alginate-chitosan sustained release microcapsules for transhepatic
      arterial embolization in VX2 rabbit liver cancer model.
AB  - Two lipid-solid dispersion loading Norcantharidin sustained-released microspheres
      of alginate-chitosan (NCTD/LSD-ACMs) were prepared via the emulsification
      gelation method. The effects of microspheres for transarterial hepatic
      chemoembolization were evaluated in VX2 rabbit liver cancer model. The VX2 animal
      model was established by biopsy needle, divided randomly into four groups, and
      disposed with three preparations including NCTD/LSD-ACMs (60-120 MUm), NCTD/LSD
      ACMs(120-200 MUm), and NCTD solution through the hepatic arteries compared with
      the untreated group (control group). The serum of all rabbits before and at 3, 7,
      and 14 days after embolization was collected to determine the level of aspartate
      aminotransferase (AST). The AST level increased in the three treated groups on
      the first day compared with the control group (p < 0.05), and was higher in the
      two embolization groups (with no significant difference, p >0.05) than that in
      the NCTD group (p < 0.05). The tumor growth rates, which were significantly
      decreased in the two embolization groups compared with that in the control group,
      and the degree of liver cell necrosis assessed by the histopathological
      specimens, were used to evaluate the embolization effect. Liquefactive necrosis
      and coagulative necrosis were observed in the two embolization groups. The
      results showed that NCTD/LSD-ACMs are a potential candidate for embolization of
      liver cancer.

PMID- 23554216
TI  - Inhibition of microsomal cortisol production by (-)-epigallocatechin-3-gallate
      through a redox shift in the endoplasmic reticulum--a potential new target for
      treating obesity-related diseases.
AB  - Conversion of cortisone to cortisol by 11beta-hydroxysteroid dehydrogenase type 1
      (11betaHSD1) in the endoplasmic reticulum (ER) of the target cells is a major
      determinant of glucocorticoid action, and plays an important role in the
      development of obesity-related diseases. Inhibition of 11betaHSD1 activity is,
      therefore, considered as a promising novel strategy for the treatment of
      metabolic syndrome and diabetes. Tea flavanols and their major representative,
      epigallocatechin gallate are known as antiobesity and antidiabetic agents. Their
      impacts on blood glucose level, hepatic glucose production, and insulin
      responsiveness resemble those observed on inhibition or depletion of 11betaHSD1.
      We aimed to study the effect of epigallocatechin gallate on 11betaHSD1 activity
      in ER-derived rat liver microsomes by measuring cortisone and cortisol with HPLC.
      Cortisol production was efficiently suppressed in a concentration dependent
      manner in intact microsomal vesicles. However, this effect was abolished by
      membrane permeabilization; and the three proteins involved in the overall process
      (11betaHSD1, hexose 6-phosphate dehydrogenase, and glucose 6-phosphate
      transporter) were not or only mildly affected. Further investigation revealed the
      oxidation of luminal NADPH to NADP+, which attenuates cortisone reduction and
      favors cortisol oxidation in this compartment. Such a redox shift in the ER lumen
      might contribute to the beneficial health effects of tea flavanols and should be
      regarded as a promising strategy for the development of novel selective
      11betaHSD1 inhibitors to treat obesity-related diseases.

PMID- 23554217
TI  - Applications of asymptotic confidence intervals with continuity corrections for
      asymmetric comparisons in noninferiority trials.
AB  - A large-sample problem of illustrating noninferiority of an experimental
      treatment over a referent treatment for binary outcomes is considered. The
      methods of illustrating noninferiority involve constructing the lower two-sided
      confidence bound for the difference between binomial proportions corresponding to
      the experimental and referent treatments and comparing it with the negative value
      of the noninferiority margin. The three considered methods, Anbar, Falk-Koch, and
      Reduced Falk-Koch, handle the comparison in an asymmetric way, that is, only the
      referent proportion out of the two, experimental and referent, is directly
      involved in the expression for the variance of the difference between two sample
      proportions. Five continuity corrections (including zero) are considered with
      respect to each approach. The key properties of the corresponding methods are
      evaluated via simulations. First, the uncorrected two-sided confidence intervals
      can, potentially, have smaller coverage probability than the nominal level even
      for moderately large sample sizes, for example, 150 per group. Next, the 15
      testing methods are discussed in terms of their Type I error rate and power. In
      the settings with a relatively small referent proportion (about 0.4 or smaller),
      the Anbar approach with Yates' continuity correction is recommended for balanced
      designs and the Falk-Koch method with Yates' correction is recommended for
      unbalanced designs. For relatively moderate (about 0.6) and large (about 0.8 or
      greater) referent proportion, the uncorrected Reduced Falk-Koch method is
      recommended, although in this case, all methods tend to be over-conservative.
      These results are expected to be used in the design stage of a noninferiority
      study when asymmetric comparisons are envisioned.

PMID- 23554218
TI  - How to assess causality of TMPRSS6 mutations?

PMID- 23554220
TI  - Induction of circularly polarized electroluminescence from an achiral light
      emitting polymer via a chiral small-molecule dopant.
AB  - By simply doping the conventional light-emitting polymer F8BT with a helically
      chiral aromatic molecule, it is shown that substantial levels of CP
      electroluminescence can be generated directly. Both photoluminescent and
      electroluminescent emission from the polymer are observed to become circularly
      polarized, with the sign of the CP emission directly determined by the handedness
      of the dopant.

PMID- 23554221
TI  - The impact of LSIL-H terminology on patient follow-up patterns: a comparison with
      LSIL and ASC-H.
AB  - The Papanicolaou (Pap) test category of "low grade squamous intraepithelial
      lesion, cannot exclude high grade squamous intraepithelial lesion" (LSIL-H) is
      not recognized by The Bethesda System but is commonly used. It is essentially an
      amalgamation of the official LSIL and ASC-H categories. Since these two
      categories have similar follow-up algorithms, the clinical utility of the
      combined LSIL-H category is unclear. We have therefore studied follow-up patterns
      for these three entities in our laboratory to determine the real-world impact of
      each in our patient population. We searched our pathology database over an 18
      month period to find Pap tests (predominantly ThinPrep) interpreted as LSIL-H
      (137), LSIL (2,189), and ASC-H (101). Like other studies, we found that the
      discovery rate of high grade dysplasia in biopsies after LSIL-H (31.9%) was
      similar to ASC-H (35.3%) and was higher than LSIL (7.6%; P < 0.0001). In women
      with no previous history of dysplasia, the frequency of biopsy follow-up after
      the initial Pap test was significantly higher for LSIL-H (68.3%) than for LSIL
      (49.6%; P = 0.0038) and similar to ASC-H (62.3%). We also found that women with
      an initial negative biopsy or a biopsy positive for low grade dysplasia were more
      likely to undergo an additional biopsy if the initial Pap test was LSIL-H (36.2%)
      than if it was LSIL (18.2%; P = 0.0023). ASC-H (26.9%) had an intermediate rate.
      In our patient population, the use of the terminology LSIL-H is associated with
      follow-up biopsy patterns much more similar to ASC-H than to LSIL.

PMID- 23554219
TI  - Regulation of stress granules and P-bodies during RNA virus infection.
AB  - RNA granules are structures within cells that play major roles in gene expression
      and homeostasis. Two principle kinds of RNA granules are conserved from yeast to
      mammals: stress granules (SGs), which contain stalled translation initiation
      complexes, and processing bodies (P-bodies, PBs), which are enriched with factors
      involved in RNA turnover. Since RNA granules are associated with silenced
      transcripts, viruses subvert RNA granule function for replicative advantages.
      This review, focusing on RNA viruses, discusses mechanisms that manipulate stress
      granules and P-bodies to promote synthesis of viral proteins. Three main themes
      have emerged for how viruses manipulate RNA granules; (1) cleavage of key host
      factors, (2) control of protein kinase R (PKR) activation, and (3) redirecting
      RNA granule components for new or parallel roles in viral reproduction, at the
      same time disrupting RNA granules. Viruses utilize one or more of these routes to
      achieve robust and productive infection.

PMID- 23554222
TI  - Accreditation of flow cytometry in Europe.
AB  - ISO 15189 has been introduced to enable any clinical laboratory, irrespective of
      geographic location, to be accredited against internationally recognized
      standards and therefore facilitate direct international comparison of
      laboratories. Together with increasing use of ISO 15189 for standardization and
      competition purposes, often triggered by demands of patients and clinicians,
      clinical flow cytometry laboratories are becoming increasingly challenged to
      introduce compliant quality management systems. Whilst in most countries, ISO
      15189 accreditation is not yet compulsory, there is increasing evidence to
      suggest that the implementation of this standard is growing. As a result, the
      European Society of Clinical Cell Analysis (ESCCA) has analysed the impact of
      accreditation in clinical flow cytometry laboratories. It found, through a
      discussion forum, that staff qualification, adaptation of multicolour antibody
      panels, and implementation of a comprehensive quality system (including quality
      assessment) have been identified as major challenges.

PMID- 23554224
TI  - Synthesis of benzoquinone ansamycin-inspired macrocyclic lactams from shikimic
      acid.

PMID- 23554223
TI  - Repression of Zeb1 and hypoxia cause sequential mesenchymal-to-epithelial
      transition and induction of aid, Oct4, and Dnmt1, leading to immortalization and
      multipotential reprogramming of fibroblasts in spheres.
AB  - In this study, we demonstrate that sphere formation triggers immortalization and
      stable reprogramming of mouse fibroblasts. Cell contact signaling in spheres
      causes downregulation of the epithelial-to-mesenchymal transition transcription
      factor Zeb1 leading to rapid mesenchymal-to-epithelial transition. Hypoxia within
      spheres together with loss of Zeb1 repression synergize to cause superinduction
      of Hif1a, which in turn leads to induction of the DNA demethylase Aid/Aicda,
      demethylation of the Oct4 promoter/enhancer and multipotency. Oct4 and Nanog
      expression diminish when cells are removed from the hypoxic environment of
      spheres and placed in monolayer culture, but the cells retain multipotential
      capacity, demonstrating stable reprogramming and a gene expression pattern
      resembling adult stem cells. Oct4 has been shown to induce Dnmt1 in mesenchymal
      stem cells, and we link Oct4 and Dnmt1 to silencing of cell cycle inhibitory
      cyclin dependent kinase inhibitors and Arf, and immortalization of the
      reprogrammed fibroblasts. Sphere formation then represents a novel and rapid
      protocol for immortalization and stable reprogramming of fibroblasts to
      multipotency that does not require exogenous expression of a stem cell factor or
      a lineage-specifying transcription factor.

PMID- 23554225
TI  - Cell proliferation patterns in early zebrafish development.
AB  - Although cell proliferation is an essential cell behavior for animal development,
      a detailed analysis of spatial and temporal patterns of proliferation in whole
      embryos are still lacking for most model organisms. Zebrafish embryos are
      particularly suitable for this type of analysis due to their transparency and
      size. Therefore, the main objective of the present work was to analyze the
      spatial and temporal patterns of proliferation during the first day of zebrafish
      embryo development by indirect immunofluorescence against phosphorylated histone
      H3, a commonly used mitotic marker. Several interesting findings were
      established. First, we found that mitosis metasynchrony among blastomeres could
      begin at the 2- to 4-cell stage embryos. Second, mitosis synchrony was lost
      before the midblastula transition (MBT). Third, we observed a novel pattern of
      mitotic clusters that coincided in time with the mitotic pseudo "waves" described
      to occur before the MBT. Altogether, our findings indicate that early development
      is less synchronic than anticipated and that synchrony is not a requirement for
      proper development in zebrafish.

PMID- 23554226
TI  - In vivo contribution of nestin- and GLAST-lineage cells to adult hippocampal
      neurogenesis.
AB  - Radial glia-like cells (RGCs) are the hypothesized source of adult hippocampal
      neurogenesis. However, the current model of hippocampal neurogenesis does not
      fully incorporate the in vivo heterogeneity of RGCs. In order to better
      understand the contribution of different RGC subtypes to adult hippocampal
      neurogenesis, we employed widely used transgenic lines (Nestin-CreER(T2) and
      GLAST::CreER(T2) mice) to explore how RGCs contribute to neurogenesis under basal
      conditions and after stimulation and depletion of neural progenitor cells. We
      first used these inducible fate-tracking transgenic lines to define the
      similarities and differences in the contribution of nestin- and GLAST-lineage
      cells to basal long-term hippocampal neurogenesis. We then explored the ability
      of nestin- and GLAST-lineage RGCs to contribute to neurogenesis after
      experimental manipulations that either ablate neurogenesis (i.c.v. application of
      the anti-mitotic AraC, cytosine-beta-D-arabinofuranoside) or stimulate
      neurogenesis (wheel running). Interestingly, in both ablation and stimulation
      experiments, labeled RGCs in GLAST::CreER(T2) mice appear to contribute to
      neurogenesis, whereas RGCs in Nestin-CreER(T2) mice do not. Finally, using
      NestinGFP reporter mice, we expanded on previous research by showing that not all
      RGCs in the adult dentate gyrus subgranular zone express nestin, and therefore
      RGCs are antigenically heterogeneous. These findings are important for the field,
      as they allow appropriately conservative interpretation of existing and future
      data that emerge from these inducible transgenic lines. These findings also raise
      important questions about the differences between transgenic driver lines, the
      heterogeneity of RGCs, and the potential differences in progenitor cell behavior
      between transgenic lines. As these findings highlight the possible differences in
      the contribution of cells to long-term neurogenesis in vivo, they indicate that
      the current models of hippocampal neurogenesis should be modified to include RGC
      lineage heterogeneity.

PMID- 23554227
TI  - Post-traumatic growth among an ethnically diverse sample of adolescent and young
      adult cancer survivors.
AB  - OBJECTIVE: Although some survivors of childhood cancer report significant
      psychosocial distress, many also report having derived benefits, or post
      traumatic growth (PTG), from their cancer experience. This study examines PTG and
      its correlates among an ethnically diverse sample of adolescent/young adult (AYA)
      cancer survivors who have recently completed treatment. METHODS: Survivors of
      childhood cancer (n = 94; 47% Hispanic), ages 11-21 and within 6 months of
      completing cancer therapy, were recruited from three pediatric cancer centers.
      Participants completed a structured interview that assessed demographics, PTG,
      post-traumatic stress symptoms, health-related quality of life, optimism, and
      depressive symptoms. Diagnosis/treatment information was collected from each
      patient's medical record. Multiple regression analyses were used to identify
      significant correlates of PTG. RESULTS: The majority of survivors reported
      positive growth. PTG was positively associated with psychosocial functioning and
      post-traumatic stress symptoms and inversely associated with physical functioning
      and depressive symptoms. PTG was significantly lower among survivors of bone
      tumors (vs. survivors of other cancers) and Hispanic survivors who primarily
      spoke English at home (vs. Hispanics who primarily spoke Spanish at home and non
      Hispanics). PTG was not significantly related to age, sex, optimism, cancer
      treatment modality, duration of treatment, or treatment intensity. CONCLUSIONS:
      The AYA survivors commonly reported PTG in the immediate aftermath of cancer
      treatment. Findings regarding PTG among more acculturated Hispanic and bone tumor
      AYA survivors may help to inform risk-adapted clinical interventions, among those
      transitioning from active treatment to post-treatment surveillance, to mitigate
      negative long-term sequelae and enhance positive psychosocial adaptation from the
      cancer diagnosis and treatment.

PMID- 23554228
TI  - Carboxylation of multiwalled carbon nanotube enhanced its biocompatibility with
      L02 cells through decreased activation of mitochondrial apoptotic pathway.
AB  - Modification of carbon nanotubes (CNTs) with carboxyl group is one of the widely
      used strategies to increase their water dispersibility. Various molecules can be
      further coupled to the surface of carboxylated CNTs for the desired applications.
      However, the effect of carboxylation of CNTs on their cytotoxicity is far from
      being completely understood. In this study, the impact of carboxylated
      multiwalled CNT (MWCNT-COOH) on human normal liver cell line L02 was studied and
      compared with pristine multiwalled CNT (p-MWCNT). The data accumulated in this
      study revealed that modification with carboxyl group reduced the toxicity of
      MWCNT on L02 cells, probably due to the decreased activation of mitochondria
      mediated apoptotic pathway. Both p-MWCNT and MWCNT-COOH, when reaching to certain
      concentration, induced significant decrease in the mitochondrial membrane
      potential, enhanced release of cytochrome c from the mitochondria to cytoplasm as
      well as activation of caspase-9, and -3. However, the changes induced by MWCNT
      COOH were significantly milder than that by p-MWCNT. Our observation suggests
      that carboxylated MWCNTs might be safer for in vivo application as compared with
      p-MWCNT.

PMID- 23554229
TI  - Association of frequent knee bending activity with focal knee lesions detected
      with 3T magnetic resonance imaging: data from the osteoarthritis initiative.
AB  - OBJECTIVE: To evaluate the association of baseline frequent knee bending
      activities with the prevalence and progression of cartilage and meniscal
      abnormalities over 3 years and to assess the effect of frequent knee bending on
      the different knee compartments with 3T magnetic resonance imaging (MRI).
      METHODS: We studied 115 subjects without radiographic knee osteoarthritis (OA)
      but with risk factors for OA from the Osteoarthritis Initiative database. The
      inclusion criteria at baseline were age 45-55 years, body mass index of 19-27
      kg/m(2) , Western Ontario and McMaster Universities Osteoarthritis Index pain
      score of 0, and Kellgren/Lawrence grade <2. Knee bending activities (kneeling,
      squatting, stair climbing, and weight lifting) were assessed by questionnaire at
      the baseline clinic visit. Cartilage and meniscal abnormalities were graded using
      the Whole-Organ MRI Score. Logistic regression was used to determine the
      association of frequent knee bending with cartilage and meniscal abnormalities.
      RESULTS: Frequent knee bending activities were associated with an increased risk
      of prevalent cartilage lesions (odds ratio [OR] 3.63, 95% confidence interval
      [95% CI] 1.39-9.52), in particular in the patellofemoral compartment (OR 3.09,
      95% CI 1.22-7.79). The increase in risk was higher in subjects involved in >=2
      knee bending activities. At 3-year followup, individuals reporting frequent knee
      bending were more likely to show progression of cartilage damage (OR 4.12, 95% CI
      1.27-13.36) and meniscal abnormalities (OR 4.34, 95% CI 1.16-16.32). CONCLUSION:
      Frequent knee bending activities were associated with a higher prevalence of knee
      cartilage lesions (particularly in the patellofemoral compartment) and with an
      increased risk of progression of cartilage and meniscal lesions in asymptomatic
      middle-aged subjects.

PMID- 23554232
TI  - Ordered mesoporous beta-MgMoO4 thin films for lithium-ion battery applications.

PMID- 23554231
TI  - microRNAs are ligands of Toll-like receptors.
AB  - It has long been known that microRNAs (miRNAs) can regulate target gene
      expression at the post-transcriptional level. Recent studies, however, have
      revealed that miRNAs can also be transported from donor cells to recipient cells,
      in which these RNAs function in a novel manner as ligands of Toll-like receptors.
      Here, we review the latest findings on these unconventional miRNAs, with special
      emphasis on their biological significance.

PMID- 23554233
TI  - Synthesis and characterization of a stable, catenated N11 energetic salt.

PMID- 23554234
TI  - Highly selective Lewis acid sites in desilicated MFI zeolites for
      dihydroxyacetone isomerization to lactic acid.
AB  - Desilication of commercial MFI-type (ZSM-5) zeolites in solutions of alkali metal
      hydroxides is demonstrated to generate highly selective heterogeneous catalysts
      for the aqueous-phase isomerization of biobased dihydroxyacetone (DHA) to lactic
      acid (LA). The best hierarchical ZSM-5 sample attains a LA selectivity exceeding
      90 %, which is comparable to that of the state-of-the-art catalyst (i.e., the Sn
      beta zeolite); this optimized hierarchical catalyst is recyclable over three
      runs. The Lewis acid sites, which are created through desilication along with the
      introduction of mesoporosity, are shown to play a crucial role in the formation
      of the desired product; these cannot be achieved by using other post-synthetic
      methods, such as steaming or impregnation of aluminum species. Desilication of
      other metallosilicates, such as Ga-MFI, also leads to high LA selectivity. In the
      presence of a soluble aluminum source, such as aluminum nitrate, alkaline
      assisted alumination can introduce these unique Lewis acid centers in all-silica
      MFI zeolites. These findings highlight the potential of zeolites in the field of
      biomass-to-chemical conversion, and expand the applicability of desilication for
      the generation of selective catalytic centers.

PMID- 23554235
TI  - Migrate or evolve: options for plant pathogens under climate change.
AB  - Findings on climate change influence on plant pathogens are often inconsistent
      and context dependent. Knowledge of pathogens affecting agricultural crops and
      natural plant communities remains fragmented along disciplinary lines. By
      broadening the perspective beyond agriculture, this review integrates cross
      disciplinary knowledge to show that at scales relevant to climate change,
      accelerated evolution and changing geographic distribution will be the main
      implications for pathogens. New races may evolve rapidly under elevated
      temperature and CO2 , as evolutionary forces act on massive pathogen populations
      boosted by a combination of increased fecundity and infection cycles under
      favourable microclimate within enlarged canopy. Changing geographic distribution
      will bring together diverse lineages/genotypes that do not share common
      ecological niche, potentially increasing pathogen diversity. However, the
      uncertainty of model predictions and a lack of synthesis of fragmented knowledge
      remain as major deficiencies in knowledge. The review contends that the failure
      to consider scale and human intervention through new technology are major sources
      of uncertainty. Recognizing that improved biophysical models alone will not
      reduce uncertainty, it proposes a generic framework to increase focus and
      outlines ways to integrate biophysical elements and technology change with human
      intervention scenarios to minimize uncertainty. To synthesize knowledge of
      pathogen biology and life history, the review borrows the concept of 'fitness'
      from population biology as a comprehensive measure of pathogen strengths and
      vulnerabilities, and explores the implications of pathogen mode of nutrition to
      fitness and its interactions with plants suffering chronic abiotic stress under
      climate change. Current and future disease management options can then be judged
      for their ability to impair pathogenic and saprophytic fitness. The review
      pinpoints improving confidence in model prediction by minimizing uncertainty,
      developing management strategies to reduce overall pathogen fitness, and finding
      new sources of data to trawl for climate signatures on pathogens as important
      challenges for future research.

PMID- 23554236
TI  - Insecticidal effect of chlorantraniliprole against major stored-product insect
      pests in different grain commodities under laboratory tests.
AB  - BACKGROUND: Chlorantraniliprole belongs to the chemical group of anthranilic
      diamides. It has selectivity to beneficial arthropods and low mammalian toxicity.
      Laboratory bioassays were conducted to assess chlorantraniliprole as a potential
      grain protectant against Ephestia kuehniella Zeller larvae, Liposcelis
      bostrychophila Badonnel adults, Rhyzopertha dominica (F.) adults, Sitophilus
      oryzae (L.) adults and Tribolium confusum Jacquelin du Val adults and larvae.
      Factors such as dose (0.01, 0.1, 1 and 10 mg chlorantraniliprole kg(-1) grain),
      exposure interval (7 and 14 days), formulation (chlorantraniliprole WG and
      chlorantraniliprole SC) and commodity (barley, maize, oats, peeled rice, whole
      rice and wheat) were evaluated for their impact on the insecticidal activity of
      chlorantraniliprole. Progeny production was assessed after 45 days of exposure in
      the case of L. bostrychophila adults and after 60 days of exposure in the case of
      R. dominica, S. oryzae and T. confusum adults. RESULTS: For L. bostrychophila
      adults, after 7 days of exposure, mortality was lower in maize and whole rice in
      comparison with the other commodities. Increase in dose generally increased
      mortality. Similar trends were also noted after 14 days of exposure. Offspring
      emergence was higher in maize and whole rice in comparison with the other
      commodities. For E. kuehniella larvae, after 7 days of exposure, significant
      differences were noted among the tested commodities. Increase in dose only
      slightly increased mortality in all commodities. After 14 days of exposure,
      mortality was further increased, but did not reach 100%. For R. dominica adults,
      after 7 days of exposure, increase in dose increased mortality significantly.
      After 14 days of exposure, mortality in barley, maize, whole rice and wheat
      exceeded 92% at 10 mg chlorantraniliprole kg(-1) grain. Offspring emergence was
      reduced, but 100% progeny suppression was not achieved. For S. oryzae adults,
      after 7 days of exposure, mortality was generally low at dose rates of <=1 mg
      chlorantraniliprole kg(-1) grain. After 14 days of exposure, 100% mortality was
      noted in whole rice. For T. confusum adults, after 7 days of exposure, mortality
      was low. After 14 days of exposure, mortality increased proportionately for all
      commodities. Most progeny production was noted in oats. For T. confusum larvae,
      after 7 days of exposure, mortality was generally higher in comparison with
      adults. After 14 days of exposure, mortality in maize was high. Generally, the
      two formulations performed alike for all the insects tested. CONCLUSIONS: Based
      on the results of the present work, chlorantraniliprole is effective against
      major stored-product insect species. However, efficacy depends upon the type of
      commodity, the dose rate and the exposure interval.

PMID- 23554237
TI  - Simple and efficient identification of rare recessive pathologically important
      sequence variants from next generation exome sequence data.
AB  - Massively parallel ("next generation") DNA sequencing (NGS) has quickly become
      the method of choice for seeking pathogenic mutations in rare uncharacterized
      monogenic diseases. Typically, before DNA sequencing, protein-coding regions are
      enriched from patient genomic DNA, representing either the entire genome ("exome
      sequencing") or selected mapped candidate loci. Sequence variants, identified as
      differences between the patient's and the human genome reference sequences, are
      then filtered according to various quality parameters. Changes are screened
      against datasets of known polymorphisms, such as dbSNP and the 1000 Genomes
      Project, in the effort to narrow the list of candidate causative variants. An
      increasing number of commercial services now offer to both generate and align NGS
      data to a reference genome. This potentially allows small groups with limited
      computing infrastructure and informatics skills to utilize this technology.
      However, the capability to effectively filter and assess sequence variants is
      still an important bottleneck in the identification of deleterious sequence
      variants in both research and diagnostic settings. We have developed an approach
      to this problem comprising a user-friendly suite of programs that can
      interactively analyze, filter and screen data from enrichment-capture NGS data.
      These programs ("Agile Suite") are particularly suitable for small-scale gene
      discovery or for diagnostic analysis.

PMID- 23554238
TI  - Isolated atrioventricular canal defects: birth outcomes and risk factors: a
      population-based Hungarian case-control study, 1980-1996.
AB  - BACKGROUND: The role of possible environmental factors in the origin of
      congenital heart defects is unclear in the vast majority of patients. The
      objective of this study was to describe the birth outcomes and risk factors in
      isolated atrioventricular canal defect (AVCD) cases. METHODS: Medically recorded
      birth outcomes, maternal age, parity, acute and chronic maternal diseases with
      related drug treatments and folic acid/multivitamin supplementation were
      evaluated in isolated AVCD cases. The diagnosis of AVCD was based on the autopsy
      report or surgical description in the population-based Hungarian Case-Control
      Surveillance of Congenital Abnormalities, between 1980 and 1996. RESULTS: The
      birth outcomes and exposures of 77 isolated AVCD cases were compared with 38,151
      controls without defect. Mean gestational age at delivery (38.6 week) and birth
      weight (2992 g), rate of preterm birth (20.8%) and low birthweight (23.4%) of
      cases with a female excess (59.7%) differed significantly from the controls.
      Mothers of cases had higher parity, higher prevalence of conduction
      disorders/cardiac dysrhythmias and chronic hypertension. The high doses of folic
      acid in early pregnancy associated with a reduced rate of AVCD. CONCLUSIONS:
      Conduction disorders/cardiac dysrhythmias and chronic hypertension of mothers may
      have a role in the origin of AVCD, while high doses of folic acid in early
      pregnancy may reduce the risk of the development of AVCD. Birth Defects Research
      (Part A) 97:217-224, 2013. (c) 2013 Wiley Periodicals, Inc.

PMID- 23554239
TI  - Meta-analysis of healing and prevention of digital ulcers in systemic sclerosis.
AB  - OBJECTIVE: To assess the efficacy of therapies in healing and preventing digital
      ulcers (DUs) in systemic sclerosis (SSc; scleroderma). METHODS: Medline and
      EMBASE databases, and American College of Rheumatology and European League
      Against Rheumatism abstracts, were searched. Randomized controlled trials (RCTs)
      with outcomes investigating healing or prevention of DUs in SSc and comparing a
      pharmacologic therapy with placebo or an active agent were included. The pooled
      risk ratios (RRs) using the fixed-effects model were calculated and heterogeneity
      was tested using the I(2) statistic. RESULTS: Sixty studies were found; 19 were
      not randomized, and 10 did not give DU quantitative data or no comparison of a
      different drug, leaving 31 RCTs with a total of 1,989 patients. Quality was 3 of
      5 or less for 11 trials. DUs were not the primary outcome in many RCTs.
      Phosphodiesterase type 5 (PDE-5) inhibitors were significant for DU healing (RR
      3.28 [95% confidence interval (95% CI) 1.32, 8.13], P = 0.01). Two large bosentan
      trials were significant for mean number of new DUs (standardized mean difference
      [SMD] -0.34 [95% CI -0.57, -0.11], P = 0.004). Oral prostacyclins were not
      statistically different from placebo, but intravenous (IV) iloprost prevented new
      DUs (SMD 0.77 [95% CI -1.46, -0.08], P = 0.03). Single trials for atorvastatin
      and vitamin E were positive in the prevention and healing of DU, respectively.
      There were many negative trials: antiplatelet therapy, oral N-acetylcysteine,
      heparin, dimethyl sulfoxide, ketanserin, prazosin, prostaglandin E1, cyclofenil,
      quinapril, and topical nitroglycerin formulation. CONCLUSION: Small sample sizes,
      few comparative trials, and heterogeneity limits the conclusions. The results
      suggest a role for PDE-5 inhibitors in the healing of DUs; bosentan and IV
      iloprost may prevent new DUs.

PMID- 23554240
TI  - Hexamethoxyphenalenyl as a possible quantum spin simulator: an electronically
      stabilized neutral pi radical with novel quantum coherence owing to extremely
      high nuclear spin degeneracy.

PMID- 23554242
TI  - Virtual reconstruction of very large skull defects featuring partly and
      completely missing midsagittal planes.
AB  - Despite the development of computer-based methods, cranial reconstruction of very
      large skull defects remains a challenge particularly if the damage affects the
      midsagittal region hampering the usage of mirror imaging techniques. This pilot
      study aims to deliver a new method that goes beyond mirror imaging, giving the
      possibility to reconstruct crania characterized by large missing areas, which
      might be useful in the fields of paleoanthropology, bioarcheology, and forensics.
      We test the accuracy of digital reconstructions in cases where two-thirds or more
      of a human cranium were missing. A three-dimensional (3D) virtual model of a
      human cranium was virtually damaged twice to compare two destruction
      reconstruction scenarios. In the first case, a small fraction of the midsagittal
      region was still preserved, allowing the application of mirror imaging
      techniques. In the second case, the damage affected the complete midsagittal
      region, which demands a new approach to estimate the position of the midsagittal
      plane. Reconstructions were carried out using CT scans from a sample of modern
      humans (12 males and 13 females), to which 3D digital modeling techniques and
      geometric morphometric methods were applied. As expected, the second simulation
      showed a larger variability than the first one, which underlines the fact that
      the individual midsagittal plane is of course preferable in order to minimize the
      reconstruction error. However, in both simulations the Procrustes mean shape was
      an effective reference for the reconstruction of the entire cranium, producing
      models that showed a remarkably low error of about 3 mm, given the extent of
      missing data.

PMID- 23554241
TI  - Characterization of bone mineral-resembling biomaterials for optimizing human
      osteoclast differentiation and resorption.
AB  - Bioresorption is a biological mechanism by which biomaterials are resorbed and
      thereby disappear from implantation sites partially or completely over a period
      of time. Osteoclast-medicated bioresorption is a possible new advantage to
      incorporate material degradation into remodeling in bone metabolism process. The
      purpose of this study was to investigate the osteoclastogenesis and bioresorption
      of synthesized calcium phosphate materials. Differentiation into mature human
      osteoclasts on carbonated hydroxyapatite (CA) was significantly enhanced compared
      to hydroxyapatite (HA) and beta-tricalcium phosphate, based on the quantitative
      gene expressions of molecular markers for osteoclast differentiation. Osteoclasts
      adhered and differentiated into giant multinuclear TRAP-positive cells on every
      type of synthesized sample based on the histological analysis. Morphological
      observations using fluorescence and quantitative analysis revealed that the actin
      rings of osteoclasts on CA were thick, small in diameter and co-localized with
      vinculin, similar to the rings found on bone slices. In contrast, the actin rings
      of osteoclasts on HA and culture dishes were thin and large in diameter. Scanning
      electron microscopic images and quantitative analysis indicated that the
      resorption pits on CA were significantly deeper than those on HA due to the
      enhanced tight sealing ability between osteoclasts and their substrate.

PMID- 23554243
TI  - Colloid-in-liquid crystal gels that respond to biomolecular interactions.
AB  - This paper advances the design of stimuli-responsive materials based on colloidal
      particles dispersed in liquid crystals (LCs). Specifically, thin films of colloid
      in-liquid crystal (CLC) gels undergo easily visualized ordering transitions in
      response to reversible and irreversible (enzymatic) biomolecular interactions
      occurring at the aqueous interfaces of the gels. In particular, LC ordering
      transitions can propagate across the entire thickness of the gels. However,
      confinement of the LC to small domains with lateral sizes of ~10 MUm does change
      the nature of the anchoring transitions, as compared to films of pure LC, due to
      the effects of confinement on the elastic energy stored in the LC. The effects of
      confinement are also observed to cause the response of individual domains of the
      LC within the CLC gel to vary significantly from one to another, indicating that
      manipulation of LC domain size and shape can provide the basis of a general and
      facile method to tune the response of these LC-based physical gels to interfacial
      phenomena. Overall, the results presented in this paper establish that CLC gels
      offer a promising approach to the preparation of self-supporting, LC-based
      stimuli-responsive materials. 

PMID- 23554245
TI  - Editorial: stem cell engineering - discovery, diagnostics and therapies.
AB  - Stem cell engineering - discovery, diagnostics and therapies: This Special Issue
      is edited by Brenda Ogle and Sean Palecek and is based on presentations from the
      Third International Conference on Stem Cell Engineering, co-sponsored by the
      Society of Biological Engineering and the International Society for Stem Cell
      Research, held in Seattle, WA from April 29-May 2, 2012.

PMID- 23554248
TI  - Studying cell-cell communication in co-culture.

PMID- 23554252
TI  - Can we improve the positive predictive value of atypical glandular cells not
      otherwise specified?
AB  - The category of atypical glandular cells (AGC) in gynecologic cytopathology
      presents many well-documented diagnostic challenges, the most significant related
      to high interobserver variability, low specificity, and low positive predictive
      value. The current Bethesda System provides criteria for specific glandular
      categories including atypical endocervical cells not otherwise specified (AEC
      NOS), AEC favor neoplastic, and atypical endometrial cells. The Bethesda System
      does, however, acknowledge that in some cases AGC cannot be categorized based
      upon cell of origin, in which case the generic term "atypical glandular cells"
      (AGC) may be used. We sought to determine whether further refinement of the
      current Bethesda System criteria for AEC-NOS might increase the positive
      predictive value of the general category of AGC. Fifty-three cases of AGC with
      documented histologic follow-up at the University of Illinois Hospital were
      reviewed. The cases were graded on each of the eight specific cytologic criteria
      recommended by the current Bethesda System for AEC-NOS using a study-developed
      three-tier grading system. Multiple regression analysis showed that four of the
      cytologic criteria in combination--nuclear enlargement, nuclear pleomorphism,
      increased nuclear-to-cytoplasmic (N/C) ratio, and cells occurring in sheets and
      strips with cell crowding and nuclear overlap--discriminated positive histologic
      outcome slightly better than any single criterion alone. In addition, simple
      logistic regression analysis showed nuclear enlargement to have a marginal
      independent association with positive histologic outcome (P = 0.0566). No other
      criterion was independently associated with outcome. Ancillary methods seem
      indicated to increase the positive predictive value of AGC at this time.

PMID- 23554249
TI  - Perivascular cells in blood vessel regeneration.
AB  - Vascular engineering seeks to design and construct functional blood vessels
      comprising endothelial cells (ECs) and perivascular cells (PCs), with the
      ultimate goal of clinical translation. While EC behavior has been extensively
      investigated, PCs play an equally significant role in the development of novel
      regenerative strategies, providing functionality and stability to vessels. The
      two major classes of PCs are vascular smooth muscle cells (vSMCs) and pericytes;
      vSMCs can be further sub-classified as either contractile or synthetic. The
      inclusion of these cell types is crucial for successful regeneration of blood
      vessels. Furthermore, understanding distinctions between vSMCs and pericytes will
      enable improved therapeutics in a tissue-specific manner. Here we focus on the
      approaches and challenges facing the use of PCs in vascular regeneration,
      including their characteristics, stem cell sources, and interactions with ECs.
      Finally, we discuss biochemical and microRNA (miR) regulators of PC behavior and
      engineering approaches that mimic various cues affecting PC function.

PMID- 23554253
TI  - Comparative cytotoxicity, oxidative stress, and cytokine secretion induced by two
      cyanotoxin variants, microcystin LR and RR, in human intestinal Caco-2 cells.
AB  - While MC-LR and MC-RR share significant structural similarity, MC-RR is less
      cytotoxic than MC-LR. In the current study, we have compared the effects of MC-LR
      and MC-RR in Caco-2 cells by evaluating cytotoxicity, oxidative stress (reactive
      oxygen species production), and the cellular proinflammatory response (IL-6 and
      IL-8 production). Following treatment with 100 uM microcystins (MC), cytotoxicity
      was two-fold greater with MC-LR as compared to MC-RR after 24 h exposure. Whereas
      the reactive oxygen species production and IL-6 secretion were similar following
      a 24-h treatment with either MC, 100 uM MC-LR induced a five-fold greater IL-8
      secretion when compared to MC-RR. Our study has demonstrated that, although both
      MC-LR and MC-RR induced some cytotoxicity in human intestinal cells, a major
      difference in IL-8 production was observed between the two variants.

PMID- 23554255
TI  - Arrayed lentiviral barcoding for quantification analysis of hematopoietic
      dynamics.
AB  - Our understanding of system dynamics of mixed cell populations in whole organisms
      has benefited from the advent of individual cell marking by nonarrayed DNA
      barcodes subsequently analyzed by high-throughput DNA sequencing. However, key
      limitations include statistical biases compromising quantification and the lack
      of applicability to deconvolute individual cell fate in vivo after pooling single
      cells differentially exposed to different conditions ex vivo. Here, we have
      derived an arrayed lentiviral library of DNA barcodes and obtained a proof-of
      concept of its resolving capacity by quantifying hematopoietic regeneration after
      engraftment of mice with genetically modified autologous cells. This method has
      helped clarify and bridge the seemingly opposed clonal-succession and continuous
      recruitment models of hematopoietic stem cell behavior and revealed that myeloid
      lymphoid biases are common occurrences in steady-state hematopoiesis. Arrayed
      lentiviral barcoding should prove a versatile and powerful approach to
      deconvolute cell dynamics in vivo with applications in hematology, embryology,
      and cancer biology.

PMID- 23554256
TI  - Examining the formulation of emulsion electrospinning for improving the release
      of bioactive proteins from electrospun fibers.
AB  - Emulsion electrospinning has been sought as a method to prepare fibrous
      materials/scaffolds for growth factor delivery. Emulsion conditions, specifically
      sonication and the addition of a surfactant, were evaluated to determine their
      effect on the release and bioactivity of proteins from electrospun scaffolds.
      Polycaprolactone (PCL) and poly(ethylene oxide) (PEO/PCL) blends were evaluated
      where PEO, a hydrophilic polymer, was shown to enhance the incorporation of
      proteins. Electrospun scaffolds prepared with the addition of the nonionic
      surfactant Span(r) 80 at a concentration greater than the critical micelle
      concentration followed by mild sonication (10% amplitude) released lysozyme, the
      model protein, with a higher level of bioactivity as compared with other
      surfactant and sonication conditions. These conditions were then used to prepare
      emulsions of platelet-derived growth factor-BB (PDGF-BB) in PEO/PCL blends.
      Electrospun mats prepared by emulsions consisting of PDGF-BB incorporated with
      Span(r) 80 and sonicated at 10% amplitude exhibited a controlled release of PDGF
      BB over 96 h as compared with a more rapid release from solutions that were not
      emulsified (Direct Addition) or emulsions that did not receive Span(r) 80 or
      sonication. Bioactive PDGF-BB incorporated in electrospun scaffolds enhanced the
      osteogenic differentiation of human mesenchymal stem cells as evidenced by
      increased alkaline phosphatase activity, improved cell attachment and reorganized
      cytoskeletal filaments. The findings in this study provide improved methods for
      achieving controlled release of bioactive proteins from electrospun materials.

PMID- 23554257
TI  - TIM3 expression by leukemic and non-leukemic myeloblasts.
AB  - BACKGROUND: T-cell immunoglobulin mucin-3 (TIM3) has recently been described as
      an acute myeloid leukemia (AML) stem cell antigen expressed on leukemic
      myeloblasts, but not on normal hematopoietic stem cells. TIM3 is also expressed
      by monocytes, natural killer cells, and several T cell subsets; however, normal
      myeloblasts have not been well-characterized or compared to AML. A specific flow
      cytometric marker capable of separating leukemic myeloblasts from non-neoplastic
      myeloblasts would be diagnostically useful, especially in the post-chemotherapy
      setting. METHODS: TIM3 myeloblast expression was assessed in 69 bone marrow
      and/or peripheral blood specimens, including 27 AML and 42 non-neoplastic cases
      (20 with a recent history of chemotherapy). TIM3 median fluorescence intensity
      (MFI) was evaluated within myeloblast, monocyte, T cell, and natural killer cell
      populations. RESULTS: The median percentage of myeloblasts positive for TIM3 was
      lower in non-neoplastic specimens without a history of recent chemotherapy
      (50.3%) as compared to AML (71.4%), but not significantly different as compared
      to non-leukemic myeloblasts in the post-chemotherapy setting (72.4%). Mean
      myeloblast TIM3 MFI was higher in AML myeloblasts and non-leukemic myeloblasts in
      the post-chemotherapy setting as compared to non-neoplastic myeloblasts in cases
      lacking a history of chemotherapy. Mean monocyte, natural killer cell, and T-cell
      TIM3 MFI remained relatively constant in varied clinical settings. CONCLUSIONS:
      We confirm that leukemic myeloblasts overexpress TIM3 as compared to non
      neoplastic controls; however, high levels of expression may also be seen among
      non-leukemic myeloblasts in the post-chemotherapy setting. This overlap limits
      the diagnostic utility of TIM3 as a specific marker of neoplasia.

PMID- 23554259
TI  - PFRU, a single dominant locus regulates the balance between sexual and asexual
      plant reproduction in cultivated strawberry.
AB  - Strawberry (Fragaria sp.) stands as an interesting model for studying flowering
      behaviour and its relationship with asexual plant reproduction in polycarpic
      perennial plants. Strawberry produces both inflorescences and stolons (also
      called runners), which are lateral stems growing at the soil surface and
      producing new clone plants. In this study, the flowering and runnering behaviour
      of two cultivated octoploid strawberry (Fragaria * ananassa Duch., 2n = 8* = 56)
      genotypes, a seasonal flowering genotype CF1116 and a perpetual flowering
      genotype Capitola, were studied along the growing season. The genetic bases of
      the perpetual flowering and runnering traits were investigated further using a
      pseudo full-sibling F1 population issued from a cross between these two
      genotypes. The results showed that a single major quantitative trait locus (QTL)
      named FaPFRU controlled both traits in the cultivated octoploid strawberry. This
      locus was not orthologous to the loci affecting perpetual flowering (SFL) and
      runnering (R) in Fragaria vesca, therefore suggesting different genetic control
      of perpetual flowering and runnering in the diploid and octoploid Fragaria spp.
      Furthermore, the FaPFRU QTL displayed opposite effects on flowering (positive
      effect) and on runnering (negative effect), indicating that both traits share
      common physiological control. These results suggest that this locus plays a major
      role in strawberry plant fitness by controlling the balance between sexual and
      asexual plant reproduction.

PMID- 23554258
TI  - Quantitative high resolution mapping of HvMLH3 foci in barley pachytene nuclei
      reveals a strong distal bias and weak interference.
AB  - In barley (Hordeum vulgare L.), chiasmata (the physical sites of genetic
      crossovers) are skewed towards the distal ends of chromosomes, effectively
      consigning a large proportion of genes to recombination coldspots. This has the
      effect of limiting potential genetic variability, and of reducing the efficiency
      of map-based cloning and breeding approaches for this crop. Shifting the sites of
      recombination to more proximal chromosome regions by forward and reverse genetic
      means may be profitable in terms of realizing the genetic potential of the
      species, but is predicated upon a better understanding of the mechanisms
      governing the sites of these events, and upon the ability to recognize real
      changes in recombination patterns. The barley MutL Homologue (HvMLH3), a marker
      for class I interfering crossovers, has been isolated and a specific antibody has
      been raised. Immunolocalization of HvMLH3 along with the synaptonemal complex
      transverse filament protein ZYP1, used in conjunction with fluorescence in situ
      hybridization (FISH) tagging of specific barley chromosomes, has enabled access
      to the physical recombination landscape of the barley cultivars Morex and Bowman.
      Consistent distal localization of HvMLH3 foci throughout the genome, and similar
      patterns of HvMLH3 foci within bivalents 2H and 3H have been observed. A
      difference in total numbers of HvMLH3 foci between these two cultivars has been
      quantified, which is interpreted as representing genotypic variation in class I
      crossover frequency. Discrepancies between the frequencies of HvMLH3 foci and
      crossover frequencies derived from linkage analysis point to the existence of at
      least two crossover pathways in barley. It is also shown that interference of
      HvMLH3 foci is relatively weak compared with other plant species.

PMID- 23554260
TI  - Developmental profiles of the murine palatal methylome.
AB  - BACKGROUND: Environmental factors contribute to the etiology of cleft palate
      (CP). Identification of genes that are methylated during development of the
      secondary palate will contribute to a better understanding of the gene
      environment link contributing to CP. METHODS: Genomic DNA fragments from
      secondary palate tissue from gestational days (GDs) 12 to 14 were subjected to
      Selective Enrichment of Methylated DNA (SEMD) and used to probe NimbleGen 2.1M
      mouse promoter arrays. Input (control) and SEMD samples were labeled with Cy3 and
      Cy5, respectively, and used for array hybridization (three arrays per GD). Data
      were analyzed using the Bioconductor package Ringo. Gene methylation was verified
      by pyrosequencing analysis and expression by quantitative real-time PCR. RESULTS:
      A total of 5577 methylated genes were identified during palate development: (1)
      74% of genes were methylated on all three GDs; (2) CpG islands accounted for only
      30% of methylated regions of interest (MRIs); (3) location of MRIs was more often
      observed in gene bodies (73%) than in promoters; (4) evaluation of MRIs on GDs 12
      14 revealed no significant differentially methylated regions; (5) DAVID analysis
      of MRIs revealed that the cadherin and Wnt signaling pathways, as well as
      pathways involved in proteoglycan synthesis, were significantly enriched for
      methylated genes. CONCLUSIONS: Our prior studies identified differentially
      expressed mRNAs and microRNAs in the developing palate. The current study
      complements these studies by identifying genes whose expression may be altered as
      a result of DNA methylation.

PMID- 23554261
TI  - Electrophilic derivatives antagonise pheromone attraction in Cydia pomonella.
AB  - BACKGROUND: Pheromone antagonists are good disruptants of the pheromone
      communication in insects and, as such, have been used in mating disruption
      experiments. In this study, new non-fluorinated electrophilic keto derivatives
      structurally related to the pheromone of Cydia pomonella (codlemone) have been
      synthesised and tested as putative pheromone antagonists. RESULTS: Codlemone (1)
      was prepared in excellent stereoselectivity in a new, iterative approach
      involving two Horner-Wadsworth-Emmons reactions. Methyl ketone (2), keto ester
      (3) and diketone (4) were obtained from codlemone in straightforward approaches
      in good overall yields and excellent stereochemical purity (>=98% E,E). In
      electrophysiology, only compound 2 displayed inhibition of the antennal response
      to the pheromone after presaturation of the antennal receptors. Compounds 2 to 4
      did not inhibit the pheromone-degrading enzyme responsible for codlemone
      metabolism, but mixtures of ketone 2 and diketone 4 with codlemone elicited
      erratic flights on males in a wind tunnel. In the field, blends of either
      compound (2 or 4) with the pheromone caught significantly fewer males than
      codlemone alone. CONCLUSION: Codlemone and the potential antagonists 2 to 4 have
      been synthesised in good yields and excellent stereoselectivity. These chemicals
      behave as pheromone antagonists of the codling moth both in the laboratory and in
      the field.

PMID- 23554262
TI  - Nitrogen and carbon contents and delta(15) N and delta(13) C signatures in six
      bryophyte species: assessment of long-term deposition changes (1980-2010) in
      Spanish beech forests.
AB  - In this study we used recent (2010) and herbarium material (1980) of six
      bryophyte species to assess long-term atmospheric deposition in natural forested
      areas in northern Spain. For this purpose, tissue nitrogen and carbon content, as
      well as delta(13) C and delta(15) N signatures of samples of Hypnum
      cupressiforme, Polytrichastrum formosum, Leucobryum juniperoideum,
      Rhytidiadelphus loreus, Homalothecium lutescens and Diplophyllum albicans were
      analysed and comparisons made between years and species. In addition, the
      usefulness of each of the six species was evaluated. The range of values observed
      was similar to that in other studies carried out in rural areas. Significantly
      lower values were found in 2010 for N (H. cupressiforme), delta(15) N (R. loreus
      and D. albicans), C (R. loreus) and delta(13) C (all except L. juniperoideum).
      Our natural areas are thus now less influenced by atmospheric pollutants than
      they were, most probably due to changes in some traditional local activities.
      Differences were observed between species for all the four parameters studied, so
      different species must not be analysed together. Finally, R. loreus and H.
      lutescens seem to be good bioindicators, sensitive even with a few samples,
      although further studies are needed to corroborate their usefulness.

PMID- 23554263
TI  - Molecular imaging of cancer cells using a bacteriophage-based 129Xe NMR
      biosensor.

PMID- 23554264
TI  - From hazardous waste to valuable raw material: hydrolysis of CCA-treated wood for
      the production of chemicals.
AB  - Solid wood, metal finnish: Instead of burning waste wood treated with chromated
      copper arsenite (CCA) or disposing of it in landfills, the CCA-treated wood can
      be used as a raw material for the production of chemicals. Catalytic or alkaline
      oxidation together with very mild sulfuric acid extraction produces an easily
      enzymatically hydrolyzable material. Usage as a raw material for the chemical
      industry in this manner demonstrates a sustainable and value-added waste
      management process.

PMID- 23554265
TI  - Iodine-catalyzed regioselective sulfenylation of indoles with sulfonyl
      hydrazides.

PMID- 23554267
TI  - Embossing of micropatterned ceramics and their cellular response.
AB  - The aim of this work is to investigate the use of microtopographies in providing
      physical cues to modulate the cellular response of human mesenchymal stem cells
      on ceramics. Two microgrooved patterns (100 MUm/50 MUm, 10 MUm/10 MUm
      groove/pitch) were transcribed reversely onto alumina green ceramic tapes via an
      embossing technique followed by sintering. Characterization of the micropatterned
      alumina surfaces and their cellular response was carried out. Spread and
      polygonal cell morphologies were observed on the wider groove (50 MUm/100 MUm)
      surface. Cells seeded onto the narrow groove (10 MUm/10 MUm) surface aligned
      themselves alongside the grooves, resulting in more elongated cell morphology.
      More osteoid matrix nodules shown by osteopontin and osteocalcin biomarkers were
      detected on the larger grooved surfaces after cell culture of 21 days, indicating
      a greater level of osteogenicity. This study has shown that micropatterned wider
      groove (50 MUm) topographies are more suitable surfaces for improving
      osseointegration of ceramic implants.

PMID- 23554266
TI  - A 4-year-old Amish boy with weakness, arthritis, rash, verbal delay, and failure
      to thrive.

PMID- 23554268
TI  - Graphene in light: design, synthesis and applications of photo-active graphene
      and graphene-like materials.
AB  - Graphene functionalized with photo-active units has become one of the most
      exciting topics of research in the last few years, which remarkably sustains and
      expands the graphene boom. The rise of photo-active graphene in photonics and
      optoelectronics is evidenced by a spate of recent reports on topics ranging from
      photodetectors, photovoltaics, and optoelectronics to photocatalysis. For these
      applications, the fabrication of photo-active graphene through appropriate
      chemical functionalization strategies is essential as pristine graphene has zero
      bandgap and only weak absorption of photons. Written from the chemists' point of
      view, up-to-date chemical functionalization of graphene with various small
      organic molecules, conjugated polymers, rare-earth components, and inorganic
      semiconductors is reviewed. Particular attention is paid to the development of
      graphene functionalized with light-harvesting moieties, including materials
      synthesis, characterization, energy/charge-transfer processes, and applications
      in photovoltaics. Challenges currently faced by researchers and future
      perspectives in this field are also discussed.

PMID- 23554270
TI  - Leopold G. Koss (1920-2012): a multi-author tribute.

PMID- 23554269
TI  - In-depth analysis of hyaline fibromatosis syndrome frameshift mutations at the
      same site reveal the necessity of personalized therapy.
AB  - Hyaline fibromatosis syndrome is an autosomal recessive disease caused by
      mutations in ANTXR2, a gene involved in extracellular matrix homeostasis. Sixty
      percent of patients carry frameshift mutations at a mutational hotspot in exon
      13. We show in patient cells that these mutations lead to low ANTXR2 mRNA and
      undetectable protein levels. Ectopic expression of the proteins encoded by the
      mutated genes reveals that a two base insertion leads to the synthesis of a
      protein that is rapidly targeted to the ER-associated degradation pathway due to
      the modified structure of the cytosolic tail, which instead of being hydrophilic
      and highly disordered as in wild type ANTXR2, is folded and exposes hydrophobic
      patches. In contrast, one base insertion leads to a truncated protein that
      properly localizes to the plasma membrane and retains partial function. We next
      show that targeting the nonsense mediated mRNA decay pathway in patient cells
      leads to a rescue of ANTXR2 protein in patients carrying one base insertion but
      not in those carrying two base insertions. This study highlights the importance
      of in-depth analysis of the molecular consequences of specific patient mutations,
      which even when they occur at the same site can have drastically different
      consequences.

PMID- 23554271
TI  - Sex differences in spatial abilities of medical graduates entering residency
      programs.
AB  - Sex differences favoring males in spatial abilities have been known by cognitive
      psychologists for more than half a century. Spatial abilities have been related
      to three-dimensional anatomy knowledge and the performance in technical skills.
      The issue of sex differences in spatial abilities has not been addressed formally
      in the medical field. The objective of this study was to test an a priori
      hypothesis of sex differences in spatial abilities in a group of medical
      graduates entering their residency programs over a five-year period. A cohort of
      214 medical graduates entering their specialist residency training programs was
      enrolled in a prospective study. Spatial abilities were measured with a redrawn
      Vandenberg and Kuse Mental Rotations Tests in two (MRTA) and three (MRTC)
      dimensions. Sex differences favoring males were identified in 131 (61.2%) female
      and 83 (38.8%) male medical graduates with the median (Q1, Q3) MRTA score [12 (8,
      14) vs. 15 (12, 18), respectively; P < 0.0001] and MRTC score [7 (5, 9) vs. 9 (7,
      12), respectively; P < 0.0001]. Sex differences in spatial abilities favoring
      males were demonstrated in the field of medical education, in a group of medical
      graduates entering their residency programs in a five-year experiment. Caution
      should be exerted in applying our group finding to individuals because a
      particular female may have higher spatial abilities and a particular male may
      have lower spatial abilities.

PMID- 23554273
TI  - Imaging flow cytometry for morphologic and phenotypic characterization of rare
      circulating endothelial cells.
AB  - Endothelial cells in the peripheral circulation are rare events that require
      technically rigorous approaches for detection by flow cytometry. Visualization of
      these cells has been even more demanding, as this has historically required
      extensive enrichment and processing prior to attempting imaging. As a result,
      few, if any, examples exist on images of peripheral blood circulating endothelial
      cells (CECs) that include verification of the cell lineage both phenotypically
      and genomically. In this study, we have devised a method whereby CECs can be
      directly visualized after lysis of red blood cells and staining, without pre
      enrichment or additional processing. Peripheral blood is stained with CD45,
      CD146, CD3, Hoechst, and DAPI to permit identification of CD146 positive,
      nonleukocyte, nucleated, and live cells that fit the description of CECs. These
      cells are imaged using the Amnis ImageStream(X), an imaging flow cytometer.
      Genomic verification of the endothelial nature of these cells is accomplished by
      using an aliquot of the same stained samples for sorting CECs using similar
      gating strategies. This proof of principle of direct imaging of CECs by imaging
      flow cytometry will permit studies to be conducted heretofore not possible, as
      the ImageStream(X) has the capability of detecting additional fluorochromes other
      than those used to identify the CECs. Such potential investigations include
      antigen colocalization or capping, autophagy and apoptosis, morphologic changes
      in response to therapy, and others. Thus, this method will enable a broad range
      of novel studies to be conducted using CECs as surrogates of the endothelium.

PMID- 23554275
TI  - Potent agonists of a hematopoietic stem cell cytokine receptor, c-Mpl.
AB  - Several growth factors feature prominently in the control of hematopoiesis.
      Thrombopoietin, a class I hematopoietic cytokine, plays critical roles in
      regulating hematopoietic stem cell numbers and also stimulates the production and
      differentiation of megakaryocytes, the bone marrow cells that ultimately produce
      platelets. Thrombopoietin interacts with the c-Mpl cell-surface receptor.
      Recently, several peptide and small-molecule agonists and antagonists of c-Mpl
      have been reported. We conducted a bioinformatics and molecular modeling study
      aimed at understanding the agonist activities of peptides that bind to c-Mpl, and
      developed new potent peptide agonists with low nanomolar activity. These agonists
      also show very high activity in human CD34(+) primary cell cultures, and doubled
      the mean blood platelet counts when injected into mice.

PMID- 23554274
TI  - Uterine vasculature remodeling in human pregnancy involves functional
      macrochimerism by endothelial colony forming cells of fetal origin.
AB  - The potency of adult-derived circulating progenitor endothelial colony forming
      cells (ECFCs) is drastically surpassed by their fetal counterparts. Human
      pregnancy is associated with robust intensification of blood flow and vascular
      expansion in the uterus, crucial for placental perfusion and fetal supply. Here,
      we investigate whether fetal ECFCs transmigrate to maternal bloodstream and home
      to locations of maternal vasculogenesis, primarily the pregnant uterus. In the
      first instance, endothelial-like cells, originating from mouse fetuses expressing
      paternal eGFP, were identified within uterine endothelia. Subsequently, LacZ or
      enhanced green fluorescent protein (eGFP)-labeled human fetal ECFCs, transplanted
      into immunodeficient (NOD/SCID) fetuses on D15.5 pregnancy, showed similar
      integration into the mouse uterus by term. Mature endothelial controls (human
      umbilical vein endothelial cells), similarly introduced, were unequivocally
      absent. In humans, SRY was detected in 6 of 12 myometrial microvessels obtained
      from women delivering male babies. The copy number was calculated at 175 [IQR 149
      471] fetal cells per millimeter square endothelium, constituting 12.5% of
      maternal vessel lumina. Cross-sections of similar human vessels, hybridized for Y
      chromosome, positively identified endothelial-associated fetal cells. It appears
      that through ECFC donation, fetuses assist maternal uterine vascular expansion in
      pregnancy, potentiating placental perfusion and consequently their own fetal
      supply. In addition to fetal growth, this cellular mechanism holds implications
      for materno-fetal immune interactions and long-term maternal vascular health.

PMID- 23554276
TI  - Periconceptional paternal smoking and the risk of congenital heart defects: a
      case-control study.
AB  - BACKGROUND: Maternal smoking during pregnancy has been consistently associated
      with an increased risk of congenital heart defects (CHDs). However, few studies
      have reported the association between paternal smoking during pregnancy and CHDs
      among offspring. This report presents the first case-control study to investigate
      the possible association between periconceptional paternal smoking and CHDs in
      China. METHODS: From February 2010 through October 2011, 284 case fetuses with
      nonsyndromic CHDs and 422 control fetuses with no birth defects were recruited.
      The mothers of cases and controls were interviewed regarding whether the fathers
      of fetuses smoked and avoided the mothers while smoking during the
      periconceptional period. An unconditional logistic regression was used to
      calculate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs)
      while controlling for potential confounders. RESULTS: Light paternal smoking
      increased the risk of isolated conotruncal heart defects (AOR, 2.23; 95% CI,
      1.05, 4.73). Medium paternal smoking seemed to be associated with septal defects
      (AOR, 2.04; 95% CI, 1.05, 3.98) and left ventricular outflow tract obstructions
      (AOR, 2.48; 95% CI, 1.04, 5.95). Heavy paternal smoking was also associated with
      isolated conotruncal heart defects (AOR, 8.16; 95% CI, 1.13, 58.84) and left
      ventricular outflow tract obstructions (AOR, 13.12; 95% CI, 2.55, 67.39).
      Paternal smoking with no avoidance behavior was associated with an increased risk
      of these CHDs subtypes. CONCLUSIONS: Periconceptional paternal smoking increased
      the risk of isolated conotruncal heart defects, septal defects and left
      ventricular outflow tract obstructions. The avoidance behavior of paternal
      smokers may decrease the risk of selected CHDs.

PMID- 23554277
TI  - Neuroprotective effects of erythropoietin in patients with carbon monoxide
      poisoning.
AB  - The purpose of this study was to evaluate the efficacy of erythropoietin (EPO)
      for treating patients with carbon monoxide (CO) poisoning. We conducted a
      randomized, prospective study of 103 patients with CO poisoning in two groups: an
      EPO group (n = 54; patients received EPO) and a placebo group (n = 49; patients
      received normal saline). The study endpoints were the functional outcome at day
      30 (the Barthel index and neurologic sequelae), National Institutes of Health
      Stroke Scale (NIHSS) score, and the levels of S-100beta. At 18 days, the NIHSS
      score improved significantly and S-100beta levels significantly decreased in
      patients in the EPO group. At 30 days, patients in the EPO group had a superior
      Barthel index and fewer patients had delayed neurologic sequelae (DNS). This
      study demonstrated that early administration of EPO to patients with CO poisoning
      improved neurological outcomes and reduced the incidence of DNS.

PMID- 23554278
TI  - Surfing in tortoises? Empirical signs of genetic structuring owing to range
      expansion.
AB  - Much of our current knowledge about the genetic dynamics in range expansions
      originates from models, simulations and microcosm experiments that need to be
      corroborated by field data. Here, we report a neutral genetic pattern that
      matches the predictions of the genetic surfing theory. Genetic surfing occurs
      when repeated founding events and genetic drift act on the wave of advance of an
      expanding population, promoting strong spatial structure. In the range expansion
      of the tortoise Testudo graeca from North Africa to southeastern Spain, we found
      several genetic signatures consistent with surfing: a decrease of genetic
      diversity with distance from the initial founder area, clinal patterns in allele
      frequencies, rare African alleles which have become common at distal sites in the
      Spanish range, and stronger spatial differentiation in the expanded range than in
      the original one. Our results provide support for the theory that genetic drift
      can be an important force in shaping the genetic structure of expanding
      populations.

PMID- 23554279
TI  - Riding the crimson tide: mobile terrestrial consumers track phenological
      variation in spawning of an anadromous fish.
AB  - When resources are spatially and temporally variable, consumers can increase
      their foraging success by moving to track ephemeral feeding opportunities as
      these shift across the landscape; the best examples derive from herbivore-plant
      systems, where grazers migrate to capitalize on the seasonal waves of vegetation
      growth. We evaluated whether analogous processes occur in watersheds supporting
      spawning sockeye salmon (Oncorhynchus nerka), asking whether seasonal activities
      of predators and scavengers shift spatial distributions to capitalize on
      asynchronous spawning among populations of salmon. Both glaucous-winged gulls and
      coastal brown bears showed distinct shifts in their spatial distributions over
      the course of the summer, reflecting the shifting distribution of spawning
      sockeye salmon, which was associated with variation in water temperature among
      spawning sites. By tracking the spatial and temporal variation in the phenology
      of their principal prey, consumers substantially extended their foraging
      opportunity on a superabundant, yet locally ephemeral, resource. Ecosystem-based
      fishery management efforts that seek to balance trade-offs between fisheries and
      ecosystem processes supported by salmon should, therefore, assess the importance
      of life-history variation, particularly in phenological traits, for maintaining
      important ecosystem functions, such as providing marine-derived resources for
      terrestrial predators and scavengers.

PMID- 23554280
TI  - Developmental mode influences diversification in ascidians.
AB  - Ascidian species (Tunicata: Ascidiacea) usually have tailed, hatching tadpole
      larvae. In several lineages, species have evolved larvae that completely lack any
      tail tissues and are unable to disperse actively. Some tailless species hatch,
      but some do not hatch before going through metamorphosis. We show here that
      ascidian species with the highest speciation rates are those with the largest
      range sizes and tailed hatching larval development. We use methods for examining
      diversification in binary characters across a posterior distribution of trees,
      and show that mode of larval development predicts geographical range sizes.
      Conversely, we find that species with the least dispersive larval development
      (tailless, non-hatching) have the lowest speciation rates and smallest
      geographical ranges. Our speciation rate results are contrary to findings from
      sea urchins and snails examined in the fossil record, and further work is
      necessary to reconcile these disparate results.

PMID- 23554281
TI  - Family-based guilds in the ant Pachycondyla inversa.
AB  - High relatedness promotes the evolution of sociality because potentially costly
      cooperative behaviours are directed towards kin. However, societies, such as
      those of social insects, also benefit from genetic diversity, e.g. through
      enhanced disease resistance and division of labour. Effects of genetic diversity
      have been investigated in a few complex eusocial species. Here, we show that
      genetically based division of labour may also be important in 'simple societies',
      with fewer individuals and limited morphological caste differentiation. The
      ponerine ant Pachycondyla inversa has small colonies, headed by several unrelated
      queens. We show that nest-mate workers from different matrilines engage in
      different tasks, have distinct chemical profiles and associate preferentially
      with kin in the nest, while queens and brood stay together. This suggests that
      genetically based division of labour may precede the evolution of complex
      eusociality and facilitate the existence of low relatedness societies functioning
      as associations of distinct families that mutually benefit from group living.

PMID- 23554282
TI  - Silver-catalyzed nitrogenation of alkynes: a direct approach to nitriles through
      C=C bond cleavage.

PMID- 23554283
TI  - Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: To investigate the efficacy and safety of creatine supplementation in
      fibromyalgia patients. METHODS: A 16-week, randomized, double-blind, placebo
      controlled, parallel-group trial was conducted. Fibromyalgia patients were
      randomly assigned to receive either creatine monohydrate or placebo in a double
      blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle
      function, aerobic conditioning, cognitive function, quality of sleep, quality of
      life, kidney function, and adverse events were assessed. Muscle
      phosphorylcreatine content was measured through (31) P magnetic resonance
      spectroscopy. RESULTS: After the intervention, the creatine group presented
      higher muscle phosphorylcreatine content when compared with the placebo group
      (+80.3% versus -2.7%; P = 0.04). Furthermore, the creatine group presented
      greater muscle strength than the placebo group in the leg press and chest press
      exercises (+9.8% and +1.2% for creatine versus -0.5% and -7.2% for placebo,
      respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was
      greater in the creatine group than in the placebo group (+6.4% versus -3.2%; P =
      0.007). However, no general changes were observed in aerobic conditioning, pain,
      cognitive function, quality of sleep, and quality of life. Food intake remained
      unaltered and no side effects were reported. CONCLUSION: Creatine supplementation
      increased intramuscular phosphorylcreatine content and improved lower- and upper
      body muscle function, with minor changes in other fibromyalgia features. These
      findings introduce creatine supplementation as a useful dietary intervention to
      improve muscle function in fibromyalgia patients.

PMID- 23554284
TI  - Effects of simulated drought on the carbon balance of Everglades short
      hydroperiod marsh.
AB  - Hydrology drives the carbon balance of wetlands by controlling the uptake and
      release of CO2 and CH4 . Longer dry periods in between heavier precipitation
      events predicted for the Everglades region, may alter the stability of large
      carbon pools in this wetland's ecosystems. To determine the effects of drought on
      CO2 fluxes and CH4 emissions, we simulated changes in hydroperiod with three
      scenarios that differed in the onset rate of drought (gradual, intermediate, and
      rapid transition into drought) on 18 freshwater wetland monoliths collected from
      an Everglades short-hydroperiod marsh. Simulated drought, regardless of the onset
      rate, resulted in higher net CO2 losses net ecosystem exchange (NEE) over the 22
      week manipulation. Drought caused extensive vegetation dieback, increased
      ecosystem respiration (Reco ), and reduced carbon uptake gross ecosystem exchange
      (GEE). Photosynthetic potential measured by reflective indices (photochemical
      reflectance index, water index, normalized phaeophytinization index, and the
      normalized difference vegetation index) indicated that water stress limited GEE
      and inhibited Reco . As a result of drought-induced dieback, NEE did not offset
      methane production during periods of inundation. The average ratio of net CH4 to
      NEE over the study period was 0.06, surpassing the 100-year greenhouse warming
      compensation point for CH4 (0.04). Drought-induced diebacks of sawgrass (C3 ) led
      to the establishment of the invasive species torpedograss (C4 ) when water was
      resupplied. These changes in the structure and function indicate that freshwater
      marsh ecosystems can become a net source of CO2 and CH4 to the atmosphere, even
      following an extended drought. Future changes in precipitation patterns and
      drought occurrence/duration can change the carbon storage capacity of freshwater
      marshes from sinks to sources of carbon to the atmosphere. Therefore, climate
      change will impact the carbon storage capacity of freshwater marshes by
      influencing water availability and the potential for positive feedbacks on
      radiative forcing. 

PMID- 23554285
TI  - Evaluation of magnesium-yttrium alloy as an extraluminal tracheal stent.
AB  - Tracheomalacia is a relatively rare problem, but can be challenging to treat,
      particularly in pediatric patients. Due to the presence of mechanically deficient
      cartilage, the trachea is unable to resist collapse under physiologic pressures
      of respiration, which can lead to acute death if left untreated. However, if
      treated, the outcome for patients with congenital tracheomalacia is quite good
      because the cartilage tends to spontaneously mature over a period of 12 to 18
      months. The present study investigated the potential for the use of degradable
      magnesium-3% yttrium alloy (W3) to serve as an extraluminal tracheal stent in a
      canine model. The host response to the scaffold included the formation of a thin,
      vascularized capsule consisting of collagenous tissue and primarily mononuclear
      cells. The adjacent cartilage structure was not adversely affected as observed by
      bronchoscopic, gross, histologic, and mechanical analysis. The W3 stents showed
      reproducible spatial and temporal fracture patterns, but otherwise tended to
      corrode quite slowly, with a mix of Ca and P rich corrosion product formed on the
      surface and observed focal regions of pitting. The study showed that the approach
      to use degradable magnesium alloys as an extraluminal tracheal stent is
      promising, although further development of the alloys is required to improve the
      resistance to stress corrosion cracking and improve the ductility.

PMID- 23554286
TI  - Mechanical properties of decellularized tendon cultured by cyclic straining
      bioreactor.
AB  - Decellularized tissues have been successfully used in tissue engineering and
      regenerative medicine for the purpose of removing antigens present in the
      cellular components. However, this decellularization technique uses ionic
      solutions or chemical treatments such as enzyme treatments that might damage the
      biophysical properties or reduce the physical strength of tissue. This study
      aimed to improve the strength of decellularized tissues. We designed a tissue
      bioreactor that can repeatedly deliver physical stimulation, such as tensile and
      torsional deformation, to the upper and lower parts of a tissue. To
      decellularized porcine Tibialis tendons, we used an enzymatic solution to remove
      the primary cells, and then applied ultrasonic cleansing using a combination of
      ionic solution and distilled water to destroy residual cells by differing from
      the osmotic pressure between the inside and outside of the cell membrane. The
      total DNA content of decellularized tissue was decreased by 77% compared with
      that of the original tissue and the ultimate tensile strength of the
      decellularized tissue was 20% lower than that of the normal tissue.
      Decellularized tissues were then cultivated in the tissue bioreactor with
      repeated physical stimulation of 110% tension, 90 degrees  torsion, and frequency
      of once per a second, and the ultimate tensile strength was found to be greater
      than that of the normal ligament at 7 day culture. This study showed that
      decellularization using enzyme and mechanical treatment is safe and use of a
      tissue bioreactor can increase the physical strength of tendons, making this a
      potential mechanism to reconstruct human ligaments.

PMID- 23554288
TI  - Tenure track: the royal road to professorship?

PMID- 23554287
TI  - pH-Induced lignin surface modification to reduce nonspecific cellulase binding
      and enhance enzymatic saccharification of lignocelluloses.
AB  - We studied the mechanism of the significant enhancement in the enzymatic
      saccharification of lignocelluloses at an elevated pH of 5.5-6.0. Four lignin
      residues with different sulfonic acid contents were isolated from enzymatic
      hydrolysis of lodgepole pine pretreated by either dilute acid (DA) or sulfite
      pretreatment to overcome recalcitrance of lignocelluloses (SPORL). The adsorption
      isotherms of a commercial Trichoderma reesi cellulase cocktail (CTec2) produced
      by these lignin residues at 50  degrees C were measured in the pH range of 4.5
      6.0. The zeta potentials of these lignin samples were also measured. We
      discovered that an elevated pH significantly increased the lignin surface charge
      (negative), which causes lignin to become more hydrophilic and reduces its
      coordination affinity to cellulase and, consequently, the nonspecific binding of
      cellulase. The decreased nonspecific cellulase binding to lignin is also
      attributed to enhanced electrostatic interactions at elevated pH through the
      increased negative charges of cellulase enzymes with low pI. The results validate
      the hypothesis that the increases in enzymatic saccharification efficiencies at
      elevated pH for different pretreated lignocelluloses are solely the result of
      decreased nonspecific cellulase binding to lignin. This study contradicts the
      well-established concept that the optimal pH is 4.8-5.0 for enzymatic hydrolysis
      using Trichoderma reesi cellulose, which is widely accepted and exclusively
      practiced in numerous laboratories throughout the world. Because an elevated pH
      can be easily implemented commercially without capital cost and with minimal
      operating cost, this study has both scientific importance and practical
      significance.

PMID- 23554289
TI  - Cytological diagnosis of metastatic glioblastoma in the pleural effusion of a
      lung transplant patient.
AB  - The extracranial metastasis of glioblastoma is a rare event. We report the case
      of a patient who developed metastatic glioblastoma in pleural effusion 15 months
      after lung transplant, with emphasis on differential diagnosis based on
      cytological material. In our case, tumor cells had pleomorphic nuclei, prominent
      nucleoli, and fine vesicular chromatin. Some were arranged in a poorly formed
      pseudo-glandular architecture, mimicking a poorly differentiated adenocarcinoma.
      The cytological diagnosis of metastatic glioblastoma is difficult and depends
      critically on clinical history and suspicion, particularly in the transplant
      setting. Review of the literature indicates that transmission/metastasis of
      intracranial malignancy occurs rarely following organ transplantation, with some
      debate on the suitability for transplant of organs from affected donors. Although
      the situation is uncommon, this report of the cytological findings of
      extracranial glioblastoma may extend our current knowledge and provide additional
      differential diagnostic information for this entity.

PMID- 23554290
TI  - Diagnostic application and clinical significance of FCM progress scoring system
      based on immunophenotyping in CD34+ blasts in myelodysplastic syndromes.
AB  - BACKGROUND: Abnormal proliferation and differentiation of hematopoietic
      stem/progenitor cells, which reflect the malignant nature of clonal cells in
      myelodysplastic syndromes (MDS), can be detected by flow cytometry (FCM) and
      potentially applied to assist diagnosis and evaluate prognosis in MDS. METHODS:
      In this study, a series of immunophenotypes such as CD34, CD19, CD38, CD117, and
      CD7, which are related to proliferation and differentiation of HSCs, were
      determined by FCM in the patients with nonclonal cytopenias diseases and MDS.
      Based on the expression pattern of these immunophenotypes, a FCM progress scoring
      (FPS) system was constructed and evaluated. RESULTS: The FPS system showed good
      sensitivity and specificity (63.6% and 100.0%) in distinguishing MDS from
      nonclonal cytopenias diseases. Validation analysis of FPS system indicated
      comparable sensitivity and specificity (73.7% and 97.1%) and high agreement rate
      (82.6%) of FCM diagnosis with morphological diagnosis. The high-grade MDS had
      higher FPS score compared to low-grade MDS (P < 0.001). Noticeably, hypocellular
      MDS had lower FPS score (P < 0.001), most of which could not be diagnosed by FPS
      system. Besides, FPS score showed obvious positive correlation with WHO
      classification, IPSS score, percentage of marrow blasts, and cytogenetic
      prognosis scoring. Elevated FPS score predicted higher disease progression and
      shorter survival in MDS. CONCLUSION: The FPS system based on immunophenotyping in
      CD34+ blasts is a useful and simple tool for diagnosis and prognosis evaluation
      in MDS.

PMID- 23554292
TI  - Amorphous Ni(OH)2 nanoboxes: fast fabrication and enhanced sensing for glucose.
AB  - Inspired by Pearson's hard and soft acid-base (HSAB) principle, uniform amorphous
      Ni(OH)2 nanoboxes with intact shell structures and various sizes are quickly
      fabricated by deliberately selecting S2O3(2-) as the coordinating etchant toward
      Cu2O templates and optimizing the reaction conditions. It is found that not only
      the solvent system but also the employing of a surfactant is vital for the
      fabrication of the nanoboxes. Ni(OH)2 nanoboxes, as an example, demonstrate an
      improved electrochemical sensing ability for glucose, which might be due to their
      amorphous and hollow structural features.

PMID- 23554293
TI  - Total synthesis of diaporthichalasin by using the intramolecular Diels-Alder
      reaction of an alpha,beta-unsaturated gamma-hydroxylactam in aqueous media.
AB  - The first total synthesis of diaporthichalasin has been successfully achieved and
      complete structure elucidation, including the absolute configuration, was also
      accomplished. The intramolecular Diels-Alder (IMDA) reaction between the diene
      side chain on the decalin skeleton and alpha,beta-unsaturated gamma-hydroxy-gamma
      lactam in aqueous media was effectively employed as the key step. From this
      synthetic study, we found that alpha,beta-unsaturated gamma-hydroxy-gamma-lactam
      is an essential precursor for the construction of the diaporthichalasin-type
      pentacyclic skeleton. This important finding strongly suggests that this route is
      involved in the biosynthetic pathway for diaporthichalasin.

PMID- 23554291
TI  - Commonality in Down and fetal alcohol syndromes.
AB  - BACKGROUND: Down syndrome (DS) and Fetal Alcohol Syndrome (FAS) are two leading
      causes of birth defects with phenotypes ranging from craniofacial abnormalities
      to cognitive impairment. Despite different origins, we report that in addition to
      sharing many phenotypes, DS and FAS may have common underlying mechanisms of
      development. METHODS: Literature was surveyed for DS and FAS as well as mouse
      models. Gene expression and apoptosis were compared in embryonic mouse models of
      DS and FAS by qPCR, immunohistochemical and immunoflurorescence analyses. The
      craniometry was examined using MicroCT at postnatal day 21. RESULTS: A literature
      survey revealed over 20 comparable craniofacial and structural deficits in both
      humans with DS and FAS and corresponding mouse models. Similar phenotypes were
      experimentally found in pre- and postnatal craniofacial and neurological tissues
      of DS and FAS mice. Dysregulation of two genes, Dyrk1a and Rcan1, key to
      craniofacial and neurological precursors of DS, was shared in craniofacial
      precursors of DS and FAS embryos. Increased cleaved caspase 3 expression was also
      discovered in comparable regions of the craniofacial and brain precursors of DS
      and FAS embryos. Further mechanistic studies suggested overexpression of trisomic
      Ttc3 in DS embyros may influence nuclear pAkt localization and cell survival.
      CONCLUSIONS: This first and initial study indicates that DS and FAS share common
      dysmorphologies in humans and animal models. This work also suggests common
      mechanisms at cellular and molecular levels that are disrupted by trisomy or
      alcohol consumption during pregnancy and lead to craniofacial and neurological
      phenotypes associated with DS or FAS.

PMID- 23554294
TI  - Alterations in the cellular immune compartment of patients treated with third
      party mesenchymal stromal cells following allogeneic hematopoietic stem cell
      transplantation.
AB  - Adoptive transfer of third-party mesenchymal stromal cells (MSCs) has emerged as
      a promising tool for the treatment of steroid-refractory graft-versus-host
      disease (GVHD). Despite numerous in vitro studies and preclinical models, little
      is known about their effects on the patients' immune system. We assessed immune
      alterations in the T-cell, B-cell, natural killer cell, dendritic cell, and
      monocytic compartments of steroid-refractory GVHD patients 30, 90, and 180 days
      after MSC (n = 6) or placebo (n = 5) infusion, respectively. Infused MSCs were
      bioactive as suggested by the significant reduction in epithelial cell death,
      which represents a biomarker for acute GVHD. There were several indications that
      MSCs shift the patients' immune system toward a more tolerogenic profile. Most
      importantly, infusion of MSCs was associated with increased levels of regulatory
      (forkhead box P3 (FOXP3)(+) and interleukin (IL)-10(+) ) T-cells, reduced pro
      inflammatory IL-17(+) T(Th17)-cells, and skewing toward type-2 T-helper cell
      responses. Furthermore, IL-2, which has been recently shown to exert a positive
      immune modulating effect in GVHD patients, was higher in the MSC patients at all
      evaluated time points during 6 months after MSC-infusion. Overall, our findings
      will contribute to the refinement of monitoring tools, for assessing MSC
      treatment-efficacy and increase our understanding regarding the MSCs' in vivo
      effects.

PMID- 23554296
TI  - Alternating block polyurethanes based on PCL and PEG as potential nerve
      regeneration materials.
AB  - Polyurethanes with regular and controlled block arrangement, i.e., alternating
      block polyurethanes (abbreviated as PUCL-alt-PEG) based on poly(epsilon
      caprolactone) (PCL-diol) and poly(ethylene glycol) (PEG) was prepared via
      selectively coupling reaction between PCL-diol and diisocyanate end-capped PEG.
      Chemical structure, molecular weight, distribution, and thermal properties were
      systematically characterized by FTIR, (1)H NMR, GPC, DSC, and TGA. Hydrophilicity
      was studied by static contact angle of H2O and CH2I2. Film surface was observed
      by scanning electron microscope (SEM) and atomic force microscopy, and mechanical
      properties were assessed by universal test machine. Results show that alternating
      block polyurethanes give higher crystal degree, higher mechanical properties, and
      more hydrophilic and rougher (deep ravine) surface than their random counterpart,
      due to regular and controlled structure. Platelet adhesion illustrated that PUCL
      alt-PEG has better hemocompatibility and the hemacompatibility was affected
      significantly by PEG content. Excellent hemocompatibility was obtained with high
      PEG content. CCK-8 assay and SEM observation revealed much better cell
      compatibility of fibroblast L929 and rat glial cells on the alternating block
      polyurethanes than that on random counterpart. Alternating block polyurethane
      PUC20-a-E4 with optimized composition, mechanical, surface properties,
      hemacompatibility, and highest cell growth and proliferation was achieved for
      potential use in nerve regeneration.

PMID- 23554297
TI  - Safety and immunogenicity of yellow fever 17D vaccine in adults receiving
      systemic corticosteroid therapy: an observational cohort study.
AB  - OBJECTIVE: To assess the safety and immunogenicity of live attenuated yellow
      fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy.
      METHODS: All adult travelers on systemic corticosteroid therapy who had received
      the YF17D vaccine in 24 French vaccination centers were prospectively enrolled
      and matched with healthy controls (1:2) on age and history of YF17D immunization.
      Safety was assessed in a self-administered standardized questionnaire within 10
      days after immunization. YF-specific neutralizing antibody titers were measured 6
      months after vaccination in patients receiving corticosteroids. RESULTS: Between
      July 2008 and February 2011, 102 vaccine recipients completed the safety study
      (34 receiving corticosteroids and 68 controls). The median age was 54.9 years
      (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of
      previous YF17D immunization. The median time receiving corticosteroid therapy was
      10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day
      (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid
      arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious
      adverse event was reported; however, patients receiving corticosteroids reported
      more frequent moderate/severe local reactions than controls (12% and 2%,
      respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects
      receiving corticosteroids who were tested (n = 20) had neutralizing antibody
      titers >10 after vaccination. CONCLUSION: After YF17D immunization,
      moderate/severe local reactions may be more frequent in patients receiving
      systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale
      studies are needed to confirm these results.

PMID- 23554298
TI  - Maillard degradation pathways of vitamin C.

PMID- 23554300
TI  - Nitric oxide releasing material adsorbs more fibrinogen.
AB  - One mechanism of the failure of blood-contacting devices is clotting. Nitric
      oxide (NO) releasing materials are seen as a viable solution to the mediation of
      surface clotting by preventing platelet activation; however, NO's involvement in
      preventing clot formation extends beyond controlling platelet function. In this
      study, we evaluate NO's effect on factor XII (fibrinogen) adsorption and
      activation, which causes the initiation of the intrinsic arm of the coagulation
      cascade. This is done by utilizing a model plasticized poly(vinyl) chloride
      (PVC), N-diazeniumdiolate system and looking at the adsorption of fibrinogen, an
      important clotting protein, to these surfaces. The materials have been prepared
      in such a way to eliminate changes in surface properties between the control
      (plasticized PVC) and composite (NO-releasing) materials. This allows us to
      isolate NO release and determine the effect on the adsorption of fibrinogen, to
      the material surface. Surprisingly, it was found that an NO releasing material
      with a surface flux of 17.4 +/- 0.5 * 10(-10) mol NO cm(-2) min(-1) showed a
      significant increase in the amount of fibrinogen adsorbed to the material surface
      compared to one with a flux of 13.0 +/- 1.6 * 10(-10) mol NO cm(-2) min(-1) and
      the control (2334 +/- 496, 226 +/- 99, and 103 +/-31% fibrinogen adsorbed of
      control, respectively). This study suggests that NO's role in controlling
      clotting is extended beyond platelet activation.

PMID- 23554299
TI  - Branched-chain amino acid supplementation: impact on signaling and relevance to
      critical illness.
AB  - The changes that occur in mammalian systems following trauma and sepsis, termed
      systemic inflammatory response syndrome, elicit major changes in carbohydrate,
      protein, and energy metabolism. When these events persist for too long they
      result in a severe depletion of lean body mass, multiple organ dysfunction, and
      eventually death. Nutritional supplementation has been investigated to offset the
      severe loss of protein, and recent evidence suggests that diets enriched in
      branched-chain amino acids (BCAAs) may be especially beneficial. BCAAs are
      metabolized in two major steps that are differentially expressed in muscle and
      liver. In muscle, BCAAs are reversibly transaminated to the corresponding alpha
      keto acids. For the complete degradation of BCAAs, the alpha-keto acids must
      travel to the liver to undergo oxidation. The liver, in contrast to muscle, does
      not significantly express the branched-chain aminotransferase. Thus, BCAA
      degradation is under the joint control of both liver and muscle. Recent evidence
      suggests that in liver, BCAAs may perform signaling functions, more specifically
      via activation of mTOR (mammalian target of rapamycin) signaling pathway,
      influencing a wide variety of metabolic and synthetic functions, including
      protein translation, insulin signaling, and oxidative stress following severe
      injury and infection. However, understanding of the system-wide effects of BCAAs
      that integrate both metabolic and signaling aspects is currently lacking. Further
      investigation in this respect will help rationalize the design and optimization
      of nutritional supplements containing BCAAs for critically ill patients.

PMID- 23554301
TI  - What exactly are the cytoplasmic inclusions in metastatic urothelial carcinoma,
      and are they of diagnostic value?

PMID- 23554302
TI  - Foamy virus-adenovirus hybrid vectors for gene therapy of the arthritides.
AB  - BACKGROUND: Genetic treatments of chronic arthritic conditions are essentially
      dependent on safe and efficient vector systems. To combine features of the
      efficient transduction of adenovirus vectors with the advantage of stable
      integration into the host cell genome of apathogenic prototype foamy virus
      vectors, hybrid vectors (FAD) have been established. In the present study, we
      have generated and investigated the use of safe FAD vectors for direct gene
      delivery to joints. METHODS: We generated recombinant FAD encoding enhanced green
      fluorescent protein (EGFP) or human interleukin 1 receptor antagonist protein
      (IL1RA) cDNA, and explored their transgene expression profile, as well as the
      bioactivity of the IL1RA transgene in vitro. The feasibility of IL1RA gene
      delivery to articular tissues was investigated in a pilot study employing direct
      FAD injections to the knee joints of Wistar rats. RESULTS: FAD vectors
      efficiently transduced human or rat fibroblasts with EGFP or IL1RA transgene in
      vitro. Levels of IL1RA transgene expression were high, stable and functional in
      vitro. Transduced synovial fibroblasts and high levels of IL1RA protein (10-35
      ng/ml) could be detected in vivo in the synovium of Wistar rats 3-5 days after
      injection of FAD vectors to the knee joints. CONCLUSIONS: Our results indicate
      that FAD vectors are capable of efficient in vivo gene transfer to synovium and
      merit further investigation as a means of providing efficient and long-term intra
      articular transgene expression for treatment of the arthritides.

PMID- 23554303
TI  - Hydroxyapatite/collagen nanocomposite-coated titanium rod for achieving rapid
      osseointegration onto bone surface.
AB  - This article proposes less-invasive subperiosteal bone-bonding devices capable of
      realizing rapid osseointegration and the acquisition of fundamental knowledge
      required for their development. Three candidates were prepared: titanium rod
      specimens with a machined surface (Bare), hydroxyapatite (HAp) coating, and
      hydroxyapatite/collagen (HAp/Col) nanocomposite coating. To investigate bone
      formation around these rods, each specimen was placed under the periosteum of a
      male Sprague-Dawley rat calvarium. Four weeks after surgery, the samples were
      evaluated via histomorphometrical analyses and bonding strength tests. All the
      Bare specimens and more than half of the HAp specimens were encapsulated with
      fibrous tissue, whereas all the HAp/Col specimens were almost completely
      surrounded by new bone tissue without encapsulation. Histomorphometrical analyses
      showed that the HAp/Col group had the greatest bone contact ratio among all
      candidates (p < 0.05). Further, a bonding strength test indicated that the
      HAp/Col group exhibited the greatest bonding strength to bone (p < 0.05). Thus,
      HAp/Col-coated rods are considered as the best candidate materials for achieving
      rapid osseointegration onto a bone surface.

PMID- 23554305
TI  - Formation of Ag2S cages from polyhedral Ag2O nanocrystals and their
      electrochemical properties.
AB  - Ag2O nanocubes, rhombicuboctahedra, octahedra, and hexapods have been employed as
      templates for the generation of Ag2O-Ag2S core-shell structures through a rapid
      sulfidation process in a basic solution. Addition of an ammonia etching solution
      quickly removes the Ag2O cores, thereby resulting in the formation of Ag2S cages
      with morphologies that resemble the starting templates. The composition of the
      Ag2S shells and cages has been extensively determined by various analytical
      techniques including X-ray and electron diffraction and X-ray photoelectron
      spectroscopy. The Ag2S shells have a monoclinic crystal structure and are
      polycrystalline with some amorphous and porous regions. The nanocage formation
      process has been captured by transmission electron microscopy (TEM). Gap spaces
      are formed initially between the cores and the shells owing to uniform etching of
      the Ag2O cores on all of the faces. No linkages connecting the cores to the
      shells have been observed. Depending on the potential scanning ranges applied,
      four types of electrochemical redox behavior have been identified for the Ag2O
      and Ag2O-Ag2S cubes in a basic solution. The ability to easily fabricate thin
      sheets of Ag2S over different Ag2O surfaces should extend the applications of
      Ag2S nanostructures.

PMID- 23554304
TI  - Gastroschisis is a defect of the umbilical ring: evidence from morphological
      evaluation of stillborn fetuses.
AB  - BACKGROUND: Gastroschisis (GS) is usually described as an abdominal wall defect,
      to the right of a normally inserted umbilical cord, without membraneous covering
      of the extruded organs. However, precise anatomical descriptions are lacking in
      the literature. Our aims were to provide evidence that allows reconsideration of
      its current definition, as well as an explanation for prenatal death, based on
      detailed observation of stillborn fetuses with GS and a review of the literature.
      METHODS: Prenatal studies, clinical examinations, and histological findings of
      five stillborn fetuses with isolated GS are described and photographic evidence
      is provided. RESULTS: In all five cases, the umbilical cord was only attached to
      the left side of the umbilical ring, while the right side remained uncovered,
      allowing evisceration of abdominal organs. Histological evidence of mucoid-like
      tissue at the free border of the ring suggests that at that site the cord was
      initially inserted and later detached. Characteristics of the umbilical ring,
      bowel dilatation, and autopsy findings of acute asphyxia strongly support
      compression of umbilical vessels as the cause of fetal death. CONCLUSIONS: Based
      on these findings, on the lack of evidence in the literature demonstrating full
      thickness abdominal wall separating the defect from the umbilical cord, and on a
      critical review of the proposed mechanisms favoring the hypothesis of a defect
      separate from the umbilical ring, we propose that GS represents a failure in the
      normal attachment between umbilical cord and umbilical ring. The consistent
      clinical course of fetuses with prenatal demise suggests careful targeted
      monitoring during late gestation.

PMID- 23554306
TI  - Long-term outcomes of complete versus incomplete revascularization after drug
      eluting stent implantation in patients with multivessel coronary disease.
AB  - BACKGROUND: A limited number of studies on the impact of complete
      revascularization (CR) vs. incomplete revascularization (IR) on long-term
      outcomes in patients with multivessel coronary disease (MVD) in current
      percutaneous coronary intervention (PCI) practice have yielded inconsistent
      results. METHODS: Between April 2004 and November 2010, 7,376 consecutive
      patients with MVD underwent PCI at the Fuwai Hospital in Beijing, China. Patients
      who underwent prior CABG and those who had an acute myocardial infarction (MI)
      within 24 hr before revascularization or presented with cardiogenic shock were
      excluded. Angiographic CR was defined as successful angioplasty of all diseased
      lesions in the major epicardial coronary vessels and their first degree side
      branches (diameter >=2.5 mm), and proximal CR was defined as successful
      angioplasty of all diseased proximal arteries. RESULTS: Among 7,065 patients with
      MVD undergoing PCI treatment, angiographic CR was performed in 1,188 patients
      (16.8%), and proximal CR in 2,053 patients (29.1%). The study found that either
      angiographic or proximal IR were associated with significantly higher estimated 3
      year rate of cardiac death (2.55% vs. 1.13%, log-rank P = 0.016; and 2.70% vs.
      1.43%, log-rank P = 0.024, respectively). After adjustment for differences in
      baseline characteristics between IR and CR patients, angiographic IR was
      associated with a significantly higher rate of cardiac death (adjusted hazards
      ratio [HR]: 2.56, 95% confidence interval [CI]: 1.03-6.41) while proximal IR was
      associated with a numerically higher rate of cardiac death (adjusted HR: 1.72,
      95% CI: 0.93-3.17). For the subgroup of >=2-vessel IR with total occlusion,
      either angiographic or proximal IR patients had significantly higher rate of
      cardiac death (adjusted HR: 4.25, 95% CI: 1.50-12.09; and adjusted HR: 3.02, 95%
      CI: 1.40-6.52, respectively). CONCLUSION: Compared with IR, patients with CR had
      better clinical outcomes, supporting CR as first choice for patients with MVD.

PMID- 23554307
TI  - Interdigitated multicolored bioink micropatterns by multiplexed polymer pen
      lithography.
AB  - Multiplexing, i.e., the application and integration of more than one ink in an
      interdigitated microscale pattern, is still a challenge for microcontact printing
      (MUCP) and similar techniques. On the other hand there is a strong demand for
      interdigitated patterns of more than one protein on subcellular to cellular
      length scales in the lower micrometer range in biological experiments. Here, a
      new integrative approach is presented for the fabrication of bioactive
      microarrays and complex multi-ink patterns by polymer pen lithography (PPL). By
      taking advantage of the strength of microcontact printing (MUCP) combined with
      the spatial control and capability of precise repetition of PPL in an innovative
      way, a new inking and writing strategy is introduced for PPL that enables true
      multiplexing within each repetitive subpattern. Furthermore, a specific
      ink/substrate platform is demonstrated that can be used to immobilize functional
      proteins and other bioactive compounds over a biotin-streptavidin approach. This
      patterning strategy aims specifically at application by cell biologists and
      biochemists addressing a wide range of relevant pattern sizes, easy pattern
      generation and adjustment, the use of only biofriendly, nontoxic chemicals, and
      mild processing conditions during the patterning steps. The retained bioactivity
      of the fabricated cm(2) area filling multiprotein patterns is demonstrated by
      showing the interaction of fibroblasts and neurons with multiplexed structures of
      fibronectin and laminin or laminin and ephrin, respectively. 

PMID- 23554308
TI  - A pH-sensitive binary drug delivery system based on poly(caprolactone)-heparin
      conjugates.
AB  - PCL-heparin conjugates were synthesized by coupling mono-hydroxyl terminated PCL
      (Mn = 2000-10000 g/mol) with heparin via EDC/NHS chemistry. The conjugates
      enabled to self-assemble into the core-shell nanoparticles in around 100 nm
      diameter to load binary anti-cancer drugs. Lipophilic and neutral paclitaxel
      (PTX) was first encapsulated in the core, and then hydrophilic and positive
      charged doxorubicin (DOX) was incorporated into the negative charged shell of PTX
      loaded nanoparticles via the electrostatic interaction. The in vitro release
      profiles of the binary-drug loaded nanoparticles revealed that both PTX and DOX
      were sustainably released from the particles but behaved differently. The release
      of DOX was pH dependent, ensuring more drug to be released in the tumor cells
      than in the normal ones. Hence these particles were featured by a sequential
      controlled drug delivery behavior with a significant cytotoxicity to cervical
      cancer (Hela cell) and breast cancer (MDA-MB-321) cells. The CLSM observations
      clearly indicated that both loaded PTX and DOX aggregated in the nucleus of tumor
      cells to exert their anti-tumor pharmacodynamic effect on the cells.

PMID- 23554309
TI  - B cell activation is regulated by the stiffness properties of the substrate
      presenting the antigens.
AB  - B lymphocytes are activated upon Ag sensing by BCRs. The substrate presenting the
      Ag can show different degrees of stiffness. It is not clear whether B cells can
      respond to changes in substrate stiffness. In this study we use high-resolution,
      high-speed live cell imaging techniques to capture the molecular events in B cell
      activation after the recognition of Ags tethered to polyacrylamide gel substrates
      with variable degrees of stiffness as quantified by Young's modulus (2.6-22.1
      kPa). We show that the initiation of B cell activation is extremely sensitive to
      substrate stiffness. B cells exhibit much stronger activation responses when
      encountering Ags tethered to substrates with a high degree of stiffness as
      measured by the accumulation of BCR, phospho-spleen tyrosine kinase, and
      phosphotyrosine molecules into the B cell immunological synapse. Ags tethered to
      stiff substrates induce the formation of more prominent BCR and phospho-spleen
      tyrosine kinase microclusters with significantly enhanced colocalization as
      compared with Ags tethered to soft substrates. Moreover, the expression of the B
      cell activation marker CD69 is enhanced in B cells encountering Ags on stiffer
      substrates. Through time-lapse live cell imaging, we find that the different
      responses of B cells to substrate stiffness are only demonstrated 5 min after BCR
      and Ag recognition. Using a series of cytoskeleton inhibitors, we determine that
      the mechanosensing ability of B cells is dependent on microtubules, and only
      mildly linked to the actin cytoskeleton. These results suggest the importance of
      the mechanical properties mediated by substrate stiffness in B cell activation.

PMID- 23554310
TI  - Targeted inhibition of serotonin type 7 (5-HT7) receptor function modulates
      immune responses and reduces the severity of intestinal inflammation.
AB  - Mucosal inflammation in conditions ranging from infective acute enteritis or
      colitis to inflammatory bowel disease is accompanied by alteration in serotonin
      (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an
      important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7
      (5-HT7) receptor is one of the most recently identified members of the 5-HT
      receptor family, and dendritic cells express this receptor. In this study, we
      investigated the effect of blocking 5-HT7 receptor signaling in experimental
      colitis with a view to develop an improved therapeutic strategy in intestinal
      inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or
      dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor
      antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7(-/-)) and
      irradiated wild-type mice reconstituted with bone marrow cells harvested from 5
      HT7(-/-) mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated
      both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted
      in lower clinical disease, histological damage, and proinflammatory cytokine
      levels compared with vehicle-treated mice post-DSS. Colitis severity was
      significantly lower in 5-HT7(-/-) mice and in mice reconstituted with bone marrow
      cells from 5-HT7(-/-) mice compared with control mice after DSS colitis. 5-HT7(-/
      ) mice also had significantly reduced DNBS-induced colitis. These observations
      provide us with novel information on the critical role of the 5-HT7 receptor in
      immune response and inflammation in the gut, and highlight the potential benefit
      of targeting this receptor to alleviate the severity of intestinal inflammatory
      disorders such as inflammatory bowel disease.

PMID- 23554311
TI  - Connexin43 is dispensable for phagocytosis.
AB  - Macrophages that lack connexin43 (Cx43), a gap junction protein, have been
      reported to exhibit dramatic deficiencies in phagocytosis. In this study, we
      revisit these findings using well-characterized macrophage populations. Cx43
      knockout (Cx43(-/-)) mice die soon after birth, making the harvest of macrophages
      from adult Cx43(-/-) mice problematic. To overcome this obstacle, we used several
      strategies: mice heterozygous for the deletion of Cx43 were crossed to produce
      Cx43(+/+) (wild type [WT]) and Cx43(-/-) fetuses. Cells isolated from 12- to 14-d
      fetal livers were used to reconstitute irradiated recipient animals. After
      reconstitution, thioglycollate-elicited macrophages were collected by peritoneal
      lavage and bone marrow was harvested. Bone marrow cells and, alternatively, fetal
      liver cells were cultured in media containing M-CSF for 7-10 d, resulting in
      populations of cells that were >95% macrophages based on flow cytometry.
      Phagocytic uptake was detected using flow cytometric and microscopic techniques.
      Quantification of phagocytic uptake of IgG-opsonized sheep erythrocytes, zymosan
      particles, and Listeria monocytogenes failed to show any significant difference
      between WT and Cx43(-/-) macrophages. Furthermore, the use of particles labeled
      with pH-sensitive dyes showed equivalent acidification of phagosomes in both WT
      and Cx43(-/-) macrophages. Our findings suggest that modulation of Cx43 levels in
      cultured macrophages does not have a significant impact on phagocytosis.

PMID- 23554312
TI  - Efficient attenuation of NK cell-mediated liver injury through genetically
      manipulating multiple immunogenes by using a liver-directed vector.
AB  - Adenovirus or adenoviral vectors were reported to induce serious liver
      inflammation in an NK cell-dependent manner, which limits its clinical
      applicability for liver gene therapy. We tried to develop an efficient liver
      directed therapeutic approach to control hepatic NK cell function via
      simultaneously manipulating multiple immune genes. Based on our previous study,
      we found that CCL5 knockdown synergistically enhanced the attenuating effect of
      silencing CX3CL1 (fractalkine [FKN]) in adenovirus-induced acute liver injury. In
      addition, the combined treatment of human IL-10 expression with FKN knockdown
      would further strengthen the protective effect of silencing FKN. We used a
      hepatocyte-specific promoter to construct a hepatocyte-specific multiple function
      vector, which could simultaneously overexpress human IL-10 and knock down CCL5
      and FKN expression. This vector could attenuate adenovirus-induced acute
      hepatitis highly efficiently by reducing liver NK cell recruitment and serum IFN
      gamma and TNF-alpha. The multiple function vectors could be delivered by nonviral
      (hydrodynamic injection) and viral (adenovirus) approaches, and maintained long
      term function (more than 1 month in mice). Our results suggest a possible
      strategy to ameliorate the acute liver injury induced by adenovirus by modulating
      multiple immune genes. The novel multifunction vector has an extensive and
      practical use for polygenic and complex liver diseases such as malignancies and
      hepatitis, which correlate with multiple gene disorders.

PMID- 23554314
TI  - How changes in fibril-level organization correlate with the macrolevel behavior
      of articular cartilage.
AB  - The primary structural components of articular cartilage are the zonally
      differentiated interconnected network of collagen fibrils and proteoglycans, the
      latter having the potential to bind large amounts of water. Both components exist
      in a coupled relationship that gives rise to its remarkable mechanical
      properties. The response of cartilage to compression is governed both by the
      degree to which the hydrated proteoglycans are constrained within this fibrillar
      network and the ease with which the matrix fluid can be displaced. The functional
      properties of cartilage are therefore closely linked to the integrity of the
      fibrillar network. Our current understanding of this network has been derived via
      studies conducted at the macro, micro, and ultrastructural levels. Of particular
      interest to joint researchers and clinicians are issues relating to how the
      network structure varies both directionally and with zonal depth, how its
      integrity is maintained via mechanisms of fibril interconnectivity, and how it is
      modified by ageing, degeneration, and trauma. Physical models have been developed
      to explore modes of interconnectivity. Combined micromechanical and structural
      studies confirm the critical role that this interconnectivity must play but
      detailed descriptions at the molecular level remain elusive. Current
      computationally based models of cartilage have in some cases implemented the
      fibrillar component, albeit simplistically, as a separate structure. Considering
      how important a role fibril network interconnectivity plays in actual tissue
      structure and mechanical behavior, and especially how it changes with
      degeneration, a major challenge facing joint tissue modellers is how to
      incorporate such a feature in their models.

PMID- 23554315
TI  - Fabrication of a 3D hair follicle-like hydrogel by soft lithography.
AB  - Hair follicle transplantation is often used in the treatment of androgenetic
      alopecia (AGA). However, the only source of hair follicles is from human donors
      themselves, which limits the application of this approach. One possible solution
      is to reconstitute hair follicle from dissociated cells. Currently, a number of
      microscale technologies have been developed to create size and shape controlled
      microenvironments in tissue engineering. Photopolymerizable PEGDA hydrogels are
      often selected as promising scaffolds in engineered microtissues due to their
      biocompatibility and adjustable mechanical properties. Here, we fabricated an
      array of PEGDA microwells with center islets that mimic the architecture of human
      hair follicles using soft lithography. Dermal and epithelial cells were seeded in
      different compartments of the microstructured mould to mimic mesenchymal and
      epithelial compartmentalization in native hair follicles. We demonstrated that
      these compartmentalized microstructures support cell proliferation and cell
      survival over 14 days, and spreading of dermal fibroblasts was observed. This
      hydrogel micromould provides a potentially useful tool for engineering 3D hair
      follicle-mimicking complex cultures in vitro.

PMID- 23554316
TI  - "Leo Koss as I remember him".

PMID- 23554313
TI  - NK cell tolerance of self-specific activating receptor KIR2DS1 in individuals
      with cognate HLA-C2 ligand.
AB  - NK cells are regulated by inhibiting and activating cell surface receptors. Most
      inhibitory receptors recognize MHC class I Ags and protect healthy cells from NK
      cell-mediated autoaggression. However, certain activating receptors, including
      the human activating killer cell Ig-like receptor (KIR) 2DS1, also recognize MHC
      class I. This fact raises the question of how NK cells expressing such activating
      receptors are tolerized to host tissues. We investigated whether the presence of
      HLA-C2, the cognate ligand for 2DS1, induces tolerance in 2DS1-expressing NK
      cells. Anti-HLA-C2 activity could be detected in vitro in some 2DS1 positive NK
      clones irrespective of the presence or absence of HLA-C2 ligand in the donor. The
      frequency of anti-HLA-C2 reactivity was high in donors homozygous for HLA-C1.
      Surprisingly, no significant difference was seen in the frequency of anti-HLA-C2
      cytotoxicity in donors heterozygous for HLA-C2 and donors without HLA-C2 ligand.
      However, donors homozygous for HLA-C2, compared with all other donors, had
      significantly reduced frequency of anti-HLA-C2 reactive clones. The 2DS1 positive
      clones that express inhibitory KIR for self-HLA class I were commonly
      noncytotoxic, and anti-HLA-C2 cytotoxicity was nearly exclusively restricted to
      2DS1 single positive clones lacking inhibitory KIR. 2DS1 single positive NK
      clones with anti-HLA-C2 reactivity were also present posttransplantation in HLA
      C2 positive recipients of hematopoietic stem cell transplants from 2DS1 positive
      donors. These results demonstrate that many NK cells with anti-HLA-C2 reactivity
      are present in HLA-C1 homozygous and heterozygous donors with 2DS1. In contrast,
      2DS1 positive clones from HLA-C2 homozygous donors are frequently tolerant to HLA
      C2.

PMID- 23554318
TI  - Development of a DNA microarray for species identification of quarantine aphids.
AB  - BACKGROUND: Aphid pests are being brought into Korea as a result of increased
      crop trading. Aphids exist on growth areas of plants, and thus plant growth is
      seriously affected by aphid pests. However, aphids are very small and have
      several sexual morphs and life stages, so it is difficult to identify species on
      the basis of morphological features. This problem was approached using DNA
      microarray technology. RESULTS: DNA targets of the cytochrome c oxidase subunit I
      gene were generated with a fluorescent dye-labelled primer and were hybridised
      onto a DNA microarray consisting of specific probes. After analysing the signal
      intensity of the specific probes, the unique patterns from the DNA microarray,
      consisting of 47 species-specific probes, were obtained to identify 23 aphid
      species. To confirm the accuracy of the developed DNA microarray, ten individual
      blind samples were used in blind trials, and the identifications were completely
      consistent with the sequencing data of all individual blind samples. CONCLUSION:
      A microarray has been developed to distinguish aphid species. DNA microarray
      technology provides a rapid, easy, cost-effective and accurate method for
      identifying aphid species for pest control management.

PMID- 23554319
TI  - Molecular assembly of an achiral phosphine and a chiral primary amine: a highly
      efficient supramolecular catalyst for the enantioselective Michael reaction of
      aldehydes with maleimides.
AB  - A combined catalyst system of a cinchonidine-derived primary amine and
      triphenylphosphine (CD-NH2 /PPh3 ) exhibited high catalytic performance in the
      Michael reaction of aldehydes with maleimides, thereby affording the
      corresponding functionalized aldehydes in excellent yields (up to 99 %) and
      enantioselectivities (>99 % ee). More interestingly, the significance of the
      phosphine in enhancing the enantioselectivities in the chiral-primary-amine
      catalyzed Michael reaction was revealed. Furthermore, we explored the origin of
      the reaction mechanism in the Michael addition promoted by the dual
      organocatalytic system. On the basis of experimental results and spectroscopic
      analysis, such as UV/Vis, fluorescence emission (FL), NMR, and circular dichroism
      (CD) spectroscopy, as well as ESI-MS, we found that the molecular assembly of
      phosphine and primary amine played a crucial role in this enantioselective
      reaction, in which a possible supramolecular complex was formed as an effective
      chiral catalyst through noncovalent molecular interactions of a cinchona alkaloid
      derived primary amine with triphenylphosphine.

PMID- 23554320
TI  - Impact of etanercept on work and activity impairment in employed moderate to
      severe rheumatoid arthritis patients in the United States.
AB  - OBJECTIVE: To quantify the impact of etanercept on work and activity impairment
      in employed US patients with moderate to severe rheumatoid arthritis (RA).
      METHODS: This prospective, observational, longitudinal study recruited RA
      patients initiating etanercept (50 mg/week) between January 2009 and March 2010.
      The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic
      productivity questionnaire were administered by telephone interviews at baseline
      and at 1, 2, 3, and 6 months after etanercept initiation. The human capital
      approach was used to estimate the costs of work impairment. Changes in WPAI
      measures were analyzed using Wilcoxon's signed rank test. RESULTS: RA patients (n
      = 204) initiating etanercept were a mean +/- SD age of 46.6 +/- 10.9 years and
      72% were women. After 6 months, 153 patients continued treatment (continuers) and
      showed significant decreases in overall work impairment (41.9% at baseline versus
      25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001),
      presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7%
      versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to
      RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity
      for continuers was 284.5 hours per patient, equating to $3,233-22,533 depending
      on annual income level, which partially or completely offset the annual cost of
      etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to
      69.6% at 6 months (P < 0.0001). CONCLUSION: In US employed moderate to severe RA
      patients, etanercept led to significant reductions in overall work and activity
      impairment; the value of increased work productivity partially or completely
      offset the cost of treatment.

PMID- 23554321
TI  - Identification of novel sesterterpene/triterpene synthase from Bacillus clausii.
AB  - Basic enzyme: The tetraprenyl-beta-curcumene synthase homologue from the
      alkalophilic Bacillus clausii catalyses conversions of a geranylfarnesyl
      diphosphate and a hexaprenyl diphosphate into novel head-to-tail acyclic
      sesterterpene and triterpene. Tetraprenyl-beta-curcumene synthase homologues
      represent a new family of terpene synthases that form not only sesquarterpene but
      also sesterterpene and triterpene.

PMID- 23554323
TI  - Reviewer list for Birth Defects Research Part A in 2012.

PMID- 23554322
TI  - Sub-functionalization of duplicated genes in the evolution of nine-spined
      stickleback hatching enzyme.
AB  - Gene duplication is the primary source of novel genes, and is followed by non-,
      sub-, or neo-functionalization. In this study, we compared the egg envelope
      digestion mechanism of hatching enzymes between three-spined stickleback and nine
      spined stickleback species, and found that the function of the hatching enzymes
      of nine-spined sticklebacks was uniquely derived by gene duplication, followed by
      sub-functionalization. The hatching enzyme of euteleosts consists of two
      metalloproteases, high choriolytic enzyme (HCE), and low choriolytic enzyme
      (LCE). LCE, especially, has an important role in solubilizing egg envelope
      protein by cleaving two specific sites. Three-spined stickleback had a single
      copy of the LCE gene, like other euteleosts. However, nine-spined stickleback had
      two types of LCE genes, alpha-type and beta-type, suggesting that a duplication
      of the LCE gene occurred during the evolution of sticklebacks. The alpha-type and
      beta-type each cleaved one of the two sites. Therefore, in the nine-spined
      stickleback, the function of the ancestral LCE was driven by a single copy gene,
      which was partitioned into two functions separately driven by two duplicated
      genes, and egg envelope was solubilized by the cooperative action of the two
      LCEs, alpha-type and beta-type. Herein, we provide a molecular mechanism for an
      evolutionary adaptation driven by gene duplication and sub-functionalization.

PMID- 23554324
TI  - Seeing two-dimensional sheets on arbitrary substrates by fluorescence quenching
      microscopy.
AB  - Fluorescence quenching microscopy (FQM) is demonstrated as a low-cost and high
      throughput technique for seeing graphene-like 2D sheets such as MoS2 . FQM
      provides high contrast and layer resolution comparable to those of scanning
      electron microscopy, but allows the imaging of samples deposited on arbitrary
      substrates, including non-conductive substrates such as quartz. Solution
      fluorescence quenching studies suggest that FQM should be feasible for many other
      2D materials such as WS2 , Bi2 Te3 , MoSe2 , NbSe2 , and TaS2 . 

PMID- 23554325
TI  - Three-dimensional pore structure analysis of polycaprolactone nano-microfibrous
      scaffolds using theoretical and experimental approaches.
AB  - In this article the pore structure and porosity parameters of polycaprolactone
      (PCL) nano-microfibrous scaffolds are investigated using a predicting theoretical
      model and a nondestructive evaluation approach based on confocal laser scanning
      microscopy (CLSM) and three-dimensional image analysis. Different fibrous
      scaffolds with different fiber diameters produced by electrospinning process and
      their 3D-pore structure were evaluated theoretically and also compared to results
      of CLSM and capillary flow porometery methods. The effect of polymer
      concentration on the pore structure of scaffolds was also investigated. The
      results showed that, the introduced approach not only can measure the pore size
      distribution of nanofibrous scaffolds, but also can measure pore
      interconnectivity of fibrous scaffolds. Furthermore, the results showed that
      increasing the fiber diameter resulted from increasing the polymer concentration
      in solvent can effectively increase the pore dimensions within the scaffold
      structure.

PMID- 23554326
TI  - Toward a quantitative understanding of the Wnt/beta-catenin pathway through
      simulation and experiment.
AB  - Wnt signaling regulates cell survival, proliferation, and differentiation
      throughout development and is aberrantly regulated in cancer. The pathway is
      activated when Wnt ligands bind to specific receptors on the cell surface,
      resulting in the stabilization and nuclear accumulation of the transcriptional co
      activator beta-catenin. Mathematical and computational models have been used to
      study the spatial and temporal regulation of the Wnt/beta-catenin pathway and to
      investigate the functional impact of mutations in key components. Such models
      range in complexity, from time-dependent, ordinary differential equations that
      describe the biochemical interactions between key pathway components within a
      single cell, to complex, multiscale models that incorporate the role of the
      Wnt/beta-catenin pathway target genes in tissue homeostasis and carcinogenesis.
      This review aims to summarize recent progress in mathematical modeling of the Wnt
      pathway and to highlight new biological results that could form the basis for
      future theoretical investigations designed to increase the utility of theoretical
      models of Wnt signaling in the biomedical arena.

PMID- 23554327
TI  - Osteogenic differentiation of human bone marrow mesenchymal stem cells in
      hydrogel containing nacre powder.
AB  - Nacre (or mother of pearl) can facilitate bone cell differentiation and can speed
      up their mineralization. Here we report on the capability of nacre to induce
      differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) and the
      production of extracellular matrix. hBM-MSCs were encapsulated in an alginate
      hydrogel containing different concentrations of powdered nacre and cultured in
      the same environment until Day 28. Analysis of osteogenic gene expression,
      histochemistry, second harmonic generation (SHG) microscopy, and Raman scattering
      spectroscopy were used to characterize the synthesis of the extracellular matrix.
      In the presence of nacre powder, a significant increase in matrix synthesis from
      D21 in comparison with pure alginate was observed. Histochemistry revealed the
      formation of a new tissue composed of collagen fibers in the presence of nacre
      (immunostaining and SHG), and hydroxyapatite crystals (Raman) in the alginate
      beads. These results suggest that nacre is efficient in hBM-MSCs differentiation,
      extracellular matrix production and mineralization in alginate 3D biomaterials.

PMID- 23554328
TI  - A comprehensive microscopic picture of the benzhydryl radical and cation
      photogeneration and interconversion through electron transfer.
AB  - Bond cleavage and bond formation are central to organic chemistry. Carbocations
      play a key role in our understanding of nucleophilic substitution reactions that
      involve both processes. The precise understanding of the mechanism and dynamics
      of the photogeneration of carbocations and carbon radicals is therefore an
      important quest. In particular, the role of electron transfer for the generation
      of carbocations from the radical pair is still unclear. A quantitative
      femtosecond absorption study is presented, with ultrabroad probing on selected
      donor and acceptor substituted benzhydryl chlorides irradiated with 270 nm (35
      fs) pulses. The ultrafast bond cleavage within 300 fs is almost exclusively
      homolytic, thus leading to a radical pair. The carbocations observable in the
      nanosecond regime are generated from these radicals by electron transfer from the
      benzhydryl to the chlorine radical within the first tens of picoseconds. Their
      concentration is reduced by geminate recombination within hundreds of
      picoseconds. In moderately polar solvents this depletion almost extinguishes the
      cation population; in highly polar solvents free ions are still observable on the
      nanosecond timescale. The explanation of the experimental findings requires the
      microscopic realm of the intermediates to be accounted for, including their
      spatial and environmental distributions. The distance dependent electron transfer
      described by Marcus theory is combined with Smoluchowski diffusion. The depletion
      of the radical pair distribution at small distances causes a temporal increase of
      the mean distance and the observed stretched exponential electron transfer. A
      close accord with experiment can only be reached for a broad distribution of the
      nascent radical pairs. The increase in the inter-radical and inter-ion pair
      distance is measured directly as a shift of the UV/Vis absorption of the
      products. The results demonstrate that, at least for aprotic solvents,
      traditional descriptions of reaction mechanisms based on the concept of contact
      and solvent-separated pairs have to be reassessed.

PMID- 23554329
TI  - Hierarchical hollow hydroxyapatite microspheres: microwave-assisted rapid
      synthesis by using pyridoxal-5'-phosphate as a phosphorus source and application
      in drug delivery.
AB  - Three-dimensional (3D) hydroxyapatite (HAP) hierarchical nanostructures, in
      particular hollow nanostructures, have attracted much attention owing to their
      potential applications in many biomedical fields. Herein, we report a rapid
      microwave-assisted hydrothermal synthesis of a variety of hydroxyapatite
      hierarchical nanostructures that are constructed by the self-assembly of nanorods
      or nanosheets as the building blocks, including HAP nanorod-assembled
      hierarchical hollow microspheres (HA-NRHMs), HAP nanorod-assembled hierarchical
      microspheres (HA-NRMs), and HAP nanosheet-assembled hierarchical microspheres (HA
      NSMs) by using biocompatible biomolecule pyridoxal-5'-phosphate (PLP) as a new
      organic phosphorus source. The PLP molecules hydrolyze to produce phosphate ions
      under microwave-hydrothermal conditions, and the phosphate ions react with
      calcium ions to form HAP nanorods or nanosheets; then, these nanorods or
      nanosheets self-assemble to form 3D HAP hierarchical nanostructures. The
      preparation method reported herein is time-saving, with microwave heating times
      as short as 5 min. The HA-NRHMs consist of HAP nanorods as the building units,
      with an average diameter of about 50 nm. The effects of the experimental
      conditions on the morphology and crystal phase of the products are investigated.
      The hydrolysis of PLP under microwave-hydrothermal conditions and the important
      role of PLP in the formation of 3D HAP hierarchical nanostructures are
      investigated and a possible formation mechanism is proposed. The products are
      explored for potential applications in protein adsorption and drug delivery. Our
      experimental results indicate that the HA-NRHMs have high drug/protein-loading
      capacity and sustained drug-release behavior. Thus, the as-prepared HA-NRHMs are
      promising for applications in drug delivery and protein adsorption.

PMID- 23554330
TI  - Liquid-mediated three-dimensional scanning probe nanosculpting.
AB  - 3D functional polymer brushes are fabricated by liquid-mediated scanning probe
      nanosculpting (LSPN). Surface-tethered functional polymer brushes, which are
      immersed in their good solvent, are mechanically cleaved away from the substrate
      by the AFM tip at high forces, and immediately imaged in situ with the same AFM
      tip at low applied forces. 

PMID- 23554331
TI  - Two pear accessions evaluated for susceptibility to pear psylla Cacopsylla bidens
      (Sulc) in Israel.
AB  - BACKGROUND: The pear psylla, Cacopsylla bidens (Sulc), is one of the most
      damaging pests of commercial pear orchards in Israel. Psylla control is a major
      obstacle to efficient integrated pest management, necessitating research on
      cultivars with natural resistance to pear psylla. Recently, two pear accessions
      (Py.760-261 and Py.701-202) from the local Newe Ya'ar fruit tree live collection
      were identified as having apparent resistance to pear psylla. Our goal was to
      evaluate the resistance of these two accessions relative to the commercial
      cultivar Spadona Estiva, and to identify whether the resistance mechanisms in the
      former interfere with insect colonisation of the plant (antixenosis) or inhibit
      insect growth, development, reproduction and survival (antibiosis). RESULTS:
      Settlement and development of C. bidens was evaluated under natural conditions
      (pear orchard), semi-natural conditions (potted plants), and on detached branches
      and leaves (laboratory). Our results indicate that the selection Py.760-261 is 10
      times more resistant than Spadona while Py.701-202 is five times more resistant.
      CONCLUSIONS: The resistance mechanism in both accessions appears to be antibiosis
      affecting nymph survival. These resistant accessions may be used as rootstock or
      as a source of resistant genes in breeding programmes.

PMID- 23554332
TI  - Understanding CO2 dynamics in metal-organic frameworks with open metal sites.

PMID- 23554333
TI  - Prevention of glucocorticoid-induced fractures: which patients should we treat?
      Comment on the article by Grossman et al.

PMID- 23554335
TI  - Vibrational sum-frequency generation activity of a 2,4-dinitrophenyl phospholipid
      hybrid bilayer: retrieving orientational parameters from a DFT analysis of
      experimental data.
AB  - The vibrational nonlinear activity of films of 2,4-dinitrophenyl phospholipid
      (DNP) at the solid interface is measured by sum-frequency generation spectroscopy
      (SFG). Hybrid bilayers are formed by a Langmuir-Schaefer approach in which the
      lipid layer is physisorbed on top of a self-assembled monolayer of dodecanethiol
      on Pt with the polar heads pointing out from the surface. The SFG response is
      investigated in two vibrational frequency domains, namely, 3050-2750 and 1375
      1240 cm(-1). The first region probes the CH stretching modes of DNP films, and
      the latter explores the vibrational nonlinear activity of the 2,4-dinitroaniline
      moiety of the polar head of the lipid. Analysis of the CH stretching vibrations
      suggests substantial conformational order of the aliphatic chains with only a few
      gauche defects. To reliably assign the detected SFG signals to specific molecular
      vibrations, DFT calculations of the IR and Raman activities of molecular models
      are performed and compared to experimental solid-state spectra. This allows
      unambiguous assignment of the observed SFG vibrations to molecular modes
      localized on the 2,4-dinitroaniline moiety of the polar head of DNP. Then, SFG
      spectra of DNP in the 1375-1240 cm(-1) frequency range are simulated and compared
      with experimental ones, and thus the 1,4-axis of the 2,4-dinitrophenyl head is
      estimated to have tilt and rotation angles of 45+/-5 degrees  and 0+/-30 degrees
      , respectively.

PMID- 23554334
TI  - Preparation of polycaprolactone microspheres-aggregated scaffold with ultra big
      pores and fuzzy sphere surface by a one-step phase separation method.
AB  - A microspheres-aggregated scaffold with ultra big pores (over 300 MUm) and fuzzy
      microspheres is fabricated by incubating polycaprolactone (PCL)/tetrahydrofuran
      (THF) solution in a -20 degrees C refrigerator, following by freeze-drying.
      Formation of the scaffold is mainly governed by the crystallization of the PCL
      polymer at appropriate conditions. All the 10-20% PCL/THF solutions yield the
      microspheres-aggregated scaffolds when the initial solution temperature is higher
      than 37 degrees C, whereas the 10-15% solutions form dense membranes when the
      initial solution temperature is below 25 degrees C. The size of the microspheres
      and pores is as large as 70-150 MUm and 170-816 MUm, respectively. The PCL
      microspheres-aggregated scaffold can better support the adhesion and
      proliferation of bone marrow mesenchymal stem cells (BMSCs) compared to the
      traditional porous scaffold obtained by a porogen leaching method. The tendencies
      of chondrogenesis and osteogenesis differentiation of BMSCs are observed on the
      microspheres-aggregated scaffold and the ordinary porous scaffold, respectively.

PMID- 23554336
TI  - Highly enantioselective hydrogenation of 2,4-diaryl-1,5-benzodiazepines catalyzed
      by dendritic phosphinooxazoline iridium complexes.
AB  - A PHOX with arms: A series of dendrimers with Ir phosphinooxazoline (PHOX) cores
      were designed and synthesized and found to be highly effective and recoverable
      catalysts for asymmetric hydrogenation of 2,4-diaryl-1,5-benzodiazepines. An
      obvious positive dendritic effect on reactivity was observed, leading to chiral
      nitrogen-containing heterocycles with excellent enantioselectivities.

PMID- 23554337
TI  - Biomolecular identification of beta-defensin-like peptides from the skin of the
      soft-shelled turtle Apalone spinifera.
AB  - Numerous bacteria are frequently observed in the superficial corneocytes forming
      the corneous layer of the soft-shelled turtle Apalona spinifera. The resistance
      to bacterial penetration through the living epidermis in this turtle suggests the
      presence of an antimicrobial barrier, possibly derived from the presence of anti
      microbial peptides in the epidermis. Four beta-defensin-like peptides, named As
      BD-1 to 4, have been characterized from skin tissues using molecular and
      bioinformatics methods. The precursor peptides contain the beta-defensin motif
      with the typical cysteine localization pattern. The analysis of the expression
      for the four different beta-defensin-like proteins show that these molecules are
      expressed in the skin (epidermis and dermis) of the carapace, neck, digit, and
      tail but are apparently not expressed in the liver or intestine under normal
      conditions. These data suggest that in the skin of the soft-shelled turtle there
      are potential effective anti-microbial peptides against epidermal bacteria.

PMID- 23554338
TI  - Shaping functional nano-objects by 3D confined supramolecular assembly.
AB  - Nano-objects are generated through 3D confined supramolecular assembly, followed
      by a sequential disintegration by rupturing the hydrogen bonding. The shape of
      the nano-objects is tunable, ranging from nano-disc, nano-cup, to nano-toroid.
      The nano-objects are pH-responsive. Functional materials for example inorganic or
      metal nanoparticles are easily complexed onto the external surface, to extend
      both composition and microstructure of the nano-objects. 

PMID- 23554339
TI  - Effects of termiticide exposure on mutual interactions between the treated and
      untreated workers of the Asian subterranean termite Coptotermes gestroi.
AB  - BACKGROUND: Mutual interactions, including reciprocal food sharing and grooming
      between chlorantraniliprole- and fipronil-treated, and untreated Asian
      subterranean termites, Coptotermes gestroi (Wasmann), were examined using
      rubidium as a tracer. Two questions were addressed in this study: (1) After
      insecticide treatment, does the mutual interaction between termiticide-treated
      termites and untreated nestmates increase? (2) Does the nutritional status of
      both termiticide-treated termites and untreated nestmates affect the mutual
      interaction? RESULTS: The comparative data suggested that chlorantraniliprole
      treated termites were more regularly attended by untreated termites than the
      fipronil-treated termites. Mutual interaction between the chlorantraniliprole
      treated termites and untreated termites was not affected by their nutritional
      status. A high level of rubidium was present in the reciprocal exchange from
      fipronil-treated termites to starved untreated termites, indicating that
      intoxication induced alimentary or anal fluids served as a food source for
      starved termites. CONCLUSION: The results of the present study indicated that
      termites exposed to chlorantraniliprole were more likely to cease feeding and
      then undergo starvation. Thus, the treated termites were subject to intensive
      reciprocal food exchange and frequent attention from untreated nestmates. In the
      fipronil treatment, starvation status facilitated the reciprocal food exchange
      rate from treated termites to starved untreated termites.

PMID- 23554340
TI  - Effect of obesity onset on pendular energy transduction at spontaneous walking
      speed: Prader-Willi versus nonsyndromal obese individuals.
AB  - OBJECTIVE: To compare the mechanical external work (Wext ) and pendular energy
      transduction (Rstep ) at spontaneous walking speed (Ss ) in individuals with
      Prader-Willi syndrome (PWS) versus subjects with nonsyndromal obesity (OB) to
      investigate whether the early onset of obesity allows PWS subjects to adopt
      energy conserving gait mechanics. DESIGN AND METHODS: Wext and Rstep were
      computed using kinematic data acquired by an optoelectronic system and compared
      in 15 PWS (BMI = 39.5 +/- 1.8 kg m(-2) ; 26.7 +/- 1.5 year) and 15 OB (BMI = 39.3
      +/- 1.0 kg m(-2) ; 28.7 +/- 1.9 year) adults matched for gender, age and BMI and
      walking at Ss . RESULTS: Ss was significantly lower in PWS (0.98 +/- 0.03 m s(-1)
      ) than in OB (1.20 +/- 0.02 m s(-1) ; P < 0.001). There were no significant
      differences in Wext per kilogram between groups (PWS: 0.37 +/- 0.04 J kg(-1) m(
      1) ; OB: 0.40 +/- 0.05 J kg(-1) m(-1) ; P = 0.66) and in Rstep (PWS: 69.9 +/-
      2.9%; OB: 67.7 +/- 2.4%; P = 0.56). However, Rstep normalized to Froude number
      (Rstep /Fr) was significantly greater in PWS (6.0 +/- 0.6) than in OB (3.8 +/-
      0.2; P = 0.001). Moreover, Rstep /Fr was inversely correlated with age of obesity
      onset (r = -0.49; P = 0.006) and positively correlated with obesity duration (r =
      0.38; P = 0.036). CONCLUSION: Individuals with PWS seem to alter their gait to
      improve pendular energy transduction as a result of precocious and chronic
      adaptation to loading.

PMID- 23554341
TI  - Therapeutic options in anti-jo-1 antisynthetase syndrome with interstitial lung
      disease: comment on the article by Marie et al.

PMID- 23554342
TI  - New concept for a regenerative and resorbable prosthesis for tendon and ligament:
      physicochemical and biological characterization of PLA-braided biomaterial.
AB  - We present a concept for a new regenerative and resorbable prosthesis for tendon
      and ligament and characterize the physicomechanical and biological behavior of
      one of its components, a hollow braid made of poly-lactide acid (PLA) which is
      the load-bearing part of the prosthesis concept. The prosthesis consists of a
      braid, microparticles in its interior serving as cell carriers, and a surface non
      adherent coating, all these parts being made of biodegradable materials. The PLA
      braid has a nonlinear convex stress-strain behavior with a Young modulus of 1370
      +/- 90 MPa in the linear, stretched state, and after 12 months of hydrolytic
      degradation the modulus shows a reduction by a factor of four. Different
      disinfection methods were tested as to their efficiency in cleansing the braid
      and preparing it for cell culture. Fibroblasts of L929 line were grown on the PLA
      braid for 14 days, showing good adherence and proliferation. These studies
      validate the PLA braid for the intended purpose in the regenerative prosthesis
      concept.

PMID- 23554343
TI  - Dispersion of graphene sheets in aqueous solution by oligodeoxynucleotides.
AB  - Applications of graphene sheets in the fields of biosensors and biomedical
      devices are limited by their insolubility in water. Consequently, understanding
      the dispersion mechanism of graphene in water and exploring an effective way to
      prepare stable dispersions of graphene sheets in water is of vital importance for
      their application in biomaterials, biosensors, biomedical devices, and drug
      delivery. Herein, a method for stable dispersion of graphene sheets in water by
      single-stranded oligodeoxynucleotides (ssODNs) is studied. Owing to van der Waals
      interactions between graphene sheets, they undergo layer-to-layer (LtL)
      aggregation in water. Molecular dynamics simulations show that, by disrupting van
      der Waals interaction of graphene sheets with ssODNs, LtL aggregation of graphene
      sheets is prevented, and water molecules can be distributed stably between
      graphene sheets. Thus, graphene sheets are dispersed stably in water in the
      presence of ssODNs. The effects of size and molarity of ssODNs and noncovalent
      modification of graphene sheets are also discussed.

PMID- 23554344
TI  - Highly comparative time-series analysis: the empirical structure of time series
      and their methods.
AB  - The process of collecting and organizing sets of observations represents a common
      theme throughout the history of science. However, despite the ubiquity of
      scientists measuring, recording and analysing the dynamics of different
      processes, an extensive organization of scientific time-series data and analysis
      methods has never been performed. Addressing this, annotated collections of over
      35 000 real-world and model-generated time series, and over 9000 time-series
      analysis algorithms are analysed in this work. We introduce reduced
      representations of both time series, in terms of their properties measured by
      diverse scientific methods, and of time-series analysis methods, in terms of
      their behaviour on empirical time series, and use them to organize these
      interdisciplinary resources. This new approach to comparing across diverse
      scientific data and methods allows us to organize time-series datasets
      automatically according to their properties, retrieve alternatives to particular
      analysis methods developed in other scientific disciplines and automate the
      selection of useful methods for time-series classification and regression tasks.
      The broad scientific utility of these tools is demonstrated on datasets of
      electroencephalograms, self-affine time series, heartbeat intervals, speech
      signals and others, in each case contributing novel analysis techniques to the
      existing literature. Highly comparative techniques that compare across an
      interdisciplinary literature can thus be used to guide more focused research in
      time-series analysis for applications across the scientific disciplines.

PMID- 23554345
TI  - A simple probabilistic model of submicroscopic diatom morphogenesis.
AB  - Unicellular algae called diatoms morph biomineral compounds into tough
      exoskeletons via complex intracellular processes about which there is much to be
      learned. These exoskeletons feature a rich variety of structures from
      submicroscale to milliscale, many that have not been reproduced in vitro. In
      order to help understand this complex miniature morphogenesis, here we introduce
      and analyse a simple model of biomineral kinetics, focusing on the exoskeleton's
      submicroscopic patterned planar structures called pore occlusions. The model
      reproduces most features of these pore occlusions by retuning just one parameter,
      thereby indicating what physio-biochemical mechanisms could sufficiently explain
      morphogenesis at the submicroscopic scale: it is sufficient to identify a
      mechanism of lateral negative feedback on the biomineral reaction kinetics. The
      model is nonlinear and stochastic; it is an extended version of the threshold
      voter model. Its mean-field equation provides a simple and, as far as the authors
      are aware, new way of mapping out the spatial patterns produced by lateral
      inhibition and variants thereof.

PMID- 23554346
TI  - The stubborn roots of metabolic cycles.
AB  - Efforts to catalogue the structure of metabolic networks have generated highly
      detailed, genome-scale atlases of biochemical reactions in the cell.
      Unfortunately, these atlases fall short of capturing the kinetic details of
      metabolic reactions, instead offering only topological information from which to
      make predictions. As a result, studies frequently consider the extent to which
      the topological structure of a metabolic network determines its dynamic
      behaviour, irrespective of kinetic details. Here, we study a class of metabolic
      networks known as non-autocatalytic metabolic cycles, and analytically prove an
      open conjecture regarding the stability of their steady states. Importantly, our
      results are invariant to the choice of kinetic parameters, rate laws, equilibrium
      fluxes and metabolite concentrations. Unexpectedly, our proof exposes an
      elementary but apparently open problem of locating the roots of a sum of two
      polynomials S = P + Q, when the roots of the summand polynomials P and Q are
      known. We derive two new results named the Stubborn Roots Theorems, which provide
      sufficient conditions under which the roots of S remain qualitatively identical
      to the roots of P. Our study illustrates how complementary feedback, from
      classical fields such as dynamical systems to biology and vice versa, can expose
      fundamental and potentially overlooked questions.

PMID- 23554347
TI  - Characterization of the interface between adsorbed fibronectin and human
      embryonic stem cells.
AB  - The cell-substrate interface plays a key role in the regulation of cell
      behaviour. Defining the properties of this interface is particularly important
      for human embryonic stem (hES) cell culture, because changes in this environment
      can regulate hES cell differentiation. It has been established that fibronectin
      coated surfaces can promote the attachment, growth and maintenance of the
      undifferentiated phenotype of hES cells. We investigated the influence of the
      surface density of adsorbed fibronectin on hES cell behaviour in defined serum
      free culture conditions and demonstrated that only 25 per cent surface saturation
      was required to maintain attachment, growth and maintenance of the
      undifferentiated phenotype. The influence of surface-adsorbed fibronectin
      fragments was compared with whole fibronectin, and it was demonstrated that the
      120 kDa fragment central binding domain alone was able to sustain hES cells in an
      undifferentiated phenotype in a similar fashion to fibronectin. Furthermore, hES
      cell attachment to both fibronectin and the 120 kDa fragment was mediated by
      integrin alpha5beta1. However, although a substrate-attached synthetic arginine
      glycine-aspartic acid (RGD) peptide alone was able to promote the attachment and
      spreading of fibroblasts, it was inactive for hES cells, indicating that stem
      cells have different requirements in order to attach and spread on the central
      fibronectin RGD-cell-binding domain. This study provides further information on
      the characteristics of the cell-substrate interface required to control hES cell
      behaviour in clearly defined serum-free conditions, which are needed for the
      development of therapeutic applications of hES cells.

PMID- 23554348
TI  - Preload-responsive adhesion: effects of aspect ratio, tip shape and alignment.
AB  - We tested the adhesive response of polymer surfaces structured with arrays of
      cylindrical fibrils having diameters of 10-20 um and aspect ratios 1-2.4. Fibrils
      had two different tip shapes of end-flaps and round edges. A preload-induced
      mechanical buckling instability of the fibrils was used to switch between the
      states of adhesion and non-adhesion. Non-adhesion in fibrils with round edges was
      reached at preloads that caused fibril buckling, whereas fibrils with end-flaps
      showed adhesion loss only at very high preloads. The round edge acted as a
      circumferential flaw prohibiting smooth tip contact recovery leading to an
      adhesion loss. In situ observations showed that, after reversal of buckling, the
      end-flaps unfold and re-form contact under prevailing compressive stress,
      retaining adhesion in spite of buckling. At very high preloads, however, end
      flaps are unable to re-form contact resulting in adhesion loss. Additionally, the
      end-flaps showed varying contact adaptability as a function of the fibril-probe
      alignment, which further affects the preload for adhesion loss. The combined
      influence of preload, tip shape and alignment on adhesion can be used to switch
      adhesion in bioinspired fibrillar arrays.

PMID- 23554349
TI  - Contact compliance effects in the frictional response of bioinspired fibrillar
      adhesives.
AB  - The shear failure and friction mechanisms of bioinspired adhesives consisting of
      elastomer arrays of microfibres terminated by mushroom-shaped tips are
      investigated in contact with a rigid lens. In order to reveal the interplay
      between the vertical and lateral loading directions, experiments are carried out
      using a custom friction set-up in which normal stiffness can be made either high
      or low when compared with the stiffness of the contact between the fibrillar
      adhesive and the lens. Using in situ contact imaging, the shear failure of the
      adhesive is found to involve two successive mechanisms: (i) cavitation and
      peeling at the contact interface between the mushroom-shaped fibre tip endings
      and the lens; and (ii) side re-adhesion of the fibre's stem to the lens. The
      extent of these mechanisms and their implications regarding static friction
      forces is found to depend on the crosstalk between the normal and lateral loading
      directions that can result in contact instabilities associated with fibre
      buckling. In addition, the effects of the viscoelastic behaviour of the
      polyurethane material on the rate dependence of the shear response of the
      adhesive are accounted for.

PMID- 23554350
TI  - Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine
      (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues.
AB  - Classic examples of psychoactive arylcycloalkylamines include ketamine and 1-(1
      phenylcyclohexyl)piperidine (PCP) and many others serve as important structural
      templates for neuropharmacological research. The recent emergence of PCP
      analogues that can be obtained from internet retailers requires the
      implementation of appropriate monitoring strategies for harm reduction purposes.
      Access to analytical data plays a key part when encountering these substances,
      especially if reference material is not available. The present study describes
      the synthesis of three substituted 1-(1-phenylcyclohexyl)piperidines, (3-MeO-, 4
      MeO- and 3-Me-PCP) and three substituted 1-(1-phenylcyclohexyl)pyrrolidine
      analogues (3-MeO-, 4-MeO- and 3-Me-PCPy). Analytical characterizations of all six
      arylcyclohexylamines and their primary 1-phenylcyclohexanamine intermediates
      included gas chromatography ion trap electron- and chemical ionization and high
      resolution mass spectrometry, liquid chromatography electrospray hybrid triple
      quadrupole linear ion trap tandem mass spectrometry, infrared, diode array
      detection and (1) H and (13) C nuclear magnetic resonance (NMR) spectroscopy.
      Solvent (CDCl3 vs. d6 -DMSO) and protonation effects (free bases vs hydrochloride
      salts) were studied in order to investigate the impact on shifts and splitting
      patterns, for example, when attempting to assign separate axial and equatorial
      proton chemical shifts of NMR spectra. Differentiation between the isomeric 3-MeO
      /4-MeO-PCP and PCPy analogues was feasible under mass spectral conditions. Gas
      chromatography analysis appeared to induce notable degradation of the 4-MeO
      substituted analytes, especially when dealing with the HCl salts which led to the
      detection of the substituted 1-phenylcyclohex-1-ene nucleus. This phenomenon was
      observed to be less pronounced with the 3-MeO isomers, possibly due to the
      resonance properties of the para-methoxy group followed by more facile
      elimination of the amine.

PMID- 23554351
TI  - Organic and organometallic nanofibers formed by supramolecular assembly of
      diamond-shaped macrocyclic ligands and Pd(II) complexes.
AB  - Stacked rings: A diamond-shaped macrocycle with two inward phenanthroline ligands
      and outward long alkyl chains, and its Pd(II) complex form organic and
      organometallic fibrous aggregates, respectively, as revealed by NMR, UV/Vis, AFM,
      and TEM measurements. The most likely structures are face-to-face stacked
      macrocycles, generating nanotubes. 

PMID- 23554352
TI  - Development of a checklist of safe discharge practices for hospital patients.
AB  - BACKGROUND: Discharge from hospital can be a vulnerable period for patients.
      Multifaceted "discharge bundles" facilitate care transitions and possibly
      decrease adverse outcomes. We describe a structured approach to discharge
      planning, starting from admission and proceeding through discharge, using a
      standardized checklist of tasks to be performed for each hospitalization day.
      OBJECTIVE: To create an evidence-based checklist of safe discharge practices for
      hospital patients. METHODS: In the province of Ontario, the Ministry of Health
      and Long-Term Care convened a panel of expert members from multiple disciplines
      and across several healthcare sectors. The panel conducted a systematic search of
      the literature and used a structured approach to review evidence-based practices
      that ensure efficient, effective, safe, and patient-centered care transitions. A
      discharge-checklist tool was created to facilitate safe discharge from hospital.
      RESULTS: The final checklist describes the processes necessary for a safe and
      optimal discharge and recommended timeline of when to complete each step,
      starting from the first day of admission. The checklist domains include (1)
      indication for hospitalization, (2) primary care, (3) medication safety, (4)
      follow-up plans, (5) home-care referral, (6) communication with outpatient
      providers, and (7) patient education. CONCLUSIONS: The Checklist of Safe
      Discharge Practices for Hospital Patients summarizes the sequence of events that
      need to be completed throughout a typical hospitalization. Standardizing
      discharge planning and initiating processes early on in a patient's hospital stay
      may ensure a safe transition home.

PMID- 23554353
TI  - Blunted metabolic responses to cold and insulin stimulation in brown adipose
      tissue of obese humans.
AB  - OBJECTIVE: Inactive brown adipose tissue (BAT) may predispose to weight gain.
      This study was designed to measure metabolism in the BAT of obese humans, and to
      compare it to that in lean subjects. The impact of weight loss on BAT and the
      association of detectable BAT with various metabolic characteristics were also
      assessed. DESIGN AND METHODS: Using positron emission tomography (PET), cold- and
      insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean
      humans were quantified. Further, cold-induced glucose uptake was measured in
      obese subjects before and after a 5-month conventional weight loss. RESULTS: Mean
      responses in BAT glucose uptake rate to both cold and insulin stimulation were
      twice as large in lean as in obese subjects. Blood flow in BAT was also lower in
      obese subjects under cold conditions. The increase in cold-induced BAT glucose
      uptake rate after weight loss was not statistically significant. Subjects with
      cold-activated detectable BAT were leaner and had higher whole-body insulin
      sensitivity than BAT-negative subjects, irrespective of age and gender.
      CONCLUSIONS: The effects of cold and insulin on BAT activity are severely blunted
      in obesity, and the presence of detectable BAT may contribute to a metabolically
      healthy status.

PMID- 23554355
TI  - G protein-coupled estrogen receptor is apoptotic and correlates with increased
      distant disease-free survival of estrogen receptor-positive breast cancer
      patients.
AB  - PURPOSE: G protein-coupled estrogen receptor 1 (GPER1), previously named GPR30,
      is a membrane receptor reported to mediate nongenomic estrogen responses. We
      investigated if GPER1 expression correlates with any clinicopathologic variables
      and distant disease-free survival (DDFS) in patients with breast cancer, if any
      prognostic impact of the receptor is dependent on estrogen receptor-alpha (ER
      alpha) status, and if the receptor impacts apoptotic signaling in ER-positive
      breast cancer cells. EXPERIMENTAL DESIGN: GPER1 expression was analyzed by
      immunohistochemistry in breast tumors from 273 pre- and postmenopausal stage II
      patients, all treated with adjuvant tamoxifen for 2 years (cohort I) and from 208
      premenopausal lymph node-negative patients, of which 87% were not subjected to
      any adjuvant systemic treatment (cohort II). GPER1-dependent proapoptotic
      signaling was analyzed in MCF7 cells with and without GPER1 knockdown, T47D
      cells, HEK293 cells (HEK), and HEK stably expressing GPER1 (HEK-R). RESULTS:
      GPER1 positively correlates with ER and progesterone receptor expression.
      Multivariate analysis showed that GPER1 is an independent prognostic marker of
      increased 10-year DDFS in the ER-positive subgroup. HEK-R has higher basal
      proapoptotic signaling compared with HEK including increased cytochrome C
      release, caspase-3 cleavage, PARP cleavage, and decreased cell viability.
      Treating HEK-R with the proteasome inhibitor epoxomicin, to decrease GPER1
      degradation, further increases receptor-dependent proapoptotic signaling. Also,
      GPER1 knockdown decreases basal and agonist-stimulated proapoptotic receptor
      signaling in MCF7 cells. CONCLUSIONS: GPER1 is a prognostic indicator for
      increased DDFS in ER-positive breast cancer, which may be associated with
      constitutive GPER1-dependent proapoptotic signaling in ER-positive breast cancer
      cells.

PMID- 23554357
TI  - Influence of the Li...pi Interaction on the H/X...pi Interactions in
      HOLi...C6H6...HOX/XOH (X=F, Cl, Br, I) complexes.
AB  - The influences of the Li...pi interaction of C6H6...LiOH on the H...pi
      interaction of C6H6...HOX (X=F, Cl, Br, I) and the X...pi interaction of
      C6H6...XOH (X=Cl, Br, I) are investigated by means of full electronic second
      order Moller-Plesset perturbation theory calculations and "quantum theory of
      atoms in molecules" (QTAIM) studies. The binding energies, binding distances,
      infrared vibrational frequencies, and electron densities at the bond critical
      points (BCPs) of the hydrogen bonds and halogen bonds prove that the addition of
      the Li...pi interaction to benzene weakens the H...pi and X...pi interactions.
      The influences of the Li...pi interaction on H...pi interactions are greater than
      those on X...pi interactions; the influences of the H...pi interactions on the
      Li...pi interaction are greater than X...pi interactions on Li...pi interaction.
      The greater the influence of Li...pi interaction on H/X...pi interactions, the
      greater the influences of H/X...pi interactions on Li...pi interaction. QTAIM
      studies show that the intermolecular interactions of C6H6...HOX and C6H6...XOH
      are mainly of the pi type. The electron densities at the BCPs of hydrogen bonds
      and halogen bonds decrease on going from bimolecular complexes to termolecular
      complexes, and the pi-electron densities at the BCPs show the same pattern.
      Natural bond orbital analyses show that the Li...pi interaction reduces electron
      transfer from C6 H6 to HOX and XOH.

PMID- 23554356
TI  - Bacterial cellulose nanofibrillar patch as a wound healing platform of tympanic
      membrane perforation.
AB  - Bacterial cellulose (BC)-based biomaterials on medical device platforms have
      gained significant interest for tissue-engineered scaffolds or engraftment
      materials in regenerative medicine. In particular, BC has an ultrafine and highly
      pure nanofibril network structure and can be used as an efficient wound-healing
      platform since cell migration into a wound site is strongly meditated by the
      structural properties of the extracellular matrix. Here, the fabrication of a
      nanofibrillar patch by using BC and its application as a new wound-healing
      platform for traumatic tympanic membrane (TM) perforation is reported. TM
      perforation is a very common clinical problem worldwide and presents as
      conductive hearing loss and chronic perforations. The BC nanofibrillar patch can
      be synthesized from Gluconacetobacter xylinus; it is found that the patch
      contained a network of nanofibrils and is transparent. The thickness of the BC
      nanofibrillar patch is found to be approximately 10.33 +/- 0.58 MUm, and the
      tensile strength and Young's modulus of the BC nanofibrillar patch are 11.85 +/-
      2.43 and 11.90 +/- 0.48 MPa, respectively, satisfying the requirements of an
      ideal wound-healing platform for TM regeneration. In vitro studies involving TM
      cells show that TM cell proliferation and migration are stimulated under the
      guidance of the BC nanofibrillar patch. In vivo animal studies demonstrate that
      the BC nanofibrillar patch promotes the rate of TM healing as well as aids in the
      recovery of TM function. These data demonstrate that the BC nanofibrillar patch
      is a useful wound-healing platform for TM perforation. 

PMID- 23554358
TI  - Case report of accidental poisoning with the tranquilizer xylazine and the
      anesthetic ketamine confirmed by qualitative and quantitative toxicological
      analysis using GC-MS and LC-MS(n.).

PMID- 23554359
TI  - Desulfonylation of tosyl amides through catalytic photoredox cleavage of N-S bond
      under visible-light irradiation.
AB  - All lit up: A novel and efficient desulfonylation method of tosyl amides has been
      developed by means of visible-light-promoted reductive cleavage of N-S bonds.
      This method has a broad substrate scope, good functional group tolerance, and
      excellent yields.

PMID- 23554360
TI  - Selectivity differences of water-soluble vitamins separated on hydrophilic
      interaction stationary phases.
AB  - In this study, the retention behavior and selectivity differences of water
      soluble vitamins were evaluated with three types of polar stationary phases (i.e.
      an underivatized silica phase, an amide phase, and an amino phase) operated in
      the hydrophilic interaction chromatographic mode with ESI mass spectrometric
      detection. The effects of mobile phase composition, including buffer pH and
      concentration, on the retention and selectivity of the vitamins were
      investigated. In all stationary phases, the neutral or weakly charged vitamins
      exhibited very weak retention under each of the pH conditions, while the acidic
      and more basic vitamins showed diverse retention behaviors. With the
      underivatized silica phase, increasing the salt concentration of the mobile phase
      resulted in enhanced retention of the acidic vitamins, but decreased retention of
      the basic vitamins. These observations thus signify the involvement of secondary
      mechanisms, such as electrostatic interaction in the retention of these analytes.
      Under optimized conditions, a baseline separation of all vitamins was achieved
      with excellent peak efficiency. In addition, the effects of water content in the
      sample on retention and peak efficiency were examined, with sample stacking
      effects observed when the injected sample contained a high amount of water.

PMID- 23554361
TI  - Additional thoughts regarding barebacking contradictions.

PMID- 23554362
TI  - Where to go with barebacking research.

PMID- 23554363
TI  - Composition-dependent protein secretion and integrin level of osteoblastic cell
      on calcium silicate cements.
AB  - The purpose of this study was to investigate the responses of the human
      osteosarcoma cell line MG63 to calcium silicate cements with different Si/Ca
      molar ratios and different surface roughness. In particular, the study evaluated
      integrin subunit levels, phosphor-focal adhesion kinase (pFAK) levels and protein
      production at the cell attachment stage. The results indicated that the surface
      roughness (variations within a factor of 10) of the cements did not play a
      prominent role in cell attachment and proliferation, but the effect of
      composition was highlighted. Increased pFAK and total integrin levels and
      promoted cell attachment and cell cycle progression were observed upon an
      increase in cement Si content. Cement with a higher Si content was beneficial for
      collagen Type I (COL I) adsorption, COL I secretion, and alphalibbeta3
      subintegrin expression, whereas cement with a higher Ca content increased
      fibronectin (FN) adsorption, FN secretion, and enhanced alphavbeta1 subintegrin
      levels. These results establish composition-dependent differences in integrin
      binding as a mechanism regulating cellular responses to biomaterial surfaces.

PMID- 23554364
TI  - Changes in hospitals' credentialing requirements for board certification from
      2005 to 2010.
AB  - OBJECTIVE: In 2005, we conducted a study of the prevalence of board certification
      requirements for hospital privileging and found that one-third of hospitals did
      not require pediatricians to be board certified. In 2010, the American Board of
      Pediatrics implemented the Maintenance of Certification (MOC) program. To examine
      changes in the policies of hospitals regarding requirements for board
      certification, we surveyed privileging personnel at hospitals across the country.
      STUDY DESIGN: Telephone survey between April 2010 and June 2010 of privileging
      personnel at a random sample of 220 hospitals. RESULTS: Of the 220 hospitals, 23
      were ineligible because they had no pediatricians on staff, and 26 hospitals
      refused to participate. The remaining 154 hospitals completed the survey,
      resulting in a 78% participation rate. Compared with our findings in 2005, in
      2010 a greater proportion of hospitals now require board certification for
      general pediatricians (80% vs 67%, P = 0.141) and pediatric subspecialists (86%
      vs 71%, P = 0.048). Among these hospitals, a larger proportion (24% vs 4%) now
      requires board certification for all pediatricians at the point of initial
      privileging. However, a greater proportion of hospitals reported that they make
      exceptions to their board certification policies (99% vs 41%). CONCLUSION: In the
      5 years since our previous study, a larger proportion of hospitals now require
      pediatricians to be board certified, although the proportion of hospitals that
      make exceptions to this policy has increased twofold. Hospitals appear to be
      incorporating the MOC program into their privileging policies.

PMID- 23554365
TI  - Clinical and adipocytokine changes after bariatric surgery in morbidly obese
      women.
AB  - OBJECTIVE: Recent studies report the effect of bariatric surgery on glycaemia
      control and prevention of type-2-diabetes in obese patients. This study is about
      the pathophysiological mechanisms associated to these changes. DESIGN AND
      METHODS: Circulating levels of receptors of tumor necrosis factor (TNF-RI, TNF
      RII), visfatin, high molecular weight (HMW) adiponectin, and C reactive protein
      (CRP) in 30 morbidly obese women (body mass index, BMI>40 kg/m(2) ) and 60 normal
      weight controls (BMI>25 kg/m(2) ) were analyzed. Morbidly obese were studied at
      three time-points: before surgery (baseline), and 6 and 12 months after. RESULTS:
      After surgery, the levels of TNF-RI, TNF-RII, visfatin, and CRP were
      significantly lower than its baseline levels, whereas HMW adiponectin was higher.
      Fasting glucose, insulin, and homeostasis model assessment of insulin resistance
      (HOMA2-IR) levels were markedly lower postoperatively. High density lipoproteins
      (HDL) moderately increased, and triglyceride levels had sharply decreased. The
      study of the predictive value of variables indicated that preoperative levels of
      TNF-RI and visfatin correlated positively with levels of glucose, insulin,
      glycosylated hemoglobin A1c, and HOMA2-IR postoperatively, whereas adiponectin
      levels correlated negatively. Baseline CRP levels negatively linked to HDL and
      TNF-RII positively to triglyceride. CONCLUSIONS: The preoperative profile with
      high levels of proinflammatory adipocytokines is linked to smaller improvements
      in glucose homeostasis and lipid factors. The use of a range of biomarkers may
      predict the level of metabolic changes following bariatric surgery.

PMID- 23554366
TI  - Rapid, guanosine 5'-diphosphate-induced, gelation of chitosan sponges as novel
      injectable scaffolds for soft tissue engineering and drug delivery applications.
AB  - Novel injectable chitosan sponges based on rapid ionic crosslinking using
      guanosine 5'-diphosphate are introduced. The rapid gelation, high water
      retention, desirable physicochemical properties, soft tissue-like mechanical
      properties, and excellent cytocompatibility make these injectable sponges
      promising candidates for tissue regeneration and drug delivery applications. 

PMID- 23554367
TI  - A novel l-isoleucine-4'-dioxygenase and l-isoleucine dihydroxylation cascade in
      Pantoea ananatis.
AB  - A unique operon structure has been identified in the genomes of several plant-
      and insect-associated bacteria. The distinguishing feature of this operon is the
      presence of tandem hilA and hilB genes encoding dioxygenases belonging to the
      PF13640 and PF10014 (BsmA) Pfam families, respectively. The genes encoding HilA
      and HilB from Pantoea ananatis AJ13355 were cloned and expressed in Escherichia
      coli. The culturing of E. coli cells expressing hilA (E. coli-HilA) or both hilA
      and hilB (E. coli-HilAB) in the presence of l-isoleucine resulted in the
      conversion of l-isoleucine into two novel biogenic compounds: l-4'-isoleucine and
      l-4,4'-dihydroxyisoleucine, respectively. In parallel, two novel enzymatic
      activities were detected in the crude cell lysates of the E. coli-HilA and E.
      coli-HilAB strains: l-isoleucine, 2-oxoglutarate: oxygen oxidoreductase (4'
      hydroxylating) (HilA) and l-4'-hydroxyisoleucine, 2-oxoglutarate: oxygen
      oxidoreductase (4-hydroxylating) (HilB), respectively. Two hypotheses regarding
      the physiological significance of C-4(4')-hydroxylation of l-isoleucine in
      bacteria are also discussed. According to first hypothesis, the l-isoleucine
      dihydroxylation cascade is involved in synthesis of dipeptide antibiotic in P.
      ananatis. Another unifying hypothesis is that the C-4(4')-hydroxylation of l
      isoleucine in bacteria could result in the synthesis of signal molecules
      belonging to two classes: 2(5H)-furanones and analogs of N-acyl homoserine
      lactone.

PMID- 23554373
TI  - Evaluation of a combined linear-nonlinear approach for column characterization
      using modern alkaline-stable columns as model.
AB  - This study investigates if deeper understanding is achieved when combining
      nonlinear and linear chromatographic column characterization methods. As test
      systems, two hybrid columns (Phenomenex Gemini-NX C18 and Kromasil Eternity C18)
      and one classic one (Kromasil-C18) were selected. The nonlinear methods were
      based on firm adsorption theory and involved determination of adsorption
      isotherms followed by calculations with a new numerical tool, adsorption energy
      distribution, on probe components at different pH values. The linear methods
      involved the hydrophobic subtraction model and selected probe components
      retention factors as a function of pH. The combined analysis indicated that both
      complementary and confirmative information can be achieved regarding the actual
      model systems.

PMID- 23554372
TI  - Biocompatibility of TiO2 nanotubes with different topographies.
AB  - The biological response of osteoblast cells to implant materials depends on the
      topography and physico-chemistry of the implant surface and this determines the
      cell behavior such as shaping, adhesion and proliferation, and finally the cell
      fate. In this study, titanium (Ti) was anodized to create different topographies
      of titania nanotubes (TNTs) to investigate the cell behavior to them. TNTs with
      and without a highly ordered nanoporous layer on their top surface were
      fabricated using two-step and one-step anodizing processes, respectively. The
      TNTs without a highly ordered nanoporous layer on the top surface exhibited a
      rougher surface, higher surface energy and better hydrophilicity than the TNTs
      with such a layer. Osteoblast-like cells (SaOS2) were used to assess the
      biocompatibility of the TNTs with different topographies in comparison to bare cp
      Ti. Results indicated that TNTs can enhance the proliferation and adhesion of
      osteoblast-like cells. TNTs without a highly ordered nanoporous layer exhibited
      better biocompatibility than the TNTs covered by such a nanoporous layer. Cell
      morphology observation using confocal microscopy and SEM indicated that SaOS2
      cells that were adhered to the TNTs without the highly ordered nanoporous layer
      showed the longest filopodia compared to TNTs with a highly ordered nanoporous
      layer and bare cp-Ti.

PMID- 23554374
TI  - Multispectral image analysis for algal biomass quantification.
AB  - This article reports a novel multispectral image processing technique for rapid,
      noninvasive quantification of biomass concentration in attached and suspended
      algae cultures. Monitoring the biomass concentration is critical for efficient
      production of biofuel feedstocks, food supplements, and bioactive chemicals.
      Particularly, noninvasive and rapid detection techniques can significantly aid in
      providing delay-free process control feedback in large-scale cultivation
      platforms. In this technique, three-band spectral images of Anabaena variabilis
      cultures were acquired and separated into their red, green, and blue components.
      A correlation between the magnitude of the green component and the areal biomass
      concentration was generated. The correlation predicted the biomass concentrations
      of independently prepared attached and suspended cultures with errors of 7 and
      15%, respectively, and the effect of varying lighting conditions and background
      color were investigated. This method can provide necessary feedback for dilution
      and harvesting strategies to maximize photosynthetic conversion efficiency in
      large-scale operation.

PMID- 23554376
TI  - The role of electrostatics and temperature on morphological transitions of
      hydrogel nanostructures self-assembled by peptide amphiphiles via molecular
      dynamics simulations.
AB  - Smart biomaterials that are self-assembled from peptide amphiphiles (PA) are
      known to undergo morphological transitions in response to specific physiological
      stimuli. The design of such customizable hydrogels is of significant interest due
      to their potential applications in tissue engineering, biomedical imaging, and
      drug delivery. Using a novel coarse-grained peptide/polymer model, which has been
      validated by comparison of equilibrium conformations from atomistic simulations,
      large-scale molecular dynamics simulations are performed to examine the
      spontaneous self-assembly process. Starting from initial random configurations,
      these simulations result in the formation of nanostructures of various sizes and
      shapes as a function of the electrostatics and temperature. At optimal
      conditions, the self-assembly mechanism for the formation of cylindrical
      nanofibers is deciphered involving a series of steps: (1) PA molecules quickly
      undergo micellization whose driving force is the hydrophobic interactions between
      alkyl tails; (2) neighboring peptide residues within a micelle engage in a slow
      ordering process that leads to the formation of beta-sheets exposing the
      hydrophobic core; (3) spherical micelles merge together through an end-to-end
      mechanism to form cylindrical nanofibers that exhibit high structural fidelity to
      the proposed structure based on experimental data. As the temperature and
      electrostatics vary, PA molecules undergo alternative kinetic mechanisms,
      resulting in the formation of a wide spectrum of nanostructures. A phase diagram
      in the electrostatics-temperature plane is constructed delineating regions of
      morphological transitions in response to external stimuli. 

PMID- 23554375
TI  - Body-mass index and mortality risk in U.S. blacks compared to whites.
AB  - OBJECTIVE: To compare body-mass index (BMI)-related mortality risk in U.S. Blacks
      vs. Whites as the relationship appears to differ across race/ethnicity groups.
      METHODS: Cross-sectional surveys of nationally representative samples of 11,934
      Blacks and 59,741 Whites aged 35-75 in the National Health Interview Survey from
      1997 to 2002 with no history of cardiovascular disease (CVD) or cancer were
      pooled. Mortality follow-up was available through 2006. BMI was calculated from
      self-reported height and weight. We used adjusted Cox regression analysis to
      adjust for potential confounders. RESULTS: Over 9 years of follow-up, there were
      4303 deaths (1205 among never smokers). Age-adjusted mortality rates were higher
      in Blacks compared to Whites at BMI < 25 kg/m2 and showed no increase at higher
      levels of BMI. In men, adjusted hazard ratios for all-cause death rose in a
      similar fashion across upper BMI quintiles in Blacks and Whites; in women,
      however, BMI was positively associated with mortality risk in Whites, but
      inversely associated in Blacks (P interaction = 0.01). Racial disparities were
      amplified in subsidiary analyses that introduced a 12-month lag for mortality or
      focused on CVD mortality. CONCLUSIONS: The relationship of elevated BMI to
      mortality appeared weaker in US Blacks than in Whites, especially among women.

PMID- 23554377
TI  - The effect of laser-treated titanium surface on human gingival fibroblast
      behavior.
AB  - Surface modification, as a means of enhancing soft tissue integration in titanium
      would have significant advantages including less marginal bone resorption,
      predictable esthetic outcome, improved soft tissue stability, and seal against
      bacterial leakage. The aim of this study was to evaluate the effects of laser
      roughened titanium surfaces on human gingival fibroblast (HGF) viability,
      proliferation, and adhesion. Titanium discs were ablated with impulse laser in
      four different patterns. Polished and sand-blasted titanium discs were used as
      control groups. Specimen surface properties were determined using optical
      profilometry and scanning electron microscopy. HGF behavior on modified surfaces
      was analyzed using cell adhesion, viability, proliferation, and ELISA assays.
      Results suggested that modified Ti surfaces did not affect the viability of HGFs
      and improved adhesion was measured in laser treatment groups after 24 h. However,
      proliferation study showed that the adsorbance of fibroblast cells after 72 h
      cultured on polished titanium was higher and comparable with that of control
      cells. As for focal adhesion kinase (FAK), cells grown on laser modified surfaces
      had higher expression of FAK as compared with polished titanium. In conclusion,
      tested laser-treated surfaces seem to favor HGF adhesion. There were no
      significant differences between different laser treatment groups.

PMID- 23554378
TI  - CD133+ hematopoietic progenitor cells harbor HIV genomes in a subset of optimally
      treated people with long-term viral suppression.
AB  - BACKGROUND: Hematopoietic progenitor cells (HPCs) in the bone marrow of human
      immunodeficiency virus (HIV)-infected individuals have been proposed as a
      persistent reservoir of virus. However, some studies have suggested that HIV
      genomes detected in HPCs arise from T-cell contamination. METHODS: CD133-sorted
      HPCs and CD133-depleted bone marrow cells were purified from bone marrow
      specimens obtained from 11 antiretroviral-treated donors in whom the HIV load had
      been <48 copies/mL for at least 6 months. CD133 and CD3 expression on the cells
      was assessed by flow cytometry. HIV DNA was quantified by real-time polymerase
      chain reaction analysis. RESULTS: HIV genomes were detected in CD133-sorted
      samples from 6 donors, including 2 in whom viral loads were undetectable for >8
      years. CD3(+) T cells represented <1% of cells in all CD133-sorted samples. For 5
      of 6 CD133-sorted samples with detectable HIV DNA, the HIV genomes could not be
      explained by contaminating CD3(+) T cells. Donors with detectable HIV DNA in HPCs
      received their diagnosis significantly more recently than the remaining donors
      but had had undetectable viral loads for similar periods. CONCLUSIONS: HIV
      genomes can be detected in CD133-sorted cells from a subset of donors with long
      term viral suppression and, in most cases, cannot be explained by contamination
      with CD3(+) T cells.

PMID- 23554379
TI  - Hematopoietic stem cells and HIV infection.

PMID- 23554380
TI  - Separation of nonfucosylated antibodies with immobilized FcgammaRIII receptors.
AB  - Post-translational modifications can dramatically impact protein activity, but
      identifying such structure:function relationships, as well as capitalizing on
      functionally enhanced variants, is a significant challenge. Here, affinity
      chromatography resins that contained immobilized FcgammaRIII receptors were used
      to enrich nonfucosylated antibodies 6- to 9-fold, offering what may be a
      tractable method for both the identification of post-translational modifications
      that affect function, as well as a means to enrich variants with enhanced
      activity.

PMID- 23554381
TI  - Abstracts of the American Society of Andrology 38th Annual Meeting. April 13-16,
      2013. San Antonio, Texas, USA.

PMID- 23554382
TI  - The cost-effectiveness of a successful community-based obesity prevention
      program: the be active eat well program.
AB  - OBJECTIVE: To examine the cost-effectiveness of Be Active Eat Well (BAEW), a
      large, multifaceted, community-based capacity-building demonstration program that
      promoted healthy eating and physical activity for Australian children aged 4-12
      years between 2003 and 2006. DESIGN AND METHODS: A quasi-experimental,
      longitudinal design was used with anthropometric data collected at baseline (1001
      children-intervention; 1183-comparator) and follow-up. A societal perspective was
      employed, with intervention resource use measured retrospectively based on
      process evaluation reports, school newsletters, reports, and key stakeholder
      interviews, and valued in 2006 Australian dollars (AUD). Outcomes were measured
      as Body Mass Index (BMI) units saved and Disability Adjusted Life Years (DALYs)
      averted over the predicted cohort lifetime, and reported as incremental cost
      effectiveness ratios (with 95% uncertainty intervals). RESULTS: The intervention
      cost AUD0.34M ($0.31M; $0.38M) annually, and resulted in savings of 547 (-104;
      1209) BMI units and 10.2 (-0.19; 21.6) DALYs. This translated to modest cost
      offsets of AUD27 311 (-$1803; $58 242) and a net cost per DALY saved of AUD29 798
      (dominated; $0.26M). CONCLUSIONS: BAEW was affordable and cost-effective, and
      generated substantial spin-offs in terms of activity beyond funding levels.
      Elements fundamental to its success and any potential cost efficiencies
      associated with scaling-up now require identification.

PMID- 23554383
TI  - Fabrication of nature-inspired microfluidic network for perfusable tissue
      constructs.
AB  - A microreplication method is presented to transfer nature optimized vascular
      network of leaf venation into various synthetic matrixes. The biomaterial
      hydrogel with these microfluidic networks is proven to facilitate the growth of
      endothelial cells and simultaneously function as convection pathways to transport
      nutrients and oxygen in a pump-free bioreactor setup, which is crucial for the
      long-term viability of encapsulated cells. 

PMID- 23554384
TI  - Improving of red colorants production by a new Penicillium purpurogenum strain in
      submerged culture and the effect of different parameters in their stability.
AB  - There is a worldwide interest in the development of processes for colorants
      production from natural sources such as microorganism. The aim of this study was
      to optimize red colorants production by Penicillium purpurogenum DPUA 1275 and to
      evaluate the effect of pH, temperature, salts and polymers on the stability of
      these colorants. Under optimized conditions, a 78% increase in red colorants
      production was achieved. The best pH and temperature conditions were obtained at
      pH 8.0 and 70 degrees C, respectively. In the presence of salts NaCl and Na2 SO4
      , both at concentrations of 0.1 and 0.5 M in Mcllvaine buffer (pH 8.0), the red
      colorants showed good stability. In the presence of both polymers polyethylene
      glycol and sodium polyacrylate, the red colorants kept their color intensity.
      Thus, this study presents characteristics of red colorants produced by P.
      purpurogenum that can be applied in different industries after toxicological
      examination.

PMID- 23554385
TI  - Socioeconomic status, infant feeding practices and early childhood obesity.
AB  - BACKGROUND: Children from low socioeconomic households are at greater risk of
      obesity. As breastfeeding can protect against child obesity, disadvantaged
      infants are less likely to breastfeed relative to more advantaged children.
      Whether infant feeding patterns, as well as other maternal characteristics
      mediate the association between social class and obesity has not been established
      in available research. OBJECTIVES: Examine the impact of infant feeding practices
      on child obesity and identify the mechanisms that link socioeconomic status (SES)
      with child obesity. METHODS: Based on a nationally representative longitudinal
      survey (ECLS-B) of early childhood (n = 8030), we examine how breastfeeding
      practices, the early introduction of solid foods and putting an infant to bed
      with a bottle mediate the relationship between social class and early childhood
      obesity relative to the mediating influence of other maternal characteristics
      (BMI, age at birth, smoking, depression and daycare use). RESULTS: Infants
      predominantly fed formula for the first 6 months were about 2.5 times more likely
      to be obese at 24 months of age relative to infants predominantly fed breast
      milk. The early introduction of solid foods (< 4 months) and putting the child to
      bed with a bottle also increased the likelihood of obesity. Unhealthy infant
      feeding practices were the primary mechanism mediating the relationship between
      SES and early childhood obesity. Results are consistent across measures of child
      obesity although the effect size of infant feeding practices varies. CONCLUSIONS:
      The encouragement and support of breastfeeding and other healthy feeding
      practices are especially important for low socioeconomic children who are at
      increased risk of early childhood obesity. Targeting socioeconomically
      disadvantaged mothers for breastfeeding support and for infant-led feeding
      strategies may reduce the negative association between SES and child obesity. The
      implications are discussed in terms of policy and practice.

PMID- 23554386
TI  - Conspecific brood parasitism in the white-faced ibis Plegadis chihi (Aves:
      Pelecaniformes) revealed by microsatellites' based kinship-reconstruction.
AB  - The white-faced ibis Plegadis chihi Vieillot, 1817 (Pelecaniformes:
      Threskiornithidae) is a socially monogamous colonially breeding bird in which
      behavioral and ecological observations suggest the occurrence of conspecific
      brood parasitism (CBP). We inferred aspects of the genetic mating system of P.
      chihi in nature, using a genetic approach in the absence of parental information.
      We used five heterologous microsatellite loci and a multiple-step methodological
      approach to infer kinship patterns among 104 pairs of nestlings sampled inside 80
      nests in a breeding colony from southern Brazil. The estimated effective
      population size was 69 white-faced ibises (95% CI: 50-98), enough to ensure long
      term population survival. Kinship patterns were identified for 38% of the
      analyzed pairs: 60% of the diagnosed pairs were identified as full-siblings, 2.5%
      as half-siblings and 37.5% as unrelated individuals. CBP could explain the
      presence of unrelated nestlings within broods, in agreement with available non
      genetic evidence. The presence of half-siblings within broods could indicate
      extra-pair paternity. Results suggest that a non-strictly monogamous genetic
      mating system may be present in the white-faced ibis. This study is the first
      molecular approach to better characterize the reproductive behavior of P. chihi
      in the wild. Our findings set the stage for further research to investigate the
      possible causes and consequences of alternative reproductive strategies in this
      species.

PMID- 23554387
TI  - Targeting hepatic cancer cells with pegylated dendrimers displaying N
      acetylgalactosamine and SP94 peptide ligands.
AB  - Poly(amidoamine) (PAMAM) dendrimers are branched water-soluble polymers defined
      by consecutive generation numbers (Gn) indicating a parallel increase in size,
      molecular weight, and number of surface groups available for conjugation of
      bioactive agents. In this article, we compare the biodistribution of N
      acetylgalactosamine (NAcGal)-targeted [(14) C]1 -G5-(NH2 )5 -(Ac)108 -(NAcGal)14
      particles to non-targeted [(14) C]1 -G5-(NH2 )127 and PEGylated [(14) C]1 -G5
      (NH2 )44 -(Ac)73 -(PEG)10 particles in a mouse hepatic cancer model. Results show
      that both NAcGal-targeted and non-targeted particles are rapidly cleared from the
      systemic circulation with high distribution to the liver. However, NAcGal
      targeted particles exhibited 2.5-fold higher accumulation in tumor tissue
      compared to non-targeted ones. In comparison, PEGylated particles showed a 16
      fold increase in plasma residence time and a 5-fold reduction in liver
      accumulation. These results motivated us to engineer new PEGylated G5 particles
      with PEG chains anchored to the G5 surface via acid-labile cis-aconityl linkages
      where the free PEG tips are functionalized with NAcGal or SP94 peptide to
      investigate their potential as targeting ligands for hepatic cancer cells as a
      function of sugar conformation (alpha versus beta), ligand concentration (100
      4000 nM), and incubation time (2 and 24 hours) compared to fluorescently (Fl)
      labeled and non-targeted G5-(Fl)6 -(NH2 )122 and G5-(Fl)6 -(Ac)107 -(cPEG)15
      particles. Results show G5-(Fl)6 -(Ac)107 -(cPEG[NAcGalbeta ])14 particles
      achieve faster uptake and higher intracellular concentrations in HepG2 cancer
      cells compared to other G5 particles while escaping the non-specific adsorption
      of serum protein and phagocytosis by Kupffer cells, which make these particles
      the ideal carrier for selective drug delivery into hepatic cancer cells. 

PMID- 23554388
TI  - Acute hospital admissions from nursing homes: predictors of unwarranted
      variation?
AB  - BACKGROUND: The geriatric nursing home population is frail and vulnerable to
      sudden changes in their health condition. Very often, these incidents lead to
      hospitalization, in which many cases represent an unfavourable discontinuity of
      care. Analysis of variation in hospitalization rates among nursing homes where
      similar rates are expected may identify factors associated with unwarranted
      variation. OBJECTIVES: To 1) quantify the overall and diagnosis specific
      variation in hospitalization rates among nursing homes in a well-defined area
      over a two-year period, and 2) estimate the associations between the
      hospitalization rates and characteristics of the nursing homes. METHOD: The acute
      hospital admissions from 38 nursing homes to two hospitals were identified
      through ambulance records and linked to hospital patient journals (n = 2451).
      Overall variation in hospitalization rates for 2 consecutive years was tested
      using chi-square and diagnosis-specific variation using Systematic Component of
      Variation. Associations between rates and nursing home characteristics were
      tested using multiple regression and ANOVA. RESULTS: Annual hospitalization rates
      varied significantly between 0.16 and 1.49 per nursing home. Diagnoses at
      discharge varied significantly between the nursing homes. The annual
      hospitalization rates correlated significantly with size (r = -0.38) and
      percentage short-term beds (r = 0.41), explaining 32% of the variation observed
      (R (2) = 0.319). No association was found for ownership status (r = 0.05) or
      location of the nursing home (p = 0.52). CONCLUSION: A more than nine-fold
      variation in annual hospitalization rates among the nursing homes in one
      municipality suggests the presence of unwarranted variation. This finding demands
      for political action to improve the premises for a more uniform practice in
      nursing homes.

PMID- 23554389
TI  - Differences in social relations between persons with type 2 diabetes and the
      general population.
AB  - AIMS: Poor social support and lack of social network are well-established risk
      factors for morbidity and mortality in general populations. Good social
      relations, such as social support and network contacts, are associated with
      better self-management and fewer psychosocial problems in persons with type 2
      diabetes. The aim of this study was to investigate whether persons with type 2
      diabetes have poorer social relations than the general population. METHODS: We
      conducted a cross-sectional survey in three settings: a specialist diabetes
      clinic (SDC) (n = 1084), a web panel (WP) consisting of persons with type 2
      diabetes (n = 1491) and a sample from the 2010 Danish Health and Morbidity
      Survey, representative of the general population (n = 15,165). We compared social
      relations using multivariate logistic regression. RESULTS: Compared to the
      general population, persons with type 2 diabetes more often lived without a
      partner (SDC, OR 1.75, 95% CI 1.49-2.06; WP, OR 1.64, 95% CI 1.43-1.87), met with
      family less than once a month (SDC, OR 1.78, 95% CI 1.40-2.27; WP, OR 2.35, 95%
      CI 1.94-2.84) and were less certain they could count on help from others in case
      of illness (WP, OR 1.23, 95% CI 1.08-1.41). CONCLUSIONS: Our findings suggest
      that persons with type 2 diabetes have poorer social relations than the general
      population. From a public health point of view, special attention is needed with
      regards to strengthening existing networks and establishing alternative networks
      among persons with type 2 diabetes.

PMID- 23554390
TI  - Prevention of falls in the elderly: a review.
AB  - AIMS: Falls often result in soft tissue injuries, dislocations, fractures,
      longstanding pain and reduced quality of life. Therefore, fall preventive
      programmes have been developed. METHODS: In this review, we evaluate programmes
      that in randomized controlled trials (RCT) have been shown with fall reducing
      effect. RESULTS: Physical exercise that includes several training modalities,
      especially balance and strength training, is the only intervention programme that
      reduces both the number of fallers and the number of falls in community dwellers.
      Home hazards modification reduces the fall risk in community-living elderly but
      has the best effects in high risk groups when the programme is led by
      occupational therapists. Vitamin D supplement in those with low levels of vitamin
      D, adjustment of psychotropic medication and modification of multi-pharmacy are
      drug-related programmes that reduce the fall risk. Anti-slip shoe devices in
      elderly who walk outdoors during icy conditions and multifaceted podiatry to
      patients with specific foot disability are interventions targeted at the lower
      extremities with a fall-reducing effect. First eye cataract surgery and
      pacemakers in patients with cardio-inhibitory carotid sinus hypersensitivity are
      surgical procedures with fall-reducing effect. Multifactorial standardized
      preventive programmes that include an exercise component and individually
      designed subject-specific programmes also reduce the number of falls.
      CONCLUSIONS: Fall preventive interventions should be provided to elderly by a
      structured approach, especially to high risk groups, as to reduce the number of
      falls and fallers.

PMID- 23554391
TI  - Experimental and theoretical investigation of multistage extraction of 1,3
      propanediol using the extraction system phosphate/1-butyl-3-methylimidazolium
      trifluoromethanesulfonate/water.
AB  - The separation of 1,3-propanediol from fermentation broth is a challenging and
      energy-demanding step using conventional unit operations. One alternative process
      is the use of an aqueous two-phase system incorporating ionic liquids to use
      synergy effects of both technologies. Within this manuscript, the technical
      feasibility of the extraction of 1,3-propanediol using the aqueous two-phase
      system phosphate (salt)/1-butyl-3-methylimidazolium trifluoromethanesulfonate
      (ionic liquid)/water in a continuously operated process in pilot-scale is
      presented. The extraction was performed in a multistage mixer-settler unit and
      successfully modeled with an equilibrium-stage model and correlations to describe
      the liquid-liquid equilibrium of the salt/ionic liquid/water two-phase system.
      The developed and validated model was used for a further investigation of the
      influence of different process parameters in the determined operating window.
      Theses parameters include the number of stages, the phase ratio, the pH, and the
      mass fraction of the involved components. The results prove that the phosphate
      and 1-butyl-3-methylimidazolium trifluoromethanesulfonate mass fraction, the
      phase ratio, and the number of stages have a considerable influence on the
      recovery of 1,3-propanediol, whereas the pH value has only a smaller impact.
      Those results can be used for optimization of the system as well as for targeting
      future research within this area.

PMID- 23554392
TI  - Photosynthetic circadian rhythmicity patterns of Symbiodinium, [corrected] the
      coral endosymbiotic algae.
AB  - Biological clocks are self-sustained endogenous timers that enable organisms
      (from cyanobacteria to humans) to anticipate daily environmental rhythms, and
      adjust their physiology and behaviour accordingly. Symbiotic corals play a
      central role in the creation of biologically rich ecosystems based on mutualistic
      symbioses between the invertebrate coral and dinoflagellate protists from the
      genus Symbiodinium. In this study, we experimentally establish that Symbiodinium
      photosynthesis, both as a free-living unicellular algae and as part of the
      symbiotic association with the coral Stylophora pistillata, is 'wired' to the
      circadian clock mechanism with a 'free-run' cycle close to 24 h. Associated
      photosynthetic pigments also showed rhythmicity under light/dark conditions and
      under constant light conditions, while the expression of the oxygen-evolving
      enhancer 1 gene (within photosystem II) coincided with photosynthetically evolved
      oxygen in Symbiodinium cultures. Thus, circadian regulation of the Symbiodinium
      photosynthesis is, however, complicated as being linked to the coral/host that
      have probably profound physiochemical influence on the intracellular environment.
      The temporal patterns of photosynthesis demonstrated here highlight the
      physiological complexity and interdependence of the algae circadian clock
      associated in this symbiosis and the plasticity of algae regulatory mechanisms
      downstream of the circadian clock.

PMID- 23554393
TI  - Human melanopsin forms a pigment maximally sensitive to blue light (lambdamax ~
      479 nm) supporting activation of G(q/11) and G(i/o) signalling cascades.
AB  - A subset of mammalian retinal ganglion cells expresses an opsin photopigment
      (melanopsin, Opn4) and is intrinsically photosensitive. The human retina contains
      melanopsin, but the literature lacks a direct investigation of its spectral
      sensitivity or G-protein selectivity. Here, we address this deficit by studying
      physiological responses driven by human melanopsin under heterologous expression
      in HEK293 cells. Luminescent reporters for common second messenger systems
      revealed that light induces a high amplitude increase in intracellular calcium
      and a modest reduction in cAMP in cells expressing human melanopsin, implying
      that this pigment is able to drive responses via both Gq and Gi/o class G
      proteins. Melanopsins from mouse and amphioxus had a similar profile of G-protein
      coupling in HEK293 cells, but chicken Opn4m and Opn4x pigments exhibited some Gs
      activity in addition to a strong Gq/11 response. An action spectrum for the
      calcium response in cells expressing human melanopsin had the predicted form for
      an opsin : vitamin A1 pigment and peaked at 479 nm. The G-protein selectivity and
      spectral sensitivity of human melanopsin is similar to that previously described
      for rodents, supporting the utility of such laboratory animals for developing
      methods of manipulating this system using light or pharmacological agents.

PMID- 23554395
TI  - Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia
      infection in a wild rodent population.
AB  - The discovery of the key role of Toll-like receptors (TLRs) in initiating innate
      immune responses and modulating adaptive immunity has revolutionized our
      understanding of vertebrate defence against pathogens. Yet, despite their central
      role in pathogen recognition and defence initiation, there is little information
      on how variation in TLRs influences disease susceptibility in natural
      populations. Here, we assessed the extent of naturally occurring polymorphisms at
      TLR2 in wild bank voles (Myodes glareolus) and tested for associations between
      TLR2 variants and infection with Borrelia afzelii, a common tick-transmitted
      pathogen in rodents and one of the causative agents of human Lyme disease. Bank
      voles in our population had 15 different TLR2 haplotypes (10 different haplotypes
      at the amino acid level), which grouped in three well-separated clusters. In a
      large-scale capture-mark-recapture study, we show that voles carrying TLR2
      haplotypes of one particular cluster (TLR2c2) were almost three times less likely
      to be Borrelia infected than animals carrying other haplotypes. Moreover,
      neutrality tests suggested that TLR2 has been under positive selection. This is,
      to our knowledge, the first demonstration of an association between TLR
      polymorphism and parasitism in wildlife, and a striking example that genetic
      variation at innate immune receptors can have a large impact on host resistance.

PMID- 23554394
TI  - The spatio-temporal colonization and diversification across the Indo-Pacific by a
      'great speciator' (Aves, Erythropitta erythrogaster).
AB  - The Indo-Pacific region has arguably been the most important area for the
      formulation of theories about biogeography and speciation, but modern studies of
      the tempo, mode and magnitude of diversification across this region are scarce.
      We study the biogeographic history and characterize levels of diversification in
      the wide-ranging passerine bird Erythropitta erythrogaster using molecular,
      phylogeographic and population genetics methods, as well as morphometric and
      plumage analyses. Our results suggest that E. erythrogaster colonized the Indo
      Pacific during the Pleistocene in an eastward direction following a stepping
      stone pathway, and that sea-level fluctuations during the Pleistocene may have
      promoted gene flow only locally. A molecular species delimitation test suggests
      that several allopatric island populations of E. erythrogaster may be regarded as
      species. Most of these putative new species are further characterized by
      diagnostic differences in plumage. Our study reconfirms the E. erythrogaster
      complex as a 'great speciator': it represents a complex of up to 17
      allopatrically distributed, reciprocally monophyletic and/or morphologically
      diagnosable species that originated during the Pleistocene. Our results support
      the view that observed latitudinal gradients of genetic divergence among avian
      sister species may have been affected by incomplete knowledge of taxonomic limits
      in tropical bird species.

PMID- 23554397
TI  - Trends in intakes and sources of solid fats and added sugars among U.S. children
      and adolescents: 1994-2010.
AB  - BACKGROUND: There are increasing global concerns about improving the dietary
      intakes of children and adolescents. In the United States (U.S.), the focus is on
      reducing energy from foods and beverages that provide empty calories from solid
      fats and added sugars (SoFAS). OBJECTIVE: We examine trends in intakes and
      sources of solid fat and added sugars among U.S. 2-18 year olds from 1994 to
      2010. METHODS: Data from five nationally representative surveys, the Continuing
      Survey of Food Intakes by Individuals Surveys (1994-1996) and the What We Eat In
      America, National Health and Nutrition Examination Surveys (2003-2004, 2005-2006,
      2007-2008 and 2009-2010) were used to examine key food sources and energy from
      solid fats and added sugars. Sample sizes ranged from 2594 to 8259 per survey
      period, for a total of 17 268 observations across the five surveys. Food files
      were linked over time to create comparable food groups and nutrient values.
      Differences were examined by age, race/ethnicity and family income. RESULTS:
      Daily intake of energy from SoFAS among U.S. 2-18 year olds decreased from 1994
      to 2010, with declines primarily detected in the recent time periods. Solid fats
      accounted for a greater proportion of total energy intake than did added sugars.
      CONCLUSIONS: Although the consumption of solid fats and added sugars among
      children and adolescents in the U.S. decreased between 1994-1998 and 2009-2010,
      mean intakes continue to exceed recommended limits.

PMID- 23554398
TI  - Assembled microcapsules by doxorubicin and polysaccharide as high effective
      anticancer drug carriers.
AB  - Doxorubicin, together with the modified polysaccharide (alginate dialdehyde), was
      used as a wall material to fabricate microcapsules through self-cross-linking by
      a template method. The microcapsules as-prepared are pH-responsive. Relevant
      scanning electronic microscopy, atom force microscopy and confocal laser scanning
      microscopy confirm the morphology of the uniform microcapsules. The spectroscopic
      results show that the microcapsules are assembled through electrostatic
      interaction and Schiff's base covalent bonding. Doxorubicin can be released
      sustainably from the capsules in buffer solution at a lower pH value. The
      cellular uptake of the microcapsules and drug release induced by acidic
      microenvironment are time-dependent processes. The cell cytotoxicity experiments
      in vitro demonstrate that the doxorubicin-based microcapsules have high
      efficiency to kill the cancer cells. 

PMID- 23554396
TI  - Ancient host shifts followed by host conservatism in a group of ant parasitoids.
AB  - While ant colonies serve as host to a diverse array of myrmecophiles, few
      parasitoids are able to exploit this vast resource. A notable exception is the
      wasp family Eucharitidae, which is the only family of insects known to
      exclusively parasitize ants. Worldwide, approximately 700 Eucharitidae species
      attack five subfamilies across the ant phylogeny. Our goal is to uncover the
      pattern of eucharitid diversification, including timing of key evolutionary
      events, biogeographic patterns and potential cophylogeny with ant hosts. We
      present the most comprehensive molecular phylogeny of Eucharitidae to date,
      including 44 of the 53 genera and fossil-calibrated estimates of divergence
      dates. Eucharitidae arose approximately 50 Ma after their hosts, during the time
      when the major ant lineages were already established and diversifying. We
      incorporate host association data to test for congruence between eucharitid and
      ant phylogenies and find that their evolutionary histories are more similar than
      expected at random. After a series of initial host shifts, clades within
      Eucharitidae maintained their host affinity. Even after multiple dispersal events
      to the New World and extensive speciation within biogeographic regions,
      eucharitids remain parasitic on the same ant subfamilies as their Old World
      relatives, suggesting host conservatism despite access to a diverse novel ant
      fauna.

PMID- 23554399
TI  - Computational fluid modeling and performance analysis of a bidirectional rotating
      perfusion culture system.
AB  - A myriad of bioreactor configurations have been investigated as extracorporeal
      medical support systems for temporary replacement of vital organ functions. In
      recent years, studies have demonstrated that the rotating bioreactors have the
      potential to be utilized as bioartificial liver assist devices (BLADs) owing to
      their advantage of ease of scalability of cell-culture volume. However, the fluid
      movement in the rotating chamber will expose the suspended cells to unwanted flow
      structures with abnormally high shear conditions that may result in poor cell
      stability and in turn lower the efficacy of the bioreactor system. In this study,
      we compared the hydrodynamic performance of our modified rotating bioreactor
      design with that of an existing rotating bioreactor design. Computational fluid
      dynamic analysis coupled with experimental results were employed in the
      optimization process for the development of the modified bioreactor design. Our
      simulation results showed that the modified bioreactor had lower fluid induced
      shear stresses and more uniform flow conditions within its rotating chamber than
      the conventional design. Experimental results revealed that the cells within the
      modified bioreactor also exhibited better cell-carrier attachment, higher
      metabolic activity, and cell viability compared to those in the conventional
      design. In conclusion, this study was able to provide important insights into the
      flow physics within the rotating bioreactors, and help enhanced the hydrodynamic
      performance of an existing rotating bioreactor for BLAD applications.

PMID- 23554400
TI  - Confocal Raman imaging study showing macrophage mediated biodegradation of
      graphene in vivo.
AB  - This study is focused on the crucial issue of biodegradability of graphene under
      in vivo conditions. Characteristic Raman signatures of graphene are used to three
      dimensionally (3D) image its localization in lung, liver, kidney and spleen of
      mouse and identified gradual development of structural disorder, happening over a
      period of 3 months, as indicated by the formation of defect-related D'band, line
      broadening of D and G bands, increase in ID /IG ratio and overall intensity
      reduction. Prior to injection, the carboxyl functionalized graphene of lateral
      size ~200 nm is well dispersed in aqueous medium, but 24 hours post injection,
      larger aggregates of size up to 10 MUm are detected in various organs. Using
      Raman cluster imaging method, temporal development of disorder is detected from
      day 8 onwards, which begins from the edges and grows inwards over a period of 3
      months. The biodegradation is found prominent in graphene phagocytosed by tissue
      bound macrophages and the gene expression studies of pro-inflammatory cytokines
      indicated the possibility of phagocytic immune response. In addition, in vitro
      studies conducted on macrophage cell lines also show development of structural
      disorder in the engulfed graphene, reiterating the role of macrophages in
      biodegradation. This is the first report providing clear evidence of in vivo
      biodegradation of graphene and these results may radically change the perspective
      on potential biomedical applications of graphene. 

PMID- 23554401
TI  - Ethnic variations in overweight and obesity among children over time: findings
      from analyses of the Health Surveys for England 1998-2009.
AB  - BACKGROUND: The increase in the prevalence of obesity among children and
      adolescents in England since the mid-1990s has been dramatic. Cross-sectional
      evidence suggests ethnic variations in childhood obesity prevalence. OBJECTIVES:
      The objective of the study was to examine whether and how ethnic variations in
      childhood overweight/obesity have changed over time, and are affected by
      socioeconomic factors. METHOD: This study uses logistic regression to analyse
      ethnic differences in the relative likelihood of being at or above the age- and
      gender-specific thresholds for overweight and obesity developed by the
      International Obesity Task Force among children aged between 2 and 15 from 11
      ethnic groups included in the Health Surveys for England between 1998 and 2009,
      adjusting for age, gender, year of data collection and equivalized household
      income. We separately analyse the likelihood of being at or above the thresholds
      for overweight (but below those for obesity) and obesity. RESULTS: Trends in
      overweight/obesity over time among ethnic minority groups do not follow those of
      white English children. Black African children had higher rates of overweight and
      obesity, which appear to have peaked, and black Caribbean children had higher
      rates of obesity than other groups examined, which appear to continue rising.
      These differences were not explained by socioeconomic variations between groups.
      CONCLUSION: Policies are required that encourage healthy lifestyles among ethnic
      minority young people, while engaging with the complexities associated with these
      choices during childhood and adolescence.

PMID- 23554403
TI  - Increased serum IgG and IgA in overweight children relate to a less favourable
      metabolic phenotype.
AB  - BACKGROUND: The adaptive immune system has emerged as an unexpected modulator of
      insulin resistance. B lymphocytes accumulate in adipose tissue and produce
      pathogenic antibodies that cause insulin resistance. OBJECTIVE: We studied
      whether circulating immunoglobulins (IgG, IgA and IgM) were related to metabolic
      risk markers in pre-pubertal children with and without overweight. DESIGN AND
      METHODS: Subjects were 270 asymptomatic pre-pubertal Caucasian children (145
      lean, 125 overweight) recruited in a primary care setting. Assessments included
      serum IgG, IgA and IgM concentrations (nephelometry), insulin resistance (HOMA
      IR) and fasting lipids (triacylglycerol and high-density lipoprotein [HDL]
      cholesterol). RESULTS: Overweight children had higher IgG and IgA serum levels
      than lean children (P <= 0.01). Increasing serum IgG and IgA, but not IgM, were
      associated with a less favourable metabolic phenotype, consisting of higher HOMA
      IR and triacylglycerol and lower HDL-cholesterol, particularly in obese children,
      in whom serum IgG and IgA were both independently associated with HOMA-IR (beta =
      0.308, P = 0.017, r2  = 9.5% and beta = 0.361, P = 0.005, r2  = 13.0%,
      respectively) and triacylglycerol (beta = 0.343, P = 0.006, r2  = 11.1% and beta
      = 0.354, P = 0.003, r2  = 12.2%, respectively). CONCLUSIONS: Increased
      circulating IgG and IgA in overweight children are associated with a less
      favourable metabolic phenotype, particularly in obese children. These results
      suggest a relationship between adaptive immunity and insulin resistance in
      childhood obesity.

PMID- 23554402
TI  - The potential of tissue engineering for developing alternatives to animal
      experiments: a systematic review.
AB  - An underexposed ethical issue raised by tissue engineering is the use of
      laboratory animals in tissue engineering research. Even though this research
      results in suffering and loss of life in animals, tissue engineering also has
      great potential for the development of alternatives to animal experiments. With
      the objective of promoting a joint effort of tissue engineers and alternative
      experts to fully realise this potential, this study provides the first
      comprehensive overview of the possibilities of using tissue-engineered constructs
      as a replacement of laboratory animals. Through searches in two large biomedical
      databases (PubMed, Embase) and several specialised 3R databases, 244 relevant
      primary scientific articles, published between 1991 and 2011, were identified. By
      far most articles reviewed related to the use of tissue-engineered skin/epidermis
      for toxicological applications such as testing for skin irritation. This review
      article demonstrates, however, that the potential for the development of
      alternatives also extends to other tissues such as other epithelia and the liver,
      as well as to other fields of application such as drug screening and basic
      physiology. This review discusses which impediments need to be overcome to
      maximise the contributions that the field of tissue engineering can make, through
      the development of alternative methods, to the reduction of the use and suffering
      of laboratory animals.

PMID- 23554404
TI  - Effect of enzyme dehydration on alcalase-catalyzed dipeptide synthesis in near
      anhydrous organic media.
AB  - The effect of enzyme dehydration by molecular sieves on the coupling of
      phenylalanine amide and the carbamoylmethyl ester of N-protected phenylalanine in
      near-anhydrous tetrahydrofuran was investigated. This coupling was catalyzed by
      Alcalase covalently immobilized onto macroporous acrylic beads (Cov); these
      immobilized enzymes were hydrated prior to use. The dehydration kinetics of Cov
      by molecular sieve powder were determined by incubating Cov with different
      amounts of molecular sieve powder for different periods of time (0-80 h).
      Subsequently, the remaining coupling activity of Cov was measured. Dehydration
      induced inactivation of Cov by molecular sieve powder was found to occur in three
      phases: (1) an initial, rapid, major dehydration-induced inactivation that takes
      place during the first activity measurement, (2) a phase of first-order
      inactivation, and (3) a plateau phase in activity. These dehydration kinetics
      were incorporated into a previously found reaction kinetics model. The resulting
      model was then used to fit progress curve data of the coupling in the presence of
      different amounts of molecular sieve powder. Upon establishment of parameter
      values, the model was used to predict independent data sets and found to work
      well.

PMID- 23554405
TI  - Micro-/nanometer rough structure of a superhydrophobic biodegradable coating by
      electrospraying for initial anti-bioadhesion.
AB  - A novel superhydrophobic biodegradable coating with micro-/nanometer rough
      structure, fabricated by co-electrospraying poly(L-lactide) (PLLA) and modified
      silica nanoparticles (MSNs), exhibits good anti-adhesion behavior towards
      bacteria and cells in the initial culturing phase, which makes it a promising
      technology for preparing medical device coatings. 

PMID- 23554406
TI  - The development and implantation of a biologically derived allograft scaffold.
AB  - Biologically derived scaffolds are becoming viable treatment options for
      tissue/organ repair and regeneration. A continuing hurdle is the need for a
      functional blood supply to and from the implanted scaffold. We have addressed
      this problem by constructing an acellular ileal scaffold with an attached
      vascular network suitable for implantation and immediate reperfusion with the
      host's blood. Using a vascular perfusion approach, a segment of porcine ileum up
      to 30 cm long, together with its attached vasculature, was decellularized as a
      single entity. The quality of the decellularized scaffold was assessed
      histologically and using molecular tools. To establish vascular perfusion
      potentials of the scaffold, a right-sided nephrectomy and end-to-end anastomosis
      of the decellularized scaffold's vasculature to a renal artery and vein were
      performed in a pig of similar size to the donor animal. Lengths of ileal
      scaffold, together with its attached vasculature, were successfully
      decellularized, with no evidence of intact cells/nuclear material or collagen
      degradation. The scaffold's decellularized vascular network demonstrated optimum
      perfusion at 1, 2 and 24 h post-implantation and the mesenteric arcade remained
      patent throughout the assessment. The 1, 2 and 24 h explanted scaffolds
      demonstrated signs of cellular attachment, with cells positive for CD68 and CD133
      on the vascular luminal aspect. It is possible to decellularize clinically
      relevant lengths of small intestine, together with the associated vasculature, as
      a single segment. The functional vascular network may represent a route for
      recellularization for future regeneration of bowel tissue for patients with short
      bowel syndrome.

PMID- 23554408
TI  - Promotion of muscle regeneration by myoblast transplantation combined with the
      controlled and sustained release of bFGFcpr.
AB  - Although myoblast transplantation is an attractive method for muscle
      regeneration, its efficiency remains limited. The efficacy of myoblast
      transplantation in combination with the controlled and sustained delivery of
      basic fibroblast growth factor (bFGF) was investigated. Defects of thigh muscle
      in Sprague-Dawley (SD) rats were created, and GFP-positive myoblasts were
      subsequently transplanted. The rats were divided into three groups. In control
      group 1 (C1) only myoblasts were transplanted, while in control group 2 (C2)
      myoblasts were introduced along with empty gelatin hydrogel microspheres. In the
      experimental group (Ex), myoblasts were transplanted along with bFGF incorporated
      into gelatin hydrogel microspheres. Four weeks after transplantation, GFP
      positive myoblasts were found to be integrated into the recipient muscle and to
      contribute to muscle fibre regeneration in all groups. A significantly higher
      expression level of GFP in the Ex group demonstrated that the survival rate of
      transplanted myoblasts in Ex was remarkably improved compared with that in C1 and
      C2. Furthermore, myofibre regeneration, characterized by centralization of the
      nuclei, was markedly accelerated in Ex. The expression level of CD31 in Ex was
      higher than that in both C1 and C2, but the differences were not statistically
      significant. A significantly higher expression level of Myogenin and a lower
      expression level of MyoD1 were both observed in Ex after 4 weeks, suggesting the
      promotion of differentiation to myotubes. Our findings suggest that the
      controlled and sustained release of bFGF from gelatin hydrogel microspheres
      improves the survival rate of transplanted myoblasts and promotes muscle
      regeneration by facilitating myogenesis rather than angiogenesis.

PMID- 23554409
TI  - Interaction between abscisic acid and nitric oxide in PB90-induced catharanthine
      biosynthesis of catharanthus roseus cell suspension cultures.
AB  - Elicitations are considered to be an important strategy to improve production of
      secondary metabolites of plant cell cultures. However, mechanisms responsible for
      the elicitor-induced production of secondary metabolites of plant cells have not
      yet been fully elucidated. Here, we report that treatment of Catharanthus roseus
      cell suspension cultures with PB90, a protein elicitor from Phytophthora
      boehmeriae, induced rapid increases of abscisic acid (ABA) and nitric oxide (NO),
      subsequently followed by the enhancement of catharanthine production and up
      regulation of Str and Tdc, two important genes in catharanthine biosynthesis.
      PB90-induced catharanthine production and the gene expression were suppressed by
      the ABA inhibitor and NO scavenger respectively, showing that ABA and NO are
      essential for the elicitor-induced catharanthine biosynthesis. The relationship
      between ABA and NO in mediating catharanthine biosynthesis was further
      investigated. Treatment of the cells with ABA triggered NO accumulation and
      induced catharanthine production and up-regulation of Str and Tdc. ABA-induced
      catharanthine production and gene expressions were suppressed by the NO
      scavenger. Conversely, exogenous application of NO did not stimulate ABA
      generation and treatment with ABA inhibitor did not suppress NO-induced
      catharanthine production and gene expressions. Together, the results showed that
      both NO and ABA were involved in PB90-induced catharanthine biosynthesis of C.
      roseus cells. Furthermore, our data demonstrated that ABA acted upstream of NO in
      the signaling cascade leading to PB90-induced catharanthine biosynthesis of C.
      roseus cells.

PMID- 23554410
TI  - Kba.62 and S100 protein expression in cytologic samples of metastatic malignant
      melanoma.
AB  - The diagnosis of melanoma can be challenging, especially in metastatic lesions,
      due to the ability of melanoma cells to morphologically mimic carcinoma, sarcoma
      and even lymphoma cells. Moreover, melanomas can exhibit negative immunostaining
      for the melanoma markers HMB-45 and MART-1/Melan-A, often used in the diagnosis
      of this tumor. KBA.62 is a recently described antibody that reacts with benign
      and malignant melanocytic proliferations. In this study, we report our experience
      with KBA.62 and S100 protein immunostaining in the diagnosis of metastatic
      melanoma on fine-needle aspiration and effusion samples. We reviewed 60 cytology
      samples from 58 patients with metastatic melanoma. Our results showed that KBA.62
      stained 75% of the cases and S100 protein 87% of the cases. KBA.62 and S100
      protein stained the majority of metastatic melanomas that were negative for HMB
      45 and MART-1; KBA.62 stained 73% of the cases and S100 protein 73% of the cases.
      The majority (85%) of the cases negative for HMB-45 and MART-1 were positive for
      KBA.62 and/or S100 protein. Additionally, we also observed that KBA.62 staining
      was positive in the majority of epithelioid and spindle cell type melanoma cells.
      In conclusion, the performances of KBA.62 and S100 protein were similar and both
      markers are useful in the diagnosis of metastatic melanoma in cytology material,
      especially when the tumor cells lack expression of HMB-45 and MART-1.

PMID- 23554411
TI  - Agonism of Wnt-beta-catenin signalling promotes mesenchymal stem cell (MSC)
      expansion.
AB  - Promoting mesenchymal stem cell (MSC) proliferation has numerous applications in
      stem cell therapies, particularly in the area of regenerative medicine. In order
      for cell-based regenerative approaches to be realized, MSC proliferation must be
      achieved in a controlled manner without compromising stem cell differentiation
      capacities. Here we demonstrate that 6-bromoindirubin-3'-oxime (BIO) increases
      MSC beta-catenin activity 106-fold and stem cell-associated gene expression ~33
      fold, respectively, over untreated controls. Subsequently, BIO treatment
      increases MSC populations 1.8-fold in typical 2D culture conditions, as well as
      1.3-fold when encapsulated within hydrogels compared to untreated cells.
      Furthermore, we demonstrate that BIO treatment does not reduce MSC multipotency
      where MSCs maintain their ability to differentiate into osteoblasts, chondrocytes
      and adipocytes using standard conditions. Taken together, our results demonstrate
      BIO's potential utility as a proliferative agent for cell transplantation and
      tissue regeneration.

PMID- 23554412
TI  - Improvement of mammalian cell culture performance through surfactant enabled
      concentrated feed media.
AB  - The design of basal and feed media in mammalian cell culture is paramount towards
      ensuring acceptable upstream process performance in various operation modes,
      especially fed-batch culture. Mammalian cell culture media designs have evolved
      from the classical formulations designed by Eagle and Ham, to today's
      formulations designed from continuous improvement and statistical frameworks.
      Feed media is especially important for ensuring robust cell growth, productivity,
      and ensuring the product quality of recombinant therapeutics are within
      acceptable ranges. Numerous studies have highlighted the benefit of various media
      designs, supplements, and feed addition strategies towards the resulting cell
      culture process. In this work we highlight the use of a top-down level approach
      towards feed media design enabled by the use of select surfactants for the
      targeted enrichment of a chemically defined feed media. The use of the enriched
      media was able to improve product titers at g/L levels, without adversely
      impacting the growth of multiple Chinese Hamster Ovary cell lines or the product
      quality of multiple recombinant antibodies.

PMID- 23554413
TI  - Human infections and detection of Plasmodium knowlesi.
AB  - Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed
      and pig-tailed macaques. Naturally acquired human infections were thought to be
      extremely rare until a large focus of human infections was reported in 2004 in
      Sarawak, Malaysian Borneo. Human infections have since been described throughout
      Southeast Asia, and P. knowlesi is now recognized as the fifth species of
      Plasmodium causing malaria in humans. The molecular, entomological, and
      epidemiological data indicate that human infections with P. knowlesi are not
      newly emergent and that knowlesi malaria is primarily a zoonosis. Human
      infections were undiagnosed until molecular detection methods that could
      distinguish P. knowlesi from the morphologically similar human malaria parasite
      P. malariae became available. P. knowlesi infections cause a spectrum of disease
      and are potentially fatal, but if detected early enough, infections in humans are
      readily treatable. In this review on knowlesi malaria, we describe the early
      studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical
      aspects, and treatment of knowlesi malaria. We also discuss the gaps in our
      knowledge and the challenges that lie ahead in studying the epidemiology and
      pathogenesis of knowlesi malaria and in the prevention and control of this
      zoonotic infection.

PMID- 23554414
TI  - Antimicrobial resistance and virulence: a successful or deleterious association
      in the bacterial world?
AB  - Hosts and bacteria have coevolved over millions of years, during which pathogenic
      bacteria have modified their virulence mechanisms to adapt to host defense
      systems. Although the spread of pathogens has been hindered by the discovery and
      widespread use of antimicrobial agents, antimicrobial resistance has increased
      globally. The emergence of resistant bacteria has accelerated in recent years,
      mainly as a result of increased selective pressure. However, although
      antimicrobial resistance and bacterial virulence have developed on different
      timescales, they share some common characteristics. This review considers how
      bacterial virulence and fitness are affected by antibiotic resistance and also
      how the relationship between virulence and resistance is affected by different
      genetic mechanisms (e.g., coselection and compensatory mutations) and by the most
      prevalent global responses. The interplay between these factors and the
      associated biological costs depend on four main factors: the bacterial species
      involved, virulence and resistance mechanisms, the ecological niche, and the
      host. The development of new strategies involving new antimicrobials or
      nonantimicrobial compounds and of novel diagnostic methods that focus on high
      risk clones and rapid tests to detect virulence markers may help to resolve the
      increasing problem of the association between virulence and resistance, which is
      becoming more beneficial for pathogenic bacteria.

PMID- 23554417
TI  - Importance of relating efficacy measures to unbound drug concentrations for anti
      infective agents.
AB  - For the optimization of dosing regimens of anti-infective agents, it is
      imperative to have a good understanding of pharmacokinetics (PK) and
      pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to
      unbound concentrations at the site of action. For anti-infective drugs, the
      infection site is typically located outside plasma, and a drug must diffuse
      through capillary membranes to reach its target. Disease- and drug-related
      factors can contribute to differential tissue distribution. As a result, the
      assumption that the plasma concentration of drugs represents a suitable surrogate
      of tissue concentrations may lead to erroneous conclusions. Quantifying drug
      exposure in tissues represents an opportunity to relate the pharmacologically
      active concentrations to an observed pharmacodynamic parameter, such as the MIC.
      Selection of an appropriate specimen to sample and the advantages and limitations
      of the available sampling techniques require careful consideration. Ultimately,
      the goal will be to assess the appropriateness of a drug and dosing regimen for a
      specific pathogen and infection.

PMID- 23554416
TI  - Microbiology and treatment of acute apical abscesses.
AB  - Acute apical abscess is the most common form of dental abscess and is caused by
      infection of the root canal of the tooth. It is usually localized intraorally,
      but in some cases the apical abscess may spread and result in severe
      complications or even mortality. The reasons why dental root canal infections can
      become symptomatic and evolve to severe spreading and sometimes life-threatening
      abscesses remain elusive. Studies using culture and advanced molecular
      microbiology methods for microbial identification in apical abscesses have
      demonstrated a multispecies community conspicuously dominated by anaerobic
      bacteria. Species/phylotypes commonly found in these infections belong to the
      genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister,
      Streptococcus, and Treponema. Advances in DNA sequencing technologies and
      computational biology have substantially enhanced the knowledge of the microbiota
      associated with acute apical abscesses and shed some light on the etiopathogeny
      of this disease. Species richness and abundance and the resulting network of
      interactions among community members may affect the collective pathogenicity and
      contribute to the development of acute infections. Disease modifiers, including
      transient or permanent host-related factors, may also influence the development
      and severity of acute abscesses. This review focuses on the current evidence
      about the etiology and treatment of acute apical abscesses and how the process is
      influenced by host-related factors and proposes future directions in research,
      diagnosis, and therapeutic approaches to deal with this disease.

PMID- 23554415
TI  - Transmission of infection by flexible gastrointestinal endoscopy and
      bronchoscopy.
AB  - Flexible endoscopy is a widely used diagnostic and therapeutic procedure.
      Contaminated endoscopes are the medical devices frequently associated with
      outbreaks of health care-associated infections. Accurate reprocessing of flexible
      endoscopes involves cleaning and high-level disinfection followed by rinsing and
      drying before storage. Most contemporary flexible endoscopes cannot be heat
      sterilized and are designed with multiple channels, which are difficult to clean
      and disinfect. The ability of bacteria to form biofilms on the inner channel
      surfaces can contribute to failure of the decontamination process. Implementation
      of microbiological surveillance of endoscope reprocessing is appropriate to
      detect early colonization and biofilm formation in the endoscope and to prevent
      contamination and infection in patients after endoscopic procedures. This review
      presents an overview of the infections and cross-contaminations related to
      flexible gastrointestinal endoscopy and bronchoscopy and illustrates the impact
      of biofilm on endoscope reprocessing and postendoscopic infection.

PMID- 23554418
TI  - Epidemiological interpretation of studies examining the effect of antibiotic
      usage on resistance.
AB  - Bacterial resistance to antibiotics is a growing clinical problem and public
      health threat. Antibiotic use is a known risk factor for the emergence of
      antibiotic resistance, but demonstrating the causal link between antibiotic use
      and resistance is challenging. This review describes different study designs for
      assessing the association between antibiotic use and resistance and discusses
      strengths and limitations of each. Approaches to measuring antibiotic use and
      antibiotic resistance are presented. Important methodological issues such as
      confounding, establishing temporality, and control group selection are examined.

PMID- 23554422
TI  - Parainfluenza virus-3-induced cytopathic effects on lung tissue and
      bronchoalveolar lavage fluid in a bone marrow transplant recipient: a case
      report.
AB  - Parainfluenza virus type 3(PIV-3) commonly causes respiratory tract infections in
      hematopoietic stem cell transplant (HSCT) patients. The majority of PIV-3
      infections develop in patients who have undergone stem cell transplantation from
      unrelated donors. From these patients, bronchoalveolar lavage (BAL) fluid and/or
      lung biopsies are often collected and sent for evaluation of infectious
      processes. However, cytologic findings associated with a PIV-3 infection in BAL
      fluid have not been reported in the literature. We describe BAL cytology and lung
      biopsy findings in a patient who received an HSCT from a related donor and
      subsequently developed a PIV-3 infection. This patient was noted to have
      scattered reticular-nodular opacities in both lungs on computed tomogram scan and
      underwent transbronchial biopsy and BAL of the left lower lobe. Examination of
      the BAL fluid revealed scattered multinucleated giant cells intermixed with
      inflammatory cells. The lung biopsy showed organizing pneumonia associated with
      several multinucleated respiratory epithelial cells containing rare
      intracytoplasmic inclusions. Gram, periodic acid Schiff, Gomori methenamine
      silver, and acid fast stains on the biopsy specimen failed to reveal
      microorganisms. A sample of the BAL fluid sent for respiratory viral culture grew
      PIV-3. These findings suggest that the presence of giant cells in transplant
      patients with organizing pneumonia should raise suspicion of a PIV-3 infection.

PMID- 23554423
TI  - Calculating isotope concentrations using different schemes of dispersion
      parameters.
AB  - The investigated work aims to calculate the concentration of different isotopes
      through short downwind distances. A theoretical model was designed to calculate
      the isotope concentration in the wind. The mathematical calculation depends on
      wind speed, decay distance and the dilution factor to get the concentration of
      isotopes ((131)I, (133)I, (135)I and (137)Cs) detected in wind at different
      distances from a nuclear power station. There is a good agreement between the
      calculated and observed concentrations of (131)I, (133)I, (135)I and (137)Cs. 

PMID- 23554420
TI  - Insights into the origin, emergence, and current spread of a successful Russian
      clone of Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis variant Beijing B0/W148 is regarded as a successful
      clone of M. tuberculosis that is widespread in the former Soviet Union and
      respective immigrant communities. Understanding the pathobiology and
      phylogeography of this notorious strain may help to clarify its origin and
      evolutionary history and the driving forces behind its emergence and current
      dissemination. I present the first review and analysis of all available data on
      the subject. In spite of the common perception of the omnipresence of B0/W148
      across post-Soviet countries, its geographic distribution shows a peculiar clinal
      gradient. Its frequency peaks in Siberian Russia and, to a lesser extent, in the
      European part of the former Soviet Union. In contrast, the frequency of B0/W148
      is sharply decreased in the Asian part of the former Soviet Union, and it is
      absent in autochthonous populations elsewhere in the world. Placing the
      molecular, clinical, and epidemiological features in a broad historical,
      demographic, and ecological context, I put forward two interdependent hypotheses.
      First, B0/W148 likely originated in Siberia, and its primary dispersal was driven
      by a massive population outflow from Siberia to European Russia in the 1960s to
      1980s. Second, a historically recent, phylogenetically demonstrated successful
      dissemination of the Beijing B0/W148 strain was triggered by the advent and wide
      use of modern antituberculosis (anti-TB) drugs and was due to the remarkable
      capacity of this strain to acquire drug resistance. In contrast, there is some
      indication, but not yet systematic proof, of an enhanced virulence of this
      strain.

PMID- 23554424
TI  - Assessment of radiation exposure outside the radiotherapeutic room during medical
      accelerator beam emission with the use of TL detectors (radiation exposure
      outside a LINAC room).
AB  - Photon and neutron soft tissue absorbed doses near the entrance door to the
      medical LINAC treatment room were measured with the use of thermoluminescent
      detectors LiF:Mg,Cu,P in the anthropomorphic phantom. Two different therapeutic
      beams (6 and 15 MV) and four treatment techniques were involved in the present
      study. This allowed one to investigate the contribution of scattered X rays,
      secondary neutrons and gamma rays to the radiation field. Photon absorbed dose
      rates 50 cm away from the LINAC room door during emission of 15-MV X rays varied
      between 4.1*10(-4) and 5.6*10(-4) Gy h(-1), depending on the gantry position and
      the irradiation field size, whereas in the case of 6-MV therapeutic irradiation
      these doses are ~1.5 times lower. In the case of 15-MV beam emission, a mixed
      radiation field near the bunker door is observed with the photon radiation as the
      main component, which includes a 33.1 % contribution of the induced gamma
      radioactivity and ~2.1 % contribution of the neutron radiation. 

PMID- 23554425
TI  - Education and training activities on personal dosimetry service in Turkey.
AB  - A personal dosimetry service that evaluates the occupational doses for external
      and internal radiation of the radiation workers is one of the main components of
      radiation protection programme. The education and training (E&T) activities in
      this field are basic aspects of the optimisation of all exposures to radiation.
      The E&T activities in the field of occupational radiation protection at the
      national and international level are of main interest and implemented by the
      Ankara Nuclear Research and Training Center. This study describes the Turkish
      experience in E&T of the staff of dosimetry services, postgraduate students and
      medical physics experts. In Turkey, the first individual monitoring training
      course was conducted in 2012. The aim of this study is to provide a structured
      description of postgraduate courses that are addressed to qualified experts and
      medical physics experts, and the modules are mainly dedicated to individual
      monitoring. 

PMID- 23554426
TI  - Preparation of paper scintillator for detecting 3H contaminant.
AB  - Liquid scintillator (LS)-encapsulated silica was prepared by the sol-gel method
      and then was added dropwise onto a wipe paper to form a paper scintillator.
      First, the efficiencies of wipe were determined for both the paper scintillator
      and the wipe paper using a liquid scintillation counter (LSC). The efficiencies
      of wipe using the paper scintillator and the wipe paper were 88 and 36 %,
      respectively. The detection efficiencies were 5.5 % for the paper scintillator,
      46 % for the wipe paper using an LS and 0.08 % for the (3)H/(14)C survey meter,
      respectively, compared with that of a melt-on scintillator of 47 %. Second, an
      (3)H contaminant on the paper scintillator was successfully detected using a
      photomultiplier without an LSC or an (3)H/(14)C survey meter. Finally, the paper
      scintillator was able to detect beta rays of the (3)H contaminant easily without
      an LS. 

PMID- 23554427
TI  - Natural radionuclides in clay deposits: concentration and dose assessment.
AB  - Clays are among the most important industrially used minerals. Three potential
      clay mineral mining sites in Saudi Arabia were chosen, and 21 clay deposit
      samples were collected. The activity concentrations (average+/-standard
      deviation) of the naturally occurring radioactive materials (NORMs), (238)U,
      (226)Ra, (232)Th, (228)Ra and (40)K, were 49+/-20, 47+/-23, 34+/-11, 40+/-20 and
      751 Bq kg(-1), respectively. The radiation dose assessments (e.g., absorbed dose
      rate, nGy h(-1); effective dose equivalent, uSv y(-1); and effective dose rate
      due to dust inhalation, uSv y(-1)) and hazardous indices (e.g., radium equivalent
      [Ra-eq] value, external hazardous index [Hex], internal hazardous index [Hin] and
      representative gamma level [Igamma]) were calculated. The wide variations in the
      activity concentrations of the NORMs according to sampling region could be due to
      the origin of the geological formation and the geochemical behaviour of the
      NORMs. Based on calculated hazardous (external and internal) indices, there were
      no expected radiological hazardous impacts of using clay deposits as building
      materials. 

PMID- 23554428
TI  - The glucuronidation of R- and S-lorazepam: human liver microsomal kinetics, UDP
      glucuronosyltransferase enzyme selectivity, and inhibition by drugs.
AB  - The widely used hypnosedative-anxiolytic agent R,S-lorazepam is cleared
      predominantly by conjugation with glucuronic acid in humans, but the
      enantioselective glucuronidation of lorazepam has received little attention. The
      present study characterized the kinetics of the separate R and S enantiomers of
      lorazepam by human liver microsomes (HLMs) and by a panel of recombinant human
      UDP-glucuronosyltransferase (UGT) enzymes. Respective mean K(m) and V(max) values
      for R- and S-lorazepam glucuronidation by HLM were 29 +/- 8.9 and 36 +/- 10 uM,
      and 7.4 +/- 1.9 and 10 +/- 3.8 pmol/min ? mg. Microsomal intrinsic clearances
      were not significantly different, suggesting the in vivo clearances of R- and S
      lorazepam are likely to be similar. Both R- and S-lorazepam were glucuronidated
      by UGT2B4, 2B7, and 2B15, whereas R-lorazepam was additionally metabolized by the
      extrahepatic enzymes UGT1A7 and 1A10. Based on in vitro clearances and
      consideration of available in vivo and in vitro data, UGT2B15 is likely to play
      an important role in the glucuronidation of R- and S-lorazepam. However, the
      possible contribution of other enzymes and the low activities observed in vitro
      indicate that the lorazepam enantiomers are of limited use as substrate probes
      for UGT2B15. To identify potential drug-drug interactions, codeine, fluconazole,
      ketamine, ketoconazole, methadone, morphine, valproic acid, and zidovudine were
      screened as inhibitors of R- and S-lorazepam glucuronidation by HLM. In vitro-in
      vivo extrapolation suggested that, of these drugs, only ketoconazole had the
      potential to inhibit lorazepam clearance to a clinically significant extent.

PMID- 23554419
TI  - Salmonella enterica serovar Typhimurium skills to succeed in the host: virulence
      and regulation.
AB  - Salmonella enterica serovar Typhimurium is a primary enteric pathogen infecting
      both humans and animals. Infection begins with the ingestion of contaminated food
      or water so that salmonellae reach the intestinal epithelium and trigger
      gastrointestinal disease. In some patients the infection spreads upon invasion of
      the intestinal epithelium, internalization within phagocytes, and subsequent
      dissemination. In that case, antimicrobial therapy, based on fluoroquinolones and
      expanded-spectrum cephalosporins as the current drugs of choice, is indicated. To
      accomplish the pathogenic process, the Salmonella chromosome comprises several
      virulence mechanisms. The most important virulence genes are those located within
      the so-called Salmonella pathogenicity islands (SPIs). Thus far, five SPIs have
      been reported to have a major contribution to pathogenesis. Nonetheless, further
      virulence traits, such as the pSLT virulence plasmid, adhesins, flagella, and
      biofilm-related proteins, also contribute to success within the host. Several
      regulatory mechanisms which synchronize all these elements in order to guarantee
      bacterial survival have been described. These mechanisms govern the transitions
      from the different pathogenic stages and drive the pathogen to achieve maximal
      efficiency inside the host. This review focuses primarily on the virulence
      armamentarium of this pathogen and the extremely complicated regulatory network
      controlling its success.

PMID- 23554429
TI  - Levels of serum anti-Mullerian hormone, a marker for ovarian reserve, in women
      with rheumatoid arthritis.
AB  - OBJECTIVE: Fertility is reduced in women with rheumatoid arthritis (RA), even
      before diagnosis. This may be due to a diminished ovarian reserve. The current
      study examined serum levels of anti-Mullerian hormone (AMH), the most reliable
      endocrine marker for ovarian reserve, in early RA patients and the influence of
      disease activity and methotrexate (MTX) use on AMH concentrations. METHODS: Serum
      AMH levels were measured in 72 women with recent-onset RA ages 18-42 years and
      compared to 509 healthy women. The association between AMH and rheumatoid factor
      (RF), anti-cyclic citrullinated peptide (anti-CCP), erosions, C-reactive protein
      (CRP) level, disease activity (Disease Activity Score in 28 joints [DAS28]), and
      use of MTX was assessed. RESULTS: At diagnosis, age-adjusted serum AMH levels did
      not differ significantly between patients and controls (P = 0.254). AMH levels
      were not related to the presence of RF (P = 0.487), anti-CCP (P = 0.686), or
      erosions (P = 0.350), and showed no significant correlation with CRP levels (r = 
      0.207, P = 0.083) or disease activity scores (DAS28; r = 0.007, P = 0.955). After
      6 months of treatment, AMH levels in patients (n = 53) were lower than at the
      time of diagnosis (P < 0.001), but did not differ from controls (P = 0.741).
      There was no significant difference in AMH values after 6 months of treatment
      between patients who did (n = 31) or did not (n = 22) receive MTX (P = 0.287).
      CONCLUSION: AMH levels in women with early RA are comparable to those of healthy
      controls, indicating that the reduced fertility in this patient group is not
      caused by diminished ovarian reserve. AMH levels are not affected either by
      disease activity or by short-term MTX use.

PMID- 23554430
TI  - Distinct prestimulus and poststimulus activation of VTA neurons correlates with
      stimulus detection.
AB  - Dopamine neurons of the ventral tegmental area (VTA) signal the occurrence of a
      reward-predicting conditioned stimulus (CS) with a subsecond duration increase in
      post-CS firing rate. Important theories about reward-prediction error and reward
      expectancy have been informed by the substantial number of studies that have
      examined post-CS phasic VTA neuron activity. On the other hand, the role of VTA
      neurons in anticipation of a reward-predicting CS and analysis of prestimulus
      spike rate rarely has been studied. We recorded from the VTA in rats during the 3
      choice reaction time task, which has a fixed-duration prestimulus period and a
      difficult-to-detect stimulus. Use of a stimulus that was difficult to detect led
      to behavioral errors, which allowed us to compare VTA activity between trials
      with correct and incorrect stimulus-guided choices. We found a sustained increase
      in firing rate of both putative dopamine and GABA neurons during the pre-CS
      period of correct and incorrect trials. The poststimulus phasic response,
      however, was absent on incorrect trials, suggesting that the stimulus-evoked
      phasic response of dopamine neurons may relate to stimulus detection. The
      prestimulus activation of VTA neurons may modulate cortical systems that
      represent internal states of stimulus expectation and provide a mechanism for
      dopamine neurotransmission to influence preparatory attention to an expected
      stimulus. 

PMID- 23554431
TI  - Spontaneous oscillations in intrinsic signals reveal the structure of cerebral
      vasculature.
AB  - Functional imaging of intrinsic signals allows minimally invasive spatiotemporal
      mapping of stimulus representations in the cortex, but representations are often
      corrupted by stimulus-independent spatial artifacts, especially those originating
      from the blood vessels. In this paper, we present novel algorithms for
      unsupervised identification of cerebral vascularization, allowing blind
      separation of stimulus representations from noise. These algorithms commonly take
      advantage of the temporal fluctuations in global reflectance to extract anatomic
      information. More specifically, the phase of low-frequency oscillations relative
      to global fluctuations reveals local vascular identity. Arterioles can be
      reconstructed using their characteristically high power in those frequencies
      corresponding to respiration, heartbeat, and vasomotion signals. By treating the
      vasculature as a dynamic flow network, we finally demonstrate that direction of
      blood perfusion can be quantitatively visualized. Application of these methods
      for removal of stimulus-independent changes in reflectance permits isolation of
      stimulus-evoked representations even if the representation spatially overlaps
      with blood vessels. The algorithms can be expanded further to extract temporal
      information on blood flow, monitor revascularization following a focal stroke,
      and distinguish arterioles from venules and parenchyma.

PMID- 23554432
TI  - Differential regulation of synaptic transmission by pre- and postsynaptic SK
      channels in the spinal locomotor network.
AB  - The generation of activity in the central nervous system requires precise tuning
      of cellular properties and synaptic transmission. Neural networks in the spinal
      cord produce coordinated locomotor movements. Synapses in these networks need to
      be equipped with multiple mechanisms that regulate their operation over varying
      regimes to produce locomotor activity at different frequencies. Using the in
      vitro lamprey spinal cord, we explored whether Ca(2+) influx via different routes
      in postsynaptic soma and dendrites and in presynaptic terminals can activate
      apamin-sensitive Ca(2+)-activated K(+) (SK) channels and thereby shape synaptic
      transmission. We show that postsynaptic SK channels are tightly coupled to Ca(2+)
      influx via NMDA receptors. Activation of these channels by synaptically induced
      NMDA-dependent Ca(2+) transients restrains the time course of the synaptic
      current and the amplitude of the synaptic potential. In addition, presynaptic SK
      channels are activated by Ca(2+) influx via voltage-gated channels and control
      the waveform of the action potential and the resulting Ca(2+) dynamics in the
      axon terminals. The coupling of SK channels to different Ca(2+) sources, pre- and
      postsynaptically, acts as a negative feedback mechanism to shape synaptic
      transmission. Thus SK channels can play a pivotal role in setting the dynamic
      range of synapses and enabling short-term plasticity in the spinal locomotor
      network.

PMID- 23554433
TI  - Treadmill training promotes spinal changes leading to locomotor recovery after
      partial spinal cord injury in cats.
AB  - After a spinal hemisection at thoracic level in cats, the paretic hindlimb
      progressively recovers locomotion without treadmill training but asymmetries
      between hindlimbs persist for several weeks and can be seen even after a further
      complete spinal transection at T13. To promote optimal locomotor recovery after
      hemisection, such asymmetrical changes need to be corrected. In the present study
      we determined if the locomotor deficits induced by a spinal hemisection can be
      corrected by locomotor training and, if so, whether the spinal stepping after the
      complete spinal cord transection is also more symmetrical. This would indicate
      that locomotor training in the hemisected period induces efficient changes in the
      spinal cord itself. Sixteen adult cats were first submitted to a spinal
      hemisection at T10. One group received 3 wk of treadmill training, whereas the
      second group did not. Detailed kinematic and electromyographic analyses showed
      that a 3-wk period of locomotor training was sufficient to improve the quality
      and symmetry of walking of the hindlimbs. Moreover, after the complete spinal
      lesion was performed, all the trained cats reexpressed bilateral and symmetrical
      hindlimb locomotion within 24 h. By contrast, the locomotor pattern of the
      untrained cats remained asymmetrical, and the hindlimb on the side of the
      hemisection was still deficient. This study highlights the beneficial role of
      locomotor training in facilitating bilateral and symmetrical functional plastic
      changes within the spinal circuitry and in promoting locomotor recovery after an
      incomplete spinal cord injury.

PMID- 23554434
TI  - Motor unit rate coding is severely impaired during forceful and fast muscular
      contractions in individuals post stroke.
AB  - Information regarding how motor units are controlled to produce forces in
      individuals with stroke and the mechanisms behind muscle weakness and movement
      slowness can potentially inform rehabilitation strategies. The purpose of this
      study was to describe the rate coding mechanism in individuals poststroke during
      both constant (n = 8) and rapid (n = 4) force production tasks. Isometric ankle
      dorsiflexion force, motor unit action potentials, and surface electromyography
      were recorded from the paretic and nonparetic tibialis anterior. In the paretic
      limb, strength was 38% less and the rate of force development was 63% slower.
      Linear regression was used to describe and compare the relationships between
      motor unit and electromyogram (EMG) measures and force. During constant force
      contractions up to 80% maximal voluntary contraction (MVC), rate coding was
      compressed and discharge rates were lower in the paretic limb. During rapid
      muscle contractions up to 90% MVC, the first interspike interval was prolonged
      and the rate of EMG rise was less in the paretic limb. Future rehabilitation
      strategies for individuals with stroke could focus on regaining these specific
      aspects of motor unit rate coding and neuromuscular activation.

PMID- 23554435
TI  - Grasping uncertainty: effects of sensorimotor memories on high-level planning of
      dexterous manipulation.
AB  - For successful object manipulation, the central nervous system must appropriately
      coordinate digit placement and force distribution. It is known that digit force
      planning is significantly influenced by previous manipulations even when object
      properties cannot be predicted on a trial-to-trial basis. We sought to determine
      whether this effect extends beyond force control to the coordination of digit
      placement and force. Subjects grasped and lifted an object whose center of mass
      (CM) was changed unpredictably across trials. Grasp planning was quantified by
      measuring the torque generated on the object at lift onset. We found that both
      digit placement and force were systematically affected by the CM experienced on
      the previous trial. Additionally, the negative covariation between digit forces
      and positions typically found for predictable CM presentations was also found for
      unpredictable CM trials. A follow-up experiment revealed that these effects were
      not dependent on visual feedback of object roll during object lift on the
      previous trial. We conclude that somatosensory feedback from previous grasp
      experience alone can affect high-level grasp planning by constraining the
      relation between digit force and position even when the task behavioral
      consequences cannot be reliably predicted. As learning of manipulations often
      involves interactions with objects in novel environments, the present findings
      are an important step to understanding the control strategies associated with the
      integration of sensorimotor memories and motor planning.

PMID- 23554436
TI  - Potassium conductance dynamics confer robust spike-time precision in a
      neuromorphic model of the auditory brain stem.
AB  - A fundamental question in neuroscience is how neurons perform precise operations
      despite inherent variability. This question also applies to neuromorphic
      engineering, where low-power microchips emulate the brain using large populations
      of diverse silicon neurons. Biological neurons in the auditory pathway display
      precise spike timing, critical for sound localization and interpretation of
      complex waveforms such as speech, even though they are a heterogeneous
      population. Silicon neurons are also heterogeneous, due to a key design
      constraint in neuromorphic engineering: smaller transistors offer lower power
      consumption and more neurons per unit area of silicon, but also more variability
      between transistors and thus between silicon neurons. Utilizing this variability
      in a neuromorphic model of the auditory brain stem with 1,080 silicon neurons, we
      found that a low-voltage-activated potassium conductance (g(KL)) enables precise
      spike timing via two mechanisms: statically reducing the resting membrane time
      constant and dynamically suppressing late synaptic inputs. The relative
      contribution of these two mechanisms is unknown because blocking g(KL) in vitro
      eliminates dynamic adaptation but also lengthens the membrane time constant. We
      replaced g(KL) with a static leak in silico to recover the short membrane time
      constant and found that silicon neurons could mimic the spike-time precision of
      their biological counterparts, but only over a narrow range of stimulus
      intensities and biophysical parameters. The dynamics of g(KL) were required for
      precise spike timing robust to stimulus variation across a heterogeneous
      population of silicon neurons, thus explaining how neural and neuromorphic
      systems may perform precise operations despite inherent variability.

PMID- 23554437
TI  - Optimal control of reaching includes kinematic constraints.
AB  - We investigate adaptation under a reaching task with an acceleration-based force
      field perturbation designed to alter the nominal straight hand trajectory in a
      potentially benign manner: pushing the hand off course in one direction before
      subsequently restoring towards the target. In this particular task, an explicit
      strategy to reduce motor effort requires a distinct deviation from the nominal
      rectilinear hand trajectory. Rather, our results display a clear directional
      preference during learning, as subjects adapted perturbed curved trajectories
      towards their initial baselines. We model this behavior using the framework of
      stochastic optimal control theory and an objective function that trades off the
      discordant requirements of 1) target accuracy, 2) motor effort, and 3) kinematic
      invariance. Our work addresses the underlying objective of a reaching movement,
      and we suggest that robustness, particularly against internal model uncertainly,
      is as essential to the reaching task as terminal accuracy and energy efficiency. 

PMID- 23554438
TI  - Linear summation in the barn owl's brainstem underlies responses to interaural
      time differences.
AB  - The neurophonic potential is a synchronized frequency-following extracellular
      field potential that can be recorded in the nucleus laminaris (NL) in the
      brainstem of the barn owl. Putative generators of the neurophonic are the
      afferent axons from the nucleus magnocellularis, synapses onto NL neurons, and
      spikes of NL neurons. The outputs of NL, i.e., action potentials of NL neurons,
      are only weakly represented in the neurophonic. Instead, the inputs to NL, i.e.,
      afferent axons and their synaptic potentials, are the predominant origin of the
      neurophonic (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol
      104: 2274-2290, 2010). Thus in NL the monaural inputs from the two brain sides
      converge and create a binaural neurophonic. If these monaural inputs contribute
      independently to the extracellular field, the response to binaural stimulation
      can be predicted from the sum of the responses to ipsi- and contralateral
      stimulation. We found that a linear summation model explains the dependence of
      the responses on interaural time difference as measured experimentally with
      binaural stimulation. The fit between model predictions and data was excellent,
      even without taking into account the nonlinear responses of NL coincidence
      detector neurons, although their firing rate and synchrony strongly depend on the
      interaural time difference. These results are consistent with the view that the
      afferent axons and their synaptic potentials in NL are the primary origin of the
      neurophonic. 

PMID- 23554440
TI  - Oxygen therapy in acute coronary syndrome: are the benefits worth the risk?
AB  - Oxygen supplementation is a standard treatment for all patients who present with
      acute coronary syndrome, regardless of oxygen saturation levels. Most of the data
      regarding the function of oxygen in myocardial infarction is based on a limited
      number of basic and clinical studies. We performed a systematic literature review
      that explores the basic and clinical data on the function of oxygen in ischaemic
      heart disease and myocardial infarction. This review discusses many aspects of
      oxygen treatment: (i) basic studies on the effects of oxygen in ischaemia and the
      potential cardiovascular effects of oxygen metabolites; (ii) clinical trials that
      have assessed the value of inhaled oxygen, supersaturated oxygen, and
      intracoronary injection of hyperoxaemic solutions in myocardial infarction; and
      (iii) the haemodynamic effects of oxygen in various clinical scenarios and its
      direct effects on the coronary vasculature. Our findings suggest that there are
      conflicting data on the effects of oxygen treatment. Further, the potential
      harmful effects of oxygen must be considered, particularly in myocardial
      infarction. These findings question the current guidelines and recommendations
      and emphasize the need for large clinical trials.

PMID- 23554441
TI  - A patient with ischaemic cardiomyopathy.

PMID- 23554442
TI  - The importance of normative integration in stroke services: case study evidence
      from Sweden and England.
AB  - OBJECTIVES: A number of evidence-based interventions are now available for stroke
      patients. Good-quality stroke care involves a range of health professionals
      located across ambulance, hospital, community and primary care services. This
      study examined the perspectives of health-care workers involved in stroke care in
      Sweden and England on the integration challenges stroke care presents. METHODS:
      Four qualitative case studies were carried out in Sweden and England, including
      95 semistructured interviews with clinicians and managers associated with four
      different hospitals providing specialized stroke services. FINDINGS: High levels
      of organizational, functional, service and clinical integration among clinicians
      that deliver emergency and acute stroke care were identified. This is frequently
      lacking among professionals delivering postacute care. These findings are linked
      to the prevalence or lack of normative and systemic integration in each
      respective stage of care. CONCLUSIONS: Emphasis on the need to treat stroke as an
      emergency condition in both countries has created a context in which normative
      and systemic integration often occurs among clinicians that deliver emergency and
      acute stroke care, aiding the development of organizational, functional, service
      and clinical integration across the case study sites. In contrast, integration
      between hospital and community (rehabilitation and general practice) care is
      frequently less successful.

PMID- 23554443
TI  - Utilizing experience-based co-design to improve the experience of patients
      accessing emergency departments in New South Wales public hospitals: an
      evaluation study.
AB  - BACKGROUND: This paper presents the findings of three multisite evaluations of
      Experience-Based Co-design (EBCD) programmes conducted in Emergency Departments
      (EDs) and associated departments in seven public hospitals in New South Wales,
      Australia. METHOD: Data for the evaluations were derived from: EBCD documentation
      provided by the participating sites; interviews with 117 key informants;
      performance data and the policy and academic literature on EBCD. RESULTS:
      Respondents described EBCD as a successful and sustainable method of improving
      the individual patient experience and the overall quality of a health service.
      Demonstrated successes were reported to lead to aspects of the EBCD approach
      spreading within services. However, like any quality improvement activity, EBCD
      was not without its challenges. The principal challenge particular to the EBCD
      projects outlined here was their deployment in ED settings. Because of their
      ambulant patient populations, these settings made sustaining consumer engagement
      for the duration of the project problematic and required tailoring EBCD to
      accommodate consumers' involvement preferences and constraints. CONCLUSION: The
      primary strength of EBCD over and above other service development methodologies
      was reported to be its ability to bring about improvements simultaneously in both
      the operational efficiency and the inter-personal dynamics of care. However,
      careful consideration must be given to the constraints inherent in transient
      patient specialties and what needs to be done to tailor EBCD to suit the
      particular setting in which it is deployed.

PMID- 23554444
TI  - Effect of cost efficiency reporting on utilization by physician specialists: a
      difference-in-difference study.
AB  - OBJECTIVE: To assess whether health plan implementation of specialist profile
      reports not associated with any health plan administered reward or consequence
      that measured physician cost efficiency relative to peers, and shared with
      specialists and primary care referral sources only, were associated with changes
      in specialist behaviour. DATA SOURCE/STUDY SETTING: Blue Care Network of Michigan
      is a non-profit statewide Health Maintenance Organization and wholly owned
      subsidiary of Blue Cross Blue Shield of Michigan. This study used administrative
      data from 2002 to 2006 and included only providers and adult (ages 18-65)
      commercial membership located in Southeastern Michigan. STUDY DESIGN: A
      difference-in-difference study design of before and after specialist cost
      efficiency reporting on six specialties to both specialists and primary care
      referral sources, but not health plan members, to determine whether specialists
      who performed worse than peers changed the level of utilization of their own
      physician services without any direct health plan reward or consequence.
      PRINCIPAL FINDINGS: Substantive changes were noted for interventional cardiology
      (-32.3%, P <= 0.01), orthopaedics (-13.3%, P <= 0.01) and otolaryngology (-15.9%,
      P <= 0.02). Less established, yet negative changes were noted for ophthalmology (
      11.9%, P <= 0.01), gastroenterology (-3.2%, P = 0.23) and urology (-3.1%, P =
      0.52). CONCLUSIONS: Simple and transparent reports on specialist cost efficiency
      distributed to referral sources and specialists using a more laissez-faire style
      reporting only health plan programme can engage providers and be associated with
      reductions in utilization. Possible mechanisms include explicit pressure from
      referral sources or self-motivated change by specialists.

PMID- 23554445
TI  - Innovation sustainability in challenging health-care contexts: embedding
      clinically led change in routine practice.
AB  - The need for organizational innovation as a means of improving health-care
      quality and containing costs is widely recognized, but while a growing body of
      research has improved knowledge of implementation, very little has considered the
      challenges involved in sustaining change - especially organizational change led
      'bottom-up' by frontline clinicians. This study addresses this lacuna, taking a
      longitudinal, qualitative case-study approach to understanding the paths to
      sustainability of four organizational innovations. It highlights the importance
      of the interaction between organizational context, nature of the innovation and
      strategies deployed in achieving sustainability. It discusses how positional
      influence of service leads, complexity of innovation, networks of support,
      embedding in existing systems, and proactive responses to changing circumstances
      can interact to sustain change. In the absence of cast-iron evidence of
      effectiveness, wider notions of value may be successfully invoked to sustain
      innovation. Sustainability requires continuing effort through time, rather than
      representing a final state to be achieved. Our study offers new insights into the
      process of sustainability of organizational change, and elucidates the complement
      of strategies needed to make bottom-up change last in challenging contexts
      replete with competing priorities.

PMID- 23554447
TI  - Cisplatin resistance associated with PARP hyperactivation.
AB  - Non-small cell lung carcinoma patients are frequently treated with cisplatin
      (CDDP), most often yielding temporary clinical responses. Here, we show that
      PARP1 is highly expressed and constitutively hyperactivated in a majority of
      human CDDP-resistant cancer cells of distinct histologic origin. Cells
      manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins
      (PAR(high)) responded to pharmacologic PARP inhibitors as well as to PARP1
      targeting siRNAs by initiating a DNA damage response that translated into cell
      death following the activation of the intrinsic pathway of apoptosis. Moreover,
      PARP1-overexpressing tumor cells and xenografts displayed elevated levels of PAR,
      which predicted the response to PARP inhibitors in vitro and in vivo more
      accurately than PARP1 expression itself. Thus, a majority of CDDP-resistant
      cancer cells appear to develop a dependency to PARP1, becoming susceptible to
      PARP inhibitor-induced apoptosis.

PMID- 23554448
TI  - Crimping and deployment of balloon-expandable valved stents are responsible for
      the increase in the hydraulic conductance of leaflets.
AB  - OBJECTIVES: Leaflet injury has been documented to occur during the deployment of
      valved stents (VSs). The pathological aspects, however, of this injury are
      difficult to quantify. Conversely, the hydraulic conductance of a (pericardial)
      membrane may be easily determined. The impact of crimping and deployment of VS on
      this parameter was therefore investigated. METHODS: Bovine pericardial square (25
      * 25 mm) patches were placed within a pressure chamber and their hydraulic
      conductance was determined. The influence of the pressure gradient and tissue
      thickness on this parameter was analysed. Six balloon-expandable VS were
      constructed. The hydraulic conductance of their bovine pericardial leaflets was
      determined before and after VS crimping and deployment in four of them.
      Pericardial leaflets of non-crimped VS were used as controls. RESULTS: Hydraulic
      conductance increased insignificantly with the pressure level within the chamber:
      from 128 +/- 26.9 ml/h/m(2)/mmHg at a pressure of 50 mmHg to 232.3 +/- 51.9
      ml/h/m(2)/mmHg at a pressure of 250 mmHg (P = 0.117). Hydraulic conductance was
      not correlated to pericardial thickness, for thickness measurements ranging from
      0.34 to 0.76 mm. The hydraulic conductance of VS leaflets significantly increased
      immediately after crimping from 45.2 +/- 7.6 to 667.9.0 +/- 527.2 ml/h/m(2)/mmHg
      (P < 0.001). This increase was still observed 24 h after VS deployment. No change
      in hydraulic conductance occurred in the control group. CONCLUSIONS: The
      determination of the hydraulic conductance of pericardial patches was easy to
      perform, reproducible and not influenced by tissue thickness. The hydraulic
      conductance of pericardial leaflets dramatically increased after VS crimping and
      deployment. This parameter might be, in the future, a useful noninvasive tool in
      studying leaflet trauma.

PMID- 23554449
TI  - The oncological value of video-assisted thoracoscopic lobectomy for early-stage
      non-small-cell lung cancer.

PMID- 23554450
TI  - A thyroxine absorption test followed by weekly thyroxine administration: a method
      to assess non-adherence to treatment.
AB  - OBJECTIVE: For patients who remain hypothyroid despite the administration of what
      would seem adequate doses of levothyroxine (L-T4), the underlying cause can be
      difficult to determine. The possibility of a biological cause should first be
      explored; however, in the majority of cases, poor adherence to medication is
      likely to be the main cause of treatment failure. When non-adherence is suspected
      but not volunteered, options to confirm the suspicion are limited. In this study,
      we identified patients for whom known drugs and pathological causes of L-T4
      malabsorption were excluded, and despite often high doses of L-T4, the patients
      remained hypothyroid. DESIGN: Using a weight-determined oral L-T4 bolus
      administration, absorption was initially assessed in 23 patients. In nearly all
      patients, this was shown to be maximal at 120 min post-ingestion. This was then
      followed by the continued administration of a weekly T4 bolus for a 4-week period
      after which TSH and free T4 (fT4) levels were recorded. RESULTS: All patients
      showed a rise in fT4 at 120 min following the administration of the L-T4 bolus,
      with a mean increase of 54+/-3% from baseline. Following the treatment period,
      using an equivalent weekly L-T4 dose, which was significantly less than that of
      the daily dose taken by the patients before the test, TSH reduced from baseline
      in ~75% of cases. CONCLUSION: Using this combination of tests allows significant
      malabsorptive problems to be identified first and then potential non-adherence to
      be demonstrated. A management plan can then be implemented to increase adherence,
      aiming to improve treatment outcomes.

PMID- 23554452
TI  - Cardiac expression of deiodinase type 3 (Dio3) following myocardial infarction is
      associated with the induction of a pluripotency microRNA signature from the Dlk1
      Dio3 genomic region.
AB  - The adult heart has almost completely lost the proliferative potential of the
      fetal heart. Instead, loss of cardiomyocytes due to myocardial infarction (MI)
      leads to a limited, and often insufficient, hypertrophic response of
      cardiomyocytes in the spared myocardium. This response is still characterized by
      a partial reexpression of the fetal gene program. Because of the suggested
      involvement of microRNAs (miRNAs) in cardiac remodeling, we examined the miRNA
      expression profile of the spared left ventricular myocardium using a MI mouse
      model. C57Bl/6J mice of either sex were randomly assigned to the sham-operated
      group or MI group. MI was induced by ligation of the left coronary artery. One
      week after surgery RNA was isolated from the left ventricle. MiRNA analysis was
      performed using the Taqman Megaplex rodent array. Unexpectedly, we found a set of
      29 up-regulated miRNAs originating from the Dlk1-Dio3 genomic imprinted region,
      which has been identified as a hallmark of pluripotency and proliferation. This
      miRNA signature was associated with a 6-fold increase in expression of the
      deiodinase type 3 gene (Dio3) located in this region. Dio3 is a fetally expressed
      thyroid hormone-inactivating enzyme associated with cell proliferation, which was
      shown to be up-regulated in cardiomyocytes creating a local hypothyroid condition
      in the spared myocardium in this model. These data suggest that a regenerative
      process is initiated, but not completed, in adult cardiomyocytes after MI. The
      identified miRNA signature could provide new ways to manipulate the in vivo
      response of adult cardiomyocytes to stress and to increase the regenerative
      capacity of the injured myocardium.

PMID- 23554453
TI  - Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone
      sulfate and dehydroepiandrosterone sulfate in the hypothalamus.
AB  - The sulfated neurosteroids pregnenolone sulfate (Delta(5)PS) and
      dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of
      reproductive behavior. In the frog Pelophylax ridibundus, the enzyme
      hydroxysteroid sulfotransferase (HST), responsible for the biosynthesis of
      Delta(5)PS and DHEAS, is expressed in the magnocellular nucleus and the anterior
      preoptic area, two hypothalamic regions that are richly innervated by GnRH1
      containing fibers. This observation suggests that GnRH1 may regulate the
      formation of sulfated neurosteroids to control sexual activity. Double labeling
      of frog brain slices with HST and GnRH1 antibodies revealed that GnRH1
      immunoreactive fibers are located in close vicinity of HST-positive neurons. The
      cDNAs encoding 3 GnRH receptors (designated riGnRHR-1, -2, and -3) were cloned
      from the frog brain. RT-PCR analyses revealed that riGnRHR-1 is strongly
      expressed in the hypothalamus and the pituitary whereas riGnRHR-2 and -3 are
      primarily expressed in the brain. In situ hybridization histochemistry indicated
      that GnRHR-1 and GnRHR-3 mRNAs are particularly abundant in preoptic area and
      magnocellular nucleus whereas the concentration of GnRHR-2 mRNA in these 2 nuclei
      is much lower. Pulse-chase experiments using tritiated Delta(5)P and DHEA as
      steroid precursors, and 3'-phosphoadenosine 5'-phosphosulfate as a sulfonate
      moiety donor, showed that GnRH1 stimulates, in a dose-dependent manner, the
      biosynthesis of Delta(5)PS and DHEAS in frog diencephalic explants. Because
      Delta(5)PS and DHEAS, like GnRH, stimulate sexual activity, our data strongly
      suggest that some of the behavioral effects of GnRH could be mediated via the
      modulation of sulfated neurosteroid production.

PMID- 23554451
TI  - Notch signaling in skeletal health and disease.
AB  - Notch receptors are single-pass transmembrane proteins that determine cell fate.
      Upon Notch ligand interactions, proteolytic cleavages release the Notch
      intracellular domain, which translocates to the nucleus to regulate the
      transcription of target genes, including Hairy enhancer of split (Hes) and Hes
      related to YRPW motif (Hey). Notch is critical for skeletal development and
      activity of skeletal cells, and dysregulation of Notch signaling is associated
      with human diseases affecting the skeleton. Inherited or sporadic mutations in
      components of the Notch signaling pathway are associated with spondylocostal
      dysostosis, spondylothoracic dysostosis and recessive brachydactyly, diseases
      characterized by skeletal patterning defects. Inactivating mutations of the Notch
      ligand JAG1 or of NOTCH2 are associated with Alagille syndrome, and activating
      mutations in NOTCH2 are associated with Hajdu-Cheney syndrome (HCS). Individuals
      affected by HCS exhibit osteolysis in distal phalanges and osteoporosis. NOTCH is
      activated in selected tumors, such as osteosarcoma, and in breast cancer cells
      that form osteolytic bone metastases. In conclusion, Notch regulates skeletal
      development and bone remodeling, and gain- or loss-of-function mutations of Notch
      signaling result in important skeletal diseases.

PMID- 23554455
TI  - Public accessibility of biomedical articles from PubMed Central reduces journal
      readership--retrospective cohort analysis.
AB  - Does PubMed Central--a government-run digital archive of biomedical articles-
      compete with scientific society journals? A longitudinal, retrospective cohort
      analysis of 13,223 articles (5999 treatment, 7224 control) published in 14
      society-run biomedical research journals in nutrition, experimental biology,
      physiology, and radiology between February 2008 and January 2011 reveals a 21.4%
      reduction in full-text hypertext markup language (HTML) article downloads and a
      13.8% reduction in portable document format (PDF) article downloads from the
      journals' websites when U.S. National Institutes of Health-sponsored articles
      (treatment) become freely available from the PubMed Central repository. In
      addition, the effect of PubMed Central on reducing PDF article downloads is
      increasing over time, growing at a rate of 1.6% per year. There was no
      longitudinal effect for full-text HTML downloads. While PubMed Central may be
      providing complementary access to readers traditionally underserved by scientific
      journals, the loss of article readership from the journal website may weaken the
      ability of the journal to build communities of interest around research papers,
      impede the communication of news and events to scientific society members and
      journal readers, and reduce the perceived value of the journal to institutional
      subscribers.

PMID- 23554454
TI  - Roux-en-Y gastric bypass surgery but not vertical sleeve gastrectomy decreases
      bone mass in male rats.
AB  - The most effective treatment for obesity is bariatric surgery. However, there is
      increasing concern that bariatric surgery can cause nutrient deficiencies that
      translate into metabolic bone disease. Whether this is true for all surgery types
      is not yet clear. We therefore investigated the effects of 2 commonly applied
      bariatric surgeries (Roux-en-Y gastric bypass [RYGB] and vertical sleeve
      gastrectomy) on energy and bone metabolism in rats 60 days after surgery. Both
      surgeries resulted in similar reductions of body weight, body fat, and food
      intake. Glucose tolerance was improved to a similar extent after both surgeries
      and was accompanied by increased postprandial secretion of glucose-dependent
      insulinotropic peptide. Using microcomputed tomography, we found that, relative
      to sham-operated rats, bone volume was significantly reduced after RYGB but not
      vertical sleeve gastrectomy. RYGB rats also had markedly reduced lipid absorption
      from the intestine and significantly lower serum 25-hydroxyvitamin D and calcium
      levels. Importantly, dietary supplementation with calcium and vitamin D could not
      fully rescue the reduced bone volume after RYGB surgery. Both surgeries resulted
      in a significant increase in stomach pH, which may have worsened the
      malabsorption in RYGB rats. Our findings suggest that bone loss in RYGB rats is
      not exclusively driven by calcium and vitamin D malabsorption but also by
      additional factors that may not be rescuable by dietary supplementation. These
      data point toward important similarities and differences between bariatric
      procedures that should be considered in clinical settings as guidance for which
      procedure will be best for specific patient populations.

PMID- 23554456
TI  - T-tubules and ryanodine receptor microdomains: on the road to translation.

PMID- 23554458
TI  - Cardioprotection by the TSPO ligand 4'-chlorodiazepam is associated with
      inhibition of mitochondrial accumulation of cholesterol at reperfusion.
AB  - AIMS: The translocator protein (TSPO) is located on the outer mitochondrial
      membrane where it is responsible for the uptake of cholesterol into mitochondria
      of steroidogenic organs. TSPO is also present in the heart where its role remains
      uncertain. We recently showed that TSPO ligands reduced infarct size and improved
      mitochondrial functions after ischaemia-reperfusion. This study, thus, sought to
      determine whether cholesterol could play a role in the cardioprotective effect of
      TSPO ligands. METHODS AND RESULTS: In a model of 30 min coronary occlusion/15 min
      reperfusion in Wistar rat, we showed that reperfusion induced lipid peroxidation
      as demonstrated by the increase in conjugated diene and thiobarbituric acid
      reactive substance formation and altered mitochondrial function (decrease in
      oxidative phosphorylation and increase in the sensitivity of mitochondrial
      permeability transition pore opening) in ex-vivo isolated mitochondria. This was
      associated with an increase in mitochondrial cholesterol uptake (89.5 +/- 12.2
      vs. 39.9 +/- 3.51 nmol/mg protein in controls, P < 0.01) and a subsequent strong
      generation of auto-oxidized oxysterols, i.e. 7alpha- and 7beta
      hydroxycholesterol, 7-ketocholesterol, cholesterol-5alpha,6alpha-epoxide, and
      5beta,6beta-epoxide (+173, +149, +165, +165, and +193% vs. controls,
      respectively; P < 0.01). Administration of the selective TSPO ligand 4'
      chlorodiazepam inhibited oxidative stress, improved mitochondrial function, and
      abolished both mitochondrial cholesterol accumulation and oxysterol production.
      This was also observed with the new TSPO ligand TRO40303. CONCLUSION: These data
      suggest that 4'-chlorodiazepam inhibits oxidative stress and oxysterol formation
      by reducing the accumulation of cholesterol in the mitochondrial matrix at
      reperfusion and prevents mitochondrial injury. This new and original mechanism
      may contribute to the cardioprotective properties of TSPO ligands.

PMID- 23554457
TI  - TGF-beta signalling and reactive oxygen species drive fibrosis and matrix
      remodelling in myxomatous mitral valves.
AB  - AIMS: Myxomatous mitral valve disease (MMVD) is associated with leaflet
      thickening, fibrosis, matrix remodelling, and leaflet prolapse. Molecular
      mechanisms contributing to MMVD, however, remain poorly understood. We tested the
      hypothesis that increased transforming growth factor-beta (TGF-beta) signalling
      and reactive oxygen species (ROS) are major contributors to pro-fibrotic gene
      expression in human and mouse mitral valves. METHODS AND RESULTS: Using qRT-PCR,
      we found that increased expression of TGF-beta1 in mitral valves from humans with
      MMVD (n = 24) was associated with increased expression of connective tissue
      growth factor (CTGF) and matrix metalloproteinase 2 (MMP2). Increased levels of
      phospho-SMAD2/3 (western blotting) and expression of SMAD-specific E3 ubiquitin
      protein ligases (SMURF) 1 and 2 (qRT-PCR) suggested that TGF-beta1 signalling
      occurred through canonical signalling cascades. Oxidative stress (dihydroethidium
      staining) was increased in human MMVD tissue and associated with increases in
      NAD(P)H oxidase catalytic subunits (Nox) 2 and 4, occurring despite increases in
      superoxide dismutase 1 (SOD1). In mitral valves from SOD1-deficient mice,
      expression of CTGF, MMP2, Nox2, and Nox4 was significantly increased, suggesting
      that ROS can independently activate pro-fibrotic and matrix remodelling gene
      expression patterns. Furthermore, treatment of mouse mitral valve interstitial
      cells with cell permeable antioxidants attenuated TGF-beta1-induced pro-fibrotic
      and matrix remodelling gene expression in vitro. CONCLUSION: Activation of
      canonical TGF-beta signalling is a major contributor to fibrosis and matrix
      remodelling in MMVD, and is amplified by increases in oxidative stress.
      Treatments aimed at reducing TGF-beta activation and oxidative stress in early
      MMVD may slow progression of MMVD.

PMID- 23554459
TI  - MicroRNA-638 is highly expressed in human vascular smooth muscle cells and
      inhibits PDGF-BB-induced cell proliferation and migration through targeting
      orphan nuclear receptor NOR1.
AB  - AIMS: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration
      contribute significantly to the development of vascular pathologies, such as
      atherosclerosis and restenosis. MicroRNAs have recently emerged as critical
      modulators in cellular processes and the purpose of this study is to identify
      novel miRNA regulators implicated in human aortic VSMC proliferation and
      migration. METHODS AND RESULTS: To identify miRNAs that are differentially
      expressed in human VSMCs, we performed miRNA microarray analysis in human aortic
      smooth muscle cells (SMCs) at different time points after platelet-derived growth
      factor (PDGF) stimulation. Here, we identified microRNA-638 (miR-638) as a
      transcript that was one of the most significantly down-regulated in human VSMCs
      after PDGF stimulation. Furthermore, we confirmed, by Quantitative RT-PCR, that
      miR-638 is highly expressed in human VSMCs, and its expression is markedly down
      regulated in a dose- and time-dependent manner upon PDGF treatment. Consistent
      with a critical role in SMC proliferation, we found that miR-638 expression was
      significantly up-regulated in human VSMCs cultured in differentiation medium, a
      condition that inhibits SMC proliferation. Furthermore, we identified the orphan
      nuclear receptor NOR1 as a downstream target gene product of miR-638 and down
      regulation of NOR1 is critical for miR-638-mediated inhibitory effects on PDGF
      induced cyclin D1 expression, cell proliferation, and migration in human aortic
      SMCs. CONCLUSION: These results indicate that miR-638 is a key molecule in
      regulating human VSMC proliferation and migration by targeting the NOR1/cyclin D
      pathway and suggest that specific modulation of miR-638 in human VSMCs may
      represent an attractive approach for the treatment of proliferative vascular
      diseases.

PMID- 23554460
TI  - Aerobic interval training attenuates remodelling and mitochondrial dysfunction in
      the post-infarction failing rat heart.
AB  - AIMS: Following a large myocardial infarction (MI), remaining viable muscle often
      undergoes pathological remodelling and progresses towards chronic heart failure.
      Mitochondria may also be affected by this process and, due to their functional
      importance, likely contribute to the progression of the disease. Aerobic interval
      training (AIT) has been shown effective in diminishing pathological myocardial
      transformation, but the effects of AIT on mitochondrial function in hearts
      undergoing remodelling are not known. METHODS AND RESULTS: Adult female Sprague
      Dawley rats were randomized to either 8 weeks of aerobic interval treadmill
      running (5 days/week), which started 4 weeks after left coronary artery ligation
      (MI-Trained), or a sedentary group (MI-Sedentary). Echocardiography was performed
      before and after the 8-week period, at which point the left ventricles (LVs) were
      also harvested. Twelve weeks after surgery, MI-Sedentary rats had significantly
      lower LV fractional shortening compared with MI-Trained rats. Complex I-dependent
      respiration assessed in isolated LV mitochondria was decreased by ~37% in MI
      Sedentary and 17% in MI-Trained animals (group differences P < 0.05), compared
      with sham-operated animals. This was paralleled with diminished ATP production
      and increased degree of protein oxidation in MI-Sedentary rats. The enzymatic
      activity of complex I was also decreased to a greater extent in MI-Sedentary than
      in MI-Trained animals, with no evidence of its reduced expression. When complex
      II substrate was used, no differences among the three groups were observed.
      CONCLUSION: Exercise reduces LV contractile deterioration in post-infarction
      heart failure and alleviates the extent of mitochondrial dysfunction, which is
      paralleled with preserved complex I activity.

PMID- 23554461
TI  - Increasing short-term cardiomyocyte progenitor cell (CMPC) survival by
      necrostatin-1 did not further preserve cardiac function.
AB  - AIMS: One of the main limitations for an effective cell therapy for the heart is
      the poor cell engraftment after implantation, which is partly due to a large
      percentage of cell death in the hostile myocardium. In the present study, we
      investigated the utilization of necrostatin-1 (Nec-1) as a possible attenuator of
      cell death in cardiomyocyte progenitor cells (CMPCs). METHODS AND RESULTS: In a
      mouse model of myocardial infarction, survival of CMPCs 3 days after intra
      myocardial injection was 39 +/- 9% higher in cells pretreated with the Nec-1
      compound. However, the increase in cell number was not sustained over 28 days,
      and did not translate into improved cardiac function (ejection fraction %, 20.6
      +/- 2.1 vs. 21.4 +/- 2.5 for vehicle and Nec-1-treated CMPC, respectively).
      Nonetheless, Nec-1 rescued CMPCs remained functionally competent. CONCLUSION: A
      pharmacological pretreatment approach to solely enhance cell survival on the
      short term does not seem to be effective strategy to improve cardiac cell therapy
      with CMPCs.

PMID- 23554462
TI  - Inferring chromatin-bound protein complexes from genome-wide binding assays.
AB  - Genome-wide binding assays can determine where individual transcription factors
      bind in the genome. However, these factors rarely bind chromatin alone, but
      instead frequently bind to cis-regulatory elements (CREs) together with other
      factors thus forming protein complexes. Currently there are no integrative
      analytical approaches that can predict which complexes are formed on chromatin.
      Here, we describe a computational methodology to systematically capture protein
      complexes and infer their impact on gene expression. We applied our method to
      three human cell types, identified thousands of CREs, inferred known and
      undescribed complexes recruited to these CREs, and determined the role of the
      complexes as activators or repressors. Importantly, we found that the predicted
      complexes have a higher number of physical interactions between their members
      than expected by chance. Our work provides a mechanism for developing hypotheses
      about gene regulation via binding partners, and deciphering the interplay between
      combinatorial binding and gene expression. 

PMID- 23554463
TI  - Comprehensive prediction in 78 human cell lines reveals rigidity and compactness
      of transcription factor dimers.
AB  - The binding of transcription factors (TFs) to their specific motifs in genomic
      regulatory regions is commonly studied in isolation. However, in order to
      elucidate the mechanisms of transcriptional regulation, it is essential to
      determine which TFs bind DNA cooperatively as dimers and to infer the precise
      nature of these interactions. So far, only a small number of such dimeric
      complexes are known. Here, we present an algorithm for predicting cell-type
      specific TF-TF dimerization on DNA on a large scale, using DNase I
      hypersensitivity data from 78 human cell lines. We represented the universe of
      possible TF complexes by their corresponding motif complexes, and analyzed their
      occurrence at cell-type-specific DNase I hypersensitive sites. Based on ~1.4
      billion tests for motif complex enrichment, we predicted 603 highly significant
      cell-type-specific TF dimers, the vast majority of which are novel. Our
      predictions included 76% (19/25) of the known dimeric complexes and showed
      significant overlap with an experimental database of protein-protein
      interactions. They were also independently supported by evolutionary
      conservation, as well as quantitative variation in DNase I digestion patterns.
      Notably, the known and predicted TF dimers were almost always highly compact and
      rigidly spaced, suggesting that TFs dimerize in close proximity to their
      partners, which results in strict constraints on the structure of the DNA-bound
      complex. Overall, our results indicate that chromatin openness profiles are
      highly predictive of cell-type-specific TF-TF interactions. Moreover, cooperative
      TF dimerization seems to be a widespread phenomenon, with multiple TF complexes
      predicted in most cell types. 

PMID- 23554464
TI  - Seafood types and age-related cognitive decline in the Women's Health Study.
AB  - BACKGROUND: Seafood consumption may prevent age-related cognitive decline.
      However, benefits may vary by nutrient contents in different seafood types. We
      examined associations between total seafood consumption and cognitive decline and
      whether these associations differ by seafood types. METHODS: We conducted a
      prospective cohort study of 5,988 women (mean age, 72 years) from the Women's
      Health Study who self-reported seafood intake at Women's Health Study baseline
      and also participated in telephone assessments of general cognition, verbal
      memory, and category fluency administered 5.6 years after Women's Health Study
      baseline and 2 and 4 years thereafter. Primary outcomes were standardized
      composite scores of global cognition and verbal memory. RESULTS: After adjusting
      for potential confounders, different amounts of total seafood consumption were
      not associated with changes in global cognition (p = .56) or verbal memory (p =
      .29). Considering seafood types, however, compared with women consuming less than
      once-weekly tuna or dark-meat finfish, those with once-weekly or higher
      consumption had significantly better verbal memory (0.079 standard units; p <
      .01) after 4 years-a difference comparable to that for women 2.1 years apart in
      age. There was also a statistically nonsignificant suggestion of better global
      cognition (p = .13) with once-weekly or higher tuna or dark-meat fish
      consumption. No significant associations were observed for light-meat finfish or
      shellfish. CONCLUSIONS: The relation of seafood to cognition may depend on the
      types consumed. Total consumption levels of seafood were unrelated to cognitive
      change. However, consumption of tuna and dark-meat fish once weekly or higher was
      associated with lower decline in verbal memory for a period of 4 years.

PMID- 23554465
TI  - High incidence of tuberculosis infection in rheumatic diseases and impact for
      chemoprophylactic prevention of tuberculosis activation during biologics therapy.
AB  - We conducted a long-term follow-up study in patients with rheumatic diseases who
      were candidates for biologics treatment to evaluate the effects of biologic
      agents on the risk of tuberculosis infection and the effect of prophylactic
      treatment on tuberculosis activation. One hundred one patients with rheumatic
      diseases who were candidates for biologics treatment were recruited, and 57
      healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T
      SPOT.TB test were performed for all subjects at baseline. Follow-up testing by
      the T-SPOT.TB assay was performed every 6 months in patients with rheumatic
      diseases and at 2 years of recruitment in the healthy controls. In patients with
      rheumatic diseases and healthy controls, the TST-positive (induration, >=10 mm)
      rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T
      SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P =
      0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive
      rate of 40.4%, and 49 were followed up for >=12 months with a T-SPOT.TB-positive
      rate of 36.7%, with no significant difference in the positive rate at different
      time points including baseline (P > 0.05). Long-term follow-up revealed that
      conversion to T-SPOT.TB positivity occurred only in the biologics treatment
      group, with a positive conversion rate of 11.2% (4/38). Most importantly, no
      latent tuberculosis developed into active tuberculosis during follow-up with T
      SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment
      appears to increase the risk of tuberculosis infection. However, tuberculosis
      activation could be prevented by preemptive isoniazid treatment in patients with
      latent tuberculosis infection while receiving biologics therapy.

PMID- 23554466
TI  - Sensitive and specific serodiagnosis of Leishmania infantum infection in dogs by
      using peptides selected from hypothetical proteins identified by an
      immunoproteomic approach.
AB  - In Brazil, the percentage of infected dogs living in areas where canine visceral
      leishmaniasis (CVL) is endemic ranges from 10 to 62%; however, the prevalence of
      infection in dogs is probably higher than figures reported from serological
      studies. In addition, problems with the occurrence of false-positive or false
      negative results in the serodiagnosis of CVL have been reported. The present work
      analyzed the potential of synthetic peptides mapped from hypothetical proteins
      for improvement of the serodiagnosis of Leishmania infantum infection in dogs.
      From 26 identified leishmanial proteins, eight were selected, considering that no
      homologies between these proteins and others from trypanosomatide sequence
      databases were encountered. The sequences of these proteins were mapped to
      identify linear B-cell epitopes, and 17 peptides were synthesized and tested in
      enzyme-linked immunosorbent assays (ELISAs) for the serodiagnosis of L. infantum
      infection in dogs. Of these, three exhibited sensitivity and specificity values
      higher than 75% and 90%, respectively, to differentiate L. infantum-infected
      animals from Trypanosoma cruzi-infected animals and healthy animals. Soluble
      Leishmania antigen (SLA) showed poor sensitivity (4%) and specificity (36%) to
      differentiate L. infantum-infected dogs from healthy and T. cruzi-infected dogs.
      Lastly, the three selected peptides were combined in different mixtures and
      higher sensitivity and specificity values were obtained, even when sera from T.
      cruzi-infected dogs were used. The study's findings suggest that these three
      peptides can constitute a potential tool for more sensitive and specific
      serodiagnosis of L. infantum infection in dogs.

PMID- 23554467
TI  - Disparate host immunity to Mycobacterium avium subsp. paratuberculosis antigens
      in calves inoculated with M. avium subsp. paratuberculosis, M. avium subsp.
      avium, M. kansasii, and M. bovis.
AB  - The cross-reactivity of mycobacterial antigens in immune-based diagnostic assays
      has been a major concern and a criticism of the current tests that are used for
      the detection of paratuberculosis. In the present study, Mycobacterium avium
      subsp. paratuberculosis recombinant proteins were evaluated for antigenic
      specificity compared to a whole-cell sonicate preparation (MPS). Measures of cell
      mediated immunity to M. avium subsp. paratuberculosis antigens were compared in
      calves inoculated with live M. avium subsp. paratuberculosis, M. avium subsp.
      avium (M. avium), Mycobacterium kansasii, or Mycobacterium bovis. Gamma
      interferon (IFN-gamma) responses to MPS were observed in all calves that were
      exposed to mycobacteria compared to control calves at 4 months postinfection.
      Pooled recombinant M. avium subsp. paratuberculosis proteins also elicited
      nonspecific IFN-gamma responses in inoculated calves, with the exception of
      calves infected with M. bovis. M. avium subsp. paratuberculosis proteins failed
      to elicit antigen-specific responses for the majority of immune measures;
      however, the expression of CD25 and CD26 was upregulated on CD4, CD8, gamma/delta
      (gammadelta) T, and B cells for the calves that were inoculated with either M.
      avium subsp. paratuberculosis or M. avium after antigen stimulation of the cells.
      Stimulation with MPS also resulted in the increased expression of CD26 on
      CD45RO(+) CD25(+) T cells from calves inoculated with M. avium subsp.
      paratuberculosis and M. avium. Although recombinant proteins failed to elicit
      specific responses for the calves inoculated with M. avium subsp.
      paratuberculosis, the differences in immune responses to M. avium subsp.
      paratuberculosis antigens were dependent upon mycobacterial exposure. The results
      demonstrated a close alignment in immune responses between calves inoculated with
      M. avium subsp. paratuberculosis and those inoculated with M. avium that were
      somewhat disparate from the responses in calves infected with M. bovis,
      suggesting that the biology of mycobacterial infection plays an important role in
      diagnosis.

PMID- 23554469
TI  - Phosphorylation of AMPA-type glutamate receptors: the trigger of epileptogenesis?

PMID- 23554468
TI  - Conjugation of polysaccharide 6B from Streptococcus pneumoniae with pneumococcal
      surface protein A: PspA conformation and its effect on the immune response.
AB  - Despite the substantial beneficial effects of incorporating the 7-valent
      pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype
      replacement has been observed after its widespread use. As there are many
      serotypes currently documented, the use of a conjugate vaccine relying on
      protective pneumococcal proteins as active carriers is a promising alternative to
      expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B)
      and recombinant pneumococcal surface protein A (rPspA), a well-known protective
      antigen from Streptococcus pneumoniae, were covalently attached by two
      conjugation methods. The conjugation methodology developed by our laboratory,
      employing 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT
      MM) as an activating agent through carboxamide formation, was compared with
      reductive amination, a classical methodology. DMT-MM-mediated conjugation was
      shown to be more efficient in coupling PS6B to rPspA clade 1 (rPspA1): 55.0% of
      PS6B was in the conjugate fraction, whereas 24% was observed in the conjugate
      fraction with reductive amination. The influence of the conjugation process on
      the rPspA1 structure was assessed by circular dichroism. According to our
      results, both conjugation processes reduced the alpha-helical content of rPspA;
      reduction was more pronounced when the reaction between the polysaccharide
      capsule and rPspA1 was promoted between the carboxyl groups than the amine groups
      (46% and 13%, respectively). Regarding the immune response, both conjugates
      induced functional anti-rPspA1 and anti-PS6B antibodies. These results suggest
      that the secondary structure of PspA1, as well as its reactive groups (amine or
      carboxyl) involved in the linkage to PS6B, may not play an important role in
      eliciting a protective immune response to the antigens.

PMID- 23554470
TI  - Opposing roles of corticotropin-releasing factor and neuropeptide Y within the
      dorsolateral bed nucleus of the stria terminalis in the negative affective
      component of pain in rats.
AB  - Pain is a complex experience composed of sensory and affective components.
      Although the neural systems of the sensory component of pain have been studied
      extensively, those of its affective component remain to be determined. In the
      present study, we examined the effects of corticotropin-releasing factor (CRF)
      and neuropeptide Y (NPY) injected into the dorsolateral bed nucleus of the stria
      terminalis (dlBNST) on pain-induced aversion and nociceptive behaviors in rats to
      examine the roles of these peptides in affective and sensory components of pain,
      respectively. In vivo microdialysis showed that formalin-evoked pain enhanced the
      release of CRF in this brain region. Using a conditioned place aversion (CPA)
      test, we found that intra-dlBNST injection of a CRF1 or CRF2 receptor antagonist
      suppressed pain-induced aversion. Intra-dlBNST CRF injection induced CPA even in
      the absence of pain stimulation. On the other hand, intra-dlBNST NPY injection
      suppressed pain-induced aversion. Coadministration of NPY inhibited CRF-induced
      CPA. This inhibitory effect of NPY was blocked by coadministration of a Y1 or Y5
      receptor antagonist. Furthermore, whole-cell patch-clamp electrophysiology in
      dlBNST slices revealed that CRF increased neuronal excitability specifically in
      type II dlBNST neurons, whereas NPY decreased it in these neurons. Excitatory
      effects of CRF on type II dlBNST neurons were suppressed by NPY. These results
      have uncovered some of the neuronal mechanisms underlying the affective component
      of pain by showing opposing roles of intra-dlBNST CRF and NPY in pain-induced
      aversion and opposing actions of these peptides on neuronal excitability
      converging on the same target, type II neurons, within the dlBNST.

PMID- 23554472
TI  - Human brain functional network changes associated with enhanced and impaired
      attentional task performance.
AB  - How is the cognitive performance of the human brain related to its topological
      and spatial organization as a complex network embedded in anatomical space? To
      address this question, we used nicotine replacement and duration of attentionally
      demanding task performance (time-on-task), as experimental factors expected,
      respectively, to enhance and impair cognitive function. We measured resting-state
      fMRI data, performance and brain activation on a go/no-go task demanding
      sustained attention, and subjective fatigue in n = 18 healthy, briefly abstinent,
      cigarette smokers scanned repeatedly in a placebo-controlled, crossover design.
      We tested the main effects of drug (placebo vs Nicorette gum) and time-on-task on
      behavioral performance and brain functional network metrics measured in binary
      graphs of 477 regional nodes (efficiency, measure of integrative topology;
      clustering, a measure of segregated topology; and the Euclidean physical distance
      between connected nodes, a proxy marker of wiring cost). Nicotine enhanced
      attentional task performance behaviorally and increased efficiency, decreased
      clustering, and increased connection distance of brain networks. Greater
      behavioral benefits of nicotine were correlated with stronger drug effects on
      integrative and distributed network configuration and with greater frequency of
      cigarette smoking. Greater time-on-task had opposite effects: it impaired
      attentional accuracy, decreased efficiency, increased clustering, and decreased
      connection distance of networks. These results are consistent with hypothetical
      predictions that superior cognitive performance should be supported by more
      efficient, integrated (high capacity) brain network topology at greater
      connection distance (high cost). They also demonstrate that brain network
      analysis can provide novel and theoretically principled pharmacodynamic
      biomarkers of pro-cognitive drug effects in humans.

PMID- 23554471
TI  - Hyperpolarization induces a long-term increase in the spontaneous firing rate of
      cerebellar Golgi cells.
AB  - Golgi cells (GoCs) are inhibitory interneurons that influence the cerebellar
      cortical response to sensory input by regulating the excitability of the granule
      cell layer. While GoC inhibition is essential for normal motor coordination,
      little is known about the circuit dynamics that govern the activity of these
      cells. In particular, although GoC spontaneous spiking influences the extent of
      inhibition and gain throughout the granule cell layer, it is not known whether
      this spontaneous activity can be modulated in a long-term manner. Here we
      describe a form of long-term plasticity that regulates the spontaneous firing
      rate of GoCs in the rat cerebellar cortex. We find that membrane
      hyperpolarization, either by mGluR2 activation of potassium channels, or by
      somatic current injection, induces a long-lasting increase in GoC spontaneous
      firing. This spike rate plasticity appears to result from a strong reduction in
      the spike after hyperpolarization. Pharmacological manipulations suggest the
      involvement of calcium-calmodulin-dependent kinase II and calcium-activated
      potassium channels in mediating these firing rate increases. As a consequence of
      this plasticity, GoC spontaneous spiking is selectively enhanced, but the gain of
      evoked spiking is unaffected. Hence, this plasticity is well suited for
      selectively regulating the tonic output of GoCs rather than their sensory-evoked
      responses.

PMID- 23554473
TI  - Diffusing substances during spreading depolarization: analytical expressions for
      propagation speed, triggering, and concentration time courses.
AB  - Spreading depolarization (SD) is an important phenomenon in stroke and migraine.
      However, the processes underlying the propagation of SD are still poorly
      understood, and an elementary model that is both physiological and quantitative
      is lacking. We show that, during the onset and propagation of SD, the
      concentration time courses of excitatory substances such as potassium and
      glutamate can be described with a reaction-diffusion equation. This equation
      contains four physiological parameters: (1) a concentration threshold for
      excitation; (2) a release rate; (3) a removal rate; and (4) an effective
      diffusion constant. Solving this equation yields expressions for the propagation
      velocity, concentration time courses, and the minimum stimulus that can trigger
      SD. This framework allows for analyzing experimental results in terms of these
      four parameters. The derived time courses are validated with measurements of
      potassium in rat brain tissue.

PMID- 23554474
TI  - Histone deacetylase 2 cell autonomously suppresses excitatory and enhances
      inhibitory synaptic function in CA1 pyramidal neurons.
AB  - Histone deacetylase 2 (HDAC2) negatively regulates excitatory synapse number and
      memory performance. However, whether HDAC2 regulation of excitatory synapses
      occurs in a cell-autonomous manner and whether HDAC2 regulates inhibitory
      synaptic functions are not well understood. To examine these aspects of HDAC2
      function, we used sparse transfection of rat hippocampal slice cultures and whole
      cell recordings in pyramidal neurons. HDAC2 knockdown (KD) in single postsynaptic
      pyramidal neurons enhanced, whereas HDAC2 overexpression (OE) reduced, excitatory
      synaptic transmission. Postsynaptic KD of HDAC2 also facilitated expression of
      long-term potentiation induced by subthreshold induction stimuli, without
      altering long-term depression. In contrast, HDAC2 KD reduced, whereas HDAC2 OE
      enhanced, inhibitory synaptic transmission. Alterations of postsynaptic GABA(A)
      receptors (GABA(A)Rs) likely underlie the impact of HDAC2 on inhibitory
      transmission. Consistent with this, we observed reduced transcript and protein
      levels of the GABA(A)R gamma2 subunit and reduced surface expression of the
      alpha2 subunit after HDAC2 KD. Furthermore, we observed a reduction in synaptic
      but not tonic GABA(A)R currents by HDAC2 KD, suggesting that HDAC2 selectively
      affects synaptic abundance of functional GABA(A)Rs. Immunostaining for
      postsynaptic GABA(A)Rs confirmed that HDAC2 KD and OE can regulate the synaptic
      abundance of these receptors. Together, these results highlight a role for HDAC2
      in suppressing synaptic excitation and enhancing synaptic inhibition of
      hippocampal neurons. Therefore, a shift in the balance of synaptic excitation
      versus inhibition favoring excitation could contribute to the beneficial effects
      of reducing HDAC2 function in wild-type mice or of inhibiting HDACs in models of
      cognitive impairment.

PMID- 23554475
TI  - Body posture modulates action perception.
AB  - Recent studies have highlighted cognitive and neural similarities between
      planning and perceiving actions. Given that action planning involves a simulation
      of potential action plans that depends on the actor's body posture, we reasoned
      that perceiving actions may also be influenced by one's body posture. Here, we
      test whether and how this influence occurs by measuring behavioral and cerebral
      (fMRI) responses in human participants predicting goals of observed actions,
      while manipulating postural congruency between their own body posture and
      postures of the observed agents. Behaviorally, predicting action goals is
      facilitated when the body posture of the observer matches the posture achieved by
      the observed agent at the end of his action (action's goal posture). Cerebrally,
      this perceptual postural congruency effect modulates activity in a portion of the
      left intraparietal sulcus that has previously been shown to be involved in
      updating neural representations of one's own limb posture during action planning.
      This intraparietal area showed stronger responses when the goal posture of the
      observed action did not match the current body posture of the observer. These
      results add two novel elements to the notion that perceiving actions relies on
      the same predictive mechanism as planning actions. First, the predictions
      implemented by this mechanism are based on the current physical configuration of
      the body. Second, during both action planning and action observation, these
      predictions pertain to the goal state of the action.

PMID- 23554476
TI  - Multifeatural shape processing in rats engaged in invariant visual object
      recognition.
AB  - The ability to recognize objects despite substantial variation in their
      appearance (e.g., because of position or size changes) represents such a
      formidable computational feat that it is widely assumed to be unique to primates.
      Such an assumption has restricted the investigation of its neuronal underpinnings
      to primate studies, which allow only a limited range of experimental approaches.
      In recent years, the increasingly powerful array of optical and molecular tools
      that has become available in rodents has spurred a renewed interest for rodent
      models of visual functions. However, evidence of primate-like visual object
      processing in rodents is still very limited and controversial. Here we show that
      rats are capable of an advanced recognition strategy, which relies on extracting
      the most informative object features across the variety of viewing conditions the
      animals may face. Rat visual strategy was uncovered by applying an image masking
      method that revealed the features used by the animals to discriminate two objects
      across a range of sizes, positions, in-depth, and in-plane rotations. Noticeably,
      rat recognition relied on a combination of multiple features that were mostly
      preserved across the transformations the objects underwent, and largely
      overlapped with the features that a simulated ideal observer deemed optimal to
      accomplish the discrimination task. These results indicate that rats are able to
      process and efficiently use shape information, in a way that is largely tolerant
      to variation in object appearance. This suggests that their visual system may
      serve as a powerful model to study the neuronal substrates of object recognition.

PMID- 23554477
TI  - Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse
      maturation in postnatal mouse cortex.
AB  - GABAergic basket interneurons form perisomatic synapses, which are essential for
      regulating neural networks, and their alterations are linked to various cognitive
      dysfunction. Maturation of basket synapses in postnatal cortex is activity
      dependent. In particular, activity-dependent downregulation of polysialiac acid
      carried by the neural cell adhesion molecule (NCAM) regulates the timing of their
      maturation. Whether and how NCAM per se affects GABAergic synapse development is
      unknown. Using single-cell genetics to knock out NCAM in individual basket
      interneurons in mouse cortical slice cultures, at specific developmental time
      periods, we found that NCAM loss during perisomatic synapse formation impairs the
      process of basket cell axonal branching and bouton formation. However, loss of
      NCAM once the synapses are already formed did not show any effect. We further
      show that NCAM120 and NCAM140, but not the NCAM180 isoform, rescue the phenotype.
      Finally, we demonstrate that a dominant-negative form of Fyn kinase mimics,
      whereas a constitutively active form of Fyn kinase rescues, the effects of NCAM
      knockdown. Altogether, our data suggest that NCAM120/NCAM140-mediated Fyn
      activation promotes GABAergic synapse maturation in postnatal cortex.

PMID- 23554478
TI  - Proliferation and cell cycle dynamics in the developing stellate ganglion.
AB  - Cell proliferation during nervous system development is poorly understood outside
      the mouse neocortex. We measured cell cycle dynamics in the embryonic mouse
      sympathetic stellate ganglion, where neuroblasts continue to proliferate
      following neuronal differentiation. At embryonic day (E) 9.5, when neural crest
      derived cells were migrating and coalescing into the ganglion primordium, all
      cells were cycling, cell cycle length was only 10.6 h, and S-phase comprised over
      65% of the cell cycle; these values are similar to those previously reported for
      embryonic stem cells. At E10.5, Sox10(+) cells lengthened their cell cycle to 38
      h and reduced the length of S-phase. As cells started to express the neuronal
      markers Tuj1 and tyrosine hydroxylase (TH) at E10.5, they exited the cell cycle.
      At E11.5, when >80% of cells in the ganglion were Tuj1(+)/TH(+) neuroblasts, all
      cells were again cycling. Neuroblast cell cycle length did not change
      significantly after E11.5, and 98% of Sox10(-)/TH(+) cells had exited the cell
      cycle by E18.5. The cell cycle length of Sox10(+)/TH(-) cells increased during
      late embryonic development, and ~25% were still cycling at E18.5. Loss of Ret
      increased neuroblast cell cycle length at E16.5 and decreased the number of
      neuroblasts at E18.5. A mathematical model generated from our data successfully
      predicted the relative change in proportions of neuroblasts and non-neuroblasts
      in wild-type mice. Our results show that, like other neurons, sympathetic neuron
      differentiation is associated with exit from the cell cycle; sympathetic neurons
      are unusual in that they then re-enter the cell cycle before later permanently
      exiting.

PMID- 23554480
TI  - HIV-1 Tat C modulates expression of miRNA-101 to suppress VE-cadherin in human
      brain microvascular endothelial cells.
AB  - HIV-1 infection leads to the development of HIV-associated neurological
      disorders. The HIV-1 Tat protein has been reported to exert an adverse effect on
      blood-brain barrier integrity and permeability. Perturbation in permeability is
      mainly caused by disruptions in adherens junctions and tight junction proteins.
      We have identified HIV-1 Tat C-induced disruption of VE-cadherin mediated by
      miRNA-101 in human brain microvascular endothelial cells (BMVECs). HIV-1 Tat C
      increased the expression of miR-101, which led to downregulation of VE-cadherin.
      Overexpression of miR-101 resulted into the suppression of VE-cadherin.
      Inhibition of miR-101 by the miRNA inhibitor enhanced the expression of VE
      cadherin. We have demonstrated that VE-cadherin is a direct target of miR-101
      using a luciferase reporter assay, which showed that mutated VE-cadherin 3'UTR
      and miR-101 cotransfection did not change luciferase activity. By overexpression
      and knockdown of miR-101, we have demonstrated that the expression level of
      claudin-5 is governed by the expression of VE-cadherin. These findings
      demonstrate a novel mechanism for the regulation of barrier permeability by miR
      101 via posttranscriptional regulation of VE-cadherin in human BMVECs exposed to
      the HIV-1 Tat C protein.

PMID- 23554479
TI  - Oligodendrocyte-specific activation of PERK signaling protects mice against
      experimental autoimmune encephalomyelitis.
AB  - There is compelling evidence that oligodendrocyte apoptosis, in response to CNS
      inflammation, contributes significantly to the development of the demyelinating
      disorder multiple sclerosis and its animal model, experimental autoimmune
      encephalomyelitis (EAE). Therefore, approaches designed to protect
      oligodendrocytes would likely have therapeutic value. Activation of pancreatic
      endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic
      reticulum (ER) stress increases cell survival under various cytotoxic conditions.
      Moreover, there is evidence that PERK signaling is activated in oligodendrocytes
      within demyelinating lesions in multiple sclerosis and EAE. Our previous study
      demonstrated that CNS delivery of the inflammatory cytokine interferon-gamma
      before EAE onset protected mice against EAE, and this protection was dependent on
      PERK signaling. In our current study, we sought to elucidate the role of PERK
      signaling in oligodendrocytes during EAE. We generated transgenic mice that allow
      for temporally controlled activation of PERK signaling, in the absence of ER
      stress, specifically in oligodendrocytes. We demonstrated that persistent
      activation of PERK signaling was not deleterious to oligodendrocyte viability or
      the myelin of adult animals. Importantly, we found that enhanced activation of
      PERK signaling specifically in oligodendrocytes significantly attenuated EAE
      disease severity, which was associated with reduced oligodendrocyte apoptosis,
      demyelination, and axonal degeneration. This effect was not the result of an
      altered degree of the inflammatory response in EAE mice. Our results provide
      direct evidence that activation of PERK signaling in oligodendrocytes is
      cytoprotective, protecting mice against EAE.

PMID- 23554481
TI  - Toward high performance, weakly invasive brain computer interfaces using
      selective visual attention.
AB  - Brain-computer interfaces have been proposed as a solution for paralyzed persons
      to communicate and interact with their environment. However, the neural signals
      used for controlling such prostheses are often noisy and unreliable, resulting in
      a low performance of real-world applications. Here we propose neural signatures
      of selective visual attention in epidural recordings as a fast, reliable, and
      high-performance control signal for brain prostheses. We recorded epidural field
      potentials with chronically implanted electrode arrays from two macaque monkeys
      engaged in a shape-tracking task. For single trials, we classified the direction
      of attention to one of two visual stimuli based on spectral amplitude, coherence,
      and phase difference in time windows fixed relative to stimulus onset.
      Classification performances reached up to 99.9%, and the information about
      attentional states could be transferred at rates exceeding 580 bits/min. Good
      classification can already be achieved in time windows as short as 200 ms. The
      classification performance changed dynamically over the trial and modulated with
      the task's varying demands for attention. For all three signal features, the
      information about the direction of attention was contained in the gamma-band. The
      most informative feature was spectral amplitude. Together, these findings
      establish a novel paradigm for constructing brain prostheses as, for example,
      virtual spelling boards, promising a major gain in performance and robustness for
      human brain-computer interfaces.

PMID- 23554482
TI  - Maladaptive bias for extrahippocampal navigation strategies in aging humans.
AB  - Efficient spatial navigation requires not only accurate spatial knowledge but
      also the selection of appropriate strategies. Using a novel paradigm that allowed
      us to distinguish between beacon, associative cue, and place strategies, we
      investigated the effects of cognitive aging on the selection and adoption of
      navigation strategies in humans. Participants were required to rejoin a
      previously learned route encountered from an unfamiliar direction. Successful
      performance required the use of an allocentric place strategy, which was
      increasingly observed in young participants over six experimental sessions. In
      contrast, older participants, who were able to recall the route when approaching
      intersections from the same direction as during encoding, failed to use the
      correct place strategy when approaching intersections from novel directions.
      Instead, they continuously used a beacon strategy and showed no evidence of
      changing their behavior across the six sessions. Given that this bias was already
      apparent in the first experimental session, the inability to adopt the correct
      place strategy is not related to an inability to switch from a firmly established
      response strategy to an allocentric place strategy. Rather, and in line with
      previous research, age-related deficits in allocentric processing result in
      shifts in preferred navigation strategies and an overall bias for response
      strategies. The specific preference for a beacon strategy is discussed in the
      context of a possible dissociation between beacon-based and associative-cue-based
      response learning in the striatum, with the latter being more sensitive to age
      related changes.

PMID- 23554483
TI  - Modulation of alpha power and functional connectivity during facial affect
      recognition.
AB  - Research has linked oscillatory activity in the alpha frequency range,
      particularly in sensorimotor cortex, to processing of social actions. Results
      further suggest involvement of sensorimotor alpha in the processing of facial
      expressions, including affect. The sensorimotor face area may be critical for
      perception of emotional face expression, but the role it plays is unclear. The
      present study sought to clarify how oscillatory brain activity contributes to or
      reflects processing of facial affect during changes in facial expression.
      Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed
      videos of human faces that changed their expression from neutral to fearful,
      neutral, or happy expressions. Induced changes in alpha power during the
      different morphs, source analysis, and graph-theoretic metrics served to identify
      the role of alpha power modulation and cross-regional coupling by means of phase
      synchrony during facial affect recognition. Changes from neutral to emotional
      faces were associated with a 10-15 Hz power increase localized in bilateral
      sensorimotor areas, together with occipital power decrease, preceding reported
      emotional expression recognition. Graph-theoretic analysis revealed that, in the
      course of a trial, the balance between sensorimotor power increase and decrease
      was associated with decreased and increased transregional connectedness as
      measured by node degree. Results suggest that modulations in alpha power
      facilitate early registration, with sensorimotor cortex including the
      sensorimotor face area largely functionally decoupled and thereby protected from
      additional, disruptive input and that subsequent alpha power decrease together
      with increased connectedness of sensorimotor areas facilitates successful facial
      affect recognition.

PMID- 23554484
TI  - Entorhinal stellate cells show preferred spike phase-locking to theta inputs that
      is enhanced by correlations in synaptic activity.
AB  - In active networks, excitatory and inhibitory synaptic inputs generate membrane
      voltage fluctuations that drive spike activity in a probabilistic manner. Despite
      this, some cells in vivo show a strong propensity to precisely lock to the local
      field potential and maintain a specific spike-phase relationship relative to
      other cells. In recordings from rat medial entorhinal cortical stellate cells, we
      measured spike phase-locking in response to sinusoidal "test" inputs in the
      presence of different forms of background membrane voltage fluctuations,
      generated via dynamic clamp. We find that stellate cells show strong and robust
      spike phase-locking to theta (4-12 Hz) inputs. This response occurs under a wide
      variety of background membrane voltage fluctuation conditions that include a
      substantial increase in overall membrane conductance. Furthermore, the IH current
      present in stellate cells is critical to the enhanced spike phase-locking
      response at theta. Finally, we show that correlations between inhibitory and
      excitatory conductance fluctuations, which can arise through feedback and
      feedforward inhibition, can substantially enhance the spike phase-locking
      response. The enhancement in locking is a result of a selective reduction in the
      size of low-frequency membrane voltage fluctuations due to cancellation of
      inhibitory and excitatory current fluctuations with correlations. Hence, our
      results demonstrate that stellate cells have a strong preference for spike phase
      locking to theta band inputs and that the absolute magnitude of locking to theta
      can be modulated by the properties of background membrane voltage fluctuations.

PMID- 23554486
TI  - High-mobility group box-1 protein and beta-amyloid oligomers promote neuronal
      differentiation of adult hippocampal neural progenitors via receptor for advanced
      glycation end products/nuclear factor-kappaB axis: relevance for Alzheimer's
      disease.
AB  - Dysregulated hippocampal neurogenesis has been associated with neurodegenerative
      disorders, including Alzheimer's disease (AD), in which it may potentially
      represent an auto-reparatory mechanism that could counteract neuronal loss and
      cognitive impairment. We evaluated hippocampal neurogenesis in TgCRND8 mice and
      reported that, at 32 weeks of age, corresponding to an advanced AD-like
      neuropathology stage, increased numbers of proliferating cells, doublecortin
      expressing progenitors/neuroblasts, and early postmitotic calretinin-expressing
      neurons were present compared with wild-type (WT) littermates. When hippocampal
      neural progenitor cells (NPCs) were isolated from TgCRND8 mice, we demonstrated
      that (1) their neurogenic potential was higher compared with WT NPCs; (2) medium
      conditioned by TgCRND8 NPC promoted neuronal differentiation of WT NPCs; and (3)
      the proneurogenic effect of TgCRND8-conditioned medium was counteracted by
      blockade of the receptor for advanced glycation end products (RAGE)/nuclear
      factor-kappaB (NF-kappaB) axis. Furthermore, we showed that beta-amyloid 1-42
      (Abeta(1-42)) oligomers, but not monomers and fibrils, and the alarmin high
      mobility group box-1 protein (HMGB-1) could promote neuronal differentiation of
      NPCs via activation of the RAGE/NF-kappaB axis. Altogether, these data suggest
      that, in AD brain, an endogenous proneurogenic response could be potentially
      triggered and involve signals (Abeta(1-42) oligomers and HMGB-1) and pathways
      (RAGE/NF-kappaB activation) that also contribute to
      neuroinflammation/neurotoxicity. A more detailed analysis confirmed no
      significant increase of new mature neurons in hippocampi of TgCRND8 compared with
      WT mice, suggesting reduced survival and/or integration of newborn neurons.
      Therapeutic strategies in AD should ideally combine the ability of sustaining
      hippocampal neurogenesis as well as of counteracting an hostile brain
      microenvironment so to promote survival of vulnerable cell populations, including
      adult generated neurons.

PMID- 23554487
TI  - Millisecond stimulus onset-asynchrony enhances information about components in an
      odor mixture.
AB  - Airborne odorants rarely occur as pure, isolated stimuli. In a natural
      environment, odorants that intermingle from multiple sources create mixtures in
      which the onset and offset of odor components are asynchronous. Odor mixtures are
      known to elicit interactions in both behavioral and physiological responses,
      changing the perceptive quality of mixtures compared with the components.
      However, relevant odors need to be segregated from a distractive background.
      Honeybees (Apis mellifera) can use stimulus onset asynchrony of as little as 6 ms
      to segregate learned odor components within a mixture. Using in vivo calcium
      imaging of projection neurons in the honeybee, we studied neuronal mechanisms of
      odor-background segregation based on stimulus onset asynchrony in the antennal
      lobe. We found that asynchronous mixtures elicit response patterns that are
      different from their synchronous counterpart: the responses to asynchronous
      mixtures contain more information about the constituent components. With longer
      onset shifts, more features of the components were present in the mixture
      response patterns. Moreover, we found that the processing of asynchronous
      mixtures activated more inhibitory interactions than the processing of
      synchronous mixtures. This study provides evidence of neuronal mechanisms that
      underlie odor-object segregation on a timescale much faster than found for
      mammals.

PMID- 23554485
TI  - Triple cysteine module within M-type K+ channels mediates reciprocal channel
      modulation by nitric oxide and reactive oxygen species.
AB  - We have identified a new signaling role for nitric oxide (NO) in neurons from the
      trigeminal ganglia (TG). We show that in rat sensory neurons from the TG the NO
      donor, S-nitroso-N-acetyl-dl-penicillamine, inhibited M-current. This inhibitory
      effect was blocked by NO scavenging, while inhibition of NO synthases increased M
      current, suggesting that tonic NO levels inhibit M-current in TG neurons.
      Moreover NO increased neuronal excitability and calcitonin gene-related peptide
      (CGRP) release and these effects could be prevented by perturbing M-channel
      function. First, NO-induced depolarization was prevented by pre-application of
      the M-channel blocker XE991 and second, NO-induced increase in CGRP release was
      prevented by incubation with the M-channel opener retigabine. We investigated the
      mechanism of the effects of NO on M-channels and identified a site of action of
      NO to be the redox modulatory site at the triplet of cysteines within the
      cytosolic linker between transmembrane domains 2 and 3, which is also a site of
      oxidative modification of M-channels by reactive oxygen species (ROS). NO and
      oxidative modifications have opposing effects on M-current, suggesting that a
      tightly controlled local redox and NO environment will exert fine control over M
      channel activity and thus neuronal excitability. Together our data have
      identified a dynamic redox sensor within neuronal M-channels, which mediates
      reciprocal regulation of channel activity by NO and ROS. This sensor may play an
      important role in mediating excitatory effects of NO in such trigeminal disorders
      as headache and migraine.

PMID- 23554488
TI  - Experience-dependent modulation of feedback integration during singing: role of
      the right anterior insula.
AB  - Somatosensation plays an important role in the motor control of vocal functions,
      yet its neural correlate and relation to vocal learning is not well understood.
      We used fMRI in 17 trained singers and 12 nonsingers to study the effects of
      vocal-fold anesthesia on the vocal-motor singing network as a function of singing
      expertise. Tasks required participants to sing musical target intervals under
      normal conditions and after anesthesia. At the behavioral level, anesthesia
      altered pitch accuracy in both groups, but singers were less affected than
      nonsingers, indicating an experience-dependent effect of the intervention. At the
      neural level, this difference was accompanied by distinct patterns of decreased
      activation in singers (cortical and subcortical sensory and motor areas) and
      nonsingers (subcortical motor areas only) respectively, suggesting that
      anesthesia affected the higher-level voluntary (explicit) motor and sensorimotor
      integration network more in experienced singers, and the lower-level (implicit)
      subcortical motor loops in nonsingers. The right anterior insular cortex (AIC)
      was identified as the principal area dissociating the effect of expertise as a
      function of anesthesia by three separate sources of evidence. First, it responded
      differently to anesthesia in singers (decreased activation) and nonsingers
      (increased activation). Second, functional connectivity between AIC and bilateral
      A1, M1, and S1 was reduced in singers but augmented in nonsingers. Third,
      increased BOLD activity in right AIC in singers was correlated with larger pitch
      deviation under anesthesia. We conclude that the right AIC and sensory-motor
      areas play a role in experience-dependent modulation of feedback integration for
      vocal motor control during singing.

PMID- 23554489
TI  - Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic
      spines and progressive synaptic and behavioral abnormalities.
AB  - Despite evidence for a strong genetic contribution to several major psychiatric
      disorders, individual candidate genes account for only a small fraction of these
      disorders, leading to the suggestion that multigenetic pathways may be involved.
      Several known genetic risk factors for psychiatric disease are related to the
      regulation of actin polymerization, which plays a key role in synaptic
      plasticity. To gain insight into and test the possible pathogenetic role of this
      pathway, we designed a conditional knock-out of the Arp2/3 complex, a conserved
      final output for actin signaling pathways that orchestrates de novo actin
      polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in
      forebrain excitatory neurons leads to an asymmetric structural plasticity of
      dendritic spines, followed by a progressive loss of spine synapses. This
      progression of synaptic deficits corresponds with an evolution of distinct
      cognitive, psychomotor, and social disturbances as the mice age. Together, these
      results point to the dysfunction of actin signaling, specifically that which
      converges to regulate Arp2/3, as an important cellular pathway that may
      contribute to the etiology of complex psychiatric disorders.

PMID- 23554490
TI  - Itch and analgesia resulting from intrathecal application of morphine:
      contrasting effects on different populations of trigeminothalamic tract neurons.
AB  - Intrathecal application of morphine is among the most powerful methods used to
      treat severe chronic pain. However, this approach commonly produces itch
      sufficiently severe that patients are forced to choose between relief of pain or
      itch. The neuronal populations responsible for processing and transmitting
      information underlying itch caused by intrathecal application of morphine have
      not been identified and characterized. We describe two populations of
      antidromically identified trigeminothalamic tract (VTT) neurons in anesthetized
      rats that are differentially affected by morphine and explain several aspects of
      opioid-induced itch and analgesia. We found that intrathecal application of
      morphine increased ongoing activity of itch-responsive VTT neurons. In addition,
      intrathecal application of morphine increased responses to pruritogens injected
      into the skin and greatly heightened responses to innocuous mechanical stimuli.
      In contrast, the ongoing activity and responses to noxious pinches in nociceptive
      VTT neurons were frequently inhibited by the same dose of morphine. These results
      reveal that i.t. application of morphine affects specific subpopulations of VTT
      neurons in ways that may produce itch, hyperknesis, alloknesis, and analgesia.

PMID- 23554491
TI  - A neuronal GPCR is critical for the induction of the heat shock response in the
      nematode C. elegans.
AB  - In the nematode Caenorhabditis elegans, the heat shock response (HSR) is
      regulated at the organismal level by a network of thermosensory neurons that
      senses elevated temperatures and activates the HSR in remote tissues. Which
      neuronal receptors are required for this signaling mechanism and in which neurons
      they function are largely unanswered questions. Here we used worms that were
      engineered to exhibit RNA interference hypersensitivity in neurons to screen for
      neuronal receptors that are required for the activation of the HSR and identified
      a putative G-protein coupled receptor (GPCR) as a novel key component of this
      mechanism. This gene, which we termed GPCR thermal receptor 1 (gtr-1), is
      expressed in chemosensory neurons and has no role in heat sensing but is
      critically required for the induction of genes that encode heat shock proteins in
      non-neural tissues upon exposure to heat. Surprisingly, the knock-down of gtr-1
      by RNA interference protected worms expressing the Alzheimer's-disease-linked
      aggregative peptide Abeta3-42 from proteotoxicity but had no effect on lifespan.
      This study provides several novel insights: (1) it shows that chemosensory
      neurons play important roles in the nematode's HSR-regulating mechanism, (2) it
      shows that lifespan and heat stress resistance are separable, and (3) it
      strengthens the emerging notion that the ability to respond to heat comes at the
      expense of protein homeostasis (proteostasis).

PMID- 23554492
TI  - BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic
      branching.
AB  - Dendritic arborization of neurons is regulated by brain-derived neurotrophic
      factor (BDNF) together with its receptor, TrkB. Endocytosis is required for
      dendritic branching and regulates TrkB signaling, but how postendocytic
      trafficking determines the neuronal response to BDNF is not well understood. The
      monomeric GTPase Rab11 regulates the dynamics of recycling endosomes and local
      delivery of receptors to specific dendritic compartments. We investigated whether
      Rab11-dependent trafficking of TrkB in dendrites regulates BDNF-induced dendritic
      branching in rat hippocampal neurons. We report that TrkB in dendrites is a cargo
      for Rab11 endosomes and that both Rab11 and its effector, MyoVb, are required for
      BDNF/TrkB-induced dendritic branching. In addition, BDNF induces the accumulation
      of Rab11-positive endosomes and GTP-bound Rab11 in dendrites and the expression
      of a constitutively active mutant of Rab11 is sufficient to increase dendritic
      branching by increasing TrkB localization in dendrites and enhancing
      sensitization to endogenous BDNF. We propose that Rab11-dependent dendritic
      recycling provides a mechanism to retain TrkB in dendrites and to increase local
      signaling to regulate arborization.

PMID- 23554493
TI  - Sucrose ingestion induces rapid AMPA receptor trafficking.
AB  - The mechanisms by which natural rewards such as sugar affect synaptic
      transmission and behavior are largely unexplored. Here, we investigate regulation
      of nucleus accumbens synapses by sucrose intake. Previous studies have shown that
      AMPA receptor (AMPAR) trafficking is a major mechanism for regulating synaptic
      strength, and that in vitro, trafficking of AMPARs containing the GluA1 subunit
      takes place by a two-step mechanism involving extrasynaptic and then synaptic
      receptor transport. We report that in rat, repeated daily ingestion of a 25%
      sucrose solution transiently elevated spontaneous locomotion and potentiated
      accumbens core synapses through incorporation of Ca(2+)-permeable AMPA receptors
      (CPARs), which are GluA1-containing, GluA2-lacking AMPARs. Electrophysiological,
      biochemical, and quantitative electron microscopy studies revealed that sucrose
      training (7 d) induced a stable (>24 h) intraspinous GluA1 population, and that
      in these rats a single sucrose stimulus rapidly (5 min) but transiently (<24 h)
      elevated GluA1 at extrasynaptic sites. CPARs and dopamine D1 receptors were
      required in vivo for elevated locomotion after sucrose ingestion. Significantly,
      a 7 d protocol of daily ingestion of a 3% solution of saccharin, a noncaloric
      sweetener, induced synaptic GluA1 similarly to 25% sucrose ingestion. These
      findings identify multistep GluA1 trafficking, previously described in vitro, as
      a mechanism for acute regulation of synaptic transmission in vivo by a natural
      orosensory reward. Trafficking is stimulated by a chemosensory pathway that is
      not dependent on the caloric value of sucrose.

PMID- 23554494
TI  - Abstract representations of location and facing direction in the human brain.
AB  - Humans, like other mobile organisms, rely on spatial representations to guide
      navigation from place to place. Although previous work has identified neural
      systems involved in wayfinding, the specific spatial codes supported by these
      systems are not well understood. We use functional magnetic resonance imaging to
      identify regions within the human medial temporal and medial parietal lobes that
      encode two fundamental spatial quantities-location and facing direction-in a
      manner that abstracts away from sensory inputs. University students were scanned
      while viewing photographs taken at several familiar campus locations. Multivoxel
      pattern analyses indicated that the left presubiculum, retrosplenial complex, and
      parietal-occipital sulcus coded location identity even across non-overlapping
      views, whereas the right presubiculum coded facing direction even across
      noncontiguous locations. The location and direction codes supported by these
      regions may be critical to our ability to navigate within the extended
      environment and to understand its large-scale spatial structure.

PMID- 23554496
TI  - Ambient temperature affects the temperature threshold for TRPM8 activation
      through interaction of phosphatidylinositol 4,5-bisphosphate.
AB  - Cold sensation is an important and fundamental sense for animals and it is known
      to be affected by ambient temperature. Transient Receptor Potential Melastatin 8
      (TRPM8), a nonselective cation channel expressed in a subset of peripheral
      afferent fibers, acts as a cold sensor, having an activation threshold of ~28
      degrees C. Although the cold temperature threshold of TRPM8 is affected by
      menthol or pH, ambient temperature has not been reported to affect it. Because
      the cold temperature threshold was thought to be unchanged by alterations in
      ambient temperature, the relativity of temperature sensing in different ambient
      temperatures could not be understood at the level of molecular function of
      thermosensitive TRP channels. Here, we show that ambient temperature changed the
      temperature threshold for activation of human and rat TRPM8 in a heterologous
      expression system and cold responses in mouse DRG neurons. Moreover, reducing the
      level of cellular phosphatidylinositol 4,5-bisphosphate (PIP2) attenuated changes
      in the cold temperature threshold after alterations in ambient temperature. A
      single amino acid mutation at position 1008 in the C terminus of TRPM8 (arginine
      to glutamine) also attenuated changes in the cold temperature threshold induced
      by ambient temperature. These findings suggest that ambient temperature does
      affect the temperature threshold for TRPM8 activation through interaction of
      PIP2.

PMID- 23554495
TI  - The p38alpha MAPK regulates microglial responsiveness to diffuse traumatic brain
      injury.
AB  - Neuropathology after traumatic brain injury (TBI) is the result of both the
      immediate impact injury and secondary injury mechanisms. Unresolved post
      traumatic glial activation is a secondary injury mechanism that contributes to a
      chronic state of neuroinflammation in both animal models of TBI and human head
      injury patients. We recently demonstrated, using in vitro models, that p38alpha
      MAPK signaling in microglia is a key event in promoting cytokine production in
      response to diverse disease-relevant stressors and subsequent inflammatory
      neuronal dysfunction. From these findings, we hypothesized that the p38alpha
      signaling pathway in microglia could be contributing to the secondary
      neuropathologic sequelae after a diffuse TBI. Mice where microglia were p38alpha
      deficient (p38alpha KO) were protected against TBI-induced motor deficits and
      synaptic protein loss. In wild-type (WT) mice, diffuse TBI produced microglia
      morphological activation that lasted for at least 7 d; however, p38alpha KO mice
      failed to activate this response. Unexpectedly, we found that the peak of the
      early, acute phase cytokine and chemokine levels was increased in injured
      p38alpha KO mice compared with injured WT mice. The increased cytokine levels in
      the p38alpha KO mice could not be accounted for by more infiltration of
      macrophages or neutrophils, or increased astrogliosis. By 7 d after injury, the
      cytokine and chemokine levels remained elevated in injured WT mice but not in
      p38alpha KO mice. Together, these data suggest that p38alpha balances the
      inflammatory response by acutely attenuating the early proinflammatory cytokine
      surge while perpetuating the chronic microglia activation after TBI.

PMID- 23554497
TI  - Effort and valuation in the brain: the effects of anticipation and execution.
AB  - Neural representations of the effort deployed in performing actions, and the
      valence of the outcomes they yield, form the foundation of action choice. To
      discover whether brain areas represent effort and outcome valence together or if
      they represent one but not the other, we examined these variables in an
      explicitly orthogonal way. We did this by asking human subjects to exert one of
      two levels of effort to improve their chances of either winning or avoiding the
      loss of money. Subjects responded faster both when exerting greater effort and
      when exerting effort in anticipation of winning money. Using fMRI, we inspected
      BOLD responses during anticipation (before any action was executed) and when the
      outcome was delivered. In this way, we indexed BOLD signals associated with an
      anticipated need to exert effort and its affective consequences, as well as the
      effect of executed effort on the representation of outcomes. Anterior cingulate
      cortex and dorsal striatum (dorsal putamen) signaled the anticipation of effort
      independently of the prospect of winning or losing. Activity in ventral striatum
      (ventral putamen) was greater for better-than-expected outcomes compared with
      worse-than-expected outcomes, an effect attenuated in the context of having
      exerted greater effort. Our findings provide evidence that neural representations
      of anticipated actions are sensitive to the expected demands, but not to the
      expected value of their consequence, whereas representations of outcome value are
      discounted by exertion, commensurate with an integration of cost and benefit so
      as to approximate net value.

PMID- 23554498
TI  - Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance
      regulating centers of the postnatal and adult hypothalamus.
AB  - Increasing evidence suggests that neurogenesis occurs in the postnatal and adult
      mammalian hypothalamus. However, the identity and location of the putative
      progenitor cells is under much debate, and little is known about the dynamics of
      neurogenesis in unchallenged brain. Previously, we postulated that Fibroblast
      growth factor 10-expressing (Fgf10(+)) tanycytes constitute a population of
      progenitor cells in the mouse hypothalamus. Here, we show that Fgf10(+) tanycytes
      express markers of neural stem/progenitor cells, divide late into postnatal life,
      and can generate both neurons and astrocytes in vivo. Stage-specific lineage
      tracing of Fgf10(+) tanycytes using Fgf10-creERT2 mice, reveals robust
      neurogenesis at postnatal day 28 (P28), lasting as late as P60. Furthermore, we
      present evidence for amplification of Fgf10-lineage traced neural cells within
      the hypothalamic parenchyma itself. The neuronal descendants of Fgf10(+)
      tanycytes predominantly populate the arcuate nucleus, a subset of which express
      the orexigenic neuronal marker, Neuropeptide-Y, and respond to fasting and leptin
      induced signaling. These studies provide direct evidence in support of
      hypothalamic neurogenesis during late postnatal and adult life, and identify
      Fgf10(+) tanycytes as a source of parenchymal neurons with putative roles in
      appetite and energy balance.

PMID- 23554500
TI  - Na+ channel-dependent recruitment of Navbeta4 to axon initial segments and nodes
      of Ranvier.
AB  - The axon initial segment (AIS) and nodes of Ranvier are the sites of action
      potential initiation and regeneration in axons. Although the basic molecular
      architectures of AIS and nodes, characterized by dense clusters of Na(+) and K(+)
      channels, are similar, firing patterns vary among cell types. Neuronal firing
      patterns are established by the collective activity of voltage-gated ion channels
      and can be modulated through interaction with auxiliary subunits. Here, we report
      the neuronal expression pattern and subcellular localization of Navbeta4, the
      modulatory Na(+) channel subunit thought to underlie resurgent Na(+) current.
      Immunostaining of rat tissues revealed that Navbeta4 is strongly enriched at the
      AIS of a select set of neuron types, including many characterized by high
      frequency firing, and at nodes of Ranvier in the PNS and some nodes in the CNS.
      By introducing full-length and mutant GFP-tagged Navbeta4 into cultured neurons,
      we determined that the AIS and nodal localization of Navbeta4 depends on its
      direct interaction with Na(+) channel alpha subunits through an extracellular
      disulfide bond. Based on these results, we propose that differences in the
      specific composition of the Na(+) channel complexes enriched at the AIS and nodes
      contribute to the diverse physiologies observed among cell types.

PMID- 23554499
TI  - An activated protein C analog stimulates neuronal production by human neural
      progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway.
AB  - Activated protein C (APC) is a protease with anticoagulant and cell-signaling
      activities. In the CNS, APC and its analogs with reduced anticoagulant activity
      but preserved cell signaling activities, such as 3K3A-APC, exert neuroprotective,
      vasculoprotective, and anti-inflammatory effects. Murine APC promotes
      subependymal neurogenesis in rodents in vivo after ischemic and traumatic brain
      injury. Whether human APC can influence neuronal production from resident
      progenitor cells in humans is unknown. Here we show that 3K3A-APC, but not S360A
      APC (an enzymatically inactive analog of APC), stimulates neuronal mitogenesis
      and differentiation from fetal human neural stem and progenitor cells (NPCs). The
      effects of 3K3A-APC on proliferation and differentiation were comparable to those
      obtained with fibroblast growth factor and brain-derived growth factor,
      respectively. Its promoting effect on neuronal differentiation was accompanied by
      inhibition of astroglial differentiation. In addition, 3K3A-APC exerted modest
      anti-apoptotic effects during neuronal production. These effects appeared to be
      mediated through specific protease activated receptors (PARs) and sphingosine-1
      phosphate receptors (S1PRs), in that siRNA-mediated inhibition of PARs 1-4 and
      S1PRs 1-5 revealed that PAR1, PAR3, and S1PR1 are required for the neurogenic
      effects of 3K3A-APC. 3K3A-APC activated Akt, a downstream target of S1PR1, which
      was inhibited by S1PR1, PAR1, and PAR3 silencing. Adenoviral transduction of NPCs
      with a kinase-defective Akt mutant abolished the effects of 3K3A-APC on NPCs,
      confirming a key role of Akt activation in 3K3A-APC-mediated neurogenesis.
      Therefore, APC and its pharmacological analogs, by influencing PAR and S1PR
      signals in resident neural progenitor cells, may be potent modulators of both
      development and repair in the human CNS.

PMID- 23554501
TI  - PPARalpha regulates cholinergic-driven activity of midbrain dopamine neurons via
      a novel mechanism involving alpha7 nicotinic acetylcholine receptors.
AB  - Ventral tegmental area dopamine neurons control reward-driven learning, and their
      dysregulation can lead to psychiatric disorders. Tonic and phasic activity of
      these dopaminergic neurons depends on cholinergic tone and activation of
      nicotinic acetylcholine receptors (nAChRs), particularly those containing the
      beta2 subunit (beta2*-nAChRs). Nuclear peroxisome proliferator-activated
      receptors type-alpha (PPARalpha) tonically regulate beta2*-nAChRs and thereby
      control dopamine neuron firing activity. However, it is unknown how and when
      PPARalpha endogenous ligands are synthesized by dopamine cells. Using ex vivo and
      in vivo electrophysiological techniques combined with biochemical and behavioral
      analysis, we show that activation of alpha7-nAChRs increases in the rat VTA both
      the tyrosine phosphorylation of the beta2 subunit of nAChRs and the levels of two
      PPARalpha endogenous ligands in a Ca(2+)-dependent manner. Accordingly, in vivo
      production of endogenous PPARalpha ligands, triggered by alpha7-nAChR activation,
      blocks in rats nicotine-induced increased firing activity of dopamine neurons and
      displays antidepressant-like properties. These data demonstrate that endogenous
      PPARalpha ligands are effectors of alpha7-nAChRs and that their neuromodulatory
      properties depend on phosphorylation of beta2*-nAChRs on VTA dopamine cells. This
      reveals an autoinhibitory mechanism aimed at reducing dopamine cell
      overexcitation engaged during hypercholinergic drive. Our results unveil
      important physiological functions of nAChR/PPARalpha signaling in dopamine
      neurons and how behavioral output can change after modifications of this
      signaling pathway. Overall, the present study suggests PPARalpha as new
      therapeutic targets for disorders associated with unbalanced dopamine
      acetylcholine systems.

PMID- 23554502
TI  - Dissociation between dorsal and ventral hippocampal theta oscillations during
      decision-making.
AB  - Hippocampal theta oscillations are postulated to support mnemonic processes in
      humans and rodents. Theta oscillations facilitate encoding and spatial
      navigation, but to date, it has been difficult to dissociate the effects of
      volitional movement from the cognitive demands of a task. Therefore, we examined
      whether volitional movement or cognitive demands exerted a greater modulating
      factor over theta oscillations during decision-making. Given the anatomical,
      electrophysiological, and functional dissociations along the dorsal-ventral axis,
      theta oscillations were simultaneously recorded in the dorsal and ventral
      hippocampus in rats trained to switch between place and motor-response
      strategies. Stark differences in theta characteristics were found between the
      dorsal and ventral hippocampus in frequency, power, and coherence. Theta power
      increased in the dorsal, but decreased in the ventral hippocampus, during the
      decision-making epoch. Interestingly, the relationship between running speed and
      theta power was uncoupled during the decision-making epoch, a phenomenon limited
      to the dorsal hippocampus. Theta frequency increased in both the dorsal and
      ventral hippocampus during the decision epoch, although this effect was greater
      in the dorsal hippocampus. Despite these differences, ventral hippocampal theta
      was responsive to the navigation task; theta frequency, power, and coherence were
      all affected by cognitive demands. Theta coherence increased within the dorsal
      hippocampus during the decision-making epoch on all three tasks. However,
      coherence selectively increased throughout the hippocampus (dorsal to ventral) on
      the task with new hippocampal learning. Interestingly, most results were
      consistent across tasks, regardless of hippocampal-dependent learning. These data
      indicate increased integration and cooperation throughout the hippocampus during
      information processing.

PMID- 23554503
TI  - Anatomical segregation of visual selection mechanisms in human parietal cortex.
AB  - Visual selection requires mechanisms for representing object salience and for
      shifting the focus of processing to novel objects. It is not clear from
      computational or neural models whether these operations are performed within the
      same or different brain regions. Here, we use repetitive transcranial magnetic
      stimulation to briefly interfere with neural activity in individually localized
      regions of human posterior parietal cortex (PPC) that are putatively involved in
      attending to contralateral locations or shifting attention between locations.
      Stimulation over right ventral intraparietal sulcus impaired target
      discrimination at contralateral locations, whereas stimulation over right medial
      superior parietal lobule impaired target discrimination after a shift of
      attention regardless of its location. This double dissociation is consistent with
      neuroimaging studies and indicates that mechanisms of visual selection are partly
      anatomically segregated in human PPC.

PMID- 23554505
TI  - Planar scintigraphy with 123I/99mTc-sestamibi, 99mTc-sestamibi SPECT/CT, 11C
      methionine PET/CT, or selective venous sampling before reoperation of primary
      hyperparathyroidism?
AB  - All patients with primary hyperparathyroidism should undergo localization studies
      before reoperation, but it is not known which method is most accurate. The
      purpose of this prospective study was to compare the performance of planar
      scintigraphy with (123)I/(99m)Tc-sestamibi, (99m)Tc-sestamibi SPECT (SPECT/CT),
      (11)C-methionine PET/CT, and selective venous sampling (SVS) in persistent
      primary hyperparathyroidism. METHODS: Twenty-one patients referred for
      reoperation of persistent hyperparathyroidism were included and investigated with
      (123)I/(99m)Tc-sestamibi, SPECT/CT (n = 19), (11)C-methionine PET/CT, and SVS (n
      = 18) before reoperation. All patients had been operated on 1-2 times previously
      because of hyperparathyroidism. The results of the localization studies were
      compared with operative findings, histology, and biochemical cure. RESULTS:
      Eighteen (86%) of 21 patients were biochemically cured. Nineteen parathyroid
      glands (9 adenomas, 1 atypical adenoma, and 9 hyperplastic glands) were removed
      from 17 patients, and 1 patient who was biochemically cured had an unclear
      histology result. The accuracy for localizing a pathologic parathyroid gland to
      the correct side of the neck was 59% (95% confidence interval [CI], 36%-79%) for
      (123)I/(99m)Tc-sestamibi, 19% (95% CI, 5%-42%) for SPECT/CT, 65% (95% CI, 43%
      84%) for (11)C-methionine PET/CT, and 40% (95% CI, 19%-65%) for SVS (P < 0.01 for
      (123)I/(99m)Tc-sestamibi vs. SPECT/CT). The corresponding accuracy for the
      correct quadrant or more specific site was 48% (95% CI, 27%-69%) for
      (123)I/(99m)Tc-sestamibi, 14% (95% CI, 3%-36%) for SPECT/CT, 61% (95% CI, 39%
      80%) for (11)C-methionine PET/CT, and 25% (95% CI, 9%-49%) for SVS (P < 0.02 for
      (123)I/(99m)Tc-sestamibi vs. SPECT/CT). In the 3 patients not cured, preoperative
      (123)I/(99m)Tc-sestamibi and SPECT/CT remained negative, SVS was false predictive
      in all, and (11)C-methionine PET/CT in 1. (11)C-methionine PET/CT accurately
      revealed the pathologic gland in 4 of 8 (50%) patients with a negative
      (123)I/(99m)Tc-sestamibi scan result, all of whom were biochemically cured after
      reoperation. CONCLUSION: Planar scintigraphy with (123)I/(99m)Tc-sestamibi
      performs well in complicated primary hyperparathyroidism and is recommended as
      first-line imaging before reoperation. (11)C-methionine PET/CT provides valuable
      additional information if (123)I/(99m)Tc-sestamibi scan results remain negative.
      (99m)Tc-sestamibi SPECT/CT and SVS provide no additional information, compared
      with the combined results of (123)I/(99m)Tc-sestamibi and (11)C-methionine PET/CT
      imaging.

PMID- 23554504
TI  - Functional characterization of the extraclassical receptive field in macaque V1:
      contrast, orientation, and temporal dynamics.
AB  - Neurons in primary visual cortex, V1, very often have extraclassical receptive
      fields (eCRFs). The eCRF is defined as the region of visual space where stimuli
      cannot elicit a spiking response but can modulate the response of a stimulus in
      the classical receptive field (CRF). We investigated the dependence of the eCRF
      on stimulus contrast and orientation in macaque V1 cells for which the laminar
      location was determined. The eCRF was more sensitive to contrast than the CRF
      across the whole population of V1 cells with the greatest contrast differential
      in layer 2/3. We confirmed that many V1 cells experience stronger suppression for
      collinear than orthogonal stimuli in the eCRF. Laminar analysis revealed that the
      predominant bias for collinear suppression was found in layers 2/3 and 4b. The
      laminar pattern of contrast and orientation dependence suggests that eCRF
      suppression may derive from different neural circuits in different layers, and
      may be comprised of two distinct components: orientation-tuned and untuned
      suppression. On average tuned suppression was delayed by ~25 ms compared with the
      onset of untuned suppression. Therefore, response modulation by the eCRF develops
      dynamically and rapidly in time.

PMID- 23554506
TI  - First experience of 18F-alfatide in lung cancer patients using a new lyophilized
      kit for rapid radiofluorination.
AB  - (18)F-FPPRGD2, which was approved for clinical study recently, has favorable
      properties for integrin targeting and showed potential for antiangiogenic therapy
      and early response monitoring. However, the time-consuming multiple-step
      synthesis may limit its widespread applications in the clinic. In this study, we
      developed a simple lyophilized kit for labeling PRGD2 peptide ((18)F-AlF-NOTA
      PRGD2, denoted as (18)F-alfatide) using a fluoride-aluminum complex that
      significantly simplified the labeling procedure. METHODS: Nine patients with a
      primary diagnosis of lung cancer were examined by both static and dynamic PET
      imaging with (18)F-alfatide, and 1 tuberculosis patient was investigated using
      both (18)F-alfatide and (18)F-FDG imaging. Standardized uptake values were
      measured in tumors and other main organs at 30 min and 1 h after injection.
      Kinetic parameters were calculated by Logan graphical analysis.
      Immunohistochemistry and staining intensity quantification were performed to
      confirm the expression of integrin alpha(v)beta(3). RESULTS: Under the optimal
      conditions, the whole radiosynthesis including purification was accomplished
      within 20 min with a decay-corrected yield of 42.1% +/- 2.0% and radiochemical
      purity of more than 95%. (18)F-alfatide PET imaging identified all tumors, with
      mean standardized uptake values of 2.90 +/- 0.10. Tumor-to-muscle and tumor-to
      blood ratios were 5.87 +/- 2.02 and 2.71 +/- 0.92, respectively. CONCLUSION:
      (18)F-alfatide can be produced with excellent radiochemical yield and purity via
      a simple, 1-step, lyophilized kit. PET scanning with (18)F-alfatide allows
      specific imaging of alphavbeta3 expression with good contrast in lung cancer
      patients. This technique might be used for the assessment of angiogenesis and for
      planning and response evaluation of cancer therapies that would affect
      angiogenesis status and integrin expression levels.

PMID- 23554508
TI  - Medical cost and frequent mental distress among the non-elderly US adult
      population.
AB  - BACKGROUND: Frequent mental distress (FMD) is an important measure of perceived
      poor mental health. With the rising cost of health care, it is not uncommon for
      working adults to delay seeking care. The objective of this study was to
      determine the relationship between avoidance of medical care due to cost and FMD
      among the non-elderly US population. METHODS: We analyzed data from 282 044 non
      elderly US population from a 2008 Behavioral Risk Factor Surveillance System
      survey. Multivariable logistic regression models were used to assess the
      association between avoidance of medical care due to cost and FMD adjusted for
      covariates. RESULTS: The overall prevalence of FMD in the non-elderly population
      was 11.1%; whereas it was 24.2% for those reporting avoiding medical care due to
      cost. Approximately 18% of the population had no health insurance coverage and
      the prevalence of FMD was significantly greater in this group. The odds of FMD
      were >2-fold elevated for respondents who were unable to see a doctor because of
      cost (adjusted odds ratio: 2.40, 99% confidence interval: 2.19, 2.63).
      CONCLUSIONS: These findings highlight the need for affordable medical care for
      reducing mental distress and improving population health.

PMID- 23554507
TI  - Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs.
AB  - Renal expression of the peptide hormone urotensin II (UII) and its receptor (UTR)
      are dependent on kidney maturation and anatomical regions. However, renal
      regional hemodynamic effects of UII in neonates are unclear. Here, we
      investigated regional hemodynamic responses to acute intrarenal arterial
      administration of UII in newborn pigs. Western immunoblotting and
      immunofluorescence confirmed UTR expression and membrane localization in newborn
      pig renal afferent arterioles and afferent arteriolar smooth muscle cells
      respectively. Intrarenal arterial bolus injections of human UII (hUII; 1-100 
      ng/kg) resulted in a dose-dependent decrease in total renal blood flow (RBF) and
      an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR)
      in newborn pigs. Moreover, hUII dose dependently reduced cortical blood flow
      (CBF) but increased medullary blood flow (MBF) in the piglets. hUII-induced MAP
      elevation and hemodynamic changes were inhibited by urantide, a UTR antagonist,
      but not losartan, a type 1 angiotensin II receptor antagonist. U-73122, a
      phospholipase C (PLC) inhibitor, and 2-aminoethoxydiphenyl borate, an inositol
      1,4,5 trisphosphate (IP3) receptor antagonist, attenuated hUII-induced MAP and
      RVR elevations, RBF and CBF reductions, but not MBF increase. These findings
      indicate that intrarenal arterial administration of hUII elevates blood pressure
      and induces region-selective renal hemodynamic changes in newborn pigs. Our data
      also suggest that the PLC/IP3 signaling pathway contributes to hUII-induced
      alterations in MAP, RBF, RVR, and CBF but not MBF in newborn pigs.

PMID- 23554509
TI  - Smoking-related disease risk, area deprivation and health behaviours.
AB  - BACKGROUND: Smokers and ex-smokers are at risk of many chronic diseases. However,
      never smokers and never smokers exposed to environmental tobacco smoke (ETS) are
      also at risk. Additionally, smoking behaviours and their associated disease risk
      are socially patterned and positively associated with health inequalities.
      However, other lifestyle choices also contribute to health inequalities. We aim
      to assess the contribution of other lifestyle behaviours pertaining to alcohol,
      physical inactivity and weight to smoking-related disease risk across (i) the
      socioeconomic spectrum and (ii) smoking status. METHODS: Smoking-related disease
      risk is modelled using probit analysis. The results are used to predict disease
      risk across the socioeconomic dimension and smoking status for a set of healthy
      and unhealthy behaviours using the administratively linked Scottish Health
      Surveys and Scottish Morbidity Records. RESULTS: The results confirm the
      deprivation gradient in disease risk regardless of smoking status group.
      Imposition of healthy (unhealthy) lifestyle behaviours decreases (increases) the
      predicted risk across the deprivation distribution regardless of smoking status
      providing evidence of the multifaceted health behavioural determinants of disease
      risk across the deprivation distribution. CONCLUSION: The results are of policy
      interest as they suggest that to reduce inequalities in smoking-related diseases,
      interventions reducing both smoking and other unhealthy behaviours are required.

PMID- 23554510
TI  - Measuring current and future cost of skin cancer in England.
AB  - BACKGROUND: Increasing incidence of and mortality from skin cancer are posing a
      large financial burden on the NHS in England. Information provided by cost-of
      illness (CoI) studies are used in policy making and are particularly useful for
      measuring the potential savings from averting a case of disease. METHODS: We
      estimate the cost of skin cancer in England, and model future costs up to 2020.
      We compare two costing approaches (top-down and bottom-up). RESULTS: We estimate
      that costs due to skin cancer were in the range of L106-L112 million in 2008.
      These figures are very closely related to those provided by the Department of
      Health (estimated to be L104.0 million in 2007-8 and L105.2 million 2008-9). The
      expected cost per case of malignant melanoma was estimated to be L2607 and L2560,
      using the bottom-up and top-down approaches, respectively. The mean cost per case
      of non-melanoma skin cancer was L889 and L1226, respectively. We estimate that
      the cost to the NHS due to skin cancer will amount to over L180 million in 2020.
      CONCLUSION: Effective prevention of skin cancer might not only reduce a
      significant burden of disease but it could also save considerable resources to
      the NHS.

PMID- 23554511
TI  - Is roll-your-own tobacco substitute for manufactured cigarettes: evidence from
      Ireland?
AB  - BACKGROUND: When tax policies increase tobacco prices some smokers may switch to
      smoking cheaper roll-your-own (RYO) tobacco. To reduce the harm from smoking,
      this substitution effect should be avoided. This study analyses whether RYO
      tobacco is a substitute for manufactured cigarettes (MCs) in Ireland, a country
      with relatively high price for both products. METHODS: Data on duty-paid
      consumption of RYO tobacco from 1978 to 2011 are used to estimate the demand by
      applying seemingly unrelated regression and error correction models. Covariates
      include prices of tobacco in Ireland and in the UK, income and a variable
      describing tobacco-related health policies. RESULTS: We failed to find evidence
      of RYO tobacco being a substitute for MC due to price differences. However, an
      increase in incomes (1%) is associated with a reduction in the consumption of RYO
      tobacco (-0.4%), which can be due to substitution towards MCs in addition to
      quitting or cutting back. Also, an increase in the price of RYO tobacco (1%) is
      associated with a reduction in its consumption (-1%). CONCLUSIONS: Increasing
      prices via taxation is an effective way of reducing the consumption of RYO
      tobacco but due to associations between RYO tobacco smoking and lower incomes,
      these policies should be accompanied by measures aimed at helping smokers to
      quit.

PMID- 23554512
TI  - Community-acquired, non-occupational needlestick injuries treated in US Emergency
      Departments.
AB  - BACKGROUND: The escalating number of persons self-injecting medications,
      predominantly insulin, has generated concerns that the public is at risk of
      acquiring blood-borne infections from discarded needles/syringes. Communities
      have developed disposal guidelines but a debate continues over the need for
      further legislation and/or at-home safety devices. This study examines the
      number, characteristics, treatment and costs of community-acquired needlestick
      injuries (CANSIs). METHODS: US-representative CANSI rates and characteristics
      were derived from 2001-08 National Electronic Injury Surveillance System All
      Injury Program data on product-related injuries treated at US emergency
      departments (EDs). CANSI-related medical care was examined using 2003-09 National
      Hospital Ambulatory Medical Care Surveys, representing all US ED visits. Cost
      analyses used 2010 Current Procedural Terminology Coding and Medicare rates.
      RESULTS: In 2001-08, an estimated 16 677 CANSIs were treated in US EDs, with an
      associated annual rate of 0.7 per 100 000 US citizens (95% CI 0.6-0.8) and no
      observable temporal trend. The estimated maximum annual medical cost of ED
      treated CANSIs was $9.8 million, or $0.03 per citizen, $1.66 per insulin
      injecting person and $0.0018 per insulin injection. CONCLUSIONS: US ED-treated
      CANSI rates are extremely low. Stricter disposal programs and the at-home use of
      safety devices do not appear to be needed at this time.

PMID- 23554513
TI  - Statistical foundations of liquid-crystal theory: II: Macroscopic balance laws.
AB  - Working on a state space determined by considering a discrete system of rigid
      rods, we use nonequilibrium statistical mechanics to derive macroscopic balance
      laws for liquid crystals. A probability function that satisfies the Liouville
      equation serves as the starting point for deriving each macroscopic balance. The
      terms appearing in the derived balances are interpreted as expected values and
      explicit formulas for these terms are obtained. Among the list of derived
      balances appear two, the tensor moment of inertia balance and the mesofluctuation
      balance, that are not standard in previously proposed macroscopic theories for
      liquid crystals but which have precedents in other theories for structured media.

PMID- 23554514
TI  - Ultrafast E to Z photoisomerization dynamics of the Cph1 phytochrome.
AB  - Femtosecond photodynamics of the reverse ( 15E Pfr-> 15Z Pr) reaction of the
      red/far-red phytochrome Cph1 from Synechocystis were resolved with visible
      broadband transient absorption spectroscopy. Multi-phasic dynamics were resolved
      and separated via global target analysis into a fast-decaying (260 fs) excited
      state population that bifurcates to generate the isomerized Lumi-F primary
      photoproduct and a non-isomerizing vibrationally excited ground state that
      relaxes back into the 15E Pfr ground state on a 2.8-ps time scale. Relaxation on
      a 1-ms timescale results in the loss of red absorbing region, but not blue
      region, of Lumi-F, which indicates that formation of 15Z Pr occurs on slower
      timescales.

PMID- 23554516
TI  - Scaling up opioid dependence treatment in low- and middle-income settings.

PMID- 23554517
TI  - Opioid substitution: improving cost-efficiency.

PMID- 23554519
TI  - Opioid treatment in Ukraine risks losing momentum.
AB  - Ukraine has made progress in introducing opioid substitution therapy since 2004,
      but the coverage of these services remains inadequate while injecting drug use
      continues to drive the country's HIV epidemic. Gary Humphreys reports.

PMID- 23554520
TI  - New treatment gives hope to East Africa's drug users.
AB  - The United Republic of Tanzania is the first mainland sub-Saharan country to
      launch a national methadone programme as part of its battle to fight the twin
      epidemics of heroin addiction and HIV infection. Fumbuka Ng'wanakilala reports.

PMID- 23554521
TI  - Drug control and public health: getting beyond stalemate. Interview with Robin
      Room by Fiona Fleck.
AB  - Robin Room is a member of a drugs policy modelling group that uses data to
      project what would happen to the harm caused by illicit drugs if policies or
      conditions changed. He talks to Fiona Fleck about alternative scenarios to
      today's illicit trade in drugs and the implications of different scenarios for
      public health.

PMID- 23554522
TI  - Methadone maintenance treatment and mortality in HIV-positive people who inject
      opioids in China.
AB  - OBJECTIVE: To examine the effect of methadone maintenance treatment (MMT) on
      mortality in people injecting opioids who receive antiretroviral therapy (ART)
      for the treatment of human immunodeficiency virus (HIV) infection in China.
      METHODS: The study involved a nationwide cohort of 23 813 HIV-positive (HIV+)
      people injecting opioids who received ART between 31 December 2002 and 31
      December 2011. Mortality rates and demographic, disease and treatment
      characteristics were compared in patients who received either ART and MMT or ART
      only. Factors associated with mortality were identified by univariate and
      multivariate analysis. FINDINGS: Overall, 3057 deaths occurred during 41 959
      person-years of follow-up (mortality: 7.3 per 100 person-years; 95% confidence
      interval, CI: 7.0-7.5). Mortality 6 months after starting ART was significantly
      lower with ART and MMT than with ART only (6.6 versus 16.9 per 100 person-years,
      respectively; P < 0.001). After 12 months, mortality was 3.7 and 7.4 per 100
      person-years in the two groups, respectively (P < 0.001). Not having received MMT
      was an independent predictor of death (adjusted hazard ratio: 1.4; 95% CI: 1.3
      1.6). Other predictors were a low haemoglobin level and a low CD4+ T-lymphocyte
      count at ART initiation and treatment at facilities other than infectious disease
      hospitals. CONCLUSION: Patients would benefit more from both MMT and HIV
      treatment programmes and would face fewer barriers to care if cross-referrals
      between programmes were promoted and ART and MMT services were located together.

PMID- 23554523
TI  - Mortality among people who inject drugs: a systematic review and meta-analysis.
AB  - OBJECTIVE: To systematically review cohort studies of mortality among people who
      inject drugs, examine mortality rates and causes of death in this group, and
      identify participant- and study-level variables associated with a higher risk of
      death. METHODS: Tailored search strings were used to search EMBASE, Medline and
      PsycINFO. The grey literature was identified through online grey literature
      databases. Experts were consulted to obtain additional studies and data. Random
      effects meta-analyses were performed to estimate pooled crude mortality rates
      (CMRs) and standardized mortality ratios (SMRs). FINDINGS: Sixty-seven cohorts of
      people who inject drugs were identified, 14 of them from low- and middle-income
      countries. The pooled CMR was 2.35 deaths per 100 person-years (95% confidence
      interval, CI: 2.12-2.58). SMRs were reported for 32 cohorts; the pooled SMR was
      14.68 (95% CI: 13.01-16.35). Comparison of CMRs and the calculation of CMR ratios
      revealed mortality to be higher in low- and middle-income country cohorts, males
      and people who injected drugs that were positive for human immunodeficiency virus
      (HIV). It was also higher during off-treatment periods. Drug overdose and
      acquired immunodeficiency syndrome (AIDS) were the primary causes of death across
      cohorts. CONCLUSION: Compared with the general population, people who inject
      drugs have an elevated risk of death, although mortality rates vary across
      different settings. Any comprehensive approach to improving health outcomes in
      this group must include efforts to reduce HIV infection as well as other causes
      of death, particularly drug overdose.

PMID- 23554524
TI  - Implementing methadone maintenance treatment in prisons in Malaysia.
AB  - PROBLEM: In Malaysia, human immunodeficiency virus (HIV) infection is highly
      concentrated among people who inject opioids. For this reason, the country
      undertook a three-phase roll-out of a methadone maintenance treatment (MMT)
      programme. In Phase 3, described in this paper, MMT was implemented within
      prisons and retention in care was assessed. APPROACH: After developing standard
      operating procedures and agreement between its Prisons Department and Ministry of
      Health, Malaysia established pilot MMT programmes in two prisons in the states of
      Kelantan (2008) and Selangor (2009) - those with the highest proportions of HIV
      infected prisoners. Community-based MMT programmes were also established in
      Malaysia to integrate treatment activities after prisoners' release. LOCAL
      SETTING: Having failed to reduce the incidence of HIV infection, in 2005 Malaysia
      embarked on a harm reduction strategy. RELEVANT CHANGES: STANDARD OPERATING
      PROCEDURES WERE MODIFIED TO: (i) escalate the dose of methadone more slowly; (ii)
      provide ongoing education and training for medical and correctional staff and
      inmates; (iii) increase the duration of methadone treatment before releasing
      prisoners; (iv) reinforce linkages with community MMT programmes after prisoners'
      release; (v) screen for and treat tuberculosis; (vi) escalate the dose of
      methadone during treatment for HIV infection and tuberculosis; and (vii) optimize
      the daily oral dose of methadone (> 80 mg) before releasing prisoners. LESSONS
      LEARNT: Prison-based MMT programmes can be effectively implemented but require
      adequate dosing and measures are needed to improve communication between prison
      and police authorities, prevent police harassment of MMT clients after their
      release, and improve systems for tracking release dates.

PMID- 23554525
TI  - Human resource development and capacity-building during China's rapid scale-up of
      methadone maintenance treatment services.
AB  - PROBLEM: China's National Methadone Maintenance Treatment Programme (MMT) has
      expanded from eight clinics serving approximately 1000 clients to 738 clinics
      that have served more than 340 000 clients cumulatively in only 8 years. This has
      created an enormous demand for trained providers. APPROACH: Human resource
      development and capacity building efforts have been conducted in China's National
      MMT Programme to create a supply of providers trained in administering MMT for
      opioid dependence. LOCAL SETTING: From 2004 to 2007, China's National MMT
      Programme faced several problems: inappropriately low methadone doses, poor
      compliance, high concurrent drug use and high drop-out rates among clients, and
      little experience, little training and high turnover rates among providers.
      RELEVANT CHANGES: Training programmes for individual providers and their trainers
      were redeveloped and expanded in 2008. Although programme performance metrics
      show an increase in patients' annual mean duration in treatment (93 days in 2004
      versus 238 days in 2011), the increase in their mean daily methadone dose (from
      47.2 mg in 2004 to 58.6 mg in 2011) is modest. LESSONS LEARNT: Some of the
      problems that can arise during the development, launch and scale-up of a major
      national public health effort, such as China's National MMT Programme, cannot be
      foreseen. Key to the programme's success so far have been the strong commitment
      on the part of China's government and the optimism and pragmatism of programme
      managers. Human resources development and capacity-building during scale-up have
      contributed to improved service quality in MMT treatment clinics and are critical
      to long-term success.

PMID- 23554526
TI  - Methadone maintenance treatment in Spain: the success of a harm reduction
      approach.
AB  - PROBLEM: During the 1980s, Spain had very strict laws limiting access to opioid
      agonist maintenance treatment (OAMT). Because of this, mortality among people who
      used illicit opioids and other illicit drugs was high. Spain was also the
      European country with the highest number of cases of acquired immunodeficiency
      syndrome transmitted through illicit drug injection. APPROACH: The rapid spread
      of human immunodeficiency virus (HIV) infection among people using heroin led to
      a shift from a drug-free approach to the treatment of opioid dependence to one
      focused on harm reduction. A substantial change in legislation made it possible
      to meet public health needs and offer OAMT as part of harm reduction programmes
      in the public health system, including prisons. LOCAL SETTING: Legislative
      changes were made throughout the country, although at a different pace in
      different regions. RELEVANT CHANGES: Legal changes facilitated the expansion of
      OAMT, which has achieved a coverage of 60%. A parallel reduction in the annual
      incidence of HIV infection has been reported. Reductions in morbidity and
      mortality and improved health-related quality of life have been described in
      patients undergoing OAMT. LESSONS LEARNT: The treatment of opioid dependence has
      been more heavily influenced by moral concepts and prejudices that hinder
      legislation and interfere with the implementation of OAMT than by scientific
      evidence. To fulfil public health needs, OAMT should be integrated in harm
      reduction programmes offered primarily in public facilities, including prisons.
      Longitudinal studies are needed to detect unmet needs and evaluate programme
      impact and suitability.

PMID- 23554527
TI  - Arguments in favour of compulsory treatment of opioid dependence.
AB  - Twelve agencies of the United Nations, including the World Health Organization,
      have issued a joint statement that calls on Member States to replace the
      compulsory detention of people who use opioids in treatment centres with
      voluntary, evidence-informed and rights-based health and social services. The
      arguments in favour of this position fall into three broad categories: Compulsory
      treatment centres infringe on an individual's liberty, they put human beings at
      risk of harm, and evidence of their effectiveness against opioid dependence has
      not been generated. The United Nations statement underscores that although
      countries apply different criteria for sending individuals to compulsory
      treatment centres, detention often takes place without due process, legal
      safeguards or judicial review. This clearly violates internationally recognized
      human rights standards. Furthermore, people who are committed to these centres
      are often exposed to physical and sexual violence, forced labour and sub-standard
      living conditions. They are often denied health care, despite their heightened
      vulnerability to HIV infection and tuberculosis. Finally, there is no evidence,
      according to the statement, that these centres offer an environment that is
      conducive to recovery from opioid dependence or to the rehabilitation of
      commercial sex workers or of children who have suffered sexual exploitation,
      abuse or lack of care and protection. The author of this paper sets forth several
      arguments that counter the position taken by the United Nations and argues in
      favour of compulsory treatment within a broader harm reduction strategy aimed at
      protecting society as well as the individual concerned.

PMID- 23554528
TI  - Advocates need to show compulsory treatment of opioid dependence is effective,
      safe and ethical.

PMID- 23554529
TI  - Voluntary treatment, not detention, in the management of opioid dependence.

PMID- 23554530
TI  - Mitigating the risk of HIV infection with opioid substitution treatment.

PMID- 23554531
TI  - Delivery models of opioid agonist maintenance treatment in South Asia: a good
      beginning.

PMID- 23554532
TI  - Managing tuberculosis in people who use and inject illicit drugs.

PMID- 23554534
TI  - Effect of shunting of collateral flow into the venous system on arteriogenesis
      and angiogenesis in rabbit hind limb.
AB  - The aim of this study was to characterize the vascular remodeling in the external
      iliac artery (EIA) and the lower leg muscles in a rabbit shunt model created
      between the distal stump of the occluded femoral artery and the accompanying
      vein. Histology and immunoconfocal microscopy were used in this study. We found
      that: 1) both endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (P
      eNOS) proteins were significantly increased in the shunt-side EIA; 2) matrix
      metalloproteinase-2 (MMP-2) expression was 5.5 times in shunt side EIA over that
      in normal EIA; 3) intercellular adhension molecule-1 (ICAM-1) expression was
      strongly induced in endothelial cells (EC) and vascular adhension molecule-1
      (VCAM-1) expression was significantly increased in both EC and the adventitia of
      the shunt-side EIA; 4) augmentation of cell proliferation and extracellular
      proteolysis by macrophage infiltration was observed in shunt-side EIA; 5) cell
      proliferation was active in shunt side EIA, but quiet in shunt side lower leg's
      arterial vessels; 6) capillary density in shunt side lower leg muscles was 2
      times over that in normal side. In conclusion, our data demonstrate the paradigm
      that the power of shear stress takes the reins in arteriogenesis, whereas
      ischemia in angiogenesis, but not in arteriogenesis.

PMID- 23554535
TI  - Expression of Glutamate and GABA during the Process of Rat Retinal Synaptic
      Plasticity Induced by Acute High Intraocular Pressure.
AB  - Acute high intraocular pressure (HIOP) can induce plastic changes of retinal
      synapses during which the expression of the presynaptic marker synaptophysin
      (SYN) has a distinct spatiotemporal pattern from the inner plexiform layer to the
      outer plexiform layer. We identified the types of neurotransmitters in the retina
      that participated in this process and determined the response of these
      neurotransmitters to HIOP induction. The model of acute HIOP was established by
      injecting normal saline into the anterior chamber of the rat eye. We found that
      the number of glutamate-positive cells increased successively from the inner part
      to the outer part of the retina (from the ganglion cell layer to the inner
      nuclear layer to the outer nuclear layer) after HIOP, which was similar to the
      spatiotemporal pattern of SYN expression (internally to externally) following
      HIOP. However, the distribution and intensity of GABA immunoreactivity in the
      retina did not change significantly at different survival time post injury and
      had no direct correlation with SYN expression. Our results suggested that the
      excitatory neurotransmitter glutamate might participate in the plastic process of
      retinal synapses following acute HIOP, but no evidence was found for the role of
      the inhibitory neurotransmitter GABA.

PMID- 23554536
TI  - Efficient Genetic Analysis of Microdissected Samples by Agarose-Bead Method:
      Alterations of beta-Catenin Gene in Fundic Gland Polyp and Heterotopic Gastric
      Mucosa of Duodenum.
AB  - Molecular genetic analyses of archival formalin-fixed, paraffin-embedded (FFPE)
      pathological specimens taken at biopsy or autopsy, are occasionally compromised
      because the DNA molecules therein are inevitably degraded. Furthermore, since
      these tissue samples comprise various cell types, the analyses based on mixtures
      of such heterogeneous populations often fail to reflect the nature of the
      affected cells. In the present study, to elucidate the contribution of beta
      catenin gene mutation to the fundic gland polyp and the heterotopic gastric
      mucosa in the duodenum, we successfully introduced an agarose-bead mediated
      technique as an effectual tool for retrospective morphology-oriented genetic
      analyses. Microdissected samples were embedded in low-melting agarose, and
      directly treated with proteinase K. A fragment of the agarose-bead was used as a
      template for polymerase chain reaction to analyze beta-catenin mutation. Of the
      six cases of heterotopic gastric mucosa in the duodenum associated with fundic
      gland polyps, one showed a common 1-bp missense mutation at codon 37 shared by
      both the fundic gland polyp and the heterotopic gastric mucosa. Alternatively, a
      1-bp silent mutation at codon 33 and missense mutation at codon 32 were
      identified only in the heterotopic gastric mucosa. Agarose-bead mediated
      technique shows superior sensitivity to the previously described techniques and
      is an effectual tool for retrospective morphology-oriented genetic analyses using
      a large number of archival pathological samples stored for long periods in the
      pathology laboratory.

PMID- 23554537
TI  - Induction of beta-Defensin Expression by Porphyromonas gingivalis-Infected Human
      Gingival Graft Transplanted in nu/nu Mouse Subdermis.
AB  - It is important to understand the onset of periodontal disease in terms of
      bacterial infection and host factors. Host-bacteria interactions can be elicited
      in human cultured cells and animal models, but these models provide only limited
      biological information about human host reactions against bacterial attacks.
      Development of an in vivo model using human gingival tissue is needed. We
      established an in vivo model using nu/nu mice and evaluated host defense
      following bacterial infection in human gingiva. Human gingival samples were
      collected from periodontitis patients and transplanted in nu/nu mouse subdermis.
      After 2 weeks, human characteristics were confirmed by positive
      immunohistochemical reactions for human-specific markers. We used this model to
      investigate human beta-defensin-2 (hBD-2), an antimicrobial peptide that
      contributes to initial defense against bacterial invasion. Using real-time
      polymerase chain reaction, in situ hybridization, and immunohistochemistry, we
      investigated whether hBD-2 expression was induced in human gingiva as a response
      to Porphyromonas gingivalis as a periodontal pathogen. Two hours after infection
      with bacteria, we detected increased expression of hBD-2 mRNA, which was
      localized in the epithelium of human gingiva. Using our in vivo model, we
      concluded that increased hBD-2 may play an important role in early defense from
      bacterial infection in human gingival epithelium.

PMID- 23554538
TI  - Expression of Toll-Like Receptor 4 in Glomerular Endothelial Cells under Diabetic
      Conditions.
AB  - Diabetic conditions promote glomerulosclerosis by mesangial cells but the
      mechanisms are not fully elucidated. The present study evaluated the expression
      of toll-like receptor 4 in glomerular endothelial cells in the streptozotocin
      (STZ)-induced type 1 diabetic mouse (ICR-STZ) and the type 2 diabetic KK/TaJcl
      mouse which were fed a high fat diet feed (KK/Ta-HF). In the ICR-STZ and KK/Ta-HF
      almost glomeruli were immunostained with anti-TLR4 but there was no glomerulus
      immunostained by ani-TLR4 in the control ICR and KK/Ta. Laser-scanning confocal
      microscopy showed that the TLR4-positive region did not coincide with the
      podoplanin-positive region but coincide with the PECAM-1- and VE-cadherin
      positive regions in the glomeruli of the ICR-STZ and KK/Ta-HF. The in situ
      hybridization showed that almost signals for TLR4 mRNA were present in the
      glomerulus of the ICR-STZ and KK/Ta-HF to a stronger extent than in the control
      ICR and KK/Ta. These suggest that glomerular endothelial cells usually express
      the TLR4 gene and hyperglycemia in the diabetic condition induces the TLR4
      protein expression in the glomerular capillary endothelial cells. Cytokine
      productions through the TLR signaling pathway in glomerular endothelial cells may
      allow mesangial cells to produce extracellular matrix proteins in the diabetic
      milieu.

PMID- 23554539
TI  - Changes in expression of connexin 32, bile canaliculus-like structures, and
      localization of alkaline phosphatase in primary cultures of fetal rat
      hepatocytes.
AB  - We devised an experimental design in primary cultures of fetal rat hepatocytes
      for studying hepatocyte differentiation over a short period. In the present
      study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented
      medium and then for an additional 3 days in dexamethasone- or epidermal growth
      factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone
      supplemented medium, the expression of connexin 32 increased and bile canaliculus
      like structures and localization of alkaline phosphatase in the plasma membrane
      around bile canaliculus-like structures were maintained. Few cells incorporated
      bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in
      epidermal growth factor-supplemented medium, the expression of connexin 32 was
      minimally recognized, bile canaliculus-like structures were shortened or
      eliminated, and alkaline phosphatase was localized as numerous fine spots
      throughout the cytoplasm. More than 20% of all hepatocytes incorporated
      bromodeoxyuridine. The present study suggests that in hepatocytes, there is a
      close relationship among connexin 32 expression, the maintenance of bile
      canaliculus-like structures, and the localization of alkaline phosphatase to the
      plasma membrane around the bile canaliculus-like structures, and this indicates
      that the present experimental model is useful for studying hepatocyte
      differentiation over a short period.

PMID- 23554540
TI  - In Situ Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the
      Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones.
AB  - Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and
      prorenin, was studied in rat pituitary gland. In situ hybridization showed that
      cells expressing (P)RR mRNA were widely distributed in the anterior lobe and
      intermediate lobe of the pituitary gland. Double-staining using in situ
      hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones
      showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in
      the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH
      cells, but not in LH cells. The present study has shown for the first time the
      distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These
      findings suggest that (P)RR plays physiological roles in the pituitary gland,
      such as the modulation of the pituitary hormone secretion.

PMID- 23554541
TI  - Intimate Partner Violence in Interracial and Monoracial Couples.
AB  - This study investigated intimate partner violence in interracial and monoracial
      relationships. Using a nationally representative sample, regression analyses
      indicated that interracial couples demonstrated a higher level of mutual IPV than
      monoracial white couples but a level similar to monoracial black couples. There
      were significant gender differences in IPV, with women reporting lower levels of
      victimization than men. Regarding relationship status, cohabiting couples
      demonstrated the highest levels of IPV and dating couples reported the lowest
      levels. Regarding interactions among couple racial composition, relationship
      status, and respondents' gender, an interaction between racial composition and
      relationship status was found. Implications for practitioners and directions for
      future research are discussed.

PMID- 23554542
TI  - On Inference for Kendall's tau within a Longitudinal Data Setting.
AB  - Kendall's tau is a non-parametric measure of correlation based on ranks and is
      used in a wide range of research disciplines. Although methods are available for
      making inference about Kendall's tau, none has been extended to modeling multiple
      Kendall's taus arising in longitudinal data analysis. Compounding this problem is
      the pervasive issue of missing data in such study designs. In this paper, we
      develop a novel approach to provide inference about Kendall's tau within a
      longitudinal study setting under both complete and missing data. The proposed
      approach is illustrated with simulated data and applied to an HIV prevention
      study.

PMID- 23554543
TI  - Verb Transitivity Bias Affects On-line Sentence Reading in People with Aphasia.
AB  - BACKGROUND: Studies of sentence comprehension in non-disordered populations have
      convincingly demonstrated that probabilistic cues influence on-line syntactic
      processing. One well-studied cue is verb argument structure bias, which refers to
      the probability that a verb will occur in a particular syntactic frame. According
      to the Lexical Bias Hypothesis, people with aphasia have difficulty understanding
      sentences in which the verb's argument structure bias conflicts with the sentence
      structure (e.g., a transitively biased verb in an intransitive sentence). This
      hypothesis may provide an account of why people with aphasia have difficulty
      understanding both simple and complex sentences. AIMS: The purpose of this study
      was to test the Lexical Bias Hypothesis using an on-line measure of written
      sentence comprehension, self-paced reading. METHODS PROCEDURES: The participants
      were ten people with aphasia and ten non-brain-damaged controls. The stimuli were
      syntactically simple transitive and intransitive sentences that contained
      transitively- or intransitively-biased verbs. For example, the transitively
      biased verb "called" appeared in sentences such as "The agent called (the writer)
      from overseas to make an offer." The intransitively-biased verb "danced" appeared
      in sentences such as "The couple danced (the tango) every Friday night last
      summer." OUTCOMES RESULTS: Both groups' reading times for critical segments were
      longer when the verb's transitivity bias did not match the sentence structure,
      particularly in intransitive sentences. CONCLUSIONS: The results were generally
      consistent with the Lexical Bias Hypothesis, and demonstrated that lexical biases
      affect on-line processing of syntactically simple sentences in people with
      aphasia and controls.

PMID- 23554544
TI  - Conformational Isomerism of trans-[Pt(NH2C6H11)2I2] and the Classical Wernerian
      Chemistry of [Pt(NH2C6H11)4]X2 (X = Cl, Br, I).
AB  - X-ray crystallographic analysis of the compound trans-[Pt(NH2C6H11)2I2] revealed
      the presence of two distinct conformers within one crystal lattice. This compound
      was studied by variable temperature NMR spectroscopy to investigate the dynamic
      interconversion between these isomers. The results of this investigation were
      interpreted using physical (CPK) and computational (molecular mechanics and
      density functional theory) models. The conversion of the salts [Pt(NH2C6H11)4]X2
      into trans-[Pt(NH2C6H11)2X2] (X = Cl, Br, I) was also studied and is discussed
      here with an emphasis on parallels to the work of Alfred Werner.

PMID- 23554545
TI  - Defining Adult Experiences: Perspectives of a Diverse Sample of Young Adults.
AB  - This study explored the roles and psychological experiences identified as
      defining adult moments using mixed methods with a racially, ethnically, and
      socioeconomically diverse sample of young adults both enrolled and not enrolled
      in college (N = 726; ages 18-35). First, we evaluated results from a single
      survey item that asked participants to rate how adult they feel. Consistent with
      previous research, the majority of participants (56.9%) reported feeling
      "somewhat like an adult," and older participants had significantly higher
      subjective adulthood, controlling for other demographic variables. Next, we
      analyzed responses from an open-ended question asking participants to describe
      instances in which they felt like an adult. Responses covered both traditional
      roles (e.g., marriage, childbearing; 36.1%) and nontraditional social roles and
      experiences (e.g., moving out of parent's home, cohabitation; 55.6%). Although we
      found no differences by age and college status in the likelihood of citing a
      traditional or nontraditional role, participants who had achieved more
      traditional roles were more likely to cite them in their responses. In addition,
      responses were coded for psychological experiences, including responsibility for
      self (19.0%), responsibility for others (15.3%), self-regulation (31.1%), and
      reflected appraisals (5.1%). Older participants were significantly more likely to
      include self-regulation and reflected appraisals, whereas younger participants
      were more likely to include responsibility for self. College students were more
      likely than noncollege students to include self-regulation and reflected
      appraisals. Implications for research and practice are discussed.

PMID- 23554547
TI  - HIDDEN DISPARITIES: HOW COURSES AND CURRICULA SHAPE OPPORTUNITIES IN MATHEMATICS
      DURING HIGH SCHOOL.
AB  - Efforts to promote academic achievement by increasing access to courses,
      especially in mathematics, may mask educational disparities if variations in
      curriculum are not also monitored. A multi-dimensional description of students'
      mathematics curricula during high school was obtained from analyses of surveys,
      transcripts, and textbooks collected for a nationally representative study of
      adolescents during the mid-1990s. Few gaps in the number of years or credits in
      mathematics coursework were found. However, the quantity and cognitive challenge
      of instructional materials in textbooks adopted for those courses differed
      significantly both across and within mathematics tracks. Differences in the
      quality of curriculum accumulating during high school were also related to
      parents' education level. Reducing such gaps in learning opportunities would
      require teachers to supplement adopted instructional materials to ensure that all
      students receive a high quality mathematics curriculum.

PMID- 23554546
TI  - Subclinical cardiovascular system changes in obese patients with juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: We aimed to determine the prevalence of excess body mass in juvenile
      idiopathic arthritis (JIA) children and to investigate the influence of obesity
      into the early, subclinical changes in cardiovascular system in these patients.
      METHODS: Fifty-eight JIA patients, aged median 13 years, were compared to 36
      healthy controls. Traditional cardiovascular risk factors and inflammatory
      markers (hsCRP, IL-6, TNF alpha, adiponectin) were studied together with IMT
      (intima-media thickness), FMD (flow mediated dilation), and LVMi (left ventricle
      mass index) as surrogate markers of subclinical atherosclerosis. RESULTS:
      Thirteen JIA children (22%) were obese and had increased systolic blood pressure,
      cholesterol, triglycerides, insulin, HOMA, hsCRP, and IL-6 compared to nonobese
      JIA and controls. FMD was decreased compared to nonobese JIA and controls,
      whereas IMT and LVMi were increased. In multivariate regression analysis, TNF
      alpha, SDS-BMI, and systolic blood pressure were independent predictors of early
      CV changes in JIA. CONCLUSIONS: Coincident obesity is common in JIA children and
      is associated with insulin resistance, dyslipidemia, and increased levels of
      inflammatory markers leading to early changes in cardiovascular system. Thus,
      medical care of children with JIA should include strategies preventing
      cardiovascular disease by maintenance of adequate body weight.

PMID- 23554548
TI  - Efficacy, Safety, and Long-Term Follow-Up Results of EUS-Guided Transmural
      Drainage for Pancreatic Pseudocyst.
AB  - Background and Aim. EUS-guided transmural drainage (EUS-GTD) is now considered a
      minimally invasive and effective alternative to surgery for drainage of
      symptomatic pancreatic pseudocysts. However, the technique is rather difficult,
      and sometimes serious complications occur to patients undergoing this procedure.
      We retrospectively evaluated efficacy, safety, and long-term follow-up results of
      EUS-GTD for pancreatic pseudocyst. Methods. Sixty-seven patients with pancreatic
      pseudocyst who underwent EUS-GTD from April 2000 to March 2011 were enrolled. We
      retrospectively evaluated (1) technical success, (2) clinical success, (3)
      adverse event of procedure, and (4) long-term follow-up results. Results. Total
      technical success rate was 88%. Ninety-one percent of external drainage, 79% of
      internal drainage, and 66% of puncture and aspiration only achieved clinical
      success. There was only one case with an adverse event, perforation (1.5%). The
      case required emergency operation. Total recurrence rate was 23.9%. Median follow
      up period was 33.9 months. The recurrence rates in the cases of stent remaining,
      spontaneously dislodged, removed on schedule, external tube removal, and
      aspiration only were 10.0%, 12.5%, 42.9%, 50%, and 0%, respectively. Conclusion.
      EUS-GTD is a relatively safe and effective therapeutic method. However, further
      analysis should be done by larger series to determine the method of EUS-GTD for
      pancreatic pseudocyst.

PMID- 23554549
TI  - Transient swelling, spreading, and drug delivery by a dissolved anti-HIV
      microbicide-bearing film.
AB  - There is a widespread agreement that more effective drug delivery vehicles with
      more alternatives, as well as better active pharmaceutical ingredients (APIs),
      must be developed to improve the efficacy of microbicide products. For instance,
      in tropical regions, films are more appropriate than gels due to better stability
      of drugs at extremes of moisture and temperature. Here, we apply fundamental
      fluid mechanical and physicochemical transport theory to help better understand
      how successful microbicide API delivery depends upon properties of a film and the
      human reproductive tract environment. Several critical components of successful
      drug delivery are addressed. Among these are: elastohydrodynamic flow of a
      dissolved non-Newtonian film; mass transfer due to inhomogeneous dilution of the
      film by vaginal fluid contacting it along a moving boundary (the locally
      deforming vaginal epithelial surface); and drug absorption by the epithelium.
      Local rheological properties of the film are dependent on local volume fraction
      of the vaginal fluid. We evaluated this experimentally, delineating the way that
      constitutive parameters of a shear-thinning dissolved film are modified by
      dilution. To develop the mathematical model, we integrate the Reynolds
      lubrication equation with a mass conservation equation to model diluting fluid
      movement across the moving vaginal epithelial surface and into the film. This is
      a complex physicochemical phenomenon that is not well understood. We explore time
      and space-varying boundary flux model based upon osmotic gradients. Results show
      that the model produces fluxes that are comparable to experimental data. Further
      experimental characterization of the vaginal wall is required for a more precise
      set of parameters and a more sophisticated theoretical treatment of epithelium.

PMID- 23554551
TI  - Predicting co-morbidities in chemically sensitive individuals from exhaled breath
      analysis.
AB  - The exhaled breath of more than four hundred patients who presented at the
      Environmental Health Center - Dallas with chemical sensitivity conditions were
      analyzed for the relative abundance of their breath chemical composition by gas
      chromatography and mass spectrometry for volatile and semi-volatile organic
      compounds. All presenting patients had no fewer than four and as many as eight co
      morbid conditions. Surprisingly, almost all the exhaled breath analyses showed
      the presence of a preponderance of lipophilic aliphatic and aromatic
      hydrocarbons. The hydrophilic compounds present were almost entirely of natural
      origin, i.e. expected metabolites of foods. The lipophile, primarily C3 to C16
      hydrocarbons and believed to have come from inhalation of polluted air, were, in
      all cases, present at concentrations far below those known to be toxic to humans,
      but caused sensitivity and signs of chemical overload. The co-morbid health
      effects observed are believed to be caused by the sequential absorption of
      lipophilic and hydrophilic chemicals; an initial absorption and retention of
      lipophile followed by a subsequent absorption of hydrophilic species facilitated
      by the retained lipophile to produce chemical mixtures that are toxic at very low
      levels. It is hypothesized that co-morbid conditions in chemically sensitive
      individuals can be predicted from analysis of their exhaled breath.

PMID- 23554550
TI  - Effects of xenobiotics on total antioxidant capacity.
AB  - The objective of this article was to review the effects of xenobiotics on total
      antioxidant capacity (TAC). Measurement of TAC is appropriate for evaluation of
      the total antioxidant defenses of blood, cells, and different kinds of tissues
      and organs. TAC is reduced by alcoholism, smoking, and exposure to radiation,
      herbicides, carbon monoxide, carbon tetrachloride, lead, arsenic, mercury,
      cadmium, aluminum, and other toxic elements. The test is also an important tool
      in evaluating environmental and occupational exposure.

PMID- 23554552
TI  - Influence of iron and copper consumption on weight gain and oxidative stress in
      adipose tissue of Wistar rats.
AB  - The aim of the present study was to assess the effect of iron and copper
      consumption on weight gain and development of oxidative stress in adipose tissue
      of rats. Control rats obtained pure drinking water. Iron-treated groups of
      animals obtained FeSO4*12H2O with drinking water in concentrations of 3 and 6
      mg/l, while copper-treated rats obtained CuSO4 in concentrations of 4.88 and 9.76
      mg/l. The animals of the 6th group received a mixture of FeSO4*12H2O and CuSO4 in
      the respective concentrations of 3 and 4.88 mg/l in drinking water. All animals
      received a standard chow. The final weight of rats from all the experimental
      groups, especially in those obtaining the combination of iron and cooper,
      exceeded the control values. Maximal weight of fat pads was observed in animals
      receiving drinking water with 3 mg/l FeSO4*12H2O, 4.88 and 9.76 mg/l CuSO4, and
      the mixture of FeSO4*12H2O and CuSO4. The maximal intensity of free radical
      processes, as estimated by the concentration of fluorescent modified amino acids
      and the intensity of chemiluminescence in adipose tissue homogenates, was
      observed in rats obtaining iron in the concentration of 3 mg/l in the drinking
      water.

PMID- 23554553
TI  - Evaluation of biochemical, hematological and oxidative parameters in mice exposed
      to the herbicide glyphosate-Roundup((r)).
AB  - We evaluated the toxicity of hepatic, hematological, and oxidative effects of
      glyphosate-Roundup((r)) on male and female albino Swiss mice. The animals were
      treated orally with either 50 or 500 mg/kg body weight of the herbicide, on a
      daily basis for a period of 15 days. Distilled water was used as control
      treatment. Samples of blood and hepatic tissue were collected at the end of the
      treatment. Hepatotoxicity was monitored by quantitative analysis of the serum
      enzymes ALT, AST, and gamma-GT and renal toxicity by urea and creatinine. We also
      investigated liver tissues histopathologically. Alterations of hematological
      parameters were monitored by RBC, WBC, hemoglobin, hematocrit, MCV, MCH, and
      MCHC. TBARS (thiobarbituric acid reactive substances) and NPSH (non-protein
      thiols) were analyzed in the liver to assess oxidative damage. Significant
      increases in the levels of hepatic enzymes (ALT, AST, and gamma-GT) were observed
      for both herbicide treatments, but no considerable differences were found by
      histological analysis. The hematological parameters showed significant
      alterations (500 mg/kg body weight) with reductions of RBC, hematocrit, and
      hemoglobin, together with a significant increase of MCV, in both sexes of mice.
      In males, there was an important increase in lipid peroxidation at both dosage
      levels, together with an NPSH decrease in the hepatic tissue, whereas in females
      significant changes in these parameters were observed only at the higher dose
      rate. The results of this study indicate that glyphosate-Roundup((r)) can promote
      hematological and hepatic alterations, even at subacute exposure, which could be
      related to the induction of reactive oxygen species.

PMID- 23554554
TI  - Comparison in the efficiency of different murine lines for genotoxicity assays.
AB  - The aim of this research was to compare the efficiency of different murine lines
      for genotoxicity assays. Rats and mice of different murine lines were used. The
      spontaneous and induced indexes were evaluated according to alkaline comet assay
      of peripheral blood leukocytes, micronucleus and chromosomic aberration assay of
      bone marrow cell, and sperm head morphology assay. In most of the evaluated
      assays the line of Balb/c mice turned out to be the ideal biomodel, with less
      spontaneous indexes and high induced indexes to the mutagen used; allowing to
      detect in a narrow error margin those substances that are classified of very low
      genotoxicity. These results demonstrate that genetically the line of Balb/c mice
      in both sexes is more stable than the other ones evaluated. This suggests the use
      of the Balb/c line on in vivo genotoxicity assay will increase sensibility and
      robustness.

PMID- 23554555
TI  - Simultaneous determination of cytochrome P450 1A, 2A and 3A activities in porcine
      liver microsomes.
AB  - The aim of this study was to develop a robust method for the simultaneous
      determination of the activities of three porcine CYP450 enzymes in hepatic
      microsomes. A cocktail consisting of three selective CYP450 probe substrates, 7
      ethoxyresorufin (CYP1A), coumarin (CYP2A) and 7-benzyloxy-4
      trifluoromethylcoumarin (BFC; CYP3A), was incubated with porcine liver
      microsomes. The presence of 7-ethoxyresorufin appears to significantly influence
      the kinetics of coumarin hydroxylation and BFC O-debenzylation. These results
      indicate that the use of 7-ethoxyresorufin in substrate cocktails together with
      coumarin and BFC should be avoided.

PMID- 23554556
TI  - Sex differences in endothelial function of aged hypertriglyceridemic rats -
      effect of atorvastatin treatment.
AB  - The aim of the study was to test the hypothesis that the effect of atorvastatin
      on endothelium-dependent relaxation of the superior mesenteric artery (SMA) may
      differ in male vs. female aged hypertriglyceridemic rats (HTGs). Experiments were
      performed on 11-month-old male and female Prague hereditary HTGs. Atorvastatin
      (ATO) was administered p.o. in the dose of 0.30 mg/100g/day. Controls received
      vehiculum. After two months of ATO administration blood pressure, serum
      triglycerides (TG) and total cholesterol (CHOL) were determined. Endothelial
      function of SMA was studied in vitro using evaluation of relaxant responses of
      precontracted SMA to acetylcholine. The serum TG of control male HTGs were found
      to be statistically higher than those of female controls, while CHOL and blood
      pressure did not share gender differences. Responses of SMA of female control
      HTGs were statistically decreased compared to their male counterparts. ATO
      treatment induced decrease in blood pressure and TG of both males and females,
      yet CHOL values were reduced only in females. The protective effect of ATO on SMA
      endothelial function was much more pronounced in females compared to males. We
      conclude that vascular endothelial dysfunction of aged HTG rats is more severe
      and more attenuated by ATO in females compared to males. The protective effect of
      ATO on vascular endothelial function does not seem to depend solely on its lipid
      lowering action.

PMID- 23554557
TI  - Effect of thimerosal, methylmercury, and mercuric chloride in Jurkat T Cell Line.
AB  - Mercury is a ubiquitous environmental toxicant that causes a wide range of
      adverse health effects in humans. Three forms of mercury exist: elemental,
      inorganic and organic. Each of them has its own profile of toxicity. The aim of
      the present study was to determine the effect of thimerosal, a topical antiseptic
      and preservative in vaccines routinely given to children, methyl mercury, and
      mercuric chloride on cellular viability measured by MTT in Jurkat T cells, a
      human T leukemia cell line. The treatment of Jurkat T cells with thimerosal
      caused a significant decrease in cellular viability at 1 MUM (25%, p<0.05; IC50:
      10 MUM). Methyl mercury exhibited a significant decrease in cellular viability at
      50 MUM (33%, p<0.01; IC50: 65 MUM). Mercuric chloride (HgCl2) did not show any
      significant change in cellular survival. Our findings showed that contrary to
      thimerosal and methyl mercury, mercuric chloride did not modify Jurkat T cell
      viability.

PMID- 23554559
TI  - Acute toxicity of vipoxin and its components: is the acidic component an
      "inhibitor" of PLA2 toxicity?
AB  - Vipoxin is a heterodimeric neurotoxin isolated from the venom of the Bulgarian
      long-nosed viper Vipera ammodytes meridionalis. Vipoxin represents a noncovalent
      association of two subunits - a basic and toxic phospholipase A2 enzyme, and an
      acidic non-enzymatic component (vipoxin's acidic component). It was postulated
      that the phospholipase A2 subunit was more toxic than the whole vipoxin complex
      and the function of the acidic component was to reduce the enzymatic and toxic
      activities of the basic phospholipase A2. In the present study, we report new
      data on the acute toxicity (LD50) of vipoxin and its individual separated
      components. Vipoxin LD50 (mice, i.p. and i.v.) values were found to be 0.7-1.2
      mg/kg b.w. (i.p.) and 0.9-1.3 mg/kg b.w. (i.v.). The established LD50 values for
      the separated pure phospholipase A2 subunit are higher - 10.0-13.0 mg/kg b.w
      (i.p.) and 2.2-3.0 mg/kg b.w. (i.v.), i.e. the individual phospholipase A2
      subunit displays less toxic activity than vipoxin, contrary to the data published
      in the literature. The reconstituted vipoxin complex (obtained after preliminary
      incubation of pure separated phospholipase A2 and acidic component showed enzyme
      activity and toxicity comparable to that of the native vipoxin complex. Addition
      of acidic component to the phospholipase A2 subunit showed a positive effect on
      the enzymatic activity, reaching maximal enzyme reaction rate of acidic component
      to phospholipase A2 molar ratio of 0.8:1 on using 4-nitro-3-octanoyloxy-benzoic
      acid as substrate. For the first time we showed that the acidic subunit was
      absolutely required for the toxic activity of vipoxin. Based on the obtained
      results, we assume that the function of the acidic component is to stabilize the
      neurotoxin's quaternary structure, required for its toxic and enzymatic
      activities, similarly to the role of the acidic component of crotoxin.

PMID- 23554558
TI  - Teratology - past, present and future.
AB  - Teratology is the science that studies the causes, mechanisms, and patterns of
      abnormal development. The authors present an updated overview of the most
      important milestones and stages of the development of modern teratology.
      Development of knowledge and society led to the recognition that causes of
      congenital developmental disorders (CDDs) might be caused by various mechanical
      effects, foetal diseases, and retarded or arrested development of the embryo and
      foetus. Based on the analysis of the historical development of hypotheses and
      theories representing a decisive contribution to this field, we present a survey
      of the six Wilson's fundamental principles of teratology. The aim of observing
      these principles is to get insight into developmental relations and to understand
      mechanisms of action on the level of cell populations (elementary morphogenetic
      processes), tissues and organs. It is important to realise that any negative
      intervention into the normal course of these processes, either on genetic or non
      genetic basis, inevitably leads to a sequence of subsequent changes resulting in
      CDDs. Moreover, the classical toxicologic monotonic dose-response paradigm
      recently has been challenged by the so-called "low dose-hypothesis", particularly
      in the case of endocrine active substances. These include some pesticides,
      dioxins, polychlorobiphenyls (PCBs), and bisphenol A. Despite modern approaches
      of molecular biology and genetics, along with top diagnostic techniques, we are
      still not able to identify the actual cause in more than 65 to 70% of all
      congenital defects classified as having an unknown etiology. Today CDDs include
      any birth defect, either morphological, biochemical, or behavioural.

PMID- 23554560
TI  - Distribution of opiate alkaloids in brain tissue of experimental animals.
AB  - The present study examined regional distribution of opiate alkaloids from seized
      heroin in brain regions of experimental animals in order to select parts with the
      highest content of opiates. Their analysis should contribute to resolve causes of
      death due to heroin intake. The tests were performed at different time periods
      (5, 15, 45 and 120 min) after male and female Wistar rats were treated with
      seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6
      acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain
      regions known for their high concentration of u-opiate receptors: cortex,
      brainstem, amygdala and basal ganglia, by using gas chromatography-mass
      spectrometry (GC-MS). The highest content of opiate alkaloids in the brain tissue
      of female animals was found 15 min and in male animals 45 min after treatment.
      The highest content of opiates was determined in the basal ganglia of the animals
      of both genders, indicating that this part of brain tissue presents a reliable
      sample for identifying and assessing contents of opiates after heroin intake.

PMID- 23554561
TI  - Effects of hydrogen peroxide on diazepam and xylazine sedation in chicks.
AB  - Oxidative stress may cause various neuronal dysfunctions and modulate responses
      to many centrally acting drugs. This study examines the effects of oxidative
      stress produced by hydrogen peroxide (H2O2) on sedation induced by diazepam or
      xylazine as assessed in 7-14 day-old chicks. Day-old chicks were provided with
      either plane tap water (control group) or H2O2 in tap water as 0.5% v/v drinking
      solution for two weeks in order to produce oxidative stress. Spectrophotometric
      methods were used to determine glutathione and malondialdehyde concentrations in
      plasma and whole brain. Drug-induced sedation in the chicks was assessed by
      monitoring the occurrence of signs of sedation manifested as drooping of the
      head, closed eyelids, reduced motility or immotility, decreased distress calls,
      and recumbency. The latency to onset of sedation and its duration were also
      recorded. H2O2 treatment for two weeks significantly decreased glutathione and
      increased malondialdehyde concentrations in plasma and whole brain of the chicks
      on days 7, 10 and 14 as compared with respective age-matched control groups. H2O2
      decreased the median effective doses of diazepam and xylazine for the induction
      of sedation in chicks by 46% and 63%, respectively. Injection of diazepam at 2.5,
      5 and 10 mg/kg, i.m. or xylazine at 2, 4 and 8 mg/kg, i.m. induced sedation in
      both control and H2O2-treated chicks in a dose dependent manner, manifested by
      the above given signs of sedation. H2O2 significantly decreased the latency to
      onset of sedation in chicks treated with diazepam at 5 and 10 mg/kg, increased
      the duration of sedation and prolonged the total recovery time in comparison with
      respective non-stressed control chicks. A similar trend occurred with xylazine in
      the H2O2-treated chicks, though the differences from control counterparts did not
      attain the statistical significance, except for the recovery time of the lowest
      dose of the drug. The data suggest that H2O2-induced oxidative stress sensitizes
      the chicks to the depressant action of the sedatives diazepam and xylazine.
      Further studies are needed to examine the potential role of oxidative stress in
      modulating the actions of therapeutic agents on the brain.

PMID- 23554562
TI  - Toxicity of a plant based mosquito repellent/killer.
AB  - The mission to make humans less attractive to mosquitoes has fuelled decades of
      scientific research on mosquito behaviour and control. The search for the perfect
      topical insect repellent/killer continues. This analysis was conducted to review
      and explore the scientific information on toxicity produced by the
      ingredients/contents of a herbal product. In this process of systemic review the
      following methodology was applied. By doing a MEDLINE search with key words of
      selected plants, plant based insect repellents/killers pertinent articles
      published in journals and authentic books were reviewed. The World Wide Web and
      the Extension Toxicity Network database (IPCS-ITOX) were also searched for
      toxicology data and other pertinent information. Repellents do not all share a
      single mode of action and surprisingly little is known about how repellents act
      on their target insects. Moreover, different mosquito species may react
      differently to the same repellent. After analysis of available data and
      information on the ingredient, of the product in relation to medicinal uses,
      acute and chronic toxicity of the selected medicinal plants, it can be concluded
      that the ingredients included in the herbal product can be used as active agents
      against mosquitoes. If the product which contains the powder of the above said
      plants is applied with care and safety, it is suitable fo use as a mosquito
      repellent/killer.

PMID- 23554563
TI  - Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress,
      hematological and enzymatic parameters in cadmium toxicity induced rat model.
AB  - We investigated the protective role of ceftriaxone plus sulbactam with VRP1034
      (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities
      and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male
      rats were divided into three groups of eight rats each. The control group
      received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body
      weight) through gastric gavage for 21 days. Group III received CdCl2 and was
      treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The
      hematological, biochemical, lipid peroxidation levels and enzymatic parameters
      were measured in plasma and tissues (brain, liver and kidney) of all groups. The
      Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our
      findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde
      (p<0.001) and myloperoxidase (MPO) levels along with significantly increased
      hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant
      enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone
      plus sulbactam with VRP1034 treated group as compared to cadmium exposed group.
      Delta aminolevulinate dehydratase (delta-ALAD) activity was significantly
      (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034
      treated group as compared with cadmium exposed group. The levels of hepatic and
      renal parameters were significantly (p<0.001) decreased in ceftriaxone plus
      sulbactam with VRP1034 treated group as compared to cadmium exposed group. These
      findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent
      free radical scavenger and exhibits metal chelating properties that reduce free
      radical mediated tissue injury and prevent dysfunction of hepatic and renal
      organs during metal intoxication.

PMID- 23554564
TI  - Assessment of genotoxicity and antigenotoxicity of an aqueous extract of
      Cleistocalyx nervosum var. paniala in in vitro and in vivo models.
AB  - Cleistocalyx nervosum var. paniala, an edible fruit found in Northern Thailand,
      contains high amounts of phenolic compounds with in vitro antioxidant activity.
      The aqueous extract of the ripe fruit was evaluated for its safety and beneficial
      effects using genotoxicity and toxicity tests. The C. nervosum extract was not
      only non-mutagenic in Salmonella typhimurium strains TA98 and TA100 in the
      presence and absence of metabolic activation, but exhibited also moderate
      antimutagenic effects against aflatoxin B1 and 2-amino-3,4-dimethylimidazo[4,5
      f]quinoline-induced mutagenesis. Electrospray ionization-mass spectrometric
      analysis revealed the major anthocyanins, which included cyanidin-3,5
      diglucoside, cyanidin-3-glucoside and cyanidin-5-glucoside. The administration of
      C. nervosum at concentration of 5,000 mg/kg bw did not induce acute toxicity in
      rats. A liver micronucleus test was performed to detect clastogenicity and
      anticlastogenicity. The extract in the dose of 1,000 mg/kg did not cause
      micronucleus formation in the liver of rats. Furthermore, in rats administered
      100-1,000 mg/kg of the extract, no anticlastogenic effect against
      diethylnitrosamine-induced hepatic micronucleus formation was observed. These
      studies provide data concerning the safety and antimutagenic potency of an
      aqueous extract of C. nervosum fruit.

PMID- 23554565
TI  - Antioxidant and hepatoprotective effect of Garcinia indica fruit rind in ethanol
      induced hepatic damage in rodents.
AB  - The protective effects of aqueous extracts of the fruit rind of Garcinia indica
      (GIE) on ethanol-induced hepatotoxicity and the probable mechanisms involved in
      this protection were investigated in rats. Liver damage was induced in rats by
      administering ethanol (5 g/kg, 20% w/v p.o.) once daily for 21 days. GIE at 400
      mg/kg and 800 mg/kg and the reference drug silymarin (200 mg/kg) were
      administered orally for 28 days to ethanol treated rats, this treatment beginning
      7 days prior to the commencement of ethanol administration. Levels of marker
      enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
      alkaline phosphatase (ALP)), triglyceride (sTG), albumin (Alb) and total protein
      (TP) were evaluated in serum. Antioxidant parameters (reduced glutathione (GSH),
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and
      glutathione reductase (GR)), hepatic triglycerides (hTG) and the lipid
      peroxidation marker malondialdehyde (MDA) were determined in liver. GIE and
      silymarin elicited significant hepatoprotective activity by attenuating the
      ethanol-elevated levels of AST, ALT, ALP, sTG, hTG and MDA and restored the
      ethanol-depleted levels of GSH, SOD, CAT, GPx, GR, Alb and TP. GIE 800 mg/kg
      demonstrated greater hepatoprotection than GIE 400 mg/kg. The present findings
      indicate that hepatoprotective effects of GIE in ethanol-induced oxidative damage
      may be due to an augmentation of the endogenous antioxidants and inhibition of
      lipid peroxidation in liver.

PMID- 23554566
TI  - A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial
      Sarcoma.
AB  - Background. Patients with recurrent synovial sarcomas have few options for
      systemic therapy. Since they express large amounts of endogenous CT (cancer
      testis) antigens such as NY-ESO-1, we investigated the clinical activity of
      single agent anti-CTLA4 antibody ipilimumab in patients with advanced or
      metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used
      to determine if there was sufficient activity to pursue further. The primary
      endpoint was tumor response rate by RECIST 1.0. Patients were treated with
      ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then
      restaged. Retreatment was possible for patients receiving an extra three-week
      break from therapy. Sera and peripheral blood mononuclear cells were collected
      before and during therapy to assess NY-ESO-1-specific immunity. Results. Six
      patients were enrolled and received 1-3 cycles of ipilimumab. All patients showed
      clinical or radiological evidence of disease progression after no more than three
      cycles of therapy, for a RECIST response rate of 0%. The study was stopped for
      slow accrual, lack of activity, and lack of immune response. There was no
      evidence of clinically significant either serologic or delayed type
      hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion.
      Despite high expression of CT antigens by synovial sarcomas of patients treated
      in this study, there was neither clinical benefit nor evidence of anti-CT antigen
      serological responses. Assessment of the ability of synovial sarcoma cell lines
      to present cancer-germ cell antigens may be useful in determining the reason for
      the observed lack of immunological or clinical activity.

PMID- 23554568
TI  - Persistent organic pollutants in fresh water ecosystems.

PMID- 23554567
TI  - Ribonucleoproteins in archaeal pre-rRNA processing and modification.
AB  - Given that ribosomes are one of the most important cellular macromolecular
      machines, it is not surprising that there is intensive research in ribosome
      biogenesis. Ribosome biogenesis is a complex process. The maturation of ribosomal
      RNAs (rRNAs) requires not only the precise cleaving and folding of the pre-rRNA
      but also extensive nucleotide modifications. At the heart of the processing and
      modifications of pre-rRNAs in Archaea and Eukarya are ribonucleoprotein (RNP)
      machines. They are called small RNPs (sRNPs), in Archaea, and small nucleolar
      RNPs (snoRNPs), in Eukarya. Studies on ribosome biogenesis originally focused on
      eukaryotic systems. However, recent studies on archaeal sRNPs have provided
      important insights into the functions of these RNPs. This paper will introduce
      archaeal rRNA gene organization and pre-rRNA processing, with a particular focus
      on the discovery of the archaeal sRNP components, their functions in nucleotide
      modification, and their structures.

PMID- 23554569
TI  - Hepatitis C virus adaptation to T-cell immune pressure.
AB  - Replication of the hepatitis C virus (HCV) is an error-prone process. This high
      error rate results in the emergence of viral populations (quasispecies) within
      hosts and contributes to interhost variability. Numerous studies have
      demonstrated that both viral and host factors contribute to this viral diversity,
      which can ultimately affect disease outcome. As the host's immune response is an
      important correlate of infection outcome for HCV, many of these viral variations
      are strongly influenced by T-cell immune pressure and accordingly constitute an
      efficient strategy to subvert such pressures (viral adaptations). This paper will
      review the data on viral diversity observed between and within hosts infected
      with HCV from the acute to the chronic stage of infection and will focus on viral
      adaptation to the host's T-cell immune response.

PMID- 23554570
TI  - A comparative genomic study in schizophrenic and in bipolar disorder patients,
      based on microarray expression profiling meta-analysis.
AB  - Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of
      the global population constitute two severe mental disorders. The
      catecholaminergic and the serotonergic pathways have been proved to play an
      important role in the development of schizophrenia, bipolar disorder, and other
      related psychiatric disorders. The aim of the study was to perform and interpret
      the results of a comparative genomic profiling study in schizophrenic patients as
      well as in healthy controls and in patients with bipolar disorder and try to
      relate and integrate our results with an aberrant amino acid transport through
      cell membranes. In particular we have focused on genes and mechanisms involved in
      amino acid transport through cell membranes from whole genome expression
      profiling data. We performed bioinformatic analysis on raw data derived from four
      different published studies. In two studies postmortem samples from prefrontal
      cortices, derived from patients with bipolar disorder, schizophrenia, and control
      subjects, have been used. In another study we used samples from postmortem
      orbitofrontal cortex of bipolar subjects while the final study was performed
      based on raw data from a gene expression profiling dataset in the postmortem
      superior temporal cortex of schizophrenics. The data were downloaded from NCBI's
      GEO datasets.

PMID- 23554571
TI  - Osteoporotic hip fractures: current issues and evolving concepts of surgical
      management.

PMID- 23554573
TI  - Secretion and signaling activities of lipoprotein-associated hedgehog and non
      sterol-modified hedgehog in flies and mammals.
AB  - Hedgehog (Hh) proteins control animal development and tissue homeostasis. They
      activate gene expression by regulating processing, stability, and activation of
      Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and
      spread through tissue, despite becoming covalently linked to sterol during
      processing. Multiple mechanisms have been proposed to release Hh proteins in
      distinct forms; in Drosophila, lipoproteins facilitate long-range Hh mobilization
      but also contain lipids that repress the pathway. Here, we show that mammalian
      lipoproteins have conserved roles in Sonic Hedgehog (Shh) release and pathway
      repression. We demonstrate that lipoprotein-associated forms of Hh and Shh
      specifically block lipoprotein-mediated pathway inhibition. We also identify a
      second conserved release form that is not sterol-modified and can be released
      independently of lipoproteins (Hh-N*/Shh-N*). Lipoprotein-associated Hh/Shh and
      Hh-N*/Shh-N* have complementary and synergistic functions. In Drosophila wing
      imaginal discs, lipoprotein-associated Hh increases the amount of full-length Ci,
      but is insufficient for target gene activation. However, small amounts of non
      sterol-modified Hh synergize with lipoprotein-associated Hh to fully activate the
      pathway and allow target gene expression. The existence of Hh secretion forms
      with distinct signaling activities suggests a novel mechanism for generating a
      diversity of Hh responses.

PMID- 23554575
TI  - A novel path to obesity.

PMID- 23554574
TI  - Neuronal expression of glucosylceramide synthase in central nervous system
      regulates body weight and energy homeostasis.
AB  - Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function
      essentially depends on plasma membrane-located gangliosides. The present work
      demonstrates that hypothalamic integration of metabolic signals requires neuronal
      expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide
      glucosyltransferase). As a major mechanism of central nervous system (CNS)
      metabolic control, we demonstrate that GCS-derived gangliosides interacting with
      leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated
      formation of signaling metabolites in hypothalamic neurons. Furthermore,
      ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in
      response to alterations in peripheral energy signals. Consequently, mice with
      inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide
      glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower
      sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg
      delivery to the arcuate nucleus (Arc) significantly ameliorated obesity,
      specifying gangliosides as seminal components for hypothalamic regulation of body
      energy homeostasis.

PMID- 23554576
TI  - Positively charged residues are the major determinants of ribosomal velocity.
AB  - Both for understanding mechanisms of disease and for the design of transgenes, it
      is important to understand the determinants of ribosome velocity, as changes in
      the rate of translation are important for protein folding, error attenuation, and
      localization. While there is great variation in ribosomal occupancy along even a
      single transcript, what determines a ribosome's occupancy is unclear. We examine
      this issue using data from a ribosomal footprinting assay in yeast. While codon
      usage is classically considered a major determinant, we find no evidence for
      this. By contrast, we find that positively charged amino acids greatly retard
      ribosomes downstream from where they are encoded, consistent with the suggestion
      that positively charged residues interact with the negatively charged ribosomal
      exit tunnel. Such slowing is independent of and greater than the average effect
      owing to mRNA folding. The effect of charged amino acids is additive, with
      ribosomal occupancy well-predicted by a linear fit to the density of positively
      charged residues. We thus expect that a translated poly-A tail, encoding for
      positively charged lysines regardless of the reading frame, would act as a
      sandtrap for the ribosome, consistent with experimental data.

PMID- 23554577
TI  - Positive charges put the brakes on ribosomes.

PMID- 23554578
TI  - Surveillance Programme of IN-patients and Epidemiology (SPINE): implementation of
      an electronic data collection tool within a large hospital in Malawi.
AB  - Miguel Sanjoaquin and colleagues describe their experience of setting up an
      electronic patient records system in a large referral hospital in Blantyre,
      Malawi.

PMID- 23554579
TI  - The cost and impact of scaling up pre-exposure prophylaxis for HIV prevention: a
      systematic review of cost-effectiveness modelling studies.
AB  - BACKGROUND: Cost-effectiveness studies inform resource allocation, strategy, and
      policy development. However, due to their complexity, dependence on assumptions
      made, and inherent uncertainty, synthesising, and generalising the results can be
      difficult. We assess cost-effectiveness models evaluating expected health gains
      and costs of HIV pre-exposure prophylaxis (PrEP) interventions. METHODS AND
      FINDINGS: We conducted a systematic review comparing epidemiological and economic
      assumptions of cost-effectiveness studies using various modelling approaches. The
      following databases were searched (until January 2013): PubMed/Medline, ISI Web
      of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region
      specific databases. We included modelling studies reporting both cost and
      expected impact of a PrEP roll-out. We explored five issues: prioritisation
      strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies
      retrieved, 13 were included. Studies modelled populations (heterosexual couples,
      men who have sex with men, people who inject drugs) in generalised and
      concentrated epidemics from Southern Africa (including South Africa), Ukraine,
      USA, and Peru. PrEP was found to have the potential to be a cost-effective
      addition to HIV prevention programmes in specific settings. The extent of the
      impact of PrEP depended upon assumptions made concerning cost, epidemic context,
      programme coverage, prioritisation strategies, and individual-level adherence.
      Delivery of PrEP to key populations at highest risk of HIV exposure appears the
      most cost-effective strategy. Limitations of this review include the partial
      geographical coverage, our inability to perform a meta-analysis, and the paucity
      of information available exploring trade-offs between early treatment and PrEP.
      CONCLUSIONS: Our review identifies the main considerations to address in
      assessing cost-effectiveness analyses of a PrEP intervention--cost, epidemic
      context, individual adherence level, PrEP programme coverage, and prioritisation
      strategy. Cost-effectiveness studies indicating where resources can be applied
      for greatest impact are essential to guide resource allocation decisions;
      however, the results of such analyses must be considered within the context of
      the underlying assumptions made. Please see later in the article for the Editors'
      Summary.

PMID- 23554580
TI  - Adapting standards: ethical oversight of participant-led health research.
AB  - As participant-led health research increases, Effy Vayena and and John Tasioulas
      examine what ethical questions are raised, and what types of standards need to be
      developed for appropriate ethical oversight for participant-led research
      projects.

PMID- 23554581
TI  - Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta
      analysis of depression, quality of life, and safety outcomes.
AB  - BACKGROUND: Atypical antipsychotic medications are widely prescribed for the
      adjunctive treatment of depression, yet their total risk-benefit profile is not
      well understood. We thus conducted a systematic review of the efficacy and safety
      profiles of atypical antipsychotic medications used for the adjunctive treatment
      of depression. METHODS AND FINDINGS: We included randomized trials comparing
      adjunctive antipsychotic medication to placebo for treatment-resistant depression
      in adults. Our literature search (conducted in December 2011 and updated on
      December 14, 2012) identified 14 short-term trials of aripiprazole,
      olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When
      possible, we supplemented published literature with data from manufacturers'
      clinical trial registries and US Food and Drug Administration New Drug
      Applications. Study duration ranged from 4 to 12 wk. All four drugs had
      statistically significant effects on remission, as follows: aripiprazole (odds
      ratio [OR], 2.01; 95% CI, 1.48-2.73), OFC (OR, 1.42; 95% CI, 1.01-2.0),
      quetiapine (OR, 1.79; 95% CI, 1.33-2.42), and risperidone (OR, 2.37; 95% CI, 1.31
      4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other
      drug. All drugs with the exception of OFC also had statistically significant
      effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58-2.72;
      NNT, 7), OFC (OR, 1.30, 95% CI, 0.87-1.93), quetiapine (OR, 1.53, 95% CI, 1.17
      2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16-2.88; NNT, 8). All four
      drugs showed statistically significant effects on clinician-rated depression
      severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69
      points on the Montgomery-Asberg Depression Rating Scale across drugs). On
      measures of functioning and quality of life, these medications produced either no
      benefit or a very small benefit, except for risperidone, which had a small-to
      moderate effect on quality of life (g = 0.49). Treatment was linked to several
      adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC,
      and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC),
      and weight gain (all four drugs, especially OFC). Shortcomings in study design
      and data reporting, as well as use of post hoc analyses, may have inflated the
      apparent benefits of treatment and reduced the apparent incidence of adverse
      events. CONCLUSIONS: Atypical antipsychotic medications for the adjunctive
      treatment of depression are efficacious in reducing observer-rated depressive
      symptoms, but clinicians should interpret these findings cautiously in light of
      (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to
      quality of life or functional impairment, and (3) the abundant evidence of
      potential treatment-related harm. Please see later in the article for the
      Editors' Summary.

PMID- 23554582
TI  - Large-scale neurochemical metabolomics analysis identifies multiple compounds
      associated with methamphetamine exposure.
AB  - Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative
      health consequences. The neurochemical effects of MA have been partially
      characterized, with a traditional focus on classical neurotransmitter systems.
      However, these directions have not yet led to novel drug treatments for MA abuse
      or toxicity. As an alternative approach, we describe here the first application
      of metabolomics to investigate the neurochemical consequences of MA exposure in
      the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures
      at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples
      were assayed using high-throughput gas and liquid chromatography mass
      spectrometry, yielding quantitative data on >300 unique metabolites. Association
      testing and false discovery rate control yielded several metabolome-wide
      significant associations with acute MA exposure, including compounds such as
      lactate (p = 4.4 * 10-5, q = 0.013), tryptophan (p = 7.0 * 10-4, q = 0.035) and 2
      hydroxyglutarate (p = 1.1 * 10-4, q = 0.022). Secondary analyses of MA-induced
      increase in locomotor activity showed associations with energy metabolites such
      as succinate (p = 3.8 * 10-7). Associations specific to repeated (5 day) MA
      exposure included phosphocholine (p = 4.0 * 10-4, q = 0.087) and ergothioneine (p
      = 3.0 * 10-4, q = 0.087). Our data appear to confirm and extend existing models
      of MA action in the brain, whereby an initial increase in energy metabolism,
      coupled with an increase in behavioral locomotion, gives way to disruption of
      mitochondria and phospholipid pathways and increased endogenous antioxidant
      response. Our study demonstrates the power of comprehensive MS-based metabolomics
      to identify drug-induced changes to brain metabolism and to develop neurochemical
      models of drug effects.

PMID- 23554584
TI  - Scaling Law for Cross-stream Diffusion in Microchannels under Combined
      Electroosmotic and Pressure Driven Flow.
AB  - This paper presents an analytical study of the cross-stream diffusion of an
      analyte in a rectangular microchannel under combined electroosmotic flow (EOF)
      and pressure driven flow to investigate the heterogeneous transport behavior and
      spatially-dependent diffusion scaling law. An analytical model capable of
      accurately describing 3D steady-state convection-diffusion in microchannels with
      arbitrary aspect ratios is developed based on the assumption of the thin Electric
      Double Layer (EDL). The model is verified against high-fidelity numerical
      simulation in terms of flow velocity and analyte concentration profiles with
      excellent agreement (<0.5% relative error). An extensive parametric analysis is
      then undertaken to interrogate the effect of the combined flow velocity field on
      the transport behavior in both the positive pressure gradient (PPG) and negative
      pressure gradient (NPG) cases. For the first time, the evolution from the spindle
      shaped concentration profile in the PPG case, via the stripe-shaped profile (pure
      EOF), and finally to the butterfly-shaped profile in the PPG case is obtained
      using the analytical model along with a quantitative depiction of the spatially
      dependent diffusion layer thickness and scaling law across a wide range of the
      parameter space.

PMID- 23554583
TI  - The influence of size, shape and vessel geometry on nanoparticle distribution.
AB  - Nanoparticles (NPs) are emerging as promising carrier platforms for targeted drug
      delivery and imaging probes. To evaluate the delivery efficiency, it is important
      to predict the distribution of NPs within blood vessels. NP size, shape and
      vessel geometry are believed to influence its biodistribution in circulation.
      Whereas, the effect of size on nanoparticle distribution has been extensively
      studied, little is known about the shape and vessel geometry effect. This paper
      describes a computational model for NP transport and distribution in a mimetic
      branched blood vessel using combined NP Brownian dynamics and continuum fluid
      mechanics approaches. The simulation results indicate that NPs with smaller size
      and rod shape have higher binding capabilities as a result of smaller drag force
      and larger contact area. The binding dynamics of rod-shaped NPs is found to be
      dependent on their initial contact points and orientations to the wall. Higher
      concentration of NPs is observed in the bifurcation area compared to the straight
      section of the branched vessel. Moreover, it is found that Peclet number plays an
      important role in determining the fraction of NPs deposited in the branched
      region and the straight section. Simulation results also indicate that NP binding
      decreases with increased shear rate. Dynamic NP re-distribution from low to high
      shear rates is observed due to the non-uniform shear stress distribution over the
      branched channel. This study would provide valuable information for NP
      distribution in a complex vascular network.

PMID- 23554585
TI  - Interstitial cells of Cajal, from structure to function.

PMID- 23554586
TI  - Imaging oxytocin * dopamine interactions: an epistasis effect of CD38 and COMT
      gene variants influences the impact of oxytocin on amygdala activation to social
      stimuli.
AB  - Although oxytocin (OT) has become a major target for the investigation of
      positive social processes, it can be assumed that it exerts its effects in
      concert with other neurotransmitters. One candidate for such an interaction is
      dopamine (DA). For both systems, genetic variants have been identified that
      influence the availability of the particular substance. A variant of the gene
      coding for the transmembrane protein CD38 (rs3796863), which is engaged in OT
      secretion, has been associated with OT plasma level. The common catechol-O
      methyltransferase (COMT) val158met polymorphism is known to influence COMT
      activity and therefore the degradation of DA. The present study aimed to
      investigate OT * DA interactions in the context of an OT challenge study. Hence,
      we tested the influence of the above mentioned genetic variants and their
      interaction on the activation of different brain regions (amygdala, VTA, ventral
      striatum and fusiform gyrus) during the presentation of social stimuli. In a
      pharmacological cross-over design 55 participants were investigated under OT and
      placebo (PLA) by means of fMRI. Brain imaging results revealed no significant
      effects for VTA or ventral striatum. Regarding the fusiform gyrus, we could not
      find any effects apart from those already described in Sauer et al. (2012).
      Analyses of amygdala activation resulted in no gene main effect, no gene *
      substance interaction but a significant gene * gene * substance interaction.
      While under PLA the effect of CD38 on bilateral amygdala activation to social
      stimuli was modulated by the COMT genotype, no such epistasis effect was found
      under OT. Our results provide evidence for an OT * DA interaction during
      responses to social stimuli. We postulate that the effect of central OT secretion
      on amygdala response is modulated by the availability of DA. Therefore, for an
      understanding of the effect of social hormones on social behavior, interactions
      of OT with other transmitter systems have to be taken into account.

PMID- 23554588
TI  - In vivo optogenetic tracing of functional corticocortical connections between
      motor forelimb areas.
AB  - Interactions between distinct motor cortical areas are essential for coordinated
      motor behaviors. In rodents, the motor cortical forelimb areas are divided into
      at least two distinct areas: the rostral forelimb area (RFA) and the caudal
      forelimb area (CFA). The RFA is thought to be an equivalent of the premotor
      cortex (PM) in primates, whereas the CFA is believed to be an equivalent of the
      primary motor cortex. Although reciprocal connections between the RFA and the CFA
      have been anatomically identified in rats, it is unknown whether there are
      functional connections between these areas that can induce postsynaptic spikes.
      In this study, we used an in vivo Channelrhodopsin-2 (ChR2) photostimulation
      method to trace the functional connections between the mouse RFA and CFA.
      Simultaneous electrical recordings were utilized to detect spiking activities
      induced by synaptic inputs originating from photostimulated areas. This method,
      in combination with anatomical tracing, demonstrated that the RFA receives strong
      functional projections from layer 2/3 and/or layer 5a, but not from layer 5b
      (L5b), of the CFA. Further, the CFA receives strong projections from L5b neurons
      of the RFA. The onset latency of electrical responses evoked in remote areas upon
      photostimulation of the other areas was approximately 10 ms, which is consistent
      with the synaptic connectivity between these areas. Our results suggest that
      neuronal activities in the RFA and the CFA during movements are formed through
      asymmetric reciprocal connections.

PMID- 23554589
TI  - Modeling heading and path perception from optic flow in the case of independently
      moving objects.
AB  - Humans are usually accurate when estimating heading or path from optic flow, even
      in the presence of independently moving objects (IMOs) in an otherwise rigid
      scene. To invoke significant biases in perceived heading, IMOs have to be large
      and obscure the focus of expansion (FOE) in the image plane, which is the point
      of approach. For the estimation of path during curvilinear self-motion no
      significant biases were found in the presence of IMOs. What makes humans robust
      in their estimation of heading or path using optic flow? We derive analytical
      models of optic flow for linear and curvilinear self-motion using geometric scene
      models. Heading biases of a linear least squares method, which builds upon these
      analytical models, are large, larger than those reported for humans. This
      motivated us to study segmentation cues that are available from optic flow. We
      derive models of accretion/deletion, expansion/contraction,
      acceleration/deceleration, local spatial curvature, and local temporal curvature,
      to be used as cues to segment an IMO from the background. Integrating these
      segmentation cues into our method of estimating heading or path now explains
      human psychophysical data and extends, as well as unifies, previous
      investigations. Our analysis suggests that various cues available from optic flow
      help to segment IMOs and, thus, make humans' heading and path perception robust
      in the presence of such IMOs.

PMID- 23554587
TI  - Cerebellar output in zebrafish: an analysis of spatial patterns and topography in
      eurydendroid cell projections.
AB  - The cerebellum is a brain region responsible for motor coordination and for
      refining motor programs. While a great deal is known about the structure and
      connectivity of the mammalian cerebellum, fundamental questions regarding its
      function in behavior remain unanswered. Recently, the zebrafish has emerged as a
      useful model organism for cerebellar studies, owing in part to the similarity in
      cerebellar circuits between zebrafish and mammals. While the cell types composing
      their cerebellar cortical circuits are generally conserved with mammals,
      zebrafish lack deep cerebellar nuclei, and instead a majority of cerebellar
      output comes from a single type of neuron: the eurydendroid cell. To describe
      spatial patterns of cerebellar output in zebrafish, we have used genetic
      techniques to label and trace eurydendroid cells individually and en masse. We
      have found that cerebellar output targets the thalamus and optic tectum, and have
      confirmed the presence of pre-synaptic terminals from eurydendroid cells in these
      structures using a synaptically targeted GFP. By observing individual
      eurydendroid cells, we have shown that different medial-lateral regions of the
      cerebellum have eurydendroid cells projecting to different targets. Finally, we
      found topographic organization in the connectivity between the cerebellum and the
      optic tectum, where more medial eurydendroid cells project to the rostral tectum
      while lateral cells project to the caudal tectum. These findings indicate that
      there is spatial logic underpinning cerebellar output in zebrafish with likely
      implications for cerebellar function.

PMID- 23554590
TI  - Top-down modulation of attention by emotion.

PMID- 23554591
TI  - An emerging paradigm: a strength-based approach to exploring mental imagery.
AB  - Mental imagery, or the ability to simulate in the mind information that is not
      currently perceived by the senses, has attracted considerable research interest
      in psychology since the early 1970's. Within the past two decades, research in
      this field-as in cognitive psychology more generally-has been dominated by
      neuroscientific methods that typically involve comparisons between imagery
      performance of participants from clinical populations with those who exhibit
      apparently normal cognitive functioning. Although this approach has been valuable
      in identifying key neural substrates of visual imagery, it has been less
      successful in understanding the possible mechanisms underlying another simulation
      process, namely, motor imagery or the mental rehearsal of actions without
      engaging in the actual movements involved. In order to address this oversight, a
      "strength-based" approach has been postulated which is concerned with
      understanding those on the high ability end of the imagery performance spectrum.
      Guided by the expert performance approach and principles of ecological validity,
      converging methods have the potential to enable imagery researchers to
      investigate the neural "signature" of elite performers, for example. Therefore,
      the purpose of this paper is to explain the origin, nature, and implications of
      the strength-based approach to mental imagery. Following a brief explanation of
      the background to this latter approach, we highlight some important theoretical
      advances yielded by recent research on mental practice, mental travel, and meta
      imagery processes in expert athletes and dancers. Next, we consider the
      methodological implications of using a strength-based approach to investigate
      imagery processes. The implications for the field of motor cognition are outlined
      and specific research questions, in dynamic imagery, imagery perspective,
      measurement, multi-sensory imagery, and metacognition that may benefit from this
      approach in the future are sketched briefly.

PMID- 23554592
TI  - From regular text to artistic writing and artworks: Fourier statistics of images
      with low and high aesthetic appeal.
AB  - The spatial characteristics of letters and their influence on readability and
      letter identification have been intensely studied during the last decades. There
      have been few studies, however, on statistical image properties that reflect more
      global aspects of text, for example properties that may relate to its aesthetic
      appeal. It has been shown that natural scenes and a large variety of visual
      artworks possess a scale-invariant Fourier power spectrum that falls off linearly
      with increasing frequency in log-log plots. We asked whether images of text share
      this property. As expected, the Fourier spectrum of images of regular typed or
      handwritten text is highly anisotropic, i.e., the spectral image properties in
      vertical, horizontal, and oblique orientations differ. Moreover, the spatial
      frequency spectra of text images are not scale-invariant in any direction. The
      decline is shallower in the low-frequency part of the spectrum for text than for
      aesthetic artworks, whereas, in the high-frequency part, it is steeper. These
      results indicate that, in general, images of regular text contain less global
      structure (low spatial frequencies) relative to fine detail (high spatial
      frequencies) than images of aesthetics artworks. Moreover, we studied images of
      text with artistic claim (ornate print and calligraphy) and ornamental art. For
      some measures, these images assume average values intermediate between regular
      text and aesthetic artworks. Finally, to answer the question of whether the
      statistical properties measured by us are universal amongst humans or are subject
      to intercultural differences, we compared images from three different cultural
      backgrounds (Western, East Asian, and Arabic). Results for different categories
      (regular text, aesthetic writing, ornamental art, and fine art) were similar
      across cultures.

PMID- 23554593
TI  - The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment
      (E-MCI).
AB  - OBJECTIVE: Our goal was to evaluate the association of APOE with amyloid
      deposition, cerebrospinal fluid levels (CSF) of Abeta, tau, and p-tau, brain
      atrophy, cognition and cognitive complaints in E-MCI patients and cognitively
      healthy older adults (HC) in the ADNI-2 cohort. METHODS: Two-hundred and nine E
      MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated
      the impact of diagnostic status (E-MCI vs. HC) and APOE epsilon4 status (epsilon4
      positive vs. epsilon4 negative) on cortical amyloid deposition (AV-45/Florbetapir
      SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based
      morphometry and Freesurfer version 5.1), CSF levels of Abeta, tau, and p-tau, and
      cognitive performance and complaints. RESULTS: E-MCI participants showed
      significantly impaired cognition, higher levels of cognitive complaints, greater
      levels of tau and p-tau, and subcortical and cortical atrophy relative to HC
      participants (p < 0.05). Cortical amyloid deposition and CSF levels of Abeta were
      significantly associated with APOE epsilon4 status but not E-MCI diagnosis, with
      epsilon4 positive participants showing more amyloid deposition and lower levels
      of CSF Abeta than epsilon4 negative participants. Other effects of APOE epsilon4
      status on cognition and CSF tau levels were also observed. CONCLUSIONS: APOE
      epsilon4 status is associated with amyloid accumulation and lower CSF Abeta, as
      well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC.
      Alternatively, neurodegeneration, cognitive impairment, and increased complaints
      are primarily associated with a diagnosis of E-MCI. These findings underscore the
      importance of considering APOE genotype when evaluating biomarkers in early
      stages of disease.

PMID- 23554594
TI  - Integrin activation States and eosinophil recruitment in asthma.
AB  - Eosinophil arrest and recruitment to the airway in asthma are mediated, at least
      in part, by integrins. Eosinophils express alpha4beta1, alpha6beta1, alphaLbeta2,
      alphaMbeta2, alphaXbeta2, alphaDbeta2, and alpha4beta7 integrins, which interact
      with counter-receptors on other cells or ligands in the extracellular matrix.
      Whether a given integrin-ligand pair mediates cell adhesion and migration depends
      on the activation state of the integrin. Integrins exist in an inactive bent, an
      intermediate-activity extended closed, and a high-activity extended open
      conformation. Integrin activation states can be monitored by conformation
      specific monoclonal antibodies (mAbs). Studies in mice indicate that both beta1
      and beta2 integrins mediate eosinophil recruitment to the lung. In vitro studies
      indicate that alpha4beta1 and alphaMbeta2 are the principal integrins mediating
      eosinophil adhesion, including to vascular cell adhesion molecule-1 and the novel
      alphaMbeta2 ligand periostin. In vivo, blood eosinophils have intermediate
      activity beta1 integrins, as judged by mAb N29, apparently resulting from
      eosinophil binding of P-selectin on the surface of activated platelets, and have
      a proportion of their beta2 integrins in the intermediate conformation, as judged
      by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5
      (IL-5). Airway eosinophils recovered by bronchoalveolar lavage (BAL) after
      segmental antigen challenge have high-activity beta1 integrins and high-activity
      alphaMbeta2 that does not require IL-5. Here we review information on how the
      activation states of eosinophil beta1 and beta2 integrins correlate with
      measurements of eosinophil recruitment and pulmonary function in asthma. Blood
      eosinophil N29 reactivity is associated with decreased lung function under
      various circumstances in non-severe asthma and KIM-127 with BAL eosinophil
      numbers, indicating that intermediate-activity alpha4beta1 and alphaMbeta2 of
      blood eosinophils are important for eosinophil arrest and consequently for
      recruitment and aspects of asthma.

PMID- 23554596
TI  - Recurrent Processing during Object Recognition.
AB  - How does the brain learn to recognize objects visually, and perform this
      difficult feat robustly in the face of many sources of ambiguity and variability?
      We present a computational model based on the biology of the relevant visual
      pathways that learns to reliably recognize 100 different object categories in the
      face of naturally occurring variability in location, rotation, size, and
      lighting. The model exhibits robustness to highly ambiguous, partially occluded
      inputs. Both the unified, biologically plausible learning mechanism and the
      robustness to occlusion derive from the role that recurrent connectivity and
      recurrent processing mechanisms play in the model. Furthermore, this interaction
      of recurrent connectivity and learning predicts that high-level visual
      representations should be shaped by error signals from nearby, associated brain
      areas over the course of visual learning. Consistent with this prediction, we
      show how semantic knowledge about object categories changes the nature of their
      learned visual representations, as well as how this representational shift
      supports the mapping between perceptual and conceptual knowledge. Altogether,
      these findings support the potential importance of ongoing recurrent processing
      throughout the brain's visual system and suggest ways in which object recognition
      can be understood in terms of interactions within and between processes over
      time.

PMID- 23554595
TI  - Molecular mechanisms of peripheral nerve regeneration: emerging roles of
      microRNAs.
AB  - MicroRNAs are small non-coding RNAs that suppress gene expression through target
      mRNA degradation or translation repression. Recent studies suggest that miRNA
      plays an important role in multiple physiological and pathological processes in
      the nervous system. In this review article, we described what is currently known
      about the mechanisms in peripheral nerve regeneration on cellular and molecular
      levels. Recently, changes in microRNA expression profiles have been detected in
      different injury models, and emerging evidence strongly indicates that these
      changes promote neurons to survive by shifting their physiology from maintaining
      structure and supporting synaptic transmission towards a regenerative phenotype.
      We reviewed the putative mechanisms involved in miRNA mediated post
      transcriptional regulation and pointed out several areas where future research is
      necessary to advance our understanding of how targeting miRNA machinery can be
      used as a therapeutic approach for treating nerve injuries.

PMID- 23554597
TI  - Perceived and actual social discrimination: the case of overweight and social
      inclusion.
AB  - The present study examined the correspondence between perceived and actual social
      discrimination of overweight people. In total, 77 first-year students provided
      self-ratings about their height, weight, and perceived social inclusion. To
      capture actual social inclusion, each participant nominated those fellow students
      (a) she/he likes and dislikes and (b) about whom she/he is likely to hear social
      news. Students with lower Body Mass Index (BMI) felt socially included,
      irrespective of their actual social inclusion. In contrast, students with higher
      BMI felt socially included depending on the degree of their actual social
      inclusion. Specifically, their felt social inclusion accurately reflected whether
      they were actually liked/disliked, but only when they were part of social news.
      When not part of social news, they also showed insensitivity to their actual
      social inclusion status. Thus, students with a lower BMI tended to be
      insensitive, while students with a higher BMI showed a differential sensitivity
      to actual social discrimination.

PMID- 23554598
TI  - Constraints on the transfer of perceptual learning in accented speech.
AB  - The perception of speech sounds can be re-tuned through a mechanism of lexically
      driven perceptual learning after exposure to instances of atypical speech
      production. This study asked whether this re-tuning is sensitive to the position
      of the atypical sound within the word. We investigated perceptual learning using
      English voiced stop consonants, which are commonly devoiced in word-final
      position by Dutch learners of English. After exposure to a Dutch learner's
      productions of devoiced stops in word-final position (but not in any other
      positions), British English (BE) listeners showed evidence of perceptual learning
      in a subsequent cross-modal priming task, where auditory primes with devoiced
      final stops (e.g., "seed", pronounced [si:t(h)]), facilitated recognition of
      visual targets with voiced final stops (e.g., SEED). In Experiment 1, this
      learning effect generalized to test pairs where the critical contrast was in word
      initial position, e.g., auditory primes such as "town" facilitated recognition of
      visual targets like DOWN. Control listeners, who had not heard any stops by the
      speaker during exposure, showed no learning effects. The generalization to word
      initial position did not occur when participants had also heard correctly voiced,
      word-initial stops during exposure (Experiment 2), and when the speaker was a
      native BE speaker who mimicked the word-final devoicing (Experiment 3). The
      readiness of the perceptual system to generalize a previously learned adjustment
      to other positions within the word thus appears to be modulated by distributional
      properties of the speech input, as well as by the perceived sociophonetic
      characteristics of the speaker. The results suggest that the transfer of pre
      lexical perceptual adjustments that occur through lexically driven learning can
      be affected by a combination of acoustic, phonological, and sociophonetic
      factors.

PMID- 23554600
TI  - When a Stone Tries to Climb up a Slope: The Interplay between Lexical and
      Perceptual Animacy in Referential Choices.
AB  - Several studies suggest that referential choices are influenced by animacy. On
      the one hand, animate referents are more likely to be mentioned as subjects than
      inanimate referents. On the other hand, animate referents are more frequently
      pronominalized than inanimate referents. These effects have been analyzed as
      effects of conceptual accessibility. In this paper, we raise the question whether
      these effects are driven only by lexical concepts, such that referents described
      by animate lexical items (e.g., "toddler") are more accessible than referents
      described by inanimate lexical items (e.g., "shoe"), or can also be influenced by
      context-derived conceptualizations, such that referents that are perceived as
      animate in a particular context are more accessible than referents that are not.
      In two animation-retelling experiments, conducted in Dutch, we investigated the
      influence of lexical and perceptual animacy on the choice of referent and the
      choice of referring expression. If the effects of animacy are context-dependent,
      entities that are perceived as animate should yield more subject references and
      more pronouns than entities that are perceived as inanimate, irrespective of
      their lexical animacy. If the effects are tied to lexical concepts, entities
      described with animate lexical items should be mentioned as the subject and
      pronominalized more frequently than entities described with inanimate lexical
      items, irrespective of their perceptual animacy. The results show that while only
      lexical animacy appears to affect the choice of subject referent, perceptual
      animacy may overrule lexical animacy in the choice of referring expression. These
      findings suggest that referential choices can be influenced by conceptualizations
      based on the perceptual context.

PMID- 23554599
TI  - Remembering new words: integrating early memory development into word learning.
AB  - In order to successfully acquire a new word, young children must learn the
      correct associations between labels and their referents. For decades, word
      learning researchers have explored how young children are able to form these
      associations. However, in addition to learning label-referent mappings, children
      must also remember them. Despite the importance of memory processes in forming a
      stable lexicon, there has been little integration of early memory research into
      the study of early word learning. After discussing what we know about how young
      children remember words over time, this paper reviews the infant memory
      development literature as it relates to early word learning, focusing on changes
      in retention duration, encoding, consolidation, and retrieval across the first 2
      years of life. A third section applies this review to word learning and presents
      future directions, arguing that the integration of memory processes into the
      study of word learning will provide researchers with novel, useful insights into
      how young children acquire new words.

PMID- 23554601
TI  - In vivo activation of methyl-coenzyme M reductase by carbon monoxide.
AB  - Methyl-coenzyme M reductase (MCR) from methanogenic archaea catalyzes the rate
      limiting and final step in methane biosynthesis. Using coenzyme B as the two
      electron donor, MCR reduces methyl-coenzyme M (CH3-SCoM) to methane and the mixed
      disulfide, CoBS-SCoM. MCR contains an essential redox-active nickel
      tetrahydrocorphinoid cofactor, Coenzyme F430, at its active site. The active form
      of the enzyme (MCRred1) contains Ni(I)-F430. Rapid and efficient conversion of
      MCR to MCRred1 is important for elucidating the enzymatic mechanism, yet this
      reduction is difficult because the Ni(I) state is subject to oxidative
      inactivation. Furthermore, no in vitro methods have yet been described to convert
      Ni(II) forms into MCRred1. Since 1991, it has been known that MCRred1 from
      Methanothermobacter marburgensis can be generated in vivo when cells are purged
      with 100% H2. Here we show that purging cells or cell extracts with CO can also
      activate MCR. The rate of in vivo activation by CO is about 15 times faster than
      by H2 (130 and 8 min(-1), respectively) and CO leads to twofold higher MCRred1
      than H2. Unlike H2-dependent activation, which exhibits a 10-h lag time, there is
      no lag for CO-dependent activation. Based on cyanide inhibition experiments,
      carbon monoxide dehydrogenase is required for the CO-dependent activation.
      Formate, which also is a strong reductant, cannot activate MCR in M. marburgensis
      in vivo.

PMID- 23554602
TI  - Catalyzing plant science research with RNA-seq.
AB  - Next generation DNA sequencing technologies are driving increasingly rapid,
      affordable and high resolution analyses of plant transcriptomes through
      sequencing of their associated cDNA (complementary DNA) populations; an
      analytical platform commonly referred to as RNA-sequencing (RNA-seq). Since
      entering the arena of whole genome profiling technologies only a few years ago,
      RNA-seq has proven itself to be a powerful tool with a remarkably diverse range
      of applications, from detailed studies of biological processes at the cell type
      specific level, to providing insights into fundamental questions in plant biology
      on an evolutionary time scale. Applications include generating genomic data for
      heretofore unsequenced species, thus expanding the boundaries of what had been
      considered "model organisms," elucidating structural and regulatory gene
      networks, revealing how plants respond to developmental cues and their
      environment, allowing a better understanding of the relationships between genes
      and their products, and uniting the "omics" fields of transcriptomics,
      proteomics, and metabolomics into a now common systems biology paradigm. We
      provide an overview of the breadth of such studies and summarize the range of RNA
      seq protocols that have been developed to address questions spanning cell type
      specific-based transcriptomics, transcript secondary structure and gene mapping.

PMID- 23554605
TI  - Intrinsic control of axon regeneration.
AB  - Spinal cord injury disrupts the connections between the brain and spinal cord,
      often resulting in the loss of sensory and motor function below the lesion site.
      The most important reason for such permanent functional deficits is the failure
      of injured axons to regenerate after injury. In principle, the functional
      recovery could be achieved by two forms of axonal regrowth: the regeneration of
      lesioned axons which will reconnect with their original targets and the sprouting
      of spared axons that form new circuits and compensate for the lost function. Our
      recent studies reveal the activity of the mammalian target of rapamycin (mTOR)
      pathway, a major regulator of new protein synthesis, as a critical determinant of
      axon regrowth in the adult retinal ganglion neurons[1]. In this review, I
      summarize current understanding of the cellular and molecular mechanisms that
      control the intrinsic regenerative ability of mature neurons.

PMID- 23554604
TI  - Reading, writing, and repair: the role of ubiquitin and the ubiquitin-like
      proteins in DNA damage signaling and repair.
AB  - Genomic instability is both a hallmark of cancer and a major contributing factor
      to tumor development. Central to the maintenance of genome stability is the
      repair of DNA damage, and the most toxic form of DNA damage is the DNA double
      strand break. As a consequence the eukaryotic cell harbors an impressive array of
      protein machinery to detect and repair DNA breaks through the initiation of a
      multi-branched, highly coordinated signaling cascade. This signaling cascade,
      known as the DNA damage response (DDR), functions to integrate DNA repair with a
      host of cellular processes including cell cycle checkpoint activation,
      transcriptional regulation, and programmed cell death. In eukaryotes, DNA is
      packaged in chromatin, which provides a mechanism to regulate DNA transactions
      including DNA repair through an equally impressive array of post-translational
      modifications to proteins within chromatin, and the DDR machinery itself.
      Histones, as the major protein component of chromatin, are subject to a host of
      post-translational modifications including phosphorylation, methylation, and
      acetylation. More recently, modification of both the histones and DDR machinery
      by ubiquitin and other ubiquitin-like proteins, such as the small ubiquitin-like
      modifiers, has been shown to play a central role in coordinating the DDR. In this
      review, we explore how ubiquitination and sumoylation contribute to the "writing"
      of key post-translational modifications within chromatin that are in turn "read"
      by the DDR machinery and chromatin-remodeling factors, which act together to
      facilitate the efficient detection and repair of DNA damage.

PMID- 23554608
TI  - The preparation and characterization of folate-conjugated human serum albumin
      magnetic cisplatin nanoparticles.
AB  - OBJECTIVE: Nanoparticles are becoming an important method of targeted drug
      delivery. To evaluate the importance of folate-conjugated human serum albumin
      (HSA) magnetic nanoparticles (Folate-CDDP/HSA MNP), we prepared drug-loaded
      Folate-CDDP/HSA MNPs and characterized their features. METHODS: First, folate was
      conjugated with HSA under the effect of a condensing agent, and the conjugating
      rate was evaluated by a colorimetric method using 2, 4, 6 - trinitrobenzene
      sulfonic acid. Second, under N2 gas, Fe3O4 magnetic nanomaterials were prepared
      and characterized by using transmission electron microscopy (TEM), SEM-EDS and X
      ray diffraction (XRD). Finally, Folate-CDDP/HSA MNP was prepared by using a
      solvent evaporation technique. TEM was used to observe particle morphology. The
      particle size and distribution of the prepared complexes were determined by a
      Laser particle size analyzer. Drug loading volume and drug release were
      investigated by a high performance liquid chromatography method (HPLC) in vitro.
      RESULTS: We successfully prepared folate-conjugated HSA and its conjugating rate
      was 27.26 ug/mg. Under TEM, Fe3O4 magnetic nanoparticles were highly electron
      density and had an even size distribution in the range of 10-20 nm. It was
      confirmed by SEM-EDS and XRD that Fe3O4 magnetic nanoparticles had been
      successfully prepared. Under TEM, drug-loaded magnetic nanoparticles were
      observed, which had a round shape, similar uniform size and smooth surface. Their
      average size was 79 nm which was determined by laser scattering, and they
      exhibited magnetic responsiveness. Encapsulation efficiency was 89.75% and
      effective drug loading was calculated to be 15.25%. The release results in vitro
      showed that the half release time (t1/2) of cisplatin in cisplatin Solution and
      Folate-CDDP/HSA MNP was 65 min and 24 h respectively, which indicated that
      microspheres had an obvious effect of sustained-release. CONCLUSION: Folate
      CDDP/HSA MNPs were prepared successfully. The preparation process and related
      characteristics data provided a foundation for further study, including the
      mechanism of the nanoparticles distribution in vivo and their intake by tumor
      cells.

PMID- 23554606
TI  - Emerging roles of cardiolipin remodeling in mitochondrial dysfunction associated
      with diabetes, obesity, and cardiovascular diseases.
AB  - Cardiolipin (CL) is a phospholipid exclusively localized in inner mitochondrial
      membrane where it is required for oxidative phosphorylation, ATP synthesis, and
      mitochondrial bioenergetics. The biological functions of CL are thought to depend
      on its acyl chain composition which is dominated by linoleic acids in
      metabolically active tissues. This unique feature is not derived from the de novo
      biosynthesis of CL, rather from a remodeling process that involves in
      phospholipases and transacylase/acyltransferase. The remodeling process is also
      believed to be responsible for generation of CL species that causes oxidative
      stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages
      by reactive oxygen species (ROS) due to its high content in polyunsaturated fatty
      acids and location near the site of ROS production. Consequently, pathological
      remodeling of CL has been implicated in the etiology of mitochondrial dysfunction
      commonly associated with diabetes, obesity, heart failure, neurodegeneration, and
      aging that are characterized by oxidative stress, CL deficiency, and abnormal CL
      species. This review summarizes recent progresses in molecular, enzymatic,
      lipidomic, and metabolic studies that support a critical regulatory role of
      pathological CL remodeling as a missing link between oxidative stress and
      mitochondrial dysfunction in metabolic diseases and aging.

PMID- 23554609
TI  - Prediction of candidate small non-coding RNAs in Agrobacterium by computational
      analysis.
AB  - Small non-coding RNAs with important regulatory roles are not confined to
      eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs
      (sRNAs), some of which have been shown to regulate critical cellular processes.
      Computational approaches, in combination with molecular experiments, have played
      an important role in the identification of these sRNAs. At present, there is no
      information on the presence of small non-coding RNAs and their genes in the
      Agrobacterium tumefaciens genome. To identify potential sRNAs in this important
      bacterium, deep sequencing of the short RNA populations isolated from
      Agrobacterium tumefaciens C58 was carried out. From a data set of more than
      10,000 short sequences, 16 candidate sRNAs have been tentatively identified based
      on computational analysis. All of these candidates can form stem-loop structures
      by RNA folding predictions and the majority of the secondary structures are rich
      in GC base pairs. Some are followed by a short stretch of U residues, indicative
      of a rho-independent transcription terminator, whereas some of the short RNAs are
      found in the stem region of the hairpin, indicative of eukaryotic-like sRNAs.
      Experimental strategies will need to be used to verify these candidates. The
      study of an expanded list of candidate sRNAs in Agrobacterium will allow a more
      complete understanding of the range of roles played by regulatory RNAs in
      prokaryotes.

PMID- 23554607
TI  - A review of adjuvants for Leishmania vaccine candidates.
AB  - Over the last decade, there has been a flurry of research on adjuvants for
      vaccines, and several novel adjuvants are now licensed products or in late stage
      clinical development. The success of adjuvants in enhancing the immune response
      to antigens has led many researchers to re-focus their vaccine development
      programs. Although several vaccine candidates have been tested against
      leishmaniasis, there is yet no effective vaccine against this parasitic disease.
      Recent research has documented that efforts to develop effective Leishmania
      vaccine have been limited due to lack of an appropriate adjuvant. In view of
      this, this review paper outlines some of the adjuvants that have been used in
      Leishmania vaccine candidates and cites a few of the responses obtained from
      these studies. The aim of the present review is to consolidate these findings to
      facilitate the application of these adjuvants in general and experimental
      vaccinology.

PMID- 23554611
TI  - The potential of carcinoembryonic antigen, p53, Ki-67 and glutathion Stransferase
      pi as clinico-histopathological markers for colorectal cancer.
AB  - OBJECTIVE: Colorectal cancer is one of the major contributors to cancer death
      worldwide. Lack of reliable colorectal cancer markers has hampered the management
      of these cancer patients. Our main purpose was to study the correlation between
      histopathological variables of colorectal adenocarcinomas and identify
      histopathological markers that are of prognostic value in patients with
      colorectal cancer. METHODS: In the present study, we examined the expression of
      carcinoembryonic antigen (CEA), p53, Ki-67 and glutathion Stransferase (GST) -pi
      by using immunohistochemical staining methods in 126 colorectal carcinoma
      patients and evaluated the lymph node metastasis status in these patients by
      histopathological examination. RESULTS: The positive rates of CEA, p53, Ki-67 and
      GST-pi expression in the colorectal cancer tissue specimens examined were 95.23%,
      55.56%, 53.38% and 82.30%, respectively. Expression of p53 and Ki-67 was
      significantly correlated with the Dukes stages of the tumor, with higher levels
      of these proteins in Dukes'C and D tumors than those in Dukes' A and B tumors.
      Furthermore, the expression of p53, GST-pi and Ki-67 correlated with prognosis of
      patients with colorectal cancer. Additionally, the expression of p53 in
      colorectal cancer was closely related to the expression of Ki-67 and the
      expression of GST-pi was directly correlated with that of p53. CONCLUSION: The
      expression of CEA, p53, Ki-67 and GST-pi was correlated with various clinical
      features of patients with colorectal cancer. The combined use of these
      histopathological markers appeared to be a promising tool in predicting the
      prognosis of patients with this type of cancer.

PMID- 23554610
TI  - The remedial effect of soluble interleukin-1 receptor type II on endometriosis in
      the nude mouse model.
AB  - OBJECTIVE: Recent studies have shown that the local expression of soluble
      interleukin (IL) -1 receptor type II (sIL-1 RII) in endometrial tissue of women
      with endometriosis is decreased, and the depression of IL-1 RII was more
      significant in infertile women than that in fertile women with endometriosis. In
      this research, we investigated the remedial effect of sIL-1-RII administration on
      endometriosis in the nude mouse model. METHODS: NINETEEN NUDE MODEL MICE WITH
      ENDOMETRIOSIS WERE RANDOMLY DIVIDED INTO THREE GROUPS: group A was treated by
      intraperitoneal administration with only sIL-1 RII for two weeks, group B was
      similarly treated with only IL-1, and group C (control) was administered saline .
      After 2 weeks, the size of the ectopic endometrial lesions was calculated, and
      the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma
      leukemia-2 (Bcl-2) were detected by immunohistochemistry. The IL-8 and VEGF
      levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The mean size of ectopic endometrial lesion
      did not differ between the three groups (P > 0.05). Compared with the control,
      the expression of VEGF and Bcl-2 was significantly lower in group A, and higher
      in group B. In the three groups, the levels of IL-8 in the PF and serum were
      highest in group A, and lowest in group B. CONCLUSION: sIL-1 RII may suppresse
      hyperplasia of ectopic endometriosis, perhaps by reducing the expression of
      certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new
      clinical strategy for the treatment of endometriosis.

PMID- 23554612
TI  - Construction and identification of recombinant lentiviral vector containing HIV-1
      Tat gene and its expression in 293T cells.
AB  - OBJECTIVE: To construct a lentiviral vector expressing HIV-1 Tat and identify its
      expression in 293T cells. METHODS: The gene fragment of HIV-1 Tat101 was
      subcloned to lentiviral transfer vector pHAGE-CMV-MCS-IZsGreen, which was named
      pHAGE-Tat. Then the constructed pHAGE-Tat was used to co-transfect the packing
      293T cells, together with the packaging plasmids pMD2.G and psPAX2. The packaged
      viral particles designated LV-Tat were used to infect the 293T cells and the
      viral titer was calculated. The expression of HIV-1 Tat in 293T cells was
      confirmed using RT-PCR and western blot. RESULTS: The recombinant lentiviral
      vector was successfully constructed and could express HIV-1 Tat in 293T cells.
      The virus titer was 5.73*10(6) ifu/ml. CONCLUSION: The successfully constructed
      recombinant lentiviral vector makes a strong foundation for further exploring the
      possible role of HIV-1 Tat in the development of prostate cancer.

PMID- 23554613
TI  - Reduction of G0 phase cells of colon cancer caco-2 cells may enhance 5
      fluorouracil efficacy.
AB  - OBJECTIVE: A major problem in the chemotherapy of colon caner may be due to those
      cells that are in residence in the G0 phase where they are less vulnerable to
      conventional therapy. To overcome this phenomenon, we attempted to recruit the
      reentry of these cells into the cell cycle via a signaling pathway that
      manipulates tumor growth. METHODS: Epidermal growth factor (EGF) was used to
      stimulate colon cancer caco-2 cells. FACS analysis and proliferating cell nuclear
      antigen (PCNA) staining were used to estimate the cell cycle transition and cell
      proliferation activated by EGF, and a MTT assay was used to evaluate the
      synergistic effect of EGF and chemotherapy. RESULTS: The percentage of caco-2
      cells in the G0/G1 phase was significantly reduced by nearly 20% and the
      percentages in the S and G2/M phases were increased by EGF. The combined use of
      EGF and 5-fluorouracil (5-FU) enhanced the caco-2 cell chemosensitivity to 5-FU,
      reaching a maximum of an approximately threefold greater sensitivity than to 5-FU
      alone as judged by the 50% inhibiting concentration (IC50). CONCLUSION: Our study
      demonstrated that stimulation by EGF enhanced the chemosensitivity of caco-2
      cells to 5-FU, which may be a novel therapeutic protocol in colon cancer.

PMID- 23554614
TI  - Left ventricular hypertrophy amplifies the QT, and Tp-e intervals and the Tp-e/
      QT ratio of left chest ECG.
AB  - OBJECTIVE: To evaluate the changes in Tp-e interval (an interval from the peak to
      the end of the T wave), QT interval and Tp-e/QT ratio of the body surface ECG in
      patients with left ventricular hypertrophy (LVH). METHODS: The Tp-e interval and
      QT interval were measured on body surface ECGs in 42 patients without either
      hypertension or LVH (control group), 41 patients having hypertension but not LVH
      (non-LVH group), and 38 patients with both hypertension and LVH (LVH group).
      RESULTS: The mean corrected QT (QTc) interval, and mean corrected Tp-e[T(p-e)c]
      interval were significantly longer in the LVH group (0.430+/-0.021s vs. 0.409+/
      0.019s, p < 0.01; 0.098+/-0.013s vs. 0.088+/-0.011s, respectively) than those in
      the control group. The Tp-e/QT ratio was also amplified in LVH group (0.232+/
      0.028 vs.0.218+/-0.027) (p < 0.05). CONCLUSION: LVH increased the QT interval, Tp
      e interval and Tp-e/QT ratio of the body surface ECG.

PMID- 23554615
TI  - Clinical results of tricuspid valve replacement - a 21-case report.
AB  - OBJECTIVE: To summarize the clinical experiences of 21 patients treated with
      tricuspid valve replacement (TVR) and investigate the surgical indications and
      methods. METHODS: Data from 21 patients who underwent TVR from December 2002 to
      March 2009 were retrospectively collected and analyzed. The mean age was 48.86+/
      15.37 years (range: 20-72 years). The underlying disease of the patients was
      classified as rheumatic (n = 10), congenital (n = 8), endocarditis (n = 2) or
      chest trauma (n = 1). Previous cardiac surgery had been performed in 12 patients
      (57.14%). RESULTS: In-hospital death occurred in two patients (9.52%).
      Postoperative morbidities included cardiac failure (n = 2), bleeding related re
      operation (n = 1), and plural effusion (n = 2). CONCLUSION: The early outcomes of
      TVR were acceptable. At the present time TVR can be performed through optimal
      perioperative management.

PMID- 23554616
TI  - Coronary artery bypass grafting with concomitant resection for carcinoma of lung.
AB  - A 69-year-old woman with angina had a lesion in the left lower lobe on chest
      film. Angiography revealed coronary artery disease in three vessels. Combined off
      pump coronary artery bypass grafting (CABG) and left lower lobectomy were
      performed through median sternotomy. This approach avoids complications due to
      staged operations and cardiopulmonary bypass (CPB). This report shows that
      simultaneous off pump CABG and pulmonary operations can be performed safely in
      patients with coronary artery disease (CAD) associated with lung cancer.

PMID- 23554617
TI  - Tinea incognito due to microsporum gypseum.
AB  - A 41-year-old woman presented with a pruritic rash on the face that was of 3
      months duration. During that time, it had been successively misdiagnosed as
      psoriasis vulgaris, systemic lupus erythematosus, facial dermatitis at other
      hospitals, and had been treated with agents that included acitretin and
      prednisone. Finally, fungi were found in the lesions by optical microscopy, and
      the fungal culture was positive for Microsporum gypseum, and was diagnosed as a
      Microsporum gypseum infection. The lesions eventually cleared completely after 8
      weeks of antifungal treatment.

PMID- 23554619
TI  - A 5'-flanking region polymorphism in toll-like receptor 4 is associated with
      gastric cancer in a Chinese population.
AB  - OBJECTIVE: Inflammation induced by H.pylori colonization in the stomach is
      related to the development of gastric cancer and the genetic variations of the
      genes involved in the immune responses modify the host response to the infection.
      The aim of this study was to evaluate whether polymorphisms in the toll-like
      receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity,
      were related to the susceptibility to gastric cancer in a Chinese population.
      METHODS: Two variations in the 5'-flanking region of TLR4 (rs1927914 T > C and
      rs10759932 T > C) were genotyped by using the PCR-restriction fragment length
      polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric
      cancer cases and 1,100 cancer-free controls in a Chinese population. RESULTS:
      Individuals carrying the C allele of rs10759932 had a significantly reduced risk
      of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild
      type homozygote (TT), and the protective effect was not significantly different
      among subgroups stratified by age, sex, smoking, drinking and H.pylori infection
      status (P for heterogeneity > 0.05). No significant association was observed
      between rs1927914 and gastric cancer risk in this study population. CONCLUSION:
      The T to C allele substitution of rs10759932 may play a protective role in
      gastric carcinogenesis in a Chinese population. Large studies with different
      ethnic populations are warranted to confirm these findings.

PMID- 23554620
TI  - An Implanted Closed-loop Chip System for Heart Rate Control: System Design and
      Effects in Conscious Rats.
AB  - OBJECTIVE: To evaluate the efficiency of an implanted chip system for the control
      of heart rate (HR). METHODS: The HR was recorded in six conscious Sprague-Dawley
      (SD) rats. An implanted chip system was designed to regulate the HR by
      stimulating the right cervical vagus nerve according to the feedback of real time
      HR. Each rat was subjected to 30-min regulation and 30-min recovery. The change
      of HR during the regulation period was compared with the control. The ECG was
      recorded during the experiment for 24 h. RESULTS: The ECG signals were
      successfully recorded during the experiment. The HR was significantly decreased
      during the period of regulation compared with control (-79.3 +/-34.5, P < 0.01, n
      = 6) and then recovered to normal after regulation. CONCLUSION: The described
      implanted chip system can regulate the HR to a designated set point.

PMID- 23554618
TI  - Down syndrome and the molecular pathogenesis resulting from trisomy of human
      chromosome 21.
AB  - Chromosome copy number aberrations, anueploidies, are common in the human
      population but generally lethal. However, trisomy of human chromosome 21 is
      compatible with life and people born with this form of aneuploidy manifest the
      features of Down syndrome, named after Langdon Down who was a 19(th) century
      British physician who first described a group of people with this disorder. Down
      syndrome includes learning and memory deficits in all cases, as well as many
      other features which vary in penetrance and expressivity in different people.
      While Down syndrome clearly has a genetic cause - the extra dose of genes on
      chromosome 21 - we do not know which genes are important for which aspects of the
      syndrome, which biochemical pathways are disrupted, or, generally how design
      therapies to ameliorate the effects of these disruptions. Recently, with new
      insights gained from studying mouse models of Down syndrome, specific genes and
      pathways are being shown to be involved in the pathogenesis of the disorder. This
      is opening the way for exciting new studies of potential therapeutics for aspects
      of Down syndrome, particularly the learning and memory deficits.

PMID- 23554621
TI  - The effects of a new shape-memory alloy interspinous process device on the
      distribution of intervertebral disc pressures in vitro.
AB  - This study was designed to measure the pressure distribution of the
      intervertebral disc under different degrees of distraction of the interspinous
      process, because of a suspicion that the degree of distraction of the spinous
      process may have a close relationship with the disc load share. Six human cadaver
      lumbar spine L2-L5 segments were loaded in flexion, neutral position, and
      extension. The L3-L4 disc load was measured at each position using pressure
      measuring films. Shape-memory interspinous process implants (SMID) with different
      spacer heights, ranging in size from 10 to 20 mm at 2 mm increments, were used.
      It was found that a SMID with a spacer height equal to the distance of the
      interspinous process in the neutral position can share the biomechanical disc
      load without a significant change of load in the anterior annulus. An
      interspinous process stabilizing device (IPD) would not be appropriate to use in
      those cases with serious spinal stenosis because the over-distraction of the
      interspinous process by the SMID would lead to overloading the anterior annulus
      which is a recognized cause of disc degeneration.

PMID- 23554622
TI  - The relationship between the expression of tumor matrix-metalloproteinase and the
      characteristics of magnetic resonance imaging of human gliomas.
AB  - OBJECTIVE: To investigate the relationship between the expression level of matrix
      metalloproteinases (MMPs) with the pathological grades and MRI characteristics of
      human gliomas. METHODS: Prior pre- and post-contrast enhancement MRI was
      performed on 31 patients with gliomas, which were confirmed by post-operational
      pathology. The expression of MMP-2 and MMP-9 were determined by
      immunohistochemical staining in both a low grading group (grades I and II, n =
      20) and high grading group (grades III and IV, n = 11). RESULTS: Compared to the
      low grading group, the expression levels of MMP-2, MMP-9, as well as the tumor
      edema index (EI), enhanced percentage (EP) and maximum diameters were
      significantly greater in the high grading group. MMP-2 and MMP-9 expression were
      correlated with the tumor EI, EP and the maximum diameters. There were no
      differences in MMP-2 and MMP-9 expression between the unclear border definition
      group and the clear border definition group, whereas the MMPs expression levels
      were greater in the heterogeneous signal group than in the homogeneous signal
      group. CONCLUSION: The expression level of MMPs is correlated with the invasion
      ability of human gliomas. The MRI parameters, such as tumor EI, EP, maximum
      diameter, and signal heterogeneity technically reflect the expression level of
      MMPs, and can be used to estimate the tumor's malignant behavior, thus providing
      the guidance for clinical therapies.

PMID- 23554623
TI  - Ceramide from sphingomyelin hydrolysis differentially mediates mitogen-activated
      protein kinases (MAPKs) activation following cerebral ischemia in rat hippocampal
      CA1 subregion.
AB  - OBJECTIVE: To explore the role that ceramide plays in the activation of mitogen
      activated protein kinases (MAPKs) during cerebral ischemia and reperfusion.
      METHODS: Rats were subjected to ischemia by the four-vessel occlusion (4-VO)
      method. The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion
      of the rat hippocampus before inducing ischemia. Western blot was used to examine
      the activity of extracellular-signal regulated kinase (ERK) and c-Jun N-terminal
      protein kinase (JNK) using antibodies against ERK, JNK and diphosphorylated ERK
      and JNK. RESULTS: At 1h reperfusion post-ischemia, JNK reached its peak activity
      while ERK was undergoing a sharp inactivation (P < 0.05). The level of
      diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK
      was visibly reversed (P < 0.05) by the sphingomyelinase inhibitor. CONCLUSION:
      The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis
      in brain ischemia, promoting JNK activation and suppressing ERK activation,
      culminating in the ischemic lesion.

PMID- 23554624
TI  - The protective effect of 17 beta-estradiol on oxygen-induced retinopathy and its
      relation with the changes of malondialdehyde.
AB  - OBJECTIVE: Retinopathy of prematurity is becoming obvious with the improvement of
      neonatal ambulance. However there is still not a good treatment. The present
      study is to observe the effect of 17 beta-estradiol (E2) on oxygen-induced
      retinopathy (OIR), and explore the relationship between the changes of avascular
      area and malondialdehyde (MDA) in retina. METHODS: Newborn oxygen-exposed mice
      underwent subcutaneous injections of different dose of E2 (0.1 ug, 1.0 ug, 10.0
      ug ), tamoxifen or phosphate buffered saline (PBS; controls)everyday from post
      natal day (p)7 to p17. At p17, retinal flat mounts were scored for the percentage
      of avascular/total retinal area, and pathological changes during
      revascularization. The MDA concentration in the retina was determined also. In
      the most efficacious E2 group (10.0 ug), 100.0 ug tamoxifen was also
      administered, and the percentage of capillary-free/total retinal area determined,
      and the retinal malondialdehyde concentration assayed. RESULTS: The mean
      percentage of capillary-free area over total retinal area was 0(PBS, in room
      air), 34.197+/-1.301(PBS, in hyperoxia), 23.685+/-0.407 (0.1 ug E2), 14.648+/
      0.355 (1.0 ug E2), 4.693+/-0.450 (10.0 ug E2) and 32.240+/-0.654 (10.0 ug E2
      +100.0 ug tamoxifen). The difference was significant (F = 2778.759, P < 0.01),
      and the difference between any two groups were also significant (all P value were
      less than 0.01). The predilection of tufts and clusters during revascularization
      was mainly aggregated in zones 2 and 3, but the difference of retinal neovascular
      clusters and tufts in fourth zone among different groups were significant
      [clusters (F = 44.719, P < 0.01) vs tufts (F = 39.997, P < 0.01)]. The mean MDA
      concentration were 0.711+/-0.037(PBS, in room air), 2.084+/-0.066 (PBS, in
      hyperoxia), 1.829+/-0.091(0.1 ug E2), 1.152+/-0.067(1.0 ug E2), 0.796+/
      0.027(10.0 ug E2), 1.988+/-0.049(10.0 ug E2 +100.0 ug tamoxifen) (F = 628.103, P
      < 0.01). The difference between any two groups were also significant (all P value
      were less than 0.05). The close relation between the percentage of
      avascular/total retinal area and MDA concentration was also verified (r = 0.981,
      P < 0.01). CONCLUSION: Oxidative stress responses play a pivotal role in OIR, by
      means of receptor pathway. E2 can alleviate oxidative stress reaction, and thus
      ameliorate the severity of oxygen induced retinopathy.

PMID- 23554625
TI  - Inhibition of TGF-beta1 by eNOS gene transfer provides cardiac protection after
      myocardial infarction.
AB  - OBJECTIVE: Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) have
      been implicated in protection against myocardial ischemia injury. This study was
      designed to explore a new method of therapy for myocardial injury by eNOS gene
      transfection. METHODS: A rat model of myocardial infarction (MI) was established
      by left anterior descending (LAD) coronary artery ligation. eNOS gene in an
      adenovirus vector was delivered locally into the rat heart and hemodynamic
      parameters were examined after 3 weeks, Matrix metalloproteinase-2 and 9 (MMP-2,
      MMP-9) mRNA were measured by reverse transcription polymerase chain reaction (RT
      PCR), and the protein levels of eNOS, caspase-3, and transforming grouth factor
      beta1 (TGF-beta1) were determined by western blot assay. RESULTS: eNOS gene
      transfer significantly reduced cardiomyocyte apoptosis and improved cardiac
      function. In addition, eNOS significantly reduced the mRNA levels of MMP-2 and
      MMP-9. In the eNOS gene transfected group, the activation of caspase-3 and TGF
      beta1 were decreased. However, the protection was reversed by administration of
      the NOS inhibitor, N(omega)-nitro-l-arginine methyl ester (L-NAME). CONCLUSION:
      These results demonstrate that the eNOS provides cardiac protection after
      myocardial infarction injury through inhibition of cardiac apoptosis and collagen
      deposition, and suppression of TGF-beta1.

PMID- 23554626
TI  - Protective effect of magnesium isoglycyrrhizinate on ethanol-induced testicular
      injuries in mice.
AB  - OBJECTIVE: Ethanol treatment induces an increase in oxidative stress. As licorice
      compounds are potent antioxidants, our aim was to examine whether magnesium
      isoglycyrrhizinate attenuated lipid peroxidation, the major end-point of
      oxidative damage resulting from ethanol administration. METHODS: Four groups(18
      animals in each group) of male Kunming mice were used. The first group served as
      control and received 0.4 ml normal saline daily for 18 days orally. The second
      group of mice was given 56% ethanol at 16 ml/kg body weight per day for 18 days
      orally. The third group was given the same dose of ethanol and administrated
      magnesium isoglycyrrhizinate (15 mg/kg.d, i.p.) for 18 days. The fourth group was
      given the same dose of ethanol and administrated with magnesium
      isoglycyrrhizinate (45 mg/kg.d, i.p.) for 18 days. Twenty four hours after 9 days
      or 18 days of treatment the mice were sacrificed using 10% chloral hydrate. Sperm
      counts and motility in the epididymis were assessed. The lipid peroxidation and
      antioxidants of testicular mitochondria were also determined. The pathological
      changes of testicle tissue of the mice were observed by light microscopy.
      RESULTS: Magnesium isoglycyrrhizinate effectively prevented the ethanol-induced
      seminiferous epithelium disorganization and degeneration of Sertoli cells and
      germ cells. Sperm counts and motility of the magnesium isoglycyrrhizinate treated
      groups were higher than those of the alcohol treated group, but were lower than
      those of the control group. The drug exhibited an ability to counteract ethanol
      induced oxidative challenge as it effectively reduced testicular malondialdehyde
      (MDA) and increased the activities of superoxide dismutase and glutathione
      peroxidase. CONCLUSION: Magnesium isoglycyrrhizinate is able to inhibit the
      ethanol-induced lipid peroxidation and has a protective effect against testicular
      oxidative injury.

PMID- 23554627
TI  - In vivo and in vitro effects of QHF combined with chemotherapy on hepatocellular
      carcinoma.
AB  - OBJECTIVE: To investigate the synergistic anti-tumor effect of QHF (a Chinese
      medicine formula with anti-tumor active ingredients, including 800 mg/kg
      Cinobufotalin, 14 mg/kg Ginsenoside Rg3, 5.5 mg/kg Notoginseng and 100 mg/kg
      Lentinan) when combined with the chemotherapy drug cisplatin (DDP). METHODS:
      Hepatocellular carcinoma H22 cells were implanted into mice and after the
      transplants were successfully established the animals were divided into four
      groups, namely a normal saline(NS) control group, QHF group, DDP group and
      QHF+DDP group. The tumor growth was monitored and the survival time determined.
      In vitro studies employing H22 cells used the first three groups, and determined
      the effects of QHF and DDP on tumor cell cycle distribution, apoptosis and
      morphologic changes in vitro. RESULTS: QHF significantly inhibited the growth of
      tumors and prolonged the survival time of mice with hepatocellular carcinomas.
      QHF combined with DDP could attenuate DDP-induced leucopenia, spleen and thymus
      atrophy and other indicators of toxicity. The inhibition rate of tumor growth
      reached 82.54% with QHF+DDP, and QHF prolonged the life span of DDP-treated mice
      by 66.83%. In the in vitro experiments tumor cells showed morphological changes
      characteristic of apoptosis by both light and transmission electron microscopy in
      the QHF group, and the apoptosis rate was 33.85%. Moreover, the proportion of
      cells in the G0/G1 phase was increased and those in the S-phase decreased.
      CONCLUSION: QHF combined with DDP could significantly inhibit tumor growth,
      induce the apoptosis of tumor cells and effectively attenuate DDP toxicity.

PMID- 23554628
TI  - Vascular smooth muscle cell differentiation-2010.
AB  - Vascular smooth muscle cells have attracted considerable interest as a model for
      a flexible program of gene expression. This cell type arises throughout the
      embryo body plan via poorly understood signaling cascades that direct the
      expression of transcription factors and microRNAs which, in turn, orchestrate the
      activation of contractile genes collectively defining this cell lineage. The
      discovery of myocardin and its close association with serum response factor has
      represented a major break-through for the molecular understanding of vascular
      smooth muscle cell differentiation. Retinoids have been shown to improve the
      outcome of vessel wall remodeling following injury and have provided further
      insights into the molecular circuitry that defines the vascular smooth muscle
      cell phenotype. This review summarizes the progress to date in each of these
      areas of vascular smooth muscle cell biology.

PMID- 23554629
TI  - Understanding alternative splicing of Cav1.2 calcium channels for a new approach
      towards individualized medicine.
AB  - Calcium channel blockers (CCBs) are widely used to treat cardiovascular diseases
      such as hypertension, angina pectoris, hypertrophic cardiomyopathy, and
      supraventricular tachycardia. CCBs selectively inhibit the inward flow of calcium
      ions through voltage-gated calcium channels, particularly Cav1.2, that are
      expressed in the cardiovascular system. Changes to the molecular structure of
      Cav1.2 channels could affect sensitivity of the channels to blockade by CCBs.
      Recently, extensive alternative splicing was found in Cav1.2 channels that
      generated wide phenotypic variations. Cardiac and smooth muscles express slightly
      different, but functionally important Cav1.2 splice variants. Alternative
      splicing could also modulate the gating properties of the channels and giving
      rise to different responses to inhibition by CCBs. Importantly, alternative
      splicing of Cav1.2 channels may play an important role to influence the outcome
      of many cardiovascular disorders. Therefore, the understanding of how alternative
      splicing impacts Cav1.2 channels pharmacology in various diseases and different
      organs may provide the possibility for individualized therapy with minimal side
      effects.

PMID- 23554631
TI  - HGF percutaneous endocardial injection induces cardiomyocyte proliferation and
      rescues cardiac function in pigs.
AB  - OBJECTIVE: To investigate the effect of cardiomyocyte proliferation induced by
      human hepatocyte growth factor (HGF) in pigs with chronic myocardial infarction
      (CMI). METHODS: A steerable, deflectable 7F catheter incorporating a 27-guage
      needle was advanced percutaneously to the left ventricular myocardium of 18 pigs
      with CMI. Pigs were randomized (1:1:1) to receive adenoviral vector HGF (total
      dose, 1*10(10) genome copies), which was administered as five injections into the
      infarcted myocardium (total, 1.0 mL), or saline, or Ad-null (control groups).
      Injections were guided by Ensite NavX left ventricular electroanatomical mapping.
      HGF and cyclin proteins were detected by western blot and immunoprecipitation
      analysis. Histological and immunohistochemical analysis determined proliferating
      cardiomyocytes. Myocardial perfusion and cardiac function were estimated by Gated
      Single Photon Emission Computed Tomography (G-SPECT). RESULTS: Western blot
      analyses showed that HGF were predominantly expressed in the infarct core and
      border in the myocardium of the infarcted heart. G-SPECT analysis indicated that
      the HGF group had better cardiac function and myocardial perfusion four weeks
      after the injection of Ad-HGF than before the injection of Ad-HGF. After
      treatment there were more proliferating cardiomyocytes in the HGF group compared
      to either of the control groups. Furthermore, the HGF group myocardial samples
      expressed higher levels of p-Akt, cyclin A, cyclin E, cyclin D1, cdk2, cdk4 than
      those in the control groups. CONCLUSION: The over-expression of HGF activates pro
      survival pathways, induces cardiomyocyte proliferation, and improves the
      perfusion and function of the porcine CMI heart.

PMID- 23554630
TI  - Elevated expression of mature miR-21 and miR-155 in cancerous gastric tissues
      from Chinese patients with gastric cancer.
AB  - OBJECTIVE: MicroRNA (miRNA) expression is deregulated in many types of human
      cancers. We sought to investigate the expression patterns of the miRNAs, miR-21,
      miR-145 and miR-155 in sporadic gastric cancer in a Chinese population. METHODS:
      Total RNA was extracted from archived gastric cancer tissues and adjacent non
      cancerous tissues from 20 pairs of paraffin-embedded specimens. Expression levels
      of miR-21, miR-145 and miR-155 were detected by quantitative reverse
      transcriptase PCR using a specific stem-loop primer, with U6 as the internal
      reference gene. RESULTS: The expression of miR-21 and miR-155 in gastric cancer
      samples was significantly higher than in paired non-cancerous samples (P < 0.05).
      There was no statistically significant difference in expression levels of miR-145
      between cancerous and non-cancerous tissues (P > 0.05). CONCLUSION: In Chinese
      sporadic gastric cancer tissues, the expressions of the oncogenic miR-21 and miR
      155 were significantly up-regulated, while the expression of the tumor suppressor
      miR-145 was decreased, although this decrease was not statistically significant.
      Thus there is specificity in the miRNA expression pattern in gastric cancers in
      the Chinese population.

PMID- 23554633
TI  - RNAi knockdown of C-erbB2 expression inhibits salivary gland adenoid cystic
      carcinoma SACC-83 cell growth in vitro.
AB  - OBJECTIVE: To knockdown the C-erbB2 gene in salivary gland adenoid cystic
      carcinoma SACC-83 cells using RNA interference, and determine the effect of
      silencing C-erbB2 on cell proliferation. METHODS: C-erbB2-siRNA was transfected
      into SACC-83 cells. RT-PCR and immunohistochemistry were used to detect C-erbB2
      expression in SACC-83 cells. Cell proliferation was measured by the MTT assay and
      gene knockdown was achieved by RNA interference. Apoptosis was analyzed by flow
      cytometry. RESULTS: Compared with the control, C-erbB2 mRNA expression was
      decreased in the C-erbB2-siRNA transfection group, and immunohistochemical
      analysis indicated that C-erbB2 protein expression was decreased. After C-erbB2
      siRNA was transfected for 48 h, absorbance at 570 nm (MTT) was 0.185+/-0.021
      compared with 0.354+/-0.034, 0.299+/-0.053, and 0.314+/-0.049 in the blank
      control, liposome control and negative control siRNA groups, respectively. The
      differences were statistically significant (P < 0.05) between the C-erbB2-siRNA
      group and the control groups. Following the C-erbB2 knockdown, the percentage of
      apoptotic cells was 5.63% compared with 2.04%, 2.85%, and 2.98% in the three
      control groups, respectively. Proliferation of SACC-83 cells was inhibited, and
      early apoptotic cells were increased. CONCLUSION: RNA interference can
      effectively silence C-erbB2 gene expression and inhibit growth of SACC-83 cells,
      which indicates the potential of targeting this gene as a novel gene therapy
      approach for the treatment of salivary gland adenoid cystic carcinoma.

PMID- 23554632
TI  - Weighted Markov chains for forecasting and analysis in Incidence of infectious
      diseases in jiangsu Province, China.
AB  - This paper first applies the sequential cluster method to set up the
      classification standard of infectious disease incidence state based on the fact
      that there are many uncertainty characteristics in the incidence course. Then the
      paper presents a weighted Markov chain, a method which is used to predict the
      future incidence state. This method assumes the standardized self-coefficients as
      weights based on the special characteristics of infectious disease incidence
      being a dependent stochastic variable. It also analyzes the characteristics of
      infectious diseases incidence via the Markov chain Monte Carlo method to make the
      long-term benefit of decision optimal. Our method is successfully validated using
      existing incidents data of infectious diseases in Jiangsu Province. In summation,
      this paper proposes ways to improve the accuracy of the weighted Markov chain,
      specifically in the field of infection epidemiology.

PMID- 23554634
TI  - Identification of the metabolites of polybrominated diphenyl ether 99 and its
      related cytochrome P450s.
AB  - OBJECTIVE: To investigate the metabolites of polybrominated diphenyl ether 99
      (BDE-99) and its related cytochrome P450s in an in vitro system. METHODS: Rat
      primary hepatocytes were isolated and treated with BDE-99 for 24-72 h.
      Metabolites were then extracted from the hepatocytes and media, and detected by
      GC/MS. Several mRNAs of metabolic enzymes were also extracted from the same cells
      and the gene expression levels were determined using quantitative real-time PCR.
      In addition, selected recombinant cytochrome P450s (CYPs) were expressed in a
      bacurovirus/sf9 system, and these were further used to explore the metabolism of
      BDE-99 in vitro. The parent depletion approach was used for screening the ability
      of CYPs to eliminate BDE-99. RESULTS: A reductively debrominated metabolite, BDE
      47, and three oxidative metabolites, 2, 4, 5-tribromophenol, 5-OH-BDE-47, and 5'
      OH-BDE-99, were identified from the BDE-99-treated rat hepatocytes, whereas no
      MeO metabolite was detected in the system. RT-PCR analysis showed that CYP
      3A23/3A1, 1A2, and 2B1/2 were induced by BDE-99. Furthermore, using the
      heterological expressed CYP proteins in in vitro BDE-99 metabolism experiments we
      found that CYP1A2 and CYP3A4 showed the highest metabolic efficiency for BDE-99,
      with the metabolic clearance rates of CYP1A2 and CYP3A4 being 30.3% and 27.7%,
      respectively. CYP1A1 and CYP2A6 displayed relatively low clearance rates, while
      CYP2E1 seemed not to be associated with the BDE-99 metabolism. CONCLUSIONS: In
      our in vitro rat primary hepatocyte metabolism system, four metabolites of BDE-99
      were identified, and CYP3A4 and CYP1A2 were demonstrated to be involved in the
      BDE-99 metabolism.

PMID- 23554635
TI  - CYP17 T27C polymorphism and prostate cancer risk: a meta-analysis based on 31
      studies.
AB  - OBJECTIVE: The cytochrome P450 17alpha-hydroxylase (CYP17) plays a vital role in
      androgen biosynthesis. A T-to-C polymorphism in the 5' promoter region of CYP17
      has been implicated as a risk factor for prostate cancer, but the results of
      individual studies are inconclusive or controversial. To derive a more precise
      estimation of the relationship, we performed an updated meta-analysis from 31
      studies based on 27 publications. METHODS: A comprehensive search was conducted
      to examine all the eligible studies of CYP17 polymorphism and prostate cancer
      risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the
      strength of the association. RESULTS: Overall, individuals with CC/CT genotype
      were not associated with prostate cancer risk (CC vs. TT: OR = 1.03, 95% CI =
      0.86-1.24, P = 0.72, P heterogeneity < 0.0001; CT vs. TT: OR = 0.99, 95% CI =
      0.87-1.12, P = 0.88, P heterogeneity = 0.0006). In the stratified analysis by
      ethnicity, there was a significantly increased risk of prostate cancer among
      individuals of African descent under the recessive model (OR = 1.56, 95% CI =
      1.01-2.39, P = 0.04, P heterogeneity = 0.65). CONCLUSION: This meta-analysis
      suggested that CYP17 polymorphism might be associated with prostate cancer risk
      among individuals of African descent.

PMID- 23554636
TI  - Effects of heme precursors on CYP1A2 and POR expression in the
      baculovirus/Spodoptera frugiperda system.
AB  - OBJECTIVE: CYP1A2 and NADPH-CYP450 oxidoreductase (POR) were expressed in the
      baculovirus/Spodoptera frugiperda (sf9) system. The aim of this study was to
      investigate the effects of heme precursors on the expression of CYP1A2 and POR.
      METHODS: The heme precursors [delta-Aminolaevulinic Acid (5-ALA), Fe(3+) and
      hemin] were introduced into the system to evaluate their effects on the
      expression of CYP1A2, POR and their co-expression. All the proteins were
      identified using immunoblotting, CO-difference spectroscopy, or cytochrome c
      assay. RESULTS: In the present study, functional CYP1A2 and POR were successfully
      expressed in the baculovirus/sf9 system, and both of them showed high activities.
      Co-addition of 5-ALA and Fe(3+) significantly improved expression of CYP1A2 by
      about 50% compared with the addition of 5-ALA, Fe(3+) or hemin alone. Either co
      addition of 5-ALA and Fe(3+) or addition of 5-ALA or Fe(3+) alone improved the
      POR expression level 2 fold and its activity 7-10 fold compared with control (no
      addition). However, unlike CYP1A2, there was no difference between the co
      addition and addition of these heme precursors alone. Different ratios of
      BvCYP1A2 to BvPOR also affected the co-expression of CYP1A2 and POR, with a 3:1
      ratio of BvCYP1A2 / BvPOR significantly increasing their co-expression.
      Surprisingly, the addition of 0.1 mM 5-ALA or Fe(3+) alone, but not their co
      addition, could significantly improve the CYP1A2 and POR co-expression (P <
      0.05). CONCLUSION: 5-ALA and Fe(3+) increased the expression of CYP1A2 and POR in
      a baculovirus/sf9 system, but the pattern of their expression was different
      between their expression alone and co-expression.

PMID- 23554637
TI  - Changes of free radicals and digestive enzymes in saliva in cases with deficiency
      in spleen-yin syndrome.
AB  - OBJECTIVE: To explore the nature of deficiency in spleen-yin syndrome, which
      could provide scientific theoretical support and practical guidance for clinical
      Traditional Chinese Medicine (TCM) syndrome differentiation based on biology, and
      had a strong clinical significance. METHODS: Serum Cu and Zn were detected by
      atomic absorption spectrophotometer, serum vitamin E by high performance liquid
      chromatography, serum vitamin C by 2,4-Dinitrophenylhydrazine Colorimetry, total
      superoxide dismutase (SOD) and Cu and Zn-SOD by the xanthine oxidase method, and
      malondialdehyde (MDA) by the 2-thiobarbituric acid method (TBA). Total
      antioxidant capacity was detected by a colorimetry kit. Amylase Activity was
      detected by an automatic biochemical analyzer. Lysozyme was detected by lysozyme
      detection plate, the diameter of bacteriolysis circle was measured and the
      corresponding content of lysozyme was obtained from a table of standard curve
      values. RESULTS: No significant difference in total SOD and Cu, Zn-SOD was found
      between deficiency in spleen-yin group and normal group. However, such factors in
      deficiency in kidney-yin group were significantly lower than the other groups (P
      < 0.05). The MDA content in both deficiency in spleen-yin group and deficiency in
      kidney-yin group were significantly higher than that of normal group (P < 0.05),
      while the total antioxidant capacity was significantly lower than normal group (P
      < 0.05). The vitamin E content in deficiency in kidney-yin group was
      significantly lower than that in the other two groups (P < 0.05). No significant
      difference in the contents of vitamin C, Cu and Zn were observed in these groups.
      The Zn/Cu level in deficiency in kidney-yin group and the vitamin E level in
      deficiency in spleen-yin group decreased, but with no significant difference.
      Amylase activity in unit time in cases with deficiency in spleen-yin was lower
      than and had significant differences with that in normal cases, and higher than
      that in cases with deficiency in kidney-yin. The sectional velocity of saliva and
      the ratio of lysozyme in normal case group were significantly higher than other
      two groups, while deficiency in the spleen-yin group was significantly higher
      than the deficiency in kidney-yin group. CONCLUSION: All the results indicated
      that the objective pathological mechanism between the deficiency in spleen-yin
      and deficiency in kidney-yin was different.

PMID- 23554638
TI  - Morphological and molecular basis of ovarian serous carcinoma.
AB  - Serous carcinoma is the most common type of epithelial ovarian cancer. In this
      review, we provide a comprehensive picture of ovarian serous cancers from
      multiple aspects: the first part of this review summarizes the morphological,
      histological, and immunological signatures of ovarian serous carcinoma;
      subsequently, we review the history of the evolvement of different grading
      systems used in ovarian serous cancer; in the end, we focus on characterizing the
      genetics that underlie the 2-tiered pathways through which ovarian serous cancers
      are believed to arise: the low-grade and the high-grade pathways.

PMID- 23554639
TI  - Inactivation of Staphylococcus aureus and Enterococcus faecalis by a direct
      current, cold atmospheric-pressure air plasma microjet.
AB  - OBJECTIVE: A direct-current, cold atmospheric-pressure air plasma microjet (PMJ)
      was performed to inactivate Staphylococcus aureus (S. aureus) and Enterococcus
      faecalis (E. faecalis) in air. The process of sterilization and morphology of
      bacteria was observed. We wish to know the possible inactivation mechanisms of
      PMJ and explore a potential application in dental and other temperature sensitive
      treatment. METHODS: In this study, we employed a direct current, atmospheric
      pressure, cold air PMJ to inactivate bacterias. Scanning electron microscopy was
      employed to evaluate the morphology of S. aureus and showed rupture of cell walls
      after the plasma treatment and Optical emission spectrum (OES) were used to
      understand the possible inactivation mechanisms of PMJ. RESULTS: The inactivation
      rates could reach 100% in 5 min. When the distance between the exit nozzle of the
      PMJ device and Petri dish was extended from 1 cm to 3 cm, effective inactivation
      was also observed with a similar inactivation curve. CONCLUSION: The inactivation
      of bacteria is attributed to the abundant reactive oxygen and nitrogen species,
      as well as ultroviolet radiation in the plasma. Different life spans and
      defensibilities of these killing agents may hold the key to understanding the
      different inactivation curves at different treatment distances.

PMID- 23554640
TI  - Association of transforming growth factor-beta1 gene variants with risk of coal
      workers' pneumoconiosis.
AB  - OBJECTIVE: The aim of this case-control study was to explore whether five tagging
      single nucleotide polymorphisms (tSNPs) within the transforming growth factor
      beta1 (TGF-beta1) gene were involved in manifestation of inflammatory and
      fibrotic processes associated with coal workers' pneumoconiosis (CWP). METHODS:
      The study included 508 CWP patients and 526 controls who were underground coal
      miners from Xuzhou Mining Business Group. Five tSNPs were selected from the
      HapMap and detected by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. RESULTS: The single SNP analysis showed that the
      genotype frequencies of SNP2 (rs1800470, +869T/C, extron 1) and SNP5 (rs11466345,
      intron 5) in CWP cases were significantly different from those in controls.
      Multivariate logistic regression analysis revealed that SNP2 (rs1800470) CC
      genotype was associated with decreased risk of CWP (OR = 0.50, 95% CI = 0.32
      0.78), which was evident among subgroups of those never smoke (OR = 0.40, 95%CI =
      0.24-0.66), cases with stage II (OR = 0.41, 95%CI = 0.22-0.76) and exposure
      period (< 28 y: OR = 0.54, 95%CI = 0.31-0.95; >=28 y: OR = 0.52, 95%CI = 0.32
      0.96). However, the SNP5 (rs11466345) GG genotype was associated with an
      increased risk of CWP (OR = 2.5, 95%CI = 1.36-4.57), and further stratification
      analysis showed that the risk of CWP was increased in both smoking and nonsmoking
      groups, shorter and longer exposure groups, while the risk of CWP was only
      increased in patients with stage I and II. CONCLUSION: This study suggests that
      TGF-beta1 polymorphisms may contribute to susceptibility of CWP.

PMID- 23554641
TI  - Ultraviolet- attenuated cercariae of Schistosoma japonicum fail to effectively
      induce a Th1 response in spite of up-regulating expression of cytotoxicity
      related genes in C57BL/6 mice.
AB  - OBJECTIVE: To better understand the reason that Schistosoma japonicum (S.
      japonicum) ultraviolet (UV)-radiated cercariae could not induce high level of
      protection in C57BL/6 mice. METHODS: Microarray technology was performed to
      investigate the gene transcription profile in skin draining lymph nodes (sdLNs)
      at 1 w after exposure to attenuated cercariae (AC) or normal cercariae (NC) of S.
      japonicum in C57BL/6 mice. The expressions of some representative genes were
      further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2
      cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in
      spleens from AC-vaccinated and NC-infected mice were analyzed by real-time PCR at
      w 3 and 6 post-exposure. RESULTS: The gene expressions of Th1 cytokines,
      including interferon-gamma (IFN-gamma), interleukin (IL)-12 and tumor necrosis
      factor-alpha (TNF-alpha) in the sdLNs were significantly lower in AC-vaccinated
      mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2-
      cytokines, including IFN-gamma, IL-12, TNF-alpha, IL-4 and IL-10, in the spleens
      from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In
      addition, cytotoxicity-related molecules including granzyme A, granzyme B,
      granzyme K, perforin 1 and Fas L were up-regulated from the early stage of
      vaccination, and peaked at the 3(rd) w after vaccination with UV-AC. CONCLUSION:
      UV-AC of S. japonicum could not effectively induce a Th1 response in C57BL/6
      mice, which may be an explanation for the low protection against parasite
      challenge, and the role played by up-regulated expression of cytotoxicity-related
      genes in mice needs to be further investigated.

PMID- 23554642
TI  - Antigen presenting cells may be able to distinguish between normal and radiated
      Schistosoma japonicum cercaria: an in vitro observation.
AB  - OBJECTIVE: To observe the discrepancies of responses induced by Schistosoma
      japonicum (S. japonicum) normal cercaria antigen (NCA) and ultraviolet (UV) 
      radiation-attenuated cercaria antigen (UVACA) in an in vitro system. METHODS: S.
      japonicum cercariae were collected and UVACA and NCA were prepared. Mouse
      macrophage model cells (RAW 264.7) were treated with medium, NCA (40 ug/mL) or
      UVACA (40 ug/mL) in the presence or absence of recombinant mouse interferon gamma
      (rmIFN-gamma; 4 ng/mL) for 48 h. Cell surface staining and flow cytometry were
      used to assess the major histocompatibility complex (MHC)gamma; 4 ng/mL) for 48
      h. Cell surface staining and flow cytometry were used to assess the major
      histocompatibility complex (MHC) II expression, and data were expressed as mean
      fluorescence intensities (MFI). Interleukin (IL) -10, IL-6 and prostaglandin E2
      (PGE2) in cell culture supernatant were evaluated by commercial enzyme-linked
      immunosorbent assays. RESULTS: NCA significantly suppressed IFN-gamma-induced MHC
      II expression on RAW 264.7 cells. In the presence of IFN-gamma, NCA significantly
      promoted IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells. In the presence of
      IFN-gamma, UVACA significantly promoted IL-10 but not IL-6 and PGE2 secretion
      from RAW 264.7 cells and showed no effect on IFN-gamma-induced MHC II expression.
      Compared with UVACA, NCA significantly suppressed IFN-gamma-induced MHC II
      expression and significantly promoted IL-6, PGE2 and IL-10 secretion from RAW
      264.7 cells. CONCLUSION: RAW 264.7 cells respond differently to NCA and UVACA.
      NCA can significantly suppress IFN-gamma-induced MHC II expression and
      significantly promote IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells
      compared with UVACA.

PMID- 23554643
TI  - Arrhythmogenic properties of dismantling cadherin-mediated adhesion in murine
      hearts.
AB  - OBJECTIVE: To evaluate the arrhythmogenic effects of dismantling cadherin
      mediated adhesion by recombinant mouse aminopeptidase N (rmAPN) in murine hearts.
      METHODS: rmAPN was incubated with cultured neonatal rat cardiomyocytes as well as
      being infused in adult mice. The cell-cell connections were immunolabelled and
      observed by laser confocal microscopy. Disruption of the N-terminal of N-cadherin
      (N-cad) was detected by western blot and quantitative immunofluorescence. The
      risk of inducible ventricular tachyarrhythmia was evaluated in mice by an
      electrophysiological study. RESULTS: Disrupted cell-cell contact was observed in
      cultured neonatal rat cardiomyocytes in response to 30-40 ng/uL rmAPN. Loss of
      the N-terminal in N-cad and altered distribution of connexin 43 (Cx43) were
      observed in hearts from rmAPN-infused mice. In addition, a reduction of
      phosphorylated Cx43 was also detected concomitant with redistribution of Cx43.
      Electrophysiological studies of rmAPN-infused mice showed prolonged QRS duration
      and increased inducibility of ventricular tachycardias. CONCLUSION: Disruption of
      N-cad by rmAPN contributes to gap junction remodeling and may elicit
      arrhythmogenic effects. The disorder of adherent junctions by proteolytic enzymes
      may play an important role in arrhythmogenic mechanisms in correlated diseases.

PMID- 23554645
TI  - Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-kappaB and
      c-Jun N-terminal kinase in human mesangial cells.
AB  - OBJECTIVE: Monocytes/macrophages, proinflammatory cytokines and chemokines are
      important in the pathogenesis of glomerulonephritis. Interleukin (IL) -13 has
      been shown to exert potent anti-inflammatory properties. This study was designed
      to investigate the effect of IL-13 on the expression of proinflammatory
      cytokines, chemokines and profibrogenic cytokines and the involved molecular
      mechanism in cultured human mesangial cells (HMCs). METHODS: The expressions of
      proinflammatory cytokines, chemokines and profibrogenic cytokines were determined
      by ribonuclease protection assay (RPA). Activity of nuclear factor-kappa B (NF
      kappaB) and activator protein-1 (AP-1) was examined by electrophoretic mobility
      shift assay (EMSA). NF-kappaB subunit p65 nuclear transportation and c-Jun N
      terminal kinase (JNK) activity were assayed by immunoblot. RESULTS: Recombinant
      IL-13 inhibited tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-1beta,
      monocyte chemoattractant protein-1 (MCP-1), IL-8, and transforming growth factor
      beta1 (TGF-beta1) mRNA expressions in a dose-dependent manner.
      Lipopolysacchorides (LPS) dramatically increased NF-kappaB DNA binding activity
      of HMCs, which was inhibited by IL-13 in a dose-dependent manner. LPS-activated
      NF-kappaB contained p50 and p65 dimers, but not c-Rel subunit. IL-13 blocked LPS
      induced NF-kappaB subunit p65. LPS stimulated JNK/AP-1 activation, which was
      inhibited by IL-13 in a dose-dependent manner. CONCLUSION: IL-13 inhibits
      proinflammatory cytokines, chemokines, and profibrogenic cytokines synthesis by
      blocking NF-kappaB and JNK/AP-1 activation. These observations point to the
      importance of IL-13 in the modulation of inflammatory processes in the renal
      glomerulus.

PMID- 23554644
TI  - Activation of calcium-sensing receptors is associated with apoptosis in a model
      of simulated cardiomyocytes ischemia/reperfusion.
AB  - OBJECTIVE: Calcium-sensing receptors (CaSRs) are G-protein coupled receptors
      which maintain systemic calcium homeostasis and participate in hormone secretion,
      activation of ion channels, cell apoptosis, proliferation, and differentiation.
      Previous studies have shown that CaSRs induce apoptosis in isolated adult rat
      heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP3 signaling
      transduction. However, little knowledge is presently available concerning the
      role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal
      cardiomyocytes. METHODS: Primary neonatal rat ventricular cardiomyocytes were
      incubated in ischemiamimetic solution for 2 h, and then re-incubated in normal
      culture medium for 24 h to establish a model of simulated ischemia/reperfusion
      (I/R). Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL). The expression of CaSRs mRNA
      was detected by real-time reverse transcription polymerase chain reaction (RT
      PCR). In addition, the expressions of caspase-3 and Bcl-2 were analyzed by
      western blot. RESULTS: The simulated I/R enhanced the expression of CaSRs and
      cardiomyocyte apoptosis. GdCl3, a specific activator of CaSRs, further increased
      the expression of CaSRs and cardiomyocyte apoptosis, along with up-regulation of
      caspase-3 and down-regulation of Bcl-2. CONCLUSION: CaSRs are associated with I/R
      injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing
      Bcl-2 and promoting caspase-3 expression.

PMID- 23554646
TI  - The effects of diltiazem in renal transplantation patients treated with
      cyclosporine A.
AB  - OBJECTIVE: To investigate the effects of diltiazem and cyclosporine A (CsA)
      combination therapy on protecting the kidney, promoting graft functioning and
      improving post-transplanted kidney recovery. METHODS: The blood concentrations of
      CsA, the condition of the post-transplant kidney, the rate of acute rejection
      (AR), as well as hepatic and renal toxicity in 636 cases of renal transplant
      recipients were determined after being treated by CsA, with or without diltiazem.
      RESULTS: Compared with the control group which received CsA, mycophenolate
      mofetil (MMF) and prednisolone (Pred) but lacked diltiazem, the group receiving
      these agents together with diltiazem required reduced dosage of CsA (P < 0.01),
      while blood concentrations of CsA were significantly increased (P < 0.01); the
      recovery time of graft function was reduced from (6.2+/-1.5) d to (3.9+/-1.4) d
      (P < 0.01), and the rate of AR was decreased from 13.2% to 7.9% (P < 0.01).
      CONCLUSION: In renal transplantation patients treated with CsA and diltiazem,
      blood concentrations of CsA were increased while the dosage was decreased. This
      efficient combination therapy reduced patients' economic burden, at the same time
      retained kidney function, promoted graft function recovery and decreased hepatic
      and renal toxicity and the rate of AR.

PMID- 23554647
TI  - The cardioprotection induced by lipopolysaccharide involves phosphoinositide 3
      kinase/Akt and high mobility group box 1 pathways.
AB  - OBJECTIVE: The mechanisms by which lipopolysaccharide (LPS) pretreatment induces
      cardioprotection following ischaemia/reperfusion (I/R) have not been fully
      elucidated. We hypothesized that activation of phosphoinositide 3-kinase
      (PI3K)/Akt and high mobility group box 1 (HMGBx1) signaling plays an important
      role in LPS-induced cardioprotection. METHODS: In in vivo experiments, age- and
      weight- matched male C57BL/10Sc wild type mice were pretreated with LPS before
      ligation of the left anterior descending coronary followed by reperfusion.
      Infarction size was examined by triphenyltetrazolium chloride (TTC) staining.
      Akt, phospho-Akt, and HMGBx1 were assessed by immunoblotting with appropriate
      primary antibodies. In situ cardiac myocyte apoptosis was examined by the TdT
      mediated dUTP nick-end labeling (TUNEL) assay. In an in vitro study, rat cardiac
      myoblasts (H9c2) were subdivided into two groups, and only one was pretreated
      with LPS. After pretreatment, the cells were transferred into a hypoxic chamber
      under 0.5% O2. Levels of HMGBx1 were assessed by immunoblot. RESULTS: In the in
      vivo experiment, pretreatment with LPS reduced the at risk infarct size by 70.6%
      and the left ventricle infarct size by 64.93% respectively. Pretreatment with LPS
      also reduced cardiac myocytes apoptosis by 39.1% after ischemia and reperfusion.
      The mechanisms of LPS induced cardioprotection involved increasing PI3K/Akt
      activity and decreasing expression of HMGBx1. In the in vitro study, pretreatment
      with LPS reduced the level of HMGBx1 in H9c2 cell cytoplasm following hypoxia.
      CONCLUSION: The results suggest that the cardioprotection following I/R induced
      by LPS pretreatment involves PI3K/Akt and HMGBx1 pathways.

PMID- 23554648
TI  - Epidural abscess after multiple lumbar punctures for labour epidural catheter
      placement.
AB  - Epidural catheterization is routinely used by anaesthesiologists to provide
      labour and post-operative analgesia. In most cases, catheter placement is without
      serious side effects and uneventful. However, epidural abscess is a rare
      complication that may result in severe morbidity. We present a case of epidural
      abscess after labour epidural catheter placement in a healthy 36-year-old female
      who presented on post-partum d 10 with complaints of fever and back pain. She was
      treated with intravenous antibiotics and fully recovered.

PMID- 23554650
TI  - A computational model of the human glucose-insulin regulatory system.
AB  - OBJECTIVE: A computational model of insulin secretion and glucose metabolism for
      assisting the diagnosis of diabetes mellitus in clinical research is introduced.
      The proposed method for the estimation of parameters for a system of ordinary
      differential equations (ODEs) that represent the time course of plasma glucose
      and insulin concentrations during glucose tolerance test (GTT) in physiological
      studies is presented. The aim of this study was to explore how to interpret those
      laboratory glucose and insulin data as well as enhance the Ackerman mathematical
      model. METHODS: Parameters estimation for a system of ODEs was performed by
      minimizing the sum of squared residuals (SSR) function, which quantifies the
      difference between theoretical model predictions and GTT's experimental
      observations. Our proposed perturbation search and multiple-shooting methods were
      applied during the estimating process. RESULTS: Based on the Ackerman's published
      data, we estimated the key parameters by applying R-based iterative computer
      programs. As a result, the theoretically simulated curves perfectly matched the
      experimental data points. Our model showed that the estimated parameters,
      computed frequency and period values, were proven a good indicator of diabetes.
      CONCLUSION: The present paper introduces a computational algorithm to biomedical
      problems, particularly to endocrinology and metabolism fields, which involves two
      coupled differential equations with four parameters describing the glucose
      insulin regulatory system that Ackerman proposed earlier. The enhanced approach
      may provide clinicians in endocrinology and metabolism field insight into the
      transition nature of human metabolic mechanism from normal to impaired glucose
      tolerance.

PMID- 23554649
TI  - Role of human papillomavirus and cell cycle-related variants in squamous cell
      carcinoma of the oropharynx.

PMID- 23554652
TI  - The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes
      of HCV infection among drug users.
AB  - OBJECTIVE: To investigate a possible association of LMP2/LMP7 genes with chronic
      hepatitis C virus (HCV) infection, and to assess whether LMP2/LMP7 genes could
      influence the outcomes of HCV infection among drug users. METHODS: Genomic DNAs
      of 362 anti-HCV sero-positive drug users and 225 control drug users were
      extracted from the peripheral blood leukocytes. The sero-positive patients were
      divided into those who had persistent infection and those who had spontaneously
      cleared the infection. Polymorphisms of LMP genes were determined by PCR combined
      with restriction fragment length polymorphism (RFLP). RESULTS: The distribution
      of LMP2 genotypes among the control, persistent infection and spontaneous
      clearance groups were not different. However, the LMP7 codon 145 Gln/Lys,
      Lys/Lys, and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in
      the persistent infection group than in control group (OR=1.75, 95%CI=1.06~2.90;
      OR=3.16, 95%CI=1.23-8.12; OR = 1.94, 95%CI=1.21-3.12, respectively). Similarly,
      the frequencies of the codon 145 Gln/Lys, Lys/Lys, and Gln/Lys+Lys/Lys genotypes
      were found significantly more frequent in the persistent infection group than in
      the spontaneous clearance group (OR=1.64, 95%CI=1.04-2.57; OR=2.40, 95%CI=1.09
      5.28; OR=1.76, 95%CI=1.15-2.69, respectively). Stratified analysis indicated that
      combined genotype Gln/Lys + Lys/Lys of the LMP7 gene was related to an increasing
      susceptibility to HCV infection (OR=1.91, 95%CI=1.02-3.55; OR=2.19, 95%CI=1.24
      3.89; OR=1.91, 95%CI=1.05-3.48, OR=2.86, 95%CI=1.41-5.78, respectively) and the
      risk of persistent HCV infection (OR=1.94, 95%CI=1.12-3.34; OR=2.02, 95%CI=1.21
      3.38; OR=1.78, 95%CI=1.12-2.85, OR=2.23, 95%CI=1.09-4.58, respectively) among >
      30-year-old, males, the injection drug user (IDU) subjects and/or the shorter
      duration drug users (<=5 y). CONCLUSION: These results suggest that polymorphism
      of the LMP7 gene may have an influence on the outcomes of HCV infection, and is
      one of the factors accounting for the genetic susceptibility to HCV infection
      among drug users.

PMID- 23554651
TI  - Arg462Gln and Asp541Glu polymorphisms in ribonuclease L and prostate cancer risk:
      a meta-analysis.
AB  - OBJECTIVE: The association between ribonuclease L (RNASEL) gene polymorphisms and
      prostate cancer risk has been widely reported, but the results of these studies
      remained controversial and underpowered. We performed a meta-analysis of 28
      studies to evaluate the association between Arg462Gln and Asp541Glu polymorphisms
      in the RNASEL gene and prostate cancer risk. METHODS: Odds ratios (ORs) with 95%
      confidence intervals (CIs) were estimated to assess the association between
      RNASEL polymorphisms and prostate cancer risk. RESULTS: A significantly increased
      prostate cancer risk was found for the Arg462Gln polymorphism in Africans
      (Gln/Gln vs Arg/Arg: OR = 2.50, 95%CI = 1.28-4.87; Gln/Gln vs Gln/Arg + Arg/Arg:
      OR = 2.54, 95%CI = 1.30-4.95), but not in Europeans and Asians. Additionally, the
      Asp541Glu polymorphism was associated with increased total prostate cancer risk
      (Glu-allele vs Asp-allele: OR = 1.04, 95%CI = 1.01-1.07; Glu/Glu vs Asp/Asp: OR =
      1.22, 95%CI = 1.03-1.46; Glu/Glu vs Glu/Asp + Asp/Asp: OR = 1.09, 95%CI = 1.02
      1.16). In the stratified analysis for the Asp541Glu polymorphism, there was a
      significantly increased prostate cancer risk in Africans and Europeans, and in
      hospital-based prostate cancer cases. CONCLUSION: The meta-analysis results
      showed evidence that RNASEL Arg462Gln and Asp541Glu polymorphisms are associated
      with prostate cancer risk and could be low-penetrance prostate cancer
      susceptibility biomarkers.

PMID- 23554653
TI  - Resveratrol prevents interleukin-1beta-induced dysfunction of pancreatic beta
      cells.
AB  - OBJECTIVE: Interleukin-1beta (IL-1beta) plays an important role in the
      development of type 1 and type 2 diabetes mellitus. Resveratrol, a polyphenol, is
      known to have a wide range of pharmacological properties in vitro. In this
      research, we examined the effects of resveratrol on IL-1beta-induced beta-cell
      dysfunction. METHODS: We first evaluated the effect of resveratrol on nitric
      oxide (NO) formation in RINm5F cells stimulated with IL-1beta using the Griess
      method. Next, we performed transient transfection and reporter assays to measure
      the transcriptional activity of peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma). We also used Western blotting analysis to assess the effect of
      resveratrol on inducible nitric oxide synthase (iNOS) expression and nuclear
      factor-kappaB (NF-kappaB) translocation to the nuclei in cells treated with IL
      1beta. In addition, we assessed the transcriptional activity of NF-kappaB using
      an electrophoretic mobility shift assay (EMSA). Finally, we evaluated the effect
      of resveratrol on IL-1beta-induced inhibition of glucose-stimulated insulin
      secretion in freshly isolated rat pancreatic islets. RESULTS: Resveratrol
      significantly suppressed IL-1beta-induced NO production, a finding that
      correlated well with reduced levels of iNOS mRNA and protein. The molecular
      mechanism by which resveratrol inhibited iNOS gene expression appeared to involve
      increased PPAR-gamma activity, which resulted in the inhibition of NF-kappaB
      activation. Further analysis showed that resveratrol could prevent IL-1beta
      induced inhibition of glucose-stimulated insulin secretion in rat islets.
      CONCLUSION: In this study, we demonstrated that resveratrol could protect against
      pancreatic beta-cell dysfunction caused by IL-1beta.

PMID- 23554654
TI  - Effects of propofol on early and late cytokines in lipopolysaccharide-induced
      septic shock in rats.
AB  - OBJECTIVE: It has been reported that the intravenous anesthetic propofol (PPF)
      has anti-inflammatory effects in vitro and in patients. The purpose of this study
      was to investigate whether PPF has anti-inflammatory effects in
      lipopolysaccharide (LPS)-induced septic shock by inhibiting the induction of pro
      inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha)] and high mobility group box 1 (HMGB1) in rats. METHODS: Thirty six male
      Wistar rats were randomly assigned to one of three groups (control group, PPF +
      LPS group and LPS group; n = 12 per group). Control group rats received a 0.9%
      NaCl solution (NS) by the tail vein. The PPF + LPS group rats received PPF (10
      mg/kg bolus, followed by infusion at 10 mg/(kg.h) through a femoral vein
      catheter) 1 h before LPS (7.5 mg/kg) administration via the tail vein. The LPS
      group rats received injection of LPS (7.5 mg/kg) via the tail vein. Hemodynamic
      effects were recorded as well as mortality rates, and plasma cytokine con
      centrations (TNF-alpha, IL-6, HMGB1) were measured for the 24-h observation
      period. RESULTS: The mean arterial pressure and heart rate of the PPF + LPS group
      were more stable than those of the LPS group. The mortality at 24 h after the
      administration of the LPS injection was much higher in the LPS group (58.3%)
      compared to the PPF + LPS group (25.0%). Plasma concentrations of cytokines (IL-6
      and TNF-alpha) and HMGB1 were significantly reduced in the PPF + LPS group
      compared to the LPS group (P < 0.05). CONCLUSION: Pretreatment with PPF reduced
      the mortality rate of rats and attenuated the pro-inflammatory cytokine responses
      in an endotoxin shock model through an anti-inflammatory action inhibiting
      induction of HMGB1.

PMID- 23554655
TI  - Characterization and potential diagnostic application of monoclonal antibodies
      specific to rabies virus.
AB  - OBJECTIVE: Rabies is invariably a fatal encephalomyelitis that is considered to
      be a serious public health problem. It is necessary to develop standard rabies
      virus diagnostic tools, especially for diagnosing the strains prevalent in China.
      METHODS: Monoclonal antibodies (MAbs) specific to rabies virus were produced and
      characterized by enzyme linked immunosorbent assay (ELISA), isotyping, affinity
      assay, immunofluorescence assay (IFA), and immunocytochemistry. The MAb, whose
      affinity was higher for antigen, was used to establish an antigen capture-ELISA
      (AC-ELISA) detection system and test the efficiency by using clinical samples.
      RESULTS: The heavy chain subclasses of two MAbs were all determined to be IgG2a.
      The 3C7 MAb showed stronger reactivity with rabies virus protein than the 2C5 MAb
      in an ELISA analysis, whereas the 3C7 MAb showed the highest affinity for
      antigen. IFA and immunocytochemistry results also indicated that the two MAbs
      could recognize rabies virus protein in its native form in cell samples. Data
      obtained using clinical samples showed that rabies virus could be detected by AC
      ELISA detection system using the 3C7 MAb. CONCLUSION: It was potentially useful
      for the further development of highly sensitive, easily handled, and relatively
      rapid detection kits/tools for rabies surveillance in those areas where rabies is
      endemic, especially in China.

PMID- 23554656
TI  - Evaluation of sperm mitochondrial function using rh123/PI dual fluorescent
      staining in asthenospermia and oligoasthenozoospermia.
AB  - OBJECTIVE: The recent advent of flow cytometry (FCM), coupled with fluorescent
      dyes, has been successfully applied to assess mitochondrial function. The aim of
      this study was to investigate the feasibility and clinical significance of
      detecting sperm mitochondrial function and to evaluate sperm mitochondrial
      function by using Rhodamine 123/propidium (Rh123/PI) dual fluorescent staining
      and FCM in asthenospermia and oligoasthenozoospermia. METHODS: Twenty-five
      fertile men (with normal sperm parameters) and 230 infertile patients were
      examined. Fifty-five patients of the above 230 patients were selected for
      idiopathic infertility samples and were divided into two groups: asthenospermia
      (n = 30) and oligoasthenozoospermia (n = 25). Rh123/PI dual fluorescent staining
      and FCM were carried out to examine sperm mitochondrial function. RESULTS:
      Significant differences were found between the normal and abnormal semen samples
      (P < 0.05) when Rh123(+)/PI(-), Rh123(-)/PI(+) and Rh123(-)/PI(-) sperm were
      examined by FCM, but there was no significant difference between the
      asthenospermia (P = 0.469) and oligoasthenozoospermia group (P = 0.950) when
      Rh123(+)/PI(-) and Rh123(-)/PI(+) sperm were then examined; however, a
      significant difference was found between the 2 groups (P = 0.003) when Rh123(
      )/PI(-) sperm were examined. There was no correlation between Rh123(-)/PI(-)
      sperm and semen parameters in the normal group, but there was a significant
      negative correlation between the sperm concentration and Rh123(-)/PI(-) sperm in
      asthenospermia and oligoasthenozoospermia patients (r = -0.509, -0.660; P =
      0.018, 0.038). CONCLUSION: Rh123/PI dual fluorescent staining and FCM can provide
      reliable information to assess the quality of sperm and reveal differences in
      mitochondrial membrane potential in asthenospermia and oligoasthenozoospermia.

PMID- 23554657
TI  - Clostridium difficile infections in China.
AB  - Clostridium difficile (C. difficile) infection has become one of the major
      hospital-associated infections in Western countries in the last two decades.
      However, there is limited information on the status of C. difficile infection in
      Chinese healthcare settings. Given the large and increasing elderly population
      and the well-recognized problem of over-prescribing of broad spectrum antibiotics
      in China, it is critical to understand the epidemiology and potential risk
      factors that may contribute to C. difficile infection in China. A literature
      review of available published studies, including those in Chinese language-based
      journals, was conducted. A review of the currently available literature suggested
      the presence of C. difficile infections in China, but also suggested that these
      infections were not particularly endemic. This finding should lead to better
      designed and greatly expanded studies to provide a more reliable
      epidemiologically-based conclusion on the actual status of C. difficile infection
      in China, including the identification of any associated risk factors. Such
      information is ultimately valuable to develop appropriate strategies to prevent
      C. difficile infection and the vast negative impact of such infections in China
      and other developing countries.

PMID- 23554658
TI  - Association of the MTHFR C677T polymorphism and bone mineral density in
      postmenopausal women: a meta-analysis.
AB  - Osteoporosis is a condition characterized by low bone mineral density (BMD) and
      micro-architectural changes in the bone tissue. The risk of osteoporosis is
      partly determined by genetic factors. The role of C677T polymorphism of
      methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in
      postmenopausal osteoporosis. However, the relationship between MTHFR polymorphism
      and BMD is still controversial. We carried out a meta-analysis of 5,833 subjects
      to evaluate the association of MTHFR and BMD in postmenopausal women. Databases
      of MEDLINE, Web of Science, Scopus and CNKI were retrieved for all publications
      relating to MTHFR polymorphism and BMD in postmenopausal women. Five eligible
      studies were selected for meta-analysis. All these articles studied the
      association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in
      postmenopausal women. Our analysis suggested that postmenopausal women with the
      TT genotype had lower femoral neck BMD than the women with the CC/CT genotype,
      and the weighted mean difference (WMD) was -0.01 g/cm(2) [95% confidence interval
      (CI): (-0.01, -0.01), P < 0.01]. However, BMD of the lumbar spine of
      postmenopausal women with the TT genotype was not significantly different from
      that of women with the CC/CT genotype. In the random effects model, the WMD
      between the TT and TC/CC genotype was -0.01 g/cm(2) [95% CI: (-0.04, 0.01), P =
      0.32]. The C677T polymorphism of the MTHFR gene is associated with BMD of the
      femoral neck in postmenopausal women. Women with the TT genotype of the MTHFR
      gene have lower BMD, suggesting that the TT genotype may be a risk factor for
      postmenopausal osteoporosis.

PMID- 23554659
TI  - Decoupling of DNA damage response signaling from DNA damages underlies
      temozolomide resistance in glioblastoma cells.
AB  - Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in
      adults. Current therapy includes surgery, radiation and chemotherapy with
      temozolomide (TMZ). Major determinants of clinical response to TMZ include
      methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter
      and mismatch repair (MMR) status. Though the MGMT promoter is methylated in 45%
      of cases, for the first nine months of follow-up, TMZ does not change survival
      outcome. Furthermore, MMR deficiency makes little contribution to clinical
      resistance, suggesting that there exist unrecognized mechanisms of resistance. We
      generated paired GBM cell lines whose resistance was attributed to neither MGMT
      nor MMR. We show that, responding to TMZ, these cells exhibit a decoupling of DNA
      damage response (DDR) from ongoing DNA damages. They display methylation
      resistant synthesis in which ongoing DNA synthesis is not inhibited. They are
      also defective in the activation of the S and G2 phase checkpoint. DDR proteins
      ATM, Chk2, MDC1, NBS1 and gammaH2AX also fail to form discrete foci. These
      results demonstrate that failure of DDR may play an active role in
      chemoresistance to TMZ. DNA damages by TMZ are repaired by MMR proteins in a
      futile, reiterative process, which activates DDR signaling network that
      ultimately leads to the onset of cell death. GBM cells may survive genetic
      insults in the absence of DDR. We anticipate that our findings will lead to more
      studies that seek to further define the role of DDR in ultimately determining the
      fate of a tumor cell in response to TMZ and other DNA methylators.

PMID- 23554660
TI  - MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide
      in U87 glioma stem cells.
AB  - MicroRNAs regulate self renewal and differentiation of cancer stem cells. There,
      we sought to identify the expression of miR-181b in glioma stem cells and
      investigate the biological effect of miR-181b on glioma stem cells in this study.
      MiR-181b expression was measured by real-time PCR in glioma stem cells isolated
      from U87 cells by FACS sorting. After miR-181b was overexpressed in U87 glioma
      stem cells by miR-181b lentiviral expression vector and/or treatment of
      temozolomide, secondary neurosphere assay, soft agar colony assay and MTT assay
      were performed. Compared with U87 cells, the expression of miR-181b was
      significantly decreased in U87 glioma stem cells. Overexpression of miR-181b
      decreased neurosphere formation by U87 glioma stem cells in vitro and suppressed
      colony formation in soft agar, and the cell growth inhibition rates increased in
      a time-dependent manner in U87 glioma stem cells infected with miR-181b
      lentivirus. Furthermore, miR-181b had a synergistic effect on temozolomide
      induced inhibition of secondary neurosphere and soft agar colony, and on cell
      growth inhibition rates. MiR-181b functions as a tumor suppressor that suppresses
      proliferation and reduces chemoresistance to temozolomide in glioma stem cells.

PMID- 23554661
TI  - Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related
      caspase pathway.
AB  - Apoptosis plays an important role in the pathogenesis of viral infections. In
      this study, we investigated the cell death processes during productive HHV-6A
      infection and the underlying mechanisms. Annexin V-PI staining and electron
      microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A
      infection decreased mitochondrial transmembrane potential and led to
      morphological changes of mitochondria. The cell death was associated with
      activation of caspase-3 and cleavage of DNA repair enzyme poly (ADP-ribose)
      polymerase, which is known to be an important substrate for activated caspase-3.
      Caspase-9 was activated significantly in HHV-6A-infected cells, whereas caspase-8
      was not activated obviously. Moreover, HHV-6A infection upregulated Bax and
      downregulated Bcl-2. This is the first demonstration of mitochondrion-mediated,
      caspase-dependent apoptosis in HHV-6A-infected cells.

PMID- 23554662
TI  - A novel SATB1 binding site in the BCL2 promoter region possesses transcriptional
      regulatory function.
AB  - BCL2 is a key regulator of apoptosis. Our previous work has demonstrated that
      special AT-rich sequence-binding protein 1 (SATB1) is positively correlated with
      BCL2 expression. In the present study, we report a new SATB1 binding site located
      between P1 and P2 promoters of the BCL2 gene. The candidate SATB1 binding
      sequence predicted by bioinformatic analysis was investigated in vitro and in
      vivo by electrophoretic gel mobility shift assays (EMSA) and chromatin
      immunoprecipitation (ChIP). One 25-bp sequence, named SB1, was confirmed to be
      SATB1 binding site. The regulatory function of SB1 and its relevance to SATB1
      were further examed with dual-luciferase reporter assay system in Jurkat cells.
      We found that SB1 could negatively regulate reporter gene activity. Mutation of
      SATB1 binding site further repressed the activity. Knockdown of SATB1 also
      enhanced this negative effect of SB1. Our data indicate that the SB1 sequence
      possesses negative transcriptional regulatory function and this function can be
      antagonized by SATB1.

PMID- 23554663
TI  - Protocol for electrophysiological monitoring of carotid endarterectomies.
AB  - Near zero stroke rates can be achieved in carotid endarterectomy (CEA) surgery
      with selective shunting and electrophysiological neuromonitoring. though false
      negative rates as high as 40% have been reported. We sought to determine if
      improved training for interpretation of the monitoring signals can advance the
      efficacy of selective shunting with electrophysiological monitoring across
      multiple centers, and determine if other factors could contribute to the
      differences in reports. Processed and raw beta band (12.5-30 Hz)
      electroencephalogram (EEG) and median and tibial nerve somatosensory evoked
      potentials (SSEP) were monitored in 668 CEA cases at six surgical centers. A
      decrease in amplitude of 50% or more in any EEG or SSEP channel was the criteria
      for shunting or initiating a neuroprotective protocol. A reduction of 50% or
      greater in the beta band of the EEG or amplitude of the SSEP was observed in 150
      cases. No patient showed signs of a cerebral infarct after surgery. Selective
      shunting based on EEG and SSEP monitoring can reduce CEA intraoperative stroke
      rate to a near zero level if trained personnel adopted standardized protocols. We
      also found that the rapid administration of a protective stroke protocol by
      attending anesthesiologists was an important aspect of this success rate.

PMID- 23554664
TI  - Applications of multislice CT angiography in the surgical clipping and
      endovascular coiling of intracranial aneurysms.
AB  - Prompt diagnosis and therapy of aneurysms are critical for patients with
      nontraumatic subarachnoid hemorrhage (SAH). The aim of our study was to assess
      the clinical usefulness of multislice computed tomography angiography (CTA) in
      the surgical and endovascular treatment of intracranial aneurysms. A total of 195
      cases with 206 intracranial aneurysms underwent CTA. Fifty (24%) aneurysms
      underwent surgical clipping while 156 (76%) aneurysms underwent endovascular
      coiling. In the five missed aneurysms at digital substraction angiography and the
      nine aneurysms with mass intracerebral hematomas, surgical treatment was
      successfully performed based on 16-slice CTA alone, and the other 36 aneurysms
      were clipped on the main basis of the CTA. The intraoperative findings correlated
      well with the CTA findings and all aneurysms were clipped successfully. Sixteen
      slice CTA image information has been shown to determine the choice of aneurysm
      therapy and assist the surgical and endovascular treatment of intracranial
      aneurysms.

PMID- 23554665
TI  - Fracture resistance and pattern of the upper premolars with obturated canals and
      restored endodontic occlusal access cavities.
AB  - We studied whether obturing canals and restoring endodontic occlusal access
      cavities on upper premolars could provide acceptable resistance and pattern to
      fracture. Eighteen upper premolars were divided equally into 3 groups. Group 1
      consisted of intact controls; group 2 had access cavities and root canal
      preparations; group 3 as in group 2 but obturated with gutta-percha and AH26, and
      the access cavity restored with glass ionomer and composite. Specimens were
      submitted to compressive strength testing using the Hounsfield Universal H50KM
      testing machine with a load cell of 2000 Newtons and a crosshead speed set at 1.0
      mm/min until fracture. The results from the compressive strength tests showed
      that intact controls (1105.83+/-90.93 MPa) and restored premolars (936.67+/-44.67
      MPa) were significantly different from premolars with unrestored access cavities
      568.33+/-105.49 MPa. There was no significant difference between intact controls
      and restored premolars. The predominant fracture pattern for intact teeth was an
      oblique fracture. For premolars that had endodontic access cavities, restored or
      unrestored, the most common fracture pattern was a vertical fracture. The
      restoration of occlusal access cavities with glass ionomer and composite provided
      fracture resistance close to that of intact controls, but when restored teeth
      fractured, they were predominantly non-restorable.

PMID- 23554666
TI  - Retrieval of dislodged coronary stent from left renal artery by gooseneck snare.
AB  - A rapamycin-eluting stent was dislodged during attempt of implantation at the
      proximal right coronary artery, which was found by fluoroscopy to have migrated
      into the anterior trunk of the left renal artery. We chose a 5 mm diameter
      Amplatz gooseneck snare and successfully retrieved the lost stent from the
      lodging vessel.

PMID- 23554667
TI  - A survey of HIV infection and related high-risk factors among men who have sex
      with men in Suzhou, Jiangsu, China.
AB  - A cross-sectional study using the snowball sampling method was conducted in May
      2008 to investigate human immunodeficiency virus (HIV) infection status and
      related high risk factors among men who have sex with men (MSM) in Suzhou city of
      Jiangsu province. The researchers carried out a face-to-face questionnaire
      interview among MSM, and collected their blood samples to test for HIV and other
      sexually transmitted diseases (STDs). Among the 280 respondents, 91.1% had
      homosexual acts in the past 6 months and 87.5% had multiple homosexual partners;
      46.4% had heterosexual sex in the past 6 months and 33.1% had multiple
      heterosexual partners. The rate of continued condom use was 44.3% in homosexual
      sex in the past 6 months, while the rate in heterosexual sex was 33.9%.
      Laboratory test results showed that the prevalences of HIV and syphilis were 7.1%
      (20/280) and 15.0% (42/280), respectively, but no HCV-positive person was found.
      In the multivariate logistic regression model, subjects with a monthly income of
      more than RMB Y 1,000 (OR=4.83,95% CI=1.44-16.22), subjects who often went to
      bars for sexual partners (OR=2.25, 95%CI=1.21-4.20), and subjects who had more
      than one sexual partner in the past 6 months (OR=0.49, 95%CI=0.25-0.97) and had
      sex with fixed sexual partners in the past 6 months (OR=0.42, 95%CI=0.25-0.75)
      were significantly associated with the rate of continued condom use in homosexual
      sex in the past 6 months. Unprotected sex and multiple sexual partners were more
      common among MSM in Suzhou city; furthermore, the prevalences of HIV infection
      and syphilis were relatively high. HIV preventive measures should be designed to
      address these risk factors and control the spread of HIV among MSM.

PMID- 23554668
TI  - Association between p53 Pro72Arg polymorphism and prostate cancer risk: a meta
      analysis.
AB  - The tumor suppressor gene p53 appears to be important in the development of many
      human cancers, such as prostate cancer. The association of p53 codon72
      polymorphism with prostate cancer has been widely reported; however, the results
      are inconsistent. To derive a more precise estimation of this relationship, we
      performed an updated meta-analysis from 10 case-control studies. We conducted a
      search in the PubMed database without a language limitation, covering all papers
      published until July 2010. Risk ratios (RR) with 95% confidence intervals (CIs)
      were used to assess the strength of the association. Ten studies including 1,196
      cases and 1,704 controls were selected. Overall, no significant differences of
      total prostate cancer risk and p53 codon polymorphism was found (Pro/Pro vs
      Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, P heterogeneity = 0.016, I (2) = 55.8%;
      Pro/Pro+Pro/Arg vs Arg/Arg, RR = 1.05, 95%CI=1.00-1.11, P heterogeneity = 0.077,
      I (2) = 51.1%). In the stratified analysis by ethnicity, the same results were
      found. However, in the control subgroup, there was a modest decreased association
      between prostate cancer risk and population-based control subjects under the
      recessive genetic model (RR = 0.31, 95%CI=0.10-0.91, P heterogeneity = 0.110, I
      (2) =60.8%). This meta-analysis suggested that p53 codon Pro72Arg polymorphism
      could be weakly associated with prostate cancer risk.

PMID- 23554669
TI  - Tagging single nucleotide polymorphisms in the PPAR-gamma and RXR-alpha gene and
      type 2 diabetes risk: a case-control study of a Chinese Han population.
AB  - Peroxisome proliferator-activated receptor (PPAR-gamma),which is mainly involved
      in adipocyte differentiation, has been suggested to play an important role in the
      pathogenesis of insulin resistance and atherosclerosis. We investigated the
      frequencies of two common tagging polymorphisms of the PPAR-gamma gene and two of
      PPAR-alpha with minor allele frequency (MAF) >=0.05 in the Chinese Han population
      and analyzed the correlation between the different genotypes and the risk of type
      2 diabetes mellitus (T2DM). TaqMan(r) assay was performed to test the genotypes
      in T2DM patients (n = 1,105) and normal controls (n = 1,107). Serum adiponectin
      concentration was measured by ELISA kit. The variant genotypes rs17817276GG,
      rs3856806CT and rs3856806CT/TT of PPAR-gamma were associated with T2DM, P =
      0.023,0.037 and 0.018, respectively. Furthermore, the prevalence of haplotype GT
      in PPAR-gamma was less frequent in the case subjects (0.3%) than in the controls
      (1.9%) [P < 0.001,OR(95%CI)=0.13 (0.06-0.31)]. Patients with genotype TT of
      rs3856806 had a higher serum level of adiponectin than those with the genotype CC
      and CT (P = 0.031 and 0.038, respectively). There was no statistically
      significant difference between patients and controls in genotype distribution of
      rs6537944 and rs1045570 of the RXR-alpha gene. The present study suggests that
      the variant genotypes in the PPAR-gamma gene could decrease the risk for the
      development of T2DM in the Chinese Han population.

PMID- 23554670
TI  - The role of microRNAs during the genesis of medulloblastomas induced by the
      hedgehog pathway.
AB  - Constitutive hedgehog (Hh) signaling is associated with the genesis of
      medulloblastomas (MB). The objective of this study is to identify special
      microRNAs (miRNAs) regulated by the Hh pathway, and to clarify the role of miRNAs
      during the genesis of MB induced by sustained Hh activation. In the primary
      screening, we used stem-loop RT-PCR to test the expression of 90 different miRNAs
      in the wildtype (WT) and Ptc-/- MEF cell lines. In the secondary screening, the
      miRNAs screened from the first screening were validated in the Sufu-/- MEF cell
      lines. We then verified the expression of miRNAs both in the normal cerebellar
      tissues and the MB induced by activated Hh pathway, and examined the expression
      of the other 21 miRNA members of the miR-154 cluster in the MB and normal
      cerebellum. In the first screening, 13 miRNAs showed significant differential
      expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant
      difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum,
      only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and
      normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were
      downregulated in the MB. Our study demonstrated that miR-154 may be regulated by
      the Hh pathway, and the activation of the Hh pathway led to the downregulation of
      the miR-154 cluster, resulting in the genesis of MB.

PMID- 23554671
TI  - A mutation in the type II hair keratin KRT86 gene in a Han family with
      monilethrix.
AB  - Monilethrix, a congenital disease of hair, is usually associated with mutations
      in keratin genes, like KRT81, KRT83 and KRT86. We conducted this study to
      investigate the mutation of type II human basic hair keratin hHb/KRT gene in a
      Han family with monilethrix and obtain information for potential pathogenic
      mechanism study of monilethrix. Peripheral blood samples were drawn for genomic
      DNA detection. Exon 1 and exon 7 of the KRT81, KRT83 and KRT86 genes were
      amplified by PCR. All PCR products were sequenced directly using an ABI 310 DNA
      sequencer. These sequences were aligned with the standard sequences in GenBank
      using the BLAST software. PCR products were digested with restriction
      endonuclease and restriction fragment length polymorphism (RFLP) analysis was
      performed. In this study, we identified one novel mutation, which is a
      heterozygous transitional mutation of G->A at position 1,289 in exon 7 of the
      KRT86 gene [R430Q (KRT86)]. RFLP assays for the novel mutation excluded the
      possibility of polymorphism. The R430Q mutation of the KRT86 gene may be
      pathogenic for monilethrix. Meanwhile, we did not find any novel mutation or
      recurrent mutation in exons 1 and 7 of KRT81 and KRT83 and exon 1 of KRT86. There
      is a potential pathogenic gene in the subjects and our results expand the
      spectrum of mutations in the hHb6 gene.

PMID- 23554672
TI  - Single-dose and multiple-dose pharmacokinetics of zaltoprofen after oral
      administration in healthy Chinese volunteers.
AB  - Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory
      drugs, has strong inhibitory effects on actue and chronic inflammation. A
      randomized, dose-escalating study was conducted to evaluate the pharmacokinetics
      of single and multiple oral doses of zaltoprofen in 12 healthy Chinese
      volunteers. Pharmacokinetics was determined from serial blood samples obtained up
      to 24 h after administration of a single dose of zaltoprofen at 80, 160 or 240 mg
      and after multiple doses of zaltqorofen at 80 mg 3 times daily. The Cmax and AUC0
      24 of zaltoprofen were found to be proportional to drug dose. Zaltoprofen was
      rapidly absorbed (tmax =1.46+/-0.83 h) and cleared (t1/2 =4.96+/-2.97 h).
      Pharmacokinetic parameters after multiple doses were similar to those after
      single doses. Zaltoprofen was well tolerated. These results support a tid regimen
      of zaltoprofen for the management of acute and chronic inflammation.

PMID- 23554673
TI  - Development and optimization of an antibody array method for potential cancer
      biomarker detection.
AB  - Biomarkers play an important role in the detection at an early stage of
      pancreatic cancer. The aim of the present study was to optimize the conditions of
      antibody arrays for detecting Hippocalcin-like 1 (HPCAL1),
      phosphatidylethanolamine binding protein 1 (PEBP1), lectin galactoside-binding
      soluble 7 (LGALS7), and serpin peptidase inhibitor clade E member 2 (SERPINE2) as
      biomarkers for pancreatic cancer detection in a single assay and to investigate
      antibodies' specificity and cross-reactivity. Capture antibodies against HPCAL1,
      PEBP1, LGALS7 and SERPINE2 were printed on nitrocellulose coated glass slides.
      HPCAL1, PEBP1, LGALS7 and SERPINE2 proteins with different concentrations were
      incubated with the capture antibodies at different temperatures for different
      time periods. Biotinylated detection antibodies recognizing a different epitope
      on the captured proteins and a secondary detection molecule (Streptavidin-PE)
      were used to detect fluorescent signals. The arrays showed the strongest signals
      when the concentration of the capture antibodies was at 500 ug/mL in PBST0.05
      (PBS with 0.05% Tween-20), and the slides were incubated overnight at 4 degrees
      C. The lowest protein concentration for detection was 2 ng/mL. Each antibody
      demonstrated high specificity to the corresponding antigen in detecting a mixture
      of 4 proteins without significant cross-reactivity. The fluorescence and
      biomarker concentration displayed a linear correlation. The antibody microarray
      system could be a useful tool for potential biomarker detection for pancreatic
      cancer.

PMID- 23554674
TI  - Successful conservative management with methotrexate and mifepristone of cervical
      pregnancy.
AB  - This study investigated possible effective treatments for cervical pregnancy, a
      rare form of ectopic pregnancy. The clinical records of 11 cases of ectopic
      pregnancy admitted to the Third Affiliated Hospital of Sun Yat-sen University
      from 1998 to 2010 were analyzed. All patients were treated with intermuscular
      injection of methotrexate (MTX, 50 mg), and oral mifepristone (25 mg, bid). All
      cases were successfully cured by conservative treatments using methotrexate plus
      mifepristone. Cervical pregnancy is a contributive factor to mutiple abortions
      and curettages. Methotrexate plus mifepristone, curettage through hysteroscopy
      and intracervical obturation with gauze are effective treatments of cervical
      pregnancy without the need for surgical intervention.

PMID- 23554676
TI  - Pouch Roux-en-Y vs No Pouch Roux-en-Y following total gastrectomy: a meta
      analysis based on 12 studies.
AB  - After a total resection of the stomach, the continuity of the gastrointestinal
      tract can be restored either by Roux-en-Y esophagojejunostomy with or without a
      pouch. There is still no consensus on the best reconstruction technique. The aim
      of this report was to derive a more precise estimation of Roux-en-Y
      esophagojejunostomy with a pouch compared with Roux-en-Y esophagojejunostomy
      without a pouch. Studies were identified by PubMed and Embase searches, and the
      inclusion criteria were randomized controlled trials (RCTs) comparing
      reconstruction techniques between Roux-en-Y with and without a pouch. A total of
      12 studies including 1,018 patients were included. The meta-analysis shows that
      pouch Roux-en-Y does not significantly increase total postoperative
      complications, anastomotic leakage or mortality. Importantly, there is no
      significant difference in 5-year survival rates between the two groups. Patients
      with Roux-en-Y esophagojejunostomy complained significantly less of reflux
      symptoms and dumping syndrome, and had significantly less severe reflux
      esophagitis. Quality of life was significantly improved in patients with Roux-en
      Y esophagojejunostomy with a pouch compared with patients who received Roux-en-Y
      reconstruction without a pouch. The results indicate the need for Roux-en-Y
      esophagojejunostomy with a pouch is a gastric substitute after total gastrectomy
      by comparison with Roux-en-Y esophagojejunostomy without a pouch.

PMID- 23554677
TI  - Corrigendum.

PMID- 23554675
TI  - Gender-based differences in cardiac diseases.
AB  - It has been observed that the incidence of heart failure and Brugada syndrome are
      higher in men, while women are more likely to have QT interval prolongation and
      develop torsades de pointes (TdP). Over the past decade, new studies have
      improved our understanding of the mechanisms of abnormal repolarization and the
      relationship between gender differences in cardiac repolarization and
      presentation of clinical syndromes. Nevertheless, the causes of gender-based
      differences in cardiac disease are still not completely clear. This review paper
      briefly summarized what is currently known about gender differences in heart
      failure, Brugada syndrome and long QT syndrome from molecular mechanisms to
      clinical presentations.

PMID- 23554678
TI  - Comparative domain modeling of human EGF-like module EMR2 and study of
      interaction of the fourth domain of EGF with chondroitin 4-sulphate.
AB  - EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a
      G-protein coupled receptor (G-PCR). Mutation in EMR2 causes complicated disorders
      like polycystic kidney disease (PKD). The structure of EMR2 shows that the fifth
      domain is comprised of EGF-TM7 helices. Functional assignment of EMR2 by support
      vector machine (SVM) revealed that along with transporter activity, several novel
      functions are predicted. A twenty amino acid sequence "MGGRVFLVFLAFCVWLTLPG" acts
      as the signal peptide responsible for posttranslational transport. Eight amino
      acids are involved in N-glycosylation sites and two cleavage sites are Leu517 and
      Ser518 in EMR2. The residue Arg241 is responsible for interaction with
      glycosaminoglycan and chondroitin sulfate. On the basis of structure, function
      and ligand binding sites, competitive EMR2 inhibitors designed may decrease the
      rate of human diseases like Usher's syndrome, bilateral frontoparietal
      polymicrogyria and PKD.

PMID- 23554679
TI  - Fibrinogen-like protein 2 expression correlates with microthrombosis in rats with
      type 2 diabetic nephropathy.
AB  - Fibrinogen-like protein 2 (fgl2), a novel prothrombinase, is involved in
      microthrombosis. We examined fgl2 expression in the glomerular and
      tubulointerstitial capillaries and its correlation with microthromsis in rats
      with streptozocin-induced type 2 diabetic nephropathy. Our RT-PCR and
      immunoblotting analysis showed that fgl2 mRNA and protein levels were increased
      in microvascular endothelial cells of the glomeruli and renal interstitia at week
      19 and became significantly elevated with the development of diabetic nephropathy
      (P < 0.01). Fgl2 was not or only weakly expressed in the renal tissues of normal
      rats. Furthermore, a direct significant correlation (r = 0.543, P < 0.01) was
      found between fgl2 expression and microthrombotic capillaries in the renal
      tissues. Enzyme linked immunosorbent assays (ELISA) additionally showed that
      circulating TNF-alpha levels in rats with type 2 diabetes were significantly
      elevated and closely correlated with fgl2 expression (r = 0.871, P < 0.01). Our
      results suggest that fgl2 may activate renal microthrombosis, thus contributing
      to glomerular hypertension and renal ischemia.

PMID- 23554680
TI  - CASP8 promoter polymorphism, mRNA expression and risk of prostate cancer among
      Chinese men.
AB  - Caspase-8 (CASP8) plays a key role in apoptosis. We examined by genotyping
      whether the -652 six-nucleotide insertion-deletion (6N ins/del) polymorphism in
      the CASP8 promoter region was associated with prostate cancer risk in a hospital
      based case-control study of 406 Chinese prostate cancer patients and 408 age
      matched cancer-free controls. Additionally, 23 prostate cancer tissues were
      analyzed for CASP8 mRNA expression. We found a significantly decreased prostate
      cancer risk for the 6N ins/del genotype [adjusted odds ratio (OR)=0.68; 95%
      confidence interval (CI)=0.51-0.92] and del/del genotype (OR=0.34; 95% CI=0.19
      0.63) compared with the ins/ins genotype. The 6N del allele was associated dose
      dependently with decreased prostate cancer risk (P trend = 0.001). RT-PCR showed
      that individuals with the 6N del allele had lower CASP8 mRNA levels than those
      with the ins/ins genotype (P = 0.024). These findings suggested that the CASP8
      652 6N ins/del polymorphism may affect the susceptibility to prostate cancer and
      reduce prostate cancer risk among Chinese men.

PMID- 23554681
TI  - UVB suppresses PTEN expression by upregulating miR-141 in HaCaT cells.
AB  - MicroRNAs (miRNAs) are 21 to 24 nucleotide, non-coding RNA molecules that post
      transcriptionally regulate the expression of target genes. Ultraviolet B (UVB)
      radiation has been shown to inhibit phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) expression in HaCaT cells through an unknown mechanism. In
      this study, we investigated whether miR-141 can regulate UVB exposure-mediated
      inhibition of PTEN expression. Real-time RT-PCR, annexin V/fluorescein
      isothiocyanate staining, Western blotting and anti-miRNA oligonucleotide
      transfection were employed in this study. We found that upregulation of miR-141
      expression after UVB irradiation was inversely correlated with PTEN expression
      levels in HaCaT cells. Furthermore, miR-141 expression increased apoptosis, while
      anti-miR-141 partly restored PTEN expression and reversed the pro-apoptosis
      effect of UVB. UVB suppresses the expression of PTEN by upregulating miR-141 in
      HaCaT cells. Therefore, miR-141 is a potential gene therapy target for UVB
      induced photodamage.

PMID- 23554682
TI  - mRNA profiles of cytokine receptors in unstimulated peripheral blood mononuclear
      cells from patients with chronic idiopathic urticaria.
AB  - This present study was aimed to investigate the roles of the receptors of Th1/Th2
      cytokines and chemokines in the pathogenesis of chronic idiopathic urticaria
      (CIU). Thirty patients with CIU, 30 patients with dermographism and 30 healthy
      controls were randomly enrolled. Reverse transcription-PCR (RT-PCR) was used to
      analyze the mRNA of cytokine receptors in peripheral blood mononuclear cells
      (PBMCs). The mRNA levels of tumor necrosis factor receptor (TNFR), interferon
      gamma receptor (IFN-gammaR), and interleukin-10 receptor (IL-10R) were
      statistically increased in the CIU group (P < 0.05), while IL-2R, IL-4R, IL-6R,
      and IL-13R showed no significant differences between the CIU and other groups.
      The mRNA levels of CCR3 and CCR6 were statistically increased in the CIU group (P
      < 0.05). The toll-like receptor 2 (TLR2) mRNA level was significantly lower in
      the CIU group than the healthy control group (P < 0.05). These findings indicate
      that the regulation of mRNA of TNFR, IFN-gammaR, IL-10R, CCR3, CCR6 and TLR2 may
      be involved in the pathogenesis of CIU.

PMID- 23554683
TI  - The efficacy of NP11-4-derived immunotoxin scFv-artesunate in reducing hepatic
      fibrosis induced by Schistosoma japonicum in mice.
AB  - Schistosomiasis is one of the most prevalent parasitic diseases in China, and
      hepatic fibrosis caused by schistosome infection is the principal cause of death.
      The aim of this study was to evaluate the efficacy of NP11-4-derived immunotoxin
      scFv-artesunate on Schistosoma japonicum-induced hepatic fibrosis. A single-chain
      variable fragment (scFv) was generated from the murine anti-Schistosoma japonicum
      (S. japanicum) monoclonal antibody NP11-4. The scFv was expressed as a soluble
      protein and purified by Ni-affinity chromatography. After conjugation with
      artesunate, the binding ability with soluble egg antigens (SEA) was determined by
      an enzyme-linked immunosorbent assay (ELISA). The biological activity of purified
      scFv, scFv-artesunate (immunotoxin), and artesunate was detected in vivo. Image
      Pro Plus software was used to analyze the size of egg granuloma and the extent of
      liver fibrosis. The recombinant scFv expession vector was constructed and
      expressed successfully. After purification by a His-trap Ni-affinity column, the
      scFv yield was approximately 0.8 mg/L of culture medium. ELISA results showed
      that chemical conjugation did not affect the binding activity of the immunotoxin.
      Our animal experiments indicated that the immunotoxin could significantly reduce
      the size of egg granuloma in the liver and inhibit hepatic fibrosis. The
      immunotoxin could be used as a promising candidate in the targeted therapy of S.
      japonicum-induced hepatic fibrosis.

PMID- 23554685
TI  - Identification of distant co-evolving residues in antigen 85C from Mycobacterium
      tuberculosis using statistical coupling analysis of the esterase family proteins.
AB  - A fundamental goal in cellular signaling is to understand allosteric
      communication, the process by which signals originating at one site in a protein
      propagate reliably to affect distant functional sites. The general principles of
      protein structure that underlie this process remain unknown. Statistical coupling
      analysis (SCA) is a statistical technique that uses evolutionary data of a
      protein family to measure correlation between distant functional sites and
      suggests allosteric communication. In proteins, very distant and small
      interactions between collections of amino acids provide the communication which
      can be important for signaling process. In this paper, we present the SCA of
      protein alignment of the esterase family (pfam ID: PF00756) containing the
      sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a
      subset of interacting residues. Clustering analysis of the pairwise correlation
      highlighted seven important residue positions in the esterase family alignments.
      These residues were then mapped on the crystal structure of antigen 85C (PDB ID:
      1DQZ). The mapping revealed correlation between 3 distant residues (Asp38, Leu123
      and Met125) and suggests allosteric communication between them. This information
      can be used for a new drug against this fatal disease.

PMID- 23554684
TI  - Genetic susceptibility of cervical cancer.
AB  - Epidemiological and laboratory-based studies have identified infection with one
      of 15 high-risk human papillomavirus (HPV) types as a necessary but not
      sufficient cause of cervical cancer. The prevalence of genital HPV infections is
      high in young women, but most of the infections regress without interventions.
      Host genetic variations in genes involved in immune response pathways may be
      related to HPV clearance, and HPV E6/E7 oncoproteins interacting or downstream
      genes, both coding and non-coding, may contribute to the outcome of high risk HPV
      infection and cervical cancer. Of specific interest for this review has been the
      selection of genetic variants in genes involved in the above-referred pathways
      with a summary of their applications in association studies. Because the
      supportive and opposing data have been reported in different populations, well
      designed international collaborative studies need to be conducted to define the
      consistency of the associations, paving the way to better define the patients at
      high risk of developing cervical cancer.

PMID- 23554686
TI  - MiR-148a inhibits angiogenesis by targeting ERBB3.
AB  - MicroRNAs (miRNAs) play an important role in carcinogenesis in various solid
      cancers including breast cancer. Down-regulation of microRNA-148a (miR-148a) has
      been reported in certain cancer types. However, the biological role of miR-148a
      and its related targets in breast cancer are unknown yet. In this study, we
      showed that the level of miR-148a was lower in MCF7 cells than that in MCF10A
      cells. V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) is a
      direct target of miR-148a in human breast cancer cells through direct binding of
      miR-148a to ERBB3 3'-UTR region. Overexpression of miR-148a in MCF7 cells
      inhibited ERBB3 expression, blocked the downstream pathway activation including
      activation of AKT, ERK1/2, and p70S6K1, and decreased HIF-1alpha expression.
      Furthermore, forced expression of miR-148a attenuated tumor angiogenesis in vivo.
      Our results identify ERBB3 as a direct target of miR-148a, and provide direct
      evidence that miR-148a inhibits tumor angiogenesis through ERBB3 and its
      downstream signaling molecules. This information would be helpful for targeting
      the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the
      future.

PMID- 23554687
TI  - TLR2 was overexpressed independent of IL-6 in patients with valvular atrial
      fibrillation.
AB  - Toll-like receptor 2 (TLR2) has recently been shown to be up-regulated in
      patients with non-valvular atrial fibrillation (AF). The present study was aimed
      to determine whether the pathogenesis and development of AF is associated with
      the up-regulation of TLR2. Clinical data and right atrial appendage (RAA)
      specimens were collected from 20 patients with persisten AF (PeAF), 15 patients
      with paroxysmal AF (PaAF) and 13 patients with no history of AF undergoing
      valvular replacement. The results showed that gene expression and protein content
      of TLR2 were increased in both the AF subgroups, compared with the sinus rhythm
      (SR) group. Between the two AF subgroups, PaAF had a higher TLR2 level than PeAF.
      However, no difference in interluekin (IL)-6 content was found among the three
      groups, and no correlation was found between TLR2 and IL-6 in PeAF patients (r =
      0.090, P = 0.706), PaAF patients (r = 0.408, P = 0.131) and AF patients (r = 
      0.301, P = 0.079). Immunohistochemical analysis revealed that TLR2 was
      distributed in RAAs of AF patients and confirmed the immunoblotting results. In
      conclusion, we demonstrated that TLR2 was elevated in AF (especially PaAF)
      patients with valvular heart disease, further implicating inflammation involved
      in the pathogenesis and development of AF.

PMID- 23554688
TI  - Crystalloid and colloid preload for maintaining cardiac output in elderly
      patients undergoing total hip replacement under spinal anesthesia.
AB  - The aim of the present study was to compare the effects of colloid and
      crystalloid preload on cardiac output (CO) and incidence of hypotension in
      elderly patients under spinal anesthesia (SA). A randomized, double-blinded study
      was conducted including 47 elderly patients undergoing scheduled total hip
      replacement (THR), who were randomized to three groups: the control group (C
      group, n = 15), crystalloid (RS group, n =16) and colloid group (HES group, n =
      16). An intravenous preload of 8 mL/kg of either lactated Ringer's solution in
      the RS group or 6% hydroxyethyl starch in the HES group was infused within 20 min
      before SA induction, while no intravenous preload was given in the C group. There
      was a trend of decrease in CO and systolic blood pressure after SA with time in
      the C group. In the RS and HES groups, CO increased significantly after fluid
      preloading as compared with baseline (P < 0.01). Thereafter, CO remained higher
      than baseline until 30 min after SA in the HES group. The change of systolic
      blood pressure was similar to CO, but no significant difference from baseline was
      observed in each group. Hypotension occurred in 3 patients in the C group and one
      each in the RS and HES group, respectively (P = 0.362). Intravascular volume
      preload with colloid is more effective than crystalloid solution in maintaining
      CO, which may be improved the hemodynamic stability in elderly patients during
      SA.

PMID- 23554689
TI  - Effects of infusion of different fluids during controlled hypotension on gastric
      intramucosal pH and postoperative gastroenterological function.
AB  - The present study was aimed to investigate the effects of infusion of different
      fluids combined with controlled hypotension on gastric intramucosal pH (pHi) and
      postoperative gastrointestinal function in patients undergoing hepatocarcinoma
      surgery. Forty-five patients (ASA II) scheduled for surgical resection of
      hepatocarcinoma undergoing controlled hypotension were randomly assigned to three
      groups and received infusion of 20 mL/kg Ringer's solution (R group), 6% HAES(H
      group) or 6% Voluven group (W group). Intragastric PgCO2, pHi, hematocrit and
      hemoglobin were measured. The significant decrease of pHi and increase of PgCO2
      were produced at 1 and 2 h after controlled hypotension in the R group (P < 0.05
      or P < 0.01). The time of bowel movement after operation was shorter in the W
      group than the R group. Meanwhile, we also did not find obvious difference in
      blood gas indexes among the three groups. The infusion of HAES and Voluven during
      controlled hypotension could improve gastrointestinal perfusion and accelerate
      the recovery of postoperative gastrointestinal function.

PMID- 23554690
TI  - Apparent diffusion coefficient in normal and abnormal pattern of intervertebral
      lumbar discs: initial experience.
AB  - The aim of the present study was to compare the relationship of morphologically
      defined non-bulging/herniated, bulging and herniated intervertebral lumbar discs
      with quantitative apparent diffusion coefficient (ADC). Thirty-two healthy
      volunteers and 28 patients with back pain or sciatica were examined by MRI. All
      intervertebral lumbar discs from L1 to S1 were classified according to
      morphological abnormality and degenerated grades. The ADC values of nucleus
      pulposus (NP) were measured and recorded. The significant differences about mean
      ADC values of NP were found between non-bulging/herniated discs and bulging discs
      as well as herniated discs (P < 0.05), whereas there were no significant
      differences in ADC values between bulging and herniated discs (P > 0.05).
      Moreover, statistically significant relationship was found in the mean ADC values
      of NP between "non-bulging/herniated and non-degenerated discs" and "non
      bulging/herniated degenerated discs" as well as herniated discs (P < 0.05).
      Linear regression analysis between ADC value and disc level revealed an inverse
      correlation (r = -0.18). The ADC map of the NP is a potentially useful tool for
      the quantitative assessment of componential and molecular alterations accompanied
      with lumbar disc abnormalities.

PMID- 23554691
TI  - Hypoxic response elements and Tet-On advanced double-controlled systems regulate
      hVEGF 165 and angiopoietin-1 gene expression in vitro.
AB  - Angiogenesis in ischemic tissue is a complex and multi-gene event. In the study,
      we constructed hypoxic response elements (HRE) and the Tet-On advanced double
      controlled systems and investigated their effects on the expression of hVEGF165
      and angiopoietin-1 (Ang-1) genes in rat cardiomyocytes exposed to hypoxia and
      pharmacologic induction. We infected neonatal rat cardiomyocytes with recombinant
      rAAV-rtTA-Rs-M2/rAAV-TRE-Tight-Ang-1 and rAAV-9HRE- hVEGF165. Our results
      indicated that the viral titer was 1*10(12) vg /mL and the viral purity exceeded
      98%. hVEGF 165 expression was induced by hypoxia, but not by normoxia (P <
      0.001). Ang-1 expression was evident under doxycycline induction, but
      undetectable without doxycycline induction (P < 0.001). Immunofluorescence
      staining showed that positively stained hVEGF165 and Ang-1 protein appeared only
      under both hypoxia and doxycycline induction. We demonstrate here that HRE and
      the recombinant Tet-On advanced double gene-controlled systems sensitively
      regulate the expression of hVEGF165 and Ang-1 genes in an altered oxygen
      environment and under pharmacological induction in vitro.

PMID- 23554692
TI  - A novel bead-based fluorescence immunoassay for aldosterone.
AB  - Aldosterone quantification helps evaluate the rennin-angiotensin-aldosterone
      system. The new bead-based multiplex platform has not been applied in aldosterone
      detection to achieve simultaneous measurements of multiple hormones. A new
      sensitive competitive bead immunoassay based on Luminex technology for detecting
      aldosterone in small sample volumes was developed using two-antibody coupled
      beads and biotinylated aldosterone as tracer in combination with an extraction
      step. The assay was validated in human and mouse samples and exhibited a linear
      working range from 10 to 1,000 pg/mL. The assay was reproducible and precise with
      intra-assay coefficient of variations (CVs) from 6.0% to 11.2%, inter-assay CVs
      from 8.0% to 13.0% and good recovery [(90-110)%] and linearity [(89-107)%].
      Excellent correlation was found between this new assay and the reference method
      (r = 0.96, P < 0.000,1). The successful establishment of this assay provides high
      possibility for carrying out bead-based multiplex assay measuring aldosterone and
      other parameters simultaneously in one 50 uL sample so that the efficiency can be
      improved and precious samples can be saved.

PMID- 23554693
TI  - Surgical repair of thoracoabdominal aortic aneurysms using the critical artery
      reattachment technique.
AB  - In the study, we sought to retrospectively analyze the effectiveness and safety
      of surgical repair of thoracoabdominal aortic aneurysm using the critical artery
      reattachment technique. Twenty-three consecutive thoracoabdominal aortic aneurysm
      patients were treated using the technique of sequential aortic clamping and
      critical artery reattachment. The entire procedure was technically successful in
      all patients. One died of renal failure and the overall hospital mortality was
      4.35%. The total incidence of complications was 21.74%. At a median follow-up of
      33 months, all patients were alive. We found that the application of critical
      artery reattachment technique in the management of thoracoabdominal aortic
      aneurysm provides excellent short- and mid-term results in most patients. It
      could markedly increase the curing rate and reduce the morbidity of postoperative
      complications including paraplegia, ischemia of abdominal viscera, and renal
      failure.

PMID- 23554694
TI  - Anisocoria in a 10-month old girl in the immediate preoperative setting: can you
      proceed with surgery?
AB  - We report the case of a 10-month old girl with a significant past medical history
      who presented for elective surgery with a new-onset fixed, dilated pupil. We
      briefly review the diagnostic approach to such patients and provide guidelines
      for managing these patients in the immediate preoperative setting.

PMID- 23554696
TI  - Activation of Rac1-PI3K/Akt is required for epidermal growth factor-induced PAK1
      activation and cell migration in MDA-MB-231 breast cancer cells.
AB  - Epidermal growth factor (EGF) may increase cell motility, an event implicated in
      cancer cell invasion and metastasis. However, the underlying mechanisms for EGF
      induced cell motility remain elusive. In this study, we found that EGF treatment
      could activate Ras-related C3 botulinum toxin substrate 1 (Rac1), PI3K/Akt and
      p21-actived kinase (PAK1) along with cell migration. Ectopic expression of PAK1
      K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell
      migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably
      inhibited both EGF-induced PAK1 activation and cell migration. Furthermore,
      expression of dominant-negative Rac1 (T17N) could largely block EGF-induced
      PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a
      significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which
      abolished the EGF-induced ROS generation, cell migration, as well as activation
      of PI3K/Akt and PAK, but not Rac1. Our study demonstrated that EGF-induced cell
      migration involves a cascade of signalling events, including activation of Rac1,
      generation of ROS and subsequent activation of PI3K/Akt and PAK1.

PMID- 23554695
TI  - The role of intracellular protein O-glycosylation in cell adhesion and disease.
AB  - Post-translational protein modification, including phosphorylation, is generally
      quick and reversible, facilitating rapid biologic adjustments to altered cellular
      physiologic demands. In addition to protein phosphorylation, other post
      translational modifications have been identified. Intracellular protein O
      glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine (O
      GlcNAc) to serine/threonine residues, is a relatively recently identified post
      translational modification that has added to the complexity by which protein
      function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O
      GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine
      and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes,
      transcription factors, receptors and structural proteins have been shown to be
      modified by intracellular O-glycosylation. In this review, the mechanism and
      relevance of O-GlcNAc protein modification are discussed in the context of cell
      adhesion and several representative diseases.

PMID- 23554697
TI  - Aspirin suppresses growth of human gastric carcinoma cell by inhibiting survivin
      expression.
AB  - Regular use of aspirin (ASA) could reduce the risk of gastric cancer although the
      precise mechanism remains unclear. Down-regulation of survivin may be one of the
      cyclooxygenase-independent mechanisms whereby ASA induces apoptosis of gastric
      cancer cell. In this study, we investigated the effect of ASA on the growth,
      apoptosis and survivin expression of gastric cancer cell line SGC7901. The
      survival of cells treated with 3.0 and 10.0 mmol/L ASA for 24 h was decreased by
      44.6% and 88.5%, respectively. ASA at 3.0 mmol/L inhibited the viability of
      SGC7901 cells in a time-dependent manner. Apoptosis analysis showed similar
      results with MTT assay. ASA at 3.0 and 10.0 mmol/L decreased the mRNA transcript
      levels of survivin and reduced survivin protein levels in SGC7901 cells also in a
      time-dependent manner. Our findings indicated that ASA inhibited the
      proliferation of SGC7901 by suppressing survivin at both the transcriptional and
      translational level.

PMID- 23554698
TI  - Effect of water storage on fluoride release and mechanical properties of a
      polyacid-modified composite resin (compomer).
AB  - We evaluated the effect of water storage on fluoride release and mechanical
      properties of compomer restorative material. Fluoride release was recorded using
      a specific fluoride electrode. Flexural properties and fracture toughness were
      measured using a universal testing machine. Vickers hardness was measured using a
      micro-hardness tester. There was initial burst of fluoride release up to 1 w,
      which was diminished to a low level in 1 mon and remained relatively constant
      over 6 mon. Flexural strength and hardness were increased up to 1 mon followed by
      a gradual decrease up to 6 mon. Flexural modulus was decreased gradually up to 6
      mon. Fracture toughness was increased during the first week and gradually
      decreased over the storage period. We concluded that flexural properties,
      fracture toughness, Vickers hardness and fluoride release of compomer were
      sensitive to water as well as storage time. There was a significant effect of
      fluoride release on the studied mechanical properties.

PMID- 23554699
TI  - Localization of epileptic foci in Children with childhood absence epilepsy by
      magnetoencephalography combined with synthetic aperture magnetometry.
AB  - This present study was aimed to investigate the localizable diagnostic value of
      magnetoencephalography (MEG) combined with synthetic aperture magnetometry (SAM)
      in childhood absence epilepsy (CAE). Thirteen CAE patients underwent MEG
      detection at resting state and after hyperventilation, and then the epileptic
      foci were located by SAM. In the thirteen CAE patients, epileptic foci were found
      in five cases (38.5%), and they were all located in the bilateral frontal lobe,
      suggesting that the frontal lobe in some CAE patients may serve as the epileptic
      foci. Our findings indicate that MEG combined with SAM could be of diagnostic
      value in localizing the epileptic foci in certain CAE patients.

PMID- 23554700
TI  - ApoB/apoA1 is an effective predictor of coronary heart disease risk in overweight
      and obesity.
AB  - We investigated the relationship of apoB/apoA1 ratio and coronary heart disease
      (CHD) in persons who were overweight or obese. The subjects were divided by the
      body mass indexes (BMI) into the normal weight group (n=397, BMI<24 kg/m(2)) and
      the overweight group (n=400, BMI>24 kg/m(2)). Our results showed that the over
      weight group had higher blood pressure [(130.15+/-19.01) mmHg vs (123.66+/-18.70)
      mmHg] and higher levels of blood sugar [(7.09+/-2.89) mmol/L vs (6.21+/-2.59)
      mmol/L], triglyceride [(1.93+/-1.19) mmol/L vs (1.44+/-0.85) mmol/L], total
      cholesterol [(4.26+/-1.06) mmol/L vs (4.09+/-0.99) mmol/L], low-density
      lipoprotein cholesterol (LDL-C) [(2.56+/-0.75) mmol/L vs (2.39+/-0.72) mmol/L],
      and apoB [(0.83+/-0.27) mg/L vs (0.78+/-0.23) mg/L], and a higher apoB/apoA1
      ratio (0.83+/-0.27 vs 0.75+/-0.25) and lower levels high-density lipoprotein
      cholesterol [(1.10+/-0.26) mmol/L vs (1.21+/-0.31) mmol/L] and apoA1 [(1.04+/
      0.20) mg/L vs (1.08+/-0.22) mg/L] than those of the normal weight group (all P <
      0.05). The prevalence of CHD in the over-weight group in the lowest LDL quartile
      was almost twice greater than that of the highest apoB/apoA1 quartile, compared
      with the subjects in the lowest apoB/apoA1 quartile. The higher apoB/apoA1
      quartile was in agreement with the higher prevalence of CHD. In the overweight
      and obesity group, the area under ROC curve (AUC) was the highest for apoB/apoA1
      (0.655). The cut-off point of apoB/apoA1 for optimal sensitivity and specificity
      was at 0.80, with a sensitivity of 57.19% and a specificity of 71.72%. In
      conclusion, apoB and apoA1 were simple clinical indicators, and the apoB/apoA1
      ratio was closely related with CHD in overweight and obese patients. The
      apoB/apoA1 ratio may provide some useful information in the differential
      diagnosis.

PMID- 23554701
TI  - Bisoprolol reverses down-regulation of potassium channel proteins in ventricular
      tissues of rabbits with heart failure.
AB  - Remodeling of ion channels is an important mechanism of arrhythmia induced by
      heart failure (HF). We investigated the expression of potassium channel encoding
      genes in the ventricles of rabbit established by volume-overload operation
      followed with pressure-overload. The reversible effect of these changes with
      bisoprolol was also evaluated. The HF group exhibited left ventricular
      enlargement, systolic dysfunction, prolongation of corrected QT interval (QTc),
      and increased plasma brain natriuretic peptide levels in the HF rabbits. Several
      potassium channel subunit encoding genes were consistently down-regulated in the
      HF rabbits. After bisoprolol treatment, heart function was improved significantly
      and QTc was shortened. Additionally, the mRNA expression of potassium channel
      subunit genes could be partially reversed. The down-regulated expression of
      potassium channel subunits Kv4.3, Kv1.4, KvLQT1, minK and Kir 2.1 may contribute
      to the prolongation of action potential duration in the heart of rabbits induced
      by volume combined with pressure overload HF. Bisoprolol could partially reverse
      these down-regulations and improve heart function.

PMID- 23554702
TI  - Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.)
      Miers in calcium chloride-induced cardiac arrhythmia in rats.
AB  - The present study investigated the antiarrhythmic activity of alcoholic extract
      of Tinospora cordifolia (T. cordifolia) in CaCl2 induced arrhythmia. CaCl2 (25
      mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in
      rats. The animals were then treated with T. cordifolia extract (150, 250, and 450
      mg/kg) and verapamil (5 mg/kg,iv). Lead II electrocardiogram was monitored.
      Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced
      arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and
      450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively,
      and verapamil reduced the heart rate by 9.70% compared to the normal group. The
      PQRST waves were normalized and atrial and ventricular fibrillation was
      controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased
      calcium and sodium levels and decreased potassium levels in blood. T. cordifolia
      dose-dependently decreased calcium and sodium levels and increased potassium
      levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and
      beneficial in atrial and ventricular fibrillation and flutter and may be
      indicated in ventricular tachyarrhythmia.

PMID- 23554703
TI  - Relationship between nerve injury-induced protein gene 2 polymorphism and stroke
      in Chinese Han population.
AB  - The aim of present study was to investigate the relationship between nerve injury
      induced protein 2 (NINJ2) gene polymorphism and stroke in Chinese Han population.
      Fifty-two patients with large-artery atherosclerosis (LAA) infarction, 85
      patients with small-artery occlusion lacunar (SAO) infarction, 50 patients with
      intracerebral hemorrhage (ICH) and 66 controls were included. Genotypes and
      alleles frequencies of the two single nucleotide polymorphisms (SNPs) of NINJ2
      among different groups were analyzed and compared. In regard to rs12425791, the
      frequencies of the AG and AA+AG genotypes of the LAA and SAO groups were
      significantly higher than those in the control group; the frequency of the A
      allele of the SAO group was significantly higher than that of the control group.
      In regard to rs11833579, there were not any significant differences between the
      case and the control groups. The SNP rs12425791 is significantly associated with
      ischemic stroke, and the A allele increases the susceptibility to stroke. The SNP
      rs11833579 is not significantly associated with stroke.

PMID- 23554704
TI  - Effects of minocycline on the expression of NGF and HSP70 and its neuroprotection
      role following intracerebral hemorrhage in rats.
AB  - The present study was aimed to investigate the effects of minocycline (MC) on the
      expression of nerve growth factor (NGF) and heat shock protein 70 (HSP70)
      following intracerebral hemorrhage (ICH) in rats, and explore the neuroprotective
      function of MC. Seventy-eight male SD rats were randomly assigned to three
      groups: the ICH control group (n = 36), ICH intervention group (n = 36) and sham
      operation group (n = 6). The ICH control group and ICH intervention group were
      subdivided into 6 subgroups at 1, 2, 4, 5, 7 and 14 d after ICH with 6 rats in
      each subgroup. Type IV collagenase was injected into the basal nuclei to
      establish the ICH model. All rats showed symptoms of the nervous system after the
      model was established, and the sympotsm in the ICH control group were more
      serious than the ICH intervention group. The number of NGF-positive cells and
      HSP70-positive cells in the ICH intervention group was higher than that of the
      ICH control group. MC administration by intraperitoneal injection can increase
      the expression of NGF and HSP70. MC may inhibit the activation of microglia, the
      inflammatory reaction and factors, matrix metalloproteinases and apoptosis, thus
      protecting neurons. The change of the expression of NGF and HSP70 may be involved
      in the pathway of neuroprotection by MC.

PMID- 23554706
TI  - Molecular screening of patients with nonsyndromic hearing loss from Nanjing city
      of China.
AB  - Hearing loss is the most frequent sensory disorder involving a multitude of
      factors, and at least 50% of cases are due to genetic etiology. To further
      characterize the molecular etiology of hearing loss in the Chinese population, we
      recruited a total of 135 unrelated patients with nonsyndromic sensorineural
      hearing loss (NSHL) for mutational screening of GJB2, GJB3, GJB6, SLC26A4,
      SLC26A5 IVS2-2A>G and mitochondrial 12SrRNA, tRNA(Ser(UCN)) by PCR amplification
      and direct DNA sequencing. The carrier frequencies of deafness-causing mutations
      in these patients were 35.55% in GJB2, 3.70% in GJB6, 15.56% in SLC26A4 and 8.14%
      in mitochondrial 12SrRNA, respectively. The results indicate the necessity of
      genetic screening for mutations of these causative genes in Chinese population
      with nonsyndromic hearing loss.

PMID- 23554707
TI  - Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and
      risk of ischemic stroke in Han Chinese of eastern China.
AB  - Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene
      have been suggested to play an important role in the pathogenesis of
      atherosclerosis and ischemic stroke. This study was aimed to explore the
      association of ALOX5AP variants with ischemic stroke risk in Han Chinese of
      eastern China. A total of 690 ischemic stroke cases and 767 controls were
      recruited. The subjects were further subtyped according to the Trial of Org 10172
      in Acute Stroke Treatment (TOAST) criteria. On the basis of that, two
      polymorphisms of the ALOX5AP gene (rs10507391 and rs12429692) were determined by
      TaqMan genotyping assay. In addition, plasma leukotriene B4 (LTB4) levels were
      analyzed in these subjects. There was no evidence of association between the two
      variants of ALOX5AP and the risk of ischemic stroke or its TOAST-subtypes.
      Haplotype analysis and stratification analysis according to sex, age, body mass
      index, hypertension, and diabetes also showed negative association. Analysis of
      LTB4 levels in a subset of cases and controls revealed that LTB4 levels were
      significantly higher in ischemic stroke cases than in the controls (70.06+/-14.75
      ng/L vs 57.34+/-10.93 ng/L; P = 0.000) and carriers of the T allele of the
      rs10507391 variant were associated with higher plasma LTB4 levels (P = 0.000).
      The present study suggests there is no association of the two polymorphisms in
      the ALOX5AP gene with ischemic stroke risk in Han Chinese of eastern China.

PMID- 23554708
TI  - The distribution of HLA-A, -B, and -DRB1 alleles and haplotypes in inhabitants of
      Guizhou Province of China.
AB  - The present study was aimed to analyze the frequencies of human leukocyte antigen
      (HLA)-A, -B, and -DRB1 alleles and A-B-DRB1, A-B, A-DRB1 and B-DRB1 haplotypes in
      inhabitants of Guizhou province, China. All samples were typed in the HLA-A,-B,
      and -DRB1 loci using the polymerase chain reaction-reverse sequence specific
      oligonucleotide probe (PCR-rSSOP) method and HLA polymorphisms were analyzed. A
      total of 18 HLA-A, 31 HLA-B, and 13 HLA-DRB1 alleles were found in the Guizhou
      population. The first two frequent alleles in the HLA-A, -B, and -DRB1 loci were
      A*11(30.72%) and A*02(30.65%), B*40(16.27%) and B*46(16.27%), and DRB1*09(15.91%)
      and DRB1*15(13.51%), respectively. The most common haplotype was A*02-B*46
      DRB1*09(5.59%) in A-B-DRB1, A*02-B*46(11.73%) in A-B, B*46-DRB1*09(7.49%) in B
      DRB1, and A*02-DRB1*09(8.08%) in A-DRB1. Some haplotypes with strong linkage
      disequilibrium (LD) were found not only in the common haplotypes, such as A*33
      B*58, B*30-DRB1*07, and B*33-DRB1*03, but also in the rare haplotypes, such as
      A*01-B*37, B*37-DRB1*10, and A*01-DRB1*10. Guizhou inhabitants shared some
      characteristics of the Southern Chinese population but also had their own unique
      features. Overall, HLA polymorphism in Guizhou population was more consistent
      with that of Chengdu population than that of other populations in China.

PMID- 23554705
TI  - Competitive metabolism of L-arginine: arginase as a therapeutic target in asthma.
AB  - Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung
      concentrations of NO and its amino acid precursor, L-arginine, are regulated by
      the relative expressions of the NO synthase (NOS) and arginase isoforms.
      Increased expression of arginase I and NOS2 occurs in murine models of allergic
      asthma and in biopsies of asthmatic airways. Although clinical trials involving
      the inhibition of NO-producing enzymes have shown mixed results, small molecule
      arginase inhibitors have shown potential as a therapeutic intervention in animal
      and cell culture models. Their transition to clinical trials is hampered by
      concerns regarding their safety and potential toxicity. In this review, we
      discuss the paradigm of arginase and NOS competition for their substrate L
      arginine in the asthmatic airway. We address the functional role of L-arginine in
      inflammation and the potential role of arginase inhibitors as therapeutics.

PMID- 23554709
TI  - Computational interaction analysis of organophosphorus pesticides with different
      metabolic proteins in humans.
AB  - Pesticides have the potential to leave harmful effects on humans, animals, other
      living organisms, and the environment. Several human metabolic proteins inhibited
      after exposure to organophosphorus pesticides absorbed through the skin,
      inhalation, eyes and oral mucosa, are most important targets for this interaction
      study. The crystal structure of five different proteins, PDBIDs: 3LII, 3NXU,
      4GTU, 2XJ1 and 1YXA in Homo sapiens (H. sapiens), interact with organophosphorus
      pesticides at the molecular level. The 3-D structures were found to be of good
      quality and validated through PROCHECK, ERRAT and ProSA servers. The results show
      that the binding energy is maximum -45.21 relative units of cytochrome P450
      protein with phosmet pesticide. In terms of H-bonding, methyl parathion and
      parathion with acetylcholinesterase protein, parathion, methylparathion and
      phosmet with protein kinase C show the highest interaction. We conclude that
      these organophosphorus pesticides are more toxic and inhibit enzymatic activity
      by interrupting the metabolic pathways in H. sapiens.

PMID- 23554710
TI  - Attribution retraining group therapy for outpatients with major depression
      disorder, generalized anxiety disorder, and obsessive-compulsive disorder: a
      pilot study.
AB  - The aim of this present study is to examine the efficacy of attribution
      retraining group therapy (ARGT) and to compare the responses of outpatients with
      major depression disorder (MDD), generalized anxiety disorder (GAD) and obsessive
      compulsive disorder (OCD). We carried out a prospective uncontrolled intervention
      study with a 8-weeks of ARGT on sixty three outpatients with MDD, GAD or OCD.
      Hamilton rating scale for depression, Hamilton rating scale for anxiety, Yale
      Brown obsessive-compulsive scale, attribution style questionnaire, self-esteem
      scale, index of well-being, and social disability screening schedule were
      administered before and after treatment. Significant improvement in symptoms and
      psychological and social functions from pre- to posttreatment occurred for all
      participants. The changes favored MDD patients. Our study suggested that ARGT may
      improve the symptoms and psychological-social functions of MDD, GAD, and OCD
      patients. MDD patients showed the best response.

PMID- 23554711
TI  - Preoperative administration of intramuscular dezocine reduces postoperative pain
      for laparoscopic cholecystectomy.
AB  - Postoperative pain is the most common complaint after laparoscopic
      cholecystectomy. This study was carried out to evaluate whether preoperative
      administration of intramuscular dezocine can provide postoperative analgesia and
      reduce postoperative opioid consumption in patients undergoing laparoscopic
      cholecystectomy. Patients (ASA I or II) scheduled for laparoscopic
      cholecystectomy were randomly assigned into intramuscular dezocine group (group
      1) or intramuscular normal saline group (group 2). Dezocine and equal volume
      normal saline were administered intramuscularly 10 min before the induction of
      anesthesia. After operation, the severity of postoperative pain, postoperative
      fentanyl requirement, incidence and severity of side-effects were assessed.
      Postoperative pain and postoperative patient-controlled fentanyl consumption were
      reduced significantly in group 1 compared with group 2. The incidence and
      severity of side effects were similar between the two groups. Preoperative single
      dose administration of intramuscular dezocine 0.1 mg/kg was effective in reducing
      postoperative pain and postoperative patient-controlled fentanyl requirement in
      patients undergoing laparoscopic cholecystectomy.

PMID- 23554712
TI  - Comparison of liquid-liquid extraction-thin layer chromatography with solid-phase
      extraction-high-performance thin layer chromatography in detection of urinary
      morphine.
AB  - Liquid-liquid extraction-thin layer chromatography (LLE-TLC) has been a common
      and routine combined method for detection of drugs in biological materials. Solid
      phase extraction (SPE) is gradually replacing the traditional LLE method. High
      performance thin layer chromatography (HPTLC) has several advantages over TLC.
      The present work studied the higher efficiency of a new SPE-HPTLC method over
      that of a routine LLE-TLC method, in extraction and detection of urinary
      morphine. Fifty-eight urine samples, primarily identified as morphine-positive
      samples by a strip test, were re-screened by LLE-TLC and SPE-HPTLC. The results
      of LLE-TLC and SPE-HPTLC were then compared with each other. The results showed
      that the SPE-HPTLC detected 74% of total samples as morphine-positive samples
      whereas the LLE-TLC detected 48% of the same samples. We further discussed the
      effect of codeine abuse on TLC analysis of urinary morphine. Regarding the
      importance of morphine detection in urine, the present combined SPE-HPTLC method
      is suggested as a replacement method for detection of urinary morphine by many
      reference laboratories.

PMID- 23554713
TI  - Familial cardiac myxoma with multifocal recurrences: a case report and review of
      the literature.
AB  - We report a case of myxoma with multiple recurrences in both the atrium and
      ventricle in a 26-year-old woman five years after the surgical removal of left
      atrial myxoma. Her 52-year-old mother had a similar medical history. To our
      knowledge, this was the first familial case who suffered multifocal cardiac
      myxoma recurrences without any sign of the myxoma complex. Based on our
      understanding of the mechanism of recurrence, the approaches to prevent the
      recurrence, and markers to predict recurrence, we propose that multifocal
      recurrences, as reported herein, may result from a combination of familial
      predisposition and multifocal onset. The bi-atrial surgical approach and
      transesophageal echocardiography are preferred for patients with recurrent
      cardiac myxomas, especially for those with multiple recurrences and familial
      myxoma. Immunological and genetic screenings may help to identify family members
      at risk for developing this disease.

PMID- 23554715
TI  - Efficacy and tolerance of tacrolimus and pimecrolimus for atopic dermatitis: a
      meta-analysis.
AB  - Tacrolimus ointment and pimecrolimus cream have proved to be suitable for the
      treatment of atopic dermatitis. We conducted a meta-analysis of the efficacy,
      adverse events/withdrawal of tacrolimus versus pimecrolimus in the treatment of
      atopic dermatitis. According to our meta-analysis, 0.1% tacrolimus was more
      effective than 1% pimecrolimus in the treatment of adult patients and moderate to
      very severe pediatric patients, and more 0.1% mild pediatric patients treatal
      with pimecrolimus withdrew from the trials because of a lack of efficacy or the
      occurrence of adverse events, compared with mild pediatric patients treated with
      0.03% tacrolimus. The combined analyses of tacrolimus with pimecrolimus showed
      that tacrolimus was more effective than pimecrolimus (week 3: RR=0.67, 95%CI=0.56
      0.80; week 6/end of study: RR=0.65, 95%CI=0.57-0.75), and fewer tacrolimus
      treated patients withdrew because of a lack of efficacy (RR=0.32, 95CI%=0.19
      0.53) or the occurrence of adverse events (RR=0.43, 95%CI=0.24-0.75), compared
      with pimecrolimus-treated patients. In conclusion, tacrolimus has higher efficacy
      and better tolerance than pimecrolimus in the treatment of atopic dermatitis.

PMID- 23554714
TI  - Role of remote sensing, geographical information system (GIS) and bioinformatics
      in kala-azar epidemiology.
AB  - Visceral leishmaniasis or kala-azar is a potent parasitic infection causing death
      of thousands of people each year. Medicinal compounds currently available for the
      treatment of kala-azar have serious side effects and decreased efficacy owing to
      the emergence of resistant strains. The type of immune reaction is also to be
      considered in patients infected with Leishmania donovani (L. donovani). For
      complete eradication of this disease, a high level modern research is currently
      being applied both at the molecular level as well as at the field level. The
      computational approaches like remote sensing, geographical information system
      (GIS) and bioinformatics are the key resources for the detection and distribution
      of vectors, patterns, ecological and environmental factors and genomic and
      proteomic analysis. Novel approaches like GIS and bioinformatics have been more
      appropriately utilized in determining the cause of visearal leishmaniasis and in
      designing strategies for preventing the disease from spreading from one region to
      another.

PMID- 23554716
TI  - Iptakalim, a novel ATP-sensitive potassium channel opener, inhibits pulmonary
      arterial smooth muscle cell proliferation by downregulation of PKC-alpha.
AB  - Iptakalim is a new ATP-sensitive potassium (KATP) channel opener, and it inhibits
      the proliferation of pulmonary arterial smooth muscle cells (PASMCs) and
      pulmonary vascular remodeling. However, the underlying mechanism remains unclear.
      In the present study, we found that iptakalim significantly decreased pulmonary
      artery pressure, inhibited pulmonary ariery remodeling and PKC-alpha
      overexpression in chronic hypoxia in a rat pulmonary hypertension model.
      Iptakalim reduced hypoxia-induced expression of PKC-alpha, and abolished the
      effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner
      in vitro. Moreover, these effects were abolished by glibenclamide, a selective
      KATP channel antagonist. These results indicate that iptakalim inhibits PASMC
      proliferation and pulmonary vascular remodeling induced by hypoxia through
      downregulating the expression of PKC-alpha. Iptakalim can serve as a novel
      promising treatment for hypoxic pulmonary hypertension.

PMID- 23554717
TI  - TSP-1 promotes glomerular mesangial cell proliferation and extracellular matrix
      secretion in Thy-1 nephritis rats.
AB  - The proliferation of glomerular mesangial cells (GMC) and secretion of the
      extracellular matrix (ECM) in rat with Thy-1 nephritis (Thy-1N) resembling human
      mesangioproliferative glomerulonephritis have been explored for many years;
      however, the molecular mechanisms of GMC proliferation and ECM production remain
      unclear. Our previous studies have demonstrated that the thrombospondin-1 (TSP-1)
      gene was involved in mediating rat GMC proliferation and ECM synthesis induced by
      sublytic C5b-9 in vitro. In the present study, the roles of the TSP-1 gene in GMC
      proliferation, ECM production, and urinary protein secretion in Thy-1N rats were
      determined by using TSP-1 small hairpin RNA, and the results revealed that
      silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation
      (P < 0.01) and ECM secretion (P < 0.01) as well as urinary protein secretion (P <
      0.05) in Thy-1N rats. Together, the current findings suggested that TSP-1 gene
      expression was required for GMC proliferation and ECM production in Thy-1N rats.

PMID- 23554719
TI  - Fracture resistance of posterior teeth restored with modern restorative
      materials.
AB  - We studied the fracture resistance of maxillary premolars restored with recent
      restorative materials. Fifty maxillary premolars were divided into five groups:
      Group 1 were unprepared teeth; Group 2 were teeth prepared without restoration;
      Group 3 were teeth restored with tetric ceram HB; Group 4 were teeth restored
      with InTen S; and Group 5 were teeth restored with Admira. The samples were
      tested using a universal testing machine. Peak loads at fracture were recorded.
      The teeth restored with Admira had the highest fracture resistance followed by
      those restored with InTen-S and tetric ceram HB. Prepared, unrestored teeth were
      the weakest group. There was a significant difference between the fracture
      resistance of intact teeth and the prepared, unrestored teeth. There was also a
      significant difference among the tested restorative materials. Teeth restored
      with Admira showed no significant difference when compared with the unprepared
      teeth. It was concluded that the teeth restored with Admira exhibited the highest
      fracture resistance.

PMID- 23554718
TI  - Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic
      nephropathy in experimentally induced type 2 diabetes rats.
AB  - Diabetic nephropathy is a major cause of end-stage renal disease (ESRD) in the
      general population. It is estimated that diabetic nephropathy will eventually
      develop in about 40% of all patients with diabetes; therefore, prevention is
      critical for delaying the development and progression of diabetic kidney disease.
      Despite extensive efforts, medical advances are still not successful enough to
      prevent the progression of the disease. In the present study, we focused on the
      comparison of combination therapies and whether they offered additional
      renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally
      administering streptozotocin (90 mg/kg) in neonatal rats and then these rats were
      treated with rosiglitazone (1.0 mg/kg) in combination with glimepiride (0.5
      mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5
      mg/kg). Diabetic nephropathy markers were evaluated by biochemical and ELISA kits
      and renal structural changes were examined by light microscopy and transmission
      electron microscopy. Results show that the combination of pioglitazone with
      glimepiride is more effective in amelioration of diabetic nephropathy than
      rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing
      albumin excretion rate, total protein excretion rate and augmented TNF-a
      signaling during the development of streptozotocin induced type 2 diabetic
      nephropathy.

PMID- 23554720
TI  - Mutational screening of affected cardiac tissues and peripheral blood cells
      identified novel somatic mutations in GATA4 in patients with ventricular septal
      defect.
AB  - The aim of this study was to examine how somatic mutations of the GATA4 gene
      contributed to the genesis of ventricular septal defect (VSD). The coding and
      intron-exon boundary regions of GATA4 were sequenced of DNA samples from
      peripheral blood cells and cardiac tissues of twenty surgically treated probands
      with VSD. Seven novel heterozygous variants were detected in cardiac tissues from
      VSD patients, but they were not detected in the peripheral blood cells of VSD
      patients or in 500 healthy control samples. We replicated 14 single nucleotide
      polymorphisms (SNPs) reported in NCBI. Bioinformatics analysis was performed to
      analyze the possible mechanism by which mutations were linked to VSD. Among those
      variants, c. 1004C>A (p.S335X) occurred in the highly conserved domain of GATA4
      and generated a termination codon, which led to the production of truncated
      GATA4. The seven novel heterozygous GATA4 mutations were only identified in
      cardiac tissues with VSD, suggesting that they are of somatic origin. A higher
      mutation rate in cardiac tissues than in peripheral blood cells implies that the
      genetic contribution to VSD may have been underestimated.

PMID- 23554721
TI  - Evaluation of computed tomography obstruction index in guiding therapeutic
      decisions and monitoring percutanous catheter fragmentation in massive pulmonary
      embolism.
AB  - In the present study, we evaluated computed tomography pulmonary angiography
      (CTPA) in guiding therapeutic decisions and monitoring patients undergoing
      percutaneous catheter fragmentation in acute massive pulmonary embolism. From Jan
      2003 to Dec 2009, 35 patients were diagnosed with acute massive pulmonary
      embolism by CTPA (T0) and treated with percutaneous catheter fragmentation. The
      severity was assessed by CT obstruction index (Qanadli index) and compared with
      Miller index. CTPA, oxygen saturation (SaO2) and pulmonary artery pressure were
      performed as follow-up index. The mean percentage of Qanadli index was (55+/-13)%
      (range, 40%-75%), and Miller index was (62+/-15)% (range, 45%-85%). Correlations
      between them were statistically significant (r = 0.867, P < 0.0001). The Qanadli
      index showed significant reduction [T0: (55+/-13)%; T1: (12+/-10)%; P < 0.001] in
      33 patients. Significant correlation was observed between the Qanadli index, SaO2
      (r = 0.934), and pulmonary artery pressure (r = 0.813). The Qanadli index
      provides an accurate method for distinguishing massive pulmonary embolism from
      sub-massive pulmonary embolism. It can be used to determine therapeutic options
      and monitor clinical outcomes.

PMID- 23554722
TI  - Generation of conditional knockout alleles for PRL-3.
AB  - Phosphatase of regenerating liver-3 (PRL-3) is a member of the protein tyrosine
      phosphatase (PTP) superfamily and is highly expressed in cancer metastases. For
      better understanding of the role of PRL-3 in tumor metastasis, we applied a rapid
      and efficient method for generating PRL-3 floxed mice and investigated its
      phenotypes. A BAC retrieval strategy was applied to construct the PRL-3
      conditional gene-targeting vector. Exon 4 was selected for deletion to generate a
      nonfunctional prematurely terminated short peptide as it will cause a frame-shift
      mutation. Conditional knockout PRL-3 mice were generated by using the Cre-loxP
      system and were validated by Southern blot and RT-PCR analysis. Further analysis
      revealed the phenotype characteristics of PRL-3 knockout mice and wildtype mice.
      In this study, we successfully constructed the PRL-3 conditional knockout mice,
      which will be helpful to clarify the roles of PRL-3 and the mechanisms in tumor
      metastasis.

PMID- 23554723
TI  - Active motif finder - a bio-tool based on mutational structures in DNA sequences.
AB  - Active Motif Finder (AMF) is a novel algorithmic tool, designed based on
      mutations in DNA sequences. Tools available at present for finding motifs are
      based on matching a given motif in the query sequence. AMF describes a new
      algorithm that identifies the occurrences of patterns which possess all kinds of
      mutations like insertion, deletion and mismatch. The algorithm is mainly based on
      the Alignment Score Matrix (ASM) computation by comparing input motif with full
      length sequence. Much of the effort in bioinformatics is directed to identify
      these motifs in the sequences of newly discovered genes. The proposed bio-tool
      serves as an open resource for analysis and useful for studying polymorphisms in
      DNA sequences. AMF can be searched via a user-friendly interface. This tool is
      intended to serve the scientific community working in the areas of chemical and
      structural biology, and is freely available to all users, at
      http://www.sastra.edu/scbt/amf/.

PMID- 23554724
TI  - Implications of oral biofilms in medically at risk persons.
AB  - There is the need to understand the composition of oral biofilms so that
      appropriate preventive and treatment regimens, including using appropriate
      antimicrobials, can be developed further. Additionally, when the systemic effects
      from specific microorganisms in oral biofilms are better understood, more
      targeted preventive treatment options may be recommended for persons at high risk
      for potential systemic diseases such as cardiovascular disease, and for
      aspiration pneumonia. Hence, the possible association between periodontopathic
      microorganisms, and also between cariogenic microorganisms in high caries risk
      persons, and systemic diseases requires further research involving metagenomic
      and large well-designed clinical studies. Effective preventive oral care is
      important for reducing potential systemic diseases.

PMID- 23554725
TI  - Leishmania donovani whole cell antigen delivered with adjuvants protects against
      visceral leishmaniasis in vervet monkeys (Chlorocebus aethiops).
AB  - In a previous immunogenicity and efficacy study in mice, montanide ISA 720 (MISA)
      was indicated to be a better adjuvant than bacillus calmette guerin vaccine (BCG)
      for a Leishmania vaccine. In the present study, we report the safety,
      immunogenicity and efficacy of Leishmania donovani (L. donovani) sonicated
      antigen delivered with alum-BCG (AlBCG), MISA or monophosphoryl lipid A (MPLA) in
      vervet monkeys following intradermal inoculums. Vaccinated and control animals
      were challenged with virulent L. donovani parasites and the parasitic burden was
      determined. Only animals vaccinated with alum-BCG adversely reacted to the
      inoculum by producing ulcerative erythematous skin indurations. Non-parametric
      ANOVA followed by a post test showed significantly higher IgG antibodies, and
      revealed the presence of lymphoproliferative and interferon gamma responses in
      both AlBCG+Ag and MISA+Ag as compared to the MPLA+Ag or other groups (P < 0.001).
      We conclude that L. donovani sonicated antigen containing MISA is safe and is
      associated with protective immune response against Leishmania donovani infection
      in the vervet monkey model.

PMID- 23554726
TI  - Expression, purification and characterization of Mycobacterium tuberculosis RpfE
      protein.
AB  - Resuscitation promoting factor E (RpfE) is one of the five Rpf-like proteins in
      Mycobacterium tuberculosis (M. tuberculosis). These Rpf-like proteins are
      secretory, which make them candidates for recognition by the host immune system.
      In this study, the RpfE gene was amplified from M. tuberculosis, cloned into the
      expression vectors pDE22 and pPRO EXHT, and were expressed in Mycobacterium
      vaccae (M. vaccae) and Escherichia coli DH5alpha, respectively. Both recombinant
      RpfE proteins were purified by Ni-Sepharose affinity chromatography, and were
      given to C57BL/6 mice. The RpfE proteins elicited T cell proliferation, and
      stimulated the production of gamma interferon (IFN-gamma), interleukin-10 (IL-10)
      and IL-12. Our results indicated that the RpfE protein expressed in M. vaccae
      could more efficiently stimulate cellular immune response, making it a promising
      candidate as a subunit vaccine.

PMID- 23554727
TI  - Involvement of adenosine and standardization of aqueous extract of garlic (Allium
      sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic
      preconditioning and myocardial ischemia-reperfusion induced cardiac injury.
AB  - The present study investigated the effect of garlic (Allium sativum Linn.)
      aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced
      cardiac injury, as well as adenosine involvement in ischemic preconditioning and
      garlic extract induced cardioprotection. A model of ischemia-reperfusion injury
      was established using Langendorff apparatus. Aqueous extract of garlic dose was
      standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the
      0.05% dose was found to be the most effective. Higher doses (more than 0.05%)
      were highly toxic, causing arrhythmia and cardiodepression, whereas the lower
      doses were ineffective. Garlic exaggerated the cardioprotective effect of
      ischemic preconditioning. The cardioprotective effect of ischemic preconditioning
      and garlic cardioprotection was significantly attenuated by theophylline (1,000
      umol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct
      size, increased LDH level, and reduced nitrite and adenosine levels. These
      findings suggest that adenosine is involved in the pharmacological and molecular
      mechanism of garlic induced cardioprotection and mediated by the modulation of
      nitric oxide.

PMID- 23554728
TI  - Parthenolide attenuates LPS-induced activation of NF-kappaB in a time-dependent
      manner in rat myocardium.
AB  - Parthenolide (PTN), a selective nuclear factor kappa B (NF-kappaB) inhibitor, has
      been used extensively to inhibit NF-kappaB activation. The duration of the
      inhibitory effect of PTN on NF-kappaB in vivo remains unclear. This study was to
      determine whether a lipopolysaccharide (LPS) challenge 6, 12 and 24 h after the
      administration of PTN could activate NF-kappaB. Rats were devided into five
      groups. The rats in the PTN, PTN+LPS and DMSO groups were injected
      intraperitoneally with PTN or DMSO. After 6, 12 or 24 h, LPS was administered in
      LPS and PTN+LPS groups. The expressions of NF-kappaB p50, IkappaBalpha and p
      IkappaBalpha were inhibited in both PTN and PTN+LPS group at end of 6 and 12 h
      and no effects at 24 h. In summary, myocardial NF-kappaB expression occurs 1 h
      after the administration of LPS. PTN blocks this effect given at 6 h and no
      inhibitory effect 24 h after administration in vivo.

PMID- 23554729
TI  - Soy isoflavone extracts stimulate the growth of nude mouse xenografts bearing
      estrogen-dependent human breast cancer cells (MCF-7).
AB  - We explored the effects of different lifetime exposures to soy isoflavone
      extracts on the growth of estrogen-dependent human breast cancer cells (MCF-7)
      implanted into athymic mice of different ovarian statuses. The athymic mice,
      ovariectomized or not, were implanted with MCF-7 cells. Mice were fed with low,
      moderate and high doses of soy isoflavone extract, at dietary concentrations of
      6.25, 12.5 and 25 g/kg, in different reproductive models, respectively. The
      expression of ki-67 was detected by immunohistochemistry. pS2 expression in
      tumors was analyzed by real-time PCR. Estrogen level in the serum was measured by
      chemiluminescence enzyme immunoassay. Total genistein and daidzein levels in
      serum and urine were determined by liquid chromatography-electrospray tandem mass
      spectrometry (LC-ES/MS/MS). In Group A, on week 4, nude mice were exposed to
      different doses of soy iosflavone extracts. In Group B, the experimental diets
      were given to the nude mice following ovariectomy and tumor implantation. In both
      groups, 6.25 and 12.5 g/kg soy isoflavone extracts stimulated the growth of MCF-7
      xenografts, increased pS2 expression, proliferation and estrogen level in serum.
      In both Group B (postmenopausal mouse model) and Group C (premenopausal mouse
      model), soy isoflavone extracts at doses of 6.25 and 12.5 g/kg showed stimulatory
      effects on the growth of MCF-7 tumors. In conclusion, administration of soy
      isoflavone extracts at doses of 6.25 and 12.5 g/kg during adolescence or later in
      life stimulated tumor growth in both menopausal and postmenopausal mouse models.

PMID- 23554730
TI  - Recombinant adenovirus vector-mediated human MDA-7 gene transfection suppresses
      hepatocellular carcinoma growth in a mouse xenograft model.
AB  - Hepatocellular carcinoma is one of the most common tumors in the world. The
      purpose of the present study was to investigate the inhibitory effects of
      adenoviral transduction of human melanoma differentiation-associated gene-7 (MDA
      7) gene on hepatocellular carcinoma, so as to provide a theoretical basis for
      gene therapy of the disease. The human MDA-7 gene was cloned into replication
      defective adenovirus specific to HepG2 cells using recombinant virus technology.
      RT-PCR and Western blotting assays were used to determine the expression of human
      MDA-7 mRNA and MDA-7 protein in HepG2 cells in vitro. Induction of apoptosis by
      overexpression of the human MDA-7 gene was determined by flow cytometry. In-vivo
      efficacy of adenoviral delivery of the human MDA-7 gene was assessed in nude mice
      bearing HepG2 cell lines in vivo by determining inhibition of tumor growth, VEGF
      and CD34 expression, and microvascular density (MVD). The results showed that
      AdGFP/MDA-7 induced apoptosis of HepG2 cells in vitro and significantly inhibited
      tumor growth in vivo (P < 0.05). The intratumoral MVD decreased significantly in
      the treated tumors (P < 0.05). We conclude the recombination adenovirus AdGFP/MDA
      7 can effectively express biologically active human MDA-7, which leads to
      inhibition of hepatocellular carcinoma growth.

PMID- 23554731
TI  - Zinc-deficient diet aggravates ventilation-induced lung injury in rats.
AB  - We investigated the effects of zinc deficiency on acute lung injury (ALI) induced
      by mechanical ventilation. Male Sprague-Dawley rats were fed with a zinc
      deficient or zinc-proficient diet for 4 weeks, and then received mechanical
      ventilation at normal frequency and pressure for 30 min. Total protein, cell
      count, the number of polymorphonuclear neutrophil (PMN) in the bronchoalveolar
      lavage (BAL), and vascular endothelial growth factor (VEGF) expression in the
      lung were determined. Activation of nuclear factor-kappaB (NF-kappaB) was
      detected by examining the phosphorylation of NF-kappaB (pNF-kappaB p65) and the
      expression of inhibitor of NF-kappaB (pI-kBalpha). Compared to the controls,
      total cell count and the number of PMNs were significantly increased to 160% and
      140%, respectively, in zinc-deficient rats treated with ventilation. Activation
      of NF-kappaB was significantly increased and VEGF was also increased to three
      folds. Zinc deficiency aggravated the inflammatory response in rats and was
      associated with the overexpression of VEGF in response to mechanical ventilation.
      Zinc supplementation may be beneficial to zinc-deficient patients during
      mechanical ventilation.

PMID- 23554732
TI  - Postoperative intussusception in infants and children: a report of seven cases.
AB  - Postoperative intussusception is an uncommon but serious condition in infants and
      children. Here, we report seven cases of postoperative intussusception in infants
      and children who were seen at our institution over the last 13 y. The patients
      showed increased nasogastric drainage, vomiting, lack of stool, and/or growing
      abdominal distension 2 to 9 d following abdominal surgery. Manual reduction was
      successful in five cases. In two cases, necrosis was found and intestinal
      resection and anastomosis were carried out. No recurrence was observed at six
      months of follow-up. Postoperative intussusception should be suspected in
      pediatric surgical patients who showed signs of intestinal obstruction in the
      early postoperative period.

PMID- 23554733
TI  - PET imaging for receptor occupancy: meditations on calculation and
      simplification.
AB  - This invited mini-review briefly summarizes procedures and challenges of
      measuring receptor occupancy with positron emission tomography. Instead of
      describing the detailed analytic procedures of in vivo ligand-receptor imaging,
      the authors provide a pragmatic approach, along with personal perspectives, for
      conducting positron emission tomography imaging for receptor occupancy, and
      systematically elucidate the mathematics of receptor occupancy calculations in
      practical ways that can be understood with elementary algebra. The authors also
      share insights regarding positron emission tomography imaging for receptor
      occupancy to facilitate applications for the development of drugs targeting
      receptors in the central nervous system.

PMID- 23554734
TI  - MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2
      gene in transitional cell carcinoma of the bladder.
AB  - The purpose of this study was to determine the relationship between methylation
      status of the insulin-like growth factor 2 (IGF-2) gene and
      methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in bladder
      transitional cell carcinoma tissues in a Chinese population. The polymorphisms of
      the folate metabolism enzyme gene MTHFR were studied by restrictive fragment
      length polymorphism (RFLP). PCR-based methods of DNA methylation analysis were
      used to detect the CpG island methylation status of the IGF-2 gene. The
      association between the methylation status of the IGF-2 gene and clinical
      characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant
      hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and
      12.4% normal bladder tissues, respectively, while hypomethylation was not
      detected in almost all normal bladder tissues. The hypomethylation rate of the
      IGF-2 gene in cancer tissues was significantly higher in patients with lymph node
      metastasis than in those without lymph node metastasis (46.3% vs 17.2%, P =
      0.018). No association was found between aberrant DNA methylation and selected
      factors including sex, age, tobacco smoking, alcohol consumption and green tea
      consumption. After adjusting for potential confounding variables the variant
      allele of MTHFR C677T was found to be associated with hypomethylation of the IGF
      2 gene. Compared with wildtype CC, the odds ratio was 4.33 (95% CI=1.06-10.59)
      for CT and 4.95 (95% CI=1.18-12.74) for TT. MTHFR 677 CC and CT genotypes might
      be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and
      the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the
      genesis and progression of bladder transitional cell carcinoma.

PMID- 23554735
TI  - Prevalence of intestinal parasitic infections in certified food-handlers working
      in food establishments in the City of Nairobi, Kenya.
AB  - Most intestinal parasites are cosmopolitan with the highest prevalence in the
      tropics and subtopics. Rural-to-urban migration rapidly increases the number of
      food eating places in towns and their environs. Some of these eating
      estabishments have poor sanitation and are overcrowded, facilitating disease
      transmission, especially through food-handling. Our investigations in Nairobi,
      therefore, were set to determine the presence of intestinal parasites in food
      handlers with valid medical certificates. Direct and concentrated stool
      processing techniques were used. Chisquare test and ANOVA were used for data
      analysis. The parasites Ascaris lumbricoides, Entamoeba histolytica and Giardia
      lamblia were observed in certified food-handlers. Significant difference was
      found in parasite frequency by eating classes and gender (chi(2) = 9.49, P =
      0.73), (F = 1.495, P = 0.297), but not in parasite occurrence between age
      brackets (chi(2) = 6.99, P = 0.039). The six-month medical certificate validity
      period may contribute significantly to the presence of intestinal parasites in
      certified food-handlers.

PMID- 23554736
TI  - Cynodon dactylon and Sida acuta extracts impact on the function of the
      cardiovascular system in zebrafish embryos.
AB  - The aim of the present study was to screen cardioactive herbs from Western Ghats
      of India. The heart beat rate (HBR) and blood flow during systole and diastole
      were tested in zebrafish embryos. We found that Cynodon dactylon (C. dactylon)
      induced increases in the HBR in zebrafish embryos with a HBR of (3.968+/-0.344)
      beats/s, which was significantly higher than that caused by betamethosone
      [(3.770+/-0.344) beats/s]. The EC50 value of C. dactylon was 3.738 ug/mL. The
      methanolic extract of Sida acuta (S. acuta) led to decreases in the HBR in
      zebrafish embryos [(1.877+/-0.079) beats/s], which was greater than that caused
      by nebivolol (positive control). The EC50 value of Sida acuta was 1.195 ug/mL.
      The untreated embryos had a HBR of (2.685+/-0.160) beats/s at 3 d post
      fertilization (dpf). The velocities of blood flow during the cardiac cycle were
      (2,291.667+/-72.169) um/s for the control, (4,250+/-125.000) um/s for C. dactylon
      and (1,083.333+/-72.169) um/s for S. acuta. The LC50 values were 32.6 ug/mL for
      C. dactylon and 20.9 ug/mL for S. acuta. In addition, the extracts exhibited no
      chemical genetic effects in the drug dosage range tested. In conclusion, we
      developed an assay that can measure changes in cardiac function in response to
      herbal small molecules and determine the cardiogenic effects by microvideography.

PMID- 23554737
TI  - Quercetin attenuates the progression of monocrotaline-induced pulmonary
      hypertension in rats.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease associated with
      increased constriction and remodeling of the pulmonary vasculature. Quercetin is
      a natural flavonoid and has a variety of pharmacological effects including
      improvement of endothelial cell function. However, its pharmacological effects on
      pulmonary hypertension have been rarely reported. We sought to observe the
      protective effect of quercetin in rats with monocrotaline induced PAH. We divided
      30 male Sprague-Dawley rats randomly into three groups with ten rats in each
      group: the monocrotaline group, the quercetin group and the control group. We
      found that, compared with the controls, the mean pulmonary artery pressure (mPAP)
      and the right ventricular hypertrophy index in the monocrotaline group were
      significantly higher (P < 0.01). Quercetin caused a significant reduction both in
      the mPAP and right ventricular hypertrophy index compared with the monocrotaline
      group (P < 0.01) while no difference was found between the quercetin group and
      the control group (P > 0.05). Monocrotaline induced a marked increase in the wall
      thickness (WT) in small and mid-sized pulmonary arteries compared with the
      controls (P < 0.01). Monocrotaline also induced a marked increase in the wall
      area (WA) in small [(56.38+/-6.65)% in monocrotaline vs. (19.80+/-4.63)% in
      control] and mid-sized [(43.71+/-5.38)% in monocrotaline vs. (14.24+/-3.66)% in
      control] pulmonary arteries (P < 0.01). Quercetin treatment markedly reduced
      monocrotaline induced increase in both WT and WA (P < 0.01), which, however,
      still remained significantly elevated compared with those of the controls (P <
      0.01). Furthermore, compared with controls, proliferating cell nuclear antigen
      (PCNA) expression in the pulmonary artery tissues was markedly increased by
      monocrotaline [(45.59+/-1.27) in monocrotaline vs. (9.64+/-0.69) in controls],
      which was significantly attenuated by quercetin. Our animal experiment indicated
      that quercetin could have protective effects on monocrotaline-induced PAH.

PMID- 23554738
TI  - Resveratrol inhibits angiotensin II-induced ERK1/2 activation by downregulating
      quinone reductase 2 in rat vascular smooth muscle cells.
AB  - Our previous studies showed that resveratrol could inhibit the proliferation of
      vascular smooth muscle cells (VSMCs) and repress mRNA and protein expression of
      quinone reductase 2 (NQO2). This study further explored the potential mechanisms
      whereby resveratrol inhibits the proliferation of rat VSMCs. Lentiviral vectors
      that incorporated NQO2 small interfering RNA (siRNA) were constructed and
      transduced into rat VSMCs. The cell proliferation was detected using the
      bromodeoxyuridine (BrdU) assay. Cultured rat VSMCs were stimulated with
      angiotensin II and the level of reactive oxygen species (ROS) was measured using
      a ROS assay kit. A realtime quantitative PCR was used to detect NQO2 mRNA levels.
      Extracellular signal-regulated kinase (ERK1/2) and NQO2 protein expression were
      determined by Western blotting analysis. The inhibitory effect of resveratrol (10
      and 50 umol/L) on the proliferation of rat VSMCs in the NQO2 siRNA group was
      significantly weaker than that in the normal and scrambled siRNA group (P <
      0.01). The ROS level in the NQO2 siRNA and resveratrol (50 umol/L) treatment
      groups were lower than that in the normal and scrambled siRNA groups (P < 0.01 in
      both). Compared with the normal and scrambled siRNA group, the phosphorylation of
      ERK1/2 was significantly decreased in the NQO2 siRNA and resveratrol (50 umol/L)
      treatment group (P < 0.01 in both). In conclusion, high concentration of
      resveratrol inhibits angiotensin II-induced ERK1/2 phosphorylation and subsequent
      proliferation by down-regulation of NQO2 in cultured rat VSMCs.

PMID- 23554739
TI  - The expression and localization of a novel protein phosphatase inhibitor
      2810408A11Rik in mouse testis and sperm.
AB  - This study investigated the expression and distribution of 2810408A11Rik in mouse
      testis and sperm, and explored its role in spermatogenesis and sperm function.
      The expression levels of 2810408A11Rik mRNA in multiple tissue samples were
      analyzed using bioinformatic resources and RT-PCR technique. A specific rabbit
      polyclonal antibody was prepared by prokaryotic expression of 2810408A11Rik
      recombinant protein and utilized for animal immunization. Western blotting,
      immunohistochemistry and immunofluorescence were used to detect the expression
      and distribution of 2810408A11Rik. The results of the bioinformatic analysis and
      RT-PCR showed that 2810408A11Rik mRNA was specifically expressed in mouse testis,
      and 2810408A11Rik protein included a protein phosphatase inhibitor domain.
      Western blotting assays, immunohistochemistry and immunofluorescence confirmed
      the expression of 2810408A11Rik protein in mouse testis, especially in post
      meiosis round and long spermatids, and that it is localized in the acrosome and
      the post-nucleus area of sperm. Our findings suggest that 2810408A11Rik may play
      an important role in spermatogenesis, sperm capacitation and fertilization.

PMID- 23554741
TI  - Baicalin modulates microRNA expression in UVB irradiated mouse skin.
AB  - This study aimed to evaluate the effects of baicalin on ultraviolet radiation B
      (UVB)-mediated microRNA (miRNA) expression in mouse skin. We determined miRNA
      expression profiles in UVB irradiated mice, baicalin treated irradiated mice, and
      untreated mice, and conducted TargetScan and Gene Ontology analyses to predict
      miRNA targets. Three miRNAs (mmu-miR-125a-5p, mmu-miR-146a, and mmu-miR-141) were
      downregulated and another three (mmu-miR-188-5p, mmu-miR-223 and mmu-miR-22) were
      upregulated in UVB irradiated mice compared with untreated mice. Additionally,
      these miRNAs were predicted to be related to photocarcinogenesis, hypomethylation
      and apoptosis. Three miRNAs (mmu-miR-378, mmu-miR-199a-3p and mmu-miR-181b) were
      downregulated and one (mmu-miR-23a) was upregulated in baicalin treated mice
      compared with UVB irradiated mice, and they were predicted to be related to DNA
      repair signaling pathway. These deregulated miRNAs are potentially involved in
      the pathogenesis of photodamage, and may aid treatment and prevention of UVB
      induced dermatoses.

PMID- 23554740
TI  - Cellular exposure to muscle relaxants and propofol could lead to genomic
      instability in vitro.
AB  - Anesthesia is widely used in several medical settings and accepted as safe.
      However, there is some evidence that anesthetic agents can induce genomic changes
      leading to neural degeneration or apoptosis. Although chromosomal changes have
      not been observed in vivo, this is most likely due to DNA repair mechanisms,
      apoptosis, or cellular senescence. Potential chromosomal alterations after
      exposure to common anesthetic agents may be relevant in patients with genomic
      instability syndromes or with aggressive treatment of malignancies. In this
      study, the P388 murine B cells were cultured in vitro, and spectral karyotyping
      (SKY) was utilized to uncover genome-wide changes. Clinically relevant doses of
      cisatracurium and propofol increased structural and numerical chromosomal
      instability. These results may be relevant in patients with underlying
      chromosomal instability syndromes or concurrently being exposed to
      chemotherapeutic agents. Future studies may include utilization of stimulated
      peripheral blood lymphocytes to further confirm the significance of these
      results.

PMID- 23554742
TI  - UVA1 irradiation inhibits fibroblast proliferation and alleviates pathological
      changes of scleroderma in a mouse model.
AB  - The purpose of the present study was to compare the effects of different doses of
      ultraviolet radiation A1 (UVA1) on human fibroblast proliferation and collagen
      level in a mouse model of scleroderma, so as to identify appropriate irradiation
      doses for clinical treatment of scleroderma. Monolayer from human fibroblasts was
      cultured in vitro, and a mouse model of scleroderma was established by
      subcutaneous injection of 100 uL of 400 ug/mL bleomycin into the back of BALB/c
      mice for 4 weeks. The mouse models and human fibroblasts were divided into UVA1
      exposed (100, 60 and 20 J/cm(2)) and UVA-unexposed groups. At 0, 24 and 48 h
      after exposure, cell proliferation and levels of hydroxyproline and collagen were
      detected. UVA1 irradiation was performed 3 times weekly for 10 weeks, and the
      pathological changes of skin tissues, skin thickness and collagen level were
      observed after phototherapy. Cell proliferation and the levels of hydroxyproline
      and collagen were inhibited after phototherapy, and there was a significant
      difference between the UVA1-exposed cells and UVA1-unexposed cells (P < 0.001).
      In addition, UVA1 phototherapy improved dermal sclerosis and softened the skin,
      and there were significant differences between the high-dose UVA1 group and the
      model group, and the negative group (P < 0.05). It is concluded that UVA1
      radiation can reduce cell proliferation, and decrease hydroxyproline and collagen
      levels in a dose-dependent manner in vitro. High-dose UVA1 phototherapy has
      marked therapeutic effect on scleroderma in the mouse model. Decreased collagen
      level may be related to the reduced number and activity of cells, as well as
      inhibition of collagen synthesis.

PMID- 23554743
TI  - Current perspectives of nanoparticles in medical and dental biomaterials.
AB  - Nanotechnology is gaining tremendous impetus due to its capability of modulating
      metals into their nanosize, which drastically changes the chemical, physical and
      optical properties of metals. Nanoparticles have been introduced as materials
      with good potential to be extensively used in biological and medical
      applications. Nanoparticles are clusters of atoms in the size range of 1-100 nm.
      Inorganic nanoparticles and their nano-composites are applied as good
      antibacterial agents. Due to the outbreak of infectious diseases caused by
      different pathogenic bacteria and the development of antibiotic resistance,
      pharmaceutical companies and researchers are searching for new antibacterial
      agents. The metallic nanoparticles are the most promising as they show good
      antibacterial properties due to their large surface area to volume ratios, which
      draw growing interest from researchers due to increasing microbial resistance
      against metal ions, antibiotics and the development of resistant strains.
      Metallic nanoparticles can be used as effective growth inhibitors in various
      microorganisms and thereby are applicable to diverse medical devices.
      Nanotechnology discloses the use of elemental nanoparticles as active
      antibacterial ingredient for dental materials. In dentistry, both restorative
      materials and oral bacteria are believed to be responsible for restoration
      failure. Secondary caries is found to be the main reason to restoration failure.
      Secondary caries is primarily caused by invasion of plaque bacteria (acid
      producing bacteria) such as Streptococcus mutans and lactobacilli in the presence
      of fermentable carbohydrates. To make long-lasting restorations, antibacterial
      materials should be made. The potential of nanoparticles to control the formation
      of biofilms within the oral cavity is also coming under increasing scrutiny.
      Possible uses of nanoparticles as topically applied agents within dental
      materials and the application of nanoparticles in the control of oral infections
      are also reviewed.

PMID- 23554744
TI  - Admission clinical characteristics and early clinical outcomes among acute
      ischemic stroke patients.
AB  - The purpose of the present study was to investigate the association between
      admission clinical characteristics and outcomes at discharge among acute ischemic
      stroke patients in the Chinese population. A total of 2,673 patients with acute
      ischemic stroke were included in the present study. The clinical characteristics
      at admission and other study variables were collected for all patients. The study
      outcome was defined as neurological deficiency (National Institute of Health
      Stroke Scale score >=10) at discharge or in-hospital death. Compared with the
      subjects without neurological deficiency at discharge or in-hospital death, the
      subjects with neurological deficiency at discharge or in-hospital death had a
      significantly higher prevalence of hyperglycemia or history of atrial
      fibrillation at admission. Age >= 80 years, hyperglycemia, hypertension, and
      history of atrial fibrillation were significantly associated with neurological
      deficiency at discharge or in-hospital death after adjustment for other
      variables. It is concluded that old age (>=80 years), hyperglycemia, hypertension
      and history of atrial fibrillation are significantly associated with neurological
      deficiency at discharge or in-hospital death among patients with acute ischemic
      stroke.

PMID- 23554745
TI  - Weekly intravenous nanoparticle albumin-bound paclitaxel for elderly patients
      with stage IV non-small-cell lung cancer: a series of 20 cases.
AB  - The purpose of this study was to evaluate the efficacy and safety of nanoparticle
      albumin-bound paclitaxel as a rescue regimen in the treatment of patients with
      advanced non-small-cell lung cancer. We retrospectively reviewed the medical
      records of 20 patients with stage IV non-small-cell lung cancer. The patients had
      progressive disease after standard antitumor therapy and subsequently received
      intravenous albumin-bound paclitaxel at the dose of 100 mg/m(2) in weekly
      schedule. Cumulative findings showed that the overall response rate was 30.0%,
      the disease control rate amounted to 40%, and the 1 year survival rate was 30%.
      In addition, the median time to progression and the median survival time reached
      5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions
      and grade 4 adverse effects were reported. In summary, weekly-administered
      albumin-bound paclitaxel seems to be an effective and safe regimen for elderly
      patients with stage IV non-small-cell lung cancer who were refractory to
      conventional therapy.

PMID- 23554746
TI  - Bromocriptine enhances the uptake of (99m)Tc-MIBI in patients with hepatocellular
      carcinoma.
AB  - (99m)Tc-methoxyisobutyl isonitrile (MIBI) is a suitable transport substrate for
      the multidrug resistance gene product P-glycoprotein (P-gp) and widely used for
      tumor imaging. Bromocriptine has been shown to inhibit the ATPase activity and
      the function of P-gp. We hypothesized that bromocriptine could promote the
      accumulation of MIBI by inhibiting P-gp activities, a feature that can be taken
      advantage of for enhancing (99m)Tc-MIBI imaging. In the current study, we sought
      to investigate whether bromocriptine enhanced the uptake of (99m)Tc-MIBI in
      hepatocellular carcinoma patients. Sixty primary hepatocellular carcinoma
      patients received (99m)Tc-MIBI single photon emission computer tomgraphy (SPECT)
      prior to surgery. (99m)Tc-MIBI SPECT was performed 15 and 120 min after injection
      of 20 mCi (99m)Tc-MIBI, and early uptake, delayed uptake (L/Nd), and washout rate
      (L/Nwr) of (99m)Tc-MIBI were obtained. In addition, a second (99m)Tc-MIBI SPECT
      was performed according to the same method 48 h after bromocriptine
      administration. We found that, prior to bromocriptine administration, significant
      MIBI uptake in tumor lesions was noted in only 10 (16.7%, 10/60) patients with
      hepatocellular carcinoma. No significant MIBI uptake was observed in the tumor
      lesions of the remaining 50 (83.3%, 50/60) hepatocellular carcinoma patients.
      Following bromocriptine administration, all the patients without apparent MIBI
      uptake demonstrated significant MIBI uptake on (99m)Tc-MIBI SPECT (P < 0.05). Our
      findings indicate that bromocriptine enhances the uptake of (99m)Tc-MIBI in
      patients with hepatocellular carcinoma.

PMID- 23554747
TI  - Three dimensional structure prediction and proton nuclear magnetic resonance
      analysis of toxic pesticides in human blood plasma.
AB  - The purpose of this study was to investigate the nuclear magnetic resonance (NMR)
      assignments of hydrolyzed products extracted from human blood plasma. The
      correlations between chemical, functional and structural properties of highly
      toxic pesticides were investigated using the PreADME analysis. We observed that
      toxic pesticides possessed higher molecular weight and, more hydrogen bond donors
      and acceptors when compared with less toxic pesticides. The occurrence of
      functional groups and structural properties was analyzed using (1)H-NMR. The (1)H
      NMR spectra of the phosphomethoxy class of pesticides were characterized by
      methyl resonances at 3.7-3.9 ppm (delta) with the coupling constants of 11-16 Hz
      (JP-CH3 ). In phosphoethoxy pesticides, the methyl resonance was about 1.4 ppm
      (delta) with the coupling constant of 10 Hz (JP-CH2 ) and the methylene
      resonances was 4.2-4.4 ppm (delta) with the coupling constant of 0.8 Hz (JP-CH3
      ), respectively. Our study shows that the values of four parameters such as
      chemical shift, coupling constant, integration and relaxation time correlated
      with the concentration of toxic pesticides, and can be used to characterise the
      proton groups in the molecular structures of toxic pesticides.

PMID- 23554748
TI  - Influence of ozone on the rheological and electrical properties of stored human
      blood.
AB  - Blood stored in a blood bank undergoes a series of chemical changes and storage
      lesions. The purpose of this study was to assess the effect of ozone on the
      rheological and electrical properties of stored human blood. Venous blood
      samples, obtained from three healthy humans, were treated with different
      concentrations of ozone (30, 50, 70 and 80 ug/mL) for three weeks in vitro. Ozone
      was generated from portable medical-grade oxygen using electrical corona arc
      discharge. The ultraviolet-visible absorption of hemoglobin in the wavelength of
      300-700 nm showed that ozone in this range did not interact with iron ions and it
      was not toxic below the concentration of 80 ug/mL. The changes of blood viscosity
      were also measured. The electrical conductivity and permittivity, in the
      frequency range from 5 to 50 MHz, were measured in the control and treated
      samples subjected to different concentrations of ozone at different stored
      periods. The results showed that the conductivity and permittivity measurements
      may serve as a useful indicator in the quality assessment of blood samples stored
      in the blood bank.

PMID- 23554749
TI  - Antibacterial activity of calcium hydroxide combined with chitosan solutions and
      the outcomes on the bond strength of RealSeal sealer to radicular dentin.
AB  - The purpose of this study was to investigate the antibacterial activity of
      calcium hydroxide [Ca(OH)2] combined with chitosan solutions against Enterococcus
      faecalis-infected root canal dentin and the effect of this new intracanal
      medicament on the bond strength of RealSeal sealer to radicular dentin. An
      experimental intracanal medicament was prepared by mixing different
      concentrations of chitosan solution (25%, 50%, and 100%, W/V) to Ca(OH)2 powder.
      Antibacterial activity was evaluated and the total numbers of colony forming
      units were determined. Bonding ability of RealSeal sealer to radicular dentin was
      evaluated using push-out bond strength test. Data were analyzed using one-way
      analysis of variance (ANOVA) and Tukey's multiple comparison tests. We found that
      Ca(OH)2 combined with different concentrations of chitosan solutions showed
      better antibacterial activity than Ca(OH)2 mixed with saline, without
      significantly affecting the bond strength of RealSeal sealer to radicular dentin
      (P > 0.05). The findings suggest that Ca(OH)2 combined with chitosan is a
      promising intracanal medicament and may be effective in endodontic therapy.

PMID- 23554750
TI  - Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline
      attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats.
AB  - Diabetic neuropathies are a family of nerve disorders caused by diabetes.
      Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy
      multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and
      thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced
      with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with
      the combination regimen of metformin, pioglitazone and glimipiride or metformin
      and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to
      significantly improved glycemic control, increased grip strength and paw jumping
      response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein
      levels and decreases in urinary protein levels were observed in the animals
      treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined
      treatment of streptozotocin and nicotinamide caused marked degeneration of nerve
      cells, while administration of metformin and sitagliptin showed tissue
      regeneration and no body weight gain. In conclusion, treatment with sitagliptin
      and sitagliptin combined with metformin or amitriptyline results in no body
      weight gain, but causes an increase in grip strength and pain sensitivity,
      exhibits neural protection, and reverses the alteration of biochemical parameters
      in rats with streptozotocin-nicotinamide induced type 2 diabetes.

PMID- 23554751
TI  - Preliminary feasibility and hemodynamic performance of a newly-developed self
      expanding bioprosthesis and 16-F delivery system in transcatheter aortic valve
      implantation in sheep.
AB  - We sought to evaluate the feasibility and hemodynamic performance of a new self
      expanding bioprosthesis and 16-F delivery system in sheep. A 23-mm new self
      expanding aortic bioprosthesis was implanted in sheep (n = 10) with a 16-F
      catheter via the right common carotid artery. Each sheep underwent angiography
      and coronary angiography before intervention, immediately and 1 h after stent
      implantation. Electrocardiographic monitoring was carried out during and 2 h
      after the procedure. Transthoracic echocardiography was employed to detect
      hemodynamic performance before intervention, immediately and 1 and 2 h after
      stent implantation. All sheep were euthanized 2 h after successful implantation
      for macroscopic inspection. In all cases, the new self-expanding aortic
      bioprosthesis was successfully delivered to the aortic root and released with a
      16-F catheter. Successful implantation was achieved in 8 of 10 sheep. Hemodynamic
      performance and device position of successful implantation were stable 2 h after
      device deployment. Atrioventricular block was not observed. We conclude that it
      is feasible to implant the new self-expanding aortic valve with a 16-F delivery
      system into sheep hearts via the retrograde route.

PMID- 23554752
TI  - Telmisartan prevents high-fat diet-induced hypertension and decreases perirenal
      fat in rats.
AB  - We sought to investigate the effects of telmisartan on high-fat diet-induced
      hypertension and to explore the possible underlying mechanisms. Rats receiving
      high-fat diet were randomly divided into two groups, the telmisartan group (n =
      9) and the high-fat diet group (n = 10). The control group consisted of age
      matched rats on a regular diet (n = 10). At the end of the treatment, the body
      weight, blood pressure, insulin sensitivity and serum adiponectin levels of all
      rats were examined, and their visceral fat was extracted and weighed. Our results
      showed that telmisartan improved insulin resistance and dyslipidemia and
      increased serum adiponectin levels. Telmisartan also lowered both systolic blood
      pressure and diastolic blood pressure, and decreased the accumulation of
      perirenal fat associated with high-fat diet. Furthermore, telmisartan increased
      adiponectin mRNA expression in the perirenal fat. Correlation analysis showed
      that both systolic blood pressure and diastolic blood pressure were positively
      correlated with perirenal fat. These effects of telmisartan may be mediated
      through decreases in perirenal fat and contributed to the improvement of
      perirenal fat function. Our findings suggested a strong link between perirenal
      fat and high-fat diet-induced hypertension, and identified telmisartan as a
      potential drug for the treatment of obesity-related hypertension.

PMID- 23554753
TI  - Effects of lysed Enterococcus faecalis FK-23 on experimental allergic rhinitis in
      a murine model.
AB  - In the current study, we sought to investigate whether lysed Enterococcus
      faecalis FK-23 (LFK), a heat-killed probiotic preparation, attenuated eosinophil
      influx into the upper airway and had immunomodulatory activity in a murine
      allergic rhinitis model. Eighteen BALB/c mice were divided into three groups; the
      ovalbumin (OVA)-sensitized/challenged group, which received saline orally for 6
      weeks (OVA group), the OVA-sensitized/challenged group, which received LFK orally
      for 6 weeks (LFK-fed group), and the non-sensitized group, which received saline
      for 6 weeks (saline control group). Nasal rubbing and sneezing were monitored
      during the study. After the final challenge, interleukin (IL)-4, interferon (IFN)
      gamma, and OVA-specific IgE levels in the sera and splenocyte culture
      supernatants were determined, eosinophilic infiltrate into the upper airway was
      quantified, and splenic CD4+CD25+ regulatory T cells (Tregs) were examined by
      flow cytometry. We found that nasal rubbing was significantly reduced in LFK-fed
      mice compared to the OVA group on d 27 and 35, and sneezing was significantly
      inhibited by LFK administration for 35 d. LFK-fed mice had significantly less
      eosinophil influx into the nasal mucosa than the OVA group. There were no
      significant differences between the LFK-fed group and OVA group in the serum and
      splenocyte culture supernatant levels of IL-4, IFN-gamma, and OVA-specific IgE.
      Interestingly, the LFK-fed mice had a significantly greater percentage of splenic
      CD4+CD25+ Tregs than OVA group. Our results indicate that oral administration of
      LFK may alleviate nasal symptoms, reduce nasal eosinophilia, and increase the
      percentage of CD4+CD25+ Tregs in experimental allergic rhinitis.

PMID- 23554754
TI  - Risk factors and long-term health consequences of macrosomia: a prospective study
      in Jiangsu Province, China.
AB  - We sought to determine risk factors associated with fetal macrosomia and to
      explore the long-term consequence of infant macrosomia at the age of 7 years. A
      prospective population based cohort study was designed to examine the
      associations between maternal and perinatal characteristics and the risk of
      macrosomia. A nested case-control study was conducted to explore the long-term
      health consequence of infant macrosomia. The mean maternal age of the macrosomia
      group was 24.74+/-3.32 years, which is slightly older than that in the control
      group (24.35+/-3.14 years, P = 0.000). The mean maternal body mass index (BMI) at
      early pregnancy was 22.75+/-2.81 kg/m(2), which was also higher than that in the
      control group (21.76+/-2.59 kg/m(2), P = 0.000). About 64.6% of macrosomic
      neonates were males, compared with 51.0% in the control group (P = 0.000).
      Compared with women with normal weight (BMI: 18.5-23.9 kg/m(2)), women who were
      overweight (BMI: 24-27.9 kg/m(2)) or obese (BMI>=28 kg/m(2)), respectively, had a
      1.69-fold (P = 0.000) and a 1.49-fold (P = 0.000) increased risks of having a
      neonate with macrosomia, while light weight (BMI<18.5 kg/m(2)) women had an
      approximately 50% reduction of the risk. Furthermore, macrosomia infant had a
      1.52-fold and 1.50-fold risk, respectively, of developing overweight or obesity
      at the age of 7 years (P = 0.001 and P = 0.000). Older maternal age, higher
      maternal BMI at early pregnancy and male gender were independent risk factors of
      macrosomia. Macrosomic infant was associated with an increased predisposition to
      develop overweight or obesity at the beginning of their childhood.

PMID- 23554755
TI  - Reduced turnover times make flexible optical reusable scope with EndoSheath((r))
      Technology significantly cost-effective.
AB  - EndoSheath bronchoscopy (Vision Sciences, Inc.) uses a sterile, disposable
      microbial barrier that may meet the growing needs for safe, efficient, and cost
      effective flexible bronchoscopy. The purpose of this open-label comparative study
      was to compare and calculate the costs-per-airway-procedure of the reusable
      fiberscope when used with and without EndoSheath((r)) Technology; and to record
      the turnover time from the completion of the use of each scope until its
      readiness again for the next use. Seventy-five new patients' airways requiring
      airway maneuvers and manipulations with Vision Sciences, Inc., reusable
      fiberscope with EndoSheath((r)) Technology were evaluated for the costs
      comparisons with reassessed historical costs data for Olympus scope assisted
      tracheal intubations. As compared to costs of an intubation ($158.50) with
      Olympus scope at our institute, the intubation costs with Vision Sciences, Inc.,
      reusable fiberscope with EndoSheath technology was $81.50 (P < 0.001). The mean
      turnover time was 5.44 min with EndoSheath technology as compared to previously
      reported 30 min with Olympus fiberscope (P < 0.001). Based on our institutional
      experience, Vision Sciences, Inc., reusable fiberscope with EndoSheath technology
      is significantly cost effective as compared to the Olympus scope with
      significantly improved turnover times.

PMID- 23554756
TI  - Rehabilitation training improves exercise tolerance after percutaneous coronary
      intervention.
AB  - The aim of this present study was to investigate the effects of training on
      exercise tolerance of patients with coronary heart disease after percutaneous
      coronary intervention. Fifty-seven cases of coronary heart disease after
      percutaneous coronary intervention were divided randomly into the rehabilitation
      training group (26 cases) and control group (31 cases). Patients in the
      rehabilitation training group received rehabilitation training at different
      stages and exercise intensities 3 d after percutaneous coronary intervention for
      3 months. The heart rate, blood pressure, ECG changes in treadmill exercise test,
      and the frequency of anginal episodes were observed. The results showed that NST
      and SigmaST of ECG and the frequency of anginal episodes were significantly
      reduced in the rehabilitation training group. In addition, exercise tolerance was
      improved and the total exercise time was lengthened in these patients. Moreover,
      ST segment depression time and emergence time of angina with exercise were also
      lengthened compared with controls (P < 0.05, or 0.01). However, the heart rate
      and blood pressure before and after exercise of the two groups were similar. The
      study indicated that rehabilitation training could significantly relieve angina,
      amend ischemic features of ECG, and improve exercise tolerance of coronary heart
      disease patients after percutaneous coronary intervention.

PMID- 23554758
TI  - Sequential transcatheter arterial chemoembolization, three-dimensional conformal
      radiotherapy, and high-intensity focused ultrasound treatment for unresectable
      hepatocellular carcinoma patients.
AB  - The purpose of this study was to evaluate the outcome of patients with
      unresectable hepatocellular carcinoma (HCC) treated by sequential therapy of
      transcatheter arterial chemoembolization (TACE), three-dimensional conformal
      radiotherapy (3-DCRT) and high-intensity focused ultrasound (HIFU). From October,
      2005 to September, 2010, 120 patients with unresectable HCC received the
      sequential treatments of several courses of TACE followed in 2-4 weeks by 3-DCRT
      and then a single session of HIFU with a curative intent. The median tumor
      irradiation dose was 40 Gy. Tumor response, toxicity and overall survival rate
      were analyzed. Clinicopathologic factors affecting the primary technique
      effectiveness and overall survival rates were investigated by univariate analysis
      or multivariate analysis. All 120 HCC patients were followed up by the last
      follow-up time. Among these patients, hepatic toxicities due to treatment were
      notable in 9 cases. Gastrointestinal bleeding after the overall treatment
      occurred in 2 cases, leukopenia of grade III was detected in 1 case, radiation
      induced liver disease (RILD) was observed in 2 patients, and first- and second
      degree skin burn around the HIFU treatment zone were observed in 2 patients and 1
      patient, respectively. Among 120 patients, 23, 83 and 14 cases achieved partial
      response, stable disease and progressive disease, respectively. The overall
      survival rates at 1 year, 3 years and 5 years were 70%, 35% and 15%,
      respectively, with a median survival time of 26 months. Both Child-Pugh liver
      function grading and radiation dose were determined to be independent predictors
      for overall survival revealed by the multivariate analysis. It is concluded that
      the sequential therapy of TACE, 3-DCRT and HIFU is a promising therapeutic
      regimen for unresectable HCC.

PMID- 23554757
TI  - Hsa-mir-499 rs3746444 polymorphism and cancer risk: a meta-analysis.
AB  - MicroRNAs (miRNAs) are gene regulators involved in numerous diseases including
      cancer, heart disease, neurological disorders, vascular abnormalities and
      autoimmune conditions. Although hsa-mir-499 rs3746444 polymorphism was shown to
      contribute to the susceptibility of multiple genes to cancer, the data have
      yielded conflicting results. Therefore, this meta-analysis was performed to
      provide a comprehensive assessment of potential association between hsa-mir-499
      rs3746444 polymorphism and cancer risk. In this meta-analysis, a total of 9
      articles regarding 10 eligible case-control studies in English (including 6134
      cases and 7141 controls) were analyzed. No significant association between hsa
      mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated. However,
      an increased risk was observed in the subgroup of breast cancer patients (G
      allele vs A allele: OR = 1.10, 95% CI = 1.00-1.20; P heterogeneity = 0.114; I (2)
      = 53.9%) and population-based studies (G allele vs A allele: OR = 1.12, 95% CI =
      1.00-1.25; P heterogeneity = 0.062; I (2) = 64.0%). The findings suggested an
      association between hsa-mir-499 rs3746444 polymorphism and increased risk to
      breast cancer.

PMID- 23554759
TI  - O-linked N-acetylglucosamine transferase (OGT) is overexpressed and promotes O
      linked protein glycosylation in esophageal squamous cell carcinoma.
AB  - The aim of this present study was to explore the expression and clinical
      significance of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and
      enzymatic O-linked glycosylation (O-GlcNAcation) through the addition of O-linked
      beta-N-acetylglucosamine in esophageal squamous cell carcinoma. OGT expression
      and O-GlcNAcation in 40 samples from patients with esophageal squamous cell
      carcinoma was detected by immunohistochemical staining with anti-OGT antib ody
      and O-GlcNAc-specific antibody RL2, respectively. The relationship between
      pathological and clinical factors of patients was analyzed. We found that the
      expression of OGT was higher in esophageal squamous cell carcinoma samples
      compared to the normal tissues. RL2 antibody level was positively correlated with
      OGT expression, and the metastasis of lymph node, which means the level of O
      GlcNAcation was high and related to the metastasis of lymph node in esophageal
      squamous cell carcinoma. In conclusion, OGT activation is the main reason for
      promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma. O
      GlcNAcylation may play an important role in esophageal squamous cell carcinoma.

PMID- 23554760
TI  - Immunoexpression and prognostic role of p53 in different subtypes of epithelial
      ovarian carcinoma.
AB  - We sought to investigate the significance of p53 expression for epithelial
      ovarian carcinoma. In this study, we used immunohistochemical method to
      investigate the expression patterns of p53 in different subtypes of epithelial
      ovarian carcinoma. We found that the expressions of p53 protein in epithelial
      ovarian cancer (pituita, serosity and intima) were 88.9%, 75% and 100%,
      respectively, while the recurrence rates among three cancer subtypes were
      significantly different (33.3%, 12.5% and 0%, respectively; P < 0.05). Compared
      with patients without lymph node metastasis, the expression of p53 in patients
      with lymph node metastasis was significantly strong (68.75% and 100%,
      respectively; P < 0.05). However, the recurrence rate in the patients with lymph
      node metastasis (40%) was higher than that without lymph node metastasis (6.25%,
      P < 0.05). The expressions of p53 protein in ovarian cancer between I-II (25%)
      stage and II-IV stage (100%) were significantly different (P < 0.05), and the
      recurrence rates between the two groups were significantly different (0% and
      31.25%, respectively, P < 0.05). Therefore, p53 protein has an intimate
      relationship with the malignant degree and the prognosis of ovarian cancer.

PMID- 23554762
TI  - Effect of addition of chitosan to self-etching primer: antibacterial activity and
      push-out bond strength to radicular dentin.
AB  - The purpose of this study was to evaluate the antibacterial activity of a
      modified self-etching primer incorporating chitosan and whether this modification
      affected the bond strength to radicular dentin. A modified self-etching primer
      was prepared by adding chitosan solutions at 0.03%, 0.06%, 0.12% and 0.25% (W/W)
      to RealSeal selfe-tching primer. RealSeal primer without chitosan was used as the
      control. The antibacterial activity of the modified self-etching primer was
      evaluated using the direct contact test against Enterococcus faecalis. The
      bonding ability of the RealSeal system to radicular dentin was evaluated using
      the push-out bond strength test. The modes of failure were examined under a
      stereomicroscope. Data were analyzed using analysis of variance (ANOVA) and
      Tukey's test, with a P-value < 0.05 indicating statistical significance. The
      results showed that the antibacterial properties of the freshly prepared and aged
      modified self-etching primer incorporating chitosan exhibited potent
      antibacterial effect against Enterococcus faecalis compared with the unmodified
      primer. The RealSeal system with the aged modified self-etching primer
      incorporating chitosan showed no significant differences in the bond strength as
      compared with the control (P = 0.99). The findings suggest that modified self
      etching primer incorporating chitosan is a promising antibacterial primer which
      does not adversely affect the bond strength of the RealSeal system to radicular
      dentin.

PMID- 23554761
TI  - Flotillin-2 is an acrosome-related protein involved in mouse spermiogenesis.
AB  - SPERMATOGENESIS IS A COMPLEX PROCESS OF TERMINAL DIFFERENTIATION BY WHICH MATURE
      SPERMS ARE GENERATED, AND IT CAN BE DIVIDED INTO THREE PHASES: mitosis, meiosis
      and spermiogenesis. In a previous study, we established a series of proteomic
      profiles for spermatogenesis to understand the regulation of male fertility and
      infertility. Here, we further investigated the localization and the role of
      flotillin-2 in spermiogenesis. Flotillin-2 expression was investigated in the
      testis of male CD1 mice at various developmental stages of spermatogenesis by
      using Western blotting, immunohistochemistry and immunofluorescence. Flotillin-2
      was knocked down in vivo in three-week-old male mice using intratesticular
      injection of small inhibitory RNA (siRNA), and sperm abnormalities were assessed
      three weeks later. Flotillin-2 was expressed at high levels in male germ cells
      during spermatogenesis. Flotillin-2 immunoreactivity was observed in pachytene
      spermatocytes as a strong dot-shaped signal and in round spermatids as a sickle
      shaped distribution ahead of the acrosome. Immunofluorescence confirmed flotillin
      2 was localized in front of the acrosome in round spermatids, indicating that
      flotillin-2 was localized to the Golgi apparatus. Knockdown of flotillin-2 in
      vivo led to a significant increase in head sperm abnormalities isolated from the
      cauda epididymis, compared with control siRNA-injected testes. This study
      indicates that flotillin-2 is a novel Golgi-related protein involved in sperm
      acrosome biogenesis.

PMID- 23554763
TI  - Secondary metabolite credentials of Evolvulus alsinoides by high performance thin
      layer chromatography (HPTLC).
AB  - Plants and plant-based products are the bases of many modern pharmaceuticals that
      are current in use today for various diseases. The aim of the study was to
      investigate the biochemical constituents and high performance thin layer
      chromatography (HPTLC) finger printing of the ethanolic extract of Evolvulus
      alsinoides. Phytochemical screening was done by standard procedures and HPTLC
      method was also established to analyze alkaloids, flavonoids and phenolic
      compounds from the ethanolic extract of Evolvulus alsinoides. Preliminary
      phytochemical screening showed that ethanol extracted more secondary metabolites
      than other solvents. HPTLC fingerprinting analysis showed the presence of various
      alkaloids, flavonoids and phenols (quercetin) in the ethanolic extract. It can be
      concluded that Evolvulus alsinoides may serve as a source of potent antioxidants
      that may be used in the prevention of various diseases such as cancer, diabetes
      and cardiovascular diseases due to the presence of phenolic compounds. HPTLC
      finger print of Evolvulus alsinoides may be useful in the differentiation of the
      species from adulterants and act as a biochemical marker for this medicinally
      important plant in the pharmaceutical industry and plant systematic studies.

PMID- 23554764
TI  - Gastric cancer presenting with solitary gigantic pelvic metastasis.
AB  - Bone metastasis of gastric cancer is relatively uncommon in clinical practice.
      Moreover, it is all the more unusual for the primary presentation of gastric
      malignancy to be bone metastasis. Here, we describe a male patient who complained
      of pain and edema in his right lower extremity. Further assessment by computed
      tomography and positron emission tomography revealed an abnormally thickened
      gastric cardia and a giant neoplasm in the right pelvis with bone damage.
      Consequently, the finding of adenocarcinoma cells in pelvic and cardia biopsy
      specimens contributed to the diagnosis of pelvic metastasis from gastric cancer.
      This case report illustrates that stomach cancer has the potential, although far
      less than breast, prostate and lung cancers, to metastasize to bone. In addition,
      it highlights the peculiarity of this bone metastasis which is pelvic, solitary
      and huge.

PMID- 23554765
TI  - Growth hormone receptor expression in human primary gastric adenocarcinoma.
AB  - The aim of this study was to determine the expression of growth hormone receptor
      (GHR) in patients with primary gastric adenocarcinoma. We investigated 48
      specimens of primary gastric adenocarcinoma and their corresponding normal
      gastric mucosa. Immunohistochemistry and reverse transcription-polymerase chain
      reaction (RT-PCR) were used to detect the expression of GHR. Immunohistochemical
      analyses revealed that GHR was expressed in human primary gastric adenocarcinoma
      (36/48, 75.0%) and appeared to be upregulated, compared to the normal mucosa
      (28/48, 58.3%, P < 0.001). A significant correlation was found between GHR
      expression and tumor stage (P < 0.001) and tumor differentiation (P < 0.001). The
      average positive rate of ki-67 in GHR-positive tumors was 16.06%, while the
      positive rate in GHR-negative tumors was 6.17% (P < 0.01). The average apoptosis
      index (AI) of GHR-positive tumors was 3.36%, which was significantly lower than
      that (7.33%) of GHR-negative tumors. In addition, 27 of 48 cases of tumors had
      GHR mRNA expression, while only 17 of all 48 cases of normal mucosa did so. Our
      results indicate that the frequency of GHR was significantly higher in primary
      gastric adenocarcinoma than that in normal gastric mucosa. GHR expression was
      significantly correlated with tumor differentiation and tumor grade. This finding
      supported a possible role of growth hormone in primary gastric adenocarcinoma
      pathophysiology.

PMID- 23554766
TI  - A germline variant N375S in MET and gastric cancer susceptibility in a Chinese
      population.
AB  - MET tyrosine kinase and its ligand, hepatocyte growth factor (HGF), play a
      pivotal role in the activties of tumor cells. A germline missense variant in exon
      2 of the MET gene, N375S (rs33917957 A>G), may alter the binding affinity of MET
      for HGF and thus modify the risk of tumorigenesis. In this study, we performed a
      case-control study to assess the association between N375S and gastric cancer
      risk in 1,681 gastric cancer cases and 1,858 cancer-free controls. Logistic
      regression analysis was applied to estimate crude and adjusted odds ratios (ORs)
      and 95% confidence intervals (CIs) for the associations between genotypes and
      gastric cancer risk. We found that MET N375S variant genotypes (NS/SS) were
      associated with a significantly decreased risk of gastric cancer (OR = 0.78, 95%
      CI = 0.63-0.96, P = 0.021) compared with the wildtype homozygote (NN). The
      finding indicates that this germline variant in MET may decrease gastric cancer
      susceptibility in Han Chinese.

PMID- 23554767
TI  - The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial
      carcinoma.
AB  - The purpose of this study was to determine the relationship between
      hypermethylation of DACT1 gene promoter and lower mRNA expression in bladder
      urothelial carcinoma tissue. The methylation status of 29 urothelial carcinoma
      samples and 29 normal tissue samples were examined by methylation-specific
      polymerase chain reaction (MSP). The DACT1 mRNA transcript levels and DACT1
      protein levels in all samples were then evaluated to define the relationship
      between the methylation status of the DACT1 promoter and its expression at the
      transcriptional and translational levels. Decreased expression of DACT1 was
      detected in 89.66% of urothelial carcinomas (26/29; P < 0.005). Promoter
      hypermethylation was found in 58.62% (17/29) urothelial carcinomas and 25% (7/29)
      normal tissues, respectively (P < 0.05). DACT1 expression was lower in tissues
      where the DACT1 gene promoter was hypermethylated than in unmethylated tissues
      (0.25+/-0.17 vs 0.69+/-0.30, P < 0.05). DACT1 gene hypermethylation was closely
      related to tumor size, grade and stage (P < 0.05). Our results indicate that
      silencing and downregulation of DACT1 mRNA may be implicated in carcinogenesis
      and the progression of bladder urothelial carcinoma, and may be a potential
      prognostic factor.

PMID- 23554768
TI  - STAT3 mediates resistance of CD44(+)CD24(-/low) breast cancer stem cells to
      tamoxifen in vitro.
AB  - We sought to determine whether STAT3 mediated tamoxifen resistance of breast
      cancer stem cells in vitro. The capacities for mammosphere formation and STAT3
      expression of CD44(+)CD24(-/low) MCF-7 and MCF-7 were observed. The CD44(+)CD24(
      /low) subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF
      7 and TAM resistant (TAM-R) cells. Cell cycle, apoptosis, STAT3 and phospho-STAT3
      changes were observed after treatment with tamoxifen. Small interference RNA
      mediated knockdown of STAT3 in TAM-R cells was also performed. CD44(+)CD24(-/low)
      MCF-7 showed higher capacities for mammosphere formation and STAT3 expression
      than total MCF-7. The CD44(+)CD24(-/low) subpopulation was also upregulated in
      TAM-R cells with less sensitivity to adriamycin than MCF-7. Cell cycle changes,
      anti-apoptotic effects and STAT3 changes were also found. Meanwhile, the knock
      down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen. It is
      concluded that STAT3 plays an essential role in breast cancer stem cells, which
      correlated with tamoxifen resistance.

PMID- 23554769
TI  - Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells
      derived from gastric cancer.
AB  - Gastric cancer stem-like cells (GCSCs) have been identified to possess the
      ability of self-renewal and tumor initiation. However, the mechanisms involved
      remain largely unknown. Here, we isolated and characterized the GCSCs by side
      population (SP) sorting procedure and cultured sphere cells (SC) from human
      gastric cancer cell lines SGC-7901, BGC-823, MGC-803, HGC-27 and MKN-28. The
      sorting and culture assay revealed that SP cells proliferated in an asymmetric
      division manner. In addition, SP cells exhibited a higher potential of spheroid
      colony formation and greater drug resistance than non-SP cells (NSP). Moreover,
      the SC were found with enhanced capabilities of drug resistance in vitro and
      tumorigenicity in vivo. Sox2 mRNA and protein was highly and significantly
      overexpressed in the SP cells and SC. Importantly, downregulation of Sox2 with
      siRNA obviously reduced spheroid colony formation and doxorubicin efflux, as well
      as increased apoptosis rate in sphere cells in vitro and suppressed
      tumorigenicity in vivo. These results suggest that both SP cells and cultured SC
      enrich with GCSCs and that Sox2 plays a pivotal role in sustaining stem cell
      properties and might be a potential target for gastric cancer therapy.

PMID- 23554770
TI  - Glycine attenuates myocardial ischemia-reperfusion injury by inhibiting
      myocardial apoptosis in rats.
AB  - Glycine is a well-documented cytoprotective agent. However, whether it has a
      protective effect against myocardial ischemia-reperfusion injury in vivo is still
      unknown. By using an open-chest anesthetized rat model, we found that glycine
      reduced the infarct size by 21% in ischemia-reperfusion injury rats compared with
      that in the vehicle-treated MI/R rats. The left ventricular ejection fraction and
      fractional shortening were increased by 19.11% and 30.98%, respectively, in
      glycine-treated rats. The plasma creatine kinase levels in ischemia-reperfusion
      injury rats decreased following glycine treatment. Importantly, administration of
      glycine significantly inhibited apoptosis in post-ischemia-reperfusion
      myocardium, which was accompanied by suppression of phosphorylated p38 mitogen
      activated protein kinase and c-Jun NH2-terminal kinase, as well as the Fas
      ligand. These results suggest that glycine attenuates myocardial ischemia
      reperfusion injury in vivo by inhibiting cardiomyocytes apoptosis.

PMID- 23554771
TI  - X-ray irradiation selectively kills thymocytes of different stages and impairs
      the maturation of donor-derived CD4(+)CD8(+) thymocytes in recipient thymus.
AB  - The aim of the present study was to determine whether the sensitivity of
      thymocytes to X-ray radiation depends on their proliferative states and whether
      radiation impairs the maturation of donor-derived thymocytes in recipient thymus.
      We assigned 8-week-old C57BL/6J mice into three treatment groups: 1) untreated;
      2) X-ray radiation; 3) X-ray radiation plus bone marrow transplantation with
      donor bone marrow cells from transgenic mice expressing enhanced green
      fluorescent protein (GFP) on a universal promoter. After 4 weeks, the size of the
      thymus, the number and proliferation of thymocytes and ratios of different stage
      thymocytes were analyzed by immunohistochemistry and flow cytometry. The results
      showed that: 1) CD4(+)CD8(+) thymocytes were more sensitive to X-ray radiation
      induced cell death than other thymocytes; 2) the proliferative capacity of
      CD4(+)CD8(+) thymocytes was higher than that of other thymocytes; 3) the size of
      the thymus, the number of thymocytes and ratios of thymocytes of different stages
      in irradiated mice recovered to the normal level of untreated mice by bone marrow
      transplantation; 4) the ratio of GFP-positive CD4(+)CD8(+) thymocytes increased
      significantly, whereas the ratio of GFP-positive CD4(+) or CD8(+) thymocytes
      decreased significantly. These results indicate that the degree of sensitivity of
      thymocytes to X-ray radiation depends on their proliferative states and radiation
      impairs the maturation of donor-derived CD4(+)CD8(+) thymocytes in recipient
      thymus.

PMID- 23554772
TI  - Hydrogen-rich saline protects against ultraviolet B radiation injury in rats.
AB  - Exposure of skin to solar ultraviolet (UV) radiation induces photo-damage.
      Ultraviolet B (UVB) is the major component of UV radiation which induces the
      production of reactive oxygen species (ROS) and plays an important role in photo
      damage. Hydrogen gas reduces ROS and alleviates inflammation. In this study, we
      sought to demonstrate that hydrogen-rich saline has the effect on skin injuries
      caused by UVB radiation. UVB radiation was irradiated on female C57BL/6 rats to
      induce skin injury. Hydrogen-rich saline and nitrogen-rich saline were
      administered to rats by intraperitoneal injection. Skin damage was detected by
      microscope after injury. UVB radiation had a significant affection in tumor
      necrosis factor alpha, interleukin (IL)-1beta and IL-6 levels, tissue superoxide
      dismutase, malondialdehyde and nitric oxide activity. Hydrogen-rich saline had a
      protective effect by altering the levels of these markers and relieved
      morphological skin injury. Hydrogen-rich saline protected against UVB radiation
      injury, possibly by reducing inflammation and oxidative stress.

PMID- 23554773
TI  - Corrigendum to "Role of remote sensing, geographic bioinformatics system and
      bioinformatics in kala-azar epidemiology" [originally published as J Biomed Res
      2011, 25(6):373-384; doi:10.1016/S1674-8301(11)60050-X].

PMID- 23554774
TI  - Cyclosporine A stimulated hair growth from mouse vibrissae follicles in an organ
      culture model.
AB  - Hypertrichosis is one of the most common side effects of systemic cyclosporine A
      therapy. It has been previously shown that cyclosporine A induces anagen and
      inhibits catagen development in mice. In the present study, to explore the
      mechanisms of cyclosporine A, we investigated the effects of cyclosporine A on
      hair shaft elongation, hair follicle cell proliferation, apoptosis, and mRNA
      expression of selected growth factors using an organ culture model of mouse
      vibrissae. In this model, cyclosporine A stimulated hair growth of normal mouse
      vibrissae follicles by inhibiting catagen-like development and promoting matrix
      cell proliferation. In addition, cyclosporine A caused an increase in the
      expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor
      (HGF), and nerve growth factor (NGF), and inhibited follistatin expression. Our
      findings provide an explanation for the clinically observed effects of
      cyclosporine A on hair growth. The mouse vibrissae organ culture offers an
      attractive model for identifying factors involved in the modulation of hair
      growth.

PMID- 23554775
TI  - Overexpression of the mTERT gene by adenoviral vectors promotes the proliferation
      of neuronal stem cells in vitro and stimulates neurogenesis in the hippocampus of
      mice.
AB  - We sought to construct the adenoviral vector carrying the gene encoding mouse
      telomerase reverse transcriptase (mTERT), as well as detect its expression and
      effect on the proliferation of neuronal stem cells. mTERT was amplified by RT-PCR
      and then the eukaryotic expression vector of pDC-EGFP-TERT was constructed. After
      DNA sequence analysis, we detected that there were 293 cells transfected with pDC
      EGFP-TERT and helper adenovirus plasmid pBHG lox DeltaE1, and three Cre using
      Lipofectamine 2000 mediation, named Ad-mTERT-GFP, to package adenoviral
      particles. The Ad-mTERT-GFP was used to infect neuronal stem cells and then the
      expression and activity of mTERT were detected. In addition, Bromodeoxyuridine
      labeling test identified the impact of mTERT overexpression on proliferation of
      neuronal stem cells. The recombinant adenoviral vector confirmed that mTERT was
      successfully constructed. Overexpression of mTERT stimulated the proliferation of
      neuronal stem cells both in vitro and in vivo. mTERT overexpression via
      adenoviral vector carrying mTERT cDNA upregulated the ability of proliferation in
      neuronal stem cells.

PMID- 23554776
TI  - MiRNA-429 suppresses the growth of gastric cancer cells in vitro.
AB  - Micro-RNAs (miRNAs) have been found to be implicated in a very wide range of
      physiological processes. This study was aimed to investigate the regulation of
      miRNA-429 (miR-429) in gastric cancer cells on cell proliferation and apoptosis.
      Quantitative PCR was employed to detect the expressions of miR-429 after
      eukaryotic expression plasmid of miR-429 and its inhibitor were transiently
      transfected into poorly differentiated human gastric cancer cell line BGC823. The
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction
      assays were used to examine proliferation ability. Apoptosis was analyzed by flow
      cytometry after transfection. The results showed that 48 h after transfection,
      overexpression of miR-429 reached maximum efficiency. Compared with mock
      transfection, miR-429 inhibited tumor cell proliferation significantly (P < 0.05)
      at 48 h and 72 h. of Overexpression of miR-429 promoted tumor cell apoptosis when
      compared with mock transfected cells (P < 0.05). On the contrary, miR-429
      inhibitor promoted tumor cell proliferation and inhibited apoptosis when compared
      with controls (P < 0.05). Our results suggested that miRNA-429 may serve as a
      tumor suppressor during tumorigenesis of gastric cancer and may be a potential
      gastric cancer therapeutic target.

PMID- 23554777
TI  - Omega-3 fatty acid improves the clinical outcome of hepatectomized patients with
      hepatitis B virus (HBV)-associated hepatocellular carcinoma.
AB  - Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical
      outcome of patients undergoing certain operations; however, its benefits for
      patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma
      (HCC) who have undergone hepatectomy are still not clear. The aim of this study
      was to evaluate the effect of omega-3 fatty acid supplemented total parenteral
      nutrition on the clinical outcome of patients with HBV-associated HCC who
      underwent hepatectomy at our institution. A total of 63 patients with HBV
      associated HCC who underwent hepatectomy were included in this study. These
      patients were randomly assigned to receive standard total parenteral nutrition
      (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral
      nutrition (the omega-3 fatty acid group, n = 32) for at least 5 d. The study
      endpoints were the occurrence of infection-related complications, recovery of
      liver function and length of hospital stay. The results showed that the omega-3
      fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs
      control, 43.8%, P < 0.05), a better liver function after hepatectomy: alanine
      transaminase (omega-3 fatty acid, 48.23+/-18.48 U/L vs control, 73.34+/-40.60
      U/L, P < 0.01), aspartate transaminase (omega-3 fatty acid, 35.77+/-14.56 U/L vs
      control, 50.53+/-24.62 U/L, P < 0.01), total bilirubin (omega-3 fatty acid,
      24.29+/-7.40 mmol/L vs control, 28. 37+/-8.06 mmol/L, P < 0.05) and a shorter
      length of hospital stay (omega-3 fatty acid, 12.71+/-2.58 d vs control, 15.91+/
      3.23 d, P < 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98+/-5.63
      pg/mL vs control, 35.55+/-7.5 pg/mL, P < 0.01) and TNF-alpha (omega-3 fatty acid,
      4.43+/-1.22 pg/mL vs control, 5.96+/-1.58 pg/mL, P < 0.01) after hepatectomy were
      significantly lower in the omega-3 fatty acid group than those of the control
      group. In conclusion, administration of omega-3 fatty acid may reduce infection
      rate and improve liver function recovery in HBV-associated HCC patients after
      hepatectomy. This improvement is associated with suppressed production of
      proinflammatory cytokines in these patients.

PMID- 23554779
TI  - The susceptibility of T5-TG12 of the CFTR gene in chronic bronchitis occurrence
      in a Chinese population in Jiangsu province, China.
AB  - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
      have been implicated in the onset of cystic fibrosis and other clinical
      respiratory disorders. In the present study, we investigated the role of CFTR
      variations, poly-T, TG-repeats, and M470V in susceptibility to bronchial asthma
      and chronic bronchitis in a Chinese population in Jiangsu province, China. A
      total of 72 bronchial asthma patients, 68 chronic bronchitis patients, and 117
      healthy subjects were included in this study. The Tn-TGm haplotype was sequenced
      and the CFTR variant M470V was detected using restriction fragment length
      polymorphism (RFLP). We found that the frequency of T5-TG12-V470 in chronic
      bronchitis patients was 0.07%, which was notably higher than that in healthy
      subjects (0.01%) and bronchial asthma patients (0.04%). Thus, the presence of the
      T5-TG12 haplotype of the CFTR gene is likely to play a role in the development
      and progression of respiratory conditions, such as chronic bronchitis.

PMID- 23554780
TI  - Genetic variants of the class A scavenger receptor gene are associated with
      coronary artery disease in Chinese.
AB  - The class A scavenger receptor, encoded by the macrophage scavenger receptor 1
      (MSR1) gene, is a pattern recognition receptor (PPR) primarily expressed in
      macrophages. It has been reported that genetic polymorphisms of MSR1 are
      significantly associated with the number of diseased vessels and coronary artery
      narrowing greater than 20% in Caucasians. However, whether it links genetically
      to coronary artery disease (CAD) in Chinese is not defined. Here, we performed an
      independent case-control study in a Chinese population consisting of 402 CAD
      cases and 400 controls by genotyping ten single nucleotide polymorphisms (SNPs)
      of MSR1. We found that rs416748 and rs13306541 were significantly associated with
      an increased risk of CAD with per allele odds ratio (OR) of 1.56 [95% confidence
      interval (CI) = 1.28-1.90; P < 0.001] and 1.70 (95% CI = 1.27-2.27; P < 0.001),
      respectively. Our results indicate that genetic variants of MSR1 may serve as
      predictive markers for the risk of CAD in combination with traditional risk
      factors of CAD in Chinese population.

PMID- 23554778
TI  - Apelin and vascular endothelial growth factor are associated with mobilization of
      endothelial progenitor cells after acute myocardial infarction.
AB  - This study was designed to determine the levels of early endothelial progenitor
      cells (EPCs), apelin, vascular endothelial growth factor (VEGF) and stromal cell
      derived growth factor-1 (SDF-1) after acute myocardial infarction (AMI), and to
      investigate the relationships between these cytokines and early EPCs. Early EPCs,
      defined as CD133(+), KDR(+), and CD34(+) cells, were quantified by flow
      cytometry. The levels of early EPCs and those cytokines in AMI patients were
      significantly different from those with coronary artery disease or controls (P <
      0.05). Plasma apelin levels were inversely correlated with Gensini score and
      early EPCs (both P < 0.01). Early EPCs, VEGF and SDF-1 showed different patterns
      of changes in AMI patients during the first 24 h. The trend in the change of
      early EPCs was proportionally correlated with that of VEGF (P < 0.05). AMI
      patients exhibited increased early EPCs with remarkably decreased apelin levels
      and enhanced VEGF levels.

PMID- 23554781
TI  - Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats
      with heart failure induced by adriamycin.
AB  - Our previous studies have shown that the cardiac sympathetic afferent reflex is
      enhanced in rats with chronic heart failure (CHF) induced by coronary artery
      ligation and contributes to the over-excitation of sympathetic activity. We
      sought to determine whether sympathetic activity and cardiac sympathetic afferent
      reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang
      II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic
      activity and cardiac sympathetic afferent reflex. Heart failure was induced by
      intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg).
      Six weeks after the first injection, the rats underwent anesthesia with urethane
      and alpha-chloralose. After vagotomy and baroreceptor denervation, cardiac
      sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and
      mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0
      nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious
      rats was performed to evaluate sympathetic activity. The renal sympathetic nerve
      activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats
      and the maximum depressor response of MAP induced by hexamethonium was
      significantly greater in adriamycin rats than that in control rats. Bilateral PVN
      microinjection of angiotensin II (Ang II) caused larger responses of the cardiac
      sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in
      adriamycin rats than control rats. These results indicated that both sympathetic
      activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the
      PVN was involved in the enhanced sympathetic activity and cardiac sympathetic
      afferent reflex in rats with adriamycin-induced heart failure.

PMID- 23554782
TI  - Overexpression of angiopoietin-1 reduces doxorubicin-induced apoptosis in
      cardiomyocytes.
AB  - Doxorubicin (Dox) is a major anticancer chemotherapeutic agent. However, it
      causes cardiomyopathy due to the side effect of cardiomyocyte apoptosis. We have
      previously reported that angiopoietin-1 significantly reduced myocardial
      infarction after ischemic injury and protected cardiomyocytes from oxidative
      stress-induced apoptosis. It is hypothesized that angiopoietin-1 may protect
      cardiomyocytes from Dox-induced apoptosis. Cardiomyocytes H9C2 were transfected
      with adenovirus expressing angiopoietin-1 (Ad5-Ang-1) 24 h before the cells were
      challenged with Dox at a concentration of 2 umol/L. Ad5-GFP served as the vector
      control. Cardiomyocyte apoptosis was evaluated using Annexin V-FITC staining and
      caspase-3 and caspase-8 activity was determined by Western blotting. The results
      showed that Dox treatment significantly induced cardiomyocyte apoptosis as
      evidenced by the greater number of Annexin V-FITC stained cells and increases in
      caspase-3 and caspase-8 activity. In contrast, overexpression of angiopoietin-1
      significantly prevented Dox-induced cardiomyocyte apoptosis. To elucidate the
      mechanisms by which angiopoietin-1 protected cells from Dox-induced apoptosis, we
      analyzed both extrinsic and intrinsic apoptotic signaling pathways. We observed
      that angiopoietin-1 prevented Dox-induced activation of both extrinsic and
      intrinsic apoptotic signaling pathways. Specifically, angiopoietin-1 prevented
      DOX-induced increases in FasL and Bax levels and cleaved caspase-3 and caspase-8
      levels in H9C2 cells. In addition, overexpression of angiopoietin-1 also
      activated the pro-survival phosphoinositide-3 kinase (PI3K)/Akt signaling pathway
      and decreased Dox-induced nuclear factor-kappaB (NF-kappaB) activation. Our data
      suggest that promoting the expression of angiopoietin-1 could be a potential
      approach for reducing Dox-induced cardiomyocyte cytoxicity.

PMID- 23554784
TI  - Sinomenine reduces iNOS expression via inhibiting the T-bet IFN-gamma pathway in
      experimental autoimmune encephalomyelitis in rats.
AB  - Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant
      Sinomenium acutum. It is widely used as an immunosuppressive drug for treating
      rheumatic and arthritic diseases. In our previous studies, we found that
      sinomenine reduced cellular infiltration within the spinal cord and alleviated
      experimental autoimmune encephalomyelitis (EAE) in rats. In this study, we
      further investigated the mechanisms of sinomenine treatment in EAE rats. In EAE
      rats, treatment with sinomenine exerted an anti-inducible NO synthase (anti-iNOS)
      effect, which is related to the reductions of Th1 cytokine interferon-gamma (IFN
      gamma) and its transcription factor, T-bet, in spinal cords. Moreover, sinomenine
      treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat
      interleukin 12 reduced the expression of T-bet and IFN-gamma in vitro and also
      reduced the capability of supernatants of splenocyte culture to induce iNOS
      expression by primary astrocytes. However, sinomenine had no direct inhibitory
      effect on iNOS produced by astrocytes cultured with IFN-gamma and tumor necrosis
      factor alpha in vitro. In conclusion, the anti-iNOS effect of sinomenine on EAE
      is mediated via the suppression of T-bet /IFN-gamma pathway.

PMID- 23554783
TI  - Memantine combined with environmental enrichment improves spatial memory and
      alleviates Alzheimer's disease-like pathology in senescence-accelerated prone-8
      (SAMP8) mice.
AB  - Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the
      treatment of moderate to severe Alzheimer's disease (AD). Environmental
      enrichment (EE) has shown significant beneficial effects on functional
      improvement in AD. In this study, we sought to determine whether combining these
      two distinct therapies would yield greater benefit than either drug used alone.
      We investigated the effect of memantine combined with EE on spatial learning and
      memory and AD-like pathology in a widely used AD model, the senescence
      accelerated prone mice (SAMP8). The SAMP8 mice were randomly assigned to enriched
      housing (EH) or standard housing (SH), where either memantine (20 mg/kg) or
      saline was given by gastric lavage once daily continuously for eight weeks. Our
      results showed that, when provided separately, memantine and EE significantly
      improved spatial learning and memory by shortening escape latencies and
      increasing the frequency of entrance into the target quadrant. When combined,
      memantine and EE showed additive effect on learning and memory as evidenced by
      significant shorter escape latencies and higher frequency of target entrance than
      either drug alone. Consistent with the behavior results, pathological studies
      showed that both memantine and EE significantly reduced hippocampal CA1
      neurofibrilliary tangles (NFTs) as well as amyloid beta precursor protein (APP)
      levels. Combining both therapies synergistically lessened NFTs and APP expression
      compared to either drug alone in SAMP8 mice, indicating that the combination of
      memantine with EE could offer a novel and efficient therapeutic strategy for the
      treatment of AD.

PMID- 23554785
TI  - Serum IL-10 from systemic lupus erythematosus patients suppresses the
      differentiation and function of monocyte-derived dendritic cells.
AB  - The role played by cytokines, other than interferon (IFN)-alpha, in the
      differentiation and function of dendritic cells (DCs) in systemic lupus
      erythematosus (SLE), remains unclear. Serum interleukin-10 (IL-10) levels are
      generally elevated in SLE patients, which might modulate the differentiation of
      DCs. In this study, DCs were induced from monocytes either by transendothelial
      trafficking or by culture with granulocyte-macrophage colony-stimulating factor
      (GM-CSF) + IL-4 + tumor necrosis factor (TNF)-alpha. Both systems were used to
      investigate the effects of elevated serum IL-10 level on DC differentiation in
      SLE patients. The results showed that monocyte-derived DCs induced by either SLE
      serum or exogenous IL-10 reduced the expression of human leukocyte antigen (HLA)
      DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited
      an impaired capacity to stimulate allogenic T-cell proliferation. These results
      indicate that serum IL-10 may be involved in the pathogenesis of SLE by
      modulating the differentiation and function of DCs.

PMID- 23554786
TI  - Generation and characterization of an anti-GP73 monoclonal antibody for
      immunoblotting and sandwich ELISA.
AB  - Recently, serum Golgi protein 73 (GP73) levels have been found to be elevated in
      patients with hepatocellular carcinoma (HCC), and GP73 has been proposed as a
      novel marker for HCC. However, GP73 levels in patients remain controversial due
      to the specificity of the anti-GP73 antibody-based enzyme linked immunosorbent
      assay (ELISA). Therefore, an anti-GP73 antibody with high specificity was highly
      demanded. In the present study, by hybridoma screening, we generated an anti-GP73
      monoclonal antibody (mAb) designated as 6A2 using recombinant GP73 protein
      produced by prokaryotic expression. The specificity of 6A2 was evaluated by
      Western blotting, immunohistochemistry and immunoprecipitation. The results
      showed that 6A2 recognized GP73 in both native and denatured forms. In addition,
      we have developed a sandwich ELISA using 6A2 and GP73 polyclonal antibody
      generated in New Zealand white rabbits according to standard procedures, and
      measured the serum GP73 level of patients using this assay. Our results showed
      that serum GP73 levels of HCC patients were significantly higher than those of
      healthy controls (P = 0.0036). Furthermore, for the first time, GP73 serum level
      was found to be elevated in patients with breast cancer compared with healthy
      controls (P = 0.0172).

PMID- 23554787
TI  - Favre-Racouchot syndrome associated with eyelid papilloma: a case report.
AB  - A 55-year-old Chinese man presented with an asymptomatic pedunculated elevation
      on his left lower eyelid which had been gradually increasing in size during the
      past three years. The patient was diagnosed with eyelid papilloma by pathological
      examination. Concomitantly, the patient developed open comedones with a bilateral
      linear distribution, along with oblique wrinkle lines in his infraorbital
      regions. These lesions were noninflammatory and remained unchanged for two years.
      To the best of our knowledge, this distribution of open comedones, especially in
      combination with eyelid papilloma, has not been reported previously in Favre
      Racouchot syndrome.

PMID- 23554789
TI  - Maternal risk factors for low birth weight for term births in a developed region
      in China: a hospital-based study of 55,633 pregnancies.
AB  - Low birth weight (LBW) is an important risk factor for neonatal and infant
      mortality and morbidity in adults.. However, no large scale study on the
      prevalence of LBW and related maternal risk factors in China has been published.
      To explore the effects of maternal factors on LBW for term birth in China, we
      conducted a hospital-based retrospective study of 55, 633 Chinese pregnancy cases
      between 2001 and 2008. Maternal sociodemographic data, history of infertility and
      contraceptive use were obtained. Their medical status and diseases during pre
      pregnancy were examined by physical examination at the first antenatal care
      visit. Maternal medical status before childbirth and pregnancy outcomes,
      including body weight, infant gender, multiple pregnancy and congenital
      anomalies, were recorded. Univariate and multivariate logistic regression, and
      linear regression were used to investigate the relationship between maternal
      factors and term LBW. The general incidence of term LBW was 1.70% in the
      developed area of China. After preliminary analysis using the univariate model,
      low primary education, anemia, hypertensive disorders, placental previa,
      oligohydramnios and premature rupture of membrane were predicted as independent
      factors of term LBW in the multivariate model. Furthermore, the decrease in
      annual frquencies of these risk factors were major causes of gradual decline in
      the incidence of LBW (from 2.43% in 2001 to 1.21% in 2008). The study
      demonstrated that among maternal factors, primary education, anemia and
      hypertensive disorders could contribute to LBW for term birth even in the most
      developed area of China.

PMID- 23554788
TI  - Lipoprotein metabolism in nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide,
      covers a spectrum of pathologies characterized by fatty accumulation in
      hepatocytes in early stages, with potential progression to liver inflammation,
      fibrosis, and failure. A close, yet poorly understood link exists between NAFLD
      and dyslipidemia, a constellation of abnormalities in plasma lipoproteins
      including triglyceride-rich very low density lipoproteins. Apolipoproteins are a
      group of primarily liver-derived proteins found in serum lipoproteins; they not
      only play an extracellular role in lipid transport between vital organs through
      circulation, but also play an important intracellular role in hepatic lipoprotein
      assembly and secretion. The liver functions as the central hub for lipoprotein
      metabolism, as it dictates lipoprotein production and to a significant extent
      modulates lipoprotein clearance. Lipoprotein metabolism is an integral component
      of hepatocellular lipid homeostasis and is implicated in the pathogenesis,
      potential diagnosis, and treatment of NAFLD.

PMID- 23554790
TI  - Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal
      ligament tissue of patients with pelvic floor dysfunction.
AB  - Pelvic organ prolapse (POP) is a disabling disorder in women characterized by a
      loss of pelvic floor support, leading to the herniation of the uterus into or
      through the vagina. POP is a complex problem that likely involves multiple
      mechanisms with limited therapies available, and is associated with defects in
      connective tissue including elastic fibers. This study was designed to
      investigate the expression of fibulin-5 and lysyl oxidase-like 1 (LOXL1) in the
      cardinal ligament in samples taken from the POP group compared to the non-POP
      group. Specimens were obtained during abdominal hysterectomy from the cardinal
      ligament of 53 women with POP and 25 age- and parity- matched women with non-POP
      among post-menopausal women with benign gynecologic pathology. Protein expression
      was evaluated using the immunohistochemical staining method. For statistical
      analyses, chi-square test and Spearman's correlation were used with the
      statistical package SPSS13.0 system. Our results showed that both fibulin-5 and
      LOXL1 expressions were decreased in the cardinal ligament in the POP group
      compared to the non-POP group (P < 0.05). The expression of fibulin-5 and LOXL1
      were correlated closely with the stage of POP, accompanied by stress urinary
      incontinence and frequency of vaginal delivery (P < 0.05), but had no
      relationship with post-menopausal state (P > 0.05). The expression of fibulin-5
      was positively associated with LOXL1 in POP (P < 0.05). We conclude that changes
      in fibulin-5 and LOXL1 expression may play a role in the development of POP.

PMID- 23554791
TI  - Ginkgo biloba leaf extract improves the cognitive abilities of rats with D
      galactose induced dementia.
AB  - Standardized Ginkgo biloba leaf extract has been used in clinical trials for its
      beneficial effects on brain functions, particularly in dementia. Substantial
      experimental evidences indicated that Ginkgo biloba leaf extract (EGB) protected
      neuronal cells from a variety of insults. We investigated the effect of EGB on
      cognitive ability and protein kinase B (PKB) activity in hippocampal neuronal
      cells of dementia model rats. Rats received an intraperitoneal injection of D
      galactose to induce dementia. Forty-eight Spraque-Dawley rats were randomly
      divided into six groups, including the control group, D-galactose group (Gal),
      low-dose EGB group (EGB-L), mid-dose EGB group (EGB-M), high-dose EGB group (EGB
      H) and treatment group. The EGB-L, EGB-M and EGB-H groups were administered with
      EGB and D-galactose simultaneously. Y-maze, cresyl violet staining, TUNEL assays
      and immunohistochemistry staining were performed to detect learning and memory
      abilities, morphological changes in the hippocampus, neuronal apoptosis and the
      expressing level of phospho-PKB, respectively. Rats in the Gal group showed
      decreased abilities of learning and memory, and hippocampal pyramidal cell layer
      was damaged, while EGB administration improved learning and memory abilities. The
      Gal group exhibited many stained, condensed nuclei and micronuclei, either
      isolated or within the cytoplasm of cells (39.5+/-1.4). Apoptotic cells decreased
      in the groups of EGB-L (35.9+/-0.9), EGB-M (16.8+/-1.0) and EGB-H (10.1+/-0.8),
      and there were statistical significances compared with the Gal group.
      Immunoreactivity of phospho-PKB was localized diffusely throughout the cytosol of
      cells in all groups, while the immunoreactivity of the Gal group was weak. EGB
      significantly attenuated learning and memory impairment in a dose-dependent
      manner, while it could decrease the nmber of TUNEL-positive cells, and increase
      the activity of PKB. Our results demonstrated that EGB attenuated memory
      impairment and cell apoptosis in galactose-induced dementia model rats by
      activating PKB.

PMID- 23554792
TI  - Anxiolytic property of hydro-alcohol extract of Lactuca sativa and its effect on
      behavioral activities of mice.
AB  - Lactuca sativa, belonging to the Asteraceae family, is a leafy vegetable known
      for its medicinal properties. This study aimed to understand the mechanism of
      Lactuca sativa extract with respect to pharmacological action.We investigated the
      anxiolytic effects of hydro-alcoholic extract of leaves of Lactuca sativa on
      mice. The behavioral tests performed on mice models to assess anti-anxiety
      properties were: open field test (OFT), elevated plus maze test (EPM), elevated T
      maze test, and marble burying test. Increased locomotor activity and time spent
      in the "open-arm" were observed in extract fed group. Malondialdehyde (MDA) and
      nitrite levels were decreased, catalase and glutathione levels were increased in
      Lactuca sativa treated mice. The data obtained in the present study suggests that
      the extract of Lactuca sativa can afford significant protection against
      anxiolytic activity.

PMID- 23554793
TI  - Medroxyprogestogen enhances apoptosis of SKOV-3 cells via inhibition of the
      PI3K/Akt signaling pathway.
AB  - We sought to assess the effect of progestin on the apoptosis of epithelial
      ovarian cancer cell line SKOV-3 and via regulation of phosphorylation signaling
      in. Epithelial ovarian cancer cell line SKOV-3 was treated with
      medroxyprogestogen, phosphatidylinositol 3-kinase inhibitor LY294002 and vehicle
      control. Akt, phospho-Akt, Bcl-2 and phospho-Bad proteins were examined by
      immunoblotting assays. Medroxyprogestogen-induced apoptosis was assessed by MTT
      assays and Annexin V apoptosis assay. We found no significant difference in Akt
      and Bad expression in both the medroxyprogestogen groups and the control group.
      The levels of phospho-Akt, Bcl-2 and phospho-Bad were decreased in all the
      medroxyprogestogen groups and significantly decreased in the high dose mitogen
      activated protein (MAP) group (10 umol/L). Viability of SKOV-3 was reduced and
      apparent apoptosis of SKOV-3 cells was observed with increased doses of MAP. The
      findings suggest that medroxyprogestogen can induce SKOV-3 cell apoptosis by
      inhibiting Akt phosphorylation.

PMID- 23554794
TI  - All-trans retinoic acid upregulates VEGF expression in glioma cells in vitro.
AB  - All-trans retinoid acid (ATRA) is one of the most potent and most thoroughly
      studied differentiation inducers that induce the differentiation and apoptosis of
      glioma cells. However, the effect of ATRA on angiogenesis of glioma remains
      poorly understood. We examined the effect of ATRA on the expression of vascular
      endothelial growth factor (VEGF) in different glioma cell lines and investigated
      the underlying mechanism, intending to partially reveal the effects of ATRA on
      angiogenesis of glioma. Glioma cells were treated by ATRA at 5 and 10 umol/L. The
      VEGF mRNA transcript levels were determined by real-time RT-PCR and the protein
      levels of VEGF in glioma cells were evaluated by Western blotting assays.
      Moreover, hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA expression was
      analyzed by using real-time RT-PCR. After treatment with 5 and 10 umol/L ATRA,
      the VEGF mRNA transcript levels in glioma cells increased remarkably, compared
      with that in the control group, and the relative protein expression of VEGF was
      also up-regulated. Meanwhile, the HIF-1alpha mRNA expression also increased. ATRA
      increases the expression of VEGF in glioma cells at both transcriptional and
      translational levels.

PMID- 23554795
TI  - Asymptomatic seminal infection of herpes simplex virus: impact on male
      infertility.
AB  - In more than half of infertile men, the cause of their infertility is unknown.
      Several studies revealed the role of viral infections in male infertility. The
      aim of the present study was to determine the prevalence of herpes simplex virus
      1 (HSV-1) and HSV-2 in semen from asymptomatic infertile male patients, and its
      association with altered semen parameters. A total of 70 semen samples were
      collected from infertile men who attended the Research and Clinical Center for
      Infertility in Yazd, Iran. Semen analysis and diagnostic real-time PCR using
      specific primers and probes for HSV-1 and HSV-2 DNA were performed. Comparison of
      semen parameters between virally infected and non-infected samples were performed
      with independent t-test and Mann-Whitney test. Semen analysis showed that
      infertile men fell into two groups, the male factor group and the unexplained
      group. HSV-1 and HSV-2 DNA was detected in 16 (22.9%) and 10 (14.3%) of 70 semen
      samples, respectively. All HSV-positive samples had abnormal semen parameters
      (the male factor group). Although HSV infection was not associated with sperm
      motility and morphological defects, it was correlated with lower sperm count in
      the seminal fluid. The findings suggest that asymptomatic seminal infection of
      HSV plays an important role in male infertility by adversely affecting sperm
      count.

PMID- 23554796
TI  - Surgical approaches for stage I and II thymoma-associated myasthenia gravis:
      feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy in
      comparison with trans-sternal resection.
AB  - Complete resection could be achieved in virtually all myasthenic patients with
      Masaoka stage I and II thymoma using the trans-sternal technique. Whether this is
      appropriate for minimally invasive approach is not yet clear. We evaluated the
      feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy
      for the treatment of Masaoka stage I and II thymoma-associated myasthenia gravis,
      compared to conventional trans-sternal thymectomy. We summarized 33 patients with
      Masaoka stage I and II thymoma-associated myasthenia gravis between April 2006
      and September 2011. Of these, 15 patients underwent right-sided complete VATS
      (the VATS group) by using adjuvant pneuomomediastinum, comparing with 18 patients
      using the trans-sternal approach (the T3b group). No intraoperative death was
      found and no VATS case required conversion to median sternotomy. Significant
      differences between the two groups regarding duration of surgery and volume of
      intraoperative blood loss (P = 0.001 and P < 0.001, respectively) were observed.
      Postoperative morbidities were 26.7% and 33.3% for the VATS and T3b groups,
      respectively. All 33 patients were followed up for 12 to 61 months in the study.
      The cumulative probabilities of reaching complete stable remission and effective
      rate were 26.7% (4/15) and 93.3% (14/15) in the VATS group, which had a
      significantly higher complete stable remission and effective rate than those in
      the T3b group (P = 0.026 and P = 0.000, respectively). We conclude that VATS
      thymectomy utilizing adjuvant pneuomomediastinum for the treatment of stage I and
      II thymoma-associated myasthenia gravis is technically feasible but deserves
      further investigation in a large series with long-term follow-up.

PMID- 23554797
TI  - Tinea faciei in a newborn due to Trichophyton tonsurans.
AB  - We report here the first case of neonatal tinea faciei caused by Trichophyton
      tonsurans in mainland China. The mother of the infant had tinea corpris and tinea
      capitis while the father had tinea incongnito. The infections in the parents were
      mycologically confirmed to be due to Trichophyton tonsurans. Ttinea faciei in the
      infant was cured after two-week topical use of amorolfine cream. The mother
      ceased breastfeeding and took oral terbinafine for 4 weeks. No recurrence was
      observed in the infant during 12 months of follow-up.

PMID- 23554798
TI  - Simulation-a new educational paradigm?
AB  - Simulation is a modern educational tool that has recently gained in the field of
      medical education. The use of simulation continues to expand, and studies
      evaluating the effectiveness of simulation-based medical education are ongoing.
      The history of medical education and adult educational theory are reviewed, and
      the details of effective simulation techniques are described. Finally, outcomes
      of simulation-based medical education are summarized.

PMID- 23554799
TI  - Medical simulation-based education improves medicos' clinical skills.
AB  - Clinical skill is an essential part of clinical medicine and plays quite an
      important role in bridging medicos and physicians. Due to the realities in China,
      traditional medical education is facing many challenges. There are few
      opportunities for students to practice their clinical skills and their
      dexterities are generally at a low level. Medical simulation-based education is a
      new teaching modality and helps to improve medicos' clinical skills to a large
      degree. Medical simulation-based education has many significant advantages and
      will be further developed and applied.

PMID- 23554800
TI  - Development of Leishmania vaccines: predicting the future from past and present
      experience.
AB  - Leishmaniasis is a disease that ranges in severity from skin lesions to serious
      disfigurement and fatal systemic infection. Resistance to infection is associated
      with a T-helper-1 immune response that activates macrophages to kill the
      intracellular parasite in a nitric oxide-dependent manner. Conversely, disease
      progression is generally associated with a T-helper-2 response that activates
      humoral immunity. Current control is based on chemotherapeutic treatments which
      are expensive, toxic and associated with high relapse and resistance rates.
      Vaccination remains the best hope for control of all forms of the disease, and
      the development of a safe, effective and affordable antileishmanial vaccine is a
      critical global public-health priority. Extensive evidence from studies in animal
      models indicates that solid protection can be achieved by immunization with
      defined subunit vaccines or live-attenuated strains of Leishmania. However, to
      date, no vaccine is available despite substantial efforts by many laboratories.
      Major impediments in Leishmania vaccine development include: lack of adequate
      funding from national and international agencies, problems related to the
      translation of data from animal models to human disease, and the transition from
      the laboratory to the field. Furthermore, a thorough understanding of protective
      immune responses and generation and maintenance of the immunological memory, an
      important but least-studied aspect of antiparasitic vaccine development, during
      Leishmania infection is needed. This review focuses on the progress of the search
      for an effective vaccine against human and canine leishmaniasis.

PMID- 23554801
TI  - Prevalence and trends of aminoglycoside resistance in Shigella worldwide, 1999
      2010.
AB  - Shigellosis causes diarrheal disease in humans in both developed and developing
      countries, and multi-drug resistance in Shigella is an emerging problem.
      Understanding changing resistance patterns is important in determining
      appropriate antibiotic treatments. This meta-analysis systematically evaluated
      aminoglycoside resistance in Shigella. A systematic review was constructed based
      on MEDLINE and EMBASE databases. Random-effect models or fixed-effect models were
      used based on P value considering the possibility of heterogeneity between
      studies for meta-analysis. Data manipulation and statistical analyses were
      performed using software STATA 11.0. By means of meta-analysis, we found a lower
      resistance to three kinds of aminoglycosides in the Europe-America areas during
      the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance
      was observed to be the most common drug resistance among Shigella isolates with a
      prevalence of 6.88% (95%CI: 6.36%-7.43%). Comparison of data from Europe-America
      and Asia-Africa areas revealed that Shigella flexneri resistance was greater than
      the resistance calculated for Shigella sonnei. Importantly, Shigella sonnei has
      played a significant role in aminoglycoside-resistance in recent years.
      Similarly, data showed that resistance to these drugs in children was higher than
      the corresponding data of adults. In conclusion, aminoglycoside-resistant
      Shigella is not an unusual phenomenon worldwide. Distribution in Shigella
      resistance differs sharply based on geographic areas, periods of time and
      subtypes. The results from the present study highlight the need for continuous
      surveillance of resistance and control of antibiotic usage.

PMID- 23554802
TI  - Lactobacillus isolates from healthy volunteers exert immunomodulatory effects on
      activated peripheral blood mononuclear cells.
AB  - As probiotics in the gut, Lactobacilli are believed to play important roles in
      the development and maintenance of both the mucosal and systemic immune system of
      the host. This study was aimed to investigate the immuno-modulatory function of
      candiate lactobacilli on T cells. Lactobacilli were isolated from healthy human
      feces and the microbiological characteristics were identified by API 50 CHL and
      randomly amplified polymorphic DNA (RAPD) assays. Anti-CD3 antibody activated
      peripheral blood mononuclear cells (PBMCs) were treated by viable, heat-killed
      lactobacilli and genomic DNA of lactobacilli, and cytokine profiles were tested
      by ELISA. Isolated lactobacilli C44 and C48 were identified as L. acidophilus and
      L. paracacei, which have properties of acid and bile tolerance and inhibitor
      effects on pathogens. Viable and heat-killed C44 and C48 induced low levels of
      proinflammatory cytokines (TNF-alpha, IL-6 and IL-8) and high levels of IFN-gamma
      and IL-12p70 in PBMCs. In anti-CD3 antibody activated PBMCs, viable and heat
      killed C44 increased Th2 cytokine levels (IL-5, IL-6 and IL-10), and
      simultaneously enhanced Th1 responses by inducing IFN-gamma and IL-12p70
      production. Different from that of lactabacillus strains, their genomic DNA
      induced low levels of IL-12p70, IFN-gamma and proinflammatory cytokines in PBMCs
      with or without anti-CD3 antibody activation. These results provided in vitro
      evidence that the genomic DNA of strains of C44 and C48, especially C44, induced
      weaker inflammation, and may be potentially applied for treating allergic
      diseases.

PMID- 23554803
TI  - Etiological risk factors for subfertility among Palestinian women in Gaza.
AB  - The inability to procreate is frequently considered a personal tragedy and a
      hardship for couples, impacting on the entire family and even the local
      community. In Gaza strip, Palestine, there has been no study on etiological risk
      factors for subfertility. The present study aimed to identify risk factors
      associated with subfertility among women in Gaza, Palestine. One hundred and
      sixty-nine women in the study group and 115 women in the control group were
      included. Cases were selected randomly from those referred to the Al Basma
      Fertility Center, Gaza, Palestine. Data were collected through close-ended
      questionnaire, sonography, hormonal analysis and thrombophilia profile that
      included the methylenetetrahydrofolate reductase (MTHFR 677 C > T), factor V
      leiden (1691 G > A) and prothrombin (20210 G > A) genes. By using univariate
      analyses, the effects of different patient-related variables on the presence of
      subfertility were evaluated. A multiple logistic regression model was
      constructed, crude and adjusted odds ratios (OR) and 95% confidence intervals
      (95% CI) were calculated. The findings showed that 73.5 % (169/230) of the women
      referred to the Al Basma Center sought treatment for subfertility. Different
      etiological risk factors were associated with subfertility, the most frequent of
      which in descending order were: thrombophilic disorders, fallopian tube problems,
      sex hormone abnormalities and polycystic ovary syndrome with an adjusted OR of
      21.42, 13.63, 11.69 and 10.29, respectively. In conclusion, several etiological
      risk factors are responsible for subfertility among women in Gaza. Comprehensive
      evaluation of infertile women should be considered in the course of treatment;
      otherwise, the duration of sterility may be extended.

PMID- 23554804
TI  - Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone
      production and promoting germ cell apoptosis in adult rats.
AB  - Bisphenol A (BPA), an estrogenic chemical, has been shown to reduce sperm count;
      however, the underlying mechanisms remain unknown. Herein, we show that oral
      administration of BPA (2 ug/kg) for consecutive 14 days in adult rats (BPA rats)
      significantly reduced the sperm count and the number of germ cells compared to
      controls. The serum levels of testosterone and follicle-stimulating hormone
      (FSH), as well as the level of GnRH mRNA in BPA rats were lower than those of
      control rats. Testosterone treatment could partially rescue the reduction of germ
      cells in BPA rats. Notably, the number of apoptotic germ cells was significantly
      increased in BPA rats, which was insensitive to testosterone. Furthermore, the
      levels of Fas, FasL and caspase-3 mRNA in the testicle of BPA rats were increased
      in comparison with controls. These results indicate that exposure to a low dose
      of BPA impairs spermatogenesis through decreasing reproductive hormones and
      activating the Fas/FasL signaling pathway.

PMID- 23554805
TI  - Integrated DNA-based/biochemical screening for early diagnosis of multiple
      endocrine neoplasia type 2A (MEN2A).
AB  - Multiple endocrine neoplasia type 2A (MEN2A), a subtype of MEN2, is characterized
      by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. A
      Han Chinese pedigree with MEN2A was investigated following confirmation of the
      proband's diagnosis by pathological findings and DNA/biochemical screening. DNA
      samples from 4 other family members were collected and exon 5, 8, 10, 11, 13, 16
      and 18 of the RET proto-oncogene were sequenced and then analyzed. A missense
      mutation of TGG (Trp) to TGC (Cys) at codon 634 (the classic MEN2A mutation) in
      exon 11 of the RET gene was detected in 3 family members, including the proband.
      Sequencing data were compared with the human gene mutation database. Elevated
      serum calcitonin level was detected initially; medullary thyroid carcinoma was
      revealed in the 3 cases and adrenal pheochromocytoma was also found in the
      proband. Elective operations were successfully performed on the adrenal and
      thyroid glands because of pheochromocytoma and medullary thyroid carcinoma. Our
      case study confirms that integrated DNA-based/biochemical screening is crucial
      for early diagnosis of MEN2A and is helpful in the screening of their relatives.
      In addition, DNA-based screening may occasionally uncover a previously unknown
      RET sequence.

PMID- 23554806
TI  - Immediate and delayed micro-tensile bond strength of different luting resin
      cements to different regional dentin.
AB  - We sought to evaluate immediate and delayed micro-tensile bond strength of
      Panavia F2.0 and Multilink Sprint resin cement to superficial, deep and cervical
      dentin. Thirty-six freshly extracted non-carious human molars were sectioned in
      the mesiodistal direction to expose three different dentin regions including
      superficial dentin (1 mm below the dentine-enamel junction), deep dentin (1 mm
      above the highest pulp horn) and cervical dentin (0.5 mm above the cemento-enamel
      junction and 0.5 mm below the dentine-enamel junction). Resin cements were
      applied on dentin surfaces and composite blocks were luted under constant seating
      pressure. Each group was divided into three subgroups according to time
      intervals. Specimens were sectioned to obtain sticks of 1 mm(2) in diameter and
      subjected to microtensile bond strength testing at a cross head speed of 1
      mm/min. Both resin cements showed higher micro-tensile bond strength to
      superficial dentin than that to deep or cervical dentin (P < 0.001). Micro
      tensile bond strengths of Panavia F2.0 were higher than those of Multilink Sprint
      at different dentin regions (P < 0.001). Immediate micro-tensile bond strengths
      were higher than those of delayed micro-tensile bond strengths for both resin
      cements (P < 0.001). It was concluded that resin cements with different chemical
      formulations and applications yield significantly different micro-tensile bond
      strengths to different dentin regions.

PMID- 23554807
TI  - Late anastomotic perforation following surgery for gastric neuroendocrine tumor
      complicated by perforated duodenal ulcer: a case report.
AB  - Neuroendocrine tumors (NETs) are a group of neoplasms that are characterized by
      the secretion of a variety of hormones and diverse clinical syndromes. NETs are
      considered to be rare, but the incidence of NETs has increased rapidly in recent
      years. NETs provide a clinical challenge for physicians because they comprise a
      heterogeneous group of malignancies with a wide range of morphological,
      functional, and behavioral characteristics. Subtotal gastrectomy with Billroth II
      reconstruction is the mainstay of therapy in the management of gastric NETs
      complicated by perforated duodenal ulcer. Late perforation of anastomotic stoma
      as a long-term complication has been rarely reported. Here, we report a case of
      anastomotic perforation 5 years after subtotal gastrectomy due to perforated
      duodenal ulcer and gastric NETs.

PMID- 23554808
TI  - Optimal short-time acquisition schemes in high angular resolution diffusion
      weighted imaging.
AB  - This work investigates the possibilities of applying high-angular-resolution
      diffusion-imaging- (HARDI-) based methods in a clinical setting by investigating
      the performance of non-Gaussian diffusion probability density function (PDF)
      estimation for a range of b-values and diffusion gradient direction tables. It
      does so at realistic SNR levels achievable in limited time on a high-performance
      3T system for the whole human brain in vivo. We use both computational
      simulations and in vivo brain scans to quantify the angular resolution of two
      selected reconstruction methods: Q-ball imaging and the diffusion orientation
      transform. We propose a new analytical solution to the ODF derived from the DOT.
      Both techniques are analytical decomposition approaches that require identical
      acquisition and modest postprocessing times and, given the proposed modifications
      of the DOT, can be analyzed in a similar fashion. We find that an optimal HARDI
      protocol given a stringent time constraint (<10 min) combines a moderate b-value
      (around 2000 s/mm(2)) with a relatively low number of acquired directions (>48).
      Our findings generalize to other methods and additional improvements in MR
      acquisition techniques.

PMID- 23554809
TI  - Synergism between cAMP and PPARgamma Signalling in the Initiation of UCP1 Gene
      Expression in HIB1B Brown Adipocytes.
AB  - Expression of the brown adipocyte-specific gene, uncoupling protein 1 (UCP1), is
      increased by both PPARgamma stimulation and cAMP activation through their ability
      to stimulate the expression of the PPAR coactivator PGC1alpha. In HIB1B brown
      preadipocytes, combination of the PPARgamma agonist, rosiglitazone, and the cAMP
      stimulator forskolin synergistically increased UCP1 mRNA expression, but
      PGC1alpha expression was only increased additively by the two drugs. The
      PPARgamma antagonist, GW9662, and the PKA inhibitor, H89, both inhibited UCP1
      expression stimulated by rosiglitazone and forskolin but PGC1alpha expression was
      not altered to the same extent. Reporter studies demonstrated that combined
      rosiglitazone and forskolin synergistically activated transcription from a full
      length 3.1 kbp UCP1 luciferase promoter construct, but the response was only
      additive and much reduced when a minimal 260 bp proximal UCP1 promoter was
      examined. Rosiglitazone and forskolin in combination were able to synergistically
      stimulate promoters comprising of tandem repeats of either PPREs or CREs. We
      conclude that rosiglitazone and forskolin act together to synergistically
      activate the UCP1 promoter directly rather than by increasing PGC1alpha
      expression and by a mechanism involving cross-talk between the signalling systems
      regulating the CRE and PPRE on the promoters.

PMID- 23554811
TI  - Acute diverticulitis in the young: the same disease in a different patient.
AB  - Background. Natural history and risk factors for diverticulitis in young patients
      are still debatable. This study aimed to assess whether difference exists in
      patients aged 50 and younger when compared to older patients and to identify risk
      factors for acute diverticulitis in the young. Patients and Methods. From January
      2006 to December 2011, 80 patients were admitted to our department for acute
      diverticulitis. We carried out a cross-sectional study in 23 patients (28.7%)
      aged 50 and younger and 57 older patients (71.3%). Results. Acute diverticulitis
      in the young was not more aggressive than in the older patient. Diverticulitis at
      patient's admission was similar with respect to Hinchey's stage and prior history
      of diverticulitis. No significant difference was found for both medical and
      surgical treatment. The rate of recurrent diverticulitis in nonoperated patients
      was similar. Male gender, body mass index >=25, and assumption of alcohol were
      independent risk factors for the occurrence of an acute diverticulitis in the
      young. Conclusions. The same disease seems to be affecting young patients such as
      overweight or obese male individual. Current policies to prevent diverticular
      disease and its related complications must include obesity control together with
      high-fiber diet and regular exercise.

PMID- 23554810
TI  - The Role of PPARs in Placental Immunology: A Systematic Review of the Literature.
AB  - Pregnancy is a state of immunotolerance, and pregnancy outcome is strongly linked
      to the correct activation and balancing of the maternal immune system. Besides
      abortion as possible result of improper early pregnancy development, other
      pregnancy associated conditions like preeclampsia (PE), intrauterine growth
      retardation (IUGR), preterm labour, or gestational diabetes mellitus (GDM) are
      linked to immunologic overactivation and dysregulation. Both the innate and the
      adaptive immune system, and therefore B and T lymphocytes, natural killer cells
      (NK), macrophages and dendritic cells (DCs) are all involved in trophoblast
      invasion, pregnancy maintenance, and development of pregnancy disorders.
      Peroxisome proliferator activated receptors (PPARs) are nuclear transcription
      factors with three known isotypes: PPARalpha, PPAR beta / delta , and PPAR gamma
      . They are expressed in most human organs and their function extends from
      regulating metabolism, homeostasis, and carcinogenesis to immune response. In the
      recent years, PPARs have been identified in most reproductive tissues and in all
      lines of immune cells. Only in few cases, the role of PPARs in reproductive
      immunology has been elucidated though the role of PPARs in immune answer and
      immunotolerance is evident. Within this paper we would like to give an update on
      today's knowledge about PPARs and immune cells in reproduction and highlight
      interesting interferences in regard of future therapeutic targets.

PMID- 23554812
TI  - Toxicologic assessment of a commercial decolorized whole leaf aloe vera juice,
      lily of the desert filtered whole leaf juice with aloesorb.
AB  - Aloe vera, a common ingredient in cosmetics, is increasingly being consumed as a
      beverage supplement. Although consumer interest in aloe likely stems from its
      association with several health benefits, a concern has also been raised by a
      National Toxicology Program Report that a nondecolorized whole leaf aloe vera
      extract taken internally by rats was associated with intestinal mucosal
      hyperplasia and ultimately malignancy. We tested a decolorized whole leaf (DCWL)
      aloe vera, treated with activated charcoal to remove the latex portion of the
      plant, for genotoxicity in bacteria, acute/subacute toxicity in B6C3F1 mice, and
      subchronic toxicity in F344 rats. We found this DCWL aloe vera juice to be
      nongenotoxic in histidine reversion and DNA repair assays. Following acute
      administration, mice exhibited no adverse signs at 3- or 14-day evaluation
      periods. When fed to male and female F344 rats over 13 weeks, DCWL aloe led to no
      toxicity as assessed by behavior, stools, weight gain, feed consumption, organ
      weights, and hematologic or clinical chemistry profiles. These rats had
      intestinal mucosal morphologies-examined grossly and microscopically-that were
      similar to controls. Our studies show that oral administration of this DCWL aloe
      juice has a different toxicology profile than that of the untreated aloe juice at
      exposures up to 13 weeks.

PMID- 23554813
TI  - Expression of Glutathione Peroxidase and Glutathione Reductase and Level of Free
      Radical Processes under Toxic Hepatitis in Rats.
AB  - Correlation between intensity of free radical processes estimated by
      biochemiluminesce parameters, content of lipoperoxidation products, and changes
      of glutathione peroxidase (GP, EC 1.11.1.9) and glutathione reductase (GR, EC
      1.6.4.2) activities at rats liver injury, after 12, 36, 70, 96, 110, and 125
      hours & tetrachloromethane administration have been investigated. The
      histological examination of the liver sections of rats showed that prominent
      hepatocytes with marked vacuolisation and inflammatory cells which were arranged
      around the necrotic tissue are more at 96 h after exposure to CCl4. Moreover
      maximum increase in GR and GP activities, 2.1 and 2.5 times, respectively, was
      observed at 96 h after exposure to CCl4, what coincided with the maximum of free
      radical oxidation processes. Using a combination of reverse transcription and
      real-time polymerase chain reaction, expression of the glutathione peroxidase and
      glutathione reductase genes (Gpx1 and Gsr) was analyzed by the determination of
      their respective mRNAs in the rat liver tissue under toxic hepatitis conditions.
      The analyses of Gpx1 and Gsr expression revealed that the transcript levels
      increased in 2.5- and 3.0-folds, respectively. Western blot analysis revealed
      that the amounts of hepatic Gpx1 and Gsr proteins increased considerably after
      CCl4 administration. It can be proposed that the overexpression of these enzymes
      could be a mechanism of enhancement of hepatocytes tolerance to oxidative stress.

PMID- 23554814
TI  - From 2D to 3D: Construction of a 3D Parametric Model for Detection of Dental
      Roots Shape and Position from a Panoramic Radiograph-A Preliminary Report.
AB  - Objectives. To build a 3D parametric model to detect shape and volume of dental
      roots, from a panoramic radiograph (PAN) of the patient. Materials and Methods. A
      PAN and a cone beam computed tomography (CBCT) of a patient were acquired. For
      each tooth, various parameters were considered (coronal and root lengths and
      widths): these were measured from the CBCT and from the PAN. Measures were
      compared to evaluate the accuracy level of PAN measurements. By using a CAD
      software, parametric models of an incisor and of a molar were constructed
      employing B-spline curves and free-form surfaces. PAN measures of teeth 2.1 and
      3.6 were assigned to the parametric models; the same two teeth were segmented
      from CBCT. The two models were superimposed to assess the accuracy of the
      parametric model. Results. PAN measures resulted to be accurate and comparable
      with all other measurements. From model superimposition the maximum error
      resulted was 1.1 mm on the incisor crown and 2 mm on the molar furcation.
      Conclusion. This study shows that it is possible to build a 3D parametric model
      starting from 2D information with a clinically valid accuracy level. This can
      ultimately lead to a crown-root movement simulation.

PMID- 23554815
TI  - Patellar osteoid osteoma as a cause of anterior knee pain in adolescents: a case
      report and literature review.
AB  - Anterior Knee Pain (AKP) is an important cause of complaint in adolescents which
      can suggest many possible diseases. Scientific literature concerning this complex
      symptom is wide and diversified. We report a rare case of patellar osteoid
      osteoma which affected a thirteen-year-old female who had suffered from anterior
      left knee pain for almost six months. The diagnosis was suspected from an
      accurate anamnesis, a careful clinical examination, and confirmed by imaging.
      Several minimally invasive techniques can be employed to treat osteoid osteoma.
      However, we consider CT-guided percutaneous drilling the safest and most
      effective procedure in case of patellar location. Despite its rarity, patellar
      osteoid osteoma ranges in the differential diagnosis for all patients suffering
      from AKP.

PMID- 23554817
TI  - Hippocampal neurogenesis and the brain repair response to brief stereotaxic
      insertion of a microneedle.
AB  - We tested the hypothesis that transient microinjury to the brain elicits cellular
      and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic
      insertion and removal of a microneedle into the right hippocampus resulted in (a)
      significantly increased expression of granulocyte-colony stimulating factor (G
      CSF), the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b)
      pronounced activation of microglia and astrocytes; and (c) increase in
      hippocampal neurogenesis. This study describes immediate and early humoral and
      cellular mechanisms of the brain's response to microinjury that will be useful
      for the investigation of potential neuroprotective and deleterious effects of
      deep brain stimulation in various neuropsychiatric disorders.

PMID- 23554818
TI  - Improved method for ex ovo-cultivation of developing chicken embryos for human
      stem cell xenografts.
AB  - The characterization of human stem cells for the usability in regenerative
      medicine is particularly based on investigations regarding their differentiation
      potential in vivo. In this regard, the chicken embryo model represents an ideal
      model organism. However, the access to the chicken embryo is only achievable by
      windowing the eggshell resulting in limited visibility and accessibility in
      subsequent experiments. On the contrary, ex ovo-culture systems avoid such
      negative side effects. Here, we present an improved ex ovo-cultivation method
      enabling the embryos to survive 13 days in vitro. Optimized cultivation of
      chicken embryos resulted in a normal development regarding their size and weight.
      Our ex ovo-approach closely resembles the development of chicken embryos in ovo,
      as demonstrated by properly developed nervous system, bones, and cartilage at
      expected time points. Finally, we investigated the usability of our method for
      trans-species transplantation of adult stem cells by injecting human neural crest
      derived stem cells into late Hamburger and Hamilton stages (HH26-HH28/E5-E6) of
      ex ovo-incubated embryos. We demonstrated the integration of human cells allowing
      experimentally easy investigation of the differentiation potential in the proper
      developmental context. Taken together, this ex ovo-method supports the prolonged
      cultivation of properly developing chicken embryos enabling integration studies
      of xenografted mammalian stem cells at late developmental stages.

PMID- 23554816
TI  - Bone-marrow-derived mesenchymal stem cells for organ repair.
AB  - Mesenchymal stem cells (MSCs) are prototypical adult stem cells with the capacity
      for self-renewal and differentiation with a broad tissue distribution. MSCs not
      only differentiate into types of cells of mesodermal lineage but also into
      endodermal and ectodermal lineages such as bone, fat, cartilage and
      cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons,
      and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like
      population and can be isolated from different adult tissues, including bone
      marrow (BM), umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete
      factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair,
      stimulate proliferation and differentiation of endogenous tissue progenitors, and
      decrease inflammatory and immune reactions. In this paper, we focus on the role
      of BM-derived MSCs in organ repair.

PMID- 23554819
TI  - Reversible audiometric threshold changes in children with uncomplicated malaria.
AB  - Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs,
      is associated with hearing impairment in adults. There is little information,
      however, on the extent, if any, of this effect in children, and the evidence
      linking artemisinin combination therapies (ACTs) with hearing is inconclusive.
      Methods. Audiometry was conducted in children with uncomplicated malaria treated
      with artesunate-amodiaquine (n = 37), artemether-lumefantrine (n = 35), or
      amodiaquine (n = 8) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days
      later and after 9 months. Audiometric thresholds were compared with those of a
      control group of children (n = 57) from the same area. Findings. During the acute
      stage, hearing threshold levels of treated children were significantly elevated
      compared with controls (P < 0.001). The threshold elevations persisted up to 28
      days, but no differences in hearing thresholds were evident between treated
      children and controls after 9 months. The hearing thresholds of children treated
      with the two ACT regimens were comparable but lower than those of amodiaquine
      treated children during acute illness. Interpretation. Malaria is the likely
      cause of the elevated hearing threshold levels during the acute illness, a
      finding that has implications for learning and development in areas of intense
      transmission, as well as for evaluating potential ototoxicity of new antimalarial
      drugs.

PMID- 23554821
TI  - Application of Glycyrrhiza glabra root as a novel adsorbent in the removal of
      toluene vapors: equilibrium, kinetic, and thermodynamic study.
AB  - The aim of this paper is to investigate the removal of toluene from gaseous
      solution through Glycyrrhiza glabra root (GGR) as a waste material. The batch
      adsorption experiments were conducted at various conditions including contact
      time, adsorbate concentration, humidity, and temperature. The adsorption capacity
      was increased by raising the sorbent humidity up to 50 percent. The adsorption of
      toluene was also increased over contact time by 12 h when the sorbent was
      saturated. The pseudo-second-order kinetic model and Freundlich model fitted the
      adsorption data better than other kinetic and isotherm models, respectively. The
      Dubinin-Radushkevich (D-R) isotherm also showed that the sorption by GGR was
      physical in nature. The results of the thermodynamic analysis illustrated that
      the adsorption process is exothermic. GGR as a novel adsorbent has not previously
      been used for the adsorption of pollutants.

PMID- 23554820
TI  - Antimicrobial lactoferrin peptides: the hidden players in the protective function
      of a multifunctional protein.
AB  - Lactoferrin is a multifunctional, iron-binding glycoprotein which displays a wide
      array of modes of action to execute its primary antimicrobial function. It
      contains various antimicrobial peptides which are released upon its hydrolysis by
      proteases. These peptides display a similarity with the antimicrobial cationic
      peptides found in nature. In the current scenario of increasing resistance to
      antibiotics, there is a need for the discovery of novel antimicrobial drugs. In
      this context, the structural and functional perspectives on some of the
      antimicrobial peptides found in N-lobe of lactoferrin have been reviewed. This
      paper provides the comparison of lactoferrin peptides with other antimicrobial
      peptides found in nature as well as interspecies comparison of the structural
      properties of these peptides within the native lactoferrin.

PMID- 23554823
TI  - Platelets and inflammatory markers in patients with gastric cancer.
AB  - The aim of the study was to assess the contribution of platelets and inflammatory
      markers in gastric cancer. We studied 50 patients. Taking into consideration the
      advancement of gastric cancer, patients were divided into 3 groups. Group (E)--13
      patients with early gastric cancer, group (A)--18 patients with regionally
      advanced cancer, and group (M)--19 patients with metastatic cancer. The
      determinations were performed twice prior to surgery and after surgery. In
      patients with gastric cancer, there is an increase in IL-6 and IL-23 compared
      with the healthy group. The highest values of IL-6 were obtained in early cancer
      (more than 8-fold increase), which seems to confirm the presence of acute
      inflammation. The lowest value of both of these cytokines was obtained in
      patients with metastatic cancer. In all patients, regardless of tumor stage,
      there was an increase in the concentration of CRP. An increase of PLT, higher
      proportion of the percentage of large platelets (LPLT), and increased mean
      platelet volume (MPV) were observed in the process of disease development. A
      positive correlation between MPV and LPLT and the accompanying decrease in the
      concentration of proinflammatory cytokines indicates the presence of an existing
      relationship between the platelet morphological parameters and the inflammation
      process in the development of gastric cancer.

PMID- 23554822
TI  - Prevalence of hepatitis d in the eastern mediterranean region: systematic review
      and meta analysis.
AB  - BACKGROUND: Hepatitis D Virus (HDV) causes the most threatening form of chronic
      viral hepatitis. To date, there is no overall estimation of HDV prevalence in the
      Eastern Mediterranean Region Office of WHO (EMRO) countries. OBJECTIVES: To
      provide a clear estimation of HDV prevalence in the aforementioned region.
      PATIENTS AND METHODS: In the current systematic review, databases such as PubMed,
      Embase, Web of sciences and Google scholar were searched Until December 2010. The
      summary estimate of HDV prevalence in the EMRO region was calculated as an
      average of the pooled infection prevalence of each country weighted by the ratio
      of the country's HBV population to the study's sample size in the survey data
      analysis. RESULTS: We included 62 eligible studies. The weighted mean of HDV
      prevalence in the EMRO region was 14.74% (95% CI: 14.73 - 14.77), 27.8% (95% CI:
      27.78 - 27.82), 36.57% (95% CI: 36.55 - 36.59) and 16.44%. (95% CI: 16.42 -
      16.46) in asymptomatic HBsAg positive carriers, chronic hepatitis patients,
      cirrhosis/ hepatocellular carcinoma, and high risk group, respectively. Among the
      asymptomatic HBsAg positive group, HDV prevalence was increased by years in older
      patients in Saudi Arabia but its prevalence was decreased in Iran. No specific
      pattern was seen according to chronological analysis during years among the EMRO
      countries. CONCLUSIONS: HDV infection is endemic in the EMRO countries and it is
      more common among patients with severe forms of hepatitis. Due to the high HDV
      infection rates in the EMRO countries, we recommend blood screening for HDV
      infection in this region.

PMID- 23554825
TI  - A randomized clinical trial of auricular point acupressure for chronic low back
      pain: a feasibility study.
AB  - Objectives. This prospective, randomized clinical trial (RCT) was designed to
      investigate the feasibility and effects of a 4-week auricular point acupressure
      (APA) for chronic low back pain (CLBP). Methods. Participants were randomized to
      either true APA (true acupoints with taped seeds on the designated ear points for
      CLBP) or sham APA (sham acupoints with taped seeds but on different locations
      than those designated for CLBP). The duration of treatment was four weeks.
      Participants were assessed before treatment, weekly during treatment, and 1 month
      following treatment. Results. Participants in the true APA group who completed
      the 4-week APA treatment had a 70% reduction in worst pain intensity, a 75%
      reduction in overall pain intensity, and a 42% improvement in disability due to
      back pain from baseline assessment. The reductions of worst pain and overall pain
      intensity in the true APA group were statistically greater than participants in
      the sham group (P < 0.01) at the completion of a 4-week APA and 1 month followup.
      Discussion. The preliminary findings of this feasibility study showed a reduction
      in pain intensity and improvement in physical function suggesting that APA may be
      a promising treatment for patients with CLBP.

PMID- 23554824
TI  - Practical Considerations For Developing Nucleoside Reverse Transcriptase
      Inhibitors.
AB  - Nucleoside reverse transcriptase inhibitors (NRTI) remain a cornerstone of
      current antiretroviral regimens in combinations usually with a non-nucleoside
      reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an
      integrase inhibitor (INI). The antiretroviral efficacy and relative safety of
      current NRTI results from a tight and relatively specific binding of their
      phosphorylated nucleoside triphosphates (NRTI-TP) with the HIV-1 reverse
      transcriptase which is essential for replication. The intracellular stability of
      NRTI-TP produces a sustained antiviral response, which makes convenient dosing
      feasible. Lessons learned regarding NRTI pharmacology screening, development, and
      use are discussed. NRTI and prodrugs currently under clinical development are
      outlined.

PMID- 23554826
TI  - Chinese medicinal herbs for childhood pneumonia: a systematic review of
      effectiveness and safety.
AB  - Objective. To assess the efficacy and safety of Chinese medicinal herbs for
      Childhood Pneumonia. Methods. We included randomized controlled trials (RCTs).
      The searched electronic databases included PubMed, the Cochrane Central Register
      of Controlled Trials, EMBASE, CBM, CNKI, and VIP. All studies included were
      assessed for quality and risk bias. Review Manager 5.1.6 software was used for
      data analyses, and the GRADEprofiler software was applied to classify the
      systematic review results. Results. Fourteen studies were identified (n = 1.824).
      Chinese herbs may increase total effective rate (risk ratio (RR) 1.18; 95%
      confidence interval (CI), 1.11-1.26) and improve cough (total mean difference
      (MD), -2.18; 95% CI, (-2.66)-(-1.71)), fever (total MD, -1.85; 95% CI, (-2.29)-(
      1.40)), rales (total MD, -1.53; 95% CI, (-1.84)-(-1.23)), and chest films (total
      MD, -3.10; 95% CI, (-4.11)-(-2.08)) in Childhood Pneumonia. Chinese herbs may
      shorten the length of hospital stay (total MD, -3.00; 95% CI, (-3.52)-(-2.48)),
      but no significant difference for adverse effects (RR, 0.39; 95% CI, 0.09-1.72)
      was identified. Conclusion. Chinese herbs may increase total effective rate and
      improve symptoms and signs. However, large, properly randomized, placebo
      controlled, double-blind studies are required.

PMID- 23554827
TI  - Syndrome differentiation in chinese herbal medicine for irritable bowel syndrome:
      a literature review of randomized trials.
AB  - Traditional Chinese medicine (TCM) has been commonly used for irritable bowel
      syndrome (IBS). Syndrome differentiation is one of the important characteristics
      of TCM. To assess the application and basic characteristics of syndrome
      differentiation in randomized controlled trials (RCTs) of Chinese herbal medicine
      for IBS, we performed this paper. We conducted electronic searches in main
      Chinese and English databases till March 2012. A total of 735 RCTs involving
      67,784 IBS participants were included. 224 (30.5%) studies applied syndrome
      differentiation. The major syndromes of IBS patients were the syndrome of liver
      stagnation and spleen deficiency (56.8%), spleen-stomach weakness (49.4%), spleen
      kidney yang deficiency (48.1%), and cold and heat in complexity (29.6%). Herbal
      formulas were prescribed based on syndrome differentiation in 202 studies.
      Chinese patent medicine was more commonly used in studies that only enrolled
      patients with a specific syndrome. 15 studies compared the therapeutic effect
      among different syndromes, of which 6 studies showed that there were significant
      differences among different syndromes. The low use of TCM syndrome
      differentiation in randomized trials of Chinese herbal medicine for IBS results
      in the poor pertinence of treatment. TCM syndrome differentiation should be used
      in further studies at the stage of recruitment, treatment, and data analyses.

PMID- 23554828
TI  - Inflammatory Regulation Effect and Action Mechanism of Anti-Inflammatory
      Effective Parts of Housefly (Musca domestica) Larvae on Atherosclerosis.
AB  - The protein-enriched extracts of housefly larvae were segregated by gel
      filtration chromatography (GFC) and then anti-inflammatory activity screening in
      RAW264.7 (induced by LPS) was carried out. After acquire the anti-inflammatory
      effective parts, its anti-atherosclerotic properties in vivo were then evaluated.
      Results showed that the anti-inflammatory effective parts of housefly larvae were
      low-molecular-weight parts. After treated with the effective parts oral gavaged
      for 4 weeks, the atherosclerotic lesions of the mouse were significantly
      decreased. The inflammatory and lipid parameters were also reduced (except HDL
      which was increased). Western blot analysis demonstrated that the effective parts
      exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm.
      The results of immunofluorescence microscopy analysis also showed that the
      expressions of p65 both in cytoplasm and nucleus were significantly reduced. The
      hypothesis that the anti-inflammatory effective parts of housefly larvae
      possessed anti-atherosclerosis activity in mouse and the possible mechanism could
      be associated with the inhibition of expression and nuclear transfer of NF- kappa
      B p65 could be derived.

PMID- 23554829
TI  - Neurite Outgrowth in PC12 Cells Stimulated by Components from Dendranthema *
      grandiflorum cv. "Mottenohoka" Is Enhanced by Suppressing Phosphorylation of
      p38MAPK.
AB  - Components from Dendranthema * grandiflorum cv. "Mottenohoka" that promote
      neurite outgrowth of PC12 cells were identified and the mechanism of neurite
      outgrowth stimulated by isolated components was studied. Components that promoted
      the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) of
      PC12 cells were isolated. From various structural analyses, the active components
      were identified as acacetin and luteolin. The effects of acacetin or luteolin on
      PC12 cells were evaluated by electro-blotting and immunostaining. Slight neurite
      outgrowth in PC12 cells was observed within 2 days of culture after stimulation
      by luteolin or acacetin. However, NGF-stimulation induced remarkable neurite
      outgrowth in comparison. Neurite outgrowth by luteolin or acacetin was
      significantly enhanced by pretreatment with SB203580 (a p38MAPK inhibitor). The
      results of this study into the phosphorylation of ERK 1/2 and p38MAPK by
      flavonoids suggest that the inhibition of p38MAPK phosphorylation may effectively
      enhance neurite outgrowth.

PMID- 23554830
TI  - Saikosaponin a Enhances Transient Inactivating Potassium Current in Rat
      Hippocampal CA1 Neurons.
AB  - Saikosaponin a (SSa), a main constituent of the Chinese herb Bupleurum chinense
      DC., has been demonstrated to have antiepileptic activity. Recent studies have
      shown that SSa could inhibit NMDA receptor current and persistent sodium current.
      However, the effects of SSa on potassium (K(+)) currents remain unclear. In this
      study, we tested the effect of SSa on 4AP-induced epileptiform discharges and
      K(+) currents in CA1 neurons of rat hippocampal slices. We found that SSa
      significantly inhibited epileptiform discharges frequency and duration in
      hippocampal CA1 neurons in the 4AP seizure model in a dose-dependent manner with
      an IC 50 of 0.7  MU M. SSa effectively increased the amplitude of I Total and I A
      , significantly negative-shifted the activation curve, and positive-shifted
      steady-state curve of I A . However, SSa induced no significant changes in the
      amplitude and activation curve of I K . In addition, SSa significantly increased
      the amplitude of 4AP-sensitive K(+) current, while there was no significant
      change in the amplitude of TEA-sensitive K(+) current. Together, our data
      indicate that SSa inhibits epileptiform discharges induced by 4AP in a dose
      dependent manner and that SSa exerts selectively enhancing effects on I A . These
      increases in I A may contribute to the anticonvulsant mechanisms of SSa.

PMID- 23554831
TI  - A laboratory evaluation of medicinal herbs used in china for the treatment of
      hand, foot, and mouth disease.
AB  - Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of
      hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China,
      medicinal herbals and preparations containing herbal extracts have demonstrated
      therapeutic efficacy with relative safety profiles. There have been no
      microbiological studies to validate their usefulness for HFMD. We selected 12
      commonly used herbs for HFMD from government recommended guidelines as well as
      published reports and tested for their antiviral activity and anti-inflammatory
      activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71
      infection significantly and was marginally active against CVA16 infection. The
      IC50 (concentration to have 50% inhibitory effect) values of HCT against a Fuyang
      strain and a BrCr strain of EV71 were determined at 8.9  MU g/mL and 20.6  MU
      g/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active
      against CVA16, with an IC50 value of 70.3  MU g/mL. The extract did not exhibit
      activity against EV71 infection. Although the majority of the extracts showed no
      activity against viral infection, several extracts demonstrated activity in
      blocking proinflammatory response by viral infection. This study therefore
      validates the effectiveness of Chinese herbs for HFMD since some formulations
      containing the correct combination of the herbs can block viral replication as
      well as proinflammatory response of HFMD.

PMID- 23554832
TI  - Circulating miR-583 and miR-663 Refer to ZHENG Differentiation in Chronic
      Hepatitis B.
AB  - Traditional Chinese medicine (TCM) ZHENG as the key pathological principle is to
      understand the human homeostasis and guide TCM treatment. Here, circulating
      microRNAs (miRNAs) were utilized to differentiate between ZHENGs including liver
      gallbladder dampness-heat syndrome (LGDHS) and liver-kidney yin deficiency
      syndrome (LKYDS) in chronic hepatitis B (CHB). Sera samples of CHB patients with
      LGDHS (n = 35), LKYDS (n = 24), and healthy controls (Ctrls, n = 21) were
      analyzed by microarray and real-time RT-PCR. Receiver-operator characteristic
      (ROC) curves were established to evaluate the levels of serum miRNA for
      discriminating LGDHS and LKYDS. The target genes of miRNAs were predicted by
      TargetScan. Gene Ontology (GO) and pathways were analyzed using DAVID tool. The
      results showed that 22 miRNAs were differentially expressed between LGDHS and
      LKYDS (fold change >2.0 and P < 0.01). Circulating miR-583 and miR-663 were
      significantly higher (P < 0.001) in CHB patients with LGDHS than those with LKYDS
      and Ctrls. ROC curve analysis revealed that miR-583 and miR-663 were sensitive
      and specific enough to distinguish LGDHS from LKYDS. Pathway enrichment analysis
      indicated that 354 putative targets for miR-583 and 68 putative targets for miR
      663 were mainly involved in Axon guidance, Neurotrophin, and MAPK signaling
      pathway. miR-583 and miR-663 may be potential markers for ZHENG differentiation
      in CHB.

PMID- 23554833
TI  - Exploring antiurolithic effects of gokshuradi polyherbal ayurvedic formulation in
      ethylene-glycol-induced urolithic rats.
AB  - Gokshuradi Yog (GY) is a polyherbal ayurvedic formulation used traditionally for
      several decades in India for the treatment of urolithiasis. The aim of the
      present study was to determine the underlying mechanism of GY action in the
      management of calcium oxalate urolithiasis. The effect of Gokshuradi polyherbal
      aqueous extracts (GPAEs) was studied on various biochemical parameters involved
      in calcium oxalate formation by employing in vitro and in vivo methods. GPAE
      exhibited significant antioxidant activity against 1, 1-diphenyl-2-picrylhydrazyl
      free radical and inhibited lipid peroxidation in the in vitro experiments. The
      rat model of urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium
      chloride (AC) in water caused polyuria, weight loss, impairment of renal
      function, and oxidative stress and decreased antioxidant enzyme activities in
      untreated control groups. However, GPAE- (25, 50, and 100 mg/kg) treated groups
      caused diuresis accompanied by a saluretic effect and revealed significant
      increase in antioxidant enzyme activities along with decreased oxalate
      synthesizing biochemical parameters at higher doses. This study revealed the
      antiurolithic effect of GPAE mediated possibly through inhibiting biochemical
      parameters involved in calcium oxalate formation, along with its diuretic and
      antioxidant effects, hence supporting its use in the treatment of calcium oxalate
      urolithiasis.

PMID- 23554834
TI  - Brazilein from Caesalpinia sappan L. Antioxidant Inhibits Adipocyte
      Differentiation and Induces Apoptosis through Caspase-3 Activity and Anthelmintic
      Activities against Hymenolepis nana and Anisakis simplex.
AB  - Brazilein, a natural, biologically active compound from Caesalpinia sappan L.,
      has been shown to exhibit anti-inflammatory and antioxidant properties and to
      inhibit the growth of several cancer cells. This study verifies the antioxidant
      and antitumor characteristics of brazilein in skin cancer cells and is the first
      time to elucidate the inhibition mechanism of adipocyte differentiation,
      cestocidal activities against Hymenolepis nana, and reduction of spontaneous
      movement in Anisakis simplex. Brazilein exhibits an antioxidant capacity as well
      as the ability to scavenge DPPH(*) and ABTS(*+) free radicals and to inhibit
      lipid peroxidation. Brazilein inhibited intracellular lipid accumulation during
      adipocyte differentiation in 3T3-L1 cells and suppressed the induction of
      peroxisome proliferator-activated receptor gamma (PPAR gamma ), the master
      regulator of adipogenesis, suggesting that brazilein presents the antiobesity
      effects. The toxic effects of brazilein were evaluated in terms of cell
      viability, induction of apoptosis, and the activity of caspase-3 in BCC cells.
      The inhibition of the growth of skin cancer cells (A431, BCC, and SCC25) by
      brazilein is greater than that of human skin malignant melanoma (A375) cells,
      mouse leukemic monocyte macrophage (RAW 264.7 cells), and noncancerous cells
      (HaCaT and BNLCL2 cells). The anthelmintic activities of brazilein against
      Hymenolepis nana are better than those of Anisakis simplex.

PMID- 23554835
TI  - The effects of high-dose qinggan huoxue recipe on acute liver failure induced by
      d-galactosamine in rats.
AB  - Qinggan Huoxue Recipe is a traditional Chinese medicine, which has been usually
      used to improve liver function in hepatitis. In order to investigate the effects
      of high-dose Qinggan Huoxue Recipe on acute liver failure and explore the
      potential mechanism, we had built acute liver failure models in rats by
      intraperitoneal injection of D-galactosamine (D-GalN). High-dose Qinggan Huoxue
      Recipe was delivered by gavage. After treatment, the blood alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL),
      albumin (ALB), cholinesterase (CHE), and prothrombin time (PT) were determined.
      The pathological score of liver tissue was recorded. Proliferating cell nuclear
      antigen (PCNA) immunohistochemistry staining and fluorescence quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) of high mobility group
      box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF- kappa B),
      and Caspase-3 were performed. The survival curve was also depicted. Our results
      demonstrated that high-dose Qinggan Huoxue Recipe could significantly improve
      liver function and increase survival rates in rats with acute liver failure.
      These effects were supposed to be mediated by suppressing inflammatory reaction
      and apoptosis.

PMID- 23554836
TI  - Tae-eum type as an independent risk factor for obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is prevalent and associated with several kinds of
      chronic diseases. There has been evidence that a specific type of Sasang
      constitution is a risk factor for metabolic and cardiovascular diseases that can
      be found in patients with OSA, but there are no studies that address the
      association between the Sasang constitution type (SCT) and OSA. The purpose of
      this study was to investigate the association between the SCT and OSA. A total of
      652 participants were included. All participants were examined for demographic
      information, medical history, and completed an interviewer-administered
      questionnaire on life style and sleep-related variables. Biochemical analyses
      were performed to determine the glucose and lipid profiles. An objective
      recording of OSA was done with an unattended home PSG using an Embla portable
      device. The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were
      significantly higher in the Tae-eum (TE) type as compared to the So-eum (SE) and
      the So-yang (SY) types. Even after adjusting for confounding variables, the TE
      type still had a 2.34-fold (95% CI, 1.11-4.94; P = 0.0262) increased risk for
      OSA. This population-based cohort study found that the TE constitutional type is
      an independent risk factor for the development of OSA.

PMID- 23554838
TI  - Noninvasive measurement of conductivity anisotropy at larmor frequency using MRI.
AB  - Anisotropic electrical properties can be found in biological tissues such as
      muscles and nerves. Conductivity tensor is a simplified model to express the
      effective electrical anisotropic information and depends on the imaging
      resolution. The determination of the conductivity tensor should be based on Ohm's
      law. In other words, the measurement of partial information of current density
      and the electric fields should be made. Since the direct measurements of the
      electric field and the current density are difficult, we use MRI to measure their
      partial information such as B1 map; it measures circulating current density and
      circulating electric field. In this work, the ratio of the two circulating
      fields, termed circulating admittivity, is proposed as measures of the
      conductivity anisotropy at Larmor frequency. Given eigenvectors of the
      conductivity tensor, quantitative measurement of the eigenvalues can be achieved
      from circulating admittivity for special tissue models. Without eigenvectors,
      qualitative information of anisotropy still can be acquired from circulating
      admittivity. The limitation of the circulating admittivity is that at least two
      components of the magnetic fields should be measured to capture anisotropic
      information.

PMID- 23554837
TI  - Thresholded two-phase test sample representation for outlier rejection in
      biological recognition.
AB  - The two-phase test sample representation (TPTSR) was proposed as a useful
      classifier for face recognition. However, the TPTSR method is not able to reject
      the impostor, so it should be modified for real-world applications. This paper
      introduces a thresholded TPTSR (T-TPTSR) method for complex object recognition
      with outliers, and two criteria for assessing the performance of outlier
      rejection and member classification are defined. The performance of the T-TPTSR
      method is compared with the modified global representation, PCA and LDA methods,
      respectively. The results show that the T-TPTSR method achieves the best
      performance among them according to the two criteria.

PMID- 23554840
TI  - A general framework for modeling sub- and ultraharmonics of ultrasound contrast
      agent signals with MISO volterra series.
AB  - Sub- and ultraharmonics generation by ultrasound contrast agents makes possible
      sub- and ultraharmonics imaging to enhance the contrast of ultrasound images and
      overcome the limitations of harmonic imaging. In order to separate different
      frequency components of ultrasound contrast agents signals, nonlinear models like
      single-input single-output (SISO) Volterra model are used. One important
      limitation of this model is its incapacity to model sub- and ultraharmonic
      components. Many attempts are made to model sub- and ultraharmonics using
      Volterra model. It led to the design of mutiple-input singe-output (MISO)
      Volterra model instead of SISO Volterra model. The key idea of MISO modeling was
      to decompose the input signal of the nonlinear system into periodic subsignals at
      the subharmonic frequency. In this paper, sub- and ultraharmonics modeling with
      MISO Volterra model is presented in a general framework that details and explains
      the required conditions to optimally model sub- and ultraharmonics. A new
      decomposition of the input signal in periodic orthogonal basis functions is
      presented. Results of application of different MISO Volterra methods to model
      simulated ultrasound contrast agents signals show its efficiency in sub- and
      ultraharmonics imaging.

PMID- 23554839
TI  - patGPCR: a multitemplate approach for improving 3D structure prediction of
      transmembrane helices of G-protein-coupled receptors.
AB  - The structures of the seven transmembrane helices of G-protein-coupled receptors
      are critically involved in many aspects of these receptors, such as receptor
      stability, ligand docking, and molecular function. Most of the previous
      multitemplate approaches have built a "super" template with very little merging
      of aligned fragments from different templates. Here, we present a parallelized
      multitemplate approach, patGPCR, to predict the 3D structures of transmembrane
      helices of G-protein-coupled receptors. patGPCR, which employs a bundle-packing
      related energy function that extends on the RosettaMem energy, parallelizes eight
      pipelines for transmembrane helix refinement and exchanges the optimized helix
      structures from multiple templates. We have investigated the performance of
      patGPCR on a test set containing eight determined G-protein-coupled receptors.
      The results indicate that patGPCR improves the TM RMSD of the predicted models by
      33.64% on average against a single-template method. Compared with other homology
      approaches, the best models for five of the eight targets built by patGPCR had a
      lower TM RMSD than that obtained from SWISS-MODEL; patGPCR also showed lower
      average TM RMSD than single-template and multiple-template MODELLER.

PMID- 23554841
TI  - Robust myocardial motion tracking for echocardiography: variational framework
      integrating local-to-global deformation.
AB  - This paper proposes a robust real-time myocardial border tracking algorithm for
      echocardiography. Commonly, after an initial contour of LV border is traced at
      one or two frames from the entire cardiac cycle, LV contour tracking is performed
      over the remaining frames. Among a variety of tracking techniques, optical flow
      method is the most widely used for motion estimation of moving objects. However,
      when echocardiography data is heavily corrupted in some local regions, the errors
      bring the tracking point out of the endocardial border, resulting in distorted LV
      contours. This shape distortion often occurs in practice since the data
      acquisition is affected by ultrasound artifacts, dropouts, or shadowing phenomena
      of cardiac walls. The proposed method is designed to deal with this shape
      distortion problem by integrating local optical flow motion and global
      deformation into a variational framework. The proposed descent method controls
      the individual tracking points to follow the local motions of a specific speckle
      pattern, while their overall motions are confined to the global motion constraint
      being approximately an affine transform of the initial tracking points. Many real
      experiments show that the proposed method achieves better overall performance
      than conventional methods.

PMID- 23554842
TI  - Bipolar plasma vaporization versus standard transurethral resection in secondary
      bladder neck sclerosis: a prospective, medium-term, randomized comparison.
AB  - OBJECTIVES: This prospective, randomized, medium-term trial aimed to assess the
      efficiency, safety and postoperative results of bipolar plasma vaporization (BPV)
      in comparison with monopolar transurethral resection (TUR) in cases of secondary
      bladder neck sclerosis (BNS). METHODS: A total of 70 patients with BNS secondary
      to transurethral resection of the prostate (TURP; 46 cases), open prostatectomy
      for benign prostatic hypertrophy (BPH; 18 cases) and radical prostatectomy for
      prostate cancer (6 cases) were enrolled in the trial. The inclusion criteria
      consisted of maximum flow rate (Q max) <10 ml/s and International Prostate
      Symptom Score (IPSS) >19. All patients were evaluated preoperatively and at 1, 3,
      6, 12 and 18 months after surgery by IPSS, quality of life score (QoL), Q max and
      postvoiding residual urinary volume (PVR). RESULTS: The mean operation time (10.3
      versus 14.9 minutes), catheterization period (0.75 versus 2.1 days) and hospital
      stay (1.1 versus 3.2 days) were significantly reduced in the BPV series. During
      the immediate postoperative follow up, recatheterization for acute urinary
      retention only occurred in the TUR series (5.7%). The medium-term retreatment
      requirements due to BNS recurrence were lower in the BPV study arm (2.8% versus
      8.5%). At the 1, 3, 6, 12 and 18 months assessments, statistically similar
      parameters were found concerning the IPSS and QoL symptom scores, Q max and PVR
      values specific for the two therapeutic alternatives. CONCLUSIONS: BPV
      constitutes a valuable endoscopic treatment approach for secondary BNS. The
      method emphasized superior efficacy, a satisfactory safety profile and similar
      medium-term follow-up features when compared with standard TUR.

PMID- 23554843
TI  - Increased expression of the androgen receptor with p300 and interleukin-6
      coactivators compensate for oligonucleotide suppression of bcl-2: no increased
      CREB binding protein or interleukin-4 expression.
AB  - BACKGROUND: Antisense oligonucleotides (oligos) have been employed against in
      vivo and in vitro prostate cancer models targeting growth regulatory proteins.
      While most oligos have targeted growth factors or their receptors, others have
      been directed against inhibitors of apoptosis and mediators of androgen action.
      We previously evaluated a set of oligos which targeted and comparably suppressed
      the expression of the apoptosis inhibitor protein bcl-2. LNCaP cells adapted to
      this restoration of apoptosis with suppression of caspase 3 (an apoptosis
      promoter) and an enhanced expression of the androgen receptor (AR), suggesting an
      increased sensitivity to androgens. METHODS AND RESULTS: In a continuation of
      this study, we evaluated the expression of AR coactivators p300, its homolog CREB
      binding protein (CREBBP) and cytokines interleukin (IL)-4 and IL-6, finding p300
      and IL-6 similarly enhanced. CONCLUSIONS: LNCaP cells are hormone sensitive and
      untreated cells express minimal p300 activity. Therefore, the enhanced expression
      which followed oligo treatment makes its induction more impressive and implies a
      pattern of gene expression more associated with later stage (androgen
      insensitive) disease. This suggests that oligo treatment directed against bcl-2
      can be evaded through compensatory changes in AR expression and some
      coactivators, promoting tumor growth, and may promote transformation of the tumor
      to a more aggressive phenotype.

PMID- 23554844
TI  - Shockwave treatment of erectile dysfunction.
AB  - Low-intensity extracorporeal shock wave therapy (LI-ESWT) is a novel modality
      that has recently been developed for treating erectile dysfunction (ED). Unlike
      other current treatment options for ED, all of which are palliative in nature, LI
      ESWT is unique in that it aims to restore the erectile mechanism in order to
      enable natural or spontaneous erections. Results from basic science experiments
      have provided evidence that LI-ESWT induces cellular microtrauma, which in turn
      stimulates the release of angiogenic factors and the subsequent
      neovascularization of the treated tissue. Extracorporeal shock wave therapy
      (ESWT) has been clinically investigated and applied in several medical fields
      with various degrees of success. High-intensity shock wave therapy is used for
      lithotripsy because of its focused mechanical destructive nature, and medium
      intensity shock waves have been shown to have anti-inflammatory properties and
      are used for treating a wide array of orthopedic conditions, such as non-union
      fractures, tendonitis, and bursitis. In contrast, LI-ESWT has angiogenetic
      properties and is therefore used in the management of chronic wounds, peripheral
      neuropathy, and in cardiac neovascularization. As a result of these
      characteristics we initiated a series of experiments evaluating the effect of LI
      ESWT on the cavernosal tissue of patients with vasculogenic ED. The results of
      our studies, which also included a double-blind randomized control trial, confirm
      that LI-ESWT generates a significant clinical improvement of erectile function
      and a significant improvement in penile hemodynamics without any adverse effects.
      Although further extensive research is needed, LI-ESWT may create a new standard
      of care for men with vasculogenic ED.

PMID- 23554845
TI  - Udenafil: efficacy and tolerability in the management of erectile dysfunction.
AB  - Udenafil is a potent novel phosphodiesterase-5 inhibitor approved for use in
      Korea. Udenafil has unique properties, with a T max of 1.0-1.5 h and a T 1/2 of
      11-13 h (a relatively rapid onset and a long duration of action). Therefore, both
      on-demand and once-daily use of udenafil have been reported. Udenafil's efficacy
      and tolerability have been evaluated in several studies, and recent and
      continuing studies have demonstrated udenafil's promise in both dosing regimens.
      Presently, tadalafil is the only FDA-approved drug for daily dosing, but udenafil
      can be used as a once-daily dose for erectile dysfunction patients who cannot
      tolerate tadalafil due to phosphodiesterase subtype selectivity. Udenafil as an
      on-demand or once-daily dose is effective and tolerable, but more studies are
      needed in patients of other ethnicities and with comorbid conditions such as
      diabetes mellitus, hypertension, and benign prostate hyperplasia.

PMID- 23554847
TI  - An evidence-based guide to the selection of sequential therapies in metastatic
      renal cell carcinoma.
AB  - Targeted therapies have introduced a paradigm shift in the management of
      metastatic renal cell carcinoma. Currently, four molecules (sunitinib, pazopanib,
      bevacizumab plus interferon, temsirolimus) are considered in first-line therapy,
      and three other molecules for second, or subsequent lines of therapy (everolimus,
      axitinib, sorafenib). In addition, other molecules and sequencing schemes are
      being tested in ongoing phase II/III studies. We conducted a systematic review
      using PubMed and several other databases up to December 2011 of prospective and
      retrospective studies on treatment management of metastatic renal cell carcinoma
      using targeted therapies, with a special focus on use of sequential treatment.
      Based on phase III data, the optimal sequencing scheme for patients with clear
      cell or even non-clear cell histological subtype appears to consist of sunitinib,
      followed by axitinib, followed by everolimus. Subsequent treatment options rely
      on lower evidence studies and could consist of fourth-line sorafenib or sunitinib
      rechallenge. Such therapies would qualify as last recourse options. In another
      context, temsirolimus may be used in patients who fulfill the Memorial Sloan
      Kettering Cancer Center poor risk criteria or who have poor performance status.
      We conclude that in the current setting, sequential therapy represents the
      cornerstone of effective management of metastatic renal cell carcinoma.

PMID- 23554846
TI  - The role of naftopidil in the management of benign prostatic hyperplasia.
AB  - Naftopidil, which to a certain extent shows an affinity to alpha1D-adrenoceptor
      subtype in addition to a high affinity to alpha1A-adrenoceptor, has been used for
      the treatment of benign prostatic obstruction and benign prostatic hyperplasia
      (BPH) associated lower urinary tract symptoms (LUTS). The aim of the present
      review is to systematically refer to the published studies on this unique agent
      for BPH. Based on a randomized prazosin-controlled study and another double-blind
      placebo-controlled study, which verified the dose-dependent effects of
      naftopidil, the Japanese Ministry of Health, Labor and Welfare approved
      naftopidil for treating men with BPH in 1996. Several tamsulosin-controlled
      studies have suggested treatment effects of naftopidil similar to those of
      tamsulosin and potentially higher efficacy for alleviating storage symptoms by
      naftopidil. Although well-designed, randomized studies are warranted to confirm
      the long-term outcomes and effector/target of naftopidil, the alpha1A-antagonist
      naftopidil, which also blocks alpha1D-adrenoceptor, improves voiding symptoms,
      and may also be useful for the management of men with storage symptoms
      represented by nocturia, retrieving their quality of life impaired by BPH
      associated LUTS.

PMID- 23554848
TI  - Relationships between tissue properties and operational parameters of a dental
      handpiece during simulated cavity preparation.
AB  - A preliminary study was conducted on the development of an intelligent dental
      handpiece with functionality to detect subtle changes in mechanical properties of
      tooth tissue during milling. Such equipment would be able to adopt changes in
      cutting parameters and make real-time measurements to avoid tooth tissue damage
      caused by overexertion and overextension of the cutting tool. A modified dental
      handpiece, instrumented with strain gauges, microphone, displacement sensor, and
      air pressure sensor, was mounted to a linear movement table and used to mill
      three to four cavities in >50 bovine teeth. Extracted sound frequency and density
      were analyzed along with force, air pressure, and displacement for correlations
      and trends. Experimental results showed a high correlation (coefficient close to
      0.7) between the feed force, the rotational frequency, and the averaged gray
      scale. These results could form the basis of a feedback control system to improve
      the safety of dental cutting procedures. This article is written in memory of Dr
      Hongyan Sun, who passed away in 2011 at a young age of 37.

PMID- 23554849
TI  - Effects of prolonged treatment with memantine in the MRL model of CNS lupus.
AB  - OBJECTIVES: Neuropsychiatric manifestations and brain atrophy of unknown etiology
      are common and severe complications of systemic lupus erythematosus (SLE). An
      autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been
      proposed as a key factor in the etiology of central nervous system (CNS) SLE.
      This hypothesis was supported by evidence suggesting memantine (MEM), an
      uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain
      pathology in healthy mice immunized with a peptide similar to an epitope on the
      NR2 receptor. Given that SLE is a chronic condition, we presently examine the
      effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE
      like disease. METHODS: A broad behavioral battery and 7-Tesla MRI were used to
      examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water)
      prevents CNS involvement in this spontaneous model of SLE. RESULTS: Although MEM
      increased novel object exploration in MRL/lpr mice, it did not show other
      beneficial, substrain-specific effects. Conversely, MEM was detrimental to
      spontaneous activity in control MRL +/+ mice and had a negative effect on body
      mass gain. Similarly, MRI revealed comparable increases in the volume of
      periventricular structures in MEM-treated groups. CONCLUSIONS: Sustained exposure
      to MEM affects body growth, brain morphology, and behavior primarily by
      pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific
      improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that
      the NMDA system is merely a constituent of a complex pathogenenic cascade.
      However, it was evident that chronic administration of MEM is unable to
      completely prevent the development of a CNS SLE-like syndrome.

PMID- 23554851
TI  - Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in
      human experimental pain: a randomized placebo-controlled study.
AB  - BACKGROUND AND AIMS: Compounds that act on GABA-receptors produce anti
      hyperalgesia in animal models, but little is known on their effects in humans.
      The aim of this study was to explore the potential usefulness of GABA-agonism for
      the control of pain in humans. Two agonists at the benzodiazepine-binding site of
      GABAA-receptors (clobazam and clonazepam) were studied using multiple
      experimental pain tests. Positive results would support further investigation of
      GABA agonism for the control of clinical pain. METHODS: In a randomized double
      blind crossover design, 16 healthy male volunteers received clobazam 20 mg,
      clonazepam 1 mg and tolterodine 1 mg (active placebo). The area of static
      hyperalgesia after intradermal capsaicin injection was the primary endpoint.
      Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair
      stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and
      intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation), and
      pain during cuff algometry. RESULTS: For the primary endpoint, an increase in the
      area of static hyperalgesia was observed after administration of placebo
      (p<0.001), but not after clobazam and clonazepam. Results suggestive for an anti
      hyperalgesic effect of the benzodiazepines were obtained with all three
      intramuscular pain models and with cuff algometry. No effect could be detected
      with the other pain models employed. CONCLUSIONS: Collectively, the results are
      suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA
      receptors in humans, particularly in models of secondary hyperalgesia and deep
      pain. The findings are not conclusive, but support further clinical research on
      pain modulation by GABAergic drugs. Because of the partial results, future
      research should focus on compounds acting selectively on subunits of the GABA
      complex, which may allow the achievement of higher receptor occupancy than
      unselective drugs. Our data also provide information on the most suitable
      experimental models for future investigation of GABAergic compounds. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01011036.

PMID- 23554853
TI  - The critical role of protein arginine methyltransferase prmt8 in zebrafish
      embryonic and neural development is non-redundant with its paralogue prmt1.
AB  - Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely
      distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of
      PRMT1 with an extra N-terminal sequence and brain-specific expression. We use
      zebrafish (Danio rerio) as a vertebrate model to study PRMT8 function and
      putative redundancy with PRMT1. The transcripts of zebrafish prmt8 were
      specifically expressed in adult zebrafish brain and ubiquitously expressed from
      zygotic to early segmentation stage before the neuronal development. Whole-mount
      in situ hybridization revealed ubiquitous prmt8 expression pattern during early
      embryonic stages, similar to that of prmt1. Knockdown of prmt8 with antisense
      morpholino oligonucleotide phenocopied prmt1-knockdown, with
      convergence/extension defects at gastrulation. Other abnormalities observed later
      include short body axis, curled tails, small and malformed brain and eyes.
      Catalytically inactive prmt8 failed to complement the morphants, indicating the
      importance of methyltransferase activity. Full-length prmt8 but not prmt1 cRNA
      can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with
      the N-terminus of Prmt8 can rescue the prmt8 morphants. In contrast, N-terminus-
      deleted but not full-length prmt8 cRNA can rescue the prmt1 morphants as
      efficiently as prmt1 cRNA. Abnormal brain morphologies illustrated with brain
      markers and loss of fluorescent neurons in a transgenic fish upon prmt8 knockdown
      confirm the critical roles of prmt8 in neural development. In summery, our study
      is the first report showing the expression and function of prmt8 in early
      zebrafish embryogenesis. Our results indicate that prmt8 may play important roles
      non-overlapping with prmt1 in embryonic and neural development depending on its
      specific N-terminus.

PMID- 23554852
TI  - The role of systematic reviews in pharmacovigilance planning and Clinical Trials
      Authorisation application: example from the SLEEPS trial.
AB  - BACKGROUND: Adequate sedation is crucial to the management of children requiring
      assisted ventilation on Paediatric Intensive Care Units (PICU). The evidence-base
      of randomised controlled trials (RCTs) in this area is small and a trial was
      planned to compare midazolam and clonidine, two sedatives widely used within
      PICUs neither of which being licensed for that use. The application to obtain a
      Clinical Trials Authorisation from the Medicines and Healthcare products
      Regulatory Agency (MHRA) required a dossier summarising the safety profiles of
      each drug and the pharmacovigilance plan for the trial needed to be determined by
      this information. A systematic review was undertaken to identify reports relating
      to the safety of each drug. METHODOLOGY/PRINCIPAL FINDINGS: The Summary of
      Product Characteristics (SmPC) were obtained for each sedative. The MHRA were
      requested to provide reports relating to the use of each drug as a sedative in
      children under the age of 16. Medline was searched to identify RCTs, controlled
      clinical trials, observational studies, case reports and series. 288 abstracts
      were identified for midazolam and 16 for clonidine with full texts obtained for
      80 and 6 articles respectively. Thirty-three studies provided data for midazolam
      and two for clonidine. The majority of data has come from observational studies
      and case reports. The MHRA provided details of 10 and 3 reports of suspected
      adverse drug reactions. CONCLUSIONS/SIGNIFICANCE: No adverse reactions were
      identified in addition to those specified within the SmPC for the licensed use of
      the drugs. Based on this information and the wide spread use of both sedatives in
      routine practice the pharmacovigilance plan was restricted to adverse reactions.
      The Clinical Trials Authorisation was granted based on the data presented in the
      SmPC and the pharmacovigilance plan within the clinical trial protocol
      restricting collection and reporting to adverse reactions.

PMID- 23554854
TI  - Assigning quantitative function to post-translational modifications reveals
      multiple sites of phosphorylation that tune yeast pheromone signaling output.
AB  - Cell signaling systems transmit information by post-translationally modifying
      signaling proteins, often via phosphorylation. While thousands of sites of
      phosphorylation have been identified in proteomic studies, the vast majority of
      sites have no known function. Assigning functional roles to the catalog of
      uncharacterized phosphorylation sites is a key research challenge. Here we
      present a general approach to address this challenge and apply it to a
      prototypical signaling pathway, the pheromone response pathway in Saccharomyces
      cerevisiae. The pheromone pathway includes a mitogen activated protein kinase
      (MAPK) cascade activated by a G-protein coupled receptor (GPCR). We used
      published mass spectrometry-based proteomics data to identify putative sites of
      phosphorylation on pheromone pathway components, and we used evolutionary
      conservation to assign priority to a list of candidate MAPK regulatory sites. We
      made targeted alterations in those sites, and measured the effects of the
      mutations on pheromone pathway output in single cells. Our work identified six
      new sites that quantitatively tuned system output. We developed simple
      computational models to find system architectures that recapitulated the
      quantitative phenotypes of the mutants. Our results identify a number of putative
      phosphorylation events that contribute to adjust the input-output relationship of
      this model eukaryotic signaling system. We believe this combined approach
      constitutes a general means not only to reveal modification sites required to
      turn a pathway on and off, but also those required for more subtle quantitative
      effects that tune pathway output. Our results suggest that relatively small
      quantitative influences from individual phosphorylation events endow signaling
      systems with plasticity that evolution may exploit to quantitatively tailor
      signaling outcomes.

PMID- 23554855
TI  - Outcomes of optimized over standard protocol of rabbit antithymocyte globulin for
      severe aplastic anemia: a single-center experience.
AB  - BACKGROUND: Previous reports showed that outcome of rabbit antithymocyte globulin
      (rATG) was not satisfactory as the first-line therapy for severe aplastic anemia
      (SAA). We explored a modifying schedule of administration of rATG. DESIGN AND
      METHODS: Outcomes of a cohort of 175 SAA patients, including 51 patients
      administered with standard protocol (3.55 mg/kg/d for 5 days) and 124 cases with
      optimized protocol (1.97 mg/kg/d for 9 days) of rATG plus cyclosporine (CSA),
      were analyzed retrospectively. RESULTS: Of all 175 patients, response rates at 3
      and 6 months were 36.6% and 56.0%, respectively. 51 cases received standard
      protocol had poor responses at 3 (25.5%) and 6 months (41.2%). However, 124
      patients received optimized protocol had better responses at 3 (41.1%, P = 0.14)
      and 6 (62.1%, P = 0.01). Higher incidences of infection (57.1% versus 37.9%, P =
      0.02) and early mortality (17.9% versus 0.8%, P<0.001) occurred in patients
      received standard protocol compared with optimized protocol. The 5-year overall
      survival in favor of the optimized over standard rATG protocol (76.0% versus.
      50.3%, P<0.001) was observed. By multivariate analysis, optimized protocol (RR =
      2.21, P = 0.04), response at 3 months (RR = 10.31, P = 0.03) and shorter interval
      (<23 days) between diagnosis and initial dose of rATG (RR = 5.35, P = 0.002) were
      independent favorable predictors of overall survival. CONCLUSIONS: Optimized
      instead of standard rATG protocol in combination with CSA remained efficacious as
      a first-line immunosuppressive regimen for SAA.

PMID- 23554856
TI  - Comparison of PfHRP-2/pLDH ELISA, qPCR and microscopy for the detection of
      plasmodium events and prediction of sick visits during a malaria vaccine study.
AB  - BACKGROUND: Compared to expert malaria microscopy, malaria biomarkers such as
      Plasmodium falciparum histidine rich protein-2 (PfHRP-2), and PCR provide
      superior analytical sensitivity and specificity for quantifying malaria parasites
      infections. This study reports on parasite prevalence, sick visits parasite
      density and species composition by different diagnostic methods during a phase-I
      malaria vaccine trial. METHODS: Blood samples for microscopy, PfHRP-2 and
      Plasmodium lactate dehydrogenase (pLDH) ELISAs and real time quantitative PCR
      (qPCR) were collected during scheduled (n = 298) or sick visits (n = 38) from 30
      adults participating in a 112-day vaccine trial. The four methods were used to
      assess parasite prevalence, as well as parasite density over a 42-day period for
      patients with clinical episodes. RESULTS: During scheduled visits, qPCR (39.9%, N
      = 119) and PfHRP-2 ELISA (36.9%, N = 110) detected higher parasite prevalence
      than pLDH ELISA (16.8%, N = 50) and all methods were more sensitive than
      microscopy (13.4%, N = 40). All microscopically detected infections contained P.
      falciparum, as mono-infections (95%) or with P. malariae (5%). By qPCR, 102/119
      infections were speciated. P. falciparum predominated either as monoinfections
      (71.6%), with P. malariae (8.8%), P. ovale (4.9%) or both (3.9%). P. malariae
      (6.9%) and P. ovale (1.0%) also occurred as co-infections (2.9%). As expected,
      higher prevalences were detected during sick visits, with prevalences of 65.8%
      (qPCR), 60.5% (PfHRP-2 ELISA), 21.1% (pLDH ELISA) and 31.6% (microscopy). PfHRP-2
      showed biomass build-up that climaxed (1813+/-3410 ng/mL SD) at clinical
      episodes. CONCLUSION: PfHRP-2 ELISA and qPCR may be needed for accurately
      quantifying the malaria parasite burden. In addition, qPCR improves parasite
      speciation, whilst PfHRP-2 ELISA is a potential predictor for clinical disease
      caused by P. falciparum. TRIAL REGISTRATION: ClinicalTrials.gov NCT00666380.

PMID- 23554857
TI  - Targeting CDH17 suppresses tumor progression in gastric cancer by downregulating
      Wnt/beta-catenin signaling.
AB  - PURPOSE: Gastric cancer remains one of the leading causes of cancer death
      worldwide. Patients usually present late with local invasion or metastasis, for
      which there are no effective therapies available. Following previous studies that
      identified the adhesion molecule Cadherin-17(CDH17) as a potential marker for
      gastric carcinoma, we performed proof-of-principle studies to develop rational
      therapeutic approaches targeting CDH17 for treating this disease. METHODS:
      Immunohistochemistry was used to study the expression of CDH17 in 156 gastric
      carcinomas, and the relationship between survival and CDH17 expression was
      studied by multivariate analyses. The effect of RNA interference-mediated
      knockdown of CDH17 on proliferation of gastric carcinoma cell lines was examined
      in vitro and in vivo, as well as the effects on downstream signaling by
      immunoblotting. RESULTS: CDH17 was consistently up-regulated in human gastric
      cancers, and overall survival in patients with CDH17 upregulation was poorer than
      in those without expression of this gene (5 yrs overall survival rate 29.0% vs.
      45.0%, P<0.01). Functional assays demonstrated that CDH17 knockdown inhibited
      cell proliferation, adhesion, migration, invasion, clonogenicity and induce G0/G1
      arrest. In mice, shRNA-mediated CDH17 knockdown markedly inhibits tumor growth;
      intratumoral injection of CDH17 shRNAs results in significant antitumor effects
      on transplanted tumor models. The antitumor mechanisms underlying CDH17
      inhibition involve inactivation of Wnt/beta-catenin signaling. CONCLUSION: Our
      results identify CDH17 as a biomarker of gastric carcinoma and attractive
      therapeutic target for this aggressive malignancy.

PMID- 23554858
TI  - The effect of cold temperature on increased exacerbation of chronic obstructive
      pulmonary disease: a nationwide study.
AB  - BACKGROUND: Seasonal variations in the acute exacerbation of chronic obstructive
      pulmonary disease (COPD) have been reported. However, the influence of air
      temperature and other meteorological factors on COPD exacerbation remains
      unclear. METHODS: National Health Insurance registry data from January 1, 1999 to
      December 1, 2009 and meteorological variables from the Taiwan Central Weather
      Bureau for the same period were analyzed. A case-crossover study design was used
      to investigate the association between COPD exacerbation and meteorological
      variables. RESULTS: A total of 16,254 cases who suffered from COPD exacerbation
      were enrolled. We found that a 1 degrees C decrease in air temperature was
      associated with a 0.8% increase in the exacerbation rate on event-days (95%
      confidence interval (CI), 1.015-1.138, p = 0.015). With a 5 degrees C decrease in
      mean temperature, the cold temperature (28-day average temperature) had a long
      term effect on the exacerbation of COPD (odds ratio (OR), 1.106, 95% CI 1.063
      1.152, p<0.001). In addition, elderly patients and those who did not receive
      inhaled medication tended to suffer an exacerbation when the mean temperature
      dropped 5 degrees C. Higher barometric pressure, more hours of sunshine, and
      lower humidity were associated with an increase in COPD exacerbation.
      CONCLUSIONS: This study demonstrated the effect of cold temperatures on the COPD
      exacerbation rate. Elderly patients and those without inhaled medicine before the
      exacerbation event were affected significantly by lower mean temperatures. A more
      comprehensive program to prevent cold stress in COPD patients may lead to a
      reduction in the exacerbations rate of COPD.

PMID- 23554859
TI  - Structure-guided systems-level engineering of oxidation-prone methionine residues
      in catalytic domain of an alkaline alpha-amylase from Alkalimonas amylolytica for
      significant improvement of both oxidative stability and catalytic efficiency.
AB  - High oxidative stability and catalytic efficiency are required for the alkaline
      alpha-amylases to keep the enzymatic performance under the harsh conditions in
      detergent industries. In this work, we attempted to significantly improve both
      the oxidative stability and catalytic efficiency of an alkaline alpha-amylase
      from Alkalimonas amylolytica by engineering the five oxidation-prone methionine
      residues around the catalytic domain via a systematic approach. Specifically,
      based on the tertiary structure analysis, five methionines (Met 145, Met 214, Met
      229, Met 247 and Met 317) were individually substituted with oxidation-resistant
      threonine, isoleucine and alaline, respectively. Among the created 15 mutants, 7
      mutants M145A, M145I, M214A, M229A, M229T, M247T and M317I showed significantly
      enhanced oxidative stability or catalytic efficiency. In previous work, we found
      that the replacement of M247 with leucine could significantly improve the
      oxidative stability. Thus, these 8 positive mutants (M145A, M145I, M214A, M229A,
      M229T, M247T, M247L and M317I) were used to conduct the second round of
      combinational mutations. Among the constructed 85 mutants (25 two-point mutants,
      36 three-point mutants, 16 four-point mutants and 8 five-point mutants), the
      mutant M145I-214A-229T-247T-317I showed a 5.4-fold increase in oxidative
      stability and a 3.0-fold increase in catalytic efficiency. Interestingly, the
      specific activity, alkaline stability and thermal stability of this mutant were
      also increased. The increase of salt bridge and hydrogen bonds around the
      catalytic domain contributed to the significantly improved catalytic efficiency
      and stability, as revealed by the three-dimensional structure model of wild-type
      alkaline alpha-amylase and its mutant M145I-214A-229T-247T-317I. With the
      significantly improved oxidative stability and catalytic efficiency, the mutant
      M145I-214A-229T-247T-317I has a great potential as a detergent additive, and this
      structure-guided systems engineering strategy may be useful for the protein
      engineering of the other microbial enzymes to fulfill industrial requirements.

PMID- 23554860
TI  - A mathematical model of chikungunya dynamics and control: the major epidemic on
      Reunion Island.
AB  - Chikungunya is a re-emerging arboviral disease transmitted by Aedes spp.
      mosquitoes. Although principally endemic to Africa and Asia, recent outbreaks
      have occurred in Europe following introductions by returning travellers. A
      particularly large outbreak occurred on Reunion Island in 2006, the published
      data from which forms the basis of the current study. A simple, deterministic
      mathematical model of the transmission of the virus between humans and mosquitoes
      was constructed and parameterised with the up-to-date literature on infection
      biology. The model is fitted to the large Reunion epidemic, resulting in an
      estimate of 4.1 for the type reproduction number of chikungunya. Although
      simplistic, the model provided a close approximation of both the peak incidence
      of the outbreak and the final epidemic size. Sensitivity analysis using Monte
      Carlo simulation demonstrated the strong influence that both the latent period of
      infection in humans and the pre-patent period have on these two epidemiological
      outcomes. We show why separating these variables, which are epidemiologically
      distinct in chikungunya infections, is not only necessary for accurate model
      fitting but also important in informing control.

PMID- 23554861
TI  - Interleukin-27 signaling promotes immunity against endogenously arising murine
      tumors.
AB  - Interleukin-27 (IL-27) is a pleiotropic cytokine but its immunosuppressive
      effects predominate during many in vivo immunological challenges. Despite this,
      evidence from tumor cell line transfer models suggested that IL-27 could promote
      immune responses in the tumor context. However, the role of IL-27 in immunity
      against tumors that develop in situ and in tumor immunosurveillance remain
      undefined. In this study, we demonstrate that tumor development and growth are
      accelerated in IL-27 receptor alpha (Il27ra)-deficient mice. Enhanced tumor
      growth in both carcinogen-induced fibrosarcoma and oncogene-driven mammary
      carcinoma was associated with decreased interferon-gamma production by CD4 and
      CD8 T cells and increased numbers of regulatory T-cells (Treg). This is the first
      study to show that IL-27 promotes protective immune responses against endogenous
      tumors, which is critical as the basis for future development of an IL-27 based
      therapeutic agent.

PMID- 23554862
TI  - Experimental adaptation of wild-type canine distemper virus (CDV) to the human
      entry receptor CD150.
AB  - Canine distemper virus (CDV), a close relative of measles virus (MV), is
      widespread and well known for its broad host range. When the goal of measles
      eradication may be achieved, and when measles vaccination will be stopped, CDV
      might eventually cross the species barrier to humans and emerge as a new human
      pathogen. In order to get an impression how fast such alterations may occur, we
      characterized required adaptive mutations to the human entry receptors CD150
      (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild
      type CDV-A75/17(red) adapted quickly to growth in human H358 epithelial cells
      expressing human nectin-4. Sequencing of the viral attachment proteins
      (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive
      alteration was required to utilize human nectin-4. In contrast, the virus
      replicated only to low titres (10(2) pfu/ml) in Vero cells expressing human CD150
      (Vero-hSLAM). After three passages using these cells virus was adapted to human
      CD150 and replicated to high titres (10(5) pfu/ml). Sequence analyses revealed
      that only one amino acid exchange in the H-protein at position 540 Asp->Gly
      (D540G) was required for functional adaptation to human CD150. Structural
      modelling suggests that the adaptive mutation D540G in H reflects the sequence
      alteration from canine to human CD150 at position 70 and 71 from Pro to Leu
      (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge
      in the human CD150 molecule. Using this model system our data indicate that only
      a minimal alteration, in this case one adaptive mutation, is required for
      adaptation of CDV to the human entry receptors, and help to understand the
      molecular basis why this adaptive mutation occurs.

PMID- 23554863
TI  - Liver fibrosis in type I Gaucher disease: magnetic resonance imaging, transient
      elastography and parameters of iron storage.
AB  - Long term liver-related complications of type-1 Gaucher disease (GD), a lysosomal
      storage disorder, include fibrosis and an increased incidence of hepatocellular
      carcinoma. Splenectomy has been implicated as a risk factor for the development
      of liver pathology in GD. High ferritin concentrations are a feature of GD and
      iron storage in Gaucher cells has been described, but iron storage in the liver
      in relation to liver fibrosis has not been studied. Alternatively, iron storage
      in GD may be the result of iron supplementation therapy or regular blood
      transfusions in patients with severe cytopenia. In this pilot study, comprising
      14 type-1 GD patients (7 splenectomized, 7 non-splenectomized) and 7 healthy
      controls, we demonstrate that liver stiffness values, measured by Transient
      Elastography and MR-Elastography, are significantly higher in splenectomized GD
      patients when compared with non-splenectomized GD patients (p = 0.03 and p =
      0.01, respectively). Liver iron concentration was elevated (>60+/-30 umol/g) in 4
      GD patients of whom 3 were splenectomized. No relationship was found between
      liver stiffness and liver iron concentration. HFE gene mutations were more
      frequent in splenectomized (6/7) than in non-splenectomized (2/7) participants (p
      = 0.10). Liver disease appeared more advanced in splenectomized than in non
      splenectomized patients. We hypothesize a relationship with excessive hepatic
      iron accumulation in splenectomized patients. We recommend that all
      splenectomized patients, especially those with evidence of substantial liver
      fibrosis undergo regular screening for HCC, according to current guidelines.

PMID- 23554864
TI  - Food insecurity, food based coping strategies and suboptimal dietary practices of
      adolescents in Jimma zone Southwest Ethiopia.
AB  - Despite the high prevalence of adolescent food insecurity in Ethiopia, there is
      no study which documented its association with suboptimal dietary practices. The
      objective of this study is to determine the association between adolescent food
      insecurity and dietary practices. We used data on 2084 adolescents in the age
      group of 13-17 years involved in the first round survey of the five year
      longitudinal family study in Southwest Ethiopia. Adolescents were selected using
      residence stratified random sampling methods. Food insecurity was measured using
      scales validated in developing countries. Dietary practices were measured using
      dietary diversity score, food variety score and frequency of consuming animal
      source food. Multivariable regression models were used to compare dietary
      behaviors by food security status after controlling for socio-demographic and
      economic covariates. Food insecure adolescents had low dietary diversity score
      (P<0.001), low mean food variety score (P<0.001) and low frequency of consuming
      animal source foods (P<0.001). After adjusting for other variables in a
      multivariable logistic regression model, adolescent food insecurity (P<0.001) and
      rural residence (P<0.001) were negatively associated with the likelihood of
      having a diversified diet (P<0.001) and frequency of consuming animal source
      foods, while a high household income tertile was positively associated.
      Similarly, multivariable linear regression model showed that adolescent food
      insecurity was negatively associated with food variety score, while residence in
      semi-urban areas (P<0.001), in urban areas (P<0.001) and high household income
      tertile (P = 0.013) were positively associated. Girls were less likely to have
      diversified diet (P = 0.001) compared with boys. Our findings suggest that food
      insecurity has negative consequence on optimal dietary intake of adolescents.
      Food security interventions should look into ways of targeting adolescents to
      mitigate these dietary consequences and provide alternative strategies to improve
      dietary quality of adolescents in Southwest Ethiopia.

PMID- 23554865
TI  - Structure and stability of human telomeric G-quadruplex with preclinical 9-amino
      acridines.
AB  - G-quadruplexes are higher-order DNA structures formed from guanine-rich
      sequences, and have been identified as attractive anticancer drug targets.
      Elucidating the three-dimensional structure of G-quadruplex with 9-amino
      acridines and the specific interactions involved in binding selectivity are the
      key to understanding their mechanism of action. Fluorescence titration assays,
      competitive dialysis and NMR studies have been used to study the binding
      specificity of 9-amino acridines to DNA. Structural models of the complexes with
      the telomeric DNA G-quadruplex based on NMR measurements were developed and
      further examined by molecular dynamics simulations and free energy calculations.
      Selective binding of 9-amino acridines for G-quadruplex sequences were observed.
      These compounds bind between A and G-tetrads, involving significant pi-pi
      interactions and several strong hydrogen bonds. The specific interactions between
      different moieties of the 9-amino acridines to the DNA were examined and shown to
      play a significant role in governing the overall stabilities of DNA G-quadruplex
      complexes. Both 9-amino acridines, with similar binding affinities to the G
      quadruplex, were shown to induce different level of structural stabilization
      through intercalation. This unique property of altering structural stability is
      likely a contributing factor for affecting telomerase function and, subsequently,
      the observed differences in the anticancer activities between the two 9-amino
      acridines.

PMID- 23554866
TI  - Identification of free nitric oxide radicals in rat bone marrow: implications for
      progenitor cell mobilization in hypertension.
AB  - Nitric oxide (NO) has been implicated in matrix metallopeptidase 9 (MMP9)
      dependent mobilization of hematopoietic stem and progenitor cells from bone
      marrow (BM). However, direct measurement of NO in the BM remained elusive due to
      its low in situ concentration and short lifetime. Using NO spin trapping and
      electron paramagnetic resonance (EPR) spectroscopy we give the first experimental
      confirmation of free NO radicals in rodent BM. NO production was quantified and
      attributed to enzymatic activity of NO synthases (NOS). Although endothelial NOS
      (eNOS) accounts for most (66%) of basal NO, we identified a significant
      contribution (23%) from inducible NOS (iNOS). Basal NO levels closely correlate
      with MMP9 bioavailability in BM of both hypertensive and control rats. Our
      observations support the hypothesis that inadequate mobilization of BM-derived
      stem and progenitor cells in hypertension results from impaired NOS/NO/MMP9
      signalling in BM, a condition that may be corrected with pharmacological
      intervention.

PMID- 23554867
TI  - Cost-effectiveness analysis of Option B+ for HIV prevention and treatment of
      mothers and children in Malawi.
AB  - BACKGROUND: The Ministry of Health in Malawi is implementing a pragmatic and
      innovative approach for the management of all HIV-infected pregnant women, termed
      Option B+, which consists of providing life-long antiretroviral treatment,
      regardless of their CD4 count or clinical stage. Our objective was to determine
      if Option B+ represents a cost-effective option. METHODS: A decision model
      simulates the disease progression of a cohort of HIV-infected pregnant women
      receiving prophylaxis and antiretroviral therapy, and estimates the number of
      paediatric infections averted and maternal life years gained over a ten-year time
      horizon. We assess the cost-effectiveness from the Ministry of Health perspective
      while taking into account the practical realities of implementing ART services in
      Malawi. RESULTS: If implemented as recommended by the World Health Organization,
      options A, B and B+ are equivalent in preventing new infant infections, yielding
      cost effectiveness ratios between US$ 37 and US$ 69 per disability adjusted life
      year averted in children. However, when the three options are compared to the
      current practice, the provision of antiretroviral therapy to all mothers (Option
      B+) not only prevents infant infections, but also improves the ten-year survival
      in mothers more than four-fold. This translates into saving more than 250,000
      maternal life years, as compared to mothers receiving only Option A or B, with
      savings of 153,000 and 172,000 life years respectively. Option B+ also yields
      favourable incremental cost effectiveness ratios (ICER) of US$ 455 per life year
      gained over the current practice. CONCLUSION: In Malawi, Option B+ represents a
      favorable policy option from a cost-effectiveness perspective to prevent future
      infant infections, save mothers' lives and reduce orphanhood. Although Option B+
      would require more financial resources initially, it would save societal
      resources in the long-term and represents a strategic option to simplify and
      integrate HIV services into maternal, newborn and child health programmes.

PMID- 23554868
TI  - Ex vivo modeling of chemical synergy in prenatal kidney cystogenesis.
AB  - Cyclic adenosine monophosphate (cAMP) drives genetic polycystic kidney disease
      (PKD) cystogenesis. Yet within certain PKD families, striking differences in
      disease severity exist between affected individuals, and genomic and/or
      environmental modifying factors have been evoked to explain these observations.
      We hypothesized that PKD cystogenesis is accentuated by an aberrant fetal milieu,
      specifically by glucocorticoids. The extent and nature of cystogenesis was
      assessed in explanted wild-type mouse embryonic metanephroi, using 8-Br-cAMP as a
      chemical to mimic genetic PKD and the glucocorticoid dexamethasone as the
      environmental modulator. Cysts and glomeruli were quantified by an observer
      blinded to culture conditions, and tubules were phenotyped using specific
      markers. Dexamethasone or 8-Br-cAMP applied on their own produced cysts
      predominantly arising in proximal tubules and descending limbs of loops of Henle.
      When applied together, however, dexamethasone over a wide concentration range
      synergized with 8-Br-cAMP to generate a more severe, glomerulocystic, phenotype;
      we note that prominent glomerular cysts have been reported in autosomal dominant
      PKD fetal kidneys. Our data support the idea that an adverse antenatal
      environment exacerbates renal cystogenesis.

PMID- 23554869
TI  - Perthamide C inhibits eNOS and iNOS expression and has immunomodulating activity
      in vivo.
AB  - Here we have characterized perthamide C, a cyclopeptide from a Solomon Lithistid
      sponge Theonella swinhoei, which displays an anti-inflammatory/immunomodulatory
      activity. The study has been performed using the carragenan-induced mouse paw
      edema that displays an early (0-6 h) and a late phase (24-96 h). Perthamide C
      significantly inhibits neutrophils infiltration in tissue both in the early and
      late phases. This effect was coupled to a reduced expression of the endothelial
      nitric oxide synthase (eNOS) in the early phase while cyclooxygenase-1 and 2 (COX
      1, COX-2), and inducible NOS (iNOS) expression were unaffected. In the late phase
      perthamide C reduced expression of both NOS isoforms without affecting COXs
      expression. This peculiar selectivity toward the two enzymes deputed to produce
      NO lead us to investigate on a possible action of perthamide C on lymphocytes
      infiltration and activation. We found that perthamide C inhibited the
      proliferation of peripheral lymphocytes, and that this effect was secondary to
      its metabolic activation in vivo. Indeed, in vitro perthamide C did not inhibit
      proliferation as opposite to its metabolite perthamide H. In conclusion,
      perthamide C selectively interferes with NO generation triggered by either eNOS
      or iNOS without affecting either COX-1 or COX-2. This in turn leads to modulation
      of the inflammatory response through a reduction of vascular permeability,
      neutrophil infiltration as well as lymphocyte proliferation.

PMID- 23554870
TI  - Mechano-chemical aspects of organ formation in Arabidopsis thaliana: the
      relationship between auxin and pectin.
AB  - How instructive signals are translated into robust and predictable changes in
      growth is a central question in developmental biology. Recently, much interest
      has centered on the feedback between chemical instructions and mechanical changes
      for pattern formation in development. In plants, the patterned arrangement of
      aerial organs, or phyllotaxis, is instructed by the phytohormone auxin; however,
      it still remains to be seen how auxin is linked, at the apex, to the biochemical
      and mechanical changes of the cell wall required for organ outgrowth. Here, using
      Atomic Force Microscopy, we demonstrate that auxin reduces tissue rigidity prior
      to organ outgrowth in the shoot apex of Arabidopsis thaliana, and that the de
      methyl-esterification of pectin is necessary for this reduction. We further show
      that development of functional organs produced by pectin-mediated ectopic wall
      softening requires auxin signaling. Lastly, we demonstrate that coordinated
      localization of the auxin transport protein, PIN1, is disrupted in a naked-apex
      produced by increasing cell wall rigidity. Our data indicates that a feedback
      loop between the instructive chemical auxin and cell wall mechanics may play a
      crucial role in phyllotactic patterning.

PMID- 23554871
TI  - Vitamin D receptor gene polymorphisms and prognosis of breast cancer among
      African-American and Hispanic women.
AB  - BACKGROUND: Vitamin D plays a role in cancer development and acts through the
      vitamin D receptor (VDR). Although African-Americans have the lowest levels of
      serum vitamin D, there is a dearth of information on VDR gene polymorphisms and
      breast cancer among African-Americans and Hispanics. This study examines whether
      VDR gene polymorphisms are associated with breast cancer in these cohorts.
      METHODS: Blood was collected from 232 breast cancer patients (Cases) and 349 non
      cancer subjects (Controls). Genotyping for four polymorphic variants of VDR
      (FokI, BsmI, TaqI and ApaI) was performed using the PCR-RFLP method. RESULTS: An
      increased association of the VDR-Fok1 f allele with breast cancer was observed in
      African-Americans (OR = 1.9, p = 0.07). Furthermore, the FbTA, FbtA and fbtA
      haplotypes were associated with breast cancer among African-Americans (p<0.05).
      Latinas were more likely to have the VDR-ApaI alleles (Aa or aa) (p = 0.008). The
      VDR-ApaI aa genotype was significantly associated with poorly-differentiated
      breast tumors (p = 0.04) in combined Cases. Kaplan-Meier survival analysis showed
      decreased 5-year disease-free-survival (DFS) in breast cancer patients who had
      the VDR-Fok1 FF genotype (p<0.05). The Cox regression with multivariate analysis
      revealed the independent predictor value of the VDR-FokI polymorphism for DFS.
      The other three variants of VDR (BsmI, TaqI and ApaI) were not associated with
      disease outcome. CONCLUSIONS: VDR haplotypes are associated with breast cancer in
      African-Americans, but not in Hispanic/Latinas. The VDR-FokI FF genotype is
      linked with poor prognosis in African-American women with breast cancer.

PMID- 23554872
TI  - Differential requirement for SUB1 in chromosomal and plasmid double-strand DNA
      break repair.
AB  - Non homologous end joining (NHEJ) is an important process that repairs double
      strand DNA breaks (DSBs) in eukaryotic cells. Cells defective in NHEJ are unable
      to join chromosomal breaks. Two different NHEJ assays are typically used to
      determine the efficiency of NHEJ. One requires NHEJ of linearized plasmid DNA
      transformed into the test organism; the other requires NHEJ of a single
      chromosomal break induced either by HO endonuclease or the I-SceI restriction
      enzyme. These two assays are generally considered equivalent and rely on the same
      set of NHEJ genes. PC4 is an abundant DNA binding protein that has been suggested
      to stimulate NHEJ. Here we tested the role of PC4's yeast homolog SUB1 in repair
      of DNA double strand breaks using different assays. We found SUB1 is required for
      NHEJ repair of DSBs in plasmid DNA, but not in chromosomal DNA. Our results
      suggest that these two assays, while similar are not equivalent and that repair
      of plasmid DNA requires additional factor(s) that are not required for NHEJ
      repair of chromosomal double-strand DNA breaks. Possible roles for Sub1 proteins
      in NHEJ of plasmid DNA are discussed.

PMID- 23554874
TI  - Photoluminescent gold nanoclusters as sensing probes for uropathogenic
      Escherichia coli.
AB  - Glycan-bound nanoprobes have been demonstrated as suitable sensing probes for
      bacteria containing glycan binding sites. In this study, we demonstrated a facile
      approach for generating glycan-bound gold nanoclusters (AuNCs). The generated
      AuNCs were used as sensing probes for corresponding target bacteria. Mannose
      capped AuNCs (AuNCs@Mann) were generated and used as the model sensors for target
      bacteria. A one-step synthesis approach was employed to generate AuNCs@Mann. In
      this approach, an aqueous solution of tetrachloroauric acid and mannoside that
      functionized with a thiol group (Mann-SH) was stirred at room temperature for 48
      h. The mannoside functions as reducing and capping agent. The size of the
      generated AuNCs@Mann is 1.95+/-0.27 nm, whereas the AuNCs with red
      photoluminescence have a maximum emission wavelength of ~630 nm (lambdaexcitation
      = 375 nm). The synthesis of the AuNCs@Mann was accelerated by microwave heating,
      which enabled the synthesis of the AuNCs@Mann to complete within 1 h. The
      generated AuNCs@Mann are capable of selectively binding to the urinary tract
      infection isolate Escherichia coli J96 containing the mannose binding protein
      FimH expressed on the type 1 pili. On the basis of the naked eye observation, the
      limit of detection of the sensing approach is as low as ~2*10(6) cells/mL.

PMID- 23554873
TI  - Rare genomic structural variants in complex disease: lessons from the replication
      of associations with obesity.
AB  - The limited ability of common variants to account for the genetic contribution to
      complex disease has prompted searches for rare variants of large effect, to
      partly explain the 'missing heritability'. Analyses of genome-wide genotyping
      data have identified genomic structural variants (GSVs) as a source of such rare
      causal variants. Recent studies have reported multiple GSV loci associated with
      risk of obesity. We attempted to replicate these associations by similar analysis
      of two familial-obesity case-control cohorts and a population cohort, and
      detected GSVs at 11 out of 18 loci, at frequencies similar to those previously
      reported. Based on their reported frequencies and effect sizes (OR>=25), we had
      sufficient statistical power to detect the large majority (80%) of genuine
      associations at these loci. However, only one obesity association was replicated.
      Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population
      frequency of 2*10(-4) (95% confidence interval [9.6*10(-5)-3.1*10(-4)]); accounts
      overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8*10(
      10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI)
      increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We
      also attempted replication using BMI as a quantitative trait in our population
      cohort; associations with BMI at or near nominal significance were detected at
      two further loci near KIF2B and within FOXP2, but these did not survive
      correction for multiple testing. These findings emphasise several issues of
      importance when conducting rare GSV association, including the need for careful
      cohort selection and replication strategy, accurate GSV identification, and
      appropriate correction for multiple testing and/or control of false discovery
      rate. Moreover, they highlight the potential difficulty in replicating rare CNV
      associations across different populations. Nevertheless, we show that such
      studies are potentially valuable for the identification of variants making an
      appreciable contribution to complex disease.

PMID- 23554875
TI  - Pulmonary tuberculosis incidence and risk factors in rural areas of China: a
      cohort study.
AB  - The incidence of tuberculosis (TB) and its risk factors in China remains unclear.
      This study examined TB incidence and relative risk factors in rural areas of
      China. Participants (n = 177,529) were recruited in Xiangtan County (in the
      central area of China) and in Danyang County (in the eastern area of China) in
      2009 and a followed-up study was conducted for one year. The incidence density of
      pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000
      person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in
      Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI:
      16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was
      associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in
      Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association
      between TB and per capita living space over median was found in Xiangtan, with
      the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the
      insurance status, the contact history with TB, the history of diabetes, smoking,
      or per capita annual income. The host genetic susceptibility, and social factors
      such as education and income could be considered in future studies.

PMID- 23554876
TI  - Response-locked brain dynamics of word production.
AB  - The cortical regions involved in the different stages of speech production are
      relatively well-established, but their spatio-temporal dynamics remain poorly
      understood. In particular, the available studies have characterized neural events
      with respect to the onset of the stimulus triggering a verbal response. The core
      aspect of language production, however, is not perception but action. In this
      context, the most relevant question may not be how long after a stimulus brain
      events happen, but rather how long before the production act do they occur. We
      investigated speech production-related brain activity time-locked to vocal onset,
      in addition to the common stimulus-locked approach. We report the detailed
      temporal interplay between medial and left frontal activities occurring shortly
      before vocal onset. We interpret those as reflections of, respectively, word
      selection and word production processes. This medial-lateral organization is in
      line with that described in non-linguistic action control, suggesting that
      similar processes are at play in word production and non-linguistic action
      production. This novel view of the brain dynamics underlying word production
      provides a useful background for future investigations of the spatio-temporal
      brain dynamics that lead to the production of verbal responses.

PMID- 23554877
TI  - Mesenchymal stem cells derived from adipose tissue vs bone marrow: in vitro
      comparison of their tropism towards gliomas.
AB  - INTRODUCTION: Glioblastoma is the most common primary malignant brain tumor, and
      is refractory to surgical resection, radiation, and chemotherapy. Human
      mesenchymal stem cells (hMSC) may be harvested from bone marrow (BMSC) and
      adipose (AMSC) tissue. These cells are a promising avenue of investigation for
      the delivery of adjuvant therapies. Despite extensive research into putative
      mechanisms for the tumor tropism of MSCs, there remains no direct comparison of
      the efficacy and specificity of AMSC and BMSC tropism towards glioma. METHODS:
      Under an IRB-approved protocol, intraoperative human Adipose MSCs (hAMSCs) were
      established and characterized for cell surface markers of mesenchymal stem cell
      origin in conjunction with the potential for tri-lineage differentiation
      (adipogenic, chondrogenic, and osteogenic). Validated experimental hAMSCs were
      compared to commercially derived hBMSCs (Lonza) and hAMSCs (Invitrogen) for
      growth responsiveness and glioma tropism in response to glioma conditioned media
      obtained from primary glioma neurosphere cultures. RESULTS: Commercial and
      primary culture AMSCs and commercial BMSCs demonstrated no statistically
      significant difference in their migration towards glioma conditioned media in
      vitro. There was statistically significant difference in the proliferation rate
      of both commercial AMSCs and BMSCs as compared to primary culture AMSCs,
      suggesting primary cultures have a slower growth rate than commercially available
      cell lines. CONCLUSIONS: Adipose- and bone marrow-derived mesenchymal stem cells
      have similar in vitro glioma tropism. Given the well-documented ability to
      harvest larger numbers of AMSCs under local anesthesia, adipose tissue may
      provide a more efficient source of MSCs for research and clinical applications,
      while minimizing patient morbidity during cell harvesting.

PMID- 23554878
TI  - Identification of ovarian cancer metastatic miRNAs.
AB  - Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive
      metastatic disease, yet little is known about the behavior and genetics of
      ovarian cancer metastasis. Here, we aim to understand how omental metastases
      differ from primary tumors and how these differences may influence chemotherapy.
      We analyzed the miRNA expression profiles of primary EOC tumors and their
      respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We
      find 17 miRNAs with differential expression in omental lesions compared to
      primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary
      tumors with significantly increased expression in omental lesions, with
      concomitant decreased expression of predicted mRNA targets based on mRNA
      expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR
      146a and miR-150 increase the number of residual surviving cells by 2-4 fold when
      challenged with lethal cisplatin concentrations. These observations suggest that
      at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental
      lesions, stimulate survival and increase drug tolerance. Our observations suggest
      that cancer cells in omental tumors express key miRNAs differently than primary
      tumors, and that at least some of these microRNAs may be critical regulators of
      the emergence of drug resistant disease.

PMID- 23554879
TI  - PINCH in the cellular stress response to tau-hyperphosphorylation.
AB  - Particularly interesting new cysteine- histidine- rich protein (PINCH) is an
      adaptor protein that our data have shown is required for neurite extension under
      stressful conditions. Our previous studies also report that PINCH is recalled by
      neurons showing decreased levels of synaptodendritic signaling proteins such as
      MAP2 or synaptophysin in the brains of human immunodeficiency virus (HIV)
      patients. The current study addressed potential role(s) for PINCH in
      neurodegenerative diseases. Mass spectrometry predicted the interaction of PINCH
      with Tau and with members of the heat shock response. Our in vitro data confirmed
      that PINCH binds to hyperphosphorylated (hp) Tau and to E3 ubiquitin ligase,
      carboxy-terminus of heat shock-70 interacting protein. Silencing PINCH prior to
      induction of hp-Tau resulted in more efficient clearance of accumulating hp-Tau,
      suggesting that PINCH may play a role in stabilizing hp-Tau. Accumulation of hp
      Tau is implicated in more than 20 neuropathological diseases including
      Alzheimer's disease (AD), frontotemporal dementia (FTD), and human
      immunodeficiency virus encephalitis (HIVE). Analyses of brain tissues from HIVE,
      AD and FTD patients showed that PINCH is increased and binds to hp-Tau. These
      studies address a new mechanism by which AD and HIV may intersect and identify
      PINCH as a contributing factor to the accumulation of hyperphosphorylated Tau.

PMID- 23554880
TI  - Genetic predisposition to pass the standard SICCT test for bovine tuberculosis in
      British cattle.
AB  - Bovine tuberculosis (bTB) imposes an important financial burden on the British
      cattle industry, yet despite intense efforts to control its spread, incidence is
      currently rising. Surveillance for bTB is based on a skin test that measures an
      immunological response to tuberculin. Cattle that fail the test are classified as
      "reactors" and slaughtered. Recent studies have identified genetic markers
      associated with the reaction of cattle to the tuberculin test. At marker INRA111
      a relatively common '22' genotype occurs significantly more frequently in non
      reactor cattle. Here we test the possibility that the putative protective '22'
      genotype does not confer resistance but instead causes cattle that carry it to
      react less strongly to the prescribed test, and hence avoid slaughter,
      potentially even though they are infected. We show that, after controlling for
      age and breed, '22' cattle react less strongly to the immunological challenge and
      may therefore be less likely to be classified as a reactor. These results
      highlight the potential discrepancy between infection and test status and imply
      that the effectiveness of the test-and-slaughter policy may be being compromised
      by selection for cattle that are genetically predisposed to react less strongly
      to tuberculin.

PMID- 23554881
TI  - CovR and VicRK regulate cell surface biogenesis genes required for biofilm
      formation in Streptococcus mutans.
AB  - The two-component system VicRK and the orphan regulator CovR of Streptococcus
      mutans co-regulate a group of virulence genes associated with the synthesis of
      and interaction with extracellular polysaccharides of the biofilm matrix.
      Knockout mutants of vicK and covR display abnormal cell division and morphology
      phenotypes, although the gene function defects involved are as yet unknown. Using
      transcriptomic comparisons between parent strain UA159 with vicK (UAvic) or covR
      (UAcov) deletion mutants together with electrophoretic motility shift assays
      (EMSA), we identified genes directly regulated by both VicR and CovR with
      putative functions in cell wall/surface biogenesis, including gbpB, wapE, smaA,
      SMU.2146c, and lysM. Deletion mutants of genes regulated by VicR and CovR (wapE,
      lysM, smaA), or regulated only by VicR (SMU.2146c) or CovR (epsC) promoted
      significant alterations in biofilm initiation, including increased fragility,
      defects in microcolony formation, and atypical cell morphology and/or chaining.
      Significant reductions in mureinolytic activity and/or increases in DNA release
      during growth were observed in knockout mutants of smaA, wapE, lysM, SMU.2146c
      and epsC, implying roles in cell wall biogenesis. WapE and lysM mutations also
      affected cell hydrophobicity and sensitivity to osmotic or oxidative stress.
      Finally, vicR, covR and VicRK/CovR-targets (gbpB, wapE, smaA, SMU.2146c, lysM,
      epsC) are up-regulated in UA159 during biofilm initiation, in a sucrose-dependent
      manner. These data support a model in which VicRK and CovR coordinate cell
      division and surface biogenesis with the extracellular synthesis of
      polysaccharides, a process apparently required for formation of structurally
      stable biofilms in the presence of sucrose.

PMID- 23554882
TI  - Translating resuscitation guidelines into practice: health care provider
      attitudes, preferences and beliefs regarding pediatric fluid resuscitation
      performance.
AB  - INTRODUCTION: Children who require fluid resuscitation for the treatment of shock
      present to tertiary and non-tertiary medical settings. While timely fluid therapy
      improves survival odds, guidelines are poorly translated into clinical practice.
      The objective of this study was to characterize the attitudes, preferences and
      beliefs of health care providers working in acute care settings regarding
      pediatric fluid resuscitation performance. METHODS: A single-centre survey study
      was conducted at McMaster Children's Hospital from January to May, 2012. The
      sampling frame (n = 115) included nursing staff, physician staff and subspecialty
      trainees working in Pediatric Emergency Medicine (PEM) or Pediatric Critical Care
      Medicine (PCCM). A self-administered questionnaire was developed and assessed for
      face validity prior to distribution. Eligible participants were invited at 0, 2,
      and 4 weeks to complete a web-based version of the survey. A follow-up survey
      administration phase was conducted to improve the response rate. RESULTS:
      Response rate was 72.2% (83/115), with 83% (68/82) self-identifying as nursing
      staff and 61% (50/82) as PCCM providers. Resuscitation experience, frequency of
      shock management, and years in specialty, were similar between PCCM and PEM
      responders. Physicians and nurses had differing opinions regarding the most
      effective method to achieve rapid fluid resuscitation in young children
      presenting in shock (p<0.001). Disagreement also existed regarding the age and
      size of patients in whom rapid infuser devices, such as the Level-1 Rapid
      Infuser, should be used (p<0.001). Providers endorsed a number of potential
      concerns related to the use of rapid infuser devices in children, and only 14% of
      physicians and 55% of nursing staff felt that they had received adequate training
      in the use of such devices (p = 0.005). CONCLUSIONS: There is a lack of consensus
      among health care providers regarding how pediatric fluid resuscitation
      guidelines should be operationalized, supporting a need for further work to
      define best practices.

PMID- 23554884
TI  - Calcium induced regulation of skeletal troponin--computational insights from
      molecular dynamics simulations.
AB  - The interaction between calcium and the regulatory site(s) of striated muscle
      regulatory protein troponin switches on and off muscle contraction. In skeletal
      troponin binding of calcium to sites I and II of the TnC subunit results in a set
      of structural changes in the troponin complex, displaces tropomyosin along the
      actin filament and allows myosin-actin interaction to produce mechanical force.
      In this study, we used molecular dynamics simulations to characterize the calcium
      dependent dynamics of the fast skeletal troponin molecule and its TnC subunit in
      the calcium saturated and depleted states. We focused on the N-lobe and on
      describing the atomic level events that take place subsequent to removal of the
      calcium ion from the regulatory sites I and II. A main structural event - a
      closure of the A/B helix hydrophobic pocket results from the integrated effect of
      the following conformational changes: the breakage of H-bond interactions between
      the backbone nitrogen atoms of the residues at positions 2, 9 and sidechain
      oxygen atoms of the residue at position 12 (N(2)-OE(12)/N(9)-OE(12)) in sites I
      and II; expansion of sites I and II and increased site II N-terminal end-segment
      flexibility; strengthening of the beta-sheet scaffold; and the subsequent re
      packing of the N-lobe hydrophobic residues. Additionally, the calcium release
      allows the N-lobe to rotate relative to the rest of the Tn molecule. Based on the
      findings presented herein we propose a novel model of skeletal thin filament
      regulation.

PMID- 23554883
TI  - Attractor metabolic networks.
AB  - BACKGROUND: The experimental observations and numerical studies with dissipative
      metabolic networks have shown that cellular enzymatic activity self-organizes
      spontaneously leading to the emergence of a Systemic Metabolic Structure in the
      cell, characterized by a set of different enzymatic reactions always locked into
      active states (metabolic core) while the rest of the catalytic processes are only
      intermittently active. This global metabolic structure was verified for
      Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems
      to be a common key feature to all cellular organisms. In concordance with these
      observations, the cell can be considered a complex metabolic network which mainly
      integrates a large ensemble of self-organized multienzymatic complexes
      interconnected by substrate fluxes and regulatory signals, where multiple
      autonomous oscillatory and quasi-stationary catalytic patterns simultaneously
      emerge. The network adjusts the internal metabolic activities to the external
      change by means of flux plasticity and structural plasticity.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to research the systemic mechanisms
      involved in the regulation of the cellular enzymatic activity we have studied
      different catalytic activities of a dissipative metabolic network under different
      external stimuli. The emergent biochemical data have been analysed using
      statistical mechanic tools, studying some macroscopic properties such as the
      global information and the energy of the system. We have also obtained an
      equivalent Hopfield network using a Boltzmann machine. Our main result shows that
      the dissipative metabolic network can behave as an attractor metabolic network.
      CONCLUSIONS/SIGNIFICANCE: We have found that the systemic enzymatic activities
      are governed by attractors with capacity to store functional metabolic patterns
      which can be correctly recovered from specific input stimuli. The network
      attractors regulate the catalytic patterns, modify the efficiency in the
      connection between the multienzymatic complexes, and stably retain these
      modifications. Here for the first time, we have introduced the general concept of
      attractor metabolic network, in which this dynamic behavior is observed.

PMID- 23554885
TI  - 5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent
      angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo.
AB  - BACKGROUND: Insufficient angiogenesis and arteriogenesis in cardiac tissue after
      myocardial infarction (MI) is a significant factor hampering the functional
      recovery of the heart. To overcome this problem we screened for compounds capable
      of stimulating angiogenesis, and herein investigate the most active molecule, 5
      Methoxyleoligin (5ML), in detail. METHODS AND RESULTS: 5ML potently stimulated
      endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken
      chorioallantoic membrane assay. Further, microarray- and knock down- based
      analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an
      in vivo rat MI model 5ML potently increased the number of arterioles in the peri
      infarction and infarction area, reduced myocardial muscle loss, and led to a
      significant increase in LV function (plus 21% 28 days after MI). CONCLUSION: The
      present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and
      arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo
      arteriogenesis is not clear at the moment. Importantly, 5ML-induced
      arteriogenesis in vivo makes the compound even more interesting for a post MI
      therapy. 5ML may constitute the first low molecular weight compound leading to an
      improvement of myocardial function after MI.

PMID- 23554886
TI  - N, N'-Olefin functionalized bis-imidazolium gold(I) salt is an efficient
      candidate to control keratitis-associated eye infection.
AB  - Keratitis treatment has become more complicated due to the emergence of bacterial
      or fungal pathogens with enhanced antibiotic resistance. The pharmaceutical
      applications of N-heterocyclic carbene complexes have received remarkable
      attention due to their antimicrobial properties. In this paper, the new
      precursor, 3,3'-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium}
      bromide (1a) and its analogous PF6 salt (1b) were synthesized. Furthermore,
      silver(I) and gold(I) -N-heterocyclic carbene (NHC) complexes [Ag2LBr2/Au2LBr2;
      2a/3a], [(Ag2L2)(PF6)2/(Au2L2)(PF6)2; 2b/3b] were developed from their
      corresponding ligands. All compounds were screened for their antimicrobial
      activities against multiple keratitis-associated human eye pathogens, including
      bacteria and fungi. Complexes 2a and 3a showed highest activity, and the
      effectiveness of 3a was also studied, focusing eradication of pathogen biofilm.
      Furthermore, the structures of 1a, 2a and 3b were determined using single crystal
      X-ray analysis, 2b and 3a were optimized theoretically. The mechanism of action
      of 3a was evaluated by scanning electron microscopy and docking experiments,
      suggesting that its target is the cell membrane. In summary, 3a may be helpful in
      developing antimicrobial therapies in patients suffering from keratitis
      associated eye infections caused by multidrug-resistant pathogens.

PMID- 23554887
TI  - Anti-analgesic effect of the mu/delta opioid receptor heteromer revealed by
      ligand-biased antagonism.
AB  - Delta (DOR) and mu opioid receptors (MOR) can complex as heteromers, conferring
      functional properties in agonist binding, signaling and trafficking that can
      differ markedly from their homomeric counterparts. Because of these differences,
      DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain.
      However, there are currently no ligands selective for DOR/MOR heteromers, and,
      consequently, their role in nociception remains unknown. In this study, we used a
      pharmacological opioid cocktail that selectively activates and stabilizes the
      DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its
      role in antinociception. We found that mice treated chronically with this drug
      cocktail showed a significant right shift in the ED50 for opioid-mediated
      analgesia, while mice treated with a drug that promotes degradation of the
      heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer
      after the right shift in the ED50 had occurred, or blocking signal transduction
      from the stabilized DOR/MOR heteromer, shifted the ED50 for analgesia back to the
      left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR
      heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer
      could provide an avenue for alleviating reduced analgesic response during chronic
      pain treatment.

PMID- 23554888
TI  - Effectiveness of percutaneous coronary intervention within 12 hours to 28 days of
      ST-elevation myocardial infarction in a real-world Chinese population.
AB  - OBJECTIVES: Percutaneous coronary intervention( PCI) for ST-elevation myocardial
      infarction (STEMI) has been widely accepted for patient who come within 12 hours,
      but for those who come to the hospital late (12 hours to 28 days) the long-term
      data and possible predictors are limited regarding 'hard' endpoints in 'real
      world'. METHODS: The registry data of all 5523 consecutive patients admitted due
      to an incident STEMI (12 hours to 28 days) in our center were analyzed. Patients
      were divided into 3 age groups (age<65; age = 65-74; age >=75) and two
      therapeutic groups including conservative and PCI group. The primary endpoints
      included 30-day mortality and 1-year mortality. RESULTS: The clinical
      characteristics include female gender; history of diabetes mellitus, previous
      myocardial infarction, cerebral vascular disease, chronic renal failure, atrial
      fibrillation, hypertension, anemia, gastric bleeding; presentation of ventricular
      tachycardia/ventricular fibrillation, pneumonia, heart failure, multiple organ
      failure and cardiogenic shock. The ratio of all the above factors increased with
      the age getting older (all p<0.05), while that of the PCI decreased significantly
      with ageing (53.9%, 36.3% and 21.7%). Except hypertension, all the other factors
      were less seen in the PCI group than in the conservative group (p<0.01). Pooled
      estimates, based on type of therapy and age groups, PCI resulted in significantly
      lower 30-day and 1-year mortality. Cox analysis showed the positive predictors
      for 30 days and 1 year mortality were heart failure, cerebral vascular disease,
      chronic renal failure, ventricular tachycardia/ventricular fibrillation, age,
      female, gastric intestinal bleeding, cardiogenic shock, multiple organ failure,
      while PCI was a negative predictor. ROCs analysis showed AUCs were always higher
      for PCI group. CONCLUSIONS: The elderly have more comorbidities and higher rates
      of mortality, mandating thorough evaluation before acceptance for PCI. PCI
      between 12 hours to 28 days in all ages of patients including the elderly with
      STEMI is significantly more effective than conservative therapy.

PMID- 23554889
TI  - Celastrol suppresses tumor cell growth through targeting an AR-ERG-NF-kappaB
      pathway in TMPRSS2/ERG fusion gene expressing prostate cancer.
AB  - The TMPRSS2/ERG (T/E) fusion gene is present in the majority of all prostate
      cancers (PCa). We have shown previously that NF-kB signaling is highly activated
      in these T/E fusion expressing cells via phosphorylation of NF-kB p65 Ser536
      (p536). We therefore hypothesize that targeting NF-kB signaling may be an
      efficacious approach for the subgroup of PCas that carry T/E fusions. Celastrol
      is a well known NF-kB inhibitor, and thus may inhibit T/E fusion expressing PCa
      cell growth. We therefore evaluated Celastrol's effects in vitro and in vivo in
      VCaP cells, which express the T/E fusion gene. VCaP cells were treated with
      different concentrations of Celastrol and growth inhibition and target expression
      were evaluated. To test its ability to inhibit growth in vivo, 0.5 mg/kg
      Celastrol was used to treat mice bearing subcutaneous VCaP xenograft tumors. Our
      results show Celastrol can significantly inhibit the growth of T/E fusion
      expressing PCa cells both in vitro and in vivo through targeting three critical
      signaling pathways: AR, ERG and NF-kB in these cells. When mice received 0.5
      mg/kg Celastrol for 4 times/week, significant growth inhibition was seen with no
      obvious toxicity or significant weight loss. Therefore, Celastrol is a promising
      candidate drug for T/E fusion expressing PCa. Our findings provide a novel
      strategy for the targeted therapy which may benefit the more than half of PCa
      patients who have T/E fusion expressing PCas.

PMID- 23554890
TI  - Oral probiotic microcapsule formulation ameliorates non-alcoholic fatty liver
      disease in Bio F1B Golden Syrian hamsters.
AB  - The beneficial effect of a microencapsulated feruloyl esterase producing
      Lactobacillus fermentum ATCC 11976 formulation for use in non-alcoholic fatty
      liver disease (NAFLD) was investigated. For which Bio F1B Golden Syrian hamsters
      were fed a methionine deficient/choline devoid diet to induce non-alcoholic fatty
      liver disease. Results, for the first time, show significant clinical benefits in
      experimental animals. Examination of lipids show that concentrations of hepatic
      free cholesterol, esterified cholesterol, triglycerides and phospholipids were
      significantly lowered in treated animals. In addition, serum total cholesterol,
      triglycerides, uric acid and insulin resistance were found to decrease in treated
      animals. Liver histology evaluations showed reduced fat deposits. Western blot
      analysis shows significant differences in expression levels of key liver enzymes
      in treated animals. In conclusion, these findings suggest the excellent potential
      of using an oral probiotic formulation to ameliorate NAFLD.

PMID- 23554891
TI  - Experimental and natural warming elevates mercury concentrations in estuarine
      fish.
AB  - Marine food webs are the most important link between the global contaminant,
      methylmercury (MeHg), and human exposure through consumption of seafood. Warming
      temperatures may increase human exposure to MeHg, a potent neurotoxin, by
      increasing MeHg production as well as bioaccumulation and trophic transfer
      through marine food webs. Studies of the effects of temperature on MeHg
      bioaccumulation are rare and no study has specifically related temperature to
      MeHg fate by linking laboratory experiments with natural field manipulations in
      coastal ecosystems. We performed laboratory and field experiments on MeHg
      accumulation under varying temperature regimes using the killifish, Fundulus
      heteroclitus. Temperature treatments were established in salt pools on a coastal
      salt marsh using a natural temperature gradient where killifish fed on natural
      food sources. Temperatures were manipulated across a wider range in laboratory
      experiments with killifish exposed to MeHg enriched food. In both laboratory
      microcosms and field mesocosms, MeHg concentrations in killifish significantly
      increased at elevated temperatures. Moreover, in field experiments, other
      ancillary variables (salinity, MeHg in sediment, etc.) did not relate to MeHg
      bioaccumulation. Modeling of laboratory experimental results suggested increases
      in metabolic rate as a driving factor. The elevated temperatures we tested are
      consistent with predicted trends in climate warming, and indicate that in the
      absence of confounding factors, warmer sea surface temperatures could result in
      greater in bioaccumulation of MeHg in fish, and consequently, increased human
      exposure.

PMID- 23554892
TI  - Identification of a novel human papillomavirus by metagenomic analysis of samples
      from patients with febrile respiratory illness.
AB  - As part of a virus discovery investigation using a metagenomic approach, a highly
      divergent novel Human papillomavirus type was identified in pooled convenience
      nasal/oropharyngeal swab samples collected from patients with febrile respiratory
      illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that
      the new HPV identified in this study clusters with previously described gamma
      papillomaviruses, sharing only 61.1% (whole genome) and 63.1% (L1) sequence
      identity with its closest relative in the Papillomavirus episteme (PAVE)
      database. This new virus was named HPV_SD2 pending official classification. The
      complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C) and contains 7 open
      reading frames (L2, L1, E6, E7, E1, E2 and E4) and a non-coding long control
      region (LCR) between L1 and E6. The metagenomic procedures, coupled with the
      bioinformatic methods described herein are well suited to detect small circular
      genomes such as those of human papillomaviruses.

PMID- 23554893
TI  - MicroRNA profiling in human neutrophils during bone marrow granulopoiesis and in
      vivo exudation.
AB  - The purpose of this study was to describe the microRNA (miRNA) expression
      profiles of neutrophils and their precursors from the initiation of
      granulopoiesis in the bone marrow to extravasation and accumulation in skin
      windows. We analyzed three different cell populations from human bone marrow,
      polymorphonuclear neutrophil (PMNs) from peripheral blood, and extravasated PMNs
      from skin windows using the Affymetrix 2.0 platform. Our data reveal 135 miRNAs
      differentially regulated during bone marrow granulopoiesis. The majority is
      differentially regulated between the myeloblast/promyelocyte (MB/PM) and
      myelocyte/metamyelocyte (MC/MM) stages of development. These 135 miRNAs were
      divided into six clusters according to the pattern of their expression. Several
      miRNAs demonstrate a pronounced increase or reduction at the transition between
      MB/PM and MC/MM, which is associated with cell cycle arrest and the initiation of
      terminal differentiation. Seven miRNAs are differentially up-regulated between
      peripheral blood PMNs and extravasated PMNs and only one of these (miR-132) is
      also differentially regulated during granulopoiesis. The study indicates that
      several different miRNAs participate in the regulation of normal granulopoiesis
      and that miRNAs might also regulate activities of extravasated neutrophils. The
      data present the miRNA profiles during the development and activation of the
      neutrophil granulocyte in healthy humans and thus serves as a reference for
      further research of normal and malignant granulocytic development.

PMID- 23554894
TI  - Drawing from memory: hand-eye coordination at multiple scales.
AB  - Eyes move to gather visual information for the purpose of guiding behavior. This
      guidance takes the form of perceptual-motor interactions on short timescales for
      behaviors like locomotion and hand-eye coordination. More complex behaviors
      require perceptual-motor interactions on longer timescales mediated by memory,
      such as navigation, or designing and building artifacts. In the present study,
      the task of sketching images of natural scenes from memory was used to examine
      and compare perceptual-motor interactions on shorter and longer timescales. Eye
      and pen trajectories were found to be coordinated in time on shorter timescales
      during drawing, and also on longer timescales spanning study and drawing periods.
      The latter type of coordination was found by developing a purely spatial analysis
      that yielded measures of similarity between images, eye trajectories, and pen
      trajectories. These results challenge the notion that coordination only unfolds
      on short timescales. Rather, the task of drawing from memory evokes perceptual
      motor encodings of visual images that preserve coarse-grained spatial information
      over relatively long timescales as well.

PMID- 23554895
TI  - Additional routes to Staphylococcus aureus daptomycin resistance as revealed by
      comparative genome sequencing, transcriptional profiling, and phenotypic studies.
AB  - Daptomycin is an extensively used anti-staphylococcal agent due to the rise in
      methicillin-resistant Staphylococcus aureus, but the mechanism(s) of resistance
      is poorly understood. Comparative genome sequencing, transcriptomics,
      ultrastructure, and cell envelope studies were carried out on two relatively
      higher level (4 and 8 ug/ml(-1)) laboratory-derived daptomycin-resistant strains
      (strains CB1541 and CB1540 respectively) compared to their parent strain (CB1118;
      MW2). Several mutations were found in the strains. Both strains had the same
      mutations in the two-component system genes walK and agrA. In strain CB1540
      mutations were also detected in the ribose phosphate pyrophosphokinase (prs) and
      polyribonucleotide nucleotidyltransferase genes (pnpA), a hypothetical protein
      gene, and in an intergenic region. In strain CB1541 there were mutations in clpP,
      an ATP-dependent protease, and two different hypothetical protein genes. The
      strain CB1540 transcriptome was characterized by upregulation of cap (capsule)
      operon genes, genes involved in the accumulation of the compatible solute glycine
      betaine, ure genes of the urease operon, and mscL encoding a mechanosensitive
      chanel. Downregulated genes included smpB, femAB and femH involved in the
      formation of the pentaglycine interpeptide bridge, genes involved in protein
      synthesis and fermentation, and spa encoding protein A. Genes altered in their
      expression common to both transcriptomes included some involved in glycine
      betaine accumulation, mscL, ure genes, femH, spa and smpB. However, the CB1541
      transcriptome was further characterized by upregulation of various heat shock
      chaperone and protease genes, consistent with a mutation in clpP, and lytM and
      sceD. Both strains showed slow growth, and strongly decreased autolytic activity
      that appeared to be mainly due to decreased autolysin production. In contrast to
      previous common findings, we did not find any mutations in phospholipid
      biosynthesis genes, and it appears there are multiple pathways to and factors in
      daptomycin resistance.

PMID- 23554896
TI  - Tetra- and penta-acylated lipid A structures of Porphyromonas gingivalis LPS
      differentially activate TLR4-mediated NF-kappaB signal transduction cascade and
      immuno-inflammatory response in human gingival fibroblasts.
AB  - BACKGROUND: Porphyromonas gingivalis is a major pathogen of periodontal disease
      that affects a majority of adults worldwide. Increasing evidence shows that
      periodontal disease is linked to various systemic diseases like diabetes and
      cardiovascular disease, by contributing to increased systemic levels of
      inflammation. Lipopolysaccharides (LPS), as a key virulent attribute of P.
      gingivalis, possesses significant amount of lipid A heterogeneity containing
      tetra- (LPS1435/1449) and penta-acylated (LPS1690) structures. Hitherto, the
      exact molecular mechanism of P. gingivalis LPS involved in periodontal
      pathogenesis remains unclear, due to limited understanding of the specific
      receptors and signaling pathways involved in LPS-host cell interactions.
      METHODOLOGY/PRINCIPAL FINDINGS: This study systematically investigated the
      effects of P. gingivalis LPS1435/1449 and LPS1690 on the expression of TLR2 and
      TLR4 signal transduction and the activation of pro-inflammatory cytokines IL-6
      and IL-8 in human gingival fibroblasts (HGFs). We found that LPS1435/1449 and
      LPS1690 differentially modulated TLR2 and TLR4 expression. NF-kappaB pathway was
      significantly activated by LPS1690 but not by LPS1435/1449. In addition, LPS1690
      induced significant expression of NF-kappaB and p38 MPAK pathways-related genes,
      such as NFKBIA, NFKB1, IKBKB, MAP2K4 and MAPK8. Notably, the pro-inflammatory
      genes including GM-CSF, CXCL10, G-CSF, IL-6, IL-8 and CCL2 were significantly
      upregulated by LPS1690 while down-regulated by LPS1435/1449. Blocking assays
      confirmed that TLR4-mediated NF-kappaB signaling was vital in LPS1690-induced
      expression of IL-6 and IL-8 in HGFs. CONCLUSIONS/SIGNIFICANCE: The present study
      suggests that the tetra- and penta-acylated lipid A structures of P. gingivalis
      LPS differentially activate TLR4-mediated NF-kappaB signaling pathway, and
      significantly modulate the expression of IL-6 and IL-8 in HGFs. The ability to
      alter the lipid A structure of LPS could be one of the strategies carried-out by
      P. gingivalis to evade innate host defense in gingival tissues, thereby
      contributing to periodontal pathogenesis.

PMID- 23554897
TI  - Discordant results obtained with Francisella tularensis during in vitro and in
      vivo immunological studies are attributable to compromised bacterial structural
      integrity.
AB  - Francisella tularensis (Ft) is a highly infectious intracellular pathogen and the
      causative agent of tularemia. Because Ft can be dispersed via small droplet
      aerosols and has a very low infectious dose it is characterized as a category A
      Select Agent of biological warfare. Respiratory infection with the attenuated
      Live Vaccine Strain (LVS) and the highly virulent SchuS4 strain of Ft engenders
      intense peribronchiolar and perivascular inflammation, but fails to elicit select
      pro-inflammatory mediators (e.g., TNF, IL-1beta, IL-6, IL-12, and IFN-gamma)
      within the first ~72 h. This in vivo finding is discordant with the principally
      TH1-oriented response to Ft frequently observed in cell-based studies wherein the
      aforementioned cytokines are produced. An often overlooked confounding factor in
      the interpretation of experimental results is the influence of environmental cues
      on the bacterium's capacity to elicit certain host responses. Herein, we reveal
      that adaptation of Ft to its mammalian host imparts an inability to elicit select
      pro-inflammatory mediators throughout the course of infection. Furthermore, in
      vitro findings that non-host adapted Ft elicits such a response from host cells
      reflect aberrant recognition of the DNA of structurally-compromised bacteria by
      AIM2-dependent and -independent host cell cytosolic DNA sensors. Growth of Ft in
      Muller-Hinton Broth or on Muller-Hinton-based chocolate agar plates or genetic
      mutation of Ft was found to compromise the structural integrity of the bacterium
      thus rendering it capable of aberrantly eliciting pro-inflammatory mediators
      (e.g., TNF, IL-1beta, IL-6, IL-12, and IFN-gamma). Our studies highlight the
      profound impact of different growth conditions on host cell response to infection
      and demonstrate that not all in vitro-derived findings may be relevant to
      tularemia pathogenesis in the mammalian host. Rational development of a vaccine
      and immunotherapeutics can only proceed from a foundation of knowledge based upon
      in vitro findings that recapitulate those observed during natural infection.

PMID- 23554898
TI  - Patterns of Limnohabitans microdiversity across a large set of freshwater
      habitats as revealed by Reverse Line Blot Hybridization.
AB  - Among abundant freshwater Betaproteobacteria, only few groups are considered to
      be of central ecological importance. One of them is the well-studied genus
      Limnohabitans and mainly its R-BT subcluster, investigated previously mainly by
      fluorescence in situ hybridization methods. We designed, based on sequences from
      a large Limnohabitans culture collection, 18 RLBH (Reverse Line Blot
      Hybridization) probes specific for different groups within the genus
      Limnohabitans by targeting diagnostic sequences on their 16 S-23 S rRNA ITS
      regions. The developed probes covered in sum 92% of the available isolates. This
      set of probes was applied to environmental DNA originating from 161 different
      European standing freshwater habitats to reveal the microdiversity (intra-genus)
      patterns of the Limnohabitans genus along a pH gradient. Investigated habitats
      differed in various physicochemical parameters, and represented a very broad
      range of standing freshwater habitats. The Limnohabitans microdiversity, assessed
      as number of RLBH-defined groups detected, increased significantly along the
      gradient of rising pH of habitats. 14 out of 18 probes returned detection signals
      that allowed predictions on the distribution of distinct Limnohabitans groups.
      Most probe-defined Limnohabitans groups showed preferences for alkaline habitats,
      one for acidic, and some seemed to lack preferences. Complete niche-separation
      was indicated for some of the probe-targeted groups. Moreover, bimodal
      distributions observed for some groups of Limnohabitans, suggested further niche
      separation between genotypes within the same probe-defined group. Statistical
      analyses suggested that different environmental parameters such as pH,
      conductivity, oxygen and altitude influenced the distribution of distinct groups.
      The results of our study do not support the hypothesis that the wide ecological
      distribution of Limnohabitans bacteria in standing freshwater habitats results
      from generalist adaptations of these bacteria. Instead, our observations suggest
      that the genus Limnohabitans, as well as its R-BT subgroup, represent
      ecologically heterogeneous taxa, which underwent pronounced ecological
      diversification.

PMID- 23554899
TI  - DendroBLAST: approximate phylogenetic trees in the absence of multiple sequence
      alignments.
AB  - The rapidly growing availability of genome information has created considerable
      demand for both fast and accurate phylogenetic inference algorithms. We present a
      novel method called DendroBLAST for reconstructing phylogenetic dendrograms/trees
      from protein sequences using BLAST. This method differs from other methods by
      incorporating a simple model of sequence evolution to test the effect of
      introducing sequence changes on the reliability of the bipartitions in the
      inferred tree. Using realistic simulated sequence data we demonstrate that this
      method produces phylogenetic trees that are more accurate than other commonly
      used distance based methods though not as accurate as maximum likelihood methods
      from good quality multiple sequence alignments. In addition to tests on simulated
      data, we use DendroBLAST to generate input trees for a supertree reconstruction
      of the phylogeny of the Archaea. This independent analysis produces an
      approximate phylogeny of the Archaea that has both high precision and recall when
      compared to previously published analysis of the same dataset using conventional
      methods. Taken together these results demonstrate that approximate phylogenetic
      trees can be produced in the absence of multiple sequence alignments, and we
      propose that these trees will provide a platform for improving and informing
      downstream bioinformatic analysis. A web implementation of the DendroBLAST method
      is freely available for use at http://www.dendroblast.com/.

PMID- 23554900
TI  - Breast cancer and obesity: in vitro interferences between adipokines and
      proangiogenic features and/or antitumor therapies?
AB  - Obesity is now considered as a risk factor for breast cancer in postmenopausal
      women. Adipokine levels are modulated in obesity, and may play a role in
      carcinogenesis. Moreover, obesity increases risk of cancer mortality. Here, we
      hypothesized that this increase could be due to a modification in angiogenesis,
      capital event in the development of metastases, and/or in effectiveness of cancer
      treatments. To test these assumptions, following a same experimental design and
      simultaneously the effects of leptin and adiponectin on angiogenesis were
      investigated, and the impact of hyperleptinemia on anticancer drug effectiveness
      was measured in physiological and obesity situations. Focusing on angiogenesis,
      the proliferation of endothelial cells (HUVEC), which expressed leptin and
      adiponectin receptors, was stimulated by leptin and inhibited by adiponectin.
      Both adipokines globally reduced apoptosis and caspase activity. Leptin increased
      migration whereas adiponectin decreased migration, and leptin enhanced the area
      of the tubes formed by HUVEC cells while adiponectin inhibited their formation.
      MCF7 and MDA-MB-231 cells treated with leptin secreted more VEGF than untreated
      cells, whereas adiponectin treatment inhibited VEGF secretion. Finally, MCF7
      cells pre-treated with leptin were more invasive than untreated cells. This
      effect was not reproduced in MDA-MB-231 cells. In the MCF7 breast cancer cell
      line, leptin could induce cell proliferation and reduced the efficacy of all
      breast cancer therapies (tamoxifen, 5-fluorouracil, taxol and vinblastin). These
      results suggest that, in obesity situation, leptin- in contrast to adiponectin -
      may promote tumor invasion and angiogenesis, leading to metastases 'apparition,
      and reduce treatment efficacy, which could explain the increased risk of cancer
      mortality in cases of overweight. The evidence suggests adipokines influence
      breast cancer issue and could play a significant role, especially in obese
      patients for which hyperleptinemia, hypoadiponectinemia and increased metastatic
      potential are described.

PMID- 23554901
TI  - Increased toxicity of Karenia brevis during phosphate limited growth: ecological
      and evolutionary implications.
AB  - Karenia brevis is the dominant toxic red tide algal species in the Gulf of
      Mexico. It produces potent neurotoxins (brevetoxins [PbTxs]), which negatively
      impact human and animal health, local economies, and ecosystem function. Field
      measurements have shown that cellular brevetoxin contents vary from 1-68 pg/cell
      but the source of this variability is uncertain. Increases in cellular toxicity
      caused by nutrient-limitation and inter-strain differences have been observed in
      many algal species. This study examined the effect of P-limitation of growth rate
      on cellular toxin concentrations in five Karenia brevis strains from different
      geographic locations. Phosphorous was selected because of evidence for regional P
      limitation of algal growth in the Gulf of Mexico. Depending on the isolate, P
      limited cells had 2.3- to 7.3-fold higher PbTx per cell than P-replete cells. The
      percent of cellular carbon associated with brevetoxins (%C-PbTx) was ~ 0.7 to
      2.1% in P-replete cells, but increased to 1.6-5% under P-limitation. Because
      PbTxs are potent anti-grazing compounds, this increased investment in PbTxs
      should enhance cellular survival during periods of nutrient-limited growth. The
      %C-PbTx was inversely related to the specific growth rate in both the nutrient
      replete and P-limited cultures of all strains. This inverse relationship is
      consistent with an evolutionary tradeoff between carbon investment in PbTxs and
      other grazing defenses, and C investment in growth and reproduction. In aquatic
      environments where nutrient supply and grazing pressure often vary on different
      temporal and spatial scales, this tradeoff would be selectively advantageous as
      it would result in increased net population growth rates. The variation in
      PbTx/cell values observed in this study can account for the range of values
      observed in the field, including the highest values, which are not observed under
      N-limitation. These results suggest P-limitation is an important factor
      regulating cellular toxicity and adverse impacts during at least some K. brevis
      blooms.

PMID- 23554902
TI  - Genome and transcriptome analyses provide insight into the euryhaline adaptation
      mechanism of Crassostrea gigas.
AB  - BACKGROUND: The Pacific oyster, Crassostrea gigas, has developed special
      mechanisms to regulate its osmotic balance to adapt to fluctuations of salinities
      in coastal zones. To understand the oyster's euryhaline adaptation, we analyzed
      salt stress effectors metabolism pathways under different salinities (salt 5, 10,
      15, 20, 25, 30 and 40 for 7 days) using transcriptome data, physiology experiment
      and quantitative real-time PCR. RESULTS: Transcriptome data uncovered 189, 480,
      207 and 80 marker genes for monitoring physiology status of oysters and the
      environment conditions. Three known salt stress effectors (involving ion
      channels, aquaporins and free amino acids) were examined. The analysis of ion
      channels and aquaporins indicated that 7 days long-term salt stress inhibited
      voltage-gated Na(+)/K(+) channel and aquaporin but increased calcium-activated
      K(+) channel and Ca(2+) channel. As the most important category of osmotic stress
      effector, we analyzed the oyster FAAs metabolism pathways (including taurine,
      glycine, alanine, beta-alanine, proline and arginine) and explained FAAs
      functional mechanism for oyster low salinity adaptation. FAAs metabolism key
      enzyme genes displayed expression differentiation in low salinity adapted
      individuals comparing with control which further indicated that FAAs played
      important roles for oyster salinity adaptation. A global metabolic pathway
      analysis (iPath) of oyster expanded genes displayed a co-expansion of FAAs
      metabolism in C. gigas compared with seven other species, suggesting oyster's
      powerful ability regarding FAAs metabolism, allowing it to adapt to fluctuating
      salinities, which may be one important mechanism underlying euryhaline adaption
      in oyster. Additionally, using transcriptome data analysis, we uncovered salt
      stress transduction networks in C. gigas. CONCLUSIONS: Our results represented
      oyster salt stress effectors functional mechanisms under salt stress conditions
      and explained the expansion of FAAs metabolism pathways as the most important
      effectors for oyster euryhaline adaptation. This study was the first to explain
      oyster euryhaline adaptation at a genome-wide scale in C. gigas.

PMID- 23554903
TI  - A large-scale, higher-level, molecular phylogenetic study of the insect order
      Lepidoptera (moths and butterflies).
AB  - BACKGROUND: Higher-level relationships within the Lepidoptera, and particularly
      within the species-rich subclade Ditrysia, are generally not well understood,
      although recent studies have yielded progress. We present the most comprehensive
      molecular analysis of lepidopteran phylogeny to date, focusing on relationships
      among superfamilies. METHODOLOGY PRINCIPAL FINDINGS: 483 taxa spanning 115 of 124
      families were sampled for 19 protein-coding nuclear genes, from which maximum
      likelihood tree estimates and bootstrap percentages were obtained using GARLI.
      Assessment of heuristic search effectiveness showed that better trees and higher
      bootstrap percentages probably remain to be discovered even after 1000 or more
      search replicates, but further search proved impractical even with grid
      computing. Other analyses explored the effects of sampling nonsynonymous change
      only versus partitioned and unpartitioned total nucleotide change; deletion of
      rogue taxa; and compositional heterogeneity. Relationships among the non
      ditrysian lineages previously inferred from morphology were largely confirmed,
      plus some new ones, with strong support. Robust support was also found for
      divergences among non-apoditrysian lineages of Ditrysia, but only rarely so
      within Apoditrysia. Paraphyly for Tineoidea is strongly supported by analysis of
      nonsynonymous-only signal; conflicting, strong support for tineoid monophyly when
      synonymous signal was added back is shown to result from compositional
      heterogeneity. CONCLUSIONS SIGNIFICANCE: Support for among-superfamily
      relationships outside the Apoditrysia is now generally strong. Comparable support
      is mostly lacking within Apoditrysia, but dramatically increased bootstrap
      percentages for some nodes after rogue taxon removal, and concordance with other
      evidence, strongly suggest that our picture of apoditrysian phylogeny is
      approximately correct. This study highlights the challenge of finding optimal
      topologies when analyzing hundreds of taxa. It also shows that some nodes get
      strong support only when analysis is restricted to nonsynonymous change, while
      total change is necessary for strong support of others. Thus, multiple types of
      analyses will be necessary to fully resolve lepidopteran phylogeny.

PMID- 23554904
TI  - FOP is a centriolar satellite protein involved in ciliogenesis.
AB  - Centriolar satellites are proteinaceous granules that are often clustered around
      the centrosome. Although centriolar satellites have been implicated in protein
      trafficking in relation to the centrosome and cilium, the details of their
      function and composition remain unknown. FOP (FGFR1 Oncogene Partner) is a known
      centrosome protein with homology to the centriolar satellite proteins FOR20 and
      OFD1. We find that FOP partially co-localizes with the satellite component PCM1
      in a cell cycle-dependent manner, similarly to the satellite and cilium component
      BBS4. As for BBS4, FOP localization to satellites is cell cycle dependent, with
      few satellites labeled in G1, when FOP protein levels are lowest, and most
      labeled in G2. FOP-FGFR1, an oncogenic fusion that causes a form of leukemia
      called myeloproliferative neoplasm, also localizes to centriolar satellites where
      it increases tyrosine phosphorylation. Depletion of FOP strongly inhibits primary
      cilium formation in human RPE-1 cells. These results suggest that FOP is a
      centriolar satellite cargo protein and, as for several other satellite-associated
      proteins, is involved in ciliogenesis. Localization of the FOP-FGFR1 fusion
      kinase to centriolar satellites may be relevant to myeloproliferative neoplasm
      disease progression.

PMID- 23554905
TI  - RNA-seq reveals activation of both common and cytokine-specific pathways
      following neutrophil priming.
AB  - Neutrophils are central to the pathology of inflammatory diseases, where they can
      damage host tissue through release of reactive oxygen metabolites and proteases,
      and drive inflammation via secretion of cytokines and chemokines. Many cytokines,
      such as those generated during inflammation, can induce a similar "primed"
      phenotype in neutrophils, but it is unknown if different cytokines utilise common
      or cytokine-specific pathways to induce these functional changes. Here, we
      describe the transcriptomic changes induced in control human neutrophils during
      priming in vitro with pro-inflammatory cytokines (TNF-alpha and GM-CSF) using RNA
      seq. Priming led to the rapid expression of a common set of transcripts for
      cytokines, chemokines and cell surface receptors (CXCL1, CXCL2, IL1A, IL1B,
      IL1RA, ICAM1). However, 580 genes were differentially regulated by TNF-alpha and
      GM-CSF treatment, and of these 58 were directly implicated in the control of
      apoptosis. While these two cytokines both delayed apoptosis, they induced changes
      in expression of different pro- and anti-apoptotic genes. Bioinformatics analysis
      predicted that these genes were regulated via differential activation of
      transcription factors by TNF-alpha and GM-CSF and these predictions were
      confirmed using functional assays: inhibition of NF-kappaB signalling abrogated
      the protective effect of TNF-alpha (but not that of GM-CSF) on neutrophil
      apoptosis, whereas inhibition of JAK/STAT signalling abrogated the anti-apoptotic
      effect of GM-CSF, but not that of TNF-alpha (p<0.05). These data provide the
      first characterisation of the human neutrophil transcriptome following GM-CSF and
      TNF-alpha priming, and demonstrate the utility of this approach to define
      functional changes in neutrophils following cytokine exposure. This may provide
      an important, new approach to define the molecular properties of neutrophils
      after in vivo activation during inflammation.

PMID- 23554906
TI  - Transcription factor-microRNA-target gene networks associated with ovarian cancer
      survival and recurrence.
AB  - The identification of reliable transcriptome biomarkers requires the simultaneous
      consideration of regulatory and target elements including microRNAs (miRNAs),
      transcription factors (TFs), and target genes. A novel approach that integrates
      multivariate survival analysis, feature selection, and regulatory network
      visualization was used to identify reliable biomarkers of ovarian cancer survival
      and recurrence. Expression profiles of 799 miRNAs, 17,814 TFs and target genes
      and cohort clinical records on 272 patients diagnosed with ovarian cancer were
      simultaneously considered and results were validated on an independent group of
      146 patients. Three miRNAs (hsa-miR-16, hsa-miR-22*, and ebv-miR-BHRF1-2*) were
      associated with both ovarian cancer survival and recurrence and 27 miRNAs were
      associated with either one hazard. Two miRNAs (hsa-miR-521 and hsa-miR-497) were
      cohort-dependent, while 28 were cohort-independent. This study confirmed 19
      miRNAs previously associated with ovarian cancer and identified two miRNAs that
      have previously been associated with other cancer types. In total, the expression
      of 838 and 734 target genes and 12 and eight TFs were associated (FDR-adjusted P
      value <0.05) with ovarian cancer survival and recurrence, respectively.
      Functional analysis highlighted the association between cellular and nucleotide
      metabolic processes and ovarian cancer. The more direct connections and higher
      centrality of the miRNAs, TFs and target genes in the survival network studied
      suggest that network-based approaches to prognosticate or predict ovarian cancer
      survival may be more effective than those for ovarian cancer recurrence. This
      study demonstrated the feasibility to infer reliable miRNA-TF-target gene
      networks associated with survival and recurrence of ovarian cancer based on the
      simultaneous analysis of co-expression profiles and consideration of the clinical
      characteristics of the patients.

PMID- 23554908
TI  - Functional implications of microRNA-215 in TGF-beta1-induced phenotypic
      transition of mesangial cells by targeting CTNNBIP1.
AB  - Mesangial cell (MC) phenotypic transition is crucial for the progression of
      diabetic nephropathy. A major stimulus mediating high glucose-induced MC
      phenotypic transition is TGF-beta1. Our current study focuses on microRNA-215
      (miR-215) and investigates its role in TGF-beta1-mediated MC phenotypic
      transition. Using real-time quantitative PCR (qRT-PCR) and northern blotting, we
      determined that the miR-192/215 family is dramatically upregulated under diabetic
      conditions both in vitro and in vivo. Gain- and loss-of-function approaches
      demonstrated that miR-215 inhibition significantly inhibited TGF-beta1-induced
      mouse mesangial cell (MMC) phenotypic transition, whereas miR-215 upregulation
      promoted MMC phenotypic transition. Interestingly, these changes were not
      detected in cells that were treated with TGF-beta1 and miR-192 mimics or
      inhibitors. These results suggest that miR-215 participates in TGF-beta1-induced
      MMC phenotypic transition. Luciferase reporter assays were used to identify
      whether catenin-beta interacting protein 1 (CTNNBIP1) is a direct target of miR
      215, which was predicted by bioinformatic analysis. Mechanistic studies revealed
      that CTNNBIP1 suppresses Wnt/beta-catenin signaling and that miR-215 promotes
      beta-catenin activation and upregulates alpha-SMA and fibronectin expression in
      TGF-beta1-treated MMCs by targeting CTNNBIP1. In addition, in vivo miR-215
      silencing with a specific antagomir significantly increased CTNNBIP1 protein
      expression, resulting in reduced beta-catenin activity and decreased alpha-SMA
      and fibronectin expression in db/db mouse kidney glomeruli. Taken together, our
      findings indicate that miR-215 plays an essential role in MC phenotypic
      transition by regulating the CTNNBIP1/beta-catenin pathway, which is related to
      the pathogenesis of diabetic nephropathy.

PMID- 23554907
TI  - The Src-family kinase inhibitor PP2 rescues inducible differentiation events in
      emergent retinoic acid-resistant myeloblastic leukemia cells.
AB  - Retinoic acid is an embryonic morphogen and dietary factor that demonstrates
      chemotherapeutic efficacy in inducing maturation in leukemia cells. Using HL60
      model human myeloid leukemia cells, where all-trans retinoic acid (RA) induces
      granulocytic differentiation, we developed two emergent RA-resistant HL60 cell
      lines which are characterized by loss of RA-inducible G1/G0 arrest, CD11b
      expression, inducible oxidative metabolism and p47(phox) expression. However, RA
      treated RA-resistant HL60 continue to exhibit sustained MEK/ERK activation, and
      one of the two sequentially emergent resistant lines retains RA-inducible CD38
      expression. Other signaling events that define the wild-type (WT) response are
      compromised, including c-Raf phosphorylation and increased expression of c-Cbl,
      Vav1, and the Src-family kinases (SFKs) Lyn and Fgr. As shown previously in WT
      HL60 cells, we found that the SFK inhibitor PP2 significantly increases G1/G0
      cell cycle arrest, CD38 and CD11b expression, c-Raf phosphorylation and
      expression of the aforementioned regulators in RA-resistant HL60. The resistant
      cells were potentially incapable of developing inducible oxidative metabolism.
      These results motivate the concept that RA resistance can occur in steps, wherein
      growth arrest and other differentiation events may be recovered in both emergent
      lines. Investigating the mechanistic anomalies in resistant cell lines is of
      therapeutic significance and helps to mechanistically understand the response to
      retinoic acid's biological effects in WT HL60 cells.

PMID- 23554909
TI  - Restoration of miR-1228* expression suppresses epithelial-mesenchymal transition
      in gastric cancer.
AB  - Dysregulated miRNAs play critical roles during carcinogenesis and cancer
      progression. In the present study, the function of miR-1228* in regulating cancer
      progression was investigated in gastric cancer. Decreased expression of miR-1228*
      was observed in human gastric cancer tissues comparing to normal tissues.
      Subsequently, the role of miR-1228* was evaluated in vivo using the tumor
      xenograft model. In this model, miR-1228* overexpression suppressed xenograft
      tumor formation. Furthermore, we demonstrated miR-1228* negatively regulated NF
      kappaB activity in SGC-7901 gastric cancer cells and found that CK2A2 was a
      target of miR-1228*. Upregulation of miR-1228* decreased the expression of
      mesenchymal markers and increased the epithelial marker E-cadherin, suggesting
      its potential role in suppressing epithelial-mesenchymal transition.
      Collectively, these findings provide the first evidence that miR-1228* plays an
      important role in regulating gastric cancer growth and suggest that selective
      restoration of miR-1228* might be beneficial for gastric cancer therapy.

PMID- 23554911
TI  - Up-regulation of intestinal epithelial cell derived IL-7 expression by
      keratinocyte growth factor through STAT1/IRF-1, IRF-2 pathway.
AB  - BACKGROUND: Epithelial cells(EC)-derived interleukin-7 (IL-7) plays a crucial
      role in control of development and homeostasis of neighboring intraepithelial
      lymphocytes (IEL), and keratinocyte growth factor (KGF) exerts protective effects
      on intestinal epithelial cells and up-regulates EC-derived IL-7 expression
      through KGFR pathway. This study was to further investigate the molecular
      mechanism involved in the regulation of IL-7 expression by KGF in the intestine.
      METHODS: Intestinal epithelial cells (LoVo cells) and adult C57BL/6J mice were
      treated with KGF. Epithelial cell proliferation was studied by flow cytometry for
      BrdU-incorporation and by immunohistochemistry for PCNA staining. Western blot
      was used to detect the changes of expression of P-Tyr-STAT1, STAT1, and IL-7 by
      inhibiting STAT1. Alterations of nuclear extracts and total proteins of IRF-1,
      IRF-2 and IL-7 following IRF-1 and IRF-2 RNA interference with KGF treatment were
      also measured with western blot. Moreover, IL-7 mRNA expressions were also
      detected by Real-time PCR and IL-7 protein level in culture supernatants was
      measured by enzyme linked immunosorbent assay(ELISA). RESULTS: KGF administration
      significantly increased LoVo cell proliferation and also increased intestinal wet
      weight, villus height, crypt depth and crypt cell proliferation in mice. KGF
      treatment led to increased levels of P-Tyr-STAT1, RAPA and AG490 both blocked P
      Tyr-STAT1 and IL-7 expression in LoVo cells. IRF-1 and IRF-2 expression in vivo
      and in vitro were also up-regulated by KGF, and IL-7 expression was decreased
      after IRF-1 and IRF-2 expression was silenced by interfering RNA, respectively.
      CONCLUSION: KGF could up-regulate IL-7 expression through the STAT1/IRF-1, IRF-2
      signaling pathway, which is a new insight in potential effects of KGF on the
      intestinal mucosal immune system.

PMID- 23554910
TI  - First comparative transcriptomic analysis of wild adult male and female Lutzomyia
      longipalpis, vector of visceral leishmaniasis.
AB  - Leishmaniasis is a vector-borne disease with a complex epidemiology and ecology.
      Visceral leishmaniasis (VL) is its most severe clinical form as it results in
      death if not treated. In Latin America VL is caused by the protist parasite
      Leishmania infantum (syn. chagasi) and transmitted by Lutzomyia longipalpis. This
      phlebotomine sand fly is only found in the New World, from Mexico to Argentina.
      However, due to deforestation, migration and urbanisation, among others, VL in
      Latin America is undergoing an evident geographic expansion as well as dramatic
      changes in its transmission patterns. In this context, the first VL outbreak was
      recently reported in Argentina, which has already caused 7 deaths and 83 reported
      cases. Insect vector transcriptomic analyses enable the identification of
      molecules involved in the insect's biology and vector-parasite interaction.
      Previous studies on laboratory reared Lu. longipalpis have provided a descriptive
      repertoire of gene expression in the whole insect, midgut, salivary gland and
      male reproductive organs. Nevertheless, the study of wild specimens would
      contribute a unique insight into the development of novel bioinsecticides. Given
      the recent VL outbreak in Argentina and the compelling need to develop
      appropriate control strategies, this study focused on wild male and female Lu.
      longipalpis from an Argentine endemic (Posadas, Misiones) and a Brazilian non
      endemic (Lapinha Cave, Minas Gerais) VL location. In this study, total RNA was
      extracted from the sand flies, submitted to sequence independent amplification
      and high-throughput pyrosequencing. This is the first time an unbiased and
      comprehensive transcriptomic approach has been used to analyse an infectious
      disease vector in its natural environment. Transcripts identified in the sand
      flies showed characteristic profiles which correlated with the environment of
      origin and with taxa previously identified in these same specimens. Among these,
      various genes represented putative targets for vector control via RNA
      interference (RNAi).

PMID- 23554912
TI  - Dietary supplementation of blueberry juice enhances hepatic expression of
      metallothionein and attenuates liver fibrosis in rats.
AB  - AIM: To investigate the effect of blueberry juice intake on rat liver fibrosis
      and its influence on hepatic antioxidant defense. METHODS: Rabbiteye blueberry
      was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao
      hua-xian capsule (DSHX) was used as a positive control for liver fibrosis
      protection. Liver fibrosis was induced in male Sprague-Dawley rats by
      subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8
      weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of alpha
      smooth muscle actin (alpha-SMA) and collagen III (Col III) were determined by
      immunohistochemical techniques. The activities of superoxide dismutase (SOD) and
      malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT)
      expression was detected by real-time RT-PCR and immunohistochemical techniques.
      RESULTS: Blueberry juice consumption significantly attenuates CCl4-induced rat
      hepatic fibrosis, which was associated with elevated expression of
      metallothionein (MT), increased SOD activity, reduced oxidative stress, and
      decreased levels of alpha-SMA and Col III in the liver. CONCLUSION: Our study
      suggests that dietary supplementation of blueberry juice can augment
      antioxidative capability of the liver presumably via stimulating MT expression
      and SOD activity, which in turn promotes HSC inactivation and thus decreases
      extracellular matrix collagen accumulation in the liver, and thereby alleviating
      hepatic fibrosis.

PMID- 23554913
TI  - Construction of direction selectivity through local energy computations in
      primary visual cortex.
AB  - Despite detailed knowledge about the anatomy and physiology of neurons in primary
      visual cortex (V1), the large numbers of inputs onto a given V1 neuron make it
      difficult to relate them to the neuron's functional properties. For example,
      models of direction selectivity (DS), such as the Energy Model, can successfully
      describe the computation of phase-invariant DS at a conceptual level, while
      leaving it unclear how such computations are implemented by cortical circuits.
      Here, we use statistical modeling to derive a description of DS computation for
      both simple and complex cells, based on physiologically plausible operations on
      their inputs. We present a new method that infers the selectivity of a neuron's
      inputs using extracellular recordings in macaque in the context of random bar
      stimuli and natural movies in cat. Our results suggest that DS is initially
      constructed in V1 simple cells through summation and thresholding of non-DS
      inputs with appropriate spatiotemporal relationships. However, this de novo
      construction of DS is rare, and a majority of DS simple cells, and all complex
      cells, appear to receive both excitatory and suppressive inputs that are already
      DS. For complex cells, these numerous DS inputs typically span a fraction of
      their overall receptive fields and have similar spatiotemporal tuning but
      different phase and spatial positions, suggesting an elaboration to the Energy
      Model that incorporates spatially localized computation. Furthermore, we
      demonstrate how these computations might be constructed from biologically
      realizable components, and describe a statistical model consistent with the feed
      forward framework suggested by Hubel and Wiesel.

PMID- 23554915
TI  - Spatial distribution of tree species governs the spatio-temporal interaction of
      leaf area index and soil moisture across a forested landscape.
AB  - Quantifying coupled spatio-temporal dynamics of phenology and hydrology and
      understanding underlying processes is a fundamental challenge in ecohydrology.
      While variation in phenology and factors influencing it have attracted the
      attention of ecologists for a long time, the influence of biodiversity on coupled
      dynamics of phenology and hydrology across a landscape is largely untested. We
      measured leaf area index (L) and volumetric soil water content (theta) on a co
      located spatial grid to characterize forest phenology and hydrology across a
      forested catchment in central Pennsylvania during 2010. We used hierarchical
      Bayesian modeling to quantify spatio-temporal patterns of L and theta. Our
      results suggest that the spatial distribution of tree species across the
      landscape created unique spatio-temporal patterns of L, which created patterns of
      water demand reflected in variable soil moisture across space and time. We found
      a lag of about 11 days between increase in L and decline in theta. Vegetation and
      soil moisture become increasingly homogenized and coupled from leaf-onset to
      maturity but heterogeneous and uncoupled from leaf maturity to senescence. Our
      results provide insight into spatio-temporal coupling between biodiversity and
      soil hydrology that is useful to enhance ecohydrological modeling in humid
      temperate forests.

PMID- 23554914
TI  - Digital gene expression tag profiling analysis of the gene expression patterns
      regulating the early stage of mouse spermatogenesis.
AB  - Detailed characterization of the gene expression patterns in spermatogonia and
      primary spermatocytes is critical to understand the processes which occur prior
      to meiosis during normal spermatogenesis. The genome-wide expression profiles of
      mouse type B spermatogonia and primary spermatocytes were investigated using the
      Solexa/Illumina digital gene expression (DGE) system, a tag based high-throughput
      transcriptome sequencing method, and the developmental processes which occur
      during early spermatogenesis were systematically analyzed. Gene expression
      patterns vary significantly between mouse type B spermatogonia and primary
      spermatocytes. The functional analysis revealed that genes related to junction
      assembly, regulation of the actin cytoskeleton and pluripotency were most
      significantly differently expressed. Pathway analysis indicated that the Wnt non
      canonical signaling pathway played a central role and interacted with the actin
      filament organization pathway during the development of spermatogonia. This study
      provides a foundation for further analysis of the gene expression patterns and
      signaling pathways which regulate the molecular mechanisms of early
      spermatogenesis.

PMID- 23554916
TI  - Correlation of immunoglobulin G expression and histological subtype and stage in
      breast cancer.
AB  - INTRODUCTION: Recently, growing evidence indicates that immunoglobulins (Igs) are
      not only produced by mature B lymphocytes or plasma cells, but also by various
      normal cells types at immune privileged sites and neoplasm, including breast
      cancer. However, the association of breast cancer derived IgG with genesis and
      development of the disease has not yet been established. METHODS: In this study
      we examined the expression of IgG in 186 breast cancers, 20 benign breast lesions
      and 30 normal breast tissues. Both immunohistochemistry with antibodies to
      Igkappa (immunoglobulin G kappa light chain) and Iggamma (immunoglobulin G heavy
      chain) and in situ hybridization with an antisense probe to IgG1 heavy chain
      constant region gene were performed. Various clinicopathological features were
      also analyzed. RESULTS: We found that IgG is specifically expressed in human
      breast cancer cells. Both infiltrating ductal carcinoma and infiltrating lobular
      carcinoma had significantly greater numbers of Igkappa and Iggamma positive
      cancer cells as compared with medullary carcinoma, carcinoma in situ, and benign
      lesions (all p<0.05). In addition, IgG expression was correlated with breast
      cancer histological subtypes (p<0.01) and AJCC stages (p<0.05), with more
      abundance of IgG expression in more malignant histological subtypes or in more
      advanced stage of the disease. CONCLUSIONS: IgG expression in breast cancer cells
      is correlated with malignancy and AJCC stages of the cancers. This suggests that
      breast cancer derived IgG may be associated with genesis, development and
      prognosis of the cancer.

PMID- 23554917
TI  - Genetic variations in the serotoninergic system contribute to body-mass index in
      Chinese adolescents.
AB  - OBJECTIVE: Obesity has become a worldwide health problem in the past decades.
      Human and animal studies have implicated serotonin in appetite regulation, and
      behavior genetic studies have shown that body mass index (BMI) has a strong
      genetic component. However, the roles of genes related to the serotoninergic (5
      hydroxytryptamine,5-HT) system in obesity/BMI are not well understood, especially
      in Chinese subjects. SUBJECTS AND DESIGN: With a sample of 478 healthy Chinese
      volunteers, this study investigated the relation between BMI and genetic
      variations of the serotoninergic system as characterized by 136 representative
      polymorphisms. We used a system-level approach to identify SNPs associated with
      BMI, then estimated their overall contribution to BMI by multiple regression and
      verified it by permutation. RESULTS: We identified 12 SNPs that made
      statistically significant contributions to BMI. After controlling for gender and
      age, four of these SNPs accounted for 7.7% additional variance of BMI.
      Permutation analysis showed that the probability of obtaining these findings by
      chance was low (p = 0.015, permuted for 1000 times). CONCLUSION: These results
      showed that genetic variations in the serotoninergic system made a moderate
      contribution to individual differences in BMI among a healthy Chinese sample,
      suggesting that a similar approach can be used to study obesity.

PMID- 23554918
TI  - miR-141 contributes to fetal growth restriction by regulating PLAG1 expression.
AB  - BACKGROUND: Fetal growth restriction (FGR) is an important but poorly understood
      condition of pregnancy, which results in significant fetal, neonatal and long
      term morbidity and mortality. Novel research has suggested that altered miRNA
      expression in the plasma and placenta is associated with adverse pregnancy. We
      hypothesized that aberrant expression of microRNA-141 (miR-141) in the placenta
      is associated with FGR. Additionally, expression levels of predicted target genes
      of miR-141 were also analyzed in placental tissues of FGR and normal controls.
      METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative real time PCR, we analyzed the
      expression level of miR-141 and its target genes in placentas of FGR pregnancies
      (n = 21) and normal controls (n = 34). Western blot was used to detect the
      protein expression level of the target genes of miR-141. MiR-141 showed
      significant up regulation in FGR and significant down regulation of its targets,
      i.e. E2F transcription factor 3 (E2F3) protein, pleiomorphic adenoma gene 1
      (PLAG1) mRNA and protein. Moreover, a positive correlation was found between
      PLAG1 and insulin-like growth factor 2 (IGF2) expression levels (Spearman r =
      0.56, p<0.0001). MiR-141 yields an AUC of 0.83 with 88.5% sensitivity and 71.7%
      specificity for separating FGR from normal controls. This study indicates that
      miR-141 may be diagnostically important in FGR. CONCLUSIONS/SIGNIFICANCE: Our
      results indicate that aberrant high expression level of miR-141 might play
      important roles in the pathogenesis of FGR by suppressing E2F3 and PLAG1. We
      propose that miR-141 may participate in a miR-141-PLAG1-IGF2 network relating to
      FGR development. These findings may provide new targets via miR-141 in diagnosis
      and therapy of FGR in the future.

PMID- 23554919
TI  - Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype
      via Akt/FoxO/myocardin signaling.
AB  - BACKGROUND: Changes in the vascular smooth muscle cell (VSMC) contractile
      phenotype occur in pathological states such as restenosis and atherosclerosis.
      Multiple cytokines, signaling through receptor tyrosine kinases (RTK) and
      PI3K/Akt and MAPK/ERK pathways, regulate these phenotypic transitions. The Spry
      proteins are feedback modulators of RTK signaling, but their specific roles in
      VSMC have not been established. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report
      for the first time that Spry1, but not Spry4, is required for maintaining the
      differentiated state of human VSMC in vitro. While Spry1 is a known MAPK/ERK
      inhibitor in many cell types, we found that Spry1 has little effect on MAPK/ERK
      signaling but increases and maintains Akt activation in VSMC. Sustained Akt
      signaling is required for VSMC marker expression in vitro, while ERK signaling
      negatively modulates Akt activation and VSMC marker gene expression. Spry4, which
      antagonizes both MAPK/ERK and Akt signaling, suppresses VSMC differentiation
      marker gene expression. We show using siRNA knockdown and ChIP assays that
      FoxO3a, a downstream target of PI3K/Akt signaling, represses myocardin promoter
      activity, and that Spry1 increases, while Spry4 decreases myocardin mRNA levels.
      CONCLUSIONS: Together, these data indicate that Spry1 and Spry4 have opposing
      roles in VSMC phenotypic modulation, and Spry1 maintains the VSMC differentiation
      phenotype in vitro in part through an Akt/FoxO/myocardin pathway.

PMID- 23554920
TI  - Complete chloroplast genome sequence of holoparasite Cistanche deserticola
      (Orobanchaceae) reveals gene loss and horizontal gene transfer from its host
      Haloxylon ammodendron (Chenopodiaceae).
AB  - BACKGROUND: The central function of chloroplasts is to carry out photosynthesis,
      and its gene content and structure are highly conserved across land plants.
      Parasitic plants, which have reduced photosynthetic ability, suffer gene losses
      from the chloroplast (cp) genome accompanied by the relaxation of selective
      constraints. Compared with the rapid rise in the number of cp genome sequences of
      photosynthetic organisms, there are limited data sets from parasitic plants.
      PRINCIPAL FINDINGS/SIGNIFICANCE: Here we report the complete sequence of the cp
      genome of Cistanche deserticola, a holoparasitic desert species belonging to the
      family Orobanchaceae. The cp genome of C. deserticola is greatly reduced both in
      size (102,657 bp) and in gene content, indicating that all genes required for
      photosynthesis suffer from gene loss and pseudogenization, except for psbM. The
      striking difference from other holoparasitic plants is that it retains almost a
      full set of tRNA genes, and it has lower dN/dS for most genes than another close
      holoparasitic plant, E. virginiana, suggesting that Cistanche deserticola has
      undergone fewer losses, either due to a reduced level of holoparasitism, or to a
      recent switch to this life history. We also found that the rpoC2 gene was present
      in two copies within C. deserticola. Its own copy has much shortened and turned
      out to be a pseudogene. Another copy, which was not located in its cp genome, was
      a homolog of the host plant, Haloxylon ammodendron (Chenopodiaceae), suggesting
      that it was acquired from its host via a horizontal gene transfer.

PMID- 23554921
TI  - Age-dependent neuroplasticity mechanisms in Alzheimer Tg2576 mice following
      modulation of brain amyloid-beta levels.
AB  - The objective of this study was to investigate the effects of modulating brain
      amyloid-beta (Abeta) levels at different stages of amyloid pathology on synaptic
      function, inflammatory cell changes and hippocampal neurogenesis, i.e. processes
      perturbed in Alzheimer's disease (AD). Young (4- to 6-month-old) and older (15-
      to 18-month-old) APP(SWE) transgenic (Tg2576) mice were treated with the AD
      candidate drug (+)-phenserine for 16 consecutive days. We found significant
      reductions in insoluble Abeta1-42 levels in the cortices of both young and older
      transgenic mice, while significant reductions in soluble Abeta1-42 levels and
      insoluble Abeta1-40 levels were only found in animals aged 15-18 months.
      Autoradiography binding with the amyloid ligand Pittsburgh Compound B ((3)H-PIB)
      revealed a trend for reduced fibrillar Abeta deposition in the brains of older
      phenserine-treated Tg2576 mice. Phenserine treatment increased cortical
      synaptophysin levels in younger mice, while decreased interleukin-1beta and
      increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha
      levels were detected in the cortices of older mice. The reduction in Abeta1-42
      levels was associated with an increased number of bromodeoxyuridine-positive
      proliferating cells in the hippocampi of both young and older Tg2576 mice. To
      determine whether the increased cell proliferation was accompanied by increased
      neuronal production, the endogenous early neuronal marker doublecortin (DCX) was
      examined in the dentate gyrus (DG) using immunohistochemical detection. Although
      no changes in the total number of DCX(+)-expressing neurons were detected in the
      DG in Tg2576 mice at either age following (+)-phenserine treatment, dendritic
      arborization was increased in differentiating neurons in young Tg2576 mice.
      Collectively, these findings indicate that reducing Abeta1-42 levels in Tg2576
      mice at an early pathological stage affects synaptic function by modulating the
      maturation and plasticity of newborn neurons in the brain. In contrast, lowering
      Abeta levels in Tg2576 mice when Abeta plaque pathology is prominent mainly
      alters the levels of proinflammatory cytokines and chemokines.

PMID- 23554922
TI  - Noninvasive ultrasound molecular imaging of the effect of statins on endothelial
      inflammatory phenotype in early atherosclerosis.
AB  - BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible
      for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment
      of treatment-effects on endothelial inflammation may be of use for managing
      medical therapy and developing novel therapies. We hypothesized that molecular
      imaging of vascular cell adhesion molecule-1 (VCAM-1) with contrast enhanced
      ultrasound (CEU) could assess treatment effects on endothelial phenotype in early
      atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of
      the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age,
      mice received 8 weeks of regular chow or atorvastatin-enriched chow (10
      mg/kg/day). At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1
      expression was performed with VCAM-1-targeted (MB(VCAM)) and control microbubbles
      (MB(Ctr)). Aortic wall thickness was assessed with high frequency ultrasound.
      Histology, immunohistology and Western blot were used to assess plaque burden and
      VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1
      was reduced on Western blot by atorvastatin, which corresponded to less
      endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound
      did not detect differences in aortic wall thickness between groups. In contrast,
      CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM) in
      non-treated animals (MB(VCAM) 2+/-0.3 vs MB(Ctr) 0.7+/-0.2, p<0.01), but not in
      statin-treated animals (MB(VCAM) 0.8+/-0.2 vs MB(Ctr) 1.0+/-0.2, p = ns; p<0.01
      for the effect of statin on MB(VCAM) signal). CONCLUSIONS: Non-invasive CEU
      molecular imaging detects the effects of anti-inflammatory treatment on
      endothelial inflammation in early atherosclerosis. This easily accessible, low
      cost technique may be useful in assessing treatment effects in preclinical
      research and in patients.

PMID- 23554923
TI  - Bartonella quintana deploys host and vector temperature-specific transcriptomes.
AB  - The bacterial pathogen Bartonella quintana is passed between humans by body lice.
      B. quintana has adapted to both the human host and body louse vector niches,
      producing persistent infection with high titer bacterial loads in both the host
      (up to 10(5) colony-forming units [CFU]/ml) and vector (more than 10(8) CFU/ml).
      Using a novel custom microarray platform, we analyzed bacterial transcription at
      temperatures corresponding to the host (37 degrees C) and vector (28 degrees C),
      to probe for temperature-specific and growth phase-specific transcriptomes. We
      observed that transcription of 7% (93 genes) of the B. quintana genome is
      modified in response to change in growth phase, and that 5% (68 genes) of the
      genome is temperature-responsive. Among these transcriptional changes in response
      to temperature shift and growth phase was the induction of known B. quintana
      virulence genes and several previously unannotated genes. Hemin binding proteins,
      secretion systems, response regulators, and genes for invasion and cell
      attachment were prominent among the differentially-regulated B. quintana genes.
      This study represents the first analysis of global transcriptional responses by
      B. quintana. In addition, the in vivo experiments provide novel insight into the
      B. quintana transcriptional program within the body louse environment. These data
      and approaches will facilitate study of the adaptation mechanisms employed by
      Bartonella during the transition between human host and arthropod vector.

PMID- 23554924
TI  - Visualizing the topical structure of the medical sciences: a self-organizing map
      approach.
AB  - BACKGROUND: We implement a high-resolution visualization of the medical knowledge
      domain using the self-organizing map (SOM) method, based on a corpus of over two
      million publications. While self-organizing maps have been used for document
      visualization for some time, (1) little is known about how to deal with truly
      large document collections in conjunction with a large number of SOM neurons, (2)
      post-training geometric and semiotic transformations of the SOM tend to be
      limited, and (3) no user studies have been conducted with domain experts to
      validate the utility and readability of the resulting visualizations. Our study
      makes key contributions to all of these issues. METHODOLOGY: Documents extracted
      from Medline and Scopus are analyzed on the basis of indexer-assigned MeSH terms.
      Initial dimensionality is reduced to include only the top 10% most frequent terms
      and the resulting document vectors are then used to train a large SOM consisting
      of over 75,000 neurons. The resulting two-dimensional model of the high
      dimensional input space is then transformed into a large-format map by using
      geographic information system (GIS) techniques and cartographic design
      principles. This map is then annotated and evaluated by ten experts stemming from
      the biomedical and other domains. CONCLUSIONS: Study results demonstrate that it
      is possible to transform a very large document corpus into a map that is visually
      engaging and conceptually stimulating to subject experts from both inside and
      outside of the particular knowledge domain. The challenges of dealing with a
      truly large corpus come to the fore and require embracing parallelization and use
      of supercomputing resources to solve otherwise intractable computational tasks.
      Among the envisaged future efforts are the creation of a highly interactive
      interface and the elaboration of the notion of this map of medicine acting as a
      base map, onto which other knowledge artifacts could be overlaid.

PMID- 23554925
TI  - Composition and expression of genes encoding carbohydrate-active enzymes in the
      straw-degrading mushroom Volvariella volvacea.
AB  - Volvariella volvacea is one of a few commercial cultivated mushrooms mainly using
      straw as carbon source. In this study, the genome of V. volcacea was sequenced
      and assembled. A total of 285 genes encoding carbohydrate-active enzymes
      (CAZymes) in V. volvacea were identified and annotated. Among 15 fungi with
      sequenced genomes, V. volvacea ranks seventh in the number of genes encoding
      CAZymes. In addition, the composition of glycoside hydrolases in V. volcacea is
      dramatically different from other basidiomycetes: it is particularly rich in
      members of the glycoside hydrolase families GH10 (hemicellulose degradation) and
      GH43 (hemicellulose and pectin degradation), and the lyase families PL1, PL3 and
      PL4 (pectin degradation) but lacks families GH5b, GH11, GH26, GH62, GH93, GH115,
      GH105, GH9, GH53, GH32, GH74 and CE12. Analysis of genome-wide gene expression
      profiles of 3 strains using 3'-tag digital gene expression (DGE) reveals that 239
      CAZyme genes were expressed even in potato destrose broth medium. Our data also
      showed that the formation of a heterokaryotic strain could dramatically increase
      the expression of a number of genes which were poorly expressed in its parental
      homokaryotic strains.

PMID- 23554926
TI  - Care-seeking and management of common childhood illnesses in Tanzania--results
      from the 2010 Demographic and Health Survey.
AB  - BACKGROUND: Malaria, pneumonia and diarrhoea continue to kill millions of
      children in Africa despite the available and effective treatments. Correct
      diagnosis and prompt treatment with effective drugs at the first option consulted
      for child care is crucial for preventing severe disease and death from these
      illnesses. Using the 2010 Demographic and Health Survey data, the present study
      aims to assess care-seeking and management of suspected malaria, pneumonia and
      diarrhoea at various health care facilities in Tanzania. METHODS: We analyzed
      data for 8176 children born within a 5 years period preceding the survey.The
      information was collected by interviewing 5519 women aged 15-49 years in 10,300
      households selected from 475 sample points throughout Tanzania. RESULTS: The most
      common first option for child care was PHC facilities (54.8%), followed by
      private pharmacies (23.4%). These were more commonly utilized in rural compared
      to urban areas: 61.2% versus 34.5% for PHC facilities, and 26.5% versus 17.7% for
      pharmacies. Women in urban areas and those with higher level of education more
      commonly utilized higher level hospitals and private facilities as their first
      option for child care. Only one in four children with fever had received a blood
      test during the illness with lowest proportion being reported among children
      solely attended at PHC facilities. Use of abandoned antimalarial drugs for the
      treatment of suspected malaria was also observed in public health facilities and
      antibiotics use for diarrhoea treatment was high (49.0%). CONCLUSIONS: PHC
      facilities and pharmacies most commonly provided sub-optimal care. These
      facilities were more commonly utilized as the first option for child care in
      rural areas and among the poor and non-educated families. These are groups with
      the highest child mortality, which calls for interventions' targeting improvement
      of care at these facilities to further reduce child mortality from treatable
      illnesses in Tanzania.

PMID- 23554927
TI  - PLCz functional haplotypes modulating promoter transcriptional activity are
      associated with semen quality traits in Chinese Holstein bulls.
AB  - The sperm-specific phospholipase C zeta (PLCz) is a candidate sperm-borne oocyte
      activating factor that triggers a characteristic series of physiological stimuli
      via cytoplasmic Ca(2+) oscillations during fertilization. The molecular
      mechanisms involved in the regulation of PLCz gene expression remain largely
      unknown. To explore the genetic variations in the 5'-flanking region of the PLCz
      gene and their common haplotypes in Chinese Holstein bulls, as well as to
      determine whether these variations affect bovine semen quality traits and
      transcriptional activity, DNA samples were collected from Chinese Holstein bulls
      and sequenced for the identification of genetic variants in the 5'-flanking
      region of PLCz. Two genetic variants were identified, and their haplotypic
      profiles were constructed. The two novel genetic variations (g. -456 G>A and g.
      +65 T>C) were genotyped in 424 normal Chinese Holstein bulls. Bioinformatics
      analysis revealed that both loci are in transcription factor binding sites of the
      core promoter region. The association studies revealed that the two genetic
      variations and their haplotype combinations significantly affected semen quality
      traits. Using serially truncated constructs of the bovine PLCz promoters and the
      luciferase reporter, we found that a 726 bp (-641 nt to +112 nt) fragment
      constitutes the core promoter region. Furthermore, four haplotypes, H1H1 (GTGT),
      H2H2 (GCGC), H3H3 (ATAT), and H4H4 (ACAC), were significantly associated with
      semen quality traits and successfully transfected into MLTC-1 cell lines. The
      luciferase reporter assay showed that the different haplotypes exhibited distinct
      promoter activities. Maximal promoter activity was demonstrated by the H2H2
      haplotypes, as compared with the other haplotypes. To the best of our knowledge,
      this study is the first report on genetic variants and their respective
      haplotypes in the 5'-flanking region of PLCz gene that can influence the semen
      quality of Chinese Holstein bulls as well as contribute to the transcriptional
      activity of the PLCz promoter.

PMID- 23554929
TI  - Genetic diversity and evolution of Chinese traditional medicinal fungus Polyporus
      umbellatus (Polyporales, Basidiomycota).
AB  - BACKGROUND: Polyporus umbellatus is an important medicinal fungus distributed
      throughout most area of China. Its wide distribution may have resulted in
      substantial intraspecific genetic diversity for the fungus, potentially creating
      variation in its medical value. To date, we know little about the intraspecific
      genetic diversity of P. umbellatus. METHODOLOGY/PRINCIPAL FINDINGS: The objective
      of this research was to assess genetic differences of P. umbellatus from
      geographically diverse regions of China based on nrDNA ITS and 28S rRNA (LSU,
      large subunit) sequences. Significant sequence variations in the ITS and LSU
      sequences were detected. All sclerotial samples were clustered into four clades
      based on phylogenetic analysis of ITS, LSU and a combined data set of both
      regions. Heterogeneity of ITS and LSU sequences was detected in 5 and 7 samples
      respectively. All clone sequences clustered into the same clade except for one
      LSU clone sequences (from Henan province) which clustered into two clades (Clade
      I and Clade II). Significant genetic divergence in P. umbellatus was observed and
      the genetic diversification was greater among sclerotial samples from Shaanxi,
      Henan and Gansu provinces than among other provinces. Polymorphism of ITS and LSU
      sequences indicated that in China, P. umbellatus may spread from a center
      (Shaanxi, Henan and Gansu province) to other regions. CONCLUSIONS/SIGNIFICANCE:
      We found sclerotial samples of P. umbellatus contained levels of intraspecific
      genetic diversity. These findings suggested that P. umbellatus populations in
      Shaanxi, Henan and Gansu are important resources of genetic diversity and should
      be conserved accordingly.

PMID- 23554928
TI  - Tooth eruption results from bone remodelling driven by bite forces sensed by soft
      tissue dental follicles: a finite element analysis.
AB  - Intermittent tongue, lip and cheek forces influence precise tooth position, so we
      here examine the possibility that tissue remodelling driven by functional bite
      force-induced jaw-strain accounts for tooth eruption. Notably, although a
      separate true 'eruptive force' is widely assumed, there is little direct evidence
      for such a force. We constructed a three dimensional finite element model from
      axial computerized tomography of an 8 year old child mandible containing 12
      erupted and 8 unerupted teeth. Tissues modelled included: cortical bone,
      cancellous bone, soft tissue dental follicle, periodontal ligament, enamel,
      dentine, pulp and articular cartilage. Strain and hydrostatic stress during
      incisive and unilateral molar bite force were modelled, with force applied via
      medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain
      was maximal in the soft tissue follicle as opposed to surrounding bone,
      consistent with follicle as an effective mechanosensor. Initial numerical
      analysis of dental follicle soft tissue overlying crowns and beneath the roots of
      unerupted teeth was of volume and hydrostatic stress. To numerically evaluate
      biological significance of differing hydrostatic stress levels normalized for
      variable finite element volume, 'biological response units' in Nmm were defined
      and calculated by multiplication of hydrostatic stress and volume for each finite
      element. Graphical representations revealed similar overall responses for
      individual teeth regardless if incisive or right molar bite force was studied.
      There was general compression in the soft tissues over crowns of most unerupted
      teeth, and general tension in the soft tissues beneath roots. Not conforming to
      this pattern were the unerupted second molars, which do not erupt at this
      developmental stage. Data support a new hypothesis for tooth eruption, in which
      the follicular soft tissues detect bite-force-induced bone-strain, and direct
      bone remodelling at the inner surface of the surrounding bony crypt, with the
      effect of enabling tooth eruption into the mouth.

PMID- 23554930
TI  - Classify hyperdiploidy status of multiple myeloma patients using gene expression
      profiles.
AB  - Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently
      harbors alterations in DNA and chromosome copy numbers, and can be divided into
      two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma
      (NHMM). The two subtypes have different survival prognosis, possibly due to
      different but converging paths to oncogenesis. Existing methods for identifying
      the two subtypes are fluorescence in situ hybridization (FISH) and copy number
      microarrays, with increased cost and sample requirements. We hypothesize that
      chromosome alterations have their imprint in gene expression through dosage
      effect. Using five MM expression datasets that have HMM status measured by FISH
      and copy number microarrays, we have developed and validated a K-nearest-neighbor
      method to classify MM into HMM and NHMM based on gene expression profiles.
      Classification accuracy for test datasets ranges from 0.83 to 0.88. This
      classification will enable researchers to study differences and commonalities of
      the two MM subtypes in disease biology and prognosis using expression datasets
      without need for additional subtype measurements. Our study also supports the
      advantages of using cancer specific characteristics in feature design and pooling
      multiple rounds of classification results to improve accuracy. We provide R
      source code and processed datasets at www.ChengLiLab.org/software.

PMID- 23554931
TI  - Joint loads in marsupial ankles reflect habitual bipedalism versus
      quadrupedalism.
AB  - Joint surfaces of limb bones are loaded in compression by reaction forces
      generated from body weight and musculotendon complexes bridging them. In general,
      joints of eutherian mammals have regions of high radiodensity subchondral bone
      that are better at resisting compressive forces than low radiodensity subchondral
      bone. Identifying similar form-function relationships between subchondral
      radiodensity distribution and joint load distribution within the marsupial
      postcranium, in addition to providing a richer understanding of marsupial
      functional morphology, can serve as a phylogenetic control in evaluating
      analogous relationships within eutherian mammals. Where commonalities are
      established across phylogenetic borders, unifying principles in mammalian
      physiology, morphology, and behavior can be identified. Here, we assess
      subchondral radiodensity patterns in distal tibiae of several marsupial taxa
      characterized by different habitual activities (e.g., locomotion). Computed
      tomography scanning, maximum intensity projection maps, and pixel counting were
      used to quantify radiodensity in 41 distal tibiae of bipedal (5 species),
      arboreal quadrupedal (4 species), and terrestrial quadrupedal (5 species)
      marsupials. Bipeds (Macropus and Wallabia) exhibit more expansive areas of high
      radiodensity in the distal tibia than arboreal (Dendrolagus, Phascolarctos, and
      Trichosurus) or terrestrial quadrupeds (Sarcophilus, Thylacinus, Lasiorhinus, and
      Vombatus), which may reflect the former carrying body weight only through the
      hind limbs. Arboreal quadrupeds exhibit smallest areas of high radiodensity,
      though they differ non-significantly from terrestrial quadrupeds. This could
      indicate slightly more compliant gaits by arboreal quadrupeds compared to
      terrestrial quadrupeds. The observed radiodensity patterns in marsupial tibiae,
      though their statistical differences disappear when controlling for phylogeny,
      corroborate previously documented patterns in primates and xenarthrans,
      potentially reflecting inferred limb use during habitual activities such as
      locomotion. Despite the complex nature of factors contributing to joint loads,
      broad observance of these patterns across joints and across a variety of taxa
      suggests that subchondral radiodensity can be used as a unifying form-function
      principle within Mammalia.

PMID- 23554932
TI  - The impact of HAART on the respiratory complications of HIV infection:
      longitudinal trends in the MACS and WIHS cohorts.
AB  - OBJECTIVE: To review the incidence of respiratory conditions and their effect on
      mortality in HIV-infected and uninfected individuals prior to and during the era
      of highly active antiretroviral therapy (HAART). DESIGN: Two large observational
      cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study
      [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and
      1994, respectively. METHODS: Adjusted odds or hazards ratios for incident
      respiratory infections or non-infectious respiratory diagnoses, respectively, in
      HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS
      only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality
      in HIV-infected persons with lung disease during the HAART era. RESULTS: Compared
      to HIV-uninfected participants, HIV-infected individuals had more incident
      respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95%
      confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS,
      adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7;
      p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV
      infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR]
      2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung
      diseases were not significantly more common in HIV-infected participants in
      either MACS or WIHS participants. HIV-infected participants in the HAART era with
      respiratory infections had an increased risk of death compared to those without
      infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR,
      1.9; 95%CI, 1.5-2.4; p<0.001). CONCLUSION: HIV infection remained a significant
      risk for infectious respiratory diseases after the introduction of HAART, and
      infectious respiratory diseases were associated with an increased risk of
      mortality.

PMID- 23554933
TI  - Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention
      trials.
AB  - There is considerable interest in designing therapeutic studies of individuals at
      risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical beta
      amyloid plaques, the first stage of AD pathology, can be detected in vivo using
      positron emission tomography (PET), and several studies have shown that ~1/3 of
      healthy elderly have significant beta-amyloid deposition. Here we assessed
      whether asymptomatic amyloid-PET-positive controls have increased rates of brain
      atrophy, which could be harnessed as an outcome measure for AD prevention trials.
      We assessed 66 control subjects (age = 73.5+/-7.3 yrs; MMSE = 29+/-1.3) from the
      Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh
      Compound B (PiB) PET scan and two 3T MRI scans ~18-months apart. We calculated
      PET standard uptake value ratios (SUVR), and classified individuals as amyloid
      positive/negative. Baseline and 18-month MRI scans were registered, and brain,
      hippocampal, and ventricular volumes and annualized volume changes calculated.
      Increasing baseline PiB-PET measures of beta-amyloid load correlated with
      hippocampal atrophy rate independent of age (p = 0.014). Twenty-two (1/3) were
      PiB-positive (SUVR>1.40), the remaining 44 PiB-negative (SUVR<=1.31). Compared to
      PiB-negatives, PiB-positive individuals were older (76.8+/-7.5 vs. 71.7+/-7.5,
      p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no
      differences in baseline brain, ventricle or hippocampal volumes, either with or
      without correction for total intracranial volume, once age and gender were
      accounted for. The PiB-positive group had greater total hippocampal loss (0.06+/
      0.08 vs. 0.02+/-0.05 ml/yr, p = 0.02), independent of age and gender, with non
      significantly higher rates of whole brain (7.1+/-9.4 vs. 4.7+/-5.5 ml/yr) and
      ventricular (2.0+/-3.0 vs. 1.1+/-1.0 ml/yr) change. Based on the observed effect
      size, recruiting 384 (95%CI 195-1080) amyloid-positive subjects/arm will provide
      80% power to detect 25% absolute slowing of hippocampal atrophy rate in an 18
      month treatment trial. We conclude that hippocampal atrophy may be a feasible
      outcome measure for secondary prevention studies in asymptomatic amyloidosis.

PMID- 23554934
TI  - Eyes absent tyrosine phosphatase activity is not required for Drosophila
      development or survival.
AB  - Eyes absent (Eya) is an evolutionarily conserved transcriptional coactivator and
      protein phosphatase that regulates multiple developmental processes throughout
      the metazoans. Drosophila eya is necessary for survival as well as for the
      formation of the adult eye. Eya contains a tyrosine phosphatase domain, and
      mutations altering presumptive active-site residues lead to strongly reduced
      activities in ectopic eye induction, in vivo genetic rescue using the Gal4-UAS
      system, and in vitro phosphatase assays. However, these mutations have not been
      analyzed during normal development with the correct levels, timing, and patterns
      of endogenous eya expression. To investigate whether the tyrosine phosphatase
      activity of Eya plays a role in Drosophila survival or normal eye formation, we
      generated three eya genomic rescue (eyaGR) constructs that alter key active-site
      residues and tested them in vivo. In striking contrast to previous studies, all
      eyaGR constructs fully restore eye formation as well as viability in an eya null
      mutant background. We conclude that the tyrosine phosphatase activity of Eya is
      not required for normal eye development or survival in Drosophila. Our study
      suggests the need for a re-evaluation of the mechanism of Eya action and
      underscores the importance of studying genes in their native context.

PMID- 23554935
TI  - The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease:
      the BISCUIT study.
AB  - INTRODUCTION: Children presenting for the first time with inflammatory bowel
      disease (IBD) offer a unique opportunity to study aetiological agents before the
      confounders of treatment. Microaerophilic bacteria can exploit the ecological
      niche of the intestinal epithelium; Helicobacter and Campylobacter are previously
      implicated in IBD pathogenesis. We set out to study these and other
      microaerophilic bacteria in de-novo paediatric IBD. PATIENTS AND METHODS: 100
      children undergoing colonoscopy were recruited including 44 treatment naive de
      novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to
      microaerophilic culture with Gram-negative isolates then identified by
      sequencing. Biopsies were also PCR screened for the specific microaerophilic
      bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella
      wadsworthensis. RESULTS: 129 Gram-negative microaerophilic bacterial isolates
      were identified from 10 genera. The most frequently cultured was S.
      wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8
      subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C.
      showae). No Helicobacter were cultured. When comparing IBD vs. normal colon
      control by PCR the prevalence figures were not significantly different
      (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S.
      wadsworthensis 82% vs. 71%, p = 0.312). CONCLUSIONS: This study offers a
      comprehensive overview of the microaerophilic microbiota of the paediatric colon
      including at IBD onset. Campylobacter appear to be surprisingly common, are not
      more strongly associated with IBD and can be isolated from around 8% of
      paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal.
      Helicobacter species are relatively rare in the paediatric colon. TRIAL
      REGISTRATION: This study is publically registered on the United Kingdom Clinical
      Research Network Portfolio (9633).

PMID- 23554936
TI  - Visceral endoderm expression of Yin-Yang1 (YY1) is required for VEGFA maintenance
      and yolk sac development.
AB  - Mouse embryos lacking the polycomb group gene member Yin-Yang1 (YY1) die during
      the peri-implantation stage. To assess the post-gastrulation role of YY1, a
      conditional knock-out (cKO) strategy was used to delete YY1 from the visceral
      endoderm of the yolk sac and the definitive endoderm of the embryo. cKO embryos
      display profound yolk sac defects at 9.5 days post coitum (dpc), including
      disrupted angiogenesis in mesoderm derivatives and altered epithelial
      characteristics in the visceral endoderm. Significant changes in both cell death
      and proliferation were confined to the YY1-expressing yolk sac mesoderm
      indicating that loss of YY1 in the visceral endoderm causes defects in the
      adjacent yolk sac mesoderm. Production of Vascular Endothelial Growth Factor A
      (VEGFA) by the visceral endoderm is essential for normal growth and development
      of the yolk sac vasculature. Reduced levels of VEGFA are observed in the cKO yolk
      sac, suggesting a cause for the angiogenesis defects. Ex vivo culture with
      exogenous VEGF not only rescued angiogenesis and apoptosis in the cKO yolk sac
      mesoderm, but also restored the epithelial defects observed in the cKO visceral
      endoderm. Intriguingly, blocking the activity of the mesoderm-localized VEGF
      receptor, FLK1, recapitulates both the mesoderm and visceral endoderm defects
      observed in the cKO yolk sac. Taken together, these results demonstrate that YY1
      is responsible for maintaining VEGF in the developing visceral endoderm and that
      a VEGF-responsive paracrine signal, originating in the yolk sac mesoderm, is
      required to promote normal visceral endoderm development.

PMID- 23554938
TI  - An ornithomimid (Dinosauria) bonebed from the Late Cretaceous of Alberta, with
      implications for the behavior, classification, and stratigraphy of North American
      ornithomimids.
AB  - Bonebeds can provide a wealth of anatomical, taphonomic, and ontogenetic
      information about the specimens preserved within them, and can provide evidence
      for inferred behavior. The material described here represents the first known
      bonebed of ornithomimids in North America, and the fourth record of an
      ornithomimosaur bonebed in the world. Partial skeletons representing three
      individuals are preserved in this assemblage, each comprising primarily portions
      of the posterior postcrania (pelvis, hind limbs and tail). All three individuals
      are morphologically similar, although one is larger in overall size. Given the
      stratigraphic position of the site, and the morphology of the postcrania, the
      preserved material represents a taxon from the clade containing Ornithomimus and
      Struthiomimus. Pedal ungual morphology is examined and found to be too variable
      to be useful in distinguishing these species taxonomically. This site provides
      additional evidence of gregarious behavior in ornithomimids and the first
      probable record of that behavior in North American forms.

PMID- 23554937
TI  - Cholesterol biosynthesis and homeostasis in regulation of the cell cycle.
AB  - The cell cycle is a ubiquitous, multi-step process that is essential for growth
      and proliferation of cells. The role of membrane lipids in cell cycle regulation
      is not explored well, although a large number of cytoplasmic and nuclear
      regulators have been identified. We focus in this work on the role of membrane
      cholesterol in cell cycle regulation. In particular, we have explored the
      stringency of the requirement of cholesterol in the regulation of cell cycle
      progression. For this purpose, we utilized distal and proximal inhibitors of
      cholesterol biosynthesis, and monitored their effect on cell cycle progression.
      We show that cholesterol content increases in S phase and inhibition of
      cholesterol biosynthesis results in cell cycle arrest in G1 phase under certain
      conditions. Interestingly, G1 arrest mediated by cholesterol biosynthesis
      inhibitors could be reversed upon metabolic replenishment of cholesterol.
      Importantly, our results show that the requirement of cholesterol for G1 to S
      transition is absolute, and even immediate biosynthetic precursors of
      cholesterol, differing with cholesterol merely in a double bond, could not
      replace cholesterol for reversing the cell cycle arrest. These results are useful
      in the context of diseases, such as cancer and Alzheimer's disease, that are
      associated with impaired cholesterol biosynthesis and homeostasis.

PMID- 23554939
TI  - Osbpl8 deficiency in mouse causes an elevation of high-density lipoproteins and
      gender-specific alterations of lipid metabolism.
AB  - OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum
      sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8(-/
      ) (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13
      weeks were fed for 5 weeks either chow or high-fat diet, and their plasma
      lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male
      mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol
      (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I
      (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of
      HDL cholesterol (+27%) was observed, while on western diet the HDL increment was
      prominent in both genders. The HDL increase was accompanied by an elevated level
      of HDL-associated apolipoprotein E in male, but not female KO animals. No
      differences between genotypes were observed in lecithin:cholesterol
      acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional
      catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed
      animals. The Osbpl8KO mice of both genders displayed reduced phospholipid
      transfer protein (PLTP) activity, but only on chow diet. These findings are
      consistent with a model in which Osbpl8 deficiency results in altered
      biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse
      hepatocytes secreted an increased amount of nascent HDL into the culture medium.
      In addition to the HDL phenotype, distinct gender-specific alterations in lipid
      metabolism were detected: Female KO animals on chow diet showed reduced
      lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the
      male KO mice displayed elevated plasma cholesterol biosynthetic markers
      cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific
      alterations in the hepatic expression of lipid homeostatic genes were observed.
      In conclusion, we report the first viable OsbplKO mouse model, demonstrating a
      HDL elevating effect of Osbpl8 knock-out and additional gender- and/or diet
      dependent impacts on lipid metabolism.

PMID- 23554941
TI  - Val-boroPro accelerates T cell priming via modulation of dendritic cell
      trafficking resulting in complete regression of established murine tumors.
AB  - Although tumors naturally prime adaptive immune responses, tolerance may limit
      the capacity to control progression and can compromise effectiveness of immune
      based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein
      function through N-terminal dipeptide cleavage and inhibition of these enzymes
      has been shown to have anti-tumor activity. We investigated the mechanism by
      which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving
      enzymes, mediates tumor regression and tested whether this agent could serve as a
      novel immune adjuvant to dendritic cell vaccines in two different murine
      syngeneic murine tumors. In mice challenged with MB49, which expresses the HY
      antigen complex, T cell responses primed by the tumor with and without Val
      boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene
      deficient mice were used to establish the immune cell subsets required for tumor
      regression. We demonstrate that Val-boroPro mediates tumor eradication by
      accelerating the expansion of tumor-specific T cells. Interestingly, T cells
      primed by tumor during Val-boroPro treatment demonstrate increased capacity to
      reject tumors following adoptive transfer without further treatment of the
      recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is
      associated with enhanced trafficking of dendritic cells to tumor draining lymph
      nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment
      results in complete regression of established tumors. Our findings demonstrate
      that Val-boroPro has antitumor activity and a novel mechanism of action that
      involves more robust DC trafficking with earlier priming of T cells. Finally, we
      show that Val-boroPro has potent adjuvant properties resulting in an effective
      therapeutic vaccine.

PMID- 23554940
TI  - Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis
      and hematopoiesis.
AB  - Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior
      vertebral column, but are viable and fertile. Here, we report that zebrafish
      embryos having decreased function of the orthologous hoxd4a gene manifest
      striking perturbations in vasculogenesis, angiogenesis and primitive and
      definitive hematopoiesis. These defects are preceded by reduced expression of the
      hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate
      mesoderm (PLM) at 13 hours post fertilization (hpf). Epistasis analysis revealed
      that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as early as the
      shield stage in ventral-most mesoderm fated to give rise to hemangioblasts,
      leading us to propose that loss of hoxd4a function disrupts hemangioblast
      specification. These findings place hoxd4a high in a genetic hierarchy directing
      hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An
      additional consequence of impaired hoxd4a and meis1.1 expression is the
      deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis
      which may further contribute to the defects described here. Our results add to
      evidence implicating key roles for Hox genes in their initial phase of expression
      early in gastrulation.

PMID- 23554942
TI  - Does exercise improve glycaemic control in type 1 diabetes? A systematic review
      and meta-analysis.
AB  - OBJECTIVE: Whilst regular exercise is advocated for people with type 1 diabetes,
      the benefits of this therapy are poorly delineated. Our objective was to review
      the evidence for a glycaemic benefit of exercise in type 1 diabetes. RESEARCH
      DESIGN AND METHODS: Electronic database searches were carried out in MEDLINE,
      Embase, Cochrane's Controlled Trials Register and SPORTDiscus. In addition, we
      searched for as yet unpublished but completed trials. Glycaemic benefit was
      defined as an improvement in glycosylated haemoglobin (HbA1c). Both randomised
      and non-randomised controlled trials were included. RESULTS: Thirteen studies
      were identified in the systematic review. Meta-analysis of twelve of these
      (including 452 patients) demonstrated an HbA1c reduction but this was not
      statistically significant (standardised mean difference (SMD) -0.25; 95% CI, 
      0.59 to 0.09). CONCLUSIONS: This meta-analysis does not reveal evidence for a
      glycaemic benefit of exercise as measured by HbA1c. Reasons for this finding
      could include increased calorie intake, insulin dose reductions around the time
      of exercise or lack of power. We also suggest that HbA1c may not be a sensitive
      indicator of glycaemic control, and that improvement in glycaemic variability may
      not be reflected in this measure. Exercise does however have other proven
      benefits in type 1 diabetes, and remains an important part of its management.

PMID- 23554943
TI  - The interplay between chondrocyte redifferentiation pellet size and oxygen
      concentration.
AB  - Chondrocytes dedifferentiate during ex vivo expansion on 2-dimensional surfaces.
      Aggregation of the expanded cells into 3-dimensional pellets, in the presence of
      induction factors, facilitates their redifferentiation and restoration of the
      chondrogenic phenotype. Typically 1*10(5)-5*10(5) chondrocytes are aggregated,
      resulting in "macro" pellets having diameters ranging from 1-2 mm. These
      macropellets are commonly used to study redifferentiation, and recently
      macropellets of autologous chondrocytes have been implanted directly into
      articular cartilage defects to facilitate their repair. However, diffusion of
      metabolites over the 1-2 mm pellet length-scales is inefficient, resulting in
      radial tissue heterogeneity. Herein we demonstrate that the aggregation of
      2*10(5) human chondrocytes into micropellets of 166 cells each, rather than into
      larger single macropellets, enhances chondrogenic redifferentiation. In this
      study, we describe the development of a cost effective fabrication strategy to
      manufacture a microwell surface for the large-scale production of micropellets.
      The thousands of micropellets were manufactured using the microwell platform,
      which is an array of 360*360 um microwells cast into polydimethylsiloxane (PDMS),
      that has been surface modified with an electrostatic multilayer of hyaluronic
      acid and chitosan to enhance micropellet formation. Such surface modification was
      essential to prevent chondrocyte spreading on the PDMS. Sulfated
      glycosaminoglycan (sGAG) production and collagen II gene expression in
      chondrocyte micropellets increased significantly relative to macropellet
      controls, and redifferentiation was enhanced in both macro and micropellets with
      the provision of a hypoxic atmosphere (2% O2). Once micropellet formation had
      been optimized, we demonstrated that micropellets could be assembled into larger
      cartilage tissues. Our results indicate that micropellet amalgamation efficiency
      is inversely related to the time cultured as discreet microtissues. In summary,
      we describe a micropellet production platform that represents an efficient tool
      for studying chondrocyte redifferentiation and demonstrate that the micropellets
      could be assembled into larger tissues, potentially useful in cartilage defect
      repair.

PMID- 23554944
TI  - In vivo detection of human TRPV6-rich tumors with anti-cancer peptides derived
      from soricidin.
AB  - Soricidin is a 54-amino acid peptide found in the paralytic venom of the northern
      short-tailed shrew (Blarina brevicauda) and has been found to inhibit the
      transient receptor potential of vallinoid type 6 (TRPV6) calcium channels. We
      report that two shorter peptides, SOR-C13 and SOR-C27, derived from the C
      terminus of soricidin, are high-affinity antagonists of human TRPV6 channels that
      are up-regulated in a number of cancers. Herein, we report molecular imaging
      methods that demonstrate the in vivo diagnostic potential of SOR-C13 and SOR-C27
      to target tumor sites in mice bearing ovarian or prostate tumors. Our results
      suggest that these novel peptides may provide an avenue to deliver diagnostic and
      therapeutic reagents directly to TRPV6-rich tumors and, as such, have potential
      applications for a range of carcinomas including ovarian, breast, thyroid,
      prostate and colon, as well as certain leukemia's and lymphomas.

PMID- 23554945
TI  - Nitric oxide as a biomarker of intracellular Salmonella viability and
      identification of the bacteriostatic activity of protein kinase A inhibitor H-89.
AB  - Salmonella enterica serovar Enteritidis is one of the most prevalent Salmonella
      serovars in poultry and is often associated with human salmonellosis. S.
      Enteritidis is known to suppress nitric oxide (NO) production in infected chicken
      macrophage HD11 cells, while dead S. Enteritidis stimulates a high level of NO
      production, suggesting a bacterial inhibitory effect on NO production. Based on
      these observations, the present study was conducted to evaluate whether NO
      production in S. Enteritidis-infected HD11 cells can be used as a biomarker to
      identify molecules that kill intracellular Salmonella. Since Salmonella are known
      to manipulate the host cell kinase network to facilitate intracellular survival,
      we screened a group of pharmaceutical inhibitors of various kinases to test our
      hypothesis. A protein kinase A inhibitor, H-89, was found to reverse the
      suppression of NO production in S. Enteritidis-infected HD11 cells. Production of
      NO in S. Enteritidis-infected HD11 cells increased significantly following
      treatment with H-89 at or above 20 uM. Inversely, the number of viable
      intracellular Salmonella decreased significantly in cells treated with H-89 at or
      above 30 uM. Furthermore, the growth rate of S. Enteritidis in culture was
      significantly inhibited by H-89 at concentrations from 20 to 100 uM. Our results
      demonstrate that NO-based screening using S. Enteritidis-infected HD11 cells is a
      viable tool to identify chemicals with anti-intracellular Salmonella activity.
      Using this method, we have shown H-89 has bacteriostatic activity against
      Salmonella, independent of host cell protein kinase A or Akt1 activity.

PMID- 23554946
TI  - Drosophila bestrophin-1 currents are regulated by phosphorylation via a CaMKII
      dependent mechanism.
AB  - Cell swelling induced by hypo-osmotic stress results in activation of volume
      regulated anion channels (VRAC) that drive a compensatory regulatory volume
      decrease. We have previously shown that the Best1 gene in Drosophila encodes a
      VRAC that is also activated by increases in intracellular Ca(2+). The role of
      Best1 as a VRAC has recently been independently confirmed by the Clapham lab in
      an unbiased RNAi screen. Although dBest1 is clearly a volume-regulated channel,
      its mechanisms of regulation remain unknown. Here we investigate Drosophila Best1
      (dBest1) regulation using the Drosophila S2 cell model system. Because dBest1
      activates slowly after establishing whole-cell recording, we tested the
      hypothesis that the channel is activated by phosphorylation. Two experiments
      indicate that phosphorylation is required for dBest1 activation: nonspecific
      protein kinase inhibitors or intracellular perfusion with the non-hydrolyzable
      ATP analog AMP-PNP dramatically reduce the amplitude of dBest1 currents.
      Furthermore, intracellular perfusion with ATP-gamma-S augments channel
      activation. The kinase responsible for dBest1 activation is likely
      Ca(2+)/calmodulin dependent kinase II (CaMKII), because specific inhibitors of
      this kinase dramatically inhibit dBest1 current activation. Neither specific PKA
      inhibitors nor inactive control inhibitors have effects on dBest1currents. Our
      results demonstrate that dBest1 currents are regulated by phosphorylation via a
      CaMKII dependent mechanism.

PMID- 23554947
TI  - Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal
      prostate epithelial cell.
AB  - Recent studies underline the implication of Liver X Receptors (LXRs) in several
      prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer.
      In order to understand the molecular mechanisms involved, we derived epithelial
      cells from dorsal prostate (MPECs) of wild type (WT) or Lxralphabeta-/- mice. In
      the WT MPECs, our results show that LXR activation reduces proliferation and
      correlates with the modification of the AKT-survival pathway. Moreover, LXRs
      regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in
      a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxralphabeta
      /- mice show a higher basal phosphorylation and consequently activation of the
      survival/proliferation transduction pathways AKT and MAPK. Altogether, our data
      point out that the cell model we developed allows deciphering the molecular
      mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs
      regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be
      good pharmacological targets in prostate disease such as cancer.

PMID- 23554948
TI  - Report on use of a methodology for commissioning and quality assurance of a VMAT
      system.
AB  - INTRODUCTION: Results of use of methodology for VMAT commissioning and quality
      assurance, utilizing both control point tests and dosimetric measurements are
      presented. METHODS AND MATERIALS: A generalizable, phantom measurement approach
      is used to characterize the accuracy of the measurement system. Correction for
      angular response of the measurement system and inclusion of couch structures are
      used to characterize the full range gantry angles desirable for clinical plans. A
      dose based daily QA measurement approach is defined. RESULTS: Agreement in the
      static vs. VMAT picket fence control point test was better than 0.5 mm. Control
      point tests varying gantry rotation speed, leaf speed and dose rate, demonstrated
      agreement with predicted values better than 1%. Angular dependence of the MatriXX
      array, varied over a range of 0.94-1.06, with respect to the calibration
      condition. Phantom measurements demonstrated central axis dose accuracy for un
      modulated four field box plans was >=2.5% vs. 1% with and without angular
      correction respectively with better results for VMAT (0.4%) vs. IMRT (1.6%)
      plans. Daily QA results demonstrated average agreement all three chambers within
      0.4% over 9 month period with no false positives at a 3% threshold. DISCUSSION:
      The methodology described is simple in design and characterizes both the inherit
      limitations of the measurement system as well at the dose based measurements that
      may be directly related to patient plan QA.

PMID- 23554949
TI  - Characterization of the distal polyadenylation site of the beta-adducin (Add2)
      pre-mRNA.
AB  - Most genes have multiple polyadenylation sites (PAS), which are often selected in
      a tissue-specific manner, altering protein products and affecting mRNA stability,
      subcellular localization and/or translability. Here we studied the
      polyadenylation mechanisms associated to the beta-adducin gene (Add2). We have
      previously shown that the Add2 gene has a very tight regulation of alternative
      polyadenylation, using proximal PAS in erythroid tissues, and a distal one in
      brain. Using chimeric minigenes and cell transfections we identified the core
      elements responsible for polyadenylation at the distal PAS. Deletion of either
      the hexanucleotide motif (Hm) or the downstream element (DSE) resulted in
      reduction of mature mRNA levels and activation of cryptic PAS, suggesting an
      important role for the DSE in polyadenylation of the distal Add2 PAS. Point
      mutation of the UG repeats present in the DSE, located immediately after the
      cleavage site, resulted in a reduction of processed mRNA and in the activation of
      the same cryptic site. RNA-EMSA showed that this region is active in forming RNA
      protein complexes. Competition experiments showed that RNA lacking the DSE was
      not able to compete the RNA-protein complexes, supporting the hypothesis of an
      essential important role for the DSE. Next, using a RNA-pull down approach we
      identified some of the proteins bound to the DSE. Among these proteins we found
      PTB, TDP-43, FBP1 and FBP2, nucleolin, RNA helicase A and vigilin. All these
      proteins have a role in RNA metabolism, but only PTB has a reported function in
      polyadenylation. Additional experiments are needed to determine the precise
      functional role of these proteins in Add2 polyadenylation.

PMID- 23554951
TI  - In vitro inhibition of angiogenesis by antibodies directed against the
      37kDa/67kDa laminin receptor.
AB  - The 37kDa/67kDa laminin receptor (LRP/LR) is a central receptor mediating
      interactions between tumour cells and the basement membrane and is thereby a key
      player in adhesion and invasion, essential processes in metastatic cancer. To
      affect continued tumour growth, tumours induce angiogenesis for the constant
      delivery of nutrients and oxygen. This study aims to determine the blocking
      effect of the anti-LRP/LR specific antibody, W3 on the angiogenic potential of
      HUVE (human umbilical vein endothelial) cells. Flow cytometric analysis revealed
      that 97% of HUVE cells display cell surface LRP/LR. An angiogenesis assay was
      conducted employing HUVE cells seeded on the basement membrane reconstituent
      MatrigelTM supplemented with the pro-angiogenic factor vascular endothelial
      growth factor (VEGF). Post 18h incubation at 37 degrees C tubular structures,
      namely tube lengths were assessed. Treatment of established tubular structures
      with 100 ug/ml anti-LRP/LR specific antibody completely blocked angiogenesis. Our
      findings suggest a central role of the 37kDa/67kDa LRP/LR in tube formation and
      recommends anti-LRP/LR specific antibodies as potential therapeutic tools for
      treatment of tumour angiogenesis.

PMID- 23554950
TI  - Somatosensory abnormalities for painful and innocuous stimuli at the back and at
      a site distinct from the region of pain in chronic back pain patients.
AB  - Chronic low back pain (CLBP) was shown to be associated with pathophysiological
      changes at several levels of the sensorimotor system. Changes in sensory
      thresholds have been reported but complete profiles of Quantitative Sensory
      Testing (QST) were only rarely obtained in CLBP patients. The aim of the present
      study was to investigate comprehensive QST profiles in CLBP at the painful site
      (back) and at a site distinct from their painful region (hand) and to compare
      these data with similar data in healthy controls. We found increased detection
      thresholds in CLBP patients compared to healthy controls for all innocuous
      stimuli at the back and extraterritorial to the painful region at the hand.
      Additionally, CLBP patients showed decreased pain thresholds at both sites.
      Importantly, there was no interaction between the investigated site and group,
      i.e. thresholds were changed both at the affected body site and for the site
      distinct from the painful region (hand). Our results demonstrate severe,
      widespread changes in somatosensory sensitivity in CLBP patients. These
      widespread changes point to alterations at higher levels of the neuraxis or/and
      to a vulnerability to nociceptive plasticity in CLBP patients.

PMID- 23554952
TI  - Insect odorant response sensitivity is tuned by metabotropically autoregulated
      olfactory receptors.
AB  - Insects possess one of the most exquisitely sensitive olfactory systems in the
      animal kingdom, consisting of three different types of chemosensory receptors:
      ionotropic glutamate-like receptors (IRs), gustatory receptors (GRs) and odorant
      receptors (ORs). Both insect ORs and IRs are ligand-gated ion channels, but ORs
      possess a unique configuration composed of an odorant-specific protein OrX and a
      ubiquitous coreceptor (Orco). In addition, these two ionotropic receptors confer
      different tuning properties for the neurons in which they are expressed. Unlike
      IRs, neurons expressing ORs are more sensitive and can also be sensitized by sub
      threshold concentrations of stimuli. What is the mechanistic basis for these
      differences in tuning? We show that intrinsic regulation of Orco enhances
      neuronal response to odorants and sensitizes the ORs. We also demonstrate that
      inhibition of metabotropic regulation prevents receptor sensitization. Our
      results indicate that Orco-mediated regulation of OR sensitivity provides tunable
      ionotropic receptors capable of detecting odors over a wider range of
      concentrations, providing broadened sensitivity over IRs themselves.

PMID- 23554953
TI  - The contribution of ArsB to arsenic resistance in Campylobacter jejuni.
AB  - Arsenic, a toxic metalloid, exists in the natural environment and its organic
      form is approved for use as a feed additive for animal production. As a major
      foodborne pathogen of animal origin, Campylobacter is exposed to arsenic
      selection pressure in the food animal production environments. Previous studies
      showed that Campylobacter isolates from poultry were highly resistant to arsenic
      compounds and a 4-gene operon (containing arsP, arsR, arsC, and acr3) was
      associated with arsenic resistance in Campylobacter. However, this 4-gene operon
      is only present in some Campylobacter isolates and other arsenic resistance
      mechanisms in C. jejuni have not been characterized. In this study, we determined
      the role of several putative arsenic resistance genes including arsB, arsC2, and
      arsR3 in arsenic resistance in C. jejuni and found that arsB, but not the other
      two genes, contributes to the resistance to arsenite and arsenate. Inactivation
      of arsB in C. jejuni resulted in 8- and 4-fold reduction in the MICs of arsenite
      and arsenate, respectively, and complementation of the arsB mutant restored the
      MIC of arsenite. Additionally, overexpression of arsB in C. jejuni 11168 resulted
      in a 16-fold increase in the MIC of arsenite. PCR analysis of C. jejuni isolates
      from different animals hosts indicated that arsB and acr3 (the 4-gene operon) are
      widely distributed in various C. jejuni strains, suggesting that Campylobacter
      requires at least one of the two genes for adaptation to arsenic-containing
      environments. These results identify ArsB as an alternative mechanism for arsenic
      resistance in C. jejuni and provide new insights into the adaptive mechanisms of
      Campylobacter in animal food production environments.

PMID- 23554954
TI  - MMP-sensitive PEG diacrylate hydrogels with spatial variations in matrix
      properties stimulate directional vascular sprout formation.
AB  - The spatial presentation of immobilized extracellular matrix (ECM) cues and
      matrix mechanical properties play an important role in directed and guided cell
      behavior and neovascularization. The goal of this work was to explore whether
      gradients of elastic modulus, immobilized matrix metalloproteinase (MMP)
      sensitivity, and YRGDS cell adhesion ligands are capable of directing 3D vascular
      sprout formation in tissue engineered scaffolds. PEGDA hydrogels were engineered
      with mechanical and biofunctional gradients using perfusion-based frontal
      photopolymerization (PBFP). Bulk photopolymerized hydrogels with uniform
      mechanical properties, degradation, and immobilized biofunctionality served as
      controls. Gradient hydrogels exhibited an 80.4% decrease in elastic modulus and a
      56.2% decrease in immobilized YRGDS. PBFP hydrogels also demonstrated gradients
      in hydrogel degradation with degradation times ranging from 10-12 hours in the
      more crosslinked regions to 4-6 hours in less crosslinked regions. An in vitro
      model of neovascularization, composed of co-culture aggregates of endothelial and
      smooth muscle cells, was used to evaluate the effect of these gradients on
      vascular sprout formation. Aggregate invasion in gradient hydrogels occurred bi
      directionally with sprout alignment observed in the direction parallel to the
      gradient while control hydrogels with homogeneous properties resulted in uniform
      invasion. In PBFP gradient hydrogels, aggregate sprout length was found to be
      twice as long in the direction parallel to the gradient as compared to the
      perpendicular direction after three weeks in culture. This directionality was
      found to be more prominent in gradient regions of increased stiffness,
      crosslinked MMP-sensitive peptide presentation, and immobilized YRGDS
      concentration.

PMID- 23554955
TI  - An online database of infant functional near infrared spectroscopy studies: a
      community-augmented systematic review.
AB  - Until recently, imaging the infant brain was very challenging. Functional Near
      InfraRed Spectroscopy (fNIRS) is a promising, relatively novel technique, whose
      use is rapidly expanding. As an emergent field, it is particularly important to
      share methodological knowledge to ensure replicable and robust results. In this
      paper, we present a community-augmented database which will facilitate precisely
      this exchange. We tabulated articles and theses reporting empirical fNIRS
      research carried out on infants below three years of age along several
      methodological variables. The resulting spreadsheet has been uploaded in a format
      allowing individuals to continue adding new results, and download the most recent
      version of the table. Thus, this database is ideal to carry out systematic
      reviews. We illustrate its academic utility by focusing on the factors affecting
      three key variables: infant attrition, the reliability of oxygenated and
      deoxygenated responses, and signal-to-noise ratios. We then discuss strengths and
      weaknesses of the DBIfNIRS, and conclude by suggesting a set of simple guidelines
      aimed to facilitate methodological convergence through the standardization of
      reports.

PMID- 23554956
TI  - Brap2 regulates temporal control of NF-kappaB localization mediated by
      inflammatory response.
AB  - Nuclear factor-kappaB (NF-kappaB) is critical for the expression of multiple
      genes involved in inflammatory responses and cellular survival. NF-kappaB is
      normally sequestered in the cytoplasm through interaction with an inhibitor of NF
      kappaB (IkappaB), but inflammatory stimulation induces proteasomal degradation of
      IkappaB, followed by NF-kappaB nuclear translocation. The degradation of IkappaB
      is mediated by a SCF (Skp1-Cullin1-F-box protein)-type ubiquitin ligase complex
      that is post-translationaly modified by a ubiquitin-like molecule Nedd8. In this
      study, we report that BRCA1-associated protein 2 (Brap2) is a novel Nedd8-binding
      protein that interacts with SCF complex, and is involved in NF-kappaB
      translocation following TNF-alpha stimulation. We also found a putative
      neddylation site in Brap2 associated with NF-kappaB activity. Our findings
      suggest that Brap2 is a novel modulator that associates with SCF complex and
      controls TNF-alpha-induced NF-kappaB nuclear translocation.

PMID- 23554957
TI  - Signatures of demography and recombination at coding genes in naturally
      distributed populations of Arabidopsis lyrata subsp. petraea.
AB  - Demography impacts the observed standing level of genetic diversity present in
      populations. Distinguishing the relative impacts of demography from selection
      requires a baseline of expressed gene variation in naturally occurring
      populations. Six nuclear genes were sequenced to estimate the patterns and levels
      of genetic diversity in natural Arabidopsis lyrata subsp. petraea populations
      that differ in demographic histories since the Pleistocene. As expected, northern
      European populations have genetic signatures of a strong population bottleneck
      likely due to glaciation during the Pleistocene. Levels of diversity in the
      northern populations are about half of that in central European populations.
      Bayesian estimates of historical population size changes indicate that central
      European populations also have signatures of population size change since the
      last glacial maxima, suggesting that these populations are not as stable as
      previously thought. Time since divergence amongst northern European populations
      is higher than amongst central European populations, suggesting that the northern
      European populations were established before the Pleistocene and survived
      glaciation in small separated refugia. Estimates of demography based on expressed
      genes are complementary to estimates based on microsatellites and transposable
      elements, elucidating temporal shifts in population dynamics and confirming the
      importance of marker selection for tests of demography.

PMID- 23554958
TI  - Ideal cardiovascular health metrics on the prevalence of asymptomatic
      intracranial artery stenosis: a cross-sectional study.
AB  - BACKGROUND AND PURPOSE: Intracranial Artery Stenosis (ICAS) is one of the most
      common causes of ischemic stroke in Asia. Previous studies have shown the number
      of ideal cardiovascular health (CVH) metrics was associated with lower risk of
      stroke. This study aimed to investigate the relationship between ideal CVH
      metrics and prevalence of ICAS. METHODS: A random sample of 5,412 participants
      (selected from Kailuan Study as a reference population) aged 40 years or older
      (40.10% women), free of stroke, transient ischemic attack, and coronary disease,
      were enrolled in the Asymptomatic Polyvascular Abnormalities Community study from
      2010 to 2011. We collected information on the seven CVH metrics (including
      smoking, body mass index, dietary intake, physical activity, blood pressure,
      total cholesterol and fasting blood glucose); and assessed ICAS by transcranial
      Doppler. The relationship between the ideal CVH metrics and prevalence of ICAS
      was analyzed using the multivariate logistic regression. RESULTS: After adjusting
      for age, sex, and other potential confounders, the adjusted odds ratios(95%
      confidence interval) for ICAS were 0.76(0.58-0.99), 0.55(0.43-0.72), 0.49(0.37
      0.65), 0.43(0.31-0.61), and 0.36(0.22-0.62), respectively, for those having 2, 3,
      4, 5, and 6-7 ideal CVH metrics compared with those having 0-1 ideal metric(p
      trend<0.0001). Similar inverse associations were observed in different age and
      gender groups (all p-trends<0.05). CONCLUSION: We found a clear gradient
      relationship between the number of ideal CVH metrics and lower prevalence of ICAS
      in a Chinese population, which supports the importance of ideal health behaviors
      and factors in the prevention of ICAS.

PMID- 23554959
TI  - Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.
AB  - Genistein has been shown to inhibit cancers both in vitro and in vivo, by
      altering the expression of several microRNAs (miRNAs). In this study, we focused
      on tumor suppressor miRNAs regulated by genistein and investigated their function
      in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and
      real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in
      PCa cells treated with genistein compared with vehicle control. The expression of
      miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues
      compared with normal prostate cells (RWPE-1) and adjacent normal tissues. Low
      expression level of miR-574-3p was correlated with advanced tumor stage and
      higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells
      significantly inhibited cell proliferation, migration and invasion in vitro and
      in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and
      activating caspase-9 and caspase-3. Using GeneCodis software analysis, several
      pathways affected by miR-574-3p were identified, such as 'Pathways in cancer',
      'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter
      assays demonstrated that miR-574-3p directly binds to the 3' UTR of several
      target genes (such as RAC1, EGFR and EP300) that are components of 'Pathways in
      cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and
      protein expression levels of the three target genes in PCa cells were markedly
      down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the
      three target genes significantly affect cell proliferation, migration and
      invasion in PCa cell lines. Our results show that genistein up-regulates tumor
      suppressor miR-574-3p expression targeting several cell signaling pathways. These
      findings enhance understanding of how genistein regulates with miRNA in PCa.

PMID- 23554961
TI  - Limits of [18F]-FLT PET as a biomarker of proliferation in oncology.
AB  - BACKGROUND: Non-invasive imaging biomarkers of cellular proliferation hold great
      promise for quantifying response to personalized medicine in oncology. An
      emerging approach to assess tumor proliferation utilizes the positron emission
      tomography (PET) tracer 3'-deoxy-3'[(18)F]-fluorothymidine, [(18)F]-FLT. Though
      several studies have associated serial changes in [(18)F]-FLT-PET with elements
      of therapeutic response, the degree to which [(18)F]-FLT-PET quantitatively
      reflects proliferative index has been continuously debated for more that a
      decade. The goal of this study was to elucidate quantitative relationships
      between [(18)F]-FLT-PET and cellular metrics of proliferation in treatment naive
      human cell line xenografts commonly employed in cancer research. METHODS AND
      FINDINGS: [(18)F]-FLT-PET was conducted in human cancer xenograft-bearing mice.
      Quantitative relationships between PET, thymidine kinase 1 (TK1) protein levels
      and immunostaining for proliferation markers (Ki67, TK1, PCNA) were evaluated
      using imaging-matched tumor specimens. Overall, we determined that [(18)F]-FLT
      PET reflects TK1 protein levels, yet the cell cycle specificity of TK1 expression
      and the extent to which tumors utilize thymidine salvage for DNA synthesis
      decouple [(18)F]-FLT-PET data from standard estimates of proliferative index.
      CONCLUSIONS: Our findings illustrate that [(18)F]-FLT-PET reflects tumor
      proliferation as a function of thymidine salvage pathway utilization. Unlike more
      general proliferation markers, such as Ki67, [(18)F]-FLT PET reflects
      proliferative indices to variable and potentially unreliable extents. [(18)F]-FLT
      PET cannot discriminate moderately proliferative, thymidine salvage-driven tumors
      from those of high proliferative index that rely primarily upon de novo thymidine
      synthesis. Accordingly, the magnitude of [(18)F]-FLT uptake should not be
      considered a surrogate of proliferative index. These data rationalize the
      diversity of [(18)F]-FLT-PET correlative results previously reported and suggest
      future best-practices when [(18)F]-FLT-PET is employed in oncology.

PMID- 23554960
TI  - Bronchodilator responsiveness and reported respiratory symptoms in an adult
      population.
AB  - BACKGROUND: The relationship between patient-reported symptoms and objective
      measures of lung function is poorly understood. AIM: To determine the association
      between responsiveness to bronchodilator and respiratory symptoms in random
      population samples. METHODS: 4669 people aged 40 years and older from 8 sites in
      Canada completed interviewer-administered respiratory questionnaires and
      performed spirometry before and after administration of 200 ug of inhaled
      salbutamol. The effect of anthropometric variables, smoking exposure and doctor
      diagnosed asthma (DDA) on bronchodilator responsiveness in forced expiratory
      volume in 1 second (FEV1) and in forced vital capacity (FVC) were evaluated.
      Multiple logistic regression was used to test for association between quintiles
      of increasing changes in FEV1 and in FVC after bronchodilator and several
      respiratory symptoms. RESULTS: Determinants of bronchodilator change in FEV1 and
      FVC included age, DDA, smoking, respiratory drug use and female gender [p<0.005
      to p<0.0001 ]. In subjects without doctor-diagnosed asthma or COPD,
      bronchodilator response in FEV1 was associated with wheezing [p for
      trend<0.0001], while bronchodilator response for FVC was associated with
      breathlessness. [p for trend <0.0001]. CONCLUSIONS: Bronchodilator responsiveness
      in FEV1 or FVC are associated with different respiratory symptoms in the
      community. Both flow and volume bronchodilator responses are useful parameters
      which together can be predictive of both wheezing and breathlessness in the
      general population.

PMID- 23554962
TI  - A novel synthetic microtubule inhibitor, MPT0B214 exhibits antitumor activity in
      human tumor cells through mitochondria-dependent intrinsic pathway.
AB  - Agents that interfere with mitotic progression by disturbing microtubule dynamics
      are commonly used for cancer treatment. Previously, a series of aroylquinolone
      regioisomers as novel microtubule inhibitors were discovered. One of these new
      compounds, MPT0B214 inhibited tubulin polymerization through strongly binding to
      the tubulin's colchicine-binding site and had cytotoxic activity in a variety of
      human tumor cell lines. After treatment with MPT0B214, KB cells were arrested in
      the G2-M phase before cell death occurred, which were associated with
      upregulation of cyclin B1, dephosphorylation of Cdc2, phosphorylation of Cdc25C
      and elevated expression of the mitotic marker MPM-2. Furthermore, the compound
      induced apoptotic cell death through mitochondria/caspase 9-dependent pathway.
      Notably, several KB-derived multidrug-resistant cancer cell lines were also
      sensitive to MPT0B214 treatment. These findings showed that MPT0B214 is a
      potential compound in the treatment of various malignancies.

PMID- 23554963
TI  - Mineral deposition in bacteria-filled and bacteria-free calcium bodies in the
      crustacean Hyloniscus riparius (Isopoda: Oniscidea).
AB  - Crustacean calcium bodies are epithelial sacs which contain a mineralized matrix.
      The objectives of this study were to describe the microscopic anatomy of calcium
      bodies in the terrestrial isopod Hyloniscus riparius and to establish whether
      they undergo molt-related structural changes. We performed 3D reconstruction of
      the calcium bodies from paraffin sections and analyzed their structure with light
      and electron microscopy. In addition, we analyzed the chemical composition of
      their mineralized matrices with micro-Raman spectroscopy. Two pairs of these
      organs are present in H. riparius. One pair is filled with bacteria while the
      other pair is not. In non-molting animals, the bacteria-filled calcium bodies
      contain apatite crystals and the bacteria-free calcium bodies enclose CaCO3
      containing concretions with little organic matrix. During preparation for molt,
      an additional matrix layer is deposited in both pairs of calcium bodies. In the
      bacteria-filled calcium bodies it contains a mixture of calcium carbonate and
      calcium phosphate, whereas only calcium carbonate is present in bacteria-free
      calcium bodies. After ecdysis, all mineral components in bacteria-free calcium
      bodies and the additional matrix layer in bacteria-filled calcium bodies are
      completely resorbed. During calcium resorption, the apical surface of the calcium
      body epithelium is deeply folded and electron dense granules are present in
      spaces between epithelial cells. Our results indicate that the presence of
      bacteria might be linked to calcium phosphate mineralization. Calcium bodies
      likely provide a source of calcium and potentially phosphate for the
      mineralization of the new cuticle after molt. Unlike other terrestrial isopods,
      H. riparius does not form sternal CaCO3 deposits and the bacteria-free calcium
      bodies might functionally replace them in this species.

PMID- 23554965
TI  - Small-scale habitat structure modulates the effects of no-take marine reserves
      for coral reef macroinvertebrates.
AB  - No-take marine reserves are one of the oldest and most versatile tools used
      across the Pacific for the conservation of reef resources, in particular for
      invertebrates traditionally targeted by local fishers. Assessing their actual
      efficiency is still a challenge in complex ecosystems such as coral reefs, where
      reserve effects are likely to be obscured by high levels of environmental
      variability. The goal of this study was to investigate the potential interference
      of small-scale habitat structure on the efficiency of reserves. The spatial
      distribution of widely harvested macroinvertebrates was surveyed in a large set
      of protected vs. unprotected stations from eleven reefs located in New Caledonia.
      Abundance, density and individual size data were collected along random, small
      scale (20*1 m) transects. Fine habitat typology was derived with a quantitative
      photographic method using 17 local habitat variables. Marine reserves
      substantially augmented the local density, size structure and biomass of the
      target species. Density of Trochus niloticus and Tridacna maxima doubled globally
      inside the reserve network; average size was greater by 10 to 20% for T.
      niloticus. We demonstrated that the apparent success of protection could be
      obscured by marked variations in population structure occurring over short
      distances, resulting from small-scale heterogeneity in the reef habitat. The
      efficiency of reserves appeared to be modulated by the availability of suitable
      habitats at the decimetric scale ("microhabitats") for the considered sessile/low
      mobile macroinvertebrate species. Incorporating microhabitat distribution could
      significantly enhance the efficiency of habitat surrogacy, a valuable approach in
      the case of conservation targets focusing on endangered or emblematic
      macroinvertebrate or relatively sedentary fish species.

PMID- 23554964
TI  - Historical shifts in Brazilian P. falciparum population structure and drug
      resistance alleles.
AB  - Previous work suggests that Brazilian Plasmodium falciparum has limited genetic
      diversity and a history of bottlenecks, multiple reintroductions due to human
      migration, and clonal expansions. We hypothesized that Brazilian P. falciparum
      would exhibit clonal structure. We examined isolates collected across two decades
      from Amapa, Rondonia, and Para state (n = 190). By examining more microsatellites
      markers on more chromosomes than previous studies, we hoped to define the extent
      of low diversity, linkage disequilibrium, bottlenecks, population structure, and
      parasite migration within Brazil. We used retrospective genotyping of samples
      from the 1980s and 1990s to explore the population genetics of SP resistant dhfr
      and dhps alleles. We tested an existing hypothesis that the triple mutant dhfr
      mutations 50R/51I/108N and 51I/108N/164L developed in southern Amazon from a
      single origin of common or similar parasites. We found that Brazilian P.
      falciparum had limited genetic diversity and isolation by distance was rejected,
      which suggests it underwent bottlenecks followed by migration between sites.
      Unlike Peru, there appeared to be gene flow across the Brazilian Amazon basin. We
      were unable to divide parasite populations by clonal lineages and pairwise FST
      were common. Most parasite diversity was found within sites in the Brazilian
      Amazon, according to AMOVA. Our results challenge the hypothesis that triple
      mutant alleles arose from a single lineage in the Southern Amazon. SP resistance,
      at both the double and triple mutant stages, developed twice and potentially in
      different regions of the Brazilian Amazon. We would have required samples from
      before the 1980s to describe how SP resistance spread across the basin or
      describe the complex internal migration of Brazilian parasites after the
      colonization efforts of past decades. The Brazilian Amazon basin may have
      sufficient internal migration for drug resistance reported in any particular
      region to rapidly spread to other parts of basin under similar drug pressure.

PMID- 23554966
TI  - FlgM as a secretion moiety for the development of an inducible type III secretion
      system.
AB  - Regulation and assembly of the flagellar type III secretion system is one of the
      most investigated and best understood regulational cascades in molecular biology.
      Depending on the host organism, flagellar morphogenesis requires the interplay of
      more than 50 genes. Direct secretion of heterologous proteins to the supernatant
      is appealing due to protection against cellular proteases and simplified
      downstream processing. As Escherichia coli currently remains the predominant host
      organism used for recombinant prokaryotic protein expression, the generation of a
      strain that exhibits inducible flagellar secretion would be highly desirable for
      biotechnological applications. Here, we report the first engineered Escherichia
      coli mutant strain featuring flagellar morphogenesis upon addition of an external
      inducer. Using FlgM as a sensor for direct secretion in combination with this
      novel strain may represent a potent tool for significant improvements in future
      engineering of an inducible type III secretion for heterologous proteins.

PMID- 23554967
TI  - Reduced ventral cingulum integrity and increased behavioral problems in children
      with isolated optic nerve hypoplasia and mild to moderate or no visual
      impairment.
AB  - OBJECTIVES: To assess the prevalence of behavioral problems in children with
      isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no
      developmental delay. To identify white matter abnormalities that may provide
      neural correlates for any behavioral abnormalities identified. PATIENTS AND
      METHODS: Eleven children with isolated optic nerve hypoplasia (mean age 5.9
      years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty
      four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11
      of whom also completed behavioral assessments. Fractional anisotropy images were
      processed using tract-based spatial statistics. Partial correlation between
      ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and
      child behavioral checklist scores (controlled for age at scan and sex) was
      performed. RESULTS: Children with optic nerve hypoplasia had significantly higher
      scores on the child behavioral checklist (p<0.05) than controls (4 had scores in
      the clinically significant range). Ventral cingulum, corpus callosum and optic
      radiation fractional anisotropy were significantly reduced in children with optic
      nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with
      total and externalising child behavioral checklist scores (r = -0.52, p<0.02, r =
      -0.46, p<0.049 respectively). There were no significant correlations between left
      ventral cingulum, corpus callosum or optic radiation fractional anisotropy and
      behavioral scores. CONCLUSIONS: Our findings suggest that children with optic
      nerve hypoplasia and mild to moderate or no visual impairment require behavioral
      assessment to determine the presence of clinically significant behavioral
      problems. Reduced structural integrity of the ventral cingulum correlated with
      behavioral scores, suggesting that these white matter abnormalities may be
      clinically significant. The presence of reduced fractional anisotropy in the
      optic radiations of children with mild to moderate or no visual impairment raises
      questions as to the pathogenesis of these changes which will need to be addressed
      by future studies.

PMID- 23554968
TI  - Novel association between plasma matrix metalloproteinase-9 and risk of incident
      atrial fibrillation in a case-cohort study: the Atherosclerosis Risk in
      Communities study.
AB  - BACKGROUND: Previous cross-sectional studies have suggested that biomarkers of
      extracellular matrix remodelling are associated with atrial fibrillation (AF),
      but no prospective data have yet been published. Hence, we examine whether plasma
      matrix metalloproteinases (MMP) and their inhibitors are related to increased
      risk of incident AF. METHODS: We used a case-cohort design in the context of the
      prospective Atherosclerosis Risk in Communities (ARIC) study. From 13718 eligible
      men and women free from AF in 1990-92, we selected a stratified random sample of
      500 individuals without and 580 with incident AF over a mean follow-up of 11.8
      years. Using a weighted proportional hazards regression model, the relationships
      between MMP-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)
      1, TIMP-2 and C-terminal propeptide of collagen type-I with incident AF were
      examined after adjusting for confounders. RESULTS: In models adjusted for age,
      sex and race, all biomarkers were associated with AF, but only the relationship
      between plasma MMP-9 remained significant in the fully-adjusted model: each one
      standard deviation increase in MMP-9 was associated with 27% (95% Confidence
      Interval: 7% to 50%) increase in risk of AF with no evidence of an interaction
      with race or sex. Individuals with above mean levels of MMP-9 were more likely to
      be male, white and current smokers. CONCLUSIONS: The findings suggest that
      elevated levels of MMP-9 are independently associated with increased risk of AF.
      However, given the lack of specificity of MMP-9 to atrial tissue, it remains to
      be determined whether the observed relationship reflects the impact of atrial
      fibrosis or more generalized fibrosis on risk of incident AF.

PMID- 23554969
TI  - Genome-wide analysis using exon arrays demonstrates an important role for
      expression of extra-cellular matrix, fibrotic control and tissue remodelling
      genes in Dupuytren's disease.
AB  - Dupuytren's disease (DD) is a classic example of pathological fibrosis which
      results in a debilitating disorder affecting a large sector of the human
      population. It is characterized by excessive local proliferation of fibroblasts
      and over-production of collagen and other components of extracellular matrix
      (ECM) in the palmar fascia. The fibrosis progressively results in contracture of
      elements between the palmar fascia and skin causing flexion deformity or clawing
      of the fingers and a severe reduction in hand function. While much is known about
      the pathogenesis and surgical treatment of DD, little is known about the factors
      that cause its onset and progression, despite many years of research. Gene
      expression patterns in DD patients now offers the potential to identify genes
      that direct the pathogenesis of DD. In this study we used primary cultures of
      fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients
      to compare the gene expression profiles on a genome-wide basis with normal
      control fibroblasts. Our investigations have identified genes that may be
      involved with DD pathogenesis including some which are directly relevant to
      fibrosis. In particular, these include significantly reduced expression levels of
      three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and
      significantly increased expression levels of fibroblast growth factors (FGF9,
      FGF11), a number of collagen genes and other ECM genes in DD patient samples.
      Many of these gene products are known to be involved in fibrosis, tumour
      formation and in the normal processes of tissue remodelling. In addition,
      alternative splicing was identified in some DD associated genes. These highly
      sensitive genomic investigations provide new insight into the molecular
      mechanisms that may underpin the development and progression of DD.

PMID- 23554970
TI  - Microorganisms within human follicular fluid: effects on IVF.
AB  - Our previous study reported microorganisms in human follicular fluid. The
      objective of this study was to test human follicular fluid for the presence of
      microorganisms and to correlate these findings with the in vitro fertilization
      (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs
      were collected from women undergoing IVF cycles, with various causes for
      infertility, and were cultured to detect microorganisms. The cause of infertility
      and the IVF outcomes for each woman were correlated with the microorganisms
      detected within follicular fluid collected at the time of trans-vaginal oocyte
      retrieval. Microorganisms isolated from follicular fluids were classified as: (1)
      'colonizers' if microorganisms were detected within the follicular fluid, but not
      within the vaginal swab (at the time of oocyte retrieval); or (2) 'contaminants'
      if microorganisms detected in the vagina at the time of oocyte retrieval were
      also detected within the follicular fluid. The presence of Lactobacillus spp. in
      ovarian follicular fluids was associated with embryo maturation and transfer.
      This study revealed microorganisms in follicular fluid itself and that the
      presence of particular microorganisms has an adverse affect on IVF outcomes as
      seen by an overall decrease in embryo transfer rates and pregnancy rates in both
      fertile and infertile women, and live birth rates in women with idiopathic
      infertility. Follicular fluid microorganisms are a potential cause of adverse
      pregnancy outcomes in IVF in both infertile women and in fertile women with
      infertile male partners.

PMID- 23554971
TI  - Quality evaluation of methyl binding domain based kits for enrichment DNA
      methylation sequencing.
AB  - DNA-methylation is an important epigenetic feature in health and disease.
      Methylated sequence capturing by Methyl Binding Domain (MBD) based enrichment
      followed by second-generation sequencing provides the best combination of
      sensitivity and cost-efficiency for genome-wide DNA-methylation profiling.
      However, existing implementations are numerous, and quality control and
      optimization require expensive external validation. Therefore, this study has two
      aims: 1) to identify a best performing kit for MBD-based enrichment using
      independent validation data, and 2) to evaluate whether quality evaluation can
      also be performed solely based on the characteristics of the generated sequences.
      Five commercially available kits for MBD enrichment were combined with Illumina
      GAIIx sequencing for three cell lines (HCT15, DU145, PC3). Reduced representation
      bisulfite sequencing data (all three cell lines) and publicly available Illumina
      Infinium BeadChip data (DU145 and PC3) were used for benchmarking. Consistent
      large-scale differences in yield, sensitivity and specificity between the
      different kits could be identified, with Diagenode's MethylCap kit as overall
      best performing kit under the tested conditions. This kit could also be
      identified with the Fragment CpG-plot, which summarizes the CpG content of the
      captured fragments, implying that the latter can be used as a tool to monitor
      data quality. In conclusion, there are major quality differences between kits for
      MBD-based capturing of methylated DNA, with the MethylCap kit performing best
      under the used settings. The Fragment CpG-plot is able to monitor data quality
      based on inherent sequence data characteristics, and is therefore a cost
      efficient tool for experimental optimization, but also to monitor quality
      throughout routine applications.

PMID- 23554972
TI  - MYCN transgenic zebrafish model with the characterization of acute myeloid
      leukemia and altered hematopoiesis.
AB  - BACKGROUND: Amplification of MYCN (N-Myc) oncogene has been reported as a
      frequent event and a poor prognostic marker in human acute myeloid leukemia
      (AML). The molecular mechanisms and transcriptional networks by which MYCN exerts
      its influence in AML are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We
      introduced murine MYCN gene into embryonic zebrafish through a heat-shock
      promoter and established the stable germline Tg(MYCN:HSE:EGFP) zebrafish. N-Myc
      downstream regulated gene 1 (NDRG1), negatively controlled by MYCN in human and
      functionally involved in neutrophil maturation, was significantly under-expressed
      in this model. Using peripheral blood smear detection, histological section and
      flow cytometric analysis of single cell suspension from kidney and spleen, we
      found that MYCN overexpression promoted cell proliferation, enhanced the
      repopulating activity of myeloid cells and the accumulation of immature
      hematopoietic blast cells. MYCN enhanced primitive hematopoiesis by upregulating
      scl and lmo2 expression and promoted myelopoiesis by inhibiting gata1 expression
      and inducing pu.1, mpo expression. Microarray analysis identified that cell
      cycle, glycolysis/gluconeogenesis, MAPK/Ras, and p53-mediated apoptosis pathways
      were upregulated. In addition, mismatch repair, transforming and growth factor
      beta (TGFbeta) were downregulated in MYCN-overexpressing blood cells (p<0.01).
      All of these signaling pathways are critical in the proliferation and malignant
      transformation of blood cells. CONCLUSION/SIGNIFICANCE: The above results induced
      by overexpression of MYCN closely resemble the main aspects of human AML,
      suggesting that MYCN plays a role in the etiology of AML. MYCN reprograms
      hematopoietic cell fate by regulating NDRG1 and several lineage-specific
      hematopoietic transcription factors. Therefore, this MYCN transgenic zebrafish
      model facilitates dissection of MYCN-mediated signaling in vivo, and enables high
      throughput scale screens to identify the potential therapeutic targets.

PMID- 23554974
TI  - The effect of age and recent influenza vaccination history on the immunogenicity
      and efficacy of 2009-10 seasonal trivalent inactivated influenza vaccination in
      children.
AB  - BACKGROUND: There is some evidence that annual vaccination of trivalent
      inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity
      but evidence is lacking on whether vaccine efficacy is affected by prior
      vaccination history. The efficacy of one dose of TIV in children 6-8 y of age
      against influenza B is uncertain. We examined whether immunogenicity and efficacy
      of influenza vaccination in school-age children varied by age and past
      vaccination history. METHODS AND FINDINGS: We conducted a randomized controlled
      trial of 2009-10 TIV. Influenza vaccination history in the two preceding years
      was recorded. Immunogenicity was assessed by comparison of HI titers before and
      one month after receipt of TIV/placebo. Subjects were followed up for 11 months
      with symptom diaries, and respiratory specimens were collected during acute
      respiratory illnesses to permit confirmation of influenza virus infections. We
      found that previous vaccination was associated with reduced antibody responses to
      TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9-17 y of age,
      but increased antibody responses to the same lineage of influenza B virus in
      children 6-8 y of age. Serological responses to the influenza A vaccine viruses
      were high regardless of vaccination history. One dose of TIV appeared to be
      efficacious against confirmed influenza B in children 6-8 y of age regardless of
      vaccination history. CONCLUSIONS: Prior vaccination was associated with lower
      antibody titer rises following vaccination against seasonal influenza A vaccine
      viruses, but higher responses to influenza B among individuals primed with
      viruses from the same lineage in preceding years. In a year in which influenza B
      virus predominated, no impact of prior vaccination history was observed on
      vaccine efficacy against influenza B. The strains that circulated in the year of
      study did not allow us to study the effect of prior vaccination on vaccine
      efficacy against influenza A.

PMID- 23554973
TI  - HIV-1 gp120 protein downregulates Nef induced IL-6 release in immature dentritic
      cells through interplay of DC-SIGN.
AB  - HIV-1 replication is a tightly controlled mechanism which demands the interplay
      of host as well as viral factors. Both gp120 (envelope glycoprotein) and Nef
      (regulatory protein) have been correlated with the development of AIDS disease in
      independent studies. In this context, the ability of HIV-1 to utilize immature
      dentritic cells for transfer of virus is pivotal for early pathogenesis. The
      presence of C-type lectins on dendritic cells (DCs) like DC-SIGN, are crucial in
      inducing antiviral immunity to HIV-1. Both gp120 and Nef induce the release of
      cytokines leading to multiple effects of viral pathogenesis. Our study elucidated
      for the first time the cross-talk of the signaling mechanism of these two viral
      proteins in immature monocyte derived dentritic cells (immDCs). Further, gp120
      was found to downregulate the IL-6 release by Nef, depending on the interaction
      with DC-SIGN. A cascade of signaling followed thereafter, including the
      activation of SOCS-3, to mediate the diminishing effect of gp120. Our results
      also revealed that the anti-apoptotic signals emanated from Nef was put to halt
      by gp120 through inhibition of Nef induced STAT3. Thus our results implicate that
      the signaling generated by gp120 and Nef, undergoes a switch-over mechanism that
      significantly contributes to the pathogenesis of HIV-1 and widens our view
      towards the approach on battling the viral infection.

PMID- 23554975
TI  - Horizontal transfer of a subtilisin gene from plants into an ancestor of the
      plant pathogenic fungal genus Colletotrichum.
AB  - The genus Colletotrichum contains a large number of phytopathogenic fungi that
      produce enormous economic losses around the world. The effect of horizontal gene
      transfer (HGT) has not been studied yet in these organisms. Inter-Kingdom HGT
      into fungal genomes has been reported in the past but knowledge about the HGT
      between plants and fungi is particularly limited. We describe a gene in the
      genome of several species of the genus Colletotrichum with a strong resemblance
      to subtilisins typically found in plant genomes. Subtilisins are an important
      group of serine proteases, widely distributed in all of the kingdoms of life. Our
      hypothesis is that the gene was acquired by Colletotrichum spp. through (HGT)
      from plants to a Colletotrichum ancestor. We provide evidence to support this
      hypothesis in the form of phylogenetic analyses as well as a characterization of
      the similarity of the subtilisin at the primary, secondary and tertiary
      structural levels. The remarkable level of structural conservation of
      Colletotrichum plant-like subtilisin (CPLS) with plant subtilisins and the
      differences with the rest of Colletotrichum subtilisins suggests the possibility
      of molecular mimicry. Our phylogenetic analysis indicates that the HGT event
      would have occurred approximately 150-155 million years ago, after the divergence
      of the Colletotrichum lineage from other fungi. Gene expression analysis shows
      that the gene is modulated during the infection of maize by C. graminicola
      suggesting that it has a role in plant disease. Furthermore, the upregulation of
      the CPLS coincides with the downregulation of several plant genes encoding
      subtilisins. Based on the known roles of subtilisins in plant pathogenic fungi
      and the gene expression pattern that we observed, we postulate that the CPLSs
      have an important role in plant infection.

PMID- 23554976
TI  - Visual word recognition in deaf readers: lexicality is modulated by communication
      mode.
AB  - Evidence indicates that adequate phonological abilities are necessary to develop
      proficient reading skills and that later in life phonology also has a role in the
      covert visual word recognition of expert readers. Impairments of acoustic
      perception, such as deafness, can lead to atypical phonological representations
      of written words and letters, which in turn can affect reading proficiency. Here,
      we report an experiment in which young adults with different levels of acoustic
      perception (i.e., hearing and deaf individuals) and different modes of
      communication (i.e., hearing individuals using spoken language, deaf individuals
      with a preference for sign language, and deaf individuals using the oral modality
      with less or no competence in sign language) performed a visual lexical decision
      task, which consisted of categorizing real words and consonant strings. The
      lexicality effect was restricted to deaf signers who responded faster to real
      words than consonant strings, showing over-reliance on whole word lexical
      processing of stimuli. No effect of stimulus type was found in deaf individuals
      using the oral modality or in hearing individuals. Thus, mode of communication
      modulates the lexicality effect. This suggests that learning a sign language
      during development shapes visuo-motor representations of words, which are tuned
      to the actions used to express them (phono-articulatory movements vs. hand
      movements) and to associated perceptions. As these visuo-motor representations
      are elicited during on-line linguistic processing and can overlap with the
      perceptual-motor processes required to execute the task, they can potentially
      produce interference or facilitation effects.

PMID- 23554977
TI  - Fibroblast growth factor 2 induces E-cadherin down-regulation via PI3K/Akt/mTOR
      and MAPK/ERK signaling in ovarian cancer cells.
AB  - Fibroblast growth factor 2 (FGF2) is produced by ovarian cancer cells and it has
      been suggested to play an important role in tumor progression. In this study, we
      report that FGF2 treatment down-regulated E-cadherin by up-regulating its
      transcriptional repressors, Slug and ZEB1, in human ovarian cancer cells. The
      pharmacological inhibition of phosphatidylinositol-3-kinase (PI3K), mammalian
      target of rapamycin (mTOR), and MEK suggests that both PI3K/Akt/mTOR and MAPK/ERK
      signaling are required for FGF2-induced E-cadherin down-regulation. Moreover,
      FGF2 up-regulated Slug and ZEB1 expression via the PI3K/Akt/mTOR and MAPK/ERK
      signaling pathways, respectively. Finally, FGF2-induced cell invasion was
      abolished by the inhibition of the PI3K/Akt/mTOR and MAPK/ERK pathways, and the
      forced expression of E-cadherin diminished the intrinsic invasiveness of ovarian
      cancer cells as well as the FGF2-induced cell invasion. This study demonstrates a
      novel mechanism in which FGF2 down-regulates E-cadherin expression through the
      activation of PI3K/Akt/mTOR and MAPK/ERK signaling, and the up-regulation of Slug
      and ZEB1 in human ovarian cancer cells.

PMID- 23554978
TI  - Association between Facebook dependence and poor sleep quality: a study in a
      sample of undergraduate students in Peru.
AB  - OBJECTIVES: Internet can accelerate information exchange. Social networks are the
      most accessed especially Facebook. This kind of networks might create dependency
      with several negative consequences in people's life. The aim of this study was to
      assess potential association between Facebook dependence and poor sleep quality.
      METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study was performed enrolling
      undergraduate students of the Universidad Peruana de Ciencias Aplicadas, Lima,
      Peru. The Internet Addiction Questionnaire, adapted to the Facebook case, and the
      Pittsburgh Sleep Quality Index, were used. A global score of 6 or greater was
      defined as the cutoff to determine poor sleep quality. Generalized linear model
      were used to determine prevalence ratios (PR) and 95% confidence intervals
      (95%CI). A total of 418 students were analyzed; of them, 322 (77.0%) were women,
      with a mean age of 20.1 (SD: 2.5) years. Facebook dependence was found in 8.6%
      (95% CI: 5.9%-11.3%), whereas poor sleep quality was present in 55.0% (95% CI:
      50.2%-59.8%). A significant association between Facebook dependence and poor
      sleep quality mainly explained by daytime dysfunction was found (PR = 1.31;
      IC95%: 1.04-1.67) after adjusting for age, sex and years in the faculty.
      CONCLUSIONS: There is a relationship between Facebook dependence and poor quality
      of sleep. More than half of students reported poor sleep quality. Strategies to
      moderate the use of this social network and to improve sleep quality in this
      population are needed.

PMID- 23554979
TI  - Proteasome activity influences UV-mediated subnuclear localization changes of
      NPM.
AB  - UV damage activates cellular stress signaling pathways, causes DNA helix
      distortions and inhibits transcription by RNA polymerases I and II. In
      particular, the nucleolus, which is the site of RNA polymerase I transcription
      and ribosome biogenesis, disintegrates following UV damage. The disintegration is
      characterized by reorganization of the subnucleolar structures and change of
      localization of many nucleolar proteins. Here we have queried the basis of
      localization change of nucleophosmin (NPM), a nucleolar granular component
      protein, which is increasingly detected in the nucleoplasm following UV
      radiation. Using photobleaching experiments of NPM-fluorescent fusion protein in
      live human cells we show that NPM mobility increases after UV damage. However, we
      show that the increase in NPM nucleoplasmic abundance after UV is independent of
      UV-activated cellular stress and DNA damage signaling pathways. Unexpectedly, we
      find that proteasome activity affects NPM redistribution. NPM nucleolar
      expression was maintained when the UV-treated cells were exposed to proteasome
      inhibitors or when the expression of proteasome subunits was inhibited using
      RNAi. However, there was no evidence of increased NPM turnover in the UV damaged
      cells, or that ubiquitin or ubiquitin recycling affected NPM localization. These
      findings suggest that proteasome activity couples to nucleolar protein
      localizations in UV damage stress.

PMID- 23554981
TI  - Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in
      Bbs4 null mice.
AB  - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive
      disorder characterized by obesity, retinal degeneration, polydactyly,
      hypogenitalism and renal defects. Recent findings have associated the etiology of
      the disease with cilia, and BBS proteins have been implicated in trafficking
      various ciliary cargo proteins. To date, 17 different genes have been reported
      for BBS among which BBS1 is the most common cause of the disease followed by
      BBS10, and BBS4. A murine model of Bbs4 is known to phenocopy most of the human
      BBS phenotypes, and it is being used as a BBS disease model. To better understand
      the in vivo localization, cellular function, and interaction of BBS4 with other
      proteins, we generated a transgenic BBS4 mouse expressing the human BBS4 gene
      under control of the beta actin promoter. The transgene is expressed in various
      tissues including brain, eye, testis, heart, kidney, and adipose tissue. These
      mice were further bred to express the transgene in Bbs4 null mice, and their
      phenotype was characterized. Here we report that despite tissue specific variable
      expression of the transgene, human BBS4 was able to complement the deficiency of
      Bbs4 and rescue all the BBS phenotypes in the Bbs4 null mice. These results
      provide an encouraging prospective for gene therapy for BBS related phenotypes
      and potentially for other ciliopathies.

PMID- 23554980
TI  - Use of primary care during the year before childhood cancer diagnosis: a
      nationwide population-based matched comparative study.
AB  - OBJECTIVE: Childhood cancer is rare and symptoms tend to be unspecific and vague.
      Using the utilization of health care services as a proxy for symptoms, the
      present study seeks to determine when early symptoms of childhood cancer are seen
      in general practice. METHODS: A population-based matched comparative study was
      conducted using nationwide registry data. As cases, all children in Denmark below
      16 years of age (N = 1,278) diagnosed with cancer (Jan 2002-Dec 2008) were
      included. As controls, 10 children per case matched on gender and date of birth
      (N = 12,780) were randomly selected. The utilization of primary health care
      services (daytime contacts, out-of-hours contacts and diagnostic procedures)
      during the year preceding diagnosis/index date was measured for cases and
      controls. RESULTS: During the six months before diagnosis, children with cancer
      used primary care more than the control cohort. This excess use grew consistently
      and steadily towards the time of diagnosis with an IRR = 3.19 (95%CI: 2.99-3.39)
      (p<0.0001) during the last three months before diagnosis. Children with Central
      Nervous System (CNS) tumours had more contacts than other children during the
      entire study period. The use of practice-based diagnostic tests and the number of
      out-of-hours contacts began to increase four to five months before cancer
      diagnosis. CONCLUSIONS: The study shows that excess health care use, a proxy for
      symptoms of childhood cancer, occurs months before the diagnosis is established.
      Children with lymphoma, bone tumour or other solid tumours had higher
      consultation rates than the controls in the last five months before diagnosis,
      whereas children with CNS tumour had higher consultation rates in all twelve
      months before diagnosis. More knowledge about early symptoms and the diagnostic
      pathway for childhood cancer would be clinically relevant.

PMID- 23554982
TI  - IOL tilt and decentration estimation from 3 dimensional reconstruction of OCT
      image.
AB  - PURPOSE: To evaluate intraocular lens (IOL) tilt and decentration by anterior
      segment optical coherence tomography (AS-OCT) using 3-dimensional (3D)
      reconstruction method. DESIGN: Prospective observational case series.
      PARTICIPANTS: Thirty-nine patients (39 eyes) were included. METHODS: The IOL
      positions of all eyes were examined by AS-OCT. Images were obtained in 4 axes (0
      180 degrees, 45-225 degrees, 90-270 degrees, and 135-315 degrees) using the
      quadrant-scan model. The cross-sectional images were analyzed with MATLAB
      software. MAIN OUTCOME MEASURES: The angle (theta) between the reference
      pupillary plane and the IOL plane, the distances between the center points of the
      pupil circle and the IOL on the x-axis (dx) and y-axis (dy) and the spatial
      distance (ds) were calculated after 3D-reconstruction. RESULTS: The mean angle
      (theta) between the pupillary plane and the IOL plane was 2.94+/-0.99 degrees.
      The mean IOL decentration of dx and dy was 0.32+/-0.26 mm and 0.40+/-0.27 mm,
      respectively. The ds of the IOL decentration was 0.56+/-0.31 mm. There was no
      significant correlation between the ocular residual astigmatism (ORA) and the
      tilted angle or the decentration distance. There was a significant correlation
      between the ORA and total astigmatism (r = 0.742, P<0.001). There was no
      significant correlation between the postoperative best corrected visual acuity
      (BCVA) and the ORA (r = 0.156; P = 0.344), total astigmatism (r = 0.012; P =
      0.942), tilted angle (theta; r = 0.172; P = 0.295) or decentration distance (dx:
      r = 0.191, P = 0.244; dy: r = 0.253, P = 0.121; ds: r = 0.298, P = 0.065).
      CONCLUSIONS: AS-OCT can be used as an alternative for the analysis of IOL tilt
      and decentration using 3D-reconstruction.

PMID- 23554983
TI  - Characterisation of the xenogeneic immune response to microencapsulated fetal pig
      islet-like cell clusters transplanted into immunocompetent C57BL/6 mice.
AB  - Xenotransplantation of microencapsulated fetal pig islet-like cell clusters (FP
      ICCs) offers a potential cellular therapy for type 1 diabetes. Although
      microcapsules prevent direct contact of the host immune system with the
      xenografted tissue, poor graft survival is still an issue. This study aimed to
      characterise the nature of the host immune cells present on the engrafted
      microcapsules and effects on encapsulated FP ICCs that were transplanted into
      immunocompetent mice. Encapsulated FP ICCs were transplanted into the peritoneal
      cavity of C57BL/6 mice. Grafts retrieved at days 1, 3, 7, 14 and 21 post
      transplantation were analysed for pericapsular fibrotic overgrowth (PFO), cell
      viability, intragraft porcine gene expression, macrophages, myofibroblasts and
      intraperitoneal murine cytokines. Graft function was assessed ex vivo by insulin
      secretion studies. Xenogeneic immune response to encapsulated FP ICCs was
      associated with enhanced intragraft mRNA expression of porcine antigens MIP
      1alpha, IL-8, HMGB1 and HSP90 seen within the first two weeks post
      transplantation. This was associated with the recruitment of host macrophages,
      infiltration of myofibroblasts and collagen deposition leading to PFO which was
      evident from day 7 post-transplantation. This was accompanied by a decrease in
      cell viability and loss of FP ICC architecture. The only pro-inflammatory
      cytokine detected in the murine peritoneal flushing was TNF-alpha with levels
      peaking at day 7 post transplantation. This correlated with the onset of PFO at
      day 7 implying activated macrophages as its source. The anti-inflammatory
      cytokines detected were IL-5 and IL-4 with levels peaking at days 1 and 7,
      respectively. Porcine C-peptide was undetectable at all time points post
      transplantation. PFO was absent and murine intraperitoneal cytokines were
      undetectable when empty microcapsules were transplanted. In conclusion, this
      study demonstrated that the macrophages are direct effectors of the xenogeneic
      immune response to encapsulated FP ICCs leading to PFO mediated by a combination
      of both pro- and anti-inflammatory cytokines.

PMID- 23554984
TI  - Immunization with recombinant prion protein leads to partial protection in a
      murine model of TSEs through a novel mechanism.
AB  - Transmissible spongiform encephalopathies are neurodegenerative diseases, which
      despite fervent research remain incurable. Immunization approaches have shown
      great potential at providing protection, however tolerance effects hamper active
      immunization protocols. In this study we evaluated the antigenic potential of
      various forms of recombinant murine prion protein and estimated their protective
      efficacy in a mouse model of prion diseases. One of the forms tested provided a
      significant elongation of survival interval. The elongation was mediated via an
      acute depletion of mature follicular dendritic cells, which are associated with
      propagation of the prion infectious agent in the periphery and in part to the
      development of humoral immunity against prion protein. This unprecedented result
      could offer new strategies for protection against transmissible encephalopathies
      as well as other diseases associated with follicular dendritic cells.

PMID- 23554985
TI  - Evaluation of toxicity and biodegradability of cholinium amino acids ionic
      liquids.
AB  - Cholinium amino acid ionic liquids ([Ch][AA] ILs), which are wholly composed of
      renewable biomaterials, have recently been demonstrated to have very promising
      properties for applications in organic synthesis and biomass pretreatment. In
      this work, the toxicity of these ILs toward enzymes and bacteria was assessed,
      and the effect of the anion on these properties is discussed. The inhibitory
      potentials of this type of ILs to acetylcholinesterase were weaker approximately
      an order of magnitude than the traditional IL 1-butyl-3-methylimidazolium
      tetrafluoroborate. Additionally, the [Ch][AA] ILs displayed low toxicity toward
      the bacteria tested. Furthermore, the biodegradability of the [Ch][AA] ILs was
      evaluated via the closed bottle and CO(2) headspace tests using wastewater
      microorganisms. All the ILs were classified as 'readily biodegradable' based on
      their high levels of mineralization (62-87%). The presence of extra carboxyl or
      amide groups on the amino acid side chain rendered the ILs significantly more
      susceptible to microbial breakdown. In addition, for most of the [Ch][AA] ILs,
      low toxicity correlated with good biodegradability. The low toxicity and high
      biodegradability of these novel [Ch][AA] make them promising candidates for use
      as environmentally friendly solvents in large-scale applications.

PMID- 23554986
TI  - Mechanisms of adhesion and subsequent actions of a haematopoietic stem cell line,
      HPC-7, in the injured murine intestinal microcirculation in vivo.
AB  - OBJECTIVES: Although haematopoietic stem cells (HSCs) migrate to injured gut,
      therapeutic success clinically remains poor. This has been partially attributed
      to limited local HSC recruitment following systemic injection. Identifying site
      specific adhesive mechanisms underpinning HSC-endothelial interactions may
      provide important information on how to enhance their recruitment and thus
      potentially improve therapeutic efficacy. This study determined (i) the integrins
      and inflammatory cyto/chemokines governing HSC adhesion to injured gut and muscle
      (ii) whether pre-treating HSCs with these cyto/chemokines enhanced their adhesion
      and (iii) whether the degree of HSC adhesion influenced their ability to modulate
      leukocyte recruitment. METHODS: Adhesion of HPC-7, a murine HSC line, to
      ischaemia-reperfused (IR) injured mouse gut or cremaster muscle was monitored
      intravitally. Critical adhesion molecules were identified by pre-treating HPC-7
      with blocking antibodies to CD18 and CD49d. To identify cyto/chemokines capable
      of recruiting HPC-7, adhesion was monitored following tissue exposure to TNF
      alpha, IL-1beta or CXCL12. The effects of pre-treating HPC-7 with these
      cyto/chemokines on surface integrin expression/clustering, adhesion to ICAM
      1/VCAM-1 and recruitment in vivo was also investigated. Endogenous leukocyte
      adhesion following HPC-7 injection was again determined intravitally. RESULTS: IR
      injury increased HPC-7 adhesion in vivo, with intestinal adhesion dependent upon
      CD18 and muscle adhesion predominantly relying on CD49d. Only CXCL12 pre
      treatment enhanced HPC-7 adhesion within injured gut, likely by increasing CD18
      binding to ICAM-1 and/or CD18 surface clustering on HPC-7. Leukocyte adhesion was
      reduced at 4 hours post-reperfusion, but only when local HPC-7 adhesion was
      enhanced using CXCL12. CONCLUSION: This data provides evidence that site-specific
      molecular mechanisms govern HPC-7 adhesion to injured tissue. Importantly, we
      show that HPC-7 adhesion is a modulatable event in IR injury and further
      demonstrate that adhesion instigated by injury alone is not sufficient for
      mediating anti-inflammatory effects. Enhancing local HSC presence may therefore
      be essential to realising their clinical potential.

PMID- 23554988
TI  - Differences in lateral line morphology between hatchery- and wild-origin
      steelhead.
AB  - Despite identification of multiple factors mediating salmon survival, significant
      disparities in survival-to-adulthood among hatchery- versus wild-origin juveniles
      persist. In the present report, we explore the hypothesis that hatchery-reared
      juveniles might exhibit morphological defects in vulnerable mechanosensory
      systems prior to release from the hatchery, potentiating reduced survival after
      release. Juvenile steelhead (Oncorhynchus mykiss) from two different hatcheries
      were compared to wild-origin juveniles on several morphological traits including
      lateral line structure, otolith composition (a proxy for auditory function), and
      brain weight. Wild juveniles were found to possess significantly more superficial
      lateral line neuromasts than hatchery-reared juveniles, although the number of
      hair cells within individual neuromasts was not significantly different across
      groups. Wild juveniles were also found to possess primarily normal, aragonite
      containing otoliths, while hatchery-reared juveniles possessed a high proportion
      of crystallized (vaterite) otoliths. Finally, wild juveniles were found to have
      significantly larger brains than hatchery-reared juveniles. These differences
      together predict reduced sensitivity to biologically important hydrodynamic and
      acoustic signals from natural biotic (predator, prey, conspecific) and abiotic
      (turbulent flow, current) sources among hatchery-reared steelhead, in turn
      predicting reduced survival fitness after release. Physiological and behavioral
      studies are required to establish the functional significance of these
      morphological differences.

PMID- 23554987
TI  - Prospective validation of a prognostic model for respiratory syncytial virus
      bronchiolitis in late preterm infants: a multicenter birth cohort study.
AB  - OBJECTIVES: This study aimed to update and validate a prediction rule for
      respiratory syncytial virus (RSV) hospitalization in preterm infants 33-35 weeks
      gestational age (WGA). STUDY DESIGN: The RISK study consisted of 2 multicenter
      prospective birth cohorts in 41 hospitals. Risk factors were assessed at birth
      among healthy preterm infants 33-35 WGA. All hospitalizations for respiratory
      tract infection were screened for proven RSV infection by immunofluorescence or
      polymerase chain reaction. Multivariate logistic regression analysis was used to
      update an existing prediction model in the derivation cohort (n = 1,227). In the
      validation cohort (n = 1,194), predicted versus actual RSV hospitalization rates
      were compared to determine validity of the model. RESULTS: RSV hospitalization
      risk in both cohorts was comparable (5.7% versus 4.9%). In the derivation cohort,
      a prediction rule to determine probability of RSV hospitalization was developed
      using 4 predictors: family atopy (OR 1.9; 95%CI, 1.1-3.2), birth period (OR 2.6;
      1.6-4.2), breastfeeding (OR 1.7; 1.0-2.7) and siblings or daycare attendance (OR
      4.7; 1.7-13.1). The model showed good discrimination (c-statistic 0.703; 0.64
      0.76, 0.702 after bootstrapping). External validation showed good discrimination
      and calibration (c-statistic 0.678; 0.61-0.74). CONCLUSIONS: Our prospectively
      validated prediction rule identifies infants at increased RSV hospitalization
      risk, who may benefit from targeted preventive interventions. This prediction
      rule can facilitate country-specific, cost-effective use of RSV prophylaxis in
      late preterm infants.

PMID- 23554989
TI  - African elephants adjust speed in response to surface-water constraint on
      foraging during the dry-season.
AB  - Most organisms need to acquire various resources to survive and reproduce.
      Individuals should adjust their behavior to make optimal use of the landscape and
      limit the costs of trade-offs emerging from the use of these resources. Here we
      study how African elephants Loxodonta africana travel to foraging places between
      regular visits to waterholes. Elephant herds were tracked using GPS collars
      during two consecutive dry seasons in Hwange National Park, Zimbabwe. We
      segmented each individual movement track at each visit to water to define
      foraging trips, and then used trip-level statistics to build an understanding of
      movement strategies. Travel speed within these individually-consistent movement
      bouts was also analyzed to understand if speed was better linked to distance to
      water or progression in the trip over time. We found that elephants went further
      from water when drinking less often, which could result from a trade-off between
      drinking and foraging in less depleted, far from water, places. Speed increased
      towards the beginning and the end of the trips, and was also greater than
      observed during the wet season, suggesting that elephants were trying to save
      time. Numerous short trips traveled at greater speed, particularly when commuting
      to a different waterhole, was tentatively explained by the inability to drink at
      specific waterholes due to intra-specific interference. Unexpectedly elephants
      did not always minimize travel time by drinking at the closest waterhole, but the
      extra distance traveled remained never more than a few kilometers. Our results
      show how individuals may adjust movement behavior to deal with resource trade
      offs at the landscape scale. We also highlight how behavioral context, here
      progression in the trip, may be more important than spatial context, here
      distance to water, in explaining animal movement patterns.

PMID- 23554990
TI  - First insights into the genetic diversity of the pinewood nematode in its native
      area using new polymorphic microsatellite loci.
AB  - The pinewood nematode, Bursaphelenchus xylophilus, native to North America, is
      the causative agent of pine wilt disease and among the most important invasive
      forest pests in the East-Asian countries, such as Japan and China. Since 1999, it
      has been found in Europe in the Iberian Peninsula, where it also causes
      significant damage. In a previous study, 94 pairs of microsatellite primers have
      been identified in silico in the pinewood nematode genome. In the present study,
      specific PCR amplifications and polymorphism tests to validate these loci were
      performed and 17 microsatellite loci that were suitable for routine analysis of
      B. xylophilus genetic diversity were selected. The polymorphism of these markers
      was evaluated on nematodes from four field origins and one laboratory collection
      strain, all originate from the native area. The number of alleles and the
      expected heterozygosity varied between 2 and 11 and between 0.039 and 0.777,
      respectively. First insights into the population genetic structure of B.
      xylophilus were obtained using clustering and multivariate methods on the
      genotypes obtained from the field samples. The results showed that the pinewood
      nematode genetic diversity is spatially structured at the scale of the pine tree
      and probably at larger scales. The role of dispersal by the insect vector versus
      human activities in shaping this structure is discussed.

PMID- 23554991
TI  - Phylogenetically distinct bacteria involve extensive dechlorination of aroclor
      1260 in sediment-free cultures.
AB  - Microbial reductive dechlorination of the persistent polychlorinated biphenyls
      (PCBs) is attracting much attention in cleanup of the contaminated environment.
      Nevertheless, most PCB dechlorinating cultures require presence of sediment or
      sediment substitutes to maintain their dechlorination activities which hinders
      subsequent bacterial enrichment and isolation processes. The information on
      enriching sediment-free PCB dechlorinating cultures is still limited. In this
      study, 18 microcosms established with soils and sediments were screened for their
      dechlorination activities on a PCB mixture - Aroclor 1260. After one year of
      incubation, 10 out of 18 microcosms showed significant PCB dechlorination with
      distinct dechlorination patterns (e.g., Process H, N and T classified based on
      profiles of PCB congeners loss and new congeners formation). Through serial
      transfers in defined medium, six sediment-free PCB dechlorinating cultures (i.e.,
      CW-4, CG-1, CG-3, CG-4, CG-5 and SG-1) were obtained without amending any
      sediment or sediment-substitutes. PCB dechlorination Process H was the most
      frequently observed dechlorination pattern, which was found in four sediment-free
      cultures (CW-4, CG-3, CG-4 and SG-1). Sediment-free culture CG-5 showed the most
      extensive PCB dechlorination among the six cultures, which was mediated by
      Process N, resulting in the accumulation of penta- (e.g., 236-24-CB) and tetra
      chlorobiphenyls (tetra-CBs) (e.g., 24-24-CB, 24-25-CB, 24-26-CB and 25-26-CB) via
      dechlorinating 30.44% hepta-CBs and 59.12% hexa-CBs after three months of
      incubation. For culture CG-1, dechlorinators mainly attacked double flanked meta
      chlorines and partially ortho-chlorines, which might represent a novel
      dechlorination pattern. Phylogenetic analysis showed distinct affiliation of PCB
      dechlorinators in the microcosms, including Dehalogenimonas and Dehalococcoides
      species. This study broadens our knowledge in microbial reductive dechlorination
      of PCBs, and provides essential information for culturing and stimulating PCB
      dechlorinators for in situ bioremediation applications.

PMID- 23554992
TI  - Careful selection of reference genes is required for reliable performance of RT
      qPCR in human normal and cancer cell lines.
AB  - Reverse Transcription - quantitative Polymerase Chain Reaction (RT-qPCR) is a
      standard technique in most laboratories. The selection of reference genes is
      essential for data normalization and the selection of suitable reference genes
      remains critical. Our aim was to 1) review the literature since implementation of
      the MIQE guidelines in order to identify the degree of acceptance; 2) compare
      various algorithms in their expression stability; 3) identify a set of suitable
      and most reliable reference genes for a variety of human cancer cell lines. A
      PubMed database review was performed and publications since 2009 were selected.
      Twelve putative reference genes were profiled in normal and various cancer cell
      lines (n = 25) using 2-step RT-qPCR. Investigated reference genes were ranked
      according to their expression stability by five algorithms (geNorm, Normfinder,
      BestKeeper, comparative DeltaCt, and RefFinder). Our review revealed 37
      publications, with two thirds patient samples and one third cell lines. qPCR
      efficiency was given in 68.4% of all publications, but only 28.9% of all studies
      provided RNA/cDNA amount and standard curves. GeNorm and Normfinder algorithms
      were used in 60.5% in combination. In our selection of 25 cancer cell lines, we
      identified HSPCB, RRN18S, and RPS13 as the most stable expressed reference genes.
      In the subset of ovarian cancer cell lines, the reference genes were PPIA, RPS13
      and SDHA, clearly demonstrating the necessity to select genes depending on the
      research focus. Moreover, a cohort of at least three suitable reference genes
      needs to be established in advance to the experiments, according to the
      guidelines. For establishing a set of reference genes for gene normalization we
      recommend the use of ideally three reference genes selected by at least three
      stability algorithms. The unfortunate lack of compliance to the MIQE guidelines
      reflects that these need to be further established in the research community.

PMID- 23554993
TI  - Alteration of the thymic T cell repertoire by rotavirus infection is associated
      with delayed type 1 diabetes development in non-obese diabetic mice.
AB  - Rotaviruses are implicated as a viral trigger for the acceleration of type 1
      diabetes in children. Infection of adult non-obese diabetic (NOD) mice with
      rotavirus strain RRV accelerates diabetes development, whereas RRV infection in
      infant NOD mice delays diabetes onset. In this study of infant mice, RRV titers
      and lymphocyte populations in the intestine, mesenteric lymph nodes (MLN) and
      thymus of NOD mice were compared with those in diabetes-resistant BALB/c and
      C57BL/6 mice. Enhanced intestinal RRV infection occurred in NOD mice compared
      with the other mouse strains. This was associated with increases in the frequency
      of CD8alphabeta TCRalphabeta intraepithelial lymphocytes, and their PD-L1
      expression. Virus spread to the MLN and T cell numbers there also were greatest
      in NOD mice. Thymic RRV infection is shown here in all mouse strains, often in
      combination with alterations in T cell ontogeny. Infection lowered thymocyte
      numbers in infant NOD and C57BL/6 mice, whereas thymocyte production was
      unaltered overall in infant BALB/c mice. In the NOD mouse thymus, effector CD4(+)
      T cell numbers were reduced by infection, whereas regulatory T cell numbers were
      maintained. It is proposed that maintenance of thymic regulatory T cell numbers
      may contribute to the increased suppression of inflammatory T cells in response
      to a strong stimulus observed in pancreatic lymph nodes of adult mice infected as
      infants. These findings show that rotavirus replication is enhanced in diabetes
      prone mice, and provide evidence that thymic T cell alterations may contribute to
      the delayed diabetes onset following RRV infection.

PMID- 23554994
TI  - Application of palladium-mediated (18)F-fluorination to PET radiotracer
      development: overcoming hurdles to translation.
AB  - New chemistry methods for the synthesis of radiolabeled small molecules have the
      potential to impact clinical positron emission tomography (PET) imaging, if they
      can be successfully translated. However, progression of modern reactions from the
      stage of synthetic chemistry development to the preparation of radiotracer doses
      ready for use in human PET imaging is challenging and rare. Here we describe the
      process of and the successful translation of a modern palladium-mediated
      fluorination reaction to non-human primate (NHP) baboon PET imaging-an important
      milestone on the path to human PET imaging. The method, which transforms
      [(18)F]fluoride into an electrophilic fluorination reagent, provides access to
      aryl-(18)F bonds that would be challenging to synthesize via conventional
      radiochemistry methods.

PMID- 23554995
TI  - A rat model for muscle regeneration in the soft palate.
AB  - BACKGROUND: Children with a cleft in the soft palate have difficulties with
      speech, swallowing, and sucking. Despite successful surgical repositioning of the
      muscles, optimal function is often not achieved. Scar formation and defective
      regeneration may hamper the functional recovery of the muscles after cleft palate
      repair. Therefore, the aim of this study is to investigate the anatomy and
      histology of the soft palate in rats, and to establish an in vivo model for
      muscle regeneration after surgical injury. METHODS: Fourteen adult male Sprague
      Dawley rats were divided into four groups. Groups 1 (n = 4) and 2 (n = 2) were
      used to investigate the anatomy and histology of the soft palate, respectively.
      Group 3 (n = 6) was used for surgical wounding of the soft palate, and group 4 (n
      = 2) was used as unwounded control group. The wounds (1 mm) were evaluated by
      (immuno)histochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA) after 7
      days. RESULTS: The present study shows that the anatomy and histology of the soft
      palate muscles of the rat is largely comparable with that in humans. All wounds
      showed clinical evidence of healing after 7 days. AZAN staining demonstrated
      extensive collagen deposition in the wound area, and initial regeneration of
      muscle fibers and salivary glands. Proliferating and differentiating satellite
      cells were identified in the wound area by antibody staining. CONCLUSIONS: This
      model is the first, suitable for studying muscle regeneration in the rat soft
      palate, and allows the development of novel adjuvant strategies to promote muscle
      regeneration after cleft palate surgery.

PMID- 23554997
TI  - Magnetic compass orientation in the European eel.
AB  - European eel migrate from freshwater or coastal habitats throughout Europe to
      their spawning grounds in the Sargasso Sea. However, their route (~ 6000 km) and
      orientation mechanisms are unknown. Several attempts have been made to prove the
      existence of magnetoreception in Anguilla sp., but none of these studies have
      demonstrated magnetic compass orientation in earth-strength magnetic field
      intensities. We tested eels in four altered magnetic field conditions where
      magnetic North was set at geographic North, South, East, or West. Eels oriented
      in a manner that was related to the tank in which they were housed before the
      test. At lower temperature (under 12 degrees C), their orientation relative to
      magnetic North corresponded to the direction of their displacement from the
      holding tank. At higher temperatures (12-17 degrees C), eels showed bimodal
      orientation along an axis perpendicular to the axis of their displacement. These
      temperature-related shifts in orientation may be linked to the changes in
      behavior that occur between the warm season (during which eels are foraging) and
      the colder fall and winter (during which eels undertake their migrations). These
      observations support the conclusion that 1. eels have a magnetic compass, and 2.
      they use this sense to orient in a direction that they have registered moments
      before they are displaced. The adaptive advantage of having a magnetic compass
      and learning the direction in which they have been displaced becomes clear when
      set in the context of the eel's seaward migration. For example, if their
      migration is halted or blocked, as it is the case when environmental conditions
      become unfavorable or when they encounter a barrier, eels would be able to resume
      their movements along their old bearing when conditions become favorable again or
      when they pass by the barrier.

PMID- 23554996
TI  - Subclinical thyroid dysfunction and cognitive decline in old age.
AB  - BACKGROUND: Subclinical thyroid dysfunction has been implicated as a risk factor
      for cognitive decline in old age, but results are inconsistent. We investigated
      the association between subclinical thyroid dysfunction and cognitive decline in
      the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS:
      Prospective longitudinal study of men and women aged 70-82 years with pre
      existing vascular disease or more than one risk factor to develop this condition
      (N = 5,154). Participants taking antithyroid medications, thyroid hormone
      supplementation and/or amiodarone were excluded. Thyroid function was measured at
      baseline: subclinical hyper- and hypothyroidism were defined as thyroid
      stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal
      levels of free thyroxine (FT4). Cognitive performance was tested at baseline and
      at four subsequent time points during a mean follow-up of 3 years, using five
      neuropsychological performance tests. RESULTS: Subclinical hyperthyroidism and
      hypothyroidism were found in 65 and 161 participants, respectively. We found no
      consistent association of subclinical hyper- or hypothyroidism with altered
      cognitive performance compared to euthyroid participants on the individual
      cognitive tests. Similarly, there was no association with rate of cognitive
      decline during follow-up. CONCLUSION: We found no consistent evidence that
      subclinical hyper- or hypothyroidism contribute to cognitive impairment or
      decline in old age. Although our data are not in support of treatment of
      subclinical thyroid dysfunction to prevent cognitive dysfunction in later life,
      only large randomized controlled trials can provide definitive evidence.

PMID- 23554998
TI  - Low prevalence of Cfr-mediated linezolid resistance among methicillin-resistant
      Staphylococcus aureus in a Spanish hospital: case report on linezolid resistance
      acquired during linezolid therapy.
AB  - Linezolid is an effective antimicrobial agent to treat methicillin-resistant
      Staphylococcus aureus (MRSA). Resistance to linezolid due to the cfr gene is
      described worldwide. The present study aimed to analyze the prevalence of the cfr
      mediated linezolid resistance among MRSA clinical isolates in our area. A very
      low prevalence of cfr mediated linezolid resistance was found: only one
      bacteremic isolate out of 2 215 screened isolates. The only linezolid resistant
      isolate arose in a patient, previously colonized by MRSA, following linezolid
      therapy. Despite the low rate of resistance in our area, ongoing surveillance is
      advisable to avoid the spread of linezolid resistance.

PMID- 23554999
TI  - Expression and secretion of human proinsulin-B10 from mouse salivary glands:
      implications for the treatment of type I diabetes mellitus.
AB  - Adenovirus (Ad) mediated expression of therapeutic proteins from salivary glands
      can result in the delivery of biologically active proteins into the circulation
      where they impart their physiological function. In recent years, Ad vector
      delivery to salivary glands (SGs) has emerged as a viable option for gene
      therapy. Here, we engineered a variant of human proinsulin (hProinsulin-B10) into
      an Ad vector and demonstrated its ability to transduce cell lines, and express a
      bioactive protein that induces the phosphorylation of AKT, a key insulin
      signaling molecule. We also examined its expression in mice following delivery of
      the vector to the parotid gland (PTG), the submandibular gland (SMG) or to the
      liver via the tail vein and assessed transgenic protein expression and vector
      containment for each delivery method. In all cases, hProinsulin-B10 was expressed
      and secreted into the circulation. Lower levels of circulating hProinsulin-B10
      were obtained from the PTG while higher levels were obtained from the tail vein
      and the SMG; however, vector particle containment was best when delivered to the
      SMG. Expression of hProinsulin-B10 in the SMG of chemically induced diabetic mice
      prevented excessive hyperglycemia observed in untreated mice. These results
      demonstrate that hProinsulin-B10 can be expressed and secreted into the
      circulation from SGs and can function physiologically in vivo. The ability to
      remediate a diabetic phenotype in a model of type 1 diabetes mellitus is the
      first step in an effort that may lead to a possible therapy for diabetes.

PMID- 23555000
TI  - Prevalence of symptomatic heart failure with reduced and with normal ejection
      fraction in an elderly general population-the CARLA study.
AB  - BACKGROUND/OBJECTIVES: Chronic heart failure (CHF) is one of the most important
      public health concerns in the industrialized world having increasing incidence
      and prevalence. Although there are several studies describing the prevalence of
      heart failure with reduced ejection fraction (HFREF) and heart failure with
      normal ejection fraction (HFNEF) in selected populations, there are few data
      regarding the prevalence and the determinants of symptomatic heart failure in the
      general population. METHODS: Cross-sectional data of a population-based German
      sample (1,779 subjects aged 45-83 years) were analyzed to determine the
      prevalence and determinants of chronic SHF and HFNEF defined according to the
      European Society of Cardiology using symptoms, echocardiography and serum NT
      proBNP. Prevalence was age-standardized to the German population as of December
      31st, 2005. RESULTS: The overall age-standardized prevalence of symptomatic CHF
      was 7.7% (95%CI 6.0-9.8) for men and 9.0% (95%CI 7.0-11.5) for women. The
      prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old
      subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be
      shown in 48% (n = 78), symptomatic HFNEF in 52% (n = 85) of subjects with CHF.
      The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8) for women and
      4.6 % (95%CI 3.6-6.3) for men. The age-standardized prevalence of HFNEF for women
      and men was 5.1 % (95%CI 3.8-7.0) and 3.0 % (95%CI 2.1-4.5), respectively.
      Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3)
      or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5).
      CONCLUSION: The prevalence of symptomatic CHF appears high in this population
      compared with other studies. While more women were affected by HFNEF than men,
      more male subjects suffered from HFREF. The high prevalence of symptomatic CHF
      seems likely to be mainly due to the high prevalence of cardiovascular risk
      factors in this population.

PMID- 23555001
TI  - Left atrial appendages from adult hearts contain a reservoir of diverse cardiac
      progenitor cells.
AB  - AIMS: There is strong evidence supporting the claim that endogenous cardiac
      progenitor cells (CPCs) are key players in cardiac regeneration, but the anatomic
      source and phenotype of the master cardiac progenitors remains uncertain. Our aim
      was to investigate the different cardiac stem cell populations in the left atrial
      appendage (LAA) and their fates. METHODS AND RESULTS: We investigated the CPC
      content and profile of adult murine LAAs using immunohistochemistry and flow
      cytometry. We demonstrate that the LAA contains a large number of CPCs relative
      to other areas of the heart, representing over 20% of the total cell number. We
      grew two distinct CPC populations from the LAA by varying the degree of
      proteolysis. These differed by their histological location, surface marker
      profiles and growth dynamics. Specifically, CD45(pos) cells grew with milder
      proteolysis, while CD45(neg) cells grew mainly with more intense proteolysis.
      Both cell types could be induced to differentiate into cells with cardiomyocyte
      markers and organelles, albeit by different protocols. Many CD45(pos) cells
      expressed CD45 initially and rapidly lost its expression while differentiating.
      CONCLUSIONS: Our results demonstrate that the left atrial appendage plays a role
      as a reservoir of multiple types of progenitor cells in murine adult hearts. Two
      different types of CPCs were isolated, differing in their epicardial-myocardial
      localization. Considering studies demonstrating layer-specific origins of
      different cardiac progenitor cells, our findings may shed light on possible
      pathways to study and utilize the diversity of endogenous progenitor cells in the
      adult heart.

PMID- 23555002
TI  - Stably luminescent Staphylococcus aureus clinical strains for use in
      bioluminescent imaging.
AB  - In vivo bioluminescent imaging permits the visualization of bacteria in live
      animals, allowing researchers to monitor, both temporally and spatially, the
      progression of infection in each animal. We sought to engineer stably luminescent
      clinical strains of Staphylococcus aureus, with the goal of using such strains in
      mouse models. The gram-positive shuttle vector pMAD was used as the backbone for
      an integration plasmid. A chloramphenicol resistance gene, a modified lux operon
      from Photorhabdus luminescens, and approximately 650 bp of homology to the
      chromosome of the USA300 S. aureus strain NRS384 were added, generating plasmid
      pRP1195. Electroporation into strain RN4220 followed by temperature shift led to
      integration of pRP1195 into the chromosome. The integrated plasmid was
      transferred to clinical strains by phage transduction. Luminescent strains
      displayed no in vitro growth defects. Moreover, luminescence was stable in vitro
      after three rounds of subculture over 48 hours of growth in the absence of
      antibiotics. Mice were infected with a luminescent strain of NRS384 in skin and
      intravenous models. In a mouse skin model, luminescent bacteria were present in
      lesions that formed and cleared over the course of several days, and in an
      intravenous model, bacteria inoculated in the mouse tail vein were observed
      spreading to multiple tissues. No statistically significant difference in
      virulence was observed between NRS384 and the luminescent strain in either
      infection model. These preliminary data suggest that this luminescent USA300
      strain is suitable for use in mouse models. Similar strains were engineered using
      other sequenced clinical strains. Because these strains are stably luminescent,
      they should prove useful in animal models of infection.

PMID- 23555003
TI  - Association rule mining and network analysis in oriental medicine.
AB  - Extracting useful and meaningful patterns from large volumes of text data is of
      growing importance. In the present study we analyze vast amounts of prescription
      data, generated from the book of oriental medicine to identify the relationships
      between the symptoms and the associated medicines used to treat these symptoms.
      The oriental medicine book used in this study (called Bangyakhappyeon) contains a
      large number of prescriptions to treat about 54 categorized symptoms and lists
      the corresponding herbal materials. We used an association rule algorithm
      combined with network analysis and found useful and informative relationships
      between the symptoms and medicines.

PMID- 23555004
TI  - SWAP-70: a new type of oncogene.
AB  - SWAP-70 is a protein that has been suggested to be involved in regulation of
      actin rearrangement. Having discovered that an artificially-derived mutant of
      SWAP-70 can transform mouse embryo fibroblasts, we searched for naturally
      occurring mutations in the SWAP-70 gene, finding listings for several on the Web
      at www.sanger.ac.uk/genetics/CGP/cosmic/, including three mutations found in
      ovarian cancers. (The number of such mutations has now reached 13 out of 228
      tumors). We created expression vectors for the mutant SWAP-70 proteins and
      introduced these into NIH3T3 cells. The cells expressing the mutant SWAP-70
      constructs exhibited faster growth than the parental or wild-type SWAP-70
      expressing cells. In most instances, cells that are able to grow in soft agar
      will form tumors in nude mice. While SWAP-70-transformed cells grew in soft agar,
      they failed to form tumors in nude mice. This result implies that transformation
      by the SWAP-70 mutants is unique. The cells bearing the mutant SWAP-70 genes were
      sensitive to nutrient starvation, supporting the idea that they are transformed
      cells. However, they failed to pile up and demonstrated contact inhibition,
      unlike most normal transformed cells. Upon expression of human SWAP-70 genes,
      MEK1 was activated. This activation appeared to contribute to the saturation
      density of the cells. As SWAP-70 has been shown to be the last protein to receive
      signals from cytokines, it is likely that there is a putative feedback signaling
      pathway, and that disorder of this signaling pathway can transform cells.
      Accordingly, this may explain why SWAP-70-transformed cells have different
      characteristics than most transformed cells.

PMID- 23555005
TI  - Vax1/2 genes counteract Mitf-induced respecification of the retinal pigment
      epithelium.
AB  - During vertebrate eye development, the transcription factor MITF acts to promote
      the development of the retinal pigment epithelium (RPE). In embryos with Mitf
      mutations, the future RPE hyperproliferates and is respecified as retinal tissue
      but only in a small portion of the dorsal RPE. Using a series of genetic crosses,
      we show that this spatial restriction of RPE respecification is brought about by
      persistent expression of the anti-retinogenic ventral homeodomain gene Vax2 in
      the dorso-proximal and both Vax1 and Vax2 in the ventral RPE. We further show
      that dorso-proximal RPE respecification in Vax2/Mitf double mutants and dorso
      proximal and ventral RPE respecification in Vax1/2/Mitf triple mutants result
      from increased FGF/MAP kinase signaling. In none of the mutants, however, does
      the distal RPE show signs of hyperproliferation or respecification, likely due to
      local JAGGED1/NOTCH signaling. Expression studies and optic vesicle culture
      experiments also suggest a role for NOTCH signaling within the mutant dorsal RPE
      domains, where ectopic JAGGED1 expression may partially counteract the effects of
      FGF/ERK1/2 signaling on RPE respecification. The results indicate the presence of
      complex interplays between distinct transcription factors and signaling molecules
      during eye development and show how RPE phenotypes associated with mutations in
      one gene are modulated by expression changes in other genes.

PMID- 23555006
TI  - Genetic variant rs7758229 in 6q26-q27 is not associated with colorectal cancer
      risk in a Chinese population.
AB  - BACKGROUND: A recent genome-wide association study has identified a new genetic
      variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese
      population, but it is unknown whether this newly identified variant is associated
      with colorectal cancer in other populations, including the Chinese population.
      METHODS: We examined the associations between rs7758229 and colorectal cancer
      risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic
      regression model was used to assess the associations. RESULTS: No significant
      association was found between rs7758229 and colorectal cancer risk (OR = 0.95,
      95%CI = 0.84-1.09, P = 0.463). Similar results were observed in the
      stratification of tumor location (OR = 0.94, 95%CI = 0.80-1.11, P = 0.481 for
      colon cancer, and OR = 0.96, 95%CI = 0.82-1.13, P = 0.621 for rectum cancer).
      CONCLUSIONS: Our findings did not support an association between rs7758229 in
      6q26-q27 and the risk of colorectal cancer in a Chinese population.

PMID- 23555007
TI  - Sinomenine protects against lipopolysaccharide-induced acute lung injury in mice
      via adenosine A(2A) receptor signaling.
AB  - Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal
      plant Sinomenium acutum, which is widely used in the clinical treatment of
      rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is
      unclear. In this study, we investigate the role of SIN in lipopolysaccharide
      (LPS)-induced ALI in mice. After ALI, lung water content and histological signs
      of pulmonary injury were attenuated, whereas the PaO2/FIO2 (P/F) ratios were
      elevated significantly in the mice pretreated with SIN. Additionally, SIN
      markedly inhibited inflammatory cytokine TNF-alpha and IL-1beta expression levels
      as well as neutrophil infiltration in the lung tissues of the mice. Microarray
      analysis and real-time PCR showed that SIN treatment upregulated adenosine A(2A)
      receptor (A(2A)R) expression, and the protective effect of SIN was abolished in
      A(2A)R knockout mice. Further investigation in isolated mouse neutrophils
      confirmed the upregulation of A(2A)R by SIN and showed that A(2A)R-cAMP-PKA
      signaling was involved in the anti-inflammatory effect of SIN. Taken together,
      these findings demonstrate an A(2A)R-associated anti-inflammatory effect and the
      protective role of SIN in ALI, which suggests a potential novel approach to treat
      ALI.

PMID- 23555009
TI  - Using RNA-Seq to profile soybean seed development from fertilization to maturity.
AB  - To understand gene expression networks leading to functional properties and
      compositional traits of the soybean seed, we have undertaken a detailed
      examination of soybean seed development from a few days post-fertilization to the
      mature seed using Illumina high-throughput transcriptome sequencing (RNA-Seq).
      RNA was sequenced from seven different stages of seed development, yielding
      between 12 million and 78 million sequenced transcripts. These have been aligned
      to the 79,000 gene models predicted from the soybean genome recently sequenced by
      the Department of Energy Joint Genome Institute. Over one hundred gene models
      were identified with high expression exclusively in young seed stages, starting
      at just four days after fertilization. These were annotated as being related to
      many basic components and processes such as histones and proline-rich proteins.
      Genes encoding storage proteins such as glycinin and beta-conglycinin had their
      highest expression levels at the stages of largest fresh weight, confirming
      previous knowledge that these storage products are being rapidly accumulated
      before the seed begins the desiccation process. Other gene models showed high
      expression in the dry, mature seeds, perhaps indicating the preparation of
      pathways needed later, in the early stages of imbibition. Many highly-expressed
      gene models at the dry seed stage are, as expected, annotated as hydrophilic
      proteins associated with low water conditions, such as late embryogenesis
      abundant (LEA) proteins and dehydrins, which help preserve the cellular
      structures and nutrients within the seed during desiccation. More significantly,
      the power of RNA-Seq to detect genes expressed at low levels revealed hundreds of
      transcription factors with notable expression in at least one stage of seed
      development. Results from a second biological replicate demonstrate high
      reproducibility of these data revealing a comprehensive view of the transciptome
      of seed development in the cultivar Williams, the reference cultivar for the
      first soybean genome sequence.

PMID- 23555008
TI  - Structural properties of PAS domains from the KCNH potassium channels.
AB  - KCNH channels form an important family of voltage gated potassium channels. These
      channels include a N-terminal Per-Arnt-Sim (PAS) domain with unknown function. In
      other proteins PAS domains are implicated in cellular responses to environmental
      queues through small molecule binding or involvement in signaling cascades. To
      better understand their role we characterized the structural properties of
      several channel PAS domains. We determined high resolution structures of PAS
      domains from the mouse EAG (mEAG), drosophila ELK (dELK) and human ERG (hERG)
      channels and also of the hERG domain without the first nine amino acids. We
      analyzed these structures for features connected to ligand binding and signaling
      in other PAS domains. In particular, we have found cavities in the hERG and mEAG
      structures that share similarities with the ligand binding sites from other PAS
      domains. These cavities are lined by polar and apolar chemical groups and display
      potential flexibility in their volume. We have also found that the hydrophobic
      patch on the domain beta-sheet is a conserved feature and appears to drive the
      formation of protein-protein contacts. In addition, the structures of the dELK
      domain and of the truncated hERG domain revealed the presence of N-terminal
      helices. These helices are equivalent to the helix described in the hERG NMR
      structures and are known to be important for channel function. Overall, these
      channel domains retain many of the PAS domain characteristics known to be
      important for cell signaling.

PMID- 23555010
TI  - Influenza vaccination uptake among the working age population of Japan: results
      from a national cross-sectional survey.
AB  - BACKGROUND: Influenza vaccination rates among Japanese people of working age (20
      69 years) is currently suboptimal, and the reasons for this have not been clearly
      elucidated. This study examined factors associated with vaccination intention
      among the working age population in Japan during September 2011, one-month prior
      to influenza vaccination becoming available. METHODOLOGY/PRINCIPAL FINDINGS: A
      web-based survey of intention to be vaccinated against influenza in the coming
      season was undertaken among 3,129 Japanese aged 20 to 69 years. Multinomial
      logistic regression analysis was used to explore the associations between
      vaccination intent and other variables. Influenza vaccination intent was
      associated with having been vaccinated in the previous year (Odds Ratio (OR):
      3.81; 95% Confidence Interval (CI): 3.75-3.86), the number of children per
      household (one compared with zero; OR: 1.37; 95%CI: 1.11-1.65), and household
      income ($50,000 to <$100,000 compared with $0 to <$50,000; OR: 1.30; 95%CI: 1.07
      1.54). Smoking was inversely associated with influenza vaccine uptake (current
      smokers compared with non-smokers; OR: 0.79; 95%CI: 0.61-0.98). A history of
      either the survey respondent or a household member having being medically
      diagnosed with influenza in the previous year was not statistically associated
      with future influenza vaccination intent. CONCLUSIONS/SIGNIFICANCE: Overall, this
      suggests that intention to be vaccinated among working age Japanese is associated
      with a past history of influenza vaccination, having children, and the
      household's income. As such, consideration of these factors should now form the
      cornerstone of strategies to encourage increased uptake of vaccination against
      influenza in future years.

PMID- 23555011
TI  - Combined TLR2/4-activated dendritic/tumor cell fusions induce augmented cytotoxic
      T lymphocytes.
AB  - Induction of antitumor immunity by dendritic cell (DC)-tumor fusion cells
      (DC/tumor) can be modulated by their activation status. In this study, to address
      optimal status of DC/tumor to induce efficient antigen-specific cytotoxic T
      lymphocytes (CTLs), we have created various types of DC/tumor: 1) un-activated
      DC/tumor; 2) penicillin-killed Streptococcus pyogenes (OK-432; TLR4 agonist)
      activated DC/tumor; 3) protein-bound polysaccharides isolated from Coriolus
      versicolor (PSK; TLR2 agonist)-activated DC/tumor; and 4) Combined OK-432- and
      PSK-activated DC/tumor. Moreover, we assessed the effects of TGF-beta1 derived
      from DC/tumor on the induction of MUC1-specific CTLs. Combined TLR2- and TLR4
      activated DC/tumor overcame immune-suppressive effect of TGF-beta1 in comparison
      to those single activated or un-activated DC/tumor as demonstrated by: 1) up
      regulation of MHC class II and CD86 expression on DC/tumor; 2) increased fusion
      efficiency; 3) increased production of fusions derived IL-12p70; 4) activation of
      CD4(+) and CD8(+) T cells that produce high levels of IFN-gamma; 5) augmented
      induction of CTL activity specific for MUC1; and 6) superior efficacy in
      inhibiting CD4(+)CD25(+)Foxp3(+) T cell generation. However, DC/tumor-derived TGF
      beta1 reduced the efficacy of DC/tumor vaccine in vitro. Incorporating combined
      TLRs-activation and TGF-beta1-blockade of DC/tumor may enhance the effectiveness
      of DC/tumor-based cancer vaccines and have the potential applicability to the
      field of adoptive immunotherapy.

PMID- 23555012
TI  - Temporal and pharmacological characterization of angiostatin release and
      generation by human platelets: implications for endothelial cell migration.
AB  - Platelets play an important role in thrombosis and in neo-vascularisation as they
      release and produce factors that both promote and suppress angiogenesis. Amongst
      these factors is the angiogenesis inhibitor angiostatin, which is released during
      thrombus formation. The impact of anti-thrombotic agents and the kinetics of
      platelet angiostatin release are unknown. Hence, our objectives were to
      characterize platelet angiostatin release temporally and pharmacologically and to
      determine how angiostatin release influences endothelial cell migration, an early
      stage of angiogenesis. We hypothesized anti-platelet agents would suppress
      angiostatin release but not generation by platelets. Human platelets were
      aggregated and temporal angiostatin release was compared to vascular endothelial
      growth factor (VEGF). Immuno-gold electron microscopy and immunofluorescence
      microscopy identified alpha-granules as storage organelles of platelet
      angiostatin. Acetylsalicylic acid, MRS2395, GPIIb/IIIa blocking peptide, and
      aprotinin were used to characterize platelet angiostatin release and generation.
      An endothelial cell migration assay was performed under hypoxic conditions to
      determine the effects of pharmacological platelet and angiostatin inhibition.
      Compared to VEGF, angiostatin generation and release from alpha-granules occurred
      later temporally during platelet aggregation. Consequently, collagen-activated
      platelet releasates stimulated endothelial cell migration more potently than
      maximally-aggregated platelets. Platelet inhibitors prostacyclin, S-nitroso
      glutathione, acetylsalicylic acid, and GPIIb/IIIa blocking peptide, but not a
      P2Y12 inhibitor, suppressed angiostatin release but not generation. Suppression
      of angiostatin generation in the presence of acetylsalicylic acid enhanced
      platelet-stimulated endothelial migration. Hence, the temporal and
      pharmacological modulation of platelet angiostatin release may have significant
      consequences for neo-vascularization following thrombus formation.

PMID- 23555013
TI  - Modelling adaptation to directional motion using the Adelson-Bergen energy
      sensor.
AB  - The motion energy sensor has been shown to account for a wide range of
      physiological and psychophysical results in motion detection and discrimination
      studies. It has become established as the standard computational model for
      retinal movement sensing in the human visual system. Adaptation effects have been
      extensively studied in the psychophysical literature on motion perception, and
      play a crucial role in theoretical debates, but the current implementation of the
      energy sensor does not provide directly for modelling adaptation-induced changes
      in output. We describe an extension of the model to incorporate changes in output
      due to adaptation. The extended model first computes a space-time representation
      of the output to a given stimulus, and then a RC gain-control circuit ("leaky
      integrator") is applied to the time-dependent output. The output of the extended
      model shows effects which mirror those observed in psychophysical studies of
      motion adaptation: a decline in sensor output during stimulation, and changes in
      the relative of outputs of different sensors following this adaptation.

PMID- 23555014
TI  - Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV
      coinfection.
AB  - OBJECTIVES: To investigate whether T-cell activation and exhaustion is linked to
      HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T
      cell characteristics in HIV/HCV coinfected patients and controls. METHODS: 14
      HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15
      healthy controls were included in this cross-sectional study. Differences in
      expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and
      Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow
      cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver
      fibrosis). RESULTS: Frequencies of activated CD4(+) and CD8(+) T-cells were
      higher in HIV/HCV-coinfected compared to healthy controls and HCV or HIV mono
      infected individuals. Coinfected patients also showed high expression of the
      exhaustion marker PD-1 and death receptor Fas. In contrast, the exhaustion marker
      Tim-3 was only elevated in HIV-monoinfected patients. T-cell activation and
      exhaustion were correlated with HCV-RNA, suggesting that viral antigen influences
      T-cell activation and exhaustion. Interestingly, increased percentages of
      effector CD8(+) T-cells were found in patients with severe (F3-F4) liver fibrosis
      compared to those with no to minimal fibrosis (F0-F2). CONCLUSIONS: HIV/HCV
      coinfected patients display a high level of T-cell activation and exhaustion in
      the peripheral blood. Our data suggest that T-cell activation and exhaustion are
      influenced by the level of HCV viremia. Furthermore, high percentages of
      cytotoxic/effector CD8(+) T-cells are associated with liver fibrosis in both HCV
      monoinfected and HIV/HCV coinfected patients.

PMID- 23555015
TI  - Rab GTPases regulate endothelial cell protein C receptor-mediated endocytosis and
      trafficking of factor VIIa.
AB  - Recent studies have established that factor VIIa (FVIIa) binds to the endothelial
      cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis
      of this receptor/ligand complex. Rab GTPases are known to play a crucial role in
      the endocytic and exocytic pathways of receptors or receptor/ligand complexes.
      The present study was undertaken to investigate the role of Rab GTPases in the
      intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical
      vein endothelial cells (HUVEC) were transduced with recombinant adenoviral
      vectors to express wild-type, constitutively active, or dominant negative mutant
      of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488
      fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR,
      and Rab proteins was evaluated by immunofluorescence confocal microscopy. In
      cells expressing wild-type or constitutively active Rab4A, internalized AF488
      FVIIa accumulated in early/sorting endosomes and its entry into the recycling
      endosomal compartment (REC) was inhibited. Expression of constitutively active
      Rab5A induced large endosomal structures beneath the plasma membrane where EPCR
      and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR
      FVIIa. Expression of constitutively active Rab11 resulted in retention of
      accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative
      form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and
      prevented entry of internalized FVIIa into the REC. Expression of dominant
      negative Rab11 also inhibited the transport of FVIIa across the endothelium.
      Overall our data show that Rab GTPases regulate the internalization and
      intracellular trafficking of EPCR-FVIIa.

PMID- 23555016
TI  - Magnetic resonance imaging at 7T reveals common events in age-related sarcopenia
      and in the homeostatic response to muscle sterile injury.
AB  - Skeletal muscle remodeling in response to various noxae physiologically includes
      structural changes and inflammatory events. The possibility to study those
      phenomena in-vivo has been hampered by the lack of validated imaging tools. In
      our study, we have relied on multiparametric magnetic resonance imaging for
      quantitative monitoring of muscle changes in mice experiencing age-related
      sarcopenia or active regeneration after sterile acute injury of tibialis anterior
      muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils'
      necrosis, leukocyte infiltration, and regeneration have been evaluated and
      compared with parameters from magnetic resonance imaging: T2-mapping (T2
      relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.)
      and diffusion weighted imaging (apparent diffusion coefficient, ADC).
      Inflammatory leukocytes within the perimysium and heterogeneous size of fibers
      characterized aged muscles. They displayed significantly increased T2-rt (P<0.05)
      and F.A. (P<0.05) compared with young muscles. After acute damage T2-rt increased
      in otherwise healthy young muscles with a peak at day 3, followed by a
      progressive decrease to basal values. F.A. dropped 24 hours after injury and
      afterward increased above the basal level in the regenerated muscle (from day 7
      to day 15) returning to the basal value at the end of the follow up period. The
      ADC displayed opposite kinetics. T2-rt positively correlated with the number of
      infiltrating leucocytes retrieved by immunomagnetic bead sorting from the tissue
      (r = 0.92) and with the damage/infiltration score (r = 0.88) while F.A.
      correlated with the extent of tissue regeneration evaluated at various time
      points after injury (r = 0.88). Our results indicate that multiparametric MRI is
      a sensitive and informative tool for monitoring inflammatory and structural
      muscle changes in living experimental animals; particularly, it allows
      identifying the increase of T2-rt and F.A. as common events reflecting
      inflammatory infiltration and muscle regeneration in the transient response of
      the tissue to acute injury and in the persistent adaptation to aging.

PMID- 23555017
TI  - C-reactive protein/albumin ratio predicts 90-day mortality of septic patients.
AB  - INTRODUCTION: Residual inflammation at ICU discharge may have impact upon long
      term mortality. However, the significance of ongoing inflammation on mortality
      after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are
      measured frequently in the ICU and exhibit opposing patterns during inflammation.
      Since infection is a potent trigger of inflammation, we hypothesized that CRP
      levels at discharge would correlate with long-term mortality in septic patients
      and that the CRP/albumin ratio would be a better marker of prognosis than CRP
      alone. METHODS: We evaluated 334 patients admitted to the ICU as a result of
      severe sepsis or septic shock who were discharged alive after a minimum of 72
      hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to
      predict mortality at 90 days after ICU discharge. Two multivariate logistic
      models were generated based on measurements at discharge: one model included CRP
      (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin).
      RESULTS: There were 229 (67%) and 111 (33%) patients with severe sepsis and
      septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients
      died. CRP/albumin ratios at admission and at discharge were associated with a
      poor outcome and showed greater accuracy than CRP alone at these time points (p =
      0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were
      independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95%
      CI 1.14-4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10-4.67, p
      = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP
      was not calibrated. CONCLUSIONS: Residual inflammation at ICU discharge assessed
      using the CRP/albumin ratio is an independent risk factor for mortality at 90
      days in septic patients. The use of the CRP/albumin ratio as a long-term marker
      of prognosis provides more consistent results than standard CRP values alone.

PMID- 23555018
TI  - Three groups in the 28 joints for rheumatoid arthritis synovitis--analysis using
      more than 17,000 assessments in the KURAMA database.
AB  - Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three
      composite indices evaluating the same 28 joints are commonly used for the
      evaluation of RA activity. However, the relationship between, and the frequency
      of, the joint involvements are still not fully understood. Here, we obtained and
      analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to
      2011 from electronic clinical chart templates stored in the KURAMA (Kyoto
      University Rheumatoid Arthritis Management Alliance) database. Affected rates for
      swelling and tenderness were assessed for each of the 28 joints and compared
      between two different sets of RA patients. Correlations of joint symptoms were
      analyzed for swellings and tenderness using kappa coefficient and eigen vectors
      by principal component analysis. As a result, we found that joint affected rates
      greatly varied from joint to joint both for tenderness and swelling for the two
      sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness
      and swellings are well correlated in the same joints except for the shoulder
      joints. Patients with RA tended to demonstrate right-dominant joint involvement
      and joint destruction. We also found that RA synovitis could be classified into
      three categories of joints in the correlation analyses: large joints with wrist
      joints, PIP joints, and MCP joints. Clustering analysis based on distribution of
      synovitis revealed that patients with RA could be classified into six subgroups.
      We confirmed the symmetric joint involvement in RA. Our results suggested that RA
      synovitis can be classified into subgroups and that several different mechanisms
      may underlie the pathophysiology in RA synovitis.

PMID- 23555019
TI  - CYP2C19 phenotype, stent thrombosis, myocardial infarction, and mortality in
      patients with coronary stent placement in a Chinese population.
AB  - BACKGROUND: Several studies have indicated that CYP2C19 loss-of-function
      polymorphisms have a higher risk of stent thrombosis (ST) after percutaneous
      coronary interventions (PCIs). However, this association has not been
      investigated thoroughly in a Chinese population. In this study, we aimed to
      determine the effect of CYP2C19*2 and CYP2C19*3 loss-of-function polymorphisms on
      the occurrence of ST and other adverse clinical events in a Chinese population.
      METHODS: We designed a cohort study among 1068 consecutive patients undergoing
      intracoronary stent implantation after preloading with 600 mg of clopidogrel.
      CYP2C19*2 and CYP2C19*3 were genotyped by using polymerase chain reaction
      restriction fragment length polymorphism analysis. The adverse clinical events
      recorded were ST, death, myocardial infarction (MI), and bleeding events. The
      primary end point of the study was the incidence of cumulative ST within 1 year
      after PCI. The secondary end point was other adverse clinical outcomes 1 year
      after the procedure. RESULTS: The cumulative 1-year incidence of ST was 0.88% in
      patients with extensive metabolizers (EMs) (CYP2C19*1/*1 genotype), 4.67% in
      patients with intermediate metabolizers (IMs) (CYP2C19*1/*2 or *1/*3 genotype),
      and 10.0% in patients with poor metabolizers (PMs) (CYP2C19*2/*2, *2/*3, or *3/*3
      genotype) (P<0.001). The one-year event-free survival was 97.8% in patients with
      EMs, 96.5% in patients with IMs, and 92.0% in patients with PMs (P = 0.014).
      Multivariate analysis confirmed the independent association of CYP2C19 loss-of
      function allele carriage with ST (P = 0.009) and total mortality (P<0.05).
      CONCLUSION: PM patients had an increased risk of ST, death, and MI after coronary
      stent placement in a Chinese population.

PMID- 23555020
TI  - Dynamic neural network of insight: a functional magnetic resonance imaging study
      on solving Chinese 'chengyu' riddles.
AB  - The key components of insight include breaking mental sets and forming the novel,
      task-related associations. The majority of researchers have agreed that the
      anterior cingulate cortex may mediate processes of breaking one's mental set,
      while the exact neural correlates of forming novel associations are still
      debatable. In the present study, we used a paradigm of answer selection to
      explore brain activations of insight by using event-related functional magnetic
      resonance imaging during solving Chinese 'chengyu' (in Chinese pinyin) riddles.
      Based on the participant's choice, the trials were classified into the insight
      and non-insight conditions. Both stimulus-locked and response-locked analyses are
      conducted to detect the neural activity corresponding to the early and late
      periods of insight solution, respectively. Our data indicate that the early
      period of insight solution shows more activation in the middle temporal gyrus,
      the middle frontal gyrus and the anterior cingulate cortex. These activities
      might be associated to the extensive semantic processing, as well as detecting
      and resolving cognitive conflicts. In contrast, the late period of insight
      solution produced increased activities in the hippocampus and the amygdala,
      possibly reflecting the forming of novel association and the concomitant "Aha"
      feeling. Our study supports the key role of hippocampus in forming novel
      associations, and indicates a dynamic neural network during insight solution.

PMID- 23555021
TI  - CD106 identifies a subpopulation of mesenchymal stem cells with unique
      immunomodulatory properties.
AB  - Mesenchymal stem cells (MSCs) reside in almost all of the body tissues, where
      they undergo self-renewal and multi-lineage differentiation. MSCs derived from
      different tissues share many similarities but also show some differences in term
      of biological properties. We aim to search for significant differences among
      various sources of MSCs and to explore their implications in physiopathology and
      clinical translation. We compared the phenotype and biological properties among
      different MSCs isolated from human term placental chorionic villi (CV), umbilical
      cord (UC), adult bone marrow (BM) and adipose (AD). We found that CD106 (VCAM-1)
      was expressed highest on the CV-MSCs, moderately on BM-MSCs, lightly on UC-MSCs
      and absent on AD-MSCs. CV-MSCs also showed unique immune-associated gene
      expression and immunomodulation. We thus separated CD106(+)cells and CD106(
      )cells from CV-MSCs and compared their biological activities. Both two
      subpopulations were capable of osteogenic and adipogenic differentiation while
      CD106(+)CV-MSCs were more effective to modulate T helper subsets but possessed
      decreased colony formation capacity. In addition, CD106(+)CV-MSCs expressed more
      cytokines than CD106(-)CV-MSCs. These data demonstrate that CD106 identifies a
      subpopulation of CV-MSCs with unique immunoregulatory activity and reveal a
      previously unrecognized mechanism underlying immunomodulation of MSCs.

PMID- 23555022
TI  - Concerted evolution in the ribosomal RNA cistron.
AB  - BACKGROUND: Gene conversion is the mechanism proposed to be responsible for the
      homogenization of multigene families such as the nuclear ribosomal gene clusters.
      This concerted evolutionary process prevents individual genes in gene clusters
      from accumulating mutations. The mechanism responsible for concerted evolution is
      not well understood but recombination during meiosis has been hypothesized to
      play a significant role in this homogenization. In this study we tested the
      hypothesis of unequal crossing over playing a significant role in gene conversion
      events within the ribosomal RNA cistron during meiosis, mitosis or both life
      stages in the fungal tree pathogen Ceratocystis manginecans. METHODS:
      Ceratocystis manginecans, a haploid ascomycete, reproduces homothallically and
      was found to have two distinct sequences within the internally transcribed spacer
      (ITS) region of the ribosomal RNA cistron. The different ITS types were scored
      using PCR-RFLP assays and chi-square analyses to determine the level of
      significance of the changes in the ratios of the ITS types. RESULTS: The relative
      ratios of the two ITS sequence types changed when the fungal isolates were
      cultured vegetatively or allowed to produced sexual structures and spores. These
      active changes were shown to occur more frequently during meiosis than mitosis.
      CONCLUSION: The evidence presented provides concrete support for homogenization
      in the rRNA gene clusters found in this fungus and that the most reasonable
      explanation for this process is unequal crossing over.

PMID- 23555023
TI  - A Dictyostelium secreted factor requires a PTEN-like phosphatase to slow
      proliferation and induce chemorepulsion.
AB  - In Dictyostelium discoideum, AprA and CfaD are secreted proteins that inhibit
      cell proliferation. We found that the proliferation of cells lacking CnrN, a
      phosphatase and tensin homolog (PTEN)-like phosphatase, is not inhibited by
      exogenous AprA and is increased by exogenous CfaD. The expression of CnrN in cnrN
      cells partially rescues these altered sensitivities, suggesting that CnrN is
      necessary for the ability of AprA and CfaD to inhibit proliferation. Cells
      lacking CnrN accumulate normal levels of AprA and CfaD. Like cells lacking AprA
      and CfaD, cnrN cells proliferate faster and reach a higher maximum cell density
      than wild type cells, tend to be multinucleate, accumulate normal levels of mass
      and protein per nucleus, and form less viable spores. When cnrN cells expressing
      myc-tagged CnrN are stimulated with a mixture of rAprA and rCfaD, levels of
      membrane-associated myc-CnrN increase. AprA also causes chemorepulsion of
      Dictyostelium cells, and CnrN is required for this process. Combined, these
      results suggest that CnrN functions in a signal transduction pathway downstream
      of AprA and CfaD mediating some, but not all, of the effects of AprA and CfaD.

PMID- 23555024
TI  - Discrepant fibrinolytic response in plasma and whole blood during experimental
      endotoxemia in healthy volunteers.
AB  - BACKGROUND: Sepsis induces early activation of coagulation and fibrinolysis
      followed by late fibrinolytic shutdown and progressive endothelial damage. The
      aim of the present study was to investigate and compare the functional hemostatic
      response in whole blood and plasma during experimental human endotoxemia by the
      platelet function analyzer, Multiplate and by standard and modified
      thrombelastography (TEG). METHODS: Prospective physiologic study of nine healthy
      male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli
      lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4
      h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG
      (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG+/-tissue
      type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest,
      COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations
      were applied. RESULTS: Endotoxemia induced acute SIRS with increased HR,
      temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also
      induced a hemostatic response with platelet consumption and reduced APTT while
      INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05),
      whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore,
      during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time
      (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049).
      After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In
      contrast to findings in whole blood, the plasma fibrin clot became progressively
      more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001).
      CONCLUSIONS: Endotoxemia induced a hemostatic response with reduced primary but
      enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen
      consumption followed by downregulation of fibrinolysis, with a discrepant
      fibrinolytic response in plasma and whole blood. The finding that blood cells are
      critically involved in the vasculo-fibrinolytic response to acute inflammation is
      important given that disturbances in the vascular system contribute significantly
      to morbidity and mortality in critically ill patients.

PMID- 23555025
TI  - Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases pro
      inflammatory cytokines in human dendritic cells challenged with Salmonella typhi
      through TLR activation.
AB  - Dendritic cells (DCs) constitute the first point of contact between gut
      commensals and our immune system. Despite growing evidence of the
      immunomodulatory effects of probiotics, the interactions between the cells of the
      intestinal immune system and bacteria remain largely unknown. Indeed,, the aim of
      this work was to determine whether the probiotic Bifidobacterium breve CNCM I
      4035 and its cell-free culture supernatant (CFS) have immunomodulatory effects in
      human intestinal-like dendritic cells (DCs) and how they respond to the
      pathogenic bacterium Salmonella enterica serovar Typhi, and also to elucidate the
      molecular mechanisms involved in these interactions. Human DCs were directly
      challenged with B. breve/CFS, S. typhi or a combination of these stimuli for 4 h.
      The expression pattern of genes involved in Toll-like receptor (TLR) signaling
      pathway and cytokine secretion was analyzed. CFS decreased pro-inflammatory
      cytokines and chemokines in human intestinal DCs challenged with S. typhi. In
      contrast, the B. breve CNCM I-4035 probiotic strain was a potent inducer of the
      pro-inflammatory cytokines and chemokines tested, i.e., TNF-alpha, IL-8 and
      RANTES, as well as anti-inflammatory cytokines including IL-10. CFS restored TGF
      beta levels in the presence of Salmonella. Live B.breve and its supernatant
      enhanced innate immune responses by the activation of TLR signaling pathway.
      These treatments upregulated TLR9 gene transcription. In addition, CFS was a more
      potent inducer of TLR9 expression than the probiotic bacteria in the presence of
      S. typhi. Expression levels of CASP8 and IRAK4 were also increased by CFS, and
      both treatments induced TOLLIP gene expression. Our results indicate that the
      probiotic strain B. breve CNCM I-4035 affects the intestinal immune response,
      whereas its supernatant exerts anti-inflammatory effects mediated by DCs. This
      supernatant may protect immune system from highly infectious agents such as
      Salmonella typhi and can down-regulate pro-inflammatory pathways.

PMID- 23555026
TI  - The Akt inhibitor ISC-4 synergizes with cetuximab in 5-FU-resistant colon cancer.
AB  - Phenylbutyl isoselenocyanate (ISC-4) is an Akt inhibitor with demonstrated
      preclinical efficacy against melanoma and colon cancer. In this study, we sought
      to improve the clinical utility of ISC-4 by identifying a synergistic combination
      with FDA-approved anti-cancer therapies, a relevant and appropriate disease
      setting for testing, and biomarkers of response. We tested the activity of ISC-4
      and 19 FDA-approved anticancer agents, alone or in combination, against the SW480
      and RKO human colon cancer cell lines. A synergistic interaction with cetuximab
      was identified and validated in a panel of additional colon cancer cell lines, as
      well as the kinetics of synergy. ISC-4 in combination with cetuximab
      synergistically reduced the viability of human colon cancer cells with wild-type
      but not mutant KRAS genes. Further analysis revealed that the combination therapy
      cooperatively decreased cell cycle progression, increased caspase-dependent
      apoptosis, and decreased phospho-Akt in responsive tumor cells. The synergism
      between ISC-4 and cetuximab was retained independently of acquired resistance to
      5-FU in human colon cancer cells. The combination demonstrated synergistic anti
      tumor effects in vivo without toxicity and in the face of resistance to 5-FU.
      These results suggest that combining ISC-4 and cetuximab should be explored in
      patients with 5-FU-resistant colon cancer harboring wild-type KRAS.

PMID- 23555027
TI  - Characteristics of myeloid differentiation and maturation pathway derived from
      human hematopoietic stem cells exposed to different linear energy transfer
      radiation types.
AB  - Exposure of hematopoietic stem/progenitor cells (HSPCs) to ionizing radiation
      causes a marked suppression of mature functional blood cell production in a
      linear energy transfer (LET)- and/or dose-dependent manner. However, little
      information about LET effects on the proliferation and differentiation of HSPCs
      has been reported. With the aim of characterizing the effects of different types
      of LET radiations on human myeloid hematopoiesis, in vitro hematopoiesis in Human
      CD34(+) cells exposed to carbon-ion beams or X-rays was compared. Highly purified
      CD34(+) cells exposed to each form of radiation were plated onto semi-solid
      culture for a myeloid progenitor assay. The surviving fractions of total myeloid
      progenitors, colony-forming cells (CFC), exposed to carbon-ion beams were
      significantly lower than of those exposed to X-rays, indicating that CFCs are
      more sensitive to carbon-ion beams (D(0) = 0.65) than to X-rays (D(0) = 1.07).
      Similar sensitivities were observed in granulocyte-macrophage and erythroid
      progenitors, respectively. However, the sensitivities of mixed-type progenitors
      to both radiation types were similar. In liquid culture for 14 days, no
      significant difference in total numbers of mononuclear cells was observed between
      non-irradiated control culture and cells exposed to 0.5 Gy X-rays, whereas 0.5 Gy
      carbon-ion beams suppressed cell proliferation to 4.9% of the control, a level
      similar to that for cells exposed to 1.5 Gy X-rays. Cell surface antigens
      associated with terminal maturation, such as CD13, CD14, and CD15, on harvest
      from the culture of X-ray-exposed cells were almost the same as those from the
      non-irradiated control culture. X-rays increased the CD235a(+) erythroid-related
      fraction, whereas carbon-ion beams increased the CD34(+)CD38(-) primitive cell
      fraction and the CD13(+)CD14(+/-)CD15(-) fraction. These results suggest that
      carbon-ion beams inflict severe damage on the clonal growth of myeloid HSPCs,
      although the intensity of cell surface antigen expression by mature myeloid cells
      derived from HSPCs exposed to each type of radiation was similar to that by
      controls.

PMID- 23555028
TI  - Interactions between urinary 4-tert-octylphenol levels and metabolism enzyme gene
      variants on idiopathic male infertility.
AB  - Octylphenol (OP) and Trichlorophenol (TCP) act as endocrine disruptors and have
      effects on male reproductive function. We studied the interactions between 4-tert
      Octylphenol (4-t-OP), 4-n- Octylphenol (4-n-OP), 2,3,4-Trichlorophenol (2,3,4
      TCP), 2,4,5-Trichlorophenol (2,4,5-TCP) urinary exposure levels and polymorphisms
      in selected xenobiotic metabolism enzyme genes among 589 idiopathic male
      infertile patients and 396 controls in a Han-Chinese population. Ultra high
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used
      to measure alkylphenols and chlorophenols in urine. Polymorphisms were genotyped
      using the SNPstream platform and the Taqman method. Among four phenols that were
      detected, we found that only exposure to 4-t-OP increased the risk of male
      infertility (P(trend) = 1.70*10(-7)). The strongest interaction was between 4-t
      OP and rs4918758 in CYP2C9 (P(inter) = 6.05*10(-7)). It presented a significant
      monotonic increase in risk estimates for male infertility with increasing 4-t-OP
      exposure levels among men with TC/CC genotype (low level compared with non
      exposed, odds ratio (OR) = 2.26, 95% confidence intervals (CI) = 1.06, 4.83; high
      level compared with non-exposed, OR = 9.22, 95% CI = 2.78, 30.59), but no
      associations observed among men with TT genotype. We also found interactions
      between 4-t-OP and rs4986894 in CYP2C19, and between rs1048943 in CYP1A1, on male
      infertile risk (P(inter) = 8.09*10(-7), P(inter) = 3.73*10(-4), respectively).We
      observed notable interactions between 4-t-OP exposure and metabolism enzyme gene
      polymorphisms on idiopathic infertility in Han-Chinese men.

PMID- 23555029
TI  - Nicotine affects bone resorption and suppresses the expression of cathepsin K,
      MMP-9 and vacuolar-type H(+)-ATPase d2 and actin organization in osteoclasts.
AB  - Tobacco smoking is an important risk factor for the development of several
      cancers, osteoporosis, and inflammatory diseases such as periodontitis. Nicotine
      is one of the major components of tobacco. In previous study, we showed that
      nicotine inhibits mineralized nodule formation by osteoblasts, and the culture
      medium from osteoblasts containing nicotine and lipopolysaccharide increases
      osteoclast differentiation. However, the direct effect of nicotine on the
      differentiation and function of osteoclasts is poorly understood. Thus, we
      examined the direct effects of nicotine on the expression of nicotine receptors
      and bone resorption-related enzymes, mineral resorption, actin organization, and
      bone resorption using RAW264.7 cells and bone marrow cells as osteoclast
      precursors. Cells were cultured with 10(-5), 10(-4), or 10(-3) M nicotine and/or
      50 uM alpha-bungarotoxin (btx), an 7 nicotine receptor antagonist, in
      differentiation medium containing the soluble RANKL for up 7 days. 1-5, 7, 9, and
      10 nicotine receptors were expressed on RAW264.7 cells. The expression of 7
      nicotine receptor was increased by the addition of nicotine. Nicotine suppressed
      the number of tartrate-resistant acid phosphatase positive multinuclear
      osteoclasts with large nuclei(>=10 nuclei), and decreased the planar area of each
      cell. Nicotine decreased expression of cathepsin K, MMP-9, and V-ATPase d2. Btx
      inhibited nicotine effects. Nicotine increased CA II expression although
      decreased the expression of V-ATPase d2 and the distribution of F-actin. Nicotine
      suppressed the planar area of resorption pit by osteoclasts, but did not affect
      mineral resorption. These results suggest that nicotine increased the number of
      osteoclasts with small nuclei, but suppressed the number of osteoclasts with
      large nuclei. Moreover, nicotine reduced the planar area of resorption pit by
      suppressing the number of osteoclasts with large nuclei, V-ATPase d2, cathepsin K
      and MMP-9 expression and actin organization.

PMID- 23555030
TI  - Receiving palliative treatment moderates the effect of age and gender on
      demoralization in patients with cancer.
AB  - BACKGROUND: Existential distress is an important factor affecting psychological
      well-being in cancer patients. We studied occurrence and predictors of
      demoralization, a syndrome of existential distress, in particular the interaction
      of age, gender, and curative vs. palliative treatment phase. METHODS: A cross
      sectional sample of N = 750 patients with different tumor sites was recruited
      from in- and outpatient treatment facilities. Patients completed the following
      self-report questionnaires: Demoralization Scale, Patient Health Questionnaire-9,
      Illness-Specific Social Support Scale Short Version-8, and physical problems list
      of the NCCN Distress Thermometer. Moderated multiple regression analyses were
      conducted. RESULTS: We found high demoralization in 15% and moderate
      demoralization in 8% of the sample. Curative vs. palliative treatment phase
      moderated the impact of age and gender on demoralization (three-way interaction:
      b = 1.30, P = .02): the effect of age on demoralization was negative for women
      receiving palliative treatment (b = -.26, P = .02) and positive for men receiving
      palliative treatment (b = .25, P = .03). Effects of age and gender were not
      significant among patients receiving curative treatment. Female gender was
      associated with higher demoralization among younger patients receiving palliative
      treatment only. Analyses were controlled for significant effects of the number of
      physical problems (b = 6.10, P<.001) and social support (b = -3.17, P<.001).
      CONCLUSIONS: Existential distress in terms of demoralization is a relevant
      problem within the spectrum of cancer-related distress. It is associated with a
      complex interaction of demographic and medical patient characteristics;
      existential challenges related to palliative treatment may exacerbate the impact
      of age- and gender-related vulnerability factors on demoralization. Psychosocial
      interventions should acknowledge this interaction in order to address the
      individual nature of existential distress in subgroups of cancer patients.

PMID- 23555031
TI  - Elevational gradient of vascular plant species richness and endemism in Crete-
      the effect of post-isolation mountain uplift on a continental island system.
AB  - Understanding diversity patterns along environmental gradients and their
      underlying mechanisms is a major topic in current biodiversity research. In this
      study, we investigate for the first time elevational patterns of vascular plant
      species richness and endemism on a long-isolated continental island (Crete) that
      has experienced extensive post-isolation mountain uplift. We used all available
      data on distribution and elevational ranges of the Cretan plants to interpolate
      their presence between minimum and maximum elevations in 100-m elevational
      intervals, along the entire elevational gradient of Crete (0-2400 m). We evaluate
      the influence of elevation, area, mid-domain effect, elevational Rapoport effect
      and the post-isolation mountain uplift on plant species richness and endemism
      elevational patterns. Furthermore, we test the influence of the island condition
      and the post-isolation mountain uplift to the elevational range sizes of the
      Cretan plants, using the Peloponnese as a continental control area. Total species
      richness monotonically decreases with increasing elevation, while endemic species
      richness has a unimodal response to elevation showing a peak at mid-elevation
      intervals. Area alone explains a significant amount of variation in species
      richness along the elevational gradient. Mid-domain effect is not the underlying
      mechanism of the elevational gradient of plant species richness in Crete, and
      Rapoport's rule only partly explains the observed patterns. Our results are
      largely congruent with the post-isolation uplift of the Cretan mountains and
      their colonization mainly by the available lowland vascular plant species, as
      high-elevation specialists are almost lacking from the Cretan flora. The increase
      in the proportion of Cretan endemics with increasing elevation can only be
      regarded as a result of diversification processes towards Cretan mountains
      (especially mid-elevation areas), supported by elevation-driven ecological
      isolation. Cretan plants have experienced elevational range expansion compared to
      the continental control area, as a result of ecological release triggered by
      increased species impoverishment with increasing elevation.

PMID- 23555032
TI  - Genomic comparison between Salmonella Gallinarum and Pullorum: differential
      pseudogene formation under common host restriction.
AB  - BACKGROUND: Salmonella serovars Enteritidis and Gallinarum are closely related,
      but their host ranges are very different: the former is host-promiscuous and the
      latter can infect poultry only. Comparison of their genomic sequences reveals
      that Gallinarum has undergone much more extensive degradation than Enteritidis.
      This phenomenon has also been observed in other host restricted Salmonella
      serovars, such as Typhi and Paratyphi A. The serovar Gallinarum can be further
      split into two biovars: Gallinarum and Pullorum, which take poultry as their
      common host but cause distinct diseases, with the former eliciting typhoid and
      the latter being a dysentery agent. Genomic comparison of the two pathogens, with
      a focus on pseudogenes, would provide insights into the evolutionary processes
      that might have facilitated the formation of host-restricted Salmonella
      pathogens. METHODOLOGIES/PRINCIPAL FINDINGS: We sequenced the complete genome of
      Pullorum strains and made comparison with Gallinarum and other Salmonella
      lineages. The gene contents of Gallinarum and Pullorum were highly similar, but
      their pseudogene compositions differed considerably. About one fourth of
      pseudogenes had the same inactivation mutations in Gallinarum and Pullorum but
      these genes remained intact in Enteritidis, suggesting that the ancestral
      Gallinarum may have already been restricted to poultry. On the other hand, the
      remaining pseudogenes were either in the same genes but with different
      inactivation sites or unique to Gallinarum or Pullorum, reflecting unnecessary
      functions in infecting poultry. CONCLUSIONS: Our results support the hypothesis
      that the divergence between Gallinarum and Pullorum was initiated and facilitated
      by host restriction. Formation of pseudogenes instead of gene deletion is the
      major form of genomic degradation. Given the short divergence history of
      Gallinarum and Pullorum, the effect of host restriction on genomic degradation is
      huge and rapid, and such effect seems to be continuing to work. The pseudogenes
      may reflect the unnecessary functions for Salmonella within the poultry host.

PMID- 23555033
TI  - Fission yeast CSL proteins function as transcription factors.
AB  - BACKGROUND: Transcription factors of the CSL (CBF1/RBP-Jk/Suppressor of
      Hairless/LAG-1) family are key regulators of metazoan development and function as
      the effector components of the Notch receptor signalling pathway implicated in
      various cell fate decisions. CSL proteins recognize specifically the GTG[G/A]AA
      sequence motif and several mutants compromised in their ability to bind DNA have
      been reported. In our previous studies we have identified a number of novel
      putative CSL family members in fungi, organisms lacking the Notch pathway. It is
      not clear whether these represent genuine CSL family members.
      METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of in vitro and in vivo
      approaches we characterized the DNA binding properties of Cbf11 and Cbf12, the
      antagonistic CSL paralogs from the fission yeast, important for the proper
      coordination of cell cycle events and the regulation of cell adhesion. We have
      shown that a mutation of a conserved arginine residue abolishes DNA binding in
      both CSL paralogs, similar to the situation in mouse. We have also demonstrated
      the ability of Cbf11 and Cbf12 to activate gene expression in an autologous
      fission yeast reporter system. CONCLUSIONS/SIGNIFICANCE: Our results indicate
      that the fission yeast CSL proteins are indeed genuine family members capable of
      functioning as transcription factors, and provide support for the ancient
      evolutionary origin of this important protein family.

PMID- 23555034
TI  - Sex and the syndrome: individual and population consistency in behaviour in rock
      pool prawn Palaemon elegans.
AB  - Animal personality has been widely documented across a range of species. The
      concept of personality is composed of individual behavioural consistency across
      time and between situations, and also behavioural trait correlations known as
      behavioural syndromes. Whilst many studies have now investigated the stability of
      individual personality traits, few have analysed the stability over time of
      entire behavioural syndromes. Here we present data from a behavioural study of
      rock pool prawns. We show that prawns are temporally consistent in a range of
      behaviours, including activity, exploration and boldness, and also that a
      behavioural syndrome is evident in this population. We find correlations between
      many behavioural traits (activity, boldness, shoaling and exploration). In
      addition, behavioural syndrome structure was consistent over time. Finally, few
      studies have explicitly studied the role of sex differences in personality
      traits, behavioural consistency and syndrome structure. We report behavioural
      differences between male and female prawns but no differences in patterns of
      consistency. Our study adds to the growing literature on animal personality, and
      provides evidence showing that syndromes themselves can exhibit temporal
      consistency.

PMID- 23555035
TI  - Predictive factors of plasma HIV suppression during pregnancy: a prospective
      cohort study in Benin.
AB  - OBJECTIVE: To investigate the factors associated with HIV1 RNA plasma viral load
      (pVL) below 40 copies/mL at the third trimester of pregnancy, as part of
      prevention of mother-to-child transmission (PMTCT) in Benin. DESIGN: Sub study of
      the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women,
      conducted before and after the implementation of the WHO 2009 revised guidelines
      for PMTCT. METHODS: HIV-infected women were enrolled in the second trimester of
      pregnancy. Socio-economic characteristics, HIV history, clinical and biological
      characteristics were recorded. Malaria prevention and PMTCT involving
      antiretroviral therapy (ART) for mothers and infants were provided. Logistic
      regression helped identifying factors associated with virologic suppression at
      the end of pregnancy. RESULTS: Overall 217 third trimester pVLs were available,
      and 71% showed undetectability. Virologic suppression was more frequent in women
      enrolled after the change in PMTCT recommendations, advising to start ART at 14
      weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic
      group (the predominant ethnic group in the study area), regular job, first and
      second pregnancy, higher baseline pVL and impaired adherence to ART were negative
      factors whereas higher weight, higher antenatal care attendance and longer ART
      duration were favorable factors to achieve virologic suppression. CONCLUSIONS:
      This study provides more evidence that ART has to be initiated before the last
      trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin,
      new recommendations supporting early initiation were well implemented and,
      together with a high antenatal care attendance, led to high rate of virologic
      control.

PMID- 23555036
TI  - Soluble and membrane-bound TGF-beta-mediated regulation of intratumoral T cell
      differentiation and function in B-cell non-Hodgkin lymphoma.
AB  - While the effect of TGF-beta on malignant B cells in non-Hodgkin lymphoma (NHL)
      has been previously evaluated, studies to specifically define the role of TGF
      beta in tumor immunity in B-cell NHL are limited. We found that soluble TGF-beta,
      secreted by both lymphoma cells and intratumoral T cells, is present in the serum
      of patients with B-cell NHL. Soluble TGF-beta promoted regulatory T (T(reg))
      cells by enhancing expression of Foxp3 in CD4(+) T cells and suppressed effector
      helper T (T(H)) cells by inhibiting expression of IFN-gamma and IL-17. Blockade
      of the IL-2 signaling pathway diminished the effect of soluble TGF-beta on T cell
      differentiation. Furthermore, we found that membrane-bound TGF-beta is expressed
      specifically on the surface of malignant B cells in B-cell NHL. TGF-beta was able
      to bind to the surface of lymphoma B cells through an interaction with heparan
      sulfate (HS) but not through the TGF-beta receptor. We showed that pretreatment
      of lymphoma B cells with TGF-beta significantly inhibits the proliferation and
      cytokine production of intratumoral T cells. Taken together, these results
      suggest that tumor-associated soluble and membrane-bound TGF-beta are involved in
      the regulation of intratumoral T cell differentiation and function in B-cell NHL.

PMID- 23555037
TI  - The effects of visual control and distance in modulating peripersonal spatial
      representation.
AB  - In the presence of vision, finalized motor acts can trigger spatial remapping,
      i.e., reference frames transformations to allow for a better interaction with
      targets. However, it is yet unclear how the peripersonal space is encoded and
      remapped depending on the availability of visual feedback and on the target
      position within the individual's reachable space, and which cerebral areas
      subserve such processes. Here, functional magnetic resonance imaging (fMRI) was
      used to examine neural activity while healthy young participants performed reach
      to-grasp movements with and without visual feedback and at different distances of
      the target from the effector (near to the hand-about 15 cm from the starting
      position-vs. far from the hand-about 30 cm from the starting position). Brain
      response in the superior parietal lobule bilaterally, in the right dorsal
      premotor cortex, and in the anterior part of the right inferior parietal lobule
      was significantly greater during visually-guided grasping of targets located at
      the far distance compared to grasping of targets located near to the hand. In the
      absence of visual feedback, the inferior parietal lobule exhibited a greater
      activity during grasping of targets at the near compared to the far distance.
      Results suggest that in the presence of visual feedback, a visuo-motor circuit
      integrates visuo-motor information when targets are located farther away.
      Conversely in the absence of visual feedback, encoding of space may demand
      multisensory remapping processes, even in the case of more proximal targets.

PMID- 23555038
TI  - Here today, gone tomorrow--adaptation to change in memory-guided visual search.
AB  - Visual search for a target object can be facilitated by the repeated presentation
      of an invariant configuration of nontargets ('contextual cueing'). Here, we
      tested adaptation of learned contextual associations after a sudden, but
      permanent, relocation of the target. After an initial learning phase targets were
      relocated within their invariant contexts and repeatedly presented at new
      locations, before they returned to the initial locations. Contextual cueing for
      relocated targets was neither observed after numerous presentations nor after
      insertion of an overnight break. Further experiments investigated whether
      learning of additional, previously unseen context-target configurations is
      comparable to adaptation of existing contextual associations to change. In
      contrast to the lack of adaptation to changed target locations, contextual cueing
      developed for additional invariant configurations under identical training
      conditions. Moreover, across all experiments, presenting relocated targets or
      additional contexts did not interfere with contextual cueing of initially learned
      invariant configurations. Overall, the adaptation of contextual memory to changed
      target locations was severely constrained and unsuccessful in comparison to
      learning of an additional set of contexts, which suggests that contextual cueing
      facilitates search for only one repeated target location.

PMID- 23555040
TI  - Modeling the soil water retention curves of soil-gravel mixtures with regression
      method on the Loess Plateau of China.
AB  - Soil water retention parameters are critical to quantify flow and solute
      transport in vadose zone, while the presence of rock fragments remarkably
      increases their variability. Therefore a novel method for determining water
      retention parameters of soil-gravel mixtures is required. The procedure to
      generate such a model is based firstly on the determination of the quantitative
      relationship between the content of rock fragments and the effective saturation
      of soil-gravel mixtures, and then on the integration of this relationship with
      former analytical equations of water retention curves (WRCs). In order to find
      such relationships, laboratory experiments were conducted to determine WRCs of
      soil-gravel mixtures obtained with a clay loam soil mixed with shale clasts or
      pebbles in three size groups with various gravel contents. Data showed that the
      effective saturation of the soil-gravel mixtures with the same kind of gravels
      within one size group had a linear relation with gravel contents, and had a power
      relation with the bulk density of samples at any pressure head. Revised formulas
      for water retention properties of the soil-gravel mixtures are proposed to
      establish the water retention curved surface models of the power-linear functions
      and power functions. The analysis of the parameters obtained by regression and
      validation of the empirical models showed that they were acceptable by using
      either the measured data of separate gravel size group or those of all the three
      gravel size groups having a large size range. Furthermore, the regression
      parameters of the curved surfaces for the soil-gravel mixtures with a large range
      of gravel content could be determined from the water retention data of the soil
      gravel mixtures with two representative gravel contents or bulk densities. Such
      revised water retention models are potentially applicable in regional or large
      scale field investigations of significantly heterogeneous media, where various
      gravel sizes and different gravel contents are present.

PMID- 23555039
TI  - Plant and fungal diversity in gut microbiota as revealed by molecular and culture
      investigations.
AB  - BACKGROUND: Few studies describing eukaryotic communities in the human gut
      microbiota have been published. The objective of this study was to investigate
      comprehensively the repertoire of plant and fungal species in the gut microbiota
      of an obese patient. METHODOLOGY/PRINCIPAL FINDINGS: A stool specimen was
      collected from a 27-year-old Caucasian woman with a body mass index of 48.9 who
      was living in Marseille, France. Plant and fungal species were identified using a
      PCR-based method incorporating 25 primer pairs specific for each eukaryotic
      phylum and universal eukaryotic primers targeting 18S rRNA, internal transcribed
      spacer (ITS) and a chloroplast gene. The PCR products amplified using these
      primers were cloned and sequenced. Three different culture media were used to
      isolate fungi, and these cultured fungi were further identified by ITS
      sequencing. A total of 37 eukaryotic species were identified, including a Diatoms
      (Blastocystis sp.) species, 18 plant species from the Streptophyta phylum and 18
      fungal species from the Ascomycota, Basidiomycota and Chytridiocomycota phyla.
      Cultures yielded 16 fungal species, while PCR-sequencing identified 7 fungal
      species. Of these 7 species of fungi, 5 were also identified by culture. Twenty
      one eukaryotic species were discovered for the first time in human gut
      microbiota, including 8 fungi (Aspergillus flavipes, Beauveria bassiana, Isaria
      farinosa, Penicillium brevicompactum, Penicillium dipodomyicola, Penicillium
      camemberti, Climacocystis sp. and Malassezia restricta). Many fungal species
      apparently originated from food, as did 11 plant species. However, four plant
      species (Atractylodes japonica, Fibraurea tinctoria, Angelica anomala, Mitella
      nuda) are used as medicinal plants. CONCLUSIONS/SIGNIFICANCE: Investigating the
      eukaryotic components of gut microbiota may help us to understand their role in
      human health.

PMID- 23555041
TI  - Loss to follow-up as a competing risk in an observational study of HIV-1
      incidence.
AB  - OBJECTIVE: Conventional survival estimates may be biased if loss to follow-up
      (LTF) is associated with the outcome of interest. Our goal was to assess whether
      the association between sexual risk behavior and HIV-1 acquisition changed after
      accounting for LTF with competing risks regression. METHODS: HIV-1-seronegative
      women who enrolled in a Kenyan sex worker cohort from 1993-2007 were followed
      prospectively and tested for HIV at monthly clinic visits. Our primary predictor
      was self-reported sexual risk behavior in the past week, analyzed as a time
      dependent covariate. Outcomes included HIV-1 acquisition and LTF. We analyzed the
      data using Cox proportional hazards regression and competing risks regression, in
      which LTF was treated as a competing event. RESULTS: A total of 1,513 women
      contributed 4,150 person-years (py), during which 198 (13.1%) acquired HIV-1
      infection (incidence, 4.5 per 100 py) and 969 (64.0%) were LTF (incidence, 23.4
      per 100 py). After adjusting for potential confounders, women reporting
      unprotected sex with multiple partners were less likely to be lost to follow-up
      (adjusted sub-hazard ratio (aSHR) 0.50, 95% confidence interval (CI) 0.32-0.76,
      relative to no sexual activity). The risk of HIV-1 acquisition after reporting
      unprotected sex with multiple partners was similar with Cox regression (adjusted
      hazard ratio (aHR) 2.41, 95% CI 1.36-4.27) and competing risks regression (aSHR
      2.47, 95% CI 1.33-4.58). CONCLUSIONS: Unprotected sex with multiple partners was
      associated with higher HIV-1 acquisition risk, but lower attrition. This
      differential attrition did not substantially bias Cox regression estimates when
      compared to competing risks regression results.

PMID- 23555042
TI  - Regulation of intestinal immune response by selective removal of the anterior,
      posterior, or entire pituitary gland in Trichinella spiralis infected golden
      hamsters.
AB  - The influence of anterior pituitary hormones on the gastrointestinal tract of
      humans and animals has been previously reported. Hypophysectomy (HYPOX) in the
      rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion
      and intestinal absorption, as well as increased susceptibility to bacterial and
      viral infections. However, to our knowledge, no findings have been published
      concerning the immune response following HYPOX during worm infection,
      particularly that which is caused by the nematode Trichinella spiralis. The aim
      of this work was to analyze the effects of total or partial HYPOX on colonization
      of T. spiralis in the intestinal lumen, together with duodenal and splenic
      cytokine expression. Our results indicate that 5 days post infection, only
      neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally
      recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser
      confocal microscopy, we observed that the mean intensity of all tested Th1
      cytokines was markedly diminished, even in the duodenum of infected controls. In
      contrast, a high level of expression of these cytokines was noted in the NIL
      infected hamsters. Likewise, a significant decrease in the fluorescence intensity
      of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of
      control and sham infected hamsters, compared to animals with NIL surgeries, which
      showed an increase in the expression of IL-5 and IL-13. Histology of duodenal
      mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located
      along the lamina propria, which was related to the presence of the parasite. We
      conclude that hormones from each pituitary lobe affect the gastrointestinal
      immune responses to T. spiralis through various mechanisms.

PMID- 23555044
TI  - Association between virulence and triazole tolerance in the phytopathogenic
      fungus Mycosphaerella graminicola.
AB  - Host resistance and synthetic antimicrobials such as fungicides are two of the
      main approaches used to control plant diseases in conventional agriculture.
      Although pathogens often evolve to overcome host resistance and antimicrobials,
      the majority of reports have involved qualitative host - pathogen interactions or
      antimicrobials targeting a single pathogen protein or metabolic pathway. Studies
      that consider jointly the evolution of virulence, defined as the degree of damage
      caused to a host by parasite infection, and antimicrobial resistance are rare.
      Here we compared virulence and fungicide tolerance in the fungal pathogen
      Mycosphaerella graminicola sampled from wheat fields across three continents and
      found a positive correlation between virulence and tolerance to a triazole
      fungicide. We also found that quantitative host resistance selected for higher
      pathogen virulence. The possible mechanisms responsible for these observations
      and their consequences for sustainable disease management are discussed.

PMID- 23555043
TI  - Multidisciplinary team-based approach for comprehensive preoperative pulmonary
      rehabilitation including intensive nutritional support for lung cancer patients.
AB  - BACKGROUND: To decrease the risk of postoperative complication, improving general
      and pulmonary conditioning preoperatively should be considered essential for
      patients scheduled to undergo lung surgery. OBJECTIVE: The aim of this study is
      to develop a short-term beneficial program of preoperative pulmonary
      rehabilitation for lung cancer patients. METHODS: From June 2009, comprehensive
      preoperative pulmonary rehabilitation (CHPR) including intensive nutritional
      support was performed prospectively using a multidisciplinary team-based
      approach. Postoperative complication rate and the transitions of pulmonary
      function in CHPR were compared with historical data of conventional preoperative
      pulmonary rehabilitation (CVPR) conducted since June 2006. The study population
      was limited to patients who underwent standard lobectomy. RESULTS: Postoperative
      complication rate in the CVPR (n = 29) and CHPR (n = 21) were 48.3% and 28.6% (p
      = 0.2428), respectively. Those in patients with Charlson Comorbidity Index scores
      >=2 were 68.8% (n = 16) and 27.3% (n = 11), respectively (p = 0.0341) and those
      in patients with preoperative risk score in Estimation of Physiologic Ability and
      Surgical Stress scores >0.3 were 57.9% (n = 19) and 21.4% (n = 14), respectively
      (p = 0.0362). Vital capacities of pre- and post intervention before surgery in
      the CHPR group were 2.63+/-0.65 L and 2.75+/-0.63 L (p = 0.0043), respectively;
      however, their transition in the CVPR group was not statistically significant (p
      = 0.6815). Forced expiratory volumes in one second of pre- and post intervention
      before surgery in the CHPR group were 1.73+/-0.46 L and 1.87+/-0.46 L (p =
      0.0012), respectively; however, their transition in the CVPR group was not
      statistically significant (p = 0.6424). CONCLUSIONS: CHPR appeared to be a
      beneficial and effective short-term preoperative rehabilitation protocol,
      especially in patients with poor preoperative conditions.

PMID- 23555045
TI  - Knockdown of HPRT for selection of genetically modified human hematopoietic
      progenitor cells.
AB  - The inability to obtain sufficient numbers of transduced cells remains a
      limitation in gene therapy. One strategy to address this limitation is in vivo
      pharmacologic selection of transduced cells. We have previously shown that
      knockdown of HPRT using lentiviral delivered shRNA facilitates efficient
      selection of transduced murine hematopoietic progenitor cells (HPC) using 6
      thioguanine (6TG). Herein, we now extend these studies to human HPC. We tested
      multiple shRNA constructs in human derived cell lines and identified the optimal
      shRNA sequence for knockdown of HPRT and 6TG resistance. We then tested this
      vector in human umbilical cord blood derived HPC in vitro and in NOD/SCID
      recipients. Knockdown of HPRT effectively provided resistance to 6TG in vitro.
      6TG treatment of mice resulted in increased percentages of transduced human
      CD45(+) cells in the peripheral blood and in the spleen in particular, in both
      myeloid and lymphoid compartments. 6TG treatment of secondary recipients resulted
      in higher percentages of transduced human cells in the bone marrow, confirming
      selection from the progeny of long-term repopulating HPCs. However, the extent of
      selection of cells in the bone marrow at the doses of 6TG tested and the toxicity
      of higher doses, suggest that this strategy may be limited to selection of more
      committed progenitor cells. Together, these data suggest that human HPC can be
      programmed to be resistant to purine analogs, but that HPRT knockdown/6TG-based
      selection may not be robust enough for in vivo selection.

PMID- 23555046
TI  - Combined RNAi-mediated suppression of Rictor and EGFR resulted in complete tumor
      regression in an orthotopic glioblastoma tumor model.
AB  - The PI3K/AKT/mTOR pathway is commonly over activated in glioblastoma (GBM), and
      Rictor was shown to be an important regulator downstream of this pathway. EGFR
      overexpression is also frequently found in GBM tumors, and both EGFR and Rictor
      are associated with increased proliferation, invasion, metastasis and poor
      prognosis. This research evaluated in vitro and in vivo whether the combined
      silencing of EGFR and Rictor would result in therapeutic benefits. The
      therapeutic potential of targeting these proteins in combination with
      conventional agents with proven activity in GBM patients was also assessed. In
      vitro validation studies were carried out using siRNA-based gene silencing
      methods in a panel of three commercially available human GBM cell lines,
      including two PTEN mutant lines (U251MG and U118MG) and one PTEN-wild type line
      (LN229). The impact of EGFR and/or Rictor silencing on cell migration and
      sensitivity to chemotherapeutic drugs in vitro was determined. In vivo validation
      of these studies was focused on EGFR and/or Rictor silencing achieved using
      doxycycline-inducible shRNA-expressing U251MG cells implanted orthotopically in
      Rag2M mice brains. Target silencing, tumor size and tumor cell proliferation were
      assessed by quantification of immunohistofluorescence-stained markers. siRNA
      mediated silencing of EGFR and Rictor reduced U251MG cell migration and increased
      sensitivity of the cells to irinotecan, temozolomide and vincristine. In LN229,
      co-silencing of EGFR and Rictor resulted in reduced cell migration, and increased
      sensitivity to vincristine and temozolomide. In U118MG, silencing of Rictor alone
      was sufficient to increase this line's sensitivity to vincristine and
      temozolomide. In vivo, while the silencing of EGFR or Rictor alone had no
      significant effect on U251MG tumor growth, silencing of EGFR and Rictor together
      resulted in a complete eradication of tumors. These data suggest that the
      combined silencing of EGFR and Rictor should be an effective means of treating
      GBM.

PMID- 23555047
TI  - Lack of PD-L1 expression by iNKT cells improves the course of influenza A
      infection.
AB  - There is evidence indicating that invariant Natural Killer T (iNKT) cells play an
      important role in defense against influenza A virus (IAV). However, the effect of
      inhibitory receptor, programmed death-1 (PD-1), and its ligands, programmed death
      ligand (PD-L) 1 and 2 on iNKT cells in protection against IAV remains to be
      elucidated. Here we investigated the effects of these co-stimulatory molecules on
      iNKT cells in the response to influenza. We discovered that compare to the wild
      type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident
      by reduced weight loss, decreased pulmonary inflammation and cellular
      infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss,
      pulmonary inflammation and cellular infiltration compare to the wild type mice
      after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1
      or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these
      findings. Interestingly, in our transfer system PD-L1(-/-)-derived iNKT cells
      produced high levels of interferon-gamma whereas PD-L2(-/-)-derived iNKT cells
      produced high amounts of interleukin-4 and 13 suggesting a role for these
      cytokines in sensitivity to influenza. We identified that PD-L1 negatively
      regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice.
      Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells
      reduces the sensitivity to IAV and that the presence of PD-L2 is important for
      dampening the deleterious inflammatory responses after IAV infection. Our
      findings potentially have clinical implications for developing new therapies for
      influenza.

PMID- 23555048
TI  - T cells contribute to stroke-induced lymphopenia in rats.
AB  - Stroke-induced immunodepression (SIID) results when T cell and non-T immune
      cells, such as B cells, NK cells and monocytes, are reduced in the peripheral
      blood and spleen after stroke. We investigated the hypothesis that T cells are
      required for the reductions in non-T cell subsets observed in SIID, and further
      examined a potential correlation between lymphopenia and High-mobility group
      protein B1 (HMGB1) release, a protein that regulates inflammation and
      immunodepression. Our results showed that focal ischemia resulted in similar
      cortical infarct sizes in both wild type (WT) Sprague Dawley (SD) rats and nude
      rats with a SD genetic background, which excludes the possibility of different
      infarct sizes affecting SIID. In addition, the numbers of CD68-positive
      macrophages in the ischemic brain did not differ between WT and nude rats.
      Numbers of total peripheral blood mononuclear cells (PBMCs) or splenocytes and
      lymphocyte subsets, including T cells, CD4(+) or CD8(+) T cells, B cells and
      monocytes in the blood and spleen, were decreased after stroke in WT rats. In
      nude rats, however, the total number of PBMCs and absolute numbers of NK cells, B
      cells and monocytes were increased in the peripheral blood after stroke; nude
      rats are athymic therefore they have few T cells present. Adoptive transfer of WT
      splenocytes into nude rats before stroke resulted in lymphopenia after stroke
      similar to WT rats. Moreover, in vitro T cell proliferation stimulated by
      Concanavalin A was significantly inhibited in WT rats as well as in nude rats
      receiving WT splenocyte adoptive transfer, suggesting that T cell function is
      indeed inhibited after stroke. Lastly, we demonstrated that stroke-induced
      lymphopenia is associated with a reduction in HMGB1 release in the peripheral
      blood. In conclusion, T cells are required for stroke-induced reductions in non-T
      immune cells and they are the most crucial lymphocytes for SIID.

PMID- 23555049
TI  - The frontal eye fields limit the capacity of visual short-term memory in rhesus
      monkeys.
AB  - The frontal eye fields (FEF) in rhesus monkeys have been implicated in visual
      short-term memory (VSTM) as well as control of visual attention. Here we examined
      the importance of the area in the VSTM capacity and the relationship between VSTM
      and attention, using the chemical inactivation technique and multi-target saccade
      tasks with or without the need of target-location memory. During FEF
      inactivation, serial saccades to targets defined by color contrast were
      unaffected, but saccades relying on short-term memory were impaired when the
      target count was at the capacity limit of VSTM. The memory impairment was
      specific to the FEF-coded retinotopic locations, and subject to competition among
      targets distributed across visual fields. These results together suggest that the
      FEF plays a crucial role during the entry of information into VSTM, by enabling
      attention deployment on targets to be remembered. In this view, the memory
      capacity results from the limited availability of attentional resources provided
      by FEF: The FEF can concurrently maintain only a limited number of activations to
      register the targets into memory. When lesions render part of the area
      unavailable for activation, the number would decrease, further reducing the
      capacity of VSTM.

PMID- 23555050
TI  - Amino Acid derivatives as new zinc binding groups for the design of selective
      matrix metalloproteinase inhibitors.
AB  - A number of matrix metalloproteinases (MMPs) are important medicinal targets for
      conditions ranging from rheumatoid arthritis to cardiomyopathy, periodontal
      disease, liver cirrhosis, multiple sclerosis, and cancer invasion and metastasis,
      where they showed to have a dual role, inhibiting or promoting important
      processes involved in the pathology. MMPs contain a zinc (II) ion in the protein
      active site. Small-molecule inhibitors of these metalloproteins are designed to
      bind directly to the active site metal ions. In an effort to devise new
      approaches to selective inhibitors, in this paper, we describe the synthesis and
      preliminary biological evaluation of amino acid derivatives as new zinc binding
      groups (ZBGs). The incorporation of selected metal-binding functions in more
      complex biphenyl sulfonamide moieties allowed the identification of one compound
      able to interact selectively with different MMP enzymatic isoforms.

PMID- 23555051
TI  - Lifestyle and dietary factors associated with the evolution of cardiometabolic
      risk over four years in West-African adults: the Benin study.
AB  - AIM: To assess in adults from Benin changes in cardiometabolic risk (CMR) using
      both the Framingham risk score (FRS) and metabolic syndrome (MetS) and to examine
      the effects of diet, and lifestyles, controlling for location and socioeconomic
      status. METHODS: Apparently healthy subjects (n = 541) aged 25-60 years and
      randomly selected in the largest city, a small town, and rural areas were
      included in the four-year longitudinal study. Along with CMR factors,
      socioeconomic, diet and lifestyle data were collected in individual interviews. A
      food score based on consumption frequency of four "sentinel" food groups (meat
      and poultry, dairy, eggs, and vegetables) was developed. Lifestyle included
      physical activity, alcohol and tobacco use. Education and income (proxy) were the
      socioeconomic variables. RESULTS: Among the subjects with four-year follow-up
      data (n = 416), 13.5% were at risk at baseline, showing MetS or FRS >= 10%. The
      incidence of MetS and FRS >= 10% during follow-up was 8.2% and 5%, respectively.
      CMR deteriorated in 21% of subjects. Diet and lifestyle mediated location and
      income effects on CMR evolution. Low food scores and inactivity increased the
      likelihood of CMR deterioration. CONCLUSION: Combining MetS and FRS might be
      appropriate for surveillance purposes in order to better capture CMR and inform
      preventive measures.

PMID- 23555052
TI  - The multicomponent anthropometric model for assessing body composition in a male
      pediatric population: a simultaneous prediction of fat mass, bone mineral
      content, and lean soft tissue.
AB  - The aim of this study was to propose and cross-validate an anthropometric model
      for the simultaneous estimation of fat mass (FM), bone mineral content (BMC), and
      lean soft tissue (LST) using DXA as the reference method. A total of 408 boys (8
      18 years) were included in this sample. Whole-body FM, BMC, and LST were measured
      by DXA and considered as dependent variables. Independent variables included
      thirty-two anthropometrics measurements and maturity offset determined by the
      Mirwald equation. From a multivariate regression model ((n)Y(m) = (n)x(r + 1)(r +
      1)beta(m) + (n)epsilon(m)), a matrix analysis was performed resulting in a
      multicomponent anthropometric model. The cross-validation was executed through
      the sum of squares of residuals (PRESS) method. Five anthropometric variables
      predicted simultaneously FM, BMC, and LST. Cross-validation parameters indicated
      that the new model is accurate with high R(PRESS)(2) values ranging from 0.94 to
      0.98 and standard error of estimate ranging from 0.01 to 0.09. The newly proposed
      model represents an alternative to accurately assess the body composition in male
      pediatric ages.

PMID- 23555053
TI  - Prevalence and Risk Factors of Anemia among Children 6-59 Months Old in Haiti.
AB  - Anemia has serious consequences on child growth, development, and survival. This
      study was conducted in Fond des Blancs and Villa, Haiti, to assess the prevalence
      of childhood anemia and its risk factors in order to inform program design.
      Children 6-59 months old (n = 557) were selected using a cross-sectional
      multistage sampling methodology. Hemoglobin was measured using the HemoCue
      technique. Descriptive and multivariate analyses were performed to determine
      prevalence and factors associated with anemia. The prevalence of childhood anemia
      was 38.8% (23.9% mild, 14.7% moderate, and 0.2% severe). Mean hemoglobin was 11.2
      +/- 1.2 g/dL. Variables associated with child anemia were age less than 24 months
      (OR = 2.6; P = 0.000), stunting (OR = 2.2; P = 0.005), and mother's low
      hemoglobin level (OR = 1.8; P = 0.011). Anemia among young children in Fond des
      Blancs and Villa is a public health problem. Predictors of child anemia in this
      region include child's age, stunting, and mother's anemia. Interventions and
      strategies aimed at addressing effectively anemia in this population must
      therefore target mothers and children under two years of age.

PMID- 23555054
TI  - Postinfantile giant cell hepatitis: an etiological and prognostic perspective.
AB  - Giant cell hepatitis is common manifestation in pediatric liver diseases, but
      quite uncommon in adults, only about 100 cases reported in the English literature
      in the last two decades. Data for the present review were identified by a
      structured PubMed/MEDLINE search from 1963 to December 2012, using keywords
      postinfantile giant cell hepatitis (PIGCH), adult giant cell hepatitis, and
      syncytial giant cell hepatitis in adults and liver. We report a case of
      postinfantile giant cell hepatitis along with the review related to the etiology
      and respective outcome, as the literature in the last 20 years suggests. This
      condition is probably due to idiosyncratic or cytopathic response of individual
      to various hepatocytic stimuli. It is purely a histomorphological diagnosis and
      does not establish the etiology. Autoimmune liver diseases are most common
      etiology, in around 40% of cases, but various viruses, drugs, posttransplant
      condition, and other causes also have been reported. Prognosis depends upon the
      etiology. In this paper, we emphasized various causative factors of PIGCH and
      their respective outcome in patients affected by them. We also highlighted the
      possible pathogenesis and histopathological spectrum of this entity on the basis
      of description given in various studies and our limited experience of few cases.

PMID- 23555055
TI  - Top-Down Characterization of the Post-Translationally Modified Intact Periplasmic
      Proteome from the Bacterium Novosphingobium aromaticivorans.
AB  - The periplasm of Gram-negative bacteria is a dynamic and physiologically
      important subcellular compartment where the constant exposure to potential
      environmental insults amplifies the need for proper protein folding and
      modifications. Top-down proteomics analysis of the periplasmic fraction at the
      intact protein level provides unrestricted characterization and annotation of the
      periplasmic proteome, including the post-translational modifications (PTMs) on
      these proteins. Here, we used single-dimension ultra-high pressure liquid
      chromatography coupled with the Fourier transform mass spectrometry (FTMS) to
      investigate the intact periplasmic proteome of Novosphingobium aromaticivorans.
      Our top-down analysis provided the confident identification of 55 proteins in the
      periplasm and characterized their PTMs including signal peptide removal, N
      terminal methionine excision, acetylation, glutathionylation, pyroglutamate, and
      disulfide bond formation. This study provides the first experimental evidence for
      the expression and periplasmic localization of many hypothetical and
      uncharacterized proteins and the first unrestrictive, large-scale data on PTMs in
      the bacterial periplasm.

PMID- 23555056
TI  - iTRAQ-Based and Label-Free Proteomics Approaches for Studies of Human Adenovirus
      Infections.
AB  - Both isobaric tags for relative and absolute quantitation (iTRAQ) and label-free
      methods are widely used for quantitative proteomics. Here, we provide a detailed
      evaluation of these proteomics approaches based on large datasets from biological
      samples. iTRAQ-label-based and label-free quantitations were compared using
      protein lysate samples from noninfected human lung epithelial A549 cells and from
      cells infected for 24 h with human adenovirus type 3 or type 5. Either iTRAQ
      label-based or label-free methods were used, and the resulting samples were
      analyzed by liquid chromatography (LC) and tandem mass spectrometry (MS/MS). To
      reduce a possible bias from quantitation software, we applied several software
      packages for each procedure. ProteinPilot and Scaffold Q+ software were used for
      iTRAQ-labeled samples, while Progenesis LC-MS and ProgenesisF-T2PQ/T3PQ were
      employed for label-free analyses. R (2) correlation coefficients correlated well
      between two software packages applied to the same datasets with values between
      0.48 and 0.78 for iTRAQ-label-based quantitations and 0.5 and 0.86 for label-free
      quantitations. Analyses of label-free samples showed higher levels of protein up-
      or downregulation in comparison to iTRAQ-labeled samples. The concentration
      differences were further evaluated by Western blotting for four downregulated
      proteins. These data suggested that the label-free method was more accurate than
      the iTRAQ method.

PMID- 23555057
TI  - Assessment of definitions of sustained disease progression in relapsing-remitting
      multiple sclerosis.
AB  - Sustained progression on the expanded disability status scale (EDSS) is a common
      outcome measure of disease progression in clinical studies of MS. Unfortunately,
      this outcome may not accurately measure long-term and irreversible disease
      progression. To assess the performance of definitions of sustained progression,
      patients with relapsing-remitting MS (RRMS) or a clinically isolated syndrome
      with evidence of lesions on a brain MRI were included in our study. Fifteen
      definitions of sustained progression using both the EDSS and the functional
      system (FS) scales were investigated. The impact of both relapses and changes in
      provider on the probability of maintaining progression was also evaluated.
      Although the provider scoring the EDSS sometimes changed during followup, the
      provider had access to previous EDSS scores. Between 15.8% and 42.2% of patients
      experienced sustained progression based on the definitions using EDSS as the
      outcome, but nearly 50% of these patients failed to maintain sustained
      progression for the duration of followup. When FS scales were used, progression
      was most common on the pyramidal and sensory scales. Unfortunately, progression
      on specific FS scales failed to be more sensitive to irreversible disability.
      Relapses or changes in provider did not explain the poor performance of the
      measures. Short-term changes in the EDSS or FS scores may not be an accurate
      marker of irreversible change in RRMS.

PMID- 23555058
TI  - Benign hepatocellular tumors in children: focal nodular hyperplasia and
      hepatocellular adenoma.
AB  - Benign liver tumors are very rare in children. Most focal nodular hyperplasia
      (FNH) remain sporadic, but predisposing factors exist, as follows: long-term
      cancer survivor (with an increasing incidence), portal deprivation in congenital
      or surgical portosystemic shunt. The aspect is atypical on imaging in two-thirds
      of cases. Biopsy of the tumor and the nontumoral liver is then required. Surgical
      resection will be discussed in the case of large tumors with or without symptoms.
      In the case of associated vascular disorder with portal deprivation, restoration
      of the portal flow will be discussed in the hope of seeing the involution of FNH.
      HepatoCellular Adenoma (HCA) is frequently associated with predisposing factors
      such as GSD type I and III, Fanconi anemia especially if androgen therapy is
      administered, CPSS, and SPSS. Adenomatosis has been reported in germline mutation
      of HNF1- alpha . Management will depend on the presence of a predisposing factor
      and may include metabolic control, androgen therapy withdrawn, or closure of the
      shunt when appropriate. Surgery is usually performed on large lesions. In the
      case of adenomatosis or multiple lesions, surgery will be adapted. Close followup
      is required in all cases.

PMID- 23555059
TI  - Effectiveness of Couple-Based HIV Counseling and Testing for Women Substance
      Users and Their Primary Male Partners: A Randomized Trial.
AB  - A randomized trial was conducted to test the effectiveness of couple-based HIV
      counseling and testing (CB-HIV-CT) and women-only relationship-focused HIV
      counseling and testing (WRF-HIV-CT) in reducing HIV risk compared to the National
      Institute on Drug Abuse HIV-CT standard intervention. Substance using HIV
      negative women and their primary heterosexual partner (N = 330 couples) were
      randomized to 1 of the 3 interventions. Follow-up assessments measuring HIV risk
      behaviors and other relevant variables were conducted at 3- and 9-months
      postintervention. Repeated measures generalized linear mixed model analysis was
      used to assess treatment effects. A significant reduction in HIV risk was
      observed over the 9-month assessment in the CB-HIV-CT group compared to that of
      the control group (b = -0.51, t[527] = -3.20, P = 0.002) and compared to that of
      the WRF-HIV-CT group (b = -0.34, t[527] = -2.07, P = 0.04), but no significant
      difference was observed between WRF-HIV-CT and controls (b = -0.17, t[527] = 
      1.09, P = 0.28). A brief couple-based HIV counseling and testing intervention
      designed to address both drug-related and sexual risk behaviors among substance
      using women and their primary male partners was shown to be more effective at
      reducing overall HIV risk compared to a standard HIV-CT intervention in an urban
      setting.

PMID- 23555060
TI  - Immunotherapy with Tolerogenic Dendritic Cells Alone or in Combination with
      Rapamycin Does Not Reverse Diabetes in NOD Mice.
AB  - Type 1 diabetes is a metabolic disease caused by autoimmunity towards beta 
      cells. Different strategies have been developed to restore beta -cell function
      and to reestablish immune tolerance to prevent and cure the disease. Currently,
      there is no effective treatment strategy to restore endogenous insulin secretion
      in patients with type 1 diabetes. This study aims to restore insulin secretion in
      diabetic mice with experimental antigen-specific immunotherapy alone or in
      combination with rapamycin, a compound well known for its immunomodulatory
      effect. Nonobese diabetic (NOD) mice develop spontaneous type 1 diabetes after 12
      weeks of age. Autologous tolerogenic dendritic cells-consisting in dendritic
      cells pulsed with islet apoptotic cells-were administered to diabetic NOD mice
      alone or in combination with rapamycin. The ability of this therapy to revert
      type 1 diabetes was determined by assessing the insulitis score and by measuring
      both blood glucose levels and C-peptide concentration. Our findings indicate that
      tolerogenic dendritic cells alone or in combination with rapamycin do not
      ameliorate diabetes in NOD mice. These results suggest that alternative
      strategies may be considered for the cure of type 1 diabetes.

PMID- 23555061
TI  - Liquid-supported dentures: a soft option-a case report.
AB  - Liquid-supported denture technique allows continued adaptation of denture to the
      mucosa both at resting and functional state. A complete denture prosthesis is
      unacceptable if it violates the foundation on which it rests. In this case, a
      technique for fabrication of a complete denture prosthesis that eliminates the
      disadvantages of tissue conditioners and soft liners (i.e., poor bond strength to
      acrylic, candidal colonization, etc.) and preserves the remaining tissues is
      described. Liquid-supported denture can be a permanent solution to some patients
      with problematic conditions like diabetes, xerostomia, atrophied ridge, and so
      forth.

PMID- 23555062
TI  - Exophthalmos: A Forgotten Clinical Sign of Cushing's Syndrome.
AB  - Exophthalmos is typically associated with Graves' ophthalmopathy. Although
      originally described by Harvey Cushing, exophthalmos is an underappreciated sign
      of Cushing's syndrome. We present a case of a 38-year-old female who presented
      with severe bilateral proptosis and was subsequently diagnosed with Cushings
      disease. We discuss the possible mechanisms causing exophthalmos in patients with
      either endogenous or exogenous hypercortisolemia.

PMID- 23555063
TI  - Pinworm infestation mimicking crohns' disease.
AB  - We here report a case of a young man who presented to his general practitioner
      with diarrhea. Inflammatory bowel disease was suspected and a colonoscopy showed
      aphthous lesions suggestive of Crohns' disease but biopsies revealed eggs of
      Enterobius vermicularis. When treated for this parasite, his symptoms were
      alleviated and a followup colonoscopy revealed a normal colon and distal ileum.
      Enterobius vermicularis is the most common parasite worldwide and has been
      attributed with many different presentations and pathologies. It is therefore
      necessary to maintain vigilance, even in high-income countries, in order to
      diagnose patients with one of the many atypical presentations of pinworms.

PMID- 23555064
TI  - Bilateral Multifocal Central Serous-Like Chorioretinopathy due to MEK Inhibition
      for Metastatic Cutaneous Melanoma.
AB  - Newer chemotherapeutic agents target extracellular signaling, including the
      mitogen-activated protein kinase kinase (MEK) pathway. We present a case of a 54
      year-old female who developed bilateral multifocal central serous-like
      chorioretinopathy shortly after starting MEK inhibition for metastatic cutaneous
      melanoma. There was a complete resolution of findings after drug stoppage. After
      resuming a lower dose of the MEK inhibitor, the findings recurred again but
      resolved after drug stoppage. Other etiologies were unlikely given the clinical
      course. The presumed mechanism involves toxicity to the retinal pigment
      epithelium, with breakdown of the blood-retinal barrier. Recognition of this side
      effect is important with this new class of chemotherapy.

PMID- 23555065
TI  - Early magnetic resonance detection of natalizumab-related progressive multifocal
      leukoencephalopathy in a patient with multiple sclerosis.
AB  - Diagnosis of progressive multifocal leukoencephalopathy is usually based on the
      clinical presentation, on the demonstration of the brain lesions at the magnetic
      resonance imaging examination, and on the detection of the JC virus DNA in the
      cerebrospinal fluid with high sensitive polymerase chain reaction. The role of
      magnetic resonance imaging specifically in natalizumab-associated progressive
      multifocal leukoencephalopathy is strengthening, and it is gaining importance not
      only as an irreplaceable diagnostic tool but also as a surveillance and risk
      stratifying tool in treated patients. While other imaging techniques such as
      computed tomography lack sensitivity and specificity, magnetic resonance
      performed with morphological and functional sequences offers clinicians the
      possibility to early identify the stage of the disease and the emergence of an
      immune reconstitution inflammatory syndrome after natalizumab blood removal
      plasmapheresis.

PMID- 23555066
TI  - Multicentric reticulohistiocytosis presenting with papulonodular skin lesions and
      arthritis mutilans.
AB  - Multicentric reticulohistiocytosis is a rare multisystem disorder of unknown
      etiology that is characterized by erosive polyarthritis and papulonodular lesions
      on the skin, mucous membranes, and internal organs. We report the case of a 54
      year-old female who was misdiagnosed as having rheumatoid arthritis and underwent
      numerous joint replacement surgeries for progressively destructive arthritis in
      her hands, shoulders, hips, and knees. The patient finally received a diagnosis
      of multicentric reticulohistiocytosis after histopathological examination of the
      patient's left knee arthroplasty which revealed a diffuse histiocytic infiltrate,
      multinucleated giant cells, and finely granulated eosinophilic cytoplasm with a
      ground-glass appearance.

PMID- 23555067
TI  - Mitral Valve Regurgitation: A Severe Complication following Left Ventricular
      Biopsy 15 Years after Heart Transplantation.
AB  - A 71-year-old male patient underwent orthotopic heart transplantation in 1995.
      Due to left heart catheterization 15 years later, biopsy from the left
      ventricular apex was performed for rejection screening. Two days later,
      echocardiography revealed severe mitral valve regurgitation requiring mitral
      valve replacement. This is a very rare case showing that left heart biopsy may
      lead to severe hemodynamic complications with the need for surgical intervention.

PMID- 23555068
TI  - Cardiovascular Inflammation 2012: Reactive Oxygen Species, SUMOylation, and
      Biomarkers in Cardiovascular Inflammation.

PMID- 23555069
TI  - New insights into mechanisms of cardioprotection mediated by thyroid hormones.
AB  - Heart failure represents the final common outcome in cardiovascular diseases.
      Despite significant therapeutic advances, morbidity and mortality of heart
      failure remain unacceptably high. Heart failure is preceded and sustained by a
      process of structural remodeling of the entire cardiac tissue architecture.
      Prevention or limitation of cardiac remodeling in the early stages of the process
      is a crucial step in order to ameliorate patient prognosis. Acquisition of novel
      pathophysiological mechanisms of cardiac remodeling is therefore required to
      develop more efficacious therapeutic strategies. Among all neuroendocrine
      systems, thyroid hormone seems to play a major homeostatic role in cardiovascular
      system. In these years, accumulating evidence shows that the "low
      triiodothyronine" syndrome is a strong prognostic, independent predictor of death
      in patients affected by both acute and chronic heart disease. In experimental
      models of cardiac hypertrophy or myocardial infarction, alterations in the
      thyroid hormone signaling, concerning cardiac mitochondrion, cardiac
      interstitium, and vasculature, have been suggested to be related to heart
      dysfunction. The aim of this brief paper is to highlight new developments in
      understanding the cardioprotective role of thyroid hormone in reverting
      regulatory networks involved in adverse cardiac remodeling. Furthermore, new
      recent advances on the role of specific miRNAs in thyroid hormone regulation at
      mitochondrion and interstitial level are also discussed.

PMID- 23555070
TI  - Depression increases stroke hospitalization cost: an analysis of 17,010 stroke
      patients in 2008 by race and gender.
AB  - Objective. This analysis focuses on the effect of depression on the cost of
      hospitalization of stroke patients. Methods. Data on 17,010 stroke patients
      (primary diagnosis) were extracted from 2008 Tennessee Hospital Discharge Data
      System. Three groups of patients were compared: (1) stroke only (S(O), n =
      7,850), (2) stroke + depression (S(+D), n = 3,965), and (3) stroke + other mental
      health diagnoses (S(+M), n = 5,195). Results. Of all adult patients, 4.3% were
      diagnosed with stroke. Stroke was more prevalent among blacks than whites (4.5%
      versus 4.2%, P < 0.001) and among males than females (5.1% versus 3.7%, P <
      0.001). Nearly one-quarter of stroke patients (23.3%) were diagnosed with
      depression/anxiety. Hospital stroke cost was higher among depressed stroke
      patients (S(+D)) compared to stroke only (S(O)) patients ($77,864 versus $47,790,
      P < 0.001), and among S(+D), cost was higher for black males compared to white
      depressed males ($97,196 versus $88,115, P < 0.001). Similar racial trends in
      cost emerged among S(+D) females. Conclusion. Depression in stroke patients is
      associated with increased hospitalization costs. Higher stroke cost among blacks
      may reflect the impact of comorbidities and the delay in care of serious health
      conditions. Attention to early detection of depression in stroke patients might
      reduce inpatient healthcare costs.

PMID- 23555071
TI  - Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro
      Culture of Respiratory Nasal Epithelium.
AB  - The nasal septa of fetal rabbits at 26 days of gestation were harvested by
      cesarean section of the does while under anesthesia and then exposed to
      Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4
      hours. A total of 240 explants were used. The tissues were examined using the
      Hematoxylin & Eosin technique. Then, semithin sections (0.5 MUm) were stained
      with toluidine blue and examined with indirect immunoperoxidase (IPI) and lectin
      histochemistry. The most frequent and statistically significant findings were as
      follows: (1) cell death and increased goblet cell activity when exposed to
      bacteria and (2) cell death, cytoplasmic vacuolation and infiltration of
      polymorphonuclear leukocytes when exposed to LPS. The lesions induced by the
      bacterium were more severe than with LPS alone, except for the cytoplasmic
      vacuolation in epithelial cells. IPI stained the ciliated border of the
      epithelium with the bacterium more intensely, while LPS lectin histochemistry
      preferentially labeled the cytoplasm of goblet cell. These data indicate that B.
      bronchiseptica and its LPS may have an affinity for specific glycoproteins that
      would act as adhesion receptors in both locations.

PMID- 23555072
TI  - Dietary Patterns and Wheezing in the Midst of Nutritional Transition: A Study in
      Brazil.
AB  - To assess the influence of dietary patterns on the prevalence of wheezing in the
      child and adolescent population in Northeastern Brazil. This is a cross-sectional
      study of male and female students, 6-12 years old, from the public elementary
      schools of Sao Francisco do Conde, Bahia, Northeastern Brazil. The report of
      wheezing in the past 12 months was collected using a questionnaire from the
      International Study of Asthma and Allergies in Childhood Program phase III,
      adapted to Portuguese. Consumption patterns were derived from principal component
      analysis based on the frequency of consumption of 97 food items by the food
      frequency questionnaire. We also obtained the anthropometric status, level of
      physical activity, pubertal development, and socioeconomic information, for each
      participant. Multivariate logistic regression analyses were used to assess the
      associations of interest. Of the children surveyed, 10.6% reported having
      wheezing. We identified 2 dietary patterns named Western and Prudent. We found a
      positive statistically significant association of the Western pattern with wheeze
      (odds ratio=1.77, 95% confidence interval: 1.10-2.84) after adjustment for total
      energy intake and controlling for potential confounders. The results showed that
      the Western dietary pattern was associated with wheezing. Our result is according
      with previous findings reported in several other studies.

PMID- 23555073
TI  - Development of a prognostic score using the complete blood cell count for
      survival prediction in unselected critically ill patients.
AB  - OBJECTIVE: The purpose of this study was to develop a new prognostic scoring
      system for critically ill patients using the simple complete blood cell count
      (CBC). METHODS: CBC measurements in samples from 306 patients in an intensive
      care unit were conducted with automated analyzers, including levels of
      neutrophils, lymphocytes, erythrocytes, hemoglobin, and platelets. The time of
      sampling and the time of death were recorded. Z values were calculated according
      to the measured values, reference mean values, and standard deviations. The
      prognostic score was equivalent to the median of the Z value of each of the
      measured parameters. RESULTS: There was a significant correlation between
      survival time and neutrophil, lymphocyte, and platelet levels (P < 0.05).
      Prognostic scores were calculated from the Z value of these three parameters.
      Survival times decreased as the prognostic score increased. CONCLUSIONS: This
      study suggests that a model that uses levels of neutrophils, lymphocytes, and
      platelets is potentially useful in the objective evaluation of survival time or
      disease severity in unselected critically ill patients.

PMID- 23555074
TI  - Antimicrobial photodynamic therapy for methicillin-resistant Staphylococcus
      aureus infection.
AB  - Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most
      common multidrug resistant bacteria both in hospitals and in the community. In
      the last two decades, there has been growing concern about the increasing
      resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection
      poses a serious problem for physicians and their patients. Photosensitizer
      mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and
      innovative approach for treating multidrug resistant infection. In spite of
      encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large
      in vitro studies, there are only few in vivo studies. Therefore, applying PDT in
      the clinic for MRSA infection is still a long way off.

PMID- 23555075
TI  - The use of continuous glucose monitoring combined with computer-based eMPC
      algorithm for tight glucose control in cardiosurgical ICU.
AB  - AIM: In postcardiac surgery patients, we assessed the performance of a system for
      intensive intravenous insulin therapy using continuous glucose monitoring (CGM)
      and enhanced model predictive control (eMPC) algorithm. METHODS: Glucose control
      in eMPC-CGM group (n = 12) was compared with a control (C) group (n = 12) treated
      by intravenous insulin infusion adjusted according to eMPC protocol with a
      variable sampling interval alone. In the eMPC-CGM group glucose measured with a
      REAL-Time CGM system (Guardian RT) served as input for the eMPC adjusting insulin
      infusion every 15 minutes. The accuracy of CGM was evaluated hourly using
      reference arterial glucose and Clarke error-grid analysis (C-EGA). Target glucose
      range was 4.4-6.1 mmol/L. RESULTS: Of the 277 paired CGM-reference glycemic
      values, 270 (97.5%) were in clinically acceptable zones of C-EGA and only 7
      (2.5%) were in unacceptable D zone. Glucose control in eMPC-CGM group was
      comparable to C group in all measured values (average glycemia, percentage of
      time above, within, and below target range,). No episode of hypoglycemia (<2.9
      mmol) occurred in eMPC-CGM group compared to 2 in C group. CONCLUSION: Our data
      show that the combination of eMPC algorithm with CGM is reliable and accurate
      enough to test this approach in a larger study population.

PMID- 23555078
TI  - Application of biotechnology in myocardial regeneration-tissue engineering triad:
      cells, scaffolds, and signaling molecules.

PMID- 23555077
TI  - PPAR activation induces M1 macrophage polarization via cPLA2-COX-2 inhibition,
      activating ROS production against Leishmania mexicana.
AB  - Defence against Leishmania depends upon Th1 inflammatory response and, a major
      problem in susceptible models, is the turnoff of the leishmanicidal activity of
      macrophages with IL-10, IL-4, and COX-2 upregulation, as well as
      immunosuppressive PGE2, all together inhibiting the respiratory burst. Peroxisome
      proliferator-activated receptors (PPAR) activation is responsible for macrophages
      polarization on Leishmania susceptible models where microbicide functions are
      deactivated. In this paper, we demonstrated that, at least for L. mexicana, PPAR
      activation, mainly PPAR gamma , induced macrophage activation through their
      polarization towards M1 profile with the increase of microbicide activity against
      intracellular pathogen L. mexicana. PPAR activation induced IL-10 downregulation,
      whereas the production of proinflammatory cytokines such as TNF- alpha , IL-1
      beta , and IL-6 remained high. Moreover, PPAR agonists treatment induced the
      deactivation of cPLA2-COX-2-prostaglandins pathway together with an increase in
      TLR4 expression, all of whose criteria meet the M1 macrophage profile. Finally,
      parasite burden, in treated macrophages, was lower than that in infected
      nontreated macrophages, most probably associated with the increase of respiratory
      burst in these treated cells. Based on the above data, we conclude that PPAR
      agonists used in this work induces M1 macrophages polarization via inhibition of
      cPLA2 and the increase of aggressive microbicidal activity via reactive oxygen
      species (ROS) production.

PMID- 23555079
TI  - Total 25-hydroxyvitamin D determination by an entry level triple quadrupole
      instrument: comparison between two commercial kits.
AB  - OBJECTIVE: 25-hydroxyvitamin D2/D3 (25-OHD2/D3) determination is a reliable
      biomarker for vitamin D status. Liquid chromatography-tandem mass spectrometry
      was recently proposed as a reference method for vitamin D status evaluation. The
      aim of this work is to compare two commercial kits (Chromsystems and PerkinElmer)
      for 25-OHD2/D3 determination by our entry level LC-MS/MS. DESIGN AND METHODS:
      Chromsystems kit adds an online trap column to an HPLC column and provides
      atmospheric pressure chemical ionization, isotopically labeled internal standard,
      and 4 calibrator points. PerkinElmer kit uses a solvent extraction and protein
      precipitation method. This kit can be used with or without derivatization with,
      respectively, electrospray and atmospheric pressure chemical ionization. For each
      analyte, there are isotopically labeled internal standards and 7 deuterated
      calibrator points. RESULTS: Performance characteristics are acceptable for both
      methods. Mean bias between methods calculated on 70 samples was 1.9 ng/mL. Linear
      regression analysis gave an R (2) of 0.94. 25-OHD2 is detectable only with
      PerkinElmer kit in derivatized assay option. CONCLUSION: Both methods are
      suitable for routine. Chromsystems kit minimizes manual sample preparation,
      requiring only protein precipitation, but, with our system, 25-OHD2 is not
      detectable. PerkinElmer kit without derivatization does not guarantee acceptable
      performance with our LC-MS/MS system, as sample is not purified online.
      Derivatization provides sufficient sensitivity for 25-OHD2 detection.

PMID- 23555076
TI  - Vasculogenic cytokines in wound healing.
AB  - Chronic wounds represent a growing healthcare burden that particularly afflicts
      aged, diabetic, vasculopathic, and obese patients. Studies have shown that
      nonhealing wounds are characterized by dysregulated cytokine networks that impair
      blood vessel formation. Two distinct forms of neovascularization have been
      described: vasculogenesis (driven by bone-marrow-derived circulating endothelial
      progenitor cells) and angiogenesis (local endothelial cell sprouting from
      existing vasculature). Researchers have traditionally focused on angiogenesis but
      defects in vasculogenesis are increasingly recognized to impact diseases
      including wound healing. A more comprehensive understanding of vasculogenic
      cytokine networks may facilitate the development of novel strategies to treat
      recalcitrant wounds. Further, the clinical success of endothelial progenitor cell
      based therapies will depend not only on the delivery of the cells themselves but
      also on the appropriate cytokine milieu to promote tissue regeneration. This
      paper will highlight major cytokines involved in vasculogenesis within the
      context of cutaneous wound healing.

PMID- 23555080
TI  - Validation of new allele-specific real-time PCR system for thiopurine
      methyltransferase genotyping in Korean population.
AB  - INTRODUCTION: Thiopurine drugs are metabolized via S-methylation and catalyzed by
      thiopurine S-methyltransferase (TPMT). Patients with very low TPMT activity are
      at high risk of fatal bone marrow toxicity when standard doses of thiopurine
      drugs are administered. TPMT genotyping can predict TPMT activity and is not
      affected by transfusion or red blood cell defects. Here, we report a new allele
      specific real-time polymerase chain reaction (PCR) system for thiopurine
      methyltransferase genotyping that is validated in Korean population. MATERIALS
      AND METHODS: Three major TPMT single-nucleotide polymorphisms (TPMT 2, 3B, and
      3C) were genotyped using real-time PCR with the allele-specific primers and
      probes. Internal positive controls were included in each well, and an automatic
      interpretative algorithm was applied. This system was validated using 244
      clinical samples and 2 commercial DNA samples that had been previously genotyped
      using PCR-direct sequencing. Results. All of the obtained results are concordant
      with those of the reference method. All of the internal positive control
      reactions were successful. The allele frequency of TPMT 3C was 2.05% (10 of 488
      alleles). All of the patients with variant alleles were heterozygotes, and no
      homozygotes were detected. No TPMT 2, 3A, or 3B alleles were observed in this
      Korean population. CONCLUSION: This rapid, accurate, and user-friendly genotyping
      system can be readily used to improve the efficacy and safety of thiopurine
      treatments in clinical practice.

PMID- 23555081
TI  - Phosphocitrate is potentially a disease-modifying drug for noncrystal-associated
      osteoarthritis.
AB  - Phosphocitrate (PC), a calcification inhibitor, inhibits the development of
      crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the
      molecular mechanisms underlying its disease-modifying effect remain elusive. This
      study sought to test the hypothesis that PC has calcium crystal-independent
      biological activities which are, at least in part, responsible for its disease
      modifying activity. We found that PC inhibited the proliferation of OA fibroblast
      like synoviocytes in the absence of calcium crystals. Consistent with its effect
      on cell proliferation, PC downregulated the expression of numerous genes
      classified in cell proliferation. PC also downregulated the expression of many
      genes classified in angiogenesis and inflammatory response including
      prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and
      chemokine (C-C motif) ligand 2. In contrast, PC upregulated the expression of
      many genes classified in musculoskeletal tissue development, including aggrecan,
      type I collagen, and insulin-like growth factor binding protein 5. These findings
      suggest that PC is not only a promising disease-modifying drug for crystal
      associated OA but also for noncrystal-associated OA.

PMID- 23555082
TI  - State-of-the-art fusion-finder algorithms sensitivity and specificity.
AB  - BACKGROUND: Gene fusions arising from chromosomal translocations have been
      implicated in cancer. RNA-seq has the potential to discover such rearrangements
      generating functional proteins (chimera/fusion). Recently, many methods for
      chimeras detection have been published. However, specificity and sensitivity of
      those tools were not extensively investigated in a comparative way. RESULTS: We
      tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder,
      MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect
      fusion events using synthetic and real datasets encompassing chimeras. The
      comparison analysis run only on synthetic data could generate misleading results
      since we found no counterpart on real dataset. Furthermore, most tools report a
      very high number of false positive chimeras. In particular, the most sensitive
      tool, ChimeraScan, reports a large number of false positives that we were able to
      significantly reduce by devising and applying two filters to remove fusions not
      supported by fusion junction-spanning reads or encompassing large intronic
      regions. CONCLUSIONS: The discordant results obtained using synthetic and real
      datasets suggest that synthetic datasets encompassing fusion events may not fully
      catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are
      still limited in sensitivity or specificity; thus, there is space for further
      improvement in the fusion-finder algorithms.

PMID- 23555083
TI  - Implementation of high resolution whole genome array CGH in the prenatal clinical
      setting: advantages, challenges, and review of the literature.
AB  - Array Comparative Genomic Hybridization analysis is replacing postnatal
      chromosomal analysis in cases of intellectual disabilities, and it has been
      postulated that it might also become the first-tier test in prenatal diagnosis.
      In this study, array CGH was applied in 64 prenatal samples with whole genome
      oligonucleotide arrays (BlueGnome, Ltd.) on DNA extracted from chorionic villi,
      amniotic fluid, foetal blood, and skin samples. Results were confirmed with
      Fluorescence In Situ Hybridization or Real-Time PCR. Fifty-three cases had normal
      karyotype and abnormal ultrasound findings, and seven samples had balanced
      rearrangements, five of which also had ultrasound findings. The value of array
      CGH in the characterization of previously known aberrations in five samples is
      also presented. Seventeen out of 64 samples carried copy number alterations
      giving a detection rate of 26.5%. Ten of these represent benign or variables of
      unknown significance, giving a diagnostic capacity of the method to be 10.9%. If
      karyotype is performed the additional diagnostic capacity of the method is 5.1%
      (3/59). This study indicates the ability of array CGH to identify chromosomal
      abnormalities which cannot be detected during routine prenatal cytogenetic
      analysis, therefore increasing the overall detection rate. In addition a thorough
      review of the literature is presented.

PMID- 23555084
TI  - The influence of Flightless I on Toll-like-receptor-mediated inflammation in a
      murine model of diabetic wound healing.
AB  - Impaired wound healing and ulceration represent a serious complication of both
      type 1 and type 2 diabetes. Cytoskeletal protein Flightless I (Flii) is an
      important inhibitor of wound repair, and reduced Flii gene expression in
      fibroblasts increased migration, proliferation, and adhesion. As such it has the
      ability to influence all phases of wound healing including inflammation,
      remodelling and angiogenesis. Flii has the potential to modulate inflammation
      through its interaction with MyD88 which it an adaptor protein for TLR4. To
      assess the effect of Flii on the inflammatory response of diabetic wounds, we
      used a murine model of streptozocin-induced diabetes and Flii genetic mice.
      Increased levels of Flii were detected in Flii transgenic murine wounds resulting
      in impaired healing which was exacerbated when diabetes was induced. When Flii
      levels were reduced in diabetic wounds of Flii-deficient mice, healing was
      improved and decreased levels of TLR4 were observed. In contrast, increasing the
      level of Flii in diabetic mouse wounds led to increased TLR4 and NF- kappa B
      production. Treatment of murine diabetic wounds with neutralising antibodies to
      Flii led to an improvement in healing with decreased expression of TLR4.
      Decreasing the level of Flii in diabetic wounds may therefore reduce the
      inflammatory response and improve healing.

PMID- 23555085
TI  - A review of haptoglobin typing methods for disease association study and
      preventing anaphylactic transfusion reaction.
AB  - Haptoglobin, the product of the Hp gene, is a glycoprotein involved in the
      scavenging of free hemoglobin. Haptoglobin levels increase or decrease in
      response to various acquired conditions, and they are also influenced by genetic
      predisposition. There were 2 major alleles, Hp (1) and Hp (2), and 1 minor
      allele, Hp (del) . Many researchers have attempted to study the haptoglobin types
      and their association with disease; however, no definitive conclusions have been
      reached yet. It is reported that patients who are genetically deficient in
      haptoglobin are at risk of anaphylaxis against blood components containing
      haptoglobin. Haptoglobin genotypes also affect the reference intervals of
      haptoglobin levels. Many studies have attempted to establish simple and accurate
      typing methods. In this paper, we have broadly reviewed several methods for
      haptoglobin typing-phenotyping, Southern blotting, conventional PCR, real-time
      PCR, and loop-mediated isothermal amplification. We discuss their
      characteristics, clinical applications, and limitations. The phenotyping methods
      are time consuming and labor intensive and not designed to detect patients
      harboring Hp (del) . The rapid and robust haptoglobin genotyping may help in
      preventing fatal anaphylactic reactions and in establishing the relationships
      between the haptoglobin phenotypes and diseases.

PMID- 23555086
TI  - Molecular and survival differences between familial and sporadic gastric cancers.
AB  - Mismatch repair (MMR) and germline E-cadherin (CDH1) mutations are two of the
      major pathways of carcinogenesis in familial gastric cancer (GC). A total of 260
      sporadic and 66 familial GC patients were enrolled and molecular and survival
      differences were compared. Familial GC patients had earlier onset and were
      diagnosed at an earlier stage and had both a better 5-year overall survival rate
      and 3-year disease-free survival rate compared with sporadic GC patients. Only in
      diffuse type GC, the MSI-H phenotype and abnormal MMR protein expression were
      significantly higher in familial GC than in sporadic GC. In MSI-H GC, MLH1
      promoter methylation was slightly higher in sporadic GC than familial GC (50%
      versus 23.1%), while the frequency of MMR gene mutation was slightly higher in
      familial GC than in sporadic GC (15.4% versus 3.1%). All of the patients with MMR
      gene mutation had diffuse type GC. Among familial GC patients with CDH1 mutation,
      most patients (72.3%) had diffuse type GC. In summary, for familial GC patients,
      we recommend screening of MSI status and CDH1 mutation especially for diffuse
      type GC. Because of the low incidence, mutation analysis of MMR gene might be
      considered in MSI-H familial GC with diffuse type only.

PMID- 23555087
TI  - Immunobiologic and antiinflammatory properties of a bark extract from
      Ampelozizyphus amazonicus Ducke.
AB  - Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The
      effect of an aqueous extract from this plant (SART) on the immune response was
      investigated by measuring immunoglobulin production induced by immunization with
      the antigen TNP-Ficoll in Plasmodium chabaudi-infected mice. SART treatment
      increased antigen-specific IgM and IgG levels in TNP-Ficoll-immunized mice. The B
      cell response during malarial infection was also modified by SART. There was an
      increase in total serum IgM and IgG and a decrease in the percentage of splenic
      plasma cells (CD138+ cells) in P. chabaudi-infected, SART-treated animals. SART
      (1, 3 or 10 mg/kg, p.o.) and the reference drug dexamethasone (5 mg/kg) were also
      tested in carrageenan-induced leukocyte migration to the subcutaneous air pouch
      (SAP). All SART doses significantly reduced leukocyte migration into the SAP. The
      protein concentration resulting from extravasation into the peritoneum was also
      significantly reduced. Our data indicate that SART possesses immunomodulatory
      properties, inducing an in vivo modification of the B lymphocyte response and
      anti-inflammatory properties, which are partly due to a reduction in cell
      migration and are most likely due to an inhibition of the production of
      inflammatory mediators. Preliminary HPLC-ESI-MS/MS analysis of SART shows a
      complex saponin profile with deprotonated molecule [M-H](-) ions in the range of
      m/z 800-1000.

PMID- 23555088
TI  - Lactobacillus plantarum LG42 isolated from gajami sik-hae inhibits adipogenesis
      in 3T3-L1 adipocyte.
AB  - We investigated whether lactic acid bacteria isolated from gajami sik-hae (GLAB)
      are capable of reducing the intracellular lipid accumulation by downregulating
      the expression of adipogenesis-related genes in differentiated 3T3-L1 cells. The
      GLAB, Lactobacillus plantarum LG42, significantly decreased the intracellular
      triglyceride storage and the glycerol-3-phosphate dehydrogenase (GPDH) activity
      in a dose-dependent manner. mRNA expression of transcription factors like
      peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer
      binding protein (C/EBP) alpha involved in adipogenesis was markedly decreased by
      the GLAB treatment. Moreover, the GLAB also decreased the expression level of
      adipogenic markers like adipocyte fatty acid binding protein (aP2), leptin, GPDH,
      and fatty acid translocase (CD36) significantly. These results suggest that the
      GLAB inhibits lipid accumulation in the differentiated adipocyte through
      downregulating the expression of adipogenic transcription factors and other
      specific genes involved in lipid metabolism.

PMID- 23555089
TI  - Brazilian Cerrado soil Actinobacteria ecology.
AB  - A total of 2152 Actinobacteria strains were isolated from native Cerrado
      (Brazilian Savannah) soils located in Passos, Luminarias, and Arcos
      municipalities (Minas Gerais State, Brazil). The soils were characterised for
      chemical and microbiological analysis. The microbial analysis led to the
      identification of nine genera (Streptomyces, Arthrobacter, Rhodococcus,
      Amycolatopsis, Microbacterium, Frankia, Leifsonia, Nakamurella, and
      Kitasatospora) and 92 distinct species in both seasons studied (rainy and dry).
      The rainy season produced a high microbial population of all the aforementioned
      genera. The pH values of the soil samples from the Passos, Luminarias, and Arcos
      regions varied from 4.1 to 5.5. There were no significant differences in the
      concentrations of phosphorus, magnesium, and organic matter in the soils among
      the studied areas. Samples from the Arcos area contained large amounts of
      aluminium in the rainy season and both hydrogen and aluminium in the rainy and
      dry seasons. The Actinobacteria population seemed to be unaffected by the high
      levels of aluminium in the soil. Studies are being conducted to produce bioactive
      compounds from Actinobacteria fermentations on different substrates. The present
      data suggest that the number and diversity of Actinobacteria spp. in tropical
      soils represent a vast unexplored resource for the biotechnology of bioactives
      production.

PMID- 23555090
TI  - Identification and biotechnological application of novel regulatory genes
      involved in Streptomyces polyketide overproduction through reverse engineering
      strategy.
AB  - Polyketide belongs to a family of abundant natural products typically produced by
      the filamentous soil bacteria Streptomyces. Similar to the biosynthesis of most
      secondary metabolites produced in the Streptomyces species, polyketide compounds
      are synthesized through tight regulatory networks in the cell, and thus extremely
      low levels of polyketides are typically observed in wild-type strains. Although
      many Streptomyces polyketides and their derivatives have potential to be used as
      clinically important pharmaceutical drugs, traditional strain improvement
      strategies such as random recursive mutagenesis have long been practiced with
      little understanding of the molecular basis underlying enhanced polyketide
      production. Recently, identifying, understanding, and applying a novel polyketide
      regulatory system identified from various Omics approaches, has become an
      important tool for rational Streptomyces strain improvement. In this paper, DNA
      microarray-driven reverse engineering efforts for improving titers of polyketides
      are briefly summarized, primarily focusing on our recent results of
      identification and application of novel global regulatory genes such as wblA,
      SCO1712, and SCO5426 in Streptomyces species. Sequential targeted gene
      manipulation involved in polyketide biosynthetic reguation synergistically
      provided an efficient and rational strategy for Streptomyces strain improvement.
      Moreover, the engineered regulation-optimized Streptomyces mutant strain was
      further used as a surrogate host for heterologous expression of polyketide
      pathway.

PMID- 23555091
TI  - Biomarkers of hypochromia: the contemporary assessment of iron status and
      erythropoiesis.
AB  - Iron status is the result of the balance between the rate of erythropoiesis and
      the amount of the iron stores. Direct consequence of an imbalance between the
      erythroid marrow iron requirements and the actual supply is a reduction of red
      cell hemoglobin content, which causes hypochromic mature red cells and
      reticulocytes. The diagnosis of iron deficiency is particularly challenging in
      patients with acute or chronic inflammatory conditions because most of the
      biochemical markers for iron metabolism (serum ferritin and transferrin ) are
      affected by acute phase reaction. For these reasons, interest has been generated
      in the use of erythrocyte and reticulocyte parameters, available on the modern
      hematology analyzers. Reported during blood analysis routinely performed on the
      instrument, these parameters can assist in early detection of clinical conditions
      (iron deficiency, absolute, or functional; ineffective erythropoiesis, including
      iron restricted or thalassemia), without additional cost. Technological progress
      has meant that in recent years modern analyzers report new parameters that
      provide further information from the traditional count. Nevertheless these new
      parameters are exclusive of each manufacturer, and they are patented. This is an
      update of these new laboratory test biomarkers of hypochromia reported by
      different manufactures, their meaning, and clinical utility on daily practice.

PMID- 23555092
TI  - Expression of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase involved in
      chondroitin sulfate synthesis is responsible for pulmonary metastasis.
AB  - Chondroitin sulfate (CS) containing E-disaccharide units, glucuronic acid-N
      acetylgalactosamine(4, 6-O-disulfate), at surfaces of tumor cells plays a key
      role in tumor metastasis. However, the molecular mechanism of the metastasis
      involving the CS chain-containing E-units is not fully understood. In this study,
      to clarify the role of E-units in the metastasis and to search for potential
      molecular targets for anticancer drugs, the isolation and characterization of
      Lewis lung carcinoma (LLC) cells stably downregulated by the knockdown for the
      gene encoding N-acetylgalactosamine 4-O-sulfate 6-O-sulfotransferase (GalNAc4S
      6ST), which is responsible for the formation of E-units in CS chains, were
      performed. Knockdown of GalNAc4S-6ST in LLC cells resulted in a reduction in the
      proportion of E-units, in adhesiveness to extracellular matrix adhesion molecules
      and in proliferation in vitro. Furthermore, the stable downregulation of GalNAc4S
      6ST expression in LLC cells markedly inhibited the colonization of the lungs by
      inoculated LLC cells and invasive capacity of LLC cells. These results provide
      clear evidence that CS chain-containing E-units and/or GalNAc4S-6ST play a
      crucial role in pulmonary metastasis at least through the increased adhesion and
      the invasive capacity of LLC cells and also provides insights into future drug
      targets for anticancer treatment.

PMID- 23555093
TI  - Construction, expression, and characterization of thymosin alpha 1 tandem repeats
      in Escherichia coli.
AB  - Thymosin alpha 1 (T alpha 1), which is composed of 28 amino acids, has been
      commercialized worldwide for its immune-modulatory and antitumor effects. T alpha
      1 can stimulate T cell proliferation and differentiation from bone marrow stem
      cells, augment cell-mediated immune responses, and regulate homeostasis of immune
      system. In this study, we developed a novel strategy to produce T alpha 1
      concatemer (T alpha 13) in Escherichia coli and compared its activity with
      chemically synthesized T alpha 1. Results showed that T alpha 13 can more
      effectively stimulate T cell proliferation and significantly upregulate IL-2
      receptor expression. We concluded that the expression system for T alpha 1
      concatemer was constructed successfully, which could serve as an efficient tool
      for the production of large quantities of the active protein.

PMID- 23555094
TI  - Environmental lead exposure accelerates progressive diabetic nephropathy in type
      II diabetic patients.
AB  - Whether environmental lead exposure has a long-term effect on progressive
      diabetic nephropathy in type II diabetic patients remains unclear. A total of 107
      type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular
      filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead
      burden (BLB) (<600  MU g/72 hr in EDTA mobilization tests) and no history of
      exposure to lead were prospectively followed for 2 years. Patients were divided
      into high-normal BLB (>80  MU g) and low-normal BLB (<80  MU g) groups. The
      primary outcome was a 2-fold increase in the initial creatinine levels, long-term
      dialysis, or death. The secondary outcome was a change in eGFR over time. Forty
      five patients reached the primary outcome within 2 years. Although there were no
      differences in baseline data and renal function, progressive nephropathy was
      slower in the low-normal BLB group than that in the high-normal BLB group. During
      the study period, we demonstrated that each 100  MU g increment in BLB and each
      10  MU g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72
      m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by
      generalized equations. Moreover, BLB was associated with increased risk of
      achieving primary outcome. Environmental exposure to lead may have a long-term
      effect on progressive diabetic nephropathy in type II diabetic patients.

PMID- 23555095
TI  - Potential use of Atlantic cod trypsin in biomedicine.
AB  - Surface proteins of viruses and bacteria used for cell attachment and invasion
      are candidates for degradation by proteases. Trypsin from Atlantic cod (Gadus
      morhua) was previously demonstrated to have efficacy against influenza viruses in
      vitro and on skin. In this paper, cod trypsin is shown to be 3-12 times more
      effective in degrading large native proteins than its mesophilic analogue, bovine
      trypsin. This is in agreement with previous findings where cod trypsin was found
      to be the most active among twelve different proteases in cleaving various
      cytokines and pathological proteins. Furthermore, our results show that cod
      trypsin has high efficacy against herpes simplex virus type 1 (HSV-1) and the
      respiratory syncytial virus (RSV) in vitro. The results on the antipathogenic
      properties of cod trypsin are important because rhinovirus, RSV, and influenza
      are the most predominant pathogenic viruses in upper respiratory tract
      infections. Results from a clinical study presented in this paper show that a
      specific formulation containing cod trypsin was preferred for wound healing over
      other methods used in the study. Apparently, the high digestive ability of the
      cold-adapted cod trypsin towards large native proteins plays a role in its
      efficacy against pathogens and its positive effects on wounds.

PMID- 23555096
TI  - Detection of intracellular Factor VIII protein in peripheral blood mononuclear
      cells by flow cytometry.
AB  - Flow cytometry is widely used in cancer research for diagnosis, detection of
      minimal residual disease, as well as immune monitoring and profiling following
      immunotherapy. Detection of specific host proteins for diagnosis predominantly
      uses quantitative PCR and western blotting assays. In this study, we optimized a
      flow cytometry-based detection assay for Factor VIII protein in peripheral blood
      mononuclear cells (PBMCs). An indirect intracellular staining (ICS) method was
      standardized using monoclonal antibodies to different domains of human Factor
      VIII protein. The FVIII protein expression level was estimated by calculating the
      mean and median fluorescence intensities (MFI) values for each monoclonal
      antibody. ICS staining of transiently transfected cell lines supported the
      method's specificity. Intracellular FVIII protein expression was also detected by
      the monoclonal antibodies used in the study in PBMCs of five blood donors. In
      summary, our data suggest that intracellular FVIII detection in PBMCs of
      hemophilia A patients can be a rapid and reliable method to detect intracellular
      FVIII levels.

PMID- 23555097
TI  - MLST genotypes and antibiotic resistance of Campylobacter spp. isolated from
      poultry in Grenada.
AB  - This study determined whether multilocus sequence types (MLST) of Campylobacter
      from poultry in 2 farms in Grenada, West Indies, differed by farm, antimicrobial
      resistance and farm antibiotic use. Farm A used fluoroquinolones in the water and
      Farm B used tetracyclines. The E-test was used to determine resistance of
      isolates to seven antibiotics. PCR of the IpxA gene confirmed species and MLST
      was used to characterize 38 isolates. All isolates were either C. jejuni or C.
      coli. Farm antibiotic use directly correlated with antimicrobial resistance of
      Campylobacter isolates. Almost 80% of the isolates from Farm A were
      fluoroquinolone resistant and 17.9% of the isolates from Farm B were
      fluoroquinolone resistant. All Campylobacter isolates from Farm A were
      tetracycline sensitive, whereas 35.7% of isolates from Farm B were tetracycline
      resistant. Six previously recognized sequence types (STs) and 2 novel STs were
      identified. Previously recognized STs were those overwhelmingly reported from
      poultry and humans globally. Isolates with the same ST did not always have the
      same antibiotic resistance profile. There was little ST overlap between the farms
      suggesting that within-farm transmission of Campylobacter genotypes may dominate.
      MLST typing was useful for tracking Campylobacter spp. among poultry units and
      can help elucidate Campylobacter host-species population structure and its
      relevance to human health.

PMID- 23555098
TI  - Three new steroidal glycosides from the roots of Cynanchum stauntonii.
AB  - Three new steroidal glycosides, named as stauntosides L, M, and N (1-3), along
      with one known C21 steroidal glycoside, anhydrohirundigenin monothevetoside (4),
      were isolated from the 95% ethanol extract of the roots of Cynanchum stauntonii.
      The structures of these new compounds were elucidated on the basis of extensive
      spectroscopic analyses, mainly 1D and 2D NMR, HRESI-MS, and chemical methods.

PMID- 23555099
TI  - Coagulation proteins influencing global coagulation assays in cirrhosis:
      hypercoagulability in cirrhosis assessed by thrombomodulin-induced thrombin
      generation assay.
AB  - BACKGROUND: Liver disease is accompanied by profound hemostatic disturbances. We
      investigated the influences of pro- and anticoagulation factors on global
      coagulation tests including prothrombin time (PT), activated partial
      thromboplastin time (aPTT), and thrombin generation assay (TGA) in cirrhosis. We
      also investigated whether cirrhotic patients exhibit hypo- or hypercoagulability
      using the TGA. METHODS: The TGA was performed on a calibrated automated
      thrombogram, given lag time, endogenous thrombin potential (ETP), and peak
      thrombin in 156 cirrhotic patients and 73 controls. RESULTS: PT was determined
      according to the factor (F) II, FV, FVII, FIX, and protein C levels. We observed
      that aPTT was dependent on FII, FIX, and FX levels. The ETP was dependent on FII,
      antithrombin, and protein C with 5 pM tissue factor (TF) stimulation, and FIX and
      protein C at 1 pM TF. The ETP ratio with 1 pM TF increased significantly in
      cirrhosis, indicating hypercoagulability, whereas that with 5 pM TF did not
      increase in cirrhosis. CONCLUSION: PT and the TGA are sensitive to protein C
      levels. Even with prolonged PT, the TGA can detect hypercoagulability in
      cirrhosis. Further studies should evaluate global coagulation status in cirrhosis
      patients using the newly devised TGA system.

PMID- 23555100
TI  - Expression of pluripotency and oocyte-related genes in single putative stem cells
      from human adult ovarian surface epithelium cultured in vitro in the presence of
      follicular fluid.
AB  - The aim of this study was to trigger the expression of genes related to oocytes
      in putative ovarian stem cells scraped from the ovarian surface epithelium of
      women with premature ovarian failure and cultured in vitro in the presence of
      follicular fluid, rich in substances for oocyte growth and maturation. Ovarian
      surface epithelium was scraped and cell cultures were set up by scrapings in five
      women with nonfunctional ovaries and with no naturally present mature follicles
      or oocytes. In the presence of donated follicular fluid putative stem cells grew
      and developed into primitive oocyte-like cells. A detailed single-cell gene
      expression profiling was performed to elucidate their genetic status in
      comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The
      ovarian cell cultures depleted/converted reproductive hormones from the culture
      medium. Estradiol alone or together with other substances may be involved in
      development of these primitive oocyte-like cells. The majority of primitive
      oocyte-like cells was mononuclear and expressed several genes related to
      pluripotency and oocytes, including genes related to meiosis, although they did
      not express some important oocyte-specific genes. Our work reveals the presence
      of putative stem cells in the ovarian surface epithelium of women with premature
      ovarian failure.

PMID- 23555101
TI  - Role of melanin in melanocyte dysregulation of reactive oxygen species.
AB  - We have recently reported a potential alternative tumor suppressor function for
      p16 relating to its capacity to regulate oxidative stress and observed that
      oxidative dysregulation in p16-depleted cells was most profound in melanocytes,
      compared to keratinocytes or fibroblasts. Moreover, in the absence of p16
      depletion or exogenous oxidative insult, melanocytes exhibited significantly
      higher basal levels of reactive oxygen species (ROS) than these other epidermal
      cell types. Given the role of oxidative stress in melanoma development, we
      speculated that this increased susceptibility of melanocytes to oxidative stress
      (and greater reliance on p16 for suppression of ROS) may explain why genetic
      compromise of p16 is more commonly associated with predisposition to melanoma
      rather than other cancers. Here we show that the presence of melanin accounts for
      this differential oxidative stress in normal and p16-depleted melanocytes. Thus
      the presence of melanin in the skin appears to be a double-edged sword: it
      protects melanocytes as well as neighboring keratinocytes in the skin through its
      capacity to absorb UV radiation, but its synthesis in melanocytes results in
      higher levels of intracellular ROS that may increase melanoma susceptibility.

PMID- 23555102
TI  - Detection of Mycobacterium tuberculosis by using loop-mediated isothermal
      amplification combined with a lateral flow dipstick in clinical samples.
AB  - Tuberculosis (TB) is a communicable disease caused by the bacterium Mycobacterium
      tuberculosis (MTB) and is a persistent problem in the developing countries. Loop
      mediated isothermal amplification (LAMP) allows DNA to be amplified rapidly at a
      constant temperature. Here, a LAMP method was combined with a chromatographic
      lateral-flow dipstick (LFD) to detect IS6110 gene of M. tuberculosis specifically
      and rapidly. The reaction was optimized at 63 degrees C for 60 min, and the
      amplified DNA hybridized to an FITC-labeled oligonucleotide probe for 5 min was
      detected at the LFD test line 5 min after application. Excluding the step of DNA
      extraction, the test results could be generated approximately within 1 h. In
      addition to the advantage of short assay time, this technique could avoid the
      contact of carcinogenic ethidium bromide due to the exclusion of the
      electrophoresis analysis step. Furthermore, the data indicated that LAMP-LFD
      could detect M. tuberculosis genomic DNA as little as 5 pg. The technique showed
      a significant specificity since no cross-hybridization to M. intracellulare
      (MIC), M. fortuitum (MFT), M. avium (MAV), M. kansasii (MKS), and M. gordonae
      (MGD) genomic DNAs was observed. In the clinical unknown samples test, the
      sensitivity of LAMP-LFD was 98.92   % and the specificity was 100   % compared to
      those of the standard culture assay. Based on its sensitivity, specificity,
      rapidity, low cost, and convenience, LAMP-LFD could be applicable for use in both
      laboratories and epidemiological surveys of MTB.

PMID- 23555104
TI  - Performance evaluation of Al-Zahra academic medical center based on Iran balanced
      scorecard model.
AB  - BACKGROUND: Growth and development in any country's national health system,
      without an efficient evaluation system, lacks the basic concepts and tools
      necessary for fulfilling the system's goals. The balanced scorecard (BSC) is a
      technique widely used to measure the performance of an organization. The basic
      core of the BSC is guided by the organization's vision and strategies, which are
      the bases for the formation of four perspectives of BSC. The goal of this
      research is the performance evaluation of Al-Zahra Academic Medical Center in
      Isfahan University of Medical Sciences, based on Iran BSC model. MATERIALS AND
      METHODS: This is a combination (quantitative-qualitative) research which was done
      at Al-Zahra Academic Medical Center in Isfahan University of Medical Sciences in
      2011. The research populations were hospital managers at different levels.
      Sampling method was purposive sampling in which the key informed personnel
      participated in determining the performance indicators of hospital as the BSC
      team members in focused discussion groups. After determining the conceptual
      elements in focused discussion groups, the performance objectives (targets) and
      indicators of hospital were determined and sorted in perspectives by the group
      discussion participants. Following that, the performance indicators were
      calculated by the experts according to the predetermined objectives; then, the
      score of each indicator and the mean score of each perspective were calculated.
      RESULTS: Research findings included development of the organizational mission,
      vision, values, objectives, and strategies. The strategies agreed upon by the
      participants in the focus discussion group included five strategies, which were
      customer satisfaction, continuous quality improvement, development of human
      resources, supporting innovation, expansion of services and improving the
      productivity. Research participants also agreed upon four perspectives for the Al
      Zahra hospital BSC. In the patients and community perspective (customer), two
      objectives and three indicators were agreed upon, with a mean score of 75.9%. In
      the internal process perspective, 4 objectives and 14 indicators were agreed
      upon, with a mean score of 79.37%. In the learning and growth perspective, four
      objectives and eight indicators were agreed upon, with a mean score of 81.11%.
      Finally, in the financial perspective, two objectives and five indicators were
      agreed upon, with a mean score of 67.15%. CONCLUSION: One way to create demand
      for hospital services is performance evaluation by paying close attention to all
      BSC perspectives, especially the non-financial perspectives such as customers and
      internal processes perspectives. In this study, the BSC showed the differences in
      performance level of the organization in different perspectives, which would
      assist the hospital managers improve their performance indicators. The learning
      and growth perspective obtained the highest score, and the financial perspective
      obtained the least score. Since the learning and growth perspective acts as a
      base for all other perspectives and they depend on it, hospitals must
      continuously improve the service processes and the quality of services by
      educating staff and updating their policies and procedures. This can increase
      customer satisfaction and productivity and finally improve the BSC in financial
      perspective.

PMID- 23555103
TI  - A case-control study between gene polymorphisms of polyunsaturated fatty acid
      metabolic rate-limiting enzymes and acute coronary syndrome in Chinese Han
      population.
AB  - The purpose of this study is to analyze the relationship between the
      polymorphisms of fatty acid desaturase 1 (FADS1), fatty acid desaturase 2
      (FADS2), and elongation of very long-chain fatty acids-like 2 (ELOVL2) and acute
      coronary syndrome (ACS) in Chinese Han population. Therefore, we selected three
      single nucleotide polymorphisms (SNPs) from these candidate genes and genotyped
      them using PCR-based restriction fragment length polymorphism analysis in 249 ACS
      patients and 240 non-ACS subjects, as were Han Chinese ancestry. The results
      showed that rs174556 in the FADS1 gene is found to be in allelic association (P =
      0.003 ) and genotypic association (P = 0.036) with ACS. The frequencies of
      rs174556 minor allele (T) in case group were obviously higher than in control
      group. The trans-phase gene-gene interaction analysis showed that the combined
      genotype of rs174556 (T/T) and rs3756963 (T/T) was associated with ACS (P =
      0.031). And the results suggest that, for rs174556 C>T, the CT/TT genotypes were
      more likely to lead in ACS in subjects with hypertension after correction of all
      risk factors (OR = 4.236, 95% CI, 2.216-7.126). These findings suggest that the
      polymorphisms of rs174556 in the FADS1 gene are very likely to be associated with
      ACS in Chinese Han population, especially in subjects with hypertension.

PMID- 23555105
TI  - Cognitive-behavioral therapy and quality of life: An experience among cardiac
      patients.
AB  - BACKGROUND: Considering the significance of quality of life in chronic diseases
      and the role of education in its improvement, this study was performed to
      investigate the effect of cognitive-behavioral therapy on improving the quality
      of life of cardiovascular patients in Isfahan city. MATERIALS AND METHODS: In
      this experimental study, 56 patients, who referred to Chamran Hospital and
      Isfahan Cardiovascular Research Center, were randomly selected and assigned to
      two groups, i.e. experiment and control. The experiment group was trained in
      eight sessions, each session taking 2 hours. Both groups received MacNew quality
      of life questionnaire before and 2 weeks after treatment. Some demographic data
      were also gathered along with the questionnaire. Data were analyzed by SPSS
      software using statistical tests such as independent t-test, Chi-square, and
      analysis of covariance. RESULTS: Observing the possible effect of pre-test,
      cognitive-behavioral therapy had a significant effect on the total score of
      quality of life and its three subscales. CONCLUSION: It seems that along with
      other medical therapies, making use of cognitive-behavioral intervention is an
      appropriate method for improving the quality of life of cardiovascular patients.

PMID- 23555106
TI  - Medical education and information and communication technology.
AB  - BACKGROUND: Information and communication technology (ICT) has brought many
      changes in medical education and practice in the last couple of decades. Teaching
      and learning medicine particularly has gone under profound changes due to
      computer technologies, and medical schools around the world have invested heavily
      either in new computer technologies or in the process of adapting to this
      technological revolution. In order to catch up with the rest of the world,
      developing countries need to research their options in adapting to new computer
      technologies. MATERIALS AND METHODS: This descriptive survey study was designed
      to assess medical students' computer and Internet skills and their attitude
      toward ICT. RESULTS: Research findings showed that the mean score of self
      perceived computer knowledge for male students in general was greater than for
      female students. Also, students who had participated in various prior computer
      workshops, had access to computer, Internet, and e-mail, and frequently checked
      their e-mail had higher mean of self-perceived knowledge and skill score.
      Finally, students with positive attitude toward ICT scored their computer
      knowledge higher than those who had no opinion. CONCLUSIONS: The results have
      confirmed that the medical schools, particularly in developing countries, need to
      bring fundamental changes such as curriculum modification in order to integrate
      ICT into medical education, creating essential infrastructure for ICT use in
      medical education and practice, and structured computer training for faculty and
      students.

PMID- 23555107
TI  - Motivation and academic achievement in medical students.
AB  - BACKGROUND: Despite their ascribed intellectual ability and achieved academic
      pursuits, medical students' academic achievement is influenced by motivation.
      This study is an endeavor to examine the role of motivation in the academic
      achievement of medical students. MATERIALS AND METHODS: In this cross-sectional
      correlational study, out of the total 422 medical students, from 4th to final
      year during the academic year 2007-2008, at School of Medicine, Isfahan
      University of Medical Sciences, 344 participated in completion of the Inventory
      of School Motivation (ISM), comprising 43 items and measuring eight aspects of
      motivation. The gold standard for academic achievement was their average academic
      marks at pre-clinical and clinical levels. Data were computer analyzed by running
      a couple of descriptive and analytical tests including Pearson Correlation and
      Student's t-student. RESULTS: Higher motivation scores in areas of competition,
      effort, social concern, and task were accompanied by higher average marks at pre
      clinical as well as clinical levels. However, the latter ones showed greater
      motivation for social power as compared to the former group. Task and competition
      motivation for boys was higher than for girls. CONCLUSION: In view of our
      observations, students' academic achievement requires coordination and
      interaction between different aspects of motivation.

PMID- 23555108
TI  - A study of family health problems in Iran from the stakeholders' perspective.
AB  - BACKGROUND: Family health is one of the World Health Organization's (WHO)
      programs concerning individuals' and families' health and development. If
      properly implemented, family health may ensure the health of human beings and
      support their self-fulfillment; and may pave the way for bringing up a healthier
      and better generation by achieving two important and specific quantitative and
      qualitative results. This study aims at establishing the existing problems in the
      medical education system with respect to family health, which may be managed by
      the family health professional if a Masters' course educational program is
      developed. MATERIALS AND METHODS: In this cross-sectional, descriptive study,
      five Type-1 and four Type-2 and Type-3 universities were randomly selected. Then,
      the faculty members of health services/public health departments, health
      managers, health and treatment networks managers, personnel of provincial health
      centers in family health units, and also public health B. S. students were
      surveyed on the existing problems in the national health system which can be
      solved by family health professional. A questionnaire containing one open-ended
      and several demographic questions was sent by mail for some and personally handed
      over to some others. Since the data were of a qualitative nature, first the
      categories were specified through content analysis and then the opinions of each
      category of individuals were differentiated based on the relevant categories.
      RESULTS: Results obtained from the comments of the study population led to
      specification of problems in health system, which could be solved by the family
      health senior expert. Such problems were categorized into six groups as: Planning
      and implementation, research, education, management, service-providing, and
      cultural problems. CONCLUSION: Given the problems in our nation concerning
      various family health issues, the field of family health in the levels of
      associate and bachelor degrees cannot respond to all public requirements, and
      health personnel in these levels do not possess various professional, planning,
      research, and educational skills required to analyze family health problems.
      Therefore, it is suggested that a Masters' course educational program be
      developed.

PMID- 23555109
TI  - Information and communications technology, culture, and medical universities;
      organizational culture and netiquette among academic staff.
AB  - INTRODUCTION: Netiquette is appropriate behavioral etiquette when communicating
      through computer networks or virtual space. Identification of a dominant
      organizational culture and its relationship with a network culture offers applied
      guidelines to top managers of the university to expand communications and develop
      and learn organization through the use of the internet. The aim of this research
      was to examine the relationship between netiquette and organizational culture
      among faculty members of the Isfahan University of Medical Sciences (IUMS), Iran.
      MATERIALS AND METHODS: To achieve this aim, the research method in this study was
      correlational research, which belonged to the category of descriptive survey
      research. The target population comprised of 594 faculty members of the IUMS,
      from which a sample of 150 was randomly selected, based on a simple stratified
      sampling method. For collecting the required data, two researcher-made
      questionnaires were formulated. Even as the first questionnaire tended to measure
      the selected sample members' organizational culture according to Rabbin's model
      (1999), the latter was designed in the Health Management and Economic Research
      Center (HMERC), to evaluate netiquette. The reliability of the questionnaires was
      computed by Choronbach's alpha coefficient formula and they happened to be 0.97
      and 0.89, respectively. Ultimately, SPSS Version #15 was used for the statistical
      analysis of the data. RESULTS: The findings revealed that the organizational
      culture and netiquette were below average level among the sample members,
      signifying a considerable gap in the mean. In spite of that, there was no
      significant relationship between netiquette and the organizational culture of the
      faculty members. CONCLUSION: Emphasizing the importance of cultural preparation
      and a network user's training, this research suggests that the expansion of
      network culture rules among IUMS and organizational official communications,
      through the use of internet networks, in order to promote university netiquette
      and convenience in communication development, on the basis of special etiquette.

PMID- 23555110
TI  - Developing a clinical performance logbook for nursing students receiving cardiac
      care field training.
AB  - BACKGROUND: Assessment is one of the teachers' most important activities in
      teaching process which bears many purposes. With the rapid change of different
      sciences,old methods and tools are not meeting the present needs. Since in
      medical sciences, half of the educational course, including nursing
      courses,occurs at patients' bedside, the assessment of clinical competency is of
      great importance. In this study the goals , skills and expected level of
      competency for each skill and procedural skills needed for training nursing
      studentsreceivingcardiac care field training compiled. MATERIALS AND METHODS:
      This research was a descriptive measurement study conducted in Esfahan in 2010
      2011. Research community was nursing trainers who are responsible for training
      students takingcardiac care field training coursesin state medical science
      universities all over the country. Sampling was performed first in the form of
      the multi-stage cluster and then after selecting the colleges, their trainers
      entered the study in the form of census. To gather the information, after
      literature review and performing a focusing group, an initial questionnaire was
      compiled and survey was conducted using Delphi three-stage method. RESULTS: After
      literature review and focus group, 23 modules and 142 skills in the first section
      and 14 general procedural skills and 15 special procedural skills in the second
      stage were compiled. Finally after passing the Delphi stages, 150 skills in the
      form of 23 modules in the first section and 14 general procedural skill and 13
      special procedural skills were obtainedin the second section. The expectancy
      levels of all the skills were also determined. CONCLUSION: This study has
      introduced an assessment pattern in the form of clinical performance logbook
      which can be a valuable tool for assessing the clinical competency of nursing
      students receiving field training in cardiac care units(CCU).

PMID- 23555111
TI  - Phenomenological explanation of an experiential curriculum in medical education:
      A feministic approach.
AB  - INTRODUCTION: This study addresses the design and validation of the experiential
      curriculum model for medical education using a Feministic approach. METHOD: The
      present study was conducted on two non separable planes. On the first plan, the
      model was designed based on the Feministic approach using the theoretical study
      method and emphasizing the perspectives ascribed to Nell Noddings, Madeline
      Grumet and Janette Miller. RESULTS: The levels of this model include Expected
      Curriculum, Imaginal Curriculum, Concealed curriculum, Interactive curriculum
      (Manifest Curriculum, Latent Curriculum, Look the parenting), Transferential
      Curriculum and Self Determination. On the second plane, to validate the combined
      model, a phenomenologically qualitative study was conducted. In this study, using
      goal-oriented sampling, undergraduate and graduate (Master's degree) students
      majoring in Dentistry, Nursing at Islamic Azad University Khorasgan Branch,
      Esfahan as well as those at at Esfahan University of Medical Sciences were
      selected. Deep interview was used to collect data. The findings were analyzed
      using Van Manen's six-stage model. To determine the reliability of the findings,
      reliability of reality reconstruction were used. CONCLUSION: THE RESULTS OBTAINED
      SUGGESTED THAT: Education is in need of some conceptual reconstruction. On this
      way, women's perceptions and experience of education and of the interior
      epistemological and curricular system which shape the discourse and performance
      of education must be addressed. Serving as a research model offering the various
      planes of the experiential curriculum and focusing more sharply on the dimensions
      of curriculum than the formal plane, the present study is recommended to the
      decision-makers of higher education curricular system.

PMID- 23555112
TI  - Marketing information goods and services in medical libraries and information
      centers.
AB  - Marketing is one of the essential parts of any business corporation in the modern
      management. One can see the difference between corporations in gaining their
      goals, considering their marketing methods. Gaining more advantage or acquiring
      more funds can be of reasons for marketing, but these are not all the reasons.
      Perhaps the most important reason for marketing is increasing the customer
      satisfaction. This, in turn, leads to more willingness in payment and using
      services. Nowadays, due to rapid growth in ICT, changes in budgets, rapid growth
      in development and use of knowledge, variety of users and their needs, marketing
      has become an important factor in any library activities. Libraries are now more
      responsible in this regard, because marketing is now an important tool in
      improving users' satisfaction in using library services. Hence, marketing is now
      very important for libraries to survive in the increasing pressures of
      competitive conditions of the information market. This article is tapping on
      issues such as information marketing, principles of marketing, marketing
      techniques, developing markets, and marketing skills. Some recommendations are
      also presented for marketing in libraries.

PMID- 23555113
TI  - A comprehensive test of clinical reasoning for medical students: An olympiad
      experience in Iran.
AB  - BACKGROUND: Although some tests for clinical reasoning assessment are now
      available, the theories of medical expertise have not played a major role in this
      filed. In this paper, illness script theory was chose as a theoretical framework
      and contemporary clinical reasoning tests were put together based on this
      theoretical model. MATERIALS AND METHODS: This paper is a qualitative study
      performed with an action research approach. This style of research is performed
      in a context where authorities focus on promoting their organizations'
      performance and is carried out in the form of teamwork called participatory
      research. RESULTS: Results are presented in four parts as basic concepts,
      clinical reasoning assessment, test framework, and scoring. CONCLUSION: we
      concluded that no single test could thoroughly assess clinical reasoning
      competency, and therefore a battery of clinical reasoning tests is needed. This
      battery should cover all three parts of clinical reasoning process: script
      activation, selection and verification. In addition, not only both analytical and
      non-analytical reasoning, but also both diagnostic and management reasoning
      should evenly take into consideration in this battery. This paper explains the
      process of designing and implementing the battery of clinical reasoning in the
      Olympiad for medical sciences students through an action research.

PMID- 23555115
TI  - The effects of suburban villages' health volunteer plan on women's health
      knowledge and attitude.
AB  - BACKGROUND: To achieve stable social development, the cooperation of all members
      of a -community is basically required. Providing and improving the health
      standard is one of the most fundamental dimensions of human social evolution.
      This is more essential than the other aspects of development (public cooperation
      demands) and health volunteers are the forerunners of this cooperation, who have
      voluntarily set about having the public participate in providing and elevating
      the level of community health. The present study aimed to determine the effect of
      implementing "the health communication plan" by health volunteers in suburban
      villages regarding the health knowledge and attitude of rural women. MATERIALS
      AND METHODS: In this quasi-experimental study, knowledge and attitude of 121
      females (age 15-49 years), who were under the supervision of health centers in
      four suburban villages (the case group), before and after performing the health
      volunteer plan, were compared to those of 94 females (age 15-49 years) in another
      group of four suburban villages (the control group) lacking health volunteers
      under the care service of two rural health centers. Data gathering instrument was
      questionnaires and interviews. The obtained data were analyzed by SPSS (ver.
      11.5) using statistical paired t-test and Sign test. P<=0.05 was considered to be
      statistically significant. RESULTS: The study showed that the mean of rural
      women's health knowledge and attitude had increased and there was a significant
      difference between before intervention and after intervention values in the two
      groups (P<0.001). Comparing the averages of the two groups also revealed a
      significant difference (P<0.001). CONCLUSIONS: According to the findings and the
      positive effects of performing suburban health volunteer plan on the health
      knowledge and attitude of rural women, it would therefore be important to suggest
      that suburban health volunteers are very helpful and effective in improving the
      knowledge and attitude level of rural women. In brief; as a direct result of
      their health performance, performing the plan all over rural health centers is
      recommended.

PMID- 23555114
TI  - Effectiveness of breastfeeding education on the weight of child and self-efficacy
      of mothers - 2011.
AB  - BACKGROUND: Breastfeeding is the most natural and essential way for feeding
      newborn babies. This is an ideal approach for physical and emotional development
      of babies, as well as for the recovery of mothers. This study was aimed to
      determine the effect of breastfeeding education based on the health belief model
      (HBM) toward primiparous women. MATERIALS AND METHODS: In a case-control group,
      quasi-experimental study, 88 subjects were allocated in control and experimental
      groups. Subjects who were assigned to the experimental group were provided a
      program consisting of group education based on HBM during their prenatal period.
      Instrument for data gathering was made by the researchers and standard
      questionnaire from Dennis and Faux for Breastfeeding Self-efficacy Scale (BSES).
      Baseline interviews were conducted before delivery and follow-up visits were
      conducted after 30 days and at the fourth month after delivery. Data were
      analyzed using SPSS (version 16) with c(2), independent sample t-tests, and
      paired t-test. RESULTS: Mean age of pregnant women who participated in the study
      was 22 +/- 3.29 years. After the program, the experimental group had
      significantly better scores in terms of self-efficacy, knowledge, and attitude
      scores statistically. In the fourth month, the mean of child weight in the
      experimental group was significantly higher than that of the control group
      (P=0.001) and exclusive breastfeeding was significantly higher than in the
      control group (P=0.007). CONCLUSION: Prenatal education in this study based on
      HBM was successful, and knowledge, attitude, self-efficacy, and related
      indicators improved. The necessity of producing standard education package and
      education of pregnant mothers, especially in their first pregnancy, by health
      professionals is perceived.

PMID- 23555116
TI  - Predicting mammography stage of adoption among Iranian women.
AB  - OBJECTIVE: Despite evidence that screening for breast cancer is effective,
      adherence with screening recommendations in Iranian women is low. The purposes of
      this study were to (1) identify the associations between individual
      characteristics, related health beliefs, and stages of mammography behavior and
      (2) examine the socio-demographic factors and the health beliefs that predicate
      stages of mammography behavior. DESIGN: All health care centers were considered
      as clusters and 30 women were randomly selected from each of them. A sample of
      689 Iranian women completed a questionnaire. MATERIALS AND METHODS: The
      questionnaire used was based on Champion's revised Health Belief Model Scale
      (CHBMS). One-way analysis of covariance (ANCOVA) was used to assess differences
      in the outcome variables (perceived severity, susceptibility, benefits, and
      barriers) across the stages. Multinomial logistic regression was conducted to
      test multivariate relationships. RESULTS: THE PERCENTAGE OF PARTICIPANTS IN EACH
      STAGE WAS: 40.1% in pre-contemplation, 34.7 in contemplation, 7.5% in relapse,
      12% in action, and 5.7% in maintenance stage of mammography adoption. Older women
      were most likely to be in the pre-contemplation stage and action stage, and the
      youngest women were most likely to be in the relapse stage. Differences across
      stages of change were found for related beliefs for all participants except those
      in the relapse stage. CONCLUSION: Iranian women are less likely to be in
      maintenance and action stages than ot er Asian women and this study identifies
      constructs that may be targeted in interventions.

PMID- 23555117
TI  - Effect of Health Belief Model based intervention on promoting nutritional
      behaviors about osteoporosis prevention among students of female middle schools
      in Isfahan, Iran.
AB  - BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by
      reduction of one mass, deterioration of bone structure, increasing bone
      fragility, and increasing fracture risk. Prevention of osteoporosis during
      childhood and adolescence is one of the most important issues in World Health
      Organization. The purpose of this study was to determine the effect of Health
      Belief Model based intervention on promoting nutritional behaviors about
      preventive osteoporosis among the second grade middle school girl students.
      MATERIALS AND METHODS: This was an experimental intervention study, the research
      population being 130 students who were randomly divided into groups, experimental
      (66) and control (64). Before the educational program, Health Belief Model based
      standard questionnaire and Food Frequency Questionnaire (FFQ) questionnaire were
      filled up by both the groups. The standard questionnaire was completed three
      times (before, immediately, and 2 months after education) and FFQ questionnaire
      was completed two times (before and 2 months after education) by the students.
      After pre-test, four educational session classes in the experimental group were
      performed. Finally, data collected were analyzed by SPSS 18 computer software.
      RESULTS: The result of this study showed a significant increase in the mean score
      of knowledge, perceived susceptibility, seriousness, benefits, barriers, as well
      as taking health action among girl students in the experimental group.
      CONCLUSION: The findings of the present study confirmed the practicability and
      effectiveness of the Health Belief Model based educational program in promoting
      nutritional behaviors about prevention of osteoporosis.

PMID- 23555118
TI  - The survey of nurse's knowledge and attitude toward cancer pain management:
      Application of Health Belief Model.
AB  - BACKGROUND: Effective cancer pain management requires accurate knowledge,
      attitudes, and assessment skills. The purpose of this study was to obtain
      information about the knowledge and attitudes of nurses concerning cancer pain
      management with the use Health Belief Model (HBM) as conceptual framework.
      MATERIALS AND METHODS: The study was a descriptive survey and included 98
      randomly selected nurses from Alzahra hospital, Isfahan, Iran. A self
      administered questionnaire which was designed on the basis of HBM was used to
      collect the data. Knowledge, attitudes, and HBM constructs regarding cancer pain
      were the main research variables. The obtained data were analyzed by SPSS
      (version11.5) using descriptive statistics, independent t-test, and Pearson
      correlation at the significant level of alpha=0.05. RESULTS: Ninety-eight nurses
      aged 38.7 +/- 7.04 years were studied in this survey. From the 10 pain knowledge
      questions assessed, the mean number of correctly answered question was 61.2
      (SD=16.5), with a range of 30-100. There was a direct correlation between
      knowledge and attitude of nurses with HBM constructs except for perceived
      barriers and perceived threat. Among the HBM constructs, the highest score was
      related to self-efficacy with mean score of 87.2 (SD=16.4). CONCLUSIONS: The
      findings support the concern of inadequate knowledge and attitudes in relation to
      cancer pain management. We believe that basic and continuing education programs
      may improve the knowledge level of nursing about pain management.

PMID- 23555119
TI  - Comparison of growth and nutritional evolution stages in infants with working
      mothers and infants with housewife mothers in Isfahan.
AB  - BACKGROUND: Studies have shown that the growth status of the children with
      working mothers is about 2 standard deviations lower than that of the children of
      housewife mothers. It seems that absence of mothers in the second stage of
      nutritional evolution (attachment), which is a very sensitive stage, has an
      important role in initiating and continuation of an appropriate supplemental
      feeding. MATERIALS AND METHODS: In this cross-sectional study, 50 children of
      working mothers and 50 children of housewife mothers were selected by non
      probable consecutive sampling method. Growth charts of the children in the two
      studied groups were assessed within seven age groups. Knowledge and attitude of
      the mothers regarding nutritional evolution stages in the two studied groups were
      assessed Obtained data were analyzed using Software SPSS18 and statistical tests
      such as chi-square, t-test, and Mann-Whitney test. RESULTS: Growth monitoring
      charts of the infants with housewife mothers were better than those of infants
      with working mothers in three out of seven age groups (12-18, 18-24, and 24-30
      months) (P=0.02). Mean of knowledge and performance of the mothers about
      nutritional evolution stages was not significant in the two studied groups
      (P>0.05). CONCLUSION: This study showed that growth status of children with
      housewife mothers in their second year of life was better than that of children
      with working mothers. Awareness and knowledge of the mothers about nutritional
      evolution stages and education of mothers about appropriate behaviors in each
      stage helped them to recognize the children's needs and did their best for their
      children.

PMID- 23555120
TI  - Related factors to choose normal vaginal delivery by mothers based on Health
      Belief Model.
AB  - BACKGROUND: Normal vaginal delivery (NVD) is the best method of delivery, but its
      rate is decreasing. Results of many studies have shown that the risk of cesarean
      section (CS) for both mother and child is more than that of NVD. The World Health
      Organization's (WHO) goal was to achieve a CS rate of 15% in 2010, but this rate
      in most of the developing countries is over than 50%. In this study, we try to
      determine the related factors influencing the method of delivery selection by
      mothers in Yazd city, Iran, based on Health Belief Model (HBM). MATERIALS AND
      METHODS: This was a cross-sectional study done on 130 pregnant women who
      presented in four clinics of Yazd. The mothers were in 32-37 weeks of gestational
      age. Samples were selected by simple randomized method. Data were collected by
      questionnaire by interviewing and then analyzed by analysis of variance (ANOVA)
      and t-test. RESULTS: Mean age of samples was 42.23 +/- 4.52 years. Eighty-four
      (64%) women were primigravids and 49 (37.7%) mothers were multigravids. Of them,
      the method of delivery in previous pregnancy was NVD in 29 (22.3%) and CS in 20
      (14.3%). In their present pregnancy, the method of delivery was NVD in 88 (67.7%)
      and CS in 42 (32.3%). The Pearson test showed a significant correlation between
      perceived barriers and behavior (P=0.012). Also, there was significant
      relationship between perceived susceptibility and behavior (P=0.03). There was no
      significant relation between other variables (perceived benefits and perceived
      severity). CONCLUSION: Based on the results of this study, perceived
      susceptibility and perceived barriers were related to behavior significantly, so
      we must educate mothers using HBM to influence their behavior toward selecting
      NVD as their delivery method.

PMID- 23555121
TI  - Factors associated with the fecal occult blood testing for colorectal cancer
      screening based on health belief model structures in moderate risk individuals,
      Isfahan, 2011.
AB  - BACKGROUND: Colorectal cancer is one of the most important and most common
      cancers and the second leading cause of cancer deaths worldwide. Every year,
      nearly 1 million new cases of colorectal cancer are recognized around the world
      and nearly half of them lose their lives due to the disease. The statistics
      reveal shocking incidence and mortality from colorectal cancer, therefore
      secondary prevention of this cancer is important and research has shown that by
      early diagnosis 90% of patients can be treated. Among the colorectal cancer
      screening tests, fecal occult blood test (FOBT) takes the priority because of its
      convenience and also low cost. But due to various reasons, the participation of
      people in this screening test is low. The goal of this study is to assess the
      factors that affect participation of population at average risk in colorectal
      cancer screening programs, based on health belief model structures. MATERIALS AND
      METHODS: A cross-sectional survey of 196 individuals, more than 50 years old, was
      conducted in Isfahan. Ninety-eight people of the target group were selected from
      laboratories while they came there for doing FOBT test; the method of sampling in
      this group was random sampling. The method of data collection in the other 98
      individuals was by home interview and they were selected by cluster sampling. The
      questionnaire used was based on health belief model to assess the factors
      associated with performing FOBT. The data collected were analyzed using
      descriptive and inferential statistical methods. RESULTS: The mean score of
      knowledge in the first group was 48/5 +/- 11/7 and in the second group was 36/5
      +/- 19/3. Individuals in the first group were more likely to be married, had more
      years of schooling, and better financial status. There were significant
      relationships between knowledge (P<0.001), perceived susceptibility (P<0.001),
      perceived severity (P<0.001), perceived barriers (P<0.001), and self-efficacy
      (P<0.001) in the two groups. There was no significant association between the
      perceived benefits in the two groups. Those people who have had FOBT test in last
      year in each group reported better score of Health Belief Model model structures.
      CONCLUSION: According to this study, it seems that there is an urgent need to pay
      more attention to this disease and its prevention through screening. With a
      better understanding of factors affecting the test, it can be a useful step to
      reduce the rate of death and costs, and improve the community health outcomes.

PMID- 23555122
TI  - Evaluation of self-care practices and relative components among type 2 diabetic
      patients.
AB  - BACKGROUND: The purpose of this study was to assess self-care practices and their
      relative components among type 2 diabetic patients. We hypothesized that some
      sociodemographic and health-related factors, high diabetes distress, and low self
      efficacy would be associated with poorer self-care practices. MATERIALS AND
      METHODS: A cross-sectional study was conducted for a period of 6 months in 2011.
      Study population was type 2 diabetic patients referring to Omolbanin center, an
      outpatient diabetic center in Isfahan. One hundred forty diabetic patients met
      the inclusion criteria and were all included in the study. Patients' self-care
      practices were measured by Summary of Diabetes Self-care Activities (SDSCA) self
      report scale that includes items on the following aspects of the diabetes
      regimen: General diet, specific diet, exercise, blood glucose testing, foot care,
      medications, and smoking. Diabetes distress measured by Diabetes Distress Scale
      (DDS) scale and Stanford diabetes self-efficacy scale was used for scoring this
      issue. Collected data were analyzed by using SPSS software version 11.5. RESULTS:
      Participants were between the ages of 37 and 75 years, with a mean of 53.23 years
      (SD=7.82). Fifty-four percent (n=76) were females; 97.1% were married (n=136),
      and 53.6% had education lower than diploma (n=75). Mean of duration of diabetes
      was 7.1 (SD=5.63) years. "Medications" subscale was considered as the most
      important one in measuring diabetes self-care practices (5.24 +/- 2.38
      days/week). Study findings revealed that general diet had significant relation
      with comorbidity, type of treatment, body mass index (BMI), fasting blood sugar
      (FBS), (Blood Sugar) (BS), waist circumference, diabetes distress, and self
      efficacy. Specific diet had significant relation with comorbidity, education,
      triglyceride (TG), diastolic blood pressure (DBP), and low density lipoprotein
      (LDL). Exercise showed significant relation with history of diabetes, education,
      type of treatment, disease duration, TG, BMI, and BS. Also, blood glucose testing
      showed significant relation with disease duration, self-efficacy, TG, DBP, BS,
      LDL, and high density lipoprotein (HDL). On the other hand, foot care was related
      to age, diabetes distress, TG, BMI, HDL, and diabetes complications. Medications
      subscale as the most important subscale of self-care practices was relevant with
      age, disease duration, diabetes complications, type of treatment, FBS, HDL, and
      self-efficacy. The last subscale, smoking, had significant relation with sex,
      diabetes complications, diabetes distress, self-efficacy, TG, total cholesterol,
      BS, and HDL. CONCLUSION: This information should be used in clinical practice
      when targeting and designing educational and care plan for patients with type 2
      diabetes.

PMID- 23555123
TI  - Development and psychometric testing of the Adolescent Healthy Lifestyle
      Questionnaire.
AB  - BACKGROUND: Lifestyle choices and individuals' behaviors have the potential to
      influence health and improve the quality of life. OBJECTIVES: The purpose of this
      study was to develop and psychometrically test an instrument for measuring
      healthy lifestyle in Iranian adolescents. MATERIALS AND METHODS: A comprehensive
      literature review related to health-promoting lifestyles was used to identify
      potential scale items. Data were collected from 797 school students. Construct
      validity was analyzed using exploratory factor analysis. Confirmatory factor
      analysis (CFA) was used to cross-validate. RESULTS: Nine factors emerged that
      explained 59.8% of the variance in the 43 items. Cronbach's alpha coefficient
      Healthy Lifestyle Questionnaire was r=0.82. After the model was modified, the fit
      indices indicated that the data were an adequate-to-good fit to the proposed
      models. CONCLUSIONS: The current study provides some support to the internal and
      external validity of the healthy lifestyles questionnaire for Iranian
      adolescents.

PMID- 23555124
TI  - Safety education and control: A tool to measure the safety locus of control.
AB  - BACKGROUND: Effective safety education can prevent many occupational accidents.
      To -educate the public about safety effectively, determinants of safe behavior
      must be addressed. Personality constructs are among the most important
      determinants of safe behavior. One of the personality constructs that has been
      studied recently in relation to accidents is locus of control. The main aim of
      this study was designing, validating, and determining the reliability of safety
      locus of control scale. MATERIALS AND METHODS: This study was a descriptive,
      cross-sectional study. The "forward-backward" procedure was applied to translate
      safety locus of control scale (Jones and Becker 1985) from English to Persian. To
      determine the scientific validity of the scale, face validity and content
      validity by expert judgments were used. Internal consistency was determined using
      Cronbach's alpha-coefficient. Questionnaires were distributed to a group of 400
      workers from different parts of Isfahan Steel Company. Finally, 317 workers
      completed the questionnaires. Exploratory factor analysis was performed with
      software SPSS13, and confirmatory factor analysis was performed with software
      LISREL8.8. RESULTS: The exploratory factor analysis results revealed that the
      three components of the items can be extracted from the scale including internal
      control (4 questions), environmental and equipment control (4 questions), and
      chance and fate (4 questions). Confirmatory factor analysis using maximum
      likelihood estimation results indicated that the data had good fit with three
      component scale and fit indices were acceptable: chi(2)/df=3.96, df=41, chi(2)
      =120.59, RMSIA=0.080, 95% Confidence Interval=0.64-0.097, CFI=0.96, GFI=0.94,
      AGFI=0.89. The internal control components and equipment and environmental
      control were negatively correlated with each other (P<=0.05, r=-0.41). Also, a
      weak correlation between chance and fate and environmental and equipment control
      was seen (P<=0.05, r=0.31). CONCLUSION: In most studies, designing a scale and
      determining its validity and reliability is costly and time consuming. The
      available reliable and valid scale leads to reduced costs and accelerated
      research. In other words, duplication will be avoided. The scale obtained in this
      study can be used in safety and industrial psychology research.

PMID- 23555126
TI  - Evaluating health literacy of Kerman Medical University, School of Public Health
      students about recycling solid waste.
AB  - BACKGROUND: The increasing trend in waste production and its improper disposal in
      the environment have led to mismanagement of national resources and hazards to
      the natural environment. Therefore, the recycling of solid waste can help prevent
      economic and bio-environmental disasters. The aim of this study was to evaluate
      the health literacy of the students of the Kerman Public Health School about the
      management and recycling of solid waste. MATERIALS AND METHODS: This was a cross
      sectional study and the target population was all of the students of the Kerman
      Public Health School (421 students) in five fields. A questionnaire including
      demographic and health literacy questions was distributed among the students.
      RESULTS: The male students answered the questions significantly more than female
      students (P<0.001). The Environmental Health students acquired a higher score
      than all other students and health literacy significantly increased as the
      student's studying degree promoted (P<0.001). Also, as the number of trimesters
      increased, health literacy significantly increased (P<0.001). The parents'
      education, the family income, and number of people in the family had no
      significant effect on health literacy. All students believed recycling is
      important and more than 50% had acquired their knowledge from their academics.
      CONCLUSION: This survey showed that although students in health-related fields
      confirm the necessity of recycling solid waste, they still need more education in
      health literacy as they are supposed to be the promoters of public health in the
      society in the near future.

PMID- 23555125
TI  - Smoking behaviors in Iranian male students: An application of transtheoretical
      model.
AB  - OBJECTIVE: To investigate selected constructs of the transtheoretical model (TTM)
      of behavior change regarding smoking behavior among Iranian male students.
      MATERIALS AND METHODS: A convenience sample of 578 smokers and ex-smokers from
      six universities during December 2009 to June 2010 completed three Persian
      versions of the short form smoking questionnaire based on TTM, developed by
      Prochaska, Velicer, and Diclemente. Data were analyzed using SPSS 15. Frequency
      analysis was conducted to demographic variables. Stages' differences were
      assessed with analysis of variance (ANOVA) followed by post-hoc multiple
      comparisons with Tukey's honestly significant difference (HSD) test. Alpha levels
      were set at P<0.05. RESULTS: More than half of the subjects were in contemplation
      stage. The pros of smoking among subjects in the precontemplation stage were
      significantly higher than those of subjects in the preparation and maintenance
      stages. Meanwhile; the pros of smoking ratings were significantly higher for the
      contemplation and preparation stages than for the maintenance stage. Significant
      mean differences in cons of smoking behavior emerged across the stages of change.
      However, pros and cons of smoking in the action stage were not significantly
      different than other stages of change. In line with self-efficacy/temptation
      construct, the result showed that positive social efficacy, negative affect
      efficacy, and habit strength were significantly different between the stages of
      change. CONCLUSION: The results provide support to the advantages of increased
      self-efficacy and the role of decisional balance for the intervention program
      development for smoking cessation.

PMID- 23555127
TI  - Determination of rate of customer focus in educational programs at Isfahan
      University of Medical Sciences(1) based on students' viewpoints.
AB  - BACKGROUND: Today, the challenges of quality improvement and customer focus as
      well as systems development are important and inevitable matters in higher
      education institutes. There are some highly competitive challenges among
      educational institutes, including accountability to social needs, increasing
      costs of education, diversity in educational methods and centers and their
      consequent increasing competition, and the need for adaptation of new information
      and knowledge to focus on students as the main customers. Hence, the purpose of
      this study was to determine the rate of costumer focus based on Isfahan
      University of Medical Sciences students' viewpoints and to suggest solutions to
      improve this rate. MATERIALS AND METHODS: This was a cross-sectional study
      carried out in 2011. The statistical population included all the students of
      seven faculties of Isfahan University of Medical Sciences. According to
      statistical formulae, the sample size consisted of 384 subjects. Data collection
      tools included researcher-made questionnaire whose reliability was found to be
      87% by Cronbach's alpha coefficient. Finally, using the SPSS statistical software
      and statistical methods of independent t-test and one-way analysis of variance
      (ANOVA), Likert scale based data were analyzed. RESULTS: The mean of overall
      score for customer focus (student-centered) of Isfahan University of Medical
      Sciences was 46.54. Finally, there was a relation between the mean of overall
      score for customer focus and gender, educational levels, and students' faculties.
      Researcher suggest more investigation between Medical University and others.
      CONCLUSION: It is a difference between medical sciences universities and others
      regarding the customer focus area, since students' gender must be considered as
      an effective factor in giving healthcare services quality. In order to improve
      the customer focus, it is essential to take facilities, field of study,
      faculties, and syllabus into consideration.

PMID- 23555128
TI  - Impacts of outsourcing in educational hospitals in Iran: A study on Isfahan
      University of Medical Sciences-2010.
AB  - PURPOSE: Outsourcing in healthcare is a cost-effective strategy that can lead to
      increase services quality. The aim of this study was to determine the types of
      services that have been outsourced in educational hospitals in Isfahan and to
      investigate managers' view about the impact of Outsourcing.
      DESIGN/METHODOLOGY/APPROACH: A descriptive-survey study carried out in 2010. Our
      samples consisted of 100 educational hospital and treatment deputy senior
      managers of Isfahan University of Medical Sciences and 53 usable questionnaires
      were received. Survey instrument main points were the extent to which educational
      hospital outsource services and the impact of Outsourcing. Reliability and
      validity of the questionnaire have been verified. Data are analyzed with SPSS18
      software. FINDINGS: The results for medical-diagnostics services showed
      physiotherapy, radiology, and ultrasound that have the highest rate (33%) of
      being outsourced. Between logistic and administrative activities, housekeeping,
      and facility engineering maintenance services are the highest rate of outsourced
      (100%) and green space, CSR, laundry, and medical records are the lowest rate of
      outsourced (16%). In managers' view, in relation to advantages of outsourcing,
      pay more attention to internal and external customers in private sector (57.2%)
      was the highest. In relation to disadvantages of outsourcing, costs increase for
      the patients (45.6%) was the highest. In relation to barriers of outsourcing,
      forgetting the goal of outsourcing (efficiency) (60.6%) was the highest.
      CONCLUSION: Finally, managers' views about outsourcing in health services
      organizations were rather acceptable, but in their views, there are barriers in
      implementation of outsourcing and they are focused on removing the barriers
      before outsourcing. Fundamental infrastructure developments as making competing
      market, promoting of cultures, education, modifying the management attitude and
      approach, and establishing incentive policies are emphasized for successful
      implementation of outsourcing.

PMID- 23555129
TI  - The comparative analysis of satisfaction rate among the public universities
      talented students with education and all the services provided to them.
AB  - INTRODUCTION: Universities provide different facilities for talented students.
      The aim of this research was to comparatively examine the rate of satisfaction
      among the talented students with the services offered to them at different
      Iranian universities. METHODS: This was a survey study in which a researcher-made
      questionnaire was used to collect the data. The statistical population of this
      research consisted of all the talented students at four universities who had been
      admitted at these universities from 2003 to 2009. Using the formula, the total
      number of samples was estimated to be approximately 328. RESULTS: The research
      findings indicated that the talented students did not have satisfaction with the
      educational situation, and no statistically significant difference was observed
      among the different universities with regard to this issue. CONCLUSION: According
      to the findings it is suggested that universities offer more financial facilities
      for research, and attending conferences, and provide rich-content and valuable
      classes, and active and creative teaching methods. It is also proposed that
      educational workshops on detecting talented students and the manner of dealing
      with them be convened for faculty members.

PMID- 23555130
TI  - A comparative study on the Earthquake Information Management Systems (EIMS) in
      India, Afghanistan and Iran.
AB  - CONTEXT: Damages and loss of life sustained during an earthquake results from
      falling structures and flying glass and objects. To address these and other
      problems, new information technology and systems as a means can improve crisis
      management and crisis response. The most important factor for managing the crisis
      depends on our readiness before disasters by useful data. AIMS: This study aimed
      to determine the Earthquake Information Management System (EIMS) in India,
      Afghanistan and Iran, and describe how we can reduce destruction by EIMS in
      crisis management. MATERIALS AND METHODS: This study was an analytical comparison
      in which data were collected by questionnaire, observation and checklist. The
      population was EIMS in selected countries. Sources of information were staff in
      related organizations, scientific documentations and Internet. For data analysis,
      Criteria Rating Technique, Delphi Technique and descriptive methods were used.
      RESULTS: Findings showed that EIMS in India (Disaster Information Management
      System), Afghanistan (Management Information for Natural Disasters) and Iran are
      decentralized. The Indian state has organized an expert group to inspect issues
      about disaster decreasing strategy. In Iran, there was no useful and efficient
      EIMS to evaluate earthquake information. CONCLUSIONS: According to outcomes, it
      is clear that an information system can only influence decisions if it is
      relevant, reliable and available for the decision-makers in a timely fashion.
      Therefore, it is necessary to reform and design a model. The model contains
      responsible organizations and their functions.

PMID- 23555131
TI  - Study of the relationship between socioeconomic status and controlling diabetes
      among patients admitted to specialized clinic of Dr. Gharazi hospital in Isfahan
      2011.
AB  - INTRODUCTION: Diabetes is one of the chronic diseases that have been considered
      by policy makers. Diabetes causes premature mortality, disability and sometimes
      irreversible problems. Although it is under consideration of doctors, there is no
      study about the role of the socioeconomic status of the patient in control of
      diabetes in our society. The main purpose of this research is to explore
      relationship between socioeconomic status and control of diabetes. MATERIALS AND
      METHODS: 320 diabetic patients were randomly chosen from specialized clinic of
      Dr. Gharazy hospital. The element was questionnaire which its reliability was
      calculated according to coefficients Cronbach's alpha (r = .078). The patients'
      two previous sessions' blood sugar level and also their HbA1C were studied via
      referring to their medical records. Then the patients were categorized into
      successful and unsuccessful groups in controlling the diabetes. Their
      socioeconomic status was analyzed through SPSS software. RESULTS: The findings
      show that there is a direct relationship between socioeconomic status and control
      of diabetes. The better socioeconomic status is the better diabetes has been
      controlled. CONCLUSION: In order to control diabetes, taking drugs and patients'
      socioeconomic status should be take into consider and social screening is
      essential.

PMID- 23555132
TI  - Fruit and vegetable intake, body mass index and waist circumference among young
      female students in Isfahan.
AB  - BACKGROUND: Obesity is growing rapidly in our country. Nutrition is an important
      issue of obesity. The aim of this study was to determine the association between
      fruit and vegetable intake with the waist circumference and the body mass index
      (BMI) among young female university students. MATERIALS AND METHODS: This cross
      sectional study was conducted on 236 healthy female university students aged
      between 18 and 30 years old, who were selected randomly from the students of
      Isfahan University of Medical Sciences, Iran. A previously validated semi
      quantitative food frequency questionnaire was used to assess the entire dietary
      component intake. Physical activity was assessed by daily recording of the
      physical activities. FINDINGS: The prevalence of obesity, central adiposity and
      overweight was 1.7, 0.9 and 8.1%, respectively. The mean value of BMI and the
      waist circumference was 21.54 kg/m(2) and 70.37 cm, respectively. There was an
      inverse correlation between the fruit and vegetable intake and body weight (r = 
      0.1, P = 0.03) as well as BMI (r = -0.1, P = 0.04) and also there was an inverse
      correlation between the fruit intake and body weight (r = -0.1, P = 0.01) and BMI
      (r = -0.1, P = 0.01). There was no significant correlation between fruit and
      vegetable as well as fruit or vegetable separately with the waist circumference.
      CONCLUSION: There were significant correlations between fruit and also fruit and
      vegetable and body weight and BMI among female university students. There was no
      significant correlation between fruit and vegetable as well as fruit or vegetable
      separately with waist circumference.

PMID- 23555133
TI  - Assessment of gamma-dose rate in city of Kermanshah.
AB  - INTRODUCTION: Environmental natural radiation measurement is of great importance
      and interest especially for human health. The induction of genetic disorder and
      cancer appears to be the most important in an exposed population. MATERIALS AND
      METHODS: Measurements of background gamma rays were performed using a mini-rad
      environmental survey meter at 25 different locations around the city of
      Kermanshah (a city in the west of Iran). The measurements were also performed at
      two different time of day one in the morning and the other in the afternoon. At
      each location and time measurements were repeated for five times and the mean was
      considered as the background dose at that location. RESULTS AND DISCUSSIONS:
      Comparison between the measured results in the morning and afternoon has not
      shown any significant difference (P > 0.95). The maximum and minimum obtained
      results were 2.63 mSv/y and 1.49 mSv/y, respectively. From the total measurements
      at 25 sites mean and SD background radiation dose to the population is 2.24 +/-
      0.25 mSv. CONCLUSION: The mean radiation dose to the population is about 2.5
      times of the world average total external exposure cosmic rays and terrestrial
      gamma rays dose reported by UNSCEAR.

PMID- 23555134
TI  - Relationship between health literacy, health status, and healthy behaviors among
      older adults in Isfahan, Iran.
AB  - BACKGROUND: Health literacy is a measure of an individual's ability to read,
      comprehend, and act on medical instructions. Limited health literacy can reduce
      the adults' ability to comprehend and use basic health-related materials, such as
      prescription, food labels, health education pamphlets, articles, appointment
      slips, and health insurance plans, which can affect their ability to take
      appropriate and timely health care action. Nowadays, low health literacy is
      considered a worldwide health threat. So, the purpose of this study was to assess
      health literacy level in older adults and to investigate the relationships
      between health literacy and health status, health care utilization, and health
      preventive behaviors. MATERIALS AND METHODS: A cross-sectional survey of 354
      older adults was conducted in Isfahan. The method of sampling was clustering.
      Health literacy was measured using the Test of Functional Health Literacy in
      Adults (TOFHLA). Data were collected using home interviewing. Health status was
      measured based on self-rated general health. Health care utilization was measured
      based on self-reported outpatient clinic visits, emergency room visits, and
      hospitalizations, and health preventive behaviors were measured based on self
      reported preventive health services use. RESULTS: Approximately 79.6% of adults
      were found to have inadequate health literacy. They tended to be older, had fewer
      years of schooling, lower household income, and were females. Inadequate health
      literacy was associated with poorer general health (P < 0.001). Health literacy
      level was negatively associated with outpatient visits (P = 0.003) and
      hospitalization (P = 0.01). No significant association was found between health
      literacy level and emergency room utilization. Self-reported lack of PSA
      (Prostate-Specific Antigen) test (P < 0.001) and fecal occult blood test (FOBT; P
      = 0.003) was higher among individuals with inadequate health literacy than those
      with adequate health literacy. No significant association was found between
      health literacy level and mammogram in the last 2 years. CONCLUSION: Low health
      literacy is more prevalent in older adults. It indicates the importance of health
      literacy issue in health promotion. So, with simple educational materials and
      effective interventions for low health literacy group, we can improve health
      promotion in the society and mitigate the adverse health effects of low health
      literacy.

PMID- 23555135
TI  - Exploring practice of Isfahan University of Medical Science students regarding
      using ecstasy based on health belief model in 2011.
AB  - INTRODUCTION: Ecstasy consumption has increased 70% worldwide, and its use is
      currently outweighed heroin and cocaine. Conducted survey found that students
      more than other groups used ecstasy pills. Ecstasy usage has recently augmented
      in students. Therefore, this study aims to determine practice of Isfahan
      University of Medical Science students about using ecstasy based on health belief
      model in 2011. MATERIALS AND METHODS: A cross-sectional study was conducted on
      267 students of Isfahan University of Medical Science. Data were collected by a
      validated and reliable questionnaire in 3 parts (demographic information, H.B.M
      constructs, and practice). To analyze, SPSS software (ver.18) and statistical
      test including T-Test and Kruskal-Wallis were used. RESULTS: The mean score of
      age was 20.95 +/- 1.61 years, and 39.3% of men and 90.6% of women were single.
      2.2% of students have used ecstasy pills. The mean score of H.B.M constructs was
      perceived susceptibility (72.75 +/- 19.68), perceived severity (84.58 +/- 16.98),
      and perceived benefits (80.43 +/- 23.49). The finding presented that there was
      significant differences between the using ecstasy and perceived severity and
      perceived benefits (P <= 0.001), but there was no significant statistical
      relationship between the using ecstasy and perceived susceptibility and perceived
      barriers (P = 0.076, P = 0.554). In terms of cues to action, students suggested
      that radio and TV are most significance cues. CONCLUSION: According to results,
      to prevent ecstasy usage among Isfahan University of Medical Science students
      based on health belief model, we should improve perceived susceptibility.
      Besides, radio and TV rules as the most important cues should not also be denied.
      Moreover, newly identified susceptibility indicates the need for quantitative
      research and behavioral trials.

PMID- 23555136
TI  - An examination of the effect of health promotion plan in high school students' on
      knowledge and performance on peers suffering from asthma in high schools of
      district 3 in Esfahan, 2010.
AB  - BACKGROUND: Asthma is the most prevalent disease during childhood, known as the
      most important reason for children's disability adolescences truancies, thanks to
      their hospitalization and as a result intensification of disease symptom.
      MATERIAL AND METHODS: The present study is quasi-experimental kind, implemented
      with two groups. Sampling method was straightforward. 80 student's second-grade
      high school students constitute participants. Both groups were homogenized
      considering age, gender, education, and parent's vocation. First of all, a letter
      agreement was received from students. Then, the knowledge and accomplishment of
      students were measured by means of relevant questionnaire and checklist in
      advance of educational intervention. In the next step, during 4 sessions,
      educational content specified beforehand was presented to students via interview,
      lecture, group discussion, and display methods. The knowledge and accomplishment
      of both groups' students was measured through questionnaire and checklist.
      Finally, the data was analyzed by SPSS 16 and statistical test of t-paired,
      independent-t, man-Whitney, and ANOVA. RESULTS: The finding demonstrated that
      group's student accomplishment registered 91.8 +/- 1.3 while being 2.2 +/- 0.6
      before holding session. In addition, their knowledge increased significantly,
      registering 99.6 +/- 1.2 while it had measured as 1.3 +/- 0.3 before sessions.
      The results of paired t-test indicated that the average of difference between
      knowledge and accomplishment grades of two groups was significant (P<0.05).
      CONCLUSIONS: Regarding the finding of the present study and the fact that asthma
      is on the rise resulting in an increase in truancies as well as stressing the
      efficacy of training peers suffering from the disease, the implementation of the
      curriculum could be necessary.

PMID- 23555137
TI  - Adolescent brushing and its association with parents' socio-economic status.

PMID- 23555138
TI  - The introduction of self-management in Type 2 Diabetes care: A narrative review.
AB  - Type 2 diabetes is one of the most life-threatening public health challenges in
      the world. It causes a high disease burden including increased disability,
      reduced life expectancy and ever-increasing costs of care in almost every
      country. The growing burden of diabetes along with rapid cultural changes, aging
      population, increasing urbanization, changes in nutritional habits, reduced
      physical activity, and improper lifestyle and behavior patterns would inexorably
      drive increased health care costs and demands. Several models of education have
      been proposed to reduce the complications of chronic diseases including diabetes.
      However, it is widely known and acknowledged that adopting self-care and self
      management behaviors play a fundamental role in diabetes control and treatment. A
      non-systematic (narrative) search strategy was used to collect necessary data.
      Several models of diabetes care such as compliance-based or curative models
      exist. Neither the curative model nor the compliance/adherence model is
      rigorously effective in diabetes care. The model of self-empowerment - based on
      the three fundamental aspects of chronic illness care: choices, control, and
      consequences - is much more applicable in the management of diabetes. This point
      to an approach which recognizes that patients are responsible for their diabetes
      care. Self-empowerment model has the potential to place diabetes care into
      context - a context which is based on active involvement of patients and
      informed, proactive healthcare professionals in the process of care.

PMID- 23555139
TI  - Study of knowledge and attitude regarding prenatal diagnostic techniques act
      among the pregnant women at a tertiary care teaching hospital in Mumbai.
AB  - BACKGROUND: Sex ratio, an important social indicator measuring extent of
      prevailing equity between males and females in society, is defined as number of
      females per 1000 males. Changes in sex ratio reflect underlying socioeconomic,
      cultural patterns of a society. As per 2011 census sex ratio in India is 914/1000
      males, which continues to be significantly adverse towards women. OBJECTIVES:
      This study was conducted to assess the knowledge and attitude regarding Prenatal
      Diagnostic Techniques (PNDT) Act among the pregnant women at a tertiary care
      teaching hospital in Mumbai. MATERIALS AND METHODS: A cross-sectional study was
      carried out in the antenatal ward of Lokmanya Tilak Municipal Medical College and
      General Hospital, Mumbai during the period of January to April 2008. A total of
      143 women were included and a pre-designed and pre-tested questionnaire was used
      to get information regarding socio-demographic details of the pregnant women.
      They were asked regarding the knowledge and attitude towards the PNDT Act. Data
      was analyzed by using Statistical Package of Social Sciences (SPSS) 16.0.
      RESULTS: In the present study, out of 143 women, 105 (73.5%) knew about sex
      determination. Even out of those who had heard, the correct knowledge regarding
      PNDT act was very less. Sonography as a technique for sex determination done at
      private hospital was known to the majority of women. CONCLUSION: Education of
      women about gender equality and recommendations under PNDT act in order to
      improve declining sex ratio in our country must be done. Wide publicization in
      the media of the Act must be scaled up.

PMID- 23555140
TI  - Mammography stage of adoption among Iranian women.
AB  - BACKGROUND: Stage of Change and Health Belief Models are two the most common
      models that have been applied in mammography screening behaviors. The purpose of
      this study was to identify women in different stages of mammography adoption and
      to examine association between women's beliefs by stage of change among Iranian
      women. METHODS: In this population-based study, mammography screening behavior
      determined using the Rakoweski stage of change scale, and women beliefs were
      determined by Farsi version of Champion's Health Belief Model scale (CHBMS). The
      obtained data were analyzed by SPSS (version 16.0) using statistical analysis of
      variance and Chi-square tests that used to determine relation between socio
      demographic variables and HBM scales with stage of mammography. In all of the
      tests, a significant level alpha = 0.05 was considered. RESULTS: According to
      stages of change distributions for mammography screening behavior, 36.2% were in
      pre-contemplation, 21.1% in contemplation, 4.2% in action, 6.2% in maintenance,
      and 32.3% were in relapse stage. There were significant differences in
      mammography stage by age, education, married status, family monthly income,
      husband job, information about breast cancer, and history of breast problems.
      ANOVA test showed significant differences by stages for all HBM scales, except to
      perceived severity. CONCLUSION: The findings indicated that women in pre
      contemplation, relapse, and contemplation stages are more likely need to
      educational intervention, which emphasizes the benefits and barriers of
      mammography, health motivation, and self-efficacy. Furthermore, examining
      individuals' beliefs about breast cancer and mammography screening by stage of
      mammography adoption is especially important in order to development of
      effectiveness interventions, which targeted to stage of change and promote
      mammography screening behavior.

PMID- 23555141
TI  - Effects of "Teaching Method Workshop" on general surgery residents' teaching
      skills.
AB  - INTRODUCTION: Residents have an important role as teachers and need to know about
      teaching, teaching methods and skills. In developed countries, "resident-as
      teacher" programs have been implemented progressively; but there is little
      information about this theme in developing countries such as Iran. This study
      aimed to determine effects of "teaching method" workshop on surgical residents'
      teaching skills in Isfahan University of Medical Sciences. MATERIALS AND METHODS:
      In this quasi-experimental study, 18 residents in 1(st), 2(nd), and 3(rd) years
      of surgical residency in Isfahan University of Medical Sciences have attended in
      a 10-hour workshop. Two questionnaires (validity and reliability) was verified:
      Clinical teaching self-assessment and clinical teaching evaluation was completed
      before and after the intervention ("teaching method" workshop) by attending
      residents and rater interns, respectively. Paired-samples T-test was used to
      analyze collecting data. RESULTS: After intervention, Self-assessment mean scores
      were increased in two categories: feedback from 3.34 to 3.94 (P = 0.011) and
      promoting self- directed learning from 3.53 to 4.02 (P = 0.009); whereas, there
      was no significant differences in evaluation mean scores. CONCLUSION: Statistical
      results from self-assessment and evaluation scores show little improvement in
      residents' teaching skills after the intervention, but residents assessed the
      workshop as useful. Lack of motivation in interns and little reward for residents
      who attend in educational activities could be responsible for these results. So,
      to promote role of residents' as teachers, we offer revision in residency
      curriculum and residents' formal duties as well as designing educational programs
      in teaching theme based on our needs and resources.

PMID- 23555142
TI  - Medical tourism in Iran: Issues and challenges.
AB  - INTRODUCTION: Medical tourism is rapidly becoming a worldwide, multibillion
      dollar industry. Iran has a high potential for this industry. The purpose of this
      study was to examine the medical tourism cluster, using Diamond Analysis tool.
      MATERIALS AND METHODS: This study is a descriptive, analytical and qualitative
      one. Thirty professionals and researchers in this field were interviewed and
      official documents belonging to the Health ministry as well as tourism
      organization and finally related literature were examined. The data was analyzed
      using content analysis method. RESULTS: Positive and negative parts of the
      medical tourism industry of Iran were determined according to diamond of
      advantage. CONCLUSION: The strategic issues were identified and a number of
      possible solutions for addressing them were recommended. More and effective
      public-private participations, aggressive marketing, improving infrastructures,
      and international accreditation of health care facilities and human resources
      development could improve medical tourism industry in the country.

PMID- 23555144
TI  - Health literacy of Kerman Medical University, school of public health students
      about recycling solid waste.
AB  - INTRODUCTION: The increasing trend in waste production and its improper disposal
      in the environment have led to mismanagement of national resources and hazards to
      the natural environment. Therefore the recycling of solid waste can help prevent
      economic and bioenvironmental disasters. The aim of this study was to evaluate
      the health literacy of the student of the Kerman Public Health School, about the
      management and recycling of solid waste. METHODS: This was a cross-sectional
      study and the target population was all of the students of the Kerman Public
      Health School (421 students), in five fields. A questionnaire including
      demographic and health literacy questions was distributed among the students.
      RESULTS: The male students answered the questions significantly more than female
      students (P < 0.001). The Environmental Health students acquired a higher score
      than all other students and health literacy significantly increased as the
      student's studying degree promoted (P < 0.001). Also as the number of trimesters
      increased, health literacy significantly increased (P < 0.001). The parents'
      education, the family income and number of people in the family had no
      significant effect on health literacy. All students believed recycling is
      important and more than 50% had acquired their knowledge from their academics.
      CONCLUSION: This survey showed that students in health related fields although
      confirm its necessity, but need more education in health literacy as they are
      supposed to be the promoters of public health in the society in the near future.

PMID- 23555143
TI  - Investigating and comparing energy and macronutrient intake in female aerobic
      athletes in two different socio-economic regions.
AB  - BACKGROUND: The purpose of this study was to assess nutritional intakes of female
      aerobic athletes in two different socio-economic classes in city of Isfahan.
      MATERIALS AND METHODS: The participants of this analytical study were 99 female
      aerobic athletes aged between 15 and 50 years old who were randomly sampled (50
      females in low economic region and 49 females in high economic region). The
      demographic details were collected by a questionnaire, and anthropometric indexes
      including height, weight, and waste circumference were measured using a tape
      measure and a scale. They filled out the 24-hour food recall questionnaire for
      two consecutive days in order to obtain their nutritional information. To analyze
      the data, Nutritionist 4 and SPSS18 software were used. RESULTS: The means of
      energy intake in high and low regions were 1479.19 +/- 561.86 and 1300.68 +/-
      498.354 kcal, respectively. There was no significant difference in terms of
      energy intake between these two groups (P = 0.98). The means of protein intake in
      low and high socio-economic classes were 17.41 +/- 5.85 and 54.48 +/- 6.62,
      respectively, and no significant differences were observed between these two
      regions (P = 0/606). The means of carbohydrate intake were 61.85 +/- 9.76 and
      54.48 +/- 6.62 in the low and high socio-economic classes with a significant
      difference between them (P < 0.001). The mean of carbohydrate intake in the low
      socio-economic class was considerably higher than that in the high socio-economic
      class. The means of fat intake were 23.88 +/- 8.24% and 30.07 +/- 6.68% in the
      low and high socio-economic classes, respectively, and the means of fat intake in
      the high socio-economic region was significantly higher than that in the low
      socio-economic region (P < 0/001). CONCLUSION: The findings of this study
      indicated that the intakes of fat and carbohydrate were significantly different
      in the two different socio-economic regions in city of Isfahan. This difference
      could be attributed to different food patterns in these two regions.

PMID- 23555145
TI  - Knowledge, attitude and performance of academic members regarding effective
      communication skills in education.
AB  - BACKGROUND: Communication is the most important part of any educational process,
      the aim of which is to transfer or exchange ideas and thoughts. It would be
      provided appropriately if academic members had the communication skills.
      Considering the important role of academic members in the educational process, in
      this study, the knowledge, attitude and performance of academic members of School
      of Health, Isfahan University of Medical Sciences, were investigated with regard
      to effective communication skills. MATERIALS AND METHODS: In this descriptive
      analytic study, all academic members of the School of Public Health, Isfahan
      University of Medical Sciences, were studied during the second academic semester
      of 2006-2007. The data were collected by a valid and reliable three-part
      questionnaire including knowledge (8 questions and maximum score of 8), attitude
      (31 questions and maximum score of 155) and observational communication skills
      checklist (20 questions and maximum score of 20). The obtained data were analyzed
      by calculating central indices using SPSS software. FINDINGS: The mean knowledge
      score of studied people in terms of communicational skills, attitude and
      performance were 4.1 out of 8, 114.4 out of 155 and 16.3 out of 20, respectively.
      CONCLUSION: Although the information of the participants of this study in terms
      of communication skills was not sufficient, they seemed to have a positive
      attitude and relatively acceptable performance in communication skills.

PMID- 23555146
TI  - Designing and evaluation of the teaching quality assessment form from the point
      of view of the Lorestan University of Medical Sciences students - 2010.
AB  - INTRODUCTION: Education is basically one of the Universities' and faculties'
      leading missions and duties; its promoted quality will also lead to an elevated
      educational quality in the University. Teacher assessment can be mentioned as
      essential for the success of the quality promotion process. This article deals
      with the designing and evaluation of a teaching quality evaluation form for
      teachers, from the Lorestan University of Medical Science students' point of
      view. METHODS: A two-stage, cross-sectional study was conducted on 290 Lorestan
      University of Medical Science students. First, evaluation priorities were
      extracted using the Delphi technique in the fifth section, including teaching
      skills, communication skills, principles of training, and skills assessment. In
      the second stage, as the priority and importance of each item was evaluated in
      the fourth Lickert option, sampling was done in few stages. The study instrument
      was a questionnaire, which included six areas. The first part of the
      questionnaire was made up of the demographic characteristics and the second part
      included five evaluation areas that were obtained from the student. The collected
      data were analyzed using statistical software SPSS-16 and chi-square test,
      Kruskal-Wallis test. RESULTS: In the areas of teaching skills, mastery of the
      course, individual characteristics, self-confidence, communication skills,
      intimate relationship with students, educational principles, rules respecting the
      beginning and end time of class, skill assessment, and an accurate comprehensive
      examination at the end of the semester by the students, were chosen as the most
      important factors. There were significant differences in the majority of
      expressed comments between the genders and academic status (P < 0.05).
      CONCLUSION: Students can properly diagnose the essential factors in teachers'
      evaluation, but in item prioritizing they may be partly affected by some factors
      such as gender, academic status, semester, and academic course.

PMID- 23555147
TI  - Case fatality rates of different suicide methods within Ilam province of Iran.
AB  - BACKGROUND: There are few diverse studies that have reported the case fatality
      rates of different methods of suicide, none of them are originated from
      developing countries. The aim of the present article is to report the case
      fatality rates of different methods of suicide in Ilam province of Iran.
      MATERIALS AND METHODS: Data on 611 cases of suicide and 1807 cases of deliberate
      self harm (DSH) that were recorded in a comprehensive registry during 1995
      through 2002 were analyzed for both genders together and for males and females,
      separately. FINDINGS: For both genders together, the two most fatal methods were
      hanging (75.4%) and self-immolation (68.3%); for males, hanging (76.3%) and self
      immolation (64.7%); and for females, firearms (75%) and hanging (73.7%),
      respectively. The least fatal methods for both genders together and for females
      and males separately were drug ingestion and cutting. CONCLUSION: The results of
      present study, which for the first time has reported the case fatality rates of
      suicide methods in a developing world, would not only help to better plan the
      local suicide prevention strategies and clinical assessment of suicidal cases but
      to shed light on overall understanding of this mysterious human phenomenon.

PMID- 23555148
TI  - Quality gap in primary health care services in Isfahan: women's perspective.
AB  - BACKGROUND: Quality gap is the gap between client's understanding and
      expectations. The first step in removing this gap is to recognize client's
      understanding and expectations of the services. This study aimed to determine
      women's viewpoint of quality gap in primary health care centers of Isfahan.
      MATERIALS AND METHODS: This cross-sectional study was conducted on women who came
      to primary health care centers in Isfahan city. Sample size was 1280 people.
      Service Quality was used to collect data including tangible dimensions,
      confidence, responsiveness, assurance and sympathy in providing services. Data
      were analyzed by t test and chi square test. RESULTS: The results showed that
      women had controversy over all 5 dimensions. The least mean quality gap was seen
      in assurance (-11.08) and the highest mean quality gap was seen in tangible
      dimension (-14.41). The difference between women's viewpoint in all 5 dimensions
      was significant. (P < 0.05). CONCLUSION: Negative difference means clients'
      expectations are much higher than their understanding of the current situation,
      so there is a large space to improve services and satisfy clients.

PMID- 23555149
TI  - Healthy lifestyle in teachers.
AB  - INTRODUCTION: The role of individual healthy behaviors like physical activity,
      nutrition and stress management on reduction of rate of disease mortality and
      morbidity is well known. The aim of this study is to determine healthy life style
      in teachers employed in district No.4 in Isfahan, Iran, in 2010. MATERIALS AND
      METHODS: The participants of this cross-sectional study were 96 teachers in
      district No. 4, selected via random sampling method. The data collection was
      performed using a questionnaire including demographic healthy lifestyle
      questions. Analysis of the data was performed through Software SPSS version 18.
      RESULTS: The mean age of the subjects was 40.26 +/- 6.05 years and, BMI mean was
      25.08 +/- 3.20. 96.8% of them were married and 3.1% also were single. 1% of the
      teachers had a weak lifestyle, 13.5%had moderate, 85.4% had a good lifestyle. In
      terms of nutrition, 2% of the teachers had a weak lifestyle, 23% moderate, 74%
      good. 76% in terms of physical activity, 29.2% smoking and 21.9% stress had a
      weak lifestyle. CONCLUSION: According to the results, planning for teachers in
      school for receiving information about healthy lifestyle is important.

PMID- 23555150
TI  - Smoking behavior, nicotine dependency, and motivation to cessation among smokers
      in the preparation stage of change.
AB  - OBJECTIVE: To investigate selected constructs of the transtheoretical model (TTM)
      of behavior change regarding smoking behavior among people in the preparation
      stage, as well as motivation for cessation and nicotine dependency. METHODS: A
      convenience sample of 123 smokers, during between June to and September 2011,
      completed the Persian version of the short form of a smoking questionnaire based
      on TTM, the Fagerstrom nicotine dependence test, and the motivational test.
      RESULTS: Motivation for cessation was great (16.35 +/- 2.45). The negative
      affects of self-efficacy were higher than those to other situations (4.02 +/-
      0.84). The pros and cons of smoking were 2.69 +/- 1.00 and 3.78 +/- 0.78,
      respectively. Temptation was influenced by nicotine dependency (P < 0.05). Early
      initiation of smoking was significantly associated with severe nicotine
      dependency (P < 0.05). CONCLUSION: The results confirm the role of temptation,
      increase in the cons, decrease in the pros, and nicotine dependency.

PMID- 23555151
TI  - Stress Degradation Studies of Tebipenem and a Validated Stability-Indicating LC
      Method.
AB  - A inexpensive and rapid isocratic LC method has been developed for the
      quantitative determination of tebipenem-a new beta-lactam antibiotic. Stress
      degradation studies were performed on tebipenem in acidic (0.2 N hydrochloric
      acid) and basic (0.02 N sodium hydroxide) solutions, in a solution with oxidizing
      agent (3 % hydrogen peroxide), and in the solid state, during thermolysis and
      photolysis. For a chromatographic separation of tebipenem and its degradation
      products, a C-18 stationary phase and 12 mM ammonium acetate-acetonitrile (96:4
      v/v) were used. A quantitative determination of tebipenem was carried out by
      using a PDA detector at 298 nm, with a flow rate of 1.2 mL min-1. The linear
      regression analysis for the calibration plots showed a good linear relationship
      (r = 0.999) in the concentration range 0.041-0.240 mg mL-1. The method
      demonstrated good precision (1.14-1.96 % RSD) and recovery (99.60-101.90 %). The
      limits of detection and quantitation were 9.69 and 29.36 MUg mL-1, respectively.
      The analysis of tebipenem reactivity was supported by quantum chemical
      calculations based on the density functional theory (DFT). The analysis of the
      electron density of the HOMO and LUMO of tebipenem suggested the possibility of
      electron transport in the molecule during the degradation of bi-cyclic 4:5 fused
      penem rings.

PMID- 23555152
TI  - Stability-Indicating HPLC Method for the Determination of Cefcapene Pivoxil.
AB  - The stability-indicating LC assay method was developed and validated for
      quantitative determination of cefcapene pivoxil in the presence of degradation
      products formed during forced degradation studies. An isocratic RP-HPLC method
      was developed with a Lichrospher RP-18 (250 mm * 4.6 mm, 5 MUm) column and the
      mobile phase composed of 45 volumes of acetonitrile and 55 volumes of mixture
      composed of citric acid 10 mmol L-1 and potassium chloride 18 mmol L-1. The flow
      rate of the mobile phase was 1 mL min-1. Detection wavelength was 270 nm and
      temperature was 30  degrees C. Cefcapene pivoxil, similar to other
      cephalosporins, was subjected to stress conditions of degradation in aqueous
      solutions including hydrolysis, oxidation, and thermal degradation. The method
      was validated with regard to linearity, accuracy, precision, selectivity, and
      robustness. The method was applied successfully for the determination of
      cefcapene pivoxil during kinetic studies in aqueous solutions (pH and thermal
      degradation) and in solid state (oxidative, thermal, and radiolytic degradation).

PMID- 23555153
TI  - Catalysis in the Service of Green Chemistry: Nobel Prize-Winning Palladium
      Catalysed Cross-Couplings, Run in Water at Room Temperature: Heck, Suzuki-Miyaura
      and Negishi reactions carried out in the absence of organic solvents, enabled by
      micellar catalysis.
AB  - Palladium-catalysed cross-couplings, in particular Heck, Suzuki-Miyaura and
      Negishi reactions developed over three decades ago, are routinely carried out in
      organic solvents. However, alternative media are currently of considerable
      interest given an increasing emphasis on making organic processes 'greener'; for
      example, by minimising organic waste in the form of organic solvents. Water is
      the obvious leading candidate in this regard. Hence, this review focuses on the
      application of micellar catalysis, in which a 'designer' surfactant enables these
      award-winning coupling reactions to be run in water at room temperature.

PMID- 23555154
TI  - MODELING REPEATED MEASURES OF DICHOTOMOUS DATA: Testing Whether the Within-Person
      Trajectory of Change Varies Across Levels of Between-Person Factors.
AB  - In this paper, we consider the following question for the analysis of data
      obtained in longitudinal panel designs: How should repeated-measures data be
      modeled and interpreted when the outcome or dependent variable is dichotomous and
      the objective is to determine whether the within-person rate of change over time
      varies across levels of one or more between-person factors? Standard approaches
      address this issue by means of generalized estimating equations or generalized
      linear mixed models with logistic links. Using an empirical example and simulated
      data, we show (1) that cross-level product terms from these models can produce
      misleading results with respect to whether the within-person rate of change
      varies across levels of a dichotomous between-person factor; and (2) that
      subgroup differences in the rate of change should be assessed on an additive
      scale (using group differences in the effects of predictors on the probability of
      disease) rather than on a multiplicative scale (using group differences in the
      effects of predictors on the odds of disease). Because usual approaches do not
      provide a significance test for whether the rate of additive change varies across
      levels of a between-person factor, sample differences in the rate of additive
      change may be due to sampling error. We illustrate how standard software can be
      used to estimate and test whether additive changes vary across levels of a
      between-person factor.

PMID- 23555155
TI  - DISCREPANCIES BETWEEN COMMUNITY VIOLENCE EXPOSURE AND PERCEIVED NEIGHBORHOOD
      VIOLENCE.
AB  - Community violence exposure (CVE) has been identified as a significant public
      health concern given its association with numerous mental health problems.
      Perceptions of neighborhood violence (PNV) also may adversely affect youth
      adjustment. In recognition that PNV may differ from individuals own experience of
      CVE, the current study utilized latent class analysis to examine the degree and
      consequences of consistency and discrepancy in adolescents community violence
      exposure and PNV. Participants included an epidemiologically-defined community
      sample of 456 African American adolescents (52% male; mean age=11.77). Results
      revealed three groups of youth: high CVE/high PNV, low CVE/low PNV, and low
      CVE/high PNV. Longitudinal analyses suggest that a discrepancy between CVE and
      PNV is important for understanding depressive and anxious symptoms among urban
      African American youth. Implications for intervention are discussed.

PMID- 23555156
TI  - Clinical features of gastroduodenal injury associated with long-term low-dose
      aspirin therapy.
AB  - Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular
      and cerebrovascular events with the advent of an aging society. On the other
      hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal
      prostaglandin levels and causes significant gastric mucosal damage. The incidence
      of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has
      been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has
      increased more than that of non-aspirin non-steroidal anti-inflammatory drug
      (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase
      (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion,
      and impaired platelet aggregation. The pathogenesis related to inhibition of COX
      2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic
      mechanisms related to direct epithelial damage are acid back diffusion and
      impaired platelet aggregation. The factors associated with an increased risk of
      upper gastrointestinal (GI) complications in subjects taking LDA are aspirin
      dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of
      non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H.
      pylori) infection. Moreover, no significant differences have been found between
      ulcer and non-ulcer groups in the frequency and severity of symptoms such as
      nausea, acid regurgitation, heartburn, and bloating. It has been shown that the
      ratios of ulcers located in the body, fundus and cardia are significantly higher
      in bleeding patients than the ratio of gastroduodenal ulcers in patients taking
      LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal
      ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated
      histamine H2-receptor antagonist is reportedly effective in prevention of LDA
      induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to
      treatment with omeprazole in preventing recurrent bleeding. Continuous aspirin
      therapy for patients with gastrointestinal bleeding may increase the risk of
      recurrent bleeding but potentially reduces the mortality rates, as stopping
      aspirin therapy is associated with higher mortality rates. It is very important
      to prevent LDA-induced gastroduodenal ulcer complications including bleeding, and
      every effort should be exercised to prevent the bleeding complications.

PMID- 23555157
TI  - Molecular mechanisms of liver ischemia reperfusion injury: insights from
      transgenic knockout models.
AB  - Ischemia reperfusion injury is a major obstacle in liver resection and liver
      transplantation surgery. Understanding the mechanisms of liver ischemia
      reperfusion injury (IRI) and developing strategies to counteract this injury will
      therefore reduce acute complications in hepatic resection and transplantation, as
      well as expanding the potential pool of usable donor grafts. The initial liver
      injury is initiated by reactive oxygen species which cause direct cellular injury
      and also activate a cascade of molecular mediators leading to microvascular
      changes, increased apoptosis and acute inflammatory changes with increased
      hepatocyte necrosis. Some adaptive pathways are activated during reperfusion that
      reduce the reperfusion injury. IRI involves a complex interplay between
      neutrophils, natural killer T-cells cells, CD4+ T cell subtypes, cytokines,
      nitric oxide synthases, haem oxygenase-1, survival kinases such as the signal
      transducer and activator of transcription, Phosphatidylinositol 3-kinases/Akt and
      nuclear factor kappabeta pathways. Transgenic animals, particularly genetic
      knockout models, have become a powerful tool at elucidating mechanisms of liver
      ischaemia reperfusion injury and are complementary to pharmacological studies.
      Targeted disruption of the protein at the genetic level is more specific and
      maintained than pharmacological inhibitors or stimulants of the same protein.
      This article reviews the evidence from knockout models of liver IRI about the
      cellular and molecular mechanisms underlying liver IRI.

PMID- 23555158
TI  - Thiopurines in inflammatory bowel disease revisited.
AB  - Although a great variety of new drugs have been introduced for the therapy of
      inflammatory bowel diseases so far, a definite cure of the disease is still out
      of scope. An anti-inflammatory approach to induce remission followed by
      maintenance therapy with immunosupressants is still the mainstay of therapy.
      Thiopurines comprising azathioprine and its active metabolite mercaptopurine as
      well as tioguanine, are widely used in the therapy of chronic active inflammatory
      bowel disease (IBD). Their steroid sparing potential and efficacy in remission
      maintenance are out of doubt. Unfortunately, untoward adverse events are
      frequently observed and may preclude further administration or be life
      threatening. This review will focus on new aspects of thiopurine therapy in IBD,
      its efficacy and safety.

PMID- 23555160
TI  - Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in
      pancreatobiliary fluids.
AB  - AIM: To evaluate the utility of measuring epigenetic alterations in pancreatic
      and biliary fluids in determining molecular markers for pancreatobiliary cancers.
      METHODS: DNA was extracted from undiluted pancreatic and biliary fluids. As a
      surrogate for a genome-wide hypomethylation assay, levels of long interspersed
      nuclear element-1 (LINE-1) methylation were analyzed using bisulfite
      pyrosequencing. CpG island hypermethylation of 10 tumor-associated genes, aryl
      hydrocarbon receptor repressor, adenomatous polyposis coli, calcium channel,
      voltage dependent, T type alpha1G subunit, insulin-like growth factor 2, O-6
      methyl-guanine-DNA methyltransferase, neurogenin 1, CDKN2A, runt-related
      transcription factor 3 (RUNX3), secreted frizzled-related protein 1, and
      ubiquitin carboxyl-terminal esterase L1 (UCHL1), was analyzed using MethyLight.
      To examine the role of CpG methylation and histone deacetylation in the silencing
      of UCHL1, human gallbladder carcinoma cell lines and pancreatic carcinoma cell
      lines were treated with 2 or 5 MUmol/L 5-AZA-dC for 72 h or 100 nmol/L
      Trichostatin A for 24 h. After the treatment, UCHL1 expression was analyzed by
      real-time reverse transcription-polymerase chain reaction. RESULTS:
      Pancreatobiliary cancers exhibited significantly lower LINE-1 methylation levels
      in pancreatic and biliary fluids than did noncancerous pancreatobiliary disease
      (58.7% +/- 4.3% vs 61.7% +/- 2.2%, P = 0.027; 53.8% +/- 6.6% vs 57.5% +/- 1.7%, P
      = 0.007); however, LINE-1 hypomethylation was more evident in pancreatic cancer
      tissues than in pancreatic fluids (45.4% +/- 5.5% vs 58.7% +/- 4.3%, P < 0.001).
      CpG island hypermethylation of tumor-associated genes was detected at various
      frequencies, but it was not correlated with LINE-1 hypomethylation.
      Hypermethylation of the UCHL1 gene was cancer-specific and most frequently
      detected in pancreatic (67%) or biliary (70%) fluids from patients with
      pancreatobiliary cancer. As a single marker, hypermethylation of the UCHL1 gene
      in pancreatic and biliary fluids was most useful for the detection of pancreatic
      and pancreatobiliary cancers, respectively (100% specificity). Hypermethylation
      of the UCHL1 and RUNX3 genes in pancreatic and biliary fluids was the most useful
      combined marker for pancreatic (87% sensitivity and 100% specificity) and
      pancreatobiliary (97% sensitivity and 100% specificity) cancers. Treatment with a
      demethylating agent, 5-AZA-2'-deoxycytidine, restored UCHL1 expression in
      pancreatobiliary cancer cell lines. CONCLUSION: Our results suggest that
      hypermethylation of UCHL1 and RUNX3 in pancreatobiliary fluid might be useful for
      the diagnosis of pancreatobiliary cancers.

PMID- 23555159
TI  - Current concepts on the role of nitric oxide in portal hypertension.
AB  - Portal hypertension (PHT) is defined as a pathological increase in portal venous
      pressure and frequently accompanies cirrhosis. Portal pressure can be increased
      by a rise in portal blood flow, an increase in vascular resistance, or the
      combination. In cirrhosis, the primary factor leading to PHT is an increase in
      intra-hepatic resistance to blood flow. Although much of this increase is a
      mechanical consequence of architectural disturbances, there is a dynamic and
      reversible component that represents up to a third of the increased vascular
      resistance in cirrhosis. Many vasoactive substances contribute to the development
      of PHT. Among these, nitric oxide (NO) is the key mediator that paradoxically
      regulates the sinusoidal (intra-hepatic) and systemic/splanchnic circulations. NO
      deficiency in the liver leads to increased intra-hepatic resistance while
      increased NO in the circulation contributes to the hyperdynamic
      systemic/splanchnic circulation. NO mediated-angiogenesis also plays a role in
      splanchnic vasodilation and collateral circulation formation. NO donors reduce
      PHT in animals models but the key clinical challenge is the development of an NO
      donor or drug delivery system that selectively targets the liver.

PMID- 23555161
TI  - Short-type single balloon enteroscope for endoscopic retrograde
      cholangiopancreatography with altered gastrointestinal anatomy.
AB  - AIM: To evaluate the effectiveness of a short-type single-balloon-enteroscope
      (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) in patients with
      a reconstructed intestine. METHODS: Short-type SBE was developed to perform ERCP
      in postoperative patients with a reconstructed intestine. Short-type SBE is a
      direct-viewing endoscope with the following specifications: working length, 1520
      mm; total length, 1840 mm; channel diameter, 3.2 mm. In addition, short-type SBE
      has a water-jet channel. The study group comprised 22 patients who underwent 31
      sessions of short-type SBE-assisted ERCP from June 2011 through May 2012.
      Reconstruction was performed by Billroth-II (B-II) gastrectomy in 6 patients (8
      sessions), Roux-en-Y (R-Y) gastrectomy in 14 patients (21 sessions), and R-Y
      hepaticojejunostomy in 2 patients (2 sessions). We retrospectively studied the
      rate of reaching the blind end (papilla of Vater or choledochojejunal
      anastomosis), mean time required to reach the blind end, diagnostic success rate
      (defined as the rate of successfully imaging the bile and pancreatic ducts),
      therapeutic success rate (defined as the rate of successfully completing
      endoscopic treatment), mean procedure time, and complications. RESULTS: Among the
      31 sessions of ERCP, the rate of reaching the blind end was 88% in B-II
      gastrectomy, 91% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The
      mean time required to reach the papilla was 18.3 min in B-II gastrectomy, 21.1
      min in R-Y gastrectomy, and 32.5 min in R-Y hepaticojejunostomy. The diagnostic
      success rates in all patients and those with an intact papilla were respectively
      86% and 86% in B-II gastrectomy, 90% and 87% in R-Y gastrectomy, and 100% in R-Y
      hepaticojejunostomy. The therapeutic success rates in all patients and those with
      an intact papilla were respectively 100% and 100% in B-II gastrectomy, 94% and
      92% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. Because the channel
      diameter was 3.2 mm, stone extraction could be performed with a wire-guided
      basket in 12 sessions, and wire-guided intraductal ultrasonography could be
      performed in 8 sessions. As for complications, hyperamylasemia (defined as a rise
      in serum amylase levels to more than 3 times the upper limit of normal) occurred
      in 1 patient (7 sessions) with a B-II gastrectomy and 4 patients (19 sessions)
      with an R-Y gastrectomy. After ERCP in patients with an R-Y gastrectomy, 2
      patients (19 sessions) had pancreatitis, 1 patient (21 sessions) had
      gastrointestinal perforation, and 1 patient (19 sessions) had papillary bleeding.
      Pancreatitis and bleeding were both mild. Gastrointestinal perforation improved
      after conservative treatment. CONCLUSION: Short-type SBE is effective for ERCP in
      patients with a reconstructed intestine and allows most conventional ERCP devices
      to be used.

PMID- 23555162
TI  - Endoplasmic reticulum stress sensitizes human esophageal cancer cell to
      radiation.
AB  - AIM: To investigate the role of endoplasmic reticulum (ER) stress in cancer
      radiotherapy and its molecular mechanism. METHODS: Tunicamycin (TM) was applied
      to induce ER stress in human esophageal cancer cell line EC109, and the
      radiosensitization effects were detected by acute cell death and clonogenic
      survival assay. Cell cycle arrest induced by TM was determined by flow cytometric
      analysis after the cellular DNA content was labeled with propidium iodide.
      Apoptosis of EC109 cells induced by TM was detected by annexin V staining and
      Western blotting of caspase-3 and its substrate poly ADP-ribose polymerase.
      Autophagic response was determined by acridine orange (AO) staining and Western
      blotting of microtubule-associated protein-1 light chain-3 (LC3) and autophagy
      related gene 5 (ATG5). In order to test the biological function of autophagy,
      specific inhibitor or Beclin-1 knockdown was used to inhibit autophagy, and its
      effect on cell apoptosis was thus detected. Additionally, involvement of the
      phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR)
      pathway was also detected by Western blotting. Finally, male nude mice inoculated
      subcutaneously with EC109 cells were used to confirm cell model observations.
      RESULTS: Our results showed that TM treatment enhanced cell death and reduced the
      colony survival fraction induced by ionizing radiation (IR), which suggested an
      obvious radiosensitization effect of TM. Moreover, TM and IR combination
      treatment led to a significant increase of G2/M phase and apoptotic cells,
      compared with IR alone. We also observed an increase of AO positive cells, and
      the protein level of LC3-II and ATG5 was induced by TM treatment, which suggested
      an autophagic response in EC109 cells. However, inhibition of autophagy by using
      a chemical inhibitor or Beclin-1 silencing led to increased cell apoptosis and
      decreased cell viability, which suggested a cytoprotective role of autophagy in
      stressed EC109 cells. Furthermore, TM treatment also activated mTORC1, and in
      turn reduced Akt phosphorylation, which suggested the PI3K/Akt/mTOR signal
      pathway was involved in the TM-induced autophagic response in EC109 cells. Tumor
      xenograft results also showed synergistic retarded tumor growth by TM treatment
      and IR, as well as the involvement of the PI3K/Akt/mTOR pathway. CONCLUSION: Our
      data showed that TM treatment sensitized human esophageal cancer cells to
      radiation via apoptosis and autophagy both in vitro and in vivo.

PMID- 23555163
TI  - Effects of hypoxia-inducible factor-1alpha silencing on the proliferation of CBRH
      7919 hepatoma cells.
AB  - AIM: To study the effects of hypoxia-inducible factor-1alpha (HIF-1alpha)
      silencing on the proliferation of hypoxic CBRH-7919 rat hepatoma cells. METHODS:
      The CBRH-7919 rat hepatoma cell line was used in this study and the hypoxic model
      was constructed using CoCl2. The HIF-1alpha-specific RNAi sequences were designed
      according to the gene coding sequence of rat HIF-1alpha obtained from GeneBank.
      The secondary structure of the HIF-1alpha gene sequence was analyzed using RNA
      draw software. The small interfering RNA (siRNA) transfection mixture was
      produced by mixing the siRNA and Lipofectamine2000(TM), and transfected into the
      hypoxic hepatoma cells. Real time reverse transcription-polymerase chain reaction
      (RT-PCR) and Western blotting assay were used to detect the expression levels of
      mRNA and protein. HIF-1alpha and vascular endothelial growth factor (VEGF) mRNA
      was determined using real time RT-PCR; the protein expression levels of AKT, p
      AKT, p21 and cyclinD1 were determined using Western blotting. The proliferation
      of hepatoma cells was observed using the methyl thiazolyl tetrazolium (MTT) assay
      and the bromodeoxyuridine (BrdU) incorporation cell proliferation assay. RESULTS:
      Under induced hypoxia, the viability of the hepatoma cells reached a minimum at
      800 MUmol/L CoCl2; the viability of the cells was relatively high at CoCl2
      concentrations between 100 MUmol/L and 200 MUmol/L. Under hypoxia, the mRNA and
      protein expression levels of HIF-1alpha and VEGF were significantly higher than
      that of hepatoma cells that were cultured in normaxia. HIF-1alpha-specific RNAi
      sequences were successfully transfected into hepatoma cells. The transfection of
      specific siRNAs significantly inhibited the mRNA and protein expression levels of
      HIF-1alpha and VEGF, along with the protein expression levels of p-AKT and
      cyclinD1; the protein expression of p21 was significantly increased, and there
      was no significant difference in the expression of AKT. The MTT assay showed that
      the amount of hepatoma cells in S phase in the siRNA transfection group was
      obviously smaller than that in the control group; in the siRNA transfection
      group, the amount of hepatoma cells in G1 phase was more than that in the control
      group. The BrdU incorporation assay showed that the number of BrdU positive
      hepatoma cells in the siRNA transfection group was less than that in the control
      group. The data of the MTT assay and BrdU incorporation assay suggested that HIF
      1alpha silencing using siRNAs significantly inhibited the proliferation of
      hepatoma cells. CONCLUSION: Hypoxia increases the expression of HIF-1alpha, and
      HIF-1alpha silencing significantly inhibits the proliferation of hypoxic CBRH
      7919 rat hepatoma cells.

PMID- 23555164
TI  - Effects of small interfering RNA inhibit Class I phosphoinositide 3-kinase on
      human gastric cancer cells.
AB  - AIM: To investigate the effects of small interfering RNA (siRNA)-mediated
      inhibition of Class I phosphoinositide 3-kinase (Class I PI3K) signal
      transduction on the proliferation, apoptosis, and autophagy of gastric cancer
      SGC7901 and MGC803 cells. METHODS: We constructed the recombinant replication
      adenovirus PI3K(I)-RNA interference (RNAi)-green fluorescent protein (GFP) and
      control adenovirus NC-RNAi-GFP, and infected it into human gastric cancer cells.
      MTT assay was used to determine the growth rate of the gastric cancer cells.
      Activation of autophagy was monitored with monodansylcadaverine (MDC) staining
      after adenovirus PI3K(I)-RNAi-GFP and control adenovirus NC-RNAi-GFP treatment.
      Immunofluorescence staining was used to detect the expression of microtubule
      associated protein 1 light chain 3 (LC3). Mitochondrial membrane potential was
      measured using the fluorescent probe JC-1. The expression of autophagy was
      monitored with MDC, LC3 staining, and transmission electron microscopy. Western
      blotting was used to detect p53, Beclin-1, Bcl-2, and LC3 protein expression in
      the culture supernatant. RESULTS: The viability of gastric cancer cells was
      inhibited after siRNA targeting to the Class I PI3K blocked Class I PI3K signal
      pathway. MTT assays revealed that, after SGC7901 cancer cells were treated with
      adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 27.48% +/- 2.71% at
      24 h, 41.92% +/- 2.02% at 48 h, and 50.85% +/- 0.91% at 72 h. After MGC803 cancer
      cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition
      reached 24.39% +/- 0.93% at 24 h, 47.00% +/- 0.87% at 48 h, and 70.30% +/- 0.86%
      at 72 h (P < 0.05 compared to control group). It was determined that when 50 MOI,
      the transfection efficiency was 95% +/- 2.4%. Adenovirus PI3K(I)-RNAi-GFP (50
      MOI) induced mitochondrial dysfunction and activated cell apoptosis in SGC7901
      cells, and the results described here prove that RNAi of Class I PI3K induced
      apoptosis in SGC7901 cells. The results showed that adenovirus PI3K(I)-RNAi-GFP
      transfection induced punctate distribution of LC3 immunoreactivity, indicating
      increased formation of autophagosomes. The results showed that the basal level of
      Beclin-1 and LC3 protein in SGC7901 cells was low. After incubating with
      adenovirus PI3K(I)-RNAi-GFP (50 MOI), Beclin-1, LC3, and p53 protein expression
      was significantly increased from 24 to 72 h. We also found that Bcl-2 protein
      expression down-regulated with the treatment of adenovirus PI3K(I)-RNAi-GFP (50
      MOI). A number of isolated membranes, possibly derived from ribosome-free
      endoplasmic reticulum, were seen. These isolated membranes were elongated and
      curved to engulf a cytoplasmic fraction and organelles. We used transmission
      electron microscopy to identify ultrastructural changes in SGC7901 cells after
      adenovirus PI3K(I)-RNAi-GFP (50 MOI) treatment. Control cells showed a round
      shape and contained normal-looking organelles, nucleus, and chromatin, while
      adenovirus PI3K(I)-RNAi-GFP (50 MOI)-treated cells exhibited the typical signs of
      autophagy. CONCLUSION: After the Class I PI3K signaling pathway has been blocked
      by siRNA, the proliferation of cells was inhibited and the apoptosis of gastric
      cancer cells was enhanced.

PMID- 23555165
TI  - Psychosocial factors and their association with reflux oesophagitis, Barrett's
      oesophagus and oesophageal adenocarcinoma.
AB  - AIM: To investigate the role of psychological characteristics as risk factors for
      oesophageal adenocarcinoma (OAC), as well as the reflux-mediated precursor
      pathway. METHODS: An all-Ireland population-based case-control study recruited
      230 reflux oesophagitis (RO), 224 Barrett's oesophagus (BO) and 227 OAC patients
      and 260 controls. Each case/control group completed measures of stress,
      depression, self-efficacy, self-esteem, repression and social support. A
      comparative analysis was undertaken using polytomous logistic regression adjusted
      for potential confounders. RESULTS: Compared to controls, OAC patients were
      almost half as likely to report high stress levels over their lifetime (P =
      0.010, OR 0.51; 95%CI: 0.29-0.90) and 36% less likely to report having
      experienced depression (OR 0.64; 95%CI: 0.42-0.98). RO patients reported
      significantly higher stress than controls particularly during middle- and senior
      years (P for trends < 0.001). RO patients were 37% less likely to report having
      been highly emotionally repressed (OR 0.63; 95%CI: 0.41-0.95). All case groups
      (OAC, RO and BO) were more likely than controls to report having had substantial
      amounts of social support (OR 2.84; 95%CI: 1.63-4.97; OR 1.97; 95%CI: 1.13-3.44
      and OR 1.83; 95%CI: 1.03-3.24, respectively). CONCLUSION: The improved
      psychological profile of OAC patients may be explained by response shift. The
      role of psychological factors in the development of OAC requires further
      investigation.

PMID- 23555166
TI  - Evaluation of the relationship between dietary factors, CagA-positive
      Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric
      cancer tissue.
AB  - AIM: To evaluate the relationship among Helicobacter pylori (H. pylori)
      infection, CagA status, and dietary factors with RUNX3 promoter hypermethylation.
      METHODS: Gastric cancer tissue samples were collected from 184 South Korean
      patients. All patients were interviewed following a semi-quantitative food
      frequency questionnaire. The average frequencies of intake and portion sizes of
      89 common food items were documented, and total intakes of calories, nutrients,
      vitamins, and minerals were calculated for each subject. DNA was extracted from
      gastric cancer tissue samples, and amplification of the HSP60 gene was performed
      to detect H. pylori infection. Nested polymerase chain reaction (PCR) was used to
      detect the presence of the CagA gene. RUNX3 gene expression was measured by
      reverse transcription-PCR, and RUNX3 methylation status was evaluated by
      methylation-specific PCR. The odds ratios (ORs) and 95%CI associated with RUNX3
      promoter hypermethylation status were estimated for each of the food groups,
      lifestyle factors, and the interaction between dietary and lifestyle factors with
      CagA status of H. pylori infection. RESULTS: Overall, 164 patients (89.1%) were
      positive for H. pylori DNA, with the CagA gene detected in 59 (36%) of these H.
      pylori-positive samples. In all, 106 (57.6%) patients with gastric cancer
      demonstrated CpG island hypermethylation at the RUNX3 promoter. RUNX3 expression
      was undetectable in 52 (43.7%) of the 119 gastric cancer tissues sampled. A high
      consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer
      patients, having a mean OR of 2.15 (range, 1.14-4.08). A significantly increased
      OR of 4.28 (range, 1.19-15.49) was observed with a high consumption of nuts in
      patients with CagA-positive H. pylori infection. High intakes of carbohydrate,
      vitamin B1, and vitamin E may decrease the risk of RUNX3 methylation in gastric
      cancer tissue, particularly in CagA- or H. pylori-negative infection, with OR of
      0.41 (0.19-0.90), 0.42 (0.20-0.89), and 0.29 (0.13-0.62), respectively. A high
      consumption of fruits may protect against RUNX3 methylation. CONCLUSION: These
      results suggest that the CagA status of H. pylori infection may be a modifier of
      dietary effects on RUNX3 methylation in gastric cancer tissue.

PMID- 23555167
TI  - Common bile duct stones on multidetector computed tomography: attenuation
      patterns and detectability.
AB  - AIM: To investigate the attenuation patterns and detectability of common bile
      duct (CBD) stones by multidetector computed tomography (MDCT). METHODS: Between
      March 2010 and February 2012, 191 patients with suspicion of CBD stones
      undergoing both MDCT and endoscopic retrograde cholangiopancreatography (ERCP)
      were enrolled and reviewed retrospectively. The attenuation patterns of CBD
      stones on MDCT were classified as heavily calcified, radiopaque, less radiopaque,
      or undetectable. The association between the attenuation patterns of CBD stones
      on MDCT and stone type consisting of pure cholesterol, mixed cholesterol, brown
      pigment, and black pigment and the factors related to the detectability of CBD
      stones by MDCT were evaluated. RESULTS: MDCT showed CBD stones in 111 of 130
      patients in whom the CBD stones were demonstrated by ERCP with 85.4% sensitivity.
      The attenuation patterns of CBD stones on MDCT were heavily calcified 34 (26%),
      radiopaque 31 (24%), less radiopaque 46 (35%), and undetectable 19 (15%). The
      radiopacity of CBD stones differed significantly according to stone type (P <
      0.001). From the receiver operating characteristic curve, stone size was useful
      for the determination of CBD stone by MDCT (area under curve 0.779, P < 0.001)
      and appropriate cut-off stone size on MDCT was 5 mm. The factors related to
      detectability of CBD stones on MDCT were age, stone type, and stone size on
      multivariate analysis (P < 0.05). CONCLUSION: The radiopacity of CBD stones on
      MDCT differed according to stone type. Stone type and stone size were related to
      the detectability by MDCT, and appropriate cut-off stone size was 5 mm.

PMID- 23555168
TI  - Routine defunctioning stoma after chemoradiation and total mesorectal excision: a
      single-surgeon experience.
AB  - AIM: To investigate the 10-year results of treating low rectal cancer by a single
      surgeon in one institution. METHODS: From Oct 1998 to Feb 2009, we prospectively
      followed a total of 62 patients with cT2-4 low rectal cancer with lower tumor
      margins measuring at 3 to 6 cm above the anal verge. All patients received
      neoadjuvant chemoradiation (CRT) for 6 wk. Among them, 85% of the patients
      received 225 mg/m(2)/d 5-fluorouracil using a portable infusion pump. The whole
      pelvis received a total dose of 45 Gy of irradiation in 25 fractions over 5 wk.
      The interval from CRT completion to surgical intervention was planned to be
      approximately 6-8 wk. Total mesorectal excision (TME) and routine defunctioning
      stoma construction were performed by one surgeon. The distal resection margin,
      circumferential resection margin, tumor regression grade (TRG) and other
      parameters were recorded. We used TRG to evaluate the tumor response after
      neoadjuvant CRT. We evaluated anal function outcomes using the Memorial Sloan
      Kettering Cancer Center anal function scores after closure of the defunctioning
      stoma. RESULTS: The median distance from the lower margin of rectal cancer to the
      anal verge was 5 cm: 6 cm in 9 patients, 5 cm in 32 patients, 4 cm in 10
      patients, and 3 cm in 11 patients. Before receiving neoadjuvant CRT, 45 patients
      (72.6%) had a cT3-4 tumor, and 21 (33.9%) patients had a cN1-2 lymph node status.
      After CRT, 30 patients (48.4%) had a greater than 50% clinical reduction in tumor
      size. The final pathology reports revealed that 33 patients (53.2%) had a ypT3-4
      tumor and 12 (19.4%) patients had ypN1-2 lymph node involvement. All patients
      completed the entire course of neoadjuvant CRT. Most patients developed only
      Grade 1-2 toxicities during CRT. Thirteen patients (21%) achieved a pathologic
      complete response. Few post-operative complications occurred. Nearly 90% of the
      defunctioning stomas were closed within 6 mo. The local recurrence rate was 3.2%.
      Pathologic lymph node involvement was the only prognostic factor predicting
      disease recurrence (36.5% vs 76.5%, P = 0.006). Nearly 90% of patients recovered
      sphincter function within 2 year after closure of the defunctioning stoma.
      CONCLUSION: Neoadjuvant CRT followed by TME, combined with routine defunctioning
      stoma construction and high-volume surgeon experience, can provide excellent
      surgical quality and good local disease control.

PMID- 23555169
TI  - Esophagogastroduodenoscopy with conscious sedation does not interfere with
      catheter-based 24-h pH monitoring.
AB  - AIM: To investigate the impact of esophagogastroduodenoscopy with conscious
      sedation on the subsequent 24-h catheter-based pH monitoring. METHODS: Fifty
      patients with extra-esophageal symptoms of gastroesophageal reflux disease
      undergoing ambulatory dual-probe 24-h pH monitoring were enrolled from March 2010
      to August 2011. All of the data were collected prospectively and analyzed
      retrospectively. Thirty-six patients (72%, group A) underwent pH monitoring
      shortly after esophagogastroduodenoscopy (EGD) with conscious sedation, and 14
      patients (28%, group B) underwent pH monitoring without conscious sedation. The
      24-h pH data from two time periods were analyzed: the first 4 h (Period I) and
      the remaining time of the study (Period II). RESULTS: The mean age of the
      patients was 49.6 +/- 12.5 years; 20 patients (40%) were men. The baseline data,
      including age, sex, body mass index, reflux esophagitis, the Reflux Symptom
      Index, and the Reflux Findings Score, were comparable between the two groups. The
      percentage of total time with a pH < 4 and the frequency of acid reflux during
      Period I were not significantly different between the two groups, as measured
      using both pharyngeal (0.03% +/- 0.10% vs 0.07% +/- 0.16%, P = 0.32; and 0.07 +/-
      0.23 episodes/h vs 0.18 +/- 0.47 episodes/h, P = 0.33, respectively) and
      esophageal probes (0.96% +/- 1.89% vs 0.42% +/- 0.81%, P = 0.59; and 0.74 +/-
      1.51 episodes/h vs 0.63 +/- 0.97 episodes/h, P = 0.49, respectively). The
      percentage of total time with a pH < 4 and the frequency of acid reflux were also
      not significantly different between Periods I and II in group A patients, as
      measured using both pharyngeal (0.03% +/- 0.10% vs 0.23% +/- 0.85%, P = 0.21; and
      0.07 +/- 0.23 episodes/h vs 0.29 +/- 0.98 episodes/h, P = 0.22, respectively) and
      esophageal probes (0.96% +/- 1.89% vs 1.11% +/- 2.57%, P = 0.55; and 0.74 +/-
      1.51 episodes/h vs 0.81 +/- 1.76 episodes/h, P = 0.55, respectively). CONCLUSION:
      EGD with conscious sedation does not interfere with the results of subsequent 24
      h pH monitoring in patients with extra-esophageal symptoms of gastroesophageal
      reflux disease.

PMID- 23555170
TI  - Value of alpha-fetoprotein in association with clinicopathological features of
      hepatocellular carcinoma.
AB  - AIM: To explore the relationship between alpha-fetoprotein (AFP) and various
      clinicopathological variables and different staging system of hepatocellular
      carcinoma (HCC) thoroughly. METHODS: A retrospective cohort study of consecutive
      patients diagnosed with HCC between January 2008 and December 2009 in West China
      Hospital was enrolled in our study. The association of serum AFP values with the
      HCC clinicopathological features was analysed by univariate and multivariate
      analysis, such as status of hepatitis B virus (HBV) infection, tumor size, tumor
      number, vascular invasion and degree of tumor differentiation. Also, patients
      were divided into four groups at the time of enrollment according to different
      cutoff values for serum value of AFP (<= 20 MUg/L, 21-400 MUg/L, 401-800 MUg/L,
      and >= 801 MUg/L), to compare the positive rate of patient among four groups
      stratified by various clinicopathological variables. And the correlation of
      different kinds of tumor staging systems, such as TNM, Barcelona Clinic Liver
      Cancer (BCLC) staging classification and China staging, were compared with the
      serum concentration of AFP. RESULTS: A total of 2304 HCC patients were enrolled
      in this study totally; the mean serum level of AFP was 555.3 +/- 546.6 MUg/L. AFP
      levels were within the normal range (< 20 MUg/L) in 27.4% (n = 631) of all the
      cases. 81.4% (n = 1875) patients were infected with HBV, and those patients had
      much higher serum AFP level compared with non-HBV infection ones (573.9 +/- 547.7
      MUg/L vs 398.4 +/- 522.3 MUg/L, P < 0.001). The AFP level in tumors >= 10 cm
      (808.4 +/- 529.2 MUg/L) was significantly higher (P < 0.001) than those with
      tumor size 5-10 cm (499.5 +/- 536.4 MUg/L) and with tumor size <= 5 cm (444.9 +/-
      514.2 MUg/L). AFP levels increased significantly in patients with vascular
      invasion (694.1 +/- 546.9 MUg/L vs 502.1 +/- 543.1 MUg/L, P < 0.001). Patients
      with low tumor cell differentiation (559.2 +/- 545.7 MUg/L) had the significantly
      (P = 0.007) highest AFP level compared with high differentiation (207.3 +/- 420.8
      MUg/L) and intermediate differentiation (527.9 +/- 538.4 MUg/L). In the multiple
      variables analysis, low tumor cell differentiation [OR 6.362, 95%CI: 2.891
      15.382, P = 0.006] and tumor size (>= 10 cm) (OR 5.215, 95%CI: 1.426-13.151, P =
      0.012) were independent predictors of elevated AFP concentrations (AFP > 400
      MUg/L). Serum AFP levels differed significantly (P < 0.001) in the D stage of
      BCLC (625.7 +/- 529.8 MUg/L) compared with stage A (506.2 +/- 537.4 MUg/L) and B
      (590.1 +/- 551.1 MUg/L). CONCLUSION: HCC differentiation, size and vascular
      invasion have strong relationships with AFP, poor differentiation and HCC size >=
      10 cm are independent predictors of elevated AFP. BCLC shows better relationship
      with AFP.

PMID- 23555171
TI  - Double-balloon enteroscopy for mesenchymal tumors of small bowel: nine years'
      experience.
AB  - AIM: To assess the value of double-balloon enteroscopy (DBE) for the diagnosis of
      gastrointestinal mesenchymal tumors (GIMTs) in the small bowel and clarify their
      clinical and endoscopic characteristics. METHODS: A retrospective review in a
      total of 783 patients who underwent a DBE procedure from January 2003 to December
      2011 was conducted. Data from patients with pathologically confirmed GIMTs were
      analyzed at a single tertiary center with nine years' experience. The primary
      outcomes assessed included characteristics of patients with GIMTs, indications
      for DBE, overall diagnostic yield of GIMTs, endoscopic morphology, positive
      biopsy, comparison of diagnosis with capsule endoscopy, and subsequent
      interventional management. RESULTS: GIMTs were identified and analyzed in 77
      patients. The mean age was 47.74 +/- 14.14 years (range: 20-77 years), with 63.6%
      being males. The majority of individuals presented with gastrointestinal
      bleeding, accounting for 81.8%, followed by abdominal pain, accounting for 10.4%.
      Small bowel pathologies were found in 71 patients, the detection rate was 92.2%.
      The diagnostic yield of DBE for GIMTs was 88.3%. DBE was superior to capsule
      endoscopy in the diagnosis of GIMTs (P = 0.006; McNemar's chi(2) test).
      Gastrointestinal stromal tumor was the most frequent and leiomyoma was the second
      frequent GIMT. Single and focal lesions were typical of GIMTs, and masses with
      smooth or unsmooth surface were the most common in the small bowel. GIMTs were
      removed from all the patients surgically except one patient treated with
      endoscopic resection. CONCLUSION: DBE is a safe and valuable procedure for
      patients with suspected GIMTs, and it provides an accurate position for
      subsequent surgical intervention.

PMID- 23555172
TI  - Multicenter case-control study of the risk factors for ulcerative colitis in
      China.
AB  - AIM: To evaluate potential risk factors in the development of ulcerative colitis
      (UC) in China. METHODS: A total of 1308 patients with UC and 1308 age-matched and
      sex-matched controls were prospectively studied in China. The UC cases were
      collected from 17 hospitals in China from April 2007 to April 2010. Uniform
      questionnaires were designed to investigate risk factors including smoking,
      appendectomy, stress, socio-economic conditions, nonsteroidal anti-inflammatory
      drugs (NSAIDs), oral contraceptives, diet, breastfeeding, infections and family
      sanitary conditions. Group comparisons by each factor were done using simple
      logistic regression analysis. Conditional logistic regression was used for
      multivariate analysis. RESULTS: By univariate analysis, the variables predictive
      of UC included feeling stress, light and heavy alcoholic drinking, spicy food,
      sugar consumption and infectious diarrhea, while heavy tea intake and tap water
      consumption were protective against UC. On multivariate analysis, the protective
      factor for UC was tap water consumption [odds ratios (OR) = 0.424, 95%CI: 0.302
      0.594, P < 0.001]; while the potential risk factors for UC were heavy sugar
      consumption (OR = 1.632, 95%CI: 1.156-2.305, P < 0.001), spicy food (light
      intake: OR = 3.329, 95%CI: 2.282-4.857, P < 0.001; heavy intake: OR = 3.979,
      95%CI: 2.700-5.863, P < 0.001), and often feeling stress (OR = 1.981, 95%CI:
      1.447-2.711, P < 0.001). Other factors, such as smoking habit, appendectomy,
      breastfeeding, a history of measles, rural or urban residence, education, oral
      contraceptives, and NSAID use have not been found to have a significant
      association with the development of UC in the present study. CONCLUSION: Our
      study showed tap water consumption was a protective factor for UC, while spicy
      food, heavy sugar consumption and often feeling stress were risk factors for UC
      in this Chinese population.

PMID- 23555173
TI  - Case of autoimmune hepatitis with markedly enlarged hepatoduodenal ligament lymph
      nodes.
AB  - Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown
      etiology. The disease is characterized histologically by interface hepatitis,
      biochemically by increased aspartate aminotransferase and alanine
      aminotransferase levels, and serologically by increased autoantibodies and
      immunoglobulin G levels. Here we discuss AIH in a previously healthy 37-year-old
      male with highly elevated serum levels of soluble interleukin-2 receptor and
      markedly enlarged hepatoduodenal ligament lymph nodes (HLLNs, diameter, 50 mm).
      Based on these observations, the differential diagnoses were AIH, lymphoma, or
      Castleman's disease. Liver biopsy revealed the features of interface hepatitis
      without bridging fibrosis along with plasma cell infiltration which is the
      typical characteristics of acute AIH. Lymph node biopsy revealed lymphoid
      follicles with inflammatory lymphocytic infiltration; immunohistochemical
      examination excluded the presence of lymphoma cells. Thereafter, he was
      administered corticosteroid therapy: after 2 mo, the enlarged liver reached an
      almost normal size and the enlarged HLLNs reduced in size. We could not find AIH
      cases with such enlarged lymph nodes (diameter, 50 mm) in our literature review.
      Hence, we speculate that markedly enlarged lymph nodes observed in our patient
      may be caused by a highly activated, humoral immune response in AIH.

PMID- 23555174
TI  - A case of colon perforation due to enteropathy-associated T-cell lymphoma.
AB  - Enteropathy-associated T-cell lymphoma (EATL) is an extremely rare disease, which
      is often related to gluten-sensitive enteropathy. It is an uncommon intestinal
      lymphoma with very poor prognosis and high mortality rate. In the absence of
      specific symptoms or radiological findings, it is difficult to diagnose early.
      Major complications of EATL have been known as intestinal perforation or
      obstruction, and only 5 cases of EATL are reported in South Korea. In this study,
      we report a case of 71-year-old male with symptoms of diarrhea, which later it
      progressed into cancer perforation of the colon. The initial colonoscopic
      findings were normal and computed tomography scan demonstrated a segmental wall
      thickening of the distal ascending colon with nonspecific multiple small
      lymphnodes, along the ileocolic vessels, but no signs of mass or obstruction. The
      histologic findings of resected specimen confirmed EATL type II. Patient expired
      two weeks after the operation. Therefore, we emphasize the need of random biopsy
      in the presence of normal mucosa appearance on colonoscopy for the early
      diagnosis of EATL.

PMID- 23555175
TI  - Muco-submucosal elongated polyps of the gastrointestinal tract: a case series and
      a review of the literature.
AB  - We present three cases of gastrointestinal muco-submucosal elongated polyps, two
      located in the duodenum and one in the descending colon. All three cases had a
      characteristic, "worm-like" endoscopic appearance and were lined by unremarkable
      mucosa. The vascular component was located in the submucosa and was composed of a
      mixture of variably dilated blood vessels (capillaries and veins) and lymphatics.
      The duodenal polyps displayed lipomatous metaplasia of the submucosal stroma. The
      dual vascular phenotype of the vascular component was confirmed by
      immunohistochemistry with D2-40 and CD31.

PMID- 23555176
TI  - Synchronous adenocarcinoma and extranodal natural killer/T-cell lymphoma of the
      colon: a case report and literature review.
AB  - Extranodal natural killer/T-cell lymphoma (ENKTL) is a distinct subtype of non
      Hodgkin's lymphoma and is rare in the colon. Synchronous adenocarcinoma and ENKTL
      of the colon has not been reported in the literature. In the present study, we
      report a 63-year-old male who suffered from intermittent bloody stools for 2 mo.
      He did not have fever, body weight loss or night sweat. Endoscopic and imaging
      studies revealed a 4.5-cm ulcerative mass in the ascending colon and a 3.0-cm
      polypoid, easy bleeding mass in the sigmoid colon, respectively. Thought to have
      double carcinoma of the colon, he received simultaneous right hemicolectomy and
      sigmoidectomy. The pathological diagnosis was a synchronous ENKTL (ascending
      colon) and adenocarcinoma (sigmoid colon). The literature on synchronous
      adenocarcinoma and malignant lymphoma of the colon was also reviewed.

PMID- 23555178
TI  - Echocardiographic estimation of pulmonary capillary wedge pressure using the
      combination of diastolic annular and mitral inflow velocities.
AB  - BACKGROUND: We aimed to identify the clinical utility of a simple
      echocardiographic approach for estimating the pulmonary capillary wedge pressure
      (PCWP) on the basis of the combined assessment of mitral inflow and tissue
      Doppler mitral annular velocities. METHODS: We retrospectively enrolled 165
      patients who underwent both echocardiographic examination and right heart
      catheterization, and determined the diagnostic accuracy of echocardiography
      derived parameters for estimating PCWP >18 mmHg. RESULTS: Eighty-three patients
      had preserved left ventricular (LV) ejection fraction >=50% (the PEF group) and
      82 patients had reduced LVEF <50% (the REF group). The PEF group had higher peak
      early mitral annular velocity (E') compared with the REF group. Eight patients in
      the PEF group but none in the REF group had normal LV diastolic function,
      represented as E' >8 cm/s, and all of these patients had normal inflow pattern.
      The mean PCWP had the strongest correlation with the ratio of the peak early
      mitral inflow velocity (E) to the peak late diastolic mitral inflow velocity
      during atrial contraction (E/A) in both groups, followed by the left atrial
      diameter and E/E' in both patient groups. Receiver operating characteristic (ROC)
      analysis demonstrated that the combination of abnormal E' <=8 and elevated E/A
      had high diagnostic accuracy compared with E/E' in both patient groups with
      different cutoff values of E/A (1.81 in the PEF group and 1.16 in the REF group)
      for predicting mean PCWP >18 mmHg. CONCLUSION: After excluding patients with
      normal diastolic function using E', conventional E/A is a reliable marker for
      predicting high PCWP and is superior to E/E'.

PMID- 23555179
TI  - Detailed modelling of delamination buckling of thin films under global tension.
AB  - Tensile specimens of metal films on compliant substrates are widely used for
      determining interfacial properties. These properties are identified by the
      comparison of experimentally observed delamination buckling and a mathematical
      model which contains the interface properties as parameters. The current two
      dimensional models for delamination buckling are not able to capture the complex
      stress and deformation states arising in the considered uniaxial tension test in
      a satisfying way. Therefore, three-dimensional models are developed in a multi
      scale approach. It is shown that, for the considered uniaxial tension test, the
      buckling and associated delamination process are initiated and driven by
      interfacial shear in addition to compressive stresses in the film. The proposed
      model is able to reproduce all important experimentally observed phenomena, like
      cracking stress of the film, film strip curvature and formation of triangular
      buckles. Combined with experimental data, the developed computational model is
      found to be effective in determining interface strength properties.

PMID- 23555177
TI  - Do men's faces really signal heritable immunocompetence?
AB  - In the literature on human mate choice, masculine facial morphology is often
      proposed to be an intersexual signal of heritable immunocompetence, and hence an
      important component of men's attractiveness. This hypothesis has received
      considerable research attention, and is increasingly treated as plausible and
      well supported. In this article, we propose that the strength of the evidence for
      the immunocompetence hypothesis is somewhat overstated, and that a number of
      difficulties have been under-acknowledged. Such difficulties include (1) the
      tentative nature of the evidence regarding masculinity and disease in humans, (2)
      the complex and uncertain picture emerging from the animal literature on sexual
      ornaments and immunity, (3) the absence of consistent, cross-cultural support for
      the predictions of the immunocompetence hypothesis regarding preferences for
      masculinized stimuli, and (4) evidence that facial masculinity contributes very
      little, if anything, to overall attractiveness in real men. Furthermore,
      alternative explanations for patterns of preferences, in particular the proposal
      that masculinity is primarily an intrasexual signal, have been neglected. We
      suggest that immunocompetence perspectives on masculinity, whilst appealing in
      many ways, should still be regarded as speculative, and that other perspectives
      and other traits-should be the subject of greater attention for researchers
      studying human mate preferences.

PMID- 23555180
TI  - Synthesis and Characterization of Germanium Coordination Compounds for Production
      of Germanium Nanomaterials.
AB  - A series of novel germanium(II) precursors was synthesized to initiate an
      investigation between the precursors' structures and the morphologies of the
      resulting nanoparticles. The precursors were synthesized from the reaction of
      Ge[N(SiMe3)2]2 or [Ge(OBut)2]2 and the appropriate ligand: N,N'
      dibenzylethylenediamine (H2-DBED), tert-butanol (H-OBut), 2,6-di-methyl phenol (H
      DMP), 2,6-di-phenyl phenol (H-DPP), tert-butyldimethylsilanol (H-DMBS),
      triphenylsilanol (H-TPS), triphenylsilanethiol (H-TPST), and benzenethiol (H-PS).
      The products were identified as: [Ge(MUc-DBED)]2 (1, MUc= bridging chelating),
      [Ge(MU-DMP)(DMP)]2 (2), Ge(DPP)2 (3), [Ge(MU-OBut)(DMBS)]2, (4), [Ge(MU
      DMBS)(DMBS)]2 (5), Ge(TPS)3(H) (6), [Ge(MU-TPST)(TPST)]2 (7), and Ge(PS)4 (8).
      The Ge(II) metal centers were found to adopt a pyramidal geometry for 1, 2, 4, 5,
      7, a bent arrangement for 3, and a tetrahedral coordination for the Ge(IV)
      species 6 and 8. Using a simple solution precipitation methodology, Ge(0)
      nanomaterials were isolated as dots and wires for the majority of precursors.
      Compound 7 led to the isolation of amorphous GexSy. The nanomaterials isolated
      were characterized by TEM, EDS, and powder XRD. A correlation between the
      precursor's arrangement and final observed nanomorphology was proffered as part
      of the 'precursor structure affect' phenomenon.

PMID- 23555181
TI  - Targeting inhibition of fibroblast activation protein-alpha and prolyl
      oligopeptidase activities on cells common to metastatic tumor microenvironments.
AB  - Fibroblast activation protein (FAP), a membrane prolyl-specific proteinase with
      both dipeptidase and endopeptidase activities, is overexpressed by reactive
      stromal fibroblasts during epithelial-derived cancer growth. FAP digests
      extracellular matrix as tissue is remodeled during cancer expansion and may also
      promote an immunotolerant tumor microenvironment. Recent studies suggest that
      nonspecific FAP inhibitors suppress human cancer xenografts in mouse models.
      Prolyl oligopeptidase (POP), another prolyl-specific serine proteinase, is also
      elevated in many cancers and may have a regulatory role in angiogenesis
      promotion. FAP and POP cell-associated activities may be targets for diagnosis
      and treatment of various cancers, but their accessibilities to highly effective
      specific inhibitors have not been shown for cells important to cancer growth.
      Despite their frequent simultaneous expression in many cancers and their
      overlapping activities toward commonly used substrates, precise, separate
      measurement of FAP or POP activity has largely been ignored. To distinguish each
      of the two activities, we synthesized highly specific substrates and inhibitors
      for FAP or POP based on amino acid sequences surrounding the scissile bonds of
      their respective putative substrates. We found varying amounts of FAP and POP
      protein and activities on activated fibroblasts, mesenchymal cells, normal breast
      cells, and one breast cancer cell line, with some cells exhibiting more POP than
      FAP activity. Replicating endothelial cells (ECs) expressed POP but not FAP until
      tubulogenesis began. Targeting FAP-positive cells, especially mesenchymal stem
      cells and cancer-associated fibroblasts for inactivation or destruction, and
      inhibiting POP-producing EC may abrogate stromal invasion and angiogenesis
      simultaneously and thereby diminish cancer growth.

PMID- 23555182
TI  - ERK2-regulated TIMP1 induces hyperproliferation of K-Ras(G12D)-transformed
      pancreatic ductal cells.
AB  - Pancreatic ductal adenocarcinoma (PDAC) commonly contains a mutation in K
      Ras(G12D) and is characterized by a desmoplastic reaction composed of
      deregulated, proliferating cells embedded in an abnormal extracellular matrix
      (ECM). Our previous observations imply that inhibiting the mitogen-activated
      protein kinase (MAPK)-extracellular signal-regulated kinase (ERK2) kinase signal
      pathway reverses a matrix metalloproteinase 1-specific invasive phenotype. Here,
      we investigated the specific genes downstream of MAPK-ERK2 responsible for the
      hyperproliferative abilities of human and murine primary ductal epithelial cells
      (PDCs) within an ECM. Compared with control, DNA synthesis and total cell
      proliferation was significantly increased in human PDCs harboring the PDAC common
      p53, Rb/p16(INK4a), and K-Ras (G12D) mutations. Both of these effects were
      readily reversed following small-molecule inhibition or lentiviral silencing of
      ERK2. Microarray analysis of PDCs in three-dimensional (3D) culture revealed a
      unique, MAPK-influenced gene signature downstream of K-Ras (G12D). Unbiased
      hierarchical analysis permitted filtration of tissue inhibitor of matrix
      metalloproteinase 1 (TIMP1). Pancreatic cells isolated from Pdx1-Cre; LSL-K
      ras(G12D/+)-mutated mice exhibit increased TIMP1 RNA transcription compared to
      wild-type littermate controls. Analyses of both 3D, in vitro human K-Ras (G12D)
      PDCs and data mining of publicly annotated human pancreatic data sets
      correlatively indicate increased levels of TIMP1 RNA. While silencing TIMP1 did
      not significantly effect PDC proliferation, exogenous addition of human
      recombinant TIMP1 significantly increased proliferation but only in transformed K
      Ras (G12D) PDCs in 3D. Overall, TIMP1 is an upregulated gene product and a
      proliferative inducer of K-Ras(G12D)-mutated PDCs through the ERK2 signaling
      pathway.

PMID- 23555183
TI  - Epigenomic alterations in localized and advanced prostate cancer.
AB  - Although prostate cancer (PCa) is the second leading cause of cancer death among
      men worldwide, not all men diagnosed with PCa will die from the disease. A
      critical challenge, therefore, is to distinguish indolent PCa from more advanced
      forms to guide appropriate treatment decisions. We used Enhanced Reduced
      Representation Bisulfite Sequencing, a genome-wide high-coverage single-base
      resolution DNA methylation method to profile seven localized PCa samples, seven
      matched benign prostate tissues, and six aggressive castration-resistant prostate
      cancer (CRPC) samples. We integrated these data with RNA-seq and whole-genome DNA
      seq data to comprehensively characterize the PCa methylome, detect changes
      associated with disease progression, and identify novel candidate prognostic
      biomarkers. Our analyses revealed the correlation of cytosine guanine
      dinucleotide island (CGI)-specific hypermethylation with disease severity and
      association of certain breakpoints (deletion, tandem duplications, and
      interchromosomal translocations) with DNA methylation. Furthermore, integrative
      analysis of methylation and single-nucleotide polymorphisms (SNPs) uncovered
      widespread allele-specific methylation (ASM) for the first time in PCa. We found
      that most DNA methylation changes occurred in the context of ASM, suggesting that
      variations in tumor epigenetic landscape of individuals are partly mediated by
      genetic differences, which may affect PCa disease progression. We further
      selected a panel of 13 CGIs demonstrating increased DNA methylation with disease
      progression and validated this panel in an independent cohort of 20 benign
      prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical
      evaluation in larger cohorts to help distinguish indolent PCa from advanced
      disease.

PMID- 23555184
TI  - Deconstruction of medulloblastoma cellular heterogeneity reveals differences
      between the most highly invasive and self-renewing phenotypes.
AB  - Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor.
      Major research efforts have focused on characterizing and targeting putative
      brain tumor stem or propagating cell populations from the tumor mass. However,
      less is known about the relationship between these cells and highly invasive MB
      cells that evade current therapies. Here, we dissected MB cellular heterogeneity
      and directly compared invasion and self-renewal. Analysis of higher versus lower
      self-renewing tumor spheres and stationary versus migrating adherent MB cells
      revealed differential expression of the cell surface markers CD271 [p75
      neurotrophin receptor (p75NTR)] and CD133. Cell sorting demonstrated that CD271
      selects for subpopulations with a higher capacity for self-renewal, whereas CD133
      selects for cells exhibiting increased invasion in vitro. CD271 expression is
      higher in human fetal cerebellum and primary samples of the Shh MB molecular
      variant and lower in the more aggressive, invasive group 3 and 4 subgroups.
      Global gene expression analysis of higher versus lower self-renewing MB tumor
      spheres revealed down-regulation of a cell movement transcription program in the
      higher self-renewing state and a novel potential role for axon guidance signaling
      in MB-propagating cells. We have identified a cell surface signature based on
      CD133/CD271 expression that selects for MB cells with a higher self-renewal
      potential or invasive capacity in vitro. Our study underscores a previously
      unappreciated role for CD271 in selecting for MB cell phenotypes and suggests
      that successful treatment of pediatric brain tumors requires concomitant
      targeting of a spectrum of transitioning self-renewing and highly infiltrative
      cell subpopulations.

PMID- 23555185
TI  - Methylation profiling defines an extensive field defect in histologically normal
      prostate tissues associated with prostate cancer.
AB  - Prostate cancer (PCa) is typically found as a multifocal disease suggesting the
      potential for molecular defects within the morphologically normal tissue. The
      frequency and spatial extent of DNA methylation changes encompassing a potential
      field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to
      histologically indistinguishable tumor-associated (TA) prostate tissues detected
      a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA
      arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene
      rich and poor regions. Hypomethylation (87%) occurred more frequently than
      hypermethylation (13%). Several of the most significantly altered loci (CAV1,
      EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA
      methylation changes in normal tissues from prostates containing cancer. In TA
      tissues, the extent of methylation was similar both adjacent (2 mm) and at a
      distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA
      from TA tissues in a validation set of patient samples. These mapping studies
      indicate that a spatially widespread epigenetic defect occurs in the peripheral
      prostate tissues of men who have PCa that may be useful in the detection of this
      disease.

PMID- 23555186
TI  - Interleukin-1beta promotes ovarian tumorigenesis through a p53/NF-kappaB-mediated
      inflammatory response in stromal fibroblasts.
AB  - Cancer has long been considered a disease that mimics an "unhealed wound," with
      oncogene-induced secretory activation signals from epithelial cancer cells
      facilitating stromal fibroblast, endothelial, and inflammatory cell participation
      in tumor progression. However, the underlying mechanisms that orchestrate
      cooperative interaction between malignant epithelium and the stroma remain
      largely unknown. Here, we identified interleukin-1beta (IL-1beta) as a stromal
      acting chemokine secreted by ovarian cancer cells, which suppresses p53 protein
      expression in cancer-associated fibroblasts (CAFs). Elevated expression of IL
      1beta and cognate receptor IL-1R1 in ovarian cancer epithelial cells and CAFs
      independently predicted reduced overall patient survival, as did repressed
      nuclear p53 in ovarian CAFs. Knockdown of p53 expression in ovarian fibroblasts
      significantly enhanced the expression and secretion of chemokines IL-8, growth
      regulated oncogene-alpha (GRO-alpha), IL-6, IL-1beta, and vascular endothelial
      growth factor (VEGF), significantly increased in vivo mouse xenograft ovarian
      cancer tumor growth, and was entirely dependent on interaction with, and
      transcriptional up-regulation of, nuclear factor-kappaB (NF-kappaB) p65. Our
      results have uncovered a previously unrecognized circuit whereby epithelial
      cancer cells use IL-1beta as a communication factor instructing stromal
      fibroblasts through p53 to generate a protumorigenic inflammatory
      microenvironment. Attenuation of p53 protein expression in stromal fibroblasts
      generates critical protumorigenic functionality, reminiscent of the role that
      oncogenic p53 mutations play in cancer cells. These findings implicate CAFs as an
      important target for blocking inflammation in the tumor microenvironment and
      reducing tumor growth.

PMID- 23555187
TI  - gamma-Catenin at adherens junctions: mechanism and biologic implications in
      hepatocellular cancer after beta-catenin knockdown.
AB  - beta-Catenin is important in liver homeostasis as a part of Wnt signaling and
      adherens junctions (AJs), while its aberrant activation is observed in
      hepatocellular carcinoma (HCC). We have reported hepatocyte-specific beta-catenin
      knockout (KO) mice to lack adhesive defects as gamma-catenin compensated at AJ.
      Because gamma-catenin is a desmosomal protein, we asked if its increase in KO
      might deregulate desmosomes. No changes in desmosomal proteins or ultrastructure
      other than increased plakophilin-3 were observed. To further elucidate the role
      and regulation of gamma-catenin, we contemplate an in vitro model and show gamma
      catenin increase in HCC cells upon beta-catenin knockdown (KD). Here, gamma
      catenin is unable to rescue beta-catenin/T cell factor (TCF) reporter activity;
      however, it sufficiently compensates at AJs as assessed by scratch wound assay,
      centrifugal assay for cell adhesion (CAFCA), and hanging drop assays. gamma
      Catenin increase is observed only after beta-catenin protein decrease and not
      after blockade of its transactivation. gamma-Catenin increase is associated with
      enhanced serine/threonine phosphorylation and abrogated by protein kinase A (PKA)
      inhibition. In fact, several PKA-binding sites were detected in gamma-catenin by
      in silico analysis. Intriguingly gamma-catenin KD led to increased beta-catenin
      levels and transactivation. Thus, gamma-catenin compensates for beta-catenin loss
      at AJ without affecting desmosomes but is unable to fulfill functions in Wnt
      signaling. gamma-Catenin stabilization after beta-catenin loss is brought about
      by PKA. Catenin-sensing mechanism may depend on absolute beta-catenin levels and
      not its activity. Anti-beta-catenin therapies for HCC affecting total beta
      catenin may target aberrant Wnt signaling without negatively impacting
      intercellular adhesion, provided mechanisms leading to gamma-catenin
      stabilization are spared.

PMID- 23555188
TI  - Genotype and tumor locus determine expression profile of pseudohypoxic
      pheochromocytomas and paragangliomas.
AB  - Pheochromocytomas (PHEOs) and paragangliomas (PGLs) related to mutations in the
      mitochondrial succinate dehydrogenase (SDH) subunits A, B, C, and D, SDH complex
      assembly factor 2, and the von Hippel-Lindau (VHL) genes share a pseudohypoxic
      expression profile. However, genotype-specific differences in expression have
      been emerging. Development of effective new therapies for distinctive
      manifestations, e.g., a high rate of malignancy in SDHB- or predisposition to
      multifocal PGLs in SDHD patients, mandates improved stratification. To identify
      mutation/location-related characteristics among pseudohypoxic PHEOs/PGLs, we used
      comprehensive microarray profiling (SDHB: n = 18, SDHD-abdominal/thoracic (AT): n
      = 6, SDHD-head/neck (HN): n = 8, VHL: n = 13). To avoid location-specific bias,
      typical adrenal medulla genes were derived from matched normal medullas and
      cortices (n = 8) for data normalization. Unsupervised analysis identified two
      dominant clusters, separating SDHB and SDHD-AT PHEOs/PGLs (cluster A) from VHL
      PHEOs and SDHD-HN PGLs (cluster B). Supervised analysis yielded 6937 highly
      predictive genes (misclassification error rate of 0.175). Enrichment analysis
      revealed that energy metabolism and inflammation/fibrosis-related genes were most
      pronouncedly changed in clusters A and B, respectively. A minimum subset of 40
      classifiers was validated by quantitative real-time polymerase chain reaction
      (quantitative real-time polymerase chain reaction vs. microarray: r = 0.87).
      Expression of several individual classifiers was identified as characteristic for
      VHL and SDHD-HN PHEOs and PGLs. In the present study, we show for the first time
      that SDHD-HN PGLs share more features with VHL PHEOs than with SDHD-AT PGLs. The
      presented data suggest novel subclassification of pseudohypoxic PHEOs/PGLs and
      implies cluster-specific pathogenic mechanisms and treatment strategies.

PMID- 23555189
TI  - Genome-wide association study identifies genetic determinants of urine PCA3
      levels in men.
AB  - Prostate cancer gene 3 (PCA3) is a non-coding gene specifically overexpressed in
      prostate cancer (PCa) that has great potential as a clinical biomarker for
      predicting prostate biopsy outcome. However, genetic determinants of PCA3
      expression level remain unknown. To investigate the association between genetic
      variants and PCA3 mRNA level, a genome-wide association study was conducted in
      1371 men of European descent in the REduction by DUtasteride of prostate Cancer
      Events trial. First-voided urine specimens containing prostate cells were
      obtained after digital rectal examination. The PROGENSA PCA3 assay was used to
      determine PCA3 score in the urinary samples. A linear regression model was used
      to detect the associations between (single nucleotide polymorphisms) SNPs and
      PCA3 score under an additive genetic model, adjusting for age and population
      stratification. Two SNPs, rs10993994 in beta-microseminoprotein at 10q11.23 and
      rs10424878 in kallikrein-related peptidase 2 at 19q13.33, were associated with
      PCA3 score at genome-wide significance level (P = 1.22 x 10(-9) and 1.06 x 10(
      8), respectively). Men carrying the rs10993994 "T" allele or rs10424878 "A"
      allele had higher PCA3 score compared with men carrying rs10993994 "C" allele or
      rs10424878 "G" allele (beta = 1.25 and 1.24, respectively). This is the first
      comprehensive search for genetic determinants of PCA3 score. The novel loci
      identified may provide insight into the molecular mechanisms of PCA3 expression
      as a potential marker of PCa.

PMID- 23555190
TI  - Adenomatous polyposis coli-mediated accumulation of abasic DNA lesions lead to
      cigarette smoke condensate-induced neoplastic transformation of normal breast
      epithelial cells.
AB  - Adenomatous polyposis coli (APC) is a multifunctional protein having diverse
      cellular functions including cell migration, cell-cell adhesion, cell cycle
      control, chromosomal segregation, and apoptosis. Recently, we found a new role of
      APC in base excision repair (BER) and showed that it interacts with DNA
      polymerase beta and 5'-flap endonuclease 1 and interferes in BER. Previously, we
      have also reported that cigarette smoke condensate (CSC) increases expression of
      APC and enhances the growth of normal human breast epithelial (MCF10A) cells in
      vitro. In the present study, using APC overexpression and knockdown systems, we
      have examined the molecular mechanisms by which CSC and its major component,
      Benzo[alpha]pyrene, enhances APC-mediated accumulation of abasic DNA lesions,
      which is cytotoxic and mutagenic in nature, leading to enhanced neoplastic
      transformation of MCF10A cells in an orthotopic xenograft model.

PMID- 23555191
TI  - Selecting one of several mating types through gene segment joining and deletion
      in Tetrahymena thermophila.
AB  - The unicellular eukaryote Tetrahymena thermophila has seven mating types. Cells
      can mate only when they recognize cells of a different mating type as non-self.
      As a ciliate, Tetrahymena separates its germline and soma into two nuclei. During
      growth the somatic nucleus is responsible for all gene transcription while the
      germline nucleus remains silent. During mating, a new somatic nucleus is
      differentiated from a germline nucleus and mating type is decided by a stochastic
      process. We report here that the somatic mating type locus contains a pair of
      genes arranged head-to-head. Each gene encodes a mating type-specific segment and
      a transmembrane domain that is shared by all mating types. Somatic gene knockouts
      showed both genes are required for efficient non-self recognition and successful
      mating, as assessed by pair formation and progeny production. The germline mating
      type locus consists of a tandem array of incomplete gene pairs representing each
      potential mating type. During mating, a complete new gene pair is assembled at
      the somatic mating type locus; the incomplete genes of one gene pair are
      completed by joining to gene segments at each end of germline array. All other
      germline gene pairs are deleted in the process. These programmed DNA
      rearrangements make this a fascinating system of mating type determination.

PMID- 23555192
TI  - Caring for offspring in a world of cheats.
AB  - Parents providing care to offspring face the same problem that exists in every
      biological system in which some individuals offer resources to others: cheaters,
      who exploit these benefits. In almost all species in which males contribute to
      parental care, females mate with multiple males. As a result, males frequently
      provide efforts for unrelated offspring at a cost to their own reproductive
      fitness. In a new study, Griffin et al. find that across a wide range of animal
      species, males flexibly adjust their contribution to parental care in relation to
      extra-pair paternity. However, adjustment is not perfect, because males are
      limited by the potential costs of withholding help to their own offspring, which
      is only outweighed if cheating occurs frequently and if providing care reduces a
      male's future reproductive success. These findings illustrate how in biological
      systems cheater and cheated can adapt to changes in each other, preventing either
      one from gaining control.

PMID- 23555193
TI  - Why do cuckolded males provide paternal care?
AB  - In most species, males do not abandon offspring or reduce paternal care when they
      are cuckolded by other males. This apparent lack of adjustment of paternal
      investment with the likelihood of paternity presents a potential challenge to our
      understanding of what drives selection for paternal care. In a comparative
      analysis across birds, fish, mammals, and insects we identify key factors that
      explain why cuckolded males in many species do not reduce paternal care.
      Specifically, we show that cuckolded males only reduce paternal investment if
      both the costs of caring are relatively high and there is a high risk of
      cuckoldry. Under these circumstances, selection is expected to favour males that
      reduce paternal effort in response to cuckoldry. In many species, however, these
      conditions are not satisfied and tolerant males have outcompeted males that
      abandon young.

PMID- 23555194
TI  - Mating type determination in tetrahymena: last man standing.

PMID- 23555195
TI  - A conserved role for human Nup98 in altering chromatin structure and promoting
      epigenetic transcriptional memory.
AB  - The interaction of nuclear pore proteins (Nups) with active genes can promote
      their transcription. In yeast, some inducible genes interact with the nuclear
      pore complex both when active and for several generations after being repressed,
      a phenomenon called epigenetic transcriptional memory. This interaction promotes
      future reactivation and requires Nup100, a homologue of human Nup98. A similar
      phenomenon occurs in human cells; for at least four generations after treatment
      with interferon gamma (IFN-gamma), many IFN-gamma-inducible genes are induced
      more rapidly and more strongly than in cells that have not previously been
      exposed to IFN-gamma. In both yeast and human cells, the recently expressed
      promoters of genes with memory exhibit persistent dimethylation of histone H3
      lysine 4 (H3K4me2) and physically interact with Nups and a poised form of RNA
      polymerase II. However, in human cells, unlike yeast, these interactions occur in
      the nucleoplasm. In human cells transiently depleted of Nup98 or yeast cells
      lacking Nup100, transcriptional memory is lost; RNA polymerase II does not remain
      associated with promoters, H3K4me2 is lost, and the rate of transcriptional
      reactivation is reduced. These results suggest that Nup100/Nup98 binding to
      recently expressed promoters plays a conserved role in promoting epigenetic
      transcriptional memory.

PMID- 23555196
TI  - White-opaque switching in natural MTLa/alpha isolates of Candida albicans:
      evolutionary implications for roles in host adaptation, pathogenesis, and sex.
AB  - Phenotypic transitions play critical roles in host adaptation, virulence, and
      sexual reproduction in pathogenic fungi. A minority of natural isolates of
      Candida albicans, which are homozygous at the mating type locus (MTL, a/a or
      alpha/alpha), are known to be able to switch between two distinct cell types:
      white and opaque. It is puzzling that white-opaque switching has never been
      observed in the majority of natural C. albicans strains that have heterozygous
      MTL genotypes (a/alpha), given that they contain all of the opaque-specific genes
      essential for switching. Here we report the discovery of white-opaque switching
      in a number of natural a/alpha strains of C. albicans under a condition mimicking
      aspects of the host environment. The optimal condition for white-to-opaque
      switching in a/alpha strains of C. albicans is to use N-acetylglucosamine
      (GlcNAc) as the sole carbon source and to incubate the cells in 5% CO2. Although
      the induction of white-to-opaque switching in a/alpha strains of C. albicans is
      not as robust as in MTL homozygotes in response to GlcNAc and CO2, opaque cells
      of a/alpha strains exhibit similar features of cellular and colony morphology to
      their MTL homozygous counterparts. Like MTL homozygotes, white and opaque cells
      of a/alpha strains differ in their behavior in different mouse infection models.
      We have further demonstrated that the transcriptional regulators Rfg1, Brg1, and
      Efg1 are involved in the regulation of white-to-opaque switching in a/alpha
      strains. We propose that the integration of multiple environmental cues and the
      activation and inactivation of a set of transcriptional regulators controls the
      expression of the master switching regulator WOR1, which determines the final
      fate of the cell type in C. albicans. Our discovery of white-opaque switching in
      the majority of natural a/alpha strains of C. albicans emphasizes its widespread
      nature and importance in host adaptation, pathogenesis, and parasexual
      reproduction.

PMID- 23555197
TI  - Research misconduct in low- and middle-income countries.
AB  - As part of a cluster of articles critically reflecting on the theme of "no health
      without research," Richard Smith and colleagues lay out what is currently known
      about research misconduct in low- and middle-income countries, summarizing some
      high profile cases and making suggestions on ways forward.

PMID- 23555198
TI  - Policies and initiatives aimed at addressing research misconduct in high-income
      countries.
AB  - David Resnik and Zubin Master review current policies and initiatives for
      preventing and managing research misconduct in high-income countries, summarize
      some high profile cases of misconduct, and make suggestions on ways forward.

PMID- 23555199
TI  - Getting closer to a fully correctable and connected research literature.
AB  - The PLOS Medicine Editors discuss the need for a dynamic publishing system that
      enables linkage to corrections of errors in scientific literature (whatever their
      source) and full integration of articles with post-publication commentary.

PMID- 23555200
TI  - Young children's probability of dying before and after their mother's death: a
      rural South African population-based surveillance study.
AB  - BACKGROUND: There is evidence that a young child's risk of dying increases
      following the mother's death, but little is known about the risk when the mother
      becomes very ill prior to her death. We hypothesized that children would be more
      likely to die during the period several months before their mother's death, as
      well as for several months after her death. Therefore we investigated the
      relationship between young children's likelihood of dying and the timing of their
      mother's death and, in particular, the existence of a critical period of
      increased risk. METHODS AND FINDINGS: Data from a health and socio-demographic
      surveillance system in rural South Africa were collected on children 0-5 y of age
      from 1 January 1994 to 31 December 2008. Discrete time survival analysis was used
      to estimate children's probability of dying before and after their mother's
      death, accounting for moderators. 1,244 children (3% of sample) died from 1994 to
      2008. The probability of child death began to rise 6-11 mo prior to the mother's
      death and increased markedly during the 2 mo immediately before the month of her
      death (odds ratio [OR] 7.1 [95% CI 3.9-12.7]), in the month of her death (OR 12.6
      [6.2-25.3]), and during the 2 mo following her death (OR 7.0 [3.2-15.6]). This
      increase in the probability of dying was more pronounced for children whose
      mothers died of AIDS or tuberculosis compared to other causes of death, but the
      pattern remained for causes unrelated to AIDS/tuberculosis. Infants aged 0-6 mo
      at the time of their mother's death were nine times more likely to die than
      children aged 2-5 y. The limitations of the study included the lack of knowledge
      about precisely when a very ill mother will die, a lack of information about
      child nutrition and care, and the diagnosis of AIDS deaths by verbal autopsy
      rather than serostatus. CONCLUSIONS: Young children in lower income settings are
      more likely to die not only after their mother's death but also in the months
      before, when she is seriously ill. Interventions are urgently needed to support
      families both when the mother becomes very ill and after her death. Please see
      later in the article for the Editors' Summary.

PMID- 23555201
TI  - Changing patterns in place of cancer death in England: a population-based study.
AB  - BACKGROUND: Most patients with cancer prefer to die at home or in a hospice, but
      hospitals remain the most common place of death (PoD).This study aims to explore
      the changing time trends of PoD and the associated factors, which are essential
      for end-of-life care improvement. METHODS AND FINDINGS: The study analysed all
      cancer deaths in England collected by the Office for National Statistics during
      1993-2010 (n = 2,281,223). Time trends of age- and gender-standardised proportion
      of deaths in individual PoDs were evaluated using weighted piecewise linear
      regression. Variables associated with PoD (home or hospice versus hospital) were
      determined using proportion ratio (PR) derived from the log-binomial regression,
      adjusting for clustering effects. Hospital remained the most common PoD
      throughout the study period (48.0%; 95% CI 47.9%-48.0%), followed by home (24.5%;
      95% CI 24.4%-24.5%), and hospice (16.4%; 95% CI 16.3%-16.4%). Home and hospice
      deaths increased since 2005 (0.87%; 95% CI 0.74%-0.99%/year, 0.24%; 95% CI 0.17%
      0.32%/year, respectively, p<0.001), while hospital deaths declined (-1.20%; 95%
      CI -1.41 to -0.99/year, p<0.001). Patients who died from haematological cancer
      (PRs 0.46-0.52), who were single, widowed, or divorced (PRs 0.75-0.88), and aged
      over 75 (PRs 0.81-0.84 for 75-84; 0.66-0.72 for 85+) were less likely to die in
      home or hospice (p<0.001; reference groups: colorectal cancer, married, age 25
      54). There was little improvement in patients with lung cancer of dying in home
      or hospice (PRs 0.87-0.88). Marital status became the second most important
      factor associated with PoD, after cancer type. Patients from less deprived areas
      (higher quintile of the deprivation index) were more likely to die at home or in
      a hospice than those from more deprived areas (lower quintile of the deprivation
      index; PRs 1.02-1.12). The analysis is limited by a lack of data on individual
      patients' preferences for PoD or a clinical indication of the most appropriate
      PoD. CONCLUSIONS: More efforts are needed to reduce hospital deaths. Health care
      facilities should be improved and enhanced to support the increased home and
      hospice deaths. People who are single, widowed, or divorced should be a focus for
      end-of-life care improvement, along with known at risk groups such as
      haematological cancer, lung cancer, older age, and deprivation. Please see later
      in the article for the Editors' Summary.

PMID- 23555202
TI  - Do ants need to estimate the geometrical properties of trail bifurcations to find
      an efficient route? A swarm robotics test bed.
AB  - Interactions between individuals and the structure of their environment play a
      crucial role in shaping self-organized collective behaviors. Recent studies have
      shown that ants crossing asymmetrical bifurcations in a network of galleries tend
      to follow the branch that deviates the least from their incoming direction. At
      the collective level, the combination of this tendency and the pheromone-based
      recruitment results in a greater likelihood of selecting the shortest path
      between the colony's nest and a food source in a network containing asymmetrical
      bifurcations. It was not clear however what the origin of this behavioral bias
      is. Here we propose that it results from a simple interaction between the
      behavior of the ants and the geometry of the network, and that it does not
      require the ability to measure the angle of the bifurcation. We tested this
      hypothesis using groups of ant-like robots whose perceptual and cognitive
      abilities can be fully specified. We programmed them only to lay down and follow
      light trails, avoid obstacles and move according to a correlated random walk, but
      not to use more sophisticated orientation methods. We recorded the behavior of
      the robots in networks of galleries presenting either only symmetrical
      bifurcations or a combination of symmetrical and asymmetrical bifurcations.
      Individual robots displayed the same pattern of branch choice as individual ants
      when crossing a bifurcation, suggesting that ants do not actually measure the
      geometry of the bifurcations when travelling along a pheromone trail. Finally at
      the collective level, the group of robots was more likely to select one of the
      possible shorter paths between two designated areas when moving in an
      asymmetrical network, as observed in ants. This study reveals the importance of
      the shape of trail networks for foraging in ants and emphasizes the
      underestimated role of the geometrical properties of transportation networks in
      general.

PMID- 23555204
TI  - A discriminative approach for unsupervised clustering of DNA sequence motifs.
AB  - Algorithmic comparison of DNA sequence motifs is a problem in bioinformatics that
      has received increased attention during the last years. Its main applications
      concern characterization of potentially novel motifs and clustering of a motif
      collection in order to remove redundancy. Despite growing interest in motif
      clustering, the question which motif clusters to aim at has so far not been
      systematically addressed. Here we analyzed motif similarities in a comprehensive
      set of vertebrate transcription factor classes. For this we developed enhanced
      similarity scores by inclusion of the information coverage (IC) criterion, which
      evaluates the fraction of information an alignment covers in aligned motifs. A
      network-based method enabled us to identify motif clusters with high
      correspondence to DNA-binding domain phylogenies and prior experimental findings.
      Based on this analysis we derived a set of motif families representing distinct
      binding specificities. These motif families were used to train a classifier which
      was further integrated into a novel algorithm for unsupervised motif clustering.
      Application of the new algorithm demonstrated its superiority to previously
      published methods and its ability to reproduce entrained motif families. As a
      result, our work proposes a probabilistic approach to decide whether two motifs
      represent common or distinct binding specificities.

PMID- 23555203
TI  - Viral phylodynamics.
AB  - Viral phylodynamics is defined as the study of how epidemiological,
      immunological, and evolutionary processes act and potentially interact to shape
      viralphylogenies. Since the coining of the term in 2004, research on viral
      phylodynamics has focused on transmission dynamics in an effort to shed light on
      how these dynamics impact viral genetic variation. Transmission dynamics can be
      considered at the level of cells within an infected host, individual hosts within
      a population, or entire populations of hosts. Many viruses, especially RNA
      viruses, rapidly accumulate genetic variation because of short generation times
      and high mutation rates. Patterns of viral genetic variation are therefore
      heavily influenced by how quickly transmission occurs and by which entities
      transmit to one another. Patterns of viral genetic variation will also be
      affected by selection acting on viral phenotypes. Although viruses can differ
      with respect to many phenotypes, phylodynamic studies have to date tended to
      focus on a limited number of viral phenotypes. These include virulence
      phenotypes, phenotypes associated with viral transmissibility, cell or tissue
      tropism phenotypes, and antigenic phenotypes that can facilitate escape from host
      immunity. Due to the impact that transmission dynamics and selection can have on
      viral genetic variation, viral phylogenies can therefore be used to investigate
      important epidemiological, immunological, and evolutionary processes, such as
      epidemic spread[2], spatio-temporal dynamics including metapopulation
      dynamics[3], zoonotic transmission, tissue tropism[4], and antigenic drift[5].
      The quantitative investigation of these processes through the consideration of
      viral phylogenies is the central aim of viral phylodynamics.

PMID- 23555205
TI  - Combined model of intrinsic and extrinsic variability for computational network
      design with application to synthetic biology.
AB  - Biological systems are inherently variable, with their dynamics influenced by
      intrinsic and extrinsic sources. These systems are often only partially
      characterized, with large uncertainties about specific sources of extrinsic
      variability and biochemical properties. Moreover, it is not yet well understood
      how different sources of variability combine and affect biological systems in
      concert. To successfully design biomedical therapies or synthetic circuits with
      robust performance, it is crucial to account for uncertainty and effects of
      variability. Here we introduce an efficient modeling and simulation framework to
      study systems that are simultaneously subject to multiple sources of variability,
      and apply it to make design decisions on small genetic networks that play a role
      of basic design elements of synthetic circuits. Specifically, the framework was
      used to explore the effect of transcriptional and post-transcriptional
      autoregulation on fluctuations in protein expression in simple genetic networks.
      We found that autoregulation could either suppress or increase the output
      variability, depending on specific noise sources and network parameters. We
      showed that transcriptional autoregulation was more successful than post
      transcriptional in suppressing variability across a wide range of intrinsic and
      extrinsic magnitudes and sources. We derived the following design principles to
      guide the design of circuits that best suppress variability: (i) high protein
      cooperativity and low miRNA cooperativity, (ii) imperfect complementarity between
      miRNA and mRNA was preferred to perfect complementarity, and (iii) correlated
      expression of mRNA and miRNA--for example, on the same transcript--was best for
      suppression of protein variability. Results further showed that correlations in
      kinetic parameters between cells affected the ability to suppress variability,
      and that variability in transient states did not necessarily follow the same
      principles as variability in the steady state. Our model and findings provide a
      general framework to guide design principles in synthetic biology.

PMID- 23555206
TI  - Multi-scale inference of interaction rules in animal groups using Bayesian model
      selection.
AB  - Inference of interaction rules of animals moving in groups usually relies on an
      analysis of large scale system behaviour. Models are tuned through repeated
      simulation until they match the observed behaviour. More recent work has used the
      fine scale motions of animals to validate and fit the rules of interaction of
      animals in groups. Here, we use a Bayesian methodology to compare a variety of
      models to the collective motion of glass prawns (Paratya australiensis). We show
      that these exhibit a stereotypical 'phase transition', whereby an increase in
      density leads to the onset of collective motion in one direction. We fit models
      to this data, which range from: a mean-field model where all prawns interact
      globally; to a spatial Markovian model where prawns are self-propelled particles
      influenced only by the current positions and directions of their neighbours; up
      to non-Markovian models where prawns have 'memory' of previous interactions,
      integrating their experiences over time when deciding to change behaviour. We
      show that the mean-field model fits the large scale behaviour of the system, but
      does not capture the observed locality of interactions. Traditional self
      propelled particle models fail to capture the fine scale dynamics of the system.
      The most sophisticated model, the non-Markovian model, provides a good match to
      the data at both the fine scale and in terms of reproducing global dynamics,
      while maintaining a biologically plausible perceptual range. We conclude that
      prawns' movements are influenced by not just the current direction of nearby
      conspecifics, but also those encountered in the recent past. Given the simplicity
      of prawns as a study system our research suggests that self-propelled particle
      models of collective motion should, if they are to be realistic at multiple
      biological scales, include memory of previous interactions and other non
      Markovian effects.

PMID- 23555207
TI  - Optimal vaccine allocation for the early mitigation of pandemic influenza.
AB  - With new cases of avian influenza H5N1 (H5N1AV) arising frequently, the threat of
      a new influenza pandemic remains a challenge for public health. Several vaccines
      have been developed specifically targeting H5N1AV, but their production is
      limited and only a few million doses are readily available. Because there is an
      important time lag between the emergence of new pandemic strain and the
      development and distribution of a vaccine, shortage of vaccine is very likely at
      the beginning of a pandemic. We coupled a mathematical model with a genetic
      algorithm to optimally and dynamically distribute vaccine in a network of cities,
      connected by the airline transportation network. By minimizing the illness attack
      rate (i.e., the percentage of people in the population who become infected and
      ill), we focus on optimizing vaccine allocation in a network of 16 cities in
      Southeast Asia when only a few million doses are available. In our base case, we
      assume the vaccine is well-matched and vaccination occurs 5 to 10 days after the
      beginning of the epidemic. The effectiveness of all the vaccination strategies
      drops off as the timing is delayed or the vaccine is less well-matched. Under the
      best assumptions, optimal vaccination strategies substantially reduced the
      illness attack rate, with a maximal reduction in the attack rate of 85%.
      Furthermore, our results suggest that cooperative strategies where the resources
      are optimally distributed among the cities perform much better than the
      strategies where the vaccine is equally distributed among the network, yielding
      an illness attack rate 17% lower. We show that it is possible to significantly
      mitigate a more global epidemic with limited quantities of vaccine, provided that
      the vaccination campaign is extremely fast and it occurs within the first weeks
      of transmission.

PMID- 23555208
TI  - The fidelity of dynamic signaling by noisy biomolecular networks.
AB  - Cells live in changing, dynamic environments. To understand cellular decision
      making, we must therefore understand how fluctuating inputs are processed by
      noisy biomolecular networks. Here we present a general methodology for analyzing
      the fidelity with which different statistics of a fluctuating input are
      represented, or encoded, in the output of a signaling system over time. We
      identify two orthogonal sources of error that corrupt perfect representation of
      the signal: dynamical error, which occurs when the network responds on average to
      other features of the input trajectory as well as to the signal of interest, and
      mechanistic error, which occurs because biochemical reactions comprising the
      signaling mechanism are stochastic. Trade-offs between these two errors can
      determine the system's fidelity. By developing mathematical approaches to derive
      dynamics conditional on input trajectories we can show, for example, that
      increased biochemical noise (mechanistic error) can improve fidelity and that
      both negative and positive feedback degrade fidelity, for standard models of
      genetic autoregulation. For a group of cells, the fidelity of the collective
      output exceeds that of an individual cell and negative feedback then typically
      becomes beneficial. We can also predict the dynamic signal for which a given
      system has highest fidelity and, conversely, how to modify the network design to
      maximize fidelity for a given dynamic signal. Our approach is general, has
      applications to both systems and synthetic biology, and will help underpin
      studies of cellular behavior in natural, dynamic environments.

PMID- 23555209
TI  - Explaining the determinants of first phase HIV decay dynamics through the effects
      of stage-dependent drug action.
AB  - A recent investigation of the effect of different antiretroviral drug classes on
      first phase dynamics of HIV RNA plasma virus levels has indicated that drugs
      acting at stages closer to viral production, such as the integrase inhibitor
      raltegravir, can produce a steeper first phase decay slope that may not be due to
      drug efficacy. Moreover it was found that for most drug classes the first phase
      transitions from a faster (phase IA) to a slightly slower decay region (phase IB)
      before the start of the usual second phase. Neither of these effects has been
      explained to date. We use a mathematical model that incorporates the different
      stages of the HIV viral life cycle in CD4+ T cells: viral entry, reverse
      transcription, integration, and viral production, to investigate the
      intracellular HIV mechanisms responsible for these complex plasma virus decay
      dynamics. We find differences in the phase IA slope across drug classes arise
      from a higher death rate of cells when they enter the productively infected stage
      post-integration, with a half-life of approximately 8 hours in this stage,
      whereas cells in earlier stages of the infection cycle have half-lives similar to
      uninfected cells. This implies any immune clearance is predominantly limited to
      the productive infection stage. We also show that the slowing of phase IA to
      phase IB at day 2 to 4 of monotherapy, depending on drug class, is a result of
      new rounds of infection. The level at which this slowing occurs is a better
      indicator of drug efficacy than the slope of the initial decay.

PMID- 23555210
TI  - Bayesian estimation of mixture models with prespecified elements to compare drug
      resistance in treatment-naive and experienced tuberculosis cases.
AB  - We propose a Bayesian approach for estimating branching tree mixture models to
      compare drug-resistance pathways (i.e. patterns of sequential acquisition of
      resistance to individual antibiotics) that are observed among Mycobacterium
      tuberculosis isolates collected from treatment-naive and treatment-experienced
      patients. Resistant pathogens collected from treatment-naive patients are strains
      for which fitness costs of resistance were not sufficient to prevent
      transmission, whereas those collected from treatment-experienced patients reflect
      both transmitted and acquired resistance, the latter of which may or may not be
      associated with lower transmissibility. The comparison of the resistance pathways
      constructed from these two groups of drug-resistant strains provides insight into
      which pathways preferentially lead to the development of multiple drug resistant
      strains that are transmissible. We apply the proposed statistical methods to data
      from worldwide surveillance of drug-resistant tuberculosis collected by the World
      Health Organization over 13 years.

PMID- 23555211
TI  - Bursts of vertex activation and epidemics in evolving networks.
AB  - The dynamic nature of contact patterns creates diverse temporal structures. In
      particular, empirical studies have shown that contact patterns follow
      heterogeneous inter-event time intervals, meaning that periods of high activity
      are followed by long periods of inactivity. To investigate the impact of these
      heterogeneities in the spread of infection from a theoretical perspective, we
      propose a stochastic model to generate temporal networks where vertices make
      instantaneous contacts following heterogeneous inter-event intervals, and may
      leave and enter the system. We study how these properties affect the prevalence
      of an infection and estimate R(0), the number of secondary infections of an
      infectious individual in a completely susceptible population, by modeling
      simulated infections (SI and SIR) that co-evolve with the network structure. We
      find that heterogeneous contact patterns cause earlier and larger epidemics in
      the SIR model in comparison to homogeneous scenarios for a vast range of
      parameter values, while smaller epidemics may happen in some combinations of
      parameters. In the case of SI and heterogeneous patterns, the epidemics develop
      faster in the earlier stages followed by a slowdown in the asymptotic limit. For
      increasing vertex turnover rates, heterogeneous patterns generally cause higher
      prevalence in comparison to homogeneous scenarios with the same average inter
      event interval. We find that [Formula: see text] is generally higher for
      heterogeneous patterns, except for sufficiently large infection duration and
      transmission probability.

PMID- 23555212
TI  - Network-based survival analysis reveals subnetwork signatures for predicting
      outcomes of ovarian cancer treatment.
AB  - Cox regression is commonly used to predict the outcome by the time to an event of
      interest and in addition, identify relevant features for survival analysis in
      cancer genomics. Due to the high-dimensionality of high-throughput genomic data,
      existing Cox models trained on any particular dataset usually generalize poorly
      to other independent datasets. In this paper, we propose a network-based Cox
      regression model called Net-Cox and applied Net-Cox for a large-scale survival
      analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network
      information into the Cox's proportional hazard model to explore the co-expression
      or functional relation among high-dimensional gene expression features in the
      gene network. Net-Cox was applied to analyze three independent gene expression
      datasets including the TCGA ovarian cancer dataset and two other public ovarian
      cancer datasets. Net-Cox with the network information from gene co-expression or
      functional relations identified highly consistent signature genes across the
      three datasets, and because of the better generalization across the datasets, Net
      Cox also consistently improved the accuracy of survival prediction over the Cox
      models regularized by L(2) or L(1). This study focused on analyzing the death and
      recurrence outcomes in the treatment of ovarian carcinoma to identify signature
      genes that can more reliably predict the events. The signature genes comprise
      dense protein-protein interaction subnetworks, enriched by extracellular matrix
      receptors and modulators or by nuclear signaling components downstream of
      extracellular signal-regulated kinases. In the laboratory validation of the
      signature genes, a tumor array experiment by protein staining on an independent
      patient cohort from Mayo Clinic showed that the protein expression of the
      signature gene FBN1 is a biomarker significantly associated with the early
      recurrence after 12 months of the treatment in the ovarian cancer patients who
      are initially sensitive to chemotherapy. Net-Cox toolbox is available at
      http://compbio.cs.umn.edu/Net-Cox/.

PMID- 23555213
TI  - Automated analysis of a diverse synapse population.
AB  - Synapses of the mammalian central nervous system are highly diverse in function
      and molecular composition. Synapse diversity per se may be critical to brain
      function, since memory and homeostatic mechanisms are thought to be rooted
      primarily in activity-dependent plastic changes in specific subsets of individual
      synapses. Unfortunately, the measurement of synapse diversity has been restricted
      by the limitations of methods capable of measuring synapse properties at the
      level of individual synapses. Array tomography is a new high-resolution, high
      throughput proteomic imaging method that has the potential to advance the
      measurement of unit-level synapse diversity across large and diverse synapse
      populations. Here we present an automated feature extraction and classification
      algorithm designed to quantify synapses from high-dimensional array tomographic
      data too voluminous for manual analysis. We demonstrate the use of this method to
      quantify laminar distributions of synapses in mouse somatosensory cortex and
      validate the classification process by detecting the presence of known but
      uncommon proteomic profiles. Such classification and quantification will be
      highly useful in identifying specific subpopulations of synapses exhibiting
      plasticity in response to perturbations from the environment or the sensory
      periphery.

PMID- 23555214
TI  - Analysis of physicochemical and structural properties determining HIV-1
      coreceptor usage.
AB  - The relationship of HIV tropism with disease progression and the recent
      development of CCR5-blocking drugs underscore the importance of monitoring virus
      coreceptor usage. As an alternative to costly phenotypic assays, computational
      methods aim at predicting virus tropism based on the sequence and structure of
      the V3 loop of the virus gp120 protein. Here we present a numerical descriptor of
      the V3 loop encoding its physicochemical and structural properties. The
      descriptor allows for structure-based prediction of HIV tropism and
      identification of properties of the V3 loop that are crucial for coreceptor
      usage. Use of the proposed descriptor for prediction results in a statistically
      significant improvement over the prediction based solely on V3 sequence with 3
      percentage points improvement in AUC and 7 percentage points in sensitivity at
      the specificity of the 11/25 rule (95%). We additionally assessed the predictive
      power of the new method on clinically derived 'bulk' sequence data and obtained a
      statistically significant improvement in AUC of 3 percentage points over sequence
      based prediction. Furthermore, we demonstrated the capacity of our method to
      predict therapy outcome by applying it to 53 samples from patients undergoing
      Maraviroc therapy. The analysis of structural features of the loop informative of
      tropism indicates the importance of two loop regions and their physicochemical
      properties. The regions are located on opposite strands of the loop stem and the
      respective features are predominantly charge-, hydrophobicity- and structure
      related. These regions are in close proximity in the bound conformation of the
      loop potentially forming a site determinant for the coreceptor binding. The
      method is available via server under http://structure.bioinf.mpi-inf.mpg.de/.

PMID- 23555215
TI  - The RAVEN toolbox and its use for generating a genome-scale metabolic model for
      Penicillium chrysogenum.
AB  - We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic
      Networks) Toolbox: a software suite that allows for semi-automated reconstruction
      of genome-scale models. It makes use of published models and/or the KEGG
      database, coupled with extensive gap-filling and quality control features. The
      software suite also contains methods for visualizing simulation results and omics
      data, as well as a range of methods for performing simulations and analyzing the
      results. The software is a useful tool for system-wide data analysis in a
      metabolic context and for streamlined reconstruction of metabolic networks based
      on protein homology. The RAVEN Toolbox workflow was applied in order to
      reconstruct a genome-scale metabolic model for the important microbial cell
      factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a
      bibliomic study of in total 440 references, and it comprises 1471 unique
      biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP
      and NADPH in the biosynthesis of penicillin, and to identify potential metabolic
      engineering targets for maximization of penicillin production.

PMID- 23555216
TI  - Probabilistic inference of biochemical reactions in microbial communities from
      metagenomic sequences.
AB  - Shotgun metagenomics has been applied to the studies of the functionality of
      various microbial communities. As a critical analysis step in these studies,
      biological pathways are reconstructed based on the genes predicted from
      metagenomic shotgun sequences. Pathway reconstruction provides insights into the
      functionality of a microbial community and can be used for comparing multiple
      microbial communities. The utilization of pathway reconstruction, however, can be
      jeopardized because of imperfect functional annotation of genes, and ambiguity in
      the assignment of predicted enzymes to biochemical reactions (e.g., some enzymes
      are involved in multiple biochemical reactions). Considering that metabolic
      functions in a microbial community are carried out by many enzymes in a
      collaborative manner, we present a probabilistic sampling approach to profiling
      functional content in a metagenomic dataset, by sampling functions of
      catalytically promiscuous enzymes within the context of the entire metabolic
      network defined by the annotated metagenome. We test our approach on metagenomic
      datasets from environmental and human-associated microbial communities. The
      results show that our approach provides a more accurate representation of the
      metabolic activities encoded in a metagenome, and thus improves the comparative
      analysis of multiple microbial communities. In addition, our approach reports
      likelihood scores of putative reactions, which can be used to identify important
      reactions and metabolic pathways that reflect the environmental adaptation of the
      microbial communities. Source code for sampling metabolic networks is available
      online at http://omics.informatics.indiana.edu/mg/MetaNetSam/.

PMID- 23555217
TI  - Sustained firing of model central auditory neurons yields a discriminative
      spectro-temporal representation for natural sounds.
AB  - The processing characteristics of neurons in the central auditory system are
      directly shaped by and reflect the statistics of natural acoustic environments,
      but the principles that govern the relationship between natural sound ensembles
      and observed responses in neurophysiological studies remain unclear. In
      particular, accumulating evidence suggests the presence of a code based on
      sustained neural firing rates, where central auditory neurons exhibit strong,
      persistent responses to their preferred stimuli. Such a strategy can indicate the
      presence of ongoing sounds, is involved in parsing complex auditory scenes, and
      may play a role in matching neural dynamics to varying time scales in acoustic
      signals. In this paper, we describe a computational framework for exploring the
      influence of a code based on sustained firing rates on the shape of the spectro
      temporal receptive field (STRF), a linear kernel that maps a spectro-temporal
      acoustic stimulus to the instantaneous firing rate of a central auditory neuron.
      We demonstrate the emergence of richly structured STRFs that capture the
      structure of natural sounds over a wide range of timescales, and show how the
      emergent ensembles resemble those commonly reported in physiological studies.
      Furthermore, we compare ensembles that optimize a sustained firing code with one
      that optimizes a sparse code, another widely considered coding strategy, and
      suggest how the resulting population responses are not mutually exclusive.
      Finally, we demonstrate how the emergent ensembles contour the high-energy
      spectro-temporal modulations of natural sounds, forming a discriminative
      representation that captures the full range of modulation statistics that
      characterize natural sound ensembles. These findings have direct implications for
      our understanding of how sensory systems encode the informative components of
      natural stimuli and potentially facilitate multi-sensory integration.

PMID- 23555218
TI  - Angiogenesis: an adaptive dynamic biological patterning problem.
AB  - Formation of functionally adequate vascular networks by angiogenesis presents a
      problem in biological patterning. Generated without predetermined spatial
      patterns, networks must develop hierarchical tree-like structures for efficient
      convective transport over large distances, combined with dense space-filling
      meshes for short diffusion distances to every point in the tissue. Moreover,
      networks must be capable of restructuring in response to changing functional
      demands without interruption of blood flow. Here, theoretical simulations based
      on experimental data are used to demonstrate that this patterning problem can be
      solved through over-abundant stochastic generation of vessels in response to a
      growth factor generated in hypoxic tissue regions, in parallel with refinement by
      structural adaptation and pruning. Essential biological mechanisms for generation
      of adequate and efficient vascular patterns are identified and impairments in
      vascular properties resulting from defects in these mechanisms are predicted. The
      results provide a framework for understanding vascular network formation in
      normal or pathological conditions and for predicting effects of therapies
      targeting angiogenesis.

PMID- 23555219
TI  - Stability and responsiveness in a self-organized living architecture.
AB  - Robustness and adaptability are central to the functioning of biological systems,
      from gene networks to animal societies. Yet the mechanisms by which living
      organisms achieve both stability to perturbations and sensitivity to input are
      poorly understood. Here, we present an integrated study of a living architecture
      in which army ants interconnect their bodies to span gaps. We demonstrate that
      these self-assembled bridges are a highly effective means of maintaining traffic
      flow over unpredictable terrain. The individual-level rules responsible depend
      only on locally-estimated traffic intensity and the number of neighbours to which
      ants are attached within the structure. We employ a parameterized computational
      model to reveal that bridges are tuned to be maximally stable in the face of
      regular, periodic fluctuations in traffic. However analysis of the model also
      suggests that interactions among ants give rise to feedback processes that result
      in bridges being highly responsive to sudden interruptions in traffic. Subsequent
      field experiments confirm this prediction and thus the dual nature of stability
      and flexibility in living bridges. Our study demonstrates the importance of
      robust and adaptive modular architecture to efficient traffic organisation and
      reveals general principles regarding the regulation of form in biological self
      assemblies.

PMID- 23555220
TI  - Neuronal avalanches differ from wakefulness to deep sleep--evidence from
      intracranial depth recordings in humans.
AB  - Neuronal activity differs between wakefulness and sleep states. In contrast, an
      attractor state, called self-organized critical (SOC), was proposed to govern
      brain dynamics because it allows for optimal information coding. But is the human
      brain SOC for each vigilance state despite the variations in neuronal dynamics?
      We characterized neuronal avalanches--spatiotemporal waves of enhanced activity-
      from dense intracranial depth recordings in humans. We showed that avalanche
      distributions closely follow a power law--the hallmark feature of SOC--for each
      vigilance state. However, avalanches clearly differ with vigilance states: slow
      wave sleep (SWS) shows large avalanches, wakefulness intermediate, and rapid eye
      movement (REM) sleep small ones. Our SOC model, together with the data, suggested
      first that the differences are mediated by global but tiny changes in synaptic
      strength, and second, that the changes with vigilance states reflect small
      deviations from criticality to the subcritical regime, implying that the human
      brain does not operate at criticality proper but close to SOC. Independent of
      criticality, the analysis confirms that SWS shows increased correlations between
      cortical areas, and reveals that REM sleep shows more fragmented cortical
      dynamics.

PMID- 23555221
TI  - A circadian clock-regulated toggle switch explains AtGRP7 and AtGRP8 oscillations
      in Arabidopsis thaliana.
AB  - The circadian clock controls many physiological processes in higher plants and
      causes a large fraction of the genome to be expressed with a 24h rhythm. The
      transcripts encoding the RNA-binding proteins AtGRP7 (Arabidopsis thaliana
      Glycine Rich Protein 7) and AtGRP8 oscillate with evening peaks. The circadian
      clock components CCA1 and LHY negatively affect AtGRP7 expression at the level of
      transcription. AtGRP7 and AtGRP8, in turn, negatively auto-regulate and
      reciprocally cross-regulate post-transcriptionally: high protein levels promote
      the generation of an alternative splice form that is rapidly degraded. This clock
      regulated feedback loop has been proposed to act as a molecular slave oscillator
      in clock output. While mathematical models describing the circadian core
      oscillator in Arabidopsis thaliana were introduced recently, we propose here the
      first model of a circadian slave oscillator. We define the slave oscillator in
      terms of ordinary differential equations and identify the model's parameters by
      an optimization procedure based on experimental results. The model successfully
      reproduces the pertinent experimental findings such as waveforms, phases, and
      half-lives of the time-dependent concentrations. Furthermore, we obtain insights
      into possible mechanisms underlying the observed experimental dynamics: the
      negative auto-regulation and reciprocal cross-regulation via alternative splicing
      could be responsible for the sharply peaking waveforms of the AtGRP7 and AtGRP8
      mRNA. Moreover, our results suggest that the AtGRP8 transcript oscillations are
      subordinated to those of AtGRP7 due to a higher impact of AtGRP7 protein on
      alternative splicing of its own and of the AtGRP8 pre-mRNA compared to the impact
      of AtGRP8 protein. Importantly, a bifurcation analysis provides theoretical
      evidence that the slave oscillator could be a toggle switch, arising from the
      reciprocal cross-regulation at the post-transcriptional level. In view of this,
      transcriptional repression of AtGRP7 and AtGRP8 by LHY and CCA1 induces
      oscillations of the toggle switch, leading to the observed high-amplitude
      oscillations of AtGRP7 mRNA.

PMID- 23555222
TI  - Inferring metabolic states in uncharacterized environments using gene-expression
      measurements.
AB  - The large size of metabolic networks entails an overwhelming multiplicity in the
      possible steady-state flux distributions that are compatible with stoichiometric
      constraints. This space of possibilities is largest in the frequent situation
      where the nutrients available to the cells are unknown. These two factors:
      network size and lack of knowledge of nutrient availability, challenge the
      identification of the actual metabolic state of living cells among the myriad
      possibilities. Here we address this challenge by developing a method that
      integrates gene-expression measurements with genome-scale models of metabolism as
      a means of inferring metabolic states. Our method explores the space of
      alternative flux distributions that maximize the agreement between gene
      expression and metabolic fluxes, and thereby identifies reactions that are likely
      to be active in the culture from which the gene-expression measurements were
      taken. These active reactions are used to build environment-specific metabolic
      models and to predict actual metabolic states. We applied our method to model the
      metabolic states of Saccharomyces cerevisiae growing in rich media supplemented
      with either glucose or ethanol as the main energy source. The resulting models
      comprise about 50% of the reactions in the original model, and predict
      environment-specific essential genes with high sensitivity. By minimizing the sum
      of fluxes while forcing our predicted active reactions to carry flux, we
      predicted the metabolic states of these yeast cultures that are in large
      agreement with what is known about yeast physiology. Most notably, our method
      predicts the Crabtree effect in yeast cells growing in excess glucose, a long
      known phenomenon that could not have been predicted by traditional constraint
      based modeling approaches. Our method is of immediate practical relevance for
      medical and industrial applications, such as the identification of novel drug
      targets, and the development of biotechnological processes that use complex,
      largely uncharacterized media, such as biofuel production.

PMID- 23555224
TI  - In-silico assessment of protein-protein electron transfer. a case study:
      cytochrome c peroxidase--cytochrome c.
AB  - The fast development of software and hardware is notably helping in closing the
      gap between macroscopic and microscopic data. Using a novel theoretical strategy
      combining molecular dynamics simulations, conformational clustering, ab-initio
      quantum mechanics and electronic coupling calculations, we show how computational
      methodologies are mature enough to provide accurate atomistic details into the
      mechanism of electron transfer (ET) processes in complex protein systems, known
      to be a significant challenge. We performed a quantitative study of the ET
      between Cytochrome c Peroxidase and its redox partner Cytochrome c. Our results
      confirm the ET mechanism as hole transfer (HT) through residues Ala194, Ala193,
      Gly192 and Trp191 of CcP. Furthermore, our findings indicate the fine evolution
      of the enzyme to approach an elevated turnover rate of 5.47 * 10(6) s(-1) for the
      ET between Cytc and CcP through establishment of a localized bridge state in
      Trp191.

PMID- 23555223
TI  - A multi-scale analysis of influenza A virus fitness trade-offs due to temperature
      dependent virus persistence.
AB  - Successful replication within an infected host and successful transmission
      between hosts are key to the continued spread of most pathogens. Competing
      selection pressures exerted at these different scales can lead to evolutionary
      trade-offs between the determinants of fitness within and between hosts. Here, we
      examine such a trade-off in the context of influenza A viruses and the
      differential pressures exerted by temperature-dependent virus persistence. For a
      panel of avian influenza A virus strains, we find evidence for a trade-off
      between the persistence at high versus low temperatures. Combining a within-host
      model of influenza infection dynamics with a between-host transmission model, we
      study how such a trade-off affects virus fitness on the host population level. We
      show that conclusions regarding overall fitness are affected by the type of link
      assumed between the within- and between-host levels and the main route of
      transmission (direct or environmental). The relative importance of virulence and
      immune response mediated virus clearance are also found to influence the fitness
      impacts of virus persistence at low versus high temperatures. Based on our
      results, we predict that if transmission occurs mainly directly and scales
      linearly with virus load, and virulence or immune responses are negligible, the
      evolutionary pressure for influenza viruses to evolve toward good persistence at
      high within-host temperatures dominates. For all other scenarios, influenza
      viruses with good environmental persistence at low temperatures seem to be
      favored.

PMID- 23555225
TI  - A model of binocular rivalry and cross-orientation suppression.
AB  - Binocular rivalry and cross-orientation suppression are well-studied forms of
      competition in visual cortex, but models of these two types of competition are in
      tension with one another. Binocular rivalry occurs during the presentation of
      dichoptic grating stimuli, where two orthogonal gratings presented separately to
      the two eyes evoke strong alternations in perceptual dominance. Cross-orientation
      suppression occurs during the presentation of plaid stimuli, where the responses
      to a component grating presented to both eyes is weakened by the presence of a
      superimposed orthogonal grating. Conventional models of rivalry that rely on
      strong competition between orientation-selective neurons incorrectly predict
      rivalry between the components of plaids. Lowering the inhibitory weights in such
      models reduces rivalry for plaids, but also reduces it for dichoptic gratings.
      Using an exhaustive grid search, we show that this problem cannot be solved
      simply by adjusting the parameters of the model. Instead, we propose a robust
      class of models that rely on ocular opponency neurons, previously proposed as a
      mechanism for efficient stereo coding, to yield rivalry only for dichoptic
      gratings, not for plaids. This class of models reconciles models of binocular
      rivalry with the divisive normalization framework that has been used to explain
      cross-orientation. Our model makes novel predictions that we confirmed with
      psychophysical tests.

PMID- 23555226
TI  - Under-dominance constrains the evolution of negative autoregulation in diploids.
AB  - Regulatory networks have evolved to allow gene expression to rapidly track
      changes in the environment as well as to buffer perturbations and maintain
      cellular homeostasis in the absence of change. Theoretical work and empirical
      investigation in Escherichia coli have shown that negative autoregulation confers
      both rapid response times and reduced intrinsic noise, which is reflected in the
      fact that almost half of Escherichia coli transcription factors are negatively
      autoregulated. However, negative autoregulation is rare amongst the transcription
      factors of Saccharomyces cerevisiae. This difference is surprising because E.
      coli and S. cerevisiae otherwise have similar profiles of network motifs. In this
      study we investigate regulatory interactions amongst the transcription factors of
      Drosophila melanogaster and humans, and show that they have a similar dearth of
      negative autoregulation to that seen in S. cerevisiae. We then present a model
      demonstrating that this striking difference in the noise reduction strategies
      used amongst species can be explained by constraints on the evolution of negative
      autoregulation in diploids. We show that regulatory interactions between pairs of
      homologous genes within the same cell can lead to under-dominance--mutations
      which result in stronger autoregulation, and decrease noise in homozygotes,
      paradoxically can cause increased noise in heterozygotes. This severely limits a
      diploid's ability to evolve negative autoregulation as a noise reduction
      mechanism. Our work offers a simple and general explanation for a previously
      unexplained difference between the regulatory architectures of E. coli and yeast,
      Drosophila and humans. It also demonstrates that the effects of diploidy in gene
      networks can have counter-intuitive consequences that may profoundly influence
      the course of evolution.

PMID- 23555227
TI  - The fate of cooperation during range expansions.
AB  - Species expand their geographical ranges following an environmental change, long
      range dispersal, or a new adaptation. Range expansions not only bring an
      ecological change, but also affect the evolution of the expanding species.
      Although the dynamics of deleterious, neutral, and beneficial mutations have been
      extensively studied in expanding populations, the fate of alleles under frequency
      dependent selection remains largely unexplored. The dynamics of cooperative
      alleles are particularly interesting because selection can be both frequency and
      density dependent, resulting in a coupling between population and evolutionary
      dynamics. This coupling leads to an increase in the frequency of cooperators at
      the expansion front, and, under certain conditions, the entire front can be taken
      over by cooperators. Thus, a mixed population wave can split into an expansion
      wave of only cooperators followed by an invasion wave of defectors. After the
      splitting, cooperators increase in abundance by expanding into new territories
      faster than they are invaded by defectors. Our results not only provide an
      explanation for the maintenance of cooperation but also elucidate the effect of
      eco-evolutionary feedback on the maintenance of genetic diversity during range
      expansions. When cooperators do not split away, we find that defectors can spread
      much faster with cooperators than they would be able to on their own or by
      invading cooperators. This enhanced rate of expansion in mixed waves could
      counterbalance the loss of genetic diversity due to the founder effect for
      mutations under frequency-dependent selection. Although we focus on cooperator
      defector interactions, our analysis could also be relevant for other systems
      described by reaction-diffusion equations.

PMID- 23555228
TI  - Rampant exchange of the structure and function of extramembrane domains between
      membrane and water soluble proteins.
AB  - Of the membrane proteins of known structure, we found that a remarkable 67% of
      the water soluble domains are structurally similar to water soluble proteins of
      known structure. Moreover, 41% of known water soluble protein structures share a
      domain with an already known membrane protein structure. We also found that
      functional residues are frequently conserved between extramembrane domains of
      membrane and soluble proteins that share structural similarity. These results
      suggest membrane and soluble proteins readily exchange domains and their
      attendant functionalities. The exchanges between membrane and soluble proteins
      are particularly frequent in eukaryotes, indicating that this is an important
      mechanism for increasing functional complexity. The high level of structural
      overlap between the two classes of proteins provides an opportunity to employ the
      extensive information on soluble proteins to illuminate membrane protein
      structure and function, for which much less is known. To this end, we employed
      structure guided sequence alignment to elucidate the functions of membrane
      proteins in the human genome. Our results bridge the gap of fold space between
      membrane and water soluble proteins and provide a resource for the prediction of
      membrane protein function. A database of predicted structural and functional
      relationships for proteins in the human genome is provided at
      sbi.postech.ac.kr/emdmp.

PMID- 23555229
TI  - Systematic prediction of pharmacodynamic drug-drug interactions through protein
      protein-interaction network.
AB  - Identifying drug-drug interactions (DDIs) is a major challenge in drug
      development. Previous attempts have established formal approaches for
      pharmacokinetic (PK) DDIs, but there is not a feasible solution for
      pharmacodynamic (PD) DDIs because the endpoint is often a serious adverse event
      rather than a measurable change in drug concentration. Here, we developed a
      metric "S-score" that measures the strength of network connection between drug
      targets to predict PD DDIs. Utilizing known PD DDIs as golden standard positives
      (GSPs), we observed a significant correlation between S-score and the likelihood
      a PD DDI occurs. Our prediction was robust and surpassed existing methods as
      validated by two independent GSPs. Analysis of clinical side effect data
      suggested that the drugs having predicted DDIs have similar side effects. We
      further incorporated this clinical side effects evidence with S-score to increase
      the prediction specificity and sensitivity through a Bayesian probabilistic
      model. We have predicted 9,626 potential PD DDIs at the accuracy of 82% and the
      recall of 62%. Importantly, our algorithm provided opportunities for better
      understanding the potential molecular mechanisms or physiological effects
      underlying DDIs, as illustrated by the case studies.

PMID- 23555230
TI  - Outlier responses reflect sensitivity to statistical structure in the human
      brain.
AB  - We constantly look for patterns in the environment that allow us to learn its key
      regularities. These regularities are fundamental in enabling us to make
      predictions about what is likely to happen next. The physiological study of
      regularity extraction has focused primarily on repetitive sequence-based rules
      within the sensory environment, or on stimulus-outcome associations in the
      context of reward-based decision-making. Here we ask whether we implicitly encode
      non-sequential stochastic regularities, and detect violations therein. We
      addressed this question using a novel experimental design and both behavioural
      and magnetoencephalographic (MEG) metrics associated with responses to pure-tone
      sounds with frequencies sampled from a Gaussian distribution. We observed that
      sounds in the tail of the distribution evoked a larger response than those that
      fell at the centre. This response resembled the mismatch negativity (MMN) evoked
      by surprising or unlikely events in traditional oddball paradigms. Crucially,
      responses to physically identical outliers were greater when the distribution was
      narrower. These results show that humans implicitly keep track of the uncertainty
      induced by apparently random distributions of sensory events. Source
      reconstruction suggested that the statistical-context-sensitive responses arose
      in a temporo-parietal network, areas that have been associated with attention
      orientation to unexpected events. Our results demonstrate a very early
      neurophysiological marker of the brain's ability to implicitly encode complex
      statistical structure in the environment. We suggest that this sensitivity
      provides a computational basis for our ability to make perceptual inferences in
      noisy environments and to make decisions in an uncertain world.

PMID- 23555231
TI  - Transcriptome profiling of Giardia intestinalis using strand-specific RNA-seq.
AB  - Giardia intestinalis is a common cause of diarrheal disease and it consists of
      eight genetically distinct genotypes or assemblages (A-H). Only assemblages A and
      B infect humans and are suggested to represent two different Giardia species.
      Correlations exist between assemblage type and host-specificity and to some
      extent symptoms. Phenotypical differences have been documented between
      assemblages and genome sequences are available for A, B and E. We have
      characterized and compared the polyadenylated transcriptomes of assemblages A, B
      and E. Four genetically different isolates were studied (WB (AI), AS175 (AII),
      P15 (E) and GS (B)) using paired-end, strand-specific RNA-seq. Most of the genome
      was transcribed in trophozoites grown in vitro, but at vastly different levels.
      RNA-seq confirmed many of the present annotations and refined the current genome
      annotation. Gene expression divergence was found to recapitulate the known
      phylogeny, and uncovered lineage-specific differences in expression.
      Polyadenylation sites were mapped for over 70% of the genes and revealed many
      examples of conserved and unexpectedly long 3' UTRs. 28 open reading frames were
      found in a non-transcribed gene cluster on chromosome 5 of the WB isolate.
      Analysis of allele-specific expression revealed a correlation between allele
      dosage and allele expression in the GS isolate. Previously reported cis-splicing
      events were confirmed and global mapping of cis-splicing identified only one
      novel intron. These observations can possibly explain differences in host
      preference and symptoms, and it will be the basis for further studies of Giardia
      pathogenesis and biology.

PMID- 23555232
TI  - Folding pathways of a knotted protein with a realistic atomistic force field.
AB  - We report on atomistic simulation of the folding of a natively-knotted protein,
      MJ0366, based on a realistic force field. To the best of our knowledge this is
      the first reported effort where a realistic force field is used to investigate
      the folding pathways of a protein with complex native topology. By using the
      dominant-reaction pathway scheme we collected about 30 successful folding
      trajectories for the 82-amino acid long trefoil-knotted protein. Despite the
      dissimilarity of their initial unfolded configuration, these trajectories reach
      the natively-knotted state through a remarkably similar succession of steps. In
      particular it is found that knotting occurs essentially through a threading
      mechanism, involving the passage of the C-terminal through an open region created
      by the formation of the native [Formula: see text]-sheet at an earlier stage. The
      dominance of the knotting by threading mechanism is not observed in MJ0366
      folding simulations using simplified, native-centric models. This points to a
      previously underappreciated role of concerted amino acid interactions, including
      non-native ones, in aiding the appropriate order of contact formation to achieve
      knotting.

PMID- 23555233
TI  - Connecting the kinetics and energy landscape of tRNA translocation on the
      ribosome.
AB  - Functional rearrangements in biomolecular assemblies result from diffusion across
      an underlying energy landscape. While bulk kinetic measurements rely on discrete
      state-like approximations to the energy landscape, single-molecule methods can
      project the free energy onto specific coordinates. With measures of the
      diffusion, one may establish a quantitative bridge between state-like kinetic
      measurements and the continuous energy landscape. We used an all-atom molecular
      dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to
      provide this bridge for specific conformational events associated with the
      process of tRNA translocation. Starting from a pre-translocation configuration,
      we identified sets of residues that collectively undergo rotary rearrangements
      implicated in ribosome function. Estimates of the diffusion coefficients along
      these collective coordinates for translocation were then used to interconvert
      between experimental rates and measures of the energy landscape. This analysis,
      in conjunction with previously reported experimental rates of translocation,
      provides an upper-bound estimate of the free-energy barriers associated with
      translocation. While this analysis was performed for a particular kinetic scheme
      of translocation, the quantitative framework is general and may be applied to
      energetic and kinetic descriptions that include any number of intermediates and
      transition states.

PMID- 23555234
TI  - Systems model of T cell receptor proximal signaling reveals emergent
      ultrasensitivity.
AB  - Receptor phosphorylation is thought to be tightly regulated because
      phosphorylated receptors initiate signaling cascades leading to cellular
      activation. The T cell antigen receptor (TCR) on the surface of T cells is
      phosphorylated by the kinase Lck and dephosphorylated by the phosphatase CD45 on
      multiple immunoreceptor tyrosine-based activation motifs (ITAMs). Intriguingly,
      Lck sequentially phosphorylates ITAMs and ZAP-70, a cytosolic kinase, binds to
      phosphorylated ITAMs with differential affinities. The purpose of multiple ITAMs,
      their sequential phosphorylation, and the differential ZAP-70 affinities are
      unknown. Here, we use a systems model to show that this signaling architecture
      produces emergent ultrasensitivity resulting in switch-like responses at the
      scale of individual TCRs. Importantly, this switch-like response is an emergent
      property, so that removal of multiple ITAMs, sequential phosphorylation, or
      differential affinities abolishes the switch. We propose that highly regulated
      TCR phosphorylation is achieved by an emergent switch-like response and use the
      systems model to design novel chimeric antigen receptors for therapy.

PMID- 23555235
TI  - An integrated computational/experimental model of lymphoma growth.
AB  - Non-Hodgkin's lymphoma is a disseminated, highly malignant cancer, with
      resistance to drug treatment based on molecular- and tissue-scale characteristics
      that are intricately linked. A critical element of molecular resistance has been
      traced to the loss of functionality in proteins such as the tumor suppressor p53.
      We investigate the tissue-scale physiologic effects of this loss by integrating
      in vivo and immunohistological data with computational modeling to study the
      spatiotemporal physical dynamics of lymphoma growth. We compare between drug
      sensitive EMU-myc Arf-/- and drug-resistant EMU-myc p53-/- lymphoma cell tumors
      grown in live mice. Initial values for the model parameters are obtained in part
      by extracting values from the cellular-scale from whole-tumor histological
      staining of the tumor-infiltrated inguinal lymph node in vivo. We compare model
      predicted tumor growth with that observed from intravital microscopy and
      macroscopic imaging in vivo, finding that the model is able to accurately predict
      lymphoma growth. A critical physical mechanism underlying drug-resistant
      phenotypes may be that the EMU-myc p53-/- cells seem to pack more closely within
      the tumor than the EMU-myc Arf-/- cells, thus possibly exacerbating diffusion
      gradients of oxygen, leading to cell quiescence and hence resistance to cell
      cycle specific drugs. Tighter cell packing could also maintain steeper gradients
      of drug and lead to insufficient toxicity. The transport phenomena within the
      lymphoma may thus contribute in nontrivial, complex ways to the difference in
      drug sensitivity between EMU-myc Arf-/- and EMU-myc p53-/- tumors, beyond what
      might be solely expected from loss of functionality at the molecular scale. We
      conclude that computational modeling tightly integrated with experimental data
      gives insight into the dynamics of Non-Hodgkin's lymphoma and provides a platform
      to generate confirmable predictions of tumor growth.

PMID- 23555236
TI  - Origin and evolution of protein fold designs inferred from phylogenomic analysis
      of CATH domain structures in proteomes.
AB  - The spatial arrangements of secondary structures in proteins, irrespective of
      their connectivity, depict the overall shape and organization of protein domains.
      These features have been used in the CATH and SCOP classifications to
      hierarchically partition fold space and define the architectural make up of
      proteins. Here we use phylogenomic methods and a census of CATH structures in
      hundreds of genomes to study the origin and diversification of protein
      architectures (A) and their associated topologies (T) and superfamilies (H).
      Phylogenies that describe the evolution of domain structures and proteomes were
      reconstructed from the structural census and used to generate timelines of domain
      discovery. Phylogenies of CATH domains at T and H levels of structural
      abstraction and associated chronologies revealed patterns of reductive evolution,
      the early rise of Archaea, three epochs in the evolution of the protein world,
      and patterns of structural sharing between superkingdoms. Phylogenies of
      proteomes confirmed the early appearance of Archaea. While these findings are in
      agreement with previous phylogenomic studies based on the SCOP classification,
      phylogenies unveiled sharing patterns between Archaea and Eukarya that are recent
      and can explain the canonical bacterial rooting typically recovered from sequence
      analysis. Phylogenies of CATH domains at A level uncovered general patterns of
      architectural origin and diversification. The tree of A structures showed that
      ancient structural designs such as the 3-layer (alphabetaalpha) sandwich (3.40)
      or the orthogonal bundle (1.10) are comparatively simpler in their makeup and are
      involved in basic cellular functions. In contrast, modern structural designs such
      as prisms, propellers, 2-solenoid, super-roll, clam, trefoil and box are not
      widely distributed and were probably adopted to perform specialized functions.
      Our timelines therefore uncover a universal tendency towards protein structural
      complexity that is remarkable.

PMID- 23555237
TI  - Sparse distributed representation of odors in a large-scale olfactory bulb
      circuit.
AB  - In the olfactory bulb, lateral inhibition mediated by granule cells has been
      suggested to modulate the timing of mitral cell firing, thereby shaping the
      representation of input odorants. Current experimental techniques, however, do
      not enable a clear study of how the mitral-granule cell network sculpts odor
      inputs to represent odor information spatially and temporally. To address this
      critical step in the neural basis of odor recognition, we built a biophysical
      network model of mitral and granule cells, corresponding to 1/100th of the real
      system in the rat, and used direct experimental imaging data of glomeruli
      activated by various odors. The model allows the systematic investigation and
      generation of testable hypotheses of the functional mechanisms underlying odor
      representation in the olfactory bulb circuit. Specifically, we demonstrate that
      lateral inhibition emerges within the olfactory bulb network through recurrent
      dendrodendritic synapses when constrained by a range of balanced excitatory and
      inhibitory conductances. We find that the spatio-temporal dynamics of lateral
      inhibition plays a critical role in building the glomerular-related cell clusters
      observed in experiments, through the modulation of synaptic weights during odor
      training. Lateral inhibition also mediates the development of sparse and
      synchronized spiking patterns of mitral cells related to odor inputs within the
      network, with the frequency of these synchronized spiking patterns also modulated
      by the sniff cycle.

PMID- 23555238
TI  - Colocalization of coregulated genes: a steered molecular dynamics study of human
      chromosome 19.
AB  - The connection between chromatin nuclear organization and gene activity is
      vividly illustrated by the observation that transcriptional coregulation of
      certain genes appears to be directly influenced by their spatial proximity. This
      fact poses the more general question of whether it is at all feasible that the
      numerous genes that are coregulated on a given chromosome, especially those at
      large genomic distances, might become proximate inside the nucleus. This problem
      is studied here using steered molecular dynamics simulations in order to enforce
      the colocalization of thousands of knowledge-based gene sequences on a model for
      the gene-rich human chromosome 19. Remarkably, it is found that most (~ 88%) gene
      pairs can be brought simultaneously into contact. This is made possible by the
      low degree of intra-chromosome entanglement and the large number of cliques in
      the gene coregulatory network. A clique is a set of genes coregulated all
      together as a group. The constrained conformations for the model chromosome 19
      are further shown to be organized in spatial macrodomains that are similar to
      those inferred from recent HiC measurements. The findings indicate that gene
      coregulation and colocalization are largely compatible and that this relationship
      can be exploited to draft the overall spatial organization of the chromosome in
      vivo. The more general validity and implications of these findings could be
      investigated by applying to other eukaryotic chromosomes the general and
      transferable computational strategy introduced here.

PMID- 23555239
TI  - Generators of phenotypic diversity in the evolution of pathogenic microorganisms.

PMID- 23555240
TI  - The KdpD/KdpE two-component system: integrating K+ homeostasis and virulence.
AB  - The two-component system (TCS) KdpD/KdpE, extensively studied for its regulatory
      role in potassium (K(+)) transport, has more recently been identified as an
      adaptive regulator involved in the virulence and intracellular survival of
      pathogenic bacteria, including Staphylococcus aureus, entero-haemorrhagic
      Escherichia coli, Salmonella typhimurium, Yersinia pestis, Francisella species,
      Photorhabdus asymbiotica, and mycobacteria. Key homeostasis requirements
      monitored by KdpD/KdpE and other TCSs such as PhoP/PhoQ are critical to survival
      in the stressful conditions encountered by pathogens during host interactions. It
      follows these TCSs may therefore acquire adaptive roles in response to selective
      pressures associated with adopting a pathogenic lifestyle. Given the central role
      of K(+) in virulence, we propose that KdpD/KdpE, as a regulator of a high
      affinity K(+) pump, has evolved virulence-related regulatory functions. In
      support of this hypothesis, we review the role of KdpD/KdpE in bacterial
      infection and summarize evidence that (i) KdpD/KdpE production is correlated with
      enhanced virulence and survival, (ii) KdpE regulates a range of virulence loci
      through direct promoter binding, and (iii) KdpD/KdpE regulation responds to
      virulence-related conditions including phagocytosis, exposure to microbicides,
      quorum sensing signals, and host hormones. Furthermore, antimicrobial stress,
      osmotic stress, and oxidative stress are associated with KdpD/KdpE activity, and
      the system's accessory components (which allow TCS fine-tuning or crosstalk)
      provide links to stress response pathways. KdpD/KdpE therefore appears to be an
      important adaptive TCS employed during host infection, promoting bacterial
      virulence and survival through mechanisms both related to and distinct from its
      conserved role in K(+) regulation.

PMID- 23555241
TI  - Redefining the immune system as a social interface for cooperative processes.

PMID- 23555243
TI  - Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non
      canonical death receptor interactions.
AB  - The TRAIL (TNF-related apoptosis inducing ligand) death receptors (DRs) of the
      tumor necrosis factor receptor superfamily (TNFRSF) can promote apoptosis and
      regulate antiviral immunity by maintaining immune homeostasis during infection.
      In turn, human cytomegalovirus (HCMV) expresses immunomodulatory proteins that
      down-regulate cell surface expression of TNFRSF members as well as poliovirus
      receptor-related proteins in an effort to inhibit host immune effector pathways
      that would lead to viral clearance. The UL141 glycoprotein of human
      cytomegalovirus inhibits host defenses by blocking cell surface expression of
      TRAIL DRs (by retention in ER) and poliovirus receptor CD155, a nectin-like Ig
      fold molecule. Here we show that the immunomodulatory function of HCMV UL141 is
      associated with its ability to bind diverse proteins, while utilizing at least
      two distinct binding sites to selectively engage TRAIL DRs or CD155. Binding
      studies revealed high affinity interaction of UL141 with both TRAIL-R2 and CD155
      and low affinity binding to TRAIL-R1. We determined the crystal structure of
      UL141 bound to TRAIL-R2 at 2.1 A resolution, which revealed that UL141 forms a
      homodimer that engages two TRAIL-R2 monomers 90 degrees  apart to form a
      heterotetrameric complex. Our structural and biochemical data reveal that UL141
      utilizes its Ig-domain to facilitate non-canonical death receptor interactions
      while UL141 partially mimics the binding site of TRAIL on TRAIL-R2, which we
      found to be distinct from that of CD155. Moreover, UL141 also binds to an
      additional surface patch on TRAIL-R2 that is distinct from the TRAIL binding
      site. Therefore, the breadth of UL141-mediated effects indicates that HCMV has
      evolved sophisticated strategies to evade the immune system by modulating
      multiple effector pathways.

PMID- 23555242
TI  - Biomphalysin, a new beta pore-forming toxin involved in Biomphalaria glabrata
      immune defense against Schistosoma mansoni.
AB  - Aerolysins are virulence factors belonging to the beta pore-forming toxin (beta
      PFT) superfamily that are abundantly distributed in bacteria. More rarely, beta
      PFTs have been described in eukaryotic organisms. Recently, we identified a
      putative cytolytic protein in the snail, Biomphalaria glabrata, whose primary
      structural features suggest that it could belong to this beta-PFT superfamily. In
      the present paper, we report the molecular cloning and functional
      characterization of this protein, which we call Biomphalysin, and demonstrate
      that it is indeed a new eukaryotic beta-PFT. We show that, despite weak sequence
      similarities with aerolysins, Biomphalysin shares a common architecture with
      proteins belonging to this superfamily. A phylogenetic approach revealed that the
      gene encoding Biomphalysin could have resulted from horizontal transfer. Its
      expression is restricted to immune-competent cells and is not induced by parasite
      challenge. Recombinant Biomphalysin showed hemolytic activity that was greatly
      enhanced by the plasma compartment of B. glabrata. We further demonstrated that
      Biomphalysin with plasma is highly toxic toward Schistosoma mansoni sporocysts.
      Using in vitro binding assays in conjunction with Western blot and
      immunocytochemistry analyses, we also showed that Biomphalysin binds to parasite
      membranes. Finally, we showed that, in contrast to what has been reported for
      most other members of the family, lytic activity of Biomphalysin is not dependent
      on proteolytic processing. These results provide the first functional description
      of a mollusk immune effector protein involved in killing S. mansoni.

PMID- 23555244
TI  - HSV-2 specifically down regulates HLA-C expression to render HSV-2-infected DCs
      susceptible to NK cell killing.
AB  - Both NK cells and CTLs kill virus-infected and tumor cells. However, the ways by
      which these killer cells recognize the infected or the tumorigenic cells are
      different, in fact almost opposite. CTLs are activated through the interaction of
      the TCR with MHC class I proteins. In contrast, NK cells are inhibited by MHC
      class I molecules. The inhibitory NK receptors recognize mainly MHC class I
      proteins and in this regard practically all of the HLA-C proteins are recognized
      by inhibitory NK cell receptors, while only certain HLA-A and HLA-B proteins
      interact with these receptors. Sophisticated viruses developed mechanisms to
      avoid the attack of both NK cells and CTLs through, for example, down regulation
      of HLA-A and HLA-B molecules to avoid CTL recognition, leaving HLA-C proteins on
      the cell surface to inhibit NK cell response. Here we provide the first example
      of a virus that through specific down regulation of HLA-C, harness the NK cells
      for its own benefit. We initially demonstrated that none of the tested HSV-2
      derived microRNAs affect NK cell activity. Then we show that surprisingly upon
      HSV-2 infection, HLA-C proteins are specifically down regulated, rendering the
      infected cells susceptible to NK cell attack. We identified a motif in the tail
      of HLA-C that is responsible for the HSV-2-meduiated HLA-C down regulation and we
      show that the HLA-C down regulation is mediated by the viral protein ICP47.
      Finally we show that HLA-C proteins are down regulated from the surface of HSV-2
      infected dendritic cells (DCs) and that this leads to the killing of DC by NK
      cells. Thus, we propose that HSV-2 had developed this unique and surprising NK
      cell-mediated killing strategy of infected DC to prevent the activation of the
      adaptive immunity.

PMID- 23555245
TI  - Productive homologous and non-homologous recombination of hepatitis C virus in
      cell culture.
AB  - Genetic recombination is an important mechanism for increasing diversity of RNA
      viruses, and constitutes a viral escape mechanism to host immune responses and to
      treatment with antiviral compounds. Although rare, epidemiologically important
      hepatitis C virus (HCV) recombinants have been reported. In addition,
      recombination is an important regulatory mechanism of cytopathogenicity for the
      related pestiviruses. Here we describe recombination of HCV RNA in cell culture
      leading to production of infectious virus. Initially, hepatoma cells were co
      transfected with a replicating JFH1DeltaE1E2 genome (genotype 2a) lacking
      functional envelope genes and strain J6 (2a), which has functional envelope genes
      but does not replicate in culture. After an initial decrease in the number of HCV
      positive cells, infection spread after 13-36 days. Sequencing of recovered
      viruses revealed non-homologous recombinants with J6 sequence from the 5' end to
      the NS2-NS3 region followed by JFH1 sequence from Core to the 3' end. These
      recombinants carried duplicated sequence of up to 2400 nucleotides. HCV
      replication was not required for recombination, as recombinants were observed in
      most experiments even when two replication incompetent genomes were co
      transfected. Reverse genetic studies verified the viability of representative
      recombinants. After serial passage, subsequent recombination events reducing or
      eliminating the duplicated region were observed for some but not all
      recombinants. Furthermore, we found that inter-genotypic recombination could
      occur, but at a lower frequency than intra-genotypic recombination. Productive
      recombination of attenuated HCV genomes depended on expression of all HCV
      proteins and tolerated duplicated sequence. In general, no strong site
      specificity was observed. Non-homologous recombination was observed in most
      cases, while few homologous events were identified. A better understanding of HCV
      recombination could help identification of natural recombinants and thereby lead
      to improved therapy. Our findings suggest mechanisms for occurrence of
      recombinants observed in patients.

PMID- 23555246
TI  - Plasminogen controls inflammation and pathogenesis of influenza virus infections
      via fibrinolysis.
AB  - Detrimental inflammation of the lungs is a hallmark of severe influenza virus
      infections. Endothelial cells are the source of cytokine amplification, although
      mechanisms underlying this process are unknown. Here, using combined
      pharmacological and gene-deletion approaches, we show that plasminogen controls
      lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly
      pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication
      was not responsible for the observed effect. However, pharmacological depletion
      of fibrinogen, the main target of plasminogen reversed disease resistance of
      plasminogen-deficient mice or mice treated with an inhibitor of plasminogen
      mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious
      inflammation of the lungs and local fibrin clot formation may be implicated in
      host defense against influenza virus infections. Our studies suggest that the
      hemostatic system might be explored for novel treatments against influenza.

PMID- 23555247
TI  - Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I
      interferon responses.
AB  - Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth
      disease (HFMD). Its pathogenicity is not fully understood, but innate immune
      evasion is likely a key factor. Strategies to circumvent the initiation and
      effector phases of anti-viral innate immunity are well known; less well known is
      whether EV71 evades the signal transduction phase regulated by a sophisticated
      interplay of cellular and viral proteins. Here, we show that EV71 inhibits anti
      viral type I interferon (IFN) responses by targeting the mitochondrial anti-viral
      signaling (MAVS) protein--a unique adaptor molecule activated upon retinoic acid
      induced gene-I (RIG-I) and melanoma differentiation associated gene (MDA-5) viral
      recognition receptor signaling--upstream of type I interferon production. MAVS
      was cleaved and released from mitochondria during EV71 infection. An in vitro
      cleavage assay demonstrated that the viral 2A protease (2A(pro)), but not the
      mutant 2A(pro) (2A(pro)-110) containing an inactivated catalytic site, cleaved
      MAVS. The Protease-Glo assay revealed that MAVS was cleaved at 3 residues between
      the proline-rich and transmembrane domains, and the resulting fragmentation
      effectively inactivated downstream signaling. In addition to MAVS cleavage, we
      found that EV71 infection also induced morphologic and functional changes to the
      mitochondria. The EV71 structural protein VP1 was detected on purified
      mitochondria, suggesting not only a novel role for mitochondria in the EV71
      replication cycle but also an explanation of how EV71-derived 2A(pro) could
      approach MAVS. Taken together, our findings reveal a novel strategy employed by
      EV71 to escape host anti-viral innate immunity that complements the known EV71
      mediated immune-evasion mechanisms.

PMID- 23555248
TI  - TIM-family proteins promote infection of multiple enveloped viruses through
      virion-associated phosphatidylserine.
AB  - Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4)
      specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a
      cellular receptor for hepatitis A virus and Ebola virus and as an entry factor
      for dengue virus. Here we show that TIM1 promotes infection of retroviruses and
      virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in
      particular those from the filovirus, flavivirus, New World arenavirus and
      alphavirus families. TIM1 also robustly enhanced the infection of replication
      competent viruses from the same families, including dengue, Tacaribe, Sindbis and
      Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were
      PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis
      experiments. In addition, other PS-binding proteins, such as Axl and TIM4,
      promoted infection similarly to TIM1. Finally, the blocking of PS receptors on
      macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can
      contribute to infection in physiologically relevant cells. Notably, infection
      mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS
      coronavirus was largely unaffected by TIM1 expression. Taken together our data
      show that TIM1 and related PS-binding proteins promote infection of diverse
      families of enveloped viruses, and may therefore be useful targets for broad
      spectrum antiviral therapies.

PMID- 23555249
TI  - Lymphotoxin signaling is initiated by the viral polymerase in HCV-linked
      tumorigenesis.
AB  - Exposure to hepatitis C virus (HCV) typically results in chronic infection that
      leads to progressive liver disease ranging from mild inflammation to severe
      fibrosis and cirrhosis as well as primary liver cancer. HCV triggers innate
      immune signaling within the infected hepatocyte, a first step in mounting of the
      adaptive response against HCV infection. Persistent inflammation is strongly
      associated with liver tumorigenesis. The goal of our work was to investigate the
      initiation of the inflammatory processes triggered by HCV viral proteins in their
      host cell and their possible link with HCV-related liver cancer. We report a
      dramatic upregulation of the lymphotoxin signaling pathway and more specifically
      of lymphotoxin-beta in tumors of the FL-N/35 HCV-transgenic mice. Lymphotoxin
      expression is accompanied by activation of NF-kappaB, neosynthesis of chemokines
      and intra-tumoral recruitment of mononuclear cells. Spectacularly, IKKbeta
      inactivation in FL-N/35 mice drastically reduces tumor incidence. Activation of
      lymphotoxin-beta pathway can be reproduced in several cellular models, including
      the full length replicon and HCV-infected primary human hepatocytes. We have
      identified NS5B, the HCV RNA dependent RNA polymerase, as the viral protein
      responsible for this phenotype and shown that pharmacological inhibition of its
      activity alleviates activation of the pro-inflammatory pathway. These results
      open new perspectives in understanding the inflammatory mechanisms linked to HCV
      infection and tumorigenesis.

PMID- 23555250
TI  - Prophage induction is enhanced and required for renal disease and lethality in an
      EHEC mouse model.
AB  - Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes
      hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies
      showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by
      EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial
      subpopulation in which the 933W prophage is induced is the producer of Stx2.
      Using the germ-free mouse, we show the essential role 933W induction plays in the
      virulence of EDL933 infection. An EDL933 derivative with a single mutation in its
      933W prophage, resulting specifically in that phage being uninducible, colonizes
      the intestines, but fails to cause any of the pathological changes seen with the
      parent strain. Hence, induction of the 933W prophage is the primary event leading
      to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET,
      with a biosensor that specifically measures induction of the 933W prophage. Using
      this biosensor to measure 933W induction in germ-free mice, we found an increase
      three logs greater than was expected from in vitro results. Since the induced
      population produces and releases Stx2, this result indicates that an activity in
      the intestine increases Stx2 production.

PMID- 23555251
TI  - Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae.
AB  - Secondary bacterial infections are a leading cause of illness and death during
      epidemic and pandemic influenza. Experimental studies suggest a lethal synergism
      between influenza and certain bacteria, particularly Streptococcus pneumoniae,
      but the precise processes involved are unclear. To address the mechanisms and
      determine the influences of pathogen dose and strain on disease, we infected
      groups of mice with either the H1N1 subtype influenza A virus A/Puerto Rico/8/34
      (PR8) or a version expressing the 1918 PB1-F2 protein (PR8-PB1-F2(1918)),
      followed seven days later with one of two S. pneumoniae strains, type 2 D39 or
      type 3 A66.1. We determined that, following bacterial infection, viral titers
      initially rebound and then decline slowly. Bacterial titers rapidly rise to high
      levels and remain elevated. We used a kinetic model to explore the coupled
      interactions and study the dominant controlling mechanisms. We hypothesize that
      viral titers rebound in the presence of bacteria due to enhanced viral release
      from infected cells, and that bacterial titers increase due to alveolar
      macrophage impairment. Dynamics are affected by initial bacterial dose but not by
      the expression of the influenza 1918 PB1-F2 protein. Our model provides a
      framework to investigate pathogen interaction during coinfections and to uncover
      dynamical differences based on inoculum size and strain.

PMID- 23555252
TI  - A36-dependent actin filament nucleation promotes release of vaccinia virus.
AB  - Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions
      that remain attached to the outer surface of the cell or those released into the
      medium. During egress, the outer membrane of the double-enveloped virus fuses
      with the plasma membrane leaving extracellular virus attached to the cell surface
      via viral envelope proteins. Here we report that F-actin nucleation by the viral
      protein A36 promotes the disengagement of virus attachment and release of
      enveloped virus. Cells infected with the A36(YdF) virus, which has mutations at
      two critical tyrosine residues abrogating localised actin nucleation, displayed a
      10-fold reduction in virus release. We examined A36(YdF) infected cells by
      transmission electron microscopy and observed that during release, virus appeared
      trapped in small invaginations at the plasma membrane. To further characterise
      the mechanism by which actin nucleation drives the dissociation of enveloped
      virus from the cell surface, we examined recombinant viruses by super-resolution
      microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to
      image cell-virus attachment in mutant and parental backgrounds. We confirmed that
      A36(YdF) extracellular virus remained closely associated to the plasma membrane
      in small membrane pits. Virus-induced actin nucleation reduced the extent of
      association, thereby promoting the untethering of virus from the cell surface.
      Virus release can be enhanced via a point mutation in the luminal region of B5
      (P189S), another virus envelope protein. We found that the B5(P189S) mutation led
      to reduced contact between extracellular virus and the host membrane during
      release, even in the absence of virus-induced actin nucleation. Our results posit
      that during release virus is tightly tethered to the host cell through
      interactions mediated by viral envelope proteins. Untethering of virus into the
      surrounding extracellular space requires these interactions be relieved, either
      through the force of actin nucleation or by mutations in luminal proteins that
      weaken these interactions.

PMID- 23555253
TI  - The enterovirus 71 A-particle forms a gateway to allow genome release: a cryoEM
      study of picornavirus uncoating.
AB  - Since its discovery in 1969, enterovirus 71 (EV71) has emerged as a serious
      worldwide health threat. This human pathogen of the picornavirus family causes
      hand, foot, and mouth disease, and also has the capacity to invade the central
      nervous system to cause severe disease and death. Upon binding to a host receptor
      on the cell surface, the virus begins a two-step uncoating process, first forming
      an expanded, altered "A-particle", which is primed for genome release. In a
      second step after endocytosis, an unknown trigger leads to RNA expulsion,
      generating an intact, empty capsid. Cryo-electron microscopy reconstructions of
      these two capsid states provide insight into the mechanics of genome release. The
      EV71 A-particle capsid interacts with the genome near the icosahedral two-fold
      axis of symmetry, which opens to the external environment via a channel ~10 A in
      diameter that is lined with patches of negatively charged residues. After the
      EV71 genome has been released, the two-fold channel shrinks, though the overall
      capsid dimensions are conserved. These structural characteristics identify the
      two-fold channel as the site where a gateway forms and regulates the process of
      genome release.

PMID- 23555254
TI  - Digoxin suppresses HIV-1 replication by altering viral RNA processing.
AB  - To develop new approaches to control HIV-1 replication, we examined the capacity
      of recently described small molecular modulators of RNA splicing for their
      effects on viral RNA metabolism. Of the drugs tested, digoxin was found to induce
      a dramatic inhibition of HIV-1 structural protein synthesis, a response due, in
      part, to reduced accumulation of the corresponding viral mRNAs. In addition,
      digoxin altered viral RNA splice site use, resulting in loss of the essential
      viral factor Rev. Digoxin induced changes in activity of the CLK family of SR
      protein kinases and modification of several SR proteins, including SRp20 and
      Tra2beta, which could account for the effects observed. Consistent with this
      hypothesis, overexpression of SRp20 elicited changes in HIV-1 RNA processing
      similar to those observed with digoxin. Importantly, digoxin was also highly
      active against clinical strains of HIV-1 in vitro, validating this novel approach
      to treatment of this infection.

PMID- 23555255
TI  - HIV restriction by APOBEC3 in humanized mice.
AB  - Innate immune restriction factors represent important specialized barriers to
      zoonotic transmission of viruses. Significant consideration has been given to
      their possible use for therapeutic benefit. The apolipoprotein B mRNA editing
      enzyme catalytic polypeptide 3 (APOBEC3) family of cytidine deaminases are potent
      immune defense molecules capable of efficiently restricting endogenous
      retroelements as well as a broad range of viruses including Human
      Immunodeficiency virus (HIV), Hepatitis B virus (HBV), Human Papilloma virus
      (HPV), and Human T Cell Leukemia virus (HTLV). The best characterized members of
      this family are APOBEC3G (A3G) and APOBEC3F (A3F) and their restriction of HIV.
      HIV has evolved to counteract these powerful restriction factors by encoding an
      accessory gene designated viral infectivity factor (vif). Here we demonstrate
      that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif.
      However, our results also show that CXCR4-tropic HIV can escape from APOBEC3
      restriction and replicate in vivo independent of Vif. Molecular analysis
      identified thymocytes as cells with reduced A3G and A3F expression. Direct
      injection of vif-defective HIV into the thymus resulted in viral replication and
      dissemination detected by plasma viral load analysis; however, vif-defective
      viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation
      was observed in proviral DNA recovered from other organs. Remarkably, HIV
      replication persisted despite the inability of HIV to develop resistance to
      APOBEC3 in the absence of Vif. Our results provide novel insight into a highly
      specific subset of cells that potentially circumvent the action of APOBEC3;
      however our results also demonstrate the massive inactivation of CCR5-tropic HIV
      in the absence of Vif.

PMID- 23555256
TI  - IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major
      infection.
AB  - Leishmaniasis, resulting from infection with the protozoan parasite Leishmania,
      consists of a wide spectrum of clinical manifestations, from healing cutaneous
      lesions to fatal visceral infections. A particularly severe form of cutaneous
      leishmaniasis, termed mucosal leishmaniasis, exhibits decreased IL-10 levels and
      an exaggerated inflammatory response that perpetuates the disease. Using a mouse
      model of leishmaniasis, we investigated what cytokines contribute to increased
      pathology when IL-10-mediated regulation is absent. Leishmania major infected
      C57BL/6 mice lacking IL-10 regulation developed larger lesions than controls, but
      fewer parasites. Both IFN-gamma and IL-17 levels were substantially elevated in
      mice lacking the capacity to respond to IL-10. IFN-gamma promoted an increased
      infiltration of monocytes, while IL-17 contributed to an increase in neutrophils.
      Surprisingly, however, we found that IFN-gamma did not contribute to increased
      pathology, but instead regulated the IL-17 response. Thus, blocking IFN-gamma led
      to a significant increase in IL-17, neutrophils and disease. Similarly, the
      production of IL-17 by cells from leishmaniasis patients was also regulated by IL
      10 and IFN-gamma. Additional studies found that the IL-1 receptor was required
      for both the IL-17 response and increased pathology. Therefore, we propose that
      regulating IL-17, possibly by downregulating IL-1beta, may be a useful approach
      for controlling immunopathology in leishmaniasis.

PMID- 23555257
TI  - Temporal analysis of hepatitis C virus cell entry with occludin directed blocking
      antibodies.
AB  - Hepatitis C virus (HCV) is a major cause of liver disease worldwide. A better
      understanding of its life cycle, including the process of host cell entry, is
      important for the development of HCV therapies and model systems. Based on the
      requirement for numerous host factors, including the two tight junction proteins
      claudin-1 (CLDN1) and occludin (OCLN), HCV cell entry has been proposed to be a
      multi-step process. The lack of OCLN-specific inhibitors has prevented a
      comprehensive analysis of this process. To study the role of OCLN in HCV cell
      entry, we created OCLN mutants whose HCV cell entry activities could be inhibited
      by antibodies. These mutants were expressed in polarized HepG2 cells engineered
      to support the complete HCV life cycle by CD81 and miR-122 expression and
      synchronized infection assays were performed to define the kinetics of HCV cell
      entry. During these studies, OCLN utilization differences between HCV isolates
      were observed, supporting a model that HCV directly interacts with OCLN. In HepG2
      cells, both HCV cell entry and tight junction formation were impaired by OCLN
      silencing and restored by expression of antibody regulatable OCLN mutant.
      Synchronized infection assays showed that glycosaminoglycans and SR-BI mediated
      host cell binding, while CD81, CLDN1 and OCLN all acted sequentially at a post
      binding stage prior to endosomal acidification. These results fit a model where
      the tight junction region is the last to be encountered by the virion prior to
      internalization.

PMID- 23555258
TI  - The common structural architecture of Shigella flexneri and Salmonella
      typhimurium type three secretion needles.
AB  - The Type Three Secretion System (T3SS), or injectisome, is a macromolecular
      infection machinery present in many pathogenic Gram-negative bacteria. It
      consists of a basal body, anchored in both bacterial membranes, and a hollow
      needle through which effector proteins are delivered into the target host cell.
      Two different architectures of the T3SS needle have been previously proposed.
      First, an atomic model of the Salmonella typhimurium needle was generated from
      solid-state NMR data. The needle subunit protein, PrgI, comprises a rigid
      extended N-terminal segment and a helix-loop-helix motif with the N-terminus
      located on the outside face of the needle. Second, a model of the Shigella
      flexneri needle was generated from a high-resolution 7.7-A cryo-electron
      microscopy density map. The subunit protein, MxiH, contains an N-terminal alpha
      helix, a loop, another alpha-helix, a 14-residue-long beta-hairpin (Q51-Q64) and
      a C-terminal alpha-helix, with the N-terminus facing inward to the lumen of the
      needle. In the current study, we carried out solid-state NMR measurements of wild
      type Shigella flexneri needles polymerized in vitro and identified the following
      secondary structure elements for MxiH: a rigid-extended N-terminal segment (S2
      T11), an alpha-helix (L12-A38), a loop (E39-P44) and a C-terminal alpha-helix
      (Q45-R83). Using immunogold labeling in vitro and in vivo on functional needles,
      we located the N-terminus of MxiH subunits on the exterior of the assembly,
      consistent with evolutionary sequence conservation patterns and mutagenesis data.
      We generated a homology model of Shigella flexneri needles compatible with both
      experimental data: the MxiH solid-state NMR chemical shifts and the state-of-the
      art cryoEM density map. These results corroborate the solid-state NMR structure
      previously solved for Salmonella typhimurium PrgI needles and establish that
      Shigella flexneri and Salmonella typhimurium subunit proteins adopt a conserved
      structure and orientation in their assembled state. Our study reveals a common
      structural architecture of T3SS needles, essential to understand T3SS-mediated
      infection and develop treatments.

PMID- 23555259
TI  - Dimeric RNA recognition regulates HIV-1 genome packaging.
AB  - How retroviruses regulate the amount of RNA genome packaged into each virion has
      remained a long-standing question. Our previous study showed that most HIV-1
      particles contain two copies of viral RNA, indicating that the number of genomes
      packaged is tightly regulated. In this report, we examine the mechanism that
      controls the number of RNA genomes encapsidated into HIV-1 particles. We
      hypothesize that HIV-1 regulates genome packaging by either the mass or copy
      number of the viral RNA. These two distinct mechanisms predict different outcomes
      when the genome size deviates significantly from that of wild type. Regulation by
      RNA mass would result in multiple copies of a small genome or one copy of a large
      genome being packaged, whereas regulation by copy number would result in two
      copies of a genome being packaged independent of size. To distinguish between
      these two hypotheses, we examined the packaging of viral RNA that was larger (~17
      kb) or smaller (~3 kb) than that of wild-type HIV-1 (~9 kb) and found that most
      particles packaged two copies of the viral genome regardless of whether they were
      17 kb or 3 kb. Therefore, HIV-1 regulates RNA genome encapsidation not by the
      mass of RNA but by packaging two copies of RNA. To further explore the mechanism
      that governs this regulation, we examined the packaging of viral RNAs containing
      two packaging signals that can form intermolecular dimers or intramolecular
      dimers (self-dimers) and found that one self-dimer is packaged. Therefore, HIV-1
      recognizes one dimeric RNA instead of two copies of RNA. Our findings reveal that
      dimeric RNA recognition is the key mechanism that regulates HIV-1 genome
      encapsidation and provide insights into a critical step in the generation of
      infectious viruses.

PMID- 23555260
TI  - Two-component signal transduction system CBO0787/CBO0786 represses transcription
      from botulinum neurotoxin promoters in Clostridium botulinum ATCC 3502.
AB  - Blocking neurotransmission, botulinum neurotoxin is the most poisonous biological
      substance known to mankind. Despite its infamy as the scourge of the food
      industry, the neurotoxin is increasingly used as a pharmaceutical to treat an
      expanding range of muscle disorders. Whilst neurotoxin expression by the spore
      forming bacterium Clostridium botulinum appears tightly regulated, to date only
      positive regulatory elements, such as the alternative sigma factor BotR, have
      been implicated in this control. The identification of negative regulators has
      proven to be elusive. Here, we show that the two-component signal transduction
      system CBO0787/CBO0786 negatively regulates botulinum neurotoxin expression.
      Single insertional inactivation of cbo0787 encoding a sensor histidine kinase, or
      of cbo0786 encoding a response regulator, resulted in significantly elevated
      neurotoxin gene expression levels and increased neurotoxin production.
      Recombinant CBO0786 regulator was shown to bind to the conserved -10 site of the
      core promoters of the ha and ntnh-botA operons, which encode the toxin structural
      and accessory proteins. Increasing concentration of CBO0786 inhibited BotR
      directed transcription from the ha and ntnh-botA promoters, demonstrating direct
      transcriptional repression of the ha and ntnh-botA operons by CBO0786. Thus, we
      propose that CBO0786 represses neurotoxin gene expression by blocking BotR
      directed transcription from the neurotoxin promoters. This is the first evidence
      of a negative regulator controlling botulinum neurotoxin production.
      Understanding the neurotoxin regulatory mechanisms is a major target of the food
      and pharmaceutical industries alike.

PMID- 23555261
TI  - TIM-3 does not act as a receptor for galectin-9.
AB  - T cell immunoglobulin and mucin protein 3 (TIM-3) is a type I cell surface
      protein that was originally identified as a marker for murine T helper type 1
      cells. TIM-3 was found to negatively regulate murine T cell responses and
      galectin-9 was described as a binding partner that mediates T cell inhibitory
      effects of TIM-3. Moreover, it was reported that like PD-1 the classical
      exhaustion marker, TIM-3 is up-regulated in exhausted murine and human T cells
      and TIM-3 blockade was described to restore the function of these T cells. Here
      we show that the activation of human T cells is not affected by the presence of
      galectin-9 or antibodies to TIM-3. Furthermore, extensive studies on the
      interaction of galectin-9 with human and murine TIM-3 did not yield evidence for
      specific binding between these molecules. Moreover, profound differences were
      observed when analysing the expression of TIM-3 and PD-1 on T cells of HIV-1
      infected individuals: TIM-3 was expressed on fewer cells and also at much lower
      levels. Furthermore, whereas PD-1 was preferentially expressed on CD45RA(-)CD8 T
      cells, the majority of TIM-3-expressing CD8 T cells were CD45RA(+). Importantly,
      we found that TIM-3 antibodies were ineffective in increasing anti-HIV-1 T cell
      responses in vitro, whereas PD-L antibodies potently reverted the dysfunctional
      state of exhausted CD8 T cells. Taken together, our results are not in support of
      an interaction between TIM-3 and galectin-9 and yield no evidence for a
      functional role of TIM-3 in human T cell activation. Moreover, our data indicate
      that PD-1, but not TIM-3, is a promising target to ameliorate T cell exhaustion.

PMID- 23555262
TI  - Transcriptional responses of in vivo praziquantel exposure in schistosomes
      identifies a functional role for calcium signalling pathway member CamKII.
AB  - Treatment for clinical schistosomiasis has relied centrally on the broad spectrum
      anthelmintic praziquantel; however, there is limited information on its mode of
      action or the molecular response of the parasite. This paper presents a
      transcriptional and functional approach to defining the molecular responses of
      schistosomes to praziquantel. Differential gene expression in Schistosoma
      japonicum was investigated by transcriptome-wide microarray analysis of adult
      worms perfused from infected mice after 0.5 to 24 hours after oral administration
      of sub-lethal doses of praziquantel. Genes up-regulated initially in male
      parasites were associated with "Tegument/Muscle Repair" and "Lipid/Ion
      Regulation" functions and were followed by "Drug Resistance" and "Ion Regulation"
      associated genes. Prominent responses induced in female worms included up
      regulation of "Ca(2+) Regulation" and "Drug Resistance" genes and later by
      transcripts of "Detoxification" and "Pathogen Defense" mechanisms. A subset of
      highly over-expressed genes, with putative drug resistance/detoxification roles
      or Ca(2+)-dependant/modulatory functions, were validated by qPCR. The leading
      candidate among these was CamKII, a putative calcium/calmodulin-dependent protein
      kinase type II delta chain. RNA interference was employed to knockdown CamKII in
      S. japonicum to determine the role of CamKII in the response to praziquantel.
      After partial-knockdown, schistosomes were analysed using IC50 concentrations
      (50% worm motility) and quantitative monitoring of parasite movement. When CamKII
      transcription was reduced by 50-69% in S. japonicum, the subsequent effect of an
      IC50 dosage of praziquantel was exacerbated, reducing motility from 47% to 27% in
      female worms and from 61% to 23% in males. These observations indicated that
      CamKII mitigates the effects of praziquantel, probably through stabilising Ca(2+)
      fluxes within parasite muscles and tegument. Together, these studies
      comprehensively charted transcriptional changes upon exposure to praziquantel
      and, notably, identified CamKII as potentially central to the, as yet undefined,
      mode of action of praziquantel.

PMID- 23555263
TI  - Dendritic cell-induced activation of latent HIV-1 provirus in actively
      proliferating primary T lymphocytes.
AB  - HIV-1 latency remains a formidable barrier towards virus eradication as
      therapeutic attempts to purge these reservoirs are so far unsuccessful. The pool
      of transcriptionally silent proviruses is established early in infection and
      persists for a lifetime, even when viral loads are suppressed below detection
      levels using anti-retroviral therapy. Upon therapy interruption the reservoir can
      re-establish systemic infection. Different cellular reservoirs that harbor latent
      provirus have been described. In this study we demonstrate that HIV-1 can also
      establish a silent integration in actively proliferating primary T lymphocytes.
      Co-culturing of these proliferating T lymphocytes with dendritic cells (DCs)
      activated the provirus from latency. Activation did not involve DC-mediated C
      type lectin DC-SIGN signaling or TCR-stimulation but was mediated by DC-secreted
      component(s) and cell-cell interaction between DC and T lymphocyte that could be
      inhibited by blocking ICAM-1 dependent adhesion. These results imply that
      circulating DCs could purge HIV-1 from latency and re-initiate virus replication.
      Moreover, our data show that viral latency can be established early after
      infection and supports the idea that actively proliferating T lymphocytes with an
      effector phenotype contribute to the latent viral reservoir. Unraveling this
      physiologically relevant purging mechanism could provide useful information for
      the development of new therapeutic strategies that aim at the eradication of HIV
      1 reservoirs.

PMID- 23555264
TI  - DNA break site at fragile subtelomeres determines probability and mechanism of
      antigenic variation in African trypanosomes.
AB  - Antigenic variation in African trypanosomes requires monoallelic transcription
      and switching of variant surface glycoprotein (VSG) genes. The transcribed VSG,
      always flanked by '70 bp'-repeats and telomeric-repeats, is either replaced
      through DNA double-strand break (DSB) repair or transcriptionally inactivated.
      However, little is known about the subtelomeric DSBs that naturally trigger
      antigenic variation in Trypanosoma brucei, the subsequent DNA damage responses,
      or how these responses determine the mechanism of VSG switching. We found that
      DSBs naturally accumulate close to both transcribed and non-transcribed
      telomeres. We then induced high-efficiency meganuclease-mediated DSBs and
      monitored DSB-responses and DSB-survivors. By inducing breaks at distinct sites
      within both transcribed and silent VSG transcription units and assessing local
      DNA resection, histone modification, G2/M-checkpoint activation, and both RAD51
      dependent and independent repair, we reveal how breaks at different sites trigger
      distinct responses and, in 'active-site' survivors, different switching
      mechanisms. At the active site, we find that promoter-adjacent breaks typically
      failed to trigger switching, 70 bp-repeat-adjacent breaks almost always triggered
      switching through 70 bp-repeat recombination (~60% RAD51-dependent), and telomere
      repeat-adjacent breaks triggered switching through loss of the VSG expression
      site (25% of survivors). Expression site loss was associated with G2/M-checkpoint
      bypass, while 70 bp-repeat-recombination was associated with DNA-resection,
      gammaH2A-focus assembly and a G2/M-checkpoint. Thus, the probability and
      mechanism of antigenic switching are highly dependent upon the location of the
      break. We conclude that 70 bp-repeat-adjacent and telomere-repeat-adjacent breaks
      trigger distinct checkpoint responses and VSG switching pathways. Our results
      show how subtelomere fragility can generate the triggers for the major antigenic
      variation mechanisms in the African trypanosome.

PMID- 23555265
TI  - Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon
      signaling.
AB  - An estimated 50 million dengue virus (DENV) infections occur annually and more
      than forty percent of the human population is currently at risk of developing
      dengue fever (DF) or dengue hemorrhagic fever (DHF). Despite the prevalence and
      potential severity of DF and DHF, there are no approved vaccines or antiviral
      therapeutics available. An improved understanding of DENV immune evasion is
      pivotal for the rational development of anti-DENV therapeutics. Antagonism of
      type I interferon (IFN-I) signaling is a crucial mechanism of DENV immune
      evasion. DENV NS5 protein inhibits IFN-I signaling by mediating proteasome
      dependent STAT2 degradation. Only proteolytically-processed NS5 can efficiently
      mediate STAT2 degradation, though both unprocessed and processed NS5 bind STAT2.
      Here we identify UBR4, a 600-kDa member of the N-recognin family, as an
      interacting partner of DENV NS5 that preferentially binds to processed NS5. Our
      results also demonstrate that DENV NS5 bridges STAT2 and UBR4. Furthermore, we
      show that UBR4 promotes DENV-mediated STAT2 degradation, and most importantly,
      that UBR4 is necessary for efficient viral replication in IFN-I competent cells.
      Our data underscore the importance of NS5-mediated STAT2 degradation in DENV
      replication and identify UBR4 as a host protein that is specifically exploited by
      DENV to inhibit IFN-I signaling via STAT2 degradation.

PMID- 23555266
TI  - Genome-wide determinants of proviral targeting, clonal abundance and expression
      in natural HTLV-1 infection.
AB  - The regulation of proviral latency is a central problem in retrovirology. We
      postulate that the genomic integration site of human T lymphotropic virus type 1
      (HTLV-1) determines the pattern of expression of the provirus, which in turn
      determines the abundance and pathogenic potential of infected T cell clones in
      vivo. We recently developed a high-throughput method for the genome-wide
      amplification, identification and quantification of proviral integration sites.
      Here, we used this protocol to test two hypotheses. First, that binding sites for
      transcription factors and chromatin remodelling factors in the genome flanking
      the proviral integration site of HTLV-1 are associated with integration
      targeting, spontaneous proviral expression, and in vivo clonal abundance. Second,
      that the transcriptional orientation of the HTLV-1 provirus relative to that of
      the nearest host gene determines spontaneous proviral expression and in vivo
      clonal abundance. Integration targeting was strongly associated with the presence
      of a binding site for specific host transcription factors, especially STAT1 and
      p53. The presence of the chromatin remodelling factors BRG1 and INI1 and certain
      host transcription factors either upstream or downstream of the provirus was
      associated respectively with silencing or spontaneous expression of the provirus.
      Cells expressing HTLV-1 Tax protein were significantly more frequent in clones of
      low abundance in vivo. We conclude that transcriptional interference and
      chromatin remodelling are critical determinants of proviral latency in natural
      HTLV-1 infection.

PMID- 23555267
TI  - Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated
      apoptosis.
AB  - Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus
      cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome
      (HPS)), both human diseases with high case-fatality rates. Endothelial cells are
      the main targets for hantaviruses. An intriguing observation in patients with
      HFRS and HCPS is that on one hand the virus infection leads to strong activation
      of CD8 T cells and NK cells, on the other hand no obvious destruction of infected
      endothelial cells is observed. Here, we provide an explanation for this dichotomy
      by showing that hantavirus-infected endothelial cells are protected from
      cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential
      mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid
      protein inhibits the enzymatic activity of both granzyme B and caspase 3. This
      provides a tentative explanation for the hantavirus-mediated block of cytotoxic
      granule-mediated apoptosis-induction, and hence the protection of infected cells
      from cytotoxic lymphocytes. These findings may explain why infected endothelial
      cells in hantavirus-infected patients are not destroyed by the strong cytotoxic
      lymphocyte response.

PMID- 23555268
TI  - A ubiquitin-specific protease possesses a decisive role for adenovirus
      replication and oncogene-mediated transformation.
AB  - Adenoviral replication depends on viral as well as cellular proteins. However,
      little is known about cellular proteins promoting adenoviral replication. In our
      screens to identify such proteins, we discovered a cellular component of the
      ubiquitin proteasome pathway interacting with the central regulator of adenoviral
      replication. Our binding assays mapped a specific interaction between the N
      terminal domains of both viral E1B-55K and USP7, a deubiquitinating enzyme. RNA
      interference-mediated downregulation of USP7 severely reduced E1B-55K protein
      levels, but more importantly negatively affected adenoviral replication. We also
      succeeded in resynthesizing an inhibitor of USP7, which like the knockdown
      background reduced adenoviral replication. Further assays revealed that not only
      adenoviral growth, but also adenoviral oncogene-driven cellular transformation
      relies on the functions of USP7. Our data provide insights into an intricate
      mechanistic pathway usurped by an adenovirus to promote its replication and
      oncogenic functions, and at the same time open up possibilities for new antiviral
      strategies.

PMID- 23555269
TI  - Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence
      of the lung.
AB  - Pneumococcal carriage is both immunising and a pre-requisite for mucosal and
      systemic disease. Murine models of pneumococcal colonisation show that IL-17A
      secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci
      from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4(+) T-cells
      have not been described in the adult human lung and it is unknown whether they
      can be elicited by carriage and protect the lung from pneumococcal infection. We
      investigated the direct effect of experimental human pneumococcal nasal carriage
      (EHPC) on the frequency and phenotype of cognate CD4(+) T-cells in broncho
      alveolar lavage and blood using multi-parameter flow cytometry. We then examined
      whether they could augment ex vivo alveolar macrophage killing of pneumococci
      using an in vitro assay. We showed that human pneumococcal carriage leads to a
      17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate
      IL-17A(+) CD4(+) T-cells in BAL and blood, respectively. The phenotype with the
      largest proportion were TNF(+)/IL-17A(+) co-producing CD4(+) memory T-cells
      (p<0.01); IFNgamma(+) CD4(+) memory T-cells were not significantly increased
      following carriage. Pneumococci could stimulate large amounts of IL-17A protein
      from BAL cells in the absence of carriage but in the presence of cognate CD4(+)
      memory T-cells, IL-17A protein levels were increased by a further 50%. Further to
      this we then show that alveolar macrophages, which express IL-17A receptors A and
      C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A
      (p = 0.013). Killing negatively correlated with RC (r = -0.9, p = 0.017) but not
      RA expression. We conclude that human pneumococcal carriage can increase the
      proportion of lung IL-17A-secreting CD4(+) memory T-cells that may enhance innate
      cellular immunity against pathogenic challenge. These pathways may be utilised to
      enhance vaccine efficacy to protect the lung against pneumonia.

PMID- 23555270
TI  - Monomeric nucleoprotein of influenza A virus.
AB  - Isolated influenza A virus nucleoprotein exists in an equilibrium between
      monomers and trimers. Samples containing only monomers or only trimers can be
      stabilized by respectively low and high salt. The trimers bind RNA with high
      affinity but remain trimmers, whereas the monomers polymerise onto RNA forming
      nucleoprotein-RNA complexes. When wild type (wt) nucleoprotein is crystallized,
      it forms trimers, whether one starts with monomers or trimers. We therefore
      crystallized the obligate monomeric R416A mutant nucleoprotein and observed how
      the domain exchange loop that leads over to a neighbouring protomer in the trimer
      structure interacts with equivalent sites on the mutant monomer surface, avoiding
      polymerisation. The C-terminus of the monomer is bound to the side of the RNA
      binding surface, lowering its positive charge. Biophysical characterization of
      the mutant and wild type monomeric proteins gives the same results, suggesting
      that the exchange domain is folded in the same way for the wild type protein. In
      a search for how monomeric wt nucleoprotein may be stabilized in the infected
      cell we determined the phosphorylation sites on nucleoprotein isolated from virus
      particles. We found that serine 165 was phosphorylated and conserved in all
      influenza A and B viruses. The S165D mutant that mimics phosphorylation is
      monomeric and displays a lowered affinity for RNA compared with wt monomeric NP.
      This suggests that phosphorylation may regulate the polymerisation state and RNA
      binding of nucleoprotein in the infected cell. The monomer structure could be
      used for finding new anti influenza drugs because compounds that stabilize the
      monomer may slow down viral infection.

PMID- 23555271
TI  - Pandemic influenza A viruses escape from restriction by human MxA through
      adaptive mutations in the nucleoprotein.
AB  - The interferon-induced dynamin-like MxA GTPase restricts the replication of
      influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP)
      of pandemic strains A/Brevig Mission/1/1918 (1918) and A/Hamburg/4/2009 (pH1N1)
      that confer MxA resistance. These resistance-associated amino acids in NP differ
      between the two strains but form a similar discrete surface-exposed cluster in
      the body domain of NP, indicating that MxA resistance evolved independently. The
      1918 cluster was conserved in all descendent strains of seasonal influenza
      viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza
      virus A/Thailand/1(KAN-1)/04 (H5N1) resulted in a gain of MxA resistance coupled
      with a decrease in viral replication fitness. Conversely, introduction of MxA
      sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells.
      We conclude that human MxA represents a barrier against zoonotic introduction of
      avian influenza viruses and that adaptive mutations in the viral NP should be
      carefully monitored.

PMID- 23555272
TI  - Pseudomonas syringae pv. syringae uses proteasome inhibitor syringolin A to
      colonize from wound infection sites.
AB  - Infection of plants by bacterial leaf pathogens at wound sites is common in
      nature. Plants defend wound sites to prevent pathogen invasion, but several
      pathogens can overcome spatial restriction and enter leaf tissues. The molecular
      mechanisms used by pathogens to suppress containment at wound infection sites are
      poorly understood. Here, we studied Pseudomonas syringae strains causing brown
      spot on bean and blossom blight on pear. These strains exist as epiphytes that
      can cause disease upon wounding caused by hail, sand storms and frost. We
      demonstrate that these strains overcome spatial restriction at wound sites by
      producing syringolin A (SylA), a small molecule proteasome inhibitor.
      Consequently, SylA-producing strains are able to escape from primary infection
      sites and colonize adjacent tissues along the vasculature. We found that SylA
      diffuses from the primary infection site and suppresses acquired resistance in
      adjacent tissues by blocking signaling by the stress hormone salicylic acid (SA).
      Thus, SylA diffusion creates a zone of SA-insensitive tissue that is prepared for
      subsequent colonization. In addition, SylA promotes bacterial motility and
      suppresses immune responses at the primary infection site. These local immune
      responses do not affect bacterial growth and were weak compared to effector
      triggered immunity. Thus, SylA facilitates colonization from wounding sites by
      increasing bacterial motility and suppressing SA signaling in adjacent tissues.

PMID- 23555273
TI  - Hepatitis C virus induces the mitochondrial translocation of Parkin and
      subsequent mitophagy.
AB  - Hepatitis C Virus (HCV) induces intracellular events that trigger mitochondrial
      dysfunction and promote host metabolic alterations. Here, we investigated
      selective autophagic degradation of mitochondria (mitophagy) in HCV-infected
      cells. HCV infection stimulated Parkin and PINK1 gene expression, induced
      perinuclear clustering of mitochondria, and promoted mitochondrial translocation
      of Parkin, an initial event in mitophagy. Liver tissues from chronic HCV patients
      also exhibited notable levels of Parkin induction. Using multiple strategies
      involving confocal and electron microscopy, we demonstrated that HCV-infected
      cells display greater number of mitophagosomes and mitophagolysosomes compared to
      uninfected cells. HCV-induced mitophagy was evidenced by the colocalization of
      LC3 puncta with Parkin-associated mitochondria and lysosomes. Ultrastructural
      analysis by electron microscopy and immunoelectron microscopy also displayed
      engulfment of damaged mitochondria in double membrane vesicles in HCV-infected
      cells. The HCV-induced mitophagy occurred irrespective of genotypic differences.
      Silencing Parkin and PINK1 hindered HCV replication suggesting the functional
      relevance of mitophagy in HCV propagation. HCV-mediated decline of mitochondrial
      complex I enzyme activity was rescued by chemical inhibition of mitophagy or by
      Parkin silencing. Overall our results suggest that HCV induces Parkin-dependent
      mitophagy, which may have significant contribution in mitochondrial liver injury
      associated with chronic hepatitis C.

PMID- 23555274
TI  - Power and predictive accuracy of polygenic risk scores.
AB  - Polygenic scores have recently been used to summarise genetic effects among an
      ensemble of markers that do not individually achieve significance in a large
      scale association study. Markers are selected using an initial training sample
      and used to construct a score in an independent replication sample by forming the
      weighted sum of associated alleles within each subject. Association between a
      trait and this composite score implies that a genetic signal is present among the
      selected markers, and the score can then be used for prediction of individual
      trait values. This approach has been used to obtain evidence of a genetic effect
      when no single markers are significant, to establish a common genetic basis for
      related disorders, and to construct risk prediction models. In some cases,
      however, the desired association or prediction has not been achieved. Here, the
      power and predictive accuracy of a polygenic score are derived from a
      quantitative genetics model as a function of the sizes of the two samples,
      explained genetic variance, selection thresholds for including a marker in the
      score, and methods for weighting effect sizes in the score. Expressions are
      derived for quantitative and discrete traits, the latter allowing for
      case/control sampling. A novel approach to estimating the variance explained by a
      marker panel is also proposed. It is shown that published studies with
      significant association of polygenic scores have been well powered, whereas those
      with negative results can be explained by low sample size. It is also shown that
      useful levels of prediction may only be approached when predictors are estimated
      from very large samples, up to an order of magnitude greater than currently
      available. Therefore, polygenic scores currently have more utility for
      association testing than predicting complex traits, but prediction will become
      more feasible as sample sizes continue to grow.

PMID- 23555276
TI  - A novel mutation in the upstream open reading frame of the CDKN1B gene causes a
      MEN4 phenotype.
AB  - The CDKN1B gene encodes the cyclin-dependent kinase inhibitor p27(KIP1), an
      atypical tumor suppressor playing a key role in cell cycle regulation, cell
      proliferation, and differentiation. Impaired p27(KIP1) expression and/or
      localization are often observed in tumor cells, further confirming its central
      role in regulating the cell cycle. Recently, germline mutations in CDKN1B have
      been associated with the inherited multiple endocrine neoplasia syndrome type 4,
      an autosomal dominant syndrome characterized by varying combinations of tumors
      affecting at least two endocrine organs. In this study we identified a 4-bp
      deletion in a highly conserved regulatory upstream ORF (uORF) in the 5'UTR of the
      CDKN1B gene in a patient with a pituitary adenoma and a well-differentiated
      pancreatic neoplasm. This deletion causes the shift of the uORF termination codon
      with the consequent lengthening of the uORF-encoded peptide and the drastic
      shortening of the intercistronic space. Our data on the immunohistochemical
      analysis of the patient's pancreatic lesion, functional studies based on dual
      luciferase assays, site-directed mutagenesis, and on polysome profiling show a
      negative influence of this deletion on the translation reinitiation at the CDKN1B
      starting site, with a consequent reduction in p27(KIP1) expression. Our findings
      demonstrate that, in addition to the previously described mechanisms leading to
      reduced p27(KIP1) activity, such as degradation via the ubiquitin/proteasome
      pathway or non-covalent sequestration, p27(KIP1) activity can also be modulated
      by an uORF and mutations affecting uORF could change p27(KIP1) expression. This
      study adds the CDKN1B gene to the short list of genes for which mutations that
      either create, delete, or severely modify their regulatory uORFs have been
      associated with human diseases.

PMID- 23555275
TI  - Human spermatogenic failure purges deleterious mutation load from the autosomes
      and both sex chromosomes, including the gene DMRT1.
AB  - Gonadal failure, along with early pregnancy loss and perinatal death, may be an
      important filter that limits the propagation of harmful mutations in the human
      population. We hypothesized that men with spermatogenic impairment, a disease
      with unknown genetic architecture and a common cause of male infertility, are
      enriched for rare deleterious mutations compared to men with normal
      spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men
      with idiopathic spermatogenic impairment and more than 1,100 controls, we
      estimate that each rare autosomal deletion detected in our study multiplicatively
      changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], p<2 * 10(-3)), rare
      X-linked CNVs by 29%, (OR 1.29 [1.11-1.50], p<1 * 10(-3)), and rare Y-linked
      duplications by 88% (OR 1.88 [1.13-3.13], p<0.03). By contrasting the properties
      of our case-specific CNVs with those of CNV callsets from cases of autism,
      schizophrenia, bipolar disorder, and intellectual disability, we propose that the
      CNV burden in spermatogenic impairment is distinct from the burden of large,
      dominant mutations described for neurodevelopmental disorders. We identified two
      patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the
      putative sex determination locus of the avian ZW chromosome system. In an
      independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in
      979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in
      an additional 4,519 controls from public databases. The combined results indicate
      that DMRT1 loss-of-function mutations are a risk factor and potential genetic
      cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in
      7,754 controls, p = 6.2 * 10(-5)). Our study identifies other recurrent CNVs as
      potential causes of idiopathic azoospermia and generates hypotheses for directing
      future studies on the genetic basis of male infertility and IVF outcomes.

PMID- 23555277
TI  - Spreading of a prion domain from cell-to-cell by vesicular transport in
      Caenorhabditis elegans.
AB  - Prion proteins can adopt self-propagating alternative conformations that account
      for the infectious nature of transmissible spongiform encephalopathies (TSEs) and
      the epigenetic inheritance of certain traits in yeast. Recent evidence suggests a
      similar propagation of misfolded proteins in the spreading of pathology of
      neurodegenerative diseases including Alzheimer's or Parkinson's disease.
      Currently there is only a limited number of animal model systems available to
      study the mechanisms that underlie the cell-to-cell transmission of aggregation
      prone proteins. Here, we have established a new metazoan model in Caenorhabditis
      elegans expressing the prion domain NM of the cytosolic yeast prion protein
      Sup35, in which aggregation and toxicity are dependent upon the length of
      oligopeptide repeats in the glutamine/asparagine (Q/N)-rich N-terminus. NM forms
      multiple classes of highly toxic aggregate species and co-localizes to autophagy
      related vesicles that transport the prion domain from the site of expression to
      adjacent tissues. This is associated with a profound cell autonomous and cell non
      autonomous disruption of mitochondrial integrity, embryonic and larval arrest,
      developmental delay, widespread tissue defects, and loss of organismal
      proteostasis. Our results reveal that the Sup35 prion domain exhibits prion-like
      properties when expressed in the multicellular organism C. elegans and adapts to
      different requirements for propagation that involve the autophagy-lysosome
      pathway to transmit cytosolic aggregation-prone proteins between tissues.

PMID- 23555278
TI  - Nodule inception directly targets NF-Y subunit genes to regulate essential
      processes of root nodule development in Lotus japonicus.
AB  - The interactions of legumes with symbiotic nitrogen-fixing bacteria cause the
      formation of specialized lateral root organs called root nodules. It has been
      postulated that this root nodule symbiosis system has recruited factors that act
      in early signaling pathways (common SYM genes) partly from the ancestral
      mycorrhizal symbiosis. However, the origins of factors needed for root nodule
      organogenesis are largely unknown. NODULE INCEPTION (NIN) is a nodulation
      specific gene that encodes a putative transcription factor and acts downstream of
      the common SYM genes. Here, we identified two Nuclear Factor-Y (NF-Y) subunit
      genes, LjNF-YA1 and LjNF-YB1, as transcriptional targets of NIN in Lotus
      japonicus. These genes are expressed in root nodule primordia and their
      translational products interact in plant cells, indicating that they form an NF-Y
      complex in root nodule primordia. The knockdown of LjNF-YA1 inhibited root nodule
      organogenesis, as did the loss of function of NIN. Furthermore, we found that NIN
      overexpression induced root nodule primordium-like structures that originated
      from cortical cells in the absence of bacterial symbionts. Thus, NIN is a crucial
      factor responsible for initiating nodulation-specific symbiotic processes. In
      addition, ectopic expression of either NIN or the NF-Y subunit genes caused
      abnormal cell division during lateral root development. This indicated that the
      Lotus NF-Y subunits can function to stimulate cell division. Thus,
      transcriptional regulation by NIN, including the activation of the NF-Y subunit
      genes, induces cortical cell division, which is an initial step in root nodule
      organogenesis. Unlike the legume-specific NIN protein, NF-Y is a major CCAAT box
      binding protein complex that is widespread among eukaryotes. We propose that the
      evolution of root nodules in legume plants was associated with changes in the
      function of NIN. NIN has acquired functions that allow it to divert pathways
      involved in the regulation of cell division to root nodule organogenesis.

PMID- 23555279
TI  - The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in
      Caenorhabditis elegans.
AB  - The Nrf family of transcription factors plays a critical role in mediating
      adaptive responses to cellular stress and defends against neurodegeneration,
      aging, and cancer. Here, we report a novel role for the Caenorhabditis elegans
      Nrf homolog SKN-1 in regulating synaptic transmission at neuromuscular junctions
      (NMJs). Activation of SKN-1, either by acute pharmacological treatment with the
      mitochondrial toxin sodium arsenite or by mutations that cause constitutive SKN-1
      activation, results in defects in neuromuscular function. Additionally,
      elimination of the conserved WD40 repeat protein WDR-23, a principal negative
      regulator of SKN-1, results in impaired locomotion and synaptic vesicle and
      neuropeptide release from cholinergic motor axons. Mutations that abolish skn-1
      activity restore normal neuromuscular function to wdr-23 mutants and animals
      treated with toxin. We show that negative regulation of SKN-1 by WDR-23 in the
      intestine, but not at neuromuscular junctions, is necessary and sufficient for
      proper neuromuscular function. WDR-23 isoforms differentially localize to the
      outer membranes of mitochondria and to nuclei, and the effects of WDR-23 on
      neuromuscular function are dependent on its interaction with cullin E3 ubiquitin
      ligase. Finally, whole-transcriptome RNA sequencing of wdr-23 mutants reveals an
      increase in the expression of known SKN-1/Nrf2-regulated stress-response genes,
      as well as neurotransmission genes not previously implicated in SKN-1/Nrf2
      responses. Together, our results indicate that SKN-1/Nrf2 activation may be a
      mechanism through which cellular stress, detected in one tissue, affects cellular
      function of a distal tissue through endocrine signaling. These results provide
      insight into how SKN-1/Nrf2 might protect the nervous system from damage in
      response to oxidative stress.

PMID- 23555280
TI  - Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue
      comparisons for gene discovery.
AB  - Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously
      replenish the cellular components of the peripheral blood. Observing that the
      ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we
      examined its role in HSC function through in vitro and in vivo assays. Mice
      lacking Atxn1L had greater numbers of HSCs that regenerated the blood more
      quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L
      null HSCs had gene expression changes that regulate a program consistent with
      their higher level of proliferation, suggesting that Atxn1L is a novel regulator
      of HSC quiescence. To determine if additional brain-associated genes were
      candidates for hematologic regulation, we examined genes encoding proteins from
      autism- and ataxia-associated protein-protein interaction networks for their
      representation in hematopoietic cell populations. The interactomes were found to
      be highly enriched for proteins encoded by genes specifically expressed in HSCs
      relative to their differentiated progeny. Our data suggest a heretofore
      unappreciated similarity between regulatory modules in the brain and HSCs,
      offering a new strategy for novel gene discovery in both systems.

PMID- 23555281
TI  - Astakine 2--the dark knight linking melatonin to circadian regulation in
      crustaceans.
AB  - Daily, circadian rhythms influence essentially all living organisms and affect
      many physiological processes from sleep and nutrition to immunity. This ability
      to respond to environmental daily rhythms has been conserved along evolution, and
      it is found among species from bacteria to mammals. The hematopoietic process of
      the crayfish Pacifastacus leniusculus is under circadian control and is tightly
      regulated by astakines, a new family of cytokines sharing a prokineticin (PROK)
      domain. The expression of AST1 and AST2 are light-dependent, and this suggests an
      evolutionarily conserved function for PROK domain proteins in mediating circadian
      rhythms. Vertebrate PROKs are transmitters of circadian rhythms of the
      suprachiasmatic nucleus (SCN) in the brain of mammals, but the mechanism by which
      they function is unknown. Here we demonstrate that high AST2 expression is
      induced by melatonin in the brain. We identify RACK1 as a binding protein of AST2
      and further provide evidence that a complex between AST2 and RACK1 functions as a
      negative-feedback regulator of the circadian clock. By DNA mobility shift assay,
      we showed that the AST2-RACK1 complex will interfere with the binding between
      BMAL1 and CLK and inhibit the E-box binding activity of the complex BMAL1-CLK.
      Finally, we demonstrate by gene knockdown that AST2 is necessary for melatonin
      induced inhibition of the complex formation between BMAL1 and CLK during the dark
      period. In summary, we provide evidence that melatonin regulates AST2 expression
      and thereby affects the core clock of the crustacean brain. This process may be
      very important in all animals that have AST2 molecules, i.e. spiders, ticks,
      crustaceans, scorpions, several insect groups such as Hymenoptera, Hemiptera, and
      Blattodea, but not Diptera and Coleoptera. Our findings further reveal an ancient
      evolutionary role for the prokineticin superfamily protein that links melatonin
      to direct regulation of the core clock gene feedback loops.

PMID- 23555282
TI  - Fine characterisation of a recombination hotspot at the DPY19L2 locus and
      resolution of the paradoxical excess of duplications over deletions in the
      general population.
AB  - We demonstrated previously that 75% of infertile men with round, acrosomeless
      spermatozoa (globozoospermia) had a homozygous 200-Kb deletion removing the
      totality of DPY19L2. We showed that this deletion occurred by Non-Allelic
      Homologous Recombination (NAHR) between two homologous 28-Kb Low Copy Repeats
      (LCRs) located on each side of the gene. The accepted NAHR model predicts that
      inter-chromatid and inter-chromosome NAHR create a deleted and a duplicated
      recombined allele, while intra-chromatid events only generate deletions.
      Therefore more deletions are expected to be produced de novo. Surprisingly, array
      CGH data show that, in the general population, DPY19L2 duplicated alleles are
      approximately three times as frequent as deleted alleles. In order to shed light
      on this paradox, we developed a sperm-based assay to measure the de novo rates of
      deletions and duplications at this locus. As predicted by the NAHR model, we
      identified an excess of de novo deletions over duplications. We calculated that
      the excess of de novo deletion was compensated by evolutionary loss, whereas
      duplications, not subjected to selection, increased gradually. Purifying
      selection against sterile, homozygous deleted men may be sufficient for this
      compensation, but heterozygously deleted men might also suffer a small fitness
      penalty. The recombined alleles were sequenced to pinpoint the localisation of
      the breakpoints. We analysed a total of 15 homozygous deleted patients and 17
      heterozygous individuals carrying either a deletion (n = 4) or a duplication (n =
      13). All but two alleles fell within a 1.2-Kb region central to the 28-Kb LCR,
      indicating that >90% of the NAHR took place in that region. We showed that a
      PRDM9 13-mer recognition sequence is located right in the centre of that region.
      Our results therefore strengthen the link between this consensus sequence and the
      occurrence of NAHR.

PMID- 23555283
TI  - Recurrent rearrangement during adaptive evolution in an interspecific yeast
      hybrid suggests a model for rapid introgression.
AB  - Genome rearrangements are associated with eukaryotic evolutionary processes
      ranging from tumorigenesis to speciation. Rearrangements are especially common
      following interspecific hybridization, and some of these could be expected to
      have strong selective value. To test this expectation we created de novo
      interspecific yeast hybrids between two diverged but largely syntenic
      Saccharomyces species, S. cerevisiae and S. uvarum, then experimentally evolved
      them under continuous ammonium limitation. We discovered that a characteristic
      interspecific genome rearrangement arose multiple times in independently evolved
      populations. We uncovered nine different breakpoints, all occurring in a narrow
      ~1-kb region of chromosome 14, and all producing an "interspecific fusion
      junction" within the MEP2 gene coding sequence, such that the 5' portion derives
      from S. cerevisiae and the 3' portion derives from S. uvarum. In most cases the
      rearrangements altered both chromosomes, resulting in what can be considered to
      be an introgression of a several-kb region of S. uvarum into an otherwise intact
      S. cerevisiae chromosome 14, while the homeologous S. uvarum chromosome 14
      experienced an interspecific reciprocal translocation at the same breakpoint
      within MEP2, yielding a chimaeric chromosome; these events result in the presence
      in the cell of two MEP2 fusion genes having identical breakpoints. Given that
      MEP2 encodes for a high-affinity ammonium permease, that MEP2 fusion genes arise
      repeatedly under ammonium-limitation, and that three independent evolved isolates
      carrying MEP2 fusion genes are each more fit than their common ancestor, the
      novel MEP2 fusion genes are very likely adaptive under ammonium limitation. Our
      results suggest that, when homoploid hybrids form, the admixture of two genomes
      enables swift and otherwise unavailable evolutionary innovations. Furthermore,
      the architecture of the MEP2 rearrangement suggests a model for rapid
      introgression, a phenomenon seen in numerous eukaryotic phyla, that does not
      require repeated backcrossing to one of the parental species.

PMID- 23555284
TI  - A novel role for the RNA-binding protein FXR1P in myoblasts cell-cycle
      progression by modulating p21/Cdkn1a/Cip1/Waf1 mRNA stability.
AB  - The Fragile X-Related 1 gene (FXR1) is a paralog of the Fragile X Mental
      Retardation 1 gene (FMR1), whose absence causes the Fragile X syndrome, the most
      common form of inherited intellectual disability. FXR1P plays an important role
      in normal muscle development, and its absence causes muscular abnormalities in
      mice, frog, and zebrafish. Seven alternatively spliced FXR1 transcripts have been
      identified and two of them are skeletal muscle-specific. A reduction of these
      isoforms is found in myoblasts from Facio-Scapulo Humeral Dystrophy (FSHD)
      patients. FXR1P is an RNA-binding protein involved in translational control;
      however, so far, no mRNA target of FXR1P has been linked to the drastic muscular
      phenotypes caused by its absence. In this study, gene expression profiling of
      C2C12 myoblasts reveals that transcripts involved in cell cycle and muscular
      development pathways are modulated by Fxr1-depletion. We observed an increase of
      p21--a regulator of cell-cycle progression--in Fxr1-knocked-down mouse C2C12 and
      FSHD human myoblasts. Rescue of this molecular phenotype is possible by re
      expressing human FXR1P in Fxr1-depleted C2C12 cells. FXR1P muscle-specific
      isoforms bind p21 mRNA via direct interaction with a conserved G-quadruplex
      located in its 3' untranslated region. The FXR1P/G-quadruplex complex reduces the
      half-life of p21 mRNA. In the absence of FXR1P, the upregulation of p21 mRNA
      determines the elevated level of its protein product that affects cell-cycle
      progression inducing a premature cell-cycle exit and generating a pool of cells
      blocked at G0. Our study describes a novel role of FXR1P that has crucial
      implications for the understanding of its role during myogenesis and muscle
      development, since we show here that in its absence a reduced number of myoblasts
      will be available for muscle formation/regeneration, shedding new light into the
      pathophysiology of FSHD.

PMID- 23555285
TI  - Long noncoding RNA MALAT1 controls cell cycle progression by regulating the
      expression of oncogenic transcription factor B-MYB.
AB  - The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated
      expression is associated with hyper-proliferation, but the underlying mechanism
      is poorly understood. We demonstrate that MALAT1 levels are regulated during
      normal cell cycle progression. Genome-wide transcriptome analyses in normal human
      diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle
      genes and is required for G1/S and mitotic progression. Depletion of MALAT1 leads
      to activation of p53 and its target genes. The cell cycle defects observed in
      MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major
      downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells
      display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor
      involved in G2/M progression, due to altered binding of splicing factors on B-MYB
      pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes
      cellular proliferation by modulating the expression and/or pre-mRNA processing of
      cell cycle-regulated transcription factors. These findings provide mechanistic
      insights on the role of MALAT1 in regulating cellular proliferation.

PMID- 23555286
TI  - MTL-independent phenotypic switching in Candida tropicalis and a dual role for
      Wor1 in regulating switching and filamentation.
AB  - Phenotypic switching allows for rapid transitions between alternative cell states
      and is important in pathogenic fungi for colonization and infection of different
      host niches. In Candida albicans, the white-opaque phenotypic switch plays a
      central role in regulating the program of sexual mating as well as interactions
      with the mammalian host. White-opaque switching is controlled by genes encoded at
      the MTL (mating-type-like) locus that ensures that only a or alpha cells can
      switch from the white state to the mating-competent opaque state, while a/alpha
      cells are refractory to switching. Here, we show that the related pathogen C.
      tropicalis undergoes white-opaque switching in all three cell types (a, alpha,
      and a/alpha), and thus switching is independent of MTL control. We also
      demonstrate that C. tropicalis white cells are themselves mating-competent,
      albeit at a lower efficiency than opaque cells. Transcriptional profiling of C.
      tropicalis white and opaque cells reveals significant overlap between switch
      regulated genes in MTL homozygous and MTL heterozygous cells, although twice as
      many genes are white-opaque regulated in a/alpha cells as in a cells. In C.
      albicans, the transcription factor Wor1 is the master regulator of the white
      opaque switch, and we show that Wor1 also regulates switching in C. tropicalis;
      deletion of WOR1 locks a, alpha, and a/alpha cells in the white state, while WOR1
      overexpression induces these cells to adopt the opaque state. Furthermore, we
      show that WOR1 overexpression promotes both filamentous growth and biofilm
      formation in C. tropicalis, independent of the white-opaque switch. These results
      demonstrate an expanded role for C. tropicalis Wor1, including the regulation of
      processes necessary for infection of the mammalian host. We discuss these
      findings in light of the ancestral role of Wor1 as a transcriptional regulator of
      the transition between yeast form and filamentous growth.

PMID- 23555287
TI  - Genetic architecture of skin and eye color in an African-European admixed
      population.
AB  - Variation in human skin and eye color is substantial and especially apparent in
      admixed populations, yet the underlying genetic architecture is poorly understood
      because most genome-wide studies are based on individuals of European ancestry.
      We study pigmentary variation in 699 individuals from Cape Verde, where extensive
      West African/European admixture has given rise to a broad range in trait values
      and genomic ancestry proportions. We develop and apply a new approach for
      measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 * 10(-62),
      SLC24A5 P = 9.6 * 10(-9)) that account for both blue versus brown eye color and
      varying intensities of brown eye color. We identify four major loci (SLC24A5 P =
      5.4 * 10(-27), TYR P = 1.1 * 10(-9), APBA2[OCA2] P = 1.5 * 10(-8), SLC45A2 P = 6
      * 10(-9)) for skin color that together account for 35% of the total variance, but
      the genetic component with the largest effect (~44%) is average genomic ancestry.
      Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the
      relationship between skin and eye color, and point to an underlying genetic
      architecture in which several genes of moderate effect act together with many
      genes of small effect to explain ~70% of the estimated heritability.

PMID- 23555288
TI  - Coordination of flower maturation by a regulatory circuit of three microRNAs.
AB  - The development of multicellular organisms relies on interconnected genetic
      programs that control progression through their life cycle. MicroRNAs (miRNAs)
      and transcription factors (TFs) play key roles in such regulatory circuits. Here,
      we describe how three evolutionary conserved miRNA-TF pairs interact to form
      multiple checkpoints during reproductive development of Arabidopsis thaliana.
      Genetic, cellular, and physiological experiments show that miR159- and miR319
      regulated MYB and TCP transcription factors pattern the expression of miR167
      family members and their ARF6/8 targets. Coordinated action of these miRNA-TF
      pairs is crucial for the execution of consecutive hormone-dependent transitions
      during flower maturation. Cross-regulation includes both cis- and trans
      regulatory interactions between these miRNAs and their targets. Our observations
      reveal how different miRNA-TF pairs can be organized into modules that coordinate
      successive steps in the plant life cycle.

PMID- 23555290
TI  - Association mapping and the genomic consequences of selection in sunflower.
AB  - The combination of large-scale population genomic analyses and trait-based
      mapping approaches has the potential to provide novel insights into the
      evolutionary history and genome organization of crop plants. Here, we describe
      the detailed genotypic and phenotypic analysis of a sunflower (Helianthus annuus
      L.) association mapping population that captures nearly 90% of the allelic
      diversity present within the cultivated sunflower germplasm collection. We used
      these data to characterize overall patterns of genomic diversity and to perform
      association analyses on plant architecture (i.e., branching) and flowering time,
      successfully identifying numerous associations underlying these agronomically and
      evolutionarily important traits. Overall, we found variable levels of linkage
      disequilibrium (LD) across the genome. In general, islands of elevated LD
      correspond to genomic regions underlying traits that are known to have been
      targeted by selection during the evolution of cultivated sunflower. In many
      cases, these regions also showed significantly elevated levels of differentiation
      between the two major sunflower breeding groups, consistent with the occurrence
      of divergence due to strong selection. One of these regions, which harbors a
      major branching locus, spans a surprisingly long genetic interval (ca. 25 cM),
      indicating the occurrence of an extended selective sweep in an otherwise
      recombinogenic interval.

PMID- 23555289
TI  - CRL2(LRR-1) E3-ligase regulates proliferation and progression through meiosis in
      the Caenorhabditis elegans germline.
AB  - The ubiquitin-proteolytic system controls the stability of proteins in space and
      time. In this study, using a temperature-sensitive mutant allele of the cul-2
      gene, we show that CRL2(LRR-1) (CUL-2 RING E3 ubiquitin-ligase and the Leucine
      Rich Repeat 1 substrate recognition subunit) acts at multiple levels to control
      germline development. CRL2(LRR-1) promotes germ cell proliferation by
      counteracting the DNA replication ATL-1 checkpoint pathway. CRL2(LRR-1) also
      participates in the mitotic proliferation/meiotic entry decision, presumably
      controlling the stability of meiotic promoting factors in the mitotic zone of the
      germline. Finally, CRL2(LRR-1) inhibits the first steps of meiotic prophase by
      targeting in mitotic germ cells degradation of the HORMA domain-containing
      protein HTP-3, required for loading synaptonemal complex components onto meiotic
      chromosomes. Given its widespread evolutionary conservation, CUL-2 may similarly
      regulate germline development in other organisms as well.

PMID- 23555292
TI  - Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney
      development.
AB  - Yap is a transcriptional co-activator that regulates cell proliferation and
      apoptosis downstream of the Hippo kinase pathway. We investigated Yap function
      during mouse kidney development using a conditional knockout strategy that
      specifically inactivated Yap within the nephrogenic lineage. We found that Yap is
      essential for nephron induction and morphogenesis, surprisingly, in a manner
      independent of regulation of cell proliferation and apoptosis. We used microarray
      analysis to identify a suite of novel Yap-dependent genes that function during
      nephron formation and have been implicated in morphogenesis. Previous in vitro
      studies have indicated that Yap can respond to mechanical stresses in cultured
      cells downstream of the small GTPases RhoA. We find that tissue-specific
      inactivation of the Rho GTPase Cdc42 causes a severe defect in nephrogenesis that
      strikingly phenocopies loss of Yap. Ablation of Cdc42 decreases nuclear
      localization of Yap, leading to a reduction of Yap-dependent gene expression. We
      propose that Yap responds to Cdc42-dependent signals in nephron progenitor cells
      to activate a genetic program required to shape the functioning nephron.

PMID- 23555293
TI  - Genome-wide control of RNA polymerase II activity by cohesin.
AB  - Cohesin is a well-known mediator of sister chromatid cohesion, but it also
      influences gene expression and development. These non-canonical roles of cohesin
      are not well understood, but are vital: gene expression and development are
      altered by modest changes in cohesin function that do not disrupt chromatid
      cohesion. To clarify cohesin's roles in transcription, we measured how cohesin
      controls RNA polymerase II (Pol II) activity by genome-wide chromatin
      immunoprecipitation and precision global run-on sequencing. On average, cohesin
      binding genes have more transcriptionally active Pol II and promoter-proximal Pol
      II pausing than non-binding genes, and are more efficient, producing higher
      steady state levels of mRNA per transcribing Pol II complex. Cohesin depletion
      frequently decreases gene body transcription but increases pausing at cohesin
      binding genes, indicating that cohesin often facilitates transition of paused Pol
      II to elongation. In many cases, this likely reflects a role for cohesin in
      transcriptional enhancer function. Strikingly, more than 95% of predicted
      extragenic enhancers bind cohesin, and cohesin depletion can reduce their
      association with Pol II, indicating that cohesin facilitates enhancer-promoter
      contact. Cohesin depletion decreases the levels of transcriptionally engaged Pol
      II at the promoters of most genes that don't bind cohesin, suggesting that
      cohesin controls expression of one or more broadly acting general transcription
      factors. The multiple transcriptional roles of cohesin revealed by these studies
      likely underlie the growth and developmental deficits caused by minor changes in
      cohesin activity.

PMID- 23555291
TI  - Trans-ethnic fine-mapping of lipid loci identifies population-specific signals
      and allelic heterogeneity that increases the trait variance explained.
AB  - Genome-wide association studies (GWAS) have identified ~100 loci associated with
      blood lipid levels, but much of the trait heritability remains unexplained, and
      at most loci the identities of the trait-influencing variants remain unknown. We
      conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the
      Metabochip for their association with triglycerides (TG), high-density
      lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C),
      respectively, in individuals of African American (n = 6,832), East Asian (n =
      9,449), and European (n = 10,829) ancestry. We aimed to identify the variants
      with strongest association at each locus, identify additional and population
      specific signals, refine association signals, and assess the relative
      significance of previously described functional variants. Among the 58 loci, 33
      exhibited evidence of association at P<1 * 10(-4) in at least one ancestry group.
      Sequential conditional analyses revealed that ten, nine, and four loci in African
      Americans, Europeans, and East Asians, respectively, exhibited two or more
      signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold
      increase in the explained phenotypic variance compared to the strongest signals.
      Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans
      ethnic analyses narrowed the signals to smaller sets of variants at GCKR,
      PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have
      functional effects, 74% exhibited the strongest association at the respective
      signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm
      the presence of allelic heterogeneity, allow the identification of population
      specific variants, and limit the number of candidate SNPs for functional studies.

PMID- 23555294
TI  - Mouse HFM1/Mer3 is required for crossover formation and complete synapsis of
      homologous chromosomes during meiosis.
AB  - Faithful chromosome segregation during meiosis requires that homologous
      chromosomes associate and recombine. Chiasmata, the cytological manifestation of
      recombination, provide the physical link that holds the homologs together as a
      pair, facilitating their orientation on the spindle at meiosis I. Formation of
      most crossover (CO) events requires the assistance of a group of proteins
      collectively known as ZMM. HFM1/Mer3 is in this group of proteins and is required
      for normal progression of homologous recombination and proper synapsis between
      homologous chromosomes in a number of model organisms. Our work is the first
      study in mammals showing the in vivo function of mouse HFM1. Cytological
      observations suggest that initial steps of recombination are largely normal in a
      majority of Hfm1(-/-) spermatocytes. Intermediate and late stages of
      recombination appear aberrant, as chromosomal localization of MSH4 is altered and
      formation of MLH1foci is drastically reduced. In agreement, chiasma formation is
      reduced, and cells arrest with subsequent apoptosis at diakinesis. Our results
      indicate that deletion of Hfm1 leads to the elimination of a major fraction but
      not all COs. Formation of chromosome axial elements and homologous pairing is
      apparently normal, and Hfm1(-/-) spermatocytes progress to the end of prophase I
      without apparent developmental delay or apoptosis. However, synapsis is altered
      with components of the central region of the synaptonemal complex frequently
      failing to extend the full length of the chromosome axes. We propose that initial
      steps of recombination are sufficient to support homology recognition, pairing,
      and initial chromosome synapsis and that HFM1 is required to form normal numbers
      of COs and to complete synapsis.

PMID- 23555295
TI  - Divergent selection drives genetic differentiation in an R2R3-MYB transcription
      factor that contributes to incipient speciation in Mimulus aurantiacus.
AB  - Identifying the molecular genetic basis of traits contributing to speciation is
      of crucial importance for understanding the ecological and evolutionary
      mechanisms that generate biodiversity. Despite several examples describing
      putative "speciation genes," it is often uncertain to what extent these genetic
      changes have contributed to gene flow reductions in nature. Therefore,
      considerable interest lies in characterizing the molecular basis of traits that
      actively confer reproductive isolation during the early stages of speciation, as
      these loci can be attributed directly to the process of divergence. In Southern
      California, two ecotypes of Mimulus aurantiacus are parapatric and differ
      primarily in flower color, with an anthocyanic, red-flowered morph in the west
      and an anthocyanin-lacking, yellow-flowered morph in the east. Evidence suggests
      that the genetic changes responsible for this shift in flower color have been
      essential for divergence and have become fixed in natural populations of each
      ecotype due to almost complete differences in pollinator preference. In this
      study, we demonstrate that a cis-regulatory mutation in an R2R3-MYB transcription
      factor results in differential regulation of enzymes in the anthocyanin
      biosynthetic pathway and is the major contributor to differences in floral
      pigmentation. In addition, molecular population genetic data show that, despite
      gene flow at neutral loci, divergent selection has driven the fixation of
      alternate alleles at this gene between ecotypes. Therefore, by identifying the
      genetic basis underlying ecologically based divergent selection in flower color
      between these ecotypes, we have revealed the ecological and functional mechanisms
      involved in the evolution of pre-mating isolation at the early stages of
      incipient speciation.

PMID- 23555296
TI  - The role of ATM in the deficiency in nonhomologous end-joining near telomeres in
      a human cancer cell line.
AB  - Telomeres distinguish chromosome ends from double-strand breaks (DSBs) and
      prevent chromosome fusion. However, telomeres can also interfere with DNA repair,
      as shown by a deficiency in nonhomologous end joining (NHEJ) and an increase in
      large deletions at telomeric DSBs. The sensitivity of telomeric regions to DSBs
      is important in the cellular response to ionizing radiation and oncogene-induced
      replication stress, either by preventing cell division in normal cells, or by
      promoting chromosome instability in cancer cells. We have previously proposed
      that the telomeric protein TRF2 causes the sensitivity of telomeric regions to
      DSBs, either through its inhibition of ATM, or by promoting the processing of
      DSBs as though they are telomeres, which is independent of ATM. Our current study
      addresses the mechanism responsible for the deficiency in repair of DSBs near
      telomeres by combining assays for large deletions, NHEJ, small deletions, and
      gross chromosome rearrangements (GCRs) to compare the types of events resulting
      from DSBs at interstitial and telomeric DSBs. Our results confirm the sensitivity
      of telomeric regions to DSBs by demonstrating that the frequency of GCRs is
      greatly increased at DSBs near telomeres and that the role of ATM in DSB repair
      is very different at interstitial and telomeric DSBs. Unlike at interstitial
      DSBs, a deficiency in ATM decreases NHEJ and small deletions at telomeric DSBs,
      while it increases large deletions. These results strongly suggest that ATM is
      functional near telomeres and is involved in end protection at telomeric DSBs,
      but is not required for the extensive resection at telomeric DSBs. The results
      support our model in which the deficiency in DSB repair near telomeres is a
      result of ATM-independent processing of DSBs as though they are telomeres,
      leading to extensive resection, telomere loss, and GCRs involving alternative
      NHEJ.

PMID- 23555297
TI  - Ancient evolutionary trade-offs between yeast ploidy states.
AB  - The number of chromosome sets contained within the nucleus of eukaryotic
      organisms is a fundamental yet evolutionarily poorly characterized genetic
      variable of life. Here, we mapped the impact of ploidy on the mitotic fitness of
      baker's yeast and its never domesticated relative Saccharomyces paradoxus across
      wide swaths of their natural genotypic and phenotypic space. Surprisingly,
      environment-specific influences of ploidy on reproduction were found to be the
      rule rather than the exception. These ploidy-environment interactions were well
      conserved across the 2 billion generations separating the two species, suggesting
      that they are the products of strong selection. Previous hypotheses of
      generalizable advantages of haploidy or diploidy in ecological contexts imposing
      nutrient restriction, toxin exposure, and elevated mutational loads were rejected
      in favor of more fine-grained models of the interplay between ecology and ploidy.
      On a molecular level, cell size and mating type locus composition had equal, but
      limited, explanatory power, each explaining 12.5%-17% of ploidy-environment
      interactions. The mechanism of the cell size-based superior reproductive
      efficiency of haploids during Li(+) exposure was traced to the Li(+) exporter
      ENA. Removal of the Ena transporters, forcing dependence on the Nha1 extrusion
      system, completely altered the effects of ploidy on Li(+) tolerance and evoked a
      strong diploid superiority, demonstrating how genetic variation at a single locus
      can completely reverse the relative merits of haploidy and diploidy. Taken
      together, our findings unmasked a dynamic interplay between ploidy and ecology
      that was of unpredicted evolutionary importance and had multiple molecular roots.

PMID- 23555298
TI  - Molecular networks of human muscle adaptation to exercise and age.
AB  - Physical activity and molecular ageing presumably interact to precipitate
      musculoskeletal decline in humans with age. Herein, we have delineated molecular
      networks for these two major components of sarcopenic risk using multiple
      independent clinical cohorts. We generated genome-wide transcript profiles from
      individuals (n = 44) who then undertook 20 weeks of supervised resistance
      exercise training (RET). Expectedly, our subjects exhibited a marked range of
      hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis
      (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we
      identified rapamycin (mTOR) signaling associating with growth (P = 1.4 * 10(
      30)). Paradoxically, those displaying most hypertrophy exhibited an inhibited
      mTOR activation signature, including the striking down-regulation of 70 rRNAs.
      Differential analysis found networks mimicking developmental processes (activated
      all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 * 10(-13)) and inhibited aryl
      hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 * 10(-7))) with RET.
      Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise
      training (EET), they appear to represent "generic" physical activity responsive
      gene-networks. For age, we found that differential gene-expression methods do not
      produce consistent molecular differences between young versus old individuals.
      Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum
      of subject ages (18-78 y), the first reproducible set of age-related transcripts
      in human muscle was identified. This analysis identified ~500 genes highly
      enriched in post-transcriptional processes (P = 1 * 10(-6)) and with negligible
      links to the aforementioned generic exercise regulated gene-sets and some overlap
      with ribosomal genes. The RNA signatures from multiple compounds all targeting
      serotonin, DNA topoisomerase antagonism, and RXR activation were significantly
      related to the muscle age-related genes. Finally, a number of specific
      chromosomal loci, including 1q12 and 13q21, contributed by more than chance to
      the age-related gene list (P = 0.01-0.005), implying possible epigenetic events.
      We conclude that human muscle age-related molecular processes appear distinct
      from the processes regulated by those of physical activity.

PMID- 23555299
TI  - A gene transfer agent and a dynamic repertoire of secretion systems hold the keys
      to the explosive radiation of the emerging pathogen Bartonella.
AB  - Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial
      genome. A novel putative GTA was recently discovered in the mouse-infecting
      bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically
      diverse bacteria, their role in evolution is largely unknown. Here, we present a
      comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size,
      including six novel genomes from Bartonella isolated from a cow, two moose, two
      dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core
      genes indicates that the deadly human pathogen B. bacilliformis is related to the
      ruminant-adapted clade, rather than being the earliest diverging species in the
      genus as previously thought. A gene flux analysis identified 12 genes for a GTA
      and a phage-derived origin of replication as the most conserved innovations.
      These are located in a region of a few hundred kb that also contains 8 insertions
      of gene clusters for type III, IV, and V secretion systems, and genes for
      putatively secreted molecules such as cholera-like toxins. The phylogenies
      indicate a recent transfer of seven genes in the virB gene cluster for a type IV
      secretion system from a cat-adapted B. henselae to a dog-adapted B. vinsonii
      strain. We show that the B. henselae GTA is functional and can transfer genes in
      vitro. We suggest that the maintenance of the GTA is driven by selection to
      increase the likelihood of horizontal gene transfer and argue that this process
      is beneficial at the population level, by facilitating adaptive evolution of the
      host-adaptation systems and thereby expansion of the host range size. The process
      counters gene loss and forces all cells to contribute to the production of the
      GTA and the secreted molecules. The results advance our understanding of the role
      that GTAs play for the evolution of bacterial genomes.

PMID- 23555300
TI  - Genome-wide association study and gene expression analysis identifies CD84 as a
      predictor of response to etanercept therapy in rheumatoid arthritis.
AB  - Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used
      treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail
      to respond adequately to anti-TNF therapy, which limits the development of
      clinical biomarkers to predict response or new drugs to target refractory cases.
      To understand the biological basis of response to anti-TNF therapy, we conducted
      a genome-wide association study (GWAS) meta-analysis of more than 2 million
      common variants in 2,706 RA patients from 13 different collections. Patients were
      treated with one of three anti-TNF medications: etanercept (n = 733), infliximab
      (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23
      locus that was associated with change in disease activity score (DeltaDAS) in the
      etanercept subset of patients (P = 8 * 10(-8)), but not in the infliximab or
      adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor
      binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele
      associated with better response to etanercept was associated with higher CD84
      gene expression in peripheral blood mononuclear cells (P = 1 * 10(-11) in 228 non
      RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic
      findings, higher CD84 gene expression correlated with lower cross-sectional DAS
      (P = 0.02, n = 210) and showed a non-significant trend for better DeltaDAS in a
      subset of RA patients with gene expression data (n = 31, etanercept-treated). A
      small, multi-ethnic replication showed a non-significant trend towards an
      association among etanercept-treated RA patients of Portuguese ancestry (n = 139,
      P = 0.4), but no association among patients of Japanese ancestry (n = 151, P =
      0.8). Our study demonstrates that an allele associated with response to
      etanercept therapy is also associated with CD84 gene expression, and further that
      CD84 expression correlates with disease activity. These findings support a model
      in which CD84 genotypes and/or expression may serve as a useful biomarker for
      response to etanercept treatment in RA patients of European ancestry.

PMID- 23555302
TI  - Robust prediction of expression differences among human individuals using only
      genotype information.
AB  - Many genetic variants that are significantly correlated to gene expression
      changes across human individuals have been identified, but the ability of these
      variants to predict expression of unseen individuals has rarely been evaluated.
      Here, we devise an algorithm that, given training expression and genotype data
      for a set of individuals, predicts the expression of genes of unseen test
      individuals given only their genotype in the local genomic vicinity of the
      predicted gene. Notably, the resulting predictions are remarkably robust in that
      they agree well between the training and test sets, even when the training and
      test sets consist of individuals from distinct populations. Thus, although the
      overall number of genes that can be predicted is relatively small, as expected
      from our choice to ignore effects such as environmental factors and trans
      sequence variation, the robust nature of the predictions means that the identity
      and quantitative degree to which genes can be predicted is known in advance. We
      also present an extension that incorporates heterogeneous types of genomic
      annotations to differentially weigh the importance of the various genetic
      variants, and we show that assigning higher weights to variants with particular
      annotations such as proximity to genes and high regional G/C content can further
      improve the predictions. Finally, genes that are successfully predicted have, on
      average, higher expression and more variability across individuals, providing
      insight into the characteristics of the types of genes that can be predicted from
      their cis genetic variation.

PMID- 23555301
TI  - A novel function for the Hox gene Abd-B in the male accessory gland regulates the
      long-term female post-mating response in Drosophila.
AB  - In insects, products of the male reproductive tract are essential for initiating
      and maintaining the female post-mating response (PMR). The PMR includes changes
      in egg laying, receptivity to courting males, and sperm storage. In Drosophila,
      previous studies have determined that the main cells of the male accessory gland
      produce some of the products required for these processes. However, nothing was
      known about the contribution of the gland's other secretory cell type, the
      secondary cells. In the course of investigating the late functions of the
      homeotic gene, Abdominal-B (Abd-B), we discovered that Abd-B is specifically
      expressed in the secondary cells of the Drosophila male accessory gland. Using an
      Abd-B BAC reporter coupled with a collection of genetic deletions, we discovered
      an enhancer from the iab-6 regulatory domain that is responsible for Abd-B
      expression in these cells and that apparently works independently from the
      segmentally regulated chromatin domains of the bithorax complex. Removal of this
      enhancer results in visible morphological defects in the secondary cells. We
      determined that mates of iab-6 mutant males show defects in long-term egg laying
      and suppression of receptivity, and that products of the secondary cells are
      influential during sperm competition. Many of these phenotypes seem to be caused
      by a defect in the storage and gradual release of sex peptide in female mates of
      iab-6 mutant males. We also found that Abd-B expression in the secondary cells
      contributes to glycosylation of at least three accessory gland proteins: ovulin
      (Acp26Aa), CG1656, and CG1652. Our results demonstrate that long-term post-mating
      changes observed in mated females are not solely induced by main cell secretions,
      as previously believed, but that secondary cells also play an important role in
      male fertility by extending the female PMR. Overall, these discoveries provide
      new insights into how these two cell types cooperate to produce and maintain a
      robust female PMR.

PMID- 23555303
TI  - Nuclear myosin 1c facilitates the chromatin modifications required to activate
      rRNA gene transcription and cell cycle progression.
AB  - Actin and nuclear myosin 1c (NM1) cooperate in RNA polymerase I (pol I)
      transcription. NM1 is also part of a multiprotein assembly, B-WICH, which is
      involved in transcription. This assembly contains the chromatin remodeling
      complex WICH with its subunits WSTF and SNF2h. We report here that NM1 binds
      SNF2h with enhanced affinity upon impairment of the actin-binding function. ChIP
      analysis revealed that NM1, SNF2h, and actin gene occupancies are cell cycle
      dependent and require intact motor function. At the onset of cell division, when
      transcription is temporarily blocked, B-WICH is disassembled due to WSTF
      phosphorylation, to be reassembled on the active gene at exit from mitosis. NM1
      gene knockdown and motor function inhibition, or stable expression of NM1 mutants
      that do not interact with actin or chromatin, overall repressed rRNA synthesis by
      stalling pol I at the gene promoter, led to chromatin alterations by changing the
      state of H3K9 acetylation at gene promoter, and delayed cell cycle progression.
      These results suggest a unique structural role for NM1 in which the interaction
      with SNF2h stabilizes B-WICH at the gene promoter and facilitates recruitment of
      the HAT PCAF. This leads to a permissive chromatin structure required for
      transcription activation.

PMID- 23555304
TI  - Dynamic circadian protein-protein interaction networks predict temporal
      organization of cellular functions.
AB  - Essentially all biological processes depend on protein-protein interactions
      (PPIs). Timing of such interactions is crucial for regulatory function. Although
      circadian (~24-hour) clocks constitute fundamental cellular timing mechanisms
      regulating important physiological processes, PPI dynamics on this timescale are
      largely unknown. Here, we identified 109 novel PPIs among circadian clock
      proteins via a yeast-two-hybrid approach. Among them, the interaction of protein
      phosphatase 1 and CLOCK/BMAL1 was found to result in BMAL1 destabilization. We
      constructed a dynamic circadian PPI network predicting the PPI timing using
      circadian expression data. Systematic circadian phenotyping (RNAi and
      overexpression) suggests a crucial role for components involved in dynamic
      interactions. Systems analysis of a global dynamic network in liver revealed that
      interacting proteins are expressed at similar times likely to restrict regulatory
      interactions to specific phases. Moreover, we predict that circadian PPIs
      dynamically connect many important cellular processes (signal transduction, cell
      cycle, etc.) contributing to temporal organization of cellular physiology in an
      unprecedented manner.

PMID- 23555305
TI  - The Tomato Yellow Leaf Curl Virus resistance genes Ty-1 and Ty-3 are allelic and
      code for DFDGD-class RNA-dependent RNA polymerases.
AB  - Tomato Yellow Leaf Curl Virus Disease incited by Tomato yellow leaf curl virus
      (TYLCV) causes huge losses in tomato production worldwide and is caused by
      different related begomovirus species. Breeding for TYLCV resistance has been
      based on the introgression of multiple resistance genes originating from several
      wild tomato species. In this study we have fine-mapped the widely used Solanum
      chilense-derived Ty-1 and Ty-3 genes by screening nearly 12,000 plants for
      recombination events and generating recombinant inbred lines. Multiple molecular
      markers were developed and used in combination with disease tests to fine-map the
      genes to a small genomic region (approximately 70 kb). Using a Tobacco Rattle
      Virus-Virus Induced Gene Silencing approach, the resistance gene was identified.
      It is shown that Ty-1 and Ty-3 are allelic and that they code for a RNA-dependent
      RNA polymerase (RDR) belonging to the RDRgamma type, which has an atypical DFDGD
      motif in the catalytic domain. In contrast to the RDRalpha type, characterized by
      a catalytic DLDGD motif, no clear function has yet been described for the
      RDRgamma type, and thus the Ty-1/Ty-3 gene unveils a completely new class of
      resistance gene. Although speculative, the resistance mechanism of Ty-1/Ty-3 and
      its specificity towards TYLCV are discussed in light of the function of the
      related RDRalpha class in the amplification of the RNAi response in plants and
      transcriptional silencing of geminiviruses in plants.

PMID- 23555306
TI  - Differential evolutionary fate of an ancestral primate endogenous retrovirus
      envelope gene, the EnvV syncytin, captured for a function in placentation.
AB  - Syncytins are envelope genes of retroviral origin that have been co-opted for a
      role in placentation. They promote cell-cell fusion and are involved in the
      formation of a syncytium layer--the syncytiotrophoblast--at the materno-fetal
      interface. They were captured independently in eutherian mammals, and knockout
      mice demonstrated that they are absolutely required for placenta formation and
      embryo survival. Here we provide evidence that these "necessary" genes acquired
      "by chance" have a definite lifetime with diverse fates depending on the animal
      lineage, being both gained and lost in the course of evolution. Analysis of a
      retroviral envelope gene, the envV gene, present in primate genomes and belonging
      to the endogenous retrovirus type V (ERV-V) provirus, shows that this captured
      gene, which entered the primate lineage >45 million years ago, behaves as a
      syncytin in Old World monkeys, but lost its canonical fusogenic activity in other
      primate lineages, including humans. In the Old World monkeys, we show--by in situ
      analyses and ex vivo assays--that envV is both specifically expressed at the
      level of the placental syncytiotrophoblast and fusogenic, and that it further
      displays signs of purifying selection based on analysis of non-synonymous to
      synonymous substitution rates. We further show that purifying selection still
      operates in the primate lineages where the gene is no longer fusogenic,
      indicating that degeneracy of this ancestral syncytin is a slow, lineage
      dependent, and multi-step process, in which the fusogenic activity would be the
      first canonical property of this retroviral envelope gene to be lost.

PMID- 23555307
TI  - Long interspersed element-1 (LINE-1): passenger or driver in human neoplasms?
AB  - LINE-1 (L1) retrotransposons make up a significant portion of human genomes, with
      an estimated 500,000 copies per genome. Like other retrotransposons, L1
      retrotransposons propagate through RNA sequences that are reverse transcribed
      into DNA sequences, which are integrated into new genomic loci. L1 somatic
      insertions have the potential to disrupt the transcriptome by inserting into or
      nearby genes. By mutating genes and playing a role in epigenetic dysregulation,
      L1 transposons may contribute to tumorigenesis. Studies of the "mobilome" have
      lagged behind other tumor characterizations at the sequence, transcript, and
      epigenetic levels. Here, we consider evidence that L1 retrotransposons may
      sometimes drive human tumorigenesis.

PMID- 23555308
TI  - A feed-forward loop coupling extracellular BMP transport and morphogenesis in
      Drosophila wing.
AB  - A variety of extracellular factors regulate morphogenesis during development.
      However, coordination between extracellular signaling and dynamic morphogenesis
      is largely unexplored. We address the fundamental question by studying posterior
      crossvein (PCV) development in Drosophila as a model, in which long-range BMP
      transport from the longitudinal veins plays a critical role during the pupal
      stages. Here, we show that RhoGAP Crossveinless-C (Cv-C) is induced at the PCV
      primordial cells by BMP signaling and mediates PCV morphogenesis cell
      autonomously by inactivating members of the Rho-type small GTPases. Intriguingly,
      we find that Cv-C is also required non-cell-autonomously for BMP transport into
      the PCV region, while a long-range BMP transport is guided toward ectopic wing
      vein regions by loss of the Rho-type small GTPases. We present evidence that low
      level of beta-integrin accumulation at the basal side of PCV epithelial cells
      regulated by Cv-C provides an optimal extracellular environment for guiding BMP
      transport. These data suggest that BMP transport and PCV morphogenesis are
      tightly coupled. Our study reveals a feed-forward mechanism that coordinates the
      spatial distribution of extracellular instructive cues and morphogenesis. The
      coupling mechanism may be widely utilized to achieve precise morphogenesis during
      development and homeostasis.

PMID- 23555310
TI  - Elevated expression of the integrin-associated protein PINCH suppresses the
      defects of Drosophila melanogaster muscle hypercontraction mutants.
AB  - A variety of human diseases arise from mutations that alter muscle contraction.
      Evolutionary conservation allows genetic studies in Drosophila melanogaster to be
      used to better understand these myopathies and suggest novel therapeutic
      strategies. Integrin-mediated adhesion is required to support muscle structure
      and function, and expression of Integrin adhesive complex (IAC) proteins is
      modulated to adapt to varying levels of mechanical stress within muscle.
      Mutations in flapwing (flw), a catalytic subunit of myosin phosphatase, result in
      non-muscle myosin hyperphosphorylation, as well as muscle hypercontraction,
      defects in size, motility, muscle attachment, and subsequent larval and pupal
      lethality. We find that moderately elevated expression of the IAC protein PINCH
      significantly rescues flw phenotypes. Rescue requires PINCH be bound to its
      partners, Integrin-linked kinase and Ras suppressor 1. Rescue is not achieved
      through dephosphorylation of non-muscle myosin, suggesting a mechanism in which
      elevated PINCH expression strengthens integrin adhesion. In support of this,
      elevated expression of PINCH rescues an independent muscle hypercontraction
      mutant in muscle myosin heavy chain, Mhc(Samba1). By testing a panel of IAC
      proteins, we show specificity for PINCH expression in the rescue of
      hypercontraction mutants. These data are consistent with a model in which PINCH
      is present in limiting quantities within IACs, with increasing PINCH expression
      reinforcing existing adhesions or allowing for the de novo assembly of new
      adhesion complexes. Moreover, in myopathies that exhibit hypercontraction,
      strategic PINCH expression may have therapeutic potential in preserving muscle
      structure and function.

PMID- 23555309
TI  - Twist1 controls a cell-specification switch governing cell fate decisions within
      the cardiac neural crest.
AB  - Neural crest cells are multipotent progenitor cells that can generate both
      ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth
      muscle. The mechanisms controlling this cell fate choice are not known. The basic
      Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the
      migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of
      the Twist-box causes differentiation of ectopic neuronal cells, which molecularly
      resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with
      the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b
      promoter to repress transcriptional activity. Mesodermal cardiac neural crest
      trans-differentiation into ectodermal sympathetic ganglia-like neurons is
      dependent upon Phox2b function. Ectopic Twist1 expression in neural crest
      precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1
      functions in post-migratory neural crest cells to repress pro-neural factors and
      thereby regulate cell fate determination between ectodermal and mesodermal
      lineages.

PMID- 23555311
TI  - A copy number variant at the KITLG locus likely confers risk for canine squamous
      cell carcinoma of the digit.
AB  - The domestic dog is a robust model for studying the genetics of complex disease
      susceptibility. The strategies used to develop and propagate modern breeds have
      resulted in an elevated risk for specific diseases in particular breeds. One
      example is that of Standard Poodles (STPOs), who have increased risk for squamous
      cell carcinoma of the digit (SCCD), a locally aggressive cancer that causes lytic
      bone lesions, sometimes with multiple toe recurrence. However, only STPOs of dark
      coat color are at high risk; light colored STPOs are almost entirely unaffected,
      suggesting that interactions between multiple pathways are necessary for
      oncogenesis. We performed a genome-wide association study (GWAS) on STPOs,
      comparing 31 SCCD cases to 34 unrelated black STPO controls. The peak SNP on
      canine chromosome 15 was statistically significant at the genome-wide level
      (P(raw) = 1.60 * 10(-7); P(genome) = 0.0066). Additional mapping resolved the
      region to the KIT Ligand (KITLG) locus. Comparison of STPO cases to other at-risk
      breeds narrowed the locus to a 144.9-Kb region. Haplotype mapping among 84 STPO
      cases identified a minimal region of 28.3 Kb. A copy number variant (CNV)
      containing predicted enhancer elements was found to be strongly associated with
      SCCD in STPOs (P = 1.72 * 10(-8)). Light colored STPOs carry the CNV risk alleles
      at the same frequency as black STPOs, but are not susceptible to SCCD. A GWAS
      comparing 24 black and 24 light colored STPOs highlighted only the MC1R locus as
      significantly different between the two datasets, suggesting that a compensatory
      mutation within the MC1R locus likely protects light colored STPOs from disease.
      Our findings highlight a role for KITLG in SCCD susceptibility, as well as
      demonstrate that interactions between the KITLG and MC1R loci are potentially
      required for SCCD oncogenesis. These findings highlight how studies of breed
      limited diseases are useful for disentangling multigene disorders.

PMID- 23555312
TI  - The role of the Arabidopsis Exosome in siRNA-independent silencing of
      heterochromatic loci.
AB  - The exosome functions throughout eukaryotic RNA metabolism and has a prominent
      role in gene silencing in yeast. In Arabidopsis, exosome regulates expression of
      a "hidden" transcriptome layer from centromeric, pericentromeric, and other
      heterochromatic loci that are also controlled by small (sm)RNA-based de novo DNA
      methylation (RdDM). However, the relationship between exosome and smRNAs in gene
      silencing in Arabidopsis remains unexplored. To investigate whether exosome
      interacts with RdDM, we profiled Arabidopsis smRNAs by deep sequencing in exosome
      and RdDM mutants and also analyzed RdDM-controlled loci. We found that exosome
      loss had a very minor effect on global smRNA populations, suggesting that, in
      contrast to fission yeast, in Arabidopsis the exosome does not control the
      spurious entry of RNAs into smRNA pathways. Exosome defects resulted in decreased
      histone H3K9 dimethylation at RdDM-controlled loci, without affecting smRNAs or
      DNA methylation. Exosome also exhibits a strong genetic interaction with RNA Pol
      V, but not Pol IV, and physically associates with transcripts produced from the
      scaffold RNAs generating region. We also show that two Arabidopsis rrp6
      homologues act in gene silencing. Our data suggest that Arabidopsis exosome may
      act in parallel with RdDM in gene silencing, by epigenetic effects on chromatin
      structure, not through siRNAs or DNA methylation.

PMID- 23555313
TI  - Statistical analysis reveals co-expression patterns of many pairs of genes in
      yeast are jointly regulated by interacting loci.
AB  - Expression quantitative trait loci (eQTL) studies have generated large amounts of
      data in different organisms. The analyses of these data have led to many novel
      findings and biological insights on expression regulations. However, the role of
      epistasis in the joint regulation of multiple genes has not been explored. This
      is largely due to the computational complexity involved when multiple traits are
      simultaneously considered against multiple markers if an exhaustive search
      strategy is adopted. In this article, we propose a computationally feasible
      approach to identify pairs of chromosomal regions that interact to regulate co
      expression patterns of pairs of genes. Our approach is built on a bivariate model
      whose covariance matrix depends on the joint genotypes at the candidate loci. We
      also propose a filtering process to reduce the computational burden. When we
      applied our method to a yeast eQTL dataset profiled under both the glucose and
      ethanol conditions, we identified a total of 225 and 224 modules, with each
      module consisting of two genes and two eQTLs where the two eQTLs epistatically
      regulate the co-expression patterns of the two genes. We found that many of these
      modules have biological interpretations. Under the glucose condition, ribosome
      biogenesis was co-regulated with the signaling and carbohydrate catabolic
      processes, whereas silencing and aging related genes were co-regulated under the
      ethanol condition with the eQTLs containing genes involved in oxidative stress
      response process.

PMID- 23555314
TI  - A single cohesin complex performs mitotic and meiotic functions in the protist
      tetrahymena.
AB  - The cohesion of sister chromatids in the interval between chromosome replication
      and anaphase is important for preventing the precocious separation, and hence
      nondisjunction, of chromatids. Cohesion is accomplished by a ring-shaped protein
      complex, cohesin; and its release at anaphase occurs when separase cleaves the
      complex's alpha-kleisin subunit. Cohesin has additional roles in facilitating DNA
      damage repair from the sister chromatid and in regulating gene expression. We
      tested the universality of the present model of cohesion by studying cohesin in
      the evolutionarily distant protist Tetrahymena thermophila. Localization of
      tagged cohesin components Smc1p and Rec8p (the alpha-kleisin) showed that cohesin
      is abundant in mitotic and meiotic nuclei. RNAi knockdown experiments
      demonstrated that cohesin is crucial for normal chromosome segregation and
      meiotic DSB repair. Unexpectedly, cohesin does not detach from chromosome arms in
      anaphase, yet chromosome segregation depends on the activity of separase (Esp1p).
      When Esp1p is depleted by RNAi, chromosomes become polytenic as they undergo
      multiple rounds of replication, but fail to separate. The cohesion of such
      bundles of numerous chromatids suggests that chromatids may be connected by
      factors in addition to topological linkage by cohesin rings. Although cohesin is
      not detected in transcriptionally active somatic nuclei, its loss causes a slight
      defect in their amitotic division. Notably, Tetrahymena uses a single version of
      alpha-kleisin for both mitosis and meiosis. Therefore, we propose that the
      differentiation of mitotic and meiotic cohesins found in most other model systems
      is not due to the need of a specialized meiotic cohesin, but due to additional
      roles of mitotic cohesin.

PMID- 23555315
TI  - Genome-wide testing of putative functional exonic variants in relationship with
      breast and prostate cancer risk in a multiethnic population.
AB  - Rare variation in protein coding sequence is poorly captured by GWAS arrays and
      has been hypothesized to contribute to disease heritability. Using the Illumina
      HumanExome SNP array, we successfully genotyped 191,032 common and rare non
      synonymous, splice site, or nonsense variants in a multiethnic sample of 2,984
      breast cancer cases, 4,376 prostate cancer cases, and 7,545 controls. In breast
      cancer, the strongest associations included either SNPs in or gene burden scores
      for genes LDLRAD1, SLC19A1, FGFBP3, CASP5, MMAB, SLC16A6, and INS-IGF2. In
      prostate cancer, one of the most associated SNPs was in the gene GPRC6A
      (rs2274911, Pro91Ser, OR = 0.88, P = 1.3 * 10(-5)) near to a known risk locus for
      prostate cancer; other suggestive associations were noted in genes such as F13A1,
      ANXA4, MANSC1, and GP6. For both breast and prostate cancer, several of the most
      significant associations involving SNPs or gene burden scores (sum of minor
      alleles) were noted in genes previously reported to be associated with a cancer
      related phenotype. However, only one of the associations (rs145889899 in LDLRAD1,
      p = 2.5 * 10(-7) only seen in African Americans) for overall breast or prostate
      cancer risk was statistically significant after correcting for multiple
      comparisons. In addition to breast and prostate cancer, other cancer-related
      traits were examined (body mass index, PSA level, and alcohol drinking) with a
      number of known and potentially novel associations described. In general, these
      findings do not support there being many protein coding variants of moderate to
      high risk for breast and prostate cancer with odds ratios over a range that is
      probably required for protein coding variation to play a truly outstanding role
      in risk heritability. Very large sample sizes will be required to better define
      the role of rare and less penetrant coding variation in prostate and breast
      cancer disease genetics.

PMID- 23555317
TI  - Challenging controlling images, oppression, poverty and other structural
      constraints: Survival strategies among African American women in distressed
      households.
AB  - Powerful controlling images perpetuate misguided messages about impoverished
      African American women that contribute to the oppression these women endure.
      These images inform policies and behavior that create and maintain structural
      barriers such as lack of access to education and meaningful employment further
      marginalizing oppressed individuals. This article uses in-depth interview data to
      analyze interlocking oppressions in the lived experience of impoverished African
      American women. The authentic women's voices presented serve as a counter
      narrative of resistance. Our larger goal in writing this paper is to encourage
      the public, policy makers, service providers and impoverished African American
      women themselves to fight against controlling images by deconstructing personal
      biases, educating the public, and developing culturally congruent interventions
      to social problems.

PMID- 23555316
TI  - Coincident resection at both ends of random, gamma-induced double-strand breaks
      requires MRX (MRN), Sae2 (Ctp1), and Mre11-nuclease.
AB  - Resection is an early step in homology-directed recombinational repair (HDRR) of
      DNA double-strand breaks (DSBs). Resection enables strand invasion as well as
      reannealing following DNA synthesis across a DSB to assure efficient HDRR. While
      resection of only one end could result in genome instability, it has not been
      feasible to address events at both ends of a DSB, or to distinguish 1- versus 2
      end resections at random, radiation-induced "dirty" DSBs or even enzyme-induced
      "clean" DSBs. Previously, we quantitatively addressed resection and the role of
      Mre11/Rad50/Xrs2 complex (MRX) at random DSBs in circular chromosomes within
      budding yeast based on reduced pulsed-field gel electrophoretic mobility ("PFGE
      shift"). Here, we extend PFGE analysis to a second dimension and demonstrate
      unique patterns associated with 0-, 1-, and 2-end resections at DSBs, providing
      opportunities to examine coincidence of resection. In G2-arrested WT, Deltarad51
      and Deltarad52 cells deficient in late stages of HDRR, resection occurs at both
      ends of gamma-DSBs. However, for radiation-induced and I-SceI-induced DSBs, 1-end
      resections predominate in MRX (MRN) null mutants with or without Ku70.
      Surprisingly, Sae2 (Ctp1/CtIP) and Mre11 nuclease-deficient mutants have similar
      responses, although there is less impact on repair. Thus, we provide direct
      molecular characterization of coincident resection at random, radiation-induced
      DSBs and show that rapid and coincident initiation of resection at gamma-DSBs
      requires MRX, Sae2 protein, and Mre11 nuclease. Structural features of MRX
      complex are consistent with coincident resection being due to an ability to
      interact with both DSB ends to directly coordinate resection. Interestingly,
      coincident resection at clean I-SceI-induced breaks is much less dependent on
      Mre11 nuclease or Sae2, contrary to a strong dependence on MRX complex,
      suggesting different roles for these functions at "dirty" and clean DSB ends.
      These approaches apply to resection at other DSBs. Given evolutionary
      conservation, the observations are relevant to DNA repair in human cells.

PMID- 23555318
TI  - Spinal and extraspinal deformities in a patient with dysspondyloenchondromatosis.
AB  - Anisospondyly (irregularly shaped vertebral bodies) and enchondroma-like lesions
      in the metaphyseal and diaphyseal portions of the long tubular bones are the
      characteristic features in patients with dysspondyloenchondromatosis (DSC).
      Thoraco-lumbar scoliosis and windswept deformity of the lower limbs were the
      major abnormalities encountered in this patient. To the best of our knowledge
      this is the first case report delineating the spine pathology via reformatted CT
      scan and the correction of a windswept deformity by means of temporary
      hemiepiphysiodesis in a patient with (DSC).

PMID- 23555320
TI  - Protection of medical personnel in armed conflicts-case study: Afghanistan.
AB  - INTRODUCTION: International humanitarian law affords special protection to
      medical property and personnel whose mission is to save lives and provide health
      care for civilians and combatants alike. DISCUSSION: This paper presents the
      legal aspects of medical-personnel protection in armed conflicts. Presented below
      are examples of the Afghanistan analyses where, as a result of war situations,
      people are most vulnerable. Discussed are the minimum protection and standards
      applicable to such situations specified by the international humanitarian law.
      CONCLUSION: Its rules and provisions obligate fighting parties to take all
      necessary measures to protect and respect medical missions in all circumstances.

PMID- 23555321
TI  - Hodgkin's lymphoma in adults: diagnosis, treatment and follow-up.
AB  - BACKGROUND: With an incidence of 2 to 3 cases per 100 000 persons per year,
      Hodkgin's lymphoma (HL) is rare, but nonetheless one of the most common cancers
      in young adults. Improved treatment has made HL curable even in advanced stages,
      but controversy still surrounds a number of issues in patient care. Current
      research focuses on the avoidance of long-term adverse effects and secondary
      malignancies. METHODS: We selectively searched MEDLINE, CENTRAL, and the
      Guideline International Network for publications about HL. Two experts
      independently screened the retrieved publications for pertinence and extracted
      data from potentially relevant meta-analyses, randomized controlled trials
      (RCTs), and cohort studies into evidence tables. RESULTS: 32 key questions were
      answered with 160 recommendations on the basis of evidence from 43 RCTs, 21 meta
      analyses, and 119 cohort studies. Patients in an early stage of HL should be
      treated with two cycles of ABVD followed by involved-field radiotherapy (IF-RT)
      at a dose of 20 Gy (5-year overall survival [OS]: 94%). Patients in an
      intermediate (early unfavorable) stage should be treated with two cycles of
      BEACOPP escalated followed by two cycles of ABVD and 30 Gy IF-RT (5-year OS:
      97.2%). Patients in an advanced stage should be treated with six cycles of
      BEACOPP escalated, and the decision whether this should be followed by
      consolidating radiotherapy (30 Gy) should be based on the findings of positron
      emission tomography (radiate in case of PET-positive residual tumor; 5-year OS:
      95.3%). Depending on the treatment regimen, there may be adverse effects
      including infection, leukopenia, anemia, thrombocytopenia, secondary neoplasia,
      and fertility disorders. CONCLUSION: Most questions in the treatment of HL can
      now be answered on the basis of sufficient evidence from the literature. This
      holds in particular for the potential benefit to be gained from PET, follow-up
      care, and lifestyle recommendations for patients.

PMID- 23555319
TI  - Pathways to lifespan health following childhood parental death.
AB  - The death of a parent is a profoundly stressful form of childhood adversity,
      increasing the short- and long-term risk of mental health problems. Emerging
      research suggests it may also disrupt biological regulatory systems and increase
      the risk of long-term physical health problems. This article presents a
      theoretical framework of the process by which the experience of parental death
      during childhood may influence mental and physical health outcomes over time.
      Drawing from a broad literature on adaptation following childhood parental loss,
      we focus on risk and protective factors in the childhood environment that are
      theoretically and empirically linked to emotional and biological regulatory
      responses to stress later in life, the effects of which may accumulate to impact
      long-term health.

PMID- 23555323
TI  - Declaration of assumption of liability for all airlines.

PMID- 23555322
TI  - Human papilloma virus infection in head and neck cancer.
AB  - BACKGROUND: The causal link between cervical cancer and human papilloma virus
      (HPV) is well known. It is now becoming clear that some types of squamous-cell
      carcinoma of the head and neck, particularly oropharyngeal carcinoma (OPC), are
      also linked to HPV infection. The development of vaccines against certain HPV
      genotypes has changed the management strategy for HPV-associated diseases of the
      uterine cervix. An analogous approach is now being considered for the prevention
      of HPV-associated diseases of the head and neck. METHOD: We review pertinent
      articles retrieved by a selective search of the literature for phase II and III
      trials providing evidence about a possible effect of HPV status on the survival
      rates of patients with OPC. Seven trials fulfilled our search criteria: four
      phase III trials with retrospective HPV analysis and three phase II trials with
      retrospective and prospective HPV analysis. RESULTS: Patients with HPV-positive
      OPC survive significantly longer than those with HPV-negative OPC. Tobacco
      smoking has been identified as a negative prognostic factor in patients with
      either HPV-negative or HPV-positive disease. CONCLUSION: The established
      treatment strategy for OPC in patients with and without the traditional risk
      factors (tobacco and alcohol consumption) is now being reconsidered in the light
      of what we have learned about the role of HPV infection. Ongoing and projected
      clinical trials with risk-factor stratification may soon lead to changes in
      treatment. Further study is needed to answer the question whether HPV infection
      in the head and neck region is carcinogenic.

PMID- 23555324
TI  - Similar data collected.

PMID- 23555325
TI  - Risk of VTE is small but exists.

PMID- 23555326
TI  - In reply.

PMID- 23555327
TI  - Lucrative preterm babies.

PMID- 23555328
TI  - Lucrative preterm babies: in reply.

PMID- 23555329
TI  - Information based on knowledge-orientation alone has minimal effects in the long
      term.

PMID- 23555330
TI  - Simulated Red Blood Cell Motion in Microvessel Bifurcations: Effects of Cell-Cell
      Interactions on Cell Partitioning.
AB  - Partitioning of red blood cell (RBC) fluxes between the branches of a diverging
      microvessel bifurcation is generally not proportional to the flow rates, as RBCs
      preferentially enter the higher-flow branch. A two-dimensional model for RBC
      motion and deformation is used to investigate the effects of cell-cell mechanical
      interactions on RBC partitioning in bifurcations. The RBC membrane and cytoplasm
      are represented by sets of viscoelastic elements immersed in a low Reynolds
      number flow. Several types of two-cell interactions that can affect partitioning
      are found. In the most frequent interactions, a 'trade-off' occurs, in which a
      cell entering one branch causes a following cell to enter the other branch. Other
      types of interactions include 'herding,' where the leading cell is caused to
      enter the same branch as the following cell, and 'following,' where the trailing
      cell is caused to enter the same branch as the leading cell. The combined effect
      of these cell-cell interactions is a tendency towards more uniform partitioning,
      which results from the trade-off effect but is reduced by the herding and
      following effects. With increasing hematocrit, the frequency of interactions
      increases, and more uniform partitioning results. This prediction is consistent
      with experimental observations on how hematocrit affects RBC partitioning.

PMID- 23555331
TI  - Airway somatosensory deficits and dysphagia in Parkinson's disease.
AB  - BACKGROUND: Individuals with Parkinson's disease (PD) often experience
      substantial impairment of swallow control, and are typically unaware of the
      presence or severity of their impairments suggesting that these individuals may
      also experience airway sensory deficits. However, the degree to which impaired
      swallow function in PD may relate to airway sensory deficits has yet to be
      formally tested. OBJECTIVE: The purpose of this study was to examine whether
      airway sensory function is associated with swallow impairment in PD. METHODS:
      Eighteen PD participants and 18 healthy controls participated in this study and
      underwent endoscopic assessment of airway somatosensory function, endoscopic
      assessment of swallow function, and clinical ratings of swallow and disease
      severity. RESULTS: PD participants exhibited abnormal airway somatosensory
      function and greater swallow impairment compared with healthy controls. Swallow
      and sensory deficits in PD were correlated with disease severity. Moreover, PD
      participants reported similar self-rated swallow function as healthy controls,
      and swallow deficits were correlated with sensory function suggesting an
      association between impaired sensory function and poor self-awareness of swallow
      deficits in PD. CONCLUSIONS: These results suggest that control of swallow is
      influenced by airway somatosensory function, that swallow-related deficits in PD
      are related to abnormal somatosensation, and that swallow and airway sensory
      function may degrade as a function of disease severity. Therefore, the basal
      ganglia and related neural networks may play an important role to integrate
      airway sensory input for swallow-related motor control. Furthermore, the airway
      deficits observed in PD suggest a disintegration of swallow-related sensory and
      motor control.

PMID- 23555332
TI  - Takayasu arteritis: consideration of pulmonary involvement.

PMID- 23555333
TI  - Changing concept on vascular malformation: no longer enigma.

PMID- 23555334
TI  - Evolution of endovascular treatment for complex thoracic aortic disease.
AB  - In a relatively short period of time, transcatheter and endovascular approaches
      to treat thoracic aortic and structural heart disease have exploded onto the
      scene. New device frontiers already being forged in the experimental stages
      include expanded indications and variations of fenestrated and branch
      stentgrafting to treat thoracoabdominal and arch disease, endovascular ascending
      and aortic root repair, and all of the cardiac valves. A fundamental concept to
      optimize durability of endovascular repair is the need for fixation and seal in
      healthy tissue. Before long, the entire vascular and cardiovascular system will
      be within the reach of endovascular interventions. Ultimately, achieving success
      in this endeavor will require a combination of skill sets including familiarity
      with high definition imaging, surgical access, and the mastery of interventional
      techniques, as well as the development of better anatomy-specific and disease
      specific devices.

PMID- 23555335
TI  - Control of blood vessel identity: from embryo to adult.
AB  - Arteries and veins have been historically defined by the direction of blood flow
      and oxygen tension within the vessel, in addition to their functional,
      hemodynamic, and anatomical differences. It is now known that the molecular
      identity of these vessels is genetically predetermined, with specific molecular
      pathways activated during the development of arteries and veins. Eph-B4 is a
      determinant of venous differentiation and Ephrin-B2 is a determinant of arterial
      differentiation. Placement of a vein into the higher pressure and flow of the
      arterial circulation results in adaptation of the vein to the arterial
      environment. There is selective loss of Eph-B4 expression without induction of
      Ephrin-B2 expression during vein graft adaptation. These findings suggest that
      loss of venous identity is the crucial mechanism in vein graft adaptation and
      that developmentally critical determinants of vessel identity are plastic during
      adult life.

PMID- 23555336
TI  - Significance of the soleal vein and its drainage veins in cases of massive
      pulmonary thromboembolism.
AB  - In this report, we review the anatomical features of the crural veins and the
      importance of the soleal vein and its drainage veins for thrombi formation and
      propagation. The result of our investigation of 120 legs of 60 autopsy cases with
      fatal pulmonary thromboembolism showed that the soleal vein was the most frequent
      site of deep vein thrombosis, both for fresh and for organized thrombi.
      Furthermore, the detection rate of thrombi, both fresh and organized, showed that
      the most common site was in the soleal vein and then decreased progressively
      according to the drainage route of the soleal vein. Anatomical characteristics
      and physiological mechanisms play a major role in the occurrence and propagation
      of venous thrombi. Thus, an understanding of these features is essential for
      effective prophylaxis of venous thromboembolism.

PMID- 23555337
TI  - Hybrid treatment of multiple aortic aneurysms by combined conventional surgery
      and endovascular aortic repair.
AB  - PURPOSE: We evaluated the operative results of our treatment for multiple aortic
      aneurysms by means of a hybrid procedure consisting of a combination of
      conventional surgical maneuvers and simultaneous or sequential endovascular
      aortic repair (EVAR). MATERIALS AND METHODS: From August 1998 to April 2007, a
      total of 15 patients, 11 men and 4 women, ranging in age from 62 to 78 years,
      were treated with hybrid procedures for multiple aortic aneurysms. The pathology
      of these patients were, atherosclerotic aneurysm in 12 patients, atherosclerotic
      aneurysm associated with chronic dissection in 2 and type III chronic dissection
      in 1 patient. The distribution of aneurysmal locations were as follows: 5
      patients had aneurysms at the arch and descending aorta, 1 had at the arch and
      thoracoabdominal aorta, 6 at the descending and abdominal aorta. Two patients
      with chronic dissection had simultaneous abdominal aortic aneurysms. In all
      except 1 of the 7 patients who had abdominal aortic aneurysm, we performed
      abdominal aneurysmectomy and EVAR simultaneously. In 7 patients, EVAR was
      performed sequentially after graft replacement surgery. In 2 patients, EVAR was
      the initial procedure followed by conventional surgery. The mean interval between
      first and second stage procedures was approximately 4 months. RESULTS: One
      patients died of methicillin resistant Staphylococcus aureus pneumonia 3 months
      after the simultaneous procedure, all others were discharged and survive. In
      particular, no major EVAR linked complication was observed in the follow-up
      period (range 3 to 91 months, mean 46 months). CONCLUSION: The hybrid procedure
      for the treatment of multiple aortic aneurysmal disease is less invasive compared
      to conventional staged surgery and the outcome in terms of mortality and
      morbidity in hospital as well as long-term follow-up are satisfactory.

PMID- 23555338
TI  - Management of bilateral phlegmasia cerulea dolens in a patient with subacute
      splenic laceration.
AB  - Phlegmasia cerulea dolens (PCD) is a rare but limb-threatening complication of
      deep vein thrombosis. We report a case of a 76-year-old man with recent splenic
      trauma and inferior vena cava (IVC) filter placement, who developed bilateral
      lower extremity PCD. Utilizing an endoluminal approach, the patient underwent
      mechanical thrombectomy and thrombolysis through bilateral infusion catheters
      placed antegrade from bothpopliteal veins. Clot lysis and return of palpable
      pedal pulses occurred within 24 hours. We demonstrate that the endoluminal
      management of this disease may be cautiously applied to the trauma patient, and
      that the judicious use of thrombolytic therapy can be beneficial even in the
      patient with a high potential for hemorrhage.

PMID- 23555339
TI  - Superior mesenteric vein thrombosis in a patient with chronic inhalation exposure
      to stearic Acid.
AB  - A previously healthy 36-year-old man admitted via emergency room with complaint
      of progressive chronic abdominal pain for 2 weeks. An enhanced computed
      tomography (CT) scan revealed a total occlusion of the superior mesenteric vein
      with thrombus and partial thrombosis of main portal vein. However, CT scan did
      not show any evidence of infectious or inflammatory foci in the abdominal cavity.
      He did not have any family history of coagulation disorder. He neither had any
      detectable coagulation disorder to induce thrombosis. The only possible risk
      factor for the superior venous thrombus is chronic inhalation exposure to stearic
      acid.

PMID- 23555340
TI  - Aneurysms of gastroepiploic artery and vein with an arteriovenous fistula after
      partial gastrectomy in a patient presenting with abdominal aortic aneurysm-report
      of a case.
AB  - A case of asymptomatic right gastroepiploic artery and vein aneurysms with an
      arteriovenous (AV) fistula coexisting with an abdominal aortic aneurysm (AAA) is
      presented. A 68-year-old man was referred for treatment of AAA (6 cm in diameter)
      and he was incidentally diagnosed as having right gastroepiploic artery and
      venous aneurysms (3 cm and 8 cm in diameter, respectively) with an AV fistula.
      Resection of the aneurysms and closure of the fistula were successfully completed
      with AAA repair. He had a history of gastrectomy, and these gastroepiploic
      aneurysms with an AV fistula were considered a late complication due to mass
      ligation of vessels during gastrectomy.

PMID- 23555341
TI  - Buerger's Disease; Any Current Advances?

PMID- 23555343
TI  - Buerger disease, smoking, and periodontitis.
AB  - Weak oral bacteria such as periodontal bacteria or Chlamydia pneumoniae have been
      observed in various arterial and venous lesions with epidemiological data
      reported prior to the discovery of bacterial invasion into vessels. Rich lymph
      vessels easily bring the bacteria from the mouth to the neck and the venous
      angle, which is directly open to the blood vessels. Periodontal bacteria travel
      within platelets and Chlamydia pneumoniae can be carried by monocytes. The
      transportation system of other weak oral bacteria have not been determined.
      Periodontal bacteria, especially P. gingivalis aggregate platelets and form
      thrombi. At the same time, secretions such as serotonin, various cytokines, and
      adhesion factors also appear in the blood. The characteristics of arterial
      lesions are dependent on the age of the patient and the condition of the
      endothelial cells. In young patients, infectious incidents occur due to embolic
      mechanisms in Buerger disease or adhesion to the superficial veins valves in
      varicose veins. In older patients, incidents result in adhesion in the proximal
      aorta, coronary arteries, or large arteries. The hypothesis here unifies the
      evidence on vessel lesion development and explains the possible discrepancy
      between vascular diseases.

PMID- 23555342
TI  - Cell therapy for cardiovascular diseases.
AB  - There have been great progresses in our knowledge of patho-physiology on various
      cardiovascular diseases, which enabled us to develop the field of regenerative
      medicine for previously untreatable patients. Among several strategies in
      cardiovascular regenerative medicine, cell transplantation is one of the best
      studied and the best clinically practiced. In this review we will first summarize
      the mechanisms of cell therapy, and then go through lists of cells and diseases
      that can be applied. Later we will introduce some of the clinical experiences
      published so far, with some discussion regarding the problems and perspectives of
      this novel therapeutics.

PMID- 23555344
TI  - The Clinical Course of Buerger's Disease.
AB  - The clinical and social characteristics of 118 patients with Buerger's disease
      (thromboangiitis obliterans: TAO) were surveyed. The prognosis for many patients
      is relatively favorable. Arterial reconstruction plays a role in shortening the
      healing times of ischemic ulcers despite its poor long-term results. Of 118
      patients, 13 underwent major lower limb amputation (11%), 33 underwent foot or
      toe amputation (28%), one underwent hand amputation (1%), and 12 underwent finger
      amputations (10%) after the onset of the disease. The progression of symptoms was
      surely influenced by smoking, but this was not the only deleterious factor as
      there were patients with stable TAO which was unaffected by their continued
      smoking. In 66 patients, the new occurrence of ulceration and gangrene was not
      observed over the age of 60. Ten of 13 patients (77%) who underwent major lower
      limb amputation lost their jobs, but only 7 of 105 patients without major
      amputation lost their jobs (7%). In all patients, the progression of symptoms was
      self-limited and recurrent ulcers occurred less frequently with ageing. To avoid
      factors that markedly influence the quality of life, early treatment and strict
      instructions prohibiting smoking should be conducted.

PMID- 23555345
TI  - Endovascular treatment of venous occlusive disease.
AB  - Endovascular treatment of acute and chronic iliac vein occlusions has proven to
      be safe and effective. Recanalization of chronic occlusions with balloon
      angioplasty and stenting can re-establish normal venous flow in the iliac veins
      and the IVC and relieve symptoms in the majority of treated patients. CDT with
      recanalization and stenting of underlying chronically obstructed iliofemoral
      segments is becoming the treatment of choice for patients with acute iliofemoral
      thrombosis, as anticoagulation and compression therapy alone are not satisfactory
      in preventing PTS. The new treatment modalities offer stimulating options for a
      patient group that is not adequately treated, neither by medical nor open
      surgical therapy. The substantial effort and additional costs of endovascular
      treatment appear to be justified by the encouraging mid-term results both for
      patients with acute and chronic occlusive iliofemoral disease. However, multi
      center randomized prospective studies are required to further validate the role
      of these techniques.

PMID- 23555346
TI  - Effects of the 5-HT2A Antagonist Sarpogrelate on Walking Ability in Patients with
      Intermittent Claudication as Measured Using the Walking Impairment Questionnaire.
AB  - BACKGROUND: The Walking Impairment Questionnaire (WIQ) measures walking ability
      in daily life in patients with peripheral arterial disease causing intermittent
      claudication. We investigated the efficacy of sarpogrelate, a 5-HT2A receptor
      antagonist, in improving walking ability, as measured using new Japanese version
      of the WIQ. PATIENTS AND METHODS: A nationwide multicenter study was conducted at
      80 institutions in Japan involving 586 patients with stable symptoms of
      intermittent claudication. Patients received open-label sarpogrelate 300 mg/day.
      A total of 419 patients were evaluated in the full analysis set (FAS) following
      the intention to treat principle, and 354 patients were evaluated in the per
      protocol set (PPS). The FAS data are emphasized here. RESULTS: The mean follow-up
      was 27.7 +/- 10.1 weeks. Each subscale of the WIQ score showed improvement after
      sarpogrelate treatment (p < 0.0001), and the resting ankle-brachial index
      increased significantly (p < 0.0001). The incidence of adverse reactions of the
      entire series of 559 patients was 4.83% (27 patients), but there were no
      clinically significant safety concerns. CONCLUSIONS: We have for the first time
      demonstrated that sarpogrelate may improve walking ability in daily life in
      Japanese patients with intermittent claudication. The drug had a good safety
      profile.

PMID- 23555347
TI  - Immersing Feet in Carbon Dioxide-enriched Water Prevents Expansion and Formation
      of Ischemic Ulcers after Surgical Revascularization in Diabetic Patients with
      Critical Limb Ischemia.
AB  - OBJECTIVE: We investigated the effect of immersion of feet in CO2-enriched water
      for preventing expansion and formation of ischemic ulcer in critical limb
      ischemia of diabetic patients after surgical revascularization. MATERIALS AND
      METHODS: Eligible patients were allocated CO2 group (CO2 immersion plus standard
      care) or control group (standard care alone) and were followed up for 3 months
      after surgical revascularization. The end point is defined as an expansion of a
      target ulcer (more than 101% of original size) or the formation of new ulcers
      during the follow-up period. RESULTS: Fifty-nine patients out of originally
      enrolled 66 patients with type II diabetes were included in intention-to-treat
      population. The cumulative prevention rate for ischemic ulcer after 3 months was
      97.1% in the CO2 group, while, in the control group, it was 77.8%, i.e.,
      significantly lower than the CO2 group (P = 0.012, log-rank test). The
      transcutaneous oxygen pressure increased significantly only in the CO2 group,
      from 56 +/- 14 to 63 +/- 15 mmHg (P < 0.01, Wilcoxon signed rank test), in 3
      months. CONCLUSION: These results suggest that addition of CO2 immersion to
      standard care of critical limb ischemia in diabetic patients improves early
      postoperative outcome after vascular surgery.

PMID- 23555348
TI  - Type I Endoleak-like Phenomenon Causing Rupture of the Replaced Aneurysm Sac 12
      Years after Open Repair of Abdominal Aortic Aneurysm.
AB  - Only a few cases of endoleak following conventional abdominal aortic aneurysm
      repair have been reported. We treated a patient with a type I endoleak-like
      phenomenon occuring 12 years after conventional abdominal aortic aneurysm repair.
      Computed tomography demonstrated dilation of the surgically replaced, once
      shrunken aneurysm sac to a diameter of 3.5 cm. Thrombus was identified between
      the graft and the sac. Four months later the sac ruptured, and emergency repair
      was performed. Dehiscence of the proximal anastomosis causing dilation and
      tearing of the sac was found. Dilation of a surgically replaced aneurysm sac
      after initial shrinkage may suggest an endoleak-like phenomenon requiring second
      repair.

PMID- 23555350
TI  - Percutaneous cardiopulmonary support for the treatment of acute pulmonary
      embolism: summarized review of the literature in Japan including our own
      experience.
AB  - BACKGROUND: Acute pulmonary embolism (APE) has high mortality. Some APEs with
      circulatory collapse or cardiopulmonary arrest have been treated by percutaneous
      cardiopulmonary support (PCPS) in Japan. But there have been no reports with a
      large number of series of APE treated with the use of PCPS. METHODS AND RESULTS:
      We collected all the reported cases with acute thrombotic pulmonary embolism
      treated with PCPS before surgical embolectomy or those without surgical
      embolectomy in Japan, and assessed the effectiveness of PCPS. PCPS was combined
      with surgical embolectomy in 35% (68 of 193), thrombolytic therapy in 62%
      (120/193), and catheter therapy in 24% (46/193). The survival rate treated with
      PCPS was 73% (80% in surgical embolectomy, 71% in thrombolytic therapy, and 76%
      in catheter therapy). Logistic regression analysis showed that the mortality rate
      was elevated in cases with cardiopulmonary arrest (odds ratio [OR], 3.41; 95%
      confidence interval [CI], 1.52-7.67; p-value, 0.003) but not by surgical
      embolectomy (OR, 0.99; 95% CI, 0.39-2.53; p-value, 0.98), catheter therapy (OR,
      0.71; 95% CI, 0.30-1.72; p-value, 0.45), and thrombolysis (OR, 1.60; 95% CI, 0.64
      3.99; p-value, 0.31) as regards to the concomitant therapies with PCPS.
      CONCLUSION: PCPS might improve the survival rate in APE patients with circulatory
      collapse or cardiopulmonary arrest, but there was no differences in outcome among
      cases treated by surgical embolectomy, catheter therapy, and thrombolysis as the
      concomitant therapies.

PMID- 23555351
TI  - Medical standards seen from the perspective of changes in academic society
      themes: investigation of a lawsuit concerning the prevention of venous
      thromboembolism.
AB  - OBJECTIVE: To determine whether a violation of the standard of care for
      prevention of pulmonary embolism by preventing deep vein thrombosis occurred in
      1999. MATERIALS AND METHODS: Themes from past general meetings of the three
      societies that comprise the Japanese Board of Cardiovascular Surgery that
      pertained to venous thromboembolism from 1999 to 2006 were examined and analyzed
      for an appeal hearing to determine whether a violation had occurred. RESULTS: The
      first pertinent session on a method for the prevention of pulmonary embolism was
      presented in 2006 by the Japanese Society for Vascular Surgery. Thus, the medical
      treatment performed in this case did not violate the standard of care in 1999.
      CONCLUSION: The "standard of medical treatment at the time", can be discerned by
      tracing consensus agreement at session meetings. If the consensus from each
      session is recorded, a more detailed analysis can be made of the agreement
      reached by board members.

PMID- 23555352
TI  - Skin Perfusion Pressure is a Useful Tool for Evaluating Outcome of Ischemic Foot
      Ulcers with Conservative Therapy.
AB  - OBJECTIVES: This study intended to confirm whether skin perfusion pressure (SPP)
      could predict the outcome of ischemic wound healing. PATIENTS AND METHODS: Sixty
      two limbs in 53 patients with conservative therapy were enrolled in this study. A
      SPP value of 40 mmHg was adopted as the criterion for making clinical decisions.
      The outcome one month after SPP measurement was classified as "improved"
      (diameter of ulcer decreased >= 20% or demarcation of gangrene became well
      defined) or "no change or worse" (others), and the fate of wound was classified
      as "healed" or "not healed". The evaluated influential factors on the outcome at
      one month included age, sex, presence of arteriosclerosis obliterans, collagen
      disease, hypertension, diabetes mellitus, hemodialysis, wound infection, wound
      management, and SPP >= 40 mmHg. RESULTS: Using a criterion of SPP >= 40 mmHg, the
      outcome at one month could be predicted with a sensitivity: of 75.0%, a
      specificity: of 82.6%, and an accuracy: of 80.6%. The receiver operating
      characteristic curve indicated our criterion to be appropriate. Logistic
      regression analysis showed SPP >= 40 mmHg to be an independent factor (P <
      0.0001) with the odds ratio of 14.2 (95% CI 3.6-55.8). CONCLUSIONS: SPP, using a
      cutoff value of 40 mmHg, can predict the ischemic wound healing with conservative
      therapy.

PMID- 23555353
TI  - Intravascular Ultrasound Analysis of Correlation between Plaque-Morphology and
      Risk Factors in Peripheral Arterial Disease.
AB  - OBJECTIVE: To analyze relationships between plaque-morphology classified by
      intravascular ultrasound (IVUS) and risk factors in patients with peripheral
      arterial disease (PAD). METHODS: We performed IVUS in 203 patients with PAD.
      Multiple regression and logistic analysis were used to assess relationships
      between plaque-morphology (degree of calcification, presence of a lipid core,
      intimal flap and thrombus) and risk factors including diabetes mellitus,
      hypertension, dyslipidemia, estimated glomerular filtration rate (eGFR), HbA1c
      and the homeostasis model assessment-insulin resistance ratio (HOMA-IR). RESULTS:
      IVUS data led to 22% of lesions being classified as soft, 18% as fibrous, 32% as
      calcified, and 28% as mixed. Calcification was present in the superficial and
      deep layers in 65% and 35% of cases, respectively, and a lipid core, intimal flap
      and thrombus were found in 31%, 5.4% and 3.0%, respectively. The calcified angle
      correlated with HbA1c and eGFR (p < 0.05). Associations were found between deep
      calcification and HOMA-IR (odds ratio: 4.4, p < 0.05) and a lipid core and
      hypercholesterolemia (odds ratio: 3.2, p < 0.05). The odds ratio for intimal flap
      was 15.6 times with hypercholesterolemia (p < 0.05) and 16.9 times with a high
      HOMA-IR (p < 0.01). CONCLUSION: Plaque calcification and morphology are
      associated with chronic kidney disease, insulin resistance and dyslipidemia in
      PAD patients.

PMID- 23555354
TI  - Early Experiences of Laparoscopic Aortofemoral Bypass in Korea-report from a
      Single Center.
AB  - Although endovascular approach can be widely applied to occlusive aortoiliac
      segment, aortofemoral bypass (AFB) continues to offer superior long term patency.
      In an effort to reduce the morbidity of AFB, LAFB (laparoscopic AFB) has been
      developed. We report our initial experiences to determine the feasibility and
      safety. From September 2005 to May 2008, LAFB was performed in 12 patients. A
      transabdominal retrocolic approach with pneumoperitoneum or direct approach was
      preferred. LAFB consisted of aortic dissection, vascular control with or without
      intracorporeal anastomosis. Last two cases were performed using da Vinci system
      for secure proximal anastomosis as an end to side fashion. Laparoscopic
      procedures were successfully performed in 11 patients. One patient underwent open
      conversion due to small bowel injury and bleeding. Mean operating time and aortic
      clamping time was 446 minutes and 87.5 minutes. The time to return of bowel
      function was about 2.1 days (2.1 +/- 1.2). Compartment syndrome was developed in
      one patient at immediate postoperatively. During this study period, operating
      time was shown in decreasing tendency. Although LAFB is challenging procedure
      with steep learning curve, it is feasible technique and appears to ease patient's
      postoperative course.

PMID- 23555355
TI  - Retrieval of gunther tulip vena cava filter with thrombosed hook and a leg
      incorporated into the vena cava wall.
AB  - A Gunther tulip vena cava filter was implanted in a patient with pulmonary
      embolism from deep venous thrombosis. The filter became unnecessary after
      therapy. However, retrieval by the standard method employing a vascular sheath
      placed via the transjugular approach in combination with a snare device was
      impossible. A thrombus occupying the apical hook made it difficult to snare the
      hook, also one filter leg was incorporated into the inferior vena cava wall.
      Therefore we modified an existing method to withdraw the filter. As the first
      step, the filter cone was snared using the snare-over-guide wire loop technique,
      and the cephalad site of the filter was introduced into the sheath. Then, a 12
      French sheath was advanced from the femoral vein and, using a pusher, the distal
      legs of the filter were pushed, which resulted the filter leg that was
      incorporated into the inferior vena cava wall became detached. Finally the filter
      was successfully retrieved.

PMID- 23555356
TI  - Perigraft seroma after surgical aortoiliac aneurysm repair with knitted polyester
      grafts: report of two cases.
AB  - Perigraft seroma usually occurs both polyester and polytetrafluoroethylene (PTFE)
      graft which are placed superficially for axillofemoral and femorofemoral
      bypasses, while it is a rare complication of conventional abdominal aortic and
      iliac arterial aneurysm repair. The cause of the seroma has not been elucidated,
      and several hypotheses have been proposed such as immunologic response to graft
      materials, discharge of serous fluid through the graft wall, and so on. The
      seroma sac occasionally increases their size finally leading to rupture. The
      treatment of perigraft seroma has not been established so far; there have been
      various recommended procedures including aspiration, graft removal followed by
      other material graft replacement, cessation of antithrombotic drugs, and careful
      observation. We report two cases of perigraft seroma after conventional
      aortoiliac aneurysm repair with a knitted polyester graft via left pararectal
      retroperitoneal approach, which were gradually shrinking by theirselves.

PMID- 23555357
TI  - Two-stage Surgery for Endovascular Repair and Laparoscopic Colectomy for a
      Patient with Abdominal Aortic Aneurysm and Concomitant Colon Cancer: Report of a
      Case.
AB  - Surgical management of abdominal aortic aneurysm (AAA) with concomitant
      malignancy remains controversial. Commercial availability of a stentgraft may
      change the treatment strategy for such patients. We present a case of AAA with
      concomitant colon cancer, in which two-stage surgery consisting of EVAR and
      subsequent laparoscopic colectomy was performed with an interval of six days. The
      patient's postoperative course was uneventful. For high-risk patients,
      application of endovascular AAA repair and laparoscopic surgery may decrease the
      risk of surgical morbidity and mortality.

PMID- 23555358
TI  - Migration of distal ventriculoperitoneal shunt catheter into the pulmonary
      artery.
AB  - A 50-year-old man presented with an abdominal bulge 2 years after receiving a
      ventriculoperitoneal (VP) shunt for hydrocephalus. Chest radiography revealed
      that the peritoneal end of the catheter had migrated into the right pulmonary
      artery. Exploration through a small neck incision revealed that the shunt
      catheter had entered the internal jugular vein. The catheter was extracted and
      positioned in the subcutaneous space in preparation for reimplantation. This type
      of shunt migration is quite unusual, but it could cause lethal pulmonary
      infarction or arrhythmia. Follow-up radiography should be scheduled to detect
      such complications.

PMID- 23555359
TI  - Endovascular Repair of a Kommerell's Diverticulum and Aneurysmal Right-sided
      Aortic Arch: A Case Report.
AB  - Right-sided aortic arch with aberrant left subclavian artery is an uncommon
      anomaly. We describe a case of Kommerell's diverticulum involving the distal
      portion of a right-sided aortic arch and the origin of an aberrant left
      subclavian artery in a 74-year-old man with hoarseness. The patient underwent
      successful endovascular repair of the aneurysm with use of a Gore TAG thoracic
      endoprosthesis and coil embolization of the left subclavian artery. Postoperative
      computed tomography showed complete exclusion of the lesion, without endoleaks.
      Endovascular repair is feasible and can be effective in such cases.

PMID- 23555360
TI  - Successful surgical treatment for rupture of an iliac artery aneurysm into a
      ureter.
AB  - We describe a case of successful surgical treatment for spontaneous rupture of an
      iliac artery aneurysm into a ureter. An 80-year-old man was admitted with massive
      hematuria. Immediate enhanced abdominal computed tomography scan and cystoscopy
      were suspicious for a uretero-arterial fistula caused by aneurysmal rupture.
      Emergent surgical intervention was performed because of the high mortality rate
      of this condition. Intraoperative findings revealed the fistula between the true
      aneurysm of the right common iliac artery and the ureter. Repair of the aneurysm
      and ligation of the ureter was performed, with an uneventful postoperative
      course.

PMID- 23555361
TI  - Clinical Usefulness of Hybrid Intervention for the Treatment of Primary
      Thrombosis of Axillary-subclavian Vein.
AB  - Untreated symptomatic patients with Paget-Schroetter syndrome can suffer chronic
      disability due to venous obstruction, with arm swelling, pain, and early exercise
      fatigue. Although systemic or catheter-directed thrombolysis followed by
      anticoagulation and surgical intervention is recommended, there is no definite
      consensus about treatment. Here, we report the clinical usefulness of hybrid
      intervention with a combination of thrombectomy, thrombo-aspiration and balloon
      PTA, which has not been reported previously for this condition. These procedures
      were successful, and the patient has been free of symptoms for 6 years.

PMID- 23555362
TI  - A case of ruptured aneurysm of the persistent sciatic artery presenting acute
      lower limb ischemia.
AB  - Only 5 cases of ruptured aneurysm of the persistent sciatic artery have been
      previously reported to date. We experienced a case of ruptured aneurysm of the
      persistent sciatic artery presenting acute lower limb ischemia. Physical
      examination showed a pulsatile mass with a subcutaneous hemorrhage in the left
      buttock, drop foot and paresthesia of the foot due to limb ischemia. An enhanced
      computed tomography scan showed a ruptured aneurysm of the left persistent
      sciatic artery at the level of the greater trochanter. An exclusion of the
      aneurysm and creation of common iliac to popliteal artery bypass was performed as
      an emergency operation.

PMID- 23555365
TI  - (1) coronary events caused by myocardial bridge.
AB  - Myocardial bridge (MB), which covers a part of the left anterior descending
      coronary artery (LAD), is a normal anatomical variant structure (45% in frequency
      by autopsy) in LAD. MB contraction plays the role of a "double-edged sword" on
      the coronary events, suppressing coronary atherosclerosis under the MB, yet
      generating abnormal blood flow associated with coronary heart diseases (CHDs).
      High shear stress driven by MB compression causes the suppression of vascular
      permeability and vasoactive protein expression such as e-NOS and endothelin-1,
      which leads to the suppression of atherosclerosis in the LAD segment under the
      MB. However, despite the prevalent view of MB as benignancy by conventional
      coronary angiography (5-6% in frequency), with advance of imaging technique such
      as multislice spiral computed tomography [(MSCT); 16% in frequency],
      cardiologists are now frequently aware of symptomatic MB occurring not only in
      hospitalized patients, but also in young athletes free from atherosclerosis.
      Moreover, the large mass volume of MB muscle induces atherosclerosis evolution at
      the settled site in LAD proximal to MB and contributes to the occurrence of
      myocardial infarction. These events upon the coronary events result from the
      different pathophysiological mechanisms induced by contractile force of MB, which
      is solely determined just by the integration of anatomical properties of MB, such
      as the location, length and thickness of MB in an individual LAD. A recent MSCT
      provides the objective quantification of the anatomical variables that correlate
      with the histopathological results in relation to the occurrence of CHD. In this
      review, we therefore discuss the necessity to explore MB as a inherent chance
      anatomical risk factor for CHD.

PMID- 23555366
TI  - Open treatment versus endovascular repair for aortic abdominal aneurysm-keeping
      the balance.

PMID- 23555367
TI  - Effects of antiplatelet agents and other factors on neointimal proliferation in
      iliac artery stenting: intravascular ultrasound analysis.
AB  - OBJECTIVE: To use intravascular ultrasound to investigate the effects of
      antiplatelet agents and other factors on neointimal proliferation after stent
      implantation for iliac artery stenosis. PATIENTS AND METHODS: The subjects were
      109 patients with peripheral arterial disease who underwent stent implantation in
      the iliac artery. Intravascular ultrasound was performed to evaluate lesion area,
      stent dilatation and neointimal proliferation before, just after, and six months
      after stenting. Multiple regression analysis was performed to examine the
      relationship of the neointimal proliferation rate with antiplatelet agents and
      other factors. RESULTS: At the time of stent implantation, a Palmaz stent
      resulted in a significant increase in lumen area compared with a Wallstent (p <
      0.05). Six months later, self-expanding Wallstent and Luminexx stents showed a
      significant increase in the stent-lumen area (p < 0.05). The neointimal
      proliferation rate showed a significant negative correlation with beraprost and
      cilostazol (p < 0.05) and a significant positive correlation with serum
      creatinine (p < 0.01). There was no significant difference in the vessel lumen
      area including the proliferated intima among the three stents. CONCLUSION:
      Suppression of neointimal proliferation can be achieved with beraprost or
      cilostazol whereas renal dysfunction may increase neointimal proliferation
      following stent implantation in iliac artery lesions.

PMID- 23555368
TI  - Efficacy of Elective Intra-aortic Balloon Pump Therapy for High-Risk Off-Pump
      Coronary Artery Bypass: A Prospective Comparative Study.
AB  - OBJECTIVE: This study evaluated the usefulness of elective intra-aortic balloon
      pumping (IABP) in high-risk off-pump coronary artery bypass grafting (OPCAB).
      MATERIALS AND METHODS: From October 2002 through September 2006, total of 143
      patients were operated with OPCAB. These patients were divided into two groups
      and clinical outcomes were compared: Group E (N = 30): Elective IABP group and
      Group C (N = 113): Control group, OPCAB without IABP. The criteria of elective
      application of IABP were severe stenosis of left main coronary artery (LMCA) or
      left ventricular dysfunction with an ejection fraction of less than 35%. RESULTS:
      No significant difference was noted in the duration of ICU stay (Group E: 1.13 +/
      0.43 days; Group C: 1.18 +/- 0.60 days, p = 0.710), the number of patients on a
      respirator for 24 hours or longer after surgery (Group E: 10.0%; Group C: 5.3%, p
      = 0.397), hospital mortality (Group E: 0%; Group C: 0%), or the frequency of
      postoperative major complications between two groups. CONCLUSIONS: The outcomes
      of OPCAB using elective IABP in high-risk patients, such as those with severe
      LMCA stenosis or left ventricular dysfunction, were similar to those of OPCAB in
      low-risk patients, suggesting the usefulness of elective IABP in OPCAB.

PMID- 23555369
TI  - A case of successful treatment of acute iliofemoral venous thrombosis caused by
      giant myoma through combination of simultaneous hysterectomy and thrombectomy.
AB  - A 42-year-old woman complained of a sudden swelling and pain in her left lower
      extremity. Her lower abdomen was distended, and the thrombosis of iliac vein
      caused by giant myoma was detected by magnetic resonance imaging. A laparotomy
      was performed under general anesthesia with positive-pressure ventilation,
      anterior total hysterectomy and thrombectomy of iliofemoral vein simultaneously
      were performed. A postoperative venography revealed excellent recanalization of
      iliofemoral vein and she was subsequently discharged from hospital. Her clinical
      course has been extremely good, with no symptoms of post-thrombotic syndrome for
      two years.

PMID- 23555370
TI  - Vasculo-Behcet's Disease that Began with Femoral Arterial Pseudoaneurysm Followed
      by Deep Venous Thrombosis: Report of a Case.
AB  - Vasculo-Behcet's disease mainly affects the venous system and central or
      peripheral arteries. It is often difficult to diagnosis this due to the
      complexity of symptoms and the rarity. A 35-year-old man with refractory inguinal
      lymphadenitis was admitted to our hospital. He was diagnosed with left femoral
      arterial pseudoaneurysm by enhanced CT scan of the lower legs, and we performed
      an emergency operation. Seven months postoperatively, he suddenly developed deep
      venous thrombosis, and then, symptoms such as aphthous stomatitis and pudendal
      ulcer started to develop progressively, complicating his uveitis. Finally, he was
      diagnosed with vasculo-Behcet's disease.

PMID- 23555372
TI  - Chronic thromboembolic pulmonary hypertension.

PMID- 23555371
TI  - An Unusual Complication of EVAR, Spontaneous Rectus Sheath Hematoma: A Case
      Report.
AB  - OBJECTIVE: To report a successful conservative management in a case of
      spontaneous rectus sheath hematoma (SRSH) after Endovascular Aneurysmal Repair
      (EVAR) of infrarenal Abdominal Aortic Aneurysm (AAA). CASE PRESENTATION: An 84
      year-old woman with a 6 cm in diameter infrarenal AAA underwent EVAR at our
      hospital. During the procedure, intravenous heparin was administered to keep the
      activated clotting time around 300 seconds. One hour after the procedure, the
      patient complained of pain on her right side abdomen. Physical examination
      revealed a tender mass in the right lower abdominal wall. Laboratory studies
      showed a fall in hemoglobin from 12.7 g/dl to 9.3 g/dl. Ultrasound (US)
      examination demonstrated an 8 * 5 cm hematoma within the right rectus muscle.
      Follow-up US examination revealed that the hematoma had enlarged and a computed
      tomography (CT) examination of the lower abdomen was performed. CT scan showed a
      smooth-shaped mass within the layers of the anterolateral abdominal wall leading
      to enlargement of the right rectus abdominis muscle without signs of active
      bleeding. A conservative management was considered. RESULT: The clinical course
      was uneventful with a stable hemodynamic state. The patient was discharged 12
      days later and was doing well at the 2 week follow-up. CONCLUSION: Spontaneous
      rectus sheath hematoma is an unusual complication of a patient on anticoagulant
      therapy during EVAR. A prompt radiological investigation may prevent unnecessary
      surgical procedures in this unusual complication.

PMID- 23555373
TI  - Diagnosis and vasculopathy in chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by
      pulmonary hypertension caused by nonresolving thromboemboli of the pulmonary
      artery. However, up to 40% of CTEPH patients have had no clinically apparent
      acute pulmonary embolic episodes. In addition, both a female predominance and an
      association of HLA with CTEPH unrelated to deep vein thrombosis are observed in
      Japan, thus suggesting this condition to be a type of pulmonary vasculopathy. The
      key for making an accurate diagnosis is to consider CTEPH in any patients with
      dyspnea on exertion. Perfusion scans provide an excellent noninvasive tool for
      distinguishing between pulmonary arterial hypertension (PAH) and CTEPH, while CT
      angiography is useful for differentiating arteritis, tumor, and a congenital
      anomaly of the pulmonary artery from CTEPH. Pulmonary angiography (PAG) is still
      considered the gold standard for evaluating CTEPH. No subpleural perfusion in any
      segments by PAG with high pulmonary vascular resistance is might be related to
      small vessel disease, thus resulting in a poor outcome after surgery. Recent data
      suggest a potential therapeutic benefit of antiproliferative therapy for cells
      isolated from endarterectomized tissue.

PMID- 23555374
TI  - Circulatory assistance and surgery for residual pulmonary hypertension following
      thromboendarterectomy.

PMID- 23555375
TI  - A Randomized Controlled Study to Compare the Effects of Rosuvastatin 2.5 mg and
      Pravastatin 10 mg on the Plasma Lipid Profile in Japanese Patients with
      Hypercholesterolemia (ASTRO-1).
AB  - OBJECTIVE: For new evidence of treatment with statins in Japanese
      hypercholesterolemic patients, we performed an open-label, randomized, parallel
      group comparative study to assess the effect of rosuvastatin 2.5 mg and
      pravastatin 10 mg on plasma lipids. METHODS: A total of 100 patients in whom the
      target control levels of LDL-cholesterol (LDL-C) set by the Japan Atherosclerosis
      Society Guidelines (JASGL2007) had not been achieved were randomly assigned to
      receive rosuvastatin 2.5 mg / day or pravastatin 10 mg / day for 8 weeks. The
      primary endpoint was the percent change of LDL-C at week 8. RESULTS: LDL-C was
      lowered by -40.3% (from 160.3 to 95.1 mg / dL) in the rosuvastatin group and 
      22.9% (from 162.9 to 126.0 mg / dL) in the pravastatin group, at week 8 (P <
      0.001 vs. pravastatin). LDL-C / HDL-C ratio was lowered by -41.3% (from 2.85 to
      1.69) and -20.6% (from 2.81 to 2.24), respectively (P < 0.001 vs. pravastatin).
      The rate of achievement of the target LDL-C control level at week 8 was
      significantly higher in the rosuvastatin group (98.0%) than in the pravastain
      group (78.7%) (P = 0.003). Both drugs were well tolerated. CONCLUSION:
      Rosuvastatin 2.5 mg produced significantly greater reduction in LDL-C and
      beneficial effect on other lipid parameters than pravastatin 10 mg, and its
      safety profile is similar to pravastatin 10 mg.

PMID- 23555376
TI  - A Randomized Controlled Study to Compare the Effects of Rosuvastatin 5 mg and
      Atorvastatin 10 mg on the Plasma Lipid Profile in Japanese Patients with
      Hypercholesterolemia (ASTRO-2).
AB  - OBJECTIVE: For new evidence of aggressive lipid lowering treatment with statins
      in Japanese hypercholesterolemic patients, we performed an open-label,
      randomized, parallel-group comparative study to assess the effect of rosuvastatin
      5 mg and atorvastatin 10 mg on plasma lipids. METHODS: A total of 900 patients in
      whom the target control levels of LDL-cholesterol (LDL-C) set by the Japan
      Atherosclerosis Society Guidelines (JASGL2007) had not been achieved were
      randomly assigned to receive rosuvastatin 5 mg / day (n = 450) or atorvastatin 10
      mg / day (n = 450) for 8 weeks. The primary endpoint was the percent change of
      LDL-C at week 8. RESULTS: LDL-C was lowered by -44.5% (from 170.2 to 93.3 mg /
      dL) in the rosuvastatin group and -41.6% (from 169.5 to 97.9 mg / dL) in the
      atorvastatin group, at week 8 (P = 0.002 vs. atorvastatin). LDL-C / HDL-C ratio
      was lowered by -47.6% (from 3.01 to 1.56) and -43.5 % (from 2.96 to 1.66),
      respectively, at week 8 (P < 0.001 vs. atorvastatin). The changes in HDL-C, ApoB,
      ApoA-1, and ApoB / ApoA-1 ratio showed significant improvement in the
      rosuvastatin group than in the atorvastatin group. Adverse events were observed
      comparably between the rosuvastatin group (121 events) and the atorvastatin group
      (104 events). None of these events had adverse clinical consequence. Both drugs
      were well tolerated. CONCLUSION: Rosuvastatin 5 mg produced significantly greater
      reduction in LDL-C and beneficial effect on other lipid parameters than
      atorvastatin 10 mg, and was also well tolerated.

PMID- 23555377
TI  - A New Extra-anatomical Bypass for Atypical Aortic Coarctation with Porcelain
      Aorta: Reno-iliac Arterial Bypass.
AB  - We report a case of atypical aortic coarctation with severe calcification of the
      proximal aorta treated by a new extra-anatomical bypass. This 58-year-old woman
      with coarctation of the infrarenal aorta had thick circular calcifications of the
      thoracic aorta and stenosis of the subclavian arteries. To control the
      progressive claudication, we performed a bypass with an externally supported PTFE
      graft 6mm in diameter between the right renal artery and the right common iliac
      artery. Postoperative ankle pressure rose to 84 mmHg (right) and 89 mmHg (left)
      from zero, and she could walk without pain. Renal function was preserved. Using
      the proximal anastomosis from the non-diseased aortic branch to avoid the
      calcified aorta, reno-iliac arterial bypass is a useful alternative for control
      of ischemic lower limbs.

PMID- 23555378
TI  - Deep vein thrombosis associated with femur osteochondroma: report of a case.
AB  - The predisposing condition of deep vein thrombosis (DVT) is venous stasis or
      hypercoagulable state. Impaired venous blood flow caused by extrinsic compression
      is relatively rare situation. Only 3 cases of deep vein thrombosis due to
      osteochondroma have previously been reported in English literature. We report a
      case of a 21-year-old man, who presented with left lower leg pain and swelling
      due to extrinsic compression of femoral vein by an osteochondroma. In the case of
      vascular complications due to an osteochondroma, prompt surgical intervention
      should be made to avoid irreversible vein wall damages.

PMID- 23555379
TI  - Acute submassive pulmonary embolism following varicose vein surgery in a patient
      receiving hormonal replacement therapy.
AB  - Acute pulmonary embolism following varicose vein surgery is reported in a patient
      receiving hormonal replacement therapy. A 45-year-old woman underwent partial
      stripping of the greater saphenous vein of her bilateral legs and division of the
      lesser saphenous vein of her left legs under spinal anesthesia. On the first
      postoperative day, she complained of severe chest discomfort and collapsed
      suddenly while walking to the toilet. Emergency spiral computed tomography and
      perfusion scintigraphy demonstrated multiple defects in the bilateral lower
      lobes. She recovered after aggressive anticoagulant therapy. Although acute
      pulmonary embolism occurs only rarely after varicose vein surgery, it is
      important to remember its possibility especially when a patient has known risk
      factors predisposing venous thromboembolism, such as hormone replacement therapy.

PMID- 23555380
TI  - Bilateral radial artery aneurysms in the anatomical snuff box seen in marfan
      syndrome patient: case report and literature review.
AB  - We describe the first Marfan syndrome case of non-traumatic bilateral radial
      artery aneurysms in the anatomical snuff box. A 74-year-old woman with Marfan
      syndrome had a pulsatile mass in her bilateral anatomical snuff box. The color
      Doppler ultrasonography showed an aneurysm of radial artery located in the
      bilateral anatomical snuff box. Resection of the right radial artery aneurysm was
      completed without complications. Histopathological analysis showed a true
      aneurysm with atherosclerotic changes in the arterial wall. We review the
      literature on non-traumatic or bilateral radial artery aneurysm in the anatomical
      snuff box, and discuss the clinical presentation and surgical management.

PMID- 23555381
TI  - Emergency endovascular repair of a ruptured descending thoracic aortic aneurysm
      in an octogenarian: report of a case.
AB  - Emergency conventional surgical repair of the descending thoracic aorta remains a
      therapeutic challenge and is associated with a high risk of mortality. We
      describe a case of ruptured descending thoracic aortic aneurysm in an 87-year-old
      man who presented with chest and back pain. The patient underwent successful
      endovascular repair of the lesion with the use of Gore TAG thoracic
      endoprosthesis. Post-procedure computed tomography showed complete exclusion of
      the aneurysm without endoleaks. Endovascular repair is feasible and can be
      effective in such cases.

PMID- 23555382
TI  - Infected aneurysm: current management.

PMID- 23555383
TI  - Infected aneurysm.

PMID- 23555384
TI  - Primary aortic infections and infected aneurysms.
AB  - Primary infections of the aorta and infected aortic aneurysms are rare and are
      life threatening. Most of them are due to bacterial infection occurring in an
      atheromatous plaque or a pre existing aneurysm during bacteremia. Rarely spread
      from a contiguous septic process may be the cause. The reported hospital
      mortality ranges from 16-44%. Gram positive bacteria are still the most common
      causative organisms. More recently, Gram negative bacilli are seen increasingly
      responsible. The mortality rate is higher for the Gram negative infection since
      they most often cause supra renal aneurysms and are more prone for rupture. Best
      results are achieved by appropriate antibiotics and aggressive surgical
      treatment. Excision of the infected aneurysm sac as well as surrounding tissue
      and in situ reconstruction of aorta is the preferred treatment. Pedicled omental
      cover also helps to reduce infection. Long term antibiotic is needed to prevent
      reinfection. Mortality is high for those who undergo emergency operation, with
      advanced age and for nonsalmonella infection.

PMID- 23555385
TI  - Pathogenesis of aortic dissection: elastic fiber abnormalities and aortic medial
      weakness.

PMID- 23555386
TI  - Compression sclerotherapy for primary valvular insufficiency -from liquid to foam
      .
AB  - The history of sclerotherapy of varicose veins of lower extremities dates back to
      1840's. The use of stronger sclerosants thereafter led to serious complications,
      and the use of sclerotherapy decreased for varicose veins. However, sclerotherapy
      again became popular after introduction of safer sclerosant and compression
      sclerotherapy. After introduction of sclerosing foam in mid 1990's, many
      phlebologists are now in favor of the use of sclerosing foam instead of the use
      of sclerosing liquid. However, few studies have focused on the efficacy of
      sclerosing foam compared with that of sclerosing liquid in sclerotherapy of
      venous insufficiency. In Europe, the 1(st) and 2(nd) European Consensus Meetings
      on Foam Sclerotherapy (ECMFS) were already taken place in Germany. In this
      review, we discuss the efficacy of sclerosant foam in comparison with liquid
      form. Furthermore, solved and unsolved questions on safety aspect of foam
      sclerotherapy are also discussed.

PMID- 23555387
TI  - Comparison of Endovenous Laser Treatment for Varicose Veins with High Ligation
      Using Pulse Mode and without High Ligation Using Continuous Mode and Lower
      Energy.
AB  - PURPOSE: To compare two methods of endovenous laser treatment (EVLT) for primary
      varicose veins of lower extremities: first-EVLT combined with high ligation of
      great saphenous vein using pulse mode ablation and 12 W laser ; second-EVLT
      without high ligation and using lower energy (10 W) and continuous mode.
      MATERIALS AND METHODS: Ninety-three limbs of 75 patients were treated by 980 nm
      diode laser into the great saphenous veins from June, 2003. In the first group of
      45 patients, (HL group), we performed a division of the sapheno-femoral junction
      after high ligation and EVLT was done with a 12 W laser in a pulse mode. In the
      second group of 30 patients (NL group) EVLT was performed without high ligation
      with a 10 W laser in a continuous mode using a laser fiber drawing device.
      RESULTS: Operation time was significantly shorter in the NL group compared to the
      HL group (p < 0.05), and the early occlusion rates were 100% (HL group) and 97%
      (NL group). Subcutaneous bleeding occurred in 9 limbs (16%) in the HL group and 2
      limbs (6%) in the NL group. In the NL group there was one case complicated with
      thrombus which extended into the femoral vein. CONCLUSION: High ligation at
      sapheno-femoral junction is not necessary for EVLT and a lower energy continuous
      mode laser induces a lower rate of complications compared with a pulse mode
      ablation at a higher energy level. However, close follow-up with duplex scanning
      is necessary in early postoperative period.

PMID- 23555388
TI  - Plaque Tissue Components Obtained from De Novo Lesions may Predict Restenosis
      after Directional Coronary Atherectomy.
AB  - BACKGROUND: A part of coronary stenotic lesions treated with directional coronary
      atherectomy (DCA) occur restenosis several months later. Specimens obtained by
      first DCA, present the histology of culplit lesions and may predict restenosis
      after PCI. METHODS: The study group comprised 76 patients (male/female 65/11, age
      61 +/- 11 years). Restenosis, defined as > 50% stenosis diameter by quantitative
      cineangiography, was present in 26 patients. The other 50 patients (< 50%
      stenosis) constitute the "no restenosis" group. Inflammatory cells and other
      atheroma components were planimetrically quantified as a percentage of total
      tissue area. RESULTS: As regards lymphocytes, neutrophils and smooth muscle
      cells, the grade of amount of cells did not differ between restenosis group and
      no restenosis group. The amount of obtained arterial media was similar, too.
      However, the area occupied by macrophages or calcified fragments was
      significantly larger in restenosis group than no restenosis group. And there was
      a tendency toward larger area occupied by cholesterol gruel, thrombus and
      myxomatous extracellular matrix (ECM) in restenosis group. CONCLUSION: Rich
      macrophages infiltration, calcified fragments, cholesterol rich gruel and
      myxomatous ECM from primary lesions can be predictors of restenosis after DCA,
      suggesting a possible role in restenotic process after PCI.

PMID- 23555389
TI  - Long-term Results of Reconstructive Surgery for the Unilateral Aortoiliac
      Occlusive Disease and Future Risks of Contralateral Iliac Events.
AB  - OBJECTIVE: Our experience with unilateral iliac reconstructive surgery was
      retrospectively reviewed, and the long-term patency and the morphological
      information was disclosed. In addition, the prognosis of contralateral iliac
      artery was examined, because future contralateral iliac events seem to be
      important for durability of unilateral iliac revascularizations. MATERIALS AND
      METHODS: 148 patients (mean age, 66.9 years; 88% male) who had undergone
      unilateral aortoiliac reconstruction without contralateral iliac lesions were
      evaluated. The unilateral aortoiliac reconstructive procedures included 112 (76%)
      aorto or iliofemoral bypasses, 27 (18%) femorofemoral bypasses, and 9 (6%)
      axillofemoral bypasses. The indications for arterial reconstruction were
      disabling claudication and limb salvage in 125 (84%) and 23 (16%) patients,
      respectively. Preoperative arteriograms were reviewed to determine the Inter
      Society Consensus (TASC II) classification categorizing iliac artery lesions.
      Contralateral iliac events were defined as any arterial reconstructive procedure,
      intervention, amputation for progression of contralateral iliac disease, or
      repair of abdominal aortic aneurysm (AAA). The Kaplan-Meier survival analysis was
      used to predict long-term results in patients grouped based on various factors
      which were compared using univariate and multivariate analyses. RESULTS: In the
      148 patients, unilateral iliac reconstructive procedures were undertaken in 83
      (56%) patients with TASC II type D lesions, 34 (23%) patients with TASC II type C
      lesions, and 31 (21%) patients with TASC II type B lesions. Overall primary and
      secondary patency rates were 93.8% and 96.5% at 3 years and 90.0% and 93.9% at 5
      years. A multivariate analysis disclosed critical limb ischemia influencing
      primary patency rates, and type of aortoiliac reconstruction or gender
      influencing secondary patency rates. TASC II classification did not affect
      primary or secondary patency rates. During the follow-up period, 15 contralateral
      iliac events occurred, including 11 aortoiliac reconstructive or interventional
      procedures, 3 repairs of AAA, and one case of bilateral thigh amputation due to
      acute aortic occlusion. The overall probability of contralateral iliac events was
      2.2% at 3 years and 5.9% at 5 years. CONCLUSION: The long-term patency following
      unilateral iliac reconstructive surgery was satisfactory, and not affected by
      morphology of the iliac artery. Also, the future risk of contralateral iliac
      events appeared to be low.

PMID- 23555390
TI  - A case of acute arterial thrombosis caused by nephrotic syndrome.
AB  - Venous thromboembolic complications are frequently caused by nephrotic syndrome,
      while arterial thrombosis has rarely been reported. We report the successful
      treatment of a 53-year-old man who suffered from sudden severe pain of the left
      lower limb and facial edema. Abdominal computed tomography showed that the left
      common iliac artery was occluded from its origin. Although he had left peroneal
      nerve paralysis, thrombectomy and fasciotomy were performed for limb salvage.
      Renal biopsy revealed minimal change nephrotic syndrome after the operation. No
      recurrence has been observed. Nephrotic syndrome might be considered as a cause
      of acute arterial thrombosis.

PMID- 23555391
TI  - A case of persistent sciatic artery aneurysm accompanied by a persistent sciatic
      vein.
AB  - A persistent sciatic artery is a rare anomaly. On the other hand, a persistent
      sciatic vein is frequently associated with Klippel-Trenaunay syndrome. In a 71
      year-old female with a complete-type persistent sciatic artery aneurysm, we
      performed aneurysmectomy and right femoropopliteal bypass surgery. The right
      popliteal vein drained into the femoral vein via a lower-type persistent sciatic
      vein and the deep femoral vein. The superficial femoral artery and vein were
      hypoplastic. Since only 4 cases of a coexisting persistent sciatic artery and
      vein have been reported, we report this extremely rare case.

PMID- 23555392
TI  - Common iliac aneurysm rupture after previous aortic aneurysm resection.
AB  - INTRODUCTION: Ruptured common iliac aneurysms present with diagnostic and
      therapeutic challenges. This case describes the successful outcome in a patient
      with complex vascular surgical history. CASE PRESENTATION: An elderly patient
      presented with abdominal pain confirmed by CT as leaking iliac aneurysm. He had
      previously undergone an aorto-bifemoral bypass graft for ruptured abdominal
      aortic aneurysm. The iliac aneurysm was treated by simple ligation of the
      external iliac artery. DISCUSSION: Aorto-bifemoral bypass graft may be required
      for aortic aneurysm repair in severe iliac calicification. Iliac artery fed by
      retrograde blood flow from the aorto-bifemoral bypass graft contributed to
      aneurysm development here.

PMID- 23555393
TI  - Acute palmer digital artery occlusion treated using endoscopic ablation of the
      thoracic sympathetic.
AB  - Acute occlusion of the digital arteries frequently causes painful infarction
      requiring digital amputation. We describe a 55-year-old male patient who
      presented with acute onset of digital ischemia with impending gangrene on the
      right hand. Because angiography revealed bypass surgery was not feasible, he
      underwent thoracoscopic sympathectomy (TS) one week after onset of the symptom,
      which resulted in rapid pain resolution. He was diagnosed, thereafter, with
      malignant rheumatoid arthritis and methotrexate was administered. Postoperative
      angiography revealed that the occluded digital artery had become recanalized.
      Timely TS is therefore a treatment of choice for acute digital ischemia.

PMID- 23555394
TI  - A case of double inflammatory aneurysms in the thoracic and abdominal aorta
      repaired simultaneously.
AB  - A 54-year-old male who had been experiencing a high fever for a month was
      admitted to a local hospital for examination. Computed tomography revealed
      saccular aneurysms in the descending thoracic aorta and infrarenal abdominal
      aorta. The walls of the aneurysms were thickened and enhanced by intravenous
      contrast which suggested the inflammatory change. He was transferred to this
      hospital and underwent graft replacement of both the descending thoracic aorta
      and the abdominal aorta simultaneously. Simultaneous surgery should be considered
      in patients presenting with multiple inflammatory aneurysms, since inflammatory
      aneurysms have a risk of demonstrating rapid enlargement.

PMID- 23555395
TI  - The Use of Enclose((r))II Anastomosis Assist Device for the Proximal Coronary
      Branch Anastomosis to Vascular Graft.
AB  - We used the Enclose((r))II anastomosis assist device (Novare Surgical Systems,
      Inc., CA, USA), which was originally developed as an ancillary device for
      proximal anastomosis in off-pump coronary artery bypass grafting (OPCAB), to
      assist anastomosis for the vascular grafts without clamping those conduits in two
      cases. In these cases, it was difficult to clump vascular graft partially,
      because vascular graft was short. So we used Enclose((r))II anastomosis assist
      device for these cases. The advantage of this method is that the Enclose((r))II
      anastomosis assist device facilitates the anastomosis of arterial side branches
      to the artificial graft (1) by eliminating the use of partial clamp on the
      artificial conduits and (2) by providing a plane surface for easy handling for
      suture.

PMID- 23555396
TI  - First Asian PAD workshop.

PMID- 23555397
TI  - Renal cysts as strongest association with abdominal aortic aneurysm in elderly.
AB  - OBJECTIVE: The aim of this study is to investigate the positive association
      between the presence of renal cysts and AAA. PATIENTS AND METHODS: A
      retrospective chart review on the clinical data of 396 consecutive patients, who
      underwent CT scans for preoperative evaluation of thoracic and cardiovascular
      surgery in Sapporo Medical University from the period of January 2007 to December
      2008, was conducted. RESULTS: When comparing patients with renal cysts (n = 164)
      to those without (n = 233), there was a statistically significant difference
      between the presence of renal cysts and male gender (p = 0.007), hypertension (p
      = 0.003), and AAA (p < 0.001) on univariate analysis. In addition, when comparing
      patients with AAA to those without, although COPD but not AAA was associated with
      renal cysts in less than 65 years old, the presence of renal cysts was the
      strongest association with AAA among patients belonging to the 65 to 74 years old
      group and over 75 years old group on multivariate analysis. CONCLUSIONS: There is
      a statistically higher incidence of renal cysts in patients with AAA compared to
      patients without AAA in the group of elder cardiovascular patients. It is likely
      that AAA and renal cysts share a common pathogenesis.

PMID- 23555398
TI  - T-type ca(2+) channel blockers increase smooth muscle progenitor cells and
      endothelial progenitor cells in bone marrow stromal cells in culture by
      suppression of cell death.
AB  - OBJECTIVE: To examine the expression patterns and roles of voltage-dependent Ca2+
      channels in bone marrow stromal cells (BMSCs). MATERIALS AND METHODS: Ca(2+)
      currents of BMSCs were measured by the whole-cell patch clamp method. The number
      and percentage of deaths of BMSCs cultured for 14 days with or without Ca(2+)
      channel blockers were evaluated using a MTT assay and an LDH assay, respectively.
      RESULTS: T-type Ca(2+) channel current was recorded in 0, 2, 10, and 4% of BMSCs
      on days 3, 10, 17, and 24 in culture, respectively. L-type Ca(2+) channel current
      was first recorded on day 24 in 6% of BMSCs. Addition of the T-type Ca(2+)
      channel blocker mibefradil but not the L-type Ca(2+) channel blocker nifedipine
      significantly increased the cell count. Immunocytochemical analysis revealed
      increases in the counts of smooth muscle progenitor cells (SMPCs) and endothelial
      progenitor cells (EPCs). Mibefradil but not nifedipine significantly decreased
      the rate of cell death. CONCLUSION: T-type Ca(2+) channel blockers increased the
      numbers of SMPCs and EPCs in cultured BMSCs, partly through suppression of cell
      death. Thus, T-type Ca(2+) channel blockers may have the potential to provide an
      increased number of both BMSC-derived SMCs and ECs of potential use in cell and
      gene therapy.

PMID- 23555399
TI  - New Surgical Drapes for Observation of the Lower Extremities during Abdominal
      Aortic Repair.
AB  - OBJECTIVE: For the early diagnosis and therapy of peripheral thromboembolism (TE)
      as a complication of abdominal aortic repair (AAR), we developed and evaluated
      the usefulness of surgical drapes that permit observation of the lower
      extremities during AAR. MATERIALS AND METHODS: Between January 2007 and June
      2009, the handling, durability, and usefulness of new surgical drapes were
      evaluated during AAR in 157 patients with abdominal aortic aneurysms and 9
      patients with peripheral arterial disease. The drapes are manufactured by Hogy
      Medical Co. Ltd. and made of a water-repellent, spun lace, non-woven fabric,
      including a transparent polyethylene film that covers the patients' legs. This
      transparent film enables inspection and palpation of the lower extremities during
      surgery for early diagnosis and therapy of peripheral TE. RESULTS: As a
      peripheral complication, 1 patient had right lower extremity TE. This was
      diagnosed immediately after anastomosis, thrombectomy was performed, and the
      remaining clinical course was uneventful. In all patients, the drapes permitted
      observation of the lower extremities , and the dorsal arteries were palpable.
      There were no problems with durability. CONCLUSIONS: New surgical drapes permit
      observation of the lower extremities during AAR for early diagnosis and treatment
      of peripheral TE.

PMID- 23555400
TI  - Trans-Serosal Leakage of Proinflammatory Mediators during Abdominal Aortic
      Aneurysm Repair: Role of Phospholipase A2 in Activating Leukocytes.
AB  - Gut barrier failure and the resultant translocation of luminal bacteria and
      bacterial products into the systemic circulation have been proposed as pathogenic
      mechanisms of multiorgan dysfunction syndrome (MODS) in open repair of abdominal
      aortic aneurysm (AAA). Our study aimed to demonstrate the direct release of gut
      derived inflammatory mediators via the trans-serosal route in humans. Fifteen
      patients who underwent elective infrarenal open repair of AAA were randomized
      into two groups. In Group I patients (n = 10), the small intestine was
      exteriorized into a bowel bag. In Group II patients (n = 5), the small intestine
      was packed within the peritoneal cavity using large gauzes. We collected the
      bowel bag fluid in Group I and the ascites fluid, squeezed out from the gauzes at
      the end of surgery, in Group II. Leukocytes were collected from patients' blood
      samples. Incubation with the bowel bag fluid and ascites fluid caused a
      significant increase in both granulocyte pseudopod formation and CD11b expression
      compared to that with control fluid (p < 0.01). The addition of phospholipase A2
      (PLA2) inhibitor quinacrine abolished leukocyte activation by the bowel bag
      fluid. Based on these results, we consider that trasns-serosal leakage of gut
      derived mediators occurred during the open repair of AAA; further, sPLA2 may be
      the most potent mediator in the activation of leukocytes among such gut-derived
      mediators in AAA surgery.

PMID- 23555401
TI  - A case of popliteal artery aneurysm associated with popliteal artery entrapment
      syndrome.
AB  - Popliteal artery entrapment (PAE) is an uncommon syndrome. Although this
      phenomenon can cause claudication in younger populations, other clinical features
      may vary. The present report describes a case of a 48-year-old woman who was
      referred for treatment of a pulsatile mass in the right popliteal fossa. Computed
      tomography scan and magnetic resonance imaging demonstrated popliteal aneurysm
      associated with PAE. Resection of abnormal musculotendinous structures,
      aneurysmectomy and subsequent revascularization were successfully performed.
      Although PAE may lead to poststenotic dilatation and aneurysm formation, huge
      aneurysm without clinical signs of ischemia in a patient with PAE is extremely
      rare.Popliteal artery entrapment (PAE) is an uncommon syndrome. Although this
      phenomenon can cause claudication in younger populations, other clinical features
      may vary. The present report describes a case of a 48-year-old woman who was
      referred for treatment of a pulsatile mass in the right popliteal fossa. Computed
      tomography scan and magnetic resonance imaging demonstrated popliteal aneurysm
      associated with PAE. Resection of abnormal musculotendinous structures,
      aneurysmectomy and subsequent revascularization were successfully performed.
      Although PAE may lead to poststenotic dilatation and aneurysm formation, huge
      aneurysm without clinical signs of ischemia in a patient with PAE is extremely
      rare.

PMID- 23555402
TI  - Surgical treatment of complications associated with the angio-seal vascular
      closure device: report of three cases.
AB  - The Angio-Seal arterial closure device consists of several bioabsorbable
      components and is used for hemostasis of arterial puncture sites. We report 3
      cases of hemorrhagic and ischemic complications related to Angio-Seal use. Two
      cases were treated successfully by surgical removal of the device. In the third
      case surgical removal of the device failed and additional intervention was
      necessary. The unique structure of the Angio-Seal and the most likely cause of
      failure should be considered when treating device-related complications.

PMID- 23555403
TI  - Disseminated intravascular coagulation with acutely-thrombosed popliteal
      aneurysm.
AB  - Disseminated intravascular coagulation (DIC) is an extremely rare complication of
      acute thrombosis in popliteal aneurysms and makes it difficult to restore the
      blood flow with thrombolytic therapy or surgical repair. A 75-year-old man with a
      history of hypertension presented to the emergency department with complaints of
      right leg pain and bleeding tendency over a 5-day period. The laboratory findings
      and multislice computed tomography were suggestive of overt DIC caused by acute
      thrombosis in the right popliteal aneurysm. Successfully treated with medication,
      he could discharge without surgical or thrombolytic recanalization of the
      aneurysm.

PMID- 23555404
TI  - Multivisceral fibromuscular dysplasia: an unusual case of renal and superior
      mesenteric involvement.
AB  - Fibromuscular dysplasia (FMD), a disease process which leads to arterial stenosis
      and aneurysm formation, has been reported to occur in almost every arterial bed
      in the body. However, multivisceral FMD is rare, and we report a 43-year-old
      woman with hypertension who had incidental finding of FMD of both renal arteries
      and the superior mesenteric artery (SMA). The left renal aneurysms and right
      renal stenosis were successfully treated by aneurysm resection and aortorenal
      bypass and percutaneous transluminal angioplasty, respectively. The asymptomatic
      FMD of the SMA was treated conservatively. The indications for intervention in
      patients with asymptomatic FMD have not been clarified till date, and we
      therefore advise a close surveillance program.

PMID- 23555405
TI  - A case of popliteal artery entrapment syndrome with chronic total occlusion.
AB  - Popliteal artery entrapment syndrome (PAES) is rare congenital anomaly that
      occurs due to compression of the popliteal artery by adjacent musculotendinous
      structures. We report a 54-year-old woman with PAES of total popliteal arterial
      occlusion was successfully treated by release of the muscle bundle and
      reconstruction of the popliteal artery. Pathologic examination revealed that the
      extracted portion of the popliteal artery had chronic total occlusion with
      fibrosis and destruction of internal elastic membrane. We should deliberate
      whether we reconstruct the popliteal artery in addition to release of the
      aberrant muscle bundle due to the preoperative examination to prevent the
      reoperation.

PMID- 23555406
TI  - A case of inferior mesenteric artery aneurysm with an occlusive disease in
      superior mesenteric artery and the celiac artery.
AB  - A 72 year-old man was referred to our hospital for treatment of a gradually
      expanding inferior mesenteric artery (IMA) aneurysm associated with an occluded
      superior mesenteric artery (SMA) and a severely stenosed celiac artery (CA).
      Using 64-slice computer tomography (CT), we were able to accurately define a
      precise collateral visceral circulation from the IMA to the SMA and the CA,
      greatly clarifying preoperative strategy. The aneurysm was subsequently removed,
      with revascularization of the SMA and the CA accomplished through grafts from the
      abdominal aorta using 6 mm polytetrafluoroethylene (PTFE) grafts.

PMID- 23555407
TI  - Kawasaki disease as a systemic vasculitis in childhood.
AB  - Kawasaki disease is a disease of unknown etiology that most frequently affects
      infants and children under 5 years of age. Inflammation occurs in medium-sized
      muscular arteries throughout the body including the coronary artery, being
      classified as a systemic vasculitis syndrome. Histopathological investigations of
      Kawasaki disease have mainly focused on the coronary artery because it is
      directly associated with the cause of death. However, to identify the cause and
      pathology of Kawasaki disease, it is necessary to investigate lesions of whole
      organs. Thus, we attempted to review lesions in organs other than the heart and
      hypotheses of pathogenesis recently attracting attention.

PMID- 23555408
TI  - IgG4-related Inflammatory Abdominal Aortic Aneurysm, Spectrum of IgG4-related
      Chronic Periaortitis.

PMID- 23555409
TI  - Diagnostic Imaging of Pulmonary Thromboembolism by Multidetector-row CT.
AB  - For diagnosis of pulmonary thromboembolism, multidetector-row computed tomography
      (CT) is a minimally invasive imaging technique that can be performed rapidly with
      high sensitivity and specificity, and has been increasingly employed as the
      imaging modality of first choice for this disease. Since deep vein thrombosis in
      the legs, which is important as a thrombus source, can be evaluated immediately
      after the diagnosis of pulmonary thromboembolism, this diagnostic method is
      considered to provide important information when deciding on a comprehensive
      therapeutic strategy for this disease.

PMID- 23555410
TI  - MRI and MRA of Aortic Disease.
AB  - Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) play a
      critical role in diagnosing aortic disease such as aortic dissection and
      aneurysm. Additionally, the advent of contrast-enhanced MRA has allowed MRA to
      advance markedly and several new imaging techniques to emerge as well. While
      computed tomography (CT) angiography using multidetector-row CT is a significant
      innovation, MRA may generate more useful diagnostic information, such as on the
      artery of Adamkiewicz.

PMID- 23555411
TI  - Multidetector-row CT Angiography of Lower Extremities: Usefulness in the
      Diagnosis of and Intervention for Peripheral Arterial Disease.
AB  - CT angiography (CTA) based on the data acquired by multidetector-row CT (MDCT) is
      an established, minimally invasive modality for imaging peripheral arteries. CTA
      has been used to assess peripheral arterial disease before treatment, and it has
      replaced conventional angiography for the diagnostic evaluation of peripheral
      arteries. MDCT can optimize both the long scan length and spatial resolution. CTA
      using MDCT depicts the fine structures of vessels. Recently, automated CTA
      analysis software has been developed for measurement of the vascular lumen. The
      software can automatically measure the diameters of short axial sections at the
      post-processing workstation. Measurement of the vascular lumen is useful in the
      planning of intravascular treatment for peripheral arterial disease. CTA is also
      utilized in assessing the intravascular lumen after metallic stent placement.

PMID- 23555412
TI  - Mortality from pulmonary heart disease in Japan, 1979-2006.
AB  - OBJECTIVE: In Japan, there have been no reports on the time-trends of mortality
      rates from pulmonary heart disease without pulmonary embolism (PHD). Our aim was
      to examine the annual changes of mortality in Japan. MATERIALS AND METHODS:
      Annual age-adjusted and age-specific PHD mortality for Japanese residents during
      1979-2006 were calculated from "Vital statistics of Japan" and census data and
      population estimates for intercensal years. RESULTS: The number of age-adjusted
      deaths from PHD continued to decrease throughout the study period. The age
      specific mortality from PHD increased throughout the life span except below 1
      year old and decreased in recent years. Male mortality was greater at most ages.
      In Poisson regression analysis, the relative risk of death from PHD was increased
      in males and the aged except below 1 year-age, and decreased in recent years. The
      annual number of deaths from idiopathic pulmonary arterial hypertension/heritable
      pulmonary arterial hypertension (IPAH/HPAH) continued to increase throughout the
      study period. The number of annual new cases with IPAH/HPAH was estimated to be
      about 400 in a recent period of 10 years. CONCLUSION: The annual number of deaths
      from PHD decreased, and those from IPAH/HPAH increased significantly during 1979
      2006 in Japan.

PMID- 23555413
TI  - Recent outcomes of surgery for chronic type B aortic dissection.
AB  - OBJECTIVE: Chronic type B dissection though optimal is still considered to be a
      controversial procedure, even in the advent of stent grafts. Recently, we used a
      novel surgical technique involving left axillary perfusion to analyze the results
      of our surgical strategy and compare them with those reported in the literature.
      MATERIALS AND METHODS: Between August 2004 and July 2009, 39 patients underwent
      graft replacement for chronic type B aortic dissection. The left axillary artery
      was used for perfusion inflow. Perfusion was maintained at approximately 23C
      during open proximal anastomosis. The graft was anastomosed to the distal true
      lumen whenever possible. RESULTS: Open proximal anastomosis was performed in 22
      patients (56%). In 24 cases (62%), grafts were anastomosed to the true lumen of
      the peripheral aorta. The early overall mortality rate was 3% (1 patient).
      Permanent cerebral infarction occurred in 2 patients (5%); and paraparesis, in 1
      patient (3%). The Kaplan-Meier survival estimates were 91% at 2 years and 88% at
      5 years. CONCLUSION: Our surgical strategy is associated with excellent short
      term and midterm outcomes. Although further investigation is needed, this
      strategy may be useful for patients with chronic type B dissection.

PMID- 23555414
TI  - Routine diagnostic venous ultrasound and las for leg edema of unknown cause.
AB  - OBJECTIVE: To verify the diagnostic efficiency of venous duplex ultrasound and
      lymphangioscintigraphy (LAS) in establishing the cause of leg edema and to
      clarify the pathology of these leg edemas. MATERIALS AND METHODS: Between April
      2009, and March 2010, 62 patients with leg edema of unknown origin were referred
      to the Edema Clinic of the Yamaguchi University Graduate School of Medicine. All
      patients underwent a venous duplex ultrasound scan and LAS. RESULTS: Of 62
      patients, lymphatic insufficiency, venous insufficiency or both was diagnosed in
      42 (68%), and lymphedema, in 29 (47%). Venous duplex ultrasound detected obvious
      venous disorders in only 13 (21%), and for 20 patients, the ultrasound and LAS
      did not reveal any abnormalities; however, for 15 of the 20 (24% of all
      patients), venous edema was attributed to functional causes. CONCLUSION: Venous
      duplex ultrasound and LAS assisted in the diagnosis of leg edema of unknown
      origin and also proved useful in establishing treatment strategies.

PMID- 23555415
TI  - A fenestrated stent graft for endovascular repair of an ascending aortic
      pseudoaneurysm.
AB  - Endovascular stent grafting is a novel therapeutic technique for repairing aortic
      aneurysms, and is especially useful for descending aortic aneurysm and aneurysm
      at the distal arch. However, no effective endovascular approach for the ascending
      aorta has been reported a remaining site for endovascular repair because of the
      anatomical restrictions and the presence of vital branches to the head and arms
      that are present in this region. This report describes an endovascular stent
      graft repair of a pseudoaneurysm at the ascending aorta using a fenestrated stent
      graft. The fenestrated stent graft is easy to use and less invasive for the
      endovascular repair of the ascending aorta.

PMID- 23555416
TI  - Rare complication after stripping operation: a case report of mycobacterium
      abscessus infection.
AB  - Mycobacterium abscessus is an acid-fast nontuberculous mycobacterium that grows
      rapidly in culture. The organism is found in dust, soil, and water and after
      trauma, it may infect skin and soft tissue. The organism is rarely found in
      humans, and infections occurring after cardiovascular surgery are rare clinical
      events. To our knowledge, only a few cases of hemodialysis arteriovenous graft
      infection and endocarditis caused by M. abscessus have been described. We
      reported a first case of patient with M. abscessus graft infection after a
      stripping operation and skin grafting to a left lower leg ulcer.

PMID- 23555417
TI  - A case of inflammatory solitary internal iliac artery aneurysm successfully
      treated by an endovascular procedure.
AB  - An inflammatory aneurysm localized in the iliac artery is very rare. Aneurysms of
      the common iliac artery have been reported sporadically, but there has been no
      report of internal iliac artery aneurysm. The patient was a 64-year-old male
      presenting with left lower abdominal pain and fever. Abdominal computed
      tomography (CT) revealed an aneurysm of 42 * 52 mm in the left internal iliac
      artery. The aneurysmal wall had thickened and mantle sign was positive. Since the
      aneurysm was expected to adhere tightly to surrounding tissues, the risk of open
      surgery was judged to be high, and coil embolization of the aneurysm and the
      peripheral branches of the internal iliac artery was performed. Postoperatively,
      the left lower abdominal pain disappeared, and signs of inflammation were
      mitigated. The endovascular procedure was extremely effective for the treatment
      of this inflammatory iliac artery aneurysm.

PMID- 23555418
TI  - Chronic occlusion of an abdominal aortic aneurysm.
AB  - A 67-year-old woman with peripheral arterial occlusive disease in both lower
      extremities, secondary to an abdominal aortic aneurysm, developed chronic total
      occlusion of the abdominal aortic aneurysm during the 3-year follow-up period.
      She suffered from sudden onset of paraplegia 3 months after palliative
      axillobifemoral bypass grafting and died of pneumonia. The paraplegia was
      considered to have been caused by thrombosis of lumbar arteries that might have
      served as an important collateral pathway in the distal spinal cord, due to
      proximally propagated infrarenal aortic thrombosis. It is necessary to recognize
      that chronically thrombosed abdominal aortic aneurysm (AAA) still has a risk of
      causing serious complications with a high mortality rate, especially in cases
      treated medically or with palliative operations.

PMID- 23555419
TI  - Mondor's Disease in the Arm after Intravenous Chemotherapy Following Breast
      Cancer Surgery.
AB  - We present a case of superficial thrombophlebitis of the arm, known as a variant
      of Mondor's disease. A 71-year-old woman who underwent a left simple mastectomy
      with axillary dissection for breast cancer had a cord-like vein structure in the
      right antecubital fossa following postoperative intravenous chemotherapy, and
      complained of limited elbow extension due to the firm and inflexible structure.
      She successfully underwent surgical resection of the vein cord to relieve the
      elbow motion limitation.

PMID- 23555420
TI  - Elastic stocking-induced foot necrosis in a patient with severe pneumonia.
AB  - Elastic stockings (ES) are widely used for the prevention of venous
      thromboembolism. Here we report a case of foot ulcers induced by ES in patients
      with pneumonia and hypoxia. A 94-year-old woman was admitted for the treatment of
      pneumonia. The patient had been wearing an ES because of a history of deep vein
      thrombosis of the leg. Multiple foot ulcers occurred within 24 hours after the
      admission despite the absence of peripheral arterial occlusive disease. The
      ulcers took almost 5 months to heal. For patients with hypoxia, ES may further
      deteriorate local tissue hypoxia and thus should be used carefully.

PMID- 23555421
TI  - Progress and Current State of Coronary CT.
AB  - The recent appearance of multislice computed tomography (CT) has enabled
      noninvasive imaging of the coronary artery. Particularly, the appearance of 64
      row CT has rapidly promoted its spread into routine medical practice. In this
      report, progress and current state of coronary CT employing multislice CT are
      outlined.

PMID- 23555422
TI  - Prophylactic Implantation of Inferior Vena Cava Filter during Endovascular
      Therapies for Deep Venous Thrombosis of the Lower Extremities.
AB  - Patients with deep venous thrombosis (DVT) of the lower extremities have an
      increased risk of pulmonary emboli and post-thrombotic syndrome. Traditionally,
      they are treated medicinally, with anticoagulation therapy. Currently,
      endovascular therapies, with their higher efficiency, have replaced previously
      attempted systemic fibrinolytic therapies. There is a continuing controversy in
      the temporary use of filters in the inferior vena cava during these endovascular
      therapies, which may include catheter-directed thrombolysis, manual aspiration,
      mechanical thrombectomy, percutaneous transluminal angioplasty and placement of
      self-expandable metallic stents. Here, we present an overview of the literature
      and analysis on the application of prophylactic implantation of an inferior vena
      cava filter during endovascular therapy for DVT of the lower extremities.

PMID- 23555423
TI  - Prediction of limb salvage after therapeutic angiogenesis by autologous bone
      marrow cell implantation in patients with critical limb ischemia.
AB  - PURPOSE: Despite advances in therapeutic angiogenesis by bone marrow cell
      implantation (BMCI), limb amputation remains a major unfavorable outcome in
      patients with critical limb ischemia (CLI). We sought to identify predictor(s) of
      limb salvage in CLI patients who received BMCI. MATERIALS AND METHODS: Nineteen
      patients with CLI who treated by BMCI were divided into two groups; four patients
      with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the
      remaining 15 patients without (salvage group). We performed several blood-flow
      examinations before BMCI. Ankle-brachial index (ABI) was measured with the
      standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum
      of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen
      inhalation. (99m)technetium-tetrofosmin ((99m)Tc-TF) perfusion index was
      determined at the foot and lower leg as the ratio of brain. RESULTS: Maximum
      TcPO2 (p = 0.031) and (99m)Tc-TF perfusion index in the foot (p = 0.0068) was
      significantly higher in the salvage group than in the amputation group. Receiver
      operating characteristic (ROC) curve analysis identified maximum TcPO2 and
      (99m)Tc-TF perfusion index in the foot as having high predictive accuracy for
      limb salvage. CONCLUSION: Maximum TcPO2 and (99m)Tc-TF perfusion index in the
      foot are promising predictors of limb salvage after BMCI in CLI.

PMID- 23555424
TI  - Ten years experience of aortic root replacement using a modified bentall
      procedure with a carrel patch and inclusion technique.
AB  - OBJECTIVE: A modified Bentall procedure with a Carrel patch and inclusion
      technique (Modified Bentall Procedure) has been used to treat combined disease of
      the aortic valve and aortic root. The current study examined the outcomes of this
      surgical technique. MATERIALS AND METHODS: Between April 1999 and March 2009, 16
      patients (10 males, 6 females; 63.3 +/- 9.4 years) underwent elective surgery
      involving the Modified Bentall Procedure and no additional surgery, so they were
      included in the study. RESULTS: The mean cardiopulmonary bypass time was 140.2 +/
      34.4 min (range: 97-232 min), and aortic cross-clamp time was 97.3 +/- 16.6 min
      (range: 76-132 min). There were no hospital deaths. No patients required
      additional surgery to correct excessive bleeding. The follow-up rate was 100%
      (16/16). The mean follow-up period was 5.6 +/- 2.8 years (range: 0.7-9.9 years).
      One of the 16 patients died (6.3%) due to lung cancer, and 1 of the 15 surviving
      patients required additional surgery (6.7%) for a thoracic aortic aneurysm.
      Kaplan-Meier analysis found that 1-year and 5-year survival and event-free
      survival rates were all 100%. CONCLUSIONS: The Modified Bentall Procedure
      provided satisfactory results over both the short term and long term.

PMID- 23555425
TI  - Severe limb ischemia related to previous abdominal aortic aneurysm repair induced
      by acute aortic dissection.
AB  - We described the first case of limb ischemia induced by acute aortic dissection
      in the patient with previous abdominal aortic aneurysm (AAA) repair. A 56-year
      old male was referred for severe limb ischemia. He underwent AAA repair one month
      before the referral. Computed tomography (CT) scan revealed Stanford type B
      aortic dissection extended to the proximal anastomosis site of the AAA repair.
      The false lumen made the complete interruption of antegrade blood flow at the
      proximal anastomosis site of the AAA repair.

PMID- 23555426
TI  - Balloon-trapped Technique for Successful OptEaseFilter Retrieval.
AB  - PURPOSE: To describe a case of successful retrieval of OptEase filter, using the
      balloon-trapped technique, after failure of its retrieval by the standard
      techniques. CASE REPORT: An 82-year-old man had an inferior vena cava filter
      placed for deep venous thrombosis prophylactically. Seven days after successful
      catheter-directed thrombolysis, the filter was retrieved after changing the
      position to caudal, using a standard angioplasty balloon. The patient was
      discharged on warfarin anticoagulant. CONCLUSION: Balloon-trapped removal of the
      OptEase filter that failed standard retrieval attempt is an effective and safe
      technique that can be performed using commonly available tools and familiar to
      most interventionalists.

PMID- 23555428
TI  - Ruptured tuberculous false aneurysm of the abdominal aorta: a case report.
AB  - Tuberculous false aneurysm of the aorta is rare and has an unpredictable
      complication of aneurysm rupture. We report a case of a 32-year old woman who was
      referred to the Department of Vascular Surgery, Avicenne Hospital for severe
      abdominal pain. Chest x-ray revealed miliary tuberculosis. Contrast enhanced
      computed tomography (CT) scan showed a false aortic aneurysm involving the
      juxtarenal aorta. Antituberculous treatment was started because of high
      presumption of tuberculosis. Five days later, the patient presented with symptoms
      of aneurysm rupture. She underwent an emergency a surgical resection of the
      aneurysm with repair of the aortic wall defect by a Dacron Silver patch. The
      histopathologic examination of the aortic wall showed features of tuberculosis.

PMID- 23555427
TI  - Histopathologic Characteristics of a Coronary-pulmonary Artery Fistula with a
      Coronary Artery Aneurysm.
AB  - Here, we report a case of a 59-year-old woman with a coronary-pulmonary artery
      fistula with a concomitant coronary artery aneurysm, which comprised an anomalous
      coronary artery originating at the right coronary cusp, an aberrant branch of the
      left anterior descending artery, and a coronary artery aneurysm draining into the
      main pulmonary artery. Histopathologically, non-dilated anomalous coronary artery
      showed the preservation of internal elastic lamina and medial smooth muscle cell
      phenotype which lacked in the aneurysmal wall. Thus, the disrupted internal
      elastic lamina and phenotypic change of medial smooth muscle cells might
      contribute to aneurysm formation in a coronary-pulmonary arterial fistula.

PMID- 23555429
TI  - Usage of external shunt in hybrid approach for aortic arch aneurysm to restore
      cerebral oxygenation.
AB  - A hybrid approach, combining open and endovascular procedures, may be a less
      invasive substitute to correct aortic arch pathologies in high-risk patients. We
      describe an 82-year-old male patient with an atherosclerotic aortic arch
      aneurysm, which was treated with proximal transposition of all arch branches and
      endovascular aortic arch repair. During the left common carotid artery
      reconstruction, oxygen saturation level of the left cerebral hemisphere decreased
      lower than the safety limit. To re-establish brain perfusion, we installed an
      external shunt from the right common femoral artery to the left common carotid
      artery. The oxygen saturation was restored to an acceptably safe level, and the
      patient tolerated the procedure without any signs of postoperative ischemic
      stroke.

PMID- 23555430
TI  - A case of iatrogenic subclavian artery injury successfully treated with
      endovascular procedures.
AB  - We report a case of a life-threatening massive hemothorax caused by iatrogenic
      injury of the right subclavian artery. The patient was successfully treated with
      placement of a covered stent. During the procedure, occlusion balloon catheters
      rapidly controlled the massive bleeding.

PMID- 23555432
TI  - Successful surgical treatment of right subclavian artery aneurysm with a
      hypoplastic left vertebral artery using temporary cerebral perfusion to prevent
      cerebral ischemia.
AB  - A 71-year-old man had a right subclavian artery aneurysm (dimension, 30 * 38 mm)
      that was adjacent to the right common carotid artery and exceedingly close to the
      right vertebral artery. The patient had a marked hypoplastic left vertebral
      artery, dominant right vertebral artery, and an incompletely formed and
      underdeveloped circle of Willis in the skull. While performing a median
      sternotomy and supraclavicular incision during the operation, we used temporal
      shunting for the cerebral perfusion. The subclavian artery aneurysm was resected,
      and a 10-mm diameter woven Dacron graft was used for reconstructing the
      subclavian artery. The postoperative course was uneventful, and the patient was
      discharged from the hospital 18 days after surgery. Temporal shunting for
      maintaining cerebral perfusion was useful in preventing cerebral ischemia, and
      the median sternotomy plus supraclavicular incision approach afforded an
      unobstructed view of the surgical field.

PMID- 23555431
TI  - Mycotic abdominal aneurysm caused by campylobacter fetus: a case report for
      surgical management.
AB  - We report a rare case of mycotic abdominal aortic aneurysm associated with
      Campylobacter fetus. A 72-year-old male admitted to the hospital because of pain
      in the right lower quadrant with pyrexia. The enhanced abdominal computed
      tomography (CT) examination showed abdominal aortic aneurysm (AAA) measuring 50
      mm in maximum diameter and a high-density area of soft tissue density from the
      right lateral wall to the anterior wall of the aorta. However, since the patient
      showed no significant signs of defervescence after antibiotics administration, so
      we performed emergency surgery on the patient based on the diagnosis of impending
      rupture of mycotic AAA. The aneurysm was resected in situ reconstruction using a
      bifurcated albumin-coated knitted Dacron graft was performed. The cultures of
      blood and aneurysmal wall grew Campylobacter fetus, allowing early diagnosis and
      appropriate surgical management in this case, and the patient is making
      satisfactory progress. This is the fifth report of mycotic AAA characterizing
      culture positive for Campylobacter fetus in blood and tissue culture of the
      aortic aneurysm wall.

PMID- 23555433
TI  - A case of effective cerebrospinal fluid drainage for paraplegia caused by acute
      aortic dissection.
AB  - A 65-year-old man with sudden back pain was transferred to our hospital by
      ambulance, who also complained of sensory and motor disorder of bilateral legs on
      arrival. The neurological disorder was gradually aggravated and paraplegia below
      the level of Th10 was manifested. Computed tomography demonstrated DeBakey IIIb
      acute aortic dissection; therefore, the paraplegia was thought to be due to
      spinal cord ischemia caused by the acute aortic dissection. Emergent
      cerebrospinal fluid drainage was performed, and it was very effective for the
      relief from paraplegia. The hospital course after the drainage was uneventful and
      he was discharged on the 39th day after the onset of symptoms.

PMID- 23555434
TI  - Correlation between Changes in Leg Blood Flow and Ankle-Brachial Pressure Index:
      A Study Using Laser Doppler Flowmeter -The 1st Report-.
AB  - OBJECTIVE: The objective of this study was to use non-invasive laser Doppler
      flowmeter to measure changes in blood flow in peripheral vessels in the legs
      before and after stress induced by leg elevation stress test and investigate
      correlations with the ankle-brachial pressure index (ABI). METHODS: Subjects
      included 28 patients over 20 years of age (mean, 73 years) who reported chiefly
      of leg symptoms such as intermittent claudication, numbness, chills, or cramps
      had been examined at the study institution, and agreed to participate in the
      study. The ABI of both legs was measured, and patients were divided into two
      groups: low ABI (ABI <=0.9) and normal ABI (ABI >=0.9). Blood flow in the big toe
      was measured using a box-type laser Doppler flowmeter before, during, and after
      leg-elevation stress. Amplitude of the recorded waveform and changes in blood
      flow were compared. RESULTS: Average ABI was 1.09 +/- 0.10 in the normal ABI
      group (33 legs) and 0.68 +/- 0.17 in the low ABI group (21 legs). Amplitude
      before and during stress was significantly smaller in the low ABI group than in
      the normal ABI group (p <0.01), and there was a significant correlation with ABI
      before and during stresses (r = 0.4606, r = 0.5048, respectively; p <0.05).
      Change in blood flow during stress was significantly lower in the low ABI group
      than in the normal ABI group (p <0.05). There was a significant correlation
      between change in blood flow during stress and ABI in both groups (r = 0.5073; p
      <0.05). There was also a significant correlation between change in blood flow and
      change in amplitude in both groups (r = 0.5477; p <0.05). CONCLUSION: RESULTS of
      this study show, that comparing amplitude and change in blood flow before and
      after leg extension and elevation stress, there was a correlation between change
      in blood flow and amplitude, and ABI during stress. A box-type laser Doppler
      flowmeter may provide a means of screening for peripheral arterial disease.

PMID- 23555435
TI  - Outcomes of endovascular intervention for salvage of failing hemodialysis access.
AB  - OBJECTIVE: To investigate the effectiveness of endovascular balloon angioplasty
      to preserve the patency of failing hemodialysis arteriovenous fistulas (AVF) and
      prosthetic arteriovenous grafts (AVG). METHODS: Patients on hemodialysis who
      received endovascular intervention for access problems were retrospectively
      analyzed. Fistulography was performed on patients who were suspected to have
      access stenosis and balloon angioplasty performed in the same setting if a
      stenosis of >=50% is detected. Patients were followed up for post-operative
      complications and access restenosis or failure. RESULTS: 42 hemodialysis patients
      with 44 access sites (29 AVFs, 15 AVGs) required endovascular balloon
      angioplasty. There were no perioperative complications. Technical success rate
      was 100%. Median time from initial access creation to first balloon angioplasty
      was 13 months (2-146 months) for AVFs and 8 months (2-71 months) for AVGs. 19 of
      44 patients subsequently developed restenosis. Median time for restenosis or
      access failure was 11 months (1-18 months) for AVFs and 5 months (1-10 months)
      for AVGs. Kaplan-Meier analysis for access patency after endovascular
      intervention showed 72% patency at 6 months and 32% at 12 months. CONCLUSIONS:
      Endovascular balloon angioplasty is effective in restoring patency of failing
      hemodialysis accesses. Recurrence is common, and repeat interventions are
      required.

PMID- 23555436
TI  - Improve morbidity and mortality in coronary artery bypass graft surgery for
      severe atherosclerosis.
AB  - OBJECTIVES: Atherosclerosis has been identified as a risk factor for both
      morbidity and mortality in patients undergoing coronary artery bypass grafting
      (CABG). To investigate outcomes following CABG for severe atherosclerosis, and to
      determine whether different surgical techniques can reduce the risk of neurologic
      events in these patients. METHODS: We studied 225 consecutive patients who
      underwent elective isolated CABG. Routine preoperative and intraoperative
      examinations identified patients with severe atherosclerosis. We compared the
      outcomes between patients with (group A; 42 ceses) and those without (group N;
      183 cases) severe atherosclerosis. RESULTS: 36 patients (85.7%) in group A and
      176 (96.2%) in group N underwent off-pump coronary artery bypass (OPCAB); 6
      (14.3%) in group A and 7 (3.8%) in group N underwent on-pump beating CABG. Three
      patients in group A suffered deep sternal infection (7.1%), and one suffered
      stroke (2.4%) compared with none in group N. No cerebral infarction or neurologic
      events occurred in patients who underwent OPCAB (n = 212, 94.2%). CONCLUSIONS:
      Prevalence of complications was significantly greater among patients with severe
      atherosclerotic disease who underwent OPCAB than in those without atherosclerotic
      disease. Careful selection of surgical strategies can prevent perioperative
      stroke and reduce mortality.

PMID- 23555437
TI  - Platelet nitric oxide signaling system in patients with coronary artery disease.
AB  - BACKGROUND: Coronary artery disease (CAD) is the leading cause of death
      worldwide, and the major cause of hospital admissions in the Western countries.
      The pathogenesis of CAD is closely related to nitric oxide release and formation.
      The purpose of this study was to investigate the status of platelets nitric oxide
      in patients with coronary artery disease. METHODS: We measured platelets
      aggregation, cGMP, NO (nitrite/nitrate level), NO synthase activity, plasma NO,
      and ionized Ca(2+) in 40 healthy volunteers and 120 patients with myocardial
      infarction, unstable and stable angina, with 40 subjects in each group. The
      subjects' age mean range was from 40-51 years. RESULTS: Platelets aggregation,
      NO, cGMP, NO synthase activity, plasma NO and ionized Ca(2+) have increased
      significantly (P <0.001) across the patients groups compared to controls.
      Platelets NO synthase activity (mean +/- SD / U / 10(9) platelets) in healthy
      controls, MI, unstable angina and stable angina patients were 1.19 +/- 0.56, 1.21
      +/- 0.64, 1.64 +/- 0.98 and 1.57 +/- 0.81 respectively. The cGMP (mean +/- SD /
      pmole / 10(9) platelets) levels were 0.95 +/- 0.41, 1.53 +/- 0.64, 3.18 +/- 0.77,
      and 5.12 +/- 1.5 respectively. CONCLUSIONS: The present study demonstrated that
      platelets aggregation, NO, cGMP, NO synthase activity, plasma NO, and ionized
      Ca(2+) profoundly increased in CAD. The increases in NO-cGMP components may have
      resulted as a compensatory response to ameliorate platelet activity and Ca(2+)
      levels in CAD patients.

PMID- 23555438
TI  - Ultrasonographic character of carotid plaque and postprocedural brain embolisms
      in carotid artery stenting and carotid endarterectomy.
AB  - OBJECTIVE: To investigate ultrasonographic character of carotid plaques, and
      incidences of brain embolism in carotid angioplasty and stenting (CAS) and
      carotid endarterectomy (CEA). MATERIALS AND METHODS: CEA (22/25 symptomatic
      lesions) and CAS (17/20 symptomatic lesions) between 2007 and 2010. Embolic
      protection devices (15 occlusion and 5 filtering devices) were used during CAS.
      Carotid plaques were classified into three categories (I: calcificated, II:
      intermediately echogenic, III: echolucent). Magnetic resonance imaging (MRI) was
      used to investigate brain emboli. RESULTS: Ultrasonographic character of the
      plaques in CEA cases (I: 4%, II: 88%, III: 8%) was different from the one in CAS
      cases (I: 10%, II: 90%, III: 0%). The incidence of brain embolism in the CAS
      cases was 52.6% while 0% in the CEA cases (p = 0.00037). CAS had high incidences
      of brain embolism in any plaques (I: 100%, II: 43.8%). In the most recent 9
      procedures of CAS using occlusion devices, averaged number of embolic lesion was
      1.0 (0 post operative day; 0 POD). The number increased as 1.4 (1 POD) and 2.0 (7
      POD). CONCLUSION: CEA should be currently the first choice for most patients with
      a high-grade and symptomatic carotid artery stenosis.

PMID- 23555439
TI  - CHADS2 Score is a Poor Predictor of Non-cerebral Acute Arterial Occlusion in
      Patients with Non-valvular Atrial Fibrillation.
AB  - OBJECTIVE: The CHADS2 score is a stroke risk stratification scheme in patients
      with non-valvular atrial fibrillation (NVAF). The aim of this study was to
      determine whether the CHADS2 score can help to predict the risk of non-cerebral
      acute arterial embolism. MATERIALS AND METHODS: One hundred and seventeen
      patients who underwent surgery for non-cerebral acute arterial embolism with NVAF
      between 1997 and 2009 were enrolled in the cross sectional study. The CHADS2
      score of each patient was calculated at the onset of symptoms. The distribution
      of the CHADS2 score was compared with that of other studies analyzing patients
      with stroke. RESULTS: The perioperative mortality was 11.1%. A comparison of
      patients with stroke revealed that our distribution curves were significantly
      shifted to the left, showing that the CHADS2 score did better in predicting
      stroke than non-cerebral embolism. On the other hand, the distribution in our
      series coincides with that of NVAF patients in general. These results indicated
      that the risk of non-cerebral embolism occurs at the same rate regardless of the
      CHADS2 score. CONCLUSIONS: The CHADS2 scoring system seems to be an unreliable
      predictor of non-cerebral embolism, and may not contribute in avoiding
      potentially life-threatening acute arterial occlusion of the peripheral artery.

PMID- 23555440
TI  - Preoperative HDL-C Predicts Later Cardiovascular Events after Abdominal Aortic
      Aneurysm Surgery.
AB  - PURPOSE: To determine the predictive value of serum lipid levels on the
      development of later cardiovascular events after abdominal aortic aneurysm (AAA)
      surgery. METHODS: A total of 101 patients under 70 undergoing an elective AAA
      surgery were divided into the following two groups: 1) those who developed later
      cardiovascular events after AAA surgery, including cerebral infarction (n = 4),
      catheter intervention (PCI) or surgery for coronary artery disease (CAD) (n = 9)
      and other vascular disease. (CVE group; n = 19); 2) those without later events
      (NoCVE group: n = 82). Preoperative atherosclerotic risk factors including serum
      lipid levels were subjected to univariate and multivariate analysis. RESULTS: The
      CVE group showed a significantly lower high-density lipoprotein cholesterol (HDL
      C) level (32.9 +/- 6.6 vs 41.6 +/- 12.1 mg/dL; p <0.001), higher low-density
      lipoprotein cholesterol (LDL-C) / HDL-C ratio (4.30 +/- 1.01 vs 3.24 +/- 1.15; p
      = 0.001), and higher prevalence of mild CAD (without an indication of PCI) (p =
      0.029) preoperatively. Cox hazard analysis indicated that preexistent mild CAD
      (hazard ratio 4.70) and preoperative HDL-C <35 mg/dL (hazard ratio 3.07) were
      significant predictors for later cardiovascular events after AAA surgery.
      CONCLUSION: Patients at high risk for later cardiovascular events should require
      a careful follow-up and may also require an aggressive lipid-modifying therapy.

PMID- 23555441
TI  - Fatal Pulmonary Thromboembolism due to Inferior Vena Cava Thrombosis.
AB  - Pulmonary embolism (PE) is one of the most undiagnosed causes of death, and more
      than half of fatal PE is discovered only during autopsy. The author reports a
      case of sudden death from massive pulmonary thromboembolism due to an inferior
      vena cava (IVC) thrombosis caused by chronic pancreatitis. An extensive search
      for the location of the thrombus identified the source of emboli. The probable
      mechanism of IVC thrombosis caused by chronic pancreatitis is discussed.
      Awareness of this serious complication of chronic pancreatitis may have prevented
      the sudden death.

PMID- 23555442
TI  - Delayed postoperative paraplegia and graft infection after a thoracoabdominal
      dissection.
AB  - WE REPORT THE SUCCESSFUL TREATMENT OF THORACOABDOMINAL DISSECTION, WHICH EXTENDED
      INTO THE LEFT ILIAC ARTERY, DESPITE TWO INDEPENDENT COMPLICATIONS: graft
      infection and a relatively rare, delayed postoperative paraplegia. The paraplegia
      suddenly occurred on postoperative day 10, and after an intravenous infusion of
      heparin and methylprednisolone, it gradually subsided. Moreover, graft infection
      was diagnosed on postoperative day 27, and with continuous irrigation of
      antibiotic treatment it was cured without recurrence of infection. Although
      anticoagulation therapy is not indicated for paraplegia, we suppose that it might
      be used as an adjunct therapeutic.

PMID- 23555443
TI  - Retrievable Inferior Vena Cava Filter and Catheter Directed Thrombolysis (CDT)
      for Treating a 19-year-old Man with Acute Myeloid Leukemia Complicated by Deep
      Vein Thrombosis (DVT): A Case Report.
AB  - Here, we report a case of a 19-year-old man with acute myeloid leukemia
      complicated by deep vein thrombosis (DVT) in which we placed a retrievable
      inferior vena cava (IVC) filter during catheter directed thrombolysis (CDT). We
      were able to retrieve the IVC filter after a successful CDT and concluded that
      the use of this filter might be efficacious and better than an indwelling IVC
      filter that is associated with long-term risks. A retrievable filter and CDT
      should be considered in patients who are at transient risk for phlebemphraxis and
      require placement of a filter.

PMID- 23555444
TI  - Sequential dilatation of the superior gluteal artery following coil embolization
      of the internal iliac artery and endovascular abdominal aneurysm repair: a case
      report.
AB  - We present a case of an 80-year-old male who had a right buttock claudication
      after embolization of the right internal iliac artery and endovascular aneurysm
      repair (EVAR) for aneurysms of the right common iliac and abdominal arteries. We
      used follow-up dynamic computed tomography to measure the diameter of the
      superior gluteal artery (SGA). The comparison ratio (SGA diameter after EVAR /
      SGA diameter before EVAR) of the right SGA at 1, 3, and 9 months was 0.74, 0.80,
      and 1.1, respectively, while that of the left SGA at 9 months was 0.97. The
      patient reported using a walking stick at 1- and 3-month follow-ups but not at
      the 9-month follow-up. The computed tomography (CT) showed sequential dilatation
      of the SGA, which appeared to be associated with the relief of the buttock
      claudication.

PMID- 23555445
TI  - Iatrogenic arteriovenous fistula as a cause for leg ulcers: a case report.
AB  - An 80-year-old man presented with painful leg ulceration due to steal phenomenon
      from a groin arteriovenous fistula (AVF) 10 years following a coronary angiogram.
      The diagnosis of the AVF was confirmed by duplex examination of the groin vessels
      which demonstrated characteristic flow pattern in the femoral arterial and venous
      system. Angiography further confirmed the site of the fistulous communication and
      this was managed by a covered stent graft. We discuss the incidence of AVF, risk
      factors for its development, relevant diagnostic investigations and management
      options along with strategies to reduce the incidence of AVF following
      percutaneous punctures.

PMID- 23555446
TI  - Fibromuscular dysplasia of the lower extremities.
AB  - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, non-inflammatory vascular
      disease that mainly affects the renal and internal carotid arteries. Involvement
      of other sites, including arteries of the extremities, is uncommon, and only a
      few histologically confirmed cases have been reported. FMD of the arteries of the
      extremities can result in ischemia requiring surgical or endovascular
      reconstruction. In the present report, two cases of FMD are described: one case
      of femoropopliteal artery occlusive disease, and one case of nonsymptomatic
      progression of external iliac artery dissection, both with histological
      confirmation of FMD. Clinical presentation, treatment, outcome and histological
      findings of previously reported cases are reviewed. FMD should be considered as a
      cause of occlusion, stenosis, dissection or aneurysm of the peripheral arteries:
      although rare, it can lead to limb-threatening ischemia or life-threatening
      aneurysm rupture.

PMID- 23555447
TI  - Surgical Repair of Arteriovenous Fistula Associated with Iinfrarenal Aorto-iliac
      Aneurysm: Report of Two Contrasting Cases.
AB  - We present two cases of arteriovenous fistulas associated with aneurysms of the
      infrarenal aorta or common iliac artery. A definitive diagnosis is sometimes
      difficult given the varied and unclear presentation. However, with the correct
      preoperative diagnosis, mortality can be reduced. Both cases, being reported
      here, were diagnosed preoperatively and underwent alternate surgical repairs. One
      case was treated by aortic exclusion, whereas the second case was treated by
      primary closure of the fistula. Repair techniques were chosen based on acuity of
      presentation. Given our experience with these two cases, we conclude that direct
      closure is possible but dependent on the chronicity of the lesion.

PMID- 23555448
TI  - Pseudoaneurysm in the Left Groin due to Ruptured Knitted Dacron Graft.
AB  - An 82-year-old man was admitted to our institution with a painful pulsating mass
      in the left groin. He had undergone bypass surgery with a bifurcated Cooley
      double velour knitted Dacron graft to treat aorto-iliac occlusive disease 21
      years previously. Computed tomography demonstrated a 35-mm pseudoaneurysm near
      the distal anastomosis site of the graft. Opening the aneurysm revealed that the
      graft was disrupted along the guideline. We resected the aneurysm and interposed
      an expanded polytetrafluoroethylene (ePTFE) graft. Vascular surgeons should
      consider that grafts can fail in patients with long-term prosthetic grafts.

PMID- 23555449
TI  - Surgical outcome of two difficult cases with predominant proximal pulmonary
      artery lesions of chronic thromboembolic pulmonary hypertension.
AB  - Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension
      (CTEPH) is still challenging. The outcome of patients with proximal pulmonary
      artery disease is generally better than that of a distal lesion. However, we
      experienced poor results in two difficult cases having predominant proximal
      lesions even after effective PEA. Both of them had a long-time history of CTEPH
      and preoperative condition was critical. Although relatively large amount of
      thickened intima with massive thrombi were extracted from the proximal pulmonary
      arteries, they required postoperative percutaneous cardiopulmonary support due to
      residual pulmonary hypertension. Both of them finally died from pulmonary
      bleeding and adult respiratory distress syndrome.

PMID- 23555450
TI  - Transient thrombocytosis after endovenous laser treatment for primary varicose
      vein of the lower extremity.
AB  - We presented a case of a completely occluded great saphenous vein and transient
      thrombocytosis following endovenous laser treatment (EVLT) for primary varicose
      veins of the lower extremity. A 54-year-old man with a left saphenous varicose
      vein underwent EVLT surgery. Twelve-watt laser irradiation was delivered over the
      length of 33 cm of the saphenous vein. The cumulative exposure was 1042 J. Nine
      days after treatment, the platelet count increased up to 610 ? 10(3) /mm(3) and
      returned to normal after 2 months. A complete occlusion of the great saphenous
      vein commonly occurs after EVLT, but no case of transient thrombocytosis has been
      reported.

PMID- 23555451
TI  - A combined open and endovascular approach to treat a persistent sciatic artery
      aneurysm in an obese patient.
AB  - Persistent sciatic artery is a relatively uncommon peripheral vascular
      malformation of the lower extremity arterial blood supply that is often
      misdiagnosed. We present a case report of a 52-year-old, obese female who
      presented to our center with symptoms of lower extremity ischemia. We describe a
      novel approach combining open and endovascular techniques for the treatment of a
      persistent sciatic artery aneurysm, providing maximal benefit, while minimizing
      potential complications due to her co-morbidities.

PMID- 23555452
TI  - Current reconstructive techniques following head and neck cancer resection using
      microvascular surgery.
AB  - Various techniques have been developed to reconstruct head and neck defects
      following surgery to restore function and cosmetics. Free tissue transfer using
      microvascular anastomosis has transformed surgical outcomes and the quality of
      life for head and neck cancer patients because this technique has made it
      possible for surgeons to perform more aggressive ablative surgery, but there is
      room for improvement to achieve a satisfactory survival rate. Reconstruction
      using the free tissue transfer technique is closely related to cardiovascular
      surgery because the anastomosis techniques used by head and neck surgeons are
      based on those of cardiovascular surgeons; thus, suggestions from cardiovascular
      surgeons might lead to further development of this field. The aim of this article
      is to present the recent general concepts of reconstruction procedures and our
      experiences of reconstructive surgeries of the oral cavity, mandible, maxilla,
      oropharynx and hypopharynx to help cardiovascular surgeons understand the
      reconstructions and share knowledge among themselves and with neck surgeons to
      develop future directions in head and neck reconstruction.

PMID- 23555453
TI  - Enhanced neovascular formation in a novel hydrogel matrix consisting of citric
      Acid and collagen.
AB  - BACKGROUND: Three-dimensional regenerative tissue with large bulk generally
      requires blood perfusion through a vascular network to maintain its viability,
      and one promising approach is induction of neovascular growth from the recipient
      bed into the tissue. To induce ingrowth of a vascular network, it is necessary to
      furnish the regenerative tissue with a scaffold structure for neovasculature and
      a delivery system for an angiogenic growth factor. As such a scaffold structure,
      the present study created novel hydrogel materials by chemically cross-linking
      alkali-treated collagen (AlCol) with trisuccinimidyl citrate (TSC). MATERIALS AND
      METHODS: Many prototypes, consisting of several concentrations of TSC and AlCol,
      were implanted into the subfascial space of the rat rectus muscle, and 7 days
      later, the implanted materials were excised for histological analysis. Cross
      sections were stained and neovascular development in the materials was evaluated
      by measuring vessel density, length and number of joints and branches. RESULTS:
      Significant ingrowth of vascularized granulation was observed in some materials,
      which surpassed the angiogenic ability of Matrigel(TM). Further, combination with
      basic fibroblast growth factor (bFGF) significantly increased the vascular
      formation in these gels. CONCLUSIONS: The TSC-AlCol gel functioned as a favorable
      scaffold for neovascular formation and also as a reservoir for controlled
      delivery of bFGF.

PMID- 23555454
TI  - Preoperative Non-ambulatory Status Predicts Poor Outcome after Below Knee Bypass
      Surgery.
AB  - OBJECTIVE: To identify the outcome of below knee bypass that focuses on the
      functional status and to investigate whether preoperative functional status can
      predict these outcomes. MATERIALS AND METHODS: One hundred and fifty one limbs in
      one hundred and thirty two patients that underwent below knee bypass between 2004
      and 2008 were retrospectively reviewed. The patients were grouped as
      "ambulatory," "non-ambulatory transfer" and "non-ambulatory bedridden," according
      to their functional status. Clinical success was defined as the achievement of
      all of following end points; graft patency to wound healing, limb salvage for 1
      year or until death, maintenance of ambulatory status for 1 year, and survival
      for 6 months. The effect of preoperative ambulatory status was analyzed. RESULTS:
      The overall primary and secondary graft patency, limb salvage and survival at 1
      year were 76.3%, 81.8%, 89.1% and 84.1%, respectively. The overall success rate
      was 62.0%. Clinical success rates for the ambulatory and non-ambulatory groups
      were 75.6% and 34.9% (P = 0.0009, OR: 4.4; 95% CI: 1.8-10.6). CONCLUSIONS: Bypass
      surgery is justified for maintaining the independent status of ambulatory
      patients. On the other hand, the high likelihood of poor outcomes for non
      ambulatory patients must be considered before performing bypass surgery.

PMID- 23555455
TI  - Indicators of survival after open repair of ruptured abdominal aortic aneurysms
      and an index for predicting aneurysmal rupture potential.
AB  - BACKGROUND: The aims of this study were to assess variables associated with
      survival in patients undergoing ruptured abdominal aortic aneurysm (RAAA) repair
      and to develop an index other than the aneurysmal diameter to predict rupture
      potential. METHODS: This study included 43 consecutive patients who underwent
      open surgery for RAAAs. RESULTS: The mortality rate was 18.6% (8/43). The ratio
      between the maximum aneurysmal diameter and the length (along the central axis)
      from the aneurysmal neck to the point at which the diameter was three-fourth of
      the maximum aneurysmal diameter was used as an index to predict aneurysmal
      rupture potential. The index score was 2.7 +/- 1.2 in the RAAA and 1.9 +/- 0.9 in
      the EAAA (p = 0.018). For aneurysms of <= 6-cm diameter, the index score was 3.0
      +/- 1.0 in the RAAA and 1.8 +/- 0.9 in the EAAA (p = 0.03). All patients in the
      EAAA except one had an index score of < 2.3 and 6 of the 7 patients with RAAA had
      a score of > 3. CONCLUSIONS: The results suggest that patients with AAA having
      scores of > 3 are at high risk of rupture. This index would be useful for
      decision making regarding repair of AAA, especially in the borderline cases.

PMID- 23555456
TI  - Early outcomes of endovascular aneurysm repair for abdominal aortic aneurysm:
      first preliminary report of national hospital organization network study in
      Japan.
AB  - OBJECTIVE:  PATIENTS AND METHODS: In order to assess the early outcomes of
      endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) in the
      Japanese population, a total of 183 patients who had EVAR at eight medical
      centers of the National Hospital Organization were retrospectively reviewed and
      registered. The mean number of registered cases in each center was 23 +/- 17 (4
      50 cases). Patient characteristics were male sex, 84%; mean age, 77 years; age >=
      80 years, 40%. RESULTS: In-hospital mortality was one case (0.5%). Endoleaks were
      observed at the end of the procedure in 35 patients (19%: type I: n = 4, II: n =
      22, III, n = 3, IV: n = 6). Early morbidity included delayed wound healing or
      infection (n = 7), deterioration of renal dysfunction (n = 3), stroke (n = 2),
      postoperative bleeding (n = 2), gastrointestinal complications (n = 2), and
      peripheral thromboembolism (n = 2). Eleven late deaths included one of unknown
      cause and six cardiovascular causes at a mean follow up of 1.0 year. Survival
      rates of freedom from all causes of death and from aneurysm-related death at one
      year were 95.4% +/- 1.7% and 99.5% +/- 0.5%, respectively. INTERPRETATION:
      Although registered patients carry a variety of risks, early outcomes were
      satisfactory. EVAR is an acceptable alternative treatment modality for treating
      AAA.

PMID- 23555457
TI  - Outcome of the external carotid artery following carotid endarterectomy with
      added external carotid artery eversion endarterectomy.
AB  - OBJECTIVE: To study the results of eversion endarteterctomy of the external
      carotid artery (ECA) performed as part of standard CEA at a tertiary referral
      center using duplex ultrasonography. MATERIALS AND METHODS: Sixty patients (18
      women and 42 men) who underwent 65 carotid endarterectomies at Waikato Hospital
      between January 2006 and July 2007 for significant internal carotid artery (ICA)
      disease were studied. The procedure also included eversion endarterectomy of the
      ECA with sharp transection at eversion end point. Preoperative and postoperative
      duplex scans were performed for all patients using Acuson (USA) ultrasound
      machine and by one sonographer. Postoperative follow-up scans at periods between
      6 weeks and 18 months were reviewed and analyzed with Ascer et al. Doppler
      ultrasound-scan peak systolic velocity (PSV) criteria. RESULTS: Preoperative
      scans revealed significant bifurcation disease involving both ICA and ECA in all
      patients. The first post operative scan, done six weeks post-operatively,
      revealed one incomplete ECA endarterectomy, resulting in moderate (50%-74%)
      stenosis, while the rest had no evidence of residual ECA disease at the site of
      ECA endarterectomy. Over the post-operative period, sixteen (24.6%) ECA lesions
      and no occlusions were reported. The degree of ECA stenosis ranged from moderate
      to severe with PSVs ranging from 120 to 461 cm per second. All ECA lesions were
      ostial. Only 3 (18.7%) lesions were detected in the first nine months post
      operatively. Fifteen lesions were smooth and regular on duplex, while one had
      features of irregular residual stenosis. Eight (50%) were isolated ECA lesions,
      while the rest was associated with either ICA restenosis or occlusion.
      CONCLUSION: ECA disease progression detected by Duplex ultrasound following
      eversion endarterectomy, as a part of CEA, commonly happens after 9 months and
      results in recurrent ECA stenosis, in most cases. Timing and features of the
      lesions suggest an intimal reaction as the aetiology in most cases. Eversion
      endarterectomy of the ECA does not predispose to ECA occlusion.

PMID- 23555458
TI  - Three-dimensional CT Venography: A Diagnostic Modality for the Preoperative
      Assessment of Patients with Varicose Veins.
AB  - OBJECTIVE: We preoperatively assessed varicose veins by means of computed
      tomography (CT) with contrast injection in the veins of the lower extremity (CT
      venography). This paper reports the procedures, results and implications of CT
      venography from the surgical aspect. METHODS: A total of 48 legs in 39 patients
      were examined. Contrast medium was diluted ten-fold and injected into the lower
      extremity veins, often using a dual route of injection. The images were
      reconstructed with the volume-rendering method. RESULTS: CT venography clearly
      visualized the veins with a small amount of contrast medium and facilitated the
      identification of anatomy that was not suitable for passing the stripper. In
      addition, CT venography helped identify unusual types of varicose veins or
      uncommon sites of inflow of small saphenous veins. Such information was helpful
      for avoiding unexpected vascular injury or for minimizing skin incision. Dual
      route injection was beneficial to minimize the blind zones. Doppler ultrasound
      could be more focused on hemodynamic assessment and determination of incision
      sites. CONCLUSIONS: CT Venography is feasible in all cases of varicose veins.
      When performed in conjunction with ultrasonography, it appears to facilitate the
      safe and efficient treatment of various types of varicose veins.

PMID- 23555459
TI  - Skin perfusion pressure measurement to assess improvement in peripheral
      circulation after arterial reconstruction for critical limb ischemia.
AB  - AIM: To assess the utility of skin perfusion pressure (SPP) measurement in
      evaluating the outcome of vascular constructions for critical limb ischemia (CLI)
      patients. METHODS: We retrospectively studied 19 lower limbs in 18 patients who
      underwent arterial reconstruction for CLI from whom SPP measurements had been
      obtained pre- and postoperatively between 2008 and 2010. Six limbs whose ulcers
      had healed postoperatively were classified into group H, 7 limbs whose ulcers had
      not healed into group U, and 6 limbs without ulcers into group N. SPP values were
      compared among these groups. RESULTS: The preoperative SPP values in all groups
      were <30 mmHg, without significant differences among the groups. The SPP values
      in groups H and N significantly improved after operation, and those in group U
      were significantly lower than those in the other groups. CONCLUSIONS: SPP
      measurement before and after arterial reconstruction is useful to assess
      improvement in tissue circulation and to predict the likelihood of wound healing.
      An SPP value >=30 mmHg was considered necessary for wound healing, supporting the
      findings of the few reports in the literature on the usefulness of SPP for
      assessing vascular reconstruction effects on ulcer wound healing.

PMID- 23555460
TI  - Atypical giant cell arteritis presenting as lack of a pulse in the upper
      extremity.
AB  - Giant cell arteritis (GCA), an inflammatory vasculopathy that preferentially
      affects medium-sized and large arteries, has diverse symptoms and varied clinical
      courses that can make the diagnosis difficult. We describe a 75-year-old woman in
      whom GCA presented as lack of a pulse in the right arm. Although steroid therapy
      is generally effective for treating GCA, surgical intervention provides a biopsy
      specimen for a definitive diagnostic study and restores blood flow in the
      affected limb. GCA should be considered along with atherosclerosis in cases of
      occlusive disease of the upper extremity, especially if the patient is an elderly
      woman.

PMID- 23555461
TI  - Complete Rupture of Polytetrafluoroethylene-covered Endoprosthesis after
      Exclusion of a Popliteal Aneurysm.
AB  - Popliteal artery aneurysm (PAA) is the most commonly reported peripheral artery
      aneurysm. The usual treatment is exclusion bypass with a saphenous vein. However,
      the availability of medium size covered stent graft is an attractive option. By
      performing this procedure percutaneously, we can shorten the hospital stay of the
      patient. Favourable early and long-term results have been reported; however,
      little is known about the durability of the procedure. Given the mobile location
      of the stent-graft close to the knee joint, graft damage can be expected. We
      describe a case of complete rupture of a Viabahn((r)) endoprosthesis which was
      inserted to exclude a PAA.

PMID- 23555462
TI  - Two-stage Surgery for Double Infected Aneurysms in the Infrarenal Abdominal and
      Descending Thoracic Aorta.
AB  - A 61-year-old man complaining of lumbago and high-grade fever was admitted to our
      institution. Computed tomography (CT) revealed a saccular aneurysm in the
      infrarenal abdominal aorta and blood culture results were positive for
      Streptococcus pneumoniae. He was diagnosed with infected abdominal aortic
      aneurysm, and antibiotic therapy was initiated. Follow-up CT demonstrated a
      rapidly-enlarging abdominal aortic aneurysm and a newly-developed descending
      thoracic aortic aneurysm. For this case, two-stage surgery consisting of extra
      anatomical bypass and in-situ reconstruction using rifampicin-soaked Dacron graft
      was performed after an interval of 37 days. The patient was discharged 14 days
      after the second surgery without any complications.

PMID- 23555463
TI  - Traumatic innominate artery pseudoaneurysm in the setting of a bovine arch.
AB  - Blunt traumatic injury of the innominate artery occurs infrequently but is
      commonly lethal. Bovine aortic arch anatomy is a predisposition to this injury.
      Clinical findings, chest X-ray, and computerized tomography may suggest the
      diagnosis, and it may be confirmed with angiography. Both interposition and
      bypass grafting are operative repair methods of choice. EEG monitoring confirms
      cerebral perfusion, thereby allowing the deferment of shunts and cardiovascular
      bypass with hypothermic arrest. We report a case of traumatic innominate artery
      pseudoaneurysm in the setting of "bovine aortic arch" anatomy, together with
      multiple associated injuries, including descending aorta transection. We also
      review the current literature on the topic.

PMID- 23555464
TI  - Focal Renal Arterial Fibromuscular Dysplasia Demonstrated via Intravascular
      Ultrasound Image.
AB  - A young male suffering from renovascular hypertension was admitted. His initial
      arteriogram highlighted a focal stenosis of the right renal artery. His
      intravascular ultrasound (IVUS) revealed increasing medial layer thickness
      accompanied by a mixture of both high and low echoic materials in this layer.
      There was also mild thickening of the intimal layer. The diagnosis of medial
      fibroplasia and intimal fibromuscular dysplasia (FMD) was made. Balloon
      angioplasty decreased the volume of dysplastic tissue. The IVUS images
      facilitated both the initial diagnosis of focal renal arterial stenosis and the
      evaluation of the mechanism of dilatation by angioplasty.

PMID- 23555465
TI  - Magnetic resonance angiography of the aorta.
AB  - Magnetic resonance angiography (MRA) is capable of imaging arteries in the half
      to whole body by a single acquisition without a nephrotoxic contrast medium, and
      acquired images can be reconstructed into a specific cross-sectional view in an
      arbitrary directions. MRA is applicable for vessels non-reachable by a catheter
      approach, and collateral vessels can be fully visualized. Since MRA is minimally
      invasive with no exposure to ionized radiation, it can be repeatedly applied for
      follow-up. However, there are also disadvantages: the temporal and spatial
      resolutions are inferior to those of X-ray angiography, and, at present, it
      cannot be used as a guide for intervention. Moreover, gadolinium administrations
      may cause NSF in patients who have lost renal function, as a new risk.
      Accordingly, strict consideration is required for an indication of its
      application. Development of non-contrast MRA and evaluation of the wall itself
      may draw more attention in the future. Plaque imaging is being routinely
      performed nowadays, and the measurement of vascular wall shear stress, which has
      a close association with arteriosclerosis, may become possible by utilizing the
      time-resolved phase-contrast method capable of measuring the time-resolved
      velocity vectors of blood flow throughout the body. (*English Translation of J
      Jpn Coll Angiol, 2009, 49: 503-516.).

PMID- 23555466
TI  - Simultaneous Evaluation of the Whole Aorta and Artery of Adamkiewicz by MDCT.
AB  - Recent technical advancement has allowed simultaneous visualization of the artery
      of Adamkiewicz and whole aorta by multidetector-row-CT (MDCT). Although we could
      visualize the artery of Adamkiewicz in a high percentage of patients with
      thoracoabdominal aortic diseases, CT scanning with an adequate protocol and
      careful post-processing are necessary for accurate evaluation. Noninvasive
      evaluation of the artery of Adamkiewicz is useful in planning surgery.
      Preoperative evaluation of the intercostal arterial level from which the artery
      of Adamkiewicz originates is reportedly important for preventing postoperative
      spinal cord ischemia. Although, the usefulness of preoperative information on the
      artery of Adamkiewicz is still controversial, preoperative identification of the
      artery of Adamkiewicz by imaging has gradually spread since our first report, and
      has been included in preoperative evaluation items at many institutions,
      revealing its contribution to improvement in surgical results. (*English
      Translation of J Jpn Coll Angiol, 2004, 44: 693-699.).

PMID- 23555467
TI  - Treatment strategy for acute type a aortic dissection complicated with organ
      ischemia.
AB  - OBJECTIVE: We report our current treatment strategy for acute type A aortic
      dissection with organ ischemia as well as notable findings in our experience.
      MATERIALS AND METHODS: Among 101 cases of acute type A aortic dissection, 25 had
      organ ischemia. Malperfusion was assessed at the aorta, proximal portion of the
      branch, organ parenchyma, and organ function by means of multiple modalities,
      including transesophageal echocardiography (TEE), near-infrared spectroscopy, and
      physical examinations. It was assessed every time the perfusion status was
      altered. RESULTS: There were three operative deaths and one late hospital death.
      Uncertainty of symptoms and inadequate preoperative assessment in an emergent
      situation indicated the necessity of an overall check-up of organ ischemia in the
      operating room on a routine basis. Multi-modality assessment including TEE was
      helpful for this purpose. Two cases indicated that recovery of a true lumen could
      be inadequate despite true lumen perfusion including central cannulation.
      Thrombus in the false lumen appeared to be responsible. CONCLUSIONS: To solve
      practical problems in treating acute type A dissection with organ ischemia, real
      time information on organ perfusion is important for detecting the presence of
      malperfusion, making an appropriate strategy, and immediately assuring the
      efficacy of the means taken.

PMID- 23555468
TI  - Cardiac and Aortic Reoperation for Patients with Functional Grafts after CABG.
AB  - OBJECTIVE: Late cardiac and aortic reoperation after CABG is indispensable for
      patients with atherosclerotic disease, but reoperations are still associated with
      high morbidity rates. PATIENTS AND METHODS: Between January 2002 and December
      2010, 459 patients underwent coronary artery bypass grafting. Six patients
      (males; mean age, 65.0 +/- 5.7 years) with previous arterial bypass grafts (mean,
      2.8 +/- 1.2 per patient) required reoperation for cardiac and aortic disease (3,
      valvular disease; 3, acute type I aortic dissection) during long-term follow-up.
      The mean interval between the initial operation and reoperation was 5.4 +/- 2.0
      years. Grafts visualized by preoperative enhanced computed tomography were
      harvested as pedicles and clamped for myocardial protection. The total arch or
      ascending aorta was replaced in three patients. The aortic valve was replaced in
      two patients, and the aortic and mitral valves were replaced in one. RESULTS:
      Durations for surgery, total cardiopulmonary bypass, and cardiac ischemia were
      611.5 +/- 172.6, 223.2 +/- 88.4, and 133.4 +/- 58.0 minutes, respectively.
      Perioperative myocardial infarction did not develop, and all patients recovered
      uneventfully with no neurological deficits. CONCLUSION: Bypass grafts should be
      preoperatively visualized and carefully exposed. Cardiac damage must be avoided
      during reoperation after coronary artery bypass grafting.

PMID- 23555469
TI  - Impact of aggressive decongestion on the maintenance phase in combined physical
      therapy for lower extremity lymphedema.
AB  - OBJECTIVES: To evaluate the impact of initial aggressive decongestion (Phase 1)
      on the maintenance phase of complex physical therapy (CPT). MATERIALS AND
      METHODS: We reviewed 27 patients with unilateral and 3 patients with bilateral
      lower extremity lymphedema who started CPT between April, 2009 and October, 2010.
      Twelve patients elected to undergo in-hospital Phase 1 (Group I), while the other
      18 started CPT on an outpatient-basis without having Phase 1 (Group O). The
      extremity volume was assessed at the beginning of CPT, and then 3 and 6 months
      later. RESULTS: A significant reduction in extremity volume was achieved in each
      group after 6 months of CPT: from 9049 +/- 1912 mL at the beginning to 7771 +/-
      1486 mL (p = 0.0033) in group I; and from 7370 +/- 1392 mL to 7036 +/- 1241 mL (p
      = 0.0200) in group O. However, after 6 months, extremity volume reduction (-845
      +/- 1283 mL in group I vs. -404 +/- 370 mL in group O; p = 0.7672) and volume
      reduction rates (-23.6 +/- 22.7% in group I vs. -46.4 +/- 52.2% in group O; p =
      0.2564) did not differ significantly between the groups. CONCLUSION: Phase 1 did
      not have a significant impact on the maintenance phase in terms of control of the
      extremity volume for at least 6 months after the induction of CPT.

PMID- 23555470
TI  - Open repair of infra renal abdominal aortic aneurysms: a single center experience
      from the developing world.
AB  - INTRODUCTION: In the absence of endovascular aneurysm repair due to financial
      constraints, Abdominal Aortic Aneurysm (AAA) in Sri Lanka is managed exclusively
      by open surgery. We report our experience with open AAA repair with emphasis on
      peri-operative morbidity and mortality. METHODS: Seventy nine consecutive open
      AAA repairs were carried out between April 2004 and March 2010. A multiple
      regression model was used to identify predictors of significant peri-operative
      morbidity and mortality. RESULTS: Mean age of the study cohort was 68 years.
      There were 63 (80%) males and 16 (20%) females. Mean aneurysm diameter was 6.4
      (3.5-9.70) cm. Twenty seven (34%) underwent emergency surgical repair (group-1)
      while 52 (66%) had elective repair (group-2). The peri-operative mortality was
      10/27 (37%) in group-1, 4/52 (7.6%) in group-2, (p = 0.0035). Significant post
      operative morbidity was seen in 5/17 (29%) in group-1 and 7/48 (15%) in group-2,
      (p = 0.27). Aneurysm diameter >7 cm (p = 0.001), emergency repair (p = 0.004),
      history of smoking (p = 0.002), aortic cross-clamp time >60 minutes (p = 0.044),
      and need for post-operative ventilwation >24 hours (p = 0.024) were found to be
      independent predictors of peri-operative mortality or significant morbidity.
      CONCLUSION: Open aneurysm repair still has a strong place especially in the
      limited resource setting, with acceptable outcomes.

PMID- 23555471
TI  - Early and Long-term Effects of the Autologous Peripheral Stem Cell Implantation
      for Critical Limb Ischemia.
AB  - OBJECTIVE: Therapeutic angiogenesis by peripheral blood mononuclear cells (PB
      MNCs) implantation has been shown to be a safe and effective treating for
      critical limb ischemia (CLI). We herein report our investigation of the long-term
      efficacy of implantation of granulocyte-colony stimulating factor (G-CSF)-induced
      PB-MNCs to treat patients with CLI for which surgical bypass and/or percutaneous
      transluminal angioplasty are not possible. Methods and Methods : Eleven cases
      were enrolled in this study. Following an injection of G-CSF (250 ug/day) for 3
      days, PB-MNCs (1.1 +/- 0.5 * 10(10) including 1.5 +/- 0.2 * 10(7) CD34-positive
      cells) were harvested by apheresis and then injected into 13 ischemic limbs.
      RESULTS: Resting pain either diminished or improved in 10 cases (91%) at 4 weeks,
      and ulcer formation was cured in 6 out of 10 limbs (60%) after treatment. The
      time required to enhance the arteries at the level of foot-joint by angiography
      which was performed in the abdominal aorta was shortened by 1 month (10 +/- 4
      seconds) and 6 months (12 +/- 1) compared with the pretreatment time (15 +/- 5).
      Three patients died after treatment, and the actuarial survival rate at 3 years
      was 73%. Freedom from major amputation at 3 years was 92%. CONCLUSION: The local
      injection of G-CSF-induced PB-MNCs showed striking early and long-term effects.

PMID- 23555472
TI  - A case of a mycotic aneurysm of the superficial femoral artery infected by mixed
      bacterial species.
AB  - A 65-year-old woman, recently diagnosed with diabetes, presented with fever and a
      warm, pulsatile, tender mass over the medial aspect of her left thigh. She gave a
      history of diarrhea two weeks earlier. All lower limb pulses were present. CRP
      was 18.3 mg/l with evidence of neutrophil leukocytosis. Contrast angiography
      demonstrated a saccular aneurysm in her left superficial femoral artery (SFA).
      The aneurysm and surrounding infected, necrotic muscle was excised, and the limb
      was re-vascularized in-situ. Cultures from the aneurysmal wall grew both coliform
      bacilli and staphylococcus aureus. A mycotic aneurysm of the SFA, following a
      previous gastroenteritis, harbouring both staphylococcal and coliforms, makes
      this case unique.

PMID- 23555473
TI  - A Case of LMT Reconstruction Using Superficial Femoral Artery Graft in the
      Patient with Type A Acute Aortic Dissection.
AB  - A 76-year-old woman underwent a Bentall procedure for acute aortic dissection. A
      dissection involving half of the proximal portion of the left main coronary
      artery trunk was confirmed. The dissected site was resected, and a section of the
      superficial femoral artery was harvested and used as an interposition graft
      between conduit and the residual left main trunk. Two years after surgery, the
      graft remained well patent. If the coronary dissection involves only the left
      main artery trunk, the superficial femoral artery should be used as an artery
      graft for the anatomical reconstruction, potentially leading to better early and
      late outcomes.

PMID- 23555474
TI  - The management of persistent sciatic artery aneurysm with lower extremity
      ischemia: a case report.
AB  - We report a case of lower extremity ischemia caused by a persistent sciatic
      artery aneurysm . The patient was successfully treated with a ringed expanded
      polytetrafluoroethylene (ePTFE) graft and recovered uneventfully. The graft was
      patent during the follow-up and no signs of kinking or restenosis.

PMID- 23555475
TI  - Repeat Operation for Pseudoaneurysm of Left Ventricular Outflow in a Patient with
      Concomitant Takayasu's Arteritis and Marfan Syndrome.
AB  - We describe concomitant Marfan syndrome and Takayasu's arteritis complicating a
      pseudoaneurysm of the left ventricular outflow that developed after aortic root
      reconstruction. A patient was admitted with a high fever four months after
      initial root reconstruction that included valve sparing (reimplantation) as well
      as coronary artery reconstruction using a Carrel's button technique. Computed
      tomography revealed a pseudoaneurysm at the posterior side of the aortic root. We
      applied a modified Bentall procedure including coronary artery reconstruction
      using the Piehler technique. Pathological assessment of a specimen of the aorta
      revealed no central medial necrosis, but significant lymphocytic infiltration and
      thick fibrous adventitia indicating Takayasu's arteritis. This case was unique in
      terms of having simultaneous Takayasu's arteritis and cardiovascular
      manifestations of Marfan syndrome that were surgically treated.

PMID- 23555476
TI  - A staged total aortic replacement with combined endovascular and open surgery:
      report of a case.
AB  - For a 75 year-old man with extensive aortic aneurysm, who had undergone a
      previous infra-renal abdominal Y-graft, a staged replacement of remaining
      segments was performed. A hybrid procedure of open-laparotomy debranching of
      visceral branches and endovascular stentgraft insertion in the thoracoabdominal
      aorta was performed first, followed by subsequent direct replacement between the
      proximal ascending and distal arch using cardiopulmonary bypass. Three months
      thereafter dissection of enlarged proximal descending aorta occurred, for which
      we performed an emergent endovascular stentgraft deployment which bridged
      "elephant trunk" of the arch graft and the previous stentgraft. Consequently
      total aortic replacement was successfully accomplished without any neurological
      sequela.

PMID- 23555477
TI  - Emergent thoracic endovascular aortic repair for acute type-B aortic dissection
      with malperfusion by matsui-kitamura stent graft.
AB  - Acute type-B aortic dissection with malperfusion is a serious cardiovascular
      condition associated with high morbidity and mortality. Recent studies have
      investigated the efficacy of thoracic endovascular aortic repair (TEVAR) as
      treatment for acute aortic dissection. In this report, we present a case of acute
      type-B aortic dissection complicated with malperfusion, which was successfully
      treated with emergent TEVAR for entry closure by a Matsui-Kitamura stent graft
      (MKSG). MKSG is a flexible custom-made curved stent graft. The main advantages of
      MKSG for emergent TEVAR include flexibility, shape, and small profile when
      compressed.

PMID- 23555478
TI  - Conservative therapy for surgically untreatable extensive arteriovenous
      malformation from the lower extremity to the pelvis with secondary consumptive
      coagulopathy.
AB  - We present a woman with surgically untreatable extended arteriovenous
      malformations (AVM) and consumptive coagulopathy, which had been controlled by
      conservative compression and anticoagulation therapies for 17 years. At age 13,
      she was diagnosed with extended AVM in the entire left leg and pelvis. At age 16,
      limited surgical resection of the enlarged superficial vein in the left calf was
      performed for persistent leg pain. One year later, anticoagulation therapy was
      performed for massive bleeding from hemorrhoids due to AVM and coagulopathy.
      Despite its intractability, her condition has been favorably controlled with
      conservative methods, including compression and anticoagulation therapies.

PMID- 23555479
TI  - Surgical treatment for aortic coarctation with chronic type B dissection: report
      of a case.
AB  - The aim of this paper is to report a rare case of aortic coarctation with type B
      aortic dissection. A 37 year-old man had sudden, intense back pain. Enhanced
      computed tomography revealed aortic coarctation (CoA) at the proximal descending
      aorta and acute type B aortic dissection just distal to the CoA. The dissecting,
      descending aortic aneurysm had expanded to a maximal diameter of 52 mm. The
      aortic coarctation was resected and then the descending aorta was replaced with
      prosthetic grafts in an uneventful procedure. Surgical repair resulted in a good
      outcome.

PMID- 23555480
TI  - Abdominal aortic disease caused by penetrating atherosclerotic ulcers.
AB  - OBJECTIVE: Penetrating atherosclerotic ulcer (PAU) of the aorta is defined as an
      atherosclerotic lesion with ulceration of the aortic intima and media and rupture
      of the internal elastic lamina. PAU induced aortic dissection, aortic rupture,
      and secular aortic aneurysm and typically occurs in elderly hypertensive patients
      with severe atherosclerosis. Although it has been reported that atherosclerosis
      similarly occurs in the abdominal aorta, its natural history and treatment are
      still unclear. This study investigated the clinical features, natural history,
      and treatment of PAU of the abdominal aorta. METHOD: Between April 2006 and March
      2009, 4 diagnoses of PAU in the abdominal aorta were made by computed tomography
      (CT) and magnetic resonance imaging (MRI). These 4 cases were analyzed along with
      61 previously reported cases from the literature with diagnoses of PAU in the
      abdominal aorta, aortic rupture, and isolated abdominal aortic dissection over
      the past 15 years, giving a total of 65 cases. RESULTS: The patients were men
      with an average age of 63.5 years. All 4 had hypertension, and 2 had concomitant
      coronary artery disease. Two patients were asymptomatic, and the other 2 were
      symptomatic and transmural rupture had occurred. All diagnoses were made by CT
      and MRI. All 4 patients underwent open surgery with a knitted Dacron graft, with
      no postoperative deaths. In the literature, 53% of cases were symptomatic,
      including pain (40%, n = 26), shock (4.6%, n = 3), and lower limb embolism (9.2%,
      n = 6). The remaining 40% of cases were asymptomatic (n = 26). Six patients were
      treated medically, while 58 patients underwent surgery, with 2 postoperative
      deaths. CONCLUSION: We suggest that surgical treatment (open surgery or
      endovascular stent grafting) should be performed to prevent an aortic catastrophe
      such as intramural hematoma, dissection, or rupture. (English translation of Jpn
      J Vasc Surg 2010; 19: 723-730.).

PMID- 23555481
TI  - Surgical treatment for thoracic aneurysms: comparison of stent grafting and open
      surgery.
AB  - OBJECTIVES: Early and mid-term results of stent graft (SG) treatment for thoracic
      aortic aneurysms (thoracic endovascular aneurysm repair: TEVAR) were
      retrospectively compared with open surgical treatment. METHODS: The records of
      213 patients in whom single thoracic aortic aneurysm repairs had been performed
      in our department from January 2006 through August 31, 2009 were reviewed. Acute
      aortic dissection was excluded. Each case was reviewed for indications for TEVAR
      from an anatomical standpoint. Among 62 cases in which TEVAR was indicated, 30
      (SG group) were treated by TEVAR and 32, by open surgery (OP group). Early and
      mid-term results were analyzed retrospectively in both groups. RESULTS: There
      were no operative deaths in either group. The SG group demonstrated significantly
      less operative bleeding, a shorter operative time, and shorter postoperative
      hospital stay compared with the OP group. There were 3 deaths in the SG group and
      4 in the OP group, which occurred within an average of 656.4 days during the
      follow up period. The 3 year actuarial survival rate was 88.7% in the SG group
      and 87.1% in the OP group, and there were no significant differences between the
      groups. CONCLUSION: Although early and mid-term results of TEVAR and open surgery
      were similar, TEVAR is generally less invasive and may be preferable for high
      risk patients, compared with open surgical repair. (English Translation of Jpn J
      Vasc Surg 2010; 19: 51-56.).

PMID- 23555482
TI  - Technical challenges in endovascular repair of complex thoracic aortic aneurysms.
AB  - BACKGROUND: Endovascular aneurysm repair has gained widespread acceptance, and
      there has been a significant increase in the number of aneurysms treated with
      stent grafts. However, the endovascular technique alone is often not appropriate
      for anatomically complex aneurysms involving the neck branches. We used the TAG
      stent for thoracic aortic aneurysms (TAA), and report our initial results.
      PATIENTS AND RESULTS: We deployed 80 TAG stents in 65 patients electively treated
      with TAA between June 2006 and June 2008. Thoracic endovascular aneurysm repair
      (TEVAR) was performed in 45 cases of descending aortic aneurysm with no morbidity
      or mortality. A combination of open surgery and TEVAR was performed in 11 out of
      20 cases with aneurysms of the aortic arch. The prior total arch replacement and
      elephant trunk procedure was performed in 3 cases with dilated ascending aorta,
      total debranching from ascending aorta with sternotomy in 5, and carotid-carotid
      artery crossover bypass in 3 cases. Meanwhile, TEVAR with coverage of the left
      subclavian artery was performed in the remaining 9 distal arch cases. In 3 cases
      with extremely short necks, a 0.018" guide wire was inserted percutaneously in a
      retrograde manner through the common carotid artery (CCA) into the ascending
      aorta to place the stent graft in close proximity to the CCA (wire protection).
      In 1 of these 3 cases, the TAG stent was deployed through the CCA, and the 0.018"
      guide wire was used to deliver a balloon-expandable stent in order to restore the
      patency of the CCA. In arch and distal arch aneurysm cases, perioperative
      mortality and the incidence of stroke were both 5.0%; dissection of the ascending
      aorta was seen in one case (5.0%). CONCLUSION: As treatment for descending aortic
      aneurysms, TEVAR can replace conventional open repair. However, TEVAR for arch
      aneurysms has some problems, and further improvement is necessary. (English
      Translation of Jpn J Vasc Surg 2010; 19: 547-555.).

PMID- 23555483
TI  - Examination of Difference in the Proximal Anastomotic Site for Crus, Ankle
      Bypass: Common Femoral Artery vs Below the Knee Popliteal Artery.
AB  - OBJECTIVE: We evaluated the outcomes of bypass surgery for revascularization in
      cases of critical limb ischemia with the distal anastomotic site at or below the
      ankle; we focused on the differences in outcomes between 2 groups having
      different proximal anastomotic sites. PATIENTS AND METHODS: Out of 270 cases
      diagnosed with critical limb ischemia from January 2003 to October 2009, bypass
      surgeries with the distal anastomotic site at or below the ankle were performed
      on the limbs of 69 patients (75 limbs). These cases were classified on the basis
      of the proximal anastomotic sites: group F (n = 50) where the common femoral
      artery was the proximal anastomotic site and group P (n = 25) where the below
      knee popliteal artery was the site. RESULTS: The 5-year cumulative
      primary/secondary patency rates were 69.3%/81.8% for group F and 68.7%/84.9% for
      group P. The 5-year cumulative limb salvage rate was 97.9% in group F and 80.3%
      in group P. CONCLUSION: Among the cases reviewed, results were comparable between
      cases with the proximal anastomotic site at the below-knee popliteal artery and
      those with the site at the common femoral artery.

PMID- 23555484
TI  - Lowered postoperative ldl-c/hdl-C ratio reduces later cardiovascular events after
      abdominal aortic aneurysm surgery.
AB  - PURPOSE: To examine the relationship between the incidence of later
      cardiovascular events after abdominal aortic aneurysm (AAA) surgery and
      postoperative lipid levels. METHODS: Atherosclerotic risk factors including
      postoperative serum lipid levels were examined in 116 patients aged 70 or less
      undergoing an elective AAA surgery. Later cardiovascular events after AAA surgery
      occurred in 21 patients, including cerebral infarction (n = 4), catheter
      intervention or surgery for coronary artery disease (CAD) (n = 10) and other
      vascular disease. RESULTS: Postoperative cholesterol levels during the average
      follow-up period of 55.6 +/- 44.3 (months) were 49.0 +/- 15.7 (mg/dL) for high
      density lipoprotein cholesterol (HDL-C), 97.9 +/- 31.2 (mg/dL) for low-density
      lipoprotein cholesterol (LDL-C), which were both significantly improved compared
      to preoperative values (p <0.001). Cox hazard analysis indicated that preexistent
      CAD significantly increased in the risk for later cardiovascular events (hazard
      ratio 5.67; 95%CI 1.92-16.8; p = 0.002) and lowered postoperative LDL-C/HDL-C
      ratio <1.5 decreased in the risk after AAA surgery (hazard ratio 0.10; 95%CI 0.01
      0.83; p = 0.033). Patients with postoperative LDL-C/HDL-C ratio <1.5 (n = 22) had
      a significantly better cardiovascular event-free rate than those with that ratio
      >=1.5 (n = 94) (p = 0.014). CONCLUSION: Lowered postoperative LDL-C/HDL-C ratio
      <1.5 can decrease in the risk for later cardiovascular events after AAA surgery.
      These results may support the rationale for postoperative aggressive lipid
      modifying therapy.

PMID- 23555485
TI  - Clinical Study of Phlebitis Migrans and Incompetence of the Leg's Superficial
      Vein in Buerger Disease.
AB  - Three of four (75%) vein biopsy samples from four patients (all male, mean onset:
      age 33.0, mean biopsy: age 59.7) of chronic phase phlebitis migrans showed
      positive periodontal bacteria DNA under the PCR (polymerase chain reaction)
      method. Of the 24 cases of Buerger disease (22 males, 2 females, mean onset: age
      31.9, mean examination: age 62.6) that were investigated in our vascular
      laboratory, 65% of the patients suffered from moderate to severe varicose veins.
      Eight cases had a history of phlebitis migrans and three had an active ulcer or
      uncontrollable erosion in the foot. The rate of incidence was significantly
      higher than that of the well-matched control group. Other findings included one
      instance of deep vein thrombosis, and one instance of deep vein reflux. We could
      suggest that some intractable ulcer or erosion cases of Buerger disease may be
      complicated by superficial vein incompetence or other deep vein insufficiency. We
      also we need to check Buerger disease patients with duplex for vein reflux and
      other insufficiencies. Treatment of the varicose veins (including elastic
      stockings) was effective for all of the patients. (English Translation of Jpn J
      Phlebology 2011; 22: 25-31.).

PMID- 23555487
TI  - Hybrid repair combined with open surgery and endografting for lesions in right
      aortic arch: report of three cases.
AB  - Three cases with lesions in the right aortic arch (RAA) are presented. For two
      patients, whose RAA contained a retroesophageal segment, the primary treatment
      was total arch replacement (TAR) for acute type A dissection or severe arch
      angulation with thoracic endovascular aneurysm repair (TEVAR) as second-stage
      surgery. The third patient, who had RAA with mirror image branching, underwent
      supra-aortic bypass followed by TEVAR. There was no operative mortality, but the
      condition of two patients who underwent TAR was complicated by bilateral
      recurrent nerve palsy, which can be critical. The combination of TEVAR and supra
      aortic bypass might thus be preferable for patients with RAA.

PMID- 23555486
TI  - Autologous peripheral blood-derived mononuclear cells induced by erythropoietin
      improve critical ischemic limbs.
AB  - PURPOSE: Efficient and secure collection of CD34+ cells are crucial for the
      angiogenic therapies. We have developed autologous peripheral blood-mononuclear
      cell (MNC) transplantation induced by erythropoietin (rhEPO) for critical
      ischemic limbs. METHODS: Seven patients, including five with arteriosclerosis
      obliterans, one with Buerger's disease and one with progressive systemic
      sclerosis, underwent ten cell therapies. The first administration of rhEPO was
      performed two weeks before apheresis, and the second administration and blood
      donation were performed one week before apheresis to activate bone marrow. MNCs
      including CD34+ cells, isolated from peripheral blood by apheresis, were
      immediately injected intramuscularly into ischemic limbs. RESULTS: The number of
      peripheral blood-CD34 + cells had significantly increased from 1.32 +/-
      0.83/microL, before the rhEPO induction, to 1.86 +/- 0.94/microL, before the
      apheresis. The number of transplanted MNCs ranged between 0.5 * 10(9) and 16.5 *
      10(9), and that of CD34+ cells, between 0.1 * 10(6) and 12.7 * 10(6), accounting
      for 0.02%-0.1% of MNCs. There were no serious complications. Finger ulcers with
      Buerger's disease were significantly improved one month after the
      transplantations, but the same or other ulcer(s) appeared 2-6 months later. Three
      patients had an improvement in rest pain, and one patient extended maximum pain
      free walking distance. CONCLUSIONS: Erythropoietin-induced autologous peripheral
      blood-MNC transplantation is a useful and safe alternative for ischemic limbs.

PMID- 23555488
TI  - A foot ulcer caused by the use of an angio-seal arterial closure device after
      percutaneous transluminal angioplasty: a case report.
AB  - Although the Angio-Seal arterial closure device is widely used for preventing
      bleeding and facilitating early ambulation after arterial puncture, it is also
      associated with unique complications, such as stenosis, occlusion, or peripheral
      embolism. We report the first case of a foot ulcer that developed 70 days after
      an Angio-Seal application. The collagen sponge component accidently positioned
      itself in the arterial lumen and was not absorbed. A foreign body reaction was
      observed microscopically. In patients with arteriosclerosis, the Angio-Seal
      device should be used carefully; post procedural monitoring is necessary after
      implantation.

PMID- 23555489
TI  - Simultaneous endovascular aneurysm repair and distal gastrectomy in a patient
      with concomitant abdominal aortic aneurysm and advanced gastric cancer.
AB  - The optimal surgical management of patients with concomitant abdominal aortic
      aneurysm (AAA) and gastrointestinal malignancy remains controversial. A 79 year
      old man who presented with hematemesis was found to have advanced gastric cancer
      concomitant with infrarenal AAA. The patient underwent simultaneous endovascular
      aneurysm repair (EVAR) and distal gastrectomy. The postoperative course was
      uneventful. The present case illustrates the clinical utility of EVAR for the
      high-risk patient with concomitant AAA and gastrointestinal malignancy.

PMID- 23555490
TI  - Preservation of aortic arch branches using chimney and sandwich stent grafts.
AB  - PURPOSE: To share our hybrid endovascular experiences using chimney or sandwich
      stent grafts for acute aortic arch pathologies. METHODS: Hybrid procedures for a
      distal aortic arch aneurysm and an ascending anastomotic aortic aneurysm rupture
      were reported. Right to left common carotid and left axillar artery bypasses were
      located. Covered stents were inserted into the inominate artery, with the flow
      proximal end located in the ascending (standard chimney) or the descending aortic
      stent graft (retrograde sandwich). RESULTS: Both cases had no signs of brain
      ischemia. Aneurysms are decreasing in size. CONCLUSION: Chimney and sandwich
      techniques were technically feasible in the complex and acute situations.

PMID- 23555491
TI  - Iatrogenic Acute Aortic Dissection during Percutaneous Coronary Intervention for
      Acute Myocardial Infarction.
AB  - Iatrogenic acute aortic dissection during percutaneous coronary intervention is
      an extremely rare, but critical complication. Localized aortic dissections have
      been treated by sealing the entry with a coronary stent. Extensive dissections
      may require a surgical intervention. We present a case of type A extensive aortic
      dissection occurring during angioplasty of the left circumflex artery for acute
      myocardial infarction. This iatrogenic aortic dissection required emergent
      surgical repair with supracoronary replacement of the ascending aorta.

PMID- 23555492
TI  - Intrathoracic left subclavian artery aneurysm: report of a case.
AB  - Aneurysms of the intrathoracic subclavian artery are extremely rare. A 74 year
      old man was referred to our hospital with an abnormal chest X-ray film. Contrast
      computed tomography revealed an intrathoracic left subclavian artery aneurysm.
      Via left 4th posterolateral thoracotomy, the aneurysm was exposed under systemic
      deep hypothermia and circulatory arrest. The distal arch was replaced with a 26
      mm single-branched graft and the left subclavian artery was reconstructed with a
      10 mm graft.

PMID- 23555493
TI  - Endovascular stenting for left subclavian venous stenosis for a hemodialysis
      patient with a persistent left superior vena cava.
AB  - A persistent left superior vena cava (PLSVC) is the most common thoracic venous
      anomaly, and we should be aware of its existence. We encountered a case of
      significant left arm swelling due to recurrent left subclavian venous stenosis in
      a hemodialysis patient with a PLSVC. Endovascular stent placement was performed
      safely and effectively for the stenosis employing the pull-through technique, in
      which a guidewire was passed from the left internal jugular vein to the access
      vein. On the following day, left arm swelling had improved. 3 months after stent
      placement the left arm swelling has not recurred.

PMID- 23555494
TI  - Patient with a massive idiopathic thrombosis in the inferior vena cava.
AB  - A 50 year-old man with no significant medical history was admitted for dyspnea
      and left femoral swelling. Contrast-enhanced computed tomography revealed
      pulmonary thromboembolism (PTE) and a thrombus in the inferior vena cava (IVC).
      The thrombus extended from the proximal IVC to the left popliteal vein.
      Therefore, we decided that an IVC filter insertion was difficult to indicate.
      Urgent IVC and peripheral vein thrombectomy was performed under cardiopulmonary
      bypass. On postoperative day 1, venous ultrasonography showed residual deep vein
      thrombosis in the left external iliac-femoral vein and the popliteal vein. The
      IVC filter insertion was performed to prevent the recurrence of PTE.

PMID- 23555495
TI  - Ischemic Colitis Following Transarterial Embolization for Type 2 Endoleak of
      EVAR: Report of a Case.
AB  - A 71 year old man was diagnosed to have enlargement of abdominal aortic aneurysm
      due to type 2 endoleak two years after endovascular aneurysm repair (EVAR). 3D-CT
      demonstrated a type 2 endoleak that originated from the superior mesenteric
      artery that fed the inferior mesenteric artery and the right iliolumbar artery
      that flowed into the 4th lumbar artery. Transarterial embolization was performed
      by means of N-butyl-2-cyanoacrylate (NBCA). After the treatment, he suffered
      ischemic colitis that extended from the sigmoid colon to the descending colon.
      Conservative treatment was mainly performed, and clinical improvement was
      observed over time. He was discharged after 73 postoperative days.

PMID- 23555496
TI  - Late-onset primary intestinal lymphangiectasia successfully managed with
      octreotide: a case report.
AB  - We report a case of a patient with late-onset primary lymphangiectasia whose
      persistent diarrhoea was successfully managed with octreotide. A 63 year-old man
      visited our clinic with a complaint of worsening general edema. Gastrointestinal
      endoscopy revealed typical whitish jejunal villi, which suggested primary
      intestinal lymphangiectasia. Despite a diet, supplemented with medium-chain
      triglycerides; antiplasmin therapy; oral corticosteroids; and surgery, including
      pericardial window and lymphaticovenous anastomoses; his symptoms, including
      watery diarrhoea, showed no improvement. After administration of octreotide, his
      persistent diarrhoea resolved within a couple of days. Octreotide was continued
      for 2 months. Thereafter, his diarrhoea has not recurred for 6 months.

PMID- 23555497
TI  - Hepatic artery pseudoaneurysm with extrahepatic biliary obstruction.
AB  - Hepaticartery pseudoaneurysms are a rare complication of chronic pancreatitis.
      However, giant pseudoaneurysms (80 mm) and complicated biliary obstructions are
      extremely rare. This article reports a 75 year-old man with chronic pancreatitis
      that presented as upper abdominal pain and obstructive jaundice. Computed
      tomography revealed a hepatic artery pseudoaneurysm measuring 80 * 72 * 70 mm. We
      performed aneurysm resection and common hepatic artery bypass, using a great
      saphenous vein graft in the patient. The postoperative course was uneventful, and
      he was discharged on the 10th postoperative day. However, on the 135th
      postoperative day, he died of massive hemorrhage into the peritoneal cavity.

PMID- 23555498
TI  - Endovascular surgery for inflammatory abdominal aortic aneurysm with contrast
      allergy-usefulness of carbon dioxide angiography and intravascular ultrasound: a
      case report.
AB  - We report a patient with inflammatory abdominal aortic aneurysm who underwent
      endovascular aneurysm repair, despite his having an allergy to iodinated contrast
      medium and anatomy unsuitable for the procedure. Intravascular ultrasound-guided
      and CO2-assisted aortic stent graft placement was performed, and the procedures
      resulted in the successful exclusion of the aneurysm with regression of the
      mantle sign and resolution of hydronephrosis.

PMID- 23555500
TI  - Third Asian PAD Workshop.

PMID- 23555499
TI  - Endovascular treatment of ruptured intercostal arteriovenous fistulas associated
      with neurofibromatosis type 1.
AB  - Wereport a rare case of ruptured intercostal arteriovenous fistula in a patient
      with neurofibromatosis type 1. The patient presented with severe back pain.
      Angiography revealed ruptured intercostal arteriovenous fistulas. Successful coil
      embolization to occlude the fistulas and the aneurysm resulted in successful
      recovery of the patient.

PMID- 23555501
TI  - Recent advances in medical treatment for lymphedema.
AB  - As medical treatment for lymphedema, combined physical therapy with guidance
      regarding daily living is recommended. Recently, training has been conducted on a
      nationwide scale, and this therapy has gradually and commonly been employed. This
      therapy consists of daily living guidance to prevent edema deterioration, skin
      care, manual lymph drainage, compression therapy, and exercise therapy. The
      number of hospitals in which all procedures can be adequately performed is
      limited. There is no treatment to completely cure lymphedema. Patients' self-care
      based on the contents of treatment is essential for relieving symptoms. (English
      Translation of J Jpn Col Angiol 2008; 48: 167-172.).

PMID- 23555502
TI  - Recent developments in morphology of lymphatic vessels and lymph nodes.
AB  - This paper reviews the morphology of lymphatics and lymphangiogenesis in vivo,
      microenvironments that promote lymphangiogenesis, and the structure and function
      of lymph nodes. Lymphatic capillaries consist of a single layer of lymphatic
      endothelial cells (LECs) and have valves, while collecting lymphatics are endowed
      with smooth muscle cells (SMCs) and valves besides a single layer of LECs. In the
      embryonic rat diaphragm, LECs first migrate presumably according to interstitial
      fluid flow and later join to form lymphatic vessels. SMCs of the collecting
      lymphatics are apparently differentiated from mesenchymal cells. LECs cultured on
      Cell Culture Inserts under a low oxygen condition proliferate very well and form
      a lymphatic network. LECs cultured on a collagen fiber network with a natural
      three-dimensional (3D) architecture under low oxygen rapidly form a 3D lymphatic
      network. The lymph node initiates an immune response as a critical crossroads for
      the encounter between antigen-presenting cells, antigens from lymph, and
      lymphocytes recruited into nodes from the blood. The node consists of spaces
      lined with LECs and parenchyma. High endothelial venules in the node strongly
      express Aquaporin-1, suggesting their involvement in the net absorption of water
      from lymph coming through afferent lymphatics. SMCs in node capsules seem to be
      involved in squeezing out lymphocytes and lymph. (English Translation of J Jpn
      Col Angiol 2008; 48: 107-112.).

PMID- 23555503
TI  - Diabetes-related lower extremities amputations in saudi arabia: the magnitude of
      the problem.
AB  - BACKGROUND: Data on diabetes-related lower extremities amputations in the Kingdom
      of Saudi Arabia (KSA) and perhaps in all of Middle East and North African (MENA)
      countries are limited, in view of the absence of national registries. METHODS:
      This review aims to challenge media figures by review of data in the local
      database of the author, available published data, as well as by analysis of
      recent annual reports of the Saudi Ministry of Health to estimate the magnitude
      of the problem. Different methods of analysis are used based on the number of
      beds, operations and admissions in KSA to generate approximate figures of the
      annual expected numbers of amputations in KSA and MENA countries. The 2010
      International Diabetes Federation IDF comparative prevalence rate of 16.8% was
      used to standardize the analysis methods. RESULTS: Findings of 2 previous studies
      and 3 analytical methods led me to the prediction that about 325 amputations are
      likely to occur annually in Jeddah compared to 741 in Riyadh and 3970 in KSA.
      When we applied the results of KSA to those of MENA countries, 44208 amputations
      were predicted annually. CONCLUSION: Half a million diabetes-related amputations
      of the lower extremities are likely to occur in KSA and MENA countries over the
      coming decade. National registries are urgently needed.

PMID- 23555504
TI  - Surgical procedures for renal artery aneurysms.
AB  - OBJECTIVE: The aim of this study was to assess the strategy and surgical
      procedures for treating a renal artery aneurysm (RAA). PATIENTS AND METHODS: We
      retrospectively reviewed the surgical strategy for 21 cases with RAA between 2001
      and 2010 at this institution. Treatment was indicated for patients with an RAA
      larger than 2 cm and/or symptoms. Surgical treatment was the initial strategy,
      and coil embolization was indicated in the case of narrow-necked, saccular,
      extraparenchymal aneurysms. RESULTS: Fifteen patients in 21 cases received an
      aneurysmectomy and renal artery reconstruction with an in-situ repair. One
      patient underwent an unplanned nephrectomy, and coil embolization was performed
      in 5 patients. CONCLUSION: In-situ repair was safe and minimally invasive. RAA,
      even in the second bifurcation, could be exposed by a subcostal incision, and the
      transperitoneal approach permitted the safe treatment of an RAA with acceptable
      results, in our simple preservation of renal function.

PMID- 23555505
TI  - Non-Contrast Renal MR Angiography: Value of Subtraction of Tagging and Non
      Tagging Technique.
AB  - PURPOSE: The aim of this study was to examine the usefulness of the subtraction
      technique of non-contrast renal magnetic resonance angiography (MRA) between
      tagged and non-tagged data collection. MATERIAL AND METHODS: We performed renal
      MRA on eleven healthy volunteers using a 3T MRI unit. For renal MRA, a three
      dimensional balanced type steady-state free precession (SSFP) sequence (True
      FISP, Siemens) was used with diaphragmatic navigator gating. We tried to acquire
      selective arterial images by subtracting black-blood images (tagged images, on
      which arterial longitudinal magnetization was nearly zero by selective inversion
      of upper-stream aortic flow) from bright-blood images (non-tagged images, on
      which arterial flow is bright due to inflow effect). For analysis, two
      radiologists independently evaluated the visual quality of the axial and coronal
      targeted maximum intensity projection images (MIP) of original bright-blood MRA
      and subtraction MRA. RESULTS: Visualization of the main stem of the renal
      arteries and their 1st branches were satisfactory on both techniques, and there
      was no statistically significant difference. The score of 2nd branch appeared
      superior with the subtraction method, but only the right side showed a
      statistically significant difference (P <0.01). Visualization of small
      intraparenchymal arteries was significantly superior with subtraction method on
      both sides. CONCLUSION: We tried to improve selective demonstration of renal
      arterial branches using subtraction technique. Although full sequence
      optimization was not performed, this pilot study showed this technique to be
      slightly time-consuming but superior in visualization of peripheral branches and
      possibly more sensitive in detecting small vessel abnormalities.

PMID- 23555506
TI  - Clinical Results of Endovascular Abdominal Aortic Aneurysm Repair in Patients
      with Renal Insufficiency without Hemodialysis.
AB  - OBJECTIVE: Chronic renal insufficiency may be a relative contraindication to
      endovascular aneurysm repair (EVAR) for the use of contrast enhanced mediums. It
      is thought that more contrast enhanced media are needed in patients who are not
      anatomically suitable for EVAR, because of procedural difficulties. We reviewed a
      2 year EVAR experience at our institution to determine whether the procedure and
      use of contrast enhanced mediums has any deleterious effect on renal function in
      patients with pre-existing chronic renal insufficiency. MATERIALS AND METHODS:
      EVAR was performed in 46 patients with pre-existing chronic renal insufficiency
      without hemodialysis. Patients were retrospectively assigned to two groups on the
      basis of their preoperative creatinine clearance levels. Furthermore, patients
      were assigned to two other groups on the basis of anatomical suitability for
      EVAR. The absolute change in the serum creatinine (Cr) level was reviewed in the
      each renal insufficiency group between the preoperative and post-operative time
      periods. RESULTS: No increase in the serum Cr level was noted, and no patient
      required temporary or permanent hemodialysis, in any of the groups. CONCLUSIONS:
      EVAR with contrast agents can be accomplished in patients with chronic renal
      insufficiency without hemodialysis; therefore,elevated Cr levels maynot be a
      contraindication in EVAR.

PMID- 23555507
TI  - Early outcomes of open abdominal repair versus endovascular repair for abdominal
      aortic aneurysm: report from national hospital organization network study in
      Japan.
AB  - OBJECTIVE: Early outcomes of open abdominal repair (OS) versus endovascular
      repair (EVAR) for abdominal aortic aneurysm were retrospectively analyzed, after
      commercialized devices for EVAR had become available in Japan. PATIENTS AND
      METHODS: A total of 781 consecutive patients (OS, n = 522; EVAR, n = 259) were
      treated at ten medical centers between January 2008 and September 2010. The OS
      group comprised patients with preoperative shock (SOS, n = 34) and without shock
      (NOS, n = 488). RESULTS: Patients in the EVAR group were 3 years older than those
      in the NOS group. There was greater prevalence of hostile abdomen, on dialysis,
      chronic obstructive pulmonary disease on inhaled drug, and cerebrovascular
      disease in the EVAR group than in the NOS group. Surgical mortality was 16 cases
      (2.0% in all patients, EVAR: 0.8%, NOS: 1.4%, SOS: 21%). Hospital stay >30 days
      was documented in 52 (11%) with NOS, 11 (33%) with SOS, and 8 (3%) with EVAR.
      Thirty late deaths included 6 aneurysm related death and 14 cardiovascular causes
      at a mean follow up of 1.0 year. The survival rates freedom from all cause death
      at one year, were 95 +/- 1% in NOS and 94 +/- 2% in EVAR respectively.
      CONCLUSION: Though significant differences in patient characteristics among three
      groups were noted, early results were satisfactory.

PMID- 23555508
TI  - Lowered LDL-C Levels Reduce Later Local Vascular Events after Surgical or
      Endovascular Treatment of Peripheral Artery Disease.
AB  - PURPOSE: To examine the relationship between incidence of later, local vascular
      events (restenosis and occlusion) and clinical factors including lipid levels
      after surgical or endovascular treatment of peripheral artery disease (PAD).
      METHODS: Consecutive 418 PAD lesions (in 308 patients under the age of 70)
      treated with surgical (n = 188) or endovascular (n = 230) repair for iliac (n =
      228) and infrainguinal (n = 190) lesions were retrospectively analyzed. Clinical
      features and lipid levels were compared between patients who developed vascular
      events (n = 51; VE group) and those who did not (n = 257; NoVE group). RESULTS:
      Among assessed factors, post-therapeutic low-density lipoprotein cholesterol (LDL
      C) levels (mg/dL) were significantly higher in the VE group (120.4 +/- 31.2) than
      in the NoVE group (108.2 +/- 25.1) (P = 0.01). Infrainguinal lesions were more
      common in the VE than in the NoVE group (P <0.001). Cox hazard analysis indicated
      that infrainguinal lesions relative to iliac lesions significantly increased the
      risk of vascular events (hazard ratio (HR) 3.35; 95% CI 1.63-6.90; P = 0.001) and
      post-therapeutic LDL-C levels <130 (mg/dL) decreased the risk (HR 0.34; 95%CI
      0.17-0.67; P = 0.002). CONCLUSION: Lowered post-therapeutic LDL-C levels can
      decrease the risk of later, local vascular events after PAD treatment. These
      results may support the rationale for aggressive lipid-modifying therapy for PAD.

PMID- 23555509
TI  - Adventitial cystic disease of the popliteal artery.
AB  - We describe a patient with adventitial cystic disease of the popliteal artery
      with intermittent claudication involving the right calf during exercise. Magnetic
      resonance imaging (MRI) and computed tomography (CT) revealed a cystic lesion
      that encircled and compressed the popliteal artery. Resection of the cyst
      involving a segment of the affected popliteal artery and interposing an
      autologous vein graft resolved the symptoms, and the postoperative course was
      uneventful. The cyst was histologically similar to a ganglion.

PMID- 23555510
TI  - Surgical reconstruction for intrathoracic aneurysm originating from proximal part
      of the right subclavian artery.
AB  - Subclavian artery aneurysms are comparatively rare in peripheral aneurysms. We
      experienced a case of intrathoracic aneurysm originating from the proximal part
      of the right subclavian artery. A 78 year-old man was referred to our hospital
      with the diagnosis of a right subclavian artery aneurysm. Enhanced computed
      tomography demonstrated an intrathoracic aneurysm, originating from the right
      subclavian artery just proximal of its origin. Through a median sternotomy and
      supra-infraclavicular incision, we reconstructed the brachiocephalic and right
      common carotid arteries and bypassed to the distal part of the right subclavian
      artery by using a T-shaped vascular graft and the aneurysm was excluded.

PMID- 23555511
TI  - Sural Artery Bypass in Buerger's Disease: Report of a Case.
AB  - A 72 year-old man was admitted to the hospital to receive treatment for resting
      pain and an ulcer, which had developed on an amputation stump, 4 months after he
      had undergone a thrombectomy, below-the-knee popliteal-dorsal pedis artery bypass
      of his left leg, and digital amputation of his 2nd toe. Angiography demonstrated
      diffuse arterial and bypass occlusion in his left leg that did not include a
      sural artery, which was the main collateral. Therefore, the patient underwent
      reversed saphenous vein bypass from the common femoral artery to the medial sural
      artery. His leg pain disappeared, and the ulcer healed promptly.

PMID- 23555512
TI  - A case report of aneuysmectomy after thrombo-intimectomy for spontaneous isolated
      superior mesenteric artery dissection.
AB  - A 53 year-old man was admitted with acute onset of severe abdominal pain, and we
      performed emergent thrombectomy and intimectomy for acute, complete occlusion of
      superior mesenteric artery (SMA) due to its spontaneous dissection. However, 4
      months later the operated part of the SMA enlarged due to aneurysm and the
      patient was treated by aneuysmectomy and iliac-mesenteric bypass using a
      saphenous vein. Aggressive treatment such as surgical or endovascular procedure
      is necessary for severe ischemia due to SMA dissection.

PMID- 23555513
TI  - Mycotic Celiac Artery Aneurysm Following Infective Endocarditis: Successful
      Treatment Using N-butyl Cyanoacrylate with Embolization Coils.
AB  - Mycotic celiac artery aneurysm following infective endocarditis is extremely rare
      and, to our knowledge, only four cases have been reported in the literature to
      date. We describe the case of a 60 year-old man who developed a mycotic aneurysm
      of the celiac artery, which was detected by computed tomography (CT) following an
      episode of infective endocarditis. He successfully underwent endovascular
      isolation and packing of the aneurysm using N-butyl cyanoacrylate (NBCA) with
      embolization coils.

PMID- 23555514
TI  - Congenital systemic-pulmonary collateral vein unexpectedly noticed after central
      venous catheter insertion.
AB  - Congenital systemic-pulmonary collateral vein (i.e. levoatriocardinal vein) is an
      uncommon cardiac anomaly. We report a rare case of congenital systemic-pulmonary
      collateral vein incidentally noticed after accidental migration of a central
      venous catheter. Cardiac CT showed the vertical vein connected to the left upper
      pulmonary vein (LUPV) and another thin abnormal vessel was shown running caudally
      from the LUPV, connecting to the coronary sinus. Furthermore, the normal
      connection between the LUPV and the left atrium remained. There were two
      levoatriocardinal veins from the LUPV without atrial egress failure. To our
      knowledge, this might be the first report of such a case.

PMID- 23555515
TI  - Endovascular management of may-thurner syndrome.
AB  - May-Thurner syndrome or iliac vein compression syndrome is associated with deep
      vein thrombosis (DVT) resulting from chronic compression of the left iliac vein
      against lumbar vertebrae by the overlying right common iliac artery.
      Historically, May-Thurner syndrome has been treated with anticoagulation therapy.
      However, this therapy can be problematic when given alone, because it prevents
      the propagation of the thrombus without eliminating the existing clot.
      Furthermore, it does not treat the underlying mechanical compression.
      Consequently, syndrome who was managed by anticoagulation therapy alone, there is
      a significant chance that the patient will develop recurrent deep vein thrombosis
      or post thrombotic syndrome or both. Recently, both retrospective and prospective
      studies have suggested that endovascular management should be front-line
      treatment; endovascular management actively treats both the mechanical
      compression with stent placement and the thrombus burden with chemical
      dissolution. We report our case of 53 years old male patient with May Thurner
      syndrome who managed by endovascular treatment.

PMID- 23555516
TI  - Huge hemangioma in the chest mimicking a breast tumor: report of a case.
AB  - A 35 year-old man first noticed an elastic mass like breast tumor in his left
      chest 17 years ago. It enlarged to the size of a child's head. Computed
      tomography showed a well-circumscribed mass in the left chest. Lumpectomy was
      performed. The mass was located under the thin major pectoralis muscle, covered
      with a white fibrous capsule. The specimen weighed 1360 g and measured 18 * 14 *
      8 cm. Histological examination revealed a cavernous hemangioma. To the best of
      our knowledge, this is the first reported case of a chest hemangioma arising from
      connective tissue and located under the major pectoralis muscle.

PMID- 23555517
TI  - Staged hybrid debranching and thoracic endovascular aneurysm repair for multiple
      aortic aneurysms after conventional open repair of the descending aorta: a case
      report.
AB  - Endovascular repairs of thoracic and thoracoabdominal aortic aneurysm have
      recently been proposed as a less invasive alternative to conventional open
      surgical repair. In selective cases, adjunctive bypass surgery may be required to
      provide an adequate landing zone. We describe a case of staged hybrid debranching
      and thoracic endovascular aneurysm repair for distal aortic arch and
      thoracoabdominal aortic aneurysms after conventional open repair of the
      descending aorta.

PMID- 23555518
TI  - A Case of Embolism due to a Floating Thrombus Migrating from the Left Atrial
      Appendage to the Ostium of the Celiac Artery.
AB  - The present case was a 70 year-old dialysis patient who had experienced a prior
      cerebral infarction following atrial fibrillation. Her shunt suddenly occluded
      during dialysis, and she was transferred to our hospital. Transesophageal
      echocardiography revealed a floating, ball-like thrombus in the left atrial
      appendage (LAA). After thrombectomy in the shunt, acute thrombi were extracted.
      Despite anticoagulant therapy, the ball-like thrombus in the LAA did not
      dissipate and instead continued to enlarge. We planned surgical intervention
      involving a left atrial appendectomy without cardiopulmonary bypass through a
      left thoracotomy. However, her thrombus disappeared out of the LAA when she was
      intubated in the operating room. Her surgery was, therefore, stopped, and
      extubation was carried out. A computed tomography (CT) scan showed that the
      embolism had moved to the ostium of the celiac artery. Incidentally, this celiac
      artery had already been obstructed, and her inferior mesenteric artery had been
      the main supply of blood flow to the intestine, explaining why she had not
      developed intestinal ischemia. We continued anticoagulant therapy with warfarin.
      Follow-up CT studies were conducted at the outpatient clinic. However, the
      patient died due to a wide cerebral infarction before the 6-month checkup.

PMID- 23555521
TI  - The establishment of new lympholgy: overview.

PMID- 23555519
TI  - Femoral vein compression resulting from a ganglion of the hip joint: a case
      report.
AB  - The development of a ganglion in the hip joint is a rare cause of lower limb
      swelling. We herein describe a case of a ganglion of the hip with compression of
      the femoral vein that produced signs and symptoms that mimicked a deep vein
      thrombosis. Needle aspiration of the ganglion was easily performed, and swelling
      of the left lower limb promptly improved. Intensive follow-up of this case was
      important because the recurrence rate of ganglions after needle aspiration is
      high.

PMID- 23555522
TI  - Sentinel node and mechanism of lymphatic metastasis.
AB  - The validity and clinical usefulness of the sentinel node (SN) concept for breast
      cancer has been confirmed, and individualized limited surgery based on diagnosis
      of SN metastasis is presently performed. In the future, SN navigation surgery
      (SNNS) will be actively applied to the treatment of early gastric cancer, and an
      intraoperative real-time reverse transcription-polymerase chain reaction (RT-PCR)
      assay to detect SN micrometastasis of gastric cancer is under development. Not
      only anatomical factors, but also many other factors such as local
      immunosuppression in the SN and lymphoangiogenesis may be involved in development
      of SN micrometastasis, and clarification of the mechanisms of metastasis and
      development of treatment methods are awaited. (*English Translation of J Jpn Col
      Angiol 2008; 48: 137-142.).

PMID- 23555523
TI  - Recent advance in lymph dynamic analysis in lymphatics and lymph nodes.
AB  - Lymphatics are a unidirectional transport system that carries fluid from the
      interstitial space and back into the blood stream. Initial lymphatics take up not
      only fluid but also high-molecular-weight substances, such as plasma proteins and
      hyaluronan; immune cells, such as lymphocytes, macrophages, and dendritic cells;
      and colloidal particles, such as carbon particles, bacteria, and tattoo dye.
      Interstitially injected colloidal particles are known to accumulate in the
      regional lymph nodes. This phenomenon is applied to find sentinel lymph nodes in
      cancer patients. Lymph flow rate and composition are influenced by interstitial
      fluid, lymphatic pump activity, and intra-lymphatic pressure. Lymph composition
      is changed during its flow downstream. In this review, the main focus is on the
      mechanisms of lymph formation at the initial lymphatics and lymph transport
      through the collecting lymphatics and lymph nodes. (*English Translation of J Jpn
      Coll Angiol, 2008, 48: 113-123.).

PMID- 23555524
TI  - Current topics of immunohistochemical and biological properties of human
      lymphatic endothelial cells.
AB  - We examined the immunohistochemical properties of selective lymph vessel markers
      such as LYVE-1, podoplanin, Prox-1, and VEGF R3, as well as NO synthase (NOS) and
      cyclo-oxygenase (COX) in two kinds of human lymphatic endothelial cell isolated
      from collecting and initial lymph vessels. The constitutively expressed genes in
      the two kinds of lymphatic endothelial cell were also evaluated using
      oligonucleotide microarray analysis and RT-PCR. We also investigated the effects
      of the oxygen concentration in culture conditions on the proliferative activities
      of the two kinds of human lymphatic endothelial cell. Immunoreactivity to LYVE-1
      and the RT-PCR expression level of LYVE-1 mRNA in endothelial cells of initial
      lymph vessels were stronger than those of collecting lymph vessels.
      Immunoreactivity to ecNOS, iNOS, COX1, and COX2 was also found to be
      significantly higher than in collecting lymph vessels. In contrast, an increase
      in the O2 concentration ranging from 5% to 21% caused a significant reduction in
      the proliferative activity of endothelial cells in collecting lymph vessels. In
      conclusion, these findings suggest that there exists a marked heterogeneity in
      the immunohistochemical, genomic, and proliferative activity of human lymphatic
      endothelial cells between initial and collecting lymph vessels. (*English
      Translation of J Jpn Coll Angiol, 2008, 48: 125-130.).

PMID- 23555525
TI  - Mucosal immunity in gut and lymphoid cell trafficking.
AB  - Intestine has a well-developed lymphatic system that is closely related with its
      functions, such as mucosal immunological defense or absorption of nutrients.
      Intestinal lymphoid cells such as lymphocytes, macrophages/monocytes, or
      dendritic cells are continuously migrating through intestinal mucosa, thereby
      facilitating their immune responses. Their migrations are well controlled by well
      organized molecular mechanisms including adhesion molecules, chemokines, etc.
      This manuscript will review how dysfunction of lymphoid cell migration is
      involved in intestinal inflammation, especially in the pathophysiology of
      intestinal bowel diseases. (*English Translation of J Jpn Coll Angiol 2008; 48:
      143-149.).

PMID- 23555526
TI  - Cutaneous polyarteritis nodosa: an update.
AB  - Cutaneous symptoms are observed in 25%-60% of polyarteritis nodosa (PN) patients.
      On the other hand, cutaneous polyarteritis nodosa (CPN) is designated for the
      cutaneous limited form of PN and demonstrates benign prognosis. However, there
      has been much debate on whether or not CPN can progress to PN. Although CPN
      lesions are fundamentally limited to skin, some CPN cases show extracutaneous
      symptoms such as peripheral neuropathy and myalgia. According to PN diagnostic
      criteria, a disease with both cutaneous and at least one extracutaneous symptom
      with appropriate histopathological findings can be diagnosed as PN. The same is
      true according to diagnostic criteria established by American College of
      Rheumatology (ACR). In addition, there are no specific diagnostic criteria for
      CPN. In this study, CPN cases were retrospectively collected from multiple
      Japanese clinics, and analyzed for detailed clinical and histopathological
      manifestations, in order to redefine the clinical entity of CPN and to propose
      appropriate diagnostic criteria for CPN and PN. According to the CPN description
      in Rook's Textbook of Dermatology, one of global standard textbooks, we collected
      22 cases with appropriate histopathological findings. Of the 22 cases, none
      progressed to PN or death during the follow-up period, 32% had peripheral
      neuropathy, and 27% had myalgia. Regarding extracutaneous symptoms with CPN, 17
      dermatological specialists in vasculitis sustained the opinion that CPN can be
      accompanied by peripheral neuropathy and myalgia, but these symptoms are limited
      to the same area as skin lesions. Based on these results, we devised new drafts
      for CPN and PN diagnostic criteria. Our study shows the efficacy of these
      criteria, and most dermatologists recognized that our new diagnostic criteria for
      CPN and PN are appropriate at the present time. In conclusion, this study
      suggests that CPN does not progress to PN, and introduces new drafts for CPN and
      PN diagnostic criteria. (*English Translation of J Jpn Coll Angiol 2009; 49: 87
      91.).

PMID- 23555527
TI  - Genetics of microscopic polyangiitis in the Japanese population.
AB  - The epidemiology of ANCA-associated vasculitis is substantially different between
      Caucasians and Japanese, which may be related to differences in genetic
      backgrounds. In this review, I discussed our findings on the genetics of
      microscopic polyangiitis (MPA) in Japanese. Analysis of HLA genes revealed a
      significant increase in the HLA-DRB1*09:01-DQB1*03:03 haplotype MPA. This is one
      of the most frequent haplotypes in Japanese, but is nearly absent in Caucasians,
      and has been shown to be associated with multiple autoimmune diseases. Analysis
      of KIR genes revealed significant decreases in the carrier frequency of an
      activating receptor KIR2DS3 in MPA. When KIRs were analyzed in combination with
      HLA ligands, the proportion of individuals carrying KIR3DL1 and HLA-Bw4 but not
      KIR3DS1, the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was
      significantly increased in MPA. These results suggested that decreased activation
      of NK and/or T cells may cause a predisposition to MPA. LILRA2 is an activating
      receptor involved in granulocyte and macrophage activation. LILRA2 SNP rs2241524
      G >A, which disrupts the intron 6 splice acceptor site, was significantly
      associated with MPA. The risk allele produces an LILRA2 isoform lacking three
      amino acids in the linker region. These findings, when confirmed by larger-scale
      studies, will shed light on the molecular mechanisms of MPA. (*English
      Translation of J Jpn Coll Angiol 2009; 49: 31-37.).

PMID- 23555528
TI  - Pathogenesis of Vasculitis in env-pX Rats.
AB  - Transgenic rats carrying the env-pX gene of human T-cell leukemia virus type I
      (env-pX rats) develop necrotizing angiitis resembling human polyarteritis nodosa
      (PN). In the development of vasculitis in these rats, the thymus plays an
      important role. In this review, we provide an outline of the pathogenesis of
      vasculitis observed in env-pX rats, and discuss the developmental mechanism of
      human necrotizing angiitis such as PN with an unknown cause. (*English
      Translation of J Jpn Coll Angiol 2009; 49: 17-20.).

PMID- 23555529
TI  - Are There Any Objections against Our Hypothesis That Buerger Disease Is an
      Infectious Disease?
AB  - In 1878, Winiwarter used a microscope and reported a case of 57 year-old man
      demonstrating Buerger disease. After that, 134 years passed. Leo Buerger and
      Edgar V. Allen strongly suggested that Buerger disease is an infectious disease
      without any doubt. Also, an etiologic point is the luminal infectious thrombus,
      which is thought to be the core of the disease. Many etiological factors were
      proposed and then discarded after academic scrutiny, but two big discoveries were
      made in 2005 and 2008. Namely, periodontal bacteria DNA was found in the occluded
      arteries of 93% of patients with Buerger disease, and periodontal bacteria
      (typical weak bacteria) were found to dwell in the platelets. Using these
      evidences, supported by genetic and epidemiological facts, we could almost
      explain the pathogenesis or clinical course of Buerger disease, which had been
      already studied.

PMID- 23555531
TI  - Relation between Isolated Venous Thrombi in Soleal Muscle and Positive Anti
      Nuclear Antibody.
AB  - OBJECTIVE: In patients with isolated soleal vein thrombosis (SVT), the relation
      between acute thrombi and positive anti-nuclear antibody (ANA) was investigated.
      SUBJECTS AND METHODS: The subjects were 116 lower extremities in 86 patients with
      SVT. They were diagnosed and examined by ultrasonography and blood serum analysis
      (D-dimer, ANA), and had been followed up every three months. RESULTS: They had
      acute SVT in 35 limbs (30%) and chronic SVT in 86 limbs (70%), and they had
      positive ANA in 63%. They had recurrent SVT in 26%, and all were positive for
      ANA. CONCLUSION: ANA-positivity might be a risk factor for acute thrombi in
      patients with SVT. (*English Translation of J Jpn Coll Angiol 2010; 50: 417
      422.).

PMID- 23555532
TI  - Deep vein thrombosis in orthopedic surgery of the lower extremities.
AB  - To prevent pulmonary embolism due to deep venous thrombosis (DVT), we have
      treated 611 patients undergoing orthopedic surgery of the lower extremities with
      our protocol including pre- and postoperative ultrasonic venous screening and
      anticoagulant therapy if necessary. A total of 118 patients (19.3%) developed
      DVT. Among demographic and clinical factors, the site of operation (knee joint
      surgery: odds ratio 5.17), age (>60: odds ratio 3.91), and operation time (>120
      minutes: odds ratio 4.52) were identified as significant risk factors of
      development of DVT. One patient received an infusion of urokinase for DVT of
      femoral vein, but no patients developed serious postoperative bleeding or
      pulmonary thromboembolisms. (*English Translation of J Jpn Coll Angiol, 2010, 50:
      95-100.).

PMID- 23555530
TI  - Acute type a aortic dissection: for further improvement of outcomes.
AB  - Despite improved outcomes of acute type A aortic dissection (AAAD), many patients
      die at the moment of onset, and hospital mortality is still high. This article
      reviews the latest literature to seek the best possible way to optimize outcomes.
      Delayed diagnosis is caused by variation in or absence of typical symptoms,
      especially in patients with neurological symptoms. Misdiagnosis as acute
      myocardial infarction is another problem. Improved awareness by physicians is
      needed. On arrival, quick admission to the OR is desirable, followed by
      assessment with transesophageal echocardiography, and malperfusion already exists
      or newly develops in the OR; thus, timely diagnosis without delay with
      multimodality assessment is important. Although endovascular therapy is
      promising, careful introduction is mandatory so as not to cause complications.
      While various routes are used for the systemic perfusion, not a single route is
      perfect, and careful monitoring is essential. Surgical treatment on octogenarians
      is increasingly performed and produces better outcomes than conservative therapy.
      Complications are not rare, and consent from the family is essential. Prevention
      of AAAD is another important issue because more patients die at its onset than in
      the following treatment. In addition to hereditary diseases, including bicuspid
      aortic valve disease, the management of blood pressure is important.

PMID- 23555533
TI  - Management of the infected aortoiliac aneurysms.
AB  - PURPOSE: We have reviewed ruptured and nonruptured infected aortoiliac aneurysms
      to study the clinical presentation, management and eventual outcome of patients
      managed with in situ prostheses, axillofemoral prostheses grafts and endovascular
      reconstruction. DESIGN: A retrospective chart review of 16 cases treated at a
      single institution. METHODS: From January 2007 to March 2008, a total of 93
      patients with aortoiliac aneurysms underwent surgical repair at our institution.
      Among these, 16 patients (17.2%) were shown to be infected aneurysms of the
      infrarenal (n = 6), juxtarenal (n = 2), and pararenal aorta (n = 1); the others
      were 5 common, 1 external, and 1 internal iliac arteries. Fourteen patients were
      male and 2 were female with the mean age of 66 years (range, 45-79). In all
      cases, the diagnosis was confirmed by abdominal computed tomography and empirical
      parenteral antibiotics were administered at least 1 week, unless in patients need
      emergency operations. At the time of an operation, all were saccular and were
      classified as primary infected aortoiliac aneurysms. Thirteen patients had
      surgical debridement with in situ graft interposition and omental wrapping, 2
      underwent aneurysm exclusion and extra-anatomic (axillo-femoral) bypass, 1
      underwent aneurysmectomy of left external iliac artery and
      polytetrafluoroethylene (PTFE) graft interposition, and 1 underwent endovascular
      exclusion. The parenteral antibiotics were continued in the postoperative period
      for 4-6 weeks. Chronic renal disease was present in 37.5% (6/16), with diabetes
      mellitus present in 31.25% (5/16). The most common pathogen was Salmonella sp. (n
      = 6) and E. coli (n = 5). Thirty-seven percent (6/16) of the patients presented
      late, with a 37.5% (6/16) incidence of ruptured (4 contained, 2 free ruptured)
      that needed emergency surgery. RESULTS: Disease-specific mortality was 31.25%
      (5/16). The 30-day mortality rate of ruptured cases is high 67% (4/6), because
      patients present late in the course of the disease. One patient who underwent
      aneurysm exclusion and extra-anatomic (axillo-femoral) bypass died 6 months later
      from burst aortic stump. Salmonella and E. coli are the most common pathogens.
      CONCLUSIONS: Early diagnosis followed by surgical intervention with proper
      antibiotic coverage provides the best results. Mortality rate was still high in
      patients with sepsis and rupture. An in situ graft interposition and omental
      wrapping is a safe option for revascularization of infected aneurysms of the
      iliac arteries and infrarenal aorta.

PMID- 23555534
TI  - Interface pressures derived from oversize compression stockings.
AB  - OBJECTIVES: To clarify interface pressures (IP) derived from class II and III
      oversize stockings. METHODS: Healthy volunteers with legs fitting size S (n =
      10), M (n = 6), or L (n = 6) stockings wore class II and III stockings of various
      sizes up to 5L. IPs were measured in the supine and the standing position with
      each stocking on. RESULTS: In the subjects with size S legs, the IPs in the
      standing position while wearing S and M class III stockings were 43.5 +/- 4.7 and
      40.4 +/- 5.4 mmHg respectively. These IPs were significantly higher than the IP
      while wearing the S size class II stocking (33.3 +/- 5.9 mmHg). IPs derived from
      L, LL, 3L, 4L, 5L class III stockings were not significantly different from IP
      with the S size class II stocking. The results were similar for the subjects with
      size M legs while wearing the size M and L class III stockings and for the
      subjects with size L legs while wearing the size L and LL class III stockings vs.
      the appropriate size class II stocking. CONCLUSION: Based on these findings, a
      larger size class III stocking can provide similar or even higher IPs compared to
      an appropriate size class II stocking.

PMID- 23555535
TI  - Elastic multilayer bandages for chronic venous insufficiency: features of our
      technique.
AB  - OBJECTIVES: To evaluate the interface pressure (IP) and stiffness of our elastic
      multilayer bandages (eMLB). METHODS: Three medical staff wrapped the legs of 10
      healthy volunteers with one to six rolls of elastic bandages. The IP was measured
      at the medial aspect of the lower leg at the level of transposition of the medial
      gastrocnemius muscle into the Achilles tendon (level of B1) with the patient
      supine and then standing, for each number of bandages worn. The static stiffness
      index (SSI) was calculated as a difference between these IPs. RESULTS: The IPs in
      the standing position increased linearly for up to five bandages (21.8 +/- 7.2,
      32.5 +/- 6.1, 41.8 +/- 8.5, 52.0 +/- 10.4, 60.3 +/- 11.8, and 66.7 +/- 13.4 mmHg,
      with one to six bandages). SSI also increased linearly for up to five bandages
      (6.8 +/- 5.1, 10.2 +/- 4.8, 13.4 +/- 7.2, 17.4 +/- 8.8, 19.7 +/- 9.1, and 20.4 +/
      9.4 mmHg, with one to six bandages). No significant technical variation in the
      IP was observed among the three operators. CONCLUSIONS: Our eMLB provided stable,
      predictable and sufficient IPs and SSIs in healthy volunteers.

PMID- 23555536
TI  - Evaluation of ITA Graft Function Using CT Angiography.
AB  - OBJECTIVE: A less invasive method to assess internal thoracic artery (ITA) graft
      function after coronary artery bypass grafting (CABG) is desired. This study
      reports the novel method to estimate ITA graft function using CT angiography.
      MATERIALS AND METHODS: Fifty ITA grafts were assessed. Hounsfield Unit transition
      of each graft on the same cross section was detected during the Test Bolus
      Injection, which led to the making of a time density curve (TDC), for each ITA.
      Variables from the TDC were compared statistically with data obtained from Pulse
      Doppler Echo (PDE), the best indicator of graft function, of ITA grafts. RESULTS:
      The ascending slope of the TDC was significantly associated with the following
      PDE data: Velocity time integral (VTI), VTI * Heart Rate (HR) and Mean Flow of
      ITA graft. A multivariate analysis showed an especially strong relationship with
      the ascending slope of the TDC and VTI * HR (R(2) = 0.588). CONCLUSION: The
      ascending slope of the TDC means the concentration transition of contrast media,
      which may be affected by the blood stream in the ITA graft. This study suggests
      the possibility of the ability to assess ITA graft function by CT angiography.

PMID- 23555537
TI  - Subfascial endoscopic perforator surgery using screw-type ports is a very useful
      component of a comprehensive treatment program for chronic venous insufficiency.
AB  - BACKGROUND: Subfascial endoscopic perforator surgery (SEPS) with a two-port
      system utilizing screw-type ports, CO2 insufflation and an ultrasonic coagulation
      system, is a useful procedure that does not require burdensome apparatus and
      techniques. SEPS was accepted as a national advanced medical system by the
      Japanese Ministry of Health, Labor and Welfare in May 2009. PATIENTS AND METHODS:
      Forty-one limbs of 35 patients with 10 active ulcers (C6) and 2 healed ulcers
      (C5) were treated by SEPS between February 2010 and December 2011. Thirty-three
      limbs had concomitant superficial vein surgery. SEPS alone was performed on 8
      limbs, in 6 of which the superficial veins had already been ablated. In 2 limbs,
      incompetent perforating veins (IPVs) existed under the affected skin, around the
      scars of past surgery. RESULTS: All stasis ulcers of the 10 C6 limbs healed
      between 1 week and 14 months after SEPS (mean 2.9 months), with no ulcer
      recurrence during the follow-up period (2 to 24 months). IPVs under the scars
      were easily and safely interrupted by SEPS. CONCLUSION: SEPS is a very useful
      component of a comprehensive treatment program for chronic venous insufficiency,
      especially in patients with venous stasis ulcers and IPVs under the scars of past
      surgery.

PMID- 23555538
TI  - Clopidogrel for Atherothrombotic Event Management in Patients with Peripheral
      Arterial Disease (COOPER) Study: Safety and Efficacy of Clopidogrel versus
      Ticlopidine in Japanese Patients.
AB  - BACKGROUND: Peripheral arterial disease (PAD) has been recognized as an
      independent risk factor for vascular events and contributes to an adverse
      prognosis. Long-term administration of clopidogrel is recommended to prevent
      atherothrombotic events for patients with established PAD. We investigated the
      benefits of clopidogrel treatment in Japanese patients with PAD. MATERIALS AND
      METHODS: COOPER (Clopidogrel for atherOthrombOtic event management in patients
      with PERipheral arterial disease) was a multicenter, randomized, double-blind
      study to evaluate the safety and efficacy of clopidogrel (75 mg/day) compared to
      ticlopidine (200 mg/day) in Japanese patients with PAD. The primary endpoint was
      the cumulative incidence of "safety events of interest" comprising clinically
      significant bleeding, blood disorders, hepatic dysfunction and other serious
      adverse events up to 12 weeks. The other safety events and vascular events were
      also assessed. Patients were followed up to 52 weeks. RESULTS: A total of 431
      patients with PAD were randomly assigned to receive either clopidogrel or
      ticlopidine. The cumulative incidences of "safety events of interest" at 12 weeks
      were 2.4% and 13.6% of patients who received clopidogrel and ticlopidine,
      respectively (adjusted hazard ratio, 0.161; 95% confidence interval, 0.062 to
      0.416; p <0.0001). Bleeding and vascular events were similar in both groups.
      CONCLUSION: Clopidogrel demonstrated a favorable benefit/risk profile than
      ticlopidine in Japanese patients with PAD. ( TRIAL REGISTRATION:
      ClinicalTrials.gov, Identifier: NCT00862420).

PMID- 23555539
TI  - Renal cell carcinoma with tumor-thrombus extension into the right ventricle.
AB  - Renal cell carcinoma is a tumor with the distinct feature that it can invade
      through the renal vein into the inferior vena cava, and can grow intravascularly,
      sometimes extending into right cardiac chambers. Surgical resection provides the
      only reasonable chance for a cure, and cardiopulmonary bypass with hypothermic
      circulatory arrest is used to resect an intracardiac extension of the tumor
      because the tumor-thrombus adhered strongly to the hepatic vein and to the
      endocardium of the right atrium (RA). We present 2 patients, with renal cell
      carcinoma extending into the right ventricle, who have lived for more than five
      years after the operation.

PMID- 23555540
TI  - A case of pulmonary varix associated with superior pulmonary vein occlusion.
AB  - A pulmonary varix is a localized dilatation of a pulmonary vein, which is usually
      asymptomatic presented as a mass on a chest roentgenogram, and diagnosed with
      pulmonary angiography. We encountered a case of 55 year-old man, in whom
      incidentally identified was a dilated blood vessel that passed through the minor
      fissure and returned to the inferior pulmonary vein, which we diagnosed as
      pulmonary varix. This vascular anomaly was accompanied by the occluded superior
      pulmonary vein, highly suggestive of the developmental mechanism of this disease.

PMID- 23555541
TI  - Acute ischemic pancreatitis associated with acute type B aortic dissection: a
      case report.
AB  - A 47 year-old man, presenting with sudden back pain in the absence of abdominal
      discomfort, was diagnosed with acute type B aortic dissection which extended to
      the celiac and the splenic arteries. Antihypertensive treatment was initiated.
      However, he subsequently complained of upper abdominal pain with increased
      amylase levels. Computed tomography scan (CT) revealed new accumulation of
      peripancreatic fluid with no signs of further aortic or visceral dissection. A
      protease inhibitor was administered for mild acute pancreatitis. Follow-up CT
      demonstrated disappearance of thrombosed false lumen of the splenic artery and
      reduction of the effusion. The patient was discharged without any surgical
      interventions.

PMID- 23555542
TI  - A rare case of septic deep vein thrombosis in the inferior vena cava and the left
      iliac vein in an intravenous drug abuser.
AB  - The patient was a 41 year-old Chinese female, a known intravenous drug abuser
      (IVDA), who presented with a left inguinal discharging sinus. A computed
      tomography (CT) scan showed inflammation in the left groin involving the left
      femoral vein and resulting in thrombus within the iliac veins extending to the
      distal portion of the inferior vena cava. Septic deep vein thrombosis is a well
      recognized complication in intravenous drug abusers (IVDA) when large proximal
      veins are used for drug injection. Life threatening complications such as septic
      pulmonary embolism and right sided infective endocarditis may result. The aims of
      treatment are to prevent the septic thrombus from further embolisation and also
      to remove the thrombus. Treatment options include catheter directed thrombolysis,
      mechanical thrombectomy, endovascular treatment, surgical thrombectomy and
      excision of the involved venous segment.

PMID- 23555547
TI  - Pseudomonas syringae pv. actinidiae from recent outbreaks of kiwifruit bacterial
      canker belong to different clones that originated in China.
AB  - A recently emerged plant disease, bacterial canker of kiwifruit (Actinidia
      deliciosa and A. chinensis), is caused by Pseudomonas syringae pv. actinidiae
      (PSA). The disease was first reported in China and Japan in the 1980s. A severe
      outbreak of PSA began in Italy in 2008 and has spread to other European
      countries. PSA was found in both New Zealand and Chile in 2010. To study the
      evolution of the pathogen and analyse the transmission of PSA between countries,
      genomes of strains from China and Japan (where the genus Actinidia is endemic),
      Italy, New Zealand and Chile were sequenced. The genomes of PSA strains are very
      similar. However, all strains from New Zealand share several single nucleotide
      polymorphisms (SNPs) that distinguish them from all other PSA strains. Similarly,
      all the PSA strains from the 2008 Italian outbreak form a distinct clonal group
      and those from Chile form a third group. In addition to the rare SNPs present in
      the core genomes, there is abundant genetic diversity in a genomic island that is
      part of the accessory genome. The island from several Chinese strains is almost
      identical to the island present in the New Zealand strains. The island from a
      different Chinese strain is identical to the island present in the strains from
      the recent Italian outbreak. The Chilean strains of PSA carry a third variant of
      this island. These genomic islands are integrative conjugative elements (ICEs).
      Sequencing of these ICEs provides evidence of three recent horizontal
      transmissions of ICE from other strains of Pseudomonas syringae to PSA. The
      analyses of the core genome SNPs and the ICEs, combined with disease history, all
      support the hypothesis of an independent Chinese origin for both the Italian and
      the New Zealand outbreaks and suggest the Chilean strains also originate from
      China.

PMID- 23555552
TI  - Visual to Parametric Interaction (V2PI).
AB  - Typical data visualizations result from linear pipelines that start by
      characterizing data using a model or algorithm to reduce the dimension and
      summarize structure, and end by displaying the data in a reduced dimensional
      form. Sensemaking may take place at the end of the pipeline when users have an
      opportunity to observe, digest, and internalize any information displayed.
      However, some visualizations mask meaningful data structures when model or
      algorithm constraints (e.g., parameter specifications) contradict information in
      the data. Yet, due to the linearity of the pipeline, users do not have a natural
      means to adjust the displays. In this paper, we present a framework for creating
      dynamic data displays that rely on both mechanistic data summaries and expert
      judgement. The key is that we develop both the theory and methods of a new human
      data interaction to which we refer as " Visual to Parametric Interaction" (V2PI).
      With V2PI, the pipeline becomes bi-directional in that users are embedded in the
      pipeline; users learn from visualizations and the visualizations adjust to expert
      judgement. We demonstrate the utility of V2PI and a bi-directional pipeline with
      two examples.

PMID- 23555553
TI  - Class prediction and feature selection with linear optimization for metagenomic
      count data.
AB  - The amount of metagenomic data is growing rapidly while the computational methods
      for metagenome analysis are still in their infancy. It is important to develop
      novel statistical learning tools for the prediction of associations between
      bacterial communities and disease phenotypes and for the detection of
      differentially abundant features. In this study, we presented a novel statistical
      learning method for simultaneous association prediction and feature selection
      with metagenomic samples from two or multiple treatment populations on the basis
      of count data. We developed a linear programming based support vector machine
      with L(1) and joint L(1,infinity) penalties for binary and multiclass
      classifications with metagenomic count data (metalinprog). We evaluated the
      performance of our method on several real and simulation datasets. The proposed
      method can simultaneously identify features and predict classes with the
      metagenomic count data.

PMID- 23555554
TI  - Discovery analysis of TCGA data reveals association between germline genotype and
      survival in ovarian cancer patients.
AB  - BACKGROUND: Ovarian cancer remains a significant public health burden, with the
      highest mortality rate of all the gynecological cancers. This is attributable to
      the late stage at which the majority of ovarian cancers are diagnosed, coupled
      with the low and variable response of advanced tumors to standard chemotherapies.
      To date, clinically useful predictors of treatment response remain lacking.
      Identifying the genetic determinants of ovarian cancer survival and treatment
      response is crucial to the development of prognostic biomarkers and personalized
      therapies that may improve outcomes for the late-stage patients who comprise the
      majority of cases. METHODS: To identify constitutional genetic variations
      contributing to ovarian cancer mortality, we systematically investigated
      associations between germline polymorphisms and ovarian cancer survival using
      data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox
      proportional hazards regression, we examined >650,000 SNP loci for association
      with survival. We additionally examined whether the association of significant
      SNPs with survival was modified by somatic alterations. RESULTS: Germline
      polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were
      associated with stage-adjusted survival (p= 1.12e-07 and 1.80e-07, FDR q= 1.2e-04
      and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally
      identified as significant in the exome sequencing data; it is in near-perfect LD
      with rs4934282. The associations with survival remained significant when somatic
      alterations. CONCLUSIONS: Discovery analysis of TCGA data reveals germline
      genetic variations that may play a role in ovarian cancer survival even among
      late-stage cases. The significant loci are located near genes previously reported
      as having a possible relationship to platinum and taxol response. Because the
      variant alleles at the significant loci are common (frequencies for rs4934282 A/C
      alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45,
      respectively) and germline variants can be assayed noninvasively, our findings
      provide potential targets for further exploration as prognostic biomarkers and
      individualized therapies.

PMID- 23555555
TI  - Reduced estradiol-induced vasodilation and poly-(ADP-ribose) polymerase (PARP)
      activity in the aortas of rats with experimental polycystic ovary syndrome
      (PCOS).
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by
      hyperandrogenism and insulin resistance, both of which have been connected to
      atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial
      vascular diseases has been described in PCOS. On the other hand endothelial
      dysfunction can be detected early on, before atherosclerosis develops. Thus we
      assumed that vascular dysfunction is also related directly to the hormonal
      imbalance rather than to its metabolic consequences. To detect early functional
      changes, we applied a novel rodent model of PCOS: rats were either sham operated
      or hyperandrogenism was achieved by implanting subcutaneous pellets of
      dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed
      on isolated aortic rings. Previously we described an increased contractility to
      norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol
      treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the
      administration of vitamin D3 along with DHT reduced responsiveness to NE, it did
      not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity
      was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries
      and circulating leukocytes from DHT rats showed enhanced DNA damage, which was
      reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was
      reduced in both the endothelium and vascular smooth muscle cells of the aorta
      rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone
      is already shifted towards vasoconstriction, characterized by reduced
      vasorelaxation and vascular dysfunction is concomitant with altered PARP
      activity. Based on our findings, PARP inhibitors might have a future perspective
      in restoring metabolic disorders in PCOS.

PMID- 23555557
TI  - Effects of decabromodiphenyl ether (BDE-209) on inter-specific competition
      between two species of marine bloom-forming microalgae.
AB  - Decabromodiphenyl ether (BDE-209), a new kind of persistent organic pollutants,
      was selected to investigate its influence on population growth and inter-specific
      competition between two species of marine bloom-forming microalgae, Heterosigma
      akashiwo and Karenia mikimotoi. (1)BDE-209 showed acute toxic effects on both
      microalgae and H. akashiwo was more sensitive from view of 96 h-EC50 and the
      ultrastructure variation. (2)The microalgal population growth patterns in mono
      culture were density-dependent and the growth of both species in the normal co
      culture was significantly depressed by competition (P<0.05) with different
      initial biomass ratios. BDE-209 exposure significantly changed the growth. (3)
      Lotka-Volterra competition model was used to simulate the interaction between the
      microalgae. BDE-209 exposure broke the competitive balance to make competition
      gradually shift in favor of H. akashiwo. Results suggested BDE-209 did have toxic
      effects on either microalgal growth or the inter-specific competition, which was
      quite different from previous reports. Further exploration of the mechanism is
      needed.

PMID- 23555556
TI  - Morphine induces albuminuria by compromising podocyte integrity.
AB  - Morphine has been reported to accelerate the progression of chronic kidney
      disease. However, whether morphine affects slit diaphragm (SD), the major
      constituent of glomerular filtration barrier, is still unclear. In the present
      study, we examined the effect of morphine on glomerular filtration barrier in
      general and podocyte integrity in particular. Mice were administered either
      normal saline or morphine for 72 h, then urine samples were collected and kidneys
      were subsequently isolated for immunohistochemical studies and Western blot. For
      in vitro studies, human podocytes were treated with morphine and then probed for
      the molecular markers of slit diaphragm. Morphine-receiving mice displayed a
      significant increase in albuminuria and showed effacement of podocyte foot
      processes. In both in vivo and in vitro studies, the expression of synaptopodin,
      a molecular marker for podocyte integrity, and the slit diaphragm constituting
      molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP),
      were decreased in morphine-treated podocytes. In vitro studies indicated that
      morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa
      (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the
      latter seems to contribute to decreased SDCM expression. In addition, AKT, p38,
      and JNK pathways were involved in morphine-induced down regulation of SDCM in
      human podocytes. These findings demonstrate that morphine has the potential to
      alter the glomerular filtration barrier by compromising the integrity of
      podocytes.

PMID- 23555558
TI  - Induction of olfaction and cancer-related genes in mice fed a high-fat diet as
      assessed through the mode-of-action by network identification analysis.
AB  - The pathophysiological mechanisms underlying the development of obesity and
      metabolic diseases are not well understood. To gain more insight into the genetic
      mediators associated with the onset and progression of diet-induced obesity and
      metabolic diseases, we studied the molecular changes in response to a high-fat
      diet (HFD) by using a mode-of-action by network identification (MNI) analysis.
      Oligo DNA microarray analysis was performed on visceral and subcutaneous adipose
      tissues and muscles of male C57BL/6N mice fed a normal diet or HFD for 2, 4, 8,
      and 12 weeks. Each of these data was queried against the MNI algorithm, and the
      lists of top 5 highly ranked genes and gene ontology (GO)-annotated pathways that
      were significantly overrepresented among the 100 highest ranked genes at each
      time point in the 3 different tissues of mice fed the HFD were considered in the
      present study. The 40 highest ranked genes identified by MNI analysis at each
      time point in the different tissues of mice with diet-induced obesity were
      subjected to clustering based on their temporal patterns. On the basis of the
      above-mentioned results, we investigated the sequential induction of distinct
      olfactory receptors and the stimulation of cancer-related genes during the
      development of obesity in both adipose tissues and muscles. The top 5 genes
      recognized using the MNI analysis at each time point and gene cluster identified
      based on their temporal patterns in the peripheral tissues of mice provided novel
      and often surprising insights into the potential genetic mediators for obesity
      progression.

PMID- 23555559
TI  - Critical role of H2O2 generated by NOX4 during cellular response under glucose
      deprivation.
AB  - Glucose is the most efficient energy source, and various cancer cells depend on
      glycolysis for energy production. For maintenance of survival and proliferation,
      glucose sensing and adaptation to poor nutritional circumstances must be well
      organized in cancer cells. While the glucose sensing machinery has been well
      studied in yeasts, the molecular mechanism of glucose sensing in mammalian cells
      remains to be elucidated. We have reported glucose deprivation rapidly induces
      AKT phosphorylation through PI3K activation. We assumed that regulation of AKT is
      relevant to glucose sensing and further investigated the underlying mechanisms.
      In this study, AKT phosphorylation under glucose deprivation was inhibited by
      galactose and fructose, but induced by 2-deoxyglucose (2-DG). Both 2-DG treatment
      and glucose deprivation were found to induce AKT phosphorylation in HepG2 cells.
      These findings suggested that glucose transporter may not be involved in the
      sensing of glucose and induction of AKT phosphorylation, and that downstream
      metabolic events may have important roles. A variety of metabolic stresses
      reportedly induce the production of reactive oxygen species (ROS). In the present
      study, glucose deprivation was found to induce intracellular hydrogen peroxide
      (H2O2) production in HepG2 cells. N-acetylcysteine (NAC), an antioxidant reagent,
      reduced both the increase in cellular H2O2 levels and AKT phosphorylation induced
      by glucose deprivation. These results strongly suggest that the glucose
      deprivation-induced increase of H2O2 in the cells mediated the AKT
      phosphorylation. RNA interference of NOX4, but not of NOX5, completely suppressed
      the glucose deprivation-induced AKT phosphorylation as well as increase of the
      intracellular levels of ROS, whereas exogenous H2O2 could still induce AKT
      phosphorylation in the NOX4-knockdown cells. In this study, we demonstrated that
      the ROS generated by NOX4 are involved in the intracellular adaptive responses by
      recognizing metabolic flux.

PMID- 23555560
TI  - Absence of TLR4 reduces neurovascular unit and secondary inflammatory process
      after traumatic brain injury in mice.
AB  - BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade
      that contributes to neuronal damage and behavioral impairment. Toll-like
      receptors (TLRs) are signaling receptors in the innate immune system, although
      emerging evidence indicates their role in brain injury. We have therefore
      investigated the role played by TLR4 signaling pathway in the development of
      mechanisms of secondary inflammatory process in traumatic brain injury (TBI)
      differ in mice that lack a functional TLR4 signaling pathway. METHODS/PRINCIPAL
      FINDINGS: Controlled cortical impact injury was performed on TLR4 knockout (KO)
      mice (C57BL/10ScNJ) and wild-type (WT) mice (C57BL/10ScNJ). TBI outcome was
      evaluated by determination of infarct volume and assessment of neurological
      scores. Brains were collected at 24 h after TBI. When compared to WT mice, TLR4
      KO mice had lower infarct volumes and better outcomes in neurological and
      behavioral tests (evaluated by EBST and rotarod test). Mice that lacked TLR4 had
      minor expression of TBI-induced GFAP, Chymase, Tryptase, IL-1beta, iNOS, PARP and
      Nitrotyrosine mediators implicated in brain damage. The translocation of
      expression of p-JNK, IkappaB-alpha and NF-kappaB pathway were also lower in
      brains from TLR4 KO mice. When compared to WT mice, resulted in significant
      augmentation of all the above described parameters. In addition, apoptosis levels
      in TLR4 KO mice had minor expression of Bax while on the contrary with Bcl-2.
      CONCLUSIONS/SIGNIFICANCE: Our results clearly demonstrated that absence of TLR4
      reduces the development of neuroinflammation, tissues injury events associated
      with brain trauma and may play a neuroprotective role in TBI in mice.

PMID- 23555562
TI  - QTL mapping based on different genetic systems for essential amino acid contents
      in cottonseeds in different environments.
AB  - Cottonseeds are rich in various essential amino acids. However, the inheritance
      of them at molecular level are still not defined across various genetic systems.
      In the present study, using a newly developed mapping model that can analyze the
      embryo and maternal main effects as well as QTL * environment interaction effects
      on quantitative quality trait loci (QTLs) in cottonseeds, a study on QTL located
      in the tetraploid embryo and tetraploid maternal plant genomes for essential
      amino acid contents in cottonseeds under different environments was carried out,
      using the immortal F2 (IF2) populations from a set of 188 recombinant inbred
      lines derived from an intraspecific hybrid cross of two upland cotton germplasms
      HS46 and MARKCBUCAG8US-1-88 as experimental materials. The results showed a total
      of 35 QTLs associated with these quality traits in cottonseeds. Nineteen QTLs
      were subsequently mapped on chromosome 5, 6 and 8 in sub-A genome and chromosome
      15, 18, 22 and 23 in sub-D genome. Eighteen QTLs were also found having QTL *
      environment (QE) interaction effects. The genetic main effects from QTLs located
      on chromosomes in the embryo and maternal plant genomes and their QE effects in
      different environments were all important for these essential amino acids in
      cottonseeds. The results suggested that the influence of environmental factors on
      the expression of some QTLs located in different genetic systems should be
      considered when improving for these amino acids. This study can serve as the
      foundation for the improvement of these essential amino acids in cottonseeds.

PMID- 23555561
TI  - Smoking ban and small-for-gestational age births in Ireland.
AB  - BACKGROUND: Ireland introduced a comprehensive workplace smoke-free legislation
      in March, 2004. Smoking-related adverse birth outcomes have both health care and
      societal cost implications. The main aim of this study was to determine the
      impact of the Irish smoke-free legislation on small-for-gestationa- age (SGA)
      births. METHODS AND FINDINGS: We developed a population-based birthweight (BW)
      percentile curve based on a recent study to compute SGA (BW <5(th) percentile)
      and very SGA (vSGA - BW<3(rd) percentile) for each gestational week. Monthly
      births born between January 1999 and December 2008 were analyzed linking with
      monthly maternal smoking rates from a large referral maternity university
      hospital. We ran individual control and CUSUM charts, with bootstrap simulations,
      to pinpoint the breakpoint for the impact of ban implementation ( = April 2004).
      Monthly SGA rates (%) before and after April 2004 was considered pre and post ban
      period births, respectively. Autocorrelation was tested using Durbin Watson (DW)
      statistic. Mixed models using a random intercept and a fixed effect were employed
      using SAS (v 9.2). A total of 588,997 singleton live-births born between January
      1999 and December 2008 were analyzed. vSGA and SGA monthly rates declined from an
      average of 4.7% to 4.3% and from 6.9% to 6.6% before and after April 2004,
      respectively. No auto-correlation was detected (DW = ~2). Adjusted mixed models
      indicated a significant decline in both vSGA and SGA rates immediately after the
      ban [(-5.3%; 95% CI -5.43% to -5.17%, p<0.0001) and (-0.45%; 95% CI: -0.7% to 
      0.19%, p<0.0007)], respectively. Significant gradual effects continued post the
      ban periods for vSGA and SGA rates, namely, -0.6% (p<0.0001) and -0.02%
      (p<0.0001), respectively. CONCLUSIONS: A significant reduction in small-for
      gestational birth rates both immediately and sustained over the post-ban period,
      reinforces the mounting evidence of the positive health effect of a successful
      comprehensive smoke-free legislation in a vulnerable population group as pregnant
      women.

PMID- 23555563
TI  - Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno
      associated virus encoding a monoclonal antibody targeting the amyloid Beta
      protein.
AB  - We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta
      (Abeta) protein. Repeated injection of that mAb reduced the accumulation of Abeta
      protein in the brain of human Abeta transgenic mice (Tg2576). In the present
      study, cDNA encoding the heavy and light chains of this mAb were subcloned into
      an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single
      intramuscular injection of 3.0*10(10) viral genome of these AAV vectors into
      C57BL/6 mice generated serum anti-Abeta Ab levels up to 0.3 mg/ml. Anti-Abeta Ab
      levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of
      AAV administration on Abeta levels in vivo was examined. A significant decrease
      in Abeta levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or
      10 months (therapeutic) of age was observed. These results support the use of AAV
      vector encoding anti-Abeta Ab for the prevention and treatment of Alzheimer's
      disease.

PMID- 23555564
TI  - Active-duty physicians' perceptions and satisfaction with humanitarian assistance
      and disaster relief missions: implications for the field.
AB  - BACKGROUND: The United States Department of Defense participates in more than 500
      missions every year, including humanitarian assistance and disaster relief, as
      part of medical stability operations. This study assessed perceptions of active
      duty physicians regarding these activities and related these findings to the
      retention and overall satisfaction of healthcare professionals. METHODS AND
      FINDINGS: An Internet-based survey was developed and validated. Of the 667
      physicians who responded to the survey, 47% had participated in at least one
      mission. On a 7-point, Likert-type response scale, physicians reported favorable
      overall satisfaction with their participation in these missions (mean = 5.74).
      Perceived benefit was greatest for the United States (mean = 5.56) and self (mean
      = 5.39) compared to the target population (mean = 4.82). These perceptions were
      related to participants' intentions to extend their military medical service
      (total model R (2) = .37), with the strongest predictors being perceived benefit
      to self (beta = .21, p<.01), the U.S. (beta = .19, p<.01), and satisfaction (beta
      = .18, p<.05). In addition, Air Force physicians reported higher levels of
      satisfaction (mean = 6.10) than either Army (mean = 5.27, Cohen's d = 0.75,
      p<.001) or Navy (mean = 5.60, Cohen's d = 0.46, p<.01) physicians. CONCLUSIONS:
      Military physicians are largely satisfied with humanitarian missions, reporting
      the greatest benefit of such activities for themselves and the United States.
      Elucidation of factors that may increase the perceived benefit to the target
      populations is warranted. Satisfaction and perceived benefits of humanitarian
      missions were positively correlated with intentions to extend time in service.
      These findings could inform the larger humanitarian community as well as military
      medical practices for both recruiting and retaining medical professionals.

PMID- 23555565
TI  - Quantitative susceptibility mapping differentiates between blood depositions and
      calcifications in patients with glioblastoma.
AB  - OBJECTIVES: The application of susceptibility weighted imaging (SWI) in brain
      tumor imaging is mainly used to assess tumor-related "susceptibility based
      signals" (SBS). The origin of SBS in glioblastoma is still unknown, potentially
      representing calcifications or blood depositions. Reliable differentiation
      between both entities may be important to evaluate treatment response and to
      identify glioblastoma with oligodendroglial components that are supposed to
      present calcifications. Since calcifications and blood deposits are difficult to
      differentiate using conventional MRI, we investigated whether a new post
      processing approach, quantitative susceptibility mapping (QSM), is able to
      distinguish between both entities reliably. MATERIALS AND METHODS: SWI, FLAIR,
      and T1-w images were acquired from 46 patients with glioblastoma (14 newly
      diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy
      and additional anti-angiogenic medication). Susceptibility maps were calculated
      from SWI data. All glioblastoma were evaluated for the appearance of hypointense
      or hyperintense correlates of SBS on the susceptibility maps. RESULTS: 43 of 46
      glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps,
      indicating blood deposits. Additional hypointense correlates of tumor-related SBS
      on susceptibility maps, indicating calcification, were identified in 2 patients
      being treated with radiochemotherapy and in one patient being treated with
      additional anti-angiogenic medication. Histopathologic reports revealed an
      oligodendroglial component in one patient that presented calcifications on
      susceptibility maps. CONCLUSIONS: QSM provides a quantitative, local MRI
      contrast, which reliably differentiates between blood deposits and
      calcifications. Thus, quantitative susceptibility mapping appears promising to
      identify rare variants of glioblastoma with oligodendroglial components non
      invasively and may allow monitoring the role of calcification in the context of
      different therapy regimes.

PMID- 23555566
TI  - Nanoscale probing of thermal, stress, and optical fields under near-field laser
      heating.
AB  - Micro/nanoparticle induced near-field laser ultra-focusing and heating has been
      widely used in laser-assisted nanopatterning and nanolithography to pattern
      nanoscale features on a large-area substrate. Knowledge of the temperature and
      stress in the nanoscale near-field heating region is critical for process control
      and optimization. At present, probing of the nanoscale temperature, stress, and
      optical fields remains a great challenge since the heating area is very small
      (~100 nm or less) and not immediately accessible for sensing. In this work, we
      report the first experimental study on nanoscale mapping of particle-induced
      thermal, stress, and optical fields by using a single laser for both near-field
      excitation and Raman probing. The mapping results based on Raman intensity
      variation, wavenumber shift, and linewidth broadening all give consistent
      conjugated thermal, stress, and near-field focusing effects at a 20 nm resolution
      (<lambda/26, lambda = 32 nm). Nanoscale mapping of near-field effects of
      particles from 1210 down to 160 nm demonstrates the strong capacity of such a
      technique. By developing a new strategy for physical analysis, we have de
      conjugated the effects of temperature, stress, and near-field focusing from the
      Raman mapping. The temperature rise and stress in the nanoscale heating region is
      evaluated at different energy levels. High-fidelity electromagnetic and
      temperature field simulation is conducted to accurately interpret the
      experimental results.

PMID- 23555567
TI  - Effects of cyclic intermittent hypoxia on ET-1 responsiveness and endothelial
      dysfunction of pulmonary arteries in rats.
AB  - Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular disorders and
      in some cases is complication of pulmonary hypertension. We simulated OSA by
      exposing rats to cyclic intermittent hypoxia (CIH) to investigate its effect on
      pulmonary vascular endothelial dysfunction. Sprague-Dawley Rats were exposed to
      CIH (FiO2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/wk for 3 wk),
      and the pulmonary arteries of normoxia and CIH treated rats were analyzed for
      expression of endothelin-1 (ET-1) and ET receptors by histological,
      immunohistochemical, RT-PCR and Western Blot analyses, as well as for
      contractility in response to ET-1. In the pulmonary arteries, ET-1 expression was
      increased, and ET-1 more potently elicited constriction of the pulmonary artery
      in CIH rats than in normoxic rats. Exposure to CIH induced marked endothelial
      cell damage associated with a functional decrease of endothelium-dependent
      vasodilatation in the pulmonary artery. Compared with normoxic rats, ETA receptor
      expression was increased in smooth muscle cells of the CIH rats, while the
      expression of ETB receptors was decreased in endothelial cells. These results
      demonstrated endothelium-dependent vasodilation was impaired and the
      vasoconstrictor responsiveness increased by CIH. The increased responsiveness to
      ET-1 induced by intermittent hypoxia in pulmonary arteries of rats was due to
      increased expression of ETA receptors predominantly, meanwhile, decreased
      expression of ETB receptors in the endothelium may also participate in it.

PMID- 23555568
TI  - Do active surveillance and contact precautions reduce MRSA acquisition? A
      prospective interrupted time series.
AB  - BACKGROUND: Consensus for methicillin-resistant Staphylococcus aureus (MRSA)
      control has still not been reached. We hypothesised that use of rapid MRSA
      detection followed by contact precautions and single room isolation would reduce
      MRSA acquisition. METHODS: This study was a pre-planned prospective interrupted
      time series comparing rapid PCR detection and use of long sleeved gowns and
      gloves (contact precautions) plus single room isolation or cohorting of MRSA
      colonised patients with a control group. The study took place in a medical
      surgical intensive care unit of a tertiary adult hospital between May 21(st) 2007
      and September 21(st) 2009. The primary outcome was the rate of MRSA acquisition.
      A segmented regression analysis was performed to determine the trend in MRSA
      acquisition rates before and after the intervention. FINDINGS: The rate of MRSA
      acquisition was 18.5 per 1000 at risk patient days in the control phase and 7.9
      per 1000 at-risk patient days in the intervention phase, with an adjusted hazard
      ratio 0.39 (95% CI 0.24 to 0.62). Segmented regression analysis showed a decline
      in MRSA acquisition of 7% per month in the intervention phase, (95%CI 1.9% to
      12.8% reduction) which was a significant change in slope compared with the
      control phase. Secondary analysis found prior exposure to anaerobically active
      antibiotics and colonization pressure were associated with increased acquisition
      risk. CONCLUSION: Contact precautions with single room isolation or cohorting
      were associated with a 60% reduction in MRSA acquisition. While this study was a
      quasi-experimental design, many measures were taken to strengthen the study, such
      as accounting for differences in colonisation pressure, hand hygiene compliance
      and individual risk factors across the groups, and confining the study to one
      centre to reduce variation in transmission. Use of two research nurses may limit
      its generalisability to units in which this level of support is available.

PMID- 23555570
TI  - Single unpurified breast tumor-initiating cells from multiple mouse models
      efficiently elicit tumors in immune-competent hosts.
AB  - The tumor-initiating cell (TIC) frequency of bulk tumor cell populations is one
      of the criteria used to distinguish malignancies that follow the cancer stem cell
      model from those that do not. However, tumor-initiating cell frequencies may be
      influenced by experimental conditions and the extent to which tumors have
      progressed, parameters that are not always addressed in studies of these cells.
      We employed limiting dilution cell transplantation of minimally manipulated tumor
      cells from mammary tumors of several transgenic mouse models to determine their
      tumor-initiating cell frequency. We determined whether the tumors that formed
      following tumor cell transplantation phenocopied the primary tumors from which
      they were isolated and whether they could be serially transplanted. Finally we
      investigated whether propagating primary tumor cells in different tissue culture
      conditions affected their resident tumor-initiating cell frequency. We found that
      tumor-initiating cells comprised between 15% and 50% of the bulk tumor cell
      population in multiple independent mammary tumors from three different transgenic
      mouse models of breast cancer. Culture of primary mammary tumor cells in
      chemically-defined, serum-free medium as non-adherent tumorspheres preserved TIC
      frequency to levels similar to that of the primary tumors from which they were
      established. By contrast, propagating the primary tumor cells in serum-containing
      medium as adherent populations resulted in a several thousand-fold reduction in
      their tumor-initiating cell fraction. Our findings suggest that experimental
      conditions, including the sensitivity of the transplantation assay, can
      dramatically affect estimates of tumor initiating cell frequency. Moreover,
      conditional on cell culture conditions, the tumor-initiating cell fraction of
      bulk mouse mammary tumor cell preparations can either be maintained at high or
      low frequency in vitro thus permitting comparative studies of tumorigenic and non
      tumorigenic cancer cells.

PMID- 23555569
TI  - Levels of lycopene beta-cyclase 1 modulate carotenoid gene expression and
      accumulation in Daucus carota.
AB  - Plant carotenoids are synthesized and accumulated in plastids through a highly
      regulated pathway. Lycopene beta-cyclase (LCYB) is a key enzyme involved directly
      in the synthesis of alpha-carotene and beta-carotene through the cyclization of
      lycopene. Carotenoids are produced in both carrot (Daucus carota) leaves and
      reserve roots, and high amounts of alpha-carotene and beta-carotene accumulate in
      the latter. In some plant models, the presence of different isoforms of
      carotenogenic genes is associated with an organ-specific function. D. carota
      harbors two Lcyb genes, of which DcLcyb1 is expressed in leaves and storage roots
      during carrot development, correlating with an increase in carotenoid levels. In
      this work, we show that DcLCYB1 is localized in the plastid and that it is a
      functional enzyme, as demonstrated by heterologous complementation in Escherichia
      coli and over expression and post transcriptional gene silencing in carrot.
      Transgenic plants with higher or reduced levels of DcLcyb1 had incremented or
      reduced levels of chlorophyll, total carotenoids and beta-carotene in leaves and
      in the storage roots, respectively. In addition, changes in the expression of
      DcLcyb1 are accompanied by a modulation in the expression of key endogenous
      carotenogenic genes. Our results indicate that DcLcyb1 does not possess an organ
      specific function and modulate carotenoid gene expression and accumulation in
      carrot leaves and storage roots.

PMID- 23555571
TI  - Factors associated with esophageal candidiasis and its endoscopic severity in the
      era of antiretroviral therapy.
AB  - BACKGROUND: Candidia esophagitis (CE) is an AIDS-defining condition, usually
      occurring in individuals with low CD4 counts of <200 cells/uL. Endoscopy is a
      valuable definitive diagnostic method for CE but may not be indicated for
      asymptomatic patients or for those with high CD4 counts or without oral
      candidiasis. This study assessed such patients to clarify the factors associated
      with CE and its severity on endoscopy in the highly active antiretroviral therapy
      (HAART) era. METHODOLOGY PRINCIPAL FINDINGS: A total of 733 HIV-infected patients
      who underwent upper gastrointestinal (GI) endoscopy were analyzed. Sexual
      behavior, CD4(+) count, HIV-RNA viral load (VL), history of HAART, GI symptoms,
      GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was
      classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of the 733
      subjects, 62 (8.46%) were diagnosed with CE (mild, n = 33; severe, n = 29). Of
      them, 56.5% (35/62) had no GI symptoms, 30.6% (19/62) had CD4 + >=200 cells/MUL,
      and 55.3% (21/38) had no oral candidiasis. Univariate analysis found lower CD4+
      counts, higher HIV VL, and no history of HAART to be significantly associated
      with CE. With lower CD4(+) counts and higher HIV VL, CE occurrence increased
      significantly (P<0.01 for trend in odds). Multivariate analysis showed low CD4+
      counts and high HIV VL to be independently associated with CE. Of the severe CE
      patients, 55.2% (16/29) had no GI symptoms and 44.4% (8/18) had no oral
      candidiasis. Median CD4(+) counts in severe cases were significantly lower than
      in mild cases (27 vs. 80; P = 0.04). CONCLUSIONS: Low CD4+ counts and high HIV VL
      were found to be factors associated with CE, and advanced immunosuppression was
      associated with the development of severity. Endoscopy is useful as it can detect
      CE, even severe CE, in patients without GI symptoms, those with high CD4 counts,
      and those without oral candidiasis.

PMID- 23555572
TI  - Neurocognitive and somatic components of temperature increases during g-tummo
      meditation: legend and reality.
AB  - Stories of g-tummo meditators mysteriously able to dry wet sheets wrapped around
      their naked bodies during a frigid Himalayan ceremony have intrigued scholars and
      laypersons alike for a century. Study 1 was conducted in remote monasteries of
      eastern Tibet with expert meditators performing g-tummo practices while their
      axillary temperature and electroencephalographic (EEG) activity were measured.
      Study 2 was conducted with Western participants (a non-meditator control group)
      instructed to use the somatic component of the g-tummo practice (vase breathing)
      without utilization of meditative visualization. Reliable increases in axillary
      temperature from normal to slight or moderate fever zone (up to 38.3 degrees C)
      were observed among meditators only during the Forceful Breath type of g-tummo
      meditation accompanied by increases in alpha, beta, and gamma power. The
      magnitude of the temperature increases significantly correlated with the
      increases in alpha power during Forceful Breath meditation. The findings indicate
      that there are two factors affecting temperature increase. The first is the
      somatic component which causes thermogenesis, while the second is the
      neurocognitive component (meditative visualization) that aids in sustaining
      temperature increases for longer periods. Without meditative visualization, both
      meditators and non-meditators were capable of using the Forceful Breath vase
      breathing only for a limited time, resulting in limited temperature increases in
      the range of normal body temperature. Overall, the results suggest that specific
      aspects of the g-tummo technique might help non-meditators learn how to regulate
      their body temperature, which has implications for improving health and
      regulating cognitive performance.

PMID- 23555573
TI  - Selective impact of early parental responsivity on adolescent stress reactivity.
AB  - Research in animals has shown that early life experience, particularly parenting
      behaviors, influences later-life stress reactivity. Despite the tremendous
      relevance of this finding to human development and brain function, it has not
      been tested prospectively in humans. In this study two aspects of parenting were
      measured at age 4 in a sample of healthy, low socioeconomic status, African
      American children, and stress reactivity was measured in the same children 11-14
      years later using a modified version of the Trier Social Stress Test (n = 55).
      Salivary cortisol was measured before, during and after the stressor and data
      were analyzed using piecewise hierarchical linear modeling. Parental
      responsivity, independent of the use of physical discipline, was positively
      related to cortisol reactivity. Effects were independent of subjective appraisals
      of the stressor and were also independent of other environmental risk factors and
      current psychosocial functioning. Therefore this study demonstrates in a novel
      and precise fashion that early childhood parental responsivity prospectively and
      independently predicts stress reactivity in adolescence.

PMID- 23555574
TI  - Expression of estrogen receptor alpha 36 (ESR36) in the hamster ovary throughout
      the estrous cycle: effects of gonadotropins.
AB  - Estradiol-17beta (E) plays an important role in ovarian follicular development.
      Evidence indicates that some of the effect of E is mediated by the transmembrane
      estrogen receptor. In this study, we examined the spatio-temporal expression of
      recently discovered ERalpha36 (ESR36), a splice variant of Esr1 and a receptor
      for non-genomic E signaling, in the hamster ovary during the estrous cycle and
      the role of gonadotropins and ovarian steroid hormones in ESR36 expression. ESR36
      expression was high on estrus (D1:0900 h) and declined precipitously by proestrus
      (D4:0900 h) and remained low up to D4:1600 h. Immunofluorescence findings
      corroborated immunoblot findings and revealed that ESR36 was expressed only in
      the cell membrane of both follicular and non-follicular cells, except the
      oocytes. Ovarian ESR36 was capable of binding to the E-affinity matrix, and have
      different molecular weight than that of the ESR1 or GPER. Hypophysectomy (Hx)
      resulted in a marked decline in ESR36 protein levels. FSH and LH, alone or
      combined, markedly upregulated ESR36 protein in Hx hamsters to the levels
      observed in D1 hamsters, but neither E nor P had any effect. Inhibition of the
      gonadotropin surge by phenobarbital treatment on D4:1100 h attenuated ESR36
      expression in D1:0900 h ovaries, but the decline was restored by either FSH or LH
      replacement on D4 afternoon. This is the first report to show that ESR36, which
      is distinct from ESR1 or GPER is expressed in the plasma membrane of ovarian
      follicular and non-follicular cells, binds to E and its expression is regulated
      directly by the gonadotropins. In light of our previous findings, the results
      suggest that ovarian cells contain at least two distinct membrane estrogen
      receptors, such as GPER and ESR36, and strongly suggest for a non-genomic action
      of E regulating ovarian follicular functions.

PMID- 23555575
TI  - Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3)
      suppresses murine colon cancer.
AB  - Ptp4a3 (commonly known as PRL-3) is an enigmatic member of the Ptp4a family of
      prenylated protein tyrosine phosphatases that are highly expressed in many human
      cancers. Despite strong correlations with tumor metastasis and poor patient
      prognosis, there is very limited understanding of this gene family's role in
      malignancy. Therefore, we created a gene-targeted murine knockout model for
      Ptp4a3, the most widely studied Ptp4a family member. Mice deficient for Ptp4a3
      were grossly normal. Fewer homozygous-null males were observed at weaning,
      however, and they maintained a decreased body mass. Although Ptp4a3 is normally
      associated with late-stage cancer and metastasis, we observed increased Ptp4a3
      expression in the colon of wildtype mice immediately following treatment with the
      carcinogen azoxymethane. To investigate the role of Ptp4a3 in malignancy, we used
      the most commonly studied murine colitis-associated colon cancer model. Wildtype
      mice treated with azoxymethane and dextran sodium sulfate developed approximately
      7-10 tumors per mouse in the distal colon. The resulting tumor tissue had 4-fold
      more Ptp4a3 mRNA relative to normal colon epithelium and increased PTP4A3
      protein. Ptp4a3-null mice developed 50% fewer colon tumors than wildtype mice
      after exposure to azoxymethane and dextran sodium sulfate. Tumors from the Ptp4a3
      null mice had elevated levels of both IGF1Rbeta and c-MYC compared to tumors
      replete with Ptp4a3, suggesting an enhanced cell signaling pathway engagement in
      the absence of the phosphatase. These results provide the first definitive
      evidence implicating Ptp4a3 in colon tumorigenesis and highlight the potential
      value of the phosphatase as a therapeutic target for early stage malignant
      disease.

PMID- 23555576
TI  - A broad profile of co-dominant epitopes shapes the peripheral Mycobacterium
      tuberculosis specific CD8+ T-cell immune response in South African patients with
      active tuberculosis.
AB  - We studied major histocompatibility complex (MHC) class I peptide-presentation
      and nature of the antigen-specific CD8+ T-cell response from South African
      tuberculosis (TB) patients with active TB. 361 MHC class I binding epitopes were
      identified from three immunogenic TB proteins (ESAT-6 [Rv3875], Ag85B [Rv1886c],
      and TB10.4 [Rv0288], including amino acid variations for Rv0288, i.e., A10T,
      G13D, S27N, and A71S for MHC allotypes common in a South African population
      (e.g., human leukocyte antigen [HLA]-A*30, B*58, and C*07). Inter-allelic
      differences were identified regarding the broadness of the peptide-binding
      capacity. Mapping of frequencies of Mycobacterium tuberculosis (M. tb) antigen
      specific CD8+ T-cells using 48 different multimers, including the newly
      constructed recombinant MHC class I alleles HLA-B*58:01 and C*0701, revealed a
      low frequency of CD8+ T-cell responses directed against a broad panel of co
      dominant M. tb epitopes in the peripheral circulation of most patients. The
      antigen-specific responses were dominated by CD8+ T-cells with a precursor-like
      phenotype (CD45RA+CCR7+). The data show that the CD8+ T-cell response from
      patients with pulmonary TB (prior to treatment) is directed against subdominant
      epitopes derived from secreted and non-secreted M. tb antigens and that variant,
      natural occurring M. tb Rv0288 ligands, have a profound impact on T-cell
      recognition.

PMID- 23555577
TI  - Identification of relevant conformational epitopes on the HER2 oncoprotein by
      using Large Fragment Phage Display (LFPD).
AB  - We developed a new phage-display based approach, the Large Fragment Phage Display
      (LFPD), that can be used for mapping conformational epitopes on target molecules
      of immunological interest. LFPD uses a simplified and more effective phage
      display approach in which only a limited set of larger fragments (about 100 aa in
      length) are expressed on the phage surface. Using the human HER2 oncoprotein as a
      target, we identified novel B-cell conformational epitopes. The same homologous
      epitopes were also detected in rat HER2 and all corresponded to the epitopes
      predicted by computational analysis (PEPITO software), showing that LFPD gives
      reproducible and accurate results. Interestingly, these newly identified HER2
      epitopes seem to be crucial for an effective immune response against HER2
      overexpressing breast cancers and might help discriminating between metastatic
      breast cancer and early breast cancer patients. Overall, the results obtained in
      this study demonstrated the utility of LFPD and its potential application to the
      detection of conformational epitopes on many other molecules of interest, as well
      as, the development of new and potentially more effective B-cell conformational
      epitopes based vaccines.

PMID- 23555578
TI  - NIKEI: a new inexpensive and non-invasive scoring system to exclude advanced
      fibrosis in patients with NAFLD.
AB  - AIMS: To develop, validate and compare a non-invasive fibrosis scoring system for
      non-alcoholic fatty liver disease (NAFLD) derived from routinely obtained
      clinical and biochemical parameters. METHODS: 267 consecutive patients with
      biopsy proven fatty liver or non-alcoholic steatohepatitis were randomly assigned
      to the estimation (2/3) or validation (1/3) group to develop a model for the
      prediction of advanced fibrosis. Univariate statistics were performed to compare
      patients with and without advanced fibrosis, and following a multivariate
      logistic regression analysis a new scoring system was constructed. This non
      invasive Koeln-Essen-index (NIKEI) was validated and compared to the FIB-4 index
      by calculating the area under the receiver operating characteristic curve (AUC).
      We evaluated a stepwise combination of both scoring systems for the precise
      prediction of advanced fibrosis. To set in contrast, we additionally tested the
      diagnostic accuracy of the AST/ALT ratio, BARD score and the NAFLD fibrosis score
      in our cohort. RESULTS: Age, AST, AST/ALT ratio, and total bilirubin were
      identified as significant predictors of advanced fibrosis and used to construct
      the NIKEI with an AUC of 0.968 [0.937; 0.998] compared to 0.929 [0.869; 0.989]
      for the FIB-4 index. The absence of advanced fibrosis could be confirmed with
      excellent accuracy (99-100%). The positive predictive value of the FIB-4 index
      was higher (100% vs. 60%), however, the false negative rate was also high (33%).
      With a stepwise combination of both indices 82%-84% of biopsies would have been
      avoidable without a single misclassification. The AUROC for AST/ALT ratio, the
      NAFLD fibrosis score, and the BARD score were 0.81 (95% CI, 0.72-0.90), 0.96 (95%
      CI 0.92-0.99), and 0.67 (95% CI 0.55-0.78), respectively. CONCLUSION: The NIKEI
      can reliably exclude advanced fibrosis in subjects with NAFLD. In combination
      with the FIB-4 index misclassification with inadequate clinical management can be
      avoided while the need for liver biopsies can be reduced.

PMID- 23555579
TI  - Sputum IgE and cytokines in asthma: relationship with sputum cellular profile.
AB  - BACKGROUND: Local IgE production may play a role in asthma pathogenesis. The aim
      of the study was to assess sputum total IgE and cytokines in asthmatics according
      to sputum cellular phenotype. METHODS: We studied 122 subjects including 22 non
      atopic healthy subjects, 41 eosinophilic (sputum eosinophils >=3%), 16
      neutrophilic (sputum neutrophils >76%) and 43 pauci-granulocytic asthmatics
      (sputum eosinophils <3% and sputum neutrophils <=76%) recruited from the asthma
      clinic at CHU Liege. Sputum supernatant total IgE (tIgE) was measured by
      ImmunoCAP and sputum supernatant cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, IL
      17, IFN-gamma and TNF-alpha) were measured with the Luminex xMAP Technology by
      using commercially available Fluorokine MAP kits. RESULTS: After concentrating
      sputum samples, total IgE was detectable in the majority of subjects. Sputum IgE
      was raised in asthmatics when compared to healthy subjects. Overall, asthmatics
      did not significantly differ from healthy subjects with respect to cytokine
      levels. The eosinophilic asthma phenotype, however, was characterised by raised
      sputum tIgE, IL-5 and IL-13 compared to healthy subjects (p<0.001, p<0.001 and
      p<0.05 respectively) and pauci-granulocytic asthma (p<0.01, p<0.001 and p<0.05
      respectively) and raised IL-5 compared to neutrophilic asthma (p<0.01). When
      patients were classified according to sputum IgE levels, it appeared that IL-5,
      IL-6, IL-17 and TNF-alpha sputum supernatant levels were raised in the "IgE high"
      asthmatics (IgE >=0.1 kU/l) when compared to "IgE low" asthmatics (IgE<0.1 kU/l).
      CONCLUSION: The eosinophilic asthma phenotype was associated with raised sputum
      IgE and a Th2 cytokine profile. Raised sputum IgE was associated with a
      heterogeneous cytokine overproduction.

PMID- 23555581
TI  - The critical role of supervision in retaining staff in obstetric services: a
      three country study.
AB  - Millennium Development Goal (MDG) 5 commits us to reducing maternal mortality
      rates by three quarters and MDG 4 commits us to reducing child mortality by two
      thirds between 1990 and 2015. In order to reach these goals, greater access to
      basic emergency obstetric care (EmOC) as well as comprehensive EmOC which
      includes safe Caesarean section, is needed.. The limited capacity of health
      systems to meet demand for obstetric services has led several countries to
      utilize mid-level cadres as a substitute to more extensively trained and more
      internationally mobile healthcare workers. Although this does provide greater
      capacity for service delivery, concern about the performance and motivation of
      these workers is emerging. We propose that poor leadership characterized by
      inadequate and unstructured supervision underlies much of the dissatisfaction and
      turnover that has been shown to exist amongst these mid-level healthcare workers
      and indeed health workers more generally. To investigate this, we conducted a
      large-scale survey of 1,561 mid-level cadre healthcare workers (health workers
      trained for shorter periods to perform specific tasks e.g. clinical officers)
      delivering obstetric care in Malawi, Tanzania, and Mozambique. Participants
      indicated the primary supervision method used in their facility and we assessed
      their job satisfaction and intentions to leave their current workplace. In all
      three countries we found robust evidence indicating that a formal supervision
      process predicted high levels of job satisfaction and low intentions to leave. We
      find no evidence that facility level factors modify the link between supervisory
      methods and key outcomes. We interpret this evidence as strongly supporting the
      need to strengthen leadership and implement a framework and mechanism for
      systematic supportive supervision. This will promote better job satisfaction and
      improve the retention and performance of obstetric care workers, something which
      has the potential to improve maternal and neonatal outcomes in the countdown to
      2015.

PMID- 23555580
TI  - Multiple hits for the association of uterine fibroids on human chromosome 1q43.
AB  - Uterine leiomyomas (or fibroids) are the most common tumors in women of
      reproductive age. Early studies of two familial cancer syndromes, the multiple
      cutaneous and uterine leiomyomatosis (MCUL1), and the hereditary leiomyomatosis
      and renal cell cancer (HLRCC), implicated FH, a gene on chromosome 1q43 encoding
      the tricarboxylic acid cycle fumarate hydratase enzyme. The role of this
      metabolic housekeeping gene in tumorigenesis is still a matter of debate and
      pseudo-hypoxia has been suggested as a pathological mechanism. Inactivating FH
      mutations have rarely been observed in the nonsyndromic and common form of
      fibroids; however, loss of heterozygosity across FH appeared as a significant
      event in the pathogenesis of a subset of these tumors. To assess the role of FH
      and the linked genes in nonsyndromic uterine fibroids, we explored a two-megabase
      interval spanning FH in the NIEHS Uterine fibroid study, a cross-sectional study
      of fibroids in 1152 premenopausal women. Association mapping with a dense set of
      single nucleotide polymorphisms revealed several peaks of association (p = 10(-2)
      8.10(-5)) with the risk and/or growth of fibroids. In particular, genes encoding
      factors suspected (cytosolic FH) or known (EXO1 - exonuclease 1) to be involved
      in DNA mismatch repair emerged as candidate susceptibility genes whereas those
      acting in the autophagy/apoptosis (MAP1LC3C - microtubule-associated protein) or
      signal transduction (RGS7 - Regulator of G-protein and PLD5- Phospoholipase D)
      appeared to affect tumor growth. Furthermore, body mass index, a suspected
      confounder altered significantly but unpredictably the association with the
      candidate genes in the African and European American populations, suggesting the
      presence of a major obesity gene in the studied region. With the high potential
      for occult tumors in common conditions such as fibroids, validation of our data
      in family-based studies is needed.

PMID- 23555582
TI  - Endometrial receptivity: a revisit to functional genomics studies on human
      endometrium and creation of HGEx-ERdb.
AB  - BACKGROUND: Endometrium acquires structural and functional competence for embryo
      implantation only during the receptive phase of menstrual cycle in fertile women.
      Sizeable data are available to indicate that this ability is acquired by
      modulation in the expression of several genes/gene products. However, there
      exists little consensus on the identity, number of expressed/not-detected genes
      and their pattern of expression (up or down regulation). METHODS: Literature
      search was carried out to retrieve the data on endometrial expression of
      genes/proteins in various conditions. Data were compiled to generate a
      comprehensive database, Human Gene Expression Endometrial Receptivity database
      (HGEx-ERdb). The database was used to identify the Receptivity Associated Genes
      (RAGs) which display the similar pattern of expression across different
      investigations. Transcript levels of select RAGs encoding cell adhesion proteins
      were compared between two human endometrial epithelial cell lines; RL95-2 and HEC
      1-A by quantitative real time polymerase chain reaction (q-RT-PCR). Further
      select RAGs were investigated for their expression in pre-receptive (n = 4) and
      receptive phase (n = 4) human endometrial tissues by immunohistochemical studies.
      JAr spheroid attachment assays were carried out to assess the functional
      significance of two RAGs. RESULTS: HGEx-ERdb (http://resource.ibab.ac.in/HGEx
      ERdb/) helped identification of 179 RAGs, of which 151 genes were consistently
      expressed and upregulated and 28 consistently not-detected and downregulated in
      receptive phase as compared to pre-receptive phase. q-RT-PCR confirmed
      significantly higher (p<0.005) expression of Thrombospondin1 (THBS1), CD36 and
      Mucin 16 transcripts, in RL95-2 as compared to HEC-1-A. Further, the pretreatment
      with antibodies against CD36 and COMP led to a reduction in the percentage of JAr
      spheroids attached to RL95-2. Immunohistochemical studies demonstrated
      significantly higher (p<0.05) expression of endometrial THBS1, Cartilage
      Oligomeric Matrix Protein (COMP) and CD36 in the receptive phase as compared to
      pre-receptive phase human endometrial tissues. CONCLUSION: HGEx-ERdb is a
      catalogue of 19,285 genes, reported for their expression in human endometrium.
      Further 179 genes were identified as the RAGs. Expression analysis of some RAGs
      validated the utility of approach employed in creation of HGEx-ERdb. Studies
      aimed towards defining the specific functions of RAGs and their potential
      networks may yield relevant information about the major 'nodes' which regulate
      endometrial receptivity.

PMID- 23555583
TI  - Chemotherapy plus best supportive care versus best supportive care in patients
      with non-small cell lung cancer: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The use of chemotherapy has been proposed to increase the
      effectiveness of best supportive care (BSC) in patients with non-small cell lung
      cancer (NSCLC). Previous trials reported inconsistent findings regarding the
      efficacy and safety of chemotherapy on overall survival (OS) and treatment
      related mortality. We performed a systematic review and meta-analysis to evaluate
      the effects of chemotherapy plus BSC versus BSC alone on survival of patients
      with NSCLC. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched
      PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for
      relevant literature. All eligible studies included patients with NSCLC who had
      received chemotherapy and BSC or BSC alone. All eligible studies measured at
      least 1 of the following outcomes: OS or treatment-related mortality. Overall,
      patients that received chemotherapy plus BSC had significant longer OS than those
      that received BSC alone (HR, 0.76; 95%CI, 0.69-0.84; P<0.001). Additionally,
      chemotherapy plus BSC as compared to BSC alone resulted in a 28% RR reduction
      (95%CI: 12-40; P = 0.001) in 6-month mortality, 11% RR reduction (95%CI: 8-15;
      P<0.001) in 12-month mortality, and 5% RR reduction (95%CI: 1-8; P = 0.02) in 2
      year mortality. Toxicity was greater in patients that received chemotherapy plus
      BSC. CONCLUSION/SIGNIFICANCE: Chemotherapy plus BSC increased the OS and reduced
      the 6-month, 12-month, and 2-year mortality of NSCLC patients.

PMID- 23555585
TI  - How the spatial position of individuals affects their influence on swarms: a
      numerical comparison of two popular swarm dynamics models.
AB  - Schools of fish and flocks of birds are examples of self-organized animal groups
      that arise through social interactions among individuals. We numerically study
      two individual-based models, which recent empirical studies have suggested to
      explain self-organized group animal behavior: (i) a zone-based model where the
      group communication topology is determined by finite interacting zones of
      repulsion, attraction, and orientation among individuals; and (ii) a model where
      the communication topology is described by Delaunay triangulation, which is
      defined by each individual's Voronoi neighbors. The models include a tunable
      parameter that controls an individual's relative weighting of attraction and
      alignment. We perform computational experiments to investigate how effectively
      simulated groups transfer information in the form of velocity when an individual
      is perturbed. A cross-correlation function is used to measure the sensitivity of
      groups to sudden perturbations in the heading of individual members. The results
      show how relative weighting of attraction and alignment, location of the
      perturbed individual, population size, and the communication topology affect
      group structure and response to perturbation. We find that in the Delaunay-based
      model an individual who is perturbed is capable of triggering a cascade of
      responses, ultimately leading to the group changing direction. This phenomenon
      has been seen in self-organized animal groups in both experiments and nature.

PMID- 23555584
TI  - Association analysis of dyslipidemia-related genes in diabetic nephropathy.
AB  - Type 1 diabetes (T1D) increases risk of the development of microvascular
      complications and cardiovascular disease (CVD). Dyslipidemia is a common risk
      factor in the pathogenesis of both CVD and diabetic nephropathy (DN), with CVD
      identified as the primary cause of death in patients with DN. In light of this
      commonality, we assessed single nucleotide polymorphisms (SNPs) in thirty-seven
      key genetic loci previously associated with dyslipidemia in a T1D cohort using a
      case-control design. SNPs (n = 53) were genotyped using Sequenom in 1467
      individuals with T1D (718 cases with proteinuric nephropathy and 749 controls
      without nephropathy i.e. normal albumin excretion). Cases and controls were white
      and recruited from the UK and Ireland. Association analyses were performed using
      PLINK to compare allele frequencies in cases and controls. In a sensitivity
      analysis, samples from control individuals with reduced renal function (estimated
      glomerular filtration rate<60 ml/min/1.73 m(2)) were excluded. Correction for
      multiple testing was performed by permutation testing. A total of 1394 samples
      passed quality control filters. Following regression analysis adjusted by
      collection center, gender, duration of diabetes, and average HbA1c, two SNPs were
      significantly associated with DN. rs4420638 in the APOC1 region (odds ratio [OR]
      = 1.51; confidence intervals [CI]: 1.19-1.91; P = 0.001) and rs1532624 in CETP
      (OR = 0.82; CI: 0.69-0.99; P = 0.034); rs4420638 was also significantly
      associated in a sensitivity analysis (P = 0.016) together with rs7679 (P =
      0.027). However, no association was significant following correction for multiple
      testing. Subgroup analysis of end-stage renal disease status failed to reveal any
      association. Our results suggest common variants associated with dyslipidemia are
      not strongly associated with DN in T1D among white individuals. Our findings,
      cannot entirely exclude these key genes which are central to the process of
      dyslipidemia, from involvement in DN pathogenesis as our study had limited power
      to detect variants of small effect size. Analysis in larger independent cohorts
      is required.

PMID- 23555586
TI  - Human female genital tract infection by the obligate intracellular bacterium
      Chlamydia trachomatis elicits robust Type 2 immunity.
AB  - While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms
      that regulate host response to this intracellular Gram-negative bacterium remain
      undefined. This investigation thus used peripheral blood mononuclear cells and
      endometrial tissue from women with or without Chlamydia genital tract infection
      to better define this response. Initial genome-wide microarray analysis revealed
      highly elevated expression of matrix metalloproteinase 10 and other molecules
      characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia
      infected tissue. This result was corroborated in flow cytometry and
      immunohistochemistry studies that showed extant upper genital tract Chlamydia
      infection was associated with increased co-expression of CD200 receptor and CD206
      (markers of alternative macrophage activation) by endometrial macrophages as well
      as increased expression of GATA-3 (the transcription factor regulating TH2
      differentiation) by endometrial CD4(+) T cells. Also among women with genital
      tract Chlamydia infection, peripheral CD3(+) CD4(+) and CD3(+) CD4(-) cells that
      proliferated in response to ex vivo stimulation with inactivated chlamydial
      antigen secreted significantly more interleukin (IL)-4 than tumor necrosis
      factor, interferon-gamma, or IL-17; findings that repeated in T cells isolated
      from these same women 1 and 4 months after infection had been eradicated. Our
      results thus newly reveal that genital infection by an obligate intracellular
      bacterium induces polarization towards Type 2 immunity, including Chlamydia
      specific TH2 development. Based on these findings, we now speculate that Type 2
      immunity was selected by evolution as the host response to C. trachomatis in the
      human female genital tract to control infection and minimize immunopathological
      damage to vital reproductive structures.

PMID- 23555587
TI  - Pathways of economic inequalities in maternal and child health in urban India: a
      decomposition analysis.
AB  - BACKGROUND/OBJECTIVE: Children and women comprise vulnerable populations in terms
      of health and are gravely affected by the impact of economic inequalities through
      multi-dimensional channels. Urban areas are believed to have better socioeconomic
      and maternal and child health indicators than rural areas. This perception leads
      to the implementation of health policies ignorant of intra-urban health
      inequalities. Therefore, the objective of this study is to explain the pathways
      of economic inequalities in maternal and child health indicators among the urban
      population of India. METHODS: Using data from the third wave of the National
      Family Health Survey (NFHS, 2005-06), this study calculated relative contribution
      of socioeconomic factors to inequalities in key maternal and child health
      indicators such as antenatal check-ups (ANCs), institutional deliveries,
      proportion of children with complete immunization, proportion of underweight
      children, and Infant Mortality Rate (IMR). Along with regular CI estimates, this
      study applied widely used regression-based Inequality Decomposition model
      proposed by Wagstaff and colleagues. RESULTS: The CI estimates show considerable
      economic inequalities in women with less than 3 ANCs (CI = -0.3501),
      institutional delivery (CI = -0.3214), children without fully immunization (CI = 
      0.18340), underweight children (CI = -0.19420), and infant deaths (CI = 
      0.15596). Results of the decomposition model reveal that illiteracy among women
      and her partner, poor economic status, and mass media exposure are the critical
      factors contributing to economic inequalities in maternal and child health
      indicators. The residuals in all the decomposition models are very less; this
      implies that the above mentioned factors explained maximum inequalities in
      maternal and child health of urban population in India. CONCLUSION: Findings
      suggest that illiteracy among women and her partner, poor economic status, and
      mass media exposure are the critical pathways through which economic factors
      operate on inequalities in maternal and child health outcomes in urban India.

PMID- 23555588
TI  - Good exemplars of natural scene categories elicit clearer patterns than bad
      exemplars but not greater BOLD activity.
AB  - Within the range of images that we might categorize as a "beach", for example,
      some will be more representative of that category than others. Here we first
      confirmed that humans could categorize "good" exemplars better than "bad"
      exemplars of six scene categories and then explored whether brain regions
      previously implicated in natural scene categorization showed a similar
      sensitivity to how well an image exemplifies a category. In a behavioral
      experiment participants were more accurate and faster at categorizing good than
      bad exemplars of natural scenes. In an fMRI experiment participants passively
      viewed blocks of good or bad exemplars from the same six categories. A multi
      voxel pattern classifier trained to discriminate among category blocks showed
      higher decoding accuracy for good than bad exemplars in the PPA, RSC and V1. This
      difference in decoding accuracy cannot be explained by differences in overall
      BOLD signal, as average BOLD activity was either equivalent or higher for bad
      than good scenes in these areas. These results provide further evidence that V1,
      RSC and the PPA not only contain information relevant for natural scene
      categorization, but their activity patterns mirror the fundamentally graded
      nature of human categories. Analysis of the image statistics of our good and bad
      exemplars shows that variability in low-level features and image structure is
      higher among bad than good exemplars. A simulation of our neuroimaging experiment
      suggests that such a difference in variance could account for the observed
      differences in decoding accuracy. These results are consistent with both low
      level models of scene categorization and models that build categories around a
      prototype.

PMID- 23555589
TI  - Natalizumab treatment reduces fatigue in multiple sclerosis. Results from the
      TYNERGY trial; a study in the real life setting.
AB  - Fatigue is a significant symptom in multiple sclerosis (MS) patients. First
      generation disease modifying therapies (DMTs) are at best moderately effective to
      improve fatigue. Observations from small cohorts have indicated that natalizumab,
      an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study
      aimed to further evaluate the effects of natalizumab treatment on MS-related
      fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab
      was prescribed in a real-life setting, and a validated questionnaire, the Fatigue
      Scale for Motor and Cognitive functions (FSMC), was used both before and after 12
      months of treatment to evaluate a possible change in the fatigue experienced by
      the patients. In the treated cohort all measured variables, that is, fatigue
      score, quality of life, sleepiness, depression, cognition, and disability
      progression were improved from baseline (all p values<0.0001). Walking speed as
      measured by the six-minute walk-test also increased at month 12 (p = 0.0016). All
      patients were aware of the nature of the treatment agent, and of the study
      outcomes. CONCLUSION: Natalizumab, as used in a real-life setting, might improve
      MS-related fatigue based on the results from this one-armed un-controlled stud.
      Also other parameters related to patients' quality of life seemed to improve with
      natalizumab treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT00884481.

PMID- 23555590
TI  - Measuring health system strengthening: application of the balanced scorecard
      approach to rank the baseline performance of three rural districts in Zambia.
AB  - INTRODUCTION: There is growing interest in health system performance and recently
      WHO launched a report on health systems strengthening emphasising the need for
      close monitoring using system-wide approaches. One recent method is the balanced
      scorecard system. There is limited application of this method in middle- and low
      income countries. This paper applies the concept of balanced scorecard to
      describe the baseline status of three intervention districts in Zambia.
      METHODOLOGY: The Better Health Outcome through Mentoring and Assessment (BHOMA)
      project is a randomised step-wedged community intervention that aims to
      strengthen the health system in three districts in the Republic of Zambia. To
      assess the baseline status of the participating districts we used a modified
      balanced scorecard approach following the domains highlighted in the MOH 2011
      Strategic Plan. RESULTS: Differences in performance were noted by district and
      residence. Finance and service delivery domains performed poorly in all study
      districts. The proportion of the health workers receiving training in the past 12
      months was lowest in Kafue (58%) and highest in Luangwa district (77%). Under
      service capacity, basic equipment and laboratory capacity scores showed major
      variation, with Kafue and Luangwa having lower scores when compared to Chongwe.
      The finance domain showed that Kafue and Chongwe had lower scores (44% and 47%
      respectively). Regression model showed that children's clinical observation
      scores were negatively correlated with drug availability (coeff -0.40, p = 0.02).
      Adult clinical observation scores were positively association with adult service
      satisfaction score (coeff 0.82, p = 0.04) and service readiness (coeff 0.54, p =
      0.03). CONCLUSION: The study applied the balanced scorecard to describe the
      baseline status of 42 health facilities in three districts of Zambia. Differences
      in performance were noted by district and residence in most domains with finance
      and service delivery performing poorly in all study districts. This tool could be
      valuable in monitoring and evaluation of health systems.

PMID- 23555592
TI  - Population-based study of birth prevalence and factors associated with cleft lip
      and/or palate in Taiwan 2002-2009.
AB  - BACKGROUND: Facial cleft deformities, including cleft lip with or without cleft
      palate (CL/P) and cleft palate (CP), are common congenital birth anomalies,
      especially in Asia. This study aimed to analyze the prevalence of CL/P and CP and
      to identify associated factors in Taiwan. METHODS: This population-based
      epidemiological study retrospectively analyzed birth data obtained from the
      Department of Health in Taiwan for years 2002-2009. Frequency distribution,
      percentages and related predictors were investigated, and findings were presented
      by types of cleft deformities. Logistic regression analysis was performed to
      identify factors associated with cleft deformities. RESULTS: Overall prevalence
      of cleft deformities among 1,705,192 births was 0.1% for CL/P and 0.04% for CP
      over the 8-year study period. Higher prevalence of CL/P or CP was observed with
      multiple pregnancies, being male for CL/P, being female for CP, gestational age
      <=37 weeks and lower birth weight (<1.5 kg). Both CL/P and CP were significantly
      associated with gestational age <37 weeks and birth weight<1.5 kg (all P
      <0.0001). CL/P was significantly associated with multiple parities (P = 0.0004
      0.002). Male newborns and female newborns were significantly associated with CL/P
      and CP, respectively (both P<0.0001). CONCLUSIONS: Overall prevalence for
      congenital cleft deformities in study subjects was 0.1%, in keeping with high
      rates in Asia. Results suggest the need for awareness and early identification of
      those at high risk for cleft deformities, including newborns with gestational age
      <37 weeks, weighing <1.5 kg at birth and women with multiple parities, as a
      potential strategy to counter long-term adverse effects on speech and language in
      this population.

PMID- 23555591
TI  - Identification of telomerase RNAs from filamentous fungi reveals conservation
      with vertebrates and yeasts.
AB  - Telomeres are the nucleoprotein complexes at eukaryotic chromosomal ends.
      Telomeric DNA is synthesized by the ribonucleoprotein telomerase, which comprises
      a telomerase reverse transcriptase (TERT) and a telomerase RNA (TER). TER
      contains a template for telomeric DNA synthesis. Filamentous fungi possess
      extremely short and tightly regulated telomeres. Although TERT is well conserved
      between most organisms, TER is highly divergent and thus difficult to identify.
      In order to identify the TER sequence, we used the unusually long telomeric
      repeat sequence of Aspergillus oryzae together with reverse-transcription-PCR and
      identified a transcribed sequence that contains the potential template within a
      region predicted to be single stranded. We report the discovery of TERs from
      twelve other related filamentous fungi using comparative genomic analysis. These
      TERs exhibited strong conservation with the vertebrate template sequence, and two
      of these potentially use the identical template as humans. We demonstrate the
      existence of important processing elements required for the maturation of yeast
      TERs such as an Sm site, a 5' splice site and a branch point, within the newly
      identified TER sequences. RNA folding programs applied to the TER sequences show
      the presence of secondary structures necessary for telomerase activity, such as a
      yeast-like template boundary, pseudoknot, and a vertebrate-like three-way
      junction. These telomerase RNAs identified from filamentous fungi display
      conserved structural elements from both yeast and vertebrate TERs. These findings
      not only provide insights into the structure and evolution of a complex RNA but
      also provide molecular tools to further study telomere dynamics in filamentous
      fungi.

PMID- 23555593
TI  - Treatment success in cancer: industry compared to publicly sponsored randomized
      controlled trials.
AB  - OBJECTIVE: To assess if commercially sponsored trials are associated with higher
      success rates than publicly-sponsored trials. STUDY DESIGN AND SETTINGS: We
      undertook a systematic review of all consecutive, published and unpublished phase
      III cancer randomized controlled trials (RCTs) conducted by GlaxoSmithKline (GSK)
      and the NCIC Clinical Trials Group (CTG). We included all phase III cancer RCTs
      assessing treatment superiority from 1980 to 2010. Three metrics were assessed to
      determine treatment successes: (1) the proportion of statistically significant
      trials favouring the experimental treatment, (2) the proportion of the trials in
      which new treatments were considered superior according to the investigators, and
      (3) quantitative synthesis of data for primary outcomes as defined in each trial.
      RESULTS: GSK conducted 40 cancer RCTs accruing 19,889 patients and CTG conducted
      77 trials enrolling 33,260 patients. 42% (99%CI 24 to 60) of the results were
      statistically significant favouring experimental treatments in GSK compared to
      25% (99%CI 13 to 37) in the CTG cohort (RR = 1.68; p = 0.04). Investigators
      concluded that new treatments were superior to standard treatments in 80% of GSK
      compared to 44% of CTG trials (RR = 1.81; p<0.001). Meta-analysis of the primary
      outcome indicated larger effects in GSK trials (odds ratio = 0.61 [99%CI 0.47
      0.78] compared to 0.86 [0.74-1.00]; p = 0.003). However, testing for the effect
      of treatment over time indicated that treatment success has become comparable in
      the last decade. CONCLUSIONS: While overall industry sponsorship is associated
      with higher success rates than publicly-sponsored trials, the difference seems to
      have disappeared over time.

PMID- 23555594
TI  - The effect of group attachment and social position on prosocial behavior.
      Evidence from lab-in-the-field experiments.
AB  - Social life is regulated by norms of fairness that constrain selfish behavior.
      While a substantial body of scholarship on prosocial behavior has provided
      evidence of such norms, large inter- and intra-personal variation in prosocial
      behavior still needs to be explained. The article identifies two social
      structural dimensions along which people's generosity varies systematically:
      group attachment and social position. We conducted lab-in-the-field experiments
      involving 2,597 members of producer organizations in rural Uganda. Using
      different variants of the dictator game, we demonstrate that group attachment
      positively affects prosocial behavior, and that this effect is not simply the by
      product of the degree of proximity between individuals. Second, we show that
      occupying a formal position in an organization or community leads to greater
      generosity toward in-group members. Taken together, our findings show that
      prosocial behavior is not an invariant social trait; rather, it varies according
      to individuals' relative position in the social structure.

PMID- 23555595
TI  - A new method for the discovery of essential proteins.
AB  - BACKGROUND: Experimental methods for the identification of essential proteins are
      always costly, time-consuming, and laborious. It is a challenging task to find
      protein essentiality only through experiments. With the development of high
      throughput technologies, a vast amount of protein-protein interactions are
      available, which enable the identification of essential proteins from the network
      level. Many computational methods for such task have been proposed based on the
      topological properties of protein-protein interaction (PPI) networks. However,
      the currently available PPI networks for each species are not complete, i.e.
      false negatives, and very noisy, i.e. high false positives, network topology
      based centrality measures are often very sensitive to such noise. Therefore,
      exploring robust methods for identifying essential proteins would be of great
      value. METHOD: In this paper, a new essential protein discovery method, named
      CoEWC (Co-Expression Weighted by Clustering coefficient), has been proposed.
      CoEWC is based on the integration of the topological properties of PPI network
      and the co-expression of interacting proteins. The aim of CoEWC is to capture the
      common features of essential proteins in both date hubs and party hubs. The
      performance of CoEWC is validated based on the PPI network of Saccharomyces
      cerevisiae. Experimental results show that CoEWC significantly outperforms the
      classical centrality measures, and that it also outperforms PeC, a newly proposed
      essential protein discovery method which outperforms 15 other centrality measures
      on the PPI network of Saccharomyces cerevisiae. Especially, when predicting no
      more than 500 proteins, even more than 50% improvements are obtained by CoEWC
      over degree centrality (DC), a better centrality measure for identifying protein
      essentiality. CONCLUSIONS: We demonstrate that more robust essential protein
      discovery method can be developed by integrating the topological properties of
      PPI network and the co-expression of interacting proteins. The proposed
      centrality measure, CoEWC, is effective for the discovery of essential proteins.

PMID- 23555597
TI  - Recruitment constraints in Singapore's fluted giant clam (Tridacna squamosa)
      population--a dispersal model approach.
AB  - Recruitment constraints on Singapore's dwindling fluted giant clam, Tridacna
      squamosa, population were studied by modelling fertilisation, larval transport,
      and settlement using real-time hydrodynamic forcing combined with knowledge of
      spawning characteristics, larval development, behaviour, and settlement cues.
      Larval transport was simulated using a finite-volume advection-diffusion model
      coupled to a three-dimensional hydrodynamic model. Three recruitment constraint
      hypotheses were tested: 1) there is limited connectivity between Singapore's
      reefs and other reefs in the region, 2) there is limited exchange within
      Singapore's Southern Islands, and 3) there exist low-density constraints to
      fertilisation efficacy (component Allee effects). Results showed that
      connectivity among giant clam populations was primarily determined by residual
      hydrodynamic flows and spawning time, with greatest chances of successful
      settlement occurring when spawning and subsequent larval dispersal coincided with
      the period of lowest residual flow. Simulations suggested poor larval transport
      from reefs located along the Peninsular Malaysia to Singapore, probably due to
      strong surface currents between the Andaman Sea and South China Sea combined with
      a major land barrier disrupting larval movement among reefs. The model, however,
      predicted offshore coral reefs to the southeast of Singapore (Bintan and Batam)
      may represent a significant source of larvae. Larval exchange within Singapore's
      Southern Islands varied substantially depending on the locations of source and
      sink reefs as well as spawning time; but all simulations resulted in low settler
      densities (2.1-68.6 settled individuals per 10,000 m(2)). Poor fertilisation
      rates predicted by the model indicate that the low density and scattered
      distribution of the remaining T. squamosa in Singapore are likely to
      significantly inhibit any natural recovery of local stocks.

PMID- 23555596
TI  - Development of strategies for SNP detection in RNA-seq data: application to
      lymphoblastoid cell lines and evaluation using 1000 Genomes data.
AB  - Next-generation RNA sequencing (RNA-seq) maps and analyzes transcriptomes and
      generates data on sequence variation in expressed genes. There are few reported
      studies on analysis strategies to maximize the yield of quality RNA-seq SNP data.
      We evaluated the performance of different SNP-calling methods following alignment
      to both genome and transcriptome by applying them to RNA-seq data from a HapMap
      lymphoblastoid cell line sample and comparing results with sequence variation
      data from 1000 Genomes. We determined that the best method to achieve high
      specificity and sensitivity, and greatest number of SNP calls, is to remove
      duplicate sequence reads after alignment to the genome and to call SNPs using
      SAMtools. The accuracy of SNP calls is dependent on sequence coverage available.
      In terms of specificity, 89% of RNA-seq SNPs calls were true variants where
      coverage is >10X. In terms of sensitivity, at >10X coverage 92% of all expected
      SNPs in expressed exons could be detected. Overall, the results indicate that RNA
      seq SNP data are a very useful by-product of sequence-based transcriptome
      analysis. If RNA-seq is applied to disease tissue samples and assuming that genes
      carrying mutations relevant to disease biology are being expressed, a very high
      proportion of these mutations can be detected.

PMID- 23555598
TI  - Light-induced translocation of RGS9-1 and Gbeta5L in mouse rod photoreceptors.
AB  - The transducin GTPase-accelerating protein complex, which determines the
      photoresponse duration of photoreceptors, is composed of RGS9-1, Gbeta5L and
      R9AP. Here we report that RGS9-1 and Gbeta5L change their distribution in rods
      during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gbeta5L
      are primarily located in rod inner segments. But very dim-light exposure quickly
      translocates them to the outer segments. In contrast, their anchor protein R9AP
      remains in the outer segment at all times. In the dark, Gbeta5L's interaction
      with R9AP decreases significantly and RGS9-1 is phosphorylated at S(475) to a
      significant degree. Dim light exposure leads to quick de-phosphorylation of RGS9
      1. Furthermore, after prolonged dark adaptation, RGS9-1 and transducin Galpha are
      located in different cellular compartments. These results suggest a previously
      unappreciated mechanism by which prolonged dark adaptation leads to increased
      light sensitivity in rods by dissociating RGS9-1 from R9AP and redistributing it
      to rod inner segments.

PMID- 23555599
TI  - The p14ARF alternate reading frame protein enhances DNA binding of topoisomerase
      I by interacting with the serine 506-phosphorylated core domain.
AB  - In addition to its well-characterized function as a tumor suppressor, p14ARF
      (ARF) is a positive regulator of topoisomerase I (topo I), a central enzyme in
      DNA metabolism and a target for cancer therapy. We previously showed that topo I
      hyperphosphorylation, a cancer-associated event mediated by elevated levels of
      the protein kinase CK2, increases topo I activity and the cellular sensitivity to
      topo I-targeted drugs. Topo I hyperphosphorylation also increases its interaction
      with ARF. Because the ARF-topo I interaction could be highly relevant to DNA
      metabolism and cancer treatment, we identified the regions of topo I involved in
      ARF binding and characterized the effects of ARF binding on topo I function.
      Using a series of topo I deletion constructs, we found that ARF interacted with
      the topo I core domain, which encompasses most of the catalytic and DNA
      interacting residues. ARF binding increased the DNA relaxation activity of
      hyperphosphorylated topo I by enhancing its association with DNA, but did not
      affect the topo I catalytic rate. In cells, ARF promoted the chromatin
      association of hyperphosphorylated, but not basal phosphorylated, topo I, and
      increased topo I-mediated DNA nicking under conditions of oxidative stress. The
      aberrant nicking was found to correlate with increased formation of DNA double
      strand breaks, which are precursors of many genome destabilizing events. The
      results suggest that the convergent actions of oxidative stress and elevated CK2
      and ARF levels, which are common features of cancer cells, lead to a
      dysregulation of topo I that may contribute both to the cellular response to topo
      I-targeted drugs and to genome instability.

PMID- 23555600
TI  - Crumbs affects protein dynamics in anterior regions of the developing Drosophila
      embryo.
AB  - Maintenance of apico-basal polarity is essential for epithelial integrity and
      requires particular reinforcement during tissue morphogenesis, when cells are
      reorganised, undergo shape changes and remodel their junctions. It is well
      established that epithelial integrity during morphogenetic processes depends on
      the dynamic exchange of adherens junction components, but our knowledge on the
      dynamics of other proteins and their dynamics during these processes is still
      limited. The early Drosophila embryo is an ideal system to study membrane
      dynamics during morphogenesis. Here, morphogenetic activities differ along the
      anterior-posterior axis, with the extending germband showing a high degree of
      epithelial remodelling. We developed a Fluorescence Recovery After Photobleaching
      (FRAP) assay with a higher temporal resolution, which allowed the distinction
      between a fast and a slow component of recovery of membrane proteins during the
      germband extension stage. We show for the first time that the recovery kinetics
      of a general membrane marker, SpiderGFP, differs in the anterior and posterior
      parts of the embryo, which correlates well with the different morphogenetic
      activities of the respective embryonic regions. Interestingly, absence of crumbs,
      a polarity regulator essential for epithelial integrity in the Drosophila embryo,
      decreases the fast component of SpiderGFP and of the apical marker Stranded at
      Second-Venus specifically in the anterior region. We suggest that the defects in
      kinetics observed in crumbs mutant embryos are the first signs of tissue
      instability in this region, explaining the earlier breakdown of the head
      epidermis in comparison to that of the trunk, and that diffusion in the plasma
      membrane is affected by the absence of Crumbs.

PMID- 23555601
TI  - Reciprocal allosteric modulation of carbon monoxide and warfarin binding to
      ferrous human serum heme-albumin.
AB  - Human serum albumin (HSA), the most abundant protein in human plasma, could be
      considered as a prototypic monomeric allosteric protein, since the ligand
      dependent conformational adaptability of HSA spreads beyond the immediate
      proximity of the binding site(s). As a matter of fact, HSA is a major transport
      protein in the bloodstream and the regulation of the functional allosteric
      interrelationships between the different binding sites represents a fundamental
      information for the knowledge of its transport function. Here, kinetics and
      thermodynamics of the allosteric modulation: (i) of carbon monoxide (CO) binding
      to ferrous human serum heme-albumin (HSA-heme-Fe(II)) by warfarin (WF), and (ii)
      of WF binding to HSA-heme-Fe(II) by CO are reported. All data were obtained at pH
      7.0 and 25 degrees C. Kinetics of CO and WF binding to the FA1 and FA7 sites of
      HSA-heme-Fe(II), respectively, follows a multi-exponential behavior (with the
      same relative percentage for the two ligands). This can be accounted for by the
      existence of multiple conformations and/or heme-protein axial coordination forms
      of HSA-heme-Fe(II). The HSA-heme-Fe(II) populations have been characterized by
      resonance Raman spectroscopy, indicating the coexistence of different species
      characterized by four-, five- and six-coordination of the heme-Fe atom. As a
      whole, these results suggest that: (i) upon CO binding a conformational change of
      HSA-heme-Fe(II) takes place (likely reflecting the displacement of an endogenous
      ligand by CO), and (ii) CO and/or WF binding brings about a ligand-dependent
      variation of the HSA-heme-Fe(II) population distribution of the various
      coordinating species. The detailed thermodynamic and kinetic analysis here
      reported allows a quantitative description of the mutual allosteric effect of CO
      and WF binding to HSA-heme-Fe(II).

PMID- 23555602
TI  - Mechanisms of team-sport-related brain injuries in children 5 to 19 years old:
      opportunities for prevention.
AB  - BACKGROUND: There is a gap in knowledge about the mechanisms of sports-related
      brain injuries. The objective of this study was to determine the mechanisms of
      brain injuries among children and youth participating in team sports. METHODS: We
      conducted a retrospective case series of brain injuries suffered by children
      participating in team sports. The Canadian Hospitals Injury Reporting and
      Prevention Program (CHIRPP) database was searched for brain injury cases among 5
      19 year-olds playing ice hockey, soccer, American football (football),
      basketball, baseball, or rugby between 1990 and 2009. Mechanisms of injury were
      classified as "struck by player," "struck by object," "struck by sport
      implement," "struck surface," and "other." A descriptive analysis was performed.
      RESULTS: There were 12,799 brain injuries related to six team sports (16.2% of
      all brain injuries registered in CHIRPP). Males represented 81% of injuries and
      the mean age was 13.2 years. Ice hockey accounted for the greatest number of
      brain injuries (44.3%), followed by soccer (19.0%) and football (12.9%). In ice
      hockey, rugby, and basketball, striking another player was the most common injury
      mechanism. Football, basketball, and soccer also demonstrated high proportions of
      injuries due to contact with an object (e.g., post) among younger players. In
      baseball, a common mechanism in the 5-9 year-old group was being hit with a bat
      as a result of standing too close to the batter (26.1% males, 28.3% females).
      INTERPRETATION: Many sports-related brain injury mechanisms are preventable. The
      results suggest that further efforts aimed at universal rule changes, safer
      playing environments, and the education of coaches, players, and parents should
      be targeted in maximizing prevention of sport-related brain injury using a
      multifaceted approach.

PMID- 23555604
TI  - Reconstruction of the abdominal vagus nerve using sural nerve grafts in canine
      models.
AB  - BACKGROUND: Recently, vagus nerve preservation or reconstruction of vagus has
      received increasing attention. The present study aimed to investigate the
      feasibility of reconstructing the severed vagal trunk using an autologous sural
      nerve graft. METHODS: Ten adult Beagle dogs were randomly assigned to two groups
      of five, the nerve grafting group (TG) and the vagal resection group (VG). The
      gastric secretion and emptying functions in both groups were assessed using
      Hollander insulin and acetaminophen tests before surgery and three months after
      surgery. All dogs underwent laparotomy under general anesthesia. In TG group,
      latency and conduction velocity of the action potential in a vagal trunk were
      measured, and then nerves of 4 cm long were cut from the abdominal anterior and
      posterior vagal trunks. Two segments of autologous sural nerve were collected for
      performing end-to-end anastomoses with the cut ends of vagal trunk (8-0 nylon
      suture, 3 sutures for each anastomosis). Dogs in VG group only underwent partial
      resections of the anterior and posterior vagal trunks. Laparotomy was performed
      in dogs of TG group, and latency and conduction velocity of the action potential
      in their vagal trunks were measured. The grafted nerve segment was removed, and
      stained with anti-neurofilament protein and toluidine blue. RESULTS: Latency of
      the action potential in the vagal trunk was longer after surgery than before
      surgery in TG group, while the conduction velocity was lower after surgery. The
      gastric secretion and emptying functions were weaker after surgery in dogs of
      both groups, but in TG group they were significantly better than in VG group.
      Anti-neurofilament protein staining and toluidine blue staining showed there were
      nerve fibers crossing the anastomosis of the vagus and sural nerves in dogs of TG
      group. CONCLUSION: Reconstruction of the vagus nerve using the sural nerve is
      technically feasible.

PMID- 23555603
TI  - A readily applicable strategy to convert peptides to peptoid-based therapeutics.
AB  - Incorporation of unnatural amino acids and peptidomimetic residues into
      therapeutic peptides is highly efficacious and commonly employed, but generally
      requires laborious trial-and-error approaches. Previously, we demonstrated that
      C20 peptide has the potential to be a potential antiviral agent. Herein we report
      our attempt to improve the biological properties of this peptide by introducing
      peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled
      with a competitive fluorescence polarization assay developed for identifying
      antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues
      within C20 peptide. The synergistic benefits of combining these (and other)
      commonly employed methods could lead to a easily applicable strategy for
      designing and refining therapeutically-attractive peptidomimetics.

PMID- 23555605
TI  - Hypersensitive detection and quantitation of BoNT/A by IgY antibody against
      substrate linear-peptide.
AB  - Botulinum neurotoxin A (BoNT/A), the most acutely poisonous substance to humans
      known, cleave its SNAP-25 substrate with high specificity. Based on the
      endopeptidase activity, different methods have been developed to detect BoNT/A,
      but most lack ideal reproducibility or sensitivity, or suffer from long-term or
      unwanted interferences. In this study, we developed a simple method to detect and
      quantitate trace amounts of botulinum neurotoxin A using the IgY antibody against
      a linear-peptide substrate. The effects of reaction buffer, time, and temperature
      were analyzed and optimized. When the optimized assay was used to detect BoNT/A,
      the limit of detection of the assay was 0.01 mouse LD50 (0.04 pg), and the limit
      of quantitation was 0.12 mouse LD50/ml (0.48 pg). The findings also showed
      favorable specificity of detecting BoNT/A. When used to detect BoNT/A in milk or
      human serum, the proposed assay exhibited good quantitative accuracy (88% <
      recovery < 111%; inter- and intra-assay CVs < 18%). This method of detection took
      less than 3 h to complete, indicating that it can be a valuable method of
      detecting BoNT/A in food or clinical diagnosis.

PMID- 23555606
TI  - Quantitative analysis of gender stereotypes and information aggregation in a
      national election.
AB  - By analyzing a database of a questionnaire answered by a large majority of
      candidates and elected in a parliamentary election, we quantitatively verify that
      (i) female candidates on average present political profiles which are more
      compassionate and more concerned with social welfare issues than male candidates
      and (ii) the voting procedure acts as a process of information aggregation. Our
      results show that information aggregation proceeds with at least two distinct
      paths. In the first case candidates characterize themselves with a political
      profile aiming to describe the profile of the majority of voters. This is
      typically the case of candidates of political parties which are competing for the
      center of the various political dimensions. In the second case, candidates choose
      a political profile manifesting a clear difference from opposite political
      profiles endorsed by candidates of a political party positioned at the opposite
      extreme of some political dimension.

PMID- 23555607
TI  - Effect of sharp jumps at the edges of phase response curves on synchronization of
      electrically coupled neuronal oscillators.
AB  - We study synchronization phenomenon of coupled neuronal oscillators using the
      theory of weakly coupled oscillators. The role of sudden jumps in the phase
      response curve profiles found in some experimental recordings and models on the
      ability of coupled neurons to exhibit synchronous and antisynchronous behavior is
      investigated, when the coupling between the neurons is electrical. The level of
      jumps in the phase response curve at either end, spike width and frequency of
      voltage time course of the coupled neurons are parameterized using piecewise
      linear functional forms, and the conditions for stable synchrony and stable
      antisynchrony in terms of those parameters are computed analytically. The role of
      the peak position of the phase response curve on phase-locking is also
      investigated.

PMID- 23555608
TI  - Sex-specific weight loss mediates sexual size dimorphism in Drosophila
      melanogaster.
AB  - The selective pressures leading to the evolution of Sexual Size Dimorphism (SSD)
      have been well studied in many organisms, yet, the underlying developmental
      mechanisms are poorly understood. By generating a complete growth profile by sex
      in Drosophila melanogaster, we describe the sex-specific pattern of growth
      responsible for SSD. Growth rate and critical size for pupariation significantly
      contributed to adult SSD, whereas duration of growth did not. Surprisingly, SSD
      at peak larval mass was twice that of the uneclosed adult SSD with weight loss
      between peak larval mass and pupariation playing an important role in generating
      the final SSD. Our finding that weight loss is an important regulator of SSD adds
      additional complexity to our understanding of how body size is regulated in
      different sexes. Collectively, these data allow for the elucidation of the
      molecular-genetic mechanisms that generate SSD, an important component of
      understanding how SSD evolves.

PMID- 23555609
TI  - Differential network analysis reveals genetic effects on catalepsy modules.
AB  - We performed short-term bi-directional selective breeding for haloperidol-induced
      catalepsy, starting from three mouse populations of increasingly complex genetic
      structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four
      inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred
      strain founders of the Collaborative Cross (CC). All three selections were
      successful, with large differences in haloperidol response emerging within three
      generations. Using a custom differential network analysis procedure, we found
      that gene coexpression patterns changed significantly; importantly, a number of
      these changes were concordant across genetic backgrounds. In contrast, absolute
      gene-expression changes were modest and not concordant across genetic
      backgrounds, in spite of the large and similar phenotypic differences. By
      inferring strain contributions from the parental lines, we are able to identify
      significant differences in allelic content between the selected lines concurrent
      with large changes in transcript connectivity. Importantly, this observation
      implies that genetic polymorphisms can affect transcript and module connectivity
      without large changes in absolute expression levels. We conclude that, in this
      case, selective breeding acts at the subnetwork level, with the same modules but
      not the same transcripts affected across the three selections.

PMID- 23555610
TI  - Iron and obesity status-associated insulin resistance influence circulating
      fibroblast-growth factor-23 concentrations.
AB  - Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and
      linked to metabolic risk. We aimed to explore circulating FGF-23 in association
      with fatness and insulin sensitivity, atherosclerosis and bone mineral density
      (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23)
      concentrations (ELISA) were measured in 133 middle aged men from the general
      population in association with insulin sensitivity (Cohort 1); and in association
      with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media
      thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort
      2). Circulating iFGF-23 was also measured before and after weight loss. In all
      subjects as a whole, serum intact and C-terminal concentrations were linearly and
      positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23
      concentrations increased with insulin resistance. Serum creatinine contributed to
      iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age
      or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF
      23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting
      and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively
      associated with circulating vitamin D and ferritin levels. The associations of
      CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no
      longer significant after controlling for BMI. Weight loss led to decreased iFGF
      23 concentrations. In summary, the associations of circulating FGF-23
      concentration with parameters of glucose metabolism, bone density and
      atherosclerosis are dependent on iron and obesity status-associated insulin
      resistance.

PMID- 23555612
TI  - Islands of conformational stability for filopodia.
AB  - Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly
      from a cell surface while remaining closed in a membrane tube. We study the
      subtle issue of the mechanical stability of such filopodia and how this depends
      on the deformation of the membrane that arises when the fiber bundle adopts a
      helical configuration. We calculate the ground state conformation of such
      filopodia, taking into account the steric interaction between the membrane and
      the enclosed semiflexible fiber bundle. For typical filopodia we find that a
      minimum number of fibers is required for filopodium stability. Our calculation
      elucidates how experimentally observed filopodia can obviate the classical Euler
      buckling condition and remain stable up to several tens of MUm. We briefly
      discuss how experimental observation of the results obtained in this work for the
      helical-like deformations of enclosing membrane tubes in filopodia could possibly
      be observed in the acrosomal reactions of the sea cucumber Thyone, and the
      horseshoe crab Limulus. Any realistic future theories for filopodium stability
      are likely to rely on an accurate treatment of such steric effects, as analysed
      in this work.

PMID- 23555611
TI  - Platelets recognize brain-specific glycolipid structures, respond to
      neurovascular damage and promote neuroinflammation.
AB  - Platelets respond to vascular damage and contribute to inflammation, but their
      role in the neurodegenerative diseases is unknown. We found that the systemic
      administration of brain lipid rafts induced a massive platelet activation and
      degranulation resulting in a life-threatening anaphylactic-like response in mice.
      Platelets were engaged by the sialated glycosphingolipids (gangliosides)
      integrated in the rigid structures of astroglial and neuronal lipid rafts. The
      brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the
      platelets and this recognition involved multiple receptors with P-selectin
      (CD62P) playing the central role. During the neuroinflammation, platelets
      accumulated in the central nervous system parenchyma, acquired an activated
      phenotype and secreted proinflammatory factors, thereby triggering immune
      response cascades. This study determines a new role of platelets which directly
      recognize a neuronal damage and communicate with the cells of the immune system
      in the pathogenesis of neurodegenerative diseases.

PMID- 23555614
TI  - Vitamin D deficiency in medical patients at a central hospital in Malawi: a
      comparison with TB patients from a previous study.
AB  - OBJECTIVES: To determine the prevalence of vitamin D deficiency (VDD) in adult
      medical, non-tuberculous (non-TB) patients. To investigate associations with VDD.
      To compare the results with a similar study in TB patients at the same hospital.
      DESIGN: Cross-sectional sample. SETTING: Central hospital in Malawi.
      PARTICIPANTS: Adult non-TB patients (n = 157), inpatients and outpatients.
      OUTCOME MEASURES: The primary outcome was the prevalence of VDD. Potentially
      causal associations sought included nutritional status, in/outpatient status, HIV
      status, anti-retroviral therapy (ART) and, by comparison with a previous study, a
      diagnosis of tuberculosis (TB). RESULTS: Hypovitaminosis D (<=75 nmol/L) occurred
      in 47.8% (75/157) of patients, 16.6% (26/157) of whom had VDD (<=50 nmol/L). None
      had severe VDD (<=25 nmol/L). VDD was found in 22.8% (23/101) of in-patients and
      5.4% (3/56) of out-patients. In univariable analysis in-patient status, ART use
      and low dietary vitamin D were significant predictors of VDD. VDD was less
      prevalent than in previously studied TB patients in the same hospital (68/161 =
      42%). In multivariate analysis of the combined data set from both studies, having
      TB (OR 3.61, 95%CI 2.02-6.43) and being an in-patient (OR 2.70, 95%CI 1.46-5.01)
      were significant independent predictors of VDD. CONCLUSIONS: About half of adult
      medical patients without TB have suboptimal vitamin D status, which is more
      common in in-patients. VDD is much more common in TB patients than non-TB
      patients, even when other variables are controlled for, suggesting that vitamin D
      deficiency is associated with TB.

PMID- 23555613
TI  - Scoring methods for building genotypic scores: an application to didanosine
      resistance in a large derivation set.
AB  - BACKGROUND: Several attempts have been made to determine HIV-1 resistance from
      genotype resistance testing. We compare scoring methods for building weighted
      genotyping scores and commonly used systems to determine whether the virus of a
      HIV-infected patient is resistant. METHODS AND PRINCIPAL FINDINGS: Three
      statistical methods (linear discriminant analysis, support vector machine and
      logistic regression) are used to determine the weight of mutations involved in
      HIV resistance. We compared these weighted scores with known interpretation
      systems (ANRS, REGA and Stanford HIV-db) to classify patients as resistant or
      not. Our methodology is illustrated on the Forum for Collaborative HIV Research
      didanosine database (N = 1453). The database was divided into four samples
      according to the country of enrolment (France, USA/Canada, Italy and
      Spain/UK/Switzerland). The total sample and the four country-based samples allow
      external validation (one sample is used to estimate a score and the other samples
      are used to validate it). We used the observed precision to compare the
      performance of newly derived scores with other interpretation systems. Our
      results show that newly derived scores performed better than or similar to
      existing interpretation systems, even with external validation sets. No
      difference was found between the three methods investigated. Our analysis
      identified four new mutations associated with didanosine resistance: D123S,
      Q207K, H208Y and K223Q. CONCLUSIONS: We explored the potential of three
      statistical methods to construct weighted scores for didanosine resistance. Our
      proposed scores performed at least as well as already existing interpretation
      systems and previously unrecognized didanosine-resistance associated mutations
      were identified. This approach could be used for building scores of genotypic
      resistance to other antiretroviral drugs.

PMID- 23555615
TI  - Silencing of RASSF3 by DNA hypermethylation is associated with tumorigenesis in
      somatotroph adenomas.
AB  - The pathogenic mechanisms underlying pituitary somatotroph adenoma formation,
      progression are poorly understood. To identify candidate tumor suppressor genes
      involved in pituitary somatotroph adenoma tumorigenesis, we used HG18 CpG plus
      Promoter Microarray in 27 human somatotroph adenomas and 4 normal human
      adenohypophyses. RASSF3 was found with frequent methylation of CpG island in its
      promoter region in somatotroph adenomas but rarely in adenohypophyses. This
      result was confirmed by pyrosequencing analysis. We also found that RASSF3 mRNA
      level correlated negatively to its gene promoter methylation level. RASSF3
      hypermethylation and downregulation was also observed in rat GH3 and mouse GT1.1
      somatotroph adenoma cell lines. 5-Aza-2' deoxycytidine and trichostatin-A
      treatment induced RASSF3 promoter demethylation, and restored its expression in
      GH3 and GT1.1 cell lines. RASSF3 overexpression in GH3 and GT1.1 cells inhibited
      proliferation, induced apoptosis accompanied by increased Bax, p53, and caspase-3
      protein and decreased Bcl-2 protein expression. We also found that the antitumor
      effect of RASSF3 was p53 dependent, and p53 knockdown blocked RASSF3-induced
      apoptosis and growth inhibition. Taken together, our results suggest that
      hypermethylation-induced RASSF3 silencing plays an important role in the
      tumorigenesis of pituitary somatotroph adenomas.

PMID- 23555616
TI  - Drug use and sex work: competing risk factors for newly acquired HIV in Yunnan,
      China.
AB  - OBJECTIVE: To investigate the HIV incidence and its related factors among female
      sex workers (FSWs) in a high prevalence area where injection drug use is also
      widely documented. METHOD: A cross-sectional study of 1642 female sex workers
      (FSWs) was conducted in Honghe Prefecture of Yunnan Province. Interviewed
      questionnaires were administrated to collect information on sexual partnerships,
      condom use and illicit drug using behaviors etc. Blood samples were collected to
      test for HIV antibodies, and all HIV seropositive specimens were tested with the
      BED IgG capture-based enzyme immunosorbent assay (BED-CEIA) to distinguish
      between new and established HIV infection (<153 days). RESULTS: 15.9% (261/1642)
      of participants reported ever having used drugs, and 7.4% had injected in recent
      3 months. The overall HIV prevalence was 10.2% (168/1642), among which 16.7%
      (28/168) were identified as recent infections using BED-CEIA. The crude HIV
      incidence estimated from BED-CEIA results was 4.4 (95%CI 2.8-6.0) /100 person
      years (PY). Multivariate logistic analysis showed that an illicit drug using
      history (by either self-reporting or urine opiates testing) was both significant
      risk factors both for HIV established and recent infection (each p<0.05). Drug
      using FSWs (DU-FSW) reported more male clients in the previous week, and had
      significantly higher prevalence of HIV, chlamydia trachomatis and HSV-2 as
      compared to non DU-FSW (each p<0.05). CONCLUSION: Our results show that a history
      of drug use poses significant risks for both new and established HIV infection
      among FSWs, and that HIV-incidence among Honghe FSWs is relatively high compared
      to similar populations. Comprehensive interventions targeted at DU-FSWs'
      injection drug using and high risk sexual behaviors are urgently needed to reduce
      the rapid spread of HIV epidemic.

PMID- 23555617
TI  - MLH1 promoter methylation frequency in colorectal cancer patients and related
      clinicopathological and molecular features.
AB  - PURPOSE: To describe the frequency of MLH1 promoter methylation in colorectal
      cancer (CRC); to explore the associations between MLH1 promoter methylation and
      clinicopathological and molecular factors using a systematic review and meta
      analysis. METHODS: A literature search of the PubMed and Embase databases was
      conducted to identify relevant articles published up to September 7, 2012 that
      described the frequency of MLH1 promoter methylation or its associations with
      clinicopathological and molecular factors in CRC. The pooled frequency, odds
      ratio (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: The
      pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95%
      CI: 16.8-24.1%). They were 18.7% (95% CI: 14.7-23.6%) and 16.4% (95% CI: 11.9
      22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant
      associations were observed between MLH1 promoter methylation and gender (pooled
      OR = 1.641, 95% CI: 1.215-2.215; P = 0.001), tumor location (pooled OR = 3.804,
      95% CI: 2.715-5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI:
      1.464-3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717-53.526; P<0.001).
      Significant associations were also observed between MLH1 promoter methylation and
      MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427-34.631;
      P<0.001) and 9.419 (95% CI: 2.613-33.953; P = 0.001), respectively). CONCLUSION:
      The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were
      18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter
      methylation may be significantly associated with gender, tumor location, tumor
      differentiation, MSI, MLH1 protein expression, and BRAF mutation.

PMID- 23555618
TI  - Vaginal practices among women at high risk of HIV infection in Uganda and
      Tanzania: recorded behaviour from a daily pictorial diary.
AB  - BACKGROUND: Intravaginal practices (IVP) are highly prevalent in sub-Saharan
      African and have been implicated as risk factors for HIV acquisition. However,
      types of IVP vary between populations, and detailed information on IVP among
      women at risk for HIV in different populations is needed. We investigated IVP
      among women who practice transactional sex in two populations: semi-urban,
      facility workers in Tanzania who engage in opportunistic sex work; and urban,
      self-identified sex workers and bar workers in Uganda. The aim of the study was
      to describe and compare IVP using a daily pictorial diary. METHODOLOGY/PRINCIPAL
      FINDINGS: Two hundred women were recruited from a HIV prevention intervention
      feasibility study in Kampala, Uganda and in North-West Tanzania. Women were given
      diaries to record IVP daily for six weeks. Baseline data showed that Ugandan
      participants had more lifetime partners and transactional sex than Tanzanian
      participants. Results from the diary showed that 96% of Tanzanian participants
      and 100% of Ugandan participants reported intravaginal cleansing during the six
      week study period. The most common types of cleansing were with water only or
      water and soap. In both countries, intravaginal insertion (e.g. with herbs) was
      less common than cleansing, but insertion was practiced by more participants in
      Uganda (46%) than in Tanzania (10%). In Uganda, participants also reported more
      frequent sex, and more insertion related to sex. In both populations, cleansing
      was more often reported on days with reported sex and during menstruation, and in
      Uganda, when participants experienced vaginal discomfort. Participants were more
      likely to cleanse after sex if they reported no condom use. CONCLUSIONS: While
      intravaginal cleansing was commonly practiced in both cohorts, there was higher
      frequency of cleansing and insertion in Uganda. Differences in IVP were likely to
      reflect differences in sexual behaviour between populations, and may warrant
      different approaches to interventions targeting IVP. Vaginal practices among
      women at high risk in Uganda and Tanzania: recorded behaviour from a daily
      pictorial diary.

PMID- 23555619
TI  - Contribution of the ELFG test in algorithms of non-invasive markers towards the
      diagnosis of significant fibrosis in chronic hepatitis C.
AB  - BACKGROUND AND AIMS: We aimed to determine the best algorithms for the diagnosis
      of significant fibrosis in chronic hepatitis C (CHC) patients using all available
      parameters and tests. PATIENTS AND METHODS: We used the database from our study
      of 507 patients with histologically proven CHC in which fibrosis was evaluated by
      liver biopsy (Metavir) and tests: Fibrometer(r), Fibrotest(r), Hepascore(r),
      Apri, ELFG, MP3, Forn's, hyaluronic acid, tissue inhibitor of metalloproteinase-1
      (TIMP1), MMP1, collagen IV and when possible FibroscanTM. For the first test we
      used 90% negative predictive value to exclude patients with F<=1, next an
      induction algorithm was applied giving the best tests with at least 80% positive
      predictive value for the diagnosis of F>=2. The algorithms were computed using
      the R Software C4.5 program to select the best tests and cut-offs. The algorithm
      was automatically induced without premises on the part of the investigators. We
      also examined the inter-observer variations after independent review of liver
      biopsies by two pathologists. A medico-economic analysis compared the screening
      strategies with liver biopsy. RESULTS: In "intention to diagnose" the best
      algorithms for F>=2 were Fibrometer (r), Fibrotest(r), or Hepascore(r) in first
      intention with the ELFG score in second intention for indeterminate cases. The
      percentage of avoided biopsies varied between 50% (Fibrotest(r) or
      Fibrometer(r)+ELFG) and 51% (Hepascore(r)+ELFG). In "per-analysis"
      FibroscanTM+ELFG avoided liver biopsy in 55% of cases. The diagnostic performance
      of these screening strategies was statistically superior to the usual
      combinations (Fibrometer(r) or Fibrotest(r)+FibroscanTM) and was cost effective.
      We note that the consensual review of liver biopsies between the two pathologists
      was mainly in favor of F1 (64-69%). CONCLUSION: The ELFG test could replace
      Fibroscan in most currently used algorithms for the diagnosis of significant
      fibrosis including for those patients for whom FibroscanTM is unusable.

PMID- 23555620
TI  - Effects of reduced weight maintenance and leptin repletion on functional
      connectivity of the hypothalamus in obese humans.
AB  - Treating obesity has proven to be an intractable challenge, in part, due to the
      difficulty of maintaining reduced weight. In our previous studies of in-patient
      obese subjects, we have shown that leptin repletion following a 10% or greater
      weight loss reduces many of the metabolic (decreased energy expenditure,
      sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral
      (delayed satiation) changes that favor regain of lost weight. FMRI studies of
      these same subjects have shown leptin-sensitive increases in activation of the
      right hypothalamus and reduced activation of the cingulate, medial frontal and
      parahippocampal gryi, following weight loss, in response to food stimuli. In the
      present study, we expanded our cohort of in-patient subjects and employed
      psychophysiological interaction (PPI) analysis to examine changes in the
      functional connectivity of the right hypothalamus. During reduced-weight
      maintenance with placebo injections, the functional connectivity of the
      hypothalamus increased with visual areas and the dorsal anterior cingulate
      (dorsal ACC) in response to food cues, consistent with higher sensitivity to
      food. During reduced-weight maintenance with leptin injections, however, the
      functional connectivity of the right hypothalamus increased with the mid-insula
      and the central and parietal operculae, suggesting increased coupling with the
      interoceptive system, and decreased with the orbital frontal cortex, frontal pole
      and the dorsal ACC, suggesting a down-regulated sensitivity to food. These
      findings reveal neural mechanisms that may underlie observed changes in
      sensitivity to food cues in the obese population during reduced-weight
      maintenance and leptin repletion.

PMID- 23555622
TI  - Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to
      protect against Mycobacterium tuberculosis infections in animal models.
AB  - Tuberculosis is an ongoing threat to global health, especially with the emergence
      of multi drug-resistant (MDR) and extremely drug-resistant strains that are
      motivating the search for new treatment strategies. One potential strategy is
      immunotherapy using Innate Defence Regulator (IDR) peptides that selectively
      modulate innate immunity, enhancing chemokine induction and cell recruitment
      while suppressing potentially harmful inflammatory responses. IDR peptides
      possess only modest antimicrobial activity but have profound immunomodulatory
      functions that appear to be influential in resolving animal model infections. The
      IDR peptides HH2, 1018 and 1002 were tested for their activity against two M.
      tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and
      in vivo models. All peptides showed no cytotoxic activity and only modest direct
      antimicrobial activity versus M. tuberculosis (MIC of 15-30 ug/ml). Nevertheless
      peptides HH2 and 1018 reduced bacillary loads in animal models with both the
      virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018
      led to a considerable reduction in lung inflammation as revealed by decreased
      pneumonia. These results indicate that IDR peptides have potential as a novel
      immunotherapy against TB.

PMID- 23555621
TI  - Diversity of natural self-derived ligands presented by different HLA class I
      molecules in transporter antigen processing-deficient cells.
AB  - The transporter associated with antigen processing (TAP) translocates the cytosol
      derived proteolytic peptides to the endoplasmic reticulum lumen where they
      complex with nascent human leukocyte antigen (HLA) class I molecules. Non
      functional TAP complexes and viral or tumoral blocking of these transporters
      leads to reduced HLA class I surface expression and a drastic change in the
      available peptide repertoire. Using mass spectrometry to analyze complex human
      leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP
      deficient cells, we identified 334 TAP-independent ligands naturally presented by
      four different HLA-A, -B, and -C class I molecules with very different TAP
      dependency from the same cell line. The repertoire of TAP-independent peptides
      examined favored increased peptide lengths and a lack of strict binding motifs
      for all four HLA class I molecules studied. The TAP-independent peptidome arose
      from 182 parental proteins, the majority of which yielded one HLA ligand. In
      contrast, TAP-independent antigen processing of very few cellular proteins
      generated multiple HLA ligands. Comparison between TAP-independent peptidome and
      proteome of several subcellular locations suggests that the secretory vesicle
      like organelles could be a relevant source of parental proteins for TAP
      independent HLA ligands. Finally, a predominant endoproteolytic peptidase
      specificity for Arg/Lys or Leu/Phe residues in the P(1) position of the scissile
      bond was found for the TAP-independent ligands. These data draw a new and
      intricate picture of TAP-independent pathways.

PMID- 23555623
TI  - Frequent engagement of RelB activation is critical for cell survival in multiple
      myeloma.
AB  - The NF-kappaB family of transcription factors has emerged as a key player in the
      pathogenesis of multiple myeloma (MM). NF-kappaB is activated by at least two
      major signaling pathways. The classical pathway results in the activation of
      mainly RelA containing dimers, whereas the alternative pathway leads to the
      activation of RelB/p52 and RelB/p50 heterodimers. Activating mutations in
      regulators of the alternative pathway have been identified in 17% of MM patients.
      However, the status of RelB activation per se and its role in the regulation of
      cell survival in MM has not been investigated. Here, we reveal that 40% of newly
      diagnosed MM patients have a constitutive RelB DNA-binding activity in CD138(+)
      tumor cells, and we show an association with increased expression of a subset of
      anti-apoptotic NF-kappaB target genes, such as cIAP2. Furthermore, we demonstrate
      that RelB exerts a crucial anti-apoptotic activity in MM cells. Our findings
      indicate that RelB activation is key for promoting MM cell survival through the
      upregulation of anti-apoptotic proteins. Altogether, our study provides the
      framework for the development of new molecules targeting RelB in the treatment of
      MM.

PMID- 23555624
TI  - Internet-delivered cognitive behavioural therapy for adults with mild to moderate
      depression and high cardiovascular disease risks: a randomised attention
      controlled trial.
AB  - BACKGROUND AND AIM: Mild to moderate depression is common in those with
      cardiovascular disease and undertreated. We aimed to evaluate the effectiveness
      of internet-delivered Cognitive Behaviour Therapy (iCBT) on depressive symptom
      severity and adherence to medical advice and lifestyle interventions in adults
      with mild to moderate depression and high cardiovascular disease (CVD) risks.
      METHODS: Randomised double-blind, 12 week attention-controlled trial comparing an
      iCBT programme (E-couch) with an internet-delivered attention control health
      information package (HealthWatch, n = 282). The primary outcome was depression
      symptom level on the nine-item Patient Health Questionnaire (PHQ-9) (trial
      registration: ACTRN12610000085077). RESULTS: 487/562 (88%) participants completed
      the endpoint assessment. 383/562 (70%) were currently treated for cardiovascular
      disease and 314/562 (56%) had at least one other comorbid condition. In ITT
      analysis of 562 participants iCBT produced a greater decline in the mean PHQ-9
      score compared to the attention control of 1.06 (95% CI: 0.23-1.89) points, with
      differences between the two arms increasing over the intervention period (time by
      treatment effect interaction p = .012). There were also larger improvements in
      adherence (2.16 points; 95% CI: 0.33-3.99), reductions in anxiety (0.96 points;
      95% CI: 0.19-1.73), and a greater proportion engaging in beneficial physical
      activity (Odds Ratio 1.91, 95%CI: 1.01-3.61) in the iCBT participants but no
      effect upon disability, or walking time/day. There were no withdrawals due to
      study related adverse events. CONCLUSIONS: In people with mild to moderate
      depression and high levels of CVD risk factors, a freely accessible iCBT
      programme (http://www.ecouch.anu.edu.au) produced a small, but robust,
      improvement in depressive symptoms, adherence and some health behaviours. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12610000085077.

PMID- 23555625
TI  - Antibacterial and cytotoxic efficacy of extracellular silver nanoparticles
      biofabricated from chromium reducing novel OS4 strain of Stenotrophomonas
      maltophilia.
AB  - Biofabricated metal nanoparticles are generally biocompatible, inexpensive, and
      ecofriendly, therefore, are used preferably in industries, medical and material
      science research. Considering the importance of biofabricated materials, we
      isolated, characterized and identified a novel bacterial strain OS4 of
      Stenotrophomonas maltophilia (GenBank: JN247637.1). At neutral pH, this Gram
      negative bacterial strain significantly reduced hexavalent chromium, an important
      heavy metal contaminant found in the tannery effluents and minings. Subsequently,
      even at room temperature the supernatant of log phase grown culture of strain OS4
      also reduced silver nitrate (AgNO3) to generate nanoparticles (AgNPs). These
      AgNPs were further characterized by UV-visible, Nanophox particle size analyzer,
      XRD, SEM and FTIR. As evident from the FTIR data, plausibly the protein
      components of supernatant caused the reduction of AgNO3. The cuboid and
      homogenous AgNPs showed a characteristic UV-visible peak at 428 nm with average
      size of ~93 nm. The XRD spectra exhibited the characteristic Bragg peaks of 111,
      200, 220 and 311 facets of the face centred cubic symmetry of nanoparticles
      suggesting that these nanoparticles were crystalline in nature. From the
      nanoparticle release kinetics data, the rapid release of AgNPs was correlated
      with the particle size and increasing surface area of the nanoparticles. A highly
      significant antimicrobial activity against medically important bacteria by the
      biofabricated AgNPs was also revealed as decline in growth of Staphylococcus
      aureus (91%), Escherichia coli (69%) and Serratia marcescens (66%) substantially.
      Additionally, different cytotoxic assays showed no toxicity of AgNPs to liver
      function, RBCs, splenocytes and HeLa cells, hence these particles were safe to
      use. Therefore, this novel bacterial strain OS4 is likely to provide broad
      spectrum benefits for curing chromium polluted sites, for biofabrication of AgNPs
      and ultimately in the nanoparticle based drug formulation for the treatment of
      infectious diseases.

PMID- 23555626
TI  - Health system barriers to access and use of magnesium sulfate for women with
      severe pre-eclampsia and eclampsia in Pakistan: evidence for policy and practice.
AB  - Severe pre-eclampsia and eclampsia are rare but serious complications of
      pregnancy that threaten the lives of mothers during childbirth. Evidence supports
      the use of magnesium sulfate (MgSO4) as the first line treatment option for
      severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of
      maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries
      (LMIC), it is suspected that MgSO4 is critically under-utilized in the country.
      There is however a lack of information on context-specific health system barriers
      that prevent optimal use of this life-saving medicine in Pakistan. Combining
      quantitative and qualitative methods, namely policy document review, key
      informant interviews, focus group discussions and direct observation at health
      facility, we explored context-specific health system barriers and enablers that
      affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in
      Pakistan. Our study finds that while international recommendations on MgSO4 have
      been adequately translated in national policies in Pakistan, the gap remains in
      implementation of national policies into practice. Barriers to access to and
      effective use of MgSO4 occur at health facility level where the medicine was not
      available and health staff was reluctant to use it. Low price of the medicine and
      the small market related to its narrow indications acted as disincentives for
      effective marketing. Results of our survey were further discussed in a multi
      stakeholder round-table meeting and an action plan for increasing access to this
      life-saving medicine was identified.

PMID- 23555627
TI  - Improvement of mercuric chloride-induced testis injuries and sperm quality
      deteriorations by Spirulina platensis in rats.
AB  - The present study was undertaken to investigate the protective effect of the
      filamentous cyanobacterium Spirulina platensis (S. platensis) on mercury (II)
      chloride (HgCl(2))-induced oxidative damages and histopathological alterations in
      the testis of Wistar albino rats. The animals were divided into four equal
      groups, i) control, ii) HgCl(2), iii) S. platensis and iv) combination of
      HgCl(2)+S. platensis. Oxidative stress, induced by a single dose of HgCl(2) (5
      mg/kg, bw; subcutaneously, s.c.), substantially decreased (P<0.01) the activity
      level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase,
      SOD; catalase, CAT and glutathione peroxidase, GPx), oxidative stress makers
      (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde,
      MDA), and testicular mercury levels. Moreover, HgCl(2) administration resulted in
      a significant (P<0.01) increase in the number of sperms with abnormal morphology
      and decrease in epididymal sperm count, motility, plasma testosterone level and
      testicular cholesterol. Furthermore, HgCl(2) exposure induced histopathological
      changes to the testis including morphological alterations of the seminiferous
      tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral
      pretreatment of animals with Spirulina (300 mg/kg, bw) lowered the extent of the
      observed HgCl(2)-mediated toxicity, whereby significantly reducing the resulting
      lipid peroxidation products, mercury accumulation in the testis,
      histopathological changes of the testes and spermatozoal abnormalities. In
      parallel, the pretreatment with Spirulina also completely reverted the observed
      Hg-Cl(2)-induced inhibition in enzymatic activities of antioxidant biomarkers
      (SOD, CAT and GPx) back to control levels. The pretreatment of rats with S.
      platensis significantly recovered the observed HgCl(2)-mediated decrease in the
      weight of accessory sex organs. Taken together, our findings clearly highlight
      the role of S. platensis as a protective modulator of HgCl(2)-induced testicular
      injuries and suggest some therapeutic potential in mammals. Further investigation
      of therapeutic strategies employing Spirulina against heavy metals toxicity in
      humans is therefore warranted.

PMID- 23555628
TI  - Optogenetic probing and manipulation of the calyx-type presynaptic terminal in
      the embryonic chick ciliary ganglion.
AB  - The calyx-type synapse of chick ciliary ganglion (CG) has been intensively
      studied for decades as a model system for the synaptic development, morphology
      and physiology. Despite recent advances in optogenetics probing and/or
      manipulation of the elementary steps of the transmitter release such as membrane
      depolarization and Ca(2+) elevation, the current gene-manipulating methods are
      not suitable for targeting specifically the calyx-type presynaptic terminals.
      Here, we evaluated a method for manipulating the molecular and functional
      organization of the presynaptic terminals of this model synapse. We transfected
      progenitors of the Edinger-Westphal (EW) nucleus neurons with an EGFP expression
      vector by in ovo electroporation at embryonic day 2 (E2) and examined the CG at
      E8-14. We found that dozens of the calyx-type presynaptic terminals and axons
      were selectively labeled with EGFP fluorescence. When a Brainbow construct
      containing the membrane-tethered fluorescent proteins m-CFP, m-YFP and m-RFP, was
      introduced together with a Cre expression construct, the color coding of each
      presynaptic axon facilitated discrimination among inter-tangled projections,
      particularly during the developmental re-organization period of synaptic
      connections. With the simultaneous expression of one of the chimeric variants of
      channelrhodopsins, channelrhodopsin-fast receiver (ChRFR), and R-GECO1, a red
      shifted fluorescent Ca(2+)-sensor, the Ca(2+) elevation was optically measured
      under direct photostimulation of the presynaptic terminal. Although this
      optically evoked Ca(2+) elevation was mostly dependent on the action potential, a
      significant component remained even in the absence of extracellular Ca(2+). It is
      suggested that the photo-activation of ChRFR facilitated the release of Ca(2+)
      from intracellular Ca(2+) stores directly or indirectly. The above system, by
      facilitating the molecular study of the calyx-type presynaptic terminal, would
      provide an experimental platform for unveiling the molecular mechanisms
      underlying the morphology, physiology and development of synapses.

PMID- 23555629
TI  - Genetic diversity and lack of artemisinin selection signature on the Plasmodium
      falciparum ATP6 in the Greater Mekong Subregion.
AB  - The recent detection of clinical Artemisinin (ART) resistance manifested as
      delayed parasite clearance in the Cambodia-Thailand border area raises a serious
      concern. The mechanism of ART resistance is not clear; but the P. falciparum
      sarco/endoplasmic reticulum Ca(2+)-ATPase (PfSERCA or PfATP6) has been speculated
      to be the target of ARTs and thus a potential marker for ART resistance. Here we
      amplified and sequenced pfatp6 gene (~3.6 Kb) in 213 samples collected after 2005
      from the Greater Mekong Subregion, where ART drugs have been used extensively in
      the past. A total of 24 single nucleotide polymorphisms (SNPs), including 8 newly
      found in this study and 13 nonsynonymous, were identified. However, these
      mutations were either uncommon or also present in other geographical regions with
      limited ART use. None of the mutations were suggestive of directional selection
      by ARTs. We further analyzed pfatp6 from a worldwide collection of 862 P.
      falciparum isolates in 19 populations from Asia, Africa, South America and
      Oceania, which include samples from regions prior to and after deployments ART
      drugs. A total of 71 SNPs were identified, resulting in 106 nucleotide
      haplotypes. Similarly, many of the mutations were continent-specific and present
      at frequencies below 5%. The most predominant and perhaps the ancestral haplotype
      occurred in 441 samples and was present in 16 populations from Asia, Africa, and
      Oceania. The 3D7 haplotype found in 54 samples was the second most common
      haplotype and present in nine populations from all four continents. Assessment of
      the selection strength on pfatp6 in the 19 parasite populations found that pfatp6
      in most of these populations was under purifying selection with an average
      d(N)/d(S) ratio of 0.333. Molecular evolution analyses did not detect significant
      departures from neutrality in pfatp6 for most populations, challenging the
      suitability of this gene as a marker for monitoring ART resistance.

PMID- 23555630
TI  - Prenatal exposure to a polychlorinated biphenyl (PCB) congener influences
      fixation duration on biological motion at 4-months-old: a preliminary study.
AB  - Adverse effects of prenatal exposure to polychlorinated biphenyl (PCB) congeners
      on postnatal brain development have been reported in a number of previous
      studies. However, few studies have examined the effects of prenatal PCB exposure
      on early social development. The present study sought to increase understanding
      of the neurotoxicity of PCBs by examining the relationship between PCB congener
      concentrations in umbilical cord blood and fixation patterns when observing
      upright and inverted biological motion (BM) at four-months after birth. The
      development of the ability to recognize BM stimuli is considered a hallmark of
      socio-cognitive development. The results revealed a link between dioxin-like PCB
      #118 concentration and fixation pattern. Specifically, four-month-olds with a low
      level of prenatal exposure to PCB #118 exhibited a preference for the upright BM
      over inverted BM, whereas those with a relatively high-level of exposure did not.
      This finding supports the proposal that prenatal PCB exposure impairs the
      development of social functioning, and indicates the importance of congener
      specific analysis in the risk analysis of the adverse effects of PCB exposure on
      the brain development.

PMID- 23555631
TI  - Immunogenicity of live attenuated B. pertussis BPZE1 producing the universal
      influenza vaccine candidate M2e.
AB  - BACKGROUND: Intranasal delivery of vaccines directed against respiratory
      pathogens is an attractive alternative to parenteral administration. However,
      using this delivery route for inactivated vaccines usually requires the use of
      potent mucosal adjuvants, and no such adjuvant has yet been approved for human
      use. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a live attenuated
      Bordetella pertussis vaccine, called BPZE1, and show here that it can be used to
      present the universal influenza virus epitope M2e to the mouse respiratory tract
      to prime for protective immunity against viral challenge. Three copies of M2e
      were genetically fused to the N-terminal domain of filamentous hemagglutinin
      (FHA) and produced in recombinant BPZE1 derivatives in the presence or absence of
      endogenous full-length FHA. Only in the absence of FHA intranasal administration
      of the recombinant BPZE1 derivative induced antibody responses to M2e and
      effectively primed BALB/c mice for protection against influenza virus-induced
      mortality and reduced the viral load after challenge. Strong M2e-specific
      antibody responses and protection were observed after a single nasal
      administration with the recombinant BPZE1 derivative, followed by a single
      administration of M2e linked to a virus-like particle without adjuvant, whereas
      priming alone with the vaccine strain did not protect. CONCLUSIONS/SIGNIFICANCE:
      Using recombinant FHA-3M2e-producing BPZE1 derivatives for priming and the
      universal influenza M2e peptide linked to virus-like particles for boosting may
      constitute a promising approach for needle-free and adjuvant-free nasal
      vaccination against influenza.

PMID- 23555632
TI  - Evidence for the circulation and inter-hemispheric movement of the H14 subtype
      influenza A virus.
AB  - Three H14 influenza A virus (IAV) isolates recovered in 2010 during routine virus
      surveillance along the Mississippi Migratory Bird Flyway in Wisconsin, U.S.A.
      raised questions about the natural history of these rare viruses. These were the
      first H14 IAV isolates recovered in the Western Hemisphere and the only H14 IAV
      isolates recovered since the original four isolates in 1982 in Asia. Full length
      genomic sequencing of the 2010 H14 isolates demonstrated the hemagglutinin (HA)
      gene from the 1982 and 2010 H14 isolates showed 89.6% nucleotide and 95.6% amino
      acid similarity and phylogenetic analysis of these viruses placed them with
      strong support within the H14 subtype lineage. The level of genomic divergence
      observed between the 1982 and 2010 viruses provides evidence that the H14 HA
      segment was circulating undetected in hosts and was not maintained in
      environmental stasis. Further, the evolutionary relationship observed between
      1982 H14 and the closely related H4 subtype HA segments were similar to
      contemporary comparisons suggesting limited adaptive divergence between these
      sister subtypes. The nonstructural (NS) segment of one 2010 isolate was placed in
      a NS clade isolated infrequently over the last several decades that includes the
      NS segment from a previously reported 1982 H14 isolate indicating the existence
      of an unidentified pool of genomic diversity. An additional neuraminidase
      reassortment event indicated a recent inter-hemispheric gene flow from Asia into
      the center of North America. These results demonstrate temporal and spatial gaps
      in the understanding of IAV natural history. Additionally, the reassortment
      history of these viruses raises concern for the inter-continental spread of IAVs
      and the efficacy of current IAV surveillance efforts in detecting genomic
      diversity of viruses circulating in wild birds.

PMID- 23555633
TI  - Automated universal BRAF state detection within the activation segment in skin
      metastases by pyrosequencing-based assay U-BRAF(V600).
AB  - Malignant melanoma is a highly-aggressive type of malignancy with considerable
      metastatic potential and frequent resistance to cytotoxic agents. BRAF mutant
      protein was recently recognized as therapeutic target in metastatic melanoma. We
      present a newly-developed U-BRAF(V600) approach - a universal pyrosequencing
      based assay for mutation detection within activation segment in exon 15 of human
      braf. We identified 5 different BRAF mutations in a single assay analyzing 75
      different formalin-fixed paraffin-embedded (FFPE) samples of cutaneous melanoma
      metastases from 29 patients. We found BRAF mutations in 21 of 29 metastases. All
      mutant variants were quantitatively detectable by the newly-developed U
      BRAF(V600) assay. These results were confirmed by ultra-deep-sequencing
      validation ((~)60,000-fold coverage). In contrast to all other BRAF state
      detection methods, the U-BRAF(V600) assay is capable of automated quantitative
      identification of at least 36 previously-published BRAF mutations. Under the
      precaution of a minimum of 3% mutated cells in front of a background of wild type
      cells, U-BRAFV600 assay design completely excludes false wild-type results. The
      corresponding algorithm for classification of BRAF-mutated variants is provided.
      The single-reaction assay and data analysis automation makes our approach
      suitable for the assessment of large clinical sample sizes. Therefore, we suggest
      U-BRAF(V600) assay as a most powerful sequencing-based diagnostic tool to
      automatically identify BRAF state as a prerequisite to targeted therapy.

PMID- 23555634
TI  - Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein
      from human herpesvirus 6B.
AB  - Infection with human herpesvirus (HHV)-6B alters cell cycle progression and
      stabilizes tumor suppressor protein p53. In this study, we have analyzed the
      activity of p53 after stimulation with p53-dependent and -independent DNA
      damaging agents during HHV-6B infection. Microarray analysis, Western blotting
      and confocal microscopy demonstrated that HHV-6B-infected cells were resistant to
      p53-dependent arrest and cell death after gamma irradiation in both permissive
      and non-permissive cell lines. In contrast, HHV-6B-infected cells died normally
      through p53-independet DNA damage induced by UV radiation. Moreover, we
      identified a viral protein involved in inhibition of p53 during HHV-6B-infection.
      The protein product from the U19 ORF was able to inhibit p53-dependent signaling
      following gamma irradiation in a manner similar to that observed during
      infection. Similar to HHV-6B infection, overexpression of U19 failed to rescue
      the cells from p53-independent death induced by UV radiation. Hence, infection
      with HHV-6B specifically blocks DNA damage-induced cell death associated with p53
      without inhibiting the p53-independent cell death response. This block in p53
      function can in part be ascribed to the activities of the viral U19 protein.

PMID- 23555635
TI  - Cartilage-specific over-expression of CCN family member 2/connective tissue
      growth factor (CCN2/CTGF) stimulates insulin-like growth factor expression and
      bone growth.
AB  - Previously we showed that CCN family member 2/connective tissue growth factor
      (CCN2) promotes the proliferation, differentiation, and maturation of growth
      cartilage cells in vitro. To elucidate the specific role and molecular mechanism
      of CCN2 in cartilage development in vivo, in the present study we generated
      transgenic mice overexpressing CCN2 and analyzed them with respect to cartilage
      and bone development. Transgenic mice were generated expressing a ccn2/lacZ
      fusion gene in cartilage under the control of the 6 kb-Col2a1-enhancer/promoter.
      Changes in cartilage and bone development were analyzed histologically and
      immunohistologically and also by micro CT. Primary chondrocytes as well as limb
      bud mesenchymal cells were cultured and analyzed for changes in expression of
      cartilage-related genes, and non-transgenic chondrocytes were treated in culture
      with recombinant CCN2. Newborn transgenic mice showed extended length of their
      long bones, increased content of proteoglycans and collagen II accumulation.
      Micro-CT analysis of transgenic bones indicated increases in bone thickness and
      mineral density. Chondrocyte proliferation was enhanced in the transgenic
      cartilage. In in vitro short-term cultures of transgenic chondrocytes, the
      expression of col2a1, aggrecan and ccn2 genes was substantially enhanced; and in
      long-term cultures the expression levels of these genes were further enhanced.
      Also, in vitro chondrogenesis was strongly enhanced. IGF-I and IGF-II mRNA levels
      were elevated in transgenic chondrocytes, and treatment of non-transgenic
      chondrocytes with recombinant CCN2 stimulated the expression of these mRNA. The
      addition of CCN2 to non-transgenic chondrocytes induced the phosphorylation of
      IGFR, and ccn2-overexpressing chondrocytes showed enhanced phosphorylation of
      IGFR. Our data indicates that the observed effects of CCN2 may be mediated in
      part by CCN2-induced overexpression of IGF-I and IGF-II. These findings indicate
      that CCN2-overexpression in transgenic mice accelerated the endochondral
      ossification processes, resulting in increased length of their long bones. Our
      results also indicate the possible involvement of locally enhanced IGF-I or IGF
      II in this extended bone growth.

PMID- 23555636
TI  - Longer telomere length in peripheral white blood cells is associated with risk of
      lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort
      study among women in China.
AB  - A recent genome-wide association study of lung cancer among never-smoking females
      in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on
      chromosome 5p15.33 was strongly and significantly associated with risk of
      adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase
      that is critical for telomere replication and stabilization by controlling
      telomere length. We previously found that longer telomere length measured in
      peripheral white blood cell DNA was associated with increased risk of lung cancer
      in a prospective cohort study of smoking males in Finland. To follow up on this
      finding, we carried out a nested case-control study of 215 female lung cancer
      cases and 215 female controls, 94% of whom were never-smokers, in the prospective
      Shanghai Women's Health Study cohort. There was a dose-response relationship
      between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95%
      confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P
      trend = 0.003). Further, the association was unchanged by the length of time from
      blood collection to case diagnosis. In addition, the rs2736100 G allele, which we
      previously have shown to be associated with risk of lung cancer in this cohort,
      was significantly associated with longer telomere length in these same study
      subjects (P trend = 0.030). Our findings suggest that individuals with longer
      telomere length in peripheral white blood cells may have an increased risk of
      lung cancer, but require replication in additional prospective cohorts and
      populations.

PMID- 23555637
TI  - Inhibition of Rho and Rac geranylgeranylation by atorvastatin is critical for
      preservation of endothelial junction integrity.
AB  - BACKGROUND: Small GTPases (guanosine triphosphate, GTP) are involved in many
      critical cellular processes, including inflammation, proliferation, and
      migration. GTP loading and isoprenylation are two important post-translational
      modifications of small GTPases, and are critical for their normal function. In
      this study, we investigated the role of post-translational modifications of small
      GTPases in regulating endothelial cell inflammatory responses and junctional
      integrity. METHODS AND RESULTS: Confluent human umbilical vein endothelial cell
      (HUVECs ) treated with atorvastatin demonstrated significantly decreased
      lipopolysaccharide (LPS)-mediated IL-6 and IL-8 generation. The inhibitory effect
      of atorvastatin (Atorva) was attenuated by co-treatment with 100 uM mevalonate
      (MVA) or 10 uM geranylgeranyl pyrophosphate (GGPP), but not by 10 uM farnesyl
      pyrophosphate (FPP). Atorvastatin treatment of HUVECs produced a time-dependent
      increase in GTP loading of all Rho GTPases, and induced the translocation of
      small Rho GTPases from the cellular membrane to the cytosol, which was reversed
      by 100 uM MVA and 10 uM GGPP, but not by 10 uM FPP. Atorvastatin significantly
      attenuated thrombin-induced HUVECs permeability, increased VE-cadherin targeting
      to cell junctions, and preserved junction integrity. These effects were partially
      reversed by GGPP but not by FPP, indicating that geranylgeranylation of small
      GTPases plays a major role in regulating endothelial junction integrity.
      Silencing of small GTPases showed that Rho and Rac, but not Cdc42, play central
      role in HUVECs junction integrity. CONCLUSIONS: In conclusion, our studies show
      that post-translational modification of small GTPases plays a vital role in
      regulating endothelial inflammatory response and endothelial junction integrity.
      Atorvastatin increased GTP loading and inhibited isoprenylation of small GTPases,
      accompanied by reduced inflammatory response and preserved cellular junction
      integrity.

PMID- 23555638
TI  - Acute colitis induces neurokinin 1 receptor internalization in the rat
      lumbosacral spinal cord.
AB  - Substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), play
      important roles in transmitting and regulating somatosensory nociceptive
      information. However, their roles in visceral nociceptive transmission and
      regulation remain to be elucidated. In the previous study, moderate SP
      immunoreactive (SP-ir) terminals and NK1R-ir neurons were observed in the dorsal
      commissural nucleus (DCN) of the lumbosacral spinal cord. Thus we hypothesized
      that the SP-NK1R system is involved in visceral pain transmission and control
      within the DCN. The acute visceral pain behaviors, the colon histological changes
      and the temporal and spatial changes of NK1R-ir structures and Fos expression in
      the neurons of the DCN were observed in rats following lower colon instillation
      with 5% formalin. The formalin instillation induced significant acute colitis as
      revealed by the histological changes in the colon. NK1R internalization in the
      DCN was obvious at 8 min. It reached a peak (75.3%) at 30 min, began to decrease
      at 90 min (58.1%) and finally reached the minimum (19.7%) at 3 h after
      instillation. Meanwhile, formalin instillation induced a biphasic visceral pain
      response as well as a strong expression of Fos protein in the nuclei of neurons
      in the DCN. Finally, intrathecal treatment with the NK1R antagonist L732138
      attenuated the NK1R internalization, Fos expression and visceral nociceptive
      responses. The present results suggest that the visceral nociceptive information
      arising from inflamed pelvic organs, such as the lower colon, might be mediated
      by the NK1R-ir neurons in the DCN of the lumbosacral spinal cord.

PMID- 23555639
TI  - Processing of continuously provided punishment and reward in children with ADHD
      and the modulating effects of stimulant medication: an ERP study.
AB  - OBJECTIVES: Current models of ADHD suggest abnormal reward and punishment
      sensitivity, but the exact mechanisms are unclear. This study aims to investigate
      effects of continuous reward and punishment on the processing of performance
      feedback in children with ADHD and the modulating effects of stimulant
      medication. METHODS: 15 Methylphenidate (Mph)-treated and 15 Mph-free children of
      the ADHD-combined type and 17 control children performed a selective attention
      task with three feedback conditions: no-feedback, gain and loss. Event Related
      Potentials (ERPs) time-locked to feedback and errors were computed. RESULTS: All
      groups performed more accurately with gain and loss than without feedback.
      Feedback-related ERPs demonstrated no group differences in the feedback P2, but
      an enhanced late positive potential (LPP) to feedback stimuli (both gains and
      losses) for Mph-free children with ADHD compared to controls. Feedback-related
      ERPs in Mph-treated children with ADHD were similar to controls. Correlational
      analyses in the ADHD groups revealed that the severity of inattention problems
      correlated negatively with the feedback P2 amplitude and positively with the LPP
      to losses and omitted gains. CONCLUSIONS: The early selective attention for
      rewarding and punishing feedback was relatively intact in children with ADHD, but
      the late feedback processing was deviant (increased feedback LPP). This may
      explain the often observed positive effects of continuous reinforcement on
      performance and behaviour in children with ADHD. However, these group findings
      cannot be generalised to all individuals with the ADHD, because the feedback
      related ERPs were associated with the severity of the inattention problems.
      Children with ADHD-combined type with more inattention problems showed both
      deviant early attentional selection of feedback stimuli, and deviant late
      processing of non-reward and punishment.

PMID- 23555640
TI  - TGF-beta superfamily gene expression and induction of the Runx1 transcription
      factor in adult neurogenic regions after brain injury.
AB  - Traumatic brain injury (TBI) increases neurogenesis in the forebrain
      subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). Transforming
      growth factor-beta (TGF-beta) superfamily cytokines are important regulators of
      adult neurogenesis, but their involvement in the regulation of this process after
      brain injury is unclear. We subjected adult mice to controlled cortical impact
      (CCI) injury, and isolated RNA from the SVZ and DG at different post-injury time
      points. qPCR array analysis showed that cortical injury caused significant
      alterations in the mRNA expression of components and targets of the TGF-beta,
      BMP, and activin signaling pathways in the SVZ and DG after injury, suggesting
      that these pathways could regulate post-injury neurogenesis. In both neurogenic
      regions, the injury also induced expression of Runt-related transcription factor
      1 (Runx1), which can interact with intracellular TGF-beta Smad signaling
      pathways. CCI injury strongly induced Runx1 expression in activated and
      proliferating microglial cells throughout the neurogenic regions. Runx1 protein
      was also expressed in a subset of Nestin- and GFAP-expressing putative neural
      stem or progenitor cells in the DG and SVZ after injury. In the DG only, these
      Runx1+ progenitors proliferated. Our data suggest potential roles for Runx1 in
      the processes of microglial cell activation and proliferation and in neural stem
      cell proliferation after TBI.

PMID- 23555641
TI  - Association among polymorphisms in EGFR gene exons, lifestyle and risk of gastric
      cancer with gender differences in Chinese Han subjects.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) gene plays a key role in
      tumor survival, invasion, angiogenesis, and metastatic spread. Recent studies
      showed that gastric cancer (GC) was associated with polymorphisms of the EGFR
      gene and environmental influences, such as lifestyle factors. In this study,
      seven known SNPs in EGFR exons were investigated in a high-risk Chinese
      population in Jiangsu province to test whether genetic variants of EGFR exons and
      lifestyle are associated with an increased risk of GC. METHODOLOGY/PRINCIPAL
      FINDINGS: A hospital-based case-control study was performed in Jiangsu province.
      The results showed that smoking, drinking and preference for salty food were
      significantly associated with the risk of GC. The differences of lifestyle
      between males and females might be as the reason of higher incidence rates in
      males than those in females. Seven exon SNPs were genotyped
      rs2227983,rs2072454,rs17337023,rs1050171,rs1140475, rs2293347, and rs28384375. It
      was noted that the variant rs2072454 T allele and TT genotype were significantly
      associated with an increased risk of GC. Interestingly, our result suggested the
      ACAGCA haplotype might be associated with decreased risk of GC. However, no
      significant association was examined between the other six SNPs and the risk of
      GC both in the total population and the age-matching population even with gender
      differences. CONCLUSIONS: Smoking, drinking and preference for salty food were
      significantly associated with the risk of GC in Jiangsu province with gender
      differences. Although only one SNP (rs2072454) was significantly associated with
      an increased risk of GC, combined the six EGFR exon SNPs together may be useful
      for predicting the risk of GC.

PMID- 23555642
TI  - Immunoregulatory effect of bifidobacteria strains in porcine intestinal
      epithelial cells through modulation of ubiquitin-editing enzyme A20 expression.
AB  - BACKGROUND: We previously showed that evaluation of anti-inflammatory activities
      of lactic acid bacteria in porcine intestinal epithelial (PIE) cells is useful
      for selecting potentially immunobiotic strains. OBJECTIVE: The aims of the
      present study were: i) to select potentially immunomodulatory bifidobacteria that
      beneficially modulate the Toll-like receptor (TLR)-4-triggered inflammatory
      response in PIE cells and; ii) to gain insight into the molecular mechanisms
      involved in the anti-inflammatory effect of immunobiotics by evaluating the role
      of TLR2 and TLR negative regulators in the modulation of proinflammatory cytokine
      production and activation of mitogen-activated protein kinase (MAPK) and nuclear
      factor-kappaB (NF-kappaB) pathways in PIE cells. RESULTS: Bifidobacteria longum
      BB536 and B. breve M-16V strains significantly downregulated levels of
      interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and IL-6 in PIE cells
      challenged with heat-killed enterotoxigenic Escherichia coli. Moreover, BB536 and
      M-16V strains attenuated the proinflammatory response by modulating the NF-kappaB
      and MAPK pathways. In addition, our findings provide evidence for a key role for
      the ubiquitin-editing enzyme A20 in the anti-inflammatory effect of immunobiotic
      bifidobacteria in PIE cells. CONCLUSIONS: We show new data regarding the
      mechanism involved in the anti-inflammatory effect of immunobiotics. Several
      strains with immunoregulatory capabilities used a common mechanism to induce
      tolerance in PIE cells. Immunoregulatory strains interacted with TLR2,
      upregulated the expression of A20 in PIE cells, and beneficially modulated the
      subsequent TLR4 activation by reducing the activation of MAPK and NF-kappaB
      pathways and the production of proinflammatory cytokines. We also show that the
      combination of TLR2 activation and A20 induction can be used as biomarkers to
      screen and select potential immunoregulatory bifidobacteria strains.

PMID- 23555643
TI  - Detection of mouse cough based on sound monitoring and respiratory airflow
      waveforms.
AB  - Detection for cough in mice has never yielded clearly audible sounds, so there is
      still a great deal of debates as to whether mice can cough in response to tussive
      stimuli. Here we introduce an approach for detection of mouse cough based on
      sound monitoring and airflow signals. 40 Female BALB/c mice were pretreated with
      normal saline, codeine, capasazepine or desensitized with capsaicin. Single mouse
      was put in a plethysmograph, exposed to aerosolized 100 umol/L capsaicin for 3
      min, followed by continuous observation for 3 min. Airflow signals of total 6 min
      were recorded and analyzed to detect coughs. Simultaneously, mouse cough sounds
      were sensed by a mini-microphone, monitored manually by an operator. When manual
      and automatic detection coincided, the cough was positively identified. Sound and
      sound waveforms were also recorded and filtered for further analysis. Body
      movements were observed by operator. Manual versus automated counts were
      compared. Seven types of airflow signals were identified by integrating manual
      and automated monitoring. Observation of mouse movements and analysis of sound
      waveforms alone did not produce meaningful data. Mouse cough numbers decreased
      significantly after all above drugs treatment. The Bland-Altman and consistency
      analysis between automatic and manual counts was 0.968 and 0.956. The study
      suggests that the mouse is able to present with cough, which could be detected by
      sound monitoring and respiratory airflow waveform changes.

PMID- 23555644
TI  - The Jarisch-Herxheimer reaction in leptospirosis: a systematic review.
AB  - BACKGROUND: Leptospirosis is an endemo-epidemic zoonotic disease associated with
      potentially fatal renal, cardiovascular or pulmonary failure. Recommended
      treatment includes antibiotics, which may induce a Jarisch-Herxheimer reaction
      (JHR). Since little information on the importance of this adverse event is
      available, we performed this review to quantify frequency and impact of JHR in
      leptospirosis management. METHODOLOGY/PRINCIPAL FINDINGS: This review
      systematically summarizes the literature on the JHR in leptospirosis. To approach
      the broader aspects of the subject, articles considering the treatment of
      leptospirosis, national leptospirosis guidelines and textbook and technical
      reports of the World Health Organisation were reviewed. Publications describing
      JHR in leptospirosis are very limited and consist mainly of single case reports
      and small case series. A single randomized control trial specifically assessed
      the JHR occurrence, but it has never been systematically investigated in large
      trials. Not all guidelines and not all literature on leptospirosis mention this
      reaction which can be fatal. CONCLUSIONS/SIGNIFICANCE: Although generally assumed
      to be a rare event, the true prevalence of JHR in leptospirosis is unknown and
      the awareness of this event is insufficient. All leptospirosis guidelines and
      local leptospirosis protocols should stress on systematic monitoring for clinical
      status early after antibiotic administration. Large well designed studies are
      required to precise the incidence and the impact of JHR as well as the severity
      and rates between various antibiotics.

PMID- 23555645
TI  - Intratumour diversity of chromosome copy numbers in neuroblastoma mediated by on
      going chromosome loss from a polyploid state.
AB  - Neuroblastomas (NBs) are tumours of the sympathetic nervous system accounting for
      8-10% of paediatric cancers. NBs exhibit extensive intertumour genetic
      heterogeneity, but their extent of intratumour genetic diversity has remained
      unexplored. We aimed to assess intratumour genetic variation in NBs with a focus
      on whole chromosome changes and their underlying mechanism. Allelic ratios
      obtained by SNP-array data from 30 aneuploid primary NBs and NB cell lines were
      used to quantify the size of clones harbouring specific genomic imbalances. In 13
      cases, this was supplemented by fluorescence in situ hybridisation to assess copy
      number diversity in detail. Computer simulations of different mitotic segregation
      errors, single cell cloning, analysis of mitotic figures, and time lapse imaging
      of dividing NB cells were used to infer the most likely mechanism behind
      intratumour variation in chromosome number. Combined SNP array and FISH analyses
      showed that all cases exhibited higher inter-cellular copy number variation than
      non-neoplastic control tissue, with up to 75% of tumour cells showing non-modal
      chromosome copy numbers. Comparisons of copy number profiles, resulting from
      simulations of different segregation errors to genomic profiles of 120 NBs
      indicated that loss of chromosomes from a tetraploid state was more likely than
      other mechanisms to explain numerical aberrations in NB. This was supported by a
      high frequency of lagging chromosomes at anaphase and polyploidisation events in
      growing NB cells. The dynamic nature of numerical aberrations was corroborated
      further by detecting substantial copy number diversity in cell populations grown
      from single NB cells. We conclude that aneuploid NBs typically show extensive
      intratumour chromosome copy number diversity, and that this phenomenon is most
      likely explained by continuous loss of chromosomes from a polyploid state.

PMID- 23555647
TI  - Association of over-the-counter pharmaceutical sales with influenza-like
      illnesses to patient volume in an urgent care setting.
AB  - We studied the association between OTC pharmaceutical sales and volume of
      patients with influenza-like-illnesses (ILI) at an urgent care center over one
      year. OTC pharmaceutical sales explain 36% of the variance in the patient volume,
      and each standard deviation increase is associated with 4.7 more patient visits
      to the urgent care center (p<0.0001). Cross-correlation function analysis
      demonstrated that OTC pharmaceutical sales are significantly associated with
      patient volume during non-flu season (p<0.0001), but only the sales of cough and
      cold (p<0.0001) and thermometer (p<0.0001) categories were significant during flu
      season with a lag of two and one days, respectively. Our study is the first study
      to demonstrate and measure the relationship between OTC pharmaceutical sales and
      urgent care center patient volume, and presents strong evidence that OTC sales
      predict urgent care center patient volume year round.

PMID- 23555648
TI  - Atomic force microscopy analysis of progenitor corneal epithelial cells
      fractionated by a rapid centrifugation isolation technique.
AB  - PURPOSE: To investigate the use of atomic force microscopy (AFM) to image the
      three groups of corneal epithelial cells fractionated by a novel rapid
      centrifugation isolation technique. METHODS: Epithelial cells harvested from
      primary cultures of rabbit limbal rings were centrifuged onto uncoated dishes,
      first at 1400 rpm and then at 1800 rpm. The adherent cells after centrifugation
      at 1400 rpm (ATC1), the adherent cells at 1800 rpm (ATC2) and the non-adherent
      cells at 1800 rpm (NAC) were investigated for BrdU retention and were subjected
      to contact mode AFM and Transmission Electron Microscopy (TEM). RESULTS: Compared
      with unfractionated cells, the ATC1 group, accounting for about 10% of the whole
      population, was enriched in BrdU label-retaining cells. There were dramatic
      overall shape, surface membrane and intra-cellular ultrastructure differences
      noted among ATC1, ATC2 and NAC populations. The whole cell roughness measurements
      were 21.1+/-1.5 nm, 79.5+/-3.4 nm and 103+/-4.6 nm for the ATC1, ATC2 and NAC
      groups, respectively. The mero-nucleus roughness measurements were 34.2+/-1.7 nm,
      13.0+/-0.8 nm and 8.5+/-0.5 nm in the ATC1, ATC2 and NAC populations,
      respectively. CONCLUSIONS: AFM was found to be a good tool for distinguishing
      among the three groups of cells. BrdU label retention, the AFM parameters and TEM
      together suggest that the ATC1, ATC2 and NAC populations may be progenitor
      corneal epithelial cells, transit amplifying cells and terminal differentiation
      cells, respectively.

PMID- 23555646
TI  - Investigation of hydrogen sulfide gas as a treatment against P. falciparum,
      murine cerebral malaria, and the importance of thiolation state in the
      development of cerebral malaria.
AB  - INTRODUCTION: Cerebral malaria (CM) is a potentially fatal cerebrovascular
      disease of complex pathogenesis caused by Plasmodium falciparum. Hydrogen sulfide
      (HS) is a physiological gas, similar to nitric oxide and carbon monoxide,
      involved in cellular metabolism, vascular tension, inflammation, and cell death.
      HS treatment has shown promising results as a therapy for cardio- and neuro-
      pathology. This study investigates the effects of fast (NaHS) and slow (GYY4137)
      HS-releasing drugs on the growth and metabolism of P. falciparum and the
      development of P. berghei ANKA CM. Moreover, we investigate the role of free
      plasma thiols and cell surface thiols in the pathogenesis of CM. METHODS: P.
      falciparum was cultured in vitro with varying doses of HS releasing drugs
      compared with artesunate. Growth and metabolism were quantified. C57Bl/6 mice
      were infected with P. berghei ANKA and were treated with varying doses and
      regimes of HS-releasing drugs. Free plasma thiols and cell surface thiols were
      quantified in CM mice and age-matched healthy controls. RESULTS: HS-releasing
      drugs significantly and dose-dependently inhibited P. falciparum growth and
      metabolism. Treatment of CM did not affect P. berghei growth, or development of
      CM. Interestingly, CM was associated with lower free plasma thiols, reduced
      leukocyte+erythrocyte cell surface thiols (infection day 3), and markedly (5
      fold) increased platelet cell surface thiols (infection day 7). CONCLUSIONS: HS
      inhibits P. falciparum growth and metabolism in vitro. Reduction in free plasma
      thiols, cell surface thiols and a marked increase in platelet cell surface thiols
      are associated with development of CM. HS drugs were not effective in vivo
      against murine CM.

PMID- 23555649
TI  - Genetic characterization of natural variants of Vpu from HIV-1 infected
      individuals from Northern India and their impact on virus release and cell death.
AB  - BACKGROUND: Genetic studies reveal that vpu is one of the most variable regions
      in HIV-1 genome. Functional studies have been carried out mostly with Vpu derived
      from laboratory adapted subtype B pNL 4-3 virus. The rationale of this study was
      to characterize genetic variations that are present in the vpu gene from HIV-1
      infected individuals from North-India (Punjab/Haryana) and determine their
      functional relevance. METHODS: Functionally intact vpu gene variants were PCR
      amplified from genomic DNA of HIV-1 infected individuals. These variants were
      then subjected to genetic analysis and unique representative variants were cloned
      under CMV promoter containing expression vector as well as into pNL 4-3 HIV-1
      virus for intracellular expression studies. These variants were characterized
      with respect to their ability to promote virus release as well as cell death.
      RESULTS: Based on phylogenetic analysis and extensive polymorphisms with respect
      to consensus Vpu B and C, we were able to arbitrarily assign variants into two
      major groups (B and C). The group B variants always showed significantly higher
      virus release activity and exhibited moderate levels of cell death. On the other
      hand, group C variants displayed lower virus release activity but greater cell
      death potential. Interestingly, Vpu variants with a natural S61A mutation showed
      greater intracellular stability. These variants also exhibited significant
      reduction in their intracellular ubiquitination and caused greater virus release.
      Another group C variant that possessed a non-functional beta-TrcP binding motif
      due to two critical serine residues (S52 and S56) being substituted with
      isoleucine residues, showed reduced virus release activity but modest cytotoxic
      activity. CONCLUSIONS: The natural variations exhibited by our Vpu variants
      involve extensive polymorphism characterized by substitution and deletions that
      contribute toward positive selection. We identified two major groups and an
      extremely rare beta-TrcP binding motif mutant that show widely varying biological
      activities with potential implications for conferring subtype-specific
      pathogenesis.

PMID- 23555650
TI  - Diagnostic performance of a rapid magnetic resonance imaging method of measuring
      hepatic steatosis.
AB  - OBJECTIVES: Hepatic steatosis is associated with an increased risk of developing
      serious liver disease and other clinical sequelae of the metabolic syndrome.
      However, visual estimates of steatosis from histological sections of biopsy
      samples are subjective and reliant on an invasive procedure with associated
      risks. The aim of this study was to test the ability of a rapid, routinely
      available, magnetic resonance imaging (MRI) method to diagnose clinically
      relevant grades of hepatic steatosis in a cohort of patients with diverse liver
      diseases. MATERIALS AND METHODS: Fifty-nine patients with a range of liver
      diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly
      using an opposed-phase, in-phase gradient echo, single breath-hold MRI
      methodology and secondly, using liver biopsy with visual estimation by a
      histopathologist and by computer-assisted morphometric image analysis. The area
      under the receiver operating characteristic (ROC) curve was used to assess the
      diagnostic performance of the MRI method against the biopsy observations.
      RESULTS: The MRI approach had high sensitivity and specificity at all hepatic
      steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at
      thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were
      strongly associated with visual (r(2) = 0.83) and computer-assisted morphometric
      (r(2) = 0.84) estimates of hepatic steatosis from histological specimens.
      CONCLUSIONS: This MRI approach, using a conventional, rapid, gradient echo
      method, has high sensitivity and specificity for diagnosing liver fat at all
      grades of steatosis in a cohort with a range of liver diseases.

PMID- 23555651
TI  - A systematic in silico search for target similarity identifies several approved
      drugs with potential activity against the Plasmodium falciparum apicoplast.
AB  - Most of the drugs in use against Plasmodium falciparum share similar modes of
      action and, consequently, there is a need to identify alternative potential drug
      targets. Here, we focus on the apicoplast, a malarial plastid-like organelle of
      algal source which evolved through secondary endosymbiosis. We undertake a
      systematic in silico target-based identification approach for detecting drugs
      already approved for clinical use in humans that may be able to interfere with
      the P. falciparum apicoplast. The P. falciparum genome database GeneDB was used
      to compile a list of ~600 proteins containing apicoplast signal peptides. Each of
      these proteins was treated as a potential drug target and its predicted sequence
      was used to interrogate three different freely available databases (Therapeutic
      Target Database, DrugBank and STITCH3.1) that provide synoptic data on drugs and
      their primary or putative drug targets. We were able to identify several drugs
      that are expected to interact with forty-seven (47) peptides predicted to be
      involved in the biology of the P. falciparum apicoplast. Fifteen (15) of these
      putative targets are predicted to have affinity to drugs that are already
      approved for clinical use but have never been evaluated against malaria
      parasites. We suggest that some of these drugs should be experimentally tested
      and/or serve as leads for engineering new antimalarials.

PMID- 23555652
TI  - Meiofauna metabolism in suboxic sediments: currently overestimated.
AB  - Oxygen is recognized as a structuring factor of metazoan communities in marine
      sediments. The importance of oxygen as a controlling factor on meiofauna (32 um-1
      mm in size) respiration rates is however less clear. Typically, respiration rates
      are measured under oxic conditions, after which these rates are used in food web
      studies to quantify the role of meiofauna in sediment carbon turnover. Sediment
      oxygen concentration ([O(2)]) is generally far from saturated, implying that (1)
      current estimates of the role of meiofauna in carbon cycling may be biased and
      (2) meiofaunal organisms need strategies to survive in oxygen-stressed
      environments. Two main survival strategies are often hypothesized: 1) frequent
      migration to oxic layers and 2) morphological adaptation. To evaluate these
      hypotheses, we (1) used a model of oxygen turnover in the meiofauna body as a
      function of ambient [O(2)], and (2) performed respiration measurements at a range
      of [O(2)] conditions. The oxygen turnover model predicts a tight coupling between
      ambient [O(2)] and meiofauna body [O(2)] with oxygen within the body being
      consumed in seconds. This fast turnover favors long and slender organisms in
      sediments with low ambient [O(2)] but even then frequent migration between
      suboxic and oxic layers is for most organisms not a viable strategy to alleviate
      oxygen limitation. Respiration rates of all measured meiofauna organisms slowed
      down in response to decreasing ambient [O(2)], with Nematoda displaying the
      highest metabolic sensitivity for declining [O(2)] followed by Foraminifera and
      juvenile Gastropoda. Ostracoda showed a behavioral stress response when ambient
      [O(2)] reached a critical level. Reduced respiration at low ambient [O(2)]
      implies that meiofauna in natural, i.e. suboxic, sediments must have a lower
      metabolism than inferred from earlier respiration rates conducted under oxic
      conditions. The implications of these findings are discussed for the contribution
      of meiofauna to carbon cycling in marine sediments.

PMID- 23555653
TI  - Heavy ion radiation exposure triggered higher intestinal tumor frequency and
      greater beta-catenin activation than gamma radiation in APC(Min/+) mice.
AB  - Risk of colorectal cancer (CRC) after exposure to low linear energy transfer (low
      LET) radiation such as gamma-ray is highlighted by the studies in atom bomb
      survivors. On the contrary, CRC risk prediction after exposure to high-LET cosmic
      heavy ion radiation exposure is hindered due to scarcity of in vivo data.
      Therefore, intestinal tumor frequency, size, cluster, and grade were studied in
      APC(Min/+) mice (n = 20 per group; 6 to 8 wks old; female) 100 to 110 days after
      exposure to 1.6 or 4 Gy of heavy ion (56)Fe radiation (energy: 1000 MeV/nucleon)
      and results were compared to gamma radiation doses of 2 or 5 Gy, which are
      equitoxic to 1.6 and 4 Gy (56)Fe respectively. Due to relevance of lower doses to
      radiotherapy treatment fractions and space exploration, we followed 2 Gy gamma
      and equitoxic 1.6 Gy (56)Fe for comparative analysis of intestinal epithelial
      cell (IEC) proliferation, differentiation, and beta-catenin signaling pathway
      alterations between the two radiation types using immunoblot, and
      immunohistochemistry. Relative to controls and gamma-ray, intestinal tumor
      frequency and grade was significantly higher after (56)Fe radiation.
      Additionally, tumor incidence per unit of radiation (per cGy) was also higher
      after (56)Fe radiation relative to gamma radiation. Staining for phospho-histone
      H3, indicative of IEC proliferation, was more and alcian blue staining,
      indicative of IEC differentiation, was less in (56)Fe than gamma irradiated
      samples. Activation of beta-catenin was more in (56)Fe-irradiated tumor-free and
      tumor-bearing areas of the intestinal tissues. When considered along with higher
      levels of cyclin D1, we infer that relative to gamma radiation exposure to (56)Fe
      radiation induced markedly reduced differentiation, and increased proliferative
      index in IEC resulting in increased intestinal tumors of larger size and grade
      due to preferentially greater activation of beta-catenin and its downstream
      effectors.

PMID- 23555654
TI  - Gefitinib or erlotinib as maintenance therapy in patients with advanced stage non
      small cell lung cancer: a systematic review.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKI), gefitinib and erlotinib have been tested as maintenance therapy in
      patients with advanced non-small-cell lung cancer (NSCLC). The studies are quite
      heterogenous regarding study size and populations, and a synopsis of these data
      could give some more insight in the role of maintenance therapy with TKI.
      METHODS: In September 2012 we performed a search in the pubmed, EMBASE and
      Cochrane library databases for randomized phase III trials exploring the role of
      gefitinib or erlotinib in advanced non-small cell lung cancer. Through a rigorous
      selection process with specific criteria, five trials (n = 2436 patients) were
      included for analysis. Standard statistical methods for meta-analysis were
      applied. RESULTS: TKIs (gefitinib and erlotinib) significantly increased
      progression-free survival (PFS) [hazard ratio (HR) 0.63, 95% confidence interval
      (CI) 0.50-0.76, I(2) = 78.1%] and overall survival (HR 0.84, 95% CI 0.76-0.93,
      I(2) = 0.0%) compared with placebo or observation. The PFS benefit was consistent
      in all subgroups including stage, sex, ethnicity, performance status, smoking
      status, histology, EGFR mutation status, and previous response to chemotherapy.
      Patients with clinical features such as female, never smoker, adenocarcinoma,
      Asian ethnicity and EGFR mutation positive had more pronounced PFS benefit.
      Overall survival benefit was observed in patients with clinical features such as
      female, non-smoker, smoker, adenocarcinoma, and previous stable to induction
      chemotherapy. Severe adverse events were not frequent. Main limitations of this
      analysis are that it is not based on individual patient data, and not all studies
      provided detailed subgroups analysis. CONCLUSIONS: The results show that
      maintenance therapy with erlotinib or gefitinib produces a significant PFS and OS
      benefit for unselected patients with advanced NSCLC compared with placebo or
      observation. Given the less toxicity of TKIs than chemotherapy and simple oral
      administration, this treatment strategy seems to be of important clinical value.

PMID- 23555656
TI  - Niche segregation between wild and domestic herbivores in Chilean Patagonia.
AB  - Competition arises when two co-occuring species share a limiting resource.
      Potential for competition is higher when species have coexisted for a short time,
      as it is the case for herbivores and livestock introduced in natural systems.
      Sheep, introduced in the late 19(th) century in Patagonia, bear a great
      resemblance in size and diet to the guanaco, the main native herbivore in
      Patagonia. In such circumstances, it could be expected that the two species
      compete and one of them could be displaced. We investigated spatial overlap and
      habitat selection by coexisting sheep and guanaco in winter and in summer.
      Additionally, we studied habitat selection of the guanaco in a control situation
      free from sheep, both in summer and winter. We also determined overlap between
      species in areas with different intensity of use (named preferred and marginal
      areas) in order to further detect the potential level of competition in the case
      of overlapping. Guanaco and sheep showed significantly different habitat
      preferences through all seasons, in spite of their spatial overlap at landscape
      scale. Additionally, the habitat used by guanaco was similar regardless of the
      presence or absence of livestock, which further indicates that sheep is not
      displacing guanaco where they coexist. These results suggest that habitat
      segregation between guanaco and sheep is due to a differential habitat selection
      and not to a competitive displacement process. Therefore, the potential for
      competition is considered low, contrary to what has been previously observed,
      although this could be a density-dependent result.

PMID- 23555655
TI  - Molecular study of dietary heptadecane for the anti-inflammatory modulation of NF
      kB in the aged kidney.
AB  - Heptadecane is a volatile component of Spirulina platensis, and blocks the de
      novo synthesis of fatty acids and ameliorates several oxidative stress-related
      diseases. In a redox state disrupted by oxidative stress, pro-inflammatory genes
      are upregulated by the activation of NF-kB via diverse kinases. Thus, the search
      and characterization of new substances that modulate NF-kB are lively research
      topics. In the present study, heptadecane was examined in terms of its ability to
      suppress inflammatory NF-kB activation via redox-related NIK/IKK and MAPKs
      pathway in aged rats. In the first part of the study, Fischer 344 rats, aged 9
      and 20 months, were administered on average approximately 20 or 40 mg/Kg body
      weight over 10 days. The potency of heptadecane was investigated by examining its
      ability to suppress the gene expressions of COX-2 and iNOS (both NF-kappaB
      related genes) and reactive species (RS) production in aged kidney tissue. In the
      second part of the study, YPEN-1 cells (an endothelial cell line) were used to
      explore the molecular mechanism underlying the anti-inflammatory effect of
      heptadecane by examining its modulation of NF-kB and NF-kB signal pathway.
      Results showed that heptadecane exhibited a potent anti-oxidative effect by
      protecting YPEN-1 cells from tert-butylhydroperoxide induced oxidative stress.
      Further molecular investigations revealed that heptadecane attenuated RS-induced
      NF-kB via the NIK/IKK and MAPKs pathways in YPEN-1 cells and aged kidney tissues.
      Based on these results, we conclude that heptadecane suppresses age-related
      increases in pro-inflammatory gene expressions by reducing NF-kB activity by
      upregulating the NIK/IKK and MAPKs pathways induced by RS. These findings provide
      molecular insight of the mechanisms by which heptadecane exerts its
      antiinflammatory effect in aged kidney tissues. We conclude that heptadecane
      suppresses age-related increases in pro-inflammatory gene expressions then travel
      upstream set by step by reducing NF-kB activity by downregulating the NIK/IKK and
      MAPKs pathways induced by RS.

PMID- 23555657
TI  - Housing shortages in urban regions: aggressive interactions at tree hollows in
      forest remnants.
AB  - Urbanisation typically results in a reduction of hollow-bearing trees and an
      increase in the density of particularly species, potentially resulting in an
      increased level of competition as cavity-nesting species compete for a limited
      resource. To improve understanding of hollow usage between urban cavity-nesting
      species in Australia, particularly parrots, we investigated how the hollow-using
      assemblage, visitation rate, diversity and number of interactions varied between
      hollows within urban remnant forest and continuous forest. Motion-activated video
      cameras were installed, via roped access to the canopy, and hollow usage was
      monitored at 61 hollows over a two-year period. Tree hollows within urban
      remnants had a significantly different assemblage of visitors to those in
      continuous forest as well as a higher rate of visitation than hollows within
      continuous forest, with the rainbow lorikeet making significantly more
      visitations than any other taxa. Hollows within urban remnants were characterised
      by significantly higher usage rates and significantly more aggressive
      interactions than hollows within continuous forest, with parrots responsible for
      almost all interactions. Within urban remnants, high rates of hollow visitation
      and both interspecific and intraspecific interactions observed at tree hollows
      suggest the number of available optimal hollows may be limiting. Understanding
      the usage of urban remnant hollows by wildlife, as well as the role of parrots as
      a potential flagship for the conservation of tree-hollows, is vital to prevent a
      decrease in the diversity of urban fauna, particularly as other less competitive
      species risk being outcompeted by abundant native species.

PMID- 23555658
TI  - RNA interference of GADD153 protects photoreceptors from endoplasmic reticulum
      stress-mediated apoptosis after retinal detachment.
AB  - BACKGROUND: Apoptosis of photoreceptors plays a critical role in the vision loss
      caused by retinal detachment (RD). Pharmacologic inhibition of photoreceptor cell
      death may prevent RD. This study investigated the role of GADD153 that
      participates in endoplasmic reticulum (ER) stress-mediated apoptosis of
      photoreceptor cells after RD. METHODS: Retinal detachment was created in Wistar
      rats by subretinal injection of hyaluronic acid. The rats were then randomly
      divided into four groups: normal control group, RD group, GADD153 RNAi group and
      vehicle group. RNA interference of GADD153 was performed using short hairpin RNA
      (shRNA). Expressions of GADD153 mRNA and protein were examined by RT-PCR and
      Western blotting analysis, respectively. GADD153 protein distribution in the
      retinal cells was observed using immunofluorescence confocal laser scanning
      microscopy. Apoptosis of retinal cells was determined by TdT-mediated fluorescein
      16-dUTP nick-end labeling (TUNEL) assay. RESULTS: Lentivirus GADD153 shRNA with
      the most effective silencing effect was chosen for in vivo animal study and was
      successfully delivered into the retinal tissues. GADD153 mRNA and protein
      expressions in GADD153 RNAi group were significantly lower than those in the RD
      group. Silencing of GADD153 by RNAi protected photoreceptors from ER stress
      induced apoptosis. CONCLUSION: ER stress-mediated pathway is involved in
      photoreceptor cell apoptosis after RD. GADD153 is a key regulatory molecule
      regulating ER-stress pathways and plays a crucial role in the apoptosis of
      photoreceptor cells after RD.

PMID- 23555659
TI  - Multiple single-cell genomes provide insight into functions of uncultured
      Deltaproteobacteria in the human oral cavity.
AB  - Despite a long history of investigation, many bacteria associated with the human
      oral cavity have yet to be cultured. Studies that correlate the presence or
      abundance of uncultured species with oral health or disease highlight the
      importance of these community members. Thus, we sequenced several single-cell
      genomic amplicons from Desulfobulbus and Desulfovibrio (class
      Deltaproteobacteria) to better understand their function within the human oral
      community and their association with periodontitis, as well as other systemic
      diseases. Genomic data from oral Desulfobulbus and Desulfovibrio species were
      compared to other available deltaproteobacterial genomes, including from a subset
      of host-associated species. While both groups share a large number of genes with
      other environmental Deltaproteobacteria genomes, they encode a wide array of
      unique genes that appear to function in survival in a host environment. Many of
      these genes are similar to virulence and host adaptation factors of known human
      pathogens, suggesting that the oral Deltaproteobacteria have the potential to
      play a role in the etiology of periodontal disease.

PMID- 23555660
TI  - Genomic evaluation of Thermoanaerobacter spp. for the construction of designer co
      cultures to improve lignocellulosic biofuel production.
AB  - The microbial production of ethanol from lignocellulosic biomass is a multi
      component process that involves biomass hydrolysis, carbohydrate transport and
      utilization, and finally, the production of ethanol. Strains of the genus
      Thermoanaerobacter have been studied for decades due to their innate abilities to
      produce comparatively high ethanol yields from hemicellulose constituent sugars.
      However, their inability to hydrolyze cellulose, limits their usefulness in
      lignocellulosic biofuel production. As such, co-culturing Thermoanaerobacter spp.
      with cellulolytic organisms is a plausible approach to improving lignocellulose
      conversion efficiencies and yields of biofuels. To evaluate native
      lignocellulosic ethanol production capacities relative to competing fermentative
      end-products, comparative genomic analysis of 11 sequenced Thermoanaerobacter
      strains, including a de novo genome, Thermoanaerobacter thermohydrosulfuricus
      WC1, was conducted. Analysis was specifically focused on the genomic potential
      for each strain to address all aspects of ethanol production mentioned through a
      consolidated bioprocessing approach. Whole genome functional annotation analysis
      identified three distinct clades within the genus. The genomes of Clade 1 strains
      encode the fewest extracellular carbohydrate active enzymes and also show the
      least diversity in terms of lignocellulose relevant carbohydrate utilization
      pathways. However, these same strains reportedly are capable of directing a
      higher proportion of their total carbon flux towards ethanol, rather than non
      biofuel end-products, than other Thermoanaerobacter strains. Strains in Clade 2
      show the greatest diversity in terms of lignocellulose hydrolysis and
      utilization, but proportionately produce more non-ethanol end-products than Clade
      1 strains. Strains in Clade 3, in which T. thermohydrosulfuricus WC1 is included,
      show mid-range potential for lignocellulose hydrolysis and utilization, but also
      exhibit extensive divergence from both Clade 1 and Clade 2 strains in terms of
      cellular energetics. The potential implications regarding strain selection and
      suitability for industrial ethanol production through a consolidated
      bioprocessing co-culturing approach are examined throughout the manuscript.

PMID- 23555661
TI  - Comparative genomics of multiple strains of Pseudomonas cannabina pv.
      alisalensis, a potential model pathogen of both monocots and dicots.
AB  - Comparative genomics of closely related pathogens that differ in host range can
      provide insights into mechanisms of host-pathogen interactions and host
      adaptation. Furthermore, sequencing of multiple strains with the same host range
      reveals information concerning pathogen diversity and the molecular basis of
      virulence. Here we present a comparative analysis of draft genome sequences for
      four strains of Pseudomonas cannabina pathovar alisalensis (Pcal), which is
      pathogenic on a range of monocotyledonous and dicotyledonous plants. These draft
      genome sequences provide a foundation for understanding host range evolution
      across the monocot-dicot divide. Like other phytopathogenic pseudomonads, Pcal
      strains harboured a hrp/hrc gene cluster that codes for a type III secretion
      system. Phylogenetic analysis based on the hrp/hrc cluster genes/proteins,
      suggests localized recombination and functional divergence within the hrp/hrc
      cluster. Despite significant conservation of overall genetic content across Pcal
      genomes, comparison of type III effector repertoires reinforced previous
      molecular data suggesting the existence of two distinct lineages within this
      pathovar. Furthermore, all Pcal strains analyzed harbored two distinct genomic
      islands predicted to code for type VI secretion systems (T6SSs). While one of
      these systems was orthologous to known P. syringae T6SSs, the other more closely
      resembled a T6SS found within P. aeruginosa. In summary, our study provides a
      foundation to unravel Pcal adaptation to both monocot and dicot hosts and
      provides genetic insights into the mechanisms underlying pathogenicity.

PMID- 23555662
TI  - Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and
      Th17 T-helper cell subsets and is a direct STAT target gene.
AB  - CD4(+) T helper (Th) cells differentiate into distinct effector subsets that are
      critical for host defense, but are also implicated in the pathogenesis of
      autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as
      important drivers of multiple diseases including psoriasis, spondyloarthropathy
      and multiple sclerosis. To gain insight into the function of Th17 cells, we
      performed transcriptional profiling in hopes of elucidating products not
      previously recognized as being functionally relevant in these T cells. Herein, we
      demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted
      protein with pleiotropic effects on cellular growth, survival and integrity of
      the extracellular matrix, is preferentially produced by Th17 and Th1 cells. We
      further show that Th1 and Th17 cell TIMP1 regulation follows separate mechanisms
      with a requirement for STAT4 in the former and STAT3 in the latter. Finally, we
      demonstrate that when restricted to T cells, expression of TIMP1 promotes
      neuropathology in experimental allergic encephalomyelitis.

PMID- 23555663
TI  - Assembly and activation of alternative complement components on endothelial cell
      anchored ultra-large von Willebrand factor links complement and hemostasis
      thrombosis.
AB  - BACKGROUND: Vascular endothelial cells (ECs) express and release protein
      components of the complement pathways, as well as secreting and anchoring ultra
      large von Willebrand factor (ULVWF) multimers in long string-like structures that
      initiate platelet adhesion during hemostasis and thrombosis. The alternative
      complement pathway (AP) is an important non-antibody-requiring host defense
      system. Thrombotic microangiopathies can be associated with defective regulation
      of the AP (atypical hemolytic-uremic syndrome) or with inadequate cleavage by
      ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic
      thrombocytopenic purpura). Our goal was to determine if EC-anchored ULVWF strings
      caused the assembly and activation of AP components, thereby linking two
      essential defense mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We quantified gene
      expression of these complement components in cultured human umbilical vein
      endothelial cells (HUVECs) by real-time PCR: C3 and C5; complement factor (CF) B,
      CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not
      alternative) complement pathways. We used fluorescent microscopy, monospecific
      antibodies against complement components, fluorescent secondary antibodies, and
      the analysis of >150 images to quantify the attachment of HUVEC-released
      complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs
      (under conditions of ADAMTS-13 inhibition). We found that HUVEC-released C4 did
      not attach to ULVWF strings, ruling out activation of the classical and lectin
      pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached
      to ULVWF strings in quantitative patterns consistent with assembly of the AP
      components into active complexes. This was verified when non-functional FB
      blocked the formation of AP C3 convertase complexes (C3bBb) on ULVWF strings.
      CONCLUSIONS/SIGNIFICANCE: AP components are assembled and activated on EC
      secreted/anchored ULVWF multimeric strings. Our findings provide one possible
      molecular mechanism for clinical linkage between different types of thrombotic
      and complement-mediated disorders.

PMID- 23555664
TI  - Thermal characterization, crystal field analysis and in-band pumped laser
      performance of Er doped NaY(WO(4))(2) disordered laser crystals.
AB  - Undoped and Er-doped NaY(WO4)2 disordered single crystals have been grown by the
      Czochralski technique. The specific heat and thermal conductivity (kappa) of
      these crystals have been characterized from T = 4 K to 700 K and 360 K,
      respectively. It is shown that kappa exhibits anisotropy characteristic of single
      crystals as well as a kappa(T) behavior observed in glasses, with a saturation
      mean free phonon path of 3.6 A and 4.5 A for propagation along a and c crystal
      axes, respectively. The relative energy positions and irreducible representations
      of Stark Er(3+) levels up to (4)G(7/2) multiplet have been determined by the
      combination of experimental low (<10 K) temperature optical absorption and
      photoluminescence measurements and simulations with a single-electron Hamiltonian
      including both free-ion and crystal field interactions. Absorption, emission and
      gain cross sections of the (4)I(13/2)<->(4)I(15/2) laser related transition have
      been determined at 77 K. The (4)I(13/2) Er(3+) lifetime (tau) was measured in the
      temperature range of 77-300 K, and was found to change from tau (77K) ~ 4.5 ms to
      tau (300K) ~ 3.5 ms. Laser operation is demonstrated at 77 K and 300 K by
      resonantly pumping the (4)I(13/2) multiplet at lambda~1500 nm with a broadband
      (FWHM~20 nm) diode laser source perfectly matching the 77 K crystal (4)I(15/2) ->
      (4)I(13/2) absorption profile. At 77 K as much as 5.5 W of output power were
      obtained in pi-polarized configuration with a slope efficiency versus absorbed
      pump power of 57%, the free running laser wavelength in air was lambda~1611 nm
      with the laser output bandwidth of 3.5 nm. The laser emission was tunable over
      30.7 nm, from 1590.7 nm to 1621.4 nm, for the same pi-polarized configuration.

PMID- 23555665
TI  - Whole brain approaches for identification of microstructural abnormalities in
      individual patients: comparison of techniques applied to mild traumatic brain
      injury.
AB  - PURPOSE: Group-wise analyses of DTI in mTBI have demonstrated evidence of
      traumatic axonal injury (TAI), associated with adverse clinical outcomes.
      Although mTBI is likely to have a unique spatial pattern in each patient, group
      analyses implicitly assume that location of injury will be the same across
      patients. The purpose of this study was to optimize and validate a procedure for
      analysis of DTI images acquired in individual patients, which could detect inter
      individual differences and be applied in the clinical setting, where patients
      must be assessed as individuals. MATERIALS AND METHODS: After informed consent
      and in compliance with HIPAA, 34 mTBI patients and 42 normal subjects underwent
      3.0 Tesla DTI. Four voxelwise assessment methods (standard Z-score, "one vs.
      many" t-test, Family-Wise Error Rate control using pseudo t-distribution, EZ-MAP)
      for use in individual patients, were applied to each patient's fractional
      anisotropy (FA) maps and tested for its ability to discriminate patients from
      controls. Receiver Operating Characteristic (ROC) analyses were used to define
      optimal thresholds (voxel-level significance and spatial extent) for reliable and
      robust detection of mTBI pathology. RESULTS: ROC analyses showed EZ-MAP
      (specificity 71%, sensitivity 71%), "one vs. many" t-test and standard Z-score
      (sensitivity 65%, specificity 76% for both methods) resulted in a significant
      area under the curve (AUC) score for discriminating mTBI patients from controls
      in terms of the total number of abnormal white matter voxels detected while the
      FWER test was not significant. EZ-MAP is demonstrated to be robust to assumptions
      of Gaussian behavior and may serve as an alternative to methods that require
      strict Gaussian assumptions. CONCLUSION: EZ-MAP provides a robust approach for
      delineation of regional abnormal anisotropy in individual mTBI patients.

PMID- 23555666
TI  - The decrease of mineralcorticoid receptor drives angiogenic pathways in
      colorectal cancer.
AB  - Angiogenesis plays a crucial role in tumor growth and progression. Low expression
      of mineralocorticoid receptor (MR) in several malignant tumors correlates with
      disease recurrence and overall survival. Previous studies have shown that MR
      expression is decreased in colorectal cancer (CRC). Here we hypothesize that
      decreased MR expression can contribute to angiogenesis and poor patient survival
      in colorectal malignancies. In a cohort of CRC patients, we analyzed tumor MR
      expression, its correlation with tumor microvascular density and its impact on
      survival. Subsequently, we interrogated the role of MR in angiogenesis in an in
      vitro model, based on the colon cancer cell line HCT116, ingenierized to re
      express a physiologically controlled MR. In CRC, decreased MR expression was
      associated with increased microvascular density and poor patient survival. In
      pchMR transfected HCT116, aldosterone or natural serum steroids largely inhibited
      mRNA expression levels of both VEGFA and its receptor 2/KDR. In CRC, MR
      activation may significantly decrease angiogenesis by directly inhibiting
      dysregulated VEGFA and hypoxia-induced VEGFA mRNA expression. In addition, MR
      activation attenuates the expression of the VEGF receptor 2/KDR, possibly
      dampening the activation of a VEGFA/KDR dependent signaling pathway important for
      the survival of tumor cells under hypoxic conditions.

PMID- 23555667
TI  - Multiple roles of the extracellular vestibule amino acid residues in the function
      of the rat P2X4 receptor.
AB  - The binding of ATP to trimeric P2X receptors (P2XR) causes an enlargement of the
      receptor extracellular vestibule, leading to opening of the cation-selective
      transmembrane pore, but specific roles of vestibule amino acid residues in
      receptor activation have not been evaluated systematically. In this study,
      alanine or cysteine scanning mutagenesis of V47-V61 and F324-N338 sequences of
      rat P2X4R revealed that V49, Y54, Q55, F324, and G325 mutants were poorly
      responsive to ATP and trafficking was only affected by the V49 mutation. The Y54F
      and Y54W mutations, but not the Y54L mutation, rescued receptor function,
      suggesting that an aromatic residue is important at this position. Furthermore,
      the Y54A and Y54C receptor function was partially rescued by ivermectin, a
      positive allosteric modulator of P2X4R, suggesting a rightward shift in the
      potency of ATP to activate P2X4R. The Q55T, Q55N, Q55E, and Q55K mutations
      resulted in non-responsive receptors and only the Q55E mutant was ivermectin
      sensitive. The F324L, F324Y, and F324W mutations also rescued receptor function
      partially or completely, ivermectin action on channel gating was preserved in all
      mutants, and changes in ATP responsiveness correlated with the hydrophobicity and
      side chain volume of the substituent. The G325P mutant had a normal response to
      ATP, suggesting that G325 is a flexible hinge. A topological analysis revealed
      that the G325 and F324 residues disrupt a beta-sheet upon ATP binding. These
      results indicate multiple roles of the extracellular vestibule amino acid
      residues in the P2X4R function: the V49 residue is important for receptor
      trafficking to plasma membrane, the Y54 and Q55 residues play a critical role in
      channel gating and the F324 and G325 residues are critical for vestibule
      widening.

PMID- 23555668
TI  - Prevalence of heterotypic tumor/immune cell-in-cell structure in vitro and in
      vivo leading to formation of aneuploidy.
AB  - Cell-in-cell structures refer to a unique phenomenon that one living cell enters
      into another living cell intactly, occurring between homotypic tumor cells or
      tumor (or other tissue cells) and immune cells (named as heterotypic cell-in-cell
      structure). In the present study, through a large scale of survey we observed
      that heterotypic cell-in-cell structure formation occurred commonly in vitro with
      host cells derived from different human carcinomas as well as xenotypic mouse
      tumor cell lines. Most of the lineages of human immune cells, including T, B, NK
      cells, monocytes as well as in vitro activated LAK cells, were able to invade
      tumor cell lines. Poorly differentiated stem cells were capable of internalizing
      immune cells as well. More significantly, heterotypic tumor/immune cell-in-cell
      structures were observed in a higher frequency in tumor-derived tissues than
      those in adjacent tissues. In mouse hepatitis models, heterotypic immune
      cell/hepatocyte cell-in-cell structures were also formed in a higher frequency
      than in normal controls. After in vitro culture, different forms of internalized
      immune cells in heterotypic cell-in-cell structures were observed, with one or
      multiple immune cells inside host cells undergoing resting, degradation or
      mitosis. More strikingly, some internalized immune cells penetrated directly into
      the nucleus of target cells. Multinuclear cells with aneuploid nucleus were
      formed in target tumor cells after internalizing immune cells as well as in situ
      tumor regions. Therefore, with the prevalence of heterotypic cell-in-cell
      structures observed, we suggest that shielding of immune cells inside tumor or
      inflammatory tissue cells implies the formation of aneuploidy with the increased
      multinucleation as well as fine-tuning of microenvironment under pathological
      status, which may define distinct mechanisms to influence the etiology and
      progress of tumors.

PMID- 23555669
TI  - Computer-assisted photo identification outperforms visible implant elastomers in
      an endangered salamander, Eurycea tonkawae.
AB  - Despite recognition that nearly one-third of the 6300 amphibian species are
      threatened with extinction, our understanding of the general ecology and
      population status of many amphibians is relatively poor. A widely-used method for
      monitoring amphibians involves injecting captured individuals with unique
      combinations of colored visible implant elastomer (VIE). We compared VIE
      identification to a less-invasive method - computer-assisted photographic
      identification (photoID) - in endangered Jollyville Plateau salamanders (Eurycea
      tonkawae), a species with a known range limited to eight stream drainages in
      central Texas. We based photoID on the unique pigmentation patterns on the dorsal
      head region of 1215 individual salamanders using identification software Wild-ID.
      We compared the performance of photoID methods to VIEs using both 'high-quality'
      and 'low-quality' images, which were taken using two different camera types and
      technologies. For high-quality images, the photoID method had a false rejection
      rate of 0.76% compared to 1.90% for VIEs. Using a comparable dataset of lower
      quality images, the false rejection rate was much higher (15.9%). Photo matching
      scores were negatively correlated with time between captures, suggesting that
      evolving natural marks could increase misidentification rates in longer term
      capture-recapture studies. Our study demonstrates the utility of large-scale
      capture-recapture using photo identification methods for Eurycea and other
      species with stable natural marks that can be reliably photographed.

PMID- 23555671
TI  - Face recognition using sparse representation-based classification on k-nearest
      subspace.
AB  - The sparse representation-based classification (SRC) has been proven to be a
      robust face recognition method. However, its computational complexity is very
      high due to solving a complex l(1)-minimization problem. To improve the
      calculation efficiency, we propose a novel face recognition method, called sparse
      representation-based classification on k-nearest subspace (SRC-KNS). Our method
      first exploits the distance between the test image and the subspace of each
      individual class to determine the k nearest subspaces and then performs SRC on
      the k selected classes. Actually, SRC-KNS is able to reduce the scale of the
      sparse representation problem greatly and the computation to determine the k
      nearest subspaces is quite simple. Therefore, SRC-KNS has a much lower
      computational complexity than the original SRC. In order to well recognize the
      occluded face images, we propose the modular SRC-KNS. For this modular method,
      face images are partitioned into a number of blocks first and then we propose an
      indicator to remove the contaminated blocks and choose the k nearest subspaces.
      Finally, SRC is used to classify the occluded test sample in the new feature
      space. Compared to the approach used in the original SRC work, our modular SRC
      KNS can greatly reduce the computational load. A number of face recognition
      experiments show that our methods have five times speed-up at least compared to
      the original SRC, while achieving comparable or even better recognition rates.

PMID- 23555670
TI  - Association of cerebral networks in resting state with sexual preference of
      homosexual men: a study of regional homogeneity and functional connectivity.
AB  - Recent imaging studies have shown that brain morphology and neural activity
      during sexual arousal differ between homosexual and heterosexual men. However,
      functional differences in neural networks at the resting state is unknown. The
      study is to characterize the association of homosexual preference with measures
      of regional homogeneity and functional connectivity in the resting state.
      Participants were 26 healthy homosexual men and 26 age-matched healthy
      heterosexual men in whom we collected echo planar magnetic resonance imaging data
      in the resting state. The sexual orientation was evaluated using the Kinsey
      Scale. We first assessed group differences in regional homogeneity and then,
      taking the identified differences as seed regions, we compared groups in measures
      of functional connectivity from those seeds. The behavioral significances of the
      differences in regional homogeneity and functional connectivity were assessed by
      examining their associations with Kinsey Scores. Homosexual participants showed
      significantly reduced regional homogeneity in the left inferior occipital gyrus,
      right middle occipital gyrus, right superior occipital gyrus, left cuneus, right
      precuneus, and increased regional homogeneity in rectal gyrus, bilateral
      midbrain, and left temporal lobe. Regional homogeneity correlated positively with
      Kinsey scores in the left inferior occipital gyrus. The homosexual group also
      showed reduced functional connectivity between left middle temporal gyrus, left
      supra-marginal gyrus, right cuneus and the seed region, i.e. left inferior
      occipital gyrus. Additionly, the connection between the left inferior occipital
      gyrus and right thalamus correlated positively with Kinsey scores. These
      differences in regional homogeneity and functional connectivity may contribute to
      a better understanding of the neural basis of male sexual orientation.

PMID- 23555672
TI  - TcVac3 induced control of Trypanosoma cruzi infection and chronic myocarditis in
      mice.
AB  - We characterized the immune responses elicited by a DNA-prime/MVA-boost vaccine
      (TcVac3) constituted of antigenic candidates (TcG2 and TcG4), shown to be
      recognized by B and T cell responses in Trypanosoma cruzi (Tc) infected multiple
      hosts. C57BL/6 mice immunized with TcVac3 elicited a strong antigen-specific,
      high-avidity, trypanolytic antibody response (IgG2b>IgG1); and a robust antigen-
      and Tc-specific CD8(+)T cell response with type-1 cytokine (IFN-gamma(+)TNF
      alpha>IL-4(+)IL-10) and cytolytic effector (CD8(+)CD107a(+)IFN
      gamma(+)Perforin(+)) phenotype. The vaccine-induced effector T cells
      significantly expanded upon challenge infection and provided >92% control of T.
      cruzi. Co-delivery of IL-12 and GMCSF cytokine adjuvants didn't enhance the
      TcVac3-induced resistance to T. cruzi. In chronic phase, vaccinated/infected mice
      exhibited a significant decline (up to 70%) in IFN-gamma(+)CD8(+)T cells, a
      predominance of immunoregulatory IL-10(+)/CD4(+)T and IL10(+)/CD8(+)T cells, and
      presented undetectable tissue parasitism, inflammatory infiltrate, and fibrosis
      in vaccinated/infected mice. In comparison, control mice responded to challenge
      infection by a low antibody response, mixed cytokine profile, and consistent
      activation of pro-inflammatory CD8(+)T cells associated with parasite persistence
      and pathologic damage in the heart. We conclude that TcVac3 elicited type-1
      effector T cell immunity that effectively controlled T. cruzi infection, and
      subsequently, predominance of anti-inflammatory responses prevented chronic
      inflammation and myocarditis in chagasic mice.

PMID- 23555674
TI  - The influence of electric field and confinement on cell motility.
AB  - The ability of cells to sense and respond to endogenous electric fields is
      important in processes such as wound healing, development, and nerve
      regeneration. In cell culture, many epithelial and endothelial cell types respond
      to an electric field of magnitude similar to endogenous electric fields by moving
      preferentially either parallel or antiparallel to the field vector, a process
      known as galvanotaxis. Here we report on the influence of dc electric field and
      confinement on the motility of fibroblast cells using a chip-based platform. From
      analysis of cell paths we show that the influence of electric field on motility
      is much more complex than simply imposing a directional bias towards the cathode
      or anode. The cell velocity, directedness, as well as the parallel and
      perpendicular components of the segments along the cell path are dependent on the
      magnitude of the electric field. Forces in the directions perpendicular and
      parallel to the electric field are in competition with one another in a voltage
      dependent manner, which ultimately govern the trajectories of the cells in the
      presence of an electric field. To further investigate the effects of cell
      reorientation in the presence of a field, cells are confined within microchannels
      to physically prohibit the alignment seen in 2D environment. Interestingly, we
      found that confinement results in an increase in cell velocity both in the
      absence and presence of an electric field compared to migration in 2D.

PMID- 23555673
TI  - White matter changes in patients with amnestic mild cognitive impairment detected
      by diffusion tensor imaging.
AB  - Compared to normal aging adults, individuals with amnestic mild cognitive
      impairment (aMCI) have significantly increased risk for progressing into
      Alzheimer's disease (AD). Autopsy studies found that most of the brains of aMCI
      cases showed anatomical features associated with AD pathology. The recent
      development of non-invasive neuroimaging technique, such as diffusion tensor
      imaging (DTI), makes it possible to investigate the microstructures of the
      cerebral white matter in vivo. We hypothesized that disrupted white matter (WM)
      integrity existed in aMCI. So we used DTI technique, by measuring fractional
      anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved
      in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and
      28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole
      brain FA and MD images in each individual and group comparisons were carried out.
      Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the
      association and projection fibers of frontal, parietal, and temporal lobes,
      corpus callosum, bilateral corona radiation, right posterior thalamic radiation
      and right sagittal stratum. aMCI patients also showed significantly increased MD
      widespreadly in the association and projection fibers of frontal, parietal and
      temporal lobes, and corpus callosum. Assessment of the WM integrity of the
      frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may
      aid early diagnosis of aMCI.

PMID- 23555675
TI  - Melanin concentration gradients in modern and fossil feathers.
AB  - In birds and feathered non-avian dinosaurs, within-feather pigmentation patterns
      range from discrete spots and stripes to more subtle patterns, but the latter
      remain largely unstudied. A ~55 million year old fossil contour feather with a
      dark distal tip grading into a lighter base was recovered from the Fur Formation
      in Denmark. SEM and synchrotron-based trace metal mapping confirmed that this
      gradient was caused by differential concentration of melanin. To assess the
      potential ecological and phylogenetic prevalence of this pattern, we evaluated
      321 modern samples from 18 orders within Aves. We observed that the pattern was
      found most frequently in distantly related groups that share aquatic ecologies
      (e.g. waterfowl Anseriformes, penguins Sphenisciformes), suggesting a potential
      adaptive function with ancient origins.

PMID- 23555677
TI  - A combinatorial model of malware diffusion via bluetooth connections.
AB  - We outline here the mathematical expression of a diffusion model for cellphones
      malware transmitted through Bluetooth channels. In particular, we provide the
      deterministic formula underlying the proposed infection model, in its equivalent
      recursive (simple but computationally heavy) and closed form (more complex but
      efficiently computable) expression.

PMID- 23555676
TI  - Direct and specific effect of sevoflurane anesthesia on rat Per2 expression in
      the suprachiasmatic nucleus.
AB  - BACKGROUND: Our previous studies revealed that application of the inhalation
      anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse
      suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly
      affects the SCN. METHODS: We performed in vivo and in vitro experiments to
      investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects
      of sevoflurane on rPer2 expression were examined by quantitative in situ
      hybridization with a radioactively-labeled cRNA probe. Additionally, we examined
      the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the
      in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2
      dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2
      promoter activity. Bioluminescence from two peripheral organs, the kidney cortex
      and the anterior pituitary gland, were also analyzed. RESULTS: Application of
      sevoflurane in rats significantly suppressed Per2 expression in the SCN compared
      with untreated animals. We observed no sevoflurane-induced phase-shift in the
      rest/activity rhythms. In the in vitro experiments, the intermittent application
      of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a
      phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not
      suppress bioluminescence in the kidney cortex or the anterior pituitary gland.
      CONCLUSION: The suppression of Per2-dLuc luminescence by sevoflurane in in vitro
      SCN cultures isolated from peripheral inputs and other nuclei suggest a direct
      action of sevoflurane on the SCN itself. That sevoflurane has no such effect on
      peripheral organs suggests that this action might be mediated through a neuron
      specific cellular mechanism or a regulation of the signal transduction between
      neurons.

PMID- 23555678
TI  - Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum
      KY1032 in diet-induced obese mice is associated with gut microbial changes and
      reduction in obesity.
AB  - OBJECTIVE: To investigate the functional effects of probiotic treatment on the
      gut microbiota, as well as liver and adipose gene expression in diet-induced
      obese mice. DESIGN: Male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks
      to induce obesity, and then randomized to receive HFD+probiotic (Lactobacillus
      curvatus HY7601 and Lactobacillus plantarum KY1032, n = 9) or HFD+placebo (n = 9)
      for another 10 weeks. Normal diet (ND) fed mice (n = 9) served as non-obese
      controls. RESULTS: Diet-induced obese mice treated with probiotics showed reduced
      body weight gain and fat accumulation as well as lowered plasma insulin, leptin,
      total-cholesterol and liver toxicity biomarkers. A total of 151,061
      pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564,
      5,274 and 4,464 reads for the ND, HFD+placebo and HFD+probiotic groups,
      respectively. Gut microbiota species were shared among the experimental groups
      despite the different diets and treatments. The diversity of the gut microbiota
      and its composition were significantly altered in the diet-induced obese mice and
      after probiotic treatment. We observed concurrent transcriptional changes in
      adipose tissue and the liver. In adipose tissue, pro-inflammatory genes
      (TNFalpha, IL6, IL1beta and MCP1) were down-regulated in mice receiving probiotic
      treatment. In the liver, fatty acid oxidation-related genes (PGC1alpha, CPT1,
      CPT2 and ACOX1) were up-regulated in mice receiving probiotic treatment.
      CONCLUSIONS: The gut microbiota of diet-induced obese mice appears to be
      modulated in mice receiving probiotic treatment. Probiotic treatment might reduce
      diet-induced obesity and modulate genes associated with metabolism and
      inflammation in the liver and adipose tissue.

PMID- 23555679
TI  - Promyelocytic leukemia (PML) protein plays important roles in regulating cell
      adhesion, morphology, proliferation and migration.
AB  - PML protein plays important roles in regulating cellular homeostasis. It forms
      PML nuclear bodies (PML-NBs) that act like nuclear relay stations and participate
      in many cellular functions. In this study, we have examined the proteome of mouse
      embryonic fibroblasts (MEFs) derived from normal (PML(+/+)) and PML knockout
      (PML(-/-)) mice. The aim was to identify proteins that were differentially
      expressed when MEFs were incapable of producing PML. Using comparative
      proteomics, total protein were extracted from PML(-/-) and PML(+/+) MEFs,
      resolved by two dimensional electrophoresis (2-DE) gels and the differentially
      expressed proteins identified by LC-ESI-MS/MS. Nine proteins (PML, NDRG1, CACYBP,
      CFL1, RSU1, TRIO, CTRO, ANXA4 and UBE2M) were determined to be down-regulated in
      PML(-/-) MEFs. In contrast, ten proteins (CIAPIN1, FAM50A, SUMO2 HSPB1 NSFL1C,
      PCBP2, YWHAG, STMN1, TPD52L2 and PDAP1) were found up-regulated. Many of these
      differentially expressed proteins play crucial roles in cell adhesion, migration,
      morphology and cytokinesis. The protein profiles explain why PML(-/-) and
      PML(+/+) MEFs were morphologically different. In addition, we demonstrated PML(-/
      ) MEFs were less adhesive, proliferated more extensively and migrated
      significantly slower than PML(+/+) MEFs. NDRG1, a protein that was down-regulated
      in PML(-/-) MEFs, was selected for further investigation. We determined that
      silencing NDRG1expression in PML(+/+) MEFs increased cell proliferation and
      inhibited PML expression. Since NDRG expression was suppressed in PML(-/-) MEFs,
      this may explain why these cells proliferate more extensively than PML(+/+) MEFs.
      Furthermore, silencing NDRG1expression also impaired TGF-beta1 signaling by
      inhibiting SMAD3 phosphorylation.

PMID- 23555680
TI  - Disparities in outcomes following admission for cholangitis.
AB  - INTRODUCTION: Few have examined determinants of adverse outcomes in patients
      presenting with ascending cholangitis. The objective of this study was to examine
      factors associated with in-hospital mortality, prolonged length of stay (LOS) and
      increased hospital charges (HC) in patients presenting with acute cholangitis.
      METHODS: Within the Health Care Utilization Project Nationwide Inpatient Sample
      (NIS), we focused on patients, 18 years and older, admitted to the emergency
      department with cholangitis as primary diagnosis (1998-2009). Models were fitted
      to predict likelihood of in-hospital mortality, prolonged LOS and increased HC.
      Covariates included race, day of admission, insurance status, socio-economical
      status and other patient and hospital characteristics. RESULTS: Overall, weighted
      estimates of 248,942 patients were admitted with acute cholangitis between 1998
      and 2009, of which 13,534 (5.4%) died during the admission. Multivariable
      analyses revealed that relative to Caucasian patients, African American, Hispanic
      and Asian and Pacific Islander patients were more likely to die (OR = 1.61,
      p<0.001, OR = 1.20, p = 0.01 and OR = 1.26, p = 0.008), to experience a prolonged
      LOS (OR = 1.77, p<0.001, OR = 1.30, p<0.001, 1.34, p<0.001), and to incur high HC
      (OR = 1.83, p<0.001, OR = 1.51, p<0.001, OR = 1.56, p<0.001). Moreover, Medicaid
      and Medicare patients were more likely to die (OR = 1.64, p<0.001, OR = 1.24,
      p<0.001), to experience a prolonged LOS (1.74, p<0.001, OR = 1.25, p<0.001) and
      to incur high HC (OR = 1.23, p = 0.002, OR = 1.12, p = 0.002) compared to
      privately insured patients. In subgroup analysis, there were no differences for
      Medicare patients age 65 years and over. However, those under 65, most of whom
      have disability or end stage renal disease, were more likely to experience the
      negative outcomes. CONCLUSION: Race and insurance status represent independent
      predictors of in-hospital mortality and adverse outcomes in patients presenting
      with cholangitis. Whether these disparities are due to biological predisposition
      or unequal quality of care requires further investigation. Regardless, efforts
      should be made to reduce these outcome disparities.

PMID- 23555681
TI  - Succinate dehydrogenase upregulation destabilize complex I and limits the
      lifespan of gas-1 mutant.
AB  - Many Caenorhabditis elegans mutants with dysfunctional mitochondrial electron
      transport chain are surprisingly long lived. Both short-lived (gas-1(fc21)) and
      long-lived (nuo-6(qm200)) mutants of mitochondrial complex I have been
      identified. However, it is not clear what are the pathways determining the
      difference in longevity. We show that even in a short-lived gas-1(fc21) mutant,
      many longevity assurance pathways, shown to be important for lifespan
      prolongation in long-lived mutants, are active. Beside similar dependence on
      alternative metabolic pathways, short-lived gas-1(fc21) mutants and long-lived
      nuo-6(qm200) mutants also activate hypoxia-inducible factor -1alpha (HIF-1alpha)
      stress pathway and mitochondrial unfolded protein response (UPR(mt)). The major
      difference that we detected between mutants of different longevity, is in the
      massive loss of complex I accompanied by upregulation of complex II levels, only
      in short-lived, gas-1(fc21) mutant. We show that high levels of complex II
      negatively regulate longevity in gas-1(fc21) mutant by decreasing the stability
      of complex I. Furthermore, our results demonstrate that increase in complex I
      stability, improves mitochondrial function and decreases mitochondrial stress,
      putting it inside a "window" of mitochondrial dysfunction that allows lifespan
      prolongation.

PMID- 23555682
TI  - ITS1 copy number varies among Batrachochytrium dendrobatidis strains:
      implications for qPCR estimates of infection intensity from field-collected
      amphibian skin swabs.
AB  - Genomic studies of the amphibian-killing fungus (Batrachochytrium dendrobatidis,
      [Bd]) identified three highly divergent genetic lineages, only one of which has a
      global distribution. Bd strains within these linages show variable genomic
      content due to differential loss of heterozygosity and recombination. The current
      quantitative polymerase chain reaction (qPCR) protocol to detect the fungus from
      amphibian skin swabs targets the intergenic transcribed spacer 1 (ITS1) region
      using a TaqMan fluorescent probe specific to Bd. We investigated the consequences
      of genomic differences in the quantification of ITS1 from eight distinct Bd
      strains, including representatives from North America, South America, the
      Caribbean, and Australia. To test for potential differences in amplification, we
      compared qPCR standards made from Bd zoospore counts for each strain, and showed
      that they differ significantly in amplification rates. To test potential
      mechanisms leading to strain differences in qPCR reaction parameters (slope and y
      intercept), we: a) compared standard curves from the same strains made from
      extracted Bd genomic DNA in equimolar solutions, b) quantified the number of ITS1
      copies per zoospore using a standard curve made from PCR-amplicons of the ITS1
      region, and c) cloned and sequenced PCR-amplified ITS1 regions from these same
      strains to verify the presence of the probe site in all haplotypes. We found high
      strain variability in ITS1 copy number, ranging from 10 to 144 copies per single
      zoospore. Our results indicate that genome size might explain strain differences
      in ITS1 copy number, but not ITS1 sequence variation because the probe-binding
      site and primers were conserved across all haplotypes. For standards constructed
      from uncharacterized Bd strains, we recommend the use of single ITS1 PCR
      amplicons as the absolute standard in conjunction with current quantitative
      assays to inform on copy number variation and provide universal estimates of
      pathogen zoospore loads from field-caught amphibians.

PMID- 23555683
TI  - Identifying resistance mechanisms against five tyrosine kinase inhibitors
      targeting the ERBB/RAS pathway in 45 cancer cell lines.
AB  - Because of the low overall response rates of 10-47% to targeted cancer
      therapeutics, there is an increasing need for predictive biomarkers. We aimed to
      identify genes predicting response to five already approved tyrosine kinase
      inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib,
      erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered
      doses. A resistance matrix was determined, and gene expression profiles of the
      subsets of resistant vs. sensitive cell lines were compared. Triplicate gene
      expression signatures were obtained from the caArray project. Significance
      analysis of microarrays and rank products were applied for feature selection.
      Ninety-five genes were also measured by RT-PCR. In case of four sunitinib
      resistance associated genes, the results were validated in clinical samples by
      immunohistochemistry. A list of 63 top genes associated with resistance against
      the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis
      confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3
      and RAB25) were related to sensitivity against more than three inhibitors. The
      immunohistochemical analysis of sunitinib-treated metastatic renal cell
      carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall
      survival. In summary, we determined predictive biomarkers for five tyrosine
      kinase inhibitors, and validated sunitinib resistance biomarkers by
      immunohistochemistry in an independent patient cohort.

PMID- 23555684
TI  - On the characterization and software implementation of general protein lattice
      models.
AB  - models of proteins have been widely used as a practical means to computationally
      investigate general properties of the system. In lattice models any sterically
      feasible conformation is represented as a self-avoiding walk on a lattice, and
      residue types are limited in number. So far, only two- or three-dimensional
      lattices have been used. The inspection of the neighborhood of alpha carbons in
      the core of real proteins reveals that also lattices with higher coordination
      numbers, possibly in higher dimensional spaces, can be adopted. In this paper, a
      new general parametric lattice model for simplified protein conformations is
      proposed and investigated. It is shown how the supporting software can be
      consistently designed to let algorithms that operate on protein structures be
      implemented in a lattice-agnostic way. The necessary theoretical foundations are
      developed and organically presented, pinpointing the role of the concept of main
      directions in lattice-agnostic model handling. Subsequently, the model features
      across dimensions and lattice types are explored in tests performed on benchmark
      protein sequences, using a Python implementation. Simulations give insights on
      the use of square and triangular lattices in a range of dimensions. The trend of
      potential minimum for sequences of different lengths, varying the lattice
      dimension, is uncovered. Moreover, an extensive quantitative characterization of
      the usage of the so-called "move types" is reported for the first time. The
      proposed general framework for the development of lattice models is simple yet
      complete, and an object-oriented architecture can be proficiently employed for
      the supporting software, by designing ad-hoc classes. The proposed framework
      represents a new general viewpoint that potentially subsumes a number of
      solutions previously studied. The adoption of the described model pushes to look
      at protein structure issues from a more general and essential perspective, making
      computational investigations over simplified models more straightforward as well.

PMID- 23555685
TI  - DNA ligases I and III cooperate in alternative non-homologous end-joining in
      vertebrates.
AB  - Biochemical and genetic studies suggest that vertebrates remove double-strand
      breaks (DSBs) from their genomes predominantly by two non-homologous end joining
      (NHEJ) pathways. While canonical NHEJ depends on the well characterized
      activities of DNA-dependent protein kinase (DNA-PK) and LIG4/XRCC4/XLF complexes,
      the activities and the mechanisms of the alternative, backup NHEJ are less well
      characterized. Notably, the contribution of LIG1 to alternative NHEJ remains
      conjectural and although biochemical, cytogenetic and genetic experiments
      implicate LIG3, this contribution has not been formally demonstrated. Here, we
      take advantage of the powerful genetics of the DT40 chicken B-cell system to
      delineate the roles of LIG1 and LIG3 in alternative NHEJ. Our results expand the
      functions of LIG1 to alternative NHEJ and demonstrate a remarkable ability for
      LIG3 to backup DSB repair by NHEJ in addition to its essential function in the
      mitochondria. Together with results on DNA replication, these observations
      uncover a remarkable and previously unappreciated functional flexibility and
      interchangeability between LIG1 and LIG3.

PMID- 23555686
TI  - Registration quality assessment of acupuncture clinical trials.
AB  - BACKGROUND: Registration can help with transparency of acupuncture clinical
      trials (ACTs) by making protocol information and results available to the public.
      Recently, the number of registered ACTs has increased greatly, but only a few
      researchers have focused on the quality of ACTs registration. This review
      provides the first assessment of the registration quality of ACTs and the
      baseline information for future development. METHODS: All records of ACTs
      registered in the World Health Organization (WHO) International Clinical Trials
      Registry Platform (ICTRP) were collected. Data was extracted and input to Excel
      spreadsheets. The current 20 items of the WHO Trial Registration Data Set (TRDS)
      and the special prepared items for acupuncture intervention details were used to
      assess the registration quality of ACTs. RESULTS: A total of 740 records, found
      in 11 registries, were examined. The number of registered ACTs increased rapidly
      and involved a number of different diseases. The completeness of 20 items was not
      too poor due to 16 of them had a higher reported percentage (>85%). The
      completeness of the 20 items was different among registries. For example, the
      average registration percentage of 20 items in Clinicaltrials.gov, ChiCTR, ISRCTN
      and ANZCTR were 89.6%, 92.2%, 82.4% and 91.6% respectively. Detailed information
      regarding acupuncture intervention was seriously insufficient. Among the 740
      registration records, 89.2% lacked information on the style of acupuncture, 80.8%
      did not contain details regarding the needles used, 53.5% lacked information on
      the treatment regimen and 76.2% did not give details of other interventions
      administered with acupuncture. CONCLUSIONS: The overall registration quality of
      ACTs is not high enough due to the serious lack of information on the specifics
      of acupuncture intervention. It is vital that a number of special items be set
      regarding acupuncture in order to develop a suitable system for the registration
      of ACTs.

PMID- 23555688
TI  - TNFAIP3 gene polymorphisms in a Chinese Han population with Vogt-Koyanagi-Harada
      syndrome.
AB  - BACKGROUND: This study was performed to evaluate the potential association of
      TNFAIP3 polymorphisms with Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han
      population. METHODOLOGY/PRINCIPAL FINDINGS: Five single-nucleotide polymorphisms
      (SNPs), rs10499194, rs610604, rs7753873, rs5029928 and rs9494885 of TNFAIP3 were
      genotyped in 834 VKH disease patients and 1415 healthy controls using a PCR
      restriction fragment length polymorphism assay. An increased frequency of the C
      allele and CT genotype for rs9494885 were found in VKH patients in the Guangzhou
      and Chongqing cohorts (pc = 0.015, OR = 1.6, pc = 0.036, OR = 1.7; pc = 2.36*10
      4, OR = 1.5, pc = 0.012, OR = 1.5, respectively). Meanwhile, a decreased
      frequency of the TT genotype for rs9494885 was observed in VKH patients in the
      Guangzhou and Chongqing cohorts (pc = 0.026, OR = 0.6, pc = 0.0074, OR = 0.7,
      respectively). The combined analysis showed that a significantly increased
      prevalence of the rs9494885 TC genotype and C allele were found in VKH disease
      patients compared with controls (pc = 2.26*10-5, OR = 1.7; pc = 1.09* 10-5, OR =
      1.6, respectively). The frequency of the TT genotype of rs9494885 was markedly
      lower in VKH disease patients as compared with that in controls (pc = 1.12*10-5,
      OR = 0.6; pc = 1.09*10(-5), OR = 0.6, respectively). No association was found
      between rs10499194, rs610604, rs7753873 and rs5029928 polymorphisms and VKH
      disease. To our knowledge this is the first report describing the association of
      a TNFAIP3 gene polymorphism with VKH disease in a Chinese Han population.
      CONCLUSIONS/SIGNIFICANCE: The results suggest that the rs9494885 TC genotype and
      C allele may be predisposing factors to VKH disease, whereas the rs9494885 TT
      genotype and T allele may provide protection against this disease.

PMID- 23555687
TI  - Suppressive effects of anthrax lethal toxin on megakaryopoiesis.
AB  - Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT
      challenge suppresses platelet counts and platelet function in mice, however, the
      mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular
      mitogen-activated protein kinases (MAPKs), which are vital pathways responsible
      for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2
      extracellular signal-regulated kinase pathway, is particularly important in
      megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the
      progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using
      cord blood-derived CD34(+) cells and mouse bone marrow mononuclear cells to
      perform in vitro differentiation, this work shows that LT suppresses
      megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin
      treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick
      onset of lethality in LT-challenged mice. These results suggest that
      megakaryocytic suppression is one of the mechanisms by which LT induces
      thrombocytopenia. These findings may provide new insights for developing feasible
      approaches against anthrax.

PMID- 23555689
TI  - Robust detection of rare species using environmental DNA: the importance of
      primer specificity.
AB  - Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare
      animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a
      particularly powerful tool because of the method's sensitivity, specificity, and
      potential to quantify target DNA. However, there has been little work
      understanding the performance of these assays in the presence of closely related,
      sympatric taxa. If related species cause any cross-amplification or interference,
      false positives and negatives may be generated. These errors can be disastrous if
      false positives lead to overestimate the abundance of an endangered species or if
      false negatives prevent detection of an invasive species. In this study we test
      factors that influence the specificity and sensitivity of TaqMan MGB assays using
      co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout
      (S. confluentus) as a case study. We found qPCR to be substantially more
      sensitive than traditional PCR, with a high probability of detection at
      concentrations as low as 0.5 target copies/ul. We also found that number and
      placement of base pair mismatches between the Taqman MGB assay and non-target
      templates was important to target specificity, and that specificity was most
      influenced by base pair mismatches in the primers, rather than in the probe. We
      found that insufficient specificity can result in both false positive and false
      negative results, particularly in the presence of abundant related species. Our
      results highlight the utility of qPCR as a highly sensitive eDNA tool, and
      underscore the importance of careful assay design.

PMID- 23555690
TI  - Evaluation of Pacific white shrimp (Litopenaeus vannamei) health during a
      superintensive aquaculture growout using NMR-based metabolomics.
AB  - Success of the shrimp aquaculture industry requires technological advances that
      increase production and environmental sustainability. Indoor, superintensive,
      aquaculture systems are being developed that permit year-round production of
      farmed shrimp at high densities. These systems are intended to overcome problems
      of disease susceptibility and of water quality issues from waste products, by
      operating as essentially closed systems that promote beneficial microbial
      communities (biofloc). The resulting biofloc can assimilate and detoxify wastes,
      may provide nutrition for the farmed organisms resulting in improved growth, and
      may aid in reducing disease initiated from external sources. Nuclear magnetic
      resonance (NMR)-based metabolomic techniques were used to assess shrimp health
      during a full growout cycle from the nursery phase through harvest in a minimal
      exchange, superintensive, biofloc system. Aberrant shrimp metabolomes were
      detected from a spike in total ammonia nitrogen in the nursery, from a reduced
      feeding period that was a consequence of surface scum build-up in the raceway,
      and from the stocking transition from the nursery to the growout raceway. The
      biochemical changes in the shrimp that were induced by the stressors were
      essential for survival and included nitrogen detoxification and energy
      conservation mechanisms. Inosine and trehalose may be general biomarkers of
      stress in Litopenaeus vannamei. This study demonstrates one aspect of the
      practicality of using NMR-based metabolomics to enhance the aquaculture industry
      by providing physiological insight into common environmental stresses that may
      limit growth or better explain reduced survival and production.

PMID- 23555691
TI  - Functionally cloned pdrM from Streptococcus pneumoniae encodes a Na(+) coupled
      multidrug efflux pump.
AB  - Multidrug efflux pumps play an important role as a self-defense system in
      bacteria. Bacterial multidrug efflux pumps are classified into five families
      based on structure and coupling energy: resistance-nodulation-cell division
      (RND), small multidrug resistance (SMR), major facilitator (MF), ATP binding
      cassette (ABC), and multidrug and toxic compounds extrusion (MATE). We cloned a
      gene encoding a MATE-type multidrug efflux pump from Streptococcus pneumoniae R6,
      and designated it pdrM. PdrM showed sequence similarity with NorM from Vibrio
      parahaemolyticus, YdhE from Escherichia coli, and other bacterial MATE-type
      multidrug efflux pumps. Heterologous expression of PdrM let to elevated
      resistance to several antibacterial agents, norfloxacin, acriflavine, and 4',6
      diamidino-2-phenylindole (DAPI) in E. coli KAM32 cells. PdrM effluxes acriflavine
      and DAPI in a Na(+)- or Li(+)-dependent manner. Moreover, Na(+) efflux via PdrM
      was observed when acriflavine was added to Na(+)-loaded cells expressing pdrM.
      Therefore, we conclude that PdrM is a Na(+)/drug antiporter in S. pneumoniae. In
      addition to pdrM, we found another two genes, spr1756 and spr1877,that met the
      criteria of MATE-type by searching the S. pneumoniae genome database. However,
      cloned spr1756 and spr1877 did not elevate the MIC of any of the investigated
      drugs. mRNA expression of spr1756, spr1877, and pdrM was detected in S.
      pneumoniae R6 under laboratory growth conditions. Therefore, spr1756 and spr1877
      are supposed to play physiological roles in this growth condition, but they may
      be unrelated to drug resistance.

PMID- 23555692
TI  - Diagnosing and mapping pulmonary emphysema on X-ray projection images:
      incremental value of grating-based X-ray dark-field imaging.
AB  - PURPOSE: To assess whether grating-based X-ray dark-field imaging can increase
      the sensitivity of X-ray projection images in the diagnosis of pulmonary
      emphysema and allow for a more accurate assessment of emphysema distribution.
      MATERIALS AND METHODS: Lungs from three mice with pulmonary emphysema and three
      healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray
      source. Median signal intensities of transmission (T), dark-field (V) and a
      combined parameter (normalized scatter) were compared between emphysema and
      control group. To determine the diagnostic value of each parameter in
      differentiating between healthy and emphysematous lung tissue, a receiver
      operating-characteristic (ROC) curve analysis was performed both on a per-pixel
      and a per-individual basis. Parametric maps of emphysema distribution were
      generated using transmission, dark-field and normalized scatter signal and
      correlated with histopathology. RESULTS: Transmission values relative to water
      were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06,
      p<0.001). There was no difference in median dark-field signal intensities between
      both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in
      the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the
      best parameter for differentiation of healthy vs. emphysematous lung tissue. In a
      per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter
      value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and
      dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very
      high sensitivity for a wide range of specificity values (94% sensitivity at 75%
      specificity). Using the normalized scatter signal to display the regional
      distribution of emphysema provides color-coded parametric maps, which show the
      best correlation with histopathology. CONCLUSION: In a murine model, the
      complementary information provided by X-ray transmission and dark-field images
      adds incremental diagnostic value in detecting pulmonary emphysema and
      visualizing its regional distribution as compared to conventional X-ray
      projections.

PMID- 23555693
TI  - RNAi-mediated knockdown of catalase causes cell cycle arrest in SL-1 cells and
      results in low survival rate of Spodoptera litura (Fabricius).
AB  - Deregulated reactive oxygen species (ROS) production can lead to the disruption
      of structural and functional integrity of cells as a consequence of reactive
      interaction between ROS and various biological components. Catalase (CAT) is a
      common enzyme existing in nearly all organisms exposed to oxygen, which
      decomposes harmful hydrogen peroxide, into water and oxygen. In this study, the
      full length sequence that encodes CAT-like protein from Spodoptera litura named
      siltCAT (GenBank accession number: JQ_663444) was cloned and characterized. Amino
      acid sequence alignment showed siltCAT shared relatively high conservation with
      other insect, especially the conserved residues which defined heme and NADPH
      orientation. Expression pattern analysis showed that siltCAT mRNA was mainly
      expressed in the fat body, midgut, cuticle and malpighian tube, and as well as
      over last instar larvae, pupa and adult stages. RNA interference was used to
      silence CAT gene in SL-1 cells and the fourth-instar stage of S. litura larvae
      respectively. Our results provided evidence that CAT knockdown induced ROS
      generation, cell cycle arrest and apoptosis in SL-1 cells. It also confirmed the
      decrease in survival rate because of increased ROS production in experimental
      groups injected with double-stranded RNA of CAT (dsCAT). This study implied that
      ROS scavenging by CAT is important for S. litura survival.

PMID- 23555694
TI  - Optimizing treatment regimes to hinder antiviral resistance in influenza across
      time scales.
AB  - The large-scale use of antivirals during influenza pandemics poses a significant
      selection pressure for drug-resistant pathogens to emerge and spread in a
      population. This requires treatment strategies to minimize total infections as
      well as the emergence of resistance. Here we propose a mathematical model in
      which individuals infected with wild-type influenza, if treated, can develop de
      novo resistance and further spread the resistant pathogen. Our main purpose is to
      explore the impact of two important factors influencing treatment effectiveness:
      i) the relative transmissibility of the drug-resistant strain to wild-type, and
      ii) the frequency of de novo resistance. For the endemic scenario, we find a
      condition between these two parameters that indicates whether treatment regimes
      will be most beneficial at intermediate or more extreme values (e.g., the
      fraction of infected that are treated). Moreover, we present analytical
      expressions for effective treatment regimes and provide evidence of its
      applicability across a range of modeling scenarios: endemic behavior with
      deterministic homogeneous mixing, and single-epidemic behavior with deterministic
      homogeneous mixing and stochastic heterogeneous mixing. Therefore, our results
      provide insights for the control of drug-resistance in influenza across time
      scales.

PMID- 23555695
TI  - Preadult parental diet affects offspring development and metabolism in Drosophila
      melanogaster.
AB  - When Drosophila melanogaster larvae are reared on isocaloric diets differing in
      their amounts of protein relative to sugar, emerging adults exhibit significantly
      different development times and metabolic pools of protein, glycogen and
      trigylcerides. In the current study, we show that the influence of larval diet
      experienced during just one generation extends into the next generation, even
      when that subsequent generation had been shifted to a standard diet during
      development. Offspring of flies that were reared on high protein relative to
      sugar underwent metamorphosis significantly faster, had higher reproductive
      outputs, and different metabolic pool contents compared to the offspring of
      adults from low protein relative to sugar diets. In addition, isofemale lines
      differed in the degree to which parental effects were observed, suggesting a
      genetic component to the observed transgenerational influences.

PMID- 23555696
TI  - IL-17A and IFN-gamma synergistically induce RNase 7 expression via STAT3 in
      primary keratinocytes.
AB  - Human keratinocytes produce several antimicrobial peptides and proteins (AMP)
      which contribute to the protection of human skin against infection. RNase 7 is a
      major AMP involved in cutaneous defense with a high expression in keratinocytes
      and a broad spectrum of antimicrobial activity. The cytokine IL-17A has been
      recently identified as a potent inducer of several AMP in keratinocytes. Since
      the role of IL-17A to induce RNase 7 expression is unknown we analyzed IL-17A
      alone and in combination with other cytokines to induce RNase 7 expression in
      keratinocytes. Whereas IL-17A alone only weakly induced RNase 7 expression, the
      synergistic combination of IL-17A and IFN-gamma (IL-17A/IFN-gamma) was identified
      as a potent inducer of RNase 7 expression. This combination was more effective in
      inducing RNase 7 than the combination of IL-17A/TNF-alpha, a combination
      previously identified as a strong inducer of psoriasis-related immune response
      genes including several AMP. IFN-gamma and IL-17A both have been reported to
      activate the transcription factor STAT3 (Signal transducer and activator of
      transcription 3). Therefore we investigated the influence of STAT3 on the IL
      17A/IFN-gamma -mediated RNase 7 induction. The use of a STAT3 inhibitor as well
      as siRNA-mediated downregulation of STAT3 resulted in a diminished IL-17A/IFN
      gamma -mediated RNase 7 induction in keratinocytes indicating that STAT3 is
      involved in this process. Similarly as seen with RNase 7, treatment of
      keratinocytes with IL-17A/IFN-gamma revealed also a synergistic induction of gene
      expression of the AMP human beta-defensin (hBD)-2 and -3 as well as the S100
      protein psoriasin (S100A7) indicating that the combination of IL-17A/IFN-gamma is
      a potent inducer of various AMP classes in general. This was also reflected by an
      increase of the Staphylococcus aureus-killing activity of IL-17A/IFN-gamma 
      treated keratinocytes.

PMID- 23555697
TI  - Bmp and Shh signaling mediate the expression of satb2 in the pharyngeal arches.
AB  - In human, mutation of the transcription factor SATB2 causes severe defects to the
      palate and jaw. The expression and sequence of SATB2 is highly conserved across
      vertebrate species, including zebrafish. We sought to understand the regulation
      of satb2 using the zebrafish model system. Due to the normal expression domains
      of satb2, we analyzed satb2 expression in mutants with disrupted Hh signaling or
      defective ventral patterning. While satb2 expression appears independent of Edn1
      signaling, appropriate expression requires Shha, Smo, Smad5 and Hand2 function.
      Transplantation experiments show that neural crest cells receive both Bmp and Hh
      signaling to induce satb2 expression. Dorsomorphin- and cyclopamine-mediated
      inhibition of Bmp and Hh signaling, respectively, suggests that proper satb2
      expression requires a relatively earlier Bmp signal and a later Hh signal. We
      propose that Bmp signaling establishes competence for the neural crest to respond
      to Hh signaling, thus inducing satb2 expression.

PMID- 23555699
TI  - Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts:
      a novel high-precision approach.
AB  - Orthotopic bladder cancer xenografts are essential for testing novel therapies
      and molecular manipulations of cell lines in vivo. Current xenografts rely on
      tumor cell inoculation by intravesical instillation or direct injection into the
      bladder wall. Instillation is limited by the lack of cell lines that are
      tumorigenic when delivered in this manner. The invasive model inflicts morbidity
      on the mice by the need for laparotomy and mobilization of the bladder.
      Furthermore this procedure is complex and time-consuming. Three bladder cancer
      cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by
      percutaneous injection under ultrasound guidance. PBS was first injected between
      the muscle wall and the mucosa to separate these layers, and tumor cells were
      subsequently injected into this space. Bioluminescence and ultrasound were used
      to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes
      in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate
      proof of principle that therapeutic agents can be injected into established
      xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM
      UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23-37
      days. Percutaneous injection of tumor cells into the bladder wall was performed
      efficiently (mean time: 5.7 min) and without complications in all 50 animals.
      Ultrasound and bioluminescence confirmed presence of tumor in the anterior
      bladder wall in all animals 3 days later. The average tumor volumes increased
      steadily over the study period. UM-UC13 tumors showed a marked decrease in volume
      and perfusion after chemotherapy. Immunohistochemical staining for VSV-G
      demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We
      have developed a novel method for creating orthotopic bladder cancer xenograft in
      a minimally invasive fashion. In our hands this has replaced the traditional
      model requiring laparotomy, because this model is more time efficient, more
      precise and associated with less morbidity for the mice.

PMID- 23555698
TI  - De novo transcriptome sequence assembly and analysis of RNA silencing genes of
      Nicotiana benthamiana.
AB  - BACKGROUND: Nicotiana benthamiana has been widely used for transient gene
      expression assays and as a model plant in the study of plant-microbe
      interactions, lipid engineering and RNA silencing pathways. Assembling the
      sequence of its transcriptome provides information that, in conjunction with the
      genome sequence, will facilitate gaining insight into the plant's capacity for
      high-level transient transgene expression, generation of mobile gene silencing
      signals, and hyper-susceptibility to viral infection. METHODOLOGY/RESULTS: RNA
      seq libraries from 9 different tissues were deep sequenced and assembled, de
      novo, into a representation of the transcriptome. The assembly, of 16GB of
      sequence, yielded 237,340 contigs, clustering into 119,014 transcripts
      (unigenes). Between 80 and 85% of reads from all tissues could be mapped back to
      the full transcriptome. Approximately 63% of the unigenes exhibited a match to
      the Solgenomics tomato predicted proteins database. Approximately 94% of the
      Solgenomics N. benthamiana unigene set (16,024 sequences) matched our unigene set
      (119,014 sequences). Using homology searches we identified 31 homologues that are
      involved in RNAi-associated pathways in Arabidopsis thaliana, and show that they
      possess the domains characteristic of these proteins. Of these genes, the RNA
      dependent RNA polymerase gene, Rdr1, is transcribed but has a 72 nt insertion in
      exon1 that would cause premature termination of translation. Dicer-like 3 (DCL3)
      appears to lack both the DEAD helicase motif and second dsRNA binding motif, and
      DCL2 and AGO4b have unexpectedly high levels of transcription. CONCLUSIONS: The
      assembled and annotated representation of the transcriptome and list of RNAi
      associated sequences are accessible at www.benthgenome.com alongside a draft
      genome assembly. These genomic resources will be very useful for further study of
      the developmental, metabolic and defense pathways of N. benthamiana and in
      understanding the mechanisms behind the features which have made it such a well
      used model plant.

PMID- 23555700
TI  - Copper deficiency leads to anemia, duodenal hypoxia, upregulation of HIF-2alpha
      and altered expression of iron absorption genes in mice.
AB  - Iron and copper are essential trace metals, actively absorbed from the proximal
      gut in a regulated fashion. Depletion of either metal can lead to anemia. In the
      gut, copper deficiency can affect iron absorption through modulating the activity
      of hephaestin - a multi-copper oxidase required for optimal iron export from
      enterocytes. How systemic copper status regulates iron absorption is unknown.
      Mice were subjected to a nutritional copper deficiency-induced anemia regime from
      birth and injected with copper sulphate intraperitoneally to correct the anemia.
      Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia
      inducible factor 2alpha (HIF-2alpha) levels, a regulator of iron absorption. HIF
      2alpha upregulation in copper deficiency appeared to be independent of duodenal
      iron or copper levels and correlated with the expression of iron transporters
      (Ferroportin - Fpn, Divalent Metal transporter - Dmt1) and ferric reductase -
      Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper
      injection resulted in down regulation of HIF-2alpha-regulated iron absorption
      genes in the gut. Our work identifies HIF-2alpha as an important regulator of
      iron transport machinery in copper deficiency.

PMID- 23555701
TI  - Inhibition of ice growth and recrystallization by zirconium acetate and zirconium
      acetate hydroxide.
AB  - The control over ice crystal growth, melting, and shaping is important in a
      variety of fields, including cell and food preservation and ice templating for
      the production of composite materials. Control over ice growth remains a
      challenge in industry, and the demand for new cryoprotectants is high. Naturally
      occurring cryoprotectants, such as antifreeze proteins (AFPs), present one
      solution for modulating ice crystal growth; however, the production of AFPs is
      expensive and inefficient. These obstacles can be overcome by identifying
      synthetic substitutes with similar AFP properties. Zirconium acetate (ZRA) was
      recently found to induce the formation of hexagonal cavities in materials
      prepared by ice templating. Here, we continue this line of study and examine the
      effects of ZRA and a related compound, zirconium acetate hydroxide (ZRAH), on ice
      growth, shaping, and recrystallization. We found that the growth rate of ice
      crystals was significantly reduced in the presence of ZRA and ZRAH, and that
      solutions containing these compounds display a small degree of thermal
      hysteresis, depending on the solution pH. The compounds were found to inhibit
      recrystallization in a manner similar to that observed in the presence of AFPs.
      The favorable properties of ZRA and ZRAH suggest tremendous potential utility in
      industrial applications.

PMID- 23555702
TI  - Boron stress responsive microRNAs and their targets in barley.
AB  - Boron stress is an environmental factor affecting plant development and
      production. Recently, microRNAs (miRNAs) have been found to be involved in
      several plant processes such as growth regulation and stress responses. In this
      study, miRNAs associated with boron stress were identified and characterized in
      barley. miRNA profiles were also comparatively analyzed between root and leave
      samples. A total of 31 known and 3 new miRNAs were identified in barley; 25 of
      them were found to respond to boron treatment. Several miRNAs were expressed in a
      tissue specific manner; for example, miR156d, miR171a, miR397, and miR444a were
      only detected in leaves. Additionally, a total of 934 barley transcripts were
      found to be specifically targeted and degraded by miRNAs. In silico analysis of
      miRNA target genes demonstrated that many miRNA targets are conserved
      transcription factors such as Squamosa promoter-binding protein, Auxin response
      factor (ARF), and the MYB transcription factor family. A majority of these
      targets were responsible for plant growth and response to environmental changes.
      We also propose that some of the miRNAs in barley such as miRNA408 might play
      critical roles against boron exposure. In conclusion, barley may use several
      pathways and cellular processes targeted by miRNAs to cope with boron stress.

PMID- 23555703
TI  - Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral
      olfactory responses in rats.
AB  - A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome
      P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in
      mammalian olfactory mucosa (OM). These enzymes are known to catalyze the
      biotransformation of exogenous compounds to facilitate elimination. However, the
      functions of these enzymes in the olfactory epithelium are not clearly
      understood. In addition to protecting against inhaled toxic compounds, these
      enzymes could also metabolize odorant molecules, and thus modify their
      stimulating properties or inactivate them. In the present study, we investigated
      the in vitro biotransformation of odorant molecules in the rat OM and assessed
      the impact of this metabolism on peripheral olfactory responses. Rat OM was found
      to efficiently metabolize quinoline, coumarin and isoamyl acetate. Quinoline and
      coumarin are metabolized by CYPs whereas isoamyl acetate is hydrolyzed by
      carboxylesterases. Electro-olfactogram (EOG) recordings revealed that the
      hydroxylated metabolites derived from these odorants elicited lower olfactory
      response amplitudes than the parent molecules. We also observed that glucurono
      conjugated derivatives induced no olfactory signal. Furthermore, we demonstrated
      that the local application of a CYP inhibitor on rat olfactory epithelium
      increased EOG responses elicited by quinoline and coumarin. Similarly, the
      application of a carboxylesterase inhibitor increased the EOG response elicited
      by isoamyl acetate. This increase in EOG amplitude provoked by XME inhibitors is
      likely due to enhanced olfactory sensory neuron activation in response to odorant
      accumulation. Taken together, these findings strongly suggest that
      biotransformation of odorant molecules by enzymes localized to the olfactory
      mucosa may change the odorant's stimulating properties and may facilitate the
      clearance of odorants to avoid receptor saturation.

PMID- 23555704
TI  - Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic
      review.
AB  - BACKGROUND: Recent studies suggest certain antiretroviral therapy (ART) drugs are
      associated with increases in cardiovascular disease. PURPOSE: We performed a
      systematic review and meta-analysis to summarize the available evidence, with the
      goal of elucidating whether specific ART drugs are associated with an increased
      risk of myocardial infarction (MI). DATA SOURCES: We searched Medline, Web of
      Science, the Cochrane Library, and abstract archives from the Conference on
      Retroviruses and Opportunistic Infections and International AIDS Society up to
      June 2011 to identify published articles and abstracts. STUDY SELECTION: Eligible
      studies were comparative and included MI, strokes, or other cardiovascular events
      as outcomes. DATA EXTRACTION: Eligibility screening, data extraction, and quality
      assessment were performed independently by two investigators. DATA SYNTHESIS:
      Random effects methods and Fisher's combined probability test were used to
      summarize evidence. FINDINGS: Twenty-seven studies met inclusion criteria, with 8
      contributing to a formal meta-analysis. Findings based on two observational
      studies indicated an increase in risk of MI for patients recently exposed
      (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51-2.42)
      and protease inhibitors (PI) (RR 2.13, 95% CI 1.06-4.28). Our analysis also
      suggested an increased risk associated with each additional year of exposure to
      indinavir (RR 1.11, 95% CI 1.05-1.17) and lopinavir (RR 1.22, 95% CI 1.01-1.47).
      Our findings of increased cardiovascular risk from abacavir and PIs were in
      contrast to four published meta-analyses based on secondary analyses of
      randomized controlled trials, which found no increased risk from cardiovascular
      disease. CONCLUSION: Although observational studies implicated specific drugs,
      the evidence is mixed. Further, meta-analyses of randomized trials did not find
      increased risk from abacavir and PIs. Our findings that implicate specific ARTs
      in the observational setting provide sufficient evidence to warrant further
      investigation of this relationship in studies designed for that purpose.

PMID- 23555705
TI  - Differential mechanisms associated with vascular disrupting action of
      electrochemotherapy: intravital microscopy on the level of single normal and
      tumor blood vessels.
AB  - Electropermeabilization/electroporation (EP) provides a tool for the introduction
      of molecules into cells and tissues. In electrochemotherapy (ECT), cytotoxic
      drugs are introduced into cells in tumors, and nucleic acids are introduced into
      cells in gene electrotransfer. The normal and tumor tissue blood flow modifying
      effects of EP and the vascular disrupting effect of ECT in tumors have already
      been determined. However, differential effects between normal vs. tumor vessels,
      to ensure safety in the clinical application of ECT, have not been determined
      yet. Therefore, the aim of our study was to determine the effects of EP and ECT
      with bleomycin on the HT-29 human colon carcinoma tumor model and its surrounding
      blood vessels. The response of blood vessels to EP and ECT was monitored in real
      time, directly at the single blood vessel level, by in vivo optical imaging in a
      dorsal window chamber in SCID mice with 70 kDa fluorescently labeled dextrans.
      The response of tumor blood vessels to EP and ECT started to differ within the
      first hour. Both therapies induced a vascular lock, decreased functional vascular
      density (FVD) and increased the diameter of functional blood vessels within the
      tumor. The effects were more pronounced for ECT, which destroyed the tumor blood
      vessels within 24 h. Although the vasculature surrounding the tumor was affected
      by EP and ECT, it remained functional. The study confirms the current model of
      tumor blood flow modifying effects of EP and provides conclusive evidence that
      ECT is a vascular disrupting therapy with a specific effect on the tumor blood
      vessels.

PMID- 23555706
TI  - Psychiatric diagnosis revisited: towards a system of staging and profiling
      combining nomothetic and idiographic parameters of momentary mental states.
AB  - BACKGROUND: Mental disorders may be reducible to sets of symptoms, connected
      through systems of causal relations. A clinical staging model predicts that in
      earlier stages of illness, symptom expression is both non-specific and diffuse.
      With illness progression, more specific syndromes emerge. This paper addressed
      the hypothesis that connection strength and connection variability between mental
      states differ in the hypothesized direction across different stages of
      psychopathology. METHODS: In a general population sample of female siblings
      (mostly twins), the Experience Sampling Method was used to collect repeated
      measures of three momentary mental states (positive affect, negative affect and
      paranoia). Staging was operationalized across four levels of increasing severity
      of psychopathology, based on the total score of the Symptom Check List.
      Multilevel random regression was used to calculate inter- and intra-mental state
      connection strength and connection variability over time by modelling each
      momentary mental state at t as a function of the three momentary states at t-1,
      and by examining moderation by SCL-severity. RESULTS: Mental states impacted
      dynamically on each other over time, in interaction with SCL-severity groups.
      Thus, SCL-90 severity groups were characterized by progressively greater inter-
      and intra-mental state connection strength, and greater inter- and intra-mental
      state connection variability. CONCLUSION: Diagnosis in psychiatry can be
      described as stages of growing dynamic causal impact of mental states over time.
      This system achieves a mode of psychiatric diagnosis that combines nomothetic
      (group-based classification across stages) and idiographic (individual-specific
      psychopathological profiles) components of psychopathology at the level of
      momentary mental states impacting on each other over time.

PMID- 23555707
TI  - Robustness of Helicobacter pylori infection conferred by context-variable
      redundancy among cysteine-rich paralogs.
AB  - Deletion of single genes from expanded gene families in bacterial genomes often
      does not elicit a phenotype thus implying redundancy or functional non
      essentiality of paralogous genes. The molecular mechanisms that facilitate
      evolutionary maintenance of such paralogs despite selective pressures against
      redundancy remain mostly unexplored. Here, we investigate the evolutionary,
      genetic, and functional interaction between the Helicobacter pylori cysteine-rich
      paralogs hcpG and hcpC in the context of H. pylori infection of cultured
      mammalian cells. We find that in natural H. pylori populations both hcpG and hcpC
      are maintained by positive selection in a dual genetic relationship that switches
      from complete redundancy during early infection, whereby DeltahcpC or DeltahcpG
      mutants themselves show no growth defect but a significant growth defect is seen
      in the DeltahcpC,DeltahcpG double mutant, to quantitative redundancy during late
      infection wherein the growth defect of the DeltahcpC mutant is exacerbated in the
      DeltahcpC,DeltahcpG double mutant although the DeltahcpG mutant itself shows no
      defect. Moreover, during early infection both hcpG and hcpC are essential for
      optimal translocation of the H. pylori HspB/GroEL chaperone, but during middle-to
      late infection hcpC alone is necessary and sufficient for HspB/GroEL
      translocation thereby revealing the lack of functional compensation among
      paralogs. We propose that evolution of context-dependent differences in the
      nature of genetic redundancy, and function, between hcpG and hcpC may facilitate
      their maintenance in H. pylori genomes, and confer robustness to H. pylori growth
      during infection of cultured mammalian cells.

PMID- 23555708
TI  - Genome-wide characterization and linkage mapping of simple sequence repeats in
      mei (Prunus mume Sieb. et Zucc.).
AB  - Because of its popularity as an ornamental plant in East Asia, mei (Prunus mume
      Sieb. et Zucc.) has received increasing attention in genetic and genomic research
      with the recent shotgun sequencing of its genome. Here, we performed the genome
      wide characterization of simple sequence repeats (SSRs) in the mei genome and
      detected a total of 188,149 SSRs occurring at a frequency of 794 SSR/Mb.
      Mononucleotide repeats were the most common type of SSR in genomic regions,
      followed by di- and tetranucleotide repeats. Most of the SSRs in coding sequences
      (CDS) were composed of tri- or hexanucleotide repeat motifs, but mononucleotide
      repeats were always the most common in intergenic regions. Genome-wide comparison
      of SSR patterns among the mei, strawberry (Fragaria vesca), and apple
      (Malus*domestica) genomes showed mei to have the highest density of SSRs,
      slightly higher than that of strawberry (608 SSR/Mb) and almost twice as high as
      that of apple (398 SSR/Mb). Mononucleotide repeats were the dominant SSR motifs
      in the three Rosaceae species. Using 144 SSR markers, we constructed a 670 cM
      long linkage map of mei delimited into eight linkage groups (LGs), with an
      average marker distance of 5 cM. Seventy one scaffolds covering about 27.9% of
      the assembled mei genome were anchored to the genetic map, depending on which the
      macro-colinearity between the mei genome and Prunus T*E reference map was
      identified. The framework map of mei constructed provides a first step into
      subsequent high-resolution genetic mapping and marker-assisted selection for this
      ornamental species.

PMID- 23555709
TI  - Picomonas judraskeda gen. et sp. nov.: the first identified member of the Picozoa
      phylum nov., a widespread group of picoeukaryotes, formerly known as
      'picobiliphytes'.
AB  - In 2007, a novel, putatively photosynthetic picoeukaryotic lineage, the
      'picobiliphytes', with no known close eukaryotic relatives, was reported from 18S
      environmental clone library sequences and fluorescence in situ hybridization.
      Although single cell genomics later showed these organisms to be heterotrophic
      rather than photosynthetic, until now this apparently widespread group of pico
      (or nano-)eukaryotes has remained uncultured and the organisms could not be
      formally recognized. Here, we describe Picomonas judraskeda gen. et sp. nov.,
      from marine coastal surface waters, which has a 'picobiliphyte' 18S rDNA
      signature. Using vital mitochondrial staining and cell sorting by flow cytometry,
      a single cell-derived culture was established. The cells are biflagellate, 2.5
      3.8*2-2.5 um in size, lack plastids and display a novel stereotypic cycle of cell
      motility (described as the "jump, drag, and skedaddle"-cycle). They consist of
      two hemispherical parts separated by a deep cleft, an anterior part that contains
      all major cell organelles including the flagellar apparatus, and a posterior part
      housing vacuoles/vesicles and the feeding apparatus, both parts separated by a
      large vacuolar cisterna. From serial section analyses of cells, fixed at putative
      stages of the feeding cycle, it is concluded that cells are not bacterivorous,
      but feed on small marine colloids of less than 150 nm diameter by fluid-phase,
      bulk flow endocytosis. Based on the novel features of cell motility,
      ultrastructure and feeding, and their isolated phylogenetic position, we
      establish a new phylum, Picozoa, for Picomonas judraskeda, representing an
      apparently widespread and ecologically important group of heterotrophic
      picoeukaryotes, formerly known as 'picobiliphytes'.

PMID- 23555711
TI  - Automated transmission-mode scanning electron microscopy (tSEM) for large volume
      analysis at nanoscale resolution.
AB  - Transmission-mode scanning electron microscopy (tSEM) on a field emission SEM
      platform was developed for efficient and cost-effective imaging of circuit-scale
      volumes from brain at nanoscale resolution. Image area was maximized while
      optimizing the resolution and dynamic range necessary for discriminating key
      subcellular structures, such as small axonal, dendritic and glial processes,
      synapses, smooth endoplasmic reticulum, vesicles, microtubules, polyribosomes,
      and endosomes which are critical for neuronal function. Individual image fields
      from the tSEM system were up to 4,295 um(2) (65.54 um per side) at 2 nm pixel
      size, contrasting with image fields from a modern transmission electron
      microscope (TEM) system, which were only 66.59 um(2) (8.160 um per side) at the
      same pixel size. The tSEM produced outstanding images and had reduced distortion
      and drift relative to TEM. Automated stage and scan control in tSEM easily
      provided unattended serial section imaging and montaging. Lens and scan
      properties on both TEM and SEM platforms revealed no significant nonlinear
      distortions within a central field of ~100 um(2) and produced near-perfect image
      registration across serial sections using the computational elastic alignment
      tool in Fiji/TrakEM2 software, and reliable geometric measurements from
      RECONSTRUCTTM or Fiji/TrakEM2 software. Axial resolution limits the analysis of
      small structures contained within a section (~45 nm). Since this new tSEM is non
      destructive, objects within a section can be explored at finer axial resolution
      in TEM tomography with current methods. Future development of tSEM tomography
      promises thinner axial resolution producing nearly isotropic voxels and should
      provide within-section analyses of structures without changing platforms. Brain
      was the test system given our interest in synaptic connectivity and plasticity;
      however, the new tSEM system is readily applicable to other biological systems.

PMID- 23555710
TI  - Preferential binding of hot spot mutant p53 proteins to supercoiled DNA in vitro
      and in cells.
AB  - Hot spot mutant p53 (mutp53) proteins exert oncogenic gain-of-function
      activities. Binding of mutp53 to DNA is assumed to be involved in mutp53-mediated
      repression or activation of several mutp53 target genes. To investigate the
      importance of DNA topology on mutp53-DNA recognition in vitro and in cells, we
      analyzed the interaction of seven hot spot mutp53 proteins with topologically
      different DNA substrates (supercoiled, linear and relaxed) containing and/or
      lacking mutp53 binding sites (mutp53BS) using a variety of electrophoresis and
      immunoprecipitation based techniques. All seven hot spot mutp53 proteins (R175H,
      G245S, R248W, R249S, R273C, R273H and R282W) were found to have retained the
      ability of wild-type p53 to preferentially bind circular DNA at native negative
      superhelix density, while linear or relaxed circular DNA was a poor substrate.
      The preference of mutp53 proteins for supercoiled DNA (supercoil-selective
      binding) was further substantiated by competition experiments with linear DNA or
      relaxed DNA in vitro and ex vivo. Using chromatin immunoprecipitation, the
      preferential binding of mutp53 to a sc mutp53BS was detected also in cells.
      Furthermore, we have shown by luciferase reporter assay that the DNA topology
      influences p53 regulation of BAX and MSP/MST1 promoters. Possible modes of mutp53
      binding to topologically constrained DNA substrates and their biological
      consequences are discussed.

PMID- 23555713
TI  - A series of TA-based and zero-background vectors for plant functional genomics.
AB  - With the sequencing of genomes from many organisms now complete and the
      development of high-throughput sequencing, life science research has entered the
      functional post-genome era. Therefore, deciphering the function of genes and how
      they interact is in greater demand. To study an unknown gene, the basic methods
      are either overexpression or gene knockout by creating transgenic plants, and
      gene construction is usually the first step. Although traditional cloning
      techniques using restriction enzymes or a site-specific recombination system
      (Gateway or Clontech cloning technology) are highly useful for efficiently
      transferring DNA fragments into destination plasmids, the process is time
      consuming and expensive. To facilitate the procedure of gene construction, we
      designed a TA-based cloning system in which only one step was needed to subclone
      a DNA fragment into vectors. Such a cloning system was developed from the pGreen
      binary vector, which has a minimal size and facilitates construction
      manipulation, combined with the negative selection marker gene ccdB, which has
      the advantages of eliminating the self-ligation background and directly enabling
      high-efficiency TA cloning technology. We previously developed a set of transient
      and stable transformation vectors for constitutive gene expression, gene
      silencing, protein tagging, subcellular localization analysis and promoter
      activity detection. Our results show that such a system is highly efficient and
      serves as a high-throughput platform for transient or stable transformation in
      plants for functional genome research.

PMID- 23555712
TI  - Role of a novel functional variant in the PPP2R1A promoter on the regulation of
      PP2A-Aalpha and the risk of hepatocellular carcinoma.
AB  - Previously, we identified the genetic variant -241 (-/G) (rs11453459) in the PP2A
      Aalpha gene (PPP2R1A) promoter and demonstrated that this variant influences the
      DNA-binding affinity of nuclear factor-kappa B (NF-kappaB). In this study, we
      further confirmed that the transcriptional activity of PPP2R1A may be regulated
      by NF-kappaB through the functional genetic variant -241 (-/G). Moreover, we also
      demonstrated that the methylation status of CpG islands in the promoter of
      PPP2R1A influences the activity of this gene promoter. Few studies have examined
      the role of this -241 (-/G) variant in genetic or epigenetic regulation in
      hepatocellular carcinoma (HCC). To investigate whether this functional variant in
      the PPP2R1A promoter is associated with the risk of HCC and confirm the function
      of the -241 (-/G) variant in the HCC population, we conducted a case-control
      study involving 251 HCC cases and 252 cancer-free controls from a Han population
      in southern China. Compared with the -241 (--) homozygote, the heterozygous -241
      (-G) genotype (adjusted OR  = 0.32, 95% confidence interval (CI)  = 0.17-0.58,
      P<0.001) and the -241 (-G)/(GG) genotypes (adjusted OR  = 0.38, 95% CI  = 0.22
      0.67, P  = 0.001) were both significantly associated with a reduced risk of HCC.
      Stratification analysis indicated that the protective role of -241 (-G) was more
      pronounced in individuals who were <= 40 years of age, female and HBV-negative.
      Our data suggest that the transcriptional activity of PPP2R1A is regulated by NF
      kappaB through the -241 (-/G) variant and by the methylation of the promoter
      region. Moreover, the functional -241 (-/G) variant in the PPP2R1A promoter
      contributes to the decreased risk of HCC. These findings contribute novel
      information regarding the gene transcription of PPP2R1A regulated by the
      polymorphism and methylation in the promoter region through genetic and
      epigenetic mechanisms in hepatocarcinogenesis.

PMID- 23555714
TI  - The internal architecture of leukocyte lipid body organelles captured by three
      dimensional electron microscopy tomography.
AB  - Lipid bodies (LBs), also known as lipid droplets, are complex organelles of all
      eukaryotic cells linked to a variety of biological functions as well as to the
      development of human diseases. In cells from the immune system, such as
      eosinophils, neutrophils and macrophages, LBs are rapidly formed in the cytoplasm
      in response to inflammatory and infectious diseases and are sites of synthesis of
      eicosanoid lipid mediators. However, little is known about the structural
      organization of these organelles. It is unclear whether leukocyte LBs contain a
      hydrophobic core of neutral lipids as found in lipid droplets from adipocytes and
      how diverse proteins, including enzymes involved in eicosanoid formation,
      incorporate into LBs. Here, leukocyte LB ultrastructure was studied in detail by
      conventional transmission electron microscopy (TEM), immunogold EM and electron
      tomography. By careful analysis of the two-dimensional ultrastructure of LBs from
      human blood eosinophils under different conditions, we identified membranous
      structures within LBs in both resting and activated cells. Cyclooxygenase, a
      membrane inserted protein that catalyzes the first step in prostaglandin
      synthesis, was localized throughout the internum of LBs. We used fully automated
      dual-axis electron tomography to study the three-dimensional architecture of LBs
      in high resolution. By tracking 4 nm-thick serial digital sections we found that
      leukocyte LBs enclose an intricate system of membranes within their "cores".
      After computational reconstruction, we showed that these membranes are organized
      as a network of tubules which resemble the endoplasmic reticulum (ER). Our
      findings explain how membrane-bound proteins interact and are spatially arranged
      within LB "cores" and support a model for LB formation by incorporating
      cytoplasmic membranes of the ER, instead of the conventional view that LBs emerge
      from the ER leaflets. This is important to understand the functional capabilities
      of leukocyte LBs in health and during diverse diseases in which these organelles
      are functionally involved.

PMID- 23555715
TI  - Automated objective routine examination of optical quality of rigid endoscopes in
      a clinical setting.
AB  - Rigid endoscopes degrade during clinical use due to sterilization, ionizing
      radiation and mechanical forces. Despite visual checks on functionality at the
      department of sterilization, surgeons are still confronted with suboptimal
      instruments as it is difficult to assess this degradation in an objective manner.
      To guarantee that endoscopes have sufficient optical quality for minimal invasive
      surgery, an experimental opto-electronic test bench has been developed in order
      to be used at the department of sterilization. Transmission of illumination
      fibres and lens contrast values are stored in a database to enable empirical
      criteria to reject endoscope for further clinical usage or to accept endoscopes
      after repair. Results of the test bench are given for an eight month period,
      where a trained operator performed 1599 measurements on 46 different types.
      Stability of the system, trends in quality of clinical endoscopes, and effect of
      repair or replacement were assessed. Although the period was too short to draw
      firm conclusions, a slow downwards trend in quality of clinically used endoscopes
      could be observed. Also, endoscopes generally improve in quality after repair or
      replacement, while endoscope replacement seems to slightly outperform endoscope
      repair. To optimize the measurement process, a new system is being developed
      requiring less user interaction and measuring more optical parameters of an
      endoscope. By commercializing this system, we hope that measurements at different
      hospitals will give improved insight which acceptance and rejection criteria to
      use and which factors (usage, cleaning protocol, and brands) determine the
      economic lifetime of endoscopes.

PMID- 23555716
TI  - Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction
      training.
AB  - Fear behavior is vital for survival and involves learning contingent associations
      of non-threatening cues with aversive stimuli. In contrast, excessive levels of
      fear can be maladaptive and lead to anxiety disorders. Generally, extensive
      sessions of extinction training correlates with reduced spontaneous recovery. The
      molecular mechanisms underlying the long-term inhibition of fear recovery
      following repeated extinction training are not fully understood. Here we show
      that in rats, prolonged extinction training causes greater reduction in both fear
      potentiated startle and spontaneous recovery. This effect was specifically
      blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1
      antagonists and by a protein synthesis inhibitor. Similar inhibition of memory
      recovery following prolonged extinction training was also observed in mice. In
      agreement with the instrumental role of mGluR5 in the prolonged inhibition of
      fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated
      signaling exhibit lower spontaneous recovery of fear after extinction training
      than wild-type littermates. At the molecular level, we discovered that prolonged
      extinction training reversed the fear conditioning-induced increase in surface
      expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and
      synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a
      synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged
      extinction training-induced inhibition of fear recovery. Together, our results
      demonstrate that prolonged extinction training results in the mGluR5-dependent
      long-term inhibition of fear recovery. This effect may involve the degradation of
      original memory and may explain the beneficial effects of prolonged exposure
      therapy for the treatment of phobias.

PMID- 23555717
TI  - Pre-S deletion and complex mutations of hepatitis B virus related to young age
      hepatocellular carcinoma in Qidong, China.
AB  - BACKGROUND/AIM: To investigate the roles of biomedical factors, hepatitis B virus
      (HBV) DNA levels, genotypes, and specific viral mutation patterns on the
      progression of hepatocellular carcinoma (HCC) patients below 40 years of age in
      Qidong, China. METHODS: We conducted a case-control study within a cohort of 2387
      male HBV carriers who were recruited from August, 1996. The HBV DNA sequence was
      determined in 49 HCC and 90 chronic hepatitis (CH) patients below 40 years of
      age. Mutation exchanges during follow-up in 32 cases were compared with 65
      controls with paired serum samples. In addition, a consecutive series of samples
      from 14 HCC cases were employed to compare the sequences before and after the
      occurrence of HCC. RESULTS: After adjustment for age, history of cigarette
      smoking and alcohol consumption, HBeAg positive, HBV DNA levels >=4.00 log(10)
      copies/mL, pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768
      mutations were associated with risk of young age HCC. Moreover, the presence of
      an increasing number of HCC-related mutations (pre-S deletion, T1762/A1764, and
      T1766 and/or A1768 mutations) was associated with an increased risk of young age
      HCC. Paired samples analysis indicated that the increased HCC risk for at-risk
      sequence mutations were attributable to the persistence of these mutations, but
      not a single time point mutation. The longitudinal observation demonstrated a
      gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766
      and/or A1768 mutations during the development of HCC. CONCLUSION: High HBV DNA
      levels and pre-S deletion were independent risk factors of young age HCC.
      Combination of pre-S deletion and core promoter mutations increased the risk and
      persistence of at-risk sequence mutations is critical for HCC development.

PMID- 23555718
TI  - Ubiquitin-like protein from human placental extract exhibits collagenase
      activity.
AB  - An aqueous extract of human placenta exhibits strong gelatinase/collagenase
      activity in zymography. 2-D gel electrophoresis of the extract with gelatin
      zymography in the second dimension displayed a single spot, identified as
      ubiquitin-like component upon MALDI/TOF MS/MS analysis. Immunoblot indicated
      presence of ubiquitin and absence of collagenase in the extract. Collagenase
      activity of the ubiquitin-like component was confirmed from the change in
      solubility of collagen in aqueous buffer, degradation of collagen by size
      exclusion HPLC and atomic force microscopy. Quantification with DQ-gelatin showed
      that the extract contains 0.04 U/ml of collagenase activity that was inhibited up
      to 95% by ubiquitin antibody. Ubiquitin from bovine erythrocytes demonstrated
      mild collagenase activity. Bioinformatics studies suggest that placental
      ubiquitin and collagenase follow structurally divergent evolution. This
      thermostable intrinsic collagenase activity of placental extract might have wide
      physiological relevance in degrading and remodeling collagen as it is used as a
      drug for wound healing and pelvic inflammatory diseases.

PMID- 23555719
TI  - HCMV activates the IL-6-JAK-STAT3 axis in HepG2 cells and primary human
      hepatocytes.
AB  - OBJECTIVES: There has been increased interest in the possible role of human
      cytomegalovirus (HCMV) in carcinogenesis during the last decade. HCMV
      seroprevalence was enhanced in patients with hepatocellular carcinoma (HCC) but a
      possible relationship between HCC and HCMV infection remained to be assessed. The
      aim of this work was to investigate the pro-tumor influence of HCMV on primary
      human hepatocytes (PHH) and HepG2 cells. METHODS: Following infection of PHH and
      HepG2 cells by two different strains of HCMV, we measured the production of IL-6
      in culture supernatants by ELISA and the protein levels of STAT3, pSTAT3, JAK,
      cyclin D1, survivin, p53, p21, and Mdm2 by western Blotting in infected and
      uninfected cells. Cell proliferation and transformation were investigated using
      Ki67Ag expression measurement and soft-agar colony formation assay respectively.
      RESULTS: Infection of HepG2 cells and PHH by HCMV resulted in the production of
      IL-6 and the subsequent activation of the IL-6R-JAK-STAT3 pathway. HCMV increased
      the expression of cyclin D1 and survivin. Cell proliferation was enhanced in
      HepG2 and PHH infected with HCMV, despite a paradoxical overexpression of p53 and
      p21. More importantly, we observed the formation of colonies in soft agar seeded
      with PHH infected with HCMV and when we challenged the HepG2 cultures to form
      tumorspheres, we found that the HCMV-infected cultures formed 2.5-fold more
      tumorspheres than uninfected cultures. CONCLUSION: HCMV activated the IL-6-JAK
      STAT3 pathway in PHH and HepG2 cells, favored cellular proliferation, induced PHH
      transformation and enhanced HepG2 tumorsphere formation. Our observations raise
      the possibility that HCMV infection might be involved in the genesis of
      hepatocellular carcinoma.

PMID- 23555720
TI  - Single residues in the outer pore of TRPV1 and TRPV3 have temperature-dependent
      conformations.
AB  - Thermosensation is mediated by ion channels that are highly temperature
      sensitive. Several members of the family of transient receptor potential (TRP)
      ion channels are activated by cold or hot temperatures and have been shown to
      function as temperature sensors in vivo. The molecular mechanism of temperature
      sensitivity of these ion channels is not understood. A number of domains or even
      single amino acids that regulate temperature-sensitivity have been identified in
      several TRP channels. However, it is unclear what precise conformational changes
      occur upon temperature activation. Here, we used the cysteine accessibility
      method to probe temperature-dependent conformations of single amino acids in TRP
      channels. We screened over 50 amino acids in the predicted outer pore domains of
      the heat-activated ion channels TRPV1 and TRPV3. In both ion channels we found
      residues that have temperature-dependent accessibilities to the extracellular
      solvent. The identified residues are located within the second predicted
      extracellular pore loop. These residues are identical or proximal to residues
      that were shown to be specifically required for temperature-activation, but not
      chemical activation. Our data precisely locate conformational changes upon
      temperature-activation within the outer pore domain. Collectively, this suggests
      that these specific residues and the second predicted pore loop in general are
      crucial for the temperature-activation mechanism of these heat-activated
      thermoTRPs.

PMID- 23555721
TI  - Multiple symbiont acquisition strategies as an adaptive mechanism in the coral
      Stylophora pistillata.
AB  - In obligate symbioses, the host's survival relies on the successful acquisition
      and maintenance of symbionts. Symbionts can either be transferred from parent to
      offspring via direct inheritance (vertical transmission) or acquired anew each
      generation from the environment (horizontal transmission). With vertical symbiont
      transmission, progeny benefit by not having to search for their obligate
      symbionts, and, with symbiont inheritance, a mechanism exists for perpetuating
      advantageous symbionts. But, if the progeny encounter an environment that differs
      from that of their parent, they may be disadvantaged if the inherited symbionts
      prove suboptimal. Conversely, while in horizontal symbiont acquisition host
      survival hinges on an unpredictable symbiont source, an individual host may
      acquire genetically diverse symbionts well suited to any given environment. In
      horizontal acquisition, however, a potentially advantageous symbiont will not be
      transmitted to subsequent generations. Adaptation in obligate symbioses may
      require mechanisms for both novel symbiont acquisition and symbiont inheritance.
      Using denaturing-gradient gel electrophoresis and real-time PCR, we identified
      the dinoflagellate symbionts (genus Symbiodinium) hosted by the Red Sea coral
      Stylophora pistillata throughout its ontogenesis and over depth. We present
      evidence that S. pistillata juvenile colonies may utilize both vertical and
      horizontal symbiont acquisition strategies. By releasing progeny with maternally
      derived symbionts, that are also capable of subsequent horizontal symbiont
      acquisition, coral colonies may acquire physiologically advantageous novel
      symbionts that are then perpetuated via vertical transmission to subsequent
      generations. With symbiont inheritance, natural selection can act upon the
      symbiotic variability, providing a mechanism for coral adaptation.

PMID- 23555722
TI  - Cytotoxic effects of curcumin in human retinal pigment epithelial cells.
AB  - BACKGROUND: Curcumin from turmeric is an ingredient in curry powders. Due to its
      antiinflammatory, antioxidant and anticarcinogenic effects, curcumin is a
      promising drug for the treatment of cancer and retinal diseases. We investigated
      whether curcumin alters the viability and physiological properties of human
      retinal pigment epithelial (RPE) cells in vitro. METHODOLOGY/PRINCIPAL FINDINGS:
      Cellular proliferation was investigated with a bromodeoxy-uridine immunoassay,
      and chemotaxis was investigated with a Boyden chamber assay. Cell viability was
      determined by trypan blue exclusion. Apoptosis and necrosis rates were determined
      with a DNA fragmentation ELISA. Gene expression was determined by real-time PCR,
      and secretion of VEGF and bFGF was examined with ELISA. The phosphorylation level
      of proteins was revealed by Western blotting. The proliferation of RPE cells was
      slightly increased by curcumin at 10 uM and strongly reduced by curcumin above 50
      uM. Curcumin at 50 uM increased slightly the chemotaxis of the cells. Curcumin
      reduced the expression and secretion of VEGF under control conditions and
      abolished the VEGF secretion induced by PDGF and chemical hypoxia. Whereas low
      concentrations of curcumin stimulated the expression of bFGF and HGF, high
      concentrations caused downregulation of both factors. Curcumin decreased dose
      dependently the viability of RPE cells via induction of early necrosis (above 10
      uM) and delayed apoptosis (above 1 uM). The cytotoxic effect of curcumin involved
      activation of caspase-3 and calpain, intracellular calcium signaling,
      mitochondrial permeability, oxidative stress, increased phosphorylation of p38
      MAPK and decreased phosphorylation of Akt protein. CONCLUSION: It is concluded
      that curcumin at concentrations described to be effective in the treatment of
      tumor cells and in inhibiting death of retinal neurons (~10 uM) has adverse
      effects on RPE cells. It is suggested that, during the intake of curcumin as
      concomitant therapy of cancer or in the treatment of eye diseases, retinal
      function should be monitored carefully.

PMID- 23555723
TI  - Abnormal apoptosis of trophoblastic cells is related to the up-regulation of
      CYP11A gene in placenta of preeclampsia patients.
AB  - Abnormal placenta trophoblast proliferation and apoptosis is related to the
      pathogenesis of preeclampsia. Emerging evidence has also indicated that key
      pregnancy-associated hormones, such as hCG, progesterone, are found in high
      concentration at the maternal-fetal interface. The purpose of this study was to
      investigate the expression of CYP11A, a key enzyme in steroid hormone synthesis
      and metabolism, in normal pregnancy and severe preeclampsia placenta and to
      explore the underlying mechanism of the relationship between the altered CYP11A
      expression and onset of preeclampsia. Immunohistochemistry method was used to
      study the localization of CYP11A-encoded protein P450scc in the placenta; reverse
      transcription polymerase chain reaction (RT-PCR) and Western blotting were used
      to examine CYP11A expression at mRNA and protein levels in patients with severe
      preeclampsia and normal placental tissue. CYP11A overexpression in trophoblastic
      cells was used to evaluate the effect on viability. TUNEL staining was used to
      determine whether overexpression of CYP11A could affect trophoblastic cell
      apoptosis. The results showed that CYP11A was selectively expressed in the
      cytoplasm of the placental trophoblastic cells. CYP11A expression were
      significantly increased in severe preeclampsia compared with normal pregnancy in
      both mRNA and protein levels. Multiple regression analysis indicated that CYP11A
      gene expression was positively correlated to ALT level and Plt, while negatively
      correlated to INR. Overexpression of CYP11A reduced trophoblastic cell
      proliferation and induced HTR8/SVneo cells apoptosis through activation of
      activated caspase-3 expression. These results suggest that abnormally high
      expression of CYP11A inhibits trophoblastic proliferation and increases apoptosis
      and therefore could be involved in the pathogenesis of preeclampsia.

PMID- 23555724
TI  - Oxidative stress induces monocyte necrosis with enrichment of cell-bound albumin
      and overexpression of endoplasmic reticulum and mitochondrial chaperones.
AB  - In the present study, monocytes were treated with 5-azacytidine (azacytidine),
      gossypol or hydrogen peroxide to induce cell death through oxidative stress. A
      shift from apoptotic to necrotic cell death occurred when monocytes were treated
      with 100 uM azacytidine for more than 12 hours. Necrotic monocytes exhibited
      characteristics, including enrichment of cell-bound albumin and up-regulation of
      endoplasmic reticulum (ER)- and mitochondrial-specific chaperones to protect
      mitochondrial integrity, which were not observed in other necrotic cells,
      including HUH-7, A2780, A549 and HOC1a. Our results show that the cell-bound
      albumin originates in the culture medium rather than from monocyte-derived
      hepatocytes, and that HSP60 is a potential binding partner of the cell-bound
      albumin. Proteomic analysis shows that HSP60 and protein disulfide isomerase are
      the most abundant up-regulated mitochondrial and ER-chaperones, and that both
      HSP60 and calreticulin are ubiquitinated in necrotic monocytes. In contrast,
      expression levels of the cytosolic chaperones HSP90 and HSP71 were down-regulated
      in the azacytidine-treated monocytes, concomitant with an increase in the levels
      of these chaperones in the cell culture medium. Collectively, our results
      demonstrates that chaperones from different organelles behave differently in
      necrotic monocytes, ER- and mitochondrial chaperones being retained and cytosolic
      and nuclear chaperones being released into the cell culture medium through the
      ruptured cell membrane. HSP60 may serve as a new target for development of
      myeloid leukemia treatment.

PMID- 23555725
TI  - Targeted induction of interferon-lambda in humanized chimeric mouse liver
      abrogates hepatotropic virus infection.
AB  - BACKGROUND & AIMS: The interferon (IFN) system plays a critical role in innate
      antiviral response. We presume that targeted induction of IFN in human liver
      shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus
      (HBV). METHODS: This study used chimeric mice harboring humanized livers and
      infected with HCV or HBV. This mouse model permitted simultaneous analysis of
      immune responses by human and mouse hepatocytes in the same liver and exploration
      of the mechanism of antiviral effect against these viruses. Targeted expression
      of IFN was induced by treating the animals with a complex comprising a
      hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC
      (LIC-pIC). Viral replication, IFN gene expression, IFN protein production, and
      IFN antiviral activity were analyzed (for type I, II and III IFNs) in the livers
      and sera of these humanized chimeric mice. RESULTS: Following treatment with LIC
      pIC, the humanized livers of chimeric mice exhibited increased expression (at the
      mRNA and protein level) of human IFN-lambdas, resulting in strong antiviral
      effect on HBV and HCV. Similar increases were not seen for human IFN-alpha or IFN
      beta in these animals. Strong induction of IFN-lambdas by LIC-pIC occurred only
      in human hepatocytes, and not in mouse hepatocytes nor in human cell lines
      derived from other (non-hepatic) tissues. LIC-pIC-induced IFN-lambda production
      was mediated by the immune sensor adaptor molecules mitochondrial antiviral
      signaling protein (MAVS) and Toll/IL-1R domain-containing adaptor molecule-1
      (TICAM-1), suggesting dual recognition of LIC-pIC by both sensor adaptor
      pathways. CONCLUSIONS: These findings demonstrate that the expression and
      function of various IFNs differ depending on the animal species and tissues under
      investigation. Chimeric mice harboring humanized livers demonstrate that IFN
      lambdas play an important role in the defense against human hepatic virus
      infection.

PMID- 23555726
TI  - A molecular phylogeny of Plesiorycteropus reassigns the extinct mammalian order
      'Bibymalagasia'.
AB  - Madagascar is well known for its diverse fauna and flora, being home to many
      species not found anywhere else in the world. However, its biodiversity in the
      recent past included a range of extinct enigmatic fauna, such as elephant birds,
      giant lemurs and dwarfed hippopotami. The 'Malagasy aardvark' (Plesiorycteropus)
      has remained one of Madagascar's least well-understood extinct species since its
      discovery in the 19(th) century. Initially considered a close relative of the
      aardvark (Orycteropus) within the order Tubulidentata, more recent morphological
      analyses challenged this placement on the grounds that the identifiably derived
      traits supporting this allocation were adaptations to digging rather than shared
      ancestry. Because the skeletal evidence showed many morphological traits
      diagnostic of different eutherian mammal orders, they could not be used to
      resolve its closest relatives. As a result, the genus was tentatively assigned
      its own taxonomic order 'Bibymalagasia', yet how this order relates to other
      eutherian mammal orders remains unclear despite numerous morphological
      investigations. This research presents the first known molecular sequence data
      for Plesiorycteropus, obtained from the bone protein collagen (I), which places
      the 'Malagasy aardvark' as more closely related to tenrecs than aardvarks. More
      specifically, Plesiorycteropus was recovered within the order Tenrecoidea (golden
      moles and tenrecs) within Afrotheria, suggesting that the taxonomic order
      'Bibymalagasia' is obsolete. This research highlights the potential for collagen
      sequencing in investigating the phylogeny of extinct species as a viable
      alternative to ancient DNA (aDNA) sequencing, particularly in cases where aDNA
      cannot be recovered.

PMID- 23555727
TI  - Ultra performance liquid chromatography-based metabonomic study of therapeutic
      effect of the surface layer of Poria cocos on adenine-induced chronic kidney
      disease provides new insight into anti-fibrosis mechanism.
AB  - The surface layer of Poria cocos (Fu-Ling-Pi, FLP) is commonly used in
      traditional Chinese medicine and its diuretic effect was confirmed in rat. Ultra
      performance liquid chromatography/quadrupole time-of-flight high-sensitivity mass
      spectrometry and a novel mass spectrometry(Elevated Energy) data collection
      technique was employed to investigate metabonomic characteristics of chronic
      kidney disease (CKD) induced from adenine excess and the protective effects of
      FLP. Multiple metabolites are detected in the CKD and are correlated with
      progressive renal injury. Among these biomarkers, lysoPC(18?0),
      tetracosahexaenoic acid, lysoPC(18?2), creatinine, lysoPC (16?0) and
      lysoPE(22?0/0?0) in the FLP-treated group were completely reversed to levels in
      the control group which lacked CKD. Combined with biochemistry and histopathology
      results, the changes in serum metabolites indicate that the perturbations of
      phospholipids metabolism, energy metabolism and amino acid metabolism are related
      to adenine-induced CKD and to the interventions of FLP on all the three metabolic
      pathways. FLP may regulate the metabolism of these biomarkers, especially their
      efficient utilization within the context of CKD. Furthermore, these biomarkers
      might serve as characteristics to explain the mechanisms of FLP.

PMID- 23555729
TI  - Etiology and audiological outcomes at 3 years for 364 children in Australia.
AB  - Hearing loss is an etiologically heterogeneous trait with differences in the age
      of onset, severity and site of lesion. It is caused by a combination of genetic
      and/or environmental factors. A longitudinal study to examine the efficacy of
      early intervention for improving child outcomes is ongoing in Australia. To
      determine the cause of hearing loss in these children we undertook molecular
      testing of perinatal "Guthrie" blood spots of children whose hearing loss was
      either detected via newborn hearing screening or detected later in infancy. We
      analyzed the GJB2 and SLC26A4 genes for the presence of mutations, screened for
      the mitochondrial DNA (mtDNA) A1555G mutation, and screened for congenital CMV
      infection in DNA isolated from dried newborn blood spots. Results were obtained
      from 364 children. We established etiology for 60% of children. One or two known
      GJB2 mutations were present in 82 children. Twenty-four children had one or two
      known SLC26A4 mutations. GJB2 or SLC26A4 changes with unknown consequences on
      hearing were found in 32 children. The A1555G mutation was found in one child,
      and CMV infection was detected in 28 children. Auditory neuropathy spectrum
      disorder was confirmed in 26 children whose DNA evaluations were negative. A
      secondary objective was to investigate the relationship between etiology and
      audiological outcomes over the first 3 years of life. Regression analysis was
      used to investigate the relationship between hearing levels and etiology. Data
      analysis does not support the existence of differential effects of etiology on
      degree of hearing loss or on progressiveness of hearing loss.

PMID- 23555728
TI  - wFlu: characterization and evaluation of a native Wolbachia from the mosquito
      Aedes fluviatilis as a potential vector control agent.
AB  - There is currently considerable interest and practical progress in using the
      endosymbiotic bacteria Wolbachia as a vector control agent for human vector-borne
      diseases. Such vector control strategies may require the introduction of
      multiple, different Wolbachia strains into target vector populations,
      necessitating the identification and characterization of appropriate endosymbiont
      variants. Here, we report preliminary characterization of wFlu, a native
      Wolbachia from the neotropical mosquito Aedes fluviatilis, and evaluate its
      potential as a vector control agent by confirming its ability to cause
      cytoplasmic incompatibility, and measuring its effect on three parameters
      determining host fitness (survival, fecundity and fertility), as well as vector
      competence (susceptibility) for pathogen infection. Using an aposymbiotic strain
      of Ae. fluviatilis cured of its native Wolbachia by antibiotic treatment, we show
      that in its natural host wFlu causes incomplete, but high levels of,
      unidirectional cytoplasmic incompatibility, has high rates of maternal
      transmission, and no detectable fitness costs, indicating a high capacity to
      rapidly spread through host populations. However, wFlu does not inhibit, and even
      enhances, oocyst infection with the avian malaria parasite Plasmodium
      gallinaceum. The stage- and sex-specific density of wFlu was relatively low, and
      with limited tissue distribution, consistent with the lack of virulence and
      pathogen interference/symbiont-mediated protection observed. Unexpectedly, the
      density of wFlu was also shown to be specifically-reduced in the ovaries after
      bloodfeeding Ae. fluviatilis. Overall, our observations indicate that the
      Wolbachia strain wFlu has the potential to be used as a vector control agent, and
      suggests that appreciable mutualistic coevolution has occurred between this
      endosymbiont and its natural host. Future work will be needed to determine
      whether wFlu has virulent host effects and/or exhibits pathogen interference when
      artificially-transfected to the novel mosquito hosts that are the vectors of
      human pathogens.

PMID- 23555730
TI  - Intracranial injection of AAV expressing NEP but not IDE reduces amyloid
      pathology in APP+PS1 transgenic mice.
AB  - The accumulation of beta-amyloid peptides in the brain has been recognized as an
      essential factor in Alzheimer's disease pathology. Several proteases, including
      Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading
      enzyme (IDE), have been shown to cleave beta-amyloid peptides (Abeta). We have
      previously reported reductions in amyloid in APP+PS1 mice with increased
      expression of ECE. In this study we compared the vector-induced increased
      expression of NEP and IDE. We used recombinant adeno-associated viral vectors
      expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered
      secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study,
      immunohistochemistry staining for total Abeta was significantly decreased in
      animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the
      hippocampus or cortex. Congo red staining followed a similar trend revealing
      significant decreases in the hippocampus and the cortex for NEP-n and NEP-s
      treatment groups. Our results indicate that while rAAV-IDE does not have the same
      therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing
      amyloid loads, and both of these vectors continue to have significant effects
      nine months post-injection. As such, they may be considered reasonable candidates
      for gene therapy trials in AD.

PMID- 23555731
TI  - Global conformational selection and local induced fit for the recognition between
      intrinsic disordered p53 and CBP.
AB  - The transactivation domain (TAD) of tumor suppressor p53 can bind with the
      nuclear coactivator binding domain (NCBD) of cyclic-AMP response element binding
      protein (CBP) and activate transcription. NMR experiments demonstrate that both
      apo-NCBD and TAD are intrinsic disordered and bound NCBD/TAD undergoes a
      transition to well folded. The recognition mechanism between intrinsic disordered
      proteins is still hotly debated. Molecular dynamics (MD) simulations in explicit
      solvent are used to study the recognition mechanism between intrinsic disordered
      TAD and NCBD. The average RMSD values between bound and corresponding apo states
      and Kolmogorov-Smirnov P test analysis indicate that TAD and NCBD may follow an
      induced fit mechanism. Quantitative analysis indicates there is also a global
      conformational selection. In summary, the recognition of TAD and NCBD might obey
      a local induced fit and global conformational selection. These conclusions are
      further supported by high-temperature unbinding kinetics and room temperature
      landscape analysis. These methods can be used to study the recognition mechanism
      of other intrinsic disordered proteins.

PMID- 23555732
TI  - Association between CASR polymorphisms, calcium intake, and colorectal cancer
      risk.
AB  - AIM: The current study aimed to assess the effect of dietary calcium intake and
      possible interactions with calcium-sensing receptor (CASR) gene polymorphisms on
      colorectal cancer risk. METHODS: A total of 420 colorectal cancer cases and 815
      controls were included in the analysis. Calcium intake was investigated using a
      103 item semi-quantitative food frequency questionnaire, and four single
      nucleotide polymorphisms (SNPs) within the CASR, rs10934578, rs12485716,
      rs2270916, and rs4678174, were evaluated. RESULTS: No SNPs were associated with
      colorectal cancer risk after adjusting for covariates. Overall, no significant
      effect modification by CASR polymorphisms on the association between calcium
      intake and colorectal cancer risk were detected. However, all 4 of the
      polymorphisms within the CASR showed significantly higher odds ratios for
      association with colorectal cancer risk in the low-calcium-intake group compared
      to the high-calcium-intake group. In the case of rs2270916, individuals with the
      CC genotype and low calcium intake showed an increased colorectal cancer risk
      compared to their counterparts with the TT genotype and high calcium intake (OR =
      2.11, 95% CI = 1.27-3.51). CONCLUSIONS: Subjects with lower calcium intake
      exhibited a higher colorectal cancer risk compared with subjects with the same
      genotype who had higher calcium intake. Our results suggest that individuals who
      have low dietary calcium intake should be aware of their increased colorectal
      cancer risk and prevention strategies.

PMID- 23555733
TI  - Weight-loss induced changes in physical activity and activity energy expenditure
      in overweight and obese subjects before and after energy restriction.
AB  - Activity energy expenditure (AEE) is the component of daily energy expenditure
      that is mainly influenced by the amount of physical activity (PA) and by the
      weight of the body displaced. This study aimed at analyzing the effect of weight
      loss on PA and AEE. The body weight and PA of 66 overweight and obese subjects
      were measured at baseline and after 12 weeks of 67% energy restriction. PA was
      measured using a tri-axial accelerometer for movement registration (Tracmor) and
      quantified in activity counts. Tracmor recordings were also processed using a
      classification algorithm to recognize 6 common activity types engaged in during
      the day. A doubly-labeled water validated equation based on Tracmor output was
      used to estimate AEE. After weight loss, body weight decreased by 13+/-4%, daily
      activity counts augmented by 9% (95% CI: +2%, +15%), and this increase was weakly
      associated with the decrease in body weight (R(2) = 7%; P<0.05). After weight
      loss subjects were significantly (P<0.05) less sedentary (-26 min/d), and
      increased the time spent walking (+11 min/d) and bicycling (+4 min/d). However,
      AEE decreased by 0.6+/-0.4 MJ/d after weight loss. On average, a 2-hour/day
      reduction of sedentary time by increasing ambulatory and generic activities was
      required to restore baseline levels of AEE. In conclusion, after weight loss PA
      increased but the related metabolic demand did not offset the reduction in AEE
      due to the lower body weight. Promoting physical activity according to the extent
      of weight loss might increase successfulness of weight maintenance.

PMID- 23555734
TI  - A novel peptide delivers plasmids across blood-brain barrier into neuronal cells
      as a single-component transfer vector.
AB  - There is no data up to now to show that peptide can deliver plasmid into brain as
      a single-component transfer vector. Here we show that a novel peptide, RDP
      (consisted of 39 amino acids), can be exploited as an efficient plasmid vector
      for brain-targeting delivery. The plasmids containing Lac Z reporter gene (pVAX
      Lac Z) and BDNF gene (pVAX-BDNF) are complexed with RDP and intravenously
      injected into mice. The results of gel retardation assay show that RDP enables to
      bind DNA in a dose-dependent manner, and the X-Gal staining identity that Lac Z
      is specifically expressed in the brain. Also, the results of Western blot and
      immunofluorescence staining of BDNF indicate that pVAX-BDNF complexed with RDP
      can be delivered into brain, and show neuroprotective properties in experimental
      Parkinson's disease (PD) model. The results demonstrate that RDP enables to bind
      and deliver DNA into the brain, resulting in specific gene expression in the
      neuronal cells. This strategy provides a novel, simple and effective approach for
      non-viral gene therapy of brain diseases.

PMID- 23555736
TI  - Group independent component analysis and functional MRI examination of changes in
      language areas associated with brain tumors at different locations.
AB  - OBJECT: This study investigates the effect of tumor location on alterations of
      language network by brain tumors at different locations using blood oxygenation
      level dependent (BOLD) fMRI and group independent component analysis (ICA).
      SUBJECTS AND METHODS: BOLD fMRI data were obtained from 43 right handed brain
      tumor patients. Presurgical mapping of language areas was performed on all 43
      patients with a picture naming task. All data were retrospectively analyzed using
      group ICA. Patents were divided into three groups based on tumor locations, i.e.,
      left frontal region, left temporal region or right hemisphere. Laterality index
      (LI) was used to assess language lateralization in each group. RESULTS: The
      results from BOLD fMRI and ICA revealed the different language activation
      patterns in patients with brain tumors located in different brain regions.
      Language areas, such as Broca's and Wernicke's areas, were intact in patients
      with tumors in the right hemisphere. Significant functional changes were observed
      in patients with tumor in the left frontal and temporal areas. More specifically,
      the tumors in the left frontal region affect both Broca's and Wernicke's areas,
      while tumors in the left temporal lobe affect mainly Wernicke's area. The
      compensated activation increase was observed in the right frontal areas in
      patients with left hemisphere tumors. CONCLUSION: Group ICA provides a model free
      alternative approach for mapping functional networks in brain tumor patients.
      Altered language activation by different tumor locations suggested reorganization
      of language functions in brain tumor patients and may help better understanding
      of the language plasticity.

PMID- 23555737
TI  - Edges in agricultural landscapes: species interactions and movement of natural
      enemies.
AB  - Agricultural landscapes can be characterized as a mosaic of habitat patches
      interspersed with hostile matrix, or as a gradient of patches ranging from
      suitable to unsuitable for different species. Arthropods moving through these
      landscapes encounter a range of edges, with different permeability. Patches of
      native vegetation in these landscapes may support natural enemies of crop pests
      by providing alternate hosts for parasitic wasps and/or acting as a source for
      predatory insects. We test this by quantifying species interactions and measuring
      movement across different edge-types. A high diversity of parasitoid species used
      hosts in the native vegetation patches, however we recorded few instances of the
      same parasitoid species using hosts in both the native vegetation and the crop
      (canola). However, we did find overall greater densities of parasitoids moving
      from native vegetation into the crop. Of the parasitoid groups examined,
      parasitoids of aphids (Braconidae: Aphidiinae) frequently moved from native
      vegetation into canola. In contrast, parasitoids of caterpillars (Braconidae:
      Microgastrinae) moved commonly from cereal fields into canola. Late season
      samples showed both aphids and parasitoids moving frequently out of native
      vegetation, in contrast predators moved less commonly from native vegetation
      (across the whole season). The season-long net advantage or disadvantage of
      native vegetation for pest control services is therefore difficult to evaluate.
      It appears that the different edge-types alter movement patterns of natural
      enemies more so than herbivorous pest species, and this may impact pest control
      services.

PMID- 23555735
TI  - Differential immune responses to Segniliparus rotundus and Segniliparus rugosus
      infection and analysis of their comparative virulence profiles.
AB  - Two closely related bacterial species, Segniliparus rotundus and Segniliparus
      rugosus, have emerged as important human pathogens, but little is known about the
      immune responses they elicit or their comparative pathophysiologies. To determine
      the virulence and immune responses of the two species, we compared their
      abilities to grow in phagocytic and non-phagocytic cells. Both species maintained
      non-replicating states within A549 epithelial cells. S. rugosus persisted longer
      and multiplied more rapidly inside murine bone marrow-derived macrophages
      (BMDMs), induced more pro-inflammatory cytokines, and induced higher levels of
      macrophage necrosis. Activation of BMDMs by both species was mediated by toll
      like receptor 2 (TLR2), followed by mitogen-activated protein kinases (MAPK) and
      nuclear factor kappaB (NF-kappaB) signaling pathways, indicating a critical role
      for TLR2 in Segniliparus-induced macrophage activation. S. rugosus triggered
      faster and stronger activation of MAPK signaling and IkappaB degradation,
      indicating that S. rugosus induces more pro-inflammatory cytokines than S.
      rotundus. Multifocal granulomatous inflammations in the liver and lung were
      observed in mice infected with S. rugosus, but S. rotundus was rapidly cleared
      from all organs tested within 15 days post-infection. Furthermore, S. rugosus
      induced faster infiltration of innate immune cells such as neutrophils and
      macrophages to the lung than S. rotundus. Our results suggest that S. rugosus is
      more virulent and induces a stronger immune response than S. rotundus.

PMID- 23555738
TI  - Data acquisition for conservation assessments: is the effort worth it?
AB  - When identifying conservation priorities, the accuracy of conservation
      assessments is constrained by the quality of data available. Despite previous
      efforts exploring how to deal with imperfect datasets, little is known about how
      data uncertainty translates into errors in conservation planning outcomes. Here,
      we evaluate the magnitude of commission and omission error, effectiveness and
      efficiency of conservation planning outcomes derived from three datasets with
      increasing data quality. We demonstrate that investing in data acquisition might
      not always be the best strategy as the magnitude of errors introduced by new
      sites/species can exceed the benefits gained. There was a trade-off between
      effectiveness and efficiency due to poorly sampled rare species. Given that data
      acquisition is limited by the high cost and time required, we recommend focusing
      on improving the quality of data for those species with the highest level of
      uncertainty (rare species) when acquiring new data.

PMID- 23555739
TI  - Campylobacter infection in children in Malawi is common and is frequently
      associated with enteric virus co-infections.
AB  - BACKGROUND: Campylobacter species are the most common cause of bacterial
      gastroenteritis in the developed world. However, comparatively few studies have
      determined the epidemiological features of campylobacteriosis in resource-poor
      settings. METHODS: A total of 1,941 faecal specimens collected from symptomatic
      (diarrhoeic) children and 507 specimens from asymptomatic (non-diarrhoeic)
      children hospitalised in Blantyre, Malawi, between 1997 and 2007, and previously
      tested for the presence of rotavirus and norovirus, was analysed for C. jejuni
      and C. coli using a real time PCR assay. RESULTS: Campylobacter species were
      detected in 415/1,941 (21%) of diarrhoeic children, with C. jejuni accounting for
      85% of all cases. The median age of children with Campylobacter infection was 11
      months (range 0.1-55 months), and was significantly higher than that for children
      with rotavirus and norovirus (6 months and 7 months respectively; P<0.001). Co
      infection with either rotavirus or norovirus was noted in 41% of all cases in the
      diarrhoeic group. In contrast, the detection rate of Campylobacter in the non
      diarrhoeic group was 14%, with viral co-infection identified in 16% of children
      with Campylobacter. There was no association between Campylobacter detection rate
      and season over the 10 year period. DISCUSSION: Using molecular detection
      methodology in hospitalised Malawian children, we have demonstrated a high
      prevalence of Campylobacter infection, with frequent viral co-infection. The
      burden of Campylobacter infection in young African children may be greater than
      previously recognised.

PMID- 23555740
TI  - A multi-paradigm modeling framework to simulate dynamic reciprocity in a
      bioreactor.
AB  - Despite numerous technology advances, bioreactors are still mostly utilized as
      functional black-boxes where trial and error eventually leads to the desirable
      cellular outcome. Investigators have applied various computational approaches to
      understand the impact the internal dynamics of such devices has on overall cell
      growth, but such models cannot provide a comprehensive perspective regarding the
      system dynamics, due to limitations inherent to the underlying approaches. In
      this study, a novel multi-paradigm modeling platform capable of simulating the
      dynamic bidirectional relationship between cells and their microenvironment is
      presented. Designing the modeling platform entailed combining and coupling fully
      an agent-based modeling platform with a transport phenomena computational
      modeling framework. To demonstrate capability, the platform was used to study the
      impact of bioreactor parameters on the overall cell population behavior and vice
      versa. In order to achieve this, virtual bioreactors were constructed and seeded.
      The virtual cells, guided by a set of rules involving the simulated mass
      transport inside the bioreactor, as well as cell-related probabilistic
      parameters, were capable of displaying an array of behaviors such as
      proliferation, migration, chemotaxis and apoptosis. In this way the platform was
      shown to capture not only the impact of bioreactor transport processes on
      cellular behavior but also the influence that cellular activity wields on that
      very same local mass transport, thereby influencing overall cell growth. The
      platform was validated by simulating cellular chemotaxis in a virtual direct
      visualization chamber and comparing the simulation with its experimental
      analogue. The results presented in this paper are in agreement with published
      models of similar flavor. The modeling platform can be used as a concept
      selection tool to optimize bioreactor design specifications.

PMID- 23555741
TI  - Evaluation of in vitro cross-reactivity to avian H5N1 and pandemic H1N1 2009
      influenza following prime boost regimens of seasonal influenza vaccination in
      healthy human subjects: a randomised trial.
AB  - INTRODUCTION: Recent studies have demonstrated that inactivated seasonal
      influenza vaccines (IIV) may elicit production of heterosubtypic antibodies,
      which can neutralize avian H5N1 virus in a small proportion of subjects. We
      hypothesized that prime boost regimens of live and inactivated trivalent seasonal
      influenza vaccines (LAIV and IIV) would enhance production of heterosubtypic
      immunity and provide evidence of cross-protection against other influenza
      viruses. METHODS: In an open-label study, 26 adult volunteers were randomized to
      receive one of four vaccine regimens containing two doses of 2009-10 seasonal
      influenza vaccines administered 8 (+/-1) weeks apart: 2 doses of LAIV; 2 doses of
      IIV; LAIV then IIV; IIV then LAIV. Humoral immunity assays for avian H5N1, 2009
      pandemic H1N1 (pH1N1), and seasonal vaccine strains were performed on blood
      collected pre-vaccine and 2 and 4 weeks later. The percentage of cytokine
      producing T-cells was compared with baseline 14 days after each dose. RESULTS:
      Subjects receiving IIV had prompt serological responses to vaccine strains. Two
      subjects receiving heterologous prime boost regimens had enhanced
      haemagglutination inhibition (HI) and neutralization (NT) titres against pH1N1,
      and one subject against avian H5N1; all three had pre-existing cross-reactive
      antibodies detected at baseline. Significantly elevated titres to H5N1 and pH1N1
      by neuraminidase inhibition (NI) assay were observed following LAIV-IIV
      administration. Both vaccines elicited cross-reactive CD4+ T-cell responses to
      nucleoprotein of avian H5N1 and pH1N1. All regimens were safe and well tolerated.
      CONCLUSION: Neither homologous nor heterologous prime boost immunization enhanced
      serum HI and NT titres to 2009 pH1N1 or avian H5N1 compared to single dose
      vaccine. However heterologous prime-boost vaccination did lead to in vitro
      evidence of cross-reactivity by NI; the significance of this finding is unclear.
      These data support the strategy of administering single dose trivalent seasonal
      influenza vaccine at the outset of an influenza pandemic while a specific vaccine
      is being developed. TRIAL REGISTRATION: ClinicalTrials.gov NCT01044095.

PMID- 23555742
TI  - Occurrence of regulated and emerging iodinated DBPs in the Shanghai drinking
      water.
AB  - Drinking water chlorination plays a pivotal role in preventing pathogen
      contamination against water-borne disease. However, chemical disinfection leads
      to the formation of halogenated disinfection by products (DBPs). Many DBPs are
      highly toxic and are of health concern. In this study, we conducted a
      comprehensive measurements of DBPs, including iodoacetic acid (IAA), iodoform
      (IF), nine haloacetic acids and four trihalomethanes in drinking waters from 13
      water plants in Shanghai, China. The results suggested that IAA and IF were found
      in all the water treatment plants, with maximum levels of 1.66 ug/L and 1.25 ug/L
      for IAA and IF, respectively. Owing to deterioration of water quality, the
      Huangpu River has higher IAA and IF than the Yangtze River. Our results also
      demonstrated that low pH, high natural organic matter, ammonia nitrogen, and
      iodide in source waters increased IAA and IF formation. Compared to chlorine,
      chloramines resulted in higher concentration of iodinated DBP, but reduced the
      levels of trihalomethanes. This is the first study to reveal the widespread
      occurrence of IAA and IF in drinking water in China. The data provide a better
      understanding on the formation of iodinated disinfection byproducts and the
      findings should be useful for treatment process improvement and disinfection
      byproducts controls.

PMID- 23555743
TI  - PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat
      pancreatic beta cells.
AB  - Despite significant progress, the molecular mechanisms responsible for pancreatic
      beta cell depletion and development of diabetes remain poorly defined. At
      present, there is no preventive measure against diabetes. The positive impact of
      CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated
      this study. Our aim was to provide novel insight into the regulation of rat
      CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1
      (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were
      studied by examining their in vitro and in vivo binding affinities for the Cxcl12
      promoter in a pancreatic beta cell line by the electrophoretic mobility shift
      assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and
      YY1 were assessed in transfection experiments using a reporter vector with a
      Cxcl12 promoter sequence driving luciferase gene expression. Experimental
      evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1
      displayed an inhibitory, and YY1 a strong activating effect on Cxcl12
      transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta
      cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to
      the Cxcl12 promoter during basal and in STZ-compromised conditions led us to
      conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early
      stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter
      while PARP-1 displayed strong binding. These interactions were accompanied by
      Cxcl12 downregulation. In the later stages of oxidative stress and intensive
      pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12
      promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12
      expression. The observed ability of PARP-1 to downregulate, and of YY1 to
      upregulate Cxcl12 promoter activity anticipates corresponding effects in the
      natural context where the functional interplay of these proteins could finely
      balance Cxcl12 transcription.

PMID- 23555744
TI  - The HopQ1 effector's nucleoside hydrolase-like domain is required for bacterial
      virulence in arabidopsis and tomato, but not host recognition in tobacco.
AB  - Bacterial pathogens deliver multiple effector proteins into host cells to
      facilitate bacterial growth. HopQ1 is an effector from Pseudomonas syringae pv.
      tomato DC3000 that is conserved across multiple bacterial pathogens which infect
      plants. HopQ1's central region possesses some homology to nucleoside hydrolases,
      but possesses an alternative aspartate motif not found in characterized enzymes.
      A structural model was generated for HopQ1 based on the E. coli RihB nucleoside
      hydrolase and the role of HopQ1's potential catalytic residues for promoting
      bacterial virulence and recognition in Nicotiana tabacum was investigated.
      Transgenic Arabidopsis plants expressing HopQ1 exhibit enhanced disease
      susceptibility to DC3000. HopQ1 can also promote bacterial virulence on tomato
      when naturally delivered from DC3000. HopQ1's nucleoside hydrolase-like domain
      alone is sufficient to promote bacterial virulence, and putative catalytic
      residues are required for virulence promotion during bacterial infection of
      tomato and in transgenic Arabidopsis lines. HopQ1 is recognized and elicits cell
      death when transiently expressed in N. tabacum. Residues required to promote
      bacterial virulence were dispensable for HopQ1's cell death promoting activities
      in N. tabacum. Although HopQ1 has some homology to nucleoside hydrolases, we were
      unable to detect HopQ1 enzymatic activity or nucleoside binding capability using
      standard substrates. Thus, it is likely that HopQ1 promotes pathogen virulence by
      hydrolyzing alternative ribose-containing substrates in planta.

PMID- 23555745
TI  - Impact of financial liberalization on banking sectors performance from central
      and eastern European countries.
AB  - In this paper we analyse the impact of financial liberalization and reforms on
      the banking performance in 17 countries from CEE for the period 2004-2008 using a
      two-stage empirical model that involves estimating bank performance in the first
      stage and assessing its determinants in the second one. From our analysis it
      results that banks from CEE countries with higher level of liberalization and
      openness are able to increase cost efficiency and eventually to offer cheaper
      services to clients. Banks from non-member EU countries are less cost efficient
      but experienced much higher total productivity growth level, and large sized
      banks are much more cost efficient than medium and small banks, while small sized
      banks show the highest growth in terms of productivity.

PMID- 23555746
TI  - Impact of the 3D microenvironment on phenotype, gene expression, and EGFR
      inhibition of colorectal cancer cell lines.
AB  - Three-dimensional (3D) tumor cell cultures grown in laminin-rich-extracellular
      matrix (lrECM) are considered to reflect human tumors more realistic as compared
      to cells grown as monolayer on plastic. Here, we systematically investigated the
      impact of ECM on phenotype, gene expression, EGFR signaling pathway, and on EGFR
      inhibition in commonly used colorectal cancer (CRC) cell lines. LrECM on-top (3D)
      culture assays were performed with the CRC cell lines SW-480, HT-29, DLD-1, LOVO,
      CACO-2, COLO-205 and COLO-206F. Morphology of lrECM cultivated CRC cell lines was
      determined by phase contrast and confocal laser scanning fluorescence microscopy.
      Proliferation of cells was examined by MTT assay, invasive capacity of the cell
      lines was assayed using Matrigel-coated Boyden chambers, and migratory activity
      was determined employing the Fence assay. Differential gene expression was
      analyzed at the transcriptional level by the Agilent array platform. EGFR was
      inhibited by using the specific small molecule inhibitor AG1478. A specific
      spheroid growth pattern was observed for all investigated CRC cell lines. DLD-1,
      HT-29 and SW-480 and CACO-2 exhibited a clear solid tumor cell formation, while
      LOVO, COLO-205 and COLO-206F were characterized by forming grape-like structures.
      Although the occurrence of a spheroid morphology did not correlate with an
      altered migratory, invasive, or proliferative capacity of CRC cell lines, gene
      expression was clearly altered in cells grown on lrECM as compared to 2D
      cultures. Interestingly, in KRAS wild-type cell lines, inhibition of EGFR was
      less effective in lrECM (3D) cultures as compared to 2D cell cultures. Thus,
      comparing both 2D and 3D cell culture models, our data support the influence of
      the ECM on cancer growth. Compared to conventional 2D cell culture, the lrECM
      (3D) cell culture model offers the opportunity to investigate permanent CRC cell
      lines under more physiological conditions, i.e. in the context of molecular
      therapeutic targets and their pharmacological inhibition.

PMID- 23555747
TI  - (3)D [corrected] quantification of tumor vasculature in lymphoma xenografts in
      NOD/SCID mice allows to detect differences among vascular-targeted therapies.
AB  - Quantitative characterization of the in vivo effects of vascular-targeted
      therapies on tumor vessels is hampered by the absence of useful 3D vascular
      network descriptors aside from microvessel density. In this study, we extended
      the quantification of planar vessel distribution to the analysis of vascular
      volumes by studying the effects of antiangiogenic (sorafenib and sunitinib) or
      antivascular (combretastatin A4 phosphate) treatments on the quantity and spatial
      distributions of thin microvessels. These observations were restricted to
      perinecrotic areas of treated human multiple myeloma tumors xenografted in
      immunodeficient mice and to microvessels with an approximate cross-sectional area
      lower than 75 um(2). Finally, vessel skeletonization minimized artifacts due to
      possible differential wall staining and allowed a comparison of the various
      treatment effects. Antiangiogenic drug treatment reduced the number of vessels of
      every caliber (at least 2-fold fewer vessels vs. controls; p<0.001, n = 8) and
      caused a heterogeneous distribution of the remaining vessels. In contrast, the
      effects of combretastatin A4 phosphate mainly appeared to be restricted to a
      homogeneous reduction in the number of thin microvessels (not more than 2-fold
      less vs. controls; p<0.001, n = 8) with marginal effects on spatial distribution.
      Unexpectedly, these results also highlighted a strict relationship between
      microvessel quantity, distribution and cross-sectional area. Treatment-specific
      changes in the curves describing this relationship were consistent with the
      effects ascribed to the different drugs. This finding suggests that our results
      can highlight differences among vascular-targeted therapies, providing hints on
      the processes underlying sample vascularization together with the detailed
      characterization of a pathological vascular tree.

PMID- 23555748
TI  - Human adipose tissue derived mesenchymal stem cells aggravate chronic cyclosporin
      nephrotoxicity by the induction of oxidative stress.
AB  - The aim of this study was to investigate whether hATMSCs protect against
      cyclosporine (CsA)-induced renal injury. CsA (7.5 mg/kg) and hATMSCs (3*10(6)/5
      mL) were administered alone and together to rats for 4 weeks. The effect of
      hATMSCs on CsA-induced renal injury was evaluated by assessing renal function,
      interstitial fibrosis, infiltration of inflammatory cells, and apoptotic cell
      death. Four weeks of CsA-treatment produced typical chronic CsA-nephropathy.
      Combined treatment with CsA and hATMSCs did not prevent these effects and showed
      a trend toward further renal deterioration. To evaluate why hATMSCs aggravated
      CsA-induced renal injury, we measured oxidative stress, a major mechanism of CsA
      induced renal injury. Both urine and serum 8-hydroxydeoxyguanosine(8-OHdG) levels
      were higher in the CsA+hATMSCs group than in the CsA group (P<0.05). An in vitro
      study showed similar results. Although the rate of apoptosis did not differ
      significantly between HK-2 cells cultured in hATMSCs-conditioned medium and those
      cultured in DMEM, addition of CsA resulted in greater apoptosis in HK-2 cells
      cultured in hATMSCs-conditioned medium. Addition of CsA increased oxidative
      stress in the hATMSCs-conditioned medium. The results of our study suggest that
      treatment with hATMSCs may aggravate CsA-induced renal injury because hATMSCs
      cause oxidative stress in the presence of CsA.

PMID- 23555749
TI  - Cardioprotective properties of omentin-1 in type 2 diabetes: evidence from
      clinical and in vitro studies.
AB  - CONTEXT: Adipokines are linked to the development of cardiovascular dysfunction
      in type 2 diabetes (DM2). In DM2-patients, circulating levels of omentin-1, an
      adipokine preferentially expressed in epicardial adipose tissue, are decreased.
      This study investigated whether omentin-1 has a cardioprotective function.
      METHODS: Omentin-1 levels in plasma and cardiac fat depots were determined in DM2
      patients versus controls. Moreover, the relation between omentin-1 levels and
      cardiac function was examined in men with uncomplicated DM2. Finally, we
      determined whether omentin-1 could reverse the induction of cardiomyocyte
      dysfunction by conditioned media derived from epicardial adipose tissue from
      patients with DM2. RESULTS: Omentin-1 was highly expressed and secreted by
      epicardial adipose tissue, and reduced in DM2. Circulating omentin-1 levels were
      lower in DM2 versus controls, and positively correlated with the diastolic
      parameters early peak filling rate, early deceleration peak and early
      deceleration mean (all P<0.05). The improved diastolic function following
      pioglitazone treatment associated with increases in omentin-1 levels (P<0.05). In
      vitro, exposure of cardiomyocytes to conditioned media derived from epicardial
      adipose tissue from patients with DM2 induced contractile dysfunction and insulin
      resistance, which was prevented by the addition of recombinant omentin.
      CONCLUSION: These data identify omentin-1 as a cardioprotective adipokine, and
      indicate that decreases in omentin-1 levels could contribute to the induction of
      cardiovascular dysfunction in DM2.

PMID- 23555750
TI  - Functional analysis and expressional characterization of rice ankyrin repeat
      containing protein, OsPIANK1, in basal defense against Magnaporthe oryzae attack.
AB  - The ankyrin repeat-containing protein gene OsPIANK1 (AK068021) in rice (Oryza
      sativa L.) was previously shown to be upregulated following infection with the
      rice leaf blight pathogen Xanthomonas oryzae pv oryzae (Xoo). In this study, we
      further characterized the role of OsPIANK1 in basal defense against Magnaporthe
      oryzae (M.oryzae) by 5' deletion analysis of its promoter and overexpression of
      the gene. The promoter of OsPIANK1 with 1,985 bps in length was sufficient to
      induce the OsPIANK1 response to inoculation with M.oryzae and to exogenous
      application of methyl jasmonate (MeJA) or salicylic acid (SA), but not to
      exogenous application of abscisic acid (ABA). A TCA-element present in the region
      between -563 bp and -249 bp may be responsible for the OsPIANK1 response to both
      M.oryzae infection and exogenous SA application. The JERE box, CGTCA-box, and two
      MYB binding sites locating in the region between -1985 bp and -907 bp may be
      responsible for the response of OsPIANK1 to exogenous MeJA. OsPIANK1 expression
      was upregulated after inoculation with M.oryzae and after treatment with
      exogenous SA and MeJA. Overexpression of OsPIANK1 enhanced resistance of rice to
      M.oryzae, although it did not confer complete resistance. The enhanced resistance
      to M.oryzae was accompanied by enhanced transcriptional expression of SA- and JA
      dependent genes such as NH1, WKRY13, PAL, AOS2, PR1b, and PR5. This evidence
      suggests that OsPIANK1 acted as a positive regulator in rice basal defense
      mediated by SA- and JA-signaling pathways.

PMID- 23555751
TI  - Eligibility for bevacizumab as an independent prognostic factor for patients with
      advanced non-squamous non-small cell lung cancer: a retrospective cohort study.
AB  - BACKGROUND: Bevacizumab requires some unique eligibility criteria, such as
      absence of hemoptysis and major blood vessel invasion by the tumor. The
      prognostic impact of these bevacizumab-specific criteria has not been evaluated.
      METHODS: Patients with stage IIIB/IV, non-squamous non-small cell lung cancer who
      started chemotherapy before the approval of bevacizumab were reviewed. Patients
      with impaired organ function, poor performance status or untreated/symptomatic
      brain metastasis were excluded before the evaluation of bevacizumab eligibility.
      We compared overall survival and time to treatment failure among patients who
      were eligible (Group A) or ineligible (Group B) to receive bevacizumab. RESULTS:
      Among 283 patients with stage IIIB/IV non-squamous non-small cell lung cancer,
      eligibility for bevacizumab was evaluated in 154 patients. Fifty-seven patients
      were considered ineligible (Group B) based on one or more of a history of
      hemoptysis (n = 20), major blood vessel invasion (n = 43) and cardiovascular
      disease (n = 8). The remaining 97 patients were classified into Group A. Overall
      survival was significantly better in Group A (median, 14.6 months) than in Group
      B (median, 7.1 months; p<0.0001). Time to treatment failure was also
      significantly longer in Group A (median, 6.9 months) than in Group B (median, 3.0
      months; p<0.0001). Adjusted hazard ratios of bevacizumab eligibility for overall
      survival and time to treatment failure were 0.48 and 0.38 (95% confidence
      intervals, 0.33-0.70 and 0.25-0.58), respectively. CONCLUSION: Eligibility for
      bevacizumab itself represents a powerful prognostic factor for patients with non
      squamous non-small cell lung cancer. The proportion of patients who underwent
      first-line chemotherapy without disease progression or unacceptable toxicity can
      also be biased by bevacizumab eligibility. Selection bias can be large in
      clinical trials of bevacizumab, so findings from such trials should be
      interpreted with extreme caution.

PMID- 23555752
TI  - Defining the transcriptional and cellular landscape of type 1 diabetes in the NOD
      mouse.
AB  - Our ability to successfully intervene in disease processes is dependent on
      definitive diagnosis. In the case of autoimmune disease, this is particularly
      challenging because progression of disease is lengthy and multifactorial. Here we
      show the first chronological compendium of transcriptional and cellular
      signatures of diabetes in the non-obese diabetic mouse. Our data relates the
      immunological environment of the islets of Langerhans with the transcriptional
      profile at discrete times. Based on these data, we have parsed diabetes into
      several discrete phases. First, there is a type I interferon signature that
      precedes T cell activation. Second, there is synchronous infiltration of all
      immunological cellular subsets and a period of control. Finally, there is the
      killing phase of the diabetogenic process that is correlated with an NF-kB
      signature. Our data provides a framework for future examination of autoimmune
      diabetes and its disease progression markers.

PMID- 23555753
TI  - Enhancement of inflammatory protein expression and nuclear factor Kappab (NF
      Kappab) activity by trichostatin A (TSA) in OP9 preadipocytes.
AB  - The production of inflammatory proteins such as interleukin-6 (IL-6) by
      preadipocytes and mature adipocytes is closely associated with the impairment of
      systemic glucose homeostasis. However, precisely how the production is regulated
      and the roles of histone deacetylases (HDACs) remain largely unknown. The aim of
      this study was to establish whether HDAC inhibitors affect the expression of
      inflammatory proteins in pre/mature adipocytes, and, if so, to determine the
      mechanism involved. Trichostatin A (TSA), an HDAC inhibitor, enhanced
      lipopolysaccharide (LPS)-induced production of IL-6 in OP9 preadipocytes but not
      the mature adipocytes. Moreover, TSA also enhanced palmitic acid-induced IL-6
      production and the expression of inflammatory genes induced by LPS in
      preadipocytes. Although TSA did not affect TLR4 mRNA expression or the activation
      of MAPKs, a reporter gene assay revealed that the LPS-induced increase in nuclear
      factor kappaB (NF-kappaB) activity was enhanced by TSA. Moreover, TSA increased
      the level of NF-kappaB p65 acetylation at lysine 310 and duration of its
      translocation into the nucleus, which leads to enhancement of NF-kappaB activity
      and subsequently expression of inflammatory genes. These findings shed new light
      on the regulatory roles of HDACs in preadipocytes in the production of
      inflammatory proteins.

PMID- 23555754
TI  - Swedish spring wheat varieties with the rare high grain protein allele of NAM-B1
      differ in leaf senescence and grain mineral content.
AB  - Some Swedish spring wheat varieties have recently been shown to carry a rare
      wildtype (wt) allele of the gene NAM-B1, known to affect leaf senescence and
      nutrient retranslocation to the grain. The wt allele is believed to increase
      grain protein concentration and has attracted interest from breeders since it
      could contribute to higher grain quality and more nitrogen-efficient varieties.
      This study investigated whether Swedish varieties with the wt allele differ from
      varieties with one of the more common, non-functional alleles in order to examine
      the effect of the gene in a wide genetic background, and possibly explain why the
      allele has been retained in Swedish varieties. Forty varieties of spring wheat
      differing in NAM-B1 allele type were cultivated under controlled conditions.
      Senescence was monitored and grains were harvested and analyzed for mineral
      nutrient concentration. Varieties with the wt allele reached anthesis earlier and
      completed senescence faster than varieties with the non-functional allele. The wt
      varieties also had more ears, lighter grains and higher yields of P and K.
      Contrary to previous information on effects of the wt allele, our wt varieties
      did not have increased grain N concentration or grain N yield. In addition,
      temporal studies showed that straw length has decreased but grain N yield has
      remained unaffected over a century of Swedish spring wheat breeding. The faster
      development of wt varieties supports the hypothesis of NAM-B1 being preserved in
      Fennoscandia, with its short growing season, because of accelerated development
      conferred by the NAM-B1 wt allele. Although the possible effects of other gene
      actions were impossible to distinguish, the genetic resource of Fennoscandian
      spring wheats with the wt NAM-B1 allele is interesting to investigate further for
      breeding purposes.

PMID- 23555756
TI  - In-cell protease assay systems based on trans-localizing molecular beacon
      proteins using HCV protease as a model system.
AB  - This study describes a sensitive in-cell protease detection system that enables
      direct fluorescence detection of a target protease and its inhibition inside
      living cells. This live-cell imaging system provides a fluorescent molecular
      beacon protein comprised of an intracellular translocation signal sequence, a
      protease-specific cleavage sequence, and a fluorescent tag sequence(s). The
      molecular beacon protein is designed to change its intracellular localization
      upon cleavage by a target protease, i.e., from the cytosol to a subcellular
      organelle or from a subcellular organelle to the cytosol. Protease activity can
      be monitored at the single cell level, and accordingly the entire cell population
      expressing the protease can be accurately enumerated. The clear cellular change
      in fluorescence pattern makes this system an ideal tool for various life science
      and drug discovery research, including high throughput and high content screening
      applications.

PMID- 23555755
TI  - Nuclear phosphoinositide-specific phospholipase C beta1 controls cytoplasmic CCL2
      mRNA levels in HIV-1 gp120-stimulated primary human macrophages.
AB  - HIV-1 envelope glycoprotein gp120 induces, independently of infection, the
      release of CCL2 from macrophages. In turn, this chemokine acts as an autocrine
      factor enhancing viral replication. In this study, we show for the first time
      that phosphoinositide-specific phospholipase C (PI-PLC) is required for the
      production of CCL2 triggered by gp120 in macrophages. Using a combination of
      confocal laser-scanner microscopy, pharmacologic inhibition, western blotting and
      fluorescence-activated cell sorter analysis, we demonstrate that gp120
      interaction with CCR5 leads to nuclear localization of the PI-PLC beta1 isozyme
      mediated by mitogen-activated protein kinase ERK-1/2. Notably,
      phosphatidylcholine-specific phospholipase C (PC-PLC), previously reported to be
      required for NF-kB-mediated CCL2 production induced by gp120 in macrophages,
      drives both ERK1/2 activation and PI-PLC beta1 nuclear localization induced by
      gp120. PI-PLC beta1 activation through CCR5 is also triggered by the natural
      chemokine ligand CCL4, but independently of ERK1/2. Finally, PI-PLC inhibition
      neither blocks gp120-mediated NF-kB activation nor overall accumulation of CCL2
      mRNA, whereas it decreases CCL2 transcript level in the cytoplasm. These results
      identify nuclear PI-PLC beta1 as a new intermediate in the gp120-triggered PC-PLC
      driven signal transduction pathway leading to CCL2 secretion in macrophages. The
      finding that a concerted gp120-mediated signaling involving both PC- and PI
      specific PLCs is required for the expression of CCL2 in macrophages suggests that
      this signal transduction pathway may also be relevant for the modulation of viral
      replication in these cells. Thus, this study may contribute to identify novel
      targets for therapeutic intervention in HIV-1 infection.

PMID- 23555757
TI  - Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility
      to multiple sclerosis in Sardinia: a molecular dynamics simulation study.
AB  - Sardinia is a major Island in the Mediterranean with a high incidence of multiple
      sclerosis, a chronic autoimmune inflammatory disease of the central nervous
      system. Disease susceptibility in Sardinian population has been associated with
      five alleles of major histocompatibility complex (MHC) class II DRB1 gene. We
      performed 120 ns of molecular dynamics simulation on one predisposing and one
      protective alleles, unbound and in complex with the two relevant peptides: Myelin
      Basic Protein and Epstein Barr Virus derived peptide. In particular we focused on
      the MHC peptide binding groove dynamics. The predisposing allele was found to
      form a stable complex with both the peptides, while the protective allele
      displayed stability only when bound with myelin peptide. The local flexibility of
      the MHC was probed dividing the binding groove into four compartments covering
      the well known peptide anchoring pockets. The predisposing allele in the first
      half cleft exhibits a narrower and more rigid groove conformation in the presence
      of myelin peptide. The protective allele shows a similar behavior, while in the
      second half cleft it displays a narrower and more flexible groove conformation in
      the presence of viral peptide. We further characterized these dynamical
      differences by evaluating H-bonds, hydrophobic and stacking interaction networks,
      finding striking similarities with super-type patterns emerging in other
      autoimmune diseases. The protective allele shows a defined preferential binding
      to myelin peptide, as confirmed by binding free energy calculations. All
      together, we believe the presented molecular analysis could help to design
      experimental assays, supports the molecular mimicry hypothesis and suggests that
      propensity to multiple sclerosis in Sardinia could be partly linked to distinct
      peptide-MHC interaction and binding characteristics of the antigen presentation
      mechanism.

PMID- 23555758
TI  - Enhanced functional connectivity between putamen and supplementary motor area in
      Parkinson's disease patients.
AB  - Parkinson's disease (PD) is a surprisingly heterogeneous disorder with symptoms
      including resting tremor, bradykinesia and rigidity. PD has been associated with
      abnormal task related brain activation in sensory and motor regions as well as
      reward related network. Although corticostriatal skeletomotor circuit dysfunction
      is implicated in the neurobiology of Parkinson's disease, the functional
      connectivity within this circuit at the resting state is still unclear for PD.
      Here we utilized resting state functional magnetic resonance imaging to measure
      the functional connectivity of striatum and motor cortex in 19 patients with PD
      and 20 healthy controls. We found that the putamen, but not the caudate,
      exhibited enhanced connectivity with supplementary motor area (SMA), using either
      the putamen or the SMA as the "seed region". Enhanced SMA-amygdala functional
      connectivity was also found in the PD group, compared with normal controls. Our
      findings highlight the key role of hyper-connected putamen-SMC circuit in the
      pathophysiology of PD.

PMID- 23555759
TI  - High-throughput carrier screening using TaqMan allelic discrimination.
AB  - Members of the Ashkenazi Jewish community are at an increased risk for
      inheritance of numerous genetic diseases such that carrier screening is medically
      recommended. This paper describes the development and evaluation of 30 TaqMan
      allelic discrimination qPCR assays for 29 mutations on 2 different high
      throughput platforms. Four of these mutations are in the GBA gene and are
      successfully examined using short amplicons due to the qualitative nature of
      TaqMan allelic discrimination. Two systems were tested for their reliability
      (call rate) and consistency with previous diagnoses (diagnostic accuracy)
      indicating a call rate of 99.04% and a diagnostic accuracy of 100% (+/-0.00%)
      from one platform, and a call rate of 94.66% and a diagnostic accuracy of 93.35%
      (+/-0.29%) from a second for 9,216 genotypes. Results for mutations tested at the
      expected carrier frequency indicated a call rate of 97.87% and a diagnostic
      accuracy of 99.96% (+/-0.05%). This study demonstrated the ability of a high
      throughput qPCR methodology to accurately and reliably genotype 29 mutations in
      parallel. The universally applicable nature of this technology provides an
      opportunity to increase the number of mutations that can be screened
      simultaneously, and reduce the cost and turnaround time for accommodating newly
      identified and clinically relevant mutations.

PMID- 23555760
TI  - Human parvovirus B19 NS1 protein aggravates liver injury in NZB/W F1 mice.
AB  - Human parvovirus B19 (B19) has been associated with a variety of diseases.
      However, the influence of B19 viral proteins on hepatic injury in SLE is still
      obscure. To elucidate the effects of B19 viral proteins on livers in SLE,
      recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W
      F1 mice, respectively. Significant expressions of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19
      NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and
      lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19
      NS1 as compared to those mice receiving PBS. Additionally, significant increases
      of Tumor Necrosis Factor -alpha (TNF-alpha), TNF-alpha receptor, IkappaB kinase 
      alpha (IKK-alpha), nuclear factor of kappa light polypeptide gene enhancer in B
      cells inhibitor (IkappaB) and nuclear factor-kappa B (NF-kappaB) were detected in
      livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving
      PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and
      U-plasminogen activator (uPA) were also detected in livers from NZB/W F1 mice
      receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no
      significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was
      observed as compared to those mice receiving PBS. These findings firstly
      demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on
      hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic
      injury in SLE.

PMID- 23555762
TI  - Imaging beads-retained prey assay for rapid and quantitative protein-protein
      interaction.
AB  - Conventional Western blot based pull-down methods involve lengthy and laborious
      work and the results are generally not quantitative. Here, we report the imaging
      beads-retained prey (IBRP) assay that is rapid and quantitative in studying
      protein-protein interactions. In this assay, the bait is immobilized onto beads
      and the prey is fused with a fluorescence protein. The assay takes advantage of
      the fluorescence of prey and directly quantifies the amount of prey binding to
      the immobilized bait under a microscope. We validated the assay using previously
      well studied interactions and found that the amount of prey retained on beads
      could have a relative linear relationship to both the inputs of bait and prey.
      IBRP assay provides a universal, fast, quantitative and economical method to
      study protein interactions and it could be developed to a medium- or high
      throughput compatible method. With the availability of fluorescence tagged whole
      genome ORFs in several organisms, we predict IBRP assay should have wide
      applications.

PMID- 23555761
TI  - PPARbeta/delta regulates glucocorticoid- and sepsis-induced FOXO1 activation and
      muscle wasting.
AB  - FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part
      reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1
      expression in muscle wasting are poorly understood. We hypothesized that the
      transcription factor peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) upregulates muscle FOXO1 expression and activity with a
      downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and
      glucocorticoid treatment and that inhibition of PPARbeta/delta activity can
      prevent muscle wasting. We found that activation of PPARbeta/delta in cultured
      myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein
      degradation and myotube atrophy. Treatment of myotubes with dexamethasone
      increased PPARbeta/delta expression and activity. Dexamethasone-induced FOXO1
      activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube
      atrophy were inhibited by PPARbeta/delta blocker or siRNA. Importantly, muscle
      wasting induced in rats by dexamethasone or sepsis was prevented by treatment
      with a PPARbeta/delta inhibitor. The present results suggest that PPARbeta/delta
      regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting
      and that treatment with a PPARbeta/delta inhibitor may ameliorate loss of muscle
      mass in these conditions.

PMID- 23555763
TI  - End-point variability is not noise in saccade adaptation.
AB  - When each of many saccades is made to overshoot its target, amplitude gradually
      decreases in a form of motor learning called saccade adaptation. Overshoot is
      induced experimentally by a secondary, backwards intrasaccadic target step (ISS)
      triggered by the primary saccade. Surprisingly, however, no study has compared
      the effectiveness of different sizes of ISS in driving adaptation by
      systematically varying ISS amplitude across different sessions. Additionally,
      very few studies have examined the feasibility of adaptation with relatively
      small ISSs. In order to best understand saccade adaptation at a fundamental
      level, we addressed these two points in an experiment using a range of small,
      fixed ISS values (from 0 degrees  to 1 degrees  after a 10 degrees  primary
      target step). We found that significant adaptation occurred across subjects with
      an ISS as small as 0.25 degrees . Interestingly, though only adaptation in
      response to 0.25 degrees  ISSs appeared to be complete (the magnitude of change
      in saccade amplitude was comparable to size of the ISS), further analysis
      revealed that a comparable proportion of the ISS was compensated for across
      conditions. Finally, we found that ISS size alone was sufficient to explain the
      magnitude of adaptation we observed; additional factors did not significantly
      improve explanatory power. Overall, our findings suggest that current assumptions
      regarding the computation of saccadic error may need to be revisited.

PMID- 23555765
TI  - The response of cerebral cortex to haemorrhagic damage: experimental evidence
      from a penetrating injury model.
AB  - Understanding the response of the brain to haemorrhagic damage is important in
      haemorrhagic stroke and increasingly in the understanding the cerebral
      degeneration and dementia that follow head trauma and head-impact sports. In
      addition, there is growing evidence that haemorrhage from small cerebral vessels
      is important in the pathogenesis of age-related dementia (Alzheimer's disease).
      In a penetration injury model of rat cerebral cortex, we have examined the
      neuropathology induced by a needlestick injury, with emphasis on features
      prominent in the ageing and dementing human brain, particularly plaque-like
      depositions and the expression of related proteins. Needlestick lesions were made
      in neo- and hippocampal cortex in Sprague Dawley rats aged 3-5 months. Brains
      were examined after 1-30 d survival, for haemorrhage, for the expression of
      hyperphosphorylated tau, Abeta, amyloid precursor protein (APP), for gliosis and
      for neuronal death. Temporal cortex from humans diagnosed with Alzheimer's
      disease was examined with the same techniques. Needlestick injury induced long
      lasting changes-haem deposition, cell death, plaque-like deposits and glial
      invasion-along the needle track. Around the track, the lesion induced more
      transient changes, particularly upregulation of Abeta, APP and hyperphosporylated
      tau in neurons and astrocytes. Reactions were similar in hippocampus and
      neocortex, except that neuronal death was more widespread in the hippocampus. In
      summary, experimental haemorrhagic injury to rat cerebral cortex induced both
      permanent and transient changes. The more permanent changes reproduced features
      of human senile plaques, including the formation of extracellular deposits in
      which haem and Abeta-related proteins co-localised, neuronal loss and gliosis.
      The transient changes, observed in tissue around the direct lesion, included the
      upregulation of Abeta, APP and hyperphosphorylated tau, not associated with cell
      death. The findings support the possibility that haemorrhagic damage to the brain
      can lead to plaque-like pathology.

PMID- 23555764
TI  - Bapineuzumab alters abeta composition: implications for the amyloid cascade
      hypothesis and anti-amyloid immunotherapy.
AB  - The characteristic neuropathological changes associated with Alzheimer's disease
      (AD) and other lines of evidence support the amyloid cascade hypothesis. Viewing
      amyloid deposits as the prime instigator of dementia has now led to clinical
      trials of multiple strategies to remove or prevent their formation. We performed
      neuropathological and biochemical assessments of 3 subjects treated with
      bapineuzumab infusions. Histological analyses were conducted to quantify amyloid
      plaque densities, Braak stages and the extent of cerebral amyloid angiopathy
      (CAA). Amyloid-beta (Abeta) species in frontal and temporal lobe samples were
      quantified by ELISA. Western blots of amyloid-beta precursor protein (AbetaPP)
      and its C-terminal (CT) fragments as well as tau species were performed.
      Bapineuzumab-treated (Bapi-AD) subjects were compared to non-immunized age
      matched subjects with AD (NI-AD) and non-demented control (NDC) cases. Our study
      revealed that Bapi-AD subjects exhibited overall amyloid plaque densities similar
      to those of NI-AD cases. In addition, CAA was moderate to severe in NI-AD and
      Bapi-AD patients. Although histologically-demonstrable leptomeningeal,
      cerebrovascular and neuroparenchymal-amyloid densities all appeared unaffected by
      treatment, Abeta peptide profiles were significantly altered in Bapi-AD subjects.
      There was a trend for reduction in total Abeta42 levels as well as an increase in
      Abeta40 which led to a corresponding significant decrease in Abeta42:Abeta40
      ratio in comparison to NI-AD subjects. There were no differences in the levels of
      AbetaPP, CT99 and CT83 or tau species between Bapi-AD and NI-AD subjects. The
      remarkable alteration in Abeta profiles reveals a dynamic amyloid production in
      which removal and depositional processes were apparently perturbed by
      bapineuzumab therapy. Despite the alteration in biochemical composition, all 3
      immunized subjects exhibited continued cognitive decline.

PMID- 23555766
TI  - Mobile phone use, blood lead levels, and attention deficit hyperactivity symptoms
      in children: a longitudinal study.
AB  - BACKGROUND: Concerns have developed for the possible negative health effects of
      radiofrequency electromagnetic field (RF-EMF) exposure to children's brains. The
      purpose of this longitudinal study was to investigate the association between
      mobile phone use and symptoms of Attention Deficit Hyperactivity Disorder (ADHD)
      considering the modifying effect of lead exposure. METHODS: A total of 2,422
      children at 27 elementary schools in 10 Korean cities were examined and followed
      up 2 years later. Parents or guardians were administered a questionnaire
      including the Korean version of the ADHD rating scale and questions about mobile
      phone use, as well as socio-demographic factors. The ADHD symptom risk for mobile
      phone use was estimated at two time points using logistic regression and combined
      over 2 years using the generalized estimating equation model with repeatedly
      measured variables of mobile phone use, blood lead, and ADHD symptoms, adjusted
      for covariates. RESULTS: The ADHD symptom risk associated with mobile phone use
      for voice calls but the association was limited to children exposed to relatively
      high lead. CONCLUSIONS: The results suggest that simultaneous exposure to lead
      and RF from mobile phone use was associated with increased ADHD symptom risk,
      although possible reverse causality could not be ruled out.

PMID- 23555767
TI  - Surveillance on the status of immune cells after Echinnococcus granulosus
      protoscoleces infection in Balb/c mice.
AB  - BACKGROUND: Cystic echinococcosis is a global parasitic disease caused by
      infection with Echinococcus granulosus larvae with potentially life-threatening
      complications in humans. To date, the status of the immune cells believed to be
      associated with the pathogenicity of E. granulosus infection has not been
      demonstrated clearly. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed
      a multiplex flow cytometry assay to investigate the systemic immune status of
      innate and adaptive immunity at 30, 180, 360 days post-infection (dpi) in mice
      infected with E. granulousus. At 30 dpi, an increase in the number of CD11b(+)
      and CD11c(+) antigen-presenting cells (APCs) was observed. This was accompanied
      by the slight down-regulated expression of the co-stimulatory molecule MHC-II,
      indicating the impairment of APCs in early infection through the release of
      secretory-excretory products. In all infected groups, we observed a significant
      increase in innate immune cells, including APCs and GR-1(+) cells, and a dramatic
      increase in the myeloid-derived suppressor cells (MDSC) expressing CD11b(+)/GR
      1(+). Moreover, the upregulation of the activated markers CD69, CD44, CD40L, and
      the downregulation of CD62L were observed in the CD4(+) and CD8(+) T cells
      following infection. Regulatory T cells expressing CD4(+)/CD25(+)/FoxP3 (+)
      increased significantly over the course of infection. CONCLUSIONS: Our findings
      demonstrate that the microenvironment in the peripheral immune system after E.
      granulosus infection changes in subtle but detectably ways, especially during the
      persistent period of infection. We found that T cells were activated following
      infection, but observed that the significant increase of immunosuppressive cells
      such as MDSC and Treg cells could inhibit T cell response to E. granulosus
      antigens. We suggest these cells may play a neglected but key role in the
      downregulation of the immune response in long-term parasitic infection.
      Understanding the basic functions and temporal interactions of these
      immunosuppressive cells will pave the way for new strategies of parasite vaccine
      design.

PMID- 23555768
TI  - Expression and functional heterogeneity of chemokine receptors CXCR4 and CXCR7 in
      primary patient-derived glioblastoma cells.
AB  - Glioblastoma (GBM) is the most common primary brain tumor in adults. The poor
      prognosis and minimally successful treatments of these tumors indicates a need to
      identify new therapeutic targets. Therapy resistance of GBMs is attributed to
      heterogeneity of the glioblastoma due to genetic alterations and functional
      subpopulations. Chemokine receptors CXCR4 and CXCR7 play important roles in
      progression of various cancers although the specific functions of the CXCL12
      CXCR4-CXCR7 axis in GBM are less characterized. In this study we examined the
      expression and function of CXCR4 and CXCR7 in four primary patient-derived GBM
      cell lines of the proliferative subclass, investigating their roles in in vitro
      growth, migration, sphere and tube formation. CXCR4 and CXCR7 cell surface
      expression was heterogeneous both between and within each cell line examined,
      which was not reflected by RT-PCR analysis. Variable percentages of CXCR4+CXCR7-
      (CXCR4 single positive), CXCR4-CXCR7+ (CXCR7 single positive), CXCR4+CXCR7+
      (double positive), and CXCR4-CXCR7- (double negative) subpopulations were evident
      across the lines examined. A subpopulation of slow cell cycling cells was
      enriched in CXCR4 and CXCR7. CXCR4+, CXCR7+, and CXCR4+/CXCR7+ subpopulations
      were able to initiate intracranial tumors in vivo. CXCL12 stimulated in vitro
      cell growth, migration, sphere formation and tube formation in some lines and,
      depending on the response, the effects were mediated by either CXCR4 or CXCR7.
      Collectively, our results indicate a high level of heterogeneity in both the
      surface expression and functions of CXCR4 and CXCR7 in primary human GBM cells of
      the proliferative subclass. Should targeting of CXCR4 and CXCR7 provide clinical
      benefits to GBM patients, a personalized treatment approach should be considered
      given the differential expression and functions of these receptors in GBM.

PMID- 23555769
TI  - Elevated PLA2G7 gene promoter methylation as a gender-specific marker of aging
      increases the risk of coronary heart disease in females.
AB  - PLA2G7 gene product is a secreted enzyme whose activity is associated with
      coronary heart disease (CHD). The goal of our study is to investigate the
      contribution of PLA2G7 promoter DNA methylation to the risk of CHD. Using the
      bisulphite pyrosequencing technology, PLA2G7 methylation was measured among 36
      CHD cases and 36 well-matched controls. Our results indicated that there was a
      significant association between PLA2G7 methylation and CHD (adjusted P = 0.025).
      Significant gender-specific correlation was observed between age and PLA2G7
      methylation (males: adjusted r = -0.365, adjusted P = 0.037; females: adjusted r
      = 0.373, adjusted P = 0.035). A breakdown analysis by gender showed that PLA2G7
      methylation was significantly associated with CHD in females (adjusted P = 0.003)
      but not in males. A further two-way ANOVA analysis showed there was a significant
      interaction between gender and status of CHD for PLA2G7 methylation (gender*CHD:
      P = 6.04E-7). Moreover, PLA2G7 methylation is associated with the levels of total
      cholesterols (TC, r = 0.462, P = 0.009), triglyceride (TG, r = 0.414, P = 0.02)
      and Apolipoprotein B (ApoB, r = 0.396, P = 0.028) in females but not in males
      (adjusted P>0.4). Receiver operating characteristic (ROC) curves showed that
      PLA2G7 methylation could predict the risk of CHD in females (area under curve
      (AUC) = 0.912, P = 2.40E-5). Our results suggest that PLA2G7 methylation changes
      with aging in a gender-specific pattern. The correlation between PLA2G7
      methylation and CHD risk in females is independent of other parameters including
      age, smoking, diabetes and hypertension. PLA2G7 methylation might exert its
      effects on the risk of CHD by regulating the levels of TC, TG, and ApoB in
      females. The gender disparities in the PLA2G7 methylation may play a role in the
      molecular mechanisms underlying the pathophysiology of CHD.

PMID- 23555771
TI  - How far could the alien boatman Trichocorixa verticalis verticalis spread?
      Worldwide estimation of its current and future potential distribution.
AB  - Invasions of alien species are considered among the least reversible human
      impacts, with diversified effects on aquatic ecosystems. Since prevention is the
      most cost-effective way to avoid biodiversity loss and ecosystem problems, one
      challenge in ecological research is to understand the limits of the fundamental
      niche of the species in order to estimate how far invasive species could spread.
      Trichocorixa verticalis verticalis (Tvv) is a corixid (Hemiptera) originally
      distributed in North America, but cited as an alien species in three continents.
      Its impact on native communities is under study, but it is already the dominant
      species in several saline wetlands and represents a rare example of an aquatic
      alien insect. This study aims: i) to estimate areas with suitable environmental
      conditions for Tvv at a global scale, thus identifying potential new zones of
      invasion; and ii) to test possible changes in this global potential distribution
      under a climate change scenario. Potential distributions were estimated by
      applying a multidimensional envelope procedure based on both climatic data,
      obtained from observed occurrences, and thermal physiological data. Our results
      suggest Tvv may expand well beyond its current range and find inhabitable
      conditions in temperate areas along a wide range of latitudes, with an emphasis
      on coastal areas of Europe, Northern Africa, Argentina, Uruguay, Australia, New
      Zealand, Myanmar, India, the western boundary between USA and Canada, and areas
      of the Arabian Peninsula. When considering a future climatic scenario, the
      suitability area of Tvv showed only limited changes compared with the current
      potential distribution. These results allow detection of potential contact zones
      among currently colonized areas and potential areas of invasion. We also
      identified zones with a high level of suitability that overlap with areas
      recognized as global hotspots of biodiversity. Finally, we present hypotheses
      about possible means of spread, focusing on different geographical scales.

PMID- 23555770
TI  - Evidences of early senescence in multiple myeloma bone marrow mesenchymal stromal
      cells.
AB  - BACKGROUND: In multiple myeloma, bone marrow mesenchymal stromal cells support
      myeloma cell growth. Previous studies have suggested that direct and indirect
      interactions between malignant cells and bone marrow mesenchymal stromal cells
      result in constitutive abnormalities in the bone marrow mesenchymal stromal
      cells. DESIGN AND METHODS: The aims of this study were to investigate the
      constitutive abnormalities in myeloma bone marrow mesenchymal stromal cells and
      to evaluate the impact of new treatments. RESULTS: We demonstrated that myeloma
      bone marrow mesenchymal stromal cells have an increased expression of senescence
      associated beta-galactosidase, increased cell size, reduced proliferation
      capacity and characteristic expression of senescence-associated secretory profile
      members. We also observed a reduction in osteoblastogenic capacity and
      immunomodulatory activity and an increase in hematopoietic support capacity.
      Finally, we determined that current treatments were able to partially reduce some
      abnormalities in secreted factors, proliferation and osteoblastogenesis.
      CONCLUSIONS: We showed that myeloma bone marrow mesenchymal stromal cells have an
      early senescent profile with profound alterations in their characteristics. This
      senescent state most likely participates in disease progression and relapse by
      altering the tumor microenvironment.

PMID- 23555772
TI  - Purification and characterization of Shiga toxin 2f, an immunologically unrelated
      subtype of Shiga toxin 2.
AB  - BACKGROUND: Shiga-like toxin 2 (Stx2) is one of the most important virulence
      factors in enterohaemorrhagic Escherichia coli (E. coli) strains such as O157H7.
      Subtypes of Stx2 are diverse with respect to their sequence, toxicity, and
      distribution. The most diverse Stx2 subtype, Stx2f, is difficult to detect
      immunologically, but is becoming more frequently associated with human illness.
      METHODS AND FINDINGS: A purification regimen was developed for the purification
      of Stx2f involving cation exchange, hydrophobic interaction, anion exchange, and
      gel filtration. The molecular weight of Stx2f B-subunit was approximately 5 kDa,
      which appeared significantly smaller than that of Stx2a (6 kDa) on a SDS-PAGE
      gel, although the size of the A subunit was similar to Stx2a (30 kDa). Stx2f was
      shown to be active in both cell-free and cell-based assays. The 50% cytotoxic
      dose in Vero cells was 3.4 or 1.7 pg (depending on the assay conditions), about 3
      5 times higher than the archetypical Stx2a, while the activity of Stx2f and Stx2a
      in a cell-free rabbit reticulocyte system was similar. Stx2f bound to both
      globotriose-lipopolysaccharide (Gb3-LPS) and globotetraose-LPS (Gb4-LPS, mimics
      for globotriaosylceramide and globotetraosylceramide, respectively), but its
      ability to bind Gb4-LPS was much stronger than Stx2a. Stx2f was also much more
      stable at low pH and high temperature compared to Stx2a, suggesting the toxin
      itself may survive harsher food preparation practices. CONCLUSIONS: Here, we
      detail the purification, biochemical properties, and toxicity of Stx2f, from an
      E. coli strain isolated from a feral pigeon. Information obtained in this study
      will be valuable for characterizing Stx2f and explaining the differences of Stx2a
      and Stx2f in host specificity and cytotoxicity.

PMID- 23555773
TI  - Understanding the specificity of human Galectin-8C domain interactions with its
      glycan ligands based on molecular dynamics simulations.
AB  - Human Galectin-8 (Gal-8) is a member of the galectin family which shares an
      affinity for beta-galactosides. The tandem-repeat Gal-8 consists of a N- and a C
      terminal carbohydrate recognition domain (N- and C-CRD) joined by a linker
      peptide of various length. Despite their structural similarity both CRDs
      recognize different oligosaccharides. While the molecular requirements of the N
      CRD for high binding affinity to sulfated and sialylated glycans have recently
      been elucidated by crystallographic studies of complexes with several
      oligosaccharides, the binding specificities of the C-CRD for a different set of
      oligosaccharides, as derived from experimental data, has only been explained in
      terms of the three-dimensional structure for the complex C-CRD with lactose. In
      this study we performed molecular dynamics (MD) simulations using the recently
      released crystal structure of the Gal-8C-CRD to analyse the three-dimensional
      conditions for its specific binding to a variety of oligosaccharides as
      previously defined by glycan-microarray analysis. The terminal beta-galactose of
      disaccharides (LacNAc, lacto-N-biose and lactose) and the internal beta-galactose
      moiety of blood group antigens A and B (BGA, BGB) as well as of longer linear
      oligosaccharide chains (di-LacNAc and lacto-N-neotetraose) are interacting
      favorably with conserved amino acids (H53, R57, N66, W73, E76). Lacto-N
      neotetraose and di-LacNAc as well as BGA and BGB are well accommodated. BGA and
      BGB showed higher affinity than LacNAc and lactose due to generally stronger
      hydrogen bond interactions and water mediated hydrogen bonds with alpha1-2 fucose
      respectively. Our results derived from molecular dynamics simulations are able to
      explain the glycan binding specificities of the Gal-8C-CRD in comparison to those
      of the Gal-8N -CRD.

PMID- 23555774
TI  - CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity
      during acute and early infection.
AB  - The strong CD8+ T-cell-mediated HIV-1-suppressive capacity found in a minority of
      HIV-infected patients in chronic infection is associated with spontaneous control
      of viremia. However, it is still unclear whether such capacities were also
      present earlier in the CD8+ T cells from non controller patients and then lost as
      a consequence of uncontrolled viral replication. We studied 50 patients with
      primary HIV-1-infection to determine whether strong CD8+ T-cell-mediated HIV
      suppression is more often observed at that time. Despite high frequencies of
      polyfunctional HIV-specific CD8+ T-cells and a strong CD4+ T-helper response,
      CD8+ T-cells from 48 patients lacked strong HIV-suppressive capacities ex vivo.
      This indicates that the superior HIV-suppressive capacity of CD8+ T-cells from
      HIV controllers is not a general characteristic of the HIV-specific CD8+ T cell
      response in primary HIV infection.

PMID- 23555775
TI  - T2 values of posterior horns of knee menisci in asymptomatic subjects.
AB  - PURPOSE: The magnetic resonance (MR) T2 value of cartilage is a reliable
      indicator of tissue properties and therefore may be used as an objective
      diagnostic tool in early meniscal degeneration. The purpose of this study was to
      investigate age, gender, location, and zonal differences in MR T2 value of the
      posterior horns of knee menisci in asymptomatic subjects. METHODS: Sixty
      asymptomatic volunteers (30 men and 30 women) were enrolled and divided into
      three different age groups: 20-34, 35-49 and 50-70 years. The inclusion criteria
      were BMI<30 kg/cm(2), normalized Western Ontario and McMaster Universities
      (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous
      abnormalities on routine knee MR imaging. The T2 values were measured on images
      acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T.
      RESULTS: The mean T2 values in both medial and lateral menisci for the 20-34, 35
      49, and 50-70 age groups were 9.94 msec+/-0.94, 10.73 msec+/-1.55, and 12.36
      msec+/-2.27, respectively, for women and 9.17 msec+/-0.74, 9.64 msec+/-0.67, and
      10.95 msec+/-1.33, respectively, for men. The T2 values were significantly higher
      in the 50-70 age group than the 20-34 age group (P<0.001) and in women than in
      men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were
      significantly higher in medial menisci than in lateral menisci only in women age
      50-70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50
      70 and 35-49 age groups than that of the 20-34 age group (2.47, 1.02; 2.77, 1.16
      msec, respectively, all P<0.01). CONCLUSION: The MR T2 values of the posterior
      meniscal horns increase with increasing age in women and are higher in women than
      in men. The age-related rise of T2 values appears to be more severe in medial
      menisci than in lateral menisci. Differences exist in the white zone and
      red/white zone.

PMID- 23555776
TI  - The clinical significance of the CD163+ and CD68+ macrophages in patients with
      hepatocellular carcinoma.
AB  - Our previous study has found that the abundance of peritumoral CD68(+)
      macrophages was associated with poor prognosis in hepatocellular carcinoma (HCC)
      after resection. However, CD68 staining could not discriminate the protumoral or
      tumoricidal subpopulations from pan-macrophages. CD163 is a marker of
      alternatively activated macrophages. In this study, the clinical significance of
      CD163(+) cells in tumors and peritumoral liver tissues was evaluated in a cohort
      of 295 patients with HCC after curative resection. We found that the density of
      CD163(+) cells was well correlated with that of CD68(+) cells in both tumors and
      peritumoral liver tissues but was much more. Immunostaining on consecutive
      sections and flow cytometry assay on surgical resected specimens further
      supported the findings that the CD163(+) cells was more abundant than CD68(+)
      cells. The density of peritumoral CD68(+) cells was associated with poor
      recurrence-free survival (RFS) and poor overall survival (OS) (P = 0.004 and P =
      0.001, respectively), whereas the CD163(+) cells have no prognostic values either
      in tumors or in peritumoral liver tissues. In another cohort of 107 HCC patients,
      preoperative plasma concentration of soluble form of CD163 (sCD163) was
      associated with active hepatitis-related factors but not associated with the
      markers of tumor invasion. In conclusion, both the CD163(+) cells local
      infiltration and plasma sCD163 were of limited significance in HCC, and they were
      more likely markers related to active hepatitis rather than tumor progression.

PMID- 23555777
TI  - Bloodstream infection among adults in Phnom Penh, Cambodia: key pathogens and
      resistance patterns.
AB  - BACKGROUND: Bloodstream infections (BSI) cause important morbidity and mortality
      worldwide. In Cambodia, no surveillance data on BSI are available so far.
      METHODS: From all adults presenting with SIRS at Sihanouk Hospital Centre of HOPE
      (July 2007-December 2010), 20 ml blood was cultured. Isolates were identified
      using standard microbiological techniques; antibiotic susceptibilities were
      assessed using disk diffusion and MicroScan(r), with additional E-test, D-test
      and double disk test where applicable, according to CLSI guidelines. RESULTS: A
      total of 5714 samples from 4833 adult patients yielded 501 clinically significant
      organisms (8.8%) of which 445 available for further analysis. The patients'
      median age was 45 years (range 15-99 y), 52.7% were women. HIV-infection and
      diabetes were present in 15.6% and 8.8% of patients respectively. The overall
      mortality was 22.5%. Key pathogens included Escherichia coli (n = 132; 29.7%),
      Salmonella spp. (n = 64; 14.4%), Burkholderia pseudomallei (n = 56; 12.6%) and
      Staphylococcus aureus (n = 53; 11.9%). Methicillin resistance was seen in 10/46
      (21.7%) S. aureus; 4 of them were co-resistant to erythromycin, clindamycin,
      moxifloxacin and sulphamethoxazole-trimethoprim (SMX-TMP). We noted combined
      resistance to amoxicillin, SMX-TMP and ciprofloxacin in 81 E. coli isolates
      (62.3%); 62 isolates (47.7%) were confirmed as producers of extended spectrum
      beta-lactamase. Salmonella isolates displayed high rates of multidrug resistance
      (71.2%) with high rates of decreased ciprofloxacin susceptibility (90.0%) in
      Salmonella Typhi while carbapenem resistance was observed in 5.0% of 20
      Acinetobacter sp. isolates. CONCLUSIONS: BSI in Cambodian adults is mainly caused
      by difficult-to-treat pathogens. These data urge for microbiological capacity
      building, nationwide surveillance and solid interventions to contain antibiotic
      resistance.

PMID- 23555778
TI  - Sodium laurate, a novel protease- and mass spectrometry-compatible detergent for
      mass spectrometry-based membrane proteomics.
AB  - The hydrophobic nature of most membrane proteins severely complicates their
      extraction, proteolysis and identification. Although detergents can be used to
      enhance the solubility of the membrane proteins, it is often difficult for a
      detergent not only to have a strong ability to extract membrane proteins, but
      also to be compatible with the subsequent proteolysis and mass spectrometric
      analysis. In this study, we made evaluation on a novel application of sodium
      laurate (SL) to the shotgun analysis of membrane proteomes. SL was found not only
      to lyse the membranes and solubilize membrane proteins as efficiently as SDS, but
      also to be well compatible with trypsin and chymotrypsin. Furthermore, SL could
      be efficiently removed by phase transfer method from samples after acidification,
      thus ensuring not to interfere with the subsequent CapLC-MS/MS analysis of the
      proteolytic peptides of proteins. When SL was applied to assist the digestion and
      identification of a standard protein mixture containing bacteriorhodoposin and
      the proteins in rat liver plasma membrane-enriched fractions, it was found that,
      compared with other two representative enzyme- and MS-compatible detergents
      RapiGest SF (RGS) and sodium deoxycholate (SDC), SL exhibited obvious superiority
      in the identification of membrane proteins particularly those with high
      hydrophobicity and/or multiple transmembrane domains.

PMID- 23555780
TI  - A computational study of the hydrodynamics in the nasal region of a hammerhead
      shark (Sphyrna tudes): implications for olfaction.
AB  - The hammerhead shark possesses a unique head morphology that is thought to
      facilitate enhanced olfactory performance. The olfactory chambers, located at the
      distal ends of the cephalofoil, contain numerous lamellae that increase the
      surface area for olfaction. Functionally, for the shark to detect chemical
      stimuli, water-borne odors must reach the olfactory sensory epithelium that lines
      these lamellae. Thus, odorant transport from the aquatic environment to the
      sensory epithelium is the first critical step in olfaction. Here we investigate
      the hydrodynamics of olfaction in Sphyrna tudes based on an anatomically-accurate
      reconstruction of the head and olfactory chamber from high-resolution micro-CT
      and MRI scans of a cadaver specimen. Computational fluid dynamics simulations of
      water flow in the reconstructed model reveal the external and internal
      hydrodynamics of olfaction during swimming. Computed external flow patterns
      elucidate the occurrence of flow phenomena that result in high and low pressures
      at the incurrent and excurrent nostrils, respectively, which induces flow through
      the olfactory chamber. The major (prenarial) nasal groove along the cephalofoil
      is shown to facilitate sampling of a large spatial extent (i.e., an extended
      hydrodynamic "reach") by directing oncoming flow towards the incurrent nostril.
      Further, both the major and minor nasal grooves redirect some flow away from the
      incurrent nostril, thereby limiting the amount of fluid that enters the olfactory
      chamber. Internal hydrodynamic flow patterns are also revealed, where we show
      that flow rates within the sensory channels between olfactory lamellae are
      passively regulated by the apical gap, which functions as a partial bypass for
      flow in the olfactory chamber. Consequently, the hammerhead shark appears to
      utilize external (major and minor nasal grooves) and internal (apical gap) flow
      regulation mechanisms to limit water flow between the olfactory lamellae, thus
      protecting these delicate structures from otherwise high flow rates incurred by
      sampling a larger area.

PMID- 23555779
TI  - Vitiligo: a possible model of degenerative diseases.
AB  - Vitiligo is characterized by the progressive disappearance of pigment cells from
      skin and hair follicle. Several in vitro and in vivo studies show evidence of an
      altered redox status, suggesting that loss of cellular redox equilibrium might be
      the pathogenic mechanism in vitiligo. However, despite the numerous data
      supporting a pathogenic role of oxidative stress, there is still no consensus
      explanation underlying the oxidative stress-driven disappear of melanocytes from
      the epidermis. In this study, in vitro characterization of melanocytes cultures
      from non-lesional vitiligo skin revealed at the cellular level aberrant function
      of signal transduction pathways common with neurodegenerative diseases including
      modification of lipid metabolism, hyperactivation of mitogen-activated protein
      kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53
      dependent stress signal transduction cascades, and enhanced sensibility to pro
      apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative
      stress are also biomarkers of pre-senescent cellular phenotype. Consistent with
      this, vitiligo cells showed a significant increase in p16 that did not correlate
      with the chronological age of the donor. Moreover, vitiligo melanocytes produced
      many biologically active proteins among the senescence-associated secretory
      phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3
      (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3
      and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated
      pathophysiologic puzzle underlying melanocytes degeneration resembling, from the
      biological point of view, neurodegenerative diseases. Our results suggest new
      possible targets for intervention that in combination with current therapies
      could correct melanocytes intrinsic defects.

PMID- 23555781
TI  - Inhibition of dopamine transporter activity by G protein betagamma subunits.
AB  - Uptake through the Dopamine Transporter (DAT) is the primary mechanism of
      terminating dopamine signaling within the brain, thus playing an essential role
      in neuronal homeostasis. Deregulation of DAT function has been linked to several
      neurological and psychiatric disorders including ADHD, schizophrenia, Parkinson's
      disease, and drug addiction. Over the last 15 years, several studies have
      revealed a plethora of mechanisms influencing the activity and cellular
      distribution of DAT; suggesting that fine-tuning of dopamine homeostasis occurs
      via an elaborate interplay of multiple pathways. Here, we show for the first time
      that the betagamma subunits of G proteins regulate DAT activity. In heterologous
      cells and brain tissue, a physical association between Gbetagamma subunits and
      DAT was demonstrated by co-immunoprecipitation. Furthermore, in vitro pull-down
      assays using purified proteins established that this association occurs via a
      direct interaction between the intracellular carboxy-terminus of DAT and
      Gbetagamma. Functional assays performed in the presence of the non-hydrolyzable
      GTP analog GTP-gamma-S, Gbetagamma subunit overexpression, or the Gbetagamma
      activator mSIRK all resulted in rapid inhibition of DAT activity in heterologous
      systems. Gbetagamma activation by mSIRK also inhibited dopamine uptake in brain
      synaptosomes and dopamine clearance from mouse striatum as measured by high-speed
      chronoamperometry in vivo. Gbetagamma subunits are intracellular signaling
      molecules that regulate a multitude of physiological processes through
      interactions with enzymes and ion channels. Our findings add neurotransmitter
      transporters to the growing list of molecules regulated by G-proteins and suggest
      a novel role for Gbetagamma signaling in the control of dopamine homeostasis.

PMID- 23555782
TI  - JAK2 V617F genotype is a strong determinant of blast transformation in primary
      myelofibrosis.
AB  - PURPOSE: The influence of JAK2 V617F mutation on blast transformation (BT) and
      overall survival (OS) in primary myelofibrosis (PMF) is controversial. In a large
      cohort of patients we applied competing risks analysis for studying the influence
      of JAK2V617F mutation on BT in PMF. PATIENTS AND METHODS: In 462 PMF-fibrotic
      type patients (bone marrow [BM] fibrosis grade >0) we computed the incidence of
      BT and death in the framework of Cox regression analysis and of Fine and Gray
      competing risks analysis for BT. RESULTS: At the Cox regression analysis, having
      either a wild-type (wt) or a homozygous JAK2V617F genotype were factors for BT
      (HR, 1.98 and 2.04, respectively, with respect to the heterozygous genotype), but
      not for OS. At the competing risks regression analysis, the risk for BT in wt and
      homozygous V617F patients increased with respect to Cox analysis, giving a sHR of
      2.17 and 2.12, respectively. Correcting the results for the variables that could
      have influence on BT, JAK2V617F wt and homozygous genotypes remained
      independently associated with BT. In a validation cohort of 133 independent cases
      with PMF-prefibrotic type (BM fibrosis grade = 0), the BT predictive model
      including JAK2V617F genotype and older age retained high discriminant capacity (C
      statistics, 0.70; 95% CI, 0.47 to 0.92). CONCLUSION: The accumulation of mutated
      alleles in the JAK2V617F clone or the selective acquisition of a proliferative
      advantage in the wt clone are two relevant routes to BT in PMF. The influence of
      these results on treatment decisions with anti-JAK2 agents should be tested.

PMID- 23555783
TI  - Dynamic motile T cells highly respond to the T cell stimulation via PI3K-Akt and
      NF-kappaB pathways.
AB  - T lymphocytes (T cells) circulate from the blood into secondary lymphoid organs
      for immune surveillance. In this study, we hypothesized that circulating T cells
      are heterogeneous and can be grouped according to their differential migratory
      capacity in response to chemoattractants, rather than expressions of certain
      receptors or cytokines. We further hypothesized that, at least in part, this
      intrinsic difference in motility may be related to the T cell function. We
      established motile (m-T) and non-motile T (nm-T) cell lines based on their
      response to the chemokine SDF-1alpha. m-T cells showed more irregular and
      polarized morphologies than nm-T cells did. Interestingly, m-T cells produced
      higher levels of IL-2, a marker for T cell activation, than nm-T cells did after
      stimulation; however, no differences were observed in terms of surface expression
      of T cell receptors (TCR), adhesion molecules LFA-1 and ICAM-1, and chemokine
      receptor CXCR4. Both cell lines also showed similar membrane events (i.e., T cell
      APC conjugation, LFA-1 accumulation at the immunological synapse, and TCR
      internalization). In contrast, PKC-theta, a downstream of PI3K-Akt pathway was
      constitutively activated in m-T cells and the activation was more prominent
      during T cell stimulation. Consequently, NF-kappaB activity was selectively
      upregulated in m-T cells. This study is the first, to our knowledge, to
      demonstrate that T cells can be subcategorized on the basis of their intrinsic
      migratory capacity in relation to T cell activation.

PMID- 23555784
TI  - Berberine ameliorates chronic kidney injury caused by atherosclerotic
      renovascular disease through the suppression of NFkappaB signaling pathway in
      rats.
AB  - BACKGROUND AND OBJECTIVES: Impaired renal function in atherosclerotic
      renovascular disease (ARD) may be the result of crosstalk between atherosclerotic
      renovascular stenosis and amplified oxidative stress, inflammation and fibrosis.
      Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects.
      Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney
      injury through its cholesterol-lowering effect and also suppression of the
      pathways involved in oxidative stress, inflammation and NFkappaB activation.
      METHODS: Male rats were subjected to unilateral renal artery stenosis with silver
      irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with
      renal artery stenosis were randomly assigned to two groups (n = 6 each) - ARD, or
      ARD+BBR - according to diet alone or in combination with BBR. Similarly, age
      matched rats underwent sham operation and were also fed with hypercholesterolemic
      diet alone or in combination with BBR as two corresponding controls. Single
      kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to
      determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative
      stress, renal structure and function, inflammation and NFkappaB activation were
      measured, respectively. RESULTS: Compared with control rats, ARD rats had a
      significant increase in urinary albumin, plasma cholesterol, LDL and
      thiobarbituric acid reactive substances (TBARS) and a significant decrease in SOD
      activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in
      blood pressure, LDL, urinary albumin, and TBARS. In addition, there were
      significantly lower expression levels of iNOS and TGF-beta in the ARD+BBR group
      than in the ARD group, with attenuated NFkappaB-DNA binding activity and down
      regulated protein levels of subunits p65 and p50 as well as IKKbeta. CONCLUSIONS:
      We conclude that BBR can improve hypercholesterolemia and redox status in the
      kidney, eventually ameliorating chronic renal injury in rats with ARD, and that
      BBR can act against proinflammatory and profibrotic responses through suppression
      of the NFkappaB signaling pathway.

PMID- 23555785
TI  - 2,2'-diphenyl-3,3'-diindolylmethane: a potent compound induces apoptosis in
      breast cancer cells by inhibiting EGFR pathway.
AB  - Despite recent advances in medicine, 30-40% of patients with breast cancer show
      recurrence underscoring the need for improved effective therapy. In this study,
      by in vitro screening we have selected a novel synthetic indole derivative 2,2'
      diphenyl-3,3'-diindolylmethane (DPDIM) as a potential anti- breast cancer agent.
      DPDIM induces apoptosis both in vitro in breast cancer cells MCF7, MDA-MB 231 and
      MDA-MB 468 and in vivo in 7,12-dimethylbenz[alpha]anthracene (DMBA) induced
      Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show that DPDIM
      exerts apoptotic effect by negatively regulating the activity of EGFR and its
      downstream molecules like STAT3, AKT and ERK1/2 which are involved in the
      proliferation and survival of these cancer cells. In silico predictions also
      suggest that DPDIM may bind to EGFR at its ATP binding site. DPDIM furthermore
      inhibits EGF induced increased cell viability. We have also shown decreased
      expression of pro-survival factor Bcl-XL as well as increase in the level of pro
      apoptotic proteins like Bax, Bad, Bim in DPDIM treated cells in vitro and in
      vivo. Our results further indicate that the DPDIM induced apoptosis is mediated
      through mitochondrial apoptotic pathway involving the caspase-cascade. To the
      best of our knowledge this is the first report of DPDIM for its anticancer
      activity. Altogether this report suggests that DPDIM could be an effective
      therapeutic agent for breast cancer.

PMID- 23555786
TI  - Truncated cotton subtilase promoter directs guard cell-specific expression of
      foreign genes in tobacco and Arabidopsis.
AB  - A 993-bp regulatory region upstream of the translation start codon of subtilisin
      like serine protease gene was isolated from Gossypium barbadense. This (T/A)AAAG
      rich region, GbSLSP, and its 5'- and 3'-truncated versions were transferred into
      tobacco and Arabidopsis after fusing with GUS or GFP. Histochemical and
      quantitative GUS analysis and confocal GFP fluorescence scanning in the
      transgenic plants showed that the GbSLSP-driven GUS and GFP expressed
      preferentially in guard cells, whereas driven by GbSLSPF2 to GbSLSPF4, the 5'
      truncated GbSLSP versions with progressively reduced Dof1 elements, both GUS and
      GFP expressed exclusively in guard cells, and the expression strength declined
      with (T/A)AAAG copy decrement. Deletion of 5'-untranslated region from GbSLSP
      markedly weakened the activity of GUS and GFP, while deletion from the strongest
      guard cell-specific promoter, GbSLSPF2, not only significantly decreased the
      expression strength, but also completely abolished the guard cell specificity.
      These results suggested both guard cell specificity and expression strength of
      the promoters be coordinately controlled by 5'-untranslated region and a cluster
      of at least 3 (T/A)AAAG elements within a region of about 100 bp relative to
      transcription start site. Our guard cell-specific promoters will enrich tools to
      manipulate gene expression in guard cells for scientific research and crop
      improvement.

PMID- 23555787
TI  - In vitro dose-dependent inhibition of the intracellular spontaneous calcium
      oscillations in developing hippocampal neurons by ketamine.
AB  - Spatial and temporal abnormalities in the frequency and amplitude of the
      cytosolic calcium oscillations can impact the normal physiological functions of
      neuronal cells. Recent studies have shown that ketamine can affect the growth and
      development and even induce the apoptotic death of neurons. This study used
      isolated developing hippocampal neurons as its study subjects to observe the
      effect of ketamine on the intracellular calcium oscillations in developing
      hippocampal neurons and to further explore its underlying mechanism using Fluo-4
      loaded laser scanning confocal microscopy. Using a semi-quantitative method to
      analyze the spontaneous calcium oscillatory activities, a typical type of calcium
      oscillation was observed in developing hippocampal neurons. In addition, the
      administration of NMDA (N-Methyl-D-aspartate) at a concentration of 100 uM
      increased the calcium oscillation amplitude. The administration of MK801 at a
      concentration of 40 uM inhibited the amplitude and frequency of the calcium
      oscillations. Our results demonstrated that an increase in the ketamine
      concentration, starting from 30 uM, gradually decreased the neuronal calcium
      oscillation amplitude. The inhibition of the calcium oscillation frequency by 300
      uM ketamine was statistically significant, and the neuronal calcium oscillations
      were completely eliminated with the administration of 3,000 uM Ketamine. The
      administration of 100, 300, and 1,000 uM NMDA to the 1 mM ketamine-pretreated
      hippocampal neurons restored the frequency and amplitude of the calcium
      oscillations in a dose-dependent manner. In fact, a concentration of 1,000 uM
      NMDA completely reversed the decrease in the calcium oscillation frequency and
      amplitude that was induced by 1 mM ketamine. This study revealed that ketamine
      can inhibit the frequency and amplitude of the calcium oscillations in developing
      hippocampal neurons though the NMDAR (NMDA receptor) in a dose-dependent manner,
      which might highlight a possible underlying mechanism of ketamine toxicity on the
      rat hippocampal neurons during development.

PMID- 23555788
TI  - Marked increase in PROP taste responsiveness following oral supplementation with
      selected salivary proteins or their related free amino acids.
AB  - The genetic predisposition to taste 6-n-propylthiouracil (PROP) varies among
      individuals and is associated with salivary levels of Ps-1 and II-2 peptides,
      belonging to the basic proline-rich protein family (bPRP). We evaluated the role
      of these proteins and free amino acids that selectively interact with the PROP
      molecule, in modulating bitter taste responsiveness. Subjects were classified by
      their PROP taster status based on ratings of perceived taste intensity for PROP
      and NaCl solutions. Quantitative and qualitative determinations of Ps-1 and II-2
      proteins in unstimulated saliva were performed by HPLC-ESI-MS analysis. Subjects
      rated PROP bitterness after supplementation with Ps-1 and II-2, and two amino
      acids (L-Arg and L-Lys) whose interaction with PROP was demonstrated by (1)H-NMR
      spectroscopy. ANOVA showed that salivary levels of II-2 and Ps-1 proteins were
      higher in unstimulated saliva of PROP super-tasters and medium tasters than in
      non-tasters. Supplementation of Ps-1 protein in individuals lacking it in saliva
      enhanced their PROP bitter taste responsiveness, and this effect was specific to
      the non-taster group.(1)H-NMR results showed that the interaction between PROP
      and L-Arg is stronger than that involving L-Lys, and taste experiments confirmed
      that oral supplementation with these two amino acids increased PROP bitterness
      intensity, more for L-Arg than for L-Lys. These data suggest that Ps-1 protein
      facilitates PROP bitter taste perception and identifies a role for free L-Arg and
      L-Lys in PROP tasting.

PMID- 23555789
TI  - Development of the mouse dermal adipose layer occurs independently of
      subcutaneous adipose tissue and is marked by restricted early expression of
      FABP4.
AB  - The laboratory mouse is a key animal model for studies of adipose biology,
      metabolism and disease, yet the developmental changes that occur in tissues and
      cells that become the adipose layer in mouse skin have received little attention.
      Moreover, the terminology around this adipose body is often confusing, as
      frequently no distinction is made between adipose tissue within the skin, and so
      called subcutaneous fat. Here adipocyte development in mouse dorsal skin was
      investigated from before birth to the end of the first hair follicle growth
      cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and
      TUNEL staining we confirmed previous observations of a close spatio-temporal link
      between hair follicle development and the process of adipogenesis. However,
      unlike previous studies, we observed that the skin adipose layer was created from
      cells within the lower dermis. By day 16 of embryonic development (e16) the lower
      dermis was demarcated from the upper dermal layer, and commitment to adipogenesis
      in the lower dermis was signalled by expression of FABP4, a marker of adipocyte
      differentiation. In mature mice the skin adipose layer is separated from
      underlying subcutaneous adipose tissue by the panniculus carnosus. We observed
      that the skin adipose tissue did not combine or intermix with subcutaneous
      adipose tissue at any developmental time point. By transplanting skin isolated
      from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of
      adult mice, we showed that skin adipose tissue develops independently and without
      influence from subcutaneous depots. This study has reinforced the developmental
      link between hair follicles and skin adipocyte biology. We argue that because
      skin adipocytes develop from cells within the dermis and independently from
      subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue
      and that, in laboratory mice at least, it represents a separate adipose depot.

PMID- 23555790
TI  - Specific in vivo labeling of tyrosinated alpha-tubulin and measurement of
      microtubule dynamics using a GFP tagged, cytoplasmically expressed recombinant
      antibody.
AB  - GFP-tagged proteins are used extensively as biosensors for protein localization
      and function, but the GFP moiety can interfere with protein properties. An
      alternative is to indirectly label proteins using intracellular recombinant
      antibodies (scFvs), but most antibody fragments are insoluble in the reducing
      environment of the cytosol. From a synthetic hyperstable human scFv library we
      isolated an anti-tubulin scFv, 2G4, which is soluble in mammalian cells when
      expressed as a GFP-fusion protein. Here we report the use of this GFP-tagged scFv
      to label microtubules in fixed and living cells. We found that 2G4-GFP localized
      uniformly along microtubules and did not disrupt binding of EB1, a protein that
      binds microtubule ends and serves as a platform for binding by a complex of
      proteins regulating MT polymerization. TOGp and CLIP-170 also bound microtubule
      ends in cells expressing 2G4-GFP. Microtubule dynamic instability, measured by
      tracking 2G4-GFP labeled microtubules, was nearly identical to that measured in
      cells expressing GFP-alpha-tubulin. Fluorescence recovery after photobleaching
      demonstrated that 2G4-GFP turns over rapidly on microtubules, similar to the
      turnover rates of fluorescently tagged microtubule-associated proteins. These
      data indicate that 2G4-GFP binds relatively weakly to microtubules, and this
      conclusion was confirmed in vitro. Purified 2G4 partially co-pelleted with
      microtubules, but a significant fraction remained in the soluble fraction, while
      a second anti-tubulin scFv, 2F12, was almost completely co-pelleted with
      microtubules. In cells, 2G4-GFP localized to most microtubules, but did not co
      localize with those composed of detyrosinated alpha-tubulin, a post-translational
      modification associated with non-dynamic, more stable microtubules. Immunoblots
      probing bacterially expressed tubulins confirmed that 2G4 recognized alpha
      tubulin and required tubulin's C-terminal tyrosine residue for binding. Thus, a
      recombinant antibody with weak affinity for its substrate can be used as a
      specific intracellular biosensor that can differentiate between unmodified and
      post-translationally modified forms of a protein.

PMID- 23555791
TI  - Descriptive epidemiology and underlying psychiatric disorders among
      hospitalizations with self-directed violence.
AB  - BACKGROUND: Suicide claims over one million lives worldwide each year. In the
      United States, 1 per 10,000 persons dies from suicide every year, and these rates
      have remained relatively constant over the last 20 years. There are nearly 25
      suicide attempts for each suicide, and previous self-directed violence is a
      strong predictor of death from suicide. While many studies have focused on
      suicides, the epidemiology of non-fatal self-directed violence is not well
      defined. OBJECTIVE: We used a nationally representative survey to examine
      demographics and underlying psychiatric disorders in United States (US)
      hospitalizations with non-fatal self-directed violence (SDV). METHOD:
      International Classification of Disease, 9(th) Revision (ICD-9) discharge
      diagnosis data from the National Hospital Discharge Survey (NHDS) were examined
      from 1997 to 2006 using frequency measures and adjusted logistic regression.
      RESULTS: The rate of discharges with SDV remained relatively stable over the
      study time period with 4.5 to 5.7 hospitalizations per 10,000 persons per year.
      Excess SDV was documented for females, adolescents, whites, and those from the
      Midwest or West. While females had a higher likelihood of self-poisoning, both
      genders had comparable proportions of hospitalizations with SDV resulting in
      injury. Over 86% of the records listing SDV also included psychiatric disorders,
      with the most frequent being affective (57.8%) and substance abuse (37.1%)
      disorders. The association between psychiatric disorders and self-injury was
      strongest for personality disorders for both males (OR = 2.1; 95% CI = 1.3-3.4)
      and females (OR = 3.8; 95% CI = 2.7-5.3). CONCLUSION: The NHDS provides new
      insights into the demographics and psychiatric morbidity of those hospitalized
      with SDV. Classification of SDV as self-injury or self-poisoning provides an
      additional parameter useful to epidemiologic studies.

PMID- 23555792
TI  - Characterization of a single-chain variable fragment recognizing a linear epitope
      of abeta: a biotechnical tool for studies on Alzheimer's disease?
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with
      devastating effects. Currently, therapeutic options are limited to symptomatic
      treatment. For more than a decade, research focused on immunotherapy for the
      causal treatment of AD. However, clinical trials with active immunization using
      Abeta encountered severe complications, for example meningoencephalitis.
      Consequently, attention focused on passive immunization using antibodies. As an
      alternative to large immunoglobulins (IgGs), Abeta binding single-chain variable
      fragments (scFvs) were used for diagnostic and therapeutic research approaches.
      scFvs can be expressed in E. coli and may provide improved pharmacokinetic
      properties like increased blood-brain barrier permeability or reduced side
      effects in vivo. In this study, we constructed an scFv from an Abeta binding IgG,
      designated IC16, which binds the N-terminal region of Abeta (Abeta(1-8)). scFv
      IC16 was expressed in E. coli, purified and characterized with respect to its
      interaction with different Abeta species and its influence on Abeta fibril
      formation. We were able to show that scFv-IC16 strongly influenced the
      aggregation behavior of Abeta and could be applied as an Abeta detection probe
      for plaque staining in the brains of transgenic AD model mice. The results
      indicate potential for therapy and diagnosis of AD.

PMID- 23555793
TI  - The golgin tether giantin regulates the secretory pathway by controlling stack
      organization within Golgi apparatus.
AB  - Golgins are coiled-coil proteins that play a key role in the regulation of Golgi
      architecture and function. Giantin, the largest golgin in mammals, forms a
      complex with p115, rab1, GM130, and soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNAREs), thereby facilitating vesicle tethering and
      fusion processes around the Golgi apparatus. Treatment with the microtubule
      destabilizing drug nocodazole transforms the Golgi ribbon into individual Golgi
      stacks. Here we show that siRNA-mediated depletion of giantin resulted in more
      dispersed Golgi stacks after nocodazole treatment than by control treatment,
      without changing the average cisternal length. Furthermore, depletion of giantin
      caused an increase in cargo transport that was associated with altered cell
      surface protein glycosylation. Drosophila S2 cells are known to have dispersed
      Golgi stacks and no giantin homolog. The exogenous expression of mammalian
      giantin cDNA in S2 cells resulted in clustered Golgi stacks, similar to the Golgi
      ribbon in mammalian cells. These results suggest that the spatial organization of
      the Golgi ribbon is mediated by giantin, which also plays a role in cargo
      transport and sugar modifications.

PMID- 23555794
TI  - Direct and indirect effects of climate on demography and early growth of Pinus
      sylvestris at the rear edge: changing roles of biotic and abiotic factors.
AB  - Global change triggers shifts in forest composition, with warming and
      aridification being particularly threatening for the populations located at the
      rear edge of the species distributions. This is the case of Scots pine (Pinus
      sylvestris) in the Mediterranean Basin where uncertainties in relation to its
      dynamics under these changing scenarios are still high. We analysed the relative
      effect of climate on the recruitment patterns of Scots pine and its interactions
      with local biotic and abiotic variables at different spatial scales. Number of
      seedlings and saplings was surveyed, and their annual shoot growth measured in 96
      plots located across altitudinal gradients in three different regions in the
      Iberian Peninsula. We found a significant influence of climate on demography and
      performance of recruits, with a non-linear effect of temperature on the presence
      of juveniles, and a positive effect of precipitation on their survival. Abundance
      of juveniles of P. sylvestris that underwent their first summer drought was
      skewed towards higher altitudes than the altitudinal mean range of the
      conspecific adults and the optimum elevation for seedlings' emergence. At local
      level, light availability did not influence juveniles' density, but it enhanced
      their growth. Biotic interactions were found between juveniles and the herb cover
      (competition) and between the number of newly emerged seedlings and shrubs
      (facilitation). Results also highlighted the indirect effect that climate exerts
      over the local factors, modulating the interactions with the pre-existing
      vegetation that were more evident at more stressful sites. This multiscale
      approach improves our understanding of the dynamics of these marginal populations
      and some management criteria can be inferred to boost their conservation under
      the current global warming.

PMID- 23555795
TI  - Ovariectomy induces a shift in fuel availability and metabolism in the
      hippocampus of the female transgenic model of familial Alzheimer's.
AB  - Previously, we demonstrated that reproductive senescence in female triple
      transgenic Alzheimer's (3*TgAD) mice was paralleled by a shift towards a
      ketogenic profile with a concomitant decline in mitochondrial activity in brain,
      suggesting a potential association between ovarian hormone loss and alteration in
      the bioenergetic profile of the brain. In the present study, we investigated the
      impact of ovariectomy and 17beta-estradiol replacement on brain energy substrate
      availability and metabolism in a mouse model of familial Alzheimer's (3*TgAD).
      Results of these analyses indicated that ovarian hormones deprivation by
      ovariectomy (OVX) induced a significant decrease in brain glucose uptake
      indicated by decline in 2-[(18)F]fluoro-2-deoxy-D-glucose uptake measured by
      microPET-imaging. Mechanistically, OVX induced a significant decline in blood
      brain-barrier specific glucose transporter expression, hexokinase expression and
      activity. The decline in glucose availability was accompanied by a significant
      rise in glial LDH5 expression and LDH5/LDH1 ratio indicative of lactate
      generation and utilization. In parallel, a significant rise in ketone body
      concentration in serum occurred which was coupled to an increase in neuronal MCT2
      expression and 3-oxoacid-CoA transferase (SCOT) required for conversion of ketone
      bodies to acetyl-CoA. In addition, OVX-induced decline in glucose metabolism was
      paralleled by a significant increase in Abeta oligomer levels. 17beta-estradiol
      preserved brain glucose-driven metabolic capacity and partially prevented the OVX
      induced shift in bioenergetic substrate as evidenced by glucose uptake, glucose
      transporter expression and gene expression associated with aerobic glycolysis.
      17beta-estradiol also partially prevented the OVX-induced increase in Abeta
      oligomer levels. Collectively, these data indicate that ovarian hormone loss in a
      preclinical model of Alzheimer's was paralleled by a shift towards the metabolic
      pathway required for metabolism of alternative fuels in brain with a concomitant
      decline in brain glucose transport and metabolism. These findings also indicate
      that estrogen plays a critical role in sustaining brain bioenergetic capacity
      through preservation of glucose metabolism.

PMID- 23555796
TI  - Early warning scores generated in developed healthcare settings are not
      sufficient at predicting early mortality in Blantyre, Malawi: a prospective
      cohort study.
AB  - AIM: Early warning scores (EWS) are widely used in well-resourced healthcare
      settings to identify patients at risk of mortality. The Modified Early Warning
      Score (MEWS) is a well-known EWS used comprehensively in the United Kingdom. The
      HOTEL score (Hypotension, Oxygen saturation, Temperature, ECG abnormality, Loss
      of independence) was developed and tested in a European cohort; however, its
      validity is unknown in resource limited settings. This study compared the
      performance of both scores and suggested modifications to enhance accuracy.
      METHODS: A prospective cohort study of adults (>=18 yrs) admitted to medical
      wards at a Malawian hospital. Primary outcome was mortality within three days.
      Performance of MEWS and HOTEL were assessed using ROC analysis. Logistic
      regression analysis identified important predictors of mortality and from this a
      new score was defined. RESULTS: Three-hundred-and-two patients were included.
      Fifty-one (16.9%) died within three days of admission. With a cut-point >=2, the
      HOTEL score had sensitivity 70.6% (95% CI: 56.2 to 82.5) and specificity 59.4%
      (95% CI: 53.0 to 65.5), and was superior to MEWS (cut-point >=5); sensitivity:
      58.8% (95% CI: 44.2 to 72.4), specificity: 56.2% (95% CI: 49.8 to 62.4). The new
      score, dubbed TOTAL (Tachypnoea, Oxygen saturation, Temperature, Alert, Loss of
      independence), showed slight improvement with a cut-point >=2; sensitivity 76.5%
      (95% CI: 62.5 to 87.2) and specificity 67.3% (95% CI: 61.1 to 73.1). CONCLUSION:
      Using an EWS generated in developed healthcare systems in resource limited
      settings results in loss of sensitivity and specificity. A score based on
      predictors of mortality specific to the Malawian population showed enhanced
      accuracy but not enough to warrant clinical use. Despite an assumption of common
      physiological responses, disease and population differences seem to strongly
      determine the performance of EWS. Local validation and impact assessment of these
      scores should precede their adoption in resource limited settings.

PMID- 23555797
TI  - Side effects of being blue: influence of sad mood on visual statistical learning.
AB  - It is well established that mood influences many cognitive processes, such as
      learning and executive functions. Although statistical learning is assumed to be
      part of our daily life, as mood does, the influence of mood on statistical
      learning has never been investigated before. In the present study, a sad vs.
      neutral mood was induced to the participants through the listening of stories
      while they were exposed to a stream of visual shapes made up of the repeated
      presentation of four triplets, namely sequences of three shapes presented in a
      fixed order. Given that the inter-stimulus interval was held constant within and
      between triplets, the only cues available for triplet segmentation were the
      transitional probabilities between shapes. Direct and indirect measures of
      learning taken either immediately or 20 minutes after the exposure/mood induction
      phase revealed that participants learned the statistical regularities between
      shapes. Interestingly, although participants from the sad and neutral groups
      performed similarly in these tasks, subjective measures (confidence judgments
      taken after each trial) revealed that participants who experienced the sad mood
      induction showed increased conscious access to their statistical knowledge. These
      effects were not modulated by the time delay between the exposure/mood induction
      and the test phases. These results are discussed within the scope of the
      robustness principle and the influence of negative affects on processing style.

PMID- 23555798
TI  - Clustering and alignment of polymorphic sequences for HLA-DRB1 genotyping.
AB  - Located on Chromosome 6p21, classical human leukocyte antigen genes are highly
      polymorphic. HLA alleles associate with a variety of phenotypes, such as
      narcolepsy, autoimmunity, as well as immunologic response to infectious disease.
      Moreover, high resolution genotyping of these loci is critical to achieving long
      term survival of allogeneic transplants. Development of methods to obtain high
      resolution analysis of HLA genotypes will lead to improved understanding of how
      select alleles contribute to human health and disease risk. Genomic DNAs were
      obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative
      Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using
      sequence specific oligonucleotide probes and by next-generation sequencing using
      the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic
      Sequences (CAPSeq) software application was developed to analyze next-generation
      sequencing data. The application generates HLA sequence specific 6-digit genotype
      information from next-generation sequencing data using MUMmer to align sequences
      and the R package diffusionMap to classify sequences into their respective
      allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in
      sorting of sequences into allele classes resulted in improved genotyping
      accuracy. Using Bagging iterations equal to 60, the genotyping results obtained
      using CAPSeq when compared with sequence specific oligonucleotide probe
      characterized 4-digit genotypes exhibited high rates of concordance, matching at
      759 out of 766 (99.1%) alleles.

PMID- 23555799
TI  - Theoretical analysis of the local field potential in deep brain stimulation
      applications.
AB  - Deep brain stimulation (DBS) is a common therapy for treating movement disorders,
      such as Parkinson's disease (PD), and provides a unique opportunity to study the
      neural activity of various subcortical structures in human patients. Local field
      potential (LFP) recordings are often performed with either intraoperative
      microelectrodes or DBS leads and reflect oscillatory activity within nuclei of
      the basal ganglia. These LFP recordings have numerous clinical implications and
      might someday be used to optimize DBS outcomes in closed-loop systems. However,
      the origin of the recorded LFP is poorly understood. Therefore, the goal of this
      study was to theoretically analyze LFP recordings within the context of clinical
      DBS applications. This goal was achieved with a detailed recording model of beta
      oscillations (~20 Hz) in the subthalamic nucleus. The recording model consisted
      of finite element models of intraoperative microelectrodes and DBS
      macroelectrodes implanted in the brain along with multi-compartment cable models
      of STN projection neurons. Model analysis permitted systematic investigation into
      a number of variables that can affect the composition of the recorded LFP (e.g.
      electrode size, electrode impedance, recording configuration, and filtering
      effects of the brain, electrode-electrolyte interface, and recording
      electronics). The results of the study suggest that the spatial reach of the LFP
      can extend several millimeters. Model analysis also showed that variables such as
      electrode geometry and recording configuration can have a significant effect on
      LFP amplitude and spatial reach, while the effects of other variables, such as
      electrode impedance, are often negligible. The results of this study provide
      insight into the origin of the LFP and identify variables that need to be
      considered when analyzing LFP recordings in clinical DBS applications.

PMID- 23555800
TI  - Haptoglobin preferentially binds beta but not alpha subunits cross-linked
      hemoglobin tetramers with minimal effects on ligand and redox reactions.
AB  - Human hemoglobin (Hb) and haptoglobin (Hp) exhibit an extremely high affinity for
      each other, and the dissociation of Hb tetramers into dimers is generally
      believed to be a prerequisite for complex formation. We have investigated Hp
      interactions with native Hb, alphaalpha, and betabeta cross-linked Hb
      (alphaalphaXLHb and betabetaXLHb, respectively), and rapid kinetics of Hb ligand
      binding as well as the redox reactivity in the presence of and absence of Hp. The
      quaternary conformation of betabeta subunit cross-linking results in a higher
      binding affinity than that of alphaalpha subunit cross-linked Hb. However,
      betabeta cross-linked Hb exhibits a four fold slower association rate constant
      than the reaction rate of unmodified Hb with Hp. The Hp contact regions in the Hb
      dimer interfaces appear to be more readily exposed in betabetaXLHb than
      alphaalphaXLHb. In addition, apart from the functional changes caused by chemical
      modifications, Hp binding does not induce appreciable effects on the ligand
      binding and redox reactions of betabetaXLHb. Our findings may therefore be
      relevant to the design of safer Hb-based oxygen therapeutics by utilizing this
      preferential binding of betabetaXLHb to Hp. This may ultimately provide a safe
      oxidative inactivation and clearance pathway for chemically modified Hbs in
      circulation.

PMID- 23555801
TI  - BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling.
AB  - The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid
      tyrosine kinase (BLK) have been genetically associated with autoimmunity. The
      proteins of these genes interact physically and work in concert during B-cell
      signaling. Little is know about their interactions with other B-cell signaling
      molecules or their role in the process. Using yeast two hybrid (Y2H) we sought
      for factors that interact with BANK1. We found that the molecular switch PLCg2
      interacts with BANK1 and that the interaction is promoted by B-cell receptor
      (BCR) stimulation. We found further that the kinase activity of BLK enhanced
      BANK1- PLCg2 binding and that the interaction was suppressed upon BLK depletion.
      Immunoprecipitation and mutational analysis demonstrated that the interaction
      between BANK1 and PLCg2 was dependent on specific tyrosine and proline residues
      on the adaptor protein. Our results provide new information important to
      understand the role of these two genes in basic B-cell physiology and immune
      related diseases.

PMID- 23555802
TI  - Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2
      pathway.
AB  - Oxidative damage plays a critical role in many diseases of the central nervous
      system. This study was conducted to determine the molecular mechanisms involved
      in the putative anti-oxidative effects of curcumin against experimental stroke.
      Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic
      insult in primary cultured cortical neurons. A rapid increase in the
      intracellular expression of NAD(P)H: quinone oxidoreductase1 (NQO1) induced by
      OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell
      injury. The reduction of phosphorylation Akt induced by OGD was restored by
      curcumin. Consequently, NQO1 expression and the binding activity of nuclear
      factor-erythroid 2-related factor 2 (Nrf2) to antioxidant response element (ARE)
      were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin
      and abolished the associated protective effect. Adult male Sprague-Dawley rats
      were subjected to transient middle cerebral artery occlusion for 60 minutes.
      Curcumin administration significantly reduced infarct size. Curcumin also
      markedly reduced oxidative stress levels in middle cerebral artery occlusion
      (MCAO) rats; hence, these effects were all suppressed by LY294002. Taken
      together, these findings provide evidence that curcumin protects neurons against
      ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway.
      In addition, Nrf2 is involved in the neuroprotective effects of curcumin against
      oxidative damage.

PMID- 23555803
TI  - The CouPSTU and TarPQM transporters in Rhodopseudomonas palustris: redundant,
      promiscuous uptake systems for lignin-derived aromatic substrates.
AB  - The biodegradation of lignin, one of the most abundant carbon compounds on Earth,
      has important biotechnological applications in the derivation of useful products
      from lignocellulosic wastes. The purple photosynthetic bacterium Rhodopseudomonas
      palustris is able to grow photoheterotrophically under anaerobic conditions on a
      range of phenylpropeneoid lignin monomers, including coumarate, ferulate,
      caffeate, and cinnamate. RPA1789 (CouP) is the periplasmic binding-protein
      component of an ABC system (CouPSTU; RPA1789, RPA1791-1793), which has previously
      been implicated in the active transport of this class of aromatic substrate.
      Here, we show using both intrinsic tryptophan fluorescence and isothermal
      titration calorimetry that CouP binds a range of phenylpropeneoid ligands with K
      d values in the nanomolar range. The crystal structure of CouP with ferulate as
      the bound ligand shows H-bond interactions between the 4-OH group of the aromatic
      ring with His309 and Gln305. H-bonds are also made between the carboxyl group on
      the ferulate side chain and Arg197, Ser222, and Thr102. An additional transport
      system (TarPQM; RPA1782-1784), a member of the tripartite ATP-independent
      periplasmic (TRAP) transporter family, is encoded at the same locus as rpa1789
      and several other genes involved in coumarate metabolism. We show that the
      periplasmic binding-protein of this system (TarP; RPA1782) also binds coumarate,
      ferulate, caffeate, and cinnamate with nanomolar K d values. Thus, we conclude
      that R. palustris uses two redundant but energetically distinct primary and
      secondary transporters that both employ high-affinity periplasmic binding
      proteins to maximise the uptake of lignin-derived aromatic substrates from the
      environment. Our data provide a detailed thermodynamic and structural basis for
      understanding the interaction of lignin-derived aromatic substrates with proteins
      and will be of use in the further exploitation of the flexible metabolism of R.
      palustris for anaerobic aromatic biotransformations.

PMID- 23555804
TI  - Do changes in the pace of events affect one-off judgments of duration?
AB  - Five experiments examined whether changes in the pace of external events
      influence people's judgments of duration. In Experiments 1a-1c, participants
      heard pieces of music whose tempo accelerated, decelerated, or remained constant.
      In Experiment 2, participants completed a visuo-motor task in which the rate of
      stimulus presentation accelerated, decelerated, or remained constant. In
      Experiment 3, participants completed a reading task in which facts appeared on
      screen at accelerating, decelerating, or constant rates. In all experiments, the
      physical duration of the to-be-judged interval was the same across conditions. We
      found no significant effects of temporal structure on duration judgments in any
      of the experiments, either when participants knew that a time estimate would be
      required (prospective judgments) or when they did not (retrospective judgments).
      These results provide a starting point for the investigation of how temporal
      structure affects one-off judgments of duration like those typically made in
      natural settings.

PMID- 23555806
TI  - Computational discovery of transcriptional regulatory modules in fungal ribosome
      biogenesis genes reveals novel sequence and function patterns.
AB  - Genes involved in ribosome biogenesis and assembly (RBA) are responsible for
      ribosome formation. In Saccharomyces cerevisiae, their transcription is regulated
      by two dissimilar DNA motifs. We were interested in analyzing conservation and
      divergence of RBA transcription regulation machinery throughout fungal evolution.
      We have identified orthologs of S. cerevisiae RBA genes in 39 species across
      fungal phylogeny and searched upstream regions of these gene sets for DNA
      sequences significantly similar to S. cerevisiae RBA regulatory motifs. In
      addition to confirming known motif arrangements comprising two different motifs
      in a set of S. cerevisiae close relatives or two instances of the same motif
      (that we refer to as modules), we have also discovered novel modules in a group
      of fungi closely related to Neurospora crassa. Despite a single nucleotide
      difference between consensus sequences of RBA motifs, modules associated with S,
      cerevisiae group and N. crassa group displayed consistently different
      characteristics with respect to preferred module organization and several other
      module properties. For a given species, we have found a correlation between the
      configuration of the RBA module and significant enrichment in a set of specific
      Gene Ontology biological processes. We have identified several likely new
      candidates for a role in ribosome biogenesis in S. cerevisiae based on the
      combined evidence of RBA module presence in the upstream regions, functional
      annotation information and microarray expression profiles. We believe that this
      approach will be useful in terms of generating hypotheses about functional roles
      of genes for which only fragmentary data from a single source are available.

PMID- 23555805
TI  - Individual differences in fornix microstructure and body mass index.
AB  - The prevalence of obesity and associated health conditions is increasing in the
      developed world. Obesity is related to atrophy and dysfunction of the hippocampus
      and hippocampal lesions may lead to increased appetite and weight gain. The
      hippocampus is connected via the fornix tract to the hypothalamus, orbitofrontal
      cortex, and the nucleus accumbens, all key structures for homeostatic and reward
      related control of food intake. The present study employed diffusion MRI
      tractography to investigate the relationship between microstructural properties
      of the fornix and variation in Body Mass Index (BMI), within normal and
      overweight ranges, in a group of community-dwelling older adults (53-93 years
      old). Larger BMI was associated with larger axial and mean diffusivity in the
      fornix (r = 0.64 and r = 0.55 respectively), relationships that were most
      pronounced in overweight individuals. Moreover, controlling for age, education,
      cognitive performance, blood pressure and global brain volume increased these
      correlations. Similar associations were not found in the parahippocampal
      cingulum, a comparison temporal association pathway. Thus, microstructural
      changes in fornix white matter were observed in older adults with increasing BMI
      levels from within normal to overweight ranges, so are not exclusively related to
      obesity. We propose that hippocampal-hypothalamic-prefrontal interactions,
      mediated by the fornix, contribute to the healthy functioning of networks
      involved in food intake control. The fornix, in turn, may display alterations in
      microstructure that reflect weight gain.

PMID- 23555807
TI  - Automaticity and control in prospective memory: a computational model.
AB  - Prospective memory (PM) refers to our ability to realize delayed intentions. In
      event-based PM paradigms, participants must act on an intention when they detect
      the occurrence of a pre-established cue. Some theorists propose that in such
      paradigms PM responding can only occur when participants deliberately initiate
      processes for monitoring their environment for appropriate cues. Others propose
      that perceptual processing of PM cues can directly trigger PM responding in the
      absence of strategic monitoring, at least under some circumstances. In order to
      address this debate, we present a computational model implementing the latter
      account, using a parallel distributed processing (interactive activation)
      framework. In this model PM responses can be triggered directly as a result of
      spreading activation from units representing perceptual inputs. PM responding can
      also be promoted by top-down monitoring for PM targets. The model fits a wide
      variety of empirical findings from PM paradigms, including the effect of
      maintaining PM intentions on ongoing response time and the intention superiority
      effect. The model also makes novel predictions concerning the effect of stimulus
      degradation on PM performance, the shape of response time distributions on
      ongoing and prospective memory trials, and the effects of instructing
      participants to make PM responses instead of ongoing responses or alongside them.
      These predictions were confirmed in two empirical experiments. We therefore
      suggest that PM should be considered to result from the interplay between bottom
      up triggering of PM responses by perceptual input, and top-down monitoring for
      appropriate cues. We also show how the model can be extended to simulate encoding
      new intentions and subsequently deactivating them, and consider links between the
      model's performance and results from neuroimaging.

PMID- 23555808
TI  - Predicting environmental suitability for a rare and threatened species (Lao newt,
      Laotriton laoensis) using validated species distribution models.
AB  - The Lao newt (Laotriton laoensis) is a recently described species currently known
      only from northern Laos. Little is known about the species, but it is threatened
      as a result of overharvesting. We integrated field survey results with climate
      and altitude data to predict the geographic distribution of this species using
      the niche modeling program Maxent, and we validated these predictions by using
      interviews with local residents to confirm model predictions of presence and
      absence. The results of the validated Maxent models were then used to
      characterize the environmental conditions of areas predicted suitable for L.
      laoensis. Finally, we overlaid the resulting model with a map of current national
      protected areas in Laos to determine whether or not any land predicted to be
      suitable for this species is coincident with a national protected area. We found
      that both area under the curve (AUC) values and interview data provided strong
      support for the predictive power of these models, and we suggest that interview
      data could be used more widely in species distribution niche modeling. Our
      results further indicated that this species is mostly likely geographically
      restricted to high altitude regions (i.e., over 1,000 m elevation) in northern
      Laos and that only a minute fraction of suitable habitat is currently protected.
      This work thus emphasizes that increased protection efforts, including listing
      this species as endangered and the establishment of protected areas in the region
      predicted to be suitable for L. laoensis, are urgently needed.

PMID- 23555810
TI  - The onset of widespread musculoskeletal pain is associated with a decrease in
      healthy ageing in older people: a population-based prospective study.
AB  - OBJECTIVE: Chronic musculoskeletal pain is common in older adults but the nature
      of its relationship with ageing is unclear. The objective for this study was to
      test the hypothesis that the onset of widespread pain would be associated with a
      decrease in healthy ageing. METHODS: Population-based prospective cohort study. A
      "healthy ageing" index was constructed across biomedical, physical, psychosocial
      and lay components. Analysis was performed with 2949 adults aged 50 years and
      over who had complete index scores at baseline, 3 and 6-year follow-ups. RESULTS:
      At three and six year follow-up, 365 (16.8%) and 259 (14.3%) experienced the
      onset of widespread pain. The onset of widespread pain during the six-year period
      was associated with a 25% and a 46% decrease in healthy ageing index scores; this
      decrease was independent of age, sex, education, social networks, smoking status,
      alcohol consumption and physical inactivity. The decrease in healthy ageing
      attenuated to 20% and 39% following adjustment for diagnosed musculoskeletal
      conditions and analgesic and non-steroidal use. CONCLUSIONS: The onset of
      widespread pain was associated with a decrease in healthy ageing throughout the
      six-year period. When pain increased over time, the markers of unhealthy ageing
      increased also. Strong analgesia was associated with unhealthy ageing. Research
      could now usefully test whether early identification, improved treatment and
      prevention of pain prior to old age may facilitate healthy ageing.

PMID- 23555809
TI  - Song competition affects monoamine levels in sensory and motor forebrain regions
      of male Lincoln's sparrows (Melospiza lincolnii).
AB  - Male animals often change their behavior in response to the level of competition
      for mates. Male Lincoln's sparrows (Melospiza lincolnii) modulate their
      competitive singing over the period of a week as a function of the level of
      challenge associated with competitors' songs. Differences in song challenge and
      associated shifts in competitive state should be accompanied by neural changes,
      potentially in regions that regulate perception and song production. The
      monoamines mediate neural plasticity in response to environmental cues to achieve
      shifts in behavioral state. Therefore, using high pressure liquid chromatography
      with electrochemical detection, we compared levels of monoamines and their
      metabolites from male Lincoln's sparrows exposed to songs categorized as more or
      less challenging. We compared levels of norepinephrine and its principal
      metabolite in two perceptual regions of the auditory telencephalon, the
      caudomedial nidopallium and the caudomedial mesopallium (CMM), because this
      chemical is implicated in modulating auditory sensitivity to song. We also
      measured the levels of dopamine and its principal metabolite in two song control
      nuclei, area X and the robust nucleus of the arcopallium (RA), because dopamine
      is implicated in regulating song output. We measured the levels of serotonin and
      its principal metabolite in all four brain regions because this monoamine is
      implicated in perception and behavioral output and is found throughout the avian
      forebrain. After controlling for recent singing, we found that males exposed to
      more challenging song had higher levels of norepinephrine metabolite in the CMM
      and lower levels of serotonin in the RA. Collectively, these findings are
      consistent with norepinephrine in perceptual brain regions and serotonin in song
      control regions contributing to neuroplasticity that underlies socially-induced
      changes in behavioral state.

PMID- 23555811
TI  - Flow cytometric assessment of erythrocyte shape through analysis of FSC
      histograms: use of kurtosis and implications for longitudinal evaluation.
AB  - Sphericity of erythrocytes can be estimated from analysis of FSC signal
      distribution in flow cytometry. Previously, Pearson's coefficient of dissymmetry
      (PCD) and spherical index (SphI) were applied to determine erythrocyte sphericity
      from the FSC histogram. The aim of the present study is to illustrate the
      application of kurtosis as an indicator of erythrocyte sphericity in flow
      cytometry in a broad range of FSC distributions. Moreover, the possibility of
      longitudinal evaluation of erythrocyte sphericity is studied. Change of
      erythrocyte sphericity of 10 healthy subjects was induced by variation of buffer
      osmolarity to validate applicability of sphericity measures. Agreement between
      the sphericity indicators was then studied in samples from 20 healthy donors
      taken at three time points, which were processed through density gradient
      centrifugation and incubated with FITC-labelled antibodies to induce a broad
      variation of erythrocyte form (1086 samples). SphI, PCD and kurtosis of FSC
      distribution were calculated. Correlation of the respective measures, standard
      error of measurement (SEM) and r ratio (intra- to interindividual variance) were
      determined to illustrate agreement between the sphericity indicators. In the
      first study part, all sphericity indicators illustrated change of erythrocyte
      shape as induced by osmolarity variation. In the second part, correlation between
      kurtosis and SphI was -0.97 and correlation between kurtosis and PCD was 0.58
      (p<0.05). In isotype control samples, correlation between kurtosis and SphI was 
      0.98 and correlation between kurtosis and PCD was 0.48 (p<0.05). In these
      samples, mean kurtosis was -0.80 (SEM 0.03), mean SphI was 2.19 (SEM 0.04) and
      mean PCD was -0.31 (SEM 0.02). r ratios of all measures of sphericity were <0.6.
      Our results show that kurtosis is closely correlated with SphI in a broad range
      of erythrocyte FSC distributions. Moreover, all measures of sphericity feature r
      ratios <0.6, highlighting that erythrocyte sphericity appears as a feasible
      parameter for individual longitudinal data monitoring.

PMID- 23555812
TI  - Fetal human cytomegalovirus transmission correlates with delayed maternal
      antibodies to gH/gL/pUL128-130-131 complex during primary infection.
AB  - Primary human cytomegalovirus (HCMV) infections during pregnancy are associated
      with a high risk of virus transmission to the fetus. To identify correlates of
      intrauterine HCMV transmission, serial serum samples from HCMV transmitter and
      non-transmitter pregnant women with primary HCMV infection were analyzed for the
      presence of neutralizing antibodies against different glycoproteins and
      glycoprotein complexes, which are known to mediate entry into distinct types of
      host cells. Neutralizing activity was detected in the sera early after primary
      infection; absorption with a soluble pentameric complex formed by gH/gL/pUL128
      131, but not with gH/gL dimer or with gB, abolished the capacity of sera to
      neutralize infection of epithelial cells. Importantly, an early, high antibody
      response to pentamer antigenic sites was associated with a significantly reduced
      risk of HCMV transmission to the fetus. This association is consistent with the
      high in vitro inhibition of HCMV infection of epithelial/endothelial cells as
      well as cell-to-cell spreading and virus transfer to leukocytes by anti-pentamer
      antibodies. Taken together, these findings indicate that the HCMV pentamer
      complex is a major target of the antibody-mediated maternal immunity.

PMID- 23555813
TI  - The geometry of locomotive behavioral states in C. elegans.
AB  - We develop a new hidden Markov model-based method to analyze C elegans locomotive
      behavior and use this method to quantitatively characterize behavioral states. In
      agreement with previous work, we find states corresponding to roaming, dwelling,
      and quiescence. However, we also find evidence for a continuum of intermediate
      states. We suggest that roaming, dwelling, and quiescence may best be thought of
      as extremes which, mixed in any proportion, define the locomotive repertoire of C
      elegans foraging and feeding behavior.

PMID- 23555814
TI  - The Smc5/Smc6/MAGE complex confers resistance to caffeine and genotoxic stress in
      Drosophila melanogaster.
AB  - The SMC5/6 protein complex consists of the Smc5, Smc6 and Non-Smc-Element (Nse)
      proteins and is important for genome stability in many species. To identify novel
      components in the DNA repair pathway, we carried out a genetic screen to identify
      mutations that confer reduced resistance to the genotoxic effects of caffeine,
      which inhibits the ATM and ATR DNA damage response proteins. This approach
      identified inactivating mutations in CG5524 and MAGE, homologs of genes encoding
      Smc6 and Nse3 in yeasts. The fact that Smc5 mutants are also caffeine-sensitive
      and that Mage physically interacts with Drosophila homologs of Nse proteins
      suggests that the structure of the Smc5/6 complex is conserved in Drosophila.
      Although Smc5/6 proteins are required for viability in S. cerevisiae, they are
      not essential under normal circumstances in Drosophila. However, flies carrying
      mutations in Smc5, Smc6 and MAGE are hypersensitive to genotoxic agents such as
      ionizing radiation, camptothecin, hydroxyurea and MMS, consistent with the Smc5/6
      complex serving a conserved role in genome stability. We also show that mutant
      flies are not compromised for pre-mitotic cell cycle checkpoint responses.
      Rather, caffeine-induced apoptosis in these mutants is exacerbated by inhibition
      of ATM or ATR checkpoint kinases but suppressed by Rad51 depletion, suggesting a
      functional interaction involving homologous DNA repair pathways that deserves
      further scrutiny. Our insights into the SMC5/6 complex provide new challenges for
      understanding the role of this enigmatic chromatin factor in multi-cellular
      organisms.

PMID- 23555815
TI  - Improved methods for reprogramming human dermal fibroblasts using fluorescence
      activated cell sorting.
AB  - Current methods to derive induced pluripotent stem cell (iPSC) lines from human
      dermal fibroblasts by viral infection rely on expensive and lengthy protocols.
      One major factor contributing to the time required to derive lines is the ability
      of researchers to identify fully reprogrammed unique candidate clones from a
      mixed cell population containing transformed or partially reprogrammed cells and
      fibroblasts at an early time point post infection. Failure to select high quality
      colonies early in the derivation process results in cell lines that require
      increased maintenance and unreliable experimental outcomes. Here, we describe an
      improved method for the derivation of iPSC lines using fluorescence activated
      cell sorting (FACS) to isolate single cells expressing the cell surface marker
      signature CD13(NEG)SSEA4(POS)Tra-1-60(POS) on day 7-10 after infection. This
      technique prospectively isolates fully reprogrammed iPSCs, and depletes both
      parental and "contaminating" partially reprogrammed fibroblasts, thereby
      substantially reducing the time and reagents required to generate iPSC lines
      without the use of defined small molecule cocktails. FACS derived iPSC lines
      express common markers of pluripotency, and possess spontaneous differentiation
      potential in vitro and in vivo. To demonstrate the suitability of FACS for high
      throughput iPSC generation, we derived 228 individual iPSC lines using either
      integrating (retroviral) or non- integrating (Sendai virus) reprogramming vectors
      and performed extensive characterization on a subset of those lines. The iPSC
      lines used in this study were derived from 76 unique samples from a variety of
      tissue sources, including fresh or frozen fibroblasts generated from biopsies
      harvested from healthy or disease patients.

PMID- 23555816
TI  - Investigation of oncogenic cooperation in simple liver-specific transgenic mouse
      models using noninvasive in vivo imaging.
AB  - Liver cancer is a complex multistep process requiring genetic alterations in
      multiple proto-oncogenes and tumor suppressor genes. Although hundreds of genes
      are known to play roles in hepatocarcinogenesis, oncogenic collaboration among
      these genes is still largely unknown. Here, we report a simple methodology by
      which oncogenic cooperation between cancer-related genes can be efficiently
      investigated in the liver. We developed various non-germline transgenic mouse
      models using hydrodynamics-based transfection which express HrasG12V, SmoM2, and
      a short-hairpin RNA down-regulating p53 (shp53) individually or in combination in
      the liver. In this transgenic system, firefly luciferase was co-expressed with
      the oncogenes as a reporter, allowing tumor growth in the liver to be monitored
      over time without an invasive procedure. Very strong bioluminescence imaging
      (BLI) signals were observed at 4 weeks post-hydrodynamic injection (PHI) in mice
      co-expressing HrasG12V and shp53, while only background signals were detected in
      other double or single transgenic groups until 30 weeks PHI. Consistent with the
      BLI data, tumors were observed in the HrasG12V plus shp53 group at 4 weeks PHI,
      while other transgenic groups failed to exhibit a hyperplastic nodule at 30 weeks
      PHI. In the HrasG12V plus shp53 transgenic group, BLI signals were well
      correlated with actual tumor growth in the liver, confirming the versatility of
      BLI-based monitoring of tumor growth in this organ. The methodology described
      here is expected to accelerate and facilitate in vivo studies of the
      hepatocarcinogenic potential of cancer-related genes by means of oncogenic
      cooperation.

PMID- 23555817
TI  - Gene expression in brain and liver produced by three different regimens of
      alcohol consumption in mice: comparison with immune activation.
AB  - Chronically available alcohol escalates drinking in mice and a single injection
      of the immune activator lipopolysaccharide can mimic this effect and result in a
      persistent increase in alcohol consumption. We hypothesized that chronic alcohol
      drinking and lipopolysaccharide injections will produce some similar molecular
      changes that play a role in regulation of alcohol intake. We investigated the
      molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult
      by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We
      identified similar patterns of transcriptional changes among four groups of
      animals, three consuming alcohol (vs water) in different consumption tests and
      one injected with lipopolysaccharide (vs. vehicle). The three tests of alcohol
      consumption are the continuous chronic two bottle choice (Chronic), two bottle
      choice available every other day (Chronic Intermittent) and limited access to one
      bottle of ethanol (Drinking in the Dark). Gene expression changes were more
      numerous and marked in liver than in prefrontal cortex for the alcohol treatments
      and similar in the two tissues for lipopolysaccharide. Many of the changes were
      unique to each treatment, but there was significant overlap in prefrontal cortex
      for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide
      and in liver all pairs showed overlap. In silico cell-type analysis indicated
      that lipopolysaccharide had strongest effects on brain microglia and liver
      Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine
      related (PPP1R1B, DRD1, DRD2, FOSB, PDNY) network that was highly over
      represented in the Chronic Intermittent group, with several genes from the
      network being also regulated in the Chronic and lipopolysaccharide (but not
      Drinking in the Dark) groups. Liver showed a CYP and GST centered metabolic
      network shared in part by all four treatments. We demonstrate common consequences
      of chronic alcohol consumption and immune activation in both liver and brain and
      show distinct genomic consequences of different types of alcohol consumption.

PMID- 23555818
TI  - GLTP mediated non-vesicular GM1 transport between native membranes.
AB  - Lipid transfer proteins (LTPs) are emerging as key players in lipid homeostasis
      by mediating non-vesicular transport steps between two membrane surfaces. Little
      is known about the driving force that governs the direction of transport in
      cells. Using the soluble LTP glycolipid transfer protein (GLTP), we examined GM1
      (monosialotetrahexosyl-ganglioside) transfer to native membrane surfaces. With
      artificial GM1 donor liposomes, GLTP can be used to increase glycolipid levels
      over natural levels in either side of the membrane leaflet, i.e., external or
      cytosolic. In a system with native donor- and acceptor-membranes, we find that
      GLTP balances highly variable GM1 concentrations in a population of membranes
      from one cell type, and in addition, transfers lipids between membranes from
      different cell types. Glycolipid transport is highly efficient, independent of
      cofactors, solely driven by the chemical potential of GM1 and not discriminating
      between the extra- and intracellular membrane leaflet. We conclude that GLTP
      mediated non-vesicular lipid trafficking between native membranes is driven by
      simple thermodynamic principles and that for intracellular transport less than 1
      uM GLTP would be required in the cytosol. Furthermore, the data demonstrates the
      suitability of GLTP as a tool for artificially increasing glycolipid levels in
      cellular membranes.

PMID- 23555819
TI  - Broadband transmission EPR spectroscopy.
AB  - EPR spectroscopy employs a resonator operating at a single microwave frequency
      and phase-sensitive detection using modulation of the magnetic field. The X-band
      spectrometer is the general standard with a frequency in the 9-10 GHz range. Most
      (bio)molecular EPR spectra are determined by a combination of the frequency
      dependent electronic Zeeman interaction and a number of frequency-independent
      interactions, notably, electron spin - nuclear spin interactions and electron
      spin - electron spin interactions, and unambiguous analysis requires data
      collection at different frequencies. Extant and long-standing practice is to use
      a different spectrometer for each frequency. We explore the alternative of
      replacing the narrow-band source plus single-mode resonator with a continuously
      tunable microwave source plus a non-resonant coaxial transmission cell in an
      unmodulated external field. Our source is an arbitrary wave digital signal
      generator producing an amplitude-modulated sinusoidal microwave in combination
      with a broadband amplifier for 0.8-2.7 GHz. Theory is developed for coaxial
      transmission with EPR detection as a function of cell dimensions and materials.
      We explore examples of a doublet system, a high-spin system, and an integer-spin
      system. Long, straigth, helical, and helico-toroidal cells are developed and
      tested with dilute aqueous solutions of spin label hydroxy-tempo. A detection
      limit of circa 5 uM HO-tempo in water at 800 MHz is obtained for the present
      setup, and possibilities for future improvement are discussed.

PMID- 23555820
TI  - Nutrition metabolism plays an important role in the alternate bearing of the
      olive tree (Olea europaea L.).
AB  - The olive tree (Olea europaea L.) is widely known for its strong tendency for
      alternate bearing, which severely affects the fruit yield from year to year.
      Microarray based gene expression analysis using RNA from olive samples (on-off
      years leaves and ripe-unripe fruits) are particularly useful to understand the
      molecular mechanisms influencing the periodicity in the olive tree. Thus, we
      carried out genome wide transcriptome analyses involving different organs and
      temporal stages of the olive tree using the NimbleGen Array containing 136,628
      oligonucleotide probe sets. Cluster analyses of the genes showed that cDNAs
      originated from different organs could be sorted into separate groups. The
      nutritional control had a particularly remarkable impact on the alternate bearing
      of olive, as shown by the differential expression of transcripts under different
      temporal phases and organs. Additionally, hormonal control and flowering
      processes also played important roles in this phenomenon. Our analyses provide
      further insights into the transcript changes between "on year" and "off year"
      leaves along with the changes from unrpipe to ripe fruits, which shed light on
      the molecular mechanisms underlying the olive tree alternate bearing. These
      findings have important implications for the breeding and agriculture of the
      olive tree and other crops showing periodicity. To our knowledge, this is the
      first study reporting the development and use of an olive array to document the
      gene expression profiling associated with the alternate bearing in olive tree.

PMID- 23555821
TI  - Deep cerebellar nuclei play an important role in two-tone discrimination on delay
      eyeblink conditioning in C57BL/6 mice.
AB  - Previous studies have shown that deep cerebellar nuclei (DCN)-lesioned mice
      develop conditioned responses (CR) on delay eyeblink conditioning when a salient
      tone conditioned stimulus (CS) is used, which suggests that the cerebellum
      potentially plays a role in more complicated cognitive functions. In the present
      study, we examined the role of DCN in tone frequency discrimination in the delay
      eyeblink-conditioning paradigm. In the first experiment, DCN-lesioned and sham
      operated mice were subjected to standard simple eyeblink conditioning under low
      frequency tone CS (LCS: 1 kHz, 80 dB) or high-frequency tone CS (HCS: 10 kHz, 70
      dB) conditions. DCN-lesioned mice developed CR in both CS conditions as well as
      sham-operated mice. In the second experiment, DCN-lesioned and sham-operated mice
      were subjected to two-tone discrimination tasks, with LCS+ (or HCS+) paired with
      unconditioned stimulus (US), and HCS- (or LCS-) without US. CR% in sham-operated
      mice increased in LCS+ (or HCS+) trials, regardless of tone frequency of CS, but
      not in HCS- (or LCS-) trials. The results indicate that sham-operated mice can
      discriminate between LCS+ and HCS- (or HCS+ and LCS-). In contrast, DCN-lesioned
      mice showed high CR% in not only LCS+ (or HCS+) trials but also HCS- (or LCS-)
      trials. The results indicate that DCN lesions impair the discrimination between
      tone frequency in eyeblink conditioning. Our results suggest that the cerebellum
      plays a pivotal role in the discrimination of tone frequency.

PMID- 23555822
TI  - Metabolism of BYZX in human liver microsomes and cytosol: identification of the
      metabolites and metabolic pathways of BYZX.
AB  - BYZX, [(E)-2-(4-((diethylamino)methyl)benzylidene)-5,6-dimethoxy-2,3-dihydroinden
      one], belongs to a series of novel acetylcholinesterase inhibitors and has been
      synthesized as a new chemical entity for the treatment of Alzheimer's disease
      symptoms. When incubated with human liver microsomes (HLMs), BYZX was rapidly
      transformed into its metabolites M1, M2, and M3. The chemical structures of these
      metabolites were identified using liquid chromatography tandem mass spectrometry
      and nuclear magnetic resonance, which indicated that M1 was an N-desethylated and
      C = C hydrogenation metabolite of BYZX. M2 and M3 were 2 precursor metabolites,
      which resulted from the hydrogenation and desethylation of BYZX, respectively.
      Further studies with chemical inhibitors and human recombinant cytochrome P450s
      (CYPs), and correlation studies were performed. The results indicated that the N
      desethylation of BYZX and M2 was mediated by CYP3A4 and CYP2C8. The reduced form
      of beta-nicotinamide adenine dinucleotide 2'-phosphate was involved in the
      hydrogenation of BYZX and M3, and this reaction occurred in the HLMs and in the
      human liver cytosol. The hydrogenation reaction was not inhibited by any chemical
      inhibitors of CYPs, but it was significantly inhibited by some substrates of
      alpha,beta-ketoalkene C = C reductases and their inhibitors such as
      benzylideneacetone, dicoumarol, and indomethacin. Our results suggest that
      alpha,beta-ketoalkene C = C reductases may play a role in the hydrogenation
      reaction, but this issue requires further clarification.

PMID- 23555823
TI  - Polypeptone induces dramatic cell lysis in ura4 deletion mutants of fission
      yeast.
AB  - Polypeptone is widely excluded from Schizosaccharomyces pombe growth medium.
      However, the reasons why polypeptone should be avoided have not been documented.
      Polypeptone dramatically induced cell lysis in the ura4 deletion mutant when
      cells approached the stationary growth phase, and this phenotype was suppressed
      by supplementation of uracil. To determine the specificity of this cell lysis
      phenotype, we created deletion mutants of other genes involved in de novo
      biosynthesis of uridine monophosphate (ura1, ura2, ura3, and ura5). Cell lysis
      was not observed in these gene deletion mutants. In addition, concomitant
      disruption of ura1, ura2, ura3, or ura5 in the ura4 deletion mutant suppressed
      cell lysis, indicating that cell lysis induced by polypeptone is specific to the
      ura4 deletion mutant. Furthermore, cell lysis was also suppressed when the gene
      involved in coenzyme Q biosynthesis was deleted. This is likely because Ura3
      requires coenzyme Q for its activity. The ura4 deletion mutant was sensitive to
      zymolyase, which mainly degrades (1,3)-beta-D glucan, when grown in the presence
      of polypeptone, and cell lysis was suppressed by the osmotic stabiliser,
      sorbitol. Finally, the induction of cell lysis in the ura4 deletion mutant was
      due to the accumulation of orotidine-5-monophosphate. Cell wall integrity was
      dramatically impaired in the ura4 deletion mutant when grown in the presence of
      polypeptone. Because ura4 is widely used as a selection marker in S. pombe,
      caution needs to be taken when evaluating phenotypes of ura4 mutants.

PMID- 23555825
TI  - High yield production of influenza virus in Madin Darby canine kidney (MDCK)
      cells with stable knockdown of IRF7.
AB  - Influenza is a serious public health problem that causes a contagious respiratory
      disease. Vaccination is the most effective strategy to reduce transmission and
      prevent influenza. In recent years, cell-based vaccines have been developed with
      continuous cell lines such as Madin-Darby canine kidney (MDCK) and Vero. However,
      wild-type influenza and egg-based vaccine seed viruses will not grow efficiently
      in these cell lines. Therefore, improvement of virus growth is strongly required
      for development of vaccine seed viruses and cell-based influenza vaccine
      production. The aim of our research is to develop novel MDCK cells supporting
      highly efficient propagation of influenza virus in order to expand the capacity
      of vaccine production. In this study, we screened a human siRNA library that
      involves 78 target molecules relating to three major type I interferon (IFN)
      pathways to identify genes that when knocked down by siRNA lead to enhanced
      production of influenza virus A/Puerto Rico/8/1934 in A549 cells. The siRNAs
      targeting 23 candidate genes were selected to undergo a second screening pass in
      MDCK cells. We examined the effects of knockdown of target genes on the viral
      production using newly designed siRNAs based on sequence analyses. Knockdown of
      the expression of a canine gene corresponding to human IRF7 by siRNA increased
      the efficiency of viral production in MDCK cells through an unknown process that
      includes the mechanisms other than inhibition of IFN-alpha/beta induction.
      Furthermore, the viral yield greatly increased in MDCK cells stably transduced
      with the lentiviral vector for expression of short hairpin RNA against IRF7
      compared with that in control MDCK cells. Therefore, we propose that modified
      MDCK cells with lower expression level of IRF7 could be useful not only for
      increasing the capacity of vaccine production but also facilitating the process
      of seed virus isolation from clinical specimens for manufacturing of vaccines.

PMID- 23555824
TI  - Resveratrol inhibits beta-amyloid-induced neuronal apoptosis through regulation
      of SIRT1-ROCK1 signaling pathway.
AB  - Alzheimer's disease (AD) is characterized by the accumulation of beta-amyloid
      peptide (Abeta) and loss of neurons. Recently, a growing body of evidences have
      indicated that as a herbal compound naturally derived from grapes, resveratrol
      modulates the pathophysiology of AD, however, with a largely unclear mechanism.
      Therefore, we aimed to investigate the protection of resveratrol against the
      neurotoxicity of beta-amyloid peptide 25-35 (Abeta(25-35)) and further explore
      its underlying mechanism in the present study. PC12 cells were injuried by
      Abeta(25-35), and resveratrol at different concentrations was added into the
      culture medium. We observed that resveratrol increased cell viability through the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate
      dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction
      of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the
      intercellular Ca(2+) homeostasis and attenuated Abeta(25-35) neurotoxicity.
      Additionally, Abeta(25-35)-suppressed silent information regulator 1 (SIRT1)
      activity was significantly reversed by resveratrol, resulting in the
      downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed
      that resveratrol significantly protected PC12 cells and inhibited the beta
      amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a
      downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken
      together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role
      in the pathomechanism of AD.

PMID- 23555826
TI  - Strict or graduated punishment? Effect of punishment strictness on the evolution
      of cooperation in continuous public goods games.
AB  - Whether costly punishment encourages cooperation is one of the principal
      questions in studies on the evolution of cooperation and social sciences. In
      society, punishment helps deter people from flouting rules in institutions.
      Specifically, graduated punishment is a design principle for long-enduring common
      pool resource institutions. In this study, we investigate whether graduated
      punishment can promote a higher cooperation level when each individual plays the
      public goods game and has the opportunity to punish others whose cooperation
      levels fall below the punisher's threshold. We then examine how spatial structure
      affects evolutionary dynamics when each individual dies inversely proportional to
      the game score resulting from the social interaction and another player is
      randomly chosen from the population to produce offspring to fill the empty site
      created after a player's death. Our evolutionary simulation outcomes demonstrate
      that stricter punishment promotes increased cooperation more than graduated
      punishment in a spatially structured population, whereas graduated punishment
      increases cooperation more than strict punishment when players interact with
      randomly chosen opponents from the population. The mathematical analysis also
      supports the results.

PMID- 23555827
TI  - Altered default network resting-state functional connectivity in adolescents with
      Internet gaming addiction.
AB  - PURPOSE: Excessive use of the Internet has been linked to a variety of negative
      psychosocial consequences. This study used resting-state functional magnetic
      resonance imaging (fMRI) to investigate whether functional connectivity is
      altered in adolescents with Internet gaming addiction (IGA). METHODS: Seventeen
      adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute
      resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was
      determined in all subjects by investigating synchronized low-frequency fMRI
      signal fluctuations using a temporal correlation method. To assess the
      relationship between IGA symptom severity and PCC connectivity, contrast images
      representing areas correlated with PCC connectivity were correlated with the
      scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS)
      and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per
      week. RESULTS: There were no significant differences in the distributions of the
      age, gender, and years of education between the two groups. The subjects with IGA
      showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001)
      and BIS-11 (p = 0.01) scores than the controls. Compared with the control group,
      subjects with IGA exhibited increased functional connectivity in the bilateral
      cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior
      parietal lobule and right inferior temporal gyrus exhibited decreased
      connectivity. Connectivity with the PCC was positively correlated with CIAS
      scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate,
      nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively
      correlated with the right cerebellum anterior lobe and left superior parietal
      lobule. CONCLUSION: Our results suggest that adolescents with IGA exhibit
      different resting-state patterns of brain activity. As these alterations are
      partially consistent with those in patients with substance addiction, they
      support the hypothesis that IGA as a behavioral addiction that may share similar
      neurobiological abnormalities with other addictive disorders.

PMID- 23555828
TI  - An appraisal of human mitochondrial DNA instability: new insights into the role
      of non-canonical DNA structures and sequence motifs.
AB  - Mitochondrial DNA (mtDNA) deletion mutations are frequently observed in aged
      postmitotic tissues and are the cause of a wide range of human disorders.
      Presently, the molecular bases underlying mtDNA deletion formation remain a
      matter of intense debate, and it is commonly accepted that several mechanisms
      contribute to the spectra of mutations in the mitochondrial genome. In this work
      we performed an extensive screening of human mtDNA deletions and evaluated the
      association between breakpoint density and presence of non-canonical DNA elements
      and over-represented sequence motifs. Our observations support the involvement of
      helix-distorting intrinsically curved regions and long G-tetrads in eliciting
      instability events. In addition, higher breakpoint densities were consistently
      observed within GC-skewed regions and in the close vicinity of the degenerate
      sequence motif YMMYMNNMMHM. A parallelism is also established with hot spot
      motifs previously identified in the nuclear genome, as well as with the minimal
      binding site for the mitochondrial transcription termination factor mTERF. This
      study extends the current knowledge on the mechanisms driving mitochondrial
      rearrangements and opens up exciting avenues for further research.

PMID- 23555829
TI  - Florida harvester ant nest architecture, nest relocation and soil carbon dioxide
      gradients.
AB  - Colonies of the Florida harvester ant, Pogonomyrmex badius, excavate species
      typical subterranean nests up the 3 m deep with characteristic vertical
      distribution of chamber area/shape, spacing between levels and vertical
      arrangement of the ants by age and brood stage. Colonies excavate and occupy a
      new nest about once a year, and doing so requires that they have information
      about the depth below ground. Careful excavation and mapping of vacated and new
      nests revealed that there was no significant difference between the old and new
      nests in any measure of nest size, shape or arrangement. Colonies essentially
      built a replicate of the just-vacated nest (although details differed), and they
      did so in less than a week. The reason for nest relocation is not apparent.
      Tschinkel noted that the vertical distribution of chamber area, worker age and
      brood type was strongly correlated to the soil carbon dioxide gradient, and
      proposed that this gradient serves as a template for nest excavation and vertical
      distribution. To test this hypothesis, the carbon dioxide gradient of colonies
      that were just beginning to excavate a new nest was eliminated by boring 6 vent
      holes around the forming nest, allowing the soil CO2 to diffuse into the
      atmosphere and eliminating the gradient. Sadly, neither the nest architecture nor
      the vertical ant distribution of vented nests differed from either unvented
      control or from their own vacated nest. In a stronger test, workers excavated a
      new nest under a reversed carbon dioxide gradient (high concentration near the
      surface, low below). Even under these conditions, the new and old nests did not
      differ significantly, showing that the soil carbon dioxide gradient does not
      serve as a template for nest construction or vertical worker distribution. The
      possible importance of soil CO2 gradients for soil-dwelling animals is discussed.

PMID- 23555830
TI  - Stylet morphometrics and citrus leaf vein structure in relation to feeding
      behavior of the Asian citrus psyllid Diaphorina citri, vector of citrus
      huanglongbing bacterium.
AB  - The Asian citrus psyllid (ACP), Diaphorina citri (Hemiptera: Psyllidae), is the
      primary vector of the phloem-limited bacterium Candidatus Liberibacter asiaticus
      (LAS) associated with huanglongbing (HLB, citrus greening), considered the
      world's most serious disease of citrus. Stylet morphometrics of ACP nymphs and
      adults were studied in relation to citrus vein structure and to their putative
      (histologically verified) feeding sites on Valencia orange leaves. ACP nymphs
      preferred to settle and feed on the lower (abaxial) side of young leaves either
      on secondary veins or on the sides of the midrib, whereas adults preferred to
      settle and feed on the upper (adaxial) or lower secondary veins of young or old
      leaves. Early instar nymphs can reach and probe the phloem probably because the
      distance to the phloem is considerably shorter in younger than in mature leaves,
      and is shorter from the sides of the midrib compared to that from the center.
      Additionally, the thick-walled 'fibrous ring' (sclerenchyma) around the phloem,
      which may act as a barrier to ACP stylet penetration into the phloem, is more
      prominent in older than in younger leaves and in the center than on the sides of
      the midrib. The majority (80-90%) of the salivary sheath termini produced by ACP
      nymphs and adults that reached a vascular bundle were associated with the phloem,
      whereas only 10-20% were associated with xylem vessels. Ultrastructural studies
      on ACP stylets and LAS-infected leaves suggested that the width of the maxillary
      food canal in first instar nymphs is wide enough for LAS bacteria to traverse
      during food ingestion (and LAS acquisition). However, the width of the maxillary
      salivary canal in these nymphs may not be wide enough to accommodate LAS bacteria
      during salivation (and LAS inoculation) into host plants. This may explain the
      inability of early instar nymphs to transmit LAS/HLB in earlier reports.

PMID- 23555831
TI  - Whole genome sequence analysis of the first Australian OXA-48-producing outbreak
      associated Klebsiella pneumoniae isolates: the resistome and in vivo evolution.
AB  - Whole genome sequencing was used to characterize the resistome of intensive care
      unit (ICU) outbreak-associated carbapenem-resistant K. pneumoniae isolates.
      Importantly, and of particular concern, the carbapenem-hydrolyzing beta-lactamase
      gene bla(OXA-48) and the extended-spectrum beta-lactamase gene bla(CTX-M-14),
      were identified on a single broad host-range conjugative plasmid. This represents
      the first report of bla(OXA-48) in Australia and highlights the importance of
      resistance gene surveillance, as such plasmids can silently spread amongst
      enterobacterial populations and have the potential to drastically limit treatment
      options. Furthermore, the in vivo evolution of these isolates was also examined
      after 18 months of intra-abdominal carriage in a patient that transited through
      the ICU during the outbreak period. Reflecting the clonality of K. pneumoniae,
      only 11 single nucleotide polymorphisms (SNPs) were accumulated during this time
      period and many of these were associated with genes involved in
      tolerance/resistance to antibiotics, metals or organic solvents, and
      transcriptional regulation. Collectively, these SNPs are likely to be associated
      with changes in virulence (at least to some extent) that have refined the in vivo
      colonization capacity of the original outbreak isolate.

PMID- 23555832
TI  - Environmentally induced epigenetic transgenerational inheritance of altered
      Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.
AB  - Environmental toxicants have been shown to induce the epigenetic
      transgenerational inheritance of adult onset disease, including testis disease
      and male infertility. The current study was designed to determine the impact of
      an altered sperm epigenome on the subsequent development of an adult somatic cell
      (Sertoli cell) that influences the onset of a specific disease (male
      infertility). A gestating female rat (F0 generation) was exposed to the
      agriculture fungicide vinclozolin during gonadal sex determination and then the
      subsequent F3 generation progeny used for the isolation of Sertoli cells and
      assessment of testis disease. As previously observed, enhanced spermatogenic cell
      apoptosis was observed. The Sertoli cells provide the physical and nutritional
      support for the spermatogenic cells. Over 400 genes were differentially expressed
      in the F3 generation control versus vinclozolin lineage Sertoli cells. A number
      of specific cellular pathways were identified to be transgenerationally altered.
      One of the key metabolic processes affected was pyruvate/lactate production that
      is directly linked to spermatogenic cell viability. The Sertoli cell epigenome
      was also altered with over 100 promoter differential DNA methylation regions
      (DMR) modified. The genomic features and overlap with the sperm DMR were
      investigated. Observations demonstrate that the transgenerational sperm
      epigenetic alterations subsequently alters the development of a specific somatic
      cell (Sertoli cell) epigenome and transcriptome that correlates with adult onset
      disease (male infertility). The environmentally induced epigenetic
      transgenerational inheritance of testis disease appears to be a component of the
      molecular etiology of male infertility.

PMID- 23555833
TI  - Parental weight perceptions: a cause for concern in the prevention and management
      of childhood obesity in the United Arab Emirates.
AB  - Parental participation is a key factor in the prevention and management of
      childhood obesity, thus parental recognition of weight problems is essential. We
      estimated parental perceptions and their determinants in the Emirati population.
      We invited 1541 students (grade 1-12; 50% boys) and their parents, but only 1440
      (6-19 years) and their parents consented. Of these, 945 Emirati nationals
      provided data for analysis. Anthropometric and demographic variables were
      measured by standard methods. CDC BMI percentile charts for age and sex were used
      to classify children's weight. Parental perception of their children's weight
      status (underweight, normal, and overweight/obese) was recorded. Logistic
      regression analyses were used to identify independent predictors of parental
      perceptions of children's weight status. Of all parents, 33.8% misclassified
      their children's' weight status; underestimating (27.4%) or overestimating
      (6.3%). Misclassification was highest among parents of overweight/obese children
      (63.5%) and underweight (55.1%) children. More importantly, parental perceptions
      of their children being overweight or obese, among truly overweight/obese
      children, i.e. correct identification of an overweight/obese child as such, were
      associated with the true child's BMI percentile (CDC) with an OR of 1.313 (95%
      CI: 1.209-1.425; p<0.001) per percentile point, but not age, parental education,
      household income, and child's sex. We conclude that the majority of parents of
      overweight/obese children either overestimated or, more commonly, underestimated
      children's weight status. Predictors of accurate parental perception, in this
      population, include the true children's BMI, but not age, household income, and
      sex. Thus, parents having an incorrect perception of their child's weight status
      may ignore otherwise appropriate health messages.

PMID- 23555834
TI  - Identification and functional analysis of GJA8 mutation in a Chinese family with
      autosomal dominant perinuclear cataracts.
AB  - Congenital cataract is a clinically and genetically heterogeneous group of eye
      disorders that causes visual impairment and childhood blindness. The purpose of
      this study was to identify the genetic defect associated with autosomal dominant
      congenital perinuclear cataract in a Chinese family. A detailed family history
      and clinical data of the family were recorded, and candidate gene sequencing was
      performed to screen for mutation-causing disease in our study. Direct sequencing
      revealed a c.601G>A (p.E201K) transversion in exon 2 of GJA8. This mutation co
      segregated with all affected individuals in the family and was not found in
      unaffected family members or 100 unrelated controls. The function and mechanism
      of novel GJA8 point mutation E201K in Chinese patients were then investigated in
      this study. We found E201K aberrantly located in cytoplasm and prevented its
      location in the plasma membrane. Induction of E201K expression led to a decrease
      in cell growth and viability by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay. Our study provides important evidence that
      GJA8 is a disease-causing gene for congenital cataract and that mutation of GJA8
      has a potential causative effect.

PMID- 23555835
TI  - Pyrosequencing reveals high-temperature cellulolytic microbial consortia in Great
      Boiling Spring after in situ lignocellulose enrichment.
AB  - To characterize high-temperature cellulolytic microbial communities, two
      lignocellulosic substrates, ammonia fiber-explosion-treated corn stover and aspen
      shavings, were incubated at average temperatures of 77 and 85 degrees C in the
      sediment and water column of Great Boiling Spring, Nevada. Comparison of 109,941
      quality-filtered 16S rRNA gene pyrosequences (pyrotags) from eight enrichments to
      37,057 quality-filtered pyrotags from corresponding natural samples revealed
      distinct enriched communities dominated by phylotypes related to cellulolytic and
      hemicellulolytic Thermotoga and Dictyoglomus, cellulolytic and sugar-fermenting
      Desulfurococcales, and sugar-fermenting and hydrogenotrophic Archaeoglobales.
      Minor enriched populations included close relatives of hydrogenotrophic
      Thermodesulfobacteria, the candidate bacterial phylum OP9, and candidate archaeal
      groups C2 and DHVE3. Enrichment temperature was the major factor influencing
      community composition, with a negative correlation between temperature and
      richness, followed by lignocellulosic substrate composition. This study
      establishes the importance of these groups in the natural degradation of
      lignocellulose at high temperatures and suggests that a substantial portion of
      the diversity of thermophiles contributing to consortial cellulolysis may be
      contained within lineages that have representatives in pure culture.

PMID- 23555836
TI  - A correlational study of scoliosis and trunk balance in adult patients with
      mandibular deviation.
AB  - Previous studies have confirmed that patients with mandibular deviation often
      have abnormal morphology of their cervical vertebrae. However, the relationship
      between mandibular deviation, scoliosis, and trunk balance has not been studied.
      Currently, mandibular deviation is usually treated as a single pathology, which
      leads to poor clinical efficiency. We investigated the relationship of spine
      coronal morphology and trunk balance in adult patients with mandibular deviation,
      and compared the finding to those in healthy volunteers. 35 adult patients with
      skeletal mandibular deviation and 10 healthy volunteers underwent anterior X-ray
      films of the head and posteroanterior X-ray films of the spine. Landmarks and
      lines were drawn and measured on these films. The axis distance method was used
      to measure the degree of scoliosis and the balance angle method was used to
      measure trunk balance. The relationship of mandibular deviation, spine coronal
      morphology and trunk balance was evaluated with the Pearson correlation method.
      The spine coronal morphology of patients with mandibular deviation demonstrated
      an "S" type curve, while a straight line parallel with the gravity line was found
      in the control group (significant difference, p<0.01). The trunk balance of
      patients with mandibular deviation was disturbed (imbalance angle >1 degrees ),
      while the control group had a normal trunk balance (imbalance angle <1 degrees ).
      There was a significant difference between the two groups (p<0.01). The degree of
      scoliosis and shoulder imbalance correlated with the degree of mandibular
      deviation, and presented a linear trend. The direction of mandibular deviation
      was the same as that of the lateral bending of thoracolumbar vertebrae, which was
      opposite to the direction of lateral bending of cervical vertebrae. Our study
      shows the degree of mandibular deviation has a high correlation with the degree
      of scoliosis and trunk imbalance, all the three deformities should be clinically
      evaluated in the management of mandibular deviation.

PMID- 23555837
TI  - Genetic interactions between neurofibromin and endothelin receptor B in mice.
AB  - When mutations in two different genes produce the same mutant phenotype, it
      suggests that the encoded proteins either interact with each other, or act in
      parallel to fulfill a similar purpose. Haploinsufficiency of Neurofibromin and
      over-expression of Endothelin 3 both cause increased numbers of melanocytes to
      populate the dermis during mouse development, and thus we are interested in how
      these two signaling pathways might intersect. Neurofibromin is mutated in the
      human genetic disease, neurofibromatosis type 1, which is characterized by the
      development of Schwann cell based tumors and skin hyper-pigmentation.
      Neurofibromin is a GTPase activating protein, while the Endothelin 3 ligand
      activates Endothelin receptor B, a G protein coupled receptor. In order to study
      the genetic interactions between endothelin and neurofibromin, we defined the
      deletion breakpoints of the classical Ednrb piebald lethal allele (Ednrb(s-l) )
      and crossed these mice to mice with a loss-of-function mutation in neurofibromin,
      Dark skin 9 (Dsk9). We found that Neurofibromin haploinsufficiency requires
      Endothelin receptor B to darken the tail dermis. In contrast, Neurofibromin
      haploinsufficiency increases the area of the coat that is pigmented in Endothelin
      receptor B null mice. We also found an oncogenic mutation in the G protein alpha
      subunit, GNAQ, which couples to Endothelin receptor B, in a uveal melanoma from a
      patient with neurofibromatosis type 1. Thus, this data suggests that there is a
      complex relationship between Neurofibromin and Endothelin receptor B.

PMID- 23555838
TI  - Age-dependent effects of oral infection with dengue virus on Aedes aegypti
      (Diptera: Culicidae) feeding behavior, survival, oviposition success and
      fecundity.
AB  - BACKGROUND: Aedes aegypti is the main vector of dengue, a disease that is
      increasing its geographical range as well as incidence rates. Despite its public
      health importance, the effect of dengue virus (DENV) on some mosquito traits
      remains unknown. Here, we investigated the impact of DENV-2 infection on the
      feeding behavior, survival, oviposition success and fecundity of Ae. aegypti
      females. METHODS/PRINCIPAL FINDINGS: After orally-challenging Ae. aegypti females
      with a DENV-2 strain using a membrane feeder, we monitored the feeding behavior,
      survival, oviposition success and fecundity throughout the mosquito lifespan. We
      observed an age-dependent cost of DENV infection on mosquito feeding behavior and
      fecundity. Infected individuals took more time to ingest blood from anesthetized
      mice in the 2(nd) and 3(rd) weeks post-infection, and also longer overall blood
      feeding times in the 3(rd) week post-infection, when females were around 20 days
      old. Often, infected Ae. aegypti females did not lay eggs and when they were
      laid, smaller number of eggs were laid compared to uninfected controls. A
      reduction in the number of eggs laid per female was evident starting on the 3(rd)
      week post-infection. DENV-2 negatively affected mosquito lifespan, since overall
      the longevity of infected females was halved compared to that of the uninfected
      control group. CONCLUSIONS: The DENV-2 strain tested significantly affected Ae.
      aegypti traits directly correlated with vectorial capacity or mosquito population
      density, such as feeding behavior, survival, fecundity and oviposition success.
      Infected mosquitoes spent more time ingesting blood, had reduced lifespan, laid
      eggs less frequently, and when they did lay eggs, the clutches were smaller than
      uninfected mosquitoes.

PMID- 23555840
TI  - Bevacizumab treatment for meningiomas in NF2: a retrospective analysis of 15
      patients.
AB  - Bevacizumab treatment can result in tumor shrinkage of progressive vestibular
      schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on
      meningiomas has not been defined. To determine the clinical activity of
      bevacizumab against NF2-related meningiomas, we measured changes in volume of
      meningiomas in NF2 patients who received bevacizumab for treatment of progressive
      vestibular schwannomas. A radiographic response was defined as a 20% decrease in
      tumor size by volumetric MRI analysis. In addition, we determined the expression
      pattern of growth factors associated with tumor angiogenesis in paraffin-embedded
      tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2
      patients were included in this study with a median follow up time of 18 months. A
      volumetric radiographic response was seen in 29% of the meningiomas (14/48).
      Tumor shrinkage was not durable: the median duration of response was 3.7 months
      and the median time to progression was 15 months. There was no significant
      correlation between pre-treatment growth rate and meningioma response in
      regression models. Tissue analysis showed no correlation between tumor
      microvascular density and expression of VEGF pathway components. This data
      suggests that, in contrast to schwannomas, activation of VEGF pathway is not the
      primary driver of angiogenesis in meningiomas. Our results suggest that a
      minority of NF2-associated meningiomas shrink during bevacizumab therapy and that
      these responses were of short duration. These results are comparable to previous
      studies of bevacizumab in sporadic meningiomas.

PMID- 23555839
TI  - Estimation of quasi-stiffness and propulsive work of the human ankle in the
      stance phase of walking.
AB  - Characterizing the quasi-stiffness and work of lower extremity joints is critical
      for evaluating human locomotion and designing assistive devices such as
      prostheses and orthoses intended to emulate the biological behavior of human
      legs. This work aims to establish statistical models that allow us to predict the
      ankle quasi-stiffness and net mechanical work for adults walking on level ground.
      During the stance phase of walking, the ankle joint propels the body through
      three distinctive phases of nearly constant stiffness known as the quasi
      stiffness of each phase. Using a generic equation for the ankle moment obtained
      through an inverse dynamics analysis, we identify key independent parameters
      needed to predict ankle quasi-stiffness and propulsive work and also the
      functional form of each correlation. These parameters include gait speed, ankle
      excursion, and subject height and weight. Based on the identified form of the
      correlation and key variables, we applied linear regression on experimental
      walking data for 216 gait trials across 26 subjects (speeds from 0.75-2.63 m/s)
      to obtain statistical models of varying complexity. The most general forms of the
      statistical models include all the key parameters and have an R(2) of 75% to 81%
      in the prediction of the ankle quasi-stiffnesses and propulsive work. The most
      specific models include only subject height and weight and could predict the
      ankle quasi-stiffnesses and work for optimal walking speed with average error of
      13% to 30%. We discuss how these models provide a useful framework and foundation
      for designing subject- and gait-specific prosthetic and exoskeletal devices
      designed to emulate biological ankle function during level ground walking.

PMID- 23555841
TI  - The paratenon contributes to scleraxis-expressing cells during patellar tendon
      healing.
AB  - The origin of cells that contribute to tendon healing, specifically extrinsic
      epitenon/paratenon cells vs. internal tendon fibroblasts, is still debated. The
      purpose of this study is to determine the location and phenotype of cells that
      contribute to healing of a central patellar tendon defect injury in the mouse.
      Normal adult patellar tendon consists of scleraxis-expressing (Scx) tendon
      fibroblasts situated among aligned collagen fibrils. The tendon body is
      surrounded by paratenon, which consists of a thin layer of cells that do not
      express Scx and collagen fibers oriented circumferentially around the tendon. At
      3 days following injury, the paratenon thickens as cells within the paratenon
      proliferate and begin producing tenascin-C and fibromodulin. These cells migrate
      toward the defect site and express scleraxis and smooth muscle actin alpha by day
      7. The thickened paratenon tissue eventually bridges the tendon defect by day 14.
      Similarly, cells within the periphery of the adjacent tendon struts express these
      markers and become disorganized. Cells within the defect region show increased
      expression of fibrillar collagens (Col1a1 and Col3a1) but decreased expression of
      tenogenic transcription factors (scleraxis and mohawk homeobox) and collagen
      assembly genes (fibromodulin and decorin). By contrast, early growth response 1
      and 2 are upregulated in these tissues along with tenascin-C. These results
      suggest that paratenon cells, which normally do not express Scx, respond to
      injury by turning on Scx and assembling matrix to bridge the defect. Future
      studies are needed to determine the signaling pathways that drive these cells and
      whether they are capable of producing a functional tendon matrix. Understanding
      this process may guide tissue engineering strategies in the future by stimulating
      these cells to improve tendon repair.

PMID- 23555843
TI  - Valproic acid inhibits the release of soluble CD40L induced by non-nucleoside
      reverse transcriptase inhibitors in human immunodeficiency virus infected
      individuals.
AB  - Despite the use of highly active antiretroviral therapies (HAART), a majority of
      Human Immunodeficiency Virus Type 1 (HIV) infected individuals continually
      develop HIV - Associated Neurocognitive Disorders (HAND), indicating that host
      inflammatory mediators, in addition to viral proteins, may be contributing to
      these disorders. Consistent with this notion, we have previously shown that
      levels of the inflammatory mediator soluble CD40 ligand (sCD40L) are elevated in
      the plasma and cerebrospinal fluid (CSF) of HIV infected, cognitively impaired
      individuals, and that excess sCD40L can contribute to blood brain barrier (BBB)
      permeability in vivo, thereby signifying the importance of this inflammatory
      mediator in the pathogenesis of HAND. Here we demonstrate that the non-nucleoside
      reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) induces the release of
      circulating sCD40L in both HIV infected individuals and in an in vitro suspension
      of washed human platelets, which are the main source of circulating sCD40L.
      Additionally, EFV was found to activate glycogen synthase kinase 3 beta
      (GSK3beta) in platelets, and we now show that valproic acid (VPA), a known
      GSK3beta inhibitor, was able to attenuate the release of sCD40L in HIV infected
      individuals receiving EFV, and in isolated human platelets. Collectively these
      results have important implications in determining the pro-inflammatory role that
      some antiretroviral regimens may have. The use of antiretrovirals remains the
      best strategy to prevent HIV-associated illnesses, including HAND, however these
      drugs have clear limitations to this end, and thus, these results underscore the
      need to develop adjunctive therapies for HAND that can also minimize the
      undesired negative effects of the antiretrovirals.

PMID- 23555842
TI  - E47 and Id1 interplay in epithelial-mesenchymal transition.
AB  - E12/E47 proteins (encoded by E2A gene) are members of the class I basic helix
      loop-helix (bHLH) transcription factors (also known as E proteins). E47 has been
      described as repressor of E-cadherin and inducer of epithelial-mesenchymal
      transition (EMT). We reported previously that EMT mediated by E47 in MDCK cells
      occurs with a concomitant overexpression of Id1 and Id3 proteins. Id proteins
      belong to class V of HLH factors that lack the basic domain; they dimerise with E
      proteins and prevent their DNA interaction, thus, acting as dominant negative of
      E proteins. Here, we show that E47 interacts with Id1 in E47 overexpressing MDCK
      cells that underwent a full EMT as well as in mesenchymal breast carcinoma and
      melanoma cell lines. By conducting chromatin immunoprecipitation assays we
      demonstrate that E47 binds directly to the endogenous E-cadherin promoter of
      mesenchymal MDCK-E47 cells in a complex devoid of Id1. Importantly, our data
      suggest that both E47 and Id1 are required to maintain the mesenchymal phenotype
      of MDCK-E47 cells. These data support the collaboration between E47 and Id1 in
      the maintenance of EMT by mechanisms independent of the dominant negative action
      of Id1 on E47 binding to E-cadherin promoter. Finally, the analysis of several N0
      breast tumour series indicates that the expression of E47 and ID1 is
      significantly associated with the basal-like phenotype supporting the biological
      significance of the present findings.

PMID- 23555844
TI  - Functional monoecy due to delayed anther dehiscence: a novel mechanism in
      Pseuduvaria mulgraveana (Annonaceae).
AB  - Unlike most genera in the early-divergent angiosperm family Annonaceae,
      Pseuduvaria exhibits a diversity of floral sex expression. Most species are
      structurally andromonoecious (or possibly androdioecious), although the
      hermaphroditic flowers have been inferred to be functionally pistillate, with
      sterile staminodes. Pseuduvaria presents an ideal model for investigating the
      evolution of floral sex in early-divergent angiosperms, although detailed
      empirical studies are currently lacking. The phenology and pollination ecology of
      the Australian endemic species Pseuduvaria mulgraveana are studied in detail,
      including evaluations of floral scent chemistry, pollen viability, and floral
      visitors. Results showed that the flowers are pollinated by small diurnal
      nitidulid beetles and are protogynous. Pollen from both hermaphroditic and
      staminate flowers are shown to be equally viable. The structurally hermaphroditic
      flowers are nevertheless functionally pistillate as anther dehiscence is delayed
      until after petal abscission and hence after the departure of pollinators. This
      mechanism to achieve functional unisexuality of flowers has not previously been
      reported in angiosperms. It is known that protogyny is widespread amongst early
      divergent angiosperms, including the Annonaceae, and is effective in preventing
      autogamy. Delayed anther dehiscence represents a further elaboration of this, and
      is effective in preventing geitonogamy since very few sexually mature flowers
      occur simultaneously in an individual. We highlight the necessity for field-based
      empirical interpretations of functional floral sex expression prior to
      evaluations of evolutionary processes.

PMID- 23555845
TI  - Differential regulation of matrix-metalloproteinases and their tissue inhibitors
      in patients with aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)
      are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier
      breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to
      play an important role during early brain injury and cerebral vasospasm after
      aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP
      9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with
      cerebral vasospasm (CVS). METHODS: Blood samples were collected in 20 SAH
      patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched
      volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent
      assay. Doppler sonographic CVS was defined as a mean blood flow velocity above
      120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6
      month follow-up neurological outcome was evaluated using the Glasgow Outcome
      Score and the modified Rankin Scale. RESULTS: MMP-9 was higher in SAH patients
      compared to healthy controls (p<0.001). Patients with CVS (n = 11) had elevated
      MMP-9 serum levels compared to patients without CVS (n = 9, p<0.05). Higher MMP-9
      was observed in the presence of cerebral ischemia associated with cerebral
      vasospasm (p<0.05). TIMP-1 was increased in patients with SAH on day 4 (p<0.05).
      There was an imbalance of the MMP-9/TIMP-1 ratio in favor of MMP-9 in SAH
      patients, in particular those with CVS (p<0.001). MMP-3 and TIMP-3 were
      significantly lower in SAH patients throughout day 4 and day 7, respectively
      (p<0.05). We did not find an association between MMP-, TIMP levels and
      neurological outcome after 6 months. CONCLUSIONS: MMP-3 and -9 are differentially
      regulated in SAH patients with both enzymes showing peak levels correlating with
      the development of CVS. The inhibitors TIMP-1 and -3 were low during the acute
      phase after SAH and increased later on which might suggest a preponderance of pro
      inflammatory mechanisms.

PMID- 23555847
TI  - Fish assemblages associated with natural and anthropogenically-modified habitats
      in a marine embayment: comparison of baited videos and opera-house traps.
AB  - Marine embayments and estuaries play an important role in the ecology and life
      history of many fish species. Cockburn Sound is one of a relative paucity of
      marine embayments on the west coast of Australia. Its sheltered waters and close
      proximity to a capital city have resulted in anthropogenic intrusion and
      extensive seascape modification. This study aimed to compare the sampling
      efficiencies of baited videos and fish traps in determining the relative
      abundance and diversity of temperate demersal fish species associated with
      naturally occurring (seagrass, limestone outcrops and soft sediment) and modified
      (rockwall and dredge channel) habitats in Cockburn Sound. Baited videos sampled a
      greater range of species in higher total and mean abundances than fish traps.
      This larger amount of data collected by baited videos allowed for greater
      discrimination of fish assemblages between habitats. The markedly higher
      diversity and abundances of fish associated with seagrass and limestone outcrops,
      and the fact that these habitats are very limited within Cockburn Sound, suggests
      they play an important role in the fish ecology of this embayment. Fish
      assemblages associated with modified habitats comprised a subset of species in
      lower abundances when compared to natural habitats with similar physical
      characteristics. This suggests modified habitats may not have provided the
      necessary resource requirements (e.g. shelter and/or diet) for some species,
      resulting in alterations to the natural trophic structure and interspecific
      interactions. Baited videos provided a more efficient and non-extractive method
      for comparing fish assemblages and habitat associations of smaller bodied species
      and juveniles in a turbid environment.

PMID- 23555846
TI  - Serum biomarker gMS-Classifier2: predicting conversion to clinically definite
      multiple sclerosis.
AB  - BACKGROUND: Anti-glycan antibodies can be found in autoimmune diseases. IgM
      against glycan P63 was identified in clinically isolated syndromes (CIS) and
      included in gMS-Classifier2, an algorithm designed with the aim of identifying
      patients at risk of a second demyelinating attack. OBJECTIVE: To determine the
      value of gMS-Classifier2 as an early and independent predictor of conversion to
      clinically definite multiple sclerosis (CDMS). METHODS: Data were prospectively
      acquired from a CIS cohort. gMS-Classifier2 was determined in patients first seen
      between 1995 and 2007 with >= two 200 uL serum aliquots (N = 249). The primary
      endpoint was time to conversion to CDMS at two years, the factor tested was gMS
      Classifier2 status (positive/negative) or units; other exploratory time points
      were 5 years and total time of follow-up. RESULTS: Seventy-five patients (30.1%)
      were gMS-Classifier2 positive. Conversion to CDMS occurred in 31/75 (41.3%) of
      positive and 45/174 (25.9%) of negative patients (p = 0.017) at two years. Median
      time to CDMS was 37.8 months (95% CI 10.4-65.3) for positive and 83.9 months (95%
      CI 57.5-110.5) for negative patients. gMS-Classifier2 status predicted conversion
      to CDMS within two years of follow-up (HR = 1.8, 95% CI 1.1-2.8; p = 0.014). gMS
      Classifier2 units were also independent predictors when tested with either
      Barkhof criteria and OCB (HR = 1.2, CI 1.0-1.5, p = 0.020) or with T2 lesions and
      OCB (HR = 1.3, CI 1.1-1.5, p = 0.008). Similar results were obtained at 5 years
      of follow-up. Discrimination measures showed a significant change in the area
      under the curve (DeltaAUC) when adding gMS-Classifier2 to a model with either
      Barkhof criteria (DeltaAUC 0.0415, p = 0.012) or number of T2 lesions (DeltaAUC
      0.0467, p = 0.009), but not when OCB were added to these models. CONCLUSIONS: gMS
      Classifier2 is an independent predictor of early conversion to CDMS and could be
      of clinical relevance, particularly in cases in which OCB are not available.

PMID- 23555848
TI  - Analysis of free online physician advice services.
AB  - BACKGROUND: Online Consumer Health websites are a major source of information for
      patients worldwide. We focus on another modality, online physician advice. We aim
      to evaluate and compare the freely available online expert physicians' advice in
      different countries, its scope and the type of content provided. SETTING: Using
      automated methods for information retrieval and analysis, we compared consumer
      health portals from the US, Canada, the UK and Israel
      (WebMD,NetDoctor,AskTheDoctor and BeOK). The evaluated content was generated
      between 2002 and 2011. RESULTS: We analyzed the different sites, looking at the
      distribution of questions in the various health topics, answer lengths and
      content type. Answers could be categorized into longer broad-educational answers
      versus shorter patient-specific ones, with different physicians having personal
      preferences as to answer type. The Israeli website BeOK, providing 10 times the
      number of answers than in the other three health portals, supplied answers that
      are shorter on average than in the other websites. Response times in these sites
      may be rapid with 32% of the WebMD answers and 64% of the BeOK answers provided
      in less than 24 hours. The voluntary contribution model used by BeOK and WebMD
      enables generation of large numbers of physician expert answers at low cost,
      providing 50,000 and 3,500 answers per year, respectively. CONCLUSIONS: Unlike
      health information in online databases or advice and support in patient-forums,
      online physician advice provides qualified specialists' responses directly
      relevant to the questions asked. Our analysis showed that high numbers of expert
      answers could be generated in a timely fashion using a voluntary model. The
      length of answers varied significantly between the internet sites. Longer answers
      were associated with educational content while short answers were associated with
      patient-specific content. Standard site-specific guidelines for expert answers
      will allow for more desirable content (educational content) or better throughput
      (patient-specific content).

PMID- 23555850
TI  - Neural control of gas exchange patterns in insects: locust density-dependent
      phases as a test case.
AB  - The adaptive significance of discontinuous gas exchange cycles (DGC) in insects
      is contentious. Based on observations of DGC occurrence in insects of typically
      large brain size and often socially-complex life history, and spontaneous DGC in
      decapitated insects, the neural hypothesis for the evolution of DGC was recently
      proposed. It posits that DGC is a non-adaptive consequence of adaptive down
      regulation of brain activity at rest, reverting ventilatory control to pattern
      generating circuits in the thoracic ganglia. In line with the predictions of this
      new hypothesis, we expected a higher likelihood of DGC in the gregarious phase of
      the desert locust (Schistocerca gregaria, Orthoptera), which is characterized by
      a larger brain size and increased sensory sensitivity compared with the solitary
      phase. Furthermore, surgical severing of the neural connections between head and
      thoracic ganglia was expected to increase DGC prevalence in both phases, and to
      eliminate phase-dependent variation in gas exchange patterns. Using flow-through
      respirometry, we measured metabolic rates and gas exchange patterns in locusts at
      30 degrees C. In contrast to the predictions of the neural hypothesis, we found
      no phase-dependent differences in DGC expression. Likewise, surgically severing
      the descending regulation of thoracic ventilatory control did not increase DGC
      prevalence in either phase. Moreover, connective-cut solitary locusts abandoned
      DGC altogether, and employed a typical continuous gas exchange pattern despite
      maintaining metabolic rate levels of controls. These results are not consistent
      with the predictions of the neural hypothesis for the evolution of DGC in
      insects, and instead suggest neural plasticity of ventilatory control.

PMID- 23555849
TI  - Critical role of non-muscle myosin light chain kinase in thrombin-induced
      endothelial cell inflammation and lung PMN infiltration.
AB  - The pathogenesis of acute lung injury (ALI) involves bidirectional cooperation
      and close interaction between inflammatory and coagulation pathways. A key
      molecule linking coagulation and inflammation is the procoagulant thrombin, a
      serine protease whose concentration is elevated in plasma and lavage fluids of
      patients with ALI and acute respiratory distress syndrome (ARDS). However, little
      is known about the mechanism by which thrombin contributes to lung inflammatory
      response. In this study, we developed a new mouse model that permits
      investigation of lung inflammation associated with intravascular coagulation.
      Using this mouse model and in vitro approaches, we addressed the role of non
      muscle myosin light chain kinase (nmMLCK) in thrombin-induced endothelial cell
      (EC) inflammation and lung neutrophil (PMN) infiltration. Our in vitro
      experiments revealed a key role of nmMLCK in ICAM-1 expression by its ability to
      control nuclear translocation and transcriptional capacity of RelA/p65 in EC.
      When subjected to intraperitoneal thrombin challenge, wild type mice showed a
      marked increase in lung PMN infiltration via expression of ICAM-1. However, these
      responses were markedly attenuated in mice deficient in nmMLCK. These results
      provide mechanistic insight into lung inflammatory response associated with
      intravascular coagulation and identify nmMLCK as a critical target for modulation
      of lung inflammation.

PMID- 23555851
TI  - New targets for drug discovery against malaria.
AB  - A mathematical model which predicts the intraerythrocytic stages of Plasmodium
      falciparum infection was developed using data from malaria-infected mice.
      Variables selected accounted for levels of healthy red blood cells, merozoite
      (Plasmodium asexual phase) infected red blood cells, gametocyte (Plasmodium
      sexual phase) infected red blood cells and a phenomenological variable which
      accounts for the mean activity of the immune system of the host. The model built
      was able to reproduce the behavior of three different scenarios of malaria. It
      predicts the later dynamics of malaria-infected humans well after the first peak
      of parasitemia, the qualitative response of malaria-infected monkeys to
      vaccination and the changes observed in malaria-infected mice when they are
      treated with antimalarial drugs. The mathematical model was used to identify new
      targets to be focused on drug design. Optimization methodologies were applied to
      identify five targets for minimizing the parasite load; four of the targets thus
      identified have never before been taken into account in drug design. The
      potential targets include: 1) increasing the death rate of the gametocytes, 2)
      decreasing the invasion rate of the red blood cells by the merozoites, 3)
      increasing the transformation of merozoites into gametocytes, 4) decreasing the
      activation of the immune system by the gametocytes, and finally 5) a combination
      of the previous target with decreasing the recycling rate of the red blood cells.
      The first target is already used in current therapies, whereas the remainders are
      proposals for potential new targets. Furthermore, the combined target (the
      simultaneous decrease of the activation of IS by gRBC and the decrease of the
      influence of IS on the recycling of hRBC) is interesting, since this combination
      does not affect the parasite directly. Thus, it is not expected to generate
      selective pressure on the parasites, which means that it would not produce
      resistance in Plasmodium.

PMID- 23555852
TI  - Spatiotemporal dynamics of high-gamma activities during a 3-stimulus visual
      oddball task.
AB  - Although many studies have investigated the neural basis of top-down and bottom
      up attention, it still requires refinement in both temporal and spatial terms. We
      used magnetoencephalography to investigate the spatiotemporal dynamics of high
      gamma (52-100 Hz) activities during top-down and bottom-up visual attentional
      processes, aiming to extend the findings from functional magnetic resonance
      imaging and event-related potential studies. Fourteen participants performed a 3
      stimulus visual oddball task, in which both infrequent non-target and target
      stimuli were presented. We identified high-gamma event-related synchronization in
      the left middle frontal gyrus, the left intraparietal sulcus, the left thalamus,
      and the visual areas in different time windows for the target and non-target
      conditions. We also found elevated imaginary coherence between the left
      intraparietal sulcus and the right middle frontal gyrus in the high-gamma band
      from 300 to 400 ms in the target condition, and between the left thalamus and the
      left middle frontal gyrus in theta band from 150 to 450 ms. In addition, the
      strength of high-gamma imaginary coherence between the left middle frontal gyrus
      and left intraparietal sulcus, between the left middle frontal gyrus and the
      right middle frontal gyrus, and the high-gamma power in the left thalamus
      predicted inter-subject variation in target detection response time. This source
      level electrophysiological evidence enriches our understanding of bi-directional
      attention processes: stimulus-driven bottom-up attention orientation to a
      salient, but irrelevant stimulus; and top-down allocation of attentional
      resources to stimulus evaluation.

PMID- 23555853
TI  - Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models
      of perturbed pregnancies.
AB  - Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules
      secreted by the placenta leads to the maternal hypertensive response
      characteristic of the pregnancy complication of preeclampsia. Structural
      abnormalities in the placenta have been proposed to result in altered placental
      perfusion, placental oxidative stress, cellular damage and inflammation and the
      release of anti-angiogenic compounds into the maternal circulation. The exact
      link between these factors is unclear. Here we show, using Magnetic Resonance
      Imaging as a tool to examine placental changes in mouse models of perturbed
      pregnancies, that T 2 contrast between distinct regions of the placenta is
      abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or
      transverse) relaxation times are explained as a consequence of hypoxia and
      acidosis within the tissue. Similar changes are observed in perturbed
      pregnancies, indicating that acidosis as well as hypoxia may be a feature of
      pregnancy complications such as preeclampsia and may play a prominent role in the
      signalling pathways that lead to the increased secretion of anti-angiogenic
      compounds.

PMID- 23555854
TI  - ERG induces epigenetic activation of Tudor domain-containing protein 1 (TDRD1) in
      ERG rearrangement-positive prostate cancer.
AB  - BACKGROUND: Overexpression of ERG transcription factor due to genomic ERG
      rearrangements defines a separate molecular subtype of prostate tumors. One of
      the consequences of ERG accumulation is modulation of the cell's gene expression
      profile. Tudor domain-containing protein 1 gene (TDRD1) was reported to be
      differentially expressed between TMPRSS2:ERG-negative and TMPRSS2:ERG-positive
      prostate cancer. The aim of our study was to provide a mechanistic explanation
      for the transcriptional activation of TDRD1 in ERG rearrangement-positive
      prostate tumors. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression measurements by
      real-time quantitative PCR revealed a remarkable co-expression of TDRD1 and ERG
      (r(2) = 0.77) but not ETV1 (r(2)<0.01) in human prostate cancer in vivo. DNA
      methylation analysis by MeDIP-Seq and bisulfite sequencing showed that TDRD1
      expression is inversely correlated with DNA methylation at the TDRD1 promoter in
      vitro and in vivo (rho = -0.57). Accordingly, demethylation of the TDRD1 promoter
      in TMPRSS2:ERG-negative prostate cancer cells by DNA methyltransferase inhibitors
      resulted in TDRD1 induction. By manipulation of ERG dosage through gene silencing
      and forced expression we show that ERG governs loss of DNA methylation at the
      TDRD1 promoter-associated CpG island, leading to TDRD1 overexpression.
      CONCLUSIONS/SIGNIFICANCE: We demonstrate that ERG is capable of disrupting a
      tissue-specific DNA methylation pattern at the TDRD1 promoter. As a result, TDRD1
      becomes transcriptionally activated in TMPRSS2:ERG-positive prostate cancer.
      Given the prevalence of ERG fusions, TDRD1 overexpression is a common alteration
      in human prostate cancer which may be exploited for diagnostic or therapeutic
      procedures.

PMID- 23555855
TI  - Putting brain training to the test in the workplace: a randomized, blinded,
      multisite, active-controlled trial.
AB  - BACKGROUND: Cognitive training (CT) is effective at improving cognitive outcomes
      in children with and without clinical impairment as well as older individuals.
      Yet whether CT is of any preventative health benefit to working age adults is
      controversial. Our objective was therefore to investigate the real-world efficacy
      of CT in the workplace, involving employees from across the working-age spectrum
      and addressing many of the design issues that have limited trials to date.
      METHODS AND FINDINGS: 135 white collar employees of a large Australian public
      sector organization were randomised to either 16 weeks (20 minutes three times
      per week) of online CT or an active control (AC) program of equal length and
      structure. Cognitive, wellbeing and productivity outcome measures were analysed
      across three timepoints: baseline, immediately after training and 6 months post
      training. CT effects on cognitive outcomes were limited, even after planned
      subgroup analyses of cognitive capacity and age. Unexpectedly, we found that our
      AC condition, which comprised viewing short documentaries about the natural
      world, had more impact. Compared to the CT group, 6 months after the end of
      training, those in the AC group experienced a significant increase in their self
      reported Quality of Life (Effect Size g = .34 vs -.15; TIME*GROUP p = .003),
      decrease in stress levels (g = .22 vs -.19; TIME x GROUP p = .03), and overall
      improvement in Psychological Wellbeing (g = .32 vs -.06; TIME*GROUP p = .02).
      CONCLUSIONS: CT does not appear to positively impact cognition or wellbeing
      amongst white collar office workers; however, short time-out respite activities
      may have value in the promotion of psychological wellbeing. Given looming
      challenges to workplace productivity, further work-based interventional research
      targeting employee mental health is recommended. TRIAL REGISTRATION: THIS TRIAL
      WAS REGISTERED WITH THE AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY:
      ACTRN12610000604000 (http://www.anzctr.org.au/TrialSearch.aspx).

PMID- 23555856
TI  - Evolutionary dynamics of microsatellite distribution in plants: insight from the
      comparison of sequenced brassica, Arabidopsis and other angiosperm species.
AB  - Despite their ubiquity and functional importance, microsatellites have been
      largely ignored in comparative genomics, mostly due to the lack of genomic
      information. In the current study, microsatellite distribution was characterized
      and compared in the whole genomes and both the coding and non-coding DNA
      sequences of the sequenced Brassica, Arabidopsis and other angiosperm species to
      investigate their evolutionary dynamics in plants. The variation in the
      microsatellite frequencies of these angiosperm species was much smaller than
      those for their microsatellite numbers and genome sizes, suggesting that
      microsatellite frequency may be relatively stable in plants. The microsatellite
      frequencies of these angiosperm species were significantly negatively correlated
      with both their genome sizes and transposable elements contents. The pattern of
      microsatellite distribution may differ according to the different genomic regions
      (such as coding and non-coding sequences). The observed differences in many
      important microsatellite characteristics (especially the distribution with
      respect to motif length, type and repeat number) of these angiosperm species were
      generally accordant with their phylogenetic distance, which suggested that the
      evolutionary dynamics of microsatellite distribution may be generally consistent
      with plant divergence/evolution. Importantly, by comparing these microsatellite
      characteristics (especially the distribution with respect to motif type) the
      angiosperm species (aside from a few species) all clustered into two obviously
      different groups that were largely represented by monocots and dicots, suggesting
      a complex and generally dichotomous evolutionary pattern of microsatellite
      distribution in angiosperms. Polyploidy may lead to a slight increase in
      microsatellite frequency in the coding sequences and a significant decrease in
      microsatellite frequency in the whole genome/non-coding sequences, but have
      little effect on the microsatellite distribution with respect to motif length,
      type and repeat number. Interestingly, several microsatellite characteristics
      seemed to be constant in plant evolution, which can be well explained by the
      general biological rules.

PMID- 23555858
TI  - Immune cells from SR/CR mice induce the regression of established tumors in
      BALB/c and C57BL/6 mice.
AB  - Few experimental models are available for the study of natural resistance to
      cancer. One of them is the SR/CR (spontaneous regression/complete resistance)
      mouse model in which natural resistance to a variety of cancer types appeared to
      be inherited in SR/CR strains of BALB/c and C57BL/6 mice. The genetic, cellular,
      and molecular effector mechanisms in this model are largely unknown, but cells
      from the innate immune system may play a significant role. In contrast to
      previous observations, the cancer resistance was limited to S180 sarcoma cancer
      cells. We were unable to confirm previous observations of resistance to EL-4
      lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer
      resistance against S180 sarcoma cells could be transferred to susceptible non
      resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+
      leukocytes and B-cells from SR/CR mice. In the responding recipient mice, the
      cancer disappeared gradually following infiltration of a large number of
      polymorphonuclear granulocytes and remarkably few lymphocytes in the remaining
      tumor tissues. This study confirmed that the in vivo growth and spread of cancer
      cells depend on a complex interplay between the cancer cells and the host
      organism. Here, hereditary components of the immune system, most likely the
      innate part, played a crucial role in this interplay and lead to resistance to a
      single experimental cancer type. The fact that leukocytes depleted of both
      CD4+/CD8+ and B cells from the cancer resistant donor mice could be transferred
      to inhibit S180 cancer cell growth in susceptible recipient mice support the
      vision of an efficient and adverse event free immunotherapy in future selected
      cancer types.

PMID- 23555857
TI  - Insulin-like growth factor 1 (IGF-1) enhances the protein expression of CFTR.
AB  - Low levels of insulin-like growth factor 1 (IGF-1) have been observed in the
      serum of cystic fibrosis (CF) patients. However, the effects of low serum IGF-1
      on the cystic fibrosis transmembrane conductance regulator (CFTR), whose
      defective function is the primary cause of cystic fibrosis, have not been
      studied. Here, we show in human cells that IGF-1 increases the steady-state
      levels of mature wildtype CFTR in a CFTR-associated ligand (CAL)- and TC10
      dependent manner; moreover, IGF-1 increases CFTR-mediated chloride transport.
      Using an acceptor photobleaching fluorescence resonance energy transfer (FRET)
      assay, we have confirmed the binding of CAL and CFTR in the Golgi. We also show
      that CAL overexpression inhibits forskolin-induced increases in the cell-surface
      expression of CFTR. We found that IGF-1 activates TC10, and active TC10 alters
      the functional association between CAL and CFTR. Furthermore, IGF-1 and active
      TC10 can reverse the CAL-mediated reduction in the cell-surface expression of
      CFTR. IGF-1 does not increase the expression of DeltaF508 CFTR, whose processing
      is arrested in the ER. This finding is consistent with our observation that IGF-1
      alters the functional interaction of CAL and CFTR in the Golgi. However, when
      DeltaF508 CFTR is rescued with low temperature or the corrector VRT-325 and
      proceeds to the Golgi, IGF-1 can increase the expression of the rescued DeltaF508
      CFTR. Our data support a model indicating that CAL-CFTR binding in the Golgi
      inhibits CFTR trafficking to the cell surface, leading CFTR to the degradation
      pathway instead. IGF-1-activated TC10 changes the interaction of CFTR and CAL,
      allowing CFTR to progress to the plasma membrane. These findings offer a
      potential strategy using a combinational treatment of IGF-1 and correctors to
      increase the post-Golgi expression of CFTR in cystic fibrosis patients bearing
      the DeltaF508 mutation.

PMID- 23555859
TI  - RNA-Seq analysis of Cocos nucifera: transcriptome sequencing and de novo assembly
      for subsequent functional genomics approaches.
AB  - BACKGROUND: Cocos nucifera (coconut), a member of the Arecaceae family, is an
      economically important woody palm grown in tropical regions. Despite its
      agronomic importance, previous germplasm assessment studies have relied solely on
      morphological and agronomical traits. Molecular biology techniques have been
      scarcely used in assessment of genetic resources and for improvement of important
      agronomic and quality traits in Cocos nucifera, mostly due to the absence of
      available sequence information. METHODOLOGY/PRINCIPAL FINDINGS: To provide basic
      information for molecular breeding and further molecular biological analysis in
      Cocos nucifera, we applied RNA-seq technology and de novo assembly to gain a
      global overview of the Cocos nucifera transcriptome from mixed tissue samples.
      Using Illumina sequencing, we obtained 54.9 million short reads and conducted de
      novo assembly to obtain 57,304 unigenes with an average length of 752 base pairs.
      Sequence comparison between assembled unigenes and released cDNA sequences of
      Cocos nucifera and Elaeis guineensis indicated that the assembled sequences were
      of high quality. Approximately 99.9% of unigenes were novel compared to the
      released coconut EST sequences. Using BLASTX, 68.2% of unigenes were successfully
      annotated based on the Genbank non-redundant (Nr) protein database. The annotated
      unigenes were then further classified using the Gene Ontology (GO), Clusters of
      Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      databases. CONCLUSIONS/SIGNIFICANCE: Our study provides a large quantity of novel
      genetic information for Cocos nucifera. This information will act as a valuable
      resource for further molecular genetic studies and breeding in coconut, as well
      as for isolation and characterization of functional genes involved in different
      biochemical pathways in this important tropical crop species.

PMID- 23555860
TI  - Non-canonical CRL4A/4B(CDT2) interacts with RAD18 to modulate post replication
      repair and cell survival.
AB  - The Cullin-4(CDT2) E3 ubiquitin ligase plays an essential role in DNA replication
      origin licensing directing degradation of several licensing factors at the G1/S
      transition in order to prevent DNA re-replication. Recently a RAD18-independent
      role of Cullin-4(CDT2) in PCNA monoubiquitylation has been proposed. In an effort
      to better understand the function of Cullin-4(CDT2) E3 ubiquitin ligase in
      mammalian Post-Replication Repair during an unperturbed S-phase, we show that
      down-regulation of Cullin-4(CDT2) leads to two distinguishable independent
      phenotypes in human cells that unveil at least two independent roles of Cullin
      4(CDT2) in S-phase. Apart from the re-replication preventing activity, we
      identified a non-canonical Cullin-4(CDT2) complex, containing both CUL4A and
      CUL4B, associated to the COP9 signalosome, that controls a RAD18-dependent damage
      avoidance pathway essential during an unperturbed S-phase. Indeed, we show that
      the non-canonical Cullin-4A/4B(CDT2) complex binds to RAD18 and it is required to
      modulate RAD18 protein levels onto chromatin and the consequent dynamics of PCNA
      monoubiquitylation during a normal S-phase. This function prevents replication
      stress, ATR hyper-signaling and, ultimately, apoptosis. A very similar PRR
      regulatory mechanism has been recently described for Spartan. Our findings
      uncover a finely regulated process in mammalian cells involving Post-Replication
      Repair factors, COP9 signalosome and a non-canonical Cullin4-based E3 ligase
      which is essential to tolerate spontaneous damage and for cell survival during
      physiological DNA replication.

PMID- 23555861
TI  - A differential effect of Indian ocean dipole and El Nino on cholera dynamics in
      Bangladesh.
AB  - BACKGROUND: A stationary (i.e., constant through time) association between El
      Nino Southern Oscillation (ENSO), the Indian Ocean Dipole (IOD) and epidemics of
      cholera in Bangladesh has been widely assumed. However, whether or not elements
      of the local climate that are relevant for cholera transmission have stationary
      signatures of the IOD on their dynamics over different time scales is still not
      clear. Here we report results on the time-varying relationships between the
      various remote and local environmental drivers and cholera incidence in
      Bangladesh. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross wavelet
      coherency analysis to examine patterns of association between monthly cholera
      cases in the hospitals in Dhaka and Matlab (1983-2008) and indices for both IOD
      and ENSO. Our results showed that the strength of both the IOD and ENSO
      associations with cholera hospitalizations changed across time scales during the
      study period. In Dhaka, 4-year long coherent cycles were observed between cholera
      and the index of IOD in 1988-1997. In Matlab, the effect of ENSO was more
      dominant while there was no evidence for an IOD effect on cholera
      hospitalizations. CONCLUSIONS/SIGNIFICANCE: Our results call for the
      consideration of non-stationary, possibly non-linear, patterns of association
      between cholera hospitalizations and climatic factors in cholera epidemic early
      warning systems.

PMID- 23555862
TI  - Relationships between clinicopathological features and cerebrospinal fluid
      biomarkers in Japanese patients with genetic prion diseases.
AB  - A national system for surveillance of prion diseases (PrDs) was established in
      Japan in April 1999. Here, we analyzed the relationships among prion protein gene
      (PRNP) mutations and the clinical features, cerebrospinal fluid (CSF) markers,
      and pathological characteristics of the major genotypes of genetic PrDs (gPrDs).
      We retrospectively analyzed age at onset and disease duration; the concentrations
      and incidences of 14-3-3 protein, tau protein, and abnormal prion protein
      (PrP(Sc)) in the CSF of 309 gPrD patients with P102L, P105L, E200K, V180I, or
      M232R mutations; and brain pathology in 32 autopsied patients. Three clinical
      phenotypes were seen: rapidly progressive Creutzfeldt-Jakob disease (CJD), which
      included 100% of E200K cases, 70% of M232R, and 21% of P102L; slowly progressive
      CJD, which included 100% of V180I and 30% of M232R; and Gerstmann-Straussler
      Scheinker disease, which included 100% of P105L and 79% of P102L. PrP(Sc) was
      detected in the CSF of more than 80% of patients with E200K, M232R, or P102L
      mutations but in only 39% of patients with V180I. V180I was accompanied by weak
      PrP immunoreactivity in the brain. Patients negative for PrP(Sc) in the CSF were
      older at disease onset than positive patients. Patients with mutations associated
      with high 14-3-3 protein levels in the CSF typically had synaptic deposition of
      PrP in the brain and a rapid course of disease. The presence of small PrP protein
      fragments in brain homogenates was not correlated with other clinicopathological
      features. Positivity for PrP(Sc) in the CSF may reflect the pathological process
      before or at disease onset, or abnormality in the secretion or metabolism of
      PrP(Sc). The amount of 14-3-3 protein in the CSF likely indicates the severity of
      the pathological process and accompanying neuronal damage. These characteristic
      features of the CSF in cases of gPrD will likely facilitate accurate diagnosis
      and clinicopathological study of the various disease subtypes.

PMID- 23555863
TI  - Prevention of contrast-induced acute kidney injury: is simple oral hydration
      similar to intravenous? A systematic review of the evidence.
AB  - BACKGROUND: Pre-procedural intravenous fluid administration is an effective
      prophylaxis measure for contrast-induced acute kidney injury. For logistical
      ease, the oral route is an alternative to the intravenous. The objective of this
      study was to compare the efficacy of the oral to the intravenous route in
      prevention of contrast-induced acute kidney injury. STUDY DESIGN: A systematic
      review and meta-analysis of randomised trials with a stratified analysis and
      metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE
      (1947 to week 47 2011), Cochrane CENTRAL (3(rd) quarter 2011). Two reviewers
      identified relevant trials and abstracted data. SETTINGS AND POPULATION: Trials
      including patients undergoing a contrast enhanced procedure. SELECTION CRITERIA:
      Randomised controlled trial; adult (>18 years) population; comparison of oral
      versus intravenous volume expansion. INTERVENTION: Oral route of volume expansion
      compared to the intravenous route. OUTCOMES: Any measure of acute kidney injury,
      need for renal replacement therapy, hospitalization and death. RESULTS: Six
      trials including 513 patients met inclusion criteria. The summary odds ratio was
      1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two
      routes of volume expansion. There was significant heterogeneity (Cochran's Q =
      11.65, p = 0.04; I(2) = 57). In the stratified analysis, inclusion of the five
      studies with a prespecified oral volume expansion protocol resulted in a shift
      towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also
      resolved the heterogeneity (Q = 3.19, P = 0.53; I(2) = 0). LIMITATIONS: Small
      number of studies identified; lack of hard clinical outcomes. CONCLUSION: The
      oral route may be as effective as the intravenous route for volume expansion for
      contrast-induced acute kidney injury prevention. Adequately powered trials with
      hard endpoints should be done given the potential advantages of oral (e.g.
      reduced patient burden and cost) over intravenous volume expansion.

PMID- 23555864
TI  - Calcification by reef-building sclerobionts.
AB  - It is widely accepted that deteriorating water quality associated with increased
      sediment stress has reduced calcification rates on coral reefs. However, there is
      limited information regarding the growth and development of reef building
      organisms, aside from the corals themselves. This study investigated encruster
      calcification on five fore-reefs in Tobago subjected to a range of sedimentation
      rates (1.2 to 15.9 mg cm(-2) d(-1)). Experimental substrates were used to assess
      rates of calcification in sclerobionts (e.g. crustose coralline algae, bryozoans
      and barnacles) across key reef microhabitats: cryptic (low-light), exposed (open
      horizontal) and vertical topographic settings. Sedimentation negatively impacted
      calcification by photosynthesising crustose coralline algae in exposed
      microhabitats and encrusting foram cover (%) in exposed and cryptic substrates.
      Heterotrophs were not affected by sedimentation. Fore-reef, turbid water
      encruster assemblages calcified at a mean rate of 757 (SD +/-317) g m(-2) y(-1).
      Different microhabitats were characterised by distinct calcareous encruster
      assemblages with different rates of calcification. Taxa with rapid lateral growth
      dominated areal cover but were not responsible for the majority of CaCO3
      production. Cryptobiont assemblages were composed of a suite of calcifying taxa
      which included sciaphilic cheilostome bryozoans and suspension feeding barnacles.
      These calcified at mean rates of 20.1 (SD +/-27) and 4.0 (SD +/-3.6) g m(-2) y(
      1) respectively. Encruster cover (%) on exposed and vertical substrates was
      dominated by crustose coralline algae which calcified at rates of 105.3 (SD +/
      67.7) g m(-2) y(-1) and 56.3 (SD +/-8.3) g m(-2) y(-1) respectively. Globally,
      encrusting organisms contribute significant amounts of carbonate to the reef
      framework. These results provide experimental evidence that calcification rates,
      and the importance of different encrusting organisms, vary significantly
      according to topography and sediment impacts. These findings also highlight the
      need for caution when modelling reef framework accretion and interpreting results
      which extrapolate information from limited data.

PMID- 23555866
TI  - A time-series analysis of the 20th century climate simulations produced for the
      IPCC's Fourth Assessment Report.
AB  - In this paper evidence of anthropogenic influence over the warming of the 20th
      century is presented and the debate regarding the time-series properties of
      global temperatures is addressed in depth. The 20th century global temperature
      simulations produced for the Intergovernmental Panel on Climate Change's Fourth
      Assessment Report and a set of the radiative forcing series used to drive them
      are analyzed using modern econometric techniques. Results show that both
      temperatures and radiative forcing series share similar time-series properties
      and a common nonlinear secular movement. This long-term co-movement is
      characterized by the existence of time-ordered breaks in the slope of their trend
      functions. The evidence presented in this paper suggests that while natural
      forcing factors may help explain the warming of the first part of the century,
      anthropogenic forcing has been its main driver since the 1970's. In terms of
      Article 2 of the United Nations Framework Convention on Climate Change,
      significant anthropogenic interference with the climate system has already
      occurred and the current climate models are capable of accurately simulating the
      response of the climate system, even if it consists in a rapid or abrupt change,
      to changes in external forcing factors. This paper presents a new methodological
      approach for conducting time-series based attribution studies.

PMID- 23555865
TI  - MicroRNA-21 is induced by rapamycin in a model of tuberous sclerosis (TSC) and
      lymphangioleiomyomatosis (LAM).
AB  - Lymphangioleiomyomatosis (LAM), a multisystem disease of women, is manifest by
      the proliferation of smooth muscle-like cells in the lung resulting in cystic
      lung destruction. Women with LAM can also develop renal angiomyolipomas. LAM is
      caused by mutations in the tuberous sclerosis complex genes (TSC1 or TSC2),
      resulting in hyperactive mammalian Target of Rapamycin (mTOR) signaling. The mTOR
      inhibitor, Rapamycin, stabilizes lung function in LAM and decreases the volume of
      renal angiomyolipomas, but lung function declines and angiomyolipomas regrow when
      treatment is discontinued, suggesting that factors induced by mTORC1 inhibition
      may promote the survival of TSC2-deficient cells. Whether microRNA (miRNA, miR)
      signaling is involved in the response of LAM to mTORC1 inhibition is unknown. We
      identified Rapamycin-dependent miRNA in LAM patient angiomyolipoma-derived cells
      using two separate screens. First, we assayed 132 miRNA of known significance to
      tumor biology. Using a cut-off of >1.5-fold change, 48 microRNA were Rapamycin
      induced, while 4 miRs were downregulated. In a second screen encompassing 946
      miRNA, 18 miRs were upregulated by Rapamycin, while eight were downregulated.
      Dysregulation of miRs 29b, 21, 24, 221, 106a and 199a were common to both
      platforms and were classified as candidate "RapamiRs." Validation by qRT-PCR
      confirmed that these microRNA were increased. miR-21, a pro-survival miR, was the
      most significantly increased by mTOR-inhibition (p<0.01). The regulation of miR
      21 by Rapamycin is cell type independent. mTOR inhibition promotes the processing
      of the miR-21 transcript (pri-miR-21) to a premature form (pre-miR-21). In
      conclusion, our findings demonstrate that Rapamycin upregulates multiple miRs,
      including pro-survival miRs, in TSC2-deficient patient-derived cells. The
      induction of miRs may contribute to the response of LAM and TSC patients to
      Rapamycin therapy.

PMID- 23555867
TI  - Targeting of beta adrenergic receptors results in therapeutic efficacy against
      models of hemangioendothelioma and angiosarcoma.
AB  - Therapeutic targeting of the beta-adrenergic receptors has recently shown
      remarkable efficacy in the treatment of benign vascular tumors such as infantile
      hemangiomas. As infantile hemangiomas are reported to express high levels of beta
      adrenergic receptors, we examined the expression of these receptors on more
      aggressive vascular tumors such as hemangioendotheliomas and angiosarcomas,
      revealing beta 1, 2, and 3 receptors were indeed present and therefore aggressive
      vascular tumors may similarly show increased susceptibility to the inhibitory
      effects of beta blockade. Using a panel of hemangioendothelioma and angiosarcoma
      cell lines, we demonstrate that beta adrenergic inhibition blocks cell
      proliferation and induces apoptosis in a dose dependent manner. Beta blockade is
      selective for vascular tumor cells over normal endothelial cells and
      synergistically effective when combined with standard chemotherapeutic or
      cytotoxic agents. We demonstrate that inhibition of beta adrenergic signaling
      induces large scale changes in the global gene expression patterns of vascular
      tumors, including alterations in the expression of established cell cycle and
      apoptotic regulators. Using in vivo tumor models we demonstrate that beta
      blockade shows remarkable efficacy as a single agent in reducing the growth of
      angiosarcoma tumors. In summary, these experiments demonstrate the selective
      cytotoxicity and tumor suppressive ability of beta adrenergic inhibition on
      malignant vascular tumors and have laid the groundwork for a promising treatment
      of angiosarcomas in humans.

PMID- 23555868
TI  - Treatment outcomes in undocumented Hispanic immigrants with HIV infection.
AB  - OBJECTIVE: Little is known about the treatment outcomes of undocumented Hispanic
      immigrants with HIV infection. We sought to compare the treatment outcomes of
      undocumented and documented patients 12-months after entering HIV care. METHODS:
      We conducted a retrospective cohort study of antiretroviral-naive patients 18
      years and older attending their first visit at Thomas Street Health Center in
      Houston, Texas, between 1/1/2003 and 6/30/2008. The study population of 1,620 HIV
      infected adults included 186 undocumented Hispanic, 278 documented Hispanic, 986
      Black, and 170 White patients. The main outcome measures were retention in care
      (quarter years with at least one completed HIV primary care provider visit) and
      HIV suppression (HIV RNA <400 copies/mL), both measured 12-months after entering
      HIV care. RESULTS: Undocumented Hispanic patients had lower median initial CD4
      cell count (132 cells/mm(3)) than documented Hispanic patients (166 cells/mm(3);
      P = 0.186), Black patients (226 cells/mm(3); P<0.001), and White patients (264
      cells/mm(3); P = 0.001). However, once in care, undocumented Hispanic patients
      did as well or better than their documented counterparts. One year after entering
      HIV care, undocumented Hispanics achieved similar rates of retention in care and
      HIV suppression as documented Hispanic and White patients. Of note, black
      patients were significantly less likely to have optimal retention in care
      (adjusted odds ratio [aOR] 0.65, CI = 0.45-0.94) or achieve HIV suppression (aOR
      0.32, CI = 0.17-0.61) than undocumented Hispanics. CONCLUSIONS: Undocumented
      Hispanic persons with HIV infection enter care with more advanced disease than
      documented persons, suggesting testing and/or linkage to care efforts for this
      difficult-to-reach population need intensification. Once diagnosed, however,
      undocumented Hispanics have outcomes as good as or better than other
      racial/ethnic groups. Safety net providers for undocumented immigrants are vital
      for maintaining individual and public health.

PMID- 23555869
TI  - Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor
      cells in mice.
AB  - Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been
      demonstrated to protect against ischemia-reperfusion injury in various organs. We
      investigated whether nicaraven can attenuate radiation-induced injury in
      hematopoietic stem/progenitor cells, which is the conmen complication of
      radiotherapy and one of the major causes of death in sub-acute phase after
      accidental exposure to high dose radiation. C57BL/6 mice were exposed to 1 Gy
      gamma-ray radiation daily for 5 days in succession (a total of 5 Gy), and given
      nicaraven or a placebo after each exposure. The mice were sacrificed 2 days after
      the last radiation treatment, and the protective effects and relevant mechanisms
      of nicaraven in hematopoietic stem/progenitor cells with radiation-induced damage
      were investigated by ex vivo examination. We found that post-radiation
      administration of nicaraven significantly increased the number, improved the
      colony-forming capacity, and decreased the DNA damage of hematopoietic
      stem/progenitor cells. The urinary levels of 8-oxo-2'-deoxyguanosine, a marker of
      DNA oxidation, were significantly lower in mice that were given nicaraven
      compared with those that received a placebo treatment, although the levels of
      intracellular and mitochondrial reactive oxygen species in the bone marrow cells
      did not differ significantly between the two groups. Interestingly, compared with
      the placebo treatment, the administration of nicaraven significantly decreased
      the levels of the inflammatory cytokines IL-6 and TNF-alpha in the plasma of
      mice. Our data suggest that nicaraven effectively diminished the effects of
      radiation-induced injury in hematopoietic stem/progenitor cells, which is likely
      associated with the anti-oxidative and anti-inflammatory properties of this
      compound.

PMID- 23555870
TI  - Transendothelial migration enables subsequent transmigration of neutrophils
      through underlying pericytes.
AB  - During acute inflammation, neutrophil recruitment into extravascular tissue
      requires neutrophil tethering and rolling on cytokine-activated endothelial cells
      (ECs), tight adhesion, crawling towards EC junctions and transendothelial
      migration (TEM). Following TEM, neutrophils must still traverse the
      subendothelial basement membrane and network of pericytes (PCs). Until recently,
      the contribution of the PC layer to neutrophil recruitment was largely ignored.
      Here we analyze human neutrophil interactions with interleukin (IL)-1beta
      activated human EC monolayers, PC monolayers and EC/PC bilayers in vitro.
      Compared to EC, PC support much lower levels of neutrophil binding (54.6% vs.
      7.1%, respectively) and transmigration (63.7 vs. 8.8%, respectively) despite
      comparable levels of IL-8 (CXCL8) synthesis and display. Remarkably, EC/PC
      bilayers support intermediate levels of transmigration (37.7%). Neutrophil
      adhesion to both cell types is Mac-1-dependent and while ICAM-1 transduction of
      PCs increases neutrophil adhesion to (41.4%), it does not increase transmigration
      through PC monolayers. TEM, which increases neutrophil Mac-1 surface expression,
      concomitantly increases the ability of neutrophils to traverse PCs (19.2%). These
      data indicate that contributions from both PCs and ECs must be considered in
      evaluation of microvasculature function in acute inflammation.

PMID- 23555871
TI  - Multiple interkingdom horizontal gene transfers in Pyrenophora and closely
      related species and their contributions to phytopathogenic lifestyles.
AB  - Many studies have reported horizontal gene transfer (HGT) events from eukaryotes,
      especially fungi. However, only a few investigations summarized multiple
      interkingdom HGTs involving important phytopathogenic species of Pyrenophora and
      few have investigated the genetic contributions of HGTs to fungi. We investigated
      HGT events in P. teres and P. tritici-repentis and discovered that both species
      harbored 14 HGT genes derived from bacteria and plants, including 12 HGT genes
      that occurred in both species. One gene coding a leucine-rich repeat protein was
      present in both species of Pyrenophora and it may have been transferred from a
      host plant. The transfer of genes from a host plant to pathogenic fungi has been
      reported rarely and we discovered the first evidence for this transfer in
      phytopathogenic Pyrenophora. Two HGTs in Pyrenophora underwent subsequent
      duplications. Some HGT genes had homologs in a few other fungi, indicating
      relatively ancient transfer events. Functional analyses indicated that half of
      the HGT genes encoded extracellular proteins and these may have facilitated the
      infection of plants by Pyrenophora via interference with plant defense-response
      and the degradation of plant cell walls. Some other HGT genes appeared to
      participate in carbohydrate metabolism. Together, these functions implied that
      HGTs may have led to highly efficient mechanisms of infection as well as the
      utilization of host carbohydrates. Evolutionary analyses indicated that HGT genes
      experienced amelioration, purifying selection, and accelerated evolution. These
      appeared to constitute adaptations to the background genome of the recipient. The
      discovery of multiple interkingdom HGTs in Pyrenophora, their significance to
      infection, and their adaptive evolution, provided valuable insights into the
      evolutionary significance of interkingdom HGTs from multiple donors.

PMID- 23555872
TI  - Evaluation of the INS-1 832/13 cell line as a beta-cell based screening system to
      assess pollutant effects on beta-cell function.
AB  - Environmental pollutants have recently emerged as potential risk factors for
      metabolic diseases, urging systematic investigation of pollutant effects on
      metabolic disease processes. To enable risk assessment of these so-called
      metabolic disruptors the use of stable, robust and well-defined cell based
      screening systems has recently been encouraged. Since beta-cell
      (dys)functionality is central in diabetes pathophysiology, the need to develop
      beta-cell based pollutant screening systems is evident. In this context, the
      present research evaluated the strengths and weaknesses of the INS-1 832/13
      pancreatic beta-cell line as diabetogenic pollutant screening system with a focus
      on beta-cell function. After optimization of exposure conditions, positive
      (exendin-4, glibenclamide) and negative (diazoxide) control compounds for acute
      insulin secretion responses were tested and those with the most profound effects
      were selected to allow potency estimations and ranking of pollutants. This was
      followed by a first explorative screening of acute bisphenol A and bis(2
      ethylhexyl)phthalate effects. The same approach was applied for chronic
      exposures, focusing primarily on evaluation of acknowledged chronic stimulators
      (diazoxide, T0901317, exendin-4) or inhibitors (glibenclamide) of insulin
      secretion responses to select the most responsive ones for use as control
      compounds in a chronic pollutant testing framework. Our results showed that INS-1
      832/13 cells responded conform previous observations regarding acute effects of
      control compounds on insulin secretion, while bisphenol A and bis(2
      ethylhexyl)phthalate had limited acute effects. Furthermore, chronic exposure to
      known beta-cell reactive compounds resulted in deviating insulin secretion and
      insulin content profiles compared to previous reports. In conclusion, this INS-1
      subclone appears to lack certain characteristics needed to respond appropriately
      to acute pollutant exposure or long term exposure to known beta-cell reactive
      compounds and thus seems to be, in our setting, inadequate as a diabetogenic
      pollutant screening system.

PMID- 23555873
TI  - Alpha-band rhythms in visual task performance: phase-locking by rhythmic sensory
      stimulation.
AB  - Oscillations are an important aspect of neuronal activity. Interestingly,
      oscillatory patterns are also observed in behaviour, such as in visual
      performance measures after the presentation of a brief sensory event in the
      visual or another modality. These oscillations in visual performance cycle at the
      typical frequencies of brain rhythms, suggesting that perception may be closely
      linked to brain oscillations. We here investigated this link for a prominent
      rhythm of the visual system (the alpha-rhythm, 8-12 Hz) by applying rhythmic
      visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance
      response in visual areas, and testing its effects on subsequent visual target
      discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has
      specific behavioral consequences, relative to stimulation at control frequencies
      (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual
      performance measures, that 3) correlate in precise frequency across individuals
      with resting alpha-rhythms recorded over parieto-occipital areas. The most
      parsimonious explanation for these three findings is entrainment (phase-locking)
      of ongoing perceptually relevant alpha-band brain oscillations by rhythmic
      sensory events. These findings are in line with occipital alpha-oscillations
      underlying periodicity in visual performance, and suggest that rhythmic
      stimulation at frequencies of intrinsic brain-rhythms can be used to reveal
      influences of these rhythms on task performance to study their functional roles.

PMID- 23555874
TI  - Association between soluble (Pro)renin receptor concentration in cord blood and
      small for gestational age birth: a cross-sectional study.
AB  - OBJECTIVE: The (pro)renin receptor [(P)RR] has been recognized as a
      multifunctional receptor. The purpose of this study was to assess the association
      between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e.,
      neonatal blood at birth) and small for gestational age (SGA) birth. METHODS:
      Participants were women with a singleton pregnancy who delivered at the National
      Center for Child Health and Development between January 2010 and December 2011.
      Inclusion criteria were availability of maternal pre-pregnancy and paternal body
      mass index, and the absence of structural anomalies in neonates. s(P)RR
      concentration in cord blood was measured in 621 neonates. The 621 pairs of
      mothers and neonates were categorized into four groups based on quartiles of
      s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the
      10(th) percentile for gestational age. Logistic regression analysis was performed
      to assess the association between cord plasma s(P)RR concentration (quartiles)
      and incidence of SGA births. RESULTS: Among 621 neonates, 55 (8.9%) were
      diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average
      s(P)RR concentration in cord blood was 66.1+/-12.6 ng/ml (mean+/-standard
      deviation). There were 155 pairs in the first plasma s(P)RR concentration
      quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2-65.1
      ng/ml), 157 pairs in the third quartile (Q3: 65.1-73.1 ng/ml) and 156 pairs in
      the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18
      (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4,
      respectively. The odds ratio of SGA births was 0.24 (95% confidence interval:
      0.08-0.71) for the fourth quartile compared to the first quartile in multivariate
      models. The P-value for trend was also significant (P = 0.020). CONCLUSION: High
      s(P)RR concentration is associated with a lower SGA birth likelihood.

PMID- 23555875
TI  - The chemotherapeutic agent DMXAA as a unique IRF3-dependent type-2 vaccine
      adjuvant.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent type I interferon (IFN)
      inducer, was evaluated as a chemotherapeutic agent in mouse cancer models and
      proved to be well tolerated in human cancer clinical trials. Despite its multiple
      biological functions, DMXAA has not been fully characterized for the potential
      application as a vaccine adjuvant. In this report, we show that DMXAA does act as
      an adjuvant due to its unique property as a soluble innate immune activator.
      Using OVA as a model antigen, DMXAA was demonstrated to improve on the antigen
      specific immune responses and induce a preferential Th2 (Type-2) response. The
      adjuvant effect was directly dependent on the IRF3-mediated production of type-I
      interferon, but not IL-33. DMXAA could also enhance the immunogenicity of
      influenza split vaccine which led to significant increase in protective responses
      against live influenza virus challenge in mice compared to split vaccine alone.
      We propose that DMXAA can be used as an adjuvant that targets a specific innate
      immune signaling pathway via IRF3 for potential applications including vaccines
      against influenza which requires a high safety profile.

PMID- 23555876
TI  - Dynamics of vocalization-induced modulation of auditory cortical activity at mid
      utterance.
AB  - BACKGROUND: Recent research has addressed the suppression of cortical sensory
      responses to altered auditory feedback that occurs at utterance onset regarding
      speech. However, there is reason to assume that the mechanisms underlying
      sensorimotor processing at mid-utterance are different than those involved in
      sensorimotor control at utterance onset. The present study attempted to examine
      the dynamics of event-related potentials (ERPs) to different acoustic versions of
      auditory feedback at mid-utterance. METHODOLOGY/PRINCIPAL FINDINGS: Subjects
      produced a vowel sound while hearing their pitch-shifted voice (100 cents), a sum
      of their vocalization and pure tones, or a sum of their vocalization and white
      noise at mid-utterance via headphones. Subjects also passively listened to
      playback of what they heard during active vocalization. Cortical ERPs were
      recorded in response to different acoustic versions of feedback changes during
      both active vocalization and passive listening. The results showed that, relative
      to passive listening, active vocalization yielded enhanced P2 responses to the
      100 cents pitch shifts, whereas suppression effects of P2 responses were observed
      when voice auditory feedback was distorted by pure tones or white noise.
      CONCLUSION/SIGNIFICANCE: The present findings, for the first time, demonstrate a
      dynamic modulation of cortical activity as a function of the quality of acoustic
      feedback at mid-utterance, suggesting that auditory cortical responses can be
      enhanced or suppressed to distinguish self-produced speech from externally
      produced sounds.

PMID- 23555877
TI  - Antifungal efficacy during Candida krusei infection in non-conventional models
      correlates with the yeast in vitro susceptibility profile.
AB  - The incidence of opportunistic fungal infections has increased in recent decades
      due to the growing proportion of immunocompromised patients in our society.
      Candida krusei has been described as a causative agent of disseminated fungal
      infections in susceptible patients. Although its prevalence remains low among
      yeast infections (2-5%), its intrinsic resistance to fluconazole makes this yeast
      important from epidemiologic aspects. Non mammalian organisms are feasible models
      to study fungal virulence and drug efficacy. In this work we have used the
      lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as
      models to assess antifungal efficacy during infection by C. krusei. This yeast
      killed G. mellonella at 25, 30 and 37 degrees C and reduced haemocytic density.
      Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect
      against C. krusei infection, in contrast to amphotericin B, voriconazole or
      caspofungin. However, the doses of these antifungals required to obtain larvae
      protection were always higher during C. krusei infection than during C. albicans
      infection. Similar results were found in the model host C. elegans. Our work
      demonstrates that non mammalian models are useful tools to investigate in vivo
      antifungal efficacy and virulence of C. krusei.

PMID- 23555878
TI  - Interferon-lambda3 (IFN-lambda3) and its cognate receptor subunits in tree shrews
      (Tupaia belangeri): genomic sequence retrieval, molecular identification and
      expression analysis.
AB  - Type III IFNs (IFN-lambdas) constitute a new subfamily with antiviral activities
      by signaling through a unique receptor complex composed of IFN-lambdas receptor 1
      (IFNlambdaR1) and interleukin-10 receptor 2 (IL10R2). As tree shrews (Tupaia
      belangeri) have shown susceptiblility to several human viruses, they are a
      potentially important model for analyzing viral infection. However, little is
      known about their IFN-lambdas system. We used the tree shrew genome to retrieve
      IFN-lambdas and their receptor contig sequences by BLASTN and BLASTZ algorithms,
      and GenScan was used to scan transcripts from the putative contig sequences. RT
      PCR and bioinformatic methods were then used to clone and characterize the IFN
      lambdas system. Due to its highest identity with human IFN-lambda3, we opted to
      define one intact IFN-lambda gene, tsIFN-lambda3, as well as its two receptor
      subunits, tsIFNlambdaR1 and tsIL10R2. Additionally, our results showed that tsIFN
      lambda3 contained many features conserved in IFN-lambda3 genes from other
      mammals, including conserved signal peptide cleavage and glycosylation sites, and
      several residues responsible for binding to the type III IFNR. We also found six
      transcript variants in the receptors: three in tsIFNlambdaR1, wherein different
      extracellular regions exist in three transmembrane proteins, resulting in
      different affinities with IFN-lambdas; and three more variants in tsIL10R2,
      encoding one transmembrane and two soluble proteins. Based on tissue distribution
      in the liver, heart, brain, lung, intestine, kidney, spleen, and stomach, we
      found that IFN-lambdas receptor complex was expressed in a variety of organs
      although the expression level differed markedly between them. As the first study
      to find transcript variants in IL-10R2, our study offers novel insights that may
      have important implications for the role of IFN-lambdas in tree shrews'
      susceptibility with a variety of human viruses, bolstering the arguments for
      using tree shrews as an animal model in the study of human viral infections.

PMID- 23555879
TI  - Tracking transplanted bone marrow stem cells and their effects in the rat MCAO
      stroke model.
AB  - In this study, rat bone marrow stromal stem cells (BMSCs) were tracked after IV
      administration to rats with experimental stroke caused by middle cerebral artery
      occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell
      composition, brain glia and sensorimotor behavior was studied and compared to
      that which occurred spontaneously during the normal recovery process after
      stroke. We found that the vast majority of radiolabeled or fluorescently labeled
      BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) 3 days
      after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced
      rapid alterations in host blood cell composition, increasing both neutrophil and
      total white blood cell count by 6 hours post-injection. In contrast, few injected
      BMSCs traveled to the brain and almost none endured there long term. Nonetheless,
      BMSC treatment produced dramatic changes in the number and activation of brain
      astroglia and microglia, particularly in the region of the infarct. These
      cellular changes were correlated with a marked improvement in performance on
      tests of sensory and motor function as compared to the partial recovery of
      function seen in PBS-injected control rats. We conclude that the notable recovery
      in function observed after systemic administration of BMSCs to MCAO rats is
      likely due to the cellular changes in blood and/or brain cell number, activation
      state and their cytokine/growth factor products.

PMID- 23555881
TI  - Effects of nanostructures and mouse embryonic stem cells on in vitro
      morphogenesis of rat testicular cords.
AB  - Morphogenesis of tubular structures is a common event during embryonic
      development. The signals providing cells with topographical cues to define a cord
      axis and to form new compartments surrounded by a basement membrane are poorly
      understood. Male gonadal differentiation is a late event during organogenesis and
      continues into postnatal life. The cellular changes resemble the mechanisms
      during embryonic life leading to tubular structures in other organs. Testicular
      cord formation is dependent on and first recognized by SRY-dependent aggregation
      of Sertoli cells leading to the appearance of testis-specific cord-like
      structures. Here we explored whether testicular cells use topographical cues in
      the form of nanostructures to direct or stimulate cord formation and whether
      embryonic stem cells (ES) or soluble factors released from those cells have an
      impact on this process. Using primary cell cultures of immature rats we first
      revealed that variable nanogratings exerted effects on peritubular cells and on
      Sertoli cells (at less than <1000 cells/mm(2)) by aligning the cell bodies
      towards the direction of the nanogratings. After two weeks of culture testicular
      cells assembled into a network of cord-like structures. We revealed that Sertoli
      cells actively migrate towards existing clusters. Contractions of peritubular
      cells lead to the transformation of isolated clusters into cord-like structures.
      The addition of mouse ES cells or conditioned medium from ES cells accelerated
      this process. Our studies show that epithelial (Sertoli cell) and mesenchymal
      (peritubular cells) cells crosstalk and orchestrate the formation of cords in
      response to physical features of the underlying matrix as well as secretory
      factors from ES cells. We consider these data on testicular morphogenesis
      relevant for the better understanding of mechanisms in cord formation also in
      other organs which may help to create optimized in vitro tools for artificial
      organogenesis.

PMID- 23555880
TI  - FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt
      signaling in solid tumors.
AB  - BACKGROUND: The forkhead box transcription factor FOXQ1 has been shown to be
      upregulated in colorectal cancer (CRC) and metastatic breast cancer and involved
      in tumor development, epithelial-mesenchymal transition and chemoresistance. Yet,
      its transcriptional regulation is still unknown. METHODS: FOXQ1 mRNA and protein
      expression were analysed in a panel of CRC cell lines, and laser micro-dissected
      human biopsy samples by qRT-PCR, microarray GeneChip(r) U133 Plus 2.0 and western
      blots. FOXQ1 regulation was assayed by chromatin immunoprecipitation and
      luciferase reporter assays. RESULTS: FOXQ1 was robustly induced in CRC compared
      to other tumors, but had no predictive value with regards to grade, metastasis
      and survival in CRC. Prototype-based gene coexpression and gene set enrichment
      analysis showed a significant association between FOXQ1 and the Wnt pathway in
      tumors and cancer cell lines from different tissues. In vitro experiments
      confirmed, on a molecular level, FOXQ1 as a direct Wnt target. Analysis of known
      Wnt targets identified FOXQ1 as the most suitable marker for canonical Wnt
      activation across a wide panel of cell lines derived from different tissues.
      CONCLUSIONS: Our data show that FOXQ1 is one of the most over-expressed genes in
      CRC and a direct target of the canonical Wnt pathway. It is a potential new
      marker for detection of early CRC and Wnt activation in tumors of different
      origins.

PMID- 23555882
TI  - MultiPSQ: a software solution for the analysis of diagnostic n-plexed
      pyrosequencing reactions.
AB  - BACKGROUND: Pyrosequencing can be applied for Single-Nucleotide-Polymorphism
      (SNP)-based pathogen typing or for providing sequence information of short DNA
      stretches. However, for some pathogens molecular typing cannot be performed
      relying on a single SNP or short sequence stretch, necessitating the
      consideration of several genomic regions. A promising rapid approach is the
      simultaneous application of multiple sequencing primers, called multiplex
      pyrosequencing. These primers generate a fingerprint-pyrogram which is
      constituted by the sum of all individual pyrograms originating from each primer
      used. METHODS: To improve pyrosequencing-based pathogen typing, we have developed
      the software tool MultiPSQ that expedites the analysis and evaluation of
      multiplex-pyrograms. As a proof of concept, a multiplex pyrosequencing assay for
      the typing of orthopoxviruses was developed to analyse clinical samples diagnosed
      in the German Consultant Laboratory for Poxviruses. RESULTS: The software tool
      MultiPSQ enabled the analysis of multiplex-pyrograms originating from various
      pyrosequencing primers. Thus several target regions can be used for pathogen
      typing based on pyrosequencing. As shown with a proof of concept assay, SNPs
      present in different orthopoxvirus strains could be identified correctly with two
      primers by MultiPSQ. CONCLUSIONS: Software currently available is restricted to a
      fixed number of SNPs and sequencing primers, severely limiting the usefulness of
      this technique. In contrast, our novel software MultiPSQ allows analysis of data
      from multiplex pyrosequencing assays that contain any number of sequencing
      primers covering any number of polymorphisms.

PMID- 23555883
TI  - Low cost extraction and isothermal amplification of DNA for infectious diarrhea
      diagnosis.
AB  - In order to counter the common perception that molecular diagnostics are too
      complicated to work in low resource settings, we have performed a difficult
      sample preparation and DNA amplification protocol using instrumentation designed
      to be operated without wall or battery power. In this work we have combined a
      nearly electricity-free nucleic acid extraction process with an electricity-free
      isothermal amplification assay to detect the presence of Clostridium difficile
      (C. difficile) DNA in the stool of infected patients. We used helicase-dependent
      isothermal amplification (HDA) to amplify the DNA in a low-cost, thermoplastic
      reaction chip heated with a pair of commercially available toe warmers, while
      using a simple Styrofoam insulator. DNA was extracted from known positive and
      negative stool samples. The DNA extraction protocol utilized an air pressure
      driven solid phase extraction device run using a standard bicycle pump. The
      simple heater setup required no electricity or battery and was capable of
      maintaining the temperature at 65 degrees C+/-2 degrees C for 55 min, suitable
      for repeatable HDA amplification. Experiments were performed to explore the
      adaptability of the system for use in a range of ambient conditions. When
      compared to a traditional centrifuge extraction protocol and a laboratory
      thermocycler, this disposable, no power platform achieved approximately the same
      lower limit of detection (1.25*10(-2) pg of C. difficile DNA) while requiring
      much less raw material and a fraction of the lab infrastructure and cost. This
      proof of concept study could greatly impact the accessibility of molecular assays
      for applications in global health.

PMID- 23555885
TI  - Human mobility in a continuum approach.
AB  - Human mobility is investigated using a continuum approach that allows to
      calculate the probability to observe a trip to any arbitrary region, and the
      fluxes between any two regions. The considered description offers a general and
      unified framework, in which previously proposed mobility models like the gravity
      model, the intervening opportunities model, and the recently introduced radiation
      model are naturally resulting as special cases. A new form of radiation model is
      derived and its validity is investigated using observational data offered by
      commuting trips obtained from the United States census data set, and the mobility
      fluxes extracted from mobile phone data collected in a western European country.
      The new modeling paradigm offered by this description suggests that the complex
      topological features observed in large mobility and transportation networks may
      be the result of a simple stochastic process taking place on an inhomogeneous
      landscape.

PMID- 23555884
TI  - Modulations of EEG beta power during planning and execution of grasping
      movements.
AB  - Although beta oscillations (~ 13-35 Hz) are often considered as a sensorimotor
      rhythm, their functional role remains debated. In particular, the modulations of
      beta power during preparation and execution of complex movements in different
      contexts were barely investigated. Here, we analysed the beta oscillations
      recorded with electroencephalography (EEG) in a precued grasping task in which we
      manipulated two critical parameters: the grip type (precision vs. side grip) and
      the force (high vs. low force) required to pull an object along a horizontal
      axis. A cue was presented 3 s before a GO signal and provided full, partial or no
      information about the two movement parameters. We measured beta power over the
      centro-parietal areas during movement preparation and execution as well as during
      object hold. We explored the modulations of power in relation to the amount and
      type of prior information provided by the cue. We also investigated how beta
      power was affected by the grip and force parameters. We observed an increase in
      beta power around the cue onset followed by a decrease during movement
      preparation and execution. These modulations were followed by a transient power
      increase during object hold. This pattern of modulations did not differ between
      the 4 movement types (2 grips *2 forces). However, the amount and type of prior
      information provided by the cue had a significant effect on the beta power during
      the preparatory delay. We discuss how these results fit with current hypotheses
      on the functional role of beta oscillations.

PMID- 23555886
TI  - Real-time continuous glucose monitoring shows high accuracy within 6 hours after
      sensor calibration: a prospective study.
AB  - Accurate and timely glucose monitoring is essential in intensive care units. Real
      time continuous glucose monitoring system (CGMS) has been advocated for many
      years to improve glycemic management in critically ill patients. In order to
      determine the effect of calibration time on the accuracy of CGMS, real-time
      subcutaneous CGMS was used in 18 critically ill patients. CGMS sensor was
      calibrated with blood glucose measurements by blood gas/glucose analyzer every 12
      hours. Venous blood was sampled every 2 to 4 hours, and glucose concentration was
      measured by standard central laboratory device (CLD) and by blood gas/glucose
      analyzer. With CLD measurement as reference, relative absolute difference (mean+/
      SD) in CGMS and blood gas/glucose analyzer were 14.4%+/-12.2% and 6.5%+/-6.2%,
      respectively. The percentage of matched points in Clarke error grid zone A was
      74.8% in CGMS, and 98.4% in blood gas/glucose analyzer. The relative absolute
      difference of CGMS obtained within 6 hours after sensor calibration (8.8%+/-7.2%)
      was significantly less than that between 6 to 12 hours after calibration (20.1%+/
      13.5%, p<0.0001). The percentage of matched points in Clarke error grid zone A
      was also significantly higher in data sets within 6 hours after calibration
      (92.4% versus 57.1%, p<0.0001). In conclusion, real-time subcutaneous CGMS is
      accurate in glucose monitoring in critically ill patients. CGMS sensor should be
      calibrated less than 6 hours, no matter what time interval recommended by
      manufacturer.

PMID- 23555887
TI  - C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink
      repair and interacts with a RAD51C homolog.
AB  - The Fanconi anemia (FA) pathway recognizes interstrand DNA crosslinks (ICLs) and
      contributes to their conversion into double-strand DNA breaks, which can be
      repaired by homologous recombination. Seven orthologs of the 15 proteins
      associated with Fanconi anemia are functionally conserved in the model organism
      C. elegans. Here we report that RNF-113, a ubiquitin ligase, is required for RAD
      51 focus formation after inducing ICLs in C. elegans. However, the formation of
      foci of RPA-1 or FCD-2/FANCD2 in the FA pathway was not affected by depletion of
      RNF-113. Nevertheless, the RPA-1 foci formed did not disappear with time in the
      depleted worms, implying serious defects in ICL repair. As a result, RNF-113
      depletion increased embryonic lethality after ICL treatment in wild-type worms,
      but it did not increase the ICL-induced lethality of rfs-1/rad51C mutants. In
      addition, the persistence of RPA-1 foci was suppressed in doubly-deficient rnf
      113;rfs-1 worms, suggesting that there is an epistatic interaction between the
      two genes. These results lead us to suggest that RNF-113 and RFS-1 interact to
      promote the displacement of RPA-1 by RAD-51 on single-stranded DNA derived from
      ICLs.

PMID- 23555888
TI  - Structural analysis of a novel cyclohexylamine oxidase from Brevibacterium
      oxydans IH-35A.
AB  - Cyclohexylamine oxidase (CHAO) is a flavoprotein first described in
      Brevibacterium oxydans strain IH-35A that carries out the initial step of the
      degradation of the industrial chemical cyclohexylamine to cyclohexanone. We have
      cloned and expressed in Escherichia coli the CHAO-encoding gene (chaA) from B.
      oxydans, purified CHAO and determined the structures of both the holoenzyme form
      of the enzyme and a product complex with cyclohexanone. CHAO is a 50 kDa monomer
      with a PHBH fold topology. It belongs to the flavin monooxygenase family of
      enzymes and exhibits high substrate specificity for alicyclic amines and sec
      alkylamines. The overall structure is similar to that of other members of the
      flavin monooxygenase family, but lacks either of the C- or N-terminal extensions
      observed in these enzymes. Active site features of the flavin monooxygenase
      family are conserved in CHAO, including the characteristic aromatic cage.
      Differences in the orientations of residues of the CHAO aromatic cage result in a
      substrate-binding site that is more open than those of its structural relatives.
      Since CHAO has a buried hydrophobic active site with no obvious route for
      substrates and products, a random acceleration molecular dynamics simulation has
      been used to identify a potential egress route. The path identified includes an
      intermediate cavity and requires transient conformation changes in a shielding
      loop and a residue at the border of the substrate-binding cavity. These results
      provide a foundation for further studies with CHAO aimed at identifying features
      determining substrate specificity and for developing the biocatalytic potential
      of this enzyme.

PMID- 23555889
TI  - Anti-cancer efficacy of silybin derivatives -- a structure-activity relationship.
AB  - Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of
      the popular dietary supplements and has been extensively studied for its
      antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that
      potency of silybin could be further enhanced through suitable modification/s in
      its chemical structure. Accordingly, here, we synthesized and characterized a
      series of silybin derivatives namely 2,3-dehydrosilybin (DHS), 7-O-methylsilybin
      (7OM), 7-O-galloylsilybin (7OG), 7,23-disulphatesilybin (DSS), 7-O
      palmitoylsilybin (7OP), and 23-O-palmitoylsilybin (23OP); and compared their anti
      cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate
      carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated
      better growth inhibitory effects and compared to silybin, while other silybin
      derivatives showed lesser or no efficacy. Next, we prepared the optical isomers
      (A and B) of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy.
      Isomers of these three silybin derivatives also showed better efficacy compared
      with respective silybin isomers, but in each, there was no clear cut silybin A
      versus B isomer activity preference. Further studies in HTB cells found that DHS,
      7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in
      HTB9 cells further confirmed that both the racemic mixtures as well as pure
      optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall,
      these results clearly suggest that the anti-cancer efficacy of silybin could be
      significantly enhanced through structural modifications, and identify strong anti
      cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that
      their efficacy and toxicity should be evaluated in relevant pre-clinical cancer
      models in rodents.

PMID- 23555890
TI  - Inhibition of SypG-induced biofilms and host colonization by the negative
      regulator SypE in Vibrio fischeri.
AB  - Vibrio fischeri produces a specific biofilm to promote colonization of its
      eukaryotic host, the squid Euprymna scolopes. Formation of this biofilm is
      induced by the sensor kinase RscS, which functions upstream of the response
      regulator SypG to regulate transcription of the symbiosis polysaccharide (syp)
      locus. Biofilm formation is also controlled by SypE, a multi-domain response
      regulator that consists of a central regulatory receiver (REC) domain flanked by
      an N-terminal serine kinase domain and a C-terminal serine phosphatase domain.
      SypE permits biofilm formation under rscS overexpression conditions, but inhibits
      biofilms induced by overexpression of sypG. We previously investigated the
      function of SypE in controlling biofilm formation induced by RscS. Here, we
      examined the molecular mechanism by which SypE naturally inhibits SypG-induced
      biofilms. We found that SypE's N-terminal kinase domain was both required and
      sufficient to inhibit SypG-induced biofilms. This effect did not occur at the
      level of syp transcription. Instead, under sypG-overexpressing conditions, SypE
      inhibited biofilms by promoting the phosphorylation of another syp regulator,
      SypA, a putative anti-sigma factor antagonist. Inhibition by SypE of SypG-induced
      biofilm formation could be overcome by the expression of a non-phosphorylatable
      SypA mutant, indicating that SypE functions primarily if not exclusively to
      control SypA activity via phosphorylation. Finally, the presence of SypE was
      detrimental to colonization under sypG-overexpressing conditions, as cells
      deleted for sypE outcompeted wild-type cells for colonization when both strains
      overexpressed sypG. These results provide further evidence that biofilm formation
      is critical to symbiotic colonization, and support a model in which SypE
      naturally functions to restrict biofilm formation, and thus host colonization, to
      the appropriate environmental conditions.

PMID- 23555891
TI  - Imperfect duplicate insertions type of mutations in plasmepsin V modulates
      binding properties of PEXEL motifs of export proteins in Indian Plasmodium vivax.
AB  - INTRODUCTION: Plasmepsin V (PM-V) have functionally conserved orthologues across
      the Plasmodium genus who's binding and antigenic processing at the PEXEL motifs
      for export about 200-300 essential proteins is important for the virulence and
      viability of the causative Plasmodium species. This study was undertaken to
      determine P. vivax plasmepsin V Ind (PvPM-V-Ind) PEXEL motif export pathway for
      pathogenicity-related proteins/antigens export thereby altering plasmodium
      exportome during erythrocytic stages. METHOD: We identify and characterize
      Plasmodium vivax plasmepsin-V-Ind (mutant) gene by cloning, sequence analysis, in
      silico bioinformatic protocols and structural modeling predictions based on
      docking studies on binding capacity with PEXEL motifs processing in terms of
      binding and accessibility of export proteins. RESULTS: Cloning and sequence
      analysis for genetic diversity demonstrates PvPM-V-Ind (mutant) gene is highly
      conserved among all isolates from different geographical regions of India.
      Imperfect duplicate insertion types of mutations (SVSE from 246-249 AA and SLSE
      from 266-269 AA) were identified among all Indian isolates in comparison to
      P.vivax Sal-1 (PvPM-V-Sal 1) isolate. In silico bioinformatics interaction
      studies of PEXEL peptide and active enzyme reveal that PvPM-V-Ind (mutant) is
      only active in endoplasmic reticulum lumen and membrane embedding is essential
      for activation of plasmepsin V. Structural modeling predictions based on docking
      studies with PEXEL motif show significant variation in substrate protein binding
      of these imperfect mutations with data mined PEXEL sequences. The predicted
      variation in the docking score and interacting amino acids of PvPM-V-Ind (mutant)
      proteins with PEXEL and lopinavir suggests a modulation in the activity of PvPM-V
      in terms of binding and accessibility at these sites. CONCLUSION/SIGNIFICANCE:
      Our functional modeled validation of PvPM-V-Ind (mutant) imperfect duplicate
      insertions with data mined PEXEL sequences leading to altered binding and
      substrate accessibility of the enzyme makes it a plausible target to investigate
      export mechanisms for in silico virtual screening and novel pharmacophore
      designing.

PMID- 23555892
TI  - A polymorphism (rs2295080) in mTOR promoter region and its association with
      gastric cancer in a Chinese population.
AB  - BACKGROUND: As an imperative part of PI3K/Akt/mTOR pathway, mammalian target of
      rapamycin (mTOR) has been demonstrated to increase in gastric cancer cells and
      tumors. Our research explored the relationship between single nucleotide
      polymorphism (SNP) rs2295080 in mTOR promoter region and the risk of gastric
      cancer (GC). METHODS: Seven hundred and fifty-three (753) gastric adenocarcinoma
      patients and 854 matched healthy subjects were recruited in the cancer
      association study and 60 tissues were used to test the expression of mTOR.
      Unconditional logistic regression was selected to evaluate the association
      between the rs2295080 T>G polymorphism and GC risk. We then examined the
      functionality of this promoter genetic variant by luciferase assay and EMSA.
      RESULTS: Individuals with G allele had a 23% decreased risk of GC, comparing with
      those carrying T allele (adjusted OR = 0.77, 95% CI = 0.65-0.92). This protective
      effect of G allele stood out better in male group. Meanwhile, GC patients
      carrying TG/GG genotype also displayed a decreased mRNA level of mTOR (P =
      0.004). In luciferase assay, T allele tended to enhance the transcriptional
      activity of mTOR with an approximate 0.5-fold over G allele. Furthermore, EMSA
      tests explained that different alleles of rs2295080 displayed different
      affinities to some transcriptional factor. CONCLUSION: The mTOR promoter
      polymorphism rs2295080 was significantly associated with GC risk. This SNP, which
      effectively influenced the expression of mTOR, may be a new biomarker of early
      diagnosis of gastric cancer and a suitable indicator of utilizing mTOR inhibitor
      for treatment of GC.

PMID- 23555893
TI  - TALEN-based gene disruption in the dengue vector Aedes aegypti.
AB  - In addition to its role as the primary vector for dengue viruses, Aedes aegypti
      has a long history as a genetic model organism for other bloodfeeding mosquitoes,
      due to its ease of colonization, maintenance and reproductive productivity.
      Though its genome has been sequenced, functional characterization of many Ae.
      aegypti genes, pathways and behaviors has been slow. TALE nucleases (TALENs) have
      been used with great success in a number of organisms to generate site-specific
      DNA lesions. We evaluated the ability of a TALEN pair to target the Ae. aegypti
      kmo gene, whose protein product is essential in the production of eye
      pigmentation. Following injection into pre-blastoderm embryos, 20-40% of fertile
      survivors produced kmo alleles that failed to complement an existing kh(w)
      mutation. Most of these individuals produced more than 20% white-eyed progeny,
      with some producing up to 75%. Mutant alleles were associated with lesions of 1-7
      bp specifically at the selected target site. White-eyed individuals could also be
      recovered following a blind intercross of G1 progeny, yielding several new white
      eyed strains in the genetic background of the sequenced Liverpool strain. We
      conclude that TALENs are highly active in the Ae. aegypti germline, and have the
      potential to transform how reverse genetic experiments are performed in this
      important disease vector.

PMID- 23555894
TI  - Estimating premorbid cognitive abilities in low-educated populations.
AB  - OBJECTIVE: To develop an informant-based instrument that would provide a valid
      estimate of premorbid cognitive abilities in low-educated populations. METHODS: A
      questionnaire was drafted by focusing on the premorbid period with a 10-year time
      frame. The initial pool of items was submitted to classical test theory and a
      factorial analysis. The resulting instrument, named the Premorbid Cognitive
      Abilities Scale (PCAS), is composed of questions addressing educational
      attainment, major lifetime occupation, reading abilities, reading habits, writing
      abilities, calculation abilities, use of widely available technology, and the
      ability to search for specific information. The validation sample was composed of
      132 older Brazilian adults from the following three demographically matched
      groups: normal cognitive aging (n = 72), mild cognitive impairment (n = 33), and
      mild dementia (n = 27). The scores of a reading test and a neuropsychological
      battery were adopted as construct criteria. Post-mortem inter-informant
      reliability was tested in a sub-study with two relatives from each deceased
      individual. RESULTS: All items presented good discriminative power, with
      corrected item-total correlation varying from 0.35 to 0.74. The summed score of
      the instrument presented high correlation coefficients with global cognitive
      function (r = 0.73) and reading skills (r = 0.82). Cronbach's alpha was 0.90,
      showing optimal internal consistency without redundancy. The scores did not
      decrease across the progressive levels of cognitive impairment, suggesting that
      the goal of evaluating the premorbid state was achieved. The intraclass
      correlation coefficient was 0.96, indicating excellent inter-informant
      reliability. CONCLUSION: The instrument developed in this study has shown good
      properties and can be used as a valid estimate of premorbid cognitive abilities
      in low-educated populations. The applicability of the PCAS, both as an estimate
      of premorbid intelligence and cognitive reserve, is discussed.

PMID- 23555895
TI  - Comparison of regional cerebral blood flow responses to hypoglycemia using pulsed
      arterial spin labeling and positron emission tomography.
AB  - Different brain regions sense and modulate the counterregulatory responses that
      can occur in response to declining plasma glucose levels. The aim of this study
      was to determine if changes in regional cerebral blood flow (rCBF) during
      hypoglycemia relative to euglycemia are similar for two imaging modalities-pulsed
      arterial spin labeling magnetic resonance imaging (PASL-MRI) and positron
      emission tomography (PET). Nine healthy non-diabetic participants underwent a
      hyperinsulinemic euglycemic (92+/-3 mg/dL) - hypoglycemic (53+/-1 mg/dL) clamp.
      Counterregulatory hormone levels were collected at each of these glycemic levels
      and rCBF measurements within the previously described network of hypoglycemia
      responsive regions (thalamus, medial prefrontal cortex and globus pallidum) were
      obtained using PASL-MRI and [(15)O] water PET. In response to hypoglycemia, rCBF
      was significantly increased in the thalamus, medial prefrontal cortex, and globus
      pallidum compared to euglycemia for both PASL-MRI and PET methodologies. Both
      imaging techniques found similar increases in rCBF in the thalamus, medial
      prefrontal cortex, and globus pallidum in response to hypoglycemia. These brain
      regions may be involved in the physiologic and symptom responses to hypoglycemia.
      Compared to PET, PASL-MRI may provide a less invasive, less expensive method for
      assessing changes in rCBF during hypoglycemia without radiation exposure.

PMID- 23555896
TI  - Progressive adaptation in physical activity and neuromuscular performance during
      520d confinement.
AB  - To understand whether prolonged confinement results in reductions in physical
      activity and adaptation in the musculoskeletal system, six subjects were measured
      during 520 d isolation in the Mars500 study. We tested the hypothesis that
      physical activity reduces in prolonged confinement and that this would be
      associated with decrements of neuromuscular performance. Physical activity, as
      measured by average acceleration of the body's center of mass ("activity
      temperature") using the actibelt(r) device, decreased progressively over the
      course of isolation (p<0.00001). Concurrently, countermovement jump power and
      single-leg hop force decreased during isolation (p<0.001) whilst grip force did
      not change (p>=0.14). Similar to other models of inactivity, greater decrements
      of neuromuscular performance occurred in the lower-limb than in the upper-limb.
      Subject motivational state increased non-significantly (p = 0.20) during
      isolation, suggesting reductions in lower-limb neuromuscular performance were
      unrelated to motivation. Overall, we conclude that prolonged confinement is a
      form of physical inactivity and is associated with adaptation in the
      neuromuscular system.

PMID- 23555898
TI  - Emerging variability in HIV-1 genetics among recently infected individuals in
      Yunnan, China.
AB  - BACKGROUND: Yunnan has the longest endured Human Immunodeficiency Virus-1 (HIV-1)
      epidemic in China, and the genetic diversity of HIV-1 constitutes an essential
      characteristic of molecular epidemiology in this region. To obtain a more
      comprehensive picture of the dynamic changes in Yunnan's HIV-1 epidemic, a cross
      sectional molecular epidemiological investigation was carried out among recently
      infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced partial gag
      (HXB2?781-1861) and env (HXB2?7002-7541) genes from 308 plasma samples of
      recently infected patients. With phylogenetic analysis, 130 specimens generated
      interpretable genotyping data. We found that the circulating genotypes included:
      CRF08_BC (40.8%), unique recombinant forms (URFs, 27.7%), CRF01_AE (18.5%),
      CRF07_BC (9.2%), subtype B (2.3%) and C (1.5%). CRF08_BC was the most common
      genotype, and was predominant in both intravenous drug users (IDUs) and
      heterosexually transmitted populations. CRF08_BC and CRF07_BC still predominated
      in eastern Yunnan, but CRF08_BC showed increasing prevalence in western Yunnan.
      Strikingly, the URFs raised dramatically in most regions of Yunnan. Seven
      different types of URFs were detected from 12 prefectures, suggesting that
      complicated and frequent recombination is a salient feature of Yunnan's HIV-1
      epidemic. Among URFs, two BC clusters with distinctive recombination patterns
      might be potential new CRF_BCs. CRF01_AE was no longer confined to the
      prefectures bordering Myanmar, and had spread to the eastern part of Yunnan,
      especially the capital city of Kunming, with a large number of infections in the
      transient population. The ratios of the main genotypes showed no statistical
      differences between infected IDUs and heterosexually transmitted infections.
      CONCLUSIONS/SIGNIFICANCE: The changing patterns of the dominant HIV-1 genotypes
      in Yunnan indicate the complex evolving dynamic nature of the epidemic.
      Understanding new trends in molecular epidemiology of HIV-1 infection is critical
      for adjusting current prevention strategies and vaccine development in Yunnan.

PMID- 23555897
TI  - The DAO gene is associated with schizophrenia and interacts with other genes in
      the Taiwan Han Chinese population.
AB  - BACKGROUND: Schizophrenia is a highly heritable disease with a polygenic mode of
      inheritance. Many studies have contributed to our understanding of the genetic
      underpinnings of schizophrenia, but little is known about how interactions among
      genes affect the risk of schizophrenia. This study aimed to assess the
      associations and interactions among genes that confer vulnerability to
      schizophrenia and to examine the moderating effect of neuropsychological
      impairment. METHODS: We analyzed 99 SNPs from 10 candidate genes in 1,512 subject
      samples. The permutation-based single-locus, multi-locus association tests, and a
      gene-based multifactorial dimension reduction procedure were used to examine
      genetic associations and interactions to schizophrenia. RESULTS: We found that no
      single SNP was significantly associated with schizophrenia. However, a risk
      haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene,
      was strongly associated with schizophrenia. Interaction analyses identified
      multiple between-gene and within-gene interactions. Between-gene interactions
      including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for
      CACNG2 were found among schizophrenia subjects with severe sustained attention
      deficits, suggesting a modifying effect of impaired neuropsychological
      functioning. Other interactions such as the within-gene interaction of DAO and
      the between-gene interaction of DAO and PTK2B were consistently identified
      regardless of stratification by neuropsychological dysfunction. Importantly,
      except for the within-gene interaction of CACNG2, all of the identified risk
      haplotypes and interactions involved SNPs from DAO. CONCLUSIONS: These results
      suggest that DAO, which is involved in the N-methyl-d-aspartate receptor
      regulation, signaling and glutamate metabolism, is the master gene of the genetic
      associations and interactions underlying schizophrenia. Besides, the interaction
      between DAO and RASD2 has provided an insight in integrating the glutamate and
      dopamine hypotheses of schizophrenia.

PMID- 23555899
TI  - Conserved function of core clock proteins in the gymnosperm Norway spruce (Picea
      abies L. Karst).
AB  - From studies of the circadian clock in the plant model species Arabidopsis
      (Arabidopsis thaliana), a number of important properties and components have
      emerged. These include the genes CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), GIGANTEA
      (GI), ZEITLUPE (ZTL) and TIMING OF CAB EXPRESSION 1 (TOC1 also known as PSEUDO
      RESPONSE REGULATOR 1 (PRR1)) that via gene expression feedback loops participate
      in the circadian clock. Here, we present results from ectopic expression of four
      Norway spruce (Picea abies) putative homologs (PaCCA1, PaGI, PaZTL and PaPRR1) in
      Arabidopsis, their flowering time, circadian period length, red light response
      phenotypes and their effect on endogenous clock genes were assessed. For PaCCA1
      ox and PaZTL-ox the results were consistent with Arabidopsis lines overexpressing
      the corresponding Arabidopsis genes. For PaGI consistent results were obtained
      when expressed in the gi2 mutant, while PaGI and PaPRR1 expressed in wild type
      did not display the expected phenotypes. These results suggest that protein
      function of PaCCA1, PaGI and PaZTL are at least partly conserved compared to
      Arabidopsis homologs, however further studies are needed to reveal the protein
      function of PaPRR1. Our data suggest that components of the three-loop network
      typical of the circadian clock in angiosperms were present before the split of
      gymnosperms and angiosperms.

PMID- 23555901
TI  - ARF6 regulates neuron differentiation through glucosylceramide synthase.
AB  - The small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in
      addition been shown to regulate neuron differentiation. Here we investigated
      whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the
      cellular lipid composition. We showed that knockdown of ARF6 by siRNA in Neuro-2a
      cells increased neuronal outgrowth as expected. ARF6 knockdown also resulted in
      increased glucosylceramide levels and decreased sphingomyelin levels, but did not
      affect the levels of ceramide or phospholipids. We speculated that the ARF6
      knockdown-induced increase in glucosylceramide was caused by an effect on
      glucosylceramide synthase and, in agreement, showed that ARF6 knockdown increased
      the mRNA levels and activity of glucosylceramide synthase. Finally, we showed
      that incubation of Neuro-2a cells with the glucosylceramide synthase inhibitor D
      threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) normalized the
      increased neuronal outgrowth induced by ARF6 knockdown. Our results thus show
      that ARF6 regulates neuronal differentiation through an effect on
      glucosylceramide synthase and glucosylceramide levels.

PMID- 23555900
TI  - Up-regulation of RACK1 by TGF-beta1 promotes hepatic fibrosis in mice.
AB  - Liver fibrosis represents the consequences of a sustained wound healing response
      to chronic liver injury, and activation of quiescent hepatic stellate cells
      (HSCs) into a myofibroblast-like phenotype is considered as the central event of
      liver fibrosis. RACK1, the receptor for activated C-kinase 1, is a classical
      scaffold protein implicated in numerous signaling pathways and cellular
      processes; however, the role of RACK1 in liver fibrosis is little defined.
      Herein, we report that RACK1 is up-regulated in activated HSCs in transforming
      growth factor beta 1 (TGF-beta1)-dependent manner both in vitro and in vivo, and
      TGF-beta1 stimulates the expression of RACK1 through NF-kappaB signaling.
      Moreover, RACK1 promotes TGF-beta1 and platelet-derived growth factor (PDGF)
      mediated activation of pro-fibrogenic pathways as well as the differentiation,
      proliferation and migration of HSCs. Depletion of RACK1 suppresses the
      progression of TAA-induced liver fibrosis in vivo. In addition, the expression of
      RACK1 in fibrogenic cells also positively correlates well with the stage of liver
      fibrosis in clinical cases. Our results suggest RACK1 as a downstream target gene
      of TGF-beta1 involved in the modulation of liver fibrosis progression in vitro
      and in vivo, and propose a strategy to target RACK1 for liver fibrosis treatment.

PMID- 23555902
TI  - Requirement for core 2 O-glycans for optimal resistance to helminth infection.
AB  - The migration of lymphocytes to the small intestine is controlled by expression
      of the integrin alpha4beta7 and the chemokine receptor CCR9. However, the
      molecules that specifically regulate migration to the large intestine remain
      unclear. Immunity to infection with the large intestinal helminth parasite
      Trichuris muris is dependent upon CD4(+) T cells that migrate to the large
      intestine. We examine the role of specific chemokine receptors, adhesion
      molecules and glycosyltransferases in the development of protective immunity to
      Trichuris. Mice deficient in expression of the chemokine receptors CCR2 or CCR6
      were resistant to infection with Trichuris. Similarly, loss of CD34, CD43, CD44
      or PSGL-1 had no effect on resistance to infection. In contrast, simultaneous
      deletion of the Core2 beta1,6-N-acetylglucosaminyltransferase (C2GnT) enzymes
      C2GnT1 and C2Gnt2 resulted in delayed expulsion of worms. These results suggest
      that C2GnT-dependent modifications may play a role in migration of protective
      immune cells to the large intestine.

PMID- 23555903
TI  - Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell
      wall peptidoglycan in Mycobacterium tuberculosis.
AB  - ATP-dependent Mur ligases (Mur synthetases) play essential roles in the
      biosynthesis of cell wall peptidoglycan (PG) as they catalyze the ligation of key
      amino acid residues to the stem peptide at the expense of ATP hydrolysis, thus
      representing potential targets for antibacterial drug discovery. In this study we
      characterized the division/cell wall (dcw) operon and identified a promoter
      driving the co-transcription of mur synthetases along with key cell division
      genes such as ftsQ and ftsW. Furthermore, we have extended our previous
      investigations of MurE to MurC, MurD and MurF synthetases from Mycobacterium
      tuberculosis. Functional analyses of the pure recombinant enzymes revealed that
      the presence of divalent cations is an absolute requirement for their activities.
      We also observed that higher concentrations of ATP and UDP-sugar substrates were
      inhibitory for the activities of all Mur synthetases suggesting stringent control
      of the cytoplasmic steps of the peptidoglycan biosynthetic pathway. In line with
      the previous findings on the regulation of mycobacterial MurD and corynebacterial
      MurC synthetases via phosphorylation, we found that all of the Mur synthetases
      interacted with the Ser/Thr protein kinases, PknA and PknB. In addition, we
      critically analyzed the interaction network of all of the Mur synthetases with
      proteins involved in cell division and cell wall PG biosynthesis to re-evaluate
      the importance of these key enzymes as novel therapeutic targets in anti
      tubercular drug discovery.

PMID- 23555904
TI  - Impact of commonly used transplant immunosuppressive drugs on human NK cell
      function is dependent upon stimulation condition.
AB  - Lung transplantation is a recognised treatment for patients with end stage
      pulmonary disease. Transplant recipients receive life-long administration of
      immunosuppressive drugs that target T cell mediated graft rejection. However
      little is known of the impact on NK cells, which have the potential to be
      alloreactive in response to HLA-mismatched ligands on the lung allograft and in
      doing so, may impact negatively on allograft survival. NK cells from 20 healthy
      controls were assessed in response to Cyclosporine A, Mycophenolic acid (MPA;
      active form of Mycophenolate mofetil) and Prednisolone at a range of
      concentrations. The impact of these clinically used immunosuppressive drugs on
      cytotoxicity (measured by CD107a expression), IFN-gamma production and CFSE
      proliferation was assessed in response to various stimuli including MHC class-I
      negative cell lines, IL-2/IL-12 cytokines and PMA/Ionomycin. Treatment with MPA
      and Prednisolone revealed significantly reduced CD107a expression in response to
      cell line stimulation. In comparison, addition of MPA and Cyclosporine A
      displayed reduced CD107a expression and IFN-gamma production following
      PMA/Ionomycin stimulation. Diminished proliferation was observed in response to
      treatment with each drug. Additional functional inhibitors (LY294002, PD98059,
      Rottlerin, Rapamycin) were used to elucidate intracellular pathways of NK cell
      activation in response to stimulation with K562 or PMA-I. CD107a expression was
      significantly decreased with the addition of PD98059 following K562 stimulation.
      Similarly, CD107a expression significantly decreased following PMA-I stimulation
      with the addition of LY294002, PD98059 and Rottlerin. Ten lung transplant
      patients, not receiving immunosuppressive drugs pre-transplant, were assessed for
      longitudinal changes post-transplant in relation to the administration of
      immunosuppressive drugs. Individual patient dynamics revealed different
      longitudinal patterns of NK cell function post-transplantation. These results
      provide mechanistic insights into pathways of NK cell activation and show
      commonly administered transplant immunosuppression agents and clinical
      rejection/infection events have differential effects on NK cell function that may
      impact the immune response following lung transplantation.

PMID- 23555905
TI  - Expression of the glioma-associated oncogene homolog 1 (gli1) in advanced serous
      ovarian cancer is associated with unfavorable overall survival.
AB  - Recent evidence links aberrant activation of Hedgehog (Hh) signaling with the
      pathogenesis of several cancers including medulloblastoma, glioblastoma, melanoma
      as well as pancreas, colorectal, and prostate carcinomas. Here we investigated
      the role of the transcription factor Gli1 in ovarian cancer. To this end, the
      expression profile of Gli1 was examined in normal ovaries, ovarian tumors, and
      ovarian cancer cell lines, and the in vitro effects of a specific Hh-pathway
      blocker, KAAD-cyclopamine, or a specific Gli1 inhibitor (GANT58) on cell
      proliferation and on Hh target gene expression were also assessed. Results
      obtained showed that epithelial cells in ovarian cancer tissue express
      significantly higher levels of nuclear Gli1 than in normal ovarian tissue, where
      the protein was almost undetectable. In addition, multivariate analysis showed
      that nuclear Gli1 was independently associated to poor survival in advanced
      serous ovarian cancer patients (HR = 2.2, 95%CI 1.0-5.1, p = 0.04). In vitro
      experiments demonstrated Gli1 expression in the three ovarian carcinoma cell
      lines tested, A2780, SKOV-3 and OVCAR-3. Remarkably, although KAAD-cyclopamine
      led to decreased cell proliferation, this treatment did not inhibit hedgehog
      target gene expression in any of the three ovarian cancer cell lines, suggesting
      that the inhibition of cell proliferation was a nonspecific or toxic effect. In
      line with these data, no differences on cell proliferation were observed when
      cell lines were treated with GANT58. Overall, our clinical data support the role
      of Gli1 as a prognostic marker in advanced serous ovarian cancer and as a
      possible therapeutic target in this disease. However, our in vitro findings draw
      attention to the need for selection of appropriate experimental models that
      accurately represent human tumor for testing future therapies involving Hh
      pathway inhibitors.

PMID- 23555906
TI  - Iron: the forgotten driver of nitrous oxide production in agricultural soil.
AB  - In response to rising interest over the years, many experiments and several
      models have been devised to understand emission of nitrous oxide (N2O) from
      agricultural soils. Notably absent from almost all of this discussion is iron,
      even though its role in both chemical and biochemical reactions that generate N2O
      was recognized well before research on N2O emission began to accelerate. We
      revisited iron by exploring its importance alongside other soil properties
      commonly believed to control N2O production in agricultural systems. A set of
      soils from California's main agricultural regions was used to observe N2O
      emission under conditions representative of typical field scenarios. Results of
      multivariate analysis showed that in five of the twelve different conditions
      studied, iron ranked higher than any other intrinsic soil property in explaining
      observed emissions across soils. Upcoming studies stand to gain valuable
      information by considering iron among the drivers of N2O emission, expanding the
      current framework to include coupling between biotic and abiotic reactions.

PMID- 23555907
TI  - Surface area loss and increased sphericity account for the splenic entrapment of
      subpopulations of Plasmodium falciparum ring-infected erythrocytes.
AB  - Ex vivo perfusion of human spleens revealed innate retention of numerous cultured
      Plasmodium falciparum ring-infected red blood cells (ring-iRBCs). Ring-iRBC
      retention was confirmed by a microsphiltration device, a microbead-based
      technology that mimics the mechanical filtering function of the human spleen.
      However, the cellular alterations underpinning this retention remain unclear.
      Here, we use ImageStream technology to analyze infected RBCs' morphology and cell
      dimensions before and after fractionation with microsphiltration. Compared to
      fresh normal RBCs, the mean cell membrane surface area loss of trophozoite-iRBCs,
      ring-iRBCs and uninfected co-cultured RBCs (uRBCs) was 14.2% (range: 8.3-21.9%),
      9.6% (7.3-12.2%) and 3.7% (0-8.4), respectively. Microsphilters retained 100%,
      ~50% and 4% of trophozoite-iRBCs, ring-iRBCs and uRBCs, respectively. Retained
      ring-iRBCs display reduced surface area values (estimated mean, range: 17%, 15
      18%), similar to the previously shown threshold of surface-deficient RBCs
      retention in the human spleen (surface area loss: >18%). By contrast, ring-iRBCs
      that successfully traversed microsphilters had minimal surface area loss and
      normal sphericity, suggesting that these parameters are determinants of their
      retention. To confirm this hypothesis, fresh normal RBCs were exposed to
      lysophosphatidylcholine to induce a controlled loss of surface area. This
      resulted in a dose-dependent retention in microsphilters, with complete retention
      occurring for RBCs displaying >14% surface area loss. Taken together, these data
      demonstrate that surface area loss and resultant increased sphericity drive ring
      iRBC retention in microsphilters, and contribute to splenic entrapment of a
      subpopulation of ring-iRBCs. These findings trigger more interest in malaria
      research fields, including modeling of infection kinetics, estimation of parasite
      load, and analysis of risk factors for severe clinical forms. The determination
      of the threshold of splenic retention of ring-iRBCs has significant implications
      for diagnosis (spleen functionality) and drug treatment (screening of adjuvant
      therapy targeting ring-iRBCs).

PMID- 23555908
TI  - Laparoscopic hepatectomy for hepatic colorectal metastases -- a retrospective
      comparative cohort analysis and literature review.
AB  - BACKGROUND: Laparoscopic hepatectomy (LH) for management of hepatic colorectal
      metastases (HCRM) is commonly being performed; however, there are limited reports
      comparing LH outcomes with those of open hepatectomy (OH) procedure. The aim of
      the present study was to compare perioperative outcomes between the LH and OH
      procedures performed at a single medical center. METHODS: From Jan 2008 to May
      2012, 30 patients with pathologically confirmed HCRM underwent LH, and 140
      patients underwent OH at our hospital. Patients' demographics, perioperative
      outcomes were retrospectively analyzed. RESULTS: 2 patients (6.7%) in the LH
      group underwent laparotomies for intraoperative hemorrhage. The LH group had an
      increased surgical duration (235 min vs. 365 min, (P<0.001), shorter hospital
      stay (7.5 days vs. 11.5 days, P<0.001), and fewer complications (26.2% vs. 55%,
      P<0.001) than the OH group. However, in a matched cohort comparison of 30 LH
      cases and 30 OH cases, no significant variations were observed in the following
      parameters: surgical duration (235 min vs. 255 min, P = 0.23), positive margin
      rates (6.7% vs. 0.0%, P = 0.27), or postoperative hematological changes. LH
      patients had less estimated blood loss (215 ml vs. 385 ml, P<0.001), less
      morbidity (26.2% vs. 50%, P = 0.02), shorter hospital stay (7.5 days vs. 11.5
      days, P<0.001), and lower analgesic requests than with those in the OH group.
      CONCLUSIONS: LH for metastatic colorectal cancer is a safe and feasible
      treatment, even in patients who underwent prior laparotomy surgeries and provides
      significantly less morbidity and shorter hospital stay than OH, without
      compromising curability or increasing morbidity.

PMID- 23555909
TI  - Huntingtin's function in axonal transport is conserved in Drosophila
      melanogaster.
AB  - Huntington's disease (HD) is a devastating dominantly inherited neurodegenerative
      disorder caused by an abnormal polyglutamine expansion in the N-terminal part of
      the huntingtin (HTT) protein. HTT is a large scaffold protein that interacts with
      more than a hundred proteins and is probably involved in several cellular
      functions. The mutation is dominant, and is thought to confer new and toxic
      functions to the protein. However, there is emerging evidence that the mutation
      also alters HTT's normal functions. Therefore, HD models need to recapitulate
      this duality if they are to be relevant. Drosophila melanogaster is a useful in
      vivo model, widely used to study HD through the overexpression of full-length or
      N-terminal fragments of mutant human HTT. However, it is unclear whether
      Drosophila huntingtin (DmHTT) shares functions similar to the mammalian HTT.
      Here, we used various complementary approaches to analyze the function of DmHTT
      in fast axonal transport. We show that DmHTT interacts with the molecular motor
      dynein, associates with vesicles and co-sediments with microtubules. DmHTT co
      localizes with Brain-derived neurotrophic factor (BDNF)-containing vesicles in
      rat cortical neurons and partially replaces mammalian HTT in a fast axonal
      transport assay. DmHTT-KO flies show a reduced fast axonal transport of
      synaptotagmin vesicles in motoneurons in vivo. These results suggest that the
      function of HTT in axonal transport is conserved between flies and mammals. Our
      study therefore validates Drosophila melanogaster as a model to study HTT
      function, and its dysfunction associated with HD.

PMID- 23555911
TI  - Circadian rhythms differ between sexes and closely related species of Nasonia
      wasps.
AB  - Activity rhythms in 24 h light-dark cycles, constant darkness, and constant light
      conditions were analyzed in four different Nasonia species for each sex
      separately. Besides similarities, clear differences are evident among and within
      Nasonia species as well as between sexes. In all species, activity in a light
      dark cycle is concentrated in the photophase, typical for diurnal organisms.
      Contrary to most diurnal insect species so far studied, Nasonia follows Aschoff's
      rule by displaying long (>24 h) internal rhythms in constant darkness but short
      (<24 h) in constant light. In constant light, N. vitripennis males display robust
      circadian activity rhythms, whereas females are usually arrhythmic. In contrast
      to other Nasonia species, N. longicornis males display anticipatory activity,
      i.e. activity shortly before light-on in a light-dark cycle. As expected, N.
      oneida shows activity patterns similar to those of N. giraulti but with important
      differences in key circadian parameters. Differences in circadian activity
      patterns and parameters between species may reflect synchronization of specific
      life-history traits to environmental conditions. Scheduling mating or dispersion
      to a specific time of the day could be a strategy to avoid interspecific
      hybridization in Nasonia species that live in sympatry.

PMID- 23555910
TI  - A novel role of the Sp/KLF transcription factor KLF11 in arresting progression of
      endometriosis.
AB  - Endometriosis affects approximately 10% of young, reproductive-aged women.
      Disease associated pelvic pain; infertility and sexual dysfunction have a
      significant adverse clinical, social and financial impact. As precise disease
      etiology has remained elusive, current therapeutic strategies are empiric,
      unfocused and often unsatisfactory. Lack of a suitable genetic model has impaired
      further translational research in the field. In this study, we evaluated the role
      of the Sp/KLF transcription factor KLF11/Klf11 in the pathogenesis of
      endometriosis. KLF11, a human disease-associated gene is etiologically implicated
      in diabetes, uterine fibroids and cancer. We found that KLF11 expression was
      diminished in human endometriosis implants and further investigated its
      pathogenic role in Klf11-/- knockout mice with surgically induced endometriotic
      lesions. Lesions in Klf11-/- animals were large and associated with prolific
      fibrotic adhesions resembling advanced human disease in contrast to wildtype
      controls. To determine phenotype-specificity, endometriosis was also generated in
      Klf9-/- animals. Unlike in Klf11-/- mice, lesions in Klf9-/- animals were neither
      large, nor associated with a significant fibrotic response. KLF11 also bound to
      specific elements located in the promoter regions of key fibrosis-related genes
      from the Collagen, MMP and TGF-beta families in endometrial stromal cells. KLF11
      binding resulted in transcriptional repression of these genes. In summary, we
      identify a novel pathogenic role for KLF11 in preventing de novo disease
      associated fibrosis in endometriosis. Our model validates in vivo the phenotypic
      consequences of dysregulated Klf11 signaling. Additionally, it provides a robust
      means not only for further detailed mechanistic investigation but also the
      ability to test any emergent translational ramifications thereof, so as to expand
      the scope and capability for treatment of endometriosis.

PMID- 23555912
TI  - The Brazilian preference: cesarean delivery among immigrants in Portugal.
AB  - OBJECTIVE: To evaluate how the country of origin affects the probability of being
      delivered by cesarean section when giving birth at public Portuguese hospitals.
      STUDY DESIGN: Women delivered of a singleton birth (n = 8228), recruited from
      five public level III maternities (April 2005-August 2006) during the procedure
      of assembling a birth cohort, were classified according to the country of origin
      and her migration status as Portuguese (n = 7908), non-Portuguese European (n =
      84), African (n = 77) and Brazilian (n = 159). A Poisson model was used to
      evaluate the association between country of birth and cesarean section that was
      measured by adjusted prevalence ratio (PR) and respective 95% confidence
      intervals (95%CI). RESULTS: The cesarean section rate varied from 32.1% in non
      Portuguese European to 48.4% in Brazilian women (p = 0.008). After adjustment for
      potential confounders and compared to Portuguese women as a reference, Brazilian
      women presented significantly higher prevalence of cesarean section (PR = 1.26;
      95%CI: 1.08-1.47). The effect was more evident among multiparous women (PR =
      1.39; 95%CI: 1.12-1.73) and it was observed when cesarean section was performed
      either before labor (PR = 1.43; 95%CI: 0.99-2.06) or during labor (PR = 1.30;
      95%CI: 1.07-1.58). CONCLUSIONS: The rate of cesarean section was significantly
      higher among Brazilian women and it was independent of the presence of any known
      risk factors or usual clinical indications, suggesting that cultural background
      influences the mode of delivery overcoming the expected standard of care and
      outcomes in public health services.

PMID- 23555913
TI  - Reactivation of desensitized formyl peptide receptors by platelet activating
      factor: a novel receptor cross talk mechanism regulating neutrophil superoxide
      anion production.
AB  - Neutrophils express different chemoattractant receptors of importance for guiding
      the cells from the blood stream to sites of inflammation. These receptors
      communicate with one another, a cross talk manifested as hierarchical,
      heterologous receptor desensitization. We describe a new receptor cross talk
      mechanism, by which desensitized formyl peptide receptors (FPRdes) can be
      reactivated. FPR desensitization is induced through binding of specific FPR
      agonists and is reached after a short period of active signaling. The mechanism
      that transfers the receptor to a non-signaling desensitized state is not known,
      and a signaling pathway has so far not been described, that transfers FPRdes back
      to an active signaling state. The reactivation signal was generated by PAF
      stimulation of its receptor (PAFR) and the cross talk was uni-directional.
      LatrunculinA, an inhibitor of actin polymerization, induced a similar
      reactivation of FPRdes as PAF while the phosphatase inhibitor CalyculinA
      inhibited reactivation, suggesting a role for the actin cytoskeleton in receptor
      desensitization and reactivation. The activated PAFR could, however, reactivate
      FPRdes also when the cytoskeleton was disrupted prior to activation. The receptor
      cross talk model presented prophesies that the contact on the inner leaflet of
      the plasma membrane that blocks signaling between the G-protein and the FPR is
      not a point of no return; the receptor cross-talk from the PAFRs to the FPRdes
      initiates an actin-independent signaling pathway that turns desensitized
      receptors back to a signaling state. This represents a novel mechanism for
      amplification of neutrophil production of reactive oxygen species.

PMID- 23555915
TI  - Maternal complications and women's behavior in seeking care from skilled
      providers in North Gondar, Ethiopia.
AB  - BACKGROUND: Maternal complications are morbidities suffered during pregnancy
      through the postpartum period of 42 days. In Ethiopia, little is known about
      women's experience of complications and their care-seeking behavior. This study
      attempted to assess experiences related to obstetric complication and seeking
      assistance from a skilled provider among women who gave birth in the last 12
      months preceding the study. METHODS: This study was a cross-sectional survey of
      women who gave birth within one year preceding the study regardless of their
      delivery place. The study was carried out in six selected districts in North
      Gondar Zone, Amhara Region. Data was collected house-to-house in 12 selected
      clusters (kebeles) using a pretested Amharic questionnaire. During the survey,
      1,668 women were interviewed. Data entry was done using Epi Info version 3.5.3
      and was exported to SPSS for analysis. Logistic regression was applied to control
      confounders. RESULTS: Out of the total sample, 476 women (28.5%, 95% CI: 26.4%,
      30.7%) reported some kind of complication. The most common complications reported
      were; excessive bleeding and prolonged labor that occurred mostly at the time of
      delivery and postpartum period. Out of the total women who faced complications,
      248 (52.1%, 95% CI: 47.6%, 56.6%) sought assistance from a skilled provider.
      Inability to judge the severity of morbidities, distance/transport problems, lack
      of money/cost considerations and use of traditional options at home were the
      major reasons for not seeking care from skilled providers. Belonging to a
      wealthier quintile, getting antenatal care from a skilled provider and agreement
      of a woman in planning for possible complications were significantly associated
      with seeking assistance from a skilled provider. CONCLUSION: Nearly half of the
      women who faced complications did not use skilled providers at the time of
      obstetric complications. Cognitive, geographic, economic and cultural barriers
      were involved in not using skilled maternal care.

PMID- 23555914
TI  - HIV Tat induces expression of ICAM-1 in HUVECs: implications for miR-221/-222 in
      HIV-associated cardiomyopathy.
AB  - Cardiac involvement is a well-documented complication of human immunodeficiency
      virus-1 (HIV-1) infection. Previous studies have demonstrated increased adhesion
      of monocytes to human vascular endothelial cells in HIV-infected individuals. HIV
      Tat protein, which is the transactivator of transcription (Tat), plays a key role
      in activating endothelial cells. In the present study, we demonstrated that
      exposure of HUVECs to HIV Tat protein resulted in induced expression of cell
      adhesion molecules specifically ICAM-1, leading to increased adhesion of
      monocytes to the endothelium. This effect of Tat was mediated through activation
      of mitogen-activated protein kinases and downstream transcription factor NF
      kappaB. Increased expression of ICAM-1 was regulated by microRNA (miRNA) miR-221
      and to some extent by miR-222, both of which are known to target ICAM-1.
      Functional inhibition of the respective miRNAs with anti-miR oligonucleotides
      resulted in induction of ICAM-1 protein in HUVECs. Furthermore, Tat-stimulated
      regulation of ICAM-1 via miR-221/-222 involved the NF-kB-dependent pathway.
      Functional implication and specificity of up-regulated ICAM-1 was confirmed using
      the ICAM-1 neutralizing antibody in the in vitro cell adhesion assays. These
      findings were further confirmed in vivo using the HIV transgenic (Tg) rats. These
      animals not only demonstrated increased expression of ICAM-1 mRNA, with a
      concomitant reduction in the expression of miR-221 in the aorta and heart, but
      also had increased expression of the ICAM-1 protein that was predominantly in the
      endothelial cell layer. Taken together, these findings implicate that Tat
      mediated induction of ICAM-1 expression plays a critical role in monocyte
      adhesion observed in HIV-1-associated cardiomyopathies.

PMID- 23555916
TI  - Identification of SNPs in closely related Temperate Japonica rice cultivars using
      restriction enzyme-phased sequencing.
AB  - Very low polymorphism in the germplasm typically used by breeding programs poses
      a significant bottleneck with regards to molecular breeding and the exploitation
      of breeding materials for quantitative trait analyses. California rice cultivars,
      derived from a very small base of temperate japonica germplasm and having a
      relatively brief breeding history, are a good example. In this study, we employed
      a reduced representation sequencing approach called Restriction Enzyme Site
      Comparative Analysis (RESCAN) to simultaneously identify and genotype single
      nucleotide polymorphisms (SNPs) in forty-five rice cultivars representing the
      majority of the 100 year-old breeding history in California. Over 20,000 putative
      SNPs were detected relative to the Nipponbare reference genome which enabled the
      identification and analysis of inheritance of pedigree haplotypes. Haplotype
      blocks distinguishing modern California cultivars from each other and from the
      ancestral short grain temperate japonica cultivars were easily identified.
      Reduced representation sequencing methods such as RESCAN are a valuable
      alternative to SNP chip genotyping and low coverage whole genome sequencing.

PMID- 23555917
TI  - Relationship between malaria incidence and IgG levels to Plasmodium falciparum
      merozoite antigens in Malian children: impact of hemoglobins S and C.
AB  - Heterozygous hemoglobin (Hb) AS (sickle-cell trait) and HbAC are hypothesized to
      protect against Plasmodium falciparum malaria in part by enhancing naturally
      acquired immunity to this disease. To investigate this hypothesis, we compared
      antibody levels to four merozoite antigens from the P. falciparum 3D7 clone
      (apical membrane antigen 1, AMA1-3D7; merozoite surface protein 1, MSP1-3D7; 175
      kDa erythrocyte-binding antigen, EBA175-3D7; and merozoite surface protein 2,
      MSP2-3D7) in a cohort of 103 HbAA, 73 HbAS and 30 HbAC children aged 3 to 11
      years in a malaria-endemic area of Mali. In the 2009 transmission season we found
      that HbAS, but not HbAC, significantly reduced the risk of malaria compared to
      HbAA. IgG levels to MSP1 and MSP2 at the start of this transmission season
      inversely correlated with malaria incidence after adjusting for age and Hb type.
      However, HbAS children had significantly lower IgG levels to EBA175 and MSP2
      compared to HbAA children. On the other hand, HbAC children had similar IgG
      levels to all four antigens. The parasite growth-inhibitory activity of purified
      IgG samples did not differ significantly by Hb type. Changes in antigen-specific
      IgG levels during the 2009 transmission and 2010 dry seasons also did not differ
      by Hb type, and none of these IgG levels dropped significantly during the dry
      season. These data suggest that sickle-cell trait does not reduce the risk of
      malaria by enhancing the acquisition of IgG responses to merozoite antigens.

PMID- 23555918
TI  - Re-evaluation of PD-1 expression by T cells as a marker for immune exhaustion
      during SIV infection.
AB  - PD-1 expression is generally associated with exhaustion of T cells during chronic
      viral infections based on the finding that PD-1 expressing cells respond poorly
      to antigen activation and blockade of PD-1/PD-ligand interaction restores such
      antigen specific responses in vitro. We tested this hypothesis by examining PD-1
      expression on virus-specific CD8 T cells and total T cells in vivo to determine
      whether PD-1 expression constitutes a reliable marker of immune exhaustion during
      SIV infection. The expression of PD-1 and Ki67 was monitored longitudinally on T
      cell subsets in peripheral blood, bone marrow, lymph node and rectal biopsy
      specimens from rhesus macaques prior to and post infection with pathogenic
      SIVmac239. During the course of infection, a progressive negative correlation was
      noted between PD-1 density and Ki67 expression in p11CM(+) CD8(+) T cells, as
      seen in other studies. However, for total and memory CD4 and CD8 T cells, a
      positive correlation was observed between PD-1 and Ki67 expression. Thus, while
      the levels of non-proliferating PD-1(+) p11CM(+) CD8 T cells were markedly
      elevated with progressing infection, such an increase was not seen on total T
      cells. In addition, total memory PD1(+) T cells exhibited higher levels of CCR5
      than PD-1(-) T cells. Interestingly, few PD-1(+) CD8(+) T cells expressed CCR7
      compared to PD-1(+) CD4 T cells and PD-1(-) T cells. In conclusion, overall
      PD1(+) T cells likely represent a particular differentiation stage or trafficking
      ability rather than exhaustion and in the context of chronic SIV infection, the
      level of PD-1 expression by T cells does not by itself serve as a reliable marker
      for immune exhaustion.

PMID- 23555919
TI  - Pseudomonas aeruginosa cytotoxicity is attenuated at high cell density and
      associated with the accumulation of phenylacetic acid.
AB  - BACKGROUND: P. aeruginosa is known to cause acute cytotoxicity against various
      human and animal cells and tissues. METHODOLOGY/FINDINGS: Intriguingly, however,
      in this study we noticed that while a low cell density inoculum of P. aeruginosa
      caused severe cytotoxicity against human lung tissue cell line A549, increasing
      the cell density of bacterial inoculum led to decreased cytotoxicity. Addition of
      the supernatants from high density bacterial culture to low cell density inoculum
      protected the human cells from bacterial cytotoxic damage, suggesting that P.
      aeruginosa may produce and accumulate an inhibitory molecule(s) counteracting its
      pathogenic infection. The inhibitor was purified from the stationary-phase
      culture supernatants of P. aeruginosa strain PAO1 using bioassay-guided high
      performance liquid chromatography (HPLC), and characterized to be phenylacetic
      acid (PAA) by mass spectrometry and nuclear magnetic resonance spectroscopy.
      Microarray analysis revealed that treatment of P. aeruginosa with PAA down
      regulated the transcriptional expression of Type III secretion system (T3SS)
      genes and related regulatory genes including rsmA and vfr, which were confirmed
      by transcriptional and translational analysis. CONCLUSIONS: Identification of
      bacterial metabolite PAA as a T3SS-specific inhibitor explains this intriguing
      inverse cell-density-dependent-cytotoxicity phenomenon as T3SS is known to be a
      key virulence factor associated with cytotoxicity and acute infection. The
      findings may provide useful clues for design and development of new strategies to
      combat this formidable bacterial pathogen.

PMID- 23555921
TI  - Mortality risk amongst nursing home residents evacuated after the Fukushima
      nuclear accident: a retrospective cohort study.
AB  - BACKGROUND: Safety of evacuation is of paramount importance in disaster planning
      for elderly people; however, little effort has been made to investigate
      evacuation-related mortality risks. After the Fukushima Daiichi Nuclear Plant
      accident we conducted a retrospective cohort survival survey of elderly evacuees.
      METHODS: A total of 715 residents admitted to five nursing homes in Minamisoma
      city, Fukushima Prefecture in the five years before 11th March 2011 joined this
      retrospective cohort study. Demographic and clinical characteristics were drawn
      from facility medical records. Evacuation histories were tracked until the end of
      2011. The evacuation's impact on mortality was assessed using mortality incidence
      density and hazard ratios in Cox proportional hazards regression. RESULTS:
      Overall relative mortality risk before and after the earthquake was 2.68 (95% CI:
      2.04-3.49). There was a substantial variation in mortality risks across the
      facilities ranging from 0.77 (95% CI: 0.34-1.76) to 2.88 (95% CI: 1.74-4.76). No
      meaningful influence of evacuation distance on mortality was observed although
      the first evacuation from the original facility caused significantly higher
      mortality than subsequent evacuations, with a hazard ratio of 1.94 (95% CI: 1.07
      3.49). CONCLUSION: High mortality, due to initial evacuation, suggests that
      evacuation of the elderly was not the best life-saving strategy for the Fukushima
      nuclear disaster. Careful consideration of the relative risks of radiation
      exposure and the risks and benefits of evacuation is essential. Facility-specific
      disaster response strategies, including in-site relief and care, may have a
      strong influence on survival. Where evacuation is necessary, careful planning and
      coordination with other nursing homes, evacuation sites and government disaster
      agencies is essential to reduce the risk of mortality.

PMID- 23555920
TI  - Interhemispheric functional connectivity and its relationships with clinical
      characteristics in major depressive disorder: a resting state fMRI study.
AB  - BACKGROUND: Abnormalities in large-scale, structural and functional brain
      connectivity have been increasingly reported in patients with major depressive
      disorder (MDD). However, MDD-related alterations in functional interaction
      between the cerebral hemispheres are still not well understood. Resting state
      fMRI, which reveals spontaneous neural fluctuations in blood oxygen level
      dependent signals, provides a means to detect interhemispheric functional
      coherence. We examined the resting state functional connectivity (RSFC) between
      the two hemispheres and its relationships with clinical characteristics in MDD
      patients using a recently proposed measurement named "voxel-mirrored homotopic
      connectivity (VMHC)". METHODOLOGY/PRINCIPAL FINDINGS: We compared the
      interhemispheric RSFC, computed using the VMHC approach, of seventeen first
      episode drug-naive patients with MDD and seventeen healthy controls. Compared to
      the controls, MDD patients showed significant VMHC decreases in the medial
      orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions
      including the middle occipital gyrus and cuneus. In MDD patients, a negative
      correlation was found between VMHC of the fusiform gyrus and illness duration.
      Moreover, there were several regions whose VMHC showed significant negative
      correlations with the severity of cognitive disturbance, including the prefrontal
      regions, such as middle and inferior frontal gyri, and two regions in the
      cereballar crus. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the
      functional coordination between homotopic brain regions is impaired in MDD
      patients, thereby providing new evidence supporting the interhemispheric
      connectivity deficits of MDD. The significant correlations between the VMHC and
      clinical characteristics in MDD patients suggest potential clinical implication
      of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening
      method for evaluating MDD where neural connectivity is implicated in the
      pathophysiology.

PMID- 23555922
TI  - Egocentric representation acquired from offline map learning.
AB  - It is widely accepted that people establish allocentric spatial representation
      after learning a map. However, it is unknown whether people can directly acquire
      egocentric representation after map learning. In two experiments, the
      participants learned a distal environment through a map and then performed the
      egocentric pointing tasks in that environment under three conditions: with the
      heading aligned with the learning perspective (baseline), after 240 degrees 
      rotation from the baseline (updating), and after disorientation (disorientation).
      Disorientation disrupted the internal consistency of pointing among objects when
      the participants learned the sequentially displayed map, on which only one object
      name was displayed at a time while the location of "self" remained on the screen
      all the time. However, disorientation did not affect the internal consistency of
      pointing among objects when the participants learned the simultaneously displayed
      map. These results suggest that the egocentric representation can be acquired
      from a sequentially presented map.

PMID- 23555923
TI  - There is no association between microRNA gene polymorphisms and risk of triple
      negative breast cancer in a Chinese Han population.
AB  - Triple-negative breast cancer (TNBC) is defined by the lack of the expression of
      estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth
      factor receptor 2 (HER2). It is characterized by aggressive behavior, poor
      prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator
      of gene expression has played an important regulatory role in the malignancy.
      Dysregulation and/or mutation of the miRNAs may also contribute to the TNBC
      susceptibility since it is associated with the expression of ER, PR and HER2.
      Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for
      TNBC. We tried to validate the hypothesis that genetic variations in miRNA are
      associated with TNBC development, and identify candidate biomarkers for TNBC
      susceptibility and clinical treatment. We screened the genetic variants in all
      miRNA genes listed in the public database miRBase and NCBI. A total of 23 common
      SNPs in 22 miRNAs, which tagged the known common variants in the Chinese Han
      people with a minor allele frequency greater than 0.05, were genotyped. This case
      control study involved 191 patients with TNBC and 192 healthy female controls.
      Frequencies of SNPs were compared between cases and controls to identify the SNPs
      associated with TNBC susceptibility. No significant association was found between
      TNBC risk and the SNPs in the miRNA genes in the Chinese Han people (P>0.05), but
      this warrants further studies.

PMID- 23555924
TI  - TGF-beta1 regulation of estrogen production in mature rat Leydig cells.
AB  - BACKGROUND: Besides androgens, estrogens produced in Leydig cells are also
      crucial for mammalian germ cell differentiation. Transforming growth factor-beta1
      (TGF-beta1) is now known to have multiple effects on regulation of Leydig cell
      function. The objective of the present study is to determine whether TGF-beta1
      regulates estradiol (E2) synthesis in adult rat Leydig cells and then to assess
      the impact of TGF-beta1 on Cx43-based gap junctional intercellular communication
      (GJIC) between Leydig cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured
      Leydig cells were incubated in the presence of recombinant TGF-beta1 and the
      production of E2 as well as testosterone (T) were measured by RIA. The activity
      of P450arom was addressed by the tritiated water release assay and the expression
      of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The
      expression of Cx43 and GJIC were investigated with immunofluorescence and
      fluorescence recovery after photo-bleaching (FRAP), respectively. Results from
      this study show that TGF-beta1 down-regulates the level of E2 secretion and the
      activity of P450arom in a dose-dependent manner in adult Leydig cells. In
      addition, the expression of Cx43 and GJIC was closely related to the regulation
      of E2 and TGF-beta1, and E2 treatment in turn restored the inhibition of TGF
      beta1 on GJIC. CONCLUSIONS: Our results indicate, for the first time in adult rat
      Leydig cells, that TGF-beta1 suppresses P450arom activity, as well as the
      expression of the Cyp19 gene, and that depression of E2 secretion leads to down
      regulation of Cx43-based GJIC between Leydig cells.

PMID- 23555926
TI  - Risk factors of treatment-limiting anemia after substitution of zidovudine for
      stavudine in HIV-infected adult patients on antiretroviral treatment.
AB  - BACKGROUND: Anemia is the main concern among patients using a zidovudine (AZT)
      based antiretroviral treatment (ART). Some studies suggested weight-adjusted AZT
      dosing as a way to reduce toxicity. We analyzed the risk factors associated with
      AZT-induced anemia in a cohort using AZT as substitution for stavudine (D4T).
      METHODS: We retrospectively studied HIV-infected patients in a referral hospital
      in Phnom Penh, Cambodia between 2003 and 2011. Factors associated with AZT
      related anemia requiring AZT-discontinuation within the first year after AZT
      initiation were analyzed using Cox regression. RESULTS: Overall, 1180 patients,
      60.5% female, were included. At AZT initiation, the median hemoglobin was 12.7
      g/dL (IQR 11.7-13.9), the median weight: 51 kg (IQR 45-58) and the median time on
      ART prior to AZT substitution: 1.4 years (IQR 1.0-2.0). Within one year follow
      up, 139 patients (11.8%) developed anemia requiring AZT discontinuation. Overall,
      there was no independent association of body weight with AZT discontinuation. AZT
      discontinuation was associated with lower hemoglobin level when starting AZT;
      older age and taking D4T-based ART less than one year prior to AZT. In
      exploratory analysis, a linear increase in risk of grade 2-4 anemia with lower
      body weight was seen if starting AZT substitution within less than one year of
      D4T-based ART. CONCLUSION: Our findings argue against the need of weight-based
      dosing of AZT to reduce anemia among patients using AZT as substitution for D4T.
      Whether this also applies to ART-naive individuals remains to be assessed. Future
      studies with AZT dose reduction should assess efficacy and overall tolerance of
      AZT.

PMID- 23555927
TI  - Spider trait assembly patterns and resilience under fire-induced vegetation
      change in South Brazilian grasslands.
AB  - Disturbances induce changes on habitat proprieties that may filter organism's
      functional traits thereby shaping the structure and interactions of many trophic
      levels. We tested if communities of predators with foraging traits dependent on
      habitat structure respond to environmental change through cascades affecting the
      functional traits of plants. We monitored the response of spider and plant
      communities to fire in South Brazilian Grasslands using pairs of burned and
      unburned plots. Spiders were determined to the family level and described in
      feeding behavioral and morphological traits measured on each individual. Life
      form and morphological traits were recorded for plant species. One month after
      fire the abundance of vegetation hunters and the mean size of the chelicera
      increased due to the presence of suitable feeding sites in the regrowing
      vegetation, but irregular web builders decreased due to the absence of
      microhabitats and dense foliage into which they build their webs. Six months
      after fire rosette-form plants with broader leaves increased, creating a
      favourable habitat for orb web builders which became more abundant, while
      graminoids and tall plants were reduced, resulting in a decrease of proper
      shelters and microclimate in soil surface to ground hunters which became less
      abundant. Hence, fire triggered changes in vegetation structure that lead both to
      trait-convergence and trait-divergence assembly patterns of spiders along
      gradients of plant biomass and functional diversity. Spider individuals occurring
      in more functionally diverse plant communities were more diverse in their traits
      probably because increased possibility of resource exploitation, following the
      habitat heterogeneity hypothesis. Finally, as an indication of resilience, after
      twelve months spider communities did not differ from those of unburned plots. Our
      findings show that functional traits provide a mechanistic understanding of the
      response of communities to environmental change, especially when more than one
      trophic level is considered.

PMID- 23555925
TI  - Probing the interaction of brain fatty acid binding protein (B-FABP) with model
      membranes.
AB  - Brain fatty acid-binding protein (B-FABP) interacts with biological membranes and
      delivers polyunsaturated fatty acids (FAs) via a collisional mechanism. The
      binding of FAs in the protein and the interaction with membranes involve a motif
      called "portal region", formed by two small alpha-helices, A1 and A2, connected
      by a loop. We used a combination of site-directed mutagenesis and electron spin
      resonance to probe the changes in the protein and in the membrane model induced
      by their interaction. Spin labeled B-FABP mutants and lipidic spin probes
      incorporated into a membrane model confirmed that B-FABP interacts with micelles
      through the portal region and led to structural changes in the protein as well in
      the micelles. These changes were greater in the presence of LPG when compared to
      the LPC models. ESR spectra of B-FABP labeled mutants showed the presence of two
      groups of residues that responded to the presence of micelles in opposite ways.
      In the presence of lysophospholipids, group I of residues, whose side chains
      point outwards from the contact region between the helices, had their mobility
      decreased in an environment of lower polarity when compared to the same residues
      in solution. The second group, composed by residues with side chains situated at
      the interface between the alpha-helices, experienced an increase in mobility in
      the presence of the model membranes. These modifications in the ESR spectra of B
      FABP mutants are compatible with a less ordered structure of the portal region
      inner residues (group II) that is likely to facilitate the delivery of FAs to
      target membranes. On the other hand, residues in group I and micelle components
      have their mobilities decreased probably as a result of the formation of a
      collisional complex. Our results bring new insights for the understanding of the
      gating and delivery mechanisms of FABPs.

PMID- 23555928
TI  - Pmch-deficiency in rats is associated with normal adipocyte differentiation and
      lower sympathetic adipose drive.
AB  - The orexigenic neuropeptide melanin-concentrating hormone (MCH), a product of
      Pmch, is an important mediator of energy homeostasis. Pmch-deficient rodents are
      lean and smaller, characterized by lower food intake, body-, and fat mass. Pmch
      is expressed in hypothalamic neurons that ultimately are components in the
      sympathetic nervous system (SNS) drive to white and interscapular brown adipose
      tissue (WAT, iBAT, respectively). MCH binds to MCH receptor 1 (MCH1R), which is
      present on adipocytes. Currently it is unknown if Pmch-ablation changes adipocyte
      differentiation or sympathetic adipose drive. Using Pmch-deficient and wild-type
      rats on a standard low-fat diet, we analyzed dorsal subcutaneous and perirenal
      WAT mass and adipocyte morphology (size and number) throughout development, and
      indices of sympathetic activation in WAT and iBAT during adulthood. Moreover,
      using an in vitro approach we investigated the ability of MCH to modulate 3T3-L1
      adipocyte differentiation. Pmch-deficiency decreased dorsal subcutaneous and
      perirenal WAT mass by reducing adipocyte size, but not number. In line with this,
      in vitro 3T3-L1 adipocyte differentiation was unaffected by MCH. Finally, adult
      Pmch-deficient rats had lower norepinephrine turnover (an index of sympathetic
      adipose drive) in WAT and iBAT than wild-type rats. Collectively, our data
      indicate that MCH/MCH1R-pathway does not modify adipocyte differentiation,
      whereas Pmch-deficiency in laboratory rats lowers adiposity throughout
      development and sympathetic adipose drive during adulthood.

PMID- 23555929
TI  - Site specific mutation of the Zic2 locus by microinjection of TALEN mRNA in mouse
      CD1, C3H and C57BL/6J oocytes.
AB  - Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease
      domain fused to a DNA binding domain which is engineered to bind to any genomic
      sequence. These chimeric enzymes can be used to introduce a double strand break
      at a specific genomic site which then can become the substrate for error-prone
      non-homologous end joining (NHEJ), generating mutations at the site of cleavage.
      In this report we investigate the feasibility of achieving targeted mutagenesis
      by microinjection of TALEN mRNA within the mouse oocyte. We achieved high rates
      of mutagenesis of the mouse Zic2 gene in all backgrounds examined including
      outbred CD1 and inbred C3H and C57BL/6J. Founder mutant Zic2 mice (eight
      independent alleles, with frameshift and deletion mutations) were created in C3H
      and C57BL/6J backgrounds. These mice transmitted the mutant alleles to the
      progeny with 100% efficiency, allowing the creation of inbred lines. Mutant mice
      display a curly tail phenotype consistent with Zic2 loss-of-function. The
      efficiency of site-specific germline mutation in the mouse confirm TALEN mediated
      mutagenesis in the oocyte to be a viable alternative to conventional gene
      targeting in embryonic stem cells where simple loss-of-function alleles are
      required. This technology enables allelic series of mutations to be generated
      quickly and efficiently in diverse genetic backgrounds and will be a valuable
      approach to rapidly create mutations in mice already bearing one or more mutant
      alleles at other genetic loci without the need for lengthy backcrossing.

PMID- 23555930
TI  - Identification of a role for the ventral hippocampus in neuropeptide S-elicited
      anxiolysis.
AB  - Neuropeptide S (NPS) increasingly emerges as a potential novel treatment option
      for anxiety diseases like panic and posttraumatic stress disorder. However, the
      neural underpinnings of its anxiolytic action are still not clearly understood.
      Recently, we reported that neurons of the ventral hippocampus (VH) take up
      intranasally administered fluorophore-conjugated NPS and, moreover, that
      application of NPS to mouse brain slices affects neurotransmission and plasticity
      at hippocampal CA3-CA1 synapses. Although these previous findings define the VH
      as a novel NPS target structure, they leave open whether this brain region is
      directly involved in NPS-mediated anxiolysis and how NPS impacts on neuronal
      activity propagation in the VH. Here, we fill this knowledge gap by
      demonstrating, first, that microinjections of NPS into the ventral CA1 region are
      sufficient to reduce anxiety-like behavior of C57BL/6N mice and, second, that
      NPS, via the NPS receptor, rapidly weakens evoked neuronal activity flow from the
      dentate gyrus to area CA1 in vitro. Additionally, we show that intranasally
      applied NPS alters neurotransmission and plasticity at CA3-CA1 synapses in the
      same way as NPS administered to hippocampal slices. Thus, our study provides, for
      the first time, strong experimental evidence for a direct involvement of the VH
      in NPS-induced anxiolysis and furthermore presents a novel mechanism of NPS
      action.

PMID- 23555931
TI  - Selection of RNAs for constructing "Lighting-UP" biomolecular switches in
      response to specific small molecules.
AB  - RNA and protein are potential molecules that can be used to construct functional
      nanobiomaterials. Recent findings on riboswitches emphasize on the dominative
      function of RNAs in regulating protein functions through allosteric interactions
      between RNA and protein. In this study, we demonstrate a simple strategy to
      obtain RNAs that have a switching ability with respect to protein function in
      response to specific target molecules. RNA aptamers specific for small ligands
      and a trans-activation-responsive (TAR)-RNA were connected by random RNA
      sequences. RNAs that were allosterically bound to a trans-activator of
      transcription (Tat)-peptide in response to ligands were selected by repeated
      negative and positive selection in the absence and presence of the ligands,
      respectively. The selected RNAs interacted with artificially engineered Renilla
      Luciferase, in which the Tat-peptide was inserted within the Luciferase, in the
      presence of the specific ligand and triggered the "Lighting-UP" switch of the
      engineered Luciferase.

PMID- 23555932
TI  - Insights into the physiology and ecology of the brackish-water-adapted
      Cyanobacterium Nodularia spumigena CCY9414 based on a genome-transcriptome
      analysis.
AB  - Nodularia spumigena is a filamentous diazotrophic cyanobacterium that dominates
      the annual late summer cyanobacterial blooms in the Baltic Sea. But N. spumigena
      also is common in brackish water bodies worldwide, suggesting special adaptation
      allowing it to thrive at moderate salinities. A draft genome analysis of N.
      spumigena sp. CCY9414 yielded a single scaffold of 5,462,271 nucleotides in
      length on which genes for 5,294 proteins were annotated. A subsequent strand
      specific transcriptome analysis identified more than 6,000 putative
      transcriptional start sites (TSS). Orphan TSSs located in intergenic regions led
      us to predict 764 non-coding RNAs, among them 70 copies of a possible
      retrotransposon and several potential RNA regulators, some of which are also
      present in other N2-fixing cyanobacteria. Approximately 4% of the total coding
      capacity is devoted to the production of secondary metabolites, among them the
      potent hepatotoxin nodularin, the linear spumigin and the cyclic nodulapeptin.
      The transcriptional complexity associated with genes involved in nitrogen
      fixation and heterocyst differentiation is considerably smaller compared to other
      Nostocales. In contrast, sophisticated systems exist for the uptake and
      assimilation of iron and phosphorus compounds, for the synthesis of compatible
      solutes, and for the formation of gas vesicles, required for the active control
      of buoyancy. Hence, the annotation and interpretation of this sequence provides a
      vast array of clues into the genomic underpinnings of the physiology of this
      cyanobacterium and indicates in particular a competitive edge of N. spumigena in
      nutrient-limited brackish water ecosystems.

PMID- 23555933
TI  - Non-selective calcium channel blocker bepridil decreases secondary pathology in
      mice after photothrombotic cortical lesion.
AB  - Experimental studies have identified a complex link between neurodegeneration,
      beta-amyloid (Abeta) and calcium homeostasis. Here we asked whether early phase
      beta-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion
      and remote secondary pathology in the thalamus, and whether a non-selective
      calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and
      non-transgenic (n = 30) male mice (4-5 months) were subjected to unilateral
      cortical photothrombosis and treated with the non-selective calcium channel
      blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting
      administration 2 days after the operation. Animals were then perfused for
      histological analysis of infarct size, Abeta and calcium accumulation in the
      thalamus. Cortical photothrombosis resulted in a small infarct, which was
      associated with atypical Abeta and calcium accumulation in the ipsilateral
      thalamus. Transgenic mice had significantly smaller infarct volumes than non
      transgenic littermates (P<0.05) and ischemia-induced rodent Abeta accumulation in
      the thalamus was lower in transgenic mice compared to non-transgenic mice
      (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present
      data suggest less pronounced primary and secondary pathology in hAPPSL transgenic
      mice after ischemic cortical injury. Bepridil particularly decreased calcium
      pathology in the thalamus following ischemia.

PMID- 23555934
TI  - CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.
AB  - BACKGROUND: The impact of polymorphic cytochrome P450 CYP2D6 enzyme on
      oxycodone's metabolism and clinical efficacy is currently being discussed.
      However, there are only spare data from postoperative settings. The hypothesis of
      this study is that genotype dependent CYP2D6 activity influences plasma
      concentrations of oxycodone and its metabolites and impacts analgesic
      consumption. METHODS: Patients received oxycodone 0.05 mg/kg before emerging from
      anesthesia and patient-controlled analgesia (PCA) for the subsequent 48
      postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the
      initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites
      oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid
      chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping
      was performed and 121 patients were allocated to the following genotype groups:
      PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous
      subjects, intermediate metabolizers with decreased CYP2D6 activity), EM
      (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers,
      increased CYP2D6 activity). Primary endpoint was the genotype dependent
      metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary
      endpoint was the genotype dependent analgesic consumption with calculation of
      equianalgesic doses compared to the standard non-CYP dependent opioid
      piritramide. RESULTS: Metabolism differed between CYP2D6 genotypes. Mean (95%-CI)
      oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18
      (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p =
      0.005). Oxycodone consumption up to the 12(th) hour was highest in PM (p =
      0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone
      for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not
      differ between genotypes. CONCLUSIONS: In this postoperative setting, the number
      of functionally active CYP2D6 alleles had an impact on oxycodone metabolism. The
      genotype also impacted analgesic consumption, thereby causing variation of
      equianalgesic doses piritramide : oxycodone. Different analgesic needs by
      genotypes were met by PCA technology in this postoperative cohort.

PMID- 23555935
TI  - HIV-1 p24(gag) derived conserved element DNA vaccine increases the breadth of
      immune response in mice.
AB  - Viral diversity is considered a major impediment to the development of an
      effective HIV-1 vaccine. Despite this diversity, certain protein segments are
      nearly invariant across the known HIV-1 Group M sequences. We developed
      immunogens based on the highly conserved elements from the p24(gag) region
      according to two principles: the immunogen must (i) include strictly conserved
      elements of the virus that cannot mutate readily, and (ii) exclude both HIV
      regions capable of mutating without limiting virus viability, and also
      immunodominant epitopes located in variable regions. We engineered two HIV-1
      p24(gag) DNA immunogens that express 7 highly Conserved Elements (CE) of 12-24
      amino acids in length and differ by only 1 amino acid in each CE ('toggle site'),
      together covering >99% of the HIV-1 Group M sequences. Altering intracellular
      trafficking of the immunogens changed protein localization, stability, and also
      the nature of elicited immune responses. Immunization of C57BL/6 mice with
      p55(gag) DNA induced poor, CD4(+) mediated cellular responses, to only 2 of the 7
      CE; in contrast, vaccination with p24CE DNA induced cross-clade reactive, robust
      T cell responses to 4 of the 7 CE. The responses were multifunctional and
      composed of both CD4(+) and CD8(+) T cells with mature cytotoxic phenotype. These
      findings provide a method to increase immune response to universally conserved
      Gag epitopes, using the p24CE immunogen. p24CE DNA vaccination induced humoral
      immune responses similar in magnitude to those induced by p55(gag), which
      recognize the virus encoded p24(gag) protein. The inclusion of DNA immunogens
      composed of conserved elements is a promising vaccine strategy to induce broader
      immunity by CD4(+) and CD8(+) T cells to additional regions of Gag compared to
      vaccination with p55(gag) DNA, achieving maximal cross-clade reactive cellular
      and humoral responses.

PMID- 23555937
TI  - Dual task performance in normal aging: a comparison of choice reaction time
      tasks.
AB  - This study examined dual task performance in 28 younger (18-30 years) and 28
      older (>60 years) adults using two sets of choice reaction time (RT) tasks paired
      with digit tasks. Set one paired simple choice RT with digit forward; set two
      paired complex choice RT with digit backward. Each task within each set had easy
      and hard conditions. For the simple choice RT, participants viewed single letters
      and pressed a specified keyboard key if the letter was X or Z or a different key
      for other letters (easy). For the hard condition, there were 4 target letters (X,
      Z, O, Y). Digit forward consisted of 4 (easy) or 5 (hard) digits. For the complex
      choice RT, participants viewed 4*4 matrices of Xs and Os, and indicated whether
      four Xs (easy) or four Xs or four Os (hard) appeared in a row. Digit backward
      consisted of 3 (easy) or 4 (hard) digits. Within each set, participants performed
      every possible combination of tasks. We found that in the simple choice RT tasks
      older adults were significantly slower than, but as accurate as younger adults.
      In the complex choice RT tasks, older adults were significantly less accurate,
      but as fast as younger adults. For both age groups and both dual task sets, RT
      decreased and error rates increased with greater task difficulty. Older adults
      had greater dual task costs for error rates in the simple choice RT, whereas in
      the complex choice RT, it was the younger group that had greater dual task costs.
      Findings suggest that younger and older adults may adopt differential behavioral
      strategies depending on complexity and difficulty of dual tasks.

PMID- 23555936
TI  - Radioprotective effect of lidocaine on neurotransmitter agonist-induced secretion
      in irradiated salivary glands.
AB  - BACKGROUND: Previously we verified the radioprotective effect of lidocaine on the
      function and ultrastructure of salivary glands in rabbits. However, the
      underlying mechanism of lidocaine's radioprotective effect is unknown. We
      hypothesized that lidocaine, as a membrane stabilization agent, has a protective
      effect on intracellular neuroreceptor-mediated signaling and hence can help
      preserve the secretory function of salivary glands during radiotherapy. METHODS
      AND MATERIALS: Rabbits were irradiated with or without pretreatment with
      lidocaine before receiving fractionated radiation to a total dose of 35 Gy.
      Sialoscintigraphy and saliva total protein assay were performed before radiation
      and 1 week after the last radiation fraction. Isolated salivary gland acini were
      stimulated with either carbachol or adrenaline. Ca(2+) influx in response to the
      stimulation with these agonists was measured using laser scanning confocal
      microscopy. RESULTS: The uptake of activity and the excretion fraction of the
      parotid glands were significantly reduced after radiation, but lidocaine had a
      protective effect. Saliva total protein concentration was not altered after
      radiation. For isolated acini, Ca(2+) influx in response to stimulation with
      carbachol, but not adrenaline, was impaired after irradiation; lidocaine
      pretreatment attenuated this effect. CONCLUSIONS: Lidocaine has a radioprotective
      effect on the capacity of muscarinic agonist-induced water secretion in
      irradiated salivary glands.

PMID- 23555938
TI  - Feasibility of tomotherapy-based image-guided radiotherapy for locally advanced
      oropharyngeal cancer.
AB  - PURPOSE: The study aims to assess the feasibility of tomotherapy-based image
      guided (IGRT) radiotherapy for locally advanced oropharyngeal cancer. A
      retrospective review of 33 patients undergoing concurrent chemoradiation for
      locally advanced oropharyngeal cancers was conducted. Radiotherapy planning,
      treatment toxicity and loco-regional control were assessed. RESULTS: At a median
      follow-up of 32 months (6-47 months), no patient developed loco-regional
      recurrence. Two patients (6%) developed distant metastases. Grade 3-4 acute
      toxicity was respectively 72% and 25% for mucositis and gastrointestinal
      toxicity. Two patients (6%) had long-term dependence on tube feedings. Dose
      volume histogram demonstrated excellent target volume coverage and low radiation
      dose to the organs at risk for complications. CONCLUSIONS AND CLINICAL RELEVANCE:
      IGRT provides excellent loco-regional control but acute toxicity remains
      significant and needs to be addressed in future prospective trials. The
      feasibility of Tomotherapy to decrease radiation dose to the normal tissues
      merits further investigations.

PMID- 23555939
TI  - The effect of dietary prebiotics and probiotics on body weight, large intestine
      indices, and fecal bile acid profile in wild type and IL10-/- mice.
AB  - Previous studies have suggested roles of probiotics and prebiotics on body weight
      management and intestinal function. Here, the effects of a dietary prebiotic,
      inulin (50 mg/g diet), and probiotic, Bfidobacterium animalis subsp. lactis
      (Bb12) (final dose verified at 10(5) colony forming unit (cfu)/g diet, comparable
      to human consumption), were determined separately and in combination in mice
      using cellulose-based AIN-93G diets under conditions allowed for the growth of
      commensal bacteria. Continuous consumption of Bb12 and/or inulin did not affect
      food intake or body, liver, and spleen weights of young and adult mice. Fecal
      bile acid profiles were determined by nanoESI-MS/MS tandem mass spectrometry. In
      the presence of inulin, more bacterial deconjugation of taurine from primary bile
      acids was observed along with an increased cecal weight. Consumption of inulin in
      the absence or presence of Bb12 also increased the villus cell height in the
      proximal colon along with a trend of higher bile acid sulfation by intestinal
      cells. Feeding Bb12 alone at the physiological dose did not affect bile acid
      deconjugation and had little effect on other intestinal indices. Although
      interleukin (IL)10-null mice are susceptible to enterocolitis, they maintained
      the same body weight as the wild type mice under our specific pathogen-free
      housing condition and showed no signs of inflammation. Nevertheless, they had
      smaller cecum suggesting a mildly compromised intestinal development even before
      the disease manifestation. Our results are consistent with the notion that
      dietary factors such as prebiotics play important roles in the growth of
      intestinal microbiota and may impact on the intestinal health. In addition, fecal
      bile acid profiling could potentially be a non-invasive tool in monitoring the
      intestinal environment.

PMID- 23555940
TI  - Critical transitions in early embryonic aortic arch patterning and hemodynamics.
AB  - Transformation from the bilaterally symmetric embryonic aortic arches to the
      mature great vessels is a complex morphogenetic process, requiring both
      vasculogenic and angiogenic mechanisms. Early aortic arch development occurs
      simultaneously with rapid changes in pulsatile blood flow, ventricular function,
      and downstream impedance in both invertebrate and vertebrate species. These
      dynamic biomechanical environmental landscapes provide critical epigenetic cues
      for vascular growth and remodeling. In our previous work, we examined hemodynamic
      loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages
      18 and 24. We provided the first quantitative correlation between wall shear
      stress (WSS) and aortic arch diameter in the developing embryo, and observed that
      these two stages contained different aortic arch patterns with no inter-embryo
      variation. In the present study, we investigate these biomechanical events in the
      intermediate stage 21 to determine insights into this critical transition. We
      performed fluorescent dye microinjections to identify aortic arch patterns and
      measured diameters using both injection recordings and high-resolution optical
      coherence tomography. Flow and WSS were quantified with 3D computational fluid
      dynamics (CFD). Dye injections revealed that the transition in aortic arch
      pattern is not a uniform process and multiple configurations were documented at
      stage 21. CFD analysis showed that WSS is substantially elevated compared to both
      the previous (stage 18) and subsequent (stage 24) developmental time-points.
      These results demonstrate that acute increases in WSS are followed by a period of
      vascular remodeling to restore normative hemodynamic loading. Fluctuations in
      blood flow are one possible mechanism that impacts the timing of events such as
      aortic arch regression and generation, leading to the variable configurations at
      stage 21. Aortic arch variations noted during normal rapid vascular remodeling at
      stage 21 identify a temporal window of increased vulnerability to aberrant aortic
      arch morphogenesis with the potential for profound effects on subsequent
      cardiovascular morphogenesis.

PMID- 23555941
TI  - Characterization of gastric and neuronal histaminergic populations using a
      transgenic mouse model.
AB  - Histamine is a potent biogenic amine that mediates numerous physiological
      processes throughout the body, including digestion, sleep, and immunity. It is
      synthesized by gastric enterochromaffin-like cells, a specific set of
      hypothalamic neurons, as well as a subset of white blood cells, including mast
      cells. Much remains to be learned about these varied histamine-producing cell
      populations. Here, we report the validation of a transgenic mouse line in which
      Cre recombinase expression has been targeted to cells expressing histidine
      decarboxylase (HDC), which catalyzes the rate-limiting step in the synthesis of
      histamine. This was achieved by crossing the HDC-Cre mouse line with Rosa26
      tdTomato reporter mice, thus resulting in the expression of the fluorescent
      Tomato (Tmt) signal in cells containing Cre recombinase activity. As expected,
      the Tmt signal co-localized with HDC-immunoreactivity within the gastric mucosa
      and gastric submucosa and also within the tuberomamillary nucleus of the brain.
      HDC expression within Tmt-positive gastric cells was further confirmed by
      quantitative PCR analysis of mRNA isolated from highly purified populations of
      Tmt-positive cells obtained by fluorescent activated cell sorting (FACS). HDC
      expression within these FACS-separated cells was found to coincide with other
      markers of both ECL cells and mast cells. Gastrin expression was co-localized
      with HDC expression in a subset of histaminergic gastric mucosal cells. We
      suggest that these transgenic mice will facilitate future studies aimed at
      investigating the function of histamine-producing cells.

PMID- 23555942
TI  - Domains I and IV of annexin A2 affect the formation and integrity of in vitro
      capillary-like networks.
AB  - Annexin A2 (AnxA2) is a widely expressed multifunctional protein found in
      different cellular compartments. In spite of lacking a hydrophobic signal
      peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a
      role in angiogenesis. Increased extracellular levels of AnxA2 in tumours
      correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised
      that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial
      cell-cell interactions and motility. To address this question, we studied the
      effect of heterotetrameric and monomeric forms of AnxA2, as well as its two
      soluble domains on the formation and maintenance of capillary-like structures by
      using an in vitro co-culture system consisting of endothelial and smooth muscle
      cells. In particular, addition of purified domains I and IV of AnxA2 potently
      inhibited the vascular endothelial growth factor (VEGF)-dependent formation of
      the capillary-like networks in a dose-dependent manner. In addition, these AnxA2
      domains disrupted endothelial cell-cell contacts in preformed capillary-like
      networks, resulting in the internalisation of vascular endothelial (VE)-cadherin
      and the formation of VE-cadherin-containing filopodia-like structures between the
      endothelial cells, suggesting increased cell motility. Addition of monoclonal
      AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly
      inhibited network formation in the co-culture system. These results suggest that
      extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal
      role in angiogenesis. The exogenously added AnxA2 domains most likely mediate
      their effects by competing with endogenous AnxA2 for extracellular factors
      necessary for the initiation and maintenance of angiogenesis, such as those
      involved in the formation/integrity of cell-cell contacts.

PMID- 23555943
TI  - Characterization of adult rat astrocyte cultures.
AB  - Astrocytes, a major class of glial cells, regulate neurotransmitter systems,
      synaptic processing, ion homeostasis, antioxidant defenses and energy metabolism.
      Astrocyte cultures derived from rodent brains have been extensively used to
      characterize astrocytes' biochemical, pharmacological and morphological
      properties. The aims of this study were to develop a protocol for routine
      preparation and to characterize a primary astrocyte culture from the brains of
      adult (90 days old) Wistar rats. For this we used enzymatic digestion (trypsin
      and papain) and mechanical dissociation. Medium exchange occurred from 24 h after
      obtaining a culture and after, twice a week up to reach the confluence (around
      the 4(th) to 5(th) week). Under basal conditions, adult astrocytes presented a
      polygonal to fusiform and flat morphology. Furthermore, approximately 95% the
      cells were positive for the main glial markers, including GFAP, glutamate
      transporters, glutamine synthetase and S100B. Moreover, the astrocytes were able
      to take up glucose and glutamate. Adult astrocytes were also able to respond to
      acute H2O2 exposure, which led to an increase in reactive oxygen species (ROS)
      levels and a decrease in glutamate uptake. The antioxidant compound resveratrol
      was able to protect adult astrocytes from oxidative damage. A response of adult
      astrocytes to an inflammatory stimulus with LPS was also observed. Changes in the
      actin cytoskeleton were induced in stimulated astrocytes, most likely by a
      mechanism dependent on MAPK and Rho A signaling pathways. Taken together, these
      findings indicate that the culture model described in this study exhibits the
      biochemical and physiological properties of astrocytes and may be useful for
      elucidating the mechanisms related to the adult brain, exploring changes between
      neonatal and adult astrocytes, as well as investigating compounds involved in
      cytotoxicity and cytoprotection.

PMID- 23555944
TI  - Distinctive subdomains in the resorbing surface of osteoclasts.
AB  - We employed a novel technique to inspect the substrate-apposed surface of
      activated osteoclasts, the cells that resorb bone, in the scanning electron
      microscope. The surface revealed unexpected complexity. At the periphery of the
      cells were circles and crescents of individual or confluent nodules. These
      corresponded to the podosomes and actin rings that form a 'sealing zone',
      encircling the resorptive hemivacuole into which protons and enzymes are
      secreted. Inside these rings and crescents the osteoclast surface was covered
      with strips and patches of membrane folds, which were flattened against the
      substrate surface and surrounded by fold-free membrane in which many orifices
      could be seen. Corresponding regions of folded and fold-free membrane were found
      by transmission electron microscopy in osteoclasts incubated on bone. We
      correlated these patterns with the distribution of several proteins crucial to
      resorption. The strips and patches of membrane folds corresponded in distribution
      to vacuolar H+-ATPase, and frequently co-localized with F-actin. Cathepsin K
      localized to F-actin-free foci towards the center of cells with circular actin
      rings, and at the retreating pole of cells with actin crescents. The
      chloride/proton antiporter ClC-7 formed a sharply-defined band immediately inside
      the actin ring, peripheral to vacuolar H+-ATPase. The sealing zone of osteoclasts
      is permeable to molecules with molecular mass up to 10,000. Therefore, ClC-7
      might be distributed at the periphery of the resorptive hemivacuole in order to
      prevent protons from escaping laterally from the hemivacuole into the sealing
      zone, where they would dissolve the bone mineral. Since the activation of
      resorption is attributable to recognition of the alphaVbeta3 ligands bound to
      bone mineral, such leakage would, by dissolving bone mineral, release the ligands
      and so terminate resorption. Therefore, ClC-7 might serve not only to provide the
      counter-ions that enable proton pumping, but also to facilitate resorption by
      acting as a 'functional sealing zone'.

PMID- 23555945
TI  - Functional corticospinal projections from human supplementary motor area revealed
      by corticomuscular coherence during precise grip force control.
AB  - The purpose of the present study was to investigate whether corticospinal
      projections from human supplementary motor area (SMA) are functional during
      precise force control with the precision grip (thumb-index opposition). Since
      beta band corticomuscular coherence (CMC) is well-accepted to reflect efferent
      corticospinal transmission, we analyzed the beta band CMC obtained with
      simultaneous recording of electroencephalographic (EEG) and electromyographic
      (EMG) signals. Subjects performed a bimanual precise visuomotor force tracking
      task by applying isometric low grip forces with their right hand precision grip
      on a custom device with strain gauges. Concurrently, they held the device with
      their left hand precision grip, producing similar grip forces but without any
      precision constraints, to relieve the right hand. Some subjects also participated
      in a unimanual control condition in which they performed the task with only the
      right hand precision grip while the device was held by a mechanical grip. We
      analyzed whole scalp topographies of beta band CMC between 64 EEG channels and 4
      EMG intrinsic hand muscles, 2 for each hand. To compare the different
      topographies, we performed non-parametric statistical tests based on spatio
      spectral clustering. For the right hand, we obtained significant beta band CMC
      over the contralateral M1 region as well as over the SMA region during static
      force contraction periods. For the left hand, however, beta band CMC was only
      found over the contralateral M1. By comparing unimanual and bimanual conditions
      for right hand muscles, no significant difference was found on beta band CMC over
      M1 and SMA. We conclude that the beta band CMC found over SMA for right hand
      muscles results from the precision constraints and not from the bimanual aspect
      of the task. The result of the present study strongly suggests that the
      corticospinal projections from human SMA become functional when high precision
      force control is required.

PMID- 23555946
TI  - Integration of sensory force feedback is disturbed in CRPS-related dystonia.
AB  - Complex regional pain syndrome (CRPS) is characterized by pain and disturbed
      blood flow, temperature regulation and motor control. Approximately 25% of cases
      develop fixed dystonia. The origin of this movement disorder is poorly
      understood, although recent insights suggest involvement of disturbed force
      feedback. Assessment of sensorimotor integration may provide insight into the
      pathophysiology of fixed dystonia. Sensory weighting is the process of
      integrating and weighting sensory feedback channels in the central nervous system
      to improve the state estimate. It was hypothesized that patients with CRPS
      related dystonia bias sensory weighting of force and position toward position due
      to the unreliability of force feedback. The current study provides experimental
      evidence for dysfunctional sensory integration in fixed dystonia, showing that
      CRPS-patients with fixed dystonia weight force and position feedback differently
      than controls do. The study shows reduced force feedback weights in CRPS-patients
      with fixed dystonia, making it the first to demonstrate disturbed integration of
      force feedback in fixed dystonia, an important step towards understanding the
      pathophysiology of fixed dystonia.

PMID- 23555947
TI  - An archaeal homolog of proteasome assembly factor functions as a proteasome
      activator.
AB  - Assembly of the eukaryotic 20S proteasome is an ordered process involving several
      proteins operating as proteasome assembly factors including PAC1-PAC2 but
      archaeal 20S proteasome subunits can spontaneously assemble into an active
      cylindrical architecture. Recent bioinformatic analysis identified archaeal PAC1
      PAC2 homologs PbaA and PbaB. However, it remains unclear whether such assembly
      factor-like proteins play an indispensable role in orchestration of proteasome
      subunits in archaea. We revealed that PbaB forms a homotetramer and exerts a dual
      function as an ATP-independent proteasome activator and a molecular chaperone
      through its tentacle-like C-terminal segments. Our findings provide insights into
      molecular evolution relationships between proteasome activators and assembly
      factors.

PMID- 23555948
TI  - The impact of estradiol and 1,25(OH)2D3 on metabolic syndrome in middle-aged
      Taiwanese males.
AB  - In addition to adipocytokines, estradiol (E2) and vitamin D have been reported to
      affect insulin sensitivity, glucose homeostasis and body weight. However, studies
      about the impact of E2 and vitamin D on metabolic syndrome (MetS) are still
      limited. The aim of this study is to clarify the roles of circulating E2 and
      vitamin D on the risk of MetS in middle-aged Taiwanese males. A total of 655 male
      volunteers, including 243 subjects with MetS (mean age: 56.7+/-5.8 years) and 412
      normal controls (mean age: 55.1+/-3.6 years), were evaluated. Subjects with MetS
      had significantly lower circulating E2, 1,25(OH)2D3, and adiponectin, and higher
      leptin than those without MetS (P<0.001 for all comparisons). E2 and 1,25(OH)2D3
      were significantly associated with 4 individual components of MetS; more than
      adiponectin and leptin that were only associated with 3 individual components. In
      multivariate regression analysis, E2 (beta = -0.216, P<0.001) and 1,25(OH)2D3
      (beta = 0.067, P = 0.045) were still significant predictors of MetS independent
      of adiponectin and leptin. Further large studies are needed to confirm our
      preliminary results and elucidate the possible mechanism.

PMID- 23555949
TI  - Zoledronic acid produces combinatory anti-tumor effects with cisplatin on
      mesothelioma by increasing p53 expression levels.
AB  - We examined anti-tumor effects of zoledronic acid (ZOL), one of the
      bisphosphonates agents clinically used for preventing loss of bone mass, on human
      mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed
      activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A
      combinatory use of ZOL and cisplatin (CDDP), one of the first-line anti-cancer
      agents for mesothelioma, synergistically or additively produced the cytotoxicity
      on mesothelioma cells. Moreover, the combination achieved greater anti-tumor
      effects on mesothelioma developed in the pleural cavity than administration of
      either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced
      p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53
      protein expression levels. Down-regulation of p53 levels with siRNA however did
      not influence the ZOL-mediated cytotoxicity but negated the combinatory effects
      by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of
      adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated
      that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced
      cytotoxicity, played a role in the combinatory effects with a p53 up-regulating
      agent, and suggests a possible clinical use of ZOL to mesothelioma with anti
      cancer agents.

PMID- 23555950
TI  - An efficient low cost method for gene transfer to T lymphocytes.
AB  - Gene transfer to T lymphocytes has historically relied on retro and lentivirus,
      but recently transposon-based gene transfer is rising as a simpler and straight
      forward approach to achieve stable transgene expression. Transfer of expression
      cassettes to T lymphocytes remains challenging, being based mainly on commercial
      kits. AIMS: We herein report a convenient and affordable method based on in house
      made buffers, generic cuvettes and utilization of the widely available Lonza
      nucleofector II device to promote efficient gene transfer to T lymphocytes.
      RESULTS: This approach renders high transgene expression levels in primary human
      T lymphocytes (mean 45%, 41-59%), the hard to transfect murine T cells (mean 38%,
      36-42% for C57/BL6 strain) and human Jurkat T cell line. Cell viability levels
      after electroporation allowed further manipulations such as in vitro expansion
      and Chimeric Antigen Receptor (CAR) mediated gain of function for target cell
      lysis. CONCLUSIONS: We describe here an efficient general protocol for
      electroporation based modification of T lymphocytes. By opening access to this
      protocol, we expect that efficient gene transfer to T lymphocytes, for transient
      or stable expression, may be achieved by an increased number of laboratories at
      lower and affordable costs.

PMID- 23555951
TI  - Family-based association analysis confirms the role of the chromosome 9q21.32
      locus in the susceptibility of diabetic nephropathy.
AB  - A genome-wide association scan of type 1 diabetic patients from the GoKinD
      collections previously identified four novel diabetic nephropathy susceptibility
      loci that have subsequently been shown to be associated with diabetic nephropathy
      in unrelated patients with type 2 diabetes. To expand these findings, we examined
      whether single nucleotide polymorphisms (SNPs) at these susceptibility loci were
      associated with diabetic nephropathy in patients from the Joslin Study of
      Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the
      four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were
      genotyped in 66 extended families of European ancestry. Pedigrees from this
      collection contained an average of 18.5 members, including 2 to 14 members with
      type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached
      statistical significance with advanced diabetic nephropathy (P = 0.037 [adjusted
      P = 0.222]). When we expanded our definition of diabetic nephropathy to include
      individuals with high microalbuminuria, the strength of this association improved
      significantly (P = 1.42*10(-3) [adjusted P = 0.009]). This same locus also
      trended toward statistical significance with variation in urinary albumin
      excretion in family members with type 2 diabetes (P = 0.032 [adjusted P = 0.192])
      and in analyses expanded to include all relatives (P = 0.019 [adjusted P =
      0.114]). These data increase support that SNPs identified in the GoKinD
      collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility
      loci.

PMID- 23555952
TI  - PAPP5 is involved in the tetrapyrrole mediated plastid signalling during
      chloroplast development.
AB  - The initiation of chloroplast development in the light is dependent on nuclear
      encoded components. The nuclear genes encoding key components in the
      photosynthetic machinery are regulated by signals originating in the plastids.
      These plastid signals play an essential role in the regulation of photosynthesis
      associated nuclear genes (PhANGs) when proplastids develop into chloroplasts. One
      of the plastid signals is linked to the tetrapyrrole biosynthesis and
      accumulation of the intermediates the Mg-ProtoIX and its methyl ester Mg-ProtoIX
      ME. Phytochrome-Associated Protein Phosphatase 5 (PAPP5) was isolated in a
      previous study as a putative Mg-ProtoIX interacting protein. In order to
      elucidate if there is a biological link between PAPP5 and the tetrapyrrole
      mediated signal we generated double mutants between the Arabidopsis papp5 and the
      crd mutants. The crd mutant over-accumulates Mg-ProtoIX and Mg-ProtoIX-ME and the
      tetrapyrrole accumulation triggers retrograde signalling. The crd mutant exhibits
      repression of PhANG expression, altered chloroplast morphology and a pale
      phenotype. However, in the papp5crd double mutant, the crd phenotype is restored
      and papp5crd accumulated wild type levels of chlorophyll, developed proper
      chloroplasts and showed normal induction of PhANG expression in response to
      light. Tetrapyrrole feeding experiments showed that PAPP5 is required to respond
      correctly to accumulation of tetrapyrroles in the cell and that PAPP5 is most
      likely a component in the plastid signalling pathway down stream of the
      tetrapyrrole Mg-ProtoIX/Mg-ProtoIX-ME. Inhibition of phosphatase activity
      phenocopied the papp5crd phenotype in the crd single mutant demonstrating that
      PAPP5 phosphatase activity is essential to mediate the retrograde signal and to
      suppress PhANG expression in the crd mutant. Thus, our results suggest that PAPP5
      receives an inbalance in the tetrapyrrole biosynthesis through the accumulation
      of Mg-ProtoIX and acts as a negative regulator of PhANG expression during
      chloroplast biogenesis and development.

PMID- 23555953
TI  - Melanopsin gene polymorphism I394T is associated with pupillary light responses
      in a dose-dependent manner.
AB  - BACKGROUND: Melanopsin-containing intrinsically photosensitive retinal ganglion
      cells (ipRGCs) play an important role in non-image forming responses to light,
      such as circadian photoentrainment, light-induced melatonin suppression, and
      pupillary light response. Although it is known that there are some single
      nucleotide polymorphisms (SNPs) in the melanopsin (OPN4) gene in humans, the
      associations of the SNPs with non-image forming responses to light remains
      unclear. In the present study, we examined the associations of melanopsin gene
      polymorphisms with pupillary light response. METHODS: Japanese university
      students (mean age: 21.0 +/- 1.7 years) with the genotypes of TT (n = 38), TC (n
      = 28) and CC (n = 7) at rs1079610 (I394T) located in the coding region
      participated in the present study. They were matched by age and sex ratio. Dark
      adapted pupil size (<1 lx) was first measured. Then steady-state pupil size was
      measured during exposure to five lighting conditions (10 lx, 100 lx, 1000 lx,
      3000 lx, 6000 lx in the vertical direction at eye level). RESULTS: Significant
      interaction between the genotype of I394T (TT versus TC+CC) and luminance levels
      was found in pupil size. Under high illuminance levels (1000 lx, 3000 lx and 6000
      lx), pupil sizes in subjects with the C allele were significantly smaller than
      those in subjects with the TT genotype. On the other hand, pupil size in subjects
      with the C allele under low illuminance (<1 lx) was significantly larger than
      that in subjects with the TT genotype. Percentages of pupil constriction under
      high illuminance levels were significantly greater in subjects with the C allele
      than in subjects with the TT genotype. CONCLUSIONS: Human melanopsin gene
      polymorphism I394T interacted with irradiance in association with pupil size.
      This is the first evidence suggesting a functional connection between melanopsin
      gene polymorphism and pupillary light response as an index of non-image forming
      response to light.

PMID- 23555955
TI  - Spatial variation in the population structure and reproductive biology of
      Rimicaris hybisae (Caridea: Alvinocarididae) at hydrothermal vents on the Mid
      Cayman Spreading Centre.
AB  - The dynamics and microdistribution of faunal assemblages at hydrothermal vents
      often reflect the fine-scale spatial and temporal heterogeneity of the vent
      environment. This study examined the reproductive development and population
      structure of the caridean shrimp Rimicaris hybisae at the Beebe and Von Damm Vent
      Fields (Mid-Cayman Spreading Centre, Caribbean) using spatially discrete samples
      collected in January 2012. Rimicaris hybisae is gonochoric and exhibits
      iteroparous reproduction. Oocyte size-frequency distributions (21-823 um feret
      diameters) varied significantly among samples. Embryo development was
      asynchronous among females, which may result in asynchronous larval release for
      the populations. Specimens of R. hybisae from the Von Damm Vent Field (2294 m)
      were significantly larger than specimens from the Beebe Vent Field. Brooding
      females at Von Damm exhibited greater size-specific fecundity, possibly as a
      consequence of a non-linear relationship between fecundity and body size that was
      consistent across both vent fields. Samples collected from several locations at
      the Beebe Vent Field (4944-4972 m) revealed spatial variability in the sex
      ratios, population structure, size, and development of oocytes and embryos of
      this mobile species. Samples from the Von Damm Vent Field and sample J2-613-24
      from Beebe Woods exhibited the highest frequencies of ovigerous females and
      significantly female-biased sex ratios. Environmental variables within shrimp
      aggregations may influence the distribution of ovigerous females, resulting in a
      spatially heterogeneous pattern of reproductive development in R. hybisae, as
      found in other vent taxa.

PMID- 23555954
TI  - miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small
      cell lung cancer cells.
AB  - Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved
      in the development and progression of various types of cancers. However, its role
      in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this
      study was to investigate the contribution of miR-146a to various aspects of the
      malignant phenotype of human NSCLCs. In functional experiments, miR-146a
      suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream
      signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR
      146a also inhibited the migratory capacity of these NSCLC cells. On the other
      hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting
      EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal
      antibody (cetuximab). These effects were independent of the EGFR mutation status
      (wild type, sensitizing mutation or resistance mutation), but were less potent
      compared to the effects of siRNA targeting of EGFR. Our results suggest that
      these effects of miR-146a are due to its targeting of EGFR and NF-kappaB
      signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE)
      lung cancer samples, that low expression of miR-146a was correlated with advanced
      clinical TNM stages and distant metastasis in NSCLC (P<0.05). The patients with
      high miR-146a expression in their tumors showed longer progression-free survival
      (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients,
      P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC.
      Thus inducing miR-146a might be a therapeutic strategy for NSCLC.

PMID- 23555956
TI  - Genome and bioinformatic analysis of a HAdV-B14p1 virus isolated from a baby with
      pneumonia in Beijing, China.
AB  - The genome of HAdV-B14p1 strain BJ430, isolated from a six-month-old baby
      diagnosed with bronchial pneumonia at the Beijing Children's Hospital in December
      2010, was sequenced, analyzed, and compared with reference adenovirus genome
      sequences archived in GenBank. This genome is 34,762 bp in length, remarkably
      presenting 99.9% identity with the genome from HAdV14p1 strain 303600, which was
      isolated in the USA (2006). Even more remarkable, it is 99.7% identical with the
      HAdV-B14p (prototype "de Wit" strain) genome, isolated from The Netherlands in
      1955. The patient and its parents presumably had no or limited contact with
      persons from the USA and Ireland, both of which reported outbreaks of the re
      emergent virus HAdV-14p1 recently. These genome data, its analysis, and this
      report provide a reference for any additional HAdV-B14 outbreak in China and
      provide the basis for the development of adenovirus vaccines and molecular
      pathogen surveillance protocols in high-risk areas.

PMID- 23555957
TI  - Using multivalent adenoviral vectors for HIV vaccination.
AB  - Adenoviral vectors have been used for a variety of vaccine applications including
      cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to
      express antigens through transgene expression of a given antigen. For effective
      vaccine development it is often necessary to express or present multiple antigens
      to the immune system to elicit an optimal vaccine as observed preclinically with
      mosaic/polyvalent HIV vaccines or malaria vaccines. Due to the wide flexibility
      of Ad vectors they are an ideal platform for expressing large amounts of antigen
      and/or polyvalent mosaic antigens. Ad vectors that display antigens on their
      capsid surface can elicit a robust humoral immune response, the "antigen capsid
      incorporation" strategy. The adenoviral hexon protein has been utilized to
      display peptides in the majority of vaccine strategies involving capsid
      incorporation. Based on our abilities to manipulate hexon HVR2 and HVR5, we
      sought to manipulate HVR1 in the context of HIV antigen display for the first
      time ever. More importantly, peptide incorporation within HVR1 was utilized in
      combination with other HVRs, thus creating multivalent vectors. To date this is
      the first report where dual antigens are displayed within one Ad hexon particle.
      These vectors utilize HVR1 as an incorporation site for a seven amino acid region
      of the HIV glycoprotein 41, in combination with six Histidine incorporation
      within HVR2 or HVR5. Our study illustrates that these multivalent antigen vectors
      are viable and can present HIV antigen as well as His6 within one Ad virion
      particle. Furthermore, mouse immunizations with these vectors demonstrate that
      these vectors can elicit a HIV and His6 epitope-specific humoral immune response.

PMID- 23555958
TI  - Breakdown of methods for phasing and imputation in the presence of double
      genotype sharing.
AB  - In genome-wide association studies, results have been improved through imputation
      of a denser marker set based on reference haplotypes and phasing of the genotype
      data. To better handle very large sets of reference haplotypes, pre-phasing with
      only study individuals has been suggested. We present a possible problem which is
      aggravated when pre-phasing strategies are used, and suggest a modification
      avoiding the resulting issues with application to the MaCH tool, although the
      underlying problem is not specific to that tool. We evaluate the effectiveness of
      our remedy to a subset of Hapmap data, comparing the original version of MaCH and
      our modified approach. Improvements are demonstrated on the original data (phase
      switch error rate decreasing by 10%), but the differences are more pronounced in
      cases where the data is augmented to represent the presence of closely related
      individuals, especially when siblings are present (30% reduction in switch error
      rate in the presence of children, 47% reduction in the presence of siblings). The
      main conclusion of this investigation is that existing statistical methods for
      phasing and imputation of unrelated individuals might give results of sub-par
      quality if a subset of study individuals nonetheless are related. As the
      populations collected for general genome-wide association studies grow in size,
      including relatives might become more common. If a general GWAS framework for
      unrelated individuals would be employed on datasets with some related
      individuals, such as including familial data or material from domesticated
      animals, caution should also be taken regarding the quality of haplotypes. Our
      modification to MaCH is available on request and straightforward to implement. We
      hope that this mode, if found to be of use, could be integrated as an option in
      future standard distributions of MaCH.

PMID- 23555959
TI  - Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow
      stroma in diabetes mellitus.
AB  - BACKGROUND: Circulating Endothelial Progenitor Cell (EPC) levels are reduced in
      diabetes mellitus. This may be a consequence of impaired mobilization of EPC from
      the bone marrow. We hypothesized that under diabetic conditions, mobilization of
      EPC from the bone marrow to the circulation is impaired -at least partly- due to
      dysfunction of the bone marrow stromal compartment. METHODS: Diabetes was induced
      in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were
      characterized and quantified by flow cytometry at baseline and after mobilization
      with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU
      challenge. Interaction within the bone marrow environment between CD34(+)
      hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co
      cultures. To study progenitor cell-endothelial cell interaction under
      normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1
      transfected human endothelial cells was employed. RESULTS: In diabetic mice, bone
      marrow EPC levels were unaffected. However, circulating EPC levels in blood were
      lower at baseline and mobilization was attenuated. Diabetic mice failed to
      recover and repopulate from 5-FU injection. In vitro, primary cultured bone
      marrow stroma from diabetic mice was impaired in its capacity to support human
      CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of
      endothelial cells in vitro. CONCLUSION: EPC mobilization is impaired under
      experimental diabetic conditions and our data suggest that diabetes induces
      alterations in the progenitor cell supportive capacity of the bone marrow stroma,
      which could be partially responsible for the attenuated EPC mobilization and
      reduced EPC levels observed in diabetic patients.

PMID- 23555960
TI  - A combination of cytokines rescues highly purified leukemic CLL B-cells from
      spontaneous apoptosis in vitro.
AB  - B-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, is
      characterized by predominantly non-dividing malignant mature CD5+ B lymphocytes
      with an apoptosis defect. Various microenvironmental stimuli confer a growth
      advantage on these leukemic cells and extend their survival in vivo.
      Nevertheless, when cultured in vitro, CLL B-cells rapidly die from apoptosis.
      Certain cytokines may extend the survival capacity of CLL B-cells in vitro and
      individual anti-apoptotic effects of several cytokines have been reported. The
      potential cumulative effect of such cytokines has not been studied. We therefore
      investigated the effects on CLL B-cells survival in vitro of humoral factors,
      polyclonal lymphocyte activators and a combination of cytokines known for their
      anti-apoptotic effects. Purified CLL B-cells were cultured in the presence or
      absence of various soluble molecules and the leukemic cell response was assessed
      in terms of viability. Apoptotic cell death was detected by flow cytometry using
      annexinV and 7-amino-actinomycin. The survival of CLL B-cells in vitro was highly
      variable. When tested separately, cytokines (IL-2, -6, -10, -12, -15, -21, BAFF
      and APRIL) improved CLL B cell survival moderately; in combination, they
      significantly enhanced survival of these cells, even up to 7 days of culture. We
      also report that humoral factors from autologous serum are important for survival
      of these malignant cells. Our findings support the concept that the CLL
      microenvironment is critical and suggest that soluble factors may contribute
      directly to the prolonged survival of CLL B-cells. Therefore, the combination of
      cytokines we describe as providing strong resistance to apoptosis in vitro might
      be used to improve the treatment of CLL.

PMID- 23555961
TI  - Mycotoxin-containing diet causes oxidative stress in the mouse.
AB  - Mycotoxins which mainly consist of Aflatoxin (AF), Zearalenone (ZEN) and
      Deoxynivalenol (DON) are commonly found in many food commodities. Although each
      component has been shown to cause liver toxicity and oxidative stress in several
      species, there is no evidence regarding the effect of naturally contained
      multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the
      present study, mycotoxins-contaminated maize (AF 597 ug/kg, ZEN 729 ug/kg, DON
      3.1 mg/kg maize) was incorporated into the diet at three different doses (0, 5
      and 20%) to feed the mice, and blood and tissue samples were collected to examine
      the oxidative stress related indexes. The results showed that the indexes of
      liver, kidney and spleen were all increased and the liver and kidney morphologies
      changed in the mycotoxin-treated mice. Also, the treatment resulted in the
      elevated glutathione peroxidase (GPx) activity and malondialdehyde (MDA) level in
      the serum and liver, indicating the presence of the oxidative stress. Moreover,
      the decrease of catalase (CAT) activity in the serum, liver and kidney as well as
      superoxide dismutase (SOD) activity in the liver and kidney tissue further
      confirmed the occurrence of oxidative stress. In conclusion, our data indicate
      that the naturally contained mycotoxins are toxic in vivo and able to induce the
      oxidant stress in the mouse.

PMID- 23555962
TI  - Presentation of smoking-associated cues does not elicit dopamine release after
      one-hour smoking abstinence: A [11C]-(+)-PHNO PET study.
AB  - The presentation of drug-associated cues has been shown to elicit craving and
      dopamine release in the striatum of drug-dependent individuals. Similarly,
      exposure to tobacco-associated cues induces craving and increases the propensity
      to relapse in tobacco- dependent smokers. However, whether exposure to tobacco
      associated cues elicits dopamine release in the striatum of smokers remains to be
      investigated. We hypothesized that presentation of smoking-related cues compared
      to neutral cues would induce craving and elevation of intrasynaptic dopamine
      levels in subregions of the striatum and that the magnitude of dopamine release
      would be correlated with subjective levels of craving in briefly abstinent
      tobacco smokers. Eighteen participants underwent two [(11)C]-(+)-PHNO positron
      emission tomography (PET) scans after one-hour abstinence period: one during
      presentation of smoking-associated images and one during presentation of neutral
      images. Smoking cues significantly increased craving compared to neutral cues on
      one, but not all, craving measures; however, this increase in craving was not
      associated with overall significant differences in [(11)C]-(+)-PHNO binding
      potential (BPND) (an indirect measure of dopamine release) between the two
      experimental conditions in any of the brain regions of interest sampled. Our
      findings suggest that presentation of smoking cues does not elicit detectable (by
      PET) overall increases in dopamine in humans after one-hour nicotine abstinence.
      Future research should consider studying smoking cue-induced dopamine release at
      a longer abstinence period, since recent findings suggest the ability of smoking
      related cues to induce craving is associated with a longer duration of smoking
      abstinence.

PMID- 23555963
TI  - Deficient sumoylation of yeast 2-micron plasmid proteins Rep1 and Rep2 associated
      with their loss from the plasmid-partitioning locus and impaired plasmid
      inheritance.
AB  - The 2-micron plasmid of the budding yeast Saccharomyces cerevisiae encodes copy
      number amplification and partitioning systems that enable the plasmid to persist
      despite conferring no advantage to its host. Plasmid partitioning requires
      interaction of the plasmid Rep1 and Rep2 proteins with each other and with the
      plasmid-partitioning locus STB. Here we demonstrate that Rep1 stability is
      reduced in the absence of Rep2, and that both Rep proteins are sumoylated. Lysine
      to-arginine substitutions in Rep1 and Rep2 that inhibited their sumoylation
      perturbed plasmid inheritance without affecting Rep protein stability or two
      hybrid interaction between Rep1 and Rep2. One-hybrid and chromatin
      immunoprecipitation assays revealed that Rep1 was required for efficient
      retention of Rep2 at STB and that sumoylation-deficient mutants of Rep1 and Rep2
      were impaired for association with STB. The normal co-localization of both Rep
      proteins with the punctate nuclear plasmid foci was also lost when Rep1 was
      sumoylation-deficient. The correlation of Rep protein sumoylation status with
      plasmid-partitioning locus association suggests a theme common to eukaryotic
      chromosome segregation proteins, sumoylated forms of which are found enriched at
      centromeres, and between the yeast 2-micron plasmid and viral episomes that
      depend on sumoylation of their maintenance proteins for persistence in their
      hosts.

PMID- 23555964
TI  - Prevention of LPS-induced microglia activation, cytokine production and sickness
      behavior with TLR4 receptor interfering peptides.
AB  - The innate immune receptor Toll-like 4 (TLR4) is the receptor activated by
      lipopolysaccharide (LPS), and TLR4-LPS interaction is well known to induce an
      innate immune response, triggering sickness behavior. Within the brain, TLR4 is
      highly expressed in brain microglia, and excessive inflammation resulting from
      activation of this pathway in the brain has been implicated in depressive
      disorders and neurodegenerative pathologies. We hypothesized that blocking LPS
      induced activation of TLR4 would prevent downstream immune signaling in the brain
      and suppress the induction of sickness behavior. We used interfering peptides to
      block TLR4 activation and confirmed their efficacy in preventing second messenger
      activation and cytokine production normally induced by LPS treatment. Further,
      these peptides blocked morphological changes in microglia that are typically
      induced by LPS. We also demonstrated that intraperitoneal (i.p.) injection of Tat
      TLR4 interfering peptides prevented LPS-induced sickness behavior, as assessed in
      home cage behavior and with the intracranial self-stimulation paradigm. These
      newly synthesised peptides inhibit TLR4 signaling thereby preventing changes in
      behavior and motivation caused by inflammatory stimuli. These peptides highlight
      the roll of TLR4 and microglia morphology changes in sickness behavior, and thus
      may be of therapeutic value in limiting the deleterious impact of excessive
      inflammation in specific CNS pathologies.

PMID- 23555965
TI  - When celibacy matters: incorporating non-breeders improves demographic parameter
      estimates.
AB  - In long-lived species only a fraction of a population breeds at a given time. Non
      breeders can represent more than half of adult individuals, calling in doubt the
      relevance of estimating demographic parameters from the sole breeders. Here we
      demonstrate the importance of considering observable non-breeders to estimate
      reliable demographic traits: survival, return, breeding, hatching and fledging
      probabilities. We study the long-lived quasi-biennial breeding wandering
      albatross (Diomedea exulans). In this species, the breeding cycle lasts almost a
      year and birds that succeed a given year tend to skip the next breeding occasion
      while birds that fail tend to breed again the following year. Most non-breeders
      remain unobservable at sea, but still a substantial number of observable non
      breeders (ONB) was identified on breeding sites. Using multi-state capture-mark
      recapture analyses, we used several measures to compare the performance of
      demographic estimates between models incorporating or ignoring ONB: bias
      (difference in mean), precision (difference is standard deviation) and accuracy
      (both differences in mean and standard deviation). Our results highlight that
      ignoring ONB leads to bias and loss of accuracy on breeding probability and
      survival estimates. These effects are even stronger when studied in an age
      dependent framework. Biases on breeding probabilities and survival increased with
      age leading to overestimation of survival at old age and thus actuarial
      senescence and underestimation of reproductive senescence. We believe our study
      sheds new light on the difficulties of estimating demographic parameters in
      species/taxa where a significant part of the population does not breed every
      year. Taking into account ONB appeared important to improve demographic parameter
      estimates, models of population dynamics and evolutionary conclusions regarding
      senescence within and across taxa.

PMID- 23555966
TI  - The tolerogenic peptide, hCDR1, down-regulates the expression of interferon-alpha
      in murine and human systemic lupus erythematosus.
AB  - BACKGROUND: The tolerogenic peptide, hCDR1, ameliorated manifestations of
      systemic lupus erythematosus (SLE) via the immunomodulation of pro-inflammatory
      and immunosuppressive cytokines and the induction of regulatory T cells. Because
      type I interferon (IFN-alpha) has been implicated to play a role in SLE
      pathogenesis, we investigated the effects of hCDR1 on IFN-alpha in a murine model
      of SLE and in human lupus. METHODOLOGY PRINCIPAL FINDINGS: (NZBxNZW)F1 mice with
      established SLE were treated with hCDR1 (10 weekly injections). Splenocytes were
      obtained for gene expression studies by real-time RT-PCR. hCDR1 down-regulated
      significantly IFN-alpha gene expression (73% inhibition compared to vehicle
      treated mice, p = 0.002) in association with diminished clinical manifestations.
      Further, hCDR1 reduced, in vitro, IFN-alpha gene expression in peripheral blood
      mononuclear cells (PBMC) of 10 lupus patients (74% inhibition compared to medium,
      p = 0.002) but had no significant effects on the expression levels of IFN-alpha
      in PBMC of primary anti-phospholipid syndrome patients or of healthy controls.
      Lupus patients were treated for 24 weeks with hCDR1 (5) or placebo (4) by weekly
      subcutaneous injections. Blood samples collected, before and after treatment,
      were frozen until mRNA isolation. A significant reduction in IFN-alpha was
      determined in hCDR1 treated patients (64.4% inhibition compared to pretreatment
      expression levels, p = 0.015). No inhibition was observed in the placebo treated
      patients. In agreement, treatment with hCDR1 resulted in a significant decrease
      of disease activity. IFN-alpha appears to play a role in the mechanism of action
      of hCDR1 since recombinant IFN-alpha diminished the immunomodulating effects of
      hCDR1 on IL-1beta, TGFbeta and FoxP3 gene expression. CONCLUSIONS SIGNIFICANCE:
      We reported previously that hCDR1 affected various cell types and immune pathways
      in correlation to disease amelioration. The present studies demonstrate that
      hCDR1 is also capable of down-regulating significantly (and specifically to
      lupus) IFN-alpha gene expression. Thus, hCDR1 has a potential role as a novel,
      disease specific treatment for lupus.

PMID- 23555968
TI  - Actual ligation frequencies in the chromosome conformation capture procedure.
AB  - Chromosome conformation capture (3C) and derivative experimental procedures are
      used to estimate the spatial proximity between different genomic elements, thus
      providing information about the 3D organization of genomic domains and whole
      genomes within the nucleus. All C-methods are based on the proximity ligation-the
      preferential ligation of joined DNA fragments obtained upon restriction enzyme
      digestion of in vivo cross-linked chromatin. Here, using the mouse beta-globin
      genes in erythroid cells as a model, we estimated the actual frequencies of
      ligation between the fragments bearing the promoter of the major beta-globin gene
      and its distant enhancers and showed that the number of ligation products
      produced does not exceed 1% of all fragments subjected to the ligation. Although
      this low yield of 3C ligation products may be explained entirely by technical
      issues, it may as well reflect a low frequency of interaction between DNA
      regulatory elements in vivo.

PMID- 23555967
TI  - Amniotic fluid protein profiles of intraamniotic inflammatory response to
      Ureaplasma spp. and other bacteria.
AB  - OBJECTIVE: This study aimed to evaluate the amniotic fluid protein profiles and
      the intensity of intraamniotic inflammatory response to Ureaplasma spp. and other
      bacteria, using the multiplex xMAP technology. METHODS: A retrospective cohort
      study was undertaken in the Department of Obstetrics and Gynecology, University
      Hospital Hradec Kralove, Czech Republic. A total of 145 pregnant women with
      preterm prelabor rupture of membranes between gestational age 24+0 and 36+6 weeks
      were included in the study. Amniocenteses were performed. The presence of
      Ureaplasma spp. and other bacteria was evaluated using 16S rRNA gene sequencing.
      The levels of specific proteins were determined using multiplex xMAP technology.
      RESULTS: The presence of Ureaplasma spp. and other bacteria in the amniotic fluid
      was associated with increased levels of interleukin (IL)-6, IL-8, IL-10, brain
      derived neurotropic factor, granulocyte macrophage colony stimulating factor,
      monocyte chemotactic protein-1, macrophage inflammatory protein-1, and matrix
      metalloproteinasis-9. Ureaplasma spp. were also associated with increased levels
      of neurotropin-3 and triggering receptor expressed on myeloid cells-1.
      CONCLUSIONS: The presence of Ureaplasma spp. in the amniotic fluid is associated
      with a slightly different protein profile of inflammatory response, but the
      intensity of inflammatory response to Ureaplasma spp. is comparable with the
      inflammatory response to other bacteria.

PMID- 23555970
TI  - Predictors of mortality and differences in clinical features among patients with
      Cryptococcosis according to immune status.
AB  - INTRODUCTION: Cryptococcosis is an invasive fungal infection causing substantial
      morbidity and mortality. Prognostic factors are largely derived from trials
      conducted prior to the modern era of antifungal and potent combination
      antiretroviral therapies, immunosuppression, and transplantation. Data describing
      the clinical features and predictors of mortality in a modern cohort are needed.
      METHODS: We conducted a retrospective cohort study of patients at our institution
      diagnosed with cryptococcosis from 1996 through 2010. Data included demographics,
      clinical features, diagnostics, treatment, and outcomes. RESULTS: We identified
      302 individuals: 108 (36%) human immunodeficiency virus (HIV)-positive, 84 (28%)
      organ transplant recipients (OTRs), and 110 (36%) non-HIV, non-transplant (NHNT)
      patients including 39 with no identifiable immunodeficiency. Mean age was 49
      years, 203 (67%) were male and 170 (56%) were white. All-cause mortality at 90
      days was 21%. In multivariable logistic regression analyses, cryptococcemia (OR
      5.09, 95% CI 2.54-10.22) and baseline opening pressure >25 cmH2O (OR 2.93, 95% CI
      1.25-6.88) were associated with increased odds of mortality; HIV-positive
      patients (OR 0.46, 95% CI 0.19-1.16) and OTRs (OR 0.46, 95% CI 0.21-1.05) had
      lower odds of death compared to NHNT patients. CONCLUSIONS: Predictors of
      mortality from cryptococcosis in the modern period include cryptococcemia, high
      intracranial pressure, and NHNT status while drug(s) used for induction and
      historical prognostic factors including organ failure syndromes and hematologic
      malignancy were not associated with mortality.

PMID- 23555969
TI  - Molecular basis of live-attenuated influenza virus.
AB  - Human influenza is a seasonal disease associated with significant morbidity and
      mortality. The most effective means for controlling infection and thereby
      reducing morbidity and mortality is vaccination with a three inactivated
      influenza virus strains mixture, or by intranasal administration of a group of
      three different live attenuated influenza vaccine strains. Comparing to the
      inactivated vaccine, the attenuated live viruses allow better elicitation of a
      long-lasting and broader immune (humoral and cellular) response that represents a
      naturally occurring transient infection. The cold-adapted (ca) influenza
      A/AA/6/60 (H2N2) (AA ca) virus is the backbone for the live attenuated trivalent
      seasonal influenza vaccine licensed in the United States. Similarly, the
      influenza A components of live-attenuated vaccines used in Russia have been
      prepared as reassortants of the cold-adapted (ca) H2N2 viruses,
      A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47) along
      with virulent epidemic strains. However, the mechanism of temperature-sensitive
      attenuation is largely elusive. To understand how modification at genetic level
      of influenza virus would result in attenuation of human influenza virus A/PR/8/34
      (H1N1,A/PR8), we investigated the involvement of key mutations in the PB1 and/or
      PB2 genes in attenuation of influenza virus in vitro and in vivo. We have
      demonstrated that a few of residues in PB1 and PB2 are critical for the
      phenotypes of live attenuated, temperature sensitive influenza viruses by
      minigenome assay and real-time PCR. The information of these mutation loci could
      be used for elucidation of mechanism of temperature-sensitive attenuation and as
      a new strategy for influenza vaccine development.

PMID- 23555971
TI  - Determination of pneumococcal serotypes in meningitis cases in Niger, 2003-2011.
AB  - BACKGROUND: The epidemiology of pneumococcal meningitis in the African
      'meningitis belt' is poorly studied. In order to ensure an effective vaccination
      strategy and post-vaccination surveillance, we examined the serotype distribution
      patterns of pneumococcal meningitis in Niger over the period 2003-2011. METHODS:
      Cerebrospinal fluid (CSF) samples were collected from different health facilities
      throughout Niger in the frame of the national microbiological surveillance of
      meningitis. Determination of the serotype of CSF positive for pneumococci was
      performed using a sequential multiplex PCR method (SM-PCR) adapted with a
      national algorithm in which 32 different serotypes were covered and grouped into
      eight consecutive PCR. RESULTS: The SM-PCR assay could predict the Sp serotype
      for 779 CSF (88.7%), 98 CSF (11.3%) were not-typeable in our national-adapted
      algorithm. In total, 26 different serotypes were identified. Serotype 1 (n = 393)
      was the most prevalent and accounted for 45.3% of infections, followed by
      serogroups/serotypes 12F/(12A)/(44)/(46) (7.3%), 6/(6A/6B/6C/6D) (5.4%), 14
      (5.2%), 5 (4.6%), 23F (4.2%), 45 (3.6%), 2 (3.1%), 18/(18A/18B/18C/18F) (2.9%)
      and 17 others serotypes with a prevalence of less than 2%. The proportion of
      serotype 1 in infants(<2 years old) represented only 4.3% of the cases affected
      by this serotype. In contrast, serotypes 5, 6, 14, 19A and 23F were only detected
      in very young children. CONCLUSIONS: The proportion of serotype 1 in the
      pneumococcal meningitis cases and the theoretical vaccine coverage across all age
      groups advocates for the introduction of a conjugate vaccine (PCV10 or 13) into
      the Expanded Programme on Immunization (EPI) in Niger. Post-vaccine introduction
      surveillance supported by molecular approaches will be essential to provide a
      comprehensive picture of the impact of the vaccine on the burden reduction of
      pneumococcal meningitis and on pneumococcal serotype distribution.

PMID- 23555972
TI  - Genome-wide detection of selective signature in Chinese Holstein.
AB  - Selective signatures in whole genome can help us understand the mechanisms of
      selection and target causal variants for breeding program. In present study, we
      performed Extended Haplotype Homozygosity (EHH) tests to identify significant
      core regions harboring such signals in Chinese Holstein, and then verified the
      biological significance of these identified regions based on commonly-used
      bioinformatics analyses. Results showed a total of 125 significant regions in
      entire genome containing some of important functional genes such as LEP, ABCG2,
      CSN1S1, CSN3 and TNF based on the Gene Ontology database. Some of these annotated
      genes involved in the core regions overlapped with those identified in our
      previous GWAS as well as those involved in a recently constructed candidate gene
      database for cattle, further indicating these genes under positive selection
      maybe underlie milk production traits and other important traits in Chinese
      Holstein. Furthermore, in the enrichment analyses for the second level GO terms
      and pathways, we observed some significant terms over represented in these
      identified regions as compared to the entire bovine genome. This indicates that
      some functional genes associated with milk production traits, as reflected by GO
      terms, could be clustered in core regions, which provided promising evidence for
      the exploitability of the core regions identified by EHH tests. Findings in our
      study could help detect functional candidate genes under positive selection for
      further genetic and breeding research in Chinese Holstein.

PMID- 23555973
TI  - Gene mutation in microRNA target sites of CFTR gene: a novel pathogenetic
      mechanism in cystic fibrosis?
AB  - Cystic fibrosis (CF) is the most frequent lethal genetic disorder among
      Caucasians. It depends on alterations of a chloride channel expressed by most
      epithelial cells and encoded by CFTR gene. Also using scanning techniques to
      analyze the whole coding regions of CFTR gene, mutations are not identified in up
      to 10% of CF alleles, and such figure increases in CFTR-related disorders (CFTR
      RD). Other gene regions may be the site of causing-disease mutations. We searched
      for genetic variants in the 1500 bp of CFTR 3' untranslated region, typical
      target of microRNA (miRNA) posttranscriptional gene regulation, in either CF
      patients with the F508del homozygous genotype and different clinical expression
      (n = 20), CF (n = 32) and CFTR-RD (n = 43) patients with one or none mutation
      after CFTR scanning and in controls (n = 50). We identified three SNPs, one of
      which, the c.*1043A>C, was located in a region predicted to bind miR-433 and miR
      509-3p. Such mutation was peculiar of a CFTR-RD patient that had Congenital
      Bilateral Absence of Vas Deferens (CBAVD), diffuse bronchiectasis, a borderline
      sweat chloride test and the heterozygous severe F508del mutation on the other
      allele. The expression analysis demonstrated that the c.*1043A>C increases the
      affinity for miR-509-3p and slightly decreases that for the miR-433. Both miRNAs
      cause in vitro a reduced expression of CFTR protein. Thus, the c.*1043A>C may act
      as a mild CFTR mutation enhancing the affinity for inhibitory miRNAs as a novel
      pathogenetic mechanism in CF.

PMID- 23555974
TI  - Genetic variants from lipid-related pathways and risk for incident myocardial
      infarction.
AB  - BACKGROUND: Circulating lipids levels, as well as several familial lipid
      metabolism disorders, are strongly associated with initiation and progression of
      atherosclerosis and incidence of myocardial infarction (MI). OBJECTIVES: We
      hypothesized that genetic variants associated with circulating lipid levels would
      also be associated with MI incidence, and have tested this in three independent
      samples. SETTING AND SUBJECTS: Using age- and sex-adjusted additive genetic
      models, we analyzed 554 single nucleotide polymorphisms (SNPs) in 41 candidate
      gene regions proposed to be involved in lipid-related pathways potentially
      predisposing to incidence of MI in 2,602 participants of the Swedish Twin
      Register (STR; 57% women). All associations with nominal P<0.01 were further
      investigated in the Uppsala Longitudinal Study of Adult Men (ULSAM; N = 1,142).
      RESULTS: In the present study, we report associations of lipid-related SNPs with
      incident MI in two community-based longitudinal studies with in silico
      replication in a meta-analysis of genome-wide association studies. Overall, there
      were 9 SNPs in STR with nominal P-value <0.01 that were successfully genotyped in
      ULSAM. rs4149313 located in ABCA1 was associated with MI incidence in both
      longitudinal study samples with nominal significance (hazard ratio, 1.36 and
      1.40; P-value, 0.004 and 0.015 in STR and ULSAM, respectively). In silico
      replication supported the association of rs4149313 with coronary artery disease
      in an independent meta-analysis including 173,975 individuals of European descent
      from the CARDIoGRAMplusC4D consortium (odds ratio, 1.03; P-value, 0.048).
      CONCLUSIONS: rs4149313 is one of the few amino acid changing variants in ABCA1
      known to associate with reduced cholesterol efflux. Our results are suggestive of
      a weak association between this variant and the development of atherosclerosis
      and MI.

PMID- 23555975
TI  - Expression of blaA underlies unexpected ampicillin-induced cell lysis of
      Shewanella oneidensis.
AB  - Shewanella oneidensis is a facultative anaerobic gamma-proteobacterium possessing
      remarkably diverse respiratory capacities for reducing various organic and
      inorganic substrates. As a veteran research model for investigating redox
      transformations of environmental contaminants the bacterium is well known to be a
      naturally ampicillin-resistant microorganism. However, in this study we
      discovered that ampicillin has a significant impact on growth of S. oneidensis.
      Particularly, cell lysis occurred only with ampicillin at levels ranging from
      0.49 to 6.25 ug/ml but not at 50 ug/ml. This phenotype is attributable to
      insufficient expression of the beta-lactamase BlaA. The subsequent analysis
      revealed that the blaA gene is strongly induced by ampicillin at high (50 ug/ml),
      but not at low levels (2.5 ug/ml). In addition, we demonstrated that penicillin
      binding protein 5 (PBP5), the most abundant low molecular weight PBP (LMW PBP),
      is the only one relevant to beta-lactam resistance under the tested conditions.
      This nonessential PBP, largely resembling its Escherichia coli counterpart in
      functionality, mediates expression of the blaA gene.

PMID- 23555976
TI  - Mesenchymal stem cells engineered to inhibit complement-mediated damage.
AB  - Mesenchymal stem cells (MSC) preferentially migrate to damaged tissues and, due
      to their immunomodulatory and trophic properties, contribute to tissue repair.
      Although MSC express molecules, such as membrane cofactor protein (CD46),
      complement decay-accelerating factor (CD55), and protectin (CD59), which confer
      protection from complement-mediated lysis, MSC are recruited and activated by
      anaphylatoxins after transplantation, potentially causing MSC death and limiting
      therapeutic benefit. We have previously demonstrated that transduction of MSC
      with a retrovirus encoding HCMV-US proteins resulted in higher levels of MSC
      engraftment due to decreased HLA-I expression. Here, we investigate whether
      engineering MSC to express US2 (MSC-US2), US3 (MSC-US3), US6 (MSC-US6), or US11
      (MSC-US11) HCMV proteins can alter complement recognition, thereby better
      protecting MSC from complement attack and lysis. HCMV-US proteins increased MSC
      CD59 expression at different levels as determined by flow cytometric evaluation
      of the median fluorescence intensity ratio (MFI). A significant increase in CD59
      expression was seen in MSC-US2, MSC-US3, and MSC-US6, but not in MSC-US11. Only
      MSC-US2 displayed increased expression of CD46, while US2 and US3 proteins were
      both able to augment the percentage of MSC expressing this molecule. Regardless
      of the HCMV protein expressed, none changed CD55 MFI; however, expression of US6,
      US11, and US2 each increased the percentage of MSC that were positive for this
      molecule. Because US2 protein was the most efficient in up-regulating all three
      complement regulatory proteins, we used a functional complement-mediated
      cytotoxicity assay to investigate whether MSC-US2 were protected from complement
      mediated lysis. We demonstrated that over-expression of the US2 protein reduced
      complement lysis by 59.10+/-12.89% when compared to untransduced MSC. This is the
      first report, to our knowledge, describing a role of HCMV-US proteins in
      complement evasion, and our data shows that over-expression of US2 protein on MSC
      could serve as a strategy to protect these cells from complement lysis.

PMID- 23555977
TI  - Gene regulation by CcpA and catabolite repression explored by RNA-Seq in
      Streptococcus mutans.
AB  - A bacterial transcriptome of the primary etiological agent of human dental
      caries, Streptococcus mutans, is described here using deep RNA sequencing.
      Differential expression profiles of the transcriptome in the context of
      carbohydrate source, and of the presence or absence of the catabolite control
      protein CcpA, revealed good agreement with previously-published DNA microarrays.
      In addition, RNA-seq considerably expanded the repertoire of DNA sequences that
      showed statistically-significant changes in expression as a function of the
      presence of CcpA and growth carbohydrate. Novel mRNAs and small RNAs were
      identified, some of which were differentially expressed in conditions tested in
      this study, suggesting that the function of the S. mutans CcpA protein and the
      influence of carbohydrate sources has a more substantial impact on gene
      regulation than previously appreciated. Likewise, the data reveal that the
      mechanisms underlying prioritization of carbohydrate utilization are more diverse
      than what is currently understood. Collectively, this study demonstrates the
      validity of RNA-seq as a potentially more-powerful alternative to DNA microarrays
      in studying gene regulation in S. mutans because of the capacity of this approach
      to yield a more precise landscape of transcriptomic changes in response to
      specific mutations and growth conditions.

PMID- 23555978
TI  - Full and partial agonists of thromboxane prostanoid receptor unveil fine tuning
      of receptor superactive conformation and G protein activation.
AB  - The intrahelical salt bridge between E/D(3.49) and R(3.50) within the E/DRY motif
      on helix 3 (H3) and the interhelical hydrogen bonding between the E/DRY and
      residues on H6 are thought to be critical in stabilizing the class A G protein
      coupled receptors in their inactive state. Removal of these interactions is
      expected to generate constitutively active receptors. This study examines how
      neutralization of E(3.49/6.30) in the thromboxane prostanoid (TP) receptor alters
      ligand binding, basal, and agonist-induced activity and investigates the
      molecular mechanisms of G protein activation. We demonstrate here that a panel of
      full and partial agonists showed an increase in affinity and potency for E129V
      and E240V mutants. Yet, even augmenting the sensitivity to detect constitutive
      activity (CA) with overexpression of the receptor or the G protein revealed
      resistance to an increase in basal activity, while retaining fully the ability to
      cause agonist-induced signaling. However, direct G protein activation measured
      through bioluminescence resonance energy transfer (BRET) indicates that these
      mutants more efficiently communicate and/or activate their cognate G proteins.
      These results suggest the existence of additional constrains governing the shift
      of TP receptor to its active state, together with an increase propensity of these
      mutants to agonist-induced signaling, corroborating their definition as
      superactive mutants. The particular nature of the TP receptor as somehow
      "resistant" to CA should be examined in the context of its pathophysiological
      role in the cardiovascular system. Evolutionary forces may have favored
      regulation mechanisms leading to low basal activity and selected against more
      highly active phenotypes.

PMID- 23555979
TI  - Impact of influenza on health-related quality of life among confirmed (H1N1)2009
      patients.
AB  - BACKGROUND: We aimed to assess the changes in health-related quality of life
      (HRQL) in patients with confirmed diagnosis of influenza (H1N1)2009, and to
      estimate the individual and societal loss of quality-adjusted life years (QALYs)
      caused by the pandemic. METHODS AND RESULTS: Longitudinal study of patients
      recruited at major hospitals and primary care centers in Spain. Patients reported
      their HRQL (EQ-5D) during their influenza episode and seven days prior to it. A
      subsample was monitored to evaluate HRQL after recovery. HRQL loss was estimated
      as the difference between EQ-5D prior to the influenza episode and during it.
      Individual QALY loss (disutility multiplied by the duration of the influenza
      episode in days) for confirmed cases was calculated and used to estimate the
      societal loss in Spain (with the official estimations). A total of 432 inpatients
      and 563 outpatients were included, of whom 145 and 184, respectively, were
      followed up. Baseline mean HRQL loss was 0.58 (95% CI, 0.53-0.63) for inpatients
      and 0.43 (95% CI, 0.40-0.46) for outpatients. The majority of the 145 inpatients
      and 184 outpatients who were followed up regained initial HRQL levels, presenting
      a mean difference of 0.01 between the EQ-5D score prior to and after the
      influenza episode. Individual QALY losses for inpatients (0.031, 95% CI, 0.025
      0.037) were higher than for outpatients (0.009, 95% CI, 0.007-0.011), while
      societal QALY losses were reversed: 94 years for inpatients and 6,778 years for
      outpatients. For fatal cases (an official number of 318), we estimated a QALY
      loss of 11,981. CONCLUSIONS: The influenza (H1N1)2009 pandemic had a significant
      but temporary impact on the HRQL of the majority of confirmed in- and
      outpatients. The societal impact of the influenza pandemic in Spain was estimated
      to be higher than other acute conditions. These results provide useful data for
      future cost-utility analyses.

PMID- 23555980
TI  - High adherence to antimalarials and antibiotics under integrated community case
      management of illness in children less than five years in eastern Uganda.
AB  - BACKGROUND: Development of resistance to first line antimalarials led to
      recommendation of artemisinin based combination therapies (ACTs). High adherence
      to ACTs provided by community health workers (CHWs) gave reassurance that
      community based interventions did not increase the risk of drug resistance.
      Integrated community case management of illnesses (ICCM) is now recommended
      through which children will access both antibiotics and antimalarials from CHWs.
      Increased number of medicines has been shown to lower adherence. OBJECTIVE: To
      compare adherence to antimalarials alone versus antimalarials combined with
      antibiotics under ICCM in children less than five years. METHODS: A cohort study
      was nested within a cluster randomized trial that had CHWs treating children less
      than five years with antimalarials and antibiotics (intervention areas) and CHWs
      treating children with antimalarials only (control areas). Children were
      consecutively sampled from the CHWs' registers in the control areas (667
      children); and intervention areas (323 taking antimalarials only and 266 taking
      antimalarials plus antibiotics). The sampled children were visited at home on day
      one and four of treatment seeking. Adherence was assessed using self reports and
      pill counts. RESULTS: Adherence in the intervention arm to antimalarials alone
      and antimalarials plus antibiotics arm was similar (mean 99% in both groups) but
      higher than adherence in the control arm (antimalarials only) (mean 96%).
      Forgetfulness (38%) was the most cited reason for non-adherence. At adjusted
      analysis: absence of fever (OR = 3.3, 95%CI =1.6-6.9), seeking care after two or
      more days (OR = 2.2, 95%CI = 1.3-3.7), not understanding instructions given (OR =
      24.5, 95%CI = 2.7-224.5), vomiting (OR = 2.6, 95%CI = 1.2-5.5), and caregivers'
      perception that the child's illness was not severe (OR = 2.0, 95%CI = 1.1-3.8)
      were associated with non-adherence. CONCLUSIONS: Addition of antibiotics to
      antimalarials did not lower adherence. However, caregivers should be adequately
      counseled to understand the dosing regimens; continue with medicines even when
      the child seems to improve; and re-administer doses that have been vomited.

PMID- 23555981
TI  - Network connections that evolve to circumvent the inverse optics problem.
AB  - A fundamental problem in vision science is how useful perceptions and behaviors
      arise in the absence of information about the physical sources of retinal stimuli
      (the inverse optics problem). Psychophysical studies show that human observers
      contend with this problem by using the frequency of occurrence of stimulus
      patterns in cumulative experience to generate percepts. To begin to understand
      the neural mechanisms underlying this strategy, we examined the connectivity of
      simple neural networks evolved to respond according to the cumulative rank of
      stimulus luminance values. Evolved similarities with the connectivity of early
      level visual neurons suggests that biological visual circuitry uses the same
      mechanisms as a means of creating useful perceptions and behaviors without
      information about the real world.

PMID- 23555982
TI  - Long-term effect of bariatric surgery on liver enzymes in the Swedish Obese
      Subjects (SOS) study.
AB  - BACKGROUND AND AIM: Obesity is associated with elevated serum transaminase levels
      and non-alcoholic fatty liver disease and weight loss is a recommended
      therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining
      weight loss. Aim of the present study was to examine the long-term effects of
      bariatric surgery on transaminase levels in obese individuals. METHODS: The
      Swedish Obese Subjects (SOS) study is a prospective controlled intervention study
      designed to compare the long-term effects of bariatric surgery and usual care in
      obese subjects. A total of 3,570 obese participants with no excess of alcohol
      consumption at baseline (1,795 and 1,775 in the control and surgery group,
      respectively) were included in the analyses. Changes in transaminase levels
      during follow-up were compared in the surgery and control groups. RESULTS:
      Compared to usual care, bariatric surgery was associated with lower serum ALT and
      AST levels at 2- and 10- year follow up. The reduction in ALT levels was
      proportional to the degree of weight loss. Both the incidence of and the
      remission from high transaminase levels were more favorable in the surgery group
      compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was
      lower in the surgery compared to the control group at both 2- and 10-year follow
      up. CONCLUSIONS: Bariatric surgery results in a sustained reduction in
      transaminase levels and a long-term benefit in obese individuals.

PMID- 23555983
TI  - The importance of gender-stratified antibiotic resistance surveillance of
      unselected uropathogens: a Dutch Nationwide Extramural Surveillance study.
AB  - Few studies have been performed on urinary tract infections (UTIs) in men. In the
      present study, general practitioners (n = 42) from the Dutch Sentinel General
      Practice Network collected urinary samples from 560 male patients (>= 18 years)
      suspected of UTI and recorded prescribed antibiotic treatment. In this way, the
      antibiotic susceptibility of Gram-negative uropathogens, including extended
      spectrum beta-lactamase (ESBL-) producing Escherichia coli could be determined.
      In addition, E. coli susceptibility and antibiotic prescriptions were compared
      with data from a similar UTI study among women and with data collected 7 years
      earlier. Of 367 uropathogens (66%) identified (>= 10(3) cfu/mL), most were Gram
      negative (83%) and E. coli being isolated most frequently (51%). Antibiotic
      susceptibility to ciprofloxacin, norfloxacin and nitrofurantoin was 94%, 92% and
      88%, respectively, whereas co-amoxiclav (76%) and co-trimoxazole (80%) showed
      lower susceptibilities. One ESBL (0.5%) was found. A significantly higher
      proportion of female UTIs was caused by E. coli compared with men (72% versus
      51%, P<0.05). E. coli susceptibility tended to be lower in men compared with
      women, although not reaching statistical significance. No changes in E. coli
      susceptibility were observed over time (all P>0.05). Co-amoxiclav and
      nitrofurantoin prescriptions increased over time (11% versus 28% and 16% versus
      23% respectively, both P<0.05), whereas co-trimoxazole prescriptions decreased
      (24% versus 14%, P<0.05). In conclusion, given the observed gender differences in
      uropathogen distribution and (tendency in) E. coli antibiotic susceptibility,
      empirical male UTI treatment options should be based on surveillance studies
      including men only. When awaiting the culture result is clinically not possible,
      fluoroquinolones are advised as first-choice antibiotics for male UTIs in Dutch
      general practices based on current antibiotic susceptibility data. The prevalence
      of ESBL-producers was low and no differences were observed in antibiotic
      susceptibility over a 7-year period. In addition, antibiotic prescriptions
      changed in accordance with national guidelines during this time period.

PMID- 23555984
TI  - A novel balanced-lethal host-vector system based on glmS.
AB  - During the last decade, an increasing number of papers have described the use of
      various genera of bacteria, including E. coli and S. typhimurium, in the
      treatment of cancer. This is primarily due to the facts that not only are these
      bacteria capable of accumulating in the tumor mass, but they can also be
      engineered to deliver specific therapeutic proteins directly to the tumor site.
      However, a major obstacle exists in that bacteria because the plasmid carrying
      the therapeutic gene is not needed for bacterial survival, these plasmids are
      often lost from the bacteria. Here, we report the development of a balanced
      lethal host-vector system based on deletion of the glmS gene in E. coli and S.
      typhimurium. This system takes advantage of the phenotype of the GlmS(-) mutant,
      which undergoes lysis in animal systems that lack the nutrients required for
      proliferation of the mutant bacteria, D-glucosamine (GlcN) or N-acetyl-D
      glucosamine (GlcNAc), components necessary for peptidoglycan synthesis. We
      demonstrate that plasmids carrying a glmS gene (GlmS(+)p) complemented the
      phenotype of the GlmS(-) mutant, and that GlmS(+) p was maintained faithfully
      both in vitro and in an animal system in the absence of selection pressure. This
      was further verified by bioluminescent signals from GlmS (+)pLux carried in
      bacteria that accumulated in grafted tumor tissue in a mouse model. The signal
      was up to several hundred-fold stronger than that from the control plasmid, pLux,
      due to faithful maintenance of the plasmid. We believe this system will allow to
      package a therapeutic gene onto an expression plasmid for bacterial delivery to
      the tumor site without subsequent loss of plasmid expression as well as to
      quantify bioluminescent bacteria using in vivo imaging by providing a direct
      correlation between photon flux and bacterial number.

PMID- 23555985
TI  - Superiority of trans-oral over trans-nasal sampling in detecting Streptococcus
      pneumoniae colonization in adults.
AB  - The human nasopharynx is the main reservoir for Streptococcus pneumoniae. We
      applied conventional and molecular methods to determine the prevalence of S.
      pneumoniae nasopharyngeal colonization in adults. Paired trans-orally and trans
      nasally obtained nasopharyngeal samples from 268 parents of 24-month-old children
      were assessed for pneumococcal presence. Parents were classified as colonized
      when live pneumococci were recovered from either sample cultured on medium
      selective for S. pneumoniae. Of the 52 (19%) colonized parents 49 (18%) were
      culture-positive in trans-nasal and 10 (4%) in trans-oral samples. Bacterial
      growth was harvested from these cultures, DNA isolated and tested by quantitative
      PCR (qPCR) targeting lytA and piaA genes specific for S. pneumoniae. A sample was
      considered positive if signals for both genes were detected. Altogether 105 (39%)
      individuals were classified as positive for pneumococcus by qPCR including 50
      (19%) in trans-nasal and 94 (35%) in trans-oral settings. Although significantly
      more trans-nasal compared to trans-oral samples were culture-positive for S.
      pneumoniae at the primary diagnostic step (p<0.001) the opposite was observed in
      qPCR results (p<0.001). To confirm the presence of live pneumococcus in samples
      positive by qPCR but negative at the initial diagnostic step, we serially-diluted
      cell harvests, re-cultured and carefully examined for S. pneumoniae presence.
      Live pneumococci were recovered from an additional 43 parents including 42
      positive in trans-oral and 4 in trans-nasal samples increasing the number of
      individuals culture- and qPCR-positive to 93 (35%) and positive by either of two
      methods to 107 (40%). There were significantly more trans-oral than trans-nasal
      samples positive for pneumococcus by both culture and qPCR (n = 71; 27%; vs. n =
      50; 19%; p<0.05). Our data suggest that pneumococcal colonization is more common
      in adults than previously estimated and point towards the superiority of a trans
      oral over a trans-nasal approach when testing adults for colonization with S.
      pneumoniae.

PMID- 23555986
TI  - Matrix metalloproteinase-9 -1562C/T promoter polymorphism confers risk for COPD:
      a meta-analysis.
AB  - BACKGROUND: The role of matrix metalloproteinase (MMP) gene polymorphisms in the
      development of chronic obstructive pulmonary disease (COPD) has been reported
      with inconsistent results. This meta-analysis was performed to assess the
      association of MMP-1 -1607G/GG and MMP-9 -1562C/T promoter polymorphisms with
      COPD susceptibility. METHODS: Published case-control studies from Pubmed and
      China National Knowledge Infrastructure (CNKI) databases were retrieved. Data
      were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI)
      were calculated. RESULTS: A total of fourteen case-control studies were included
      in this meta-analysis. Pooled effect size showed an association of MMP-9 -1562
      C/T with the risk of COPD (dominant model: TT+CT vs CC; OR: 1.46; 95% CI: 1.02
      2.08; p = 0.04). However, no correlation with COPD was revealed in MMP-1 
      1607G/GG polymorphism. When stratified by ethnicity, results indicated MMP-1 
      1607G/GG (recessive model: G/G vs G/GG+GG/GG; OR: 1.20; 95% CI: 1.01-1.44; p =
      0.04) and MMP-9 -1562 C/T (dominant model; OR: 1.66; 95% CI: 1.01-2.71; p = 0.04)
      were correlated with COPD susceptibility among Caucasians and Asians
      respectively. According to source of controls, significant association of MMP-9 
      1562 C/T (additive model: T vs C; OR:1.71, 95% CI: 1.42-2.07; p<0.00001, and
      dominant model; OR: 1.92; 95% CI: 1.34-2.76; p = 0.0004) with COPD susceptibility
      was revealed in the subgroup with smoker-based controls. However, in the
      aforementioned risk estimates, only the association of MMP-9 -1562 C/T (additive
      and dominant models) with the risk of COPD in the subgroup with smoker-based
      controls persisted significantly after Bonferroni correction for multiple
      testing. Moreover, after excluding the studies without Hardy-Weinberg equilibrium
      and/or with small sample size, the pooled results were robust and no publication
      bias was found in this study. CONCLUSION: This meta-analysis suggests, when using
      healthy smokers as controls, MMP-9 -1562 C/T, but not MMP-1 -1607 G/GG
      polymorphism is associated with the risk of COPD.

PMID- 23555987
TI  - Effects of Biogents Sentinel Trap field placement on capture rates of adult Asian
      tiger mosquitoes, Aedes albopictus.
AB  - The Biogents(r) Sentinel (BGS) trap is the standard tool to monitor adult Aedes
      (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), the Asian tiger mosquito.
      BGS traps are commonly placed in residential properties during surveillance
      operations, but locations within properties may have significant differences in
      ambient light, temperature, and humidity (e.g. between a sunlit lawn and shady
      underbrush). We examined the effect of BGS trap placement on Ae. albopictus
      capture rates in three residential properties in Monmouth County, New Jersey,
      USA. In each property we visually selected locations as shade, partial shade, and
      sun. Traps in "partial shade" locations were under vegetation and were exposed to
      filtered sunlight during some parts of the day while "shaded" locations were
      never exposed to direct sunlight. Locations defined as "sun" were exposed to
      direct sunlight for large parts of the day. We placed a BGS trap in each of the
      three location types and used small data loggers to measure temperature, relative
      humidity, and light exposure at each trap during a 24-hour deployment. To address
      temporal variability, we made seven separate measurements from 31 August to 22
      September 2010. We found that "partial shade" and "full shade" locations did not
      differ but that "full sun" locations had significantly higher light exposure,
      higher temperature, and lower humidity. Importantly, Ae. albopictus catches
      (males, females, or both) were consistently and significantly over 3 times higher
      in traps located in shaded locations. To further investigate the effects of local
      temperature and humidity on surveillance we examined Ae. albopictus collections
      from 37 BGS traps fitted with data loggers and deployed weekly from August
      through mid October, during the 2009 season, in three urban sites in Mercer
      County, NJ. We confirmed that local climate influences capture rates and that Ae.
      albopictus surveillance projects need to monitor trap placement carefully for
      maximum efficiency.

PMID- 23555988
TI  - IRSp53 mediates podosome formation via VASP in NIH-Src cells.
AB  - Podosomes are cellular "feet," characterized by F-actin-rich membrane
      protrusions, which drive cell migration and invasion into the extracellular
      matrix. Small GTPases that regulate the actin cytoskeleton, such as Cdc42 and Rac
      are central regulators of podosome formation. The adaptor protein IRSp53 contains
      an I-BAR domain that deforms membranes into protrusions and binds to Rac, a CRIB
      motif that interacts with Cdc42, an SH3 domain that binds to many actin
      cytoskeletal regulators with proline-rich peptides including VASP, and the C
      terminal variable region by splicing. However, the role of IRSp53 and VASP in
      podosome formation had been unclear. Here we found that the knockdown of IRSp53
      by RNAi attenuates podosome formation and migration in Src-transformed NIH3T3
      (NIH-Src) cells. Importantly, the differences in the IRSp53 C-terminal splicing
      isoforms did not affect podosome formation. Overexpression of IRSp53 deletion
      mutants suggested the importance of linking small GTPases to SH3 binding
      partners. Interestingly, VASP physically interacted with IRSp53 in NIH-Src cells
      and was essential for podosome formation. These data highlight the role of IRSp53
      as a linker of small GTPases to VASP for podosome formation.

PMID- 23555989
TI  - Perineural mast cells are specifically enriched in pancreatic neuritis and
      neuropathic pain in pancreatic cancer and chronic pancreatitis.
AB  - BACKGROUND: Pancreatic neuritis is a histopathological hallmark of pancreatic
      neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic
      adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell
      subtypes that compose pancreatic neuritis and their correlation to the
      neuropathic pain syndrome in PCa and CP are yet unknown. METHODS: Inflammatory
      cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n
      = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte
      marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T
      helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase,
      PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain
      sensation. Perineural mast cell subtypes were analyzed by double immunolabeling
      with MC chymase. Expression and neural immunoreactivity of protease-activated
      receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and
      correlated to pain status of the patients. RESULTS: In PCa and CP, nerves were
      predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural
      inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%,
      CP: 27%). In both entities, neuropathic pain sensation was associated with a
      specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%;
      CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other
      inflammatory cell subtypes. The vast majority of these MC contained MC chymase.
      PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP
      patients. CONCLUSION: Pancreatic neuritis in PC and CP is composed of cytotoxic T
      lymphocytes, macrophages and MC. The specific enrichment of MC around
      intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the
      presence of MC-induced visceral hypersensitivity in the pancreas. Therefore,
      pancreatic and enteric neuropathies seem to share a similar type of neuro-immune
      interaction in the generation of visceral pain.

PMID- 23555990
TI  - Phosphorylated IkappaBalpha predicts poor prognosis in activated B-cell lymphoma
      and its inhibition with thymoquinone induces apoptosis via ROS release.
AB  - Activated B-cell lymphoma (ABC), one of the three subtypes of Diffuse Large B
      cell Lymphoma (DLBCL) has the worst survival rate after upfront chemotherapy and
      is characterized by constitutively activated NFkappaB. We therefore studied the
      role of NFkappaB In a cohort of clinical DLBCL samples and ABC cell lines. In our
      clinical tissue microarray cohort of DLBCL samples, p-IkappaBalpha was detected
      in 38.3% of ABC DLBCL and was an independent prognostic marker for poor survival.
      In vitro, we found that Thymoquinone (TQ), a natural compound isolated from
      Nigella sativa caused release of ROS in ABC cells. TQ-mediated release of ROS in
      turn inhibited NFkappaB activity by dephosphorylating IkappaBalpha and decreased
      translocation of p65 subunit of NFkappaB in the nuclear compartment in ABC cell
      lines. This led to inhibition of cell viability and induction of mitochondrial
      dependent apoptosis in ABC-DLBCL cell lines. Additionally, TQ treatment also
      caused up-regulation of death receptor 5 (DR5), however, up-regulation of DR5 did
      not play a role in TQ-induced apoptosis. Finally, combination of sub-optimal
      doses of TQ and TRAIL induced efficient apoptosis in ABC-DLBCL cell lines. These
      data show that p-IkappaBalpha can be used as a prognostic marker and target for
      therapy in this aggressive sub-type of DLBCL and TQ may play an important role in
      the management of DLBCL in the future.

PMID- 23555991
TI  - Dried plum's unique capacity to reverse bone loss and alter bone metabolism in
      postmenopausal osteoporosis model.
AB  - Interest in dried plum has increased over the past decade due to its promise in
      restoring bone and preventing bone loss in animal models of osteoporosis. This
      study compared the effects of dried plum on bone to other dried fruits and
      further explored the potential mechanisms of action through which dried plum may
      exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6
      mice were fed either a control diet or a diet supplemented with 25% (w/w) dried
      plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone
      mineral density improved in mice consuming the dried plum, apricot and grape
      diets compared to the OVX control mice, but dried plum was the only fruit to have
      an anabolic effect on trabecular bone in the vertebra and prevent bone loss in
      the tibia. Restoration of biomechanical properties occurred in conjunction with
      the changes in trabecular bone in the spine. Compared to other dried fruits in
      this study, dried plum was unique in its ability to down-regulate osteoclast
      differentiation coincident with up-regulating osteoblast and glutathione (GPx)
      activity. These alterations in bone metabolism and antioxidant status compared to
      other dried fruits provide insight into dried plum's unique effects on bone.

PMID- 23555992
TI  - Prognostic and predictive significance of MYC and KRAS alterations in breast
      cancer from women treated with neoadjuvant chemotherapy.
AB  - Breast cancer is a complex disease, with heterogeneous clinical evolution.
      Several analyses have been performed to identify the risk factors for breast
      cancer progression and the patients who respond best to a specific treatment. We
      aimed to evaluate whether the hormone receptor expression, HER2 and MYC genes and
      their protein status, and KRAS codon 12 mutations may be prognostic or predictive
      biomarkers of breast cancer. Protein, gene and mutation status were concomitantly
      evaluated in 116 breast tumors from women who underwent neoadjuvant chemotherapy
      with doxorubicin plus cyclophosphamide. We observed that MYC expression was
      associated with luminal B and HER2 overexpression phenotypes compared to luminal
      A (p<0.05). The presence of MYC duplication or polysomy 8, as well as KRAS
      mutation, were also associated with the HER2 overexpression subtype (p<0.05). MYC
      expression and MYC gain were more frequently observed in early-onset compared to
      late-onset tumors (p<0.05). KRAS mutation was a risk factor of grade 3 tumors
      (p<0.05). A multivariate logistic regression demonstrated that MYC amplification
      defined as MYC/nucleus ratio of >=2.5 was a protective factor for chemotherapy
      resistance. On the other hand, age and grade 2 tumors were a risk factor.
      Additionally, luminal B, HER2 overexpression, and triple-negative tumors
      presented increased odds of being resistant to chemotherapy relative to luminal A
      tumors. Thus, breast tumors with KRAS codon 12 mutations seem to present a worse
      prognosis. Additionally, MYC amplification may help in the identification of
      tumors that are sensitive to doxorubicin plus cyclophosphamide treatment. If
      confirmed in a large set of samples, these markers may be useful for clinical
      stratification and prognosis.

PMID- 23555993
TI  - Microevolutionary events involving narrow host plasmids influences local fixation
      of vancomycin-resistance in Enterococcus populations.
AB  - Vancomycin-resistance in enterococci (VRE) is associated with isolates within
      ST18, ST17, ST78 Enterococcus faecium (Efm) and ST6 Enterococcus faecalis (Efs)
      human adapted lineages. Despite of its global spread, vancomycin resistance rates
      in enterococcal populations greatly vary temporally and geographically. Portugal
      is one of the European countries where Tn1546 (vanA) is consistently found in a
      variety of environments. A comprehensive multi-hierarchical analysis of VRE
      isolates (75 Efm and 29 Efs) from Portuguese hospitals and aquatic surroundings
      (1996-2008) was performed to clarify the local dynamics of VRE. Clonal
      relatedness was established by PFGE and MLST while plasmid characterization
      comprised the analysis of known relaxases, rep initiator proteins and toxin
      antitoxin systems (TA) by PCR-based typing schemes, RFLP comparison,
      hybridization and sequencing. Tn1546 variants were characterized by PCR
      overlapping/sequencing. Intra- and inter-hospital dissemination of Efm ST18,
      ST132 and ST280 and Efs ST6 clones, carrying rolling-circle (pEFNP1/pRI1) and
      theta-replicating (pCIZ2-like, Inc18, pHTbeta-like, two pRUM-variants, pLG1-like,
      and pheromone-responsive) plasmids was documented. Tn1546 variants, mostly
      containing ISEf1 or IS1216, were located on plasmids (30-150 kb) with a high
      degree of mosaicism and heterogeneous RFLP patterns that seem to have resulted
      from the interplay between broad host Inc18 plasmids (pIP501, pRE25, pEF1), and
      narrow host RepA_N plasmids (pRUM, pAD1-like). TAs of Inc18 (omega-epsilon-zeta)
      and pRUM (Axe-Txe) plasmids were infrequently detected. Some plasmid chimeras
      were persistently recovered over years from different clonal lineages. This work
      represents the first multi-hierarchical analysis of VRE, revealing a frequent
      recombinatorial diversification of a limited number of interacting clonal
      backgrounds, plasmids and transposons at local scale. These interactions provide
      a continuous process of parapatric clonalization driving a full exploration of
      the local adaptive landscape, which might assure long-term maintenance of
      resistant clones and eventually fixation of Tn1546 in particular geographic
      areas.

PMID- 23555994
TI  - A bead aggregation assay for detection of low-affinity protein-protein
      interactions reveals interactions between N-terminal domains of inositol 1,4,5
      trisphosphate receptors.
AB  - Interactions between proteins are a hallmark of all cellular activities. Such
      interactions often occur with low affinity, a feature that allows them to be
      rapidly reversible, but it makes them difficult to detect using conventional
      methods such as yeast 2-hybrid analyses, co-immunoprecipitation or analytical
      ultracentrifugation. We developed a simple and economical bead aggregation assay
      to study low-affinity interactions between proteins. By coating beads with
      interacting proteins, the weak interactions between many proteins are sufficient
      to allow stable aggregation of beads, an avidity effect. The aggregation is
      easily measured to allow quantification of protein-protein interactions under a
      variety of controlled conditions. We use this assay to demonstrate low-affinity
      interactions between the N-terminal domains of an intracellular Ca(2+) channel,
      the type 1 inositol 1,4,5-trisphosphate receptor. This simple bead aggregation
      assay may have widespread application in the study of low-affinity interactions
      between macromolecules.

PMID- 23555995
TI  - A real-time impedance based method to assess Rhodococcus equi virulence.
AB  - Rhodococcus equi is a facultative intracellular pathogen of macrophages and the
      causative agent of foal pneumonia. R. equi virulence is usually assessed by
      analyzing intracellular growth in macrophages by enumeration of bacteria
      following cell lysis, which is time consuming and does not allow for a high
      throughput analysis. This paper describes the use of an impedance based real-time
      method to characterize proliferation of R. equi in macrophages, using virulent
      and attenuated strains lacking the vapA gene or virulence plasmid. Image analysis
      suggested that the time-dependent cell response profile (TCRP) is governed by
      cell size and roundness as well as cytoxicity of infecting R. equi strains. The
      amplitude and inflection point of the resulting TCRP were dependent on the
      multiplicity of infection as well as virulence of the infecting strain, thus
      distinguishing between virulent and attenuated strains.

PMID- 23555996
TI  - Diesel exhaust particles induce cysteine oxidation and s-glutathionylation in
      house dust mite induced murine asthma.
AB  - BACKGROUND: Diesel exhaust particle (DEP) exposure enhances allergic inflammation
      and has been linked to the incidence of asthma. Oxidative stress on the thiol
      molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host
      responses. The effect of DEP on the thiol oxidation/reduction (redox) state in
      the asthmatic lung is unknown. OBJECTIVE: To determine if DEP exposure alters the
      Cys or GSH redox state in the asthmatic airway. METHODS: Bronchoalveolar lavage
      fluid was obtained from a house dust mite (HDM) induced murine asthma model
      exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s
      glutathionylated cysteine (CySSG) were determined by high pressure liquid
      chromatography. RESULTS: DEP co-administered with HDM, but not DEP or HDM alone,
      decreased total Cys, increased CySS, and increased CySSG without significantly
      altering GSH or GSSG. CONCLUSIONS: DEP exposure promotes oxidation and S
      glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a
      novel mechanism by which DEP may enhance allergic inflammatory responses.

PMID- 23555997
TI  - The PAXgene((r)) tissue system preserves phosphoproteins in human tissue
      specimens and enables comprehensive protein biomarker research.
AB  - Precise quantitation of protein biomarkers in clinical tissue specimens is a
      prerequisite for accurate and effective diagnosis, prognosis, and personalized
      medicine. Although progress is being made, protein analysis from formalin-fixed
      and paraffin-embedded tissues is still challenging. In previous reports, we
      showed that the novel formalin-free tissue preservation technology, the PAXgene
      Tissue System, allows the extraction of intact and immunoreactive proteins from
      PAXgene-fixed and paraffin-embedded (PFPE) tissues. In the current study, we
      focused on the analysis of phosphoproteins and the applicability of two
      dimensional gel electrophoresis (2D-PAGE) and enzyme-linked immunosorbent assay
      (ELISA) to the analysis of a variety of malignant and non-malignant human
      tissues. Using western blot analysis, we found that phosphoproteins are
      quantitatively preserved in PFPE tissues, and signal intensities are comparable
      to that in paired, frozen tissues. Furthermore, proteins extracted from PFPE
      samples are suitable for 2D-PAGE and can be quantified by ELISA specific for
      denatured proteins. In summary, the PAXgene Tissue System reliably preserves
      phosphoproteins in human tissue samples, even after prolonged fixation or
      stabilization times, and is compatible with methods for protein analysis such as
      2D-PAGE and ELISA. We conclude that the PAXgene Tissue System has the potential
      to serve as a versatile tissue fixative for modern pathology.

PMID- 23555999
TI  - Transcriptomic analysis of Streptomyces coelicolor differentiation in solid
      sporulating cultures: first compartmentalized and second multinucleated mycelia
      have different and distinctive transcriptomes.
AB  - Streptomycetes are very important industrial bacteria, which produce two thirds
      of all clinically relevant secondary metabolites. They have a complex
      developmental-cycle in which an early compartmentalized mycelium (MI)
      differentiates to a multinucleated mycelium (MII) that grows inside the culture
      medium (substrate mycelium) until it starts to growth into the air (aerial
      mycelium) and ends up forming spores. Streptomyces developmental studies have
      focused mainly on the later stages of MII differentiation (aerial mycelium and
      sporulation), with regulation of pre-sporulation stages (MI/MII transition)
      essentially unknown. This work represents the first study of the Streptomyces MI
      transcriptome, analyzing how it differs from the MII transcriptome. We have used
      a very conservative experimental approach to fractionate MI from MII and quantify
      gene expressions. The expression of well characterized key
      developmental/metabolic genes involved in bioactive compound production
      (actinorhodin, undecylprodigiosin, calcium-dependent antibiotic, cpk, geosmin) or
      hydrophobic cover formation-sporulation (bld, whi, wbl, rdl, chp, ram) was
      correlated with MII differentiation. Additionally, 122 genes conserved in the
      Streptomyces genus, whose biological function had not been previously
      characterized, were found to be differentially expressed (more than 4-fold) in MI
      or MII. These genes encoded for putative regulatory proteins (transcriptional
      regulators, kinases), as well as hypothetical proteins. Knowledge about
      differences between the MI (vegetative) and MII (reproductive) transcriptomes
      represents a huge advance in Streptomyces biology that will make future
      experiments possible aimed at characterizing the biochemical pathways controlling
      pre-sporulation developmental stages and activation of secondary metabolism in
      Streptomyces.

PMID- 23555998
TI  - Arabidopsis DEAD-box RNA helicase UAP56 interacts with both RNA and DNA as well
      as with mRNA export factors.
AB  - The DEAD-box protein UAP56 (U2AF65-associcated protein) is an RNA helicase that
      in yeast and metazoa is critically involved in mRNA splicing and export. In
      Arabidopsis, two adjacent genes code for an identical UAP56 protein, and both
      genes are expressed. In case one of the genes is inactivated by a T-DNA
      insertion, wild type transcript level is maintained by the other intact gene. In
      contrast to other organisms that are severely affected by elevated UAP56 levels,
      Arabidopsis plants that overexpress UAP56 have wild type appearance. UAP56
      localises predominantly to euchromatic regions of Arabidopsis nuclei, and
      associates with genes transcribed by RNA polymerase II independently from the
      presence of introns, while it is not detected at non-transcribed loci.
      Biochemical characterisation revealed that in addition to ssRNA and dsRNA, UAP56
      interacts with dsDNA, but not with ssDNA. Moreover, the enzyme displays ATPase
      activity that is stimulated by RNA and dsDNA and it has ATP-dependent RNA
      helicase activity unwinding dsRNA, whereas it does not unwind dsDNA. Protein
      interaction studies showed that UAP56 directly interacts with the mRNA export
      factors ALY2 and MOS11, suggesting that it is involved in mRNA export from plant
      cell nuclei.

PMID- 23556000
TI  - Normal weight obesity is associated with metabolic syndrome and insulin
      resistance in young adults from a middle-income country.
AB  - OBJECTIVE: This population-based birth cohort study examined whether normal
      weight obesity is associated with metabolic disorders in young adults in a middle
      income country undergoing rapid nutrition transition. DESIGN AND METHODS: The
      sample involved 1,222 males and females from the 1978/79 Ribeirao Preto birth
      cohort, Brazil, aged 23-25 years. NWO was defined as body mass index (BMI) within
      the normal range (18.5-24.9 kg/m(2)) and the sum of subscapular and triceps
      skinfolds above the sex-specific 90th percentiles of the study sample. It was
      also defined as normal BMI and % BF (body fat) >23% in men and >30% in women.
      Insulin resistance (IR), insulin sensitivity and secretion were based on the
      Homeostasis Model Assessment (HOMA) model. RESULTS: In logistic models, after
      adjusting for age, sex and skin colour, NWO was significantly associated with
      Metabolic Syndrome (MS) according to the Joint Interim Statement (JIS) definition
      (Odds Ratio OR = 6.83; 95% Confidence Interval CI 2.84-16.47). NWO was also
      associated with HOMA2-IR (OR = 3.81; 95%CI 1.57-9.28), low insulin sensitivity
      (OR = 3.89; 95%CI 2.39-6.33), and high insulin secretion (OR = 2.17; 95%CI 1.24
      3.80). Significant associations between NWO and some components of the MS were
      also detected: high waist circumference (OR = 8.46; 95%CI 5.09-14.04), low High
      Density Lipoprotein cholesterol (OR = 1.65; 95%CI 1.11-2.47) and high
      triglyceride levels (OR = 1.93; 95%CI 1.02-3.64). Most estimates changed little
      after further adjustment for early and adult life variables. CONCLUSIONS: NWO was
      associated with MS and IR, suggesting that clinical assessment of excess body fat
      in normal-BMI individuals should begin early in life even in middle-income
      countries.

PMID- 23556001
TI  - Rapid immune colloidal gold strip for cetacean meat restraining illegal trade and
      consumption: implications for conservation and public health.
AB  - The consumption of cetacean meat is geographically common and often of
      undetermined sustainability. Besides, it can expose humans to contaminants and
      zoonotic pathogens. The illegality of possessing cetacean meat was likely under
      reported in some countries due to lack of attention paid by the officials
      although DNA analysis of market products helped to show such practices. We
      developed two monoclonal antibodies against synthetic peptides of myoglobin (Mb)
      for constructing a rapid immune colloidal gold strip. Only cetacean Mb is capable
      of binding to both antibodies and presents positive signal while the Mb from
      other animals can bind only 1 of the antibodies and presents negative result. The
      strip for cetacean meat would be an applicable and cost-effective test for field
      inspectors and even the general public. It contributes to increase the reporting
      capacity and coverage of illegal cetacean meat possession, which has implications
      for global cetacean conservation and public health.

PMID- 23556002
TI  - Protein phosphatase magnesium-dependent 1delta (PPM1D) mRNA expression is a
      prognosis marker for hepatocellular carcinoma.
AB  - BACKGROUND: Protein phosphatase magnesium-dependent 1delta (PPM1D) is an
      oncogene, overexpressed in many solid tumors, including ovarian cancer and breast
      cancer. The current study examined the expression and the prognostic value of
      PPM1D mRNA in human hepatocellular carcinoma (HCC). METHODS: Total RNA was
      extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA
      expression was determined by real-time quantitative reverse transcriptase
      polymerase chain reaction (qPCR). Immunohistochemistry assay was used to verify
      the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC
      patients were grouped according to PPM1D mRNA expression with the average PPM1D
      mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations
      between clinicopathologic variables, overall survival and PPM1D mRNA expression
      were analyzed. FINDINGS: PPM1D mRNA was significantly higher in HCC than in the
      paired non-cancerous tissue (p<0.01). This was confirmed by ppm1d staining. 56
      patients were classified as high expression group and the other 30 patients were
      categorized as low expression group. There were significant differences between
      the two groups in term of alpha-fetoprotein (alpha-FP) level (p<0.01), tumor size
      (p<0.01), TNM stage (p<0.01), recurrence incidence (p<0.01) and family history of
      liver cancer (p<0.01). The current study failed to find significant differences
      between the two groups in the following clinical characteristics: age, gender,
      portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV) infection and
      alcohol intake. Survival time of high expression group was significantly shorter
      than that of low expression group (median survival, 13 months and 32 months,
      respectively, p<0.01). CONCLUSION: Up-regulation of PPM1D mRNA was associated
      with progressive pathological feature and poor prognosis in HCC patients. PPM1D
      mRNA may serve as a prognostic marker in HCC.

PMID- 23556003
TI  - Toll-like receptor 2 and Toll-like receptor 4-dependent activation of B cells by
      a polysaccharide from marine fungus Phoma herbarum YS4108.
AB  - Various natural polysaccharides are capable of activating the immune system and
      therefore can be employed as biological response modifiers in anti-tumor therapy.
      We previously found a homogenous polysaccharide from the mycelium of marine
      fungus Phoma herbarum YS4108, named YCP, exhibiting strong in vivo antitumor
      ability via enhancement of the host immune responses. To further elucidate the
      role of YCP as a biological response modifier, the immunomodulating activities of
      YCP in B cells was investigated in the current study. We demonstrated that
      stimulation of YCP with murine splenic B cells resulted in cell proliferation and
      generation of IgM antibody response. Binding of YCP to B cells was a direct,
      saturable and reversible event and required TLR2 and TLR4 involvement. TLR2 and
      TLR4 defunctionalization by either antibody blocking or allele-specific mutation
      significantly impaired the B-cell proliferative and IgM responses to YCP. YCP
      interaction with TLR2 and TLR4 led to the activation of intracellular p38, ERK
      and JNK, as well as the translocation of transcriptional factor NF-kappaB into
      nucleus. Furthermore, specific inhibitors of p38, ERK, JNK and NF-kappaB could
      attenuate the ability of YCP to induce B cell proliferation and IgM production.
      Taken together, this study has indicated for the first time the immunostimulating
      properties of YCP on B cells through a receptor-mediated mechanism, which
      involves TLR2 and TLR4 and resultant activation of MAPK and NF-kappaB signaling
      pathways, thereby highlighting the role of YCP as an efficacious biological
      response modifier in oncologic immunotherapy.

PMID- 23556004
TI  - Differential hepatic metal and metallothionein levels in three Feral fish species
      along a metal pollution gradient.
AB  - The accumulation of cadmium, copper and zinc and the induction of
      metallothioneins (MT) in liver of three freshwater fish species was studied.
      Gudgeon (Gobio gobio), roach (Rutilus rutilus) and perch (Perca fluviatilis) were
      captured at 6 sampling sites along a cadmium and zinc gradient and one reference
      site in a tributary of the Scheldt River in Flanders (Belgium). At each site up
      to 10 individuals per species were collected and analyzed on their general
      condition factor (K), hepatosomatic index (HSI) and gonadosomatic index (GSI).
      From each individual fish the liver was dissected and analyzed on Cd, Cu and Zn
      and MT-content. Although not all species were present at each site, hepatic Cd
      and Zn levels generally followed the pollution gradient and highest levels were
      measured in perch, followed by roach and gudgeon. Nevertheless also an effect of
      site was observed on this order. MT-levels appeared to be the highest in gudgeon
      although differences with the other species were not very pronounced and depended
      on the site. Significant relationships were found between hepatic zinc
      accumulation and MT levels. For each species the ratio MT(theoretical)/
      MT(measured) was calculated, which gives an indication of the relative capacity
      to induce MTs and thus immobilize the metals. Perch had the lowest capacity in
      inducing MTs (highest ratio). Relationships between hepatic metal levels and fish
      condition indices were absent or very weak.

PMID- 23556005
TI  - Myocardial remodeling in diabetic cardiomyopathy associated with cardiac mast
      cell activation.
AB  - Diabetic cardiomyopathy is a specific disease process distinct from coronary
      artery disease and hypertension. The disease features cardiac remodeling
      stimulated by hyperglycemia of the left ventricle wall and disrupts contractile
      functions. Cardiac mast cells may be activated by metabolic byproducts resulted
      from hyperglycermia and then participate in the remodeling process by releasing a
      multitude of cytokines and bioactive enzymes. Nedocromil, a pharmacologic
      stabilizer of mast cells, has been shown to normalize cytokine levels and
      attenuate cardiac remodeling. In this study, we describe the activation of
      cardiac mast cells by inducing diabetes in normal mice using streptozotocin
      (STZ). Next, we treated the diabetic mice with nedocromil for 12 weeks and then
      examined their hearts for signs of cardiac remodeling and quantified contractile
      function. We observed significantly impaired heart function in diabetic mice, as
      well as increased cardiac mast cell density and elevated mast cell secretions
      that correlated with gene expression and aberrant cytokine levels associated with
      cardiac remodeling. Nedocromil treatment halted contractile dysfunction in
      diabetic mice and reduced cardiac mast cell density, which correlated with
      reduced bioactive enzyme secretions, reduced expression of extracellular matrix
      remodeling factors and collagen synthesis, and normalized cytokine levels.
      However, the results showed nedocromil treatments did not return diabetic mice to
      a normal state. We concluded that manipulation of cardiac mast cell function is
      sufficient to attenuate cardiomyopathy stimulated by diabetes, but other cellular
      pathways also contribute to the disease process.

PMID- 23556006
TI  - CISA: contig integrator for sequence assembly of bacterial genomes.
AB  - A plethora of algorithmic assemblers have been proposed for the de novo assembly
      of genomes, however, no individual assembler guarantees the optimal assembly for
      diverse species. Optimizing various parameters in an assembler is often performed
      in order to generate the most optimal assembly. However, few efforts have been
      pursued to take advantage of multiple assemblies to yield an assembly of high
      accuracy. In this study, we employ various state-of-the-art assemblers to
      generate different sets of contigs for bacterial genomes. A tool, named CISA, has
      been developed to integrate the assemblies into a hybrid set of contigs,
      resulting in assemblies of superior contiguity and accuracy, compared with the
      assemblies generated by the state-of-the-art assemblers and the hybrid assemblies
      merged by existing tools. This tool is implemented in Python and requires MUMmer
      and BLAST+ to be installed on the local machine. The source code of CISA and
      examples of its use are available at http://sb.nhri.org.tw/CISA/.

PMID- 23556007
TI  - Break Out: urogenital schistosomiasis and Schistosoma haematobium infection in
      the post-genomic era.

PMID- 23556008
TI  - Population migration: implications for lymphatic filariasis elimination
      programmes.
AB  - Human population migration is a common phenomenon in developing countries. Four
      categories of migration-endemic to nonendemic areas, rural to urban areas, non
      MDA areas to areas that achieved lymphatic filariasis (LF) control/elimination,
      and across borders-are relevant to LF elimination efforts. In many situations,
      migrants from endemic areas may not be able to establish active transmission foci
      and cause infection in local people in known nonendemic areas or countries. Urban
      areas are at risk of a steady inflow of LF-infected people from rural areas,
      necessitating prolonged intervention measures or leading to a prolonged "residual
      microfilaraemia phase." Migration-facilitated reestablishment of transmission in
      areas that achieved significant control or elimination of LF appears to be
      difficult, but such risk can not be excluded, particularly in areas with
      efficient vector-parasite combination. Transborder migration poses significant
      problems in some countries. Listing of destinations, in endemic and nonendemic
      regions/countries, and formulation of guidelines for monitoring the settlements
      and the infection status of migrants can strengthen the LF elimination efforts.

PMID- 23556009
TI  - S. haematobium as a common cause of genital morbidity in girls: a cross-sectional
      study of children in South Africa.
AB  - BACKGROUND: Schistosoma (S.) haematobium infection is a common cause of genital
      morbidity in adult women. Ova in the genital mucosal lining may cause lesions,
      bleeding, pain, discharge, and the damaged surfaces may pose a risk for HIV. In a
      heterogeneous schistosomiasis endemic area in South Africa, we sought to
      investigate if young girls had genital symptoms and if this was associated with
      urinary S. haematobium. METHODOLOGY: In a cross-sectional study of 18 randomly
      chosen primary schools, we included 1057 schoolgirls between the age of 10 and 12
      years. We interviewed assenting girls, whose parents had consented to their
      participation and examined three urines from each of them for schistosome ova.
      PRINCIPAL FINDINGS: One third of the girls reported to have a history of genital
      symptoms. Prior schistosomal infection was reported by 22% (226/1020), this was
      associated with current genital symptoms (p<0.001). In regression analysis the
      genital symptoms were significantly associated both with urinary schistosomiasis
      (p<0.001) and water contact (p<0.001). CONCLUSIONS: Even before sexually active
      age, a relatively large proportion of the participating girls had similar genital
      symptoms to those reported for adult genital schistosomiasis previously. Anti
      schistosomal treatment should be considered at a young age in order to prevent
      chronic genital damage and secondary infections such as HIV, sexually transmitted
      diseases and other super-infections.

PMID- 23556010
TI  - Systematic review and consensus guidelines for environmental sampling of
      Burkholderia pseudomallei.
AB  - BACKGROUND: Burkholderia pseudomallei, a Tier 1 Select Agent and the cause of
      melioidosis, is a Gram-negative bacillus present in the environment in many
      tropical countries. Defining the global pattern of B. pseudomallei distribution
      underpins efforts to prevent infection, and is dependent upon robust
      environmental sampling methodology. Our objective was to review the literature on
      the detection of environmental B. pseudomallei, update the risk map for
      melioidosis, and propose international consensus guidelines for soil sampling.
      METHODS/PRINCIPAL FINDINGS: An international working party (Detection of
      Environmental Burkholderia pseudomallei Working Party (DEBWorP)) was formed
      during the VIth World Melioidosis Congress in 2010. PubMed (January 1912 to
      December 2011) was searched using the following MeSH terms: pseudomallei or
      melioidosis. Bibliographies were hand-searched for secondary references. The
      reported geographical distribution of B. pseudomallei in the environment was
      mapped and categorized as definite, probable, or possible. The methodology used
      for detecting environmental B. pseudomallei was extracted and collated. We found
      that global coverage was patchy, with a lack of studies in many areas where
      melioidosis is suspected to occur. The sampling strategies and bacterial
      identification methods used were highly variable, and not all were robust. We
      developed consensus guidelines with the goals of reducing the probability of
      false-negative results, and the provision of affordable and 'low-tech'
      methodology that is applicable in both developed and developing countries.
      CONCLUSIONS/SIGNIFICANCE: The proposed consensus guidelines provide the basis for
      the development of an accurate and comprehensive global map of environmental B.
      pseudomallei.

PMID- 23556011
TI  - Accuracy of urine circulating cathodic antigen test for the diagnosis of
      Schistosoma mansoni in preschool-aged children before and after treatment.
AB  - BACKGROUND: The Kato-Katz technique is widely used for the diagnosis of
      Schistosoma mansoni, but shows low sensitivity in light-intensity infections. We
      assessed the accuracy of a commercially available point-of-care circulating
      cathodic antigen (POC-CCA) cassette test for the diagnosis of S. mansoni in
      preschool-aged children before and after praziquantel administration.
      METHODOLOGY: A 3-week longitudinal survey with a treatment intervention was
      conducted in Azaguie, south Cote d'Ivoire. Overall, 242 preschoolers (age range:
      2 months to 5.5 years) submitted two stool and two urine samples before
      praziquantel administration, and 86 individuals were followed-up posttreatment.
      Stool samples were examined with duplicate Kato-Katz thick smears for S. mansoni.
      Urine samples were subjected to POC-CCA cassette test for S. mansoni, and a
      filtration method for S. haematobium diagnosis. PRINCIPAL FINDINGS: Before
      treatment, the prevalence of S. mansoni, as determined by quadruplicate Kato
      Katz, single CCA considering 'trace' as negative (t-), and single CCA with
      'trace' as positive (t+), was 23.1%, 34.3% and 64.5%, respectively. Using the
      combined results (i.e., four Kato-Katz and duplicate CCA(t-)) as diagnostic
      'gold' standard, the sensitivity of a single Kato-Katz, a single CCA(t-) or
      CCA(t+) was 28.3%, 69.7% and 89.1%, respectively. Three weeks posttreatment, the
      sensitivity of a single Kato-Katz, single CCA(t-) and CCA(t+) was 4.0%, 80.0% and
      84.0%, respectively. The intensity of the POC-CCA test band reaction was
      correlated with S. mansoni egg burden (odds ratio = 1.2, p = 0.04).
      CONCLUSIONS/SIGNIFICANCE: A single POC-CCA cassette test appears to be more
      sensitive than multiple Kato-Katz thick smears for the diagnosis of S. mansoni in
      preschool-aged children before and after praziquantel administration. The POC-CCA
      cassette test can be recommended for the rapid identification of S. mansoni
      infections before treatment. Additional studies are warranted to determine the
      usefulness of POC-CCA for assessing drug efficacy and monitoring the impact of
      control interventions.

PMID- 23556012
TI  - Evidence of habitat structuring Aedes albopictus populations in Reunion Island.
AB  - Arbovirus vector dynamics and spread are influenced by climatic, environmental
      and geographic factors. Major Chikungunya and Dengue fever outbreaks occurring
      the last 10 years have coincided with the expansion of the mosquito vector Aedes
      albopictus to nearly all the continents. We characterized the ecological (larval
      development sites, population dynamics, insemination and daily survival rates)
      and genetic (diversity, gene flow, population structure) features of two Aedes
      albopictus populations from distinct environments (rural and urban) on Reunion
      Island, in the South-West Indian Ocean. Microsatellite analysis suggests
      population sub-structuring Ae. albopictus populations. Two genetic clusters were
      identified that were significantly linked to natural versus urban habitats with a
      mixed population in both areas. Ae. albopictus individuals prefer urban areas for
      mating and immature development, where hosts and containers that serve as larval
      development sites are readily available and support high population densities,
      whereas natural environments appear to serve as reservoirs for the mosquito.

PMID- 23556013
TI  - Activity of oxantel pamoate monotherapy and combination chemotherapy against
      Trichuris muris and hookworms: revival of an old drug.
AB  - BACKGROUND: It is widely recognized that only a handful of drugs are available
      against soil-transmitted helminthiasis, all of which are characterized by a low
      efficacy against Trichuris trichiura, when administered as single doses. The re
      evaluation of old, forgotten drugs is a promising strategy to identify
      alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We
      studied the activity of the veterinary drug oxantel pamoate against Trichuris
      muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In
      addition, the dose-effect of oxantel pamoate combined with albendazole,
      mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T.
      muris in vitro and additive or synergistic combinations were followed up in vivo.
      PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate
      against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate
      behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel
      pamoate combined with levamisole, albendazole or ivermectin using ratios based on
      their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27,
      respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel
      pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate
      (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus
      in vivo. CONCLUSION/SIGNIFICANCE: Our study confirms the excellent trichuricidal
      properties of oxantel pamoate. Since the drug lacks activity against hookworms it
      is necessary to combine oxantel pamoate with a partner drug with anti-hookworm
      properties. Synergistic effects were observed for oxantel pamoate-mebendazole,
      hence this combination should be studied in more detail. Since, of the standard
      drugs, albendazole has the highest efficacy against hookworms, additional
      investigations on the combination effect of oxantel pamoate-albendazole should be
      launched.

PMID- 23556014
TI  - A cell-surface phylome for African trypanosomes.
AB  - The cell surface of Trypanosoma brucei, like many protistan blood parasites, is
      crucial for mediating host-parasite interactions and is instrumental to the
      initiation, maintenance and severity of infection. Previous comparisons with the
      related trypanosomatid parasites T. cruzi and Leishmania major suggest that the
      cell-surface proteome of T. brucei is largely taxon-specific. Here we compare
      genes predicted to encode cell surface proteins of T. brucei with those from two
      related African trypanosomes, T. congolense and T. vivax. We created a cell
      surface phylome (CSP) by estimating phylogenies for 79 gene families with
      putative surface functions to understand the more recent evolution of African
      trypanosome surface architecture. Our findings demonstrate that the transferrin
      receptor genes essential for bloodstream survival in T. brucei are conserved in
      T. congolense but absent from T. vivax and include an expanded gene family of
      insect stage-specific surface glycoproteins that includes many currently
      uncharacterized genes. We also identify species-specific features and innovations
      and confirm that these include most expression site-associated genes (ESAGs) in
      T. brucei, which are absent from T. congolense and T. vivax. The CSP presents the
      first global picture of the origins and dynamics of cell surface architecture in
      African trypanosomes, representing the principal differences in genomic
      repertoire between African trypanosome species and provides a basis from which to
      explore the developmental and pathological differences in surface architectures.
      All data can be accessed at:
      http://www.genedb.org/Page/trypanosoma_surface_phylome.

PMID- 23556015
TI  - Transmission risks of schistosomiasis japonica: extraction from back-propagation
      artificial neural network and logistic regression model.
AB  - BACKGROUND: The transmission of schistosomiasis japonica in a local setting is
      still poorly understood in the lake regions of the People's Republic of China (P.
      R. China), and its transmission patterns are closely related to human, social and
      economic factors. METHODOLOGY/PRINCIPAL FINDINGS: We aimed to apply the
      integrated approach of artificial neural network (ANN) and logistic regression
      model in assessment of transmission risks of Schistosoma japonicum with
      epidemiological data collected from 2339 villagers from 1247 households in six
      villages of Jiangling County, P.R. China. By using the back-propagation (BP) of
      the ANN model, 16 factors out of 27 factors were screened, and the top five
      factors ranked by the absolute value of mean impact value (MIV) were mainly
      related to human behavior, i.e. integration of water contact history and
      infection history, family with past infection, history of water contact,
      infection history, and infection times. The top five factors screened by the
      logistic regression model were mainly related to the social economics, i.e.
      village level, economic conditions of family, age group, education level, and
      infection times. The risk of human infection with S. japonicum is higher in the
      population who are at age 15 or younger, or with lower education, or with the
      higher infection rate of the village, or with poor family, and in the population
      with more than one time to be infected. CONCLUSION/SIGNIFICANCE: Both BP
      artificial neural network and logistic regression model established in a small
      scale suggested that individual behavior and socioeconomic status are the most
      important risk factors in the transmission of schistosomiasis japonica. It was
      reviewed that the young population (<=15) in higher-risk areas was the main
      target to be intervened for the disease transmission control.

PMID- 23556016
TI  - Methodology of clinical trials aimed at assessing interventions for cutaneous
      leishmaniasis.
AB  - The current evidence-base for recommendations on the treatment of cutaneous
      leishmaniasis (CL) is generally weak. Systematic reviews have pointed to a
      general lack of standardization of methods for the conduct and analysis of
      clinical trials of CL, compounded with poor overall quality of several trials.
      For CL, there is a specific need for methodologies which can be applied
      generally, while allowing the flexibility needed to cover the diverse forms of
      the disease. This paper intends to provide clinical investigators with guidance
      for the design, conduct, analysis and report of clinical trials of treatments for
      CL, including the definition of measurable, reproducible and clinically
      meaningful outcomes. Having unified criteria will help strengthen evidence,
      optimize investments, and enhance the capacity for high-quality trials. The
      limited resources available for CL have to be concentrated in clinical studies of
      excellence that meet international quality standards.

PMID- 23556017
TI  - Analysis of Schistosomiasis haematobium infection prevalence and intensity in
      Chikhwawa, Malawi: an application of a two part model.
AB  - BACKGROUND: Urinary Schistosomiasis infection, a common cause of morbidity
      especially among children in less developed countries, is measured by the number
      of eggs per urine. Typically a large proportion of individuals are non-egg
      excretors, leading to a large number of zeros. Control strategies require better
      understanding of its epidemiology, hence appropriate methods to model infection
      prevalence and intensity are crucial, particularly if such methods add value to
      targeted implementation of interventions. METHODS: We consider data that were
      collected in a cluster randomized study in 2004 in Chikhwawa district, Malawi,
      where eighteen (18) villages were selected and randomised to intervention and
      control arms. We developed a two-part model, with one part for analysis of
      infection prevalence and the other to model infection intensity. In both parts of
      the model we adjusted for age, sex, education level, treatment arm, occupation,
      and poly-parasitism. We also assessed for spatial correlation in the model
      residual using variogram analysis and mapped the spatial variation in risk. The
      model was fitted using maximum likelihood estimation. RESULTS AND DISCUSSION: The
      study had a total of 1642 participants with mean age of 32.4 (Standard deviation:
      22.8), of which 55.4 % were female. Schistosomiasis prevalence was 14.2 %, with a
      large proportion of individuals (85.8 %) being non-egg excretors, hence zero
      inflated data. Our findings showed that S. haematobium was highly localized even
      after adjusting for risk factors. Prevalence of infection was low in males as
      compared to females across all the age ranges. S. haematobium infection increased
      with presence of co-infection with other parasite infection. Infection intensity
      was highly associated with age; with highest intensity in school-aged children (6
      to 15 years). Fishing and working in gardens along the Shire River were potential
      risk factors for S. haematobium infection intensity. Intervention reduced both
      infection intensity and prevalence in the intervention arm as compared to control
      arm. Farmers had high infection intensity as compared to non farmers, despite the
      fact that being a farmer did not show any significant association with
      probability of infection. These results evidently indicate that infection
      prevalence and intensity are associated with risk factors differently, suggesting
      a non-singular epidemiological setting. The dominance of agricultural, socio
      economic and demographic factors in determining S. haematobium infection and
      intensity suggest that disease transmission and control strategies should
      continue centring on improving socio-economic status, environmental modifications
      to control S. haematobium intermediate host snails and mass drug administration,
      which may be more promising approaches to disease control in high intensity and
      prevalence settings.

PMID- 23556018
TI  - Interruption of transmission of Onchocerca volvulus in the Southern Chiapas
      Focus, Mexico.
AB  - BACKGROUND: The Southern Chiapas focus of onchocerciasis in Southern Mexico
      represents one of the major onchocerciasis foci in Latin America. All 559 endemic
      communities of this focus have undergone semi-annual mass treatment with
      ivermectin since 1998. In 50 communities of this focus, ivermectin frequency
      shifted from twice to four times a year in 2003; an additional 113 communities
      were added to the quarterly treatment regimen in 2009 to achieve a rapid
      suppression of transmission. METHODOLOGY/PRINCIPAL FINDINGS: In-depth
      epidemiologic and entomologic assessments were performed in six sentinel
      communities (which had undergone 2 rounds of ivermectin treatment per year) and
      three extra-sentinel communities (which had undergone 4 rounds of ivermectin
      treatment per year). None of the 67,924 Simulium ochraceum s.l. collected from
      this focus during the dry season of 2011 were found to contain parasite DNA when
      tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR
      ELISA), resulting in an upper bound of the 95% confidence interval (95%-ULCI) of
      the infective rate in the vectors of 0.06/2,000 flies examined. Serological
      assays testing for Onchocerca volvulus exposure conducted on 4,230 children 5
      years of age and under (of a total population of 10,280 in this age group)
      revealed that 2/4,230 individuals were exposed to O. volvulus (0.05%; one sided
      95% confidence interval = 0.08%). CONCLUSIONS/SIGNIFICANCE: The in-depth
      epidemiological and entomological findings from the Southern Chiapas focus meet
      the criteria for interruption of transmission developed by the international
      community.

PMID- 23556019
TI  - Arginase activity - a marker of disease status in patients with visceral
      leishmaniasis in ethiopia.
AB  - The underlying mechanisms resulting in the profound immune suppression
      characteristic of human visceral leishmaniasis (VL) are not fully understood.
      Here, we tested the hypothesis that arginase, an enzyme associated with
      immunosuppression, is higher in patients with VL and contributes to impaired T
      cell responses. We recruited patients with VL before and after treatment and
      healthy controls and measured the arginase metabolism in the blood of these
      individuals. Our results show that arginase activity is significantly higher in
      the blood of patients with active VL as compared to controls. These high levels
      of arginase decline considerably once the patients are successfully treated. We
      identified the phenotype of arginase-expressing cells among PBMCs as neutrophils
      and show that their frequency was increased in PBMCs of patients before
      treatment; this coincides with reduced levels of L-arginine in the plasma and
      decreased expression levels of CD3zeta in T cells.

PMID- 23556020
TI  - Modulation of innate antigen-presenting cell function by pre-patent schistosome
      infection.
AB  - Schistosomes are intravascular helminths that infect over 200 million people
      worldwide. Deposition of eggs by adult schistosomes stimulates Th2 responses to
      egg antigens and induces granulomatous pathology that is a hallmark of
      schistosome infection. Paradoxically, schistosomes require host immune function
      for their development and reproduction and for egress of parasite eggs from the
      host. To identify potential mechanisms by which immune cells might influence
      parasite development prior to the onset of egg production, we assessed immune
      function in mice infected with developing schistosomes. We found that pre-patent
      schistosome infection is associated with a loss of T cell responsiveness to other
      antigens and is due to a diminution in the ability of innate antigen-presenting
      cells to stimulate T cells. Diminution of stimulatory capacity by schistosome
      worms specifically affected CD11b(+) cells and did not require concomitant
      adaptive responses. We could not find evidence for production of a diffusible
      inhibitor of T cells by innate cells from infected mice. Rather, inhibition of T
      cell responsiveness by accessory cells required cell contact and only occurred
      when cells from infected mice outnumbered competent APCs by more than 3?1.
      Finally, we show that loss of T cell stimulatory capacity may in part be due to
      suppression of IL-12 expression during pre-patent schistosome infection.
      Modulation of CD4(+) T cell and APC function may be an aspect of host immune
      exploitation by schistosomes, as both cell types influence parasite development
      during pre-patent schistosome infection.

PMID- 23556021
TI  - Chikungunya virus-associated long-term arthralgia: a 36-month prospective
      longitudinal study.
AB  - BACKGROUND: Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are
      responsible for acute fever and arthralgia, but can also lead to chronic
      symptoms. In 2006, a Chikungunya outbreak occurred in La Reunion Island, during
      which we constituted a prospective cohort of viremic patients (n = 180) and
      defined the clinical and biological features of acute infection. Individuals were
      followed as part of a longitudinal study to investigate in details the long-term
      outcome of Chikungunya. METHODOLOGY/PRINCIPAL FINDINGS: Patients were submitted
      to clinical investigations 4, 6, 14 and 36 months after presentation with acute
      CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients
      without arthralgia were randomly selected from the cohort and consented for blood
      sampling. During the 3 years following acute infection, 60% of patients had
      experienced symptoms of arthralgia, with most reporting episodic relapse and
      recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that
      were usually symmetrical (90%) and highly incapacitating (77%). They were often
      associated with local swelling (63%), asthenia (77%) or depression (56%). The age
      over 35 years and the presence of arthralgia 4 months after the disease onset are
      risk factors of long-term arthralgia. Patients with long-term arthralgia did not
      display biological markers typically found in autoimmune or rheumatoid diseases.
      These data helped define the features of CHIKV-associated chronic arthralgia and
      permitted an estimation of the economic burden associated with arthralgia.
      CONCLUSIONS/SIGNIFICANCE: This study demonstrates that chronic arthralgia is a
      frequent complication of acute Chikungunya disease and suggests that it results
      from a local rather than systemic inflammation.

PMID- 23556022
TI  - A role for eosinophils in the intestinal immunity against infective Ascaris suum
      larvae.
AB  - The aim of this study was to explore the mechanisms of resistance against
      invading Ascaris suum larvae in pigs. Pigs received a low dose of 100 A. suum
      eggs daily for 14 weeks. This resulted in a >99% reduction in the number of
      larvae that could migrate through the host after a challenge infection of 5000 A.
      suum eggs, compared to naive pigs. Histological analysis at the site of parasite
      entry, i.e. the caecum, identified eosinophilia, mastocytosis and goblet cell
      hyperplasia. Increased local transcription levels of genes for IL5, IL13,
      eosinophil peroxidase and eotaxin further supported the observed eosinophil
      influx. Further analysis showed that eosinophils degranulated in vitro in
      response to contact with infective Ascaris larvae in the presence of serum from
      both immune and naive animals. This effect was diminished with heat-inactivated
      serum, indicating a complement dependent mechanism. Furthermore, eosinophils were
      efficient in killing the larvae in vitro when incubated together with serum from
      immune animals, suggesting that A. suum specific antibodies are required for
      efficient elimination of the larvae. Together, these results indicate an
      important role for eosinophils in the intestinal defense against invading A. suum
      larvae.

PMID- 23556023
TI  - Biodiversity can help prevent malaria outbreaks in tropical forests.
AB  - BACKGROUND: Plasmodium vivax is a widely distributed, neglected parasite that can
      cause malaria and death in tropical areas. It is associated with an estimated 80
      300 million cases of malaria worldwide. Brazilian tropical rain forests encompass
      host- and vector-rich communities, in which two hypothetical mechanisms could
      play a role in the dynamics of malaria transmission. The first mechanism is the
      dilution effect caused by presence of wild warm-blooded animals, which can act as
      dead-end hosts to Plasmodium parasites. The second is diffuse mosquito vector
      competition, in which vector and non-vector mosquito species compete for blood
      feeding upon a defensive host. Considering that the World Health Organization
      Malaria Eradication Research Agenda calls for novel strategies to eliminate
      malaria transmission locally, we used mathematical modeling to assess those two
      mechanisms in a pristine tropical rain forest, where the primary vector is
      present but malaria is absent. METHODOLOGY/PRINCIPAL FINDINGS: The Ross-Macdonald
      model and a biodiversity-oriented model were parameterized using newly collected
      data and data from the literature. The basic reproduction number ([Formula: see
      text]) estimated employing Ross-Macdonald model indicated that malaria cases
      occur in the study location. However, no malaria cases have been reported since
      1980. In contrast, the biodiversity-oriented model corroborated the absence of
      malaria transmission. In addition, the diffuse competition mechanism was
      negatively correlated with the risk of malaria transmission, which suggests a
      protective effect provided by the forest ecosystem. There is a non-linear,
      unimodal correlation between the mechanism of dead-end transmission of parasites
      and the risk of malaria transmission, suggesting a protective effect only under
      certain circumstances (e.g., a high abundance of wild warm-blooded animals).
      CONCLUSIONS/SIGNIFICANCE: To achieve biological conservation and to eliminate
      Plasmodium parasites in human populations, the World Health Organization Malaria
      Eradication Research Agenda should take biodiversity issues into consideration.

PMID- 23556024
TI  - Novel insights into the genetic diversity of Balantidium and Balantidium-like
      cyst-forming ciliates.
AB  - Balantidiasis is considered a neglected zoonotic disease with pigs serving as
      reservoir hosts. However, Balantidium coli has been recorded in many other
      mammalian species, including primates. Here, we evaluated the genetic diversity
      of B. coli in non-human primates using two gene markers (SSrDNA and ITS1-5.8SDNA
      ITS2). We analyzed 49 isolates of ciliates from fecal samples originating from 11
      species of captive and wild primates, domestic pigs and wild boar. The
      phylogenetic trees were computed using Bayesian inference and Maximum likelihood.
      Balantidium entozoon from edible frog and Buxtonella sulcata from cattle were
      included in the analyses as the closest relatives of B. coli, as well as
      reference sequences of vestibuliferids. The SSrDNA tree showed the same
      phylogenetic diversification of B. coli at genus level as the tree constructed
      based on the ITS region. Based on the polymorphism of SSrDNA sequences, the type
      species of the genus, namely B. entozoon, appeared to be phylogenetically
      distinct from B. coli. Thus, we propose a new genus Neobalantidium for the
      homeothermic clade. Moreover, several isolates from both captive and wild
      primates (excluding great apes) clustered with B. sulcata with high support,
      suggesting the existence of a new species within this genus. The cysts of
      Buxtonella and Neobalantidium are morphologically indistinguishable and the
      presence of Buxtonella-like ciliates in primates opens the question about
      possible occurrence of these pathogens in humans.

PMID- 23556025
TI  - Parasitic zoonoses: one health surveillance in northern Saskatchewan.
AB  - We report the results of a joint human-animal health investigation in a Dene
      community in northern Saskatchewan, where residents harvest wildlife (including
      moose, bear, elk, and fish), live in close contact with free roaming dogs, and
      lack access to permanent veterinary services. Fecal analysis of owned and free
      roaming dogs over two consecutive years (N = 92, 103) identified several
      parasites of public health concern, including Toxocara canis, Diphyllobothrium
      spp., Echinococcus/Taenia, Cryptosporidium spp. and Giardia spp. Administration
      of pyrantel pamoate to a subset of dogs (N = 122) in the community in the first
      year was followed by reduced shedding of T. canis and other roundworms in the
      second year, demonstrating the potential utility of canine de-worming as a public
      health intervention. Using direct agglutination tests with confirmatory indirect
      fluorescent antibody test, 21% of 47 dogs were sero-positive for exposure to
      Toxoplasma gondii. Using enzyme-linked immunosorbent assay (ELISA) sero
      prevalence rates in 201 human volunteers were as follows: Toxoplasma gondii
      (14%), Echinococcus granulosus (48%), Toxocara canis (13%) and Trichinella spp.
      (16%). Overall 65% of participants were sero-positive for at least one parasite.
      A survey administered to volunteers indicated few associations between widely
      accepted risk factors for parasite exposure and serological status, emphasizing
      the importance of environmental transmission of these parasites through soil,
      food, and waterborne routes.

PMID- 23556026
TI  - The incidence of human cysticercosis in a rural community of Eastern Zambia.
AB  - A community-based longitudinal study was performed in the Eastern Province of
      Zambia, in which repeated serological samplings were done to determine the
      incidence of human cysticercosis. Three sampling rounds were carried out at six
      months intervals. A total of 867 participants presented for all three samplings.
      All samples were tested for the presence of cysticercus antigens using a
      monoclonal antibody-based enzyme-linked immunosorbent assay (sero-Ag-ELISA),
      while a randomly selected sub-sample of 161 samples from each sampling round was
      tested for specific antibodies using a commercial enzyme-linked
      immunoelectrotransfer blot (EITB) assay. Stool samples (n = 226) were also
      collected during the final round of sampling for taeniosis diagnosis by coprology
      and coproantigen ELISA. Cysticercosis seroprevalence varied from 12.2% to 14.5%
      (sero-Ag) and from 33.5% to 38.5% (sero-Ab) during the study period. A taeniosis
      prevalence of 11.9% was determined. Incidence rates of 6300 (sero-Ag, per 100000
      persons-year) and 23600 (sero-Ab, per 100000 persons-year) were determined.
      Seroreversion rates of 44% for sero-Ag and 38.7% for sero-Ab were recorded over
      the whole period. In conclusion, this study has shown the dynamic nature of T.
      solium infections; many of the people at risk become (re)infected due to the high
      environmental contamination, with a high number turning seronegative within a
      year after infection. An important number of infections probably never fully
      establish, leading to transient antibody responses and short-term antigen
      presence.

PMID- 23556027
TI  - Structure-activity relationship studies on the macrolide exotoxin mycolactone of
      Mycobacterium ulcerans.
AB  - BACKGROUND: Mycolactones are a family of polyketide-derived macrolide exotoxins
      produced by Mycobacterium ulcerans, the causative agent of the chronic
      necrotizing skin disease Buruli ulcer. The toxin is synthesized by polyketide
      synthases encoded by the virulence plasmid pMUM. The apoptotic, necrotic and
      immunosuppressive properties of mycolactones play a central role in the
      pathogenesis of M. ulcerans. METHODOLOGY/PRINCIPAL FINDINGS: We have synthesized
      and tested a series of mycolactone derivatives to conduct structure-activity
      relationship studies. Flow cytometry, fluorescence microscopy and Alamar Blue
      based metabolic assays were used to assess activities of mycolactones on the
      murine L929 fibroblast cell line. Modifications of the C-linked upper side chain
      (comprising C12-C20) caused less pronounced changes in cytotoxicity than
      modifications in the lower C5-O-linked polyunsaturated acyl side chain. A
      derivative with a truncated lower side chain was unique in having strong
      inhibitory effects on fibroblast metabolism and cell proliferation at non
      cytotoxic concentrations. We also tested whether mycolactones have antimicrobial
      activity and found no activity against representatives of Gram-positive
      (Streptococcus pneumoniae) or Gram-negative bacteria (Neisseria meningitis and
      Escherichia coli), the fungus Saccharomyces cerevisae or the amoeba Dictyostelium
      discoideum. CONCLUSION: Highly defined synthetic compounds allowed to
      unambiguously compare biological activities of mycolactones expressed by
      different M. ulcerans lineages and may help identifying target structures and
      triggering pathways.

PMID- 23556028
TI  - Case-control studies on the relationship between onchocerciasis and epilepsy:
      systematic review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis of all available case-control
      studies on the relationship between onchocerciasis and epilepsy. Because age and
      level of onchocerciasis endemicity in the area of residence are major
      determinants for infection, an additional analysis was performed, restricted to
      studies achieving control of these confounding factors. DATA SOURCES: Medical
      databases, the "African Neurology Database, Institute of Neuroepidemiology and
      Tropical Neurology, Limoges," reference lists of relevant articles, commercial
      search engines, up to May 2012. METHODS: We searched for studies examining
      infection status with Onchocerca volvulus in persons with epilepsy (PWE) and
      without epilepsy (PWOE) providing data suitable for the calculation of pooled
      odds ratios (ORp) and/or standardized mean differences (SMD) using random-effects
      models. RESULTS: Eleven studies providing data of qualitative skin biopsies for
      diagnosis of onchocerciasis were identified. Combined analysis on the total
      sample of 876 PWE and 4712 PWOE resulted in an ORp of 2.49 (95% confidence
      interval (95%CI): 1.61-3.86, p<0.001). When this analysis was restricted to those
      studies achieving control for age, residence and sex (367 PWE, 624 PWOE), an ORp
      of 1.29 (95% CI: 0.93-1.79; p = 0.139) was found. Presence of nodules for
      diagnosis of onchocerciasis was analyzed in four studies (225 PWE, 189 PWOE; ORp
      1.74; 95%CI: 0.94-3.20; p<0.076), including two studies of the restricted
      analysis (106 PWE, 106 PWOE; ORp 2.81; 95%CI: 1.57-5.00; p<0.001). One study
      examined quantitative microfilariae counts in patients without preceding
      microfilaricidal treatment and demonstrated significantly higher counts in PWE
      than in PWOE. INTERPRETATION: Our results strengthen the hypothesis that, in
      onchocerciasis foci, epilepsy and infection with O. volvulus are associated.
      Analysis of indicators giving information on infection intensity, namely nodule
      palpation and quantitative microfilaria count in untreated patients, support the
      hypothesis that intensity of infection with O. volvulus is involved in the
      etiology of epilepsy.

PMID- 23556029
TI  - Rapidly boosted Plasma IL-5 induced by treatment of human Schistosomiasis
      haematobium is dependent on antigen dose, IgE and eosinophils.
AB  - BACKGROUND: IgE specific to worm antigen (SWA) and pre-treatment eosinophil
      number, are associated with human immunity to re-infection with schistosomes
      after chemotherapeutic treatment. Treatment significantly elevates circulating IL
      5 24-hr post-treatment of Schistosoma mansoni. Here we investigate if
      praziquantel treatment of human schistosomiasis haematobium also boosts
      circulating IL-5, the immunological and parasitological factors that predispose
      to this, and the relationship between these and subsequent immunity to post
      treatment re-infection. METHODOLOGY/PRINCIPLE FINDINGS: The relationship between
      pre-treatment SWA-IgE, eosinophil number and infection intensity and the 24-hr
      post-treatment IL-5 boost was investigated in a Malian cohort (aged 5-40 yrs),
      exposed to S. haematobium. Eotaxin levels were measured at 24-hr post-treatment
      as a proxy of eosinophil migration. The relationship between the 24-hr post
      treatment IL-5 boost and later eosinophil numbers and SWA-IgE levels (9-wk post
      treatment) was examined, then investigated in the context of subsequent levels of
      re-infection (2-yr post-treatment). Circulating IL-5 levels increased 24-hr post
      treatment and were associated with pre-treatment infection intensity, SWA-IgE
      levels, eosinophil number, as well as 24-hr post-treatment eotaxin levels. 24-hr
      IL-5 levels were, in turn, significantly associated with eosinophil number and
      elevated SWA-IgE 9-wk later. These SWA-IgE levels were significantly associated
      with immunity to re-infection. CONCLUSIONS/SIGNIFICANCE: Early IL-5 production
      after treatment-induced exposure to S. haematobium worm antigen is positively
      associated with antigen dose (infection intensity), IgE availability for arming
      of effector cells at time of treatment and subsequent eosinophil migration
      response (as indicated by eotaxin levels). The IL-5 produced is positively
      associated with increased downstream eosinophil number and increases in specific
      IgE levels, implicating this cytokine boost and its down-stream consequences in
      the production and maintenance of IgE, and subsequent re-infection immunity.

PMID- 23556030
TI  - A Wolbachia wMel transinfection in Aedes albopictus is not detrimental to host
      fitness and inhibits Chikungunya virus.
AB  - BACKGROUND: Wolbachia inherited intracellular bacteria can manipulate the
      reproduction of their insect hosts through cytoplasmic incompatibility (CI), and
      certain strains have also been shown to inhibit the replication or dissemination
      of viruses. Wolbachia strains also vary in their relative fitness effects on
      their hosts and this is a particularly important consideration with respect to
      the potential of newly created transinfections for use in disease control.
      METHODOLOGY/PRINCIPAL FINDINGS: In Aedes albopictus mosquitoes transinfected with
      the wMel strain from Drosophila melanogaster, which we previously reported to be
      unable to transmit dengue in lab challenges, no significant detrimental effects
      were observed on egg hatch rate, fecundity, adult longevity or male mating
      competitiveness. All these parameters influence the population dynamics of
      Wolbachia, and the data presented are favourable with respect to the aim of
      taking wMel to high population frequency. Challenge with the chikungunya (CHIKV)
      virus, for which Ae. albopictus is an important vector, was conducted and the
      presence of wMel abolished CHIKV dissemination to the saliva.
      CONCLUSIONS/SIGNIFICANCE: Taken together, these data suggest that introducing
      wMel into natural Ae. albopictus populations using bidirectional CI could be an
      efficient strategy for preventing or reducing the transmission of arboviruses by
      this species.

PMID- 23556031
TI  - In Vivo c-Met Pathway Inhibition Depletes Human Glioma Xenografts of Tumor
      Propagating Stem-Like Cells.
AB  - Solid malignancies contain sphere-forming stem-like cells that are particularly
      efficient in propagating tumors. Identifying agents that target these cells will
      advance the development of more effective therapies. Recent converging evidence
      shows that c-Met expression marks tumor-initiating stem-like cells and that c-Met
      signaling drives human glioblastoma multiforme (GBM) cell stemness in vitro.
      However, the degree to which tumor-propagating stem-like cells depend on c-Met
      signaling in histologically complex cancers remains unknown. We examined the
      effects of in vivo c-Met pathway inhibitor therapy on tumor-propagating stem-like
      cells in human GBM xenografts. Animals bearing pre-established tumor xenografts
      expressing activated c-Met were treated with either neutralizing anti- hepatocyte
      growth factor (HGF) monoclonal antibody L2G7 or with the c-Met kinase inhibitor
      PF2341066 (Crizotinib). c-Met pathway inhibition inhibited tumor growth, depleted
      tumors of sphere-forming cells, and inhibited tumor expression of stem cell
      markers CD133, Sox2, Nanog, and Musashi. Withdrawing c-Met pathway inhibitor
      therapy resulted in a substantial rebound in stem cell marker expression
      concurrent with tumor recurrence. Cells derived from xenografts treated with anti
      HGF in vivo were depleted of tumor-propagating potential as determined by in vivo
      serial dilution tumor-propagating assay. Furthermore, daughter xenografts that
      did form were 12-fold smaller than controls. These findings show that stem-like
      tumor-initiating cells are dynamically regulated by c-Met signaling in vivo and
      that c-Met pathway inhibitors can deplete tumors of their tumor-propagating stem
      like cells.

PMID- 23556032
TI  - Efinaconazole 10% solution: a new topical treatment for onychomycosis: contact
      sensitization and skin irritation potential.
AB  - BACKGROUND: Onychomycosis is a chronic condition that often requires long-term
      management to eradicate the causative fungus, allow a healthy nail to grow, and
      prevent relapse. As a successful outcome depends highly on patient adherence with
      treatment, a low risk of periungual skin irritation with topical medication is
      clinically relevant. OBJECTIVES: To study the potential for efinaconazole 10%
      solution and its corresponding vehicle to induce delayed contact skin
      sensitization and evaluate its skin irritation potential. METHODS: Efinaconazole
      10% solution and its vehicle were studied in 239 healthy volunteers for the
      potential to induce contact skin sensitization. This included a series of
      induction, challenge, and re-challenge phases. An additional 21-day cumulative
      irritation study was undertaken in 35 healthy volunteers to compare three
      concentrations of efinaconazole (1%, 5%, and 10%), vehicle, and positive/negative
      controls. RESULTS: There was no evidence of induced contact sensitization under
      occlusive, semi-occlusive, and open (open rub-in) applications of efinaconazole
      10% solution. Efinaconazole 1%, 5%, and 10% solutions have mean cumulative
      irritancy indices of 1.12, 1.26, and 1.18, respectively, where a range of >0 to
      <=1 is classified as "mildly irritating." RESULTS were comparable to vehicle
      (1.04). CONCLUSION: Efinaconazole 10% solution did not cause contact
      sensitization and induced only minimal skin irritation in the studies completed.

PMID- 23556033
TI  - A method for working with displeased patients-blast.
AB  - Clinicians inevitably encounter patients with complaints and concerns about the
      quality of their care. This causes some to experience anxiety, fear, anger,
      resentment, guilt, and depression, especially when they believe they may have
      erred or caused harm. Lack of customer-service training and experience may
      contribute to these emotions. The "BLAST" technique is a complaint-resolution
      method that is useful in patient care and as a clinical teaching tool. The
      mnemonic stands for: Believe (what the patient is saying), Listen (actively, to
      assess and restate the patient's unmet expectations), Apologize (for the
      patient's unmet expectations), Satisfy (the patient), and Thank (the patient for
      expressing his/her concerns and providing a second chance to satisfy the
      patient). The technique appears to help clinicians become more at ease and
      confident when handling patient complaints. This may be especially helpful for
      clinicians who must routinely interact with post-treatment and post-procedure
      patients who commonly express surprise, concern, or complaints about their
      results and healing. BLAST may be an effective teaching tool enabling students,
      residents, and clinicians to become more comfortable and adept at working with
      displeased and concerned patients.

PMID- 23556035
TI  - Urticaria multiforme.
AB  - Urticaria multiforme is a benign cutaneous hypersensitivity reaction seen in
      pediatric patients that is characterized by the acute and transient onset of
      blanchable, annular, polycyclic, erythematous wheals with dusky, ecchymotic
      centers in association with acral edema. It is most commonly misdiagnosed as
      erythema multiforme, a serum-sickness-like reaction, or urticarial vasculitis.
      Since these three diagnoses represent distinct clinical entities with unique
      prognoses and management strategies, it is important that physicians distinguish
      urticaria multiforme from its clinical mimics in order to optimize patient care.
      By performing a thorough history and physical examination, the astute clinician
      can make the correct diagnosis and develop an appropriate, effective treatment
      plan while avoiding unnecessary biopsies and laboratory evaluations. The authors
      report a case of urticaria multiforme in a four-year-old girl in order to
      emphasize the distinctive morphological manifestations of this rare, albeit
      unique, disease seen in the pediatric population.

PMID- 23556034
TI  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy (CADASIL).
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephelopathy is an autosomal dominant disease affecting small vessels and
      often resulting in subcortical infarcts. A skin biopsy may facilitate its
      diagnosis as the cutaneous surface is much easier to sample than the central
      nervous system's tissue. Unfortunately, there is no effective treatment available
      today.

PMID- 23556036
TI  - Amyopathic dermatomyositis complicated by pneumomediastinum.
AB  - Dermatomyositis is an inflammatory disease of unclear etiology with
      characteristic cutaneous and musculoskeletal findings. Amyopathic dermatomyositis
      is a subtype without musculoskeletal involvement. Many cases of dermatomyositis
      are associated with underlying malignancy, but pulmonary manifestations can also
      be seen, the most common of which is interstitial lung disease. Pneumomediastinum
      is a rare complication that is important for clinicians to recognize, as it may
      be fatal if left untreated. The sudden onset of facial edema and shortness of
      breath in the setting of dermatomyositis should raise the suspicion of this
      condition.

PMID- 23556037
TI  - Fluconazole-induced Fixed Drug Eruption.
AB  - Triazole antifungals are commonly used in the treatment of oral, esophageal, and
      vaginal candidiasis. Fluconazole is frequently prescribed as the therapy modality
      for vaginal fungal infections. On rare occasions, fluconazole has been shown to
      cause fixed drug eruptions. Lesions of fixed drug eruptions vary in size and
      number, but have the same general appearance and symptoms. The authors report a
      case of fluconazole-induced fixed drug eruption in a 24-year-old woman with
      recurrent vaginal candidiasis. The lesion was initially diagnosed as a spider
      bite. Topical and oral provocation tests with fluconazole were performed. Topical
      provocation with petroleum/fluconazole and dimethyl sulfoxide/fluonazole were
      both negative. Oral provocation was positive, thus confirming the diagnosis of
      fluconazole-induced fixed drug eruption.

PMID- 23556038
TI  - Indurated plaques and nodules on the buttocks of a young healthy female.

PMID- 23556039
TI  - A study of the effects of saliva stimulation by nizatidine on dry mouth symptoms
      of primary biliary cirrhosis.
AB  - AIM: To elucidate the effect of saliva stimulation by nizatidine on oral symptoms
      of primary biliary cirrhosis (PBC) by administering it to PBC cases. METHODS:
      From among 73 cases that had been definitively diagnosed as PBC at our hospital
      by February 2010, we selected 27 cases of PBC, 4 males and 23 females, as
      subjects. We obtained subjects' consent after giving them a full explanation of
      the administration of nizatidine. Nizatidine 150 mg was administered internally
      twice daily, after morning and evening meals. To observe changes in the quantity
      of saliva secreted, chewing gum tests were carried out four times: before the
      initial dose, and after 6 mo, 12 mo and 24 mo of administration. For subjective
      dry mouth symptoms, a visual analog scale (VAS) method was used to assess their
      feelings of oral dryness and eating difficulty, five times: before the initial
      dose, and after 1, 6, 12 and 24 mo of administration in 8 cases. The nutritional
      condition and the hepatic functional reserve were compared between before and
      after the nizatidine treatment. RESULTS: The result of a chewing gum test on the
      subjects before the administration of nizatidine showed that 50% produced less
      than 10 mL of saliva, i.e., the standard under which cases are considered to have
      hyposalivation. The results of these tests showed that the quantity of saliva
      secreted was 10.5 +/- 6.8 mL before administration of nizatidine, 10.9 +/- 6.0 mL
      after 6 mo, 10.6 +/- 4.9 mL after 12 mo, and 11.8 +/- 6.8 mL after 24 mo
      administration. Thus, there was a slowly increasing trend in the quantity of
      saliva in the whole group. The percentage of subjects with saliva production
      above 10 mL was 45.8% after 6 mo administration of nizatidine, that is, only a
      slight change from before its administration, but it was 64.3% after 12 mo, that
      is, a significant increase. The saliva secretion by subject patients was examined
      before the beginning of administration of nizatidine, 12 mo later, and 24 mo
      later, and Fisher's combined probability test was used to examine the results for
      increases in saliva secretion. The analysis yielded P values of 0.51 and 0.53 for
      12 mo later and 24 mo later, respectively. Thus, although there was no
      statistically significant increase, it was confirmed that saliva secretion tended
      to increase. A VAS method was employed to study the intensities of subjective
      symptoms of oral dryness and eating difficulty. Almost every case indicated some
      improvement of subjective oral dryness on the VAS early in the administration,
      i.e., one month after. We also studied the effects of the administration of
      nizatidine on nutritional condition, hepatic functional reserve, and long-term
      prognosis of PBC. No significant improvements in cholinesterase (ChE) level,
      albumin (Alb) level, or Child-Pugh score were found during the period of
      observation from the beginning to the end of administration of nizatidine, nor in
      comparison with the non-administration group. A comparative analysis between
      before administration and 24 mo later yielded P values of 0.41 for Alb, 0.56 for
      ChE, and 0.59 for the Child-Pugh scores. CONCLUSION: It was confirmed that
      administering nizatidine to cases of PBC with dry mouth increased the secretion
      of saliva and improved the symptoms.

PMID- 23556040
TI  - Association between low molecular polypeptide 7 single nucleotide polymorphism
      and response to therapy in hepatitis C virus infection.
AB  - AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7)
      gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C
      virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide
      substitution from A to C was amplified in 104 chronic HCV patients of genotype 4.
      The amplicons were digested with restriction endonuclease BsmI and the produced
      restriction fragment length polymorphism was analyzed. Patients received IFN +
      regional blood volume therapy for 48 wk and the frequency of this single
      nucleotide polymorphism (SNP) was statistically correlated with treatment
      response. The exclusion criteria for these patients were stated by the national
      health program for treating viral hepatitis. Main exclusion criteria included co
      infection with hepatitis B virus or schistosomiasis, thyroid dysfunction,
      uncontrolled diabetes mellitus, history of long term drug or alcohol intake and
      autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus
      several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and
      alanine aminotransferase levels, liver activity, fibrosis score and viral load
      with response to therapy. RESULTS: The data presented in this study clearly
      demonstrated statistically significant differences between sustained virological
      response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at
      least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV
      RNA levels in the patient's sera never become undetectable for 6 mo during or
      after treatment). Variables were described as odds ratio with 95%CI. The data
      were considered significant if P values were <= 0.05; highly significant if P <
      0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of
      patients carrying LMP-7 C/C allele were associated with SVR, while the other two
      genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3%
      respectively, showing that genotype CC was strongly associated with response to
      interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters
      recorded in SVR and NR patients included higher values of mean age (P = 0.004),
      alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025),
      viral load (P = 0.025), higher fibrosis and histological activity index indices
      among NR vs SVR patients. Also, the multivariate statistical analysis of the
      different factors of fibrosis score, liver activity grade, genotypes and alleles
      of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study
      showed that HCV patients with A allele had a very highly significant association
      with the NRs, high fibrosis and higher liver activity, while the C allele had a
      very highly significant association with the responders, low fibrosis and lower
      liver activity (95%CI: 3.5800-13.2519, P = 0.0001). CONCLUSION: LMP-7 SNP is a
      candidate gene that should be considered when designing a mathematical model for
      predicting response to therapy and disease progression in HCV patients.

PMID- 23556041
TI  - Low incidence of spontaneous bacterial peritonitis in asymptomatic cirrhotic
      outpatients.
AB  - AIM: To compare the incidence of spontaneous bacterial peritonitis in cirrhotic
      outpatients and inpatients undergoing therapeutic paracentesis METHODS: From
      January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent
      2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure
      in 355 and as inpatient procedure in 686 cases respectively. The following
      parameters were compared prospectively between outpatients and inpatients:
      spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of
      cirrhosis, symptoms, score and grade according to Child-Pugh classification,
      cirrhosis complications, antibiotics treatment, serum creatinine, platelet count
      and ascitic protein concentration. RESULTS: SBP was observed in 91 patients. In
      the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7%
      (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P <
      0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs
      1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients
      undergoing outpatient AP were significantly different from those undergoing
      inpatient AP; they were older (61.1 +/- 11.1 years vs 59.4 +/- 11.7 years; P =
      0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001),
      Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C
      (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was
      higher (161 +/- 93 Giga/L vs 143 +/- 89 Giga/L; P = 0.003), serum total bilirubin
      concentration was lower (38.2 +/- 60.7 MUmol/L vs 96.3 +/- 143.3 MUmol/L; P <
      0.0001), and ascitic protein concentration higher (17.9 +/- 10.7 g/L vs 14.5 +/-
      10.9 g/L; P < 0.001) than in inpatients. CONCLUSION: In asymptomatic cirrhotic
      outpatients, the incidence of spontaneous bacterial peritonitis is low thus
      exploratory paracentesis could be avoided in these patients without significant
      risk.

PMID- 23556042
TI  - Silymarin in non alcoholic fatty liver disease.
AB  - AIM: This study was undertaken to evaluate the hepatic effects of silybum
      marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients
      affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were
      assayed after 3 mo of a restricted diet and before silymarin treatment (twice a
      day orally). The brightness of liver echography texture (hepatorenal ratio
      brightness) was also defined at same time. These evaluations were repeated after
      6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory
      data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato
      test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma
      glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the
      AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index
      of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained
      results indicate that silymarin appears to be effective to reduce the
      biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some
      parameters indicative of early stage of atherosclerosis were also lowered.

PMID- 23556043
TI  - Percutaneous trans-hepatic bilateral biliary stenting in Bismuth IV malignant
      obstruction.
AB  - AIM: To investigate the clinical efficiency of percutaneous trans-hepatic
      bilateral biliary metallic stenting for the management of Bismuth IV malignant
      obstructive disease. METHODS: Our hospital's database was searched for all
      patients suffering from the inoperable malignant biliary obstruction Bismuth IV,
      and treated with percutaneous bilateral trans-hepatic placement of self
      expandable nitinol stents. The indication for percutaneous stenting was an
      inoperable, malignant, symptomatic, biliary obstruction. An un-correctable
      coagulation disorder was the only absolute contra-indication for treatment.
      Bismuth grading was performed using magnetic resonance cholangiopancreatography.
      Computed tomography evaluation of the lesion and the dilatation status of the
      biliary tree was always performed prior to the procedure. All procedures were
      performed under conscious sedation. A single trans-hepatic track technique was
      preferred (T-configuration stenting) and a second, contra-lateral trans-hepatic
      track (Y-configuration stenting) was used only in cases of inability to access
      the contra-lateral lobe using a single track technique. The study's primary
      endpoints were clinical success, defined as a decrease in bilirubin levels within
      10 d and patient survival rates. Secondary endpoints included peri-procedural
      complications, primary and secondary patency rates. RESULTS: A total of 35
      patients (18 female, 51.4%) with a mean age 69 +/- 13 years (range 33-88) were
      included in the study. The procedures were performed between March 2000 and June
      2008 and mean time follow-up was 13.5 +/- 22.0 mo (range 0-96). The underlying
      malignant disease was cholangiocarcinoma (n = 10), hepatocellular carcinoma (n =
      9), pancreatic carcinoma (n = 5), gastric cancer (n = 2), bile duct tumor (n =
      2), colorectal cancer (n = 2), gallbladder carcinoma (n = 2), lung cancer (n =
      1), breast cancer (n = 1) or non-Hodgkin lymphoma (n = 1). In all cases, various
      self-expandable bare metal stents with diameters ranging from 7 to 10 mm were
      used. Stents were placed in Y-configuration in 24/35 cases (68.6%) using two
      stents in 12/24 patients and three stents in 12/24 cases (50%). A T-configuration
      stent placement was performed in 11/35 patients (31.4%), using two stents in 4/11
      cases (36.4%) and three stents in 7/11 cases (63.6%). Follow-up was available in
      all patients (35/35). Patient survival ranged from 0 to 1763 d and the mean
      survival time was 168 d. Clinical success rate was 77.1% (27/35 cases), and peri
      procedural mortality rate was 5.7% (2/35 patients). Biliary re-obstruction due to
      stent occlusion occurred in 25.7% of the cases (9/35 patients), while in 7/11
      (63.6%) one additional percutaneous re-intervention due to stent occlusion
      resulting in clinical relapse of symptomatology was successfully performed. In
      the remaining 4/11 patients (36.4%) more than 1 additional reintervention was
      performed. The median decrease of total serum bilirubin was 60.5% and occurred in
      81.8% of the cases (27/33 patients). The median primary and secondary patency was
      105 (range 0-719) and 181 d (range 5-1763), respectively. According to the Kaplan
      Meyer survival analysis, the estimated survival rate was 73.5%, 47.1% and 26.1%
      at 1, 6 and 12 mo respectively, while the 8-year survival rate was 4.9%. Major
      and minor complication rates were 5.7% (2/35 patients) and 17.1% (6/35 patients),
      respectively. CONCLUSION: Percutaneous bilateral biliary stenting is a safe and
      clinically effective palliative approach in patients suffering from Bismuth IV
      malignant obstruction.

PMID- 23556044
TI  - Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic
      patients: A systematic review.
AB  - AIM: To identify severe adverse events (SAEs) leading to treatment
      discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)
      infected cirrhotic patients. METHODS: We identified all the articles published
      prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE,
      Cochrane and Medscape databases that presented these data in cirrhotic patients.
      These studies evaluated the rate of SAEs leading to discontinuation of standard
      care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 MUg/wk) or PegIFN
      alpha 2b (1 or 1.5 MUg/kg per week) and ribavirin (800-1200 mg/d). Patients with
      genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3
      were treated for 24 wk. RESULTS: We included 17 papers in this review, comprising
      of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the
      patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia
      (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%)
      and severe anemia (11.2%). The proportion of patients who needed to discontinue
      their therapy due to SAEs was significantly higher in patients with Child-Pugh
      class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A
      similar discontinuation rate was found in cirrhotic patients treated with PegIFN
      alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin:
      14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in
      cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in
      patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI:
      17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001). CONCLUSION: Fourteen point
      five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed
      early discontinuation of therapy due to SAEs, the most common cause being
      hematological disorders.

PMID- 23556045
TI  - Liver transplantation in Wilson's disease: Single center experience from Saudi
      Arabia.
AB  - AIM: To determine liver transplantation outcomes in Wilson's disease (WD)
      patients, focusing on neurological manifestations. METHODS: This retrospective
      study assessed data from 16 WD patients (nine males, 56%) who had liver
      transplants between 1991 and 2007. Survival, graft function, and neurological
      complications were assessed during a follow-up period of up to 15 years. In
      addition, each patient's medical record was reviewed in detail to find the type
      of Wilson's disease (hepatic or hepatic plus neurological WD), indication for
      liver transplantation, use of chelating agents prior to transplantation,
      immediate and long term complications following transplantation, the donor
      details, and the pathology of explanted liver. RESULTS: End-stage liver disease
      was the indication for transplantation in all 16 WD patients. Four patients
      displayed WD-related neurological symptoms in addition to liver disease. Living
      related liver transplantation was done in three cases. One patient died on
      postoperative day 6 due to primary graft non-function. One-year post liver
      transplant survival was 94%. Neurological manifestations of all four patients
      disappeared during their follow-up. Four patients developed acute cellular
      rejection, but all responded to treatment. One patient developed chronic
      ductopenic rejection after 15 years post-transplantation and their graft failed;
      this patient is currently waiting for re-transplantation. Fourteen patients (88%)
      are still living. The long-term average survival is currently 10.5 years, with a
      current median survival of 8 years. Long-term graft survival is currently 81%.
      CONCLUSION: Short- and long-term survival in WD patient liver transplantation was
      excellent, and neurological and psychological WD manifestations disappeared
      during long-term follow-up.

PMID- 23556046
TI  - Mastabol induced acute cholestasis: A case report.
AB  - A 26-year-old male presented with three weeks of jaundice after the self
      initiation of the injectable anabolic steroid, Mastabol [Dromastanolone Di
      Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3-one propionate)]. He
      reported dark urine, light stools, and pruritus. He denied abdominal pain,
      intravenous drug use, intranasal cocaine, blood transfusions, newly placed
      tattoos, or sexually transmitted diseases. He used alcohol sparingly. Physical
      exam revealed jaundice with deep scleral icterus. The liver was palpable 2 cm
      below the right costal margin with no ascites. The peak bilirubin was 23.6 mg/dL,
      alkaline phosphatase was 441 units/L, and aspartate aminotransferase/alanine
      aminotransferase were 70 units/L and 117 units/L respectively. A working
      diagnosis of acute intrahepatic cholestasis was made. Liver biopsy revealed a
      centrilobular insult with neutrophilic infiltrates and Ito cell hyperplasia
      consistent with acute drug induced cholestasis. The patient's clinical symptoms
      resolved and his liver enzymes, bilirubin, and alkaline phosphatase normalized.
      Anabolic steroids with 17 alpha carbon substitutions have been associated with a
      bland variety of cholestatic injury with little hepatocellular injury.
      Cholestasis, under these circumstances, may be secondary to the binding of drugs
      to canalicular membrane transporters, accumulation of toxic bile acids from
      canalicular pump failure, or genetic defects in canalicular transport proteins.
      Mastabol is an injectable, 17 beta hydroxyl compound with no alpha alkyl groups
      at the 17 carbon position. As such, it has been reported to have little potential
      toxic effects on the liver. This is the first known reported case of Mastabol
      induced cholestatic liver injury. It highlights the need for physicians to
      consider such widely available substances when faced with hepatic injury of
      unclear etiology.

PMID- 23556047
TI  - Portal hypertensive biliopathy: A single center experience and literature review.
AB  - Portal hypertensive biliopathy (PHB) is characterized by anatomical and
      functional abnormalities of the intrahepatic, extrahepatic and pancreatic ducts,
      in patients with portal hypertension associated to extrahepatic portal vein
      obstruction and less frequently to cirrhosis. These morphological changes,
      consisting in dilatation and stenosis of the biliary tree, are due to extensive
      venous collaterals occurring in an attempt to decompress the portal venous
      blockage. It is usually asymptomatic until it progresses to more advanced stages
      with cholestasis, jaundice, biliary sludge, gallstones, cholangitis and finally
      biliary cirrhosis. Imaging modalities of the biliary tree such as Doppler
      ultrasound, computed tomography, magnetic resonance cholangiopancreatography and
      endoscopic retrograde cholangiopancreatography are essential to establish the
      diagnosis and the need of therapeutical interventions. Once the diagnosis is
      established, treatment with ursodesoxycholic acid seems to be beneficial.
      Decompression of the biliary tree to dilate, remove stones or implant biliary
      prosthesis by endoscopic or surgical procedures (hepato-yeyunostomy) usually
      resolves the cholestatic picture and prevents septic complications. The ideal
      treatment is the decompression of the portal system, with transjugular
      intrahepatic porto-systemic shunt or a surgical porto-systemic shunt.
      Unfortunately, few patients will be candidates for these procedures due to the
      extension of the thrombotic process. The purpose of this paper is to report the
      first 3 cases of PHB seen in a Colombian center and to review the literature.

PMID- 23556048
TI  - Liver transplantation for recurrent hepatic adenoma.
AB  - Hepatic adenoma (HA) is a rare indication for liver transplantation (LTx). So far
      20 cases of LTx for HA are reported in PubMed. In rare cases HA presents as
      multiple hepatic adenomas or recurrent adenoma after initial liver resection and
      in such cases LTx is the only potential cure and prevents the risk of bleeding or
      cancer transformation into hepatocellular carcinoma. We report the case of a 56
      years old lady who underwent a left hepatectomy for giant adenoma in 2005 and
      resection of segment V-VI for recurrence of liver adenoma in 2007. She developed
      a second recurrence of HA with 3 new lesions in the right liver in 2008. The
      patient underwent LTx. After 3 years the patient is alive with no evidence of
      disease. LTx is indicated in patients with HA in which resection is not
      technically feasible.

PMID- 23556049
TI  - Extrahepatic aneurysm of the portal venous system and portal hypertension.
AB  - Portal venous aneurysm (PVA) is a rare condition characterized by dilatation of
      the portal venous system. PVA manifestation of symptoms is varied and depends on
      the aneurysm size, location and related-complications, such as thrombosis. While
      the majority of reported cases of PVA are attributed to portal hypertension, very
      little is known about the condition's pathophysiology and clinical management
      remains a challenge. Here, we describe a 67-year-old woman who presented with
      complaint of dyspepsia and without a significant medical history, for whom PVA
      was incidentally diagnosed. The initial upper abdominal ultrasound revealed
      marked dilatation of the main portal vein, and subsequent contrast-enhanced
      computed tomography with angiography revealed a large aneurysm arising from the
      extrahepatic troncus portion of the portal vein, as well as gastroesophageal
      varices. A conservative approach using beta-blocker therapy was chosen. The
      patient was followed-up for 60 mo, during which time the asymptomatic status was
      unaltered and the PVA remained stable.

PMID- 23556050
TI  - Case of acute hepatitis E with concomitant signs of autoimmunity.
AB  - Sporadic cases of acute viral hepatitis E have been described in developed
      countries, despite the more common occurrence in endemic areas and developing
      countries. We present the case of a 58 years old Portuguese female, with no
      epidemiological relevant factors, admitted with acute hepatitis with positive
      anti-nuclear antibodies, anti-smooth muscle antibody and high serum gamma
      globulin (> 1.5 fold increase). Serologies for hepatitis A virus, hepatitis B
      virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, hereditary sensory
      neuropathy and varicella zoster virus were negative. Liver biopsy histology
      revealed changes compatible with autoimmune hepatitis. Prednisolone and
      azathioprine was started. She tested positive for immunoglobulin M anti hepatitis
      E virus (HEV) with detectable viremia by reverse transcription polymerase chain
      reaction (RT-PCR) technique. HEV-RNA was confirmed through RT-PCR in a liver
      specimen, establishing the diagnosis of acute hepatitis E. Immunosuppression was
      stopped. She clinically improved, with resolution of laboratory abnormalities.
      Therefore, we confirmed acute hepatitis E as the diagnosis. We review the
      literature to elucidate about HEV infection and its autoimmune effects.

PMID- 23556051
TI  - Genetically confirmed Wilson disease in a 9-month old boy with elevations of
      aminotransferases.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper transport caused
      by alteration of the adenosine triphosphatase 7B gene. It is rare to diagnose WD
      below the age of three years. Molecular genetic testing is one of the most
      important diagnostic methods and may confirm the diagnosis in equivocal cases. We
      report a case of a 9-mo old boy with WD who presented as chronic hepatitis.
      Genetic analysis showed compound heterozygotes of p.G1186S and c.4006delA.

PMID- 23556052
TI  - Era of universal testing of microsatellite instability in colorectal cancer.
AB  - Colorectal cancer (CRC) incidence and mortality are constantly decreasing, but
      CRC still remains the third most prevalent cancer and the third most common cause
      of cancer death in both males and females in the United States. Recent rapid
      declines in CRC incidence rates have largely been attributed to increases in
      screening that can detect and remove precancerous polyps, and the decrease in
      death rates for CRC largely reflects improvements in early detection, treatment
      and the understanding of molecular/genetic basis of CRC. One of the important
      molecular/genetic findings is the presence of microsatellite instability (MSI) in
      CRCs. Many studies have shown the importance of MSI testing in diagnosing Lynch
      syndrome and predicting prognosis and response to chemotherapeutic agents in
      CRCs. Increased emphasis has been placed on the importance of MSI testing for all
      newly diagnosed individuals with CRCs. Both immunohistochemical staining (IHC)
      and polymerase chain reaction (PCR)-based MSI testing show high sensitivity and
      specificity in detecting MSI. The current clinical guidelines and histopathology
      features are indicative of, but not reliable in diagnosing Lynch syndrome and
      CRCs with MSI. Currently, there are evidences that universal testing for MSI
      starting with either IHC or PCR-based MSI testing is cost effective, sensitive,
      specific and is getting widely accepted.

PMID- 23556053
TI  - Current developments, problems and solutions in the non-surgical treatment of
      pancreatic cancer.
AB  - Pancreatic cancer is a common malignant neoplasm of the pancreas with an
      increasing incidence, a low early diagnostic rate and a fairly poor prognosis. To
      date, the only curative therapy for pancreatic cancer is surgical resection, but
      only about 20% patients have this option at the time of diagnosis and the mean 5
      year survival rate after resection is only 10%-25%. Therefore, developing new
      treatments to improve the survival rate has practical significance for patients
      with this disease. This review deals with a current unmet need in medical
      oncology: the improvement of the treatment outcome of patients with pancreatic
      cancer. We summarize and discuss the latest systemic chemotherapy treatments
      (including adjuvant, neoadjuvant and targeted agents), radiotherapy,
      interventional therapy and immunotherapy. Besides discussing the current
      developments, we outline some of the main problems, solutions and prospects in
      this field.

PMID- 23556054
TI  - Gallbladder carcinoma in a pregnant patient with Crohn's disease complicated with
      gallbladder involvement.
AB  - Primary gallbladder (GB) carcinoma and Crohn's disease (CD) of the GB are
      individually rare. We present a case of a pregnant woman with CD found to have GB
      involvement and primary GB carcinoma. A 34-year-old female at 6 wk gestation with
      a 21 year history of CD of uncertain extent presented with 3 mo of diarrhea,
      urgency and abdominal pain. During work-up, she was found to have elevated
      transaminases and an abnormal alkaline phosphatase. Imaging revealed two
      gallbladder polyps both greater than 1 cm in size. Resection and histological
      evaluation was consistent with Crohn's involvement of the GB, poorly
      differentiated adenocarcinoma of the GB with invasion through the muscularis
      propria and matted lymph nodes in the porta hepatis positive for metastatic
      carcinoma (stage pT2N1). Six cases of CD involving the GB, two cases of primary
      GB carcinoma in CD, and ten cases of cholangiocarcinoma in pregnancy have been
      published. This is the only case that describes all three factors. Common
      features in CD of the GB include acute cholecystitis, ileal involvement, and
      presence independent of active intestinal disease. Common features in CD patients
      with GB malignancy include younger age of detection, a long history of CD,
      extensive colonic and ileal involvement of disease, the absence of
      cholelithiasis, and pre-existing gallbladder disease (primary sclerosing
      cholangitis and gallbladder polyps). Pregnancy is specific to this case. The role
      of CD in the development of GB malignancy is not well understood nor is the
      contribution of pregnancy to the spread of disease. Chronic inflammation and
      immunosuppression compounded by hormonal influence is implicated.

PMID- 23556055
TI  - Diffuse intestinal ganglioneuromatosis an uncommon manifestation of Cowden
      syndrome.
AB  - Diffuse intestinal ganglioneuromatosis is a hamartomatous polyposis characterized
      by a disseminated, intramural or transmural proliferation of neural elements
      involving the enteric plexuses. It has been associated with MEN II,
      neurofibromatosis type 1 and hamartomatous polyposis associated with phosphatase
      and tensin homolog mutation. We report the case of a female patient with a
      history of a breast and endometrial tumor who presented in a colonoscopy
      performed for rectal bleeding diffuse ganglioneuromatosis, which oriented the
      search for other characteristic findings of Cowden syndrome given the personal
      history of the patient. The presence of an esophagogastric polyposis was also
      noted. Cowden syndrome is characterized by skin lesions, but it is rarely
      diagnosed by these lesions, because they are usually overlooked. Intestinal
      polyposis is not a major diagnostic criterion but it is very useful for early
      diagnosis. The combination of colonic polyposis and glucogenic acanthosis should
      orient the diagnosis to Cowden syndrome.

PMID- 23556056
TI  - Complete remission of advanced hepatocellular carcinoma by sorafenib: A case
      report.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignant disease
      worldwide, and curative treatment remains difficult because the majority of cases
      are diagnosed in the advanced stage. Sorafenib is the only known effective
      systemic treatment, but patients rarely achieve complete remission (CR). A 66
      year-old man with a history of alcoholic liver cirrhosis with a diagnosis of
      advanced HCC, was initially treated with transarterial chemoembolization on four
      occasions. However, the disease progressed with portal vein thrombosis.
      Therefore, sorafenib was started, and 4 mo later, the patient achieved CR. The
      treatment was continued for 12 mo, and CR was maintained up to 4 mo after
      sorafenib discontinuation.

PMID- 23556057
TI  - Is there a role for arterial reconstruction in surgery for pancreatic cancer?
AB  - Surgery remains the only potentially curative treatment for patients with
      pancreatic cancer. Locally advanced pancreatic cancer with vascular involvement
      remains a surgical challenge because high perioperative risk and the uncertainty
      of a survival benefit. Whilst portal vein resection has started to gather
      momentum because the perioperative morbidity and long term survival is comparable
      to standard pancreatectomy, there isn't yet a consensus on arterial resections.
      There have been various reports and case series of arterial resections in
      pancreatic cancer, with mixed survival results. Mollberg et al have appraised the
      heterogeneous published literature available on arterial resection in pancreatic
      cancer in an attempt to compare this to standard pancreatectomy. In this article,
      we discuss the results of this systematic review and meta-analysis, and the
      limitations associated with analysing results from heterogenous data. We have
      outlined the important features in surgery for pancreatic cancer and specifically
      to arterial resections, and compared arterial resections to the published
      literature on venous resections.

PMID- 23556058
TI  - Hepatic histopathology and postoperative outcome after preoperative chemotherapy
      for Chinese patients with colorectal liver metastases.
AB  - AIM: To assess the effects of preoperative treatment on the hepatic histology of
      non-tumoral liver and the postoperative outcome. METHODS: One hundred and six
      patients underwent hepatic resection for colorectal metastases between 1999 and
      2009. The surgical specimens were reviewed with established criteria for
      diagnosis and grading of pathological hepatic injury. The impact of preoperative
      therapy on liver injury and postoperative outcome was analyzed. RESULTS: Fifty
      three patients (50%) received surgery alone, whereas 42 patients (39.6%) received
      neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic
      artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%)
      and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients
      (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%)
      had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal
      dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the
      perioperative complication rate was not significantly different between the
      oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated
      with more steatosis, sinusoidal dilation and steatohepatitis than the surgery
      group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and
      mortality (9.1% vs 0% P = 0.02). CONCLUSION: Preoperative oxaliplatin was
      associated with sinusoidal dilation compared with surgery alone. However, the
      preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI
      can cause pathological changes and tends to increase perioperative morbidity and
      mortality.

PMID- 23556059
TI  - Clostridium difficile enteritis: A report of two cases and systematic literature
      review.
AB  - Clostridium difficile (C. difficile) is the most common cause of healthcare
      associated infectious diarrhea. In the last decade, the incidence of C. difficile
      infection has increased dramatically. The virulence of C. difficile has also
      increased recently with toxigenic strains developing. C. difficile is generally a
      disease of the colon and presents with abdominal pain and diarrhea due to
      colitis. However, C. difficile enteritis has been reported rarely. The initial
      reports suggested mortality rates as high as 66%. The incidence of C. difficile
      enteritis appears to be increasing in parallel to the increase in colonic
      infections. We present two cases of patients who had otherwise uneventful
      abdominal surgery but subsequently developed C. difficile enteritis. Our
      literature review demonstrates 81 prior cases of C. difficile enteritis described
      in case reports. The mortality of the disease remains high at approximately 25%.
      Early recognition and intervention may reduce the high mortality associated with
      this disease process.

PMID- 23556060
TI  - Recurrent intestinal volvulus in midgut malrotation causing acute bowel
      obstruction: A case report.
AB  - Intestinal malrotation occurs when there is a disruption in the normal
      embryological development of the bowel. The majority of patients present with
      clinical features in childhood, though rarely a first presentation can take place
      in adulthood. Recurrent bowel obstruction in patients with previous abdominal
      operation for midgut malrotation is mostly due to adhesions but very few reported
      cases have been due to recurrent volvulus. We present the case of a 22-year-old
      gentleman who had laparotomy in childhood for small bowel volvulus and then
      presented with acute bowel obstruction. Preoperative computerised tomography scan
      showed small bowel obstruction and features in keeping with midgut malrotation.
      Emergency laparotomy findings confirmed midgut malrotation with absent appendix,
      abnormal location of caecum, ascending colon and small bowel. In addition, there
      were small bowel volvulus and a segment of terminal ileal stricture. Limited
      right hemicolectomy was performed with excellent postoperative recovery. This
      case is presented to illustrate a rare occurrence and raise an awareness of the
      possibility of dreadful recurrent volvulus even several years following an
      initial Ladd's procedure for midgut malrotation. Therefore, one will need to
      exercise a high index of suspicion and this becomes very crucial in order to
      ensure prompt surgical intervention and thereby preventing an attendant bowel
      ischaemia with its associated high fatality.

PMID- 23556061
TI  - Perforated duodenal diverticulum, a rare complication of a common pathology: A
      seven-patient case series.
AB  - Duodenal diverticula (DD) are frequently encountered and are usually
      asymptomatic, with an incidence at autopsy of 22%. Perforation of DD is a rare
      complication (around 160 cases reported) with potentially dramatic consequences.
      However, little evidence regarding its treatment is available in the literature.
      The aim of this study was to review our experience of perforated DD, with a focus
      on surgical management. Between January 2001 and June 2011, all perforated DD
      were retrospectively reviewed at a single centre. Seven cases (5 women and 2 men;
      median age: 72.4 years old, rang: 48-91 years) were found. The median American
      Society of Anesthesiologists' score in this population was 3 (range: 3-4). The
      perforation was located in the second portion of duodenum (D2) in six patients
      and in the third portion (D3) in one patient. Six of these patients were treated
      surgically: five patients underwent DD resection with direct closure and one was
      treated by surgical drainage and laparostomy. One patient was treated
      conservatively. One patient died and one patient presented a leak that was
      successfully treated conservatively. The median hospital stay was 21.1 d (range:
      15-30 d). Perforated DD is an uncommon presentation of a common pathology.
      Diverticular excision with direct closure seems to offer the best chance of
      survival and was associated with a low morbidity, even in fragile patients.

PMID- 23556062
TI  - Liver blood supply after a modified Appleby procedure in classical and aberrant
      arterial anatomy.
AB  - Reported here are two cases of a modified Appleby operation for borderline
      resectable ductal adenocarcinoma of the pancreatic body, in one of which a R0
      distal resection was attended to by excision, not only of the celiac axis, but
      also of the common and left hepatic arteries in the presence of arterial anatomic
      variation Michels, type VIIIb. The possibility and avenues of the maintenance of
      the blood supply to the left hepatic lobe after surgical aggression of this kind
      are demonstrated employing computed tomography (CT) and 3-D CT angiography.
      Furthermore, both cases highlight all important worrisome aspects of pancreatic
      cancer resectability prediction.

PMID- 23556063
TI  - Mesenteric paraganglioma: Report of a case.
AB  - We report a rare case of paraganglioma that developed in the mesentery of
      terminal ileum. A 78-year-old woman complained of right-sided abdominal pain.
      Abdominal computed tomography revealed a solid heterogeneously enhanced mass in
      the right lower abdomen. The tumor was laparoscopically excised. The mesenteric
      tumor was well circumscribed, ovoid, and encapsulated and measured 3 cm * 1.5 cm
      * 1.5 cm. Histological examination showed a cellular neoplasm comprised of nests
      and groups of tumor cells separated by fibrovascular connective tissue, giving a
      characteristic nested Zellballen pattern. Immunohistochemically, the tumor cells
      were positive for chromogranin, synaptophysin, CD56, and vimentin and negative
      for cytokeratins, SMA, CD34, CD117/c-kit and S100. On the basis of histologic and
      immunohistochemical features, a diagnosis of mesenteric paraganglioma was made.
      The operative and postoperative courses were unremarkable, and the patient was
      discharged on postoperative day 7. She was doing well 1 year after the surgery
      with no signs of recurrence. Extra-adrenal paragangliomas most commonly develop
      adjacent to the aorta, particularly the area corresponding to the organ of
      Zuckerkandl. Mesenteric paraganglioma, as in our case, is extremely rare; only 11
      cases have been reported in the literature. We herein discuss the clinical
      findings of these cases.

PMID- 23556064
TI  - Pancreatic insulinoma combined with glucagon positive cell: A case report.
AB  - We present a 70-year-old man who was referred for surgery with uncontrollable
      hypoglycemia. Ultrasonography and abdominal contrast computed tomography revealed
      a hypervascular tumor of 1 cm in diameter in the pancreatic tail. With a
      diagnosis of insulinoma, we performed a distal pancreatectomy. The patient showed
      a good postoperative course without any complications. The patient's early
      morning fasting hypoglycemia disappeared. The respective levels of C-peptide and
      insulin dropped from 14.9 ng/mL and 4860 MUIU/mL preoperatively to 5.3 ng/mL and
      553 MUIU/mL after surgery. A histopathological examination demonstrated that the
      tumor was a pancreatic neuroendocrine tumor, grade 1. Immunostaining was negative
      for insulin and positive for CD56, chromogranin A, synaptophysin and glucagon.
      These findings suggested that the tumor was clinically an insulinoma but
      histopathologically a glucagonoma. Among all insulinoma cases reported between
      1985 and 2010, only 5 cases were associated with independent glucagonoma. In this
      report, we characterize and discuss this rare type of insulinoma by describing
      the case we experienced in detail.

PMID- 23556066
TI  - Editorial.

PMID- 23556065
TI  - Nightmares that mislead to diagnosis of reactivation of PTSD.
AB  - BACKGROUND: Sleep disturbance is a common characteristic of patients with post
      traumatic stress disorder (PTSD). Besides the clinical descriptions of nightmares
      and insomnia, periodic limb movements (PLMs) are reported to co-occur in PTSD.
      Although the causal relationship between sleep disturbance and PTSD is not fully
      understood, sleep disturbance is an independent risk factor for the development
      and reactivation of PTSD. In contrast, the link between PTSD and REM sleep
      behaviour disorder (RBD) is less clear. METHOD: A case report is presented to
      illustrate differential diagnosis and time course of sleep disturbance in the
      context of PTSD. RESULT: A 63-year-old man who had been successfully treated for
      PTSD but who suffered the re-occurrence of disturbed sleep due to RBD and PLM,
      which was misdiagnosed as reactivation of PTSD. CONCLUSIONS: RBD can mimic PTSD
      related nightmares. Accurate diagnosis of sleep disturbance in PTSD is relevant
      for treatment and prognostic evaluation.

PMID- 23556068
TI  - First-line treatment of chronic myeloid leukaemia.
AB  - Since the introduction of imatinib just over a decade ago, there has been a
      dramatic change in the treatment and prognosis of early chronic phase chronic
      myeloid Leukaemia (CML). This review article focuses on recent advances,
      culminating in the approval of nilotinib by the US Food and Drug Administration
      for the treatment of adult patients with newly diagnosed CML in the chronic
      phase.

PMID- 23556067
TI  - Allogeneic transplant for chronic myeloid leukemia in 2010.
AB  - Tyrosine kinase inhibitor (TKI) therapy has revolutionized the therapy of chronic
      myeloid Leukemia (CML). Thus, while in the near past allogeneic transplantation
      was the curative option for CML, imatinib, nilotinib, and dasatinib have pushed
      transplantation to the role of salvage therapy in CML. Still, TKI therapy still
      fails some patients, and so the clinical challenge is to integrate
      transplantation in a safe and sane manner. This manuscript reviews the data on
      the variables that have an influence on outcome following transplantation, and
      discusses the variables to consider in determining who and when patients should
      receive transplantation.

PMID- 23556069
TI  - Novel therapies for Hodgkin Lymphoma.
AB  - In recent years, improved understanding of the biology of Hodgkin Lymphoma (HL)
      has uncovered many potential targets for the treatment of this disease.
      Clarification of the B-ceLL origin of the Hodgkin Reed Sternberg (HRS) cell and
      of the complex interactions between the HRS cell and the HL microenvironment have
      provided new insights into the pathophysiology of HL and identified extracellular
      and intracellular molecules which are essential for HRS survival. New agents
      directed at these molecules are now in early phase clinical trials.

PMID- 23556070
TI  - Editorial.

PMID- 23556071
TI  - Long-Term Results of Fludarabine/Melphalan as a Reduced-Intensity Conditioning
      Regimen in Mantle Cell Lymphoma: The GELTAMO Experience.
AB  - BACKGROUND: We herein report the long-term results of an allogeneic reduced
      intensity conditioning (allo-RIC) protocol used in 21 consecutive patients (16
      males, median age 56 years, 71% in complete remission) diagnosed with mantle cell
      lymphoma (MCL). METHODS: The allo-RIC consisted of fludarabine plus melphalan and
      peripheral blood hematopoietic stem cells (PBSCs) from human leukocyte antigen
      (HLA)-identical siblings were used in all cases. Median CD34+ infused cells was
      5.8 times 10(6)/kg. All patients engrafted promptly. RESULTS: Early toxicity
      included mild/moderate mucositis (43%), febrile neutropenia (33%) and bacterial
      infections (19%). With a median follow up of 48 months, four deaths were
      reported, all due to infections and/or graft-versus-host disease (GVHD), yielding
      a 3-year cumulative incidence of nonrelapse mortality of 19.5%. Grade III-IV
      acute GVHD occurred in 15% and chronic GVHD in 78%, being extensive in 39%. The 5
      year progression-free survival (PFS) and overall survival (OS) were both 80% (95%
      CI: 63-97%). Age was the only possible prognostic factor for OS, which was 43%
      for those aged more than 60 years and 100% for those younger (p < 0.001).
      CONCLUSIONS: Our data confirm that allo-RIC offers a low toxicity profile and a
      chance for prolonged long-term disease-free survival in MCL, particularly in
      younger patients.

PMID- 23556072
TI  - When the Brakes are Lost: LNK Dysfunction in Mice, Men, and Myeloproliferative
      Neoplasms.
AB  - Aberrant JAK-STAT signaling is a hallmark of myeloproliferative neoplasms (MPNs).
      These hyperproliferative disorders are classically associated with activating
      mutations in tyrosine kinases such as JAK2 and the thrombopoietin (TPO) receptor
      MPL. Activation of JAK-STAT signaling and responses to JAK2 inhibitors have been
      observed in MPN patients lacking JAK2 or MPL mutations, suggesting that other
      regulatory elements in the JAK-STAT pathway are altered. However, the molecular
      basis for this observation has been unclear. Recently, the role of inhibitory
      regulators of JAK-STAT signaling in MPN pathogenesis has been increasingly
      recognized. LNK is an adaptor protein that forms a negative feedback loop by
      binding to MPL and JAK2 and inhibiting downstream STAT activation. Murine models
      indicate that loss of LNK function can promote the development of a MPN
      phenotype. Several recent studies have identified novel LNK mutations in MPNs,
      thus validating this notion in humans. These findings represent a novel genetic
      paradigm of loss of negative feedback regulation of JAK-STAT activation in MPNs
      and have implications for the future development of targeted therapies in MPNs.

PMID- 23556074
TI  - The revolution of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are clonal disorders of the hematopoietic system
      with resultant cytopenias and shortened survival. Better recognition of MDS and
      an aging population, some of whom have been treated with chemotherapy and
      radiation therapy for other cancers, is largely responsible for the growing
      incidence of this malignancy, which is divided into lower- and higher-risk
      subtypes. Erythropoiesis-stimulating agents are the first-line treatment options
      for patients with lower-risk MDS and symptomatic anemia or for those requiring
      transfusion support. Lenalidomide has been successfully used for patients with
      the del(5q) chromosomal abnormality who are also transfusion dependent.
      Hypomethylating agents, such as azacitidine and decitabine, are indicated for
      patients with higher-risk disease, with azacitidine demonstrating a survival
      advantage. Hematopoietic stem cell transplantation (HSCT) is a curative
      therapeutic approach available to less than 5% of patients with MDS. Combination
      therapies and newer single agents targeting the important cellular pathways are
      being explored for treatment of MDS with promising results.

PMID- 23556076
TI  - Editorial.

PMID- 23556075
TI  - The emerging role of lenalidomide in the management of lymphoid malignancies.
AB  - Lenalidomide, a novel immunomodulatory drug (IMiD), is a promising therapeutic
      strategy for patients with relapsed/refractory chronic lymphocytic leukemia (CLL)
      and B-cell lymphomas. Biologically, the mechanisms responsible for lenalidomide
      activity are yet to be clearly defined. Based on preclinical models and early
      correlative studies conducted in parallel to clinical trials, lenalidomide has
      been found to enhance natural killer (NK)- and T-cell activity against tumor
      cells, alter the balance of pro- and anti-inflammatory cytokines in the tumor
      bed, inhibit angiogenesis, and, to a lesser degree, induce cell cycle arrest and
      apoptosis in cancer cells. Together, all of these biological effects appear to
      play a role in the activity observed in CLL or lymphoma patients treated with
      lenalidomide. Given the effect in NK- and T-cell function, lenalidomide is an
      alternative strategy to enhance the antitumor activity of monoclonal antibodies
      (mAbs). Clinical responses have been observed in patients with
      relapsed/refractory CLL, follicular lymphoma, small lymphocytic lymphoma, mantle
      cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) treated with
      lenalidomide single agent. The favorable toxicity profile and route of
      administration made the use of lenalidomide an attractive therapy for certain
      types of patients (i.e. elderly, chemotherapy unfit, etc.). The erratic but
      serious incidence of tumor lysis syndrome and/or tumor flare reactions provides
      challenges in the incorporation of lenalidomide in the management of previously
      untreated CLL or CLL/lymphoma patients with bulky adenopathy. Correlative studies
      and/or retrospective analysis of lenalidomide-treated patients had identified
      several biomarkers associated with clinical endpoints in CLL (i.e. changes in
      tumor necrosis factor alpha [TNF-alpha] or vascular endothelial growth factor
      [VEGF] levels) or DLBCL (non-GCB phenotype) patients, but need to be validated.
      Early studies evaluating the efficacy and toxicity of lenalidomide in combination
      with rituximab in previously untreated indolent lymphoma are promising and
      warrant further study. In addition, the evaluation of lenalidomide in the
      maintenance setting or in combination with other target-specific agents (i.e.
      proteasome inhibitors) in aggressive lymphomas is being addressed in ongoing
      clinical trials. In summary, lenalidomide is emerging as a biologically active
      and novel agent in the treatment of B-cell neoplasms. Future translational and
      clinical studies will further define the role of lenalidomide in the management
      of de novo or relapsed/refractory CLL or B-cell lymphomas and identify the subset
      of patients most likely to gain clinical benefit.

PMID- 23556073
TI  - JAK2 Allele Burden in the Myeloproliferative Neoplasms: Effects on Phenotype,
      Prognosis and Change with Treatment.
AB  - The field of Philadelphia-chromosome-negative chronic myeloproliferative
      neoplasms (MPNs) has recently witnessed tremendous advances in the basic
      knowledge of disease pathophysiology that followed the identification of
      mutations in JAK2 and MPL. These discoveries led to a revision of the criteria
      employed for diagnosis by the World Health Organization. The prognostic role of
      the JAK2V617F mutation and of its allelic burden has been the objective of
      intensive research using a variety of cellular and animal models as well as in
      large series of patients. While a definitive position cannot yet been taken on
      all of the issues, there is a consensus that the presence of higher V617F allele
      burden, that is on the basis of a stronger activation of intracellular signalling
      pathways, is associated with the clinical phenotype of polycythemia vera and with
      defined haematological and clinical markers indicative of a more aggressive
      phenotype. On the other hand, a low allele burden in myelofibrosis is associated
      with reduced survival. Finally, a significant reduction of JAK2 V617F allele
      burden has been demonstrated in patients treated with interferon, while the
      effects of novel JAK1 and JAK2 inhibitors have not yet been fully ascertained.

PMID- 23556077
TI  - Update on JAK2 Inhibitors in Myeloproliferative Neoplasm.
AB  - Since the discovery of mutant Janus Kinase 2 (JAK2), JAK2 V617F, in a major
      proportion of myeloproliferative neoplasm (MPN) patients, there has been a flurry
      of activity in the development of JAK2 inhibitors. Pan-JAK, predominantly JAK2
      and off-target JAK2 inhibitors have been developed in the short span of the past
      5 years. These compounds have since been tested to varying success in both in
      vitro and in vivo settings with several proceeding on to advanced clinical
      trials. Although it was hoped that these inhibitors would be the silver bullet in
      the manner than imatinib was to chronic myeloid leukemia, it is becoming apparent
      that this is not the case for various reasons, chief of which is that a
      significant reduction of the underlying pathogenic clone is not achieved. In
      fact, the very notion that the target of JAK2 inhibitors (be it pan-JAK or JAK2
      specific) is the mutant JAK2 V617F is being challenged with findings from several
      clinical trials showing a poor correlation between the reduction in JAK2 V617F
      mutant allele burden and clinical response. In view of this, it is not surprising
      that several groups are now investigating combinations of JAK2 inhibitors and
      other agents in MPN. Although much knowledge has been added in this short span of
      time, it is apparent that our understanding of the role of JAK2 inhibitors in the
      treatment scheme of MPN is only beginning.

PMID- 23556078
TI  - Salvage therapy for relapsed or refractory acute myeloid leukemia.
AB  - There are a significant number of patients diagnosed with acute leukemia who
      either fail to achieve remission or who relapse thereafter. Challenges in
      treating this patient population include accurately assessing prognosis of
      disease and whether remission can be achieved; assessing the ability of patients
      to tolerate aggressive salvage therapies; choosing a salvage therapy that is most
      likely to succeed; and identifying suitable patients for hematopoietic stem cell
      transplantation. Despite the development of a variety of new investigational
      therapies, relapsed or refractory acute myeloid Leukemia remains a difficult
      clinical problem. Clinicians will need to consider all currently available
      approaches, including cytotoxic chemotherapy, targeted agents, and allogeneic
      stem cell transplantation, to optimize outcomes.

PMID- 23556079
TI  - Rapid Identification of Therapeutic Targets in Hematologic Malignancies via
      Functional Genomics.
AB  - The clinical application of gene-targeted drugs has transformed cancer therapy.
      The hallmark example of this strategy is use of the ABL kinase inhibitor imatinib
      for treatment of patients with chronic myeloid leukemia (CML). This remarkable
      clinical success has also stimulated an expansive search for personalized gene
      targets in all patients to facilitate broad application of targeted therapy for
      cancer. However, achievement of this objective will require simultaneous work
      towards several complementary goals. The first step towards broad application of
      gene-targeted therapy must entail a rapid means to identify target oncogenes in
      individual patients. Next, we must identify well-tolerated, gene-specific drugs
      that are collectively effective against a wide diversity of gene targets.
      Finally, we must develop protocols by which individual patients are matched with
      appropriate, gene-targeted drugs in a clinically relevant time frame. While these
      may seem like difficult tasks, we are fortunate to have a wide variety of new and
      rapidly evolving research tools at our disposal. These include next-generation
      sequencing of the genome and transcriptome, single nucleotide polymorphism
      (SNP)/copy number variations (CNV) and gene expression microarrays, and RNAi
      libraries for the application of functional screens. In this review we discuss
      the advantages and disadvantages of each of these techniques with the goal of
      demonstrating that no single technique will be sufficient as a standalone
      technology, but rather it will be the integration of all techniques that will
      enable broad application of gene-targeted cancer therapies.

PMID- 23556082
TI  - The Importance of Previous CT Scans in the Diagnosis of Invasive Pulmonary
      Aspergillosis.

PMID- 23556081
TI  - Long-term survivorship at a price: late-term, therapy-associated toxicities in
      the adult hodgkin lymphoma patient.
AB  - There have been an increasing number of survivors of successful treatment of
      Hodgkin lymphoma (HL) over the past 30 years. Although these survivors may be
      cured of their HL, long-term morbidity and mortality are associated with late
      toxicities of treatment. Identification of these late complications will lead to
      strategies to manage them when they occur and hopefully to decrease the risk of
      their development. Second malignancies followed by cardiovascular disease are the
      leading causes of late morbidity and mortality. Musculoskeletal difficulties,
      endocrine abnormalities including sterility and thyroid disease, heart and lung
      damage, persistent fatigue and psychosocial distress have also been seen. The
      subjects of this review are the late complications of primary treatment of HL and
      autologous stem cell transplantation, usually for relapsed disease.

PMID- 23556080
TI  - Prognostic Significance of Treatment Response in CML in View of Current
      Recommendations for Treatment and Monitoring.
AB  - The use of small-molecule kinase inhibitors has redefined the management of
      cancer. Chronic myelogenous leukaemia (CML) has become the paradigm for targeted
      cancer treatment. Imatinib has become the gold standard in the treatment of CML
      with excellent and durable responses and minimal side effects. Molecular
      diagnostics constitute an integral part of the routine monitoring. Results of
      cytogenetic analysis and quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) indicate suboptimal response or treatment failure and guide
      treatment. New Abl kinase inhibitors such as nilotinib or dasatinib are options
      after the failure of or intolerance to imatinib, and both are available for first
      line treatment of newly diagnosed CML. This review focuses on the prognostic
      significance of achieving a response at specific time points in patients with CML
      treated with imatinib, nilotinib or dasatinib in view of available data and
      current treatment recommendations.

PMID- 23556083
TI  - Editorial.

PMID- 23556084
TI  - Symptom Burden and Quality of Life in Patients with Follicular Lymphoma
      undergoing Maintenance Treatment with Rituximab Compared with Observation.
AB  - BACKGROUND: The impact on health related quality of life (HRQoL) of rituximab
      maintenance (R-M) versus observation (OBS) after induction for treatment of
      follicular lymphoma (FL) is unclear. METHODS: We reviewed the charts of 137
      patients (53% female, 87% White, age 61.0 +/- 12.4 years) who received either R-M
      (n = 53) or OBS (n = 84) after chemotherapy induction for newly diagnosed FL at
      community oncology practices within the US. Patients (65% with advanced disease;
      48% with a high FLIPI score [3-5]) had completed >=1 Patient Care Monitor HRQoL
      survey in the period following front-line therapy, and were excluded if they had
      progressed during front-line therapy. RESULTS: Linear mixed models showed that
      postinduction, most symptoms were stable, with patients on R-M reporting HRQoL
      that was equal to that reported by OBS patients. CONCLUSIONS: Among R-M patients,
      receipt of rituximab was associated with improved psychological symptoms.

PMID- 23556085
TI  - High Prevalence of Obesity in Acute Promyelocytic Leukemia (APL): Implications
      for Differentiating Agents in APL and Metabolic Syndrome.
AB  - BACKGROUND: Between January 1999 and December 2008, 469 patients treated for
      acute myeloid leukemia (AML) were included in this single-institution study.
      METHODS: We performed a case-control analysis to study the rate of obesity among
      patients with acute promyelocytic leukemia (APL) and non-APL AML. RESULTS: A
      total of 81% of APL patients analyzed were obese compared with 41.7% in the non
      APL group (p < 0.001). Body mass index (BMI) >30 was seen in 57% of APL patients
      compared with 31% for the non-APL group (p = 0.01). Neither obesity nor the
      chemotherapy dosing based on ideal body weight affected survival. CONCLUSIONS:
      Our findings generate the hypothesis that APL and metabolic syndromes may share a
      common pathogenic pathway via retinoic acid receptors (RARs), the ligand
      controlled transcription factors that function as heterodimers with retinoid X
      receptors (RXRs) to regulate cell growth and survival. If this link is confirmed
      in larger studies, our data will instigate further studies using RXR and RAR
      modulators as a preventive strategy among obese individuals.

PMID- 23556086
TI  - Treatment options for high-risk chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in the
      Western world. The natural history of CLL is extremely variable with a survival
      time from initial diagnosis that ranges from 2 to more than 20 years.
      Understanding the clinical diversity and allowing the subclassification of CLL
      into various prognostic groups not only assists in predicting future outcome for
      patients, but also helps to direct treatment decisions. Chlorambucil and
      fludarabine were the standard therapy for CLL for decades. Randomized studies
      have reported superior overall response and progression-free survival (PFS) for
      fludarabine compared with alkylator-based therapy and for the fludarabine
      cyclophospamide (FC) combination over fludarabine alone. More recently the
      addition of rituximab to the FC regimen (R-FC) has shown significant improvement
      in overall response, PFS and overall survival compared with FC alone. However,
      there are patients for whom this regimen still provides less satisfactory
      results. Within the above studies CLL patients who have some of the poorer
      prognostic markers, such as unmutated IgVH genes and/or high beta-2 microglobulin
      (B2M), and those who fail to achieve a minimal residual disease (MRD) negative
      remission are likely to have a shorter PFS compared with those without these
      features. Various strategies have been explored to improve the outcome for such
      patients. These include the addition of agents to a frontline R-FC regimen, use
      of consolidation and consideration of maintenance. The only group that can be
      clearly identified pretreatment for whom conventional fludarabine-based therapies
      produce significantly inferior response rates, PFS and overall survival are the
      patients who harbour a genetic fault; deletion or mutation or a combination of
      deletion and mutation of tumour protein p53 (TP53). TP53 inactivation is a less
      common finding at first treatment but becomes much more common in fludarabine
      refractory patients. Alemtuzumab and high-dose corticosteroids have been shown to
      be effective in this group of CLL patients. Trials combining these two agents
      have shown improved responses, particularly for those patients with bulky nodal
      disease for whom alemtuzumab alone may be insufficient. Since the duration of
      responses remains relatively short, suitable patients should be considered for
      allogeneic stem cell transplantation according to the European Group for Blood
      and Marrow Transplantation (EBMT) guidelines. Furthermore, there are a number of
      other new treatments on the horizon, including humanized antibodies directed
      against novel targets and small-molecule inhibitors.

PMID- 23556089
TI  - Editorial.

PMID- 23556088
TI  - Efficacy and safety of novel anticoagulants compared with established agents.
AB  - Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer
      major advantages over existing agents. The onset of the anticoagulant effect of
      these agents is rapid. Each agent has a predictable anticoagulant response that
      eliminates the need for monitoring. Clinical trials have been completed with all
      three agents in the prevention and treatment of the three leading causes of
      cardiovascular death: myocardial infarction, stroke, and venous thromboembolism
      (VTE). Novel agents have shown reduced or similar rates of thrombosis, major
      bleeding, and adverse events when weighed against either low molecular weight
      heparin or warfarin. Additional trials are underway and more agents are in
      development. As a result, novel anticoagulants may impact physician prescribing
      practices and warrant consideration in patients requiring thrombosis management.

PMID- 23556087
TI  - Evolving Therapy of Peripheral T-cell Lymphoma: 2010 and beyond.
AB  - The peripheral T-cell lymphomas are a rare, heterogeneous group of non-Hodgkin's
      lymphomas which have an aggressive clinical course. Treatment approaches have
      traditionally been similar to those of diffuse large B-cell lymphomas, but
      outcomes have been inferior. Novel approaches involving agents and pathways
      developed from a better understanding of the biology of the diseases have led to
      therapeutic advances. The introduction of new agents, including antifolates,
      immunoconjugates, histone deacetylase inhibitors, monoclonal antibodies,
      nucleoside analogs, proteasome inhibitors, and signaling inhibitors have improved
      outcomes for patients with relapsed and refractory disease and are being
      incorporated into strategies for first-line therapy. Stem cell transplantation
      remains a potentially curative option for a subset of patients.

PMID- 23556090
TI  - JAK Inhibitors and other Novel Agents in Myeloproliferative Neoplasms: Are We
      Hitting the Target?
AB  - The discovery of somatic mutations in the JAK-STAT signaling pathway was a major
      breakthrough in our understanding of the molecular pathogenesis of the
      myeloproliferative neoplasms (MPNs) polycythemia vera, essential thrombocytosis,
      and primary myelofibrosis. This finding led to the development of small molecule
      inhibitors targeting Janus kinase (JAK) 2 and other JAK family members.
      Currently, there are a number of research and clinical trials ongoing with JAK
      inhibitors. While the appeal of inhibiting JAK2 is clear, studies to date suggest
      that JAK2 inhibitor monotherapy might not be sufficient to cause reductions in
      disease allele burden in MPN patients. There is compelling evidence that JAK
      inhibitors are improving symptoms and therefore quality of life for patients. It
      will be important to investigate the efficacy of JAK inhibitors in preclinical
      and clinical studies to better understand their effects, while at the same time
      pursuing alternative therapies which might offer benefit to MPN patients alone
      and in combination with JAK inhibitors.

PMID- 23556091
TI  - Experimental approaches in the treatment of multiple myeloma.
AB  - Myeloma therapy has undergone significant advances in recent years resulting in a
      marked improvement in survival. Knowledge of the active pathways involved in
      myeloma pathogenesis has led to the discovery of novel agents and greatly
      expanded the potential armamentarium available for treatment. This better
      understanding of the disease and resistance mechanisms has resulted in new agent
      classes that are being evaluated in preclinical and early clinical studies. In
      addition, dosing for existing agents is being optimized, and they are being given
      in new combinations. In this article, we review experimental agents that are
      showing promise in multiple myeloma treatment. New biological agents in clinical
      trials hold the promise of efficacy through novel mechanisms of action, with a
      significant reduction of dose-limiting toxicities compared with classic cytotoxic
      chemotherapeutics. Second-generation proteasome inhibitors and immunomodulatory
      agents are furthest along in clinical development, and histone deacetylase
      inhibitors, heat shock protein 90 inhibitors, Akt inhibitors and monoclonal
      antibodies are some of the other agents entering later-phase clinical trials. We
      also review developments in targeting the myeloma stem cell as an exciting new
      treatment direction.

PMID- 23556095
TI  - Editorial.

PMID- 23556094
TI  - The bone marrow microenvironment in waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoproliferative
      disorder characterized primarily by specific homing and growth of tumor cells
      within the bone marrow niches. The progressive growth of tumor cells throughout
      the bone marrow indicates that the tumor cells are capable of homing and adhering
      to specific niches that allow growth, survival and drug resistance. In this
      review we highlight the interaction of the tumor cells in WM and the bone marrow
      microenvironment including bone marrow stromal cells, endothelial cells and mast
      cells. Migration, adhesion and downstream activation of signaling pathways leads
      to cell trafficking and cell dissemination in WM. Future therapeutic agents need
      to target not only the tumor clone, but also its close interaction with the bone
      marrow microenvironment.

PMID- 23556092
TI  - Invasive fungal infections in acute leukemia.
AB  - Invasive fungal infection (IFI) is among the leading causes for morbidity,
      mortality, and economic burden for patients with acute leukemia. In the past few
      decades, the incidence of IFI has increased dramatically. The certainty of
      diagnosis of IFI is based on host factors, clinical evidence, and microbiological
      examination. Advancement in molecular diagnostic modalities (e.g. non-culture
      based serum biomarkers such as beta-glucan or galactomannan assays) and high
      resolution radiological imaging has improved our diagnostic approach. The early
      use of these diagnostic tests assists in the early initiation of preemptive
      therapy. Nonetheless, the complexity of IFI in patients with leukemia and the
      limitations of these diagnostic tools still mandate astute clinical acumen. Its
      management has been further complicated by the increasing frequency of infection
      by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant
      fungal pathogens. In addition, even though the antifungal armamentarium has
      expanded rapidly in the past few decades, the associated mortality remains high.
      The decision to initiate antifungal treatment and the choice of anti-fungal
      therapy requires careful consideration of several factors (e.g. risk
      stratification, local fungal epidemiologic patterns, concomitant comorbidities,
      drug-drug interactions, prior history of antifungal use, overall cost, and the
      pharmacologic profile of the antifungal agents). In order to optimize our
      diagnostic and therapeutic management of IFI in patients with acute leukemia,
      further basic research and clinical trials are desperately needed.

PMID- 23556093
TI  - Novel targeted treatment strategies for refractory chronic lymphocytic leukaemia.
AB  - Patients with refractory chronic lymphocytic leukaemia (CLL) still have an
      unfavourable prognosis and novel treatment strategies are necessary, preferably
      adjusted to the patient's individual situation. Refractoriness is no longer
      limited just to fludarabine (F) but extends to F-combinations with other
      chemotherapeutic agents (e.g. cyclophosphamide [C] and FC) and antibodies (e.g.
      rituximab [R], FR, and FCR). Also, refractoriness to alemtuzumab is an increasing
      problem. New pharmacological developments provide promising approaches. This
      review focuses on novel therapies such as monoclonal antibodies and small
      molecules aiming at specific targets of the CLL cell in the refractory situation.
      Approved therapeutic regimens will be presented as well as investigational
      approaches. An overview of completed and current clinical trials is offered.

PMID- 23556096
TI  - The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA)
      in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional
      Isomerism.
AB  - BACKGROUND: Chronic Lymphocytic Leukemia (CLL) is not curable in patients that
      are not eligible for allogeneic stem cell transplantation. Therefore, new
      treatment options are highly desirable. Chemically modified nonsteroidal anti
      inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid
      (NO-ASA), have been described to possess antineoplastic capacity. Recently, we
      could demonstrate a potent apoptosis induction in primary CLL cells in vitro and
      tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However,
      little is known about the impact of positional isomerism of NO-ASA on its
      antineoplastic capacity in CLL. METHODS: Primary CLL cells were treated with the
      meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability
      was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter
      Glo luminescence cell viability assay. Caspase and PARP cleavage as well as
      involvement of beta-catenin/Lef-1 signaling was determined by immunoblotting. For
      caspase inhibition, BDTM ApoBlock was used. Nude mice were xenografted with JVM3
      cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. RESULTS: The
      meta-isomer was entirely ineffective in inducing CLL cell apoptosis in
      concentrations up to 100 MUM, while para-NO-ASA acted in the low micromolar
      range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity.
      While para-NO-ASA action involved inhibition of beta-catenin/Lef-1 signaling,
      meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO
      ASA did not significantly reduce tumor growth in a CLL xenograft mouse model,
      while para-NO-ASA was highly potent. CONCLUSION: We conclude that positional
      isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be
      suggested that the para-isomer, but not the meta-isomer, generates a chemical
      structure which is essential for the neoplastic effect of NO-ASA.

PMID- 23556098
TI  - Myeloid sarcoma: current approach and therapeutic options.
AB  - Myeloid sarcoma is a rare disease that can present as an isolated extramedullary
      leukemic tumor, concurrently with or at relapse of acute myeloid leukemia. Owing
      to the rarity of this disorder, most of the literature comprises small
      retrospective studies and case reports. The aim of this review is to summarize
      the current published data regarding the clinical presentation, morphological,
      cytogenetic and molecular features, prognosis and treatment of myeloid sarcoma.

PMID- 23556097
TI  - The rise, fall and subsequent triumph of thalidomide: lessons learned in drug
      development.
AB  - Perhaps no other drug in modern medicine rivals the dramatic revitalization of
      thalidomide. Originally marketed as a sedative, thalidomide gained immense
      popularity worldwide among pregnant women because of its effective anti-emetic
      properties in morning sickness. Mounting evidence of human teratogenicity marked
      a dramatic fall from grace and led to widespread social, legal and economic
      ramifications. Despite its tragic past thalidomide emerged several decades later
      as a novel and highly effective agent in the treatment of various inflammatory
      and malignant diseases. In 2006 thalidomide completed its remarkable renaissance
      becoming the first new agent in over a decade to gain approval for the treatment
      of plasma cell myeloma. The catastrophic collapse yet subsequent revival of
      thalidomide provides important lessons in drug development. Never entirely
      abandoned by the medical community, thalidomide resurfaced as an important drug
      once the mechanisms of action were further studied and better understood. Ongoing
      research and development of related drugs such as lenalidomide now represent a
      class of irreplaceable drugs in hematological malignancies. Further, the
      tragedies associated with this agent stimulated the legislation which revamped
      the FDA regulatory process, expanded patient informed consent procedures and
      mandated more transparency from drug manufacturers. Finally, we review recent
      clinical trials summarizing selected medical indications for thalidomide with an
      emphasis on hematologic malignancies. Herein, we provide a historic perspective
      regarding the up-and-down development of thalidomide. Using PubMed databases we
      conducted searches using thalidomide and associated keywords highlighting
      pharmacology, mechanisms of action, and clinical uses.

PMID- 23556099
TI  - The Role of MicroRNAs in Hematopoietic Stem Cell and Leukemic Stem Cell Function.
AB  - Hematopoietic stem cells (HSCs) are defined by their ability to self-renew and
      reconstitute all elements of the hematopoietic system. Acute myeloid leukemia
      (AML) is thought to arise from, and be maintained by, leukemic stem cells (LSCs),
      which exhibit similar features to HSCs, including the abilities to self-renew and
      differentiate into non-self-renewing cells. Acquisition of stem-cell-like
      characteristics by the LSCs is likely mediated in part by molecular mechanisms
      that normally regulate HSC function. Thus, understanding the shared and unique
      aspects of the molecular regulation of these cell populations will be important
      to understanding the relationship between normal hematopoiesis and
      leukemogenesis. MicroRNAs (miRNAs) are small noncoding RNAs that act at the
      posttranscriptional level to regulate protein expression. Unfortunately, most
      investigations of the role of miRNAs in normal hematopoiesis have been restricted
      to studies of their effects on lineage commitment in progenitors and mature
      effector cell function, but not on HSCs. Recent studies have identified miRNAs
      that enhance HSC function, and an abundance of profiling studies using primary
      AML samples have identified dysregulated miRNAs that may target genes implicated
      in self-renewal (HOX genes, P53, and PTEN), thus providing a potential link
      between normal and malignant stem cells. While these studies as well as recent in
      vivo models of miRNA-induced leukemogenesis (e.g. miR-29a, miR-125b) suggest a
      role for miRNAs in the development of AML, future studies using serial
      transplantation of primary AML blasts, from both mouse models and primary human
      AML specimens, will be necessary to assess the roles of miRNAs in LSC biology.

PMID- 23556101
TI  - Editorial.

PMID- 23556100
TI  - Emerging new approaches for the treatment of acute promyelocytic leukemia.
AB  - The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined
      with anthracycline-based chemotherapy has revolutionized the prognosis of acute
      promyelocytic leukemia (APL) with more than 90% complete response rates and cure
      rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in
      1990s and progress in the treatment of APL have changed its course from a highly
      fatal to a highly curable disease. Despite the dramatic improvement in clinical
      outcome of APL, treatment failure still occurs due most often to early death.
      Relapse has become increasingly less frequent, most commonly occurring in
      patients with high-risk disease. A major focus of research for the past decade
      has been to develop risk-adapted and rationally targeted nonchemotherapy
      treatment strategies to reduce treatment-related morbidity and mortality to low-
      and intermediate-risk or older patients while targeting more intensive or
      alternative therapy to those patients at most risk of relapse. In this review,
      emerging new approaches to APL treatment with special emhasis on strategies to
      reduce early deaths, risk-adapted therapy during induction, consolidation and
      maintenance, as well as an overview of current and future clinical trials in APL
      will be discussed.

PMID- 23556102
TI  - Ikaros: master of hematopoiesis, agent of leukemia.
AB  - Ikaros is the founding member of a family of zinc finger transcription factors
      whose function during early hematopoietic development is required for
      differentiation into the three major hematopoietic lineages. Ikaros deletions
      have been described in human malignancies, particularly precursor B-cell
      leukemia. Deletions of this transcription factor appear to mediate
      leukemogenesis, although the exact mechanism is unclear. This article reviews the
      structure and function of Ikaros proteins in chromatin remodeling and gene
      expression as well as the current knowledge of Ikaros deletions in human
      malignancies. A new proteomic platform, mass cytometry, is introduced which
      allows measurements of greater than 30 parameters at the single-cell level and
      should thus provide a greater level of detail to unravel the mechanistic
      consequences of Ikaros dysfunction in leukemia.

PMID- 23556103
TI  - The molecular biology of diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) represents the most common type of
      malignant lymphoma. In the last few years, significant progress has been achieved
      in the understanding of the molecular pathogenesis of this entity. Gene
      expression profiling has identified three molecular DLBCL subtypes, termed
      germinal-center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and
      primary mediastinal B-cell lymphoma (PMBL). In this review, we summarize our
      current understanding of the biology of these DLBCL subtypes with a special
      emphasis on novel diagnostic and therapeutic approaches.

PMID- 23556104
TI  - Initial therapy of mantle cell lymphoma.
AB  - Mantle cell lymphoma is a well-recognized distinct clinicopathologic subtype of B
      cell non-Hodgkin lymphoma. The current World Health Organization (WHO)
      classification subdivides this entity into aggressive and other variants. The
      disease has a predilection for older males, and patients typically present at an
      advanced stage with frequent splenomegaly and extranodal involvement including
      bone marrow, peripheral blood, gastrointestinal, and occasional central nervous
      system involvement. Early studies of therapy outcomes in this disease revealed
      that while response rates where high, relapse was expected after a limited period
      of time. Prolonged survival was uncommon, with initial median survival rates
      typically in the 3-4-year range. Those with a high proliferative rate, blastoid
      morphology, and selected clinical features were recognized as having a worse
      prognosis. Therapeutic approaches have diverged into aggressive therapies with
      high response rates and promising progression free survival rates, which may be
      applied to younger healthy patients, and less aggressive approaches. Aggressive
      therapies include intensive chemotherapy alone or chemotherapy followed by
      autologous stem cell transplant, which has been shown to be most effective when
      applied in first remission. Whether these more intense therapies result in
      improved survival as compared with less aggressive therapies is not well
      established. Allogeneic transplant has also been investigated, although high
      treatment-related mortality and the risk of chronic graft versus host disease and
      the relatively advanced age of this patient population have tempered enthusiasm
      for this approach. A number of less aggressive therapies have been shown to
      produce promising results. Consolidation and maintenance strategies are an active
      area of investigation. A number of newer agents have shown promising activity in
      relapsed disease, and are being investigated in the front-line setting. Overall
      survival rates are improving in this disease, with current studies suggesting a
      median survival of 5 or more years.

PMID- 23556107
TI  - Editorial.

PMID- 23556105
TI  - Therapeutic options in post-transplant lymphoproliferative disorders.
AB  - Post-transplantation lymphoproliferative disorders (PTLD) are the second most
      frequent malignancies after solid organ transplantation and cover a wide spectrum
      ranging from polyclonal early lesions to monomorphic lymphoma. Available
      treatment modalities include immunosuppression reduction, immunotherapy with anti
      B-cell monoclonal antibodies, chemotherapy, antiviral therapy, cytotoxic T-cell
      therapy as well as surgery and irradiation. Owing to the small number of cases
      and the heterogeneity of PTLD, current treatment strategies are mostly based on
      case reports and small, often retrospective studies. Moreover, many studies on
      the treatment of PTLD have involved a combination of different treatment options,
      complicating the evaluation of individual treatment components. However, there
      has been significant progress over the last few years. Three prospective phase II
      trials on the efficacy of rituximab monotherapy have shown significant complete
      remission rates without any relevant toxicity. A prospective, multicenter,
      international phase II trial evaluating sequential treatment with rituximab and
      CHOP-based chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone)
      is ongoing and preliminary results have been promising. Cytotoxic T-cell therapy
      targeting Epstein-Barr virus (EBV)-infected B cells has shown low toxicity and
      high efficacy in a phase II trial and will be a future therapeutic option at
      specialized centers. Here, we review the currently available data on the
      different treatment modalities with a focus on PTLD following solid organ
      transplantation in adult patients.

PMID- 23556108
TI  - Radiolabeled antibodies directed at CD45 for conditioning prior to allogeneic
      transplantation in acute myeloid leukemia and myelodysplastic syndrome.
AB  - While allogeneic hematopoietic cell transplantation (HCT) may offer the best
      chance of cure for patients suffering from aggressive hematological malignancies
      such as acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic
      syndrome, successful outcomes for the subgroup of patients with high-risk disease
      remain disappointing and lag behind those of lower-risk patients. Because
      relatively high rates of relapse are an important contributor to these poor
      outcomes, efforts have explored approaches to increase the cytotoxic effects of
      treatment. Relapse rates have been shown to improve with the addition of
      increased doses of total body irradiation (TBI) and/or the introduction of
      additional chemotherapy to a HCT conditioning regimen. However, the increase in
      TBI dose and/or additional chemotherapy has also been associated with a
      significant increase in life-threatening toxicities, resulting in no change in
      overall survival. Radioimmunotherapy (RIT) has been employed as an adjunct to HCT
      where targeted delivery of radiation may allow for further escalation of therapy
      to reduce relapse with minimal toxicity. In this review we describe these
      efforts, including the benefits of escalating the dose of radiation to sites of
      hematologic disease prior to HCT, the various cellular targets for antibody
      mediated delivery of radiation, as well as the rationale for incorporation of
      various radionuclides such as alpha emitters and beta emitters into the
      preparative regimen prior to HCT. Lastly, newer novel approaches such as
      pretargeted RIT (PRIT) are described as a method to further increase delivery of
      targeted radiation to hematological tissues while sparing noninvolved organs.

PMID- 23556109
TI  - Anthracycline dose intensification in young adults with acute myeloid leukemia.
AB  - The initial treatment for acute myeloid leukemia (AML) has remained largely
      unchanged for nearly 40 years. Our growing understanding of the molecular
      pathology of AML has resulted in improved measures to risk stratify patients by
      recurrent cytogenetic and molecular abnormalities without marked advancement in
      its initial treatment. The most common regimen consists of a 3-day course of an
      anthracycline and a 7-day infusion of cytarabine. This regimen has been employed
      across the globe in various iterations for many years with modest improvements in
      results yet this remains the first choice for the treatment of younger adults
      with AML. Despite this, the chemotherapeutic agents in this regimen are only now
      being fully understood. Recent evidence has suggested that dose intensification
      of anthracycline in young adults has a significant survival benefit. In this
      paper we review the evidence behind the use of anthracyclines in the initial
      induction of AML in younger adults focusing on the choice and dose of this long
      used drug combination.

PMID- 23556106
TI  - Cellular therapy following allogeneic stem-cell transplantation.
AB  - Allogeneic hematopoietic stem-cell transplantation (HSCT) is the most effective
      approach for many patients with hematologic malignancies. Unfortunately, relapse
      remains the most common cause of death after allogeneic HSCT, and the prognosis
      of relapsed disease is poor for most patients. Induction of a graft-versus
      leukemia (GVL), or graft-versus-tumor, effect through the use of donor leukocyte
      infusion (DLI), or donor lymphocyte infusion, has been remarkably successful for
      relapsed chronic myelogenous leukemia. Unfortunately, response to DLI in other
      hematologic malignancies is much less common and depends on many factors
      including histology, pace and extent of relapse, and time from HSCT to relapse.
      Furthermore, graft-versus-host disease (GVHD) is common after DLI and often
      limits successful immunotherapy. Ultimately, manipulations to minimize GVHD while
      preserving or enhancing GVL are necessary to improve outcomes for relapse after
      allogeneic HSCT.

PMID- 23556110
TI  - Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell
      transplantation.
AB  - From mouse studies to recently published clinical trials, evidence has
      accumulated on the potential use of regulatory T cells (Treg) in preventing and
      treating graft-versus-host disease following hematopoietic-cell transplantation
      (HCT). However, controversies remain as to the phenotype and stability of various
      Treg subsets and their respective roles in vivo, the requirement of antigen
      specificity of Treg to reduce promiscuous suppression, and the molecular
      mechanisms by which Treg suppress, particularly in humans. In this review, we
      discuss recent findings that support a heterogeneous population of human Treg,
      address advances in understanding how Treg function in the context of HCT, and
      present data on recent clinical trials that highlight the feasibility and
      limitations on Treg immunotherapy for graft-versus-host disease.

PMID- 23556111
TI  - Prevention and treatment of venous thromboembolism in patients with cancer.
AB  - Venous thromboembolism (VTE) is the second leading cause of death and a major
      cause of morbidity in patients with cancer. Pharmacologic thromboprophylaxis is
      recommended in all hospitalized cancer patients without contraindications to
      anticoagulants. The role of thromboprophylaxis in outpatients undergoing
      chemotherapy is less certain because of the diversity of the tumor types and
      their associated risks of VTE and bleeding. Thromboprophylaxis should only be
      considered in patients at high risk for VTE. Cancer patients with a newly
      diagnosed VTE should be preferably treated with low-molecular-weight heparin for
      a minimum of 3-6 months. Treatment duration should be individualized based on the
      clinical status and stage of the cancer, the risk of recurrent VTE, the risk of
      bleeding, and personal preference of the patient. Further research is required to
      assess the role of the new oral anticoagulants (direct Xa and thrombin
      inhibitors) for this high-risk population.

PMID- 23556113
TI  - Editorial.

PMID- 23556112
TI  - The importance of hematopoietic progenitor cells in dengue.
AB  - Scientific investigations designed to better understand and assess the
      distinguishing clinical characteristics pave the way to a successful treatment
      for a disease. Since the peripheral blood is obtained easily, the most frequent
      type of investigation performed on infectious agents focuses on the hematological
      components of blood drawn from patients. Bone marrow aspirates, although somewhat
      more difficult to obtain, should be evaluated more frequently because they
      provide additional information, giving us a glimpse into the development of the
      disease. Understanding the distinct and unique changes in hematological
      components of the bone marrow induced by a particular pathogen or corresponding
      to a specific illness may be a valuable asset for the diagnosis and prognosis of
      disease. A good example of a pathogen that could be better evaluated with greater
      knowledge of the bone marrow is dengue, one of the most important public vector
      borne human diseases. Owing to the multitude of clinical manifestations and the
      dynamic alterations of various blood components over time, this disease is one of
      the most difficult to prevent and treat in humans. Although large amounts of data
      have been generated in the literature, there remains a large gap between this
      information and its relevance for the purpose of patient care. While evaluating
      the cellular components in the circulated blood from ill patients provides us
      with valuable information about the pathogenesis of various pathogens, there are
      other players participating in the progression to disease. The goal of this
      review is to emphasize the importance of bone marrow hematopoietic progenitor
      cells in disease and to inspire other researchers to incorporate them into their
      investigations on dengue pathogenesis. It is anticipated that the knowledge
      derived from these investigations not only elicit original concepts on the
      pathogenesis of dengue but also foster a new way of thinking in terms of vaccine
      or therapeutic development to prevent and treat dengue.

PMID- 23556114
TI  - Efficacy of repeat myeloablative chemotherapy with autologous stem-cell support
      in multiple myeloma.
AB  - OBJECTIVE: Induction high-dose chemotherapy followed by myeloablative melphalan
      (HD-Mel) treatment and autologous hematopoietic stem-cell support (autoSCT) is a
      standard treatment for multiple myeloma (MM) either upfront or in relapse after
      conventional treatment. We performed a retrospective analysis of consecutive
      patients undergoing a late repeat HD-Mel/autoSCT treatment for MM. METHODS: Data
      from 24 consecutive patients with MM who underwent a myeloablative treatment with
      HD-Mel late after completion of upfront first high-dose therapy were assessed for
      toxicity, response, progression-free survival (PFS) and time to next treatment
      (TTNT). These data were correlated with the results obtained after the initial
      high dose therapy and autoSCT. RESULTS: A total of 23 patients were treated with
      novel drugs (lenalidomide, thalidomide, bortezomib) after relapse to initial
      autoSCT. The median overall survival (OS) of all patients was 90 months. 19
      patients (79%) achieved a very good partial remission (VGPR) or complete
      remission (CR) after initial autoSCT, compared with 42% after late autoSCT. PFS
      and TTNT were 19 and 24 months after initial compared with 13 and 21 months after
      late autoSCT. Univariate analysis identified initial response duration and the
      achievement of a CR/VGPR after the initial transplantation to be associated with
      prolonged response after repeat autoSCT. CONCLUSIONS: Our data indicate that late
      high-dose treatment followed by autoSCT is safe and effective after upfront
      intensive treatment, can bridge to allogeneic SCT, and encourage collection of an
      additional graft.

PMID- 23556115
TI  - Recent developments in management of older patients with acute myeloid leukemia.

PMID- 23556116
TI  - Targeted therapies through microRNAs: pulp or fiction?
AB  - With the discovery of post-transcriptional silencing, the idea of targeted
      therapies became an approachable goal. The widespread involvement of microRNAs
      (miRNAs) was thought to be the magic bullet against multiple diseases. However,
      several hurdles, ranging from targeted delivery to side effects still have to be
      resolved. In this review, we discuss recent progress on delivery as well as
      current applications for miRNAs as therapeutic agents.

PMID- 23556119
TI  - Editorial.

PMID- 23556117
TI  - Efficacy and safety of lenalidomide in patients with myelodysplastic syndrome
      with chromosome 5q deletion.
AB  - Myelodysplastic syndrome (MDS) with del(5q) is a unique hematopoietic stem cell
      disease that typically follows an indolent course and demonstrates particular
      sensitivity to lenalidomide, a second-generation immunomodulatory agent. Early
      trials demonstrated rapid and durable responses leading to US Food and Drug
      Administration (FDA) approval in 2005. Definitive confirmatory evidence from a
      large phase III trial was recently published. Other recent advances include a
      better understanding of the pathogenesis of disease including haplodeficiency of
      several candidate genes, and elucidation of the lenalidomide-specific effect on
      two phosphatases ultimately leading to p53 degradation in the erythroid
      progenitors and cell cycle arrest in earlier myeloid progenitors. In this review,
      we describe the pathogenesis of MDS with del(5q), summarize the major clinical
      studies establishing the activity of lenalidomide in this population, discuss
      commonly encountered adverse events, and shed light on practical uses of this
      agent in the clinic.

PMID- 23556118
TI  - Safety and efficacy of subcutaneous formulation of bortezomib versus the
      conventional intravenous formulation in multiple myeloma.
AB  - The discovery of the ubiquitin-proteasome pathway first, and the proteasome
      inhibitors thereafter were not made in the hope of improving the treatment of
      malignant diseases. However, bortezomib, the first in class proteasome inhibitor
      introduced in the clinical practice has contributed to improve the outcome of
      patients with multiple myeloma, at relapse or disease progression as well as
      upfront. The results observed in a large randomized trial (APEX) comparing
      bortezomib and high-dose dexamethasone demonstrated a significant benefit for
      bortezomib in terms of response rate, progression-free and overall survival.
      These results led to bortezomib being approved for use in relapsed and/or
      refractory myeloma patients. Subsequent studies demonstrated that its activity
      could be enhanced in combination with other drugs; and the next step was to move
      to the newly diagnosed patient population; in fact, bortezomib-melphalan
      prednisone (VMP) is approved as a standard of care for newly diagnosed elderly
      patients. However, toxicity, especially peripheral neuropathy, as well as the
      intravenous route required for its administration are the two most significant
      bortezomib-related issues. To try to reduce the peripheral neuropathy, new
      guidelines for its management and the introduction of weekly schedules of
      administration have contributed to significantly decrease its incidence and the
      subcutaneous administration has been recently introduce to avoid the intravenous
      (IV) route. Results obtained in phase I/II and III studies have confirmed that
      subcutaneous administration is feasible and represents an additional step towards
      the optimization of bortezomib use, resulting in a probably more convenient
      method than the IV route that is at least as effective.

PMID- 23556120
TI  - Myelofibrosis 2012: it's complicated.
AB  - Major advances in myeloproliferative neoplasms in the last decade have cast light
      on their complexity. The identification of JAK2 (V617F) briefly promised a
      unifying mechanism of pathogenesis with a single pathway that could be
      efficiently targeted. Instead, there have been major advances in understanding
      acquired and background genetic and epigenetic contributors to this group of
      disorders, with refined risk prediction models and experimental therapeutics that
      have provided a more nuanced model of disease. In aggregate these observations
      likely explain the heterogeneity of these disorders and their generally
      unpredictable response to therapy. Molecular studies, beginning with the
      identification of JAK2 (V617F), have led to a concept of MPN subtypes existing on
      a continuum, and additional discoveries such as TET2 and EZH2 mutations have
      provided the molecular underpinnings to begin to explain overlapping phenotypes
      in myeloid malignancies more generally. In many ways the pace of molecular
      discovery is outstripping our ability to integrate these observations into
      clinical care, both in terms of molecular diagnostics and medical decision
      making. This review will attempt to summarize, within a clinical context, our
      evolving understanding of myeloproliferative neoplasms. It focuses on biology,
      histopathology, prognostic scoring systems, stem cell transplantation as well as
      selected clinical/preclinical therapeutic observations.

PMID- 23556121
TI  - Efficacy and safety of reduced-intensity induction therapy with a bortezomib
      based regimen in elderly patients with multiple myeloma.
AB  - The therapeutic effects of bortezomib in untreated and refractory/relapsed
      multiple myeloma have been demonstrated in several clinical trials, displaying
      superiority to the conventional treatments. However, many treatment-related
      toxicities, such as bone marrow suppression, infections and peripheral
      neuropathy, are well known and lead to treatment discontinuation and dose
      modification, especially in elderly patients. The purpose of this review is to
      summarize the published literature concerning the efficacy and safety of reduced
      intensity induction therapy with bortezomib-based regimens in elderly patients
      with multiple myeloma. We used the VISTA trial as a reference and compared it
      with the seven trials identified in a systematic search. The data suggest that
      low-dose bortezomib significantly reduces therapy-related toxicities, especially
      neuropathy, and decreases the rate of discontinuation compared with the twice
      weekly regimen, without losing efficacy. In light of this review, we suggest that
      once-weekly infusion of bortezomib in addition to melphalan-prednisone may be
      considered as a new standard of care in frontline treatment of elderly patients
      with symptomatic multiple myeloma.

PMID- 23556122
TI  - Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic
      immune thrombocytopenia: a review of the efficacy and safety profile.
AB  - Chronic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by
      a low platelet count that has persisted for more than 12 months. Patients may be
      asymptomatic but those with severe disease may have significant morbidity and
      require treatment. Corticosteroids and intravenous immunoglobulin are recommended
      as first-line treatments. Recently, two thrombopoietin-receptor agonists,
      romiplostim and eltrombopag have been licensed for the treatment of chronic ITP.
      The current indications for thrombopoietin-receptor agonists are for
      splenectomized adult patients with chronic ITP who are refractory to other
      treatments and adult nonsplenectomized patients in whom splenectomy is
      contraindicated. This article reviews data on the pharmacology, clinical efficacy
      and safety profile of eltrombopag in the treatment of ITP.

PMID- 23556123
TI  - New treatments in hemophilia: insights for the clinician.
AB  - Hemophilia has evolved from an often fatal hereditary bleeding disorder to a
      disorder for which safe and effective treatment is available. However, there are
      several challenges remaining in the treatment of hemophilia. Prophylaxis to
      prevent bleeding is costly and requires frequent intravenous injections, which
      are cumbersome for patients. Venous access is often difficult to achieve,
      especially in small children where central venous lines may need to be implanted.
      Development of inhibitory antibodies makes treatment of acute bleeds difficult
      and prophylaxis in patients with inhibitors must also be better addressed. In
      order to improve treatment, new products are being developed, some of which are
      already in clinical trials. There are several approaches to prolonging half-lives
      such as PEGylation, Fc fusion and albumin fusion. Increased activity has been
      demonstrated in preclinical trials for factor IX and in a human trial with factor
      VII where the activity of the molecules has been increased by manipulation of the
      molecular composition. Additional approaches, including blockage of inhibitors of
      clotting, are also under investigation. Factor VIII and factor IX gene therapy
      have become a tangible possibility since phase I data recently have been
      published. Results are promising and there is hope that in the near future
      substantial progress will be made, perhaps making hemophilia the first genetic
      condition to be cured.

PMID- 23556124
TI  - The role of intravenous iron in the treatment of anemia in cancer patients.
AB  - Anemia is a major cause of morbidity in cancer patients resulting in poor
      physical performance, prognosis and therapy outcome. Initially, erythropoietin
      stimulating agents (ESAs) were supposed to be the treatment of choice but about
      one third of patients turned out to be nonresponders and meta-analyses provided
      evidence of an increased risk of mortality if used excessively. This along with
      the successful use of intravenous iron for anemia in patients with chronic kidney
      disease prompted seven clinical studies evaluating the efficacy of intravenous
      iron as an adjunct to ESAs and four additional studies using intravenous iron
      only for anemia in cancer patients. These studies confirmed a superior response
      if ESAs are combined with intravenous iron and revealed iron only to be a useful
      option in patients with mild and absolute iron deficiency (AID). Currently, best
      treatment decisions for anemia in cancer might be based on measurements of serum
      ferritin (SF), transferrin saturation (TSAT), soluble transferrin receptor
      (sTfR), ferritin index (FI = sTfR/log SF), hypochromic reticulocytes (CHR) and C
      reactive protein (CRP). However, there is still an urgent need for trials
      investigating diagnostic approaches to optimize therapy of anemia in cancer
      patients with iron and/or ESAs.

PMID- 23556125
TI  - HIV stroke risk: evidence and implications.
AB  - An estimated 34 million men, women, and children are infected with human
      immunodeficiency virus type 1 (HIV-1), the virus that causes acquired
      immunodeficiency syndrome (AIDS). Current technology cannot eradicate HIV-1, and
      most patients with HIV-1-infection (HIV+) will require lifelong treatment with
      combined antiretroviral therapy (cART). Stroke was recognized as a complication
      of HIV-1 infection since the early days of the epidemic. Potential causes of
      stroke in HIV-1 include opportunistic infections, tumors, atherosclerosis,
      diabetes, hypertension, autoimmunity, coagulopathies, cardiovascular disease, and
      direct HIV-1 infection of the arterial wall. Ischemic stroke has emerged as a
      particularly significant neurological complication of HIV-1 and its treatment due
      to the aging of the HIV+ population, chronic HIV-1 infection, inflammation, and
      prolonged exposure to cART. New prevention and treatment strategies tailored to
      the needs of the HIV+ population are needed to address this issue.

PMID- 23556126
TI  - Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use.
AB  - Irritable bowel syndrome (IBS) is the most common functional bowel disease that
      affects up to 15% of the US population. The majority of patients with IBS have
      significant bloating and gas. Recent evidence is beginning to suggest that
      patients with IBS may have an alteration in the gastrointestinal flora.
      Specifically, findings suggest that patients with IBS have excessive bacteria in
      the small bowel, referred to as bacterial overgrowth. Therefore there may be
      benefits of antibiotic-based therapies for IBS. Rifaximin is a nonabsorbable
      antibiotic that demonstrates no clinically relevant bacterial resistance. Some
      studies have demonstrated the efficacy and durable improvement of IBS symptoms
      after treatment with rifaximin. In this review we explore the current data
      showing the association of small intestinal bacterial overgrowth (SIBO) and IBS
      as well as review the available data on the clinical use of rifaximin in the
      treatment of SIBO in patients with IBS.

PMID- 23556128
TI  - Pulsed electron double resonance in structural studies of spin-labeled nucleic
      acids.
AB  - This review deals with the application of the pulsed electron double resonance
      (PELDOR) method to studies of spin-labeled DNA and RNA with complicated spatial
      structures, such as tetramers, aptamers, riboswitches, and three- and four-way
      junctions. The use of this method for studying DNA damage sites is also
      described.

PMID- 23556127
TI  - The management of refractory coeliac disease.
AB  - A significant proportion of patients with coeliac disease are 'nonresponsive' to
      gluten withdrawal. Most cases of nonresponsive coeliac disease are due to
      persisting gluten ingestion. Refractory coeliac disease (RCD) is currently
      defined by persistent symptoms and signs of malabsorption after gluten exclusion
      for 12 months with ongoing intestinal villous atrophy. Primary (without initial
      response to diet) and secondary (relapse following response to diet) RCD is
      recognized. RCD is further classified as type I or type II based on the absence
      or presence of a population of aberrant intestinal lymphocytes. Quality of
      dietetic advice and support is fundamental, and lack of objective corroboration
      of gluten exclusion may result in over-identification of RCD I, particularly in
      those cases with persisting antibody responses. Over-reliance on lymphocyte
      clonality similarly may result in over-diagnosis of RCD II which requires careful
      quantification of aberrant lymphocyte populations. Management of RCD should be
      undertaken in specialist centres. It requires initial intensive dietary
      supervision, strict gluten exclusion and subsequent re-evaluation. There is
      currently insufficient evidence to recommend specific treatments. Steroids are
      often used in both RCD I and II (albeit with little objective evidence of benefit
      in RCD II), and azathioprine as steroid-sparing therapy in RCD I. There is
      growing evidence for the use of cladribine in RCD II with autologous stem cell
      transplantation in nonresponders, but this requires further multicentre
      evaluation. There remains considerable controversy regarding the diagnosis,
      treatment and surveillance of RCD: international consensus in these areas is
      urgently required to facilitate future therapeutic advances.

PMID- 23556129
TI  - Use of transgenic animals in biotechnology: prospects and problems.
AB  - During the past two decades, there have been numerous attempts at using animals
      in order to produce recombinant human proteins and monoclonal antibodies.
      However, it is only recently that the first two therapeutic agents isolated from
      the milk of transgenic animals, C1 inhibitor (Ruconest) and antithrombin (ATryn),
      appeared on the market. This inspires hope that a considerable number of new
      recombinant proteins created using such technology could become available for
      practical use in the near future. In this review, the methods applied to produce
      transgenic animals are described and the advantages and drawbacks related to
      their use for producing recombinant human proteins and monoclonal antibodies are
      discussed.

PMID- 23556130
TI  - Sources of contradictions in the evaluation of population genetic consequences
      after the chernobyl disaster.
AB  - The review covers the analysis of our own and published data pertaining to
      population and genetic consequences in various mammalian species under conditions
      of high levels of ionizing radiation as a result of the Chernobyl accident. The
      findings indicate that these conditions have promoted the reproduction of
      heterozygotes in polyloci spectra of molecular genetic markers and animals with a
      relatively increased stability of the chromosomal apparatus. The prospects of
      using the reproductive "success" of the carriers of these characteristics as an
      integral indicator of the selective influence of environmental stress factors are
      discussed.

PMID- 23556131
TI  - Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV
      1 Integrase Inhibitors.
AB  - Human immunodeficiency virus type 1 integrase is one of the most attractive
      targets for the development of anti-HIV-1 inhibitors. The capacity of a series of
      2,1,3-benzoxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) selected
      using the PASS software to inhibit the catalytic activity of HIV-1 integrase was
      studied in the present work. Only the nitro-derivatives of these compounds were
      found to display inhibitory activity. The study of the mechanism of inhibition by
      nitro-benzofurazans/benzofuroxans showed that they impede the substrate DNA
      binding at the integrase active site. These inhibitors were also active against
      integrase mutants resistant to raltegravir, which is the first HIV-1 integrase
      inhibitor approved for clinical use. The comparison of computer-aided estimations
      of the pharmacodynamic and pharmacokinetic properties of the compounds studied
      and raltegravir led us to conclude that these compounds show promise and need to
      be further studied as potential HIV-1 integrase inhibitors.

PMID- 23556133
TI  - Overexpression of MRPS18-2 in Cancer Cell Lines Results in Appearance of
      Multinucleated Cells.
AB  - Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular
      gene that is located on the human chromosome 6p21.3. We discovered that
      overexpression of the S18-2 protein led to immortalization and de-differentiation
      of primary rat embryonic fibroblasts. Cells showed anchorage-independent growth
      pattern. Moreover, pathways characteristic for rapidly proliferating cells were
      upregulated then. It is possible that the S18-2 overexpression induced
      disturbance in cell cycle regulation. We found that overexpression of S18-2
      protein in human cancer cell lines led to an appearance of multinucleated cells
      in the selected clones.

PMID- 23556132
TI  - Recombinant human butyrylcholinesterase as a new-age bioscavenger drug:
      development of the expression system.
AB  - Butyrylcholinesterase (BChE) is a serine hydrolase (EC 3.1.1.8) which can be
      found in most animal tissues. This enzyme has a broad spectrum of efficacy
      against organophosphorus compounds, which makes it a prime candidate for the role
      of stoichiometric bioscavenger. Development of a new-age DNA-encoded bioscavenger
      is a vival task. Several transgenic expression systems of human BChE were
      developed over the past 20 years; however, none of them has been shown to make
      economic sense or has been approved for administration to humans. In this study,
      a CHO-based expression system was redesigned, resulting in a significant increase
      in the production level of functional recombinant human butyrylcholinesterase as
      compared to the hitherto existing systems. The recombinant enzyme was
      characterized with Elman and ELISA methods.

PMID- 23556134
TI  - Genetic Diversity of Bacillus thuringiensis from Different Geo-Ecological Regions
      of Ukraine by Analyzing the 16S rRNA and gyrB Genes and by AP-PCR and saAFLP.
AB  - The Bacillus cereus group consists of closely related species of bacteria and is
      of interest to researchers due to its importance in industry and medicine.
      However, it remains difficult to distinguish these bacteria at the intra- and
      inter-species level. Bacillus thuringiensis (Bt) is a member of the B. cereus
      group. In this work, we studied the inter-species structure of five
      entomopathogenic strains and 20 isolates of Bt, which were collected from
      different geo-ecological regions of Ukraine, using various methods: physiological
      and biochemical analyses, analysis of the nucleotide sequences of the 16S rRNA
      and gyrB genes, by AP-PCR (BOX and ERIC), and by saAFLP. The analysis of the 16S
      rRNA and gyrB genes revealed the existence of six subgroups within theB.cereus
      group: B anthracis, B. cereus I and II, Bt I and II, and Bt III, and confirmed
      that these isolates belong to the genus Bacillus. All strains were subdivided
      into 3 groups. Seventeen strains belong to the group Bt II of commercial,
      industrial strains. The AP-PCR (BOX and ERIC) and saAFLP results were in good
      agreement and with the results obtained for the 16S rRNA and gyrB genes. Based on
      the derived patterns, all strains were reliably combined into 5 groups.
      Interestingly, a specific pattern was revealed by the saAFLP analysis for the
      industrial strain Bt 0376 r.o., which is used to produce the entomopathogenic
      preparation "STAR-t".

PMID- 23556135
TI  - Bath salts-induced psychosis: a case report.

PMID- 23556136
TI  - "Meow meow" (mephedrone) and catatonia.

PMID- 23556137
TI  - Regarding "A Risperidone-induced Prolactinoma Resolved When A Woman with
      Schizoaffective Disorder Switched to Ziprasidone: A Case Report".

PMID- 23556138
TI  - CNS sites cooperate to detect duplicate subjects with a clinical trial subject
      registry.
AB  - OBJECTIVE: To report the results of the first 1,132 subjects in a pilot project
      where local central nervous system trial sites collaborated in the use of a
      subject database to identify potential duplicate subjects. METHOD: Central
      nervous system sites in Los Angeles and Orange County, California, were contacted
      by the lead author to seek participation in the project. CTSdatabase, a central
      nervous system-focused trial subject registry, was utilized to track potential
      subjects at pre-screen. Subjects signed an institutional review board-approved
      authorization prior to participation, and site staff entered their identifiers by
      accessing a website. Sites were prompted to communicate with each other or with
      the database administrator when a match occurred between a newly entered subject
      and a subject already in the database. RESULTS: Between October 30, 2011, and
      August 31, 2012, 1,132 subjects were entered at nine central nervous system
      sites. Subjects continue to be entered, and more sites are anticipated to begin
      participation by the time of publication. Initially, there were concerns at a few
      sites over patient acceptance, financial implications, and/or legal and privacy
      issues, but these were eventually overcome. Patient acceptance was estimated to
      be above 95 percent. Duplicate Subjects (those that matched several key
      identifiers with subjects at different sites) made up 7.78 percent of the sample
      and Certain Duplicates (matching identifiers with a greater than 1 in 10 million
      likelihood of occurring by chance in the general population) accounted for 3.45
      percent of pre-screens entered into the database. Many of these certain
      duplicates were not consented for studies because of the information provided by
      the registry. CONCLUSION: The use of a clinical trial subject registry and
      cooperation between central nervous system trial sites can reduce the number of
      duplicate and professional subjects entering clinical trials. To be fully
      effective, a trial subject database could be integrated into protocols across
      pharmaceutical companies, thereby mandating site participation and increasing the
      likelihood that duplicate subjects will be removed before they enter (and
      negatively affect) clinical trials.

PMID- 23556139
TI  - Psychotherapy and pharmacotherapy for patients with dissociative identity
      disorder.
AB  - There is a wide variety of what have been called "dissociative disorders,"
      including dissociative amnesia, dissociative fugue, depersonalization disorder,
      dissociative identity disorder, and forms of dissociative disorder not otherwise
      specified. Some of these diagnoses, particularly dissociative identity disorder,
      are controversial and have been questioned by many clinicians over the years. The
      disorders may be under-diagnosed or misdiagnosed, but many persons who have
      experienced trauma report "dissociative" symptoms. Prevalence of dissociative
      disorders is unknown, but current estimates are higher than previously thought.
      This paper reviews clinical, phenomenological, and epidemiological data regarding
      diagnosis in general, and illustrates possible treatment interventions for
      dissociative identity disorder, with a focus on psychotherapy interventions and a
      review of current psychopharmacology recommendations as part of a comprehensive
      multidisciplinary treatment plan.

PMID- 23556140
TI  - Adjunctive Methylphenidate in the Treatment of Bulimia Nervosa Co-occurring with
      Bipolar Disorder and Substance Dependence.
AB  - Bulimia nervosa is associated with bipolar disorder, substance dependence,
      attention-deficit hyperactivity disorder, and anxiety disorders. Few reports,
      however, have addressed the treatment of patients with all of these conditions.
      We describe a young woman with bulimia nervosa, bipolar I disorder, cocaine and
      alcohol dependence, attention-deficit hyperactivity disorder, and panic disorder
      who achieved a sustained (>1 year) remission of her bulimia nervosa symptoms and
      significant improvement of her attention-deficit hyperactivity disorder symptoms
      with adjunctive methylphenidate after her bipolar, substance use, and panic
      disorders were successfully treated with hospitalization, intensive
      psychotherapy, quetiapine, and lamotrigine. Further research into the use of
      stimulants in bulimia nervosa, including in patients with complex comorbidity, is
      required.

PMID- 23556142
TI  - Modelled air pollution levels versus EC air quality legislation - results from
      high resolution simulation.
AB  - An appropriate method for evaluating the air quality of a certain area is to
      contrast the actual air pollution levels to the critical ones, prescribed in the
      legislative standards. The application of numerical simulation models for
      assessing the real air quality status is allowed by the legislation of the
      European Community (EC). This approach is preferable, especially when the area of
      interest is relatively big and/or the network of measurement stations is sparse,
      and the available observational data are scarce, respectively. Such method is
      very efficient for similar assessment studies due to continuous spatio-temporal
      coverage of the obtained results. In the study the values of the concentration of
      the harmful substances sulphur dioxide, (SO2), nitrogen dioxide (NO2),
      particulate matter - coarse (PM10) and fine (PM2.5) fraction, ozone (O3), carbon
      monoxide (CO) and ammonia (NH3) in the surface layer obtained from modelling
      simulations with resolution 10 km on hourly bases are taken to calculate the
      necessary statistical quantities which are used for comparison with the
      corresponding critical levels, prescribed in the EC directives. For part of them
      (PM2.5, CO and NH3) this is done for first time with such resolution. The
      computational grid covers Bulgaria entirely and some surrounding territories and
      the calculations are made for every year in the period 1991-2000. The averaged
      over the whole time slice results can be treated as representative for the air
      quality situation of the last decade of the former century. 

PMID- 23556141
TI  - Molecular docking studies of quercetin and its analogues against human inducible
      nitric oxide synthase.
AB  - Nitric oxide synthases (NOS) catalyze to produce nitric oxide (NO) from L
      arginine. The isoform of NOS i.e. inducible nitric oxide synthases (iNOS)
      expression is observed in various human malignant tumors such as breast, lung,
      prostate and bladder, colorectal cancer, and malignant melanoma. Also an
      increased level of iNOS expression and activity has been found in the tumor cells
      of gynecological malignancies, stroma of breast cancer and tumor cells of head
      and neck cancer. Because of its importance in causing tumors and cancer, iNOS
      enzyme has become a new target in finding novel inhibitors as anti cancer agents.
      The present work focuses on the molecular docking analysis of quercetin and its
      analogues against iNOS enzyme. Earlier there are reports of quercetin inhibiting
      iNOS enzyme in certain experiments as anti cancer agent. But the clinical use of
      quercetin is limited by its low oral bioavailability and therefore needed its
      molecular modification to improve its pharmacological properties. In the present
      study ten analogues of quercetin were found to be docked at the active site
      cavity with favorable ligand-protein molecular interaction and interestingly from
      the ADME-Toxicity analysis these analogues have enhanced pharmacological
      properties than quercetin. 

PMID- 23556143
TI  - Barriers to rural households' participation in low-skilled off-farm labor
      markets: theory and empirical results from northern Ethiopia.
AB  - Promotion of low-skilled off-farm rural labor market participation can be an
      important strategy to improve livelihoods and food security of the poor in
      developing countries. This paper investigates rural farm households'
      participation in low-skilled off-farm labor markets with disaggregate data from a
      survey of 400 households in Tigray, the northern highlands of Ethiopia. Adopting
      Heckman's two stage approach, we examined households' decisions to participate or
      not in markets by probit model in the first stage and level of participation by
      ordinary least squares procedures in the second stage. The results show that
      households' decision to enter into a labor market significantly depends on the
      characteristics of the households such as sex, age of the household heads and
      labor endowments in the households. Similarly, the level of participation in
      labor markets measured by the amount of off-farm wage income depends on labor
      endowments in the households and the place where the households are located.
      Since cash constrained rural households do not find themselves advantageous to
      participate in off-farm labor markets, the reduction of cash constraint is the
      major policy implication of the paper. This holds true in general for all cash
      constrained rural households in developing countries. Similarly, the empirical
      results in the paper suggest removal of locational barriers to access labor
      markets. This helps them to earn off-farm income. It is necessary to eliminate
      (or at least reduce) obstacles for rural households to enter into a market of off
      farm wage earning activities. This holds true in general for all rural households
      in developing countries. This paper is therefore expected to contribute to frame
      appropriate policy that promotes participation in low-skilled off-farm rural
      labor markets in developing countries where many rural households are not only
      poor but also low-skilled. 

PMID- 23556144
TI  - M-health: supporting automated diagnosis and electonic health records.
AB  - BACKGROUND: Mobile technology has become a part of our everyday life. Mobile
      services are used in a wide variety of scientific areas including healthcare. As
      an intersection of computer supported technology and medicine, m-health is
      expected to bring higher quality in healthcare. A remedy to deter people from
      neglecting their health issues is providing further and targeted information,
      while this information is available on the main devices most people use on a
      regular basis, namely any station or a mobile phone connected to Internet,
      enabling access to their health status anytime and at any place. RESULTS: The
      authors present a framework that is built based on mobile health and which, in
      addition, incorporates a module that is responsible for making diagnoses. To
      achieve this, we have applied the Analytical Hierarchical Process algorithm (AHP)
      on the test results, making the system able to infer the presence or not of an
      illness in the subject. Data to be processed emerge from the corresponding
      subjects' electronic health records. Through the resulting system, doctors and
      health companies, which are involved in medical sciences, are offered a
      sophisticated, powerful tool that provides supplementary diagnoses about their
      clients by employing their laboratory medical tests. CONCLUSIONS: In this paper a
      novel computer supported framework is presented, which is targeted basically in
      the scientific area of mobile health. The incorporated medical diagnosis module
      and the online presentation of medical tests results may not only facilitate
      doctors' and medical agencies work and support healthcare in general, but also
      and most importantly can benefit users by having an analytical picture of their
      health status at any place and time. Perhaps one of the most challenging targets
      for this system to reach is to draw individuals' attention and give them motives
      to be more concerned about their health.

PMID- 23556145
TI  - Unconscious learning processes: mental integration of verbal and pictorial
      instructional materials.
AB  - This review aims to provide an insight into human learning processes by examining
      the role of cognitive and emotional unconscious processing in mentally
      integrating visual and verbal instructional materials. Reviewed literature shows
      that conscious mental integration does not happen all the time, nor does it
      necessarily result in optimal learning. Students of all ages and levels of
      experience cannot always have conscious awareness, control, and the intention to
      learn or promptly and continually organize perceptual, cognitive, and emotional
      processes of learning. This review suggests considering the role of unconscious
      learning processes to enhance the understanding of how students form or activate
      mental associations between verbal and pictorial information. The understanding
      would assist in presenting students with spatially-integrated verbal and
      pictorial instructional materials as a way of facilitating mental integration and
      improving teaching and learning performance. 

PMID- 23556146
TI  - Edge-interior differences in the species richness and abundance of drosophilids
      in a semideciduous forest fragment.
AB  - Habitat fragmentation is the main cause of biodiversity loss, as remnant
      fragments are exposed to negative influences that include edge effects,
      prevention of migration, declines in effective population sizes, loss of genetic
      variability and invasion of exotic species. The Drosophilidae (Diptera),
      especially species of the genus Drosophila, which are highly sensitive to
      environmental variation, have been used as bioindicators. A twelve-month field
      study was conducted to evaluate the abundance and richness of drosophilids in an
      edge-interior transect in a fragment of semideciduous forest in Sao Paulo State,
      Brazil. One objective of the study was to evaluate the applied methodology with
      respect to its potential use in future studies addressing the monitoring and
      conservation of threatened areas. The species abundance along the transect showed
      a clear gradient, with species associated with disturbed environments, such as
      Drosophila simulans, Scaptodrosophila latifasciaeformis and Zaprionus indianus,
      being collected at the fragment edge and the species D. willistoni and D.
      mediostriata being found in the fragment's interior. Replacement of these species
      occurred at approximately 60 meters from the edge, which may be a reflection of
      edge effects on species abundance and richness because the species found within
      the habitat fragment are more sensitive to variations in temperature and humidity
      than those sampled near the edge. The results support the use of this methodology
      in studies on environmental impacts. 

PMID- 23556147
TI  - Integrin triplets of marine sponges in the murine and human MHCI-CD8 interface
      and in the interface of human neural receptor heteromers and subunits.
AB  - Based on our theory, main triplets of amino acid residues have been discovered in
      cell-adhesion receptors (integrins) of marine sponges, which participate as
      homologies in the interface between two major immune molecules, MHC class I
      (MHCI) and CD8alphabeta. They appear as homologies also in several human neural
      receptor heteromers and subunits. The obtained results probably mean that neural
      and immune receptors also utilize these structural integrin triplets to form
      heteromers and ion channels, which are required for a tuned and integrated
      intracellular and intercellular communication and a communication between cells
      and the extracellular matrix with an origin in sponges, the oldest multicellular
      animals. 

PMID- 23556155
TI  - Can we reverse Alzheimer's?  New approaches from Harvard offer hope.

PMID- 23556148
TI  - The effects of arthritis, mobility, and farm task on injury among older farmers.
AB  - The current study was conducted by performing secondary analysis of data drawn
      from a study of sustained work indicators of older farmers. The primary outcome
      variable was the reported occurrence or non-occurrence of injuries because of
      farm work in the past year. There were three explanatory variables of interest:
      (1) whether respondents reported ever having been diagnosed with
      arthritis/rheumatism by a medical doctor; (2) whether participants reported
      having mobility problems; and (3) a farm task injury risk index. Additional
      explanatory variables included the estimated number of days spent on farming
      activities in the past year, as well as demographic characteristics such as age,
      sex, and race. Institutional review board approvals were obtained for the
      original study prior to data collection, and for the current study prior to
      secondary analysis of data. Descriptive statistics were calculated for the
      outcome and explanatory variables. Initial multivariable longitudinal models for
      the occurrence of injuries were fitted with the explanatory variables. Odds
      ratios for the effects of interest were calculated using the final models. A
      longitudinal model was fitted using data in waves 1, 3, and 5, with a farm task
      injury risk index as outcome variable and wave, sex, age, race, and estimated
      number of days spent on farming activities in the past year as explanatory
      variables for exploration of the relationship between the farm task injury risk
      index and these variables. In this group of older farmers, aging was protective
      for injury, and was associated with decreased farm task injury risk index.
      Arthritis/rheumatism was associated in our study with occurrence of injury
      because of farm work across all four waves. Our results indicated that farmers
      with mobility problems were twice as likely to experience injuries because of
      farm work compared to farmers with no mobility problems. Increased farm task
      injury risk index was associated with a 40% increase in odds for the occurrence
      of injury due to farm work. In this study of older farmers, the type of work, and
      not the amount of work was significantly associated with injury risk.
      Implications for future studies of farm injury include the need for nurse
      researchers and others to incorporate objective validated measures of mobility
      and health care provider diagnoses of arthritis, and arthritis type. Nurse
      researchers should proceed with ongoing evaluation of the farm task injury risk
      index to determine its validity, reliability, and usefulness as a predictor of
      farm injuries. In the practice setting, nurses may apply findings from this study
      to provide injury prevention teaching to older farmers and their families. For
      example, discussions of the more risky farm tasks, injury prevention strategies,
      and treatment modalities including those that promote improved mobility should be
      targeted to older farmers with arthritis and actual or potential mobility issues.
      Ultimately, these nursing research and practice efforts may lead to preservation
      of function, and decreased injury risk and severity among older farmers.

PMID- 23556156
TI  - Five things to do this month.

PMID- 23556157
TI  - Ask the doctor.  At what percentage of blockage of the carotid artery do you
      consider surgery?  I am a 73-year-old man with a 70% blockage, and my doctor says
      to wait a year and check back then.

PMID- 23556158
TI  - Ask the doctor. I live at 6,000 feet of altitude and am 67 years old. Does
      exercising at that high an altitude confer any additional health benefits,
      especially for the cardiovascular system?

PMID- 23556159
TI  - Are high tech heart tests best?  Some popular heart imaging tests aren't for
      everyone.

PMID- 23556160
TI  - Depression and obesity: confirming the link.  Small effort can lead to big
      changes.

PMID- 23556161
TI  - NSAIDs: topicals vs. pills for pain.  Topicals aren't as popular, but they can be
      very effective.

PMID- 23556162
TI  - Why doctors keep pushing fiber.  Easy ways to pump more into your diet.

PMID- 23556163
TI  - Considering testosterone therapy?  35% of men over 45 may have low testosterone
      levels.

PMID- 23556164
TI  - Should you get a PSA test?  The latest thinking on this controversial screening.

PMID- 23556165
TI  - The popular fix for droopy eyes.  When is surgery warranted?

PMID- 23556166
TI  - New attack on precancerous patches.  58 million of us have actinic keratoses. 
      Now treatment is easier.

PMID- 23556167
TI  - Beans may help control blood sugar in people with diabetes.

PMID- 23556168
TI  - Aspirin may help colon cancer patients live longer.

PMID- 23556169
TI  - Bisphosphonates may help men with osteoporosis.

PMID- 23556171
TI  - [Impact of radical resection in the complex treatment of patients with malignant
      solid tumors].

PMID- 23556170
TI  - [Non-surgical periodontal treatment in uncontrolled type 2 diabetes mellitus
      patients].
AB  - OBJECTIVE: To evaluate the effect of non-surgical periodontal treatment on the
      metabolic control, measured by HbA1c in uncontrolled type 2 diabetes mellitus
      patients with periodontal disease treated with the ADA-EASD algorithm. METHODS:
      The study group consisted of 38 patients diagnosed with type 2 diabetes mellitus
      and periodontal disease, attending a benefit clinic. HbA1c measures were obtained
      before and after 3 months of the non-surgical periodontal treatment. T student
      test for dependent samples was applied with a p value less than 0.05 for
      statistical significance. RESULTS: From the total sample, 79% was female, and
      mean age was of 51 +/- 9.8 years old. Mean HbA1c at baseline was of 8.6 and 8% at
      exit. The mean reduction was statistically significant (p = 0.026). After non
      surgical periodontal treatment, the prevalence of periodontal disease was of 8%.
      The mean of personal plaque control before and after the treatment decreased from
      82.6% to 35.5% (p < 0.000). CONCLUSIONS: Consistent with similar previous
      studies, in this study we demonstrate progress in glycemic control, remission of
      periodontal disease and improved personal plaque control.

PMID- 23556172
TI  - Pediatric endocrinology.

PMID- 23556173
TI  - Sinus endoscopy.

PMID- 23556174
TI  - Cardiac catheterization.

PMID- 23556175
TI  - Percutaneous ASD/PFO closure.

PMID- 23556176
TI  - Transplant hepatology.

PMID- 23556177
TI  - Transthoracic echocardiography.

PMID- 23556178
TI  - Biofeedback.

PMID- 23556179
TI  - Gastroenterology.

PMID- 23556180
TI  - Urology.

PMID- 23556181
TI  - Surgical critical care.

PMID- 23556182
TI  - Revised medical criteria for evaluating visual disorders. Final rules.
AB  - We are revising and reorganizing the criteria in the Listing of Impairments
      (listings) that we use to evaluate cases involving visual disorders in adults and
      children under titles II and XVI of the Social Security Act (Act). The revisions
      reflect our program experience and guidance we have issued in response to
      adjudicator questions we have received since we last revised these criteria in
      2006. These revisions will provide clarification about how we evaluate visual
      disorders and ensure more timely adjudication of claims in which we evaluate
      visual disorders that result in a loss of visual acuity or field.

PMID- 23556183
TI  - Grants for transportation of veterans in highly rural areas. Final rule.
AB  - The Department of Veterans Affairs (VA) amends its regulations to establish a new
      program to provide grants to eligible entities to assist veterans in highly rural
      areas through innovative transportation services to travel to VA medical centers,
      and to otherwise assist in providing transportation services in connection with
      the provision of VA medical care to these veterans, in compliance with section
      307 of title III of the Caregivers and Veterans Omnibus Health Services Act of
      2010. This final rule establishes procedures for evaluating grant applications
      under the new grant program, and otherwise administering the new grant program.

PMID- 23556184
TI  - Medicaid program; increased Federal Medical Assistance Percentage changes under
      the Affordable Care Act of 2010. Final rule with request for comments.
AB  - This final rule implements the provisions of the Patient Protection and
      Affordable Care Act of 2010 and the Health Care and Education Reconciliation Act
      of 2010 (collectively referred to as the Affordable Care Act) relating to the
      availability of increased Federal Medical Assistance Percentage (FMAP) rates for
      certain adult populations under states' Medicaid programs. This final rule
      implements and interprets the increased FMAP rates that will be applicable
      beginning January 1, 2014 and sets forth conditions for states to claim these
      increased FMAP rates.

PMID- 23556185
TI  - The cold facts about colds and flu.

PMID- 23556186
TI  - What my patients have taught me.

PMID- 23556187
TI  - Tattoos aren't all butterflies and roses.

PMID- 23556188
TI  - What's in that pork? We found antibiotic-resistant bacteria--and traces of a
      veterinary drug.

PMID- 23556189
TI  - Hospitals still order too many CT scans.

PMID- 23556190
TI  - The red-carpet treatment, for a fee.

PMID- 23556191
TI  - When it pays, literally, to lose weight.

PMID- 23556192
TI  - Lose weight your way: 9000 readers rate 13 diet plans and tools.

PMID- 23556193
TI  - Too much of a good thing.

PMID- 23556194
TI  - California's cancer warning.

PMID- 23556195
TI  - Health reform questions answered.

PMID- 23556197
TI  - Save your life: cancer screening is oversold. Know the tests to get--and those to
      skip.

PMID- 23556198
TI  - [In-vitro fertilization - twin pregnancies: higher risk after artificial
      insemination? ].

PMID- 23556200
TI  - [Perinatal mortality - lower perinatal mortality due to higher rate of late
      preterm births].

PMID- 23556199
TI  - [Prenatal diagnosis - how powerful is DNA microarray compared to karyotyping?].

PMID- 23556201
TI  - [Extreme immaturity - morbidity and mortality of very preterm infants].

PMID- 23556202
TI  - [Low birth weight - increased low birth weight and functional deficits in very
      premature babies?].

PMID- 23556203
TI  - [Respiratory distress syndrome - mortality and neurodevelopmental disorders after
      CPAP vs. surfactant application].

PMID- 23556205
TI  - A good time to focus on the profession's finest.

PMID- 23556204
TI  - Editorial.

PMID- 23556206
TI  - Campaign will aim to eliminate discrimination against BME staff.

PMID- 23556207
TI  - Registration fee to rise again amid calls for monthly payment scheme.

PMID- 23556209
TI  - UCLH creates 500 new nursing posts in bid to cut use of agencies.

PMID- 23556208
TI  - Mid Staffs ward sisters refute bullying and misconduct charges.

PMID- 23556210
TI  - Changes to A&E services leave staff facing an uncertain future.

PMID- 23556211
TI  - Nurse of the Year offers hope to COPD patients.
AB  - The breathing space clinic was set up by Matthew Hodson in 2011, bringing end of
      life care to patients with chronic obstructive pulmonary disease. As nurse of the
      year he hopes to raise the profile of the condition and awareness of care
      options.

PMID- 23556212
TI  - We love amazing Ellie.
AB  - Chemotherapy nurse Ellie Hodge is the winner of the 2013 Claire Rayner patient's
      choice award, organised by Nursing Standard. Ms Hodge is praised for her ability
      to see the individual by former patients who nominated her.

PMID- 23556213
TI  - Joined-up thinking.
AB  - Changes to commissioning being introduced on April 1 are designed to reshape
      services to meet the needs of patients. No one knows if clinical commissioners
      will have the drive to improve co-ordination between health services, but
      supporters of integration say it is a more rewarding way of working and it
      improves care.

PMID- 23556214
TI  - Mind the workplace hazards.
AB  - Expecting nursing staff to work in an unsafe environment puts employees and
      patients at risk of harm. Employers are required by law to protect everyone on
      their premises, but some still fail to comply. This article provides a guide to
      the rights and responsibilities of employers, managers and employees.

PMID- 23556215
TI  - The role of technology and digital gaming in nurse education.
AB  - There is growing evidence that using e-learning and digital gaming technology can
      support students in their learning. An international project, Continuing/Higher
      Education in Research Methods Using Games, funded by the European Commission's
      Lifelong Learning Programme and led by a team at the University of the West of
      Scotland, aims to develop interactive activities and games to support nursing and
      social science students. This article looks at the scope of the project in
      helping to deliver nurse education.

PMID- 23556216
TI  - Dietary approaches to promote bone health in adults.
AB  - Osteoporosis is a major public health issue, affecting around three million
      people in the UK. Several lifestyle factors play a role in the development of the
      condition, including low physical activity, smoking, excess alcohol consumption
      and low intakes of bone health nutrients. The most important of these nutrients
      are vitamin D and calcium, which work in combination to strengthen and stabilise
      bone tissue. However, intake of calcium is low in some people, while vitamin D
      deficiency is widespread. across the age spectrum. This article identifies key
      actions for improving bone health, with a focus on increased intake of beneficial
      nutrients.

PMID- 23556217
TI  - History taking.

PMID- 23556219
TI  - My two lives: on and off deck.

PMID- 23556218
TI  - A chance to ignite ideas.

PMID- 23556220
TI  - Inside information.

PMID- 23556221
TI  - Delivering the self-management message.

PMID- 23556222
TI  - An education in autism.

PMID- 23556223
TI  - Safe blood transfusions on the battlefield.

PMID- 23556224
TI  - Success of malaria-prevention protocol.

PMID- 23556225
TI  - Creative nursing care in the community.

PMID- 23556226
TI  - Bringing dementia strategy to life.

PMID- 23556227
TI  - More freedom and control.

PMID- 23556228
TI  - Creating a 'breathing space'.

PMID- 23556229
TI  - Follow up arthritis care.

PMID- 23556230
TI  - Modernising mental health in Africa.

PMID- 23556231
TI  - Trailblazers in the delivery of good care.

PMID- 23556232
TI  - Workshops for relatives.

PMID- 23556233
TI  - Healing psychological wounds.

PMID- 23556234
TI  - Happier patients and staff.

PMID- 23556235
TI  - The Southeastern Aerosol Research and Characterization (SEARCH) study: temporal
      trends in gas and PM concentrations and composition, 1999-2010.
AB  - The SEARCH study began in mid 1998 with a focus on particulate matter and gases
      in the southeastern United States. Eight monitoring sites, comprising four
      urban/nonurban pairs, are located inland and along the coast of the Gulf of
      Mexico. Downward trends in ambient carbon monoxide (CO), sulfur dioxide (SO2),
      and oxidized nitrogen species (NOy) concentrations averaged 1.2 +/- 0.4 to 9.7 +/
      1.8% per year from 1999 to 2010, qualitatively proportional to decreases of 4.7
      to 7.9% per year in anthropogenic emissions of CO, SO2, and oxides of nitrogen
      (NOx) in the SEARCH region. Downward trends in mean annual sulfate (SO4)
      concentrations ranged from 3.7 +/- 1.1 to 6.2 +/- 1.1% per year approximately
      linear with, but not 1:1 proportional to, the 7.9 +/- 1.1% per year reduction in
      SO2 emissions from 1999 to 2010. The 95th percentile of the March-October peak
      daily 8-hr ozone (O3 concentrations decreased by 1.1 +/- 0.4 to 2.4 +/- 0.6 ppbv
      per year (1.5 +/- 0.6 to 3.1 +/- 0.8% per year); O3 precursor emissions of NOx
      and volatile organic compounds (VOC) decreased at rates of 4.7 and 3.3% per year,
      respectively. Ambient particulate nitrate (NO3) concentrations decreased by 0.6
      +/- 1.2 to 5.8 +/- 0.9% per year modulated in comparison with mean annual ambient
      NOy concentration decreases ranging from 6.0 +/- 0.9 to 9.0 +/- 1.3% per year.
      Mean annual organic matter (OM) and elemental carbon (EC) concentrations declined
      by 3.3 +/- 0.8 to 6.5 +/- 0.3 and 3.2 +/- 1.4 to 7.8 +/- 0.7% per year. The
      analysis demonstrates major improvements in air quality in the Southeast from
      1999 to 2010. Meteorological variations and incompletely quantified uncertainties
      for emission changes create difficulty in establishing unambiguous quantitative
      relationships between emission reductions and ambient air quality. IMPLICATIONS:
      Emissions and secondary pollutants show complex relationships that depend on year
      to-year variations in dispersion and atmospheric chemistry. The observed response
      of 03 to NOx and VOC emissions in the Southeast implies that continuing
      reductions of precursor emissions, probably achieved through vehicle fleet
      turnover and emission control measures, will be needed to attain the National
      Ambient Air Quality Standard for O3. Reductions in fine particle concentrations
      have resulted from reductions of primary PM, especially EC and a portion of OM,
      and from reduction of gas precursors known to form particles, especially SO4 from
      SO2. Continued reduction of PM2.5 mass concentrations will require attention to
      organic constituents, which may be complicated by potentially unmanageable
      biogenic species present in the Southeast.

PMID- 23556236
TI  - The Southeastern Aerosol Research and Characterization (SEARCH) study: spatial
      variations and chemical climatology, 1999-2010.
AB  - The Southeastern Aerosol Research and Characterization (SEARCH) study, which has
      been in continuous operation from 1999 to 2012, was implemented to investigate
      regional and urban air pollution in the southeastern United States. With
      complementary data from other networks, the SEARCH measurements provide key
      knowledge about long-term urban/nonurban pollution contrasts and regional
      climatology affecting inland locations and sites along the Gulf of Mexico
      coastline. Analytical approaches ranging from comparisons of mean concentrations
      to the application of air mass trajectories and principal component analysis
      provide insight into local and area-wide pollution. Gases (carbon monoxide,
      sulfur dioxide, nitrogen oxides, ozone, and ammonia), fine particle mass
      concentration, and fine particle species concentrations (including sulfate,
      elementary carbon, and organic carbon) are affected by a combination of regional
      conditions and local emission sources. Urban concentrations in excess of regional
      baselines and intraurban variations of concentrations depend on source proximity,
      topography, and local meteorological processes. Regional-scale pollution events
      (95th percentile concentrations) involving more than 6 of the 8 SEARCH sites are
      rare (< 2% of days), while subregional events affecting 4-6 sites occur on
      approximately 10% of days. Regional and subregional events are characterized by
      widely coincident elevated concentrations of ozone, sulfate, and particulate
      organic carbon, driven by persistent synoptic-scale air mass stagnation and
      higher temperatures that favor formation of secondary species, mainly in the
      summer months. The meteorological conditions associated with regional stagnation
      do not favor long-range transport of polluted air masses during episodes.
      Regional and subregional pollution events frequently terminate with southward and
      eastward penetration of frontal systems, which may initially reduce air pollutant
      concentrations more inland than along the Gulf Coast. IMPLICATIONS: Regional
      distribution of emission sources and synoptic-scale meteorological influences
      favoring stagnation lead to high regionwide pollution levels. The regional
      influence is greatest with secondary species, including ozone (03) particulate
      sulfate (SO4), and particulate organic matter, some of which is produced by
      atmospheric oxidation of volatile organic compounds (VOCs) from vegetation and
      anthropogenic sources. Other species, many of which are from primary emissions,
      are more influenced by local sources, especially within the Atlanta, GA, and
      Birmingham, AL, metropolitan areas. Limited measurements of modern and fossil
      total carbon point to the importance of biological and biogenic emissions in the
      Southeast.

PMID- 23556237
TI  - Identification of nitrous oxide emissions from green areas of Chihuahua City
      irrigated with treated wastewater.
AB  - Since 2000, the city of Chihuahua had a distribution system of treated wastewater
      for irrigation of green areas and has replaced this water for processes that do
      not require the consumption of drinking water. This replacement was necessary in
      order to meet the growing demand for potable water which has exceeded the current
      supply of 700 L (184,88 gallons) per second. Nowadays it is necessary to identify
      and assess the risks to public health and the environment due to the substitution
      of drinking water by treated wastewater in the last 10yr. Treated wastewater
      contains compounds whose effects have not been evaluated when used for irrigation
      in public green areas. Therefore, it is not known whether there is a danger to
      the health of park visitors due to exposure and/or inhalation of the emitted
      gases, accidental ingestion of water, or impact to the environment. The purpose
      of the research, using an experimental prototype, is to identify the changes from
      nitrogen present in the treated wastewater to nitrous oxide. The research
      objective is the generation of data to simulate a regional scale at this stage,
      which will be analyzed and statistically validated using Minitab and Origin
      software. The experiment was performed using three different samples to compare
      water quality: drinking water treated wastewater, and water with nitrogen-based
      fertilizer (urea). Prototypes were filled with two types of soil: sand and clay
      Each type of water was sprinkled on the prototype, grass was planted in it, and
      the prototype was equipped with samplers to capture the gas in the root zone. The
      authors found high emissions of nitrous oxide in the clay-filled lysimeters, and
      climate and growing conditions of vegetation were the most important factors for
      producing nitrous oxide. IMPLICATIONS: Major problems in the ecosystem arise from
      solutions that are not based on environmental public policy research or
      experimentation. For example, before application a specific policy or regulation,
      research should be performed to evaluate long term effects to the ecosystem and
      this can be done through close monitoring. This study raises awareness about the
      public policy of substituting potable water with treated wastewater for
      irrigation of green areas in Chihuahua City. The present study was performed
      during a sufficient period of time in order to assess the impact to the
      environment.

PMID- 23556238
TI  - Measuring in-use ship emissions with international and U.S. federal methods.
AB  - Regulatory agencies have shifted their emphasis from measuring emissions during
      certification cycles to measuring emissions during actual use. Emission
      measurements in this research were made from two different large ships at sea to
      compare the Simplified Measurement Method (SMM) compliant with the International
      Maritime Organization (IMO) NOx Technical Code to the Portable Emission
      Measurement Systems (PEMS) compliant with the US. Environmental Protection Agency
      (EPA) 40 Code of Federal Regulations (CFR) Part 1065 for on-road emission
      testing. Emissions of nitrogen oxides (NOx), carbon dioxide (CO2), and carbon
      monoxide (CO) were measured at load points specified by the International
      Organization for Standardization (ISO) to compare the two measurement methods.
      The average percentage errors calculated for PEMS measurements were 6.5%, 0.6%,
      and 357% for NOx, CO2, and CO, respectively. The NOx percentage error of 6.5%
      corresponds to a 0.22 to 1.11 g/kW-hr error in moving from Tier III (3.4 g/kW-hr)
      to Tier I (17.0 g/kW-hr) emission limits. Emission factors (EFs) of NOx and CO2
      measured via SMM were comparable to other studies and regulatory agencies
      estimates. However EF(PM2.5) for this study was up to 26% higher than that
      currently used by regulatory agencies. The PM2.5 was comprised predominantly of
      hydrated sulfate (70-95%), followed by organic carbon (11-14%), ash (6-11%), and
      elemental carbon (0.4-0.8%). IMPLICATIONS: This research provides direct
      comparison between the International Maritime Organization and U.S. Environmental
      Protection Agency reference methods for quantifying in-use emissions from ships.
      This research provides correlations for NOx, CO2, and CO measured by a PEMS unit
      (certified by U.S. EPA for on-road testing) against IMO's Simplified Measurement
      Method for on-board certification. It substantiates the measurements of NOx by
      PEMS and quantifies measurement error. This study also provides in-use modal and
      overall weighted emission factors of gaseous (NOx, CO, CO2, total hydrocarbons
      [THC], and SO2) and particulate pollutants from the main engine of a container
      ship, which are helpful in the development of emission inventory.

PMID- 23556239
TI  - The vanishing ozone weekday/weekend effect.
AB  - A national analysis of weekday/weekend ozone (O3) differences conducted using
      1997-1999 data found that many urban areas experienced at least 5% higher 8-hr
      maximum O3 concentrations on weekends than on weekdays even though emissions of
      precursors were significantly lower on weekends. This phenomenon was observed
      mostly in urban areas in the Northeast, Midwest, and coastal California. A
      similar analysis using 2008-2010 O3 data shows that this phenomenon has mostly
      vanished. From 1997-1999 to 2008-2010, the percentage of U.S. monitoring sites
      that experienced 95th percentile daily 8-hr maximum average O3 concentration on
      weekends that were 5% or more higher than on weekdays declined from about 35% to
      less than 5%. At the same time the percentage of sites that experienced higher
      weekday concentrations increased from 3% to about 27%. The majority (68%) of the
      sites, however exhibited little sensitivity to the weekday/weekend emission
      changes as they had similar (+/- 5%) O3 on weekdays and weekends. Similar trends
      were observed for the three other O3 metrics examined: the 95th percentile of the
      1-hr maximum and the April-September means of the 1-hr and 8-hr daily maxima.
      Over this time period, U.S. emissions of O3 precursors declined significantly.
      However, a greater decline in nitrogen oxides (NOx) emissions has caused an
      increase in the volatile organic compounds (VOC)/NOx emission ratios and it
      appears that this is the reason for the shift away from higher weekend O3
      concentrations. IMPLICATIONS: In areas where weekend emissions of ozone
      precursors are lower than on weekdays because of mainly lower motor vehicle
      emissions, an inadvertent test of ozone control strategies occurs. Such a test
      provides information on how control strategies that produce emission changes
      similar to those that occur on weekends affect ozone concentrations. In the late
      1990s, lower NOx emissions on weekends resulted in higher levels of ozone in many
      urban areas. Emission controls that have been enacted since then appear to have
      eliminated that phenomenon in most urban areas. However, most areas now indicate
      that weekend emission reductions now have little effect on ozone concentrations
      at most sites.

PMID- 23556240
TI  - A field trial of nutrient stimulation of methanotrophs to reduce greenhouse gas
      emissions from landfill cover soils.
AB  - Landfills are among the major sources of anthropogenic methane (CH4) estimated to
      reach 40 x 10(9) kg per year worldwide by 2015 (IPCC, 2007). A 2 1/2-year field
      experiment was conducted at a closed landfill in western Michigan where
      methanotrophs, methane-consuming bacteria, were stimulated by nutrient addition
      to the soil without significantly increasing biogenic nitrous oxide (N2O)
      production. The effects of the nitrogen amendments (KNO3 and NH4Cl),
      phenylacetylene (a selective inhibitor of nitrifying bacteria that contribute to
      N2O production), and a canopy (to reduce direct water infiltration) on the
      vertical soil gas profiles of CH4, CO2, and O2 were measured in the top meter of
      the soil. Methane and nitrous oxide fluxes were calculated from the corresponding
      soil gas concentration gradients with respect to depth and a Millington-Quirk
      diffusivity coefficient in soil derived empirically from soil porosity, water
      content, and diffusivity coefficients in air from the literature. Methane flux
      estimates were as high as 218.4 g m(-2) day(-1) in the fall and 12.8 g/m(-2) day(
      1) in the summer. During the spring and summer CH4 fluxes were reduced by more
      than half by adding KNO3 and NH4Cl into the soil as compared to control plots,
      while N2O fluxes increased substantially. The concurrent addition of
      phenylacetylene to the amendment decreased peak N2O production by half and the
      rate of peak methane oxidation by about one-third. The seasonal average methane
      and N2O flux data were extrapolated to estimate the reduction of CH4 and N2O
      fluxes into the atmosphere by nitrogen and inhibitor addition to the cover soils.
      The results suggest that such additions coupled with soil moisture management may
      provide a potential strategy to significantly reduce greenhouse gas emissions
      from landfills. IMPLICATIONS: The results of a 2 1/2-year study of effects of
      nutrient stimulation on methane oxidation in landfill cover soils demonstrates
      that nutrient addition does decrease methane emissions. The work further
      underscores the control which soil moisture exerts on methane oxidation. Water
      management is critical to the success of methane oxidation strategies.

PMID- 23556241
TI  - Temporal and spatial variation in recent vehicular emission inventories in China
      based on dynamic emission factors.
AB  - The vehicular emission trend in China was tracked for the recent period 2006-2009
      based on a database of dynamic emission factors of CO, nonmethane volatile
      organic compounds (NMVOC), NOx, PM10, CO2, CH4, and N2O for all categories of on
      road motor vehicles in China, which was developed at the provincial level using
      the COPERT 4 model, to account for the effects of rapid advances in engine
      technologies, implementation of improved emission standards, emission
      deterioration due to mileage, and fuel quality improvement. Results show that
      growth rates of CO and NMVOC emissions slowed down, but NOx and PM10 emissions
      continued rising rapidly for the period 2006-2009. Moreover CO2, CH4, and N2O
      emissions in 2009 almost doubled compared to those in 2005. Characteristics of
      recent spatial distribution of emissions and emission contributions by vehicle
      category revealed that priority of vehicular emission control should be put on
      the eastern and southeastern coastal provinces and northern regions, and
      passenger cars and motorcycles require stricter control for the reduction of CO
      and NMVOC emissions, while effective reduction of NOx and PM10 emissions can be
      achieved by better control of heavy-duty vehicles, buses and coaches, and
      passenger cars. Explicit provincial-level Monte Carlo uncertainty analysis, which
      quantified for the first time the Chinese vehicular emission uncertainties
      associated with both COPERT-derived and domestically measured emission factors by
      vehicle technology, showed that CO, NMVOC, and NOx emissions for the period 2006
      2009 were calculated with the least uncertainty, followed by PM10 and CO2,
      despite relatively larger uncertainties in N2O and CH4 emissions. The quantified
      low uncertainties of emissions revealed a necessity of applying vehicle
      technology- and vehicle age-specific dynamic emission factors for vehicular
      emission estimation, and these improved methodologies are applicable for routine
      update and forecast of China's on-road motor vehicle emissions. IMPLICATIONS:
      This paper tracks the temporal and spatial variation characteristics in recent
      vehicular emission inventories in China based on dynamic emission factors. The
      fact that CO and NMVOC emissions kept growing at reduced rates and the NOx, PM10,
      and GHG emissions continued rising rapidly reveals that it was insufficient to
      bring down the rapid growth of NOx, PM10, and CO2 emissions by merely tightening
      emission standards and improving fuel quality of motor vehicles. The results will
      assist decision makers to formulate effective control policies for China's
      vehicular emissions. The improved methodologies are applicable for routine update
      of China's vehicular emission inventories.

PMID- 23556242
TI  - Road versus roadside particle size distribution in a hot Mediterranean summer-
      estimation of fleet emission factors.
AB  - Particle size distribution at major on-road, roadside, and university-ground
      sites in Lebanon were studied in summer 2011. In a predominant old traffic fleet,
      it is shown that calculated PM2.5 mass emission factors (EFs) conform to those of
      heavy duty vehicles. When compared to roads in California, higher PM2.5 mass but
      similar particle number EFs are obtained for the average fleet of the on-road
      sites. This confirms the observed particle size distribution pattern, rich in
      particles in the accumulation range mainly between 0.425 and 0.675 microm with a
      prevalent peak at 0.475 microm. Corresponding total particle counts (TC) measured
      on the roadside are as high as 14,050 particles/cm3 and are up to 67% higher than
      particle counts measured at the university-ground site. In a hot, dry and humid
      summer weather with consistent temperature oscillations, particle dispersion is
      shown to be a function of meteorological factors, mainly the effect of the
      boundary-layer thickness, with particle counts measured during the morning being
      around 40% higher than particle counts measured during the afternoon.
      IMPLICATIONS: In a hot and humid Mediterranean summer, high emission factors are
      associated with an old car fleet. The observed diurnal variation in the particle
      count is attributed to the change in the thickness boundary layer in summer. In
      comparison to road sites, the particle size distribution shows the prevalence of
      larger size particles. Particle counts measured at the roadside sites are at
      least 20% higher than those of the road sites. The findings call for the
      reinforcement of local regulations on car age. Furthermore, the high number of
      particles can cause or aggravate a number of health and ecosystem problems.

PMID- 23556243
TI  - Estimating air chemical emissions from research activities using stack
      measurement data.
AB  - Current methods of estimating air emissions from research and development (R&D)
      activities use a wide range of release fractions or emission factors with bases
      ranging from empirical to semi-empirical. Although considered conservative, the
      uncertainties and confidence levels of the existing methods have not been
      reported. Chemical emissions were estimated from sampling data taken from four
      research facilities over 10 years. The approach was to use a Monte Carlo
      technique to create distributions of annual emission estimates for target
      compounds detected in source test samples. Distributions were created for each
      year and building sampled for compounds with sufficient detection frequency to
      qualify for the analysis. The results using the Monte Carlo technique without
      applying a filter to remove negative emission values showed almost all
      distributions spanning zero, and 40% of the distributions having a negative mean.
      This indicates that emissions are so low as to be indistinguishable from building
      background. Application of a filter to allow only positive values in the
      distribution provided a more realistic value for emissions and increased the
      distribution mean by an average of 16%. Release fractions were calculated by
      dividing the emission estimates by a building chemical inventory quantity. Two
      variations were used for this quantity: chemical usage, and chemical usage plus
      one-half standing inventory. Filters were applied so that only release fraction
      values from zero to one were included in the resulting distributions. Release
      fractions had a wide range among chemicals and among data sets for different
      buildings and/or years for a given chemical. Regressions of release fractions to
      molecular weight and vapor pressure showed weak correlations. Similarly,
      regressions of mean emissions to chemical usage, chemical inventory, molecular
      weight, and vapor pressure also gave weak correlations. These results highlight
      the difficulties in estimating emissions from R&D facilities using chemical
      inventory data. IMPLICATIONS: Air emissions from research operations are
      difficult to estimate because of the changing nature of research processes and
      the small quantity and wide variety of chemicals used. Analysis of stack
      measurements taken over multiple facilities and a 10-year period using a Monte
      Carlo technique provided a method to quantify the low emissions and to estimate
      release fractions based on chemical inventories. The variation in release
      fractions did not correlate well with factors investigated, confirming the
      complexities in estimating R&D emissions.

PMID- 23556244
TI  - Integrated waste management in batch chemical industry based on multi-objective
      optimization.
AB  - A multi-objective optimization methodology for hazardous liquid waste management
      is presented in this paper using industrially based LCA models and operating
      constraints. This approach is used to optimize the handling of waste streams
      introducing flexible mixing policy scenarios compared to the rigid policy
      scenarios of the industrial system. It is shown that increasing the degrees of
      freedom for the waste mixing reduces significantly both the operating cost and
      the environmental impact by avoiding the use of utilities. Moreover, the
      influence of waste availability as function of production planning without waste
      storage is analyzed in several multiperiod optimizations. There, it is
      demonstrated that this saving potential can be further increased by integration
      of multiperiod production planning with waste management policies, up to the
      level of 40% for the environmental impact, and more than 50% for the operating
      cost, compared to the industrial base case. In some specific cases, a proper
      matching of production planning and waste mixing policies can also turn the waste
      treatment into a source of profit exploiting energy production from the
      incineration process. IMPLICATIONS: This study reveals the savings potential of
      more flexible policies in waste management, in particular waste mixing of liquid
      waste in batch chemical industries treated in incineration, wet air oxidation,
      wastewater treatment plants, or recovered by distillation. Through a multi
      objective optimization framework including models for operating costs and life
      cycle inventories based on industrial data, operating constraints from industrial
      practice, and terminal constraints from legislation, savings potentials up to 50%
      for the operation cost and 40% for the environmental impact are demonstrated in
      two case studies.

PMID- 23556245
TI  - An algorithm to estimate aircraft cruise black carbon emissions for use in
      developing a cruise emissions inventory.
AB  - To provide accurate input parameters to the large-scale global climate simulation
      models, an algorithm was developed to estimate the black carbon (BC) mass
      emission index for engines in the commercial fleet at cruise. Using a high
      dimensional model representation (HDMR) global sensitivity analysis, relevant
      engine specification/operation parameters were ranked, and the most important
      parameters were selected. Simple algebraic formulas were then constructed based
      on those important parameters. The algorithm takes the cruise power
      (alternatively, fuel flow rate), altitude, and Mach number as inputs, and
      calculates BC emission index for a given engine/airframe combination using the
      engine property parameters, such as the smoke number, available in the
      International Civil Aviation Organization (ICAO) engine certification databank.
      The algorithm can be interfaced with state-of-the-art aircraft emissions
      inventory development tools, and will greatly improve the global climate
      simulations that currently use a single fleet average value for all airplanes.
      IMPLICATIONS: An algorithm to estimate the cruise condition black carbon emission
      index for commercial aircraft engines was developed. Using the ICAO certification
      data, the algorithm can evaluate the black carbon emission at given cruise
      altitude and speed.

PMID- 23556246
TI  - Providers try to keep bearings in tech fog.

PMID- 23556247
TI  - 20 to watch. Part 3: Stars in their own right.

PMID- 23556248
TI  - Oral health basics.

PMID- 23556249
TI  - Paying for dental work in long term care.

PMID- 23556250
TI  - Long term care software suppliers guide 2013.

PMID- 23556251
TI  - Hot weather and safety eyewear: a closer look at the hazards.

PMID- 23556252
TI  - Walking the path to effective controls.

PMID- 23556253
TI  - Four steps to protection.

PMID- 23556254
TI  - Staying on top of the problem.

PMID- 23556255
TI  - Is your organization bullying-proof?

PMID- 23556256
TI  - NFPA 654 2013 edition revised requirements for housekeeping.

PMID- 23556257
TI  - Integrated safety system technology is here.

PMID- 23556258
TI  - Stop trying to create a safety culture.

PMID- 23556259
TI  - Cervical human papillomavirus infection in a sample of Hispanic women living in
      Puerto Rico: comparison with cervical cytology reports.
AB  - OBJECTIVE: Persistent infection with high-risk (HR) HPV is a necessary risk
      factor for the development of cervical cancer. Information on HPV infection is
      limited in Puerto Rico. This study determined the distribution of HPV types and
      the association of HR-HPV types with cervical pathology in a clinic-based sample
      of women in PR. METHODS: Data from 92 female participants aged 18 to 34 years and
      recruited from the University of Puerto Rico-Gynecology Clinic, were analyzed.
      Cervical cytology was performed. HPV testing was performed using L1 consensus
      primer PCR with MY09/ MY11 primers and typed by dot-blot hybridization. Logistic
      regression modeling was used to determine the crude and covariate adjusted
      association between HR-HPV and cervical pathology. RESULTS: Twenty percent (n =
      18) of the patients had abnormal cytology, 45.7% (n = 42) were HPV positive, and
      30.4% (n = 28) were HR HPV-positive. Women infected with HR-risk HPV types were
      7.9 (95% CI = 2.5-25.5) times more likely to have abnormal cytology as compared
      to women without HR infection when adjusted by age and age at first sexual
      intercourse. CONCLUSION: The burden of HPV infection was high, and, as expected,
      HR HPVs were strongly associated with dysplasia. A population-based study is
      needed to estimate HPV prevalence and its association with related malignancies
      in our population. This will be of great value in determining disease burden and
      will increase awareness of the HPV vaccination in our population.

PMID- 23556261
TI  - Heart tumors in Puerto Rico de novo atrial fibrillation as clinical presentation
      in a subgroup of patients.
AB  - OBJECTIVE: Primary cardiac tumors are rare neoplasms in humans, of which the most
      common is the atrial Myxoma. The objective of this study was to find the
      incidence of these tumors at the Heart Center of Puerto Rico and the Caribbean.
      METHODS: This study was approved by the Institutional Review Board of the Medical
      Sciences Campus University of Puerto Rico to review the records at the Heart
      Center of patients with heart tumors in the last 14 years. RESULTS: The sample
      consists of 55 patients (78.9% were females and 24.1% were male) with a median
      age of 52 years. Sixty-five percent of patients lived in rural areas. Clinical
      presentations included shortness of breath (43.1%), chest pain (37.9%),
      asymptomatic (25%), palpitations (20.7%), neurologic symptoms (10.3%) and
      dizziness (6.9%). Electrocardiographic findings included normal sinus rhythm
      (53.4%), non-specific ST-T changes (32.8%), sinus tachycardia (20.7%), left
      atrial enlargement (10.3%) and atrial fibrillation (8.6%). A subgroup presenting
      with atrial fibrillation prior to diagnosis had left atrial myxoma. The tumors
      found, in descending order of frequency are: left atrial myxoma, right atrial
      myxoma, papillary fibroelastoma, hamartoma, lipoma and rhabdomyoma. We found a
      correlation between large left atrial myxoma and atrial fibrillation. CONCLUSION:
      The most frequent heart tumor was atrial myxoma. The larger myxomas were
      associated with atrial fibrillation.

PMID- 23556260
TI  - HIV and syphilis infection among men attending a [corrected] sexually transmitted
      infection clinic in Puerto Rico.
AB  - OBJECTIVE: This study aimed to assess the demographic, behavioral, and clinical
      factors associated with HIV and syphilis infection among a sample of men
      attending a sexually transmitted infection clinic during 2009 to 2010 in San
      Juan, Puerto Rico (PR). METHODS: A sample of 350 clinical records from men
      visiting the clinic for the first time during 2009 to 2010 was reviewed.
      Descriptive statistics were used to describe the study sample, and bivariate
      analyses were performed separately for HIV and syphilis to identify factors
      associated with these infectious diseases. Variables that were significantly
      associated (p < 0.05) with HIV and syphilis in the bivariate analysis were
      considered for inclusion in the logistic regression models. RESULTS: Overall,
      11.2% and 14.1% of the men were infected with HIV and syphilis, respectively, and
      5.1% were coinfected with HIV and syphilis. In multivariate logistic regression
      models, ever injecting drugs (POR = 8.1; 95% CI 3.0, 21.8) and being a man who
      has sex with men (MSM) (POR = 5.3; 95% CI 2.3, 11.9) were positively associated
      with HIV infection. Being a man older than 45 years (POR = 4.0; 95% CI: 1.9, 8.9)
      and being an MSM (POR = 2.5; 95% CI: 1.3, 4.9) were both significantly associated
      with syphilis infection. CONCLUSION: These findings reinforce the need for
      greater education and prevention efforts for HIV and other STIs among men in PR,
      particularly those who are MSM. However, there is a need to make an a priori
      assessment of the level of health literacy in the members of this group so that a
      culturally sensitive intervention can be provided to the men who attend this STI
      clinic.

PMID- 23556262
TI  - Pediatric dentistry workforce in Puerto Rico: results of a 2011 survey.
AB  - OBJECTIVE: Determine the socio-demographic and educational characteristics of and
      develop a profile of practice for Pediatric Dentists (PDs) in Puerto Rico.
      METHODS: A 34-item questionnaire assessing 3 dimensions: socio-demographic and
      education, practice profile, and level of satisfaction/desire to relocate, was
      developed and pre-tested for comprehensiveness, validity, and reliability. Data
      were collected through telephone interviews by a calibrated interviewer, entered
      and tabulated using Excel (Microsoft Office 2010) and exported to SPSS v. 17
      (SPSS Inc., Chicago, IL). Descriptive statistical analyses were conducted.
      RESULTS: Eighty percent (80%) of all of the licensed PDs in PR participated in
      our study. The typical PD in PR has been in practice for 19 years, is 48 years
      old, and spends 31 hours/week providing clinical care. Female PDs, who comprise
      70% of the PD workforce, devote more time to clinical and managerial activities
      than do their male counterparts. Seventy-three percent (73%) of the current PD
      workforce will be retiring within the next 20 years and 70% are solo
      practitioners. Most PDs (65%) participate in the government-subsidized dental
      insurance program "Mi Salud," which represents as much as 48% of their income.
      PDs beginning or ending their careers were more likely to be participating
      providers for "Mi Salud" than were those in mid-career. CONCLUSION: In evaluating
      the adequacy of the pediatric dentistry workforce in Puerto Rico, the socio
      demographic information of the PDs and the characteristics of their practices
      must be taken into account. These variables must be examined in relation to
      epidemiological indicators as well as environmental factors, including the
      comprehensiveness of dental benefits and the adequacy of reimbursement levels by
      third-party payers, which when inadequate may lead to decreased access to care.

PMID- 23556263
TI  - Assessment of the national school lunch program in a subset of schools in San
      Juan, Puerto Rico: participants vs. non-participants.
AB  - OBJECTIVE: Extensive evaluations of the national school lunch program (NSLP) have
      been carried out on the U.S. mainland. Puerto Rico, a commonwealth of the U.S. is
      a participant in this program, but has never been included in assessment studies.
      Herein, we present assessment information and compare results with comparable
      mainland studies. METHODS: Multiple 24-hr recall questionnaires were administered
      to groups of participating (P) and non-participating (NP) children in the lunch
      program at 3 educational levels. Comparisons were made for children within the
      study as well as between comparable children in mainland studies for total intake
      of several macro- and micro-nutrients, contribution of the lunch to the total
      daily intake and adherence to U.S. Recommended Dietary Allowances (RDA's) or to
      Dietary Reference Intakes (DRI's) including acceptable macronutrient distribution
      ranges (AMDR's). RESULTS: Target intakes were met by P for % of the RDA of energy
      from protein, for all water soluble vitamins, iron, zinc and cholesterol. P did
      not achieve target intakes for total energy, energy from carbohydrates and fat
      nor for fat soluble vitamins, calcium, magnesium, phosphorus, potassium and
      fiber. Recommended levels were exceeded for sodium, total fat and saturated fat.
      Comparing P vs NP, the vast majority of both groups fell within AMDR
      recommendations for macronutrients but not all micronutrients. CONCLUSION: For
      the most part, our results parallel those obtained in the National sample
      however, results suggest that P in the lunch program in Puerto Rico have a
      healthier intake of several nutrients than NP students. The unique feature of
      this study is that it is the first assessment of the NSLP in a completely
      Hispanic population.

PMID- 23556264
TI  - Dietary patterns and their association with sociodemographic characteristics and
      perceived academic stress of college students in Puerto Rico.
AB  - OBJECTIVE: University students face academic responsibilities that may produce
      stress, which may lead to changes in dietary patterns (DPs). These changed
      patterns can become dysfunctional, often resulting in a negative impact on the
      health of the stressed student. Little is known about DPs in college students in
      Puerto Rico (PR). The purpose of this study was to describe the DPs of college
      students in PR and the association of these patterns with socio-demographic
      characteristics and perceived academic stress. METHODS: This retrospective
      epidemiological study investigated self-reported DPs in a representative sample
      of 275 college students, in relation to socio-demographic characteristics, body
      composition (BC), and perceived academic stress; a Diet Quality Index was
      developed using the USDA Food Patterns for 2010 to determine whether their DPs
      were adequate or inadequate. RESULTS: Most of the participating students were
      female (67.6%), ranged from 21 to 30 years old (88%), lived in low household
      incomes (42.7%), and had healthy weights (56.4%). Most of the students perceived
      the stress levels as being moderate (60.7%). Most had diets that were below the
      dietary recommendations for grains, fruits, vegetables, dairy products, and
      protein, whereas fat consumption was adequate. Overall, most had inadequate DPs
      (62%). DP was significantly associated with age (p < 0.05); older students had
      better DPs than did younger students. In terms of the different schools (p <
      0.05), those students from the School of Medicine and those from the School of
      Public Health had better DPs than did the students from the other schools. DP was
      not associated with income, gender, BMI, stress level, or course load.
      CONCLUSION: The majority of the students had inadequate DPs, which inadequacy was
      associated with both the age of the student and the school that he or she
      attended.

PMID- 23556265
TI  - Physical activity and its associations with sociodemographic characteristics,
      dietary patterns, and perceived academic stress in students attending college in
      Puerto Rico.
AB  - OBJECTIVE: The academic environment usually generates stress in students.
      Increasing physical activity (PA) is one of the stress-coping strategies for
      students; however, students usually reduce their PA while enrolled in college.
      OBJECTIVE: To determine the association between PA, self-perceived academic load
      and stress, and dietary patterns in students attending college in Puerto Rico.
      METHODS: A proportional stratified sample of 275 students from UPR-MSC completed
      a self-administered questionnaire on socioeconomic status, academic load and
      stress, body composition, dietary patterns, and PA. Chi2 was used to assess the
      association between variables. RESULTS: Most of the participants were female
      (68%), were aged 21 to 30 years (88%), and had low annual household incomes ($0
      $24,999) (43%). Women reported higher levels of stress (p < 0.001) than did men.
      Overweight and obesity was found in 35.4%, while most students reported a light
      PA level (46.5%), which was higher among women (p < 0.001). During periods of
      greater stress, most students increased sedentary activities (68%), and -30%
      reported a decrease in moderate and vigorous activities; however, 60% reported
      that PA was an effective coping strategy and 66% would use it again. There was a
      negative association between PA and stress: those with higher levels of stress
      had lower PA levels (p = 0.06). No significant associations were found between PA
      and the others variables studied (p > 0.05). CONCLUSION: Most students reported
      sedentary lifestyles during periods of greater stress. High level of stress were
      positively associated with a light PA level.

PMID- 23556267
TI  - UDM, U-M dental school deans respond to 'change' editorial.

PMID- 23556266
TI  - Small cell neuroendocrine carcinoma of rectum with associated paraneoplastic
      syndrome: a case report.
AB  - Neuroendocrine carcinomas of the colon and rectum comprise fewer than 1% of all
      colorectal cancers. These aggressive tumors generally have a poor prognosis
      compared to that associated with colorectal adenocarcinoma. We describe herein
      the case of a 68-year-old female presenting with a bleeding rectal mass involving
      the anal canal, which case was associated with hyponatremia due to inappropriate
      serum levels of antidiuretic hormone. The histopathological examination was
      consistent with a small-cell neuroendocrine tumor. She was treated with
      combination chemotherapy and radiation therapy. The Syndrome of Inappropriate
      Antidiuretic Hormone (SIADH) was managed with vasopressin antagonists. After the
      completion of therapy, endoscopic ultrasound revealed evidence of residual
      disease, for which she underwent an abdominoperineal resection (APR). The patient
      died 4 months later of disease progression. To our knowledge, this is the first
      report of a small-cell neuroendocrine tumor involving the rectum and anal canal
      that presented with the paraneoplastic syndrome, SIADH.

PMID- 23556268
TI  - The new AAOS/ADA clinical practice guidelines for management of patients with
      prosthetic joint replacements.

PMID- 23556269
TI  - Do not ignore antitrust law! Important information for all dentists.

PMID- 23556270
TI  - The ABCs of paid time off.

PMID- 23556271
TI  - What are our ethical responsibilities on the Web?

PMID- 23556272
TI  - There oughta be a code for that!

PMID- 23556273
TI  - Listening: every second counts.

PMID- 23556274
TI  - Achieving better esthetics by gingival de-pigmentation: report of three cases
      with a review of the literature.
AB  - A smile expresses a feeling of joy and success and also reveals self-confidence
      and kindness in an individual. A holistic smile is dictated not only by the
      shape, position and color of the teeth but also by the health of the gingival
      tissues. Gingival appearance is an important component of an attractive smile.
      Melonin, carotene and hemoglobin are the most common natural pigments
      contributing to the normal color of gingiva. Although physiologic and ethnic
      melanin pigmentation is not a medical problem, complaints about "black gums" are
      common. For de-pigmentation of gingiva, different treatment modalities have been
      reported such as bur abrasion, scraping with scalpel, partial thickness flap,
      gingivectomy, cryotherapy, electrosurgery, lasers, free gingival autografting,
      sub-epithelial connective tissue graft and combination techniques. In the present
      case reports, scalpel surgery and electrosurgery were performed for gingival de
      pigmentation, which are simple and effective. The esthetic results were pleasing
      and healing was uneventful. Patients were satisfied with the outcome at three
      month follow-up as evidenced from their feedback.

PMID- 23556275
TI  - The B-24 liberator and Dr. Bill Godwin.

PMID- 23556276
TI  - Potential effects of the Afford Care Act on dentistry.
AB  - The Affordable Care Act (ACA) has the potential to reshape health care in
      America. The expansion of medical insurance coverage, a move toward more
      integrated care delivery, and significant changes to how health care is financed
      are some of the main changes expected. Several aspects of the ACA have important
      implications for dentists as oral health care professionals and small business
      employers, as well as consumers of medical care. While much of the effect of the
      ACA on health care in general and on dentistry in particular remains uncertain at
      this stage, it is important to highlight some of the potential changes that are
      likely to occur.

PMID- 23556278
TI  - Diagnosing a computer--Part 2.

PMID- 23556277
TI  - The DentalEar.

PMID- 23556279
TI  - The four steps for "done right" accountability.

PMID- 23556280
TI  - Follow a post-exposure plan after needlestick injury.

PMID- 23556281
TI  - What is the bloodborne pathogens standard?

PMID- 23556282
TI  - Dr. Wesley Sato: young dentist gets involved. Interview by Dr. Bill Scheerer.

PMID- 23556283
TI  - Fine-tuning our strategies to strengthen our future.

PMID- 23556284
TI  - Patient choice--is more always better?

PMID- 23556285
TI  - Your resource and advocate--one phone call away.

PMID- 23556286
TI  - The golden age of dentistry?

PMID- 23556287
TI  - Oral Pathology Quiz #78. Case number 1. Benign hyperkeratosis.

PMID- 23556288
TI  - Oral Pathology Quiz #78. Case number 2. Pyogenic granuloma.

PMID- 23556289
TI  - Oral Pathology Quiz #78. Case number 3. Lateral dental granuloma.

PMID- 23556290
TI  - Oral Pathology Quiz #78. Case number 4. Florid cemento-osseous dysplasia.

PMID- 23556291
TI  - I went to Everest and found an angel.

PMID- 23556292
TI  - Planning the shade prescription.

PMID- 23556293
TI  - Making treatment more accessible.

PMID- 23556294
TI  - New antiplatelet and anticoagulant drugs. Considerations for dental patient
      management.
AB  - A recent occurrence in dental practice is the noting of new "blood thinners" when
      the clinician is reviewing a patient's medical history and medications. "Doc, I
      take Pradaxa or Effient or Xarelto" etc. After many years of the widespread use
      of aspirin and Coumadin there has appeared a new generation of medications
      focused on reducing thromboembolic events in patients at risk. This trend has
      been driven by a need for drugs providing better drug efficacy based on patient
      biologic processing of the medications and the frequency and cost factors
      associated with the monitoring the degree of anticoagulation. Guidelines for
      assessing bleeding risk and managing patients on these new medications in dental
      practice are not yet defined and are empirically based on medical practitioner
      experience. This paper will review these new medications and will discuss current
      considerations for dental patient care. (Note that not all new antiplatelet and
      anticoagulant medications will be reviewed in this paper.)

PMID- 23556295
TI  - It's Mr Hunt who is missing the point.

PMID- 23556296
TI  - Nurses could be asked to buy extra holiday by south west consortium.

PMID- 23556298
TI  - Reported incidences of attacks and bullying at work almost double.

PMID- 23556297
TI  - Performance-related pay to be rolled out across English NHS.

PMID- 23556299
TI  - Suspend NHS services that fail to meet basic standards--Francis.

PMID- 23556300
TI  - Paying the price for the errors of others.

PMID- 23556301
TI  - Struggle to be heard in the new health service.
AB  - On April 1, major NHS reform in England will see the introduction of a system
      that puts NHS spending in the hands of clinicians. This article, the first in a
      series, outlines the new commissioning organisations and details the progress
      made in Cumbria, where nurses play a leading role on the clinical commissioning
      group.

PMID- 23556302
TI  - Stop the bullies.
AB  - This article offers guidance on how to speak out if you are the victim of
      bullying or harassment, or you see a colleague being abused. The problem is
      widespread, with one in seven respondents to the 2011 NHS staff survey saying
      they had experienced bullying, harassment or abuse.

PMID- 23556303
TI  - Food as treatment.
AB  - Nutrition has not always been a priority for nurses and doctors. Consequently, 70
      per cent of patients lose weight while in hospital, and malnutrition leads to
      longer stays and readmission. However, recent initiatives are placing the focus
      firmly on good nutritional care.

PMID- 23556304
TI  - Lowering risk of CMV.
AB  - Teenager Alicia Parks' severe disabilities are the result of being born with
      congenital cytomegalovirus (CMV). Alicia's mother, paediatric nurse Mandy Parks,
      is calling for greater awareness of CMV among nurses. She explains the simple
      precautions that can reduce the spread of this common infection.

PMID- 23556305
TI  - Use of dabigatran to prevent stroke in patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) is a major risk factor for ischaemic stroke.
      Anticoagulant therapy, such as warfarin, is prescribed to prevent stroke in
      patients with AF. Careful monitoring is required to achieve safe and effective
      levels of warfarin in the blood. In March 2012, the National Institute for Health
      and Clinical Excellence recommended a new anticoagulant--dabigatran etexilate-
      for the prevention of stroke in patients with AF. Treatment with dabigatran
      requires less monitoring than warfarin and may therefore enhance the care of this
      patient group. However, it is important to note that some patients may be at
      increased risk of serious side effects associated with dabigatran. This article
      discusses the risks and benefits of using dabigatran for stroke prevention in
      patients with AF.

PMID- 23556306
TI  - Establishing a domestic abuse care pathway: guidance for practice.
AB  - Domestic abuse is an increasing public health concern, and the relationship
      between such abuse and poor health is now recognised. Guidance produced in 2012
      by Co-ordinated Action Against Domestic Abuse, the Identification and Referral to
      Improve Safety programme, and the Royal College of General Practitioners
      encourages general practices to establish a domestic abuse care pathway, so that
      the correct processes for identifying and responding to domestic abuse are
      followed. A care pathway is necessary because there is evidence that healthcare
      professionals' responses to domestic abuse are not always helpful. This guidance
      has the potential to improve the way that healthcare professionals in primary
      care respond to domestic abuse. While supporting the guidance, suggestions are
      made for nurses to develop the care pathway further.

PMID- 23556307
TI  - Assessment and management of patients with diabetic foot ulcers.
AB  - Diabetic neuropathy is a common complication of diabetes. Patients need to be
      informed of the effects of poorly managed diabetes and appropriate care to
      prevent diabetic neuropathy. This article provides a brief overview of the main
      complications associated with diabetes and discusses the different types of
      diabetic neuropathy. Risk factors in the development of diabetic foot ulcers are
      identified and the importance of timely assessment is recognised. Treatment and
      management of diabetic foot ulcers is discussed in relation to blood glucose
      control, infection, wound care, sleep and pain.

PMID- 23556308
TI  - Surgical patients with diabetes.

PMID- 23556310
TI  - Speaking openly via mediation.

PMID- 23556309
TI  - A taste of practice.

PMID- 23556311
TI  - Teaching dignity in five steps.

PMID- 23556312
TI  - Who needs sleep?

PMID- 23556313
TI  - Mandated dental screening: what state governments consider.

PMID- 23556314
TI  - Members making a difference: Chester Grace Dental Clinic.

PMID- 23556315
TI  - The proportion of elderly in Pennsylvania is slipping but....
AB  - Media reports describing the anticipated increase of tens of millions of elderly
      residents and their attendant billions of dollar costs for health services during
      the next decades are difficult for any person to place in proper perspective. As
      a result, these estimates become "just numbers" not actual people. Census Bureau
      reports are used at the national, state and county levels to provide an increased
      meaningful picture when the 65 and older population of Pennsylvania will increase
      to 22.6 percent of the state population. In 2000, 12.4 percent of the U.S.
      population was 65 years and older (15.6 percent in Pennsylvania, 1.9 million
      elderly). Only in the state of Florida was the proportion greater. In 2010, the
      proportion of elderly in the population of Pennsylvania ranked 4th (behind
      Florida, West Virginia and Maine). It was tied for 3rd (behind Florida and North
      Dakota) with 2.5 percent of the population 85 years and over. By 2030, the
      projected number of elderly in Pennsylvania (22.6 percent of the state
      population) will rank 11th. But ... "Starting on Jan 1, (2011) our 79-million
      strong baby boomer generation will be turning 65 at the rate of one elderly every
      eight seconds.

PMID- 23556317
TI  - Chemical constituents of bryophytes. Bio- and chemical diversity, biological
      activity, and chemosystematics.

PMID- 23556316
TI  - Asymmetric organocatalysis in natural product syntheses.

PMID- 23556318
TI  - "Rules of Six"--diagnostic and therapeutic guidelines for single-tooth implant
      success.
AB  - Replacing a single anterior tooth with an implant requires meeting a number of
      interdependent challenges, including biologic, functional, and esthetic features
      of success. The principles of osseointegration, the fundamentals of esthetics,
      and concerns regarding occlusion and function are elements that need to be
      addressed to achieve implant-supported crown success. In this report, the "Rules
      of Six" for effectively placing a single-tooth dental implant are described.
      These rules represent diagnostic targets and a single therapeutic guideline
      useful in directing clinical success and preventing common complications.

PMID- 23556319
TI  - Establishing a classification system and criteria for veneer preparations.
AB  - The concept of no- or minimal-preparation veneers is more than 25 years old, yet
      there is no classification system categorizing the extent of preparation for
      different veneer treatments. The lack of veneer preparation classifications
      creates misunderstanding and miscommunication with patients and within the dental
      profession. Such a system could be indicated in various clinical scenarios and
      would benefit dentists and patients, providing a guide for conservatively
      preparing and placing veneers. A classification system is proposed to divide
      preparation and veneering into reduction--referred to as space requirement,
      working thickness, or material room--volume of enamel remaining, and percentage
      of dentin exposed. Using this type of metric provides an accurate measurement
      system to quantify tooth structure removal, with preferably no reduction, on a
      case-by-case basis, dissolve uncertainty, and aid with multiple aspects of
      treatment planning and communication.

PMID- 23556321
TI  - Accelerated esthetic dental results using an interdisciplinary approach.
AB  - Traditionally, achieving case acceptance in situations that involve orthodontics
      has been challenging for clinicians, especially among adult male patients. In
      recent years, surgically accelerated orthodontics has emerged as an alternative
      approach for patients who might otherwise avoid treatment or choose a compromised
      form of treatment due to esthetic concerns about wearing traditional braces. In
      this case report, use of an interdisciplinary approach that combined Kois
      diagnostic principles with Accelerated Osteogenic Orthodontics (AOO) and lingual
      braces resulted in a successful restoration while maintaining satisfactory
      esthetics during treatment.

PMID- 23556320
TI  - Controlling the periodontal-restorative interface to provide esthetic dentistry
      for an esthetically high-risk patient.
AB  - This case involved a young female patient with anterior wear and a high lip line
      and thin tissue biotype. An organized approach was carried out to diagnose the
      esthetic problems so that a multidisciplinary treatment plan could be devised.
      The comprehensive plan included occlusal analysis and equilibration to establish
      maximum intercuspation in harmony with centric relation, correction of gingival
      levels, feldspathic porcelain restorations, and teeth bleaching. The case
      demonstrates technological advances and improvement in dentistry's understanding
      of the science of color and dental ceramics.

PMID- 23556322
TI  - Mercury from dental amalgam: exposure and risk assessment.
AB  - There has long been an undercurrent within the dental profession of anti-amalgam
      sentiment, a "mercury-free" movement. To assess whether anything is or is not
      scientifically wrong with amalgam, one must look to the vast literature on
      exposure, toxicology, and risk assessment of mercury. The subject of risk
      assessment goes straight to the heart of the debate over whether a malgam is
      safe, or not, for unrestricted use in dentistry in the population at large.

PMID- 23556323
TI  - Preparing patients for future oral healthcare decline: what dentists can do
      today.

PMID- 23556324
TI  - DenMat's Snap-on Smile offers convenient solution for geriatric patients.

PMID- 23556325
TI  - Help for would-be or struggling authors.

PMID- 23556326
TI  - Can you touch your toes? Using tables of evidence (TOES) to organize your
      evidence review.

PMID- 23556327
TI  - Elaboration of leadership and culture in high-performing nursing units of
      hospitals as perceived by staff nurses.
AB  - The leadership-culture phenomenon, a known explanatory construct for
      organizational performance, is understudied in nursing. Building on our previous
      work, we further addressed this knowledge gap through explorations of
      demographics and hospital variables which may have a significant influence on
      staff nurses' (SNs) perceptions of their nurse managers' (NMs) leadership and
      nursing unit culture. Furthermore, we explored the extent to which the NMs'
      leadership predicted specific cultures which typify nursing unit effectiveness.
      Using dissertation data provided by278 SNs, we found that SNs educated at the
      baccalaureate level or higher had favorable perceptions of their nursing unit
      performance and viewed their NMs' leadership differently than the SNs with
      diploma or associate degrees. The frequent portrayals of transformational (TFL)
      leadership behaviors (e.g., visionary) by the NMs were paramount in shaping
      culture traits which exemplify high performance outcomes. TFL leaders were more
      likely to shape unit cultures which are flexible and adaptive to the
      environmental challenges within and outside the nursing unit. Thus, the type of
      NMs' leadership and unit culture may provide an added value in explaining the
      performance level in patient care units which consequently affects the overall
      hospital/organizational outcomes. Implications for research and leadership
      practices are presented.

PMID- 23556328
TI  - Doctor shopping: a concept analysis.
AB  - Prescription drug abuse is a significant problem in the United States that poses
      a serious health risk to Americans and is therefore significant to the field of
      nursing. The prescription drugs that are designated in the United States as
      having abuse potential are called controlled or scheduled drugs. The most common
      types of abused prescription drugs are benzodiazepines prescribed for anxiety,
      opioids prescribed for pain, and stimulants prescribed for attention deficit
      disorder. These prescription drugs are abused by taking larger doses than
      prescribed for nonmedical use to achieve a high or euphoric feeling, or are sold
      illicitly for profit. In 2009, there were 2.4 million nonmedical users of
      prescription opioids in the United States. These prescription drugs are often
      obtained by seeing multiple prescribers, often under false pretenses or with
      complicity from the prescribers that leads to abuse and illicit sales. The term
      doctor shopping has been used not only to refer to this phenomenon but has also
      had other meanings throughout the past decades. Thus, concept analysis is the
      focus of this article for clarification using the Walker and Avant method. Health
      implications and suggestions for minimizing doctor shopping are included.

PMID- 23556329
TI  - An interdisciplinary approach to research management in anesthesia: the
      integrated clinical research team model.
AB  - The Anesthesia Clinical Research Unit (ACRU) at Boston Children's Hospital
      developed the integrated clinical research team model in 2009 as a framework to
      support the high ethical standards and team-based approach in pediatric
      anesthesia research which was already established within the department. The
      foundation of the model is built on interdisciplinary collaboration,
      communication, and integrity in the field of clinical research. Above all, the
      work of the ACRU is focused on the patients, families and community as a whole.
      In order to uphold these standards, each member of the ACRU has a clearly-defined
      role while still promoting the core fundamentals of teamwork and continuity of
      care. This department-wide, team-based approach to clinical research has proven
      to be effective in its resourcefulness and productivity in running numerous large
      projects concurrently within the department.

PMID- 23556330
TI  - Nonverbal communication behaviors of internationally educated nurses and patient
      care.
AB  - BACKGROUND: Because of language barriers and cultural differences,
      internationally educated nurses (IENs) face documented communication challenges
      in health care delivery. Yet, it is unknown how and to what extent nonverbal
      behaviors affect patient care because of research gap in the existing nursing
      literature. METHODS: This is an exploratory study evaluating nonverbal
      communication behaviors of IENs interacting with standardized patients (SPs) in a
      controlled clinical setting through videotape analysis. Participants included 52
      IENs from two community hospitals in the same hospital system in a southwestern
      metropolitan area in the United States. Twelve nonverbal behaviors were rated
      using a 4-point Likert scale with 4 indicating the best performance by the
      research team after watching videos of SP-IEN interactions. The global
      communication performance was also ranked in four areas: genuineness,
      spontaneity, appropriateness, and effectiveness. The relationships between these
      four areas and the nonverbal behaviors were explored. Finally, a qualitative
      analysis of two extreme cases was conducted and supplemented the quantitative
      findings. RESULTS: The IENs received average scores under 2 in 5 out of the 12
      nonverbal behaviors. They were "hugging" (1.06), "lowering body position to
      patient's level" (1.07), "leaning forward" (1.26), "shaking hands" (1.64), and
      "therapeutic touch" (1.66). The top three scores were for "no distractive
      movement," "eye contact," and "smile" (3.80, 3.73, and 3.57, respectively). The
      average overall global impression score was 2.98. The average score for
      spontaneity was 2.80, which was significantly lower than the scores for
      genuineness (3.15), appropriateness (3.11), but comparable to the average score
      for effectiveness (2.85). Finally, therapeutic touch, interpersonal space, eye
      contact, smiling, and hugging were all significantly correlated with one or more
      of the global impression scores, with therapeutic touch showing moderate
      correlations with all of the scores as well as the overall global impression
      score. IMPLICATIONS: The IENs' nonverbal behaviors in areas such as hugging,
      lowering body position to patient's level, leaning forward, shaking hands, and
      therapeutic touch have room for improvement. Targeted interventions focusing on
      norms and expectations of nonverbal behaviors in the U.S. health care setting are
      called for to improve quality of care.

PMID- 23556331
TI  - Differentiation of tannin-containing herbal drugs by HPLC fingerprints.
AB  - A new HPLC system coupled with multiple detectors - Diode array detector (DAD),
      fluorescence detector (FLD), electrochemical amperometric detector (ADC) and mass
      spectrometry detector (MSD) was developed for the characterization and
      differentiation of tannin-containing herbal drugs included in The European
      Pharmacopoeia. The HPLC separation system consisted of an Agilent ZORBAX Eclipse
      XDB C18 column and a gradient water and methanol as the mobile phase which was
      kept at a flow rate of 0.3 mL x min(-1). Four kinds of detectors were connected
      by a micro-splitter valve and simultaneously recorded the response of each
      analytical sample. Thirty-one samples from eight kinds of tannin-containing drugs
      were measured using this HPLC system and their signals from all detectors were
      comprehensively processed via principal component analysis (PCA). The statistic
      result demonstrates that thirty-one batches from different herbal drugs can be
      reasonably identified and systematically classified by their chemical
      fingerprints. The proposed multi-detector HPLC method aided by chemometrics not
      only offers a new pattern for the study of tannin-containing herbs, but also
      provides a useful foundation for quality control of herbal medicines.

PMID- 23556332
TI  - Influence of vehicle properties and excipients on hydrolytic and photochemical
      stability of curcumin in preparations containing Pluronics: studies of curcumin
      and curcuminoids XLVIII.
AB  - The influence of vehicle properties and excipients on the hydrolytic and
      photochemical stability of curcumin in Pluronic preparations, and the
      interactions between curcumin and Pluronics was investigated. Curcumin was found
      to be degraded by general acid-base catalyzed hydrolytic degradation in alkaline
      preparations. The degradation rate of curcumin was higher in carbonate buffer
      than in phosphate buffer (pH 8.8), while it was higher in phosphate buffer than
      in citrate buffer (pH 7.8). At pH 8.0-8.8 the degradation rate of curcumin
      increased compared to preparations with pH <8.0. The stabilizing effect of the
      Pluronics against hydrolytic degradation of curcumin was only detectable at pH
      8.0-8.8, and it was highest for F127 and lowest for P85, in phosphate buffer pH
      8.8. An increase in the ionic strength increased the stabilization against
      hydrolytic degradation of curcumin by all Pluronics. Addition of ethanol
      decreased the hydrolytic stability of curcumin in all Pluronics. Addition of PEG
      400 decreased the hydrolytic stability in preparation with either P123 or F127
      while the degradation in preparations with P85 remained the same as in P85
      preparations without PEG 400. Vehicle properties and excipients did not to any
      large degree influence the spectroscopic properties or the photostability of
      curcumin in Pluronic preparations. Photochemical half life of curcumin was in the
      minutes range. Spectrophotometric data indicate that Pluronic aggregates most
      likely solubilize curcumin through hydrophobic interactions, although hydrogen
      bonding may also be involved.

PMID- 23556333
TI  - Dose-dependent pharmacokinetics of bulleyaconitine A in rats.
AB  - This study was conducted to determine the pharmacokinetic characteristics of
      bulleyaconitine A (BLA) after oral gavage and intravenous administration of BLA
      at a single dose of 0.04, 0.12, 0.36 mg/kg (oral) or 0.02 mg/kg (i.v.) in male
      Sprague-Dawley rats. Plasma concentration profiles were analysed using a non
      compartmental pharmacokinetic method. Following i.v. 0.02 mg/kg and oral
      administration 0.04, 0.12 or 0.36 mg/kg, the geometric mean Cmax values were
      19.97, 2.11, 5.11 and 11.47 ng/ml, respectively; the corresponding geometric mean
      AUC(0-t) values were 10.50, 3.19, 9.59 and 18.10 ng x h/ml, respectively. The
      median Tmax values were 0.033, 0.167, 0.167 and 0.167 h, respectively. The
      terminal elimination half-lives (t1/2) were 1.23, 2.48, 1.93 and 2.17h,
      respectively. The results showed that Cmax and AUC(0-t) increased with increasing
      doses of BLA. The increase in exposure with increasing dose was lower than
      expected under conditions of strict proportionality.

PMID- 23556335
TI  - Hepatotoxicity of sub-nanosized platinum particles in mice.
AB  - Nano-sized materials are widely used in consumer products, medical devices and
      engineered pharmaceuticals. Advances in nanotechnology have resulted in materials
      smaller than the nanoscale, but the biologic safety of the sub-nanosized
      materials has not been fully assessed. In this study, we evaluated the toxic
      effects of sub-nanosized platinum particles (snPt) in the mouse liver. After
      intravenous administration of snPt (15 mg/kg body weight) into mice, histological
      analysis revealed acute hepatic injury, and biochemical analysis showed increased
      levels of serum markers of liver injury and inflammatory cytokines. In contrast,
      administration of nano-sized platinum particles did not produce these
      abnormalities. Furthermore, snPt induced cytotoxicity when directly applied to
      primary hepatocytes. These data suggest that snPt have the potential to induce
      hepatotoxicity. These findings provide useful information on the further
      development of sub-nanosized materials.

PMID- 23556334
TI  - Liquid chromatography-mass spectrometry method for the quantification of
      posaconazole in human plasma: application to pharmacokinetics following single
      dose administration in the fasted state and with a high-fat meal.
AB  - A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed
      to determine concentrations of posaconazole in human plasma precipitated by
      acetonitrile including internal standard. Rapid chromatographic separation was
      achieved in the mobile phase composition of acetonitrile, water and formic acid
      (v/v/v, 55:45:0.1) with a flow rate of 0.25 ml/min. Posaconazole-d4 was used as
      internal standard. Detection was undertaken with cation electrospray tandem mass
      spectrometry on a Sciex/API3000. The method was accurate, specific and sensitive
      for the analysis of posaconazole in human plasma in the concentration range of 2
      1000 ng/ml. The inter- and intra-batch accuracy was within +/- 10% and the lower
      limit of quantification was 2 ng/ml. The method facilitated a clinical
      pharmacokinetic study after oral administration of a single-dose of posaconazole
      suspension in the fasted state and with a high-fat meal in a two-period crossover
      design. Cmax (maximum concentration) and AUC (area under serum drug
      concentration) were significantly increased, and Tmax (time to maximum plasma
      concentration) was delayed under fed condition, which suggested that simultaneous
      administration of posaconazole with food may help to achieve higher plasma
      concentrations and result in better antifungal efficacy.

PMID- 23556336
TI  - CYP2C19 polymorphism and antiplatelet effects of clopidogrel in Chinese stroke
      patients.
AB  - Recently published data indicate that CYP2C19*2 allele is the major determinant
      of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet
      effect of clopidogrel in white or black patients undergoing elective coronary
      stent placement. The conclusion may not be fully generalized or extrapolated to
      the Chinese people due to significantly higher frequencies of the CYP2C19*2 or *3
      variant alleles. We sought to investigate whether the CYP2C19*2 or *3 alleles
      affects platelet reactivity of clopidogrel in Chinese stroke patients. The study
      included 183 consecutive Chinese stroke patients after loading with clopidogrel
      300 mg. Platelet function was assessed by adenosine diphosphate-induced (ADP 20
      micromol/L) platelet aggregation and by light transmittance aggregometry (LTA)
      after seven 75-mg maintenance doses of clopidogrel before discharge. CYP2C19*2 or
      *3 genotypes were determined by time-of-flight mass spectrometer (MALDI/TOF-MS).
      In those patients who were carriers of 1 mutant allele (mutant heterozygotes,
      CYP2C19*1/*2 or *1/*3), ADP-induced maximum platelet aggregation (MPA) were
      significantly different compared with wild-type homozygous patients [37.2% (IQR,
      19.6 to 50.5%) versus 23.6% (IQR, 14.0 to 35.4%), respectively; P=0.002]. In
      addition, in the patients who were carriers of 2 mutant allele (mutant
      homozygotes, CYP2C19*2/*2, *2/*3 or *3/*3,), MPA were also significantly
      different compared with wildtype homozygous patients [35.7% (IQR, 21.0 to 78.1%)
      versus 23.6% (IQR, 14.0 to 35.4%, respectively; P = 0.039]. By multivariable
      linear regression, CYP2C19*2 or *3 loss-of-function alleles were independently
      associated with ADP-induced MPA measurements (partial R2 = 0.138, P = 0.001).
      CYP2C19*2 or *3 allele does link to increased MPA and clopidogrel response.

PMID- 23556337
TI  - CYP2C9*3(1075A > C), ABCB1 and SLCO1B1 genetic polymorphisms and gender are
      determinants of inter-subject variability in pitavastatin pharmacokinetics.
AB  - A pharmacokinetics study was conducted in 12 Chinese volunteers following a
      single dose of 1 mg, 2 mg and 4 mg of pitavastatin calcium in an open-label,
      randomized, three-period crossover design. Plasma concentrations of pitavastatin
      acid and pitavastatin lactone were determined by a HPLC method. Single-nucleotide
      polymorphisms (SNPs) in ABCB1, ABCG2, SLCO1B1, CYP2C9 and CYP3A5 were determined
      by TaqMan (MGB) genotyping assay. An analysis was performed on the relationship
      between the aforementioned SNPs and dose-normalized (based on 1 mg) area under
      the plasma concentration-time curve extrapolated to infinity [AUC(0-infinity)]
      and peak plasma concentration (Cmax) values of the acid and lactone forms of
      pitavastatin. Pitavastatin exhibited linear pharmacokinetics and great inter
      subject variability. Compared to CYP2C9*1/*1 carriers, CYP2C9*1/*3 carriers had
      higher AUC(0-infinity) and Cmax of pitavastatin acid and AUC(0-infinity) of
      pitavastatin lactone (P<0.05). With respect to ABCB1 G2677T/A, non-G carriers had
      higher Cmax and AUC(0-infinity) of pitavastatin acid, and Cmax of pitavastatin
      lactone compared to GT, GA or GG genotype carriers (P<0.05). Gene-dose effects of
      SLCO1B1 c.521T> C and g.11187G > A on pharmacokinetics of the acid and lactone
      forms were observed. Compared to non-SLCO1B1*17 carriers, SLCO1B1*17 carriers had
      higher Cmax and AUC(0-infinity) of the acid and lactone forms (P<0.05).
      Significant sex difference was observed for pharmacokinetics of the lactone.
      Female SLCO1B1 521TT subjects had higher Cmax and AUC(0-infinity) of pitavastatin
      lactone compared to male 521TT subjects, however, such gender difference
      disappeared in 521 TC and 521CC subjects. Pitavastatin pharmacokinetics was not
      significantly affected by ABCB1 C1236T, ABCB1C3435T, CYP3A5*3, ABCG2 c.34G > A,
      c.421C > A, SLCO1B1 c.388A>G, c.571T>C and c.597C>T. We conclude that CYP2C9*3,
      ABCB1 G2677T/A, SLCO1B1 c.521T>C, SLCO1B1 g.11187G > A, SLCO1B1*17 and gender
      contribute to inter-subject variability in pitavastatin pharmacokinetics.
      Personalized medicine should be necessary for hypercholesterolaemic patients
      receiving pitavastatin.

PMID- 23556338
TI  - Interspecies difference of luteolin and apigenin after oral administration of
      Chrysanthemum morifolium extract and prediction of human pharmacokinetics.
AB  - The aims of the present study were to study the interspecies difference in the
      pharmacokinetics of luteolin and apigenin occurring in Chrysanthemum morifolium
      extract (CME) among rats, beagle dogs, mini-pigs, and humans, and compared the
      human pharmacokinetic parameters with the data predicted from the above three
      animals. The plasma concentrations of luteolin and apigenin were determined with
      a RP-HPLC method. An interspecies difference of pharmacokinetics was found,
      especially between rats and other species, the plasma concentration of luteolin
      was much lower than that of apigenin in rats, although the content of luteolin in
      CME was higherthan that of apigenin, whereas the plasma concentration of luteolin
      was much higher than that of apigenin in dogs, mini-pigs and humans. Animal scale
      up of some pharmacokinetic parameters of luteolin and apigenin were also
      performed after rats, beagle dogs, mini-pigs and humans were orally given CME at
      dosages of 400 mg/kg, 102 mg/kg, 90 mg/kg, and 20 mg/kg, respectively. Linear
      relationships were obtained between log mean retention time (MRT) and log species
      body weight (W) (kg), and log elimination half-life (t1/2) (h) and logW. The
      corresponding allometric equations were MRT=9.382W(0.1711) (R2 = 0.9999) and t1/2
      = 4.811W(0.1093) (R2 = 0.9013) for luteolin, MRT = 12.53W(0.0356) (R2 = 0.9980)
      and t1/2 = 7.940W(0.0294) (R2 = 0.9258) for apigenin, respectively. The predicted
      human pharmacokinetic parameters (MRT and t1/2) by an allometric approach were
      18.6 h and 7.46 h for luteolin, 14.3 h and 8.95 h for apigenin, respectively,
      which were close to the values obtained from humans (20 mg CME/kg) in the present
      study. The study has demonstrated the possibility to extrapolate the
      pharmacokinetic behavior of flavonoids from animals to humans.

PMID- 23556339
TI  - IL-10 promoter polymorphisms affect IL-10 production and associate with
      susceptibility to acute myeloid leukemia.
AB  - We investigated the possible association of Interleukin-10 (IL-10) single
      nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia
      (AML) in 115 AML patients and 137 gender- and age-matched controls. Genetic
      analysis of IL-10 SNPs at -819 and -592 was carried out by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Results revealed
      that the -819AA genotype frequencies and the -819A allele frequencies of AML
      group were higher than the controls (59.1% vs 40.9%; 75.6% vs 63.9%,
      respectively); there were remarkable differences in -819T/C and -592A/C gene
      distribution (P<0.05) and the TA haploid frequencies were higher in AML group
      (75.6% vs 63.9%, P<0.05). The IL-10 mRNA expression of AML patients and controls
      with different genotype was detected by Real-time quantitative Polymerase Chain
      Reaction (RT-PCR). IL-10 mRNA expression in incipient AML patients increased
      obviously compared with the non-tumor group and remission group (P<0.05). Further
      analysis suggested that the IL-10 mRNA expression of TA/TA genotype was the
      lowest and CC/CC genotype was the highest; the haploid TA and genotype TA/TA may
      be associated with AML. The research suggested the IL-10 SNPs at -819 and -592
      sites were associated with AML and may affect the IL-10 mRNA expression in AML
      patients in Han people of Hunan province.

PMID- 23556340
TI  - Anticancer activity of the liposome-encapsulated cyclic dipeptides, cyclo(His
      Gly) and cyclo(His-Ala).
AB  - Cyclic dipeptides have been well characterized for their biological activity,
      including antimicrobial and anticancer activities. Cyclo(His-Gly) and cyclo(His
      Ala) have also recently demonstrated significant anticancer activity against a
      range of cell lines, however, as a result of their physicochemistry, namely high
      solubility and low lipophilicity, it can be predicted that cellular permeability
      would be low, making them ideal candidates for liposome drug delivery. Liposomes
      were composed of phosphatidylcholine, hydrogenated soy phosphatidylcholine
      (HSPC), stearylamine, alpha-tocopherol and 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (PEG-DSPE) or folate
      polyethylene glycol-cholesteryl hemisuccinate (F-PEG-CHEMS) using the thin-film
      hydration method and characterized for size and encapsulation. The cytotoxic
      activity of the encapsulated cyclic dipeptides was tested against HeLa, low
      folate HeLa and MCF-7 cells and found to have limited improvement in activity.
      However, modification of the polyethylene glycol with folic acid to target folate
      receptors significantly decreased the IC50 values recorded in all cells lines
      tested, particularly HeLa cells cultured in media containing physiological
      concentrations of folic acid with the lowest IC50 being recorded as 0.0962 mM for
      folate-targeted cyclo(His-Ala). Therefore, hydrophilic cyclic dipeptides are
      ideal candidates for inclusion into targeted drug delivery systems such as
      liposomes.

PMID- 23556341
TI  - MMS 1001 inhibits melanin synthesis via ERK activation.
AB  - Melanin plays major a role in pigmentation of hair, eyes, and skin in mammals. In
      this study, the inhibitory effects of MMS 1001 on alpha-MSH-stimulated
      melanogenesis were investigated in B16F10 melanoma cells. MMS 1001 did not show
      cytotoxic effects up to 10 microM. Melanin content and intracellular tyrosinase
      activity were inhibited by MMS 1001 treatment in a dose-dependent manner. In
      Western blot analysis, MITF expression was decreased by MMS 1001. In addition,
      tyrosinase expressions were also reduced after MMS 1001 treatment. Further
      results showed that the phosphorylation of ERK was induced by MMS 1001. Moreover,
      a specific MEK inhibitor, PD98059, abrogated the inhibitory effects of MMS 1001
      on melanin production and tyrosinase expression. These results indicate that the
      hypopigmentary effects of MMS 1001 resulted from the inhibition of MITF and
      tyrosinase expression via phosphorylation of ERK. Thus, MMS 1001 could be
      developed as a new effective skin-whitening agent.

PMID- 23556342
TI  - Risk factors contributing to urinary protein expression resulting from
      bevacizumab combination chemotherapy.
AB  - Proteinuria following administration of bevacizumab is reported to be a specific
      adverse effect, but the risk factors for proteinuria have not been elucidated. In
      this study, the risk factors for urinary protein expression resulting from
      bevacizumab combination chemotherapy were investigated. The subjects were 47
      patients aged > or = 20 years who had received bevacizumab combination
      chemotherapy at Gifu Municipal Hospital between February 2010 and February 2011.
      A total of 13 patients were excluded based on exclusion criteria; of the
      remaining 34 patients, 24 (70.6%) were assigned to the urinary protein non
      expression group, and 10 (29.4%) were assigned to the urinary protein expression
      group. The results of multivariate logistic regression analysis revealed a
      significant difference in systolic blood pressure (> or =130 mmHg) between the
      two groups (OR: 14.499, 95%CI: 1.326-158.577, p=0.028). This finding shows that
      systolic blood pressure (> or =130 mmHg) is a risk factor for urinary protein
      expression resulting from bevacizumab combination chemotherapy.

PMID- 23556343
TI  - Biological activities of selected basidiomycetes from Yemen.
AB  - In a previous paper we demonstrated the results of biological screening of Yemeni
      basidiomycetes. The present study was aimed to investigate the antimicrobial and
      the antioxidant activity of further basidiomycetes collected in Yemen.
      Dichloromethane, methanol and aqueous extracts of the fruiting bodies of 25
      species were screened in vitro for their antibacterial activities against three
      Gram-positive bacteria (Staphyloccocus aureus, Bacillus subtilis, Micrococcus
      flavus) and two Gram-negative bacteria (Escherichia coli, Pseudomonas
      aeruginosa), against six human fungal pathogens (Candida albicans, Candida
      krusei, Aspergillus fumigatus, Mucor sp., Microsporum gypseum, Trichophyton
      mentagrophytes) and against one non human pathogenic fungus (Candida maltosa).
      The results indicated that 75 extracts exhibited activity against one or more of
      the bacteria. The methanol extracts of Agaricus cf. bernardii, Agrocybe pediades,
      Chlorophyllum molybdites, Coriolopsis polyzona, Ganoderma xylonoides, Pycnoporus
      sanguineus, Trametes lactinea and Trametes cingulata showed activity against all
      tested bacteria. The highest antibacterial activity was exhibited by methanol
      extracts from Chlorophyllum molybdites, Ganoderma xylonoides and Trametes
      cingulata and Agaricus cf. bernardii, Agrocybe pediades, Coriolopsis polyzona,
      Pycnoporus sanguineus and Trametes lactinea. The methanol extracts of
      Chlorophyllum molybdites, Ganoderma xylonoides and Pycnoporus sanguineus showed
      considerable antifungal activities against the tested fungal strains. Strong
      antioxidative effects employing the DPPH assay were exhibited by methanol
      extracts from Chlorophyllum molybdites, Ganoderma xylonoides, Hexagonia velutina,
      Pycnoporus sanguineus, Trametes lactinea and Trametes cingulata. Our previous and
      presented studies about 48 basidiomycetes collected in Yemen provide evidence
      that basidiomycetes from the Arabic region so far should attract more attention
      as potential source for new biologically active agents.

PMID- 23556344
TI  - Hypoglycemic and hypolipidemic effects of a triterpenoid-rich extract from
      Euryale shell on streptozotocin-induced diabetic mice.
AB  - The hypoglycemic and hypolipidemic effects of a triterpenoid-rich extract from
      the Euryale shell (ES) was analyzed in streptozotocin-induced diabetic mice.
      Normal and diabetic mice treated with glimepiride were used as negative and
      positive controls, respectively. Body weight, organ weight index and cholesterol
      related lipid profile parameters were observed after 4 weeks. The hypoglycemic
      activity was assessed by fasting blood glucose (FBG) and fasting insulin (FINS)
      to calculate the insulin sensitivity index (ISI). In addition, the potentially
      regulative mechanisms on insulin resistance were discussed. The results indicated
      that a triterpenoid-rich extract of ES could inhibit reduction in the body weight
      of diabetic mice and regulate glucose metabolism. The hypolipidemic action after
      this extract supplementation was confirmed by significant (p<0.05) decreases in
      the levels of cholesterol, LDL and triglycerides and increase in HDL compared
      with the untreated diabetic mice, especially when using a high dose, which
      suggested that the ES extract could effectively reverse the abnormal enlargement
      of the liver and spleen (p<0.01). The present data suggest that the triterpenoid
      rich extract from the ES has both hypoglycemic and hypolipidemic effects that can
      not only help cure and manage diabetes but also improve insulin resistance (IR).

PMID- 23556345
TI  - The essence of nursing.

PMID- 23556346
TI  - A shift in family-centred NICU care.

PMID- 23556347
TI  - Giving food the attention it deserves.

PMID- 23556348
TI  - The benefits of child obesity prevention programs.

PMID- 23556349
TI  - Dietary sources of saturated fat may influence cardiovascular disease risk.

PMID- 23556350
TI  - Transitioning youth with cecostomy tubes to adult care.

PMID- 23556351
TI  - What's for dinner?

PMID- 23556352
TI  - Retirement: finding the right time to go.

PMID- 23556353
TI  - Get the job done: straight talk about scope of practice.

PMID- 23556354
TI  - Healing trauma, inside and out.

PMID- 23556355
TI  - Leaving employees to their own devices.

PMID- 23556356
TI  - To lead in times of change.

PMID- 23556357
TI  - 2013 session shaping up to be challenging for physicians.

PMID- 23556358
TI  - The road more or less travelled: when I travel this road, the journey is made
      more salient with the AMA riding with me.

PMID- 23556359
TI  - Introduction: planning for change.

PMID- 23556360
TI  - The meaning of white.

PMID- 23556361
TI  - In your experience, are the current changes to medical practice benefitting
      patients?

PMID- 23556362
TI  - How can medical practices be changed to improve patient care?

PMID- 23556363
TI  - What can physicians do to improve health care delivery?

PMID- 23556364
TI  - Is the "patient-centered medical home" (PCMH) a valid concept?

PMID- 23556365
TI  - What do you think healthcare in this country will look like in 2020?

PMID- 23556366
TI  - From your perspective, what are the three most important factors driving this
      transition?

PMID- 23556367
TI  - What non-clinical skills do physicians need to remain viable in the next 3-5
      years?

PMID- 23556368
TI  - How can physicians effectively advocate for their patients, with payors,
      legislators and regulators in this post-reform era?

PMID- 23556369
TI  - Energy drinks and the unwanted buzz: a case report.

PMID- 23556370
TI  - The odyssey of words.

PMID- 23556371
TI  - Restoring a sense of safety in the aftermath of a mass shooting: tips for parents
      and professionals.

PMID- 23556372
TI  - Men's health in urology: disparity or opportunity?

PMID- 23556373
TI  - Male sling procedures for stress urinary incontinence.
AB  - Radical prostatectomy is the most common cause of urinary incontinence in males.
      Urinary slings are a relatively new treatment option for men. This article
      describes two urinary sling procedures as possible surgical approaches for
      incontinence in men.

PMID- 23556375
TI  - Translating an evidence-based algorithm to decrease early post-operative urinary
      retention after urogynecologic surgery.
AB  - The implementation of an evidence-based algorithm along with comprehensive
      nursing education supports effective clinical decision-making in the prevention
      of post-operative urinary retention and bladder distention for women who have
      undergone urogynecologic surgery.

PMID- 23556374
TI  - Including catheter-associated urinary tract infections in the 2008 CMS payment
      policy: a qualitative analysis.
AB  - The study presented in this article addresses the impact of the 2008 nonpayment
      policy of the Centers for Medicare and Medicaid Services (CMS) on catheter
      associated urinary tract infections (CAUTIs) from the perspective of infection
      preventionists. With rich qualitative data, it sheds light on the day-to-day
      impact of this recent health policy on CAUTI prevention.

PMID- 23556376
TI  - The bedside assistant in robotic surgery--keys to success.
AB  - Taking on the position of bedside assistant for a surgical robotic team can be a
      daunting task. Keys to success include preparation, proper operation set up,
      effective use of instruments to augment the actions of the console surgeon, and
      readiness for surgical emergencies. Effective communication, repetitive
      execution, and readiness facilitate the efforts of the surgical team.

PMID- 23556377
TI  - A demonstration of clinical reasoning through a case of scrotal infection.
AB  - Clinical reasoning has been defined as collecting clues, processing information,
      and coming to an understanding of a patient problem, then planning and
      implementing interventions, evaluating outcomes, and reflecting on and learning
      from the process. Clinicians with effective reasoning skills positively impact
      patient outcomes.

PMID- 23556378
TI  - The effectiveness of cranberry products to reduce urinary tract infections in
      females: a literature review.
AB  - Cranberry products, especially cranberry juice, have been posited to prevent or
      treat urinary tract infections (UTIs) in females. Antimicrobial resistance has
      been correlated to repeated antibiotic treatment. Thus, evaluating cranberry
      products as a possible alternative to conventional antibiotic therapy is
      appropriate. This review of the literature evaluated research in which cranberry
      based products are used to prevent or treat UTIs.

PMID- 23556379
TI  - Beverage preferences of your bladder: is it as easy as coffee, tea, or an
      alcoholic beverage?

PMID- 23556380
TI  - An interview with ACHE's 2013-2014 chairman. Interview by Jessica D. Squazzo.

PMID- 23556381
TI  - The power of zero: steps toward high reliability healthcare.

PMID- 23556382
TI  - The power of zero: steps toward high reliability healthcare. South Carolina Safe
      Care Commitment.

PMID- 23556383
TI  - Lists that work: the healthcare leader's role in implementation.

PMID- 23556384
TI  - Energize your organization.

PMID- 23556385
TI  - A three-step process to demonstrate your value.

PMID- 23556386
TI  - Onboarding: moving from "they-sayers" to "we-sayers".

PMID- 23556387
TI  - Addressing the second victims of medical error.

PMID- 23556388
TI  - Moving from a "smack down" to a "speak up" culture. Organization's
      transformational journey improves staff patient satisfaction.

PMID- 23556389
TI  - The benefits of international partnering. Need exists to think in broader terms.

PMID- 23556390
TI  - States must implement three ACA reforms at once. Three mechanisms are insurance
      reforms, Medicaid expansions and state exchanges.

PMID- 23556391
TI  - Addressing generational differences. Study highlights ways senior leaders can
      best coach others to success.

PMID- 23556392
TI  - Healthcare leaders' role in care transitions. Trustee oversight will further
      partnerships in the care continuum.

PMID- 23556393
TI  - Healthy employees, lower premiums and costs. Employers, providers and health
      plans have a new shared aim.

PMID- 23556394
TI  - Patient safety comes first in journey to automate. Technology investment can help
      save live.

PMID- 23556395
TI  - Chapter Benchmarking Study. ACHE assesses how chapters compare to one another.

PMID- 23556396
TI  - The healthcare executive's role in ensuring quality and patient safety.

PMID- 23556397
TI  - Health information confidentiality.

PMID- 23556398
TI  - Connect the dots.

PMID- 23556399
TI  - HIE quality check.

PMID- 23556400
TI  - Synergizing ICD-10.

PMID- 23556401
TI  - Reviewing the new HIPAA rules.

PMID- 23556402
TI  - Transitioning from NwHIN exchange to Healtheway.

PMID- 23556403
TI  - Natural language processing and clinical outcomes: the promise and progress of
      NLP for improved care.

PMID- 23556404
TI  - Breaking free of copy/paste: OIG work plan cracks down on risky documentation
      habit.

PMID- 23556405
TI  - Assessing and improving EHR data quality (updated).

PMID- 23556406
TI  - HHA prospective payment system changes.

PMID- 23556407
TI  - CY 2013 OPPS update.

PMID- 23556408
TI  - The thrombophilic network of autoantibodies in celiac disease.
AB  - BACKGROUND: Celiac disease is a life-long autoimmune condition, affecting
      genetically susceptible individuals that may present with thromboembolic
      phenomena. This thrombophilia represents a puzzle with multiple constituents:
      hyperhomocysteinemia, B12 and?or folate deficiency, methylenetetrahydrofolate
      reductase mutations, and protein C and S deficiency due to vitamin K deficiency.
      However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin
      and antiprothrombin have never been explored in celiac disease. METHODS: The
      serum autoantibody levels were determined in 248 individuals, classified into
      three groups. Group 1 comprised 70 children with definitive celiac disease (age:
      7.04 +/-4.3 years, male to female ratio 1.06) and group 2 comprised 88 normal
      children (age: 6.7 +/-4.17 years, male to female ratio 0.87), representing
      controls. The pediatric populations were compared to group 3, which included 90
      adults who were family members (parents) of group 1 (age: 34.6 +/-11.35 years,
      male to female ratio 1.2). Antibodies were checked by enzyme-linked immunosorbent
      assay. RESULTS: Mean optical density levels of serum
      antiphosphatidylserine/prothrombin immunoglobulin G antibodies were 32.4 +/-19.4,
      3.6 +/-2.5 and 16.1 +/-15.8 absorbance units in groups 1, 2 and 3 respectively (P
      <0.0001), with 45.7%, 0% and 7.8% of groups 1, 2 and 3 respectively positive for
      the antibody (P <0.01). Mean optical density levels of serum
      antiphosphatidylserine/prothrombin immunoglobulin M antibodies were 14.2 +/-8.7,
      6.7 +/-6.4 and 12.4 +/-15.5 absorbance units in groups 1, 2 and 3 respectively (P
      <0.0001), with 7.1%, 3.4% and 9.9% of groups 1, 2 and 3 positive for the
      antibody. Mean optical density levels of serum antiprothrombin and
      antiphospholipid immunoglobulin G antibodies were higher in groups 1 and 3
      compared with 2 (P <0.005) and in groups 1 and 2 compared with 3 (P <0.01),
      respectively. Groups 1, 2 and 3 were positive for antiphospholipid immunoglobulin
      G antibodies (groups 1 and 2 compared with 3) . Celiac disease sera harbor a
      higher antiprothrombin immunoglobulin G level compared with controls.
      CONCLUSIONS: It is suggested that the intestinal injury, endothelial dysfunction,
      platelet abnormality and enhanced apoptosis recently described in celiac disease
      are at the origin of the increased exposure of phospholipids or new epitopes
      representing autoantigens. Those autoantibodies might play a pathogenic role in
      the thrombophilia associated with celiac disease and represent markers for
      potential anticoagulant preventive therapy.

PMID- 23556409
TI  - Simulation studies of structure and edge tension of lipid bilayer edges: effects
      of tail structure and force-field.
AB  - Molecular dynamics simulations of lipid bilayer ribbons have been performed to
      investigate the structures and line tensions associated with free bilayer edges.
      Simulations carried out for dioleoyl phosphatidylcholine with three different
      force-field parameter sets yielded edge line tensions of 45 +/- 2 pN, over 50%
      greater than the most recently reported experimentally determined value for this
      lipid. Edge tensions obtained from simulations of a series of phosphatidylcholine
      lipid bilayer ribbons with saturated acyl tails of length 12-16 carbons and with
      monounsaturated acyl tails of length 14-18 carbons could be correlated with the
      excess area associated with forming the edge, through a two-parameter fit.
      Saturated-tail lipids underwent local thickening near the edge, producing denser
      packing that correlated with lower line tensions, while unsaturated-tail lipids
      showed little or no local thickening. In a dipalmitoyl phosphatidylcholine ribbon
      initiated in a tilted gel-phase structure, lipid headgroups tended to tilt toward
      the nearer edge producing a herringbone pattern, an accommodation that may
      account for the reported edge-induced stabilization of an ordered structure at
      temperatures near a lipid gel-fluid phase transition. 

PMID- 23556410
TI  - SWIVIT--Swiss video-intubation trial evaluating video-laryngoscopes in a
      simulated difficult airway scenario: study protocol for a multicenter prospective
      randomized controlled trial in Switzerland.
AB  - BACKGROUND: Video-laryngoscopes are marketed for intubation in difficult airway
      management. They provide a better view of the larynx and may facilitate tracheal
      intubation, but there is no adequately powered study comparing different types of
      video-laryngoscopes in a difficult airway scenario or in a simulated difficult
      airway situation. METHODS/DESIGN: The objective of this trial is to evaluate and
      to compare the clinical performance of three video-laryngoscopes with a guiding
      channel for intubation (AirtraqTM, A. P. AdvanceTM, King VisionTM) and three
      video-laryngoscopes without an integrated tracheal tube guidance (C-MACTM,
      GlideScopeTM, McGrathTM) in a simulated difficult airway situation in surgical
      patients. The working hypothesis is that each video-laryngoscope provides at
      least a 90% first intubation success rate (lower limit of the 95% confidence
      interval >0.9). It is a prospective, patient-blinded, multicenter, randomized
      controlled trial in 720 patients who are scheduled for elective surgery under
      general anesthesia, requiring tracheal intubation at one of the three
      participating hospitals. A difficult airway will be created using an extrication
      collar and taping the patients' head on the operating table to substantially
      reduce mouth opening and to minimize neck movement. Tracheal intubation will be
      performed with the help of one of the six devices according to randomization.
      Insertion success, time necessary for intubation, Cormack-Lehane grade and
      percentage of glottic opening (POGO) score at laryngoscopy, optimization
      maneuvers required to aid tracheal intubation, adverse events and technical
      problems will be recorded. Primary outcome is intubation success at first
      attempt. DISCUSSION: We will simulate the difficult airway and evaluate different
      video-laryngoscopes in this highly realistic and clinically challenging scenario,
      independently from manufacturers of the devices. Because of the sufficiently
      powered multicenter design this study will deliver important and cutting-edge
      results that will help clinicians decide which device to use for intubation of
      the expected and unexpected difficult airway. TRIAL REGISTRATION: NCT01692535.

PMID- 23556411
TI  - Granulomatous skin lesions on an amputated limb: a typical case of an
      immunocompromised district.

PMID- 23556412
TI  - Review of influenza A virus in swine worldwide: a call for increased surveillance
      and research.
AB  - Pigs and humans have shared influenza A viruses (IAV) since at least 1918, and
      many interspecies transmission events have been documented since that time.
      However, despite this interplay, relatively little is known regarding IAV
      circulating in swine around the world compared with the avian and human knowledge
      base. This gap in knowledge impedes our understanding of how viruses adapted to
      swine or man impacts the ecology and evolution of IAV as a whole and the true
      impact of swine IAV on human health. The pandemic H1N1 that emerged in 2009
      underscored the need for greater surveillance and sharing of data on IAV in
      swine. In this paper, we review the current state of IAV in swine around the
      world, highlight the collaboration between international organizations and a
      network of laboratories engaged in human and animal IAV surveillance and
      research, and emphasize the need to increase information in high-priority
      regions. The need for global integration and rapid sharing of data and resources
      to fight IAV in swine and other animal species is apparent, but this effort
      requires grassroots support from governments, practicing veterinarians and the
      swine industry and, ultimately, requires significant increases in funding and
      infrastructure. 

PMID- 23556414
TI  - A methodological approach to assessing alveolar ridge preservation procedures in
      humans: soft tissue profile.
AB  - INTRODUCTION: The aesthetic results of implant restoration in the anterior
      maxilla are particularly related to the soft tissue profile. Although socket
      preservation techniques appear to reduce bone remodelling after tooth extraction,
      there is still few investigations assessing the external soft tissue profile
      after such procedures. The goal of this study was to describe an accurate
      technique to evaluate soft tissue contour changes after performing socket
      preservation procedures. The secondary objective was to apply the newly developed
      measuring method to a specific socket preservation using a "saddled" connective
      tissue graft combined with the insertion of slowly resorbable biomaterials into
      the socket. MATERIALS AND METHODS: A total of 14 patients needing tooth
      replacement in the aesthetic region were included to receive a socket
      preservation procedure using a connective tissue graft. Impressions were taken
      before the tooth extraction (baseline) and at 2, 4, and 12 weeks after the
      procedure. The corresponding plaster casts were scanned, and the evolution of the
      soft tissue profile in relation to the baseline situation was assessed using
      imaging software. RESULTS: The measuring technique allowed assessing the soft
      tissue profiles accurately at different levels of the alveolar process. The
      insertion of a saddled connective tissue appeared to compensate for the
      horizontal and vertical bone remodelling after a socket preservation procedure in
      most regions of the alveolar crest. After 12 weeks, the only significant change
      was located in the more cervical and central region of the alveolar process and
      reached a median drop of 0.62 mm from baseline. CONCLUSION: Within the
      limitations of this study, we found that a saddled connective tissue graft
      combined with a socket preservation procedure could almost completely counteract
      the bone remodelling in terms of the external soft tissue profile. The minor
      changes found in the cervical region might disappear with the emergence profile
      of the prosthodontic components. The described technique might therefore enhance
      the aesthetic outcomes when a tooth has to be replaced in the aesthetic zone. The
      described protocol can be used to further compare the effectiveness of different
      extraction socket preservation protocols in randomised controlled trials.

PMID- 23556415
TI  - HLA-DPA1*01:11, a well-documented novel allele identified by sequence-based
      typing in three Chinese Han individuals.
AB  - The novel HLA-DPA1*01:11 allele differs from the closest allele DPA1*01:03:01 by
      single nucleotide change at coding sequence nucleotide 242 A>G (codon 50 CAA>CGA)
      in exon 2.

PMID- 23556413
TI  - Designing a multicellular organotypic 3D liver model with a detachable, nanoscale
      polymeric Space of Disse.
AB  - The design of in vitro models that mimic the stratified multicellular hepatic
      microenvironment continues to be challenging. Although several in vitro hepatic
      cultures have been shown to exhibit liver functions, their physiological
      relevance is limited due to significant deviation from in vivo cellular
      composition. We report the assembly of a novel three-dimensional (3D) organotypic
      liver model incorporating three different cell types (hepatocytes, liver
      sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that
      mimics the Space of Disse. The nanoscale interface is detachable, optically
      transparent, derived from self-assembled polyelectrolyte multilayers, and
      exhibits a Young's modulus similar to in vivo values for liver tissue. Only the
      3D liver models simultaneously maintain hepatic phenotype and elicit
      proliferation, while achieving cellular ratios found in vivo. The nanoscale
      detachable polymeric interfaces can be modulated to mimic basement membranes that
      exhibit a wide range of physical properties. This facile approach offers a
      versatile new avenue in the assembly of engineered tissues. These results
      demonstrate the ability of the tri-cellular 3D cultures to serve as an
      organotypic hepatic model that elicits proliferation and maintenance of phenotype
      and in vivo-like cellular ratios. 

PMID- 23556416
TI  - Current pharmacotherapy of nocturia.
AB  - INTRODUCTION: Nocturia is a bothersome urologic symptom and is defined as
      awakening from sleep once or more times to void. The condition is highly
      prevalent in men and women and increases in prevalence with age. Impact on
      quality of life is substantial as is the associated morbidity and mortality.
      AREAS COVERED: A PubMed literature search was undertaken to identify evidence for
      the currently available and utilized pharmacotherapy options for the treatment of
      nocturia. Available pharmacologic treatments include desmopressin, alpha
      blockers, antimuscarinics, and other less commonly utilized therapies.
      Desmopressin is generally found to have high-level evidence to support its use
      for the indication of nocturnal polyuria, a form of nocturia caused by excessive
      nighttime urine production. alpha-blockers and antimuscarinics are generally
      recommended in the setting of benign prostatic hypertrophy in men and overactive
      bladder in both men and women. EXPERT OPINION: Clinical trials addressing
      nocturia often report statistically significant results that do not translate to
      clinically significant reductions in nighttime voids. As a result, the clinical
      utility of these agents has been called into question. Further drug development
      and clinical trials specifically focused on nocturia are needed. Furthermore,
      improved patient-focused assessment tools to measure the impact on symptom
      reduction, improvement in sleep quality, and improvement in quality of life are
      important in understanding what matters most to patients and what outcomes
      translate to patient satisfaction with care.

PMID- 23556417
TI  - Mood-induced variations of mandible and tongue postures.
AB  - Twelve young adults in a good general health were observed during habitual
      posture of tongue and jaw in different emotional conditions induced by watching
      three video sequences. The position of the mandible was tracked by the
      displacements of an electromagnetic sensor glued to the chin. The tongue-to
      palate distance was obtained by 2-D location of three electromagnetic sensors
      placed on the tongue upper midline surface. Head displacements were evaluated
      with a sensor fixed to an upper central incisor and were subtracted from
      corresponding displacements of tongue and chin sensors to obtain the real tongue
      and mandible positions during continuous recording sequences. Emotional
      conditioning by a fear movie influenced the vertical position of the mandible:
      the mean interarch distances during the fear movie (2.34 +/- 0.24 mm) were
      significantly different from those measured during the tender (3.13 +/- 0.35) and
      neutral (3.42 +/- 0.80) movies, respectively (anova repeated measure, SNK; P <
      0.05). anova repeated measure indicated that the tongue-to-palate distance
      differed significantly when the subjects were watching the conditioning movies (P
      = 0.003), the tip of the tongue taking a lower position during the fear movie
      than during the tender and neutral movies.

PMID- 23556418
TI  - Regulatory mechanisms after short- and long-term perturbed lysine biosynthesis in
      the aspartate pathway: the need for isogenes in Arabidopsis thaliana.
AB  - The aspartate-derived amino acid pathway in plants is an intensively studied
      metabolic pathway, because of the biosynthesis of the four essential amino acids
      lysine, threonine, isoleucine and methionine. The pathway is mainly controlled by
      the key regulatory enzymes aspartate kinase (AK; EC 2.7.2.4), homoserine
      dehydrogenase (HSDH; EC 1.1.1.3) and 4-hydroxy-tetrahydrodipicolinate synthase
      (EC 4.3.3.7), formerly referred to as dihydrodipicolinate synthase (DHDPS). They
      are encoded by isoenzyme families and it is not known why such families are
      evolutionarily maintained. To gain more insight into the specific roles and
      regulation of the isoenzymes, we inhibited DHDPS in Arabidopsis thaliana with the
      chemical compound (N,N-dimethylglycinatoboranyloxycarbonylmethyl)-dimethylamine
      borane (DDAB) and compared the short-term effects on the biochemical and
      biomolecular level to the long-term adaptations in dhdps knockout mutants. We
      found that DHDPS2 plays a crucial role in controlling lysine biosynthesis,
      thereby stabilizing flux through the whole aspartate pathway. Moreover, DHDPS2
      was also shown to influence the threonine level to a large extent. In addition,
      the lysine-sensitive AKs, AKLYS1 and AKLYS3 control the short- and long-term
      responses to perturbed lysine biosynthesis in Arabidopsis thaliana. 

PMID- 23556420
TI  - Models for institutional and professional accreditation of haemophilia centres in
      Italy.
AB  - The Health Commission of the Conference between the Italian State and Regions
      recognized the need to establish an institutional accreditation model for
      Haemophilia Centres (HCs) to be implemented by 21 Regions in order to provide
      patients with haemophilia and allied inherited coagulations disorders with high
      and uniform standards of care. The Italian National Blood Centre, on behalf of
      the Commission, convened a panel of clinicians, patients, experts,
      representatives from Regions and Ministry of Health. The agreed methodology
      included: systematic literature review and best practice collection, analysis of
      provisions and regulations of currently available services, priority setting,
      definition of principles and criteria for the development of recommendations on
      the optimal requirements for HCs. The result was the formulation of two
      recommendations sets. Two sets of recommendations were produced. The first
      concerns regional policy planning, in which the following aspects of
      comprehensive haemophilia care should be considered for implementation:
      monitoring and auditing, multidisciplinary approach to clinical care, protocols
      for emergency management, home treatment and its monitoring, patient registries,
      drug availability and procurement, recruitment and training of health care
      professionals. The second set concerns the accreditation process and lists 23
      organizational requirements for level 1 HCs and 4 additional requirements for
      level 2 HCs. These recommendations help to provide Italian Regional Health
      Authorities with an organizational framework for the provision of comprehensive
      care to patients with inherited coagulation disorders based on current scientific
      evidence.

PMID- 23556419
TI  - Silver(I) complex formation with cysteine, penicillamine, and glutathione.
AB  - The complex formation between silver(I) and cysteine (H2Cys), penicillamine
      (H2Pen), and glutathione (H3Glu) in alkaline aqueous solution was examined using
      extended X-ray absorption fine structure (EXAFS) and (109)Ag NMR spectroscopic
      techniques. The complexes formed in 0.1 mol dm(-3) Ag(I) solutions with cysteine
      and penicillamine were investigated for ligand/Ag(I) (L/Ag) mole ratios
      increasing from 2.0 to 10.0. For the series of cysteine solutions (pH 10-11) a
      mean Ag-S bond distance of 2.45 +/- 0.02 A consistently emerged, while for
      penicillamine (pH 9) the average Ag-S bond distance gradually increased from 2.40
      to 2.44 +/- 0.02 A. EXAFS and (109)Ag NMR spectra of a concentrated Ag(I)
      cysteine solution (C(Ag(I)) = 0.8 mol dm(-3), L/Ag = 2.2) showed a mean Ag-S bond
      distance of 2.47 +/- 0.02 A and delta((109)Ag) 1103 ppm, consistent with
      prevailing, partially oligomeric AgS3 coordinated species, while for
      penicillamine (C(Ag(I)) = 0.5 mol dm(-3), L/Ag = 2.0) the mean Ag-S bond distance
      of 2.40 +/- 0.02 A and delta((109)Ag) 922 ppm indicate that mononuclear AgS2
      coordinated complexes dominate. For Ag(I)-glutathione solutions (C(Ag(I)) = 0.01
      mol dm(-3), pH ~11), mononuclear AgS2 coordinated species with a mean Ag-S bond
      distance of 2.36 +/- 0.02 A dominate for L/Ag mole ratios from 2.0 to 10.0. The
      crystal structure of the silver(I)-cysteine compound (NH4)Ag2(HCys)(Cys).H2O (1)
      precipitating at pH ~10 was solved and showed a layer structure with both AgS3
      and AgS3N coordination to the cysteinate ligands. A redetermination of the
      crystal structure of Ag(HPen).H2O (2) confirmed the proposed digonal AgS2
      coordination environment to bridging thiolate sulfur atoms in polymeric
      intertwining chains forming a double helix. A survey of Ag-S bond distances for
      crystalline Ag(I) complexes with S-donor ligands in different AgS2, AgS2(O/N),
      and AgS3 coordination environments was used, together with a survey of (109)Ag
      NMR chemical shifts, to assist assignments of the Ag(I) coordination in solution.

PMID- 23556421
TI  - Working towards best practice in communicating health economics research.

PMID- 23556422
TI  - A cost-effectiveness analysis of subcutaneous interferon beta-1a 44mcg 3-times a
      week vs no treatment for patients with clinically isolated syndrome in Sweden.
AB  - OBJECTIVE: To assess the cost-effectiveness of subcutaneous interferon (sc IFN)
      beta-1a 44 mcg 3-times weekly (tiw) vs no treatment at reducing the risk of
      conversion to multiple sclerosis (MS) in patients with clinically isolated
      syndrome (CIS) in Sweden. METHODS: A Markov model was constructed to simulate the
      clinical course of patients with CIS treated with sc IFN beta-1a 44 mcg tiw or no
      treatment over a 40-year time horizon. Costs were estimated from a societal
      perspective in 2012 Swedish kronor (SEK). Treatment efficacy data were derived
      from the REFLEX trial; resource use and quality-of-life (QoL) data were obtained
      from the literature. Costs and outcomes were discounted at 3%. Sensitivity
      analyses explored whether results were robust to changes in input values and use
      of Poser criteria. RESULTS: Using McDonald criteria sc IFN beta-1a was cost
      saving and more effective (i.e., dominant) vs no treatment. Gains in progression
      free life years (PFLYs) and quality-adjusted life-years (QALYs) were 1.63 and
      0.53, respectively. Projected cost savings were 270,263 SEK. For Poser criteria
      cost savings of 823,459 SEK were estimated, with PFLY and QALY gains of 4.12 and
      1.38, respectively. Subcutaneous IFN beta-1a remained dominant from a payer
      perspective. Results were insensitive to key input variation. Probabilistic
      sensitivity analysis estimated a 99.9% likelihood of cost-effectiveness at a
      willingness-to-pay threshold of 500,000 SEK/QALY. CONCLUSION: Subcutaneous IFN
      beta-1a is a cost-effective option for the treatment of patients at high risk of
      MS conversion. It is associated with lower costs, greater QALY gains, and more
      time free of MS. LIMITATIONS: The risk of conversion from CIS to MS was
      extrapolated from 2-year trial data. Treatment benefit was assumed to persist
      over the model duration, although long-term data to support this are unavailable.
      Cost and QoL data from MS patients were assumed applicable to CIS patients.

PMID- 23556423
TI  - Slithering snakes, angry men and out-group members: what and whom are we evolved
      to fear?
AB  - The preparedness theory of classical conditioning proposed by Seligman (1970,
      1971) has been applied extensively over the past 40 years to explain the nature
      and "source" of human fear and phobias. In this review we examine the formative
      studies that tested the four defining characteristics of prepared learning with
      animal fear-relevant stimuli (typically snakes and spiders) and consider claims
      that fear of social stimuli, such as angry faces, or faces of racial out-group
      members, may also be acquired utilising the same preferential learning mechanism.
      Exposition of critical differences between fear learning to animal and social
      stimuli suggests that a single account cannot adequately explain fear learning
      with animal and social stimuli. We demonstrate that fear conditioned to social
      stimuli is less robust than fear conditioned to animal stimuli as it is
      susceptible to cognitive influence and propose that it may instead reflect on
      negative stereotypes and social norms. Thus, a theoretical model that can
      accommodate the influence of both biological and cultural factors is likely to
      have broader utility in the explanation of fear and avoidance responses than
      accounts based on a single mechanism. 

PMID- 23556426
TI  - Fibrosarcomatous variant of dermatofibrosarcoma protuberans with pancreatic
      metastasis.

PMID- 23556424
TI  - Adalimumab for orbital myositis in a patient with Crohn's disease who
      discontinued infliximab: a case report and review of the literature.
AB  - BACKGROUND: Orbital myositis is a rare extra-intestinal manifestation of
      inflammatory bowel disease. Seventeen cases of Crohn's disease associated orbital
      myositis and 3 cases of ulcerative colitis associated orbital myositis have been
      reported in the published literature since 1970. We report the use of adalimumab
      (Abbott, Canada, Inc.) for orbital myositis in a patient with Crohn's disease who
      discontinued infliximab (Janssen, Canada, Inc.) and review of the published
      literature. CASE PRESENTATION: A 35 year-old male with a 7-year history of
      Crohn's disease was treated with an ileocolonic resection and re-anastomosis
      followed by infliximab which maintained full endoscopic and clinical remission
      for four years. After stopping the infliximab for infusion-related reactions he
      presented with 3-day history of severe right eye pain, pain with ocular movement,
      proptosis, and conjunctival injection. He had no intestinal symptoms and
      endoscopic assessment revealed no active luminal disease. CT of the orbit
      revealed an enlarged right medial rectus muscle with tendonous involvement and a
      diagnosis of orbital myositis was made. Treatment with 80 mg per day prednisone
      with tapering dose and adalimumab, induction and maintenance, resulted in rapid
      resolution of the orbital myositis and ocular symptoms with no recurrences on
      follow-up at 10 months. CONCLUSIONS: The current case demonstrates a rare
      extraintestinal manifestation of Crohn's disease, orbital myositis, and its
      temporal relationship to the discontinuance of infliximab therapy and its
      successful treatment, without recurrence with tapering prednisone and adalimumab.

PMID- 23556425
TI  - Attributable costs of ventilator-associated lower respiratory tract infection
      (LRTI) acquired on intensive care units: a retrospectively matched cohort study.
AB  - BACKGROUND: Lower respiratory tract infections (LRTI) are the most common
      hospital-acquired infections on ICUs. They have not only an impact on each
      patient's individual health but also result in a considerable financial burden
      for the healthcare system. Our aim was to determine the costs and the length of
      stay of patients with ICU-acquired LRTI. METHODS: We used a retrospectively
      matched cohort design, comparing patients with ICU-acquired LRTI and ICU patients
      without LRTI. LRTI was diagnosed using the definitions of the Centers for Disease
      Control and Prevention (CDC). Study period was from January to December 2010
      analyzing patients from 10 different ICUs (medical, surgical, interdisciplinary).
      The device utilization ratio was defined as number of ventilator days divided by
      number of patient days and the device-associated LRTI rate was defined as number
      of ventilator associated LRTI divided by number of ventilator days. Patients were
      matched by age, sex, and prospectively obtained Simplified Acute Physiology Score
      II (SAPS II). The length of ICU stay of control patients needed to be at least as
      long as that of LRTI-patients before onset of LRTI. We used the Wilcoxon signed
      rank test for continuous variables and the McNemar's test for categorical
      variables. RESULTS: The analyzed ICUs had 40,772 patient days in the study period
      with a median ventilation utilization ratio of 56 (IQR 42-65). The median device
      associated LRTI rate was 3.35 (IQR 0.96-5.36) per 1,000 ventilation days. We
      analyzed 49 patients with ICU-acquired LRTI and 49 respective controls without
      LRTI. The median hospital costs for LRTI patients were significantly higher than
      for patients without LRTI (45,041 ? vs. 26,467 ?; p < .001). The attributable
      costs per LRTI patient were 17,015 ? (p < .001). Patients with ICU acquired LRTI
      stayed longer in the hospital than patients without (36 days vs. 24 days; p =
      0.011). An LRTI lead to an attributable increase in length of stay by 9 days (p =
      0.011). CONCLUSIONS: ICU-acquired LRTI is associated with increased hospital
      costs and prolonged hospital stay. Hospital management should therefore implement
      control measurements to keep the incidence of ICU-acquired LRTI as low as
      possible.

PMID- 23556427
TI  - Cycloaddition of chiral tert-butanesulfinimines with trimethylenemethane.
AB  - The cycloaddition of chiral tert-butanesulfinimines with trimethylenemethane is
      found to give facile access to methylene-pyrrolidines with good yields and
      diastereoselectivities. The full scope of the cycloaddition is explored, and a
      range of transformations of the formed methylenepyrrolidines to give a range of
      functionalized chiral pyrrolidines is presented.

PMID- 23556428
TI  - Spatial-temporal variations of Schistosoma japonicum distribution after an
      integrated national control strategy: a cohort in a marshland area of China.
AB  - BACKGROUND: Schistosomiasis transmission is typically focal. Understanding
      spatial variations of Schistosoma infections and their associated factors is
      important to help to invent site-specific intervention strategies. METHODS: A
      five-year longitudinal study was carried out prospectively in 12 natural
      villages, Guichi district of Anhui province. A GIS-based spatial analysis was
      conducted to identify geographic distribution patterns of schistosomiasis
      infections at the household scale. RESULTS: The results of the spatial
      autocorrelation analysis for 2005 showed that there were significant spatial
      clusters of human infections at the household level, and these results were in
      agreement with that of the spatial scan statistic. As prevalence of infections in
      humans decreased over the course of control, the spatial distribution of these
      infections became less heterogeneous. CONCLUSIONS: The findings imply that it may
      be necessary to re-assess risk factors of S. japonicum transmission over the
      course of control and to adjust accordingly control measures in the communities.

PMID- 23556429
TI  - Is overweight at 12 months associated with differences in eating behaviour or
      dietary intake among children selected for inappropriate bottle use?
AB  - Bottle feeding beyond the recommended weaning age of 12 months is a risk factor
      for childhood obesity. This paper describes a sample of toddlers at high risk for
      obesity: prolonged bottle users from a low-income multi-ethnic community. We
      report here baseline mealtime and feeding behaviour, 24 h dietary recall and
      bottle intake data for Feeding Young Children Study (FYCS) participants, by
      overweight (>=85% weight-for-length) status. FYCS enrolled 12-13-month-olds from
      urban nutrition programmes for low-income families in the United States who were
      consuming >=2 bottles per day. Our sample was predominately Hispanic (62%), 44%
      of mothers were born outside of the United States and 48% were male. Overall, 35%
      were overweight. Overweight status was not associated with mealtime/feeding
      behaviours, bottle use or dietary intake. Most (90%) children ate enough, were
      easily satisfied and did not exhibit negative (e.g. crying, screaming) mealtime
      behaviours, per parent report. The sample's median consumption of 4 bottles per
      day accounted for 50% of their total calories; each bottle averaged 7 ounces and
      contained 120 calories. Mean daily energy intake, 1098.3 kcal day(-1) (standard
      deviation = 346.1), did not differ by weight status, nor did intake of fat,
      saturated fat, protein or carbohydrates. Whole milk intake, primarily consumed
      via bottles, did not differ by weight status. Thus, overweight 12-13-month-olds
      in FYCS were remarkably similar to their non-overweight peers in terms of several
      obesity risk factors. Findings lend support to the set-point theory and prior
      work finding that weight and intake patterns in the first year of life alter
      subsequent obesity risk. 

PMID- 23556430
TI  - Growth and development of children aged 1-5 years in low-intensity armed conflict
      areas in Southern Thailand: a community-based survey.
AB  - BACKGROUND: A low-intensity armed conflict has been occurring for nearly a decade
      in southernmost region of Thailand. However, its impact on child health has not
      yet been investigated. This study aimed to estimate the prevalence of delayed
      child growth and development in the affected areas and to determine the
      association between the violence and health among children aged 1-5 years.
      METHODS: A total of 498 children aged 1-5 years were recruited. Intensity of
      conflict for each sub-district was calculated as the 6-year average number of
      incidents per 100,000 population per year and classified into quartiles. Growth
      indices were weight-for-age, height-for-age, and weight-for-height, while
      development was measured by the Denver Development Screening Test II (Thai
      version). Food insecurity, child-rearing practice, health service accessibility,
      household sanitation, and depression among the caregivers were assessed using
      screening scales and questionnaires. Contextual information such as average
      income and numbers of violent events in each sub-district was obtained from
      external sources. RESULTS: Growth retardation was highly prevalent in the area as
      reported by rates of underweight, stunting, and wasting at 19.3%, 27.6% and 7.4%,
      respectively. The prevalence of developmental delay was also substantially high
      (37.1%). Multi-level analysis found no evidence of association between insurgency
      and health outcomes. However, children in areas with higher intensity of violence
      had a lower risk of delay in personal-social development (OR = 0.4; 95% CI = 0.2 
      0.9; p-value = 0.05). CONCLUSION: Unlike war refugees and internally-displaced
      persons in camp-like settings, the relationship between level of armed conflict
      and growth and developmental delay among children aged 1-5 years could not be
      demonstrated in the community setting of this study where food supply had been
      minimally perturbed.

PMID- 23556431
TI  - Activity of histone deacetylase inhibitors and an Aurora kinase inhibitor in BCR
      ABL-expressing leukemia cells: Combination of HDAC and Aurora inhibitors in BCR
      ABL-expressing cells.
AB  - BACKGROUND: The use of imatinib, an ABL tyrosine kinase inhibitor, has led to a
      dramatic change in the management of BCR-ABL-positive leukemia patients. However,
      resistance to imatinib mediated by mutations in the BCR-ABL domain has become a
      major problem in the treatment of these patients. METHODS: In the present study,
      we examined the activity of histone deacetylase (HDAC) inhibitors in combination
      with an Aurora kinase inhibitor in BCR-ABL-expressing cells. RESULTS: We found
      the HDAC inhibitors vorinostat and/or pracinostat (SB939) induced apoptosis in
      BCR-ABL-expressing cells. Additionally, HDAC inhibitors reduced levels of Aurora
      A and B protein. An Aurora kinase inhibitor, tozasertib (VX-680), inhibited
      growth, promoted pro-apoptotic activity, reduced the phosphorylation of BCR-ABL
      and Crk-L, and activated caspase-3 and poly (ADP-ribose) polymerase (PARP) in BCR
      ABL-positive cells. Moreover, after treatment with tozasertib, HDAC protein
      expression was decreased. Combination of vorinostat or pracinostat with
      tozasertib had a synergistic inhibitory effect on the proliferation of T315I
      cells. Phosphorylation of Crk-L decreased, and PARP activation increased after
      treatment with vorinostat or pracinostat and tozasertib. Moreover, combination of
      vorinostat or pracinostat and tozasertib significantly increased the extent of
      apoptosis in primary chronic myeloid leukemia cells. CONCLUSIONS: This study
      demonstrated that combination of HDAC and Aurora inhibitors was highly effective
      against BCR-ABL-expressing cells.

PMID- 23556432
TI  - 16/6-idiotype expressing antibodies induce brain inflammation and cognitive
      impairment in mice: the mosaic of central nervous system involvement in lupus.
AB  - BACKGROUND: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found
      to induce experimental lupus in naive mice, manifested by production of
      autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney
      and brain involvement. We assessed behavior and brain pathology of naive mice
      injected intra-cerebra-ventricularly (ICV) with the 16/6-Id antibody. METHODS:
      C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id
      antibody or commercial human IgG antibodies (control). The mice were tested for
      depression by the forced swimming test (FST), locomotor and explorative activity
      by the staircase test, and cognitive functions were examined by the novel object
      recognition and Y-maze tests. Brain slices were stained for inflammatory
      processes. RESULTS: 16/6-Id injected mice were cognitively impaired as shown by
      significant differences in the preference for a new object in the novel object
      recognition test compared to controls (P = 0.012). Similarly, the preference for
      spatial novelty in the Y-maze test was significantly higher in the control group
      compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065).
      Depression-like behavior and locomotor activity were not significantly different
      between the16/6-Id-injected and the control mice. Immunohistochemistry analysis
      revealed an increase in astrocytes and microglial activation in the hippocampus
      and amygdala, in the 16/6-Id injected group compared to the control. CONCLUSIONS:
      Passive transfer of 16/6-Id antibodies directly into mice brain resulted in
      cognitive impairments and histological evidence for brain inflammation. These
      findings shed additional light on the diverse mosaic pathophysiology of
      neuropsychiatric lupus.See related Commentary article:
      http://www.biomedcentral.com/1741-7015/11/91.

PMID- 23556433
TI  - Left thigh phlegmon caused by Nocardia farcinica identified by 16S rRNA
      sequencing in a patient with leprosy: a case report.
AB  - BACKGROUND: In recent years, Nocardia farcinica has been reported to be an
      increasingly frequent cause of localized and disseminated infections in the
      immunocompromised patient. However, recent literature is limited. We report a
      case of left thigh phlegmon caused by N. farcinica that occurred in a patient
      with leprosy undergoing treatment with prednisone for leprosy reaction. CASE
      PRESENTATION: We describe the case of left thigh phlegmon caused by Nocardia
      farcinica in a 54-year-old Italian man affected by multi-bacillary leprosy. The
      patient had worked in South America for 11 years. Seven months after his return
      to Italy, he was diagnosed with leprosy and started multi-drug antibiotic therapy
      plus thalidomide and steroids. Then, during therapy with rifampicin monthly,
      minocycline 100 mg daily, moxifloxacin 400 mg daily, and prednisone (the latter
      to treat type 2 leprosy reaction), the patient complained of high fever
      associated with erythema, swelling, and pain in the left thigh. Therefore, he was
      admitted to our hospital with the clinical suspicion of cellulitis. Ultrasound
      examination and Magnetic Resonance Imaging showed left thigh phlegmon. He was
      treated with drainage and antibiotic therapy (meropenem and vancomycin replaced
      by daptomycin). The responsible organism, Nocardia farcinica, was identified by
      16S rRNA sequencing in the purulent fluid taken out by aspiration. The patient
      continued treatment with intravenous trimethoprim/sulfamethoxazole and imipenem
      followed by oral trimethoprim/sulfamethoxazole and moxifloxacin. A whole-body
      computed tomography did not reveal dissemination to other organs like the lung or
      brain.The patient was discharged after complete remission. Oral therapy with
      trimethoprim/sulfamethoxazole, moxifloxacin, rifampicin monthly, clofazimine and
      thalidomide was prescribed to be taken at home. One month after discharge from
      the hospital the patient is in good clinical condition with complete resolution
      of the phlegmon. CONCLUSION: N. farcinica is a rare infectious agent that mainly
      affects immunocompromised patients. Presentation of phlegmon only without
      disseminated infection is unusual, even in these kinds of patients. In any case,
      a higher index of suspicion is needed, as diagnosis can easily be missed due to
      the absence of characteristic symptoms and the several difficulties usually
      encountered in identifying the pathogen.

PMID- 23556434
TI  - The Healthy Lifestyles Programme (HeLP), a novel school-based intervention to
      prevent obesity in school children: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Over the last three decades there has been a substantial increase in
      the proportion of children who are overweight or obese. The Healthy Lifestyles
      Programme (HeLP) is a novel school-based intervention, using highly interactive
      and creative delivery methods to prevent obesity in children. METHODS/DESIGN: We
      describe a cluster randomised controlled trial to evaluate the effectiveness and
      cost effectiveness of HeLP. The intervention has been developed using
      intervention mapping (involving extensive stakeholder involvement) and has been
      guided by the Information, Motivation, Behavioural Skills model. HeLP includes
      creating a receptive environment, drama activities, goal setting and
      reinforcement activities and runs over three school terms. Piloting showed that 9
      to 10 year olds were the most receptive and participative. This study aims to
      recruit 1,300 children from 32 schools (over half of which will have >=19% of
      pupils eligible for free school meals) from the southwest of England.
      Participating schools will be randomised to intervention or control groups with
      baseline measures taken prior to randomisation. The primary outcome is change in
      body mass index standard deviation score (BMI SDS) at 24 months post baseline.
      Secondary outcomes include, waist circumference and percent body fat SDS and
      proportion of children classified as overweight or obese at 18 and 24 months and
      objectively measured physical activity and food intake at 18 months. Between
      group comparisons will be made using random effects regression analysis taking
      into account the hierarchical nature of the study design. An economic evaluation
      will estimate the incremental cost-effectiveness of HeLP, compared to control,
      from the perspective of the National Health Service (NHS)/third party payer. An
      in-depth process evaluation will provide insight into how HeLP works, and whether
      there is any differential uptake or engagement with the programme. DISCUSSION:
      The results of the trial will provide evidence on the effectiveness and cost
      effectiveness of the Healthy Lifestyles Programme in affecting the weight status
      of children. TRIAL REGISTRATION: ISRCTN15811706.

PMID- 23556435
TI  - Development of a scale to measure stigma related to podoconiosis in Southern
      Ethiopia.
AB  - BACKGROUND: Health-related stigma adds to the physical and economic burdens
      experienced by people suffering from neglected tropical diseases (NTDs). Previous
      research into the NTD podoconiosis showed significant stigma towards those with
      the disease, yet no formal instrument exists by which to assess stigma or
      interventions to reduce stigma. We aimed to develop, pilot and validate scales to
      measure the extent of stigma towards podoconiosis among patients and in
      podoconiosis-endemic communities. METHODS: Indicators of stigma were drawn from
      existing qualitative podoconiosis research and a literature review on measuring
      leprosy stigma. These were then formulated into items for questioning and
      evaluated through a Delphi process in which irrelevant items were discounted. The
      final items formed four scales measuring two distinct forms of stigma (felt
      stigma and enacted stigma) for those with podoconiosis and those without the
      disease. The scales were formatted as two questionnaires, one for podoconiosis
      patients and one for unaffected community members. 150 podoconiosis patients and
      500 unaffected community members from Wolaita zone, Southern Ethiopia were
      selected through multistage random sampling to complete the questionnaires which
      were interview-administered. The scales were evaluated through reliability
      assessment, content and construct validity analysis of the items, factor analysis
      and internal consistency analysis. RESULTS: All scales had Cronbach's alpha over
      0.7, indicating good consistency. The content and construct validity of the
      scales were satisfactory with modest correlation between items. There was
      significant correlation between the felt and enacted stigma scales among patients
      (Spearman's r = 0.892; p < 0.001) and within the community (Spearman's r = 0.794;
      p < 0.001). CONCLUSION: We report the development and testing of the first
      standardised measures of podoconiosis stigma. Although further research is needed
      to validate the scales in other contexts, we anticipate they will be useful in
      situational analysis and in designing, monitoring and evaluating interventions.
      The scales will enable an evidence-based approach to mitigating stigma which will
      enable implementation of more effective disease control and help break the cycle
      of poverty and NTDs.

PMID- 23556436
TI  - Effects of exogenous enzymes and dietary energy on performance and digestive
      physiology of broilers.
AB  - The study was conducted to compare the effects of XG with AG and BM at different
      metabolizable energy diets on growth performance, digestive physiology and energy
      utilization of broilers fed with corn-SBM diet. A 2 * 4 factorial design was used
      with two basal diets (the positive control group, PC; negative control with ME
      reduction 100 kcal/kg, NC) and with or without the addition of three exogenous
      enzymes (0.02% BM; 0.01% AG; 0.05% XG) respectively. 1,200 one-day-old broilers
      were randomly allocated to 8 treatments with 10 pens of 15 broilers. There was no
      significant difference on BW, BWG, and FI at 0-21d, 21-42d or 0-42d for diet,
      enzymes or their interactions, but FI at 22-42d and 0-42d were tend to be
      decreased with the addition of enzymes. The F/G was significantly improved by the
      addition of enzymes especially in NC diet. The dietary AME and TME in PC or NC
      diet were significantly increased by XG or AG in NC diet. The villus length and
      V/C of ileum were significantly increased by the addition of BM or XG. XG
      improved the activities of trypsin, chymotrypsin and amylase, BM improved the
      activity of trypsin at 21d, and AG improved the activity of chymotrypsin at 21d.
      Comparing to PC diet, the addition of enzymes in PC or NC diet decreased feed
      cost per kg body weight gain especially in NC diet (except AG in PC diet) with
      the highest profits for XG in NC diet. In conclusion, supplementation of 0.02% BM
      or 0.01% AG or 0.05% XG could improve feed conversion of broilers in corn-soybean
      meal diet by improving energy utilization and digestive physiology, and also
      supplementation of 0.05% XG had a preferable efficacy in low energy diet. 

PMID- 23556438
TI  - Rovibrational energies of the hydrocarboxyl radical from a RCCSD(T) study.
AB  - A RCCSD(T)/cc-pVQZ potential energy surface is constructed for the HOCO radical
      in the ground electronic state and used to compute rotation-vibration levels of
      HOCO and DOCO. Two numerical strategies are employed to study in detail the wave
      function properties. The importance of stretch-bend coupling, such as nu4/nu5 and
      nu3/nu4, for the internal dynamics is demonstrated. The rotational constants
      computed for the vibrational ground state of trans and cis conformers are in good
      agreement with experimental values. 

PMID- 23556437
TI  - Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein
      genotypes after vitamin D3 or D2supplementation.
AB  - BACKGROUND: It is not known whether genetic variation in the vitamin D binding
      protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D
      supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D3
      and 25(OH)D2 in a Thai cohort, according to type of vitamin D supplement (vitamin
      D3 or D2) and DBP genotype, after receiving vitamin D3 or D2 for 3 months.
      METHODS: Thirty-nine healthy subjects completed the study. All subjects received
      400  IU of either vitamin D3 or D2, plus a calcium supplement, every day for 3
      months. Total serum 25(OH)D, 25(OH)D3 and 25(OH)D2 were measured by LC-MS/MS.
      Individual genotyping of rs4588 in the DBP gene was performed using real-time
      PCR. RESULTS: Vitamin D3 supplementation of 400  IU/d increased 25(OH)D3
      significantly (+16.2 +/- 4.2 nmol/L, p <0.001). Vitamin D2 (400 IU/d) caused
      increased 25(OH)D2 levels (+22.0 +/- 2.11 nmol/L, p <0.001), together with a
      decrease of 25(OH)D3 (-14.2 +/- 2.0 nmol/L, p <0.001). At 3 month, subjects in
      vitamin D3 group tended to have higher total 25(OH)D levels than those in vitamin
      D2 (67.8 +/- 3.9 vs. 61.0 +/- 3.0 nmol/L; p = 0.08). Subjects were then
      classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and
      the rest (CA or AA). With D3 supplementation, subjects with CA or AA alleles had
      significantly less increase in 25(OH)D3 and total 25(OH)D when compared with
      those with the CC allele. However, no difference was found when the supplement
      was vitamin D2. CONCLUSION: Genetic variation in DBP (rs4588 SNP) influences
      responsiveness to vitamin D3 but not vitamin D2.

PMID- 23556439
TI  - Assessment of cervical length by transvaginal ultrasonography to predict preterm
      delivery in twin pregnancy.
AB  - OBJECTIVE: In singleton pregnancy, short cervix is associated with the risk of
      spontaneous preterm delivery (SPD). On the other hand, twin pregnancy increases
      rate of preterm delivery, so this study was designed to evaluate the transvaginal
      sonographic (TVS) measurement of cervical length (CL) to predict preterm birth in
      twin pregnancy. METHODS: This prospective cohort study was performed on 80 twin
      pregnant women whom the length and funneling of their cervix were evaluated
      between 22-24 gestational weeks by (TVS). They referred to us at the early signs
      of labor. Then the gestational age at delivery was recorded. The Fisher exact
      test and the odds-ratio was used to determine the association between CL and SPD.
      RESULTS: Thirty-four (42.5%) women had SPD. Cervical funneling happened in 7.5%
      of cases and SPD occurred in all women with funneling. There was a significant
      correlation between CL <= 30 mm and SPD (66.7% versus 35.5%, p = 0.029) Also, the
      risk of SPD was enhanced 3.6 times with CL <= 30 mm, CI 95% (1.1-11). CONCLUSION:
      We recommend TVS for assessment of CL between 22-24 weeks for prediction of SPD
      in twin pregnancy.

PMID- 23556440
TI  - Lymphoblastoid cell lines in pharmacogenomics: how applicable are they to
      clinical outcomes?

PMID- 23556441
TI  - Osteoporosis pharmacogenomics: recent insights and future perspectives.

PMID- 23556443
TI  - Combining genetic variations in CYP2C9 and VKORC1 with clinical factors for
      warfarin dosing determination improved clinical effectiveness.

PMID- 23556444
TI  - Institutional Profile: Jayne Haines Center for Pharmacogenomics and Drug Safety:
      educating future generations of healthcare professionals.
AB  - The Jayne Haines Center for Pharmacogenomics and Drug Safety operates in the
      Temple University School of Pharmacy and serves as an educational and research
      facility for professional pharmacy students, graduate students, residents,
      postdoctoral fellows and faculties. The Center is involved in educational and
      investigational projects in a setting that includes an inner city
      research/teaching hospital and the Temple University Schools of Pharmacy,
      Medicine, Dentistry and Health Professions. The mission of the Haines Center is
      to facilitate the basic science approach to the problems of pharmacotherapy, and
      to provide education for future healthcare professionals in the genetics of drug
      response. With the expanding role of genetic analysis in preventing adverse
      effects of pharmacotherapy, we are working towards truly personalized
      pharmacotherapy that fully exploits the advances of modern biomedical science.

PMID- 23556445
TI  - Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease
      severity and hydroxyurea treatment efficacy.
AB  - AIM: In this study we explored the association between genetic variations in
      MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in beta
      hemoglobinopathy patients, as well as the association between these variants with
      response to hydroxyurea (HU) treatment. Furthermore, we examined MAP3K5
      expression in the context of high fetal hemoglobin (HbF) and upon HU treatment in
      erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals.
      MATERIALS & METHODS: For this purpose, we genotyped beta-thalassemia intermedia
      and major patients and healthy controls, as well as a cohort of compound
      heterozygous sickle cell disease/beta-thalassemia patients receiving HU as HbF
      augmentation treatment. Furthermore, we examined MAP3K5 expression in the context
      of high HbF and upon HU treatment in erythroid progenitor cells from healthy and
      KLF1 haploinsufficient individuals. RESULTS: A short tandem repeat in the MAP3K5
      promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are
      associated with low HbF levels and a severe disease phenotype. Moreover, MAP3K5
      mRNA expression levels are altered in the context of high HbF and are affected by
      the presence of HU. Lastly, the abovementioned MAP3K5 variants are associated
      with HU treatment efficacy. CONCLUSION: Our data suggest that these MAP3K5
      variants are indicative of beta-thalassemia disease severity and response to HU
      treatment.

PMID- 23556446
TI  - Association of ATP-binding cassette transporter variants with the risk of
      Alzheimer's disease.
AB  - AIM: A number of studies have demonstrated that ABCB1 and BCRP (ABCG2) actively
      transport Abeta. We aimed to investigate the association of genetic variants of
      selected multidrug transporters with Alzheimer's disease (AD) in
      histopathologically confirmed AD cases and controls. MATERIALS & METHODS: DNA
      from brain tissue of 71 AD cases with Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD) neuropathological stages B/C and 81 controls was
      genotyped for selected variants in ABCA1, ABCA7, ABCB1, ABCC2 and ABCG2. In
      addition, the APOE4 status was analyzed. RESULTS: The novel ABCA7 SNP, rs3752246,
      tended to be associated with AD in our study. Variants in ABCB1 were
      significantly less frequent in AD cases older than 65 years of age and among
      females. This association of ABCB1 2677G>T (rs2032582) was more pronounced in
      APOE4-negative cases (p = 0.005). However, only ABCC2 3972C>T (rs3740066) was
      significantly associated with AD risk after logistic regression analysis
      including all variants. Other transporters showed a lack of association.
      CONCLUSION: Our results support the hypothesis that ABCB1 and possibly other ABC
      transporters are involved in the process of Abeta accumulation in the aging brain
      and may modulate the risk for AD in an allele-specific manner, and thus might
      represent a new target for prevention and treatment of AD.

PMID- 23556447
TI  - Genes involved in hemorrhagic transformations that follow recombinant t-PA
      treatment in stroke patients.
AB  - AIM: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of
      them suffer from adverse hemorrhagic transformations (HTs) following treatment.
      Our objective is to study the transcriptomics of HTs patients. METHODS: We
      studied by microarrays 11 blood samples from patients with stroke that had
      received rt-PA of whom six of them had suffered a HT. For replication step RNA
      was collected from 14 new subjects (seven with HT, seven without) and then
      analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new
      subjects to analyze their role as potential protein biomarkers. RESULTS: The
      microarray analysis revealed that 14 genes were altered among the HT patients.
      The replication study confirmed these results for six genes. Two of them (BCL2
      and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also
      known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil
      processes. CONCLUSION: Our data revealed that genes related to apoptosis and
      neutrophil regulation pathways could be associated with HTs after rt-PA.

PMID- 23556448
TI  - Association of a functional FAAH polymorphism with methamphetamine-induced
      symptoms and dependence in a Malaysian population.
AB  - AIM: FAAH is a membrane enzyme that terminates the activity of a large class of
      endogenous signaling lipids. Recent studies suggest that the FAAH Pro129Thr
      polymorphism is a common mutation in the FAAH gene that is significantly
      associated with drug-addictive traits. This study investigated the association of
      the Pro129Thr polymorphism of the FAAH gene with methamphetamine dependence,
      methamphetamine-induced psychosis, manic episodes and panic disorder in a
      Malaysian population. MATERIALS & METHODS: This polymorphism was genotyped in 232
      male methamphetamine-dependent subjects and in 241 male controls of four
      different ethnicities: Malay, Chinese, Kadazan-Dusun and Bajau. Intergroup
      statistical analyses were performed by using the chi(2)-square test and Fisher's
      exact test, where necessary. In cases of multiple comparisons, the Bonferroni
      correction was performed. RESULTS: Our results indicated that the FAAH Pro129Thr
      polymorphism showed a significant association with risk of methamphetamine
      dependence in the pooled subjects (odds ratio [OR]: 2.017; p < 0.001) and in the
      Malay (OR: 2.829; p < 0.001) and Chinese (OR: 3.685; p < 0.001) groups. We also
      found an association of this polymorphism with episodes of methamphetamine
      induced mania in the Malay group (OR: 2.836; p = 0.035). However, there was no
      association between this polymorphism and age of onset of drug use or the
      occurrence of methamphetamine-induced psychosis or of panic disorder. CONCLUSION:
      Our findings suggest that the FAAH Pro129Thr polymorphism may contribute to
      methamphetamine dependence in the Malay and Chinese ethnic groups.

PMID- 23556449
TI  - The expression profile of ATP-binding cassette transporter genes in breast
      carcinoma.
AB  - AIM: ATP-binding cassette (ABC) transporters contribute to development of
      resistance to anticancer drugs via ATP-dependent drug efflux. A major goal of our
      study was to investigate associations between the expression of ABC transporters
      and outcome of breast carcinoma patients. PATIENTS & METHODS: Transcript levels
      of all 49 human ABC transporters were determined in post-treatment tumor and non
      neoplastic tissue samples from 68 breast carcinoma patients treated by
      neoadjuvant chemotherapy. Six ABC transporters were then evaluated in independent
      series of 100 pretreatment patients. RESULTS: ABCA5/6/8/9/10, ABCB1/5/11,
      ABCC6/9, ABCD2/4, ABCG5 and ABCG8 were significantly downregulated and
      ABCA2/3/7/12, ABCB2/3/8/9/10, ABCC1/4/5/10/11/12, ABCD1/3, ABCE1, ABCF1/2/3 and
      ABCG1 were upregulated in post-treatment tumors compared with non-neoplastic
      tissues. Significant associations of intratumoral levels of ABCC1 and ABCC8 with
      grade and expression of hormonal receptors were found in both sets of patients.
      ABCA12, ABCA13 and ABCD2 levels were significantly associated with the response
      to neoadjuvant chemotherapy in post-treatment patients. Protein expression of
      ABCA12, ABCC8 and ABCD2 in tumor tissues of patients with breast carcinoma was
      observed by immunoblotting for the first time. CONCLUSION: ABCA12, ABCA13, ABCC1,
      ABCC8 and ABCD2 present potential modifiers of progression and response to the
      chemotherapy of breast carcinoma.

PMID- 23556450
TI  - HLA-DRB1*1501 and VDR polymorphisms and survival of Mycobacterium tuberculosis in
      human macrophages exposed to inhalable microparticles.
AB  - AIM: We examined whether HLA-DRB1*1501 and four VDR SNPs influence the macrophage
      response to infection with Mycobacterium tuberculosis (Mtb) via innate immune
      versus drug treatment or drug delivery mechanisms. MATERIALS & METHODS: Monocyte
      derived macrophages from 24 healthy donors were infected with Mtb in vitro.
      Survival of intracellular bacilli and secretion of cytokines and nitric oxide by
      the infected cells were monitored with and without exposure to isoniazid and
      rifabutin. RESULTS: Haplotype analysis was conducted, and an arbitrary score of
      genetic 'susceptibility' (S ) score ranging from -3 to +3 was assigned to donors
      based on the presence or absence of genetic markers. S scores correlated more
      strongly with Mtb survival (r = 0.68) than TNF and nitric oxide (NO; r = ~0.01
      0.11). A specific haplotype was significantly associated with decreased Mtb
      survival (p < 0.05), increased NO and decreased IL-10/IL-4. Macrophages with S
      scores >= 2 secreted significantly (p < 0.05) more IL-10 and IL-4, and less NO
      upon infection, and supported Mtb survival. Microparticulate drugs showed higher
      bactericidal activity than free drugs, irrespective of S score. CONCLUSION: S
      score predicts colonization of macrophages by Mtb, as does haplotype analysis.
      Drug-containing microparticles are superior to free drugs across diverse genetic
      backgrounds.

PMID- 23556451
TI  - Genetic characterization to improve interpretation and clinical management of
      hepatotoxicity caused by tyrosine kinase inhibitors.
AB  - Tyrosine kinase inhibitors (TKIs) represent important therapeutic alternatives
      to, or combinations with, traditional cytotoxic chemotherapy. Despite their
      selective molecular targeting and demonstrated clinical benefit, TKIs produce a
      range of serious adverse events, including drug-induced liver injury, that
      require careful patient management to maintain treatment benefit without harm.
      Genetic characterization of serious adverse events can identify mechanisms of
      injury and improve safety risk management. This review presents pharmacogenetic
      comparisons of two approved TKIs, lapatinib and pazopanib, which reveal different
      mechanisms of injury and inform the characteristics and risk of serious liver
      injury in treated patients. The data presented demonstrate the utility of genetic
      studies to investigate drug-induced liver injury and potentially support its
      management in patients.

PMID- 23556453
TI  - Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg.
AB  - Opioids are the cornerstone of analgesic therapy and are used as a substitution
      therapy for opiate addiction. Interindividual variability in response to opioids
      is a significant challenge in the management of pain and substitution. Therefore,
      treatment with opioids requires a careful individualization of dosage to achieve
      an appropriate balance of efficacy and adverse effects and, consequently, avoid
      toxicity, particularly respiratory depression, sedation and for some, cardiac
      ventricular fibrillations. Many studies have investigated the association between
      genetic factors and the variability of response to opioids. Variants in genes
      encoding proteins implied in opioid pharmacokinetics (absorption, distribution,
      metabolism, excretion and toxicity), together with those implied in opioids
      direct and indirect pharmacodynamics (genes of opioid receptors and monoaminergic
      systems), are the most studied. Many association studies have not been
      replicated. The purpose of this article is to summarize pharmacogenetic data
      associated with some opioids frequently encountered in managed care settings.

PMID- 23556452
TI  - Pharmacogenetics, enzyme probes and therapeutic drug monitoring as potential
      tools for individualizing taxane therapy.
AB  - The taxanes are a class of chemotherapeutic agents that are widely used in the
      treatment of various solid tumors. Although taxanes are highly effective in
      cancer treatment, their use is associated with serious complications attributable
      to large interindividual variability in pharmacokinetics and a narrow therapeutic
      window. Unpredictable toxicity occurrence necessitates close patient monitoring
      while on therapy and adverse effects frequently require decreasing, delaying or
      even discontinuing taxane treatment. Currently, taxane dosing is based primarily
      on body surface area, ignoring other factors that are known to dictate
      variability in pharmacokinetics or outcome. This article discusses three
      potential strategies for individualizing taxane treatment based on patient
      information that can be collected before or during care. The clinical
      implementation of pharmacogenetics, enzyme probes or therapeutic drug monitoring
      could enable clinicians to personalize taxane treatment to enhance efficacy
      and/or limit toxicity.

PMID- 23556455
TI  - Characterization of casein hydrolysates derived from enzymatic hydrolysis.
AB  - BACKGROUND: Casein is the main proteinaceous component of milk and has made us
      interest due to its wide applications in the food, drug, and cosmetic industries
      as well as to its importance as an investigation material for elucidating
      essential questions regarding the protein chemistry. Enzymatic hydrolysis is an
      important method commonly used in the modification of protein structure in order
      to enhance the functional properties of proteins. The relationship between
      enzymatic hydrolysis and structure change of casein need to make more study.
      RESULTS: During hydrolysis, degree of hydrolysis in the casein hydrolysates
      increased rapidly in the initial 20 minutes, reached a plateau after 45 minutes,
      and then kept relative constant for the rest of the hydrolysis. The relative
      percentage of the released peptides with molecular weight of over 50 kD
      significantly decreased with hydrolyzation, while those with MW of 30-50 kD and
      below 20 kD increased significantly. The contents of a-helix and beta-turn in the
      hydrolysates increased compared to the original casein. Moreover, the molecular
      flexibilities of the casein hydrolysates, estimated by the ratio of alpha-helix
      to beta-structure, were lower than that of original casein protein. CONCLUSIONS:
      The significant changes in molecular weight distribution and structure
      characteristics of casein hydrolysates were found compared to the control sample.
      This change should be the basis of enhancement of functional properties.

PMID- 23556456
TI  - Molecular characterization of Tunisian families with abetalipoproteinemia and
      identification of a novel mutation in MTTP gene.
AB  - BACKGROUND: Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder
      of lipid metabolism characterized by reduced plasma levels of total cholesterol
      (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of
      apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal
      triglyceride transfer protein (MTP; OMIM 157147). In the present study we
      investigated two unrelated Tunisian patients, born from consanguineous marriages,
      with severe deficiency of plasma low-density lipoprotein (LDL) and apo B.
      METHODS: Intestinal biopsies were performed and The MTTP gene was amplified by
      Polymerase chain reaction then directly sequenced in patients presenting chronic
      diarrhea and retarded growth. RESULTS: First proband was homozygous for a novel
      nucleotide deletion (c. 2611delC) involving the exon 18 of MTTP gene predicted to
      cause a non functional protein of 898 amino acids (p.H871I fsX29). Second proband
      was homozygous for a nonsense mutation in exon 8 (c.923 G > A) predicted to cause
      a truncated protein of 307 amino acids (p.W308X), previously reported in ABL
      patients. CONCLUSIONS: We discovered a novel mutation in MTTP gene and we
      confirmed the diagnosis of abetalipoproteinemia in new Tunisian families. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/8134027928652779.

PMID- 23556458
TI  - Macrophage migration inhibitory factor promoter 173G/C polymorphism is associated
      with atopic dermatitis risk.

PMID- 23556457
TI  - Postsynaptic kainate receptor recycling and surface expression are regulated by
      metabotropic autoreceptor signalling.
AB  - Kainate receptors (KARs) play fundamentally important roles in controlling
      synaptic function and regulating neuronal excitability. Postsynaptic KARs
      contribute to excitatory neurotransmission but the molecular mechanisms
      underlying their activity-dependent surface expression are not well understood.
      Strong activation of KARs in cultured hippocampal neurons leads to the
      downregulation of postsynaptic KARs via endocytosis and degradation. In contrast,
      low-level activation augments postsynaptic KAR surface expression. Here, we show
      that this increase in KARs is due to enhanced recycling via the recruitment of
      Rab11-dependent, transferrin-positive endosomes into spines. Dominant-negative
      Rab11 or the recycling inhibitor primaquine prevents the kainate-evoked increase
      in surface KARs. Moreover, we show that the increase in surface expression is
      mediated via a metabotropic KAR signalling pathway, which is blocked by the
      protein kinase C inhibitor chelerythrine, the calcium chelator BAPTA and the G
      protein inhibitor pertussis toxin. Thus, we report a previously uncharacterized
      positive feedback system that increases postsynaptic KARs in response to low- or
      moderate-level agonist activation and can provide additional flexibility to
      synaptic regulation.

PMID- 23556462
TI  - The end of the beginning.

PMID- 23556461
TI  - Quantitation of hydrogen peroxide fluctuations and their modulation of dopamine
      dynamics in the rat dorsal striatum using fast-scan cyclic voltammetry.
AB  - The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the
      substantia nigra to the dorsal striatum become dysfunctional and slowly
      degenerate in Parkinson's disease, a neurodegenerative disorder that afflicts
      more than one million Americans. There is no specific known cause for idiopathic
      Parkinson's disease; however, multiple lines of evidence implicate oxidative
      stress as an underlying factor in both the initiation and progression of the
      disease. This involves the enhanced generation of reactive oxygen species,
      including hydrogen peroxide (H2O2), whose role in complex biological processes is
      not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber
      microelectrodes, we have simultaneously monitored and quantified H2O2 and DA
      fluctuations in intact striatal tissue under basal conditions and in response to
      the initiation of oxidative stress. Furthermore, we have assessed the effect of
      acute increases in local H2O2 concentration on both electrically evoked DA
      release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum
      attenuated electrically evoked DA release, and also decreased basal DA levels in
      this brain region. These novel results will help to disambiguate the chemical
      mechanisms underlying the progression of neurodegenerative disease states, such
      as Parkinson's disease, that involve oxidative stress. 

PMID- 23556460
TI  - In vitro degradation and fermentation of three dietary fiber sources by human
      colonic bacteria.
AB  - Although clinical benefits of dietary fiber supplementation seem to depend
      partially on the extent of fiber degradation and fermentation by colonic
      bacteria, little is known about the effect of supplemental fiber type on
      bacterial metabolism. In an experiment using a nonadapted human bacterial
      population from three normal subjects, the extent of in vitro fermentation was
      greater for gum arabic (GA) than for psyllium (PSY), which was greater than that
      for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation
      with feces from 52 subjects with fecal incontinence, before and after random
      assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements
      or a placebo for 20-21 days, indicated that prior consumption of a specific fiber
      source did not increase its degradation by fecal bacteria. Results suggest that
      the colonic microbial community enriched on a particular fiber substrate can
      rapidly adapt to the presentation of a new fiber substrate. Clinical implications
      of the findings are that intake of a fiber source by humans is not expected to
      result in bacterial adaptation that would require continually larger and
      eventually intolerable amounts of fiber to achieve therapeutic benefits.

PMID- 23556459
TI  - Plasma neutrophil gelatinase-associated lipocalin and adverse outcome in
      critically ill patients with ventilatory support.
AB  - OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been
      introduced as an early and sensitive biomarker of acute kidney injury (AKI), with
      an increased risk for renal replacement therapy (RRT) and adverse outcome in
      selected critically ill patient groups. Acute respiratory failure is the most
      common organ dysfunction in critically ill patients with an increased risk for
      AKI. Accordingly, we hypothesized that pNGAL would independently predict adverse
      outcome in a heterogeneous group of critically ill adult patients with acute
      respiratory failure. DESIGN AND SETTING: Prospective, multi-centre study in 25
      Finnish intensive care units. PATIENTS AND METHODS: pNGAL was measured from
      critically ill patients with acute respiratory failure. We evaluated the
      predictive value of pNGAL for RRT, and hospital and 90-day mortality first
      separately, second in addition to the Simplified Acute Physiology Score (SAPS
      II), and third to RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease)
      AKI classification. Additionally, we assessed the factors associated with pNGAL
      by linear regression analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: We included 369 patients. Median (interquartile range) baseline pNGAL
      was 169 (92-370) ng/ml. The areas under receiver operating characteristic curves
      of baseline pNGAL were as follows: 0.733 [95% confidence interval (CI) 0.656
      0.810] for RRT, 0.627 (95% CI 0.561-0.693) for hospital, and 0.582 (95% CI 0.520
      0.645) for 90-day mortality. Present infection, baseline creatinine, operative
      status, and pancreatitis were independently associated with baseline pNGAL.
      CONCLUSIONS: Baseline pNGAL gives no additional value into prediction of hospital
      and 90-day mortality compared with RIFLE or SAPS II, and has only moderate
      predictive power regarding RRT in critically ill adult patients with acute
      respiratory failure.

PMID- 23556463
TI  - Welcome to the ninth international conference on pediatric mechanical circulatory
      support systems and pediatric cardiopulmonary perfusion.

PMID- 23556467
TI  - Ridge preservation with the use of deproteinized bovine bone mineral.
AB  - OBJECTIVE: The aim was to examine the tissue composition of extraction sockets
      that had been grafted with deproteinized bovine bone mineral and allowed to heal
      for 6 months. MATERIAL AND METHODS: Twenty-five subjects with one tooth each
      scheduled for extraction and replacement with dental implants were recruited. The
      assigned teeth were carefully removed. The site/patient was thereafter allocated
      to a test or a control group. In the test group patients, Bio-Oss((r)) Collagen
      was placed to fill the fresh extraction socket while in the controls no grafting
      was performed. After about 6 months of healing, a biopsy was sampled from the
      center of the extraction site. The specimens were decalcified, embedded in
      paraffin, sectioned, and stained in HTX. The proportions occupied by mineralized
      bone, osteoid, bone marrow, fibrous tissue, and Bio-Oss((r)) particles were
      determined by morphometric point counting. RESULTS: Mineralized bone made up 57.4
      +/- 12.4% of the control sites (C) and 48.9 +/- 8.5% of the T1 sites (graft
      material not included). The amount of bone marrow (C: 7.1 +/- 6.1%, T1: 2.1 +/-
      3.1%) and osteoid (C: 7.3 +/- 4.9%, T1: 1.9 +/- 2.1%) was about five times
      greater in the control than in the test sites. Fibrous tissue comprised 23.1 +/-
      16.3% (C) and 40.0 +/- 11.9% (T1). I n the T2 sites (graft material included),
      the percentage mineralized bone was 39.9 +/- 8.6 while the proportions of bone
      marrow and osteoid were 1.8 +/- 2.5% and 1.6 +/- 1.8%. Fibrous tissue occupied
      32.4 +/- 9.2% and Bio-Oss((r)) particles 19.0 +/- 6.5% of the T2 sites.
      CONCLUSION: Placement of the biomaterial in the fresh extraction socket retarded
      healing. The Bio-Oss((r)) particles were not resorbed but became surrounded by
      new bone. This may explain why grafted extraction sites may fail to undergo
      dimensional change.

PMID- 23556468
TI  - NANDA-I with NIC NOC'n on heaven's door.

PMID- 23556466
TI  - Early prenatal food supplementation ameliorates the negative association of
      maternal stress with birth size in a randomised trial.
AB  - Low birthweight increases the risk of infant mortality, morbidity and poor
      development. Maternal nutrition and stress influence birth size, but their
      combined effect is not known. We hypothesised that an early-invitation time to
      start a prenatal food supplementation programme could reduce the negative
      influence of prenatal maternal stress on birth size, and that effect would differ
      by infant sex. A cohort of 1041 pregnant women, who had delivered an infant, June
      2003-March 2004, was sampled from among 3267 in the randomised controlled trial,
      Maternal Infant Nutritional Interventions Matlab, conducted in Matlab,
      Bangladesh. At 8 weeks gestation, women were randomly assigned an invitation to
      start food supplements (2.5 MJ d(-1) ; 6 days a week) either early (~9 weeks
      gestation; early-invitation group) or at usual start time for the governmental
      programme (~20 weeks gestation; usual-invitation group). Morning concentration of
      cortisol was measured from one saliva sample/woman at 28-32 weeks gestation to
      assess stress. Birth-size measurements for 90% of infants were collected within 4
      days of birth. In a general linear model, there was an interaction between
      invitation time to start the food supplementation programme and cortisol with
      birthweight, length and head circumference of male infants, but not female
      infants. Among the usual-invitation group only, male infants whose mothers had
      higher prenatal cortisol weighed less than those whose mothers had lower prenatal
      cortisol. Prenatal food supplementation programmes that begin first trimester may
      support greater birth size of male infants despite high maternal stress where low
      birthweight is a public health concern. 

PMID- 23556469
TI  - Suction purpura in humans caused by octopus arms.

PMID- 23556470
TI  - The thermal voltage fluctuations in the planar core-coat conductor of a neuron
      semiconductor interface.
AB  - The extracellular electrical interfacing of nerve cells with metals or
      semiconductors is governed by the resistance of the cell-solid junction. With
      snail neurons on a CMOS chip, we have probed the thermal voltage fluctuations in
      the junction at a spatial resolution of 7.4 MUm in a spectral range from 10 Hz to
      1 MHz using an array of sensor transistors. The power spectral density (PSD)
      could be interpreted in terms of a Johnson-Nyquist noise if the distributed
      nature of the cell-solid junction and the size of the sensors were taken into
      account. The PSD over the whole spectral range as well as its spatial profile
      were matched by the thermal noise of a circular core-coat conductor with a
      homogeneous sheet resistance in the range of 100 MOmega. The quantitative
      interpretation of the thermal noise in a cell-solid junction provides a basis for
      applications of this noninvasive method in the characterization of biosensoric
      and neuroprosthetic devices.

PMID- 23556471
TI  - Regional differences in diabetes prevalence and awareness between coastal and
      interior provinces in China: a population-based cross-sectional study.
AB  - BACKGROUND: Most studies on diabetes prevalence and awareness in China are
      regional or about a single province, and differences between coastal and interior
      provinces have not been discussed even in the nation-based studies. The aim of
      this study was to determine regional differences in diabetes prevalence and
      awareness between coastal and interior provinces, and to identify the factors
      associated with diabetes prevalence and awareness. METHODS: Provinces Fujian and
      Shaanxi were chosen to represent the coastal and interior provinces,
      respectively. The data of two provinces were from the China National Diabetes and
      Metabolic Disorders Study 2007-08. A total of 5926 people (Fujian 2672 and
      Shaanxi 3254) aged above 20 years were included as participants in the study. Age
      standardized prevalence and awareness were compared between provinces. Logistic
      regression analysis was performed not only to examine risk factors of diabetes
      prevalence and awareness, but also to examine the association between regional
      difference and diabetes prevalence and awareness. RESULTS: The age-standardized
      prevalence of diabetes in Fujian was higher than that in Shaanxi among total
      (11.5% vs. 8.0%), male (13.6% vs. 8.9%) and female (10.8% vs. 7.4%) populations.
      Diabetes awareness for total and male population in Fujian was higher than that
      in Shaanxi (42.3% vs. 34.9% and 46.8% vs. 35.2%, respectively). Age, sex, central
      obesity, family history of diabetes, and metabolic risk factors were all
      significantly associated with diabetes prevalence in both provinces. However,
      cigarette smoking was significantly associated with prevalence in Fujian and
      physical activity was significantly associated with the prevalence in Shaanxi.
      Family history of diabetes was the only independent risk factor of diabetes
      awareness in both provinces. After being adjusted for all listed risk factors,
      the regional difference of diabetes prevalence was still significant, but that of
      diabetes awareness lost significance. CONCLUSIONS: Both diabetes prevalence and
      awareness were higher in coastal provinces and lower in interior provinces in
      China. Lifestyle risk factors were found to contribute differently to diabetes
      prevalence in the two provinces and other unknown risk factors may account for
      differences of diabetes prevalence between provinces. In addition, family history
      of diabetes was the only independent risk factor in both provinces.

PMID- 23556472
TI  - Intracranial haemorrhage in von Willebrand disease: a report on six cases.
AB  - The incidence of intracranial haemorrhage (ICH) in von Willebrand disease (VWD)
      is not well documented. We describe our single centre experience regarding ICH in
      children with VWD and identify how such children presented and were managed.
      Thirty-three head trauma events leading to medical attention occurred in 24 of
      153 children with VWD followed in our institution. In only 15 of these were
      computed tomography (CT) imaging studies performed; seven in children with type 1
      VWD, one in a child with type 2N VWD and seven in children with type 3 VWD. In
      six of these 15 episodes an ICH was identified: two children with type 1 VWD, one
      child with type 2N VWD and three children with type 3 VWD. In two of the 6 cases
      an ICH was only confirmed following a second CT scan. Neurological symptoms,
      including vomiting (noted in all six), headache, irritability, lethargy and/or
      alteration in the level of consciousness were present in all children with
      confirmed ICH. In contrast vomiting, irritability and alterations in level of
      consciousness were never present in those children without confirmed ICH. All
      three children with type 3 VWD who experienced an ICH were commenced on long-term
      prophylaxis. ICH, although rare, does occur in children with VWD and particularly
      in children with type 3 VWD. A much larger cohort of patients with VWD
      experiencing an ICH is needed to make recommendations regarding treatment of such
      events, including the role of prophylaxis in patients with more severe forms of
      VWD.

PMID- 23556475
TI  - Influence of the metal (Al, Cr, and Co) and substituents of the porphyrin in
      controlling reactions involved in copolymerization of propylene oxide and carbon
      dioxide by porphyrin metal(III) complexes. 3. Cobalt chemistry.
AB  - A series of cobalt(III) complexes LCoX, where L = 5,10,15,20-tetraphenylporphyrin
      (TPP), 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TFPP), and
      2,3,7,8,12,13,17,18-octaethylporphyirn (OEP) and X = Cl or acetate, has been
      investigated for homopolymerization of propylene oxide (PO) and copolymerization
      of PO and CO2 to yield polypropylene oxide (PPO) and polypropylene carbonate
      (PPC) or propylene carbonate (PC), respectively. These reactions were carried out
      both with and without the presence of a cocatalyst, namely, 4
      dimethylaminopyridine (DMAP) or PPN(+)Cl(-) (bis(triphenylphosphine)iminium
      chloride). The PO/CO2 copolymerization process is notably faster than PO
      homopolymerization. With ionic PPN(+)Cl(-) cocatalyst the TPPCoOAc catalyst
      system grows two chains per Co center and the presence of excess [Cl(-)]
      facilitates formation of PC by two different backbiting mechanisms during
      copolymerization. Formation of PPC is dependent on both [Cl(-)] and the CO2
      pressure employed (1-50 bar). TPPCoCl and PO react to form TPPCo(II) and
      ClCH2CH(Me)OH, while with DMAP, TPPCoCl yields TPPCo(DMAP)2(+)Cl(-). The
      reactions and their polymers and other products have been monitored by various
      methods including react-IR, FT-IR, GPC, ESI, MALDI TOF, EXAFS, and NMR ((1)H,
      (13)C{(1)H}) spectroscopy. Notable differences are seen in these reactions with
      previous studies of (porphyrin)M(III) complexes (M = Al, Cr) and of the
      (salen)M(III) complexes where M = Cr, Co.

PMID- 23556473
TI  - Identification of vancomycin-resistant enterococci clones and inter-hospital
      spread during an outbreak in Taiwan.
AB  - BACKGROUND: In 2003, nosocomial infections caused by vancomycin-resistant
      enterococci (VRE) occurred rarely in Taiwan. Between 2003 and 2010, however, the
      average prevalence of vancomycin resistance among enterococci spp. increased from
      2% to 16% in community hospitals and from 3% to 21% in medical centers of Taiwan.
      We used molecular methods to investigate the epidemiology of VRE in a tertiary
      teaching hospital in Taiwan. METHODS: Between February 2009 and February 2011,
      rectal samples and infection site specimens were collected from all inpatients in
      the nephrology ward after patient consent was obtained. VRE strain types were
      determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence
      typing (MLST). RESULTS: A total of 59 vanA gene-containing VRE isolates (1 per
      patient) were obtained; 24 originated from rectal sample surveillance of patients
      who exhibited no symptoms (22 Enterococcus faecium and 2 Enterococcus faecalis),
      and 35 had developed infections over 3 days after admission (32 E. faecium, 2 E.
      faecalis, and 1 Enterococcus durans). The 59 VRE isolates demonstrated vancomycin
      minimum inhibitory concentrations (MICs) of >=256 MUg/m. The MIC range for
      linezolid, tigecycline, and daptomycin was 0.25-1.5 MUg/mL, 0.032-0.25 and 1-4
      MUg/mL, respectively. For 56 isolates, the MIC for teicoplanin was >8 MUg/mL. The
      predominant types in the nephrology ward were MLST types 414, 78, and18 as well
      as PFGE types A, C, and D. CONCLUSION: VREs are endemic in nephrology wards. MLST
      414 is the most predominant strain. The increase VRE prevalence is due to cross
      transmission of VRE clones ST 414,78,18 by undetected VRE carriers. Because
      similar VRE STs had been reported in a different hospital of Taiwan, this finding
      may indicate inter-hospital VRE spread in Taiwan. Active surveillance and
      effective infection control policies are important controlling the spread of VRE
      in high risk hospital zones. All endemic VRE strains are resistant to teicoplanin
      but are sensitive to daptomycin, linezolid, and tigecycline.

PMID- 23556474
TI  - Evaluation of effects of copper histidine on copper transporter 1-mediated
      accumulation of platinum and oxaliplatin-induced neurotoxicity in vitro and in
      vivo.
AB  - The purpose of the present study was to determine whether copper histidine could
      inhibit copper transporter 1 (Ctr1)-mediated transport of oxaliplatin in vitro
      and thereby limit the accumulation of platinum and neurotoxicity of oxaliplatin
      in dorsal root ganglion (DRG) tissue in vivo. In HEK293 cells overexpressing rat
      Ctr1, copper histidine was shown to be transported by Ctr1 and to inhibit their
      Ctr1-mediated uptake of oxaliplatin. Pilot in vivo dose-finding studies showed
      that copper histidine at doses up to 2 mg/kg, p.o., daily for 5 days/week could
      be added to maximum tolerated doses of oxaliplatin (1.85 mg/kg, i.p., twice
      weekly) for 8 week combination treatment studies in female Wistar rats. After
      treatment, rats showed significant changes in sensory neuron size profiles in DRG
      tissue induced by oxaliplatin that were not altered by its coadministration with
      copper histidine. The expression of copper transporters (Ctr1 and copper
      transporting P-type ATPase 1 (Atp7a)) in DRG tissue appeared unchanged following
      treatment with oxaliplatin given alone or with copper histidine. Platinum and
      copper tissue levels were higher in DRG than in most other tissues, but were
      unaltered by the addition of copper histidine to oxaliplatin treatment. In
      conclusion, copper histidine inhibited cellular uptake of oxaliplatin mediated by
      Ctr1 in vitro without altering the accumulation of platinum or neurotoxicity of
      oxaliplatin in DRG tissue in vivo at doses tolerated in combination with
      oxaliplatin treatment.

PMID- 23556476
TI  - Asymmetric synthesis of (-)-martinellic acid.
AB  - A high-yielding total asymmetric synthesis of (-)-martinellic acid is reported.
      The conjugate addition of lithium (R)-N-allyl-N-(alpha-methyl-4
      methoxybenzyl)amide to tert-butyl (E)-3-[2'-(N,N-diallylamino)-5'
      bromophenyl]propenoate and alkylation of the resultant beta-amino ester have been
      used as the key steps to install the C(9b) and C(3a) stereogenic centers,
      respectively, and a highly diastereoselective Wittig reaction/intramolecular
      Michael addition was then used to create the C(4) stereogenic center within this
      tricyclic molecular architecture.

PMID- 23556479
TI  - Graves' immune reconstitution inflammatory syndrome in childhood.
AB  - BACKGROUND: The use of hematopoietic stem cell transplantations (HSCTs) as a
      curative therapy for life-threatening immunodeficiencies has had a profound
      impact on clinical outcomes. A subset of patients may experience immune
      reconstitution inflammatory syndrome (IRIS) post-transplant affecting the thyroid
      gland, but this has received little attention in the pediatric literature. We
      present the clinical, biochemical, and cytological course of patients with
      Graves' disease after HSCT in the pediatric population. PATIENTS AND METHODS:
      Four children (median age 1.5 years, range 2 months-9 years) underwent HSCT. The
      conditioning regimen included chemotherapy but not radiotherapy. None of the
      children or their donors had evidence of thyroid disease pre-HSCT or during the
      follow-up period. Engraftment was uneventful in all, with stable donor T-cell
      chimerism, and none had evidence of graft-versus-host disease. RESULTS: Patients
      developed Graves' disease soon after undergoing HSCT, with a median time interval
      between HSCT and Graves' disease of 22 months (range 16-28 months). Graves'
      disease was diagnosed on the basis of clinical and biochemical parameters,
      including a suppressed thyrotropin, raised free thyroxine, and raised thyrotropin
      receptor antibodies. Three patients were hypothyroid initially (suggestive of a
      Th1 profile) before Graves' disease (suggestive of a Th2 profile). In three
      patients, the clinical picture changed rapidly with hypothyroidism abruptly
      followed by profound thyroid hormone excess. The onset of Graves' IRIS coincided
      with a rapid expansion in naive and total CD4. CONCLUSIONS: Immunological
      dysregulation during T-cell engraftment is the most likely mechanism for
      developing Graves' IRIS after allogenic HSTC. Clinicians need to be aware that
      HSCT-engendered immune recovery may result in a particularly aggressive form of
      autoimmune thyroid disease in children with implications for the developing
      central nervous system. Careful surveillance of thyroid function post-HSCT is
      essential.

PMID- 23556480
TI  - On the condensed phase ring-closure of vinylheptafulvalene and ring-opening of
      gaseous dihydroazulene.
AB  - Dihydroazulenes are interesting because of their photoswitching behavior. While
      the ring-opening to vinylheptafulvalene (VHF) is light induced, the back reaction
      is known to proceed thermally. In the present paper, we show the first gas phase
      study of the ring-opening reaction of 2-phenyl-1,8a-dihydroazulene-1,1
      dicarbonitrile (Ph-DHA) by means of time-resolved photoelectron spectroscopy
      which permits us to follow the ring-opening process. Moreover, we investigated s
      trans-Ph-VHF in a series of transient absorption experiments, supported by ab
      initio computations, to understand the origin of the absence of light-induced
      ring-closure. The transient absorption results show a biexponential decay
      governed by a hitherto unknown state. This state is accessed within 1-2 ps and
      return to the ground state is probably driven through a cis-trans isomerization
      about the exocyclic C1?C2 double bond. The rapid decrease in potential energy
      disfavors internal rotation to s-cis-Ph-VHF, the structure that would precede the
      ring-closure reaction.

PMID- 23556478
TI  - Absolute copy number differences of Y chromosomal genes between crossbred (Bos
      taurus * Bos indicus) and Indicine bulls.
AB  - BACKGROUND: The Y chromosome in mammal is paternally inherited and harbors genes
      related to male fertility and spermatogenesis. The unique intra-chromosomal
      recombination pattern of Y chromosome and morphological difference of this
      chromosome between Bos taurus and Bos indicus make it an ideal model for studying
      structural variation, especially in crossbred (Bos taurus * Bos indicus) bulls.
      Copy Number Variation (CNV) is a type of genomic structural variation that gives
      information complementary to SNP data. The purpose of this study was to find out
      copy number differences of four Y chromosomal spermatogenesis-related candidate
      genes in genomic DNA of crossbred and purebred Indicine bulls. RESULT: Four Y
      chromosomal candidate genes of spermatogenesis namely, sex determining gene on Y
      chromosome (SRY), DEAD box polypeptide 3-Y chromosome (DDX3Y), Ubiquitin specific
      peptidase 9, Y-linked (USP9Y), testis-specific protein on Y chromosome (TSPY)
      were evaluated. Absolute copy numbers of Y chromosomal genes were determined by
      standard curve-based quantitative real time PCR. Copy numbers of SRY and TSPY
      genes per unit amount of genomic DNA are higher in crossbred than Indicine bulls.
      However, no difference was observed in DDX3Y and USP9Y gene copy numbers between
      two groups. CONCLUSION: The present study demonstrates that the structural
      organization of Y chromosomes differs between crossbred and Indicine bulls which
      are reproductively healthy as observed from analysis of semen attributes. The
      absolute copy numbers of SRY and TSPY genes in unit mass of genomic DNA of
      crossbred bulls are significantly higher than Indicine bulls. No alteration in
      absolute copies of DDX3Y and USP9Y gene was found between the genome of crossbred
      and Indicine bulls. This study suggests that the DDX3Y and USP9Y are likely to be
      single copy genes in the genome of crossbred and Indicine bulls and variation in
      Y chromosome length between crossbred and Indicine bulls may be due to the copy
      number variation of SRY gene and TSPY array.

PMID- 23556477
TI  - 1H-NMR based metabonomic profiling of human esophageal cancer tissue.
AB  - BACKGROUND: The biomarker identification of human esophageal cancer is critical
      for its early diagnosis and therapeutic approaches that will significantly
      improve patient survival. Specially, those that involves in progression of
      disease would be helpful to mechanism research. METHODS: In the present study, we
      investigated the distinguishing metabolites in human esophageal cancer tissues (n
      = 89) and normal esophageal mucosae (n = 26) using a (1)H nuclear magnetic
      resonance ((1)H-NMR) based assay, which is a highly sensitive and non-destructive
      method for biomarker identification in biological systems. Principal component
      analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and
      orthogonal partial least-squares-discriminant analysis (OPLS-DA) were applied to
      analyse (1)H-NMR profiling data to identify potential biomarkers. RESULTS: The
      constructed OPLS-DA model achieved an excellent separation of the esophageal
      cancer tissues and normal mucosae. Excellent separation was obtained between the
      different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and
      stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and
      12 of them were closely correlated with the stage of esophageal cancer. The
      downregulation of glucose, AMP and NAD, upregulation of formate indicated the
      large energy requirement due to accelerated cell proliferation in esophageal
      cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal
      cancer tissue revealed the activation of fatty acids metabolism, which could
      satisfy the need for cellular membrane formation. Other modified metabolites were
      involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA
      and TMA. These 12 metabolites, which are involved in energy, fatty acids and
      choline metabolism, may be associated with the progression of human esophageal
      cancer. CONCLUSION: Our findings firstly identify the distinguishing metabolites
      in different stages of esophageal cancer tissues, indicating the attribution of
      metabolites disturbance to the progression of esophageal cancer. The potential
      biomarkers provide a promising molecular diagnostic approach for clinical
      diagnosis of human esophageal cancer and a new direction for the mechanism study.

PMID- 23556481
TI  - Discoveries in the pathophysiology of neuropsychiatric lupus erythematosus:
      consequences for therapy.
AB  - Systemic lupus erythematosus (SLE) is a multi-system inflammatory disorder
      characterized by the presence of several autoantibodies, including anti-double
      stranded DNA. Neuropsychiatric (NP)LE contributes to the prognosis of SLE, and is
      divided into 19 NPLE syndromes. Its mechanisms are mediated through
      autoantibodies, complement components, and cytokines. The pathophysiology and
      diagnosis of NPLE are diverse and complicated. Recent studies have shown that
      several autoantibodies cross-react with human brain tissue and cause NPLE
      symptoms in SLE. It is known that in mice, depression and hippocampus-related
      memory impairment are induced by anti-ribosomal P antibody and anti-NR2 antibody,
      respectively. In a BMC Medicine research article, Kivity et al. demonstrated
      novel work showed that the 16/6 Id antibody impaired visual memory and spatial
      memory by causing hippocampal injury in mice. Given differences in the cross
      reactivity of each autoantibody with the nervous system, the clinical features
      might be different and diverse in NPLE. Identification of autoantibody targets
      could lead to the development of novel therapies. Investigators and clinicians
      should consider not only the inhibition of autoantibody synthesis but also the
      protection of neuronal cells in the treatment strategy for NPLE.See related
      Research article: http://www.biomedcentral.com/1741-7015/11/90.

PMID- 23556482
TI  - Inflammation in background cirrhosis evokes malignant progression in HCC
      development from HCV-associated liver cirrhosis.
AB  - OBJECTIVE: It is accepted that inflammation promotes malignant progression in the
      development of cancers. Whether, this is true for hepatocellular carcinoma (HCC)
      remains as an open question. We examined the relationship between the
      inflammatory histology activity index (HAI) in the background liver cirrhosis
      (LC) and the histological grading of the HCC in the hepatectomized HCC patients
      with HCV-associated LC. MATERIAL AND METHODS: Out of 264 HCC patients who
      underwent curative hepatic resection, 197 had HCV-associated LC. Among them, 52
      patients with a small solitary HCC nodule (< 5 cm in diameter) were studied.
      Inflammation in the background LC was evaluated by modified Knodell's HAI. To
      evaluate the inflammation, piece meal necrosis, intra lobular cellular
      degeneration and focal necrosis, portal cellular inflammation (0-4, each) were
      estimated. The average HAI was calculated. The grade of malignancy of HCC was
      determined by WHO classification. RESULTS: The average HAI in the 15 patients
      with moderately differentiated HCC (4.3 +/- 0.8, mean +/- SD) was significantly
      larger than that in 11 patients with well differentiated HCC (3.5 +/- 0.6, p =
      0.036). The HAI in the 24 patients whose HCC nodules contained poorly
      differentiated HCC (5.2 +/- 1.1) was significantly larger than that in patients
      with moderately differentiated HCC (p = 0.025). Thus, the HAI order was well
      differentiated group < moderately differentiated group < poorly differentiated
      group. CONCLUSIONS: Inflammation in the background non-cancerous cirrhotic
      portion would evoke malignant progression in HCC development from HCV-associated
      LC.

PMID- 23556483
TI  - Ridicule and being laughed at in the family: gelotophobia, gelotophilia, and
      katagelasticism in young children and their parents.
AB  - The fear of being laughed at (gelotophobia), the joy of being laughed at
      (gelotophilia), and the joy of laughing at others (katagelasticism) were tested
      in a sample of 189 7- and 8-year-olds and their parents (185 mothers, 160
      fathers). The dispositions were widely unrelated in the full sample. There was a
      positive relation between girls' and mothers' katagelasticism as well as between
      the 7-year-old boys' katagelasticism and their parents' gelotophilia.
      Furthermore, the 8-year-old boys' fear of being laughed at correlated robustly
      positively with their parents' gelotophobia and their gelotophilia with their
      parents' katagelasticism. Similarities/dissimilarities in the parental expression
      in the dispositions had no impact on the scores in the children. The findings are
      different from relations reported for parents and their adult children. The study
      provides ground for further studies on how families deal with ridicule and being
      laughed at. 

PMID- 23556485
TI  - Late secondary syphilis with nodular lesions mimicking Kaposi sarcoma in a
      patient with human immunodeficiency virus.

PMID- 23556484
TI  - Skewed X-chromosome inactivation in patients with esophageal carcinoma.
AB  - Skewed X-chromosome inactivation (SXCI) was found in some apparently healthy
      females mainly from Western countries. It has been linked to development of
      ovarian, breast and pulmonary carcinomas. The present study aimed to observe the
      SXCI frequencies in apparently healthy Chinese females and patients with
      esophageal carcinoma. DNA was extracted from the peripheral blood cells from 401
      Chinese females without a detectable tumor and 143 female patients with
      esophageal carcinoma. Exon 1 of androgen receptor (AR) gene was amplified, and
      the products of different CAG alleles were resolved on denaturing polyacrylamide
      gels and visualized after silver staining. The corrected ratios (CR) of the
      products before and after HpaII digestion were calculated. As to the healthy
      females, when CR >= 3 was used as a criterion, SXCI was found in two (4.3%) of
      the 46 neonates, 13 (7.8%) of the 166 younger adults (16-50 years) and 37 (25.7%)
      of the 144 elderly females (51-96 years), with the frequency higher in the
      elderly subjects than in the two former groups (P < 0.05). When a more stringent
      criterion (CR >= 10) was used, SXCI was found in one (2.2%), two (1.2%) and 16
      (11.1%) of the subjects in the three age groups, respectively, itsfrequency being
      higher in the elderly than in the younger age groups (P < 0.05). Occurrence of
      SXCI was detected in both the patients and controls at similar frequencies.
      However, the phenomenon, as defined as CR >= 3, was more frequent in the patients
      aging <40 years (35.7%) compared to the corresponding reference group (7.6%, P =
      0.006). When CR >= 10 was adopted, the frequencies were 7.1% and 1.2%,
      respectively. Their difference did not attain statistical significance (P = 0.
      217). SXCI also occurs in apparently healthy Chinese females, and is associated
      with age. It may be considered as a predisposing factor for the early development
      of esophageal carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here http://www.diagnosticpathology.diagnomx.eu/vs/1542364337927656.

PMID- 23556486
TI  - Assessment of intraoperative microaspiration: does a modified cuff shape improve
      sealing?
AB  - BACKGROUND: Intra-operative aspiration of oropharyngeal secretions is associated
      with post-operative pneumonia. The use of endotracheal tubes (ETTs) with a
      modified cuff shape could be one preventive action. In this clinical,
      prospective, randomised controlled trial, we hypothesised that altering the cuff
      shape to a tapered shape could reduce the aspiration incidence. The primary
      outcome was aspiration of dye solution into the trachea. METHODS: Patients
      scheduled for lumbar surgery were intubated with either an ETT with a barrel
      shaped polyvinylchloride cuff (control group, n = 30) or tapered-shaped
      polyvinylchloride cuff (intervention group, n = 30). Subsequently, instillation
      with methylthioninium chloride was performed. At 10, 30, 60, 90, and 120 min
      after intubation, bronchoscopy was performed assessing the degree of dye descent
      along the cuff and digitally stored. Single blind review of the videoclips
      provided data on incidence of dye aspiration and depth of penetration along the
      cuff. RESULTS: The traditional cuff showed descent of dye into the trachea in 20%
      of the patients. Although a tapered-shaped polyvinylchloride cuff leaked up to
      the second third of the cuff, no dye leakage into the trachea was observed. The
      use of a tapered-shaped cuff had a protective role against aspiration (T30: OR
      3.0, CI 1.57-5.75; P = 0.001). CONCLUSIONS: Short-term use of tapered-shaped
      polyvinylchloride cuffs in surgical patients results in more effective sealing of
      the tracheal lumen in comparison with a traditional barrel-shaped
      polyvinylchloride cuffs. Further evaluation is needed to determine whether a
      reduction in post-operative pneumonia can be demonstrated when these cuffs are
      used.

PMID- 23556487
TI  - The role of magnetic resonance imaging in prostate cancer.

PMID- 23556488
TI  - How others see us.

PMID- 23556489
TI  - Potential preventive measures against quad bike injuries.

PMID- 23556491
TI  - Subcutaneous emphysema of the neck following radical prostatectomy.

PMID- 23556492
TI  - Lung carcinoid with pulmonary vein and left atrial neoplastic thrombus.

PMID- 23556493
TI  - Glomus tumour of the fingertip.

PMID- 23556494
TI  - Practical aspects of clinical photography: Part 2 - Data management, ethics and
      quality control.

PMID- 23556495
TI  - Bugosa hernia: a hernia of the conjoint tendon.

PMID- 23556496
TI  - Response from Dr Thomson et al. to Mortality rates after surgery in New South
      Wales.

PMID- 23556497
TI  - Response from Dr McCulloch to Mortality rates after surgery in New South Wales.

PMID- 23556498
TI  - Re: Response from Dr Thomson et al. to Mortality rates after surgery in New South
      Wales.

PMID- 23556499
TI  - Re: Response from Dr McCulloch to Mortality rates after surgery in New South
      Wales.

PMID- 23556500
TI  - Heterotopic ossification in the reaming tract of a percutaneous antegrade femoral
      nail: a case report.
AB  - INTRODUCTION: Heterotopic ossification is a rare complication of musculoskeletal
      injuries, characterized by bone growth in soft tissues. Percutaneous antegrade
      intramedullary nailing represents the 'gold standard' for the treatment of femur
      shaft fractures. Minor bone growth is frequently seen around the proximal end of
      reamed femoral nails (so-called 'callus caps'), which are asymptomatic and lack a
      therapeutic implication. The occurrence of excessive, symptomatic heterotopic
      ossification around the entry site of an antegrade femoral nail is rarely
      described in the literature. CASE PRESENTATION: We present the case of a 28-year
      old Caucasian woman who developed extensive heterotopic ossification around the
      reaming seeds of a reamed femoral nail. She developed severe pain and
      significantly impaired range of motion of the hip joint, requiring revision
      surgery for heterotopic ossification resection and adjunctive local irradiation.
      She recovered full function of the hip and remained asymptomatic at her two-year
      follow-up appointment. CONCLUSIONS: Severe heterotopic ossification represents a
      rare but potentially detrimental complication after percutaneous femoral nailing
      of femur shaft fractures. Diligent care during the reaming procedure, including
      placement of a trocar to protect from osteogenic seeding of the soft tissues, may
      help decrease the risk of developing heterotopic ossification after reamed
      antegrade femoral nailing.

PMID- 23556501
TI  - Identification and antifungal susceptibility of fungi isolated from
      dermatomycoses.
AB  - BACKGROUND: Dermatomycoses are superficial fungal infections of the skin, hair
      and nails that affect more than 20-25% of the people worldwide. These infections
      can be caused by yeasts, dermatophytes and non-dermatophyte filamentous fungi
      (NDFF) and are considered a public health problem. Despite this, few studies have
      investigated the prevalence and antifungal susceptibility of causative agents of
      dermatomycoses in the developing world. OBJECTIVES: The aims of this study were
      to identify and determine the antifungal susceptibility profile of yeast and
      filamentous fungi isolated from dermatomycoses in Uberaba, Minas Gerais, Brazil.
      METHODS: Specimens were obtained from patients with clinically diagnosed and
      laboratory confirmed dermatomycosis between July 2009 and July 2011. Fungal
      identification was based on classical methods and antifungal susceptibility
      testing was performed by broth microdilution method. RESULTS: Of the 216 fungal
      isolates, 116 (53.8%) were yeasts, 70 (32.4%) dermatophytes and 30 (13.8%) NDFF.
      Onychomycosis was the most common clinical condition. Candida parapsilosis
      (24.1%) and Trichophyton rubrum (17.1%) were the fungi most frequently isolated.
      Voriconazole, ketoconazole and itraconazole were the most potent antifungal
      agents against yeast, whereas terbinafine, voriconazole and itraconazole had a
      high in vitro activity against dermatophytes. Overall, the antifungal agents had
      little or no activity against NDFF and the highest minimum inhibitory
      concentrations were those against Fusarium spp. CONCLUSION: Yeasts, particularly
      C. parapsilosis, play an important role as causative agents of dermatomycosis in
      our region. Our results suggest that the antifungal susceptibility testing
      coupled with proper identification of the fungi may be useful to assist
      clinicians in determining the appropriate therapy for dermatomycoses.

PMID- 23556503
TI  - Origin of hydrophobicity in FIB-nanostructured Si surfaces.
AB  - Surface morphology has been demonstrated to influence the tribological properties
      at different scales, but the phenomena which occur at the nanoscale have not been
      completely understood. The present study reports on the effect of focused ion
      beam nanopatterning on coefficient of friction (CoF) and adhesion of Si(001)
      surface covered by native oxide. Regular arrays of nanogrooves reduce both CoF
      and adhesion, related to a hydrophobic character of the patterned surface, but
      this effect disappears as soon as the separation among the nanostructures
      approaches the microscopic scale. The dependence of this hydrophobic effect on
      the pitch is not linked to the corresponding contact area. It has been found that
      each nanostructure is surrounded by a low-friction region which extends some
      hundreds of nanometers from it. For pitches of 125 and 250 nm these low-friction
      regions completely overlap, generating a consistent decrease in CoF and adhesion,
      while for pitches of 500 and 1000 nm their effect is negligible. The low-friction
      regions were not observed in humidity-free ambient, indicating that they are the
      origin of patterns of hydrophobicity.

PMID- 23556502
TI  - Repair of postpneumonectomy bronchopleural fistula using pedicled pericardial
      flap supported by fibrin glue.
AB  - Effective closure of the postpneumonectomy bronchopleural fistula (PBF) with the
      use of different techniques still remains a challenge for thoracic surgeons. The
      aim of this study was to evaluate the efficacy of modified method of PBF closure
      using pedicled pericardial flap (PPF) supported by fibrin glue (FG). The efficacy
      of the late PBF closure with the use of two surgical methods was compared. In 10
      patients, the edges of the PBF were covered with FG and PPF. In the second group
      of nine patients, myoplasty was used to close the bronchial fistula. Postsurgical
      follow-up was for 1 year. In the first group, the healing of the fistula was
      achieved in 100% of the cases, whereas in the second, myoplasty group, healing
      was achieved in only 66.67% of the cases. The number of complications was similar
      in both groups. Pericardial flap supported by fibrin glue can be an effective
      method adjunctive to the treatment of PBF in selected patients.

PMID- 23556504
TI  - Correlates of suicide stigma and suicide literacy in the community.
AB  - Public knowledge and attitudes toward suicide may influence help-seeking for
      suicidality. This study aimed to identify correlates of suicide attitudes and
      knowledge. Australian adults were invited to complete an online survey, with
      1,286 responders. Less exposure to suicide, older age, male gender, less
      education, and culturally diverse backgrounds were associated with poorer
      knowledge; while younger age, male gender, and culturally diverse backgrounds
      were associated with more stigmatizing attitudes toward people who die by
      suicide. The results suggest suicide literacy and stigma reduction programs would
      benefit community members, particularly males and individuals from culturally
      diverse backgrounds. 

PMID- 23556506
TI  - Potential pathogenetic role of Th17, Th0, and Th2 cells in erosive and reticular
      oral lichen planus.
AB  - OBJECTIVES: The role of Th17 cells and associated cytokines was investigated in
      oral lichen planus. MATERIAL AND METHODS: 14 consecutive patients with oral
      lichen planus were investigated. For biological studies, tissues were taken from
      reticular or erosive lesions and from normal oral mucosa (controls) of the same
      patient. mRNA expression for IL-17F, IL-17A, MCP-1, IL-13, IL-2, IL-10, IL-1beta,
      RANTES, IL-4, IL-12B, IL-8, IFN-gamma, TNF-alpha, IL-1alpha, IL-18, TGF-beta1, IL
      23R, IL-7, IL-15, IL-6, MIG, IP-10, LTB, VEGF, IL-5, IL-27, IL-23A, GAPDH, PPIB,
      Foxp3, GATA3, and RORC was measured using the QuantiGene 2.0. RESULTS: Results
      showed that Th17-type and Th0-type molecules' mRNAs, when compared with results
      obtained from tissue controls, were increased in biopsies of erosive lesions,
      whereas Th2-type molecules' mRNAs were increased in reticular lesions. When the
      CD4+ T-cell clones, derived from oral lichen planus tissues and tissue controls,
      were analyzed, a higher prevalence of Th17 (confirmed by an increased CD161
      expression) and Th0 CD4+ T clones was found in erosive lesions, whereas a
      prevalence of Th2 clones was observed in reticular lesions. CONCLUSIONS: Our data
      suggest that Th17, Th0, and Th2 cells, respectively, may have a role in the
      pathogenesis of erosive and reticular oral lichen planus.

PMID- 23556505
TI  - Weight gain prevention in young adults: design of the study of novel approaches
      to weight gain prevention (SNAP) randomized controlled trial.
AB  - BACKGROUND: Weight gain during young adulthood is common and is associated with
      increased cardiovascular risk. Preventing this weight gain from occurring may be
      critical to improving long-term health. Few studies have focused on weight gain
      prevention, and these studies have had limited success. SNAP (Study of Novel
      Approaches to Weight Gain Prevention) is an NIH-funded randomized clinical trial
      examining the efficacy of two novel self-regulation approaches to weight gain
      prevention in young adults compared to a minimal treatment control. The
      interventions focus on either small, consistent changes in eating and exercise
      behaviors, or larger, periodic changes to buffer against expected weight gains.
      METHODS/DESIGN: SNAP targets recruitment of six hundred young adults (18-35
      years) with a body mass index between 21.0-30.0 kg/m2, who will be randomly
      assigned with equal probability to: (1) minimal intervention control; (2) self
      regulation with Small Changes; or (3) self-regulation with Large Changes. Both
      interventions receive 8 weekly face-to-face group sessions, followed by 2 monthly
      sessions, with two 4-week refresher courses in each of subsequent years.
      Participants are instructed to report weight via web at least monthly thereafter,
      and receive monthly email feedback. Participants in Small Changes are taught to
      make small daily changes (~100 calorie changes) in how much or what they eat and
      to accumulate 2000 additional steps per day. Participants in Large Changes are
      taught to create a weight loss buffer of 5-10 pounds once per year to protect
      against anticipated weight gains. Both groups are encouraged to self-weigh daily
      and taught a self-regulation color zone system that specifies action depending on
      weight gain prevention success. Individualized treatment contact is offered to
      participants who report weight gains. Participants are assessed at baseline, 4
      months, and then annually. The primary outcome is weight gain over an average of
      3 years of follow-up; secondary outcomes include diet and physical activity
      behaviors, psychosocial measures, and cardiovascular disease risk factors.
      DISCUSSION: SNAP is unique in its focus on weight gain prevention in young
      adulthood. The trial will provide important information about whether either or
      both of these novel interventions are effective in preventing weight gain. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT01183689.

PMID- 23556507
TI  - Impact of an educational program on the use of standardized nursing languages for
      nursing documentation among public health nurses in Nigeria.
AB  - PURPOSE: To measure the effect of an educational package on documentation of care
      among public health nurses (PHNs). METHOD: A quasi-experimental design was
      adopted. Forty PHNs working in primary healthcare settings were selected.
      Education was given through a 5-day workshop. Documentation of care was assessed
      using a modified "Muller-Staub Q-DIO instrument." Data were analyzed using t test
      third and twelfth months postintervention. FINDINGS: There was a significant
      improvement on documentation of care at p = .0001. CONCLUSION: Educating PHNs and
      providing them with standardized nursing care plans enhance documentation of
      care. IMPLICATION TO PRACTICE: A combination of education on the use of
      standardized nursing languages and standardized nursing care plans can enhance
      documentation of care. There is a need for more research on the use of
      standardized nursing languages in developing nations.

PMID- 23556508
TI  - Pilar cysts and smoking.

PMID- 23556509
TI  - Kinetically controlling phase transformations of crystalline mercury
      selenidostannates through surfactant media.
AB  - Herein we report the surfactant-thermal method to prepare two novel one
      dimensional mercury selenidostannates, [DBUH]2[Hg2Sn2Se6(Se2)] (1) and
      [DBUH]2[Hg2Sn2Se7] (2), where DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, by
      applying PEG-400 as the reaction medium. It is worth noting that 1 is kinetically
      stable and can be transformed into thermodynamically stable phase 2 under a
      longer reaction time. Our strategy "growing crystalline materials in surfactants"
      could open a new door to preparing novel crystals with diverse structures and
      interesting properties.

PMID- 23556510
TI  - Rubella seroprevalence among pregnant women in Burkina Faso.
AB  - BACKGROUND: Despite the serious consequences of rubella infection during early
      pregnancy, very little is known about the rubella seroprevalence in a number of
      African countries including Burkina Faso. METHODS: Between December 2007 and
      March 2008 serum samples were collected from 341 pregnant women in Bobo (n = 132,
      urban area) and Hounde (n = 209, rural area) and were tested for rubella-specific
      IgG antibodies with a commercial ELISA kit. RESULTS: An overall seropositivity
      rate of 95.0% (324/341) was found, with a higher percentage in the urban
      population and in the oldest age group. Considering an antibody titer of at least
      10 International Units per ml as protective, the overall immunity rate in the
      cohort of pregnant women was 93.3% (318/341). CONCLUSIONS: The high overall
      seropositivity rate in the absence of routine immunization suggests a continuous
      transmission of endemic rubella virus in Burkina Faso, posing a threat to non
      immune pregnant women.

PMID- 23556512
TI  - Pulmonary manifestations in Behcet disease: impaired natural killer cells
      activity.
AB  - BACKGROUND: Behcet's disease (BD) is a systemic vasculitis with unknown
      aetiology, where, besides genetic predisposition, an immune dysregulation
      involving T and B lymphocytes and hyperactive neutrophils contribute to disease
      pathogenesis. The aim of this study was to determine the cytotoxicity of natural
      killer (NK) cells in bronchoalveolar lavage (BAL) from BD patients with pulmonary
      manifestations. METHODS: BAL was performed in 27 patients with BD and pulmonary
      manifestations, 14 patients with Rheumatoid Arthritis (RA) and 23 healthy
      controls (HC). Related orphan receptor C (RORC) and forkheadbox P3 (FOXP3) mRNA
      transcript were determined in BAL by reverse transcription-polymerase chain
      reaction (RT-PCR). NK cells, NK cell cytotoxicity, and lymphokine-activated
      killer (LAK) activity against K562 cells were measured by flow cytometry.
      Proportions of NK precursors and expression of genes for IL-2 receptor beta (IL
      2Rbeta; CD122), perforin, and granzyme in NK cells were measured by flow
      cytometry or RT-PCR. RESULTS: The analysis of transcription factors revealed an
      increase in the RORC/FOXP3 ratio (Th17/Treg cells) in BAL from BD patients.
      Percentages of NK were significantly lower in BD than in RA patients and healthy
      controls. Purified NK cells derived from BD patients were found to have lower
      cytotoxicity and LAK activity than those from controls. This defect of NK cells
      in BD patients was related to down-regulation of perforin and granzyme expression
      in NK cells. CONCLUSION: In BD patients, the increased RORC/FOXP3 ratio indicated
      an inflammatory state of the lung. NK cells were decreased together with an
      impairment of their activity due to a defective expression of granzyme and
      perforin. These abnormalities possibly contribute to immune system dysregulation
      found in BAL of BD patients with pulmonary manifestations.

PMID- 23556511
TI  - Engineering of papaya mosaic virus (PapMV) nanoparticles with a CTL epitope
      derived from influenza NP.
AB  - BACKGROUND: The ever-present threat of infectious disease, e.g. influenza
      pandemics, and the increasing need for new and effective treatments in
      immunotherapy are the driving forces that motivate research into new and
      innovative vaccine platforms. Ideally, such platforms should trigger an efficient
      CTL response, be safe, and easy to manufacture. We recently developed a novel
      nanoparticle adjuvant comprised of papaya mosaic virus (PapMV) coat protein (CP)
      assembled around an RNA. The PapMV nanoparticle is an efficient vaccine platform
      in which the peptide antigen is fused to the C-terminus of the PapMV CP, leading
      to nanoparticles presenting surface-exposed epitope. The fusion stabilizes the
      epitope and improves its immunogenicity. We found recently that C-terminal
      fusions are not always efficient, depending on the nature of the peptide fused to
      the platform. RESULTS: We chose a CTL epitope derived from the nucleocapsid (NP)
      of influenza virus (NP147-155) for this proof-of-concept demonstration.
      Recombinant nanoparticles harbouring a fusion at the N-terminus were more
      efficient in triggering a CTL response. Efficacy appeared to be linked to the
      stability of the nanoparticles at 37 degrees C. We also showed that discs-
      smaller than nanoparticles--made of 20 subunits of PapMV CP are less efficient
      for induction of a CTL response in mice, revealing that assembly of the
      recombinant PapMV CP into nanoparticles is crucial to triggering an efficient CTL
      response. CONCLUSION: The point of fusion on the PapMV vaccine platform is
      critical to triggering an efficient CTL response. Efficacy is linked to
      nanoparticle stability; nanoparticles must be stable at 37 degrees C but remain
      susceptible to cellular proteases to ensure efficient processing of the CTL
      epitope by cells of the immune system. The results of this study improve our
      understanding of the PapMV vaccine platform, which will facilitate the design of
      efficient vaccines to various infectious threats.

PMID- 23556513
TI  - Decoherence cross-section in NO + Ar collisions: experimental results and a
      simple model.
AB  - Quantum decoherence can be viewed as the mechanism responsible for the quantum-to
      classical transition as the initially prepared quantum state interacts with its
      environment in an irreversible manner. One of the most common mechanisms
      responsible for the macroscopically observed decoherence involves collisions of
      an atom or molecule, initially prepared in a coherent superposition of states,
      with gas particles. In this work, a coherent superposition of quantum internal
      states of NO molecules is prepared by the interaction between the molecule with
      both a static and a radiofrequency electric field. Subsequently, NO + Ar
      collision decoherence experiments are investigated by measuring the loss of
      coherence as a function of the number of collisions. Data analysis using a model
      based on the interaction potential of the collisional partners allowed to unravel
      the molecular mechanism responsible for the loss of coherence in the prepared NO
      quantum superposition of internal states. The relevance of the present work
      relies on several aspects. On the one hand, the use of radio-waves introduces a
      new way for the production of coherent beams. On the other hand, the employed
      methodology could be useful in investigating the Stereodynamics of chemical
      reactions with coherent reagents. 

PMID- 23556514
TI  - Rapid anti-transglutaminase assay and patient interview for monitoring dietary
      compliance in celiac disease.
AB  - OBJECTIVE: The anti-transglutaminase antibodies (anti-tTG) play an important role
      in monitoring the celiacs' gluten-free diet (GFD). MATERIAL AND METHODS: The
      authors propose to use the rapid IgA anti-tTG assay based on a whole blood drop
      to evaluate the compliance to GFD at the clinical ambulatory setting. The rapid
      test results were compared with those of the conventional ELISA assay and with
      dietary compliance reported by patients' interview. CONCLUSIONS: The authors
      showed that anti-tTG rapid test is reliable and easy to perform in the ambulatory
      setting to evaluate dietary compliance. Moreover, they proved that celiacs'
      interview is more sensitive than serology in identifying patients who transgress.

PMID- 23556515
TI  - Palladium-catalyzed desulfitative cross-coupling reaction of sodium sulfinates
      with benzyl chlorides.
AB  - A palladium-catalyzed approach for the synthesis of diarylmethanes from sodium
      sulfinates and benzyl chlorides is described. Various aromatic sodium sulfinates
      were used as aryl sources via extrusion of SO2 and gave the diarylmethanes in
      moderate to good yields.

PMID- 23556516
TI  - Impaired outcome of controlled ovarian hyperstimulation in women with thyroid
      autoimmune disease.
AB  - BACKGROUND: Controlled ovarian hyperstimulation (COH) is a crucial step of
      assisted reproductive technology (ART). Thyroid dysfunction and autoimmune
      thyroid disease (ATD) may negatively affect the outcome of ART, but the
      underlying mechanisms are still poorly understood. Our aim was to evaluate the
      respective role of ATD and thyroid function, as assessed by serum thyrotropin
      (TSH), on the early outcome of COH. METHODS: In total, 262 (202 ATD-negative and
      60 ATD-positive) euthyroid subfertile women underwent ART. Before COH, serum
      follicle-stimulating hormone (FSH), luteinizing hormone, and estradiol (E2) were
      measured at cycle day 3, and progesterone at cycle day 21. At oocyte pickup and
      at embryo transfer, we evaluated the performance of recombinant FSH (r-FSH), as
      assessed by serum E2 concentration/total administered r-FSH units (E2/r-FSH)
      ratio and by oocyte quality. RESULTS: At both oocyte pickup and embryo transfer,
      the performance of r-FSH was significantly poorer in ATD-positive than in ATD
      negative women. In the ATD-positive group, women with a TSH <2.5 mIU/L displayed
      a higher serum E2 concentration at oocyte pickup, a higher E2/r-FSH ratio, and a
      greater number of mature metaphase II oocytes than women with a TSH >2.5 mIU/L.
      When ATD-positive women were divided into quartiles according to their serum TSH
      level, both the ovarian response to r-FSH and the number of mature metaphase II
      oocytes significantly increased from the lowest to the highest quartiles of serum
      TSH concentration. CONCLUSIONS: ATD has a negative effect on the early outcome of
      COH, but this negative influence may be avoided with adequate levothyroxine
      therapy aimed at keeping TSH <2.5 mU/L. Thyroid antibodies and serum TSH should
      be checked in any woman undergoing ART.

PMID- 23556517
TI  - Current state of orthodontic patients under bisphosphonate therapy.
AB  - BACKGROUND: Bisphosphonates are a common medication for the prevention and
      therapy of osteoporosis, but are also applied for tumor diseases. They affect
      bone metabolism, and therefore also orthodontic treatments, but how it does has
      yet not been definitively clarified. Therefore, the aim of this research was to
      evaluate and demonstrate the reported effects and the current state of scientific
      research regarding orthodontic treatment and bisphosphonate medication
      exclusively in humans. MATERIAL AND METHODS: A systematic research of the
      literature for selected keywords in the Medline database (Pubmed) as well as a
      manual search was conducted. The following search terms were used:
      'Bisphosphonate' in combination with: orthodontic, orthodontic treatment, tooth
      movement. FINDINGS: To date, only nine reported patients (case reports/series)
      and one original article (retrospective cohort study) regarding orthodontic
      treatment under bisphosphonate medication in humans have been published.
      Decelerated tooth movement with increased side effects (especially in high-risk
      patients) and longer treatment duration was reported in some articles. Patients
      with initial spacing or extraction cases had a higher risk of incomplete space
      closure and poor root parallelism. CONCLUSIONS: Orthodontic tooth movement under
      bisphosphonate medication is possible, especially in low-risk patients (low dose
      and short period of intake). But the treatment is still not predictable,
      especially in high-risk patients. Therefore, the altered bone metabolism and
      higher extent of side effects should be considered in treatment planning,
      especially in extraction cases or high-risk patients. Regardless, longer
      treatment duration, decelerated tooth movement, and more side effects, e.g.,
      incomplete space closure and poor root parallelism, should be expected,
      especially in extraction cases or space closure.

PMID- 23556519
TI  - Coping strategies for child bully-victims.

PMID- 23556518
TI  - N-linked glycosylation is required for transferrin-induced stabilization of
      transferrin receptor 2, but not for transferrin binding or trafficking to the
      cell surface.
AB  - Transferrin receptor 2 (TfR2) is a member of the transferrin receptor-like family
      of proteins. Mutations in TfR2 can lead to a rare form of the iron overload
      disease, hereditary hemochromatosis. TfR2 is proposed to sense body iron levels
      and increase the level of expression of the iron regulatory hormone, hepcidin.
      Human TfR2 (hTfR2) contains four potential Asn-linked (N-linked) glycosylation
      sites on its ectodomain. The importance of glycosylation in TfR2 function has not
      been elucidated. In this study, by employing site-directed mutagenesis to remove
      glycosylation sites of hTfR2 individually or in combination, we found that hTfR2
      was glycosylated at Asn 240, 339, and 754, while the consensus sequence for N
      linked glycosylation at Asn 540 was not utilized. Cell surface protein
      biotinylation and biotin-labeled Tf indicated that in the absence of N-linked
      oligosaccharides, hTfR2 still moved to the plasma membrane and bound its ligand,
      holo-Tf. However, without N-linked glycosylation, hTfR2 did not form the
      intersubunit disulfide bonds as efficiently as the wild type (WT). Moreover, the
      unglycosylated form of hTfR2 could not be stabilized by holo-Tf. We further
      provide evidence that the unglycosylated hTfR2 behaved in manner different from
      that of the WT in response to holo-Tf treatment. Thus, the putative iron-sensing
      function of TfR2 could not be achieved in the absence of N-linked
      oligosaccharides. On the basis of our analyses, we conclude that unlike TfR1, N
      linked glycosylation is dispensable for the cell surface expression and holo-Tf
      binding, but it is required for efficient intersubunit disulfide bond formation
      and holo-Tf-induced stabilization of TfR2. 

PMID- 23556520
TI  - A review of Munchausen syndrome by proxy.

PMID- 23556521
TI  - Neglect in children.

PMID- 23556522
TI  - Dramatic data about smoking and life expectancy.

PMID- 23556524
TI  - Impact on pediatrics of proposed DSM-5 changes to mental disorder diagnostic
      criteria.

PMID- 23556525
TI  - A 13-year-old girl with pancytopenia. Catastrophic antiphospholipid syndrome.

PMID- 23556526
TI  - Delayed introduction of solid foods to infants: not so fast!

PMID- 23556528
TI  - Child and adolescent mental health.

PMID- 23556527
TI  - A 13-year-old boy with pharyngitis, oral ulcers, and dehydration. Mycoplasma
      pneumoniae-associated mucositis.

PMID- 23556529
TI  - DSM-5 and proposed changes to the diagnosis of autism.

PMID- 23556530
TI  - Working with families perceived as difficult.

PMID- 23556531
TI  - A conversation with David W. Kimberlin, MD, FAAP.

PMID- 23556532
TI  - Dermatologist and gastroenterologist awareness of the potential of
      immunosuppressants used to treat inflammatory bowel disease to cause non-melanoma
      skin cancer.
AB  - BACKGROUND:   Immunosuppressants used to treat inflammatory bowel disease (IBD)
      may contribute towards the development of non-melanoma skin cancer (NMSC). Few
      studies have documented this increase in risk. METHODS:   A mail-in survey was
      sent to practicing dermatologists and gastroenterologists in the state of Hawaii,
      USA. These physicians were asked if they had patients with IBD on
      immunosuppressants with NMSC and if they were aware of an association between
      immunosuppressants used in IBD and the occurrence of NMSC. Physicians were
      located via the Yellow Pages telephone directory and the websites
      http://www.healthgrades.com and http://www.ucomparehealthcare.com. RESULTS:   Of
      the 96 surveys delivered, 45 were returned for analysis. Overall, 73.3% of
      responding physicians knew about an association between NMSC and
      immunosuppressants for IBD, but 26.7% had no knowledge of this association. When
      respondents were categorized according to specialty, 90.9% of dermatologists
      reported knowing about this association, but only 46.2% of responding
      gastroenterologists reported this awareness (P = 0.0034). Of the respondents who
      did not provide details of their specialty, 70.0% reported knowledge of the
      association. CONCLUSIONS:   Immunosuppressants are helpful in controlling IBD
      symptoms and progression but should only be used after a thorough assessment of
      their risks and benefits in each patient. After the initiation of
      immunosuppressants, patients should have access to appropriate preventative and
      treatment modalities for NMSC.

PMID- 23556534
TI  - Evaluation of vitreous clearance and potential retinal toxicity of intravitreal
      lornoxicam (xefo).
AB  - PURPOSE: To evaluate the vitreous clearance and toxicological profile of
      commercially available lornoxicam (Xefo), after a single intravitreal injection
      in rabbits. METHODS: Twenty-five male albino rabbits (10 rabbits were used for
      retinal toxicity evaluation, while 15 rabbits were used to evaluate vitreous
      clearance) were used in this study. Two concentrations of lornoxicam were tested
      for retinal toxicity: 250 MUg/0.1 mL and 1,500 MUg/0.1 mL. Each concentration was
      intravitreally injected randomly in 1 eye of each rabbit (group I received 250
      MUg/0.1 mL, n=5 and group II received 1,500 MUg/0.1 mL, n=5), while in the other
      eye 0.1 mL of sterile balanced saline solution was injected. Slit-lamp and
      funduscopic examinations along with intraocular pressure measurements (IOP) were
      performed prior to injection and at days 1, 15, and 30 after the injection for
      signs of infection, inflammation, toxicity, and IOP changes. A baseline
      electroretinogram (ERG) was performed before the experiment and at days 1, 15,
      and 30 after the intravitreal injection. At the last follow-up day, the animals
      were sacrificed and the enucleated eyes were prepared for histological evaluation
      of the retina. Lornoxicam (concentration of intravitreal injection: 250 MUg/0.1
      mL) clearance from the vitreous was estimated using high-performance liquid
      chromatography in 30 rabbit eyes. RESULTS: There were no statistical differences
      between the control and experimental eyes, concerning ERG amplitudes and IOP
      measurements for both groups (I and II), at all examinations. On the contrary,
      histological examination of the samples revealed extended retinal damage of group
      II experimental eyes (morphological alterations at the level of the inner nuclear
      and outer plexiform layers was evident along with disappearance of normal
      stratification of outer retina with vacuolization and thinning), whereas the
      morphology of group I experimental eyes did not differ from that of the control
      eyes. Lornoxicam is eliminated from the vitreous by a first-order kinetic process
      with a half-life of 1.7 h. CONCLUSIONS: Intravitreal lornoxicam causes dose
      related toxic effect to the retina at a concentration of 1,500 MUg. A dose of 250
      MUg does not seem to cause histological toxic effects at the level of the retina.
      Lornoxicam could be considered with interest for further research for the
      development of alternative treatments for ocular inflammatory conditions.

PMID- 23556535
TI  - Regularization in finite mixture of regression models with diverging number of
      parameters.
AB  - Feature (variable) selection has become a fundamentally important problem in
      recent statistical literature. Sometimes, in applications, many variables are
      introduced to reduce possible modeling biases, but the number of variables a
      model can accommodate is often limited by the amount of data available. In other
      words, the number of variables considered depends on the sample size, which
      reflects the estimability of the parametric model. In this article, we consider
      the problem of feature selection in finite mixture of regression models when the
      number of parameters in the model can increase with the sample size. We propose a
      penalized likelihood approach for feature selection in these models. Under
      certain regularity conditions, our approach leads to consistent variable
      selection. We carry out extensive simulation studies to evaluate the performance
      of the proposed approach under controlled settings. We also applied the proposed
      method to two real data. The first is on telemonitoring of Parkinson's disease
      (PD), where the problem concerns whether dysphonic features extracted from the
      patients' speech signals recorded at home can be used as surrogates to study PD
      severity and progression. The second is on breast cancer prognosis, in which one
      is interested in assessing whether cell nuclear features may offer prognostic
      values on long-term survival of breast cancer patients. Our analysis in each of
      the application revealed a mixture structure in the study population and
      uncovered a unique relationship between the features and the response variable in
      each of the mixture component.

PMID- 23556533
TI  - Novel aspects of Sjogren's syndrome in 2012.
AB  - Sjogren's syndrome (SS) is a systemic progressive autoimmune disease
      characterized by a complex pathogenesis requiring a predisposing genetic
      background and involving immune cell activation and autoantibody production. The
      immune response is directed to the exocrine glands, causing the typical 'sicca
      syndrome', but major organ involvement is also often seen. The etiology of the
      disease is unknown. Infections could play a pivotal role: compared to normal
      subjects, patients with SS displayed higher titers of anti-Epstein-Barr virus
      (EBV) early antigens, but lower titers of other infectious agent antibodies such
      as rubella and cytomegalovirus (CMV) suggest that some infections may have a
      protective role against the development of autoimmune disease. Recent findings
      seem to show that low vitamin D levels in patients with SS could be associated
      with severe complications such as lymphoma and peripheral neuropathy. This could
      open new insights into the disease etiology. The current treatments for SS range
      from symptomatic therapies to systemic immunosuppressive drugs, especially B cell
      targeted drugs in cases of organ involvement. Vitamin D supplementation may be an
      additional tool for optimization of SS treatment.

PMID- 23556537
TI  - Detection of expression of IL-18 and its binding protein in Egyptian pediatric
      immune thrombocytopenic purpura.
AB  - Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, characterized by
      dysfunctional cellular immunity including the presence of activated platelet
      specific autoreactive T cells that recognize and respond to autologous platelet
      antigens. Autoreactive T cells drive the generation of platelet reactive
      autoantibodies by B cells as well as T-cytotoxic cell-mediated lysis of
      platelets. Interleukin-18 (IL-18) is a mediator of T helper type 1 cell responses
      synergistically with IL-12 that initiate and promote host defense and
      inflammation. IL-18 has a specific binding protein (IL-18BP) which belongs to the
      immunoglobulin superfamily. In the present study, serum level and messenger RNA(
      mRNA) expression of IL-18 as well as IL-18BP mRNA expression were measured in
      peripheral blood mononuclear cells (PBMNCs) of 100 Egyptian pediatric patients
      with ITP (70 acute and 30 chronic). In addition to this, we recruited 80 healthy
      volunteers in order to investigate the possible association between the imbalance
      of IL-18 and IL-18 BP expressions and the pathogenesis of ITP. IL-18 serum level
      and mRNA expression were not elevated in cases more than in the control group,
      but IL-18 mRNA was higher in chronic cases when compared to the acute ones
      (p=0.031) and there was a good negative correlation between the platelet count
      and serum IL-18. IL-18 BP m-RNA was slightly elevated in cases more than in the
      control group (95% Confidence interval=1.15-2.01). Our results were not
      supportive for previous findings of elevated IL18/BP mRNA ratio in ITP patients.
      This could be referred to the fact that autoimmune diseases are complex genetic
      disorders, therefore further studies on polymorphisms affecting IL-18 gene
      expression as well as kinetics of IL-18 expression are required to evaluate the
      role of interleukin 18 and its binding protein in the pathogenesis of ITP.

PMID- 23556538
TI  - Influence of oxic/anoxic fluctuations on ammonia oxidizers and nitrification
      potential in a wet tropical soil.
AB  - Ammonia oxidation is a key process in the global nitrogen cycle. However, in
      tropical soils, little is known about ammonia-oxidizing microorganisms and how
      characteristically variable oxygen regimes affect their activity. We investigated
      the influence of brief anaerobic periods on ammonia oxidation along an elevation,
      moisture, and oxygen availability gradient in wet tropical soils. Soils from
      three forest types were incubated for up to 36 weeks in lab microcosms under
      three regimes: (1) static aerobic; (2) static anaerobic; and (3) fluctuating
      (aerobic/anaerobic). Nitrification potential was measured in field-fresh soils
      and incubated soils. The native ammonia-oxidizing community was also
      characterized, based on diversity assessments (clone libraries) and
      quantification of the ammonia monooxygenase alpha-subunit (amoA) gene. These
      relatively low pH soils appear to be dominated by ammonia-oxidizing archaea
      (AOA), and AOA communities in the three soil types differed significantly in
      their ability to oxidize ammonia. Soils from an intermediate elevation, and those
      incubated with fluctuating redox conditions, tended to have the highest
      nitrification potential following an influx of oxygen, although all soils
      retained the capacity to nitrify even after long anoxic periods. Together, these
      results suggest that wet tropical soil AOA are tolerant of extended periods of
      anoxia.

PMID- 23556536
TI  - How many signal peptides are there in bacteria?
AB  - Over the last 5 years proteogenomics (using mass spectroscopy to identify
      proteins predicted from genomic sequences) has emerged as a promising approach to
      the high-throughput identification of protein N-termini, which remains a problem
      in genome annotation. Comparison of the experimentally determined N-termini with
      those predicted by sequence analysis tools allows identification of the signal
      peptides and therefore conclusions on the cytoplasmic or extracytoplasmic
      (periplasmic or extracellular) localization of the respective proteins. We
      present here the results of a proteogenomic study of the signal peptides in
      Escherichia coli K-12 and compare its results with the available experimental
      data and predictions by such software tools as SignalP and Phobius. A single
      proteogenomics experiment recovered more than a third of all signal peptides that
      had been experimentally determined during the past three decades and confirmed at
      least 31 additional signal peptides, mostly in the known exported proteins, which
      had been previously predicted but not validated. The filtering of putative signal
      peptides for the peptide length and the presence of an eight-residue hydrophobic
      patch and a typical signal peptidase cleavage site proved sufficient to eliminate
      the false-positive hits. Surprisingly, the results of this proteogenomics study,
      as well as a re-analysis of the E. coli genome with the latest version of SignalP
      program, show that the fraction of proteins containing signal peptides is only
      about 10%, or half of previous estimates.

PMID- 23556539
TI  - Refractory immune thrombocytopenia successfully treated with high-dose vitamin D
      supplementation and hydroxychloroquine: two case reports.
AB  - INTRODUCTION: Immune thrombocytopenic purpura is thought to be characterized by
      an immune response against the host's own platelets. If the thrombocytopenia is
      severe, patients are initially treated with high-dose steroids. Other more toxic
      second line treatments are considered if steroids fail. Here, we report the case
      of two patients in whom conventional treatment was unsuccessful but who responded
      to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of
      our knowledge, this is the first description of successful treatment for immune
      thrombocytopenia with high-dose vitamin D and hydroxychloroquine. CASE
      PRESENTATION: Case 1: We report the case of a 79-year-old Caucasian man who
      presented with high titer antinuclear antibodies, positive anti-SSA/Ro
      autoantibodies and clinically was felt to have an overlap of systemic lupus
      erythematosus and/or Sjogren's syndrome with profound life-threatening
      thrombocytopenia. There was no evidence of underlying malignancy. The patient's
      platelet count significantly increased with vitamin D and hydroxychloroquine
      treatment, but upon vitamin D discontinuation his platelet levels plummeted.
      Hydroxychloroquine therapy was maintained throughout treatment. With
      reinstitution of high-dose vitamin D therapy, platelet counts were restored to
      normal levels.Case 2: We also report the case of an 87-year-old Caucasian woman
      who presented with high titer antinuclear antibodies, positive anti-SSA/Ro
      autoantibodies and was felt to have an overlap of systemic lupus erythematosus
      and/or Sjogren's syndrome with immune thrombocytopenia; she also had severely low
      levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying
      malignancy. She responded to high-dose vitamin D replacement and
      hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid
      treatment. She remains in remission while taking vitamin D, hydroxychloroquine
      and very low-dose prednisone. No untoward side effects were observed in either
      patient. CONCLUSIONS: In our two case reports, we found an association between
      vitamin D deficiency and immune thrombocytopenia where platelet levels responded
      to vitamin D treatment and hydroxychloroquine but not to prednisone. We believe
      there may be synergism between vitamin D supplementation and hydroxychloroquine.
      The mechanism by which high-dose vitamin D results in increased platelet counts
      in immune thrombocytopenia patients is unknown. However, vitamin D has long been
      thought to play an immunomodulatory role, which may include a dampened immune
      response in patients with immune thrombocytopenia or other autoimmune diseases.

PMID- 23556540
TI  - Visible to near-infrared sensitization of silicon substrates via energy transfer
      from proximal nanocrystals: further insights for hybrid photovoltaics.
AB  - We provide a unified spectroscopic evidence of efficient energy transfer (ET)
      from optically excited colloidal nanocrystal quantum dots (NQDs) into Si
      substrates in a broad range of wavelengths: from visible (545 nm) to near
      infrared (800 nm). Chemical grafting of nanocrystals on hydrogenated Si surfaces
      is achieved via amine-modified carboxy-alkyl chain linkers, thus ensuring
      complete surface passivation and accurate NQD positioning. Time-resolved
      photoluminescence (PL) has been measured for a set of CdSe/ZnS and CdSeTe/ZnS
      NQDs of various sizes and compositions grafted on Si and SiO2 substrates. The
      measured acceleration of the PL decays on Si substrates is in good agreement with
      theoretical expectations based on the frequency-dependent dielectric properties
      of Si and NQD-Si separation distances. A comparative analysis reveals separate
      contributions to ET coming from the nonradiative (NRET) and radiative (RET)
      channels: NRET is a dominant mechanism for proximal NQDs in the middle of the
      visible range and becomes comparable with RET toward near-infrared wavelengths.
      The broad range over which the ET efficiency is estimated to be at the level of
      ~90% further supports the concept that hybrid nanocrystal/silicon thin-film
      photovoltaic devices could efficiently harvest solar energy across the entire
      spectrum of wavelengths.

PMID- 23556541
TI  - A pre-clinical functional assessment of an acellular scaffold intended for the
      treatment of hard-to-heal wounds.
AB  - The majority of the population experience successful wound-healing outcomes;
      however, 1-3% of those aged over 65 years experience delayed wound healing and
      wound perpetuation. These hard-to-heal wounds contain degraded and dysfunctional
      extracellular matrix (ECM); yet, the integrity of this structure is critical in
      the processes of normal wound healing. Here, we evaluated a novel synthetic
      matrix protein for its ability to act as an acellular scaffold that could replace
      dysfunctional ECM. In this regard, the synthetic protein was subjected to
      adsorption and diffusion assays using collagen and human dermal tissues;
      evaluated for its ability to influence keratinocyte and fibroblast attachment,
      migration and proliferation and assessed for its ability to influence in vivo
      wound healing in a porcine model. Critically, these experiments demonstrate that
      the matrix protein adsorbed to collagen and human dermal tissue but did not
      diffuse through human dermal tissue within a 24-hour observation period, and
      facilitated cell attachment, migration and proliferation. In a porcine wound
      healing model, significantly smaller wound areas were observed in the test group
      compared with the control group following the third treatment. These data provide
      evidence that the synthetic matrix protein has the ability to function as an
      acellular scaffold for wound-healing purposes.

PMID- 23556542
TI  - Examining the interpersonal-psychological theory of suicide in an inpatient
      veteran sample.
AB  - Suicide among veterans is a pressing public health concern. The interpersonal
      psychological theory of suicide proposes that perceived burdensomeness and
      thwarted belongingness lead to suicidal desire, whereas the acquired capability
      for suicide leads to suicide attempt in the presence of suicidal desire (Joiner,
      2005). Two hypotheses derived from the interpersonal-psychological theory of
      suicide were tested in 185 veterans (96 women) entering inpatient psychiatric
      treatment. Burdensomeness and its interaction with belongingness significantly
      predicted current suicidal ideation. The three-way interaction between
      burdensomeness, belongingness, and acquired capability did not significantly
      predict number of past suicide attempts. Clinical implications and directions for
      future research are discussed.

PMID- 23556544
TI  - Reply to 'Medicolegal considerations in bisphosphonate-related osteonecrosis of
      the jaw'.

PMID- 23556543
TI  - Comparing short versions of the AUDIT in a community-based survey of young
      people.
AB  - BACKGROUND: The 10-item Alcohol Use Disorders Identification Test (AUDIT-10) is
      commonly used to monitor harmful alcohol consumption among high-risk groups,
      including young people. However, time and space constraints have generated
      interest for shortened versions. Commonly used variations are the AUDIT-C (three
      questions) and the Fast Alcohol Screening Test (FAST) (four questions), but their
      utility in screening young people in non-clinical settings has received little
      attention. METHODS: We examined the performance of established and novel
      shortened versions of the AUDIT in relation to the full AUDIT-10 in a community
      based survey of young people (16-29 years) attending a music festival in
      Melbourne, Australia (January 2010).Among those reporting drinking alcohol in the
      previous 12 months, the following statistics were systematically assessed for all
      possible combinations of three or four AUDIT items and established AUDIT
      variations: Cronbach's alpha (internal consistency), variance explained (R2) and
      Pearson's correlation coefficient (concurrent validity). For our purposes, novel
      shortened AUDIT versions considered were required to represent all three AUDIT
      domains and include item 9 on alcohol-related injury. RESULTS: We recruited 640
      participants (68% female) reporting drinking in the previous 12 months. Median
      AUDIT-10 score was 10 in males and 9 in females, and 127 (20%) were classified as
      having at least high-level alcohol problems according to WHO classification.The
      FAST scored consistently high across statistical measures; it explained 85.6% of
      variance in AUDIT-10, correlation with AUDIT-10 was 0.92, and Cronbach's alpha
      was 0.66. A number of novel four-item AUDIT variations scored similarly high.
      Comparatively, the AUDIT-C scored substantially lower on all measures except
      internal consistency. CONCLUSIONS: Numerous abbreviated variations of the AUDIT
      may be a suitable alternative to the AUDIT-10 for classifying high-level alcohol
      problems in a community-based population of young Australians. Four-item AUDIT
      variations scored more consistently high across all evaluated statistics compared
      to three-item combinations. Novel AUDIT versions may be more effective than many
      established shortened versions as an alternative screening tool to the AUDIT-10
      to measure hazardous or harmful alcohol consumption in this population.

PMID- 23556545
TI  - Reduced adhesion of oral bacteria on hydroxyapatite by fluoride treatment.
AB  - The mechanisms of action of fluoride have been discussed controversially for
      decades. The cavity-preventive effect for teeth is often traced back to effects
      on demineralization. However, an effect on bacterial adhesion was indicated by
      indirect macroscopic studies. To characterize adhesion on fluoridated samples on
      a single bacterial level, we used force spectroscopy with bacterial probes to
      measure adhesion forces directly. We tested the adhesion of Streptococcus mutans
      , Streptococcus oralis , and Staphylococcus carnosus on smooth, high-density
      hydroxyapatite surfaces, pristine and after treatment with fluoride solution. All
      bacteria species exhibit lower adhesion forces after fluoride treatment of the
      surfaces. These findings suggest that the decrease of adhesion properties is a
      further key factor for the cariostatic effect of fluoride besides the decrease of
      demineralization.

PMID- 23556546
TI  - The influence of the use of diagnostic resources on nurses' communication with
      simulated patients during admission interviews.
AB  - PURPOSE: The aim of this study was to determine how the use of diagnostic
      resources influences nurses' communication during admission interviews. METHODS:
      A randomized controlled trial was performed. Actors simulated patients based on
      case studies. We analyzed transcriptions of 60 interviews and video recordings
      using the Roter Method of Interaction Process Analysis. FINDINGS: Nurses mainly
      asked closed-ended questions. The use of knowledge sources, such as forms in the
      PES format or an assessment format, affected communication significantly in
      several aspects. CONCLUSION: Prestructured forms may promote comprehensive
      interviews, but nurses need to be aware that using certain kinds of diagnostic
      resources may hinder them from asking open-ended questions. PRACTICE
      IMPLICATIONS: Nurses need to increase their use of open-ended questions.

PMID- 23556547
TI  - Complete homozygous deletion of CTSC in an Iranian family with Papillon-Lefevre
      syndrome.

PMID- 23556548
TI  - Multiple-antigen ELISA for melioidosis--a novel approach to the improved
      serodiagnosis of melioidosis.
AB  - BACKGROUND: Burkholderia pseudomallei, the causative agent of melioidosis, is
      endemic to Southeast Asia and northern Australia. Clinical manifestations of
      disease are diverse, ranging from chronic infection to acute septicaemia. The
      current gold standard of diagnosis involves bacterial culture and identification
      which is time consuming and often too late for early medical intervention. Hence,
      rapid diagnosis of melioidosis is crucial for the successful management of
      melioidosis. METHODS: The study evaluated 4 purified B. pseudomallei recombinant
      proteins (TssD-5, Omp3, smBpF4 and Omp85) as potential diagnostic agents for
      melioidosis. A total of 68 sera samples from Malaysian melioidosis patients were
      screened for the presence of specific antibodies towards these proteins using
      enzyme-linked immunosorbent assay (ELISA). Sera from patients with various
      bacterial and viral infections but negative for B. pseudomallei, as well as sera
      from healthy individuals, were also included as non-melioidosis controls. The
      Mann Whitney test was performed to compare the statistical differences between
      melioidosis patients and the non-melioidosis controls. RESULTS: TssD-5
      demonstrated the highest sensitivity of 71% followed by Omp3 (59%), smBpF4 (41%)
      and Omp85 (19%). All 4 antigens showed equally high specificity (89-96%). A
      cocktail of all 4 antigens resulted in slightly reduced sensitivity of 65% but
      improved specificity (99%). Multiple-antigen ELISA provided improved sensitivity
      of 88.2% whilst retaining good specificity (96%). There was minimal reactivity
      with sera from healthy individuals proposing the utility of these antigens to
      demarcate diseased from non-symptomatic individuals in an endemic country.
      CONCLUSIONS: TssD-5 demonstrated high detection sensitivity and specificity and
      the results were obtained within a few hours compared to time consuming culture
      and IFAT methods commonly used in a clinical setting. The use of multiple
      antigens resulted in improved sensitivity (88.2%) whilst maintaining superior
      specificity. These data highlight the use of TssD-5 and other recombinant
      antigens tested in this study as potential serodiagnostic agents for melioidosis.

PMID- 23556549
TI  - Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study
      (SNAP).
AB  - BACKGROUND: Paracetamol (acetaminophen) poisoning remains the commonest cause of
      acute liver injury in Europe and North America. The intravenous (IV) N
      acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively
      unchanged. This involves 3 different infusion regimens (dose and time) lasting
      over 20 hours. The same weight-related dose of NAC is used irrespective of
      paracetamol dose. Complications include frequent nausea and vomiting,
      anaphylactoid reactions and dosing errors. We designed a randomised controlled
      study investigating the efficacy of antiemetic pre-treatment (ondansetron) using
      standard NAC and a modified, shorter, regimen. METHODS/DESIGN: We designed a
      double-blind trial using a 2 * 2 factorial design involving four parallel groups.
      Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and
      vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in
      paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was
      stratified on: paracetamol dose, perceived risk factors, and time to
      presentation. The primary outcome was the incidence of nausea and vomiting
      following NAC. In addition the frequency of anaphylactoid reactions and end of
      treatment liver function documented. Where clinically necessary further doses of
      NAC were administered as per standard UK protocols at the end of the first
      antidote course. DISCUSSION: This study is primarily designed to test the
      efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first
      attempt to formally examine new methods of administering IV NAC in paracetamol
      overdose. We anticipate, from volunteer studies, that nausea and vomiting will be
      less frequent with the new NAC regimen. In addition as anaphylactoid response
      appears related to plasma concentrations of both NAC and paracetamol
      anaphylactoid reactions should be less likely. This study is not powered to
      assess the relative efficacy of the two NAC regimens, however it will give useful
      information to power future studies. As the first formal randomised clinical
      trial in this patient group in over 30 years this study will also provide
      information to support further studies in patients in paracetamol overdose,
      particularly, when linked with modern novel biomarkers of liver damage, patients
      at different toxicity risk. TRIAL REGISTRATION: EudraCT number 2009-017800-10,
      ClinicalTrials.gov IdentifierNCT01050270.

PMID- 23556550
TI  - Polyamidoamine dendrimer impairs mitochondrial oxidation in brain tissue.
AB  - BACKGROUND: The potential nanocarrier polyamidoamine (PAMAM) generation 5 (G5
      NH(2)) dendrimer has been shown to evoke lasting neuronal depolarization and cell
      death in a concentration-dependent manner. In this study we explored the early
      progression of G5-NH(2) action in brain tissue on neuronal and astroglial cells.
      RESULTS: In order to describe early mechanisms of G5-NH(2) dendrimer action in
      brain tissue we assessed G5-NH(2) trafficking, free intracellular Ca(2+) and
      mitochondrial membrane potential (Psi(MITO)) changes in the rat hippocampal slice
      by microfluorimetry. With the help of fluorescent dye conjugated G5-NH(2), we
      observed predominant appearance of the dendrimer in the plasma membrane of
      pyramidal neurons and glial cells within 30 min. Under this condition, G5-NH(2)
      evoked robust intracellular Ca(2+) enhancements and Psi(MITO) depolarization both
      in pyramidal neurons and astroglial cells. Intracellular Ca(2+) enhancements
      clearly preceded Psi(MITO) depolarization in astroglial cells. Comparing
      activation dynamics, neurons and glia showed prevalence of lasting and transient
      Psi(MITO) depolarization, respectively. Transient as opposed to lasting Psi(MITO)
      changes to short-term G5-NH(2) application suggested better survival of
      astroglia, as observed in the CA3 stratum radiatum area. We also showed that
      direct effect of G5-NH(2) on astroglial Psi(MITO) was significantly enhanced by
      neuron-astroglia interaction, subsequent to G5-NH(2) evoked neuronal activation.
      CONCLUSION: These findings indicate that the interaction of the PAMAM dendrimer
      with the plasma membrane leads to robust activation of neurons and astroglial
      cells, leading to mitochondrial depolarization. Distinguishable dynamics of
      mitochondrial depolarization in neurons and astroglia suggest that the enhanced
      mitochondrial depolarization followed by impaired oxidative metabolism of neurons
      may be the primary basis of neurotoxicity.

PMID- 23556551
TI  - Second-line rescue triple therapy with levofloxacin after failure of non-bismuth
      quadruple "sequential" or "concomitant" treatment to eradicate H. pylori
      infection.
AB  - BACKGROUND: Non-bismuth quadruple "sequential" and "concomitant" regimens,
      including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a
      nitroimidazole, are increasingly used as first-line treatments for Helicobacter
      pylori infection. Eradication with rescue regimens may be challenging after
      failure of key antibiotics such as clarithromycin and nitroimidazoles. AIM: To
      evaluate the efficacy and tolerability of a second-line levofloxacin-containing
      triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori
      after non-bismuth quadruple-containing treatment failure. METHODS:  DESIGN:
      prospective multicenter study. PATIENTS: in whom a non-bismuth quadruple regimen,
      administered either sequentially (PPI + amoxicillin for 5 days followed by PPI +
      clarithromycin + metronidazole for 5 more days) or concomitantly (PPI +
      amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed.
      INTERVENTION: levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI
      (standard dose b.i.d.) for 10 days. OUTCOME: eradication was confirmed with (13)C
      urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance
      was determined through questioning and recovery of empty medication envelopes.
      Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS:
      100 consecutive patients were included (mean age 50 years, 62% females, 12%
      peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after
      "concomitant" treatment failure. All patients took all medications correctly.
      Overall, per-protocol and intention-to-treat H. pylori eradication rates were
      75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates
      for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%,
      respectively. Adverse effects were reported in six (6%) patients; all of them
      were mild. CONCLUSION: Ten-day levofloxacin-containing triple therapy constitutes
      an encouraging second-line strategy in patients with previous non-bismuth
      quadruple "sequential" or "concomitant" treatment failure.

PMID- 23556552
TI  - Craniocervical junction abnormalities in dogs.
AB  - Craniocervical junction abnormality (CJA) is a term that encompasses a number of
      developmental anatomical aberrations at the region of the caudal occiput and
      first two cervical vertebrae. Chiari-like malformation appears to be the most
      common CJA encountered in dogs, and there has been a tremendous amount of
      clinical investigation into this disorder in recent years. Other abnormalities in
      this region include atlanto-occipital overlap, dorsal constriction at C1/C2 and
      atlantoaxial instability. This review article presents an overview of the current
      understanding of CJA in dogs, as well as medical and surgical treatment options
      available.

PMID- 23556553
TI  - Clinical-surgical treatment of temporomandibular joint disorder in a psoriatic
      arthritis patient.
AB  - INTRODUCTION: Condylotomy is a surgical procedure that has been used as an option
      to treat temporomandibular disorder (TMD) patients. This technique has the
      advantage of avoiding intra-capsular alterations that might be found involving
      other surgical procedures. Its use, even when unilateral, has positive effect on
      treatment of both joints. METHODS: In order to better evaluate the benefits of a
      clinical-surgical treatment for TMD, the present report describes the case of a
      psoriatic arthritis patient. The case was clinically characterized by dental
      malloclusion, and imaging exams showed joint degeneration of the right mandibular
      condyle. The patient was treated by condylotomy technique after a prosthetic oral
      rehabilitation. RESULTS: No clinical-radiological signs or symptoms of
      progression of articular disease were observed within a period of 16 months after
      surgery. Furthermore, there was functional stability of the temporomandibular
      joint, total absence of local pain and improvement of mouth opening. CONCLUSION:
      The present study suggests that condylotomy can be considered as a valid option
      for the management of TMD, since it has low surgical morbidity and favorable
      clinical outcomes. In this case, the patient had a medical diagnosis of systemic
      disease presenting general pain and pain at the temporomandibular joint (TMJ), in
      addition of causal agent of TMD (dental malloclusion). The difficulty of finding
      a single etiology (malocclusion vs. systemic disease) did not exclude the
      indication of a clinical-surgical treatment to re-establish the balance of TMJ.

PMID- 23556554
TI  - Absolute pitch is associated with a large auditory digit span: a clue to its
      genesis.
AB  - Auditory and visual digit span tests were administered to a group of absolute
      pitch (AP) possessors, and a group of AP nonpossessors matched for age, and for
      age of onset and duration of musical training. All subjects were speakers of
      English. The AP possessors substantially and significantly outperformed the
      nonpossessors on the auditory test, while the two groups did not differ
      significantly on the visual test. It is conjectured that a large auditory memory
      span, including memory for speech sounds, facilitates the development of
      associations between pitches and their verbal labels early in life, so promoting
      the acquisition of AP.

PMID- 23556555
TI  - Prosodic boundary tone classification with voice quality features.
AB  - Voice quality features such as harmonic structure and spectral tilt are
      investigated in classifying vocalic segments into one of five boundary tones in
      the tones and break indices system. Static and nonstatic features are examined,
      and performance is compared with features related to duration, pitch, and
      amplitude, along with adjacent segment characteristics. From statistical tests,
      voice quality features are found to be significant for classifying prosodic
      boundary tones, and especially for distinguishing low-tone boundaries.
      Classification results using features selected from Kruskal-Wallis tests, Akaike
      information criterion values, and from sequential forward search show that using
      voice quality features leads to lower balanced error rates.

PMID- 23556556
TI  - Transient ultrasound propagation in porous media using Biot theory and fractional
      calculus: application to human cancellous bone.
AB  - A temporal model based on the Biot theory is developed to describe the transient
      ultrasonic propagation in porous media with elastic structure, in which the
      viscous exchange between fluid and structure are described by fractional
      derivatives. The fast and slow waves obey a fractional wave equation in the time
      domain. The solution of Biot's equations in time depends on the Green functions
      of each of the waves (fast and slow), and their fractional derivatives. The
      reflection and transmission operators for a slab of porous materials are derived
      in the time domain, using calculations in the Laplace domain. Their analytical
      expressions, depend on Green's function of fast and slow waves. Experimental
      results for slow and fast waves transmitted through human cancellous bone samples
      are given and compared with theoretical predictions.

PMID- 23556557
TI  - Sound scattering by a vortex dipole.
AB  - Sound scattering by a system of two counter-rotating vortices (Lamb dipole) is
      considered, using the effective approach of Pitaevskii [J. Exp. Theor. Phys
      (USSR) 35, 1271-1275 (1958); Sov. Phys. JETP 85, 888-890 (1959)], based on
      application of the asymptotic representation of the scattering Green function,
      the Dirac delta function modeling of the vortex, and the Fourier transformation
      of the vector of scattering. The sound frequency is supposed to be low. The
      directivity pattern of the radiation, scattered by the Lamb dipole is obtained.
      There is no singularity in scattering field in this case as it must be for the
      vorticity with zero circulation, so the dipole is a more appropriate object for
      the approximation used.

PMID- 23556558
TI  - Efficient finite element modeling of radiation forces on elastic particles of
      arbitrary size and geometry.
AB  - A finite element based method is presented for calculating the acoustic radiation
      force on arbitrarily shaped elastic and fluid particles. Importantly for future
      applications, this development will permit the modeling of acoustic forces on
      complex structures such as biological cells, and the interactions between them
      and other bodies. The model is based on a non-viscous approximation, allowing the
      results from an efficient, numerical, linear scattering model to provide the
      basis for the second-order forces. Simulation times are of the order of a few
      seconds for an axi-symmetric structure. The model is verified against a range of
      existing analytical solutions (typical accuracy better than 0.1%), including
      those for cylinders, elastic spheres that are of significant size compared to the
      acoustic wavelength, and spheroidal particles.

PMID- 23556559
TI  - Spin current-induced by a sound wave.
AB  - The interaction of conduction electrons with a longitudinal sound wave
      propagating in a crystal in a constant magnetic field is investigated. It is
      shown that the transverse spin current arises when the longitudinal sound wave
      propagation through the system. The average power absorbed by the spin subsystem
      of the conduction electrons and the spin-Hall conductivity have a resonant
      character.

PMID- 23556560
TI  - Breakup of finite thickness viscous shell microbubbles by ultrasound: a
      simplified zero-thickness shell model.
AB  - A simplified three-dimensional (3-D) zero-thickness shell model was developed to
      recover the non-spherical response of thick-shelled encapsulated microbubbles
      subjected to ultrasound excitation. The model was validated by comparison with
      previously developed models and was then used to study the mechanism of bubble
      break-up during non-spherical deformations resulting from the presence of a
      nearby rigid boundary. The effects of the shell thickness and the bubble standoff
      distance from the solid wall on the bubble break-up were studied parametrically
      for a fixed insonification frequency and amplitude. A diagram of bubble shapes
      versus the normalized shell thickness and wall standoff was derived, and the
      potential bubble shapes at break-up from reentrant jets were categorized
      resulting in four distinct zones.

PMID- 23556561
TI  - Exact solutions for sound radiation from a moving monopole above an impedance
      plane.
AB  - The acoustic field of a monopole source moving with constant velocity at constant
      height above an infinite locally reacting plane can be expressed in analytical
      form by combining the Lorentz transformation with the method of superimposing
      complex or real point sources. For a plane with masslike response, the solution
      in Lorentz space consists of a superposition of monopoles only and therefore,
      does not differ in principle from the solution for the corresponding stationary
      boundary value problem. However, by considering a frequency independent surface
      impedance, e.g., with pure absorbing behavior, the half-space Green's function is
      now comprised of not only a line of monopoles but also of dipoles. For certain
      field points at a special line g, this solution can be written explicitly by
      using an exponential integral. For arbitrary field points, the method of
      stationary phase leads to an asymptotic solution for the reflection coefficient
      which agrees with prior results from the literature.

PMID- 23556562
TI  - Evaluating a linearized Euler equations model for strong turbulence effects on
      sound propagation.
AB  - Sound propagation outdoors is strongly affected by atmospheric turbulence. Under
      strongly perturbed conditions or long propagation paths, the sound fluctuations
      reach their asymptotic behavior, e.g., the intensity variance progressively
      saturates. The present study evaluates the ability of a numerical propagation
      model based on the finite-difference time-domain solving of the linearized Euler
      equations in quantitatively reproducing the wave statistics under strong and
      saturated intensity fluctuations. It is the continuation of a previous study
      where weak intensity fluctuations were considered. The numerical propagation
      model is presented and tested with two-dimensional harmonic sound propagation
      over long paths and strong atmospheric perturbations. The results are compared to
      quantitative theoretical or numerical predictions available on the wave
      statistics, including the log-amplitude variance and the probability density
      functions of the complex acoustic pressure. The match is excellent for the
      evaluated source frequencies and all sound fluctuations strengths. Hence, this
      model captures these many aspects of strong atmospheric turbulence effects on
      sound propagation. Finally, the model results for the intensity probability
      density function are compared with a standard fit by a generalized gamma
      function.

PMID- 23556563
TI  - Point vortex model for prediction of sound generated by a wing with flap
      interacting with a passing vortex.
AB  - Acoustic signature of a rigid wing, equipped with a movable downstream flap and
      interacting with a line vortex, is studied in a two-dimensional low-Mach number
      flow. The flap is attached to the airfoil via a torsion spring, and the coupled
      fluid-structure interaction problem is analyzed using thin-airfoil methodology
      and application of the emended Brown and Michael equation. It is found that
      incident vortex passage above the airfoil excites flap motion at the system
      natural frequency, amplified above all other frequencies contained in the forcing
      vortex. Far-field radiation is analyzed using Powell-Howe analogy, yielding the
      leading order dipole-type signature of the system. It is shown that direct flap
      motion has a negligible effect on total sound radiation. The characteristic
      acoustic signature of the system is dominated by vortex sound, consisting of
      relatively strong leading and trailing edge interactions of the airfoil with the
      incident vortex, together with late-time wake sound resulting from induced flap
      motion. In comparison with the counterpart rigid (non-flapped) configuration, it
      is found that the flap may act as sound amplifier or absorber, depending on the
      value of flap-fluid natural frequency. The study complements existing analyses
      examining sound radiation in static- and detached-flap configurations.

PMID- 23556564
TI  - Analyzing sound speed fluctuations in shallow water from group-velocity versus
      phase-velocity data representation.
AB  - Data collected over more than eight consecutive hours between two source-receiver
      arrays in a shallow water environment are analyzed through the physics of the
      waveguide invariant. In particular, the use of vertical arrays on both the source
      and receiver sides provides source and receiver angles in addition to travel
      times associated with a set of eigenray paths in the waveguide. From the travel
      times and the source-receiver angles, the eigenrays are projected into a group
      velocity versus phase-velocity (Vg-Vp) plot for each acquisition. The time
      evolution of the Vg-Vp representation over the 8.5-h long experiment is
      discussed. Group speed fluctuations observed for a set of eigenrays with turning
      points at different depths in the water column are compared to the Brunt-Vaisala
      frequency.

PMID- 23556565
TI  - Nonuniform depth grids in parabolic equation solutions.
AB  - The parabolic wave equation is solved using a finite-difference solution in depth
      that involves a nonuniform grid. The depth operator is discretized using
      Galerkin's method with asymmetric hat functions. Examples are presented to
      illustrate that this approach can be used to improve efficiency for problems in
      ocean acoustics and seismo-acoustics. For shallow water problems, accuracy is
      sensitive to the precise placement of the ocean bottom interface. This issue is
      often addressed with the inefficient approach of using a fine grid spacing over
      all depth. Efficiency may be improved by using a relatively coarse grid with
      nonuniform sampling to precisely position the interface. Efficiency may also be
      improved by reducing the sampling in the sediment and in an absorbing layer that
      is used to truncate the computational domain. Nonuniform sampling may also be
      used to improve the implementation of a single-scattering approximation for
      sloping fluid-solid interfaces.

PMID- 23556566
TI  - Using multi-frequency acoustic attenuation to monitor grain size and
      concentration of suspended sediment in rivers.
AB  - Multi-frequency acoustic backscatter profiles recorded with side-looking acoustic
      Doppler current profilers are used to monitor the concentration and size of
      sedimentary particles suspended in fluvial environments. Data at 300, 600, and
      1200 kHz are presented from the Isere River in France where the dominant
      particles in suspension are silt and clay sizes. The contribution of suspended
      sediment to the through-water attenuation was determined for three high
      concentration (> 100 mg/L) events and compared to theoretical values for
      spherical particles having size distributions that were measured by laser
      diffraction in water samples. Agreement was good for the 300 kHz data, but it
      worsened with increasing frequency. A method for the determination of grain size
      using multi-frequency attenuation data is presented considering models for
      spherical and oblate spheroidal particles. When the resulting size estimates are
      used to convert sediment attenuation to concentration, the spheroidal model
      provides the best agreement with optical estimates of concentration, but the
      aspect ratio and grain size that provide the best fit differ between events. The
      acoustic estimates of size were one-third the values from laser grain sizing.
      This agreement is encouraging considering optical and acoustical instruments
      measure different parameters.

PMID- 23556567
TI  - Underwater radiated noise levels of a research icebreaker in the central Arctic
      Ocean.
AB  - U.S. Coast Guard Cutter Healy's underwater radiated noise signature was
      characterized in the central Arctic Ocean during different types of ice-breaking
      operations. Propulsion modes included transit in variable ice cover, breaking
      heavy ice with backing-and-ramming maneuvers, and dynamic positioning with the
      bow thruster in operation. Compared to open-water transit, Healy's noise
      signature increased approximately 10 dB between 20 Hz and 2 kHz when breaking
      ice. The highest noise levels resulted while the ship was engaged in backing-and
      ramming maneuvers, owing to cavitation when operating the propellers astern or in
      opposing directions. In frequency bands centered near 10, 50, and 100 Hz, source
      levels reached 190-200 dB re: 1 MUPa at 1 m (full octave band) during ice
      breaking operations.

PMID- 23556568
TI  - Acoustic observations of internal tides and tidal currents in shallow water.
AB  - Significant acoustic travel-time variability and frequency shifts of acoustic
      intensity level curves in broadband signal spectrograms were measured in the East
      China Sea during the summer of 2008. The broadband pulses (270-330 Hz) were
      transmitted from a fixed source and received at a bottomed horizontal array,
      located at the 33 km range. The acoustic intensity level curves of the received
      signals indicate regular frequency shifts that are well correlated with the
      measured internal tides. Similarly, regular travel-time shifts of the acoustic
      mode arrivals correlate well with the barotropic tides and can be explained by
      tidal currents along the acoustic propagation track. These observations indicate
      the potential of monitoring internal tides and tidal currents using low-frequency
      acoustic signals propagating at long ranges.

PMID- 23556569
TI  - Azimuth-elevation direction finding using a microphone and three orthogonal
      velocity sensors as a non-collocated subarray.
AB  - An acoustic vector-sensor consists of three identical but orthogonally oriented
      acoustic particle-velocity sensors, plus a pressure sensor-all spatially
      collocated in a point-like geometry. At any point in space, this tri-axial
      acoustic vector-sensor can sample an acoustic wavefield as a 3 * 1 vector,
      instead of simply as a scalar of pressure. This vector, after proper self
      normalization, would indicate the incident wave-field's propagation direction,
      and thus the incident emitter's azimuth-elevation direction-of-arrival. This
      "self-normalization" direction-of-arrival estimator is predicated on the spatial
      collocation among the three particle-velocity sensors and the pressure-sensor.
      This collocation constriction is relaxed here by this presently proposed idea, to
      realize a spatially distributed acoustic vector-sensor, allowing its four
      component-sensors to be separately located. This proposed scheme not only retains
      the algorithmic advantages of the aforementioned "self-normalization" direction
      of-arrival estimator, but also will significantly extend the spatial aperture to
      improve the direction-finding accuracy by orders of magnitude.

PMID- 23556570
TI  - Impact of polydispersity on multipolar resonant scattering in emulsions.
AB  - The influence of size polydispersity on the resonant acoustic properties of
      dilute emulsions, made of fluorinated-oil droplets, is quantitatively
      investigated. Ultrasound attenuation and dispersion measurements on various
      samples with controlled size polydispersities, ranging from 1% to 13%, are found
      to be in excellent agreement with predictions based on the independent scattering
      approximation. By relating the particle-size distribution of the synthesized
      emulsions to the quality factor of the predicted multipolar resonances, the
      number of observable acoustic resonances is shown to be imposed by the sample
      polydispersity. These results are briefly discussed into the context of
      metamaterials for which scattering resonances are central to their effective
      properties.

PMID- 23556571
TI  - Nusselt numbers of laminar, oscillating flows in stacks and regenerators with
      pores of arbitrary cross-sectional geometry.
AB  - Though widely used in steady-flow heat transfer applications, the Nusselt number
      a dimensionless heat transfer coefficient-has not been studied as thoroughly in
      oscillating flows and is therefore not generally used in thermoacoustic
      applications. This paper presents expressions for the Nusselt numbers of laminar
      oscillating flows within the pores of stacks and regenerators, derived from
      thermoacoustic theory developed by Rott and Swift. These expressions are based on
      bulk (velocity-weighted, cross-sectionally averaged) temperature, rather than the
      cross-sectionally averaged temperature. Results are shown for parallel plates,
      circular pores, rectangular pores, and within the boundary layer limit. It is
      shown that bulk temperature does not become infinite during an acoustic cycle and
      that the Nusselt number is a complex constant at all times. In addition, steady
      flow Nusselt numbers are recovered when velocity and temperature profiles are
      like those in steady flows.

PMID- 23556572
TI  - Synthetic aperture flow imaging using dual stage beamforming: simulations and
      experiments.
AB  - A method for synthetic aperture flow imaging using dual stage beamforming has
      been developed. The main motivation is to increase the frame rate and still
      maintain a beamforming quality sufficient for flow estimation that is possible to
      implement in a commercial scanner. This method can generate continuous high frame
      rate flow images with lower calculation demands than the full synthetic aperture
      flow imaging. The performance of the approach was investigated using Field II
      simulations and measurements with the experimental scanner SARUS. A laminar flow
      with a parabolic profile was generated by a flow rig system. The flow data were
      acquired by a commercial 7 MHz linear array transducer. Four emissions were
      transmitted sequentially and repeated 12 times corresponding to 48 emissions.
      Flow with a peak velocity of 0.12 m/s was measured, the relative standard
      deviation was 6.4%, and the bias was 7.6% (2.1% and 3.2% for the simulations). A
      parameter study revealed that emission spacing, number of cross-correlation
      functions used for averaging, and the length of the velocity searching range
      influence the performance. Compared to the full synthetic aperture flow imaging
      the total number of beamformed samples are reduced by a factor of 64 times, and
      the frame rate is much higher than the conventional method for the same velocity
      estimation accuracy.

PMID- 23556573
TI  - Transient axial solution for plane and axisymmetric waves focused by a
      paraboloidal reflector.
AB  - A time domain analytical solution is presented to calculate the pressure response
      along the axis of a paraboloidal reflector for a normally incident plane wave.
      This work is inspired by Hamilton's axial solution for an ellipsoidal mirror and
      the same methodology is employed in this paper. Behavior of the reflected waves
      along reflector axis is studied, and special interest is placed on focusing gain
      obtained at the focal point. This analytical solution indicates that the focusing
      gain is affected by reflector geometry and the time derivative of the input
      signal. In addition, focused pressure response in the focal zone given by various
      reflector geometries and input frequencies are also investigated. This
      information is useful for selecting appropriate reflector geometry in a specific
      working environment to achieve the best signal enhancement. Numerical simulation
      employing the finite element method is used to validate the analytical solution,
      and visualize the wave field to provide a better understanding of the propagation
      of reflected waves. This analytical solution can be modified to apply to non
      planar incident waves with axisymmetric wavefront and non-uniform pressure
      distribution. An example of incident waves with conical-shaped wavefront is
      presented.

PMID- 23556574
TI  - Refined acoustic modeling and analysis of shotgun microphones.
AB  - A shotgun microphone is a highly directional pickup device widely used in noisy
      environments. The key element that leads to its superior directivity is a tube
      with multiple slot openings along its length. One traditional way to model the
      directional response of a shotgun is to assume plane waves traveling in the tube
      as if it is in the free field. However, the frequency response and directivity
      predicted by this traveling wave model can differ drastically from practical
      measurements. In this paper, an in-depth electroacoustic analysis was conducted
      to examine the problem by considering the standing waves inside the tube with an
      analogous circuit containing phased pressure sources and T-networks of tube
      segments. A further refinement is to model the housing diffraction effect with
      the aid of the equivalent source method (ESM). The on-axis frequency response and
      directivity pattern predicted by the proposed model are in close agreement with
      the measurements. From the results, a peculiar bifurcation phenomenon of
      directivity pattern at the Helmholtz frequency was also noted. While the shotgun
      behaves like an endfire array above the Helmholtz frequency, it becomes a
      broadside array below the Helmholtz frequency. The standing wave effect can be
      mitigated by covering the slot openings with mesh screen, which was found to
      alter the shotgun response to be closer to that of the traveling wave model above
      a critical frequency predicted by the half-wavelength rule. A mode-switching
      model was developed to predict the directional responses of mesh-treated
      shotguns.

PMID- 23556575
TI  - Experimental validation of sound field control with a circular double-layer array
      of loudspeakers.
AB  - This paper is concerned with experimental validation of a recently proposed
      method of controlling sound fields with a circular double-layer array of
      loudspeakers [Chang and Jacobsen, J. Acoust. Soc. Am. 131(6), 4518-4525 (2012)].
      The double-layer of loudspeakers is realized with 20 pairs of closed-box
      loudspeakers mounted back-to-back. Source strengths are obtained with several
      solution methods by modeling loudspeakers as a weighted combination of monopoles
      and dipoles. Sound pressure levels of the controlled sound fields are measured
      inside and outside the array in an anechoic room, and performance indices are
      calculated. The experimental results show that a method of combining pure
      contrast maximization with a pressure matching technique provides only a small
      error in the listening zone between the desired and the reproduced fields, and at
      the same time reduces the sound level in the quiet zone as expected in the
      simulation studies well above the spatial Nyquist frequency except at a few
      frequencies. It is also shown that errors in the positions of the loudspeakers
      can be critical to the results at frequencies where the distance between the
      inner and the outer array is close to half a wavelength.

PMID- 23556576
TI  - Sound localization in individualized and non-individualized crosstalk
      cancellation systems.
AB  - The sound-source localization provided by a crosstalk cancellation (CTC) system
      depends on the head-related transfer functions (HRTFs) used for the CTC filter
      calculation. In this study, the horizontal- and sagittal-plane localization
      performance was investigated in humans listening to individualized matched,
      individualized but mismatched, and non-individualized CTC systems. The systems
      were simulated via headphones in a binaural virtual environment with two virtual
      loudspeakers spatialized in front of the listener. The individualized mismatched
      system was based on two different sets of listener-individual HRTFs. Both sets
      provided similar binaural localization performance in terms of quadrant, polar,
      and lateral errors. The individualized matched systems provided performance
      similar to that from the binaural listening. For the individualized mismatched
      systems, the performance deteriorated, and for the non-individualized mismatched
      systems (based on HRTFs from other listeners), the performance deteriorated even
      more. The direction-dependent analysis showed that mismatch and lack of
      individualization yielded a substantially degraded performance for targets placed
      outside of the loudspeaker span and behind the listeners, showing relevance of
      individualized CTC systems for those targets. Further, channel separation was
      calculated for different frequency ranges and is discussed in the light of its
      use as a predictor for the localization performance provided by a CTC system.

PMID- 23556577
TI  - Prediction of high-frequency vibration transmission across coupled, periodic
      ribbed plates by incorporating tunneling mechanisms.
AB  - Prediction of structure-borne sound transmission on built-up structures at audio
      frequencies is well-suited to Statistical Energy Analysis (SEA) although the
      inclusion of periodic ribbed plates presents challenges. This paper considers an
      approach using Advanced SEA (ASEA) that can incorporate tunneling mechanisms
      within a statistical approach. The coupled plates used for the investigation form
      an L-junction comprising a periodic ribbed plate with symmetric ribs and an
      isotropic homogeneous plate. Experimental SEA (ESEA) is carried out with input
      data from Finite Element Methods (FEM). This indicates that indirect coupling is
      significant at high frequencies where bays on the periodic ribbed plate can be
      treated as individual subsystems. SEA using coupling loss factors from wave
      theory leads to significant underestimates in the energy of the bays when the
      isotropic homogeneous plate is excited. This is due to the absence of tunneling
      mechanisms in the SEA model. In contrast, ASEA shows close agreement with FEM and
      laboratory measurements. The errors incurred with SEA rapidly increase as the
      bays become more distant from the source subsystem. ASEA provides significantly
      more accurate predictions by accounting for the spatial filtering that leads to
      non-diffuse vibration fields on these more distant bays.

PMID- 23556578
TI  - Underwater sound scattering and absorption by a coated infinite plate with a
      distributed inhomogeneity.
AB  - This paper concerns itself with the scattering and absorption of underwater
      incident sound by a coated infinite plate with an attached distributed
      inhomogeneity. Its objective is to determine if the distributed inhomogeneity can
      provide additional local reflection, such that it only increases the signal-to
      noise ratio for a hydrophone detector placed on the inhomogeneity without
      significantly decreasing the overall sound absorption of the coated plate.

PMID- 23556579
TI  - An acoustic inverse scattering problem for spheres with radially inhomogeneous
      compressibility.
AB  - An inverse acoustic scattering problem the main aim of which is to reconstruct
      the one-dimensional variation of the acoustical parameters of a spherical object
      is investigated. The problem is first formulated conventionally through a coupled
      system of integral equations, and then this system is reduced to one-dimensional
      form by using the orthogonality properties of spherical harmonics. The inverse
      problem is solved in an iterative fashion via classical Newton algorithm. Some
      numerical simulations are carried out to test the feasibility of the method as
      well as to see the effects of some parameters on the solution. It is shown that
      the method is very effective for the profiles having smooth variations provided
      that an appropriate initial guess is chosen. However, some of the classical
      disadvantages of the Newton type algorithms are also observed in numerical
      experiments which may limit the applicability of the method to a certain extent.

PMID- 23556580
TI  - Multi-channel Kalman filters for active noise control.
AB  - By formulating the feed-forward broadband active noise control problem as a state
      estimation problem it is possible to achieve a faster rate of convergence than
      the filtered reference least mean squares algorithm and possibly also a better
      tracking performance. A multiple input/multiple output Kalman algorithm is
      derived to perform this state estimation. To make the algorithm more suitable for
      real-time applications, the Kalman filter is written in a fast array form and the
      secondary path state matrices are implemented in output normal form. The
      resulting filter implementation is tested in simulations and in real-time
      experiments. It was found that for a constant primary path the filter has a fast
      rate of convergence and is able to track changes in the frequency spectrum. For a
      forgetting factor equal to unity the system is robust but the filter is unable to
      track rapid changes in the primary path. A forgetting factor lower than 1 gives a
      significantly improved tracking performance but leads to a numerical instability
      for the fast array form of the algorithm.

PMID- 23556581
TI  - Similarity spectra analysis of high-performance jet aircraft noise.
AB  - Noise measured in the vicinity of an F-22A Raptor has been compared to similarity
      spectra found previously to represent mixing noise from large-scale and fine
      scale turbulent structures in laboratory-scale jet plumes. Comparisons have been
      made for three engine conditions using ground-based sideline microphones, which
      covered a large angular aperture. Even though the nozzle geometry is complex and
      the jet is nonideally expanded, the similarity spectra do agree with large
      portions of the measured spectra. Toward the sideline, the fine-scale similarity
      spectrum is used, while the large-scale similarity spectrum provides a good fit
      to the area of maximum radiation. Combinations of the two similarity spectra are
      shown to match the data in between those regions. Surprisingly, a combination of
      the two is also shown to match the data at the farthest aft angle. However, at
      high frequencies the degree of congruity between the similarity and the measured
      spectra changes with engine condition and angle. At the higher engine conditions,
      there is a systematically shallower measured high-frequency slope, with the
      largest discrepancy occurring in the regions of maximum radiation.

PMID- 23556582
TI  - Combined effect of noise and vibration produced by high-speed trains on annoyance
      in buildings.
AB  - The effects of noise and vibration on annoyance in buildings during the passage
      of a nearby high-speed train have been investigated in a laboratory experiment
      with recorded train noise and 20 Hz vibration. The noises included the effects of
      two types of facade: windows-open and windows-closed. Subjects were exposed to
      six levels of noise and six magnitudes of vibration, and asked to rate annoyance
      using an 11-point numerical scale. The experiment consisted of four sessions: (1)
      evaluation of noise annoyance in the absence of vibration, (2) evaluation of
      total annoyance from simultaneous noise and vibration, (3) evaluation of noise
      annoyance in the presence of vibration, and (4) evaluation of vibration annoyance
      in the absence of noise. The results show that vibration did not influence
      ratings of noise annoyance, but that total annoyance caused by combined noise and
      vibration was considerably greater than the annoyance caused by noise alone. The
      noise annoyance and the total annoyance caused by combined noise and vibration
      were associated with subject self-ratings of noise sensitivity. Two classical
      models of total annoyance due to combined noise sources (maximum of the single
      source annoyance or the integration of individual annoyance ratings) provided
      useful predictions of the total annoyance caused by simultaneous noise and
      vibration.

PMID- 23556583
TI  - Acoustic methods for measuring the porosities of porous materials incorporating
      dead-end pores.
AB  - The acoustic properties of porous materials containing dead-end (DE) pores have
      been proposed by Dupont et al. [J. Appl. Phys. 110, 094903 (2011)]. In the
      theoretical description, two physical parameters were defined (the dead-end
      porosity and the average length of the dead-end pores). With the knowledge of the
      open porosity (measured with non-acoustic methods), and the measurement of
      kinematic porosity (also called the Biot porosity in this article), it is
      possible to deduce the dead-end porosity. Two acoustic methods for measuring the
      Biot porosity for a wide range of porosities are proposed. These methods are
      based on acoustic transmission and on the low and high frequency behaviors of
      acoustic indicators. The low frequency method is valid for high porosities. It
      involves measurements in a transmission tube and the knowledge of the theoretical
      asymptotic behavior of the phase velocity at high frequencies. The high frequency
      method is based on ultrasonic measurements and on the high frequency asymptotic
      behavior of the transmission coefficient. It is well adapted for material with
      relatively low values of porosity. Good precision was found for both methods and
      materials containing dead end porosity were tested.

PMID- 23556584
TI  - Room acoustics analysis using circular arrays: an experimental study based on
      sound field plane-wave decomposition.
AB  - Plane-wave decomposition (PWD) methods using microphone arrays have been shown to
      be a very useful tool within the applied acoustics community for their multiple
      applications in room acoustics analysis and synthesis. While many theoretical
      aspects of PWD have been previously addressed in the literature, the practical
      advantages of the PWD method to assess the acoustic behavior of real rooms have
      been barely explored so far. In this paper, the PWD method is employed to analyze
      the sound field inside a selected set of real rooms having a well-defined
      purpose. To this end, a circular microphone array is used to capture and process
      a number of impulse responses at different spatial positions, providing angle
      dependent data for both direct and reflected wavefronts. The detection of
      reflected plane waves is performed by means of image processing techniques
      applied over the raw array response data and over the PWD data, showing the
      usefulness of image-processing-based methods for room acoustics analysis.

PMID- 23556585
TI  - Development of a hybrid wave based-transfer matrix model for sound transmission
      analysis.
AB  - In this paper, a hybrid wave based-transfer matrix model is presented that allows
      for the investigation of the sound transmission through finite multilayered
      structures placed between two reverberant rooms. The multilayered structure may
      consist of an arbitrary configuration of fluid, elastic, or poro-elastic layers.
      The field variables (structural displacements and sound pressures) are expanded
      in terms of structural and acoustic wave functions. The boundary and continuity
      conditions in the rooms determine the participation factors in the pressure
      expansions. The displacement of the multilayered structure is determined by the
      mechanical impedance matrix, which gives a relation between the pressures and
      transverse displacements at both sides of the structure. The elements of this
      matrix are calculated with the transfer matrix method. First, the hybrid model is
      numerically validated. Next a comparison is made with sound transmission loss
      measurements of a hollow brick wall and a sandwich panel. Finally, numerical
      simulations show the influence of structural damping, room dimensions and plate
      dimensions on the sound transmission loss of multilayered structures.

PMID- 23556586
TI  - Time and frequency constrained sonar signal design for optimal detection of
      elastic objects.
AB  - In this paper, the task of model-based transmit signal design for optimizing
      detection is considered. Building on past work that designs the spectral
      magnitude for optimizing detection, two methods for synthesizing minimum duration
      signals with this spectral magnitude are developed. The methods are applied to
      the design of signals that are optimal for detecting elastic objects in the
      presence of additive noise and self-noise. Elastic objects are modeled as linear
      time-invariant systems with known impulse responses, while additive noise (e.g.,
      ocean noise or receiver noise) and acoustic self-noise (e.g., reverberation or
      clutter) are modeled as stationary Gaussian random processes with known power
      spectral densities. The first approach finds the waveform that preserves the
      optimal spectral magnitude while achieving the minimum temporal duration. The
      second approach yields a finite-length time-domain sequence by maximizing
      temporal energy concentration, subject to the constraint that the spectral
      magnitude is close (in a least-squares sense) to the optimal spectral magnitude.
      The two approaches are then connected analytically, showing the former is a
      limiting case of the latter. Simulation examples that illustrate the theory are
      accompanied by discussions that address practical applicability and how one might
      satisfy the need for target and environmental models in the real-world.

PMID- 23556587
TI  - Multipath correlations in underwater acoustic communication channels.
AB  - Uncorrelated scattering (US), which assumes that multipath arrivals undergo
      uncorrelated scattering and are thus uncorrelated, has been the standard model
      for digital communications including underwater acoustic communications. This
      paper examines the cross-correlation of multipath arrivals based on at-sea data
      with different temporal coherence time, assuming quasi-stationary statistics. It
      is found that multipath arrivals are highly cross-correlated when the channel is
      temporally coherent, and are uncorrelated when the channel is temporally
      incoherent. A theoretical model based on the path phase rates and relative-phase
      fluctuations is used to explain experimentally observed phenomena, assuming the
      path amplitudes vary slowly compared with the phases. The implications of
      correlated scattering for underwater acoustic communication channel tracking are
      discussed.

PMID- 23556588
TI  - Sparse-representation algorithms for blind estimation of acoustic-multipath
      channels.
AB  - Acoustic channel estimation is an important problem in various applications.
      Unlike many existing channel estimation techniques that need known probe or
      training signals, this paper develops a blind multipath channel identification
      algorithm. The proposed approach is based on the single-input multiple-output
      model and exploits the sparse multichannel structure. Three sparse representation
      algorithms, namely, matching pursuit, orthogonal matching pursuit, and basis
      pursuit, are applied to the blind sparse identification problem. Compared with
      the classical least squares approach to blind multichannel estimation, the
      proposed scheme does not require that the channel order be exactly determined and
      it is robust to channel order selection. Moreover, the ill-conditioning induced
      by the large delay spread is overcome by the sparse constraint. Simulation
      results for deconvolution of both underwater and room acoustic channels confirm
      the effectiveness of the proposed approach.

PMID- 23556589
TI  - Vector intensity reconstruction using the data completion method.
AB  - This paper presents an application of the data completion method (DCM) for vector
      intensity reconstructions. A mobile array of 36 pressure-pressure probes (72
      microphones) is used to perform measurements near a planar surface. Nevertheless,
      since the proposed method is based on integral formulations, DCM can be applied
      with any kind of geometry. This method requires the knowledge of Cauchy data
      (pressure and velocity) on a part of the boundary of an empty domain in order to
      evaluate pressure and velocity on the remaining part of the boundary. Intensity
      vectors are calculated in the interior domain surrounded by the measurement
      array. This inverse acoustic problem requires the use of a regularization method
      to obtain a realistic solution. An experiment in a closed wooden car trunk mock
      up excited by a shaker and two loudspeakers is presented. In this case, where the
      volume of the mock-up is small (0.61 m(3)), standing-waves and fluid structure
      interactions appear and show that DCM is a powerful tool to identify sources in a
      confined space.

PMID- 23556590
TI  - Inner-ear sound pressures near the base of the cochlea in chinchilla: further
      investigation.
AB  - The middle-ear pressure gain GMEP, the ratio of sound pressure in the cochlear
      vestibule PV to sound pressure at the tympanic membrane PTM, is a descriptor of
      middle-ear sound transfer and the cochlear input for a given stimulus in the ear
      canal. GMEP and the cochlear partition differential pressure near the cochlear
      base DeltaPCP, which determines the stimulus for cochlear partition motion and
      has been linked to hearing ability, were computed from simultaneous measurements
      of PV, PTM, and the sound pressure in scala tympani near the round window PST in
      chinchilla. GMEP magnitude was approximately 30 dB between 0.1 and 10 kHz and
      decreased sharply above 20 kHz, which is not consistent with an ideal transformer
      or a lossless transmission line. The GMEP phase was consistent with a roughly 50
      MUs delay between PV and PTM. GMEP was little affected by the inner-ear
      modifications necessary to measure PST. GMEP is a good predictor of DeltaPCP at
      low and moderate frequencies where PV >> PST but overestimates DeltaPCP above a
      few kilohertz where PV ~ PST. The ratio of PST to PV provides insight into the
      distribution of sound pressure within the cochlear scalae.

PMID- 23556592
TI  - Input/output functions of different-latency components of transient-evoked and
      stimulus-frequency otoacoustic emissions.
AB  - The input/output functions of the different-latency components of human transient
      evoked and stimulus-frequency otoacoustic emissions are analyzed, with the goal
      of relating them to the underlying nonlinear dynamical properties of the basilar
      membrane response. Several cochlear models predict a cubic nonlinearity that
      would yield a correspondent compressive response. The otoacoustic response comes
      from different generation mechanisms, each characterized by a particular relation
      between local basilar membrane displacement and otoacoustic level. For the same
      mechanism (e.g., reflection from cochlear roughness), different generation places
      would imply differently compressive regimes of the local basilar membrane
      dynamics. Therefore, this kind of study requires disentangling these
      contributions, using suitable data acquisition and time-frequency analysis
      techniques. Fortunately, different generation mechanisms/places also imply
      different phase-gradient delays, knowledge of which can be used to perform this
      task. In this study, the different-latency otoacoustic components systematically
      show differently compressive response, consistent with two simple hypotheses: (1)
      all emissions come from the reflection mechanism and (2) the basilar membrane
      response is strongly compressive in the resonance region and closer to linear in
      more basal regions. It is not clear if such a compressive behavior also extends
      to arbitrarily low stimulus levels.

PMID- 23556591
TI  - Basilar-membrane interference patterns from multiple internal reflection of
      cochlear traveling waves.
AB  - At low stimulus levels, basilar-membrane (BM) mechanical transfer functions in
      sensitive cochleae manifest a quasiperiodic rippling pattern in both amplitude
      and phase. Analysis of the responses of active cochlear models suggests that the
      rippling is a mechanical interference pattern created by multiple internal
      reflection within the cochlea. In models, the interference arises when reverse
      traveling waves responsible for stimulus-frequency otoacoustic emissions (SFOAEs)
      reflect off the stapes on their way to the ear canal, launching a secondary
      forward-traveling wave that combines with the primary wave produced by the
      stimulus. Frequency-dependent phase differences between the two waves then create
      the rippling pattern measurable on the BM. Measurements of BM ripples and SFOAEs
      in individual chinchilla ears demonstrate that the ripples are strongly
      correlated with the acoustic interference pattern measured in ear-canal pressure,
      consistent with a common origin involving the generation of SFOAEs. In BM
      responses to clicks, the ripples appear as temporal fine structure in the
      response envelope (multiple lobes, waxing and waning). Analysis of the ripple
      spacing and response phase gradients provides a test for the role of fast- and
      slow-wave modes of reverse energy propagation within the cochlea. The data
      indicate that SFOAE delays are consistent with reverse slow-wave propagation but
      much too long to be explained by fast waves.

PMID- 23556593
TI  - Speech intelligibility among modulated and spatially distributed noise sources.
AB  - At a cocktail party, listeners are faced with multiple, spatially distributed
      interfering voices. The dominant interfering voice may change from moment to
      moment and, consequently, change in spatial location. The ability of the binaural
      system to deal with such a dynamic scene has not been systematically analyzed.
      Spatial release from masking (SRM) was measured in simple spatial scenes,
      simulated over headphones with a frontal speech source. For a single noise at 105
      degrees , SRM was reduced if that noise modulated (10 Hz square wave, 50% duty
      cycle, 20 dB modulation depth), but, for two noises in symmetrical locations, SRM
      increased if the noises were modulated in alternation, suggesting that the
      binaural system can "switch" between exploiting different spatial configurations.
      Experiment 2 assessed the contributions of interaural time and level differences
      as a function of modulation rate (1-20 Hz). Scenes were created using the
      original head-related impulse responses and ones that had been manipulated to
      isolate each cue. SRM decreased steeply with modulation rate. The combined
      effects of interaural time and level differences were consistent with additive
      contributions. The results indicate that binaural sluggishness limits the
      contribution of binaural switching to speech understanding at a cocktail party.

PMID- 23556594
TI  - Binaural notched-noise masking and auditory-filter shape.
AB  - Thresholds for sinusoids interaurally in phase (S0) and antiphase (Spi) were
      measured in the presence of a diotic notched-noise masker (N0) as a function of
      notch width. The signal frequency was 250, 500, 1000, or 2000 Hz. For all signal
      frequencies, the difference between N0S0 and N0Spi thresholds (binaural masking
      level difference, BMLD) decreased continuously as the notch width increased.
      Model simulations showed that this result cannot be accounted for by a model that
      only processes the output of the auditory filter centered at the signal
      frequency, even if the nonlinear behavior of the monaural frequency selectivity
      or interaural differences in the filter shape are considered. The data were
      predicted well if a detrimental across-channel process was included, either by an
      addition of portions of the output of adjacent filters to the output of the on
      frequency filter or by a notch-width dependent adverse shift in interaural phase
      in the binaural stage. The strength of this detrimental across-channel process
      tends to decrease with increasing signal frequencies.

PMID- 23556595
TI  - Effect of mismatched place-of-stimulation on the salience of binaural cues in
      conditions that simulate bilateral cochlear-implant listening.
AB  - Although bilateral cochlear implantation has the potential to improve sound
      localization and speech understanding in noise, obstacles exist in presenting
      maximally useful binaural information to bilateral cochlear-implant (CI) users.
      One obstacle is that electrode arrays may differ in cochlear position by several
      millimeters, thereby stimulating different neural populations. Effects of
      interaural frequency mismatch on binaural processing were studied in normal
      hearing (NH) listeners using band-limited pulse trains, thereby avoiding
      confounding factors that may occur in CI users. In experiment 1, binaural image
      fusion was measured to capture perceptual number, location, and compactness.
      Subjects heard a single, compact image on 73% of the trials. In experiment 2,
      intracranial image location was measured for different interaural time
      differences (ITDs) and interaural level differences (ILDs). For larger mismatch,
      locations perceptually shifted towards the ear with the higher carrier frequency.
      In experiment 3, ITD and ILD just-noticeable differences (JNDs) were measured.
      JNDs increased with decreasing bandwidth and increasing mismatch, but were always
      measurable up to 3 mm of mismatch. If binaural-hearing mechanisms are similar
      between NH and CI subjects, these results may explain reduced sensitivity of ITDs
      and ILDs in CI users. Large mismatches may lead to distorted spatial maps and
      reduced binaural image fusion.

PMID- 23556596
TI  - Factors affecting the use of envelope interaural time differences in
      reverberation.
AB  - At high frequencies, interaural time differences (ITDs) are conveyed by the sound
      envelope. Sensitivity to envelope ITDs depends crucially on the envelope shape.
      Reverberation degrades the envelope shape, reducing the modulation depth of the
      envelope and the slope of its flanks. Reverberation also reduces the envelope
      interaural coherence (i.e., the similarity of the envelopes at two ears). The
      current study investigates the extent to which these changes affect sensitivity
      to envelope ITDs. The first experiment measured ITD discrimination thresholds at
      low and high frequencies in a simulated room. The stimulus was either a low
      frequency narrowband noise or the same noise transposed to a higher frequency.
      The results suggest that the effect of reverberation on ITD thresholds was
      multiplicative. Given that the threshold without reverberation was larger for the
      transposed than for the low-frequency stimulus, this meant that, in absolute
      terms, the thresholds for the transposed stimulus showed a much greater increase
      due to reverberation than those for the low-frequency stimulus. Three further
      experiments indicated that the effect of reverberation on the envelope ITD
      thresholds was due to the combined effect of the reduction in the envelope
      modulation depth and slopes, as well as the decrease in the envelope interaural
      coherence.

PMID- 23556597
TI  - Localizing the sources of two independent noises: role of time varying amplitude
      differences.
AB  - Listeners localized the free-field sources of either one or two simultaneous and
      independently generated noise bursts. Listeners' localization performance was
      better when localizing one rather than two sound sources. With two sound sources,
      localization performance was better when the listener was provided prior
      information about the location of one of them. Listeners also localized two
      simultaneous noise bursts that had sinusoidal amplitude modulation (AM) applied,
      in which the modulation envelope was in-phase across the two source locations or
      was 180 degrees  out-of-phase. The AM was employed to investigate a hypothesis as
      to what process listeners might use to localize multiple sound sources. The
      results supported the hypothesis that localization of two sound sources might be
      based on temporal-spectral regions of the combined waveform in which the sound
      from one source was more intense than that from the other source. The interaural
      information extracted from such temporal-spectral regions might provide reliable
      estimates of the sound source location that produced the more intense sound in
      that temporal-spectral region.

PMID- 23556598
TI  - Sensitivity of bilateral cochlear implant users to fine-structure and envelope
      interaural time differences.
AB  - Bilateral cochlear implant users have poor sensitivity to interaural time
      differences (ITDs) of high-rate pulse trains, which precludes use of these
      stimuli to convey fine-structure ITD cues. However, previous reports of single
      neuron recordings in cats demonstrated good ITD sensitivity to 1000 pulses-per
      second (pps) pulses when the pulses were sinusoidally amplitude modulated. The
      ability of modulation to restore ITD sensitivity to high-rate pulses in humans
      was tested by measuring ITD thresholds for three conditions: ITD encoded in the
      modulated carrier pulses alone, in the envelope alone, and in the whole waveform.
      Five of six subjects were not sensitive to ITD in the 1000-pps carrier, even with
      modulation. One subject's 1000-pps carrier ITD sensitivity did significantly
      improve due to modulation. Sensitivity to ITD encoded in the envelope was also
      measured as a function of modulation frequency, including at frequencies from 4
      to 16 Hz where much of the speech envelope's energy and information resides.
      Sensitivity was best at the modulation frequency of 100 Hz and degraded rapidly
      outside of a narrow range. These results provide little evidence to support
      encoding ITD in the carrier of current bilateral processors, and suggest envelope
      ITD sensitivity is poor for an important segment of the speech modulation
      spectrum.

PMID- 23556599
TI  - Effects of dynamic range compression on spatial selective auditory attention in
      normal-hearing listeners.
AB  - Many hearing aids introduce compressive gain to accommodate the reduced dynamic
      range that often accompanies hearing loss. However, natural sounds produce
      complicated temporal dynamics in hearing aid compression, as gain is driven by
      whichever source dominates at a given moment. Moreover, independent compression
      at the two ears can introduce fluctuations in interaural level differences (ILDs)
      important for spatial perception. While independent compression can interfere
      with spatial perception of sound, it does not always interfere with localization
      accuracy or speech identification. Here, normal-hearing listeners reported a
      target message played simultaneously with two spatially separated masker
      messages. We measured the amount of spatial separation required between the
      target and maskers for subjects to perform at threshold in this task. Fast,
      syllabic compression that was independent at the two ears increased the required
      spatial separation, but linking the compressors to provide identical gain to both
      ears (preserving ILDs) restored much of the deficit caused by fast, independent
      compression. Effects were less clear for slower compression. Percent-correct
      performance was lower with independent compression, but only for small spatial
      separations. These results may help explain differences in previous reports of
      the effect of compression on spatial perception of sound.

PMID- 23556600
TI  - Voicing produced by a constant velocity lung source.
AB  - An investigation is made of the influence of subglottal boundary conditions on
      the prediction of voiced sounds. It is generally assumed in mathematical models
      of voicing that vibrations of the vocal folds are maintained by a constant
      subglottal mean pressure pI, whereas voicing is actually initiated by contraction
      of the chest cavity until the subglottal pressure becomes large enough to
      separate the vocal folds. The problem is reformulated to determine voicing
      characteristics in terms of a prescribed volumetric flow rate Qo of air from the
      lungs-the evolution of the resulting time-dependent subglottal mean pressure
      p[overline]-(t) is then governed by glottal mechanics, the aeroacoustics of the
      vocal tract, and the influence of continued contraction of the lungs. The new
      problem is analyzed in detail for an idealized mechanical vocal system that
      permits precise specification of all boundary conditions. Predictions of the
      glottal volume velocity pulse shape are found to be in good general agreement
      with the traditional constant-pI theory when pI is set equal to the time averaged
      value of p[overline]-(t). But, in all cases examined the constant-pI
      approximation yields values of the mean flow rates Qo and sound pressure levels
      that are smaller by as much as 10%.

PMID- 23556601
TI  - The time course of perception of coarticulation.
AB  - The perception of coarticulated speech as it unfolds over time was investigated
      by monitoring eye movements of participants as they listened to words with oral
      vowels or with late or early onset of anticipatory vowel nasalization. When
      listeners heard [CVNC] and had visual choices of images of CVNC (e.g., send) and
      CVC (said) words, they fixated more quickly and more often on the CVNC image when
      onset of nasalization began early in the vowel compared to when the
      coarticulatory information occurred later. Moreover, when a standard eye movement
      programming delay is factored in, fixations on the CVNC image began to occur
      before listeners heard the nasal consonant. Listeners' attention to
      coarticulatory cues for velum lowering was selective in two respects: (a)
      listeners assigned greater perceptual weight to coarticulatory information in
      phonetic contexts in which [V] but not N is an especially robust property, and
      (b) individual listeners differed in their perceptual weights. Overall, the time
      course of perception of velum lowering in American English indicates that the
      dynamics of perception parallel the dynamics of the gestural information encoded
      in the acoustic signal. In real-time processing, listeners closely track
      unfolding coarticulatory information in ways that speed lexical activation.

PMID- 23556602
TI  - Perceptual adaptation to gender and expressive properties in speech: the role of
      fundamental frequency.
AB  - Recent studies have demonstrated perceptual adaptation to nonlinguistic
      properties of speech involving voice gender and emotional expression. The present
      study extends this work by examining the contribution of fundamental frequency
      (F0) to these effects. Voice recordings of vowel-consonant-vowel (VCV) syllables
      from six talkers were processed using the STRAIGHT vocoder and an auditory
      morphing technique to synthesize gender (experiment 1) and expressive (experiment
      2) speech sound continua ranging from one category endpoint to the other (female
      to male; angry to happy). Continuum endpoints served as adaptors for F0 present
      and F0 removed conditions. F0 removed stimuli were created by replacing the
      periodic excitation source with broadband noise. Confirming previous findings,
      aftereffects were found in the F0 present condition, resulting in a decreased
      likelihood to identify test stimuli as belonging to the adaptor category. No
      aftereffects appeared when F0 was removed, highlighting the importance of F0 in
      adaptation. However, in an identification test listeners were still able to
      categorize F0 removed stimuli at better-than-chance levels, indicating that
      residual cues for gender and emotion were available even when F0 was not present.

PMID- 23556603
TI  - Detection of shouted speech in noise: human and machine.
AB  - High vocal effort has characteristic acoustic effects on speech. This study
      focuses on the utilization of this information by human listeners and a machine
      based detection system in the task of detecting shouted speech in the presence of
      noise. Both female and male speakers read Finnish sentences using normal and
      shouted voice in controlled conditions, with the sound pressure level recorded.
      The speech material was artificially corrupted by noise and supplemented with
      pure noise. The human performance level was statistically evaluated by a
      listening test, where the subjects labeled noisy samples according to whether
      shouting was heard or not. A Bayesian detection system was constructed and
      statistically evaluated. Its performance was compared against that of human
      listeners, substituting different spectrum analysis methods in the feature
      extraction stage. Using features capable of taking into account the spectral fine
      structure (i.e., the fundamental frequency and its harmonics), the machine
      reached the detection level of humans even in the noisiest conditions. In the
      listening test, male listeners detected shouted speech significantly better than
      female listeners, especially with speakers making a smaller vocal effort increase
      for shouting.

PMID- 23556604
TI  - Recognition of speech in noise after application of time-frequency masks:
      dependence on frequency and threshold parameters.
AB  - Binary time-frequency (TF) masks can be applied to separate speech from noise.
      Previous studies have shown that with appropriate parameters, ideal TF masks can
      extract highly intelligible speech even at very low speech-to-noise ratios
      (SNRs). Two psychophysical experiments provided additional information about the
      dependence of intelligibility on the frequency resolution and threshold criteria
      that define the ideal TF mask. Listeners identified AzBio Sentences in noise,
      before and after application of TF masks. Masks generated with 8 or 16 frequency
      bands per octave supported nearly-perfect identification. Word recognition
      accuracy was slightly lower and more variable with 4 bands per octave. When TF
      masks were generated with a local threshold criterion of 0 dB SNR, the mean
      speech reception threshold was -9.5 dB SNR, compared to -5.7 dB for unprocessed
      sentences in noise. Speech reception thresholds decreased by about 1 dB per dB of
      additional decrease in the local threshold criterion. Information reported here
      about the dependence of speech intelligibility on frequency and level parameters
      has relevance for the development of non-ideal TF masks for clinical applications
      such as speech processing for hearing aids.

PMID- 23556605
TI  - Focusing the lens of language experience: perception of Ma'di stops by Greek and
      English bilinguals and monolinguals.
AB  - Monolingual listeners are constrained by native language experience when
      categorizing and discriminating unfamiliar non-native contrasts. Are early
      bilinguals constrained in the same way by their two languages, or do they possess
      an advantage? Greek-English bilinguals in either Greek or English language mode
      were compared to monolinguals on categorization and discrimination of Ma'di stop
      voicing distinctions that are non-native to both languages. As predicted, English
      monolinguals categorized Ma'di prevoiced plosive and implosive stops and the
      coronal voiceless stop as English voiced stops. The Greek monolinguals
      categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the
      prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops.
      Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the
      non-native voiced-voiceless contrasts very well, whereas the English monolinguals
      did poorly. Bilinguals were given all oral and written instructions either in
      English or in Greek (language mode manipulation). Each language mode subgroup
      categorized Ma'di stop-voicing comparably to the corresponding monolingual group.
      However, the bilinguals' discrimination was unaffected by language mode: both
      subgroups performed intermediate to the monolinguals for the prevoiced-voiceless
      contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native
      contrasts, but are nonetheless uniquely configured language users, differing from
      either monolingual group.

PMID- 23556606
TI  - A beamformer post-filter for cochlear implant noise reduction.
AB  - Cochlear implant users have limited ability to understand speech in noisy
      conditions. Signal processing methods to address this issue that use multiple
      microphones typically use beamforming to perform noise reduction. However, the
      effectiveness of the beamformer is diminished as the number of interfering noises
      increases and the acoustic environment becomes more diffuse. A multi-microphone
      noise reduction algorithm that aims to address this issue is presented in this
      study. The algorithm uses spatial filtering to estimate the signal-to-noise ratio
      (SNR) and attenuates time-frequency elements that have poor SNR. The algorithm
      was evaluated by measuring intelligibility of speech embedded in 4-talker babble
      where the interfering talkers were spatially separated and changed location
      during the test. Twelve cochlear implant users took part in the evaluation, which
      demonstrated a significant mean improvement of 4.6 dB (standard error 0.4, P <
      0.001) in speech reception threshold compared to an adaptive beamformer. The
      results suggest that a substantial improvement in performance can be gained for
      cochlear implant users in noisy environments where the noise is spatially
      separated from the target speech.

PMID- 23556607
TI  - Contribution of temporal fine structure information and fundamental frequency
      separation to intelligibility in a competing-speaker paradigm.
AB  - The speech reception threshold (SRT) for identifying a target speaker in a
      background speaker was measured as a function of the difference (F0sep) in
      fundamental frequency (F0) between the two speakers. The amount of original
      temporal fine structure (TFS) information in the mixed signals was manipulated by
      tone vocoding channels above a certain cutoff channel (CO). When the natural
      variations in F0 of both speakers were preserved, the SRT did not decrease with
      increasing F0sep, indicating that short-term differences in F0 can allow
      perceptual segregation of two speakers even when their F0s cross. When F0
      variations were removed from both speakers, increasing F0sep led to decreased
      (better) SRTs. The decrease was greater for unprocessed signals than for fully
      tone-vocoded signals. However, the decrease was similar for unprocessed signals
      and for signals with original TFS below 1600 Hz, suggesting that most of the
      benefit from increasing F0 difference depends on the use of TFS information at
      lower frequencies. Adding original TFS information to channels centered above
      1600 Hz produced roughly the same decrease in SRT as adding original TFS
      information to channels centered below 1600 Hz, suggesting a benefit from
      original TFS information apart from that related to differences in F0.

PMID- 23556609
TI  - A model of harp plucking.
AB  - In this paper, a model of the harp plucking is developed. It is split into two
      successive time phases, the sticking and the slipping phases, and uses a
      mechanical description of the human finger's behavior. The parameters of the
      model are identified through measurements of the finger/string displacements
      during the interaction. The validity of the model is verified using a
      configurable and repeatable robotic finger, enhanced with a silicone layer. A
      parametric study is performed to investigate the influence of the model's
      parameters on the free oscillations of the string. As a result, a direct
      implementation of the model produces an accurate simulation of a string response
      to a given finger motion, as compared to experimental data. The set of parameters
      that govern the plucking action is divided into two groups: Parameters controlled
      by the harpist and parameters intrinsic to the plucking. The former group and to
      a lesser extent the latter highly influence the initial conditions of the string
      vibrations. The simulations of the string's free oscillations highlight the large
      impact the model parameters have on the sound produced and therefore allows the
      understanding of how different players on the same instrument can produce a
      specific/personal sound quality.

PMID- 23556608
TI  - Listening to speech in a background of other talkers: effects of talker number
      and noise vocoding.
AB  - Some of the most common interfering background sounds a listener experiences are
      the sounds of other talkers. In Experiment 1, recognition for natural Institute
      of Electrical and Electronics Engineers (IEEE) sentences was measured in normal
      hearing adults at two fixed signal-to-noise ratios (SNRs) in 16 backgrounds with
      the same long-term spectrum: unprocessed speech babble (1, 2, 4, 8, and 16
      talkers), noise-vocoded versions of the babbles (12 channels), noise modulated
      with the wide-band envelope of the speech babbles, and unmodulated noise. All
      talkers were adult males. For a given number of talkers, natural speech was
      always the most effective masker. The greatest changes in performance occurred as
      the number of talkers in the maskers increased from 1 to 2 or 4, with small
      changes thereafter. In Experiment 2, the same targets and maskers (1, 2, and 16
      talkers) were used to measure speech reception thresholds (SRTs) adaptively.
      Periodicity in the target was also manipulated by noise-vocoding, which led to
      considerably higher SRTs. The greatest masking effect always occurred for the
      masker type most similar to the target, while the effects of the number of
      talkers were generally small. Implications are drawn with reference to glimpsing,
      informational vs energetic masking, overall SNR, and aspects of periodicity.

PMID- 23556610
TI  - Dynamical properties of piano soundboards.
AB  - In pianos, the transfer of energy from strings to soundboard and the radiation of
      sound are highly dependent on the dynamical properties of the soundboard. In this
      paper, a numerical study is conducted for various rib configurations, showing
      that even slight irregularities in rib spacing can induce a strong localization
      of the soundboard velocity pattern. The effective vibrating area can be further
      reduced due to the spatial filtering effect of the bridge. Numerical predictions
      of modal shapes and operating deflection shapes are confirmed by series of
      measurements made on upright piano soundboards. Simulations of radiated pressure
      based on measured and calculated soundboard velocity fields show that
      localization tends to broaden the cone of directivity and to reduce the number of
      lobes.

PMID- 23556611
TI  - Experimental investigation of the piano hammer-string interaction.
AB  - Experimental techniques for investigating the piano hammer-string interaction are
      described. It is argued that the accuracy, consistency, and scope of conclusions
      of previous studies can be compromised by limitations of the conventional methods
      relating to key inputs; physical distortion; numerical distortion, particularly
      when differentiation or integration of measured signals is used to derive primary
      response variables; contact identification; and synchronization issues. These
      problems are discussed, and experimental methods that have been devised to avoid
      them are described and illustrated by detailed results from a study of the hammer
      string interaction in a vertical piano. High resolution displacements are
      obtained directly by non-contact high-speed imaging and quantitative motion
      tracking. The attention focused on achieving very accurate and consistent
      temporal and spatial alignment, including the objective procedure used for
      contact identification, allows meaningful comparisons of responses from separate
      tests. String motion at the strike point and on each side of it, as well as
      hammer motion, is obtained for eight dynamic levels from 1.06 to 2.98 m/s impact
      velocity. Detailed observations of the force-compression behavior of the hammer
      interacting with real strings are presented. The direct effects of hammer shank
      deflection and agraffe string pulses on the interaction are also highlighted.

PMID- 23556612
TI  - Whistle characteristics of free-ranging Indo-Pacific humpback dolphins (Sousa
      chinensis) in Sanniang Bay, China.
AB  - Broadband recording systems were adapted to characterize the whistle
      characteristics of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis)
      in Sanniang Bay, China. A total of 4630 whistles were recorded, of which 2651
      with legible contours and relatively good signal-to-noise ratios were selected
      for statistical analysis. Of the six tonal types (i.e., flat, down, rise, convex,
      U-shaped, and sine), flat (N = 1426; 39.45%) was the most predominant, followed
      by down (N = 754; 23.35%) and rise (N = 489; 12.34%). The whistles showed a short
      duration (mean +/- SD: 370.19 +/- 285.61 ms; range: 29-2923 ms), a broad
      frequency range (fundamental contour ranged from 0.52 to 33 kHz), and two
      harmonics (mean +/- SD: 1.90 +/- 2.74, with the maximum frequency of harmonics
      beyond 96 kHz). Whistles without gaps and stairs accounted for 76.7% and 86.4%,
      respectively. No significant interspecies differences in frequency parameters
      were observed compared with S. teuszii, which is inconsistent with morphological
      taxonomies but confirms phylogenetic results, thus suggesting a close relation
      between Chinese S. chinensis and Atlantic S. teuszii. Significant intra- and
      interspecific differences in the genus Sousa were also observed, indicating that
      animal vocalization may not be limited by genetically determined traits but could
      also be a function of local habitat adaptation.

PMID- 23556613
TI  - Estimation of fast and slow wave properties in cancellous bone using Prony's
      method and curve fitting.
AB  - The presence of two longitudinal waves in poroelastic media is predicted by
      Biot's theory and has been confirmed experimentally in through-transmission
      measurements in cancellous bone. Estimation of attenuation coefficients and
      velocities of the two waves is challenging when the two waves overlap in time.
      The modified least squares Prony's (MLSP) method in conjuction with curve-fitting
      (MLSP + CF) is tested using simulations based on published values for fast and
      slow wave attenuation coefficients and velocities in cancellous bone from several
      studies in bovine femur, human femur, and human calcaneus. The search algorithm
      is accelerated by exploiting correlations among search parameters. The
      performance of the algorithm is evaluated as a function of signal-to-noise ratio
      (SNR). For a typical experimental SNR (40 dB), the root-mean-square errors
      (RMSEs) for one example (human femur) with fast and slow waves separated by
      approximately half of a pulse duration were 1 m/s (slow wave velocity), 4 m/s
      (fast wave velocity), 0.4 dB/cm MHz (slow wave attenuation slope), and 1.7 dB/cm
      MHz (fast wave attenuation slope). The MLSP + CF method is fast (requiring less
      than 2 s at SNR = 40 dB on a consumer-grade notebook computer) and is flexible
      with respect to the functional form of the parametric model for the transmission
      coefficient. The MLSP + CF method provides sufficient accuracy and precision for
      many applications such that experimental error is a greater limiting factor than
      estimation error.

PMID- 23556683
TI  - An optoacoustic point source for acoustic scale model measurements.
AB  - A massless acoustic source is proposed for scale model work. This source is
      generated by focusing a pulsed laser beam to rapidly heat the air at the focal
      point. This produces an expanding small plasma ball which generates a sonic
      impulse that may be used as an acoustic point source. Repeatability, frequency
      response, and directivity of the source were measured to show that it can serve
      as a massless point source. The impulse response of a rectangular space was
      determined using this type of source. A good match was found between the
      predicted and the measured impulse responses of the space.

PMID- 23556684
TI  - Using Fisher information to quantify uncertainty in environmental parameters
      estimated from correlated ambient noise.
AB  - Efforts to characterize environmental parameters from ambient noise must contend
      with uncertainty introduced by stochastic fluctuations of the noise itself. This
      Letter calculates the Fisher information and Cramer-Rao bound of an unbiased
      correlated ambient noise parameter estimate. As an illustration, lower bounds on
      the error covariance of medium speed and attenuation parameters are obtained for
      a two-dimensional isotropic ambient noise scenario. The results demonstrate that
      an optimal sensor separation exists for obtaining the minimum error and the
      predictions are validated using simulated parameter inversions. The influences of
      record length, bandwidth, signal-to-noise, and spatial resolution are discussed.

PMID- 23556685
TI  - Detection of early reflections using multifractals.
AB  - Early reflections are not always strong and sparse enough on the timeline to be
      easily identified when reviewing the impulse response diagram. This paper
      presents a method for the detection of early reflection in the room impulse
      response using multifractals. The proposed method uses the distribution of
      Holder's exponent calculated for the acoustic impulse response for early
      reflection detection. The obtained results confirm the assumption that impulse
      response signals exhibit self-similarity, and that fractal theory can be used for
      the detection of early reflections.

PMID- 23556686
TI  - Information transfer in auditoria and room-acoustical quality.
AB  - It is hypothesized that room-acoustical quality correlates with the information
      transfer rate. Auditoria are considered as multiple-input multiple-output
      communication channels and a theory of information-transfer is outlined that
      accounts for time-variant multipath, spatial hearing, and distributed directional
      sources. Source diversity and spatial hearing are shown to be the mechanisms
      through which multipath increases the information-transfer rate by overcoming
      finite spatial resolution. In addition to predictions that are confirmed by
      recent and historical findings, the theory provides explanations for the
      influence of factors such as musical repertoire and ensemble size on subjective
      preference and the influence of multisource, multichannel auralization on
      perceived realism.

PMID- 23556687
TI  - Anticipatory lip gestures: a validation of the Movement Expansion Model in
      congenitally blind speakers.
AB  - In this paper, anticipatory co-articulation of the lip protrusion and
      constriction gestures is investigated in speakers with visual deprivation. Audio
      visual recordings of 11 congenitally blind French speakers producing [V-roundC
      roundV+round] sequences were measured with a lip shape tracking system. Lip
      protrusion and constriction values and their relative timings were analyzed.
      Results show that despite the reduced magnitude of lip protrusion and
      constriction area in blind speakers, the timing of the anticipatory gestures can
      be appropriately modeled by the Movement Expansion Model [from Abry and
      Lallouache (1995a). Bul. de la Comm. Parlee 3, 85-99; (1995b). Proceedings of
      ICPHS, pp. 152-155; Noiray et al. (2011). J. Acoust. Soc. Am. 129, 340-349],
      which predicts lawful anticipatory behavior expanding linearly as the
      intervocalic consonant interval increases.

PMID- 23556688
TI  - Hysteretic nonlinearity analysis in damaged composite plates using guided waves.
AB  - Sensitivity of nonlinear acoustic methods to the presence and the evolution of
      micro-damage has been proven in various studies on a wide range of materials. In
      this contribution, a guided wave approach is proposed to characterize polymer
      based composite plates taken at intact as well as damaged states. The changes in
      the nonlinear hysteretic parameters are observed by changing the order of the
      excited flexural resonances. The analysis is based on the evolution of the
      velocity frequency dispersion of the generated guided waves, where flexural modes
      are considered separately and together as a function of the dynamic strain.

PMID- 23556689
TI  - Spectral probability density as a tool for ambient noise analysis.
AB  - This paper presents the empirical probability density of the power spectral
      density as a tool to assess the field performance of passive acoustic monitoring
      systems and the statistical distribution of underwater noise levels across the
      frequency spectrum. Using example datasets, it is shown that this method can
      reveal limitations such as persistent tonal components and insufficient dynamic
      range, which may be undetected by conventional techniques. The method is then
      combined with spectral averages and percentiles, which illustrates how the
      underlying noise level distributions influence these metrics. This combined
      approach is proposed as a standard, integrative presentation of ambient noise
      spectra.

PMID- 23556690
TI  - Computationally efficient parabolic equation solutions to seismo-acoustic
      problems involving thin or low-shear elastic layers.
AB  - Shallow-water environments typically include sediments containing thin or low
      shear layers. Numerical treatments of these types of layers require finer depth
      grid spacing than is needed elsewhere in the domain. Thin layers require finer
      grids to fully sample effects due to elasticity within the layer. As shear wave
      speeds approach zero, the governing system becomes singular and fine-grid spacing
      becomes necessary to obtain converged solutions. In this paper, a seismo-acoustic
      parabolic equation solution is derived utilizing modified difference formulas
      using Galerkin's method to allow for variable-grid spacing in depth. Propagation
      results are shown for environments containing thin layers and low-shear layers.

PMID- 23556691
TI  - Bayesian tracking of multiple acoustic sources in an uncertain ocean environment.
AB  - This letter develops a Bayesian approach to matched-field tracking of multiple
      acoustic sources in a poorly-known environment. Markov-chain Monte Carlo methods
      explicitly sample the posterior probability density over source locations and
      environmental parameters, while analytic maximum-likelihood solutions for complex
      source strengths and noise variance in terms of the explicit parameters allow
      these parameters to be sampled efficiently. This produces a time-ordered sequence
      of joint marginal probability distributions over source range and depth, from
      which optimal track estimates and uncertainties are extracted. Synthetic examples
      consider tracking a submerged source in the presence of a louder shallow
      interferer in an unknown environment.

PMID- 23556692
TI  - Temporally pre-presented lipreading cues release speech from informational
      masking.
AB  - Listeners can use temporally pre-presented content cues and concurrently
      presented lipreading cues to improve speech recognition under masking conditions.
      This study investigated whether temporally pre-presented lipreading cues also
      unmask speech. In a test trial, before the target sentence was co-presented with
      the masker, either target-matched (priming) lipreading video or static face
      (priming-control) video was presented in quiet. Participants' target-recognition
      performance was improved by a shift from the priming-control condition to the
      priming condition when the masker was speech but not noise. This release from
      informational masking suggests a combined effect of working memory and cross
      modal integration on selective attention to target speech.

PMID- 23556693
TI  - Inner speech captures the perception of external speech.
AB  - Talking silently to ourselves occupies much of our mental lives, yet the
      mechanisms underlying this experience remain unclear. The following experiments
      provide behavioral evidence that the auditory content of inner speech is provided
      by corollary discharge. Corollary discharge is the motor system's prediction of
      the sensory consequences of its actions. This prediction can bias perception of
      other sensations, pushing percepts to match with prediction. The two experiments
      below show this bias induced by inner speech, demonstrating that inner speech
      causes external sounds to be heard as similar to the imagined speech, and that
      this bias operates on subphonemic content.

PMID- 23556694
TI  - Compensating for identification errors in memory recall tasks.
AB  - A mathematical model for approximating the contributions of identification and
      recall errors on the ability to repeat a list of N items is developed. In memory
      recall tasks where the items are independent and unrelated to each other, the
      probability of correctly repeating a list of items can be approximated as the
      product of the probability of correctly recalling all the items and the
      probability of correctly identifying an isolated item raised to the power of N.
      This relationship suggests that unaccounted for reductions in identification
      performance can severely affect estimates of memory.

PMID- 23556695
TI  - Covert underwater acoustic communication using dolphin sounds.
AB  - In November 2012, an experiment demonstrating biological mimicry method for
      covert underwater acoustic communication (UAC) was conducted at Lianhua Lake in
      Heilongjiang China. Dolphin whistles were used for synchronization while dolphin
      clicks were used as information carrier. The time interval between dolphin clicks
      conveys the information bits. Channel estimates were obtained with matching
      pursuit (MP) algorithm, which is useful for sparse channel estimation. Adaptive
      RAKE Equalization was employed at the receiver. Bit error rates were less than
      10(-4) with 37 bits per second data rate in the lake trial.

PMID- 23556696
TI  - Minimum classification error-based weighted support vector machine kernels for
      speaker verification.
AB  - Support vector machines (SVMs) have been proved to be an effective approach to
      speaker verification. An appropriate selection of the kernel function is a key
      issue in SVM-based classification. In this letter, a new SVM-based speaker
      verification method utilizing weighted kernels in the Gaussian mixture model
      supervector space is proposed. The weighted kernels are derived by using the
      discriminative training approach, which minimizes speaker verification errors.
      Experiments performed on the NIST 2008 speaker recognition evaluation task showed
      that the proposed approach provides substantially improved performance over the
      baseline kernel-based method.

PMID- 23556697
TI  - Relation between loudness in categorical units and loudness in phons and sones.
AB  - Data are presented on the relation between loudness measured in categorical units
      (CUs) using a standardized loudness scaling method (ISO 16832, 2006) and loudness
      expressed as the classical standardized measures phon and sone. Based on loudness
      scaling of narrowband noise signals by 31 normal-hearing subjects, sound pressure
      levels eliciting the same categorical loudness were derived for various center
      frequencies. The results were comparable to the standardized equal-loudness level
      contours. A comparison between the loudness function in CUs at 1000 Hz and the
      standardized loudness function in sones indicates a cubic relation between the
      two loudness measures.

PMID- 23556698
TI  - Depth-based signal separation with vertical line arrays in the deep ocean.
AB  - Deep vertical line arrays can exploit the reliable acoustic path (RAP), which
      provides low transmission loss (TL) for targets at moderate ranges, and increased
      TL for distant interferers. However, nearby surface interference also has
      favorable RAP propagation and cannot be separated from a submerged target without
      horizontal aperture. In this work, a physics-based Fourier transform variant is
      introduced, which achieves depth-based signal separation by exploiting the
      spatial structure resulting from the coherent addition of the direct and surface
      reflected propagation paths present for submerged sources. Simulation results
      demonstrate depth-based signal separation without requiring knowledge of the
      ocean environment.

PMID- 23556699
TI  - Underwater noise of small personal watercraft (jet skis).
AB  - Personal watercraft (water scooters, jet skis) were recorded under water in
      Bramble Bay, Queensland, Australia. Underwater noise emissions consisted of
      broadband energy between 100 Hz and 10 kHz due to the vibrating bubble cloud
      generated by the jet stream, overlain with frequency-modulated tonals
      corresponding to impeller blade rates and harmonics. Broadband monopole source
      levels were 149, 137, and 122 dB re 1 MUPa @ 1 m (5th, 50th, and 95th
      percentiles). Even though these are lower than those of small propeller-driven
      boats, it is not necessarily the broadband source level that correlates with the
      bioacoustic impact on marine fauna.

PMID- 23556700
TI  - Distortion product otoacoustic emissions upon ear canal pressurization.
AB  - The purpose of this study was to quantify the change in distortion product
      otoacoustic emission (DPOAE) level upon ear canal pressurization. DPOAEs were
      measured on 12 normal-hearing human subjects for ear canal static pressures
      between -200 and +200 daPa in (50 +/- 5) daPa steps. A clear dependence of DPOAE
      levels on the pressure was observed, with levels being highest at the maximum
      compliance of the middle ear, and decreasing on average by 2.3 dB per 50 daPa for
      lower and higher pressures. Ear canal pressurization can serve as a tool for
      improving the detectability of DPOAEs in the case of middle-ear dysfunction.

PMID- 23556701
TI  - Communication: Growing room temperature ice with graphene.
AB  - Water becomes ordered in the form of hexagonal ice at room temperature under
      controlled humidity conditions upon confinement in the nanometer range between
      protective graphene sheets and crystalline (111) surfaces with hexagonal symmetry
      of the alkali earth fluoride BaF2. Interfacial water/substrate pseudoepitaxy
      turns out to be a critical parameter since ice is only formed when the lattice
      mismatch is small, an observation based on the absence of ice on (111) surfaces
      of isostructural CaF2.

PMID- 23556702
TI  - Communication: A new ab initio potential energy surface for HCl-H2O, diffusion
      Monte Carlo calculations of D0 and a delocalized zero-point wavefunction.
AB  - We report a global, full-dimensional, ab initio potential energy surface
      describing the HCl-H2O dimer. The potential is constructed from a permutationally
      invariant fit, using Morse-like variables, to over 44,000 CCSD(T)-F12b/aug-cc
      pVTZ energies. The surface describes the complex and dissociated monomers with a
      total RMS fitting error of 24 cm(-1). The normal modes of the minima, low-energy
      saddle point and separated monomers, the double minimum isomerization pathway and
      electronic dissociation energy are accurately described by the surface. Rigorous
      quantum mechanical diffusion Monte Carlo (DMC) calculations are performed to
      determine the zero-point energy and wavefunction of the complex and the separated
      fragments. The calculated zero-point energies together with a De value calculated
      from CCSD(T) with a complete basis set extrapolation gives a D0 value of 1348 +/-
      3 cm(-1), in good agreement with the recent experimentally reported value of 1334
      +/- 10 cm(-1) [B. E. Casterline, A. K. Mollner, L. C. Ch'ng, and H. Reisler, J.
      Phys. Chem. A 114, 9774 (2010)]. Examination of the DMC wavefunction allows for
      confident characterization of the zero-point geometry to be dominant at the C(2v)
      double-well saddle point and not the C(s) global minimum. Additional support for
      the delocalized zero-point geometry is given by numerical solutions to the 1D
      Schrodinger equation along the imaginary-frequency out-of-plane bending mode,
      where the zero-point energy is calculated to be 52 cm(-1) above the isomerization
      barrier. The D0 of the fully deuterated isotopologue is calculated to be 1476 +/-
      3 cm(-1), which we hope will stand as a benchmark for future experimental work.

PMID- 23556703
TI  - Analytical energy gradient used in variational Born-Oppenheimer calculations with
      all-electron explicitly correlated Gaussian functions for molecules containing
      one pi electron.
AB  - An algorithm for variational calculations of molecules with one pi electron
      performed with all-electron explicitly correlated gaussian (ECG) functions with
      floating centers is derived and implemented. The algorithm includes the analytic
      gradient of the Born-Oppenheimer electronic energy determined with respect to the
      ECG exponential parameters and the coordinates of the gaussian centers. The
      availability of the gradient greatly accelerates the variational energy
      minimization. The algorithm is tested in calculations of four electronic excited
      states, c(3)Pi(u), C(1)Pi(u), i(3)Pi(g), and I(1)Pi(g), of the hydrogen molecule
      at a single internuclear distance specific to each state. With the use of the
      analytical energy gradient, the present calculations yield new, lowest-to-date,
      variational energy upper bounds for all four states.

PMID- 23556704
TI  - Hyperfine interaction mechanism of magnetic field effects in sequential
      fluorophore and exciplex fluorescence.
AB  - The magnetic field effect on the fluorescence of the photoexcited electron
      acceptor, (1)A*, and the exciplex, (1)[D(+delta)A(-delta)] formed at contact of
      (1)A* with an electron donor (1)D, is theoretically explored in the framework of
      Integral Encounter Theory. It is assumed that the excited fluorophore is
      equilibrated with the exciplex that reversibly dissociates into the radical-ion
      pair. The magnetic field sensitive stage is the spin conversion in the resulting
      geminate radical-ion pair, (1, 3)[D(+)...A(-)] that proceeds due to hyperfine
      interaction. We confirm our earlier conclusion (obtained with a rate description
      of spin conversion) that in the model with a single nucleus spin 1/2 the
      magnitude of the Magnetic Field Effect (MFE) also vanishes in the opposite limits
      of low and high dielectric permittivity of the solvent. Moreover, it is shown
      that MFE being positive at small hyperfine interaction A, first increases with A
      but approaching the maximum starts to decrease and even changes the sign.

PMID- 23556705
TI  - Direct evaluation of the saddle splay modulus of a liquid-liquid interface using
      the classical mean field lattice model.
AB  - We study the curvature dependence of the liquid-liquid (liquid-gas) interface
      using the well-known mean field lattice model to estimate its rigidity
      parameters. The gaussian or saddle-splay modulus is found by evaluating the
      curvature energy of an interface onto which a saddle shape is imposed as this
      occurs in an Im3m cubic phase. The resulting values are consistent with those
      found by the classical indirect route, wherein the gaussian bending modulus
      results from combining the curvature dependences of the interfacial tension in
      cylindrical and spherical geometries.

PMID- 23556707
TI  - Lattice Boltzmann implementation of the three-dimensional Ben-Naim potential for
      water-like fluids.
AB  - We develop a three-dimensional lattice Boltzmann (LB) model accounting for
      directional interactions between water-like molecules, based on the so-called Ben
      Naim (BN) potential [A. Ben-Naim, Molecular Theory of Water and Aqueous
      Solutions: Part I: Understanding Water (World Scientific Publishing Company,
      2010); "Statistical mechanics of 'waterlike' particles in two dimensions. I.
      Physical model and application of the Percus-Yevick equation," J. Chem. Phys. 54,
      3682 (1971)]. The water-like molecules are represented by rigid tetrahedra, with
      two donors and two acceptors at the corners and interacting with neighboring
      tetrahedra, sitting on the nodes of a regular lattice. The tetrahedra are free to
      rotate about their centers under the drive of the torque arising from the
      interparticle potential. The orientations of the water molecules are evolved in
      time via an overdamped Langevin dynamics for the torque, which is solved by means
      of a quaternion technique. The resulting advection-diffusion-reaction equation
      for the quaternion components is solved by a LB method, acting as a dynamic
      minimizer for the global energy of the fluid. By adding thermal fluctuations to
      the torque equation, the model is shown to reproduce some microscopic features of
      real water, such as an average number of hydrogen bonds per molecules (HBs)
      between 3 and 4, in a qualitative agreement with microscopic water models. Albeit
      slower than a standard LB solver for ordinary fluids, the present scheme opens up
      potentially far-reaching scenarios for multiscale applications based on a coarse
      grained representation of the water solvent.

PMID- 23556706
TI  - An optimized semiclassical approximation for vibrational response functions.
AB  - The observables of multidimensional infrared spectroscopy may be calculated from
      nonlinear vibrational response functions. Fully quantum dynamical calculations of
      vibrational response functions are generally impractical, while completely
      classical calculations are qualitatively incorrect at long times. These
      challenges motivate the development of semiclassical approximations to quantum
      mechanics, which use classical mechanical information to reconstruct quantum
      effects. The mean-trajectory (MT) approximation is a semiclassical approach to
      quantum vibrational response functions employing classical trajectories linked by
      deterministic transitions representing the effects of the radiation-matter
      interaction. Previous application of the MT approximation to the third-order
      response function R(3)(t3, t2, t1) demonstrated that the method quantitatively
      describes the coherence dynamics of the t3 and t1 evolution times, but is
      qualitatively incorrect for the waiting-time t2 period. Here we develop an
      optimized version of the MT approximation by elucidating the connection between
      this semiclassical approach and the double-sided Feynman diagrams (2FD) that
      represent the quantum response. Establishing the direct connection between 2FD
      and semiclassical paths motivates a systematic derivation of an optimized MT
      approximation (OMT). The OMT uses classical mechanical inputs to accurately
      reproduce quantum dynamics associated with all three propagation times of the
      third-order vibrational response function.

PMID- 23556708
TI  - Complex-scaled equation-of-motion coupled-cluster method with single and double
      substitutions for autoionizing excited states: theory, implementation, and
      examples.
AB  - Theory and implementation of complex-scaled variant of equation-of-motion coupled
      cluster method for excitation energies with single and double substitutions (EOM
      EE-CCSD) is presented. The complex-scaling formalism extends the EOM-EE-CCSD
      model to resonance states, i.e., excited states that are metastable with respect
      to electron ejection. The method is applied to Feshbach resonances in atomic
      systems (He, H(-), and Be). The dependence of the results on one-electron basis
      set is quantified and analyzed. Energy decomposition and wave function analysis
      reveal that the origin of the dependence is in electron correlation, which is
      essential for the lifetime of Feshbach resonances. It is found that one-electron
      basis should be sufficiently flexible to describe radial and angular electron
      correlation in a balanced fashion and at different values of the scaling
      parameter, theta. Standard basis sets that are optimized for not-complex-scaled
      calculations (theta = 0) are not sufficiently flexible to describe the theta
      dependence of the wave functions even when heavily augmented by additional sets.

PMID- 23556709
TI  - Double excitations from modified Hartree Fock subsequent minimization scheme.
AB  - Doubly excited states have nowadays become important in technological
      applications, e.g., in increasing the efficiency of solar cells and therefore,
      their description using ab initio methods is a great theoretical challenge as
      double excitations cannot be described by linear response theories based on a
      single Slater determinant. In the present work we extend our recently developed
      Hartree-Fock (HF) approximation for calculating singly excited states [M. Tassi,
      I. Theophilou, and S. Thanos, Int. J. Quantum Chem. 113, 690 (2013)] in order to
      allow for the calculation of doubly excited states. We describe the double
      excitation as two holes in the subspace spanned from the occupied HF orbitals and
      two particles in the subspace of virtual HF orbitals. A subsequent minimization
      of the energy results to the determination of the spin orbitals of both the holes
      and the particles in the occupied and virtual subspaces, respectively. We test
      our method, for various atoms, H2 and polyene molecules which are known to have
      excitations presenting a significant double excitation character. Importantly,
      our approach is computationally inexpensive.

PMID- 23556710
TI  - Nonadiabatic anharmonic electron transfer.
AB  - The effect of an inner sphere, local mode vibration on an electron transfer is
      modeled using the nonadiabatic transition probability (rate) expression together
      with both the anharmonic Morse and the harmonic oscillator potential. For an
      anharmonic inner sphere mode, a variational analysis uses harmonic oscillator
      basis functions to overcome the difficulties evaluating Morse-model Franck-Condon
      overlap factors. Individual matrix elements are computed with the use of new,
      fast, robust, and flexible recurrence relations. The analysis therefore readily
      addresses changes in frequency and/or displacement of oscillator minimums in the
      different electron transfer states. Direct summation of the individual Boltzmann
      weighted Franck-Condon contributions avoids the limitations inherent in the use
      of the familiar high-temperature, gaussian form of the rate constant. The effect
      of harmonic versus anharmonic inner sphere modes on the electron transfer is
      readily seen, especially in the exoergic, inverted region. The behavior of the
      transition probability can also be displayed as a surface for all temperatures
      and values of the driving force/exoergicity Delta = -DeltaG. The temperature
      insensitivity of the transfer rate is clearly seen when the exoergicity equals
      the collective reorganization energy (Delta = Lambda(s)) along a maximum ln (w)
      vs. Delta ridge of the surface. The surface also reveals additional regions for
      Delta where ln (w) appears to be insensitive to temperature, or effectively
      activationless, for some kinds of inner sphere contributions.

PMID- 23556711
TI  - A combined quasi-continuum/Langevin equation approach to study the self-diffusion
      dynamics of confined fluids.
AB  - In this work, we combine our earlier proposed empirical potential based quasi
      continuum theory, (EQT) [A. V. Raghunathan, J. H. Park, and N. R. Aluru, J. Chem.
      Phys. 127, 174701 (2007)], which is a coarse-grained multiscale framework to
      predict the static structure of confined fluids, with a phenomenological Langevin
      equation to simulate the dynamics of confined fluids in thermal equilibrium. An
      attractive feature of this approach is that all the input parameters to the
      Langevin equation (mean force profile of the confined fluid and the static
      friction coefficient) can be determined using the outputs of the EQT and the self
      diffusivity data of the corresponding bulk fluid. The potential of mean force
      profile, which is a direct output from EQT is used to compute the mean force
      profile of the confined fluid. The density profile, which is also a direct output
      from EQT, along with the self-diffusivity data of the bulk fluid is used to
      determine the static friction coefficient of the confined fluid. We use this
      approach to compute the mean square displacement and survival probabilities of
      some important fluids such as carbon-dioxide, water, and Lennard-Jones argon
      confined inside slit pores. The predictions from the model are compared with
      those obtained using molecular dynamics simulations. This approach of combining
      EQT with a phenomenological Langevin equation provides a mathematically simple
      and computationally efficient means to study the impact of structural
      inhomogeneity on the self-diffusion dynamics of confined fluids.

PMID- 23556712
TI  - Spin-adaptation and redundancy in state-specific multireference perturbation
      theory.
AB  - Spin-adaptation of virtual functions in state-specific multireference
      perturbation theory is examined. Redundancy occurring among virtual functions
      generated by unitary group based excitation operators on a model-space function
      is handled by canonical orthogonalization. The treatment is found to remove non
      physical kinks observed earlier on potential energy surfaces. Sensitivity
      analysis of the new approach confirms the elimination of the drastic increase in
      singular values of sensitivity matrices, reported earlier.

PMID- 23556713
TI  - Quartic scaling second-order approximate coupled cluster singles and doubles via
      tensor hypercontraction: THC-CC2.
AB  - The second-order approximate coupled cluster singles and doubles method (CC2) is
      a valuable tool in electronic structure theory. Although the density fitting
      approximation has been successful in extending CC2 to larger molecules, it cannot
      address the steep O(N(5)) scaling with the number of basis functions, N. Here, we
      introduce the tensor hypercontraction (THC) approximation to CC2 (THC-CC2), which
      reduces the scaling to O(N(4)) and the storage requirements to O(N(2)). We
      present an algorithm to efficiently evaluate the THC-CC2 correlation energy and
      demonstrate its quartic scaling. This implementation of THC-CC2 uses a grid-based
      least-squares THC (LS-THC) approximation to the density-fitted electron repulsion
      integrals. The accuracy of the CC2 correlation energy under these approximations
      is shown to be suitable for most practical applications.

PMID- 23556714
TI  - Semilocal and hybrid density embedding calculations of ground-state charge
      transfer complexes.
AB  - We apply the frozen density embedding method, using a full relaxation of embedded
      densities through a freeze-and-thaw procedure, to study the electronic structure
      of several benchmark ground-state charge-transfer complexes, in order to assess
      the merits and limitations of the approach for this class of systems. The
      calculations are performed using both semilocal and hybrid exchange-correlation
      (XC) functionals. The results show that embedding calculations using semilocal XC
      functionals yield rather large deviations with respect to the corresponding
      supermolecular calculations. Due to a large error cancellation effect, however,
      they can often provide a relatively good description of the electronic structure
      of charge-transfer complexes, in contrast to supermolecular calculations
      performed at the same level of theory. On the contrary, when hybrid XC
      functionals are employed, both embedding and supermolecular calculations agree
      very well with each other and with the reference benchmark results. In
      conclusion, for the study of ground-state charge-transfer complexes via embedding
      calculations hybrid XC functionals are the method of choice due to their higher
      reliability and superior performance.

PMID- 23556715
TI  - Accurate prediction of nuclear magnetic resonance shielding constants: towards
      the accuracy of CCSD(T) complete basis set limit.
AB  - In this work, we have calculated the nuclear magnetic resonance (NMR) shielding
      constants for 42 molecules at the levels of second order Moller-Plesset
      perturbation (MP2) and coupled-cluster singles and doubles model augmented by
      perturbative corrections for triple excitations CCSD(T). Basis set extrapolations
      to the complete basis set (CBS) limit have been performed. A focal-point analysis
      method for magnetic parameters was proposed here, which adds the
      [sigma(e)(CCSD(T)) - sigma(e)(MP2)] difference to the MP2/CBS number to
      approximate the corresponding CCSD(T)/CBS value. Systematical comparison has
      demonstrated the usefulness of this FPA-M/CBS scheme.

PMID- 23556716
TI  - Topology of classical molecular optimal control landscapes in phase space.
AB  - Optimal control of molecular dynamics is commonly expressed from a quantum
      mechanical perspective. However, in most contexts the preponderance of molecular
      dynamics studies utilize classical mechanical models. This paper treats laser
      driven optimal control of molecular dynamics in a classical framework. We
      consider the objective of steering a molecular system from an initial point in
      phase space to a target point, subject to the dynamic constraint of Hamilton's
      equations. The classical control landscape corresponding to this objective is a
      functional of the control field, and the topology of the landscape is analyzed
      through its gradient and Hessian with respect to the control. Under specific
      assumptions on the regularity of the control fields, the classical control
      landscape is found to be free of traps that could hinder reaching the objective.
      The Hessian associated with an optimal control field is shown to have finite
      rank, indicating the presence of an inherent degree of robustness to control
      noise. Extensive numerical simulations are performed to illustrate the
      theoretical principles on (a) a model diatomic molecule, (b) two coupled Morse
      oscillators, and (c) a chaotic system with a coupled quartic oscillator,
      confirming the absence of traps in the classical control landscape. We compare
      the classical formulation with the mathematically analogous quantum state-to
      state transition probability control landscape.

PMID- 23556717
TI  - Vibrational and electronic excitations in fluorinated ethene cations from the
      ground up.
AB  - Valence threshold photoelectron spectra of four fluorinated ethenes; C2H3F, 1,1
      C2H2F2, C2HF3, and C2F4 were recorded at the Swiss Light Source with 0.002 eV
      resolution. The adiabatic ionization energies were found to be 10.364 +/- 0.007,
      10.303 +/- 0.005, 10.138 +/- 0.007, and 10.110 +/- 0.009 eV, respectively. The
      electronic ground state of each cation shows well-resolved multi-component
      vibrational progressions, the dominant transitions being in the C=C stretching
      mode. Density functional theory based Franck-Condon simulations are used to model
      the vibrational structure and assign the spectra, sometimes revising previous
      assignments. An additional vibrational progression in the first photoelectron
      band of 1,1-C2H2F2 indicates that the ground electronic state of the molecular
      ion is no longer planar. It is shown that ab initio vibrational frequencies
      together with the observed vibrational spacings do not always suffice to assign
      the spectra. In addition to symmetry rules governing the transitions, it is often
      essential to consider the associated Franck-Condon factors explicitly. Ionization
      to higher lying excited valence electronic states were also recorded by threshold
      ionization up to 23 eV photon energy. Equation-of-motion coupled cluster with
      single and double substitutions for ionization potential (EOM-IP-CCSD/cc-pVTZ)
      calculations confirmed historic electronic state assignments, and untangled the
      ever more congested spectra with increasing F-substitution. Previous attempts at
      illuminating the intriguing dissociative photoionization mechanism of fluorinated
      ethenes are reconsidered in view of new computational and experimental results.
      We show how non-statistical F-atom loss from C2H3F(+) is decoupled from the
      ground state dissociation dynamics in the energy range of its C state. Both the
      statistical and the non-statistical dissociation processes are mediated by a
      plethora of conical intersections.

PMID- 23556718
TI  - Ab initio studies of atomic properties and experimental behavior of element 119
      and its lighter homologs.
AB  - Static dipole polarizabilities of element 119 and its singly charged cation are
      calculated, along with those of its lighter homologs, Cs and Fr. Relativity is
      treated within the 4-component Dirac-Coulomb formalism and electron correlation
      is included by the single reference coupled cluster approach with single, double,
      and perturbative triple excitations (CCSD(T)). Very good agreement with available
      experimental values is obtained for Cs, lending credence to the predictions for
      Fr and element 119. The atomic properties in group-1 are largely determined by
      the valence ns orbital, which experiences relativistic stabilization and
      contraction in the heavier elements. As a result, element 119 is predicted to
      have a relatively low polarizability (169.7 a.u.), comparable to that of Na. The
      adsorption enthalpy of element 119 on Teflon, which is important for possible
      future experimental studies of this element, is estimated as 17.6 kJ/mol, the
      lowest among the atoms considered here.

PMID- 23556719
TI  - Photoelectron spectroscopy of the aluminum hydride anions: AlH2(-), AlH3(-),
      Al2H6(-), Al3H9(-), and Al4H12(-).
AB  - We report measurements of the negative ion photoelectron spectra of the simple
      aluminum hydride anions: AlH2(-), AlH3(-), Al2H6(-), Al3H9(-), and Al4H12(-).
      From these spectra, we measured the vertical detachment energies of the anions,
      and we estimated the electron affinities of their neutral counterparts. Our
      results for AlH2(-), AlH3(-), and Al2H6(-) were also compared with previous
      predictions by theory.

PMID- 23556720
TI  - Ion imaging study of dissociative charge transfer in the N2(+) + CH4 system.
AB  - The velocity map ion imaging method is applied to the dissociative charge
      transfer reactions of N2(+) with CH4 studied in crossed beams. The velocity space
      images are collected at four collision energies between 0.5 and 1.5 eV, providing
      both product kinetic energy and angular distributions for the reaction products
      CH3(+) and CH2(+). The general shapes of the images are consistent with long
      range electron transfer from CH4 to N2(+) preceding dissociation, and product
      kinetic energy distributions are consistent with energy resonance in the initial
      electron transfer step. The branching ratio for CH3(+):CH2(+) is 85:15 over the
      full collision energy range, consistent with literature reports.

PMID- 23556721
TI  - Vibrational Raman spectra of hydrogen clathrate hydrates from density functional
      theory.
AB  - Hydrogen clathrate hydrates are promising sources of clean energy and are known
      to exist in a sII hydrate lattice, which consists of H2 molecules in dodecahedron
      (5(12)) and hexakaidecahedron (5(12)6(4)) water cages. The formation of these
      hydrates which occur in extreme thermodynamic conditions is known to be
      considerably reduced by an inclusion of tetrahydrofuran (THF) in cages of these
      hydrate lattice. In this present work, we employ the density functional theory
      with a dispersion corrected (B97-D) functional to characterize vibrational Raman
      modes in the cages of pure and THF doped hydrogen clathrate hydrates. Our
      calculations show that the symmetric stretch of the H2 molecule in the
      5(12)6(4)H2.THF cage is blueshifted compared to the 5(12)6(4)H2 cage. However,
      all vibrational modes of water molecules are redshifted which suggest reduced
      interaction between the H2 molecule and water molecules in the 5(12)6(4)H2.THF
      cage. The symmetric and asymmetric O-H stretch of water molecules in 5(12)H2,
      5(12)6(4)H2, and 5(12)6(4)H2.THF cages are redshifted compared with the
      corresponding guest free cages due to interactions between encapsulated H2
      molecules and water molecules of the cages. The low frequency modes contain
      contributions from contraction and expansion of water cages and vibration of
      water molecules due to hydrogen bonding and these modes could possibly play an
      important role in the formation of the hydrate lattice.

PMID- 23556722
TI  - Ionization of large homogeneous and heterogeneous clusters generated in acetylene
      Ar expansions: cluster ion polymerization.
AB  - Pure acetylene and mixed Ar-acetylene clusters are formed in supersonic
      expansions of acetylene/argon mixtures and analysed using reflectron time-of
      flight mass spectrometer with variable electron energy ionization source.
      Acetylene clusters composed of more than a hundred acetylene molecules are
      generated at the acetylene concentration of ~8%, while mixed species are produced
      at low concentrations (~0.7%). The electron energy dependence of the mass spectra
      revealed the ionization process mechanisms in clusters. The ionization above the
      threshold for acetylene molecule of 11.5 eV results in the main ionic fragment
      progression (C2H2)n(+). At the electron energies >=21.5 eV above the CH+CH(+)
      dissociative ionization limit of acetylene the fragment ions nominally labelled
      as (C2H2)nCH(+), n >= 2, are observed. For n <= 7 these fragments correspond to
      covalently bound ionic structures as suggested by the observed strong
      dehydrogenation [(C2H2)n - k * H](+) and [(C2H2)nCH - k * H](+). The
      dehydrogenation is significantly reduced in the mixed clusters where evaporation
      of Ar instead of hydrogen can stabilize the nascent molecular ion. The C3H3(+)
      ion was previously assigned to originate from the benzene molecular ion; however,
      the low appearance energy of ~13.7 eV indicates that a less rigid covalently
      bound structure of C6H6(+) ion must also be formed upon the acetylene cluster
      electron ionization. The appearance energy of Arn(C2H2)(+) fragments above ~15.1
      eV indicates that the argon ionization is the first step in the fragment ion
      production, and the appearance energy of Arn>=2(C2H2)m>=2(+) at ~13.7 eV is
      discussed in terms of an exciton transfer mechanism.

PMID- 23556723
TI  - Morphology of collisional nonlinear spectra in H2-Kr and H2-Xe mixtures.
AB  - This article reports new results of theoretical and numerical studies of spectral
      features of the collision-induced hyper-Rayleigh light scattered in dihydrogen
      noble gas (H2-Rg) mixtures. The most massive and polarizable scattering
      supermolecules with Rg = Kr and Xe have been added to the previously considered
      systems in order to gain a more complete insight into the evolution of the
      spectral properties. The symmetry adapted components of the first collisional
      hyperpolarizabilities are obtained by means of the quantum chemistry numerical
      routines supplemented with appropriate theoretical methods. Roto-translational
      spectral lines are calculated on the grounds of the quantum-mechanical as well as
      semi-classical approach. The role of particular hyperpolarizability components in
      forming the line shapes is discussed. The intensities of the lines are compared
      with those obtained for less massive scatterers. Advantages of prospective
      application of the new scattering systems for experimental detection of the
      nonlinear collisional effects are indicated.

PMID- 23556725
TI  - Full-dimensional quantum calculations of the vibrational states of H5(+).
AB  - Full-dimensional quantum calculations of the vibrational states of H5(+) have
      been performed on the accurate potential energy surface developed by Xie et al.
      [J. Chem. Phys. 122, 224307 (2005)]. The zero point energies of H5(+), H4D(+),
      D4H(+), and D5(+) and their ground-state geometries are presented and compared
      with earlier theoretical results. The first 10 low-lying excited states of H5(+)
      are assigned to the fundamental, overtone, and combination of the H2-H3(+)
      stretch, the shared proton hopping and the out-of-plane torsion. The ground-state
      torsional tunneling splitting, the fundamental of the photon hopping mode and the
      first overtone of the torsion mode are 87.3 cm(-1), 354.4 cm(-1), and 444.0 cm(
      1), respectively. All of these values agree well with the diffusion Monte Carlo
      and multi-configuration time-dependent Hartree results where available.

PMID- 23556724
TI  - High temperature reaction kinetics of CN(v = 0) with C2H4 and C2H6 and
      vibrational relaxation of CN(v = 1) with Ar and He.
AB  - The investigation of the chemical complexity of hot environments, ranging from
      combustion flames to circumstellar envelopes of evolved stars, relies on the
      determination of the reaction kinetics and product branching ratio. We have
      designed a chemical reactor for the exploration of high temperature chemistry.
      This apparatus is employed in the present study to measure the reaction kinetics
      of the CN radical with C2H4 and C2H6 over the 300-1200 K temperature range. In
      our setup and in some environments, the CN radical is partially produced in a
      vibrationally excited state, before relaxing by collision with the surrounding
      gas. We complement the experimental kinetic studies of hydrocarbons reactions
      with CN(v = 0) with a theoretical study of vibrational relaxation of CN(v = 1) by
      He and Ar atoms, the main collisional partners in our apparatus. Calculations are
      carried out to determine the collisional elastic and inelastic cross sections
      versus the kinetic energy as well as the corresponding vibrationally elastic and
      inelastic rate coefficients. The results are compared with empirical calculations
      and with a few experimental observations. The range of validity of the empirical
      model is discussed and potential applications sketched.

PMID- 23556726
TI  - Resonance Regge poles and the state-to-state F + H2 reaction: QP decomposition,
      parametrized S matrix, and semiclassical complex angular momentum analysis of the
      angular scattering.
AB  - Three new contributions to the complex angular momentum (CAM) theory of
      differential cross sections (DCSs) for chemical reactions are reported. They
      exploit recent advances in the Pade reconstruction of a scattering (S) matrix in
      a region surrounding the ReJ axis, where J is the total angular momentum quantum
      variable, starting from the discrete values, J = 0, 1, 2, .... In particular, use
      is made of Pade continuations obtained by Sokolovski, Castillo, and Tully [Chem.
      Phys. Lett. 313, 225 (1999)] for the S matrix of the benchmark F + H2(v(i) = 0,
      j(i) = 0, m(i) = 0) -> FH(v(f) = 3, j(f) = 3, m(f) = 0) + H reaction. Here v(i),
      j(i), m(i) and v(f), j(f), m(f) are the initial and final vibrational,
      rotational, and helicity quantum numbers, respectively. The three contributions
      are: (1) A new exact decomposition of the partial wave (PW) S matrix is
      introduced, which is called the QP decomposition. The P part contains information
      on the Regge poles. The Q part is then constructed exactly by subtracting a
      rapidly oscillating phase and the PW P matrix from the input PW S matrix. After a
      simple modification, it is found that the corresponding scattering subamplitudes
      provide insight into the angular-scattering dynamics using simple partial wave
      series (PWS) computations. It is shown that the leading n = 0 Regge pole
      contributes to the small-angle scattering in the centre-of-mass frame. (2) The Q
      matrix part of the QP decomposition has simpler properties than the input S
      matrix. This fact is exploited to deduce a parametrized (analytic) formula for
      the PW S matrix in which all terms have a direct physical interpretation. This is
      a long sort-after goal in reaction dynamics, and in particular for the state-to
      state F + H2 reaction. (3) The first definitive test is reported for the accuracy
      of a uniform semiclassical (asymptotic) CAM theory for a DCS based on the Watson
      transformation. The parametrized S matrix obtained in contribution (2) is used in
      both the PW and semiclassical parts of the calculation. Powerful uniform
      asymptotic approximations are employed for the background integral; they allow
      for the proximity of a Regge pole and a saddle point. The CAM DCS agrees well
      with the PWS DCS, across the whole angular range, except close to the forward and
      backward directions, where, as expected, the CAM theory becomes non-uniform. At
      small angles, theta(R) ? 40 degrees , the PWS DCS can be reproduced using a
      nearside semiclassical subamplitude, which allows for a pole being close to a
      saddle point, plus the farside surface wave of the n = 0 pole sub-subamplitude,
      with the oscillations in the DCS arising from nearside-farside interference. This
      proves that the n = 0 Regge resonance pole contributes to the small-angle
      scattering.

PMID- 23556727
TI  - Carbon X-ray absorption spectra of fluoroethenes and acetone: a study at the
      coupled cluster, density functional, and static-exchange levels of theory.
AB  - Near carbon K-edge X-ray absorption fine structure spectra of a series of
      fluorine-substituted ethenes and acetone have been studied using coupled cluster
      and density functional theory (DFT) polarization propagator methods, as well as
      the static-exchange (STEX) approach. With the complex polarization propagator
      (CPP) implemented in coupled cluster theory, relaxation effects following the
      excitation of core electrons are accounted for in terms of electron correlation,
      enabling a systematic convergence of these effects with respect to electron
      excitations in the cluster operator. Coupled cluster results have been used as
      benchmarks for the assessment of propagator methods in DFT as well as the state
      specific static-exchange approach. Calculations on ethene and 1,1-difluoroethene
      illustrate the possibility of using nonrelativistic coupled cluster singles and
      doubles (CCSD) with additional effects of electron correlation and relativity
      added as scalar shifts in energetics. It has been demonstrated that CPP spectra
      obtained with coupled cluster singles and approximate doubles (CC2), CCSD, and
      DFT (with a Coulomb attenuated exchange-correlation functional) yield excellent
      predictions of chemical shifts for vinylfluoride, 1,1-difluoroethene,
      trifluoroethene, as well as good spectral features for acetone in the case of
      CCSD and DFT. Following this, CPP-DFT is considered to be a viable option for the
      calculation of X-ray absorption spectra of larger pi-conjugated systems, and CC2
      is deemed applicable for chemical shifts but not for studies of fine structure
      features. The CCSD method as well as the more approximate CC2 method are shown to
      yield spectral features relating to pi*-resonances in good agreement with
      experiment, not only for the aforementioned molecules but also for ethene, cis
      1,2-difluoroethene, and tetrafluoroethene. The STEX approach is shown to
      underestimate pi*-peak separations due to spectral compressions, a characteristic
      which is inherent to this method.

PMID- 23556728
TI  - Vibrational and vibronic spectra of tryptamine conformers.
AB  - Conformation-specific ionization-detected stimulated Raman spectra, including
      both Raman loss and Raman gain lines, along with visible-visible-ultraviolet hole
      burning spectra of tryptamine (TRA) conformers have been measured simultaneously,
      with the aim of obtaining new data for identifying them. The slightly different
      orientations of the ethylamine side chain relative to the indole lead to unique
      spectral signatures, pointing to the presence of seven TRA conformers in the
      molecular beam. Comparison of ionization-loss stimulated Raman spectra to
      computationally scaled harmonic Raman spectra, especially in the alkyl C-H and
      amine N-H stretch regions together with the retrieved information on the
      stabilities of the TRA conformers assisted their characterization and structural
      identification. The prospects and limitations of using these spectroscopic
      methods as potential conformational probes of flexible molecules are discussed.

PMID- 23556729
TI  - The molecular frame electric dipole moment and hyperfine interactions in hafnium
      fluoride, HfF.
AB  - The (1,0) [17.9]2.5-X(2)Delta(3/2) band of hafnium monofluoride (HfF) has been
      recorded using high-resolution laser-induced fluorescence spectroscopy both field
      free and in the presence of a static electric field. The field-free spectra of
      (177)HfF, (179)HfF, and (180)HfF were modeled to generate a set of fine and
      hyperfine parameter for the X(2)Delta(3/2)(v = 0) and [17.9]2.5 (v = 1) states.
      The observed optical Stark shifts for the (180)HfF isotopologue were analyzed to
      produce the molecular frame electric dipole moments of 1.66(1) D and 0.419(7) D
      for the X(2)Delta(3/2) and [17.9]2.5 state, respectively. Both the generalized
      effective core potential and all-electron four component approaches were used in
      ab initio calculations to predict the properties of ground state HfF including
      equilibrium distance, dipole moments, quadrupole coupling, and magnetic hyperfine
      constants.

PMID- 23556730
TI  - Global sampling of the photochemical reaction paths of bromoform by ultrafast
      deep-UV through near-IR transient absorption and ab initio multiconfigurational
      calculations.
AB  - Ultrafast deep-ultraviolet through near infrared (210-950 nm) transient
      absorption spectroscopy complemented by ab initio multiconfigurational
      calculations offers a global description of the photochemical reaction pathways
      of bromoform following 255-nm excitation in methylcyclohexane and acetonitrile
      solutions. Photoexcitation of CHBr3 leads to the ground-state iso-CHBr3 product
      in a large quantum yield (~35%), formed through two different mechanisms:
      concerted excited-state isomerization and cage-induced isomerization through the
      recombination of the nascent radical pair. These two processes take place on
      different time scales of tens of femtoseconds and several picoseconds,
      respectively. The novel ultrafast direct isomerization pathway proposed herein is
      consistent with the occurrence of a conical intersection between the first
      excited singlet state of CHBr3 and the ground electronic state of iso-CHBr3.
      Complete active space self-consistent field calculations characterize this
      singularity in the vicinity of a second order saddle point on the ground state
      which connects the two isomer forms. For cage-induced isomerization, both the
      formation of the nascent radical pair and its subsequent collapse into ground
      state iso-CHBr3 are directly monitored through the deep-ultraviolet absorption
      signatures of the radical species. In both mechanisms, the optically active
      (i.e., those with largest Franck-Condon factors) C-Br-Br bending and Br-Br
      stretching modes of ground-state iso-CHBr3 have the largest projection on the
      reaction coordinate, enabling us to trace the structural changes accompanying
      vibrational relaxation of the non-equilibrated isomers through transient
      absorption dynamics. The iso-CHBr3 photoproduct is stable in methylcyclohexane,
      but undergoes either facile thermal isomerization to the parent CHBr3 structure
      through a cyclic transition state stabilized by the polar acetonitrile medium
      (~300-ps lifetime), and hydrolysis in the presence of water.

PMID- 23556731
TI  - A thermodynamic derivation of the reciprocal relations.
AB  - Starting with the continuity and Smoluchowski equations, we write the mass flux
      for a system out of equilibrium in terms of the physicochemical potential MU(g).
      MU(g) is a coarse-grained analog of the chemical potential in the presence of
      forces that drive the system out of equilibrium. The expression for flux in terms
      of MU(g) allows for a macroscopic derivation of the Onsager reciprocal relations
      for the case of transport by diffusion and drift in single or multi-component
      systems, without recourse to microscopic fluctuations or equations of motion.
      Transport coefficients for any time reversal-invariant properties now are
      expressed in terms of only partial molar derivatives and mobilities (diffusion
      coefficients). The thermodynamic derivation cannot treat time reversal.

PMID- 23556732
TI  - Hyperfine coupling of the hydrogen atom in high temperature water.
AB  - The hyperfine coupling constant of the hydrogen atom has been measured in
      pressurized liquid water up to 300  degrees C. The reduced constant
      A(water)/A(vacuum) is 0.9939 at room temperature, and decreases to a minimum of
      0.9918 at 240  degrees C. The reduced constant then increases at higher
      temperature. The g-factor is 2.002244(10) at room temperature and decreases to
      2.00221(1) at 240  degrees C. The change in g-factor is proportional to the
      change in hyperfine coupling. The behavior below 110  degrees C is in excellent
      agreement with a previously proposed model in which the H atom is confined to a
      harmonic solvent cage, and vibrations within the cage mix "p-type" character into
      the wavefunction, resulting inA(water)/A(vacuum) < 1. The harmonic model breaks
      down above 130  degrees C. We demonstrate that a classical binary collision model
      using approximate partial molar volume information can recover the observed
      minima near 240  degrees C.

PMID- 23556733
TI  - Water proton configurations in structures I, II, and H clathrate hydrate unit
      cells.
AB  - Position and orientation of water protons need to be specified when the molecular
      simulation studies are performed for clathrate hydrates. Positions of oxygen
      atoms in water are experimentally determined by X-ray diffraction analysis of
      clathrate hydrate structures, but positions of water hydrogen atoms in the
      lattice are disordered. This study reports a determination of the water proton
      coordinates in unit cell of structure I (sI), II (sII), and H (sH) clathrate
      hydrates that satisfy the ice rules, have the lowest potential energy
      configuration for the protons, and give a net zero dipole moment. Possible proton
      coordinates in the unit cell were chosen by analyzing the symmetry of protons on
      the hexagonal or pentagonal faces in the hydrate cages and generating all
      possible proton distributions which satisfy the ice rules. We found that in the
      sI and sII unit cells, proton distributions with small net dipole moments have
      fairly narrow potential energy spreads of about 1 kJ/mol. The total Coulomb
      potential on a test unit charge placed in the cage center for the minimum
      energy/minimum dipole unit cell configurations was calculated. In the sI small
      cages, the Coulomb potential energy spread in each class of cage is less than 0.1
      kJ/mol, while the potential energy spread increases to values up to 6 kJ/mol in
      sH and 15 kJ/mol in the sII cages. The guest environments inside the cages can
      therefore be substantially different in the sII case. Cartesian coordinates for
      oxygen and hydrogen atoms in the sI, sII, and sH unit cells are reported for
      reference.

PMID- 23556734
TI  - Non-monotonic size dependence of diffusion and levitation effect: a mode-coupling
      theory analysis.
AB  - We present a study of diffusion of small tagged particles in a solvent, using
      mode coupling theory (MCT) analysis and computer simulations. The study is
      carried out for various interaction potentials. For the first time, using MCT, it
      is shown that only for strongly attractive interaction potential with allowing
      interpenetration between the solute-solvent pair the diffusion exhibits a non
      monotonic solute size dependence which has earlier been reported in simulation
      studies [P. K. Ghorai and S. Yashonath, J. Phys. Chem. B 109, 5824-5835 (2005)].
      For weak attractive and repulsive potential the solute size dependence of
      diffusion shows monotonic behaviour. It is also found that for systems where the
      interaction potential does not allow solute-solvent interpenetration, the solute
      cannot explore the neck of the solvent cage. Thus these systems even with strong
      attractive interaction will never show any non-monotonic size dependence of
      diffusion. This non-monotonic size dependence of diffusion has earlier been
      connected to levitation effect [S. Yashonath and P. Santikary, J. Phys. Chem. 98,
      6368 (1994)]. We also show that although levitation is a dynamic phenomena, the
      effect of levitation can be obtained in the static radial distribution function.

PMID- 23556735
TI  - 1H relaxation dispersion in solutions of nitroxide radicals: influence of
      electron spin relaxation.
AB  - The work presents a theory of nuclear ((1)H) spin-lattice relaxation dispersion
      for solutions of (15)N and (14)N radicals, including electron spin relaxation
      effects. The theory is a generalization of the approach presented by Kruk et al.
      [J. Chem. Phys. 137, 044512 (2012)]. The electron spin relaxation is attributed
      to the anisotropic part of the electron spin-nitrogen spin hyperfine interaction
      modulated by rotational dynamics of the paramagnetic molecule, and described by
      means of Redfield relaxation theory. The (1)H relaxation is caused by electron
      spin-proton spin dipole-dipole interactions which are modulated by relative
      translational motion of the solvent and solute molecules. The spectral density
      characterizing the translational dynamics is described by the force-free-hard
      sphere model. The electronic relaxation influences the (1)H relaxation by
      contributing to the fluctuations of the inter-molecular dipolar interactions. The
      developed theory is tested against (1)H spin-lattice relaxation dispersion data
      for glycerol solutions of 4-oxo-TEMPO-d16-(15)N and 4-oxo-TEMPO-d16-(14)N
      covering the frequency range of 10 kHz-20 MHz. The studies are carried out as a
      function of temperature starting at 328 K and going down to 290 K. The theory
      gives a consistent overall interpretation of the experimental data for both (14)N
      and (15)N systems and explains the features of (1)H relaxation dispersion
      resulting from the electron spin relaxation.

PMID- 23556736
TI  - Nonequilibrium molecular dynamics simulation of pressure-driven water transport
      through modified CNT membranes.
AB  - Nonequilibrium molecular dynamics (NEMD) simulations are presented to investigate
      the effect of water-membrane interactions on the transport properties of pressure
      driven water flow passing through carbon nanotube (CNT) membranes. The CNT
      membrane is modified with different physical properties to alter the van der
      Waals interactions or the electrostatic interactions between water molecules and
      the CNT membranes. The unmodified and modified CNT membranes are models of
      simplified nanofiltration (NF) membranes at operating conditions consistent with
      real NF systems. All NEMD simulations are run with constant pressure difference
      (8.0 MPa) temperature (300 K), constant pore size (0.643 nm radius for CNT (12,
      12)), and membrane thickness (6.0 nm). The water flow rate, density, and velocity
      (in flow direction) distributions are obtained by analyzing the NEMD simulation
      results to compare transport through the modified and unmodified CNT membranes.
      The pressure-driven water flow through CNT membranes is from 11 to 21 times
      faster than predicted by the Navier-Stokes equations. For water passing through
      the modified membrane with stronger van der Waals or electrostatic interactions,
      the fast flow is reduced giving lower flow rates and velocities. These
      investigations show the effect of water-CNT membrane interactions on water
      transport under NF operating conditions. This work can help provide and improve
      the understanding of how these membrane characteristics affect membrane
      performance for real NF processes.

PMID- 23556737
TI  - Monoxide carbon frequency shift as a tool for the characterization of TiO2
      surfaces: insights from first principles spectroscopy.
AB  - The adsorption and vibrational frequency of CO on defective and undefective
      titanium dioxide surfaces is examined applying first-principles molecular
      dynamics simulations. In particular, the vibrational frequencies are obtained
      beyond the harmonic approximation, through the time correlation functions of the
      atomic trajectories. In agreement with experiments, at low CO coverages we find
      an upshift in the vibration frequency with respect to the free CO molecule, of 45
      and 35 cm(-1) on the stoichiometric rutile (110) and anatase (101) faces,
      respectively. A band falling 8 cm(-1) below the frequency corresponding to the
      perfect face is observed for the reduced rutile (110) surface in the low vacancy
      concentration limit, where the adsorption is favored on Ti(4+) sites. At a higher
      density of defects, adsorption on Ti(3+) sites becomes more stable, accompanied
      by a downshift in the stretching band. In the case of anatase (101), we analyze
      the effect of subsurface oxygen vacancies, which have been shown to be
      predominant in this material. Interestingly, we find that the adsorption of CO on
      five coordinate Ti atoms placed over subsurface vacancies is favored with respect
      to other Ti(4+) sites (7.25 against 6.95 kcal/mol), exhibiting a vibrational
      redshift of 20 cm(-1). These results provide the basis to quantitatively assess
      the degree of reduction of rutile and anatase surfaces via IR spectroscopy, and
      at the same time allow for the assignment of characteristic bands in the CO
      spectra on TiO2 whose origin has remained ambiguous.

PMID- 23556738
TI  - Structure and chemical reactivity of the polar three-fold surfaces of GaPd: a
      density-functional study.
AB  - The polar threefold surfaces of the GaPd compound crystallizing in the B20 (FeSi
      type) structure (space group P2(1)3) have been investigated using density
      functional methods. Because of the lack of inversion symmetry the B20 structure
      exists in two enantiomorphic forms denoted as A and B. The threefold {111}
      surfaces have polar character. In both nonequivalent (111) and (111) directions
      several surface terminations differing in structure and chemical composition are
      possible. The formation of the threefold surfaces has been studied by simulated
      cleavage experiments and by calculations of the surface energies. Because of the
      polar character of the threefold surfaces calculations for stoichiometric slabs
      permit only the determination of the average energy of the surfaces exposed on
      both sides of the slab. Calculations for nonstoichiometric slabs performed in the
      grand canonical ensemble yield differences of the surface energies for the
      possible terminations as a function of the chemical potential in the reactive
      atmosphere above the surface and predict a transition between Ga- and Pd
      terminated surfaces as a function of the chemical potential. The {100} surfaces
      are stoichiometric and uniquely defined. The calculated surface energies are
      identical to the average energies of the {100} surfaces of the pure metals. The
      {210} surfaces are also stoichiometric, with an energy very close to that of the
      {100} surfaces. Assuming that for the {111} surfaces the energies of different
      possible terminations are in a proportion equal to that of the concentration
      weighted energies of the {111} surfaces of the pure metals, surface energies for
      all possible {111} terminations may be calculated. The preferable termination
      perpendicular to the A<111> direction consists of a bilayer with three Ga atoms
      in the upper and three Pd atoms in the lower part. The surface energy of this
      termination further decreases if the Pd triplet is covered by additional Ga atom.
      Perpendicular to the A<111> direction the lowest energy has been found for a
      bilayer with three Ga atoms per surface cell in the upper layer and one Ga and
      one Pd in the lower part. The calculated surface energies are in agreement with a
      simulated cleavage experiment. However, cleavage does not result in the formation
      of the lowest-energy surfaces, because all possible {111} cleavage planes expose
      a low-energy surface on one, and a high-energy surface on the other side. The
      prediction of Ga-terminated surfaces has been tested against the available
      experimental information. The calculated surface electronic density of states is
      in very good agreement with photo-emission spectroscopy. Calculated STM images of
      the most stable surfaces agree with all details of the available experimental
      images. The chemical reactivity of the most stable surfaces has been studied by
      the adsorption of CO molecules. The adsorption energies and maximum coverages
      calculated for the Ga-terminated surfaces permit a reasonable interpretation of
      the observed thermal desorption spectra, whereas for the Pd-terminated surfaces
      the calculated adsorption energies are far too high.

PMID- 23556740
TI  - Knudsen layer formation in laser induced thermal desorption.
AB  - Laser induced thermal desorption of Xe atoms into vacuum from a metal surface
      following the nano-second pulsed laser heating was investigated by the time-of
      flight (TOF) measurement. The desorption flow was studied at a wide range of
      desorption flux by varying the initially prepared Xe coverage Theta (1 ML = 4.5 *
      10(18) atoms/m(2)). At Theta = 0.3 ML, the TOF of Xe was well represented by a
      Maxwell-Boltzmann velocity distribution, which is in good agreement with thermal
      desorption followed by collision-free flow. At Theta > 0.3 ML, the peak positions
      of the TOF spectra were shifted towards the smaller values and became constant at
      large Theta, which were well fitted with a shifted Maxwell-Boltzmann velocity
      distribution with a temperature TD and a stream velocity u. With TD fixed at 165
      K, u was found to increase from 80 to 125 m/s with increasing Theta from 1.2 to 4
      ML. At Theta > 4 ML, the value of u becomes constant at 125 m/s. The converging
      feature of u was found to be consistent with analytical predictions and simulated
      results based on the Knudsen layer formation theory. We found that the Knudsen
      layer formation in laser desorption is completed at Knudsen number Kn <0.39.

PMID- 23556739
TI  - Phonon thermal transport outside of local equilibrium in nanowires via molecular
      dynamics.
AB  - We study thermal transport through Pt nanowires that bridge planar contacts as a
      function of wire length and vibrational frequency of the contacts. When phonons
      in the contacts have lower average frequencies than those in the wires thermal
      transport occurs under conditions away from local equilibrium with low-frequency
      phonons experiencing a higher thermal gradient than high-frequency ones. This
      results in a size-dependent increase in the effective thermal conductivity of the
      wire with decreasing vibrational frequencies of the contacts. The interfacial
      resistivity when heat flows from the wire to the contact is also size-dependent
      and has the same physical origin in the lack of full equilibration in short
      nanowires. We develop a model based on a 1D atomic chain that captures the
      salient physics of the MD results.

PMID- 23556741
TI  - Electronic and optical properties of graphene and graphitic ZnO nanocomposite
      structures.
AB  - Electronic and optical properties of graphene and graphitic ZnO (G/g-ZnO)
      nanocomposites have been investigated with density functional theory. Graphene
      interacts overall weakly with g-ZnO monolayer via van der Waals interaction.
      There is no charge transfer between the graphene and g-ZnO monolayer, while a
      charge redistribution does happen within the graphene layer itself, forming well
      defined electron-hole puddles. When Al or Li is doped in the g-ZnO monolayer,
      substantial electron (n-type) and hole (p-type) doping can be induced in
      graphene, leading to well-separated electron-hole pairs at their interfaces.
      Improved optical properties in graphene/g-ZnO nanocomposite systems are also
      observed, with potential photocatalytic and photovoltaic applications.

PMID- 23556742
TI  - Grain boundary melting in ice.
AB  - We describe an optical scattering study of grain boundary premelting in water
      ice. Ubiquitous long ranged attractive polarization forces act to suppress grain
      boundary melting whereas repulsive forces originating in screened Coulomb
      interactions and classical colligative effects enhance it. The liquid enhancing
      effects can be manipulated by adding dopant ions to the system. For all measured
      grain boundaries this leads to increasing premelted film thickness with
      increasing electrolyte concentration. Although we understand that the interfacial
      surface charge densities q(s) and solute concentrations can potentially dominate
      the film thickness, we cannot directly measure them within a given grain
      boundary. Therefore, as a framework for interpreting the data we consider two
      appropriate q(s) dependent limits; one is dominated by the colligative effect and
      other is dominated by electrostatic interactions.

PMID- 23556743
TI  - Deposition of model chains on surfaces: anomalous relation between flux and
      stability.
AB  - Model chains are studied via Monte Carlo simulations which are deposited with a
      fixed flux on a substrate. They may represent, e.g., stiff lipophilic chains with
      an head group and tail groups mimicking the alkyl chain. After some subsequent
      fixed simulation time we determine the final energy as a function of flux and
      temperature. Surprisingly, in some range of temperature and flux the final energy
      increases with decreasing flux. The physical origin of this counterintuitive
      observation is elucidated. In contrast, when performing equivalent cooling
      experiments no such anomaly is observed. Furthermore, it is elaborated whether
      flux experiments give rise to configurations with lower energies as compared to
      cooling experiments. These results are related to recent experiments by the
      Ediger group where very stable configurations of glass-forming systems have been
      generated via flux experiments.

PMID- 23556744
TI  - Interaction of magnetic transition metal dimers with spin-polarized hydrogenated
      graphene.
AB  - The coadsorption of hydrogen and transition metal dimers Fe2, Co2, Ni2, and FeCo
      on graphene is investigated using density functional theory calculations. Our
      work is motivated by observations that the magnetic moments of these transition
      metal dimers are large and that hydrogen adsorption partitions the graphene
      lattice into magnetic subdomains. Thus, we expect the magnetic dimers to interact
      strongly with the lattice. Our results show that the majority-spin direction of
      the lattice electronic states depends upon the dimer identity, the lattice spin
      polarization being in the same direction as the dimer spin polarization for Fe2
      and FeCo, but opposite for Co2 and Ni2. We can understand this by examining the
      electronic density of states of the dimer and the lattice. We also show that
      coadsorption significantly increases the adsorption energies of both dimer and
      hydrogen leading to a more strongly-adsorbed dimer, while the bond length and
      magnetic moment of the upper dimer atom, the latter important for potential
      magnetic storage applications, are negligibly changed. Our work shows that the
      coadsorbed hydrogen and metal dimer interact over a long-range, this interaction
      being mediated by the hydrogen-induced spin-polarization of the graphene lattice.
      We obtain general insight into how the elemental identity of these magnetic
      dimers determines the spin-polarized states on the hydrogenated graphene lattice.
      These results could be important for potential applications of magnetic
      properties of decorated graphene lattices.

PMID- 23556745
TI  - Perturbation theory for non-spherical fluids based on discretization of the
      interactions.
AB  - An extension of the discrete perturbation theory [A. L. Benavides and A. Gil
      Villegas, Mol. Phys. 97(12), 1225 (1999)] accounting for non-spherical
      interactions is presented. An analytical expression for the Helmholtz free energy
      for an equivalent discrete potential is given as a function of density,
      temperature, and intermolecular parameters with implicit shape dependence. The
      presented procedure is suitable for the description of the thermodynamics of
      general intermolecular potential models of arbitrary shape. The overlap and
      dispersion forces are represented by a discrete potential formed by a sequence of
      square-well and square-shoulders potentials of shape-dependent widths. By varying
      the intermolecular parameters through their geometrical dependence, some
      illustrative cases of square-well spherocylinders and Kihara fluids are
      considered, and their vapor-liquid phase diagrams are tested against available
      simulation data. It is found that this theoretical approach is able to reproduce
      qualitatively and quantitatively well the Monte Carlo data for the selected
      potentials, except near the critical region.

PMID- 23556746
TI  - Comparing different coarse-grained potentials for star polymers.
AB  - We compare different coarse-grained single-blob models for star polymers. We find
      that phenomenological models inspired by the Daoud-Cotton theory reproduce quite
      poorly the thermodynamics of these systems, even if the potential is assumed to
      be density dependent, as done in the analysis of experimental results. Using the
      numerically determined coarse-grained potential, we also determine the minimum
      value f(c) of the functionality of the star polymer for which a fluid-solid
      transition occurs. By applying the Hansen-Verlet criterion we find 35 < f(c) ?
      40. This result is confirmed by an analysis that uses the modified (reference)
      hypernetted chain method and is qualitatively consistent with previous work.

PMID- 23556747
TI  - Method of evaluating curvature-dependent elastic parameters for small unilamellar
      vesicles using molecular dynamics trajectory.
AB  - A numerical method is proposed for evaluating the curvature dependency of elastic
      parameters of a spherical vesicle based on a calculation of the pressure profile
      across the membrane. The proposed method is particularly useful for small
      unilamellar vesicles (SUVs), in which the internal structure of the membrane is
      asymmetric owing to the high curvature. In this case, the elastic energy is
      insufficiently described as a perturbation from a planar membrane. The calculated
      saddle-splay curvature modulus of SUVs, which is about 16 nm in diameter, is
      found to be much higher than that of a planar membrane. A comparison of the free
      energy change in the initial stage of vesicle-to-bicelle transformation with the
      Fromherz theory demonstrates that the elastic parameters estimated for SUVs
      provide better estimation of the free energy than those estimated for a planar
      membrane.

PMID- 23556748
TI  - Capacitance and optical studies of elastic and dielectric properties in an
      organosiloxane tetrapode exhibiting a N(B) phase.
AB  - Biaxial (N(B)) and uniaxial nematic (N(U)) phase behavior was detected and
      confirmed for an organosiloxane tetrapode material using capacitance and
      birefringence measurements. Elastic constants, permittivities at two distinct low
      frequencies, and birefringencies were determined as a function of temperature
      over both the N(U) and the N(B) phase ranges. The N(U)-N(B) transition is clearly
      observed in the birefringencies and conoscopy data. A temperature dependent cross
      over frequency is also detected in this material for the permittivities, allowing
      the electrical switching of both planar and homeotropic aligned samples.

PMID- 23556749
TI  - Near-IR laser generation of a high-energy conformer of L-alanine and the
      mechanism of its decay in a low-temperature nitrogen matrix.
AB  - Monomers of L-alanine (ALA) were isolated in cryogenic nitrogen matrices at 14 K.
      Two conformers were identified for the compound trapped from the gas-phase into
      the solid nitrogen environment. The potential energy surface (PES) of ALA was
      theoretically calculated at the MP2 and QCISD levels. Twelve minima were located
      on this PES. Seven low-energy conformers fall within the 0-10 kJ mol(-1) range
      and should be appreciably populated in the equilibrium gas phase prior to
      deposition. Observation of only two forms in the matrices is explained in terms
      of calculated barriers to conformational rearrangements. All conformers with the
      O=C-O-H moiety in the cis orientation are separated by low barriers and collapse
      to the most stable form I during deposition of the matrix onto the low
      temperature substrate. The second observed form II has the O=C-O-H group in the
      trans orientation. The remaining trans forms have very high relative energies
      (between 24 and 30 kJ mol(-1)) and are not populated. The high-energy trans form
      VI, that differs from I only by rotation of the OH group, was found to be
      separated from other conformers by barriers that are high enough to open a
      perspective for its stabilization in a matrix. The form VI was photoproduced in
      situ by narrow-band near-infrared irradiation of the samples at 6935-6910 cm(-1),
      where the first overtone of the OH stretching vibration in form I appears. The
      photogenerated form VI decays in N2 matrices back to conformer I with a
      characteristic decay time of ~15 min. The mechanism of the VI -> I relaxation is
      rationalized in terms of the proton tunneling.

PMID- 23556750
TI  - Preface: Special topic on the glass transition.
AB  - This Special Topic on the Glass Transition contains a perspective article and a
      collection of original research articles that showcase recent experimental and
      theoretical advances in the field. This special issue provides a timely
      discussion of modern developments in our understanding of the behavior of
      supercooled liquids and amorphous materials, which have implications in diverse
      fields ranging from biology to materials science.

PMID- 23556751
TI  - Perspective: The glass transition.
AB  - We provide here a brief perspective on the glass transition field. It is an
      assessment, written from the point of view of theory, of where the field is and
      where it seems to be heading. We first give an overview of the main
      phenomenological characteristics, or "stylised facts," of the glass transition
      problem, i.e., the central observations that a theory of the physics of glass
      formation should aim to explain in a unified manner. We describe recent
      developments, with a particular focus on real space properties, including
      dynamical heterogeneity and facilitation, the search for underlying spatial or
      structural correlations, and the relation between the thermal glass transition
      and athermal jamming. We then discuss briefly how competing theories of the glass
      transition have adapted and evolved to account for such real space issues. We
      consider in detail two conceptual and methodological approaches put forward
      recently, that aim to access the fundamental critical phenomenon underlying the
      glass transition, be it thermodynamic or dynamic in origin, by means of biasing
      of ensembles, of configurations in the thermodynamic case, or of trajectories in
      the dynamic case. We end with a short outlook.

PMID- 23556753
TI  - Are polar liquids less simple?
AB  - Strong correlation between equilibrium fluctuations under isochoric conditions of
      the potential energy, U, and the virial, W, is a characteristic of liquids that
      implies the presence of certain dynamic properties, such as density scaling of
      the relaxation times and isochronal superpositioning of the relaxation function.
      In this work we employ molecular dynamics simulations on methanol and two
      variations, lacking hydrogen bonds and a dipole moment, to assess the connection
      between the correlation of U and W and these dynamic properties. We show, in
      accord with prior results of others [T. S. Ingebrigtsen, T. B. Schroder, and J.
      C. Dyre, Phys. Rev. X 2, 011011 (2012)], that simple van der Waals liquids
      exhibit both strong correlations and the expected dynamic behavior. However, for
      polar liquids this correspondence breaks down--weaker correlation between U and W
      is not associated with worse conformance to density scaling or isochronal
      superpositioning. The reason for this is that strong correlation between U and W
      only requires their proportionality, whereas the expected dynamic behavior
      depends primarily on constancy of the proportionality constant for all state
      points. For hydrogen-bonded liquids, neither strong correlation nor adherence to
      the dynamic properties is observed; however, this nonconformance is not directly
      related to the concentration of hydrogen bonds, but rather to the greater
      deviation of the intermolecular potential from an inverse power law (IPL). Only
      (hypothetical) liquids having interactions governed strictly by an IPL are
      perfectly correlating and exhibit the consequent dynamic properties over all
      thermodynamic conditions.

PMID- 23556752
TI  - Are the dynamics of a glass embedded in its elastic properties?
AB  - The low temperature dynamics of glass are critically important for many high-tech
      applications. According to the elastic theory of the glass transition, the
      dynamics of glass are controlled by the evolution of shear modulus. In
      particular, the elastic shoving model expresses dynamics in terms of an
      activation energy required to shove aside the surrounding atoms. Here, we present
      a thorough test of the shoving model for predicting the low temperature dynamics
      of an oxide glass system. We show that the nonequilibrium viscosity of glass is
      governed by additional factors beyond changes in shear modulus.

PMID- 23556754
TI  - Glass transition of poly(ethylmethacrylate) admixed and bound to nanoparticles.
AB  - The chain dynamics at the glass transition of poly(ethylmethacrylate) in the bulk
      is compared to that of mixtures of the polymer with nanoparticles by advanced NMR
      methods. In order to make the two components compatible, the particles were
      functionalized with the polymer itself. Particular emphasis is placed on the
      extended local chain conformations of this polymer accessible by (13)C NMR
      spectroscopy. The isotropization dynamics of these extended conformations is only
      slightly changed in the mixtures, but is significantly slowed down by attachment
      of the chains to the nanoparticles themselves. The slowing down is studied at
      various distances from the nanoparticle and is observed for most of the attached
      chains segments except for the chain ends. The results are put into perspective
      to the glass transition in polymers attached to surfaces, thin polymer layers,
      and the chain dynamics of star polymers.

PMID- 23556755
TI  - Modeling the relaxation of polymer glasses under shear and elongational loads.
AB  - Glassy polymers show "strain hardening": at constant extensional load, their flow
      first accelerates, then arrests. Recent experiments under such loading have found
      this to be accompanied by a striking dip in the segmental relaxation time. This
      can be explained by a minimal nonfactorable model combining flow-induced melting
      of a glass with the buildup of stress carried by strained polymers. Within this
      model, liquefaction of segmental motion permits strong flow that creates polymer
      borne stress, slowing the deformation enough for the segmental (or solvent) modes
      then to re-vitrify. Here, we present new results for the corresponding behavior
      under step-stress shear loading, to which very similar physics applies. To
      explain the unloading behavior in the extensional case requires introduction of a
      "crinkle factor" describing a rapid loss of segmental ordering. We discuss in
      more detail here the physics of this, which we argue involves non-entropic
      contributions to the polymer stress, and which might lead to some important
      differences between shear and elongation. We also discuss some fundamental and
      possibly testable issues concerning the physical meaning of entropic elasticity
      in vitrified polymers. Finally, we present new results for the startup of steady
      shear flow, addressing the possible role of transient shear banding.

PMID- 23556756
TI  - Higher-order correlation functions and nonlinear response functions in a gaussian
      trap model.
AB  - The four-time correlation function of a general dynamical variable obeying
      gaussian statistics is calculated for the trap model with a gaussian density of
      states. It is argued that for energy-independent variables this function is
      reminiscent of the four-time functions that have been discussed earlier in the
      interpretation of the results of four-dimensional NMR experiments on supercooled
      liquids. Using an approximative relation between the four-time correlation
      function and the cubic response function the nonlinear susceptibility is
      calculated and the results are compared with the corresponding ones resulting
      from an exact calculation. It is found that the results of the approximation
      change the qualitative behavior of the modulus of the susceptibility. Whereas in
      the exact calculation a peak is found in the modulus in most cases, depending on
      temperature and the additional model parameters no such peak occurs in the
      approximation. This difference has its origin mainly in an incorrect estimate of
      the static response. The results are discussed in relation to recent experimental
      findings.

PMID- 23556757
TI  - Multiple length and time scales of dynamic heterogeneities in model glass-forming
      liquids: a systematic analysis of multi-point and multi-time correlations.
AB  - We report an extensive and systematic investigation of the multi-point and multi
      time correlation functions to reveal the spatio-temporal structures of dynamic
      heterogeneities in glass-forming liquids. Molecular dynamics simulations are
      carried out for the supercooled states of various prototype models of glass
      forming liquids such as binary Kob-Andersen, Wahnstrom, soft-sphere, and network
      forming liquids. While the first three models act as fragile liquids exhibiting
      super-Arrhenius temperature dependence in their relaxation times, the last is a
      strong glass-former exhibiting Arrhenius behavior. First, we quantify the length
      scale of the dynamic heterogeneities utilizing the four-point correlation
      function. The growth of the dynamic length scale with decreasing temperature is
      characterized by various scaling relations that are analogous to the critical
      phenomena. We also examine how the growth of the length scale depends upon the
      model employed. Second, the four-point correlation function is extended to a
      three-time correlation function to characterize the temporal structures of the
      dynamic heterogeneities based on our previous studies [K. Kim and S. Saito, Phys.
      Rev. E 79, 060501(R) (2009); and J. Chem. Phys. 133, 044511 (2010)]. We provide
      comprehensive numerical results obtained from the three-time correlation function
      for the above models. From these calculations, we examine the time scale of the
      dynamic heterogeneities and determine the associated lifetime in a consistent and
      systematic way. Our results indicate that the lifetime of the dynamical
      heterogeneities becomes much longer than the alpha-relaxation time determined
      from a two-point correlation function in fragile liquids. The decoupling between
      the two time scales is remarkable, particularly in supercooled states, and the
      time scales differ by more than an order of magnitude in a more fragile liquid.
      In contrast, the lifetime is shorter than the alpha-relaxation time in
      tetrahedral network-forming strong liquid, even at lower temperatures.

PMID- 23556758
TI  - Dynamic criticality at the jamming transition.
AB  - We characterize vibrational motion occurring at low temperatures in dense
      suspensions of soft repulsive spheres over a broad range of volume fractions
      encompassing the jamming transition at (T = 0, phi = phiJ). We find that
      characteristic time and length scales of thermal vibrations obey critical scaling
      in the vicinity of the jamming transition. We show in particular that the
      amplitude and the time scale of dynamic fluctuations diverge symmetrically on
      both sides of the transition, and directly reveal a diverging correlation length.
      The critical region near phiJ is divided in three different regimes separated by
      a characteristic temperature scale T(?)(phi) that vanishes quadratically with the
      distance to phiJ. While two of them, (T < T(?)(phi), phi > phiJ) and (T <
      T(?)(phi), phi < phiJ), are described by harmonic theories developed in the zero
      temperature limit, the third one for T > T(?)(phi) is inherently anharmonic and
      displays new critical properties. We find that the quadratic scaling of T(?)(phi)
      is due to nonperturbative anharmonic contributions, its amplitude being orders of
      magnitude smaller than the perturbative prediction based on the expansion to
      quartic order in the interactions. Our results show that thermal vibrations in
      colloidal assemblies directly reveal the critical nature of the jamming
      transition. The critical region, however, is very narrow and has not yet been
      attained experimentally, even in recent specifically-dedicated experiments.

PMID- 23556759
TI  - Nonequilibrium static growing length scales in supercooled liquids on approaching
      the glass transition.
AB  - The small wavenumber k behavior of the structure factor S(k) of overcompressed
      amorphous hard-sphere configurations was previously studied for a wide range of
      densities up to the maximally random jammed state, which can be viewed as a
      prototypical glassy state [A. Hopkins, F. H. Stillinger, and S. Torquato, Phys.
      Rev. E 86, 021505 (2012)]. It was found that a precursor to the glassy jammed
      state was evident long before the jamming density was reached as measured by a
      growing nonequilibrium length scale extracted from the volume integral of the
      direct correlation function c(r), which becomes long-ranged as the critical
      jammed state is reached. The present study extends that work by investigating via
      computer simulations two different atomic models: the single-component Z2
      Dzugutov potential in three dimensions and the binary-mixture Kob-Andersen
      potential in two dimensions. Consistent with the aforementioned hard-sphere
      study, we demonstrate that for both models a signature of the glass transition is
      apparent well before the transition temperature is reached as measured by the
      length scale determined from the volume integral of the direct correlation
      function in the single-component case and a generalized direct correlation
      function in the binary-mixture case. The latter quantity is obtained from a
      generalized Ornstein-Zernike integral equation for a certain decoration of the
      atomic point configuration. We also show that these growing length scales, which
      are a consequence of the long-range nature of the direct correlation functions,
      are intrinsically nonequilibrium in nature as determined by an index X that is a
      measure of the deviation from thermal equilibrium. It is also demonstrated that
      this nonequilibrium index, which increases upon supercooling, is correlated with
      a characteristic relaxation time scale.

PMID- 23556760
TI  - Static correlations functions and domain walls in glass-forming liquids: the case
      of a sandwich geometry.
AB  - The problem of measuring nontrivial static correlations in deeply supercooled
      liquids made recently some progress thanks to the introduction of amorphous
      boundary conditions, in which a set of free particles is subject to the effect of
      a different set of particles frozen into their (low temperature) equilibrium
      positions. In this way, one can study the crossover from nonergodic to ergodic
      phase, as the size of the free region grows and the effect of the confinement
      fades. Such crossover defines the so-called point-to-set correlation length,
      which has been measured in a spherical geometry, or cavity. Here, we make further
      progress in the study of correlations under amorphous boundary conditions by
      analyzing the equilibrium properties of a glass-forming liquid, confined in a
      planar ("sandwich") geometry. The mobile particles are subject to amorphous
      boundary conditions with the particles in the surrounding walls frozen into their
      low temperature equilibrium configurations. Compared to the cavity, the sandwich
      geometry has three main advantages: (i) the width of the sandwich is decoupled
      from its longitudinal size, making the thermodynamic limit possible; (ii) for
      very large width, the behaviour off a single wall can be studied; (iii) we can
      use "anti-parallel" boundary conditions to force a domain wall and measure its
      excess energy. Our results confirm that amorphous boundary conditions are indeed
      a very useful new tool in the study of static properties of glass-forming
      liquids, but also raise some warning about the fact that not all correlation
      functions that can be calculated in this framework give the same qualitative
      results.

PMID- 23556761
TI  - Evolution of the dynamic susceptibility in molecular glass formers: results from
      light scattering, dielectric spectroscopy, and NMR.
AB  - Although broadly studied, molecular glass formers are not well investigated above
      their melting point. Correlation times down to 10(-12) s are easily accessible
      when studying low-T(g) systems by depolarized light scattering, employing a
      tandem-Fabry-Perot interferometer and a double monochromator. When combining
      these techniques with state-of-the-art photon correlation spectroscopy (PCS),
      broad band susceptibility spectra become accessible which can compete with those
      of dielectric spectroscopy (DS). Comparing the results with those from DS,
      optical Kerr effect, and NMR, we describe the evolution of the susceptibilities
      starting from the boiling point T(b) down to T(g), i.e., from simple liquid to
      glassy dynamics. Special attention is given to the emergence of the excess wing
      contribution which is also probed by PCS and which signals a crossover of the
      spectral evolution. The process is attributed to a small-angle precursor process
      of the alpha-relaxation, and the apparent probe dependent stretching of the alpha
      process is explained by a probe dependent contribution of the excess wing. Upon
      cooling, its emergence is linked to a strong decrease of the strength of the fast
      dynamics which is taken as reorientational analog of the anomaly of the Debye
      Waller factor. Many glass formers show in addition a slow beta-process which
      manifests itself rather universally in NMR, in DS, however, with different
      amplitudes, but not at all in PCS experiments. Finally, a three-parameter
      function is discussed interpolating tau(alpha)(T) from T(b) to T(g) by connecting
      high- and low-temperature dynamics.

PMID- 23556762
TI  - Non-exponential nature of calorimetric and other relaxations: effects of 2 nm
      size solutes, loss of translational diffusion, isomer specificity, and sample
      size.
AB  - Certain distributions of relaxation times can be described in terms of a non
      exponential response parameter, beta, of value between 0 and 1. Both beta and the
      relaxation time, tau0, of a material depend upon the probe used for studying its
      dynamics and the value of beta is qualitatively related to the non-Arrhenius
      variation of viscosity and tau0. A solute adds to the diversity of an
      intermolecular environment and is therefore expected to reduce beta, i.e., to
      increase the distribution and to change tau0. We argue that the calorimetric
      value beta(cal) determined from the specific heat [Cp = T(dS/dT)p] data is a more
      appropriate measure of the distribution of relaxation times arising from
      configurational fluctuations than beta determined from other properties, and
      report a study of beta(cal) of two sets of binary mixtures, each containing a
      different molecule of ~2 nm size. We find that beta(cal) changes monotonically
      with the composition, i.e., solute molecules modify the nano-scale composition
      and may increase or decrease tau0, but do not always decrease beta(cal). (Plots
      of beta(cal) against the composition do not show a minimum.) We also analyze the
      data from the literature, and find that (i) beta(cal) of an orientationally
      disordered crystal is less than that of its liquid, (ii) beta(cal) varies with
      the isomer's nature, and chiral centers in a molecule decrease beta(cal), and
      (iii) beta(cal) decreases when a sample's thickness is decreased to the nm-scale.
      After examining the difference between beta(cal) and beta determined from other
      properties we discuss the consequences of our findings for theories of non
      exponential response, and suggest that studies of beta(cal) may be more revealing
      of structure-freezing than studies of the non-Arrhenius behavior. On the basis of
      previous reports that beta -> 1 for dielectric relaxation of liquids of
      centiPoise viscosity observed at GHz frequencies, we argue that its molecular
      mechanism is the same as that of the Johari-Goldstein (JG) relaxation. Its
      spectrum becomes broader on cooling and its unimodal distribution reversibly
      changes to a bimodal distribution, each of beta < 1. Kinetic freezing of the
      slower modes of the bimodal distribution produces a glass. After this
      bifurcation, the faster, original relaxation persists as a weak JG relaxation at
      T -> T(g), and in the glassy state.

PMID- 23556763
TI  - Nonlinear active micro-rheology in a glass-forming soft-sphere mixture.
AB  - We present extensive molecular dynamics computer simulations of a glass-forming
      Yukawa mixture, investigating the nonlinear response of a single particle that is
      pulled through the system by a constant force. Structural changes around the
      pulled particle are analyzed by pair correlation functions, measured in the
      deeply supercooled state of the system. A regime of intermediate force strengths
      is found where the structural changes around the pulled particle are small,
      although its steady-state velocity shows a strong nonlinear response. This
      nonlinear response regime is characterized by a force-temperature superposition
      principle of a Peclet number and anisotropic diffusive behavior. In the direction
      parallel to the force, mean-square displacements show anomalous superdiffusion in
      the long time limit. We analyze this superdiffusive behavior by means of the van
      Hove correlation function of the pulled particle. Perpendicular to the force, the
      driven particle shows diffusive behavior for all considered force strengths and
      temperatures. We discuss the dynamics perpendicular and parallel to the force in
      terms of effective temperatures.

PMID- 23556764
TI  - On the Bauschinger effect in supercooled melts under shear: results from mode
      coupling theory and molecular dynamics simulations.
AB  - We study the nonlinear rheology of a glass-forming binary mixture under the
      reversal of shear flow using molecular dynamics simulations and a schematic model
      of the mode-coupling theory of the glass transition (MCT). Memory effects lead to
      a history-dependent response, as exemplified by the vanishing of a stress
      overshoot phenomenon in the stress-strain curves of the sheared liquid, and a
      change in the apparent elastic coefficients around states with zero stress. We
      investigate the various retarded contributions to the stress response at a given
      time schematically within MCT. The connection of this macroscopic response to
      single-particle motion is demonstrated using molecular-dynamics simulation.

PMID- 23556765
TI  - Dynamics of thermal vibrational motions and stringlike jump motions in three
      dimensional glass-forming liquids.
AB  - Using molecular dynamics simulation on a glass-forming liquid in three
      dimensions, we investigate the thermal vibrational motions, the configuration
      changes caused by stringlike jump motions, and their close correlations. The
      heterogeneous vibrational motions are visualized in terms of a vibration length
      Si(t) defined for each particle i. The structure factor for the inhomogeneity of
      Si(t)(2) is also calculated, which exhibits considerable long wavelength
      enhancement. By examining the birth times of strings, they are shown to appear
      collectively and intermittently. We show that particles with larger Si(t) tend to
      trigger jump motions more frequently at later times than those with smaller
      Si(t). We also show that the particles with fewer bonds tend to have larger Si(t)
      and participate more frequently in the stringlike motions.

PMID- 23556766
TI  - Geometrical frustration and static correlations in hard-sphere glass formers.
AB  - We analytically and numerically characterize the structure of hard-sphere fluids
      in order to review various geometrical frustration scenarios of the glass
      transition. We find generalized polytetrahedral order to be correlated with
      increasing fluid packing fraction, but to become increasingly irrelevant with
      increasing dimension. We also find the growth in structural correlations to be
      modest in the dynamical regime accessible to computer simulations.

PMID- 23556767
TI  - Can a stable glass be superheated? Modelling the kinetic stability of coated
      glassy films.
AB  - The fabrication of ultra-stable glass films by vapour deposition and their
      subsequent front-like response to annealing are both manifestations of the
      enhancement of dynamics at the amorphous surface. We use the facilitated kinetic
      Ising model to model the behaviour of ultra-stable amorphous films when a coating
      is applied that suppresses the dynamics at the film surface. The consequences of
      this manipulation of the film include glass films that can be heated to
      temperatures in excess of the glass transition without transforming into the
      liquid, the possibility of direct visualization of the spatial distribution of
      intrinsic dynamic heterogeneities, and the possibility of using surface treatment
      to engineer relaxation of these glass films.

PMID- 23556768
TI  - Manipulating the properties of stable organic glasses using kinetic facilitation.
AB  - In contrast to ordinary glasses, when highly stable organic glasses are annealed
      at temperatures above T(g), they transform heterogeneously into the liquid state
      by a constant velocity propagating front that initiates at the free surface. The
      evolution of this growth front has been interpreted as kinetic facilitation,
      i.e., efficiently packed molecules become un-jammed only when mobility is
      available in adjacent regions. Here we use physical vapor deposition to prepare
      highly stable glasses of indomethacin in which mobile regions are either added to
      or eliminated from the samples in an attempt to use the kinetic facilitation
      concept to manipulate the properties of these materials. The addition of higher
      mobility layers in the interior of a thin stable glass film or at the substrate
      surface is shown to initiate new growth fronts, thus demonstrating that kinetic
      facilitation occurs independently of free surface mobility. Conversely, capping
      the free surface with a higher T(g) stable glass stops the growth front,
      apparently by eliminating surface mobility, thus increasing sample stability by
      slowing the transformation to the supercooled liquid.

PMID- 23556769
TI  - Microrheology of supercooled liquids in terms of a continuous time random walk.
AB  - Molecular dynamics simulations of a glass-forming model system are performed
      under application of a microrheological perturbation on a tagged particle. The
      trajectory of that particle is studied in its underlying potential energy
      landscape. Discretization of the configuration space is achieved via a metabasin
      analysis. The linear and nonlinear responses of drift and diffusive behavior can
      be interpreted and analyzed in terms of a continuous time random walk. In this
      way, the physical origin of linear and nonlinear response can be identified.
      Critical forces are determined and compared with predictions from literature.

PMID- 23556770
TI  - Dynamics of glass-forming liquids. XVI. Observation of ultrastable glass
      transformation via dielectric spectroscopy.
AB  - The transformation of vapor-deposited ultrastable glasses of indomethacin (IMC)
      into the supercooled liquid state near T(g) is monitored by means of dielectric
      spectroscopy. Films with thickness between 400 and 800 nm are deposited on
      differential interdigitated electrode cells and their loss profiles are measured
      during isothermal annealing using a dual-channel impedance technique for
      frequencies between 0.03 and 100 Hz. All dielectric loss spectra observed during
      the transformation process can be explained by a volume fraction of the
      supercooled liquid that increases linearly with time. From the early stages of
      the transformation to the liquid that is formed via complete annealing of the
      ultrastable glass, the average dielectric relaxation time as well as the
      distribution of relaxation times of the liquid component are identical to those
      of the conventional liquid obtained by cooling the melt. The dependence of the
      transformation rate on the film thickness is consistent with a growth front
      mechanism for the direct conversion from the ultrastable glass to the equilibrium
      supercooled liquid. We conclude that the IMC liquid recovered from the
      ultrastable glass is structurally and dynamically identical to the conventional
      supercooled state.

PMID- 23556771
TI  - Local elastic response measured near the colloidal glass transition.
AB  - We examine the response of a dense colloidal suspension to a local force applied
      by a small magnetic bead. For small forces, we find a linear relationship between
      the force and the displacement, suggesting the medium is elastic, even though our
      colloidal samples macroscopically behave as fluids. We interpret this as a
      measure of the strength of colloidal caging, reflecting the proximity of the
      samples' volume fractions to the colloidal glass transition. The strain field of
      the colloidal particles surrounding the magnetic probe appears similar to that of
      an isotropic homogeneous elastic medium. When the applied force is removed, the
      strain relaxes as a stretched exponential in time. We introduce a model that
      suggests this behavior is due to the diffusive relaxation of strain in the
      colloidal sample.

PMID- 23556772
TI  - Microscopic theory of the glassy dynamics of passive and active network
      materials.
AB  - Signatures of glassy dynamics have been identified experimentally for a rich
      variety of materials in which molecular networks provide rigidity. Here we
      present a theoretical framework to study the glassy behavior of both passive and
      active network materials. We construct a general microscopic network model that
      incorporates nonlinear elasticity of individual filaments and steric constraints
      due to crowding. Based on constructive analogies between structural glass forming
      liquids and random field Ising magnets implemented using a heterogeneous self
      consistent phonon method, our scheme provides a microscopic approach to determine
      the mismatch surface tension and the configurational entropy, which compete in
      determining the barrier for structural rearrangements within the random first
      order transition theory of escape from a local energy minimum. The influence of
      crosslinking on the fragility of inorganic network glass formers is recapitulated
      by the model. For active network materials, the mapping, which correlates the
      glassy characteristics to the network architecture and properties of
      nonequilibrium motor processes, is shown to capture several key experimental
      observations on the cytoskeleton of living cells: Highly connected tense networks
      behave as strong glass formers; intense motor action promotes reconfiguration.
      The fact that our model assuming a negative motor susceptibility predicts the
      latter suggests that on average the motorized processes in living cells do resist
      the imposed mechanical load. Our calculations also identify a spinodal point
      where simultaneously the mismatch penalty vanishes and the mechanical stability
      of amorphous packing disappears.

PMID- 23556773
TI  - Statistics of modifier distributions in mixed network glasses.
AB  - The constituents of any network glass can be broadly classified as either network
      formers or network modifiers. Network formers, such as SiO2, Al2O3, B2O3, P2O5,
      etc., provide the backbone of the glass network and are the primary source of its
      rigid constraints. Network modifiers play a supporting role, such as charge
      stabilization of the network formers or alteration of the network topology
      through rupture of bridging bonds and introduction of floppy modes. The specific
      role of the modifiers depends on which network formers are present in the glass
      and the relative free energies of modifier interactions with each type of network
      former site. This variation of free energy with modifier speciation is
      responsible for the so-called mixed network former effect, i.e., the nonlinear
      scaling of property values in glasses having fixed modifier concentration but a
      varying ratio of network formers. In this paper, a general theoretical framework
      is presented describing the statistical mechanics of modifier speciation in mixed
      network glasses. The model provides a natural explanation for the mixed network
      former effect and also accounts for the impact of thermal history and relaxation
      on glass network topology.

PMID- 23556774
TI  - Dynamic heterogeneities above and below the mode-coupling temperature: evidence
      of a dynamic crossover.
AB  - We examine dynamic heterogeneities in a model glass-forming fluid, a binary
      harmonic sphere mixture, above and below the mode-coupling temperature T(c). We
      calculate the ensemble independent susceptibility chi4(tau(alpha)) and the
      dynamic correlation length xi4(tau(alpha)) at the alpha-relaxation time
      tau(alpha). We also examine in detail the temperature dependence of tau(alpha)
      and the diffusion coefficient D. For higher temperatures, we find that the
      standard Stokes-Einstein relationship, D~tau(alpha)(-1), holds, but at lower
      temperatures a fractional Stokes-Einstein relationship, D~tau(alpha)(-sigma) with
      sigma = 0.65, emerges. By examining the relationships between tau(alpha), D,
      chi4(tau(alpha)), and xi4(tau(alpha)) we determine that the emergence of the
      fractional Stokes-Einstein relationship is accompanied by a dynamic crossover
      from tau(alpha)~e(k2xi4) at higher temperatures to tau(alpha)~e(k1xi4(3/2)) at
      lower temperatures.

PMID- 23556775
TI  - Single molecule probe reports of dynamic heterogeneity in supercooled ortho
      terphenyl.
AB  - The rotational dynamics of three perylene diimide dyes are studied on the single
      molecule (SM) level in ortho-terphenyl (OTP) near the glass transition
      temperature (T(g)). At all temperatures probed, spanning 1.03-1.06 T(g), each of
      the three probes exhibits rotational correlation times, tau(c), that span more
      than a decade, consistent with the presence of spatially heterogeneous dynamics
      in OTP. No trend is found as a function of temperature, but a trend as a function
      of probe is observed: Average probe rotational correlation time scales inversely
      with breadth of SM tau(c) distribution, with faster probes exhibiting broader
      tau(c) distributions. This implies that dynamic exchange occurs on and below time
      scales associated with probe rotation. Extrapolating FWHM of rotational
      relaxation times to the structural relaxation time of the host shows that the
      tau(c) distribution would span nearly two decades in the limit of no probe
      temporal averaging. Comparison with SM measurements in glycerol suggests that OTP
      demonstrates a greater degree of spatially heterogeneous dynamics in this
      temperature range than does glycerol.

PMID- 23556776
TI  - Relationship between neighbor number and vibrational spectra in disordered
      colloidal clusters with attractive interactions.
AB  - We study connections between vibrational spectra and average nearest neighbor
      number in disordered clusters of colloidal particles with attractive
      interactions. Measurements of displacement covariances between particles in each
      cluster permit calculation of the stiffness matrix, which contains effective
      spring constants linking pairs of particles. From the cluster stiffness matrix,
      we derive vibrational properties of corresponding "shadow" glassy clusters, with
      the same geometric configuration and interactions as the "source" cluster but
      without damping. Here, we investigate the stiffness matrix to elucidate the
      origin of the correlations between the median frequency of cluster vibrational
      modes and average number of nearest neighbors in the cluster. We find that the
      mean confining stiffness of particles in a cluster, i.e., the ensemble-averaged
      sum of nearest neighbor spring constants, correlates strongly with average
      nearest neighbor number, and even more strongly with median frequency. Further,
      we find that the average oscillation frequency of an individual particle is set
      by the total stiffness of its nearest neighbor bonds; this average frequency
      increases as the square root of the nearest neighbor bond stiffness, in a manner
      similar to the simple harmonic oscillator.

PMID- 23556777
TI  - Relaxation processes in liquids: variations on a theme by Stokes and Einstein.
AB  - We investigate numerically the temperature and density dependence of the Stokes
      Einstein ratio, Deta/T, and of two commonly-used variants thereof, Dtau and
      Dtau/T, where D is a diffusivity, eta the shear viscosity, and tau a structural
      relaxation time. We consider a family of atomic binary mixtures with
      systematically-softened repulsive interactions, and the Lewis-Wahnstrom model of
      ortho-terphenyl (OTP). The three quantities grow significantly as the temperature
      decreases in the supercooled regime, a well-known phenomenon. At higher
      temperatures, Dtau exhibits negative violations of Stokes-Einstein behavior,
      i.e., decrease upon cooling, for the atomic systems, though not for OTP. We
      consider two choices for the relaxation time, one based on the decay of the self
      intermediate scattering function, and the other on the integral of the stress
      autocorrelation function. The instantaneous shear modulus exhibits appreciable
      temperature dependence for the two classes of systems investigated here. Our
      results suggest that commonly-invoked assumptions, such as tau ~ eta and tau ~
      eta/T, should be critically evaluated across a wide spectrum of systems and
      thermodynamic conditions. We find the Stokes-Einstein ratio, Deta/T, to be
      constant across a broad range of temperatures and densities for the two classes
      of systems investigated here.

PMID- 23556778
TI  - Are rare, long waiting times between rearrangement events responsible for the
      slowdown of the dynamics at the glass transition?
AB  - The dramatic slowdown of the structural relaxation at the glass transition is one
      of the most puzzling features of glass dynamics. Single molecule orientational
      correlation times show this strong Vogel-Fulcher-Tammann temperature dependence
      typical for glasses. Through statistical analysis of single molecule
      trajectories, we can identify individual glass rearrangement events in the
      vicinity of a probe molecule in the glass former poly(vinyl acetate) from 8 K
      below to 6 K above the glass transition temperature. We find that changes in the
      distribution of waiting times between individual glass rearrangement events are
      much less dramatic with temperature, the main difference being a small, but
      decisive number of increasingly long waiting times at lower temperatures. We
      notice similar individual, local relaxation events in molecular dynamics
      trajectories for a variety of glassy systems further from the glass transition,
      leading to waiting time distributions with similar features as those observed in
      the single molecule experiments. We show that these rare long waiting times are
      responsible for the dramatic increase in correlation time upon cooling.

PMID- 23556779
TI  - Evolution of collective motion in a model glass-forming liquid during physical
      aging.
AB  - At temperatures moderately below their glass transition temperature, the
      properties of many glass-forming materials can evolve slowly with time in a
      process known as physical aging whereby the thermodynamic, mechanical, and
      dynamic properties all drift towards their equilibrium values. In this work, we
      study the evolution of the thermodynamic and dynamic properties during physical
      aging for a model polymer glass. Specifically, we test the relationship between
      an estimate of the size of the cooperative rearrangements taking the form of
      strings and the effective structural relaxation time predicted by the Adam-Gibbs
      relationship for both an equilibrium supercooled liquid and the same fluid
      undergoing physical aging towards equilibrium after a series of temperature
      jumps. We find that there is apparently a close correlation between a structural
      feature of the fluid, the size of the string-like rearrangements, and the
      structural relaxation time, although the relationship for the aging fluid appears
      to be distinct from that of the fluid at equilibrium.

PMID- 23556780
TI  - The first jamming crossover: geometric and mechanical features.
AB  - The jamming transition characterizes athermal systems of particles interacting
      via finite range repulsive potentials, and occurs on increasing the density when
      particles cannot avoid making contacts with those of their first coordination
      shell. We have recently shown [M. Pica Ciamarra and P. Sollich, e-print
      arXiv:1209.3334] that the same systems are also characterized by a series of
      jamming crossovers. These occur at higher volume fractions as particles are
      forced to make contact with those of subsequent coordination shells. At finite
      temperature, the crossovers give rise to dynamic and thermodynamic density
      anomalies, including a diffusivity anomaly and a negative thermal expansion
      coefficient. Density anomalies may therefore be related to structural changes
      occurring at the jamming crossovers. Here we elucidate these structural changes,
      investigating the evolution of the structure and of the mechanical properties of
      a jammed system as its volume fraction varies from the jamming transition to and
      beyond the first jamming crossover. We show that the first jamming crossover
      occurs at a well defined volume fraction, and that it induces a rearrangement of
      the force network causing a softening of the system. It also causes qualitative
      changes in the normal mode density of states and the spatial properties of the
      normal mode vectors.

PMID- 23556781
TI  - Evaluation of heterogeneity measures and their relation to the glass transition.
AB  - For most phase transitions, dynamic slowdown is accompanied by a static structure
      change. However, in the case of the supercooled liquid, which is a special liquid
      state below the melting temperature, one observes pronounced dynamic slowdown,
      i.e., diffusion coefficient, relaxation time, and viscosity change 10-14 orders
      of magnitude within a relatively small temperature range. This occurs without the
      pronounced static structure change observed in other phase transitions. Over the
      past several decades, there has been extensive research aimed to understand why
      the glass transition occurs, to establish what the glass transition exactly is,
      and to improve our understanding of how molecules move near to the glass
      transition. In the present work, we have examined the idea that the dramatic
      reduction in molecular mobility or dynamic slowdown in a supercooled liquid
      during cooling from above T(g) occurs because of the increasing length scale of
      heterogeneous subregions, or the cooperatively rearranging regions (CRR) proposed
      by Adam and Gibbs. Although there is little doubt about the existence of
      microscopic heterogeneous regions, the absence of the "universal" parameters to
      characterize the temperature dependent heterogeneity data and type of temperature
      divergence among different parameters over the same temperature range suggests
      the possibility that the heterogeneity itself may not relate to the CRR directly
      and thus may not be the key cause of the glass transition phenomenon. It remains
      an important research challenge to identify which, if any, of the heterogeneity
      parameters relates in a causal manner to the glass transition.

PMID- 23556782
TI  - Space-time phase transitions in the East model with a softened kinetic
      constraint.
AB  - The East model has a dynamical phase transition between an active (fluid) and
      inactive (glass) state. We show that this phase transition generalizes to
      "softened" systems where constraint violations are allowed with small but finite
      probabilities. Moreover, we show that the first order coexistence line separating
      the active and inactive phases terminates in a finite-temperature space-time
      critical point. Implications of these results for equilibrium dynamics are
      discussed.

PMID- 23556783
TI  - Scaling between relaxation, transport and caged dynamics in a binary mixture on a
      per-component basis.
AB  - The universal scaling between the average slow relaxation/transport and the
      average picosecond rattling motion inside the cage of the first neighbors has
      been evidenced in a variety of numerical simulations and experiments. Here, we
      first show that the scaling does not need information concerning the arbitrarily
      defined glass transition region and relies on a single characteristic length
      scale a(2)(1/2) which is determined even far from that region. This prompts the
      definition of a novel reduced rattling amplitude <u(2)>(1/2) which has been
      investigated by extensive molecular-dynamics simulations addressing the slow
      relaxation, the diffusivity, and the fast cage-dynamics of both components of an
      atomic binary mixture. States with different potential, density, and temperature
      are considered. It is found that if two states exhibit coinciding incoherent van
      Hove function on the picosecond timescale, the coincidence is observed at long
      times too, including the large-distance exponential decay--a signature of
      heterogeneous dynamics--observed when the relaxation is slow. A major result of
      the present study is that the correlation plot between the diffusivity of the two
      components of the binary mixtures and their respective reduced rattling amplitude
      collapse on the same master curve. This holds true also for the structural
      relaxation of the two components and the unique master curve coincides with the
      one of the average scaling. It is shown that the breakdown of the Stokes-Einstein
      law exhibited by the distinct atomic species of the mixture and the monomers of a
      chain in a polymer melt is predicted at the same reduced rattling amplitude.
      Finally, we evidence that the well-known temperature/density thermodynamic
      scaling of the transport and the relaxation of the mixture is still valid on the
      picosecond timescale of the rattling motion inside the cage. This provides a link
      between the fast dynamics and the thermodynamic scaling of the slow dynamics.

PMID- 23556784
TI  - Shear modulus of simulated glass-forming model systems: effects of boundary
      condition, temperature, and sampling time.
AB  - The shear modulus G of two glass-forming colloidal model systems in d = 3 and d =
      2 dimensions is investigated by means of, respectively, molecular dynamics and
      Monte Carlo simulations. Comparing ensembles where either the shear strain gamma
      or the conjugated (mean) shear stress tau are imposed, we compute G from the
      respective stress and strain fluctuations as a function of temperature T while
      keeping a constant normal pressure P. The choice of the ensemble is seen to be
      highly relevant for the shear stress fluctuations MU(F)(T) which at constant tau
      decay monotonously with T following the affine shear elasticity MU(A)(T), i.e., a
      simple two-point correlation function. At variance, non-monotonous behavior with
      a maximum at the glass transition temperature T(g) is demonstrated for MUF(T) at
      constant gamma. The increase of G below T(g) is reasonably fitted for both models
      by a continuous cusp singularity, G(T) ? (1 - T/T(g))(1/2), in qualitative
      agreement with recent theoretical predictions. It is argued, however, that longer
      sampling times may lead to a sharper transition.

PMID- 23556785
TI  - Microscopic calculation of the free energy cost for activated transport in glass
      forming liquids.
AB  - Activated transport in liquids--supercooled liquids in particular--occurs via
      mutual nucleation of alternative, aperiodic minima of the free energy. Xia and
      Wolynes [Proc. Natl. Acad. Sci. U.S.A. 97, 2990 (2000)] have made a general
      argument that at temperatures near the ideal glass transition, the surface
      penalty for this kind of nucleation is largely determined by the temperature and
      the logarithm of the size of the vibrational fluctuation of rigid molecular units
      about the local minimum. Here, we independently show how to estimate this surface
      tension and, hence, the activation barrier for the activated transport for
      several actual liquids, using their structure factors and knowledge of the finite
      frequency elastic constants. In this estimate, the activation free energy, while
      depending on the configurational entropy, also depends on the elastic modulus as
      in the "shoving" models. The resulting estimates are however consistent with the
      estimate provided by Xia and Wolynes' argument near the glass transition and, in
      addition, reflect the barrier softening effects predicted earlier for fragile
      substances.

PMID- 23556786
TI  - Identification of long-lived clusters and their link to slow dynamics in a model
      glass former.
AB  - We study the relationship between local structural ordering and dynamical
      heterogeneities in a model glass-forming liquid, the Wahnstrom mixture. A novel
      cluster-based approach is used to detect local energy minimum polyhedral clusters
      and local crystalline environments. A structure-specific time correlation
      function is then devised to determine their temporal stability. For our system,
      the lifetime correlation function for icosahedral clusters decays far slower than
      for those of similarly sized but topologically distinct clusters. Upon cooling,
      the icosahedra form domains of increasing size and their lifetime increases with
      the size of the domains. Furthermore, these long-lived domains lower the mobility
      of neighboring particles. These structured domains show correlations with the
      slow regions of the dynamical heterogeneities that form on cooling towards the
      glass transition. Although icosahedral clusters with a particular composition and
      arrangement of large and small particles are structural elements of the crystal,
      we find that most icosahedral clusters lack such order in composition and
      arrangement and thus local crystalline ordering makes only a limited contribution
      to this process. Finally, we characterize the spatial correlation of the domains
      of icosahedra by two structural correlation lengths and compare them with the
      four-point dynamic correlation length. All the length scales increase upon
      cooling, but in different ways.

PMID- 23556787
TI  - Importance of many-body correlations in glass transition: an example from
      polydisperse hard spheres.
AB  - Most of the liquid-state theories, including glass-transition theories, are
      constructed on the basis of two-body density correlations. However, we have
      recently shown that many-body correlations, in particular, bond orientational
      correlations, play a key role in both the glass transition and the
      crystallization transition. Here we show, with numerical simulations of
      supercooled polydisperse hard spheres systems, that the length-scale associated
      with any two-point spatial correlation function does not increase toward the
      glass transition. A growing length-scale is instead revealed by considering many
      body correlation functions, such as correlators of orientational order, which
      follows the length-scale of the dynamic heterogeneities. Despite the growing of
      crystal-like bond orientational order, we reveal that the stability against
      crystallization with increasing polydispersity is due to an increasing population
      of icosahedral arrangements of particles. Our results suggest that, for this type
      of systems, many-body correlations are a manifestation of the link between the
      vitrification and the crystallization phenomena. Whether a system is vitrified or
      crystallized can be controlled by the degree of frustration against
      crystallization, polydispersity in this case.

PMID- 23556788
TI  - A small subset of normal modes mimics the properties of dynamical heterogeneity
      in a model supercooled liquid.
AB  - In this work, we study the nature of transitions between inherent structures of a
      two-dimensional model supercooled liquid. We demonstrate that these transitions
      occur predominately along a small number of directions on the energy landscape.
      Moreover, we show that the number of such directions decreases as the temperature
      of the liquid is decreased in the mildly supercooled regime, in concert with
      earlier studies on an athermal jamming system. We show that this decrease happens
      in parallel with a change in character of the transitions as dynamics in the
      system become more heterogeneous and localized. We investigate the origin of
      these trends, which suggests interesting connections between jamming and thermal
      glassy phenomena.

PMID- 23556790
TI  - Static triplet correlations in glass-forming liquids: a molecular dynamics study.
AB  - We present a numerical evaluation of the three-point static correlations
      functions of the Kob-Andersen Lennard-Jones binary mixture and of its purely
      repulsive, Weeks-Chandler-Andersen variant. In the glassy regime, the two models
      possess a similar pair structure, yet their dynamics differ markedly. The static
      triplet correlation functions S(3) indicate that the local ordering is more
      pronounced in the Lennard-Jones model, an observation consistent with its slower
      dynamics. A comparison of the direct triplet correlation functions c(3) reveals
      that these structural differences are due, to a good extent, to an amplification
      of the small discrepancies observed at the pair level. We demonstrate the
      existence of a broad, positive peak at small wave-vectors and angles in c(3). In
      this portion of k-space, slight, systematic differences between the models are
      observed, revealing "genuine" three-body contributions to the triplet structure.
      The possible role of the low-k features of c(3) and the implications of our
      results for dynamic theories of the glass transition are discussed.

PMID- 23556789
TI  - String-like cooperative motion in homogeneous melting.
AB  - Despite the fundamental nature and practical importance of melting, there is
      still no generally accepted theory of this ubiquitous phenomenon. Even the
      earliest simulations of melting of hard discs by Alder and Wainwright indicated
      the active role of collective atomic motion in melting and here we utilize
      molecular dynamics simulation to determine whether these correlated motions are
      similar to those found in recent studies of glass-forming (GF) liquids and other
      condensed, strongly interacting, particle systems. We indeed find string-like
      collective atomic motion in our simulations of "superheated" Ni crystals, but
      other observations indicate significant differences from GF liquids. For example,
      we observe neither stretched exponential structural relaxation, nor any
      decoupling phenomenon, while we do find a boson peak, findings that have strong
      implications for understanding the physical origin of these universal properties
      of GF liquids. Our simulations also provide a novel view of "homogeneous" melting
      in which a small concentration of interstitial defects exerts a powerful effect
      on the crystal stability through their initiation and propagation of collective
      atomic motion. These relatively rare point defects are found to propagate down
      the strings like solitons, driving the collective motion. Crystal integrity
      remains preserved when the permutational atomic motions take the form of ring
      like atomic exchanges, but a topological transition occurs at higher temperatures
      where the rings open to form linear chains similar in geometrical form and length
      distribution to the strings of GF liquids. The local symmetry breaking effect of
      the open strings apparently destabilizes the local lattice structure and
      precipitates crystal melting. The crystal defects are thus not static entities
      under dynamic conditions, such as elevated temperatures or material loading, but
      rather are active agents exhibiting a rich nonlinear dynamics that is not
      addressed in conventional "static" defect melting models.

PMID- 23556791
TI  - Static replica approach to critical correlations in glassy systems.
AB  - We discuss the slow relaxation phenomenon in glassy systems by means of replicas
      by constructing a static field theory approach to the problem. At the mean field
      level we study how criticality in the four point correlation functions arises
      because of the presence of soft modes and we derive an effective replica field
      theory for these critical fluctuations. By using this at the gaussian level we
      obtain many physical quantities: the correlation length, the exponent parameter
      that controls the mode-coupling dynamical exponents for the two-point correlation
      functions, and the prefactor of the critical part of the four point correlation
      functions. Moreover, we perform a one-loop computation in order to identify the
      region in which the mean field gaussian approximation is valid. The result is a
      Ginzburg criterion for the glass transition. We define and compute in this way a
      proper Ginzburg number. Finally, we present numerical values of all these
      quantities obtained from the hypernetted chain approximation for the replicated
      liquid theory.

PMID- 23556793
TI  - Systematic expansion in the order parameter for replica theory of the dynamical
      glass transition.
AB  - It has been shown recently that predictions from mode-coupling theory for the
      glass transition of hard-spheres become increasingly bad when dimensionality
      increases, whereas replica theory predicts a correct scaling. Nevertheless if one
      focuses on the regime around the dynamical transition in three dimensions, mode
      coupling results are far more convincing than replica theory predictions. It
      seems thus necessary to reconcile the two theoretic approaches in order to obtain
      a theory that interpolates between low-dimensional, mode-coupling results, and
      "mean-field" results from replica theory. Even though quantitative results for
      the dynamical transition issued from replica theory are not accurate in low
      dimensions, two different approximation schemes--small cage expansion and
      replicated hyper-netted-chain (RHNC)--provide the correct qualitative picture for
      the transition, namely, a discontinuous jump of a static order parameter from
      zero to a finite value. The purpose of this work is to develop a systematic
      expansion around the RHNC result in powers of the static order parameter, and to
      calculate the first correction in this expansion. Interestingly, this correction
      involves the static three-body correlations of the liquid. More importantly, we
      separately demonstrate that higher order terms in the expansion are
      quantitatively relevant at the transition, and that the usual mode-coupling
      kernel, involving two-body direct correlation functions of the liquid, cannot be
      recovered from static computations.

PMID- 23556792
TI  - The relationship of dynamical heterogeneity to the Adam-Gibbs and random first
      order transition theories of glass formation.
AB  - We carefully examine common measures of dynamical heterogeneity for a model
      polymer melt and test how these scales compare with those hypothesized by the
      Adam and Gibbs (AG) and random first-order transition (RFOT) theories of
      relaxation in glass-forming liquids. To this end, we first analyze clusters of
      highly mobile particles, the string-like collective motion of these mobile
      particles, and clusters of relative low mobility. We show that the time scale of
      the high-mobility clusters and strings is associated with a diffusive time scale,
      while the low-mobility particles' time scale relates to a structural relaxation
      time. The difference of the characteristic times for the high- and low-mobility
      particles naturally explains the well-known decoupling of diffusion and
      structural relaxation time scales. Despite the inherent difference of dynamics
      between high- and low-mobility particles, we find a high degree of similarity in
      the geometrical structure of these particle clusters. In particular, we show that
      the fractal dimensions of these clusters are consistent with those of swollen
      branched polymers or branched polymers with screened excluded-volume
      interactions, corresponding to lattice animals and percolation clusters,
      respectively. In contrast, the fractal dimension of the strings crosses over from
      that of self-avoiding walks for small strings, to simple random walks for longer,
      more strongly interacting, strings, corresponding to flexible polymers with
      screened excluded-volume interactions. We examine the appropriateness of
      identifying the size scales of either mobile particle clusters or strings with
      the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories.
      We find that the string size appears to be the most consistent measure of CRR for
      both the AG and RFOT models. Identifying strings or clusters with the "mosaic"
      length of the RFOT model relaxes the conventional assumption that the "entropic
      droplets" are compact. We also confirm the validity of the entropy formulation of
      the AG theory, constraining the exponent values of the RFOT theory. This
      constraint, together with the analysis of size scales, enables us to estimate the
      characteristic exponents of RFOT.

PMID- 23556794
TI  - Mechanical spectra of glass-forming liquids. I. Low-frequency bulk and shear
      moduli of DC704 and 5-PPE measured by piezoceramic transducers.
AB  - We present dynamic shear and bulk modulus measurements of supercooled tetraphenyl
      tetramethyl-trisiloxane (DC704) and 5-phenyl-4-ether over a range of temperatures
      close to their glass transition. The data are analyzed and compared in terms of
      time-temperature superposition (TTS), the relaxation time, and the spectral shape
      parameters. We conclude that TTS is obeyed to a good approximation for both the
      bulk and shear moduli. The loss-peak shapes are nearly identical, while the shear
      modulus relaxes faster than the bulk modulus. The temperature dependence of this
      decoupling of time scales is constant over the temperature range explored here.
      In addition, we demonstrate how one can measure reliably the DC shear viscosity
      over ten orders of magnitude by using the two measuring techniques in
      combination.

PMID- 23556795
TI  - Mechanical spectra of glass-forming liquids. II. Gigahertz-frequency longitudinal
      and shear acoustic dynamics in glycerol and DC704 studied by time-domain
      Brillouin scattering.
AB  - This paper presents and discusses the temperature and frequency dependence of the
      longitudinal and shear viscoelastic response at MHz and GHz frequencies of the
      intermediate glass former glycerol and the fragile glass former tetramethyl
      tetraphenyl-trisiloxane (DC704). Measurements were performed using the recently
      developed time-domain Brillouin scattering technique, in which acoustic waves are
      generated optically, propagated through nm thin liquid layers of different
      thicknesses, and detected optically after transmission into a transparent
      detection substrate. This allows for a determination of the frequency dependence
      of the speed of sound and the sound-wave attenuation. When the data are converted
      into mechanical moduli, a linear relationship between longitudinal and shear
      acoustic moduli is revealed, which is consistent with the generalized Cauchy
      relation. In glycerol, the temperature dependence of the shear acoustic
      relaxation time agrees well with literature data for dielectric measurements. In
      DC704, combining the new data with data from measurements obtained previously by
      piezo-ceramic transducers yields figures showing the longitudinal and shear sound
      velocities at frequencies from mHz to GHz over an extended range of temperatures.
      The shoving model's prediction for the relaxation time's temperature dependence
      is fairly well obeyed for both liquids as demonstrated from a plot with no
      adjustable parameters. Finally, we show that for both liquids the instantaneous
      shear modulus follows an exponential temperature dependence to a good
      approximation, as predicted by Granato's interstitialcy model.

PMID- 23556796
TI  - Temporal disconnectivity of the energy landscape in glassy systems.
AB  - An alternative graphical representation of the potential energy landscape (PEL)
      has been developed and applied to a binary Lennard-Jones glassy system, providing
      insight into the unique topology of the system's potential energy hypersurface.
      With the help of this representation one is able to monitor the different
      explored basins of the PEL, as well as how--and mainly when--subsets of basins
      communicate with each other via transitions in such a way that details of the
      prior temporal history have been erased, i.e., local equilibration between the
      basins in each subset has been achieved. In this way, apart from detailed
      information about the structure of the PEL, the system's temporal evolution on
      the PEL is described. In order to gather all necessary information about the
      identities of two or more basins that are connected with each other, we consider
      two different approaches. The first one is based on consideration of the time
      needed for two basins to mutually equilibrate their populations according to the
      transition rate between them, in the absence of any effect induced by the rest of
      the landscape. The second approach is based on an analytical solution of the
      master equation that explicitly takes into account the entire explored landscape.
      It is shown that both approaches lead to the same result concerning the topology
      of the PEL and dynamical evolution on it. Moreover, a "temporal disconnectivity
      graph" is introduced to represent a lumped system stemming from the initial one.
      The lumped system is obtained via a specially designed algorithm [N. Lempesis, D.
      G. Tsalikis, G. C. Boulougouris, and D. N. Theodorou, J. Chem. Phys. 135, 204507
      (2011)]. The temporal disconnectivity graph provides useful information about
      both the lumped and the initial systems, including the definition of "metabasins"
      as collections of basins that communicate with each other via transitions that
      are fast relative to the observation time. Finally, the two examined approaches
      are compared to an "on the fly" molecular dynamics-based algorithm [D. G.
      Tsalikis, N. Lempesis, G. C. Boulougouris, and D. N. Theodorou, J. Chem. Theory
      Comput. 6, 1307 (2010)].

PMID- 23556797
TI  - Theoretical reconstruction of realistic dynamics of highly coarse-grained cis-1,4
      polybutadiene melts.
AB  - The theory to reconstruct the atomistic-level chain diffusion from the
      accelerated dynamics that is measured in mesoscale simulations of the coarse
      grained system, is applied here to the dynamics of cis-1,4-polybutadiene melts
      where each chain is described as a soft interacting colloidal particle. The
      rescaling formalism accounts for the corrections in the dynamics due to the
      change in entropy and the change in friction that are a consequence of the coarse
      graining procedure. By including these two corrections the dynamics is rescaled
      to reproduce the realistic dynamics of the system described at the atomistic
      level. The rescaled diffusion coefficient obtained from mesoscale simulations of
      coarse-grained cis-1,4-polybutadiene melts shows good agreement with data from
      united atom simulations performed by Tsolou et al. [Macromolecules 38, 1478
      (2005)]. The derived monomer friction coefficient is used as an input to the
      theory for cooperative dynamics that describes the internal dynamics of a polymer
      moving in a transient regions of slow cooperative motion in a liquid of
      macromolecules. Theoretically predicted time correlation functions show good
      agreement with simulations in the whole range of length and time scales in which
      data are available.

PMID- 23556798
TI  - Random pinning glass transition: hallmarks, mean-field theory and renormalization
      group analysis.
AB  - We present a detailed analysis of glass transitions induced by pinning particles
      at random from an equilibrium configuration. We first develop a mean-field
      analysis based on the study of p-spin spherical disordered models and then obtain
      the three-dimensional critical behavior by the Migdal-Kadanoff real space
      renormalization group method. We unveil the important physical differences with
      the case in which particles are pinned from a random (or very high temperature)
      configuration. We contrast the pinning particles approach to the ones based on
      biasing dynamical trajectories with respect to their activity and on coupling to
      equilibrium configurations. Finally, we discuss numerical and experimental tests.

PMID- 23556799
TI  - Breakdown of the Stokes-Einstein relation in two, three, and four dimensions.
AB  - The breakdown of the Stokes-Einstein (SE) relation between diffusivity and
      viscosity at low temperatures is considered to be one of the hallmarks of glassy
      dynamics in liquids. Theoretical analyses relate this breakdown with the presence
      of heterogeneous dynamics, and by extension, with the fragility of glass formers.
      We perform an investigation of the breakdown of the SE relation in 2, 3, and 4
      dimensions in order to understand these interrelations. Results from simulations
      of model glass formers show that the degree of the breakdown of the SE relation
      decreases with increasing spatial dimensionality. The breakdown itself can be
      rationalized via the difference between the activation free energies for
      diffusivity and viscosity (or relaxation times) in the Adam-Gibbs relation in
      three and four dimensions. The behavior in two dimensions also can be understood
      in terms of a generalized Adam-Gibbs relation that is observed in previous work.
      We calculate various measures of heterogeneity of dynamics and find that the
      degree of the SE breakdown and measures of heterogeneity of dynamics are
      generally well correlated but with some exceptions. The two-dimensional systems
      we study show deviations from the pattern of behavior of the three- and four
      dimensional systems both at high and low temperatures. The fragility of the
      studied liquids is found to increase with spatial dimensionality, contrary to the
      expectation based on the association of fragility with heterogeneous dynamics.

PMID- 23556800
TI  - "Ideal glassformers" vs "ideal glasses": studies of crystal-free routes to the
      glassy state by "potential tuning" molecular dynamics, and laboratory
      calorimetry.
AB  - The ability of some liquids to vitrify during supercooling is usually seen as a
      consequence of the rates of crystal nucleation (and/or crystal growth) becoming
      small [D. R. Uhlmann, J. Non-Cryst. Solids 7, 337 (1972)]--and thus a matter of
      kinetics. However, there is evidence dating back to the empirics of coal
      briquetting for maximum trucking efficiency [D. Frenkel, Physics 3, 37 (2010)]
      that some object shapes find little advantage in self-assembly to ordered
      structures--meaning random packings prevail. Noting that key studies of non
      spherical object packing have never been followed from hard ellipsoids [A. Donev,
      F. H. Stillinger, P. M. Chaikin, and S. Torquato, Phys. Rev. Lett. 92, 255506
      (2004); A. Donev, I. Cisse, D. Sachs, E. A. Variano, F. H. Stillinger, R.
      Connelly, S. Torquato, and P. M. Chaikin, Science 303, 990 (2004)] or
      spherocylinders [S. R. Williams and A. P. Philipse, Phys. Rev. E 67, 051301
      (2003)] (diatomics excepted [S.-H. Chong, A. J. Moreno, F. Sciortino, and W. Kob,
      Phys. Rev. Lett. 94, 215701 (2005)] into the world of molecules with attractive
      forces, we have made a molecular dynamics study of crystal melting and glass
      formation on the Gay-Berne (G-B) model of ellipsoidal objects [J. G. Gay and B.
      J. Berne, J. Chem. Phys. 74, 3316 (1981)] across the aspect ratio range of the
      hard ellipsoid studies. Here, we report that in the aspect ratio range of maximum
      ellipsoid packing efficiency, various G-B crystalline states that cannot be
      obtained directly from the liquid, disorder spontaneously near 0 K and transform
      to liquids without any detectable enthalpy of fusion. Without claiming to have
      proved the existence of single component examples, we use the present
      observations, together with our knowledge of non-ideal mixing effects, to discuss
      the probable existence of "ideal glassformers"--single or multicomponent liquids
      that vitrify before ever becoming metastable with respect to crystals. We find
      evidence that "ideal glassformer" systems might also be highly fragile systems,
      approaching the "ideal glass" condition. We link this to the high "volume
      fragility" behavior observed in recent hard dumbbell studies at similar
      length/diameter ratios [R. Zhang and K. S. Schweitzer, J. Chem. Phys. 133, 104902
      (2010)]. The discussion suggests some unusual systems for laboratory study. Using
      differential scanning calorimetry detection of fusion points T(m), liquidus
      temperatures T(l), and glass transition temperatures T(g), we describe a system
      that would seem incapable of crystallizing before glass transition, i.e., an
      "ideal glassformer." The existence of crystal-free routes to the glassy state
      will eliminate precrystalline fluctuations as a source of the dynamic
      heterogeneities that are generally considered important in the discussion of the
      "glassy state problem [P. W. Anderson, Science 267, 1615 (1995)]."

PMID- 23556801
TI  - Charged particle velocity map image reconstruction with one-dimensional
      projections of spherical functions.
AB  - Velocity map imaging (VMI) is used in mass spectrometry and in angle resolved
      photo-electron spectroscopy to determine the lateral momentum distributions of
      charged particles accelerated towards a detector. VM-images are composed of
      projected Newton spheres with a common centre. The 2D images are usually
      evaluated by a decomposition into base vectors each representing the 2D
      projection of a set of particles starting from a centre with a specific velocity
      distribution. We propose to evaluate 1D projections of VM-images in terms of 1D
      projections of spherical functions, instead. The proposed evaluation algorithm
      shows that all distribution information can be retrieved from an adequately
      chosen set of 1D projections, alleviating the numerical effort for the
      interpretation of VM-images considerably. The obtained results produce directly
      the coefficients of the involved spherical functions, making the reconstruction
      of sliced Newton spheres obsolete.

PMID- 23556802
TI  - Coherent synchrotron radiation for broadband terahertz spectroscopy.
AB  - We present the first high resolution (10(-3) cm(-1)) interferometric measurements
      in the 200-750 GHz range using coherent synchrotron radiation, achieved with a
      low momentum compaction factor. The effect of microbunching on spectra is shown,
      depending on the bunch current. A high signal-to-noise ratio is reached thanks to
      an artifact correction system based on a double detection scheme. Combined to the
      broad emitted spectral range and high flux (up to 10(5) times the incoherent
      radiation), this study demonstrates that coherent synchrotron radiation can now
      be used for stability-demanding applications, such as gas-phase studies of
      unstable molecules.

PMID- 23556803
TI  - An optically transparent thin-layer electrochemical cell for the study of
      vibrational circular dichroism of chiral redox-active molecules.
AB  - An optically transparent thin-layer electrochemical (OTTLE) cell with a locally
      extended optical path has been developed in order to perform vibrational circular
      dichroism (VCD) spectroscopy on chiral molecules prepared in specific oxidation
      states by means of electrochemical reduction or oxidation. The new design of the
      electrochemical cell successfully addresses the technical challenges involved in
      achieving sufficient infrared absorption. The VCD-OTTLE cell proves to be a
      valuable tool for the investigation of chiral redox-active molecules.

PMID- 23556804
TI  - Momentum-imaging apparatus for the study of dissociative electron attachment
      dynamics.
AB  - An ion-momentum spectrometer is used to study the dissociative dynamics of
      electron attachment to molecules. A skimmed, supersonic gas jet is crossed with a
      pulsed beam of low-energy electrons, and the resulting negative ions are
      extracted toward a time- and position-sensitive detector. Calculations of the
      momentum in three dimensions may be used to determine the angular dependence of
      dissociative attachment as well as the energetics of the reaction.

PMID- 23556805
TI  - Design of a lens table for a double toroidal electron spectrometer.
AB  - We report here on the method we developed to build a lens table for a four
      element electrostatic transfer lens operated together with a double toroidal
      electron energy analyzer designed by one of us, and whose original design and
      further improvements are described in detail in Miron et al. [Rev. Sci. Instrum.
      68, 3728 (1997)] and Le Guen et al. [Rev. Sci. Instrum. 73, 3885 (2002)]. Both
      computer simulations and laboratory instrument tuning were performed in order to
      build this lens table. The obtained result was tested for a broad range of
      electron kinetic energies and analyzer pass energies. Based on this new lens
      table, allowing to easily computer control the spectrometer working conditions,
      we could routinely achieve an electron energy resolution ranging between 0.6% and
      0.8% of the analyzer pass energy, while the electron count rate was also
      significantly improved. The establishment of such a lens table is of high
      importance to relieve experimentalists from the tedious laboring of the lens
      optimization, which was previously necessary prior to any measurement. The
      described method can be adapted to any type of electron/ion energy analyzer, and
      will thus be interesting for all experimentalists who own, or plan to build or
      improve their charged particle energy analyzers.

PMID- 23556806
TI  - Compact high-resolution gamma-ray computed tomography system for multiphase flow
      studies.
AB  - In this paper, a compact high-resolution gamma-ray Computed Tomography (CompaCT)
      measurement system for multiphase flow studies and tomographic imaging of
      technical objects is presented. Its compact and robust design makes it
      particularly suitable for studies on industrial facilities and outdoor
      applications. Special care has been given to thermal ruggedness, shock
      resistance, and radiation protection. Main components of the system are a
      collimated (137)Cs isotopic source, a thermally stabilised modular high
      resolution gamma-ray detector arc with 112 scintillation detector elements, and a
      transportable rotary unit. The CompaCT allows full CT scans of objects with a
      diameter of up to 130 mm and can be operated with any tilting angle from 0
      degrees  (horizontal) to 90 degrees  (vertical).

PMID- 23556807
TI  - Broadband wide-angle dispersion measurements: instrumental setup, alignment, and
      pitfalls.
AB  - The construction, alignment, and performance of a setup for broadband wide-angle
      dispersion measurements, with emphasis on surface plasmon resonance (SPR)
      measurements, are presented in comprehensive detail. In contrast with most SPR
      instruments working with a monochromatic source, this setup takes advantage of a
      broadband/white light source and has full capability for automated angle vs.
      wavelength dispersion measurements for any arbitrary nanostructure array. A
      cylindrical prism is used rather than a triangular one in order to mitigate
      refraction induced effects and allow for such measurements. Although seemingly
      simple, this instrument requires use of many non-trivial methods in order to
      achieve proper alignment over all angles of incidence. Here we describe the
      alignment procedure for such a setup, the pitfalls introduced from the finite
      beam width incident onto the cylindrical prism, and deviations in the
      reflected/transmitted beam resulting from the finite thickness of the sample
      substrate. We address every one of these issues and provide experimental
      evidences on the success of this instrument and the alignment procedure used.

PMID- 23556808
TI  - Arbitrary waveform generator for quantum information processing with trapped
      ions.
AB  - Atomic ions confined in multi-electrode traps have been proposed as a basis for
      scalable quantum information processing. This scheme involves transporting ions
      between spatially distinct locations by use of time-varying electric potentials
      combined with laser or microwave pulses for quantum logic in specific locations.
      We report the development of a fast multi-channel arbitrary waveform generator
      for applying the time-varying electric potentials used for transport and for
      shaping quantum logic pulses. The generator is based on a field-programmable gate
      array controlled ensemble of 16-bit digital-to-analog converters with an update
      frequency of 50 MHz and an output range of +/-10 V. The update rate of the
      waveform generator is much faster than relevant motional frequencies of the
      confined ions in our experiments, allowing diabatic control of the ion motion.
      Numerous pre-loaded sets of time-varying voltages can be selected with 40 ns
      latency conditioned on real-time signals. Here we describe the device and
      demonstrate some of its uses in ion-based quantum information experiments,
      including speed-up of ion transport and the shaping of laser and microwave
      pulses.

PMID- 23556809
TI  - A gas-jet transport and catcher technique for on-line production of radioactive
      ion beams using an electron cyclotron resonance ion-source.
AB  - Radioactive ion beams (RIB) have been produced on-line, using a gas-jet recoil
      transport coupled Electron Cyclotron Resonance (ECR) ion-source at the VECC-RIB
      facility. Radioactive atoms/molecules carried through the gas-jet were stopped in
      a catcher placed inside the ECR plasma chamber. A skimmer has been used to remove
      bulk of the carrier gas at the ECR entrance. The diffusion of atoms/molecules
      through the catcher has been verified off-line using stable isotopes and on-line
      through transmission of radioactive reaction products. Beams of (14)O (71 s),
      (42)K (12.4 h), (43)K (22.2 h), and (41)Ar (1.8 h) have been produced by
      bombarding nitrogen and argon gas targets with proton and alpha particle beams
      from the K130 cyclotron at VECC. Typical measured intensity of RIB at the
      separator focal plane is found to be a few times 10(3) particles per second
      (pps). About 3.2 * 10(3) pps of 1.4 MeV (14)O RIB has been measured after
      acceleration through a radiofrequency quadrupole linac. The details of the gas
      jet coupled ECR ion-source and RIB production experiments are presented along
      with the plans for the future.

PMID- 23556810
TI  - A flash-lamp based device for fluorescence detection and identification of
      individual pollen grains.
AB  - We present a novel optical aerosol particle detector based on Xe flash lamp
      excitation and spectrally resolved fluorescence acquisition. We demonstrate its
      performances on three natural pollens acquiring in real-time scattering intensity
      at two wavelengths, sub-microsecond time-resolved scattering traces of the
      particles' passage in the focus, and UV-excited fluorescence spectra. We show
      that the device gives access to a rather specific detection of the bioaerosol
      particles.

PMID- 23556811
TI  - Simulation and optimization of a 10 A electron gun with electrostatic compression
      for the electron beam ion source.
AB  - Increasing the current density of the electron beam in the ion trap of the
      Electron Beam Ion Source (EBIS) in BNL's Relativistic Heavy Ion Collider facility
      would confer several essential benefits. They include increasing the ions' charge
      states, and therefore, the ions' energy out of the Booster for NASA applications,
      reducing the influx of residual ions in the ion trap, lowering the average power
      load on the electron collector, and possibly also reducing the emittance of the
      extracted ion beam. Here, we discuss our findings from a computer simulation of
      an electron gun with electrostatic compression for electron current up to 10 A
      that can deliver a high-current-density electron beam for EBIS. The magnetic
      field in the cathode-anode gap is formed with a magnetic shield surrounding the
      gun electrodes and the residual magnetic field on the cathode is (5 / 6) Gs. It
      was demonstrated that for optimized gun geometry within the electron beam current
      range of (0.5 / 10) A the amplitude of radial beam oscillations can be maintained
      close to 4% of the beam radius by adjusting the injection magnetic field
      generated by a separate magnetic coil. Simulating the performance of the gun by
      varying geometrical parameters indicated that the original gun model is close to
      optimum and the requirements to the precision of positioning the gun elements can
      be easily met with conventional technology.

PMID- 23556812
TI  - Key elements of space charge compensation on a low energy high intensity beam
      injector.
AB  - Space charge effect (SCE) along the beam line will decrease beam quality. Space
      charge compensation (SCC) with extra gas injection is a high-efficiency method to
      reduce SCE. In this paper, we will report the experimental results on the beam
      profile, potential distribution, beam emittance, and beam transmission efficiency
      of a 35 keV/90 mA H(+) beam and a 40 keV/10 mA He(+) beam compensated by Ar/Kr.
      The influence of gas type, gas flow, and injection location will be discussed.
      Emphasis is laid on the consideration of SCC when designing and commissioning a
      high intensity ion beam injector. Based on measured data, a new definition of
      space charge compensation degree is proposed.

PMID- 23556813
TI  - A large-acceptance beam-deceleration module for retrofitting into ion-source beam
      lines.
AB  - We describe a large-acceptance deceleration module capable of decelerating large
      emittance full-intensity ion beams typical of ECR ion sources to very low
      energies with high efficiency. The deceleration module is designed to permit
      convenient retrofitting into an existing beam line to replace, e.g., the first
      Faraday cup after magnetic analysis of the beam extracted from the ion source.
      For starting energies of 10 keV, and incident ion currents as large as 300 MUA,
      deceleration efficiencies have been measured to be greater than 80% for final
      energies as low as 70 eV. The decelerated beam intensity can be monitored either
      by insertion of a beam catcher floating at the final deceleration voltage or from
      the current to the exit grid itself, with suitable correction applied for the
      grid transparency factor. The behavior of the deceleration optics was modeled
      using SIMION, incorporating the effects of intra-beam space charge repulsion. We
      describe a recent application of this deceleration module to study near-surface
      He bubble and blister formation of a W target heated to 1250 K and irradiated
      with a 98 eV He ion beam with a flux of ~10(16) cm(-2) s(-1).

PMID- 23556814
TI  - A low energy beam transport system for proton beam.
AB  - A low energy beam transport (LEBT) system has been built for a compact pulsed
      hadron source (CPHS) at Tsinghua University in China. The LEBT, consisting of two
      solenoids and three short-drift sections, transports a pulsed proton beam of 60
      mA of energy of 50 keV to the entrance of a radio frequency quadrupole (RFQ).
      Measurement has shown a normalized RMS beam emittance less than 0.2 pi mm mrad at
      the end of the LEBT. Beam simulations were carried out to compare with the
      measurement and are in good agreement. Based on the successful CPHS LEBT
      development, a new LEBT for a China ADS projector has been designed. The features
      of the new design, including a beam chopper and beam simulations of the LEBT are
      presented and discussed along with CPHS LEBT development in this article.

PMID- 23556815
TI  - Measuring time of flight of fusion products in an inertial electrostatic
      confinement fusion device for spatial profiling of fusion reactions.
AB  - A new diagnostic has been developed that uses the time of flight (TOF) of the
      products from a nuclear fusion reaction to determine the location where the
      fusion reaction occurred. The TOF diagnostic uses charged particle detectors on
      opposing sides of the inertial electrostatic confinement (IEC) device that are
      coupled to high resolution timing electronics to measure the spatial profile of
      fusion reactions occurring between the two charged particle detectors. This
      diagnostic was constructed and tested by the University of Wisconsin-Madison
      Inertial Electrostatic Confinement Fusion Group in the IEC device, HOMER, which
      accelerates deuterium ions to fusion relevant energies in a high voltage (~100
      kV), spherically symmetric, electrostatic potential well [J. F. Santarius, G. L.
      Kulcinski, R. P. Ashley, D. R. Boris, B. B. Cipiti, S. K. Murali, G. R. Piefer,
      R. F. Radel, T. E. Radel, and A. L. Wehmeyer, Fusion Sci. Technol. 47, 1238
      (2005)]. The TOF diagnostic detects the products of D(d,p)T reactions and
      determines where along a chord through the device the fusion event occurred. The
      diagnostic is also capable of using charged particle spectroscopy to determine
      the Doppler shift imparted to the fusion products by the center of mass energy of
      the fusion reactants. The TOF diagnostic is thus able to collect spatial profiles
      of the fusion reaction density along a chord through the device, coupled with the
      center of mass energy of the reactions occurring at each location. This provides
      levels of diagnostic detail never before achieved on an IEC device.

PMID- 23556816
TI  - Scanning retarding field analyzer for plasma profile measurements in the boundary
      of the Alcator C-Mod tokamak.
AB  - A new Retarding Field Analyzer (RFA) head has been created for the outer-midplane
      scanning probe system on the Alcator C-Mod tokamak. The new probe head contains
      back-to-back retarding field analyzers aligned with the local magnetic field. One
      faces "upstream" into the field-aligned plasma flow and the other faces
      "downstream" away from the flow. The RFA was created primarily to benchmark ion
      temperature measurements of an ion sensitive probe; it may also be used to
      interrogate electrons. However, its construction is robust enough to be used to
      measure ion and electron temperatures up to the last-closed flux surface in C
      Mod. A RFA probe of identical design has been attached to the side of a limiter
      to explore direct changes to the boundary plasma due to lower hybrid heating and
      current drive. Design of the high heat flux (>100 MW/m(2)) handling probe and
      initial results are presented.

PMID- 23556817
TI  - Thermal neutron detection using a silicon pad detector and 6LiF removable
      converters.
AB  - A semiconductor detector coupled with a neutron converter is a good candidate for
      neutron detection, especially for its compactness and reliability if compared
      with other devices, such as (3)He tubes, even though its intrinsic efficiency is
      rather lower. In this paper we show a neutron detector design consisting of a 3
      cm * 3 cm silicon pad detector coupled with one or two external (6)LiF layers,
      enriched in (6)Li at 95%, placed in contact with the Si active surfaces. This
      prototype, first characterized and tested at INFN Laboratori Nazionali del Sud
      and then at JRC Ispra, was successfully shown to detect thermal neutrons with the
      expected efficiency and an outstanding gamma rejection capability.

PMID- 23556818
TI  - A compact capacitive probe for high-voltage diagnostic in Z-pinches.
AB  - A capacitive divider was arranged on Qiangguang pulsed power generator during a
      series of wire-array Z-pinch experiments. This divider was designed to measure
      the voltage acted on the gap of the cathode and anode boards. The probe has a
      compact construction and is conveniently assembled on the facility. It is also a
      cheap voltage probe and easy to build by research groups. The probe can monitor a
      1 MV high voltage with a 100 ns rise time. The calibration results showed that
      the probe had an attenuation ratio of 3.3 * 10(5) and a response time less than 5
      ns. The uncertainty was estimated to be 3%.

PMID- 23556819
TI  - A microwave interferometer for small and tenuous plasma density measurements.
AB  - The non-intrusive density measurement of the thin plasma produced by a mini
      helicon space thruster (HPH.com project) is a challenge, due to the broad density
      range (between 10(16) m(-3) and 10(19) m(-3)) and the small size of the plasma
      source (2 cm of diameter). A microwave interferometer has been developed for this
      purpose. Due to the small size of plasma, the probing beam wavelength must be
      small (lambda = 4 mm), thus a very high sensitivity interferometer is required in
      order to observe the lower density values. A low noise digital phase detector
      with a phase noise of 0.02 degrees  has been used, corresponding to a density of
      0.5 * 10(16) m(-3).

PMID- 23556820
TI  - A compact stilbene crystal neutron spectrometer for EAST D-D plasma neutron
      diagnostics.
AB  - A new compact stilbene crystal neutron spectrometer has been investigated and
      applied in the neutron emission spectroscopy on the EAST tokamak. A new
      components analysis method is presented to study the anisotropic light output in
      the stilbene crystal detector. A Geant4 code was developed to simulate the
      neutron responses in the spectrometer. Based on both the optimal light output
      function and the fitted pulse height resolution function, a reliable neutron
      response matrix was obtained by Geant4 simulations and validated by 2.5 MeV and
      14 MeV neutron measurements at a 4.5 MV Van de Graaff accelerator. The
      spectrometer was used to diagnose the ion temperature in plasma discharges with
      lower hybrid wave injection and ion cyclotron resonance heating on the EAST
      tokamak.

PMID- 23556821
TI  - Performance and characterization of the prototype nm-scale spatial resolution
      scanning multilayer Laue lenses microscope.
AB  - Synchrotron based x-ray microscopy established itself as a prominent tool for
      noninvasive investigations in many areas of science and technology. Many
      facilities around the world routinely achieve sub-micrometer resolution with a
      few instruments capable of imaging with the spatial resolution better than 100
      nm. With an ongoing effort to push the 2D/3D resolution down to 10 nm in the hard
      x-ray regime both fabrication of the nano-focusing optics and stability of a
      microscope become extremely challenging. In this work we present our approach to
      overcome technical challenges on the path towards high spatial resolution hard x
      ray microscopy and demonstrate the performance of a scanning fluorescence
      microscope equipped with the multilayer Laue lenses focusing optics.

PMID- 23556822
TI  - An active one-particle microrheometer: incorporating magnetic tweezers to total
      internal reflection microscopy.
AB  - We present a novel microrheometer by incorporating magnetic tweezers in the total
      internal reflection microscopy (TIRM) that enables measuring of viscoelastic
      properties of materials near solid surface. An evanescent wave generated by a
      solid/liquid interface in the TIRM is used as the incident light source in the
      microrheometer. When a probe particle (of a few micrometers diameter) moves near
      the interface, it can interact with the evanescent field and reflect its position
      with respect to the interface by the scattered light intensity. The exponential
      distance dependence of the evanescent field, on the one hand, makes this
      technique extremely sensitive to small changes from z-fluctuations of the probe
      (with a resolution of several nanometers), and on the other, it does not require
      imaging of the probe with high lateral resolution. Another distinct advantage is
      the high sensitivity in determining the z position of the probe in the absence of
      any labeling. The incorporated magnetic tweezers enable us to effectively
      manipulate the distance of the embedded particle from the interface either by a
      constant or an oscillatory force. The force ramp is easy to implement through a
      coil current ramp. In this way, the local viscous and elastic properties of a
      given system under different confinements can therefore be measured by resolving
      the near-surface particle motion. To test the feasibility of applying this
      microrheology to soft materials, we measured the viscoelastic properties of
      sucrose and poly(ethylene glycol) solutions and compared the results to bulk
      rheometry. In addition, we applied this technique in monitoring the structure and
      properties of deformable microgel particles near the flat surface.

PMID- 23556824
TI  - Surface-sensitive conductivity measurement using a micro multi-point probe
      approach.
AB  - An instrument for microscale electrical transport measurements in ultra-high
      vacuum is presented. The setup is constructed around collinear lithographically
      created multi-point probes with a contact spacing down to 500 nm. Most commonly,
      twelve-point probes are used. These probes are approached to the surface via
      piezoelectric positioners. Standard four-point resistance measurements can be
      performed using any combination of contacts out of the twelve available.
      Current/voltage measurements are taken semi-automatically for a variety of the
      possible contact configurations, effectively emulating measurements with an
      equidistant four-point probe for a wide range of contact spacings. In this way,
      it is possible to distinguish between bulk-like and surface-like conduction. The
      paper describes the design of the instrument and the approach to data and error
      analysis. Application examples are given for epitaxial graphene on SiC and
      degenerately doped Bi2Se3.

PMID- 23556823
TI  - Design of a scanning gate microscope for mesoscopic electron systems in a cryogen
      free dilution refrigerator.
AB  - We report on our design of a scanning gate microscope housed in a cryogen-free
      dilution refrigerator with a base temperature of 15 mK. The recent increase in
      efficiency of pulse tube cryocoolers has made cryogen-free systems popular in
      recent years. However, this new style of cryostat presents challenges for
      performing scanning probe measurements, mainly as a result of the vibrations
      introduced by the cryocooler. We demonstrate scanning with root-mean-square
      vibrations of 0.8 nm at 3 K and 2.1 nm at 15 mK in a 1 kHz bandwidth with our
      design. Using Coulomb blockade thermometry on a GaAs/AlGaAs gate-defined quantum
      dot, we demonstrate an electron temperature of 45 mK.

PMID- 23556825
TI  - An experimental system for high temperature X-ray diffraction studies with in
      situ mechanical loading.
AB  - An experimental system with in situ thermomechanical loading has been developed
      to enable high energy synchrotron x-ray diffraction studies of crystalline
      materials. The system applies and maintains loads of up to 2250 N in uniaxial
      tension or compression at a frequency of up to 100 Hz. The furnace heats the
      specimen uniformly up to a maximum temperature of 1200  degrees C in a variety of
      atmospheres (oxidizing, inert, reducing) that, combined with in situ mechanical
      loading, can be used to mimic processing and operating conditions of engineering
      components. The loaded specimen is reoriented with respect to the incident beam
      of x-rays using two rotational axes to increase the number of crystal
      orientations interrogated. The system was used at the Cornell High Energy
      Synchrotron Source to conduct experiments on single crystal silicon and
      polycrystalline Low Solvus High Refractory nickel-based superalloy. The data from
      these experiments provide new insights into how stresses evolve at the crystal
      scale during thermomechanical loading and complement the development of high
      fidelity material models.

PMID- 23556826
TI  - A 10 mK scanning tunneling microscope operating in ultra high vacuum and high
      magnetic fields.
AB  - We present design and performance of a scanning tunneling microscope (STM) that
      operates at temperatures down to 10 mK providing ultimate energy resolution on
      the atomic scale. The STM is attached to a dilution refrigerator with direct
      access to an ultra high vacuum chamber allowing in situ sample preparation. High
      magnetic fields of up to 14 T perpendicular and up to 0.5 T parallel to the
      sample surface can be applied. Temperature sensors mounted directly at the tip
      and sample position verified the base temperature within a small error margin.
      Using a superconducting Al tip and a metallic Cu(111) sample, we determined an
      effective temperature of 38 +/- 1 mK from the thermal broadening observed in the
      tunneling spectra. This results in an upper limit for the energy resolution of
      DeltaE = 3.5 kBT = 11.4 +/- 0.3 MUeV. The stability between tip and sample is 4
      pm at a temperature of 15 mK as demonstrated by topography measurements on a
      Cu(111) surface.

PMID- 23556827
TI  - A tool for measuring the bending length in thin wires.
AB  - Great effort is currently being put into the development and construction of the
      second generation, advanced gravitational wave detectors, Advanced Virgo and
      Advanced LIGO. The development of new low thermal noise suspensions of mirrors,
      based on the experience gained in the previous experiments, is part of this task.
      Quasi-monolithic suspensions with fused silica wires avoid the problem of rubbing
      friction introduced by steel cradle arrangements by directly welding the wires to
      silica blocks bonded to the mirror. Moreover, the mechanical loss level
      introduced by silica (phifs ~ 10(-7) in thin fused silica wires) is by far less
      than the one associated with steel. The low frequency dynamical behaviour of the
      suspension can be computed and optimized, provided that the wire bending shape
      under pendulum motion is known. Due to the production process, fused silica wires
      are thicker near the two ends (necks), so that analytical bending computations
      are very complicated. We developed a tool to directly measure the low frequency
      bending parameters of fused silica wires, and we tested it on the wires produced
      for the Virgo+ monolithic suspensions. The working principle and a set of test
      measurements are presented and explained.

PMID- 23556828
TI  - Design of a new reactor-like high temperature near ambient pressure scanning
      tunneling microscope for catalysis studies.
AB  - Here, we present the design of a new reactor-like high-temperature near ambient
      pressure scanning tunneling microscope (HT-NAP-STM) for catalysis studies. This
      HT-NAP-STM was designed for exploration of structures of catalyst surfaces at
      atomic scale during catalysis or under reaction conditions. In this HT-NAP-STM,
      the minimized reactor with a volume of reactant gases of ~10 ml is thermally
      isolated from the STM room through a shielding dome installed between the reactor
      and STM room. An aperture on the dome was made to allow tip to approach to or
      retract from a catalyst surface in the reactor. This dome minimizes thermal
      diffusion from hot gas of the reactor to the STM room and thus remains STM head
      at a constant temperature near to room temperature, allowing observation of
      surface structures at atomic scale under reaction conditions or during catalysis
      with minimized thermal drift. The integrated quadrupole mass spectrometer can
      simultaneously measure products during visualization of surface structure of a
      catalyst. This synergy allows building an intrinsic correlation between surface
      structure and its catalytic performance. This correlation offers important
      insights for understanding of catalysis. Tests were done on graphite in ambient
      environment, Pt(111) in CO, graphene on Ru(0001) in UHV at high temperature and
      gaseous environment at high temperature. Atom-resolved surface structure of
      graphene on Ru(0001) at 500 K in a gaseous environment of 25 Torr was identified.

PMID- 23556829
TI  - Reduction of low-density lipoprotein cholesterol, plasma viscosity, and whole
      blood viscosity by the application of pulsed corona discharges and filtration.
AB  - The present study investigated the feasibility of applying pulsed corona
      discharges to blood plasma to reduce the viscosity of blood plasma and whole
      blood. Blood plasma was separated from blood cells, treated with corona
      discharges, and filtered before it was re-mixed with blood cells. Plasma
      viscosity (PV), whole blood viscosity (WBV), and low-density lipoprotein (LDL)-c
      concentration were measured before and after the corona treatment and filtration.
      Both PV and WBV increased in the case of the corona treatment only, whereas both
      of them decreased in the case of the corona treatment plus filtration. In
      particular, the LDL-c decreased in the case of the corona treatment plus
      filtration by 31.5% from the baseline value. The effect of the corona treatment
      on the reduction of the WBV was significant at low shear rates, but not at high
      shear rates, suggesting that the precipitation of the molecules in blood plasma
      by the corona treatment and subsequent removal may suppress the aggregation of
      erythrocytes and improve rheological properties of blood.

PMID- 23556830
TI  - X-ray intravital microscopy for functional imaging in rat hearts using
      synchrotron radiation coronary microangiography.
AB  - An X-ray intravital microscopy technique was developed to enable in vivo
      visualization of the coronary, cerebral, and pulmonary arteries in rats without
      exposure of organs and with spatial resolution in the micrometer range and
      temporal resolution in the millisecond range. We have refined the system
      continually in terms of the spatial resolution and exposure time. X-rays
      transmitted through an object are detected by an X-ray direct-conversion type
      detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution
      has been improved to 6 MUm, yielding sharp images of small arteries. The exposure
      time has been shortened to around 2 ms using a new rotating-disk X-ray shutter,
      enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray
      intravital microscopy technique were extracted from measurements of the smallest
      detectable vessel size and detection of the vessel function. The smallest
      diameter vessel viewed for measurements is determined primarily by the
      concentration of iodinated contrast material. The iodine concentration depends on
      the injection technique. We used ex vivo rat hearts under Langendorff perfusion
      for accurate evaluation. After the contrast agent is injected into the origin of
      the aorta in an isolated perfused rat heart, the contrast agent is delivered
      directly into the coronary arteries with minimum dilution. The vascular internal
      diameter response of coronary arterial circulation is analyzed to evaluate the
      vessel function. Small blood vessels of more than about 50 MUm diameters were
      visualized clearly at heart rates of around 300 beats/min. Vasodilation compared
      to the control was observed quantitatively using drug manipulation. Furthermore,
      the apparent increase in the number of small vessels with diameters of less than
      about 50 MUm was observed after the vasoactive agents increased the diameters of
      invisible small blood vessels to visible sizes. This technique is expected to
      offer the potential for direct investigation of mechanisms of vascular
      dysfunctions.

PMID- 23556831
TI  - Design and experiment of a directional coupler for X-band long pulse high power
      microwaves.
AB  - Higher power and longer pulse are the trend of the development of high power
      microwave (HPM), and then some problems emerge in measuring the power of HPM
      because rf breakdown is easier to occur under the circumstance of high power (the
      level of gigawatt) and long pulse (about 100 ns). In order to measure the power
      of the dominant TM01 mode of an X-band long pulse overmoded HPM source, a
      directional coupler with stable coupling coefficient, high directivity, and high
      power handling capacity in wide band is investigated numerically and
      experimentally. At the central frequency 9.4 GHz, the simulation results show
      that the coupling coefficient is -59.6 dB with the directivity of 35 dB and the
      power handling capacity of 2 GW. The coupling coefficient is calibrated to be
      accordant with the simulation results. The high power tests are performed on an X
      band long pulse HPM source, whose output mode is mainly TM01 mode, and the
      results show that the measured power and waveform of the directional coupler have
      a good consistency with the far-field measuring results.

PMID- 23556832
TI  - A compact 45 kV curve tracer with picoampere current measurement capability.
AB  - This paper discusses a compact high voltage curve tracer for high voltage
      semiconductor device characterization. The system sources up to 3 mA at up to 45
      kV in dc conditions. It measures from 328 V to 60 kV with 15 V resolution and
      from 9.4 pA to 4 mA with 100 fA minimum resolution. Control software for the
      system is written in Microsoft Visual C# and features real-time measurement
      control and IV plotting, arc-protection and detection, an electrically isolated
      universal serial bus interface, and easy data exporting capabilities. The system
      has survived numerous catastrophic high voltage device-under-test arcing failures
      with no loss of measurement capability or system damage. Overall sweep times are
      typically under 2 min, and the curve tracer system was used to characterize the
      blocking performance of high voltage ceramic capacitors, high voltage silicon
      carbide photoconductive semiconductor switches, and high voltage coaxial cable.

PMID- 23556833
TI  - Discrete transistor measuring and matching using a solid core oven.
AB  - This paper presents transistor measurements done at a constant temperature. The
      aim in this research was to develop a reliable and repeatable method for
      measuring and searching transistor pairs with similar parameters, as in certain
      applications it is advantageous to use transistors from the same production batch
      due to the significant variability in batches from different manufacturers.
      Transistor manufacturing methods are well established, but due to the large
      variability in tolerance, not even transistors from the same manufacturing batch
      have identical properties. Transistors' electrical properties are also strongly
      temperature-dependent. Therefore, when measuring transistor properties, the
      temperature must be kept constant. For the measurement process, a solid-core oven
      providing stable temperature was implemented. In the oven, the base-to-emitter
      voltage (VBE) and DC-current gain (beta) of 32 transistors could be measured
      simultaneously. The oven's temperature was controlled with a programmable
      thermostat, which allowed accurate constant temperature operation. The oven is
      formed by a large metal block with an individual chamber for each transistor to
      be measured. Isolation of individual transistors and the highly thermally
      conductive metal core structure prevent thermal coupling between transistors. The
      oven enables repeatable measurements, and thus measurements between different
      batches are comparable. In this research study, the properties of over 5000
      transistors were measured and the variance of the aforementioned properties was
      analyzed.

PMID- 23556834
TI  - Two-port microwave calibration at millikelvin temperatures.
AB  - In this work we introduce a system for 2-port microwave calibration at
      millikelvin temperatures operating at the coldest stage of a dilution
      refrigerator by use of an adapted thru-reflect-line algorithm. We show that this
      can be an effective tool for characterizing common 50 Omega microwave components
      with better than 0.1 dB accuracy at temperatures that are relevant to many
      current experiments in superconducting quantum information.

PMID- 23556835
TI  - An alternate approach to the production of radioisotopes for nuclear medicine
      applications.
AB  - There is a growing need for the production of radioisotopes for both diagnostic
      and therapeutic medical applications. Radioisotopes that are produced using the
      (n,gamma) or (gamma,n) reactions, however, typically result in samples with low
      specific activity (radioactivity/gram) due to the high abundance of target
      material of the same element. One method to effectively remove the isotopic
      impurity is electro-magnetic mass separation. An Ion Source Test Facility has
      been constructed at TRIUMF to develop high-intensity, high-efficiency, reliable
      ion sources for purification of radioactive isotopes, particularly those used in
      nuclear medicine. In progress studies are presented.

PMID- 23556836
TI  - In situ broadband cryogenic calibration for two-port superconducting microwave
      resonators.
AB  - We introduce an improved microwave calibration method for use in a cryogenic
      environment, based on a traditional three-standard calibration, the Thru-Reflect
      Line (TRL) calibration. The modified calibration method takes advantage of
      additional information from multiple measurements of an ensemble of realizations
      of a superconducting resonator, as a new pseudo-Open standard, to correct errors
      in the TRL calibration. We also demonstrate an experimental realization of this
      in situ broadband cryogenic calibration system utilizing cryogenic switches. All
      calibration measurements are done in the same thermal cycle as the measurement of
      the resonator (requiring only an additional 20 min), thus avoiding 4 additional
      thermal cycles for traditional TRL calibration (which would require an additional
      12 days). The experimental measurements on a wave-chaotic microwave billiard
      verify that the new method significantly improves the measured scattering matrix
      of a high-quality-factor superconducting resonator.

PMID- 23556837
TI  - Steady heat conduction-based thermal conductivity measurement of single walled
      carbon nanotubes thin film using a micropipette thermal sensor.
AB  - In this paper, we describe the thermal conductivity measurement of single-walled
      carbon nanotubes thin film using a laser point source-based steady state heat
      conduction method. A high precision micropipette thermal sensor fabricated with a
      sensing tip size varying from 2 MUm to 5 MUm and capable of measuring thermal
      fluctuation with resolution of +/-0.01 K was used to measure the temperature
      gradient across the suspended carbon nanotubes (CNT) film with a thickness of 100
      nm. We used a steady heat conduction model to correlate the temperature gradient
      to the thermal conductivity of the film. We measured the average thermal
      conductivity of CNT film as 74.3 +/- 7.9 W m(-1) K(-1) at room temperature.

PMID- 23556838
TI  - Simultaneous measurement of thermal conductivity and heat capacity of bulk and
      thin film materials using frequency-dependent transient thermoreflectance method.
AB  - The increasing interest in the extraordinary thermal properties of nanostructures
      has led to the development of various measurement techniques. Transient
      thermoreflectance method has emerged as a reliable measurement technique for
      thermal conductivity of thin films. In this method, the determination of thermal
      conductivity usually relies much on the accuracy of heat capacity input. For new
      nanoscale materials with unknown or less-understood thermal properties, it is
      either questionable to assume bulk heat capacity for nanostructures or difficult
      to obtain the bulk form of those materials for a conventional heat capacity
      measurement. In this paper, we describe a technique for simultaneous measurement
      of thermal conductivity kappa and volumetric heat capacity C of both bulk and
      thin film materials using frequency-dependent time-domain thermoreflectance
      (TDTR) signals. The heat transfer model is analyzed first to find how different
      combinations of kappa and C determine the frequency-dependent TDTR signals.
      Simultaneous measurement of thermal conductivity and volumetric heat capacity is
      then demonstrated with bulk Si and thin film SiO2 samples using frequency
      dependent TDTR measurement. This method is further testified by measuring both
      thermal conductivity and volumetric heat capacity of novel hybrid organic
      inorganic thin films fabricated using the atomic/molecular layer deposition.
      Simultaneous measurement of thermal conductivity and heat capacity can
      significantly shorten the development/discovery cycle of novel materials.

PMID- 23556839
TI  - Temperature measurements of heated microcantilevers using scanning
      thermoreflectance microscopy.
AB  - We report the development of scanning thermoreflectance thermometry and its
      application for steady and dynamic temperature measurement of a heated
      microcantilever. The local thermoreflectance signal of the heated microcantilever
      was calibrated to temperature while the cantilever was under steady and periodic
      heating operation. The temperature resolution of our approach is 0.6 K, and the
      spatial resolution is 2 MUm, which are comparable to micro-Raman thermometry.
      However, the temporal resolution of our approach is about 10 MUsec, which is
      significantly faster than micro-Raman thermometry. When the heated
      microcantilever is periodically heated with frequency up to 100 kHz, we can
      measure both the in-phase and out-of-phase components of the temperature
      oscillation. For increasing heating frequency, the measured cantilever AC
      temperature distribution tends to be confined in the vicinity of the heater
      region and becomes increasingly out of phase with the driving signal. These
      results compare well with finite element simulations.

PMID- 23556840
TI  - A poly(dimethylsiloxane) based prism for surface plasmon resonance imaging system
      and its application for gas detection.
AB  - This paper presents a surface plasmon resonance (SPR) imaging system based on a
      low-cost, convenient poly(dimethylsiloxane) (PDMS) prism featured with a close
      contact with the gold film. Compared to conventional glass prism, both numerical
      simulations and experimental studies indicated a deeper but wider absorption peak
      with a higher coupling angle for the PDMS based prism. System repeatability was
      quantified by the cycled detection of helium and air, with the effect of the flow
      rate investigated. Furthermore, five types of gases (nitrogen, air, oxygen,
      hydrogen, and helium) were detected and differentiated by the SPR system, with a
      calculated sensitivity of 5 * 10(-6) RIU.

PMID- 23556841
TI  - Non-invasive timing of gas gun-launched projectiles using external surface
      mounted optical fiber-Bragg grating strain gauges.
AB  - Non-invasive detection methods for tracking gun-launched projectiles are
      important not only for assessment of gun performance but are also essential for
      timing a variety of diagnostics, for example, to investigate plate-impact events
      for shock compression experiments. Measurement of the time of passage of a
      projectile moving inside of the gun barrel can be achieved by detection of the
      transient hoop strain induced in the barrel of a light-gas gun by the passage of
      the projectile using external, barrel surface-mounted optical fiber-Bragg grating
      strain gauges. Optical fiber-Bragg gratings have been implemented and their
      response characterized on single-stage and two-stage light gas guns routinely
      used for dynamic experimentation at Los Alamos National Laboratory. Two
      approaches, using either broadband or narrowband illumination, were used to
      monitor changes in the Bragg wavelength of the fiber-Bragg gratings. The second
      approach, using narrowband laser illumination, offered the highest sensitivity.
      The feasibility of using these techniques to generate early, pre-event signals
      useful for triggering high-latency diagnostics was demonstrated.

PMID- 23556842
TI  - A crossflow filtration system for constant permeate flux membrane fouling
      characterization.
AB  - Membrane fouling is often characterized using a crossflow filtration apparatus.
      Typically, the transmembrane pressure (TMP) difference is fixed, and the flux is
      allowed to decline as the membrane fouls and the resistance to mass transfer
      increases. However, as flux varies, so too does the rate at which foulants are
      brought to the membrane surface, so the observed fouling behavior is not solely
      the result of membrane/foulant interactions. Constant flux experiments, where the
      permeate flux is fixed and the TMP difference varies, minimize such variations in
      the hydrodynamic conditions at the membrane surface, but constant TMP difference
      experiments dominate the fouling literature because they are more straightforward
      to execute than constant flux experiments. Additionally, most industrial water
      purification membrane installations operate at constant flux rather than at
      constant TMP. Here, we describe the construction and operation of a constant flux
      crossflow fouling apparatus. System measurement accuracy was validated by
      comparison of pure water permeance measurements to values specified by the
      membrane manufacturer, reported elsewhere, and measured by another technique.
      Fouling experiments were performed with two membrane/foulant systems: polysulfone
      ultrafiltration membranes with a soybean oil emulsion foulant and PVDF
      microfiltration membranes with a polystyrene latex bead suspension foulant.
      Automatic permeate flux control facilitated flux stepping experiments, which are
      commonly used to determine the threshold flux or critical flux of a
      membrane/foulant pair. Comparison of a flux stepping experiment with a literature
      report yielded good agreement.

PMID- 23556843
TI  - Flux concentration and modulation based magnetoresistive sensor with integrated
      planar compensation coils.
AB  - 1/f noise is one of the main noise sources of magnetoresistive (MR) sensors,
      which can cause intrinsic detection limit at low frequency. To suppress this
      noise, the solution of flux concentration and vertical motion modulation (VMM)
      has been proposed. Magnetic hysteresis in MR sensors is another problem, which
      degrades their response linearity and detection ability. To reduce this impact,
      the method of pulse magnetization and magnetic compensation field with integrated
      planar coils has been introduced. A flux concentration and VMM based
      magnetoresistive prototype sensor with integrated planar coils was fabricated
      using microelectromechanical-system technology. The response linearity of the
      prototype sensors is improved from 0.8% to 0.12%. The noise level is reduced near
      to the thermal noise level, and the low-frequency detection ability of the
      prototype sensor is enhanced with a factor of more than 80.

PMID- 23556844
TI  - An air flow sensor for neonatal mechanical ventilation applications based on a
      novel fiber-optic sensing technique.
AB  - In this work, a simple and low-cost air flow sensor, based on a novel fiber-optic
      sensing technique has been developed for monitoring air flows rates supplied by a
      neonatal ventilator to support infants in intensive care units. The device is
      based on a fiber optic sensing technique allowing (a) the immunity to light
      intensity variations independent by measurand and (b) the reduction of typical
      shortcomings affecting all biomedical fields (electromagnetic interference and
      patient electrical safety). The sensing principle is based on the measurement of
      transversal displacement of an emitting fiber-optic cantilever due to action of
      air flow acting on it; the fiber tip displacement is measured by means of a
      photodiode linear array, placed in front of the entrance face of the emitting
      optical fiber in order to detect its light intensity profile. As the measurement
      system is based on a detection of the illumination pattern, and not on an
      intensity modulation technique, it results less sensitive to light intensity
      fluctuation independent by measurand than intensity-based sensors. The considered
      technique is here adopted in order to develop two different configurations for an
      air flow sensor suitable for the measurement of air flow rates typically
      occurring during mechanical ventilation of newborns: a mono-directional and a bi
      directional transducer have been proposed. A mathematical model for the air flow
      sensor is here proposed and a static calibration of two different arrangements
      has been performed: a measurement range up to 3.00 * 10(-4) m(3)/s (18.0 l/min)
      for the mono-directional sensor and a measurement range of +/-3.00 * 10(-4)
      m(3)/s (+/-18.0 l/min) for the bi-directional sensor are experimentally
      evaluated, according to the air flow rates normally encountered during tidal
      breathing of infants with a mass lower than 10 kg. Experimental data of static
      calibration result in accordance with the proposed theoretical model: for the
      mono-directional configuration, the coefficient of determination r(2) is equal to
      0.997; for the bi-directional configuration, the coefficient of determination
      r(2) is equal to 0.990 for positive flows (inspiration) and 0.988 for negative
      flows (expiration). Measurement uncertainty deltaQ of air flow rate has been
      evaluated by means of the propagation of distributions and the percentage error
      in the arrangement of bi-directional sensor ranges from a minimum of about 0.5%
      at -18.0 l/min to a maximum of about 9% at -12.0 l/min.

PMID- 23556845
TI  - Compact prototype apparatus for reducing the circle of confusion down to 40 nm
      for x-ray nanotomography.
AB  - We have constructed a compact prototype apparatus for active correction of circle
      of confusion during rotational motion. Our system combines fiber optic
      interferometry as a sensing element, the reference cylinder along with the
      nanopositioning system, and a robust correction algorithm. We demonstrate dynamic
      correction of run-out errors down to 40 nm; the resolution is limited by ambient
      environment and accuracy of correcting nanopositioners. Our approach provides a
      compact solution for in-vacuum scanning nanotomography x-ray experiments with a
      potential to reach sub-nm level of correction.

PMID- 23556846
TI  - Coupling a Knudsen reactor with the short lived radioactive tracer (13)N for
      atmospheric chemistry studies.
AB  - A Knudsen cell flow reactor was coupled to an online gas phase source of the
      short-lived radioactive tracer (13)N to study the adsorption of nitrogen oxides
      on ice at temperatures relevant for the upper troposphere. This novel approach
      has several benefits over the conventional coupling of a Knudsen cell with a mass
      spectrometer. Experiments at lower partial pressures close to atmospheric
      conditions are possible. The uptake to the substrate is a direct observable of
      the experiment. Operation of the experiment in continuous or pulse mode allows to
      retrieve steady state uptake kinetics and more details of adsorption and
      desorption kinetics.

PMID- 23556847
TI  - Design and fabrication of a bending rotation fatigue test rig for in situ
      electrochemical analysis during fatigue testing of NiTi shape memory alloy wires.
AB  - The current investigation proposes a novel method for simultaneous assessment of
      the electrochemical and structural fatigue properties of nickel-titanium shape
      memory alloy (NiTi SMA) wires. The design and layout of an in situ
      electrochemical cell in a custom-made bending rotation fatigue (BRF) test rig is
      presented. This newly designed test rig allows performing a wide spectrum of
      experiments for studying the influence of fatigue on corrosion and vice versa.
      This can be achieved by performing ex situ and/or in situ measurements. The
      versatility of the combined electrochemical/mechanical test rig is demonstrated
      by studying the electrochemical behavior of NiTi SMA wires in 0.9% NaCl
      electrolyte under load. The ex situ measurements allow addressing various issues,
      for example, the influence of pre-fatigue on the localized corrosion resistance,
      or the influence of hydrogen on fatigue life. Ex situ experiments showed that a
      pre-fatigued wire is more susceptible to localized corrosion. The synergetic
      effect can be concluded from the polarization studies and specifically from an in
      situ study of the open circuit potential (OCP) transients, which sensitively
      react to the elementary repassivation events related to the local failure of the
      oxide layer. It can also be used as an indicator for identifying the onset of the
      fatigue failure.

PMID- 23556848
TI  - An electric stimulation system for electrokinetic particle manipulation in
      microfluidic devices.
AB  - Microfluidic devices have grown significantly in the number of applications.
      Microfabrication techniques have evolved considerably; however, electric
      stimulation systems for microdevices have not advanced at the same pace. Electric
      stimulation of micro-fluidic devices is an important element in particle
      manipulation research. A flexible stimulation instrument is desired to perform
      configurable, repeatable, automated, and reliable experiments by allowing users
      to select the stimulation parameters. The instrument presented here is a
      configurable and programmable stimulation system for electrokinetic-driven
      microfluidic devices; it consists of a processor, a memory system, and a user
      interface to deliver several types of waveforms and stimulation patterns. It has
      been designed to be a flexible, highly configurable, low power instrument capable
      of delivering sine, triangle, and sawtooth waveforms with one single frequency or
      two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output
      voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a
      single time period or as a sequence of different signals for different time
      periods. This stimulation system can be applied as a research tool where
      manipulation of particles suspended in liquid media is involved, such as biology,
      medicine, environment, embryology, and genetics. This system has the potential to
      lead to new schemes for laboratory procedures by allowing application specific
      and user defined electric stimulation. The development of this device is a step
      towards portable and programmable instrumentation for electric stimulation on
      electrokinetic-based microfluidic devices, which are meant to be integrated with
      lab-on-a-chip devices.

PMID- 23556849
TI  - An automated high throughput tribometer for adhesion, wear, and friction
      measurements.
AB  - Understanding the origin and correlation of different surface properties under a
      multitude of operating conditions is critical in tribology. Diverse tribological
      properties and a lack of a single instrument to measure all make it difficult to
      compare and correlate properties, particularly in light of the wide range of
      interfaces commonly investigated. In the current work, a novel automated
      tribometer has been designed and validated, providing a unique experimental
      platform capable of high throughput adhesion, wear, kinetic friction, and static
      friction measurements. The innovative design aspects are discussed that allow for
      a variety of probes, sample surfaces, and testing conditions. Critical components
      of the instrument and their design criteria are described along with examples of
      data collection schemes. A case study is presented with multiple surface
      measurements performed on a set of characteristic substrates. Adhesion, wear,
      kinetic friction, and static friction are analyzed and compared across surfaces,
      highlighting the comprehensive nature of the surface data that can be generated
      using the automated high throughput tribometer.

PMID- 23556850
TI  - Thin conductive diamond films as beam intensity monitors for soft x-ray
      beamlines.
AB  - Quantitative analysis of X-ray absorption and dichroism data requires knowledge
      of the beamline photon flux during the measurements. We show that thin conductive
      (B-doped) diamond thin films can be an alternative to the widely used gold meshes
      for monitoring the beam intensity of soft X-ray beamlines in situ. Limited by the
      carbon extended x-ray absorption fine structure oscillations, the diamond films
      become applicable beginning from about 600 eV photon energy, where the important
      transition metal edges and the rare-earth edges are found. The 100 nm and 250 nm
      thick free-standing diamond films were grown and tested against standard gold
      meshes in real-life dichroism experiments performed at beamline ID08 of the
      European Synchrotron Radiation Facility, Grenoble, France. Quantitative agreement
      was found between the two experimental data sets. The films feature an extremely
      high transmission of about 90% and, at the same time, yield a sufficiently strong
      and clean reference signal. Furthermore, the thin films do not affect the shape
      of the transmitted beam. X-rays passing mesh-type monitors are subject to
      diffraction effects, which widen the beam and become particularly disturbing for
      small beamsizes in the micrometer range.

PMID- 23556851
TI  - A combined matrix isolation spectroscopy and cryosolid positron moderation
      apparatus.
AB  - We describe the design, construction, and operation of a novel apparatus for
      investigating efficiency improvements in thin-film cryogenic solid positron
      moderators. We report results from solid neon, argon, krypton, and xenon positron
      moderators which illustrate the capabilities and limitations of our apparatus. We
      integrate a matrix isolation spectroscopy diagnostic within a reflection-geometry
      positron moderation system. We report the optical thickness, impurity content,
      and impurity trapping site structures within our moderators determined from
      infrared absorption spectra. We use a retarding potential analyzer to modulate
      the flow of slow positrons, and report positron currents vs. retarding potential
      for the different moderators. We identify vacuum ultraviolet emissions from
      irradiated Ne moderators as the source of spurious signals in our channel
      electron multiplier slow positron detection channel. Our design is also unusual
      in that it employs a sealed radioactive Na-22 positron source which can be
      translated relative to, and isolated from, the cryogenic moderator deposition
      substrate. This allows us to separate the influences on moderator efficiency of
      surface contamination by residual gases from those of accumulated radiation
      damage.

PMID- 23556852
TI  - Tungstate sharpening: a versatile method for extending the profile of ultra sharp
      tungsten probes.
AB  - The benefits of a new electrochemical etching method for the controlled
      sharpening of sub-micron tungsten probes are demonstrated. The proposed technique
      only utilizes the insulating effect of the WO4(2-) by-product which offers more
      practical ways of controlling the process parameters. The electrosharpening
      method was fully automated through the analysis of the process current, bulk
      coulometry, shadowgraphs, and time lapse microscopy. Tip radii smaller than 15 nm
      were maintained over a wide range of controlled lengths up to 4.5 mm with conic
      angles of less than 1 degrees .

PMID- 23556853
TI  - Note: an environmental cell for transient spectroscopy on solid samples in
      controlled atmospheres.
AB  - A sample cell for performing time-resolved spectroscopy on solid samples within
      an atmosphere of controlled vapor composition was designed and constructed.
      Control over vapor composition was accomplished using a combination of passive
      sealing and chemical agents. Performance characteristics especially well-suited
      to studies using femtosecond mid-infrared spectroscopy were achieved by the use
      of ultrathin silicon nitride windows and a rapid and reproducible sample cell
      exchange mechanism.

PMID- 23556854
TI  - Note: Size effects on the tensile response of top-down fabricated Si nanobeams.
AB  - The tensile response of top-down fabricated sc-Si nanobeams is inferred from the
      fitting of stress-strain data obtained under tensile loading conditions over a
      large range of deformation. The testing is performed using MEMS structures
      consisting of two connected beams; a highly stressed silicon-nitride (SiN) beam
      connected to a sc-Si specimen beam. The high tensile stress component present
      upon the deposition of the SiN loads the sc-Si beam once the entire structure is
      released. The strain and stress values are extracted independently, respectively,
      by scanning electron microscopy inspection and vibration frequency measurement of
      the released tensile MEMS structures. The tensile tests are undertaken for six
      thicknesses to determine the dependence of the elastic response on dimensions.
      The Young's modulus shows a variation of 40% for thicknesses ranging from 200 to
      30 nm.

PMID- 23556855
TI  - Note: Near-field imaging of thermal radiation at low temperatures by passive
      millimeter-wave microscopy.
AB  - Imaging of thermal radiation with a spatial resolution below the diffraction
      limit is demonstrated with a passive millimeter-wave microscope. This technique
      utilizes a sensitive radiometric receiver in combination with a scanning near
      field microscope. Experiments were performed at 50 GHz (lambda = 6 mm) with
      sample temperatures ranging from room temperature down to 160 K, and the
      performance was shown to be superior to that achieved with passive imaging
      systems in the infrared region. The images are affected by non-uniformities in
      the transmission of thermal radiation from the sample to the receiver via the
      near-field probe and the reflection of thermal radiation back to the receiver
      from the probe. The effects of these non-uniformities were successfully removed
      using a sample image acquired by active measurements using a vector network
      analyzer.

PMID- 23556856
TI  - Note: Broadband cavity ring-down spectroscopy of an intra-cavity bulk sample.
AB  - A cavity ring-down (CRD) setup equipped with a pulsed broadband light source (480
      nm <= lambda <= 650 nm) and a multichannel detection system (temporal gate width
      Deltatau = 20 ns) is used to simultaneously record the optical loss spectrum of
      an intra-cavity CaF2 sample and its changes upon transverse ArF laser irradiation
      at 193 nm. The CRD setup with mirrors of high reflectivity (R > 99.93%) allows to
      register loss changes of 5 * 10(-5) with a spectral resolution of 0.3 nm in less
      than 2 min.

PMID- 23556857
TI  - Note: Simple calibration of the counting-rate dependence of the timing shift of
      single photon avalanche diodes by photon interval analysis.
AB  - The counting-rate dependence of the temporal response of single photon avalanche
      diodes (SPADs) is a critical issue for the accurate determination of the
      fluorescence lifetime. In this study, the response of SPADs was examined with
      analyzing the time interval of the detected photons. The results clearly show
      that the shift of the detection timing causes the counting-rate dependence of the
      temporal response, and this timing shift is solely determined by the time
      interval from the preceding photon. We demonstrate that this timing instability
      is readily calibrated by utilizing the macrotime data taken with the time-tag
      mode that is implemented in the time-correlated single photon counting modules.

PMID- 23556858
TI  - Note: Alignment/focus dependent core-line sensitivity for quantitative chemical
      analysis in hard x-ray photoelectron spectroscopy using a hemispherical electron
      analyzer.
AB  - X-ray photoelectron spectroscopy is an established technique for quantitative
      chemical analysis requiring accurate peak intensity analysis. We present evidence
      of focus/alignment dependence of relative peak intensities for peaks over a broad
      kinetic energy range with a hemispherical electron analyzer operated in a
      position imaging mode. A decrease of over 50% in the Ag 2p3/2 to Ag 3d ratio is
      observed in a Ag specimen. No focus/alignment dependence is observed when using
      an angular imaging mode, necessitating the use of angular mode for quantitative
      chemical analysis.

PMID- 23556859
TI  - Note: a real-time beam current density meter.
AB  - We have developed a real-time beam current density meter for charged particle
      beams. It measures the mean current density by collimating a uniform and large
      diameter primary beam. The suppression of the secondary electrons and the
      deflection of the beam were simulated, and it was tested with a 105 keV Ar(7+)
      ion beam.

PMID- 23556860
TI  - Note: Dynamic analysis of a robotic fish motion with a caudal fin with vertical
      phase differences.
AB  - In this paper, a robotic fish with a caudal fin with vertical phase differences
      is studied, especially focusing on the energy consumption. Energies for thrusting
      a conventional robotic fish and one with caudal fin with vertical phase
      differences are obtained and compared each other. It is shown that a robotic fish
      with a caudal fin with vertical phase differences can save more energy, which
      implies the efficient thrusting via a vertically waving caudal fin.

PMID- 23556861
TI  - Note: Rapid offset reduction of impedance bridges taking into account
      instrumental damping and phase shifting.
AB  - The sensitivity of an imperfectly balanced impedance bridge is limited by the
      remaining offset voltage. Here, we present a procedure for offset reduction in
      impedance measurements using a lock-in amplifier, by applying a complex
      compensating voltage external to the bridge. This procedure takes into account
      instrumental damping and phase shifting, which generally occur at the high end of
      the operational frequency range. Measurements demonstrate that the output of the
      circuit rapidly converges to the instrumentally limited noise at any frequency.

PMID- 23556862
TI  - Note: Detecting flow velocity with high purity semiconducting single-walled
      carbon nanotubes.
AB  - We report the measurement of fluid velocity on a semiconducting single-walled
      carbon nanotubes film in a microfluidic channel. To investigate the mechanism
      related to electrical signal change, we performed various experiments along with
      changing the flow velocity, the ion concentration and liquid viscosity, etc. Our
      result suggests that the sensing of flow velocity is a closely related to a
      pulsating asymmetrical thermal ratchet model. The electric signal change was
      strongly dependent on the electrode alignment, and the channel width of the
      sample. As the result, we achieved highly sensitive detection of the fluid,
      roughly 4 times greater than previous results.

PMID- 23556863
TI  - Note: a simple thermal gradient annealing unit for the treatment of thin films.
AB  - A gradient annealing cell has been developed for the high-throughput study of
      thermal annealing effects on thin-film libraries in different environments. The
      inexpensive gradient annealing unit permits temperature gradients as large as 28 
      degrees C/mm and can accommodate samples ranging in length from 13 mm to 51 mm.
      The system was validated by investigating the effects of annealing temperature on
      the crystallinity, resistivity, and transparency of tin-doped indium oxide
      deposited on a glass substrate by magnetron sputtering. The unit developed in
      this work will permit the rapid optimization of materials properties such as
      crystallinity, homogeneity, and conductivity across a variety of applications.

PMID- 23556866
TI  - Risk of medical imaging.

PMID- 23556867
TI  - The need for performance standards in clinical translation and adoption of
      fluorescence molecular imaging.

PMID- 23556868
TI  - Why research sex differences and similarities?

PMID- 23556869
TI  - Point/Counterpoint. IGRT has limited clinical value due to lack of accurate tumor
      delineation.

PMID- 23556871
TI  - The effects of mapping CT images to Monte Carlo materials on GEANT4 proton
      simulation accuracy.
AB  - PURPOSE: Monte Carlo simulations of radiation therapy require conversion from
      Hounsfield units (HU) in CT images to an exact tissue composition and density.
      The number of discrete densities (or density bins) used in this mapping affects
      the simulation accuracy, execution time, and memory usage in GEANT4 and other
      Monte Carlo code. The relationship between the number of density bins and CT
      noise was examined in general for all simulations that use HU conversion to
      density. Additionally, the effect of this on simulation accuracy was examined for
      proton radiation. METHODS: Relative uncertainty from CT noise was compared with
      uncertainty from density binning to determine an upper limit on the number of
      density bins required in the presence of CT noise. Error propagation analysis was
      also performed on continuously slowing down approximation range calculations to
      determine the proton range uncertainty caused by density binning. These results
      were verified with Monte Carlo simulations. RESULTS: In the presence of even
      modest CT noise (5 HU or 0.5%) 450 density bins were found to only cause a 5%
      increase in the density uncertainty (i.e., 95% of density uncertainty from CT
      noise, 5% from binning). Larger numbers of density bins are not required as CT
      noise will prevent increased density accuracy; this applies across all types of
      Monte Carlo simulations. Examining uncertainty in proton range, only 127 density
      bins are required for a proton range error of <0.1 mm in most tissue and <0.5 mm
      in low density tissue (e.g., lung). CONCLUSIONS: By considering CT noise and
      actual range uncertainty, the number of required density bins can be restricted
      to a very modest 127 depending on the application. Reducing the number of density
      bins provides large memory and execution time savings in GEANT4 and other Monte
      Carlo packages.

PMID- 23556870
TI  - First study of on-treatment volumetric imaging during respiratory gated VMAT.
AB  - PURPOSE: To obtain on-treatment volumetric patient anatomy during respiratory
      gated volumetric modulated arc therapy (VMAT). METHODS: On-board imaging device
      integrated with Linacs offers a viable tool for obtaining patient anatomy during
      radiation treatment delivery. In this study, the authors acquired beam-level kV
      images during gated VMAT treatments using a Varian TrueBeamTMSTx Linac. These kV
      projection images are triggered by a respiratory gating signal and can be
      acquired immediately before treatment MV beam on at every breathing cycle during
      delivery. Because the kV images are acquired with an on-board imaging device
      during a rotational arc therapy, they provide the patient anatomical information
      from many different angles or projection views (typically 20-40). To reconstruct
      the volumetric image representing patient anatomy during the VMAT treatment, the
      authors used a compressed sensing method with a fast first-order optimization
      algorithm. The conventional FDK reconstruction was also used for comparison
      purposes. The method was tested on a dynamic anthropomorphic physical phantom as
      well as a lung patient. RESULTS: The reconstructed volumetric images for a
      dynamic anthropomorphic physical phantom and a lung patient showed clearly
      visible soft-tissue target as well as other anatomical structures, with the
      proposed compressed sensing-based image reconstruction method. Compared with FDK,
      the compressed sensing method leads to a ~ two and threefold increase in contrast
      to-noise ratio around the target area in the phantom and patient case,
      respectively. CONCLUSIONS: The proposed technique provides on-treatment
      volumetric patient anatomy, with only a fraction (<10%) of the imaging dose used
      in conventional CBCT procedures. This anatomical information may be valuable for
      geometric verification and treatment guidance, and useful for verification of
      treatment dose delivery, accumulation, and adaptation in the future.

PMID- 23556872
TI  - Proton beam scattering system optimization for clinical and research
      applications.
AB  - PURPOSE: To develop and test a method for optimizing and constructing a dual
      scattering system in passively scattered proton therapy. METHODS: A beam optics
      optimization algorithm was developed to optimize the thickness of the first
      scatterer (S1) and the profile (of both the high-Z material and Lexan) of the
      second scatterer (S2) to deliver a proton beam matching a given set of
      parameters, including field diameter, fluence, flatness, and symmetry. A new
      manufacturing process was also tested that allows the contoured second scattering
      foil to be created much more economically and quickly using Cerrobend casting.
      Two application-specific scattering systems were developed and tested using both
      experimental and Monte Carlo techniques to validate the optimization process
      described. RESULTS: A scattering system was optimized and constructed to deliver
      large uniform irradiations of radiobiology samples at low dose rates. This system
      was successfully built and tested using film and ionization chambers. The system
      delivered a uniform radiation field of 50 cm diameter (to a dose of +/- 7% of the
      central axis) while the depth dose profile could be tuned to match the
      specifications of the particular investigator using modulator wheels and range
      shifters. A second scattering system for intermediate field size (4 cm < diameter
      < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments
      was also developed and tested using GEANT4. This system improved beam efficiency
      by over 70% compared with existing scattering systems while maintaining field
      flatness and depth dose profile. In both cases the proton range uniformity across
      the radiation field was maintained, further indicating the accuracy of the energy
      loss formalism in the optimization algorithm. CONCLUSIONS: The methods described
      allow for rapid prototyping of scattering foils to meet the demands of both
      research and clinical beam delivery applications in proton therapy.

PMID- 23556873
TI  - Determination of gonad doses during robotic stereotactic radiosurgery for various
      tumor sites.
AB  - PURPOSE: The authors evaluated the absorbed dose received by the gonads during
      robotic stereotactic radiosurgery (SRS) for the treatment of different tumor
      localizations. METHODS: The authors measured the gonad doses during the treatment
      of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and
      actual patients. The computerized tomography images were transferred to the
      treatment planning system. The contours of tumor and critical organs were
      delineated on each slice, and treatment plans were generated. Measurements for
      gonad doses were taken from the geometric projection of the ovary onto the skin
      for female patients, and from the scrotal skin for male patients by attaching
      films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife
      (Accuray Inc., Sunnyvale, CA). RESULTS: The median gonadal doses with TLD and
      film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy
      (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian
      doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy
      (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular
      doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306
      Gy (range, 0.065-2.25 Gy). CONCLUSIONS: Gonad doses are below sterility threshold
      in robotic SRS for different tumor localizations. However, particular attention
      should be given to gonads during robotic SRS for pelvic tumors.

PMID- 23556874
TI  - A gEUD-based inverse planning technique for HDR prostate brachytherapy:
      feasibility study.
AB  - PURPOSE: The purpose of this work was to study the feasibility of a new inverse
      planning technique based on the generalized equivalent uniform dose for image
      guided high dose rate (HDR) prostate cancer brachytherapy in comparison to
      conventional dose-volume based optimization. METHODS: The quality of 12 clinical
      HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning
      Optimization) is compared with alternative plans, which were produced through
      inverse planning using the generalized equivalent uniform dose (gEUD). All the
      common dose-volume indices for the prostate and the organs at risk were
      considered together with radiobiological measures. The clinical effectiveness of
      the different dose distributions was investigated by comparing dose volume
      histogram and gEUD evaluators. RESULTS: Our results demonstrate the feasibility
      of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A
      statistically significant decrease in D10 or/and final gEUD values for the organs
      at risk (urethra, bladder, and rectum) was found while improving dose homogeneity
      or dose conformity of the target volume. CONCLUSIONS: Following the promising
      results of gEUD-based optimization in intensity modulated radiation therapy
      treatment optimization, as reported in the literature, the implementation of a
      similar model in HDR brachytherapy treatment plan optimization is suggested by
      this study. The potential of improved sparing of organs at risk was shown for
      various gEUD-based optimization parameter protocols, which indicates the ability
      of this method to adapt to the user's preferences.

PMID- 23556875
TI  - Audiovisual biofeedback improves motion prediction accuracy.
AB  - PURPOSE: The accuracy of motion prediction, utilized to overcome the system
      latency of motion management radiotherapy systems, is hampered by irregularities
      present in the patients' respiratory pattern. Audiovisual (AV) biofeedback has
      been shown to reduce respiratory irregularities. The aim of this study was to
      test the hypothesis that AV biofeedback improves the accuracy of motion
      prediction. METHODS: An AV biofeedback system combined with real-time respiratory
      data acquisition and MR images were implemented in this project. One-dimensional
      respiratory data from (1) the abdominal wall (30 Hz) and (2) the thoracic
      diaphragm (5 Hz) were obtained from 15 healthy human subjects across 30 studies.
      The subjects were required to breathe with and without the guidance of AV
      biofeedback during each study. The obtained respiratory signals were then
      implemented in a kernel density estimation prediction algorithm. For each of the
      30 studies, five different prediction times ranging from 50 to 1400 ms were
      tested (150 predictions performed). Prediction error was quantified as the root
      mean square error (RMSE); the RMSE was calculated from the difference between the
      real and predicted respiratory data. The statistical significance of the
      prediction results was determined by the Student's t-test. RESULTS: Prediction
      accuracy was considerably improved by the implementation of AV biofeedback. Of
      the 150 respiratory predictions performed, prediction accuracy was improved 69%
      (103/150) of the time for abdominal wall data, and 78% (117/150) of the time for
      diaphragm data. The average reduction in RMSE due to AV biofeedback over unguided
      respiration was 26% (p < 0.001) and 29% (p < 0.001) for abdominal wall and
      diaphragm respiratory motion, respectively. CONCLUSIONS: This study was the first
      to demonstrate that the reduction of respiratory irregularities due to the
      implementation of AV biofeedback improves prediction accuracy. This would result
      in increased efficiency of motion management techniques affected by system
      latencies used in radiotherapy.

PMID- 23556876
TI  - Accuracy verification of infrared marker-based dynamic tumor-tracking irradiation
      using the gimbaled x-ray head of the Vero4DRT (MHI-TM2000).
AB  - PURPOSE: To verify the accuracy of an infrared (IR) marker-based dynamic tumor
      tracking irradiation system (IR tracking) using the gimbaled x-ray head of the
      Vero4DRT (MHI-TM2000). METHODS: The gimbaled 6-MV C-band x-ray head of the
      Vero4DRT can swing along the pan-and-tilt direction to track a moving target.
      During beam delivery, the Vero4DRT predicts the future three-dimensional (3D)
      target position in real time using a correlation model [four-dimensional (4D)
      model] between the target and IR marker motion, and then continuously transfers
      the corresponding tracking orientation to the gimbaled x-ray head. The 4D
      modeling error (E4DM) and the positional tracking error (EP) were defined as the
      difference between the predicted and measured positions of the target in 4D
      modeling and as the difference between the tracked and measured positions of the
      target during irradiation, respectively. For the clinical application of IR
      tracking, we assessed the relationship between E4DM and EP for three 1D
      sinusoidal (peak-to-peak amplitude [A]: 20-40 mm, breathing period [T]: 2-4 s),
      five 1D phase-shifted sinusoidal (A: 20 mm, T: 4 s, phase shift [tau]: 0.2-2 s),
      and six 3D patient respiratory patterns. RESULTS: The difference between the 95th
      percentile of the absolute EP (EP (95)) and the mean (MU) + two standard
      deviations (SD) of absolute E4DM (E4DM (MU+2SD)) was within +/- 1 mm for all
      motion patterns. As the absolute correlation between the target and IR marker
      motions decreased from 1.0 to 0.1 for the 1D phase-shifted sinusoidal patterns,
      the E4DM (MU+2SD) and EP (95) increased linearly, from 0.4 to 3.0 mm (R = -0.98)
      and from 0.5 to 2.2 mm (R = -0.95), respectively. There was a strong positive
      correlation between E4DM (MU+2SD) and EP (95) in each direction [(lateral,
      craniocaudal, anteroposterior) = (0.99, 0.98, 1.00)], even for the 3D respiratory
      patterns; thus, EP (95) was readily estimated from E4DM (MU+2SD). CONCLUSIONS:
      Positional tracking errors correlated strongly with 4D-modeling errors in IR
      tracking. Thus, the accuracy of the 4D model must be verified before treatment,
      and margins are required to compensate for the 4D-modeling error.

PMID- 23556877
TI  - Evaluation of multiple image-based modalities for image-guided radiation therapy
      (IGRT) of prostate carcinoma: a prospective study.
AB  - PURPOSE: Setup errors and prostate intrafraction motion are main sources of
      localization uncertainty in prostate cancer radiation therapy. This study
      evaluates four different imaging modalities 3D ultrasound (US), kV planar images,
      cone-beam computed tomography (CBCT), and implanted electromagnetic transponders
      (Calypso/Varian) to assess inter- and intrafraction localization errors during
      intensity-modulated radiation therapy based treatment of prostate cancer.
      METHODS: Twenty-seven prostate cancer patients were enrolled in a prospective IRB
      approved study and treated to a total dose of 75.6 Gy (1.8 Gy/fraction). Overall,
      1100 fractions were evaluated. For each fraction, treatment targets were
      localized using US, kV planar images, and CBCT in a sequence defined to determine
      setup offsets relative to the patient skin tattoos, intermodality differences,
      and residual errors for each patient and patient cohort. Planning margins,
      following van Herk's formalism, were estimated based on error distributions.
      Calypso-based localization was not available for the first eight patients,
      therefore centroid positions of implanted gold-seed markers imaged prior to and
      immediately following treatment were used as a motion surrogate during treatment.
      For the remaining 19 patients, Calypso transponders were used to assess prostate
      intrafraction motion. RESULTS: The means (MU), and standard deviations (SD) of
      the systematic (Sigma) and random errors (sigma) of interfraction prostate shifts
      (relative to initial skin tattoo positioning), as evaluated using CBCT, kV, and
      US, averaged over all patients and fractions, were: [MU CBCT = (-1.2, 0.2, 1.1)
      mm, Sigma CBCT = (3.0, 1.4, 2.4) mm, sigma CBCT = (3.2, 2.2, 2.5) mm], [MUkV = (
      2.9, -0.4, 0.5) mm, Sigma kV = (3.4, 3.1, 2.6) mm, sigma kV = (2.9, 2.0, 2.4)
      mm], and [MU US = (-3.6, -1.4, 0.0) mm, Sigma US = (3.3, 3.5, 2.8) mm, sigma US =
      (4.1, 3.8, 3.6) mm], in the anterior-posterior (A/P), superior-inferior (S/I),
      and the left-right (L/R) directions, respectively. In the treatment protocol,
      adjustment of couch was guided by US images. Residual setup errors as assessed by
      kV images were found to be: MU residual = (-0.4, 0.2, 0.2) mm, Sigma residual =
      (1.0, 1.0,0.7) mm, and sigma residual = (2.5, 2.3, 1.8) mm. Intrafraction
      prostate motion, evaluated using electromagnetic transponders, was: MU intrafxn =
      (0.0, 0.0, 0.0) mm, Sigma intrafxn = (1.3, 1.5, 0.6) mm, and sigma intrafxn =
      (2.6, 2.4, 1.4) mm. Shifts between pre- and post-treatment kV images were: MU
      kV(post-pre) = (-0.3, 0.8, -0.2), Sigma kV(post-pre) = (2.4, 2.7, 2.1) mm, and
      sigma kV(post-pre) = (2.7, 3.2, 3.1) mm. Relative to skin tattoos, planning
      margins for setup error were within 10-11 mm for all image-based modalities. The
      use of image guidance was shown to reduce these margins to less than 5 mm.
      Margins to compensate for both residual setup (interfraction) errors as well as
      intrafraction motion were 6.6, 6.8, and 3.9 mm in the A/P, S/I, and L/R
      directions, respectively. CONCLUSIONS: Analysis of interfraction setup errors,
      performed with US, CBCT, planar kV images, and electromagnetic transponders, from
      a large dataset revealed intermodality shifts were comparable (within 3-4 mm).
      Interfraction planning margins, relative to setup based on skin marks, were
      generally within the 10 mm prostate-to-planning target volume margin used in our
      clinic. With image guidance, interfraction residual planning margins were reduced
      to approximately less than 4 mm. These findings are potentially important for
      dose escalation studies using smaller margins to better protect normal tissues.

PMID- 23556878
TI  - Characterization of optical transport effects on EPID dosimetry using Geant4.
AB  - PURPOSE: Current amorphous silicon electronic portal imaging devices (a-Si EPIDs)
      that are frequently used in radiotherapy applications employ a metal
      plate/phosphor screen configuration to optimize x-ray detection efficiency. The
      phosphor acts to convert x rays into an optical signal that is detected by an
      underlying photodiode array. The dosimetric response of EPIDs has been well
      characterized, in part through the development of computational models. Such
      models, however, have generally made simplifying assumptions with regards to the
      transport of optical photons within these detectors. The goal of this work was to
      develop and experimentally validate a new Monte Carlo (MC) model of an a-Si EPID
      that simulates both x-ray and optical photon transport in a self-contained
      manner. Using this model the authors establish a definitive characterization of
      the effects of optical transport on the dosimetric response of a-Si EPIDs
      employing gadolinium oxysulfide phosphor screens. METHODS: The Geant4 MC toolkit
      was used to develop a model of an a-Si EPID that employs standard electromagnetic
      and optical physics classes. The sensitivity of EPID response to uncertainties in
      optical transport parameters was evaluated by investigating their effects on the
      EPID point spread function (PSF). An optical blur kernel was also calculated to
      isolate the component of the PSF resulting purely from optical transport. A 6 MV
      photon source model was developed and integrated into the MC model to investigate
      EPID dosimetric response. Field size output factors and relative dose profiles
      were calculated for a set of open fields by separately scoring energy deposited
      in the phosphor and optical absorption events in the photodiode. These were then
      compared to quantify effects resulting from optical photon transport. The EPID
      model was validated against experimental measurements taken using a research
      EPID. RESULTS: Optical photon scatter within the phosphor screen noticeably
      broadened the PSF. Variations in optical transport parameters reported in the
      literature caused fluctuations in the PSF full width at half maximum (FWHM) and
      full width at tenth maximum (FWTM) of less than 3% and 5%, respectively,
      confirming model robustness. Greater deviations (up to 9.5% and 36% for FWHM and
      FWTM, respectively) were observed when optical parameters were largely different
      from reference values. When scoring energy deposition in the phosphor, measured
      and calculated output factors agreed within statistical uncertainties and at
      least 94% of the MC simulated profile data points passed 3%/3 mm gamma-index
      criterion for all field sizes considered. Despite statistical uncertainties in
      optical simulations arising from computational limitations, no differences were
      observed between optical and energy deposition profiles. CONCLUSIONS: Simulations
      demonstrated noticeable blurring of the EPID PSF when scoring optical absorption
      events in the photodiode relative to energy deposition in the phosphor. However,
      modeling the standard electromagnetic transport alone should suffice when using
      MC methods to predict EPID dose-response to static, open 6 MV fields with a
      standard a-Si photodiode array. Therefore, using energy deposition in the
      phosphor as a surrogate for EPID dose-response is a valid approach that should
      not require additional corrections for optical transport effects in current a-Si
      EPIDs employing phosphor screens.

PMID- 23556879
TI  - BrachyView: proof-of-principle of a novel in-body gamma camera for low dose-rate
      prostate brachytherapy.
AB  - PURPOSE: The conformity of the achieved dose distribution to the treatment plan
      strongly correlates with the accuracy of seed implantation in a prostate
      brachytherapy treatment procedure. Incorrect seed placement leads to both short
      and long term complications, including urethral and rectal toxicity. The authors
      present BrachyView, a novel concept of a fast intraoperative treatment planning
      system, to provide real-time seed placement information based on in-body gamma
      camera data. BrachyView combines the high spatial resolution of a pixellated
      silicon detector (Medipix2) with the volumetric information acquired by a
      transrectal ultrasound (TRUS). The two systems will be embedded in the same probe
      so as to provide anatomically correct seed positions for intraoperative planning
      and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method
      using the real position of the seeds. The purpose of this paper is to demonstrate
      the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole
      collimator to reconstruct the real-time 3D position of low dose-rate
      brachytherapy seeds in a phantom. METHODS: BrachyView incorporates three Medipix2
      detectors coupled to a multipinhole collimator. Three-dimensionally triangulated
      seed positions from multiple planar images are used to determine the seed
      placement in a PMMA prostate phantom in real time. MATLAB codes were used to test
      the reconstruction method and to optimize the device geometry. RESULTS: The
      results presented in this paper show a 3D position reconstruction accuracy of the
      seed in the range of 0.5-3 mm for a 10-60 mm seed-to-detector distance interval
      (Z direction), respectively. The BrachyView system also demonstrates a spatial
      resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2
      detector plane, comparable to the theoretical value calculated for an equivalent
      gamma camera arrangement. The authors successfully demonstrated the capability of
      BrachyView for real-time imaging (using a 3 s data acquisition time) of different
      brachytherapy seed configurations (with an activity of 0.05 U) throughout a 60 *
      60 * 60 mm(3) Perspex prostate phantom. CONCLUSIONS: The newly developed
      miniature gamma camera component of BrachyView, with its high spatial resolution
      and real time capability, allows accurate 3D localization of seeds in a prostate
      phantom. Combination of the gamma camera with TRUS in a single probe will
      complete the BrachyView system.

PMID- 23556880
TI  - Objected constrained registration and manifold learning: a new patient setup
      approach in image guided radiation therapy of thoracic cancer.
AB  - PURPOSE: The management of thoracic malignancies with radiation therapy is
      complicated by continuous target motion. In this study, a real time motion
      analysis approach is proposed to improve the accuracy of patient setup. METHODS:
      For 11 lung cancer patients a long training fluoroscopy was acquired before the
      first treatment, and multiple short testing fluoroscopies were acquired weekly at
      the pretreatment patient setup of image guided radiotherapy (IGRT). The data
      analysis consisted of three steps: first a 4D target motion model was constructed
      from 4DCT and projected to the training fluoroscopy through deformable
      registration. Then the manifold learning method was used to construct a 2D
      subspace based on the target motion (kinetic) and location (static) information
      in the training fluoroscopy. Thereafter the respiratory phase in the testing
      fluoroscopy was determined by finding its location in the subspace. Finally, the
      phase determined testing fluoroscopy was registered to the corresponding 4DCT to
      derive the pretreatment patient position adjustment for the IGRT. The method was
      tested on clinical image sets and numerical phantoms. RESULTS: The registration
      successfully reconstructed the 4D motion model with over 98% volume similarity in
      4DCT, and over 95% area similarity in the training fluoroscopy. The machine
      learning method derived the phase values in over 98% and 93% test images of the
      phantom and patient images, respectively, with less than 3% phase error. The
      setup approach achieved an average accumulated setup error less than 1.7 mm in
      the cranial-caudal direction and less than 1 mm in the transverse plane. All
      results were validated against the ground truth of manual delineations by an
      experienced radiation oncologist. The expected total time for the pretreatment
      setup analysis was less than 10 s. CONCLUSIONS: By combining the registration and
      machine learning, the proposed approach has the potential to improve the accuracy
      of pretreatment setup for patients with thoracic malignancy.

PMID- 23556881
TI  - Microionization chamber air-kerma calibration coefficients as a function of
      photon energy for x-ray spectra in the range of 20-250 kVp relative to 60Co.
AB  - PURPOSE: To investigate the applicability of a wide range of microionization
      chambers for reference dosimetry measurements in low- and medium-energy x-ray
      beams. METHODS: Measurements were performed with six cylindrical microchamber
      models, as well as one scanning chamber and two Farmer-type chambers for
      comparison purposes. Air-kerma calibration coefficients were determined at the
      University of Wisconsin Accredited Dosimetry Calibration Laboratory for each
      chamber for a range of low- and medium-energy x-ray beams (20-250 kVp), with
      effective energies ranging from 11.5 keV to 145 keV, and a (60)Co beam. A low-Z
      proof-of-concept microchamber was developed and calibrated with and without a
      high-Z silver epoxy on the collecting electrode. RESULTS: All chambers composed
      of low-Z materials (Z <= 13), including the Farmer-type chambers, the scanning
      chamber, and the PTW TN31014 and the proof-of-concept microchambers, exhibited
      air-kerma calibration coefficients with little dependence on the quality of the
      beam. These chambers typically exhibited variations in calibration coefficients
      of less than 3% with the beam quality, for medium energy beams. However,
      variations in air-kerma calibration coefficients of greater than 50% were
      measured over the range of medium-energy x-ray beams for each of the
      microchambers containing high-Z collecting electrodes (Z > 13). For these high-Z
      chambers, which include the Exradin A14SL and A16 chambers, the PTW TN31006
      chamber, the IBA CC01 chamber, and the proof-of-concept chamber containing
      silver, the average variation in air-kerma calibration coefficients between any
      two calibration beams was nearly 25% over the entire range of beam qualities
      investigated. CONCLUSIONS: Due to the strong energy dependence observed with
      microchambers containing high-Z components, these chambers may not be suitable
      dosimeters for kilovoltage x-ray applications, as they do not meet the TG-61
      requirements. It is recommended that only microchambers containing low-Z
      materials (Z <= 13) be considered for air-kerma calibrations for reference
      dosimetry in low- and medium-energy x-ray beams.

PMID- 23556882
TI  - Experimental evaluations of the accuracy of 3D and 4D planning in robotic
      tracking stereotactic body radiotherapy for lung cancers.
AB  - PURPOSE: Due to the complexity of 4D target tracking radiotherapy, the accuracy
      of this treatment strategy should be experimentally validated against established
      standard 3D technique. This work compared the accuracy of 3D and 4D dose
      calculations in respiration tracking stereotactic body radiotherapy (SBRT).
      METHODS: Using the 4D planning module of the CyberKnife treatment planning
      system, treatment plans for a moving target and a static off-target cord
      structure were created on different four-dimensional computed tomography (4D-CT)
      datasets of a thorax phantom moving in different ranges. The 4D planning system
      used B-splines deformable image registrations (DIR) to accumulate dose
      distributions calculated on different breathing geometries, each corresponding to
      a static 3D-CT image of the 4D-CT dataset, onto a reference image to compose a 4D
      dose distribution. For each motion, 4D optimization was performed to generate a
      4D treatment plan of the moving target. For comparison with standard 3D planning,
      each 4D plan was copied to the reference end-exhale images and a standard 3D dose
      calculation was followed. Treatment plans of the off-target structure were first
      obtained by standard 3D optimization on the end-exhale images. Subsequently, they
      were applied to recalculate the 4D dose distributions using DIRs. All dose
      distributions that were initially obtained using the ray-tracing algorithm with
      equivalent path-length heterogeneity correction (3D EPL and 4D EPL) were
      recalculated by a Monte Carlo algorithm (3D MC and 4D MC) to further investigate
      the effects of dose calculation algorithms. The calculated 3D EPL, 3D MC, 4D EPL,
      and 4D MC dose distributions were compared to measurements by Gafchromic EBT2
      films in the axial and coronal planes of the moving target object, and the
      coronal plane for the static off-target object based on the gamma metric at
      5%/3mm criteria (gamma5%/3mm). Treatment plans were considered acceptable if the
      percentage of pixels passing gamma5%/3mm (Pgamma<1) >= 90%. RESULTS: The averaged
      Pgamma<1 values of the 3D EPL, 3D MC, 4D EPL, and 4D MC dose calculation methods
      for the moving target plans are 95%, 95%, 94%, and 95% for reproducible motion,
      and 95%, 96%, 94%, and 93% for nonreproducible motion during actual treatment
      delivery. The overall measured target dose distributions are in better agreement
      with the 3DMC dose distributions than the 4DMC dose distributions. Conversely,
      measured dose distributions agree much better with the 4D EPL/MC than the 3D
      EPL/MC dose distributions in the static off-target structure, resulting in higher
      Pgamma<1 values with 4D EPL/MC (91%) vs 3D EPL (24%) and 3D MC (25%). Systematic
      changes of target motion reduced the averaged Pgamma<1 to 47% and 53% for 4D EPL
      and 4D MC dose calculations, and 22% for 3D EPL/MC dose calculations in the off
      target films. CONCLUSIONS: In robotic tracking SBRT, 4D treatment planning was
      found to yield better prediction of the dose distributions in the off-target
      structure, but not necessarily in the moving target, compared to standard 3D
      treatment planning, for reproducible and nonreproducible target motion. It is
      important to ensure on a patient-by-patient basis that the cumulative uncertainty
      associated with the 4D-CT artifacts, deformable image registration, and motion
      variability is significantly smaller than the cumulative uncertainty occurred in
      standard 3D planning in order to make 4D planning a justified option.

PMID- 23556883
TI  - Feasibility of producing a short, high energy s-band linear accelerator using a
      klystron power source.
AB  - PURPOSE: To use a finite-element method (FEM) model to study the feasibility of
      producing a short s-band (2.9985 GHz) waveguide capable of producing x-rays
      energies up to 10 MV, for applications in a linac-MR, as well as conventional
      radiotherapy. METHODS: An existing waveguide FEM model developed by the authors'
      group is used to simulate replacing the magnetron power source with a klystron.
      Peak fields within the waveguide are compared with a published experimental
      threshold for electric breakdown. The RF fields in the first accelerating cavity
      are scaled, approximating the effect of modifications to the first coupling
      cavity. Electron trajectories are calculated within the RF fields, and the energy
      spectrum, beam current, and focal spot of the electron beam are analyzed. One
      electron spectrum is selected for Monte Carlo simulations and the resulting PDD
      compared to measurement. RESULTS: When the first cavity fields are scaled by a
      factor of 0.475, the peak magnitude of the electric fields within the waveguide
      are calculated to be 223.1 MV/m, 29% lower than the published threshold for
      breakdown at this operating frequency. Maximum electron energy increased from 6.2
      to 10.4 MeV, and beam current increased from 134 to 170 mA. The focal spot FWHM
      is decreased slightly from 0.07 to 0.05 mm, and the width of the energy spectrum
      increased slightly from 0.44 to 0.70 MeV. Monte Carlo results show dmax is at
      2.15 cm for a 10 * 10 cm(2) field, compared with 2.3 cm for a Varian 10 MV linac,
      while the penumbral widths are 4.8 and 5.6 mm, respectively. CONCLUSIONS: The
      authors' simulation results show that a short, high-energy, s-band accelerator is
      feasible and electric breakdown is not expected to interfere with operation at
      these field strengths. With minor modifications to the first coupling cavity, all
      electron beam parameters are improved.

PMID- 23556884
TI  - Automatic patient alignment system using 3D ultrasound.
AB  - PURPOSE: Recent developments in radiation therapy such as intensity modulated
      radiotherapy (IMRT) or dose painting promise to provide better dose distribution
      on the tumor. For effective application of these methods the exact positioning of
      the patient and the localization of the irradiated organ and surrounding
      structures is crucial. Especially with respect to the treatment of the prostate,
      ultrasound (US) allows for differentiation between soft tissue and was therefore
      applied by various repositioning systems, such as BAT or Clarity. The authors
      built a new system which uses 3D US at both sites, the CT room and the
      intervention room and applied a 3D/3D US/US registration for automatic
      repositioning. METHODS: In a first step the authors applied image preprocessing
      methods to prepare the US images for an optimal registration process. For the
      3D/3D registration procedure five different metrics were evaluated. To find the
      image metric which fits best for a particular patient three 3D US images were
      taken at the CT site and registered to each other. From these results an US
      registration error was calculated. The most successful image metric was then
      applied for the US/US registration process. The success of the whole
      repositioning method was assessed by taking the results of an ExacTrac system as
      golden standard. RESULTS: The US/US registration error was found to be 2.99 +/-
      1.54 mm with respect to the mutual information metric by Mattes (eleven patients)
      which revealed to be the most suitable of the assessed metrics. For complete
      repositioning chain the error amounted to 4.15 +/- 1.20 mm (ten patients).
      CONCLUSIONS: The authors developed a system for patient repositioning which works
      automatically without the necessity of user interaction with an accuracy which
      seems to be suitable for clinical application.

PMID- 23556885
TI  - Loss of local control due to tumor displacement as a function of margin size,
      dose-response slope, and number of fractions.
AB  - PURPOSE: Geometric uncertainties are inevitable in radiotherapy. To account for
      these uncertainties, a margin is added to the clinical target volume (CTV) to
      create the planning target volume (PTV), and its size is critical for obtaining
      an optimal treatment plan. Dose-based (i.e., physical) margin recipes have been
      published and widely used, but it is important to consider fractionation and the
      radiobiological characteristics of the tumor when deriving margins. Hence a tumor
      control probability (TCP)-based margin is arguably more appropriate. METHODS:
      Margins required for <= 1% loss in mean population TCP (relative to a static
      tumor) for varying numbers of fractions, varying slope of the dose-response curve
      (gamma50) and varying degrees of dose distribution conformity are investigated
      for spherical and four-field (4F)-brick dose distributions. To simulate geometric
      uncertainties, systematic (Sigma) and random (sigma) tumor displacements were
      sampled from Gaussian distributions and applied to each fraction for a spherical
      CTV. Interfraction tumor motion was simulated and the dose accumulated from
      fraction to fraction on a voxel-by-voxel basis to calculate TCP. PTV margins
      derived from this work for various fraction numbers and dose-response slopes
      (gamma50) for different degrees of geometric uncertainties are compared with
      margins calculated using published physical-dose- and TCP-based recipes. RESULTS:
      Larger margins are required for a decrease in the number of fractions and for an
      increase in gamma50 for both spherical and 4F-brick dose distributions. However,
      the margins can be close to zero for the 4F-brick distribution for small
      geometric uncertainties (Sigma = 1, sigma = 1 mm) irrespective of the number of
      fractions and the magnitude of gamma50 due to the higher "incidental" dose
      outside the tumor. For Sigma = 1 mm and sigma = 3 mm, physical-dose-based recipes
      underestimate the margin only for the combination of hypofractionated treatments
      and tumors with a high gamma50. For all other situations TCP-based margins are
      smaller than physical-dose-based recipes. CONCLUSIONS: Margins depend on the
      number of fractions and gamma50 in addition to Sigma and sigma. Dose conformity
      should also be considered since the required margin increases with increasing
      dose conformity. Ideally margins should be anisotropic and individualized, taking
      into account gamma50, number of fractions, and the dose distribution, as well as
      estimates of Sigma and sigma. No single "recipe" can adequately account for all
      these variables.

PMID- 23556886
TI  - Modeling respiratory motion for reducing motion artifacts in 4D CT images.
AB  - PURPOSE: Four-dimensional computed tomography (4D CT) images have been recently
      adopted in radiation treatment planning for thoracic and abdominal cancers to
      explicitly define respiratory motion and anatomy deformation. However,
      significant image distortions (artifacts) exist in 4D CT images that may affect
      accurate tumor delineation and the shape representation of normal anatomy. In
      this study, the authors present a patient-specific respiratory motion model,
      based on principal component analysis (PCA) of motion vectors obtained from
      deformable image registration, with the main goal of reducing image artifacts
      caused by irregular motion during 4D CT acquisition. METHODS: For a 4D CT image
      set of a specific patient, the authors calculated displacement vector fields
      relative to a reference phase, using an in-house deformable image registration
      method. The authors then used PCA to decompose each of the displacement vector
      fields into linear combinations of principal motion bases. The authors have
      demonstrated that the regular respiratory motion of a patient can be accurately
      represented by a subspace spanned by three principal motion bases and their
      projections. These projections were parameterized using a spline model to allow
      the reconstruction of the displacement vector fields at any given phase in a
      respiratory cycle. Finally, the displacement vector fields were used to deform
      the reference CT image to synthesize CT images at the selected phase with much
      reduced image artifacts. RESULTS: The authors evaluated the performance of the in
      house deformable image registration method using benchmark datasets consisting of
      ten 4D CT sets annotated with 300 landmark pairs that were approved by
      physicians. The initial large discrepancies across the landmark pairs were
      significantly reduced after deformable registration, and the accuracy was similar
      to or better than that reported by state-of-the-art methods. The proposed motion
      model was quantitatively validated on 4D CT images of a phantom and a lung cancer
      patient by comparing the synthesized images and the original images at different
      phases. The synthesized images matched well with the original images. The motion
      model was used to reduce irregular motion artifacts in the 4D CT images of three
      lung cancer patients. Visual assessment indicated that the proposed approach
      could reduce severe image artifacts. The shape distortions around the diaphragm
      and tumor regions were mitigated in the synthesized 4D CT images. CONCLUSIONS:
      The authors have derived a mathematical model to represent the regular
      respiratory motion from a patient-specific 4D CT set and have demonstrated its
      application in reducing irregular motion artifacts in 4D CT images. The authors'
      approach can mitigate shape distortions of anatomy caused by irregular breathing
      motion during 4D CT acquisition.

PMID- 23556887
TI  - Investigation of gated cone-beam CT to reduce respiratory motion blurring.
AB  - PURPOSE: Methods of reducing respiratory motion blurring in cone-beam CT (CBCT)
      have been limited to lung where soft tissue contrast is large. Respiration
      correlated cone-beam CT uses slow continuous gantry rotation but image quality is
      limited by uneven projection spacing. This study investigates the efficacy of a
      novel gated CBCT technique. METHODS: In gated CBCT, the linac is programmed such
      that gantry rotation and kV image acquisition occur within a gate around end
      expiration and are triggered by an external respiratory monitor. Standard CBCT
      and gated CBCT scans are performed in 22 patients (11 thoracic, 11 abdominal) and
      a respiration-correlated CT (RCCT) scan, acquired on a standard CT scanner, from
      the same day serves as a criterion standard. Image quality is compared by
      calculating contrast-to-noise ratios (CNR) for tumors in lung, gastroesophageal
      junction (GEJ) tissue, and pancreas tissue, relative to surrounding background
      tissue. Congruence between the object in the CBCT images and that in the RCCT is
      measured by calculating the optimized normalized cross-correlation (NCC)
      following CBCT-to-RCCT rigid registrations. RESULTS: Gated CBCT results in
      reduced motion artifacts relative to standard CBCT, with better visualization of
      tumors in lung, and of abdominal organs including GEJ, pancreas, and organs at
      risk. CNR of lung tumors is larger in gated CBCT in 6 of 11 cases relative to
      standard CBCT. A paired two-tailed t-test of lung patient mean CNR shows no
      statistical significance (p = 0.133). In 4 of 5 cases where CNR is not increased,
      lung tumor motion observed in RCCT is small (range 1.3-5.2 mm). CNR is increased
      and becomes statistically significant for 6 out of 7 lung patients with > 5 mm
      tumor motion (p = 0.044). CNR is larger in gated CBCT in 5 of 7 GEJ cases and 3
      of 4 pancreas cases (p = 0.082 and 0.192). Gated CBCT yields improvement with
      lower NCC relative to standard CBCT in 10 of 11, 7 of 7, and 3 of 4 patients for
      lung, GEJ, and pancreas images, respectively (p = 0.0014, 0.0030, 0.165).
      CONCLUSIONS: Gated CBCT reduces image blurring caused by respiratory motion. The
      gated gantry rotation yields uniformly and closely spaced projections resulting
      in improved reconstructed image quality. The technique is shown to be applicable
      to abdominal sites, where image contrast of soft tissues is low.

PMID- 23556888
TI  - Geometrical splitting technique to improve the computational efficiency in Monte
      Carlo calculations for proton therapy.
AB  - PURPOSE: To present the implementation and validation of a geometrical based
      variance reduction technique for the calculation of phase space data for proton
      therapy dose calculation. METHODS: The treatment heads at the Francis H Burr
      Proton Therapy Center were modeled with a new Monte Carlo tool (TOPAS based on
      Geant4). For variance reduction purposes, two particle-splitting planes were
      implemented. First, the particles were split upstream of the second scatterer or
      at the second ionization chamber. Then, particles reaching another plane
      immediately upstream of the field specific aperture were split again. In each
      case, particles were split by a factor of 8. At the second ionization chamber and
      at the latter plane, the cylindrical symmetry of the proton beam was exploited to
      position the split particles at randomly spaced locations rotated around the beam
      axis. Phase space data in IAEA format were recorded at the treatment head exit
      and the computational efficiency was calculated. Depth-dose curves and beam
      profiles were analyzed. Dose distributions were compared for a voxelized water
      phantom for different treatment fields for both the reference and optimized
      simulations. In addition, dose in two patients was simulated with and without
      particle splitting to compare the efficiency and accuracy of the technique.
      RESULTS: A normalized computational efficiency gain of a factor of 10-20.3 was
      reached for phase space calculations for the different treatment head options
      simulated. Depth-dose curves and beam profiles were in reasonable agreement with
      the simulation done without splitting: within 1% for depth-dose with an average
      difference of (0.2 +/- 0.4)%, 1 standard deviation, and a 0.3% statistical
      uncertainty of the simulations in the high dose region; 1.6% for planar fluence
      with an average difference of (0.4 +/- 0.5)% and a statistical uncertainty of
      0.3% in the high fluence region. The percentage differences between dose
      distributions in water for simulations done with and without particle splitting
      were within the accepted clinical tolerance of 2%, with a 0.4% statistical
      uncertainty. For the two patient geometries considered, head and prostate, the
      efficiency gain was 20.9 and 14.7, respectively, with the percentages of voxels
      with gamma indices lower than unity 98.9% and 99.7%, respectively, using 2% and 2
      mm criteria. CONCLUSIONS: The authors have implemented an efficient variance
      reduction technique with significant speed improvements for proton Monte Carlo
      simulations. The method can be transferred to other codes and other treatment
      heads.

PMID- 23556889
TI  - Patterns of patient specific dosimetry in total body irradiation.
AB  - PURPOSE: Total body irradiation (TBI) has been used for bone marrow transplant
      for hematologic and immune deficiency conditions. The goal of TBI is to deliver a
      homogeneous dose to the entire body, with a generally accepted range of dose
      uniformity being within +/- 10% of the prescribed dose. The moving table
      technique for TBI could make dose uniform in whole body by adjusting couch speed.
      However, it is difficult to accurately estimate the actual dose by calculation
      and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors
      present patterns of patient-specific IVD in 161 TBI patients treated at our
      institution. METHODS: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy
      unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial
      Products, Inc., Fishers, IN) were used for TBI treatment. During treatment,
      OneDose(TM) (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect
      Transistor detectors were placed at patient body surface; both entrance and exit
      side of the beam at patient head, neck, mediastinum, umbilicus, and knee to
      estimate midplane dose. When large differences (>10%) between the prescribed and
      measured dose were observed, dose delivery was corrected for subsequent fractions
      by the adjustment of couch speed and/or bolus placement. Under IRB exempt status,
      the authors retrospectively analyzed the treatment records of 161 patients who
      received TBI treatment between 2006 and 2011. RESULTS: Across the entire cohort,
      the median +/- SD (range) percent variance between calculated and measured dose
      for head, neck, mediastinum, umbilicus, and knee was -2.3 +/- 10.2% (-66.2 to
      +35.3), 1.1 +/- 11.5% (-62.2 to +40.3), -1.9 +/- 9.5% (-66.4 to +46.6), -1.1 +/-
      7.2% (-35.2 to +42.9), and 3.4 +/- 12.2% (-47.9 to +108.5), respectively. More
      than half of treatments were within +/- 10% of the prescribed dose for all
      anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was
      within +/- 10%. However, some large differences greater than 35% were also found
      at several points. For one case, the knee received double the prescribed dose.
      When the dose differences for multiple fractions were averaged, compliance (+/- 1
      0%) between the prescription and measured dose was improved compared to the dose
      difference of the first single fraction, for example, as at umbilicus, which
      improved from 83.9% to 98.5%. CONCLUSIONS: Actual dose measurement analysis of
      TBI patients revealed a potentially wide variance from the calculated dose. Based
      from their IVD method for TBI using Cobalt-60 irradiator and moving table, +/-
      10% over entire body is hard to achieve. However, it can be significantly
      improved with immediate feedback after the first fraction prior to subsequent
      treatments.

PMID- 23556890
TI  - A novel approach in electron beam radiation therapy of lips carcinoma: a Monte
      Carlo study.
AB  - PURPOSE: Squamous cell carcinoma (SCC) is commonly treated by electron beam
      radiotherapy (EBRT) followed by a boost via brachytherapy. Considering the
      limitations associated with brachytherapy, in this study, a novel boosting
      technique in EBRT of lip carcinoma using an internal shield as an internal dose
      enhancer tool (IDET) was evaluated. An IDET is referred to a partially covered
      internal shield located behind the lip. It was intended to show that while the
      backscattered electrons are absorbed in the portion covered with a low atomic
      number material, they will enhance the target dose in the uncovered area.
      METHODS: Monte-Carlo models of 6 and 8 MeV electron beams were developed using
      BEAMnrc code and were validated against experimental measurements. Using the
      developed models, dose distributions in a lip phantom were calculated and the
      effect of an IDET on target dose enhancement was evaluated. Typical lip
      thicknesses of 1.5 and 2.0 cm were considered. A 5 * 5 cm(2) of lead covered by
      0.5 cm of polystyrene was used as an internal shield, while a 4 * 4 cm(2)
      uncovered area of the shield was used as the dose enhancer. RESULTS: Using the
      IDET, the maximum dose enhancement as a percentage of dose at dmax of the
      unshielded field was 157.6% and 136.1% for 6 and 8 MeV beams, respectively. The
      best outcome was achieved for lip thickness of 1.5 cm and target thickness of
      less than 0.8 cm. For lateral dose coverage of planning target volume, the 80%
      isodose curve at the lip-IDET interface showed a 1.2 cm expansion, compared to
      the unshielded field. CONCLUSIONS: This study showed that a boost concomitant
      EBRT of lip is possible by modifying an internal shield into an IDET. This
      boosting method is especially applicable to cases in which brachytherapy faces
      limitations, such as small thicknesses of lips and targets located at the buccal
      surface of the lip.

PMID- 23556891
TI  - Development of a fast and feasible spectrum modeling technique for flattening
      filter free beams.
AB  - PURPOSE: To develop a fast and robust technique for the determination of
      optimized photon spectra for flattening filter free (FFF) beams to be applied in
      convolution/superposition dose calculations. METHODS: A two-step optimization
      method was developed to derive optimal photon spectra for FFF beams. In the first
      step, a simple functional form of the photon spectra proposed by Ali ["Functional
      forms for photon spectra of clinical linacs," Phys. Med. Biol. 57, 31-50 (2011)]
      is used to determine generalized shapes of the photon spectra. In this method,
      the photon spectra were defined for the ranges of field sizes to consider the
      variations of the contributions of scattered photons with field size. Percent
      depth doses (PDDs) for each field size were measured and calculated to define a
      cost function, and a collapsed cone convolution (CCC) algorithm was used to
      calculate the PDDs. In the second step, the generalized functional form of the
      photon spectra was fine-tuned in a process whereby the weights of photon fluence
      became the optimizing free parameters. A line search method was used for the
      optimization and first order derivatives with respect to the optimizing
      parameters were derived from the CCC algorithm to enhance the speed of the
      optimization. The derived photon spectra were evaluated, and the dose
      distributions using the optimized spectra were validated. RESULTS: The optimal
      spectra demonstrate small variations with field size for the 6 MV FFF beam and
      relatively large variations for the 10 MV FFF beam. The mean energies of the
      optimized 6 MV FFF spectra were decreased from 1.31 MeV for a 3 * 3 cm(2) field
      to 1.21 MeV for a 40 * 40 cm(2) field, and from 2.33 MeV at 3 * 3 cm(2) to 2.18
      MeV at 40 * 40 cm(2) for the 10 MV FFF beam. The developed method could
      significantly improve the agreement between the calculated and measured PDDs.
      Root mean square differences on the optimized PDDs were observed to be 0.41% (3 *
      3 cm(2)) down to 0.21% (40 * 40 cm(2)) for the 6 MV FFF beam, and 0.35% (3 * 3
      cm(2)) down to 0.29% (40 * 40 cm(2)) for the 10 MV FFF beam. The first order
      derivatives from the functional form were found to improve the speed of
      computational time up to 20 times compared to the other techniques. CONCLUSIONS:
      The derived photon spectra resulted in good agreements with measured PDDs over
      the range of field sizes investigated. The suggested method is easily applicable
      to commercial radiation treatment planning systems since it only requires
      measured PDDs as input.

PMID- 23556892
TI  - Dosimetric and geometric evaluation of a novel stereotactic radiotherapy device
      for breast cancer: the GammaPodTM.
AB  - PURPOSE: A dedicated stereotactic gamma irradiation device, the GammaPodTM from
      Xcision Medical Systems, was developed specifically to treat small breast
      cancers. This study presents the first evaluation of dosimetric and geometric
      characteristics from the initial prototype installed at University of Maryland
      Radiation Oncology Department. METHODS: The GammaPodTM stereotactic radiotherapy
      device is an assembly of a hemi-spherical source carrier containing 36 (60)Co
      sources, a tungsten collimator, a dynamically controlled patient support table,
      and the breast immobilization system which also functions as a stereotactic
      frame. The source carrier contains the sources in six columns spaced
      longitudinally at 60 degrees  intervals and it rotates together with the variable
      size collimator to form 36 noncoplanar, concentric arcs focused at the isocenter.
      The patient support table enables motion in three dimensions to position the
      patient tumor at the focal point of the irradiation. The table moves continuously
      in three cardinal dimensions during treatment to provide dynamic shaping of the
      dose distribution. The breast is immobilized using a breast cup applying a small
      negative pressure, where the immobilization cup is embedded with fiducials also
      functioning as the stereotactic frame for the breast. Geometric and dosimetric
      evaluations of the system as well as a protocol for absorbed dose calibration are
      provided. Dosimetric verifications of dynamically delivered patient plans are
      performed for seven patients using radiochromic films in hypothetical preop,
      postop, and target-in-target treatment scenarios. RESULTS: Loaded with 36 (60)Co
      sources with cumulative activity of 4320 Ci, the prototype GammaPodTM unit
      delivers 5.31 Gy/min at the isocenter using the largest 2.5 cm diameter
      collimator. Due to the noncoplanar beam arrangement and dynamic dose shaping
      features, the GammaPodTM device is found to deliver uniform doses to targets with
      good conformity. The spatial accuracy of the device to locate the radiation
      isocenter is determined to be less than 1 mm. Single shot profiles with 2.5 cm
      collimator are measured with radiochromic film and found to be in good agreement
      with respect to the Monte Carlo based calculations (congruence of FWHM less than
      1 mm). Dosimetric verifications corresponding to all hypothetical treatment plans
      corresponding to three target scenarios for each of the seven patients
      demonstrated good agreement with gamma index pass rates of better than 97% (99.0%
      +/- 0.7%). CONCLUSIONS: Dosimetric evaluation of the first GammaPodTM
      stereotactic breast radiotherapy unit was performed and the dosimetric and
      spatial accuracy of this novel technology is found to be feasible with respect to
      clinical radiotherapy standards. The observed level of agreement between the
      treatment planning system calculations and dosimetric measurements has confirmed
      that the system can deliver highly complex treatment plans with remarkable
      geometric and dosimetric accuracy.

PMID- 23556893
TI  - Commissioning dose computation models for spot scanning proton beams in water for
      a commercially available treatment planning system.
AB  - PURPOSE: To present our method and experience in commissioning dose models in
      water for spot scanning proton therapy in a commercial treatment planning system
      (TPS). METHODS: The input data required by the TPS included in-air transverse
      profiles and integral depth doses (IDDs). All input data were obtained from Monte
      Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs
      were converted to units of Gy mm(2)/MU using the measured IDDs at a depth of 2 cm
      employing the largest commercially available parallel-plate ionization chamber.
      The sensitive area of the chamber was insufficient to fully encompass the entire
      lateral dose deposited at depth by a pencil beam (spot). To correct for the
      detector size, correction factors as a function of proton energy were defined and
      determined using MC. The fluence of individual spots was initially modeled as a
      single Gaussian (SG) function and later as a double Gaussian (DG) function. The
      DG fluence model was introduced to account for the spot fluence due to
      contributions of large angle scattering from the devices within the scanning
      nozzle, especially from the spot profile monitor. To validate the DG fluence
      model, we compared calculations and measurements, including doses at the center
      of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and
      SOBP width, lateral dose profiles, and depth doses for different widths of SOBP.
      Dose models were validated extensively with patient treatment field-specific
      measurements. RESULTS: We demonstrated that the DG fluence model is necessary for
      predicting the field size dependence of dose distributions. With this model, the
      calculated doses at the center of SOBPs as a function of nominal field size,
      range, and SOBP width, lateral dose profiles and depth doses for rectangular
      target volumes agreed well with respective measured values. With the DG fluence
      model for our scanning proton beam line, we successfully treated more than 500
      patients from March 2010 through June 2012 with acceptable agreement between TPS
      calculated and measured dose distributions. However, the current dose model still
      has limitations in predicting field size dependence of doses at some intermediate
      depths of proton beams with high energies. CONCLUSIONS: We have commissioned a DG
      fluence model for clinical use. It is demonstrated that the DG fluence model is
      significantly more accurate than the SG fluence model. However, some deficiencies
      in modeling the low-dose envelope in the current dose algorithm still exist.
      Further improvements to the current dose algorithm are needed. The method
      presented here should be useful for commissioning pencil beam dose algorithms in
      new versions of TPS in the future.

PMID- 23556894
TI  - Evaluation of plastic materials for range shifting, range compensation, and solid
      phantom dosimetry in carbon-ion radiotherapy.
AB  - PURPOSE: Beam range control is the essence of radiotherapy with heavy charged
      particles. In conventional broad-beam delivery, fine range adjustment is achieved
      by insertion of range shifting and compensating materials. In dosimetry, solid
      phantoms are often used for convenience. These materials should ideally be
      equivalent to water. In this study, the authors evaluated dosimetric water
      equivalence of four common plastics, high-density polyethylene (HDPE), polymethyl
      methacrylate (PMMA), polyethylene terephthalate (PET), and polyoxymethylene
      (POM). METHODS: Using the Bethe formula for energy loss, the Gottschalk formula
      for multiple scattering, and the Sihver formula for nuclear interactions, the
      authors calculated the effective densities of the plastics for these
      interactions. The authors experimentally measured variation of the Bragg peak of
      carbon-ion beams by insertion of HDPE, PMMA, and POM, which were compared with
      analytical model calculations. RESULTS: The theoretical calculation resulted in
      slightly reduced multiple scattering and severely increased nuclear interactions
      for HDPE, compared to water and the other plastics. The increase in attenuation
      of carbon ions for 20-cm range shift was experimentally measured to be 8.9% for
      HDPE, 2.5% for PMMA, and 0.0% for POM while PET was theoretically estimated to be
      in between PMMA and POM. The agreement between the measurements and the
      calculations was about 1% or better. CONCLUSIONS: For carbon-ion beams, POM was
      dosimetrically indistinguishable from water and the best of the plastics examined
      in this study. The poorest was HDPE, which would reduce the Bragg peak by 0.45%
      per cm range shift, although with marginal superiority for reduced multiple
      scattering. Between the two clear plastics, PET would be superior to PMMA in
      dosimetric water equivalence.

PMID- 23556895
TI  - Respiratory triggered 4D cone-beam computed tomography: a novel method to reduce
      imaging dose.
AB  - PURPOSE: A novel method called respiratory triggered 4D cone-beam computed
      tomography (RT 4D CBCT) is described whereby imaging dose can be reduced without
      degrading image quality. RT 4D CBCT utilizes a respiratory signal to trigger
      projections such that only a single projection is assigned to a given respiratory
      bin for each breathing cycle. In contrast, commercial 4D CBCT does not actively
      use the respiratory signal to minimize image dose. METHODS: To compare RT 4D CBCT
      with conventional 4D CBCT, 3600 CBCT projections of a thorax phantom were
      gathered and reconstructed to generate a ground truth CBCT dataset. Simulation
      pairs of conventional 4D CBCT acquisitions and RT 4D CBCT acquisitions were
      developed assuming a sinusoidal respiratory signal which governs the selection of
      projections from the pool of 3600 original projections. The RT 4D CBCT
      acquisition triggers a single projection when the respiratory signal enters a
      desired acquisition bin; the conventional acquisition does not use a respiratory
      trigger and projections are acquired at a constant frequency. Acquisition
      parameters studied were breathing period, acquisition time, and imager frequency.
      The performance of RT 4D CBCT using phase based and displacement based sorting
      was also studied. Image quality was quantified by calculating difference images
      of the test dataset from the ground truth dataset. Imaging dose was calculated by
      counting projections. RESULTS: Using phase based sorting RT 4D CBCT results in
      47% less imaging dose on average compared to conventional 4D CBCT. Image quality
      differences were less than 4% at worst. Using displacement based sorting RT 4D
      CBCT results in 57% less imaging dose on average, than conventional 4D CBCT
      methods; however, image quality was 26% worse with RT 4D CBCT. CONCLUSIONS:
      Simulation studies have shown that RT 4D CBCT reduces imaging dose while
      maintaining comparable image quality for phase based 4D CBCT; image quality is
      degraded for displacement based RT 4D CBCT in its current implementation.

PMID- 23556896
TI  - Mass detection in reconstructed digital breast tomosynthesis volumes with a
      computer-aided detection system trained on 2D mammograms.
AB  - PURPOSE: To develop a computer-aided detection (CAD) system for masses in digital
      breast tomosynthesis (DBT) which can make use of an existing CAD system for
      detection of breast masses in full-field digital mammography (FFDM). This
      approach has the advantage that large digital screening databases that are
      becoming available can be used for training. DBT is currently not used for
      screening which makes it hard to obtain sufficient data for training. METHODS:
      The proposed CAD system is applied to reconstructed DBT volumes and consists of
      two stages. In the first stage, an existing 2D CAD system is applied to slabs
      composed of multiple DBT slices, after processing the slabs to a representation
      similar to that of the FFDM training data. In the second stage, the authors group
      detections obtained in the slabs that detect the same object and determine the 3D
      location of the grouped findings using one of three different approaches,
      including one that uses a set of features extracted from the DBT slabs.
      Experiments were conducted to determine performance of the CAD system, the
      optimal slab thickness for this approach and the best method to establish the 3D
      location. Experiments were performed using a database of 192 patients (752 DBT
      volumes). In 49 patients, one or more malignancies were present which were
      described as a mass, architectural distortion, or asymmetry. Free response
      receiver operating characteristic analysis and bootstrapping were used for
      statistical evaluation. RESULTS: Best performance was obtained when slab
      thickness was in the range of 1-2 cm. Using the feature based 3D localization
      procedure developed in the study, accurate 3D localization could be obtained in
      most cases. Case sensitivities of 80% and 90% were achieved at 0.35 and 0.99
      false positives per volume, respectively. CONCLUSIONS: This study indicates that
      there may be a large benefit in using 2D mammograms for the development of CAD
      for DBT and that there is no need to exclusively limit development to DBT data.

PMID- 23556897
TI  - The feasibility of head motion tracking in helical CT: a step toward motion
      correction.
AB  - PURPOSE: To establish a practical and accurate motion tracking method for the
      development of rigid motion correction methods in helical x-ray computed
      tomography (CT). METHODS: A commercially available optical motion tracking system
      provided 6 degrees of freedom pose measurements at 60 Hz. A 4 * 4 calibration
      matrix was determined to convert raw pose data acquired in tracker coordinates to
      a fixed CT coordinate system with origin at the isocenter of the scanner. Two
      calibration methods, absolute orientation (AO), and a new method based on image
      registration (IR), were compared by means of landmark analysis and correlation
      coefficient in phantom images coregistered using the derived motion
      transformations. RESULTS: Transformations calculated using the IR-derived
      calibration matrix were found to be more accurate, with positional errors less
      than 0.5 mm (mean RMS), and highly correlated image voxel intensities. The AO
      derived calibration matrix yielded larger mean RMS positional errors (~ 1.0 mm),
      and poorer correlation coefficients. CONCLUSIONS: The authors have demonstrated
      the feasibility of accurate motion tracking for retrospective motion correction
      in helical CT. Their new IR-based calibration method based on image registration
      and function minimization was simpler to perform and delivered more accurate
      calibration matrices. This technique is a useful tool for future work on rigid
      motion correction in helical CT and potentially also other imaging modalities.

PMID- 23556898
TI  - Optical photon transport in powdered-phosphor scintillators. Part 1. Multiple
      scattering and validity of the Boltzmann transport equation.
AB  - PURPOSE: In Part 1 of this two-part work, predictions for light transport in
      powdered-phosphor screens are made, based on three distinct approaches.
      Predictions of geometrical optics-based ray tracing through an explicit
      microscopic model (EMM) for screen structure are compared to a Monte Carlo
      program based on the Boltzmann transport equation (BTE) and Swank's diffusion
      equation solution. The purpose is to: (I) highlight the additional assumptions of
      the BTE Monte Carlo method and Swank's model (both previously used in the
      literature) with respect to the EMM approach; (II) demonstrate the equivalences
      of the approaches under well-defined conditions and; (III) identify the onset and
      severity of any discrepancies between the models. A package of computer code
      (called phsphr) is supplied which can be used to reproduce the BTE Monte Carlo
      results presented in this work. METHODS: The EMM geometrical optics ray-tracing
      model is implemented for hypothesized microstructures of phosphor grains in a
      binder. The BTE model is implemented as a Monte Carlo program with transport
      parameters, derived from geometrical optics, as inputs. The analytical solution
      of Swank to the diffusion equation is compared to the EMM and BTE predictions.
      Absorbed fractions and MTFs are calculated for a range of binder-to-phosphor
      relative refractive indices (n = 1.1-5.0), screen thicknesses (t = 50-200 MUm),
      and packing fill factors (pf = 0.04-0.54). RESULTS: Disagreement between the BTE
      and EMM approaches increased with n and pf. For the largest relative refractive
      index (n = 5) and highest packing fill (pf = 0.5), the BTE model underestimated
      the absorbed fraction and MTF50, by up to 40% and 20%, respectively. However, for
      relative refractive indices typical of real phosphor screens (n <= 2), such as
      Gd2O2S:Tb, the BTE and EMM predictions agreed well at all simulated packing
      densities. In addition, Swank's model agreed closely with the BTE predictions
      when the screen was thick enough to be considered turbid. CONCLUSIONS: Although
      some assumptions of the BTE are violated in realistic powdered-phosphor screens,
      these appear to lead to negligible effects in the modeling of optical transport
      for typical phosphor and binder refractive indices. Therefore it is reasonable to
      use Monte Carlo codes based on the BTE to treat this problem. Furthermore,
      Swank's diffusion equation solution is an adequate approximation if a turbidity
      condition, presented here, is satisfied.

PMID- 23556899
TI  - Optical photon transport in powdered-phosphor scintillators. Part II. Calculation
      of single-scattering transport parameters.
AB  - PURPOSE: Monte Carlo methods based on the Boltzmann transport equation (BTE) have
      previously been used to model light transport in powdered-phosphor scintillator
      screens. Physically motivated guesses or, alternatively, the complexities of Mie
      theory have been used by some authors to provide the necessary inputs of
      transport parameters. The purpose of Part II of this work is to: (i) validate
      predictions of modulation transform function (MTF) using the BTE and calculated
      values of transport parameters, against experimental data published for two
      Gd2O2S:Tb screens; (ii) investigate the impact of size-distribution and emission
      spectrum on Mie predictions of transport parameters; (iii) suggest simpler and
      novel geometrical optics-based models for these parameters and compare to the
      predictions of Mie theory. A computer code package called phsphr is made
      available that allows the MTF predictions for the screens modeled to be
      reproduced and novel screens to be simulated. METHODS: The transport parameters
      of interest are the scattering efficiency (Q sct), absorption efficiency (Q abs),
      and the scatter anisotropy (g). Calculations of these parameters are made using
      the analytic method of Mie theory, for spherical grains of radii 0.1-5.0 MUm. The
      sensitivity of the transport parameters to emission wavelength is investigated
      using an emission spectrum representative of that of Gd2O2S:Tb. The impact of a
      grain-size distribution in the screen on the parameters is investigated using a
      Gaussian size-distribution (sigma = 1%, 5%, or 10% of mean radius). Two simple
      and novel alternative models to Mie theory are suggested: a geometrical optics
      and diffraction model (GODM) and an extension of this (GODM+). Comparisons to
      measured MTF are made for two commercial screens: Lanex Fast Back and Lanex Fast
      Front (Eastman Kodak Company, Inc.). RESULTS: The Mie theory predictions of
      transport parameters were shown to be highly sensitive to both grain size and
      emission wavelength. For a phosphor screen structure with a distribution in grain
      sizes and a spectrum of emission, only the average trend of Mie theory is likely
      to be important. This average behavior is well predicted by the more
      sophisticated of the geometrical optics models (GODM+) and in approximate
      agreement for the simplest (GODM). The root-mean-square differences obtained
      between predicted MTF and experimental measurements, using all three models
      (GODM, GODM+, Mie), were within 0.03 for both Lanex screens in all cases. This is
      excellent agreement in view of the uncertainties in screen composition and
      optical properties. CONCLUSIONS: If Mie theory is used for calculating transport
      parameters for light scattering and absorption in powdered-phosphor screens, care
      should be taken to average out the fine-structure in the parameter predictions.
      However, for visible emission wavelengths (lambda < 1.0 MUm) and grain radii (a >
      0.5 MUm), geometrical optics models for transport parameters are an alternative
      to Mie theory. These geometrical optics models are simpler and lead to no
      substantial loss in accuracy.

PMID- 23556900
TI  - X-ray phase contrast imaging of the breast: analysis of tissue simulating
      materials.
AB  - PURPOSE: Phase contrast imaging, particularly of the breast, is being actively
      investigated. The purpose of this work is to investigate the x-ray phase contrast
      properties of breast tissues and commonly used breast tissue substitutes or
      phantom materials with an aim of determining the phantom materials best
      representative of breast tissues. METHODS: Elemental compositions of breast
      tissues including adipose, fibroglandular, and skin were used to determine the
      refractive index, n = 1 - delta + i beta. The real part of the refractive index,
      specifically the refractive index decrement (delta), over the energy range of 5
      50 keV were determined using XOP software (version 2.3, European Synchrotron
      Radiation Facility, France). Calcium oxalate and calcium hydroxyapatite were
      considered to represent the material compositions of microcalcifications in vivo.
      Nineteen tissue substitutes were considered as possible candidates to represent
      adipose tissue, fibroglandular tissue and skin, and four phantom materials were
      considered as possible candidates to represent microcalcifications. For each
      material, either the molecular formula, if available, or the elemental
      composition based on weight fraction, was used to determine delta. At each x-ray
      photon energy, the absolute percent difference in delta between the breast tissue
      and the substitute material was determined, from which three candidates were
      selected. From these candidate tissue substitutes, the material that minimized
      the absolute percent difference in linear attenuation coefficient MU, and hence
      beta, was considered to be best representative of that breast tissue. RESULTS:
      Over the energy range of 5-50 keV, while the delta of CB3 and fibroglandular
      tissue-equivalent material were within 1% of that of fibroglandular tissue, the
      MU of fibroglandular tissue-equivalent material better approximated the
      fibroglandular tissue. While the delta of BR10 and adipose tissue-equivalent
      material were within 1% of that of adipose tissue, the tissue-equivalent material
      better approximated the adipose tissue in terms of MU. Polymethyl methacrylate, a
      commonly used tissue substitute, exhibited delta greater than fibroglandular
      tissue by ~ 12%. The A-150 plastic closely approximated the skin. Several
      materials exhibited delta between that of adipose and fibroglandular tissue.
      However, there was an energy-dependent mismatch in terms of equivalent
      fibroglandular weight fraction between delta and MU for these materials. For
      microcalcifications, aluminum and calcium carbonate were observed to straddle the
      delta and MU of calcium oxalate and calcium hydroxyapatite. Aluminum oxide,
      commonly used to represent microcalcifications in the American College of
      Radiology recommended phantoms for accreditation exhibited delta greater than
      calcium hydroxyapatite by ~ 23%. CONCLUSIONS: A breast phantom comprising A-150
      plastic to represent the skin, commercially available adipose and fibroglandular
      tissue-equivalent formulations to represent adipose and fibroglandular tissue,
      respectively, was found to be best suited for x-ray phase-sensitive imaging of
      the breast. Calcium carbonate or aluminum can be used to represent
      microcalcifications.

PMID- 23556901
TI  - A method to measure paddle and detector pressures and footprints in mammography.
AB  - PURPOSE: Compression is necessary in mammography to improve image quality and
      reduce radiation burden. Maximizing the amount of breast in contact with the
      image receptor (IR) is important. To achieve this, for the craniocaudal
      projection, there is no consensus within the literature regarding how the IR
      should be positioned relative to the inframammary fold (IMF). No information
      exists within the literature to describe how pressure balancing between IR and
      paddle, and IR breast footprint, might be optimized. This paper describes a novel
      method for measuring the respective pressures applied to the breast from the IR
      and the paddle and a method to simultaneously measure the breast footprints on
      the IR and the paddle. METHODS: Using a deformable breast phantom and electronic
      pressure-sensitive mat, area and pressure readings were gathered from two
      mammography machines and four paddles at 60, 80, and 100 N with the IR positioned
      at -2, -1, 0, +1, and +2 cm relative to the IMF (60 combinations in total).
      RESULTS: Paddle and IR footprints were calculated along with a uniformity index
      (UI). For all four paddle/machine/pressure combinations the greatest IR footprint
      was achieved at IMF +2 cm. The UI indicates that the best pressure/footprint
      balance is achieved at IMF +1 cm. CONCLUSIONS: The authors' method appears to be
      suited to measuring breast footprints and pressures on IR and paddle and a human
      female study is planned.

PMID- 23556902
TI  - Prediction of human observer performance in a 2-alternative forced choice low
      contrast detection task using channelized Hotelling observer: impact of radiation
      dose and reconstruction algorithms.
AB  - PURPOSE: Efficient optimization of CT protocols demands a quantitative approach
      to predicting human observer performance on specific tasks at various scan and
      reconstruction settings. The goal of this work was to investigate how well a
      channelized Hotelling observer (CHO) can predict human observer performance on 2
      alternative forced choice (2AFC) lesion-detection tasks at various dose levels
      and two different reconstruction algorithms: a filtered-backprojection (FBP) and
      an iterative reconstruction (IR) method. METHODS: A 35 * 26 cm(2) torso-shaped
      phantom filled with water was used to simulate an average-sized patient. Three
      rods with different diameters (small: 3 mm; medium: 5 mm; large: 9 mm) were
      placed in the center region of the phantom to simulate small, medium, and large
      lesions. The contrast relative to background was -15 HU at 120 kV. The phantom
      was scanned 100 times using automatic exposure control each at 60, 120, 240, 360,
      and 480 quality reference mAs on a 128-slice scanner. After removing the three
      rods, the water phantom was again scanned 100 times to provide signal-absent
      background images at the exact same locations. By extracting regions of interest
      around the three rods and on the signal-absent images, the authors generated 21
      2AFC studies. Each 2AFC study had 100 trials, with each trial consisting of a
      signal-present image and a signal-absent image side-by-side in randomized order.
      In total, 2100 trials were presented to both the model and human observers. Four
      medical physicists acted as human observers. For the model observer, the authors
      used a CHO with Gabor channels, which involves six channel passbands, five
      orientations, and two phases, leading to a total of 60 channels. The performance
      predicted by the CHO was compared with that obtained by four medical physicists
      at each 2AFC study. RESULTS: The human and model observers were highly correlated
      at each dose level for each lesion size for both FBP and IR. The Pearson's
      product-moment correlation coefficients were 0.986 [95% confidence interval (CI):
      0.958-0.996] for FBP and 0.985 (95% CI: 0.863-0.998) for IR. Bland-Altman plots
      showed excellent agreement for all dose levels and lesions sizes with a mean
      absolute difference of 1.0% +/- 1.1% for FBP and 2.1% +/- 3.3% for IR.
      CONCLUSIONS: Human observer performance on a 2AFC lesion detection task in CT
      with a uniform background can be accurately predicted by a CHO model observer at
      different radiation dose levels and for both FBP and IR methods.

PMID- 23556903
TI  - High spatiotemporal resolution measurement of regional lung air volumes from 2D
      phase contrast x-ray images.
AB  - PURPOSE: Described herein is a new technique for measuring regional lung air
      volumes from two-dimensional propagation-based phase contrast x-ray (PBI) images
      at very high spatial and temporal resolution. Phase contrast dramatically
      increases lung visibility and the outlined volumetric reconstruction technique
      quantifies dynamic changes in respiratory function. These methods can be used for
      assessing pulmonary disease and injury and for optimizing mechanical ventilation
      techniques for preterm infants using animal models. METHODS: The volumetric
      reconstruction combines the algorithms of temporal subtraction and single image
      phase retrieval (SIPR) to isolate the image of the lungs from the thoracic cage
      in order to measure regional lung air volumes. The SIPR algorithm was used to
      recover the change in projected thickness of the lungs on a pixel-by-pixel basis
      (pixel dimensions ~ 16.2 MUm). The technique has been validated using numerical
      simulation and compared results of measuring regional lung air volumes with and
      without the use of temporal subtraction for removing the thoracic cage. To test
      this approach, a series of PBI images of newborn rabbit pups mechanically
      ventilated at different frequencies was employed. RESULTS: Regional lung air
      volumes measured from PBI images of newborn rabbit pups showed on average an
      improvement of at least 20% in 16% of pixels within the lungs in comparison to
      that measured without the use of temporal subtraction. The majority of pixels
      that showed an improvement was found to be in regions occupied by bone. Applying
      the volumetric technique to sequences of PBI images of newborn rabbit pups, it is
      shown that lung aeration at birth can be highly heterogeneous. CONCLUSIONS: This
      paper presents an image segmentation technique based on temporal subtraction that
      has successfully been used to isolate the lungs from PBI chest images, allowing
      the change in lung air volume to be measured over regions as small as the pixel
      size. Using this technique, it is possible to measure changes in regional lung
      volume at high spatial and temporal resolution during breathing at much lower x
      ray dose than would be required using computed tomography.

PMID- 23556904
TI  - A hybrid metal artifact reduction algorithm for x-ray CT.
AB  - PURPOSE: Presence of metal artifacts is a major reason of degradation of computed
      tomography image quality and there is still no standard solution to this issue. A
      class of recently investigated metal artifact reduction (MAR) methods based on
      forward projection of a prior image that is artifact-free to replace the metal
      affected projection data have shown promising results. However, usually it is
      hard to get a good prior image which is close to the true image without
      artifacts. This work aims at creating a good prior image so that the forward
      projection can replace the metal affected projection data well. METHODS: The
      proposed method consists of four steps based on the forward projection MAR
      framework. First, metal implants in the reconstructed image are segmented and the
      corresponding metal traces in the projection domain are identified. Then the
      prior image is obtained by two steps. A processed precorrected image is generated
      as an initial prior image first and then in the next step it is used as the
      initial image of the iterative reconstruction from the unaffected projection data
      to generate a better prior image. In order to deal with severe artifacts, the
      iteration incorporates the total variation minimization constraint as well as a
      novel constraint which forces the soft tissue region near metal to be as flat as
      possible. Finally, the projection is completed using forward projection of the
      prior image and the corrected image is reconstructed by FBP. A linear
      interpolation MAR method and two recently reported forward projection based
      methods are performed simultaneously for comparison. RESULTS: The proposed method
      shows outstanding performance on both phantoms' and patients' datasets. This
      approach can reduce artifacts dramatically and restore tissue structures near
      metal to a large extent. Unlike competing MAR methods, it can effectively prevent
      introduction of new artifacts and false structures. Moreover, the proposed method
      has the lowest RMSE in regions of both soft tissue and bone tissue among the
      corrected images and is ranked as the best method for evaluation, by
      radiologists. CONCLUSIONS: Both subjective and quantitative evaluations of the
      results demonstrate the superior performance of the proposed algorithm, compared
      to that of the competing methods. This method offers a remarkable improvement of
      the image quality.

PMID- 23556905
TI  - Site-specific deformable imaging registration algorithm selection using patient
      based simulated deformations.
AB  - PURPOSE: The accuracy of deformable image registration could have a significant
      dosimetric impact in radiation treatment planning. Various image registration
      algorithms have been developed for clinical application. However, validation of
      these algorithms in the current clinical setting remains subjective, relying on
      visual assessment and lacking a comparison to the ground-truth deformation. In
      this study, the authors propose a framework to quantitatively validate various
      image registration solutions by using patient-based synthetic quality assurance
      (QA) phantoms, which can be applied on a site-by-site basis. METHODS: The
      computer-simulated deformation was first generated with virtual deformation QA
      software and further benchmarked using a physical pelvic phantom that was modeled
      after real patient CT images. After the validity of the virtual deformation was
      confirmed, a set of synthetic deformable images was produced to simulate various
      anatomical movements during radiotherapy based on real patient CT images. Three
      patients with head-and-neck, prostate, and spine cancer were included. The
      transformations included bladder filling, soft tissue deformation, mandible, and
      vertebral body movement, etc., which provided various ground-truth images to
      validate deformable registration. Several clinically available deformable
      registration algorithms were tested on these images with multiple registration
      setups, such as global or regional and single-pass or multipass optimization. The
      generated deformation fields and the ground-truth deformation are compared using
      voxel-by-voxel based analysis as well as regional based analysis. RESULTS:
      Performance of registration algorithms varies with clinical sites. The voxel-by
      voxel analysis showed the intensity-based free-form deformation by MIM generated
      the greatest accuracy for low-contrast small regions that underwent significant
      deformation, such as bladder expansion for prostate. However, for large field
      deformations with strong contrast, this approach may increase errors, which is
      especially evident in the cranial spinal irradiation (CSI) case. Both single-pass
      and multipass B-spline registrations performed well for the head-and-neck patient
      and CSI patients. CONCLUSIONS: QA for deformable image registration is essential
      to verify the cumulated dose for accurate adaptive radiotherapy. In this study,
      the authors develop a workflow that can validate image registration techniques
      for several different clinical sites and for various types of deformations using
      patient-based simulated deformations. This work could provide a reference for
      clinicians and radiation physicists on how to choose appropriate image
      registration algorithms for different situations.

PMID- 23556906
TI  - Automated knowledge-based detection of nonobstructive and obstructive arterial
      lesions from coronary CT angiography.
AB  - PURPOSE: Visual analysis of three-dimensional (3D) coronary computed tomography
      angiography (CCTA) remains challenging due to large number of image slices and
      tortuous character of the vessels. The authors aimed to develop a robust,
      automated algorithm for unsupervised computer detection of coronary artery
      lesions. METHODS: The authors' knowledge-based algorithm consists of centerline
      extraction, vessel classification, vessel linearization, lumen segmentation with
      scan-specific lumen attenuation ranges, and lesion location detection. Presence
      and location of lesions are identified using a multi-pass algorithm which
      considers expected or "normal" vessel tapering and luminal stenosis from the
      segmented vessel. Expected luminal diameter is derived from the scan by automated
      piecewise least squares line fitting over proximal and mid segments (67%) of the
      coronary artery considering the locations of the small branches attached to the
      main coronary arteries. RESULTS: The authors applied this algorithm to 42 CCTA
      patient datasets, acquired with dual-source CT, where 21 datasets had 45 lesions
      with stenosis >= 25%. The reference standard was provided by visual and
      quantitative identification of lesions with any stenosis >= 25% by three expert
      readers using consensus reading. The authors algorithm identified 42 lesions
      (93%) confirmed by the expert readers. There were 46 additional lesions detected;
      23 out of 39 (59%) of these were less-stenosed lesions. When the artery was
      divided into 15 coronary segments according to standard cardiology reporting
      guidelines, per-segment basis, sensitivity was 93% and per-segment specificity
      was 81% using 10-fold cross-validation. CONCLUSIONS: The authors' algorithm shows
      promising results in the detection of both obstructive and nonobstructive CCTA
      lesions.

PMID- 23556907
TI  - The detective quantum efficiency of photon-counting x-ray detectors using
      cascaded-systems analyses.
AB  - PURPOSE: Single-photon counting (SPC) x-ray imaging has the potential to improve
      image quality and enable new advanced energy-dependent methods. The purpose of
      this study is to extend cascaded-systems analyses (CSA) to the description of
      image quality and the detective quantum efficiency (DQE) of SPC systems. METHODS:
      Point-process theory is used to develop a method of propagating the mean signal
      and Wiener noise-power spectrum through a thresholding stage (required to
      identify x-ray interaction events). The new transfer relationships are used to
      describe the zero-frequency DQE of a hypothetical SPC detector including the
      effects of stochastic conversion of incident photons to secondary quanta,
      secondary quantum sinks, additive noise, and threshold level. Theoretical results
      are compared with Monte Carlo calculations assuming the same detector model.
      RESULTS: Under certain conditions, the CSA approach can be applied to SPC systems
      with the additional requirement of propagating the probability density function
      describing the total number of image-forming quanta through each stage of a
      cascaded model. Theoretical results including DQE show excellent agreement with
      Monte Carlo calculations under all conditions considered. CONCLUSIONS:
      Application of the CSA method shows that false counts due to additive electronic
      noise results in both a nonlinear image signal and increased image noise. There
      is a window of allowable threshold values to achieve a high DQE that depends on
      conversion gain, secondary quantum sinks, and additive noise.

PMID- 23556908
TI  - Integrated spatiotemporal analysis for automatic contrast agent inflow detection
      on angiography and fluoroscopy during transcatheter aortic valve implantation.
AB  - PURPOSE: In this paper, the authors propose an integrated spatial and temporal
      analysis for automatic detection of contrast agent inflow at the aortic root on
      fluoroscopic and angiographic sequences during transcatheter aortic valve
      implantation procedures as a means to automatically trigger registration of 3D
      aortic models. METHODS: The proposed contrast agent inflow detection method is
      based on a contrast feature curve, calculated using histogram analysis and a
      likelihood ratio test. Several image preprocessing steps are performed to enhance
      the properties of the contrast feature curve. For sequences with a dominant peak
      on its contrast feature curve, a cascaded classifier is then applied to
      differentiate the contrast-enhanced aorta from contrast-enhanced balloons.
      Finally, a multilayer classifier based on sparse Gabor features is used to
      recognize sequences containing a faint contrast-enhanced aorta. RESULTS: The
      algorithm was evaluated using 105 sequences consisting of more than 12,000
      frames, and achieved a detection accuracy of 99.1% (100% sensitivity and 98.5%
      specificity). The computation time for a typical sequence of 150 frames was ~ 1 s
      on a single-core Dell PC with a 1 GHz Intel Xeon processor and 2 GB of RAM.
      CONCLUSIONS: The authors developed a novel, automatic method for contrast agent
      inflow detection on x-ray sequences. With the achieved efficiency and accuracy,
      the proposed method is potentially feasible for clinical use as it facilitates a
      seamless workflow in utilizing patient-specific 3D models to provide anatomical
      details during transcatheter aortic valve implantation procedures.

PMID- 23556909
TI  - Generation of voxelized breast phantoms from surgical mastectomy specimens.
AB  - PURPOSE: In the research and development of dedicated tomographic breast imaging
      systems, digital breast object models, also known as digital phantoms, are useful
      tools. While various digital breast phantoms do exist, the purpose of this study
      was to develop a realistic high-resolution model suitable for simulating three
      dimensional (3D) breast imaging modalities. The primary goal was to design a
      model capable of producing simulations with realistic breast tissue structure.
      METHODS: The methodology for generating an ensemble of digital breast phantoms
      was based on imaging surgical mastectomy specimens using a benchtop, cone-beam
      computed tomography system. This approach allowed low-noise, high-resolution
      projection views of the mastectomy specimens at each angular position.
      Reconstructions of these projection sets were processed using correction
      techniques and diffusion filtering prior to segmentation into breast tissue types
      in order to generate phantoms. RESULTS: Eight compressed digital phantoms and 20
      uncompressed phantoms from which an additional 96 pseudocompressed digital
      phantoms with voxel dimensions of 0.2 mm(3) were generated. Two distinct tissue
      classification models were used in forming breast phantoms. The binary model
      classified each tissue voxel as either adipose or fibroglandular. A multivalue
      scaled model classified each tissue voxel as percentage of adipose tissue (range
      1%-99%). Power spectral analysis was performed to compare simulated
      reconstructions using the breast phantoms to the original breast specimen
      reconstruction, and fits were observed to be similar. CONCLUSIONS: The digital
      breast phantoms developed herein provide a high-resolution anthropomorphic model
      of the 3D uncompressed and compressed breast that are suitable for use in
      evaluating and optimizing tomographic breast imaging modalities. The authors
      believe that other research groups might find the phantoms useful, and therefore
      they offer to make them available for wider use.

PMID- 23556910
TI  - Cascaded-systems analyses and the detective quantum efficiency of single-Z x-ray
      detectors including photoelectric, coherent and incoherent interactions.
AB  - PURPOSE: Theoretical models of the detective quantum efficiency (DQE) of x-ray
      detectors are an important step in new detector development by providing an
      understanding of performance limitations and benchmarks. Previous cascaded
      systems analysis (CSA) models accounted for photoelectric interactions only. This
      paper describes an extension of the CSA approach to incorporate coherent and
      incoherent interactions, important for low-Z detectors such as silicon and
      selenium. METHODS: A parallel-cascade approach is used to describe the three
      types of x-ray interactions. The description of incoherent scatter required
      developing expressions for signal and noise transfer through an "energy-labeled
      reabsorption" process where the parameters describing reabsorption are random
      functions of the scatter photon energy. The description of coherent scatter
      requires the use of scatter form factors that may not be accurate for some
      crystalline detector materials. The model includes the effects of scatter
      reabsorption and escape, charge collection, secondary quantum sinks, noise
      aliasing, and additive noise. Model results are validated by Monte Carlo
      calculations for Si and Se detectors assuming free-atom atomic form factors.
      RESULTS: The new signal and noise transfer expressions were validated by showing
      agreement with Monte Carlo results. Coherent and incoherent scatter can degrade
      the DQE of Si and sometimes Se detectors depending on detector thickness and
      incident-photon energy. Incoherent scatter can produce a substantial low
      frequency drop in the modulation transfer function and DQE. CONCLUSIONS: A
      generally useful CSA model of the DQE is described that is believed valid for any
      single-Z material up to 10 cycles/mm at both mammographic and radiographic
      energies within the limitations of Fourier-based linear-systems models and the
      use of coherent-scatter form factors. The model describes a substantial low
      frequency drop in the DQE of Si systems due to incoherent scatter above 20-40
      keV.

PMID- 23556911
TI  - Measurement of changes in linear accelerator photon energy through flatness
      variation using an ion chamber array.
AB  - PURPOSE: To compare the use of flatness versus percent depth dose (PDD) for
      determining changes in photon beam energy for a megavoltage linear accelerator.
      METHODS: Energy changes were accomplished by adjusting the bending magnet current
      by up to +/- 15% in 5% increments away from the value used clinically. Two
      metrics for flatness, relative flatness in the central 80% of the field (Flat)
      and average maximum dose along the diagonals normalized by central axis dose
      (FDN), were measured using a commercially available planner ionization chamber
      array. PDD was measured in water at depths of 5 and 10 cm in 3 * 3 cm(2) and 10 *
      10 cm(2) fields using a cylindrical chamber. RESULTS: PDD was more sensitive to
      changes in energy when the beam energy was increased than when it was decreased.
      For the 18-MV beam in particular, PDD was not sensitive to energy reductions
      below the nominal energy. The value of Flat was found to be more sensitive to
      decreases in energy than to increases, with little sensitivity to energy
      increases above the nominal energy for 18-MV beams. FDN was the only metric that
      was found to be sensitive to both increases and reductions of energy for both the
      6- and 18-MV beams. CONCLUSIONS: Flatness based metrics were found to be more
      sensitive to energy changes than PDD, In particular, FDN was found to be the most
      sensitive metric to energy changes for photon beams of 6 and 18 MV. The
      ionization chamber array allows this metric to be conveniently measured as part
      of routine accelerator quality assurance.

PMID- 23556912
TI  - Dose response of selected ion chambers in applied homogeneous transverse and
      longitudinal magnetic fields.
AB  - PURPOSE: The magnetic fields of an integrated MR-Linac system will alter the
      paths of electrons that produce ions in the ionization chambers. The dose
      response of selected ion chambers is evaluated in the presence of varying
      transverse and longitudinal magnetic fields. The investigation is useful in
      calibration of therapeutic x-ray beams associated with MR-Linac systems. METHODS:
      The Monte Carlo code PENELOPE was used to model the irradiation of NE2571, and
      PR06C ionization chambers in the presence of a transverse and longitudinal (with
      respect to the photon beam) magnetic fields of varying magnitude. The long axis
      of each chamber was simulated both parallel and perpendicular to the incident
      photon beam for each magnetic field case. The dose deposited in each chamber for
      each case was compared to the case with zero magnetic field by means of a ratio.
      The PR06C chamber's response was measured in the presence of a transverse
      magnetic field with field strengths ranging from 0.0 to 0.2 T to compare to
      simulated results. RESULTS: The simulations and measured data show that in the
      presence of a transverse magnetic field there is a considerable dose response
      (maximum of 11% near 1.0 T in the ion chambers investigated, which depends on the
      magnitude of magnetic field, and relative orientation of the magnetic field,
      radiation beam, and ion chamber. Measurements made with the PR06C chamber verify
      these results in the region of measurement. In contrast, a longitudinal magnetic
      field produces only a slight increase in dose response (2% at 1.5 T) that rises
      slowly with increasing magnetic field and is seemingly independent of chamber
      orientation. Response trends were similar for the two ion chambers and relative
      orientations considered, but slight variations are present from chamber to
      chamber. CONCLUSIONS: Care must be taken when making ion chamber measurements in
      a transverse magnetic field. Ion chamber responses vary not only with transverse
      field strength, but with chamber orientation and type, and can be considerable.
      Longitudinal magnetic fields influence ion chamber responses relatively little
      (2% at 1.5 T), and only at field strengths in excess of 1.0 T.

PMID- 23556913
TI  - ROC analysis in patient specific quality assurance.
AB  - PURPOSE: This work investigates the use of receiver operating characteristic
      (ROC) methods in patient specific IMRT quality assurance (QA) in order to
      determine unbiased methods to set threshold criteria for gamma-distance to
      agreement measurements. METHODS: A group of 17 prostate plans was delivered as
      planned while a second group of 17 prostate plans was modified with the
      introduction of random multileaf collimator (MLC) position errors that are
      normally distributed with sigma ~ +/- 0.5, +/- 1.0, +/- 2.0, and +/- 3.0 mm (a
      total of 68 modified plans were created). All plans were evaluated using five
      different gamma-criteria. ROC methodology was applied by quantifying the fraction
      of modified plans reported as "fail" and unmodified plans reported as "pass."
      RESULTS: gamma-based criteria were able to attain nearly 100%
      sensitivity/specificity in the detection of large random errors (sigma > 3 mm).
      Sensitivity and specificity decrease rapidly for all gamma-criteria as the size
      of error to be detected decreases below 2 mm. Predictive power is null with all
      criteria used in the detection of small MLC errors (sigma < 0.5 mm). Optimal
      threshold values were established by determining which criteria maximized
      sensitivity and specificity. For 3%/3 mm gamma-criteria, optimal threshold values
      range from 92% to 99%, whereas for 2%/2 mm, the range was from 77% to 94%.
      CONCLUSIONS: The optimal threshold values that were determined represent a
      maximized test sensitivity and specificity and are not subject to any user bias.
      When applied to the datasets that we studied, our results suggest the use of
      patient specific QA as a safety tool that can effectively prevent large errors
      (e.g., sigma > 3 mm) as opposed to a tool to improve the quality of IMRT
      delivery.

PMID- 23556914
TI  - Automated chest wall line detection for whole-breast segmentation in sagittal
      breast MR images.
AB  - PURPOSE: Breast magnetic resonance imaging (MRI) plays an important role in the
      clinical management of breast cancer. Computerized analysis is increasingly used
      to quantify breast MRI features in applications such as computer-aided lesion
      detection and fibroglandular tissue estimation for breast cancer risk assessment.
      Automated segmentation of the whole-breast as an organ from the other parts
      imaged is an important step in aiding lesion localization and fibroglandular
      tissue quantification. For this task, identifying the chest wall line (CWL) is
      most challenging due to image contrast variations, intensity discontinuity, and
      bias field. METHODS: In this work, the authors develop and validate a fully
      automated image processing algorithm for accurate delineation of the CWL in
      sagittal breast MRI. The CWL detection is based on an integrated scheme of edge
      extraction and CWL candidate evaluation. The edge extraction consists of applying
      edge-enhancing filters and an edge linking algorithm. Increased accuracy is
      achieved by the synergistic use of multiple image inputs for edge extraction,
      where multiple CWL candidates are evaluated by the dynamic time warping algorithm
      coupled with the construction of a CWL reference. Their method is quantitatively
      validated by a dataset of 60 3D bilateral sagittal breast MRI scans (in total
      3360 2D MR slices) that span the full American College of Radiology Breast
      Imaging Reporting and Data System (BI-RADS) breast density range. Agreement with
      manual segmentation obtained by an experienced breast imaging radiologist is
      assessed by both volumetric and boundary-based metrics, including four
      quantitative measures. RESULTS: In terms of breast volume agreement with manual
      segmentation, the overlay percentage expressed by the Dice's similarity
      coefficient is 95.0% and the difference percentage is 10.1%. More specifically,
      for the segmentation accuracy of the CWL boundary, the CWL overlay percentage is
      92.7% and averaged deviation distance is 2.3 mm. Their method requires ~ 4.5 min
      for segmenting each 3D breast MRI scan (56 slices) in comparison to ~ 35 min
      required for manual segmentation. Further analysis indicates that the
      segmentation performance of their method is relatively stable across the
      different BI-RADS density categories and breast volume, and also robust with
      respect to a varying range of the major parameters of the algorithm. CONCLUSIONS:
      Their fully automated method achieves high segmentation accuracy in a time
      efficient manner. It could support large scale quantitative breast MRI analysis
      and holds the potential to become integrated into the clinical workflow for
      breast cancer clinical applications in the future.

PMID- 23556915
TI  - MR safety assessment of potential RF heating from cranial fixation plates at 7 T.
AB  - PURPOSE: The increasing number of clinically oriented MRI studies at 7 T
      motivates the safety assessment of implants, since many 7 T research sites
      conservatively exclude all subjects with metallic implants, regardless of type or
      location. The purpose of this study was to investigate potential RF-induced
      heating during a 7 T MRI scan using a self-built transmit/receive RF coil in
      patients with implants used for refixation of the bone flap after craniotomy.
      Going beyond standard ASTM safety tests, a comprehensive test procedure for
      safety assessments at 7 T is presented which takes into account the more complex
      coupling of the electromagnetic field with the human body and the implant as well
      as polarization effects. METHODS: The safety assessment consisted of three main
      investigations using (1) numerical simulations in simplified models, (2) electric
      and magnetic field measurements and validation procedures in homogeneous
      phantoms, and (3) analysis of exposure scenarios in a heterogeneous human body
      model including thermal simulations. Finally, 7 T in vivo images show the degree
      of image artifact around the implants. RESULTS: The simulations showed that the
      field distortions remain localized within the direct vicinity of the implants. A
      parallel E-field polarization was found to be the most relevant component in
      creating local SAR deviations, resulting in a 10% increase in 10-g-averaged SAR
      and 53% in 1-g-averaged SAR. Using a heterogeneous human head model, the implants
      caused field distortions and SAR elevations in the numerical simulations which
      were distinctly lower than the maximum local SAR value caused by the RF coil
      alone. Also, the position of the maximum 10-g-averaged SAR remained unchanged by
      the presence of the implants. Similarly, the maximum absolute local temperature
      remained below 39  degrees C in the thermal simulations. Only minor artifacts
      from the implants were observed in the in vivo images that would not likely
      affect the diagnostic image quality in patients. CONCLUSIONS: The findings
      suggested no evidence for noteworthy RF-related heating in humans after
      craniotomy using the described implants and for the particular RF coil that was
      used in this study. Here, identical transmit power restrictions apply with or
      without the implants. For other RF coils, the maximum permissible input power
      should be reduced by 10% until further simulations may indicate otherwise.

PMID- 23556916
TI  - Analog receive signal processing for magnetic particle imaging.
AB  - PURPOSE: Magnetic particle imaging (MPI) applies oscillating magnetic fields to
      determine the distribution of magnetic nanoparticles in vivo. Using a receive
      coil, the change of the particle magnetization can be detected. However, the
      signal induced by the nanoparticles is superimposed by the direct feedthrough
      interference of the sinusoidal excitation field, which couples into the receive
      coils. As the latter is several magnitudes higher, the extraction of the particle
      signal from the excitation signal is a challenging task. METHODS: One way to
      remove the interfering signal is to suppress the excitation signal by means of a
      band-stop filter. However, this technique removes parts of the desired particle
      signal, which are essential for direct reconstruction of the particle
      concentration. A way to recover the entire particle signal is to cancel out the
      excitation signal by coupling a matching cancellation signal into the receive
      chain. However, the suppression rates that can be achieved by signal cancellation
      are not as high as with the filtering method, which limits the sensitivity of
      this method. In order to unite the advantages of both methods, in this work the
      authors propose to combine the filtering and the cancellation technique. All
      methods were compared by measuring 10 MUl Resovist, in the same field generator
      only switching the signal processing parts. RESULTS: The reconstructed time
      signals of the three methods, show the advantage of the proposed combination of
      filtering and cancellation. The method preserves the fundamental frequency and is
      able to detect the tracer signal at its full bandwidth even for low
      concentrations. CONCLUSIONS: By recovering the full particle signal the SNR can
      be improved and errors in the x-space reconstruction are prevented. The authors
      show that the combined method provides this full particle signal and makes it
      possible to improve image quality.

PMID- 23556918
TI  - Manganese-52 positron emission tomography tracer characterization and initial
      results in phantoms and in vivo.
AB  - PURPOSE: Manganese(II) is employed as a contrast agent with magnetic resonance
      imaging (MRI) for study of neuronal activation in rats and mice. However, at the
      concentrations required for MRI, Mn may induce pharmacological or toxic effects.
      Positron emission tomography (PET) imaging of (52)MnCl2 at tracer doses has the
      potential to allow similar Mn studies as manganese-enhanced MRI while providing
      quantitative results and avoiding toxic effects. In this work, (52)MnCl2 is
      produced and characterized as a PET tracer in phantoms and in rats. METHODS:
      (52)MnCl2 was produced by proton irradiation of natural Cr foil and separated by
      column chromatography. Images were acquired on a Siemens Focus 120 small animal
      PET scanner. Phantom images were acquired to assess uniformity, resolution,
      cascade background correction, and count rate linearity. Images of rats were also
      acquired after systemic and intracerebroventricular (ICV) administration of
      (52)MnCl2 to investigate Mn(II) distribution in vivo. RESULTS: Irradiation yield
      was 74.6 +/- 8.5 kBq/MUA min (52)Mn at end of bombardment with initial specific
      activity of at least 3.5 MBq/nmol. (52)Mn PET images show similar uniformity and
      resolution to (18)F. (18)F based detector efficiency normalization is adequate
      for (52)Mn imaging. Subtraction of a rescaled random events distribution from
      sinogram data is effective for cascade correction of (52)Mn PET data. After
      systemic injection, (52)Mn appears in structures throughout the body of rats,
      including bones, liver, intestines, and the pituitary gland, but does not appear
      detectably throughout the brain. After ICV injection, (52)Mn remains in the brain
      and spinal cord. CONCLUSIONS: (52)Mn is a promising tracer for small animal PET
      imaging, yielding image quality comparable to (18)F. Potential applications
      include studies similar to Mn-enhanced neuronal MRI, and in other organ systems
      including bones, spinal cord, and the digestive tract.

PMID- 23556917
TI  - Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the
      effect of variable performance of individual segmentation methods.
AB  - PURPOSE: Many approaches have been proposed to segment high uptake objects in 18F
      fluoro-deoxy-glucose positron emission tomography images but none provides
      consistent performance across the large variety of imaging situations. This study
      investigates the use of two methods of combining individual segmentation methods
      to reduce the impact of inconsistent performance of the individual methods:
      simple majority voting and probabilistic estimation. METHODS: The National
      Electrical Manufacturers Association image quality phantom containing five glass
      spheres with diameters 13-37 mm and two irregularly shaped volumes (16 and 32 cc)
      formed by deforming high-density polyethylene bottles in a hot water bath were
      filled with 18-fluoro-deoxyglucose and iodine contrast agent. Repeated 5-min
      positron emission tomography (PET) images were acquired at 4:1 and 8:1 object-to
      background contrasts for spherical objects and 4.5:1 and 9:1 for irregular
      objects. Five individual methods were used to segment each object: 40%
      thresholding, adaptive thresholding, k-means clustering, seeded region-growing,
      and a gradient based method. Volumes were combined using a majority vote (MJV) or
      Simultaneous Truth And Performance Level Estimate (STAPLE) method. Accuracy of
      segmentations relative to CT ground truth volumes were assessed using the Dice
      similarity coefficient (DSC) and the symmetric mean absolute surface distances
      (SMASDs). RESULTS: MJV had median DSC values of 0.886 and 0.875; and SMASD of
      0.52 and 0.71 mm for spheres and irregular shapes, respectively. STAPLE provided
      similar results with median DSC of 0.886 and 0.871; and median SMASD of 0.50 and
      0.72 mm for spheres and irregular shapes, respectively. STAPLE had significantly
      higher DSC and lower SMASD values than MJV for spheres (DSC, p < 0.0001; SMASD, p
      = 0.0101) but MJV had significantly higher DSC and lower SMASD values compared to
      STAPLE for irregular shapes (DSC, p < 0.0001; SMASD, p = 0.0027). DSC was not
      significantly different between 128 * 128 and 256 * 256 grid sizes for either
      method (MJV, p = 0.0519; STAPLE, p = 0.5672) but was for SMASD values (MJV, p <
      0.0001; STAPLE, p = 0.0164). The best individual method varied depending on
      object characteristics. However, both MJV and STAPLE provided essentially
      equivalent accuracy to using the best independent method in every situation, with
      mean differences in DSC of 0.01-0.03, and 0.05-0.12 mm for SMASD. CONCLUSIONS:
      Combining segmentations offers a robust approach to object segmentation in PET.
      Both MJV and STAPLE improved accuracy and were robust against the widely varying
      performance of individual segmentation methods. Differences between MJV and
      STAPLE are such that either offers good performance when combining volumes.
      Neither method requires a training dataset but MJV is simpler to interpret, easy
      to implement and fast.

PMID- 23556919
TI  - A prototype MR insertable brain PET using tileable GAPD arrays.
AB  - PURPOSE: The aim of this study was to develop a prototype magnetic resonance (MR)
      compatible positron emission tomography (PET) that can be inserted into a MR
      imager and that allows simultaneous PET and MR imaging of the human brain. This
      paper reports the initial results of the authors' prototype brain PET system
      operating within a 3-T magnetic resonance imaging (MRI) system using newly
      developed Geiger-mode avalanche photodiode (GAPD)-based PET detectors, long
      flexible flat cables, position decoder circuit with high multiplexing ratio, and
      digital signal processing with field programmable gate array-based analog to
      digital converter boards. METHODS: A brain PET with 72 detector modules arranged
      in a ring was constructed and mounted in a 3-T MRI. Each PET module was composed
      of cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled to a
      tileable GAPD. The GAPD output charge signals were transferred to preamplifiers
      using 3 m long flat cables. The LYSO and GAPD were located inside the MR bore and
      all electronics were positioned outside the MR bore. The PET detector performance
      was investigated both outside and inside the MRI, and MR image quality was
      evaluated with and without the PET system. RESULTS: The performance of the PET
      detector when operated inside the MRI during MR image acquisition showed no
      significant change in energy resolution and count rates, except for a slight
      degradation in timing resolution with an increase from 4.2 to 4.6 ns.
      Simultaneous PET/MR images of a hot-rod and Hoffman brain phantom were acquired
      in a 3-T MRI. Rods down to a diameter of 3.5 mm were resolved in the hot-rod PET
      image. The activity distribution patterns between the white and gray matter in
      the Hoffman brain phantom were well imaged. The hot-rod and Hoffman brain
      phantoms on the simultaneously acquired MR images obtained with standard
      sequences were observed without any noticeable artifacts, although MR image
      quality requires some improvement. CONCLUSIONS: These results demonstrate that
      the simultaneous acquisition of PET and MR images is feasible using the MR
      insertable PET developed in this study.

PMID- 23556921
TI  - Dosimetry for nonuniform activity distributions: a method for the calculation of
      3D absorbed-dose distribution without the use of voxel S-values, point kernels,
      or Monte Carlo simulations.
AB  - PURPOSE: Nonuniform activity within the target lesions and the critical organs
      constitutes an important limitation for dosimetric estimates in patients treated
      with tumor-seeking radiopharmaceuticals. The tumor control probability and the
      normal tissue complication probability are affected by the distribution of the
      radionuclide in the treated organ/tissue. In this paper, a straightforward method
      for calculating the absorbed dose at the voxel level is described. This new
      method takes into account a nonuniform activity distribution in the target/organ.
      METHODS: The new method is based on the macroscopic S-values (i.e., the S-values
      calculated for the various organs, as defined in the MIRD approach), on the
      definition of the number of voxels, and on the raw-count 3D array, corrected for
      attenuation, scatter, and collimator resolution, in the lesion/organ considered.
      Starting from these parameters, the only mathematical operation required is to
      multiply the 3D array by a scalar value, thus avoiding all the complex operations
      involving the 3D arrays. RESULTS: A comparison with the MIRD approach, fully
      described in the MIRD Pamphlet No. 17, using S-values at the voxel level, showed
      a good agreement between the two methods for (131)I and for (90)Y. CONCLUSIONS:
      Voxel dosimetry is becoming more and more important when performing therapy with
      tumor-seeking radiopharmaceuticals. The method presented here does not require
      calculating the S-values at the voxel level, and thus bypasses the mathematical
      problems linked to the convolution of 3D arrays and to the voxel size. In the
      paper, the results obtained with this new simplified method as well as the
      possibility of using it for other radionuclides commonly employed in therapy are
      discussed. The possibility of using the correct density value of the
      tissue/organs involved is also discussed.

PMID- 23556920
TI  - Performance of a high-sensitivity dedicated cardiac SPECT scanner for striatal
      uptake quantification in the brain based on analysis of projection data.
AB  - PURPOSE: The authors have previously reported the advantages of high-sensitivity
      single-photon emission computed tomography (SPECT) systems for imaging structures
      located deep inside the brain. DaTscan (Isoflupane I-123) is a dopamine
      transporter (DaT) imaging agent that has shown potential for early detection of
      Parkinson disease (PD), as well as for monitoring progression of the disease.
      Realizing the full potential of DaTscan requires efficient estimation of striatal
      uptake from SPECT images. They have evaluated two SPECT systems, a conventional
      dual-head gamma camera with low-energy high-resolution collimators (conventional)
      and a dedicated high-sensitivity multidetector cardiac imaging system (dedicated)
      for imaging tasks related to PD. METHODS: Cramer-Rao bounds (CRB) on precision of
      estimates of striatal and background activity concentrations were calculated from
      high-count, separate acquisitions of the compartments (right striata, left
      striata, background) of a striatal phantom. CRB on striatal and background
      activity concentration were calculated from essentially noise-free projection
      datasets, synthesized by scaling and summing the compartment projection datasets,
      for a range of total detected counts. They also calculated variances of estimates
      of specific-to-nonspecific binding ratios (BR) and asymmetry indices from these
      values using propagation of error analysis, as well as the precision of measuring
      changes in BR on the order of the average annual decline in early PD. RESULTS:
      Under typical clinical conditions, the conventional camera detected 2 M counts
      while the dedicated camera detected 12 M counts. Assuming a normal BR of 5, the
      standard deviation of BR estimates was 0.042 and 0.021 for the conventional and
      dedicated system, respectively. For an 8% decrease to BR = 4.6, the signal-to
      noise ratio were 6.8 (conventional) and 13.3 (dedicated); for a 5% decrease, they
      were 4.2 (conventional) and 8.3 (dedicated). CONCLUSIONS: This implies that PD
      can be detected earlier with the dedicated system than with the conventional
      system; therefore, earlier identification of PD progression should be possible
      with the high-sensitivity dedicated SPECT camera.

PMID- 23556922
TI  - TOPOS: a new topometric patient positioning and tracking system for radiation
      therapy based on structured white light.
AB  - PURPOSE: A patient positioning system for radiation therapy based on structured
      white light and using off-the-shelf hardware components for flexibility and cost
      effectiveness has been developed in house. Increased accuracy, patient comfort,
      abandonment of any skin marks, accelerated workflow, objective reading/recording,
      better usability and robust sensor design, compared to other positioning
      approaches, were the main goals of this work. Another aim was the application of
      a 6 degrees of freedom tracking system working without dose deposition. METHODS:
      Two optical sensors are the main parts of the TOPOS(r) system (Topometrical
      Positioning, cyberTECHNOLOGIES, Germany). The components: cameras, projectors,
      and computers are commercial off-the-shelf products, allowing for low production
      costs. The black/white cameras of the prototype are capable of taking up to 240
      frames per second (resolution: 640 * 488 pixels). The projector has a resolution
      of 1024 * 768 and a refresh rate of 120 Hz. The patient's body surface is
      measured continuously and registered to a reference surface, providing a
      transformation to superimpose the patient's surface to the reference (planning
      CT) surface as best as possible. The execution of the calculated transformation
      provides the correct patient position before the treatment starts. Due to the
      high-speed acquisition of the surfaces, a surveillance of the patient's
      (respiration) motion during treatment is also accomplished. The accuracy of the
      system was determined using a male mannequin. Two treatment sites were evaluated:
      one simulating a head and neck treatment and the other simulating a thoracic wall
      treatment. The mannequin was moved to predefined positions, and shift vectors
      given by the surface registration were evaluated. Additionally manual positioning
      using a color-coding system was evaluated. RESULTS: Two prototypes have been
      developed, each allowing a continuous high density scan of a 500 * 500 * 400
      mm(3) (L * W * D) large volume with a refresh rate of 10 Hz (extendible to 20 Hz
      for a single sensor system). Surface and position correction display, as well as
      respiratory motion, is shown in real-time (delay < 200 ms) using present
      graphical hardware acceleration. For an intuitive view of the patient's
      misalignment, a fast surface registration algorithm has been developed and tested
      and a real-time color-coding technique is proposed and verified that allows the
      user to easily verify the position of the patient. Using first the surface
      registration and then the color coding the best results were obtained: for the
      head and neck case, the mean difference between the actual zero position and the
      final match was 0.1 +/- 0.4, -0.2 +/- 0.7, and -0.1 +/- 0.3 mm in vertical,
      longitudinal, and lateral direction. For the thoracic case, the mean differences
      were 0.3 +/- 0.5, -0.6 +/- 1.9, 0.0 +/- 0.4 mm. CONCLUSIONS: The presented system
      copes with the increasing demand for more accurate patient positioning due to
      more precise irradiation technologies and minimizes the preparation times for
      correct patient alignment, therefore optimizing the treatment workflow. Moreover,
      TOPOS is a versatile and cost effective image guided radiation therapy device. It
      allows an objective rating of the patient's position before and during the
      irradiation and could also be used for respiratory gating or tracking.

PMID- 23556923
TI  - Estimating the viscoelastic modulus of a thrombus using an ultrasonic shear-wave
      approach.
AB  - PURPOSE: Measurements of the viscoelastic properties of a thrombus can be used to
      assess whether blood clots are likely to become occlusive or to break apart and
      leak into the blood circulation and block smaller vessels. An accurate method for
      estimating both the shear elasticity and viscosity of a blood clot in vivo is
      still lacking, which prompted us to use a novel shear-wave approach to measure
      the viscoelastic modulus of blood clots. METHODS: The shear-wave dispersion
      ultrasound vibrometry was used to measure both the elasticity and viscosity of
      blood clots. The experimental system was verified by measuring the viscoelastic
      modulus of phantoms containing gelatin at different concentrations. Blood-clot
      experiments were carried out using porcine whole blood with hematocrits ranging
      from 3% to 40%. The measured values for both clots and gelatin phantoms were
      compared to those obtained using an embedded-sphere method in order to validate
      the accuracy of the viscoelastic modulus estimations. RESULTS: The shear elastic
      modulus increased from 406.9 +/- 15.8 (mean +/- SD) Pa for 3% gelatin to 1587.2
      +/- 28.9 Pa for 7% gelatin, while the viscosity increased from 0.12 +/- 0.02 Pa s
      to 0.86 +/- 0.05 Pa s, respectively. The shear modulus increased from 196.8 +/-
      58.4 Pa for 40%-hematocrit clots to 641.4 +/- 76.3 Pa for 3%-hematocrit clots,
      while the viscosity increased from 0.29 +/- 0.02 Pa s to 0.42 +/- 0.01 Pa s,
      respectively. CONCLUSIONS: The results from the statistical analysis indicated
      that both the embedded-sphere and shear-wave approaches can provide accurate
      estimations of the shear elasticity for clots and gelatin phantoms. In contrast,
      the shear-wave approach as well as other methods of rheological measurements does
      not provide accurate viscosity estimations for blood clots. However, the measured
      viscosity range of 0.29-0.42 Pa s is reasonable for blood clots.

PMID- 23556924
TI  - Needle segmentation using 3D Hough transform in 3D TRUS guided prostate
      transperineal therapy.
AB  - PURPOSE: Prostate adenocarcinoma is the most common noncutaneous malignancy in
      American men with over 200,000 new cases diagnosed each year. Prostate
      interventional therapy, such as cryotherapy and brachytherapy, is an effective
      treatment for prostate cancer. Its success relies on the correct needle implant
      position. This paper proposes a robust and efficient needle segmentation method,
      which acts as an aid to localize the needle in three-dimensional (3D) transrectal
      ultrasound (TRUS) guided prostate therapy. METHODS: The procedure of locating the
      needle in a 3D TRUS image is a three-step process. First, the original 3D
      ultrasound image containing a needle is cropped; the cropped image is then
      converted to a binary format based on its histogram. Second, a 3D Hough transform
      based needle segmentation method is applied to the 3D binary image in order to
      locate the needle axis. The position of the needle endpoint is finally determined
      by an optimal threshold based analysis of the intensity probability distribution.
      The overall efficiency is improved through implementing a coarse-fine searching
      strategy. The proposed method was validated in tissue-mimicking agar phantoms,
      chicken breast phantoms, and 3D TRUS patient images from prostate brachytherapy
      and cryotherapy procedures by comparison to the manual segmentation. The
      robustness of the proposed approach was tested by means of varying parameters
      such as needle insertion angle, needle insertion length, binarization threshold
      level, and cropping size. RESULTS: The validation results indicate that the
      proposed Hough transform based method is accurate and robust, with an achieved
      endpoint localization accuracy of 0.5 mm for agar phantom images, 0.7 mm for
      chicken breast phantom images, and 1 mm for in vivo patient cryotherapy and
      brachytherapy images. The mean execution time of needle segmentation algorithm
      was 2 s for a 3D TRUS image with size of 264 * 376 * 630 voxels. CONCLUSIONS: The
      proposed needle segmentation algorithm is accurate, robust, and suitable for 3D
      TRUS guided prostate transperineal therapy.

PMID- 23556925
TI  - Distribution of lung tissue hysteresis during free breathing.
AB  - PURPOSE: To characterize and quantify free breathing lung tissue motion
      distributions. METHODS: Forty seven patient data sets were acquired using a 4DCT
      protocol consisting of 25 cine scans at abutting couch positions on a 16-slice
      scanner. The tidal volume of each scan was measured by simultaneously acquiring
      spirometry and an abdominal pneumatic bellows. The concept of a characteristic
      breath was developed to manage otherwise natural breathing pattern variations.
      The characteristic breath was found by first dividing the breathing traces into
      individual breaths, from maximum exhalation to maximum exhalation. A linear
      breathing drift model was assumed and the drift removed for each breath. Breaths
      that exceeded one standard deviation in period or amplitude were removed from
      further analysis. A characteristic breath was defined by normalizing each breath
      to a common amplitude, aligning the peak inhalation times for all of the breaths,
      and determining the average time at each tidal volume, keeping inhalation and
      exhalation separate. Breathing motion trajectories were computed using a
      previously published five-dimensional lung tissue trajectory model which
      expresses the position of internal lung tissue, X, as:
      X(v,f:X0)=X0+alpha(X0)v+beta(X0)f, where X0 is the internal lung tissue position
      at zero tidal volume and zero airflow, the scalar values v and f are the measured
      tidal volume and airflow, respectively, and the vectors alpha and beta are fitted
      free parameters. In order to characterize the motion patterns, the trajectory
      elongations were examined throughout the subject's lungs. Elongation was defined
      here by generating a rectangular bounding box with one side parallel to the alpha
      vector and the box oriented in the plane defined by the alpha and beta motion
      vectors. Hysteresis motion was defined as the ratio of the box dimensions aligned
      orthogonal to and parallel to the alpha vector. The 15th and 85th percentile of
      the elongation were used to characterize tissue trajectory hysteresis. RESULTS:
      The 15th and 85th percentile bounding box elongations were 0.090 +/- 0.005 and
      0.083 +/- 0.013 in the upper left lung and 0.187 +/- 0.037 and 0.203 +/- 0.053,
      in the lower left lung. The 15th and 85th percentiles for the upper right lung
      were 0.092 +/- 0.006 and 0.085 +/- 0.013, and 0.184 +/- 0.038, and 0.196 +/-
      0.043 in the lower right lung. Both percentiles were calculated for tidal volume
      displacements between 5 and 15 mm. In the left lung, the average elongations in
      the upper and lower lung were zeta=0.120 +/- 0.064 and zeta=0.090 +/- 0.055,
      respectively. The average elongations in the upper and lower right lung were
      zeta=0.107 +/- 0.060 and zeta=0.082 +/- 0.048, respectively. The elongation
      varied smoothly throughout the lungs. CONCLUSIONS: The hysteresis motion was
      relatively small compared to the volume-filling motion, contributing between 8%
      and 20% of the overall motion. Statistically significant differences were
      observed in the range of hysteresis contribution for upper and lower lung
      regions. The characteristic breath process provided an excellent method for
      defining an average breath. The characteristic breath had continuous tidal volume
      and airflow characteristics when the breath was continuously repeated,useful for
      generating patterns representative of realistic motion for breathing motion
      studies.

PMID- 23556926
TI  - Segmentation of lung lesions on CT scans using watershed, active contours, and
      Markov random field.
AB  - PURPOSE: Lung lesions vary considerably in size, density, and shape, and can
      attach to surrounding anatomic structures such as chest wall or mediastinum.
      Automatic segmentation of the lesions poses a challenge. This work communicates a
      new three-dimensional algorithm for the segmentation of a wide variety of
      lesions, ranging from tumors found in patients with advanced lung cancer to small
      nodules detected in lung cancer screening programs. METHODS: The authors'
      algorithm uniquely combines the image processing techniques of marker-controlled
      watershed, geometric active contours as well as Markov random field (MRF). The
      user of the algorithm manually selects a region of interest encompassing the
      lesion on a single slice and then the watershed method generates an initial
      surface of the lesion in three dimensions, which is refined by the active
      geometric contours. MRF improves the segmentation of ground glass opacity
      portions of part-solid lesions. The algorithm was tested on an anthropomorphic
      thorax phantom dataset and two publicly accessible clinical lung datasets. These
      clinical studies included a same-day repeat CT (prewalk and postwalk scans were
      performed within 15 min) dataset containing 32 lung lesions with one
      radiologist's delineated contours, and the first release of the Lung Image
      Database Consortium (LIDC) dataset containing 23 lung nodules with 6
      radiologists' delineated contours. The phantom dataset contained 22 phantom
      nodules of known volumes that were inserted in a phantom thorax. RESULTS: For the
      prewalk scans of the same-day repeat CT dataset and the LIDC dataset, the mean
      overlap ratios of lesion volumes generated by the computer algorithm and the
      radiologist(s) were 69% and 65%, respectively. For the two repeat CT scans, the
      intra-class correlation coefficient (ICC) was 0.998, indicating high reliability
      of the algorithm. The mean relative difference was -3% for the phantom dataset.
      CONCLUSIONS: The performance of this new segmentation algorithm in delineating
      tumor contour and measuring tumor size illustrates its potential clinical value
      for assisting in noninvasive diagnosis of pulmonary nodules, therapy response
      assessment, and radiation treatment planning.

PMID- 23556927
TI  - Population of anatomically variable 4D XCAT adult phantoms for imaging research
      and optimization.
AB  - PURPOSE: The authors previously developed the 4D extended cardiac-torso (XCAT)
      phantom for multimodality imaging research. The XCAT consisted of highly detailed
      whole-body models for the standard male and female adult, including the cardiac
      and respiratory motions. In this work, the authors extend the XCAT beyond these
      reference anatomies by developing a series of anatomically variable 4D XCAT adult
      phantoms for imaging research, the first library of 4D computational phantoms.
      METHODS: The initial anatomy of each phantom was based on chest-abdomen-pelvis
      computed tomography data from normal patients obtained from the Duke University
      database. The major organs and structures for each phantom were segmented from
      the corresponding data and defined using nonuniform rational B-spline surfaces.
      To complete the body, the authors manually added on the head, arms, and legs
      using the original XCAT adult male and female anatomies. The structures were
      scaled to best match the age and anatomy of the patient. A multichannel large
      deformation diffeomorphic metric mapping algorithm was then used to calculate the
      transform from the template XCAT phantom (male or female) to the target patient
      model. The transform was applied to the template XCAT to fill in any unsegmented
      structures within the target phantom and to implement the 4D cardiac and
      respiratory models in the new anatomy. Each new phantom was refined by checking
      for anatomical accuracy via inspection of the models. RESULTS: Using these
      methods, the authors created a series of computerized phantoms with thousands of
      anatomical structures and modeling cardiac and respiratory motions. The database
      consists of 58 (35 male and 23 female) anatomically variable phantoms in total.
      Like the original XCAT, these phantoms can be combined with existing simulation
      packages to simulate realistic imaging data. Each new phantom contains
      parameterized models for the anatomy and the cardiac and respiratory motions and
      can, therefore, serve as a jumping point from which to create an unlimited number
      of 3D and 4D variations for imaging research. CONCLUSIONS: A population of
      phantoms that includes a range of anatomical variations representative of the
      public at large is needed to more closely mimic a clinical study or trial. The
      series of anatomically variable phantoms developed in this work provide a
      valuable resource for investigating 3D and 4D imaging devices and the effects of
      anatomy and motion in imaging. Combined with Monte Carlo simulation programs, the
      phantoms also provide a valuable tool to investigate patient-specific dose and
      image quality, and optimization for adults undergoing imaging procedures.

PMID- 23556928
TI  - Out-of-atlas likelihood estimation using multi-atlas segmentation.
AB  - PURPOSE: Multi-atlas segmentation has been shown to be highly robust and accurate
      across an extraordinary range of potential applications. However, it is limited
      to the segmentation of structures that are anatomically consistent across a large
      population of potential target subjects (i.e., multi-atlas segmentation is
      limited to "in-atlas" applications). Herein, the authors propose a technique to
      determine the likelihood that a multi-atlas segmentation estimate is
      representative of the problem at hand, and, therefore, identify anomalous regions
      that are not well represented within the atlases. METHODS: The authors derive a
      technique to estimate the out-of-atlas (OOA) likelihood for every voxel in the
      target image. These estimated likelihoods can be used to determine and localize
      the probability of an abnormality being present on the target image. RESULTS:
      Using a collection of manually labeled whole-brain datasets, the authors
      demonstrate the efficacy of the proposed framework on two distinct applications.
      First, the authors demonstrate the ability to accurately and robustly detect
      malignant gliomas in the human brain-an aggressive class of central nervous
      system neoplasms. Second, the authors demonstrate how this OOA likelihood
      estimation process can be used within a quality control context for diffusion
      tensor imaging datasets to detect large-scale imaging artifacts (e.g., aliasing
      and image shading). CONCLUSIONS: The proposed OOA likelihood estimation framework
      shows great promise for robust and rapid identification of brain abnormalities
      and imaging artifacts using only weak dependencies on anomaly morphometry and
      appearance. The authors envision that this approach would allow for application
      specific algorithms to focus directly on regions of high OOA likelihood, which
      would (1) reduce the need for human intervention, and (2) reduce the propensity
      for false positives. Using the dual perspective, this technique would allow for
      algorithms to focus on regions of normal anatomy to ascertain image quality and
      adapt to image appearance characteristics.

PMID- 23556929
TI  - Generation of a suite of 3D computer-generated breast phantoms from a limited set
      of human subject data.
AB  - PURPOSE: The authors previously reported on a three-dimensional computer
      generated breast phantom, based on empirical human image data, including a
      realistic finite-element based compression model that was capable of simulating
      multimodality imaging data. The computerized breast phantoms are a hybrid of two
      phantom generation techniques, combining empirical breast CT (bCT) data with
      flexible computer graphics techniques. However, to date, these phantoms have been
      based on single human subjects. In this paper, the authors report on a new method
      to generate multiple phantoms, simulating additional subjects from the limited
      set of original dedicated breast CT data. The authors developed an image morphing
      technique to construct new phantoms by gradually transitioning between two human
      subject datasets, with the potential to generate hundreds of additional
      pseudoindependent phantoms from the limited bCT cases. The authors conducted a
      preliminary subjective assessment with a limited number of observers (n = 4) to
      illustrate how realistic the simulated images generated with the
      pseudoindependent phantoms appeared. METHODS: Several mesh-based geometric
      transformations were developed to generate distorted breast datasets from the
      original human subject data. Segmented bCT data from two different human subjects
      were used as the "base" and "target" for morphing. Several combinations of
      transformations were applied to morph between the "base' and "target" datasets
      such as changing the breast shape, rotating the glandular data, and changing the
      distribution of the glandular tissue. Following the morphing, regions of skin and
      fat were assigned to the morphed dataset in order to appropriately assign
      mechanical properties during the compression simulation. The resulting morphed
      breast was compressed using a finite element algorithm and simulated mammograms
      were generated using techniques described previously. Sixty-two simulated
      mammograms, generated from morphing three human subject datasets, were used in a
      preliminary observer evaluation where four board certified breast radiologists
      with varying amounts of experience ranked the level of realism (from 1 = "fake"
      to 10 = "real") of the simulated images. RESULTS: The morphing technique was able
      to successfully generate new and unique morphed datasets from the original human
      subject data. The radiologists evaluated the realism of simulated mammograms
      generated from the morphed and unmorphed human subject datasets and scored the
      realism with an average ranking of 5.87 +/- 1.99, confirming that overall the
      phantom image datasets appeared more "real" than "fake." Moreover, there was not
      a significant difference (p > 0.1) between the realism of the unmorphed datasets
      (6.0 +/- 1.95) compared to the morphed datasets (5.86 +/- 1.99). Three of the
      four observers had overall average rankings of 6.89 +/- 0.89, 6.9 +/- 1.24, 6.76
      +/- 1.22, whereas the fourth observer ranked them noticeably lower at 2.94 +/-
      0.7. CONCLUSIONS: This work presents a technique that can be used to generate a
      suite of realistic computerized breast phantoms from a limited number of human
      subjects. This suite of flexible breast phantoms can be used for multimodality
      imaging research to provide a known truth while concurrently producing realistic
      simulated imaging data.

PMID- 23556930
TI  - Ethics and professionalism in medical physics: a survey of AAPM members.
AB  - PURPOSE: To assess current education, practices, attitudes, and perceptions
      pertaining to ethics and professionalism in medical physics. METHODS: A link to a
      web-based survey was distributed to the American Association of Physicists in
      Medicine (AAPM) e-mail membership list, with a follow-up e-mail sent two weeks
      later. The survey included questions about ethics/professionalism education,
      direct personal knowledge of ethically questionable practices in clinical care,
      research, education (teaching and mentoring), and professionalism, respondents'
      assessment of their ability to address ethical/professional dilemmas, and
      demographics. For analysis, reports of unethical or ethically questionable
      practices or behaviors by approximately 40% or more of respondents were
      classified as "frequent." RESULTS: Partial or complete responses were received
      from 18% (1394/7708) of AAPM members. Overall, 60% (827/1377) of the respondents
      stated that they had not received ethics/professionalism education during their
      medical physics training. Respondents currently in training were more likely to
      state that they received instruction in ethics/professionalism (80%, 127/159)
      versus respondents who were post-training (35%, 401/1159). Respondents' preferred
      method of instruction in ethics/professionalism was structured periodic
      discussions involving both faculty and students/trainees. More than 90%
      (1271/1384) supported continuing education in ethics/professionalism and 75%
      (1043/1386) stated they would attend ethics/professionalism sessions at
      professional/scientific meetings. In the research setting, reports about
      ethically questionable authorship assignment were frequent (approximately 40%)
      whereas incidents of ethically questionable practices about human subjects
      protections were quite infrequent (5%). In the clinical setting, there was
      frequent recollection of incidents regarding lack of training, resources and
      skills, and error/incident reporting. In the educational setting, incidents of
      unethical or ethically questionable practices were only frequently recollected
      with respect to mentorship/guidance. With respect to professional conduct,
      favoritism, hostile work/learning environment, and maltreatment of subordinates
      and colleagues were frequently reported. A significantly larger proportion of
      women reported experiences with hostile work/learning environments, favoritism,
      poor mentorship, unfairness in educational settings, and concerns about student
      privacy and confidentiality. CONCLUSIONS: The survey found broad interest in
      ethics/professionalism topics and revealed that these topics were being
      integrated into the curriculum at many institutions. The incorporation of ethics
      and professionalism instruction into both graduate education and postgraduate
      training of medical physicists, and into their subsequent lifelong continuing
      education is important given the nontrivial number of medical physicists who had
      direct personal knowledge of unethical or ethically questionable incidents in
      clinical practice, research, education, and professionalism.

PMID- 23556931
TI  - Comment on "Implementation and experimental results of a 3D tumor tracking using
      robotic couch" [Med. Phys. 39(11), 6957-6969 (2012)].

PMID- 23556932
TI  - Response to "Comment on 'Implementation and experimental results of a 3D tumor
      tracking using robotic couch'" [Med. Phys. 39(11), 6957-6969 (2012)].

PMID- 23556938
TI  - Chaotic dynamics of a frequency-modulated microwave oscillator with time-delayed
      feedback.
AB  - We present a chaotic frequency-modulated microwave source that is governed by a
      simple, first-order nonlinear delay differential equation. When a sinusoidal
      nonlinearity is incorporated, the dynamical behaviors range from fixed-point to
      periodic to chaotic, depending on the feedback strength. When the sinusoidal
      nonlinearity is replaced by a binary nonlinearity, the system exhibits a complex
      periodic attractor with no fixed-point solution.

PMID- 23556939
TI  - Controlling phase multistability in coupled period-doubling oscillators.
AB  - A simple method of switching between coexisting attractors in two coupled period
      doubling oscillators is proposed. It is based on "pulling" phases of oscillations
      into suitable value by means of two periodic forces which simultaneously
      influence the both sub-systems. The frequency and the phase-shift of the forces
      are key parameters of the control. Their choice determines the resulted regime.
      The method is tested on example of coupled Chua's oscillators and exhibits its
      efficiency both for periodic and for chaotic attractors.

PMID- 23556940
TI  - Influence of chaotic synchronization on mixing in the phase space of interacting
      systems.
AB  - Using the concept of the relative metric entropy, we study the influence of the
      synchronization phenomenon on mixing rate in the phase space of deterministic and
      noisy chaotic systems. We show that transition to both complete and phase
      synchronization of chaos is accompanied by the decrease of the level of mixing
      induced by internal nonlinear mechanisms of interacting systems as well as by
      external noise influence. Therefore, the decrease of the mixing rate in the phase
      space of interacting systems may indicate transition to synchronization. The
      obtained results are important for time series analysis in various types of real
      noisy systems (e.g., biological, social, and financial systems).

PMID- 23556941
TI  - Spectral coarse graining for random walks in bipartite networks.
AB  - Many real-world networks display a natural bipartite structure, yet analyzing and
      visualizing large bipartite networks is one of the open challenges in complex
      network research. A practical approach to this problem would be to reduce the
      complexity of the bipartite system while at the same time preserve its
      functionality. However, we find that existing coarse graining methods for
      monopartite networks usually fail for bipartite networks. In this paper, we use
      spectral analysis to design a coarse graining scheme specific for bipartite
      networks, which keeps their random walk properties unchanged. Numerical analysis
      on both artificial and real-world networks indicates that our coarse graining can
      better preserve most of the relevant spectral properties of the network. We
      validate our coarse graining method by directly comparing the mean first passage
      time of the walker in the original network and the reduced one.

PMID- 23556942
TI  - On the existence and multiplicity of one-dimensional solid particle attractors in
      time-dependent Rayleigh-Benard convection.
AB  - For the first time evidence is provided that one-dimensional objects formed by
      the accumulation of tracer particles can emerge in flows of thermogravitational
      nature (in the region of the space of parameters, in which the so-called OS
      (oscillatory solution) flow of the Busse balloon represents the dominant
      secondary mode of convection). Such structures appear as seemingly rigid
      filaments, rotating without changing their shape. The most interesting
      (heretofore unseen) feature of such a class of physical attractors is their
      variety. Indeed, distinct shapes are found for a fixed value of the Rayleigh
      number depending on parameters accounting for particle inertia and viscous drag.
      The fascinating "sea" of existing potential paths, their multiplicity and
      tortuosity are explained according to the granularity of the loci in the physical
      space where conditions for phase locking between the traveling thermofluid
      dynamic disturbance and the "turnover time" of particles in the basic toroidal
      flow are satisfied. It is shown, in particular, how the observed wealth of
      geometric objects and related topological features can be linked to a general
      overarching attractor representing an intrinsic (particle-independent) property
      of the base velocity field.

PMID- 23556943
TI  - Criticality in conserved dynamical systems: experimental observation vs. exact
      properties.
AB  - Conserved dynamical systems are generally considered to be critical. We study a
      class of critical routing models, equivalent to random maps, which can be solved
      rigorously in the thermodynamic limit. The information flow is conserved for
      these routing models and governed by cyclic attractors. We consider two classes
      of information flow, Markovian routing without memory and vertex routing
      involving a one-step routing memory. Investigating the respective cycle length
      distributions for complete graphs, we find log corrections to power-law scaling
      for the mean cycle length, as a function of the number of vertices, and a sub
      polynomial growth for the overall number of cycles. When observing experimentally
      a real-world dynamical system one normally samples stochastically its phase
      space. The number and the length of the attractors are then weighted by the size
      of their respective basins of attraction. This situation is equivalent, for
      theory studies, to "on the fly" generation of the dynamical transition
      probabilities. For the case of vertex routing models, we find in this case power
      law scaling for the weighted average length of attractors, for both conserved
      routing models. These results show that the critical dynamical systems are
      generically not scale-invariant but may show power-law scaling when sampled
      stochastically. It is hence important to distinguish between intrinsic properties
      of a critical dynamical system and its behavior that one would observe when
      randomly probing its phase space.

PMID- 23556944
TI  - Ray chaos in an architectural acoustic semi-stadium system.
AB  - The semi-stadium system is composed of a semicircular cap and a rectilinear
      platform. In this study, a dynamic model of the side, position, and angle
      variables is applied to investigate the acoustic ray chaos of the architectural
      semi-stadium system. The Lyapunov exponent is calculated in order to
      quantitatively describe ray instability. The model can be reduced to the semi
      circular and rectilinear platform systems when the rectilinear length is
      sufficiently small and large. The quasi-rectilinear platform and the semicircular
      systems both produce regular trajectories with the maximal Lyapunov exponent
      approaching zero. Ray localizations, such as flutter-echo and sound focusing, are
      found in these two systems. However, the semi-stadium system produces chaotic ray
      behaviors with positive Lyapunov exponents and reduces ray localizations.
      Furthermore, as the rectilinear length increases, the scaling laws of the
      Lyapunov exponent of the semi-stadium system are revealed and compared with those
      of the stadium system. The results suggest the potential application of the
      proposed model to simulate chaotic dynamics of acoustic ray in architectural
      enclosed systems.

PMID- 23556945
TI  - Topological field theory of dynamical systems. II.
AB  - This paper is a continuation of the study [Chaos.22.033134] of the relation
      between the stochastic dynamical systems (DS) and the Witten-type topological
      field theories (TFT). Here, it is discussed that the stochastic expectation
      values of a DS must be complemented on the TFT side by (-1)(F^), where F^ is the
      ghost number operator. The role of this inclusion is to unfold the natural path
      integral representation of the TFT, i.e., the Witten index that equals up to a
      topological constant to the partition function of the stochastic noise, into the
      physical partition function of TFT/DS. It is also shown that on the DS side, the
      TFT's wavefunctions are the conditional probability densities.

PMID- 23556946
TI  - The estimation of neurotransmitter release probability in feedforward neuronal
      network based on adaptive synchronization.
AB  - In this paper, we proposed a new approach to estimate unknown parameters and
      topology of a neuronal network based on the adaptive synchronization control
      scheme. A virtual neuronal network is constructed as an observer to track the
      membrane potential of the corresponding neurons in the original network. When
      they achieve synchronization, the unknown parameters and topology of the original
      network are obtained. The method is applied to estimate the real-time status of
      the connection in the feedforward network and the neurotransmitter release
      probability of unreliable synapses is obtained by statistic computation.
      Numerical simulations are also performed to demonstrate the effectiveness of the
      proposed adaptive controller. The obtained results may have important
      implications in system identification in neural science.

PMID- 23556947
TI  - Levy noise induced switch in the gene transcriptional regulatory system.
AB  - The study of random fluctuations in a gene transcriptional regulatory system is
      extended to the case of non-Gaussian Levy noise, which can describe unpredictable
      jump changes of the random environment. The stationary probability densities are
      given to explore the key roles of Levy noise in a gene transcriptional regulatory
      system. The results demonstrate that the parameters of Levy noise, including
      noise intensity, stability index, and skewness parameter, can induce switches
      between distinct gene-expression states. A further concern is the switching time
      (from the high concentration state to the low concentration one or from the low
      concentration state to the high concentration one), which is a random variable
      and often referred to as the mean first passage time. The effects of Levy noise
      on expression and degradation time are studied by computing the mean first
      passage time in two directions and a number of different peculiarities of non
      Gaussian Levy noise compared with Gaussian noise are observed.

PMID- 23556948
TI  - Chaos M-ary modulation and demodulation method based on Hamilton oscillator and
      its application in communication.
AB  - Chaotic communication has aroused general interests in recent years, but its
      communication effect is not ideal with the restriction of chaos synchronization.
      In this paper a new chaos M-ary digital modulation and demodulation method is
      proposed. By using region controllable characteristics of spatiotemporal chaos
      Hamilton map in phase plane and chaos unique characteristic, which is sensitive
      to initial value, zone mapping method is proposed. It establishes the map
      relationship between M-ary digital information and the region of Hamilton map
      phase plane, thus the M-ary information chaos modulation is realized. In
      addition, zone partition demodulation method is proposed based on the structure
      characteristic of Hamilton modulated information, which separates M-ary
      information from phase trajectory of chaotic Hamilton map, and the theory
      analysis of zone partition demodulator's boundary range is given. Finally, the
      communication system based on the two methods is constructed on the personal
      computer. The simulation shows that in high speed transmission communications and
      with no chaos synchronization circumstance, the proposed chaotic M-ary modulation
      and demodulation method has outperformed some conventional M-ary modulation
      methods, such as quadrature phase shift keying and M-ary pulse amplitude
      modulation in bit error rate. Besides, it has performance improvement in
      bandwidth efficiency, transmission efficiency and anti-noise performance, and the
      system complexity is low and chaos signal is easy to generate.

PMID- 23556949
TI  - Nucleation pathways on complex networks.
AB  - Identifying nucleation pathway is important for understanding the kinetics of
      first-order phase transitions in natural systems. In the present work, we study
      nucleation pathway of the Ising model in homogeneous and heterogeneous networks
      using the forward flux sampling method, and find that the nucleation processes
      represent distinct features along pathways for different network topologies. For
      homogeneous networks, there always exists a dominant nucleating cluster to which
      relatively small clusters are attached gradually to form the critical nucleus.
      For heterogeneous ones, many small isolated nucleating clusters emerge at the
      early stage of the nucleation process, until suddenly they form the critical
      nucleus through a sharp merging process. Moreover, we also compare the nucleation
      pathways for different degree-mixing networks. By analyzing the properties of the
      nucleating clusters along the pathway, we show that the main reason behind the
      different routes is the heterogeneous character of the underlying networks.

PMID- 23556950
TI  - Characterizing chaotic dynamics from simulations of large strain behavior of a
      granular material under biaxial compression.
AB  - For a given observed time series, it is still a rather difficult problem to
      provide a useful and compelling description of the underlying dynamics. The
      approach we take here, and the general philosophy adopted elsewhere, is to
      reconstruct the (assumed) attractor from the observed time series. From this
      attractor, we then use a black-box modelling algorithm to estimate the underlying
      evolution operator. We assume that what cannot be modeled by this algorithm is
      best treated as a combination of dynamic and observational noise. As a final
      step, we apply an ensemble of techniques to quantify the dynamics described in
      each model and show that certain types of dynamics provide a better match to the
      original data. Using this approach, we not only build a model but also verify the
      performance of that model. The methodology is applied to simulations of a
      granular assembly under compression. In particular, we choose a single time
      series recording of bulk measurements of the stress ratio in a biaxial
      compression test of a densely packed granular assembly-observed during the large
      strain or so-called critical state regime in the presence of a fully developed
      shear band. We show that the observed behavior may best be modeled by structures
      capable of exhibiting (hyper-) chaotic dynamics.

PMID- 23556951
TI  - Self avoiding paths routing algorithm in scale-free networks.
AB  - In this paper, we present a new routing algorithm called "the self avoiding paths
      routing algorithm." Its application to traffic flow in scale-free networks shows
      a great improvement over the so called "efficient routing" protocol while at the
      same time maintaining a relatively low average packet travel time. It has the
      advantage of minimizing path overlapping throughout the network in a self
      consistent manner with a relatively small number of iterations by maintaining an
      equilibrated path distribution especially among the hubs. This results in a
      significant shifting of the critical packet generation rate over which traffic
      congestion occurs, thus permitting the network to sustain more information
      packets in the free flow state. The performance of the algorithm is discussed
      both on a Barabasi-Albert network and real autonomous system network data.

PMID- 23556952
TI  - Bouncing droplets on a billiard table.
AB  - In a set of experiments, Couder et al. demonstrate that an oscillating fluid bed
      may propagate a bouncing droplet through the guidance of the surface waves. I
      present a dynamical systems model, in the form of an iterative map, for a droplet
      on an oscillating bath. I examine the droplet bifurcation from bouncing to
      walking, and prescribe general requirements for the surface wave to support
      stable walking states. I show that in addition to walking, there is a region of
      large forcing that may support the chaotic motion of the droplet. Using the map,
      I then investigate the droplet trajectories in a square (billiard ball) domain. I
      show that in large domains, the long time trajectories are either non-periodic
      dense curves or approach a quasiperiodic orbit. In contrast, in small domains, at
      low forcing, trajectories tend to approach an array of circular attracting sets.
      As the forcing increases, the attracting sets break down and the droplet travels
      throughout space.

PMID- 23556953
TI  - A unified model for the dynamics of driven ribbon with strain and magnetic order
      parameters.
AB  - We develop a unified model to explain the dynamics of driven one dimensional
      ribbon for materials with strain and magnetic order parameters. We show that the
      model equations in their most general form explain several results on driven
      magnetostrictive metallic glass ribbons such as the period doubling route to
      chaos as a function of a dc magnetic field in the presence of a sinusoidal field,
      the quasiperiodic route to chaos as a function of the sinusoidal field for a
      fixed dc field, and induced and suppressed chaos in the presence of an additional
      low amplitude near resonant sinusoidal field. We also investigate the influence
      of a low amplitude near resonant field on the period doubling route. The model
      equations also exhibit symmetry restoring crisis with an exponent close to unity.
      The model can be adopted to explain certain results on magnetoelastic beam and
      martensitic ribbon under sinusoidal driving conditions. In the latter case, we
      find interesting dynamics of a periodic one orbit switching between two
      equivalent wells as a function of an ac magnetic field that eventually makes a
      direct transition to chaos under resonant driving condition. The model is also
      applicable to magnetomartensites and materials with two order parameters.

PMID- 23556954
TI  - Control of a model of DNA division via parametric resonance.
AB  - We study the internal resonance, energy transfer, activation mechanism, and
      control of a model of DNA division via parametric resonance. While the system is
      robust to noise, this study shows that it is sensitive to specific fine scale
      modes and frequencies that could be targeted by low intensity electro-magnetic
      fields for triggering and controlling the division. The DNA model is a chain of
      pendula in a Morse potential. While the (possibly parametrically excited) system
      has a large number of degrees of freedom and a large number of intrinsic time
      scales, global and slow variables can be identified by (1) first reducing its
      dynamic to two modes exchanging energy between each other and (2) averaging the
      dynamic of the reduced system with respect to the phase of the fastest mode.
      Surprisingly, the global and slow dynamic of the system remains Hamiltonian
      (despite the parametric excitation) and the study of its associated effective
      potential shows how parametric excitation can turn the unstable open state into a
      stable one. Numerical experiments support the accuracy of the time-averaged
      reduced Hamiltonian in capturing the global and slow dynamic of the full system.

PMID- 23556955
TI  - Generalized variable projective synchronization of time delayed systems.
AB  - We study generalized variable projective synchronization between two unified time
      delayed systems with constant and modulated time delays. A novel Krasovskii
      Lyapunov functional is constructed and a generalized sufficient condition for
      synchronization is derived analytically using the Lyapunov stability theory and
      adaptive techniques. The proposed scheme is valid for a system of n-numbers of
      first order delay differential equations. Finally, a new neural oscillator is
      considered as a numerical example to show the effectiveness of the proposed
      scheme.

PMID- 23556956
TI  - On the absence of analytic integrability of the Bianchi Class B cosmological
      models.
AB  - We follow Bogoyavlensky's approach to deal with Bianchi class B cosmological
      models. We characterize the analytic integrability of such systems.

PMID- 23556957
TI  - On the geometric formulation of Hamiltonian dynamics.
AB  - Under a proper assignment of a metric and a connection, the (classical) dynamical
      trajectories can be identified as geodesics of the underlying manifold. We show
      how these geometric structures can be derived; specifically, we construct them
      explicitly for configuration and phase spaces of Hamiltonian systems. We
      demonstrate how the correspondence between geometry and dynamics can be applied
      to study the conserved quantities of a dynamical system. Lastly, we demonstrate
      how the mean-curvature of the energy level-sets in phase-space might be
      correlated with strongly chaotic behavior.

PMID- 23556958
TI  - Reducing the vulnerability of network by inserting modular topologies.
AB  - In this paper, we present a strategy whose purpose is to reduce the vulnerability
      of a network via inserting modular topologies. The modular topologies are
      generated as WS small-world random network, which is relatively highly robust.
      Using betweenness and betweenness centrality as the vulnerability measurement,
      the strategy searches for remote nodes with low betweenness in the network and
      sets these nodes to be connected to the modular topologies. We test our strategy
      on some basis networks and the results show sufficient availability of our
      strategy. And by comparing with other methods of adding topologies into the
      network, we show that our strategy is especially efficient in reducing the
      vulnerability of the critical network components.

PMID- 23556959
TI  - Nonautonomous motion study on accelerated and decelerated solitons for the
      variable-coefficient Lenells-Fokas model.
AB  - In this paper, the nonautonomous Lenells-Fokas (LF) model is studied with the
      bilinear method and symbolic computation. Such analytical solutions of the
      nonautonomous LF model as one-soliton, two-soliton, and earthwormons are derived.
      Nonautonomous characteristics are then symbolically and graphically investigated,
      and it is finally found that the soliton velocity is time-dependent, and there
      exist soliton accelerating and decelerating motions. Further, two necessary
      conditions for the occurrence of earthwormon acceleration and deceleration (and
      their alternation) are pointed out.

PMID- 23556960
TI  - Two-particle circular billiards versus randomly perturbed one-particle circular
      billiards.
AB  - We study a two-particle circular billiard containing two finite-size circular
      particles that collide elastically with the billiard boundary and with each
      other. Such a two-particle circular billiard provides a clean example of an
      "intermittent" system. This billiard system behaves chaotically, but the time
      scale on which chaos manifests can become arbitrarily long as the sizes of the
      confined particles become smaller. The finite-time dynamics of this system
      depends on the relative frequencies of (chaotic) particle-particle collisions
      versus (integrable) particle-boundary collisions, and investigating these
      dynamics is computationally intensive because of the long time scales involved.
      To help improve understanding of such two-particle dynamics, we compare the
      results of diagnostics used to measure chaotic dynamics for a two-particle
      circular billiard with those computed for two types of one-particle circular
      billiards in which a confined particle undergoes random perturbations.
      Importantly, such one-particle approximations are much less computationally
      demanding than the original two-particle system, and we expect them to yield
      reasonable estimates of the extent of chaotic behavior in the two-particle system
      when the sizes of confined particles are small. Our computations of recurrence
      rate coefficients, finite-time Lyapunov exponents, and autocorrelation
      coefficients support this hypothesis and suggest that studying randomly perturbed
      one-particle billiards has the potential to yield insights into the aggregate
      properties of two-particle billiards, which are difficult to investigate directly
      without enormous computation times (especially when the sizes of the confined
      particles are small).

PMID- 23556961
TI  - Multi-stage complex contagions.
AB  - The spread of ideas across a social network can be studied using complex
      contagion models, in which agents are activated by contact with multiple
      activated neighbors. The investigation of complex contagions can provide crucial
      insights into social influence and behavior-adoption cascades on networks. In
      this paper, we introduce a model of a multi-stage complex contagion on networks.
      Agents at different stages-which could, for example, represent differing levels
      of support for a social movement or differing levels of commitment to a certain
      product or idea-exert different amounts of influence on their neighbors. We
      demonstrate that the presence of even one additional stage introduces novel
      dynamical behavior, including interplay between multiple cascades, which cannot
      occur in single-stage contagion models. We find that cascades-and hence
      collective action-can be driven not only by high-stage influencers but also by
      low-stage influencers.

PMID- 23556962
TI  - Harnessing quantum transport by transient chaos.
AB  - Chaos has long been recognized to be generally advantageous from the perspective
      of control. In particular, the infinite number of unstable periodic orbits
      embedded in a chaotic set and the intrinsically sensitive dependence on initial
      conditions imply that a chaotic system can be controlled to a desirable state by
      using small perturbations. Investigation of chaos control, however, was largely
      limited to nonlinear dynamical systems in the classical realm. In this paper, we
      show that chaos may be used to modulate or harness quantum mechanical systems. To
      be concrete, we focus on quantum transport through nanostructures, a problem of
      considerable interest in nanoscience, where a key feature is conductance
      fluctuations. We articulate and demonstrate that chaos, more specifically
      transient chaos, can be effective in modulating the conductance-fluctuation
      patterns. Experimentally, this can be achieved by applying an external gate
      voltage in a device of suitable geometry to generate classically inaccessible
      potential barriers. Adjusting the gate voltage allows the characteristics of the
      dynamical invariant set responsible for transient chaos to be varied in a
      desirable manner which, in turn, can induce continuous changes in the statistical
      characteristics of the quantum conductance-fluctuation pattern. To understand the
      physical mechanism of our scheme, we develop a theory based on analyzing the
      spectrum of the generalized non-Hermitian Hamiltonian that includes the effect of
      leads, or electronic waveguides, as self-energy terms. As the escape rate of the
      underlying non-attracting chaotic set is increased, the imaginary part of the
      complex eigenenergy becomes increasingly large so that pointer states are more
      difficult to form, making smoother the conductance-fluctuation pattern.

PMID- 23556963
TI  - On the integrable elliptic cylindrical Kadomtsev-Petviashvili equation.
AB  - There exist two versions of the Kadomtsev-Petviashvili (KP) equation, related to
      the Cartesian and cylindrical geometries of the waves. In this paper, we derive
      and study a new version, related to the elliptic cylindrical geometry. The
      derivation is given in the context of surface waves, but the derived equation is
      a universal integrable model applicable to generic weakly nonlinear weakly
      dispersive waves. We also show that there exist nontrivial transformations
      between all three versions of the KP equation associated with the physical
      problem formulation, and use them to obtain new classes of approximate solutions
      for water waves.

PMID- 23556964
TI  - Topology identification of uncertain nonlinearly coupled complex networks with
      delays based on anticipatory synchronization.
AB  - This paper presents an adaptive anticipatory synchronization based method for
      simultaneous identification of topology and parameters of uncertain nonlinearly
      coupled complex dynamical networks with time delays. An adaptive controller is
      proposed, based on Lyapunov stability theorem and Barbalat's Lemma, to guarantee
      the stability of the anticipatory synchronization manifold between drive and
      response networks. Meanwhile, not only the identification criteria of network
      topology and system parameters are obtained but also the anticipatory time is
      identified. Numerical simulation results illustrate the effectiveness of the
      proposed method.

PMID- 23556965
TI  - Effects of time delay on the stochastic resonance in small-world neuronal
      networks.
AB  - The effects of time delay on stochastic resonance in small-world neuronal
      networks are investigated. Without delay, an intermediate intensity of additive
      noise is able to optimize the temporal response of the neural system to the
      subthreshold periodic signal imposed on all neurons constituting the network. The
      time delay in the coupling process can either enhance or destroy stochastic
      resonance of neuronal activity in the small-world network. In particular,
      appropriately tuned delays can induce multiple stochastic resonances, which
      appear intermittently at integer multiples of the oscillation period of weak
      external forcing. It is found that the delay-induced multiple stochastic
      resonances are most efficient when the forcing frequency is close to the global
      resonance frequency of each individual neuron. Furthermore, the impact of time
      delay on stochastic resonance is largely independent of the small-world topology,
      except for resonance peaks. Considering that information transmission delays are
      inevitable in intra- and inter-neuronal communication, the presented results
      could have important implications for the weak signal detection and information
      propagation in neural systems.

PMID- 23556966
TI  - Cross-correlation detection and analysis for California's electricity market
      based on analogous multifractal analysis.
AB  - A novel method, which we called the analogous multifractal cross-correlation
      analysis, is proposed in this paper to study the multifractal behavior in the
      power-law cross-correlation between price and load in California electricity
      market. In addition, a statistic rhoAMF-XA, which we call the analogous
      multifractal cross-correlation coefficient, is defined to test whether the cross
      correlation between two given signals is genuine or not. Our analysis finds that
      both the price and load time series in California electricity market express
      multifractal nature. While, as indicated by the rhoAMF-XA statistical test, there
      is a huge difference in the cross-correlation behavior between the years 1999 and
      2000 in California electricity markets.

PMID- 23556967
TI  - Conjugate feedback induced suppression and generation of oscillations in the Chua
      circuit: experiments and simulations.
AB  - We study the suppression (amplitude death) and generation of oscillations
      (rhythmogenesis) in the Chua circuit using a feedback term consisting of
      conjugate variables (conjugate feedback). When the independent Chua circuit
      (without feedback) is placed in the oscillatory domain, this conjugate feedback
      induces amplitude death in the system. On the contrary, introducing the conjugate
      feedback in the system exhibiting fixed point behavior results in the generation
      of rhythms. Furthermore, it is observed that the dynamics of the Chua circuit
      could be tuned efficiently by varying the strength of this feedback term. Both
      experimental and numerical results are presented.

PMID- 23556968
TI  - Temporal dynamics and impact of event interactions in cyber-social populations.
AB  - The advance of information technologies provides powerful measures to digitize
      social interactions and facilitate quantitative investigations. To explore large
      scale indoor interactions of a social population, we analyze 18 715 users' Wi-Fi
      access logs recorded in a Chinese university campus during 3 months, and define
      event interaction (EI) to characterize the concurrent interactions of multiple
      users inferred by their geographic coincidences-co-locating in the same small
      region at the same time. We propose three rules to construct a transmission
      graph, which depicts the topological and temporal features of event interactions.
      The vertex dynamics of transmission graph tells that the active durations of EIs
      fall into the truncated power-law distributions, which is independent on the
      number of involved individuals. The edge dynamics of transmission graph reports
      that the transmission durations present a truncated power-law pattern independent
      on the daily and weekly periodicities. Besides, in the aggregated transmission
      graph, low-degree vertices previously neglected in the aggregated static networks
      may participate in the large-degree EIs, which is verified by three data sets
      covering different sizes of social populations with various rendezvouses. This
      work highlights the temporal significance of event interactions in cyber-social
      populations.

PMID- 23556969
TI  - The dynamics of hybrid metabolic-genetic oscillators.
AB  - The synthetic construction of intracellular circuits is frequently hindered by a
      poor knowledge of appropriate kinetics and precise rate parameters. Here, we use
      generalized modeling (GM) to study the dynamical behavior of topological models
      of a family of hybrid metabolic-genetic circuits known as "metabolators." Under
      mild assumptions on the kinetics, we use GM to analytically prove that all
      explicit kinetic models which are topologically analogous to one such circuit,
      the "core metabolator," cannot undergo Hopf bifurcations. Then, we examine more
      detailed models of the metabolator. Inspired by the experimental observation of a
      Hopf bifurcation in a synthetically constructed circuit related to the core
      metabolator, we apply GM to identify the critical components of the synthetically
      constructed metabolator which must be reintroduced in order to recover the Hopf
      bifurcation. Next, we study the dynamics of a re-wired version of the core
      metabolator, dubbed the "reverse" metabolator, and show that it exhibits a
      substantially richer set of dynamical behaviors, including both local and global
      oscillations. Prompted by the observation of relaxation oscillations in the
      reverse metabolator, we study the role that a separation of genetic and metabolic
      time scales may play in its dynamics, and find that widely separated time scales
      promote stability in the circuit. Our results illustrate a generic pipeline for
      vetting the potential success of a circuit design, simply by studying the
      dynamics of the corresponding generalized model.

PMID- 23556970
TI  - Multifractal analysis of validated wind speed time series.
AB  - Multifractal properties of 30 min wind data series recorded at six locations in
      Cadiz (Southern Spain) have been studied in this work with the aim of obtaining
      detailed information for a range of time scales. Wind speed records have been
      validated, applying various quality control tests as a pre-requisite before their
      use, improving the reliability of the results due to the identification of
      incorrect values which have been discarded in the analysis. The scaling of the
      wind speed moments has been analysed and empirical moments scaling exponent
      functions K(q) have been obtained. Although the same critical moment (qcrit) has
      been obtained for all the places, some differences appear in other multifractal
      parameters like gammamax and the value of K(0). These differences have been
      related to the presence of extreme events and zero data values in the data series
      analysed, respectively.

PMID- 23556971
TI  - Non-specular reflections in a macroscopic system with wave-particle duality:
      spiral waves in bounded media.
AB  - Spiral waves in excitable media possess both wave-like and particle-like
      properties. When resonantly forced (forced at the spiral rotation frequency)
      spiral cores travel along straight trajectories, but may reflect from medium
      boundaries. Here, numerical simulations are used to study reflections from two
      types of boundaries. The first is a no-flux boundary which waves cannot cross,
      while the second is a step change in the medium excitability which waves do
      cross. Both small-core and large-core spirals are investigated. The predominant
      feature in all cases is that the reflected angle varies very little with incident
      angle for large ranges of incident angles. Comparisons are made to the theory of
      Biktashev and Holden. Large-core spirals exhibit other phenomena such as binding
      to boundaries. The dynamics of multiple reflections is briefly considered.

PMID- 23556972
TI  - Hierarchical networks, power laws, and neuronal avalanches.
AB  - We show that in networks with a hierarchical architecture, critical dynamical
      behaviors can emerge even when the underlying dynamical processes are not
      critical. This finding provides explicit insight into current studies of the
      brain's neuronal network showing power-law avalanches in neural recordings, and
      provides a theoretical justification of recent numerical findings. Our analysis
      shows how the hierarchical organization of a network can itself lead to power-law
      distributions of avalanche sizes and durations, scaling laws between anomalous
      exponents, and universal functions-even in the absence of self-organized
      criticality or critical points. This hierarchy-induced phenomenon is independent
      of, though can potentially operate in conjunction with, standard dynamical
      mechanisms for generating power laws.

PMID- 23556973
TI  - Effect of multiple time-delay on vibrational resonance.
AB  - We report our investigation on the effect of multiple time-delay on vibrational
      resonance in a single Duffing oscillator and in a system of n Duffing oscillators
      coupled unidirectionally and driven by both a low- and a high-frequency periodic
      force. For the single oscillator, we obtain analytical expressions for the
      response amplitude Q and the amplitude g of the high-frequency force at which
      resonance occurs. The regions in parameter space of enhanced Q at resonance, as
      compared to the case in absence of time-delay, show a bands-like structure. For
      the two-coupled oscillators, we explain all the features of variation of Q with
      the control parameter g. For the system of n-coupled oscillators with a single
      time-delay coupling, the response amplitudes of the oscillators are shown to be
      independent of the time-delay. In the case of a multi time-delayed coupling,
      undamped signal propagation takes place for coupling strength (delta) above a
      certain critical value (denoted as deltau). Moreover, the response amplitude
      approaches a limiting value QL with the oscillator number i. We obtain analytical
      expressions for both deltau and QL.

PMID- 23556974
TI  - Individuality of breathing patterns in patients under noninvasive mechanical
      ventilation evidenced by chaotic global models.
AB  - Autonomous global models based on radial basis functions were obtained from data
      measured from patients under noninvasive mechanical ventilation. Some of these
      models, which are discussed in the paper, turn out to have chaotic or quasi
      periodic solutions, thus providing a first piece of evidence that the underlying
      dynamics of the data used to estimate the global models are likely to be chaotic
      or, at least, have a chaotic component. It is explicitly shown that one of such
      global models produces attractors characterized by a Horseshoe map, two models
      produce toroidal chaos, and one model produces a quasi-periodic regime. These
      topologically inequivalent attractors evidence the individuality of breathing
      profiles observed in patient under noninvasive ventilation.

PMID- 23556975
TI  - Short desynchronization episodes prevail in synchronous dynamics of human brain
      rhythms.
AB  - Neural synchronization is believed to be critical for many brain functions. It
      frequently exhibits temporal variability, but it is not known if this variability
      has a specific temporal patterning. This study explores these
      synchronization/desynchronization patterns. We employ recently developed
      techniques to analyze the fine temporal structure of phase-locking to study the
      temporal patterning of synchrony of the human brain rhythms. We study neural
      oscillations recorded by electroencephalograms in alpha and beta frequency bands
      in healthy human subjects at rest and during the execution of a task. While the
      phase-locking strength depends on many factors, dynamics of synchrony has a very
      specific temporal pattern: synchronous states are interrupted by frequent, but
      short desynchronization episodes. The probability for a desynchronization episode
      to occur decreased with its duration. The transition matrix between synchronized
      and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has
      multiplicity 1, and therefore if the stationary distribution between these states
      is perturbed, the system converges back to the stationary distribution very fast.
      The qualitative similarity of this patterning across different subjects, brain
      states and electrode locations suggests that this may be a general type of
      dynamics for the brain. Earlier studies indicate that not all oscillatory
      networks have this kind of patterning of synchronization/desynchronization
      dynamics. Thus, the observed prevalence of short (but potentially frequent)
      desynchronization events (length of one cycle of oscillations) may have important
      functional implications for the brain. Numerous short desynchronizations (as
      opposed to infrequent, but long desynchronizations) may allow for a quick and
      efficient formation and break-up of functionally significant neuronal assemblies.

PMID- 23556976
TI  - Network-based stochastic competitive learning approach to disambiguation in
      collaborative networks.
AB  - Many patterns have been uncovered in complex systems through the application of
      concepts and methodologies of complex networks. Unfortunately, the validity and
      accuracy of the unveiled patterns are strongly dependent on the amount of
      unavoidable noise pervading the data, such as the presence of homonymous
      individuals in social networks. In the current paper, we investigate the problem
      of name disambiguation in collaborative networks, a task that plays a fundamental
      role on a myriad of scientific contexts. In special, we use an unsupervised
      technique which relies on a particle competition mechanism in a networked
      environment to detect the clusters. It has been shown that, in this kind of
      environment, the learning process can be improved because the network
      representation of data can capture topological features of the input data set.
      Specifically, in the proposed disambiguating model, a set of particles is
      randomly spawned into the nodes constituting the network. As time progresses, the
      particles employ a movement strategy composed of a probabilistic convex mixture
      of random and preferential walking policies. In the former, the walking rule
      exclusively depends on the topology of the network and is responsible for the
      exploratory behavior of the particles. In the latter, the walking rule depends
      both on the topology and the domination levels that the particles impose on the
      neighboring nodes. This type of behavior compels the particles to perform a
      defensive strategy, because it will force them to revisit nodes that are already
      dominated by them, rather than exploring rival territories. Computer simulations
      conducted on the networks extracted from the arXiv repository of preprint papers
      and also from other databases reveal the effectiveness of the model, which turned
      out to be more accurate than traditional clustering methods.

PMID- 23556977
TI  - Compound synchronization of four memristor chaotic oscillator systems and secure
      communication.
AB  - In this paper, a novel kind of compound synchronization among four chaotic
      systems is investigated, where the drive systems have been conceptually divided
      into two categories: scaling drive systems and base drive systems. Firstly, a
      sufficient condition is obtained to ensure compound synchronization among four
      memristor chaotic oscillator systems based on the adaptive technique. Secondly, a
      secure communication scheme via adaptive compound synchronization of four
      memristor chaotic oscillator systems is presented. The corresponding theoretical
      proofs and numerical simulations are given to demonstrate the validity and
      feasibility of the proposed control technique. The unpredictability of scaling
      drive systems can additionally enhance the security of communication. The
      transmitted signals can be split into several parts loaded in the drive systems
      to improve the reliability of communication.

PMID- 23556978
TI  - Coupling and noise induced spiking-bursting transition in a parabolic bursting
      model.
AB  - The transition from tonic spiking to bursting is an important dynamic process
      that carry physiologically relevant information. In this work, coupling and noise
      induced spiking-bursting transition is investigated in a parabolic bursting model
      with specific discussion on their cooperation effects. Fast/slow analysis shows
      that weak coupling may help to induce the bursting by changing the geometric
      property of the fast subsystem so that the original unstable periodical solution
      are stabilized. It turned out that noise can play the similar stabilization role
      and induce bursting at appropriate moderate intensity. However, their cooperation
      may either strengthen or weaken the overall effect depending on the choice of
      noise level.

PMID- 23556980
TI  - Soliton dynamics in media with space stimulated Raman scattering and synchronic
      spatial variation of dispersion and self-phase modulation.
AB  - Solitons dynamics in the frame of the extended nonlinear Schrodinger equation
      taking into account space stimulated Raman scattering (SSRS), synchronic spatial
      variation of inhomogeneous second-order dispersion (SOD), and self-phase
      modulation (SPM) is considered both analytically and numerically. Compensation of
      soliton Raman self-wave number down shift by synchronically increasing SOD and
      SPM is shown. Analytical soliton solution as a result of the equilibrium of SSRS
      and increasing both SOD and SPM is found. Regime of the dynamical equilibrium of
      SSRS and inhomogeneous media with periodical variation of soliton's parameters is
      found. Analytical and numerical results are in a good agreement.

PMID- 23556979
TI  - Robust detection of dynamic community structure in networks.
AB  - We describe techniques for the robust detection of community structure in some
      classes of time-dependent networks. Specifically, we consider the use of
      statistical null models for facilitating the principled identification of
      structural modules in semi-decomposable systems. Null models play an important
      role both in the optimization of quality functions such as modularity and in the
      subsequent assessment of the statistical validity of identified community
      structure. We examine the sensitivity of such methods to model parameters and
      show how comparisons to null models can help identify system scales. By
      considering a large number of optimizations, we quantify the variance of network
      diagnostics over optimizations ("optimization variance") and over randomizations
      of network structure ("randomization variance"). Because the modularity quality
      function typically has a large number of nearly degenerate local optima for
      networks constructed using real data, we develop a method to construct
      representative partitions that uses a null model to correct for statistical noise
      in sets of partitions. To illustrate our results, we employ ensembles of time
      dependent networks extracted from both nonlinear oscillators and empirical
      neuroscience data.

PMID- 23556981
TI  - Tendency to occupy a statistically dominant spatial state of the flow as a
      driving force for turbulent transition.
AB  - The transition from laminar to turbulent fluid motion occurring at large Reynolds
      numbers is generally associated with the instability of the laminar flow. On the
      other hand, since the turbulent flow characteristically appears in the form of
      spatially localized structures (e.g., eddies) filling the flow field, a tendency
      to occupy such a structured state of the flow cannot be ruled out as a driving
      force for turbulent transition. To examine this possibility, we propose a simple
      analytical model that treats the flow as a collection of localized spatial
      structures, each of which consists of elementary cells in which the behavior of
      the particles (atoms or molecules) is uncorrelated. This allows us to introduce
      the Reynolds number, associating it with the ratio between the total phase volume
      for the system and that for the elementary cell. Using the principle of maximum
      entropy to calculate the most probable size distribution of the localized
      structures, we show that as the Reynolds number increases, the elementary cells
      group into the localized structures, which successfully explains turbulent
      transition and some other general properties of turbulent flows. An important
      feature of the present model is that a bridge between the spatial-statistical
      description of the flow and hydrodynamic equations is established. We show that
      the basic assumptions underlying the model, i.e., that the particles are
      indistinguishable and elementary volumes of phase space exist in which the state
      of the particles is uncertain, are involved in the derivation of the Navier
      Stokes equation. Taking into account that the model captures essential features
      of turbulent flows, this suggests that the driving force for the turbulent
      transition is basically the same as in the present model, i.e., the tendency of
      the system to occupy a statistically dominant state plays a key role. The
      instability of the flow at high Reynolds numbers can then be a mechanism to
      initiate structural rearrangement of the flow to find this state.

PMID- 23556982
TI  - Integrated computation of finite-time Lyapunov exponent fields during direct
      numerical simulation of unsteady flows.
AB  - The computation of Lagrangian coherent structures typically involves post
      processing of experimentally or numerically obtained fluid velocity fields to
      obtain the largest finite-time Lyapunov exponent (FTLE) field. However, this
      procedure can be tedious for large-scale complex flows of general interest. In
      this work, an alternative approach involving computation of the FTLE on-the-fly
      during direct numerical simulation of the full three dimensional Navier-Stokes
      equations is developed. The implementation relies on Lagrangian particle tracking
      to compose forward time flow maps, and an Eulerian treatment of the backward time
      flow map [S. Leung, J. Comput. Phys. 230, 3500-3524 (2011)] coupled with a semi
      Lagrangian advection scheme. The flow maps are accurately constructed from a
      sequence of smaller sub-steps stored on disk [S. Brunton and C. Rowley, Chaos 20,
      017503 (2010)], resulting in low CPU and memory requirements to compute evolving
      FTLE fields. Several examples are presented to demonstrate the capability and
      parallel scalability of the approach for a variety of two and three dimensional
      flows.

PMID- 23556983
TI  - Spike phase synchronization in delayed-coupled neural networks: uniform vs. non
      uniform transmission delay.
AB  - In this paper, we investigated phase synchronization in delayed dynamical
      networks. Non-identical spiking Hindmarsh-Rose neurons were considered as
      individual dynamical systems and coupled through a number of network structures
      such as scale-free, Erdos-Renyi, and modular. The individual neurons were coupled
      through excitatory chemical synapses with uniform or distributed time delays. The
      profile of spike phase synchrony was different when the delay was uniform across
      the edges as compared to the case when it was distributed, i.e., different delays
      for the edges. When an identical transmission delay was considered, a quasi
      periodic pattern was observed in the spike phase synchrony. There were specific
      values of delay where the phase synchronization reached to its peaks. The
      behavior of the phase synchronization in the networks with non-uniform delays was
      different with the former case, where the phase synchrony decreased as
      distributed delays introduced to the networks.

PMID- 23556984
TI  - Dust-acoustic Gardner solitons and double layers in dusty plasmas with
      nonthermally distributed ions of two distinct temperatures.
AB  - A rigorous theoretical investigation has been performed on dust-acoustic (DA)
      solitary structures in an unmagnetized dusty plasma, consisting of negatively
      charged mobile dust grains, Boltzmann distributed electrons, and nonthermally
      distributed ions of two distinct temperatures. The Korteweg-de Vries (K-dV),
      modified K-dV (mK-dV) and Gardner equations, and their solitary waves (SWs) and
      double layer (DL) (in case of Gardner equation) solutions are derived by using
      the reductive perturbation technique. The basic features of the DA Gardner
      solitons (GSs) and DLs are studied analytically as well as numerically. It has
      been observed that the GSs significantly differ from K-dV and mK-dV solitons, and
      only positive potential DLs exist in the system. It is also studied that two
      temperature nonthermal ions significantly modify the nature and basic properties
      of the DA SWs. The present investigation can be very effective for understanding
      and studying the nonlinear characteristics of the DA waves in laboratory and
      space dusty plasmas.

PMID- 23556986
TI  - Age-related autoimmunity.
AB  - Older persons have higher autoimmunity but a lower prevalence of autoimmune
      diseases. A possible explanation for this is the expansion of many protective
      regulatory mechanisms highly characteristic in the elderly. Of note is the higher
      production of peripheral T-regulatory cells.The frequent development of
      autoimmunity in the elderly was suggested to take place in part due to the
      selection of T cells with increased affinity to self-antigens or to latent
      viruses. These cells were shown to have a greater ability to be pro-inflammatory,
      thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output
      decreases in association with the loss of thymic capacity to generate new T
      cells. However, to balance the above mentioned autoimmunity and prevent the
      development of autoimmune diseases, there is an age-related increase in
      peripheral CD4+ CD25highFoxP3+ T-regulatory cells. It remains unclear whether
      this is an age-related immune dysfunction or a defense response. Whatever the
      reason, the expansion of T-regulatory cells requires payment in terms of an
      increased incidence of cancer and higher susceptibility to infections.

PMID- 23556985
TI  - The insoluble TGFBIp fraction of the cornea is covalently linked via a disulfide
      bond to type XII collagen.
AB  - TGFBIp, also known as keratoepithelin and betaig-h3, is among the most abundant
      proteins in the human cornea, and approximately 60% is associated with the
      insoluble fraction following extraction in sodium dodecyl sulfate (SDS) sample
      buffer. TGFBIp is of particular interest because a wide range of mutations causes
      amyloid or fuchsinophilic crystalloid deposits in the cornea leading to visual
      impairment. We show that the SDS-insoluble fraction of TGFBIp from porcine and
      human corneas is covalently linked via a reducible bond to the NC3 domain of type
      XII collagen in a TGFBIp:type XII collagen stoichiometric ratio of 2:1. Because
      type XII collagen is anchored to striated collagen fibers of the extracellular
      matrix, its interaction with TGFBIp is likely to provide anchoring for cells to
      the extracellular matrix through the integrin binding capability of TGFBIp.
      Furthermore, the TGFBIp-type XII collagen molecule will affect our understanding
      of the molecular pathogenesis of the TGFBI-linked corneal dystrophies.

PMID- 23556987
TI  - Facial purpura as a complication of upper gastrointestinal endoscopy.

PMID- 23556988
TI  - Pediatric palliative care in Canada and the United States: a qualitative
      metasummary of the needs of patients and families.
AB  - OBJECTIVE: Qualitative research is becoming more common in pediatric palliative
      care and end-of-life care. The present article systematically reviews and
      summarizes qualitative and survey-based research on pediatric palliative and end
      of-life care pertaining to the needs of patients and their families. METHOD:
      Twenty-one qualitative and survey-based studies published between 2000 and 2010
      that met the selection criteria were retrieved from MEDLINE, PsycINFO, and
      CINAHL. All studies reported on the needs of patients and families receiving
      pediatric palliative and end-of-life care--from either the patient's, parent's,
      sibling's, or health care provider's perspective. Findings from these studies
      were aggregated using a metasummary technique. RESULTS: Findings were extracted
      and grouped into the following 10 thematic domains pertaining to patient and
      family needs: interactions with staff, health care delivery and accessibility,
      information needs, bereavement needs, psychosocial needs, spiritual needs, pain
      and symptom management, cultural needs, sibling's needs, and decision making.
      CONCLUSIONS: The results of this metasummary highlight the needs of patients and
      families to be taken into consideration in the creation of high-quality pediatric
      palliative and end-of-life care services and guidelines.

PMID- 23556989
TI  - Longitudinal changes and predictors of caregiving burden while providing end-of
      life care for terminally ill cancer patients.
AB  - BACKGROUND: The effect of caring for a dying cancer patient on caregiving burden
      has been explored primarily in Western-based studies with small samples or in
      studies that did not follow up until the patient's death, but has not yet been
      investigated in Taiwan. OBJECTIVE: The study's goals were (1) to identify the
      trajectory of caregiving burden for family caregivers (FCs) of terminally ill
      cancer patients in Taiwan, and (2) to investigate the determinants of caregiving
      burden in a large sample and with longitudinal follow-ups, until the patient's
      death. METHOD: A prospective, longitudinal study was conducted among 193 FCs. The
      trajectory and determinants of caregiving burden were identified by a generalized
      estimation equation approach. RESULTS: Caregiving burden did not change as the
      patient's death approached. FCs experienced heavy caregiving burden when their
      relative suffered from greater symptom distress or if they were spousal
      caregivers; provided high intensity of assistance to the patient while spending
      fewer hours providing care; reported financial insufficiency; or had lower social
      support, fewer psychological resources, or less confidence in caregiving.
      CONCLUSIONS: Taiwanese family caregivers' carry moderate caregiving burden which
      did not change significantly as the patients' death approached. The effects of
      caregiving burden while providing EOL care to terminally ill cancer patients may
      be tempered substantially by enhancing family caregivers caregiving confidence,
      social support, and psychological resources.

PMID- 23556991
TI  - Amblyopia risk factor prevalence.
AB  - PURPOSE: In 2003, the American Association for Pediatric Ophthalmology and
      Strabismus (AAPOS) published a set of risk factors for amblyopia. The intent was
      to promote uniformity of reporting and development in screening. Because this
      prevalence is not yet known, this meta-analysis is an attempt to estimate it.
      METHODS: Major community preschool eye examination studies were reviewed and
      AAPOS cut-offs estimated. RESULTS: The approximate prevalence of anisometropia is
      1.2%, hyperopia is 6%, astigmatism is 15%, myopia is 0.6%, strabismus is 2.5%,
      and visual acuity less than 20/40 is 6%. The mean combined prevalence is 21% +/-
      2% compared to a prevalence of amblyopia 20/40 and worse of 2.5%. CONCLUSIONS:
      Knowing risk factor prevalence simplifies validation efforts. Amblyopia screening
      with a risk factor sensitivity less than 100% is expected and desirable.

PMID- 23556992
TI  - Sleep can reduce proactive interference.
AB  - Sleep has repeatedly been connected to processes of memory consolidation. While
      extensive research indeed documents beneficial effects of sleep on memory, little
      is yet known about the role of sleep for interference effects in episodic memory.
      Although two prior studies reported sleep to reduce retroactive interference, no
      sleep effect has previously been found for proactive interference. Here we
      applied a study format differing from that employed by the prior studies to
      induce a high degree of proactive interference, and asked participants to encode
      a single list or two interfering lists of paired associates via pure study
      cycles. Testing occurred after 12 hours of diurnal wakefulness or nocturnal
      sleep. Consistent with the prior work, we found sleep in comparison to wake did
      not affect memory for the single list, but reduced retroactive interference. In
      addition we found sleep reduced proactive interference, and reduced retroactive
      and proactive interference to the same extent. The finding is consistent with the
      view that arising benefits of sleep are caused by the reactivation of memory
      contents during sleep, which has been suggested to strengthen and stabilise
      memories. Such stabilisation may make memories less susceptible to competition
      from interfering memories at test and thus reduce interference effects. 

PMID- 23556990
TI  - The use of very-low-dose methadone for palliative pain control and the prevention
      of opioid hyperalgesia.
AB  - BACKGROUND: Opioid dose escalation may cause hyperalgesia, mediated by the N
      methyl-D-aspartate (NMDA) pathway. Methadone is an atypical opioid that inhibits
      hyperalgesia through NMDA-blockade, especially at low doses. OBJECTIVE: To
      evaluate the efficacy of using very-low-dose methadone as the sole long-acting
      opioid agent in a hospice practice. DESIGN: A retrospective, observational study
      of the use of methadone, <=15 mg daily, with as-needed short-acting opiates.
      Adjuvant nonopioid medications included haloperidol, which may have NMDA-blocking
      effects. SETTING/SUBJECTS: We reviewed the records of 240 patients admitted to a
      community-based hospice from July 1, 2011 to April 1, 2012, with data collected
      until hospice discharge or until April 30, 2012. MEASUREMENTS: Descriptive
      statistics were used to summarize patient demographics, medication regimens, and
      reported pain scores measured on a numeric rating scale from 0 to 10. RESULTS:
      All patients received short-acting opiates, in a morphine-equivalent dose of 5 mg
      every 4 hours as needed, while 40% also received methadone at a median daily dose
      of 5 mg. Of those on methadone, almost half received scheduled haloperidol. The
      population had a median reported pain score of 0 and a peak score of 3, with
      similar results seen for cancer and noncancer groups. Two-thirds of patients
      never reported a pain score greater than 3. CONCLUSION: The use of very-low-dose
      methadone in conjunction with adjuvant haloperidol resulted in excellent pain
      control without dose escalation or opioid-induced hyperalgesia, for both cancer
      and noncancer diseases. We conclude that low-dose methadone should be part of
      first-line treatment in palliative pain management.

PMID- 23556993
TI  - Renal myelolipoma: a rare extra-adrenal tumor in a rare site: a case report and
      review of the literature.
AB  - INTRODUCTION: Myelolipomas are uncommon, benign tumors composed of mature adipose
      tissue and hematopoietic elements. They mostly occur in the adrenal glands, but
      extra-adrenal myelolipomas have also been reported in other locations such as the
      presacral region, retroperitoneum, pelvis and mediastinum. Here, we present a
      case of an extra-adrenal myelolipoma in a rare site: the renal parenchyma. To the
      best of our knowledge, it is only the third case reported in this unusual
      location. CASE PRESENTATION: We report a case of primary myelolipoma occurring in
      the kidney of a 55-year-old Moroccan man. We describe the radiological and
      clinicopathologic features of this unusual tumor with a review of the literature,
      and we discuss differential diagnosis of retroperitoneal myelolipomas.
      CONCLUSION: This case is noteworthy because the tumor site was unusual. Although
      renal myelolipoma is rare, it should be considered in the differential diagnosis
      of lesions in this site.

PMID- 23556994
TI  - Predicting suicide attempts among treatment-seeking male alcoholics: an
      exploratory study.
AB  - Documented risk factors for suicide among alcohol-dependent patients are
      sensitive but insufficiently specific to effectively identify individuals who are
      prone to future suicide attempt. As a first step to assess factors not previously
      considered, this pilot study involved a group of male alcohol-dependent patients
      (N = 175) coming to detoxification to examine the potential utility of adverse
      childhood experiences (ACE) along with other documented events to discriminate
      individuals with a history of attempted suicide from their detoxifying peers.
      Family health history questionnaires were used to evaluate their ACEs. Receiver
      operating characteristic (ROC) analysis was applied to examine the predictive
      power of ACEs, alone or in combination with documented risk factors, to lifetime
      history of attempted suicide. Among our participants, 48 (27.4%) had a history of
      a suicide attempt and 156 (89.1%) reported at least one out of the nine
      categories of ACEs. Modeling by ROC analysis, we found that a cutoff of four or
      more ACEs plus a history of personal violence achieved the best predictive power
      to a history of any suicide attempt, producing a sensitivity of 0.7, specificity
      of 0.81, and area under curve of 0.75. A prospective study to replicate and
      extend our findings is necessary. 

PMID- 23556996
TI  - Stewart-Bluefarb syndrome: review of the literature and case report of chronic
      ulcer treatment with heparan sulphate (Cacipliq20(r)).
AB  - Stewart-Bluefarb syndrome (SBS), also known as acroangiodermatitis or pseudo
      Kaposi, is a condition rarely encountered. It involves skin lesions that are
      clinically similar to Kaposi sarcoma but are histologically different, and are
      usually secondary to an underlying arteriovenous fistula. Treatment of this
      disease usually involves the correction of the underlying vascular abnormality,
      with the mainstay of therapy ranging from compression devices for venous stasis,
      limited oral medications (dapsone and erythromycin) and local wound care
      including topical steroids. Different methods of treatment showed varied success
      but none is ideal. We report a case of a lower extremity ulcer in a 22-year-old
      male recently diagnosed with SBS successfully treated with heparan sulphate
      (Cacipliq20(r)).

PMID- 23556995
TI  - Effectiveness of treatment with high-frequency chest wall oscillation in patients
      with bronchiectasis.
AB  - BACKGROUND: High-frequency airway clearance (HFCWC) assist devices generate
      either positive or negative trans-respiratory pressure excursions to produce high
      frequency, small-volume oscillations in the airways.HFCWC can lead to changes in
      volume of 15-57 ml and in flow up to 1.6 L/s, which generate minimal coughing to
      mobilize secretions. The typical treatment lasts 20-30 minutes, and consists of
      short periods of compression at different frequencies, separated by coughing.The
      aim of this study was to find the more efficacious treatment in patients with
      bronchiectasis: traditional techniques of chest physiotherapy (CPT) versus high
      frequency oscillation of the chest wall in patients with bronchiectasis. METHODS:
      37 patients were enrolled. Seven of them were excluded. Computer randomization
      divided the patients into three groups: - 10 patients treated with HFCWO by using
      the Vest(r) Airway Clearance System; - 10 patients treated with traditional
      techniques of air way clearance (PEP bottle, PEP mask, ELTGOL, vibratory positive
      expiratory pressure); - 10 patients received medical therapy only (control
      group). To be eligible for enrollment, participants had to be between 18 and 85
      years old and have a diagnosis of bronchiectasis, confirmed on high resolution
      computed tomography. EXCLUSION CRITERIA: lack of informed consent, signs of
      exacerbation, cystic fibrosis. Before the treatment, each patient had blood
      tests, sputum volume and cell count, pulmonary function tests and on the quality
      of life inventories (MMRC, CAT, BCSS). The results were processed through the
      covariance analysis, performed with the R-Project statistical program. It has
      been considered a positive result p <005. RESULTS: Both treatments (traditional
      CPT and HFCWO) showed a significant improvement in some biochemical and
      functional respiratory tests as well as in the quality of life compared to the
      control group. The use of HFCWO compared to CPT also produced a significant
      improvement in blood inflammation parameter C-RP (p <=0.019), parameters of lung
      functionality associated with bronchial obstruction (FVC, FEV1) (p <=0.006 and p
      <=0.001), and in the dyspnea. Improvement in quality of life scales was noted.
      (BCSS, CAT) (both p <=0.001). No significant changes of total cell counts in
      sputum samples were observed in the two groups. In the HFCWO group a significant
      reduction of neutrophils percentage (p<=0.002) and a significant increase of
      macrophages percentage (p <=0.012). CONCLUSIONS: The HFCWO technique provides an
      improvement both in pulmonary function and quality of life related parameters in
      patients with chronic hypersecretive disease. Since those patients need daily
      airway clearance, this treatment should be included among the principal options
      in chest physiotherapy. The study was registered as ChiCTR-TRC-12002134 at
      http://www.chictr.org.

PMID- 23556998
TI  - Interactions of PAMAM dendrimers with SDS at the solid-liquid interface.
AB  - This work addresses structural and nonequilibrium effects of the interactions
      between well-defined cationic poly(amidoamine) PAMAM dendrimers of generations 4
      and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) at the hydrophilic
      silica-water interface. Neutron reflectometry and quartz crystal microbalance
      with dissipation monitoring were used to reveal the adsorption from premixed
      dendrimer/surfactant solutions as well as sequential addition of the surfactant
      to preadsorbed layers of dendrimers. PAMAM dendrimers of both generations adsorb
      to hydrophilic silica as a compact monolayer, and the adsorption is irreversible
      upon rinsing with salt solution. SDS adsorbs on the dendrimer layer and at low
      bulk concentrations causes the expansion of the dendrimer layers on the surface.
      When the bulk concentration of SDS is increased, the surfactant layer consists of
      aggregates or bilayer-like structures. The adsorption of surfactant is reversible
      upon rinsing, but slight changes of the structure of the preadsorbed PAMAM
      monolayer were observed. The adsorption from premixed solutions close to charge
      neutrality results in thick multilayers, but the surface excess is lower when the
      bulk complexes have a net negative charge. A critical examination of the pathway
      of adsorption for the interactions of SDS with preadsorbed PAMAM monolayers and
      premixed PAMAM/SDS solutions with hydrophilic silica revealed that nonequilibrium
      effects are important only in the latter case, and the application of a
      thermodynamic model to such experimental data would be inappropriate.

PMID- 23556997
TI  - Oral carcinoma with perineural invasion has higher nerve growth factor expression
      and worse prognosis.
AB  - BACKGROUND: This study elucidated the association between histopathological
      factors and the prognosis of oral carcinoma. As the histopathological factors
      were determined from the surgical specimen and this can only be used for the
      choices of postoperative regimens, this study also investigated the linkage
      between prognostic factors and the expression of key molecules to examine the
      feasibility of markers as predictors. METHODS: Clinicopathological factors of 101
      oral carcinomas were cross-analyzed with disease-free survival. The expression of
      nerve growth factor (NGF) and its receptor, tyrosine kinase A receptor, was
      assayed with immunohistochemistry. RESULTS: Nodal metastasis was the most crucial
      clinical predictor for disease-free survival. Perineural invasion (PNI) was an
      independent histopathological predictor for both nodal metastasis (P = 0.004) and
      disease-free survival (P = 0.019). Patients with advanced tumor and PNI exhibited
      the high hazard for tumor progression and poor disease-free survival. NGF
      immunoreactivity in tumors was correlated with PNI (P = 0.005) and neck lymph
      node metastasis (P = 0.036). CONCLUSION: Perineural invasion is the indicator of
      worst prognosis. As NGF immunoreactivity was found to be associated with PNI and
      nodal metastasis, the NGF immunoreactivity of oral carcinoma revealed by
      diagnostic biopsy suggests that alternative therapeutic approaches might be
      appropriate.

PMID- 23556999
TI  - Blood lead levels in children after phase-out of leaded gasoline in Kinshasa, the
      capital of Democratic Republic of Congo (DRC).
AB  - BACKGROUND: The phasing out of lead from gasoline has resulted in a significant
      decrease in blood lead levels (BLLs) in children during the last two decades.
      Tetraethyl lead was phased out in DRC in 2009. The objective of this study was to
      test for reduction in pediatric BLLs in Kinshasa, by comparing BLLs collected in
      2011 (2 years after use of leaded gasoline was phased out) to those collected in
      surveys conducted in 2004 and 2008 by Tuakuila et al. (when leaded gasoline was
      still used). METHODS: We analyzed BLLs in a total of 100 children under 6 years
      of age (Mean +/- SD: 2.9 +/- 1.6 age, 64% boys) using inductively coupled argon
      plasma mass spectrometry (ICP - MS). RESULTS: The prevalence of elevated BLLs (>=
      10 MUg/dL) in children tested was 63% in 2004 [n = 100, GM (95% CI) = 12.4 MUg/dL
      (11.4 - 13.3)] and 71% in 2008 [(n = 55, GM (95% CI) = 11.2 MUg/dL (10.3 -
      14.4)]. In the present study, this prevalence was 41%. The average BLLs for the
      current study population [GM (95% CI) = 8.7 MUg/dL (8.0 - 9.5)] was lower than
      those found by Tuakuila et al. (F = 10.38, p <0.001) as well as the CDC level of
      concern (10 MU/dL), with 3% of children diagnosed with BLLs >= 20 MUg/dL.
      CONCLUSION: These results demonstrate a significant success of the public health
      system in Kinshasa, DRC-achieved by the removal of lead from gasoline. However,
      with increasing evidence that adverse health effects occur at BLLs < 10 MUg/dL
      and no safe BLLs in children has been identified, the BLLs measured in this study
      continue to constitute a major public health concern for Kinshasa. The emphasis
      should shift to examine the contributions of non-gasoline sources to children's
      BLLs: car batteries recycling in certain residences, the traditional use of fired
      clay for the treatment of gastritis by pregnant women and leaded paint.

PMID- 23557000
TI  - The Psoriasis Symptom Diary: development and content validity of a novel patient
      reported outcome instrument.
AB  - BACKGROUND: Chronic plaque psoriasis has a profound impact on a patient's daily
      life. To understand the effects of psoriasis treatments, it is essential to
      assess the patient's experience of symptoms and how they impact their daily life.
      The goal of this study was to develop and establish the content validity of a new
      patient reported outcome (PRO) psoriasis measure. METHODS: The Psoriasis Symptom
      Diary was developed by (i) identifying key plaque psoriasis-related symptoms and
      impacts through qualitative patient interviews (n = 29); (ii) developing an
      initial set of items that captured the key patient experiences; and (iii)
      conducting cognitive interviews to test patient understanding of items selected
      for inclusion in the new psoriasis symptom measure (n = 16). RESULTS: Patients
      noted a variety of symptoms, with plaque-related pain (including related concepts
      of burning and stinging), changes in skin appearance, and itching reported by all
      patients. Patients also expressed notable embarrassment and avoidance of social
      situations, due to the appearance of plaques, and limited mobility. The Psoriasis
      Symptom Diary assesses the severity and impact of symptoms using a 24-hour recall
      period to reduce recall bias and error. CONCLUSIONS: The Psoriasis Symptom Diary
      was developed to assess important symptoms and disease-related impacts in a
      manner consistent with guidelines for establishing the content validity of new
      PRO instruments. Following quantitative psychometric testing, the Psoriasis
      Symptom Diary may support efficacy endpoints in clinical trials.

PMID- 23557001
TI  - Facile one-step synthesis of MPHMes from MesPCl2 (M = Li, Na, K; Mes = 2,4,6
      Me3C6H2).
AB  - Reaction of alkali metals (Li, Na, K) with mesityldichlorophosphane (MesPCl2, Mes
      = 2,4,6-Me3C6H2) in ethereal solvents leads to formation of the corresponding
      mesitylphosphanides MPHMes in good purity and yield. (31)P NMR spectroscopic
      studies in deuterated solvents strongly support a mechanism of the reaction that
      involves protonation/disproportionation steps in which the solvent is the only
      possible proton source. Li(thf)(tmeda)PHMes (1), [Na(tmeda)(MU-PHMes)]infinity
      (2), and [K(pmdeta)(MU-PHMes)]2 (3) (tmeda = N,N,N',N'
      tetramethylethylenediamine, pmdeta = N,N,N',N",N"-pentamethyldiethylenetriamine)
      were obtained; in the solid state, 2 forms zigzag chains while 3 is a dimeric
      compound.

PMID- 23557003
TI  - A new era in sports science: the launch of BMC Sports Science, Medicine and
      Rehabilitation.
AB  - This Editorial celebrates the launch of BMC Sports Science, Medicine and
      Rehabilitation within the BMC series of journals published by BioMed Central. BMC
      Sports Science, Medicine and Rehabilitation incorporates the recently closed
      Sports Medicine, Arthroscopy, Rehabilitation, Therapy & Technology (SMARTT) with
      an expanded scope and Editorial Board. BMC Sports Science, Medicine and
      Rehabilitation will fill its own niche in the BMC series alongside other
      companion journals including BMC Physiology, BMC Musculoskeletal Disorders and
      BMC Surgery.

PMID- 23557002
TI  - Disruption of AP3B1 by a chromosome 5 inversion: a new disease mechanism in
      Hermansky-Pudlak syndrome type 2.
AB  - BACKGROUND: Hermansky-Pudlak syndrome 2 (HPS2; OMIM #608233) is a rare, autosomal
      recessive disorder caused by loss-of-function genetic variations affecting AP3B1,
      which encodes the beta3A subunit of the adaptor-related protein complex 3 (AP3).
      Phenotypic characteristics include reduced pigmentation, absent platelet dense
      granule secretion, neutropenia and reduced cytotoxic T lymphocyte (CTL) and
      natural killer (NK) cell function. To date HPS2 has been associated with non
      synonymous, stop-gain or deletion-insertion nucleotide variations within the
      coding region of AP3B1. CASE PRESENTATION: We describe a consanguineous female
      infant with reduced pigmentation, neutropenia and recurrent infections. Platelets
      displayed reduced aggregation and absent ATP secretion in response to collagen
      and ADP, indicating a platelet dense granule defect. There was increased basal
      surface expression of CD107a (lysosome-associated membrane protein 1(LAMP-1)) on
      NK cells and CTLs from the study subject and a smaller increase in the percentage
      of CD107a positive cells after stimulation compared to most healthy controls.
      Immunoblotting of protein extracts from EBV-transformed lymphoblasts from the
      index case showed absent expression of full-length AP-3 beta3A subunit protein,
      confirming a phenotypic diagnosis of HPS2.The index case displayed a homozygous
      pericentric inv(5)(p15.1q14.1), which was also detected as a heterozygous defect
      in both parents of the index case. No loss of genetic material was demonstrated
      by microarray comparative genome hybridisation at 60kb resolution. Fluorescence
      in-situ hybridisation using the 189.6kb probe RP11-422I12, which maps to 5q14.1,
      demonstrated dual hybridisation to both 5q14.1 and 5p15.1 regions of the inverted
      Chr5. The RP11-422I12 probe maps from intron 1 to intron 16 of AP3B1, thus
      localising the 5q inversion breakpoint to within AP3B1. The probe RP11-211K15,
      which corresponds to an intergenic region on 5p also showed dual hybridisation,
      enabling localisation of the 5p inversion breakpoint. CONCLUSION: This case
      report extends the phenotypic description of the very rare disorder HPS2. Our
      demonstration of a homozygous Chr5 inversion predicted to disrupt AP3B1 gene
      provides a novel pathogenic mechanism for this disorder.

PMID- 23557005
TI  - Transformative and restorative processes: revisiting the question of efficacy of
      indigenous healing.
AB  - Studies of the efficacy of 'traditional' Indigenous healing often fail to
      consider the epistemologies that underlay specific healing traditions, especially
      intrinsic notions of efficacy. In this article, I critically engage the concept
      of efficacy by identifying two somewhat different approaches to the issue of
      outcome. In 'transformative' healing processes, healing is conceptualized as a
      journey in which the outcome goal is a transformed individual. Efficacy, then, is
      about incremental changes toward this goal. In 'restorative' healing processes,
      the goal is termination of the sickness and the restoration of health; efficacy
      is conceptualized as a return to a presickness state. These healing processes are
      illustrated with examples from the Q'eqchi Maya of Belize and Aboriginal peoples
      of Canada.

PMID- 23557004
TI  - Mesohepatectomy with total caudate lobectomy of the liver for hepatocellular
      carcinoma.
AB  - BACKGROUND: Mesohepatectomy with total resection of the caudate lobe and
      extrahepatic bile duct is sometimes performed for hilar cholangiocarcinoma or
      gallbladder carcinoma; however, only a few reports on mesohepatectomy with total
      caudate lobectomy of the liver for hepatocellular carcinoma are available.
      METHODS: A 71-year-old woman was preoperatively diagnosed with hepatocellular
      carcinoma in the central bisections (Couinaud's segments 4, 5, and 8) and the
      paracaval portion of the caudate lobe. Mesohepatectomy with total caudate
      lobectomy of the liver permitted the removal of tumors to provide a cancer-free
      raw surface of the liver. Mobilization of the caudate lobe is an important
      procedure in this surgery. Before the liver parenchyma was dissected, all short
      hepatic veins were ligated and divided from the left to the right side as the
      left lateral section was retracted to the right, and the caudate lobe branches of
      the portal vein and hepatic artery were ligated and divided. After the liver
      parenchymal dissection, both between the left lateral and medial sections and
      between the right anterior and posterior sections, the Glissonean branches of the
      caudate lobe were ligated and divided as the central bisections were anteriorly
      retracted. Finally, liver parenchymal dissection was performed between the
      caudate lobe and the right posterior section, which was along the right side of
      the inferior vena cava. RESULTS: The surgery time was 538 minutes and blood loss
      was 1,207 mL. No blood transfusions were required during or after surgery. The
      postoperative course was uncomplicated. The patient is still alive 25 months
      after hepatectomy. CONCLUSION: Although mesohepatectomy with total caudate
      lobectomy of the liver is technically more difficult than mesohepatectomy of the
      liver because the caudate lobe must be completely detached from the inferior vena
      cava and the hilar plate, it is a safe and effective treatment method in selected
      patients with hepatocellular carcinoma located at both the central bisections and
      the paracaval portion of the caudate lobe.

PMID- 23557006
TI  - Halachic infertility: rabbis, doctors, and the struggle over professional
      boundaries.
AB  - This article analyzes a public controversy surrounding the hormonal treatment of
      infertility associated with observance of rabbinic law to illuminate the reach of
      rabbi-doctor relations in a local configuration of religion and biomedicine that
      I call "kosher medicine." I combine a historical perspective on the evolution of
      religious laws governing menstruation, and the rabbi-doctor relations with a
      contemporary ethnography of these relations and laws to illuminate the interplay
      of continuities, discontinuities, tradition, and modernity and their uses and
      abuses in the contemporary mode of interpenetration between observant Judaism and
      biomedicine. The controversy highlights asymmetric permeations into biomedical
      and rabbinic professional domains. Collaborations persist as long as doctors who
      declare their incompetence in rabbinic law accommodate to demands of rabbis who
      are expert in it and also claim competence to challenge medical decisions. Once a
      doctor demonstrates competence in rabbinic law to challenge rabbinic directives a
      crisis develops.

PMID- 23557007
TI  - The priest's soldiers: HIV therapies, health identities, and forced encampment in
      northern Uganda.
AB  - In this article, I analyze how antiretroviral therapy and associated HIV support
      programs engendered HIV-based health identities in displacement camps in conflict
      affected northern Uganda. Drawing on multisited ethnographic fieldwork I
      conducted between 2006 and 2009, I argue that these health identities were
      intimately tied to the congested physical and social conditions of the
      displacement camp. I argue, too, that the interactions between therapeutic
      practices and biosociality, along with the social observation and labeling of
      people with HIV/AIDS, produced new health identities. Furthermore, the labels
      applied to people with HIV-and adopted by them-reflected a local repertoire of
      meanings associating HIV/AIDS with militarism, Christian missions, camp life, and
      humanitarianism: thus people living with HIV/AIDS were labeled 'the priest's
      soldiers.'

PMID- 23557008
TI  - Grandfathers, Google, and dreams: medical pluralism, globalization, and new
      healing encounters in Ghana.
AB  - Across contemporary Africa, pluralistic medical fields are becoming increasingly
      complex, giving rise to newly emerging constellations of healing practices and a
      vast array of therapeutic possibilities. We present portraits of four
      'traditional' healers in southern Ghana who selectively adapt, adopt, and modify
      elements of biomedical, 'local,' and 'exotic' healing practices in eclectic and
      creative ways, positioning themselves strategically in a highly pluralistic,
      contested, and globalized medical arena. Their practices are informed by
      'traditional' knowledge, passed down through families and acquired through
      spiritually directed dreams, but also from medical textbooks, Google searches,
      'scientific' experimentation, and interactions with the biomedical sector. The
      healers make use of modern information and communication technologies to increase
      their geographical reach, and respond to the opportunities and risks of an
      increasingly global but strongly differentiated therapeutic market. However,
      while apparently transgressing therapeutic boundaries, they are simultaneously
      drawing on a discourse of stabilizing and straddling those boundaries to
      legitimize their practices.

PMID- 23557009
TI  - The ritualization of rehabilitation.
AB  - There is widespread and increasing political interest in devising plans to
      support people who have or have had cancer to recover and recommence 'normal'
      lives. Educating cancer patients for this purpose is a central element in cancer
      rehabilitation in both Europe and the United States. One of the challenges in
      intervention research pertaining to rehabilitation is how to measure and explain
      the effects of a particular rehabilitation program. The social processes of
      particular programs are often a 'closed box' and not taken into consideration
      methodologically or analytically. In this article, we unpack and explicate the
      'closed box' of a particular cancer rehabilitation program in Denmark by drawing
      on approaches from the study of ritual. By analyzing rehabilitation as a ritual
      and as ritualization, we identify and conceptualize some of the transformative
      activities involved in cancer rehabilitation. We highlight the significance of
      the ritual site, its aesthetics, its exaggerations, and the social and temporal
      organization of the program.

PMID- 23557010
TI  - A cautionary tale: the characteristics of two-dimensional distributions and their
      effects on epidemiological studies employing an ecological design.
AB  - In recent years, many spatial epidemiological studies that use proximity of
      subjects to putative sources as a surrogate for exposure have been published and
      are increasingly cited as evidence of environmental problems requiring public
      health interventions. In these studies, the simple finding of a significant,
      positive association between proximity and disease incidence has been interpreted
      as evidence of causality. However, numerous authors have pointed out limitations
      to such interpretations. This, the first of two companion studies, examines the
      effects of analyzing (real and simulated) spatial data using logistic regression.
      Simulation is also employed to explore the statistical power of such analyses to
      detect true effects, quantify the probabilities of Type I and Type II errors, and
      to evaluate a proposed mechanism that explains the observed effects. Results
      indicate that, even when the odds ratios of cases and controls are regressed
      against random or nonsense sources, significant, positive associations are
      observed at frequencies substantially greater than chance. These frequencies
      increase when targets are highly non-uniformly distributed such that, for
      example, false-positive associations are more likely than not when odds ratios
      are regressed against the actual distribution of ultramafic rocks in California.
      The coefficients of true, causal associations are substantially attenuated under
      realistic conditions so that, absent corroborating analyses, there is no non
      arbitrary means of distinguishing causal from spurious or real but non-causal
      associations. Factors affecting where people choose to live act as powerful
      confounders, creating spurious or real but non-causal associations between
      exposure and response variables (as well as between other pairs of variables).
      Consequently, future epidemiological studies that use proximity as a surrogate
      for exposure should be required to include adequate negative control analyses
      and/or other kinds of corroborating analyses before they are accepted for
      publication.

PMID- 23557011
TI  - Causal versus spurious spatial exposure-response associations in health risk
      analysis.
AB  - Many recent health risk assessments have noted that adverse health outcomes are
      significantly statistically associated with proximity to suspected sources of
      health hazard, such as manufacturing plants or point sources of air pollution.
      Using geographic proximity to sources as surrogates for exposure to (possibly
      unknown) releases, spatial ecological studies have identified potential adverse
      health effects based on significant regression coefficients between risk rates
      and distances from sources in multivariate statistical risk models. Although this
      procedure has been fruitful in identifying exposure-response associations, it is
      not always clear whether the resulting regression coefficients have valid causal
      interpretations. Spurious spatial regression and other threats to valid causal
      inference may undermine practical efforts to causally link health effects to
      geographic sources, even when there are clear statistical associations between
      them. This paper demonstrates the methodological problems by examining
      statistical associations and regression coefficients between spatially
      distributed exposure and response variables in a realistic data set for
      California. We find that distance from "nonsense" sources (such as arbitrary
      points or lines) are highly statistically significant predictors of cause
      specific risks, such as traffic fatalities and incidence of Kaposi's sarcoma.
      However, the signs of such associations typically depend on the distance scale
      chosen. This is consistent with theoretical analyses showing that random spatial
      trends (which tend to fluctuate in sign), rather than true causal relations, can
      create statistically significant regression coefficients: spatial location itself
      becomes a confounder for spatially distributed exposure and response variables.
      Hence, extreme caution and careful application of spatial statistical methods are
      warranted before interpreting proximity-based exposure-response relations as
      evidence of a possible or probable causal relation.

PMID- 23557012
TI  - Wild edible plants of Belarus: from Rostafinski's questionnaire of 1883 to the
      present.
AB  - BACKGROUND: Belarus is an Eastern European country, which has been little studied
      ethnobotanically. The aim of the study was to compare largely unpublished 19th
      century sources with more contemporary data on the use of wild food plants.
      METHODS: The information on 19th century uses is based on twelve, mainly
      unpublished, responses to Jozef Rostafinski's questionnaire from 1883, and the
      newly discovered materials of the ethnographer Michal Federowski, who structured
      his data according to Rostafinski's questionnaire and documented it with voucher
      specimens. Rostafinski's questionnaire was concerned mainly with Polish
      territories, but for historical reasons this also encompassed a large part of
      Belarus, and we analyzed only the twelve responses (out of the few hundred
      Rostafinski obtained), which concerned the present Belarus. These data were
      compared with a few 20th century ethnographic sources, and our own 40 interviews
      and questionnaires from Belarus. RESULTS AND DISCUSSION: 58 taxa of wild food
      plants used in the 19th century were identified. Some of them are still used in
      modern Belarus, others are probably completely forgotten. In the 19th century
      several species of wild greens were widely used for making soups. Apart from
      Rumex, other wild greens are now either forgotten or rarely used. The list of
      species used in the 20th and 21st century encompasses 67 taxa. Nearly half of
      them were mentioned by Rostafinski's respondents. The list of fruit species has
      not changed much, although in the 19th century fruits were mainly eaten raw, or
      with dairy or floury dishes, and now apart from being eaten raw, they are
      incorporated in sweet dishes like jams or cakes. Modern comparative data also
      contain several alien species, some of which have escaped from cultivation and
      are gathered from a semi-wild state, as well as children's snacks, which were
      probably collected in the 19th century but were not recorded back then.
      CONCLUSION: The responses to Rostafinski from 1883 present extremely valuable
      historical material as the use of wild food plants in Belarus has since undergone
      drastic changes, similar to those, which have taken place in other Eastern
      European countries.

PMID- 23557014
TI  - Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational
      enzymology.
AB  - Computational enzymology is a rapidly maturing field that is increasingly
      integral to understanding mechanisms of enzyme-catalyzed reactions and their
      practical applications. Combined quantum mechanics/molecular mechanics (QM/MM)
      methods are important in this field. By treating the reacting species with a
      quantum mechanical method (i.e., a method that calculates the electronic
      structure of the active site) and including the enzyme environment with simpler
      molecular mechanical methods, enzyme reactions can be modeled. Here, we review
      QM/MM methods and their application to enzyme-catalyzed reactions to investigate
      fundamental and practical problems in enzymology. A range of QM/MM methods is
      available, from cheaper and more approximate methods, which can be used for
      molecular dynamics simulations, to highly accurate electronic structure methods.
      We discuss how modeling of reactions using such methods can provide detailed
      insight into enzyme mechanisms and illustrate this by reviewing some recent
      applications. We outline some practical considerations for such simulations.
      Further, we highlight applications that show how QM/MM methods can contribute to
      the practical development and application of enzymology, e.g., in the
      interpretation and prediction of the effects of mutagenesis and in drug and
      catalyst design.

PMID- 23557015
TI  - Coexistence of frontal fibrosing alopecia with lichen planus pigmentosus.

PMID- 23557016
TI  - Measurement of G protein-coupled receptor surface expression.
AB  - The quantity of G protein-coupled receptors (GPCRs) expressed on the cell surface
      is an important factor regulating receptor signaling. Maturation,
      internalization, recycling and degradation together determine the net amount of
      receptor surface expression. Understanding every aspect of the receptor lifecycle
      will facilitate the development of therapeutic applications. A number of assays
      for measuring the surface expression of GPCRs are currently available. This
      minireview summarizes the currently available assays and their suitability and
      usage for measuring GPCR surface expression.

PMID- 23557013
TI  - Renal involvement in autoimmune connective tissue diseases.
AB  - Connective tissue diseases (CTDs) are a heterogeneous group of disorders that
      share certain clinical presentations and a disturbed immunoregulation, leading to
      autoantibody production. Subclinical or overt renal manifestations are frequently
      observed and complicate the clinical course of CTDs. Alterations of kidney
      function in Sjogren syndrome, systemic scleroderma (SSc), auto-immune myopathies
      (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE),
      antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA)
      are frequently present and physicians should be aware of that.In SLE, renal
      prognosis significantly improved based on specific classification and treatment
      strategies adjusted to kidney biopsy findings. Patients with scleroderma renal
      crisis (SRC), which is usually characterized by severe hypertension, progressive
      decline of renal function and thrombotic microangiopathy, show a significant
      benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular
      and strict blood pressure control in general. Treatment of the underlying
      autoimmune disorder or discontinuation of specific therapeutic agents improves
      kidney function in most patients with Sjogren syndrome, auto-immune myopathies,
      APSN and RA.In this review we focus on impairment of renal function in relation
      to underlying disease or adverse drug effects and implications on treatment
      decisions.

PMID- 23557017
TI  - Discovery of innovative therapeutics: today's realities and tomorrow's vision. 1.
      Criticisms faced by the pharmaceutical industry.
AB  - The pharmaceutical industry is facing enormous challenges, including reduced
      efficiency, declining innovation, key patent expirations, fierce price
      competition from generics, high regulatory hurdles, and a tarnished image. There
      is a clear need for change in the paradigms designed to address these challenges.
      Pharma has responded by embarking on a range of initiatives. However, along the
      way the industry has accrued critics whose accusations have tainted its
      reputation. The first part of this two-part series will discuss the criticisms
      that have been leveled at the pharmaceutical industry and summarize the
      supporting data for and against these criticisms. The second installment will
      focus on the current challenges facing the pharmaceutical industry and Pharma's
      responses to address these challenges. It will describe the industry's changing
      perspective and new business models for coping with the recent loss of talent and
      declining clinical pipelines as well as present some examples of recent drug
      discovery successes. 

PMID- 23557018
TI  - Occult intraorbital conjunctival inclusion cyst discovered almost 70 years after
      strabismus surgery.
AB  - Orbital conjunctival epithelial inclusion cysts are a rare complication of
      strabismus surgery. A subconjunctival cystic mass with translucent fluid is the
      most common presentation. The authors describe a case of an epithelial inclusion
      cyst presenting as an occult orbital mass during reoperation strabismus surgery
      almost 70 years after strabismus surgery.

PMID- 23557019
TI  - EphB4 cellular kinase activity assayed using an enzymatic protein interaction
      system.
AB  - Receptor tyrosine kinases (RTKs) are important players in various cellular
      processes, including proliferation, migration, metabolism, and neuronal
      development. EphB4 RTK is essential for the development of a functional arterial
      venous network in embryonic and adult neoangiogenesis. To develop novel
      inhibitors of EphB4 that might have applications in severe diseases like cancer
      and retinopathies, assays need to be in place that resemble, in a most
      physiological fashion, the activation and downstream function of the kinase. In
      addition, such assays need to be amenable to high-throughput screening to serve
      efficiently the modern drug discovery processes in the pharmaceutical industry.
      The authors have developed an enzyme fragment complementation assay that measures
      the interaction of a downstream docking protein to the activated and
      phosphorylated full-length EphB4 kinase in cells. The assay is specific, robust,
      and amenable to miniaturization and high-throughput screening. It covers most
      steps in the activation process of EphB4, including ligand binding,
      autophosphorylation, and docking of a downstream interactor. This assay format
      can be transferred to other RTKs and adds an important cell-based kinase assay
      option to researchers in the field.

PMID- 23557020
TI  - Assay development for histone methyltransferases.
AB  - Epigenetic modifications play a crucial role in human diseases. Unlike genetic
      mutations, however, they do not change the underlying DNA sequences. Epigenetic
      phenomena have gained increased attention in the field of cancer research, with
      many studies indicating that they are significantly involved in tumor
      establishment and progression. Histone methyltransferases (HMTs) are a large
      group of enzymes that specifically methylate protein lysine and arginine
      residues, especially in histones, using S-adenosyl-L-methionine (SAM) as the
      methyl donor. However, in general, HMTs have no widely accepted high-throughput
      screening (HTS) assay format, and reference inhibitors are not available for many
      of the enzymes. In this study, we describe the application of a miniaturized,
      radioisotope-based reaction system: the HotSpot(SM) platform for
      methyltransferases. Since this platform employs tritiated SAM as a cofactor, it
      can be applied to the assay of any HMT. The key advantage of this format is that
      any substrate can be used, including peptides, proteins, or even nucleosomes,
      without the need for labeling or any other modifications. Using this platform, we
      have determined substrate specificities, characterized enzyme kinetics, performed
      compound profiling for both lysine and arginine methyltransferases, and carried
      out HTS for a small-library LOPAC against DOT1L. After hit confirmation and
      profiling, we found that suramin inhibited DOT1L, NSD2, and PRMT4 with IC50
      values at a low MUM range.

PMID- 23557021
TI  - Detailed analysis of metagenome datasets obtained from biogas-producing microbial
      communities residing in biogas reactors does not indicate the presence of
      putative pathogenic microorganisms.
AB  - BACKGROUND: In recent years biogas plants in Germany have been supposed to be
      involved in amplification and dissemination of pathogenic bacteria causing severe
      infections in humans and animals. In particular, biogas plants are discussed to
      contribute to the spreading of Escherichia coli infections in humans or chronic
      botulism in cattle caused by Clostridium botulinum. Metagenome datasets of
      microbial communities from an agricultural biogas plant as well as from anaerobic
      lab-scale digesters operating at different temperatures and conditions were
      analyzed for the presence of putative pathogenic bacteria and virulence
      determinants by various bioinformatic approaches. RESULTS: All datasets featured
      a low abundance of reads that were taxonomically assigned to the genus
      Escherichia or further selected genera comprising pathogenic species. Higher
      numbers of reads were taxonomically assigned to the genus Clostridium. However,
      only very few sequences were predicted to originate from pathogenic clostridial
      species. Moreover, mapping of metagenome reads to complete genome sequences of
      selected pathogenic bacteria revealed that not the pathogenic species itself, but
      only species that are more or less related to pathogenic ones are present in the
      fermentation samples analyzed. Likewise, known virulence determinants could
      hardly be detected. Only a marginal number of reads showed similarity to
      sequences described in the Microbial Virulence Database MvirDB such as those
      encoding protein toxins, virulence proteins or antibiotic resistance
      determinants. CONCLUSIONS: Findings of this first study of metagenomic sequence
      reads of biogas producing microbial communities suggest that the risk of
      dissemination of pathogenic bacteria by application of digestates from biogas
      fermentations as fertilizers is low, because obtained results do not indicate the
      presence of putative pathogenic microorganisms in the samples analyzed.

PMID- 23557022
TI  - Beckwith-Wiedemann syndrome: first epigenetic confirmed case report in China.

PMID- 23557023
TI  - Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy
      in asthma patients across Asia: SMARTASIA study.
AB  - BACKGROUND: The use of budesonide/formoterol in a single inhaler for both
      maintenance and reliever therapy is a recommended option for treatment of
      persistent asthma not responding well to inhaled corticosteroid (ICS) alone.
      METHODS: This was a multi-centre open-label study on patients whose asthma
      condition remained inadequately controlled by various asthma treatments other
      than budesonide/formoterol. After a 2-week run-in period, eligible patients
      underwent a 12-week treatment period with budesonide/formoterol (Symbicort
      SMART((r)), 160/4.5 MUg) twice daily plus as needed. Patient's asthma control and
      quality of life were assessed using the 5-item Asthma Control Questionnaire (ACQ
      5) and the standardized Asthma Quality of Life Questionnaire (AQLQ-S),
      respectively. RESULTS: A total of 862 eligible asthma patients who have had
      asthma for a mean duration of 10.73 +/- 12.03 years entered a 12-week treatment
      with budesonide/formoterol maintenance and reliever therapy. During treatment,
      ACQ-5 score improved significantly by 0.58 +/- 0.93 (95% CI, 0.51 to 0.64, P <
      0.0001) from the baseline level of 1.62 +/- 1.00. AQLQ(S) score improved by 0.70
      +/- 0.89 (95% CI, 0.64 to 0.76, P < 0.0001) from baseline. Asthma symptom score
      was also reduced significantly (P < 0.0001); between run-in and treatment
      periods, night- and day-time symptom scores were reduced by 0.32 +/- 0.54 (95%
      CI, 0.28 to 0.35) and 0.30 +/- 0.52 (95% CI, 0.27 to 0.34), respectively. The
      percentage of nights with awakenings due to asthma symptoms was reduced by 11.09
      +/- 26.13% (95% CI, 9.34 to 12.85%), while the percentage of asthma-control and
      symptom-free days increased by 20.90 +/- 34.40% (95% CI, 18.59 to 23.21%) and
      23.89 +/- 34.62% (95% CI, 21.56 to 26.21%), respectively (P < 0.0001). Together
      with the improvement in asthma control, the number of night- and day-time
      inhalations of as-needed reliever medication decreased by 0.30 +/- 0.82 (95% CI,
      0.24 to 0.35) inhalations and 0.30 +/- 0.97 (95% CI, 0.23 to 0.36) inhalations,
      respectively (P < 0.0001). No unexpected adverse events were reported.
      CONCLUSION: During treatment of inadequately controlled asthmatic patients with
      budesonide/formoterol maintenance and reliever therapy, significant improvement
      in patients' asthma control and reductions in asthma symptoms and as-needed
      medication use was observed. Patients' quality of life was improved and the
      treatment was well tolerated. TRIAL REGISTRATION: ClinicalTrial.gov:
      (NCT00939341).

PMID- 23557024
TI  - The catalytic subunit of cAMP-dependent protein kinase A StPKA-c contributes to
      conidiation and early invasion in the phytopathogenic fungus Setosphaeria
      turcica.
AB  - Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is an
      important mediator of signal transduction in eukaryotic cells. Thus, identifying
      its function is necessary to understand the cAMP signaling network. StPKA-c, the
      PKA catalytic subunit gene in Setosphaeria turcica, was investigated by RNA
      interference technology. Transformant strains M3, M5, and M9 with diverse StPKA-c
      silencing efficiency were confirmed by reverse transcription polymerase chain
      reaction and Northern blot. Compared with the wild-type strain 01-23, the
      transformant strains exhibited increased growth rate and significantly decreased
      conidium production. In addition, the ratios of spore germination and
      appressorium formation and penetration were slightly reduced. Relative to the
      wild-type strain, the transformants demonstrated different colony color, greatly
      reduced pathogenicity, and similar HT-toxin activity. Further studies showed that
      the content of intracellular melanin in the transformants significantly
      decreased, and the transcription of transcriptional factor StMR was down
      regulated correspondingly. The transcription and enzyme activity of xylanase was
      also impaired. Thus, we proposed that StPKA-c was mainly involved in the mycelium
      growth, conidiation, and pathogenesis of S. turcica. Furthermore, it was
      positively correlated with the biosyntheses of melanin and xylanase but
      dispensable for the activity of HT-toxin.

PMID- 23557026
TI  - Oral manifestations and their treatment in Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a complex, chronic, systemic, autoimmune disease that
      mainly affects the exocrine glands, especially the salivary and lacrimal glands,
      leading to dryness of the oral and ocular mucosae. Several factors have been
      studied that could explain the glandular hypofunction primarily related to water
      transport. Recent reports have shown alterations in secretory route and
      trafficking in labial salivary glands, explaining alterations in the saliva
      quality. The decrease in salivary flow and qualitative alterations in saliva
      could explain many of the oral manifestations. The exocrine manifestations and
      systemic involvement significantly impact the patient's perception of health
      related quality of life. For this reason and given its systemic nature, the
      treatment of these patients should be multidisciplinary. This review addresses
      some particular oral health aspects of SS patients and focuses on relevant topics
      concerning the treatment and prevention of common oral disorders associated with
      this disease. 

PMID- 23557027
TI  - Gravitational drainage of foam films.
AB  - Gravitational drainage from thick plane vertical soap films and hemispherical
      bubbles is studied experimentally and theoretically. The experiments involve
      microinterferometry kindred to the one used in the experiments in the Scheludko
      cell. The following surfactants were used in the experiments: cationic
      dodecyltrimethylammonium bromide (DTAB), anionic sodium dodecyl sulfate (SDS),
      anionic Pantene shampoo which primarily contains sodium lauryl sulfate, nonionic
      tetraethylene glycol monooctyl ether (C8E4), and nonionic Pluronic (P-123)
      surfactants at different concentrations. The theoretical results explain the
      drainage mechanism and are used to develop a new method of measurement of the
      surface elasticity and to test it on the above-mentioned surfactants.

PMID- 23557025
TI  - Doxycycline speeds up healing of chronic venous ulcers.
AB  - Venous ulcers are common, with an overall prevalence of up to 2% in the general
      population of western countries, and have significant socioeconomic impact.
      Matrix metalloproteinases (MMPs) are involved in the alteration of extracellular
      matrix that could lead to venous ulceration. Sixty-four patients with venous
      ulcers were recruited in a 22-month period. All patients were subjected to the
      most appropriate treatment considering also the patient's wishes (compression
      therapy followed or not by vein surgery). Patients were randomised into two
      groups of 32 persons in each (groups A and B). Patients of group A in addition to
      the basic treatment, described above, received the administration of oral low
      doses of doxycycline 20 mg b.i.d. for 3 months, whereas patients of group B
      received basic treatment only. Healing was assessed by means of direct ulcer
      tracing with computerised planimetry. Group A showed a higher healing rate
      compared with group B. In group B, the lower healing rate was related to higher
      levels of MMP-9; neutrophil gelatinase-associated lipocalin and vascular
      endothelial growth factor, documented in plasma; wound fluid and biopsies
      executed and compared between both groups. Pharmacological treatments, as
      doxycycline administration, which by means of its immunomodulatory and anti
      inflammatory actions, through the inhibition of MMP, could improve extracellular
      matrix functioning and represent a possible solution to support wound healing.

PMID- 23557028
TI  - Skin diseases among schoolchildren in Ghana, Gabon, and Rwanda.
AB  - OBJECTIVES: Skin diseases, especially skin infections, among schoolchildren in
      Africa can be a major health problem. The objective of this study was to
      determine the prevalences of skin diseases among children in rural and urban
      schools in three different African countries and to study the influence of
      socioeconomic level. METHODS: Cross-sectional, population-based studies were
      performed in Ghana, Gabon, and Rwanda. Point prevalences of skin diseases were
      estimated on the basis of physical examination by at least one dermatologist.
      RESULTS: A total of 4839 schoolchildren were seen. The overall prevalence of
      schoolchildren with any skin disease was high and amounted to 34.6% and 42.0% in
      two Ghanaian studies, 45.8% in Gabon, and 26.7% in Rwanda. In children with skin
      diseases, skin infections represented the greatest proportion of disease,
      accounting for 14.7% and 17.6% of skin disease in the Ghanaian studies, and 27.7%
      and 22.7% in Gabon and Rwanda, respectively. Diseases with the highest prevalence
      were tinea capitis and bacterial skin infections, especially in rural areas and
      in schools serving children living at lower socioeconomic levels. CONCLUSIONS:
      The prevalences of skin diseases among African schoolchildren were high. Skin
      infections such as tinea capitis and pyoderma predominated.

PMID- 23557029
TI  - Synthesis and size control of iron(II) hexacyanochromate(III) nanoparticles and
      the effect of particle size on linkage isomerism.
AB  - The controlled synthesis of monodisperse nanoparticles of the cubic Prussian blue
      analogue iron(II) hexacyanochromate(III) is reported along with a kinetic study,
      using cyanide stretching frequencies, showing the variations of the activation
      energy (E(a)) of the linkage isomerism as a function of the particle size. Highly
      reproducible, cubic-shaped iron(II) hexacyanochromate(III) nanocrystals, with
      sizes ranging from 2 to 50 nm, are synthesized using a microemulsion technique,
      whereas a bulk synthesis yields nonuniform less monodisperse particles with sizes
      greater than 100 nm. Monitoring the cyanide stretching frequency with FTIR
      spectroscopy shows that the rate of isomerization is faster for smaller
      particles. Moreover, a kinetic analysis at different temperatures (255 K <= T <=
      321 K) gives insight into the evolution of E(a) with the particle size. Finally,
      time-dependent powder X-ray diffraction and net magnetization confirm the FTIR
      observations. The data are interpreted within the concept of a simple two
      component model with different activation energies for structures near the
      surface of the solid and within the bulk.

PMID- 23557030
TI  - Impact of GC content on gene expression pattern in chicken.
AB  - BACKGROUND: GC content varies greatly between different genomic regions in many
      eukaryotes. In order to determine whether this organization named isochore
      organization influences gene expression patterns, the relationship between GC
      content and gene expression has been investigated in man and mouse. However, to
      date, this question is still a matter for debate. Among the avian species,
      chicken (Gallus gallus) is the best studied representative with a complete genome
      sequence. The distinctive features and organization of its sequence make it a
      good model to explore important issues in genome structure and evolution.
      METHODS: Only nuclear genes with complete information on protein-coding sequence
      with no evidence of multiple-splicing forms were included in this study. Chicken
      protein coding sequences, complete mRNA sequences (or full length cDNA
      sequences), and 5' untranslated region sequences (5' UTR) were downloaded from
      Ensembl and chicken expression data originated from a previous work. Three
      indices i.e. expression level, expression breadth and maximum expression level
      were used to measure the expression pattern of a given gene. CpG islands were
      identified using hgTables of the UCSC Genome Browser. Correlation analysis
      between variables was performed by SAS Proprietary Software Release 8.1. RESULTS:
      In chicken, the GC content of 5' UTR is significantly and positively correlated
      with expression level, expression breadth, and maximum expression level, whereas
      that of coding sequences and introns and at the third coding position are
      negatively correlated with expression level and expression breadth, and not
      correlated with maximum expression level. These significant trends are
      independent of recombination rate, chromosome size and gene density. Furthermore,
      multiple linear regression analysis indicated that GC content in genes could
      explain approximately 10% of the variation in gene expression. CONCLUSIONS: GC
      content is significantly associated with gene expression pattern and could be one
      of the important regulation factors in the chicken genome.

PMID- 23557031
TI  - Prevalence and correlates of depression among chronic kidney disease patients in
      Taiwan.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a progressive disease that causes a
      permanent impairment of renal function and premature mortality. The associated
      prognosis may result in serious psychological distress to the affected
      individual. However, there are limited data on the psychological correlates, and
      in particular depression, in Chinese CKD patients. This study aimed to examine
      the prevalence of depression, as well as the influence of other psychosocial
      factors on depression, among Taiwanese CKD patients. METHODS: We used a cross
      sectional research design to recruit 270 CKD patients who were not undergoing
      dialysis treatment at a hospital in southern Taiwan during 2011. The structured
      questionnaire used in this study gathered information on respondent demographic
      and disease characteristics, and information obtained from the Taiwanese
      Depression Questionnaire. Factors associated with depression were examined by a
      multiple logistic regression analysis. RESULTS: The crude and age-standardized
      prevalence of depression were 22.6% and 20.6%, respectively. Those who had sleep
      disturbances, reported having no religious beliefs, followed no regular exercise
      regimen, and were diagnosed with stage III or above CKD demonstrated a
      significantly higher risk of depression. CONCLUSION: Our findings are beneficial
      to healthcare providers, as they identify both the prevalence of depression and
      several of its correlates. By identifying CKD patients with a higher risk of
      depression, healthcare providers may be better able to ensure the provision of
      appropriate rehabilitation to this population.

PMID- 23557033
TI  - Antioxidant activity of Tunisian Geranium robertianum L. (Geraniaceae).
AB  - The present investigation focuses on the methanolic extract obtained from
      Geranium robertianum L. (Geraniaceae) (Herb Robert), a herbal plant used in
      traditional medicine for the treatment of human and animal diseases. The
      antioxidant capacities of the extract were evaluated using 1,1-diphenyl-2
      picrylhydrazyl radical, beta-carotene/linoleic acid and reducing power and metal
      chelating activity assays. The amount of total phenolic content, flavonoids and
      condensed tannins was very high, and the correlation between the antioxidant
      activity potential and total phenolic level of the extract was pointed out.

PMID- 23557032
TI  - Does hormonal contraception prior to in vitro fertilization (IVF) negatively
      affect oocyte yields? A pilot study.
AB  - BACKGROUND: As oral contraceptives (OCs) suppress anti-Mullerian hormone (AMH),
      and hormonal contraceptives (HCs), likely, suppress functional ovarian reserve,
      this study was initiated to determine whether HC affect oocyte yields. METHODS:
      We investigated in a retrospective cohort study 43 oocyte donors in 71 in vitro
      fertilization (IVF) cycles, evaluating anti-Mullerian hormone (AMH) and oocyte
      yields as reflections of functional ovarian reserve (OR). In 25 IVF cycles egg
      donors were on HC within one month prior to IVF, and in 46 cycles they were not.
      Donors, based on their HCs, were further subdivided into 12 with less, and 13
      with more androgenic progestins. RESULTS: While the three groups did not differ
      in age, age at menarche, BMI and AMH, oocyte yields among donors who utilized
      estrane- and gonane-derived (higher androgenic) HCs were lower 11.3 (95% CI 8.3 -
      14.3) than either donors using no HCs 16.6 (95% CI 14.7 -18.4) (P < 0.05) or
      those using anti-androgenic HCs 19.0 (95% CI 12.2-25.8) (P< 0.01). Significance
      was maintained after adjustments for the donor age and total FSH dose used in
      ovulation induction. CONCLUSIONS: Even in young oocyte donors, high androgenic OC
      exposure appears to suppress functional ovarian reserve and oocyte yields. Since
      OCs are often routinely used in preparation for IVF, such practice may require
      reevaluation. Especially in women with diminished ovarian reserve OCs, and
      especially high androgenic progestin HCs, should, likely, be avoided.

PMID- 23557034
TI  - Military doctors and deaths by torture: when a witness becomes an accessory.

PMID- 23557035
TI  - Ban the sunset? Nonpropositional content and regulation of pharmaceutical
      advertising.
AB  - The risk that direct-to-consumer advertising of prescription pharmaceuticals
      (DTCA) may increase inappropriate medicine use is well recognized. The U.S. Food
      and Drug Administration addresses this concern by subjecting DTCA content to
      strict scrutiny. Its strictures are, however, heavily focused on the explicit
      claims made in commercials, what we term their "propositional content." Yet
      research in social psychology suggests advertising employs techniques to
      influence viewers via nonpropositional content, for example, images and music. We
      argue that one such technique, evaluative conditioning, is operative in DTCA. We
      further argue that evaluative conditioning fosters unjustified beliefs about drug
      safety and efficacy, antagonising the autonomy of viewers' choices about
      advertised medicines. We conclude that current guidelines are deficient in
      failing to account for evaluative conditioning, and that more research and debate
      are needed to determine the permissibility of this and other forms of
      nonpropositional persuasion.

PMID- 23557036
TI  - Nonpropositional content in direct-to-consumer genetic testing advertisements.

PMID- 23557037
TI  - The dilemma in regulating drug advertising: propositional versus nonpropositional
      content.

PMID- 23557038
TI  - Inching toward health decision exceptionalism.

PMID- 23557039
TI  - "Will I be pretty, will I be rich?": the missing self in antidepressant
      commercials.

PMID- 23557040
TI  - Augmenting the argument against indirect medical advertising.

PMID- 23557041
TI  - Objects closer than they appear: regulating health-based advertising of food.

PMID- 23557042
TI  - Pharmaceutical "nudging"--reinterpreting the ethics of evaluative conditioning.

PMID- 23557043
TI  - Don't ban the sunset in pharmaceutical advertising if it doesn't darken the sky.

PMID- 23557044
TI  - Pharmaceutical companies: the perfect scapegoat for everything.

PMID- 23557045
TI  - The right to know your genetic parents: from open-identity gamete donation to
      routine paternity testing.
AB  - Over the years a number of countries have abolished anonymous gamete donation and
      shifted toward open-identity policies. Donor-conceived children are said to have
      a fundamental "right to know" the identity of their donor. In this article, we
      trace the arguments that underlie this claim and question its implications. We
      argue that, given the status attributed to the right to know one's gamete donor,
      it would be discriminatory not to extend this right to naturally conceived
      children with misattributed paternity. One way to facilitate this would be
      through routine paternity testing at birth. While this proposal is likely to
      raise concerns about the conflicting interests and rights of other people
      involved, we show that similar concerns apply to the context of open-identity
      gamete donation. Unless one can identify a rational basis for treating the two
      groups differently, one's stance toward both cases should be the same.

PMID- 23557046
TI  - Whose right to know? The subjectivity of mothers in mandatory paternity testing.

PMID- 23557047
TI  - Routine paternity testing: finding the right ethical paradigm.

PMID- 23557048
TI  - Of modest proposals and non-identity: a comment on the right to know your genetic
      parents.

PMID- 23557049
TI  - Genomic data disclosure: time to reassess the realities.

PMID- 23557050
TI  - Donor conception and mandatory paternity testing: the right to know and the right
      to be told.

PMID- 23557051
TI  - DNA of a family: testing social bonds and genetic ties.

PMID- 23557052
TI  - To criticize the right to know we must question the value of genetic relatedness.

PMID- 23557053
TI  - On the moral asymmetry of gametic contributions.

PMID- 23557054
TI  - Why disclosure of genetic ancestry in misattributed paternity cases should be
      treated differently from disclosure in adoption and gamete donation.

PMID- 23557055
TI  - The right to know one's genetic origin: are gamete donations and misattributed
      paternity cases alike?

PMID- 23557056
TI  - Are the new policies on hyperandrogenism in elite female athletes really out of
      bounds? Response to "out of bounds? A critique of the new policies on
      hyperandrogenism in elite female athletes".

PMID- 23557057
TI  - The Harrison Bergeron olympics.

PMID- 23557060
TI  - Response to open peer commentaries on "ban the sunset? Nonpropositional content
      and regulation of pharmaceutical advertising".

PMID- 23557061
TI  - Response to open peer commentaries on "do researchers have an obligation to
      actively look for genetic incidental findings?".

PMID- 23557062
TI  - On the right to know and the use of double standards: response to open peer
      commentaries on "the right to know your genetic parents: from open identity
      gamete donation to routine paternity testing".

PMID- 23557063
TI  - Response to open peer commentaries on "expanding access to testicular tissue
      cryopreservation: an analysis by analogy".

PMID- 23557065
TI  - Constraints influencing sports wheelchair propulsion performance and injury risk.
AB  - The Paralympic Games are the pinnacle of sport for many athletes with a
      disability. A potential issue for many wheelchair athletes is how to train hard
      to maximise performance while also reducing the risk of injuries, particularly to
      the shoulder due to the accumulation of stress placed on this joint during
      activities of daily living, training and competition. The overall purpose of this
      narrative review was to use the constraints-led approach of dynamical systems
      theory to examine how various constraints acting upon the wheelchair-user
      interface may alter hand rim wheelchair performance during sporting activities,
      and to a lesser extent, their injury risk. As we found no studies involving
      Paralympic athletes that have directly utilised the dynamical systems approach to
      interpret their data, we have used this approach to select some potential
      constraints and discussed how they may alter wheelchair performance and/or injury
      risk. Organism constraints examined included player classifications, wheelchair
      setup, training and intrinsic injury risk factors. Task constraints examined the
      influence of velocity and types of locomotion (court sports vs racing) in
      wheelchair propulsion, while environmental constraints focused on forces that
      tend to oppose motion such as friction and surface inclination. Finally, the
      ecological validity of the research studies assessing wheelchair propulsion was
      critiqued prior to recommendations for practice and future research being given.

PMID- 23557064
TI  - Phosphodiesterase 4-targeted treatments for autoimmune diseases.
AB  - Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in
      recent years for treating patients with a variety of autoimmune diseases. This
      review summarizes the development of PDE4 inhibitors and the associated
      literature with a focus on treatments for autoimmune diseases. After the initial
      investigations of the prototypic PDE inhibitor, rolipram, more selective
      inhibitors targeting the PDE4 isozyme have been developed. With phase II and
      phase III clinical trials currently underway to evaluate the safety and efficacy
      of the latest generation of PDE4 inhibitors, namely apremilast, a new class of
      treatments may be around the corner for patients suffering from chronic,
      autoimmune diseases.

PMID- 23557066
TI  - Identification of function and mechanistic insights of guanine deaminase from
      Nitrosomonas europaea: role of the C-terminal loop in catalysis.
AB  - NE0047 from Nitrosomonas europaea has been annotated as a zinc-dependent
      deaminase; however, the substrate specificity is unknown because of the low level
      of structural similarity and sequence identity compared to other family members.
      In this study, the function of NE0047 was established as a guanine deaminase
      (catalytic efficiency of 1.2 * 10(5) M(-1) s(-1)), exhibiting secondary activity
      towards ammeline. The structure of NE0047 in the presence of the substrate
      analogue 8-azaguanine was also determined to a resolution of 1.9 A. NE0047
      crystallized as a homodimer in an asymmetric unit. It was found that the extreme
      nine-amino acid C-terminal loop forms an active site flap; in one monomer, the
      flap is in the closed conformation and in the other in the open conformation with
      this loop region exposed to the solvent. Calorimetric data obtained using the
      full-length version of the enzyme fit to a sequential binding model, thus
      supporting a cooperative mode of ligand occupancy. In contrast, the mutant form
      of the enzyme (DeltaC) with the deletion of the extreme nine amino acids follows
      an independent model of ligand occupancy. In addition, the DeltaC mutant also
      does not exhibit any enzyme activity. Therefore, we propose that the progress of
      the reaction is communicated via changes in the conformation of the C-terminal
      flap and the closed form of the enzyme is the catalytically active form, while
      the open form allows for product release. The catalytic mechanism of deamination
      was also investigated, and we found that the mutagenesis of the highly conserved
      active site residues Glu79 and Glu143 resulted in a complete loss of activity and
      concluded that they facilitate the reaction by serving as proton shuttles. 

PMID- 23557067
TI  - Effect of L-arginine on HSP70 expression in liver in weanling piglets.
AB  - BACKGROUND: This study was conducted to evaluate the effects of L-arginine (Arg)
      on photomicrographs and HSP70 expression in the liver of weanling piglets. Twelve
      healthy Landrace * Yorkshire piglets that had been weaned at 21 d (average body
      weight 5.56 +/- 0.51 kg) were randomly divided into a control group and an Arg
      group (6 g/kg feed). At age 28 d, all of the piglets were slaughtered to obtain
      liver samples to determine HSP70 expression by real-time PCR, western blot and
      immunohistochemistry. RESULTS: The results showed that, compared to control
      piglets, treatment with Arg decreased inflammatory reactions caused by weaning.
      The immunohistochemical localization of HSP70 in liver revealed strong expression
      in the Arg group. Arg increased HSP70 mRNA and HSP70 expression in the liver (P <
      0.05). CONCLUSIONS: These findings suggest that dietary supplementation with Arg
      could maintain liver health by inducing HSP70 expression in weanling piglets.

PMID- 23557068
TI  - The effect of udenafil on the hemodynamics of healthy male volunteers
      administered tamsulosin.
AB  - OBJECTIVE: The purpose of this study is to evaluate the hemodynamic interactions
      between udenafil and tamsulosin. METHODS: After a placebo lead-in period, 27
      healthy volunteers received 200 mg udenafil + tamsulosin placebo, udenafil
      placebo +0.4 mg tamsulosin, or 200 mg udenafil +0.4 mg tamsulosin. Blood pressure
      and pulse rate (PR) were measured at 15 time points from 0 to 24 hours. RESULTS:
      A single dose of udenafil, when administered with multiple tamsulosin doses,
      produced statistically significant increases in PR (mean: 10.7; 95% confidence
      interval: 5.3, 16.2 bpm; p < 0.001) compared with tamsulosin administered with an
      udenafil placebo. Systolic and diastolic blood pressure measurements remained
      unchanged. Two subjects who took udenafil with tamsulosin had a decrease in
      standing systolic blood pressure (SBP) greater than 30 mmHg in comparison to
      their baseline SBP; however, compared with the frequency of a decrease in
      standing SBP greater than 30 mmHg in comparison to the baseline, there was no
      significant difference in frequency among the four treatments (p = 0.243). There
      was no difference in the Cmax, AUClast, or AUCinf of udenafil and its active
      metabolite DA-8164 between the administration of udenafil and udenafil with
      tamsulosin. CONCLUSION: The coadministration of udenafil and tamsulosin was not
      associated with clinically significant hemodynamic changes in healthy volunteers.
      Although this study was conducted on a small number of healthy young subjects,
      the use of udenafil for the treatment of erectile dysfunction in patients taking
      tamsulosin for the treatment of benign prostatic hyperplasia is not expected to
      cause significant safety problems.

PMID- 23557070
TI  - Contact dermatitis caused by Indian marking nut juice used to relieve ankle pain.

PMID- 23557069
TI  - How to define responders in osteoarthritis.
AB  - BACKGROUND: Osteoarthritis is a clinical syndrome of failure of the joint
      accompanied by varying degrees of joint pain, functional limitation, and reduced
      quality of life due to deterioration of articular cartilage and involvement of
      other joint structures. SCOPE: Regulatory agencies require relevant clinical
      benefit on symptoms and structure modification for registration of a new therapy
      as a disease-modifying osteoarthritis drug (DMOAD). An international Working
      Group of the European Society on Clinical and Economic Aspects of Osteoporosis
      and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened
      to explore the current burden of osteoarthritis, review current regulatory
      guidelines for the conduct of clinical trials, and examine the concept of
      responder analyses for improving drug evaluation in osteoarthritis. FINDINGS: The
      ESCEO considers that the major challenges in DMOAD development are the absence of
      a precise definition of the disease, particularly in the early stages, and the
      lack of consensus on how to detect structural changes and link them to clinically
      meaningful endpoints. Responder criteria should help identify progression of
      disease and be clinically meaningful. The ideal criterion should be sensitive to
      change over time and should predict disease progression and outcomes such as
      joint replacement. CONCLUSION: The ESCEO considers that, for knee osteoarthritis,
      clinical trial data indicate that radiographic joint space narrowing >0.5 mm over
      2 or 3 years might be a reliable surrogate measure for total joint replacement.
      On-going research using techniques such as magnetic resonance imaging and
      biochemical markers may allow the identification of these patients earlier in the
      disease process.

PMID- 23557071
TI  - Prevalence and plasmid characterization of the qnrD determinant in
      Enterobacteriaceae isolated from animals, retail meat products, and humans.
AB  - qnrD, unlike other qnr genes, is mainly located on small nonconjugative plasmids.
      We investigated the presence of qnrD among 1,373 Enterobacteriaceae isolates in
      China. Twelve qnrD-positive strains were detected, and all were nonsusceptible to
      fluoroquinolones. The complete sequence of plasmids showed that the qnrD
      determinants were located on two plasmids with a respective size of ~4.2 and 2.7
      k-bp. Interestingly, the identification of qnrD in this study revealed the
      highest prevalence of Proteeae among Enterobacteriaceae identified.

PMID- 23557072
TI  - Novel BCOR mutations in patients with oculofaciocardiodental (OFCD) syndrome.

PMID- 23557074
TI  - Interleukin-4RA gene polymorphism is associated with oral mucous membrane
      pemphigoid.
AB  - OBJECTIVE: The aim of this study was to analyse whether the polymorphisms of
      several pro- and anti-inflammatory cytokines may influence the susceptibility to
      predominantly oral Mucous membrane pemphigoid (MMP) in a Northern Italian
      population. MATERIAL AND METHODS: DNA was obtained from 41 MMP patients (29 with
      exclusively oral pemphigoid [OP]) and 140 unrelated bone marrow donors. Thirteen
      cytokine genes with 22 single-nucleotide polymorphisms (SNP) were studied by a
      sequence-specific PCR assay. RESULTS: There was no significant difference between
      the patients taken together and healthy controls for any cytokine gene
      polymorphism studied. However, the allele A of the IL-4 receptor A (IL-4RA) was
      significantly more frequent in OP than controls (P < 0.05), causing an increased
      frequency of genotype A/A in OP patients (89.7 vs. 67.9, odds ratio: 4.11, 95%
      confidence intervals 1.18-14.28, P = 0.023, Pc = 0.046). CONCLUSION: IL-4RA-1902
      A/A genotype has been associated with a reduced response to IL-4 and has been
      found in 90% OP patient. Giving the supposed importance of IL-4 in MMP fibrotic
      process, our results can partially explain the low likelihood of scarring in OP
      patients.

PMID- 23557073
TI  - The association of gout with sleep disorders: a cross-sectional study in primary
      care.
AB  - BACKGROUND: Both gout and sleep apnoea are associated with the metabolic
      syndrome. Hyperuricaemia is also prevalent in sleep apnoea syndrome. The
      objective of this study was to examine the association between gout and sleep
      apnoea and other sleep disorders. METHODS: Data were taken from a validated
      database of general practice records from nine practices in the UK between 2001
      and 2008. People consulting for gout were identified via Read codes and each
      matched with four controls for age, gender, practice and year of gout
      consultation. Sleep problems and confounding comorbidities were also identified
      via Read codes. Medications were identified through a linked database of
      prescription records. The association between gout and sleep disorders was
      assessed using a logistic regression model, adjusting for ischaemic heart
      disease, hypertension, diabetes mellitus and diuretic use. RESULTS: 1689
      individuals with gout were identified and each successfully matched to four
      controls. Amongst those with gout, the prevalence of any sleep problem was 4.9%,
      sleep problems other than sleep apnoea 4.2%, and sleep apnoea 0.7%, compared to
      3.5%, 3.2% and 0.3% respectively in controls. Gout was associated with any sleep
      problem (odds ratio (OR) 1.44; 95% confidence interval (CI) 1.11, 1.87), sleep
      problems other than sleep apnoea (OR 1.36; 95% CI 1.03, 1.80), and sleep apnoea
      (OR 2.10; 95% CI 1.01, 4.39). On multivariable analysis, gout remained
      significantly associated with any sleep problem (OR 1.39; 95% CI 1.06, 1.81) and
      sleep problems other than sleep apnoea (OR 1.37; 95% CI 1.03, 1.82), however the
      association with sleep apnoea was attenuated (OR 1.48, 95% CI 0.70, 3.14).
      CONCLUSIONS: Gout and sleep problems appear to be associated and clinicians
      should be aware of the co-existence of these two conditions. Larger prospective
      epidemiological studies are required to explore causality.

PMID- 23557075
TI  - A macromolecular trafficking complex composed of beta2-adrenergic receptors, A
      Kinase Anchoring Proteins and L-type calcium channels.
AB  - Abstract Sympathetic modulation of cardiac L-type calcium channels is an
      important mechanism for regulating heart rate and cardiac contractility. At the
      molecular level, activation of beta-adrenergic receptors (betaAR) increases
      calcium influx into cardiac myocytes by activating protein kinase A (PKA),
      leading to subsequent phosphorylation of L-type calcium channels. In the case of
      the beta2AR, this process is facilitated by the presence of A-Kinase Anchoring
      Proteins (AKAPs) that serve as scaffolding proteins for the L-type calcium
      channel and the beta2AR complex. Our work has shown that, in addition to
      facilitating PKA phosphorylation of the channel, AKAPs also promote an increase
      in the Cav1.2 channel surface expression. Here we review the molecular mechanisms
      of beta2AR/AKAP/L-type channel interactions and trafficking.

PMID- 23557076
TI  - Droplet detachment by air flow for microstructured superhydrophobic surfaces.
AB  - Quantitative correlation between critical air velocity and roughness of
      microstructured surface has still not been established systematically until the
      present; the dynamics of water droplet detachment by air flow from micropillar
      like superhydrophobic surfaces is investigated by combining experiments and
      simulation comparisons. Experimental evidence demonstrates that the onset of
      water droplet detachment from horizontal micropillar-like superhydrophobic
      surfaces under air flow always starts with detachment of the rear contact lines
      of the droplets from the pillar tops, which exhibits a similar dynamic mechanism
      for water droplet motion under a gravity field. On the basis of theoretical
      analysis and numerical simulation, an explicit analytical model is proposed for
      investigating the detaching mechanism, in which the critical air velocity can be
      fully determined by several intrinsic parameters: water-solid interface area
      fraction, droplet volume, and Young's contact angle. This model gives predictions
      of the critical detachment velocity of air flow that agree well with the
      experimental measurements.

PMID- 23557077
TI  - Superior glycaemic control with once-daily insulin degludec/insulin aspart versus
      insulin glargine in Japanese adults with type 2 diabetes inadequately controlled
      with oral drugs: a randomized, controlled phase 3 trial.
AB  - AIMS: This phase 3, 26-week, open-label, treat-to-target trial investigated the
      efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in insulin-naive
      Japanese adults with type 2 diabetes. METHODS: Subjects were randomized to once
      daily injections of IDegAsp (n = 147) or insulin glargine (IGlar) (n = 149), both
      +/-<=2 oral antidiabetic treatments. IDegAsp was given before the largest meal at
      the discretion of each subject (and maintained throughout the trial); IGlar was
      dosed according to label. Both insulins were titrated to a target prebreakfast
      self-measured plasma glucose of 3.9 to <5.0 mmol/l. RESULTS: After 26 weeks, mean
      HbA1c was 7% with IDegAsp and 7.3% with IGlar; superiority of IDegAsp to IGlar
      was shown (estimated treatment difference, ETD; IDegAsp-IGlar: -0.28% points [
      0.46; -0.10](95% CI), p < 0.01). At end-of-trial, mean fasting plasma glucose
      (FPG) was similar for IDegAsp and IGlar (5.7 vs. 5.6 mmol/l; ETD IDegAsp-IGlar:
      0.15 mmol/l [-0.29; 0.60](95% CI), p = NS). IDegAsp was associated with
      numerically lower rates of overall confirmed (27%) and nocturnal confirmed
      hypoglycaemia (25%) versus IGlar (estimated rate ratio IDegAsp/IGlar: 0.73 [0.50;
      1.08](95% CI), p = NS, and 0.75 [0.34; 1.64](95% CI), p = NS, respectively). Mean
      daily insulin doses were similar between groups at end-of-trial (both: 0.41 U/kg)
      as were the increases in body weight from baseline (both: 0.7 kg). Adverse event
      profiles were similar between groups. CONCLUSIONS: IDegAsp provided superior long
      term glycaemic control compared to IGlar, with similar FPG and doses and
      numerically lower rates of overall and nocturnal hypoglycaemia (p = NS).

PMID- 23557079
TI  - The Journal of Dermatology. Greetings from the new Editor-in-Chief.

PMID- 23557078
TI  - Impact of persistent, frequent regurgitation on quality of life in heartburn
      responders treated with acid suppression: a multinational primary care study.
AB  - BACKGROUND: In gastro-oesophageal reflux disease (GERD), heartburn responds well
      to acid suppression, but regurgitation is a common cause of incomplete treatment
      response. AIM: To assess the prevalence and burden of persistent, frequent
      regurgitation in primary care patients with GERD treated with acid suppression.
      METHODS: We analysed observational data from 134 sites across six European
      countries in patients diagnosed with GERD. Within 3 months of the index visit,
      symptoms were assessed using the Reflux Disease Questionnaire, and their impact
      on sleep and work productivity with the Quality of Life in Reflux and Dyspepsia
      questionnaire and the Work Productivity and Activity Impairment Questionnaire,
      respectively. Patients provided information on concomitant over-the-counter (OTC)
      GERD medication use. RESULTS: Persistent, frequent (3-7 days/week) regurgitation
      was reported by 13.2% (153/1156) of GERD patients with no heartburn on acid
      suppression; the prevalence was very similar for patients with up to 2 days/week
      of ongoing mild heartburn. Among patients without heartburn, sleep disturbance of
      any type was reported by 50.7-60.1% with persistent, frequent regurgitation,
      compared with 38.1-51.1% and 14.4-19.2% of those with less frequent or no
      regurgitation respectively. Persistent, frequent regurgitation was associated
      with increased use of OTC medication and more hours of work missed, whether mild,
      infrequent heartburn was present or not. CONCLUSIONS: Frequent regurgitation,
      which persisted in 12-13% of patients with no or infrequent, mild heartburn on
      acid suppression, negatively affected sleep and work productivity, and increased
      use of OTC medication. Persistent, frequent regurgitation is problematic for
      primary care patients with GERD.

PMID- 23557080
TI  - Differentiated markers in undifferentiated cells: expression of smooth muscle
      contractile proteins in multipotent bone marrow mesenchymal stem cells.
AB  - In studying the differentiation of stem cells along smooth muscle lineage, smooth
      muscle cell (SMC) contractile proteins serve as markers for the relative state of
      maturation. Yet, recent evidence suggests that some SMC markers are probably
      expressed in multipotent mesenchymal stem cells (MSCs). Such a paradox
      necessitates investigations to re-examine their role as differentiated markers in
      MSCs. We tried to detect the expression of four widely used SMC markers including
      alpha-smooth muscle actin (alpha-SMA), h1-calponin, desmin and smooth muscle
      myosin heavy chain (SM-MHC), as well as the other isoforms of calponin family in
      resting MSCs. Then we used three different conditions to initiate MSCs
      differentiation along SMC lineage, and examined the alternation of SMC markers
      expression at both the transcript level and protein level. Desmin and h1-calponin
      are expressed in MSCs, in the presence or absence of SMC induction conditions.
      Moreover, MSCs are shown to express all known isoforms of calponin. Double
      staining reveals that h1-calponin +/alpha-SMA - cells constitute the majority of
      resting MSCs. Under differentiated conditions, expression of SM-MHC was initiated
      and expression of alpha-SMA was promoted. The expression of SM-MHC and
      upregulation of alpha-SMA are relatively reliable indications of a mature smooth
      muscle phenotype in MSCs. Given that the cells are particularly rich in calponins
      expression, we postulate possible roles of these proteins in regulating cellular
      function by taking part in actin cytoskeleton and signaling. These findings imply
      that an extensive study of the cell physiology of MSCs should focus on the
      functional roles for these proteins, rather than simply regard them as
      differentiated markers.

PMID- 23557081
TI  - Opening communication channels with people living with HIV using mobile phone
      text messaging: insights from the CAMPS trial.
AB  - BACKGROUND: Using two-way mobile phone text messages to improve adherence to
      antiretroviral medication enhances communication between patients and health
      workers. We describe the implications of participants' responses to text messages
      in the Cameroon Mobile Phone SMS (CAMPS) trial. FINDINGS: This is a cross
      sectional analysis of data from the intervention arm of the CAMPS trial. CAMPS
      was a randomized controlled trial of motivational text messaging versus usual
      care to improve adherence to antiretroviral medication among people living with
      HIV in Yaounde, Cameroon (n = 200) over a 6 month period. Participants in the
      intervention arm (n = 101) were given a contact phone number, but were not
      required to respond to their reminder messages. If they did, their responses were
      noted and reported as counts and percentages. We received 99 phone calls and 55
      text messages (154 responses) from 48 participants during the study period. The
      median number of responses was 1 (first quartile [Q1]: 1; third quartile [Q3]:
      3). Half (n = 79, 51.1%) of them were expressions of gratitude. The rest included
      requests for logistical (n = 21, 13.6%), medical (n = 20, 12.9%) and financial (n
      = 11, 7.1%) support. CONCLUSION: Initiating two-way mobile communication opens
      more channels for people living with HIV to express unmet needs. Researchers,
      policy makers and clinicians should be ready to respond to the needs expressed by
      patients who respond to text messages. TRIAL REGISTRATION: Pan-African Clinical
      Trials Registry: PACTR201011000261458;

PMID- 23557082
TI  - Helping the decision maker effectively promote various experts' views into
      various optimal solutions to China's institutional problem of health care
      provider selection through the organization of a pilot health care provider
      research system.
AB  - BACKGROUND: The main aim of China's Health Care System Reform was to help the
      decision maker find the optimal solution to China's institutional problem of
      health care provider selection. A pilot health care provider research system was
      recently organized in China's health care system, and it could efficiently
      collect the data for determining the optimal solution to China's institutional
      problem of health care provider selection from various experts, then the purpose
      of this study was to apply the optimal implementation methodology to help the
      decision maker effectively promote various experts' views into various optimal
      solutions to this problem under the support of this pilot system. METHODS: After
      the general framework of China's institutional problem of health care provider
      selection was established, this study collaborated with the National Bureau of
      Statistics of China to commission a large-scale 2009 to 2010 national expert
      survey (n = 3,914) through the organization of a pilot health care provider
      research system for the first time in China, and the analytic network process
      (ANP) implementation methodology was adopted to analyze the dataset from this
      survey. RESULTS: The market-oriented health care provider approach was the
      optimal solution to China's institutional problem of health care provider
      selection from the doctors' point of view; the traditional government's
      regulation-oriented health care provider approach was the optimal solution to
      China's institutional problem of health care provider selection from the
      pharmacists' point of view, the hospital administrators' point of view, and the
      point of view of health officials in health administration departments; the
      public private partnership (PPP) approach was the optimal solution to China's
      institutional problem of health care provider selection from the nurses' point of
      view, the point of view of officials in medical insurance agencies, and the
      health care researchers' point of view. CONCLUSIONS: The data collected through a
      pilot health care provider research system in the 2009 to 2010 national expert
      survey could help the decision maker effectively promote various experts' views
      into various optimal solutions to China's institutional problem of health care
      provider selection.

PMID- 23557083
TI  - Pan-BH3 mimetic S1 exhibits broad-spectrum antitumour effects by cooperation
      between Bax and Bak.
AB  - Small molecule S1 is a pan-BH3 mimetic that can bind antiapoptotic Bcl-2, Bcl-xL
      and Mcl-1 proteins. Herein, different Bcl-2 member expression cancer cell lines
      (NCI-H345, MCF-7, SMMC-7721 and Hela) and cells deficient in Bax and/or Bak by
      shRNA were used to unravel the cascade of events by which S1 promotes apoptosis
      compared with Bcl-2/Bcl-xL inhibitor ABT-737. We identified that S1 exhibited
      broader antitumour spectrum than ABT-737 through disruption of more Bcl-2
      interactions including Mcl-1/Bak interaction. Moreover, the individual and
      combined roles of Bax and Bak in S1-induced apoptosis were revealed. Our results
      showed that S1 induced a Bak-mediated apoptosis. Bak played a predominant role in
      either S1 or ABT-737-induced apoptosis through the cooperation with Bax on the
      formation of large oligomers on mitochondrial membrane. 

PMID- 23557085
TI  - Type of arteriovenous vascular access and association with patency and mortality.
AB  - BACKGROUND: There are only a few risk factors known for primary patency loss in
      patients with an arteriovenous graft or fistula. Furthermore, a limited number of
      studies have investigated the association between arteriovenous access modality
      and primary patency loss and mortality. The aim of this study was to investigate
      risk factors for patency loss and to investigate the association between graft
      versus fistula use and outcomes (patency loss and mortality). METHODS: We
      prospectively followed 919 incident hemodialysis patients and calculated hazard
      ratios (HRs) for putative risk factors of primary patency loss using Cox
      regression. Furthermore, HRs were calculated to study the association between
      graft versus fistula use and two-year primary patency loss and two-year
      mortality. RESULTS: Cardiovascular disease, prior catheter use, lowest tertile of
      albumin, highest tertile of hsCRP, and lowest tertile of fetuin-A were associated
      with primary patency loss in both patients with grafts and fistulas. Increased
      age, female sex, and diabetes mellitus were only associated with primary patency
      loss in patients with a fistula. We did not observe an association between
      primary patency loss and BMI, residual GFR, levels of calcium, phosphorus, and
      total cholesterol. Furthermore, graft use as compared with fistula use was
      associated with an 1.4-fold (95% CI 1.0-1.9) increased risk of primary patency
      loss and with an 1.5-fold(95% CI 1.0-2.2) increased mortality risk. CONCLUSION:
      Cardiovascular disease, prior catheter use, albumin, hsCRP, and fetuin-A are risk
      factors for patency loss. Graft use as compared with fistula use was associated
      with an increased risk of patency loss and mortality.

PMID- 23557084
TI  - 'Use what God has given me': difference and disparity in breast reconstruction.
AB  - African-American women are significantly less likely to undergo postmastectomy
      breast reconstruction compared to white women in the USA. These observed
      differences have been interpreted as evidence of a healthcare disparity. The
      current study examines breast reconstruction decision-making among African
      American women, locating reconstruction decisions in a context of culture, racial
      inequality and biomedicalisation. Semi-structured interviews were conducted with
      27 African-American women who underwent mastectomy for breast cancer to add
      patient-centred perspectives to existing conceptualisations of racial/ethnic
      differences in reconstruction. Participants were socio-demographically diverse,
      and resided in the New York metropolitan area. Data analysis was informed by
      grounded theory. Spiritually and culturally informed body ethics often guided
      surgery decisions. Participants expressed reservations about breast implants,
      preferring autologous procedures that use 'what God has given'. For some, breast
      reconstruction restored a sense of normalcy after cancer; others challenged an
      imperative to reconstruct. Several participants redirected our focus on access to
      reconstruction toward access to alternatives, noting the low reimbursement for
      prostheses, or their unavailability in patients' skin tones. We suggest that a
      framework of 'stratified biomedicalization' better addresses the complexities of
      race, class and gender that inform preference, access and recommendations for
      breast reconstruction, and focuses attention on access to high and low-tech
      interventions. 

PMID- 23557086
TI  - PASTA: splice junction identification from RNA-sequencing data.
AB  - BACKGROUND: Next generation transcriptome sequencing (RNA-Seq) is emerging as a
      powerful experimental tool for the study of alternative splicing and its
      regulation, but requires ad-hoc analysis methods and tools. PASTA (Patterned
      Alignments for Splicing and Transcriptome Analysis) is a splice junction
      detection algorithm specifically designed for RNA-Seq data, relying on a highly
      accurate alignment strategy and on a combination of heuristic and statistical
      methods to identify exon-intron junctions with high accuracy. RESULTS:
      Comparisons against TopHat and other splice junction prediction software on real
      and simulated datasets show that PASTA exhibits high specificity and sensitivity,
      especially at lower coverage levels. Moreover, PASTA is highly configurable and
      flexible, and can therefore be applied in a wide range of analysis scenarios: it
      is able to handle both single-end and paired-end reads, it does not rely on the
      presence of canonical splicing signals, and it uses organism-specific regression
      models to accurately identify junctions. CONCLUSIONS: PASTA is a highly efficient
      and sensitive tool to identify splicing junctions from RNA-Seq data. Compared to
      similar programs, it has the ability to identify a higher number of real splicing
      junctions, and provides highly annotated output files containing detailed
      information about their location and characteristics. Accurate junction data in
      turn facilitates the reconstruction of the splicing isoforms and the analysis of
      their expression levels, which will be performed by the remaining modules of the
      PASTA pipeline, still under development. Use of PASTA can therefore enable the
      large-scale investigation of transcription and alternative splicing.

PMID- 23557087
TI  - Phase progression of gamma-Al2O3 nanoparticles synthesized in a solvent-deficient
      environment.
AB  - Our simple and uniquely cost-effective solvent-deficient synthetic method
      produces 3-5 nm Al2O3 nanoparticles which show promise as improved industrial
      catalyst-supports. While catalytic applications are sensitive to the details of
      the atomic structure, a diffraction analysis of alumina nanoparticles is
      challenging because of extreme size/microstrain-related peak broadening and the
      similarity of the diffraction patterns of various transitional Al2O3 phases.
      Here, we employ a combination of X-ray pair-distribution function (PDF) and
      Rietveld methods, together with solid-state NMR and thermogravimetry/differential
      thermal analysis-mass spectrometry (TG/DTA-MS), to characterize the alumina phase
      progression in our nanoparticles as a function of calcination temperature between
      300 and 1200  degrees C. In the solvent-deficient synthetic environment, a
      boehmite precursor phase forms which transitions to gamma-Al2O3 at an
      extraordinarily low temperature (below 300  degrees C), but this gamma-Al2O3 is
      initially riddled with boehmite-like stacking-fault defects that steadily
      disappear during calcination in the range from 300 to 950  degrees C. The healing
      of these defects accounts for many of the most interesting and widely reported
      properties of the gamma-phase.

PMID- 23557088
TI  - Prevention strategies to reduce falls in psychiatric settings.
AB  - A Fall Committee was developed in response to an increase in the rate of falls by
      patients at a primarily behavioral health, urban teaching hospital in the mid
      Atlantic region of the United States. The Fall Committee identified interventions
      to potentially lessen the number of patient falls and areas where documentation
      could be improved to better describe an incident in the medical record. The Fall
      Committee developed paperwork to be completed after each patient fall and made
      changes to the low fall risk and high fall risk treatment plans. This article
      describes the recommendations submitted by the Fall Committee and its subsequent
      implementation. Although not causational, the fall rate decreased after the
      recommendations of the Fall Committee were implemented; however, a recent rise in
      the fall rate was noted and attributed to higher patient acuity on the unit. The
      committee investigation into this issue highlighted the paucity of research in
      this field and the need for a streamlined, easy-to-use, behavioral health fall
      scale to more accurately judge the fall risk of patients in this specialized
      subset.

PMID- 23557089
TI  - Consulting with a surgeon before breast cancer surgery: patient question asking
      and satisfaction.
AB  - Research has found a negative association between patient question asking and
      aspects of their satisfaction. In the context of surgical oncology, the aim of
      this exploratory study was to test the association between patient question
      asking and 3 indices of their satisfaction. Participants included 51 women who
      were newly diagnosed with breast cancer engaged in presurgical consultations with
      a surgical oncologist from a National Cancer Institute-designated cancer center
      in the Northeastern United States. Outcomes were patients' postconsultation
      reports of their satisfaction with the treatment plan, intentions to adhere to
      the treatment plan, and satisfaction with the surgeon. The main predictor was the
      frequency of patients' self-initiated questions coded from videotapes of
      consultations. The frequency of patients' self-initiated questions was negatively
      associated with their satisfaction with the treatment plan (p = .02), intentions
      to adhere to the treatment plan (p = .02), and satisfaction with the surgeon (p =
      .07). Results can be explained in terms of patients' perceptions that the
      surgeon's information was insufficient or inadequate. Future research needs to
      identify the specific content of patients' questions and how such content might
      be associated with satisfaction. 

PMID- 23557090
TI  - Associations between selected immune-mediated diseases and tuberculosis: record
      linkage studies.
AB  - BACKGROUND: Previous studies have suggested that there may be an association
      between some immune-mediated diseases and risk of tuberculosis (TB). METHODS: We
      analyzed a database of linked statistical records of hospital admissions and
      death certificates for the whole of England (1999 to 2011), and a similar
      database (the Oxford Record Linkage Study (ORLS)) for a region of southern
      England in an earlier period. Rate ratios for TB were determined, comparing
      immune-mediated disease cohorts with comparison cohorts. RESULTS: In the all
      England dataset, there were significantly elevated risks of TB after hospital
      admission for the following individual immune-mediated diseases: Addison's
      disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active
      hepatitis, coeliac disease, Crohn's disease, dermatomyositis, Goodpasture's
      syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia purpura (ITP),
      myasthenia gravis, myxedema, pemphigoid, pernicious anemia, polyarteritis nodosa,
      polymyositis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis,
      scleroderma, Sjogren's syndrome, systemic lupus erythematosus (SLE),
      thyrotoxicosis and ulcerative colitis. Particularly high levels of risk were
      found for Addison's disease (rate ratio (RR) = 11.9 (95% CI 9.5 to 14.7)),
      Goodpasture's syndrome (RR = 10.8 (95% CI 4.0 to 23.5)), SLE (RR = 9.4 (95% CI
      7.9 to 11.1)), polymyositis (RR = 8.0 (95% CI 4.9 to 12.2)), polyarteritis nodosa
      (RR = 6.7 (95% CI 3.2 to 12.4)), dermatomyositis (RR = 6.6 (95% CI 3.0 to 12.5)),
      scleroderma (RR = 6.1 (95% CI 4.4 to 8.2)) and autoimmune hemolytic anemia (RR =
      5.1 (95% CI 3.4 to 7.4)). CONCLUSIONS: These two databases show that patients
      with some immune-mediated diseases have an increased risk of TB, although we
      cannot explicitly state the direction of risk or exclude confounding. Further
      study of these associations is warranted, and these findings may aid TB
      screening, control and treatment policies.

PMID- 23557091
TI  - A case report of semitendinosus tendon autograft for reconstruction of the
      meniscal wall supporting a collagen implant.
AB  - PURPOSE: Describe the evolution of the reconstruction of meniscal rim with
      semitendinosus tendon in a patient with knee pain after a subtotal meniscectomy
      and absence of meniscal wall. METHOD: 32 years old male with a six-month history
      of the left knee pain after a subtotal meniscectomy. The MRI indicated a small
      internal meniscal remainder without posterior horn attachment. Taking this
      absence as a relative contraindication for implant and meniscal transplantation,
      the reconstruction of a new meniscal wall with semitendinosus tendon autograft
      was considered. A collagen meniscal implant was attached to the new wall five
      months later. RESULTS: After two years the patient referred only non specific
      discomfort with full pain relief in the medial compartment. The MRI revealed
      integration of implants without significant degenerative changes compared to
      previous images. CONCLUSIONS: This staged technique was designed to restore
      medial meniscus-like biologic tissue in a symptomatic patient following
      arthroscopic subtotal meniscectomy with a significant loss of the peripheral
      meniscus rim. Symptomatic improvement was obtained at two years follow-up.

PMID- 23557092
TI  - Galactose-based amphiphilic block copolymers: synthesis, micellization, and
      bioapplication.
AB  - Redox-responsive amphiphilic diblock copolymers, poly(6-O-methacryloyl-D
      galactopyranose-co-2-(N,N-dimethylaminoethyl) methacrylate)-b-poly(pyridyl
      disulfide ethyl methylacrylate) (P(MAGP-co-DMAEMA)-b-PPDSMA) were obtained by
      deprotection of poly((6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-D
      galactopyranose)-co-DMAEMA)-b-PPDSMA [P(MAlpGP-co-DMAEMA)-b-PPDSMA], which were
      prepared via reversible addition-fragmentation chain transfer (RAFT)
      polymerization of PDSMA using P(MAlpGP-co-DMAEMA) as macro-RAFT agent. Dynamic
      light scattering (DLS) and transmission electron microscopy (TEM) studies showed
      that diblock copolymers P(MAGP-co-DMAEMA)-b-PPDSMA can self-assemble into
      micelles. Doxorubicin (DOX) could be encapsulated by P(MAGP-co-DMAEMA)-b-PPDSMA
      upon micellization and released upon adding glutathione (GSH) into the micelle
      solution. The galactose functional groups in the PMAGP block had specific
      interaction with HepG2 cells, and P(MAGP-co-DMAEMA)-b-PPDSMA can act as gene
      delivery vehicle. So, this kind of polymer has potential applications in hepatoma
      targeting drug and gene delivery and biodetection.

PMID- 23557094
TI  - Lucio's phenomenon after childbirth.

PMID- 23557095
TI  - Morphology of the transverse ligament of the atlas and the alar ligaments in the
      silver fox (Vulpes vulpes var).
AB  - BACKGROUND: Recent new anatomical and histological features of craniocervical
      junction in dogs and cats were described providing evidence of differences
      between the carnivore species. No information on these structures in foxes
      exists. RESULTS: Two parts of the alar ligaments were found. A longer one aroused
      from dens of axis to the internal (medial) surface of the occipital condyles and
      was called apical part. A shorter part originated from the entire length of the
      lateral edge of the dens of axis and terminated on the internal wall of the
      vertebral foramen of atlas and thus was called the lateral part. The transverse
      ligament of the atlas was widened in the mid region, above the dens of axis, and
      thickened at enthesis. Periosteal fibrocartilage was detected in the transverse
      ligament of the atlas at the enthesis, and sesamoid fibrocartilage was present on
      periphery in the middle of the ligament. CONCLUSIONS: The craniocervical junction
      in foxes differs in part from other carnivores such as dogs and cats but
      resembles that of mesaticephalic dogs. The sesamoid and periosteal fibrocartilage
      supports the transverse ligament of the atlas whereas the alar ligaments have no
      cartilage.

PMID- 23557093
TI  - Prevalence of orofacial clefts in Nigeria.
AB  - Orofacial clefts are the most common malformations of the head and neck. In
      Africa, orofacial clefts are underascertained, with little or no surveillance
      system in most parts for clefts and other birth defects. A Nigerian craniofacial
      anomalies study, NigeriaCRAN, was established in 2006 to support cleft research
      specifically for epidemiological studies, treatment outcomes, and studies into
      etiology and prevention. We pooled data from seven of the largest Smile Train
      treatment centers in the six geopolitical zones in Nigeria. Data from September
      2006 to June 2011 were analyzed and clefts compared between sides and genders
      using the Fisher exact test. A total of 2197 cases were identified during the
      study period, with an estimated prevalence rate of 0.5 per 1000. Of the total
      number of orofacial clefts, 54.4% occur in males and 45.6% in females. There was
      a significant difference (P = .0001) between unilateral left clefts and
      unilateral right clefts, and there was a significant difference (P = .0001)
      between bilateral clefts and clefts on either the left or right side. A
      significant gender difference (P = .03) was also observed for cleft palate, with
      more females than males. A total of 103 (4.7%) associated anomalies were
      identified. There were nine syndromic cleft cases, and 10.4% of the total number
      of individuals with clefts have an affected relative. The significant difference
      between unilateral clefts and the gender differences in the proportion of cleft
      palate only are consistent with the literature. The present study emphasizes the
      need for birth defects registries in developing countries in order to estimate
      the exact prevalence of birth defects including orofacial clefts. 

PMID- 23557096
TI  - Naturalistic assessment of executive function and everyday multitasking in
      healthy older adults.
AB  - Everyday multitasking and its cognitive correlates were investigated in an older
      adult population using a naturalistic task, the Day Out Task. Fifty older adults
      and 50 younger adults prioritized, organized, initiated, and completed a number
      of subtasks in a campus apartment to prepare for a day out (e.g., gather
      ingredients for a recipe, collect change for a bus ride). Participants also
      completed tests assessing cognitive constructs important in multitasking.
      Compared to younger adults, the older adults took longer to complete the everyday
      tasks and more poorly sequenced the subtasks. Although they initiated, completed,
      and interweaved a similar number of subtasks, the older adults demonstrated
      poorer task quality and accuracy, completing more subtasks inefficiently. For the
      older adults, reduced prospective memory abilities were predictive of poorer task
      sequencing, while executive processes and prospective memory were predictive of
      inefficiently completed subtasks. The findings suggest that executive dysfunction
      and prospective memory difficulties may contribute to the age-related decline of
      everyday multitasking abilities in healthy older adults.

PMID- 23557097
TI  - Genetic compound heterozygosity for Southeast Asian ovalocytosis and thalassemia
      in Thailand: prevalence and phenotypic analysis.

PMID- 23557098
TI  - Minimally invasive reconstruction of lateral tibial plateau fractures using the
      jail technique: a biomechanical study.
AB  - BACKGROUND: This study described a novel, minimally invasive reconstruction
      technique of lateral tibial plateau fractures using a three-screw jail technique
      and compared it to a conventional two-screw osteosynthesis technique. The benefit
      of an additional screw implanted in the proximal tibia from the anterior at an
      angle of 90 degrees  below the conventional two-screw reconstruction after
      lateral tibial plateau fracture was evaluated. This new method was called the
      jail technique. METHODS: The two reconstruction techniques were tested using a
      porcine model (n = 40). Fracture was simulated using a defined osteotomy of the
      lateral tibial plateau. Load-to-failure and multiple cyclic loading tests were
      conducted using a material testing machine. Twenty tibias were used for each
      reconstruction technique, ten of which were loaded in a load-to-failure protocol
      and ten cyclically loaded (5000 times) between 200 and 1000 N using a ramp
      protocol. Displacement, stiffness and yield load were determined from the
      resulting load displacement curve. Failure was macroscopically documented.
      RESULTS: In the load-to-failure testing, the jail technique showed a
      significantly higher mean maximum load (2275.9 N) in comparison to the
      conventional reconstruction (1796.5 N, p < 0.001). The trend for better outcomes
      for the novel technique in terms of stiffness and yield load did not reach
      statistical significance (p > 0.05). In cyclic testing, the jail technique also
      showed better trends in displacement that were not statistically significant.
      Failure modes showed a tendency of screws cutting through the bone (cut-out) in
      the conventional reconstruction. No cut-out but a bending of the lag screws at
      the site of the additional third screw was observed in the jail technique.
      CONCLUSIONS: The results of this study indicate that the jail and the
      conventional technique have seemingly similar biomechanical properties. This
      suggests that the jail technique may be a feasible alternative to conventional
      screw osteosynthesis in the minimally invasive reconstruction of lateral tibial
      plateau fractures. A potential advantage of the jail technique is the prevention
      of screw cut-outs through the cancellous bone.

PMID- 23557099
TI  - Investigation of an electrochemically switched heterocyclization reaction on gold
      surface.
AB  - We report an investigation of an electrochemically switched heterocyclization
      reaction on hydroquinone-terminated self-assembled monolayers (SAMs). This
      reaction involves an electrochemically modulated hydroquinone/benzoquinone
      transformation step in the SAMs and a subsequent heterocyclization step taking
      place between the electrochemically generated benzoquinone moieties in SAMs and l
      cysteine in solution. The reaction process was monitored by XPS and
      electrochemical surface-enhanced Raman spectroscopy (EC-SERS). The surface
      reaction proceeds as a two-step reaction to give a benzothiazine product, which
      is in contrast to the much more complicated multiple step reactions in solution.
      This result suggests that the tight molecular packing in the SAMs does not hinder
      the intramolecular heterocylization reaction, but prevents the intermolecular
      coupling reaction from happening. This work provides insights to the control and
      detection of biomolecule related multistep reactions occurring at solid-liquid
      interface.

PMID- 23557100
TI  - Self-correction of chromosomal abnormalities in human preimplantation embryos and
      embryonic stem cells.
AB  - Aneuploidy is commonly seen in human preimplantation embryos, most particularly
      at the cleavage stage because of genome activation by third cell division.
      Aneuploid embryos have been used for the derivation of normal embryonic stem cell
      (ESC) lines and developmental modeling. This review addresses aneuploidies in
      human preimplantation embryos and human ESCs and the potential of self-correction
      of these aberrations. Diploid-aneuploid mosaicism is the most frequent
      abnormality observed; hence, embryos selected by preimplantation genetic
      diagnosis at the cleavage or blastocyst stage could be partly abnormal.
      Differentiation is known as the barrier for eliminating mosaic embryos by death
      and/or decreased division of abnormal cells. However, some mosaicisms, such as
      copy number variations could be compatible with live birth. Several reasons have
      been proposed for self-correction of aneuploidies during later stages of
      development, including primary misdiagnosis, allocation of the aneuploidy in the
      trophectoderm, cell growth advantage of diploid cells in mosaic embryos, lagging
      of aneuploid cell division, extrusion or duplication of an aneuploid chromosome,
      and the abundance of DNA repair gene products. Although more studies are needed
      to understand the mechanisms of self-correction as a rare phenomenon, most
      likely, it is related to overcoming mosaicism. 

PMID- 23557101
TI  - The relationship between antenatal provider type and maternal care in rural
      Ghana: a cross-sectional study.
AB  - OBJECTIVES: To investigate the influence of antenatal provider type on maternity
      care in rural Ghana. METHODS: An analysis of maternal care by antenatal provider
      type using the 2008 Ghana Demographic and Health Survey. Study population
      included rural Ghanaian women aged 15-49 years with report of a live birth
      between 2003 and 2008. Bivariate chi-square analysis was performed to examine
      differences in maternal report of WHO Maternal Health Interventions. Multivariate
      linear and logistic regression were performed to assess differences in antenatal
      care (ANC) scales and maternal care packages. RESULTS: Thousand and three hundred
      and sixty-seven rural women reported a live birth. Provider distribution was:
      doctor, 15.6%; midwife, 70%; community health officer (CHO), 9.1%; no provider,
      5.3%. Women from lower socio-demographic categories were more likely to report
      midwife or CHO. Report of CHO vs. no provider was positively associated with
      maternal services (P < 0.01). Report of doctor or midwife vs. CHO was
      significantly associated with maternal services (P < 0.01). CONCLUSION: There is
      a positive association between antenatal provider length of training and maternal
      specialization and report of maternal services. Community-based providers are
      associated with markedly increased report of maternal services compared with no
      provider. Structural factors appear to underlie some differences in service
      provision.

PMID- 23557102
TI  - Crestal approach for maxillary sinus augmentation in patients with <= 4 mm of
      residual alveolar bone.
AB  - PURPOSE: Less morbidity is the major advantage to a one-stage crestal approach to
      maxillary sinus elevation. However, the ability to ensure high primary implant
      stability in a severely atrophied ridge is of chief concern. The purpose of this
      study is to measure and compare the success rate of implants placed at the time
      of crestal approach sinus lift in patients with <= 4 mm of residual alveolar bone
      (RAB) and >4 mm of RAB. MATERIALS AND METHODS: In this three-site multicenter
      study, one hundred two patients, 53 males and 49 females, (23-89 years old; mean
      = 56.2) were evaluated. Three experienced surgeons (>15 years) performed the
      crestal approach sinus lift microsurgeries with simultaneous implant placement.
      At baseline and at the follow-up appointments, calibrated examiners measured
      radiographic interproximal bone level using ImageJ for Windows after calibration
      of the radiographs. References for the bone level measurements were the platform,
      first and second threads of the implants. Statistical analyses, using STATA
      version 12, stratified patients according to RAB height (group 1: RAB of <= 4 mm;
      n = 35 and group 2: RAB > 4 mm; n = 67), age, gender, and treatment center.
      RESULTS: The success rate was 100% for group 1 and 98.51% for group 2 at 6 to 100
      months postprosthetic loading (mean = 29.7 months). The peri-implant bone loss
      averaged 0.55 mm (interquartile range [IQR] = 0.5 [0-1]) in group 1 and 0.07 mm
      (IQR = 0 [0-0]) in group 2. There was no statistically significant difference
      between the two groups. Clinical outcomes were independent of age, gender, and
      treatment center. CONCLUSIONS: The RAB height did not increase crestal bone loss
      or reduce the success rate of the implants and associated prostheses. The crestal
      approach should be considered a viable technique for use in patients with
      residual bone height of <= 4 mm and merits further evaluation.

PMID- 23557103
TI  - Systematic review: Asian patients with chronic hepatitis C infection.
AB  - BACKGROUND: Chronic hepatitis C (CHC) infection is a risk factor for both the
      development of end-stage liver disease and hepatocellular carcinoma (HCC).
      Globally, approximately 170 million people are chronically infected with the
      hepatitis C virus (HCV), and the majority of these individuals come from the
      western Pacific and Southeast Asia regions (94.6 million persons combined). CHC
      is an understudied and underappreciated health problem in many Asian countries
      and in the US, where Asians represent one of the fastest growing groups of new
      Americans. AIM: To perform a systematic review of the current literature on the
      epidemiology, diagnosis and screening, clinical characteristics and response to
      anti-viral therapy of Asians with CHC. METHODS: Using a PubMed search of
      'hepatitis C' and 'Asia,' 341 original manuscripts published in peer-reviewed
      journals were identified, and 99 were selected based on their relevance. RESULTS:
      Many Asian CHC patients do not have easily identifiable risk factors and may be
      underdiagnosed. Rates of HCV infection in Asians on community screening in the US
      are unexpectedly high, and there is a high prevalence of HCV genotype 6 in
      Southeast Asia and Southern China. HCV-infected Asians tend to present at older
      age and may have higher risk of HCC; however, they respond better to anti-viral
      therapy than non-Asians across all HCV genotypes. CONCLUSIONS: Given the high HCV
      endemicity in Asia, lack of identifiable risk factors and favourable treatment
      response rates in Asians, we advocate the screening for HCV infection of all
      Asians who come from areas where HCV prevalence is >=2%.

PMID- 23557104
TI  - Staphylococcal scalded skin syndrome in neonates: an 8-year retrospective study
      in a single institution.
AB  - Staphylococcal scalded skin syndrome (SSSS) is a rare disorder in children.
      Complications may occur without timely treatment. Mortality in children with SSSS
      is approximately 4%. Other than a limited number of case reports, data on SSSS in
      neonates are limited. The objective of the current study was to investigate SSSS
      in neonates. A retrospective review of neonates with a diagnosis of SSSS from
      January 2004 to January 2012 was performed. Population distribution, historical
      features, physical examination findings including laboratory tests, antibiotic
      therapies, and outcomes were evaluated. Thirty-nine cases were included, 31
      (79.5%) in the last 4 years. The mean patient age was 17.4 +/- 7.7 days. Boys (25
      cases) were more commonly affected, and occurrence during summer and autumn
      months was more frequent. The face was the most common body part affected and the
      area most commonly initially affected. Fever, high white blood cell count, and
      high C-reactive protein levels were uncommon. Pneumonia was the most frequent
      complication (74.4%). The positive rate of Staphylococcus aureus isolation was
      low (23.5%). Drug susceptibility tests showed that amoxicillin with clavulanic
      acid and cephalosporins were effective in practice. The median length of
      hospitalization was 9.0 days. All of the 39 neonates were cured without scarring.
      This study established basic epidemiologic characteristics of a group of neonates
      diagnosed with SSSS. In the presence of a clinical suspicion of SSSS, even with
      apparently normal laboratory tests, immediate treatment with cephalosporins, beta
      lactamase-resistant semisynthetic penicillin, or both is advocated.

PMID- 23557106
TI  - Long-term effect of selective dorsal rhizotomy on gross motor function in
      ambulant children with spastic bilateral cerebral palsy, compared with reference
      centiles.
AB  - AIM: The aim of this study was to evaluate the long-term effect of selective
      dorsal rhizotomy (SDR) on the gross motor function of ambulant children with
      spastic bilateral cerebral palsy (CP), compared with reference centiles. METHOD:
      The study used a prospective cohort design and participants comprised 29 children
      classified using the Gross Motor Function Classification System (GMFCS) in level
      I (n=7), II (n=4), or III (n=18; 18 males, 11 females; median age at time of
      surgery 6 y 4 mo; range 2 y 10 mo-12 y 1 mo), who were examined 5 years and 10
      years after SDR. We used individual centiles based on Gross Motor Function
      Measure (GMFM-66) scores and age, corresponding to the GMFCS levels. Individual
      improvement or deterioration was defined as a change of more than 20 centiles.
      Side effects experienced and additional treatment received after SDR were also
      recorded. RESULTS: Five years after SDR, 10 out of 28 children showed
      improvement, and 10 years after SDR 6 out of 20 children had improved. Spinal
      side effects were noted in two children and hip subluxation in three. Additional
      treatments included subtalar arthrodesis (n=13), endorotational osteotomy of the
      tibia (n=5), and botulinum toxin treatment (n=13). INTERPRETATION: None of the
      children showed deterioration of gross motor function based on centile ranking.
      Five and 10 years after SDR, gross motor function in some children had improved
      more than would have been expected according to the reference centiles. This
      suggests, taking the limitations of this study into account, that the applied
      criteria for selection were adequate. However, the children still required
      additional treatment after SDR.

PMID- 23557107
TI  - Prevalence of common hemoglobin variants in an afro-descendent Ecuadorian
      population.
AB  - BACKGROUND: Hemoglobinopathies are among the most studied and frequent
      pathologies. These genetic disorders are considered a very important health care
      threat in many tropical countries. Ecuador is a tropical Latin-American country
      with an important presence of afro-descendants (7.2%). Afro-descendants are among
      the ethnic groups with higher frequency of hemoglobinopathies reported. Ambuqui
      is a region within the Imbabura province with an important presence of afro
      descendants (>50%). The present study analyzed the frequency of the most common
      hemoglobin variants in an asymptomatic afro-descendent population using capillary
      electrophoresis. FINDINGS: From 114 individuals, 25 (22%) reported a hemoglobin
      variant. All individuals that presented hemoglobin variants were heterozygotes
      (asymptomatic). Hemoglobin S (sickle cell trait) was the most frequent variant
      found (14%), followed by hemoglobin E (4.4%), Fetal (2.6%) and C (1%).
      CONCLUSION: Prevalence of hemoglobin S was consistent with populations from other
      countries, but it was lower than other Ecuadorian afro-descendent populations.
      Frequency of hemoglobin C was lower than other afro-descendent populations. This
      data suggests the possibility of gene flow from Native American individuals to
      the Ambuqui population there by lowering the frequency of their hemoglobin
      variants compared with other afro-descendant populations. Evaluating the
      frequency of hemoglobinopathies in Ecuadorian populations is essential. Despite
      the high frequency of these disorders, very few health care facilities implement
      hemoglobinopathies tests as a routine practice.

PMID- 23557108
TI  - Aquatic toxicity of cationic surfactants to Daphnia magna.
AB  - Quantitative structure-activity relationship (QSAR) modelling of aquatic toxicity
      for cationic surfactants has received limited attention despite the fact that
      surfactants of this type are generally more toxic than predicted by general
      narcosis or polar narcosis equations. Here we report measurement of log P for
      three types of aromatic quaternary ammonium halides at sub-micellar
      concentrations, refinement of earlier rules for log P calculation, and
      development of a hydrophobicity based QSAR, using both calculated and measured
      log P values, for the aquatic toxicity of quaternary ammonium halides to Daphnia
      magna. The QSAR for cationics has a substantially larger intercept than the log P
      based QSARs for nonionic and anionic surfactants. This is rationalised in terms
      of the head group interactions with membrane phospholipid in a two-dimensional
      partitioning model. The effect of the positive nitrogen on the log P
      contributions of methylene groups along alkyl chains varies, depending on the
      other groups bonded to the positive nitrogen. We propose a mechanistic
      explanation, but until these effects can be put on a more predictable
      quantitative basis it is recommended that, for quaternaries other than the three
      types discussed here, calculated log P values should not be relied on and
      experimental values should be determined, e.g. for prediction of toxicity by the
      QSAR equation reported here.

PMID- 23557109
TI  - Building research capital to facilitate research.
AB  - The National Institute for Health Research, Research Design Service (NIHR RDS)
      was set up to increase the number and proportion of high quality applications for
      funding for applied and patient focused health and social care research. Access
      to specialist expertise and collaboration between researchers and health
      practitioners at the proposal development stage is crucial for high quality
      applied health research. In this essay we develop the concept of 'research
      capital' to describe the wide range of resources and expertise required to
      develop fundable research projects. It highlights the key role the RDS plays
      supporting researchers to broker relationships to access the requisite 'research
      capital'.

PMID- 23557111
TI  - CUDASW++ 3.0: accelerating Smith-Waterman protein database search by coupling CPU
      and GPU SIMD instructions.
AB  - BACKGROUND: The maximal sensitivity for local alignments makes the Smith-Waterman
      algorithm a popular choice for protein sequence database search based on pairwise
      alignment. However, the algorithm is compute-intensive due to a quadratic time
      complexity. Corresponding runtimes are further compounded by the rapid growth of
      sequence databases. RESULTS: We present CUDASW++ 3.0, a fast Smith-Waterman
      protein database search algorithm, which couples CPU and GPU SIMD instructions
      and carries out concurrent CPU and GPU computations. For the CPU computation,
      this algorithm employs SSE-based vector execution units as accelerators. For the
      GPU computation, we have investigated for the first time a GPU SIMD
      parallelization, which employs CUDA PTX SIMD video instructions to gain more data
      parallelism beyond the SIMT execution model. Moreover, sequence alignment
      workloads are automatically distributed over CPUs and GPUs based on their
      respective compute capabilities. Evaluation on the Swiss-Prot database shows that
      CUDASW++ 3.0 gains a performance improvement over CUDASW++ 2.0 up to 2.9 and 3.2,
      with a maximum performance of 119.0 and 185.6 GCUPS, on a single-GPU GeForce GTX
      680 and a dual-GPU GeForce GTX 690 graphics card, respectively. In addition, our
      algorithm has demonstrated significant speedups over other top-performing tools:
      SWIPE and BLAST+. CONCLUSIONS: CUDASW++ 3.0 is written in CUDA C++ and PTX
      assembly languages, targeting GPUs based on the Kepler architecture. This
      algorithm obtains significant speedups over its predecessor: CUDASW++ 2.0, by
      benefiting from the use of CPU and GPU SIMD instructions as well as the
      concurrent execution on CPUs and GPUs. The source code and the simulated data are
      available at http://cudasw.sourceforge.net.

PMID- 23557110
TI  - Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor
      system and inflammatory biomarkers: a randomized open-label crossover study.
AB  - BACKGROUND: A marked reduction in serum levels of bioactive insulin-like growth
      factor-I (IGF-I) has been observed in fasting hemodialysis (HD) patients during a
      4-h HD session. The aim of the present study was to investigate the beneficial
      effect of hyperinsulinemia during HD on bioactive IGF-I and inflammatory
      biomarkers. METHODS: In a randomized cross-over study, 11 non-diabetic HD
      patients received a standardised HD session with either: 1) no treatment, 2)
      glucose infusion (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (10%
      glucose added 30 IU NovoRapid(r) per litre, 2.5 mL/kg/h). Each experiment
      consisted of three periods: pre-HD (-120 to 0 min), HD (0 to 240 min), and post
      HD (240 to 360 min). A meal was served at baseline (-120 min); infusions were
      administered from baseline to 240 min. The primary outcome was change in
      bioactive IGF-I during the experiment. Secondary outcomes were changes in high
      sensitivity C-reactive protein, interleukin-1beta, interleukin-6, and tumor
      necrosis factor alpha. Comparisons were performed using mixed-model analysis of
      variance for repeated measures. RESULTS: From baseline to the end of study, no
      significant differences were observed in the changes in either serum bioactive
      IGF-I or total IGF-I between study days. Overall, serum bioactive IGF-I levels
      rose above baseline at 120 to 300 min with a maximum increase of 20% at 120 min
      (95% confidence interval (CI), 9 to 31%; p < 0.001), whereas total IGF-I levels
      rose above baseline at 180 to 300 min with a maximum increase of 5% at 240 min
      (95% CI, 2 to 9%; p = 0.004). A significant difference was observed in the
      changes in serum IGF-binding protein-1 (IGFBP-1) between study days (p = 0.008),
      but differences were only significant in the post-HD period. From baseline to the
      end of HD, no significant difference was observed in the changes in serum IGFBP-1
      levels between study days, and in this time period overall serum IGFBP-1 levels
      were below baseline at all time points with a maximum decrease of 51% at 180 min
      (95% CI, 45 to 57%; p < 0.001). None of the investigated inflammatory biomarkers
      showed any differences in the changes over time between study days. CONCLUSIONS:
      Postprandial insulin secretion stimulated the IGF-system during HD with no
      further effect of adding glucose or glucose-insulin infusion. Hyperinsulinemia
      during HD had no effect on biomarkers of inflammation. TRIAL REGISTRATION:
      ClinicalTrials.gov registry: NCT01209403.

PMID- 23557112
TI  - Enhancing frontline clinical leadership in an acute hospital trust.
AB  - AIMS AND OBJECTIVES: To report on a leadership programme for ward managers in one
      National Health Service Trust that aimed to enhance their contribution to the
      delivery of the organisation's key objectives to support excellent patient
      experience. BACKGROUND: Effective ward leadership has been recognised as vital to
      the quality of care, resource management and interprofessional working. However,
      there is evidence that, at present, front-line nurse leaders are ill equipped to
      lead effectively and lack confidence in their ability to do so. DESIGN: The
      project aimed to provide a tailored programme for ward managers to develop their
      portfolio of skills to perform this pivotal role. The course contained two key
      elements: an integrated teaching programme to enhance leadership knowledge and
      skills and action learning to facilitate application to individual's own
      leadership practice. Both were underpinned by a change project where each
      individual identified, undertook and evaluated an innovation in practice.
      METHODS: Twenty-two ward managers completed the leadership programme.
      Participants completed semi-structured questionnaires after each taught module.
      Action learning was evaluated through a combined structured and semi-structured
      questionnaire. RESULTS: All participants evaluated the programme as increasing
      their repertoire of leadership skills. Following completion of the programme,
      ward managers continue to work together as an evolving community of practice.
      CONCLUSION: Ward managers' development is enhanced by a programme integrating
      theory, action learning and completion of a ward-based project. RELEVANCE TO
      CLINICAL PRACTICE: Ward managers cannot be effectively developed in isolation.
      Leadership development is best supported where the organisation is also committed
      to developing. A leadership development programme that incorporates knowledge
      from within the organisation with external expertise can be an effective method
      to enhance front-line clinical leadership.

PMID- 23557113
TI  - Recent developments in texaphyrin chemistry and drug discovery.
AB  - Texaphyrins are pentaaza expanded porphyrins with the ability to form stable
      complexes with a variety of metal cations, particularly those of the lanthanide
      series. In biological milieus, texaphyrins act as redox mediators and mediate the
      production of reactive oxygen species (ROS). In this review, newer studies
      involving texaphyrin complexes targeting several different applications in
      anticancer therapy are described. In particular, the preparation of bismuth and
      lead texaphyrin complexes as potential alpha-core emitters for radiotherapy is
      detailed, as are gadolinium texaphyrin functionalized magnetic nanoparticles with
      features that make them of interest as dual-mode magnetic resonance imaging
      contrast agents and as constructs with anticancer activity mediated through ROS
      induced sensitization and concurrent hyperthermia. Also discussed are gadolinium
      texaphyrin complexes as possible carrier systems for the targeted delivery of
      platinum payloads. 

PMID- 23557114
TI  - Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus
      erythematosus: diagnostic performance and clinical profile.
AB  - BACKGROUND: This study was devised to assess the performance of anti-ribosomal P
      (anti-Rib-P) antibodies in the diagnosis of systemic lupus erythematosus (SLE)
      and the association of these antibodies with the clinical features of SLE.
      METHODS: We used a fluorescence enzyme immunoassay to determine anti-Rib-P levels
      in an SLE group, a rheumatic disease control (RDC) group (rheumatoid arthritis
      (RA), ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic
      arthritis), and a healthy control (HC) group. We also determined anti-Smith
      antigen (anti-Sm) and anti-double-stranded DNA (anti-dsDNA) antibody levels.
      Receiver operating characteristic (ROC) curves were constructed and the best cut
      off points for positivity were determined. Using regression analysis, the
      relationship between clinical variables and autoantibody levels was analyzed.
      RESULTS: In total, 127 patients with SLE, 256 controls with other rheumatic
      diseases, and 100 HCs were studied. Anti-Rib-P autoantibodies were positive in 18
      (14.2%) of the patients with SLE (mean concentration of 30.6 +/- 46.9 U/ml) and
      in 2 patients with RA (0.8% of the RDC group). In addition, 12 patients with SLE
      (9.4%) were positive for anti-Sm (31.1 +/- 40.8 U/ml) and 63 (49.6%) were
      positive for anti-dsDNA autoantibodies (88.4 +/- 88.5 U/ml). When we assessed the
      18 patients with SLE who had tested positive for anti-Rib-P, we found that 4 of
      these were positive for anti-Rib-P only, whereas 12 were positive for anti-Rib-P
      plus anti-dsDNA, and 2 were positive for all three antibodies. There were no
      samples positive for anti-Rib-P plus anti-Sm. The specificity, sensitivity,
      positive likelihood ratio, and negative likelihood ratio of anti-Rib-P for SLE
      diagnosis were 99.4%, 14.2%, 23.7%, and 0.86%, respectively.Caucasian ethnicity
      was associated with lower anti-Rib-P antibody levels. No relation was found
      between anti-Rib-P levels and neuropsychiatric or other clinical features.
      CONCLUSIONS: Anti-Rib-P autoantibodies have high specificity for SLE, and
      measurement of these might improve the accuracy of SLE diagnosis. In this study,
      we found that Caucasian ethnicity was associated with lower anti-Rib-P antibody
      levels.

PMID- 23557116
TI  - Latino parents' plans to communicate about sexuality with their children.
AB  - This study investigated 86 Latino parents' intentions to communicate about
      sexuality issues with their children. They reported on their history of sexuality
      education, when they would first discuss sexuality-related topics, and their
      perceived effectiveness of each topic. Compared with a sample of Caucasian
      parents, Latino parents intended to discuss sexual abuse/molestation at an
      earlier age, but planned to discuss human reproduction, intercourse, and AIDS at
      significantly later ages. Suggestions for assisting Latino parents with
      communications regarding sexuality topics are provided. 

PMID- 23557115
TI  - The role of the combination of bone and fall related risk factors on short-term
      subsequent fracture risk and mortality.
AB  - BACKGROUND: We analysed whether a combination of bone- and fall-related risk
      factors (RFs) in addition to a recent non-vertebral fracture (NVF) contributed to
      subsequent NVF risk and mortality during 2-years in patients who were offered
      fall and fracture prevention according to Dutch fracture- and fall-prevention
      guidelines. METHODS: 834 consecutive patients aged >=50 years with a recent NVF
      who were included. We compared subgroups of patients according to the presence of
      bone RFs and/or fall RFs (group 1: only bone RFs; group 2: combination of bone
      and fall RFs; group 3: only fall RFs; group 4: no additional RFs). Univariable
      and multivariable Cox regression analyses were performed adjusted for age, sex
      and baseline fracture location (major or minor). RESULTS: 57 (6.8%) had a
      subsequent NVF and 29 (3.5%) died within 2-years. Univariable Cox regression
      analysis showed that patients with the combination of bone and fall RFs had a 99%
      higher risk in subsequent fracture risk compared to all others (Hazard Ratio (HR)
      1.99; 95% Confidence Interval (CI) 1.18-3.36) Multivariable analyses this was
      borderline not significant (HR 1.70; 95% CI: 0.99-2.93). No significant
      differences in mortality were found between the groups. CONCLUSION: Evaluation of
      fall RFs contributes to identifying patients with bone RFs at highest immediate
      risk of subsequent NVF in spite of guideline-based treatment. It should be
      further studied whether earlier and immediate prevention following a NVF can
      decrease fracture risk in patients with a combination of bone and fall RFs.

PMID- 23557117
TI  - Efficient protection and transfection of small interfering RNA by cationic shell
      crosslinked knedel-like nanoparticles.
AB  - Despite the great potential of small interfering RNA (siRNA) as a therapeutic
      agent, progress in this area has been hampered by a lack of efficient
      biocompatible transfection agents. Recently, cationic shell-crosslinked knedel
      like nanoparticles (cSCKs) were found to possess lower cytotoxicity and better
      transfection ability for phosphorothioate ODNs and plasmid DNA than the commonly
      used cationic lipid-based agent Lipofectamine. To determine the usefulness of
      cSCKs for siRNA transfection, a small library of cSCKs with varying percentage of
      primary and tertiary amines was assessed for its ability to bind to siRNA,
      inhibit siRNA degradation in human serum, and to transfect HeLa and mouse
      macrophage cell lines. The silencing efficiency in HeLa cells was greatest with
      the cSCK with 100% primary amines (pa100) as determined by their viability
      following transfection with cytotoxic and non-cytotoxic siRNAs. cSCK-pa100 showed
      greater silencing efficiency than Lipofectamine 2000 in the HeLa cells, as well
      in 293T and human bronchial epithelial (HEK) cells, but was comparable in human
      bronchial epithelial (BEAS-2B) cells and human mammary epithelial (MCF10a) cells.
      cSCK-pa100 also showed greater silencing of iNOS expression than Lipofectamine
      2000 in a mouse macrophage cell line, and provided greater protection from serum
      degradation, demonstrating its potential usefulness as an siRNA transfection
      agent. The siRNA silencing of iNOS at lower concentrations of siRNA could be
      enhanced by complexation with the fusogenic GALA peptide, which was shown to
      enhance endosomal escape following uptake.

PMID- 23557118
TI  - Designing DNA barcodes orthogonal in melting temperature by simulated annealing
      optimization.
AB  - Molecular barcode arrays are widely employed in the analysis of large strain
      libraries, whereby probes linked to unique oligonucleotides ("antitags") are used
      to detect selected DNA targets ("tags") by highly specific hybridization. One of
      the major problems for such screen designs is thus insuring a high degree of
      probe-target specificity and a low level of nonspecific binding (in sum,
      "orthogonality") across the entire tag population ("collection"). Several
      approaches have been previously proposed for designing orthogonal DNA tags by
      among others-focusing on their individual or pair-wise structures, such as Smith
      Waterman sequence similarity, the widely used nearest neighbor method, and full
      thermodynamic estimates of sequences. However, these methods generally involve
      imposing various heuristic constraints ("design rules") on possible tag/antitag
      (TaT) sequences in order to achieve probe-target specificity across the
      collection. The resulting lack of freedom in considering all putative sequences
      can lead to potentially suboptimal designs and to the ensuing reduction in the
      degree of orthogonality within the constructed TaT collections. Here, we
      demonstrate that a randomized-search algorithm based on simulated annealing
      optimization can be used in order to substantially free the design process from
      the limitations of sequence constraints-allowing for the elucidation of
      potentially more optimal DNA tag collections. The designed sets of DNA
      oligonucleotides are optimized for the highest degree of orthogonality as
      quantified by melting temperature Tm-an experimentally relevant system property,
      which could also be used as a theoretically meaningful thermodynamic metric for
      optimizing TaT binding specificity. That is, this work describes an approach to
      constructing tag/antitag libraries, which offer the greatest melting temperature
      separation between specific probe-target duplexes and other nonspecific
      structures. The proposed method finds, with high probability, the global solution
      that maximizes the difference in Tm between the specific and nonspecific tag
      antitag hybridizations across a collection of given size for TaTs of specified
      length. An application of this approach is demonstrated using 2 different DNA
      probe sets.

PMID- 23557119
TI  - Assessing fidelity of delivery of smoking cessation behavioural support in
      practice.
AB  - BACKGROUND: Effectiveness of evidence-based behaviour change interventions is
      likely to be undermined by failure to deliver interventions as planned.
      Behavioural support for smoking cessation can be a highly cost-effective, life
      saving intervention. However, in practice, outcomes are highly variable. Part of
      this may be due to variability in fidelity of intervention implementation. To
      date, there have been no published studies on this. The present study aimed to:
      evaluate a method for assessing fidelity of behavioural support; assess fidelity
      of delivery in two English Stop-Smoking Services; and compare the extent of
      fidelity according to session types, duration, individual practitioners, and
      component behaviour change techniques (BCTs). METHODS: Treatment manuals and
      transcripts of 34 audio-recorded behavioural support sessions were obtained from
      two Stop-Smoking Services and coded into component BCTs using a taxonomy of 43
      BCTs. Inter-rater reliability was assessed using percentage agreement. Fidelity
      was assessed by examining the proportion of BCTs specified in the manuals that
      were delivered in individual sessions. This was assessed by session type (i.e.,
      pre-quit, quit, post-quit), duration, individual practitioner, and BCT. RESULTS:
      Inter-coder reliability was high (87.1%). On average, 66% of manual-specified
      BCTs were delivered per session (SD 15.3, range: 35% to 90%). In Service 1,
      average fidelity was highest for post-quit sessions (69%) and lowest for pre-quit
      (58%). In Service 2, fidelity was highest for quit-day (81%) and lowest for post
      quit sessions (56%). Session duration was not significantly correlated with
      fidelity. Individual practitioner fidelity ranged from 55% to 78%. Individual
      manual-specified BCTs were delivered on average 63% of the time (SD 28.5, range:
      0 to 100%). CONCLUSIONS: The extent to which smoking cessation behavioural
      support is delivered as specified in treatment manuals can be reliably assessed
      using transcripts of audiotaped sessions. This allows the investigation of the
      implementation of evidence-based practice in relation to smoking cessation, a
      first step in designing interventions to improve it. There are grounds for
      believing that fidelity in the English Stop-Smoking Services may be low and that
      routine monitoring is warranted.

PMID- 23557120
TI  - An interview with Michael Carmont, section editor for the surgery, traumatology,
      and rehabilitation section on sports traumatology research: acute, overuse and
      chronic problems, early return to play and long-term outcomes.

PMID- 23557121
TI  - Eczematide-like purpura presenting as Ofuji papuloerythroderma: a case that
      confirms this as a pattern.

PMID- 23557122
TI  - TPGS emulsified zein nanoparticles enhanced oral bioavailability of daidzin: in
      vitro characteristics and in vivo performance.
AB  - A novel drug delivery system, TPGS 1000 (TPGS) emulsified zein nanoparticles
      (TZN), were designed with an objective to improve the oral bioavailability of
      daidzin, an isoflavone glycoside with estrogenic activities. Zein nanoparticles
      (ZN) and TZN were fabricated using an antisolvent method. They were found to be
      spherical in shape with a mean size around 200 nm and a low polydispersity. Their
      zeta potentials were about +25 mV at pH 5.5 and -23 mV at pH 7.4. Adding TPGS as
      an emulsifier increased the encapsulation efficiency of daidzin in ZN from 53% to
      63%. Daidzin loaded TZN had a slower daidzin release compared with daidzin loaded
      ZN in both simulated digestive fluids and a pH 7.4 buffer. Confocal laser
      scanning microscopy suggested that the cellular uptake of coumarin-6 labeled TZN
      in human intestinal epithelial Caco-2 cells were significantly higher than
      fluorescent ZN. Cellular uptake and transport studies revealed that daidzin in
      TZN were taken up more efficiently into Caco-2 cells and transported more quickly
      through Caco-2 monolayer than daidzin solution. A pharmacokinetic study
      demonstrated that the Cmax of daidzein in mice after oral administration of
      daidzin loaded TZN was 5.66 +/- 0.16 MUM, which was improved by 2.64-fold
      compared with that of daidzin solution (2.14 +/- 0.04 MUM). Moreover, the areas
      under the curve (AUC0-12 h) for daidzin loaded in TZN were enhanced by 2.4-fold
      compared with that of daidzin solution. These results suggested that TZN could be
      an effective strategy to improve the oral bioavailability of isoflavone
      glycosides like daidzin.

PMID- 23557123
TI  - Use of opioids for pain relief while driving: when the patient meets the police.

PMID- 23557125
TI  - An improved tool for household faeces management in rural Bangladeshi
      communities.
AB  - OBJECTIVE: To explore child defecation and faeces management practices in rural
      Bangladesh with the aim to redesign and pilot a tool to facilitate removal and
      disposal of faeces. METHODS: We conducted six group discussions, six short
      interviews and three observations of practices and designed the new tool. We
      piloted the new tool and elicited feedback through two in-depth interviews and
      two observations. RESULTS: Until three years of age, a child commonly defecates
      in the courtyard and occasionally inside the house. A heavy digging hoe was
      commonly used to remove child faeces. Mothers preferred a redesigned 'mini-hoe'
      and found it easier to use for removal and disposal of liquid faeces.
      CONCLUSIONS: Promoting modified local tools may contribute to improving
      environmental sanitation and health.

PMID- 23557126
TI  - Deregulated systemic IL-10/IL-12 balance in advanced and poor prognosis
      paediatric soft tissue sarcomas.
AB  - CONTEXT: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer
      growth and Th1/Th2 immune responses towards cancer are unclear. OBJECTIVE: To
      establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft
      tissue sarcomas (STS). MATERIALS AND METHODS: ELISA determinations of cytokines
      were performed as pre-treatment in 59 children with STS and 30 healthy controls.
      RESULTS: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced
      disease, poor response to chemotherapy and poor outcome. IL-10 >= 9.5 pg/ml, IL
      12 <= 65 pg/ml and lymph nodes involvement independently predicted poor overall
      survival (OS) in multivariate Cox analysis. CONCLUSION: Serum IL-10/IL-12 balance
      determination may facilitate to assess risk groups and prognosis in childhood
      STS.

PMID- 23557127
TI  - Interleukin receptor family member ST2 concentrations in patients following heart
      transplantation.
AB  - OBJECTIVE: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft
      vasculopathy and mortality after orthotopic heart transplantation (OHT). METHODS:
      sST2 concentrations were measured in 241 patients following OHT. RESULTS:
      Elevated sST2 was associated with cellular rejection (CR) >= 1R, with highest
      rates of CR in the 4th sST2 quartile (p = 0.003). No significant association
      between sST2 and antibody-mediated rejection or allograft vasculopathy was found.
      sST2 >= 30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01;
      95% CI 1.15-3.51; p = 0.01). CONCLUSION: Concentrations of sST2 are associated
      with the presence of CR and predict long-term mortality following OHT.

PMID- 23557129
TI  - A predictive microarray-based biomarker for early detection of Alzheimer's
      disease intended for clinical diagnostic application.
AB  - OBJECTIVE: Microarray-based signatures for clinical application are often plagued
      by processing variability or batch effects that compromise the robustness of the
      test performance. METHODS: A splice variant array-based signature for early
      detection of Alzheimer's disease (AD) was developed using 315 AD or normal
      subjects processed in three disparate microarray batches. RESULTS: A modified top
      scoring pair classifier using the signature, is robust to batch effects and
      outperforms other common classifiers, with sensitivity and specificity of 88.3%
      (95% CI:81.2%, 93.4%) and 88.9% (95% CI:65.3%, 98.6%), respectively, on an
      independent cohort. CONCLUSIONS: This splice-variant array-based signature shows
      promise for clinical diagnostic use in AD.

PMID- 23557130
TI  - S100A12 levels in synovial fluid may reflect clinical severity in patients with
      primary knee osteoarthritis.
AB  - This study aims to detect S100A12 in serum and synovial fluid (SF) of knee
      osteoarthritis (OA) patients and to investigate their correlation with clinical
      severity of the disease. This study enrolled 198 OA patients and 84 healthy
      controls. The radiological/symptomatic severity of the disease was assessed by
      the Kellgren-Lawrence (KL) grading system/Western Ontario McMaster University
      Osteoarthritis (WOMAC) scores. We demonstrated that S100A12 levels in SF but not
      serum were independently associated with KL grades and WOMAC scores. These
      results suggested that the S100A12 in SF might be a potential biomarker for
      predicting the development and progression of knee OA.

PMID- 23557131
TI  - Eosinophil-derived neurotoxin levels at 3 months post-respiratory syncytial virus
      bronchiolitis are a predictive biomarker of recurrent wheezing.
AB  - OBJECTIVE: To determine whether eosinophil-derived neurotoxin (EDN) is a
      predictive marker of recurrent wheezing episodes in post-respiratory syncytial
      virus (RSV) bronchiolitis. METHODS: EDN levels and recurrent wheezing episodes
      were serially measured in 200 infants hospitalized with RSV bronchiolitis.
      RESULTS: Serum EDN levels at 3 months correlated significantly with total
      wheezing episodes at 12 months in the RSV-PLC (n  = 71; r = 0.720, p < 0.0001)
      and RSV-MONT groups (n = 79; r = 0.531, p < 0.001). Positive predictive value of
      3-mo EDN level for total wheezing episodes was 57%; negative predictive value,
      76%; sensitivity, 72%; specificity, 62%. CONCLUSION: EDN levels have predictive
      value for the development of recurrent wheezing post-RSV bronchiolitis.

PMID- 23557132
TI  - Detection of mixing dynamics during pumping of a flooded coal mine.
AB  - In complex hydrogeological environments the effective management of groundwater
      quality problems by pump-and-treat operations can be most confidently achieved if
      the mixing dynamics induced within the aquifer by pumping are well understood.
      The utility of isotopic environmental tracers (C-, H-, O-, S-stable isotopic
      analyses and age indicators-(14) C, (3) H) for this purpose is illustrated by the
      analysis of a pumping test in an abstraction borehole drilled into flooded,
      abandoned coal mineworkings at Deerplay (Lancashire, UK). Interpretation of the
      isotope data was undertaken conjunctively with that of major ion hydrochemistry,
      and interpreted in the context of the particular hydraulic setting of flooded
      mineworkings to identify the sources and mixing of water qualities in the
      groundwater system. Initial pumping showed breakdown of initial water quality
      stratification in the borehole, and gave evidence for distinctive isotopic
      signatures (delta(34) S(SO4) ? -1.60/00, delta(18) O(SO4 ) ? +150/00) associated
      with primary oxidation of pyrite in the zone of water table fluctuation-the first
      time this phenomenon has been successfully characterized by these isotopes in a
      flooded mine system. The overall aim of the test pumping-to replace an
      uncontrolled outflow from a mine entrance in an inconvenient location with a
      pumped discharge on a site where treatment could be provided-was swiftly
      achieved. Environmental tracing data illustrated the benefits of pumping as
      little as possible to attain this aim, as higher rates of pumping induced in
      mixing of poorer quality waters from more distant old workings, and/or renewed
      pyrite oxidation in the shallow subsurface. 

PMID- 23557128
TI  - Adhesion molecules, endothelin-1 and lung function in seven population-based
      cohorts.
AB  - CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary
      disease (COPD); whether endothelial dysfunction causes COPD is unknown.
      OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using
      instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM
      1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS:
      ICAM-1 and P-selectin were inversely associated with FEV1 among European
      Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker,
      p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008).
      Genetically-estimated ICAM-1 and P-selectin were not significantly associated
      with FEV1. The instrumental variable for endothelin-1 was non-informative.
      CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely
      associated with FEV1, associations for ICAM-1 and P-selectin do not appear
      causal.

PMID- 23557133
TI  - Fibroblast growth factor-1 is a mesenchymal stromal cell-secreted factor
      stimulating proliferation of osteoarthritic chondrocytes in co-culture.
AB  - Previously, we showed that mesenchymal stromal cells (MSCs) in co-culture with
      primary chondrocytes secrete soluble factors that increase chondrocyte
      proliferation. The objective of this study is to identify these factors. Human
      primary chondrocytes (hPCs) isolated from late-stage osteoarthritis patients were
      co-cultured with human bone marrow-derived MSCs (hMSCs) in pellets. Genome-wide
      mRNA expression analysis and quantitative polymerase chain reactions (qPCR) were
      used to identify soluble factors that were specifically induced in co-cultures.
      Immunofluorescent staining combined with cell tracking and enzyme-linked
      immunosorbent assay (ELISA) were performed to validate up-regulation at the
      protein level and to identify the cellular origin of the increased proteins.
      Chemical blockers and neutralizing antibodies were used to elucidate the role of
      the identified candidate genes in co-cultures. A number of candidate factors were
      differentially regulated in co-cultures at the mRNA level. Of these, fibroblast
      growth factor-1 (FGF-1) mRNA and protein expression were markedly increased in co
      cultures predominantly due to up-regulated expression in MSCs. Blocking of FGF
      signaling in co-culture pellets by specific FGF receptor inhibitors or FGF-1
      neutralizing antibodies completely blocked hPCs proliferation. We demonstrate
      that MSCs increase FGF-1 secretion on co-culture with hPCs, which, in turn, is
      responsible for increased hPCs proliferation in pellet co-cultures. 

PMID- 23557134
TI  - Maternity care providers' perceptions of women's autonomy and the law.
AB  - BACKGROUND: Like all health care consumers, pregnant women have the right to make
      autonomous decisions about their medical care. However, this right has created
      confusion for a number of maternity care stakeholders, particularly in situations
      when a woman's decision may lead to increased risk of harm to the fetus. Little
      is known about care providers' perceptions of this situation, or of their legal
      accountability for outcomes experienced in pregnancy and birth. This paper
      examined maternity care providers' attitudes and beliefs towards women's right to
      make autonomous decisions during pregnancy and birth, and the legal
      responsibility of professionals for maternal and fetal outcomes. METHODS:
      Attitudes and beliefs around women's autonomy and health professionals' legal
      accountability were measured in a sample of 336 midwives and doctors from both
      public and private health sectors in Queensland, Australia, using a questionnaire
      available online and in paper format. Student's t-test was used to compare
      midwives' and doctors' responses. RESULTS: Both maternity care professionals
      demonstrated a poor understanding of their own legal accountability, and the
      rights of the woman and her fetus. Midwives and doctors believed the final
      decision should rest with the woman; however, each also believed that the needs
      of the woman may be overridden for the safety of the fetus. Doctors believed
      themselves to be ultimately legally accountable for outcomes experienced in
      pregnancy and birth, despite the legal position that all health care
      professionals are responsible only for adverse outcomes caused by their own
      negligent actions. Interprofessional differences were evident, with midwives and
      doctors significantly differing in their responses on five of the six items.
      CONCLUSIONS: Maternity care professionals inconsistently supported women's right
      to autonomous decision making during pregnancy and birth. This finding is further
      complicated by care providers' poor understanding of legal accountability for
      outcomes experienced in pregnancy and birth. The findings of this study support
      the need for guidelines on decision making in pregnancy and birth for maternity
      care professionals, and for recognition of interprofessional differences in
      beliefs around the rights of the woman, her fetus and health professionals in
      order to facilitate collaborative practice.

PMID- 23557135
TI  - Successful treatment of congenital erythropoietic porphyria using matched
      unrelated hematopoietic stem cell transplantation.
AB  - Congenital erythropoietic porphyria (CEP), or Gunther's disease, is an inborn
      error of metabolism produced by a deficiency of uroporphyrinogen III synthase
      (UROS), the fourth enzyme of the heme biosynthesis pathway. This enzymatic defect
      induces the accumulation of isomer I porphyrins in erythrocytes, skin, and
      tissues, producing various clinical manifestations. Severe cases are
      characterized by extreme photosensitivity, causing scarring and mutilations, and
      by hemolytic anemia, reducing life expectancy. CEP is caused by mutations in the
      UROS gene, and one of the most severe forms of the disease is associated with a
      cysteine to arginine substitution at residue 73 of the protein (C73R). CEP has
      been successfully treated only by the transplantation of hematopoietic
      precursors. We report the case of a male infant with severe postdelivery symptoms
      diagnosed with CEP and found to be homozygous for the C73R mutation. He underwent
      successful allogeneic bone marrow transplantation from a matched unrelated donor
      at 7 months of age. The hemolytic anemia was corrected and the porphyrin
      overproduction was significantly reduced. The patient remained asymptomatic after
      1 year. This new case confirms that patients with severe CEP can benefit from
      early postnatal hematopoietic stem cell transplantation.

PMID- 23557136
TI  - Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential
      xenoestrogens: a QSAR comparative analysis*.
AB  - Alternative methods, including quantitative structure-activity relationships
      (QSAR), are being used increasingly when appropriate data for toxicity evaluation
      of chemicals are not available. Approximately 40 mono-hydroxylated
      polychlorinated biphenyls (OH-PCBs) have been identified in humans. They
      represent a health and environmental concern because some of them have been shown
      to have agonist or antagonist interactions with human hormone receptors. This
      could lead to modulation of steroid hormone receptor pathways and endocrine
      system disruption. We performed QSAR analyses using available estrogenic activity
      (human estrogen receptor ER alpha) data for 71 OH-PCBs. The modelling was
      performed using multiple molecular descriptors including electronic, molecular,
      constitutional, topological, and geometrical endpoints. Multiple linear
      regressions and recursive partitioning were used to best fit descriptors. The
      results show that the position of the hydroxyl substitution, polarizability, and
      meta adjacent un-substituted carbon pairs at the phenolic ring contribute towards
      greater estrogenic activity for these chemicals. These comparative QSAR models
      may be used for predictive toxicity, and identification of health consequences of
      PCB metabolites that lack empirical data. Such information will help prioritize
      such molecules for additional testing, guide future basic laboratory research
      studies, and help the health/risk assessment community understand the complex
      nature of chemical mixtures.

PMID- 23557137
TI  - Electrochemical biosensor applications of polysaccharides chitin and chitosan.

PMID- 23557138
TI  - Reactive oxygen species responsive nanoprodrug to treat intracranial
      glioblastoma.
AB  - Chemotherapy for intracranial gliomas is hampered by limited delivery of
      therapeutic agents through the blood brain barrier (BBB). An optimal therapeutic
      agent for brain tumors would selectively cross the BBB, accumulates in the tumor
      tissue and be activated from an innocuous prodrug within the tumor. Here we show
      brain tumor-targeted delivery and therapeutic efficacy of a nanometer-sized
      prodrug (nanoprodrug) of camptothecin (CPT) to treat experimental glioblastoma
      multiforme (GBM). The CPT nanoprodrug was prepared using spontaneous
      nanoemulsification of a biodegradable, antioxidant CPT prodrug and alpha
      tocopherol. The oxidized nanoprodrug was activated more efficiently than
      nonoxidized nanoprodrug, suggesting enhanced therapeutic efficacy in the
      oxidative tumor microenvironment. The in vitro imaging of U-87 MG glioma cells
      revealed an efficient intracellular uptake of the nanoprodrug via direct cell
      membrane penetration rather than via endocytosis. The in vivo study in mice
      demonstrated that the CPT nanoprodrug passed through the BBB and specifically
      accumulated in brain tumor tissue, but not in healthy brain tissue and other
      organs. The accumulation preferably occurred at the periphery of the tumor where
      cancer cells are most actively proliferating, suggesting optimal therapeutic
      efficacy of the nanoprodrug. The nanoprodrug was effective in treating
      subcutaneous and intracranial tumors. The nanoprodrug inhibited subcutaneous
      tumor growth more than 80% compared with control. The median survival time of
      mice implanted with an intracranial tumor increased from 40.5 days for control to
      72.5 days for CPT nanoprodrug. This nanoprodrug approach is a versatile method
      for developing therapeutic nanoparticles enabling tumor-specific targeting and
      treatment. The nontoxic, tumor-specific targeting properties of the nanoprodrug
      system make it a safe, low cost, and versatile nanocarrier for pharmaceuticals,
      imaging agents, and diagnostic agents.

PMID- 23557139
TI  - Non-invasive tests for fibrosis and liver stiffness predict 5-year survival of
      patients chronically infected with hepatitis B virus.
AB  - BACKGROUND: Liver stiffness and non-invasive tests predict overall survival in
      chronic hepatitis C. However, in patients chronically infected with hepatitis B
      virus (HBV), only the association between liver stiffness and the risk of
      hepatocellular carcinoma has been published. AIM: To evaluate the 5-year
      prognostic value of liver stiffness, non-invasive tests of liver fibrosis, and
      liver biopsy, to predict overall survival in chronic hepatitis B. METHODS: In a
      consecutive cohort, we prospectively assessed fibrosis, with liver stiffness,
      FibroTest, APRI, FIB-4 and liver biopsy (if indicated). We examined death and
      liver transplantation during a 5-year follow-up, and factors associated with
      overall survival. RESULTS: A total of 600 patients (men 64%, mean age 42 years,
      inactive carriers 36%) with chronic hepatitis B were included. At 5 years, 25
      patients were dead (13 liver-related deaths) and four patients had liver
      transplantation. Overall survival was 94.1% and survival without liver-related
      death 96.3%. No liver-related death was observed in inactive carriers. Survival
      was significantly decreased in patients diagnosed with severe fibrosis, whatever
      the non-invasive method used (P < 0.0001), or liver biopsy (P = 0.02). Patients'
      prognosis decreased as liver stiffness and FibroTest increased. In multivariate
      analysis, FibroTest and liver stiffness had the highest hazard ratio with
      survival. The association persisted after adjustment on age, necro-inflammatory
      histological activity presumed by ActiTest and treatment. CONCLUSIONS: Liver
      stiffness measurement or FibroTest can predict survival in chronic HBV infection.
      Thus, these tools may help physicians to early assess prognosis and discuss
      specific treatments, such as liver transplantation.

PMID- 23557140
TI  - The PinkThing for analysing ChIP profiling data in their genomic context.
AB  - BACKGROUND: Current epigenetic research makes frequent use of whole-genome ChIP
      profiling for determining the in vivo binding of proteins, e.g. transcription
      factors and histones, to DNA. Two important and recurrent questions for these
      large scale analyses are: 1) What is the genomic distribution of a set of binding
      sites? and 2) Does this genomic distribution differ significantly from another
      set of sites? FINDINGS: We exemplify the functionality of the PinkThing by
      analysing a ChIP profiling dataset of cohesin binding sites. We show the subset
      of cohesin sites with no CTCF binding have a characteristic genomic distribution
      different from the set of all cohesin sites. CONCLUSIONS: The PinkThing is a web
      application for fast and easy analysis of the context of genomic loci, such as
      peaks from ChIP profiling experiments. The output of the PinkThing analysis
      includes: categorisation of position relative to genes (intronic, exonic, 5'
      near, 3' near 5' far, 3' far and distant), distance to the closest annotated 3'
      and 5' end of genes, direction of transcription of the nearest gene, and the
      option to include other genomic elements like ESTs and CpG islands. The PinkThing
      enables easy statistical comparison between experiments, i.e. experimental versus
      background sets, reporting over- and underrepresentation as well as p-values for
      all comparisons. Access and use of the PinkThing is free and open (without
      registration) to all users via the website: http://pinkthing.cmbi.ru.nl

PMID- 23557141
TI  - Are multidisciplinary teams in secondary care cost-effective? A systematic review
      of the literature.
AB  - OBJECTIVE: To investigate the cost effectiveness of management of patients within
      the context of a multidisciplinary team (MDT) meeting in cancer and non-cancer
      teams in secondary care. DESIGN: Systematic review. DATA SOURCES: EMBASE,
      MEDLINE, NHS EED, CINAHL, EconLit, Cochrane Library, and NHS HMIC. ELIGIBILITY
      CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs), cohort, case
      control, before and after and cross-sectional study designs including an economic
      evaluation of management decisions made in any disease in secondary care within
      the context of an MDT meeting. DATA EXTRACTION: Two independent reviewers
      extracted data and assessed methodological quality using the Consensus on Health
      Economic Criteria (CHEC-list). MDTs were defined by evidence of two
      characteristics: decision making requiring a minimum of two disciplines; and
      regular meetings to discuss diagnosis, treatment and/or patient management,
      occurring at a physical location or by teleconferencing. Studies that reported on
      the costs of administering, preparing for, and attending MDT meetings and/or the
      subsequent direct medical costs of care, non-medical costs, or indirect costs,
      and any health outcomes that were relevant to the disease being investigated were
      included and classified as cancer or non-cancer MDTs. RESULTS: Fifteen studies
      (11 RCTs in non-cancer care, 2 cohort studies in cancer and non-cancer care, and
      2 before and after studies in cancer and non cancer care) were identified, all
      with a high risk of bias. Twelve papers reported the frequency of meetings which
      varied from daily to three monthly and all reported the number of disciplines
      included (mean 5, range 2 to 9). The results from all studies showed mixed
      effects; a high degree of heterogeneity prevented a meta-analysis of findings;
      and none of the studies reported how the potential savings of MDT working may
      offset the costs of administering, preparing for, and attending MDT meetings.
      CONCLUSIONS: Current evidence is insufficient to determine whether MDT working is
      cost-effective or not in secondary care. Further studies aimed at understanding
      the key aspects of MDT working that lead to cost-effective cancer and non-cancer
      care are required.

PMID- 23557142
TI  - Effects of using coding potential, sequence conservation and mRNA structure
      conservation for predicting pyrrolysine containing genes.
AB  - BACKGROUND: Pyrrolysine (the 22nd amino acid) is in certain organisms and under
      certain circumstances encoded by the amber stop codon, UAG. The circumstances
      driving pyrrolysine translation are not well understood. The involvement of a
      predicted mRNA structure in the region downstream UAG has been suggested, but the
      structure does not seem to be present in all pyrrolysine incorporating genes.
      RESULTS: We propose a strategy to predict pyrrolysine encoding genes in genomes
      of archaea and bacteria. We cluster open reading frames interrupted by the amber
      codon based on sequence similarity. We rank these clusters according to several
      features that may influence pyrrolysine translation. The ranking effects of
      different features are assessed and we propose a weighted combination of these
      features which best explains the currently known pyrrolysine incorporating genes.
      We devote special attention to the effect of structural conservation and provide
      further substantiation to support that structural conservation may be influential
      - but is not a necessary factor. Finally, from the weighted ranking, we identify
      a number of potentially pyrrolysine incorporating genes. CONCLUSIONS: We propose
      a method for prediction of pyrrolysine incorporating genes in genomes of bacteria
      and archaea leading to insights about the factors driving pyrrolysine translation
      and identification of new gene candidates. The method predicts known conserved
      genes with high recall and predicts several other promising candidates for
      experimental verification. The method is implemented as a computational pipeline
      which is available on request.

PMID- 23557145
TI  - Dilemmas about the toxicological consequences of metal-on-metal hip prostheses --
      What we do and do not know, and what we should do?

PMID- 23557144
TI  - Slow CCL2-dependent translocation of biopersistent particles from muscle to
      brain.
AB  - BACKGROUND: Long-term biodistribution of nanomaterials used in medicine is
      largely unknown. This is the case for alum, the most widely used vaccine
      adjuvant, which is a nanocrystalline compound spontaneously forming
      micron/submicron-sized agglomerates. Although generally well tolerated, alum is
      occasionally detected within monocyte-lineage cells long after immunization in
      presumably susceptible individuals with systemic/neurologic manifestations or
      autoimmune (inflammatory) syndrome induced by adjuvants (ASIA). METHODS: On the
      grounds of preliminary investigations in 252 patients with alum-associated ASIA
      showing both a selective increase of circulating CCL2, the major monocyte
      chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments
      to assess biodistribution of vaccine-derived aluminum and of alum-particle
      fluorescent surrogates injected in muscle. Aluminum was detected in tissues by
      Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent
      latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used.
      RESULTS: Intramuscular injection of alum-containing vaccine was associated with
      the appearance of aluminum deposits in distant organs, such as spleen and brain
      where they were still detected one year after injection. Both fluorescent
      materials injected into muscle translocated to draining lymph nodes (DLNs) and
      thereafter were detected associated with phagocytes in blood and spleen.
      Particles linearly accumulated in the brain up to the six-month endpoint; they
      were first found in perivascular CD11b+ cells and then in microglia and other
      neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral
      translocation was not observed after direct intravenous injection, but
      significantly increased in mice with chronically altered blood-brain-barrier.
      Loss/gain-of-function experiments consistently implicated CCL2 in systemic
      diffusion of Al-Rho particles captured by monocyte-lineage cells and in their
      subsequent neurodelivery. Stereotactic particle injection pointed out brain
      retention as a factor of progressive particle accumulation. CONCLUSION:
      Nanomaterials can be transported by monocyte-lineage cells to DLNs, blood and
      spleen, and, similarly to HIV, may use CCL2-dependent mechanisms to penetrate the
      brain. This occurs at a very low rate in normal conditions explaining good
      overall tolerance of alum despite its strong neurotoxic potential. However,
      continuously escalating doses of this poorly biodegradable adjuvant in the
      population may become insidiously unsafe, especially in the case of
      overimmunization or immature/altered blood brain barrier or high constitutive CCL
      2 production.

PMID- 23557146
TI  - One single method to produce native and Tat-fused recombinant human alpha
      synuclein in Escherichia coli.
AB  - BACKGROUND: Human alpha-synuclein is a small-sized, natively unfolded protein
      that in fibrillar form is the primary component of Lewy bodies, the pathological
      hallmark of Parkinson's disease. Experimental evidence suggests that alpha
      synuclein aggregation is the key event that triggers neurotoxicity although
      additional findings have proposed a protective role of alpha-synuclein against
      oxidative stress. One way to address the mechanism of this protective action is
      to evaluate alpha-synuclein-mediated protection by delivering this protein inside
      cells using a chimeric protein fused with the Tat-transduction domain of HIV Tat,
      named TAT-alpha-synuclein. RESULTS: A reliable protocol was designed to
      efficiently express and purify two different forms of human alpha-synuclein. The
      synthetic cDNAs encoding for the native alpha-synuclein and the fusion protein
      with the transduction domain of Tat protein from HIV were overexpressed in a
      BL21(DE3) E. coli strain as His-tagged proteins. The recombinant proteins largely
      localized (>= 85%) to the periplasmic space. By using a quick purification
      protocol, based on recovery of periplasmic space content and metal-chelating
      chromatography, the recombinant alpha-synuclein protein forms could be purified
      in a single step to >= 95% purity. Both alpha-synuclein recombinant proteins form
      fibrils and the TAT-alpha-synuclein is also cytotoxic in the micromolar
      concentration range. CONCLUSIONS: To further characterize the molecular
      mechanisms of alpha-synuclein neurotoxicity both in vitro and in vivo and to
      evaluate the relevance of extracellular alpha-synuclein for the pathogenesis and
      progression of Parkinson's disease, a suitable method to produce different high
      quality forms of this pathological protein is required. Our optimized expression
      and purification procedure offers an easier and faster means of producing
      different forms (i.e., both the native and the TAT-fusion form) of soluble
      recombinant alpha-synuclein than previously described procedures.

PMID- 23557147
TI  - An unusual pattern of three major components of the cardiovascular system:
      multimodality imaging and review of the literature.
AB  - INTRODUCTION: Coronary artery anomalies are found in 0.4% to 1.4% of patients who
      undergo coronary angiography. Anomalous origin of left coronary artery from the
      right sinus of Valsava is the rarest, with a reported prevalence of 0.02 -0.03%
      according to angiographic studies. CASE PRESENTATION: We present the rare case of
      a 42-year-old-man suffering from stable angina with unusual development of 3
      major components of the cardiovascular system Coronary angiography revealed an
      anomalous origin of the left coronary artery from the ostium of the right
      coronary artery. Magnetic resonance angiography depicted an anomalous origin of
      the left common carotid artery from the innominate artery and an aneurysm of
      descending thoracic aorta. Coronary computed tomography angiography revealed the
      course of left coronary artery between aortic root and conus arteriosus at the
      level of the right ventricular outflow tract. In this report we attempt to
      highlight the rarity of this vascular anatomy. CONCLUSION: Anomalous origins of
      the coronary arteries are rare, but may cause myocardial ischemia and sudden
      death. Thus, their reliable identification is a matter of paramount importance
      possibly evaluating the effects of therapeutic intervention. Newer imaging
      modalities improve the illumination of vascular system anatomy, shedding light to
      diagnostic dilemmas that come up in daily medical practice.

PMID- 23557148
TI  - Social networking in online support groups for health: how online social
      networking benefits patients.
AB  - An increasing number of online support groups (OSGs) have embraced the features
      of social networking. So far, little is known about how patients use and benefit
      from these features. By implementing the uses-and-gratifications framework, the
      author conducted an online survey with current users of OSGs to examine
      associations among motivation, use of specific features of OSG, and support
      outcomes. Findings suggest that OSG users make selective use of varied features
      depending on their needs, and that perceptions of receiving emotional and
      informational support are associated more with the use of some features than
      others. For example, those with strong motivation for social interaction use
      diverse features of OSG and make one-to-one connections with other users by
      friending. In contrast, those with strong motivation for information seeking
      limit their use primarily to discussion boards. Results also show that online
      social networking features, such as friending and sharing of personal stories on
      blogs, are helpful in satisfying the need for emotional support. The present
      study sheds light on online social networking features in the context of health
      related OSGs and provides practical lessons on how to improve the capacity of
      OSGs to serve the needs of their users. 

PMID- 23557149
TI  - Attention deficit/hyperactivity and comorbid symptoms in preschoolers:
      differences between subgroups in neuropsychological basic deficits.
AB  - BACKGROUND: There is wide agreement on the heterogeneity of attention
      deficit/hyperactivity disorder (ADHD). Subgroups with specific comorbid problems,
      neuropsychological deficits, and developmental trajectories that start in
      preschool years have been assumed. We analyze whether corresponding subgroups at
      risk for ADHD development can be identified in a preschool sample and whether
      these subgroups show the assumed neuropsychological deficits. METHODS: The study
      sample consisted in 141 preschool children (3-6 years; 68 boys), including 41
      children at risk for ADHD development (because of high ADHD symptoms or first
      degree relatives with an ADHD diagnosis). Parent- and teacher-reported symptoms
      of ADHD, ODD/CD, and anxiety/depression were assessed. Cluster analyses were
      conducted on the continuous symptom scores. Inhibitory control and delay aversion
      were measured by six neuropsychological tasks. RESULTS: Cluster analyses resulted
      in four groups. Two of these groups showed high ADHD symptoms - one showing
      multiple comorbid symptoms, one showing hardly any further symptoms. The other
      two groups were characterized by no problems and by some sensorimotor deficits. A
      priori contrasts revealed that the "high comorbidity" cluster showed the worst
      inhibitory control performance while the "pure ADHD symptoms" cluster showed the
      highest delay aversion. CONCLUSION: The ADHD-symptom clusters matched types that
      have been proposed in recent models. This description might help to identify
      different ADHD-related pathways in future longitudinal research.

PMID- 23557150
TI  - Ion-cage interpretation for the structural and dynamic changes of ionic liquids
      under an external electric field.
AB  - In many applications, ionic liquids (ILs) work in a nonequilibrium steady state
      driven by an external electric field. However, how the electric field changes the
      structure and dynamics of ILs and its underlying mechanism still remain poorly
      understood. In this paper, coarse-grained molecular dynamics simulations were
      performed to investigate the structure and dynamics of 1-ethyl-3
      methylimidazolium nitrate ([EMIm][NO3]) under a static electric field. The ion
      cage structure was found to play an essential role in determining the structural
      and dynamic properties of the IL system. With a weak or moderate electric field
      (0-10(7) V/m), the external electric field is too weak to modify the ion cage
      structure in an influential way and thus the changes of structural and dynamic
      properties are negligible. With a strong electric field (10(7)-10(9) V/m)
      applied, ion cages expand and deform apparently, leading to the increase of ion
      mobility and self-diffusion coefficient with electric field, and the self
      diffusion of ions along the electric field becomes faster than the other two
      directions due to the anisotropic deformation of ion cages. In addition, the
      Einstein relation connecting diffusion and mobility breaks down at strong
      electric fields, and it also breaks down for a single ion species even at
      moderate electric fields (linear-response region).

PMID- 23557151
TI  - Cutaneous manifestations in patients with POEMS syndrome.
AB  - BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,
      and skin changes syndrome is a rare multisystem paraneoplastic condition
      associated with plasma cell dyscrasia. METHODS: From our institution's
      dysproteinemia database, 107 patients met criteria for polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome
      between January 1, 2000, and October 1, 2009. Medical records were reviewed for
      documented syndrome features at diagnosis. We assessed prevalence of skin
      findings and associations between dermatologic and other characteristic disease
      findings. RESULTS: Of the 107 patients, 96 (90%) had a recognized cutaneous
      manifestation. Hyperpigmentation and hemangioma were most common (47%), followed
      by hypertrichosis (38%). Vascular skin changes--acrocyanosis (34%), Raynaud
      phenomenon (20%), hyperemia/erythema (20%), flushing (16%), or rubor (11%)-
      occurred in 62%; white nails, sclerodermoid changes, and clubbing occurred in
      30%, 26%, and 6%, respectively. Mean number of skin findings per patient was 2.9
      (median, 3.0; range, 0-7). Presence of cutaneous manifestation was associated
      with abnormal pulmonary function tests (P < 0.001); immunoglobulin G gammopathy
      was associated with hyperpigmentation and hypertrichosis. No other significant
      associations were seen. CONCLUSIONS: The high prevalence of skin findings (90%)
      shows the value of dermatologic evaluation in diagnosis of polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome.
      Our data indicate new associations between skin findings and other disease
      characteristics.

PMID- 23557153
TI  - Asymmetric approach to hyacinthacines B1 and B2.
AB  - Naturally occurring hyacinthacines B1 and B2 have been prepared from a common,
      easily available, advanced intermediate. The approach features several highly
      stereoselective transformations: inter alia, a dichloroketene-enol ether [2 + 2]
      cycloaddition, a Bruylants alkylation, and an amino-nitrile alkylation-reduction.

PMID- 23557152
TI  - Multivariate analysis of brain metabolism reveals chemotherapy effects on
      prefrontal cerebellar system when related to dorsal attention network.
AB  - BACKGROUND: Functional brain changes induced by chemotherapy are still not well
      characterized. We used a novel approach with a multivariate technique to analyze
      brain resting state [18 F]FDG-PET in patients with lymphoma, to explore
      differences on cerebral metabolic glucose rate between chemotherapy-treated and
      non-treated patients. METHODS: PET/CT scan was performed on 28 patients, with 14
      treated with systemic chemotherapy. We used a support vector machine (SVM)
      classification, extracting the mean metabolism from the metabolic patterns, or
      networks, that discriminate the two groups. We calculated the correct
      classifications of the two groups using the mean metabolic values extracted by
      the networks. RESULTS: The SVM classification analysis gave clear-cut patterns
      that discriminate the two groups. The first, hypometabolic network in
      chemotherapy patients, included mostly prefrontal cortex and cerebellar areas
      (central executive network, CEN, and salience network, SN); the second, which is
      equal between groups, included mostly parietal areas and the frontal eye field
      (dorsal attention network, DAN). The correct classification membership to
      chemotherapy or not chemotherapy-treated patients, using only one network, was of
      50% to 68%; however, when all the networks were used together, it reached 80%.
      CONCLUSIONS: The evidenced networks were related to attention and executive
      functions, with CEN and SN more specialized in shifting, inhibition and
      monitoring, DAN in orienting attention. Only using DAN as a reference point,
      indicating the global frontal functioning before chemotherapy, we could better
      classify the subjects. The emerging concept consists in the importance of the
      investigation of brain intrinsic networks and their relations in chemotherapy
      cognitive induced changes.

PMID- 23557154
TI  - Mortality due to pulmonary embolism, myocardial infarction, and stroke among
      incident dialysis patients: a rebuttal.

PMID- 23557155
TI  - Ontogeny of human umbilical cord perivascular cells: molecular and fate potential
      changes during gestation.
AB  - Human umbilical cord-derived perivascular cells (PVCs) are a recently
      characterized source of mesenchymal stromal cells that has gained much interest
      in the field of cellular therapeutics. However, very little is known about the
      changes in fate potential and restrictions that these cells undergo during
      gestational development. This study is the first to examine the phenotypic,
      molecular, and functional properties of first trimester (FTM)-derived PVCs,
      outlining properties that are unique to this population when compared to term
      (TERM) counterparts. FTM- and TERM-PVCs displayed analogous mesenchymal,
      perivascular, and immunological immunophenotypes. Both PVCs could be maintained
      in culture without alteration to these phenotypes or mesenchymal lineage
      differentiation potential. Some unique features of FTM-PVCs were uncovered in
      this study: (1) while the gene signatures of FTM- and TERM-PVCs were similar, key
      differences were observed, namely, that the Oct4A and Sox17 proteins were
      detected in FTM-PVCs, but not in TERM counterparts; (2) FTM-PVCs exhibited a
      greater proliferative potential; and (3) FTM-PVCs were more efficient in their in
      vitro differentiation toward selective mesenchymal cell types, including the
      chondrogenic and adipogenic lineages, as well as toward neuronal- and hepatocyte
      like lineages, when compared to TERM-PVCs. Both PVCs were able to generate
      osteocytes and cardiomyocyte-like cells with similar efficiencies in vitro.
      Overall, FTM-PVCs show more plasticity than TERM-PVCs with regard to fate
      acquisition, suggesting that a restriction in multipotentiality is imposed on
      PVCs as gestation progresses. Taken together, our findings support the idea that
      PVCs from earlier in gestation may be better than later sources of multipotent
      stromal cells (MSCs) for some regenerative medicine applications. 

PMID- 23557156
TI  - In memoriam: Marcia Wilkinson.

PMID- 23557157
TI  - Headache triggers and causality editorial: a research roadmap and clinical
      caution.

PMID- 23557158
TI  - Migraine and cognition.

PMID- 23557159
TI  - (31) P-MRS in migraine: fallen through the cracks.

PMID- 23557160
TI  - New daily persistent headache: disease or syndrome?

PMID- 23557161
TI  - Response letter: new daily persistent headache: disease or syndrome?

PMID- 23557162
TI  - Including mood in the proposed criteria for refractory migraine.

PMID- 23557163
TI  - Headache medicine meets neuro-ophthalmology: exam techniques and challenging
      cases.
AB  - The neuro-ophthalmology examination is critical to anyone who sees patients with
      the common symptom of headache. By examining the visual acuity, pupils, visual
      fields, motility, and fundus, clues to both secondary causes of headache and
      primary headaches exist. In this review, we discuss how to do the neuro
      ophthalmology examination and we review cases of primary and secondary headache
      where key features of the examination assisted in making the correct diagnosis.

PMID- 23557164
TI  - Migraine and obesity.

PMID- 23557167
TI  - The immediate impact of the Fukushima Daiichi accident on local property values.
AB  - The Fukushima Daiichi accident released huge amounts of radioactive material over
      a wide area. We can appreciate the geographical extent of radioactive
      contamination from the information published online by the Japanese government.
      Historically, this is an unprecedented situation, which allows "natural
      experimentation" to estimate the causal effects of radioactive contamination on
      our society. This study focused on property value losses caused by the accident
      and analyzed changes in land appraisals around the Fukushima Daiichi plant from
      July 2010 to July 2011 within the framework of hedonic approach. Thus, we
      estimated the short-run impact of the contamination or the change in marginal
      value of proximity to the plant. The results suggest that the appraisals
      significantly and monotonically depreciated with increasing contamination levels.
      However, there was no evidence to suggest changes in the marginal value of
      proximity to the plant. A comparison between the appraisals and transaction
      prices indicates that this result could be interpreted as an underestimate of
      actual property value losses. 

PMID- 23557166
TI  - First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in
      pregnant women with and without preeclampsia.
AB  - BACKGROUND: First trimester Pregnancy Associated Plasma Protein A (PAPP-A)
      levels, routinely measured for aneuploidy screening, may predict development of
      preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels
      correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic
      marker associated with preeclampsia, throughout pregnancy. METHODS: sFlt-1 levels
      were measured longitudinally in 427 women with singleton pregnancies in all three
      trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were
      measured. Student's T and Wilcoxon tests compared preeclamptic and normal
      pregnancies. A linear mixed model assessed the relationship between log PAPP-A
      and serial log sFlt-1 levels. RESULTS: PAPP-A and PAPP-A MOM levels were
      significantly lower in preeclamptic (n = 19), versus normal pregnancies (p =
      0.02). Although mean third trimester sFlt-1 levels were significantly higher in
      preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who
      developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A
      levels correlated significantly with serial sFlt-1 levels. Importantly, low first
      trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p =
      0.002). CONCLUSIONS: Low first trimester PAPP-A levels suggests increased future
      risk of preeclampsia and correlate with serial sFlt-1 levels throughout
      pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted
      decreased odds of normal pregnancy.

PMID- 23557169
TI  - Janus particles: synthesis, self-assembly, physical properties, and applications.

PMID- 23557168
TI  - Colloidal CdSe/Cu3P/CdSe nanocrystal heterostructures and their evolution upon
      thermal annealing.
AB  - We report the synthesis of colloidal CdSe/Cu(3)P/CdSe nanocrystal
      heterostructures grown from hexagonal Cu(3)P platelets as templates. One type of
      heterostructure was a sort of "coral", formed by vertical pillars of CdSe grown
      preferentially on both basal facets of a Cu(3)P platelet and at its edges.
      Another type of heterostructure had a "sandwich" type of architecture, formed by
      two thick, epitaxial CdSe layers encasing the original Cu(3)P platelet. When the
      sandwiches were annealed under vacuum up to 450  degrees C, sublimation of P and
      Cd species with concomitant interdiffusion of Cu and Se species was observed by
      in situ HR- and EFTEM analyses. These processes transformed the starting
      sandwiches into Cu2Se nanoplatelets. Under the same conditions, both the pristine
      (uncoated) Cu(3)P platelets and a control sample made of isolated CdSe
      nanocrystals were stable. Therefore, the thermal instability of the sandwiches
      under vacuum might be explained by the diffusion of Cu species from Cu(3)P cores
      into CdSe domains, which triggered sublimation of Cd, as well as out-diffusion of
      P species and their partial sublimation, together with the overall transformation
      of the sandwiches into Cu(2)Se nanocrystals. A similar fate was followed by the
      coral-like structures. These CdSe/Cu(3)P/CdSe nanocrystals are therefore an
      example of a nanostructure that is thermally unstable, despite its separate
      components showing to be stable under the same conditions.

PMID- 23557170
TI  - Efficacy of Essure hysteroscopic sterilization--5 years follow up of 1200 women.
AB  - OBJECTIVE: To assess the efficacy of the Essure hysteroscopic birth control
      device after 5 years follow up. STUDY DESIGN: Retrospective analysis of case
      series. SETTING: Outpatient hysteroscopy facility in a large teaching hospital.
      SUBJECTS: One-thousand three-hundred and twenty-one women who underwent
      hysteroscopic sterilization with Essure device (Conceptus, Inc., Mountain View,
      CA) between January 2003 and May 2005. INTERVENTION(S): Hysteroscopic tubal
      sterilization using Essure system. MAIN OUTCOME MEASURE: Efficacy/effectiveness,
      failure rate. RESULTS: Satisfactory insertion was accomplished in the first
      attempt in 1166 women (97.16%). After the second attempt, successful insertion
      rate rise to 98.6%. (n = 31, 2.6%). Three pregnancies had been reported after 5
      years follow up, which implies an overall absolute rate of 0.25%. This represents
      a Pearl index of 0.05 after 72,000 months of surveillance. All of them occurred
      in the first year of use of the microinsert. There has been no unintended
      pregnancy in the next 4 years. CONCLUSION(S): Essure has the lowest Pearl index
      never published being the most effective permanent birth control system to date.
      Unintended pregnancies tend to occur in the first year after the insertion, and
      can be avoided encouraging women to accomplish the protocol.

PMID- 23557171
TI  - Left atrial functional remodeling in lone atrial fibrillation: a two-dimensional
      speckle tracking echocardiographic study.
AB  - OBJECTIVE: The aim of this study was to assess left atrial (LA) functional
      remodeling in lone atrial fibrillation (LAF) patients via two-dimensional speckle
      tracking echocardiography (2DSTE). METHODS: Forty-five paroxysmal LAF patients
      and 30 healthy controls underwent 2DSTE in sinus rhythm. Longitudinal LA
      strain/strain rate (LAS/LASR) of booster, reservoir, and conduit function in
      apical four- and two-chamber views were measured and averages of the 2 views were
      used. RESULTS: The 2 groups had similarity in LA volume. LAS and LASR of the 3
      phasic functions were reduced in patients. Comparing the 2 groups, LA booster
      strain (LASa) and strain rate were -12.31 +/- 3.15 versus -15.30 +/- 2.52% and 
      1.64 +/- 0.51 versus -2.08 +/- 0.48 1/sec, respectively, P < 0.05 for both.
      Multivariate regression confirmed that LAF was an independent determinant of
      LAS/LASR reduction. LASa was the most accurate parameter for differentiating LAF
      patients from controls (area under receiver operating characteristic curve,
      0.763; cutoff value, -14.3%; sensitivity, 71.1% and specificity, 70.0%). Finally,
      LASa decrement was found to be the only significant predictor of early atrial
      fibrillation (AF) recurrence (odds ratio [OR], 1.39 per unit decrement; 95% CI,
      1.02-1.89; P = 0.038). CONCLUSIONS: Remodeling of LA booster pump, reservoir, and
      conduit function in LAF patients can be detected by 2DSTE before structural
      remodeling. Occurrence of LAF is associated with impairment of LA intrinsic
      myocardial properties. LASa can differentiate LAF patients and lower LASa is
      associated with early recurrence of AF after ablation.

PMID- 23557173
TI  - Effect of triflumuron, a chitin synthesis inhibitor, on Aedes aegypti, Aedes
      albopictus and Culex quinquefasciatus under laboratory conditions.
AB  - BACKGROUND: Resistance to traditional insecticides represents a threat to the
      control of disease vectors. The insect growth regulators (IGR) are a potential
      alternative to control mosquitoes, including resistant populations. The chitin
      synthesis inhibitors (CSI) are IGRs, which interfere with the insect molting
      process and represent one major class of compounds against Aedes aegypti
      populations resistant to the larvicide organophosphate temephos. In the present
      study, we evaluated the efficacy of the CSI triflumuron on Culex
      quinquefasciatus, Aedes albopictus and against several Ae. aegypti field
      populations. METHODS: The efficacy of triflumuron, against Cx. quinquefasciatus
      and Ae. albopictus was evaluated with laboratory strains through dose-response
      assays. Additionaly, this CSI was tested against seven Ae. aegypti field
      populations exhibiting distinct resistance levels to both temephos and the
      pyrethroid deltamethrin. Aedes aegypti populations were exposed to both a dose
      that inhibits 99% of the adult emergence of mosquitoes from the susceptible
      reference strain, Rockefeller, (EI99 = 3.95 MUg/L) and the diagnostic dose (DD),
      corresponding to twice the EI99. RESULTS: Our results indicate that triflumuron
      was effective in emergence inhibition (EI) of Cx. quinquefasciatus (EI50 = 5.28
      MUg/L; EI90= 12.47 MUg/L) and Ae. albopictus (EI50 = 1.59 MUg/L; EI90= 2.63
      MUg/L). Triflumuron was also effective against seven Ae. aegypti Brazilian
      populations resistant to both temephos and deltamethrin. Exposure of all the Ae.
      aegypti populations to the triflumuron EI99 of the susceptible reference strain,
      Rockefeller, resulted in complete inhibition of adult emergence, suggesting no
      cross-resistance among traditional insecticides and this CSI. However, a positive
      correlation between temephos resistance and tolerance to triflumuron was
      observed. CONCLUSION: The results suggest that triflumuron represents a potential
      tool for the control of disease vectors in public health. Nevertheless, they
      point to the need of constant monitoring of the susceptibility status of vector
      populations to CSIs.

PMID- 23557172
TI  - HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with
      advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial.
AB  - BACKGROUND: Human papilloma virus type 16 (HPV16)-induced gynecological cancers,
      in particular cervical cancers, are found in many women worldwide. The HPV16
      encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune
      system permitting the development of an HPV16-synthetic long peptide (SLP)
      vaccine with an excellent treatment profile in animal models. Here, we determined
      the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in
      patients with advanced or recurrent HPV16-induced gynecological carcinoma.
      METHODS: Patients with HPV16-positive advanced or recurrent gynecological
      carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine
      consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in
      Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor
      regression as determined by RECIST. In addition, the vaccine-induced T-cell
      response was assessed by proliferation and associated cytokine production as well
      as IFNgamma-ELISPOT. RESULTS: No systemic toxicity beyond CTCAE grade II was
      observed. In a few patients transient flu-like symptoms were observed. In 9 out
      of 16 tested patients vaccine-induced HPV16-specific proliferative responses were
      detected which were associated with the production of IFNgamma, TNFalpha, IL-5
      and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11
      of the 13 tested patients. The capacity to respond to the vaccine was positively
      correlated to the patient's immune status as reflected by their response to
      common recall antigens at the start of the trial. Median survival was 12.6 +/-
      9.1 months. No regression of tumors was observed among the 12 evaluable patients.
      Nineteen patients died of progressive disease. CONCLUSIONS: The HPV16-SLP vaccine
      was well tolerated and induced a broad IFNgamma-associated T-cell response in
      patients with advanced or recurrent HPV16-induced gynecological carcinoma but
      neither induced tumor regression nor prevented progressive disease. We,
      therefore, plan to use this vaccine in combination with chemotherapy and
      immunomodulation.

PMID- 23557174
TI  - Twist2 functions as a tumor suppressor in murine osteosarcoma cells.
AB  - The epithelial-mesenchymal transition (EMT) contributes to the malignant
      progression of cancer cells including acquisition of the ability to undergo
      metastasis. However, whereas EMT-related transcription factors (EMT-TF) are known
      to play an important role in the malignant progression of epithelial tumors,
      their role in mesenchymal tumors remains largely unknown. We show that expression
      of the gene for Twist2 is downregulated in human osteosarcoma and correlates
      inversely with tumorigenic potential in mouse osteosarcoma. Forced expression of
      Twist2 in highly tumorigenic murine osteosarcoma cells induced a slight
      inhibition of cell growth in vitro but markedly suppressed tumor formation in
      vivo. Conversely, knockdown of Twist2 in osteosarcoma cells with a low
      tumorigenic potential promoted tumor formation in vivo, suggesting that Twist2
      functions as a tumor suppressor in osteosarcoma cells. Furthermore, Twist2
      induced expression of fibulin-5, which has been reported as a tumor suppressor.
      Medium conditioned by mouse osteosarcoma cells overexpressing Twist2 inhibited
      expression of the MMP9 gene as well as invasion in mouse embryonic fibroblasts,
      and forced expression of Twist2 in osteosarcoma cells suppressed MMP9 gene
      expression in tumor tissue. Data from the present study suggest that Twist2
      inhibits formation of a microenvironment conducive to tumor growth and thereby
      attenuates tumorigenesis in osteosarcoma. 

PMID- 23557177
TI  - Subcutaneous administration of nano- and microsuspensions of poorly soluble
      compounds to rats.
AB  - The aim of the present study was to evaluate and interpret the pharmacokinetic
      profiles of two compounds after subcutaneous (s.c.) administration. The compounds
      have similar physicochemical properties, but are a base (BA99) and an acid
      (AC88), respectively. The compounds were administered as nano- (5 and 500
      umol/kg) and microsuspensions (5 umol/kg) s.c. to Sprague-Dawley rats. At the low
      dose, the exposure was higher for both compounds administered as nanocrystals
      compared to microparticles. The high dose of the compounds resulted in even
      higher exposure, but not in a dose-linear manner. The differences in exposure
      between nano- and microparticles were mainly ascribed to higher dissolution rate
      and improved solubility for smaller particles. In addition to differences in
      exposure, there were also differences in the elimination pattern. After s.c.
      injection of 5 umol/kg of BA99 as nano- and microsuspensions, the elimination
      profile was similar as observed earlier after oral administration. However, after
      injection of the higher dose of BA99 and all formulations of AC88, an extended
      elimination profile was observed, forming a maintained plateau under the
      investigated time-period. Essentially, constant plasma levels were caused by a
      balanced equilibrium between total body clearance of the drug and supply rate of
      drug from the formulations.

PMID- 23557179
TI  - Reexpansion pulmonary edema after treatment of simultaneous bilateral spontaneous
      tension pneumothorax.
AB  - We report a case of 46-year-old male with simultaneous bilateral spontaneous
      tension pneumothorax. Severe reexpansion pulmonary edema developed after
      bilateral tube thoracoscomy, but he was recovered after 2 days ventilator care.
      After bilateral wedge resection and talc pleurodesis, he was discharged without
      complications and had remained well and without recurrence during the 8-year
      follow-up.

PMID- 23557178
TI  - Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory
      response, astroglial reactivity and complex behavioral changes.
AB  - BACKGROUND: Diffuse traumatic axonal injury (TAI), a common consequence of
      traumatic brain injury, is associated with high morbidity and mortality.
      Inflammatory processes may play an important role in the pathophysiology of TAI.
      In the central fluid percussion injury (cFPI) TAI model in mice, the
      neuroinflammatory and astroglial response and behavioral changes are unknown.
      METHODS: Twenty cFPI-injured and nine sham-injured mice were used, and the
      neuroinflammatory and astroglial response was evaluated by immunohistochemistry
      at 1, 3 and 7 days post-injury. The multivariate concentric square field test
      (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI
      (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric
      statistics and principal component analysis (MCSF data). RESULTS: At all post
      injury time points, beta-amyloid precursor protein (beta-APP) immunoreactivity
      revealed widespread bilateral axonal injury and IgG immunostaining showed
      increased blood-brain barrier permeability. Using vimentin and glial fibrillary
      acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in
      cortical regions and important white matter tracts peaking at three days post
      injury. Only vimentin was increased post-injury in the internal capsule and only
      GFAP in the thalamus. Compared to sham-injured controls, an increased number of
      activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3)
      appearing one day after TAI (P<0.05 for all cell types) was observed in
      subcortical white matter. In the MCSF, the behavioral patterns including general
      activity and exploratory behavior differed between cFPI mice and sham-injured
      controls. CONCLUSIONS: Traumatic axonal injury TAI resulted in marked bilateral
      astroglial and neuroinflammatory responses and complex behavioral changes. The
      cFPI model in mice appears suitable for the study of injury mechanisms, including
      neuroinflammation, and the development of treatments targeting TAI.

PMID- 23557180
TI  - Insights into biodiversity sampling strategies for freshwater microinvertebrate
      faunas through bioblitz campaigns and DNA barcoding.
AB  - BACKGROUND: Biodiversity surveys have long depended on traditional methods of
      taxonomy to inform sampling protocols and to determine when a representative
      sample of a given species pool of interest has been obtained. Questions remain as
      to how to design appropriate sampling efforts to accurately estimate total
      biodiversity. Here we consider the biodiversity of freshwater ostracods
      (crustacean class Ostracoda) from the region of Churchill, Manitoba, Canada.
      Through an analysis of observed species richness and complementarity,
      accumulation curves, and richness estimators, we conduct an a posteriori analysis
      of five bioblitz-style collection strategies that differed in terms of total
      duration, number of sites, protocol flexibility to heterogeneous habitats,
      sorting of specimens for analysis, and primary purpose of collection. We used DNA
      barcoding to group specimens into molecular operational taxonomic units for
      comparison. RESULTS: Forty-eight provisional species were identified through
      genetic divergences, up from the 30 species previously known and documented in
      literature from the Churchill region. We found differential sampling efficiency
      among the five strategies, with liberal sorting of specimens for molecular
      analysis, protocol flexibility (and particularly a focus on covering diverse
      microhabitats), and a taxon-specific focus to collection having strong influences
      on garnering more accurate species richness estimates. CONCLUSIONS: Our findings
      have implications for the successful design of future biodiversity surveys and
      citizen-science collection projects, which are becoming increasingly popular and
      have been shown to produce reliable results for a variety of taxa despite relying
      on largely untrained collectors. We propose that efficiency of biodiversity
      surveys can be increased by non-experts deliberately selecting diverse
      microhabitats; by conducting two rounds of molecular analysis, with the numbers
      of samples processed during round two informed by the singleton prevalence during
      round one; and by having sub-teams (even if all non-experts) focus on select
      taxa. Our study also provides new insights into subarctic diversity of freshwater
      Ostracoda and contributes to the broader "Barcoding Biotas" campaign at
      Churchill. Finally, we comment on the associated implications and future research
      directions for community ecology analyses and biodiversity surveys through DNA
      barcoding, which we show here to be an efficient technique enabling rapid
      biodiversity quantification in understudied taxa.

PMID- 23557181
TI  - Effects of responsibility attribution and message source on young adults' health
      attitudes and behaviors.
AB  - This study investigated the effect of message attributes on responses to health
      messages. The authors examined 3 variables--responsibility attribution
      (individual vs. social), source (personal blog vs. online magazine), and illness
      (stigmatized vs. nonstigmatized)--for effects on young adults' health-related
      attitudes and behaviors. Responsibility attributions influenced attitudes about
      individual responsibility for health but did not alter participants' behavioral
      intentions. Further, individuals exposed to a story from a health magazine
      exhibited stronger intentions to communicate about health than individuals
      exposed to a personal health blog. Although women's attitudes regarding social
      responsibility for health did not differ by illness type or responsibility
      attribution, men's attitudes did.

PMID- 23557182
TI  - Cutaneous metastasis: clinicopathological study of 72 patients from a tertiary
      care center in Lebanon.
AB  - BACKGROUND: Cutaneous metastasis is the result of malignant cell spread from
      primary malignancy to the skin. This is not uncommon, and rates reported in the
      literature are as high as 10.4%. To the best of our knowledge, there are no
      studies assessing the epidemiologic, clinical, and histopathological features of
      cutaneous metastasis in our region. OBJECTIVE: To assess the clinical and
      histopathological findings of all patients diagnosed with cutaneous metastasis at
      the American University of Beirut - Medical Center (AUB-MC) and to compare our
      findings with those published in the literature. METHODS: Retrospective clinical
      and histopathologic evaluation of all cases diagnosed as cutaneous metastasis at
      AUB-MC between 1992 and 2010. RESULTS: A total of 72 patients (50 females and 22
      males) were identified. The mean age at diagnosis was 55.2 years. The most common
      primary cancer was breast cancer in women and laryngeal cancer in men. The most
      common clinical presentation was a single nodule in 27% of cases followed by
      multiple nodules in 23%. Cutaneous metastasis lesions were asymptomatic in the
      majority. The chest was the most commonly affected site. On microscopy, the
      majority of metastatic cases were adenocarcinomas (74%). CONCLUSION: This is, to
      our knowledge, the first study characterizing the epidemiological, clinical, and
      histopathological features of cutaneous metastasis in the Lebanese population.
      The clinical and histopathological features observed were in concordance with the
      published literature, with minor differences.

PMID- 23557183
TI  - Successful radioimmunotherapy of established syngeneic rat colon carcinoma with
      211At-mAb.
AB  - BACKGROUND: Most carcinomas are prone to metastasize despite successful treatment
      of the primary tumor. One way to address this clinical challenge may be targeted
      therapy with alpha-emitting radionuclides such as astatine-211 (211At).
      Radioimmunotherapy utilizing alpha-particle emitting radionuclides is considered
      especially suitable for the treatment of small cell clusters and single cells,
      although lesions of different sizes may also be present in the patient. The aim
      of this study was primarily to evaluate the toxicity and secondarily in vivo
      efficacy of a 211At-labeled monoclonal antibody (mAb) directed against colon
      carcinoma with tumor diameters of approximately 10 mm. METHODS: Eighteen rats
      with subperitoneal syngeneic colon carcinoma were allocated to three groups of
      six animals together with three healthy rats in each group. The groups were
      injected intravenously with either 150 MUg of unlabeled mAbs (controls) or 2.5 or
      5 MBq 211At-mAbs directed towards the Lewis Y antigen expressed on the cell
      membrane of several carcinomas. Tumor volume, body weight, and blood cell counts
      were monitored for 100 days after treatment. RESULTS: Local tumors were non
      palpable in five out of six rats after treatment with both activities of 211At
      mAbs, compared to one out of six in the control group. At the study end, half of
      the animals in each group given 211At-BR96 and one animal in the control group
      were free from disease. Radioimmunotherapy resulted in dose-dependent, transient
      weight loss and myelotoxicity. Survival was significantly better in the groups
      receiving targeted alpha therapy than in those receiving unlabeled mAbs.
      CONCLUSIONS: This study demonstrates the possibility of treating small, solid
      colon carcinoma tumors with alpha-emitting radionuclides such as 211At bound to
      mAbs, with tolerable toxicity.

PMID- 23557185
TI  - Hydration of lysozyme studied by Raman spectroscopy.
AB  - Hydration plays a fundamental role in maintaining the three-dimensional structure
      and function of proteins. In this study, Raman spectroscopy was used to probe the
      hydration induced structural changes at various sites of lysozyme under
      isothermal conditions in the range of water contents from 0 to 44 wt %. Raman
      hydration curves were constructed from detailed analysis of marker bands.
      Transition inflection points (w(m)) and onsets determined from the hydration
      curves have shown that structural changes start at 7-10 and end at about 35 wt %
      water. The onset of structural changes coincides with the onset of the broad
      glass transition earlier observed in this system. The increase of alpha-helix
      content starts at very low concentrations of water with w(m) = 12 wt %.
      Monitoring the development of importance for enzymatic action hydrophobic
      clusters has revealed wm = 15 wt % and completion of the process at 25 wt %. The
      parameters of 621 cm(-1) (Phe) and 1448 cm(-1) (CH2 bending) modes were found to
      be sensitive to hydration, suggesting changes in organization of water molecules
      near the protein surface. The native structure of lysozyme was achieved at 35 wt
      % water where its content is high enough for filling the space between lysozyme
      molecules.

PMID- 23557184
TI  - Dose- and time-dependent neuroprotective effects of Pycnogenol following
      traumatic brain injury.
AB  - After traumatic brain injury (TBI), both primary and secondary injury cascades
      are initiated, leading to neuronal death and cognitive dysfunction. We have
      previously shown that the combinational bioflavonoid, Pycnogenol (PYC), alters
      some secondary injury cascades and protects synaptic proteins when administered
      immediately following trauma. The purpose of the present study was to explore
      further the beneficial effects of PYC and to test whether it can be used in a
      more clinically relevant fashion. Young adult male Sprague-Dawley rats were
      subjected to a unilateral moderate/severe cortical contusion. Subjects received a
      single intravenous (i.v.) injection of PYC (1, 5, or 10 mg/kg) or vehicle, with
      treatment initiated at 15 min, 2 h, or 4 h post injury. All rats were killed at
      96 h post TBI. Both the cortex and hippocampus ipsilateral and contralateral to
      the injury were evaluated for possible changes in oxidative stress
      (thiobarbituric acid reactive species; TBARS) and both pre- and post-synaptic
      proteins (synapsin-I, synaptophysin, drebrin, post synaptic density protein-95,
      and synapse associated protein-97). Following TBI, TBARS were significantly
      increased in both the injured cortex and ipsilateral hippocampus. Regardless of
      the dose and delay in treatment, PYC treatment significantly lowered TBARS. PYC
      treatment significantly protected both the cortex and hippocampus from injury
      related declines in pre- and post-synaptic proteins. These results demonstrate
      that a single i.v. treatment of PYC is neuroprotective after TBI with a
      therapeutic window of at least 4 h post trauma. The natural bioflavonoid PYC may
      provide a possible therapeutic intervention in neurotrauma.

PMID- 23557187
TI  - Diastereoselective synthesis of complex cis-hexahydroindanes by reductive
      alkylation.
AB  - An efficient and operationally simple approach to complex cis-hexahydroindanes is
      reported. Upon Birch reduction of unprotected, C4-alkylated tetrahydroindanols
      and electrophilic trapping of the tetrasubstituted enolate, cis-fused products
      are formed with a new stereogenic quaternary carbon. The reaction is convergent,
      completely diastereoselective, and shows a broad scope with regard to the
      electrophile.

PMID- 23557186
TI  - Characteristics of mesenchymal stem cells isolated from bone marrow of giant
      panda.
AB  - In present study, we report on bone marrow (BM) mesenchymal stem cells (MSCs)
      that are isolated from giant pandas. Cells were collected from the BM of two
      stillborn giant pandas. The cells were cultured and expanded in 10% fetal bovine
      serum medium. Cell morphology was observed under an inverted microscopy, and the
      proliferation potential of the cells was evaluated by counting cell numbers for
      eight consecutive days. Differentiation potentials of the cells were determined
      by using a variety of differentiation protocols for osteocytes, adipocytes,
      neuron cells, and cardiomyocytes. Meanwhile, the specific gene expressions for
      MSCs or differentiated cells were analyzed by RT-PCR. The isolated cells
      exhibited a fibroblast-like morphology; expressed mesenchymal specific markers
      such as cluster of differentiation 73 (CD73), SRY (sex determining region Y)-box
      2 (SOX-2), guanine nucleotide-binding protein-like 3 (GNL3), and stem cell factor
      receptor (SCFR); and could be differentiated into osteocytes and adipocytes that
      were characterized by Alizarin Red and Oil Red O staining. Under appropriate
      induction conditions, these cells were also able to differentiate into neuroglial
      like or myocardial-like cells that expressed specific myocardial markers such as
      GATA transcription factors 4 (GATA-4), cardiac troponin T (cTnT), and myosin
      heavy chain 7B (MYH7B), or neural specific markers such as Nestin and glial
      fibrillary acidic protein (GFAP). This study demonstrated stem cells recovery and
      growth from giant pandas. The findings suggest that cells isolated from the BM of
      giant pandas have a high proliferative capacity and multiple differentiation
      potential in vitro which might aid conservation efforts. 

PMID- 23557188
TI  - Endogenous t-PA-antigen is an independent predictor of adverse cardiovascular
      events and all-cause death in patients with atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with raised levels of P
      selectin and an apparent prothrombotic state. However, levels of tissue
      plasminogen activator (t-PA)-antigen are increased also. We investigated whether
      high levels of endogenous t-PA-antigen or soluble P-Selectin (sP-Selectin),
      independently of CHADS(2-) or CHA(2) DS(2) VASc-scores, predict major adverse
      cardiovascular events (MACE) in patients with AF when treated according to
      current guidelines. METHODS: This prospective, longitudinal single-center study
      included 269 patients with AF. Blood samples were analyzed for sP-Selectin and t
      PA-antigen concentration by means of commercially available enzyme-linked
      immunoassays. RESULTS: Patients were followed for a median duration of 1933 (1517
      2277) days, during which 78 MACE and 82 deaths occurred. In multivariable
      analyses t-PA-antigen above the median of 4.22 ng mL(-1) was associated with MACE
      and all-cause death (HR 2.55 [1.43-4.57]; P = 0.002) and (HR 2.54 [1.38-4.68]; P
      = 0.003), respectively. There was no association of sP-Selectin with MACE or all
      cause death. Furthermore, t-PA-antigen above the median independently of the
      CHADS(2-) or CHA(2) DS(2) VASc-scores predicted MACE and all-cause death. In
      patients with low and intermediate-risk for cardiovascular events according to
      the CHADS(2)-score the addition of high t-PA-antigen levels (> 4.22 ng mL(-1) )
      had a significant impact on the patients' outcome (low-risk group, HR 3.25 [1.13
      9.38]; P = 0.029 and intermediate-risk group, HR 2.33 [1.27-4.26]; P = 0.006,
      respectively). CONCLUSION: High endogenous t-PA-antigen independently predicts
      MACE and all-cause death in patients with AF. Accordingly, t-PA-antigen as an
      indicator of a prothrombotic state represents a novel biomarker, which might add
      to risk stratification in patients with AF.

PMID- 23557189
TI  - Response to Simsek et al.

PMID- 23557191
TI  - The effect of parity on expenditures for individuals with severe mental illness.
AB  - OBJECTIVE: To determine whether comprehensive behavioral health parity leads to
      changes in expenditures for individuals with severe mental illness (SMI), who are
      likely to be in greatest need for services that could be outside of health plans'
      traditional limitations on behavioral health care. DATA SOURCES/STUDY SETTING: We
      studied the effects of a comprehensive parity law enacted by Oregon in 2007.
      Using claims data, we compared expenditures for individuals in four Oregon
      commercial plans from 2005 through 2008 to a group of commercially insured
      individuals in Oregon who were exempt from parity. STUDY DESIGN: We used
      difference-in-differences and difference-in-difference-in-differences analyses to
      estimate changes in spending, and quantile regression methods to assess changes
      in the distribution of expenditures associated with parity. PRINCIPAL FINDINGS:
      Among 2,195 individuals with SMI, parity was associated with increased
      expenditures for behavioral health services of $333 (95 percent CI $67, $615),
      without corresponding increases in out-of-pocket spending. The increase in
      expenditures was primarily attributable to shifts in the right tail of the
      distribution. CONCLUSIONS: Oregon's parity law led to higher average expenditures
      for individuals with SMI. Parity may allow individuals with high mental health
      needs to receive services that may have been limited without parity regulations.

PMID- 23557192
TI  - Decision making for group risk reduction: dealing with epistemic uncertainty.
AB  - Group risk is usually represented by FN curves showing the frequency of different
      accident sizes for a given activity. Many governments regulate group risk through
      FN criterion lines, which define the tolerable location of an FN curve. However,
      to compare different risk reduction alternatives, one must be able to rank FN
      curves. The two main problems in doing this are that the FN curve contains
      multiple frequencies, and that there are usually large epistemic uncertainties
      about the curve. Since the mid 1970s, a number of authors have used the concept
      of "disutility" to summarize FN curves in which a family of disutility functions
      was defined with a single parameter controlling the degree of "risk aversion."
      Here, we show it to be risk neutral, disaster averse, and insensitive to
      epistemic uncertainty on accident frequencies. A new approach is outlined that
      has a number of attractive properties. The formulation allows us to distinguish
      between risk aversion and disaster aversion, two concepts that have been confused
      in the literature until now. A two-parameter family of disutilities generalizing
      the previous approach is defined, where one parameter controls risk aversion and
      the other disaster aversion. The family is sensitive to epistemic uncertainties.
      Such disutilities may, for example, be used to compare the impact of system
      design changes on group risks, or might form the basis for valuing reductions in
      group risk in a cost-benefit analysis. 

PMID- 23557190
TI  - The impact of tubal ectopic pregnancy in Papua New Guinea--a retrospective case
      review.
AB  - BACKGROUND: Ectopic pregnancy (EP) is an important cause of morbidity and
      mortality amongst women of reproductive age. Tubal EP is well described in
      industrialised countries, but less is known about its impact in low-resource
      countries, in particular in the South Pacific Region. METHODS: We undertook a
      retrospective review of women with tubal EP treated at a provincial referral
      hospital in coastal Papua New Guinea over a period of 56 months. Demographic and
      clinical variables were obtained from patients' medical records and analysed. The
      institutional rate of tubal EP was calculated, and diagnosis and management
      reviewed. Potential risk factors for tubal EP were identified, and delays
      contributing to increased morbidity described. RESULTS: A total of 73 women had
      tubal EP. The institutional rate of tubal EP over the study period was 6.3 per
      1,000 deliveries. There were no maternal deaths due to EP. The mean age of women
      was 31.5+/-5.7 years, 85% were parous, 67% were rural dwellers and 62% had a
      history of sub-fertility. The most commonly used diagnostic aid was
      culdocentesis. One third of women had clinical evidence of shock on arrival. All
      women with tubal EP were managed by open salpingectomy. Tubal rupture was
      confirmed for 48% of patients and was more common amongst rural dwellers. Forty
      three percent of women had macroscopic evidence of pelvic infection. Two-thirds
      of patients received blood transfusions, and post-operative recovery lasted six
      days on average. Late presentation, lack of clinical suspicion, and delays with
      receiving appropriate treatments were observed. CONCLUSIONS: Tubal EP is a common
      gynaecological emergency in a referral hospital in coastal PNG, and causes
      significant morbidity, in particular amongst women residing in rural areas.
      Sexually transmitted infections are likely to represent the most important risk
      factor for tubal EP in PNG. Interventions to reduce the morbidity due to tubal EP
      include the prevention, detection and treatment of sexually transmitted
      infections, identification and reduction of barriers to prompt presentation,
      increasing health workers' awareness of ectopic pregnancy, providing pregnancy
      test kits to rural health centres, and strengthening hospital blood transfusion
      services, including facilities for autotransfusion.

PMID- 23557193
TI  - Cognate Effects and Executive Control in a Patient With Differential Bilingual
      Aphasia.
AB  - We describe a case study of a French-Dutch bilingual patient with differential
      aphasia, showing clearly larger impairments in Dutch than in French. We
      investigated whether this differential impairment in both languages was due to
      selective damage to language-specific brain areas resulting in the "loss" of the
      language representation itself, or rather if it reflects an executive control
      deficit. We assessed cross-linguistic interactions (involving lexical activation
      in the most affected language) with cognates in a lexical decision (LD) task, and
      executive control using a flanker task. We used a generalized LD task (any word
      requires a "yes" response) and a selective LD task in the patient's two languages
      (only words in a given target language require a "yes" response). The cognate
      data unveil a differential pattern in the three tasks, with a clear cognate
      facilitation effect in the generalized LD tasks and almost no cognate effect in
      the selective LD tasks. This implies that a more impaired language can still
      affect the processing of words in the best-preserved language, but only with low
      cross-language competition demands (generalized LD). Additionally, the flanker
      task showed a larger congruency effect for the patient compared with controls,
      indicating cognitive control difficulties. Together, these results support
      accounts of differential bilingual aphasia in terms of language-control
      difficulties.

PMID- 23557194
TI  - Sequencing CTLA-4 blockade with cell-based immunotherapy for prostate cancer.
AB  - BACKGROUND: The FDA recently approved an anti-CTLA-4 antibody (Iplimumab) for the
      treatment of metastatic melanoma. This decision was based on Phase III results,
      which demonstrate that blocking this immune checkpoint provides a survival
      advantage in patients with advanced disease. As a single agent, ipilimumab is
      also being clinically evaluated in advanced (metastatic, castrate-resistant)
      prostate cancer and two randomized, placebo-controlled Phase III studies have
      recently completed accrual. METHODS: We used a well-described genetically
      engineered mouse (GEM), autochronous prostate cancer model (Pro-TRAMP) to explore
      the relative sequencing and dosing of anti-CTLA-4 antibody when combined with a
      cell-based, GM-CSF-secreting vaccine (GVAX). RESULTS: Our results show that
      combined treatment results in a dramatic increase in effector CD8 T cells in the
      prostate gland, and enhanced tumor-antigen directed lytic function. These effects
      are maximized when CTLA-4 blockade is applied after, but not before, vaccination.
      Additional experiments, using models of metastatic disease, show that
      incorporation of low-dose cyclophosphamide into this combined treatment regimen
      results in an additional pre-clinical benefit. CONCLUSIONS: Together these
      studies define a combination regimen using anti-CTLA-4/GVAX immunotherapy and low
      dose chemotherapy for potential translation to a clinical trial setting.

PMID- 23557196
TI  - Discrepancies between tissue Doppler velocities on different echocardiography
      machines: comparing apples to oranges.

PMID- 23557197
TI  - Rapid, scalable and highly automated HLA genotyping using next-generation
      sequencing: a transition from research to diagnostics.
AB  - BACKGROUND: Human leukocyte antigen matching at allelic resolution is proven
      clinically significant in hematopoietic stem cell transplantation, lowering the
      risk of graft-versus-host disease and mortality. However, due to the ever growing
      HLA allele database, tissue typing laboratories face substantial challenges. In
      light of the complexity and the high degree of allelic diversity, it has become
      increasingly difficult to define the classical transplantation antigens at high
      resolution by using well-tried methods. Thus, next-generation sequencing is
      entering into diagnostic laboratories at the perfect time and serving as a
      promising tool to overcome intrinsic HLA typing problems. Therefore, we have
      developed and validated a scalable automated HLA class I and class II typing
      approach suitable for diagnostic use. RESULTS: A validation panel of 173 clinical
      and proficiency testing samples was analysed, demonstrating 100% concordance to
      the reference method. From a total of 1,273 loci we were able to generate 1,241
      (97.3%) initial successful typings. The mean ambiguity reduction for the analysed
      loci was 93.5%. Allele assignment including intronic sequences showed an improved
      resolution (99.2%) of non-expressed HLA alleles. CONCLUSION: We provide a
      powerful HLA typing protocol offering a short turnaround time of only two days, a
      fully integrated workflow and most importantly a high degree of typing
      reliability. The presented automated assay is flexible and can be scaled by
      specific primer compilations and the use of different 454 sequencing systems. The
      workflow was successfully validated according to the policies of the European
      Federation for Immunogenetics. Next-generation sequencing seems to become one of
      the new methods in the field of Histocompatibility.

PMID- 23557195
TI  - SvSXP: a Strongylus vulgaris antigen with potential for prepatent diagnosis.
AB  - BACKGROUND: Strongyle parasites are ubiquitous in grazing horses. Strongylus
      vulgaris, the most pathogenic of the large strongyles, is known for its extensive
      migration in the mesenteric arterial system. The lifecycle of S. vulgaris is
      characterised by a long prepatent period where the migrating larvae are virtually
      undetectable as there currently is no test available for diagnosing prepatent S.
      vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes
      endarteritis and thrombosis with a risk of non-strangulating intestinal
      infarctions. Emergence of anthelmintic resistance among cyathostomins has led to
      recommendations of reduced treatment intensity by targeting horses that exceed a
      predetermined strongyle faecal egg count threshold. One study suggests an
      apparent increase in prevalence of S. vulgaris on farms where reduced
      anthelmintic treatment intensity has been implemented. These issues highlight the
      need for an accurate and reliable assay for diagnosing prepatent S. vulgaris
      infection. METHODS: Immunoscreening of a larval S. vulgaris cDNA library using
      hyperimmune serum raised against S. vulgaris excretory/secretory antigens was
      performed to identify potential diagnostic antigens. Immunoreactive clones were
      sequenced, one potential antigen was characterised, expressed as a recombinant
      protein, initially evaluated by western blot (WB) analysis, the diagnostic
      potential of the IgG subclasses was evaluated by ELISA, and the diagnostic
      accuracy evaluated using serum from 102 horses with known S. vulgaris infection
      status. RESULTS: The clone expressing the potential antigen encoded a S. vulgaris
      SXP/RAL2 homologue. The recombinant protein, rSvSXP, was shown to be a potential
      diagnostic antigen by WB analysis, and a target of serum IgGa, IgG(T) and total
      IgG in naturally infected horses, with IgG(T) antibodies being the most reliable
      indicator of S. vulgaris infection in horses. Evaluation of diagnostic accuracy
      of the ELISA resulted in a sensitivity of 73.3%, a specificity of 81.0%, a
      diagnostic odds ratio of 11.69; a positive likelihood ratio (LR) of 3.85 and a
      negative LR was 0.33. The area under the ROC curve was 0.820. CONCLUSION: IgG(T)
      antibodies to recombinant SvSXP show potential for use as an antigen for
      prepatent diagnosis of migrating stages of S. vulgaris with moderate to good
      diagnostic accuracy.

PMID- 23557198
TI  - Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive
      cytotoxicity in acute myeloid leukemia cells.
AB  - Barasertib, an aurora B inhibitor, terminates cell division, introduces
      polyploidy, and consequently causes apoptosis. In the present study, we evaluated
      the effect of the combination of barasertib and cytarabine (ara-C), a key agent
      for leukemia chemotherapy, on leukemic cells in vitro. Human leukemia HL-60 cells
      and HL-60/ara-C20 cells, a 20-fold ara-C-resistant variant, were used. The 50%
      growth inhibitory concentrations of an active metabolite of barasertib,
      barasertib-hydroxyquinazoline-pyrazol-aniline (Barasertib-HQPA), and ara-C were
      51 nM and 300 nM for HL-60 cells and 70 nM and 5300 nM for HL-60/ara-C20 cells,
      respectively. Barasertib-HQPA induced polyploidy with a subsequent induction of
      sub-G1 phase apoptosis, indicating the M-phase specific cytotoxicity. Cells
      treated with the S-phase specific ara-C accumulated in S phase and subsequently
      died through apoptosis. When HL-60 cells were treated with barasertib-HQPA and
      ara-C in combination, a greater-than-additive apoptosis was induced. This
      enhancement was obtained when the cells were treated with barasertib-HQPA prior
      to ara-C (37.9% sub-G1) or with both concurrently (31.2% sub-G1), but not with
      ara-C prior to barasertib-HQPA (17.8% sub-G1). The combination effects were
      similarly obtained in HL-60/ara-C20 cells with 19.7% sub-G1 for barasertib-HQPA
      >ara-C, 18.4% sub-G1 for both concurrently, and 13.8% sub-G1 for ara-C
      >barasertib-HQPA, and another leukemic U937 cells with 25.4% sub-G1 for
      barasertib-HQPA->ara-C, 28.2% sub-G1 for both concurrently, and 16.0% sub-G1 for
      ara-C->barasertib-HQPA. Barasertib-HQPA inhibited aurora B autophosphorylation
      and histone H3 phosphorylation in all the cell lines. Barasertib-HQPA did not
      inhibit DNA synthesis, allowing ara-C incorporation into DNA for its
      cytotoxicity. Thus, barasertib-HQPA and ara-C provided a greater-than-additive
      cytotoxicity in leukemic cells in vitro.

PMID- 23557199
TI  - Discovery of face-centered-cubic ruthenium nanoparticles: facile size-controlled
      synthesis using the chemical reduction method.
AB  - We report the first discovery of pure face-centered-cubic (fcc) Ru nanoparticles.
      Although the fcc structure does not exist in the bulk Ru phase diagram, fcc Ru
      was obtained at room temperature because of the nanosize effect. We succeeded in
      separately synthesizing uniformly sized nanoparticles of both fcc and hcp Ru
      having diameters of 2-5.5 nm by simple chemical reduction methods with different
      metal precursors. The prepared fcc and hcp nanoparticles were both supported on
      gamma-Al2O3, and their catalytic activities in CO oxidation were investigated and
      found to depend on their structure and size.

PMID- 23557200
TI  - Validation of physical activity monitors in individuals with diabetes: energy
      expenditure estimation by the multisensor SenseWear Armband Pro3 and the step
      counter Omron HJ-720 against indirect calorimetry during walking.
AB  - BACKGROUND: The purpose of this study is to test the agreement between energy
      expenditure estimate of the SenseWear((r)) Armband Pro3 (SWA) (BodyMedia,
      Pittsburgh, PA) and the Omron HJ-720 (Omron Healthcare, Kyoto, Japan) step
      counter with indirect calorimetry (IC) as a gold standard in older individuals
      with type 1 and type 2 diabetes mellitus while walking on a treadmill. SUBJECTS
      AND METHODS: In total, six men (60.3+/-3.1 years old) and 13 women (51.1+/-11.0
      years old) with type 1 or type 2 diabetes mellitus were included in the study.
      Each subject performed three 15-min walking sessions with different combinations
      of speed and incline (3 km/h, 0%; 4 km/h, 0%; 5 km/h, 5%) on a treadmill. Energy
      expenditure (EE) was simultaneously measured by the SWA, Omron, and IC. Mean over
      /underestimation and Pearson's correlation coefficients were used for statistical
      evaluation of the agreement between tested methods and IC. RESULTS: At the speed
      of 3 km/h with 0% incline, mean overestimation of +81.19+/-23.81% was found for
      SWA (r=0.79, P<0.001) and +70.51+/-20.91% for Omron (r=0.77, P<0.001). At the
      speed of 4 km/h and 0% incline, mean overestimation found for SWA was +78.18+/
      33.96% (r=0.63, P<0.01) and +75.77+/-33.36% for Omron (r=0.52, P<0.05). At the
      level of high-intensity exercise at the speed of 5 km/h and 5% incline, mean
      underestimation was -7.88+/-16.86% for SWA (r=0.74, P<0.001) and -7.37+/-16.07%
      for Omron (r=0.75, P<0.001). CONCLUSIONS: Both methods led to considerable
      overestimation of calculated EE in level walking and a relatively minor
      underestimation during fast uphill walking.

PMID- 23557203
TI  - Feeding height stratification among the herbivorous dinosaurs from the Dinosaur
      Park Formation (upper Campanian) of Alberta, Canada.
AB  - BACKGROUND: Herbivore coexistence on the Late Cretaceous island continent of
      Laramidia has been a topic of great interest, stemming from the paradoxically
      high diversity and biomass of these animals in relation to the relatively small
      landmass available to them. Various hypotheses have been advanced to account for
      these facts, of which niche partitioning is among the most frequently invoked.
      However, despite its wide acceptance, this hypothesis has not been rigorously
      tested. This study uses the fossil assemblage from the Dinosaur Park Formation of
      Alberta as a model to investigate whether niche partitioning facilitated
      herbivorous dinosaur coexistence on Laramidia. Specifically, the question of
      feeding height stratification is examined in light of the role it plays in
      facilitating modern ungulate coexistence. RESULTS: Most herbivorous dinosaur
      species from the Dinosaur Park Formation were restricted to feeding no higher
      than approximately 1 m above the ground. There is minimal evidence for feeding
      height partitioning at this level, with ceratopsids capable of feeding slightly
      higher than ankylosaurs, but the ecological significance of this is ambiguous.
      Hadrosaurids were uniquely capable of feeding up to 2 m quadrupedally, or up to 5
      m bipedally. There is no evidence for either feeding height stratification within
      any of these clades, or for change in these ecological relationships through the
      approximately 1.5 Ma record of the Dinosaur Park Formation. CONCLUSIONS: Although
      we cannot reject the possibility, we find no good evidence that feeding height
      stratification, as revealed by reconstructed maximum feeding heights, played an
      important role in facilitating niche partitioning among the herbivorous dinosaurs
      of Laramidia. Most browsing pressure was concentrated in the herb layer, although
      hadrosaurids were capable of reaching shrubs and low-growing trees that were out
      of reach from ceratopsids, ankylosaurs, and other small herbivores, effectively
      dividing the herbivores in terms of relative abundance. Sympatric hadrosaurids
      may have avoided competing with one another by feeding differentially using
      bipedal and quadrupedal postures. These ecological relationships evidently proved
      to be evolutionarily stable because they characterize the herbivore assemblage of
      the Dinosaur Park Formation through time. If niche partitioning served to
      facilitate the rich diversity of these animals, it may have been achieved by
      other means in addition to feeding height stratification. Consideration of other
      feeding height proxies, including dental microwear and skull morphology, may help
      to alleviate problems of underdetermination identified here.

PMID- 23557201
TI  - HIV restriction in quiescent CD4+ T cells.
AB  - The restriction of the Human Immunodeficiency Virus (HIV) infection in quiescent
      CD4+ T cells has been an area of active investigation. Early studies have
      suggested that this T cell subset is refractory to infection by the virus.
      Subsequently it was demonstrated that quiescent cells could be infected at low
      levels; nevertheless these observations supported the earlier assertions of
      debilitating defects in the viral life cycle. This phenomenon raised hopes that
      identification of the block in quiescent cells could lead to the development of
      new therapies against HIV. As limiting levels of raw cellular factors such as
      nucleotides did not account for the block to infection, a number of groups
      pursued the identification of cellular proteins whose presence or absence may
      impact the permissiveness of quiescent T cells to HIV infection. A series of
      studies in the past few years have identified a number of host factors implicated
      in the block to infection. In this review, we will present the progress made,
      other avenues of investigation and the potential impact these studies have in the
      development of more effective therapies against HIV.

PMID- 23557205
TI  - Psoriasis: different clinical phenotypes.

PMID- 23557204
TI  - The correlation of SUVmax with pathological characteristics of primary tumor and
      the value of Tumor/ Lymph node SUVmax ratio for predicting metastasis to lymph
      nodes in resected NSCLC patients.
AB  - BACKGROUND: We aimed to investigate the correlation of maximum standardized
      uptake value (SUVmax) with pathological characteristics of primary tumor and to
      determine a Tumor/ Lymph node (T/LN) SUVmax ratio predicting metastasis to lymph
      nodes in NSCLC patients. METHODS: Eighty-one NSCLC patients who had PET/CT
      examination at initial staging and subsequently underwent surgical resection were
      retrospectively evaluated. There were 100 PET/CT positive mediastinal or hilar
      lymph node stations. Pathological characteristics of the tumor such as largest
      tumor diameter, tumor histology, differentiation, number of mitosis, degree of
      stromal inflammation, necrosis; etiology of PET/CT positive lymph node stations;
      SUVmax of primary tumor and positive lymph node stations were recorded. A T/LN
      SUVmax ratio was calculated for each lymph node station. RESULTS: SUVmax of the
      primary tumor was positively correlated with the largest tumor diameter (p=0.001,
      r=0.374), number of mitosis (p<0.001, r=0.405), and postoperative pathological
      stage (p=0.007, r=0.298). Patients with squamous cell carcinoma had a
      statistically significant higher mean SUVmax, number of mitosis and advanced N
      stages compared to adenocarcinoma. The etiology of 100 PET/CT positive lymph node
      stations were metastasis in 14, anthracosis in 40, reactive in 39, granulomatous
      in 4, and silicosis in 3 patients. A T/LN SUVmax ratio of 5 or lower was
      suggestive for a malignant lymph node with a sensitivity of 92.8% and specificity
      of 47%. CONCLUSIONS: SUVmax of a primary tumor is related to certain pathological
      characteristics, such as largest diameter, histology, and number of mitosis. A
      T/LN SUVmax ratio lower than 5 predicts the metastasis to lymph nodes with a high
      sensitivity.

PMID- 23557206
TI  - N,N-dimethyldodecylamine oxide self-organization in the presence of lanthanide
      ions in aqueous and aqueous-decanol solutions.
AB  - The article represents the results of research in self-organization of new
      lanthanide systems in water-decanol medium. The systems are based on N,N
      dimethyldodecylamine oxide, a zwitterionic surfactant. The study covers the
      complex formation of lanthanide ions with C12DMAO molecules and the influence of
      Ln(III) ions and medium composition on surfactant association in diluted
      solutions. The analysis of adsorption isotherms was carried out on the basis of
      the combination of Gibbs and Langmuir adsorption equations. The results were used
      to determine physicochemical properties and parameters of a monomolecular
      adsorption layer. The research objects were various lanthanide ions with
      identical coordination centers. A number of spectroscopic methods (UV, NMR self
      diffusion, EPR, dynamic light scattering (DLS), and fluorescent analysis) were
      involved in the research for comparative estimations of molecular dynamics,
      critical micellization concentration, geometry, sizes, and aggregation numbers of
      micellar aggregates. Micelle structure simulation revealed good agreement between
      experimental data and quantum chemical calculations.

PMID- 23557207
TI  - Cortical control of tongue protrusion and lateral movements in the cat.
AB  - Based on area P lesion experiments, we hypothesized that tongue protrusion
      adapted for licking might be regulated by the lateral wall of the presylvian
      sulcus (bilateral areas P) of the cerebral cortex (Hiraba H, Sato T, Nakakawa K,
      Ueda K. 2009. Cortical control of appropriate tongue protrusion during licking in
      cats--Increase in regional cerebral blood flow (rCBF) of the contralateral area P
      and in tongue protrusion after the unilateral area P lesion. Somatosens Mot Res
      26:82-89). We propose that the right and left lingual muscles are dominated by
      the right and left hypoglossal nucleus, respectively, and that right and left
      pyramidal cells projecting to the right and left hypoglossal nucleus,
      respectively, exist in unilateral area P. These cells project via an inhibitory
      interneuron relay to the lateral branches toward the left or right pyramidal
      cells in contralateral area P. In this study, we aimed to demonstrate the
      existence of inhibitory interneurons using injections of a gamma-aminobutyric
      acid (GABA) agonist (muscimol), a GABA antagonist (bicuculline), and kainic acid
      into unilateral area P, followed by examination of tongue protrusion and lateral
      movements during trained licking and changes in regional cerebral blood flow
      (rCBF) values in the contralateral area P. We found disordered protrusion toward
      both sides and a marked decrease in rCBF values in the contralateral area P after
      bicuculline injection. We also found abnormal tongue protrusion toward the front
      and a marked increase in rCBF values after muscimol and kainic acid injections.
      These results suggest that cortical networks between the bilateral areas P are
      relayed by inhibitory interneurons.

PMID- 23557208
TI  - Why is CA3 more vulnerable than CA1 in experimental models of controlled cortical
      impact-induced brain injury?
AB  - One interesting finding of controlled cortical impact (CCI) experiments is that
      the CA3 region of the hippocampus, which is positioned further from the impact
      than the CA1 region, is reported as being more injured. The current literature
      has suggested a positive correlation between brain tissue stretch and neuronal
      cell loss. However, it is counterintuitive to assume that CA3 is stretched more
      during CCI injury. Recent mechanical studies of the brain have reported on a
      level of spatial heterogeneity not previously appreciated-the finding that CA1
      was significantly stiffer than all other regions tested and that CA3 was one of
      the most compliant. We hypothesized that mechanical heterogeneity of anatomical
      structures could underlie the proposed heterogeneous mechanical response and
      hence the pattern of cell death. As such, we developed a three-dimensional finite
      element (FE) rat brain model representing detailed hippocampal structures and
      simulated various CCI experiments. Four groups of material properties based on
      recent experiments were tested. In group 1, hyperelastic material properties were
      assigned to various hippocampal structures, with CA3 more compliant than CA1. In
      group 2, linear viscoelastic material properties were assigned to hippocampal
      structures, with CA3 more compliant than CA1. In group 3, the hippocampus was
      represented by homogenous linear viscoelastic material properties. In group 4, a
      homogeneous nonlinear hippocampus was adopted. Simulation results demonstrated
      that for CCI with a 5-mm diameter, flat shape impactor, CA3 experienced increased
      tensile strains over a larger area and to a greater magnitude than did CA1 for
      group 1, which best explained why CA3 is more sensitive to CCI injury. However,
      for groups 2-4, the total volume with high strain (>30%) in CA3 was smaller than
      that in CA1. The FE rat brain model, with detailed hippocampal structures
      presented here, will help to engineer desired experimental neurotrauma models by
      virtually characterizing brain biomechanics before testing.

PMID- 23557209
TI  - Radiosynthesis and preclinical evaluation of [11C]prucalopride as a potential
      agonist PET ligand for the 5-HT4 receptor.
AB  - BACKGROUND: Serotonin 5-HT4 receptor (5-HT4-R) agonists are potential therapeutic
      agents for enterokinetic and cognitive disorders and are marketed for treatment
      of constipation. The aim of this study was to develop an agonist positron
      emission tomography (PET) ligand in order to label the active G-protein coupled 5
      HT4-R in peripheral and central tissues. For this purpose prucalopride, a high
      affinity selective 5-HT4-R agonist, was selected. METHODS: [11C]Prucalopride was
      synthesized from [11C]methyl triflate and desmethyl prucalopride, and its
      LogDoct,pH7.4 was determined. Three distinct studies were performed with
      administration of IV [11C]prucalopride in male rats: (1) The biodistribution of
      radioactivity was measured ex vivo; (2) the kinetics of radioactivity levels in
      brain regions and peripheral organs was assessed in vivo under baseline
      conditions and following pre-treatment with tariquidar, a P-glycoprotein efflux
      pump inhibitor; and (3) in vivo stability of [11C]prucalopride was checked ex
      vivo in plasma and brain extracts using high-performance liquid chromatography.
      RESULTS: [11C]Prucalopride was synthesized in optimised conditions with a yield
      of 21% +/- 4% (decay corrected) and a radiochemical purity (>99%), its
      LogDoct,pH7.4 was 0.87. Ex vivo biodistribution studies with [11C]prucalopride in
      rats showed very low levels of radioactivity in brain (maximal 0.13% ID.g-1) and
      ten times higher levels in certain peripheral tissues. The PET studies confirmed
      very low brain levels of radioactivity under baseline conditions; however, it was
      increased three times after pre-treatment with tariquidar. [11C]Prucalopride was
      found to be very rapidly metabolised in rats, with no parent compound detectable
      in plasma and brain extracts at 5 and 30 min following IV administration.
      Analysis of levels of radioactivity in peripheral tissues revealed a distinct PET
      signal in the caecum, which was reduced following tariquidar pre-treatment. The
      latter is in line with the role of the P-glycoprotein pump in the gut.
      CONCLUSION: [11C]Prucalopride demonstrated low radioactivity levels in rat brain;
      a combination of reasons may include rapid metabolism in the rat in particular,
      low passive diffusion and potential P-glycoprotein substrate. In humans, further
      investigation of [11C]prucalopride for imaging the active state of 5-HT4-R is
      worthwhile, in view of the therapeutic applications of 5-HT4 agonists for
      treatment of gastrointestinal motility disorders.

PMID- 23557210
TI  - Au(I)/Ag(I)-catalyzed cascade approach for the synthesis of benzo[4,5]imidazo[1,2
      c]pyrrolo[1,2-a]quinazolinones.
AB  - An efficient and facile Au(I)/Ag(I)-catalyzed cascade method has been developed
      for one-pot synthesis of the complex polycyclic heterocycles
      benzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazolinone derivatives through treatment
      of the substituted 2-(1H-benzo[d]imidazol-2-yl)anilines with 4-pentynoic acid or
      5-hexynoic acid. The strategy features a Au(I)/Ag(I)-catalyzed one-pot cascade
      process involving the formation of three new C-N bonds in high yields, and with
      broad a substrate scope.

PMID- 23557211
TI  - Response to Zizzo et al.

PMID- 23557213
TI  - Sex differences in trajectories of depressive symptoms among older Taiwanese: the
      contribution of selected stressors and social factors.
AB  - OBJECTIVES: We assessed female-male differences in depressive symptoms among
      older Taiwanese and quantified the contribution of sex differences in exposure
      and response to selected covariates in explaining the gap. METHODS: Using data
      from six survey waves over 18 years for a nationally representative cohort of
      4049 Taiwanese aged 60+, we employed growth curve analysis to model individual
      level trajectories of depressive symptoms across age. RESULTS: Among older
      Taiwanese, women's disadvantage with respect to social position and employment
      accounted for about 40% of the sex difference in depressive symptoms. Sex
      differences in decision control and exposure to widowhood and financial decline
      played surprisingly little role. Although we found no evidence that the effects
      of marriage, recent widowhood or recent child death varied by sex, living apart
      from one's children appeared to be more detrimental for women than for men in
      this society. Moreover, the effect of living with children depended on the
      arrangement: living with an unmarried son was more strongly associated with
      depressive symptoms than living with a married son and daughter-in-law.
      CONCLUSION: Sex differentials in social position and employment are major
      contributors to the sex difference in depressive symptoms among older Taiwanese,
      yet sex differences in exposure or response to selected stressors appear to play
      little role. Differential vulnerabilities to particular living arrangements may
      also contribute to women's excess psychological distress, although more research
      is needed to elucidate the mechanisms by which living arrangements influence
      depressive symptoms in Taiwan.

PMID- 23557214
TI  - Relations between aggression and adjustment in chinese children: moderating
      effects of academic achievement.
AB  - The primary purpose of the study was to examine the moderating effects of
      academic achievement on relations between aggressive behavior and social and
      psychological adjustment in Chinese children. A sample of children (N = 1,171;
      591 boys, 580 girls; initial M age = 9 years) in China participated in the study.
      Two waves of longitudinal data were collected in Grades 3 and 4 from multiple
      sources including peer nominations, teacher ratings, self-reports, and school
      records. The results indicated that the main effects of aggression on adjustment
      were more evident than those of adjustment on aggression. Moreover, aggression
      was negatively associated with later leadership status and positively associated
      with later peer victimization, mainly for high-achieving children. The results
      suggested that consistent with the resource-potentiating model, academic
      achievement served to enhance the positive development of children with low
      aggression. On the other hand, although the findings indicated fewer main effects
      of adjustment on aggression, loneliness, depression, and perceived social
      incompetence positively predicted later aggression for low-achieving, but not
      high-achieving, children, which suggested that consistent with the stress
      buffering model, academic achievement protected children with psychological
      difficulties from developing aggressive behavior. The results indicate that
      academic achievement is involved in behavioral and socioemotional development in
      different manners in Chinese children. Researchers should consider an integrative
      approach based on children's behavioral, psychological, and academic functions in
      designing prevention and intervention programs. 

PMID- 23557215
TI  - Medicare payment reform and provider entry and exit in the post-acute care
      market.
AB  - OBJECTIVE: To understand the impacts of Medicare payment reform on the entry and
      exit of post-acute providers. DATA SOURCES: Medicare Provider of Services data,
      Cost Reports, and Census data from 1991 through 2010. STUDY DESIGN: We examined
      market-level changes in entry and exit after payment reforms relative to a
      preexisting time trend. We also compared changes in high Medicare share markets
      relative to lower Medicare share markets and for freestanding relative to
      hospital-based facilities. DATA EXTRACTION METHODS: We calculated market-level
      entry, exit, and total stock of home health agencies, skilled nursing facilities,
      and inpatient rehabilitation facilities from Provider of Services files between
      1992 and 2010. We linked these measures with demographic information from the
      Census and American Community Survey, information on Certificate of Need laws,
      and Medicare share of facilities in each market drawn from Cost Report data.
      PRINCIPAL FINDINGS: Payment reforms reducing average and marginal payments
      reduced entries and increased exits from the market. Entry effects were larger
      and more persistent than exit effects. Entry and exit rates fluctuated more for
      home health agencies than skilled nursing facilities. Effects on number of
      providers were consistent with entry and exit effects. CONCLUSIONS: Payment
      reform affects market entry and exit, which in turn may affect market structure,
      access to care, quality and cost of care, and patient outcomes. Policy makers
      should consider potential impacts of payment reforms on post-acute care market
      structure when implementing these reforms.

PMID- 23557216
TI  - SOX7 is down-regulated in lung cancer.
AB  - BACKGROUND: SOX7 is a transcription factor belonging to the SOX family. Its role
      in lung cancer is unknown. METHODS: In this study, whole genomic copy number
      analysis was performed on a series of non-small cell lung cancer (NSCLC) cell
      lines and samples from individuals with epidermal growth factor receptor (EGFR)
      mutations using a SNP-Chip platform. SOX7 was measured in NSCLC samples and cell
      lines, and forced expressed in one of these lines. RESULTS: A notable surprise
      was that the numerous copy number (CN) changes observed in samples of Asian, non
      smoking EGFR mutant NSCLC were nearly the same as those CN alterations seen in a
      large collection of NSCLC from The Cancer Genome Atlas which is presumably
      composed of predominantly Caucasians who often smoked. However, four regions had
      CN changes fairly unique to the Asian EGFR mutant group. We also examined CN
      changes in NSCLC lines. The SOX7 gene was homozygously deleted in one (HCC2935)
      of 10 NSCLC cell lines and heterozygously deleted in two other NSCLC lines.
      Expression of SOX7 was significantly downregulated in NSCLC cell lines (8/10,
      80%) and a large collection of NSCLC samples compared to matched normal lung
      (57/62, 92%, p= 0.0006). Forced-expression of SOX7 in NSCLC cell lines markedly
      reduced their cell growth and enhanced their apoptosis. CONCLUSION: These data
      suggest that SOX7 is a novel tumor suppressor gene silenced in the majority of
      NSCLC samples.

PMID- 23557217
TI  - Radiation mitigating properties of the lignan component in flaxseed.
AB  - BACKGROUND: Wholegrain flaxseed (FS), and its lignan component (FLC) consisting
      mainly of secoisolariciresinol diglucoside (SDG), have potent lung
      radioprotective properties while not abrogating the efficacy of radiotherapy.
      However, while the whole grain was recently shown to also have potent mitigating
      properties in a thoracic radiation pneumonopathy model, the bioactive component
      in the grain responsible for the mitigation of lung damage was never identified.
      Lungs may be exposed to radiation therapeutically for thoracic malignancies or
      incidentally following detonation of a radiological dispersion device. This could
      potentially lead to pulmonary inflammation, oxidative tissue injury, and
      fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in
      a mouse model of radiation pneumonopathy. METHODS: We evaluated FLC-supplemented
      diets containing SDG lignan levels comparable to those in 10% and 20% whole grain
      diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC)
      were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after
      single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4
      months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and
      oxidative damage levels, and survival. RESULTS: FLC significantly mitigated
      radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7%
      survival 4 months post-XRT compared to 60-73.3% survival in mice fed 10%-20% FLC
      initiated 24-72 hours post-XRT. FLC also mitigated radiation-induced lung
      fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased
      fibrosis as compared to mice fed control diet while the corresponding TGF-beta1
      levels detected immunohistochemically were also decreased. Additionally, 10-20%
      FLC initiated at any time point post radiation exposure, mitigated radiation
      induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein
      and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly,
      neutrophilic and overall inflammatory cell infiltrate in airways and levels of
      nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively)
      were also mitigated by the lignan diet. CONCLUSIONS: Dietary FLC given early post
      XRT mitigated radiation effects by decreasing inflammation, lung injury and
      eventual fibrosis while improving survival. FLC may be a useful agent, mitigating
      adverse effects of radiation in individuals exposed to incidental radiation,
      inhaled radioisotopes or even after the initiation of radiation therapy to treat
      malignancy.

PMID- 23557219
TI  - Screening for ectasia risk: what are we screening for and how should we screen
      for it?

PMID- 23557218
TI  - High EGFR copy number predicts benefits from tyrosine kinase inhibitor treatment
      for non-small cell lung cancer patients with wild-type EGFR.
AB  - BACKGROUND: This study was designed to determine whether advanced non-small-cell
      lung cancer (NSCLC) patients with high copy number of epidermal growth factor
      receptor (EGFR) can benefit from treatment with EGFR-tyrosine kinase inhibitors
      (TKIs). METHODS: EGFR gene copy number was assessed by fluorescence in situ
      hybridization (FISH) and EGFR mutations was tested using Luminex xTAG technology
      in 502 TKI-treated NSCLC patients. The association between both biomarkers and
      clinical benefit from EGFR-TKI were analyzed. RESULTS: EGFR FISH+and EGFR
      mutations were significantly associated with higher response rates (37.2% and
      43.7%, respectively), superior progression-free survival (PFS) (FISH+, 11.2
      months; hazard ratio [HR], 0.51; 95% CI, 0.42 to 0.62; p<0.001; mutation+, 11.7
      months; HR, 0.37; 95% CI, 0.31 to 0.45; p<0.001) and overall survival (OS)
      (FISH+, 30.2 months; HR, 0.51; 95% CI, 0.40 to 0.65; p<0.001; mutation+, 30.2
      months; HR, 0.45; 95% CI, 0.36 to 0.58; p<0.001). In patients with wild-type
      EGFR, EGFR FISH+correlated with longer PFS than EGFR FISH- status (4.4 months vs.
      2.0 months; HR, 0.56; 95% CI, 0.41 to 0.75; p<0.001), so did amplification (5.0
      months vs. 2.0 months; HR, 0.43; 95% CI, 0.24 to 0.76; p=0.003). However,
      FISH+had no association with improved PFS in EGFR-mutated patients (HR, 0.77; 95%
      CI, 0.57 to 1.03; p=0.076). CONCLUSIONS: A combined analysis of EGFR FISH and
      mutation is an effective predictor of EGFR-TKI therapy. Specifically, a high EGFR
      copy number may predict benefit from TKIs treatment for NSCLC patients with wild
      type EGFR.

PMID- 23557221
TI  - Comparison of four different VisuMax circle patterns for flap creation after
      small incision lenticule extraction.
AB  - PURPOSE: To compare four different Circle patterns for flap creation after small
      incision lenticule extraction (SMILE). METHODS: SMILE was performed on six
      rabbits. Twenty-eight days after the initial procedure, corneal flaps were
      created using Circle patterns. Rabbits were divided into four groups (patterns A,
      B, C, and D). Pattern A creates a circular side cut to meet the cap cut within
      the clearance zone (outside of the optical zone). Patterns B, C, and D create a
      lamellar ring posterior, anterior, and at the same depth, respectively, to the
      cap to meet the cap cut in the clearance zone with the help of a junction cut.
      Difficulty of flap lift was graded from 1 (easiest) to 5 (most difficult). The
      bed quality was assessed by scanning electron microscopy. RESULTS: Flaps created
      by patterns A and D were the easiest to lift (grade 2). The resulting flap bed
      was smooth and undisrupted. However, pattern A resulted in a reduced re-treatment
      area. Flaps created by pattern B were the most difficult to lift (grade 4). The
      stromal dissection was difficult in an attempt to ascertain the original optical
      zone from the lamellar ring, placed posterior. Flaps produced by pattern C were
      easy to lift, with minor intrastromal resistance experienced during the lifting
      process (grade 3). The transition between the lamellar ring and cap cut was
      hardly discernible in pattern C-treated corneas. CONCLUSIONS: Pattern D, a
      lamellar ring adjacent to the cap cut, was the most optimal to be used for flap
      creation in cases of SMILE re-treatment.

PMID- 23557222
TI  - Binocularity enhances visual acuity of eyes implanted with multifocal intraocular
      lenses.
AB  - PURPOSE: To investigate the effect of binocularity on long-term visual acuity in
      patients who have undergone bilateral implantation of a presbyopia-correcting
      diffractive multifocal intraocular lens (IOL). METHODS: Twenty patients (9 men
      and 11 women) with an average age of 70 +/- 7 years (range: 56 to 78 years)
      underwent bilateral implantation of a diffractive multifocal IOL (AcrySof IQ
      ReSTOR IOL, SN60D3; Alcon Laboratories, Inc., Fort Worth, TX). Uncorrected visual
      acuity was measured monocularly and binocularly on average 26 +/- 6 months
      following implantation in the second eye (range: 17 to 40 months) using the
      University of Crete European-wide modified Early Treatment Diabetic Retinopathy
      Study charts at the following distances: (1) 4 m, uncorrected distance visual
      acuity (UDVA), (2) 66 cm, uncorrected intermediate visual acuity (UIVA), and (3)
      33 cm, uncorrected near visual (UNVA). RESULTS: Mean +/- standard deviation UDVA
      was 0.07 +/- 0.10 and 0.21 +/- 0.12 logMAR (20/23 and 20/32 Snellen) in the
      better and worse eye, respectively, improving to 0.00 +/- 0.09 logMAR (20/20
      Snellen) binocularly. Mean +/- standard deviation UIVA was 0.18 +/- 0.14 and 0.32
      +/- 0.15 logMAR (20/30 and 20/42 Snellen) in the better and worse eye,
      respectively, improving to 0.08 +/- 0.15 logMAR (20/24 Snellen) binocularly. Mean
      +/- standard deviation UNVA was 0.20 +/- 0.09 and 0.32 +/- 0.12 logMAR (20/32 and
      20/42 Snellen) in the better and worse eye, respectively, improving to 0.11 +/-
      0.10 logMAR (20/26 Snellen) binocularly. Binocular summation, defined as the
      difference between the binocular and better eye visual acuity, was found to be
      statistically significant at all distances: 0.07 +/- 0.05 logMAR at 4 m, 0.10 +/-
      0.11 logMAR at 66 cm, and 0.09 +/- 0.08 logMAR at 33 cm. CONCLUSIONS: The results
      confirm that there is substantial benefit of binocular vision in individuals with
      bilateral multifocal IOL implantation in terms of increased visual acuity. This
      effect is evident at all distances.

PMID- 23557223
TI  - Clinical and optical intraocular performance of rotationally asymmetric
      multifocal IOL plate-haptic design versus C-loop haptic design.
AB  - PURPOSE: To compare the visual and intraocular optical quality outcomes with
      different designs of the refractive rotationally asymmetric multifocal
      intraocular lens (MFIOL) (Lentis Mplus; Oculentis GmbH, Berlin, Germany) with or
      without capsular tension ring (CTR) implantation. METHODS: One hundred thirty
      five consecutive eyes of 78 patients with cataract (ages 36 to 82 years) were
      divided into three groups: 43 eyes implanted with the C-Loop haptic design
      without CTR (C-Loop haptic only group); 47 eyes implanted with the C-Loop haptic
      design with CTR (C-Loop haptic with CTR group); and 45 eyes implanted with the
      plate-haptic design (plate-haptic group). Visual acuity, contrast sensitivity,
      defocus curve, and ocular and intraocular optical quality were evaluated at 3
      months postoperatively. RESULTS: Significant differences in the postoperative
      sphere were found (P = .01), with a more myopic postoperative refraction for the
      C-Loop haptic only group. No significant differences were detected in photopic
      and scotopic contrast sensitivity among groups (P ? .05). Significantly better
      visual acuities were present in the C-Loop haptic with CTR group for the defocus
      levels of -2.0, -1.5, -1.0, and -0.50 D (P ?.03). Statistically significant
      differences among groups were found in total intraocular root mean square (RMS),
      high-order intraocular RMS, and intraocular coma-like RMS aberrations (P ?.04),
      with lower values from the plate-haptic group. CONCLUSIONS: The plate-haptic
      design and the C-Loop haptic design with CTR implantation both allow good visual
      rehabilitation. However, better refractive predictability and intraocular optical
      quality was obtained with the plate-haptic design without CTR implantation. The
      plate-haptic design seems to be a better design to support rotational asymmetric
      MFIOL optics.

PMID- 23557224
TI  - The effects of mitomycin C on tear function after photorefractive keratectomy: a
      contralateral comparative study.
AB  - PURPOSE: To assess the effects of adjuvant mitomycin C (MMC) on tear function
      tests after photorefractive keratectomy (PRK) for myopia. METHODS: In this
      prospective, randomized, double-blind study, one eye of myopic patients
      undergoing PRK was randomly chosen for PRK and the other eye was treated with PRK
      plus the application of 0.02% MMC for 20 seconds onto the ablated stroma. All
      patients had corneal esthesiometry, fluorescein break-up time testing,
      fluorescein and Rose Bengal staining, and Schirmer testing with anesthesia, and
      they also completed a questionnaire preoperatively and at 1.5, 3, 6, and 12
      months after surgery. RESULTS: Twenty-seven patients with a mean age of 25 +/-
      3.27 years were enrolled. There were no statistically significant differences
      between the PRK and PRK+MMC groups regarding the symptoms and tear function tests
      preoperatively or at any postoperative follow-up visit. Preoperative and
      postoperative results in the total sample were also compared; statistically
      significantly different results were observed in fluorescein break-up time and
      dry eye symptoms at 1.5 months, which showed improvement thereafter. Corneal
      sensation was significantly lower at all postoperative follow-up visits compared
      with preoperative results. CONCLUSIONS: The intraoperative use of MMC during PRK
      did not induce tear deficiency, and it seems that MMC can be used safely when
      necessary.

PMID- 23557225
TI  - Inferior intrastromal corneal ring segments in paracentral keratoconus with no
      coincident topographic and coma axis.
AB  - PURPOSE: To assess the visual and refractive outcomes of implantation of
      intrastromal corneal ring segments (ICRS) in keratoconic eyes with no coincident
      topographic and comatic axes. METHODS: Forty-one keratoconic eyes of 39 patients
      with no coincident topographic and comatic axes were implanted inferiorly with a
      Ferrara-type ICRS (Keraring SI6; Mediphacos Inc., Belo Horizonte, Brazil) of 150
      degrees  of arc with a thickness of 150, 200, and 250 MUm. Uncorrected distance
      visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal coma-like
      root mean square, and residual refractive errors analyzed using vector analysis
      were recorded before and 6 months after the ICRS implantation. RESULTS: Mean UDVA
      was 0.76 +/- 0.41 logMAR before and 0.53 +/- 0.46 logMAR after surgery (P =
      .0006). CDVA was 0.13 +/- 0.14 logMAR before and 0.07 +/- 0.09 logMAR after
      surgery (P = .0007). Two eyes (4.9%) lost two lines or more of CDVA, 3 eyes
      (7.32%) lost one line, 16 eyes (39.02%) had no change in CDVA, 9 eyes (21.95%)
      gained one line, and 11 eyes (26.83%) gained two lines or more of CDVA. The
      safety index was 1.10. Spherical equivalent was significantly reduced after ICRS
      implantation (P < .001). Corneal coma-like root mean square changed from 0.80 +/-
      0.53 MUm before surgery to 0.61 +/- 0.59 MUm after surgery (P = .02) for 4.5 mm
      of pupil size. CONCLUSIONS: One Ferrara-type ICRS of 150 degrees  of arc with a
      thickness of 150, 200, or 250 MUm implanted inferiorly may reduce both
      astigmatism and corneal coma-like aberrations in keratoconic eyes with no
      coincident topographic and comatic axes, providing an improvement of UDVA and
      CDVA values.

PMID- 23557226
TI  - Influence of the reference surface shape for discriminating between normal
      corneas, subclinical keratoconus, and keratoconus.
AB  - PURPOSE: To compare the discriminating ability of corneal elevation generated by
      a dual Scheimpflug analyzer calculated with different reference surfaces for
      distinguishing normal corneas from those with keratoconus and subclinical
      keratoconus. METHODS: A total of 391 eyes of 208 patients were prospectively
      enrolled in the study and divided into three groups: 167 eyes of 113 patients
      with keratoconus, 47 contralateral topographically normal eyes of patients with
      clinically evident keratoconus in the fellow eye, and 177 eyes of 95 refractive
      surgery candidates with normal corneas. All eyes were measured with a dual
      Scheimpflug analyzer (GALILEI Analyzer; Ziemer Ophthalmic Systems AG, Port,
      Switzerland). Maximum elevation values were recorded within the central 5-mm
      diameter in both anterior and posterior elevation maps. Discriminating ability of
      corneal elevation measurements obtained by best-fit toric and aspheric (BFTA) and
      best-fit sphere (BFS) reference surfaces were compared by receiver operator
      characteristic (ROC) curves. RESULTS: ROC curve analysis showed that corneal
      elevation measured by BFTA had a significantly better ability than with BFS for
      distinguishing normal corneas from those with keratoconus and forme fruste
      keratoconus (P = .01). Posterior elevation measured by BFTA had a significantly
      higher predictive accuracy for forme fruste keratoconus than anterior elevation
      with an area under ROC curves of 0.88 and 0.80, respectively (P = .01). The
      sensitivity and specificity achieved with the maximum posterior elevation for
      detecting keratoconus and forme fruste keratoconus were 99% and 99% for
      keratoconus and 82% and 80% for forme fruste keratoconus with the cut-off value
      at 16 and 13 MUm, respectively. CONCLUSIONS: The ability to discriminate between
      normal cornea and forme fruste keratoconus with elevation parameters was
      significantly improved by using BFTA instead of BFS reference surface.

PMID- 23557227
TI  - Biomechanical and refractive behaviors of keratoconic cornea based on three
      dimensional anisotropic hyperelastic models.
AB  - PURPOSE: To investigate the biomechanical and refractive behaviors of normal and
      keratoconic corneas based on three-dimensional anisotropic hyperelastic corneal
      models with two layers. METHODS: Based on an anisotropic hyperelastic formula,
      the finite element method was employed to develop normal and keratoconic corneal
      models in which the fiber orientations and the biomechanical differences between
      corneal layers were taken into account. The displacements for normal and
      keratoconic corneal models were studied, as well as changes in corneal refractive
      power with intraocular pressure (IOP). RESULTS: There were different
      displacements for keratoconic and normal corneas. Positive correlations were
      found in the keratoconic cornea between IOP and apical displacement, as well as
      between IOP and corneal refractive power. Under normal IOP, both the corneal
      shape and refractive power map were affected by the stiffness distributions of
      the corneal layers. CONCLUSIONS: Finite element analysis can be used to
      demonstrate the biomechanical and refractive behavior of a cornea with
      keratoconus. From a biomechanical viewpoint, the displacement changes seen under
      normal IOP were due to the decreased stiffness in the keratoconic corneal tissue
      and local thinning disorders. Thus, the curvature and corneal refractive power
      map will be abnormal in keratoconus.

PMID- 23557228
TI  - Unilateral ectasia after LASIK in a patient with abnormal topography but normal
      tomography.
AB  - PURPOSE: To report a case of unilateral ectasia developing after LASIK in a
      patient with abnormal topography but normal tomographic indices. METHODS: Case
      report and literature review. RESULTS: A patient was treated bilaterally for
      myopia using LASIK. Five years and 5 months postoperatively, unilateral ectasia
      in the right eye was diagnosed. Preoperatively, anterior curvature (Placido) map
      of the right cornea showed an asymmetry with 1.8 diopters of steepening when
      evaluated from upper left to lower right meridians, and a skewing of the steepest
      radial axes. The calculated KISA% index was 128.4 in the right eye and 5.6 in the
      left eye. Conversely, posterior elevation map and pachymetry map of the right eye
      showed no frank abnormalities. CONCLUSIONS: This case is interesting because it
      shows that for this patient, the anterior curvature (Placido) map was more
      sensitive to detect cornea at risk of post-LASIK ectasia than the tomographic
      features

PMID- 23557229
TI  - Fast diastolic swinging motion of the mitral valve as a clinical marker of
      familial hypertrophic cardiomyopathy in genetically affected young children
      without left ventricular hypertrophy: a new role for noninvasive imaging?
AB  - Structural mitral valve (MV) abnormalities are common in patients with
      hypertrophic cardiomyopathy (HCM). This is the first report demonstrating MV
      abnormalities in very young children as the sole overt clinical feature of a
      known HCM-causing sarcomere protein gene mutation. Due to MV leaflet elongation,
      we also noticed a typical fast diastolic swinging motion of the MV in our
      patients. This novel echocardiographic feature may be used as a clinical marker
      of HCM disease in the absence of left ventricular hypertrophy. 

PMID- 23557230
TI  - Determination of specific binding interactions at L-cystine crystal surfaces with
      chemical force microscopy.
AB  - The pathogenesis of L-cystine kidney stones involves four critical steps:
      nucleation, crystal growth, crystal aggregation, and crystal adhesion to cells.
      Although inhibition of crystal growth by L-cystine "imposters" at L-cystine
      crystal surfaces has been suggested as a plausible route for the suppression of
      stones, understanding the factors that govern crystal-crystal aggregation and
      adhesion of crystals to epithelial cells also is essential for devising
      strategies to mitigate L-cystine stone formation. Chemical force microscopy
      performed with atomic force microscope tips decorated with functional groups
      commonly found in urinary constituents that likely mediate aggregation and
      attachment (e.g., COOH, NH2, SH, CH3, OH) revealed signatures that reflect
      differences in the chemical affinity of these groups for the (001) and {100}
      faces of the naturally occurring hexagonal form of L-cystine single crystals and
      the {110} faces of the non-native tetragonal form. These signatures can be
      explained by the different chemical compositions of the crystal faces, and they
      reveal a remarkable binding specificity of the thiol group for the sulfur-rich
      {100} and {110} faces of the hexagonal and tetragonal forms, respectively.
      Collectively, these observations suggest that alterations of the crystal habit
      and polymorph by crystal growth inhibitors may not affect crystal aggregation or
      adhesion to cells significantly.

PMID- 23557231
TI  - Integration of mate pair sequences to improve shotgun assemblies of flow-sorted
      chromosome arms of hexaploid wheat.
AB  - BACKGROUND: The assembly of the bread wheat genome sequence is challenging due to
      allohexaploidy and extreme repeat content (>80%). Isolation of single chromosome
      arms by flow sorting can be used to overcome the polyploidy problem, but the
      repeat content cause extreme assembly fragmentation even at a single chromosome
      level. Long jump paired sequencing data (mate pairs) can help reduce assembly
      fragmentation by joining multiple contigs into single scaffolds. The aim of this
      work was to assess how mate pair data generated from multiple displacement
      amplified DNA of flow-sorted chromosomes affect assembly fragmentation of shotgun
      assemblies of the wheat chromosomes. RESULTS: Three mate pair (MP) libraries (2
      Kb, 3 Kb, and 5 Kb) were sequenced to a total coverage of 89x and 64x for the
      short and long arm of chromosome 7B, respectively. Scaffolding using SSPACE
      improved the 7B assembly contiguity and decreased gene space fragmentation, but
      the degree of improvement was greatly affected by scaffolding stringency applied.
      At the lowest stringency the assembly N50 increased by ~7 fold, while at the
      highest stringency N50 was only increased by ~1.5 fold. Furthermore, a strong
      positive correlation between estimated scaffold reliability and scaffold assembly
      stringency was observed. A 7BS scaffold assembly with reduced MP coverage proved
      that assembly contiguity was affected only to a small degree down to ~50% of the
      original coverage. CONCLUSION: The effect of MP data integration into pair end
      shotgun assemblies of wheat chromosome was moderate; possibly due to poor contig
      assembly contiguity, the extreme repeat content of wheat, and the use of
      amplified chromosomal DNA for MP library construction.

PMID- 23557232
TI  - Portrait of replication stress viewed from telomeres.
AB  - Genetic instability is the driving force of the malignant progression of cancer
      cells. Recently, replication stress has attracted much attention as a source of
      genetic instability that gives rise to an accumulation of mutations during the
      lifespan of individuals. However, the molecular details of the process are not
      fully understood. Here, recent progress in understanding how genetic alterations
      accumulate at telomeres will be reviewed. In particular, two aspects of telomere
      replication will be discussed in this context, covering conventional semi
      conservative replication, and DNA synthesis by telomerase plus the C-strand fill
      in reactions. Although these processes are seemingly telomere-specific, I will
      emphasize the possibility that the molecular understanding of the telomere events
      may shed light on genetic instability at other genetic loci in general. 

PMID- 23557233
TI  - Antigenotoxic properties of chlorophyll b against cisplatin-induced DNA damage
      and its relationship with distribution of platinum and magnesium in vivo.
AB  - The chemotherapeutic agent cisplatin (cDDP) is widely used to treat a variety of
      solid and hematological tumors. However, cDDP exerts severe side effects, such as
      nephrotoxicity, neurotoxicity, and bone-marrow suppression. The use of some
      dietary compounds to protect organs that are not targets in association with
      chemotherapy has been encouraged. This study evaluated the protective effects of
      chlorophyll b (CLb) on DNA damage induced by cDDP by use of single-cell gel
      electrophoresis (SCGE) assays. Further, this investigation also determined
      platinum (Pt) and magnesium (Mg) bioaccumulation in mice tissues after treatment
      with CLb alone and/or in association of cDDP (simultaneous treatment) by
      inductively coupled plasma-mass spectroscopy (ICP-MS). All parameters were
      studied in peripheral blood cells (PBC), kidneys, and liver of mice after
      administration of CLb (0.2 or 0.5 mg/kg of body weight [b.w.]), cDDP (6 mg/kg
      b.w.), and the combination CLb 0.2 plus cDDP or CLb 0.5 plus cDDP. Pt
      accumulation in liver and kidneys was higher than that found in PBC, while DNA
      damage was higher in kidneys and liver than in PBC. Further, treatment with CLb
      alone did not induce DNA damage. Evidence indicates that genotoxic effects
      produced by cDDP may not be related to Pt accumulation and distribution. In
      combined treatments, CLb decreased DNA damage in tissues, but the PT contents did
      not change and these treatments also showed that CLb may be an important source
      of Mg. Thus, our results indicate that consumption of CLb-rich foods may diminish
      the adverse health effects induced by cDDP exposure.

PMID- 23557234
TI  - In vitro assessment of the cytotoxic, apoptotic, and mutagenic potentials of
      isatin.
AB  - Isatin (1H-indole-2,3-dione) is a chemical found in various medicinal plant
      species and responsible for a broad spectrum of pharmacological and biological
      properties that may be beneficial to human health, as an anticonvulsant,
      antibacterial, antifungal, antiviral, and anticancer agent. The aim of the
      present study was to determine in vitro the cytotoxic, mutagenic, and apoptotic
      effects of isatin on CHO-K1 and HeLa cells using the MTT viability assay (3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide), micronucleus (MN) test,
      apoptosis index, and nuclear division index (NDI). The 5 isatin concentrations
      evaluated in the mutagenicity and apoptosis tests were 0.5, 1, 5, 10, and 50 MUM,
      selected through a preliminary MTT assay. Positive (doxorubicin, DXR) and
      negative (phosphate buffered saline, PBS) control groups were also included in
      the analysis. Isatin did not exert a mutagenic effect on CHO-K1 after 3 and 24 h
      of treatment or on HeLa cells after 24 h. However, 10 and 50 MUM concentrations
      inhibited cell proliferation and promoted apoptosis in both CHO-K1 and HeLa
      cells. Data indicate that the cytotoxic, apoptotic, and antiproliferative effects
      of isatin were concentration independent and cell line independent.

PMID- 23557235
TI  - Autoantibodies to nervous system-specific proteins are elevated in sera of flight
      crew members: biomarkers for nervous system injury.
AB  - This descriptive study reports the results of assays performed to detect
      circulating autoantibodies in a panel of 7 proteins associated with the nervous
      system (NS) in sera of 12 healthy controls and a group of 34 flight crew members
      including both pilots and attendants who experienced adverse effects after
      exposure to air emissions sourced to the ventilation system in their aircrafts
      and subsequently sought medical attention. The proteins selected represent
      various types of proteins present in nerve cells that are affected by neuronal
      degeneration. In the sera samples from flight crew members and healthy controls,
      immunoglobin (IgG) was measured using Western blotting against neurofilament
      triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau),
      microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial
      fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation
      in levels of circulating IgG-class autoantibodies in flight crew members was
      found. A symptom-free pilot was sampled before symptoms and then again afterward.
      This pilot developed clinical problems after flying for 45 h in 10 d. Significant
      increases in autoantibodies were noted to most of the tested proteins in the
      serum of this pilot after exposure to air emissions. The levels of autoantibodies
      rose with worsening of his condition compared to the serum sample collected prior
      to exposure. After cessation of flying for a year, this pilot's clinical
      condition improved, and eventually he recovered and his serum autoantibodies
      against nervous system proteins decreased. The case study with this pilot
      demonstrates a temporal relationship between exposure to air emissions, clinical
      condition, and level of serum autoantibodies to nervous system-specific proteins.
      Overall, these results suggest the possible development of neuronal injury and
      gliosis in flight crew members anecdotally exposed to cabin air emissions
      containing organophosphates. Thus, increased circulating serum autoantibodies
      resulting from neuronal damage may be used as biomarkers for chemical-induced CNS
      injury.

PMID- 23557236
TI  - Evaluation of the mutagenicity and genotoxicity of Arrabidaea chica Verlot
      (Bignoneaceae), an Amazon plant with medicinal properties.
AB  - Arrabidaea chica Verlot (Bignoniaceae) is an important folk medicine plant native
      to the Amazon region and used to treat anemia, hemorrhage, inflammation,
      intestinal colic, hepatitis, and skin affections. Although studies showed its
      therapeutic properties, little knowledge regarding genotoxic properties of this
      plant is available. The aim of this study was to determine the potential
      mutagenic and genotoxic/antigenotoxic effects of an A. chica chloroformic
      fraction (Ac-CF) obtained from leaves containing bioactive metabolites. The
      mutagenic effects were evaluated using the Salmonella mutagenicity assay, with
      TA98, TA97a, TA100, TA102, and TA1535 strains, with and without metabolic
      activation. In vivo mutagenic and genotoxic/antigenotoxic effects were
      investigated using the micronucleus (MN) test in bone marrow and alkaline comet
      assay in blood and liver after administration of 100, 500, or 1000 mg/kg Ac-CF in
      CF-1 mice by gavage (once a day for 3 d). In vitro antioxidant potential was
      evaluated using DPPH and xanthine/hypoxanthine assays. Ac-CF was not mutagenic in
      any of the Salmonella typhimurium strains tested and showed negative responses
      for mutagenicity and genotoxicity in mice. Further, Ac-CF displayed antigenotoxic
      effects by decreasing the oxidative DNA damage induced by hydrogen peroxide by
      greater than 50% in blood and liver. The antioxidant action detected in the in
      vitro assays demonstrated IC50 of 0.838 mg/ml in the xanthine/hypoxanthine assay
      and IC50 of 28.17 MUg/ml in the DPPH assay. In conclusion, Ac-CF did not induce
      mutagenic and genotoxic effects and was able to protect DNA against oxidative
      damage in vivo, suggesting that this fraction may not pose genetic risks,
      although further toxicology assays are necessary.

PMID- 23557237
TI  - Blood-pressure-lowering effect of glycosaminoglycan derived from Isaria
      sinclairii in spontaneously hypertensive rats.
AB  - The antihypertensive effects of both extracts and glycosaminoglycan derived from
      Isaria sinclairii (IS) were investigated in a spontaneously hypertensive rat
      (SHR) model. Groups of rats were treated orally with 30 mg/kg each of: (1) saline
      control or extracts of (2) water-IS (3) methanol-IS, (4) butanol-IS, (5) ethyl
      acetate-IS, or (6) captopril as positive control. The 30-mg/kg dose was
      administered with a standard diet every day for a period of 2 wk. The
      antihypertensive effects of the individual extracts were in the following order:
      methanol > water > ethyl acetate > butanol. Glycosaminoglycan (GAG) obtained from
      IS as a water-soluble alcohol precipitation fraction produced an antihypertensive
      effect. One month following administration of GAG derived from IS to SHR animals
      there was a marked decrease in systolic blood pressure from 183 to 105 mm Hg and
      reduced diastolic blood pressure from 148 to 80 mm Hg compared to untreated
      control SHR rats. It was found that GAG produced an antihypertensive effect,
      which was more effective than the positive control captopril. In the SHR animal
      model a fall of 19% in body weight was observed in the group that received GAG.
      Data thus indicate that GAG derived from I. sinclairii may be a potent, naturally
      occurring antihypertensive agent.

PMID- 23557238
TI  - Winter ventilation rates at primary schools: comparison between Portugal and
      Finland.
AB  - This study focused on examination of ventilation rates in classrooms with two
      different types of ventilation systems: natural and mechanical. Carbon dioxide
      (CO2) measurements were conducted in primary schools of Portugal characterized by
      natural ventilation and compared to Finland where mechanical ventilation is the
      norm. The winter period was selected since this season exerts a great influence
      in naturally ventilated classrooms, where opening of windows and doors occurs due
      to outdoor atmospheric conditions. The ventilation rates were calculated by
      monitoring CO2 concentrations generated by the occupants (used as a tracer gas)
      and application of the buildup phase method. A comparison between both countries'
      results was conducted with respect to ventilation rates and how these levels
      corresponded to national regulatory standards. Finnish primary schools (n = 2)
      registered a mean ventilation rate of 13.3 L/s per person, which is higher than
      the recommended ventilation standards. However, the Finnish classroom that
      presented the lowest ventilation rate (7.2 L/s per person) displayed short-term
      CO2 levels above 1200 ppm, which is the threshold limit value (TLV) recommended
      by national guidelines. The Portuguese classrooms (n = 2) showed low ventilation
      rates with mean values of 2.4 L/s per person, which is markedly lower than the
      minimum recommended value of 7 L/s per person as defined by ASHRAE and 20% less
      than the REHVA minimum of 3 L/s per person. Carbon dioxide levels of 1000 ppm,
      close to the TLV of 1200 ppm, were also reached in both Portuguese classrooms
      studied. The situation in Portugal indicates a potentially serious indoor air
      quality problem and strengthens the need for intervention to improve ventilation
      rates in naturally ventilated classrooms.

PMID- 23557239
TI  - Comparison of ActiGraph activity monitors in persons with multiple sclerosis and
      controls.
AB  - PURPOSE: The current study compared output from the vertical axis of two models
      of ActiGraph accelerometers under free-living and laboratory conditions in
      persons with multiple sclerosis (MS) and matched controls. METHOD: The sample
      included 41 cases of MS and 41 controls matched by age, sex, height and weight.
      Participants concurrently wore 7164 and GT3X accelerometers for 6 days under free
      living conditions, and undertook up to five, 6-minute periods of walking at five
      speeds on a motor-driven treadmill. RESULTS: Under free-living conditions, there
      was substantial, but not absolute, agreement (Intraclass correlation = 0.983)
      between devices and the output from the model 7164 accelerometer was
      significantly greater (p < 0.01) than that of the GT3X, resulting in a 7.0%
      difference between devices. The treadmill-walking conditions indicated that this
      difference in output between accelerometers was based on slow-walking speeds
      where there was a statistically significant (p < 0.01) and 30.3% discrepancy.
      CONCLUSIONS: The ActiGraph model 7164 and GT3X accelerometers are not
      interchangeable under free-living conditions, and the discrepancy in measurement
      between devices might be explained by the difference in output under slow-walking
      conditions. Researchers and clinicians should be aware of the difference in
      output between generations of ActiGraph accelerometers, and perhaps other brands,
      in future applications involving persons with MS and controls.

PMID- 23557240
TI  - Grip and load force coordination in cyclical isometric manipulation task is not
      affected by the feedback type.
AB  - BACKGROUND: The relationship between normal and tangential force components (grip
      force - GF and load force - LF, respectively) acting on the digits-object
      interface during object manipulation reveals neural mechanisms involved in
      movement control. Here, we examined whether the feedback type provided to the
      participants during exertion of LF would influence GF-LF coordination and task
      performance. METHODS: Sixteen young (24.7 +/-3.8 years-old) volunteers
      isometrically exerted continuously sinusoidal F(Z) (vertical component of LF) by
      pulling a fixed instrumented handle up and relaxing under two feedback
      conditions: targeting and tracking. In targeting condition, F(Z) exertion range
      was determined by horizontal lines representing the upper (10 N) and lower (1 N)
      targets, with frequency (0.77 or 1.53 Hz) dictated by a metronome. In tracking
      condition, a sinusoidal template set at similar frequencies and range was
      presented and should be superposed by the participants' exerted F(Z). Task
      performance was assessed by absolute errors at peaks (AE(Peak)) and valleys
      (AE(Valley)) and GF-LF coordination by GF-LF ratios, maximum cross-correlation
      coefficients (r(max)), and time lags. RESULTS: The results revealed no effect of
      feedback and no feedback by frequency interaction on any variable. AE(Peak) and
      GF-LF ratio were higher and r(max) lower at 1.53 Hz than at 0.77 Hz. CONCLUSION:
      These findings indicate that the type of feedback does not influence task
      performance and GF-LF coordination. Therefore, we recommend the use of tracking
      tasks when assessing GF-LF coordination during isometric LF exertion in
      externally fixed instrumented handles because they are easier to understand and
      provide additional indices (e.g., RMSE) of voluntary force control.

PMID- 23557241
TI  - Biochemical and haematological assessment of toxic effects of the leaf ethanol
      extract of Petroselinum crispum (Mill) Nyman ex A.W. Hill (Parsley) in rats.
AB  - BACKGROUND: Petroselinum crispum, a bright green biennial shrub is widely used
      traditionally as a food additive and herbal remedies for many ailments. This
      study therefore aimed to assess the toxic effects of its leaf extract using some
      biochemical, haematological parameters. METHODS: The toxic effects were assessed
      by quantifying liver enzymes such as serum aspartate amino transferase (AST),
      alanine amino transferase (ALT), alkaline phosphatase (ALP), total serum protein
      and liver weight. Effects on haematological parameters were assessed by analysis
      of parked cell volume (PCV), red blood cell count (RBC), white blood cells (WBC)
      and haemoglobin (Hb) concentrations. Histopathological studies were done on the
      liver and kidneys. RESULTS: The extract caused significant increase in serum
      activity of alanine amino transferase and blood urea nitrogen (BUN) levels at the
      dose of 1000 mg/kg. Other biochemical and haematological parameters were not
      affected at lower doses. Conversely, the liver weight was not affected after
      eight weeks of treatment at the dose levels studied. The organs obtained for
      pathological study, were structurally unchanged under histopathological
      evaluation at lower doses but inflammatory and necrotic features were observed at
      doses >= 1000 mg/kg. CONCLUSION: The results indicate that the leaf ethanol
      extract of Petroselinum crispum was hepatotoxic and nephrotoxic at continued oral
      doses equal to or more than 1000 mg/kg, but no obvious toxicity when used at
      lower doses. Therefore, there should be caution in its administration to avoid
      overdosing and known interaction with some medications. In addition, the plant
      should be kept away from pets and domestic animals and should not be cultivated
      on soil irrigated with waste water due to their ability to bio-accumulate toxic
      metals.

PMID- 23557243
TI  - Low-temperature spectroscopic properties of the peridinin-chlorophyll a-protein
      (PCP) complex from the coral symbiotic dinoflagellate Symbiodinium.
AB  - The spectroscopic properties of the peridinin-chlorophyll a-protein (PCP) from
      the coral symbiotic dinoflagellate Symbiodinium have been characterized by
      application of various ultrafast optical spectroscopies including femto- and
      nanosecond time-resolved absorption and picosecond time-resolved fluorescence
      (TRF) at 77 K. Excited state properties of peridinin and Chl a and their
      intramolecular interaction characteristics have been obtained from global fitting
      analysis and directed kinetic modeling of the data sets and compared to their
      counterparts known for the PCP from Amphidinium carterae. The lifetimes of the
      excited state of peridinin show close agreement with those known for the
      counterpart PCP, demonstrating that molecular interactions have the same
      characteristics in both complexes. More variances have been recorded for the
      excited state properties of Chl a including elongation of both the intramolecular
      energy transfer time between Chl's within the pair in the protein monomer and the
      excited state lifetime of the long wavelength form of Chl a (terminal acceptor).
      Kinetic modeling of formation of the peridinin triplet state has shown that the
      PCP is protected from potential photodamage due to an extremely fast peridinin
      triplet state formation of kTT = (14.4 +/- 2.3) * 10(9) s(-1) ((70 +/- 12)(-1)
      (ps)(-1)) that guarantees instantaneous depletion of Chl a triplets and prevents
      formation of harmful singlet oxygen ((1)DeltagO2). 

PMID- 23557242
TI  - Efficacy of iloprost and montelukast combination on spinal cord
      ischemia/reperfusion injury in a rat model.
AB  - BACKGROUND: The thoracic or thoracoabdominal aortic aneurysm surgery may cause
      spinal cord ischemia because of aortic cross-clamping and may result in severe
      postoperative complications caused by spinal cord injury. Ischemia/reperfusion
      injury may directly or indirectly be responsible for these complications. In this
      study we sought to determine whether combination of iloprost and montelukast can
      reduce the ischemia/reperfusion injury of spinal cord in a rat model. METHODS:
      Medulla spinalis tissue concentrations of interleukin-6 (IL-6), myeloperoxidase
      (MPO) and heat shock protein 70 (HSP-70) were determined in 3 groups of Spraque
      Dawley rats: control group (operation with cross clamping and intraperitoneal
      administration of 0.9% saline, n = 7), sham group (operation without cross
      clamping, n = 7), and study group (operation with cross-clamping and
      intraperitoneal administration of iloprost (25 ng/kg) and montelukast (1 mg/kg),
      n = 7). The abdominal aorta was clamped for 45 minutes, with a proximal (just
      below the left renal artery) and a distal (just above the aortic bifurcation)
      clip in control and study groups. Hindlimb motor functions were evaluated at 6,
      12, 24, and 48 hours using the Motor Deficit Index score. All rats were
      sacrificed 48 hours after the procedure and spinal cord tissue levels of
      myeloperoxidase, interleukin-6, and heat shock protein (HSP-70) were evaluated as
      markers of oxidative stress and inflammation. Histopathological analyses of
      spinal cord were also performed. RESULTS: The tissue level of HSP-70 was found to
      be similar among the 3 groups, however, MPO was highest and IL-6 receptor level
      was lowest in the control group (p = 0.007 and p = 0.005; respectively). In
      histopathological examination, there was no significant difference among the
      groups with respect to the neuronal cell degeneration, edema, or inflammation,
      but vascular congestion was found to be significantly more prominent in the
      control group than in the sham or in the study group (p = 0.05). Motor deficit
      index scores at 24 and 48 hours after ischemia were significantly lower in the
      study group than in the control group. CONCLUSION: This study suggests that
      combined use of iloprost and montelukast may reduce ischemic damage in transient
      spinal cord ischemia and may provide better neurological outcome.

PMID- 23557245
TI  - Ectopic hidradenoma papilliferum dermoscopically mimicking a blue nevus: a case
      report and review of the literature.

PMID- 23557244
TI  - Acute delivery of EphA4-Fc improves functional recovery after contusive spinal
      cord injury in rats.
AB  - Blocking the action of inhibitory molecules at sites of central nervous system
      injury has been proposed as a strategy to promote axonal regeneration and
      functional recovery. We have previously shown that genetic deletion or
      competitive antagonism of EphA4 receptor activity promotes axonal regeneration
      and functional recovery in a mouse model of lateral hemisection spinal cord
      injury. Here we have assessed the effect of blocking EphA4 activation using the
      competitive antagonist EphA4-Fc in a rat model of thoracic contusive spinal cord
      injury. Using a ledged tapered balance beam and open-field testing, we observed
      significant improvements in recovery of locomotor function after EphA4-Fc
      treatment. Consistent with functional improvement, using high-resolution ex vivo
      magnetic resonance imaging at 16.4T, we found that rats treated with EphA4-Fc had
      a significantly increased cross-sectional area of the dorsal funiculus caudal to
      the injury epicenter compared with controls. Our findings indicate that EphA4-Fc
      promotes functional recovery following contusive spinal cord injury and provides
      further support for the therapeutic benefit of treatment with the competitive
      antagonist in acute cases of spinal cord injury.

PMID- 23557246
TI  - Generation and in vivo characterization of a chimeric alphavbeta5-targeting
      antibody 14C5 and its derivatives.
AB  - BACKGROUND: Previous studies showed that radiolabeled murine monoclonal antibody
      (mAb) 14C5 and its Fab and F(ab')2 fragments, targeting alphavbeta5 integrin,
      have promising properties for diagnostic and therapeutic applications in cancer.
      To diminish the risk of generating a human anti-mouse antibody response in
      patients, chimeric variants were created. The purpose of this study was to
      recombinantly produce chimeric antibody (chAb) derivatives of the murine mAb 14C5
      and to evaluate the in vitro and in vivo characteristics. METHODS: In vitro
      stability, specificity, and affinity of radioiodinated chAb and fragments (Iodo
      Gen method) were examined on high-expressing alphavbeta5 A549 lung tumor cells.
      In vivo biodistribution and pharmacokinetic characteristics were studied in A549
      lung tumor-bearing Swiss Nu/Nu mice. RESULTS: Saturation binding experiments
      revealed high in vitro affinity of radioiodinated chAb, F(ab')2, and Fab, with
      dissociation constants (KD) of 1.19 +/- 0.19, 0.68 +/- 0.10, and 2.11 +/- 0.58
      nM, respectively. ChAb 14C5 showed highest tumor uptake (approximately 10%ID/g)
      at 24 h post injection, corresponding with other high-affinity Abs. ChF(ab')2 and
      chFab fragments showed faster clearance from the blood compared to the intact Ab.
      CONCLUSIONS: The chimerization of mAb 14C5 and its fragments has no or negligible
      effect on the properties of the antibody. In vitro and in vivo properties show
      that the chAb 14C5 is promising for radioimmunotherapy, due to its high maximum
      tumor uptake and its long retention in the tumor. The chF(ab')2 fragment shows a
      similar receptor affinity and a faster blood clearance, causing less non-specific
      retention than the chAb. Due to their fast blood clearance, the fragments show
      high potential for radioimmunodiagnosis.

PMID- 23557247
TI  - Test Your Memory (TYM) as a screening instrument in clinical practice - the
      Polish validation study.
AB  - OBJECTIVES: The Test Your Memory (TYM) test is a short, self-administered
      screening cognitive instrument designed for the detection of Alzheimer's disease
      (AD). The study was aimed to examine the Polish version of TYM as a screening
      instrument in Polish clinical practice. METHOD: In this study 199 patients were
      assessed whereas 131 patients with AD and mild cognitive impairments (MCI) and 94
      healthy control subjects took part in the final analysis. The sensitivity and
      specificity of the TYM test were evaluated among the AD group and healthy control
      group. The TYM test was compared to other neuropsychological tests, such as Mini
      Mental State Examination (MMSE), Clock Drawing Test (CDT), DemTect and Verbal
      Fluency Test (FAS). RESULTS: The average TYM score in healthy control group:
      45.4, 40.9 in the MCI patients and 23.4 in AD patients. The Polish version of the
      TYM test showed good correlation with other neuropsychological instruments among
      AD patients. Participants aged >=75 and those with primary education performed
      significantly worse in TYM. The TYM achieved the best differentiation between AD
      and the healthy control group for <=39 cut-off with a sensitivity and specificity
      of 91% and 90%, respectively. CONCLUSION: The Polish version of the TYM test is a
      useful instrument and may be seen as an alternative to the MMSE screening test in
      clinical practice in patients with dementia. However, the normative data
      suggested that the age and the level of education of the respondents should be
      considered as important factors affecting the interpretation of the final score.

PMID- 23557248
TI  - Are there changes in postural regulation across the lifespan?
AB  - The purpose was to obtain parameters of postural regulation (n = 1724) of
      asymptomatic subjects (6-97 years). The maximum postural stability and capacity
      of postural subsystems were calculated for the age ranges from 34 to 35 years
      (men) and from 38 to 44 years (women). A significant decline in postural
      performance was observed in the 40s (men) and 50s (women). Data can be used in
      the evaluation of dizziness and balance disorders in people of all ages.

PMID- 23557249
TI  - Telephone care management's effectiveness in coordinating care for Medicaid
      beneficiaries in managed care: a randomized controlled study.
AB  - OBJECTIVE: To test the effectiveness of a telephone care management intervention
      to increase the use of primary and preventive care, reduce hospital admissions,
      and reduce emergency department visits for Medicaid beneficiaries with
      disabilities in a managed care setting. DATA SOURCE: Four years (2007-2011) of
      Medicaid claims data on blind and/or disabled beneficiaries, aged 20-64. STUDY
      DESIGN: Randomized control trial with an intervention group (n = 3,540) that was
      enrolled in managed care with telephone care management and a control group (n =
      1,524) who remained in fee-for-service system without care management services.
      Multi-disciplinary care coordination teams provided telephone services to the
      intervention group to address patients' medical and social needs. DATA
      COLLECTION/EXTRACTION: Medicaid claims and encounter data for all participants
      were obtained from the state and the managed care organization. PRINCIPAL
      FINDINGS: There was no significant difference in use of primary care, specialist
      visits, hospital admissions, and emergency department between the intervention
      and the control group. Care managers experienced challenges in keeping members
      engaged in the intervention and maintaining contact by telephone. CONCLUSIONS:
      The lack of success for Medicaid beneficiaries, along with other recent studies,
      suggests that more intensive and more targeted interventions may be more
      effective for the high-needs population.

PMID- 23557251
TI  - JNK signaling maintains the mesenchymal properties of multi-drug resistant human
      epidermoid carcinoma KB cells through snail and twist1.
AB  - BACKGROUND AND METHODS: In addition to possess cross drug resistance
      characteristic, emerging evidences have shown that multiple-drug resistance (MDR)
      cancer cells exhibit aberrant metastatic capacity when compared to parental
      cells. In this study, we explored the contribution of c-Jun N-terminal kinases
      (JNK) signaling to the mesenchymal phenotypes and the aberrant motile capacity of
      MDR cells utilizing a well characterized MDR cell line KB/VCR, which is
      established from KB human epidermoid carcinoma cells by vincristine (VCR), and
      its parental cell line KB. RESULTS: Taking advantage of experimental strategies
      including pharmacological tool and gene knockdown, we showed here that
      interference with JNK signaling pathway by targeting JNK1/2 or c-Jun reversed the
      mesenchymal properties of KB/VCR cells to epithelial phenotypes and suppressed
      the motile capacity of KB/VCR cells, such as migration and invasion. These
      observations support a critical role of JNK signaling in maintaining the
      mesenchymal properties of KB/VCR cells. Furthermore, we observed that JNK
      signaling may control the expression of both snail and twist1 in KB/VCR cells,
      indicating that both snail and twist1 are involved in controlling the mesenchymal
      characteristics of KB/VCR cells by JNK signaling. CONCLUSION: JNK signaling is
      required for maintaining the mesenchymal phenotype of KB/VCR cells; and JNK
      signaling may maintain the mesenchymal characteristics of KB/VCR cells
      potentially through snail and twist1.

PMID- 23557252
TI  - Reliability of ultrasound to measure morphology of the toe flexor muscles.
AB  - BACKGROUND: Measuring the strength of individual foot muscles is very
      challenging; however, measuring muscle morphology has been shown to be associated
      with strength. A reliable method of assessing foot muscle atrophy and hypertrophy
      would therefore be beneficial to researchers and clinicians. Thus, the aim of
      this study was to evaluate the test-retest intra-observer reliability of
      ultrasound to measure the morphology of the primary toe flexor muscles. METHOD:
      The abductor hallucis, flexor hallucis brevis, flexor digitorum brevis, quadratus
      plantae and abductor digiti minimi muscles in the foot, and the flexor digitorum
      longus and flexor hallucis longus muscles in the shank were assessed in five
      males and five females (mean age = 32.1 +/- 10.1 years). Muscles were imaged
      using a GE Venue 40 ultrasound (6-9 or 7.6-10.7 MHz transducer) in a random
      order, and on two occasions 1-6 days apart. Muscle thickness and cross-sectional
      area were measured using Image J software with the assessor blinded to muscle and
      day of scan. Intraclass correlation coefficients (ICC) and limits of agreement
      were calculated to assess day-to-day repeatability of the measurements. RESULTS:
      The method was found to have good reliability (ICC = 0.89-0.99) with limits of
      agreement between 8-28% of the relative muscle size. CONCLUSION: The protocol
      described in this paper showed that ultrasound is a reliable method to measure
      morphology of the toe flexor muscles. The portability and advantages of
      ultrasound make it a useful tool for clinical and research settings.

PMID- 23557253
TI  - Promoting toddlers' positive social-emotional outcomes in low-income families: a
      play-based experimental study.
AB  - This multimethod study of mothers and toddlers (a) examined the effectiveness of
      a play-based intervention (child-oriented play vs. play-as-usual) on children's
      cooperation with their mothers and socioemotional competence; (b) introduced a
      robust new measure of maternal engagement in the intervention, reflected in the
      dose of child-oriented play the mother delivered to the child; and (c) examined
      ecological factors that predicted maternal engagement, and the effect of
      engagement on the outcomes. Low-income mothers (N = 186, 11% Latino, 27%
      minority) were randomized into child-oriented play group or play-as-usual group,
      participated in 8 play sessions, and played daily with their children for 10
      weeks. Microscopic coding of mothers' behavior in play sessions assessed the dose
      of child-oriented play delivered to children; mothers' diaries assessed time in
      daily play. Children's cooperation with maternal control, observed in the
      laboratory, and mother-rated competence were measured before randomization
      (Pretest), after play sessions (Posttest 1), and 6 months later (Posttest 2).
      Children in both groups made significant gains in both outcomes. The gains in
      cooperation appeared longer lasting in child-oriented play group. Both groups
      made significantly greater gains than a "historical community control" group, an
      unrelated longitudinal study without any intervention. Structural equation
      analyses revealed that married mothers and those with fewer children delivered
      higher doses of child-oriented play, and those doses predicted children's higher
      cooperation and competence, with the effects of earlier scores covaried. The dose
      of time spent in daily play had no effect. Child-oriented play may be a
      promising, effective, and inexpensive means of promoting toddlers' positive
      development. 

PMID- 23557254
TI  - Bi-stable resistive switching characteristics in Ti-doped ZnO thin films.
AB  - Ti-doped ZnO (ZnO/Ti) thin films were grown on indium tin oxide substrates by a
      facile electrodeposition route. The morphology, crystal structure and resistive
      switching properties were examined, respectively. The morphology reveals that
      grains are composed of small crystals. The (002) preferential growth along c-axis
      of ZnO/Ti could be observed from structural analysis. The XPS study shows the
      presence of oxygen vacancies in the prepared films. Typical bipolar and
      reversible resistance switching effects were observed. High ROFF/RON ratios
      (approximately 14) and low operation voltages within 100 switching cycles are
      obtained. The filament theory and the interface effect are suggested to be
      responsible for the resistive switching phenomenon.

PMID- 23557255
TI  - Left ventricular fibroma presenting as syncope and ventricular tachycardia.
AB  - Cardiac fibromas represent the second most common benign cardiac mass seen in the
      pediatric population, but they are rarely seen in adults. Given their large size
      and unpredictable location within the heart, patients may present with varying
      symptomatology, and in many cases, the initial presentation is sudden death. Both
      echocardiography and magnetic resonance imaging are critical to the early
      diagnosis and prompt treatment of these potentially dangerous primary tumors. We
      report a 29-year-old woman presenting with syncope and ventricular tachycardia.
      She was found to have a 5.0 cm inferoapical left ventricular fibroma, which was
      successfully resected.

PMID- 23557256
TI  - The biodiscovery potential of marine bacteria: an investigation of phylogeny and
      function.
AB  - A collection of marine bacteria isolated from a temperate coastal zone has been
      screened in a programme of biodiscovery. A total of 34 enzymes with
      biotechnological potential were screened in 374 isolates of marine bacteria. Only
      two enzymes were found in all isolates while the majority of enzyme activities
      were present in a smaller proportion of the isolates. A cluster analysis
      demonstrated no significant correlation between taxonomy and enzyme function.
      However, there was evidence of co-occurrence of some enzyme activity in the same
      isolate. In this study marine Proteobacteria had a higher complement of enzymes
      with biodiscovery potential than Actinobacteria; this contrasts with the
      terrestrial environment where the Actinobacteria phylum is a proven source of
      enzymes with important industrial applications. In addition, a number of novel
      enzyme functions were more abundant in this marine culture collection than would
      be expected on the basis of knowledge from terrestrial bacteria. There is a
      strong case for future investigation of marine bacteria as a source for
      biodiscovery.

PMID- 23557258
TI  - Cancer-associated upregulation of histone H3 lysine 9 trimethylation promotes
      cell motility in vitro and drives tumor formation in vivo.
AB  - Global histone modification patterns correlate with tumor phenotypes and
      prognostic factors in multiple tumor types. Recent studies suggest that aberrant
      histone modifications play an important role in cancer. However, the effects of
      global epigenetic rearrangements on cell functions remain poorly understood. In
      this study, we show that the histone H3 lysine 9 (H3K9) methyltransferase SUV39H1
      is clearly involved in regulating cell migration in vitro. Overexpression of wild
      type SUV39H1, but not enzymatically inactive SUV39H1, activated migration in
      breast and colorectal cancer cells. Inversely, migration was reduced by knockdown
      of SUV39H1 or chemical inhibition by chaetocin. In addition, H3K9 trimethylation
      (H3K9me3) was specifically increased in invasive regions of colorectal cancer
      tissues. Moreover, the presence of H3K9me3 positively correlated with lymph node
      metastasis in colorectal cancer patients. Furthermore, overexpression of SUV39H1
      drove tumorigenesis in mouse, resulting in a considerable decrease in survival
      rate. These data indicate that H3K9 trimethylation plays an important role in
      human colorectal cancer progression, possibly by promoting collective cell
      invasion.

PMID- 23557259
TI  - Inhibition of p38MAPK and CD137 signaling reduce dengue virus-induced TNF-alpha
      secretion and apoptosis.
AB  - BACKGROUND: Hepatic injury in dengue virus (DENV) infection is authenticated by
      hepatomegaly and an upsurge in transaminase levels. DENV replicates in
      hepatocytes and causes hepatocyte apoptosis both in vitro and in vivo.
      Understanding the molecular mechanisms of DENV-induced hepatic injury could
      facilitate the development of alternate chemotherapeutic agents and improved
      therapies. FINDINGS: The p38 mitogen-activated protein kinase (MAPK) participates
      in both apoptosis-related signaling and pro- inflammatory cytokine production.
      The role of p38 MAPK in DENV-infected HepG2 cells was examined using RNA
      interference. The results showed that DENV infection activated p38 MAPK and
      induced apoptosis. The p38 MAPK activation and TNF-alpha production were
      controlled by p38 MAPK and CD137 signaling in DENV-infected HepG2 cells as
      activated p38 MAPK, TNF-alpha and apoptosis were significantly decreased in p38
      MAPK and CD137 depleted DENV-infected HepG2 cells. Addition of exogenous TNF
      alpha to p38 MAPK depleted DENV-infected HepG2 cells restored DENV-induced
      apoptosis in HepG2 cells. CONCLUSION: DENV induces CD137 signaling to enhance
      apoptosis by increasing TNF-alpha production via activation of p38 MAPK.

PMID- 23557257
TI  - The transcriptome of Leishmania major in the axenic promastigote stage:
      transcript annotation and relative expression levels by RNA-seq.
AB  - BACKGROUND: Although the genome sequence of the protozoan parasite Leishmania
      major was determined several years ago, the knowledge of its transcriptome was
      incomplete, both regarding the real number of genes and their primary structure.
      RESULTS: Here, we describe the first comprehensive transcriptome analysis of a
      parasite from the genus Leishmania. Using high-throughput RNA sequencing (RNA
      seq), a total of 10285 transcripts were identified, of which 1884 were considered
      novel, as they did not match previously annotated genes. In addition, our data
      indicate that current annotations should be modified for many of the genes. The
      detailed analysis of the transcript processing sites revealed extensive
      heterogeneity in the spliced leader (SL) and polyadenylation addition sites. As a
      result, around 50% of the genes presented multiple transcripts differing in the
      length of the UTRs, sometimes in the order of hundreds of nucleotides. This
      transcript heterogeneity could provide an additional source for regulation as the
      different sizes of UTRs could modify RNA stability and/or influence the
      efficiency of RNA translation. In addition, for the first time for the Leishmania
      major promastigote stage, we are providing relative expression transcript levels.
      CONCLUSIONS: This study provides a concise view of the global transcriptome of
      the L. major promastigote stage, providing the basis for future comparative
      analysis with other development stages or other Leishmania species.

PMID- 23557260
TI  - Introducing TAMI: an objective test of ability in movement imagery.
AB  - Individual ability in mental imagery varies widely across individuals, leading to
      the development of questionnaires to evaluate mental imagery. Within the domain
      of movement imagery, questionnaires have previously relied on subjective ratings
      of vividness, which may be influenced by additional factors such as motor skill
      confidence, success of imagined actions, and social desirability. These
      additional factors are of particular importance when making comparisons between
      samples from different populations, such as athletes versus nonathletes and
      patients versus healthy individuals. The authors present a novel test of ability
      in movement imagery (Test of Ability in Movement Imagery [TAMI]) that relies on
      objective measures and requires participants to make explicit imagined movements
      from an external perspective. In Study 1, the authors present evidence that young
      adults perform at a mid-level on the TAMI. In Study 2, they further compare
      performance on the TAMI with a battery of other measures to better characterize
      the TAMI by determining its similarities and differences with existing measures.
      The findings of both studies indicate the TAMI to be a valid and reliable measure
      of movement imagery ability. The authors additionally discuss future applications
      of the TAMI to athletic and clinical research.

PMID- 23557261
TI  - Identifying coordinative structure using principal component analysis based on
      coherence derived from linear systems analysis.
AB  - Principal component analysis is a powerful and popular technique for capturing
      redundancy in muscle activity and kinematic patterns. A primary limitation of the
      correlations or covariances between signals on which this analysis is based is
      that they do not account for dynamic relations between signals, yet such
      relations-such as that between neural drive and muscle tension-are widespread in
      the sensorimotor system. Low correlations may thus be obtained and signals may
      appear independent despite a dynamic linear relation between them. To address
      this limitation, linear systems analysis can be used to calculate the matrix of
      overall coherences between signals, which measures the strength of the relation
      between signals taking dynamic relations into account. Using ankle, knee, and hip
      sagittal-plane angles from 6 healthy subjects during ~50% of total variance in
      the data set, while with overall coherence matrices the first component accounted
      for > 95% of total variance. The results demonstrate that the dimensionality of
      the coordinative structure can be overestimated using conventional correlation,
      whereas a more parsimonious structure is identified with overall coherence.

PMID- 23557262
TI  - Emerging concepts of dietary therapy for pediatric and adult eosinophilic
      esophagitis.

PMID- 23557263
TI  - Spondyloarthropathy: frontier for molecular targets?

PMID- 23557265
TI  - Immune-mediated inflammatory diseases: progress in molecular pathogenesis and
      therapeutic strategies.
AB  - The European Workshop on Immune-Mediated Inflammatory Diseases aims to exchange
      scientific knowledge and promote the collaboration between various disciplines
      (rheumatology, dermatology and gastroenterology) among physicians and scientists.
      This year ophthalmologists and neurologists were also present for the first time.
      The meeting revolved around the following topics: fibrosis, gene therapy in
      ophthalmology, functional genomics, challenges in human immunology, environmental
      factors, diabetes and metabolism, novelties in multiple sclerosis and innate
      lymphoid cells. The workshop was preceded by a masterclass that covered the last
      15 years of IL-17/Th17 research and provided an overview on future therapeutics
      to battle immune-mediated inflammatory diseases.

PMID- 23557266
TI  - Leukocyte traffic control: a novel therapeutic strategy for inflammatory bowel
      disease--an update.
AB  - Adhesion molecules play a key role in the pathogenetic mechanisms of inflammatory
      bowel disease (IBD), both in Crohn's disease (CD) and ulcerative colitis (UC). In
      the last decade, some progress has been made in understanding their key role in
      leukocyte trafficking control in terms of basic research, but evidence of
      clinical efficacy is lacking. In the last 2 years, new molecules directed against
      integrins and integrin receptors have been developed and investigated in clinical
      trials, showing that anti-alpha4beta7 integrin agents can be effective and safe
      for the induction and maintenance of remission in active CD and UC. Preliminary
      data show that anti-MAdCAM, anti-beta7 and anti-integrin receptor agents are not
      all effective in IBD. Such results open new perspectives on clinical management
      of IBD, and new directions in understanding the role of adhesion molecules and
      leukocyte recruitment both in CD and UC.

PMID- 23557267
TI  - Systems level immune response analysis and personalized medicine.
AB  - The immune system is an anatomically structured, orchestrated interaction of
      different cell types that communicate via a large number of receptors recognizing
      both soluble and cellular ligands. Recent technological advances now allow large
      scale measurements for better appreciation of this complexity. Despite these
      advances, only a few immunological parameters are routinely measured in clinical
      practice. The authors believe that these measurements are insufficient to
      describe the immune function of individual patients and thus cannot be used to
      evaluate immune-mediated diseases or response to therapy. Our current knowledge
      of immunology comes largely from work in murine model systems where the immune
      system has been characterized in great detail. This impressive volume of
      knowledge has proven to be difficult to translate into novel therapies in humans;
      one reason for this is the lack of large-scale immune monitoring allowing for
      systems-wide analysis of the human immune system. The authors propose a systems
      approach to immunology, where the focus is moved from analysis of individual cell
      types towards more integrated studies of the entire immune system. Exercising
      'systems immunology' in preclinical research, during drug development and in
      patients undergoing therapies affecting the immune system, will enable us to
      improve clinical results through personalized medicine and help to define
      clinically relevant patterns of immune reactivity.

PMID- 23557268
TI  - The genetic basis of resistance to HIV infection and disease progression.
AB  - Susceptibility to HIV infection and the modulation of disease progression are
      strictly dependent on inter-individual variability, much of which is secondary to
      host genetic heterogeneity. The study of host factors that control these
      phenomena relies not only on candidate gene approaches but also on unbiased
      genome-wide genetic and functional analyses. Additional new insights stem from
      the study of mechanisms that control the expression of host and viral genes, such
      as miRNA. The genetic host factors that have been suggested to be associated
      either with resistance to HIV-1 infection or with absent/delayed progression to
      AIDS are nevertheless unable to fully justify the phenomenon of differential
      susceptibility to HIV. Multidisciplinary approaches are needed to further analyze
      individuals who deviate from the expected response to HIV exposure/infection.
      Results of these analyses will facilitate the identification of novel targets
      that could be exploited in the setting up of innovative therapeutic or vaccine
      approaches.

PMID- 23557269
TI  - Importance of reverse signaling of the TNF superfamily in immune regulation.
AB  - TNF-related ligands (with the exception of lymphotoxin-alpha) are synthesized as
      type II transmembrane proteins, though many of them also have soluble forms. An
      increasing number of publications report that these 'ligands' behave as
      receptors, activating intracellular signaling pathways when interacting with
      cognate 'receptors' or agonistic antibodies. Most members of the TNF family and
      their receptors influence survival, proliferation, differentiation or activation
      of immune cells. The elicited 'reverse signals' also have significant importance.
      They proved to be involved in the activation of APCs, T and B cells,
      differentiation of osteoclasts and apoptosis of activated macrophages. They
      influence the balance between destructive immune response and tolerance. Several
      examples show that therapeutic manipulation of the reverse signal can help to
      treat malignancies as well as autoimmune disorders.

PMID- 23557270
TI  - Tuberculosis in the course of sarcoidosis treatment: is genotyping necessary for
      personalized therapy?
AB  - Pathological similarities between sarcoidosis (SA) and tuberculosis (TB) suggest
      that mycobacterial antigen(s), in genetically different predisposed hosts, may be
      a cause of SA. The authors' work and other published comparative analyses of HLA
      and non-HLA alleles in patients with SA or TB from different ethnic groups in the
      world revealed that some antigens were connected with high risk of SA or TB
      development, but others were comparable in both patient populations. The authors
      also showed a possibility of predominant occurrence of HLA alleles characteristic
      for TB as a cause of TB in patients with SA on corticosteroid therapy. It is
      possible that an analysis of SA and TB patient's genetic background may be
      helpful for protection from TB in SA patients on corticosteroids, especially on
      anti-TNF-alpha treatment. The authors suggest that the consideration of an
      immunosuppressive therapy in SA patients will need more attention and individual
      therapy based on genotyping study.

PMID- 23557271
TI  - Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome):
      clinical and immunological spectrum.
AB  - An adjuvant is a substance that enhances the antigen-specific immune response,
      induces the release of inflammatory cytokines, and interacts with Toll-like
      receptors and the NALP3 inflammasome. The immunological consequence of these
      actions is to stimulate the innate and adaptive immune response. The activation
      of the immune system by adjuvants, a desirable effect, could trigger
      manifestations of autoimmunity or autoimmune disease. Recently, a new syndrome
      was introduced, autoimmune/inflammatory syndrome induced by adjuvants (ASIA),
      that includes postvaccination phenomena, macrophagic myofasciitis, Gulf War
      syndrome and siliconosis. This syndrome is characterized by nonspecific and
      specific manifestations of autoimmune disease. The main substances associated
      with ASIA are squalene (Gulf War syndrome), aluminum hydroxide (postvaccination
      phenomena, macrophagic myofasciitis) and silicone with siliconosis. Mineral oil,
      guaiacol and iodine gadital are also associated with ASIA. The following review
      describes the wide clinical spectrum and pathogenesis of ASIA including defined
      autoimmune diseases and nonspecific autoimmune manifestations, as well as the
      outlook of future research in this field.

PMID- 23557272
TI  - Exclusive enteral nutrition and induction of remission of active Crohn's disease
      in children.
AB  - Exclusive enteral nutrition is an effective therapy for the management of active
      Crohn's disease, especially in children and adolescents. This therapeutic
      approach involves the use of a liquid nutritional product with the exclusion of
      normal diet for a period of many weeks. Although recent studies have helped to
      delineate some aspects of how exclusive enteral nutrition should be used, there
      remain many gaps in our understanding. In addition, several recent reports have
      provided intriguing insights into the mechanisms of this nutritional approach.

PMID- 23557273
TI  - Sublingual immunotherapy in preschool children: an update.
AB  - Allergen immunotherapy is a subject widely debated by allergists. Currently,
      there are controversial discussions focused on the sublingual route. Sublingual
      immunotherapy (SLIT) has so far been used in Europe, Asia and Australia for the
      treatment of allergic respiratory diseases. The minimum age to start specific
      immunotherapy with inhalant allergens in children has not been clearly
      established, and position papers discourage its use in children younger than 5
      years of age. Nevertheless, it is known that SLIT efficacy is higher when SLIT is
      started at an earlier age. The aim of this review is to focus on studies in
      preschool children evaluating SLIT safety and efficacy, in order to improve this
      practice at an earlier age in childhood.

PMID- 23557275
TI  - Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower.
AB  - BACKGROUND: Chrysanthemum indicum L. flower (CIF) has been widely used as tea in
      Korea. This study aims to investigate the hepatoprotective effect of the hot
      water extract of CIF (HCIF) in in vitro and in vivo systems. METHODS:
      Hepatoprotective activities were evaluated at 250 to 1000 MUg/mL concentrations
      by an in vitro assay using normal human hepatocytes (Chang cell) and
      hepatocellular carcinoma cells (HepG2) against CCl4-induced cytotoxicity.
      Cytochrome P450 2E1, which is a key indicator of hepatic injury, was detected by
      western blot analysis using rabbit polyclonal anti-human CYP2E1 antibody. An in
      vivo hepatoprotective activity assay was performed at 1000 to 4000 MUg/mL
      concentrations on CCl4-induced acute toxicity in rats, and the serum levels of
      glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT),
      alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined by
      standard enzyme assays. RESULTS: The hepatoprotective effects of HCIF
      significantly reduced the levels of GOT (60.1%, P = 0.000) and GPT (64.5%, P =
      0.000) compared with the vehicle control group (CCl4 alone). The survival rates
      of HepG2 and Chang cells were significantly improved compared with the control
      group [82.1% (P = 0.034) and 62.3% (P = 0.002), respectively]. HCIF [50 mg/kg
      body weight (BW)] treatment significantly reduced the serum levels of GOT (49.5%,
      P = 0.00), GPT (55.5%, P = 0.00), ALP (30.8%, P = 0.000) and LDH (45.6%, P =
      0.000) compared with the control group in this in vivo study. The expression
      level of cytochrome P450 2E1 (CYP2E1) protein was also significantly decreased at
      the same concentration (50 mg/kg BW; P = 0.018). CONCLUSION: HCIF inhibited
      bioactivation of CCl4-induced hepatotoxicity and downregulates CYP2E1 expression
      in vitro and in vivo.

PMID- 23557276
TI  - Efficient techniques for genotype-phenotype correlational analysis.
AB  - BACKGROUND: Single Nucleotide Polymorphisms (SNPs) are sequence variations found
      in individuals at some specific points in the genomic sequence. As SNPs are
      highly conserved throughout evolution and within a population, the map of SNPs
      serves as an excellent genotypic marker. Conventional SNPs analysis mechanisms
      suffer from large run times, inefficient memory usage, and frequent
      overestimation. In this paper, we propose efficient, scalable, and reliable
      algorithms to select a small subset of SNPs from a large set of SNPs which can
      together be employed to perform phenotypic classification. METHODS: Our
      algorithms exploit the techniques of gene selection and random projections to
      identify a meaningful subset of SNPs. To the best of our knowledge, these
      techniques have not been employed before in the context of genotype-phenotype
      correlations. Random projections are used to project the input data into a lower
      dimensional space (closely preserving distances). Gene selection is then applied
      on the projected data to identify a subset of the most relevant SNPs. RESULTS: We
      have compared the performance of our algorithms with one of the currently known
      best algorithms called Multifactor Dimensionality Reduction (MDR), and Principal
      Component Analysis (PCA) technique. Experimental results demonstrate that our
      algorithms are superior in terms of accuracy as well as run time. CONCLUSIONS: In
      our proposed techniques, random projection is used to map data from a high
      dimensional space to a lower dimensional space, and thus overcomes the curse of
      dimensionality problem. From this space of reduced dimension, we select the best
      subset of attributes. It is a unique mechanism in the domain of SNPs analysis,
      and to the best of our knowledge it is not employed before. As revealed by our
      experimental results, our proposed techniques offer the potential of high
      accuracies while keeping the run times low.

PMID- 23557277
TI  - The Zeitraffer phenomenon, akinetopsia, and the visual perception of speed of
      motion: a case report.
AB  - The Zeitraffer phenomenon is the altered perception of the speed of moving
      objects. A single case is reported using the subject's own description of a
      transient alteration of the visual perception of motion. The literature on the
      subject is reviewed. The Zeitraffer phenomenon probably arises from dysfunction
      of brain networks subserving visual perception of speed. It shares
      characteristics with akinetopsia, the loss of visual ability to perceive motion. 

PMID- 23557278
TI  - Diagnostic reliability of the Tzanck smear in dermatologic diseases.
AB  - BACKGROUND: The Tzanck smear is a simple, easily applicable, rapid, and
      inexpensive test for the diagnosis of erosive vesiculobullous, tumoral, and
      granulomatous diseases. The diagnostic accuracy of the Tzanck smear is known, but
      its diagnostic reliability has been evaluated only in herpetic infections and
      basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the
      diagnostic reliability of the Tzanck smear in erosive vesiculobullous, tumoral,
      and granulomatous diseases. METHODS: Patients evaluated by Tzanck smear at
      Baskent University Faculty of Medicine, Department of Dermatology, between
      February 2009 and July 2010, were included. Three dermatologists were involved in
      the study. Dermatologist A performed a clinical dermatologic examination, took
      the smear material, made a clinical diagnosis, and compared the clinical and
      cytological diagnoses. Dermatologists B and C evaluated the smears. Agreement
      between the latter two dermatologists on the cytological diagnoses was
      determined. RESULTS: In 500 patients, a total of 272 (54%) erosive
      vesiculobullous, 190 (38%) tumoral, and 38 (8%) granulomatous lesions were
      diagnosed. The diagnostic reliability of the Tzanck smear was reasonably
      substantial (kappa = 0.59) for all types of lesions, substantial for erosive
      vesiculobullous (kappa = 0.79) and granulomatous (kappa = 0.68) lesions, and
      moderate (kappa = 0.50) for tumoral lesions. CONCLUSIONS: The Tzanck smear may be
      used for the evaluation of erosive vesiculobullous and granulomatous lesions with
      brief training. However, the evaluation of tumoral lesions by Tzanck smear
      requires more experience.

PMID- 23557280
TI  - Implications of increased nanoparticle absorption by infant lungs: future
      prospects.

PMID- 23557281
TI  - EPR-effect: utilizing size-dependent nanoparticle delivery to solid tumors.

PMID- 23557279
TI  - Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence
      in two dermatomyositis cohorts from Mexico City and Guadalajara.
AB  - INTRODUCTION: Autoantibodies and clinical manifestations in
      polymyositis/dermatomyositis (PM/DM) are affected by both genetic and
      environmental factors. The high prevalence of DM and anti-Mi-2 in Central America
      is thought to be associated with the high UV index of the area. The prevalences
      of autoantibodies and the clinical manifestations of PM/DM were evaluated
      comparing two cohorts in Mexico. METHODS: Ninety-five Mexican patients with PM/DM
      (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were
      characterized by immunoprecipitation using 35S-methionine labeled K562 cell
      extract. Clinical information was obtained from medical records. RESULTS: DM
      represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%),
      followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody
      profile in adult-onset DM in Mexico City versus Guadalajara showed striking
      differences: anti-Mi-2 was 59% versus 12% (P = 0.0012) whereas anti-p155/140 was
      9% versus 35% (P = 0.02), respectively. A strong association of anti-Mi-2 with DM
      was confirmed and when clinical features of anti-Mi-2 (+) DM (n = 30) versus anti
      Mi-2 (-) DM (n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was
      more common in the anti-Mi-2 (+) group (P = 0.0001). Levels of creatine
      phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they
      responded well to therapy. CONCLUSIONS: Anti-Mi-2 has a high prevalence in
      Mexican DM and is associated with the shawl sign and high CPK. The prevalence of
      anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus
      Guadalajara, which have a similar UV index. This suggests roles of factors other
      than UV in anti-Mi-2 antibody production.

PMID- 23557284
TI  - Upcycling drugs for brain-related diseases: a sustainable future for targeted
      drug delivery.

PMID- 23557285
TI  - Organic cation transporters in human nasal primary culture: expression and
      functional activity.
AB  - BACKGROUND: The majority of drugs cross epithelial cells by either passive
      diffusion or via carrier-mediated drug transporters. The aim of this study was to
      investigate the transport characteristics, protein expression and localization of
      organic cation transporters in human nasal epithelium. METHODS & RESULTS: The
      expression, localization and transport characteristics of the transporters were
      investigated using permeation, PCR and immunohistochemistry. The uptake of 4-(4
      (dimethylamino)styryl)-N-methylpyridinium iodide followed Michaelis-Menten
      kinetics. Its intracellular accumulation of the compound was inhibited by organic
      cation transporters (OCTs) and carnitine/organic cation transporter (OCTNs)
      inhibitors. Detected OCT1-3, OCTN1 and OCTN2 gene transcripts correlated with
      immunohistological staining for OCT1-3, OCTN1 and OCTN2 antibodies. Except for
      OCTN1, the antibodies were generally localized on the apical side of the
      epithelial cells. CONCLUSION: Based on the immunohistochemical and
      uptake/transport studies, we conclude that the human nasal epithelium expresses
      OCT1-3, OCTN1 and OCTN2 transporters mainly on the apical side of the nasal
      cells.

PMID- 23557286
TI  - Cholesterol domains enhance transfection.
AB  - BACKGROUND: The formation of cholesterol domains in lipoplexes has been
      associated with enhanced serum stability and transfection rates both in cell
      culture and in vivo. RESULTS: This study utilizes the ability of saturated
      phosphatidylcholines to promote the formation of cholesterol domains at much
      lower cholesterol contents than have been utilized in previous work. The results
      demonstrate that lipoplexes with identical cholesterol and cationic lipid
      contents exhibit significantly improved transfection efficiencies when a domain
      is present, consistent with previous work. In addition, studies assessing
      transfection rates in the absence of serum demonstrate that the ability of
      domains to enhance transfection is not dependent on interactions with serum
      proteins. Consistent with this hypothesis, characterization of the adsorbed
      proteins composing the corona of these lipoplex formulations did not reveal a
      correlation between transfection and the adsorption of a specific protein.
      CONCLUSION: We have demonstrated that the interaction with serum proteins can
      promote domain formation in some formulations, and thereby result in enhanced
      transfection only after serum exposure.

PMID- 23557287
TI  - Continuous processing and the applications of online tools in pharmaceutical
      product manufacture: developments and examples.
AB  - Continuous processing and production in pharmaceutical manufacturing has received
      increased attention in recent years mainly due to the industries' pressing needs
      for more efficient, cost-effective processes and production, as well as
      regulatory facilitation. To achieve optimum product quality, the traditional
      trial-and-error method for the optimization of different process and formulation
      parameters is expensive and time consuming. Real-time evaluation and the control
      of product quality using an online process analyzer in continuous processing can
      provide high-quality production with very high-throughput at low unit cost. This
      review focuses on continuous processing and the application of different real
      time monitoring tools used in the pharmaceutical industry for continuous
      processing from powder to tablets.

PMID- 23557288
TI  - Critical challenges to the design of drug-eluting medical devices.
AB  - Drug-eluting devices cover a wide variety of possible product concepts. The
      design constraints for modified or sustained local delivery technologies that are
      compatible with medical devices are quite different from those constraints with
      any conventional dosage forms. To develop a successful development strategy from
      proof-of-concept to commercialization, it is of paramount importance to assess
      how drug delivery affects the desired mechanism of action of such combination
      products. Starting at the feasibility stage, the project team must have a clear
      understanding of the performance targets expected by patients and
      physicians/surgeons. In addition, R&D staff must anticipate and proactively
      address the differences in technical, quality and regulatory requirements from
      drug delivery and medical device perspectives. Through the eyes of drug delivery,
      this article will describe common challenges encountered in the development of
      drug-eluting devices and offer relevant mitigation strategies.

PMID- 23557289
TI  - Peptide pills for brain diseases? Reality and future perspectives.
AB  - The peptide therapeutic market is one of the fastest growth areas of the
      pharmaceutical industry. Although few orally administered peptides are marketed
      and many are in different phases of clinical development, there is no marketed
      oral peptide therapeutic used for CNS disorders. The major challenges involved in
      orally delivering peptides to the brain relate to their enzymatic instability and
      inability to permeate across physiological barriers. The paucity of therapies for
      the treatment of brain diseases and the presence of the blood-brain barrier
      excluding 98% of therapeutic molecules necessitates parenteral administration.
      Various approaches have been applied to enhance oral peptide bioavailability, but
      only nanoparticulate strategies were able to deliver orally therapeutic peptides
      to the brain. Although industry may be reluctant to invest in developing oral
      peptide nanomedicines, the increasingly unmet clinical need and economic burden
      associated with brain diseases will fuel the development of the first marketed
      oral-to-brain peptide therapy.

PMID- 23557290
TI  - Recent advancements in tissue engineering for stem cell-based cardiac therapies.
AB  - Advances in cardiac tissue engineering have recently focused on utilizing stem
      cells to regenerate infarcted and scarred myocardium. Due to their proliferative
      nature and tremendous potential for differentiation, stem cells are presently
      being investigated for clinical applications. Unfortunately, limiting factors
      such as massive cell death and poor retention have hampered clinical outcomes.
      Consequently, the development of an efficient delivery system for stem cells to
      the target site is essential. The use of innovative tissue engineering techniques
      has opened up new horizons within the field of cellular cardiomyoplasty. This
      paper will present a comprehensive overview of the recent advancements in stem
      cell technology destined for myocardial tissue repair. In addition, the
      multidisciplinary approach to tissue engineering presented here will provide the
      reader with insight into the clinical realization of cellular cardiomyoplasty.

PMID- 23557292
TI  - Probing the magnetic behavior of single nanodots.
AB  - In this paper, a method is presented that has the sensitivity to measure
      magnetization behavior of single nanostructures. It is demonstrated that the
      technique gives the ability to separate different signals of single nanodots from
      a small ensemble of structures. Our method is based on the anomalous Hall-Effect
      and allows for resolving signals from spherical nanoparticles with diameter down
      to 3.5 nm. The method gives access to magnetic properties of particles in a wide
      thermal and dynamical range. The potential of the technique is demonstrated
      utilizing particles that are created from Co films sandwiched by Pt layers.

PMID- 23557293
TI  - Associations between visit-to-visit variability in blood pressure measured in the
      office and antihypertensive drugs: the J-HOME-Morning study.
AB  - The factors associated with visit-to-visit variability in blood pressure (BP)
      measured in the office between the two visits were identified in 1379 treated
      hypertensive patients (mean age, 66.1 +/- 11.0 y; women, 53.8%). Multivariate
      regression analysis showed that office BP and visit-to-visit heart rate
      variability were positively associated with visit-to-visit BP variability,
      whereas body mass index, duration of antihypertensive medication, and taking
      amlodipine were negatively associated with visit-to-visit BP variability. Further
      prospective studies are required to clarify the causal relationships between
      these factors and visit-to-visit BP variability among treated hypertensive
      patients.

PMID- 23557294
TI  - Morphological variability of black bullhead Ameiurus melas in four non-native
      European populations.
AB  - External morphology in black bullhead Ameiurus melas, a fish species considered
      to have high invasive potential, was studied in its four non-native European
      populations (British, French, Italian and Slovak). The aim of this study was to
      examine this species' variability in external morphology, including ontogenetic
      context, and to evaluate its invasive potential. Specimens from all non-native
      populations reached smaller body size compared to individuals from native
      populations. Juvenile A. melas were found to have a relatively uniform body shape
      regardless of the population's origin, whereas adults developed different
      phenotypes depending upon location. Specimens from the U.K., Slovak and French
      populations appeared to be rather similar to each other, whereas the Italian
      population showed the most distant phenotype. This probably results from the
      different thermal regime in the Italian habitat. Ameiurus melas from non-native
      European populations examined in this study showed some potential to alter the
      body shape both within and between populations. The phenotypic plasticity of A.
      melas, however, was not found to be as significant as in other invasive fish
      species. The results suggest that morphological variability itself is not
      necessarily essential for invasive success. The invasiveness of A. melas is
      therefore probably favoured by variations in its life-history traits and
      reproduction variables, together with some behavioural traits (e.g. voracious
      feeding and parental care) rather than by phenotypic plasticity expressed in
      external morphology.

PMID- 23557295
TI  - Using new electrofishing technology to amp-up fish sampling in estuarine
      habitats.
AB  - A prototype, boat-mounted electrofisher capable of operation in estuarine waters
      (where electrical conductivities often exceed 20 000 uS cm(-1)) was assessed.
      Electrofishing was compared to fyke and mesh netting in four riverine estuaries
      and to seining in a lagoonal estuary (consisting of a series of brackish coastal
      lakes separated from the sea by a barrier system of sand dunes). Fish assemblage
      composition, length distributions and the probability of detecting ecological
      fish guilds (relating to estuary use, position in the water column and body size)
      were compared among gears. The assemblage composition of electrofishing samples
      differed from those of fyke nets in all riverine estuaries and from mesh netting
      in two. The assemblage composition of electrofishing samples differed from those
      of seining in structured seagrass habitats of the lagoonal estuary. When all
      species were pooled, the electrofisher sampled a broader range of lengths than
      either fyke or mesh netting in riverine estuaries or seining in lagoonal
      estuaries. The bias of electrofishing and netting towards particular species and
      size classes affected the probability of detecting some ecological guilds,
      highlighting the potential implications of gear choice on understanding estuarine
      ecological function. The detection of guilds varied with gear type and
      environmental conditions, including stratification, water depth and surface
      electrical conductivity. Assessments with the aim to characterize the structure
      of fish assemblages will benefit from the use of multiple gears. Electrofishing
      shows immense promise for discretely sampling highly structured habitats to test
      hypotheses about their use.

PMID- 23557296
TI  - Effects of an experimental short-term cortisol challenge on the behaviour of wild
      creek chub Semotilus atromaculatus in mesocosm and stream environments.
AB  - The consequences of stress on the behaviour of wild creek chub Semotilus
      atromaculatus outside the reproductive period were studied using a single intra
      coelomic injection of cortisol, suspended in coconut butter, to experimentally
      raise plasma cortisol levels. Behaviour between cortisol-treated, sham-treated
      (injected with coconut butter) and control S. atromaculatus was compared in a
      mesocosm system, using a passive integrated transponder array, and in a natural
      stream system (excluding shams), using surgically implanted radio transmitters.
      While laboratory time-course studies revealed that the cortisol injection
      provided a physiologically relevant challenge, causing prolonged (c. 3 days)
      elevations of plasma cortisol similar to that achieved with a standardized
      chasing protocol, no differences in fine-scale movements were observed between
      cortisol-treated, sham-treated and control S. atromaculatus nor in the large
      scale movements of cortisol-treated and control S. atromaculatus. Moreover, no
      differences were observed in diel activity patterns among treatments.
      Differential mortality, however, occurred starting 10 days after treatment where
      cortisol-treated S. atromaculatus exhibited nearly twice as many mortalities as
      shams and controls. These results suggest that, although the experimental
      manipulation of cortisol titres was sufficient to cause mortality in some
      individuals, there were compensatory mechanisms that maintained behaviours (i.e.
      including activity and movement) prior to death. This study is one of the first
      to use experimental cortisol implants outside a laboratory environment and during
      the non-reproductive period and yields insight into how wild animals respond to
      additional challenges (in this case elevated cortisol) using ecologically
      meaningful endpoints.

PMID- 23557297
TI  - Provenance matters: thermal reaction norms for embryo survival among sockeye
      salmon Oncorhynchus nerka populations.
AB  - Differences in thermal tolerance during embryonic development in Fraser River
      sockeye salmon Oncorhynchus nerka were examined among nine populations in a
      controlled common-garden incubation experiment. Forcing embryonic development at
      an extreme temperature (relative to current values) of 16 degrees  C,
      representing a future climate change scenario, significantly reduced survival
      compared to the more ecologically moderate temperature of 10 degrees  C (55% v.
      93%). Survival at 14 degrees  C was intermediate between the other two
      temperatures (85%). More importantly, this survival response varied by provenance
      within and between temperature treatments. Thermal reaction norms showed an
      interacting response of genotype and environment (temperature), suggesting that
      populations of O. nerka may have adapted differentially to elevated temperatures
      during incubation and early development. Moreover, populations that historically
      experience warmer incubation temperatures at early development displayed a higher
      tolerance for warm temperatures. In contrast, thermal tolerance does not appear
      to transcend life stages as adult migration temperatures were not related to
      embryo thermal tolerance. The intra-population variation implies potential for
      thermal tolerance at the species level. The differential inter-population
      variation in thermal tolerance that was observed suggests, however, limited
      adaptive potential to thermal shifts for some populations. This infers that the
      intergenerational effects of increasing water temperatures may affect populations
      differentially, and that such thermally mediated adaptive selection may drive
      population, and therefore species, persistence.

PMID- 23557298
TI  - Specialist corallivores dominate butterflyfish assemblages in coral-dominated
      reef habitats.
AB  - This study examined the dietary habits and functional composition of
      butterflyfishes in the Chagos Archipelago, central Indian Ocean. Eighteen species
      of butterflyfishes were recorded in Chagos, including six obligate corallivores
      (Chaetodon bennetti, Chaetodon guttatissimus, Chaetodon meyeri, Chaetodon
      trifascialis, Chaetodon trifasciatus and Chaetodon zanzibarensis), five
      facultative corallivores (Chaetodon auriga, Chaetodon falcula, Chaetodon
      interruptus, Chaetodon kleinii and Chaetodon madagaskariensis), two non
      corallivores (Chaetodon lunula and Chaetodon xanthocephalus) and a further five
      species (Chaetodon citrinellus, Chaetodon lineolatus, Heimitaurichthys zoster,
      Heniochus monoceros and Forcipiger flavissimus), for which local dietary habits
      were not studied. There were marked differences in the abundance of
      butterflyfishes among sites and between reef zones, mostly associated with
      variation in abundance of scleractinian corals. Obligate coral-feeding species
      (mostly C. trifascialis) dominated across all sites. This study suggests that
      coral feeding and high levels of dietary specialization contribute to high
      population-level fitness among coral reef butterflyfishes. Despite being more
      vulnerable to habitat disturbances and coral loss, it appears likely that
      specialist coral-feeding butterflyfishes are also much more resilient to
      occasional disturbances, and therefore dominate in a wide range of coral reef
      habitats.

PMID- 23557299
TI  - Population structure and residency patterns of the blacktip reef shark
      Carcharhinus melanopterus in turbid coastal environments.
AB  - This study examined the characteristics of a blacktip reef shark Carcharhinus
      melanopterus population in turbid coastal habitats through a multi-year fishery
      independent sampling and tag-recapture programme. Results revealed a highly
      structured population comprised almost entirely of juveniles and adult females
      with individuals between 850 and 1050 mm total length effectively absent. Mature
      males were also rarely encountered with adult sex ratio highly biased towards
      females (female:male = 7:1). Mating scars were observed on adult females between
      December and April, and parturition was observed from December to March.
      Regression analysis showed that catch rates were significantly higher during the
      summer wet season between November and May. Recapture data suggested a highly
      resident population with a recapture rate of 21% and a mean recapture distance of
      0.8 km. In addition, 33% of recaptured animals were captured multiple times,
      indicating long-term residency. Most recaptures were, however, of adults with few
      juveniles recaptured. Widespread sampling at the study site and in adjacent areas
      suggested that the population was highly localized to a specific bay. The bimodal
      and sex-segregated population structure observed here differs from previous
      reports for this species, and in combination with reproductive observations,
      suggests population structuring to facilitate reproductive and recruitment
      success. These data also highlight the potential ecosystem functions performed by
      coastal habitats in sustaining C. melanopterus populations.

PMID- 23557300
TI  - Age and growth of two newly established invasive populations of Tilapia mariae in
      northern Australia.
AB  - Sagittal otoliths were used to age the samples of Tilapia mariae collected from a
      coastal river and an impoundment. Validation of sagittae checks was achieved
      using both quantitative marginal increment analysis and by tetracycline marking
      of the otoliths of fish kept in tanks and in a farm dam. The annulus pattern on
      the otoliths was generally clear and their formation appeared to be temperature
      related and largely completed in the Austral spring around September and October.
      Male T. mariae grow faster and larger than females and the maximum ages of fish
      from the coastal river and impoundment was 9+ and 4+ years, respectively. Past
      fish surveys and the absence of older age classes in the impoundment population
      would suggest that this population was only very recently established.

PMID- 23557301
TI  - Effects of life phase and schooling patterns on the foraging behaviour of coral
      reef fishes from the genus Haemulon.
AB  - During this study (December 2009 to December 2010), underwater visual surveys
      using the focal animal method were performed in the coastal reefs of Tamandare,
      north-eastern Brazil. The aim was to analyse the effects of the life phase
      (juvenile and adult) and schooling patterns (school and solitary) on the feeding
      behaviour (foraging rates and substratum preferences) of four species of the
      genus Haemulon (Haemulon aurolineatum, Haemulon parra, Haemulon plumieri and
      Haemulon squamipinna). PERMANOVA analysis (P < 0.05) indicated that ontogenetic
      changes and schooling patterns directly influence foraging behaviour. Schooling
      individuals had low foraging rates (mean +/- s.d. = 2.3 +/- 2.1 bites 10 min(-1))
      and mobility, usually remaining near the bottom; however, solitary fishes had
      high foraging rates (mean +/- s.d. = 12.5 +/- 4.6 bites 10 min(-1)). Juveniles
      preferred feeding in the water column (75% of the total number of bites), whereas
      adults foraged mainly in sand (80%) and bare rock (20%). All four Haemulon
      species displayed similar patterns of feeding behaviour as well as preferences
      for foraging sites and display competition for food resources. In contrast,
      little is known about their habitat use and foraging behaviour over the diel
      cycle, particularly the newly settled and early juvenile stages.

PMID- 23557302
TI  - Marginal increment analysis: a new statistical approach of testing for temporal
      periodicity in fish age verification.
AB  - This paper proposes a new and flexible statistical method for marginal increment
      analysis that directly accounts for periodicity in circular data using a circular
      linear regression model with random effects. The method is applied to vertebral
      marginal increment data for Alaska skate Bathyraja parmifera. The best fit model
      selected using the AIC indicates that growth bands are formed annually.
      Simulation, where the underlying characteristics of the data are known, shows
      that the method performs satisfactorily when uncertainty is not extremely high.

PMID- 23557303
TI  - Effects of a muscle-infecting parasitic nematode on the locomotor performance of
      their fish host.
AB  - The southern flounder Paralichthys lethostigma, host to the nematode
      Philometroides paralichthydis that is embedded in place of the inclinator muscles
      of the dorsal and anal fin elements, is hypothesized to impair two aspects of
      locomotor performance (swimming and burying capacity). Peak swimming acceleration
      and both measures of burying performance did not differ between infected and
      uninfected fish, whereas swimming velocity of infected fish was significantly
      lower than that of uninfected fish. Smaller infected fish swam at significantly
      slower speeds than smaller uninfected fish, whereas there was no difference among
      larger fish. Neither the location nor the number of worms affected either
      swimming or burying performance. The decrease in swimming velocity observed in
      smaller infected fish may be sufficient in rendering them more vulnerable to
      predation and environmental stressors.

PMID- 23557304
TI  - Hemiodus iratapuru, a new species of Hemiodontidae from the Rio Jari, Amazon
      Basin, Brazil (Teleostei, Characiformes).
AB  - Hemiodus iratapuru, a new species of the Hemiodontidae from the Rio Iratapuru, a
      left bank tributary of the Rio Jari, Amazon Basin, Brazil, is described. The new
      species is diagnosed from other species of Hemiodus by modifications in the
      ectopterygoid, tooth form, scale counts, dorsal-fin form and colour pattern. The
      new species is proposed to be related to the Hemiodus quadrimaculatus species
      group.

PMID- 23557305
TI  - Effects of body mass and water temperature on routine metabolism of American
      paddlefish Polyodon spathula.
AB  - This study quantified the effects of temperature and fish mass on routine
      metabolism of the American paddlefish Polyodon spathula. Thermal sensitivity, as
      measured by Q(10) value, was low in P. spathula. Mean Q(10) was 1.78 while
      poikilotherms are generally expected to have Q(10) values in the 2.00-2.50 range.
      Mass-specific metabolism did not decrease with increased fish size to the extent
      that this phenomenon is observed in teleosts, as evidenced by a mass exponent
      (beta) value of 0.92 for P. spathula compared with 0.79 in a review of teleost
      species. Other Acipenseriformes have exhibited relatively high beta values for
      mass-specific respiration. Overall P. spathula metabolism appears to be more
      dependent on body mass and less dependent on temperature than for many other
      fishes. An equation utilizing temperature and fish mass to estimate gross
      respiration for P. spathula was derived and this equation was applied to
      respiratory data from other Acipenseriformes to assess inter-species variation.
      Polyodon spathula respiration rates across water temperature and fish mass appear
      most similar to those of Atlantic sturgeon Acipenser naccarii and white sturgeon
      Acipenser transmontanus.

PMID- 23557306
TI  - Genetic evaluation of remnant and translocated shiners, Notropis heterodon and
      Notropis heterolepis.
AB  - Population and conservation genetics of two freshwater fish species, Notropis
      heterodon and Notropis heterolepis, were evaluated in north-eastern Illinois,
      U.S.A., where both species have severely declined. Fishes were sampled from two
      remnant populations occurring in small glacial lakes (source samples) and from
      two man-made ponds that had been stocked with fishes from those same lakes
      (sanctuary samples). The goal was to obtain information that would help inform
      conservation programme planning to reintroduce sanctuary fishes to areas where
      both species are extirpated. Microsatellite data showed that the two species were
      genetically quite distinct and there was no evidence of hybridization in either
      source or sanctuary samples. Within each species, source and sanctuary samples
      had moderate levels of heterozygosity and were not significantly different from
      each other. Many alleles observed in the source samples, however, were not
      detected in the sanctuary samples, indicating that translocation had resulted in
      reduced allelic diversity of the sanctuary samples. Sibship analysis indicated
      that full and half sibs occurred within source-lake samples, thus reducing the
      effective population size of the reintroduced stock. Taken together, these
      results suggest that source-lake stocks rather than sanctuary stocks are more
      appropriate for future reintroductions of both species in their native range,
      unless sanctuary populations can be established with hundreds of fishes. Also,
      fishes should be harvested from multiple locations in source lakes to avoid over
      representation of family groups.

PMID- 23557307
TI  - Trophic shift in young-of-the-year Mugilidae during salt-marsh colonization.
AB  - This study investigated the trophic shift of young-of-the-year (YOY) thinlip grey
      mullet Liza ramada and golden grey mullet Liza aurata during their recruitment in
      a salt marsh located on the European Atlantic Ocean coast. Stable-isotope
      signatures (delta(13) C and delta(15) N) of the fishes followed a pattern, having
      enrichments in (13) C and (15) N with increasing fork length (LF ): delta(13) C
      in fishes < 30 mm ranged from -19.5 to -15.00/00, whereas in fishes > 30 mm
      delta(13) C ranged from -15.8 to -12.70/00, closer to the level in salt-marsh
      food resources. Large differences between the delta(15) N values of mugilids and
      those of food sources (6.00/00 on average) showed that YOY are secondary
      consumers, similar to older individuals, when feeding in the salt marsh. YOY
      mugilids shift from browsing on pelagic prey to grazing on benthic resources from
      the salt marsh before reaching 30 mm LF. The results highlight the role of
      European salt marshes as nurseries for juvenile mugilids.

PMID- 23557308
TI  - Head-shape polymorphism in Japanese eels Anguilla japonica in relation to
      differences of somatic growth in freshwater and brackish habitats.
AB  - The age, total length (L(T)), head shape and skull shape were investigated for
      379 Japanese eels Anguilla japonica sampled in freshwater and brackish areas of
      the Kojima Bay-Asahi River system, Okayama, Japan, to learn about the
      differentiation process of head-shape polymorphism. The relative mouth width
      (ratio of mouth width to L(T)) of A. japonica > 400 mm L(T) collected in fresh
      water was significantly greater than that of fish collected in brackish water.
      Growth rates of mouth width and the distance from the snout to the midpoint of
      the eyes (the ratio of width and distance to age, respectively) were not
      significantly different between freshwater and brackish-water samples, whereas
      the somatic growth rate (the ratio of L(T) to age) of freshwater samples was
      significantly lower than that of brackish-water eel samples. These results
      suggest that the factors affecting head and somatic growth of A. japonica are not
      identical. According to these results and feeding patterns in each habitat
      reported by another study, it is suggested that somatic growth appears to play a
      significant role in the differentiation process of the head-shape polymorphism in
      A. japonica, with the slow-growing fish in fresh water becoming broad-headed and
      the fast-growing fish in brackish water becoming narrow-headed.

PMID- 23557309
TI  - Comparative morphology of the sagittal otolith in three species of south Caspian
      gobies.
AB  - Sagittal otolith shapes were investigated in order to identify three sympatric
      species of south Caspian gobies (Caspian goby Neogobius caspius, deepwater goby
      Ponticola bathybius and bighead goby Ponticola gorlap). The sagittal otoliths in
      P. bathybius have a rectangular shape and are thick, whereas in N. caspius they
      are relatively round and thin. In P. gorlap, otoliths have an elongated shape and
      are relatively thick. The noticeable difference among the otoliths of the three
      species is the presence of one anterior and one posterior projection in the
      otoliths of N. caspius and P. gorlap. Among shape indices, form factor
      (irregularity of surface area), circularity, aspect ratio and rectangularity are
      the foremost that indicate interspecific variability. The canonical discriminant
      analysis correctly classifies 94.7% of the original group cases. The overall
      analyses show the relevance of applying otolith shape for interspecific
      distinction of the three species of Caspian gobies.

PMID- 23557310
TI  - Reproductive biology of squaretail coralgrouper Plectropomus areolatus using age
      based techniques.
AB  - The squaretail coralgrouper Plectropomus areolatus was identified as a fast
      growing, early maturing and relatively short-lived aggregation-spawning
      epinephelid. Examinations of sectioned otoliths found females and males first
      maturing at 2 and 3 years, respectively, suggesting protogynous hermaphroditism;
      however, no transitionals were observed in samples. Age distribution for the two
      sexes was similar and both were represented in the oldest age class; however,
      significant sex-specific differences in size-at-age were identified. Both sexes
      fully recruit into the fishery at age 4 years and reach 90% of asymptotic length
      by age 3 years. Underwater visual assessments, combined with the gonado-somatic
      indices, revealed a 5 month reproductive season, with interannual variability
      observed in the month of highest density within the spawning aggregation. Catch
      restrictions on adults during spawning times and at reproductive sites, combined
      with gear-based management and enhanced enforcement, are recommended to maintain
      spawning stocks. Based on the available evidence, the sexual pattern for this
      species is unresolved.

PMID- 23557311
TI  - A revision of the Lower Guinean Hepsetus species (Characiformes; Hepsetidae) with
      the description of Hepsetus kingsleyae sp. nov.
AB  - An alpha-taxonomic revision of the African pike, Hepsetus odoe, from Lower Guinea
      is provided. The results show that three different species occur in Lower Guinea
      instead of one. Hepsetus akawo, recently described from West Africa, is present
      in the northern part of Lower Guinea; Hepsetus lineata, the most widespread
      species within Lower Guinea, is known from the Sanaga (Cameroon) in the north to
      the Shiloango (Democratic Republic of the Congo) in the south and Hepsetus
      kingsleyae sp. nov. is endemic to the Ogowe Basin. The new species H. kingsleyae
      is described and H. lineata, which is elevated here to the species level, is
      redescribed. Hepsetus lineata can easily be recognized by its prominent
      horizontal line pattern on the flanks and differs further from H. akawo and H.
      kingsleyae in the number of lateral-line scales and the number of gill rakers.
      Hepsetus kingsleyae differs from H. lineata and H. akawo by its narrow head,
      elongated snout and narrow, knife-shaped body. All three species are also
      distinguishable from H. odoe and the recently revalidated H. cuvieri. A few
      exceptional specimens could not be allocated to one of the three species and may
      represent hybrids because of their mixed diagnostic characters or their
      intermediate values.

PMID- 23557312
TI  - Moon phase influences the diet of southern Ray's bream Brama australis.
AB  - Diet composition of the southern Ray's bream Brama australis was examined from
      stomach contents of 399 specimens sampled by bottom trawl on Chatham Rise to the
      east of South Island, New Zealand, over 3 years. Prey items were predominantly
      mesopelagic fishes and crustaceans. Multivariate analysis indicated that moon
      phase explained more of the diet variability than any other predictor examined.
      It appears likely that diet composition is influenced by a combination of changes
      in both tidal flows and illumination. Different combinations of prey were
      consumed by B. australis at different times of the lunar cycle. An influence of
      moon phase on feeding by fishes has rarely been reported, but it is likely that
      moon phase influences the diets of other species that specialize in mesopelagic
      prey. The most important prey group by mass for B. australis was Myctophidae
      (primarily Lampanyctodes hectoris), followed by Stomiiformes (primarily
      Maurolicus australis) and shrimps (Sergestes spp). An ontogenetic shift in diet
      was observed, from numerical dominance by small crustaceans including amphipods
      and euphausiids (with some fishes) in smaller (mass <1045 g) B. australis to
      pelagic teleost prey (with a few larger crustaceans) in larger (>1440 g) B.
      australis.

PMID- 23557313
TI  - Chemosensory cues attract lake trout Salvelinus namaycush and an egg predator to
      the spawning substratum.
AB  - A field experiment was conducted to determine whether chemosensory cues emanating
      from lake trout Salvelinus namaycush spawning substratum attract breeding S.
      namaycush. Substrata from either a spawning site or a control site were randomly
      placed in trap nets around an isolated spawning shoal; those containing spawning
      substratum caught significantly more S. namaycush, as well as a greater
      proportion in breeding condition. White sucker Catostomus commersoni were a major
      predator of S. namaycush eggs and were also captured in greater numbers in nets
      with spawning substratum.

PMID- 23557314
TI  - Short-term dynamics of nest occupancy in an allopaternal species, the tessellated
      darter Etheostoma olmstedi.
AB  - To inquire how male size interacts with alloparental behaviour and mating success
      in the tessellated darter Etheostoma olmstedi, males were given a choice of nests
      with or without eggs; subsequent nest occupancy, takeovers and egg deposits were
      monitored. Subordinate males readily occupied available nests with eggs but were
      often evicted by dominant males, suggesting that males of all sizes compete for
      the opportunity to provide allopaternal care in this species.

PMID- 23557315
TI  - Haematological response of curimbas Prochilodus lineatus, naturally infected with
      Neoechinorhynchus curemai.
AB  - This study evaluated the haematological response of curimbas Prochilodus
      lineatus, naturally infected with Neoechinorhynchus curemai (Acanthocephala:
      Neoechinorhynchidae). Thirty-seven fish were captured in October 2010 from the
      Mogi Guacu River, Porto Ferreira, SP, Brazil. Infected fish presented increased
      mean corpuscular volume of erythrocytes, and lower thrombocyte and higher
      monocyte counts than uninfected fish.

PMID- 23557316
TI  - Can sea trout Salmo trutta compromise successful eradication of Gyrodactylus
      salaris by hiding from CFT Legumin (rotenone) treatments?
AB  - In this study, 34 anadromous brown trout (sea trout) Salmo trutta were equipped
      with acoustic transmitters in order to examine whether they performed avoidance
      behaviour in response to a CFT Legumin (rotenone) treatment in the Norwegian
      River Vefsna. Migratory behaviour of the S. trutta was monitored by use of 15
      automatic listening stations and manual tracking in the lower part of the river,
      in the estuary and in the fjord. None of the studied S. trutta survived the
      rotenone treatment and no indications of successful avoidance behaviour were
      observed.

PMID- 23557317
TI  - First record of dicephalia in a bull shark Carcharhinus leucas (Chondrichthyes:
      Carcharhinidae) foetus from the Gulf of Mexico, U.S.A.
AB  - The first recorded incidence of dicephalia in a bull shark Carcharhinus leucas is
      reported from a foetus collected by a fisherman in the Gulf of Mexico near
      Florida, U.S.A. External examination, Radiography and magnetic resonance imaging
      revealed a case of monosomic dicephalia where the axial skeleton and internal
      organs were found to divide into parallel systems anterior to the pectoral girdle
      resulting in two well-developed heads.

PMID- 23557318
TI  - Shifts in delta15 N signature following the onset of exogenous feeding in rainbow
      trout Oncorhynchus mykiss: importance of combining length and age data.
AB  - The delta(15) N isotopic change of recently emerged rainbow trout Oncorhynchus
      mykiss due to diet shift from yolk sac to exogenous feeding was evaluated in a
      field study. The fit of a general model including both fish length and age in
      days as co-variables indicates that the specific delta(15) N of individual fish
      at any given time along the ontogeny is determined by its growth trajectory. The
      results suggest that estimations based on fish size alone could bias data
      interpretation and maternal origin determinations in partially migratory
      salmonids.

PMID- 23557319
TI  - The first confirmed cases of full albinism in rajid species.
AB  - Three albino skate specimens (Rajidae) were captured from the North Sea and
      English Channel between 2008 and 2011. Using DNA barcoding (COI gene) and
      morphometric analyses, species were identified as a spotted ray Raja montagui, a
      blonde ray Raja brachyura and a thornback ray Raja clavata. This finding
      represents the first record of full albinism (a lack of skin and retinal
      pigmentation) in rajid species.

PMID- 23557320
TI  - Neuropeptide Y in black seabream Acanthopagrus schlegelii: identification,
      distribution and mRNA expression responses to ghrelin.
AB  - The coding region of neuropeptide Y (NPY) complementary (c)DNA was cloned from
      the hypothalamus RNA of black seabream Acanthopagrus schlegelii, including 297 bp
      coding for prepro-NPY of 98 amino acids. Real-time reverse transcriptase
      polymerase chain reaction was performed to determine A. schlegelii npy gene
      expression; NPY messenger RNA (mRNA) was expressed highly in the brain and
      stomach. Treatment with acylated ghrelin significantly up-regulated NPY mRNA
      level in the hypothalamus, suggesting that NPY may be involved in regulating food
      intake of A. schlegelii.

PMID- 23557321
TI  - Using formative research to design a context-specific behaviour change strategy
      to improve infant and young child feeding practices and nutrition in Nepal.
AB  - Global recommendations on strategies to improve infant feeding, care and
      nutrition are clear; however, there is limited literature that explains methods
      for tailoring these recommendations to the local context where programmes are
      implemented. This paper aims to: (1) highlight the individual, cultural and
      environmental factors revealed by formative research to affect infant and young
      child feeding and care practices in Baitadi district of Far Western Nepal; and
      (2) outline how both quantitative and qualitative research methods were used to
      design a context-specific behaviour change strategy to improve child nutrition.
      Quantitative data on 750 children aged 12-23 months and their families were
      collected via surveys administered to mothers. The participants were selected
      using a multistage cluster sampling technique. The survey asked about knowledge,
      attitude and behaviours relating to infant and young child feeding. Qualitative
      data on breastfeeding and complementary feeding beliefs and practices were also
      collected from a separate sample via focus group discussions with mothers, and
      key informant interviews with mothers-in-law and husbands. Key findings revealed
      gaps in knowledge among many informants resulting in suboptimal infant and young
      child feeding practices - particularly with relation to duration of exclusive
      breastfeeding and dietary diversity of complementary foods. The findings from
      this research were then incorporated into a context-specific nutrition behaviour
      change communication strategy. 

PMID- 23557322
TI  - Effectiveness of intravitreal ranibizumab in exudative age-related macular
      degeneration (AMD): comparison between typical neovascular AMD and polypoidal
      choroidal vasculopathy over a 1 year follow-up.
AB  - BACKGROUND: The effects of intravitreal ranibizumab (IVR) against exudative age
      related macular degeneration (AMD) may be different associated with the lesion
      phenotype. This study was conducted to compare the outcomes of IVR between two
      different phenotypes of exudative AMD: typical neovascular AMD (tAMD) and
      polypoidal choroidal vasculopathy (PCV). METHODS: This is a retrospective cohort
      study of 54 eyes from 54 subfoveal exudative AMD patients (tAMD 24, PCV 30 eyes).
      Three consecutive IVR treatments (0.5 mg) were performed every month, followed by
      re-injections as needed. Change in the best-corrected visual acuity (BCVA) and
      central retinal thickness (CRT) were then compared between the tAMD and PCV
      groups over 12 months of follow-up. RESULTS: The mean BCVA was significantly
      improved (-0.11 logMAR units) at month 3 after the initial IVR (p <0 .001,
      Wilcoxon signed-rank test), and was sustained up to 12 months in all AMD patients
      (p =0.02). In the subgroup analysis, the tAMD group showed a significant
      improvement in their mean BCVA (-0.06, -0.17, -0.15 and -0.16 logMAR units at 1,
      3, 6 and 12 months, respectively), but there was only a slight but non
      significant improvement in the PCV group. The improvement in the BCVA was
      significantly greater in the tAMD group than in the PCV group (p = 0.043,
      repeated measures ANOVA) over 12 months. Both phenotypes showed significant
      improvements in the CRT during 12 months after the initial IVR. CONCLUSIONS: IVR
      is an effective therapy for tAMD and PCV in the BCVA improvement in Japanese
      patients over 12 months of follow-up. The phenotype of tAMD showed a
      significantly better outcome with IVR than PCV in terms of BCVA improvement.

PMID- 23557323
TI  - A pilot study of an exercise & cognitive behavioral therapy intervention for
      epithelial ovarian cancer patients.
AB  - BACKGROUND: Ovarian cancer has the highest mortality rate of all gynaecologic
      cancers. Faced with poor prognoses, stressful treatment effects and a high
      likelihood of recurrence, survivors must confront significant physical and
      psychological morbidities that negatively impact health-related quality of life.
      Frequently reported side effects include cancer-related fatigue, peripheral
      neuropathy, and psychological distress. Exercise and cognitive behavioral therapy
      interventions have counteracted such adverse effects in other cancer populations.
      OBJECTIVE: To investigate the feasibility and benefits of a 24-week home-based
      exercise intervention, coordinated with 12 weeks of cognitive behavioral therapy
      (two sessions per month), developed for two types of patients diagnosed with
      epithelial ovarian cancer: 1) those undergoing primary treatment with adjuvant
      chemotherapy after primary surgery; 2) those on surveillance after completing
      treatment within the last 2 years. METHODS: Participants were recruited from the
      Gynaecologic Oncology Clinic. Eligible participants completed baseline
      assessments and were provided with home-based exercise equipment. Cognitive
      behavioral therapy was provided every other week for patients via telephone.
      Assessments were completed at baseline (T1), 3 months (T2) and 6 months (T3).
      RESULTS: 19 of the 46 eligible patients approached were enrolled, with 7 patients
      in the treatment group and 12 in the surveillance group. There was a significant
      within group increase in peak VO2 from baseline to 6 months: F(2,16) = 5.531, p =
      0.015, partial eta2 = 0.409. CONCLUSION: The combined 6-month exercise-cognitive
      behavioral therapy intervention was associated with significant increases in
      aerobic fitness in epithelial ovarian cancer patients assessed. These
      improvements were similar regardless of whether the patient was receiving
      chemotherapy or under surveillance.

PMID- 23557324
TI  - Quality assurance: recommended guidelines for safe heating by capacitive-type
      heating technique to treat patients with metallic implants.
AB  - This article is a redissemination of the previous Japanese Quality Assurance
      Guide guidelines. Specific absorption rate and temperature distribution were
      investigated with respect to various aspects including metallic implant size and
      shape, insertion site, insertion direction, blood flow and heating power, and
      simulated results were compared with adverse reactions of patients treated by
      radio frequency capacitive-type heating. Recommended guidelines for safe heating
      methods for patients with metallic implants are presented based on our findings.

PMID- 23557325
TI  - Lithography-free fabrication of silicon nanowire and nanohole arrays by metal
      assisted chemical etching.
AB  - We demonstrated a novel, simple, and low-cost method to fabricate silicon
      nanowire (SiNW) arrays and silicon nanohole (SiNH) arrays based on thin silver
      (Ag) film dewetting process combined with metal-assisted chemical etching. Ag
      mesh with holes and semispherical Ag nanoparticles can be prepared by simple
      thermal annealing of Ag thin film on a silicon substrate. Both the diameter and
      the distribution of mesh holes as well as the nanoparticles can be manipulated by
      the film thickness and the annealing temperature. The silicon underneath Ag
      coverage was etched off with the catalysis of metal in an aqueous solution
      containing HF and an oxidant, which form silicon nanostructures (either SiNW or
      SiNH arrays). The morphologies of the corresponding etched SiNW and SiNH arrays
      matched well with that of Ag holes and nanoparticles. This novel method allows
      lithography-free fabrication of the SiNW and SiNH arrays with control of the size
      and distribution.

PMID- 23557326
TI  - Ebstein's anomaly with subpulmonary obstruction--a rare association.
AB  - Ebstein's anomaly comprises a wide spectrum of congenital cardiac abnormalities
      involving the tricuspid valve (TV) apparatus and the architecture of the
      morphological right ventricle (RV). We report a case of Ebstein's anomaly in a 3
      year-old boy having a unique association with severe subpulmonic obstruction
      caused by tethered and dysplastic anterior tricuspid leaflet (ATL), and a large
      ventricular septal defect. In view of poorly functioning RV, the baby was planned
      for a bidirectional Glenn shunt with subsequent Fontan completion. 

PMID- 23557327
TI  - Effects of BRAF inhibitors on human melanoma tissue before treatment, early
      during treatment, and on progression.
AB  - Selective BRAF inhibitors (BRAFi) are a standard of care for the treatment of
      BRAF(V) (600) -mutant metastatic melanoma. We analyzed a unique set of serial
      triplicate human metastatic melanoma tumor biopsies to identify biomarkers of
      BRAFi response and resistance. Morphologic features and immunohistochemical
      biomarkers were analyzed in 37 metastatic melanoma biopsies at pretreatment
      (PRE), early during treatment (EDT), and on progression (PROG) from 15 patients
      treated with a BRAFi and correlated with response and outcome. At EDT,
      proliferative markers decreased regardless of response, whereas markers of cell
      death increased in responders. High expression of nuclear p27 at baseline was the
      strongest predictor of a poorer OS and predicted worse response. The results show
      that BRAFi are universally antiproliferative, regardless of clinical response,
      whereas markers of cell death increased only in responders. The addition of
      therapies targeting the cell cycle machinery may improve the response and
      duration of BRAFi, and investigation of the mechanisms of apoptosis may provide
      additional therapeutic targets. 

PMID- 23557328
TI  - Mimiviridae: clusters of orthologous genes, reconstruction of gene repertoire
      evolution and proposed expansion of the giant virus family.
AB  - BACKGROUND: The family Mimiviridae belongs to the large monophyletic group of
      Nucleo-Cytoplasmic Large DNA Viruses (NCLDV; proposed order Megavirales) and
      encompasses giant viruses infecting amoeba and probably other unicellular
      eukaryotes. The recent discovery of the Cafeteria roenbergensis virus (CroV), a
      distant relative of the prototype mimiviruses, led to a substantial expansion of
      the genetic variance within the family Mimiviridae. In the light of these
      findings, a reassessment of the relationships between the mimiviruses and other
      NCLDV and reconstruction of the evolution of giant virus genomes emerge as
      interesting and timely goals. RESULTS: Database searches for the protein
      sequences encoded in the genomes of several viruses originally classified as
      members of the family Phycodnaviridae, in particular Organic Lake phycodnaviruses
      and Phaeocystis globosa viruses (OLPG), revealed a greater number of highly
      similar homologs in members of the Mimiviridae than in phycodnaviruses. We
      constructed a collection of 898 Clusters of Orthologous Genes for the putative
      expanded family Mimiviridae (MimiCOGs) and used these clusters for a
      comprehensive phylogenetic analysis of the genes that are conserved in most of
      the NCLDV. The topologies of the phylogenetic trees for these conserved viral
      genes strongly support the monophyly of the OLPG and the mimiviruses. The same
      tree topology was obtained by analysis of the phyletic patterns of conserved
      viral genes. We further employed the mimiCOGs to obtain a maximum likelihood
      reconstruction of the history of genes losses and gains among the giant viruses.
      The results reveal massive gene gain in the mimivirus branch and modest gene gain
      in the OLPG branch. CONCLUSIONS: These phylogenomic results reported here suggest
      a substantial expansion of the family Mimiviridae. The proposed expanded family
      encompasses a greater diversity of viruses including a group of viruses with much
      smaller genomes than those of the original members of the Mimiviridae. If the
      OLPG group is included in an expanded family Mimiviridae, it becomes the only
      family of giant viruses currently shown to host virophages. The mimiCOGs are
      expected to become a key resource for phylogenomics of giant viruses.

PMID- 23557330
TI  - Clinical significance of CD163+ tumor-associated macrophages in patients with
      adult T-cell leukemia/lymphoma.
AB  - In several malignant tumors including lymphoma, macrophages that infiltrate tumor
      tissues are called tumor-associated macrophages (TAMs). We discovered that TAMs,
      especially the CD163+ alternatively activated phenotype (M2), were closely
      involved with progression of adult T-cell leukemia/lymphoma (ATLL). We used CD68
      (a pan-macrophage marker) and CD163 (an M2 marker) to immunostain 58 ATLL
      samples. Statistical analyses showed that a high number of CD68+ TAMs and an
      increased percentage of CD163+ cells among the TAMs were associated with a worse
      clinical prognosis; multivariate analysis indicated that the percentage of CD163+
      cells was an independent prognostic factor. We also carried out in vitro
      coculture experiments with ATLL cell lines (ATN-1 and TL-Mor) and monocyte
      derived macrophages and found that direct coculture with M2 macrophages
      significantly increased BrdU incorporation into ATLL cell lines. A cytokine array
      analysis showed that macrophage-derived soluble factors including C5a, tumor
      necrosis factor-alpha, growth-related oncogene-alpha, CCL1/I-309, and interleukin
      6 stimulated ATLL cell lines. CD163 expression in macrophages was strongly
      induced by direct contact with ATN-1 cells, and downregulation of CD163 in
      macrophages significantly suppressed growth of cocultured ATN-1 cells. These
      results suggest that interaction between M2 macrophages and lymphoma cells may be
      an appropriate target in treatment of patients with ATLL.

PMID- 23557329
TI  - Identification of microRNA-mRNA functional interactions in UVB-induced senescence
      of human diploid fibroblasts.
AB  - BACKGROUND: Cellular senescence can be induced by a variety of extrinsic stimuli,
      and sustained exposure to sunlight is a key factor in photoaging of the skin.
      Accordingly, irradiation of skin fibroblasts by UVB light triggers cellular
      senescence, which is thought to contribute to extrinsic skin aging, although
      molecular mechanisms are incompletely understood. Here, we addressed molecular
      mechanisms underlying UVB induced senescence of human diploid fibroblasts.
      RESULTS: We observed a parallel activation of the p53/p21(WAF1) and
      p16(INK4a)/pRb pathways. Using genome-wide transcriptome analysis, we identified
      a transcriptional signature of UVB-induced senescence that was conserved in three
      independent strains of human diploid fibroblasts (HDF) from skin. In parallel, a
      comprehensive screen for microRNAs regulated during UVB-induced senescence was
      performed which identified five microRNAs that are significantly regulated during
      the process. Bioinformatic analysis of miRNA-mRNA networks was performed to
      identify new functional mRNA targets with high confidence for miR-15a, miR-20a,
      miR-20b, miR-93, and miR-101. Already known targets of these miRNAs were
      identified in each case, validating the approach. Several new targets were
      identified for all of these miRNAs, with the potential to provide new insight in
      the process of UVB-induced senescence at a genome-wide level. Subsequent analysis
      was focused on miR-101 and its putative target gene Ezh2. We confirmed that Ezh2
      is regulated by miR-101 in human fibroblasts, and found that both overexpression
      of miR-101 and downregulation of Ezh2 independently induce senescence in the
      absence of UVB irradiation. However, the downregulation of miR-101 was not
      sufficient to block the phenotype of UVB-induced senescence, suggesting that
      other UVB-induced processes induce the senescence response in a pathway redundant
      with upregulation of miR-101. CONCLUSION: We performed a comprehensive screen for
      UVB-regulated microRNAs in human diploid fibroblasts, and identified a network of
      miRNA-mRNA interactions mediating UVB-induced senescence. In addition, miR-101
      and Ezh2 were identified as key players in UVB-induced senescence of HDF.

PMID- 23557331
TI  - Text-messaging versus telephone reminders to reduce missed appointments in an
      academic primary care clinic: a randomized controlled trial.
AB  - BACKGROUND: Telephone or text-message reminders have been shown to significantly
      reduce the rate of missed appointments in different medical settings. Since text
      messaging is less resource-demanding, we tested the hypothesis that text-message
      reminders would be as effective as telephone reminders in an academic primary
      care clinic. METHODS: A randomized controlled non-inferiority trial was conducted
      in the academic primary care division of the Geneva University Hospitals between
      November 2010 and April 2011. Patients registered for an appointment at the
      clinic, and for whom a cell phone number was available, were randomly selected to
      receive a text-message or a telephone call reminder 24 hours before the planned
      appointment. Patients were included each time they had an appointment. The main
      outcome was the rate of unexplained missed appointments. Appointments were not
      missed if they were cancelled or re-scheduled before or independently from the
      intervention. We defined non-inferiority as a difference below 2% in the rate of
      missed appointments and powered the study accordingly. A satisfaction survey was
      conducted among a random sample of 900 patients (response rate 41%). RESULTS:
      6450 patients were included, 3285 in the text-message group and 3165 in the
      telephone group. The rate of missed appointments was similar in the text-message
      group (11.7%, 95% CI: 10.6-12.8) and in the telephone group (10.2%, 95% CI: 9.2
      11.3 p = 0.07). However, only text message reminders were cost-effective. No
      patient reported any disturbance by any type of reminder in the satisfaction
      survey. Three quarters of surveyed patients recommended its regular
      implementation in the clinic. CONCLUSIONS: Text-message reminders are equivalent
      to telephone reminders in reducing the proportion of missed appointments in an
      academic primary care clinic and are more cost-effective. Both types of reminders
      are well accepted by patients.

PMID- 23557332
TI  - Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to
      galsulfase.
AB  - BACKGROUND: Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome; MPS VI) is an
      autosomal recessive lysosomal storage disorder in which deficiency of N
      acetylgalactosamine 4-sulfatase (arylsulfatase B; ARSB) leads to the storage of
      glycosaminoglycans (GAGs) in connective tissue. The genotype-phenotype
      correlation has been addressed in several publications but the picture is not
      complete. Since 2007, enzyme-replacement therapy (ERT) has been available for
      patients with MPS VI in the Netherlands. The purpose of our study was to learn
      more about the genotype-phenotype correlations in MPS VI and the antibody
      response to ERT with galsulfase (recombinant human arylsulfatase B). METHODS: We
      identified ARSB mutations in 12 patients and used site-directed mutagenesis to
      study their effect. Antibody levels to galsulfase were measured using ELISA and a
      semi-quantitative immunoprecipitation method. We assessed the in vitro inhibitory
      effect of antibodies on galsulfase uptake and their effect on clinical outcome.
      RESULTS: Five patients had a rapidly progressive phenotype and seven a slowly
      progressive phenotype. In total 9 pathogenic mutations were identified including
      4 novel mutations (N301K, V332G, A237D, and c.1142 + 2 T > C) together composing
      8 pathogenic genotypes. Most mutations appeared not to affect the synthesis of
      ARSB (66 kD precursor), but to hamper its maturation (43 kD ARSB). Disease
      severity was correlated with urinary GAG excretion. All patients developed
      antibodies to galsulfase within 26 weeks of treatment. It was demonstrated that
      these antibodies can inhibit the uptake of galsulfase in vitro. CONCLUSIONS: The
      clinical phenotypes and the observed defects in the biosynthesis of ARSB show
      that some of the mutations that we identified are clearly more severe than
      others. Patients receiving galsulfase as enzyme-replacement therapy can develop
      antibodies towards the therapeutic protein. Though most titers are modest, they
      can exceed a level at which they potentially affect the clinical outcome of
      enzyme-replacement therapy.

PMID- 23557333
TI  - The nuclear import receptor Kpnbeta1 and its potential as an anticancer
      therapeutic target.
AB  - Many proteins require transport across the nuclear envelope, the physical barrier
      separating the nucleus from the cytoplasm. Karyopherin beta (Kpnbeta1) proteins
      are the major nuclear receptor proteins in the cell that cargo proteins across
      the nuclear envelope, allowing them to enter and exit the cell nucleus.
      Karyopherin beta1, a major nuclear import receptor, plays an integral role in
      importing transcription factors, cell signaling proteins, cell cycle proteins,
      and so forth, into the nucleus, thus playing a crucial role in maintaining normal
      cell homeostasis. However, cancer cells appear to differentially regulate the
      expression of the Karyopherin beta proteins, presumably in order to maintain
      increased nuclear transport rates, thus implicating this protein family as a
      target for cancer therapy. The role of Kpnbeta1 in cancer is only now being
      elucidated, and recent work points to its potential usefulness as an anti-cancer
      target.

PMID- 23557334
TI  - The role of cathepsins in osteoimmunology.
AB  - Cathepsins are proteases comprising two small groups of serine and aspartic
      cathepsins and a large group of lysosomal cysteine cathepsins. Most of them are
      ubiquitously expressed throughout human tissues but some of them display a more
      restricted expression pattern and are involved in explicit tasks such as collagen
      degradation in the process of bone and cartilage destruction or degradation of
      invariant chain peptides in the process of antigen processing and presentation.
      In addition to the aforementioned functions, cathepsins have been shown to play a
      critical role in the pathogenesis of osteoimmunological diseases involving mutual
      interactions between skeletal and immunological functions. The most convincing
      evidence that cathepsins participate in the pathogenesis of osteoimmunological
      disorders exists for cathepsins K and S. Therefore, this review focuses on recent
      advances in understanding the role of cathepsins K and S in osteoimmunology and
      highlights the progress that has been made in targeting cathepsins to treat
      diseases related to the skeletal or immune system.

PMID- 23557335
TI  - Role of cancer-related inflammation in esophageal cancer.
AB  - Esophageal cancer (EC) is the ninth most common malignancy with a poor prognosis.
      It is clear that improvements need to be made to reveal the exact molecular
      mechanisms of EC. Cancer-related inflammation (CRI) recently has been proposed as
      a major physiological hallmark of malignancy and has important value in
      diagnosis, treatment, and prognosis. But the role of CRI in EC has remained
      unclear. In this review, we focus primarily on the function of key mediators of
      CRI in EC, including transcription factors, chemokines, cytokines, reactive
      oxygen species, COX-2, and specific microRNAs. Through a comprehensive analysis,
      we try to reveal the interaction between CRI and EC, providing novel preventive,
      diagnostic, and therapeutic strategies to reduce the health burden of EC.

PMID- 23557336
TI  - The paradoxical role of Nrf2 in tumor biology.
AB  - Nrf2 is used as a cell protector by mediating many downstream genes which express
      phase II detoxifying and antioxidant enzymes. Recently, large numbers of
      experiments have shown Nrf2 and its downstream genes are found to be
      overexpressed in many human tumors. Numerous evidences unveil that Nrf2 protects
      the normal cells while promoting the malignant tumor's progression. The
      paradoxical role of Nrf2 has not been clearly elucidated before. Here, we review
      the suppressor or oncogene roles of Nrf2 in different stages of specific tumors
      with respect to the newest studies. Further, we suspect that the hypoxic
      microenvironment around the tumors is the main crux which determines the role of
      Nrf2 in the tumor initiation, invasion, and metastasis. In the initiation of
      tumors, Nrf2 or Keap1 genes get mutations under the oxidative stress; as a
      result, the tumor cells obtain the advantage to growth. At the later stages, the
      hypoxic microenvironment around the malignant tumors has a profound influence on
      the character of Nrf2. Under the hypoxic microenvironment, expression of certain
      downstream genes of Nrf2 involved in angiogenesis are obviously elevated; other
      transcription factors derived from hypoxic microenvironment interact with Nrf2
      and in that way promote or inhibit the invasion and metastasis.

PMID- 23557337
TI  - Brucella virulence mechanisms and implications in novel vaccines and drugs.
AB  - Brucellosis, an infection caused by Brucella spp., is a common zoonosis in many
      parts of world. Human chronic infection is successfully established through
      contact with infected animals or their dirty products. The capacity of
      establishing and maintaining this persistent infection in the phagosomal
      compartment of host macro-phages is critical to their ability to produce chronic
      infections in their mammalian hosts. Bacterial virulence mechanisms play an
      important role in regulating during the infectious process, both to optimize the
      functioning of the virulence factors in promoting survival and thwarting host
      defenses and to produce an effective immune response against these virulence
      components. The availability of the genomic sequences and molecular strategies
      such as gene mutant technique provide an opportunity to identify the virulence
      mechanisms of Brucella. It will greatly accelerate our understanding of the
      infection of this pathogen and give us more clues to exploit new vaccines and
      drugs.

PMID- 23557338
TI  - Important biology events and pathways in Brucella infection and implications for
      novel antibiotic drug targets.
AB  - Brucellosis caused by Brucella spp. is a common zoonosis in many parts of the
      world. Humans are infected through contact with infected animals or their dirty
      products. Many mechanisms are needed for this successful infection, although the
      mechanisms are still unclear. Host immune response and some signaling molecules
      play an important role in the infection event. Bacterial pathogens operate by
      attacking crucial intracellular pathways or some important molecules in each of
      these pathways for survival in their hosts. The crucial components (molecules) of
      immunity or pathway play a critical role in the whole process of Brucella
      infection. Here we summarize the findings of the Brucella-host interactions'
      immune system and signaling molecular cascades involved in the TLR-initiated
      immune response to Brucella spp. infection. The paper serves to deepen our
      understanding of this complex process and to provide some clues regarding the
      discovery of drug targets for prevention and control.

PMID- 23557339
TI  - Chemokines and chemokine receptors as promoters of prostate cancer growth and
      progression.
AB  - Prostate cancer (CaP) is estimated to be first in incidence among cancers, with
      more than 240,000 new cases in 2012 in the United States. Chemokines and their
      receptors provide survival, proliferation, and invasion characteristics to CaP
      cells in both primary sites of cancer and metastatic locations. The emerging data
      demonstrate that many chemokines and their receptors are involved in the
      multistep process of CaP, leading to metastasis, and, further, that these factors
      act cooperatively to enhance other mechanisms of tumor cell survival, growth, and
      metastasis. Changes of chemokine receptor cohorts may be necessary to activate
      tumor-promoting signals. Chemokine receptors can activate downstream effectors,
      such as mitogen-activated protein kinases, by complex mechanisms of ligand
      dependent activation of cryptic growth factors; guanosine triphosphate-binding,
      protein-coupled activation of survival kinases; or transactivation of other
      receptors such as ErbB family members. We describe vanguard research in which
      more than the classic view of chemokine receptor biology was clarified. Control
      of chemokines and inhibition of their receptor activation may add critical tools
      to reduce tumor growth, especially in chemo-hormonal refractory CaP that is both
      currently incurable and the most aggressive form of the disease, accounting for
      most of the more than 28,000 annual deaths.

PMID- 23557340
TI  - Praxis and writing in a right-hander with crossed aphasia.
AB  - Studies of patients with brain lesions have demonstrated that language and praxis
      are mediated by dissociable networks. However, language has the capacity to
      influence the selection of purposeful actions. The abilities to use language and
      to program purposeful movements are often mediated by networks that have anatomic
      proximity. With hemispheric injury, the diagnosis of apraxia is often confounded
      by the specific influence of language impairments on the ability to select and
      produce transitive gestures. We report a patient who illustrates this confound.
      This patient is a right-handed man who developed global aphasia and neglect after
      a right hemispheric stroke. His right hand remained deft, and when asked to
      produce specific transitive gestures (pantomimes), he often performed normally
      but did make some body part as object and perseverative errors. However, he did
      not demonstrate the temporal or spatial errors typical of ideomotor apraxia. He
      also had a perseverative agraphia. Our patient's left hemisphere praxis system
      appeared to be intact, and the error types demonstrated during production of
      transitive gestures cannot be attributed to a degradation of postural and
      movement (praxis) programs mediated by his left hemisphere. The praxis errors
      types are most consistent with a deficit in the ability to select the necessary
      praxis programs. Thus, our patient appeared to have dissociation between language
      and praxis programs that resulted in body part as object and perseverative
      errors. 

PMID- 23557341
TI  - Langerhans cell sarcoma: a case report and review of the literature.

PMID- 23557342
TI  - Investigation of capsaicin-induced superficial punctate keratopathy model due to
      reduced tear secretion in rats.
AB  - PURPOSE: The present study investigated the usefulness of the superficial
      punctate keratopathy (SPK) model due to reduced tear secretion induced by the
      injection of capsaicin in neonatal rats. METHODS: On postnatal day 4, rats were
      injected subcutaneously with a single dose of capsaicin. Ocular surface symptoms
      were evaluated by measuring corneal sensitivity, tear secretion and corneal
      fluorescein score. Furthermore, the effect of pilocarpine was investigated by
      measuring tear secretion and corneal fluorescein score in this model. The
      influence of discontinuation of pilocarpine application was also examined.
      RESULTS: Capsaicin caused a dose-dependent reduction of tear secretion and
      increase of corneal fluorescein score. In addition, 50 mg/kg capsaicin-treated
      rats showed a sustained decrease of corneal sensitivity and tear secretion, and
      an increase of corneal fluorescein score compared with vehicle-treated rats.
      Moreover, capsaicin-treated rats showed SPK. Instillation of pilocarpine
      significantly increased tear secretion and tended to improve the corneal
      fluorescein score by repeated application, whereas tear secretion and corneal
      fluorescein score in the pilocarpine-treated rats returned to the same level as
      that of capsaicin-treated rats after discontinuation of pilocarpine application.
      CONCLUSIONS: Injection of capsaicin in rats induced stable SPK due to reduced
      tear secretion accompanied by a decrease of corneal sensitivity. Thus, it may be
      concluded that this model is essentially similar to SPK due to reduced tear
      secretion and could be used in the development of appropriate new drugs for
      therapy.

PMID- 23557343
TI  - Exceptional thermal stability of Pd@CeO2 core-shell catalyst nanostructures
      grafted onto an oxide surface.
AB  - Monolayer films of highly catalytically active Pd@CeO2 core-shell nanocomposites
      were grafted onto a planar YSZ(100) (yttria-stabilized zirconia, YSZ) single
      crystal support that was functionalized with a CVD-deposited layer of
      triethoxy(octyl)silane (TEOOS). The resulting monolayer films were found to
      exhibit exceptionally high thermal stability compared to bare Pd nanoparticles
      with the Pd@CeO2 nanostructures remaining intact and highly dispersed upon
      calcining in air at temperatures in excess of 1000 K. The CeO2 shells were also
      shown to be more easily reduced than bulk CeO2, which may partially explain their
      unique activity as oxidation catalysts. The use of both TEOOS and
      tetradecylphosphonic acid (TDPA) as coupling agents for dispersing Pd@CeO2 core
      shell nanocomposites onto a high surface area gamma-Al2O3 support is also
      demonstrated.

PMID- 23557344
TI  - Repositioning patients in chairs-an improved method.
AB  - Proper seated posture is important in health care settings because immobilized
      patients may be sitting for extended periods. In many situations, a caregiver is
      required to assist a slouching patient to a proper, more comfortable upright
      posture. The caregiver is at risk from exposure to the physical demands of this
      task. This study evaluated exertion and risk to the caregiver using three methods
      of repositioning patients in chairs in the health care setting. Through
      application of a new method employing an ergonomically designed device, exertion
      and risk were reduced. Results from this study indicate that the high-risk
      occupational activity of repositioning a slouching patient in a chair can be made
      safer for caregivers.

PMID- 23557345
TI  - Actual cardiovascular disease risk and related factors: a cross-sectional study
      of Korean blue collar workers employed by small businesses.
AB  - Actual cardiovascular disease (CVD) risk and related factors among blue collar
      workers employed by small businesses were investigated. This cross-sectional
      study of 238 Korean blue collar workers used surveys, anthropometric and blood
      pressure measurements, and blood sampling for lipid and glucose levels to answer
      the research questions. Multiple regression techniques were used to analyze study
      data. The prevalence of actual CVD risk among blue collar workers was 32 cases
      per 100 workers. A multiple regression model showed that a combination of
      individual, psychosocial, and work-related factors explained 34% of the variance
      in actual CVD risk. The significant predictors of actual CVD risk included
      knowledge of CVD risk, risk perception, job stress, and waist-to-hip ratio. It is
      important for clinicians to consider all of these significant predictors of
      actual CVD risk when designing an intervention program to reduce CVD among Korean
      blue collar workers.

PMID- 23557346
TI  - Evaluating and improving nurses' health and quality of work life.
AB  - This article discusses evaluating and improving the health and quality of work
      life (QOWL) of nurses. Nurses are reported to have higher illness, disability,
      and absenteeism rates than all other health care workers. Research suggests that
      QOWL impacts nurses' health and the provision of quality health care,
      particularly patient safety. Occupational health nurses have a pivotal role in
      evaluating and improving nurses' QOWL and health. This will ensure quality health
      outcomes for nurses and patients and reduce costs for the health care system.

PMID- 23557348
TI  - Selecting health-related apps.
AB  - Although many apps exist, occupational and environmental health nurses should
      only recommend apps that deliver credible content and safeguard user data.

PMID- 23557349
TI  - Novel ceruloplasmin mutation causing aceruloplasminemia with hepatic iron
      overload and diabetes without neurological symptoms.

PMID- 23557350
TI  - Antioxidant activity of various solvent fractions from edible brown alga, Eisenia
      bicyclis and its active compounds.
AB  - In this study, we aimed to elucidate the antioxidant capacity of Eisenia bicyclis
      and evaluated its antioxidant activity using various assay systems such as 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azino-bis (3
      ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, reducing power
      ability, and content of total polyphenol. Among all the performed experiments,
      the ethyl acetate fraction of E. bicyclis exhibited higher antioxidant
      activities. From this finding, isolation and purification were performed on the
      ethyl acetate fraction and identified dieckol and phlorofucofureoeckol-A by
      spectroscopic analyses including FAB-mass in the negative mode, (1) H NMR, (13) C
      NMR, (1) H-(1) H COSY, HMQC, and HMBC spectra. Interestingly, ABTS radical
      scavenging activities of dieckol and phlorofucofuroeckol showed strong effects of
      65.36% and 70.38% at a concentration of 50 MUg/mL, respectively. DPPH radical
      scavenging and reducing power abilities were increased in a dose-dependent manner
      at various concentrations. These results suggest that dieckol and
      phlorofucofuroeckol-A of E. bicyclis may play an important role in protection
      from oxidative stress involving reactive oxygen species and may contribute to the
      development of new bio products, for example, a useful preservative to improve
      food quality and a drug for various oxidative damage-associated diseases.
      Practical Application: The results suggest that dieckol and phlorofucofuroeckol-A
      can be utilized as a natural source for potential application of antioxidant in
      food industry and drug for oxidative damage-associated diseases.

PMID- 23557351
TI  - Making use of expertise: a qualitative analysis of the experience of
      breastfeeding support for first-time mothers.
AB  - There is now a body of research evaluating breastfeeding interventions and
      exploring mothers' and health professionals' views on effective and ineffective
      breastfeeding support. However, this literature leaves relatively unexplored a
      number of questions about how breastfeeding women experience and make sense of
      their relationships with those trained to provide breastfeeding support. The
      present study collected qualitative data from 22 breastfeeding first-time mothers
      in the United Kingdom on their experiences of, and orientation towards,
      relationships with maternity care professionals and other breastfeeding advisors.
      The data were obtained from interviews and audio-diaries at two time points
      during the first 5 weeks post-partum. We discuss a key theme within the data of
      'Making use of expertise' and three subthemes that capture the way in which the
      women's orientation towards those assumed to have breastfeeding expertise varied
      according to whether the women (1) adopted a position of consulting experts vs.
      one of deferring to feeding authorities; (2) experienced difficulty interpreting
      their own and their baby's bodies; and (3) experienced the expertise of health
      workers as empowering or disempowering. Although sometimes mothers felt empowered
      by aligning themselves with the scientific approach and 'normalising gaze' of
      health care professionals, at other times this gaze could be experienced as
      objectifying and diminishing. The merits and limitations of a person-centred
      approach to breastfeeding support are discussed in relation to using
      breastfeeding expertise in an empowering rather than disempowering way. 

PMID- 23557352
TI  - Drug use profile in outpatient children and adolescents in different Italian
      regions.
AB  - BACKGROUND: Large differences exist in the prevalence rate of drugs prescribed to
      children and adolescents between and within countries. The aim of this study was
      to evaluate child and adolescent drug prescription patterns in Italy in an extra
      hospital setting at the regional and Local Health Unit (LHU) levels. METHODS:
      Data sources were three regional prescription databases. Data concerning the year
      2008 were evaluated. A total of 3.3 million children and adolescents were
      included. Drug prevalence and prescription rates were evaluated at the regional
      and LHU levels. The correlation between mean latitude, average annual income,
      hospitalisation rate, number of paediatricians per 1,000 resident children, and
      prevalence rate was evaluated by LHU using a linear multiple regression analysis.
      RESULTS: Large differences were found across Italian regions and LHUs. The mean
      prevalence rate was 56.4% (95% CI 56.3-56.5%; 51.2-65.4% among regions) and, at
      the LHU level, ranged from 43.1% to 70.0% (higher in the South). A total of 878
      drugs were prescribed, 175 of which were shared by all LHUs. Amoxicillin
      clavulanate was the most used drug in all regions and in 31 of 33 LHUs.
      Amoxicillin was the drug with the highest variability in use between LHUs (9.1
      52.1% of treated children). An inverse correlation was found between prevalence
      rate and both latitude (p < 0.0001) and average annual income (p = 0.0002).
      CONCLUSIONS: The use of drugs in children and adolescents is higher in southern
      Italy and is inversely related to latitude and average annual income. More
      efforts should be devoted to informing physicians, patients and policy makers in
      order to plan effective initiatives to improve the situation.

PMID- 23557353
TI  - Draft genome of Ochrobactrum intermedium strain M86 isolated from non-ulcer
      dyspeptic individual from India.
AB  - BACKGROUND: Ochrobactrum intermedium is an emerging opportunistic pathogen of
      humans that is closely related to members of the genus Brucella. Earlier, we
      reported the case of an Indian subject with non-ulcer dyspeptic symptoms whose
      urease positive gastric biopsy revealed the presence of Helicobacter pylori along
      with non-Helicobacter like bacteria, eventually cultured and identified as O.
      intermedium strain M86. RESULTS: Here, we describe the unclosed draft genome of
      the strain M86 with a length of 5,188,688 bp and mean G+C content of 57.9%. We
      have also identified many putative gene clusters that might be responsible for
      its persistence in the gastric mucosa.Comparative analysis of genomic features of
      Ochrobactrum intermedium strain M86 and Ochrobactrum intermedium LMG 3301T was
      also done. CONCLUSIONS: This paper attempts to gain whole-genome based insights
      into the putative gene determinants of O. intermedium for survival in the highly
      acidic stomach lumen environment .Identification of genes putatively involved in
      the various metabolic pathways may lead to a better understanding of the survival
      of O. intermdedium in acidic condition.

PMID- 23557354
TI  - Potential tumor biomarkers identified in ovarian cyst fluid by quantitative
      proteomic analysis, iTRAQ.
AB  - BACKGROUND: Epithelial-derived ovarian adenocarcinoma (EOC) is the most deadly
      gynecologic tumor, and the principle cause of the poor survival rate is diagnosis
      at a late stage. Screening and diagnostic biomarkers with acceptable specificity
      and sensitivity are lacking. Ovarian cyst fluid should harbor early ovarian
      cancer biomarkers because of its closeness to the tumor. We investigated ovarian
      cyst fluid as a source for discovering biomarkers for use in the diagnosis of
      EOC. RESULTS: Using quantitative mass spectrometry, iTRAQ MS, we identified 837
      proteins in cyst fluid from benign, EOC stage I, and EOC stage III. Only patients
      of serous histology were included in the study. Comparing the benign (n = 5) with
      the malignant (n = 10) group, 87 of the proteins were significantly (p < 0.05)
      differentially expressed. Two proteins, serum amyloid A-4 (SAA4) and astacin-like
      metalloendopeptidase (ASTL), were selected for verification of the iTRAQ method
      and external validation with immunoblot in a larger cohort with mixed histology,
      in plasma (n = 68), and cyst fluid (n = 68). The protein selections were based on
      either high significance and high fold change or abundant appearance and several
      peptide recognitions in the sample sets (p = 0.04, FC = 1.95) and (p < 0.001, FC
      = 8.48) for SAA4 and ASTL respectively. Both were found to be significantly
      expressed (p < 0.05), but the methods did not correlate concerning ASTL.
      CONCLUSIONS: Fluid from ovarian cysts connected directly to the primary tumor
      harbor many possible new tumor-specific biomarkers. We have identified 87
      differentially expressed proteins and validated two candidates to verify the
      iTRAQ method. However several of the proteins are of interest for validation in a
      larger setting.

PMID- 23557355
TI  - Spermicidal activity of Indian seaweeds: an in vitro study.
AB  - Contraceptive properties of seaweeds are still stands as lacuna; in this context,
      the screening of in vitro male contraceptive properties of crude ethanolic
      extract of Indian seaweeds against normal human sperm is carried out. In total,
      twelve seaweeds were screened for in vitro spermicidal activity. Among these
      twelve seaweeds, Halimeda gracilis showed 100% inhibition of human spermatozoa at
      10 mg ml(-1) concentration in 20 s and its EC50 value was 2.05 mg ml(-1) in 20 s.
      Further, dose- and time-dependent spermicidal assay revealed that the sperm was
      completely immobilised for 20 s. Plasma membrane of sperm was damaged due to the
      exposure of H. gracilis extract. MTT assay with H. gracilis extract showed 88.5%
      of cytotoxic incidence. H. gracilis extract tested for cytotoxicity against
      Artemia salina recorded LC50 value of 34.8 MUg ml(-1) . Phytochemical analysis of
      H. gracilis extract evidenced the presence of alkaloids, flavonoids, proteins and
      sugars. Results of this study clearly inferred that the synergistic effect of
      active principles reside within the H. gracilis extract had shown better
      contraceptive activity. 

PMID- 23557356
TI  - ASD device embolization: caught in the act.

PMID- 23557357
TI  - Dynamic evolving two-component supramolecular gels-hierarchical control over
      component selection in complex mixtures.
AB  - We report a two-component acid-amine gelation system which forms instant
      organogels on simple mixing. We investigate self-assembly using a wide range of
      different amines and identify the optimum amines for gelation to occur. Using NMR
      and other spectroscopic methods, we unambiguously determine the stoichiometry of
      the complex responsible for gelation (1:1) and characterize the noncovalent
      interactions responsible for gelation. Using Kamlet-Taft parameters we gain a
      detailed understanding of the role of solvent on gelation. Most importantly, we
      explore the ability of these multicomponent systems to assemble from complex
      mixtures, and using NMR can determine which components are preferentially taken
      up into the immobile "solid-like" fiber network and which components remain
      mobile in the "liquid-like" solvent phase. In this way, we determine that the
      component selection process is controlled by the two key steps in hierarchical
      assembly: (i) acid-base complex formation (as predicted by the pKa of the amine)
      and (ii) gel fiber assembly (as predicted by the Tgel value). These parameters
      therefore enable a predictive understanding of the way in which complex mixtures
      self-organize and assemble and also how the sorted assemblies disassemble on
      heating. In a key experiment, we demonstrate that these materials are highly
      responsive and that a preformed gel, exposed to a new component, evolves, adapts,
      and heals its composition in response to the thermodynamic preferences of the
      overall system.

PMID- 23557358
TI  - Chk1 is essential for the development of murine epidermal melanocytes.
AB  - Embryonic deletion of mouse Chk1 is lethal; however, whether Chk1 is essential in
      all individual tissues is unknown. By breeding C57Bl/ 6 mice homozygous for a
      conditional allele of Chk1 (Chk1fl/fl) and bearing melanocyte-specific Tyr::Cre
      and DCT:: LacZ transgenes, we investigated the consequences of Chk1 deletion in
      the melanocytic lineage. We show that adult Tyr::Cre; Chk1fl/fl mice lack coat
      pigmentation and epidermal melanocytes in the hair follicles, but retain eye
      pigmentation in the retinal pigmented epithelium (RPE). Melanoblasts formed
      normally during embryogenesis in Tyr::Cre; Chk1fl/fl mice at early times
      (embryonic day 10.5; E10.5) but were completely absent by stage E13.5, most
      probably as a consequence of spontaneous DNA damage and apoptosis. By contrast,
      melanoblast numbers were only slightly reduced in heterozygous Tyr::Cre; Chk1fl/
      + embryos, and these mice exhibited normal coat pigmentation as adults. Thus,
      Chk1 is essential for the developmental formation of murine epidermal melanocytes
      but hemizygosity has little, if any, permanent developmental consequence in this
      cell type. 

PMID- 23557359
TI  - Synthetic immunotherapy induces HIV virus specific Th1 cytotoxic response and
      death of an HIV-1 infected human cell line through classic complement activation.
AB  - BACKGROUND: This manuscript describes the development of a novel synthetic
      immunotherapy (HIV-v) composed of four multi-epitope polypeptides targeting
      conserved regions in the Nef, Rev, Vif and Vpr viral proteins. Immunogenicity and
      cytotoxicity of HIV-v are discussed. METHODS: Short conserved T-cell multi
      epitope regions were identified in silico in the HIV proteome. The immunogenicity
      of the identified HIV-v polypeptides was assessed in vivo by immunisation of
      C57BLK6 mice transgenic for HLA-A*0201. Splenocytes from immunised animals were
      exposed in vitro to soluble HIV-v polypeptides or to syngeneic (T1) or allogeneic
      (Jurkat) cells transfected with these polypeptides. Specific T-cell reactivity
      was assessed by cell-based IFN-gamma ELISA. Virus specific CD3 + CD8+ IFN-gamma+
      recall responses were also determined by flow cytometry following in vitro
      exposure of splenocytes from immunised mice to syngeneic (T1) and allogeneic (H9)
      cells infected with HIV-1 strain IIIB. HIV-v specific antibodies were quantified
      by ELISA whilst antibody mediated anti-viral immunotherapeutic effect on T1 cells
      infected with a laboratory adapted and a primary isolate of the HIV-1 virus was
      assessed in a LDH-based complement mediated lysis assay. RESULTS: HIV-v elicited
      antigen-specific IgG and IFN-gamma responses against the synthetic polypeptides
      in the formulation. HIV-v specific T cells recognised polypeptides presented
      either as soluble antigen or complexed to HLA-A*0201 following natural processing
      and presentation by syngeneic human T1 cells. Moreover, the CD3 + CD8+ component
      of the response recognised syngeneic T1 cells naturally infected with HIV-1 in a
      virus-specific and MHC restricted-manner. The HIV-v specific IgG response was
      also able to recognise human T1 cells naturally infected with HIV-1 and induce
      cell death through classic activation of complement. CONCLUSIONS: HIV-v induces a
      vaccine-specific type I immune response characterised by activation of effector
      CD8+ T cell and antibody responses that recognise and kill human cell lines
      naturally infected with a laboratory adapted and a primary isolate of the HIV-1
      virus. The data supports the hypothesis that alternative HIV protein targets can
      be effectively used to prime both cellular and antibody immune responses of
      clinical value in the prevention and treatment of HIV infection.

PMID- 23557361
TI  - Contraceptive social marketing in Albania - the NESMARK story.
AB  - OBJECTIVES: To present the history of social marketing of modern contraceptives
      in Albania. METHODS: We review documentation and activity of NESMARK, an Albanian
      non-governmental social marketing organisation, and national data on adoption of
      modern contraception. RESULTS: During 15 years of awareness raising, sales of
      affordable products, and provider training, NESMARK has impacted the introduction
      and adoption of modern contraception in Albania. NESMARK is the country's main
      distributor of emergency contraception (EC) and complements the public sector in
      the distribution of condoms and oral contraceptives. NESMARK has made major
      efforts to overcome prevalent taboos and misinformation held by medical and
      nursing personnel, pharmacists and the general public, regarding the
      effectiveness and safety of condoms, oral contraceptives, and EC. CONCLUSIONS:
      NESMARK has contributed to increasing the choices for modern contraception
      methods in Albania by providing affordable contraceptives, training providers,
      and educating the general population. However, widespread use of withdrawal
      coupled with the belief that it is as or more effective than modern
      contraception, continues to limit uptake of new methods and is a significant
      challenge to comprehensive and sustained social marketing programmes.

PMID- 23557360
TI  - High-throughput genome sequencing of lichenizing fungi to assess gene loss in the
      ammonium transporter/ammonia permease gene family.
AB  - BACKGROUND: Horizontal gene transfer has shaped the evolution of the ammonium
      transporter/ammonia permease gene family. Horizontal transfers of ammonium
      transporter/ammonia permease genes into the fungi include one transfer from
      archaea to the filamentous ascomycetes associated with the adaptive radiation of
      the leotiomyceta. The horizontally transferred gene has subsequently been lost in
      most of the group but has been selectively retained in lichenizing fungi.
      However, some groups of lichens appear to have secondarily lost the archaeal
      ammonium transporter. Definitive assessment of gene loss can only be made via
      whole genome sequencing. RESULTS: Ammonium transporter/ammonia permease gene
      sequences were recovered from the assembled genomes of eight lichenizing fungi in
      key clades including the Caliciales, the Peltigerales, the Ostropomycetidae, the
      Acarosporomycetidae, the Verrucariales, the Arthoniomycetidae and the Lichinales.
      The genes recovered were included in a refined phylogenetic analysis. The
      hypothesis that lichens symbiotic with a nitrogen-fixing cyanobacterium as a
      primary photobiont or lichens living in high nitrogen environments lose the plant
      like ammonium transporters was upheld, but did not account for additional losses
      of ammonium transporters/ammonia permeases in the lichens from the
      Acarosporomycetidae, Chaetotheriomycetes and Arthoniomycetes. In addition, the
      four ammonium transporter/ammonia permease genes from Cladonia grayi were shown
      to be functional by expressing the lichen genes in a strain of Saccharomyces
      cerevisiae in which all three native ammonium transporters were deleted, and
      assaying for growth on limiting ammonia as a sole nitrogen source. CONCLUSIONS:
      Given sufficient coverage, next-generation sequencing technology can definitively
      address the loss of a gene in a genome when using environmental DNA isolated from
      lichen thalli collected from their natural habitats. Lichen-forming fungi have
      been losing ammonium transporters/ammonia permease genes at a slower rate than
      the most closely related non-lichenized lineages. These horizontally transferred
      genes in the Cladonia grayi genome encode functional ammonium
      transporters/ammonia permeases.

PMID- 23557362
TI  - Effective treatment of malignant atrophic papulosis (Kohlmeier-Degos disease)
      with treprostinil--early experience.
AB  - BACKGROUND: Malignant atrophic papulosis (Kohlmeier-Degos disease; MAP) is an
      uncommon endotheliopathy with pathological findings similar to the vascular
      lesions of systemic sclerosis. These two disorders can overlap. When associated
      with visceral lesions, MAP has been considered almost universally and rapidly
      fatal. A recent report described dramatic response to treatment with eculizumab,
      but disease progression after initial response to therapy has occurred. METHODS:
      We describe the clinical and pathologic findings in two patients, one with MAP
      and the other with MAP like lesions, who received treatment with subcutaneous
      treprostinil. One patient had an overlap syndrome with features of systemic lupus
      erythematosus (SLE) and scleroderma and severe pulmonary hypertension. She also
      had very extensive MAP like cutaneous lesions. There was no evidence of central
      nervous system (CNS) disease and laparoscopy revealed no visible MAP lesions on
      the serosa of the small bowel. The second patient had experienced life
      threatening disease progression despite ongoing eculizumab therapy. During this
      treatment, he had developed CNS and bladder involvement with neurologic symptoms
      and gross hematuria. RESULTS: Patient one was placed on therapy with treprostinil
      for her pulmonary hypertension, but in the months subsequent to initiation of
      treatment, dramatic and complete resolution of cutaneous MAP like lesions and
      disabling digital pain occurred. In patient two, therapy with treprostinil was
      temporally associated with clearing of hematuria, resolution of CNS symptoms and
      improvement in MRI findings. CONCLUSIONS: Treprostinil may offer a second
      effective treatment approach to individuals with MAP or "rescue therapy" to those
      in whom eculizumab treatment has failed to maintain suppression of disease
      activity.

PMID- 23557363
TI  - Consumers' intention to use health recommendation systems to receive personalized
      nutrition advice.
AB  - BACKGROUND: Sophisticated recommendation systems are used more and more in the
      health sector to assist consumers in healthy decision making. In this study we
      investigate consumers' evaluation of hypothetical health recommendation systems
      that provide personalized nutrition advice. We examine consumers' intention to
      use such a health recommendation system as a function of options related to the
      underlying system (e.g. the type of company that generates the advice) as well as
      intermediaries (e.g. general practitioner) that might assist in using the system.
      We further explore if the effect of both the system and intermediaries on
      intention to use a health recommendation system are mediated by consumers'
      perceived effort, privacy risk, usefulness and enjoyment. METHODS: 204
      respondents from a consumer panel in the Netherlands participated. The data were
      collected by means of a questionnaire. Each respondent evaluated three
      hypothetical health recommendation systems on validated multi-scale measures of
      effort, privacy risk, usefulness, enjoyment and intention to use the system. To
      test the hypothesized relationships we used regression analyses. RESULTS: We find
      evidence that the options related to the underlying system as well as the
      intermediaries involved influence consumers' intention to use such a health
      recommendation system and that these effects are mediated by perceptions of
      effort, privacy risk, usefulness and enjoyment. Also, we find that consumers
      value usefulness of a system more and enjoyment less when a general practitioner
      advices them to use a health recommendation system than if they use it out of
      their own curiosity. CONCLUSIONS: We developed and tested a model of consumers'
      intention to use a health recommendation system. We found that intermediaries
      play an important role in how consumers evaluate such a system over and above
      options of the underlying system that is used to generate the recommendation.
      Also, health-related information services seem to rely on endorsement by the
      medical sector. This has considerable implications for the distribution as well
      as the communication channels of health recommendation systems which may be quite
      difficult to put into practice outside traditional health service channels.

PMID- 23557364
TI  - Analysis of the titer and reactivity of antibody/ies against fungal cell wall
      beta-glucans in human sera.
AB  - The aim of this work was to characterize an antibody response to beta-glucan
      (BG), a major component of the fungal cell wall, at each isotype in human sera.
      The titer and reactivity of the anti-human BG antibody were examined using enzyme
      linked immunosorbant assay plates coated with Candida soluble cell wall beta
      glucan as a standard antigen. The antibody was detected using anti-human
      immunoglobulin (Ig) G, IgM, and IgA. Its major class was IgG in all subjects. The
      antibody titer varied significantly. The anti-BG antibody showed greater
      reactivity to beta-glucans derived from pathogenic fungi than monoglycosyl
      branched beta-glucans derived from mycelia culture medium. In addition, it was
      suggested that the anti-BG IgM antibody was bound relatively strongly to the
      beta1,3-glucan backbone and the anti-BG IgG antibody to beta1,6-glucan. The anti
      BG antibody plays a variety of roles, according to class, in the host's response
      to fungi. We propose a new index of human response to beta-glucan that effects
      the understanding of the response to beta-glucan in humans.

PMID- 23557365
TI  - Probing Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher
      Basidiomycetes): a bitter mushroom with amazing health benefits.
AB  - Ganoderma lucidum (Lingzhi or Reishi) is known as a bitter mushroom with
      remarkable health benefits. The active constituents found in mushrooms include
      polysaccharides, dietary fibers, oligosaccharides, triterpenoids, peptides and
      proteins, alcohols and phenols, mineral elements (such as zinc, copper, iodine,
      selenium, and iron), vitamins, and amino acids. The bioactive components found in
      the G. lucidum mushroom have numerous health properties to treat diseased
      conditions such as hepatopathy, chronic hepatitis, nephritis, hypertension,
      hyperlipemia, arthritis, neurasthenia, insomnia, bronchitis, asthma, gastric
      ulcers, atherosclerosis, leukopenia, diabetes, anorexia, and cancer. In spite of
      the voluminous literature available, G. lucidum is used mostly as an immune
      enhancer and a health supplement, not therapeutically. This review discusses the
      therapeutic potential of G. luidum to attract the scientific community to
      consider its therapeutic application where it can be worth pursuing.

PMID- 23557366
TI  - Purification and characterization of a novel small-molecule polysaccharide from
      the Maitake medicinal mushroom Grifola frondosa (higher Basidiomycetes).
AB  - A novel small-molecule polysaccharide with a molecular mass of 2.6 kDa, was
      isolated from the culinary-medicinal Maitake mushroom Grifola frondosa. GFPS is
      composed of fucose, rhamnose, galactose, glucose, and mannose; galactose,
      glucose, and mannose were the dominant monosaccharides. Absorption peaks at 1077
      cm-1, 1024 cm-1, and 873 cm-1, as revealed by infrared spectrum, suggesting that
      GFPS consists of pyranoside. GFPS significantly enhanced the production of nitric
      oxide and secretion of cytokines (tumor necrosis factor-alpha, interleukin-1beta,
      and interleukin-delta) from macrophages in vitro. These results indicate that
      this novel small-molecule polysaccharide might be beneficial for immune defense.

PMID- 23557367
TI  - Submerged cultivation of mycelium with high ergothioneine content from the
      culinary-medicinal king oyster mushroom Pleurotus eryngii (higher Basidiomycetes)
      and its composition.
AB  - The culinary-medicinal king oyster mushroom, Pleurotus eryngii, was used to
      produce mycelia with high ergothioneine content using a one-factor-at-a-time
      method. The optimal culture conditions for mycelia harvested at day 14 were 25
      degrees C, 10% inoculation rate, 2% glucose, 0.5% yeast extract, and no
      adjustment to the initial pH value. With histidine or amino acid mix added,
      biomasses and the ergothioneine content of mycelia were higher than those of the
      control. The ergothioneine content of mycelia harvested at days 16-20 were higher
      than that of mycelia harvested at day 14. In addition, the ergothioneine content
      of mycelia from the fermentor (5.84-5.76 mg/g) was much higher than that of
      mycelia from the shaken flask (4.93-5.04 mg/g). Mycelia with high ergothioneine
      content showed a profile of proximate composition similar to that of regular
      mycelia but lost its characteristic umami taste. Overall, mycelia high in
      ergothioneine could be prepared by optimal culture conditions, the addition of
      precursors, prolonged harvest, and aeration in the fermentor.

PMID- 23557368
TI  - In vitro anti-Helicobacter pylori effects of medicinal mushroom extracts, with
      special emphasis on the Lion's Mane mushroom, Hericium erinaceus (higher
      Basidiomycetes).
AB  - Although the medicinal mushroom Hericium erinaceus is used extensively in
      traditional Chinese medicine to treat chronic superficial gastritis, the
      underlining pharmaceutical mechanism is yet to be fully understood. In this
      study, minimum inhibitory concentration (MIC) values of extracts prepared from
      the fruiting bodies of 14 mushroom species (H. erinaceus, Ganoderma lucidum,
      Cordyceps militaris, Pleurotus eryngii, P. ostreatus, Agrocybe aegerita, Lentinus
      edodes, Agaricus brasiliensis, A. bisporus, Coprinus comatus, Grifola frondosa,
      Phellinus igniarius, Flammulina velutipes, and Hypsizygus marmoreus) were
      determined against Helicobacter pylori using laboratory strains of ATCC 43504 and
      SS1 as well as 9 clinical isolates via an in vitro microplate agar diffusion
      assay. Ethanol extracts (EEs) of 12 mushrooms inhibited the growth of H. pylori
      in vitro, with MIC values <3 mg/mL. EEs of H. erinaceus and G. lucidum also
      inhibited Staphylococcus aureus (MIC 7360;10 mg/mL) but had no effect on the
      growth of two Escherichia coli test strains (MIC >10 mg/mL). MIC values of ethyl
      acetate fractions (EAFs) of H. erinaceus against 9 clinical isolates of H. pylori
      ranged between 62.5 and 250 ug/mL. The bacteriostatic activity of EAFs was found
      to be concentration-dependant, and the half maximal inhibitory concentration and
      minimum bactericidal concentration values for H. pylori ATCC 43504 were 73.0 and
      200 ug/mL, respectively. The direct inhibitory effect of EEs and EAFs of H.
      erinaceus against H. pylori could be another pharmaceutical mechanism of
      medicinal mushrooms-besides the immunomodulating effect of polysaccharides,
      suggested previously-in the treatment of H. pylori-associated gastrointestinal
      disorders. Further research to identify the active component(s) is currently
      undertaking in our laboratory.

PMID- 23557369
TI  - Production of Ginkgo leaf-shaped basidiocarps of the Lingzhi or Reishi medicinal
      mushroom Ganoderma lucidum (higher Basidiomycetes), containing high levels of
      alpha- and beta-D-glucan and ganoderic acid A.
AB  - Ganoderic acid A and alpha- and beta-D-glucan content were compared among
      morphologically different basidiocarps of the medicinal mushroom Ganoderma
      lucidum. Ginkgo leaf-shaped basidiocarps gradually hardened from the base to the
      pileus and accumulated a higher amount of bioactive components than normal
      (kidney-shaped) and antler/deer horn-shaped basidiocarps. In the normal G.
      lucidum stipe, the outer context contained the highest amount of alpha- and beta
      D-glucan (approximately 55%) and the highest amount of ganoderic acid A
      (approximately 0.3%). Ginkgo leaf-shaped G. lucidum had a large area of outer
      layer and stout outer context, which contributed to their high alpha- and beta-D
      glucan and ganoderic acid A content.

PMID- 23557370
TI  - Production of extracellular polysaccharides by the medicinal mushroom Trametes
      trogii (higher Basidiomycetes) in stirred-tank and airlift reactors.
AB  - Extracellular polysaccharides (EPSs) produced by submerged culture of Trametes
      trogii exhibit antioxidant and antitumor activities. In this study, mycelial
      growth and EPS production of T. trogii were investigated using optimal culture
      conditions (maltose [53.12 g/L] and polypeptone [4.21 g/L] in distilled water) in
      a 5-L jar fermenter. Maximum biomass growth (10.81 g/L) occurred after 5 days of
      cultivation, whereas maximal EPS yield (1.86 g/L) was achieved after 5 days in a
      5-L stirred-tank reactor. Furthermore, the morphological parameters (i.e., mean
      diameter, circularity, roughness, and compactness) of the pellets and the
      viscosity of the broth were characterized. It was proved that the compactness of
      the pellets were significantly positively correlated with EPS content.

PMID- 23557371
TI  - Evaluation of nutraceutical components and antioxidant potential of north Indian
      wild culinary-medicinal Termitophilous mushrooms.
AB  - Mushrooms have long been treated as a delicacy. Nowadays, however, many
      researchers consider them to be nutraceutical foods. The objective of this study
      was to determine the nutraceutical components in 7 edible species of Termitomyces
      (T. microcarpus, T. radicatus, T. badius, T. medius, T. heimii, T. striatus, and
      T. mammiformis) collected from different localities in North India during the
      monsoon season; their antioxidant properties also were determined by DPPH free
      radical scavenging ability and reducing power ability. The various nutraceutical
      components evaluated include phenolics (15.0-25.85 mg/g), flavonoids (1.38-2.02
      mg/g), ascorbic acid (0.018-0.15 mg/g), beta-carotene (0.11-0.27 ug/g), and
      lycopene (0.03-0.19 ug/g).

PMID- 23557372
TI  - Study of the physiological characteristics of the medicinal mushroom Trametes
      pubescens (higher Basidiomycetes) during the laccase-producing process.
AB  - The study of the physiological characteristics of the medicinal mushroom Trametes
      pubescens was conducted under submerged cultures, suggesting that the laccase
      activity was positively correlated with oxidative level and culture conditions.
      Mycelial biomass and laccase activity in medium I were higher than those in
      medium II, which indicated that laccase activity was correlated with mycelium
      growth. The enhancement in mycelial biomass presented the logarithmic increase at
      days 6-8 and the peak value on the day 12 after inoculation. During liquid
      cultivation, increases in the amounts of malondialdehyde, hydrogen peroxide, and
      ascorbic acid were observed. In addition, the higher activities of superoxide
      dismutase and total antioxidative capacity still could be detected during this
      period. However, better ability to restrain hydroxyl free radical and catalase
      had a negative influence on laccase activity. It was evident that the fungal
      strain T. pubescens was under oxidative stress during the laccase-producing
      process. When the concentrations of H2O2 and Fe2+ were 3 and 30 mmol/L,
      respectively, the laccase activity reached to its peak at 37.21 U/L after a 14
      day incubation period. It was concluded that a relationship between laccase
      synthesis and antioxidative capability existed in fungal cells, which could be
      regulated by reactive oxygen.

PMID- 23557373
TI  - Ethnomycological studies of some wild medicinal and edible mushrooms in the
      Kashmir Himalayas (India).
AB  - The medicinal use of mushrooms has a very long tradition in Asian countries
      because of their use as a valuable tonic, food, and in herbal medicines. A study
      was carried out to document the indigenous uses of various mushrooms growing in
      the Kashmir Himalayas. After consulting local herbal healers (Hakims) and people
      from tribal communities inhabiting inaccessible hinterlands of the region
      regarding the use of mushrooms growing in their locality, it was found that 35
      species of mushrooms belonging to different ecological and taxonomical groups
      were used for their nutritional and medicinal values. These mushrooms were used
      for their activities against a broad spectrum of diseases, ranging from simple
      skin diseases to present-day complex diseases such as diabetes and tumors.

PMID- 23557374
TI  - Controlling the alien hand through the mirror box. A single case study of alien
      hand syndrome.
AB  - Disruption of motor control in the alien hand syndrome might result from a
      dissociation between intentions and sensory information. We hypothesized that
      voluntary motor control in this condition could improve by restoring the
      congruency between motor intentions and visual feedback. The present study shows
      that, in one patient with right alien hand syndrome, the use of a mirror box
      paradigm improved motor speed. We speculate that the visual feedback provided by
      the mirror increases the sense of congruence between intention and sensory
      feedback, leading to motor improvement. 

PMID- 23557375
TI  - Kinetics of methane hydrate decomposition studied via in situ low temperature X
      ray powder diffraction.
AB  - Gas hydrate is known to have a slowed decomposition rate at ambient pressure and
      temperatures below the melting point of ice. As hydrate exothermically
      decomposes, gas is released and water of the clathrate cages transforms into ice.
      Based on results from the decomposition of three nominally similar methane
      hydrate samples, the kinetics of two regions, 180-200 and 230-260 K, within the
      overall decomposition range 140-260 K, were studied by in situ low temperature X
      ray powder diffraction. The kinetic rate constants, k(a), and the reaction
      mechanisms, n, for ice formation from methane hydrate were determined by the
      Avrami model within each region, and activation energies, E(a), were determined
      by the Arrhenius plot. E(a) determined from the data for 180-200 K was 42 kJ/mol
      and for 230-260 K was 22 kJ/mol. The higher E(a) in the colder temperature range
      was attributed to a difference in the microstructure of ice between the two
      regions.

PMID- 23557376
TI  - Comparative network-based recovery analysis and proteomic profiling of
      neurological changes in valproic acid-treated mice.
AB  - Despite its prominence for characterization of complex mixtures, LC-MS/MS
      frequently fails to identify many proteins. Network-based analysis methods, based
      on protein-protein interaction networks (PPINs), biological pathways, and protein
      complexes, are useful for recovering non-detected proteins, thereby enhancing
      analytical resolution. However, network-based analysis methods do come in varied
      flavors for which the respective efficacies are largely unknown. We compare the
      recovery performance and functional insights from three distinct instances of
      PPIN-based approaches, viz., Proteomics Expansion Pipeline (PEP), Functional
      Class Scoring (FCS), and Maxlink, in a test scenario of valproic acid (VPA)
      treated mice. We find that the most comprehensive functional insights, as well as
      best non-detected protein recovery performance, are derived from FCS utilizing
      real biological complexes. This outstrips other network-based methods such as
      Maxlink or Proteomics Expansion Pipeline (PEP). From FCS, we identified known
      biological complexes involved in epigenetic modifications, neuronal system
      development, and cytoskeletal rearrangements. This is congruent with the observed
      phenotype where adult mice showed an increase in dendritic branching to allow the
      rewiring of visual cortical circuitry and an improvement in their visual acuity
      when tested behaviorally. In addition, PEP also identified a novel complex,
      comprising YWHAB, NR1, NR2B, ACTB, and TJP1, which is functionally related to the
      observed phenotype. Although our results suggest different network analysis
      methods can produce different results, on the whole, the findings are mutually
      supportive. More critically, the non-overlapping information each provides can
      provide greater holistic understanding of complex phenotypes.

PMID- 23557377
TI  - A rare human-to-human transmission of orf.

PMID- 23557380
TI  - In vitro bactericidal and TEM study of the interaction of Ag-modified titania
      with coliform bacteria.
AB  - This research aimed to investigate in vitro photocatalytic bactericidal effect of
      Ag-TiO2 nanocomposite using Escherichia coli as a model organism. Highly
      dispersed, Ag-TiO2 nanocomposite is used with an average particle size of less
      than 20 nm. Bactericidal analysis was carried out in Luria Bertani medium on
      solid agar plates with various illumination time and different concentrations of
      Ag-TiO2 nanocomposite. Transmission electron microscopic analysis of bacterial
      section was used to detect the effect of irradiation of Ag-TiO2 nanocomposite on
      the ultra structure of the bacterial cell in order to reveal possible cellular
      damage. The mechanism underlying the action of photoexcited Ag-TiO2 nanocomposite
      on E. coli cell membrane is also evaluated. The results confirmed that E. coli
      cells after the contact with Ag-TiO2 nanocomposite were damaged since they showed
      membrane disorganization. This causes the enhanced level of membrane permeability
      leading to the build-up of Ag-TiO2 nanocomposite in the bacterial membrane and
      also cellular internalization of these nanoparticles.

PMID- 23557379
TI  - Enhancement of renal epithelial cell functions through microfluidic-based
      coculture with adipose-derived stem cells.
AB  - Current hemodialysis has functional limitations and is insufficient for renal
      transplantation. The bioartificial tubule device has been developed to contribute
      to metabolic functions by implanting renal epithelial cells into hollow tubes and
      showed a higher survival rate in acute kidney injury patients. In healthy kidney,
      epithelial cells are surrounded by various types of cells that interact with
      extracellular matrices, which are primarily composed of laminin and collagen. The
      current study developed a microfluidic coculture platform to enhance epithelial
      cell function in bioartificial microenvironments with multiple microfluidic
      channels that are microfabricated by polydimethylsiloxane. Collagen gel (CG)
      encapsulated with adipose-derived stem cells (CG-ASC) was injected into a central
      microfluidic channel for three-dimensional (3D) culture. The resuspended Madin
      Darby canine kidney (MDCK) cells were injected into nascent channels and formed
      an epithelial monolayer. In comparison to coculture different cells using the
      commercial transwell system, the current coculture device allowed living cell
      monitoring of both the MDCK epithelial monolayer and CG-ASC in a 3D
      microenvironment. By coculture with CG-ASC, the cell height was increased with
      columnar shapes in MDCK. Promotion of cilia formation and functional expression
      of the ion transport protein in MDCK were also observed in the cocultured
      microfluidic device. When applying fluid flow, the intracellular protein dynamics
      can be monitored in the current platform by using the time-lapse confocal
      microscopy and transfection of GFP-tubulin plasmid in MDCK. Thus, this
      microfluidic coculture device provides the renal epithelial cells with both
      morphological and functional improvements that may avail to develop bioartificial
      renal chips. 

PMID- 23557381
TI  - A three-station DNA catenane rotary motor with controlled directionality.
AB  - The assembly of DNA machines represents a central effort in DNA nanotechnology.
      We report on the first DNA rotor system composed of a two-ring catenane. The DNA
      rotor ring rotates in dictated directions along a wheel, and it occupies three
      distinct sites. Hg(2+)/cysteine or pH (H(+)/OH(-)) act as fuels or antifuels in
      positioning the rotor ring. Analysis of the kinetics reveals directional
      clockwise or anticlockwise population of the target-sites (>85%), and the rotor's
      direction is controlled by the shortest path on the wheel.

PMID- 23557382
TI  - Molecular characterization of Streptococcus agalactiae strains isolated from
      fishes in Malaysia.
AB  - AIMS: The aim of this study was to characterize Streptococcus agalactiae strains
      that were isolated from fishes in Malaysia using random amplified polymorphic DNA
      (RAPD) and repetitive extragenic palindromic PCR (REP-PCR) techniques. METHODS
      AND RESULTS: A total of 181 strains of Strep. agalactiae isolated from red hybrid
      tilapia (Oreochromis sp.) and golden pompano (Trachinotus blochii) were
      characterized using RAPD and REP-PCR techniques. Both the fingerprinting
      techniques generated reproducible band patterns, differing in the number and
      molecular mass amplicons. The RAPD technique displayed greater discriminatory
      power by its production of more complex binding pattern and divided all the
      strains into 13 groups, compared to 9 by REP-PCR technique. Both techniques
      showed the availability to differentiate the genetic profiles of the strains
      according to their geographical location of origin. Three strains of Strep.
      agalactiae that were recovered from golden pompano showed a genetic dissimilarity
      from the strains isolated from red hybrid tilapia, while the strain of ATCC 27956
      that recovered from bovine displayed a unique profile for both methods.
      CONCLUSIONS: Both techniques possess excellent discriminative capabilities and
      can be used as a rapid means of comparing Strep. agalactiae strains for future
      epidemiological investigation. SIGNIFICANCE AND IMPACT OF THE STUDY: Framework as
      the guideline in traceability of this disease and in the search for potential
      local vaccine candidates for streptococcosis in this country.

PMID- 23557383
TI  - Water loss at normal enamel histological points during air drying at room
      temperature.
AB  - This in vitro study aimed to quantify water loss at histological points in ground
      sections of normal enamel during air drying at room temperature (25 degrees C)
      and relative humidity of 50%. From each of 10 ground sections of erupted
      permanent human normal enamel, three histological points (n = 30) located at 100,
      300 and 500 MUm from enamel surface and along a transversal following prisms
      paths were characterized regarding the mineral, organic and water volumes. Water
      loss during air drying was from 0 to 48 h. Drying occurred with both falling and
      constant-drying rates, and drying stabilization times (Teq ) ranged from 0.5 to
      11 h with a mean 0.26 (+/-0.12)% weight loss. In some samples (n = 5; 15 points),
      Teq increased as a function of the distance from the enamel surface, and drying
      occurred at an apparent diffusion rate of 3.47 * 10-8 cm2 s-1. Our data provide
      evidence of air drying resulting in air replacing enamel's loosely bound water in
      prisms sheaths following a unidirectional water diffusion rate of 3.47 * 10-8 cm2
      s-1 (from the original enamel surface inward), not necessarily resulting in water
      evaporating directly into air, with important implications for transport
      processes and optical and mechanical properties.

PMID- 23557378
TI  - Clinical outcomes of patients requiring ventilatory support in Brazilian
      intensive care units: a multicenter, prospective, cohort study.
AB  - INTRODUCTION: Contemporary information on mechanical ventilation (MV) use in
      emerging countries is limited. Moreover, most epidemiological studies on
      ventilatory support were carried out before significant developments, such as
      lung protective ventilation or broader application of non-invasive ventilation
      (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk
      factors for hospital mortality and failure of NIV in patients requiring
      ventilatory support in Brazilian intensive care units (ICU). METHODS: In a
      multicenter, prospective, cohort study, a total of 773 adult patients admitted to
      45 ICUs over a two-month period requiring invasive ventilation or NIV for more
      than 24 hours were evaluated. Causes of ventilatory support, prior chronic health
      status and physiological data were assessed. Multivariate analysis was used to
      identifiy variables associated with hospital mortality and NIV failure. RESULTS:
      Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151
      (20%) patients. Failure with subsequent intubation occurred in 54% of NIV
      patients. The main reasons for ventilatory support were pneumonia (27%),
      neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital
      mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory
      distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital
      mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95%
      confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to
      3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR,
      1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41),
      cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to
      4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67;
      95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were
      independently associated with hospital mortality. The predictors of NIV failure
      were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to
      1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR,
      2.09; 95% CI, 1.02 to 4.30). CONCLUSIONS: Current mortality of ventilated
      patients in Brazil is elevated. Implementation of judicious fluid therapy and a
      watchful use and monitoring of NIV patients are potential targets to improve
      outcomes in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT01268410.

PMID- 23557384
TI  - Of mice, men, and King Tut: autosomal recessive Klippel-Feil syndrome is caused
      by mutations in MEOX1.

PMID- 23557385
TI  - Breastfeeding beliefs and practices of African women living in Brisbane and
      Perth, Australia.
AB  - The purpose of this study was to explore the experience of breastfeeding among
      refugee women from Liberia, Sierra Leone, Burundi and the Democratic Republic of
      Congo living in two major capital cities in Australia. Participants were
      recruited from their relevant community associations and via a snowballing
      technique. Thirty-one women took part in either individual interviews or
      facilitated group discussions to explore their experiences of breastfeeding in
      their home country and in Australia. Thematic analysis revealed four main themes:
      cultural breastfeeding beliefs and practices; stigma and shame around
      breastfeeding in public; ambivalence towards breastfeeding and breastfeeding
      support. Women who originated from these four African countries highlighted a
      significant desire for breastfeeding and an understanding that it was the best
      method for feeding their infants. Their breastfeeding practices in Australia were
      a combination of practices maintained from their countries of origin and those
      adopted according to Australian cultural norms. They exemplified the complexity
      of breastfeeding behaviour and the relationship between infant feeding with
      economic status and the perceived social norms of the host country. The results
      illustrate the need for policy makers and health professionals to take into
      consideration the environmental, social and cultural contexts of the women who
      are purportedly targeted for the promotion of breastfeeding. 

PMID- 23557386
TI  - Hyperglycemia related to high-dose glucocorticoid use in noncritically ill
      patients.
AB  - BACKGROUND: Glucocorticoids commonly cause drug-induced diabetes. This
      association is well recognized but available evidence does not answer clinically
      relevant issues in subjects without diabetes. METHODS: Thirty-five individuals
      without diabetes with a recent diagnosis of acute lymphoblastic leukemia or non
      Hodgkin's lymphoma on high-dose glucocorticoid therapy were studied. Close
      systematic monitoring of fasting and postprandial glycemia and fasting insulin
      determinations, HOMA-insulin resistance and HOMA beta-cell function were
      performed. The primary objective was to define the incidence of secondary
      diabetes in patients treated with high-dose glucocorticoids. Secondary objectives
      were to specify the intensity, the moment it appears and the evolution of
      hyperglycemia, in addition to the risk factors, mechanisms and impact of
      continuous and cyclical glucocorticoids on the development of hyperglycemia.
      RESULTS: Mean age of patients was 38.4 +/- 18.7 years. The incidence of diabetes
      was 40.6% and was found after the first week; half the time it occurred between
      the second and fourth. Two-thirds spontaneously normalized by eight weeks.
      Continuous glucocorticoid administration had a higher incidence of fasting
      hyperglycemia (P = 0.003). Mean peak insulin levels were significantly higher in
      cases of diabetes. CONCLUSIONS: High-dose prednisone for 2 to 3 months produced
      an elevated incidence of diabetes, usually with mild hyperglycemia occurring
      between the second and fourth week, normalizing spontaneously in all cases.
      Hyperglycemia was more frequent with continuous doses and occurred in cases with
      increased insulin resistance. The clinical and therapeutic characteristics of our
      participants, who were otherwise healthy, could represent the clinical setting of
      many patients with illness from other medical areas that might require high doses
      of GC for six to twelve weeks.

PMID- 23557387
TI  - Chemokine (C-C motif) Ligand 2 is a potential biomarker of inflammation &
      physical fitness in obese children: a cross-sectional study.
AB  - BACKGROUND: Obesity is a global epidemic that is impacting children around the
      world. Obesity is a chronic inflammatory state with enhanced production of
      multiple cytokines and chemokines. Chemokine (C-C motif) Ligand 2 (CCL2) is
      produced by immune and metabolic cells and attracts immune cells into liver,
      muscle and adipose tissue, resulting in initiation and propagation of the
      inflammatory response in obesity. How obesity and fitness affect the production
      of this chemokine in children is unknown.This study tested the hypotheses that
      CCL2 levels are higher in obese children when compared to lean controls, and that
      fitness modulates CCL2 levels allowing its use as a biomarker of fitness.
      METHODS: This was a cross sectional case-control study conducted in a Pediatric
      Tertiary care center in Hamilton, Ontario, Canada. Controls were recruited from
      the community. This study recruited overweight/obese children (BMI >= 85th
      percentile, n = 18, 9 female, mean age 14.0 +/- 2.6 years) and lean controls (BMI
      < 85th percentile, n = 18, 8 female, mean age 14.0 +/- 2.6 years) matched for
      age, sex and biological maturation.Aerobic fitness test was done using a cycle
      ergometer performing the McMaster All-Out Progressive Continuous Cycling test to
      exhaustion to determine peak oxygen uptake. Fasting CCL2 samples were taken prior
      to test. Categorical variables including subject categorization into different
      aerobic fitness levels in overweight/obese and lean children was reported based
      on the median split in each group. RESULTS: Obese participants had significantly
      higher CCL2 levels when compared to lean group (150.4 +/- 61.85 pg/ml versus
      112.7 +/- 38 pg/ml, p-value 0.034).To establish if CCL2 is a biomarker of
      fitness, we divided the groups based on their fitness levels. There was a main
      effect for group (F (3,32) = 3.2, p = 0.036). Obese high fitness group were
      similar to lean unfit and fit participants. Post-hoc analysis revealed that the
      overweight/obese low fitness group had significantly higher level of CCL2
      compared to the lean low fitness group when adjusted to age, sex and maturity
      offset (F (3,29) = 3.1, p = 0.04). CONCLUSIONS: CCL2 serves a dual role as a
      potential biomarker of inflammation and fitness in obese children.

PMID- 23557388
TI  - Efficacy and safety of rosuvastatin in late-onset hypogonadism patients with
      dyslipidaemia.
AB  - Rosuvastatin has been used for treatment of dyslipidaemia and metabolic syndrome,
      but the efficacy has not yet been tested in men with late-onset hypogonadism
      (LOH). To assess and compare the efficacy and safety of rosuvastatin in men with
      dyslipidaemia with LOH and non-LOH, a retrospective study was conducted in
      patients who received rosuvastatin 10 mg day(-1) from the men's health clinic.
      The primary endpoint was the change in low-density lipoprotein (LDL)-cholesterol
      (C) after 24 weeks of treatment. A total of 145 dyslipidaemic patients eligible
      for rosuvastatin treatment were enrolled and divided into LOH group (45.52%) and
      non-LOH (54.48%) group. There were favourable changes in the lipid profiles. In
      the LOH group whose serum testosterone had been raised by testosterone
      administration, the favourable changes of the lipids were of similar magnitude as
      in the non-LOH group. The percentage of patients reaching the target goal (LDL <
      100 mg dL(-1) ) did not differ significantly between the group of non-LOH and LOH
      men treated with testosterone. Side effects were noted in 1/145 men. It is
      concluded that rosuvastatin was safe and effective in lowering low-density
      lipoprotein cholesterol in both non-LOH and LOH dyslipidaemic patients whose
      serum testosterone levels had normalised. 

PMID- 23557389
TI  - Imaging cardiac sarcoidosis: the incremental benefit of speckle tracking
      echocardiography.

PMID- 23557390
TI  - Restoration of retinal morphology and residual scarring after photocoagulation.
AB  - PURPOSE: To study healing of retinal laser lesions in patients undergoing PRP
      using SD-OCT. METHODS: Moderate, light and barely visible retinal burns were
      produced in patients with proliferative diabetic retinopathy scheduled for PRP
      using 100-, 20- and 10-ms pulses of 532-nm laser, with retinal spot sizes of 100,
      200 and 400 MUm. Lesions were measured with OCT at 1 hr, 1 week, 1, 2, 4, 6, 9
      and 12 months. OCT imaging was correlated with histology in a separate study in
      rabbits. RESULTS: Lesions produced by the standard 100-ms exposures exhibited
      steady scarring, with the damage zone stabilized after 2 months. For 400- and 200
      MUm spots and 100-ms pulses, the residual scar area at 12 months was
      approximately 50% of the initial lesion size for moderate, light and barely
      visible burns. In contrast, lesions produced by shorter exposures demonstrated
      enhanced restoration of the photoreceptor layer, especially in smaller burns.
      With 20-ms pulses, the damage zone decreased to 32%, 24% and 20% for moderate,
      light and barely visible burns of 400 MUm, respectively, and down to 12% for
      barely visible burns of 200 MUm. In the 100-MUm spots, the residual scar area of
      the moderate 100-ms burns was 41% of the initial lesion, while barely visible 10
      ms burns contracted to 6% of the initial size. Histological observations in
      rabbits were useful for proper interpretation of the damage zone boundaries in
      OCT. CONCLUSIONS: Traditional photocoagulation parameters (400 MUm, 100 ms and
      moderate burn) result in a stable scar similar in size to the beam diameter.
      Restoration of the damaged photoreceptor layer in lighter lesions produced by
      shorter pulses should allow reducing the common side-effects of photocoagulation
      such as scotomata and scarring.

PMID- 23557391
TI  - Integrated materials design of organic semiconductors for field-effect
      transistors.
AB  - The past couple of years have witnessed a remarkable burst in the development of
      organic field-effect transistors (OFETs), with a number of organic semiconductors
      surpassing the benchmark mobility of 10 cm(2)/(V s). In this perspective, we
      highlight some of the major milestones along the way to provide a historical view
      of OFET development, introduce the integrated molecular design concepts and
      process engineering approaches that lead to the current success, and identify the
      challenges ahead to make OFETs applicable in real applications.

PMID- 23557392
TI  - Future physicians and tobacco: an online survey of the habits, beliefs and
      knowledge base of medical students at a Canadian University.
AB  - BACKGROUND: Little is known about the knowledge and attitudes towards tobacco use
      among medical students in Canada. Our objectives were to estimate the prevalence
      of tobacco use among medical students, assess their perceived level of education
      about tobacco addiction management and their preparedness to address tobacco use
      with their future patients. METHODS: A cross-sectional online survey was
      administered to University of Alberta undergraduate medical school trainees. The
      32-question survey addressed student demographics, tobacco use, knowledge and
      attitudes around tobacco and waterpipe smoking, tobacco education received in
      medical school, as well as knowledge and competency regarding tobacco cessation
      interventions. RESULTS: Of 681 polled students, 301 completed the survey. Current
      (defined as "use within the last 30 days") cigarette, cigar/cigarillo and
      waterpipe smoking prevalence was 3.3%, 6% and 6%, respectively. One third of the
      respondents had ever smoked a cigarette, but 41% had tried cigars/cigarillos and
      40% had smoked a waterpipe at some time in the past. Students reported moderate
      levels of education on a variety of tobacco-related subjects but were well
      informed on the role of tobacco in disease causation. The majority of students in
      their final two years of training felt competent to provide tobacco cessation
      interventions, but only 10% definitively agreed that they had received enough
      training in this area. CONCLUSIONS: Waterpipe exposure/current use was
      surprisingly high among this sample of medical students, a population well
      educated about the role of tobacco in disease causation. The majority of
      respondents appeared to be adequately prepared to manage tobacco addiction but
      education could be improved, particularly training in behavioral modification
      techniques used in tobacco use cessation.

PMID- 23557394
TI  - The challenges of the homeless haemophilia patient.
AB  - The current economic hardships within the United States can increase the risk of
      persons becoming homeless. In 2001, it was estimated that between 0.1% and 2.1%
      of the population were homeless every night and that 2.3 - 3.5 million persons
      could become homeless every year [1]. Many issues can increase the risk of
      homelessness including: home foreclosure, declining work force due to declining
      wages, low-wage opportunities and less secure jobs, decline in public assistance,
      lack of affordable housing with limited housing assistance programs, poverty,
      lack of affordable health care, domestic violence, mental illness, and addiction
      disorders. Many on the streets may suffer from mental illness, developmental
      disabilities, and or chronic physical illness [6]. Given these issues, the
      Hemophilia Treatment Center (HTC) can expect to experience the issue of
      homelessness within their own population of persons with hemophilia. Currently,
      there are no studies that address the issue of the person with hemophilia who may
      become homeless. This presents unique challenges that this population may
      encounter to survive in addition to managing bleeding issues related to the
      diagnosis of hemophilia. This article will review the issues related to
      homelessness in the general population. Two case studies of persons with
      hemophilia who became homeless will be discussed outlining the strategies
      utilized to assist the patient during this crisis.

PMID- 23557393
TI  - A C. elegans model to study human metabolic regulation.
AB  - Lipid metabolic disorder is a critical risk factor for metabolic syndrome,
      triggering debilitating diseases like obesity and diabetes. Both obesity and
      diabetes are the epicenter of important medical issues, representing a major
      international public health threat. Accumulation of fat in adipose tissue,
      muscles and liver and/or the defects in their ability to metabolize fatty acids,
      results in insulin resistance. This triggers an early pathogenesis of type 2
      diabetes (T2D). In mammals, lipid metabolism involves several organs, including
      the brain, adipose tissue, muscles, liver, and gut. These organs are part of
      complex homeostatic system and communicate through hormones, neurons and
      metabolites. Our study dissects the importance of mammalian Kruppel-like factors
      in over all energy homeostasis. Factors controlling energy metabolism are
      conserved between mammals and Caenorhabditis elegans providing a new and powerful
      strategy to delineate the molecular pathways that lead to metabolic disorder. The
      C. elegans intestine is our model system where genetics, molecular biology, and
      cell biology are used to identify and understand genes required in fat
      metabolism. Thus far, we have found an important role of C. elegans KLF in FA
      biosynthesis, mitochondrial proliferation, lipid secretion, and beta-oxidation.
      The mechanism by which KLF controls these events in lipid metabolism is unknown.
      We have recently observed that C. elegans KLF-3 selectively acts on insulin
      components to regulate insulin pathway activity. There are many factors that
      control energy homeostasis and defects in this control system are implicated in
      the pathogenesis of human obesity and diabetes. In this review we are discussing
      a role of KLF in human metabolic regulation.

PMID- 23557395
TI  - Treatment of coronary bifurcation lesions: stent-covering of the side branch with
      and without PCI of the side branch: a retrospective analysis of all consecutive
      patients.
AB  - BACKGROUND: Treatment of coronary bifurcation lesions is a complex problem.
      METHODS: This retrospective single-center study included all consecutive patients
      with PCI of coronary bifurcations with stent covering of the side branch (SB)
      between January 2008 - August 2011. RESULTS: Our study group (n = 98) was group A
      (n = 64, 65.3%) and group B (n = 34, 34.7%). Mean follow-up was 14.1 (group A) vs
      12.3 (group B, p = ns) months. CONCLUSION: In patients with coronary bifurcations
      a simpler strategy has a significantly lower MACE. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01538186.

PMID- 23557396
TI  - Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised
      by abundant alveolar accumulation of surfactant lipoproteins. Serum levels of KL
      6, high molecular weight human MUC1 mucin, are increased in the majority of
      patients with PAP. The prognostic significance of KL-6 in PAP is still unknown.
      Aim of the study was to evaluate whether serum KL-6 levels correlate with the
      outcome of the disease. PATIENTS AND METHODS: From 2006 to 2012, we prospectively
      studied 33 patients with primary autoimmune PAP. We measured serum KL-6 levels by
      ELISA (Eisai, Tokyo, Japan), and evaluated the correlation between initial KL-6
      levels and clinical variables. Disease progression was defined as deterioration
      of symptoms, and/or lung function, and/or chest imaging. MAIN RESULTS: The
      initial serum KL-6 levels were significantly correlated with the baseline PaO2, A
      aDO2, DLCO, VC and TLC (p=0.042, 0.012, 0.012, 0.02 and 0.013, respectively). The
      change over time of serum KL-6 correlated with the change over time of DLCO
      (p=0.017). The initial serum KL-6 levels were significantly higher in patients
      with disease progression than in those with remission (p<0.001). At a cut-off
      level of 1526 U/mL, the initial serum KL-6 level predicted disease progression
      (Se 81%, Sp 94%). At a cut-off level of 2157 U/mL, the initial serum KL-6
      predicted the necessity of repeated whole lung lavage (Se 83%, Sp 96%). In the
      multivariate analysis, the initial serum level of KL-6 was the strongest
      predictor of disease progression (HR 9.41, p=0.008). CONCLUSIONS: Serum KL-6
      seems to predict outcome in PAP.

PMID- 23557397
TI  - Do women and providers value the same features of contraceptive products? Results
      of a best-worst stated preference experiment.
AB  - OBJECTIVES: To determine how women and physicians rate individual characteristics
      of contraceptives. METHODS: Discrete choice experiments are used in health
      economics to elicit preferences for healthcare products. A choice experiment uses
      hypothetical scenarios to determine which individual factors influence choice.
      Women and general practitioners (GPs) were shown individual characteristics of
      contraceptives, not always matching existing methods, and chose the best and
      worst features. RESULTS: Two hundred women, mean age 36, 71% using contraception,
      were presented with descriptions of 16 possible methods and asked to indicate
      their preference for individual characteristics. One hundred and sixty-two GPs,
      mostly women, also completed 16 descriptions. Longer duration of action was most
      favoured by both, followed by lighter periods with less pain or amenorrhoea. The
      least attractive features for women were heavier and more painful periods, high
      cost, irregular periods, low efficacy (10% failure) and weight gain of 3 kg. GPs
      ranked a 10% pregnancy rate as least attractive followed by heavy painful periods
      and a 5% failure rate. CONCLUSION: Women and GPs differed in their ranking of
      contraceptive characteristics. Long duration of use, high efficacy, minimal or no
      bleeding without pain, were preferred by both. Very undesirable were heavy
      periods especially with pain, and low efficacy.

PMID- 23557398
TI  - An analysis of splicing, actin-binding properties, heterodimerization and
      molecular interactions of the non-muscle alpha-actinins.
AB  - The non-muscle alpha-actinin isoforms (actinin-1 and -4) are closely related
      dimeric actin filament cross-linking proteins. Despite high sequence similarity,
      unique properties have been ascribed to actinin-4 in particular. For example,
      actinin-4, but not actinin-1, is essential for normal glomerular function in the
      kidney, is overexpressed in several cancers and can translocate to the nucleus to
      regulate transcription. To understand the molecular basis for such isoform
      specific functions we have, for the first time, comprehensively compared these
      proteins in terms of alternative splicing, actin-binding properties, heterodimer
      formation and molecular interactions. We find that the Ca2+-insensitive variant
      of actinin-4 is expressed only in the nervous system and thus cannot be regarded
      as a smooth muscle isoform, as is the case for the Ca2+-insensitive variant of
      actinin-1. The actin-binding properties of actinin-1 and -4 are similar and are
      unlikely to explain isoform-specific functions. Surprisingly, we reveal that
      actinin-1/-4 heterodimers, rather than homodimers, are the most abundant form of
      actinin in many cell lines. Finally, we use a proteomics approach to identify
      potential isoform-specific interactions. The results of the present study
      indicate that actinin-1 and -4 can readily form heterodimers composed of monomers
      that may have different properties and interacting proteins. This significantly
      alters our view of non-muscle actinin function.

PMID- 23557399
TI  - Rydberg states of triatomic hydrogen and deuterium.
AB  - The triatomic hydrogen ion (H3(+)) has spurred tremendous interest in
      astrophysics in recent decades, and Rydberg states of H3 have also maintained an
      important role for understanding H3(+) experiments. In a previous study (J. Chem.
      Phys. 2010, 133, 234302), radiative transitions between neutral H3 Rydberg states
      were calculated at wavelengths near 7 MUm and could be compared with mid-infrared
      laser lines observed in hydrogen/rare gas discharges. The present study extends
      the investigation to wavelengths near 10-13 MUm. Rydberg states of D3 are also
      treated.

PMID- 23557400
TI  - Satisfaction for quality of life: a comparison of patient and occupational
      therapist perspectives.
AB  - OBJECTIVE: To verify whether the patient's satisfaction with quality of life
      (QoL) is similar to or different from the occupational therapist's perception of
      the patient's satisfaction. MATERIALS AND METHODS: Each patient enrolled was
      given the Satisfaction Profile (SAT-P) questionnaire to be filled out personally;
      the same questionnaire, the SAT-P, was given to the respective occupational
      therapist who was asked to fill it out by evaluating the patient's satisfaction
      as perceived by the therapist. A descriptive statistic was applied for socio
      demographic data to describe the cohort. Differences between patient and
      therapist answers to the SAT-P were evaluated using a t-test. RESULTS: 12
      occupational therapists and 69 patients participated in the study. A significant
      difference between occupational therapist and patient was found for Factor II
      (physical functioning) (p = 0.048) and for Factor V (social functioning) (p =
      0.011). The comparison of patient and therapist mean scores showed that
      therapists had a tendency to underestimate patient satisfaction levels for all
      factors except Factor IV. DISCUSSION: The results showed similarities between the
      therapist and the patient's view of the patient's satisfaction with QoL,
      confirming occupational therapy as a client-centred discipline. However, as far
      as physical functioning is concerned, it is possible that the professional makes
      an "a priori" judgement, considering the objective clinical data regardless of
      the patient's subjective experience of his/her illness.

PMID- 23557401
TI  - A qualitative study of stakeholder views on the effects of provider payment on
      cooperation, quality of care and cost-containment in integrated stroke care.
AB  - BACKGROUND: Stroke services are a form of integrated care which have been
      introduced in many countries, including the Netherlands, to improve health
      outcomes and processes of care by connecting the acute, rehabilitative, and
      chronic phases of stroke care. Limited research exists on the effects of payment
      systems on the functioning of integrated care services from the perspectives of
      those involved in providing, planning and contracting the care. This qualitative
      study identified stakeholder views on i) challenges in integrated stroke care
      associated with fee-for-service systems; ii) other possible financing models for
      stroke care, and iii) challenges in the implementation of an integrated financing
      mechanism for stroke care. METHODS: Twenty-four participants were interviewed
      using face-to-face audio-recorded semi-structured interviews. Respondents were
      purposively selected from five stakeholder groups; care providers, health care
      managers, health insurers, experts and patient representatives. Transcribed data
      were coded and analysed to generate themes relating to the study aims. RESULTS:
      Respondents mentioned the following challenges associated with the current fee
      for-service system; inappropriate incentives for cooperation, efficiency and
      improving quality and the inability to exert steering power at the level of the
      stroke service. In addition, care is not patient-centred and the financing system
      is inflexible.The respondents mentioned several solutions for the challenges, but
      there was no consensus amongst them. Regarding the implementation of integrated
      financing, respondents mentioned the following general challenges; a) the
      foundations of the financing system are incompatible with integrated financing,
      b) co-morbidity and c) the lack of evidence on the effect of integrated
      financing. Stroke-specific challenges were; a) the diverse patient population, b)
      a non-uniform care trajectory, c) unclear division of responsibility for the
      overall care and d) different stages of development among stroke services.
      CONCLUSIONS: This study provides new knowledge on stakeholder perception of the
      effect of payment systems and financial incentives on cooperation processes,
      quality of care and cost-containment in integrated stroke care. The results show
      that fee-for-service does not provide the right incentives for the integration of
      stroke care. We recommend to perform financial experiments for integrated stroke
      care.

PMID- 23557402
TI  - NMR metabolomics analysis of the effects of 5-lipoxygenase inhibitors on
      metabolism in glioblastomas.
AB  - Changes across metabolic networks are emerging as an integral part of cancer
      development and progression. Increasing comprehension of the importance of
      metabolic processes as well as metabolites in cancer is stimulating exploration
      of novel, targeted treatment options. Arachidonic acid (AA) is a major component
      of phospholipids. Through the cascade catalyzed by cyclooxygenases and
      lipoxygenases, AA is also a precursor to cellular signaling molecules as well as
      molecules associated with a variety of diseases including cancer. 5-Lipoxygenase
      catalyzes the transformation of AA into leukotrienes (LT), important mediators of
      inflammation. High-throughput analysis of metabolic profiles was used to
      investigate the response of glioblastoma cell lines to treatment with 5
      lipoxygenase inhibitors. Metabolic profiling of cells following drug treatment
      provides valuable information about the response and metabolic alterations
      induced by the drug action and give an indication of both on-target and off
      target effects of drugs. Four different 5-lipoxygenase inhibitors and
      antioxidants were tested including zileuton, caffeic acid, and its analogues
      caffeic acid phenethyl ester and caffeic acid cyclohexethyl ester. A NMR approach
      identified metabolic signatures resulting from application of these compounds to
      glioblastoma cell lines, and metabolic data were used to develop a better
      understanding of the mode of action of these inhibitors.

PMID- 23557403
TI  - Docetaxel was effective in the management of metastatic angiosarcoma associated
      with disseminated intravascular coagulation syndrome.

PMID- 23557405
TI  - Heterocycle-heterocycle strategies: (2-nitrophenyl)isoxazole precursors to 4
      aminoquinolines, 1H-indoles, and quinolin-4(1H)-ones.
AB  - Reductive heterocycle-heterocycle (heterocycle -> heterocycle; H-H)
      transformations that give 4-aminoquinolines, 3-acylindoles, and quinolin-4(1H)
      ones from 2-nitrophenyl substituted isoxazoles are reported. When this
      methodology is applied to 3,5-, 4,5-, and 3,4-bis(2-nitrophenyl)isoxazoles,
      chemoselective heterocyclization gives quinolin-4(1H)-ones, and 4
      aminoquinolines, exclusively.

PMID- 23557406
TI  - Assessment of liver function: what are we measuring?

PMID- 23557404
TI  - Bioengineering organized, multilamellar human corneal stromal tissue by growth
      factor supplementation on highly aligned synthetic substrates.
AB  - Recapitulating the microstructure of the native human corneal stromal tissue is
      believed to be a key feature in successfully engineering the corneal tissue. The
      stratified multilayered collagen fibril lamellae with orthogonal orientation
      determine the robust biomechanical properties of this tissue, and the uniform
      collagen fibril size and interfibrillar spacing are critical to its optical
      transparency. The objective of this investigation was to develop a highly
      organized collagen-fibril construct secreted by human corneal stromal stem cells
      (hCSSCs) to mimic the human corneal stromal tissue. In culture on a highly
      aligned fibrous substrate made from poly(ester urethane) urea, the fibroblast
      growth factor-2 (FGF-2, 10 ng/mL) and transforming growth factor-beta 3 (TGF
      beta3, 0.1 ng/mL) impacted the organization and abundance of the secreted
      collagen fibril matrix. hCSSCs differentiated into keratocytes with significant
      upregulation of the typical gene markers, including KERA, B3GnT7, and CHST6. FGF
      2 treatment stimulated hCSSCs to secrete collagen fibrils strongly aligned in a
      single direction, whereas TGF-beta3 induced collagenous layers with orthogonal
      fibril orientation. The combination of FGF-2 and TGF-beta3 induced multilayered
      lamellae with orthogonally oriented collagen fibrils, in a pattern mimicking the
      human corneal stromal tissue. The constructs were 60-70 MUm thick and had an
      increased content of cornea-specific extracellular matrix components, including
      keratan sulfate, lumican, and keratocan. The approach of combining substrate cues
      with growth factor augmentation offers a new means to engineer well-organized,
      collagen-based constructs with an appropriate nanoscale structure for corneal
      repair and regeneration.

PMID- 23557407
TI  - To drain or not to drain: a cumulative meta-analysis of the use of routine
      abdominal drains after pancreatic resection.
AB  - BACKGROUND: To warrant the adoption or rejection of health care interventions in
      daily practice, it is important to establish the point at which the available
      evidence is considered sufficiently conclusive. This process must avoid bias
      resulting from multiple testing and take account of heterogeneity across studies.
      The present paper addresses the issue of whether the available evidence may be
      considered sufficiently conclusive to continue or discontinue the current
      practice of postoperative abdominal drainage after pancreatic resection. METHODS:
      A systematic review was conducted of randomized and non-randomized studies
      comparing outcomes after routine intra-abdominal drainage with those after no
      drainage after pancreatic resection. Studies were retrieved from the PubMed,
      Cochrane Central Trial Register and EMBASE databases and meta-analysed
      cumulatively, adjusting for multiple testing and heterogeneity using the iterated
      logarithm method. RESULTS: Three reports, describing, respectively, one
      randomized and two non-randomized studies with a comparative design, met the
      inclusion criteria predefined for primary studies reporting on drain management
      and complications after pancreatic resection. These studies included 89, 179 and
      226 patients, respectively. The absolute differences in rates of postoperative
      complications in these studies were -6.4%, -9.5% and -6.3%, respectively, in
      favour of the no-drain groups. The cumulative risk difference in major
      complications, adjusted for multiple testing and heterogeneity, was -7.8%, with a
      95% confidence interval of -20.2% to 4.7% (P = 0.214). CONCLUSIONS: The routine
      use of abdominal drains after pancreatic resection may result in a higher risk
      for major complications, but the evidence is inconclusive.

PMID- 23557408
TI  - Early post-operative prediction of morbidity and mortality after a major liver
      resection for colorectal metastases.
AB  - BACKGROUND: An early prediction of poor outcomes is essential in the management
      of patients after a liver resection. The aim of this study was to evaluate the
      role of selected biochemical parameters on post-operative day 1 (POD 1) in the
      prediction of morbidity and mortality after a liver resection for colorectal
      metastases. METHOD: This retrospective study was based on 236 major liver
      resections for colorectal metastases performed between 2006 and 2011. Results of
      biochemical tests of blood samples obtained on POD 1 were assessed as predictors
      of primary outcome measures (hepatic and overall morbidity, 90-day mortality)
      using multiple regression and receiver-operating characteristics (ROC). RESULTS:
      Hepatic morbidity, overall morbidity and 90-day mortality rates were 18.6%, 28.0%
      and 4.7%, respectively. On the basis of multiple regression analysis and
      comparisons of the prediction models, serum bilirubin was selected for the
      prediction of hepatic (>2.05 mg/dl, sensitivity 69.2%, specificity 71.2%) and
      overall (>2.05 mg/dl, sensitivity 61.1% and specificity 71.2%) morbidity, and
      aspartate aminotransferase (AST) was selected for the prediction of 90-day
      mortality (>798 U/l, sensitivity 62.5% and specificity 90.4%). DISCUSSION:
      Biochemical analyses of blood on POD1 enables stratification of patients into low
      and high-risk groups for negative outcomes, with serum bilirubin associated with
      overall and hepatic morbidity and AST associated with mortality.

PMID- 23557409
TI  - Hepatic incidentaloma: the rule of tens.
AB  - OBJECTIVES: Hepatic incidentalomas (HI) are asymptomatic lesions detected
      incidentally during investigations for other pathologies. This prospective series
      outlines the management and outcomes of 121 HI managed over 7 years. METHODS:
      Data were recorded prospectively on 121 patients referred between 2003 and 2010
      for assessment of HI out of 1081 patients referred for a hepatic resection.
      Patients were reviewed in multidisciplinary meetings and investigated with tumour
      markers and radiological investigations. HI were classified as hypo- or
      hypervascular depending on arterial phase CT scan findings. Univariate and
      multivariate analysis was performed to define predictive factors for malignancy.
      RESULTS: Forty HI were hypovascular, 35 were benign (18 cysts, 12 focal fatty
      sparing, 1 fetal lobulation and 4 solitary necrotic nodules) and 5
      cholangiocarcinomas (all resected)]. Eighty-one HI were hypervascular, 72 were
      benign [40 focal nodular hyperplasia (FNH), 8 adenoma and 24 hemangiomas) and 9
      cancers (5 HCC, 4 metastases: 7 resected). Male gender [relative risk (RR) 2.70,
      confidence interval (CI) 1.69-3.51], age >45 years (RR 3.15, CI 2.71-3.89),
      tumour diameter >4 cm (RR 3.35, CI 3.13-4.01) and late (8 min) enhancement on
      magnetic resonace imaging (MRI) (RR 4.15, CI 3.01-4.79) were predictive of
      malignancy. CONCLUSIONS: HI constitute 10% of practice volume. 10% of hyper and
      hypovascular incidental lesions are malignant. Most can be treated aggressively
      after diagnosis.

PMID- 23557410
TI  - Reducing surgical site infections in hepatopancreatobiliary surgery.
AB  - OBJECTIVES: Patients undergoing complex hepatopancreatobiliary (HPB) operations
      are at high risk for surgical site infection (SSI). Factors such as biliary
      obstruction, operative time and pancreatic or biliary fistulae contribute to the
      high SSI rate. The purpose of this study was to analyse whether a multifactorial
      approach would reduce the incidence and cost of SSI after HPB surgery. METHODS:
      From January 2007 to December 2009, 895 complex HPB operations were monitored for
      SSI through the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP). In 2008, surgeon-specific SSI rates were
      provided to HPB surgeons, and guidelines for the management of perioperative
      factors were established. Observed SSI rates were monitored before and after
      these interventions. Hospital cost data were analysed and cost savings were
      calculated. RESULTS: Observed SSI for hepatic, pancreatic and complex biliary
      operations decreased by 9.6% over a 2-year period (P < 0.03). The excess cost per
      SSI was US$11 462 and was driven by increased length of stay and hospital
      readmission for infection. Surgeons rated surgeon-specific feedback on SSI rate
      as the most important factor in improvement. CONCLUSIONS: High SSI rates
      following complex HPB operations can be improved by a multifactorial approach
      that features process improvements, individual surgeon feedback and reduced
      variation in patient management.

PMID- 23557412
TI  - Development, validation and reliability of a web-based questionnaire to measure
      health-related quality of life in dogs.
AB  - OBJECTIVES: To describe the development, preliminary validation and reliability
      testing of a shortened web-based form of GUVQuest, a structured questionnaire to
      measure health-related quality of life in dogs. METHODS: The original 109 items
      were reduced using expert judgement and factor analysis. Validity was established
      by factor analysis and in a subsequent field trial using a "known groups"
      approach and classical test theory. Test-retest reliability was assessed using
      intraclass correlation coefficients. RESULTS: The instrument comprises 46 items
      each of which is rated by dog owners using a 7-point Likert scale. Factor
      analysis revealed a sensible structure containing four health-related quality of
      life domains (vitality, pain, distress and anxiety) accounting for 64.1% of the
      variability in the data. The field test involving 125 dogs demonstrated very good
      discriminative properties and intraclass correlation coefficient values of
      greater than 0.6. CLINICAL SIGNIFICANCE: This is the first report of a valid and
      reliable companion animal health-related quality of life instrument, the
      contemporary approach to animal welfare measurement, which is presented in a web
      based format, with automated production of a health-related quality of life
      profile. It offers major advantages to dog owners, practitioners and researchers.

PMID- 23557411
TI  - Prospective randomized trial of the effect of octreotide on pancreatic juice
      output after pancreaticoduodenectomy in relation to histological diagnosis, duct
      size and leakage.
AB  - BACKGROUND: Octreotide is generally administered based on the surgeon's
      interpretation of perceived risk for pancreatic fistula at the time of
      pancreaticoduodenectomy (PD). METHODS: A single-institution, prospective
      randomized trial was conducted between April 2009 and December 2011 involving 62
      PD patients who were randomized to receive octreotide (100 MUg subcutaneously
      every 8 h; n = 32) or placebo (n = 30). Pancreatic juice output was measured
      after the operation using a catheter inserted into the pancreatic duct.
      Postoperative complications were recorded. RESULTS: No significant differences in
      median output were found between the octreotide (82.5 ml) and placebo (77.5 ml)
      groups (P = 0.538). Median total output was significantly lower in patients with
      adenocarcinoma compared with those with periampullary tumours (P = 0.004) and in
      patients with a duct diameter of >5 mm compared with those with a duct diameter
      of <5 mm (P = 0.001). There were no significant differences in overall morbidity
      between the octreotide and placebo groups (P = 0.819). Grade B pancreatic fistula
      (International Study Group for Pancreatic Fistula) was observed in two and three
      patients in the octreotide and placebo groups, respectively. CONCLUSIONS:
      Morbidity did not differ significantly between the groups. This study did not
      demonstrate an inhibitory effect of octreotide on exocrine pancreatic secretion.
      Based on these results, the routine use of octreotide after PD cannot be
      recommended.

PMID- 23557413
TI  - Impact of a cybertutor in dermatological teaching.
AB  - BACKGROUND: The potential value of multimedia programs as an accessory instrument
      for medical education has already been demonstrated in several areas. However,
      most of them lack adequate validation. The authors proposed this study in order
      to develop and evaluate a computer multimedia program, aiming at providing a more
      attractive and state of the art learning tool in dermatology. METHODS: The
      cybertutor was developed containing clinical cases, self-education classes, and
      short video presentations. In order to evaluate its impact, 50 undergraduate
      students attending the third year of Medical School at UFRGS were randomized into
      two groups: group 1 was submitted to a multimedia program on a specific
      dermatological subject - parasite infestations, and group 2 to standard classes
      on the same subject. Both classes were taught by an experienced teacher, on the
      same subject and at the same time. In the end, the level of knowledge acquisition
      for the two groups was evaluated by a multiple choice test. RESULTS: The average
      of correct answers was 11.16 (SD = 1.625) in group 1 and 11.96 (SD = 1.645) in
      group 2. There were no statistically significant differences between the two
      groups (P = 0.09). The majority (80%) of the students who attended the cybertutor
      group showed interest in taking part in similar activities. CONCLUSIONS:
      According to this study, multimedia programs may be used for undergraduate
      education in Dermatology as a complementary educational tool. Contact with an
      instructor is still considered to be important and should be offered
      simultaneously.

PMID- 23557414
TI  - Phospholipase A(2) inhibition as potential therapy for inflammatory skin
      diseases.

PMID- 23557416
TI  - Conference scene: regulatory cells in autoimmunity: analyzing and moderating
      function.
AB  - The 2nd annual conference organized by EuroSciCon was aimed at understanding the
      various roles played by regulatory cells in autoimmunity. Several eminent
      researchers from all over Europe presented their novel findings at this
      conference. The presentations covered a wide range of topics from rheumatoid
      arthritis to multiple sclerosis to membrane lipids and environmental factors
      affecting immune responses.

PMID- 23557417
TI  - Bortezomib for the treatment of previously untreated multiple myeloma.
AB  - Management of multiple myeloma (MM) has been drastically changed in the last 10
      years thanks to the introduction of novel agents, which, combined with the
      backbone of classical chemotherapy, have led to a significant improvement in
      disease control. Bortezomib is the first reversible proteasome inhibitor approved
      for the treatment of MM, with wide synergism in vitro and in vivo with a plethora
      of drugs active for MM. In patients eligible for autologous stem cell
      transplantation (ASCT), the achievement of complete response or very good partial
      response before ASCT is associated with prolonged progression-free and overall
      survival. Thus, the goal of induction regimens should include, at least for
      younger patients, a continued improvement of the quality and depth of the
      achieved response. This article is focused on reviewing the major efforts in
      frontline therapy for MM, including bortezomib-containing induction regimens in
      patients either eligible or ineligible for ASCT.

PMID- 23557418
TI  - Targeting EBV's Achilles' heel with antigen-specific T cells.
AB  - Evaluation of: Icheva V, Kayser S, Wolff D et al. 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. J. Clin. Oncol. 31(1), 39-48 (2013). Adoptive transfer of donor
      derived EBV-specific T cells is an effective strategy for the prevention and
      treatment of EBV-associated post-transplant lymphoproliferative disease (PTLD).
      However, the time-consuming process of EBV-specific T-cell generation using
      standard protocols has limited their broader use. Ex vivo IFN-gamma capture assay
      is an attractive alternative for the rapid isolation of EBV-specific T cells. In
      the present study, Icheva et al. employ this method to rapidly isolate clinical
      grade T cells that are specific for EBNA1. Adoptive transfer of EBNA1-specific T
      cells was safe and resulted in clinical benefit in 7 out of 10 patients with EBV
      viremia and/or PTLD. Thus, T-cell therapy targeting a single EBV antigen, EBNA1,
      which is critical for EBV episome maintenance, may be sufficient for EBV-PTLD
      therapy in hematopoietic stem cells transplantation recipients.

PMID- 23557419
TI  - Complement-dependent cytotoxicity of an antibody to melanin in radioimmunotherapy
      of metastatic melanoma.
AB  - AIM: Novel treatments for metastatic melanoma are urgently needed. MATERIALS &
      METHODS: We developed radioimmunotherapy of metastatic melanoma using 6D2
      monoclonal antibody (mAb) to melanin with encouraging therapeutic results,
      preclinically and in patients. RESULTS: We observed tumor suppression with the
      unlabeled 6D2 mAb and investigated its tumoricidal mechanisms. In melanoma tumor
      bearing mice, we detected more complement-C3 deposition in the tumors from 188
      rhenium-labeled 6D2 mAb-treated mice when compared with untreated controls. 6D2
      and isotype-control mAb TEPC caused suppression of tumor growth in A2058 melanoma
      tumor-bearing mice. Tumors of mice treated with the unlabeled 6D2 mAb were
      infiltrated with more lymphocytes compared with controls. In vitro antibody
      dependent cell-mediated cytotoxicity did not contribute to the tumor-suppressive
      effect of 6D2 mAb, while 6D2 mAb demonstrated a strong effect on initiating
      complement-dependent cytotoxicity. CONCLUSION: We concluded that 6D2 mAb mediated
      complement-dependent cytotoxicity, resulting in killing of the tumor cells and
      suppression of tumor growth. These observations will help to improve the
      treatment protocols of radioimmunotherapy, as well as immunotherapy.

PMID- 23557420
TI  - Adjuvant immunotherapies as a novel approach to bacterial infections.
AB  - The rapid emergence of multidrug-resistant pathogens, especially Gram-negative
      bacteria and mycobacteria, represents one of the major medical challenges of the
      21st century. The gradual loss of effective classical antibiotics for many
      bacterial pathogens, combined with an increasing population density and mobility,
      urgently calls for the development of novel treatments. Here, we discuss the
      potential of adjuvant immunotherapies to selectively stimulate protective immune
      responses as a treatment option for bacterial infections. In order to elicit
      appropriate immune responses and to avoid unwanted inflammatory tissue damage, it
      is essential to identify ligands and receptor pathways that specifically control
      protective responses at the site of infection. We summarize existing data and
      discuss suitable candidate targets for future immunotherapies of infectious
      diseases.

PMID- 23557421
TI  - Radioimmunotherapy for hematopoietic cell transplantation.
AB  - Radioimmunotherapy (RIT) represents an attractive strategy to deliver radiation
      selectively to tumor and other target organs while minimizing toxicity to normal
      tissues. RIT with beta-particle-emitting isotopes targeting CD33, CD45 and CD66
      can potentially allow intensification of conditioning before hematopoietic cell
      transplantation (HCT) in leukemia. Similarly, RIT directed against CD20 has shown
      promise in the setting of autologous and allogeneic HCT for B-cell lymphomas.
      alpha-particle immunotherapy with isotopes such as bismuth-213, actinium-225 and
      astatinine-211 offers the possibility of more selective and efficient killing of
      target cells while sparing the surrounding normal cells. Pretargeting strategies
      may further improve target:normal organ dose ratios. While RIT has demonstrated
      significant antitumor activity, ultimately, randomized studies will be required
      to determine if conditioning regimens that include this therapeutic modality can
      improve patient outcomes after HCT.

PMID- 23557422
TI  - Radioimmunotherapy for peritoneal cancers.
AB  - Peritoneal carcinomatosis is the most common secondary cancerous disease to
      affect the peritoneal cavity, implying poor prognosis. Standard therapy consists
      of cytoreductive surgery in combination with adjuvant chemotherapy. To improve
      the therapeutic outcome, targeted therapy using radionuclides such as alpha-,
      beta- and Auger emitters coupled to antibodies seems a promising option. Although
      beta-emitters have shown promising results in preclinical and clinical Phase I/II
      studies, these results could not be confirmed in Phase III studies. Because alpha
      particles very efficiently eradicate small tumor cell nodules, they represent a
      promising option for treatment of micrometastatic disease characteristic of
      peritoneal carcinomatosis. alpha-emitter radioimmunoconjugates have been
      successfully used in various experimental studies and in a first clinical Phase I
      study in human ovarian cancer. Although confirmation of these results in clinical
      trials is missing and problems still exist concerning worldwide availability,
      alpha-emitters could contribute to optimizing strategies for therapy of
      peritoneal carcinomatosis.

PMID- 23557424
TI  - Lymphoproliferative disorders in immunocompromised individuals and therapeutic
      antibodies for treatment.
AB  - The incidence of lymphoproliferative disease (LPD) is significantly higher in
      individuals who have congenital, acquired or iatrogenically induced
      immunodeficiency. Although there are a wide range of LPDs including lymphoma and
      leukemia, this article only covers LPDs in patients with impaired immune
      function, which are called immunodeficiency-associated LPDs (ID-LPDs). Three of
      the four ID-LPD categories recognized by WHO have been selected for discussion:
      LPD in primary immune disorders, post-transplant LPD and LPD in HIV infection.
      Because of the high incidence and mortality of ID-LPDs, careful evaluation of the
      morphology, immunophenotype, genotype, viral status and clinical history is
      required for accurate diagnosis and treatment. Recently, treatment with
      monoclonal antibodies (mAbs) has been widely used and developed because of its
      potential benefits. The aim of this review is to describe new information
      concerning mAb treatment in LPDs and to draw physicians' attention to mAb
      therapy, which should be effective for some types of LPD.

PMID- 23557423
TI  - T-cell therapies for HIV.
AB  - Antiretroviral therapy has improved the quality of life for HIV(+) individuals
      but efficacy requires strict adherence and treatment is not curative. Recently,
      the use of T cells as therapeutic agents has been in the spotlight in the
      settings of post-transplant opportunistic infections and cancer. Whether T-cell
      therapy can be harnessed for treating HIV remains to be determined but there are
      a few studies that seek to answer that question. Infusion of ex vivo-expanded HIV
      specific T cells showed limited efficacy but no adverse events. Genetically
      modified T cells expressing CD4 chimeric antigen receptors have recently been
      shown to have persistence that outperforms chimeric antigen receptors used for
      cancers. Although the results have not yet been published for many clinical
      studies using T cells for HIV, preclinical studies and the clinical data that are
      available highlight the potential for T-cell therapy to decrease or eliminate HIV
      patients' dependency on antiretroviral therapy.

PMID- 23557425
TI  - Role of bexarotene in the treatment of cutaneous T-cell lymphoma: the clinical
      and immunological sides.
AB  - Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoid
      neoplasms. The incidence of CTCLs has risen over the last three decades. The most
      common CTCLs are mycosis fungoides and Sezary syndrome. Therapies for CTCLs are
      various and range from skin-directed therapy to chemotherapy. Retinoids have been
      used in CTCL treatment since the 1980s with good results. Bexarotene is the first
      retinoid approved by the US FDA for CTCL therapy. Since then, numerous
      experiences of both its efficacy and mechanism of action have been reported. The
      aim of this paper is to review bexarotene action on CTCLs, as well as to
      highlight its immunological targets.

PMID- 23557427
TI  - Correction: Mechanisms of stomatal development: an evolutionary view.

PMID- 23557428
TI  - Fruit and vegetable exposure in children is linked to the selection of a wider
      variety of healthy foods at school.
AB  - Schools often offer healthy fruits and vegetables (FV) and healthy entrees.
      However, children may resist these efforts due to a lack of familiarity with the
      offerings. While numerous exposures with a food increase its liking, it may be
      that an exposure to a variety of FV at home leads to greater willingness to
      select other foods - even those that are unrelated to those eaten at home. As an
      initial test of this possibility, this study was designed to examine how self
      reports of exposure and consumption of various FV were associated with the
      selection of FV and lunch entrees at school. Participants (n = 59) were a
      convenience sample of elementary children. A median split was used to place
      students into high- and low-exposure groups for self-reports of both exposure and
      consumption at home. The primary dependent variables were self-reports of
      selecting FV at school; the children's absolute and relative ratings of eight
      'healthier' lunch entrees; and self-reports of selecting these entrees. These
      entrees were recently added to the school menu and, therefore, tended to be less
      familiar to children. Food ratings were collected through taste exposures
      conducted at school. Results indicate that children who reported more frequent
      exposure to FV at home consumed a wider variety of FV at school and were more
      likely to report selecting 'healthier' entrees at school lunch. These data
      suggest that exposure to, and the consumption of, a variety of FV may make
      children more willing to select a wider range of FV and other healthy entrees. 

PMID- 23557430
TI  - Biomechanical diagnosis of keratoconus: evaluation of the keratoconus match index
      and the keratoconus match probability.
AB  - PURPOSE: To evaluate the diagnostic capacity of the Ocular Response Analyser's
      keratoconus match index (KMI) and keratoconus match probability (KMP)
      classification in a sample of keratoconus (KC) patients. METHODS: Keratoconus
      match index and KMP from 114 KC eyes, randomly selected from 114 patients with
      bilateral keratoconus (KCG), were compared with the corresponding ones from 109
      normal eyes (CG). Keratoconus match index's predictive accuracy was assessed by
      receiver operating curves (ROC). Keratoconus match probability level of agreement
      was evaluated at the different KC stages of the Amsler-Krumeich classification.
      Correlations were estimated with topographic keratoconus classification (TKC),
      keratoconus index (KI), index of surface variance (ISV), vertical asymmetry
      (IVA), height asymmetry (IHA), height decentration (IHD), minimal radius (Rmin),
      central corneal thickness (CCT), thinnest corneal thickness (TCT) mean
      keratometry (Km) and intraocular pressure (IOPg). RESULTS: Mean KMI in KCG and CG
      was 0.20 +/- 0.38 and 0.98 +/- 0.25, respectively (p < 0.01). Significant KMI
      differences (p < 0.01) were detected in different KC groups [range: 0.62 +/- 0.38
      (KC 1), -0.62 +/- 0.04 (KC 4)]. Significant correlation was detected between KC
      staging and KMI (r = -0.56, p < 0.0001). Keratoconus match probability identified
      22.03% of the CG eyes as suspect. Moreover, KMP identified 7.01% and 23.68% of
      the KCG eyes as normal and suspect, respectively. Receiver operating curves
      analysis for KMI parameter indicated a predictive accuracy of 97.7% (cut-off
      point: 0.512, sensitivity: 91.18%, specificity: 94.34%). CONCLUSIONS: Keratoconus
      match index seems to be a reliable index in keratoconus diagnosis and staging.
      Keratoconus match probability identifies a significant percentage of
      topographically defined KC and CG eyes as suspect. Diagnostic capacity of these
      novel indexes needs to be further explored.

PMID- 23557431
TI  - 3D transthoracic echocardiography of Brucella endoaortitis and endocarditis of
      the aortic valve and ascending aorta.

PMID- 23557429
TI  - Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder
      depression.
AB  - BACKGROUND: The literature on the neuropsychological profiles in Bipolar disorder
      (BD) depression is sparse. The aims of the study were to assess the
      neurocognitive profiles in treatment-resistant, acutely admitted BD depression
      inpatients, to compare the neurocognitive functioning in patients with BD I and
      II, and to identify the demographic and clinical illness characteristics
      associated with cognitive functioning. METHODS: Acutely admitted BD I (n = 19)
      and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major
      depressive episode were tested with the MATRICS Consensus Cognitive Battery
      (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult
      Reading Test, and a battery of clinical measures. RESULTS: Neurocognitive
      impairments were evident in the BD I and BD II depression inpatients within all
      MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I
      group than in the BD II group, with a significant difference on one of the
      measures, category fluency. 68.4% of the BD I patients had clinically significant
      impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5%
      of the BD II patients (p = 0.045). A significant reduction in IQ from the
      premorbid to the current level was seen in BD I but not BD II patients. Higher
      age was associated with greater neurocognitive deficits compared to age-adjusted
      published norms. CONCLUSIONS: A high proportion of patients with therapy
      resistant BD I or II depression exhibited global neurocognitive impairments with
      clinically significant severity. The cognitive impairments were more common in BD
      I compared to BD II patients, particularly processing speed. These findings
      suggest that clinicians should be aware of the severe neurocognitive dysfunction
      in treatment-resistant bipolar depression, particularly in BD I. TRIAL
      REGISTRATION: NCT00664976.

PMID- 23557432
TI  - Effect of pregnancy on gingival inflammation in systemically healthy women: a
      systematic review.
AB  - AIM: To obtain an overall quantitative estimate of the association between
      pregnancy and gingival inflammation. MATERIAL AND METHODS: Medline and EMBASE
      databases were searched through August 2011. Prospective cohort or cross
      sectional studies assessing the effect of pregnancy on gingival inflammation
      evaluated by the gingival index (GI) and/or bleeding on probing were included.
      Meta-analyses were performed if possible. RESULTS: Forty-four articles
      representing 33 studies (14 cohort and 19 cross-sectional) were included. Meta
      analyses, performed whenever possible, revealed (1) a significantly lower GI in
      pregnant women in the first term compared with those in their second or third
      term of pregnancy; (2) a lower mean GI score in post-partum women compared with
      women in their second [WMD = 0.143; 95% CI (0.031; 0.255); p = 0.012] or third
      term [WMD = 0.256; 95% CI (0.151; 0.360); p < 0.001] of pregnancy, when
      considering cohort studies; (3) Non-pregnant women had lower mean GI values than
      women in their second or third term of pregnancy. Small changes in plaque levels
      were reported. CONCLUSION: Despite the limited number of studies included in the
      meta-analyses, the present systematic review confirms the existence of a
      significant increase in GI throughout pregnancy and between pregnant versus post
      partum or non-pregnant women, without a concomitant increase in plaque levels.

PMID- 23557433
TI  - Adjunctive photodynamic therapy to non-surgical treatment of chronic
      periodontitis: a systematic review and meta-analysis.
AB  - AIM: To investigate the efficacy of antimicrobial photodynamic therapy (aPDT)
      adjunctive to scaling root planing (SRP) in patients with chronic periodontitis.
      METHODS: A meta-analysis was conducted according to the PRISMA statement and
      Cochrane Collaboration recommendations. Two independent reviewers performed an
      extensive literature search and manual search on seven databases. Mean
      differences (MD) and 95% confidence intervals (CI) were calculated for clinical
      attachment level (CAL) gain and probing depth (PD) reduction. The I(2) test was
      used for inter-study heterogeneity. Publication bias was examined by Egger's
      regression test and the trim-and-fill method. RESULTS: Sensitivity analysis of 14
      randomized clinical trials (RCTs) revealed differences in PD reduction (MD 0.19,
      95% CI 0.07-0.31, p = 0.002) and CAL gain (MD 0.37, 95% CI 0.26-0.47, p < 0.0001)
      in favour of SRP + aPDT, with no evidence of heterogeneity. Subgroup analysis
      revealed the absence of heterogeneity in RCTs, with high risk of bias for PD
      reduction and CAL gain. No evidence of publication bias was detected.
      CONCLUSIONS: The use of adjunctive aPDT to conventional SRP provides short-term
      benefits. The evidence to support its clinical medium/long-term efficacy is
      insufficient. Further high-quality RCTs are needed to investigate the influence
      of potential confounders on the efficacy of adjunctive aPDT.

PMID- 23557434
TI  - Critical appraisal of systematic reviews on the effect of a history of
      periodontitis on dental implant loss.
AB  - OBJECTIVE: To perform a systematic critical appraisal of the methodological
      quality of systematic reviews on the effect of a history of periodontitis on
      dental implant loss. MATERIALS & METHODS: PubMed, the Cochrane database for
      systematic reviews, the DARE, Biosis Preview, CINAHL, Web of Science, and LILACS
      electronic databases were searched on 16th June 2012, independently and in
      duplicate, for systematic reviews and meta-analyses related to dental implants
      for patients with and without a history of periodontitis. Manual searching of the
      reference lists of included papers was also conducted. The methodological quality
      of these systematic reviews was assessed by use of the AMSTAR and R-AMSTAR
      checklists. Before quality assessment was initiated, the reviewers were
      calibrated until they achieved excellent agreement. RESULTS: Sixty-eight papers
      were initially retrieved. Of these, nine systematic reviews and three meta
      analyses were included. Some domains, for example, "characteristics of the
      included studies" were satisfied in both checklists. In contrast, domains such as
      "comprehensive literature search" and "assessment of likelihood of publication
      bias" were rarely met. CONCLUSION: Much methodological variability was
      encountered in the selected reviews. To furnish readers with a more comprehensive
      assessment of the evidence, authors should observe higher standards when
      conducting and reporting their reviews.

PMID- 23557435
TI  - Silver nanoassemblies constructed from boranephosphonate DNA.
AB  - Spatially selective deposition of metal onto complex DNA assemblies is a
      promising approach for the preparation of metallic nanostructures with features
      that are smaller than what can be produced by top-down lithographic techniques.
      We have recently reported the ability of 2'-deoxyoligonucleotides containing
      boranephosphonate linkages (bpDNA) to reduce AuCl4(-), Ag(+), and PtCl4(2-) ions
      to the corresponding nanoparticles. Here we demonstrate incorporation of bpDNA
      oligomers into a two-dimensional DNA array comprised of tiles containing double
      crossover junctions. We further demonstrate the site-specific deposition of
      metallic silver onto this DNA structure which generates well-defined and
      preprogrammed arrays of silver nanoparticles. With this approach the size of the
      metallic features that can be produced is limited only by the underlying DNA
      template. These advances were enabled due to a new method for synthesizing bpDNA
      that uses a silyl protecting group on the DNA nucleobases during the solid-phase
      2'-deoxyoligonucleotide synthesis.

PMID- 23557438
TI  - Haemophilia care in Europe - a survey of 35 countries.
AB  - A questionnaire was circulated in 2012 to national haemophilia patient
      organizations in Europe affiliated to the European Haemophilia Consortium (EHC)
      and the World Federation of Hemophilia (WFH) to seek information about the
      organization of haemophilia care and treatment available at a national level. The
      35 responses received highlighted major differences in the availability of
      treatment and care. There was a wide range in factor VIII consumption with usage
      ranging from 0.20 IU per capita in Armenia to 8.56 IU per capita in Sweden
      (median: IU per capita). The decrease in health budgets in many countries was not
      matched by decreases in use of FVIII per capita. In the 19 countries that
      responded to the previous survey, there was a significant improvement in access
      to prophylaxis and home treatment.

PMID- 23557437
TI  - Exposure of silver-nanoparticles and silver-ions to lung cells in vitro at the
      air-liquid interface.
AB  - BACKGROUND: Due to its antibacterial properties, silver (Ag) has been used in
      more consumer products than any other nanomaterial so far. Despite the promising
      advantages posed by using Ag-nanoparticles (NPs), their interaction with
      mammalian systems is currently not fully understood. An exposure route via
      inhalation is of primary concern for humans in an occupational setting. Aim of
      this study was therefore to investigate the potential adverse effects of
      aerosolised Ag-NPs using a human epithelial airway barrier model composed of
      A549, monocyte derived macrophage and dendritic cells cultured in vitro at the
      air-liquid interface. Cell cultures were exposed to 20 nm citrate-coated Ag-NPs
      with a deposition of 30 and 278 ng/cm2 respectively and incubated for 4 h and 24
      h. To elucidate whether any effects of Ag-NPs are due to ionic effects, Ag
      Nitrate (AgNO3) solutions were aerosolised at the same molecular mass
      concentrations. RESULTS: Agglomerates of Ag-NPs were detected at 24 h post
      exposure in vesicular structures inside cells but the cellular integrity was not
      impaired upon Ag-NP exposures. Minimal cytotoxicity, by measuring the release of
      lactate dehydrogenase, could only be detected following a higher concentrated
      AgNO3-solution. A release of pro-inflammatory markers TNF-alpha and IL-8 was
      neither observed upon Ag-NP and AgNO3 exposures as well as was not affected when
      cells were pre-stimulated with lipopolysaccharide (LPS). Also, an induction of
      mRNA expression of TNF-alpha and IL-8, could only be observed for the highest
      AgNO3 concentration alone or even significantly increased when pre-stimulated
      with LPS after 4 h. However, this effect disappeared after 24 h. Furthermore,
      oxidative stress markers (HMOX-1, SOD-1) were expressed after 4 h in a
      concentration dependent manner following AgNO3 exposures only. CONCLUSIONS: With
      an experimental setup reflecting physiological exposure conditions in the human
      lung more realistic, the present study indicates that Ag-NPs do not cause adverse
      effects and cells were only sensitive to high Ag-ion concentrations. Chronic
      exposure scenarios however, are needed to reveal further insight into the fate of
      Ag-NPs after deposition and cell interactions.

PMID- 23557439
TI  - Cluster-based exposure variation analysis.
AB  - BACKGROUND: Static posture, repetitive movements and lack of physical variation
      are known risk factors for work-related musculoskeletal disorders, and thus needs
      to be properly assessed in occupational studies. The aims of this study were (i)
      to investigate the effectiveness of a conventional exposure variation analysis
      (EVA) in discriminating exposure time lines and (ii) to compare it with a new
      cluster-based method for analysis of exposure variation. METHODS: For this
      purpose, we simulated a repeated cyclic exposure varying within each cycle
      between "low" and "high" exposure levels in a "near" or "far" range, and with
      "low" or "high" velocities (exposure change rates). The duration of each cycle
      was also manipulated by selecting a "small" or "large" standard deviation of the
      cycle time. Theses parameters reflected three dimensions of exposure variation,
      i.e. range, frequency and temporal similarity.Each simulation trace included two
      realizations of 100 concatenated cycles with either low (rho = 0.1), medium (rho
      = 0.5) or high (rho = 0.9) correlation between the realizations. These traces
      were analyzed by conventional EVA, and a novel cluster-based EVA (C-EVA).
      Principal component analysis (PCA) was applied on the marginal distributions of
      1) the EVA of each of the realizations (univariate approach), 2) a combination of
      the EVA of both realizations (multivariate approach) and 3) C-EVA. The least
      number of principal components describing more than 90% of variability in each
      case was selected and the projection of marginal distributions along the selected
      principal component was calculated. A linear classifier was then applied to these
      projections to discriminate between the simulated exposure patterns, and the
      accuracy of classified realizations was determined. RESULTS: C-EVA classified
      exposures more correctly than univariate and multivariate EVA approaches;
      classification accuracy was 49%, 47% and 52% for EVA (univariate and
      multivariate), and C-EVA, respectively (p < 0.001). All three methods performed
      poorly in discriminating exposure patterns differing with respect to the
      variability in cycle time duration. CONCLUSION: While C-EVA had a higher accuracy
      than conventional EVA, both failed to detect differences in temporal similarity.
      The data-driven optimality of data reduction and the capability of handling
      multiple exposure time lines in a single analysis are the advantages of the C
      EVA.

PMID- 23557440
TI  - Is human cytomegalovirus associated with breast cancer progression?
AB  - BACKGROUND: It has been hypothesized that human cytomegalovirus (HCMV) may be
      associated with breast cancer progression. However, the role of HCMV infection in
      breast cancer remains controversial. We aimed to assess whether HCMV genes (UL122
      and UL83) could be detected in breast carcinomas and reinvestigated their
      possible association with breast cancer progression. DNA from paraffin-embedded
      tissues was analyzed by real-time PCR. We investigated 20 fibroadenomas and 27
      primary breast carcinomas (stages II, III, and IV). FINDINGS: Two carcinomas were
      positive for HCMV, one was positive for two TaqMan viral detection probes, and
      one was positive for a sole TaqMan viral detection probe (UL83), whereas the
      remainder of the samples was negative. CONCLUSIONS: Samples studied showed no
      association between HCMV infection and breast cancer progression.

PMID- 23557441
TI  - Theoretical study of topographical features around the conical intersections of
      fluorene-based light-driven molecular rotary motor.
AB  - Topographical features around the conical intersection (CIX) of a fluorene-based
      light-driven molecular rotary motor have been examined by means of ab initio
      molecular orbital calculations. The model molecule is a derivative of 9-(2-phenyl
      2-cyclopenten-1-ylidene)-9H-fluorene (PCPF) where PCPF is bridged by a
      pentamethylene chain between the 2 position of the phenyl group and the
      pseudoaxial position of the C(5) atom in the 2-cyclopenten-1-ylidene ring. This
      model molecule (denoted by M5-PCPF) has been very recently reported as a
      candidate for a light-driven molecular motor with constant rotation. The conical
      intersection for the photoprocess of the ethylenic C?C torsion reported there
      (denoted by CIX1), which exclusively leads to a product of P'-M5-PCPF, is found
      to be classified as a sloped-type CIX. Another CIX reported at the present time
      (CIX2) exclusively goes back to a reactant of P-M5-PCPF, whereas CIX2 is also
      classified as a sloped-type CIX. At the stable geometry in S1 around the CIX
      region (S1-geometry), the 2-cyclopenten-1-ylidene rotor takes a perpendicular
      twist against the fluorene stator, but the fluorene stator does not wag so much
      against the C?C rotary axis. The wagging motions of the fluorene stator from S1
      geometry to the opposite directions lead to CIX1 and CIX2, respectively.

PMID- 23557436
TI  - Requirements for innate immune pathways in environmentally induced autoimmunity.
AB  - There is substantial evidence that environmental triggers in combination with
      genetic and stochastic factors play an important role in spontaneous autoimmune
      disease. Although the specific environmental agents and how they promote
      autoimmunity remain largely unknown, in part because of diverse etiologies,
      environmentally induced autoimmune models can provide insights into potential
      mechanisms. Studies of idiopathic and environmentally induced systemic
      autoimmunity show that they are mediated by common adaptive immune response
      genes. By contrast, although the innate immune system is indispensable for
      autoimmunity, there are clear differences in the molecular and cellular innate
      components that mediate specific systemic autoimmune diseases, suggesting
      distinct autoimmune-promoting pathways. Some of these differences may be related
      to the bifurcation of toll-like receptor signaling that distinguishes interferon
      regulatory factor 7-mediated type I interferon production from nuclear factor
      kappaB-driven proinflammatory cytokine expression. Accordingly, idiopathic and
      pristane-induced systemic autoimmunity require both type I interferon and
      proinflammatory cytokines whereas the less aggressive mercury-induced
      autoimmunity, although dependent on nucleic acid-binding toll-like receptors,
      does not require type I interferon but needs proinflammatory cytokines. Scavenger
      receptors and the inflammasome may contribute to silica-induced autoimmunity.
      Greater understanding of the innate mechanisms responsible for idiopathic and
      environmentally induced autoimmunity should yield new information into the
      processes that instigate and drive systemic autoimmunity.

PMID- 23557444
TI  - In vitro evaluation of the effect of different endodontic sealers on retentive
      strength of fiber posts.
AB  - PURPOSE: There is limited information in the literature regarding the effect of
      different endodontic sealers on the bond strength of fiber posts luted with core
      buildup materials. The purpose of this study was to evaluate the effect of three
      different root canal sealers on the retentive strength of prefabricated fiber
      posts luted with a composite resin cement. MATERIALS AND METHODS: Fifty-four
      extracted single-rooted mandibular premolar teeth were prepared and randomly
      divided into three groups. The first two groups were obturated with gutta-percha
      and one of two eugenol-based root canal sealers (Endofil, Tubli-Seal). The third
      group (control) was obturated with gutta-percha and a resin-based root canal
      sealer (AH26). Prefabricated fiber posts were luted into the prepared post spaces
      with a composite resin cement (Multicore Flow). The pullout forces required for
      dislodgment of posts from their prepared post spaces were recorded. Data were
      collected and statistically analyzed. RESULTS: The AH26 group had significantly
      greater retentive strengths for the posts when compared with the Endofil and
      Tubli-Seal (eugenol-based sealers) groups (p<0.0001). There was no significant
      difference between the means of the retentive strengths for the Endofil and Tubli
      Seal groups (p=0.745). CONCLUSION: The chemical formulation of root canal sealers
      significantly affected the retentive strength for prefabricated fiber posts luted
      with a resin cement. Eugenol-based sealers significantly reduced the bond
      strength of prefabricated fiber posts luted with resin cement.

PMID- 23557442
TI  - Ebola virus VP35 induces high-level production of recombinant TPL-2-ABIN-2-NF
      kappaB1 p105 complex in co-transfected HEK-293 cells.
AB  - Activation of PKR (double-stranded-RNA-dependent protein kinase) by DNA plasmids
      decreases translation, and limits the amount of recombinant protein produced by
      transiently transfected HEK (human embryonic kidney)-293 cells. Co-expression
      with Ebola virus VP35 (virus protein 35), which blocked plasmid activation of
      PKR, substantially increased production of recombinant TPL-2 (tumour progression
      locus 2)-ABIN-2 [A20-binding inhibitor of NF-kappaB (nuclear factor kappaB) 2]-NF
      kappaB1 p105 complex. VP35 also increased expression of other co-transfected
      proteins, suggesting that VP35 could be employed generally to boost recombinant
      protein production by HEK-293 cells.

PMID- 23557445
TI  - Repigmentation of leukotrichia in vitiligo with transplantation of cultured
      autologous melanocytes.

PMID- 23557448
TI  - Terminal psychiatric illness.

PMID- 23557447
TI  - Risk factors for a prolonged operative time in a single-incision laparoscopic
      cholecystectomy.
AB  - BACKGROUND: A prolonged operative time is associated with adverse post-operative
      outcomes in laparoscopic surgery. Although a single-incision laparoscopic
      cholecystectomy (SILC) requires a longer operative time as compared with a
      conventional laparoscopic cholecystectomy, risk factors for a prolonged operative
      time in SILC remain unknown. METHODS: A total of 20 clinical variables were
      retrospectively reviewed to identify factors for a prolonged operative time
      (longer than 3 h) in a total of 220 consecutive patients undergoing SILC.
      RESULTS: The median operative time was 145 min (range, 55-435) and a prolonged
      operative time was required in 62 patients (28%). Independent factors that
      predict a prolonged operative time as identified through multivariate analysis
      were body mass index (BMI) (P = 0.009), acute cholecystitis (P < 0.001) and
      operator (resident or staff surgeon) (P < 0.001). Furthermore, a prolonged
      operative time was significantly associated with an increased amount of intra
      operative blood loss (P < 0.001) and a prolonged stay after surgery (P < 0.001).
      CONCLUSIONS: These findings suggest that a higher BMI, acute cholecystitis and a
      resident as an operator significantly increase the duration of SILC procedures.

PMID- 23557449
TI  - Biological perspectives: hydroxyzine for anxiety: another look at an old drug.

PMID- 23557450
TI  - Psychogenic nonepileptic seizures: a pilot study of a brief educational
      intervention.
AB  - PURPOSE: Attending to psychological support and education from the time of
      diagnosis will assist patients in their acceptance of the need for psychological
      services. DESIGN AND METHODS: An intervention was provided at the time of
      diagnosis of psychogenic nonepileptic seizures. This randomized control pilot
      study examined outcomes 6-8 weeks after discharge from the hospital. FINDINGS:
      All subjects in the treatment group made and/or kept an appointment with a
      psychotherapist or psychiatrist within 6-8 weeks of discharge from the hospital
      as compared with 50% of the control group. PRACTICE IMPLICATIONS: This supportive
      approach assists patients to accept the functional or nonorganic nature of their
      symptoms and the need for psychological services.

PMID- 23557451
TI  - Who cares if it is a hate crime? Lesbian, gay, bisexual, and transgender hate
      crimes--mental health implications and interventions.
AB  - PURPOSE: The purpose of this paper was to discuss lesbian, gay, bisexual, or
      transgender-targeted hate crimes and their mental health consequences for the
      victim and community. CONCLUSIONS: Hate crimes are typically more violent than
      nonhate-motivated crimes and have more deleterious mental health consequences.
      PRACTICE IMPLICATIONS: Thorough assessment coupled with an understanding of the
      social milieu and the meaning of the experience to the survivor can help the
      psychiatric nurse partner with the client to select the most appropriate
      treatment.

PMID- 23557452
TI  - Nurses' attitudes toward clients with substance use problems.
AB  - PURPOSE: This study aimed to examine factors associated with nurses' attitudes
      toward clients with substance use problems. DESIGN AND METHODS: A cross-sectional
      design was used, and 489 nurses working in two medical centers in Taiwan
      participated in this study. FINDINGS: Age, total nursing experience, work unit,
      personal experience, experience of taking care of clients with substance use
      problems, substance use education in school, and continuing education were
      significantly associated with nurses' attitudes. Hierarchical regression revealed
      that continuing education predicted nurses' overall attitudes. However, the model
      explained a low variance. PRACTICE IMPLICATIONS: Education-focused training alone
      may not be adequate. Nursing workforce development needs to incorporate multiple
      strategies, including clinical supervision, when designing substance use
      education for clinical nurses in order to generate better improvements on
      attitudes.

PMID- 23557453
TI  - Closing an open psychiatric ward: organizational change and its effect on staff
      uncertainty, self-efficacy, and professional functioning.
AB  - PURPOSE: Converting an open psychiatric ward to a closed one can be threatening
      and stressful for the medical and nursing staff involved. This study describes
      the effects of this change, in particular the before-after correlation among self
      efficacy, professional functioning, and uncertainty. DESIGN AND METHODS: Forty
      four staff participated, completing pre-/poststructured questionnaires. FINDINGS:
      Uncertainty was higher before the conversion than after the conversion.
      Professional functioning declined after the conversion. Self-efficacy was
      positively correlated with pre- and postconversion functioning, but negatively
      correlated with postconversion uncertainty. PRACTICE IMPLICATIONS: It is
      important to prepare staff for this significant organizational change.
      Suggestions for prechange interventions are offered.

PMID- 23557454
TI  - The effects on helplessness and recovery of an empowerment program for
      hospitalized persons with schizophrenia.
AB  - PURPOSE: The study aim was to evaluate the effects on helplessness and recovery
      of an empowering program for patients with chronic schizophrenia. DESIGN AND
      METHODS: A repeated-measure design with a control group was used. The subjects
      consisted of 46 patients with schizophrenia admitted in three psychiatric
      hospitals in South Korea. The experimental group (n = 23) received the empowering
      program twice a week for 60 min, with a total of 6 weeks. FINDINGS: This finding
      revealed that the empowering program was effective on helplessness (F = 185.218,
      p <.001) and recovery (F = 159.402, p <.001, F = 34.154, p <.001) of hospitalized
      persons with schizophrenia. PRACTICE IMPLICATIONS: This study demonstrated that
      the empowering program can be a useful psychiatric nursing intervention.

PMID- 23557455
TI  - Clinical supervision for transition to advanced practice.
AB  - PURPOSE: This reflective paper offers a conceptual framework of clinical
      supervision that assists supervisors to create supportive relationships necessary
      for advanced practice development. CONCLUSIONS: Combining established concepts of
      clinical supervision with systems psychodynamics enhances the supervisory
      experience. It is useful to supervisors to understand role transition as it
      sensitizes them to what their supervisees experience. PRACTICE IMPLICATIONS:
      Nurses require support in role transition, especially when the systems into which
      they are introduced can struggle with new advanced roles. This framework offers a
      broadened lens that allows for the richness and complexities that go with the
      development of advanced practice to be explored and better understood.

PMID- 23557456
TI  - The art of mental health practice: the role of drama in developing empathy.
AB  - PURPOSE: This paper explores concepts central to acting, and details how these
      concepts can be related to mental health nursing practice. DESIGN AND METHODS:
      The work of the acting theorists Constantin Stanislavski and Lee Strasberg is
      examined and recontextualized to illustrate how their work is relevant in modern
      mental health practice, and the development of empathy. FINDINGS: While these
      concepts are still utilized in drama, they have not been fully explored in their
      original context. Their use could combat stress and burnout, heighten awareness,
      and enhance the projection of emotions. PRACTICE IMPLICATIONS: These concepts can
      be linked with reflective practice in mental health, and a stronger emphasis on
      the values of this approach could allow the nurse to strengthen the level of
      empathy they demonstrate.

PMID- 23557457
TI  - Sleep disturbance in family caregivers of individuals with dementia: a review of
      the literature.
AB  - PURPOSE: This paper will review published evidence regarding health outcomes and
      factors associated with caregivers' sleep disturbance. DESIGN AND METHODS:
      Searches were conducted on CINAHL, MEDLINE, PubMed, and PsycINFO using various
      keywords. FINDINGS: We evaluated 138 abstracts and reviewed 18 articles.
      Depression is the most reported factor influencing caregivers' sleep. Additional
      factors are caregivers' psychological distress, demographic, and care recipients'
      characteristics. Health outcomes of sleep disturbance include poor mental and
      physical health, reduced quality of life, and elevated coagulation and
      inflammation levels. PRACTICE IMPLICATIONS: Clinicians should screen caregivers'
      sleep quality so they can assist them with suggestions on maintaining their
      health while performing caregiving tasks.

PMID- 23557458
TI  - Exhaled breath condensate formate after inhaled allergen provocation in atopic
      asthmatics in vivo.
AB  - OBJECTIVE: The dual actions of S-nitrosoglutathione reductase comprise reduction
      of S-nitrosoglutathione, a potent endogenous airway smooth muscle relaxant that
      is depleted in asthmatics, and detoxification of formaldehyde to formate. Airway
      formate production is increased in children with asthma, suggesting increased
      activity of S-nitrosoglutathione reductase. We determined formate in exhaled
      breath condensate from adult atopic asthmatics with asthma exacerbation produced
      by inhaled allergen in vivo, METHODS: Twenty-two adult atopic asthmatics
      underwent inhaled allergen challenge using specific allergen. Exhaled breath
      condensate was collected at baseline, 1 h after inhalation of the provocative
      dose of allergen, and then every 2 h for 8 h during the challenge. Formate was
      analyzed by ion chromatography, RESULTS: Eleven asthmatics developed an isolated
      early airway response, and another 11 volunteers early response followed by late
      airway response (dual response). Formate concentrations doubled 1 h post
      challenge in asthmatics with dual-airway response but essentially unchanged in
      patients with an isolated early reaction, CONCLUSIONS: Dual-airway response to
      allergen in atopic asthmatics could be associated with increased activity of S
      nitrosoglutathione reductase as suggested by greater concentrations of formate in
      exhaled breath condensate. Measurement of formate in exhaled breath condensate
      could serve as a noninvasive biomarker of S-nitrosoglutathione reductase activity
      in vivo. Our results need to be confirmed in a larger group of asthmatics.

PMID- 23557459
TI  - Assessment of long-term omalizumab treatment in patients with severe allergic
      asthma long-term omalizumab treatment in severe asthma.
AB  - OBJECTIVE: Several clinical studies have demonstrated the effectiveness of
      omalizumab in patients with severe allergic asthma but the treatment period has
      always been relatively short (4-12 months). In the literature, there are a few
      data about the long-term omalizumab therapy. We aimed to assess the long-term
      clinical and functional effectiveness of omalizumab treatment in severe allergic
      asthmatic patients, METHODS: Medical records describing the patients' status
      before the start of treatment, and also having been registered at the end of 4th,
      12th, and 36th months from the commencement of treatment, and at the last visit
      where the patient was evaluated were used for omalizumab effectiveness
      assessments. Twenty-six patients (female/male: 21/5) with severe allergic asthma,
      uncontrolled despite GINA 2006 Step 4 therapy, were included in the study.
      Effectiveness outcomes included spirometry measurements, level of asthma control
      measured by asthma control test (ACT), systemic glucocorticosteroid (sGCS) use,
      emergency room (ER) visits, and hospitalizations for severe exacerbations. In
      addition, the quality of life was assessed using the quality of life
      questionnaire AQLQ(S) before, 4, and 36 months after treatment, RESULTS: The mean
      age was 47.6 +/- 13.9 and duration of allergic asthma was 22.7 +/- 10.1 years.
      Serum total IgE levels were 322.0 +/- 178.1 IU/mL. Mean duration of omalizumab
      treatment was 40.81 +/- 8.2 months. FEV1 improved significantly at all control
      points versus baseline (p < .05). The level of asthma control as evaluated by ACT
      improved significantly after treatment (p < .05). We determined significantly
      reduced numbers of exacerbation, emergency visits, hospitalizations, sGCS, and
      SABA use by the end of 36 months (p < .05). The proportion of patients with
      improvements larger than 1.5 points in AQLQ(S) total score was 80.7% at the 4th
      month and 96.1% at the 36th month of treatment, CONCLUSIONS: This study showed
      that long-term therapy with omalizumab for up to 3 years was well tolerated with
      significant improvement both in symptoms and lung functions. Accordingly, long
      term omalizumab treatment may be recommended for responders.

PMID- 23557460
TI  - Genetic variation in the TNFA promoter region and TNFA gene expression in
      subjects with asthma.
AB  - OBJECTIVE: Asthma is a chronic disease that affects millions of people. Messenger
      RNA (mRNA) expression of specific inflammatory markers has been associated with
      asthma and corticosteroid response. Tumor necrosis factor-alpha (TNF-alpha), a
      pro-inflammatory cytokine, has been shown to have increased expression in airways
      of asthmatics and may be related to corticosteroid sensitivity. The purpose of
      this study was to determine how genetic variants within the promoter region of
      the TNFA gene differ between subjects with asthma and controls. We also
      investigated how genetic variation affects gene expression. METHODS: We enrolled
      94 subjects between 5 to 54 years of age who met the inclusion and exclusion
      criteria. TNFA mRNA expression was determined by qRT-PCR on total RNA isolated
      from the buccal mucosa. Genotyping was performed for TNFA-1031T/C, -857C/T, and 
      308G/A on genomic DNA isolated from blood with commercially available assays.
      Gene expression was log-2 transformed and corrected with 2 normalization genes.
      General linear model, Chi-square test, Fisher's exact test, and Cochran-Mantel
      Haenszel test were performed with p < .05. RESULTS: The TNFA-857C/T polymorphism
      is associated with asthma in this cohort. The TNFA-857 T allele is
      underrepresented in pediatric subjects with asthma relative to those without
      asthma (3% and 29% of individuals, respectively, p = .01). Furthermore, a TNFA
      haplotype combination containing -1031T/-857C/-308G and -1031T/-857T/-308G is
      associated with lower expression of TNF-alpha mRNA (p = .01) in pediatric
      subjects. CONCLUSIONS: Presence of the TNFA-857T allele may be protective in the
      development of asthma and a haplotype combination that contains the TNFA-857T
      allele is associated with TNFA expression.

PMID- 23557461
TI  - Signet-ring cell colon cancer in a 19-year-old patient with giant congenital
      cellular blue nevus of the scalp.

PMID- 23557463
TI  - Age-appropriate infant and young child feeding practices are associated with
      child nutrition in India: insights from nationally representative data.
AB  - Age-appropriate infant and young child feeding (IYCF) practices are critical to
      child nutrition. The objective of this paper was to examine the associations
      between age-appropriate IYCF practices and child nutrition outcomes in India
      using data from ~18 463 children of 0-23.9 months old from India's National
      Family Health Survey, 2005-06-3. The outcome measures were child height-for-age z
      score (HAZ), weight-for-age z-score (WAZ), weight-for-height z-score, stunting,
      underweight and wasting. Linear and logistic regression analyses were used,
      accounting for the clustered survey data. Regression models were adjusted for
      child, maternal, and household characteristics, and state and urban/rural
      residence. The analyses indicate that in India suboptimal IYCF practices are
      associated with poor nutrition outcomes in children. Early initiation of
      breastfeeding and exclusive breastfeeding were not associated with any of the
      nutrition outcomes considered. Not consuming any solid or semi-solid foods at 6
      8.9 months was associated with being underweight (P < 0.05). The diet diversity
      score and achieving minimum diet diversity (>=4 food groups) for children 6-23
      months of age were most strongly and significantly associated with HAZ, WAZ,
      stunting and underweight (P < 0.05). Maternal characteristics were also strongly
      associated with child undernutrition. In summary, poor IYCF practices,
      particularly poor complementary foods and feeding practices, are associated with
      poor child nutrition outcomes in India, particularly linear growth. 

PMID- 23557462
TI  - Substance use, risky sexual behaviors, and their associations in a Chinese sample
      of senior high school students.
AB  - BACKGROUND: Given the higher prevalence of risky sexual behaviors and substance
      use, adolescents and youths are at risk for HIV. Despite its importance, however,
      to the best of our knowledge, there are only a few researches on risky behaviors
      in Chinese adolescents/youths. The present study aimed to describe the prevalence
      of sexual and substance use behaviors among a Chinese sample of senior high
      school students. And more specifically, the associations of socio-demographic
      factors and substance use with risky sexual behaviors were examined in the
      sample. METHODS: A cross-sectional study was conducted in 10 senior high schools.
      A total of 2668 senior high school students aged 15.17 to 23.42 years
      participated in the survey. A self-administrated questionnaire was used to
      collect information on sexual and substance use behaviors. RESULTS: The
      percentages of students who ever had sexual intercourse in lifetime or during
      last three months were 7.0% and 5.1%, respectively. Among the participants with
      sexual intercourse during last three months, 42.1% ever had unprotected sexual
      intercourse and 49.4% had intercourse with two or more partners. Multivariate
      logistic regression analyses showed that cigarette smoke and illicit drug use
      were related to unprotected sexual intercourse (defined as "sexual intercourse
      without condom use") and younger age of first sexual intercourse was related to
      multiple-partner sexual intercourse. CONCLUSIONS: HIV/sexual transmitted
      infection (STI) health education and prevention are necessary among the Chinese
      adolescents, particularly among those adolescents with experience of sexual
      intercourse and/or substance use, which has a long-term beneficial to the control
      of HIV/STI in China.

PMID- 23557464
TI  - Product-dependent anti-factor VIII antibodies.
AB  - The development of anti-factor (F)VIII antibodies in haemophilia A (HA) subjects
      undergoing replacement therapy has been well documented. The correlation between
      antibody development and the FVIII product used for replacement therapy remains a
      subject of discussion. The aim of this study was to evaluate the presence of anti
      FVIII antibodies towards three commercial rFVIII products in 34 HA subjects'
      plasmas. Antibodies were quantitated by a Multiplex Fluorescence Immunoassay. All
      plasmas contained anti-FVIII antibodies at variable concentrations ranging from
      50 nm to 570 MUm. Eleven of the 20 HA subjects treated with one (r)FVIII product
      contained inhibitory anti-FVIII antibodies (0.8-3584 BU). The inhibitory antibody
      titre and the molar concentrations of total antibody were mildly correlated (r(2)
      = 0.6). Pronounced differences in antibody recognition with the three rFVIII
      products were observed. For the group treated with Product 'A', the titre towards
      this product was 2.4-fold higher than that observed with another full-length
      rFVIII-containing product (Product 'B') and almost four-fold higher than that
      measured with a B domain-less rFVIII product (Product 'C'). For the group of 14
      HA subjects treated with FVIII other than Product 'A', only one showed higher
      antibody titre when measured with this product. Our data suggest that the
      development of anti-FVIII antibodies is biased towards the product used for
      treatment and that a significant fraction of antibodies bind to the B domain of
      FVIII.

PMID- 23557466
TI  - The current state of knowledge, alongside recommendations for future research and
      practice.

PMID- 23557465
TI  - Entecavir for the treatment of patients with hepatitis B virus-related
      decompensated cirrhosis.
AB  - INTRODUCTION: Chronic hepatitis B (CHB) infection is common and carries a
      significant risk for the development of cirrhosis, hepatic decompensation, and
      hepatocellular carcinoma. The goal of treatment in patients with CHB-related
      decompensated cirrhosis is to improve hepatic dysfunction and reduce mortality
      through the inhibition of viral replication. Several studies have now shown
      nucleot(s)ide analogs to be safe and effective in decompensated cirrhosis due to
      CHB. AREAS COVERED: A review of the evidence for the use of entecavir in the
      treatment of decompensated hepatitis B cirrhosis is discussed. EXPERT OPINION:
      Entecavir is an effective treatment option for most patients with CHB. In
      treatment naive patients, it is a potent antiviral agent with a very low
      resistance rate, making it an excellent option for the treatment of decompensated
      hepatitis B cirrhosis. The use of entecavir monotherapy in patients with a known
      rtM204V lamivudine-resistant mutation should be avoided due to increased risk of
      developing entecavir resistance and failing treatment.

PMID- 23557467
TI  - Assessing the recommendations for the use of diagnostic imaging in clinical
      practice guidelines.
AB  - Accuracy is the primary evidence assessed when diagnostic imaging is evaluated in
      clinical practice guidelines. However, recommendations to not use diagnostic
      imaging are usually based not on its accuracy but on its lack of utility, that is
      its low Level 4 efficacy. If there is good clinical evidence that diagnostic
      imaging will not be useful in a clinical situation, the recommendation not to use
      it should be strong even if the evidence for its accuracy is of poor quality.

PMID- 23557468
TI  - Factors associated with nurses' perceptions of patient safety culture in China: a
      cross-sectional survey study.
AB  - OBJECTIVE: To explore nurses' perceptions of patient safety culture and factors
      associated with those perceptions. METHODS: This study used a quantitative
      methodology with a cross-sectional design. A convenience sample was used to
      recruit 248 nurses. Data were collected at a Chinese university hospital between
      August and October 2008. RESULTS: More than half (61.3%) of nurses had positive
      perceptions of patient safety culture. Nurses responded most positively to two
      dimensions: teamwork within units and organizational learning. Nurses responded
      most negatively to staffing and non-punitive response to errors. Four factors
      were found to be associated with patient safety culture: nurses' perception of
      managers' trustworthiness (P < 0.001), organizational safety prioritization (P <
      0.001), length of unit nursing experience (P = 0.004), and managers' safety
      commitment (P = 0.023). CONCLUSIONS: To improve patient safety culture, nurse
      managers should focus on the identified factors and adopt multiple strategies.
      Specifically, nurse mangers should try to build trust with nurses, demonstrate
      sincere safety commitments, and set patient safety as a true priority.

PMID- 23557469
TI  - Subject, function, and trend in medical ethics research: a comparative study of
      Chinese and non-Chinese literature using bibliometrics.
AB  - OBJECTIVE: To perform a comparative quantitative and qualitative analysis of
      Chinese and non-Chinese medical ethics literature using systematic research and
      literature analysis in order to discern research trends in the area and provide
      baseline data as a reference for relevant decision making and further study.
      METHOD: We retrieved articles using MeSH terms and keywords related to medical
      ethics in PubMed and CNKI, and then constructed a set of charts by applying word
      co-occurrence, The Pathfinder Networks algorithms, an included subject chart, a
      research field relationship chart, and strategy coordination charts. RESULT: The
      total of number of papers retrieved from PubMed was six times that retrieved from
      CNKI. Outside China, medical ethics has been studied in eight fully shaped
      subject fields, including morals, ethical review, physician-patient
      relationships, clinical trials, euthanasia, ethics education, clinical ethics,
      and health policy. In contrast, medical ethics research in China is still
      confined to five subject fields: morals, physician-patient relations, medical
      ethics education, ethical review, and medical research. CONCLUSION: Medical
      ethics research outside China emphasizes the application of medical ethics to
      solve emerging problems in clinical and medical research. It is mainly centered
      on morals, ethical review, and physician-patient relations. By comparison,
      medical ethics research in China places greater emphasis on morals and medical
      education. In order to narrow this gap between China and other countries, we
      should broaden the research scope of medical ethics and add more applied
      research, such as ethical review and medical education.

PMID- 23557470
TI  - A citation analysis of systematic review and meta-analysis published in Chinese
      journals.
AB  - BACKGROUND: The numbers of systematic reviews (SRs) and meta-analyses (MAs)
      published in China have dramatically increased in recent years. Comprehensive
      analysis of their citation status may prove beneficial to the production and
      integration of high quality research, thereby increasing the quality of medical
      policy-making, research, and clinical practice. METHODS AND FINDS: The Chinese
      Medical Citation Index (up to February 2010) was searched to identify SRs/MAs.
      Data were input using Microsoft Excel 2007 and statistical analysis was performed
      using SPSS 15.0 software. A total of 2224 SRs/MAs were included. Among the 591
      different publications distributed from 1994 to 2009, the median publication
      count per publication was two (1-270). The total citation count was 2796, with an
      average of 1.26 citations per publication (0-57 citation). SRs/MAs that were
      never cited amounted to 1380 papers (62.1%), distributed in 272 journals (46.0%).
      MAs were easier to find than SRs. The major conditions affecting citation were
      whether or not the report was published in a Western field (r = 0.287, P =
      0.000); whether or not the report was published in an "evidence-based" titled
      journal (r =-0.480, P = 0.002); and the length of time since publication (r =
      0.455, P = 0.000). Since 2004, publication of SRs/MAs has exhibited a downward
      trend, forming a negative correlation with publication count. CONCLUSIONS: Over
      half of the SRs/MAs included had never been cited by the time research had
      concluded. In many other cases these reports exhibited extremely low citation
      rates. Citation of traditional Chinese medicine SRs/MAs exceeded that of Western
      medicine studies. This indirectly suggests that the quality of SRs/MAs usage is
      relatively low in China. This may be a result of various reasons and suggests
      that emphasis should be placed on raising the quality of SRs/MAs and significance
      of practical application.

PMID- 23557471
TI  - Lessons learned from the Wenchuan earthquake.
AB  - OBJECTIVES: To conclude experience and lessons from emergency medical rescue
      after Wenchuan Earthquake from national and overall review for consideration on
      worldwide catastrophe rescue in the future. METHODS: To systematically collect
      huge amount of primary data, and to make analysis, draw conclusions and lessons
      in terms of five aspects respectively as quake-damage conditions, command system,
      emergency medical rescue, prevention and control over infectious diseases as well
      as pairing-assistance for medical system and service reconstruction. RESULTS: 1.
      Numbers as of the death, injured and migrants made Wenchuan Earthquake ranked one
      of the top 9 catastrophes around the world during the past two decades. 2.
      Countermeasures such as four-level linkage by nation-province-city-county model,
      mutual assistance between military force and local forces, frontline commanding
      did effectively ensure the dispatch and cooperation among rescue forces. 3. Three
      leveled medical transfers, "four concentrations" prevention and treatment besides
      whole-course rehabilitation at early stage managed to lower mortality and
      disability rate to minimum levels respectively. 4. "Four-keynote infectious
      disease control" under whole coverage and "five measures and four reinforcement
      measures" in settlements made rates as for those infectious diseases under the
      average level as those in the 3 pre-quake years. 5. Pairing-assistance in terms
      of talents, finance, materials as well as capacity building between other 18
      provinces/municipalities and those 18 extremely-stricken/severely-stricken areas
      in Sichuan Province guaranteed efficient post-quake reconstruction, system
      reconstruction and long-term mechanism construction. CONCLUSIONS: Successful
      experience from Wenchuan Earthquake could be summarized as: one goal as people
      oriented life-rescuing. Two tasks as medical rescue for diseases of those injured
      and healthcare & anti-epidemic for safe and sound of those lives. Three
      strategies respectively as medical transfers after on-site triage, treatment for
      severe diseases in quake-hit areas and rehabilitation in non quake-hit areas for
      medical rescue, and quick post-quake evaluation, quick promotion for whole
      coverage and scientific regulation in long term for healthcare & anti-epidemic.
      Four measures as concentration for patients, experts, resources and treatment
      respectively for medical rescue, and key regions, key groups, key infectious
      diseases and key steps for healthcare & anti-epidemic. Five links as overall
      commanding, medical rescue, healthcare and anti-epidemic, physical/mental
      rehabilitation and post-quake reconstruction. And whole course surveillance as
      information guidance, policy guarantee, data collection, evidence producing,
      effectiveness evaluation, and academic communication.

PMID- 23557472
TI  - Systematic reviews of TCM trials: how does inclusion of Chinese trials affect
      outcome?
AB  - AIM: Systematic reviews (SRs) are an important tool for the synthesis of research
      and are used to guide both research and clinical practice. Previous research
      suggests that changes to standard SR methodology may be warranted. The objectives
      of this study were to determine the value of adding Chinese-language databases to
      conventional systematic review (SR) search strategies, and ii) to determine the
      importance of methodological validation of TCM RCTs in the conduct of SRs of two
      health conditions, chronic fatigue syndrome (CFS) and EBV-infectious
      mononucleosis (mono). METHODS: Ten English-language and two Chinese-language
      databases were searched from inception to 2008. After initial screening
      potentially relevant publications were retrieved and assessed based on
      predetermined inclusion criteria. Method of randomization was verified using
      author interviews. RESULTS: Mono Search - While English-language database
      searches did not yield any potentially relevant references, Chinese-language
      database searches identified 14 studies labelled as RCTs. Author interview
      determined that 10 were clinical summaries and one a controlled clinical trial.
      Authors for three publications were unavailable. CFS Search - English-language
      and Chinese-language database searches identified 8 and 28 potentially relevant
      references, respectively, for a total of 36, however, none met all inclusion
      criteria. CONCLUSIONS: Utilization of Chinese-language databases greatly
      increased the number of potentially relevant references for each search.
      Unfortunately, due to methodological flaws, this additional information did not
      generate any usable information. Medical research in China continues to be
      active, including the conduct of RCTs, however, improvements in trial design and
      conduct in medical research in China are essential in order for this material to
      be useful in guiding research and practice.

PMID- 23557475
TI  - Four-year anniversary of Wenchuan earthquake: a disaster relief drill was held in
      Sichuan province.

PMID- 23557476
TI  - Education section--registration of systematic reviews.

PMID- 23557477
TI  - The role of arene-arene interactions in the folding of ortho-phenylenes.
AB  - The ortho-phenylenes are a simple class of helical oligomers and representative
      of the broader class of sterically congested polyphenylenes. Recent work has
      shown that o-phenylenes fold into well-defined helical conformations (in solution
      and, typically, in the solid state); however, the specific causes of this folding
      behavior have not been determined. Here, we report the effect of substituents on
      the conformational distributions of a series of o-phenylene hexamers. These
      experiments are complemented by dispersion-corrected DFT calculations on model
      oligomers (B97-D/TZV(2d,2p)). The results are consistent with a deterministic
      role for offset arene-arene stacking interactions on the folding behavior. On the
      basis of the experimental and computational results, we propose a model for o
      phenylene folding with two simple rules. (1) Conformers are forbidden if they
      include a particular sequence of biaryl torsional states that causes excessive
      steric strain. These "ABA" states correspond to consecutive dihedral angles of 
      55 degrees /+130 degrees /-55 degrees  (or +55 degrees /-130 degrees /+55). (2)
      The stability of the remaining conformers is determined by offset arene-arene
      stacking interactions that are easily estimated as an additive function of the
      number of well-folded torsional states (+/-55 degrees ) along the backbone. For
      the parent, unsubstituted poly(o-phenylene), each interaction contributes roughly
      0.5 kcal/mol to the helix stability (in chloroform), although their strength is
      sensitive to substituent effects. The behavior of the o-phenylenes as a class is
      discussed in the context of this model. They are analogous to alpha-helices, with
      axial aromatic stacking interactions in place of hydrogen bonding. The model
      predicts that the overall folding propensity should be quite sensitive to
      relatively small changes in the strength of the arene-arene stacking. In a
      broader sense, these results demonstrate that polyphenylenes may exhibit folding
      behavior that is amenable to simple models, and validate the use of diffusion
      corrected DFT methods in predicting their three-dimensional structures.

PMID- 23557478
TI  - Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case
      report.
AB  - DFSP is a locally invasive, slow-growing tumor of the subcutaneous tissue that
      rarely metastasizes but recurs frequently after surgical excision. We report
      herein a case of highly recurrent, locally invasive DFSP that failed both
      postoperative radiation therapy and complete trial of Imatinib, but was
      successfully treated with Sorafenib, which showed unprecedented response.

PMID- 23557479
TI  - Novel pebbles in the mosaic of autoimmunity.
AB  - Almost 25 years ago, the concept of the 'mosaic of autoimmunity' was introduced
      to the scientific community, and since then this concept has continuously
      evolved, with new pebbles being added regularly. We are now looking at an era in
      which the players of autoimmunity have changed names and roles. In this issue of
      BMC Medicine, several aspects of autoimmunity have been addressed, suggesting
      that we are now at the forefront of autoimmunity science. Within the
      environmental factors generating autoimmunity are now included unsuspected
      molecules such as vitamin D and aluminum. Some adjuvants such as aluminum are
      recognized as causal factors in the development of the autoimmune response. An
      entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants
      (ASIA), has been recently described. This is the new wind blowing within the
      branches of autoimmunity, adding knowledge to physicians for helping patients
      with autoimmune disease.

PMID- 23557480
TI  - Parent satisfaction with early and delayed abduction splinting therapy of
      developmental hip dysplasia.
AB  - AIM: To determine whether treatment for mild hip dysplasia instigated in the
      newborn period was preferred over a delayed treatment by the parents, as delayed
      treatment for mild hip dysplasia detected in newborns is an acceptable medical
      policy. METHODS: During a study period of 16 months from 2010 to 2011, parents
      attending the paediatric radiology outpatient clinic at Haukeland University
      Hospital for a follow-up of their baby with developmental dysplasia of the hip
      (DDH), were invited to fill in a questionnaire on parent satisfaction on
      information provided, and on follow-up and treatment given. RESULTS: A total of
      91 parents were included, of which 66 (72.5%) had their babies treated from birth
      (group 1), while 25 (27.5%) had their child treated from 5 weeks onwards (group
      2). Although parents in the delayed treatment group, in retrospect, were less
      satisfied with timing of the treatment than those in the early treatment group (p
      < 0.00), their general impression and total satisfaction did not differ (p =
      0.29). CONCLUSION: The overall parent satisfaction on follow-up and treatment did
      not differ according to whether treatment was instigated at birth or later in
      infancy.

PMID- 23557481
TI  - Structural and functional interactions of the prostate cancer suppressor protein
      NKX3.1 with topoisomerase I.
AB  - NKX3.1 (NK3 homeobox 1) is a prostate tumour suppressor protein with a number of
      activities that are critical for its role in tumour suppression. NKX3.1 mediates
      the cellular response to DNA damage by interacting with ATM (ataxia
      telangiectasia mutated) and by activation of topoisomerase I. In the present
      study we characterized the interaction between NKX3.1 and topoisomerase I. The
      NKX3.1 homeodomain binds to a region of topoisomerase I spanning the junction
      between the core and linker domains. Loss of the topoisomerase I N-terminal
      domain, a region for frequent protein interactions, did not affect binding to
      NKX3.1 as was shown by the activation of Topo70 (N-terminal truncated
      topoisomerase I) in vitro. In contrast, NKX3.1 interacts with the enzyme
      reconstituted from peptide fragments of the core and linker active site domains,
      but inhibits the DNA-resolving activity of the reconstituted enzyme in vitro. The
      effect of NKX3.1 on both Topo70 and the reconstituted enzyme was seen in the
      presence and absence of camptothecin. Neither NKX3.1 nor CPT (camptothecin) had
      an effect on the interaction of the other with topoisomerase I. Therefore the
      interactions of NKX3.1 and CPT with the linker domain of topoisomerase I are
      mutually exclusive. However, in cells the effect of NKX3.1 on topoisomerase
      binding to DNA sensitized the cells to cellular toxicity and the induction of
      apoptosis by low doses of CPT. Lastly, topoisomerase I is important for the
      effect of NKX3.1 on cell survival after DNA damage as topoisomerase knockdown
      blocked the effect of NKX3.1 on clonogenicity after DNA damage. Therefore NKX3.1
      and topoisomerase I interact in vitro and in cells to affect the CPT sensitivity
      and DNA-repair functions of NKX3.1.

PMID- 23557482
TI  - Economic evaluation of a lifestyle intervention in primary care to prevent type 2
      diabetes mellitus and cardiovascular diseases: a randomized controlled trial.
AB  - BACKGROUND: Cost-effectiveness studies of lifestyle interventions in people at
      risk for lifestyle-related diseases, addressing 'real-world' implementation, are
      needed. This study examines the cost-effectiveness of a primary care intervention
      from a societal perspective, compared with provision of health brochures,
      alongside a randomized controlled trial. METHODS: Adults aged 30-50 years, at
      risk of type 2 diabetes (T2DM) and/or cardiovascular disease (CVD), were
      recruited from twelve general practices in The Netherlands. They were randomized
      to the intervention (n = 314) or control group (n = 308). The intervention
      consisted of up to six face-to-face counseling sessions with a trained practice
      nurse, followed by three-monthly sessions by phone. Costs were collected using
      three-monthly retrospective questionnaires. Quality of life was measured with the
      EuroQol-5D-3L, at baseline, 6, 12 and 24 months. Nine-year risk of developing
      T2DM and ten-year risk of CVD mortality were estimated using the ARIC and SCORE
      formulae, respectively, based on measurements at baseline and 24 months while
      applying a fixed age of 60 years at both time points. RESULTS: Small,
      statistically non-significant differences in effects were found between the
      intervention and control group with regard to risk scores and Quality Adjusted
      Life Years (QALYs) gained. The mean difference in costs between the intervention
      and control group was ?-866 (95% confidence interval -2372; 370). The probability
      that the intervention was cost-effective varied from 93% at ?8000/QALY to 88% at
      ?80,000/QALY. CONCLUSION: A primary care lifestyle intervention aimed at adults
      at increased risk of T2DM and/or CVD could result in cost savings over a two-year
      period. However, due to methodological uncertainty no advice can be given
      regarding the implementation of the intervention in Dutch general practices.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN59358434.

PMID- 23557483
TI  - Nanophase hydroxyapatite as a biomaterial in advanced hard tissue engineering: a
      review.
AB  - Hydroxyapatite is a biocompatible material that is extensively used in the
      replacement and regeneration of bone material. In nature, nanostructured
      hydroxyapatite is the main component present in hard body tissues. Hence, the
      state of the art in nanotechnology can be exploited to synthesize nanophase
      hydroxyapatite that has similar properties with natural hydroxyapatite.
      Sustainable methods to mass-produce synthetic hydroxyapatite nanoparticles are
      being developed to meet the increasing demand for these materials and to further
      develop the progress made in hard tissue regeneration, especially for orthopedic
      and dental applications. This article reviews the current developments in
      nanophase hydroxyapatite through various manufacturing techniques and
      modifications. 

PMID- 23557485
TI  - A new arhythmacanthid species (Acanthocephala) in the intestine of Symphurus
      plagiusa and Ciclopsetta chittendeni from the coast of Campeche, Mexico, with
      ecological and histopathological observations.
AB  - A new species of Acanthocephaloides was recovered in the intestine of Symphurus
      plagiusa, the blackcheek tonguefish, and Cyclopsetta chittendeni, the Mexican
      flounder, from the Campeche coast, Mexico. The new species is characterized by
      having proboscis hooks arranged in 14 to 16 longitudinal rows, with 6-7 rooted
      hooks per row, a trunk covered with small cuticular spines (except in the zone of
      gonopore or bursa), a bursa without sensory structures, and the relative position
      of male post-equatorial reproductive system. The prevalence of Acanthocephaloides
      plagiusae n. sp. from S. plagiusa was low (0-7.3%) from July to October and high
      (29.4-40%) in November, January, and March. Similarly, the prevalence of A.
      plagiusae n. sp. from Cyclopsetta chittendeni was low (1.7%) in July and high
      (5.8%) March. Both hosts exhibited low (0.1-3.4) mean abundance. The variation in
      prevalence could be explained by the seasonal freshwater discharge from rivers,
      which affects the dispersal of parasites and the distribution of the host.
      Pathology changes, such as inflammation, loss of intestinal folds, increased
      mucous and rodlet cells, and detachment of intestinal epithelium, were associated
      with the proboscis hooks and spiny surface of A. plagiusae. This is the first
      record of an Acanthocephaloides species from a Mexican coastal zone.

PMID- 23557487
TI  - New analysis of the nu3 and nu4 bands of HNO3 in the 7.6 MUm region.
AB  - A new line position analysis of the nu3 and nu4 bands of nitric acid (HNO3) at
      1326.186 and 1303.072 cm(-1) together with its associated interacting bands is
      presented. The 3(1) and 4(1) energy levels were obtained from an extended
      analysis of high-resolution Fourier transform spectra recorded at Giessen in the
      7.6 MUm region. The energy levels of 3(1) and 4(1) upper states of nitric acid
      are strongly interacting with those of the 9(3), 6(2), 5(1)9(1), and 7(1)8(1)
      dark states centered at 1288.899, 1289.46, 1341.05, and 1343.78 cm(-1),
      respectively. Informations on these perturbing dark states were achieved through
      previous partial investigations of hot bands in high-resolution Fourier transform
      spectra recorded at 22 MUm in Giessen (for 3nu9-2nu9 and 3nu9-nu5), at 12 MUm in
      Denver (for 3nu9-nu9), and at 11 MUm in Orsay (for nu5+nu9-nu9). The energy
      levels calculation accounts for the various Fermi, anharmonic, A-type, B-type,
      and C-type Coriolis resonances, which couple together the
      {6(2),9(3),4(1),3(1),5(1)9(1),7(1)8(1)} interacting energy levels. For nitric
      acid, the nu9 mode (OH torsion relative to the -NO2 moiety) is a large amplitude
      motion. The theoretical model used in this work accounts also for large amplitude
      effects in the 9(3) dark state, which lead to a splitting of the 9(3) energy
      levels of about 0.060 cm(-1). In this way, the existence of torsional splittings
      for several nu4 perturbed lines was explained by the occurrence of local A-type
      and B-type Coriolis resonances coupling the 4(1) energy levels with those of
      9(3). Because four dark bands had to be accounted for in the model, the results
      of the energy level calculations are reasonable, although not perfect. However, a
      very significant improvement was achieved in terms of understanding the 7.6 MUm
      absorbing bands of nitric acid as compared to the analysis of the nu3 and nu4
      bands performed several years ago [Perrin, A.; Lado-Bordowski, O.; Valentin, A.
      Mol. Phys. 1989, 67, 249-267]. Finally, the present analysis also features, for
      the first time, the nu3+nu9-nu9 hot band located at 1331.09 cm(-1). This study
      will help to improve HNO3 measurements by satellites. This will be indeed the
      case for the "Infrared Atmospheric Sounding Interferometer" (IASI) experiment. 

PMID- 23557486
TI  - A diverted total syntheses of potent cell adhesion inhibitor peribysin E
      analogues.
AB  - Preliminary results from a program aimed at the creation of a focused library of
      analogues around the natural product peribysin E, a potent biologically active
      and structurally fascinating molecule, are reported. The total synthesis of (+/-)
      peribysin E was accomplished using a short route. Eight new analogues of the
      natural compound have been accomplished by means of "diverted total synthesis" in
      less than 10 steps. The present effort highlights protecting-group-free total
      syntheses and the shortest route to access these functionally embellished
      hydrindanes.

PMID- 23557488
TI  - Reconstruction of the biosynthetic pathway for the core fungal polyketide
      scaffold rubrofusarin in Saccharomyces cerevisiae.
AB  - BACKGROUND: Fungal polyketides include commercially important pharmaceuticals and
      food additives, e.g. the cholesterol-lowering statins and the red and orange
      monascus pigments. Presently, production relies on isolation of the compounds
      from the natural producers, and systems for heterologous production in easily
      fermentable and genetically engineerable organisms, such as Saccharomyces
      cerevisiae and Escherichia coli are desirable. Rubrofusarin is an orange
      polyketide pigment that is a common intermediate in many different fungal
      biosynthetic pathways. RESULTS: In this study, we established a biosynthetic
      pathway for rubrofusarin in S. cerevisiae. First, the Fusarium graminearum gene
      encoding polyketide synthase 12 (PKS12) was heterologously co-expressed with the
      Aspergillus fumigatus gene encoding phosphopantetheinyl transferase (npgA)
      resulting in production of YWA1. This aromatic heptaketide intermediate was
      converted into nor-rubrofusarin upon expression of the dehydratase gene aurZ from
      the aurofusarin gene cluster of F. graminearum. Final conversion into
      rubrofusarin was achieved by expression of the O-methyltransferase encoding gene
      aurJ, also obtained from the aurofusarin gene cluster, resulting in a titer of
      1.1 mg/L. Reduced levels of rubrofusarin were detected when expressing PKS12,
      npgA, and aurJ alone, presumably due to spontaneous conversion of YWA1 to nor
      rubrofusarin. However, the co-expression of aurZ resulted in an approx. six-fold
      increase in rubrofusarin production. CONCLUSIONS: The reconstructed pathway for
      rubrofusarin in S. cerevisiae allows the production of a core scaffold molecule
      with a branch-point role in several fungal polyketide pathways, thus paving the
      way for production of further natural pigments and bioactive molecules.
      Furthermore, the reconstruction verifies the suggested pathway, and as such, it
      is the first example of utilizing a synthetic biological "bottom up" approach for
      the validation of a complex fungal polyketide pathway.

PMID- 23557489
TI  - Epidural myelolipoma in a Husky-cross: a case report.
AB  - Epidural spinal myelolipoma was diagnosed in an 11.5-year-old castrated male
      Husky-cross that was evaluated at the veterinary teaching hospital due to
      progressive thoracolumbar spinal hyperaesthesia and mild proprioceptive pelvic
      limb ataxia. A focal, ill-defined mildly inhomogenous extradural mass lesion was
      detected by MRI. The dog was euthanized. At necropsy an extradurally located
      reddish mass of about 2.5 cm in diameter was present in the vertebral canal. The
      mass was identified histopathologically as an epidural myelolipoma.

PMID- 23557484
TI  - Invasive cells in animals and plants: searching for LECA machineries in later
      eukaryotic life.
AB  - Invasive cell growth and migration is usually considered a specifically metazoan
      phenomenon. However, common features and mechanisms of cytoskeletal
      rearrangements, membrane trafficking and signalling processes contribute to
      cellular invasiveness in organisms as diverse as metazoans and plants - two
      eukaryotic realms genealogically connected only through the last common
      eukaryotic ancestor (LECA). By comparing current understanding of cell
      invasiveness in model cell types of both metazoan and plant origin (invadopodia
      of transformed metazoan cells, neurites, pollen tubes and root hairs), we
      document that invasive cell behavior in both lineages depends on similar
      mechanisms. While some superficially analogous processes may have arisen
      independently by convergent evolution (e.g. secretion of substrate- or tissue
      macerating enzymes by both animal and plant cells), at the heart of cell invasion
      is an evolutionarily conserved machinery of cellular polarization and oriented
      cell mobilization, involving the actin cytoskeleton and the secretory pathway.
      Its central components - small GTPases (in particular RHO, but also ARF and Rab),
      their specialized effectors, actin and associated proteins, the exocyst complex
      essential for polarized secretion, or components of the phospholipid- and redox-
      based signalling circuits (inositol-phospholipid kinases/PIP2, NADPH oxidases)
      are aparently homologous among plants and metazoans, indicating that they were
      present already in LECA. REVIEWER: This article was reviewed by Arcady Mushegian,
      Valerian Dolja and Purificacion Lopez-Garcia.

PMID- 23557490
TI  - Self-reported questionnaire for surveillance of periodontitis in Chinese patients
      from a prosthodontic clinic: a validation study.
AB  - BACKGROUND AND PURPOSE: Periodontal maintenance is critical for the long-term
      success of prosthodontic treatment. This study investigates the validity of
      questionnaires/models in monitoring periodontitis for Chinese prosthodontic
      patients. METHODS: In total, 114 patients completed the questionnaire. The chi
      squared test and classification and regression trees were used to screen for
      predictive items. Predictive models developed by Yamamoto et al. and Dietrich et
      al. were validated using ROC curves and calibration plots. RESULTS: Univariate
      and multivariate analysis revealed that demographic features (age, gender,
      smoking history, education history and number of remaining teeth), symptoms(tooth
      mobility without injury, painful gums), dental recommendations ("need periodontal
      or gum treatment?") and treatment history (scaling and root planing) were
      predictive of periodontitis. The AUC values of the Yamamoto model and Dietrich's
      model-a and model-b were 0.67, 0.89, and 0.89 for moderate/severe periodontitis
      and 0.78, 0.93, and 0.93 for severe periodontitis, respectively. The calibration
      plot showed that Dietrich's model-a and model-b accurately predicted the actual
      probability of moderate/severe and severe periodontitis, respectively.
      CONCLUSION: Questionnaires may be an efficient approach to monitor periodontal
      health in China. Dietrich's models, with age, smoking and self-reported mobility
      as predictors, can be used to monitor periodontal health for Chinese
      prosthodontic patients.

PMID- 23557491
TI  - Women with scalp dysesthesia treated with pregabalin.

PMID- 23557492
TI  - Multicenter, double-blind, parallel group study investigating the non-inferiority
      of efficacy and safety of a 2% miconazole nitrate shampoo in comparison with a 2%
      ketoconazole shampoo in the treatment of seborrhoeic dermatitis of the scalp.
AB  - OBJECTIVES: This study investigated the non-inferiority of efficacy and tolerance
      of 2% miconazole nitrate shampoo in comparison with 2% ketoconazole shampoo in
      the treatment of scalp seborrheic dermatitis. METHODS: A randomized, double
      blind, comparative, parallel group, multicenter study was done. A total of 274
      patients (145 miconazole, 129 ketoconazole) were enrolled. Treatment was twice
      weekly for 4 weeks. Safety and efficacy assessments were made at baseline and at
      weeks 2 and 4. Assessments included symptoms of erythema, itching, scaling
      ['Symptom Scale of Seborrhoeic Dermatitis' (SSSD)], disease severity and global
      change [Clinical Global Impressions (CGIs) and Patient Global Impressions
      (PGIs)]. CONCLUSIONS: Miconazole shampoo is at least as effective and safe as
      ketoconazole shampoo in treating scalp seborrheic dermatitis scalp.

PMID- 23557493
TI  - Renin-angiotensin system inhibitors for prevention of recurrent atrial
      fibrillation: a meta-analysis.
AB  - INTRODUCTION: Conflicting results exist now on the clinical utility of renin
      angiotensin system (RAS) inhibitors in patients with atrial fibrillation (AF).
      This study aimed to elaborate the efficacy and safety of RAS blockade on
      preventing the relapse of AF by a meta-analysis based on randomised controlled
      trials (RCTs). METHODS: We searched Medline, ISI web of science and Cochrane
      databases through Jan 2012. We included RCTs comparing RAS inhibition treatment
      vs. placebo or alternative therapy after cardioversion of persistent AF or
      conventional medical therapy for paroxysmal AF and reporting outcome of recurrent
      AF. Odds ratios (OR) were calculated using a random effects model. RESULTS:
      Fifteen trials involving 3972 AF patients were included in the analysis. The
      pooling analysis showed that RAS inhibitors significantly reduced the recurrence
      of AF compared with non-RAS inhibitors (OR=0.50, 95% CI: 0.37-0.69, p<0.01), and
      the beneficial effect was shown consistently both in patients with paroxysmal and
      in those with persistent AF after cardoversion. However, administration of RAS
      inhibitors did not provide a greater survival advantage and a lower incidence of
      adverse effects than the control (OR=1.17, 95% CI, 0.65-2.10, p=0.59; OR=0.94,
      95% CI: 0.65-1.35, p=0.73 respectively). In addition, clinical factors
      potentially affecting AF relapsing had no pronounced impacts on the above
      clinical outcomes. CONCLUSIONS: Based on the currently available data, inhibition
      of RAS is effective, safe and well tolerated for preventing the recurrence of AF.

PMID- 23557494
TI  - Cat-scratch disease during anti-tumor necrosis factor-alpha therapy: case report
      and review of the literature.

PMID- 23557495
TI  - The contribution of office work to sedentary behaviour associated risk.
AB  - BACKGROUND: Sedentary time has been found to be independently associated with
      poor health and mortality. Further, a greater proportion of the workforce is now
      employed in low activity occupations such as office work. To date, there is no
      research that specifically examines the contribution of sedentary work to overall
      sedentary exposure and thus risk. The purpose of the study was to determine the
      total exposure and exposure pattern for sedentary time, light activity and
      moderate/vigorous physical activity (MVPA) of office workers during work and non
      work time. METHODS: 50 office workers from Perth, Australia wore an Actical
      (Phillips, Respironics) accelerometer during waking hours for 7 days (in 2008
      2009). Participants recorded wear time, waking hours, work hours and daily
      activities in an activity diary. Time in activity levels (as percentage of wear
      time) during work and non-work time were analysed using paired t-tests and
      Pearson's correlations. RESULTS: Sedentary time accounted for 81.8% of work hours
      (light activity 15.3% and MVPA 2.9%), which was significantly greater than
      sedentary time during non-work time (68.9% p < 0.001). Office workers experienced
      significantly more sustained sedentary time (bouts >30 minutes) and significantly
      less brief duration (0-10 minutes) light intensity activity during work hours
      compared to non-work time (p < 0.001). Further, office workers had fewer breaks
      in sedentary time during work hours compared to non-work time (p < 0.001).
      CONCLUSIONS: Office work is characterised by sustained sedentary time and
      contributes significantly to overall sedentary exposure of office workers.

PMID- 23557497
TI  - Editorial for issue 4 of 2012, Journal of Evidence Based Medicine.

PMID- 23557496
TI  - Successful percutaneous coronary intervention in a patient with combined
      deficiency of FV and FVIII due to novel compound heterozygous mutations in LMAN1.
AB  - Percutaneous coronary intervention (PCI) in patients with congenital coagulation
      factor deficiencies presents a unique challenge. They are not only at increased
      risk of perioperative bleeding but can also suffer thrombosis of the stent as
      preventive anticoagulation and antiplatelet therapy is difficult. Several cases
      of successful PCI have been described in patients with haemophilia A and B, but
      there are no reports in patients with combined coagulation factor deficiencies.
      We used PCI to treat the coronary artery disease in a patient with the combined
      deficiency of factor V and factor VIII (F5F8D) and analysed the molecular basis
      of the disorder for this patient. A 68-year-old patient was admitted for urgent
      PCI with bare metal stent placement after the diagnosis of the F5F8D. Peripheral
      blood DNA was extracted for the sequence analysis of LMAN1 and MCFD2 genes.
      Mutations in LMAN1 was confirmed by molecular cloning of the PCR product and
      resequencing of the resulting clones. The patient underwent successful PCI with
      good long-term outcome. Our patient tolerated anticoagulation therapy well, with
      unfractionated heparin, and double antiplatelet therapy while he was initially
      supported with fresh frozen plasma and recombinant FVIII. Molecular analysis
      revealed that the patient carries unusual compound heterozygous frameshift
      mutations on the same microsatellite repeat region in exon 8 of LMAN1, one of
      which is a novel mutation (c.912delA). Our results suggest that patients with
      F5F8D can safely undergo PCI for coronary artery disease, with the treatment
      individualized to the specific patient.

PMID- 23557498
TI  - Clinical trials and the public.

PMID- 23557499
TI  - Should measuring haemoglobin among chronic kidney disease patients be a
      performance measure?
AB  - OBJECTIVE: We attempted to: (1) to assess whether or not adequate evidence exists
      to advocate the measurement of anaemia in chronic kidney disease as a performance
      measure; and (2) to determine what the appropriate benchmarks might be for health
      systems seeking to implement this performance measure. DESIGN: Our study was
      conducted in two phases: (1) we used the United States Preventive Service Task
      Force chain of evidence methodology to determine six key questions that were
      subsequently reviewed to determine if adequate evidence existed to recommend
      haemoglobin testing among patients with chronic kidney disease; and (2) in order
      to establish a benchmark for a potential performance measure we measured the
      number of patients who had a test for anaemia during the preceding year and
      during the preceding three years. We established these benchmarks using chronic
      kidney disease defined both by estimated glomerular filtration rate and ICD-9
      codes. SETTING: Benchmarking was undertaken at Kaiser Permanente Northwest, which
      serves the Portland, Oregon and Vancouver, Washington metropolitan area, and
      Kaiser Permanente Georgia, which serves the Atlanta metropolitan area.
      PARTICIPANTS: Patients with chronic kidney disease identified by either estimated
      glomerular filtration rate or ICD-9 code. MAIN OUTCOMES MEASUREMENT: Serum
      haemoglobin INTERVENTION: This was an observational study. RESULTS: Our review of
      the evidence found no direct evidence that testing for anaemia among patients
      with chronic kidney disease improved patient morbidity or mortality. The ideal
      test for anaemia was serum haemoglobin. We found that available treatments of
      anaemia improve fatigue, but may increase mortality and stoke. We also found that
      an overwhelming majority of patients with chronic kidney disease defined by
      either estimated glomerular filtration rate or ICD-9 codes, over one or three
      years had had a haemoglobin measurement. CONCLUSION: There is currently
      inadequate evidence to recommend haemoglobin measurement among patients with
      chronic kidney disease as a performance measure. In addition, most patients with
      chronic kidney disease have already had haemoglobin measurement, minimizing the
      potential benefit of a performance measure.

PMID- 23557500
TI  - Preservative-free 0.9% sodium chloride for flushing and locking peripheral
      intravenous access device: a prospective controlled trial.
AB  - BACKGROUND AND AIM: In Mainland China, heparin saline solution is commonly used
      for flushing and locking peripheral intravenous access devices in clinical
      practice for a long time. We conducted a prospective controlled trial to compare
      the effectiveness and safety of preservative-free 0.9% sodium chloride solution
      versus heparin saline solution as flushing and locking solution for peripheral
      intravenous access devices. METHODS: Patients with gastroenterological or hepatic
      diseases were enrolled for this study from August 2011 to October 2011. After non
      randomized allocation, preservative-free 0.9% sodium chloride was used as
      flushing and locking solution in the sodium chloride solution group, while
      hepatic solution (10 U/mL) was given in the heparin saline solution group. The
      device related complications and its maintenance duration were compared between
      two groups. One-way ANOVA, Chi(2), or Mantel-Haenszel test were performed using
      SPSS 13.0 and RevMan 5.0. RESULTS: Totally, 181 and 178 peripheral intravenous
      access devices in the sodium chloride solution and heparin saline solution groups
      were included and analyzed. Results indicated than sodium chloride solution did
      not increase the risks of occlusion (7.7% vs. 7.9%) and other adverse events of
      peripheral intravenous access devices (P = 0.163). Sodium chloride solution
      neither shortened the duration of peripheral intravenous access devices
      maintenance (3.6 +/- 1.1 days vs. 3.7 +/- 1.2 days, P = 0.651), nor increased the
      proportion of abnormal withdrawal (29.3% vs. 31.5%, P = 0.654). CONCLUSION:
      Sodium chloride solution is as effective and safe as conventional heparin saline
      solution for flushing and locking peripheral intravenous access devices, which
      results from our evidence-based study and should be transferred to other nurses
      in China.

PMID- 23557501
TI  - Effect of ephedrine on intubating conditions created by propofol and rocuronium:
      a meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of ephedrine on intubation conditions (ICs) one
      minute after anesthesia induction using propofol and rocuronium. METHODS: PubMed,
      EMbase, The Cochrane Library, ISI Web of Knowledge, Chinese Biomedical Literature
      Database, Google Scholar, and other databases were searched from inception to
      September 2012 to collect relevant randomized clinical trials (RCTs). We
      evaluated the risk of bias of the included studies by the Cochrane
      Collaboration's risk of bias tool and analyzed the data using RevMan 5.1. As the
      outcomes, excellent ICs, clinically acceptable ICs and side effects were
      evaluated with risk ratios (RRs). RESULTS: Five RCTs involving 396 patients were
      identified. The results of the meta-analysis demonstrated that ephedrine
      increased the rate of excellent ICs (RR = 2.40, 95% CI 1.89 to 3.05), but had no
      effects on the rate of clinically acceptable ICs (RR = 1.15, 95% CI 0.93 to 1.42)
      and the incidence of side effects (RR = 2.00, 95% CI 0.19 to 21.36). Besides, the
      results of subgroup analysis showed that both low dose and high dose of ephedrine
      increased the rate of excellent ICs, but only low dose increased the rate of
      clinically acceptable ICs. The results of sensitive analysis showed that both
      favored ephedrine (excellent ICs: RR = 2.54, 95% CI 1.69 to 3.83; clinically
      acceptable ICs: RR = 1.21, 95% CI 1.07 to 1.38). CONCLUSION: Ephedrine, without
      extra side effects, created superior ICs one minute after anesthesia induction
      using propofol and rocuronium, and low dose (i.e., 70-100 MUg/kg) is recommended
      as the possible optimal dose.

PMID- 23557502
TI  - Effect of injection of brucea javanica oil emulsion plus chemoradiotherapy for
      lung cancer: a review of clinical evidence.
AB  - OBJECTIVE: Injection of brucea javanica oil emulsion (IBJOE), one of Chinese
      patent drugs has been widely used for lung cancer (LC) in China, and is known to
      provide some favorable outcomes, in particular when it combined with conventional
      treatment. However, little available best evidence is known about its effect and
      safety. This paper aims to evaluate the effectiveness and safety of IBJOE plus
      chemoradiotherapy to alleviate symptoms of LC patients. METHODS: A complete
      literature searching was conducted in databases including Chinese Biomedical
      Literature Database, China Academic Journals Full-text Database, Chinese
      Scientific Journals Database, the Cochrane Central Register of Controlled Trials,
      MEDLINE, and EMBASE to identify randomized controlled trials (RCTs) of IBJOE with
      chemoradiotherapy versus chemoradiotherapy alone for LC patients regardless of
      blinding, duration of treatment or duration of follow-up. All searching dates
      were from the beginning to December 2011. Quality of the included studies was
      assessed using the method by Cochrane Reviewer Handbook, and data analysis was
      performed using RevMan 5.10 software developed by The Cochrane Collaboration.
      RESULTS: The searching yielded over 1371 relevant citations, most of which did
      not meet the inclusion criteria. Finally, only 21 RCTs involving 1619 patients
      were included, and all the studies were of poor quality. Pooled analyses were
      performed to reveal that compared with chemoradiotherapy alone, IBJOE plus
      chemoradiotherapy had a better complete response rate (relative risk (RR) = 1.42;
      95% CI 1.05 to 1.92; P = 0.02) and improved quality of life (RR = 1.83; 95% CI
      1.63 to 2.07; P < 0.00001) measured by Karnofsky Performance Status scale. In
      addition, there was a significant difference on the outcome of long-term survival
      rate, level of immune function, and some incidences of adverse effects.
      CONCLUSIONS: IBJOE plus chemoradiotherapy may have positive effects on LC
      patients in response rate, improvement of quality of life, and reducing
      incidences of some adverse effects compared with chemoradiotherapy alone.
      However, the results need to be viewed with caution because of low quality of the
      included studies.

PMID- 23557503
TI  - Evidence-based practice curriculum in allied health professions for teaching
      research-practice nexus.
AB  - Allied healthcare workers are from diverse professions and the key skill required
      is providing evidence-based care but this concept has not permeated enough for
      using it skillfully in their professions. A well structured curriculum in allied
      health professions is needed to strengthen concerted teaching, research, and
      practice to empower their professionals and make considerable differences in the
      lives of people by adopting evidence-based practice. Information sources for
      allied health professionals have relied on advice of their supervisors and
      colleagues, personal experiences, authoritative theory and texts for practice.
      Because of "research-practice" gap, often the use of evidence is not reflected in
      an individual day to day professional practice. Although allied health
      professionals work in resource and evidence challenged settings, there are
      certain barriers and facilitators, which need to be addressed. To implement
      practice-related research findings and uptake of evidence requires two essential
      components, namely, practical component and knowledge component. Research bench
      marking and research metrics for quality assurance and standardization through
      evidence-based practice will promote academic status and credibility of allied
      health profession.

PMID- 23557504
TI  - Reporting 'number needed to treat' in meta-analyses: a cross-sectional study.
AB  - AIM: In translating clinical research into practice, the summarization of data
      from randomized trials in terms of measures of effect to be readily appreciated
      by the point-of-care clinicians is important. In this context, the body of
      literature highlighted the 'number needed to treat' as a useful measure. The
      objectives of our study were to assess how meta-analyses described number needed
      to treat and corresponding 95% CI, and to explore issues related to reporting
      number needed to treat in the selected meta-analyses. METHOD: For an
      illustration, we searched for the Cochrane systematic reviews and non-Cochrane
      systematic reviews. Two-stage selection was done to identify eligible studies.
      First, we fixed a date and then, we searched meta-analyses in PUBMED available on
      the date fixed. Secondly, we purposively selected five Cochrane systematic
      reviews and three non-Cochrane systematic reviews, according to our inclusion
      criteria. The critical appraisal of meta-analyses identified for the current
      study was done with the 5-item quality checklist introduced to the current
      analysis. RESULTS: A total of 8 systematic reviews, 5 Cochrane systematic reviews
      and 3 non-Cochrane systematic reviews/meta-analyses, were identified for the
      present study. Of these 8 meta-analyses, some (50%; 4/8) described number needed
      to treat in the method session of the study. However, the majority (87.5%; 7/8)
      reported number needed to treat in the results. For the details, 80% in Cochrane
      reviews and 66.5% in non-Cochrane reviews reported number needed to treat in the
      results. Only two studies (25%; 2/8) reported susceptibility to publication bias,
      provided simplified interpretation or discussed number needed to treat.
      CONCLUSION: Although the Cochrane handbook for systematic reviews of
      interventions suggests the reviewers to include number needed to treat in
      reporting effect estimations, there still is a need to improve.

PMID- 23557509
TI  - Caterpillar cereal as a potential complementary feeding product for infants and
      young children: nutritional content and acceptability.
AB  - Micronutrient deficiency is an important cause of growth stunting. To avoid
      micronutrient deficiency, the World Health Organization recommends complementary
      feeding with animal-source foods. However, animal-source foods are not readily
      available in many parts of the Democratic Republic of Congo (DRC). In such areas,
      caterpillars are a staple in adult diets and may be suitable for complementary
      feeding for infants and young children. We developed a cereal made from dried
      caterpillars and other locally available ingredients (ground corn, palm oil,
      sugar and salt), measured its macro- and micronutrient contents and evaluated for
      microbiologic contamination. Maternal and infant acceptability was evaluated
      among 20 mothers and their 8-10-month-old infants. Mothers were instructed in the
      preparation of the cereal and asked to evaluate the cereal in five domains using
      a Likert scale. Mothers fed their infants a 30-g portion daily for 1 week. Infant
      acceptability was based on cereal consumption and the occurrence of adverse
      events. The caterpillar cereal contained 132 kcal, 6.9-g protein, 3.8-mg iron and
      3.8-mg zinc per 30 g and was free from microbiologic contamination. Mothers'
      median ratings for cereal characteristics were (5 = like very much): overall
      impression = 4, taste = 5, smell = 4, texture = 4, colour = 5, and consistency =
      4. All infants consumed more than 75% of the daily portions, with five infants
      consuming 100%. No serious adverse events were reported. We conclude that a
      cereal made from locally available caterpillars has appropriate macro- and
      micronutrient contents for complementary feeding, and is acceptable to mothers
      and infants in the DRC. 

PMID- 23557510
TI  - The impact of staffing on central venous catheter-associated bloodstream
      infections in preterm neonates - results of nation-wide cohort study in Germany.
AB  - BACKGROUND: Very low birthweight (VLBW) newborns on neonatal intensive care units
      (NICU) are at increased risk for developing central venous catheter-associated
      bloodstream infections (CVC BSI). In addition to the established intrinsic risk
      factors of VLBW newborns, it is still not clear which process and structure
      parameters within NICUs influence the prevalence of CVC BSI. METHODS: The study
      population consisted of VLBW newborns from NICUs that participated in the German
      nosocomial infection surveillance system for preterm infants (NEO-KISS) from
      January 2008 to June 2009. Structure and process parameters of NICUs were
      obtained by a questionnaire-based enquiry. Patient based date and the occurrence
      of BSI derived from the NEO-KISS database. The association between the requested
      parameters and the occurrance of CVC BSI and laboratory-confirmed BSI was
      analyzed by generalized estimating equations. RESULTS: We analyzed data on 5,586
      VLBW infants from 108 NICUs and found 954 BSI cases in 847 infants. Of all BSI
      cases, 414 (43%) were CVC-associated. The pooled incidence density of CVC BSI was
      8.3 per 1,000 CVC days. The pooled CVC utilization ratio was 24.3 CVC-days per
      100 patient days. A low realized staffing rate lead to an increased risk of CVC
      BSI (OR 1.47; p=0.008) and also of laboratory-confirmed CVC BSI (OR 1.78;
      p=0.028). CONCLUSIONS: Our findings show that low levels of realized staffing are
      associated with increased rates of CVC BSI on NICUs. Further studies are
      necessary to determine a threshold that should not be undercut.

PMID- 23557511
TI  - On the influence of water on the electronic structure of firefly oxyluciferin
      anions from absorption spectroscopy of bare and monohydrated ions in vacuo.
AB  - A complete understanding of the physics underlying the varied colors of firefly
      bioluminescence remains elusive because it is difficult to disentangle different
      enzyme-lumophore interactions. Experiments on isolated ions are useful to
      establish a proper reference when there are no microenvironmental perturbations.
      Here, we use action spectroscopy to compare the absorption by the firefly
      oxyluciferin lumophore isolated in vacuo and complexed with a single water
      molecule. While the process relevant to bioluminescence within the luciferase
      cavity is light emission, the absorption data presented here provide a unique
      insight into how the electronic states of oxyluciferin are altered by
      microenvironmental perturbations. For the bare ion we observe broad absorption
      with a maximum at 548 +/- 10 nm, and addition of a water molecule is found to
      blue-shift the absorption by approximately 50 nm (0.23 eV). Test calculations at
      various levels of theory uniformly predict a blue-shift in absorption caused by a
      single water molecule, but are only qualitatively in agreement with experiment
      highlighting limitations in what can be expected from methods commonly used in
      studies on oxyluciferin. Combined molecular dynamics simulations and time
      dependent density functional theory calculations closely reproduce the broad
      experimental peaks and also indicate that the preferred binding site for the
      water molecule is the phenolate oxygen of the anion. Predicting the effects of
      microenvironmental interactions on the electronic structure of the oxyluciferin
      anion with high accuracy is a nontrivial task for theory, and our experimental
      results therefore serve as important benchmarks for future calculations.

PMID- 23557512
TI  - A qualitative study of primary care professionals' views of case finding for
      depression in patients with diabetes or coronary heart disease in the UK.
AB  - BACKGROUND: Routinely conducting case finding (also commonly referred to as
      screening) in patients with chronic illness for depression in primary care
      appears to have little impact. We explored the views and experiences of primary
      care nurses, doctors and managers to understand how the implementation of case
      finding/screening might impact on its effectiveness. METHODS: Two complementary
      qualitative focus group studies of primary care professionals including nurses,
      doctors and managers, in five primary care practices and five Community Health
      Partnerships, were conducted in Scotland. RESULTS: We identified several features
      of the way case finding/screening was implemented that may lead to systematic
      under-detection of depression. These included obstacles to incorporating case
      finding/screening into a clinical review consultation; a perception of replacing
      individualised care with mechanistic assessment, and a disconnection for nurses
      between management of physical and mental health. Far from being a standardised
      process that encouraged detection of depression, participants described case
      finding/screening as being conducted in a way which biased it towards negative
      responses, and for nurses, it was an uncomfortable task for which they lacked the
      necessary skills to provide immediate support to patients at the time of
      diagnosis. CONCLUSION: The introduction of case finding/screening for depression
      into routine chronic illness management is not straightforward. Routinized case
      finding/screening for depression can be implemented in ways that may be
      counterproductive to engagement (particularly by nurses), with the mental health
      needs of patients living with long term conditions. If case finding/screening or
      engagement with mental health problems is to be promoted, primary care nurses
      require more training to increase their confidence in raising and dealing with
      mental health issues and GPs and nurses need to work collectively to develop the
      relational work required to promote cognitive participation in case
      finding/screening.

PMID- 23557514
TI  - Transition to noncurative end-of-life care in paediatric oncology--a nationwide
      follow-up in Sweden.
AB  - AIM: To estimate whether and when children dying from a malignancy are recognized
      as being beyond cure and to study patterns of care the last weeks of life.
      METHODS: A nationwide retrospective medical record review was conducted. Medical
      records of 95 children (60% of eligible children) who died from a malignancy 2007
      2009 in Sweden were studied. RESULTS: Eighty-three children (87%) were treated
      without curative intent at the time of death. Children with haematological
      malignancies were less likely to be recognized as being beyond cure than children
      with brain tumours [relative risks (RR) 0.7; 95% confidence interval (CI) 0.6
      0.9] or solid tumours (RR 0.8; 0.6-1.0). The transition to noncurative care
      varied from the last day of life to over four years prior to death (median 60
      days). Children with haematological malignancies were treated with a curative
      intent closer to death and were also given chemotherapy (RR 5.5; 1.3-22.9),
      transfusions (RR 2.0; 1.0-4.0) and antibiotics (RR 5.3; 1.8-15.5) more frequently
      than children with brain tumours the last weeks of life. CONCLUSION: The majority
      of children dying from a malignancy were treated with noncurative intent at the
      time of death. The timing of a transition in care varied with the diagnoses,
      being closer to death in children with haematological malignancies.

PMID- 23557513
TI  - Biologic therapy for autoimmune diseases: an update.
AB  - Biologic therapies for rheumatologic diseases, which are targeted at molecules
      involved in the mechanisms of the immune system, provide an alternative to the
      existing treatment methods of disease-modifying anti-rheumatic drugs and other
      immunosuppressive medications. However, the current drawbacks of biologic
      therapies, including the inconvenience of intravenous administration, the high
      costs of these drugs, and the adverse events associated with them, prevent their
      wide use as first-line medications. This review provides an update of the recent
      literature on the new biologic therapies available. The review concentrates on
      nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab,
      abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies
      for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus,
      systemic sclerosis, or vasculitis.

PMID- 23557515
TI  - Reactive uptake and photo-Fenton oxidation of glycolaldehyde in aerosol liquid
      water.
AB  - The reactive uptake and aqueous oxidation of glycolaldehyde were examined in a
      photochemical flow reactor using hydrated ammonium sulfate (AS) seed aerosols at
      RH = 80%. The glycolaldehyde that partitioned into the aerosol liquid water was
      oxidized via two mechanisms that may produce aqueous OH: hydrogen peroxide
      photolysis (H2O2 + hnu) and the photo-Fenton reaction (Fe (II) + H2O2 + hnu). The
      uptake of 80 (+/-10) ppb glycolaldehyde produced 2-4 wt % organic aerosol mass in
      the dark (kH* = (2.09-4.17) * 10(6) M atm(-1)), and the presence of an OH source
      increased the aqueous uptake by a factor of 4. Although the uptake was similar in
      both OH-aging mechanisms, photo-Fenton significantly increased the degree of
      oxidation (O/C = 0.9) of the aerosols compared to H2O2 photolysis (O/C = 0.5).
      Aerosol organics oxidized by photo-Fenton and H2O2 photolysis resemble ambient
      "aged" and "fresh" OA, respectively, after the equivalent of 2 h atmospheric
      aging. No uptake or changes in particle composition occurred on dry seed aerosol.
      This work illustrates that photo-Fenton chemistry efficiently forms highly
      oxidized organic mass in aerosol liquid water, providing a possible mechanism to
      bridge the gap between bulk-phase experiments and ambient particles.

PMID- 23557516
TI  - Positive mood boosts the expression of a dispositional need for closure.
AB  - Three studies (N=539) examined the hypothesis that positive mood increases the
      degree to which epistemic motivation, i.e., the need for closure (NFC), affects
      the way in which an individual processes information (heuristic vs. systematic
      processing). In each of the studies, different methods of operationalising mood
      were used: in Study 1, mood was measured as a state; in Study 2, mood was induced
      by asking participants to recall emotional events; and in Study 3, mood was
      induced by emotional pictures. The styles of information processing that were
      utilised by our participants were operationalised in terms of their preferences
      for (Study 1) and ability to recall (Studies 2 and 3) schema-consistent and
      schema-inconsistent information. Taken together, the results of the three studies
      show that only under positive mood, NFC level of an individual is consistent with
      his or her style of information processing, that is, only under positive mood is
      there a negative relationship between the NFC level of an individual and the
      utilisation of schema-inconsistent information. Our results can be explained in
      terms of the effect that mood has on an individual's perceived ability to achieve
      NFC. 

PMID- 23557517
TI  - Characterization of a novel HLA-DQB1*06 allele, HLA-DQB1*06:04:04.
AB  - The novel allele human leukocyte antigen(HLA)-DQB1*06:04:04 differs from HLA
      DQB1*06:04:01 by a silent nucleotide substitution at codon 75 (TTG -> CTG).

PMID- 23557518
TI  - Ternatusine A, a new pyrrole derivative with an epoxyoxepino ring from Ranunculus
      ternatus.
AB  - Ternatusine A (1), a novel alkaloid with an unprecedented epoxyoxepino[4,5-c]
      pyrrole ring, was isolated from the roots of Ranunculus ternatus Thunb. Its
      unusual structure, including its absolute stereochemistry, was determined using
      UV, IR, HRESIMS, and 1D and 2D NMR data and through comparison of the
      experimental and calculated electronic circular dichroism (ECD) spectra. A
      possible biosynthetic pathway for ternatusine A was postulated.

PMID- 23557521
TI  - Editorial for Issue 1 of 2013, Journal of Evidence-Based Medicine.

PMID- 23557520
TI  - Successful treatment of rheumatoid vasculitis-associated skin ulcer with a TNF
      alpha antagonist.

PMID- 23557519
TI  - Practical use of dabigatran etexilate for stroke prevention in atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is associated with an increased risk of thromboembolism,
      and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists
      (VKAs) have been the standard of care for stroke prevention in patients with AF
      since the early 1990s. They are very effective for the prevention of
      cardioembolic stroke, but are limited by factors such as drug-drug interactions,
      food interactions, slow onset and offset of action, haemorrhage and need for
      routine anticoagulation monitoring to maintain a therapeutic international
      normalised ratio (INR). Multiple new oral anticoagulants have been developed as
      potential replacements for VKAs for stroke prevention in AF. Most are small
      synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa
      (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have
      predictable pharmacokinetics that allow fixed dosing without routine laboratory
      monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to
      be approved by the United States Food and Drug Administration and the European
      Medicines Agency for stroke prevention in patients with non-valvular AF,
      represents an effective and safe alternative to VKAs. Under the auspices of the
      Regional Anticoagulation Working Group, a multidisciplinary group of experts in
      thrombosis and haemostasis from Central and Eastern Europe, an expert panel with
      expertise in AF convened to discuss practical, clinically important issues
      related to the long-term use of dabigatran for stroke prevention in non-valvular
      AF. The practical information reviewed in this article will help clinicians make
      appropriate use of this new therapeutic option in daily clinical practice.

PMID- 23557522
TI  - Introduction to the new column of the BRICS Medicines Alliance.

PMID- 23557523
TI  - Pediatric off-label drug use in China: risk factors and management strategies.
AB  - OBJECTIVE: To analyze the risk factors of pediatric off-label drug use, and
      propose management strategies for policy making of the pediatric off-label drug
      use in China. METHODS: (i) We applied stratified random sampling to select
      recipes of children aged 0 to 18 years in pediatric clinics and wards of the West
      China Second University Hospital in 2010. (ii) All included prescriptions were
      categorized as off-label use or on-label use, according to the latest package
      insert licensed by the State Food and Drug Administration. (iii) Risk factors and
      the weights were calculated using logistic regression. (iv) The correlation
      between risk factors and the different kinds of off-label prescriptions was
      presented using adjusted odds ratio, and the impact of the risk factors was
      measured using standardized partial regression coefficient. (v) SPSS 16.0 was
      used for statistic analysis. (vi) From the perspective of the medical
      institutions, pharmaceutical enterprises, professional institutions, and the
      public, we combined the results of the Evidence-based research on the policy of
      the off-label drug use in 15 countries and the results of risk factor analysis,
      in order to propose management strategies for the policy making of pediatric off
      label drug use in China. RESULTS: (i) Using the method of sampling, we received
      2640 recipes from outpatients and 14,374 prescriptions from 749 inpatients. (ii)
      The neonates (0 to 27 days) had higher risk in off-label drug use than the other
      three children age groups. (iii) The dermatological medicines (D), nervous system
      medicines (N), traditional Chinese medicines, and respiratory drugs (R) were high
      risk off-label medicines whose labels should be updated more frequently. (iv) The
      great factors of off-label drug use are those influence health status and relate
      to health services (ICD-10:Z00-Z99) (mainly in the clinic of child care and
      growth development, and in the ward of chemotherapy). (v) Off-label drug use in
      the ward was 4.4 times than that in clinic service (P < 0.001), which suggested
      that off-label drug use in the ward may be a key point of the management of
      medical institutions. (vi) The risk of off-label essential drug use was 1.67
      times than that of non-essential drug use. (vii) The risk of off-label Rx drug
      use was 3.2% higher than that of OTC (Over-The-Counter) drug use, without a
      significant difference. CONCLUSIONS: (i) A management guideline for off-label
      drug use is urgently needed, with which we can guide medical institutions to
      establish the management regulations of off-label drug use. (ii) Pediatric
      clinical research should be promoted actively, and pharmaceutical enterprises
      should be encouraged to completely provide pediatric drug information. (iv)
      Academic organizations should be invited to join in for best professional drug
      use. (v) Pediatric patients and their families should receive the education on
      rational drug use.

PMID- 23557524
TI  - Challenges for clinical medical education in China.

PMID- 23557525
TI  - Challenges and a response strategy for the development of nursing in China: a
      descriptive and quantitative analysis.
AB  - OBJECTIVE: To assess the challenges to and provide a response strategy for the
      development of nursing and make suggestions for promoting the nursing discipline,
      platform, and talent teams based on current best available evidence. METHODS: We
      searched CNKI(China National Knowledge Infrastructure), VIP information(Chinese
      Scientific Journals database), CBM(Chinese Biomedical Literature database), and
      Web sites of the World Health Organization, International Council of Nurses,
      World Bank, the Ministry of Health and the Ministry of Education of China, and
      relevant schools in China. Data analyses were performed using SPSS 13.0. RESULTS:
      We identified 886 nursing schools in China in 2012. Results showed that 38,212
      nursing students were enrolled in universities or independent colleges and
      130,837 nursing student were enrolled in colleges or senior vocational schools.
      The doctor-to-nurse ratio was 1:0.9 in 2010. The actual demand for doctors was
      2.6 million, whereas the nursing shortage was approximately 346,000. Nurses aged
      <= 35 years accounted for 50% of the total. A total of 64% to 69% of nurses had
      primary professional titles; fewer than 2.5% of those had advanced titles. The
      training costs for one doctor or one nurse in China was only two-fifths that in
      India and one-fifth to one-fourth that in sub-Saharan Africa. To date, only 30.1%
      of disaster nursing studies in China provided research data; 30.6% were related
      to clinical experience and 38.3% were reviews. CONCLUSIONS: Education and health
      systems need to be extensively reformed. It is necessary to train nursing
      students with core competencies using transformative learning. It is necessary to
      update textbooks and teaching methods, and funding should be appropriately
      increased. Nursing should co-operate with other disciplines, and apply evidence
      based nursing methods to improve the quality of healthcare services and patient
      satisfaction.

PMID- 23557526
TI  - Visualization of evidence-based medicine domain knowledge: production and
      citation of Cochrane systematic reviews.
AB  - OBJECTIVES: To evaluate the production and utilization of Cochrane systematic
      reviews (CSRs) and to analyze its influential factors, so as to improve the
      capacity of translating CSRs into practice. METHODS: All CSRs and protocols were
      retrieved from the Cochrane Library (Issue 2, 2011) and citation data were
      retrieved from SCI database. Citation analysis was used to analyze the situation
      of CSRs production and utilization. RESULTS: CSR publication had grown from an
      annual average of 32 to 718 documents. Only one developing country was among the
      ten countries with the largest amount of publications. High-income countries
      accounted for 83% of CSR publications and 90.8% of cited counts. A total 34.7% of
      CSRs had a cited count of 0, whereas only 0.9% had been cited more than 50 times.
      Highly cited CSRs were published in England, Australia, Canada, USA and other
      high-income countries. The countries with a Cochrane center or a Cochrane
      methodology group had a greater capability of CSRs production and citing than
      others. The CSRs addressing the topics of diseases were more than those targeted
      at public health issues. There was a big gap in citations of different
      interventions even on the same topic. CONCLUSIONS: The capability of CSR
      production and utilization grew rapidly, but varied among countries and
      institutions, which was affected by several factors such as the capability of
      research, resources and the applicability of evidence. It is important to improve
      evidence translation through educating, training and prioritizing the problems
      based on real demands of end users.

PMID- 23557527
TI  - Literature review regarding patient safety culture.
AB  - BACKGROUND: Quite a number of articles on patient safety culture have been
      published in recent 10 years to assess the safety culture in hospitals using the
      Hospital Survey on Patient Safety Culture in many countries. However, until now
      there have been no relevant studies to investigate the quality of these, and
      their contribution to present-day thinking. OBJECTIVES: The aim of this study was
      to explore the areas of theme, and the study design of published research on
      patient safety culture in literature published in English and Chinese language
      journals. METHODS: We searched the major databases, including MEDLINE, EMbase,
      Chinese Biomedical Literature Database, Chinese Journals Full-text Database, and
      to analyze the publication years, research themes, authors' affiliations and
      methodologies of articles published from January 2001 to December 2011. Quality
      and statistical method were only appraised by classification of study designs.
      RESULTS: The annual number of published articles on patient safety culture was
      increasing in the last decade, and the number of articles published in 2010 and
      2011 reached its peak with 86 articles accounting for 44.6% of the decade's
      publication; patient safety culture scale dominated the included literature,
      accounting for 67.8% of all studies. Cross-sectional studies and commentary
      reviews were the most popular study designs which took up approximately 95.9% of
      the included studies with 66.9% (129 articles) and 29.0% (56 articles),
      respectively. All the included studies on patient safety culture were conducted
      in the following four institutions: hospitals, geracomium, Veterans Health
      Administration hospitals, and medical schools. CONCLUSIONS: There is a growing
      change trend in the number of articles on patient safety culture research in
      recent 10 years, most of which are non-comparative studies. More methodologically
      rigorous designs are needed to improve research quality on patient safety
      culture.

PMID- 23557533
TI  - Education section--reporting of randomised trials.

PMID- 23557528
TI  - Understanding GRADE: an introduction.
AB  - OBJECTIVE: Grading of recommendations, assessment, development, and evaluations
      (GRADE) is arguably the most widely used method for appraising studies to be
      included in systematic reviews and guidelines. In order to use the GRADE system
      or know how to interpret it when reading reviews, reading several articles and
      attending a workshop are required. Moreover, the GRADE system is not covered in
      standard medical textbooks. Here, we explain GRADE concisely with the use of
      examples so that students and other researchers can understand it. BACKGROUND: In
      order to use or interpret the GRADE system, reading several articles and
      attending a workshop is currently required. Moreover, the GRADE system is not
      covered in standard medical textbooks. METHODS: We read, synthesized, and
      digested the GRADE publications and contacted GRADE contributors for explanations
      where required. We composed a digested version of the system in a concise way a
      general medical audience could understand. RESULTS: We were able to explain the
      GRADE basics clearly and completely in under 1500 words. CONCLUSIONS: While
      advanced critical appraisal requires judgment, training, and practice, it is
      possible for a non-specialist to grasp GRADE basics very quickly.

PMID- 23557535
TI  - Facial verrucous sporotrichosis in an adult during treatment for rosacea.

PMID- 23557536
TI  - Carbamoyl anion addition to N-sulfinyl imines: highly diastereoselective
      synthesis of alpha-amino amides.
AB  - Carbamoyl anions, generated from N,N-disubstituted formamides and lithium
      diisopropylamide, add with high diastereoselectivity to chiral N-sulfinyl
      aldimines and ketimines to provide alpha-amino amides. The methodology enables
      the direct introduction of a carbonyl group without the requirement of unmasking
      steps as with other nucleophiles. The products may be converted to alpha-amino
      esters or 1,2-diamines. Iterative application of the reaction enabled the
      stereoselective synthesis of a dipeptide. Spectroscopic and computational studies
      support an anion structure with eta(2) coordination of lithium by the carbonyl
      group.

PMID- 23557537
TI  - Fabrication of electrospun poly(L-lactide-co-epsilon-caprolactone)/collagen
      nanoyarn network as a novel, three-dimensional, macroporous, aligned scaffold for
      tendon tissue engineering.
AB  - Tissue engineering techniques using novel scaffolding materials offer potential
      alternatives for managing tendon disorders. An ideal tendon tissue engineered
      scaffold should mimic the three-dimensional (3D) structure of the natural
      extracellular matrix (ECM) of the native tendon. Here, we propose a novel
      electrospun nanoyarn network that is morphologically and structurally similar to
      the ECM of native tendon tissues. The nanoyarn, random nanofiber, and aligned
      nanofiber scaffolds of a synthetic biodegradable polymer, poly(L-lactide-co
      epsilon-caprolactone) [P(LLA-CL)], and natural collagen I complex were fabricated
      using electrospinning. These scaffolds were characterized in terms of fiber
      morphology, pore size, porosity, and chemical and mechanical properties for the
      purpose of culturing tendon cells (TCs) for tendon tissue engineering. The
      results indicated a fiber diameter of 632 +/- 81 nm for the random nanofiber
      scaffold, 643 +/- 97 nm for the aligned nanofiber scaffold, and 641 +/- 68 nm for
      the nanoyarn scaffold. The yarn in the nanoyarn scaffold was twisted by many
      nanofibers similar to the structure and inherent nanoscale organization of
      tendons, indicating an increase in the diameter of 9.51 +/- 3.62 MUm. The
      nanoyarn scaffold also contained 3D aligned microstructures with large
      interconnected pores and high porosity. Fourier transform infrared analyses
      revealed the presence of collagen in the three scaffolds. The mechanical
      properties of the sample scaffolds indicated that the scaffolds had desirable
      mechanical properties for tissue regeneration. Further, the results revealed that
      TC proliferation and infiltration, and the expression of tendon-related ECM
      genes, were significantly enhanced on the nanoyarn scaffold compared with that on
      the random nanofiber and aligned nanofiber scaffolds. This study demonstrates
      that electrospun P(LLA-CL)/collagen nanoyarn is a novel, 3D, macroporous, aligned
      scaffold that has potential application in tendon tissue engineering.

PMID- 23557538
TI  - Metabolic syndrome and periodontitis in Gullah African Americans with type 2
      diabetes mellitus.
AB  - AIM: To assess associations of metabolic syndrome, and its individual components,
      with extent of severe periodontitis among patients with type 2 diabetes mellitus
      (T2DM). MATERIALS & METHODS: We performed a secondary data analysis (N = 283)
      using a cross-sectional study population of Gullah African Americans with T2DM.
      Extent of severe periodontitis was assessed as total diseased tooth-sites/person
      [evaluated as separate outcomes: 6+mm clinical attachment level (CAL), 5+mm
      periodontal probing depth (PPD)] using negative binomial regression techniques.
      Primary independent variables assessed in separate models included metabolic
      syndrome (yes/no), each metabolic syndrome component (low HDL, hypertension, high
      triglycerides, large waist circumference) and glycemic control (poor/good).
      RESULTS: Multivariable CAL-model results showed a significant association for
      metabolic syndrome status with extent of severe periodontitis (RR = 2.77, p =
      0.03). The separate multivariable CAL-model including each metabolic syndrome
      component showed marginally increased rates among those with large waist
      circumference (RR = 2.33, p = 0.09) and those with HbA1c >= 7% (RR = 1.73, p =
      0.06). Multivariable PPD-models showed marginally increased rates among those
      with metabolic syndrome (RR = 2.18, p = 0.06). CONCLUSION: Metabolic syndrome is
      associated with the extent of severe periodontitis in this Gullah population with
      T2DM.

PMID- 23557539
TI  - Difficult-to-detect carbapenem-resistant IMP13-producing P. aeruginosa:
      experience feedback concerning a cluster of urinary tract infections at a
      surgical clinic in France.
AB  - BACKGROUND: We report a carbapenem-resistant P. aeruginosa clone responsible for
      a cluster of urinary tract infections in elderly surgery patients, diagnosed
      during a three-month period in a 59-bed surgical clinic. FINDINGS: The clonal
      nature of the cluster was established by molecular study of the P. aeruginosa
      isolates (PFGE and MLST). Despite an MIC of imipenem in the susceptibility range
      for two isolates, all were metallo-beta-lactamase-producers (IMP13-type, clone
      ST621). We conducted a review of the medical and surgical procedures. We tested
      water delivered into the clinic and urological devices for the presence of the
      epidemic strain. The hygiene nurse observed hygiene practices. A week after the
      implementation of barrier precautions around the fourth infected patient, we
      studied the extent to which the patients hospitalised were colonised to assess
      whether the spread of the epidemic strain had been controlled. CONCLUSIONS: 1/
      Our findings indicate the difficulties in the detection of the metallo-beta
      lactamase in this clone, that resulted in the alert being delayed. 2/ Unlike most
      investigations of UTI outbreaks described in urology wards, we did not detect any
      contaminated urological devices or water colonisation. 3/ Consistent with
      outbreaks involving the IMP-13 clone in critical care units, the observation of
      inadequate application of standard precautions argued for patient-to-patient
      transmission during urinary management of the urology patients. 4/ The
      implementation of barrier precautions around infected patients resulted in
      control of the spread of the epidemic clone. This report serves as an alert
      concerning a difficult-to-detect multidrug-resistant P. aeruginosa clone in
      elderly urology patients.

PMID- 23557541
TI  - A density-functional theory-based neural network potential for water clusters
      including van der Waals corrections.
AB  - The fundamental importance of water for many chemical processes has motivated the
      development of countless efficient but approximate water potentials for large
      scale molecular dynamics simulations, from simple empirical force fields to very
      sophisticated flexible water models. Accurate and generally applicable water
      potentials should fulfill a number of requirements. They should have a quality
      close to quantum chemical methods, they should explicitly depend on all degrees
      of freedom including all relevant many-body interactions, and they should be able
      to describe molecular dissociation and recombination. In this work, we present a
      high-dimensional neural network (NN) potential for water clusters based on
      density-functional theory (DFT) calculations, which is constructed using clusters
      containing up to 10 monomers and is in principle able to meet all these
      requirements. We investigate the reliability of specific parametrizations
      employing two frequently used generalized gradient approximation (GGA) exchange
      correlation functionals, PBE and RPBE, as reference methods. We find that the
      binding energy errors of the NN potentials with respect to DFT are significantly
      lower than the typical uncertainties of DFT calculations arising from the choice
      of the exchange-correlation functional. Further, we examine the role of van der
      Waals interactions, which are not properly described by GGA functionals.
      Specifically, we incorporate the D3 scheme suggested by Grimme (J. Chem. Phys.
      2010, 132, 154104) in our potentials and demonstrate that it can be applied to
      GGA-based NN potentials in the same way as to DFT calculations without
      modification. Our results show that the description of small water clusters
      provided by the RPBE functional is significantly improved if van der Waals
      interactions are included, while in case of the PBE functional, which is well
      known to yield stronger binding than RPBE, van der Waals corrections lead to
      overestimated binding energies. 

PMID- 23557540
TI  - Use of micronutrient supplements among pregnant women in Alberta: results from
      the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.
AB  - Maternal nutrient intake in the prenatal period is an important determinant of
      fetal growth and development and supports maternal health. Many women, however,
      fail to meet their prenatal nutrient requirements through diet alone and are
      therefore advised to consume nutrient supplements. The purpose of this study was
      to describe the use of natural health products (NHP) by pregnant women in each
      trimester of pregnancy. Women (n = 599) participating in the first cohort of the
      Alberta Pregnancy Outcomes and Nutrition (APrON) study completed an interviewer
      administered supplement intake questionnaire during each trimester of pregnancy.
      NHP use was high, with >90% taking multivitamin/mineral supplements, and nearly
      half taking at least one additional single-nutrient supplement. Compliance with
      supplementation guidelines was high for folic acid (>90%), vitamin D (~70%) and
      calcium (~80%), but low for iron (<30%) and for all four nutrients together
      (<=11%). On average, women met or exceeded the recommended dietary allowance for
      folic acid, vitamin D and iron from NHPs alone, with median daily intakes of 1000
      MUg, 400 IU and 27 mg, respectively. The median calcium intake was 250 mg d(-1) .
      Up to 26% of women exceeded the tolerable upper intake level for folic acid and
      up to 19% did so for iron at some point of their pregnancy. Findings highlight
      the need to consider both dietary and supplemental sources of micronutrients when
      assessing the nutrient intakes of pregnant women. 

PMID- 23557544
TI  - Dyslipidemia promotes the progression of chronic kidney disease.

PMID- 23557543
TI  - Patient and physician related factors of adherence to evidence based guidelines
      in diabetes mellitus type 2, cardiovascular disease and prevention: a cross
      sectional study.
AB  - BACKGROUND: Patients do not always receive guideline-adherent therapy, yet little
      is known about the underlying causes on the patients' side. We quantified non
      guideline-adherent treatment of chronic diseases (diabetes mellitus,
      hypertension, cardiovascular disease, heart failure, atrial fibrillation) in
      primary care and analysed the causes from the physician's as well as the
      patient's view. METHODS: With the intention to analyze the frequency and causes
      of non-guideline-adherent treatment of patients with chronic diseases, we drew a
      random sample of 124 general practitioners (GP) in Salzburg, Austria, of which 58
      (46.8%) participated. In the participating GP surgeries, we consecutively
      recruited 501 patients with at least one of the target-diseases and checked the
      guideline conformity of treatment using 9 quality indicators. We then interviewed
      the patients as well as the general practitioners regarding factors affecting
      deviation from guideline recommendations. RESULTS: Of the 501 patients, a total
      of 1224 quality indicators could be analysed. Non-adherence to guideline
      recommendations were present in 16.8% (n = 205, 95% CI 14.7 to 18.8%) of all
      quality indicators. In 61.5% of these cases (n = 126, 95% CI 53.0 to 70.0%) the
      treatment was wrongly judged as not recommended by the physicians. In 10.2% (n =
      21, 95% CI 0 to 23.2%) physicians attributed non-adherence to patient's non
      compliance, and in 10.7% (n = 22, 95% CI 0 to 23.7%) to an adverse drug event,
      whereas only 5.4% (n = 11, 95% CI 0 to 18.7%) of non-adherence was related to an
      adverse drug event reported by the patients. Patients were unaware regarding the
      reason for non-adherent therapy in 64.4% (n = 132, 95% CI 56.2 to 72.6%) of the
      quality indicators. In 20.0% (n = 41, 95% CI 7.8 to 32.2%) patients regarded a
      drug as not needed. CONCLUSIONS: Guideline adherence in chronic care was
      relatively good in our study sample, but still leaving room for improvement.
      Physicians' lack of knowledge and patients' lack of awareness account for about
      70% of non-adherence, indicating the necessity to improve physician education,
      and patient involvement. In about 30% of the quality indicators not fulfilled,
      non-adherence is due to other reasons like adverse drug events or patients not
      willing to take a recommended drug.

PMID- 23557542
TI  - Real-world outcomes with recombinant factor VIIa treatment of acute bleeds in
      haemophilia patients with inhibitors: results from the international ONE
      registry.
AB  - The ONE Registry (OR) was an international prospective observational study of on
      demand recombinant factor VIIa (rFVIIa) treatment for mild to moderate bleeds in
      haemophilia A/B patients with inhibitors. To describe real-world use of single
      and multi dose rFVIIa and to compare outcomes, including effectiveness, safety,
      quality of life and treatment satisfaction associated with treatment. Baseline
      data included demographics, treatment, medical and bleed history and
      patient/caregiver-reported outcomes regarding bleeds. rFVIIa was prescribed
      according to routine practice; regimens varied and initial dose was categorized
      as low (LD, <= 120 MUg kg(-1) ), intermediate (ID, >120 and <250 MUg kg(-1) ) or
      high (HD, >= 250 MUg kg(-1) ). OR included 102 patients and 85 (83%) reported 494
      bleeds overall. Mean age was 23 years (SD 16.4), with 52% >= 18 years. Majority
      of bleeds (n = 350, 71%) involved >= 1 joints; 46% involved a target joint.
      Median initial dose was 90 MUg kg(-1) in LD (range 87-120, n = 156), 174 MUg kg(
      1) in ID, (range 121-249, n = 127) and 270 MUg kg(-1) in HD, (range 250-375, n =
      211). For spontaneous bleeds, effective haemostasis rate at 9 h was 63% LD, 60%
      ID and 56% HD. Rates of combined partially effective/effective haemostasis was
      85% LD, 96% ID and 86% HD. Median number of doses in HD was one (range 1-7),
      compared with two in LD (range 1-17) and ID (range 1-23). No thromboembolic
      events were reported in 1145 doses given. These observational data in real life
      are consistent with previous studies which have shown similar overall
      effectiveness of rFVIIa and similar effectiveness and safety across different
      patterns of standard initial dosing.

PMID- 23557545
TI  - Association between dyslipidemia and chronic kidney disease: a cross-sectional
      study in the middle-aged and elderly Chinese population.
AB  - BACKGROUND: Dyslipidemia, a well-known risk factor for cardiovascular disease, is
      common in patients with kidney disease. Recent studies discerned that
      dyslipidemias play a critical role in renal damage progression in renal diseases,
      but the association between dyslipidemias and chronic kidney disease (CKD) in the
      general population remains unknown. Thus, we assessed whether the growing
      prevalence of dyslipidemia could increase the risk of CKD. METHODS: A total of
      4779 middle-aged and elderly participants participated in this study.
      Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD
      was defined as albuminuria and/or reduced estimated glomerular filtration rate
      (eGFR, < 60 ml*min(-1)*1.73 m(-2)). Regression analysis was used to evaluate the
      association between dyslipidemia and albuminuria/reduced eGFR. RESULTS:
      Participants with hypercholesterolemia exhibited a greater prevalence of
      albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P =
      0.028, respectively). Both hypercholesterolemia and low high density lipoprotein
      cholesterol (HDL-C) were independently associated with albuminuria (odds ratio
      (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 -
      2.09, respectively). The multivariable adjusted OR of reduced eGFR in
      participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the
      number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI
      0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for
      albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85
      (95%CI 2.36 - 14.51) for reduced eGFR, respectively. CONCLUSIONS: Our findings
      indicate that dyslipidemias increase the risk of CKD in the middle-aged and
      elderly Chinese population. Hypercholesterolemia plays an important role in
      reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with
      an increased risk for albuminuria.

PMID- 23557546
TI  - Prevalence of chronic kidney disease and prediabetes and associated risk factors:
      a community-based screening in Zhuhai, Southern China.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) and prediabetes has
      increased in China, and at different rates in different locations. Therefore a
      community-based screening research was conducted in order to determine the
      prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD
      and prediabetes in a city of Southern China. METHODS: A total of 7801 community
      residents aged 18 year and older from 6 communities were screened by a stratified
      random cluster sampling method. An estimated glomerular filtration rate (eGFR),
      albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of
      insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was
      calculated by the direct method with the use of data on the population
      distribution in China in 2006. Multivariate logistic analysis was used to analyze
      the risk factors of CKD and prediabetes, and association of insulin resistance
      (IR) with CKD and prediabetes was analyzed. RESULTS: The age-standardized
      prevalence of CKD was 12.5%, eGFR < 60 ml*min(-1)*1.73 m(-2) was 2.7% and ACR
      (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized
      prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a
      common independent risk factor of CKD and prediabetes. Further analysis show that
      HOMA-IR was increased with the aggravation of kidney injury and FPG. CONCLUSION:
      CKD and prediabetes have become a major public health problem in Zhuhai, Southern
      China; insulin resistance may be an important risk factor.

PMID- 23557547
TI  - Virtual reality simulator for training urologists on transurethral prostatectomy.
AB  - BACKGROUND: A virtual reality simulator provides a novel training model for
      improving surgical skills in a variety of fields. They can simulate a variety of
      surgical scenarios to improve the overall skills required for endoscopic
      operations, and also record the operative process of trainees in real-time and
      allow for objective evaluation. At present, some simulators for transurethral
      resection of the prostate (TURP) are available. The utility of virtual reality
      simulators in training of transurethral prostatectomy was investigated. METHODS:
      Thirty-eight urologists were randomly selected to take part in a simulation based
      training of TURP using the TURPSim(TM) system. Pre and post-training global rate
      scale (GRS) scores and objective parameters recorded by the simulator were
      assessed. Then, questionnaires were filled out. RESULTS: Compared with baseline
      levels, the GRS scores of trainees increased (18.0 +/- 4.0 vs. 12.4 +/- 4.2, P <
      0.001), while the rate of capsule resection (26.3% +/- 0.6% vs. 21.2% +/- 0.4%, P
      < 0.001), amount of blood loss ((125.8 +/- 86.3) ml vs. (83.7 +/- 41.6) ml, P <
      0.001), external sphincter injury (3.6 +/- 2.9 vs. 2.0 +/- 2.0, P < 0.001)
      decreased significantly after training. Most trainees were satisfied with the
      simulator based training and believed that the simulator accurately mimicked
      actual surgical procedures and could help improve their surgical skills.
      CONCLUSIONS: As a new method of training on transurethral prostatectomy skills,
      training of TURP using a virtual simulator can help urologists improve their
      surgical skills and safety. Therefore, the application of the TURPSim(TM) system
      in education and training of urologic surgery is warranted.

PMID- 23557548
TI  - Mycophenolate mofetil affects monocyte Toll-like receptor 4 signaling during
      mouse renal ischemia/reperfusion injury.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) has been used to prevent transplant
      rejection for many years and has been shown to have protective effects against
      renal failure. The objective was to investigate the effect of MMF on monocyte
      Toll-like receptor 4 (TLR4) signaling in the early stages of renal
      ischemia/reperfusion injury (IRI) of mice. METHODS: Sixty BALB/C mice were
      randomly divided into two groups: an IRI group, in which renal IRI was induced by
      clamping the renal pedicles for 45 minutes, and an MMF group, in which MMF was
      given (40 mg*kg(-1)*d(-1), intraperitoneally) from 2 days before renal IRI. The
      plasma creatinine level and renal tissue damage of each group mice were observed
      6, 12, 24, and 48 hours after reperfusion. The concentration of plasma high
      mobility group box 1 (HMGB-1) (TLR4 ligand), interleukin 6 (IL-6), monocyte
      chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-alpha)
      and the expression of TLR-4 on monocytes were determined. RESULTS: The plasma
      creatinine concentration in the MMF group was lower compared to the IRI group
      (after reperfusion of 6, 12, 24, or 48 hours, P < 0.05). Pathological analysis
      showed that the renal damage was slighter, TLR-4 expression was reduced (after
      reperfusion of 6, 12, 24, or 48 hours, P < 0.05), and the concentration of
      cytokines in the plasma was lower (P < 0.05) in the MMF group. No differences in
      the concentrations of HMGB-1 were observed (P > 0.05). CONCLUSION: Monocyte TLR4
      signaling is important in the early stage of kidney IRI, but MMF can inhibit it
      and improve renal function.

PMID- 23557549
TI  - Acortatarin A inhibits high glucose-induced extracellular matrix production in
      mesangial cells.
AB  - BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal
      disease. Various treatment regimens and combinations of therapies provide only
      partial renoprotection. Therefore new approaches are needed to retard the
      progression of DN. The aim of the present study was to evaluate the role of a
      novel spiroalkaloid from Acorus tatarinowii named acortatarin A (AcorA) in
      inhibiting high glucose-induced extracellular matrix accumulation in mesangial
      cells (MCs). METHODS: The cytotoxity of AcorA on MCs was examined by 3-(4,5
      dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. The expression
      of fibronectin and collagen IV was examined by real time PCR and western
      blotting. The expression of p22(phox) and p47(phox) was detected by western blot.
      The interaction between p22(phox) and p47(phox) was examined by co
      immunoprecipitation. The phosphorylation of p47(phox) was examined by
      immunoprecipitation. The phosphorylation of protein kinase C (PKC) alpha,
      PKCbeta, phospholiase C gamma (PLCgamma1), and the p85 subunit of PI3K was
      determined by Western blotting. RESULTS: AcorA significantly inhibited high
      glucose-induced activation of NADPH oxidase, a ROS-generating enzyme, by
      increasing phosphorylation of p47(phox) and enhancing interaction between
      p22(phox) and p47(phox). Preincubation of AcorA with MCs inhibited high glucose
      induced collagen IV and fibronectin production in a dose-dependent manner.
      Moreover, AcorA attenuated high glucose enhanced phosphorylation of PKCalpha,
      PKCbeta, PLCgamma1, and the p85 subunit of PI3K. CONCLUSION: AcorA inhibits high
      glucose-induced extracellular matrix production via blocking NADPH oxidase
      activation.

PMID- 23557550
TI  - In-hospital medical complications associated with patient dependency after acute
      ischemic stroke: data from the China National Stroke Registry.
AB  - BACKGROUND: The mortality of stroke patients is strongly affected by medical
      complications. However, there are limited data investigating the effect of in
      hospital medical complications on the dependency of stroke patients worldwide. We
      prospectively and systematically investigated the effect of medical complications
      on dependency of patients at 3, 6 and 12 months after stroke using the China
      National Stroke Registry (CNSR). METHODS: This prospective cohort study collected
      data of patients age > 18 years with acute ischemic stroke in 132 clinical
      centers distributed across 32 provinces and four municipalities (including Hong
      Kong region) of China, from September 2007 to August 2008. Data on medical
      complications, dependency and other information were obtained from paper-based
      registry forms. Medical complications associated with stroke outcomes were
      assessed using multivariable Logistic regression. RESULTS: Of 11 560 patients
      with acute ischemic stroke, 1826 (15.80%) presented with in-hospital medical
      complications. In-hospital medical complications were independent risk factors
      for dependency of patients at 3 months (adjusted odds ratio (OR) 2.367, 95%
      confidence interval (CI) 2.021 - 2.771), 6 months (adjusted OR 2.257, 95%CI 1.922
      - 2.650), and 12 months (adjusted OR 1.820, 95%CI 1.538 - 2.154) after acute
      ischemic stroke. CONCLUSION: The results demonstrated that the short-term and
      long-term dependency of acute ischemic stroke patients is significantly
      associated with in-hospital medical complications in China.

PMID- 23557551
TI  - Effect of aliskiren on arterial stiffness, compared with ramipril in patients
      with mild to moderate essential hypertension.
AB  - BACKGROUND: Aliskiren is a novel blood pressure-lowering agent acting as an oral
      direct renin inhibitor. The aim of this study was to assess the effect of
      aliskiren on arterial stiffness, compared with that of ramipril in mild to
      moderate essential hypertensive patients. METHODS: Following a two week placebo
      run-in period, patients with a mean sitting diastolic blood pressure (ms-DBP) >=
      95 and < 110 mmHg (1 mmHg = 0.133 kPa), and a mean sitting systolic blood
      pressure (ms-SBP) < 180 mmHg were randomly allocated to treatment with aliskiren
      (150 mg/d, n = 20) or ramipril (5 mg/d, n = 20) for eight weeks. Blood pressure,
      plasma renin activity, and the brachial-ankle pulse wave velocity (ba-PWV) were
      measured before and after eight weeks of treatment. RESULTS: Eight weeks of
      treatment significantly decreased systolic blood pressure and diastolic blood
      pressure in both the aliskiren group and ramipril group. The hypotensive effect
      did not differ between the two groups. Plasma renin activity decreased after
      aliskiren treatment and increased after ramipril treatment. There was no
      significant difference in baseline ba-PWV between the aliskiren and ramipril
      groups (P = 0.892). The ba-PWV was significantly reduced in both the aliskiren
      group (1535 (1405 - 1666) vs. 1464 (1360 - 1506) cm/s) (P < 0.01) and the
      ramipril group (1544 (1433 - 1673) vs. 1447 (1327 - 1549) cm/s) (P < 0.01). No
      statistically significant difference was found in the decline of ba-PWV between
      the two groups (P = 0.766). CONCLUSIONS: The current study revealed that
      aliskiren (150 mg/d) could ameliorate arterial stiffness and its effect was
      similar to ramipril (5 mg/d) in mild to moderate hypertensive patients,
      indicating that in addition to lowering blood pressure, aliskiren had beneficial
      effect on vascular protection.

PMID- 23557552
TI  - A complex urinary fistula after Bricker ileal conduit.

PMID- 23557553
TI  - Coronary bifurcation lesions treated with double kissing crush technique compared
      to classical crush technique: serial intravascular ultrasound analysis.
AB  - BACKGROUND: The double kissing (DK) crush technique is a modified version of the
      crush technique. It is specifically designed to increase the success rate of the
      final kissing balloon post-dilatation, but its efficacy and safety remain
      unclear. METHODS: Data were obtained from the DKCRUSH-I trial, a prospective,
      randomized, multi-center study to evaluate safety and efficacy. Post-procedural
      and eight-month follow-up intravascular ultrasound (IVUS) analysis was available
      in 61 cases. Volumetric analysis using Simpson's method within the Taxus stent,
      and cross-sectional analysis at the five sites of the main vessel (MV) and three
      sites of the side branch (SB) were performed. Impact of the bifurcation angle on
      stent expansion at the carina was also evaluated. RESULTS: Stent expansion in the
      SB ostium was significantly less in the classical crush group ((53.81 +/-
      13.51)%) than in the DK crush group ((72.27 +/- 11.46)%) (P = 0.04). For the MV,
      the incidence of incomplete crush was 41.9% in the DK group and 70.0% in the
      classical group (P = 0.03). The percentage of neointimal area at the ostium had a
      tendency to be smaller in the DK group compared with the classical group ((16.4
      +/- 19.2)% vs. (22.8 +/- 27.1)%, P = 0.06). The optimal threshold of post
      procedural minimum stent area (MSA) to predict follow-up minimum lumen area (MLA)
      < 4.0 mm(2) at the SB ostium was 4.55 mm(2), yielding an area under the curve of
      0.80 (95% confidence interval: 0.61 to 0.92). CONCLUSION: Our data suggest that
      the DK crush technique is associated with improved quality of the final kissing
      balloon inflation (FKBI) and had smaller optimal cutoff value of post-procedural
      MSA at the SB ostium.

PMID- 23557554
TI  - Relationship between linguistic functions and cognitive functions in a clinical
      study of Chinese patients with post-stroke aphasia.
AB  - BACKGROUND: There has been a long debate among scholars surrounding the
      relationship between language and cognition. The worldwide study of aphasia is
      actively exploring the function of language from cognitive point of view. This
      study aimed to investigate the relationship between linguistic functions and
      cognitive functions in a clinical study of Chinese patients with post-stroke
      aphasia. METHODS: Cognitive functions of 63 Chinese patients with aphasia
      following a stroke were assessed with the Chinese version of the second edition
      of Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) battery and
      their linguistic functions were tested with the Western Aphasia Battery (WAB)
      Scale, respectively. The correlation between the results observed on the LOTCA
      battery and those on the WAB was analyzed. Aphasia quotient, performance
      quotient, cortical quotient, and linguistic function of the patients were
      compared. Then, each language function was analyzed by way of dependent adopt
      multiple regression analysis. RESULTS: The total score of 63 patients as shown on
      the LOTCA battery was significantly correlated with the aphasia quotient,
      performance quotient, and cortical quotient observed on the WAB Scale (P < 0.05,
      P < 0.01). However, the correlation between visuomotor organization under LOTCA
      and repeat under WAB was not significant (P > 0.05). The attention of LOTCA and
      WAB's spontaneous speech, repeat, naming, and aphasia quotient was not relevant
      either (P > 0.05). In addition, correlations between the results observed on the
      LOTCA battery and the WAB were significant (P < 0.05, P < 0.01). Among the
      significant variables finally entered into the standardized canonical
      discriminant functions, main factors affected the aphasia. Multiple regression
      analysis showed that orientation, spatial perception, and visual perception had a
      notable influence on aphasia quotient and naming. Orientation and thinking
      operation was found to have a notable influence on spontaneous speech. Spatial
      perception and visual perception was found to have a notable influence on
      auditory comprehension. Thinking operation and orientation was found to have an
      obvious influence on reading. Thinking operation, spatial perception, and
      attention was found to have a notable effect on writing (P < 0.01). CONCLUSION:
      There exists a close relationship between linguistic functions and cognitive
      orientation, spatial perception, visual perception, and thinking operation in a
      clinical study of Chinese patients with post-stroke aphasia.

PMID- 23557555
TI  - Impact of HIV/sexually transmitted infection testing on risky sexual behaviors
      among men who have sex with men in Langfang, China.
AB  - BACKGROUND: Men who have sex with men (MSM) in China remain at high risk for HIV
      infection, the proportion of reported HIV/AIDS cases that occurred among MSM rose
      greatly from 2005 to 2011. HIV testing and counseling is a critical HIV
      prevention strategy among HIV related high-risk population, including MSM in
      China. This article aimed to assess the association between receiving HIV testing
      and high-risk sexual behaviors among MSM in Langfang, Hebei Province, China.
      METHODS: Between September and November 2007, 233 MSM were recruited to receive
      an HIV testing intervention. Face-to-face interviews were conducted before HIV
      testing and 3 months later HIV-related risk behaviors were assessed. Serological
      testing for HIV and other sexually transmitted infections (STIs) was performed.
      RESULTS: Of the recruited 233 MSM, 200 completed follow-up. Baseline prevalence
      was 7.8% for HIV, 21.0% for syphilis, 15.8% for gonorrhea, and 5.0% for
      chlamydia. Multivariate analysis indicated that inconsistent condom use (OR =
      7.9, 95%CI: 0.9 - 66.7, P = 0.059) and bleeding during anal sex (OR = 5.9, 95%CI:
      1.3 - 26.2, P = 0.019) were risk factors for HIV infection, and group sex (OR =
      6.6, 95%CI: 2.2 - 19.7, P = 0.001) was a risk factor for syphilis infection at
      baseline. At 3 months follow-up, among STI-positive MSM, self-reported anal sex
      fell from 73.1% to 38.5% (P < 0.001); group sex fell from 19.2% to 5.8% (P <
      0.001); and bleeding during anal sex fell from 23.1% to 5.8% (P < 0.001). Among
      STI-negative MSM, the frequency of one-night stands fell from 32.5% to 17.2% (P <
      0.001), and oral sex rose from 57% to 78.5% (P < 0.001). STI-positive MSM were
      less likely to engage in anal sex compared to STI-negative MSM (chi(2) = 5.189, P
      = 0.023). CONCLUSIONS: HIV testing is an important intervention strategy among
      MSM. HIV testing services among MSM need to be scaled up, along with
      comprehensive, tailored interventions including condom promotion and STI
      treatment.

PMID- 23557556
TI  - A novel pressure difference-induced perforation aortic stent-grafts system: an
      experimental study.
AB  - BACKGROUND: Most of endovascular stent-graft modifications to preserve side
      branch must be customized according to extensive pre-operative assessment, which
      may not be possible in many hospitals and emergency settings. The study was to
      develop a novel stent-grafts system that would allow in situ "fenestration", with
      less reliance on preoperative imaging. METHODS: The magnitude of pressure
      difference (PD) between left subclavian artery (LSA) and aortic arch were
      measured in 12 experimental pigs. Changes of PD before and after LSA was covered
      were analyzed respectively. The novel stent graft was made by multi-dimensional
      and multiple textiles forming technology. According to the PD measurement in
      pigs, we evaluated the feasibility of the stent-graft in a mock circulation
      system. RESULTS: In pigs, the blood pressure of aortic arch was significantly
      higher than that of LSA after it was covered (P < 0.001) and PD was (42.78 +/-
      5.17) mmHg. After target vessel was covered and when PD between the LSA and aorta
      reached the magnitude measured in pigs, contrast media oozed from the cranny of
      graft to the LSA, which was generated by sliding and deformation of yarns of
      novel stent-graft. CONCLUSIONS: The study proposes the design of pressure
      difference-induced perforation aortic stent-grafts system and verifies that the
      PD between LSA and aortic arch is high enough to allow in situ "fenestration" by
      stent graft made by multi-dimensional and multiple textiles forming technology.

PMID- 23557557
TI  - High risk factors of brain metastases in 295 patients with advanced breast
      cancer.
AB  - BACKGROUND: The incidence of brain metastases in patients with breast cancer is
      approximately 10% - 16%, and survival after diagnosis of brain metastases is
      usually short. This study was designed to evaluate the risk factors associated
      with brain metastases in advanced breast cancer patients, with a view to help
      predict patient groups with high risk of brain metastases. METHODS: In total, 295
      patients with advanced breast cancer were evaluated. All patients were
      pathologically confirmed and metastatic lesions were confirmed pathologically or
      by imaging. All patients were examined at least once every 6 months with head CT
      or MRI. Patients showing symptoms underwent immediate inspection, and brain
      metastatic lesions were confirmed by head CT and/or MRI. RESULTS: At a median
      follow-up of 12 months from the occurrence of metastases, brain metastases had
      occurred in 49 patients (16.6%). In our univariate analysis, variables
      significantly related to increased risk of brain metastases were hormone receptor
      negative tumors, epidermal growth factor receptor 2 (HER2)-positive tumors, and
      multiple distant metastases. Patients with dominant tumor sites in soft tissue,
      or defined as Luminal A subtype, tended to have a lower risk of brain metastases
      than patients with visceral metastases, Luminal B subtype, triple-negative
      subtype or HER2-enriched subtype tumors. CONCLUSIONS: Our results strongly
      suggest that factors such as Luminal B, triple-negative, and HER2-enriched
      subtypes are high risk factors for brain metastases. These data, therefore,
      provide pivotal clinical evidence towards a comprehensive understanding of the
      risk factors of brain metastases in advanced breast cancer patients.

PMID- 23557558
TI  - Intranasal endoscopic prelacrimal recess approach to maxillary sinus.
AB  - BACKGROUND: The inferior turbinate (IT) and nasolacrimal duct (NLD) are often
      sacrificed while managing the diffuse lesion of maxillary sinus (MS). We report a
      new approach to MS without ablation of NLD and IT. METHODS: This retrospective
      study enrolled 19 hospitalized patients (aged from 42 to 68 years) who underwent
      endoscopic sinus surgery between 2003 and 2008. Twelve patients had inverted
      papilloma (IP), two had nasal polyps, two had Kubo's postoperative cyst of MS,
      one had recurrent bone cyst of maxilla, one had dentigerous cyst and one had
      bleeding of internal maxillary artery secondary to Caldwell-Luc operation
      respectively. Two IP patients were excluded from this group since the follow-up
      time was less than 12 months. The NLD was dissected after removing the anterior
      bony portion of nasal lateral wall. The prelacrimal recess approach (PLRA) to MS
      was established when IT-NLD flap was raised medially. The flap was repositioned
      when MS lesion was removed. RESULTS: All the 17 patients had unilateral lesions.
      Ten MS IP patients were at the T3 Krouse stage. The follow-up ranged from 7 to 60
      months. No recurrence was seen in 16 patients. Only one IP patient had a local
      recurrence in MS. All of them had no any complications. CONCLUSION: The diffuse
      or severe diseases of MS may be the potential indications for PLRA.

PMID- 23557559
TI  - Clinicopathology, immunophenotype, T cell receptor gene rearrangement, Epstein
      Barr virus status and p53 gene mutation of cutaneous extranodal NK/T-cell
      lymphoma, nasal-type.
AB  - BACKGROUND: Extranodal natural killer/T-cell (NK/T cell) lymphoma, nasal-type, is
      a rare lymphoma. Skin is the second most common site of involvement after the
      nasal cavity/nasalpharynx. The aim of this study was to investigate the
      clinicopathologic features, immunophenotype, T cell receptor (TCR) gene
      rearrangement, the association with Epstein-Barr virus (EBV) infection and p53
      gene mutations of the lymphoma. METHODS: The clinicopathologic analysis,
      immunohistochemistry, in situ hybridization for EBER1/2, TCR gene rearrangement
      by polymerase chain reaction (PCR), mutations of p53 gene analyzed by PCR and
      sequence analysis were employed in this study. RESULTS: In the 19 cases, the
      tumor primarily involved the dermis and subcutaneous layer. Immunohistochemical
      staining showed that most of the cases expressed CD45RO, CD56, CD3epsilon, TIA-1
      and GrB. Three cases were positive for CD3 and two cases were positive for CD30.
      Monoclonal TCRgamma gene rearrangement was found in 7 of 18 cases. The positive
      rate of EBER1/2 was 100%. No p53 gene mutation was detected on the exon 4 - 9 in
      the 18 cases. Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide
      polymorphisms (SNPs) on the exon 4 at codon 72. The expression of p53 protein was
      72% (13/18) immunohistochemically. CONCLUSIONS: Cutaneous NK/T-cell lymphoma is a
      rare but highly aggressive lymphoma with poor prognosis. No p53 gene mutation was
      detected on the exon 4 - 9, and Pro/Arg SNPs on p53 codon 72 were detected in the
      cutaneous NK/T-cell lymphoma. The overexpression of p53 protein may not be the
      result of p53 gene mutation.

PMID- 23557560
TI  - Application of computer-assisted three-dimensional quantitative assessment and a
      surgical planning tool for living donor liver transplantation.
AB  - BACKGROUND: Precise evaluation of the live donor's liver is the most important
      factor for the donor's safety and the recipient's prognosis in living donor liver
      transplantation (LDLT). Our study assessed the clinical value of computer
      assisted three-dimensional quantitative assessment and a surgical planning tool
      for donor evaluation in LDLT. METHODS: Computer-assisted three-dimensional (3D)
      quantitative assessment was used to prospectively provide quantitative assessment
      of the graft volume for 123 consecutive donors of LDLT and its accuracy and
      efficiency were compared with that of the standard manual-traced method. A case
      of reduced monosegmental LDLT was also assessed and a surgical planning tool
      displayed the precise surgical plan to avoid large-for-size syndrome. RESULTS:
      There was no statistically significant difference between the detected graft
      volumes with computer-assisted 3D quantitative assessment and manual-traced
      approaches ((856.76 +/- 162.18) cm(3) vs. (870.64 +/- 172.54) cm(3), P = 0.796).
      Estimated volumes by either method had good correlation with the actual graft
      weight (r-manual-traced method: 0.921, r-3D quantitative assessment method:
      0.896, both P < 0.001). However, the computer-assisted 3D quantitative assessment
      approach was significantly more efficient taking half the time of the manual
      traced method ((16.91 +/- 1.375) minutes vs. (39.27 +/- 2.102) minutes, P < 0.01)
      to estimate graft volume. We performed the reduced monosegmental LDLT, a
      pediatric case, with the surgical planning tool (188 g graft in the operation,
      which was estimated at 208 cm(3) pre-operation). The recipient recovered without
      large-for-size syndrome. CONCLUSIONS: Computer-assisted 3D quantitative
      assessment provided precise evaluation of the graft volume. It also assisted
      surgeons with a better understanding of the hepatic 3D anatomy and was useful for
      the individual surgical planning tool.

PMID- 23557561
TI  - Axonal loss and blood flow disturbances in the natural course of indirect
      traumatic optic neuropathy.
AB  - BACKGROUND: Indirect traumatic optic neuropathy (TON) is an acute injury of the
      optic nerve associated with severe visual dysfunction, which may be a result of
      secondary mechanical injury and vascular disorder of the optic nerve due to
      trauma. We analyzed the natural course of axonal loss and blood flow disturbances
      in patients with indirect TON to find a possible therapeutic window. METHODS: A
      cohort of 54 patients with indirect TON recruited between October 2008 and
      October 2010 at Beijing Tongren Hospital was retrospectively analyzed. The
      patients were divided into no light perception group (NLP) and better than NLP
      (btNLP) group. Specifically, the thickness of the retinal nerve fiber layer
      (RNFL) measured by spectral domain optical coherence tomography (SD-OCT), and
      hemodynamic parameters of the ophthalmic artery (OA), central retinal artery
      (CRA) and posterior ciliary artery (PCA) were determined. RESULTS: Two weeks
      after injury, there was a statistically significant decrease in the thickness of
      RNFL in the btNLP group as compared with the fellow control eyes (P < 0.05). In
      contrast, in the NLP group, RNFL thickness slightly increased for 2 weeks
      following injury, then overtly reduced after 4 weeks (P < 0.05). Peak systolic
      velocity (PSV) of CRA was significantly decreased 4 weeks after injury (P < 0.05)
      in both the NLP group and btNLP group (P < 0.05). The thickness of RNFL in the
      NLP group was negatively correlated with PSV of CRA after 1 week of injury (P <
      0.05, r = -0.962). CONCLUSIONS: SD-OCT is a useful supplement in detecting the
      axonal loss in TON. The dynamic change of the thickness of RNFL appears to
      correlate with the hemodynamic disturbances in the natural course of TON. The
      first 2 weeks following an injury is critical and should be considered as the
      therapeutic window for TON patients.

PMID- 23557562
TI  - Cochlear implantation effect on deaf children with gap junction protein beta 2
      gene mutation.
AB  - BACKGROUND: The popularization and promotion of gene diagnosis technology makes
      it possible to detect deafness genes for children with congenital hearing
      impairment, and the proportion of gap junction protein beta 2 (GJB2) gene
      mutations in cochlear implant patients is 26.5%. We did follow-up evaluation on
      auditory rehabilitation effect for all 31 deaf children with GJB2 gene mutation
      after cochlear implantation to provide a reference for such patients. METHODS:
      Application of "the genetic deafness gene chip detection kit" and "gene complete
      sequence analysis" were applied to conduct detection on common genetic deafness
      gene mutation hotspots of the hearing impaired children with cochlear
      implantation. To conduct auditory rehabilitation effect evaluation on all 31
      cases of patients with GJB2 genetic deafness after 3, 6 and 12 months of the
      operation respectively. The single factor repeated measure analysis of variance
      (ANOVA) was applied to analysis whether there were significant difference among
      the results of initial consonant of a Chinese syllable recognition at 3 different
      stages after the operation, the results of vowel of a Chinese syllable
      recognition at 3 different stages after the operation, and the results of two
      syllable recognition at 3 different stages after the operation. RESULTS: The
      235delC is the high-incidence mutational site in 31 cases of patients with GJB2
      genetic deafness, and the total detection rate is up to 90.3% (28/31). There were
      significant differences in the initial consonant and the vowel of a Chinese
      syllable recognition rate, and the two-syllable recognition rates at 3, 6, and 12
      months after the operation (P < 0.01). CONCLUSION: Cochlear implantation is a
      safe and effective measure for auditory reconstruction, enabling patients with
      GJB2 hereditary severe sensorineural deafness to achieve auditory speech
      recognition effectively.

PMID- 23557563
TI  - Transplantation of neural stem cells overexpressing glial cell line-derived
      neurotrophic factor enhances Akt and Erk1/2 signaling and neurogenesis in rats
      after stroke.
AB  - BACKGROUND: Our previous studies have indicated that the beneficial effects of
      grafting neural stem cells (NSCs) overexpressing glial cell line-derived
      neurotrophic factor (GDNF) in rats after stroke. However, the underlying
      mechanisms are highly debatable. In this study, we investigated whether
      neurogenesis, Akt, and extracellular signal-regulated kinase 1/2 (Erk1/2)
      signaling were involved in this process. METHODS: Transient ischemic stroke were
      induced by occluding middle cerebral artery for 2 hours and reperfusion. At 3
      days after reperfusion, GDNF/NSCs, NSCs, and vehicle were administered.
      Immunohistochemical staining was used to evaluate neurogenesis by nestin
      antibody; phosphorylation of Akt and Erk1/2 was investigated by Western blotting
      analysis. RESULTS: Transplantation of GDNF/NSCs and NSCs significantly increased
      nestin-positive cells compared to control group (vehicle) from 1 to 7 weeks after
      reperfusion, and GDNF/NSCs showed stronger effect than NSCs at 2 and 3 weeks
      after reperfusion. Meanwhile, enhanced phosphorylation level of Erk1/2 was
      observed in the GDNF/NSCs and NSCs groups compared with control group, and
      phosphorylation level of Erk1/2 in GDNF/NSCs group was remarkably higher than
      that of NSCs group at any given time. In contrast, expression of mitogen
      activated protein kinase phosphatase-1 (MKP-1), known as inhibitor of Erk1/2
      signaling, was significantly decreased in the GDNF/NSCs and NSCs groups compared
      with the control group. Moreover, much enhanced and prolonged phosphorylation
      level of Akt of GDNF/NSCs group was detected compared with control and NSCs
      group. CONCLUSION: Grafting GDNF/NSCs enhances neurogenesis and activates Akt and
      Erk1/2 signaling, that may provide the potential for GDNF/NSCs in stroke
      treatment.

PMID- 23557564
TI  - Design and preparation of polyurethane-collagen/heparin-conjugated
      polycaprolactone double-layer bionic small-diameter vascular graft and its
      preliminary animal tests.
AB  - BACKGROUND: People recently realized that it is important for artificial vascular
      biodegradable graft to bionically mimic the functions of the native vessel. In
      order to overcome the high risk of thrombosis and keep the patency in the
      clinical small-diameter vascular graft (SDVG) transplantation, a double-layer
      bionic scaffold, which can offer anticoagulation and mechanical strength
      simultaneously, was designed and fabricated via electrospinning technique.
      METHODS: Heparin-conjugated polycaprolactone (hPCL) and polyurethane (PU)
      collagen type I composite was used as the inner and outer layers, respectively.
      The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility
      was demonstrated by the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium
      bromide (MTT) test in vitro and subcutaneous implants in vivo respectively. The
      grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral
      artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to
      investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post
      transplantation. After angiography, the patent grafts were explanted for
      histological analysis. RESULTS: The double-layer bionic SDVG meet the clinical
      mechanical demand. Its good biocompatibility was proven by cytotoxicity
      experiment (the cell's relative growth rates (RGR) of PU-collagen outer layer
      were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%,
      100.0% and 98.0%, on days 1, 3, and 5, respectively) and the subdermal implants
      experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs
      were patent without any aneurismal dilatation or obvious anastomotic stenosis at
      the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at
      the 2nd week. Histological analysis and SEM showed that the inner layer was
      covered by new endothelial-like cells. CONCLUSION: The double-layer bionic SDVG
      is a promising candidate as a replacement of native small-diameter vascular
      graft.

PMID- 23557565
TI  - Hypertonic saline resuscitation contributes to early accumulation of circulating
      myeloid-derived suppressor cells in a rat model of hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock is usually associated with complicated immune and
      inflammatory responses, which are sometimes crucial for the prognosis. As
      regulators of the immune and inflammatory system; proliferation, migration,
      distribution and activation of myeloid-derived suppressor cells (MDSCs) are
      intimately linked to the inflammation cascade. METHODS: In a model of severe
      hemorrhagic shock, thirty-five rats were randomly divided into control, sham,
      normal saline resuscitation (NS), hypertonic saline resuscitation (HTS), and
      hydroxyethyl starch resuscitation (HES), with seven in each group. MDSCs were
      analyzed by flow cytometric staining of CD11b/c(+)Gra(+) in peripheral blood
      mononuclear cells (PBMC), spleen cell suspensions, and bone marrow nucleated
      cells (BMNC). Simultaneously, the expressions of arginase-1 (ARG-1) and inducible
      nitric oxide synthase (iNOS) mRNA in MDSCs were evaluated by quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR). RESULTS: In the early stage
      after hemorrhagic shock, fluid resuscitation and emergency treatment, the MDSCs
      in the PBMC of NS, HTS and HES groups markedly increased, and MDSCs in BMNC of
      these groups decreased accordingly, significantly different to the control group.
      In hemorrhagic shock rats infused with HTS at the early resuscitation stage,
      MDSCs in PBMC increased about 2 and 4 folds, and MDSCs in BMNC decreased about
      1.3 and 1.6 folds, as compared to the sham group respectively, with statistically
      significant difference. Furthermore, compared to the NS and HES groups, the MDSCs
      in PBMC of HTS group increased 1.6 and 1.8 folds with statistically significant
      differences; the MDSCs decrease in BMNC was not significant. However, there was
      no statistically significant difference in MDSCs of spleen among the five groups.
      In addition, compared to the control, sham, NS and HES groups, the ARG-1 and iNOS
      mRNA of MDSCs in PBMC, spleen and BMNC in the HTS group had the highest level of
      expression, but no statistically significant differences were noted. CONCLUSIONS:
      In this model of rat with severe and controlled hemorrhagic shock, small volume
      resuscitation with HTS contributes to dramatically early migration and
      redistribution of MDSCs from bone marrow to peripheral circulation, compared to
      resuscitation with NS or HES.

PMID- 23557566
TI  - A preliminary experimental study on the cardiac toxicity of glutamate and the
      role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor in
      rats.
AB  - BACKGROUND: Monosodium L-glutamate (MSG) is a food flavour enhancer and its
      potential harmfulness to the heart remains controversial. We investigated whether
      MSG could induce cardiac arrhythmias and apoptosis via the alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA) receptor. METHODS: Myocardial
      infarction (MI) was created by ligating the coronary artery and ventricular
      arrhythmias were monitored by electrocardiogram in the rat in vivo. Neonatal rat
      cardiomyocytes were isolated and cultured. Cell viability was estimated by 3
      (4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay. Calcium
      mobilization was monitored by confocal microscopy. Cardiomyocyte apoptosis was
      evaluated by acridine orange staining, flow cytometry, DNA laddering, reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting. RESULTS:
      MSG (i.v.) decreased the heart rate at 0.5 g/kg and serious bradycardia at 1.5
      g/kg, but could not induce ventricular tachyarrhythmias in normal rats in vivo.
      In rats with acute MI in vivo, however, MSG (1.5 g/kg, i.v.) induced ventricular
      tachyarrhythmias and these arrhythmias could be prevented by blocking the AMPA
      and N-methyl-d-aspartate (NMDA) receptors. Selectively activating the AMPA or
      NMDA receptor induced ventricular tachyarrhythmias in MI rats. At the cellular
      level, AMPA induced calcium mobilization, oxidative stress, mitochondrial
      dysfunction and apoptosis in cultured cardiomyocytes, especially when the AMPA
      receptor desensitization were blocked by cyclothiazide. The above toxic cellular
      effects of AMPA were abolished by AMPA receptor blockade or by H2O2 scavengers.
      CONCLUSIONS: MSG induces bradycardia in normal rats, but triggers lethal
      tachyarrhythmias in myocardial infarcted rats probably by hindering AMPA
      receptors. AMPA receptor overstimulation also induces cardiomyocyte apoptosis,
      which may facilitate arrhythmia.

PMID- 23557567
TI  - Biodistribution and preparation of technetium-99m-labeled D-D3 monoclonal
      antibody against pro-gastrin-releasing peptide (31-98) in mice.
AB  - BACKGROUND: We previously reported that iodine-131((131)I)-labeled anti-pro
      gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could
      selectively accumulate in the tumor sites of nude mice bearing small cell lung
      cancer (SCLC) xenografts. However, (131)I-D-D3 was cleared slowly from the body,
      and the best radioimmunoimaging time for SCLC was 72 - 96 hours after injection.
      The aims of this study were to radiolabel anti-ProGRP(31-98) D-D3 monoclonal
      antibody with technetium-99m ((99m)Tc) and to investigate the biodistribution of
      this antibody in healthy ICR mice. METHODS: D-D3 was labeled with (99m)Tc via the
      2-mercaptoethanol reduction method. (99m)Tc-D-D3 was purified by the gel column
      separation method. The labeling efficiency and radiochemical purity were measured
      by thin-layer chromatography. The immunological activity of (99m)Tc-D-D3 was
      determined with cell conjugation assays. (99m)Tc-D-D3 was injected into healthy
      ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by
      cervical dislocation at a designated time. Then, the blood and major organs were
      removed and weighed, and counted in a gamma scintillation counter to determine
      the percentage of the injected dose per gram (%ID/g). RESULTS: The labeling rate
      and the radiochemical purity of (99m)Tc-D-D3 were (73.87 +/- 2.89)% and (94.13 +/
      4.49)%, respectively. The immunobinding rates of (99m)Tc-D-D3 to the human small
      cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were
      (81.2 +/- 2.37)% and (24.3 +/- 1.46)%, respectively. The distribution data of
      normal ICR mice demonstrated that (99m)Tc-D-D3 was mainly distributed in the
      liver, kidney and lung, and less in the brain tissue and muscle. CONCLUSIONS:
      (99m)Tc-D-D3 antibody not only had high radiochemical purity, but also had good
      stability both in vitro and in vivo, and maintained good immunological activity.
      (99m)Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood
      radioactivity decreased rapidly. Thus, (99m)Tc-D-D3 is conducive to the
      radioimmunoimaging of SCLC.

PMID- 23557568
TI  - Effect of noninvasive positive pressure ventilation on weaning success in
      patients receiving invasive mechanical ventilation: a meta-analysis.
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NIPPV) has been proposed
      to shorten the duration of mechanical ventilation in intubated patients,
      especially those who fail initial weaning from invasive mechanical ventilation
      (IMV). However, there are also some discrepancies in terms of weaning success or
      failure, incidence of re-intubation, complications observed during study and
      patient outcomes. The primary objective of this update was to specifically
      investigate the role of NIPPV on facilitating weaning and avoiding re-intubation
      in patients intubated for different etiologies of acute respiratory failure, by
      comparing with conventional invasive weaning approach. METHODS: We searched
      randomized controlled trials (RCTs) comparing noninvasive weaning of early
      extubation and immediate application of NIPPV with invasive weaning in intubated
      patients from PubMed, Embase, Cochrane Central Register of Controlled Trials, Web
      of Knowledge and Springerlink databases. Records from conference proceedings and
      reference lists of relevant studies were also identified. RESULTS: A total of 11
      RCTs with 623 patients were available for the present analysis. Compared with
      IMV, NIPPV significantly increased weaning success rates (odds ratio (OR): 2.50,
      95% confidence interval (CI): 1.46 - 4.30, P = 0.0009), decreased mortality (OR:
      0.39, 95%CI: 0.20 - 0.75, P = 0.005), and reduced the incidence of ventilator
      associated pneumonia (VAP) (OR: 0.17, 95%CI: 0.08 - 0.37, P < 0.00001) and
      complications (OR: 0.22, 95%CI: 0.07 - 0.72, P = 0.01). However, effect of NIPPV
      on re-intubation did not reach statistical difference (OR: 0.61, 95%CI: 0.33 -
      1.11, P = 0.11). CONCLUSIONS: Early extubation and immediate application of NIPPV
      is superior to conventional invasive weaning approach in increasing weaning
      success rates, decreasing the risk of mortality and reducing the incidence of VAP
      and complications, in patients who need weaning from IMV. However, it should be
      applied with caution, as there is insufficient beneficial evidence to definitely
      recommend it in terms of avoiding re-intubation.

PMID- 23557569
TI  - Citrate versus unfractionated heparin for anticoagulation in continuous renal
      replacement therapy.
AB  - BACKGROUND: Unfractionated heparin is the most commonly used anticoagulant in
      continuous renal replacement therapy (CRRT), but it can increase the risk of
      bleeding. Citrate is a promising substitute. Our study was to assess the efficacy
      and safety of citrate versus unfractionated heparin in CRRT. METHODS: We searched
      the MEDLINE, the EMBASE, the Cochrane Central Register of Controlled Trials, and
      the China National Knowledge Infrastructure Database until up to November 2011
      for randomized controlled trials comparing citrate with unfractionated heparin in
      adult patients with acute kidney injury prescribed CRRT. The primary outcome was
      mortality and the secondary outcomes included circuit survival, control of
      uremia, risk of bleeding, transfusion rates, acid-base statuses, and disturbance
      of sodium and calcium homeostasis. RESULTS: Four trials met the inclusion
      criteria. Meta-analysis found no significant difference between two
      anticoagulants on mortality. Less bleeding and more hypocalcemic episodes were
      with citrate. Citrate was superior or comparable to unfractionated heparin in
      circuit life. CONCLUSIONS: Citrate anticoagulation in CRRT seems to be superior
      in reducing bleeding risk and with a longer or similar circuit life, although
      there is more metabolic derangement. Mortality superiority has not been approved.

PMID- 23557570
TI  - Stress-induced growth-differentiation factor 15 plays an intriguing role in
      cardiovascular diseases.
AB  - OBJECTIVE: To provide an overview of the current knowledge of growth
      differentiation factor 15 (GDF-15) in heart disease. DATA SOURCES: To identify
      relevant publications, we searched PubMED database combining the textual terms of
      heart, cardiac, cardiovascular disease with GDF-15. STUDY SELECTION: Well
      controlled, relatively large-scale, retrospective studies as well as meaningful
      individual cases were all selected as materials. RESULTS: GDF-15 is a distant
      member of the transforming growth factor-beta cytokine superfamily. In
      myocardium, GDF-15 is weakly expressed under physiological conditions. However,
      its expression level is increased in response to pathological stress. Growing
      evidence indicate that elevated levels of GDF-15 is a promising prognostic
      biomarker in cardiovascular diseases. Moreover, GDF-15 exhibits the properties of
      endogenous anti-hypertrophy of cardiomyocytes and protecting the heart suffering
      from ischemia and reperfusion insult. CONCLUSION: Ve GDF-15 may be a promising
      biomarker for evaluation and management of patient with cardiovascular diseases,
      and have potential protective properties on myocardium.

PMID- 23557571
TI  - Clinical utilization of microembolus detection by transcranial Doppler sonography
      in intracranial stenosis-occlusive disease.
AB  - OBJECTIVE: To discuss the clinical ultiliazation and significance of microembolus
      detection by transcranial Doppler (TCD) sonography in intracranial stenosis
      occlusive disease. DATA SOURCES: All related articles in this review were mainly
      searched from PubMed published in English from 1996 to 2012 using the terms of
      microembolic signal, transcranial Doppler, intracranial stenosis, stroke. STUDY
      SELECTION: Original articles and reviews were selected if they were related to
      the clinical utilization of microembolus detection in intracranial stenosis
      occlusive disease. RESULTS: Intracranial stenosis is a significant cause of
      cerebral emboli, and microembolus detection by TCD sonography were widely used in
      exploring the mechanisms of ischemic stroke with intracranial stenosis (including
      the middle cerebral artery stenosis and the vertebral-basilar stenosis),
      evaluating the prognosis of acute stroke, evaluating the therapeutic effects, and
      predicting the recurrent events of stroke. CONCLUSION: Microembolus detection by
      TCD sonography plays an important role in the cerebral ischemic stroke patients
      with intracranial stenosis.

PMID- 23557572
TI  - Biphasic regulation of hydrogen sulfide in inflammation.

PMID- 23557573
TI  - Rapamycin in fibrotic diseases: beneficial or detrimental agent?

PMID- 23557574
TI  - Important immunohistochemical markers for identifying sweat glands.

PMID- 23557575
TI  - Receiver operating characteristic curve analysis for image quality in the
      detection of solitary pulmonary nodules on high resolution paper prints versus
      dry laser film.

PMID- 23557576
TI  - A hybrid technique: intra-arterial catheter-directed thrombolysis following the
      recanalization of superior mesenteric artery in acute mesenteric ischemia.

PMID- 23557577
TI  - Intrabiliary rupture of hepatic hydatid cysts: results of 10 years' experience.

PMID- 23557578
TI  - Successful salvage in a scalp avulsion through unilateral microvascular
      anastomosis.

PMID- 23557579
TI  - A solitary fibrous tumor in the pancreas.

PMID- 23557580
TI  - Primary diffuse intraosseous meningioma.

PMID- 23557581
TI  - Renal sympathetic denervation for the treatment of resistant hypertension with
      chronic renal failure: first-in-man experience.

PMID- 23557582
TI  - Endoscopic treatment of thoracic tracheal stenosis with T-tube through
      tracheotomy opening in six patients.

PMID- 23557583
TI  - Moxifloxacin-induced multiple organ dysfunction possibly related to mutations in
      several genes involved in drug metabolism pathways.

PMID- 23557584
TI  - Pacemaker implantation in a patient with noncompaction and aneurysm of right
      ventricular combination with postclosure of atrial septal defect.

PMID- 23557585
TI  - Triple cusps replacement for active aortic endocarditis.

PMID- 23557586
TI  - Slow magnetic relaxation in Co(III)-Co(II) mixed-valence dinuclear complexes with
      a Co(II)O5X (X = Cl, Br, NO3) distorted-octahedral coordination sphere.
AB  - The reaction of the multisite coordination ligand (LH4) with CoX2.nH2O in the
      presence of tetrabutylammonium hydroxide affords a series of homometallic
      dinuclear mixed-valence complexes, [Co(III)Co(II)(LH2)2(X)(H2O)](H2O)m (1, X = Cl
      and m = 4; 2, X = Br and m = 4; 3, X = NO3 and m = 3). All of the complexes have
      been structurally characterized by X-ray crystallography. Both cobalt ions in
      these dinuclear complexes are present in a distorted-octahedral geometry.
      Detailed magnetic studies on 1-3 have been carried out. M vs H data at different
      temperatures can be fitted with S = 3/2, the best fit leading to D(3/2) = -7.4
      cm(-1), |E/D| < 1 * 10(-3), and g = 2.32 for 1 and D(3/2) = -9.7 cm(-1), |E/D| <1
      * 10(-4), and g = 2.52 for 2. In contrast to 1 and 2, M vs H data at different
      temperatures suggest that compound 3 has comparatively little magnetic
      anisotropy. In accordance with the large negative D values observed for compounds
      1 and 2, they are single-molecule magnets (SMMs) and exhibit slow relaxation of
      magnetization at low temperatures under an applied magnetic field of 1000 Oe with
      the following energy barriers: 7.9 cm(-1) (tauo = 6.1 * 10(-6) s) for 1 and 14.5
      cm(-1) (tauo = 1.0 * 10(-6) s) for 2. Complex 3 does not show any SMM behavior,
      as expected from its small magnetic anisotropy. The tauo values observed for 1
      and 2 are much larger than expected for a SMM, strongly suggesting that the
      quantum pathway of relaxation at very low temperatures is not fully suppressed by
      the effects of the applied field.

PMID- 23557587
TI  - Rotational atherectomy for left main coronary artery disease in octogenarians:
      transradial approach in a tertiary center and literature review.
AB  - OBJECTIVES: The aim of this study was to appreciate the safety and effectiveness
      of transradial percutaneous coronary intervention (PCI) with rotational
      atherectomy for highly calcified left main coronary artery (LMCA) disease in
      octogenarians. BACKGROUND: Conventional surgery is still considered the preferred
      management for LMCA disease; but, when the lesion is severely calcified, and the
      patient is unsuitable for surgery, the interventional cardiologist faces a
      complex PCI traditionally approached by femoral access. METHODS: Between June
      2004 and December 2010, octogenarians with calcified LMCA disease who were
      primary denied for surgical revascularization were enrolled. Procedural success
      and major adverse cerebral and cardiovascular events (MACCE) including death,
      nonfatal myocardial infarction, target lesion revascularization (TLR), or stroke
      during long-term follow-up were evaluated. RESULTS: Forty-two consecutive
      patients >=80 years had undergone stenting for calcified LMCA disease (13 with
      rotational atherectomy, the "Rota" group, and 29 without rotational atherectomy,
      the "without Rota" group). Procedural success was good (92.3% vs. 96.6%,
      respectively, p = NS). Mean follow-up time was 25.7 +/- 21.4 and 28 +/- 32.3
      months, respectively. There was a TLR in 25% and 11.1%, respectively; p = NS. No
      difference was detected in terms of overall in-hospital or long-term mortality or
      MACCE. CONCLUSION: Rotational atherectomy followed by stent implantation by
      transradial approach, when applied to heavily calcified lesions, appeared to be a
      safe and effective strategy for the treatment of LMCA disease in octogenarians
      who were refused for surgery.

PMID- 23557588
TI  - Haemodynamic analysis of the effect of different types of plaques in the left
      coronary artery.
AB  - PURPOSE: Coronary plaque has been shown to directly affect the blood parameters,
      however, haemodynamic variations based on the plaque configuration has not been
      studied. In this study we investigate the haemodynamic effects of various types
      of plaques in the left coronary bifurcation. METHODS: Eight types of plaque
      configurations were simulated and located in various positions in the left main
      stem, the left anterior descending and left circumflex to produce a >50%
      narrowing of the coronary lumen. We analyse and characterise haemodynamic effects
      caused by each type of plaque. Computational fluid dynamics was performed to
      simulate realistic physiological conditions that reveal the in vivo cardiac
      haemodynamics. Velocity, wall shear stress (WSS) and pressure gradient (PSG) in
      the left coronary artery were calculated and compared in all plaque
      configurations during cardiac cycles. RESULTS: Our results showed that the
      highest velocity and PSG were found in the type of plaque configuration which
      involved all of the three left coronary branches. Plaques located in the left
      circumflex branch resulted in highly significant changes of the velocity, WSS and
      PSG (p<0.001) when compared to the other types of plaque configurations.
      CONCLUSION: Our analysis provides an insight into the distribution of plaque at
      the left bifurcation, and corresponding haemodynamic effects, thus, improving our
      understanding of atherosclerosis.

PMID- 23557589
TI  - Lipid synthesis and processing proteins ABHD5, PGRMC1 and squalene synthase can
      serve as novel immunohistochemical markers for sebaceous neoplasms and
      differentiate sebaceous carcinoma from sebaceoma and basal cell carcinoma with
      clear cell features.
AB  - BACKGROUND: Sebaceous carcinoma represents a rare and potentially fatal adnexal
      malignancy. Poorly-differentiated sebaceous carcinoma consisting of infiltrative
      basaloid tumor cells with inapparent lipid vesicles can mimic basal cell
      carcinoma (BCC). Conversely, other epithelial tumors can exhibit clear cell
      histopathology and mimic sebaceous carcinoma. At the present time,
      immunohistochemical markers unique for sebaceous carcinoma are limited. METHODS:
      We evaluated the expression of three lipid synthesis/processing protein markers
      alpha/beta hydrolase domain-containing protein 5 (ABHD5), progesterone receptor
      membrane component-1 (PGRMC1) and squalene synthase (SQS) in sebaceous carcinoma
      and investigated their utility in differentiating sebaceous tumors from BCC with
      clear cell features. Immunohistochemistry was performed on 23 sebaceous
      carcinomas, 14 sebaceomas and 14 BCCs with clear cell features. RESULTS: In
      sebaceous carcinomas, ABHD5 showed dispersed, cytoplasmic punctate and/or
      vesicular staining (n = 19/23, 83%), while PGRMC1 and SQS each showed vesicular
      and membranous staining in tumor cells (n = 22/23, 96%). In all sebaceomas, these
      markers highlighted tightly clustered lipid vesicles in sebocytes. All BCCs with
      clear cell features were negative for these three markers. CONCLUSION: ABHD5,
      PGRMC1 and SQS are novel markers for sebaceous carcinoma and can reliably
      distinguish sebaceous neoplasms from non-sebaceous tumors, specifically BCC with
      clear cell features.

PMID- 23557590
TI  - Estrogen receptor protein content is different in abdominal than gluteal
      subcutaneous adipose tissue of overweight-to-obese premenopausal women.
AB  - OBJECTIVE: Premenopausal women demonstrate a distinctive gynoid body fat
      distribution and circulating estrogen status is associated with the maintenance
      of this adiposity patterning. Estrogen's role in modulation of regional adiposity
      may occur through estrogen receptors (ERs), which are present in human adipose
      tissue. The purpose of this study was to determine regional differences in the
      protein content of ERalpha, ERbeta, and the G protein-coupled estrogen receptor
      (GPER) between the abdominal (AB) and gluteal (GL) subcutaneous adipose tissue of
      overweight-to-obese premenopausal women. MATERIALS/METHODS: Biopsies of the
      subcutaneous AB and GL adipose tissue were performed in 15 premenopausal women (7
      Caucasian/8 African American, 25.1 +/- 1.8 years, BMI 29.5 +/- 0.5kg/m(2)).
      Adipose tissue protein content was measured by western blot analysis and
      correlation analyses were conducted to assess the relationship between ER protein
      content and anthropometric indices/body composition measurements. RESULTS: We
      found that ERalpha protein was higher in AB than GL (AB 1.0 +/- 0.2 vs GL 0.67 +/
      0.1 arbitrary units [AU], P=0.02), ERbeta protein was higher in GL than AB (AB
      0.78 +/- 0.12 vs GL 1.3 +/- 0.2 AU, P=0.002), ERalpha/ERbeta ratio was higher in
      AB than GL (AB 1.9 +/- 0.4 vs GL 0.58 +/- 0.08 AU, P=0.007), and GPER protein
      content was similar in AB and GL (P=0.80) subcutaneous adipose tissue. Waist-to
      hip ratio was inversely related to gluteal ERbeta (r(2)=0.315, P=0.03) and
      positively related to gluteal ERalpha/ERbeta ratio (r(2)=0.406, P=0.01).
      CONCLUSIONS: These results indicate that depot specific ER content may be an
      important underlying determinant of regional effects of estrogen in upper and
      lower body adipose tissue of overweight-to-obese premenopausal women.

PMID- 23557592
TI  - Metabolic syndrome may be associated with increased arterial stiffness even in
      the absence of hypertension: a study in 84 cases and 82 controls.
AB  - OBJECTIVE: To evaluate the hemodynamic characteristics of metabolic syndrome
      (MetS) in the absence and presence of hypertension. MATERIALS/METHODS: Altogether
      166 subjects without previously diagnosed cardiovascular disease, diabetes, or
      antihypertensive medication, were allocated to four groups: control, hypertension
      only, MetS without hypertension, and MetS with hypertension (mean age 44-46
      years). Cut-point for hypertension was blood pressure >=140/90 mmHg. Other
      criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables
      were measured using whole-body impedance cardiography and pulse wave analysis.
      RESULTS: Pulse wave velocity was higher in hypertensive and normotensive subjects
      with MetS than controls (p<0.05), and in the hypertensive MetS group than
      subjects with hypertension only (p<0.05). Aortic pulse pressure was higher in the
      two hypertensive groups than the two normotensive groups (p<0.05). Systemic
      vascular resistance index was higher in the hypertensive than normotensive MetS
      group (p<0.05), and in the group with hypertension alone than in controls
      (p<0.05). Heart rate was higher in the hypertensive Mets group than in controls
      and subjects with hypertension only (p<0.05). Cardiac index did not differ, while
      stroke index was lower in both groups with MetS than groups without MetS.
      Augmentation pressure was higher in the hypertensive MetS group than in controls
      and normotensive MetS group (p<0.05). CONCLUSIONS: Pulse wave velocity, an
      acknowledged marker of arterial stiffness, was associated with MetS even in the
      absence of hypertension. This emphasizes the importance of the prevention and
      treatment of MetS.

PMID- 23557593
TI  - Employability in health profession education: not resting on our laurels.

PMID- 23557591
TI  - Effects of prediabetes and diabetes on left ventricular and coronary
      microvascular functions.
AB  - BACKGROUND: Coronary flow reserve (CFR) provides independent prognostic
      information in diabetic patients with known or suspected coronary artery disease.
      However, there have been no substantial data to evaluate CFR in prediabetics.
      Accordingly, we aimed to evaluate CFR in subjects with prediabetes using second
      harmonic transthoracic Doppler echocardiography. METHODS AND RESULTS: We measured
      CFR of 65 subjects with prediabetes, 45 patients with overt type 2 diabetes, and
      43 sex and age matched normoglycemic healthy subjects with normal glucose
      tolerance. Ages, gender, existence of hypertension or hypercholesterolemia,
      smoking status were similar among the groups. CFR was significantly lower in
      diabetics (2.15 +/- 0.39) than in prediabetics (2.39 +/- 0.45) and controls (2.75
      +/- 0.35); in addition, it was significantly lower in prediabetics than controls.
      Only 2 (5%) of control subjects had abnormal CFR (<2) but 11 (17%) prediabetic
      subjects and 19 (42%) diabetic patients had abnormal CFR. We found that only age
      (beta=-0.31, P<0.01) and presence of the diabetes (beta=-0.57, P<0.01) were
      significant predictors of lower CFR in a multivariable model that adjusted for
      other variables. CFR was significantly and inversely correlated with age (r=
      0.15, P=0.04), fasting glucose level (r=-0.27, P=0.001), postprandial glucose
      level (r=0.43, P<0.001), hemoglobin A1C level (r=-0.34, P<0.001), LDL cholesterol
      level (r=0.22, P=0.009), mitral A velocity (r=-0.27, P=0.001) and Tei index (r=
      0.19, P=0.02), whereas mitral E/A ratio, mitral Em (r=0.18, P=0.02), mitral Em/Am
      ratio (r=0.23, P=0.004) were significantly and positively correlated with CFR.
      CONCLUSION: CFR is impaired in subjects with prediabetics, but this impairment is
      not as severe as that in diabetics.

PMID- 23557594
TI  - Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc
      analysis of RECOVER.
AB  - BACKGROUND: Non-motor symptoms of Parkinson's disease (PD) represent major causes
      of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal
      system, was the first prospective controlled trial to use the Non-Motor Symptoms
      Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non
      motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo,
      and the "Sleep/fatigue" and "Mood/apathy" domains. This post hoc analysis further
      characterizes the effects of rotigotine on sleep/fatigue and mood/apathy.
      METHODS: Patients with PD and unsatisfactory early-morning motor impairment were
      randomized to transdermal patches of rotigotine (2-16 mg/24 h) or placebo.
      Treatment was titrated to optimal dose over 1-8 weeks, maintained for 4 weeks.
      The NMSS was assessed at baseline and end of treatment. Post hoc analyses are
      presented for individual items of the "Sleep/fatigue" and "Mood/apathy" domains.
      The interpretation of p-values is considered exploratory in nature. RESULTS: Of
      287 patients randomized, NMSS data were available for 267 patients (178
      rotigotine, 89 placebo). Within the "Sleep/fatigue" domain there was a
      significant difference, in favor of rotigotine, in change from baseline score in
      1 of 5 items: "fatigue (tiredness) or lack of energy" (ANCOVA, p < 0.0001).
      Within the "Mood/apathy" domain, there were significant differences in favor of
      rotigotine in 4 of 7 items: "lost interest in surroundings" (p < 0.0001), "lost
      interest in doing things" (p < 0.0001), "seems sad or depressed" (p < 0.01), and
      "difficulty experiencing pleasure" (p < 0.05). CONCLUSIONS: Rotigotine
      transdermal system may improve non-motor symptoms such as fatigue, symptoms of
      depression, anhedonia, and apathy in patients with PD; further prospective
      controlled studies are required to confirm this post hoc analysis.

PMID- 23557595
TI  - Effect of muscle fatigue and physical activity level in motor control of the gait
      of young adults.
AB  - The aim of this study was to analyze the effect of muscle fatigue in active and
      inactive young adults on the kinematic and kinetic parameters of normal gait and
      obstacle crossing. Twenty male subjects were divided into active (10) and
      inactive (10), based on self-reported physical activity. Participants performed
      three trials of two tasks (normal gait and obstacle crossing) before and after a
      fatigue protocol, consisting of repeated sit-to-stand transfers until the
      instructed pace could no longer be maintained. MANOVAs were used to compare
      dependent variables with the following factors: physical activity level, fatigue
      and task. The endurance time in the fatigue protocol was lower for the inactive
      group. Changes of gait parameters with fatigue, among which increased step width
      and increased stride speed were the most consistent, were independent of task and
      physical activity level. These findings indicate that the kinematic and kinetic
      parameters of gait are affected by muscle fatigue irrespective of the physical
      activity level of the subjects and type of gait. Inactive individuals used a
      slightly different strategy than active individuals when crossing an obstacle,
      independently of muscle fatigue. 

PMID- 23557596
TI  - The personal health record paradox: health care professionals' perspectives and
      the information ecology of personal health record systems in organizational and
      clinical settings.
AB  - BACKGROUND: Despite significant consumer interest and anticipated benefits,
      overall adoption of personal health records (PHRs) remains relatively low.
      Understanding the consumer perspective is necessary, but insufficient by itself.
      Consumer PHR use also has broad implications for health care professionals and
      organizational delivery systems; however, these have received less attention. An
      exclusive focus on the PHR as a tool for consumer empowerment does not adequately
      take into account the social and organizational context of health care delivery,
      and the reciprocal nature of patient engagement. OBJECTIVE: The purpose of this
      study was to examine the experiences of physicians, nurses, and pharmacists at
      the Department of Veterans Affairs (VA) using an organizationally sponsored PHR
      to develop insights into the interaction of technology and processes of health
      care delivery. The conceptual framework for the study draws on an information
      ecology perspective, which recognizes that a vibrant dynamic exists among
      technologies, people, practices, and values, accounting for both the values and
      norms of the participants and the practices of the local setting. The study
      explores the experiences and perspectives of VA health care professionals related
      to patient use of the My HealtheVet PHR portal and secure messaging systems.
      METHODS: In-depth interviews were conducted with 30 VA health care professionals
      engaged in providing direct patient care who self-reported that they had
      experiences with at least 1 of 4 PHR features. Interviews were transcribed,
      coded, and analyzed to identify inductive themes. Organizational documents and
      artifacts were reviewed and analyzed to trace the trajectory of secure messaging
      implementation as part of the VA Patient Aligned Care Team (PACT) model. RESULTS:
      Study findings revealed a variety of factors that have facilitated or inhibited
      PHR adoption, use, and endorsement of patient use by health care professionals.
      Health care professionals' accounts and analysis of organizational documents
      revealed a multidimensional dynamic between the trajectory of secure messaging
      implementation and its impact on organizational actors and their use of
      technology, influencing workflow, practices, and the flow of information. In
      effect, secure messaging was the missing element of complex information ecology
      and its implementation acted as a catalyst for change. Secure messaging was found
      to have important consequences for access, communication, patient self-report,
      and patient/provider relationships. CONCLUSIONS: Study findings have direct
      implications for the development and implementation of PHR systems to ensure
      adequate training and support for health care professionals, alignment with
      clinical workflow, and features that enable information sharing and
      communication. Study findings highlight the importance of clinician endorsement
      and engagement, and the need to further examine both intended and unintended
      consequences of use. This research provides an integral step toward better
      understanding the social and organizational context and impact of PHR and secure
      messaging use in clinical practice settings.

PMID- 23557597
TI  - Effect of diet delivered various concentrations of double-stranded RNA in
      silencing a midgut and a non-midgut gene of Helicoverpa armigera.
AB  - Ribonucleic acid interference (RNAi) is a sequence-specific gene silencing
      mechanism induced by double-stranded RNA (dsRNA). Recently, RNAi has gained
      popularity as a reverse genetics tool owing to its tremendous potential in insect
      pest management, which includes Helicoverpa armigera. However, its efficiency is
      mainly governed by dsRNA concentration, frequency of application, target gene,
      etc. Therefore, to obtain a robust RNAi response in H. armigera, we evaluated
      various concentrations of dsRNA and its frequency of applications delivered
      through diet in silencing a midgut gene, chymotrypsin and a non-midgut gene,
      juvenile hormone acid methyl transferase (jhamt) of H. armigera. The extent of
      target gene silencing was determined by employing reverse transcription
      quantitative real-time polymerase chain reaction (RT-qPCR). Our study revealed
      four significant findings: (i) single application of dsRNA elicited a delayed and
      transient silencing, while multiple applications resulted in early and persistent
      silencing of the above genes; (ii) silencing of the non-midgut gene (jhamt)
      through diet delivered dsRNA revealed prevalence of systemic silencing probably
      due to communication of silencing signals in this pest; (iii) the extent of
      silencing of chymotrypsin was positively correlated with dsRNA concentration and
      was negatively correlated with jhamt; (iv) interestingly, over-expression (15-18
      folds) of an upstream gene, farnesyl diphosphate synthase (fpps), in juvenile
      hormone (JH) biosynthetic pathway at higher concentrations of jhamt dsRNA was the
      plausible reason for lesser silencing of jhamt. This study provides an insight
      into RNAi response of target genes, which is essential for RNAi design and
      implementation as a pest management strategy.

PMID- 23557599
TI  - Word frequency, function words and the second gavagai problem.
AB  - The classic gavagai problem exemplifies the difficulty to identify the referent
      of a novel word uttered in a foreign language. Here, we consider the reverse
      problem: identifying the referential part of a label. Assuming "gavagai"
      indicates a rabbit in a foreign language, it may very well mean "a rabbit" or
      "that rabbit". How can a learner know whether rabbit is actually said "vagai",
      "gava" or "gavagai"? Here, we report evidence suggesting that infants can
      identify potential function words on the basis of their high frequency and avoid
      considering them when associating labels and referents. In three experiments, 17
      month-old infants were first exposed to an artificial speech stream where
      frequent and infrequent syllables alternated (e.g., ... gibuvokugifevodegita...).
      Infants then saw a novel object and heard the repetition of a bisyllabic label
      consisting of one frequent and one infrequent syllable (e.g., vomu). The frequent
      syllable was the initial syllable of the label in Experiment 1 and the final in
      Experiments 2 and 3. We then presented infants with both the previous and now
      familiar object and a novel object. We asked whether infants would be more likely
      to orient first towards the familiar object when hearing a label with a new
      frequent and the previous infrequent syllables (e.g., gimu), or when hearing a
      label with a new infrequent and the previous frequent syllables (e.g., vona).
      Results suggest that the infrequent syllable was associated more strongly with
      the object, than the frequent one, only when the perceived position of the
      frequent syllable was constant all along the experiment.

PMID- 23557598
TI  - Sources of heterogeneity in human monocyte subsets.
AB  - Human monocytes are commonly defined and discriminated by the extent of their
      cell surface expression of CD14 and CD16, with associated differences in function
      and phenotype related to the intensity of expression of these markers. With
      increasing interest into the function and behaviour of monocytes, it is important
      to have a clear understanding of how differing strategies of analysis can affect
      results and how different protocols and population backgrounds can affect this
      highly morphogenic cell type. Using PBMCs from populations with differing
      ethnicities and histories of parasite exposure we have characterized monocyte
      phenotype based on intensity of CD14 and CD16 expression. Using the surface
      markers HLA-DR, CCR2 and CX3CR1, we compared monocyte phenotype between
      populations and further assessed changes in monocytes with freezing and thawing
      of PBMCs. Our results reveal that there is a progression of surface marker
      expression based on intensity of CD14 or CD16 expression, stressing the
      importance of careful gating of monocyte subtypes. Freezing and thawing of the
      PBMCs has no effect generally on the monocytes, although it does lead to a
      decrease in CD16 and CX3CR1 expression. We show that there are differences in the
      monocyte populations based on ethnicity and history of exposure to the common
      parasites Plasmodium falciparum and Schistosoma haematobium. This study
      highlights that blood monocytes consist of a continuous population of cells,
      within which the dominant phenotype may vary dependent on the background of the
      study population. Comparing results from monocyte studies therefore needs to be
      done with great care, as ethnic background of donor population, gating strategy
      and processing of PBMCs may all have an effect on outcome of monocyte phenotype.

PMID- 23557600
TI  - Direct intranigral administration of an ubiquitin proteasome system inhibitor in
      rat: behavior, positron emission tomography, immunohistochemistry.
AB  - Several independent lines of research suggest that disruption of the ubiquitin
      proteasome system (UPS) may play a role in the pathophysiology of Parkinson's
      disease. Direct intracerebral injection of UPS inhibitors (e.g. lactacystin) in
      animals has consistently produced important features of the disease. In this
      study, a range of lactacystin doses (0.5, 1, 2, 10 and 20 MUg) were injected into
      the right substantia nigra in rats to determine the ideal dose required to
      produce a robust and specific lesion of the dopamine nigro-striatal system and
      motor deficits. Motor behavior, assessed with the tapered ledged beam task, was
      severely affected in animals that received high doses (10 and 20 MUg) but only
      mild, impairments were observed in animals that received low doses (0.5, 1, and 2
      MUg). Positron emission tomography was performed with a dedicated small animal
      scanner on the rats following the injection of the radio-labeled tracer (+/
      )[(11)C]dihydrotetrabenazine (DTBZ) which labels vesicular monoamine transporter
      type 2. Severe loss of [(11)C]DTBZ binding in the ipsilateral striatum was
      observed in the higher dose groups and mild loss was observed in the low dose
      groups. Stereological cell counting of tyrosine hydroxylase immunoreactive cells
      in the substantia nigra and the ventral tegmental area indicated a dose dependent
      loss of dopaminergic neurons. Significant correlations were found between the
      behavioral motor deficits, striatal [(11)C]DTBZ binding and cell counts of
      tyrosine hydroxylase immunoreactive cells. Taken together these results indicate
      that intranigral injection of lactacystin produces dose dependent effects on the
      dopamine nigro-striatal system and a dose of 10 MUg will produce a consistent
      severe lesion.

PMID- 23557601
TI  - Screening and evaluation of traditional Chinese medicine by microarray expression
      analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza is a Chinese medicinal herb,
      which is widely used for the treatment of cardiovascular disorders. In this
      article, we investigated the effects of Salvia miltiorrhiza and its hydrophilic
      and lipophilic components (HCS and LCS) on human umbilical vein endothelial cells
      (HUVECs), and the molecular mechanism was explored by microarray gene expression
      profiling. MATERIALS AND METHODS: Cell proliferation and migration were used to
      evaluate the angiogenic effects of HCS, LCS and total extract of Salvia
      miltiorrhiza (TES). Microarray technology was applied to detect the gene
      expression of HUVECs treated with TES, HCS and LCS. Besides, quantitative real
      time PCR was used to verify the microarray results. RESULTS: Our results showed
      that LCS inhibited the proliferation and migration of HUVECs, HCS promoted the
      proliferation and migration of HUVECs, and TES did not affect the viability of
      HUVECs at the concentration of 5 ug/mL. From the result of principle component
      analysis (PCA) of microarray data, the effect of LCS on HUVECs was significantly
      different from the other components. Moreover, there were more differentially
      expression genes in LCS group than in the other groups, which meant LCS had a
      strong influence on HUVECs. Compared with untreated cells, 511 significantly
      changed genes had been detected in LCS treated cells and 236 (approximately 46%)
      of them were up-regulated. The mRNA expression of IL-6 was found to be increased
      significantly in LCS group. CONCLUSIONS: In Salvia miltiorrhiza, HCS and LCS had
      opposite effects on HUVECs. LCS showed significantly inhibitory action on HUVECs
      proliferation and migration. It was proposed that LCS could apply in the diseases
      caused by vascular anomaly hyperplasia. In the mechanism of action of LCS on
      HUVECs, the pathways of ErbB, MAPK, p53, oxidative phosphorylation and
      inflammatory response were involved.

PMID- 23557602
TI  - An inverse correlation of serum angiogenin levels with estimated glomerular
      filtration rate in systemic sclerosis patients with renal dysfunction.

PMID- 23557603
TI  - Arousability as a predictor of sexual risk behaviours in African-American
      adolescent women.
AB  - This study examined the impact of sexual excitation (arousability) on sexual risk
      taking behaviours in a community sample of African-American adolescent women. A
      sample of 701 African-American adolescent women completed measures examining
      their propensity for sexual arousal, impulsivity and sexual behaviour. Compared
      with women with a lower propensity for sexual arousability, women with a higher
      propensity reported a greater number of sexual partners, more inconsistent condom
      use, a greater likelihood of having engaged in sexual intercourse with 'risky'
      partners, and sex while high on alcohol or drugs. These results indicate that
      women who have a greater propensity to become sexually aroused in a variety of
      situations may be at a greater risk for contracting HIV or sexually transmissible
      infections relative to women with a lower propensity for arousal. This suggests
      that individual differences in the propensity to become sexually aroused should
      be considered when developing intervention approaches targeting young African
      American women.

PMID- 23557604
TI  - beta-Arrestin signal complex plays a critical role in adipose differentiation.
AB  - beta-Arrestins were identified as scaffold-proteins that have the capacity to
      desensitize G protein-coupled receptors. However, it has been found that beta
      arrestins activate signaling pathways independent of G protein activation. The
      diversity of these signaling pathways has also been recognized for receptor
      tyrosine kinase. The aim of the present study was to validate the beta-arrestin
      dependent signaling mechanism(s) responsible for regulation of adipogenesis. Two
      signal models were selected, ghrelin and insulin, based on its beta-arrestin
      associated Akt activity. Herein, we found that beta-arrestin 1 and 2 were
      essential molecules for adipocyte differentiation. More specifically, the role of
      these scaffolding proteins was demonstrated by depletion of beta-arrestin 1 and 2
      during ghrelin-induced adipogenesis in 3T3-L1 cells, which decreased the
      adipocyte differentiation and the expression levels of master regulators of
      early, the CCAAT/enhancer-binding protein beta (C/EBPbeta) and the CCAAT/enhancer
      binding protein delta (C/EBPdelta), and terminal, the peroxisome proliferator
      activated receptor (PPARgamma) and the CCAAT/enhancer-binding protein alpha
      (C/EBPalpha), adipogenesis. Accordingly ghrelin-induced Akt activity and its
      downstream targets, the mammalian target of rapamycin complex 1 (mTORC1) and the
      ribosomal protein S6 kinase beta-1 (S6K1), were inhibited by beta-arrestin 1 and
      2 siRNAs. By contrast, assays performed during insulin-activated adipogenesis
      showed an intensifying effect on the adipocyte differentiation as well as on the
      expression of C/EBPbeta, C/EBPdelta, PPARgamma and C/EBPalpha. The increase in
      insulin-induced adipogenesis by beta-arrestin knock-down was concomitant to a
      decrease in the insulin receptor susbtrate-1 (IRS-1) serine phosphorylation,
      proving the loss of the negative feedback loop on IRS-1/phosphoinositide 3-kinase
      (PI3K)/Akt. Therefore, beta-arrestins control the extent and intensity of the
      lipogenic and adipogenic factors associated to Akt signaling, although the
      mechanistic and functional principles that underlie the connection between
      signaling and beta-arrestins are specifically associated to each receptor type.

PMID- 23557605
TI  - Gas-phase self-assembly of highly ordered titania@graphene nanoflakes for
      enhancement in photocatalytic activity.
AB  - The gas-phase self-assembly of reduced graphene oxide (rGO) nanoflakes with
      highly ordered ultrafine titania (TiO2) particles was performed and the resultant
      hybrid material displayed an enhanced photocatalytic performance, both in
      producing hydrogen and in degrading dyes. Freshly synthesized TiO2 nanoparticles
      (~35 nm in equivalent mobility diameter) were quantitatively incorporated with
      nanoscale rGO (~36 nm in equivalent mobility diameter) in the form of TiO2/rGO
      hybrid nanoflakes (~31 nm in equivalent mobility diameter). The TiO2/rGO hybrid
      flakes were finally employed to evaluate its photocatalytic activity, and it was
      found that the ability to achieve hydrogen production and dye degradation was
      greater than that of a hybridized material from commercial p25-TiO2 and large
      rGO. This gas-phase self-assembly also enhanced the photocatalytic activity by
      applying different spark configurations to prepare ZnO, Au, or Ag particles
      incorporated with rGO nanoflakes.

PMID- 23557606
TI  - How minimal is ... minimal?

PMID- 23557607
TI  - Almanac 2012: Congenital Heart Disease. The National Society Journals Present
      selected research that has driven recent advances in clinical cardiology.
AB  - This Almanac highlights recent papers on congenital heart disease in the major
      cardiac journals. Over 100 articles are cited. Subheadings are used to group
      relevant papers and allow readers to focus on their areas of interest, but are
      not meant to be comprehensive for all aspects of congenital cardiac disease.

PMID- 23557608
TI  - The impact of physical activity on endothelial function in middle-aged and
      elderly subjects: the Ikaria study.
AB  - INTRODUCTION: Exercise training and physical activity (PA) have substantial
      vascular and cardiac health benefits. Ikaria Island has been recognised as having
      one of the highest longevity rates worldwide and a high percentage of healthy
      ageing. We examined the relationship between endothelial function and levels of
      habitual PA to evaluate the factors related to healthy ageing in this population.
      METHODS: The study was conducted on a subgroup population of the IKARIA study
      consisting of 185 middle-aged (40-65 years) and 142 elderly subjects (66-91
      years). Endothelial function was evaluated by ultrasound measurement of flow
      mediated dilatation (FMD). PA was evaluated using the shortened version of the
      self-reported International Physical Activity Questionnaire (IPAQ). Subjects in
      the low PA group (<500 MET/ min/week) were considered as physically inactive and
      the rest as active. RESULTS: In the overall study population FMD was inversely
      associated with age (r=-0.24, p<0.001) and middle-aged subjects had higher FMD
      compared with the elderly (6.26 +/- 3.31% vs. 5.21 +/- 2.95%, p=0.003). Multiple
      linear regression analysis revealed that among middle-aged subjects the
      physically active had higher FMD compared with the physically inactive.
      Physically active subjects in the middle-aged group showed higher FMD compared
      with the physically active elderly (p=0.008). However, there was no difference in
      FMD values between middle-aged inactive subjects and the elderly physically
      active (p=NS). CONCLUSION: The present study revealed that increased PA was
      associated with improved endothelial function in middle-aged subjects and that PA
      in elderly subjects can ameliorate the devastating effects of ageing on arterial
      wall properties.

PMID- 23557609
TI  - Quality of anticoagulation with warfarin across Kuwait.
AB  - INTRODUCTION: Warfarin is widely used in patients with non-valvular atrial
      fibrillation (AF) because it is effective in reducing thromboembolic
      complications. However, it has a narrow safe therapeutic window. We aimed to
      examine the frequency of maintaining this therapeutic window in daily practice.
      METHODS: We enrolled consecutive patients with non-valvular AF presenting to five
      busy general hospitals in Kuwait for regular international normalised ratio (INR)
      testing. Patients were required to be on warfarin for more than 3 months and to
      have had at least 5 INR measurements. We recorded up to 20 INR measurements per
      patient. Time in therapeutic range (TTR) was assessed by the Rosendaal method and
      the percentage of INR measurements in the therapeutic range was recorded.
      RESULTS: A total of 369 patients with non-valvular AF underwent 4392 INR
      measurements. (mean age 62.89 +/- 11 years, 56% women, 78% had hypertension and
      58% had diabetes). Mean duration of warfarin use was 13 +/- 9.1 months. Of all
      INR measurements, 47% were in the therapeutic range of 2-3 and TTR by Rosendaal
      method was 52.6%. CONCLUSIONS: The quality of anticoagulation with warfarin in
      non-selected daily practice in Kuwait is poor. This could have serious
      implications for patients' outcomes.

PMID- 23557610
TI  - Cardiorespiratory parameters of exercise capacity in a healthy Lithuanian
      population: the pilot study.
AB  - INTRODUCTION: The normative values of exercise capacity used for the
      interpretation of exercise testing results are influenced by a variety of
      internal and external factors specific to certain populations. Therefore, in
      clinical practice it is recommended that population-specific reference values be
      employed. Cardiorespiratory fitness norms have not yet been established for a
      healthy Lithuanian population over a wide age span. The purpose of the present
      study was to determine the main cardiorespiratory fitness parameters for healthy
      adults living in Lithuania and to compare these parameters with the reference
      values established for different foreign populations. METHODS: This was a cross
      sectional, community-based study involving 168 healthy adults aged from 20 to 60
      years who were randomly selected from the general population. All subjects
      performed a progressive incremental exercise test on the cycle ergometer. The
      main cardiorespiratory fitness parameters analysed were peak oxygen consumption
      (VO2peak), ventilatory anaerobic threshold, and peak heart rate (HRpeak).
      RESULTS: The average estimated VO2peak was 35.02 +/- 7.37 mL.kg(-1).min(-1) for
      men and 28.27 +/- 6.33 mL.kg(-1).min(-1) for women. According to the results
      presented by other authors, this parameter is approximately 9-22% lower compared
      to other populations in all age groups, with the exception of the 20-29 year old
      group who alone satisfied fair aerobic fitness criteria. The average age-related
      decline in VO2peak was 0.016 L.min(-1) per year for men and 0.011 L.min(-1) per
      year for women. However, age itself explained only 12-14% of the variance. After
      VO2peak was adjusted relative to body mass, the difference in the decline between
      men and women remained insignificant: VO2peak decrease was 0.34 mL.kg(-1).min(-1)
      per year for men (coefficient of determination R(2) 0.250) and 0.32 mL.kg(
      1).min(-1) per year for women (R(2) 0.330). A decline in peak heart rate of
      approximately 9 beats per minute was observed in each following age decade, which
      was well explained by the advancing age (R(2) 0.512 for men and R(2) 0.484 for
      women). CONCLUSIONS: Cardiorespiratory fitness parameters estimated for healthy
      adults living in Lithuania appeared to be lower compared to different foreign
      populations, despite the relatively similar general trends in the age-related
      decline in exercise capacity. Exercise testing laboratories and rehabilitation
      clinics in Lithuania may use these results in clinical practice when evaluating
      patients' exercise capacity, or as a promotional tool for physical activity in
      the general public.

PMID- 23557611
TI  - Distinct association of admission hyperglycemia with one-year adverse outcome in
      diabetic and non-diabetic patients with acute ST-elevation myocardial infarction.
AB  - INTRODUCTION: Both admission hyperglycemia (AH) and diabetes mellitus adversely
      affect the prognosis in acute coronary syndromes. We prospectively assessed the
      predictive role of AH in patients with acute ST-segment elevation myocardial
      infarction (STEMI). METHODS: Three hundred-one consecutive patients hospitalized
      for STEMI were enrolled. Patients were stratified into four groups based on their
      history of diabetes and the presence of AH (plasma glucose level >11.0 mmol/l or
      200 mg/dl). The pre-specified endpoint was the composite of all-cause mortality,
      non-fatal MI and stroke after one year follow up. RESULTS: The incidence of the
      endpoint was 19.6% (35 all-cause deaths, 21 non-fatal MIs, and 3 strokes). Non
      diabetic patients with AH exhibited a significantly higher incidence of the
      composite endpoint compared to those with neither diabetes nor AH (50% vs. 15.3%,
      log rank p<0.001) and diabetics with or without AH (50% vs. 17.2% vs. 19.3%, log
      rank p<0.05 for both). Ejection fraction (HR 0.946, p=0.007), treatment with
      primary percutaneous coronary intervention (HR=0.488, p=0.041), and AH in the
      absence of known diabetes (HR 2.207, p=0.043) were the only independent
      predictors of the endpoint. CONCLUSIONS: AH in non-diabetic STEMI patients is
      accompanied by a worse long-term prognosis compared to diabetics (with or without
      AH) or normoglycemic patients and constitutes a potent predictor of an adverse
      outcome.

PMID- 23557612
TI  - Six-minute walk test: an effective and necessary tool in modern cardiac
      rehabilitation.

PMID- 23557613
TI  - Medical error in clinical practice: "errare humanum est".

PMID- 23557614
TI  - Spontaneous recanalization of coronary occlusion: features with optical coherence
      tomography.

PMID- 23557615
TI  - Left atrial myxoma associated with mitral valve pathology in pregnancy.
AB  - We report a case of a left atrial myxoma associated with mitral valve
      regurgitation in a pregnant patient, describing the importance of
      transoesophageal or transthoracic echocardiography, preoperatively and during the
      operation, as a useful tool to rule out any associated valvular damage or mitral
      annular dilatation as an underlying cause of mitral regurgitation.

PMID- 23557617
TI  - Revealing infective endocarditis complications by echocardiography: the value of
      real-time 3D transesophageal echocardiography.
AB  - A 72-year-old patient was admitted to the Department of Cardiology of Emory
      University Hospital with the diagnosis of infective endocarditis. Two-dimensional
      transesophageal echocardiography (TEE) showed a vegetation attached to the
      posterior mitral valve leaflet that led to severe mitral regurgitation. Real-time
      3-dimensional TEE clearly identified the large posterior leaflet vegetation but
      additionally showed the perforated posterior mitral valve leaflet. Real time 3D
      TEE, and especially the large sector-focused data, allow for detailed
      identification of the mitral valve leaflets from both the atrial and the
      ventricular side. Those characteristics of real-time 3D TEE confer incremental
      value in assessing infective endocarditis lesions and complications.

PMID- 23557616
TI  - Idiopathic pulmonary arterial hypertension in a young patient with the Cohen
      syndrome.
AB  - We admitted a 16-year-old boy with the Cohen syndrome to our institution for
      increasing dyspnoea. Investigations revealed idiopathic pulmonary hypertension.
      He was commenced on bosentan and oral anticoagulation and was followed up for
      nearly 7 years, during which he was readmitted for dynamic measurements of
      pulmonary artery pressure. Despite initial improvement, the right heart pressures
      increased again and sildenafil was added. His final hospitalisation was due to
      increasing breathlessness and episodes of syncope. The addition of prostacyclin
      conferred no reduction in pulmonary artery pressure. The patient suffered a
      cardiac arrest and remained intubated for 2 weeks, during which Klebsiella
      pneumonia and superinfection with the H1N1 swine flu virus occurred. The patient
      died due to multi-organ failure, nearly 7 years after his initial diagnosis. The
      Cohen syndrome, its phenotype and clinical findings, and the incidence and
      treatment of pulmonary hypertension are discussed.

PMID- 23557620
TI  - Diabetes mellitus: a sweet-and-sour disease.

PMID- 23557618
TI  - Oral anticoagulation and implantation of cardiac rhythm management devices: is
      heparin a bridge too far?

PMID- 23557621
TI  - The cost-effectiveness of cardiovascular medicine: victims of our own success?

PMID- 23557622
TI  - Hansen's disease presenting with penile nodules.

PMID- 23557623
TI  - Mapping cation entry in photoreceptors and inner retinal neurons during early
      degeneration in the P23H-3 rat retina.
AB  - The proline-23-histidine line 3 (P23H-3) transgenic rat carries a human opsin
      gene mutation leading to progressive photoreceptor loss characteristic of human
      autosomal dominant retinitis pigmentosa. The aim of the present study was to
      evaluate neurochemical modifications in the P23H-3 retina as a function of
      development and degeneration. Specifically, we investigated the ion channel
      permeability of photoreceptors by tracking an organic cation, agmatine (1-amino-4
      guanidobutane, AGB), which permeates through nonspecific cation channels. We also
      investigated the activity of ionotropic glutamate receptors in distinct
      populations of bipolar, amacrine, and ganglion cells using AGB tracking in
      combination with macromolecular markers. We found elevated cation channel
      permeation in photoreceptors as early as postnatal day 12 (P12) suggesting that
      AGB labeling is an early indicator of impending photoreceptor degeneration.
      However, bipolar, amacrine, or ganglion cells displayed normal responses
      secondary to ionotropic glutamate receptor activation even at P138 when about one
      half of the photoreceptor layer was lost and apoptosis and gliosis were observed.
      These results suggest that possible therapeutic windows as downstream neurons in
      inner retina appear to retain normal function with regard to AGB permeation when
      photoreceptors are significantly reduced but not lost. 

PMID- 23557625
TI  - Posttraumatic stress disorder: what have we learned in 3000 years?

PMID- 23557624
TI  - Design, synthesis, and kinetic characterization of protein N-terminal
      acetyltransferase inhibitors.
AB  - The N-termini of 80-90% of human proteins are acetylated by the N-terminal
      acetyltransferases (NATs), NatA-NatF. The major NAT complex, NatA, and
      particularly the catalytic subunit hNaa10 (ARD1) has been implicated in cancer
      development. For example, knockdown of hNaa10 results in cancer cell death and
      the arrest of cell proliferation. It also sensitized cancer cells to drug-induced
      cytotoxicity. Human NatE has a distinct substrate specificity and is essential
      for normal chromosome segregation. Thus, NAT inhibitors may potentially be
      valuable anticancer therapeutics, either directly or as adjuvants. Herein, we
      report the design and synthesis of the first inhibitors targeting these enzymes.
      Using the substrate specificity of the enzymes as a guide, we synthesized three
      bisubstrate analogues that potently and selectively inhibit the NatA complex (CoA
      Ac-SES4; IC50 = 15.1 MUM), hNaa10, the catalytic subunit of NatA (CoA-Ac-EEE4; Ki
      = 1.6 MUM), and NatE/hNaa50 (CoA-Ac-MLG7; Ki* = 8 nM); CoA-Ac-EEE4 is a
      reversible competitive inhibitor of hNaa10, and CoA-Ac-MLG7 is a slow tight
      binding inhibitor of hNaa50. Our demonstration that it is possible to develop NAT
      selective inhibitors should assist future efforts to develop NAT inhibitors with
      more drug-like properties that can be used to chemically interrogate in vivo NAT
      function. 

PMID- 23557626
TI  - PTSD: past, present, and future.

PMID- 23557628
TI  - Dermo beta brachytherapy with 188-Re in squamous cell carcinoma of the penis: a
      new therapy.
AB  - BACKGROUND: Squamous cell carcinoma of the penis (SCCP) is the most common penis
      neoplasia, favoured by phimosis, HPV infection and scleroatrophic lichen. The
      classic therapy is surgical with anatomic demolition, which often causes
      important psychological problems. Other non-demolitive therapies can be utilized,
      such as radiotherapy, brachytherapy and topical medical treatment. OBJECTIVES: We
      propose a new non-invasive therapy called "Dermo beta brachytherapy (DBBT) with
      188-Re" in which a synthetic inert resin-matrix containing a radioactive beta
      emitting isotope is applied on the surface of the tumor lesion. MATERIALS AND
      METHODS: A total of 15 patients with a histologically confirmed diagnosis of SCCP
      were enrolled for treatment (DBBT). RESULTS: Of the 15 patients, 12 healed, 1 was
      lost at follow-up and 2 did not respond to therapy. CONCLUSION: The results
      indicate that DBBT is an effective treatment for SCC of the penis, sparing the
      anatomical integrity of the organ, and allowing normal sexual activity.

PMID- 23557627
TI  - The efficacy of initial hydrocortisone administration at preventing posttraumatic
      distress in adult trauma patients: a randomized trial.
AB  - OBJECTIVE/INTRODUCTION: Secondary pharmacological interventions have shown
      promise at reducing the development of posttraumatic stress disorder symptoms
      (PTSS) in preclinical studies. The present study examined the preliminary
      efficacy of a 10-day low-dose (20 mg bid) course of hydrocortisone at preventing
      PTSS in traumatic injury victims. METHODS: Sixty-four traumatic injury patients
      (34% female) were randomly assigned in a double-blind protocol to receive either
      a 10-day course of hydrocortisone or placebo initiated within 12 hours of the
      trauma. One-month and 3-months posttrauma participants completed an interview to
      assess PTSS and self-report measures of depression and health-related quality of
      life. RESULTS: Hydrocortisone recipients reported fewer PTSD and depression
      symptoms, and had greater improvements in health-related quality of life during
      the first 3 months posttrauma than did placebo recipients. Hydrocortisone
      recipients who had never received prior mental health treatment had the lowest
      PTSD scores. CONCLUSION: Low-dose hydrocortisone may be a promising approach to
      the prevention of PTSD in acutely injured trauma patients, and may be
      particularly efficacious in acutely injured trauma victims without a history of
      significant psychopathology.

PMID- 23557629
TI  - Resolution with rituximab of localized scleroderma occurring during etanercept
      treatment in a patient with rheumatoid arthritis.

PMID- 23557630
TI  - The high burden of cervical cancer in Fiji, 2004-07.
AB  - BACKGROUND: There are few population-based data on the disease burden of cervical
      cancer from developing countries, especially South Pacific islands. This study
      aimed to determine the incidence and mortality associated with cervical cancer
      and the coverage of Papanicolaou (Pap) cervical cytology in 20- to 69-year-old
      women in Fiji from 2004 to 2007. METHODS: National data on the incident cases of
      histologically confirmed cervical cancer and the associated deaths, and on Pap
      smear results were collected from all pathology laboratories, and cancer and
      death registries in Fiji from 2004 to 2007. RESULTS: There were 413 incident
      cases of cervical cancer and 215 related deaths during the study timeframe. The
      annualised incidence and mortality rates in 20- to 69-year-old Melanesian Fijian
      women, at 49.7 per 100?000 (95% confidence interval (CI): 43.7-56.4) and 32.3 per
      100?000 (95% CI: 26.9-38.4) respectively, were significantly higher than among 20
      to 69-year-old Indo-Fijian women at 35.2 per 100?000 (P<0.001, 95% CI: 29.5
      41.7) and 19.8 per 100?000 (P=0.002, 95% CI: 15.1-25.5) respectively. Of 330
      cases diagnosed between 2004 and 2006, 186 (56%) had died by 31 December 2006.
      Pap smear coverage for this period was 8.0% (95% CI: 7.9-8.1) of the target
      population. CONCLUSIONS: The incidence and mortality related to cervical cancer
      in Fiji is high, whereas Pap smear coverage is very low. Greater investment in
      alternative screening strategies and preventive measures should be integrated
      into a comprehensive, strategic cervical cancer control program in Fiji.

PMID- 23557631
TI  - The cDNA cloning of a novel bacterial blight-resistance gene ME137.

PMID- 23557632
TI  - Prion protein oligomer and its neurotoxicity.
AB  - The prion diseases, also known as transmissible spongiform encephalopathies, are
      fatal neurodegenerative disorders. According to the 'protein only' hypothesis,
      the key molecular event in the pathogenesis of prion disease is the
      conformational conversion of the host-derived cellular prion protein (PrP(C))
      into a misfolded form (scrapie PrP, PrP(Sc)). Increasing evidence has shown that
      the most infectious factor is the smaller subfibrillar oligomers formed by prion
      proteins. Both the prion oligomer and PrP(Sc) are rich in beta-sheet structure
      and resistant to the proteolysis of proteinase K. The prion oligomer is soluble
      in physiologic environments whereas PrP(Sc) is insoluble. Various prion oligomers
      are formed in different conditions. Prion oligomers exhibited more neurotoxicity
      both in vitro and in vivo than the fibrillar forms of PrP(Sc), implying that
      prion oligomers could be potential drug targets for attacking prion diseases. In
      this article, we describe recent experimental evidence regarding prion oligomers,
      with a special focus on prion oligomer formation and its neurotoxicity.

PMID- 23557633
TI  - Clinical complexity of Leishmania (Viannia) braziliensis infections amongst
      travelers.
AB  - The protozoan parasite Leishmania (Viannia) braziliensis is one of the main
      causes of cutaneous and mucocutaneous leishmaniasis in South America. Here, we
      describe three cases of L. (V.) braziliensis infection which were acquired during
      travelling in Bolivia, Peru or Paraguay and illustrate the phenotypic
      heterogeneity and therapeutic complexity of the disease. Two patients presented
      with unusual clinical manifestations, i.e. with prominent regional
      lymphadenopathy ("bubonic leishmaniasis") and with simultaneously emerged skin
      and mucosal lesions, respectively. Both patients insufficiently responded to oral
      treatment with miltefosine; resolution of the lesions was only achieved after a
      course of intravenous liposomal amphotericin B.

PMID- 23557634
TI  - Engaging non HIV specialist general practitioners with new priorities in HIV
      prevention and treatment: qualitative insights from those working in the field.
AB  - BACKGROUND: The science of HIV prevention and treatment is evolving rapidly,
      resulting in renewed calls to increase rates of HIV testing and, in particular,
      facilitate the timely and possibly earlier initiation of treatment, as this has
      the potential to dramatically reduce new infections. Little is known about how to
      engage non HIV specialist Australian general practitioners (GPs) with these new
      priorities. METHODS: Content related to the engagement of non HIV specialist GPs
      in the HIV response was identified within the transcripts of in-depth interviews
      with policy key informants (n=24) and general practice clinicians (n=47) engaged
      with HIV medicine. A qualitative analysis of the semantic meaning of this content
      identified three categories of 'issues' described by participants. RESULTS:
      Educational issues referred to a lack of attention to HIV in medical curricula, a
      perception that HIV care is only provided by HIV-specialist GPs, a need to make
      HIV testing more 'routine' in GP education and a need to strengthen GP awareness
      of referral options. Organisational issues encompassed time pressures in general
      practice, and a need for general practice nurses and for rapid testing to become
      available, as well as formalised peer mentoring and comanagement opportunities.
      Societal issues included the changing dynamics of HIV transmission and a need to
      reconnect GPs with the Australian HIV response. CONCLUSIONS: To successfully
      engage non HIV specialist GPs in the promotion of regular HIV testing and timely
      initiation of treatment, challenging issues affecting their capacity and
      willingness must be urgently addressed.

PMID- 23557635
TI  - Comment on the article "Auxiliary locking plate improves fracture stability and
      healing in intertrochanteric fractures fixated by intramedullary nail (IMN)" by
      Eberle et al.

PMID- 23557636
TI  - Nonenzymatic assembly of branched polyubiquitin chains for structural and
      biochemical studies.
AB  - Polymeric chains of a small protein ubiquitin are involved in regulation of
      nearly all vital processes in eukaryotic cells. Elucidating the signaling
      properties of polyubiquitin requires the ability to make these chains in vitro.
      In recent years, chemical and chemical-biology tools have been developed that
      produce fully natural isopeptide-linked polyUb chains with no need for linkage
      specific ubiquitin-conjugating enzymes. These methods produced unbranched chains
      (in which no more than one lysine per ubiquitin is conjugated to another
      ubiquitin). Here we report a nonenzymatic method for the assembly of fully
      natural isopeptide-linked branched polyubiquitin chains. This method is based on
      the use of mutually orthogonal removable protecting groups (e.g., Boc- and Alloc
      ) on lysines combined with an Ag-catalyzed condensation reaction between a C
      terminal thioester on one ubiquitin and a specific epsilon-amine on another
      ubiquitin, and involves genetic incorporation of more than one Lys(Boc) at the
      desired linkage positions in the ubiquitin sequence. We demonstrate our method by
      making a fully natural branched tri-ubiquitin containing isopeptide linkages via
      Lys11 and Lys33, and a (15)N-enriched proximal ubiquitin, which enabled monomer
      specific structural and dynamical studies by NMR. Furthermore, we assayed
      disassembly of branched and unbranched tri-ubiquitins as well as control di
      ubiquitins by the yeast proteasome-associated deubiquitinase Ubp6. Our results
      show that Ubp6 can recognize and disassemble a branched polyubiquitin, wherein
      cleavage preferences for individual linkages are retained. Our spectroscopic and
      functional data suggest that, at least for the chains studied here, the
      isopeptide linkages are effectively independent of each other. Together with our
      method for nonenzymatic assembly of unbranched polyubiquitin, these developments
      now provide tools for making fully natural polyubiquitin chains of essentially
      any type of linkage and length.

PMID- 23557637
TI  - Integrating weight bias awareness and mental health promotion into obesity
      prevention delivery: a public health pilot study.
AB  - INTRODUCTION: Promoting healthy weight is a top priority in Canada. Recent
      federal guidelines call for sustained, multisectoral partnerships that address
      childhood obesity on multiple levels. Current healthy weight messaging does not
      fully acknowledge the influence of social determinants of health on weight.
      METHODS: An interactive workshop was developed and implemented by a team of
      academic researchers and health promoters from the psychology and public health
      disciplines to raise awareness about 1) weight bias and its negative effect on
      health, 2) ways to balance healthy weight messaging to prevent the triggering of
      weight and shape preoccupation, and 3) the incorporation of mental health
      promotion into healthy weight messaging. We conducted a full-day workshop with
      342 Ontario public health promoters and administered a survey at preintervention,
      postintervention, and follow-up. RESULTS: Participation in the full-day workshop
      led to significant decreases in antifat attitudes and the internalization of
      media stereotypes and to significant increases in self-efficacy to address weight
      bias. Participants reported that the training heightened their awareness of their
      own personal weight biases and the need to broaden their scope of healthy weight
      promotion to include mental health promotion. There was consensus that additional
      sessions are warranted to help translate knowledge into action. Buy-in and
      resource support at the organizational level was also seen as pivotal.
      CONCLUSION: Professional development training in the area of weight bias
      awareness is associated with decreases in antifat attitudes and the
      internalization of media stereotypes around thinness. Health promoters' healthy
      weight messaging was improved by learning to avoid messages that trigger weight
      and shape preoccupation or unhealthful eating practices among children and youth.
      Participants also learned ways to integrate mental health promotion and
      resiliency-building into daily practice.

PMID- 23557638
TI  - Retailer adherence to Family Smoking Prevention and Tobacco Control Act, North
      Carolina, 2011.
AB  - INTRODUCTION: The Family Smoking Prevention and Tobacco Control Act regulates the
      sales and marketing of tobacco products in the United States; poor adherence by
      tobacco retailers may reduce the effectiveness of the Act's provisions. The
      objectives of this study were 1) to assess whether and to which provisions
      retailers were adherent and 2) to examine differences in adherence by county,
      retailer neighborhood, and retailer characteristics. METHODS: We conducted
      multivariate analysis of tobacco retailers' adherence to 12 point-of-sale
      provisions of the Tobacco Control Act in 3 North Carolina counties. We conducted
      observational audits of 324 retailers during 3 months in 2011 to assess
      adherence. We used logistic regression to assess associations between adherence
      to provisions and characteristics of each county, retailer neighborhood, and
      retailer. RESULTS: We found 15.7% of retailers did not adhere to at least 1
      provision; 84.3% adhered to all provisions. The provisions most frequently
      violated were the ban on sales of cigarettes with modified-risk labels (eg,
      "light" cigarettes) (43 [13.3%] retailers nonadherent) and the ban on self
      service for cigarettes and smokeless tobacco (6 [1.9%] retailers nonadherent). We
      found significant differences in rates of nonadherence by county and type of
      retailer. Pharmacies and drug stores were more than 3 times as likely as grocery
      stores to be nonadherent. CONCLUSION: Most tobacco retailers have implemented
      regulatory changes without enforcement by the US Food and Drug Administration.
      Monitoring rates of adherence by store type and locale (eg, county) may help
      retailers comply with point-of-sale provisions.

PMID- 23557639
TI  - Descriptive analysis of articles and advertisements pertaining to skin cancer
      prevention in 2 popular US parenting magazines, 2000-2010.
AB  - Magazines focused on parenting are popular in the United States, and parents may
      use them to guide decisions about the health of their children. We analyzed
      issues of 2 popular parenting magazines published in the past 11 years during the
      months of peak ultraviolet radiation exposure for content related to sun
      protection and for advertisements for skin products that did and did not contain
      sun protection factor. Only 24 of 2,594 articles addressed the topic of sun
      protection for skin cancer prevention. Although advertising is pervasive in these
      magazines, the extent to which such advertising focuses on products with sun
      protection factor was low. These findings suggest that parenting magazines can do
      more to assist parents in making informed decisions about preventing skin cancer
      risk among youth.

PMID- 23557640
TI  - Demand for weight loss counseling after copayment elimination.
AB  - INTRODUCTION: Overweight and obesity are public health issues in the United
      States, and veterans have a higher rate of overweight and obesity than the
      general population. Our objective was to examine whether copayment elimination
      increased use of a weight loss clinic by veterans. METHODS: We examined clinic
      use by 44,411 new patients seen in a Veterans Affairs (VA) MOVE! weight
      management clinic before the copayment elimination and clinic use by 64,398 new
      patients seen in the year after copayment elimination. We examined clinic use via
      mixed-effects models for patients who were already exempt from copayment and
      patients who were newly exempt from copayment. We used 2 outcomes before and
      after copayment elimination: 1) the ratio of number of clinic visits by new users
      with the mean number of MOVE! clinic visits by all users, and 2) the number of
      clinic visits by each new user in the 6 months after their first visit. All
      models were adjusted for patient and clinic factors. RESULTS: Among newly exempt
      patients, the clinic-standardized rate of new use increased by 2.2% after the
      copayment was eliminated but increased 12% among already exempt veterans. This
      finding was confirmed in adjusted analyses. Analysis of number of clinic visits
      adjusted for patient and clinic factors also found that exempt and nonexempt
      veterans had similar numbers of repeat clinic visits. CONCLUSION: We saw an
      unexpected larger increase in demand among veterans who receive all VA care for
      free. These results suggest that VA should not assume that copayment reductions
      for selective preventive services will motivate patient change and achieve
      intended system-level outcomes.

PMID- 23557641
TI  - [Family impact of FXTAS diagnosis: genetic counseling for at-risk relatives].
AB  - INTRODUCTION: Fragile X associated Tremor/Ataxia Syndrome (FXTAS) is related to
      premutation expansions of the FMR1 gene, including 55 to 200 CGG repeats, whereas
      full expansions, over 200 repeats, cause Fragile X mental retardation. FXTAS is
      observed in about one-third of men with premutation, generally in their 1950s and
      over, and less commonly in women. It is characterized by action tremor, ataxia,
      cognitive, parkinsonism, behavioral difficulties, autonomic dysfunction and
      peripheral neuropathy. Brain magnetic resonance imaging (MRI) often shows
      symmetric increases in T2-weighted signal intensity in the middle cerebellar
      peduncles. The diagnosis of FXTAS in a patient raises important family issues.
      CASE REPORT: A 47-year-old male patient complained of an abnormal hearing
      sensation and dizziness for several months. Neurological examination was normal.
      Brain MRI showed the common signal intensity in middle cerebellar peduncles and
      bilateral punctual increases in T2-weighted signal intensity in the cerebral
      white matter. Genetic analysis showed 87CGG repeats, in favor of a possible
      FXTAS. At the time of diagnosis, fragile X syndrome was subsequently suspected
      and confirmed in his 10-month-old grandson. DISCUSSION: Due to X-linked
      inheritance and to the specific related mutational mechanism, the diagnosis of
      FXTAS in a patient raises major issues for relatives over several generations,
      including males and females, who should be considered as obligate or potential
      premutation carriers. Premutated females are not only at risk of transmitting a
      full mutation to their children but also of developing Fragile X related
      premature ovarian failure (FXPOI) that may influence their choices in family
      planning. CONCLUSION: The diagnosis of FXATS in a patient should induce delivery
      of extensive information and genetic counseling for potential carrier relatives.

PMID- 23557642
TI  - Priming ammonia lyases and aminomutases for industrial and therapeutic
      applications.
AB  - Ammonia lyases (AL) and aminomutases (AM) are emerging in green synthetic routes
      to chiral amines and an AL is being explored as an enzyme therapeutic for
      treating phenylketonuria and cancer. Although the restricted substrate range of
      the wild-type enzymes limits their widespread application, the non-reliance on
      external cofactors and direct functionalization of an olefinic bond make ammonia
      lyases attractive biocatalysts for use in the synthesis of natural and non
      natural amino acids, including beta-amino acids. The approach of combining
      structure-guided enzyme engineering with efficient mutant library screening has
      extended the synthetic scope of these enzymes in recent years and has resolved
      important mechanistic issues for AMs and ALs, including those containing the MIO
      (4-methylideneimidazole-5-one) internal cofactor.

PMID- 23557643
TI  - The role of ghrelin in energy balance regulation in fish.
AB  - Knowledge about the endocrine regulation of energy balance in fish is of interest
      for basic as well as aquaculture research. Ghrelin is a peptide hormone that was
      first identified in fish 10 years ago and has important roles in the control of
      food intake and metabolism. Both ghrelin and its receptor, the growth hormone
      secretagogue receptor (GHS-R), have been found in numerous fish species. Their
      tissue distributions support the idea that ghrelin has an integrative role in the
      regulation of energy balance at both the central nervous system level and
      systemic level. In tilapia and goldfish, ghrelin treatment appears to increase
      food intake and to stimulate lipogenesis and tissue fat deposition to promote a
      more positive energy status. In rainbow trout, on the other hand, ghrelin
      decreases food intake. Goldfish and rainbow trout are the fish species in which
      the mode of action of ghrelin on food intake has been most thoroughly
      investigated. The results from these studies indicate that ghrelin alters food
      intake by acting on well-known appetite signals, such as CRH, NPY and orexin, in
      the hypothalamus in a species-specific manner. In goldfish, sensory fibres of the
      vagus nerve convey the signal from gut-derived ghrelin to modulate appetite. The
      data also indicate that ghrelin may modulate foraging/swimming activity and the
      perception of food in fish. Results related to the effects of energy status,
      temperature, and stressors on plasma ghrelin/tissue ghrelin mRNA levels are
      occasionally inconsistent between short- and long-term studies, between the
      protein and mRNA, and between species. Recent data also imply a role of ghrelin
      in carbohydrate metabolism. More functional studies are required to understand
      the role of ghrelin and its mechanisms of action in the regulation of energy
      balance among fish.

PMID- 23557644
TI  - Daily rhythms of urotensin I and II gene expression and hormone secretion in the
      caudal neurosecretory system of the euryhaline flounder (Platichthys flesus).
AB  - The caudal neurosecretory system (CNSS) is a unique neuroendocrine structure for
      environmental adaptation in fish, and is the major site of expression and
      secretion of urotensin I (UI) and II (UII). This study examined daily changes in
      mRNA expression and the secretion profile of UI and UII in the CNSS. Daily
      rhythms were observed in mRNA level of CNSS UI, urophysis UI, plasma UII,
      glucose, potassium and sodium. No statistically significant (Cosinor, P>0.05)
      diel rhythmicity in mRNA level of CNSS UII, urophysis UII, cortisol, lactate,
      osmolality and chloride were detected. The calculated acrophase of sodium,
      cortisol, plasma UII, urophysis UII, urophysis UI and mRNA level of CNSS UI
      rhythms were recorded at 13:04 h, 13:39 h, 14:45 h, 15:27 h, 14:41 h and 14:39 h,
      respectively and a positive relationship was evident among them. The acrophase of
      glucose and potassium rhythms were recorded at 18:57 h and 22:35 h, respectively.
      The glucose levels increased progressively at the onset of the UII surge at 15:00
      h and reached peak values at dusk. The results support the hypothesis that the
      CNSS may play a role in the control of co-ordinated daily changes in energy
      mobilization, nutritional behavior and osmoregulatory systems in euryhaline
      flounder. Our findings described for the first time the existence of daily
      rhythms of CNSS hormone expression and secretion in Platichthys flesus. These
      results reveal the importance of taking into account the time of day when
      assessing stress responses and evaluating UI and UII as physiological indicators
      of stress in this species.

PMID- 23557645
TI  - Signaling by Drosophila capa neuropeptides.
AB  - The capa peptide family, originally identified in the tobacco hawk moth, Manduca
      sexta, is now known to be present in many insect families, with increasing
      publications on capa neuropeptides each year. The physiological actions of capa
      peptides vary depending on the insect species but capa peptides have key
      myomodulatory and osmoregulatory functions, depending on insect lifestyle, and
      life stage. Capa peptide signaling is thus critical for fluid homeostasis and
      survival, making study of this neuropeptide family attractive for novel routes
      for insect control. In Dipteran species, including the genetically tractable
      Drosophila melanogaster, capa peptide action is diuretic; via elevation of nitric
      oxide, cGMP and calcium in the principal cells of the Malpighian tubules. The
      identification of the capa receptor (capaR) in several insect species has shown
      this to be a canonical GPCR. In D. melanogaster, ligand-activated capaR activity
      occurs in a dose-dependent manner between 10(-6) and 10(-12)M. Lower
      concentrations of capa peptide do not activate capaR, either in adult or larval
      Malpighian tubules. Use of transgenic flies in which capaR is knocked-down in
      only Malpighian tubule principal cells demonstrates that capaR modulates tubule
      fluid secretion rates and in doing so, sets the organismal response to
      desiccation. Thus, capa regulates a desiccation-responsive pathway in D.
      melanogaster, linking its role in osmoregulation and fluid homeostasis to
      environmental response and survival. The conservation of capa action between some
      Dipteran species suggests that capa's role in desiccation tolerance may not be
      confined to D. melanogaster.

PMID- 23557646
TI  - MEK1/2 differentially participates in GnRH actions on goldfish LH and GH
      secretion and hormone protein availability: acute and long-term effects, in
      vitro.
AB  - Two endogenous gonadotropin-releasing hormones (GnRHs), sGnRH and cGnRH-II,
      stimulate LH and GH release via protein kinase C (PKC) signaling in goldfish. In
      this study, extracellular signal-regulated kinase kinase 1 and 2 (MEK1/2)
      involvement in acute and prolonged GnRH effects on goldfish gonadotrope and
      somatotrope functions, as well as potential interactions with PKC in the control
      of LH and GH release from goldfish pituitary cells was investigated. MEK1/2
      inhibitors U0126 and PD098059 significantly decreased sGnRH but not cGnRH-II
      stimulated GH release from perifused goldfish pituitary cells and U0126
      significantly reduced the GH, but not the LH, release responses to synthetic PKC
      activators. In long-term static incubations (up to 24h) with goldfish pituitary
      cells, U0126 generally did not affect basal LH release but attenuated sGnRH- and
      cGnRH-II-induced LH release, as well as the time-dependent effects of sGnRH
      and/or cGnRH-II to elevate total LH availability (sum of release and cell
      content). sGnRH and cGnRH-II reduced cellular GH content and/or total GH
      availability at 2, 6, and 12h while static incubation with U0126 alone generally
      increased basal GH release but reduced cellular GH content and/or the total
      amount of GH available. U0126 also selectively reduced the sGnRH-induced GH
      release responses at 6 and 24h but paradoxically inhibited cGnRH-II-stimulated GH
      secretion while enhancing sGnRH-elicited GH release at 2h. Taken together, this
      study reveals the complexity of GnRH-stimulated MEK1/2 signaling and adds to our
      understanding of cell-type- and GnRH-isoform-selective signal transduction in the
      regulation of pituitary cell hormone release and production. 

PMID- 23557647
TI  - Cutaneous metastasis of gastric adenocarcinoma presenting as carcinoma "en
      cuirasse".

PMID- 23557649
TI  - The origins of the condom.

PMID- 23557648
TI  - Persulfide reactivity in the detection of protein s-sulfhydration.
AB  - Hydrogen sulfide (H2S) has emerged as a new member of the gaseous transmitter
      family of signaling molecules and appears to play a regulatory role in the
      cardiovascular and nervous systems. Recent studies suggest that protein cysteine
      S-sulfhydration may function as a mechanism for transforming the H2S signal into
      a biological response. However, selective detection of S-sulfhydryl modifications
      is challenging since the persulfide group (RSSH) exhibits reactivity akin to
      other sulfur species, especially thiols. A modification of the biotin switch
      technique, using S-methyl methanethiosulfonate (MMTS) as an alkylating reagent,
      was recently used to identify a large number of proteins that may undergo S
      sulfhydration, but the underlying mechanism of chemical detection was not fully
      explored. To address this key issue, we have developed a protein persulfide model
      and analogue of MMTS, S-4-bromobenzyl methanethiosulfonate (BBMTS). Using these
      new reagents, we investigated the chemistry in the modified biotin switch method
      and examined the reactivity of protein persulfides toward different
      electrophile/nucleophile species. Together, our data affirm the nucleophilic
      properties of the persulfide sulfane sulfur and afford new insights into protein
      S-sulfhydryl chemistry, which may be exploited in future detection strategies. 

PMID- 23557650
TI  - Quality of life in pediatric dermatology.
AB  - Skin disease is highly prevalent in the United States, and it has been well
      documented that patients with skin disease experience financial, psychological,
      social, and quality-of-life (QoL) burdens beyond those of the general population.
      Pediatric patients and their caregivers are particularly vulnerable to the burden
      of skin disease. Over the past decade disease-specific indices for QoL
      measurement in pediatric dermatology have been developed. Most of this research
      has focused on acne, atopic dermatitis, hemangiomas, ichythosis, psoriasis, and
      vitiligo. This article provides an overview of QoL assessment in pediatric
      dermatology for these six conditions.

PMID- 23557651
TI  - The child with recalcitrant dermatitis: when to worry?
AB  - Dermatitis is a frequent cause for referral to the pediatric dermatologist. In
      this article, a brief overview is given of common childhood dermatoses as well as
      some rarer dermatoses that may give the clinician cause for concern. Widespread
      scaling and erythema, described as erythroderma, are a cause of frustration for
      patients, families, and their physician(s). Both unusual and common skin
      disorders can present in this fashion. Just as recognizing common dermatoses is
      important, it is also important to recognize when a dermatitis fails to fit the
      common pattern and may prompt further investigation.

PMID- 23557652
TI  - Pediatric morphea.
AB  - This article outlines the epidemiology, pathogenesis, clinical presentation,
      diagnosis, and treatment of childhood morphea. Also known as localized
      scleroderma, morphea is a fibrosing disorder of the skin and subcutaneous
      tissues. Morphea is differentiated from systemic sclerosis (scleroderma) based on
      the absence of sclerodactyly, Raynaud phenomenon, and nail-fold capillary
      changes. Confusion may occur because patients with morphea often have systemic
      symptoms such as malaise, fatigue, arthralgias, myalgias, and positive
      autoantibodies. Unlike morphea, systemic sclerosis has organ involvement,
      particularly gastrointestinal, pulmonary, and renal.

PMID- 23557653
TI  - Common pediatric skin conditions with protracted courses: a therapeutic update.
AB  - This article reviews some of the recent literature on therapeutic modalities and
      their efficacy in common pediatric skin conditions. Immunotherapy and laser
      therapy of warts and molluscum contagiosum show therapeutic promise. Bleach baths
      may help in eradicating Staphylococcus aureus carriage and in improving atopic
      dermatitis. Cephalexin continues to show efficacy even with increased incidence
      of community-acquired methicillin-resistant Staphylococcus aureus. More studies
      have looked at the use of systemic immunosuppressants for alopecia areata and
      vitiligo in children, although risks and benefits of therapy must be weighed. The
      excimer laser shows promise as a treatment modality for both alopecia areata and
      vitiligo.

PMID- 23557654
TI  - Imaging of vascular anomalies.
AB  - Accurate characterization of vascular anomalies is important in predicting
      clinical course and guiding treatment. This article provides an imaging review of
      vascular anomalies, highlighting the particular imaging characteristics of
      hemangiomas and malformations. Discussed are the appropriate imaging modalities
      for the evaluation of the anomalies and the associated abnormalities that require
      further investigation.

PMID- 23557655
TI  - Systemic treatments for severe pediatric psoriasis: a practical approach.
AB  - Severe psoriasis is uncommon in children, but when it occurs, can be physically,
      emotionally and socially disabling. Systemic treatments such as phototherapy,
      acitretin, methotrexate and cyclosporine have been used to manage severe
      pediatric psoriasis for decades. Newer biologic agents have demonstrated their
      effectiveness in adult psoriasis and are accumulating promising data in children.
      This article discusses the use of these treatments including their indications,
      efficacy, adverse effects, and monitoring requirements. The aim is to provide
      practical, clinically relevant information regarding the use of these medications
      alone and in various combinations based on available evidence and cumulative
      experience.

PMID- 23557656
TI  - Approach to the patient with an infantile hemangioma.
AB  - Infantile hemangioma is the most common soft tissue tumor of childhood. Despite
      its frequency, it has only been in the last decade that these lesions have been
      better characterized and become the subject of significant clinical and
      translational research. Although most infantile hemangiomas are uncomplicated and
      do not require intervention, they can be a significant source of parental
      distress, cosmetic disfigurement, and morbidity. The wide spectrum of disease in
      the morphology of these lesions and in their behavior has made it difficult to
      predict the need for treatment and has made it challenging to establish a
      standardized approach to management.

PMID- 23557657
TI  - New findings in genodermatoses.
AB  - New technologies are accelerating the pace at which genetic defects leading to
      inherited skin disease are elucidated. Translation of these genetic discoveries
      into new therapies for patients with inherited skin diseases has not been as
      rapid but the pace is now accelerating. This article summarizes recent findings
      in genetic skin diseases, the scope of advances being made, the role of new DNA
      analysis technologies in these discoveries, as well as highlighting some examples
      of how an understanding of the genetic cause of inherited skin diseases can lead
      to therapeutic interventions for patients.

PMID- 23557658
TI  - Pediatric photosensitivity disorders.
AB  - Photosensitivity disorders in childhood are rare, with the notable exception of
      overexposure as sunburn, and therefore require a more circumspect approach.
      Practitioners who treat children are key players in identifying and managing the
      many photosensitivity disorders that rarely present in childhood. A classic
      photodistribution of skin findings may suggest photosensitivity, but a correct
      diagnosis depends on a detailed history correlated with clinical findings.

PMID- 23557659
TI  - Spitz nevi: a bridge between dermoscopic morphology and histopathology.
AB  - Few benign melanocytic lesions encountered in clinical practice elicit the level
      of controversy as that generated by lesions within the spectrum of Spitz nevi.
      Unlike melanoma, the dermoscopic structures found in Spitz nevi tend to be
      distributed in a symmetric and organized manner. This review highlights the
      melanoma-specific structures and patterns commonly seen in Spitz nevi. Knowledge
      of the dermoscopic structures and patterns encountered in Spitz nevi
      (particularly the classic symmetric starburst pattern), together with
      understanding of their growth dynamics, can inform the decision whether to biopsy
      or monitor.

PMID- 23557660
TI  - Procedural pediatric dermatology.
AB  - Due to many factors, including parental anxiety, a child's inability to
      understand the necessity of a procedure and a child's unwillingness to cooperate,
      it can be much more challenging to perform dermatologic procedures in children.
      This article reviews pre-procedural preparation of patients and parents,
      techniques for minimizing injection-related pain and optimal timing of surgical
      intervention. The risks and benefits of general anesthesia in the setting of
      pediatric dermatologic procedures are discussed. Additionally, the surgical
      approach to a few specific types of birthmarks is addressed.

PMID- 23557661
TI  - The role of psychiatry and psychology collaboration in pediatric dermatology.
AB  - Psychiatric issues inherently accompany dermatologic disease in children and
      adolescents. With body image issues being of paramount importance to adolescents,
      perceived flaws may be accompanied by depression, anxiety, or loss of usual
      functioning. Children and adolescents also often have difficulties with treatment
      compliance. Often medical professionals separate symptoms into physical versus
      psychosomatic. This differentiation is not a useful dichotomy, and interventions
      should be aimed at both physical and emotional needs simultaneously. A
      collaborative team approach with both dermatologist and psychiatrist/psychologist
      addressing physical and emotional symptoms is therefore favored for desirable
      results.

PMID- 23557663
TI  - Postoperative imaging after lung transplantation.
AB  - Lung transplantation (LT) is an established procedure for chronic end-stage lung
      diseases. Complications are frequent and diverse and are the consequence of the
      complex surgical technique, the severity of the initial pathology, and the deep
      state of posttransplantation immunosuppression. Complications following LT
      include primary graft dysfunction, rejection (hyperacute, acute, and chronic),
      infections, posttransplantation lymphoproliferative disease, pleural and airway
      complications, native lung complications, and recurrence of primary disease. An
      understanding of these complications, their temporal evolution, and the role of
      radiology and other diagnostic methods in their diagnosis and management will
      help reduce the morbidity and mortality associated with LT.

PMID- 23557664
TI  - Matched molecular pair analysis in drug discovery.
AB  - Multiple parameter optimisation in drug discovery is difficult, but Matched
      Molecular Pair Analysis (MMPA) can help. Computer algorithms can process data in
      an unbiased way to yield design rules and suggest better molecules, cutting the
      number of design cycles. The approach often makes more suggestions than can be
      processed manually and methods to deal with this are proposed. However, there is
      a paucity of contextually specific design rules, which would truly make the
      technique powerful. By combining extracted information from multiple sources
      there is an opportunity to solve this problem and advance medicinal chemistry in
      a matter of months rather than years. 

PMID- 23557665
TI  - Baculovirus expression and diagnostic utility of the glycoprotein E of bovine
      herpesvirus-1.1 Egyptian strain "Abu-Hammad".
AB  - A recombinant baculovirus construct expressing glycoprotein E (gE) of the
      Egyptian BoHV-1.1 Abu-Hammad strain (rBac/gE-AbuH) was generated and
      characterized. The recombinant gE (rgE) secreting protein in culture medium of
      infected insect cells was used as a coating antigen in an indirect enzyme-linked
      immunosorbent assay (ELISA) to test its utility for detection of antibody against
      gE of BoHV-1. Indirect gE-ELISA was compared to standard virus neutralization
      test and commercial blocking gE-ELISA for detection of anti-gE antibody in a
      panel of bovine sera. Antibody titers estimated by both ELISAs were closely
      correlated with those determined by virus neutralization test. In conclusion, the
      developed indirect gE-ELISA was a reliable candidate for inexpensive detection of
      anti-gE antibody in control and experimental bovine sera with high specificity
      and sensitivity. Moreover, it emphasized the diagnostic utility of gE based
      ELISAs to distinguish cattle infected with BoHV-1 from those vaccinated with the
      gE negative mutants.

PMID- 23557666
TI  - Development of a virus concentration method using lanthanum-based chemical
      flocculation coupled with modified membrane filtration procedures.
AB  - Direct membrane filtration is often used to concentrate viruses in water but it
      may suffer from severe membrane fouling and clogging. Here, a lanthanum-based
      flocculation method coupled with modified membrane filtration procedures was
      developed and evaluated to detect viruses in large volume (40 L) water samples.
      The lanthanum-based flocculation method could easily reduce the water sample
      volume by a factor of 40. Additional volume reduction was achieved by a two-step
      membrane filtration approach. First, selected membrane filters (including 1MDS
      electropositive filters and nitrocellulose electronegative filters-Millipore HATF
      filters) were used to reduce water sample volume further and compare their
      efficiencies in virus recovery. The Mg2+-modified HATF membrane performed better
      on MS2 retention with an average virus recovery of 83.4% (+/-4.5% [standard
      deviation]). After HATF membrane filtration and elution, centrifugal
      ultrafiltration through a 30 kDa cut-off membrane resulted in an overall
      concentration factor of 20,000. Results from the infectivity assay showed that
      the MS2 recovery efficiencies from the NanoCeram- and 1MDS-based direct
      filtration and the lanthanum-based concentration coupled with the modified
      filtration procedure were 10.1% (+/-1.0%), 3.3% (+/-0.1%), and 17.5% (+/-1.1%),
      respectively. Results from the PCR analysis showed that the virus recoveries of
      the lanthanum-based method were 20.6% (+/-2.9%) and 19.5% (+/-3.4%) for MS2 and
      adenovirus, respectively, while no adenovirus could be detected through the
      NanoCeram- and 1MDS-based direct filtration. The lanthanum-based concentration
      method coupled with modified membrane filtration procedures is therefore a
      promising method for detecting waterborne viruses.

PMID- 23557667
TI  - Development of a gold nanoparticle-based oligonucleotide microarray for
      simultaneous detection of seven swine viruses.
AB  - A gold nanoparticle (GNP) based oligonucleotide microarray assay (GNMA) that
      combined GNP-based multiplex asymmetric PCR with silver enhancement detection,
      was developed for simultaneous detection of seven important swine viruses in
      intensive swine production. Multiplex PCR was first performed to enable the
      target fragments of seven viruses containing a universal sequence, which were
      labeled simultaneously with GNPs by multiplex asymmetric PCR in the presence of
      excess GNP-conjugated primer. Target labeled products were captured by virus
      specific oligonucleotide probes immobilized on microarrays, followed by silver
      staining for signal enhancement. Black image of microarray spots was easily
      detected by the naked eye or a simple flatbed scanner and quantified. The results
      for purified plasmid constructs indicated that the assay was highly specific for
      detecting the seven viruses in single or multiple infections, and as few as 6-80
      copies/MUl of specific viral target fragments were detected successfully. Fifty
      seven archived samples were tested by this assay, and the results were 100%
      consistent with previous results based on real-time PCR and those obtained by
      conventional PCR/RT-PCR and sequencing. The assay is appropriate for the routine
      diagnosis of viral infections in pigs due to its simplicity, low-cost, high
      specificity and sensitivity.

PMID- 23557668
TI  - A novel indirect immunofluorescence test for the detection of IgG and IgA
      antibodies for diagnosis of Hepatitis E Virus infections.
AB  - Hepatitis E Virus (HEV) causes epidemic infections in regions of poor hygiene in
      the developing world. Over the last years, however, increasing numbers of
      autochthonous infections in industrialized countries have been described, leading
      to new interest in this pathogen. Currently available serological test formats to
      detect IgG and IgM antibodies are mainly based on bacterially expressed ORF2 and
      ORF3 antigens and often give ambiguous results. The objective of this study was
      the development of a different assay format for HEV diagnosis--a HEV
      immunofluorescence test (HEV-IFT) based on mammalian cells transiently expressing
      recombinant HEV ORF2 protein with a simple production and staining protocol and
      the investigation of its performance and methodical feasibility under diagnostic
      laboratory conditions. 31 sera of patients at different phases of HEV infection
      and 40 control sera from a non-endemic region were analyzed for anti-HEV IgG,
      IgM, and IgA antibodies. The HEV-IFT detected successfully anti-HEV IgG and IgA,
      but not anti-HEV IgM antibodies. In the study group the HEV-IFT was able to
      confirm HEV infections and to support diagnosis when ambiguous results were
      obtained by commercial assays. Signal localization and staining patterns helped
      to gather additional information about reactive antibodies present in patient
      sera. In conclusion the developed IFT for the detection of anti-HEV IgG and IgA
      antibodies can be used for diagnosis and for the serological confirmation of HEV
      infections.

PMID- 23557669
TI  - Evaluation of a non-invasive, inhalational challenge method for rabies vaccine
      potency assay.
AB  - Veterinary rabies vaccines are essential for safeguarding the public from
      exposure to rabies virus, as vaccination of domestic animals provides a barrier
      between humans and wildlife reservoirs. Ensuring rabies vaccines are potent and
      effective is paramount in preventing human exposure to rabies virus. The National
      Institutes of Health (NIH) test, a mouse vaccination-challenge assay, is the most
      widely used and internationally recognized assay for potency testing of
      inactivated rabies vaccines, and it is currently considered the method of choice.
      In the NIH test, vaccinated mice are challenged by the intracranial (IC) route.
      The response to the IC challenge can be variable, which often results in invalid
      tests. In addition, the IC challenge-exposure raises animal welfare concerns. The
      objective of this study was to evaluate the intranasal route of challenge as a
      modification to the NIH test to reduce animal pain and suffering until harmonized
      requirements for in vitro testing of rabies vaccines are developed. Results
      confirm the intranasal route is an effective route of rabies challenge in mice.
      However, a valid challenge requires the use of a more concentrated inoculum, in
      comparison to the intracranial method.

PMID- 23557670
TI  - Development and application of a universal Taqman real-time PCR for quantitation
      of duck hepatitis B virus DNA.
AB  - To develop a quantitative assay for universal detection of duck hepatitis B virus
      (DHBV) DNA, a Taqman real-time fluorescent quantitative polymerase chain reaction
      (FQ-PCR) assay was developed using primers and probes based on genomic sequences
      located at nucleotide 241-414 of the DHBV Core region which possesses the highest
      homology among the 44 DHBV genomes available in Genbank. The DHBV Core gene
      cloned in pGEM-T was used to generate DHBV DNA standard. The assay had a lowest
      detection limit of 10(3) copies/ml and a good linear standard curve (Y=
      3.989X+49.086, r(2)=0.9993) over a wide range of input DHBV DNA (10(3) to 10(10)
      copies/ml). The standard deviation of intra- and inter-assay was 0.01-0.06 and
      0.05-0.16, respectively, and the coefficient of variation was 1.3-1.8%. The
      specificity of the assay was validated using duck hepatitis virus type 1,
      hepatitis B virus, and E. coli DNA. Comparison of ABI 7300 and Bio-Rad iQ5 PCR
      instruments yielded highly consistent results. The assay showed a positive rate
      of 63.8% (51/80) DHBV DNA in peripheral blood and liver tissue from ducks from
      Xi'an, China. The FQ-PCR developed is highly sensitive, specific, reproducible
      and versatile, and may be used to universally detect DHBV DNA of different DHBV
      strains.

PMID- 23557671
TI  - Updating beliefs and combining evidence in adaptive forest management under
      climate change: a case study of Norway spruce (Picea abies L. Karst) in the Black
      Forest, Germany.
AB  - We study climate uncertainty and how managers' beliefs about climate change
      develop and influence their decisions. We develop an approach for updating
      knowledge and beliefs based on the observation of forest and climate variables
      and illustrate its application for the adaptive management of an even-aged Norway
      spruce (Picea abies L. Karst) forest in the Black Forest, Germany. We simulated
      forest development under a range of climate change scenarios and forest
      management alternatives. Our analysis used Bayesian updating and Dempster's rule
      of combination to simulate how observations of climate and forest variables may
      influence a decision maker's beliefs about climate development and thereby
      management decisions. While forest managers may be inclined to rely on observed
      forest variables to infer climate change and impacts, we found that observation
      of climate state, e.g. temperature or precipitation is superior for updating
      beliefs and supporting decision-making. However, with little conflict among
      information sources, the strongest evidence would be offered by a combination of
      at least two informative variables, e.g., temperature and precipitation. The
      success of adaptive forest management depends on when managers switch to forward
      looking management schemes. Thus, robust climate adaptation policies may depend
      crucially on a better understanding of what factors influence managers' belief in
      climate change.

PMID- 23557672
TI  - Next-generation sequencing reveals genomic features in the Japanese quail.
AB  - The Japanese quail has several advantages as a laboratory animal for biological
      and biomedical investigations. In this study, the draft genome of the Japanese
      quail was sequenced and assembled using next-generation sequencing technology. To
      improve the quality of the assembly, the sequence reads from the Japanese quail
      were aligned against the reference genome of the chicken. The final draft
      assembly consisted of 1.75 Gbp with an N50 contig length of 11,409 bp. On the
      basis of the draft genome sequence obtained, we developed 100 microsatellite
      markers and used these markers to evaluate the genetic variability and diversity
      of 11 lines of Japanese quail. Furthermore, we identified Japanese quail
      orthologs of spermatogenesis markers and analyzed their expression using in situ
      hybridization. The Japanese quail genome sequence obtained in the present study
      could enhance the value of this species as a model animal.

PMID- 23557673
TI  - Toxicity assessment of Chlorella vulgaris and Chlorella protothecoides following
      exposure to Pb(II).
AB  - The short- and long-term toxic effects of Pb(II) exposure on Chlorella vulgaris
      (C. vulgaris) and Chlorella protothecoides (C. protothecoides) were not well
      understood. The lab study was performed to observe the Pb(II) exposure induced
      changes. Results of the observations show: (1) higher level of Pb(II) (50 or
      80mgL(-1)) could significantly inhibit the growth and chlorophyll a synthesis of
      both algae in almost all the treatments and dose-response relationships could be
      clearly observed, (2) the range of EC50 values (24-120h, 67.73-172.45mgL(-1))
      indicated that Pb(II) had a relatively limited short-term toxicity to the two
      algae, while long-term tests (7-28d, 50.41-63.91mgL(-1)) displayed higher
      toxicity and (3) SOD and CAT activities of both algae after exposed to medium
      level of Pb(II) were significantly promoted, and their response might be more
      susceptible in short-term exposure. This research provides a basic understanding
      of Pb(II) toxicity to aquatic organisms.

PMID- 23557674
TI  - [Clozapine rechallenge in resistant schizophrenia disorder affecting "super
      sensitive" patients, after neutropenia under clozapine: a case report].
AB  - INTRODUCTION AND OBJECTIVE: The frequency of agranulocytosis induced by
      psychoactive drugs is estimated the first year of around 0.8% under clozapine,
      against 0.13% under chlorpromazine (King and Wager, 1998 [3]). It is associated
      with a mortality rate of 5 to 10%, and requires heavy treatment, usually in an
      intensive care unit. The objective of this paper is to present a practical
      therapeutic answer (clozapine rechallenge with filgrastim) through a case report
      following a neutropenia episode preventing clozapine use. CASE AND METHODS: B.N.
      aged 35, native of Martinique, shows a resistant schizophrenia disorder "ultra
      sensitive" to clozapine. Without any treatment, after 4 years in stable clinical
      state under clozapine, B.N. suffered three neutropenia episodes when absorbing
      clozapine (2008, 2010 and 2011). First, a literature survey was conducted along
      with a consultation of the head of pharmacovigilance regional center and the
      hematology referee. Then, a 4th clozapine treatment was decided under cover of
      filgrastim (G-CSF), the role of which is to limit the risk of a new neutropenia.
      After stopping all psychoactive drugs, except morphine, the subject benefited
      from a first 0.3mg filgrastim injection, the day before re-introducing 25mg
      clozapine. Before treatment: Leucocytes=4.8 G/L while absolute neutrophils
      count=2.4 G/L. Filgrastim injections were carried out at a rate of two 0.3mg
      injections per week. Clozapine was increased to reach 25mg every 3 days and
      electroconvulsivotherapy continued fortnightly while supervision was double: on
      the first hand, daily and clinical search for an increase in body temperature and
      signs of treatment intolerance, and on the other hand biological surveillance
      with NFS three times a week besides weekly clozapinemia. The well-informed
      consent of the patient was obtained. RESULTS: Signs of improvement were noticed
      as early as the 8th day and after 8 weeks of treatment and 31 sessions of ECT,
      the patient was stabilized under clozapine at 300 mg per day. The evolution is
      clearly favorable, as PANNS evolved from 158 to 90. Neutropenia episodes were not
      observed with a lowest measured rate of 1.9 G/L neutrophils. The filgrastim
      dosage was then reduced to 0.3mg per week from the 7th week onwards, along with
      the pursuit of a weekly NFS supervision throughout the treatment. Tolerance is
      satisfying, with an improvement in lipid check, glycaemia, blood pressure and QT
      intervals during ECG. DISCUSSION AND CONCLUSION: The B.N. case isn't an isolated
      one as several articles refer to filgrastim use, combined with clozapine. This
      confirms the role of hematopoietic cytokines (mainly G-CSF) in neutropenia
      episodes induced by clozapine. Filgrastim dosage appears to be an important point
      with regards to the risk of a new neutropenia episode. Let's mention also that it
      is not a harmless treatment, it could hide the occurrence of neutropenia, besides
      it's expensive and invasive. Clinical and biological supervision is essential as
      the probability of an enhanced malignant hemopathy is low but nonetheless
      present. We also noticed a "biased notoriety of the clozapine", with the
      association with other hematotoxic molecules, the existence of a circadian rhythm
      of neutrophils or G-CSF, along with transitional or ethnical neutropenia. These
      points should be discussed thoroughly before exclusively accusing clozapine; this
      in turn would have consequences regarding the possibility of treatment
      resumption. Finally, association with lithium is also an option; several cases
      have already been reported.

PMID- 23557675
TI  - Prenatal famine and adult mental illness: interpreting concordant and discordant
      results from the Dutch and Chinese Famines.

PMID- 23557676
TI  - Tritium analysis of urine samples from the general Korean public.
AB  - The tritium concentrations of urine samples and the effective dose of the general
      Korean public were evaluated. To achieve accurate HTO analysis of urine samples,
      we established the optimal conditions for measuring the HTO content of urine
      samples. Urine samples from 50 Koreans who do not work at a nuclear facility were
      analyzed on the basis of the results. The average urine analysis result was 2.8
      +/-1 .4 Bq/L, and the range was 1.8-5.6 Bq/L. The measured values were lower than
      those reported for other countries. These results show that environmental factors
      and lifestyle differences are the main factors affecting the tritium level of the
      general public.

PMID- 23557677
TI  - Mammalian neuronal sodium channel blocker MU-conotoxin BuIIIB has a structured N
      terminus that influences potency.
AB  - Among the MU-conotoxins that block vertebrate voltage-gated sodium channels
      (VGSCs), some have been shown to be potent analgesics following systemic
      administration in mice. We have determined the solution structure of a new
      representative of this family, MU-BuIIIB, and established its disulfide
      connectivities by direct mass spectrometric collision induced dissociation
      fragmentation of the peptide with disulfides intact. The major oxidative folding
      product adopts a 1-4/2-5/3-6 pattern with the following disulfide bridges: Cys5
      Cys17, Cys6-Cys23, and Cys13-Cys24. The solution structure reveals that the
      unique N-terminal extension in MU-BuIIIB, which is also present in MU-BuIIIA and
      MU-BuIIIC but absent in other MU-conotoxins, forms part of a short alpha-helix
      encompassing Glu3 to Asn8. This helix is packed against the rest of the toxin and
      stabilized by the Cys5-Cys17 and Cys6-Cys23 disulfide bonds. As such, the side
      chain of Val1 is located close to the aromatic rings of Trp16 and His20, which
      are located on the canonical helix that displays several residues found to be
      essential for VGSC blockade in related MU-conotoxins. Mutations of residues 2 and
      3 in the N-terminal extension enhanced the potency of MU-BuIIIB for NaV1.3. One
      analogue, [d-Ala2]BuIIIB, showed a 40-fold increase, making it the most potent
      peptide blocker of this channel characterized to date and thus a useful new tool
      with which to characterize this channel. On the basis of previous results for
      related MU-conotoxins, the dramatic effects of mutations at the N-terminus were
      unanticipated and suggest that further gains in potency might be achieved by
      additional modifications of this region. 

PMID- 23557678
TI  - Routine pharmacological venous thromboembolism prophylaxis in frail older
      hospitalised patients: where is the evidence?
AB  - It has been claimed that there are over 25,000 preventable in-hospital deaths
      from venous thromboembolism annually in the UK. NICE and SIGN guidelines
      therefore recommend that all hospitalised patients are risk assessed for venous
      thromboembolism. The guidelines would recommend using pharmacological
      thromboprophylaxis for all patients aged 60 and above with reduced mobility and
      acute medical illness unless obvious contra-indications exist. Meta-analysis data
      regarding pharmacological thromboprophylaxis for medical patients demonstrate
      reductions in asymptomatic deep vein thrombosis (DVT) rather than fatal pulmonary
      embolism and mortality. There is also the potential for increased bleeding risk
      with this approach. Evidence for older medical in-patients, particularly those
      aged over 75, is more limited being derived from subgroup analyses of larger
      clinical trials. In addition, based on exclusion criteria such as increased
      bleeding risk, frailer older adults were unlikely to have been included within
      such trials. This commentary will (i) critically appraise available data on the
      incidence of DVT and PE in older hospitalised patients; (ii) review the evidence
      available from meta-analyses and subgroup analyses in older medical in-patients
      for the use of venous thromboembolism prophylaxis; (iii) discuss those situations
      out-with the guidelines where venous thromboprophylaxis may not be appropriate
      and even potentially harmful in this patient group and (iv) suggest future
      research directions.

PMID- 23557679
TI  - Cardiovascular disease in elderly.

PMID- 23557680
TI  - High expression of PP2A-Aalpha is associated with diapause induction during the
      photoperiod-sensitive stage of the cotton bollworm, Helicoverpa armigera.
AB  - Protein phosphatase 2A (PP2A) is a major serine-threonine protein phosphatase
      which regulates metabolism, transcription, RNA splicing, translation,
      differentiation, cell cycle, oncogenic transformation and signal transduction.
      PP2A-Aalpha, an isoform of PP2A-A, is a structural subunit of the PP2A complex.
      We identified the photoperiod-sensitive stage for pupal diapause induction to be
      from the fifth instar to the early sixth instar larvae in the cotton bollworm,
      Helicoverpa armigera. PP2A-Aalpha cDNA from brains of diapause-destined fifth
      instar larvae was obtained by suppressive subtractive hybridization using
      nondiapause-destined larval brains as a control. Developmental expression of PP2A
      Aalpha mRNA during the photoperiod-sensitive stage was higher in brains of
      diapause-destined larvae, and the PP2A-Aalpha protein showed a similar expression
      pattern as the mRNA. When larvae were transferred from diapause-inducing short
      days to long days during the diapause-sensitive stage, both PP2A-Aalpha mRNA and
      protein decreased significantly, and diapause incidence was also reduced. Thus,
      high PP2A-Aalpha expression during the diapause-sensitive stage may play a
      crucial role in photoperiodic induction of diapause, suggesting that it may be a
      new player involved in the molecular mechanism for diapause induction.

PMID- 23557681
TI  - Characterization of hemocytes proliferation in larval silkworm, Bombyx mori.
AB  - Hemocytes play multiple important roles during insect growth and development.
      Five types of hemocytes have been identified in the silkworm, Bombyx mori:
      prohemocyte, plasmatocyte, granulocyte, spherulocyte, and oenocytoid. We used the
      S-phase marker bromodeoxyuridine (BrdU) antibody along with the mitosis marker
      phosphohistone H3 (PHH3) antibody to monitor proliferation of hemocytes in vivo.
      The results indicate that silkworm hematopoiesis not only occurs in the
      circulatory system but also in hematopoietic organs (HPOs). During the 5th
      instar, the hemocyte proliferation in the circulatory system reaches a peak at
      the pre-wandering stage. Following infection by Escherichia coli, circulating
      hemocytes increase their cell divisions as demanded by the cellular immune
      response. All hemocytes, except spherulocytes, have the capacity to multiply in
      vivo. The BrdU label-retaining assay shows that a small portion of cells from the
      circulatory system and the HPOs are continuously labelled up to 9days and 4days
      respectively. A small number of long-term label retaining cells (LRCs)
      quiescently locate in circulatory system. All results indicate that there are a
      few quiescent stem cells or some progenitors in the larval circulatory system and
      HPO that produce new hemocytes and continuously release them into the circulating
      system.

PMID- 23557682
TI  - Functional polyelectrolyte multilayer membranes for water purification
      applications.
AB  - A diverse set of supported multilayer assemblies with controllable surface
      charge, hydrophilicity, and permeability to water and solute was fabricated by
      pressure driven permeation of poly(sodium 4-styrenesulfonate) (PSS) and
      poly(diallyldimethylammonium chloride) (PDDA) solution through poly(ethylene
      terephthalate) (PET) track-etched membranes. The polyelectrolyte multilayer
      fabrication was confirmed by means of FTIR, SEM, AFM, ellipsometry,
      zetapotential, and contact angle characterization. The prepared membranes were
      characterized in terms of their pure water permeability, flux recovery, and
      resistance to organic and biofouling properties. The antifouling behavior of the
      membranes was assessed in terms of protein adsorption and antibacterial behavior.
      Finally, the membranes were tested for rejection of selected water soluble dyes
      to establish their usefulness for organic contaminant removal from water. The
      membranes were highly selective and capable of nearly complete rejection of congo
      red with sufficiently high fluxes. The feasibility of regenerating the prepared
      membranes fouled by protein was also demonstrated and good flux recovery was
      obtained. In summary, the multilayer approach to surface and pore modification
      was shown to enable the design of membranes with the unique combination of
      desirable separation characteristics, regenerability of the separation layer, and
      antifouling behavior.

PMID- 23557683
TI  - Molecular characterization and distribution of Haemoproteus minutus
      (Haemosporida, Haemoproteidae): a pathogenic avian parasite.
AB  - Recently, the lineage hTURDUS2 of Haemoproteus minutus (Haemosporida,
      Haemoproteidae) was reported to cause mortality in captive parrots. This parasite
      lineage is widespread and prevalent in the blackbird Turdus merula throughout its
      entire distribution range. Species identity of other closely related lineages
      recently reported in dead parrots remains unclear, but will be important to
      determine for a better understanding of the epidemiology of haemoproteosis. Using
      polymerase chain reaction (PCR)-based and microscopic methods, we analyzed 265
      blood samples collected from 52 species of wild birds in Eurasia (23 samples from
      Kamchatka Peninsula, 73 from Sakhalin Island, 150 from Ekaterinburg and 19 from
      Irkutsk regions of Russia). Single infections of the lineages hTURDUS2 (hosts are
      redwing Turdus iliacus and fieldfare Turdus pilaris), hTUPHI1 (song thrush Turdus
      philomelos) and hTUCHR01 (fieldfare, redwing, song thrush and brown-headed thrush
      Turdus chysolaus) were detected. We identified species of these haemoproteids
      based on morphology of their blood stages and conclude that these lineages belong
      to H. minutus, a widespread parasite of different species of thrushes (genus
      Turdus), which serve as reservoir hosts of this haemoproteid infection.
      Phylogenetic analysis shows that the lineages hTURDUS2, hTUCHR01 and hTUPHI1 of
      H. minutus are closely related to Haemoproteus pallidus (lineages hPFC1 and
      hCOLL2), Haemoproteus pallidulus (hSYAT03), and Haemoproteus sp. (hMEUND3);
      genetic distance among their mitochondrial cytochrome b (cyt b) lineages is small
      (<1% or<4 nucleotides). All these blood parasites are different in many
      morphological characters, but are similar due to one feature, which is the pale
      staining of their macrogametocytes' cytoplasm with Giemsa. Because of the recent
      publications about mortality caused by the lineages hTUPHI1 and hTURDUS2 of H.
      minutus in captive parrots in Europe, H. minutus and the closely related H.
      pallidus and H. pallidulus are worth more attention as these are possible agents
      of haemoproteosis in exotic birds. The present study provides barcodes for
      molecular detection of different lineages of H. minutus, and extends information
      about the distribution of this blood parasite.

PMID- 23557684
TI  - Multiple clustered dermatofibromas.

PMID- 23557685
TI  - Pragmatic use of language by children who develop schizophrenia in adult life.
AB  - At eleven years of age all children in a UK national birth cohort wrote short
      stories about the life they expected to be leading at age 25. Using a data
      linkage exercise, we identified those who later developed schizophrenia,
      affective psychosis, or other non-psychotic psychiatric disorders in later life
      based on the PSE CATEGO diagnostic system. The majority of these had completed
      the written essays. Controls from the reference population were selected, matched
      for gender, IQ and social and economic status. The essays were scored using well
      established methods for assessing pragmatic use of language, namely narrative
      coherence and linguistic cohesion. We hypothesised that children pre-morbid for
      schizophrenia (Pre-Scz) would obtain low scores on all these measures. However
      this general hypothesis was largely disproved by the data, although some
      unpredicted gender effects were found. It is concluded that thought is organised
      in an unexceptional way in adolescents before they develop schizophrenia, once
      the data are corrected for any lowering of general cognitive ability in the Pre
      Scz cases.

PMID- 23557686
TI  - Does 4-tert-octylphenol affect estrogen signaling pathways in bank vole Leydig
      cells and tumor mouse Leydig cells in vitro?
AB  - Primary Leydig cells obtained from bank vole testes and the established tumor
      Leydig cell line (MA-10) have been used to explore the effects of 4-tert
      octylphenol (OP). Leydig cells were treated with two concentrations of OP (10(-4)
      M, 10(-8) M) alone or concomitantly with anti-estrogen ICI 182,780 (1 MUM). In OP
      treated bank vole Leydig cells, inhomogeneous staining of estrogen receptor alpha
      (ERalpha) within cell nuclei was found, whereas it was of various intensity among
      MA-10 Leydig cells. The expression of ERalpha mRNA and protein decreased in both
      primary and immortalized Leydig cells independently of OP dose. ICI partially
      reversed these effects at mRNA level while at protein level abrogation was found
      only in vole cells. Dissimilar action of OP on cAMP and androgen production was
      also observed. This study provides further evidence that OP shows estrogenic
      properties acting on Leydig cells. However, its effect is diverse depending on
      the cellular origin.

PMID- 23557687
TI  - Global gene expression analysis reveals pathway differences between teratogenic
      and non-teratogenic exposure concentrations of bisphenol A and 17beta-estradiol
      in embryonic zebrafish.
AB  - Transient developmental exposure to 0.1MUM bisphenol A (BPA) results in larval
      zebrafish hyperactivity and learning impairments in the adult, while exposure to
      80MUM BPA results in teratogenic responses, including craniofacial abnormalities
      and edema. The mode of action underlying these effects is unclear. We used global
      gene expression analysis to identify candidate genes and signaling pathways that
      mediate BPA's developmental toxicity in zebrafish. Exposure concentrations were
      selected and anchored to the positive control, 17beta-estradiol (E2), based on
      previously determined behavioral or teratogenic phenotypes. Functional analysis
      of differentially expressed genes revealed distinct expression profiles at 24h
      post fertilization for 0.1MUM versus 80MUM BPA and 0.1MUM versus 15MUM E2
      exposure, identification of prothrombin activation as a top canonical pathway
      impacted by both 0.1MUM BPA and 0.1MUM E2 exposure, and suppressed expression of
      several genes involved in nervous system development and function following
      0.1MUM BPA exposure.

PMID- 23557688
TI  - Environmental pesticide exposure modulates cytokines, arginase and ornithine
      decarboxylase expression in human placenta.
AB  - To evaluate the cytokine balance and enzymatic alterations induced by
      environmental pesticide exposure during pregnancy, this transversal study
      explored placentas derived from non-exposed women (control group-CG), and from
      women living in a rural area (rural group-RG), collected during intensive
      organophosphate (OP) pesticide spraying season (RG-SS) and during non-spraying
      season (RG-NSS). The exposure biomarkers blood cholinesterase and placental
      carboxylesterase (CaE) were significantly decreased in RG-SS. Among the cytokines
      studied IL-8, IL-6, TNFalpha, IL-10, TGFbeta and IL-13, the expression frequency
      of IL-13 increased in RG-SS. Arginase and ornithine decarboxylase (ODC) enzymes
      were induced in syncytiotrophoblast and endothelial cells. Interestingly, the
      decrease in CaE activity was associated with arginase and ODC activity induction.
      These findings suggest that environmental pesticide exposure impacts the placenta
      by increasing the expression frequency of the anti-inflammatory cytokine IL-13,
      which may be related to the up-regulation of enzymes implicated in tissue repair.

PMID- 23557689
TI  - Changes in steroid metabolism among girls with precocious puberty may not be
      associated with urinary levels of bisphenol A.
AB  - Precocious puberty (PP) refers to the appearance of physical and hormonal signs
      of pubertal development at an abnormally early age. Urinary steroid signatures
      obtained from 42 patients with central PP and 40 patients with peripheral PP were
      assessed to compare metabolic changes. Levels of androgens such as testosterone,
      androstenedione, androstenediol, 16alpha-hydroxy-dehydroepiandrosterone, and
      5alpha-androstenedione tended to be high in both PP groups, and the level of
      17beta-estradiol was higher in the central-PP group (P<0.01) than in the
      peripheral-PP and 32 age-matched healthy girls. Altered steroid metabolism was
      also associated with urinary BPA levels, and levels of testosterone, 17beta
      estradiol, and pregnenolone were significantly increased among individuals with
      high BPA levels. In particular, a correlation was observed between estrogen
      metabolism and BPA levels irrespective of the type of PP. These findings suggest
      that in girls, BPA exposure causes metabolic changes in steroidogenesis, but not
      the early onset of PP. 

PMID- 23557690
TI  - The great medical imitator: a case of syphilitic osteitis in the setting of HIV
      infection.
AB  - A 44-year-old man with well-controlled HIV presented with low-grade fever,
      pharyngitis, frontal headache, abdominal and shin pain, and abnormal liver
      function tests 8 weeks after switching from zidovudine to abacavir (while
      continuing nevirapine and lamivudine). An abacavir reaction was the working
      diagnosis and thus his antiretroviral regimen was returned to the previously
      tolerated combination and he received 10 days of oral penicillin (500mg twice
      daily) for presumptive tonsillitis with significant improvement. A whole-body
      bone scan demonstrated multiple foci of increased patchy osteoblastic activity of
      the long bones and skull. Six months later during routine screening, a syphilis
      rapid plasma reagin (RPR) titre of 128 was detected. Retrospective testing on
      stored samples demonstrated a first positive RPR at the time of symptomatic
      presentation. He received three injections of 1.8g benzathine penicillin on a
      weekly basis with a subsequent decrease in RPR titre and normalisation of the
      bone scan. Although syphilitic osteitis is rare, this case re-emphasises the
      importance of considering syphilis when HIV-infected patients present with
      unusual symptoms. The use of bone scan in this setting and treatment options are
      discussed.

PMID- 23557691
TI  - Alcohol hangover: type and time-extension of motor function impairments.
AB  - Alcohol hangover is defined as the unpleasant next-day state following an evening
      of excessive alcohol consumption. Hangover begins when ethanol is absent in
      plasma and is characterized by physical and psychological symptoms. During
      hangover cognitive functions and subjective capacities are affected along with
      inefficiency, reduced productivity, absenteeism, driving impairments, poor
      academic achievement and reductions in motor coordination. The aim of this work
      was to study the type and length of motor and exploratory functions from the
      beginning to the end of the alcohol hangover. Male Swiss mice were injected i.p.
      either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover
      group). Motor performance, walking deficiency, motor strength, locomotion and
      exploratory activity were evaluated at a basal point (ZT0) and every 2 h up to 20
      h after blood alcohol levels were close to zero (hangover onset). Motor
      performance was 80% decreased at the onset of hangover (p<0.001). Hangover mice
      exhibited a reduced motor performance during the next 16 h (p<0.01). Motor
      function was recovered 20 h after hangover onset. Hangover mice displayed walking
      deficiencies from the beginning to 16 h after hangover onset (p<0.05). Moreover,
      mice suffering from a hangover, exhibited a significant decrease in neuromuscular
      strength during 16 h (p<0.001). Averaged speed and total distance traveled in the
      open field test and the exploratory activity on T-maze and hole board tests were
      reduced during 16 h after hangover onset (p<0.05). Our findings demonstrate a
      time-extension between 16 to 20 h for hangover motor and exploratory impairments.
      As a whole, this study shows the long lasting effects of alcohol hangover.

PMID- 23557692
TI  - Effect of voluntary physical exercise and post-training epinephrine on
      acquisition of a spatial task in the barnes maze.
AB  - A number of experiments have shown that physical exercise improves acquisition
      and retention for a variety of learning tasks in rodents. Most of these works
      have been conducted with tasks associated with a considerable level of stress,
      physical effort and/or food deprivation that might interact with exercise, thus
      hindering the interpretation of the results. On the other hand, it is well
      established that post-training epinephrine is able to facilitate memory
      consolidation, but only a few works have studied its effect on the process of
      acquisition. The present work was aimed at studying whether 17 days of voluntary
      physical exercise (running wheels) and/or post-training epinephrine (0.01 or 0.05
      mg/kg) could improve the acquisition of a spatial task in the Barnes maze, and
      whether the combination of the two treatments have additive effects. Our results
      showed that exercise improved acquisition, and 0.01 mg/kg of epinephrine tended
      to enhance it, by reducing the distance needed to find the escape hole. The
      combination of both treatments failed to further improve the acquisition level.
      We concluded that both treatments exerted their effect on acquisition by
      enhancing the process of learning itself, and that exercise is able to improve
      acquisition even using tasks with a low level of stress and physical effort.

PMID- 23557693
TI  - Dichotomy in the anxiolytic versus antidepressant effect of C-terminal truncation
      of the GluN2A subunit of NMDA receptors.
AB  - The glutamate system is thought to play an important role in modulating mood and
      anxiety. Ionotropic NMDA receptors critically influence neuronal circuits
      regulating emotional behaviour. Their pharmacological blockade triggers fast
      antidepressant and anxiolytic effects. In line with this concept, ablation of the
      GluN2A subunit of NMDA receptors induces antidepressant and anxiolytic effects.
      However, it is not known if absence of the GluN2A-containing NMDA channel or of
      the GluN2A-mediated intracellular signalling is responsible for these effects. To
      further investigate the contribution of the GluN2A-containing NMDA receptors in
      mood disorders we analysed mice lacking the intracellular C-terminus of the
      GluN2A subunit (GluN2ADeltaC/DeltaC) in tests relevant for anxiety and
      depression. Interestingly, GluN2ADeltaC/DeltaC mice showed decreased anxiety, but
      no anti-depressive-like phenotype, indicating a predominant role of the
      intracellular signalling of the GluN2A subunit in anxiety. These data suggest
      distinct roles of the GluN2A subunit as whole vs. its intracellular domain in
      modulating anxiety and depression-like symptoms and reveal differential molecular
      targets for the therapy of mood and anxiety disorders.

PMID- 23557694
TI  - Effect of subtype-selective adenosine receptor antagonists on basal or
      haloperidol-regulated striatal function: studies of exploratory locomotion and c
      Fos immunoreactivity in outbred and A(2A)R KO mice.
AB  - Behavioral activation is regulated by dopamine (DA) in striatal areas. At low
      doses, while typical antipsychotic drugs produce psychomotor slowing,
      psychostimulants promote exploration. Minor stimulants such as caffeine, which
      act as adenosine receptor antagonists, can also potentiate behavioral activation.
      Striatal areas are rich in adenosine and DA receptors, and adenosine A2A
      receptors are mainly expressed in the striatum where they are co-localized with
      DA D2 receptors. Adenosine antagonists with different receptor-selectivity
      profiles were used to study spontaneous or haloperidol-impaired exploration and c
      Fos expression in different striatal areas. Because A2A antagonists were expected
      to be more selective for reversing the effects of the D2 antagonist haloperidol,
      A2A receptor knockout (A2ARKO) mice were also assessed. CD1 and A2ARKO male mice
      were tested in an open field and in a running wheel. Only the A1/A2A receptor
      antagonist theophylline (5.0-15.0 mg/kg) and the A2A antagonist MSX-3 (2.0 mg/kg)
      increased spontaneous locomotion and rearing. Co-administration of theophylline
      (10.0-15.0 mg/kg), and MSX-3 (1.0-3.0 mg/kg) reversed haloperidol-induced
      suppression of locomotion. The A1 antagonist CPT was only marginally effective in
      reversing the effects of haloperidol. Although adenosine antagonists did not
      affect c-Fos expression on their own, theophylline and MSX-3, but not CPT,
      attenuated haloperidol induction of c-Fos expression. A2ARKO mice were resistant
      to the behavioral effects of haloperidol at intermediate doses (0.1 mg/kg) in the
      open field and in the running wheel. A2A receptors are important for regulating
      behavioral activation, and interact with D2 receptors in striatal areas to
      regulate neural processes involved in exploratory activity.

PMID- 23557695
TI  - p,p'-Methoxyl-diphenyl diselenide protects against amyloid-beta induced
      cytotoxicity in vitro and improves memory deficits in vivo.
AB  - Behavioral evidence suggests that the organoselenium compound p,p'-methoxyl
      diphenyl diselenide [(MeOPhSe)2] ameliorates memory and learning performance in
      rodents. Here, we investigated the molecular mechanism of (MeOPhSe)2
      neuroprotection in cortical neurons exposed to amyloid-beta (Abeta) peptide as
      well as in Abeta-infused mice. For this purpose, primary cultures of rat cortical
      neurons were pre-incubated with 10 MUM of (MeOPhSe)2 or vehicle, followed by
      exposure to 25 MUM Abeta fragment 25-35 or vehicle. Furthermore, the therapeutic
      effect of (MeOPhSe)2 (5 mg/kg, oral route, daily for 5 days) on memory deficits
      was evaluated in mice exposed to Abeta fragment 25-35 (3 nmol/3 MUl/per site,
      intracerebroventricular infusion). The results demonstrate that (MeOPhSe)2
      prevented Abeta-induced cell death in vitro, associated with inhibition of
      caspase-3 and -9 activities, poly (ADP-ribose) polymerase (PARP) cleavage and c
      Jun N-terminal kinase (JNK) activation. Further, (MeOPhSe)2 rescued Abeta-induced
      memory impairment in mice. In conclusion, (MeOPhSe)2 is neuroprotective in vitro
      and in vivo, suggesting that this organoselenium compound offers a potential
      treatment option for Alzheimer's disease.

PMID- 23557696
TI  - Dyslipidaemia in juvenile dermatomyositis: the role of disease activity.
AB  - OBJECTIVES: To evaluate the presence of dyslipidaemia in JDM and its possible
      risk factors. METHODS: Twenty-five JDM patients were compared to 25 healthy
      controls according to demographic data, body composition, fasting lipoproteins,
      glycaemia, insulin, antibodies and muscle enzymes. JDM scores were assessed:
      CMAS, MMT, DAS, MYOACT and MYTAX. RESULTS: Abnormal lipid profile was found in
      nine patients and four controls (36% vs. 16%, p=0.196). JDM patients demonstrated
      significant higher levels of triglycerides (TG) [80(31-340) vs. 61(19-182) mg/dL,
      p=0.011] and higher frequency of abnormal levels of high density lipoproteins
      (HDL) (28% vs. 4%, p=0.04) when compared to controls. JDM patients with
      dyslipidaemia demonstrated significant lower median of HDL levels [29(0-49) vs.
      50(39-72) mg/dL, p=0.0005], higher frequency of low HDL levels (77% vs. 0%,
      p=0.0001), higher TG levels [128(31-340) vs. 69(46-138) mg/dL, p=0.011], and also
      a higher frequency of increased levels of TG (44% vs. 0%, p=0.01), and TC (33%
      vs. 0%, p=0.03) when compared to those without this condition. Positive anti-LPL
      antibody was detected in just one JDM patient with abnormal lipid profile. JDM
      with dyslipidaemia had higher ESR (26 vs. 1 4.5mm/1sthour, p=0.006), CRP (2.1 vs.
      0.4mg/dL, p=0.01), DAS (6 vs. 2, p=0.008), MYOACT(0.13 vs. 0.01, p=0.012),
      MYTAX(0.06vs.0,p=0.018), and lower scores of CMAS (47 vs. 52, p=0.024) and MMT
      (78 vs. 80, p=0.001) compared to JDM without dyslipidaemia. Positive correlations
      were detected between TG levels and CRP (r=0.697, p=0.001), DAS (r=0.610,
      p=0.001), MYOACT (r=0.661, p=0.001), MYTAX (r=0.511, p=0.008), and negative
      correlations with CMAS (r=-0.506, p=0.009) and MMT (r=-0.535, p=0.005). No
      differences were found between these groups regarding body composition,
      lipodystrophy, anti-LPL antibodies, and treatment except by higher frequency of
      cyclosporine current use in patients with dyslipidaemia (33% vs. 0%, p=0.03).
      CONCLUSIONS: Dyslipidaemia in JDM patients was characterised by increased levels
      of TG and low levels of HDL. Disease activity and cyclosporine use were the
      mainly factors associated to these abnormalities.

PMID- 23557697
TI  - A microbiology-based multi-parametric approach towards assessing biological
      stability in drinking water distribution networks.
AB  - Biological stability of drinking water implies that the concentration of
      bacterial cells and composition of the microbial community should not change
      during distribution. In this study, we used a multi-parametric approach that
      encompasses different aspects of microbial water quality including microbial
      growth potential, microbial abundance, and microbial community composition, to
      monitor biological stability in drinking water of the non-chlorinated
      distribution system of Zurich. Drinking water was collected directly after
      treatment from the reservoir and in the network at several locations with varied
      average hydraulic retention times (6-52 h) over a period of four months, with a
      single repetition two years later. Total cell concentrations (TCC) measured with
      flow cytometry remained remarkably stable at 9.5 (+/- 0.6) * 10(4) cells/ml from
      water in the reservoir throughout most of the distribution network, and during
      the whole time period. Conventional microbial methods like heterotrophic plate
      counts, the concentration of adenosine tri-phosphate, total organic carbon and
      assimilable organic carbon remained also constant. Samples taken two years apart
      showed more than 80% similarity for the microbial communities analysed with
      denaturing gradient gel electrophoresis and 454 pyrosequencing. Only the two
      sampling locations with the longest water retention times were the exceptions
      and, so far for unknown reasons, recorded a slight but significantly higher TCC
      (1.3 (+/- 0.1) * 10(5) cells/ml) compared to the other locations. This small
      change in microbial abundance detected by flow cytometry was also clearly
      observed in a shift in the microbial community profiles to a higher abundance of
      members from the Comamonadaceae (60% vs. 2% at other locations). Conventional
      microbial detection methods were not able to detect changes as observed with flow
      cytometric cell counts and microbial community analysis. Our findings demonstrate
      that the multi-parametric approach used provides a powerful and sensitive tool to
      assess and evaluate biological stability and microbial processes in drinking
      water distribution systems.

PMID- 23557698
TI  - Influence of sampling strategies on the estimated nitrous oxide emission from
      wastewater treatment plants.
AB  - In the last few years, the emission of nitrous oxide from wastewater treatment
      plants has become a topic of increased interest, given its considerable impact on
      the overall climate footprint of wastewater treatment plants. Various sampling
      strategies to estimate nitrous oxide emission from wastewater treatment plants
      have been applied in different studies. The present study addresses the influence
      of sampling strategies on the estimated emission by analysing the variability of
      an extensive dataset of nitrous oxide emissions resulting from a long-term online
      monitoring campaign at a full-scale municipal wastewater treatment plant. It is
      shown that short-term sampling is inadequate to accurately estimate the average
      nitrous oxide emissions from a particular wastewater treatment plant, while
      online monitoring is indispensable to capture the short-term variability (diurnal
      dynamics).

PMID- 23557699
TI  - Counselling improves follow-up HIV testing at Week 6 for HIV postexposure
      prophylaxis recipients.
AB  - Demographic and clinical variables of clients attending a sexual health centre in
      western Sydney from 1 July 2009 to 30 June 2011 were examined to determine if
      nonoccupational HIV postexposure prophylaxis (NPEP) was being dispensed according
      to national guidelines,(1) and to identify factors associated with completion of
      follow-up. The results showed that 95.8% of antiretroviral prescriptions were
      consistent with national guidelines.(1) Consultation with a social worker
      significantly improved attendance for six week follow up serology (P=0.027).

PMID- 23557700
TI  - FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis
      in rats and mice.
AB  - Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) and
      play an integral role in the regulation of glucose, energy homeostasis, and the
      development of obesity and diabetes. Using pharmacologic agents, we previously
      found that ~50% of these neurons responded to oleic acid (OA) by using the FA
      translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of
      CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted
      using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA
      (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36
      depletion, the percent of neurons that responded to OA was decreased specifically
      in glucosensing neurons. A similar effect was seen in total-body CD36-knockout
      mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite
      significant VMH CD36 depletion, there was no effect on food intake, body weight
      gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36
      depleted rats did have increased plasma leptin and subcutaneous fat deposition
      and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a
      critical factor in both VMH neuronal FA sensing and the regulation of energy and
      glucose homeostasis.

PMID- 23557701
TI  - Potential of protein phosphatase inhibitor 1 as biomarker of pancreatic beta-cell
      injury in vitro and in vivo.
AB  - There is a need for plasma-based tests that can directly measure the extent of
      beta-cell injury in vivo in patients receiving islet grafts and in animal models.
      In this study, we propose protein phosphatase 1, regulatory (inhibitor) subunit
      1A (PPP1R1A) as a novel biomarker for acute beta-cell destruction. Liquid
      chromatography-tandem mass spectrometry proteome analysis of fluorescence
      activated cell sorter-purified beta-cells, tissue-comparative Western blotting,
      and immunohistochemistry indicated relatively high molar abundance and
      selectivity of PPP1R1A in beta-cells. PPP1R1A was discharged into the
      extracellular space of chemically injured rat and human islets in vitro,
      proportionate to the extent of beta-cell death. Streptozotocin injection in rats
      led to a progressive PPP1R1A depletion from the cytoplasm of disintegrating beta
      cells and a marked surge in plasma levels detectable by an affinity-capture
      method. A similar massive PPP1R1A discharge in blood was also detected in three
      patients immediately after intraportal islet transplantation. Our findings
      provide first proof-of-principle for PPP1R1A as real-time biomarker of beta-cell
      destruction in animal models and patients and warrant development of more
      sensitive methods for its further validation in clinical trials. 

PMID- 23557702
TI  - PKCdelta impaired vessel formation and angiogenic factor expression in diabetic
      ischemic limbs.
AB  - Decreased collateral vessel formation in diabetic peripheral limbs is
      characterized by abnormalities of the angiogenic response to ischemia.
      Hyperglycemia is known to activate protein kinase C (PKC), affecting the
      expression and activity of growth factors such as vascular endothelial growth
      factor (VEGF) and platelet-derived growth factor (PDGF). The current study
      investigates the role of PKCdelta in diabetes-induced poor collateral vessel
      formation and inhibition of angiogenic factors expression and actions. Ischemic
      adductor muscles of diabetic Prkcd(+/+) mice exhibited reduced blood reperfusion,
      vascular density, and number of small vessels compared with nondiabetic
      Prkcd(+/+) mice. By contrast, diabetic Prkcd(-/-) mice showed significant
      increased blood flow, capillary density, and number of capillaries. Although
      expression of various PKC isoforms was unchanged, activation of PKCdelta was
      increased in diabetic Prkcd(+/+) mice. VEGF and PDGF mRNA and protein expression
      were decreased in the muscles of diabetic Prkcd(+/+) mice and were normalized in
      diabetic Prkcd(-/-) mice. Furthermore, phosphorylation of VEGF receptor 2
      (VEGFR2) and PDGF receptor-beta (PDGFR-beta) were blunted in diabetic Prkcd(+/+)
      mice but elevated in diabetic Prkcd(-/-) mice. The inhibition of VEGFR2 and PDGFR
      beta activity was associated with increased SHP-1 expression. In conclusion, our
      data have uncovered the mechanisms by which PKCdelta activation induced poor
      collateral vessel formation, offering potential novel targets to regulate
      angiogenesis therapeutically in diabetic patients. 

PMID- 23557703
TI  - Effects of common genetic variants associated with type 2 diabetes and glycemic
      traits on alpha- and beta-cell function and insulin action in humans.
AB  - Although meta-analyses of genome-wide association studies have identified >60
      single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and/or
      glycemic traits, there is little information on whether these variants also
      affect alpha-cell function. The aim of the current study was to evaluate the
      effects of glycemia-associated genetic loci on islet function in vivo and in
      vitro. We studied 43 SNPs in 4,654 normoglycemic participants from the Finnish
      population-based Prevalence, Prediction, and Prevention of Diabetes-Botnia (PPP
      Botnia) Study. Islet function was assessed, in vivo, by measuring insulin and
      glucagon concentrations during oral glucose tolerance test, and, in vitro, by
      measuring glucose-stimulated insulin and glucagon secretion from human pancreatic
      islets. Carriers of risk variants in BCL11A, HHEX, ZBED3, HNF1A, IGF1, and NOTCH2
      showed elevated whereas those in CRY2, IGF2BP2, TSPAN8, and KCNJ11 showed
      decreased fasting and/or 2-h glucagon concentrations in vivo. Variants in BCL11A,
      TSPAN8, and NOTCH2 affected glucagon secretion both in vivo and in vitro. The
      MTNR1B variant was a clear outlier in the relationship analysis between insulin
      secretion and action, as well as between insulin, glucose, and glucagon. Many of
      the genetic variants shown to be associated with type 2 diabetes or glycemic
      traits also exert pleiotropic in vivo and in vitro effects on islet function. 

PMID- 23557704
TI  - beta-Cell lipotoxicity in response to free fatty acid elevation in prepubertal
      youth: African American versus Caucasian contrast.
AB  - Prepubertal African American (AA) youth compared with their Caucasian (C) peers
      have higher insulin secretion, which correlates positively with free fatty acid
      (FFA) concentration. In our continued efforts to explain the racial disparity in
      insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA
      youth would have a greater response to FFA-induced beta-cell insulin secretion
      than C youth. We compared the short-term effects of FFA elevation on fasting and
      glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal
      weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two
      occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL).
      During IL infusion, insulin sensitivity (IS) declined comparably in AA and C
      youth. Glucose sensitivity of first- and second-phase insulin secretion showed a
      significant condition * race interaction being higher in AA youth. Disposition
      index, beta-cell function relative to IS, declined with IL infusion in AA and C
      youth, with a significantly greater decrease in Cs compared with AAs. In
      conclusion, AA and C prepubertal youth both demonstrated a decline in beta-cell
      function relative to IS during IL infusion, indicative of acute lipotoxicity. The
      greater decline in C youth compared with AAs may suggest that C youth are more
      susceptible to beta-cell lipotoxicity than AA youth, or alternatively, that AA
      youth are hypersensitive to FFA stimulation of beta-cell insulin secretion,
      consistent with our theory. 

PMID- 23557706
TI  - Mammalian target of rapamycin regulates Nox4-mediated podocyte depletion in
      diabetic renal injury.
AB  - Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin
      that eventuates in kidney fibrosis. Pharmacological doses of the mammalian target
      of rapamycin (mTOR) inhibitor rapamycin reduce albuminuria in diabetes. We
      explored the hypothesis that mTOR mediates podocyte injury in diabetes. High
      glucose (HG) induces apoptosis of podocytes, inhibits AMP-activated protein
      kinase (AMPK) activation, inactivates tuberin, and activates mTOR. HG also
      increases the levels of Nox4 and Nox1 and NADPH oxidase activity. Inhibition of
      mTOR by low-dose rapamycin decreases HG-induced Nox4 and Nox1, NADPH oxidase
      activity, and podocyte apoptosis. Inhibition of mTOR had no effect on AMPK or
      tuberin phosphorylation, indicating that mTOR is downstream of these signaling
      molecules. In isolated glomeruli of OVE26 mice, there is a similar decrease in
      the activation of AMPK and tuberin and activation of mTOR with increase in Nox4
      and NADPH oxidase activity. Inhibition of mTOR by a small dose of rapamycin
      reduces podocyte apoptosis and attenuates glomerular injury and albuminuria. Our
      data provide evidence for a novel function of mTOR in Nox4-derived reactive
      oxygen species generation and podocyte apoptosis that contributes to urinary
      albumin excretion in type 1 diabetes. Thus, mTOR and/or NADPH oxidase inhibition
      may represent a therapeutic modality of diabetic kidney disease. 

PMID- 23557705
TI  - Identification of a loss-of-function mutation in Ube2l6 associated with obesity
      resistance.
AB  - We previously mapped a locus on BALB/c chromosome 2 associated with protection
      from leptin-deficiency-induced obesity. Here, we generated the corresponding
      congenic mouse strain by introgression of a segment of C57BL/6J chromosome 2 to
      the BALB/c background to confirm the genotype-phenotype associations. We found
      that the BALB/c alleles decreased fat mass expansion by limiting adipocyte
      hyperplasia and adipocyte hypertrophy. This was concomitant to an increase in
      adipocyte triglyceride lipase (ATGL)-mediated triglyceride breakdown and
      prolongation of ATGL half-life in adipose tissue. In addition, BALB/c alleles on
      chromosome 2 exerted a cell-autonomous role in restraining the adipogenic
      potential of preadipocytes. Within a 9.8-Mb critical interval, we identified a
      nonsynonymous coding single nucleotide polymorphism in the gene coding for the
      ubiquitin-conjugating enzyme E2L6 (Ube2l6, also known as Ubch8) and showed that
      the BALB/c allele of Ube2l6 is a hypomorph leading to the lack of UBE2L6 protein
      expression. Ube2l6 knockdown in 3T3-L1 adipocytes repressed adipogenesis. Thus,
      altered adipogenic potential caused by Ube2l6 knockdown is likely critically
      involved in BALB/c obesity resistance by inhibiting adipogenesis and reducing
      adipocyte numbers. Overall, we have identified a loss-of-function mutation in
      Ube2l6 that contributes to the chromosome 2 obesity quantitative trait locus. 

PMID- 23557708
TI  - Evidence of tRNA cleavage in apicomplexan parasites: Half-tRNAs as new potential
      regulatory molecules of Toxoplasma gondii and Plasmodium berghei.
AB  - Several lines of evidence demonstrated that organisms ranging from bacteria to
      higher animals possess a regulated endonucleolytic cleavage pathway producing
      half-tRNA fragments. In the present study, we investigated the occurrence of this
      phenomenon in two distantly related apicomplexan parasites, Toxoplasma gondii,
      the agent of toxoplasmosis, and the rodent malaria parasite Plasmodium berghei. A
      low-scale molecular characterization of the small RNA fraction of T. gondii
      revealed the endonucleolytic processing of 10 distinct tRNA species, with
      cleavage in the anticodon loop and upstream of the 3'-terminal CCA sequence
      yielding 5'- or 3'-end half-tRNAs. T. gondii and P. berghei exhibited variable
      rates of tRNA cleavage upon egress from host cells and in response to stage
      differentiation, amino acid starvation and heat-shock. Moreover, avirulent
      isolates of T. gondii and attenuated P. berghei parasites showed a higher rate of
      tRNA cleavage than virulent strains. Interestingly, half-tRNA production was
      significantly higher in the metabolically quiescent bradyzoite and sporozoite
      stages of T. gondii, compared to the fast-growing tachyzoite. Collectively, our
      findings shed light for the first time on the occurrence of tRNA cleavage in
      apicomplexan parasites and suggest a relationship between half-tRNA production
      and growth rate in this important group of organisms.

PMID- 23557707
TI  - Association of ketone body levels with hyperglycemia and type 2 diabetes in 9,398
      Finnish men.
AB  - We investigated the association of the levels of ketone bodies (KBs) with
      hyperglycemia and with 62 genetic risk variants regulating glucose levels or type
      2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study,
      including 9,398 Finnish men without diabetes or newly diagnosed type 2 diabetes.
      Increasing fasting and 2-h plasma glucose levels were associated with elevated
      levels of acetoacetate (AcAc) and beta-hydroxybutyrate (BHB). AcAc and BHB
      predicted an increase in the glucose area under the curve in an oral glucose
      tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year
      follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin
      resistance, explained these findings. Of the 62 single nucleotide polymorphisms
      associated with the risk of type 2 diabetes or hyperglycemia, the glucose
      increasing C allele of GCKR significantly associated with elevated levels of
      fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in
      ketolysis were significantly associated with insulin sensitivity (Matsuda index).
      In conclusion, high levels of KBs predicted subsequent worsening of
      hyperglycemia, and a common variant of GCKR was significantly associated with BHB
      levels. 

PMID- 23557709
TI  - Evaluation of a polymerase chain reaction-electrospray ionization time-of-flight
      mass spectrometry for the detection and subtyping of influenza viruses in
      respiratory specimens.
AB  - BACKGROUND: PCR coupled to electrospray ionization mass spectrometry technology
      (PCR/ESI-TOF-MS) (PLEX-ID system, Abbott Ibis Biosciences) was developed to
      characterize microbial pathogens. OBJECTIVES: To evaluate the performance of the
      PLEX-ID flu detectionTM kit for detecting Influenza viruses by comparison with
      the multiplex RespiFinder((r)) Kit (PathoFinder). STUDY DESIGN: Acute-phase
      respiratory samples (n=293) were analysed for this purpose. A subpopulation of
      influenza type A positive samples, identified with the RespiFinder((r)) kit
      (n=64), were subtyped with the RealTime ready Inf A/H1N1 Detection Set((r))
      (Roche Molecular Diagnostics) and results were compared to the PLEX-ID Flu
      DetectionTM kit. RESULTS: 274 samples gave concordant results (93.5%, p<0.0001):
      65 influenza A-positive, 18 influenza B-positive and 191 negative samples. Of
      these, 7 samples were PLEX-ID positive/RespiFinder((r)) negative (5 influenza A
      and 2 influenza B) and 12 were PLEX-ID positive/RespiFinder((r)) negative (10
      influenza A and 2 influenza B). PLEX-ID showed one sample as an influenza A and B
      co-infection while the RespiFinder((r)) assay showed it to be influenza A
      positive. The sensitivity, specificity, positive and negative predictive values
      of the PLEX-IDTM system were 87.4%, 96.5%, 92.2% and 94.1% respectively. Thirteen
      of 19 discordant samples available for retesting were investigated further with
      the AnyplexTMII RV16 Detection kit (Seegene): seven were RespiFinder((r))
      concordant, while six were PLEX-IDTM concordant. Subtyping of 61/64 influenza A
      samples was concordant (95.3%): 55 were H1N1pdm09 and six were non-H1N1pdm09.
      Three samples gave negative PLEX-IDTM results (one H1N1pdm09 and two non
      H1N1pdm09). CONCLUSIONS: PCR/ESI-TOF-MS technology showed good diagnostic
      performances to detect and subtype influenza viruses.

PMID- 23557710
TI  - A neuroanatomical and neurochemical study of the indusium griseum and anterior
      hippocampal continuation: comparison with dentate gyrus.
AB  - The indusium griseum (IG) and anterior hippocampal continuation (AHC) are
      longitudinal and continuous structures that consist of two narrow strips of gray
      matter overlying the rostrocaudal length of the corpus callosum, extending
      rostrally to the genu of the corpus callosum and ventrally to the rostrum. The
      present study aimed to characterize the phenotype of neuronal innervations to the
      IG-AHC and their intra-structural topographic organization. Using
      immunohistochemistry, we found nerve fibers expressing choline acetyltransferase,
      tyrosine hydroxylase, dopamine-beta-hydroxylase, the serotonin reuptake
      transporter as well as glutamic acid decarboxylase-67 and parvalbumin. These
      suggest that the IG and AHC are innervated by acetylcholine, dopamine,
      noradrenaline, 5-hydroxytryptamine and GABA neurons. More importantly, all these
      fibers display a topographic laminar distribution in both brain areas. The
      presence of varicosities along the nerve fibers suggests that these
      neurotransmitters are released extracellullarly to exert a physiological action.
      Finally, the structural similarities with the dentate gyrus support the idea that
      the IG and AHC are anatomically associated, if not continuous, with this area and
      may represent in mammals a vestige of the hippocampus.

PMID- 23557711
TI  - An analysis of FMA using structural self-bisimilarity.
AB  - As ontologies are mostly manually created, they tend to contain errors and
      inconsistencies. In this paper, we present an automated computational method to
      audit symmetric concepts in ontologies by leveraging self-bisimilarity and
      linguistic structure in the concept names. Two concepts A and B are symmetric if
      concept B can be obtained from concept A by replacing a single modifier such as
      "left" with its symmetric modifier such as "right." All possible local structural
      types for symmetric concept pairs are enumerated according to their local
      subsumption hierarchy, and the pairs are further classified into Non-Matches and
      Matches. To test the feasibility and validate the benefits of this method, we
      computed all the symmetric modifier pairs in the Foundational Model of Anatomy
      (FMA) and selected six of them for experimentation. 9893 Non-Matches and 221
      abnormal Matches with potential errors were discovered by our algorithm. Manual
      evaluation by FMA domain experts on 176 selected Non-Matches and all the 221
      abnormal Matches found 102 missing concepts and 40 misaligned concepts.
      Corrections for them have currently been implemented in the latest version of
      FMA. Our result demonstrates that self-bisimilarity can be a valuable method for
      ontology quality assurance, particularly in uncovering missing concepts and
      misaligned concepts. Our approach is computationally scalable and can be applied
      to other ontologies that are rich in symmetric concepts.

PMID- 23557712
TI  - Intraindividual differences in executive functions during childhood: the role of
      emotions.
AB  - Intraindividual differences in executive functions (EFs) have been rarely
      investigated. In this study, we addressed the question of whether the emotional
      fluctuations that schoolchildren experience in their classroom settings could
      generate substantial intraindividual differences in their EFs and, more
      specifically, in the fundamental unifying component of EFs, their inhibition
      function. We designed an experimental research with ecological validity within
      the school setting where schoolchildren of three age groups (8-, 10-, and 12-year
      olds) were involved. We executed three experiments. In Experiment 1, using a
      between-participants design, we isolated a classroom episode that, compared with
      the other episodes, generated significant differences in inhibitory function in a
      consequent Go/NoGo task. This was an episode that induced frustration after the
      experience of anxiety due to the uncertainty. Experiment 2, using a within
      participants design, confirmed both the induced emotions from the episode and the
      intraindividual variability in schoolchildren's inhibition accuracy in the
      consequent Go/NoGo task. Experiment 3, again using a within-participants design,
      examined whether the same episode could generate intraindividual differences in a
      more demanding inhibition task, namely the anti-saccade task. The experiment
      confirmed the previous evidence; the episode generated high variability that in
      some age groups accounted for more than 1.5 standard deviations from the
      interindividual variability between the schoolchildren of the same age. Results
      showed that, regardless of their sex and the developmental progression in their
      inhibition with age, the variability induced within participants from the
      experienced frustration was very high compared with the interindividual
      variability of the same age group.

PMID- 23557713
TI  - Carbofluoresceins and carborhodamines as scaffolds for high-contrast fluorogenic
      probes.
AB  - Fluorogenic molecules are important tools for advanced biochemical and biological
      experiments. The extant collection of fluorogenic probes is incomplete, however,
      leaving regions of the electromagnetic spectrum unutilized. Here, we synthesize
      green-excited fluorescent and fluorogenic analogues of the classic fluorescein
      and rhodamine 110 fluorophores by replacement of the xanthene oxygen with a
      quaternary carbon. These anthracenyl "carbofluorescein" and "carborhodamine 110"
      fluorophores exhibit excellent fluorescent properties and can be masked with
      enzyme- and photolabile groups to prepare high-contrast fluorogenic molecules
      useful for live cell imaging experiments and super-resolution microscopy. Our
      divergent approach to these red-shifted dye scaffolds will enable the preparation
      of numerous novel fluorogenic probes with high biological utility. 

PMID- 23557714
TI  - Scaring alopecia in pemphigus vulgaris: a rare or underdiagnosed presentation?

PMID- 23557715
TI  - An experimental and theoretical study of the vibrational spectra and structure of
      Isosorbide dinitrate.
AB  - The present work aims at exploring the vibrational spectra of Isosorbide
      dinitrate and its chemical activity in a five membered ring system. The FT-IR and
      FT-Raman spectral studies of the Isosorbide dinitrate (ISDN) were carried out.
      The equilibrium geometry, various bonding features and harmonic vibrational
      frequencies of ISDN have been calculated using B3LYP density functional theory
      (DFT) with 6-31G(d,p) as basis set. The calculated HOMO and LUMO energies and
      density of states (DOS) show the chemical activity of the molecule. Good
      correlations between the experimental (1)H and (13)C NMR chemical shifts in
      methanol-d and calculated GIAO shielding tensors were found. The potential energy
      surface was studied using the DFT method.

PMID- 23557716
TI  - Fusarium avenaceum causes burn spot disease syndrome in noble crayfish (Astacus
      astacus).
AB  - Burn spot disease has been causing epidemics both in the Estonian mainland and in
      Saaremaa Island in the threatened noble crayfish (Astacus astacus) stocks. To
      study the cause of the disease, we isolated several Fusarium spp. from Estonian
      noble crayfish (A. astacus) populations suffering from burn spot disease
      syndrome. We first identified fungi directly from melanised cuticle by their ITS
      sequences. Then we isolated Fusarium spp. from melanised spots of crayfish
      showing burn spot disease symptoms, such as melanisation and shell erosion, from
      two different crayfish populations and watercourses in Estonia. The isolates were
      then identified based on ITS and EF1alpha-gene sequences. Isolates of Fusarium
      spp. taken from two separate Estonian noble crayfish populations were used in
      infection studies. Koch postulates confirmed that the studied agent was causing
      burn spot disease symptoms including shell erosion in the noble crayfish, which
      were significantly more severe after molts. After the infection period, an
      identical Fusarium spp. was re-isolated from carapace lesions and was thus shown
      to be the disease agent causing burn spot disease syndrome and shell erosion in
      noble crayfish. Based on GenBank database searches, the isolates causing burn
      spot disease symptoms were identified as Fusarium avenaceum in mainland Estonia
      and F. solani in Saaremaa crayfish.

PMID- 23557717
TI  - Identifying an ERG-positive subclass with clinical progression using expression
      profiling.

PMID- 23557718
TI  - Effective management of localized prostate cancer: first, do no harm.

PMID- 23557719
TI  - Predominant contribution of L-type amino acid transporter to 4-borono-2-(18)F
      fluoro-phenylalanine uptake in human glioblastoma cells.
AB  - INTRODUCTION: 4-Borono-2-(18)F-fluoro-phenylalanine ((18)F-FBPA) has been used to
      anticipate the therapeutic effects of boron neutron capture therapy (BNCT) with 4
      borono-L-phenylalanine (BPA). Similarly, L-[methyl-(11)C]-methionine ((11)C-MET),
      the most popular amino acid PET tracer, is a possible candidate for this purpose.
      We investigated the transport mechanism of (18)F-FBPA and compared it with that
      of (14)C-MET in human glioblastoma cell lines. METHODS: Uptake of (18)F-FBPA and
      (14)C-MET was examined in A172, T98G, and U-87MG cells using 2-aminobicyclo
      (2.2.1)-heptane-2-carboxylic acid (a system L-specific substrate), 2
      (methylamino)-isobutyric acid (a system A-specific substrate), and BPA. Gene
      expression was analyzed by quantitative real time polymerase chain reaction.
      RESULTS: System L was mainly involved in the uptake of (18)F-FBPA (74.5%-81.1% of
      total uptake) and (14)C-MET (48.3%-59.4%). System A and ASC also contributed to
      the uptake of (14)C-MET. Inhibition experiments revealed that BPA significantly
      decreased the uptake of (18)F-FBPA, whereas 31%-42% of total (14)C-MET uptake was
      transported by BPA non-sensitive transporters. In addition, (18)F-FBPA uptake
      correlated with LAT1 and total LAT expressions. CONCLUSION: This study
      demonstrated that (18)F-FBPA was predominantly transported by system L in human
      glioblastoma cells compared to (14)C-MET. Although further studies are needed to
      elucidate the correlation between (18)F-FBPA uptake and BPA content in tumor
      tissues, (18)F-FBPA is suitable for the selection of patients who benefit from
      BNCT with BPA.

PMID- 23557720
TI  - Strategies to enhance epithelial-mesenchymal interactions for human hair follicle
      bioengineering.
AB  - Hair follicle morphogenesis and regeneration depend on intensive but well
      orchestrated interactions between epithelial and mesenchymal components.
      Accordingly, the enhancement of this crosstalk represents a promising approach to
      achieve successful bioengineering of human hair follicles. The present article
      summarizes the techniques, both currently available and potentially feasible, to
      promote epithelial-mesenchymal interactions (EMIs) necessary for human hair
      follicle regeneration. The strategies include the preparation of epithelial
      components with high receptivity to trichogenic dermal signals and/or mesenchymal
      cell populations with potent hair inductive capacity. In this regard, bulge
      epithelial stem cells, keratinocytes predisposed to hair follicle fate or
      keratinocyte precursor cells with plasticity may provide favorable epithelial
      cell populations. Dermal papilla cells sustaining intrinsic hair inductive
      capacity, putative dermal papilla precursor cells in the dermal sheath/neonatal
      dermis or trichogenic dermal cells derived from undifferentiated stem/progenitor
      cells are promising candidates as hair inductive dermal cells. The most
      established protocol for in vivo hair follicle reconstitution is co-grafting of
      epithelial and mesenchymal components into immunodeficient mice. In theory,
      combination of individually optimized cellular components of respective lineages
      should elicit most intensive EMIs to form hair follicles. Still, EMIs can be
      further ameliorated by the modulation of non-cell autonomous conditions,
      including cell compartmentalization to replicate the positional relationship in
      vivo and humanization of host environment by preparing human stromal bed. These
      approaches may not always synergistically intensify EMIs, however, step-by-step
      investigation probing optimal combinations should maximally enhance EMIs to
      achieve successful human hair follicle bioengineering.

PMID- 23557721
TI  - Australian registries-ANZDATA and ANZOD.
AB  - Transplant registries are a proven valuable source of data about transplantation.
      The inclusion of all transplants conducted in a region or country provides a
      different perspective from that of other observational studies. They allow
      examination of activity levels and trends, provide descriptions of outcomes which
      avoid the selection bias inherent in randomized clinical trials and facilitate
      hypothesis-generating studies. Examination of rare or unusual diseases and their
      outcomes is another area of strength. The models and structures of registries
      vary throughout the world. In Australia and New Zealand, kidney transplant
      outcomes are combined with dialysis in the Australia and New Zealand Dialysis and
      Transplant (ANZDATA) Registry. Deceased solid-organ donor activity is recorded in
      the Australia and New Zealand Organ Donor (ANZOD) Registry. Both of these
      registries are conducted and governed along similar lines. Key factors include
      strong clinical links in data collection and governance, and the involvement of
      contributors in a wide variety of activities and output.

PMID- 23557722
TI  - Comorbidity profiles among adult patients with juvenile idiopathic arthritis:
      results of a biologic register.
AB  - OBJECTIVES: This study aims to assess the prevalence of comorbidities in adult
      JIA and the impact of comorbidity on patients' perceived health state. METHODS:
      Self-reported comorbidity was studied in 344 adult JIA patients who have been
      included in the biologic register JuMBO. The comorbidity prevalence among the
      patients was compared to an age- and sex-matched reference group from the
      population. The correlation of comorbidity with clinical and demographic
      parameters was analysed by linear or logistic regression models. RESULTS: Sixty
      two percent of the JIA patients reported at least one comorbidity. Uveitis was
      the most common comorbid condition (17.7%), followed by allergic rhinitis
      (14.5%), migraine (8.7%), and atopic dermatitis (8.7%). The prevalence of
      cardiovascular disorders was 9.9%, which was not higher than that in the
      population. However, patients with a systemic onset of JIA (soJIA) had a
      substantially higher rate of cardiovascular diseases of 40.6% (p=0.033). Patients
      with soJIA also had the highest prevalence (80.0%) and the highest mean number
      (1.8) of comorbidities. Patients with at least one comorbid condition suffered
      more often from fatigue and pain, had a lower functional capacity (p<0.001,
      each), and a lower physical and mental health-related quality of life than those
      without comorbidities (p<0.001 and p=0.017, respectively). The presence of any
      comorbidity and the level of disease activity were independent predictors of a
      lower SF-36 score. CONCLUSIONS: Our results indicate that comorbid conditions
      have a significant impact on the perceived health state in adult JIA. Among all
      JIA patients, those with systemic onset carry the highest risk for comorbidities,
      in particular for cardiovascular disorders.

PMID- 23557723
TI  - Comparative analysis of effluent water quality from a municipal treatment plant
      and two on-site wastewater treatment systems.
AB  - Though decentralized on-site technologies are extensively employed for wastewater
      treatment around the globe, an understanding of effluent water quality
      impairments associated with these systems remain less understood than effluent
      discharges from centralized municipal wastewater treatment facilities. Using a
      unique experimental facility, a novel comparative analysis of effluent water
      quality was performed from model decentralized aerobic (ATS) and septic (STS) on
      site wastewater treatment systems and a centralized municipal wastewater
      treatment plant (MTP). The ATS and STS units did not benefit from further soil
      treatment. Each system received common influent wastewater from the Waco, Texas,
      USA Metropolitan Area Regional Sewerage System. We tested the hypothesis that MTP
      effluent would exhibit higher water quality than on-site effluents, based on
      parameters selected for study. A tiered testing approach was employed to assess
      the three effluent discharges: select routine water quality parameters (Tier I),
      whole effluent toxicity (Tier II), and select endocrine-active compounds (Tier
      III). Contrary to our hypothesis, ATS effluent was not statistically different
      from MTP effluents, based on Tier I and III parameters, but reproductive
      responses of Daphnia magna were slightly more sensitive to ATS than MTP
      effluents. STS effluent water quality was identified as most degraded of the
      three wastewater treatment systems. Parameters used to assess centralized
      wastewater treatment plant effluent water quality such as whole effluent toxicity
      and endocrine active substances appear useful for water quality assessments of
      decentralized discharges. Aerobic on-site wastewater treatment systems may
      represent more robust options than traditional septic systems for on-site
      wastewater treatment in watersheds with appreciable groundwater - surface water
      exchange.

PMID- 23557724
TI  - Aging of nickel added to soils as predicted by soil pH and time.
AB  - Although aging processes are important in risk assessment for metals in soils,
      the aging of Ni added to soils has not been studied in detail. In this study,
      after addition of water soluble Ni to soils, the changes over time in isotopic
      exchangeability, total concentrations and free Ni(2+) activity in soil pore
      water, were investigated in 16 European soils incubated outdoors for 18 months.
      The results showed that after Ni addition, concentrations of Ni in soil pore
      water and isotopic exchangeability of Ni in soils initially decreased rapidly.
      This phase was followed by further decreases in the parameters measured but these
      occurred at slower rates. Increasing soil pH increased the rate and extent of
      aging reactions. Semi-mechanistic models, based on Ni precipitation/nucleation on
      soil surfaces and micropore diffusion, were developed and calibrated. The initial
      fast processes, which were attributed to precipitation/nucleation, occurred over
      a short time (e.g. 1h), afterwards the slow processes were most likely controlled
      by micropore diffusion processes. The models were validated by comparing
      predicted and measured Ni aging in three additional, widely differing soils aged
      outdoors for periods up to 15 months in different conditions. These models could
      be used to scale ecotoxicological data generated in short-term studies to longer
      aging times.

PMID- 23557725
TI  - Single Cell Gel Electrophoresis (Comet) assay with plants: research on DNA repair
      and ecogenotoxicity testing.
AB  - Single Cell Gel Electrophoresis is currently used to investigate the cell
      response to genotoxic agents as well as to several biotic and abiotic stresses
      that lead to oxidative DNA damage. Different versions of Single Cell Gel
      Electrophoresis have been developed in order to expand the range of DNA lesions
      that can be detected and guidelines for their use in genetic toxicology have been
      provided. Applications of Single Cell Gel Electrophoresis in plants are still
      limited, compared to animal systems. This technique is now emerging as a useful
      tool in assessing the potential of higher plants as stable sensors in ecosystems
      and source of information on the genotoxic impact of dangerous pollutants.
      Another interesting application of Single Cell Gel Electrophoresis deals with
      Mutation Breeding or the combined use of irradiation and in vitro culture
      technique to enhance genetic variability in elite plant genotypes. SCGE, in
      combination with in situ detection of Reactive Oxygen Species (ROS) induced by
      gamma-rays and expression analysis of both DNA repair and antioxidant genes, can
      be used to gather information on the radiosensitivity level of the target plant
      genotypes.

PMID- 23557726
TI  - Health risk assessment of pesticides residue in maize and cowpea from Ejura,
      Ghana.
AB  - Low productivity in agriculture due to damage cause by pests has led to the
      application of pesticides to control pest infestation. Residues of pesticides
      applied on crops are often found in the food which can cause chronic effect on
      the health of humans who consume such products. The aim of this study is to
      measure pesticides residues in maize and cowpea and compare the values with
      stablished safety limits. A total of 37 pesticides comprising 15 organochlorines,
      13 organophosphorus and 9 pyrethroids pesticides were identified in maize and
      cowpea samples obtained from farms in Ejura. Analytical methods included solvent
      extraction of the pesticide residues and their subsequent quantification using
      gas chromatograph equipped with Electron Capture Detector and Pulse Flame
      Photometric Detector after clean-up on alumina/activated charcoal column. The
      results showed that the mean concentration of pesticides in maize ranged from
      0.001 to 0.103 mg kg(-1) for organochlorine pesticides, 0.002-0.019 mg kg(-1) for
      organophosphorus pesticides and 0.002-0.028 mg kg(-1) for pyrethroids pesticides.
      In cowpea the mean concentration ranged from 0.001 to 0.108 mg kg(-1) for
      organochlorine pesticides, 0.002-0.015 mg kg(-1) for organophosphorus pesticides
      and 0.001-0.039 mg kg(-1) for pyrethroids pesticides. Maximum Residue Limits for
      beta-HCH, beta-endosulfan, p,p'-DDE and p,p'-DDD were exceeded in both maize and
      cowpea samples. Health risk estimation revealed that residues of heptachlor,
      dieldrin, endrin, beta-endosulfna, gamma-chlordane and chlorfenvinphos found in
      maize exceeded the Acceptable Daily Intake. Similarly the levels of heptachlor
      and p,p'-DDD found in cowpea also exceeded the Acceptable Daily Intake. This
      suggests a great potential for chronic toxicity to consumers of these food items.

PMID- 23557727
TI  - Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in
      vivo evidence.
AB  - Multiple reactive oxygen/nitrogen species induce oxidative stress. Mammals have
      evolved with an elaborate defense network against oxidative stress, in which
      multiple antioxidant compounds and enzymes with different functions exert their
      respective roles. Radical scavenging is one of the essential roles of
      antioxidants and vitamin E is the most abundant and important lipophilic radical
      scavenging antioxidant in vivo. The kinetic data and physiological molar ratio of
      vitamin E to substrates show that the peroxyl radicals are the only radicals that
      vitamin E can scavenge to break chain propagation efficiently and that vitamin E
      is unable to act as a potent scavenger of hydroxyl, alkoxyl, nitrogen dioxide,
      and thiyl radicals in vivo. The preventive effect of vitamin E against the
      oxidation mediated by nonradical oxidants such as hypochlorite, singlet oxygen,
      ozone, and enzymes may be limited in vivo. The synergistic interaction of vitamin
      E and vitamin C is effective for enhancing the antioxidant capacity of vitamin E.
      The in vitro and in vivo evidence of the function of vitamin E as a peroxyl
      radical-scavenging antioxidant and inhibitor of lipid peroxidation is presented. 

PMID- 23557728
TI  - The effects of two therapeutic patellofemoral taping techniques on strength,
      endurance, and pain responses.
AB  - OBJECTIVE: To compare the effects of taping techniques on clinical measures in
      patellofemoral pain syndrome (PFPS) patients. DESIGN: Crossover experimental
      design. SETTING: Controlled laboratory. PARTICIPANTS: Twenty physically active
      PFPS patients. MAIN OUTCOME MEASURES: Isokinetic strength and endurance, and
      perceived pain. RESULTS: Bilateral baseline differences existed for strength
      (involved = 1.8 +/- 0.5 Nm/kg; uninvolved = 2.1 +/- 0.5 Nm/kg; p = 0.001) and
      endurance (involved = 35.6 +/- 14.0 J/kg; uninvolved = 40.2 +/- 12.9 J/kg; p =
      0.013). Strength (McConnell = 2.1 +/- 0.6 Nm/kg, 95% SCI = (1.1, 4.2);
      Spider((r)) = 2.1 +/- 0.5 Nm/kg, 95% SCI = (0.9, 4.0)) and endurance (McConnell =
      42.9 +/- 13.8 J/kg, 95% SCI = (2.9, 11.6); Spider((r)) = 42.5 +/- 11.0 J/kg, 95%
      SCI = (2.6, -11.3)) increased when taped compared to baseline. Pain decreased
      during strength (baseline = 3.0 +/- 2.2 cm; McConnell = 1.9 +/- 1.7 cm, 95% SCI =
      (-1.8, -0.4); Spider((r)) = 1.6 +/- 2.0 cm, 95% SCI = (-2.0, -0.5)) and endurance
      (baseline = 2.5 +/- 2.0 cm; McConnell = 1.5 +/- 1.8 cm, 95% SCI = (-1.6, -0.4);
      Spider((r)) = 1.1 +/- 0.8 cm, 95% SCI = (-1.7, -0.5)) measurements when taped.
      Differences between taping techniques were insignificant. CONCLUSIONS: Taping
      improved clinical measures in PFPS patients. No differences existed between
      Spider((r)) and McConnell techniques.

PMID- 23557729
TI  - A systematic review of the factors influencing African Americans' participation
      in cancer clinical trials.
AB  - OBJECTIVE: This systematic review was conducted to synthesize the existing
      evidence regarding key considerations influencing African Americans'
      participation in cancer clinical trials (CCTs). METHODS: The PubMed and PsycINFO
      databases were searched to identify peer-reviewed publications during the last
      decade (2002-2011) that met our inclusionary criteria. Our search utilized
      Boolean combinations of the following terms: "clinical trial"; "cancer";
      "neoplasm"; "African American"; "Black"; "caregiver"; "decision making";
      "recruitment"; "companion"; "family"; "significant other"; and "social support".
      RESULTS: A total of 267 articles were identified in the database searches. Of
      these articles, a total of 31 were determined to meet the inclusion criteria and
      were retained for review. Key issues that emerged as impediments to a successful
      recruitment of African Americans to CCTs included negative attitudes towards
      clinical trials, low levels of knowledge and awareness regarding CCTs, religious
      beliefs, and structural barriers, such as transportation, childcare, and access
      to health care. Recommendations from physicians, family members, and friends may
      promote CCT participation. Multimedia, and culturally-appropriate recruitment
      approaches may also be effective in soliciting participation among African
      Americans. CONCLUSION: Existing research underscores the importance of social
      support from family and friends, cultural appropriateness and sensitivity from
      physicians and in the design of the CCT, and enhanced education among African
      Americans in decision-making processes. As African Americans are underrepresented
      in CCTs, targeted strategies to enhance recruitment efforts and improve cancer
      treatment outcomes are essential.

PMID- 23557730
TI  - The HealthyTexts study: a randomized controlled trial to improve skin cancer
      prevention behaviors among young people.
AB  - Several randomized trials have found behavior change programs delivered via text
      messaging to be efficacious to improve preventive health behaviors such as
      physical activity and stopping smoking; however few have assessed its value in
      skin cancer prevention or early detection. The HealthyTexts study enrolled 678
      participants 18-42 years, and assigned them to receive 21 text messages about
      skin cancer prevention, skin self-examination or physical activity (attention
      control) over the course of one year. Baseline data have been collected and
      outcomes will be assessed at three months and twelve months post-intervention.
      The trial aims to increase the mean overall sun protection habits index score
      from 2.3 to 2.7 with a standard deviation of 0.5 (effect size of 0.5) and the
      proportion of people who conduct a whole-body skin self-examination by an
      absolute 10%. This paper describes the study design and participants' baseline
      characteristics. In addition, participants' goals for their health, and
      strategies they apply to achieve those goals are summarized.

PMID- 23557731
TI  - Enhanced chemical stability of adomet analogues for improved methyltransferase
      directed labeling of DNA.
AB  - Methyltransferases catalyze specific transfers of methyl groups from the
      ubiquitous cofactor S-adenosyl-l-methionine (AdoMet) to various nucleophilic
      positions in biopolymers like DNA, RNA, and proteins. We had previously described
      synthesis and application of AdoMet analogues carrying sulfonium-bound 4
      substituted but-2-ynyl side chains for transfer by methyltransferases. Although
      useful in certain applications, these cofactor analogues exhibited short
      lifetimes in physiological buffers. Examination of the reaction kinetics and
      products showed that their fast inactivation followed a different pathway than
      observed for AdoMet and rather involved a pH-dependent addition of a water
      molecule to the side chain. This side reaction was eradicated by synthesis of a
      series of cofactor analogues in which the separation between an electronegative
      group and the triple bond was increased from one to three carbon units. The
      designed hex-2-ynyl moiety-based cofactor analogues with terminal amino, azide,
      or alkyne groups showed a markedly improved enzymatic transalkylation activity
      and proved well suitable for methyltransferase-directed sequence-specific
      labeling of DNA in vitro and in bacterial cell lysates. 

PMID- 23557732
TI  - Low-intensity far-red light inhibits early lesions that contribute to diabetic
      retinopathy: in vivo and in vitro.
AB  - PURPOSE: Treatment with light in the far-red to near-infrared region of the
      spectrum (photobiomodulation [PBM]) has beneficial effects in tissue injury. We
      investigated the therapeutic efficacy of 670-nm PBM in rodent and cultured cell
      models of diabetic retinopathy. METHODS: Studies were conducted in streptozotocin
      induced diabetic rats and in cultured retinal cells. Diabetes-induced retinal
      abnormalities were assessed functionally, biochemically, and histologically in
      vivo and in vitro. RESULTS: We observed beneficial effects of PBM on the neural
      and vascular elements of retina. Daily 670-nm PBM treatment (6 J/cm(2)) resulted
      in significant inhibition in the diabetes-induced death of retinal ganglion
      cells, as well as a 50% improvement of the ERG amplitude (photopic b wave
      responses) (both P < 0.01). To explore the mechanism for these beneficial
      effects, we examined physiologic and molecular changes related to cell survival,
      oxidative stress, and inflammation. PBM did not alter cytochrome oxidase activity
      in the retina or in cultured retinal cells. PBM inhibited diabetes-induced
      superoxide production and preserved MnSOD expression in vivo. Diabetes
      significantly increased both leukostasis and expression of ICAM-1, and PBM
      essentially prevented both of these abnormalities. In cultured retinal cells, 30
      mM glucose exposure increased superoxide production, inflammatory biomarker
      expression, and cell death. PBM inhibited all of these abnormalities.
      CONCLUSIONS: PBM ameliorated lesions of diabetic retinopathy in vivo and reduced
      oxidative stress and cell death in vitro. PBM has been documented to have minimal
      risk. PBM is noninvasive, inexpensive, and easy to administer. We conclude that
      PBM is a simple adjunct therapy to attenuate the development of diabetic
      retinopathy.

PMID- 23557733
TI  - Comparative phospholipid profiles of control and glaucomatous human trabecular
      meshwork.
AB  - PURPOSE: We compared phospholipid (phosphatidylcholine, phosphatidylserine,
      phosphatidylethanolamine, and phosphatidylinositol) profiles of control and
      glaucomatous trabecular meshwork (TM) derived from human donors. METHODS: Control
      TM and most primary open angle glaucoma (POAG) TM were collected from cadaver
      donors. A select subset of POAG surgical TM samples also were collected for
      analyses. Lipid extraction was performed using a modification of the Bligh and
      Dyer method, protein concentrations were determined using the Bradford method,
      and for select samples confirmed with densitometry of PHAST gels. Lipids were
      identified and subjected to ratiometric quantification using a TSQ quantum Access
      Max triple quadrupole mass spectrometer with precursor ion scan (PIS) or neutral
      ion loss scan (NLS), using appropriate class specific lipid standards. RESULTS:
      The comparative profiles of phosphatidylcholine, phosphatidylserine,
      phosphoethanolamine, and phosphatidylinositol between control and glaucomatous TM
      showed several species common between them. A number of unique lipids in all four
      phospholipid classes also were identified in control TM that were absent in
      glaucoma TM and vice versa. CONCLUSIONS: A number of phospholipids were found to
      be uniquely present in control but absent in glaucomatous TM and vice versa.
      Compared to a previous study of control and POAG blood, a number of these
      phospholipids are absent locally (TM), as well as systemically (in blood).

PMID- 23557734
TI  - Abeta-induced senescent retinal pigment epithelial cells create a proinflammatory
      microenvironment in AMD.
AB  - PURPOSE: Chronic inflammation is implicated in the pathogenesis of AMD. The
      source of chronic inflammation is often attributed to the progressive activation
      of immune cells over time. However, recent studies have shown that senescent
      cells can alter tissue microenvironment via secretion of growth factors,
      proteases, and inflammatory cytokines and might be an additional source of
      chronic inflammation. We hypothesized that altered secretory pattern in Abeta
      induced senescent RPE cells may contribute to compromised RPE barrier integrity
      and chronic inflammation in AMD. METHODS: Senescence was assessed by measuring
      the SA-beta-Galactosidase activity, the expressions of p16(INK4a) and ATM, and
      cell cycle analysis. Expressions of IL-8 and MMPs were analyzed by RT-PCR, ELISA,
      and gelatin zymography. The barrier structures of RPE cells were detected by
      actin-tracker, ZO-1, claudin-19, occludin immunochemistry, and Western blot;
      barrier function was analyzed by measuring transepithelial resistance (TER) and
      transepithelial diffusion rate of FITC-dextran. For inhibitory studies, MMP-9 was
      inhibited by RNA interference strategy. RESULTS: Abeta promotes RPE cells to
      enter senescence and secrete higher concentrations of IL-8 and MMP-9. Secretion
      of MMP-9 is associated with compromised barrier integrity and with processing of
      IL-8 to a more activated form. Silence of MMP-9 preserved the barrier integrity
      of senescent RPE cells. CONCLUSIONS: The altered secretory phenotype of senescent
      RPE cells may contribute to age-related inflammation in AMD. Chinese Abstract.

PMID- 23557735
TI  - Impaired speed perception but intact luminance contrast perception in people with
      one eye.
AB  - PURPOSE: It is generally accepted that early visual deprivation from monocular
      enucleation (ME; the surgical removal of one eye) results in intact spatial
      vision. Yet, motion perception studies in this population yield inconsistent
      findings. Here, we investigated speed and luminance contrast perception in a
      group of ME individuals. METHODS: Twelve ME participants (mean age = 24 years;
      mean age at enucleation = 24 months) and 17 controls (mean age = 25 years)
      viewing binocularly (BV) and monocularly (MV) completed a series of speed
      discrimination and luminance contrast detection and discrimination tasks. Stimuli
      consisted of 0.5 cpd vertical sine wave gratings varying in speed (3.8 degrees /s
      24 degrees /s) or luminance contrast (0%-78%). A second set of luminance contrast
      tasks with 4 cpd gratings teased apart any spatial frequency effects. RESULTS:
      The ME group exhibited elevated speed discrimination thresholds compared with BV
      (P = 0.001) and MV (P = 0.027) controls, but intact luminance contrast
      discrimination (P = 0.530). Notably, both ME and MV groups displayed elevated
      luminance contrast detection thresholds compared with the BV group (Ps <= 0.006).
      However, the ME group exhibited slightly lower thresholds compared with MV
      controls for all 4 cpd tasks. CONCLUSIONS: Our data indicate a disruption in the
      development of speed perception, but not luminance contrast perception with
      monocular enucleation. These data highlight the importance of receiving healthy
      binocular vision during postnatal development for the maturation of cortical
      regions associated with motion processing.

PMID- 23557737
TI  - Lectin microarray profiling and relative quantification of glycome associated
      with proteins of neonatal wt and rd1 mice retinae.
AB  - PURPOSE: Progressive dynamic, relative quantitative changes were compared in
      glycans associated with retinal proteins of wild type (wt) and retinal
      degeneration 1 (rd1) mice during neonatal development and degeneration of
      retinae. METHODS: Proteins extracted from retinae of postnatal days 2 (PN2), PN7,
      and PN14 wt and rd1 mice were labeled with Cy3-fluorescent dye. Glycome of these
      proteins was quantified relatively by lectin microarray technique. Net
      fluorescence emitted by individual complexes formed between 45 lectins and Cy3
      labeled proteins was measured by evanescent-field fluorescence-assisted
      microarray reader. RESULTS: GlcNAcbeta1-oligomer and high-mannose/Manalpha1-6Man
      were major glycans associated with the proteins of PN2, PN7, and PN14 wt and rd1
      mice retinae. Gal/GalNAc/Man3-core-bi-/tri-antennary-complex, Sia2-3Galbeta1
      4GlcNAc, and high-mannose glycans were conjugated mainly to proteins from PN7 rd1
      and PN14 wt retinae, respectively. With increasing neonatal age, mannosylated,
      GlcNAcbeta, and sialylated (minor component) glycans were increased, and
      fucosylated GlcNAc/Galbeta glycans were decreased significantly in wt retinal
      proteins. This trend was less evident in PN14 rd1 retinal proteins. Mouse retina
      was almost devoid of Siaalpha2-6 (except WGA bound Sia), Fucalpha1-2, and
      Gal/GalNAc-containing glycans. STL reacting GlcNAc oligomers were high in PN2 rd1
      retinae. CONCLUSIONS: Quantitative dynamic, relative variation in high-mannose
      and GlcNAc glycans, Siaalpha2-3Galbeta1-4GlcNAc associated with proteins from
      PN2, PN7, and PN14 wt and rd1 mice retinae suggested that these glycans
      participate in retinal development and degeneration, and may be used as markers
      for retinal electrophysiologic integrity during transplantation/therapy studies;
      Siaalpha2-3Galbeta1-4GlcNAc-specific Agrocybe cylindracea lectin and other
      lectins may be used to enrich/purify retinal ribbon synapse glycoproteins and
      other glycoproteins including rhodopsin. Further investigations are required.

PMID- 23557736
TI  - Negative lens-induced myopia in infant monkeys: effects of high ambient lighting.
AB  - PURPOSE: To determine whether high light levels, which have a protective effect
      against form-deprivation myopia, also retard the development of lens-induced
      myopia in primates. METHODS: Hyperopic defocus was imposed on 27 monkeys by
      securing -3 diopter (D) lenses in front of one eye. The lens-rearing procedures
      were initiated at 24 days of age and continued for periods ranging from 50 to 123
      days. Fifteen of the treated monkeys were exposed to normal laboratory light
      levels (~350 lux). For the other 12 lens-reared monkeys, auxiliary lighting
      increased the illuminance to 25,000 lux for 6 hours during the middle of the
      daily 12 hour light cycle. Refractive development, corneal power, and axial
      dimensions were assessed by retinoscopy, keratometry, and ultrasonography,
      respectively. Data were also obtained from 37 control monkeys, four of which were
      exposed to high ambient lighting. RESULTS: in normal- and high-light-reared
      monkeys, hyperopic defocus accelerated vitreous chamber elongation and produced
      myopic shifts in refractive error. the high light regimen did not alter the
      degree of myopia (high light: -1.69 +/- 0.84 D versus normal light: -2.08 +/-
      1.12 D; P = 0.40) or the rate at which the treated eyes compensated for the
      imposed defocus. Following lens removal, the high light monkeys recovered from
      the induced myopia. The recovery process was not affected by the high lighting
      regimen. CONCLUSIONS: In contrast to the protective effects that high ambient
      lighting has against form-deprivation myopia, high artificial lighting did not
      alter the course of compensation to imposed defocus. These results indicate that
      the mechanisms responsible for form-deprivation myopia and lens-induced myopia
      are not identical.

PMID- 23557738
TI  - Two-photon microscopy and fluorescence lifetime imaging of retinal pigment
      epithelial cells under oxidative stress.
AB  - PURPOSE: The aim of this study was to investigate the autofluorescence (AF) of
      the RPE with two-photon microscopy (TPM) and fluorescence lifetime imaging (FLIM)
      under normal and oxidative stress conditions. METHODS: Porcine RPE-choroid
      explants were used for investigation. The RPE-choroid tissue was preserved in a
      perfusion organ culture system. Oxidative stress was induced by laser
      photocoagulation with frequency-doubled ND:YAG laser (532 nm) and by exposure to
      different concentrations (0, 1, 10 mM) of ferrous sulfate (FeSO4) for 1 hour. At
      indicated time points after exposure, the tissue was examined with TPM and FLIM.
      Intracellular reactive oxygen species around the photocoagulation lesion were
      detected with chloromethyl-2'7'-dichlorofluorescein diacetate (CM-H2DCFDA).
      Melanosomes were isolated from RPE cells and their fluorescence properties were
      investigated under normal and oxidized conditions. RESULTS: Under normal
      conditions, AF in RPE cells with TPM is mostly originated from melanosomes, which
      has a very short fluorescence lifetime (FLT; mean = 117 ps). Under oxidative
      stress induced by laser irradiation and FeSO4 exposure, bright granular AF
      appears inside and around RPE cells, whose FLT is significantly longer (mean =
      1388 ps) than the FLT of the melanosome-AF. Excitation and emission peaks are
      found at 710 to 750 nm and 450 to 500 nm, respectively. Oxidative stress
      increases the fluorescence intensity of the melanosomes but does not change their
      FLT. CONCLUSIONS: TPM reveals acute oxidative stress-induced bright AF granules
      inside and around RPE cells which can be clearly discriminated from melanosomes
      by FLIM. TPM combined with FLIM is a useful tool of live-cell analysis to
      investigate functional alterations of the RPE.

PMID- 23557739
TI  - A genetic variant in the SKIV2L gene is significantly associated with age-related
      macular degeneration in a Han Chinese population.
AB  - PURPOSE: Previous studies have shown that genetic variants in the complement
      component 2 (C2)/complement factor B (BF) gene are associated with AMD in
      Caucasians, but not in Han Chinese. Recent studies have indicated that genetic
      variants in the neighboring superkiller viralicidic activity 2-like (SKIV2L) gene
      showed significant association with AMD. We conducted this study to investigate
      whether genetic variants in the SKIV2L gene are associated with AMD in a Han
      Chinese population. METHODS: Thirteen single nucleotide polymorphisms (SNPs) in
      the C2-BF-RDBP-SKIV2L-STK19 region were genotyped by the SNaPshot method in a
      cohort composed of 449 patients with choriodal neovascularization (CNV) AMD and
      1025 healthy controls of Han Chinese descent. RESULTS: Among the SNPs genotyped,
      P values of seven SNPs were less than 0.05; however, only rs429608 was found to
      be significantly associated with AMD after correction for multiple testing. The
      minor allele (A) frequency of rs429608 was 0.050 in cases and 0.089 in controls,
      and the P value was 3.76 * 10(-4) (0.00489 after Bonferroni correction), with an
      odds ratio of 0.55 (95% confidence interval, 0.40-0.77). The SKIV2L gene was
      expressed in the human RPE, retina, and D407 (human RPE) cells, and in mouse
      retinas and RPE. CONCLUSIONS: We demonstrated that the rs429608 genetic variant
      in the SKIV2L gene was significantly associated with AMD in a Han Chinese
      population. SKIV2L may play an important role in the development of AMD.

PMID- 23557740
TI  - Protective effect of pioglitazone on retinal ischemia/reperfusion injury in rats.
AB  - PURPOSE: To investigate the protective effect of pioglitazone on the rat retina
      after ischemia/reperfusion (I/R) injury and to explore its possible mechanisms.
      METHODS: Retinal ischemia was induced by increasing the intraocular pressure to
      110 mm Hg for 60 minutes, and pioglitazone was delivered 3 hours before the I/R.
      Retinal damage was quantified by measuring the thickness of the retina, the
      functional changes of visual evoked potential (VEP) and electroretinography
      (ERG), and the number of retinal ganglion cells (RGCs) at 7 days after I/R
      injury. Real-time PCR and Western blot analysis were performed to measure the
      glial fibrillary acidic protein (GFAP) expression. Retinal cell apoptosis was
      detected by TUNEL assay at 24 hours after reperfusion. Nuclear factor-kappaB (NF
      kappaB), Bax, and Bcl-2 in the retina were determined by Western blot analysis.
      RESULTS: The I/R produced a degenerative effect primarily in the ganglion cell
      layer, inner plexiform layer, and inner nuclear layer. Pioglitazone maintained
      the retinal thickness, promoted the survival of RGCs, and attenuated the
      destruction of ERG and VEP caused by I/R. Pioglitazone pretreatment also
      suppressed NF-kappaB activation and altered GFAP overexpression. The number of
      TUNEL-labeled cells significantly decreased in the retinas pretreated with
      pioglitazone, and the Bax-Bcl-2 ratio was much lower in the retinas pretreated
      with pioglitazone than in the I/R group. CONCLUSIONS: Pioglitazone could inhibit
      activation of the glia cells, prevent cell apoptosis, and protect the retina from
      subsequent cellular damage caused by the retinal I/R. The possible mechanism
      might involve the NF-kappaB pathway.

PMID- 23557741
TI  - Targeted expression of anoctamin calcium-activated chloride channels in rod
      photoreceptor terminals of the rodent retina.
AB  - PURPOSE: In the vertebrate retina, calcium-activated chloride channels are
      expressed in photoreceptor synaptic terminals. These channels are involved in the
      control of transmitter release in the dark. The search for their molecular
      identity has recently lead to the localization of the protein anoctamin 2 (also
      TMEM16B) in the outer plexiform layer of the rodent retina. Since both rod and
      cone photoreceptors have their terminals in this layer, it was not clear which of
      these express anoctamin 2. Here, we examine rod spherules and cone pedicles for
      expression of anoctamin 2. METHODS: Expression of anoctamin genes was studied in
      the rat eye using RT-PCR. Immunohistochemical experiments were used to localize
      anoctamins and chloride transporters with their regulatory kinases. Photoreceptor
      synaptic proteins, as well as the lectins Peanut agglutinin and Griffonia
      simplicifolia agglutinin, were used to distinguish retinal structures. RESULTS:
      Anoctamin 1, 2, and 10 were found to be expressed in the eye. Anoctamin 2 was
      expressed as a splice variant that includes exon 15 of the genomic structure. The
      protein is exclusively expressed in rod terminals and is not present in cone
      pedicles. Expression is not clustered at the ribbon complex, but spread across
      the presynaptic membrane where it colocalizes with the plasma membrane calcium
      pump. The electroneutral chloride transporter NKCC1 is expressed in photoreceptor
      terminals, together with its regulatory kinases SPAK and OSR1. CONCLUSIONS: Rod
      photoreceptor terminals possess the molecular machinery for chloride accumulation
      and for the generation of calcium-dependent chloride currents conducted through
      anoctamin 2 channels. We discuss this finding in the framework of the established
      hypothesis that calcium-activated chloride channels are part of a feedback
      inhibition mechanism that limits transmitter release in the dark.

PMID- 23557742
TI  - Modified monovision with spherical aberration to improve presbyopic through-focus
      visual performance.
AB  - PURPOSE: To investigate the impact on visual performance of modifying monovision
      with monocularly induced spherical aberration (SA) to increase depth of focus
      (DoF), thereby enhancing binocular through-focus visual performance. METHODS: A
      binocular adaptive optics (AO) vision simulator was used to correct both eyes'
      native aberrations and induce traditional (TMV) and modified (MMV) monovision
      corrections. TMV was simulated with 1.5 diopters (D) of anisometropia (dominant
      eye at distance, nondominant eye at near). Zernike primary SA was induced in the
      nondominant eye in MMV. A total of four MMV conditions were tested with various
      amounts of SA (+/- 0.2 and +/- 0.4 MUm) and fixed anisometropia (1.5 D).
      Monocular and binocular visual acuity (VA) and contrast sensitivity (CS) at 10
      cyc/deg and binocular summation were measured through-focus in three cyclopledged
      subjects with 4-mm pupils. RESULTS: MMV with positive SA had a larger benefit for
      intermediate distances (1.5 lines at 1.0 D) than with negative SA, compared with
      TMV. Negative SA had a stronger benefit in VA at near. DoF of all MMV conditions
      was 3.5 +/- 0.5 D (mean) as compared with TMV (2.7 +/- 0.3 D). Through-focus CS
      at 10 cyc/deg was significantly reduced with MMV as compared to TMV only at
      intermediate object distances, however was unaffected at distance. Binocular
      summation was absent at all object distances except 0.5 D, where it improved in
      MMV by 19% over TMV. CONCLUSIONS: Modified monovision with SA improves through
      focus VA and DoF as compared with traditional monovision. Binocular summation
      also increased as interocular similarity of image quality increased due to
      extended monocular DoF.

PMID- 23557743
TI  - DNA-PK phosphorylation of IGFBP-3 is required to prevent apoptosis in retinal
      endothelial cells cultured in high glucose.
AB  - PURPOSE: The goal of this study was to determine whether Compound 49b stimulates
      insulin-like growth factor binding protein-3 (IGFBP-3) activation in retinal
      endothelial cells (REC) through DNA-dependent protein kinase (DNA-PK). METHODS:
      REC were grown in a normal glucose (5 mM) or high glucose medium (25 mM). Some
      cells were transfected with protein kinase A (PKA) siRNA, following treatment
      with 50 nM Compound 49b, a novel beta-adrenergic receptor agonist. Cell proteins
      were extracted and analyzed for DNA-PK expression by Western blotting. Additional
      cells were treated with or without NU7441 (a specific DNA-PK inhibitor) prior to
      Compound 49b treatment. Cell lysates were processed for IGFBP-3 ELISA analyses
      and Western blotting to measure casein kinase 2 (CK2). Immunoprecipitation for
      total and phospho-IGFBP-3, cell proliferation and cell death measurements were
      done after transfection with the S(156)A IGFBP-3 mutation (key phosphorylation
      site involved in DNA-PK) plasmid DNA. RESULTS: Compound 49b required DNA-PK to
      activate IGFBP-3 in REC. IGFBP-3 activation was significantly reduced following
      treatment with either the DNA-PK inhibitor or following transfection with the
      IGFBP-3 S(156)A mutant plasmid (P < 0.05). Significant increases in cell death
      and decreases in cell proliferation were also observed in cells transfected with
      the IGFBP-3 S(156)A mutant plasmid (P < 0.05). Casein kinase levels were not
      altered after treatment with NU7741 or Compound 49b. CONCLUSIONS: Our findings
      suggest Compound 49b induces DNA-PK levels through PKA activity. DNA-PK is
      required for Compound 49b-induced IGFBP-3 expression, leading to inhibition of
      REC cell death.

PMID- 23557745
TI  - Association of the chromosome 11q13.5 variant with atopic dermatitis in Austrian
      patients.
AB  - BACKGROUND: Recently, the two single nucleotide polymorphisms, rs7927894 on
      chromosome 11q13.5 and rs877776 within the region of the hornerin gene, were
      identified as novel susceptibility variants for atopic dermatitis in the first
      genome wide association study in atopic dermatitis. OBJECTIVE: The aim of our
      study was to evaluate the influence of these two genetic variants on atopic
      dermatitis and disease-related phenotypes in the Austrian population. METHODS:
      275 atopic dermatitis patients and 243 controls were genotyped for the two
      variants rs7927894 and rs877776 by using Taqman based allelic discrimination
      assays. RESULTS: When comparing patients with controls we found a significant
      association of the rs7927894 variant on chromosome 11q13.5 with atopic dermatitis
      (OR: 1.71; CI 1.14-2.59; p=0.010). Subgroup analysis revealed no significant
      association of rs7927894 with early age of onset of the disease, concomitant
      asthma and allergic rhinoconjunctivitis, total serum IgE levels and family
      history of atopy. The analysis of the rs877776 variant showed neither a relevant
      difference in the allelic distribution between patients and controls nor a
      statistically significant association with any of the analyzed atopic dermatitis
      phenotypes. CONCLUSIONS: In summary our data show a statistically significant
      association of the rs7927894 variant on chromosome 11q13.5 with atopic dermatitis
      but not with other disease-related phenotypes. Therefore, we assume that the
      rs7927894 single nucleotide polymorphism selectively influences eczema
      development. More investigations in distinct study populations are needed to
      assess the role of this interesting polymorphism in atopic dermatitis.

PMID- 23557744
TI  - The relationship between cup-to-disc ratio and estimated number of retinal
      ganglion cells.
AB  - PURPOSE: To investigate the relationship between cup-to-disc ratio (CDR) and
      estimates of retinal ganglion cell (RGC) number. METHODS: This cross-sectional
      study included 156 healthy eyes, 53 glaucoma suspects, and 127 eyes with
      glaucoma. All eyes had standard automated perimetry (SAP), Cirrus SD-OCT, and
      stereoscopic optic disc photography within 6 months. CDR was determined from
      stereoscopic photographs by two or more masked graders. The number of RGCs in
      each eye was estimated using a published model that combines estimates of RGC
      number from SAP sensitivity thresholds and SD-OCT retinal nerve fiber layer
      measurements. RESULTS: The mean estimated RGC count was 1,063,809 in healthy
      eyes; 828,522 in eyes with suspected glaucoma; and 774,200 in early, 468,568 in
      moderate, and 218,471 in advanced glaucoma. Healthy eyes had a mean vertical CDR
      of 0.45 +/- 0.15 vs. 0.80 +/- 0.16 in glaucomatous eyes. There was good
      correlation between stereophotographic vertical CDR and SD-OCT vertical CDR (R(2)
      = 0.825; P < 0.001). The relationship between estimated RGCs and vertical CDR was
      best represented using a third degree polynomial regression model, including age
      and optic disc area, which accounted for 83.3% of the variation in estimated RGC
      counts. The nonlinear relationship between RGC estimates and CDRs indicated that
      eyes with a large CDR would require loss of large RGC numbers for a small
      increase in CDR. CONCLUSIONS: The relationship between estimated RGC counts and
      CDR suggests that assessment of change in CDR is an insensitive method for
      evaluation of progressive neural losses in glaucoma. Even relatively small
      changes in CDR may be associated with large losses of RGCs, especially in eyes
      with large CDRs. (ClinicalTrials.gov numbers, NCT00221923, NCT00221897.).

PMID- 23557746
TI  - Application of target-mediated drug disposition model to small molecule heat
      shock protein 90 inhibitors.
AB  - Replacement of hydrogen with fluorine within three pairs of structurally similar
      small molecule inhibitors of heat shock protein 90 (HSP90) resulted in
      differences in inhibition constants (K(i)) in vitro as well as marked differences
      in rat intravenous pharmacokinetic profiles. The difference in pharmacokinetic
      profiles between lower and higher affinity inhibitors (LAIs and HAIs,
      respectively) was characterized by remarkably different estimates for steady
      state volumes of distribution (V(ss): 1.8-2.0 versus 10-13 l/kg) with comparable
      clearance estimates (3.2-3.5 l/h per kilogram). When the observed V(ss) estimates
      were compared with the values predicted with the tissue-composition-based model,
      the observed V(ss) estimates for HAIs were 4- to 8-fold larger than the predicted
      values, whereas the V(ss) values for LAIs were comparable. Accordingly, a
      negative relationship between in vitro HSP90 K(i) versus in vivo V(ss) estimates
      was observed among these inhibitors. We therefore hypothesized that
      pharmacokinetic profiles of these inhibitors could be characterized by a target
      mediated drug disposition (TMDD) model. In vivo equilibrium dissociation constant
      (K(D)) estimates for HAIs due to target binding by TMDD model with rapid binding
      approximation were 1-6 nM (equivalent to 0.3-2 nM free drug), which appeared
      comparable to the in vitro K(i) estimates (2-3 nM). In vivo KD values of LAIs
      were not accurately determined by the TMDD model, likely due to nonspecific
      binding-dependent tissue distribution obscuring TMDD profiles. Overall, these
      results suggest that the observed large Vss estimates for potent HSP90 inhibitors
      are likely due to pharmacological target binding.

PMID- 23557747
TI  - Does throbbing pain have a brain signature?
AB  - Pain sometimes has a throbbing, pulsating quality, particularly when it is severe
      and disabling. We recently challenged the presumption that this throbbing quality
      is a sensory experience of arterial pulsations, but were unable to offer an
      alternative explanation for its rhythmic character. Here we report a case study
      of a woman with a history of daily headache consistent with the diagnosis of
      chronic migraine, but whose throbbing quality persisted long after the resolution
      of the headache. This chronic, daily, and persistent throbbing sensation, in the
      absence of headache pain, prompted closer examination for its neurophysiological
      correlate. By simultaneously recording the subjective report of the throbbing
      rhythm, arterial pulse, and high-density electroencephalogram, we found that the
      subjective throbbing rate (48+/-1.7beats per minute) and heart rate (68+/-2beats
      per minute) were distinct, in accord with our previous observations that the 2
      are unrelated. On spectral analysis of the electroencephalogram, we found that
      the overall amount of activity in the alpha range (8 to 12Hz), or alpha power,
      increased in association with greater throbbing intensity. In addition, we also
      found that the rhythmic oscillations of overall alpha power, the so-called
      modulations of alpha power, coincided with the timing of the throbbing rhythm,
      and that this synchrony, or coherence, was proportional to the subjective
      intensity of the throbbing quality. This index case will motivate further studies
      whose aim is to determine whether modulations of alpha power could more generally
      represent a neurophysiological correlate of the throbbing quality of pain.

PMID- 23557748
TI  - Acute ST-elevation myocardial infarction in patients hospitalized for noncardiac
      conditions.
AB  - BACKGROUND: Major advances have been made in the treatment of ST-elevation
      myocardial infarction (STEMI) in outpatients. In contrast, little is known about
      outcomes in STEMI that occur in patients hospitalized for a noncardiac condition.
      METHODS AND RESULTS: This was a retrospective, single-center study of inpatient
      STEMIs from January 1, 2007, to July 31, 2011. Forty-eight cases were confirmed
      to be inpatient STEMIs of a total of 139 410 adult discharges. These patients
      were older and more often female and had higher rates of chronic kidney disease
      and prior cerebrovascular events compared with 227 patients with outpatient
      STEMIs treated during the same period. Onset of inpatient STEMI was heralded most
      frequently by a change in clinical status (60%) and less commonly by patient
      complaints (33%) or changes on telemetry. Coronary angiography and percutaneous
      coronary intervention were performed in 71% and 56% of patients, respectively.
      The median time to obtain ECG (41 [10, 600] versus 5 [2, 10] minutes; P<0.001),
      ECG to angiography time (91 [26, 209] versus 35 [25, 46] minutes; P<0.001) and
      ECG to first device activation (FDA) (129 [65, 25] versus 60 [47, 76] minutes;
      P<0.001) were longer for inpatient versus outpatient STEMI. Survival to discharge
      was lower for inpatient STEMI (60% versus 96%; P<0.001), and this difference
      persisted after adjusting for potential confounders. CONCLUSIONS: Patients who
      develop a STEMI while hospitalized for a noncardiac condition are older and more
      often female, have more comorbidities, have longer ECG-to-FDA times, and are less
      likely to survive than patients with an outpatient STEMI.

PMID- 23557749
TI  - Psoriasis and major adverse cardiovascular events: a systematic review and meta
      analysis of observational studies.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease that may be associated
      with increased risk of cardiovascular events, including cardiovascular mortality,
      myocardial infarction, and stroke. METHODS AND RESULTS: We searched the MEDLINE,
      EMBASE, and Cochrane Central Register databases for relevant studies in English
      between January 1, 1980, and January 1, 2012. Extraction was by 3 independent
      reviewers. Summary incidence, risk ratios (RRs), and confidence intervals (CIs)
      were calculated using fixed-effects and random-effects modeling. Meta-regression
      was also performed to identify sources of between-study variation. Nine studies
      were included, representing a total of 201 239 patients with mild and 17 415
      patients with severe psoriasis. The level of covariate adjustment varied among
      studies, leading to the possibility of residual confounding. Using the available
      adjusted effect sizes, mild psoriasis remained associated with a significantly
      increased risk of myocardial infarction (RR, 1.29; 95% CI, 1.02 to 1.63) and
      stroke (RR, 1.12; 95% CI, 1.08 to 1.16). Severe psoriasis was associated with a
      significantly increased risk of cardiovascular mortality (RR, 1.39; 95% CI, 1.11
      to 1.74), myocardial infarction (RR, 1.70; 95% CI, 1.32 to 2.18), and stroke (RR,
      1.56 95% CI, 1.32 to 1.84). Based on these risk ratios and the background
      population event rates, psoriasis is associated with an estimated excess of 11
      500 (95% CI, 1169 to 24 407) major adverse cardiovascular events each year.
      CONCLUSIONS: Mild and severe psoriasis are associated with an increased risk of
      myocardial infarction and stroke. Severe psoriasis is also associated with an
      increased risk of cardiovascular mortality. Future studies should include more
      complete covariate adjustment and characterization of psoriasis severity.

PMID- 23557750
TI  - Enhanced lipid peroxidation and platelet activation as potential contributors to
      increased cardiovascular risk in the low-HDL phenotype.
AB  - BACKGROUND: Low high-density lipoprotein (HDL) levels are major predictors of
      cardiovascular (CV) events, even in patients on statin treatment with low-density
      lipoprotein (LDL) at target. In animal models HDLs protect LDL from oxidation and
      blunt platelet activation. Our study aimed to examine whether HDL levels are
      related to in vivo oxidative stress and platelet activation, as determinants of
      atherothrombosis. METHODS AND RESULTS: Urinary 8-iso-PGF2alpha and 11-dehydro
      TXB2, in vivo markers of oxidative stress and platelet activation, respectively,
      were measured in 65 coronary heart disease (CHD) normocholesterolemic patients
      with HDL <=35 mg/dL, and in 47 CHD patients with HDL >35 mg/dL. The 2 eicosanoids
      were also measured before and after an intensive exercise program in sedentary
      people (n=18) and before and after fenofibrate treatment in otherwise healthy
      subjects with low HDL (n=10). Patients with HDL <=35 mg/dL showed significantly
      higher urinary 8-iso-PGF2alpha (median [25th to 75th percentiles]: 289 [189 to
      380] versus 216 [171 to 321] pg/mg creatinine, P=0.019) and 11-dehydro-TXB2 (563
      [421 to 767] versus 372 [249 to 465] pg/mg creatinine, P=0.0001) than patients
      with higher HDL. A direct correlation was found between urinary 8-iso-PGF2alpha
      and 11-dehydro-TXB2 in the entire group of patients (rho=0.77, P<0.0001). HDL
      levels were inversely related to both 8-iso-PGF2alpha (rho=-0.32, P=0.001) and 11
      dehydro-TXB2 (rho=-0.52, P<0.0001). On multiple regression, only 8-iso-PGF2alpha
      (beta=0.68, P<0.0001) and HDL level (beta=-0.29, P<0.0001) were associated with
      urinary 11-dehydro-TXB2 excretion, independent of sex, age, smoking,
      hypertension, diabetes, previous myocardial infarction, total cholesterol, LDL,
      and triglycerides. Both intensive exercise and fenofibrate treatment
      significantly reduced the 2 eicosanoids in healthy subjects, in parallel with an
      HDL increase. CONCLUSIONS: A low HDL phenotype, both in CHD patients and in
      healthy subjects, is associated with increased lipid peroxidation and platelet
      activation. These data provide novel insight into the mechanisms linking low HDL
      with increased CV risk.

PMID- 23557752
TI  - When in rome, do like the Romans: certifying stroke centers with the rod of
      aesculapius or the medical caduceus of hermes?

PMID- 23557751
TI  - Diminished antioxidant activity of high-density lipoprotein-associated proteins
      in chronic kidney disease.
AB  - BACKGROUND: Decreased serum arylesterase activity, catalyzed by the high-density
      lipoprotein-associated paraoxonase (PON)-1, is associated with increased oxidant
      stress and atherosclerosis risk. We sought to determine the prognostic value of
      serum PON-1 activity, as monitored by PON or arylesterase activities, in subjects
      with chronic kidney disease (CKD), particularly in relation to established
      cardiac biomarkers. METHODS AND RESULTS: Serum arylesterase and PON activities
      were measured in sequential subjects with CKD (n=630; estimated glomerular
      filtration rate [eGFR] <60 mL/min per 1.73 m(2)) and an age- and sex-matched
      control group of non-CKD subjects (n=315) presenting for cardiac evaluations and
      prospectively followed for incident (3-year) major adverse cardiac events
      (composite of death, nonfatal myocardial infarction, and stroke). Serum
      arylesterase activity in CKD subjects was lower compared with that in non-CKD
      control subjects [median (interquartile range) 94 (77 to 112) versus 103 (85 to
      121) MUmol(L.min) per mL, P<0.001]; similarly, PON activity in CKD subjects was
      lower compared with that in non-CKD control subjects [median (interquartile
      range) 474 (275 to 936) versus 586 (301 to 1118) nmol(L.min) per mL, P<0.001].
      Lower serum arylesterase (hazard ratio 1.8, 95% CI 1.26 to 2.57, P<0.01) was a
      predictor of poorer outcomes. After adjusting for traditional risk factors and
      medication use, lower serum arylesterase (hazard ratio 1.55, 95% CI 1.08 to 2.23,
      P<0.05) still conferred an increased risk of major adverse cardiac events at 3
      years. CONCLUSIONS: In patients with CKD, decreased serum arylesterase activity,
      a measure of diminished antioxidant properties of PON-1, predicts higher risk of
      incident long-term adverse cardiovascular events (heart attack, stroke, or death)
      in multivariable models adjusting for established clinical and biochemical risk
      factors.

PMID- 23557753
TI  - Spatial transcriptional profile of the chick and mouse endocardial cushions
      identify novel regulators of endocardial EMT in vitro.
AB  - Valvular Interstitial Cells (VICs) are a common substrate for congenital and
      adult heart disease yet the signaling mechanisms governing their formation during
      early valvulogenesis are incompletely understood. We developed an unbiased
      strategy to identify genes important in endocardial epithelial-to-mesenchymal
      transformation (EMT) using a spatial transcriptional profile. Endocardial cells
      overlaying the cushions of the atrioventricular canal (AVC) and outflow tract
      (OFT) undergo an EMT to yield VICs. RNA sequencing (RNA-seq) analysis of gene
      expression between AVC, OFT, and ventricles (VEN) isolated from chick and mouse
      embryos at comparable stages of development (chick HH18; mouse E11.0) was
      performed. EMT occurs in the AVC and OFT cushions, but not VEN at this time. 198
      genes in the chick (n=1) and 105 genes in the mouse (n=2) were enriched 2-fold in
      the cushions. Gene regulatory networks (GRN) generated from cushion-enriched gene
      lists confirmed TGFbeta as a nodal point and identified NF-kappaB as a potential
      node. To reveal previously unrecognized regulators of EMT four candidate genes,
      Hapln1, Id1, Foxp2, and Meis2, and a candidate pathway, NF-kappaB, were selected.
      In vivo spatial expression of each gene was confirmed by in situ hybridization
      and a functional role for each in endocardial EMT was determined by siRNA
      knockdown in a collagen gel assay. Our spatial-transcriptional profiling strategy
      yielded gene lists which reflected the known biology of the system. Further
      analysis accurately identified and validated previously unrecognized novel
      candidate genes and the NF-kappaB pathway as regulators of endocardial cell EMT
      in vitro.

PMID- 23557755
TI  - Nursing strategies for Neuro PROTECT-ION.

PMID- 23557754
TI  - Channelopathies from mutations in the cardiac sodium channel protein complex.
AB  - The cardiac sodium current underlies excitability in heart, and inherited
      abnormalities of the proteins regulating and conducting this current cause
      inherited arrhythmia syndromes. This review focuses on inherited mutations in non
      pore forming proteins of sodium channel complexes that cause cardiac arrhythmia,
      and the deduced mechanisms by which they affect function and dysfunction of the
      cardiac sodium current. Defining the structure and function of these complexes
      and how they are regulated will contribute to understanding the possible roles
      for this complex in normal and abnormal physiology and homeostasis. This article
      is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". 

PMID- 23557756
TI  - Altered circulating levels of matrix metalloproteinases 2 and 9 and their
      inhibitors and effect of progesterone supplementation in women with endometriosis
      undergoing in vitro fertilization.
AB  - OBJECTIVE: To investigate differences in the activity of matrix
      metalloproteinases (MMPs) 2 and 9 and their respective tissue inhibitors (TIMPs)
      in follicular fluid of women with endometriosis, to correlate the findings with
      IVF outcome, and to examine the therapeutic potential of progesterone
      supplementation in restoring the fine balance between MMPs and TIMPs. DESIGN:
      Prospective case-control clinical study. SETTING: Infertility clinic and
      reproductive health research unit. PATIENT(S): A total of 340 infertile women
      undergoing IVF. INTERVENTION(S): Natural micronized progesterone capsules were
      administered for luteal support. MAIN OUTCOME MEASURE(S): Association of MMPs 2
      and 9 and TIMP-1 with oocyte maturity and embryo development. RESULT(S): An
      abnormal expression of MMP-2, MMP-9, and TIMP-1 with extensive MMP-9/TIMP-1
      imbalance in women with endometriosis undergoing IVF was observed. Transforming
      growth factor beta1 plays an important role in these women with possible
      involvement of Smad-2 and -3 proteins. Progesterone supplementation improves the
      imbalance in MMP-9/TIMP-1 ratio significantly in women with endometriosis who
      conceive after IVF. CONCLUSION(S): Increase in MMP-2 and -9 and decrease in TIMP
      1 expression was associated with poor oocyte and embryo development in women with
      endometriosis undergoing IVF. MMP-9/TIMP-1 balance was highly affected in these
      women, and progesterone supplementation appeared to restore this imbalance to a
      considerable degree.

PMID- 23557757
TI  - Functional neuroimaging of emotional processing in women with polycystic ovary
      syndrome: a case-control pilot study.
AB  - OBJECTIVE: To evaluate emotional processing in women with insulin-resistant
      polycystic ovary syndrome (IR-PCOS) and its relationship to glucose regulation
      and the mu-opioid system. DESIGN: Case-control pilot. SETTING: Tertiary referring
      medical center. PATIENT(S): Seven women with IR-PCOS and five non-insulin
      resistant controls, aged 21-40 years, recruited from the general population.
      INTERVENTION(S): Sixteen weeks of metformin (1,500 mg/day) in women with IR-PCOS.
      MAIN OUTCOME MEASURE(S): Assessment of mood, metabolic function, and neuronal
      activation during an emotional task using functional magnetic resonance imaging
      (fMRI), and mu-opioid receptor availability using positive emission tomography
      (PET). RESULT(S): We found that insulin-resistant PCOS patients [1] had greater
      limbic activation during an emotion task than controls (n = 5); [2] trended
      toward decreased positive affect and increased trait anxiety; [3] after metformin
      treatment, had limbic activation that no longer differed from controls; and [4]
      had positive correlations between fMRI limbic activation during emotional
      processing and mu-opioid binding potential. CONCLUSION(S): Patients with IR-PCOS
      had greater regional activation during an emotion task than the controls,
      although this resolved with metformin therapy. Alterations in mu-opioid
      neurotransmission may underlie limbic system activity and mood disorders in IR
      PCOS.

PMID- 23557758
TI  - Complex networks of multiple factors in the pathogenesis of uterine leiomyoma.
AB  - OBJECTIVE: To summarize the information regarding pathogenetic factors of
      leiomyoma formation and growth, and to make a simple integrated pathogenetic view
      of this tumor for further thinking to establish new therapeutic options. DESIGN:
      PubMed and Google Scholar searches were conducted to identify the relevant
      studies on pathogenesis of uterine leiomyoma, which are hereby reviewed and
      discussed. SETTING: Academic medical center. PATIENT(S): Not applicable.
      INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Not applicable.
      RESULT(S): To date, the pathogenesis of uterine leiomyomas is not well
      understood. However, genetic alterations (especially MED12 and HMGA2) and
      involvement of epigenetic mechanisms (DNA methylation, histone modifications, and
      microRNA) in leiomyoma provide the clue of initiator of this tumor. Estrogens and
      P are considered as promoters of leiomyoma growth, and growth factors, cytokines,
      and chemokines are thought to be as potential effectors of estrogens and P.
      Extracellular matrix components are a major structural part of leiomyoma tissue
      that are abnormally orientated and can modify mechanical stress on cells, which
      leads to activation of internal mechanical signaling and may contribute to
      leiomyoma growth. CONCLUSION(S): Besides many genetics and epigenetic factors,
      the important link among the sex steroids, growth factors, cytokines, chemokines,
      and extracellular matrix and their involvement in cell proliferation, fibrotic
      processes, apoptosis, and angiogenesis are implicating a complex network in
      leiomyoma formation and growth. Those findings could provide information to
      establish future therapeutic options for the management of this tumor.

PMID- 23557759
TI  - Estrogen receptor beta agonist diarylpropionitrile inhibits lipopolysaccharide
      induced regulated on activation normal T cell expressed and secreted (RANTES)
      production in macrophages by repressing nuclear factor kappaB activation.
AB  - OBJECTIVE: To investigate the effect of the estrogen receptor-beta (ERbeta)
      agonist diarylpropionitrile (DPN) on lipopolysaccharide (LPS)-induced regulated
      on activation normal T cell expressed and secreted (RANTES) production in
      macrophages and the possible mechanisms. DESIGN: Cellular and molecular biology
      experimental study. SETTING: University-based research laboratory. PATIENT(S):
      None. INTERVENTION(S): ERbeta mRNA and protein expression determined in murine
      macrophage cell line RAW264.7 cells using reverse-transcription polymerase chain
      reaction and Western blot analysis; RANTES production detected by ELISA in LPS
      stimulated RAW264.7 cells and ERbeta knockdown RAW264.7 cells after the addition
      of DPN, phosphorylation of p65 and IkappaB degradation detected by Western blot
      analysis; and nuclear accumulation of p65 visualized using immunofluorescence.
      MAIN OUTCOME MEASURE(S): LPS-induced RANTES production and phosphorylation of p65
      and IkappaB. RESULT(S): ERbeta was expressed in RAW264.7 cells, and DPN
      statistically significantly decreased LPS-induced RANTES production in RAW264.7
      cells. Small interfering RNA targeting the ERbeta gene inhibited the effect of
      DPN on RANTES production. In addition, DPN inhibited nuclear translocation and
      phosphorylation of p65 by inhibiting IkappaB degradation and thus prohibited the
      activation of nuclear factor kappaB (NF-kappaB). CONCLUSION(S):
      Diarylpropionitrile down-regulates LPS-induced RANTES production via ERbeta. This
      effect of DPN is likely due to repression of nuclear factor kappaB activation.

PMID- 23557760
TI  - Mitochondrial activation in the growth-restricted fetus of monochorionic twins.
AB  - OBJECTIVE: To study the regulatory mechanisms of selective intrauterine growth
      restriction (sIUGR) independent of confounding genetic factors, monochorionic
      (MC) twins are the ideal model, because they have identical genomic DNA. We
      hypothesize that the intrauterine growth restriction fetus has mitochondrial
      activation compared with its larger counterpart, and sought to demonstrate this
      using the MC twin model. DESIGN: Fetal cord blood and amniotic fluid of MC twins
      were prospectively collected during delivery. Mitochondrial DNA of cord blood was
      measured using real-time quantitative polymerase chain reaction (PCR), and
      mitochondria in amniotic fluid mesenchymal stem cells (AFMSCs) were analyzed with
      MitoTracker staining. SETTING: Tertiary referring center. PATIENT(S): Forty-three
      pairs of MC twins, including 24 pairs with sIUGR and 19 pairs without.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mitochondrial DNA contents were
      measured and presented as fold difference between the small and large fetuses.
      After staining with MitoTracker, mitochondrial intensity in AFMSCs was analyzed
      with the Image J program. RESULT(S): The fold differences of the cord blood
      mitochondrial DNA content between the small and large twins were significantly
      higher in the MC twins with sIGUR (2.5 +/- 1.2, n = 24 pairs) than in those
      without sIUGR (1.2 +/- 0.3, n = 19 pairs). In addition, mitochondrial staining
      intensities were significantly higher in the AFMSCs derived from growth
      restricted fetuses than from control fetuses. CONCLUSION(S): Mitochondrial
      activation in the sIUGR fetus of MC twins was likely regulated by locally adverse
      placental and blood flow conditions, instead of genetic factors.

PMID- 23557761
TI  - Current status of uterus transplantation in primates and issues for clinical
      application.
AB  - OBJECTIVE: To clarify the current status of uterus transplantation (UT) and the
      medical, ethical, and social problems surrounding UT. DESIGN: Systematic review.
      SETTING: Not applicable. PATIENT(S): Mainly nonhuman primates and humans.
      INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): A systematic search of
      Pubmed with the terms "uterus/uterine transplantation" was performed for English
      language articles to review the current status of UT and issues associated with
      its clinical application, with a focus on nonhuman primate and human studies on
      UT. RESULT(S): The first UT procedure in humans was conducted for a patient with
      absolute uterine infertility in Saudi Arabia in 2000. The transplanted uterus was
      removed after 99 days owing to prolapse and necrosis. That attempt led to a
      greater focus on basic UT experiments in animal models, including nonhuman
      primates. The subsequent accumulation of basic data has led to performance of UT
      in humans by groups in Turkey and Sweden. However, there has yet to be a
      pregnancy or delivery after allo-UT in primates. Moreover, there are many
      medical, ethical, and social problems that require examination before clinical
      application. CONCLUSION(S): Clinical application of UT has just begun, but more
      basic data are needed and medical, ethical, and social problems require thorough
      discussion before clinical application.

PMID- 23557762
TI  - Is the fertile window extended in women with polycystic ovary syndrome? Utilizing
      the Society for Assisted Reproductive Technology registry to assess the impact of
      reproductive aging on live-birth rate.
AB  - OBJECTIVE: To assess whether women with polycystic ovary syndrome (PCOS) follow
      the same age-related decline in IVF outcomes as women with tubal factor
      infertility over the reproductive life span. PCOS is characterized by increased
      ovarian reserve as assessed by antral follicle counts and anti-Mullerian hormone
      levels. It is unclear whether these surrogate markers of ovarian reserve reflect
      a true lengthening of the reproductive window. DESIGN: Retrospective cohort.
      SETTING: Not applicable. PATIENT(S): Women with PCOS and tubal factor infertility
      (42,286 cycles). INTERVENTION(S): IVF. MAIN OUTCOME MEASURE(S): Pregnancy and
      live-birth rates. RESULT(S): The mean number of oocytes retrieved was higher in
      women with PCOS compared with in women with tubal factor (16.4 vs. 12.8; odds
      ratio [OR], 1.27; 95% confidence interval [CI], 1.25-1.29). The clinical
      pregnancy (42.5% vs. 35.8%; OR, 1.32; 95% CI, 1.27-1.38) and live-birth rates
      were also increased in women with PCOS (34.8% vs. 29.1%; OR, 1.30; 95% CI, 1.24
      1.35). A similar rate of decline in clinical pregnancy and live-birth rates was
      noted in both groups (20-44 years). The implantation, clinical pregnancy,
      miscarriage, and live-birth rates were not significantly different for each year
      after age 40 in the two groups. CONCLUSION(S): Despite a higher oocyte yield in
      all age groups, women with PCOS over age 40 had similar clinical pregnancy and
      live-birth rates compared with women with tubal factor infertility. These
      findings suggest that the reproductive window may not be extended in PCOS and
      that patients with infertility should be treated in a timely manner despite
      indicators of high ovarian reserve.

PMID- 23557763
TI  - Phenotypic comparison of Caucasian and Asian women with polycystic ovary
      syndrome: a cross-sectional study.
AB  - OBJECTIVE: To determine whether manifestations of polycystic ovary syndrome
      (PCOS), particularly androgen excess, differ between Caucasian and Asian women in
      the San Francisco Bay Area. DESIGN: Cross-sectional study. SETTING:
      Multidisciplinary PCOS clinic at a tertiary academic center. PATIENT(S): 121
      Caucasian and 28 Asian women, aged 18-44, examined between 2006 and 2011 with
      PCOS verified by a reproductive endocrinologist and dermatologist according to
      the Rotterdam criteria. INTERVENTION(S): Transvaginal ultrasounds, comprehensive
      dermatologic exams, and serum testing. MAIN OUTCOME MEASURE(S): Hirsutism defined
      as a modified Ferriman-Gallwey (mFG) score >= 8, acne, androgenic alopecia, and
      biochemical hyperandrogenism. RESULT(S): Caucasian and Asian women had a similar
      prevalence of all measures of androgen excess. Both groups had similar total mFG
      scores and site-specific mFG scores, except Asian women had a lower site-specific
      mFG score for the chest. Although Asian women were more likely to use laser hair
      removal, the results were unchanged when the women with a history of laser hair
      removal were excluded. CONCLUSION(S): Caucasian and Asian women with PCOS living
      in the same geographic region had a similar prevalence of hirsutism as well as
      other markers for androgen excess. Further studies are necessary to evaluate the
      need for ethnic-specific mFG scores in women with PCOS.

PMID- 23557766
TI  - Genomic DNA in human blastocoele fluid.
AB  - IVF often requires embryo cryopreservation through vitrification. During the
      vitrification process, the embryos can be collapsed by withdrawing the
      blastocoele fluid. The metabolomic profile of blastocoele fluid has been recently
      investigated by high-performance liquid chromatography-electrospray ionization
      mass spectrometry to provide metabolite information that can help estimations of
      implantation efficiency. However, the presence of embryo DNA in blastocoele fluid
      has not been reported to date. This study shows using real-time PCR that genomic
      DNA was present in about 90% of blastocoele fluid samples harvested during the
      vitrification procedure. Moreover, the potential for determining embryo sex
      directly from blastocoele fluid is demonstrated by amplifying the multicopy genes
      TSPY1 (on the Y chromosome) and TBC1D3 (on chromosome 17). This opens up the
      possibility of screening embryos from couples carrying an X-linked disorder to
      identify male embryos at high risk of disease. The application of whole-genome
      amplification technologies to fluid samples is also shown to be feasible,
      potentially allowing more comprehensive genetic tests. As proof of principle,
      microarray comparative genomic hybridization was attempted to confirm the sex of
      embryos as well as detect several aneuploidies. However, further studies are
      needed to validate this approach and confirm that the accuracy is sufficient for
      diagnostic purposes.

PMID- 23557767
TI  - Embryonic DNA sampling without biopsy: the beginnings of non-invasive PGD?

PMID- 23557768
TI  - SEM-EDX, Raman and infrared spectroscopic characterization of the phosphate
      mineral frondelite (Mn2+)(Fe3+)4(PO4)3(OH)5.
AB  - We have analyzed a frondelite mineral sample from the Cigana mine, located in the
      municipality of Conselheiro Pena, a well-known pegmatite in Brazil. In the Cigana
      pegmatite, secondary phosphates, namely eosphorite, fairfieldite, fluorapatite,
      frondelite, gormanite, hureaulite, lithiophilite, reddingite and vivianite are
      common minerals in miarolitic cavities and in massive blocks after triphylite.
      The chemical formula was determined as (Mn0.68,
      Fe0.32)(Fe(3+))3,72(PO4)3.17(OH)4.99. The structure of the mineral was assessed
      using vibrational spectroscopy. Bands attributed to the stretching and bending
      modes of PO4(3-) and HOPO3(3-) units were identified. The observation of multiple
      bands supports the concept of symmetry reduction of the phosphate anion in the
      frondelite structure. Sharp Raman and infrared bands at 3581 cm(-1) is assigned
      to the OH stretching vibration. Broad Raman bands at 3063, 3529 and 3365 cm(-1)
      are attributed to water stretching vibrational modes.

PMID- 23557769
TI  - Spectral, thermal and optical-electrical properties of the layer-by-layer
      deposited thin film of nano Zn(II)-8-hydroxy-5-nitrosoquinolate complex.
AB  - Zinc(II)-8-hydroxy-5-nitrosoquinolate, [Zn(II)-(HNOQ)2], was synthesized and
      assembled as a deposited thin film of nano-metal complex by a rapid, direct,
      simple and efficient procedure based on layer-by-layer chemical deposition
      technique. Stoichiometric identification and structural characterization of
      [Zn(II)-(HNOQ)2] were confirmed by electron impact mass spectrometry (EI-MS) and
      Fourier Transform infrared spectroscopy (FT-IR). Surface morphology was studied
      by using a scanning electron microscope imaging (SEM) and the particle size was
      found to be in the range of 23-49 nm. Thermal stability of [Zn(II)-(HNOQ)2] was
      studied and the thermal parameters were evaluated using thermal gravimetric
      analysis (TGA). The current density-voltage measurements showed that the current
      flow is dominated by a space charge limited and influenced by traps under high
      bias. The optical properties of [Zn(II)-(HNOQ)2] thin films were found to exhibit
      two direct allowed transitions at 2.4 and 1.0 eV, respectively.

PMID- 23557770
TI  - Synthesis and evaluation of gold(III) complexes as efficient DNA binders and
      cytotoxic agents.
AB  - In recent years, great interest has been focused on gold(III) complexes as
      cytotoxic and antitumor drugs. Recent studies demonstrated that simple bidentate
      or polydentate ligands containing nitrogen donor atoms may offer sufficient redox
      stabilization to produce viable Au(III) anticancer drug targets under physiologic
      conditions. So, we have synthesized square planer Au(III) complexes of type
      [Au(A(n))Clx].Cly and characterized them using UV-Vis absorption, C, H, N
      elemental analysis, FT-IR, LC-MS, (1)H and (13)C NMR spectroscopy. These
      compounds manifested significant cytotoxic properties in vitro for brine shrimp
      lethality bioassay. The metal complexes were screened for series of DNA binding
      activity using UV-Vis absorption titration, hydrodynamic measurement and thermal
      DNA denaturation study. The nucleolytic activity was performed on plasmid pUC19
      DNA. The Michaelis-Menten kinetic studies were performed to evaluate rate of
      enhancement in metal complexes mediated DNA cleavage over the non-catalyzed DNA
      cleavage.

PMID- 23557771
TI  - Crystal growth, spectral, optical and thermal properties of semiorganic nonlinear
      optical material: picolinic acid hydrochloride.
AB  - The bulk single crystal of 2-picolinic acid hydrochloride (PHCL) (a semi-organic
      nonlinear optical material of dimensions 25*15*10 mm(3)) was successfully grown
      by slow solvent evaporation technique. The XRD results revealed the cell
      parameters and the centrosymmetric nature of the crystal structure. FT-IR
      spectral study identified the functional groups, nature of bonding and their bond
      strength. The UV-Vis-NIR studies recognized the optical transmittance window and
      the lower cut off wavelength of the PHCL crystal and thus it could be performed
      as a NLO material. (1)H NMR and (13)CNMR spectra were correlated with the XRD
      standard for the molecular structure reveals harmony of the materials. Thermal
      properties of the crystal were studied by thermo gravimetric analysis (TGA) and
      differential thermal analysis (DTA); the derived kinetic parameter values support
      the intuitive association of picolinicacid and HCl leads to the spontaneous
      formation of PHCL with a first order reaction. The presence of a proton and a
      proton acceptor groups provide the necessary stability to induce charge asymmetry
      in the PHCL structure. The load dependent hardness values of the crystal were
      measured by microhardness testing.

PMID- 23557772
TI  - Structural, vibrational, electronic and NMR spectral analysis of 3-chloro-6
      methoxypyridazine by DFT calculations.
AB  - In this work, the FT-Raman and FT-Infrared spectra of 3-chloro-6
      methoxypyridazine sample were measured to elucidate the spectroscopic properties
      of title molecule in the spectral range of 3500-50 cm(-1) and 4000-400 cm(-1),
      respectively. The molecular geometry and vibrational frequencies of 3-chloro-6
      methoxypyridazine in the ground state were calculated using the DFT/B3LYP/6
      31G(d),6-311G(d,p) level. The recorded FT-IR and FT-Raman spectral measurements
      favor the calculated structural parameters which are further supported by
      spectral simulation. The difference between the observed and scaled wavenumber
      values of most of the fundamentals is very small. The UV-Visible absorption
      spectrum of the compound that dissolved in methanol was recorded in the range of
      800-200 nm. The formation of hydrogen bond and the most possible interaction are
      explained using natural bond orbital (NBO) analysis. The isotropic chemical shift
      computed by (13)C and (1)H NMR analysis also shows good agreement with
      experimental observations. In addition, the molecular electrostatic potential
      (MEP) and frontier molecular orbitals (FMOs) analysis of the title compound were
      investigated using theoretical calculations.

PMID- 23557773
TI  - Quantum chemical study of the donor-bridge-acceptor triphenylamine based
      sensitizers.
AB  - Quantum chemical calculations were carried to investigate the electron coupling,
      electron injection, electronic and photophysical properties of 2-cyano-5-(4
      (phenyl(4-vinylphenyl)amino)phenyl) penta-2,4-dienoic acid (TC4) and its
      derivatives. Geometries have been optimized by using density functional theory at
      B3LYP/6-31G(**) level of theory. The highest occupied molecular orbitals (HOMOs)
      are delocalized on triphenylamine (TPA) units while lowest unoccupied molecular
      orbitals LUMOs are localized on anchoring groups. The mono-methyl is more
      significant to lowering the energy gap than di and tri-methyl substituted ones.
      The HOMOs of the dyes are below the redox couple and LUMOs are above the
      conduction band of TiO2. We have explained the recombination barrier on the basis
      of distortion and coplanarity. The excitation energies have been computed by time
      dependent density functional theory at PCM-CAM-B3LYP/6-31G(**) level of theory.
      Enhanced bridge is encouraging to promote the electron injection, electronic
      coupling constant and light harvesting efficiency. Generally, electron injection,
      electronic coupling constant and light harvesting efficiency of new designed
      sensitizers are higher than TC4. This revealed that new materials would be
      efficient photosensitizers.

PMID- 23557774
TI  - Wet chemical synthesis, structural and spectroscopic studies of CuSe-Ag
      hierarchical sphere and drum-like microporous structure.
AB  - Nanostructural self-assembly has become field of intense research activities from
      both fundamental and technological standpoints to understanding the mechanism of
      driving forces and finding artificial methods of assembling them into continuous
      structures without any obstructions. Various exciting and refined examples of
      nanostructured self-assembly are well documented. In the present manuscript the
      crystallization process and optical properties of self assembled CuSe-Ag
      hierarchical microporous sphere and drum-like structures, synthesized by wet
      chemical method has been investigated. Thus formed structures are accumulated by
      numerous polyhedral rod-like subunits, and each unit seems to be an incomplete
      structure of a randomly grown rod. Phase analysis, purity and morphology of the
      product have been well studied by X-ray diffraction (XRD), photo-luminescent
      spectroscopy (PL), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and high resolution transmission electron microscopy (HRTEM).
      Due to their microporous structures CuSe-Ag could be potential building blocks to
      construct functional devices like sensing and several other applications. A
      possible reaction mechanism for the formation of CuSe-Ag has also been proposed.

PMID- 23557775
TI  - Synthesis of hollow gold nanoparticles on the surface of indium tin oxide glass
      and their application for plasmonic biosensor.
AB  - Hollow gold nanoparticles (HGNs) deposited on the surface of transparent indium
      tin oxide (ITO) glass have been synthesized. The silver nanoparticles were
      firstly electrodeposited directly on the ITO surface as a template without any
      organic ligands or surfactants. Then these silver nanoparticles were taken as
      sacrificial templates and the HGNs were obtained by Galvanic replacement reaction
      between HAuCl4 solution and silver nanoparticles. The localized surface plasmon
      resonance (LSPR) peak of HGNs was located at near infrared region of ~800 nm,
      which was largely red-shifted as compared to silver nanoparticles as a template.
      Moreover, the refractive index sensitivity of HGNs was enhanced to 277 nm per
      refractive index unit, which was also much higher than that of silver
      nanoparticles deposited on ITO substrate. The "clean" surface of HGNs could be
      further functionalized by special biomolecules and applied to fabrication of LSPR
      biosensors. This approach provides a potential opportunity as LSPR biosensors for
      chemical or biological analysis especially on tissue and blood samples.

PMID- 23557776
TI  - Anatase: important industrial white pigment and date-marker for artwork.
AB  - Barium sulfate, BaSO4, is shown by Raman microscopy to be readily identifiable in
      early (1920s) industrially produced anatase (TiO2) and thus, if present, may act
      as a date marker for early industrial anatase. Later processes (except that for
      producing Titanox B) did not involve usage of barium sulfate. The matter is
      relevant to the possible dating of certain artwork.

PMID- 23557777
TI  - Synthesis and spectral characterization of methyl 9(10)
      dialkylphosphonostearates.
AB  - Dimethyl, diethyl, and di-n-butyl phosphites were reacted with methyl or ethyl
      oleates using thermally initiated radical reactions. Reactions were conducted
      with or without the presence of a dilauroyl peroxide initiator. The reactions
      gave mixture of isomers with the phosphorus attached at the 9 or 10 carbon of the
      stearates. High yields (94-97%) and high purity products (98-99% by GC) were
      obtained in the presence of the initiator, while without initiator, the reaction
      was very slow resulting in very low conversions (<50% after 6 days). The
      phosphonostearate products were positively identified and thoroughly
      characterized using GC with EI-MS, FTIR, and (1)H-, (13)C-, and (31)P NMR
      spectra. GC achieved only partial resolution of the positional isomers. Principal
      component analysis was applied to successfully separate the MS-EI spectra of
      fractions from the 9- and 10-isomers. A mechanism to explain the observed MS
      fragmentation pattern and the relative abundances is proposed. 2D-NMR data
      analysis was applied to assign values of (13)C- and (1)H NMR shifts as well as P
      C and P-H splitting constants. The molecular volume and the refractive indices of
      the phosphonostearates were determined experimentally and were found to be in
      agreement with the computationally predicted values using the PM3 semi-empirical
      method and the group-contribution method of Bondi.

PMID- 23557778
TI  - Investigations on the interactions of diclofenac sodium with HSA and ctDNA using
      molecular modeling and multispectroscopic methods.
AB  - A tentative study on interaction of diclofenac sodium (DF-Na) with human serum
      albumin (HSA) and calf thymus DNA (ctDNA) was conducted by using multi
      spectroscopic and molecular modeling techniques under simulative physiological
      conditions. The results of spectroscopic measurements suggested that the
      quenching mechanisms were static quenching. Three-dimensional fluorescence
      spectroscopy clearly demonstrated the occurrence of conformational changes of HSA
      with addition of DF-Na. In addition, competitive studies with ethidium bromide
      (EB) have shown that DF-Na can bind to ctDNA relatively strong via groove
      binding. Based on the values of thermodynamic parameters and the results of
      molecular modeling, it was confirmed that hydrophobic forces and hydrogen bond
      were the mainly binding forces in DF-Na-HSA and DF-Na-DNA systems. The binding
      distance between DF-Na and HSA was also determined using the theory of the
      Forster energy transference.

PMID- 23557779
TI  - Interaction with biomacromolecules and antiproliferative activities of Mn(II),
      Ni(II), Zn(II) complexes of demethylcantharate and 2,2'-bipyridine.
AB  - Three new transition metal complexes [Mn2(DCA)2(bipy)2].5H2O (1),
      [M2(DCA)2(bipy)2(H2O)].10H2O(M=Ni(II)(2);Zn(II)(3)), (DCA=demethylcantharate, 7
      oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C8H8O5) were synthesized and
      characterized by elemental analysis, molar conductance, infrared spectra and X
      ray diffraction techniques. Each metal ion was six-coordinated in complexes.
      Complex 1 has a Mn2O2 center. Complexes 2 and 3 have asymmetric binuclear
      structure. Great amount of intermolecular hydrogen-bonding and pi-pi(*) stacking
      interactions were formed in these complex structures. The DNA-binding properties
      of complexes were investigated by electronic absorption spectra and viscosity
      measurements. The DNA binding constants Kb/(Lmol(-1)) were 1.71*10(4) (1),
      2.62*10(4) (2) and 1.59*10(4) (3) at 298 K. The complexes could quench the
      intrinsic fluorescence of bovine serum albumin (BSA) strongly through static
      quenching. The protein binding constants Ka/(L mol(-1)) were 7.27*10(4) (1),
      4.55*10(4) (2) and 7.87*10(4) L mol(-1) (3) and binding site was one. The
      complexes bind more tightly with DNA and BSA than with ligands. Complexes 1 and 3
      had stronger inhibition ratios than Na2(DCA) against human hepatoma cells (SMMC
      7721) lines and human gastric cancer cells (MGC80-3) lines in vitro. Complex 3
      showed the strongest antiproliferative activity against SMMC-7721 (IC50=29.46+/
      2.12 MUmol L(-1)) and MGC80-3 (IC50=27.02+/-2.38 MUmol L(-1)), which shows
      potential in anti-cancer drug development.

PMID- 23557780
TI  - A Delphi exercise and cluster analysis to aid in the development of potential
      classification criteria for systemic sclerosis using SSc experts and databases.
AB  - OBJECTIVES: Since the 1980 ACR classification criteria for systemic sclerosis
      (SSc) do not identify 20% with SSc, revised criteria are necessary. METHODS:
      Suggested new criteria from the literature were sent in random order to 96 SSc
      experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis
      reduced items. The Canadian Scleroderma Research Group (CSRG) database was used
      to determine the prevalence of each item. RESULTS: Seventy-one of 96 (71%)
      completed all 3 rounds; 47 items were expanded to 76 in round 2. Thirty items had
      at least 50% consensus and 18 had >75% agreement to include (a priori cut point).
      Clustering occurred for 4 categories: proximal to MCP skin involvement, vascular
      abnormalities, autoantibodies and tissue damage. Proximal to MCPs skin
      involvement identified 80% of patients. Adding one item from each of the other 3
      categories or 1 or more items from 2 of 3 remaining categories increased the
      proportion of patients classified to 94% in CSRG patients. Categories included
      (1) Vascular (dilated capillaries, telangiectasia, Raynaud's phenomenon [RP]),
      (2) Autoantibodies (anticentromere [ACA] or antitopoisomeraseI [Topo1]) and (3)
      Fibrosis/damage (esophogeal dysmotility dysphagia, sclerodactyly, digital
      ulcers). In the CSRG, 98% were identified if using proximal skin involvement; or
      sclerodactyly plus one of: RP, ACA or Topo1. CONCLUSIONS: This is a first step
      toward developing new SSc classification criteria. A Delphi exercise alone cannot
      suffice for item reduction. Also, validation prospectively in SSc patients and
      diseases that mimic SSc is needed in order to calculate sensitivity and
      specificity of future criteria.

PMID- 23557781
TI  - Astrogliosis and HSP 70 activation in neonate rats' brain exposed to sodium
      metavanadate through lactation.
AB  - The effect of sodium metavanadate (NaVO3) exposure on lipid oxidative damage in
      the CNS of suckling rats was studied. Using histological markers of cellular
      injury, we also studied the morphological alterations of neurons and astroglial
      cells in different regions of neonate rats CNS after NaVO3 exposure. Dams of
      treated litters were intraperitoneally injected with 3mgNaVO3/kgbody weight/day
      during 12days starting on post-natal day (PND) 10. On the 21st PND, four pups of
      each litter were sacrificed by decapitation and six brain areas were removed for
      lipid peroxidation assay by the thiobarbituric acid (TBA) reaction, the other
      four were transcardially perfused-fixed and their brains were removed and cut
      with a cryostat. Brain sections were processed for: NADPHd histochemistry and
      anti-HSP70, anti-GFAP and anti-S100 immunohistochemistry. The relative optical
      density of the NADPHd stained layers and of S100 (+) astrocytes and the GFAP (+)
      astrocyte surface area in Cer and Hc were measured. Although MDA levels, S100
      immunostaining and NADPHd activity didn't show differences between experimental
      and control groups, both astrogliosis and HSP70 activation were detected in Cer,
      while only the former was detected in Hc of V-exposed pups.

PMID- 23557782
TI  - Land atmosphere feedbacks and their role in the water resources of the Ganges
      basin.
AB  - The northern Indian subcontinent has frequently been identified as a hotspot for
      land atmosphere interactions. It is also a region with the highest concentration
      of irrigated land and highest (and increasing) population density in the world.
      The available water in the region with which to grow food depends on the Asian
      monsoon, groundwater and melt from Himalayan snows. Any changes or disruptions to
      these sources of water could threaten the food supply. It is therefore essential
      to understand how the land surface, and in particular irrigated land, interacts
      with the atmosphere. It is anticipated that the interactions will occur on many
      scales. To an extent the magnitude and form of these will depend on the depth of
      the atmosphere which is affected. Thus at the local, or micro, scale it is the
      surface layer (some 10 s m deep) which is cooled and moistened by the evaporation
      of irrigated water, at the meso-scale the Planetary boundary layer (up to 1 or 2
      km) will be modified - with possible atmospheric moistening, increased cloud and
      rain formation and at very large scales the whole dynamics of the south Asian
      Monsoon will be affected. This illustrates a strong interaction between the Asian
      monsoon and the regional topography. Of considerable significance is the finding
      in this paper that up to 60% of the evaporation from irrigated areas in the
      summer months is ultimately recycled to Himalayan rainfall and so feedbacks to
      river flows in the Ganges.

PMID- 23557784
TI  - Pupylation as a signal for proteasomal degradation in bacteria.
AB  - Posttranslational modifications in the form of covalently attached proteins like
      ubiquitin (Ub), were long considered an exclusive feature of eukaryotic
      organisms. The discovery of pupylation, the modification of lysine residues with
      a prokaryotic, ubiquitin-like protein (Pup), demonstrated that certain bacteria
      use a tagging pathway functionally related to ubiquitination in order to target
      proteins for proteasomal degradation. However, functional analogies do not
      translate into structural or mechanistic relatedness. Bacterial Pup, unlike
      eukaryotic Ub, does not adopt a beta-grasp fold, but is intrinsically disordered.
      Furthermore, isopeptide bond formation in the pupylation process is carried out
      by enzymes evolutionary descendent from glutamine synthetases. While in
      eukaryotes, the proteasome is the main energy-dependent protein degradation
      machine, bacterial proteasomes exist in addition to other architecturally related
      degradation complexes, and their specific role along with the role of pupylation
      is still poorly understood. In Mycobacterium tuberculosis (Mtb), the Pup
      proteasome system contributes to pathogenicity by supporting the bacterium's
      persistence within host macrophages. Here, we describe the mechanism and
      structural framework of pupylation and the targeting of pupylated proteins to the
      proteasome complex. Particular attention is given to the comparison of the
      bacterial Pup-proteasome system and the eukaryotic ubiquitin-proteasome system.
      Furthermore, the involvement of pupylation and proteasomal degradation in Mtb
      pathogenesis is discussed together with efforts to establish the Pup-proteasome
      system as a drug target. This article is part of a Special Issue entitled:
      Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. 

PMID- 23557785
TI  - MicroRNAs in pluripotency, reprogramming and cell fate induction.
AB  - Pluripotent stem cells display a unique expression pattern of microRNAs (miRNAs).
      These ~22 nucleotide non-coding RNAs have established a crucial role in
      controlling gene expression of pluripotent stem cells at the post-transcriptional
      level. Recent studies made important advances in identifying miRNA regulated
      processes like de novo DNA methylation, progression of the cell cycle and
      regulation of cell fate decision. miRNAs have also the ability to reprogram
      somatic cells to pluripotent stem cells and on the other hand, to induce
      differentiation of pluripotent stem cells into distinct somatic lineages.
      Previously it was published that miRNAs can direct reprogramming on its own. Here
      we provide evidence and critically discuss that the effect of miRNA depends on co
      expression of the classical reprogramming factors. During transition between
      these different cell fates distinct miRNAs adjust the levels of specific
      transcriptional programs and confer robustness to differentiation processes. This
      results in a complex network between miRNAs and their targets. The fact that
      miRNAs itself can also be regulated by its targets establishes complex regulatory
      loops. Based on bioinformatical predictions, each miRNA theoretically has
      hundreds of target genes making it even more challenging to understand the
      complete network between miRNAs and their targets.

PMID- 23557783
TI  - How early studies on secreted and membrane protein quality control gave rise to
      the ER associated degradation (ERAD) pathway: the early history of ERAD.
AB  - All newly synthesized proteins are subject to quality control check-points, which
      prevent aberrant polypeptides from harming the cell. For proteins that ultimately
      reside in the cytoplasm, components that also reside in the cytoplasm were known
      for many years to mediate quality control. Early biochemical and genetic data
      indicated that misfolded proteins were selected by molecular chaperones and then
      targeted to the proteasome (in eukaryotes) or to proteasome-like particles (in
      bacteria) for degradation. What was less clear was how secreted and integral
      membrane proteins, which in eukaryotes enter the endoplasmic reticulum (ER), were
      subject to quality control decisions. In this review, we highlight early studies
      that ultimately led to the discovery that secreted and integral membrane proteins
      also utilize several components that constitute the cytoplasmic quality control
      machinery. This component of the cellular quality control pathway is known as ER
      associated degradation, or ERAD. This article is part of a Special Issue
      entitled: Functional and structural diversity of endoplasmic reticulum. 

PMID- 23557786
TI  - Irx7, a Smarca4-regulated gene for retinal differentiation, regulates other genes
      controlled by Smarca4 in zebrafish retinas.
AB  - The iroquois 7 (irx7) in zebrafish encodes a homeodomain transcription factor
      (TF) in the retinal differentiation network regulated by smarca4, a component of
      chromatin remodeling complex. The function of Irx7 on retinal development has
      recently been revealed by antisense morpholino knockdown experiments. In
      particular, the normal expression of irx7 in the inner nuclear layer (INL) is
      essential for the differentiation of cells in the INL and the outer nuclear layer
      (ONL), as well as the dendritic projection of GCs into the inner plexiform layer
      (IPL). Irx7 also exerts its effect on retinal differentiation through activating
      the expression of TFs that specify various retinal cell types. However, the
      relationship between irx7 and the other Smarca4-regulated genes for retinal
      differentiation was not clear. This study reports an investigation of the
      regulatory role of irx7 on 13 genes including aanat2, barhl2, bhlhe22, cdh11,
      ckmt1, gnat1, irx4a, ndrg1a, nme2l, pbx1a, rcv1, robo2 and tfap2a. These genes
      were originally used in a study that characterized the cellular expression
      pattern of Smarca4-regulated genes and had a diverse expression pattern in the
      retina. Their expression in the normal wild-type (WT), Irx7-knockdown and the
      injection control embryos was characterized by in situ hybridization at 52h post
      fertilization (hpf). This is the stage when irx7's expression level is the
      highest in the developing retinas. The results indicate that the expression of 11
      of the 13 genes was reduced and one was overexpressed in the Irx7-knockdown
      retinas. Consistent with a previous report, one of these 13 genes was not
      expressed in the retina. Among the 12 Irx7-regulated genes, 11 had an expression
      change in the Irx7-knockdown retinas similar to that in the smarca4 retinas,
      indicating that Smarca4 regulates the expression of these 11 genes at least in
      part through irx7. Interestingly, bhlhe22 was only over-expressed in the Irx7
      knockdown but not the smarca4 retinas. These observations suggest a different
      regulatory mechanism on bhlhe22 expression by smarca4 and irx7.

PMID- 23557787
TI  - Designing dipolar recoupling and decoupling experiments for biological solid
      state NMR using interleaved continuous wave and RF pulse irradiation.
AB  - Rapid developments in solid-state NMR methodology have boosted this technique
      into a highly versatile tool for structural biology. The invention of
      increasingly advanced rf pulse sequences that take advantage of better hardware
      and sample preparation have played an important part in these advances. In the
      development of these new pulse sequences, researchers have taken advantage of
      analytical tools, such as average Hamiltonian theory or lately numerical methods
      based on optimal control theory. In this Account, we focus on the interplay
      between these strategies in the systematic development of simple pulse sequences
      that combines continuous wave (CW) irradiation with short pulses to obtain
      improved rf pulse, recoupling, sampling, and decoupling performance. Our initial
      work on this problem focused on the challenges associated with the increasing use
      of fully or partly deuterated proteins to obtain high-resolution, liquid-state
      like solid-state NMR spectra. Here we exploit the overwhelming presence of (2)H
      in such samples as a source of polarization and to gain structural information.
      The (2)H nuclei possess dominant quadrupolar couplings which complicate even the
      simplest operations, such as rf pulses and polarization transfer to surrounding
      nuclei. Using optimal control and easy analytical adaptations, we demonstrate
      that a series of rotor synchronized short pulses may form the basis for
      essentially ideal rf pulse performance. Using similar approaches, we design (2)H
      to (13)C polarization transfer experiments that increase the efficiency by one
      order of magnitude over standard cross polarization experiments. We demonstrate
      how we can translate advanced optimal control waveforms into simple interleaved
      CW and rf pulse methods that form a new cross polarization experiment. This
      experiment significantly improves (1)H-(15)N and (15)N-(13)C transfers, which are
      key elements in the vast majority of biological solid-state NMR experiments. In
      addition, we demonstrate how interleaved sampling of spectra exploiting
      polarization from (1)H and (2)H nuclei can substantially enhance the sensitivity
      of such experiments. Finally, we present systematic development of (1)H
      decoupling methods where CW irradiation of moderate amplitude is interleaved with
      strong rotor-synchronized refocusing pulses. We show that these sequences remove
      residual cross terms between dipolar coupling and chemical shielding anisotropy
      more effectively and improve the spectral resolution over that observed in
      current state-of-the-art methods.

PMID- 23557788
TI  - Reduction of morbidity related to emergency access to dialysis with very low
      protein diet supplemented with ketoacids (VLPD+KA).
AB  - OBJECTIVE: To delay the beginning of the renal replacement therapy (RRT) until
      the AV fistula is either made and mature or the training for peritoneal dialysis
      (PD) is given. DESIGN: Prospective study. SETTING: Nephrology's Ambulatory,
      Hospital Servidor Publico Estadual. PATIENTS: 21 patients with chronic kidney
      disease (CKD) have been followed. METHODS: For a period of 30 days, a VLPD+KA
      would be prescribed until the AV fistula was made or the PD training was given
      The patients were evaluated prior to the beginning of the VLPD+KA, on the 15th
      and the 30th day, and at the end of the study, with physical and nutritional
      evaluation, laboratory tests and 24-hour excretion of urinary urea and urinary
      protein, creatinine and urea residual clearance. RESULTS: 47.6% (10/21) of the
      patients have initiated HD with matured and suitable AV fistula made in 30 days;
      33.3% (7/21) of the patients have been unfit to initiate RRT, even though with
      sufficient time for the creation of the AV fistula or the training for PD due to
      AV fistula thrombosis; 14.3% (3/21) of the patients have remained in the study
      with no need for dialysis, and 4.8% (1/21) have been excluded on the grounds of
      not having adhered to the VLPD+KA. The anthropometric parameters and the energy
      intake have not differed from one period to the other. CONCLUSION: The VLPD+KA is
      safe to maintain the nutritional status of patients of CKD until the AV fistula
      is made or the PD training is given.

PMID- 23557789
TI  - Bone mineral density 5 years after parathyroidectomy in hemodialysis patients
      with secondary hyperparathyroidism.
AB  - BACKGROUND: Whether bone mineral density (BMD) is improved at 5 years after
      parathyroidectomy (PTx) for secondary hyperparathyroidism (SHPT) remains unknown.
      OBJECTIVE: To investigate BMD after PTx by dual energy X-ray absorptiometry
      (DXA). METHODS: BMD was measured at the distal 1/3 of the radius (non-shunt side)
      and at the lumbar supine (L2-L4, lateral view) before and 5 years after PTx in 35
      hemodialysis patients who had undergone surgery from April 1994 to May 2004. The
      data were analyzed retrospectively. RESULTS: Intact PTH decreased significantly
      from 1,100 +/- 530 (range: 446 - 2,300) pg/ ml before PTx to 75 +/- 68 (2 - 251)
      pg/ml at 5 years after PTx (p < 0.01). Before PTx, the radial BMD and lumbar BMD
      were both decreased -3.3 +/- 1.9 SD and -1.3 +/- 2.4 SD compared with the
      corresponding normal mean T-score, respectively. Radial BMD increased
      significantly from 0.522 +/- 0.113 g/cm2 before PTx to 0.545 +/- 0.114 g/cm2 (p =
      0.01) at 5 years after PTx, while the T-score improved to -2.8 +/- 2.0 SD. In
      contrast, lumbar BMD showed no significant change between before (0.734 +/- 0.202
      g/cm2) and 5 years after PTx (0.746 +/- 0.199 g/cm2), and neither did the T-score
      (-1.1 +/- 2.3 SD). None of the patients suffered any fractures during follow up.
      CONCLUSION: These findings indicate that maintaining iPTH at < 300 pg/ml for 5
      years after PTx results in an increase of radial BMD in SHPT patients with
      preoperative BMD levels in the osteoporosis range (below -2.5 SD) according to
      the WHO, as well as stabilizing lumbar BMD.

PMID- 23557790
TI  - Brucella and peritoneal dialysis related peritonitis: case report and review of
      literature.
AB  - Isolated case reports of peritonitis due to Brucella spp. during peritoneal
      dialysis (PD) continue to surface in the medical literature. However, the optimal
      treatment regimen for these patients, in particular with regards to the fate of
      PD catheter, is still largely unknown. We report a case of brucella peritonitis
      successfully treated with intraperitoneal administration of amikacin, along with
      oral rifampicin and doxycycline but without catheter removal. Furthermore, we
      have reviewed the literature up until present day. 

PMID- 23557791
TI  - Tonsillectomy with steroid pulse therapy has more effect on the relapse rate than
      steroid pulse monotherapy in IgA nephropathy patients.
AB  - AIMS: Both steroid pulse (SP) monotherapy and the combination of tonsillectomy
      and SP therapy (TSP) are effective for achieving clinical remission (CR), defined
      as negative hematuria and proteinuria, in patients with IgA nephropathy (IgAN).
      The role of tonsillectomy in the treatment of IgAN has been analyzed only from
      the aspect of CR or renal survival after TSP treatment, so there is no evidence
      of its effect on the relapse after CR. METHODS: We retrospectively investigated
      relapse (re-appearance of urinary abnormalities) from CR after TSP or SP
      monotherapy in 62 IgAN patients (mean follow-up, 70.1 +/- 35.3 months). The SP
      therapy comprised 0.5 g methylprednisolone administered intravenously on 3
      consecutive days followed by oral prednisolone (30 mg/day) on 4 consecutive days,
      with the course repeated 3 times. Oral prednisolone (30 mg/day) was then given on
      alternative days and gradually tapered and finished over 1 year. Tonsillectomy
      was performed either before or within 6 months of starting SP therapy. RESULTS:
      At baseline, the mean age was 34.6 years, the mean serum creatinine (Cr) level
      was 0.9 mg/dl, and the mean level of proteinuria was 876 mg/day. There were no
      differences between the TSP group (41 patients) and SP monotherapy group (21
      patients). In total, 24 of the TSP and 10 of the SP patients achieved CR. Of the
      34 patients who achieved CR, 13 relapsed after TSP or SP monotherapy. Using
      Kaplan-Meier analysis, tonsillectomy was associated with a lower incidence of
      relapse from CR after treatment (p = 0.045). Multivariate Cox regression analysis
      revealed that tonsillectomy reduced the rate of from CR after SP therapy.
      CONCLUSION: Tonsillectomy was associated with a reduction in the relapse rate
      from CR after SP therapy in IgAN patients.

PMID- 23557792
TI  - Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in
      healthy volunteers.
AB  - BACKGROUND: Cocoa is rich in flavonoids, has anti-oxidative properties and
      increases the bioavailability of nitric oxide (NO). Adequate renal tissue
      oxygenation is crucial for the maintenance of renal function. The goal of this
      study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal
      tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC).
      METHODS: Ten healthy volunteers with preserved kidney function (mean age +/- SD
      35 +/- 12 years, 70% women, BMI 21 +/- 3 kg/m2) underwent blood oxygenation level
      dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the
      ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by
      the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean
      R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2*
      indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at
      least 1 week later, before and 2 hours after the intake of 1 g/kg WC. RESULTS:
      The mean medullary R2* was lower after DC intake compared to baseline (28.2 +/-
      1.3 s-1 vs. 29.6 +/- 1.3 s-1, p = 0.04), whereas cortical and medullary R2*
      values did not change after WC intake. The change in medullary R2* correlated
      with the level of circulating (epi)catechines, metabolites of flavonoids (r =
      0.74, p = 0.037), and was independent of plasma renin activity. CONCLUSION: This
      study suggests for the first time an increase of renal medullary oxygenation
      after intake of dark chocolate. Whether this is linked to flavonoid-induced
      changes in renal perfusion or oxygen consumption, and whether cocoa has
      potentially renoprotective properties, merits further study.

PMID- 23557793
TI  - Renal recovery with eculizumab in atypical hemolytic uremic syndrome following
      prolonged dialysis.
AB  - Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) which
      encompasses hemolytic anemia, thrombocytopenia, and organ impairment. Around 10%
      of cases are atypical HUS (aHUS), a rare disease with poor outcomes caused by
      uncontrolled activation of the alternative complement pathway. This case
      describes a young woman with clinical manifestations compatible with TMA during
      childhood and adolescence who was formally diagnosed with aHUS at the age of 21.
      She was managed with intensive plasma exchange and hemodialysis, which failed to
      improve her severe acute kidney injury and other hematological manifestations of
      aHUS. This was further compounded by several episodes of flash pulmonary edema
      and the posterior reversible encephalopathy syndrome (PRES). Treatment with the
      monoclonal anti-C5 inhibitor, eculizumab, improved all hematological parameters
      with almost full renal recovery following 3.5 months of dialysis. So far, long
      term use of eculizumab (> 11 months) continues to be effective and without
      complication. Our case illustrates the difficulty but importance of early
      consideration of aHUS in patients presenting with TMA. More importantly, we
      highlight that near-normal renal recovery may be attained with eculizumab in
      adults even after a long dependence on dialysis - an observation that has not
      been reported in the literature so far. 

PMID- 23557794
TI  - mTOR inhibitors in advanced breast cancer: ready for prime time?
AB  - Current therapeutic approaches for advanced breast cancer frequently target
      receptors mediating cell survival and proliferation, such as the estrogen
      receptor and/or progesterone receptor and human epidermal growth factor receptor
      2. Although these approaches are effective for many patients, treatment
      resistance is common. Therefore, new treatment approaches are needed for patients
      with advanced breast cancer. Mammalian target of rapamycin is a highly conserved
      serine-threonine kinase that acts as a major signaling hub that integrates and
      synergizes with cellular proliferation, survival, and/or motility signals
      mediated by estrogen receptor, human epidermal growth factor receptor-2, and
      other receptor tyrosine kinases. Dysregulation of mammalian target of rapamycin
      signaling occurs in various tumor types, including breast cancer, and has been
      associated with cancer pathogenesis, disease progression, and treatment
      resistance. Recent clinical trials show that combined inhibition of mammalian
      target of rapamycin and estrogen receptor represents an effective strategy for
      treating hormone receptor-positive advanced breast cancer progressing on
      nonsteroidal aromatase inhibitor therapy, and data from ongoing trials combining
      mammalian target of rapamycin inhibition with human epidermal growth factor
      receptor-2-targeted therapy are awaited. This review focuses on the molecular
      rationale underlying strategies to enhance sensitivity to treatment in hormone
      receptor-positive and human epidermal growth factor receptor-2-positive advanced
      breast cancer, the clinical efficacy of such approaches, and future perspectives.

PMID- 23557795
TI  - Interleukin-27 inhibits phagosomal acidification by blocking vacuolar ATPases.
AB  - Interleukin (IL)-27 is a unique cytokine that has a dual role in immune
      responses. It was originally described to promote Th1 differentiation but also
      suppresses inflammation by inhibiting these and other inflammatory T cell
      subsets. Inhibition of inflammatory activity in macrophages has also been
      reported. These reports have largely focused on cytokine profiles or signaling
      mechanisms. To date, there have been no reports of how IL-27 may directly
      influence cellular mechanisms that operate to control microbial growth. Formation
      of a phagolysosome that acquires antimicrobial properties is an essential step
      for destruction of pathogens or pathogen-derived materials that are internalized
      by macrophages. Here we report that IL-27 has a profound influence on this
      critical innate immunity pathway. Treatment of human macrophages with IL-27
      interferes with the acidification of phagosomes by reducing protein levels of V
      ATPase and impairs control of bacterial pathogens.

PMID- 23557796
TI  - hsBAFF promotes proliferation and survival in cultured B lymphocytes via calcium
      signaling activation of mTOR pathway.
AB  - B-cell activating factor of the TNF family (BAFF, also called BLyS, TALL-1,
      THANK, or zTNF4) has revealed its critical function in B lymphocyte proliferation
      and survival, as well as the pathogenesis of autoimmune disease. However, the
      molecular mechanisms of excess BAFF-extended aggressive B lymphocytes have not
      been completely defined. Here we show that excessive hsBAFF-elevated [Ca(2+)]i
      activated mammalian target of rapamycin (mTOR) signaling pathway, leading to
      proliferation and survival in B lymphocytes. This is supported by the findings
      that intracellular Ca(2+) chelator (BAPTA/AM) or mTOR inhibitor (rapamycin)
      abolished the events. Sequentially, we observed that preventing [Ca(2+)]i
      elevation using EGTA or 2-APB dramatically inhibited hsBAFF activation of mTOR
      signaling, as well as cell growth and survival, suggesting that hsBAFF-induced
      extracellular Ca(2+) influx and ER Ca(2+) release elevates [Ca(2+)]i contributing
      to B lymphocyte proliferation and survival via activation of mTOR signaling.
      Further, we noticed that pretreatment with BAPTA/AM, EGTA or 2-APB blocked hsBAFF
      increased phosphorylation of calcium/calmodulin-dependent protein kinase II
      (CaMKII), and inhibiting CaMKII with KN93 attenuated hsBAFF-activated mTOR
      signaling, as well as cell growth and survival, revealing that the effects of
      hsBAFF-elevated [Ca(2+)]i on mTOR signaling as well as proliferation and survival
      in B lymphocytes is through stimulating phosphorylation of CaMKII. The results
      indicate that hsBAFF activates mTOR pathway triggering B lymphocyte proliferation
      and survival by calcium signaling. Our findings suggest that manipulation of
      intracellular Ca(2+) level or CaMKII and mTOR activity may be exploited for the
      prevention of excessive BAFF-induced aggressive B lymphocyte disorders and
      autoimmune diseases.

PMID- 23557797
TI  - Cytokines signatures in short and long-term stable renal transplanted patients.
AB  - Despite the evidences showing the relevance of regulatory immune-mediated
      mechanisms to guarantee the stable graft function in renal transplanted patients,
      studies focusing on the immune response observed over a long-term period after
      renal transplantation are still limited. Several efforts have been done to
      establish novel biomarkers with relevant predictive values that could be used as
      prognostic laboratorial tools to monitor the complex network triggered through
      time after kidney transplantation. In this study, we have evaluated the pro
      inflammatory and regulatory patterns of plasma cytokines in a group of 120 renal
      transplanted patients with stable graft function ranging from 1 to 160 months.
      Our data demonstrated an overall predominance of regulatory cytokines short-term
      after renal transplantation (1-24 months) with peaks of IL-4, IL-5 and IL-10.
      Moreover, a slight peak of TNF-alpha was observed 25-60 months after renal
      transplantation. Following a gap of stable cytokine profile (61-120 months),
      peaks of pro-inflammatory cytokines IL-8, IL-6, IL1beta, TNF-alpha and IL-12 were
      observed later on (>120 months) after renal transplantation. Additionally, the
      categorical analysis of "low" or "high" cytokine producers re-enforce the
      occurrence of an overall regulatory status early-after stable renal graft
      function with a predominant pro-inflammatory pattern later on long-term renal
      transplantation. Taken together, our data suggest that IL-5 is a good biomarker
      associated with short-term stable renal function, whereas IL-12 seems to be a
      relevant pro-inflammatory element in long-term renal transplanted patients.

PMID- 23557798
TI  - The activation and regulation of IL-17 receptor mediated signaling.
AB  - Interleukin-17 (IL-17), the signature cytokine produced by T helper 17 (Th17)
      cells, plays pivotal roles in host defense responses against microbial invasion,
      as well as in the pathogenesis of autoimmune diseases and allergic syndromes. IL
      17 activates several downstream signaling pathways including NF-kappaB, MAPKs and
      C/EBPs to induce gene expression of antibacterial peptides, proinflammatory
      chemokines and cytokines and matrix metalloproteinases (MMPs). IL-17 can also
      stabilize mRNAs of genes induced by TNFalpha. Although the physiological and
      pathological functions of IL-17 have been studied for many years, the landscape
      of its signaling transduction has not been described until recently. The
      cytosolic adaptor molecule Act1 (also known as CIKS) is considered as the master
      mediator of IL-17 signaling. In this review, we will summarize recent progress on
      activation and regulation of IL-17 mediated signal transduction, especially on
      Act1 mediated regulation of the signaling.

PMID- 23557799
TI  - Haplotypes of IL-12Rbeta1 impact on the clinical phenotype of hidradenitis
      suppurativa.
AB  - Antigen presentation in chronic skin disorders is mediated through the
      interleukin (IL)-12/IL-23 pathway and, hence, through the IL-12 receptor. Recent
      evidence suggesting dysregulated antigen presentation in skin lesions of
      hidradenitis suppurativa (HS) led to investigate the role of single nucleotide
      polymorphisms (SNPs) of the gene IL-12RB1 coding for the IL12-Rbeta1 receptor
      subunit. Genomic DNA was isolated from 139 patients and 113 healthy controls;
      nine SNPs in the transcribed region of IL12RB1 were genotyped. No significant
      differences of genotype and allele frequencies were found between the two groups.
      Two common haplotypes were recognized, namely h1 and h2. Carriage of h2 related
      with minor frequency alleles was associated with a greater risk for the
      acquisition of Hurley III disease stage and with the involvement of a greater
      number of skin areas. Patients with the h1 haplotype presented disease at an
      older age. This is the genetic study enrolling the largest number of patients
      with HS to date. Although SNPs of IL12RB1 do not seem to convey genetic
      predisposition, they are associated directly with the phenotype of the disease.

PMID- 23557800
TI  - Role of interleukin-21 isoform in dextran sulfate sodium (DSS)-induced colitis.
AB  - Interleukin-21 (IL-21) is overproduced in human intestines affected by
      inflammatory bowel disease (IBD) and in the gut of mice with DSS-induced colitis.
      IL-21-deficient mice are largely protected against DSS-induced colitis,
      indicating that IL-21 plays a key role in the development of IBD. We previously
      identified a novel IL-21 isoform named IL-21iso. In this study, we found that in
      addition to the conventional IL-21, IL-21iso mRNA was also expressed in the colon
      with DSS-induced colitis. To investigate whether IL-21iso plays a role in DSS
      induced colitis, we established transgenic mice (mIL-21iso-Tg mice) that
      expressed mouse IL-21iso under the control of the lck proximal promoter. Although
      mIL-21iso-Tg mice did not have any gross physical abnormalities, their peripheral
      lymphocytes counts were higher than those in wild-type littermates. Notably,
      their CD8(+) T cell and CD4(+) effector memory T-cell populations were elevated.
      DSS-induced colitis was far more severe in the mIL-21iso-Tg mice than in wild
      type mice, and was accompanied by a marked loss of body weight and by colon
      inflammation with increased cellular infiltration. In DSS-treated mice, colon
      tissues from mIL-21iso-Tg mice had significantly higher gene activation levels
      for cytokines such as IL-17A, TNF-alpha, IL-6, IL-10, and IL-4, and for
      transcription factors such as T-bet, GATA-3, RORgammat, and Foxp3, than were
      found in wild-type mice. These results indicate that besides IL-21, IL-21iso may
      be another regulator of gut inflammation.

PMID- 23557802
TI  - Sociotropic cognition and eating disordered attitudes and behavior in young
      adults.
AB  - Sociotropic cognition is a mindset characterized by a strong need for social
      approval and fear of interpersonal rejection. Sociotropic cognition has been
      associated with depression and health risk behavior in women, but few studies
      have specifically addressed eating disordered attitudes and behaviors, and
      studies including men are lacking. The purpose of the present study was to assess
      the influence of sociotropic cognition on eating-related attitudes and behaviors
      in men and women. Participants were N=362 undergraduate students (51% female;
      mean age=19.2+/-1.43) who completed measures of sociotropic cognition, depressed
      mood, eating disordered attitudes and behaviors, body shape satisfaction, and
      physical activity. Using hierarchical regression, the results demonstrated that
      sociotropic cognition was associated with greater dietary restraint, body shape,
      eating, and weight concerns, emotional eating, and global eating disordered
      score. Body shape dissatisfaction and emotional eating were found to mediate the
      relationship between sociotropic cognition and eating disordered behaviors.
      Sociotropic cognition appears to be an important predictor of body shape
      dissatisfaction and eating disordered behaviors in a non-clinical sample.
      Individuals high in sociotropic cognition may engage in eating disordered
      behavior in response to fears of social evaluation. These findings have
      implications for prevention and treatment of eating disorders. Cognitive
      behavioral intervention strategies are suggested to reduce sociotropic cognition
      and its influence on eating disordered behavior.

PMID- 23557801
TI  - Interleukin 18 (IL18) gene promoter polymorphisms are associated with type 1
      diabetes mellitus in Brazilian patients.
AB  - Interleukin 18 (IL-18) is a cytokine that plays an important role in the Th1
      response, by its ability to induce IFN-gamma production in T cells and natural
      killer cells. Functional variants of IL18 gene has been reported as associated
      with type 1 diabetes (T1D). In the present study were analyzed three promoter
      single nucleotide polymorphisms (SNPs), at -656 (rs1946519), -607 (rs1946518) and
      -137 (rs187238) position, in 181 children and adolescents with T1D and 122
      healthy individuals, both from metropolitan area of Recife, Northeast of Brazil.
      T1D patients were stratified according to the presence autoimmune thyroiditis and
      celiac disease. Allele and genotype frequencies of IL18 SNPs were Hardy-Weinberg
      equilibrium in patients and controls. The allele -137G and the haplotype -656G/
      607C/-137G were more frequent in T1D patients (OR=1.82 and 1.97, respectively)
      then in healthy controls. However, those SNPs were not associated with the age of
      T1D onset as well as with the insurgence of AITD and/or CD in concomitant with
      T1D patients. Our findings suggest an association between IL18 promoter SNPs and
      susceptibility to T1D in Brazilian patients.

PMID- 23557803
TI  - Correlates and associations between weight suppression and binge eating
      symptomatology in a population-based sample.
AB  - Weight suppression (WS), the discrepancy between a person's highest ever and
      current body weight, has been found in a number of studies to be associated with
      the onset and maintenance of bulimia nervosa (BN). The current theories on the
      working mechanism hypothesize that individuals with BN might be caught in a
      (psycho)biobehavioral bind and suggest a circle of weight loss, weight
      suppression, weight gain, and binge eating that in theory should also apply to a
      broad spectrum of binge eating symptomatology. This study was intended to test
      the hypothesis that WS predicts current binge eating with a loss of control
      (BE+LOC) in a population-based sample. We used a population-sample of
      participants (N=3,512) who responded to a survey in a women's magazine. In a
      logistic regression analysis, WS did not predict current BE+LOC, in contrast to
      high diet activity in the past year. Possible explanations for the lack of
      association are discussed. Future studies are needed to specify the specific
      active ingredients in the relation between WS and BN.

PMID- 23557804
TI  - Anxiety as a consequence of modern dietary pattern in adults in Tehran--Iran.
AB  - Food intake patterns in relation to mental health have already been revealed. To
      investigate the relationship between processed food consumption behavior and
      anxiety disorder, a cross sectional study was conducted. Overall, 1782 young
      adults aged 18-35 years were randomly selected using cluster sampling method from
      22 districts of Tehran-Iran in 2011. Diet assessment was done using a 24 hour
      recall questionnaire in two times with a week interval. Anxiety level was
      determined using the validated Speilburger test (Persian version). A proportional
      odds regression model was used to assess the effect of processed food consumption
      on anxiety variables. A significant statistical difference was found between men
      and women in terms of processed food consumption (p<0.001). Adjusting for age,
      total calorie intake, gender, body mass index, socioeconomic status, and history
      of sedative drug consumption as well as mental health disorders, the proportional
      odds regression model showed a significant relationship between increased
      consumption of processed foods and anxiety (OR=4.73, 95% CI: 2.89-12.54 for state
      and OR=4.91, 95% CI: 2.88-13.99 for trait). Identification, modification and
      adjusting incorrect food patterns in the community could be considered as
      valuable steps to turn down nutritional-based health difficulties.

PMID- 23557805
TI  - Validation of an existing measure of eating disorder risk for use with early
      adolescents.
AB  - This study tested a brief eating disorder risk measure, originally developed for
      use with college students, in young adolescents. The measure is called the COEDS
      (College Eating Disorders Screen) and is constructed of items written in everyday
      language used by youth to discuss weight issues, rather than in the language of
      symptom assessment. A sample of 246 early adolescents (mean age, 13) completed
      questionnaire measures of puberty, eating disorder behavior, and eating disorder
      risk two times in a 12-month span. We found that: (a) the COEDS was internally
      consistent; (b) COEDS scores were stable across one year; and (c) COEDS scores
      predicted restricting and compensatory behavior one year later, above and beyond
      prediction from sex, race, prior restricting and compensatory behavior, and prior
      BMI. The COEDS appears to be a reliable and valid measure for risk assessment in
      youth; it may prove useful for researchers and clinicians interested in screening
      for risk and as a means to test whether prevention efforts have reduced risk.

PMID- 23557807
TI  - Vitamin D, bone mineral density and body mass index in eating disorder patients.
AB  - AIM: To investigate associations of vitamin D with BMD and BMI in ED patients.
      METHODS: Vitamin D, BMD and BMI for 50 patients admitted to a specialised ED
      inpatient unit were measured. Patients were aged 15-54 years with BMI 8-25
      kg/m(2). RESULTS: Of the patients, 18% were vitamin D deficient. There was a
      significant linear relationship between vitamin D and BMD T-score at the lumbar
      spine (p=0.029), femoral neck (p<0.001) and total hip (p=0.001). There was no
      relationship between vitamin D and BMI. There was a significant linear
      relationship between BMI and BMD T-score at the lumbar spine (p<0.001), femoral
      neck (p=0.008) and total hip (p=0.001). CONCLUSIONS: Low vitamin D and low BMI
      are associated with low BMD in ED patients. Despite widespread belief that it is
      not necessary, our findings suggest it is appropriate to measure vitamin D in ED
      patients. It should not be assumed ED patients take supplements.

PMID- 23557806
TI  - Predicting premature termination of hospitalised treatment for anorexia nervosa:
      the roles of therapeutic alliance, motivation, and behaviour change.
AB  - OBJECTIVES: This study aims to investigate treatment drop-out, and the associated
      roles of motivation, alliance, and behaviour change exhibited over the first four
      weeks of hospitalised treatment for anorexia. METHODS: 90 participants meeting
      DSM-IV criteria for anorexia nervosa completed questionnaires at admission, and
      four weeks into treatment. Weight data was collected over this same time period.
      At the end of treatment, participants were categorised into completer or
      premature termination groups. RESULTS: The overall rate of premature termination
      was 57.8%. Those who prematurely terminated treatment demonstrated lower
      discharge BMI (p<.0005), and weight gain (p<.0005) than those who completed.
      Therapeutic alliance proved significantly different between outcome groups at
      admission (p=.004). DISCUSSION: End-of-treatment outcomes for those who do not
      complete treatment are invariably poor. Therapeutic alliance appears to be a
      particularly important factor in this area.

PMID- 23557808
TI  - Obesity has few effects on future psychosocial functioning of adolescents.
AB  - We reexamine the effects of obesity on a wide range (n=17) of indicators of
      functioning drawn from five broad domains: interpersonal problems, psychological
      problems, suicidal behaviors, academic performance, and psychiatric disorders.
      Evidence on this question is mixed. Data are analyzed from a large community
      sample of adolescents 11-17 at baseline (n=4175) who were followed up a year
      later (n=3134). Using measured height and weight, overweight was defined as
      95th>BMI<=85th percentile and obese as BMI >95th percentile. At baseline, obesity
      was associated with increased odds only for any mood disorder and poor perceived
      mental health. For boys, there were no significant associations, but girls had
      higher odds of problems at school, poor perceived mental health, and mood
      disorders. Results from the two-wave cohort reveal obesity increased future risk
      only for poor perceived mental health. For boys, the same pattern was observed,
      but for girls there were no significant associations. Overall, we found that
      weight status had few deleterious effects on adolescent social functioning, in
      multivariate, prospective analyses. If there is an effect of obesity on
      functioning, it may operate through mediators such as body image.

PMID- 23557809
TI  - Weight pressures in sport: examining the factor structure and incremental
      validity of the weight pressures in sport - females.
AB  - Due to pressures within the sport environment, such as from coaches, teammates,
      uniforms and judges, female athletes may develop unhealthy eating practices to
      lose weight or change their body size/shape to become more competitive and meet
      societal and sport-related physique ideals. However, up until the development of
      the Weight Pressures in Sport for Females (WPS-F; Reel, SooHoo, Petrie,
      Greenleaf, & Carter, 2010) there was no way to quantify sport-specific weight
      pressures with female athletes. In this study, the psychometric properties of the
      scale were further examined using a sample of 414 female collegiate athletes.
      Sample 1 [n=207; M=19.27 years; SD=1.16] and Sample 2 [n=207; M=19.19 years;
      SD=1.66] participants were of a similar age and were used for exploratory and
      confirmatory analyses respectively. A two factor structure was confirmed and it
      was established that the scale was unique from general sociocultural pressures
      that all women experience, predicting female athletes' internalization, body
      dissatisfaction, dietary intent, and bulimic symptomatology. Specifically, the
      following factors, Coach and Sport Pressures about Weight (Factor 1) and
      Pressures Regarding Appearance and Performance (Factor 2), were found to have
      strong internal consistency and the emerging reliable and valid WPS-F has
      practical implications for screening and identifying weight-related sport
      pressures within female athletes. WPS-F can also serve to educate sport
      professionals about environmental pressures so that disordered eating and body
      image disturbances can be prevented.

PMID- 23557810
TI  - Social anxiety and disordered overeating: an association among overweight and
      obese individuals.
AB  - OBJECTIVE: The study objectives were to evaluate the relationship between social
      anxiety, binge eating, and emotional eating in overweight and obese individuals
      and to evaluate the relationship between weight and social anxiety. METHODS:
      Using an internet based survey, overweight and obese men and women (n=231; mean
      age=36.0+/-12.8; mean BMI=33.7 kg/m(2)+/-6.7) completed several self-report
      measures including: social anxiety, social physique anxiety, binge eating, and
      emotional eating. The relationships among variables were evaluated using
      Spearman's correlations, ANOVAs, and linear and logistic regression equations.
      RESULTS: Clinically significant levels of social anxiety were reported in 59% of
      participants, and binge eating disorder criteria were met by 13%. Social anxiety
      was significantly associated with binge eating (r=.36; OR=1.06, CI=1.02-1.10) and
      emotional eating (r=.46; beta=0.36), but was not associated with restrained
      eating. The association between social physique anxiety and emotional and binge
      eating did not remain significant in regression equations. BMI was associated
      with binge eating (r=.19) but not emotional eating. Level of social anxiety was
      not significantly higher among extremely obese participants, compared to
      overweight and obese participants. CONCLUSIONS: In this study, social anxiety was
      associated with binge eating and emotional eating in overweight and obese men and
      women. When appropriate, interventions could address social anxiety as a barrier
      to normative eating patterns and weight loss.

PMID- 23557811
TI  - Acute and chronic effects of gum chewing on food reinforcement and energy intake.
AB  - Although chewing gum has been considered a potential method for reducing energy
      intake, little empirical data exist to support this idea. The purpose of this
      study was to test the hypothesis that chewing gum before eating reduces
      motivation to eat, hunger, and energy intake. In order to test this hypothesis,
      we conducted two experiments in which participants chewed gum prior to completing
      a food reinforcement task or before all eating occasions for two of three weeks.
      In Experiment 1, we found that chewing gum had no influence on the reinforcing
      value of food, but chewing mint gum reduced liking of and energy intake from
      fruit. In addition, chewing gum reduced self-reported hunger immediately after
      gum chewing and after eating compared with the no gum condition. In Experiment 2,
      gum chewing had no significant effect on total energy intake, but participants
      consumed fewer meals, consumed more energy per meal, and had a lower nutrient
      adequacy ratio during the gum chewing weeks. These studies provide no evidence
      that acute or chronic gum chewing reduces hunger or energy intake. In fact,
      chewing mint-flavored gum may deter consumption of fruit and reduce diet quality.

PMID- 23557812
TI  - Relationship between eating pathology, body dissatisfaction and depressive
      symptoms among male and female adolescents in the United Arab Emirates.
AB  - Research in the field of eating disorders remains limited in the Arab world. The
      cross-sectional study addressed this gap by examining eating disturbances and
      related problem behaviors among 361 (284 females, 77 males) undergraduates in the
      United Arab Emirates (UAE). Standardized measures were used to assess the
      relationship between symptoms of eating pathology, body dissatisfaction and
      depression. Three quarters (73%) of the sample indicated body dissatisfaction
      (78% of females, 58% of males) and 20% scored above the clinical cutoff on the
      eating pathology scale (20% of females, 22% of males). Depressive symptomatology
      predicted significantly higher levels of eating pathology in both genders. The
      findings highlight that eating disturbances and body dissatisfaction are of
      concern among adolescents in the UAE. Local eating disorders prevention
      strategies should address the needs of both females and males and consider
      potential depressive co-morbidity.

PMID- 23557815
TI  - Testing the perfectionism model of binge eating in mother-daughter dyads: a mixed
      longitudinal and daily diary study.
AB  - The perfectionism model of binge eating is an integrative model explaining why
      perfectionism is tied to binge eating. This study extended and tested this
      emerging model by proposing daughters' socially prescribed perfectionism (i.e.,
      perceiving one's mother is harshly demanding perfection of oneself) and mothers'
      psychological control (i.e., a negative parenting style involving control and
      demandingness) contribute indirectly to daughters' binge eating by generating
      situations or experiences that trigger binge eating. These binge triggers include
      discrepancies (i.e., viewing oneself as falling short of one's mother's
      expectations), depressive affect (i.e., feeling miserable and sad), and dietary
      restraint (i.e., behaviors aimed at reduced caloric intake). This model was
      tested in 218 mother-daughter dyads studied using a mixed longitudinal and daily
      diary design. Daughters were undergraduate students. Results largely supported
      hypotheses, with bootstrapped tests of mediation suggesting daughters' socially
      prescribed perfectionism and mothers' psychological control contribute to binge
      eating through binge triggers. For undergraduate women who believe their mothers
      rigidly require them to be perfect and whose mothers are demanding and
      controlling, binge eating may provide a means of coping with or escaping from an
      unhealthy, unsatisfying mother-daughter relationship.

PMID- 23557813
TI  - Individual differences in the relationship between ovarian hormones and emotional
      eating across the menstrual cycle: a role for personality?
AB  - Within-person changes in estradiol and progesterone predict changes in binge
      eating tendencies across the menstrual cycle. However, all women have menstrual
      cycle fluctuations in hormones, but few experience binge eating. Personality
      traits may be critical individual difference factors that influence who will
      engage in emotional eating in the presence of a vulnerable hormonal environment.
      Women (N=239) provided self-reports of emotional eating and saliva samples for
      hormone measurement for 45 consecutive days. Negative urgency and negative
      emotionality were measured once and were examined as moderators of hormone
      emotional eating associations. Consistent with prior research, within-person
      changes in the interaction between estradiol and progesterone predicted emotional
      eating. Neither negative urgency nor negative emotionality interacted with
      changes in estradiol and progesterone to predict changes in emotional eating.
      Additional factors, other than the two personality traits examined, may account
      for individual differences in within-person associations between hormones and
      emotional eating.

PMID- 23557814
TI  - Readability and comprehension of self-report binge eating measures.
AB  - The validity of self-report binge eating instruments among individuals with
      limited literacy is uncertain. This study aims to evaluate reading grade level
      and multiple domains of comprehension of 13 commonly used self-report assessments
      of binge eating for use in low-literacy populations. We evaluated self-report
      binge eating measures with respect to reading grade levels, measure length,
      formatting and linguistic problems. RESULTS: All measures were written at a
      reading grade level higher than is recommended for patient materials (above the
      5th to 6th grade level), and contained several challenging elements related to
      comprehension. Correlational analyses suggested that readability and
      comprehension elements were distinct contributors to measure difficulty.
      Individuals with binge eating who have low levels of educational attainment or
      limited literacy are often underrepresented in measure validation studies.
      Validity of measures and accurate assessment of symptoms depend on an
      individual's ability to read and comprehend instructions and items, and these may
      be compromised in populations with lower levels of literacy.

PMID- 23557816
TI  - Greater energy reduction in 6-n-propylthiouracil (PROP) super-tasters as compared
      to non-tasters during a lifestyle intervention.
AB  - Little is known as to how 6-n-propylthiouracil (PROP) taster status may influence
      changes in dietary intake in adults participating in a lifestyle intervention to
      assist with reducing weight. This secondary data analysis examined changes in
      energy, percent energy from macronutrients, and food group intake; physical
      activity; and body mass index (BMI) in super-tasters and non-tasters
      participating in two randomized controlled trials implementing a lifestyle
      obesity intervention. One trial focused on lowering energy density of the diet
      and the other trial focused on changing eating frequency. Overweight and obese
      participants (n = 57) who completed measures of dietary intake, physical
      activity, and anthropometrics at 0 and 3 months were included in the analyses.
      Taster status was determined at baseline: 46 non-tasters and 11 super-tasters.
      After controlling for condition assignment and baseline values, results indicated
      that a significantly greater reduction in energy intake occurred for super
      tasters as compared to non-tasters (-1149 +/- 561 kcal/day vs. -902 +/- 660
      kcal/day, p < 0.05). No other significant differences in changes in dietary
      intake, physical activity, or BMI were found. These results suggest that in
      situations of reducing energy intake, overweight and obese super-tasters may be
      more successful than overweight and obese non-tasters. More research is needed to
      understand the influence of taster-status on dietary change during a lifestyle
      intervention and how this may impact weight loss.

PMID- 23557817
TI  - Help-seeking intentions in college students: an exploration of eating disorder
      specific help-seeking and general psychological help-seeking.
AB  - This study investigated help-seeking intentions for eating disorders and general
      psychological problems in college students. Participants reported that they would
      be more likely to seek help for a friend with an eating disorder than for
      themselves if they were experiencing an eating disorder. Multiple factors (i.e.,
      sex, year in college, knowledge of eating disorders, and knowledge of available
      resources) were assessed to determine the prediction of help-seeking intentions.
      Only the knowledge of eating disorders significantly predicted whether or not a
      student would be willing to seek help for a friend with a general psychological
      disorder. None of these factors predicted willingness to seek help for friends
      with an eating disorder.

PMID- 23557818
TI  - The relationships among psychiatric medications, eating behaviors, and weight.
AB  - To help address gaps in information about the links that exist between
      psychiatric medications and weight changes, an investigation of relationships
      among select psychotropic agents (i.e., mood stabilizers, antidepressants, and
      second-generation antipsychotics {SGAs}), eating behaviors, and weight was
      conducted. Data from a cross-sectional study of food habits in 97 individuals
      with mood disorders was used. Variables measured included use of psychotropic
      agents, measures of cognitive dietary restraint and disinhibition from the Three
      Factor Eating Behavior Questionnaire (TFEQ), psychiatric functioning, reported
      weight gain and measured BMI. The TFEQ measures were compared to population
      norms. Bivariate and multivariate analyses examined the relationships among the
      psychotropic agents, eating behaviors, and weight. Indicators of cognitive
      dietary restraint and disinhibition were higher than population norms (p's<0.05
      to 0.0001). Depression was associated with restraint (rho=0.21, p<0.05). BMI was
      associated with disinhibition (p<0.05); antidepressant use appeared to moderate
      weight for those taking SGAs and mood stabilizers (p<0.05). Exploration of the
      interacting mechanisms of psychotropic agents and attention to eating attitudes
      and behaviors of individuals taking psychiatric medications might lessen
      pharmaceutical-induced weight gain. Prospective research on large samples that
      can make comparisons to those who are untreated is needed.

PMID- 23557819
TI  - Disordered eating behaviors and sleep disturbances.
AB  - The aim of the present study was to investigate if disordered eating behaviors
      predicted the development of sleep disturbances. A total of 870 students
      participated at baseline, 592 one year later (T1) and 305 two years later (T2).
      The Eating Attitudes Test-40 was used to assess global disordered eating
      behaviors, dietary concerns (DC), bulimic behaviors (BB) and social pressure to
      eat (SPE). Sleep disturbances were assessed by two items related to difficulties
      initiating sleep (DIS) and maintaining sleep (DMS). A sleep disturbance index
      (SDI) was calculated by summing DIS and DMS scores. Results revealed that global
      disordered eating behaviors at baseline predicted DIS, DMS and SDI at T1 and T2.
      Students with increased BB and SPE scores at baseline were more likely to
      experience sleep onset and sleep maintenance difficulties in the long term. These
      results suggest that assessment and correction of eating behaviors might prevent
      sleep disturbances.

PMID- 23557820
TI  - An open-label efficacy trial of escitalopram for night eating syndrome.
AB  - OBJECTIVE: Night eating syndrome (NES) has become increasingly recognized as a
      disorder in need of effective treatments. Selective serotonin reuptake inhibitors
      have shown efficacy in previous trials, so we sought to expand our understanding
      of the efficacy of escitalopram in the current trial. METHOD: Thirty-one adults
      with NES participated in a 12-week open-label trial of escitalopram. Outcome
      measures included the Night Eating Symptom Scale (NESS), percent of daily intake
      after the evening meal (% intake) and number of nocturnal ingestions/week (NI),
      weight, total awakenings/week, mood, and quality of life. Mixed-effects models
      were used to assess change over time. RESULTS: Significant reductions were
      observed from week 0 to week 12 for the NESS (30.2 to 15.2), % intake (46% to
      17%), NI (5.8 to 1.2), weight (90.2 to 88.6 kg), awakenings (8.1 to 2.7), and BDI
      II (12.1 to 7.7). Outcomes did not differ significantly by gender, age, race, or
      psychiatric co-morbidity status. Eighteen of 31 completed 12 weeks of treatment.
      DISCUSSION: This open-label trial of escitalopram showed significant reductions
      in symptoms associated with NES. Randomized controlled trials are warranted to
      test these findings. TRIAL REGISTRATION: clinicaltrials.gov identifier:
      NCT01401595.

PMID- 23557821
TI  - Differences in appearance-related commentary, body dissatisfaction, and eating
      disturbance among college women of varying weight groups.
AB  - This study examined appearance-related commentary, body dissatisfaction, and
      eating disturbance in 924 undergraduate females. Significant group differences
      were found in type of appearance-related commentary received across weight
      groups. Overweight and obese women experienced negative weight and shape-related
      comments at greater frequencies and positive weight and shape-related comments at
      lower frequencies compared to underweight and normal weight women. A higher
      frequency of positive weight and shape-related commentary was associated with
      less body dissatisfaction for all women and less shape and weight concerns for
      obese women. These findings suggest that the weight status of young women likely
      influences the appearance-related commentary that they receive and the manner in
      which such commentary affects their body image and eating behaviors.

PMID- 23557822
TI  - Self-compassion in the face of shame and body image dissatisfaction: implications
      for eating disorders.
AB  - The current study examines the role of self-compassion in face of shame and body
      image dissatisfaction, in 102 female eating disorders' patients, and 123 women
      from general population. Self-compassion was negatively associated with external
      shame, general psychopathology, and eating disorders' symptomatology. In women
      from the general population increased external shame predicted drive for thinness
      partially through lower self-compassion; also, body image dissatisfaction
      directly predicted drive for thinness. However, in the patients' sample increased
      shame and body image dissatisfaction predicted increased drive for thinness
      through decreased self-compassion. These results highlight the importance of the
      affiliative emotion dimensions of self-compassion in face of external shame, body
      image dissatisfaction and drive for thinness, emphasising the relevance of
      cultivating a self-compassionate relationship in eating disorders' patients.

PMID- 23557823
TI  - Why do eating disorders and obsessive-compulsive disorder co-occur?
AB  - The purpose of this study was to use an alternative, dimensionally based approach
      to understanding the reasons for comorbidity between eating disorders and
      obsessive-compulsive disorder. Participants from a representative community
      sample (N=407; 47% female) completed self-report measures of eating pathology,
      obsessive-compulsive symptoms, perfectionism, and neuroticism. Hierarchical
      multiple regression indicated that neuroticism and perfectionism completely
      mediated associations between most obsessive-compulsive and eating disorder
      symptoms. However, body dissatisfaction shared unique associations with checking,
      cleaning, and obsessive rituals that could not be explained by these personality
      traits. Results suggest that shared personality traits play a key role in the
      comorbidity between eating disorders characterized by binge eating and dietary
      restraint and obsessive-compulsive disorder. Future studies are needed to examine
      whether similar underlying neurocognitive processes that give rise to compulsive
      checking, cleaning, and obsessive rituals may also contribute to the development
      and maintenance of body checking in individuals diagnosed with eating disorders.

PMID- 23557824
TI  - Validation of the Yale Food Addiction Scale among a weight-loss surgery
      population.
AB  - The Yale Food Addiction Scale (YFAS), recently validated in college students and
      binge eaters, is a means to assess "food addiction" in accordance with DSM-IV
      criteria for substance dependence. Using online survey methodology, we aimed to
      validate the use of the YFAS among weight loss surgery (WLS) patients.
      Participants completed measures about pre-WLS food addiction (YFAS), emotional
      and binge eating, behavioral activation and inhibition, and pre- and post-WLS
      substance use. A sample of 67 WLS patients (59.7% Roux-en-Y) was recruited;
      participants were 62.7% female, 86.6% Caucasian, had a mean age of 42.7; and
      53.7% met the criteria for pre-WLS food addiction. Convergent validity was found
      between the YFAS and measures of emotional eating (r=.368, p<.05) and binge
      eating (r=.469, p<.05). Discriminant validity was supported in that problematic
      substance use, behavioral activation, and behavioral inhibition were not
      associated with YFAS scores. Incremental validity was supported in that the YFAS
      explained a significant proportion of additional variance in binge eating scores,
      beyond that predicted by emotional eating (EES) and disordered eating behavior
      (EAT-26). Those meeting the food addiction criteria had poorer percent total
      weight loss outcomes (32% vs. 27%). There was a nonsignificant trend towards
      those with higher food addiction being more likely to admit to post-WLS
      problematic substance use (i.e., potential "addiction transfer"; 53% vs. 39%).
      Results support the use of the YFAS as a valid measure of food addiction among
      WLS patients. Future research with a larger sample may shed light on potentially
      important relationships between pre-surgical food addiction and both weight and
      substance use outcomes.

PMID- 23557825
TI  - Measurement of disordered eating in Latina college women.
AB  - The Eating Disorder Risk Composite (EDRC) comprises the Drive for Thinness,
      Bulimia, and Body Dissatisfaction subscales of the Eating Disorder Inventory,
      Third Edition (EDI-3, Garner, 2004). Past research conducted with Latina college
      women (LCW) has found older versions of the EDRC subscales to be reliable, but
      the EDI-3's EDRC factor structure has yet to be studied among LCW. The present
      study investigated the pattern of responses to and the factor structure of the
      EDRC in LCW. It was hypothesized that eating pathology would be present and that
      a factor analysis would find some discrepancies between the original factor
      structure of the EDRC and the factor structure from LCW. Analyses of data on a 6
      point Likert scale indicate that drive for thinness and body dissatisfaction are
      far more prevalent than is bulimic symptomology in LCW. Principal Axis Factoring
      with promax rotation was used to extract three factors very similar to the
      original EDRC. Some discrepancies in the item loadings were observed, most
      notably that half of the items from the original Body Dissatisfaction subscale
      did not load together on one factor. Overall, the EDRC appears to be a good
      measurement of eating- and body-related phenomena among LCW. Implications,
      limitations, and future directions are discussed.

PMID- 23557826
TI  - Evaluating the indirect effect of self-compassion on binge eating severity
      through cognitive-affective self-regulatory pathways.
AB  - Current theory and evidence point to disruptions in self-concept and difficulties
      with emotion regulation as contributing to the severity of binge eating.
      Alternatively, contemporary perspectives on self-compassion suggest that
      individual differences in this adaptive approach to self-regulation may serve to
      counteract these cognitive-affective triggers presumably resulting in reductions
      in binge eating severity. Accordingly, the present cross-sectional analysis
      examined an indirect effect model of positive dimensions of self-compassion on
      binge eating severity through both emotional tolerance and unconditional self
      acceptance pathways. Two hundred fifteen undergraduate students (78% female)
      completed self-report measures of the variables of interest; BMI was calculated
      from self-reported heights and weights. Pearson's correlations revealed a
      positive linear association between self-compassion and unconditional self
      acceptance; negative links were observed between self-compassion and emotional
      intolerance along with the severity of binge eating symptoms. A subsequent
      multiple mediator analysis utilizing both normal test theory and robust non
      parametric bootstrap resampling procedures confirmed the presence of a
      significant total indirect effect of self-compassion on binge eating severity (
      .15, p<0.001) through the combined mediators along with yielding specific
      indirect effects for both emotional tolerance (-.05, p<0.05) and unconditional
      self-acceptance (-.11, p<0.01) which were preserved in a model adjusted for BMI.
      Preliminary results underscore the need to further evaluate the tenability of
      this model in both prospective cohort and intervention-based research. Findings
      additionally invite considering the value of integrating self-compassion training
      into college health promotion efforts towards mitigating the appreciable levels
      of binge eating behavior prevalent in this at-risk population.

PMID- 23557827
TI  - Role of obesity and media in body weight concern among female university students
      in Kuwait.
AB  - The aim of this study was to find out the association of media and obesity status
      with body weight concern among female university students in Kuwait. 228 female
      students, aged 19-25 years, were selected at convenience from the Women's College
      in Kuwait. A previously validated questionnaire was used to collect information
      on the role of media in body concern and how parents, peers and the girls
      themselves perceived girls' body shapes. Weight and height were gathered by self
      reporting. Use of internet and reading women's magazines had a significant impact
      on dieting by the girls to lose weight (P<0.0007 and P<0.0114, respectively). The
      mass media had two to three times more influence on obese girls than non-obese
      girls. Only watching television had a significant impact on girls' body shape
      concern (P<0.053). About 30% of non-obese and 81% of obese girls were
      dissatisfied with their current weight. There were significant differences
      between obese and non-obese girls regarding the girls' views and the views of
      their peers and parents about the body weight of the girls (P<0.000 for all). The
      pressure from peers and parents, in addition to the mass media, may lead to
      disturbed attitudes towards eating among Kuwaiti girls.

PMID- 23557828
TI  - Personality, clinical features, and test instructions can affect executive
      functions in Eating Disorders.
AB  - Cognitive deficits in Eating Disorders have been related to the executive
      function domain. Yet, to date, only few works investigated the relationship
      between neuropsychological and clinical issues, and these studies were separately
      conducted either on Anorexia Nervosa (AN) or Bulimia Nervosa (BN). In this study,
      three groups of AN, BN and matched controls were administered the Trail Making
      Test, the Wisconsin Card Sorting Test, and the Hayling Sentence Completion Test,
      in addition to personality and clinical assessments (Temperament and Character
      Inventory, SCL-90-R, EDI-2). Results from AN indicated a relationship between
      cognitive rigidity and fixed psychological traits. Conversely, BN showed broader
      correlations among slowness, inhibition, and psychopathology-state indexes,
      confirming the clear relation published in the literature. We also hypothesize
      that task peculiar characteristics can affect high-order attentional activities
      in Eating Disorders. In fact, these patients do not differ from controls when the
      examiner provides overt instruction and run-in examples, but they can find
      serious difficulties when the correct rule is to be derived and modified from
      feedbacks during the test, as in the Wisconsin Card Sorting Test. Perfectionist
      stable traits support this hypothesis, especially in AN, as excessive cognitive
      control can either improve or damage set-shifting and decision-making procedures.

PMID- 23557829
TI  - Relationship of dieting and restrained eating to self-reported caloric intake in
      female college freshmen.
AB  - Evidence indicates that restrained eaters do not eat less than unrestrained
      eaters in the natural environment. However, no study has examined caloric intake
      in those who are currently dieting to lose, or avoid gaining, weight. The current
      study examined caloric intake using 24-hour food recalls among individuals
      dieting to lose weight, dieting to avoid weight gain, restrained nondieters, and
      unrestrained nondieters. Participants were 246 female college students
      participating in a weight gain prevention trial. The predicted significant
      difference in caloric intake across the four groups was found for beverage but
      not for food intake. Results reinforce past literature indicating that
      dieting/restraint status does not reflect hypo-caloric intake in naturalistic
      settings.

PMID- 23557830
TI  - Psychometric validation of the Clinical Impairment Assessment in a UK eating
      disorder service.
AB  - A number of studies have provided data on young women for the Clinical Impairment
      Assessment (CIA, v. 3.0), a measure of psychosocial impairment in eating
      disorders. However, little data exists on eating disorder samples. The aim of the
      current study was to investigate psychometric properties of the CIA in a clinical
      sample, using confirmatory factor analysis based on the originally-proposed
      model. The CIA was administered alongside with the Eating Disorder Examination
      (EDE) to 190 individuals referred to an eating disorder service. Psychometric
      properties of the CIA were acceptable, based on model fit and factor loadings.
      The CIA appears to be a useful and valid measure for the assessment of impairment
      in eating disorders.

PMID- 23557831
TI  - The development and test of an intervention to improve ADR screening in nursing
      homes.
AB  - OBJECTIVES: The aim of this study was to develop and test the effect of an
      instrument, Pharmanurse, to facilitate nurse-driven adverse drug reaction (ADR)
      screening as an input for interdisciplinary medication review in nursing homes.
      DESIGN: Intervention study with a pre-posttest design PARTICIPANTS: All residents
      of a convenience sample of 8 nursing homes of more than 80 beds were eligible if
      they resided at least 1 month in the nursing home and took 4 or more different
      medications. Residents receiving palliative care were excluded. INTERVENTION: The
      intervention consisted of interdisciplinary medication review, prepared by nurse
      observations of potential ADRs using personalized screening lists generated by
      the Pharmanurse software. Pharmanurse is specifically adapted to use by nurses
      and to use in nursing homes. MEASUREMENTS: Outcome parameters were the number of
      ADRs detected by nurses, ADRs confirmed by general practitioners, and medication
      changes. After the intervention, health care professionals involved completed a
      questionnaire to evaluate the value and the feasibility of the intervention.
      RESULTS: Nurses observed 1527 potential ADRs in 81% of the 418 residents (mean
      per resident 3.7). Physicians confirmed 821 ADRs in 60% of the residents (mean
      per resident 2.0). As a result, 214 medication changes were planned in 21% of the
      residents (mean per resident 0.5) because of ADRs. Health care professionals gave
      the Pharmanurse intervention a score of 7 of 10 for the potential to improve
      pharmacotherapy and 83% of the physicians were satisfied about nurses' screening
      for ADRs. CONCLUSIONS: The Pharmanurse intervention supports nurses in ADR
      screening and may have the potential to improve pharmacotherapy.

PMID- 23557832
TI  - Replication dynamics: biases and robustness of DNA fiber analysis.
AB  - The factors that govern replication programs are still poorly identified in
      metazoans, especially in mammalian cells. Thanks to molecular combing, the
      dynamics of DNA replication can be assessed at the genome-scale level from the
      cumulative analysis of single DNA fibers. This technique notably enables
      measurement of replication fork speed and fork asymmetry and that of distances
      separating either initiation or termination events. The results presented here
      aim to evaluate requirements critical to accurate measurement of replication
      parameters by molecular combing. We show that sample size, fiber length and DNA
      counterstaining are crucial to gain robust information concerning replication
      dynamics. Our results thus provide a methodological frame to investigate the DNA
      replication program through molecular combing analyses. 

PMID- 23557833
TI  - Nanobodies raised against monomeric alpha-synuclein distinguish between fibrils
      at different maturation stages.
AB  - Nanobodies are single-domain fragments of camelid antibodies that are emerging as
      versatile tools in biotechnology. We describe here the interactions of a specific
      nanobody, NbSyn87, with the monomeric and fibrillar forms of alpha-synuclein
      (alphaSyn), a 140-residue protein whose aggregation is associated with
      Parkinson's disease. We have characterized these interactions using a range of
      biophysical techniques, including nuclear magnetic resonance and circular
      dichroism spectroscopy, isothermal titration calorimetry and quartz crystal
      microbalance measurements. In addition, we have compared the results with those
      that we have reported previously for a different nanobody, NbSyn2, also raised
      against monomeric alphaSyn. This comparison indicates that NbSyn87 and NbSyn2
      bind with nanomolar affinity to distinctive epitopes within the C-terminal domain
      of soluble alphaSyn, comprising approximately amino acids 118-131 and 137-140,
      respectively. The calorimetric and quartz crystal microbalance data indicate that
      the epitopes of both nanobodies are still accessible when alphaSyn converts into
      its fibrillar structure. The apparent affinities and other thermodynamic
      parameters defining the binding between the nanobody and the fibrils, however,
      vary significantly with the length of time that the process of fibril formation
      has been allowed to progress and with the conditions under which formation
      occurs, indicating that the environment of the C-terminal domain of alphaSyn
      changes as fibril assembly takes place. These results demonstrate that nanobodies
      are able to target forms of potentially pathogenic aggregates that differ from
      each other in relatively minor details of their structure, such as those
      associated with fibril maturation. 

PMID- 23557835
TI  - Non-lifting sign from cold biopsy of sessile serrated polyp.

PMID- 23557834
TI  - Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a
      systematic review and indirect comparison.
AB  - BACKGROUND: Severe allergic rhinitis uncontrolled by pharmacotherapy can
      adversely affect quality of life. Both subcutaneous immunotherapy (SCIT) and
      sublingual immunotherapy (SLIT) have demonstrated effectiveness in this patient
      group; however, it remains uncertain which route of administration is more
      effective. OBJECTIVES: We sought to update existing systematic reviews on the
      clinical effectiveness of SCIT and SLIT versus placebo, to undertake a systematic
      review of head-to-head trials, and to compare the relative effectiveness of SCIT
      and SLIT in an adjusted indirect comparison. METHODS: Standard systematic review
      methods aimed at minimizing bias were used. Double-blind, randomized, placebo
      controlled trials of SCIT or SLIT or trials of SCIT versus SLIT were included.
      Meta-analysis and indirect comparison meta-analysis with meta-regression were
      performed. RESULTS: Updated meta-analyses confirmed statistically significant
      benefits for SCIT and SLIT compared with placebo in adults and, to a lesser
      extent, in children. Only 1 head-to-head trial met the inclusion criteria; both
      this and the indirect comparisons did not provide conclusive results in favor of
      either SCIT or SLIT based on symptom-medication or quality-of-life scores. There
      was a trend toward favoring SCIT for symptom and medication scores. CONCLUSIONS:
      Although there is clear evidence of effectiveness of both SCIT and SLIT,
      superiority of one mode of administration over the other could not be
      consistently demonstrated through indirect comparison, and further research is
      needed to establish the comparative effectiveness of SCIT versus SLIT.

PMID- 23557836
TI  - Gastric carcinoma with lymphoid stroma resembling a hypoechoic submucosal tumor.

PMID- 23557837
TI  - High prevalence of Behcet's disease in southern Italy.
AB  - OBJECTIVES: This paper aims to estimate the prevalence of Behcet's disease (BD)
      in the city of Potenza, the regional capital of Basilicata (or Lucania) Region,
      in southern Italy. METHODS: Patients with BD living in Potenza for at least 12
      months prior to diagnosis were identified through the following sources: general
      practitioners, community-based specialists, San Carlo Hospital specialists, the
      Basilicata centralised index and the Basilicata database for rare diseases. All
      identified patients were contacted by phone and were recalled to our outpatient
      clinic for re-evaluation. Patients were classified as having complete BD if they
      met the International Study Group (ISG) criteria for BD. RESULTS: By surveying a
      population of 69.060 subjects, 13 patients with a diagnosis of BD were
      identified. All were white and Italian by descendent. Eleven out of these
      satisfied the ISG criteria and allowed us to obtain a prevalence rate of 15.9 per
      100.000 (95%CI 8.9-28.5), which is the highest ever found value in Europe.
      CONCLUSIONS: This cross-sectional population-based study suggests that BD is more
      frequent in the southern part than in the northern part of Italy and confirms
      that the prevalence of the disease increases in a north-to-south manner within
      the European continent.

PMID- 23557838
TI  - Origins of house reinfestation with Triatoma infestans after insecticide spraying
      in the Argentine Chaco using wing geometric morphometry.
AB  - Identifying the origins of insect vectors collected after community-wide residual
      insecticide applications is a relevant challenge in the Gran Chaco region where
      the main vector of Chagas disease Triatoma infestans usually reinfests human
      dwellings. Wing geometric morphometry was used to compare the right wings of 63
      males and 54 females collected at 4 months post-spraying (MPS) with those from
      165 males and 111 females collected before full-coverage spraying with
      pyrethroids in a well-defined rural area in Northeastern Argentina. Male and
      female wing centroid size resulted significantly larger at 4MPS than before
      interventions, but no significant changes in shape were detected. Metric
      disparity (variance of shape) varied significantly in males but not in females.
      Using shape variables, a relatively large fraction of post-spraying males (70%)
      and females (54%) could not be differentiated from those collected at the same
      source house or at the nearest infested house before interventions. Bugs
      collected at 4 and 8MPS in a persistently infested house were mainly assigned to
      the source house. These results support the hypothesis of persistent bug
      populations that survived the insecticide application at local spatial scales,
      and are consistent with the occurrence of vector control failures most likely
      related to moderate pyrethroid resistance. Wing geometric morphometry is a useful
      tool for identifying sources of reinfestation, but it is limited by the spatial
      structure found in the reference populations. Combined with field and genetic
      data, this approach may contribute to the understanding of the reinfestation
      process and improvement of vector control strategies.

PMID- 23557840
TI  - 1,3,4-Oxadiazol-2-ones as fatty-acid amide hydrolase and monoacylglycerol lipase
      inhibitors: Synthesis, in vitro evaluation and insight into potency and
      selectivity determinants by molecular modelling.
AB  - Inhibition of the key hydrolytic enzymes of the endocannabinoid system, fatty
      acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been proposed
      as potential mode of action for various therapeutic applications. Continuing our
      previous work, we take the first steps of structure-activity relationship
      exploration and show that 1,3,4-oxadiazol-2-ones can serve as scaffold for both
      selective FAAH and MAGL inhibitors, and also function as a dual FAAH/MAGL
      inhibitor at sub-micromolar IC50 values. Moreover, 10-fold selectivity against
      MAGL over FAAH was achieved with compound 3d (FAAH and MAGL IC50; 2.0 and 0.22
      MUM). Lastly, enzyme and ligand features contributing to the potency and
      selectivity differences are analysed by molecular docking.

PMID- 23557839
TI  - Population genetics, sequence diversity and selection in the gene encoding the
      Plasmodium falciparum apical membrane antigen 1 in clinical isolates from the
      south-east of Iran.
AB  - The Plasmodium falciparum apical membrane antigen1 (AMA1) is a leading malaria
      vaccine candidate antigen. In the present investigation, for the first time, the
      almost full length of the ama1 gene covering domain I (DI), DII and DIII was PCR
      amplified and sequenced in 21 P. falciparum isolates collected from the
      southeastern parts of Iran. The result showed the low genetic diversity of
      Iranian PfAMA1 with 11 PfAMA1 haplotypes in which nine out of 11 haplotypes are
      novel and have been reported for the first time. The Iranian P. falciparum
      population indicated a moderate level of genetic differentiation. The difference
      among the rates of non-synonymous and synonymous mutations, Tajima's D and
      McDonald-Kreitman tests suggested that the diversity at DI is due to positive
      natural selection. In addition, recombination contributes to the diversity of
      Iranian PfAMA1 and this is supported by the decline of the linkage disequilibrium
      index R(2) with increasing the nucleotide distance. The highly polymorphic
      residues (positions: 187, 197, 200, 230 and 243) were polymorphic; however, most
      of the SNPs in non-polymorphic residues were conserved except the residue at
      position 395. Nevertheless, no mutation was found in the DII loop of the Iranian
      PfAMA1, indicating that it is subjected to purifying selection. In conclusion,
      the low genetic diversity in PfAMA1 among Iranian isolates supports and provides
      valuable information for the development of a PfAMA1-based malaria vaccine.

PMID- 23557841
TI  - Early drug development predictions of glass-forming ability and physical
      stability of drugs.
AB  - The purpose of this study was to investigate if rapidly measured physical
      properties can predict glass-forming ability and glass stability of drug
      compounds. A series of 50 structurally diverse drug molecules were studied with
      respect to glass-forming ability and, for glass-formers (n=24), the physical
      stability upon 1 month of storage was determined. Spray-drying and melt-cooling
      were used to produce the amorphous material and the solid state was analysed by
      Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction. Thermal
      properties and molecular weight (Mw) were used to develop predictive models of
      (i) glass-forming ability and (ii) physical stability. In total, the glass
      forming ability was correctly predicted for 90% of the drugs from their Mw alone.
      As a rule of thumb, drugs with Mw greater than 300 g/mole are expected to be
      transformed to its amorphous state by using standard process technology. Glass
      transition temperature and Mw predicted the physical stability upon storage
      correctly for 78% of the glass-forming compounds. A strong sigmoidal relationship
      (R(2) of 0.96) was identified between crystallization temperature and stability.
      These findings have the potential to rationalize decisions schemes for utilizing
      and developing amorphous formulations, through early predictions of glass-forming
      ability from Mw and physical stability from simple DSC characterization.

PMID- 23557842
TI  - Development of solid lipid nanoparticles based controlled release system for
      topical delivery of terbinafine hydrochloride.
AB  - The study describes the development and evaluation of solid lipid nanoparticles
      (SLNs) of terbinafine hydrochloride (TH) for sustained release and skin
      targeting. TH-loaded SLNs were prepared by solvent-injection technique and
      optimized using 3(3) full-factorial design. Effect of drug:lipid ratio,
      surfactant concentration and volume of organic solvent were studied on %
      entrapment efficiency (%EE) and particle size (PS). The optimum formulation based
      on desirability (0.945) exhibited %EE of 73.74% and PS of 300 nm. Optimized SLNs
      were incorporated into Carbopol gel and evaluated for drug content, pH, in vitro
      release, ex vivo retention, in vivo pharmacodynamic and stability studies. Drug
      release from SLNs dispersion followed Korsmeyer-Peppas model, indicating Fickian
      drug release, while that from the gel followed Higuchi model. The ex vivo studies
      through rat abdominal skin indicated skin retention ability of SLNs as compared
      to commercial product. In vivo pharmacodynamic studies showed that the SLNs based
      gel reduced fungal burden of Candida albicans in rats as compared to commercial
      product in shorter duration of time. The SLNs dispersion and gel exhibited
      physicochemical stability under refrigeration upto 3 months. It was concluded
      that SLNs incorporated Carbopol gel had skin targeting ability and may serve as a
      promising carrier in treatment of fungal skin infections.

PMID- 23557843
TI  - Dissolution enhancement of Deflazacort using hollow crystals prepared by
      antisolvent crystallization process.
AB  - Deflazacort (DFZ), a derivate of prednisolone, is a poorly soluble drug which has
      been proposed to have major advantages over other corticosteroids. Poorly soluble
      drugs present limited bioavailability due to their low solubility and dissolution
      rate and several strategies have been developed in order to find ways to improve
      them. In general, pharmaceutical laboratories use a micronized process to reduce
      the particle size in order to increase the dissolution of the drugs. However,
      this process causes changes such as polymorphic transitions, particle
      agglomeration and a reduction in fluidity and wettability. These solid-state
      properties affect the dissolution behavior and stability performance of drugs.
      Crystallization techniques are widely used in the pharmaceutical industry and
      antisolvent crystallization has been used to obtain ultrafine particles. In this
      study, DFZ was investigated in terms of its antisolvent crystallization in
      different solvents and under various preparation conditions (methanol/water
      ratio, stirring and evaporation rate, etc.), in order to compare the
      physicochemical properties between crystallized samples and raw materials
      available on the Brazilian market with and without micronization. Crystalline
      structure, morphology, and particle size, and their correlation with the
      Intrinsic Dissolution Rate (IDR) and dissolution profile as relevant
      biopharmaceutical properties were studied. Crystallization conditions were
      achieved which provided crystalline samples of hollow-shaped crystals with
      internal channels, which increased the dissolution rate of DFZ. The antisolvent
      crystallization process allowed the formation of hollow crystals, which
      demonstrated a better dissolution profile than the raw material (crystalline and
      micronized), making this a promising technique as a crystallization strategy for
      improving the dissolution and thus the bioavailability of poorly soluble drugs.

PMID- 23557844
TI  - Brain correlates of cognitive inhibition in fibromyalgia: emotional intrusion of
      symptom-related words.
AB  - Evidence coming from neuropsychological studies has showed the presence of
      cognitive alterations in fibromyalgia. Such dysfunctions are especially
      remarkable when the set in motion of executive control processes, such as
      inhibition, is required to perform successfully; however, neural data related to
      these mechanisms are very scarce. Present study tried to characterize cognitive
      inhibition mechanisms, as part of the attentional control functions, in patients
      with fibromyalgia. Participants (two groups: fibromyalgia patients and healthy
      control participants) were asked to perform in an emotional Stroop task while
      event-related potentials (ERP) were recorded. Four different emotional
      interference conditions were created: fibromyalgia symptom-related words,
      arousing-negative, arousing-positive and neutral words. Brain activity and
      behavioral data were analyzed. Principal component analyses were employed to
      reliably define ERP components along with a source-estimation technique. Symptom
      related words elicited greater frontal P450 amplitudes and enhanced activation
      within right inferior frontal gyrus as compared to the rest of stimuli. This
      effect was only true for the fibromyalgia group. Behavioral contrasts, however,
      did not produce significant differences. Scalp and source estimation findings
      suggest the presence of a specific difficulty in cognitive inhibition in
      fibromyalgia patients (under conditions intimately linked with the core concerns
      of their disease). Data point to the involvement of right inferior frontal
      cortices in this inefficient mechanism, which might cause an enhanced and
      dysfunctional effort of processing to achieve only a comparable performance to
      healthy people. Implications of these results are discussed. Nevertheless,
      further investigations are needed to better understand dysfunctional cognition in
      fibromyalgia.

PMID- 23557845
TI  - HbA1c targets in type 2 diabetes: guidelines and evidence.
AB  - Type 2 diabetes is defined by chronic hyperglycaemia, decreased insulin secretion
      and increased insulin resistance and is often associated with overweight or
      obesity, hypertension and dyslipidaemia.(1) Aims of treatment include minimising
      long-term complications (e.g. cardiovascular disease, blindness, chronic kidney
      disease, premature mortality) and avoiding unwanted effects of treatment (e.g.
      severe hypoglycaemia, weight gain).(1) Publication of the United Kingdom
      Prospective Diabetes Study (UKPDS) 33 study in 1998 suggested that 'intensive
      blood glucose control' to lower the glycated haemoglobin (HbA1c) in people with
      type 2 diabetes reduced microvascular disease but not macrovascular
      complications.(2) The UKPDS 34 study in overweight patients found that metformin
      produced less of a reduction in HbA1c but reduced cardiovascular complications
      and death.(3) More recently, further trials have examined the impact of intensive
      glycaemic control and have produced conflicting results.(1,4-11) Here we examine
      the evidence and guideline recommendations for HbA1c targets; glycaemic control
      for acutely unwell patients and targets in pregnancy will not be covered.

PMID- 23557846
TI  - Is hyponatremia mistreated? Challenging the current paradigm.
AB  - BACKGROUND: Hyponatremia is a common but often mistreated clinical situation in
      the ICU. This often requires the physician to identify the underlying problem,
      adrenal insufficiency. However, by the textbook, the current treatment always
      involves sodium chloride supplementation to hyponatremic patients, either
      intravenous or oral intake. We hypothesize that the mechanism behind most
      hyponatremia is most likely to be the sodium and water redistribution from the
      serum to the cells or the interstitial spaces due to the insufficient cortical
      steroid, not the sodium deficiency. As we have no reason to believe the patients
      have lost that much sodium which caused hyponatremia. Therefore, giving this type
      of hyponatremic patients (adrenal insufficient) sodium chloride is always
      ineffective and sometimes catastrophic. METHODS: We discuss the possible
      mechanism for hyponatremia in critically ill/post surgery patients who are mostly
      likely to be adrenal insufficient rather than absolute sodium deficiency. In
      combination with many other common but unexplainable symptoms such as nausea,
      vomiting, obstinate diarrhea, hypotension and coma in the ICU, it is highly
      likely that hyponatremia is a condition which reflects the patients' adrenal
      function. The evidence supporting our hypothesis is that, (1) the serum sodium
      level does not always respond well to sodium supplementation therapy; (2) those
      aforementioned symptoms alleviated simultaneously with the serum sodium level
      returned to normal after the hydrocortisone or prednisone was administered
      without any oral/intravenous sodium supplementation; (3) patient with an elevated
      serum/urine cortisol level suffers from aforementioned unexplainable symptoms
      does not warrant him being adrenal sufficient. If the patient also has
      hyponatremia, the diagnosis can be considered as "relative adrenal insufficiency"
      and the patient would respond well to hydrocortisone or prednisone therapy.
      CONCLUSIONS: We hypothesize that hyponatremia without significant loss of sodium
      can be used as an indicator to monitor the patients' adrenal function regardless
      of the serum/urine cortisol level. Furthermore, we propose a novel approach
      toward hyponatremia treatment in critically ill patients would be hydrocortisone
      or prednisone therapy depending on the circumstances.

PMID- 23557847
TI  - Regional pathology in glaucoma--an overlooked link to neuroprotective strategies.
AB  - Primary open-angle glaucoma (POAG) is the second commonest cause of blindness in
      the world. It is a neurodegenerative disease characterized by retinal ganglion
      cell loss. The molecular mechanism leading to glaucoma damage is unclear.
      Understanding the pathways that favor neuronal survival plus those that
      predispose to neuronal demise in POAG may have direct implications for other
      neurodegenerative diseases. POAG is a heterogeneous disease. A small subset of
      POAG patients develop damage in a highly focal form with a discrete sector of the
      optic nerve manifesting well delineated neuronal loss. It is hypothesized that
      this pattern of nerve loss indicates the optic nerve is not molecularly
      homogeneous. Genetic analysis of patients with isolated focal forms of POAG may
      enable new genes to be identified in glaucoma. Finding the responsible genes in
      POAG is a critical first step. The potential implications are earlier disease
      detection with resultant optimized visual preservation. Future treatment options
      could develop that include altered gene regulation, gene silencing or introducing
      repair genes. Determining the molecular causes for regional neuronal
      susceptibility could lead to identification of pathways underlying disease and
      ultimately effective patient-specific neuroprotective strategies.

PMID- 23557848
TI  - Sequential shift of energy production pathways at the fetal stage and during
      lifetime.
AB  - As eukaryotes, human beings spend their lifetime using two different pathways for
      energy production: the anaerobic glycolysis pathway and aerobic mitochondria
      pathway. Energy produced using the glycolysis pathway is utilized for cell
      division and prompt force of white fiber muscles whereas that produced by the
      mitochondria pathway is utilized for suppression of cell division and continuous
      force of red fiber muscles. Herein, it is proposed that there exists a sequential
      shift of energy production pathways at the fetal stage and during the lifetime.
      If we introduce this concept in human biology, then it is may be easy to
      understand the energy requirement characteristics of fetuses, children, adults
      and aged persons. For example, during childhood the glycolysis pathway is more
      predominant than the mitochondria pathway in energy production. Reflecting this
      fact, children grow and extend their height by division of generalized cells of
      the body. To achieve this, they have to eat meals many times a day (more than
      three times a day) due to a less efficient energy production rate in the
      glycolysis pathway. Similarly, the characteristics of adults and aged persons can
      be well described using this concept.

PMID- 23557849
TI  - A serotonin hypothesis of schizophrenia.
AB  - Chronic widespread stress-induced serotonergic overdrive in the cerebral cortex
      in schizophrenia, especially in the anterior cingulate cortex (ACC) and
      dorsolateral frontal lobe, is the basic cause of the disease. The concept of
      excessive serotonergic stimulation is supported by NMR spectroscopy; peripheral
      depletion of phospholipids, serotonergic 5-HT2A receptors being linked to
      phospholipase A2; positron emission tomography data with serotonergic ligands;
      and the fact that blockade of serotonergic 5-HT2A receptors by atypical
      neuroleptics slows down the course of the disease. Disruption of glutamate
      signalling by serotonergic overdrive leads to neuronal hypometabolism and
      ultimately synaptic atrophy and grey matter loss according to principles of brain
      plasticity. Normal dopamine input to an impaired ACC causes positive symptoms.
      Frontal lobe hibernation causes negative symptoms and cognitive impairment.

PMID- 23557850
TI  - Idiopathic myelofibrosis and pyoderma gangrenosum involving a mutation of Janus
      kinase 2 (JAK2V617F), showing poor prognosis.

PMID- 23557851
TI  - Political and news media factors shaping public awareness of the HPV vaccine.
AB  - BACKGROUND: In 2006, the U.S. Food and Drug Administration licensed a vaccine for
      the human papillomavirus (HPV) that prevents the strains of HPV that cause 70% of
      cervical cancers. Within months, many states introduced legislation requiring the
      vaccine for girls, prompting controversy and heightened political and media
      attention to the issue. Previous research has shown differences in HPV vaccine
      awareness by individual-level characteristics such as race/ethnicity, income, and
      education levels. We examined how individual political orientation and exposure
      to media coverage can also shape awareness of the vaccine. METHODS: Using data
      from a 2009 Internet survey of 1,216 nationally representative adult respondents
      linked to data on state-specific news coverage, we assessed how political
      orientation, media exposure, and state political context predicted HPV vaccine
      awareness. RESULTS: Younger people, women, and those with more education were
      significantly more likely to be aware of the vaccine. Even after controlling for
      these characteristics, we found that exposure to news media was associated with
      higher HPV vaccine awareness. Whereas liberals and conservatives were both more
      aware of the vaccine compared with moderates, the data are suggestive that
      liberals were more sensitive to news coverage. CONCLUSION: These findings suggest
      that individual-level political identities and their interaction with the
      informational environment may be important factors to consider in evaluating the
      determinants of individuals' attitudes and behaviors related to politically
      charged women's health issues.

PMID- 23557852
TI  - Extensive inter- and intraspecific venom variation in closely related parasites
      targeting the same host: the case of Leptopilina parasitoids of Drosophila.
AB  - The arms race between immune suppressive parasites that produce virulence factors
      and hosts that evolve resistance to these factors is suggested to be a key driver
      for the diversification of both partners. However, little is known regarding the
      diversity of virulence factors in closely related parasites or the mechanisms
      underlying the variation of virulence. One of the best-described model to address
      this issue is the interaction between Leptopilina parasitic wasps and their
      Drosophila hosts, in which variation of virulence is well documented. Thanks to a
      combined transcriptomic and proteomic approach, we have identified the main
      secreted proteins in the venom of Leptopilina heterotoma (Gotheron strain, 66
      proteins) and of two well-characterized strains of Leptopilina boulardi, ISm and
      ISy (65 and 49 proteins, respectively). Results revealed significant quantitative
      differences in venom components between the L. boulardi strains, in agreement
      with their different virulence properties. Strikingly, the two related
      Leptopilina species did not share any abundant venom protein. The main identified
      proteins in L. boulardi were RhoGAPs and serpins while an aspartylglucosaminidase
      (AGA) was found abundant in L. heterotoma. The extensive quantitative variation
      observed between these species may be related with their use of different
      virulence strategies and/or to differences in their host range (specialist versus
      generalist). Altogether, our data suggests that parasitoid venom can quickly
      evolve, mainly through rapid changes in regulation of gene expression. It also
      evidences venom evolutionary processes largely described in other venomous
      animals i.e. the convergent recruitment of venom proteins between
      phylogenetically unrelated organisms, and the role of duplications in the
      emergence of multigenic families of virulence factors.

PMID- 23557853
TI  - Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats.
AB  - AIMS: We investigated the effects of ketogenic diet (KD) on levels of tumor
      necrosis factor alpha (TNF-alpha, a classical pro-inflammatory cytokine), BDNF
      (brain-derived neurotrophic factor, commonly associated with synaptic
      plasticity), and S100B, an astrocyte neurotrophic cytokine involved in metabolism
      regulation. MAIN METHODS: Young Wistar rats were fed during 8weeks with control
      diet or two KD, containing different proportions of omega 6 and omega 3
      polyunsaturated fatty acids. Contents of TNF-alpha, BDNF and S100B were measured
      by ELISA in two brain regions (hippocampus and striatum) as well as blood serum
      and cerebrospinal fluid. KEY FINDINGS: Our data suggest that KD was able to
      reduce the levels of BDNF in the striatum (but not in hippocampus) and S100B in
      the cerebrospinal fluid of rats. These alterations were not affected by the
      proportion of polyunsaturated fatty acids offered. No changes in S100B content
      were observed in serum or analyzed brain regions. Basal TNF-alpha content was not
      affected by KD. SIGNIFICANCE: These findings reinforce the importance of this
      diet as an inductor of alterations in the brain, and such changes might
      contribute to the understanding of the effects (and side effects) of KD in brain
      disorders.

PMID- 23557854
TI  - The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K(+) channels in
      rabbit coronary arterial smooth muscle cells.
AB  - AIMS: We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K)
      inhibitor, on voltage-dependent K(+) (Kv) channels. MAIN METHODS:
      Electrophysiological recordings were performed in freshly isolated rabbit
      coronary arterial smooth muscle cells. KEY FINDINGS: The Kv current amplitude was
      inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48MUM.
      Without alteration of the kinetics of activation, LY294002 accelerated the decay
      rate of Kv channel inactivation. The rate constants of association and
      dissociation for LY294002 were 1.83+/-0.01MUM(-1)s(-1) and 2.59+/-0.14s(-1),
      respectively. Application of LY294002 had no significant impact on the steady
      state activation or inactivation curves. In the presence of LY294002, the
      recovery time constant from inactivation was increased, and Kv channel inhibition
      increased under train pulses (1 or 2Hz). This indicates that LY294002-induced Kv
      channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K
      inhibitor, wortmannin (10MUM), did not affect the Kv current, and did not change
      the inhibitory effect of LY294002. SIGNIFICANCE: Based on these results, we
      suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.

PMID- 23557855
TI  - PI3K and Notch signal pathways coordinately regulate the activation and
      proliferation of T lymphocytes in asthma.
AB  - AIMS: In the present study, we determined whether Phosphoinositide 3-kinase
      (PI3K) and Notch signal pathways are involved in the expression of cyclinD1,
      cyclinA and p27kip1 which were key molecules in controlling cell cycling from
      CD4(+) T lymphocyte in animal model of asthma. MAIN METHODS: Ovalbumin (OVA)
      sensitized murine model of asthma was used to investigate the expression of
      cyclin D1, cyclin A, and p27kip1 by splenic CD4(+) T lymphocytes. We further
      observed the effect of specific inhibitor of PI3K(LY294002) and specific
      inhibitor of Notch(DAPT) on the proliferation of such CD4(+) T lymphocytes. KEY
      FINDINGS: We found that the expression of cyclinD1 and cyclinA was upregulated at
      both protein and mRNA levels in asthma group while p27kip1 was down-regulated.
      Both LY294002 and DAPT inhibit the proliferation of CD4(+) T lymphocytes in a
      time- and dose-dependent manner. Furthermore, LY294002 and DAPT have additive
      effect in down-regulation of cyclinD1 and upregulation of p27kip1. An
      upregulation of cyclinA, although not statistically significant, was also
      observed. SIGNIFICANCE: These data suggested that PI3K signal pathway and Notch
      signal pathway may coordinately regulate the cell proliferation and
      differentiation processes through up-regulating cyclinD1 and down-regulating
      p27kip1 of CD4(+) T lymphocytes.

PMID- 23557856
TI  - Electromagnetic hypersensitive Finns: Symptoms, perceived sources and treatments,
      a questionnaire study.
AB  - The aim was to analyze the subjective experiences of Finns who describe
      themselves as suffering from electromagnetic hypersensitivity (EHS), their
      symptoms, self-perceived sources of the health complaints and the effectiveness
      of medical and complementary alternative therapies. A total of 395 questionnaires
      were mailed to self-diagnosed EHS persons. Of the participants 345 belonged to a
      Finnish self-help group and 50 came from outside of the group. The return rate of
      the study was 52.1% (206) and 80.9% of the respondents were women. Before the
      onset of EHS the most common health complaints were different types of allergies
      (35.1%, 68). During the acute phase of EHS the most common symptoms were nervous
      system related: "stress" (60.3%, 117), "sleeping disorders" (59.3%, 115) and
      "fatigue" (57.2%, 111). The sources that were most often reported to have
      triggered EHS were: "personal computers" (50.8%, 94) and "mobile phones" (47.0%,
      87). The same devices were also claimed to cause the most symptoms during the
      acute phase. After the acute phase of EHS had passed, the respondents still
      claimed to react to these same digital and wireless devices while their reactions
      to basic electrical appliances were reduced. According to 76% of 157 respondents
      the reduction or avoidance of electromagnetic fields (EMF) helped in their full
      or partial recovery. The best treatments for EHS were given as: "dietary change"
      (69.4%), "nutritional supplements" (67.8%) and "increased physical exercise"
      (61.6%). The official treatment recommendations of psychotherapy (2.6%) and
      medication (-4.2%) were not significantly helpful. According to the present
      results the official treatment protocols should take better account the EHS
      person's own experiences. The avoidance of electromagnetic radiation and fields
      effectively removed or lessened the symptoms in EHS persons.

PMID- 23557857
TI  - HFEA reprieved--for the moment!

PMID- 23557858
TI  - Preferential therapy for osteoarthritis by cord blood MSCs through regulation of
      chondrogenic cytokines.
AB  - Osteoarthritis (OA) is a common rheumatic disease associated with imbalanced
      cartilage homeostasis which could be corrected by mesenchymal stem cells (MSCs)
      therapy. However, MSCs from different origins might exhibit distinct
      differentiation capacities. This study was undertaken to compare the therapeutic
      efficacies between MSCs from cord blood (CB-MSCs) and bone marrow (BM-MSCs) on OA
      treatment. The surface phenotypes and multipotent capacities of CB-MSCs and BM
      MSCs were first characterized. The coculture commitment system was subsequently
      utilized for comparing the patterned molecules in stage-specific chondrogenesis
      of committed MSCs. For examining the therapeutic efficacies, committed CB-MSCs
      and BM-MSCs were encapsulated in neo-cartilage and subjected into pro
      inflammatory cytokine environment. Finally, chondrogenic and inflammatory
      cytokine profiles in committed MSCs were evaluated. CB-MSCs and BM-MSCs were both
      negative for hematopoietic markers and positive for adhesion and mesenchymal cell
      markers. The CB-MSCs showed a markedly higher chondrogenic potential and
      relatively lower osteogenic and adipogenic capacities than BM-MSCs. During
      chondrogenesis, the committed CB-MSCs also showed significant increases in cell
      proliferation, adhesion molecules, signaling molecules, and chondrogenic-specific
      gene expressions in a coculture system. For the therapeutic efficacies, the
      committed CB-MSCs could strongly recover the pro-inflammatory cytokines
      diminished-Col II and proteoglycan expressions in a 3D arthritic model. The IL
      10, ICAM-1 and TGF-beta1 were also up-regulated in committed CB-MSCs analyzed by
      using cytokine profiling. Our data demonstrate that CB-MSCs possess specific
      advantages in cartilage regeneration over BM-MSCs. The CB-MSCs showed a better
      therapeutic potential that can contribute to advanced cell-based transplantation
      for clinical OA therapy.

PMID- 23557859
TI  - Graphene oxide modified PLA microcapsules containing gold nanoparticles for
      ultrasonic/CT bimodal imaging guided photothermal tumor therapy.
AB  - Theranostic microcapsules were successfully fabricated by introducing gold
      nanoparticles into poly(lactic acid) microcapsules through a double-microemulsion
      method, followed by depositing graphene oxide onto the microcapsule surface via
      electrostatic layer-by-layer self-assembly technique. It was proved that the
      obtained microcapsules could serve as a contrast agent to simultaneously enhance
      US imaging and X-ray CT imaging greatly both in vitro and in vivo. In addition,
      the in vivo therapeutic examinations showed that the microcapsule was an
      effective agent for photothermal therapy of cancer. The near-infrared laser light
      ablated the tumor completely within 9 days in the presence of the microcapsules
      and the tumor growth inhibition was 83.8%. The combination of real-time
      ultrasound with 3-D computed tomography through a single microcapsule agent is
      very helpful for accurately interpreting the obtained images, identifying the
      size and location of the tumor, as well as guiding and monitoring the
      photothermal therapy. Simultaneously, the effectiveness of photothermal therapy
      could be evaluated by the combined US and CT imaging enhanced by the microcapsule
      agent. Such a versatile microcapsule system might bring opportunities to the next
      generation of multimodal imaging guided cancer therapy.

PMID- 23557860
TI  - Graphene-based magnetic plasmonic nanocomposite for dual bioimaging and
      photothermal therapy.
AB  - In recent years, graphene and graphene-based nanocomposites owning to their
      highly enriched physical and chemical properties have been widely explored for
      applications in many different fields including biomedicine. In the present work,
      we decorate graphene oxide (GO) by both iron oxide nanoparticles (IONPs) and
      gold, forming a multi-functional magnetic & plasmonic GO-IONP-Au nanocomposite
      with strong superparamagnetism and significantly enhanced optical absorbance in
      the near-infrared (NIR) region. We then coat the nanocomposite with polyethylene
      glycol (PEG), obtaining GO-IONP-Au-PEG with high stability in physiological
      environments and no significant in vitro toxicity. Remarkably enhanced
      photothermal cancer ablation effect using GO-IONP-Au-PEG is realized in
      comparison to PEGylated GO used in our earlier studies, as demonstrated in both
      in vitro cell tests and in vivo animal experiments. Moreover, the IONP and Au
      compartments in the GO-IONP-Au-PEG nanocomposite could be further taken
      advantages for magnetic resonance (MR) and X-ray dual-modal imaging. Our work
      shows the promise of using graphene-based multi-functional nanocomposite as
      cancer theranostics.

PMID- 23557861
TI  - The efficacy of nuclease-resistant Chol-siRNA in primary breast tumors following
      complexation with PLL-PEG(5K).
AB  - Modifying the sense strand of nuclease-resistant siRNA with 3'-cholesterol (Chol
      *siRNA) increases mRNA suppression after i.v. administration but with relatively
      low efficacy. We previously found evidence in vitro that suggests complexation of
      Chol-siRNA with PLL-PEG(5K), a block copolymer of poly-l-lysine and 5 kDa
      polyethylene glycol, may increase the efficacy of Chol-siRNA in vivo in a PLL
      block length-dependent manner. In this study, the extent that polyplexes of PLL10
      PEG(5K), PLL30-PEG(5K), and PLL50-PEG(5K) protect complexed Chol-siRNA in high
      concentrations of murine serum and affect the activity of Chol-*siRNA in murine
      4T1 breast tumor epithelial cells in vitro and in primary orthotopic tumors of
      4T1 was compared. PLL-PEG(5K) required 3'-Chol to protect full-length siRNA from
      nuclease degradation in 90% (v/v) murine serum and protection was increased by
      increasing PLL block length and nuclease resistance of Chol-siRNA. Polyplexes of
      Chol-*siLuc suppressed stably expressed luciferase in 4T1-Luc cells to different
      levels in vitro where PLL30 > PLL50 > PLL10. In contrast, only polyplexes of Chol
      *siLuc and PLL30-PEG(5K) or PLL50-PEG(5K) suppressed high levels of luciferase in
      primary orthotopic tumors of 4T1-Luc after i.v. administration, whereas
      polyplexes of Chol-*siLuc and PLL10-PEG(5K), inactive Chol-*siCtrl polyplexes of
      PLL-PEG(5K), or Chol-*siLuc alone had no detectable activity. As a whole, these
      results indicate that polyplexes of PLL-PEG(5K) increase the efficacy of nuclease
      resistant Chol-siRNA in primary breast tumors after i.v. administration in a PLL
      block length-dependent manner. Thus, complexation of Chol-siRNA with PLL-PEG(5K)
      may be a promising approach to increase the efficacy of Chol-siRNA in a wide
      range of primary tumors, metastases, and other tissues but likely requires a PLL
      block length that balances polymer-related adverse effects, Chol-siRNA
      bioavailability, and subsequent activity in the target cell.

PMID- 23557862
TI  - Detection of cadherin-17 in human colon cancer LIM1215 cell secretome and tumour
      xenograft-derived interstitial fluid and plasma.
AB  - Colorectal cancer (CRC), one of the most prevalent cancers in the western world,
      is treatable if detected early. However, 70% of CRC is detected at an advanced
      stage. This is largely due to the inadequacy of current faecal occult blood
      screening testing and costs involved in conducting population-based colonoscopy,
      the 'gold standard' for CRC detection. Another biomarker for CRC,
      carcinoembryonic antigen, while useful for monitoring CRC recurrence, is
      ineffective, lacking the specificity required early detection of CRC. For these
      reasons there is a need for more effective blood-based markers for early CRC
      detection. In this study we targeted glycoproteins secreted from the human colon
      carcinoma cell line LIM1215 as a source of potential CRC biomarkers. Secreted
      candidate glycoproteins were confirmed by MS and validated by Western blot
      analysis of tissue/tumour interstitial fluid (Tif) from LIM1215 xenograft tumours
      grown in immunocompromised mice. Overall, 39 glycoproteins were identified in
      LIM1215 culture media (CCM) and 5 glycoproteins in LIM1215 tumour xenograft Tif;
      of these, cadherin-17 (CDH17), galectin-3 binding protein (LGALS3BP), and
      tyrosine-protein kinase-like 7 (PTK7) were identified in both CM and
      glycosylation motifs. Swiss-Prot was used to annotate Tif. Many of the
      glycoproteins identified in this study (e.g., AREG, DSG2, EFNA1, EFNA3, EFNA4,
      EPHB4, ST14, and TIMP1) have been reported to be implicated in CRC biology.
      Interestingly, the cadherin-17 ectodomain, but not full length cadherin-17, was
      identified in CM, Tif and plasma derived from mice bearing the LIM1215 xenograft
      tumour. To our knowledge, this is the first report of the cadherin-17 ectodomain
      in plasma. In this study, we report for the first time that the presence of full
      length cadherin-17 in exosomes released into the CM. This article is part of a
      Special Issue entitled: An Updated Secretome. 

PMID- 23557863
TI  - Plant secretome - from cellular process to biological activity.
AB  - Recent studies suggest that plants secrete a large number of proteins and
      peptides into the extracellular space. Secreted proteins play a crucial role in
      stress response, communication and development of organisms. Here we review the
      current knowledge of the secretome of more than ten plant species, studied in
      natural conditions or during (a)biotic stress. This review not only deals with
      the classical secretory route via endoplasmic reticulum and Golgi followed by
      proteins containing a known N-terminal signal peptide, but also covers new
      findings about unconventional secretion of leaderless proteins. We describe
      alternative secretion pathways and the involved compartments like the recently
      discovered EXPO. The well characterized secreted peptides that function as
      ligands of receptor proteins exemplify the biological significance and activity
      of the secretome. This article is part of a Special Issue entitled: An Updated
      Secretome. 

PMID- 23557864
TI  - Assessing oral brushing technique as a source to collect DNA and its use in
      detecting human papillomavirus.
AB  - Collecting buccal cell DNA has a number of advantages in terms of practicality
      and technical quality when employed for detecting human papillomavirus (HPV),
      arguably an important etiological factor for head and neck carcinomas. The
      objective of the present study was to assess oropharyngeal mucosa brushing as an
      effective method for collecting DNA samples and for detecting HPV. Forty-three
      female patients diagnosed with cervical intraepithelial neoplasia, and 21 of
      their spouses, both groups without clinically detectable oral lesions, were
      submitted to quantitative and qualitative DNA analysis obtained through buccal
      cell brushing, with spectrophotometry assessment and beta-globin PCR. DNA samples
      were also checked for the presence of HPV. Efficient collection of DNA was
      achieved in all the sample cases. Two samples, a male and a female (not sexual
      partners), showed HPV-positivity. The results revealed that the oral brushing
      technique is an effective method for DNA collection to detect HPV, confirming
      that it could usefully contribute to epidemiological studies undertaken in
      Brazil's Public Health System. HPV detection using PCR showed that only 3.12% of
      the cases were HPV-positive. Although the sample was small, our study
      nevertheless allowed the detection of HPV in DNA samples of oral biological
      material.

PMID- 23557865
TI  - Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative
      fentanyl consumption in Korean gynecologic patients.
AB  - OBJECTIVE: Fentanyl, a MU-opioid receptor agonist, is a substrate of P
      glycoprotein. Its metabolism is catalyzed by CYP3A4 and CYP3A5. The aim of this
      study was to investigate the association between postoperative fentanyl
      consumption and genetic polymorphisms of MU-opioid receptor (OPRM1), ABCB1 (gene
      encoding P-glycoprotein), CYP3A4 and CYP3A5 in Korean patients. METHODS: 196
      female patients scheduled to undergo total abdominal hysterectomy or laparoscopic
      assisted vaginal hysterectomy under general anesthesia were enrolled in this
      study. Intravenous patient-controlled analgesia with fentanyl was provided
      postoperatively. Cumulative fentanyl consumption was measured during the first 48
      hours postoperatively. The severity of pain at rest was assessed with the visual
      analogue scale. OPRM1 118A>G, ABCB1 2677G>A/T, ABCB1 3435C>T, CYP3A4*18 and
      CYP3A5*3 variant alleles were genotyped. The effects of genetic and non-genetic
      factors on fentanyl requirements were evaluated with multiple linear regression
      analysis. RESULTS: The 24-hour cumulative fentanyl doses were significantly
      associated with pain core, weight and type of surgery (p < 0.05). The 48-hour
      cumulative fentanyl doses were significantly associated with pain score, type of
      surgery and history of PONV or motion sickness (p < 0.05). Genetic polymorphisms
      were not associated with fentanyl requirements. CONCLUSION: In Korean gynecologic
      patients, no association was found between genetic factors and postoperative
      fentanyl consumption.

PMID- 23557866
TI  - Lack of a relationship between the serum concentration of aminoglycosides and
      ototoxicity in neonates.
AB  - INTRODUCTION: Gentamicin and the other aminoglycosides are toxic antibiotics, but
      they are urgently needed to treat newborns with neonatal sepsis. Aminoglycosides
      are well known for their nephrotoxicity and ototoxicity. The aminoglycoside
      dosage currently applied in Indonesia is derived from studies done in Caucasian
      populations. The safety and efficacy of this dosage regimen, however, has never
      been evaluated to date. The pharmacokinetic profile of drugs may vary between
      populations and this may be influenced by genetic factors, lifestyle, drug
      interactions, etc. The detection of aminoglycoside toxicity in newborns is
      usually problematic. The present study aims to know the proportion of ototoxicity
      in newborns in the Cipto Mangunkusumo Hospital treated with gentamicin or
      amikacin in relation to their trough serum concentration. METHODS: The serum
      level of gentamicin and amikacin were quantified using Liquid Chromatography
      Tandem Mass Spectrometry (LC-MSMS), and is assumed to be safe if the trough serum
      concentrations are < 2 mcg/ml and effective if it is between 5 - 12 mcg/ml. For
      amikacin the desired trough serum concentrations are < 10 mcg/ml and the peak is
      between 20 - 30 mcg/ml. The hearing function was assessed by Distortion Product
      Otoacoustic Emission (DPOAE) instrument. This study is registered with the
      www.clinicaltrials.gov NCT01624324. CONCLUSION: Our study indicated that there
      was no relationship between aminoglycosides serum trough concentration and
      ototoxicity in neonates with neonatal sepsis.

PMID- 23557867
TI  - CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in
      Chinese renal transplant recipients.
AB  - OBJECTIVE: Both cyclosporine and tacrolimus display a narrow therapeutic index as
      well as high interindividual pharmacokinetic variability. We approached the
      effect of the CYP3A4*18B and CYP3A5*3 polymorphisms and haplotypes on the whole
      blood cyclosporine or tacrolimus concentration in Chinese renal transplant
      patients during the first month after transplantation. MATERIALS AND METHODS: A
      total of 83 recipients receiving tacrolimus or cyclosporine was genotyped by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      The whole blood concentration was measured by enzyme-multiplied immunoassay
      technique. RESULTS: Both CYP3A4*18B and CYP3A5*3 polymorphisms affected the
      tacrolimus dose-adjusted trough concentration (C0/D). The tacrolimus C0/D was
      higher in carriers of haplotype GG compared with the non-carriers. The
      cyclosporine dose-adjusted 2-hour post-dose concentrations (C2/D), dose-adjusted
      C0 + C2 ((C0 + C2)/D) and C2/C0 during Days 15 - 21 displayed significant
      difference among the three genotypes. Statistical difference was observed between
      CYP3A4*1/*1 and CYP3A4*18B/*18B groups and between CYP3A4*1/*18B and
      CYP3A4*18B/*18B groups, but no difference was detected between CYP3A4*1/*1 and
      CYP3A4*1/*18B groups. No difference was found in C0/D among the three genotypes
      of CYP3A4*18B polymorphism, and neither CYP3A5*3 polymorphisms nor CYP3A
      haplotype-derived genotypes affected the cyclosporine dose-adjusted
      concentration. CONCLUSIONS: Genetic polymorphisms of CYP3A5*3 and CYP3A4*18B may
      be partly responsible in large interindividual variability of cyclosporine and
      tacrolimus blood levels in Chinese renal transplant patients during the first
      month after transplantation. A patient carried combined genotype of CYP3A4*1/*1
      CYP3A5* 3/*3 might require lower tacrolimus doses to achieve target concentration
      levels. Genotyping of CYP3A4*18B and CYP3A5*3 before transplantation is of
      benefit in determining a suitable initial dose for each patient.

PMID- 23557868
TI  - Lenalidomide-induced acute lung injury in case of multiple myeloma.
AB  - OBJECTIVE: Lenalidomide is now widely used for the treatment of multiple myeloma
      in virtue of its potent anti-tumor activity and low toxicity. Very few reports
      stressed the association of this drug with serious pulmonary toxicity. Here we
      present the case of multiple myeloma who underwent acute respiratory failure
      caused by non-specific interstitial pneumonia after few days of treatment with
      lenalidomide. CASE SUMMARY: A 50-year-old man diagnosed as multiple myeloma of
      IgA kappa type, International Staging System III received a combination therapy
      of lenalidomide (15 mg, Day 1 - 21) with dexamethasone (40 mg, Day 1, 8, 15, 22).
      After 4 days on chemotherapy, he experienced worsened dyspnea and was urgently
      hospitalized because of acute respiratory failure. Because serial imaging
      procedures and thorough laboratory workup strongly suggested that his lung injury
      was caused by drug-induced interstitial pneumonia, lenalidomide, which was the
      most suspicious drug, was discontinued immediately, and the glucocorticoid pulse
      was performed. He showed an excellent response to the therapy. Interstitial
      pneumonia on the CT scan was resolved dramatically at 12 days after the start of
      the glucocorticoid pulse. CONCLUSION: We are convinced that our case is so
      instructive as to arouse attention to clinicians that lenalidomide has an
      extremely rare but potential adverse effect.

PMID- 23557869
TI  - Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in
      patients with alcoholic liver disease.
AB  - BACKGROUND & AIMS: Vitamin D deficiency has been frequently reported in advanced
      liver disease. However, its influence on alcoholic liver disease (ALD) has been
      poorly elucidated. We investigated the association of vitamin D with clinical,
      biological, and histological parameters and survival in ALD patients.
      Furthermore, we explored the effect of vitamin D treatment on ALD patient
      peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of
      ALD. METHODS: Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in
      324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on
      vitamin D pre-treated PBMCs evaluated TNFalpha production by ELISA in culture
      supernatants. Mice were submitted to an ethanol-fed diet and some of them were
      orally supplemented three times per week with 1,25(OH)2D. RESULTS: Severe
      deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher
      aspartate aminotransferase levels (p=1.00 * 10(-3)), increased hepatic venous
      pressure gradient (p=5.80 * 10(-6)), MELD (p=2.50 * 10(-4)), and Child-Pugh
      scores (p=8.50 * 10(-7)). Furthermore, in multivariable analysis, a low 25(OH)D
      concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18-3.84, p=0.013)
      and mortality (HR=4.33, 95% CI=1.47-12.78, p=7.94 * 10(-3)) at one year. In
      addition, in vitro, 1,25(OH)2D pretreatment decreased TNFalpha production by
      stimulated PBMCs of ALD patients (p=3.00 * 10(-3)), while in vivo, it decreased
      hepatic TNFalpha expression in ethanol-fed mice (p=0.04). CONCLUSIONS: Low
      25(OH)D levels are associated with increased liver damage and mortality in ALD.
      Our results suggest that vitamin D might be both a biomarker of severity and a
      potential therapeutic target in ALD.

PMID- 23557870
TI  - Pulmonary contraindications, indications and MELD exceptions for liver
      transplantation: a contemporary view and look forward.
AB  - Pulmonary concerns in liver transplant candidates have intraoperative and outcome
      implications. Evolving MELD exception policies address transplant priority for
      problems such as hepatopulmonary syndrome, portopulmonary hypertension, and
      hemorrhagic hereditary telangiectasia. Other pulmonary issues such as refractory
      hepatic hydrothorax, advanced chronic obstructive lung disease (including alpha-1
      antitrypsin deficiency) and indeterminate pulmonary nodules may affect liver
      transplant consideration. Herein, we discuss current pulmonary-related
      contraindications, indications and MELD exception policies for liver
      transplantation, suggesting future considerations. 

PMID- 23557871
TI  - Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases.
AB  - Exosomes are small (30-100 nm in diameter) extracellular membrane-enclosed
      vesicles released by different cell types into the extracellular space or into
      biological fluids by exocytosis as a result of fusion of intracellular
      multivesicular bodies with the plasma membrane. The primary function of exosomes
      is intercellular communication with both beneficial (physiological) and harmful
      (pathological) potential outcomes. Liver cells are exosome-releasing cells as
      well as targets for endogenous exosomes and exosomes derived from cells of other
      organs. Despite limited studies on liver exosomes, initial observations suggest
      that these vesicles are important in liver physiology and pathophysiology. In
      this review, we briefly summarize the recent findings on liver exosomes, their
      functions and significance for novel diagnostic and therapeutic approaches.

PMID- 23557872
TI  - Site-specific organ-selective effect of epifascial acupuncture on cardiac and
      gastric autonomic functions.
AB  - Needle stimulation at the specific sites of body surface modulates autonomic
      functions in various organs. To examine their site-specificity and organ
      selectivity, the changes in electrogastrogram (EGG) and heart rate variability
      (HRV) with such stimulation at PC6 (forearm), BL20 (back), CV12 (abdomen), BL32
      (sacral), and ST36 (lower leg) were analyzed in healthy men. Stimulation at CV12
      increased vagal HRV component without affecting dominant EGG frequency.
      Conversely, stimulation at BL32 decreased dominant EGG frequency without
      affecting vagal HRV component. Stimulation at the other points affected neither
      of them. These support site-specific and organ-selective effect of body surface
      needle stimulation on autonomic functions. 

PMID- 23557873
TI  - CD3+CD56+natural killer T cells in fibromyalgia syndrome patients: association
      with the intensity of depression.
AB  - OBJECTIVES: Fibromyalgia syndrome (FMS) patients have multiple symptoms,
      including mental symptoms such as depression. Natural killer T (NKT) cells have
      shown to be correlated with depression. However, up to now there is no
      information regarding the role of CD3+CD56+NKT cells in FMS patients, especially
      in the intensity of mental symptoms. The present study aimed to observe the role
      of CD3+CD56+NKT cells level in FMS patients in relation to the intensity of
      depression. METHODS: Ninety-six female patients who matched definition of FMS
      were divided into subgroups of depressions according to Hospital Anxiety and
      Depression Scale (HADS) score (HADS-Depression <8; 8-10; and >10). CD3+CD56+NKT
      cells from peripheral blood were measured by fluorescence-activated cell sorting
      methods. RESULTS: ANOVA test in the subgroup of depression of FMS patient showed
      significant differences. Additionally, the differences were observed in HADSD <8
      and >10. The use of antidepressant significantly altered the level of
      CD3+CD56+NKT cells. A blocking variable ANCOVA with antidepressant as covariate
      showed main effects in the subgroup of depression, however, the interaction of
      antidepressant and the subgroup of depression did not influence the level of
      CD3+CD56+NKT cells. CONCLUSIONS: These results suggest that CD3+CD56+NKT cells
      could play a role as a mediator in mental symptom such as depression in FMS
      patients. It seems the role of antidepressant in the mood intensity is not
      mediated by CD3+CD56+NKT cells in FMS patients. Additionally, subgrouping FMS
      patients based on the intensity of mental symptoms may help to optimise the
      treatments.

PMID- 23557874
TI  - IgG4-related skin manifestations in patients with IgG4-related disease.
AB  - We describe two cases of IgG4-related disease associated with skin manifestations
      with IgG4-positive plasma cells. The first patient was a 52-year-old woman with a
      3-year history of IgG4-related sialadenitis who presented with pruritic,
      indurated erythematous lesions on the auricle, postauricular and submandibular
      regions and neck. A skin biopsy showed infiltration of IgG4-positive plasma cells
      in the subcutaneous tissue. The second patient was a 53-year-old woman with IgG4
      related lesions in the ocular adnexal tissues and nasal cavity who presented with
      pruritic, indurated erythema on the cheek and submandibular region.
      Histopathological examination of a skin biopsy revealed a dense, patchy
      infiltrate comprised of lymphocytes, IgG4-positive plasma cells and eosinophils
      around blood vessels and sweat glands in the entire dermis and subcutis. The skin
      lesions in these cases were considered to be skin manifestations of IgG4-related
      disease. The findings of these two cases together with the three reported cases
      of IgG4-related disease with skin manifestations in the literature suggest that
      IgG4-related skin lesions may appear on the scalp, face, neck, auricle and
      postauricular regions during the course of IgG4-related disease.

PMID- 23557875
TI  - Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease
      progression.
AB  - 24S-hydroxycholesterol (24OHC) is involved in the conversion of excess
      cholesterol in the brain, and its level in plasma is related to the number of
      metabolically active neuronal cells. Previous research suggests that plasma 24OHC
      is substantially reduced in the presence of neurodegenerative disease. Huntington
      disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused
      by a cytosine-adenine-guanine (CAG) triplet repeat expansion in the coding region
      of the huntingtin (HTT) gene. The current study focused on the relative
      importance of 24OHC as a marker of HD progression. Using mass spectrometry
      methods, we examined plasma 24OHC levels in three groups of gene-expanded
      individuals (Low, Medium, High) characterized by their progression at entry into
      the parent PREDICT-HD study, along with a group of non-gene-expanded controls
      (total N=150). In addition, the correlation of 24OHC with a number of motor,
      cognitive, and imagining markers was examined, and effect sizes for group
      differences among the markers were computed for comparison with 24OHC. Results
      show a progression gradient as 24OHC levels decreased as the progression group
      increased (Low to High). The effect size of group differences for 24OHC was
      larger than all the other variables, except striatal volume. 24OHC was
      significantly correlated with many of the other key variables. The results are
      interpreted in terms of cholesterol synthesis and neuronal degeneration. This
      study provides evidence that 24OHC is a relatively important marker of HD
      progression.

PMID- 23557876
TI  - Response to Mrs. Rapley's comments.

PMID- 23557877
TI  - Response to the paper by Caroli et al.

PMID- 23557878
TI  - The worrisome liaison between left ventricular systolic dysfunction and mitral
      annulus calcification in type 2 diabetes without coronary artery disease: data
      from the SHORTWAVE study.
AB  - BACKGROUND AND AIM: Mitral annulus calcification (MAC) is a marker for coronary
      artery disease (CAD) and predicts poor outcome in the general population. No data
      are available on MAC in patients with type 2 diabetes. In these patients we
      assessed prevalence of MAC and the relation between MAC and left ventricular (LV)
      systolic function. METHODS AND RESULTS: As many as 386 patients with type 2
      diabetes without CAD were studied with Doppler echocardiography. LV systolic
      dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected
      midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S')
      were considered as indexes of LV circumferential and longitudinal shortening and
      classified low if <89% and <8.5 cm/s, respectively (10th percentiles of
      controls). Patients who had MAC (107 = 28%) were older with longer duration of DM
      and were receiving more anti-hypertension medications than those who had not. At
      echocardiographic evaluation patients with MAC showed higher LV mass, larger left
      atrial volume (LAV), reduced sc-MS (88.4 +/- 14.9 vs 92.6 +/- 14.3%; p = 0.01)
      and peak S' (8.9 +/- 2.2 vs 10.0 +/- 2.0 cm/s; p < 0.001) than patients without
      MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06],
      p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction
      in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors
      associated with MAC. CONCLUSIONS: MAC is detectable in one fourth of patients
      with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction
      expressed as combined impairment of LV circumferential and longitudinal fibers,
      independent of age and LAV.

PMID- 23557880
TI  - Adhesive interaction of functionalized particles and endothelium in idealized
      microvascular networks.
AB  - OBJECTIVE: Leukocytes play a key role in the early response to tissue
      injury/infection resulting from physical, chemical or biological stimuli. This
      process involves the initiation of the leukocyte adhesion cascade mediated by a
      series of interactions between receptors and ligands on the endothelium and the
      leukocytes. Here, we characterize the adhesion profile of functionalized
      particles under physiological flow conditions in an idealized synthetic
      microvascular network (SMN) characterized by a bifurcation. We hypothesize that
      differences in the level of adhesion of functionalized particles in bifurcating
      SMNs are dependent on the ratio of adhesion molecules on the particles as well as
      geometric features of the in vitro networks. METHODS: Functionalized particles
      were prepared by coating their surfaces with different ratios of antibodies
      against ICAM-1 and E-selectin (aICAM-1:aE-selectin=100:0, 70:30, 50:50, 30:70,
      and 0:100). The adhesion of functionalized particles to 4h TNF-alpha activated
      human umbilical vein endothelial cells under shear flow (0.5, 2, and 4dyn/cm(2))
      in bifurcating SMNs and in a parallel plate flow chamber was then quantified.
      RESULTS: The level of adhesion of 50:50 aICAM-1:aE-selectin particles was
      significantly higher compared to other particles in the bifurcating SMNs (~1.5-4
      fold higher). However, in the parallel plate flow chamber 70:30 aICAM-1:aE
      selectin particles exhibited a significantly higher level of adhesion (~1.5-2.5
      fold higher). Furthermore, the adhesion of particles in junction regions was
      about 3-18 fold higher than that in straight sections of the SMNs. As expected,
      in straight sections of the SMNs and in the parallel plate flow chamber particle
      adhesion increased with decreasing shear. However, particle adhesion did not
      change significantly with decreasing shear at the junction regions of SMNs for
      all functionalized particles. CONCLUSION: Adhesion efficiency of functionalized
      particles is significantly affected by cell-adhesion molecule ratio density as
      well as geometric features of the vessels. Moreover, the differential adhesion
      patterns of particles between straight sections of bifurcating SMNs and parallel
      plate flow chamber, as well as straight sections and junction regions of
      bifurcating SMNs, indicates that adhesion profile of particles is highly
      dependent on the vascular geometry of the system used.

PMID- 23557879
TI  - The fatty liver index is associated with increased mortality in subjects referred
      to coronary angiography.
AB  - BACKGROUND AND AIMS: Fatty liver index (FLI), a surrogate parameter for
      nonalcoholic fatty liver disease, is an emerging risk factor for cardiovascular
      diseases and mortality. We aimed to evaluate whether FLI is associated with all
      cause, cardiovascular, and non-cardiovascular mortality as well as fatal cancer
      in a cohort of subjects routinely referred to coronary angiography. METHODS AND
      RESULTS: FLI was calculated using BMI (body mass index), waist circumference
      (WC), triglycerides (TG) and gamma-glutamyl transferase (GGT) in 3270 subjects
      who were referred to coronary angiography (1997-2000). The main outcome measures
      were Cox proportional hazard ratios (HRs) for mortality from all causes,
      cardiovascular causes, non-cardiovascular causes, and fatal cancer. After a
      median follow-up time of 7.7 years, 740 subjects (22.6%) had died. There were 437
      deaths due to cardiovascular disease and 303 deaths due to non-cardiovascular
      disease. Age-, sex-, and BMI-adjusted HRs (with 95% confidence intervals) for all
      cause, cardiovascular, and non-cardiovascular mortality in the highest compared
      to the lowest FLI quartile were 2.56 (1.90-3.43; p < 0.001), 2.17 (1.47-3.22; p <
      0.001), and 3.49 (2.16-5.66; p < 0.001), respectively. In age-, sex-, and BMI
      adjusted analyzes, we found no significant association of FLI with fatal cancer.
      Multivariate adjusted HRs for all-cause, cardiovascular, non-cardiovascular
      mortality, and fatal cancer in the highest compared to the lowest FLI quartile
      were 2.17 (1.58-2.99; p < 0.001), 1.64 (1.07-2.51; p = 0.023), 3.72 (2.22-6.24; p
      < 0.001), and 2.33 (1.01-5.41; p = 0.048) respectively. CONCLUSION: In subjects
      referred to coronary angiography, high FLI levels are independently associated
      with increased all-cause, cardiovascular, and non-cardiovascular mortality as
      well as fatal cancer.

PMID- 23557882
TI  - Implications from platelet-leukocyte aggregates in inflammatory bowel disease:
      current and future status.

PMID- 23557881
TI  - Specific aspects of cognitive and language proficiency account for variability in
      neural indices of semantic and syntactic processing in children.
AB  - The neural activity mediating language processing in young children is
      characterized by large individual variability that is likely related in part to
      individual strengths and weakness across various cognitive abilities. The current
      study addresses the following question: How does proficiency in specific
      cognitive and language functions impact neural indices mediating language
      processing in children? Thirty typically developing seven- and eight-year-olds
      were divided into high-normal and low-normal proficiency groups based on
      performance on nonverbal IQ, auditory word recall, and grammatical morphology
      tests. Event-related brain potentials (ERPs) were elicited by semantic anomalies
      and phrase structure violations in naturally spoken sentences. The proficiency
      for each of the specific cognitive and language tasks uniquely contributed to
      specific aspects (e.g., timing and/or resource allocation) of neural indices
      underlying semantic (N400) and syntactic (P600) processing. These results suggest
      that distinct aptitudes within broader domains of cognition and language, even
      within the normal range, influence the neural signatures of semantic and
      syntactic processing. Furthermore, the current findings have important
      implications for the design and interpretation of developmental studies of ERPs
      indexing language processing, and they highlight the need to take into account
      cognitive abilities both within and outside the classic language domain.

PMID- 23557883
TI  - Rotational atherectomy in the era of drug-eluting stents.

PMID- 23557884
TI  - Circulating platelet-leukocyte aggregates in patients with inflammatory bowel
      disease.
AB  - BACKGROUND: Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative
      colitis are considered to be chronic inflammatory disorders implicated with
      recurrent tissue damage to the intestine. There is a positive correlation between
      platelet-leukocyte aggregates and ischemic vascular risk. There are limited data
      about the relationship between platelet-leukocyte aggregates and IBD. This study
      was designed to determine whether platelet-leukocyte aggregates increase in IBD,
      and whether a relationship exists between the elevation of platelet-leukocyte
      aggregates and disease activity. METHODS: A total of 20 patients with IBD (16
      with ulcerative colitis and 4 with Crohn's disease) and 20 healthy controls
      participated in our study. Nine patients were in active-phase IBD, whereas 11
      patients were in inactive phase. To show the presence of thrombocyte aggregates,
      the monoclonal antibodies such as Isotype IgG1 mouse antihuman CD42b-PE
      (phycoerythrin) (Beckman Coulter IMI417), Isotype IgG1 mouse antihuman CD45-FITC
      (fluorescein isothiocyanate) (Beckman Coulter IM0782), and Isotype IgG2a mouse
      antihuman CD45RO-FITC (Beckman Coulter IMI247) were used. Additionally, the
      values of platelet-neutrophil aggregates were measured in peripheral blood
      samples using flow cytometry techniques. RESULTS: The levels of platelet
      leukocyte aggregates in blood samples were found to be significantly higher
      during both the active and inactive phases in patients with IBD. There were no
      statistically significant differences between active-phase and inactive-phase
      patients. CONCLUSION: We determined that the patient group had significantly
      higher platelet-leukocyte aggregate levels compared with the control group. This
      finding suggests that platelet-leukocyte aggregates may play a role in the
      development of IBD.

PMID- 23557885
TI  - Validation of the behavior and concept based assessment of professionalism
      competence in postgraduate first-year residents.
AB  - BACKGROUND: The evaluation of professional behaviors and concepts of postgraduate
      first-year (PGY1) residents has been identified as an area for development. This
      study examined the efficiency of the professionalism-assessing objective
      structured clinical examination (OSCE), 360 degrees  evaluation, and mini
      Clinical Examination Exercise scores (mini-CEX; p-OSCE, p-360 degrees 
      evaluation, and p-mini-CEX scores). METHODS: Between January 2009 and January
      2012, 189 PGY1 residents were evaluated for behavior- and concept-based
      professionalism competence based on the above three methods using two checklists
      unique to each case. Data were analyzed for reliability, inter-rater agreement,
      interval changes, and gender-related difference for each method. RESULTS: The
      test reliabilities of p-OSCE, p-360 degrees  evaluation, and p-mini-CEX were
      acceptable. Further, the reliability of concept and combined p-OSCE was higher
      than that of behavior p-OSCE. In addition, the concept OSCE p-scores and behavior
      360 degrees  evaluation p-scores were significantly improved after 6 months of
      training. The inter-rater agreements were relatively good in p-OSCE and p-360
      degrees  evaluation. Interestingly, male PGY1 residents had higher behavior 360
      degrees  evaluation p-scores from nurses than those of females, whereas female
      PGY1 residents had higher behavior 360 degrees  evaluation p-scores from patients
      than those of males. Behavior and concept OSCE p-scores were positively
      correlated with behavior 360 degrees  evaluation p-scores. In comparison with p
      360 degrees  evaluation, the combination of p-360 degrees  evaluation + OSCE +
      mini-CEX significantly increases their reliabilities. CONCLUSION: The current
      study suggests that the p-OSCE, p-360 degrees  evaluation, and p-mini-CEX are
      feasible methods for evaluating professionalism in clinical training of PGY1
      residents. Combination of the above three evaluations, participation, and support
      from multiple constituencies and multiple representatives provides good
      reliability and adds credibility in the assessment of professionalism competence.

PMID- 23557887
TI  - Spatial and temporal analysis of nociception-related spinal cord matrix
      metalloproteinase expression in a murine neuropathic pain model.
AB  - BACKGROUND: Although the mammalian central nervous system contains numerous
      matrix metalloproteinases (MMPs), the significance of each MMP relative to
      nociception remains obscure. Working from the hypothesis that MMPs may be
      involved in activity-dependent reorganization during neuronal modulation, we
      explored the role of each MMP following neuropathological injury by establishing
      MMP expression profiles in a murine model for neuropathic pain. METHODS: Sciatic
      nerves of adult male C57BL/6C mice were partially ligated, and their responses to
      mechanical and radiant heat stimulations were observed at 1, 3, 7, and 14 days.
      The expression of several nociception-related MMPs (MMP-2, MMP-9, MMP-12, MMP-17,
      and MMP-24) in the spinal cord was detected by immunohistochemical analysis,
      Western blotting, and real-time polymerase chain reaction. In addition, the
      potential of GM6001, a general inhibitor of MMP peritoneal administration, to
      modulate nociceptive pain responses in a chronic neuropathic pain model in mice
      was also investigated. RESULTS: MMP-2, 9, 17, and 24, but not MMP-12, were
      expressed in the murine spinal cord. MMP-9 was constitutively expressed in
      neurons and microglial cells, immediately upregulated after nerve injury, and
      returned to baseline levels at day 3. Expression of MMP-2, MMP-17, and MMP-24
      gradually increased after nerve injury. Morphologically, MMP-2-positive cells
      were glial-like cells. MMP-17 and MMP-24 expression was widespread in gray
      matter, neurons, and microglial cells, and concentrated in the marginal zone of
      the dorsal horn and in small capillaries. Peritoneal administration of GM6001
      resulted in significantly attenuated thermal hyperalgesia and tactile allodynia
      induced by nerve injury. CONCLUSION: Expression of several nociception-related
      MMPs was differentially regulated both temporally and spatially following nerve
      injury. These results suggest that neuronal remodeling requires concerted
      expression of particular MMPs in specific temporal and spatial patterns, which
      may be necessary for neuronal plasticity and/or recovery.

PMID- 23557886
TI  - Absolute lymphocyte count predicts response to rituximab-containing salvage
      treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior
      rituximab exposure.
AB  - BACKGROUND: Rituximab-containing salvage chemotherapy has shown promising
      efficacy in patients with relapsed/refractory B-cell non-Hodgkin's lymphoma
      (NHL). The aim of this study was to examine the efficacy of rituximab-containing
      treatment in patients with B-cell NHL who developed relapsed or refractory
      disease after prior rituximab use and to explore the predictive factors of
      response using this approach. METHODS: Patients with relapsed/refractory B-cell
      NHL who received rituximab-containing salvage treatment after failing first-line
      rituximab-combining chemotherapy were enrolled in this retrospective study. The
      characteristics of the patients were collected and analyzed. Logistic regression
      analysis was used for determining predictive factors of response to rituximab
      containing salvage treatment. RESULTS: A total of 68 patients were enrolled in
      this study and the overall response rate to rituximab-containing salvage
      treatment was 61.7%. The median event-free survival and overall survival with
      rituximab-containing salvage treatment was 11.3 and 21.73 months, respectively.
      Results of a multivariate analysis showed high absolute lymphocyte count at the
      time of rituximab-containing salvage treatment [(ALC-R), ALC-R >= 1000/UL, p =
      0.003)], which was the only independent factor predicting response to rituximab
      containing salvage treatment. CONCLUSION: Our study results show that for
      patients with relapsed/refractory B-cell NHL, rituximab-containing salvage
      treatment is feasible and generally tolerable. A high ALC-R value was
      significantly associated with a better response to this treatment.

PMID- 23557888
TI  - Treatment selection for tonsillar squamous cell carcinoma.
AB  - BACKGROUND: The optimal treatment for tonsillar squamous cell carcinoma (SCC)
      remains controversial. The purpose of this study was to evaluate long-term
      treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate
      treatment selection. METHODS: We conducted a retrospective chart review of 105
      patients with curatively treated tonsillar SCC between January 1996 and December
      2005. Forty-three patients (41.0%) underwent primary surgery with or without
      adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated
      with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty
      patients (19%) received tumor tonsillectomy before definitive RT/CRT and were
      grouped into the organ preservation group. RESULTS: No significant differences
      were observed between the primary surgery and organ preservation groups in terms
      of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p
      = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival
      rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term
      dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also
      similar. Advanced T classification (T3-4) was the only factor associated with
      significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also
      no difference in final treatment outcomes in T3-4 patients regardless of whether
      they were treated with primary surgery or RT/CRT. In the organ preservation
      group, tumor tonsillectomy before RT/CRT did not improve local control (p =
      0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p =
      0.745). CONCLUSION: Both primary surgery and RT/CRT organ preservation are
      effective treatments for tonsillar SCC. Single modality treatment, either surgery
      or RT/CRT, can typically be provided for stage I-II diseases. Although RT/CRT
      organ preservation is used more frequently for stage III-IV tonsillar SCC in
      recent years, primary surgery combined with adjuvant therapy still achieves
      equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities
      and personnel available are therefore important for decision-making. In addition,
      if RT/CRT organ preservation is selected as the primary treatment, tumor
      tonsillectomy is not indicated.

PMID- 23557889
TI  - Application of color-coded digital subtraction angiography in treatment of
      indirect carotid-cavernous fistulas: initial experience.
AB  - BACKGROUND: Parametric-colored digital subtraction angiography using Tmax is
      almost a routine angiographic imaging procedure, currently. The current
      feasibility study is aimed to using the imaging to monitor treatment effects
      while embolizing indirect carotid-cavernous fistulas (CCF). METHODS: Ten patients
      with CCFs receiving embolization and 40 patients with normal circulation time
      were recruited. Their color-coded DSAs were used to define the Tmax of selected
      intravascular ROIs. A total of 19 ROIs in the internal carotid artery (ICA)
      (cervical segment of ICA in AP view (I0), cavernous segment of ICA in AP view
      (I1), supraclinoid segment of ICA in AP view (I2) and cervical segment of ICA in
      lateral view (I0'), cavernous portion of ICA in lateral view (IA), supraclinoid
      portion of ICA in lateral view (IB)), ACA (first segment of anterior cerebral
      artery, second segment of anterior cerebral artery (A1, A2)), middle cerebral
      vein (MCA) first segment of MCA ((M1), second segment of MCA (M2)), frontal vein
      (FV), parietal vein (PV), superior sagittal sinus (SSS), sigmoid sinus (SS),
      internal jugular vein (JV), fistula, superior ophthalmic vein (SOV), inferior
      petrosal vein (IPS), and MCV were selected. Relative Tmax was defined as the Tmax
      at selected ROIs minus Tmax at I0 or I0'. An intergroup comparison between the
      normal and treatment groups and pre- and post-treatment comparison of the peri
      therapeutic rTmax for the treatment group were performed. RESULTS: rTmax's for
      the normal group were as follows: Anterior-posterior view: I1: 0.16, I2: 0.32,
      A1: 0.31, M1: 0.35, SSS: 6.16, SS: 6.56, and MCV: 3.86 seconds. Lateral view: IA:
      0.05, IB: 0.20, A2: 0.53, M2: 0.95, FV: 4.84, PV: 5.12, IPS: 4.62, JV: 6.81, and
      MCV: 3.86 seconds. Before embolization, rTmax of the IPS, SS, and JV for the
      treatment group were shortened (p < 0.05). No rTmaxs for any arterial ROIs in the
      fistula group were significantly different. After embolization, the rTmaxs for
      all venous ROIs returned to normal except for two which were partially
      obliterated. CONCLUSION: This postprocessing method does not require extra
      radiation exposure and contrast media. It facilitates real-time hemodyamic
      monitoring and may help determining the endpoint of embolization, which increases
      patient safety.

PMID- 23557890
TI  - Body mass index and active range of motion exercise treatment after intra
      articular injection in adhesive capsulitis.
AB  - BACKGROUND: Adhesive capsulitis is commonly associated with medical diseases such
      as diabetes mellitus, hyperthyroidism, and obesity. Intra-articular injection has
      been used to speed recovery and relieve pain associated with frozen shoulder. In
      this study, we evaluated and compared the effects of an intra-articular injection
      of corticosteroid and lidocaine in the treatment of primary adhesive capsulitis
      in overweight and normal-weight patients. METHODS: This is a prospective clinical
      study of patients with adhesive capsulitis, in which the main treatment strategy
      was an intra-articular injection of corticosteroid (3 mL) and lidocaine (3 mL).
      Active range of motion exercise was initiated immediately after the injection and
      performed four times daily. The evaluation included the recording of a detailed
      medical and orthopedic history, and the assessment of pain and function by
      determining the Constant score at baseline (before injection) and every 2 weeks
      thereafter. Patients were classified as normal weight (body mass index [BMI] < 25
      kg/m(2)) or overweight (BMI >= 25 kg/m(2)). The Constant scores of all patients
      were compared at 8 weeks after injection. RESULTS: After clinical examinations
      and radiographic and ultrasonographic studies, 79 patients were treated for
      adhesive capsulitis between 2010 and 2012. In the normal-weight group, the mean
      Constant score increased from 35.4 to 74.6 after 8 weeks, whereas in the
      overweight group, the mean Constant score increased from 32.0 to 47.2. There was
      a significant difference in the mean Constant score between the normal-weight and
      overweight groups at 8 weeks. CONCLUSION: Active range of motion exercise after
      an intra-articular injection of corticosteroid and lidocaine improved pain and
      functional outcome at 8 weeks in normal-weight (BMI < 25 kg/m(2)) patients with
      primary adhesive capsulitis. Manipulation under anesthesia may be considered a
      priority in overweight patients.

PMID- 23557891
TI  - Klippel-Trenaunay syndrome in combination with congenital dislocation of the hip.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare and sporadic disorder characterized by
      the triad of capillary malformations, venous varicosities, and limb hypertrophy.
      The clinical manifestations of KTS are heterogeneous. In this report, we present
      a unique case of KTS in combination with congenital dislocation of the hip (CDH)
      in a 4-day-old female neonate. The patient had a widespread port-wine stain
      surrounded by regions of unaffected skin in a mosaic pattern, cutaneous
      hemangioma on the upper lip, left-sided hemihypertrophy involving the entire
      body, and also evidence of left CDH (based on the results of a physical
      examination and radiographic interpretation). We present this case for the rarity
      of presentation, discuss the relationship between KTS and CDH, and the treatment
      options available with a brief review of the literature.

PMID- 23557892
TI  - Successful conservative treatment of microinvasive cervical cancer during
      pregnancy.
AB  - Cervical cancer complicated by pregnancy is a rare event. While counseling
      patients with cervical cancer during pregnancy, many factors must be considered,
      including the patient's desire to continue the pregnancy, the stage of the
      disease, and the gestational age at diagnosis. Pregnant women with microinvasive
      cervical cancer should be fully informed of all possible treatment options and
      consequences. Herein, we report the case of a woman who was diagnosed with
      microinvasive cervical cancer during pregnancy at 10 weeks of gestation. After a
      combination treatment of cervical conization, cervical cerclage, and cesarean
      section, she delivered a healthy baby and at 7 months postpartum there was no
      indication of malignancy.

PMID- 23557893
TI  - Myeloid sarcoma of the cheek and the maxillary sinus regions.
AB  - Myeloid sarcoma (MS) is a rare, extramedullary malignant tumor composed of
      immature myeloid precursor cells and myeloblast. Most MSs occur in the
      subperiosteal region of the bone, with the skull, sternum, ribs, and proximal
      portions of the long bones being the common sites of involvement. It is thought
      that the MS tumor originates in the bone marrow, and traverses the Haversian
      canals to reach the subperiosteum. Various reports have also described the
      involvement of the liver, spleen, brain, heart, pharynx, uterus, vagina, skin,
      kidney, and other soft tissues in the formation of the tumor.

PMID- 23557894
TI  - War stress may be another risk factor for eating disorders in civilians: a study
      in Lebanese university students.
AB  - OBJECTIVE: Traumatic life events are important risk factors for eating disorders
      (ED). War has been associated, in military populations, with an increased post
      service incidence of ED and an increased mean body mass index. We hypothesize
      that a modification of eating behavior (EB) related to stress during wartime may
      increase the risk of developing an ED later on among civilians exposed to war
      stress during adulthood. METHODS: This descriptive cross-sectional study was
      performed in a group of 303 undergraduate young adult students of both sexes from
      Lebanon, 6 months after the July 2006 war. Modification of EB during wartime,
      sociodemographic and other potential risk factors were assessed retrospectively.
      Students were then screened for ED using the SCOFF questionnaire. RESULTS: SCOFF
      was positive in 31.4% of the students, with a mean value 41.6% higher among
      subjects who reported an altered EB during the war. Among subjects with a
      positive SCOFF screening, 71% had experienced a change of EB during wartime.
      Alteration of EB during war was related to an odds ratio for a positive SCOFF
      screening of 2.6 (95% CI 1.54-4.34) and 1.8 (95% CI 1.01-3.21) for non-adjusted
      and adjusted analysis, respectively. CONCLUSIONS: Modification of EB related to
      stress during wartime is associated with an increased risk of eating disorders.
      Early detection and treatment of eating disorders may be improved by routinely
      evaluation of EB modification in patients with a past history of war exposure.

PMID- 23557896
TI  - Schistosomiasis among pregnant women in rural communities in Nigeria.
AB  - OBJECTIVE: To assess the epidemiology of urogenital schistosomiasis among
      pregnant women in rural communities of southwestern Nigeria. METHODS: The present
      cross-sectional epidemiologic survey of urogenital schistosomiasis was conducted
      during 2010-2011 among pregnant women in Yewa North Local Government, Ogun State,
      Nigeria. The women were microscopically screened for infection with Schistosoma
      haematobium. RESULTS: Of 313 volunteer participants, 20.8% tested positive for S.
      haematobium infection. The prevalence of infection was highest (31.5%) among
      women aged 20-24years. The infection intensity did not differ significantly
      between age groups (t=1.848, P=0.71). Primigravidae and women in the first
      trimester of pregnancy had the highest intensity of infection with 33.1 and 27.7
      eggs/10mL of urine, respectively. There was an association between disease
      prevalence and parasite intensity across the age groups (chi(2)=68.82, P=0.02).
      The prevalence of S. haematobium was not associated with age or pregnancy
      trimester (P=0.06), but associations existed between intensity of infection and
      gravidity (P=0.001). CONCLUSION: The prevalence of urogenital schistosomiasis
      among pregnant women in Nigeria was high, with younger women and primigravidae at
      the greatest risk. These data can be used to develop a schistosomiasis control
      program among pregnant women in the study area.

PMID- 23557895
TI  - Depression care and treatment in a chronically ill Medicare population.
AB  - OBJECTIVE: The purpose of this study is to examine depression care among
      chronically ill Medicare Advantage beneficiaries. METHODS: This study includes
      5898 Medicare Advantage members with a depression diagnosis enrolled between 2008
      and 2010 in a care management program. Two depression care indicators were
      created: (a) any depression care (>= 1 antidepressant prescription or >= 1
      specialty mental health visit) and (b) among those receiving any depression care,
      those receiving an antidepressant prescription for >= 90 days or >= 2 specialty
      visits. Multivariable analysis using logistic regression was used to examine
      correlates of depression care. RESULTS: Among those <65 years old, 72% received
      any depression care with 75% receiving >= 90 days of an antidepressant and/or >=
      2 specialty visits. Among >= 65 years old, 65% received any depression care with
      67% receiving >= 90 days of an antidepressant and/or >= 2 specialty visits. For
      both age groups, female gender, medical comorbidities and dual eligibility were
      positively associated with an antidepressant prescription. In the older group,
      female gender was positively associated with at least a 90-day supply of an
      antidepressant prescription, while substance use disorders were negatively
      associated with receiving a minimum of 90 days of an antidepressant. Regional
      differences and certain psychiatric comorbidities were also associated with
      receiving depression care. CONCLUSION: Two thirds of the depressed patients in
      this Medicare Advantage population received depression care. Further studies are
      needed to examine the effects of quality improvement efforts in the context of
      care management programs for chronically ill older adults.

PMID- 23557897
TI  - Use of preoperative clinicopathologic characteristics to identify patients with
      low-risk cervical cancer suitable for Piver class II radical hysterectomy.
AB  - OBJECTIVE: To investigate the long-term efficacy of Piver-Rutledge class II
      radical hysterectomy (Piver II RH) for treatment of early-stage cervical cancer
      and to identify suitable candidates for this procedure. METHODS: A retrospective
      study was conducted of 432 cervical cancer patients (tumor size <=4 cm) treated
      with Piver II RH at Sun Yat-sen University Cancer Center, Guangzhou, China,
      between January 1, 1999, and June 30, 2005. The correlation of preoperative and
      postoperative characteristics with recurrence and survival was analyzed. RESULTS:
      Median follow-up was 72 months; the overall recurrence rate was 14.6%. The 5-year
      recurrence-free survival (RFS) was 88.0% and the 5-year overall survival (OS) was
      93.0%. Significant differences were observed between patients with small (<=2 cm)
      and large (>2 cm) tumors with regard to intra-pelvic recurrence (2.5% vs 13.4%;
      P=0.001), extra-pelvic recurrence (3.4% vs 9.9%; P=0.028), RFS (95.0% vs 86.0%;
      P=0.005), and OS (95.0% vs 87.0%; P=0.005). Preoperative tumor size was the only
      factor that correlated with recurrence (P=0.018), RFS (P=0.038), and OS (P=0.029)
      in a multivariate analysis. CONCLUSION: Cervical cancer patients with tumors of 2
      cm or less were identified as candidates for Piver II RH, which promoted
      excellent local tumor control and long-term survival.

PMID- 23557898
TI  - Silicone-based surfactant degradation in aqueous media.
AB  - The increasing use of surfactants, such as modified polydimethylsiloxane-graft
      polyethylene oxide (PDMS-g-PEO), requires studies on the fate of these compounds
      in the environment, and in particular in wastewater systems. A kinetic study,
      performed under three different pH conditions (pH2, 5.3 and 11) and using (1)H
      NMR (Nuclear Magnetic Resonance), proves that hydrolysis of the siloxane chain
      takes place in all cases, with higher rates for the two extreme conditions.
      Steric exclusion chromatography (SEC) clearly showed a decrease in the average
      molecular weight of the copolymer leading to a new molecular weight distribution,
      especially in acidic conditions. Degradation products, analyzed by (29)Si NMR,
      were found to be similar whatever the degradation pathway, namely silanediols and
      cyclic volatile compounds (degradation products of PDMS) and also PEO-modified
      silanediols and cyclic compounds. After one year, the siloxane chain completely
      disappeared under acidic conditions. Real wastewater medium has a strong effect
      on polymer stability, indicating that pH is not the only parameter which
      influences degradation rate.

PMID- 23557899
TI  - An account of the events that led to full bay infilling with sulfide tailings at
      Portman (Spain), and the search for "black swans" in a potential land reclamation
      scenario.

PMID- 23557900
TI  - A test of the stability of Cd, Cu, Hg, Pb and Zn profiles over two decades in
      lake sediments near the Flin Flon Smelter, Manitoba, Canada.
AB  - Lake sediments are valuable archives of atmospheric metal deposition, but the
      stability of some element profiles may possibly be affected by diagenetic changes
      over time. In this extensive case study, the stability of sedimentary Cd, Cu, Hg,
      Pb and Zn profiles was assessed in dated sediment cores that were collected in
      2004 from four smelter-affected lakes near Flin Flon, Manitoba, which had
      previously been cored in 1985. Metal profiles determined in 1985 were in most
      cases clearly reproduced in the corresponding sediment layers in 2004, although
      small-scale spatial heterogeneity in metal distribution complicated the temporal
      comparisons. Pre-smelter (i.e. pre-1930) increases in metal profiles were likely
      the result of long-range atmospheric metal pollution, coupled with particle
      mixing at the 1930s sediment surface. However, the close agreement between key
      inflection points in the metal profiles sampled two decades apart suggests that
      metals in most of the lakes, and Hg and Zn in the most contaminated lake
      (Meridian), were stable once the sediments were buried below the surface mixed
      layer. Cadmium, Cu and Pb profiles in Meridian Lake did not agree as well between
      studies, showing evidence of upward remobilization over time. Profiles of redox
      indicator elements (Fe, Mn, Mo and U) suggested that the rate of Mn oxyhydroxide
      recycling within sediment was more rapid in Meridian Lake, which may have caused
      the Cd, Cu and Pb redistribution.

PMID- 23557901
TI  - Reproductive health of yellow perch (Perca flavescens) from a biological mercury
      hotspot in Nova Scotia, Canada.
AB  - Methylmercury (MeHg) exposure is known to adversely affect the reproductive
      health of laboratory fish, but its impacts on the sexual development of wild
      fishes are not well studied. Kejimkujik National Park and National Historic Site
      (KNPNHS) region of Nova Scotia, Canada, has been identified as a biological
      mercury (Hg) hotspot. To determine whether Hg was adversely affecting the
      reproductive health of wild yellow perch (Perca flavescens), sexually mature male
      and female perch were collected from 12 lakes within KNPNHS (mean muscle total
      Hg: 0.28-0.54 MUg/g ww). Gonadosomatic index and germ cell development of male
      and female perch were measured, as well as the plasma 17 beta-estradiol
      concentrations of females. These endpoints were compared between lakes, and were
      related to Hg concentrations measured in perch muscle and liver tissues. Our
      results indicate that the reproductive health of male and female perch was not
      adversely impacted by Hg, although a positive relationship existed between the
      proportions of primary spermatocytes in male testes and muscle total Hg
      concentrations. Perch were sampled at an early stage of recrudescence, and the
      tissue Hg concentrations in these perch were generally lower than those in
      laboratory studies reporting impacts on reproductive health, both of which may
      explain the absence of effects. Based on the measured endpoints, it appears that
      reproduction in perch was not affected at Hg concentrations known to affect fish
      eating wildlife.

PMID- 23557902
TI  - Candidate biomarker discovery for angiogenesis by automatic integration of
      Orbitrap MS1 spectral- and X!Tandem MS2 sequencing information.
AB  - Candidate protein biomarker discovery by full automatic integration of Orbitrap
      full MS1 spectral peptide profiling and X!Tandem MS2 peptide sequencing is
      investigated by analyzing mass spectra from brain tumor samples using Peptrix.
      Potential protein candidate biomarkers found for angiogenesis are compared with
      those previously reported in the literature and obtained from previous Fourier
      transform ion cyclotron resonance (FT-ICR) peptide profiling. Lower mass accuracy
      of peptide masses measured by Orbitrap compared to those measured by FT-ICR is
      compensated by the larger number of detected masses separated by liquid
      chromatography (LC), which can be directly linked to protein identifications. The
      number of peptide sequences divided by the number of unique sequences is
      9248/6911~1.3. Peptide sequences appear 1.3 times redundant per up-regulated
      protein on average in the peptide profile matrix, and do not seem always up
      regulated due to tailing in LC retention time (40%), modifications (40%) and mass
      determination errors (20%). Significantly up-regulated proteins found by
      integration of X!Tandem are described in the literature as tumor markers and some
      are linked to angiogenesis. New potential biomarkers are found, but need to be
      validated independently. Eventually more proteins could be found by actively
      involving MS2 sequence information in the creation of the MS1 peptide profile
      matrix. 

PMID- 23557903
TI  - Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated
      lymphoid tissue type in the central nervous system (MZL CNS) presented as
      traumatic subdural hematoma and subarachnoid bleeding - case report.
AB  - The study describes a very rare case of primary extranodal marginal zone Bcell
      lymphoma of the central nervous system (MZL CNS) with an unusual clinical and
      radiological presentation mimicking subarachnoid bleeding and subdural hematoma
      (SDH) after head injury. The patient presented symptoms which had commenced 3
      weeks earlier: a gradually-progressing headache associated with periodic right
      sided cramp of the face muscles and numbness of the right upper limb. During
      urgent craniotomy for drainage of the presumed SDH, a tumor mass
      histopathologically and immunohistochemically matching marginal zone B-cell
      lymphoma was found. Molecular analysis confirmed monoclonal immunoglobulin heavy
      chain gene (IgH) rearrangement; the patient had previously suspected nodal
      lymphoma because of cervical lymphadenopathy, but histopathological,
      immunohistochemical and molecular examination excluded malignant lymphoma. The
      patient underwent successful radiotherapy, and achieved complete response. At
      present, no evidence of either systemic disease or lymph node enlargement has
      been found. The recognition of an indolent type of lymphoma in a rare anatomical
      localization is very important due to the proper management of the patient. 

PMID- 23557904
TI  - Myoepithelioma of the cerebellopontine angle: a previously not documented benign
      salivary gland-type neoplasm within the cranium.
AB  - Myoepithelioma is a dimorphic neoplasm with contractile-epithelial phenotype,
      originally interpreted as deriving from, but not actually restricted to the
      salivary glands. As a novel addition to the list of exquisitely rare intracranial
      salivary gland-type tumors and tumor-like lesions, we report on an example of
      myoepithelioma encountered in the left cerebellopontine angle of a 32-year-old
      male. Clinically presenting with ataxia and dizziness, this extraaxial mass of 4
      * 3.5 * 3 cm was surgically resected, and the patient is alive 6 years
      postoperatively. Histologically, the tumor exhibited a continuum ranging from
      compact fascicles of spindle cells to epithelial nests and trabeculae partitioned
      by hyalinized septa, while lacking tubular differentiation. Regardless of
      architectural variations, there was robust immunoexpression of S100 protein,
      smooth muscle actin, GFAP, cytokeratin, and vimentin. Cytologic atypia tended to
      be modest throughout, and the MIB1 labeling index averaged less than 1%.
      Fluorescent in situ hybridization indicated no rearrangement of the EWSR1 locus.
      We interpret these results to suggest that myoepithelioma of the posterior fossa 
      along with related salivary epithelial tumors in this ostensibly incongruous
      locale - may possibly represent analogous neoplasms to their orthotopic
      counterparts, ones arising within aberrant salivary anlagen. The presence of the
      latter lends itself to being mechanistically accounted for by either postulating
      placodal remnants in the wake of branchial arch development, or linking them to
      exocrine glandular nests within endodermal cysts. Alternatively, myoepithelioma
      at this site could be regarded as a non tissue-specific lesion similar to its
      relatives ubiquitously occurring in the soft parts.

PMID- 23557905
TI  - Primary intraventricular gliosarcoma.

PMID- 23557906
TI  - Extensive anterior skull-base mesenchymal chondrosarcoma: unusual cause of
      multiple indolent masses on the forehead.
AB  - Primary intracranial occurrence of an extraskeletal mesenchymal chondrosarcoma
      (MC) is unusual. The commonly involved sites are the orbit, clivus and temporo
      occipital junction. Occurrence of the lesion in the anterior skull-base (ASB) in
      an infiltrative manner and with extra-calvarial involvement, is anecdotal. We
      report the case of a 35-year-old woman who presented with two indolent swellings
      on the forehead for a duration of 1 year. Examination revealed impaired visual
      acuity and complete external ophthalmoplegia in the right eye and 5 * 6 cm and 2
      * 3 cm sized hard masses on the forehead. CT and MRI revealed a large, intensely
      enhancing ASB mass with extensions into the right orbit, ethmoid sinus, nasal
      cavity, and anteriorly, into the subcutaneous tissue of the frontal scalp through
      erosions in the bone. At surgery via a right frontal recraniotomy, the lesion was
      found to be firm and very vascular. Owing to its extreme vascularity,
      decompression was limited to excision of the intracranial and extra-calvarial
      components of the lesion. Histopathology was consistent with the diagnosis of MC.
      The patient was advised a second stage surgery for excision of the residual
      lesion. She, however, opted for radiation therapy and was lost to follow-up. This
      report, with one of the most extensive ASB MCs described to date, adds to the
      list of rare differentials of indolent forehead masses in the diagnostic
      armamentarium of the neuropathologist. 

PMID- 23557907
TI  - Regulation of feeding behavior, gastrointestinal function and fluid homeostasis
      by apelin.
AB  - Apelin was first identified and characterized from bovine stomach extracts as an
      endogenous ligand for the APJ receptor. Apelin/APJ system is abundantly present
      in peripheral tissues and central nervous system. Apelin plays a broad role in
      regulating physiological and pathological functions. Recently, many reports have
      showed the effects of apelin on feeding behavior, however the results are
      inconsistent, due to different administration routes, animal species, forms of
      apelin, etc. Apelin has been involved in stimulating gastric cell proliferation,
      cholecystokinin (CCK) secretion, histamine release, gastric acid and bicarbonate
      secretion, and regulation of gastrointestinal motility. In addition, apelin
      produced regulatory effects on drinking behavior, diuresis, arginine vasopressin
      (AVP) release and glucocorticoids secretion. This article reviews the role of
      apelin on feeding behavior, gastrointestinal function and fluid homeostasis.

PMID- 23557908
TI  - Healthcare providers' knowledge and attitudes about rapid tissue donation (RTD):
      phase one of establishing a rapid tissue donation programme in thoracic oncology.
AB  - In preparation for the development of a rapid tissue donation (RTD) programme, we
      surveyed healthcare providers (HCPs) in our institution about knowledge and
      attitudes related to RTD with lung cancer patients. A 31-item web based survey
      was developed collecting data on demographics, knowledge and attitudes about RTD.
      The survey contained three items measuring participants' knowledge about RTD,
      five items assessing attitudes towards RTD recruitment and six items assessing
      HCPs' level of agreement with factors influencing decisions to discuss RTD.
      Response options were presented on a 5-point Likert scale. Ninety-one HCPs
      participated in the study. 66% indicated they had never heard of RTD prior to the
      survey, 78% rated knowledge of RTD as none or limited and 95.6% reported not
      having ethical or religious concerns about discussing RTD with patients. The
      majority were either not comfortable (17.8%) or not sure if they felt comfortable
      discussing RTD with cancer patients (42.2%). 56.1% indicated their knowledge of
      RTD would play an integral role in their decision to discuss RTD with patients.
      71.4% reported concerns with RTD discussion and the emotional state of the
      patient. Physicians and nurses play an important role in initiating conversations
      about recruitment and donation to research that can ultimately influence uptake.
      Increasing HCP knowledge about RTD is a necessary step towards building an RTD
      programme. Our study provides important information about characteristics
      associated with low levels of knowledge and practice related to RTD where
      additional education and training may be warranted. 

PMID- 23557909
TI  - The neglected repercussions of a physician advertising ban.
AB  - Although the adverse implications of physician advertising are the subject of a
      fierce and sustained debate, there is almost no scholarly discussion on the
      ethical repercussions of physician advertising bans. The present paper draws
      attention to these repercussions as they exist today in most of the world, with
      particular focus on three serious implications for the public: (a) uncertainty
      about the physician's interests, namely, that patients must trust the physician
      to put patient wellbeing ahead of possible gains when taking medical decisions;
      (b) uncertainty about alternative treatments, namely, that patients must trust in
      the physician's treatment decisions; and (c) uncertainty about the exclusive
      patient-physician relationship, namely, that patients must develop and maintain a
      good relationship with one physician. Physician advertising bans continue to tell
      the public in most of the modern world that these are irrelevant or inappropriate
      issues, meaning that they are effectively left to the public to resolve.

PMID- 23557910
TI  - Family presence during cardiopulmonary resuscitation: who should decide?
AB  - Whether to allow the presence of family members during cardiopulmonary
      resuscitation (CPR) has been a highly contentious topic in recent years. Even
      though a great deal of evidence and professional guidelines support the option of
      family presence during resuscitation (FPDR), many healthcare professionals still
      oppose it. One of the main arguments espoused by the latter is that family
      members should not be allowed for the sake of the patient's best interests,
      whether it is to increase his chances of survival, respect his privacy or leave
      his family with a last positive impression of him. In this paper, we examine the
      issue of FPDR from the patient's point of view. Since the patient requires CPR,
      he is invariably unconscious and therefore incompetent. We discuss the Autonomy
      Principle and the Three-Tiered process for surrogate decision making, as well as
      the Beneficence Principle and show that these are limited in providing us with an
      adequate tool for decision making in this particular case. Rather, we rely on a
      novel principle (or, rather, a novel specification of an existing principle) and
      a novel integrated model for surrogate decision making. We show that this model
      is more satisfactory in taking the patient's true wishes under consideration and
      encourages a joint decision making process by all parties involved. 

PMID- 23557911
TI  - Incentives for postmortem organ donation: ethical and cultural considerations.

PMID- 23557913
TI  - In vitro eugenics.
AB  - A series of recent scientific results suggest that, in the not-too-distant
      future, it will be possible to create viable human gametes from human stem cells.
      This paper discusses the potential of this technology to make possible what I
      call 'in vitro eugenics': the deliberate breeding of human beings in vitro by
      fusing sperm and egg derived from different stem-cell lines to create an embryo
      and then deriving new gametes from stem cells derived from that embryo. Repeated
      iterations of this process would allow scientists to proceed through multiple
      human generations in the laboratory. In vitro eugenics might be used to study the
      heredity of genetic disorders and to produce cell lines of a desired character
      for medical applications. More controversially, it might also function as a
      powerful technology of 'human enhancement' by allowing researchers to use all the
      techniques of selective breeding to produce individuals with a desired genotype. 

PMID- 23557912
TI  - Achieving new levels of recall in consent to research by combining remedial and
      motivational techniques.
AB  - INTRODUCTION: Research supports the efficacy of both a remedial consent procedure
      (corrected feedback (CF)) and a motivational consent procedure (incentives) for
      improving recall of informed consent to research. Although these strategies were
      statistically superior to standard consent, effects were modest and not
      clinically significant. This study examines a combined incentivised consent and
      CF procedure that simplifies the cognitive task and increases motivation to learn
      consent information. METHODS: We randomly assigned 104 individuals consenting to
      an unrelated host study to a consent as usual (CAU) condition (n=52) or an
      incentivised CF (ICF) condition (n=52). All participants were told they would be
      quizzed on their consent recall following their baseline assessment and at 4
      monthly follow-ups. ICF participants were also informed that they would earn $5
      for each correct answer and receive CF as needed. RESULTS: Quiz scores in the two
      conditions did not differ at the first administration (p=0.39, d=0.2); however,
      ICF scores were significantly higher at each subsequent administration (second:
      p=0.003, Cohen's d=0.6; third: p<0.0001, d=1.4; fourth: p<0.0001, d=1.6; fifth:
      p<0.0001, d=1.8). CONCLUSIONS: The ICF procedure increased consent recall from
      72% to 83%, compared with the CAU condition in which recall decreased from 69% to
      59%. This supports the statistical and clinical utility of a combined remedial
      and motivational consent procedure for enhancing recall of study information and
      human research protections.

PMID- 23557914
TI  - Capillaroscopic Skin Ulcers Risk Index (CSURI) calculated with different
      videocapillaroscopy devices: how its predictive values change.
AB  - INTRODUCTION: Digital ulcers (DU) occur in about 50% of systemic sclerosis (SSc)
      patients. Scleroderma DU are responsible for chronic pain and disability with the
      need of systemic and local treatments. Recently, capillaroscopic skin ulcer risk
      index (CSURI) has been validated as useful tool in predicting the appearance of
      new scleroderma ulcers and/or persistence of non-healing lesions, within 3 months
      from capillaroscopy evaluation. OBJECTIVES: Since the image length of 1.57 mm
      might represent a critical factor for CSURI calculation, the present study aimed
      to evaluate the reliability of CSURI using three different videocapillaroscopy
      devices with distinct image widths. METHODS: One hundred and seventy-six
      unselected SSc patients were consecutively enrolled for the study during a six
      month period, using three different capillaroscopy devices (image widths of 1.33,
      1.57, and 1.70 mm). RESULTS: After a three month-follow-up new DU or persisting
      non-healing ulcers were observed in 46/176 patients (26.1%). The receiver
      operating characteristic curve analysis for CSURI showed an area under curve
      respectively of 0.705 for the image width of 1.33 mm, 0.786 for the image of 1.70
      mm, and 0.888 for the image width of 1.57 mm. CONCLUSIONS: The good sensitivity,
      specificity and positive predictive value of CSURI was confirmed in the whole
      patients' series, as well as in the three subgroups on different image widths
      obtained with various available devices. In addition, the negative predictive
      value of the capillaroscopic index remained very high regardless of the picture
      length adopted.

PMID- 23557915
TI  - Down-regulation of miR-223 contributes to the formation of Gottron's papules in
      dermatomyositis via the induction of PKCE.
AB  - BACKGROUND: Dermatomyositis (DM) is characterized by skin manifestations
      accompanying and preceding muscle weakness. Gottron's papules, one of the skin
      manifestations, are of great diagnostic value because they are specific to DM.
      However, the pathogenesis of Gottron's papules remains unclear. OBJECTIVES: We
      investigated the expression pattern of miRNAs in Gottron's papules of DM patients
      and evaluated the possibility that miRNAs play a role in its pathogenesis.
      MATERIALS AND METHODS: miRNAs were extracted from skin tissues and sera of
      patients with DM, clinically amyopathic DM (CADM) and healthy controls. To
      identify pathogenic miRNAs, we performed miRNA PCR array analysis. The results
      were confirmed by in situ hybridization, immunohistochemistry, immunoblotting and
      transient transfection of siRNAs or miRNA inhibitors. RESULTS: PCR array analysis
      using tissue miRNAs demonstrated the miR-223 level was markedly decreased in
      Gottron's papules of DM and CADM in vivo, but not in psoriasis skin. The protein
      expression of PKCE, a predicted target of miR-223, was increased in DM/CADM skin.
      The transfection of a specific inhibitor of miR-223 in keratinocytes led to up
      regulation of the PKCE protein, and resulted in increased cell proliferation. On
      the other hand, cell numbers were significantly decreased when cells were
      transfected with siRNA for PKCE. The serum miR-223 concentration was decreased in
      DM/PM patients, particularly in CADM patients, compared with healthy controls.
      CONCLUSIONS: A decreased miR-223 expression and the subsequently increased PKCE
      levels may therefore play a key role in the pathogenesis of Gottron's papules.

PMID- 23557916
TI  - Extranodal Rosai-Dorfman disease involving the pulmonary artery.

PMID- 23557917
TI  - Video-assisted thoracoscopic surgery sleeve lobectomy with bronchoplasty: an
      improved operative technique.
AB  - OBJECTIVES: We summarize our experiences of video-assisted thoracoscopic surgery
      (VATS) sleeve lobectomy with bronchoplasty for non-small-cell lung cancer and
      discuss the indications and technical details of the operation. METHODS: From
      September 2011 to December 2012, 15 patients underwent VATS sleeve lobectomy with
      bronchoplasty at our institution (right upper lobe 10, right middle and lower
      lobes 1, left lower lobe 2 and left upper lobe 2), with mediastinal
      lymphadenectomy. Three incisions were utilized. The utility incision was made at
      the fourth intercostal space, anterior axillary line. Simple continuous and
      simple interrupted suturing of the membranous and cartilaginous portions of the
      bronchus were performed for the anastomosis. RESULTS: All procedures were
      uneventful, with a median operative time of 165 min, a median bronchial
      anastomosis time of 44 min and a median blood loss of 150 ml. There were no
      conversions to thoracotomy. There were 14 squamous carcinomas and 1
      adenocarcinoma. All patients recovered well, and 1 experienced a minor
      complication. The median duration of chest tube drainage was 5.4 days, and the
      median length of hospital stay was 7 days. All patients were followed
      postoperatively for a range of 1-16 months without tumour recurrence.
      CONCLUSIONS: VATS sleeve lobectomy with bronchoplasty is safe and effective. The
      utility incision placed at the fourth intercostal space, anterior axillary line,
      is convenient for the anastomosis, and the suturing technique is expeditious and
      secure. Preserving the azygos vein does not compromise exposure for the
      anastomosis. This technique is very suitable for centrally located lung cancers
      <3 cm in diameter, particularly when the cancers are located within the brachial
      lumen.

PMID- 23557918
TI  - Pulmonary resections following prior definitive chemoradiation therapy are
      associated with acceptable survival.
AB  - OBJECTIVES: The benefits of salvage resection for lung cancer recurrence
      following high-dose curative-intent chemoradiation therapy are unclear. We
      assessed survival after salvage lung resection following definitive
      chemoradiation. METHODS: Medical records of patients undergoing lung cancer
      resections at our institution following definitive chemoradiation therapy were
      reviewed from June 2006 to August 2012. A multivariate Cox proportional model was
      used to assess the factors associated with improved survival. RESULTS: Fourteen
      patients had chemoradiation therapy before lung resection (pneumonectomy,
      lobectomy or segmentectomy). Pretherapy cancer stage was Stage III in 11
      patients, Stage IV in 2 and Stage II in 1. Postoperative 2-year survival was 49%.
      Patients had a median disease-free interval before resection of 33 months. No
      variables were found to be associated with improved post-chemoradiation survival
      from the time of definitive treatment or postoperative survival. Complications
      occurred in 6 (43%) patients, with 2 of those complications directly attributable
      to post-chemoradiation changes. There were no perioperative deaths within 90
      days. CONCLUSIONS: Salvage lung resection for recurrent lung cancer following
      definitive chemoradiation therapy is feasible and is associated with
      postoperative survival and complication rates that are reasonable.

PMID- 23557920
TI  - Management of lung cancer in a situs viscerum inversus patient.

PMID- 23557919
TI  - Risk factors for both recurrence and survival in patients with pathological stage
      I non-small-cell lung cancer.
AB  - OBJECTIVES: Even after curative resection, a significant fraction of patients
      with stage I non-small-cell lung cancer (NSCLC) die primarily because of systemic
      relapse. The purpose of the present study was to investigate the risk factors for
      both recurrence and poor survival in patients with pathological (p-) stage I
      NSCLC. METHODS: We retrospectively reviewed 467 consecutive patients from a
      single institution with completely resected p-stage I NSCLC. Patients with
      multiple lung tumours or malignancies from other organs and those who had
      undergone preoperative therapies were excluded. The correlation between
      clinicopathological factors and surgical outcomes, including disease-free
      survival (DFS) and overall survival (OS), was analysed. The clinicopathological
      factors examined were age, gender, smoking history, serum carcinoembryonic
      antigen (CEA) levels, serum cytokeratin 19 fragment levels, surgical procedure,
      tumour histology, p-stage, angiolymphatic invasion and differentiation grade.
      RESULTS: The 5-year DFS and OS rates of the total study population were 91.4 and
      92.8%, respectively. Multivariate analysis results indicated that high serum CEA
      levels (>5.0 ng/ml) and p-stage IB were independent factors for recurrence,
      whereas older age (>70 years), high serum CEA levels and p-stage IB were
      independent factors for poor survival. The risks of recurrence and death in
      patients with both high serum CEA levels and p-stage IB was 10.3 and 5.2 times
      higher than those observed in patients with both normal serum CEA levels and p
      stage IA, respectively. CONCLUSIONS: High serum CEA levels and p-stage IB were
      independent factors for both recurrence and poor survival in p-stage I NSCLC
      patients.

PMID- 23557921
TI  - Giant ascending aorta saccular aneurysm in a patient affected by Turner syndrome.

PMID- 23557923
TI  - Escherichia coli antimicrobial resistance increased faster among geriatric
      outpatients compared with adult outpatients in the USA, 2000-10.
AB  - OBJECTIVES: Few studies have examined Escherichia coli antimicrobial resistance
      across age groups over time. The objective of this study was to compare urinary
      E. coli antimicrobial resistance trends among adult and geriatric outpatients
      from 2000 to 2010. METHODS: Antimicrobial susceptibility results for E. coli
      urine isolates from adult (aged 16-64 years) and geriatric (aged >=65 years)
      outpatients were analysed using data from The Surveillance Network Database-USA.
      RESULTS: Susceptibility test results from adult (n = 6 412 025) and geriatric (n
      = 3 395 297) outpatients showed that E. coli antimicrobial resistance increased
      faster among geriatric outpatients for all agents studied. The greatest increases
      in resistance over the study time period were for ciprofloxacin (9.4% and 23.5%
      increases among adult and geriatric individuals, respectively),
      trimethoprim/sulfamethoxazole (4.3% and 10.5%) and ampicillin (2.0% and 13.6%).
      CONCLUSIONS: Urinary E. coli antimicrobial resistance increased faster among
      geriatric outpatients than adult outpatients in the USA. Rising antimicrobial
      resistance disproportionately affects geriatric populations and presents a threat
      to public health.

PMID- 23557922
TI  - Lack of upward creep of glycopeptide MICs for methicillin-resistant
      Staphylococcus aureus (MRSA) isolated in the UK and Ireland 2001-07--authors'
      response.

PMID- 23557924
TI  - Rapid degradation of Streptococcus pyogenes biofilms by PlyC, a bacteriophage
      encoded endolysin.
AB  - OBJECTIVES: Streptococcus pyogenes, or Group A streptococcus (GAS), has a
      propensity to colonize human tissues and form biofilms. Significantly, these
      biofilms are a contributing mechanism of antibiotic treatment failure in
      streptococcal disease. In this study, we evaluate a streptococcal-specific
      bacteriophage-encoded endolysin (PlyC), which is known to lyse planktonic
      streptococci, on both static and dynamic streptococcal biofilms. METHODS: PlyC
      was benchmarked against antibiotics for MIC, MBC and minimum biofilm eradication
      concentration (MBEC). A biomass eradication assay based on crystal violet
      staining of the biofilm matrix was also used to quantify the anti-biofilm
      properties of PlyC. Finally, conventional fluorescence microscopy and laser
      scanning confocal microscopy were used to study the effects of PlyC on static and
      dynamic biofilms of GAS. RESULTS: PlyC and antibiotics had similar MIC (range
      0.02-0.08 mg/L) and MBC (range 0.02-1.25 mg/L) values on planktonic GAS. However,
      when GAS grew in biofilms, the MBEC values for antibiotics rose to clinically
      resistant values (>=400 mg/L) whereas PlyC had MBEC values two orders of
      magnitude lower by mass and four orders of magnitude lower by molarity than the
      conventional antibiotics. Laser scanning confocal microscopy revealed that PlyC
      destroys the biofilm as it diffuses through the matrix in a time-dependent
      fashion. CONCLUSIONS: Our findings indicate that while streptococcal cells within
      a biofilm rapidly become refractory to traditional antibiotics, the biofilm
      matrix is readily destroyed by the lytic actions of PlyC.

PMID- 23557925
TI  - Impact of ertapenem use on Pseudomonas aeruginosa and Acinetobacter baumannii
      imipenem susceptibility rates: collateral damage or positive effect on hospital
      ecology?
AB  - BACKGROUND: Conflicting evidence has been reported on the impact of ertapenem use
      on the susceptibility of Pseudomonas spp. to group 2 carbapenems. No extensive
      data for Acinetobacter baumannii are currently available. METHODS: A
      retrospective time-series segmented regression analysis was conducted in a
      tertiary centre from January 2001 to December 2011. Ertapenem was introduced in
      January 2005. Antimicrobial drug use was defined as the number of defined daily
      doses/100 patient-days (DDDs/100 PDs). Susceptibility (CLSI) was measured in
      terms of proportion and incidence density. RESULTS: Mean monthly use of imipenem
      was 2.9 +/- 0.9 DDDs/100 PDs, as compared with 1.2 +/- 0.7 DDDs/100 PDs for
      meropenem and 1.0 +/- 0.7 DDDs/100 PDs for ertapenem (after its introduction).
      After ertapenem adoption, a downward trend was seen in the use of imipenem (P =
      0.016) and ciprofloxacin (P = 0.004). A total of 6272 Pseudomonas aeruginosa and
      1093 A. baumannii isolates were evaluated. Susceptibility of P. aeruginosa to
      imipenem improved after ertapenem introduction, both according to the proportion
      of susceptible isolates (P = 0.002) and to the incidence density of resistance (P
      <= 0.001). No significant change was seen in A. baumannii susceptibility to
      imipenem (P = 0.772). By multiple linear regression analysis, the incidence
      density of imipenem-resistant P. aeruginosa increased with the use of imipenem (P
      = 0.003) and ciprofloxacin (P = 0.008). Occurrence of outbreaks (P <= 0.001) and
      use of gentamicin (P = 0.007) were associated with A. baumannii resistance to
      imipenem. CONCLUSIONS: Use of ertapenem was directly associated with a downward
      trend in the use of imipenem and ciprofloxacin, which may have contributed to
      improve the susceptibility of P. aeruginosa to imipenem. Ertapenem use had no
      impact on the susceptibility of A. baumannii to imipenem.

PMID- 23557926
TI  - Prevalence and mechanisms of resistance to carbapenems in Enterobacteriaceae
      isolates from 24 hospitals in Belgium.
AB  - OBJECTIVES: To determine the point prevalence of carbapenem-non-susceptible
      Enterobacteriaceae (CNSE) and carbapenemase-producing Enterobacteriaceae (CPE)
      isolates among hospitalized patients in Belgium. METHODS: Twenty-four hospital
      based laboratories prospectively collected 200 non-duplicated Enterobacteriaceae
      isolates from clinical specimens of hospitalized patients over a 2 month period.
      All isolates were screened locally for decreased susceptibility to carbapenem
      drugs using a disc diffusion method according to CLSI interpretative criteria.
      CNSE strains were referred centrally for confirmation of carbapenemase by
      phenotypic and molecular testing. RESULTS: From February to April 2012, 158 of
      the 4564 screened Enterobacteriaceae isolates were categorized as non-susceptible
      to carbapenems, resulting in a point prevalence of CNSE of 3.5% (95% CI: 2.9%
      4.2%; range per centre: 0.5%-8.5%). Of the 125 referred CNSE isolates, 11
      Klebsiella pneumoniae isolates [OXA-48 (n = 7), KPC type (n = 3) and NDM type (n
      = 1)], 1 OXA-48-positive Escherichia coli isolate and 1 KPC-positive Klebsiella
      oxytoca isolate were detected in eight hospitals. None of the 72 carbapenem-non
      susceptible Enterobacter spp. isolates were confirmed as CPE. The minimal
      estimated point prevalence of CPE isolates was 0.28% (13/4564; 95% CI: 0.13%
      0.44%) overall (range per centre: 0%-1.5%). CONCLUSIONS: Despite the overall low
      prevalence of CNSE found in this study, the detection of CPE isolates in one
      third of the participating centres raises concerns and highly suggests the spread
      and establishment of CPE in Belgian hospitals.

PMID- 23557927
TI  - An elevated pro-inflammatory cytokine response is linked to development of
      amphotericin B-induced nephrotoxicity.
AB  - OBJECTIVES: The underlying mechanism for amphotericin B-induced acute kidney
      injury (AKI) remains poorly understood and may be immunologically mediated. We
      assessed whether the development of nephrotoxicity is linked to a distinct
      cytokine profile in patients receiving amphotericin B deoxycholate (AmBD).
      PATIENTS AND METHODS: In 58 patients who received AmBD, circulating serum
      interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2
      of antifungal treatment and correlated to the development of renal impairment.
      The Cox proportional hazards model approach was adopted for analysis. RESULTS:
      The P value was 0.026 for the overall effect of IL-6 on time to development of
      AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment
      (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2)
      correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR)
      6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly,
      persistently increasing IL-8 levels were linked to a 3.84-fold increased
      likelihood of AKI. CONCLUSIONS: In patients receiving AmBD, persistence of an
      elevated pro-inflammatory cytokine milieu is associated with a predisposition to
      drug-related kidney injury.

PMID- 23557928
TI  - Evaluation of antimicrobial activity of ceftaroline against Clostridium difficile
      and propensity to induce C. difficile infection in an in vitro human gut model.
AB  - OBJECTIVES: To examine the effects of exposure to ceftaroline or ceftriaxone on
      the epidemic Clostridium difficile strain PCR ribotype 027 and the indigenous gut
      microflora in an in vitro human gut model. Additionally, the MICs of ceftriaxone
      and ceftaroline for 60 C. difficile isolates were determined. METHODS: Two triple
      stage chemostat gut models were primed with human faeces and exposed to
      ceftaroline (10 mg/L, twice daily, 7 days) or ceftriaxone (150 mg/L, once daily,
      7 days). Populations of indigenous gut microorganisms, C. difficile total viable
      counts, spore counts, cytotoxin titres and antimicrobial concentrations were
      monitored throughout. MICs were determined by a standard agar incorporation
      method. RESULTS: In the gut model, both ceftaroline and ceftriaxone induced C.
      difficile spore germination, proliferation and toxin production, although
      germination occurred 5 days later in the ceftaroline-exposed model. Toxin
      detection was sustained until the end of the experimental period in both models.
      No active antimicrobial was detected in vessel 3 of either model, although
      inhibitory effects on microflora populations were observed. Ceftaroline was ~8
      fold more active against C. difficile than ceftriaxone (geometric mean MICs, 3.38
      versus 28.18 mg/L; MIC90s, 4 versus 64 mg/L; and MIC ranges, 0.125-16 versus 8
      128 mg/L). CONCLUSIONS: Ceftaroline, like ceftriaxone, can induce simulated C.
      difficile infection in a human gut model. However, low in vivo gut concentrations
      of ceftaroline and increased activity against C. difficile in comparison with
      ceftriaxone mean that the true propensity of this novel cephalosporin to induce
      C. difficile infection remains unclear.

PMID- 23557929
TI  - Detection of NDM-7 in Germany, a new variant of the New Delhi metallo-beta
      lactamase with increased carbapenemase activity.
AB  - OBJECTIVES: This study characterized a new variant of the New Delhi metallo-beta
      lactamase (NDM). METHODS: A multidrug-resistant Escherichia coli isolate was
      recovered from the wounds, throat and rectum of a Yemeni patient who presented at
      the Frankfurt University Hospital in Germany. The presence of beta-lactamase
      genes was analysed by PCR and sequencing. The isolate was further characterized
      by susceptibility testing, conjugation and transformation assays and plasmid
      analysis. RESULTS: The E. coli isolate was resistant to all beta-lactams
      including carbapenems. By PCR analysis, the beta-lactamase genes blaCMY-2, blaCTX
      M-15, blaTEM-1 and blaNDM were identified. Sequencing revealed a blaNDM gene that
      differed from blaNDM-1 by two point mutations at positions 388 (G->A) and 460 (A
      >C) corresponding to amino acid substitutions Asp130Asn and Met154Leu,
      respectively. This NDM variant was identified as NDM-7. The blaNDM-7 gene was
      located on a self-transferable IncX3 plasmid of 60 kb. E. coli TOP10
      transformants harbouring NDM-7 showed higher MICs of beta-lactams including
      carbapenems compared with transformants harbouring NDM-1. Multilocus sequence
      typing analysis revealed that the E. coli isolate belonged to a novel sequence
      type (ST599). CONCLUSIONS: This study identified a novel NDM variant in E. coli,
      NDM-7, possessing a high ability to hydrolyse beta-lactam antibiotics. Given the
      diversity of NDM variants located on self-transferable plasmids found in
      different Gram-negative species and isolated in different countries, the blaNDM
      gene will most likely efficiently disseminate worldwide.

PMID- 23557930
TI  - Safety, tolerability and pharmacokinetics of repeat dosing of the antibiotic
      GSK1322322, a peptide deformylase inhibitor: a randomized placebo-controlled
      study.
AB  - OBJECTIVES: GSK1322322 is a potent inhibitor of peptide deformylase, an essential
      bacterial enzyme required for protein maturation. In this two-part, double-blind,
      randomized, placebo-controlled, Phase 1 study (study identifier: PDF112668), the
      safety, tolerability and pharmacokinetics of single and repeat oral-dose
      GSK1322322 (500-1500 mg) in healthy adult and elderly volunteers were evaluated.
      PATIENTS AND METHODS: Part A included GSK1322322 doses of 500, 750, 1000 and 1500
      mg in healthy adults; Part B evaluated 1000 mg of GSK1322322 in healthy elderly
      volunteers. Volunteers received a single morning dose of a powder-in-bottle
      formulation of GSK1322322 or placebo on day 1, no dosing on day 2 and twice-daily
      dosing on days 3-12. RESULTS: Of 52 enrolled volunteers, 40 and 12 volunteers
      were treated with GSK1322322 and placebo, respectively. Mean plasma GSK1322322
      trough concentration increased with increasing dose and reached steady-state
      after 2 days of repeat dosing. After single dosing of GSK1322322, maximum plasma
      concentration and exposure (AUC) were dose proportional from 500 to 1500 mg.
      However, after repeat dosing, AUC values at steady-state increased slightly more
      than proportionally, possibly because of a slightly longer terminal elimination
      t&frac12; after repeat dosing (compared with single-dose t&frac12;) at higher
      doses (1000 and 1500 mg). There was no age effect or diurnal variation in the
      GSK1322322 pharmacokinetic profile. GSK1322322 was generally well tolerated-all
      adverse events were mild to moderate in intensity. CONCLUSIONS: Repeat oral
      GSK1322322 (500-1500 mg) for 10 days was well tolerated. These data warrant
      further clinical investigation of GSK1322322.

PMID- 23557931
TI  - Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal
      transplant recipients using a joint modeling approach.
AB  - This study aimed to investigate the association between longitudinal exposure to
      mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after
      renal transplantation, and to propose MPA exposure targets conditionally to this
      association. A joint model, adjusted for monitoring strategy (fixed-dose versus
      concentration-controlled) and recipient age, was developed; it combined a mixed
      effects model to describe the whole pattern of MPA exposure (i.e. area under the
      concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were
      determined using time-dependent receiver-operating characteristics (ROC) curves.
      Data from 490 adult renal-transplant recipients, representative of the general
      population of adult renal-transplant patients (i.e. including patients considered
      at low immunological risk-enrolled in the OPERA trial as well as second renal
      transplant and patients co-treated by either cyclosporine or tacrolimus), were
      analyzed. A significant association was found between the longitudinal exposure
      to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A
      significant positive correlation was observed between time post-transplantation
      and ROC thresholds which increased in average from 35 mg h/L in the first days to
      41 mg h/L beyond six months post-transplantation (p<0.001). Using a new modeling
      approach which recognizes the repeated measures in a same patient, this study
      supports the association between MPA exposure and AR.

PMID- 23557932
TI  - Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug
      sensitive and resistant colon cancer cells.
AB  - 5-Fluorouracil (5-FU) is the most used chemotherapeutic agent in colorectal
      cancer. However, resistance to this drug is relatively frequent, and new
      strategies to overcome it are urgently needed. The aim of this work was to
      determine the antitumor properties of a supercritical fluid rosemary extract
      (SFRE), alone and in combination with 5-FU, as a potential adjuvant therapy
      useful for colon cancer patients. This extract has been recognized as a healthy
      component by the European Food Safety Authority (EFSA). The effects of SFRE both
      alone and in combination with 5-FU were evaluated in different human colon cancer
      cells in terms of cell viability, cytotoxicity, and cell transformation.
      Additionally, colon cancer cells resistant to 5-FU were used to assay the effects
      of SFRE on drug resistance. Finally, qRT-PCR was performed to ascertain the
      mechanism by which SFRE potentiates the effect of 5-FU. Our results show that
      SFRE displays dose-dependent antitumor activities and exerts a synergistic effect
      in combination with 5-FU on colon cancer cells. Furthermore, SFRE sensitizes 5-FU
      resistant cells to the therapeutic activity of this drug, constituting a
      beneficial agent against both 5-FU sensitive and resistant tumor cells. Gene
      expression analysis indicates that the enhancement of the effect of 5-FU by SFRE
      might be explained by the downregulation of TYMS and TK1, enzymes related to 5-FU
      resistance.

PMID- 23557933
TI  - One-year supplementation with a grape extract containing resveratrol modulates
      inflammatory-related microRNAs and cytokines expression in peripheral blood
      mononuclear cells of type 2 diabetes and hypertensive patients with coronary
      artery disease.
AB  - Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory
      effects but human trials evidencing these effects in vivo are limited.
      Furthermore, the molecular mechanisms triggered in humans following the oral
      intake of RES are not yet understood. Therefore, the purpose of this study was to
      investigate the molecular changes in peripheral blood mononuclear cells (PBMCs)
      associated to the one-year daily intake of a RES enriched (8 mg) grape extract
      (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We
      used microarrays and RT-PCR to analyze expression changes in genes and microRNAs
      (miRs) involved in the inflammatory response modulated by the consumption of GE
      RES in comparison to a placebo and GE lacking RES. We also examined the changes
      in several serobiochemical variables, inflammatory and fibrinolytic markers. Our
      results showed that supplementation with GE or GE-RES did not affect body weight,
      blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold
      standard medication in these patients. We did not find either any significant
      change on serum inflammatory markers except for a significant reduction of ALP
      and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1beta
      and TNF-alpha was significantly reduced and that of the transcriptional repressor
      LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a
      group of miRs involved in the regulation of the inflammatory response: miR-21,
      miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly
      correlated and altered in the group consuming the GE-RES for 12 months. Our
      results provide preliminary evidence that long-term supplementation with a grape
      extract containing RES downregulates the expression of key pro-inflammatory
      cytokines with the involvement of inflammation-related miRs in circulating immune
      cells of T2DM hypertensive medicated patients and support a beneficial
      immunomodulatory effect in these patients.

PMID- 23557934
TI  - A chronometric functional sub-network in the thalamo-cortical system regulates
      the flow of neural information necessary for conscious cognitive processes.
AB  - The thalamo-cortical system has been defined as a neural network associated with
      consciousness. While there seems to be wide agreement that the thalamo-cortical
      system directly intervenes in vigilance and arousal, a divergence of opinion
      persists regarding its intervention in the control of other cognitive processes
      necessary for consciousness. In the present manuscript, we provide a review of
      recent scientific findings on the thalamo-cortical system and its role in the
      control and regulation of the flow of neural information necessary for conscious
      cognitive processes. We suggest that the axis formed by the medial prefrontal
      cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus,
      and midline nucleus), represents a core component for consciousness. This axis
      regulates different cerebral structures which allow basic cognitive processes
      like attention, arousal and memory to emerge. In order to produce a synchronized
      coherent response, neural communication between cerebral structures must have
      exact timing (chronometry). Thus, a chronometric functional sub-network within
      the thalamo-cortical system keeps us in an optimal and continuous functional
      state, allowing high-order cognitive processes, essential to awareness and
      qualia, to take place.

PMID- 23557935
TI  - Morphological and functional deterioration of the rat thyroid following chronic
      exposure to low-dose PCB118.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can
      severely disrupt the synthesis and secretion of endocrine hormones. To
      investigate the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on thyroid
      structure and function, 40 male Wistar rats were divided into 4 equal treatment
      groups and administered vehicle or one of three doses of PCB118. The experimental
      groups received intraperitoneal (i.p.) injection of 10, 100, or 1000MUg/kg/day
      PCB118, 5 days per week for 13 weeks, whereas the control group was injected with
      corn oil (vehicle). Serum concentrations of free thyroxine (FT4), free
      triiodothyronine (FT3) and thyroid stimulating hormone (TSH) were measured by
      radioimmunoassays. Histopathological and ultrastructural changes in the thyroid
      were observed under light microscopy and transmission electron microscopy (TEM).
      The mRNA expression levels of the sodium-iodide symporter (NIS) and thyroglobulin
      (TG) were quantified by real-time PCR. Increasing doses of PCB118 resulted in
      progressively lower FT3, FT4 and TSH concentrations in serum. Injection of PCB118
      at all doses led to histopathological deterioration of the thyroid characterized
      by follicular hyperplasia and expansion, shedding of epithelial cells and
      fibrinoid necrosis. Follicle cells exhibited swollen or vacuolated endoplasmic
      reticula, as revealed by TEM. Exposure to PCB118 also caused significant
      decreases in NIS and TG mRNA expression levels. Chronic exposure to low-dose
      PCB118 and other PCB congeners may be a significant risk factor for thyroid
      diseases. 

PMID- 23557936
TI  - Canine keratinocytes upregulate type I interferons and proinflammatory cytokines
      in response to poly(dA:dT) but not to canine papillomavirus.
AB  - Papillomaviruses (PV) are double stranded (ds) DNA viruses that infect epithelial
      cells within the skin or mucosa, most often causing benign neoplasms that
      spontaneously regress. The immune system plays a key role in the defense against
      PVs. Since these viruses infect keratinocytes, we wanted to investigate the role
      of the keratinocyte in initiating an immune response to canine papillomavirus-2
      (CPV-2) in the dog. Keratinocytes express a variety of pattern recognition
      receptors (PRR) to distinguish different cutaneous pathogens and initiate an
      immune response. We examined the mRNA expression patterns for several recently
      described cytosolic nucleic acid sensing PRRs in canine monolayer keratinocyte
      cultures using quantitative reverse transcription-polymerase chain reaction.
      Unstimulated normal cells were found to express mRNA for melanoma differentiation
      associated gene 5 (MDA5), retinoic acid-inducible gene I (RIG-I), DNA-dependent
      activation of interferon regulatory factors, leucine rich repeat flightless
      interacting protein 1, and interferon inducible gene 16 (IFI16), as well as their
      adaptor molecules myeloid differentiation primary response gene 88, interferon
      beta promoter stimulator 1, and endoplasmic reticulum-resident transmembrane
      protein stimulator of interferon genes. When stimulated with synthetic dsDNA
      [poly(dA:dT)] or dsRNA [poly(I:C)], keratinocytes responded with increased mRNA
      expression levels for interleukin-6, tumor necrosis factor-alpha, interferon
      beta, RIG-I, IFI16, and MDA5. There was no detectable increase in mRNA
      expression, however, in keratinocytes infected with CPV-2. Furthermore, CPV-2
      infected keratinocytes stimulated with poly(dA:dT) and poly(I:C) showed similar
      mRNA expression levels for these gene products when compared with expression
      levels in uninfected cells. These results suggest that although canine
      keratinocytes contain functional PRRs that can recognize and respond to dsDNA and
      dsRNA ligands, they do not appear to recognize or initiate a similar response to
      CPV-2.

PMID- 23557937
TI  - Fracture of the body of hamate associated with a fracture of the base of fourth
      metacarpal: A case report and review of literature of the last 20 years.
AB  - INTRODUCTION: Fractures of the carpal bones are often difficult to diagnose and
      treat due to the complex bone architecture of this region. Hamate fractures,
      particularly body fractures, are extremely uncommon. PRESENTATION OF CASE: We
      present a case of a coronal fracture of the hamate associated with a fracture of
      the base of the fourth metacarpal, which was treated by open reduction and
      internal fixation. DISCUSSION: Some of hamate body fractures are associated with
      other injuries like metacarpal fractures. Its diagnosis is difficult and requires
      a high clinical suspicion and a proper radiological examination. This fracture is
      a very rare lesion that can raise questions about their most adequate diagnostic
      and therapeutic approaches. CONCLUSION: After reviewing the literature, we
      conclude that there is a high rate of delay in the diagnosis of these lesions,
      probably due to their rarity and to the lack of radiological studies specifically
      targeting this region. Despite this, surgical treatment in its different
      modalities has been shown to have the best clinical and functional results.

PMID- 23557938
TI  - Surgical treatment of primary aortojejunal fistula.
AB  - INTRODUCTION: Primary aortoenteric fistula is a rare clinical situation with a
      high mortality rate. One should suspect that condition when an abdominal aortic
      aneurysm is known to be present. We describe the case of a 60 year old man who
      presented with upper gastrointestinal bleeding as the first and sole
      manifestation of an abdominal aortic aneurysm, due to the rupture of the aneurysm
      in the jejunum. PRESENTATION OF CASE: The patient was admitted with hematemesis
      and melena. He reported no abdominal pain. Upper gastrointestinal endoscopy
      disclosed no bleeding or lesions of the stomach and duodenum. Bleeding stopped
      the following day, only to recur 4 days later. The patient was then subjected to
      abdominal CT scan, which revealed the presence of a subrenal aortic aneurysm,
      with fistulization to the small intestine. At laparotomy the aortic aneurysm was
      adherent to the first centimeters of jejunum. The diseased aorta was excised and
      replaced with a Dacron Y graft in situ. DISCUSSION: Primary aortojejunal fistulas
      are only rarely encountered. They usually are the result of a nonspecific
      aneurysm of the abdominal aorta. They usually manifest with premonitory bleeding,
      followed by catastrophic hemorrhage few days later. Even with surgery the
      mortality rate is high. CONCLUSION: Diagnosis of primary aortoenteric fistula
      requires a high index of suspicion in cases of upper gastrointestinal bleeding,
      especially when endoscopy is negative and there is no knowledge of the existence
      of an abdominal aortic aneurysm. CT scan and prompt surgery are crucial to the
      survival of these patients.

PMID- 23557939
TI  - Navigating neurites utilize cellular topography of Schwann cell somas and
      processes for optimal guidance.
AB  - The path created by aligned Schwann cells (SCs) after nerve injury underlies
      peripheral nerve regeneration. We developed geometric bioinspired substrates to
      extract key information needed for axon guidance by deconstructing the
      topographical cues presented by SCs. We have previously reported materials that
      directly replicate SC topography with micro- and nanoscale resolution, but a
      detailed explanation of the means of directed axon extension on SC topography has
      not yet been described. Here, using neurite tracing and time-lapse microscopy, we
      analyzed the SC features that influence axon guidance. Novel
      poly(dimethylsiloxane) materials, fabricated via photolithography, incorporated
      bioinspired topographical components with the shapes and sizes of aligned SCs,
      namely somas and processes, where the lengths of the processes were varied but
      the soma geometry and dimensions were kept constant. Rat dorsal root ganglia
      neurites aligned to all materials presenting bioinspired topography after 5days
      in culture and aligned to bioinspired materials presenting soma and process
      features after only 17h in culture. The key findings of this study were: neurite
      response to underlying bioinspired topographical features was time dependent,
      with neurites aligned most strongly to materials presenting combinations of soma
      and process features at 5days, with higher than average density of either process
      or soma features, but at 17h they aligned more strongly to materials presenting
      average densities of soma and process features and to materials presenting
      process features only. These studies elucidate the influence of SC topography on
      axon guidance in a time-dependent setting and have implications for the
      optimization of nerve regeneration strategies.

PMID- 23557941
TI  - Joint efforts needed to stop transmission of tuberculosis in Europe.

PMID- 23557940
TI  - The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion
      during the follicular phase of the estrous cycle in ewes.
AB  - This study was designed to determine the effect of a potent subcutaneously
      injected acetylcholinesterase inhibitor, rivastigmine (6mg/animal), on the
      gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during
      inflammation induced by an intravenous lipopolysaccharide (LPS) (400ng/kg)
      injection in ewes during the follicular phase of the estrous cycle. The results
      are expressed as the mean values from -2 to -0.5h before and +1 to +3h after
      treatment. Rivastigmine decreased the acetylcholinesterase concentration in the
      blood plasma from 176.9+/-9.5 to 99.3+/-15.1MUmol/min/ml. Endotoxin suppressed LH
      (5.4+/-0.6ng/ml) and GnRH (4.6+/-0.4pg/ml) release; however, the rivastigmine
      injection restored the LH concentration (7.8+/-0.8ng/ml) to the control value
      (7.8+/-0.7ng/ml) and stimulated GnRH release (7.6+/-0.8pg/ml) compared to the
      control (5.9+/-0.4pg/ml). Immune stress decreased expression of the GnRH gene and
      its receptor (GnRH-R) in the median eminence as well as LHbeta and GnRH-R in the
      pituitary. In the case of the GnRH and LHbeta genes, the suppressive effect of
      inflammation was negated by rivastigmine. LPS stimulated cortisol and prolactin
      release (71.1+/-14.7 and 217.1+/-8.0ng/ml) compared to the control group (9.0+/
      5.4 and 21.3+/-3.5ng/ml). Rivastigmine also showed a moderating effect on
      cortisol and prolactin secretion (43.1+/-13.1 and 169.7+/-29.5ng/ml). The present
      study shows that LPS-induced decreases in GnRH and LH can be reduced by the AChE
      inhibitor. This action of the AChE inhibitor could result from the suppression of
      pro-inflammatory cytokine release and the attenuation of the stress response.
      However, a direct stimulatory effect of ACh on GnRH/LH secretion should also be
      considered.

PMID- 23557943
TI  - Extrapulmonary tuberculosis in the European Union and European Economic Area,
      2002 to 2011.
AB  - Tuberculosis (TB) is decreasing in the European Union/European Economic Area
      (EU/EEA), but remains a significant public health problem. Although pulmonary TB
      accounts for the majority of the cases and is the main transmissible form of the
      disease, extrapulmonary TB also contributes to the burden of disease and does not
      receive specific attention in international control strategies. We performed a
      descriptive analysis to assess the burden and trends of extrapulmonary TB in
      EU/EEA countries. During 2002-11, 167,652 cases of extrapulmonary TB were
      reported by the 30 Member States. Extrapulmonary TB accounted for 19.3% of all
      notified cases, ranging from 5.8% to 44.4% among the Member States. Overall, TB
      notification rates decreased in 2002-11 due to a decrease in pulmonary TB.
      Notification rates of extrapulmonary TB remained stable at 3.4 per 100,000 in
      2002 and 3.2 per 100,000 in 2011. Thus the proportion of extrapulmonary TB
      increased from 16.4% in 2002 to 22.4% in 2011. Of all extrapulmonary TB cases
      reported during 2002-11, 37.9% were foreign-born or citizens of another country,
      33.7% were culture-confirmed, and the overall treatment success was 81.4%. A
      significant percentage of notified TB cases are extrapulmonary, and in contrast
      to pulmonary TB, extrapulmonary TB rates are not decreasing.

PMID- 23557942
TI  - Fatal case of extensively drug-resistant Mycobacterium tuberculosis Beijing
      genotype infection in an injecting drug user, Athens, Greece, 2012.
AB  - We present the first fatal case of extensively drug-resistant tuberculosis (XDR
      TB) in an injecting drug user (IDU) in Athens, Greece, co-infected with human
      immunodeficiency virus and hepatitis C virus and discuss the implications for
      public health. Despite immediate initiation of treatment, the patient's condition
      gradually deteriorated and he died 16 days after hospital admission because of
      multiple organ failure. The contact tracing investigation revealed no further
      infections among the patient's contacts.

PMID- 23557944
TI  - The burden of extrapulmonary and meningitis tuberculosis: an investigation of
      national surveillance data, Germany, 2002 to 2009.
AB  - Tuberculosis (TB) surveillance commonly focuses on pulmonary (PTB) where the main
      organ affected is the lung. This might lead to underestimate extrapulmonary TB
      (EPTB) forms, where in addition to the lung other sites are affected by TB. In
      Germany, TB notification data provide the main site and the secondary site of
      disease. To gain an overview of all the different EPTB forms, we analysed German
      TB notification data between 2002 and 2009 using information on both main and
      secondary disease site to describe all individual EPTB forms. Further, we
      assessed factors associated with meningitis using multivariable logistic
      regression. Solely analysing the main site of disease, lead to one third of EPTB
      manifestations being overlooked. Case characteristics varied substantially across
      individual extrapulmonary forms. Of 46,349 TB patients, 422 (0.9%) had meningitis
      as main or secondary site. Of those, 105 (25%) of the 415 with available
      information had died. Multivariable analysis showed that meningitis was more
      likely in children younger than five years and between five and nine years-old
      (odds ratio (OR): 4.90; 95% confidence interval (CI): 3.40-7.07 and OR: 2.65; 95%
      CI: 1.40-5.00), in females (OR: 1.42; 95% CI: 1.17-1.73), and in those born in
      the World Health Organization (WHO) regions of south-east Asia (OR: 2.38; 95% CI:
      1.66-3.43) and eastern Mediterranean (OR: 1.51; 95% CI: 1.02-2.23). Overall, EPTB
      manifestations, including meningitis, which is often fatal, were underestimated
      by routine analysis. We thus recommend using all information on disease
      manifestation generated by surveillance to monitor severe forms and to transfer
      the gained knowledge to TB case management where awareness of EPTB is most
      important.

PMID- 23557945
TI  - Treatment outcome monitoring of pulmonary tuberculosis cases notified in France
      in 2009.
AB  - The proportion of patients considered to be cured is a key indicator to assess
      national tuberculosis (TB) control. In France, TB treatment outcome monitoring
      was implemented in 2007. This article presents national results on treatment
      outcome among patients with pulmonary TB reported in France in 2009 and explores
      determinants of potentially unfavourable outcome. Information on treatment
      outcome was reported for 63% of eligible pulmonary cases of whom 70% had a
      successful outcome. In a multivariate analysis, potentially unfavourable outcome
      (17%), compared to treatment success, was significantly associated with being
      male, born abroad and having lived in France for less than 10 years, being in
      congregate settings when treatment was initiated, or having a previous history of
      anti-TB treatment. Enhanced awareness of treatment outcome monitoring is
      essential to improve the coverage and the quality of information. Earlier
      diagnosis and improved management of the disease in the elderly may reduce death
      due to TB. The high proportion of potentially unfavourable outcomes should be
      further investigated as they may require additional vigilance and/or actions in
      term of efforts of TB control in some population groups.

PMID- 23557946
TI  - Challenges in diagnosing extrapulmonary tuberculosis in the European Union, 2011.
AB  - In the European Union (EU) 72,334 tuberculosis (TB) cases were notified in 2011,
      of which 16,116 (22%) had extrapulmonary tuberculosis (EPTB). The percentage of
      TB cases with EPTB ranged from 4% to 48% in the reporting countries. This
      difference might be explained by differences in risk factors for EPTB or
      challenges in diagnosis. To assess the practices in diagnosis of EPTB we asked
      European Union/European Economic Area (EU/EEA) countries to participate in a
      report describing the diagnostic procedures and challenges in diagnosing EPTB.
      Eleven EU Member States participated and reports showed that in the majority EPTB
      is diagnosed by a pulmonologist, sometimes in collaboration with the doctor who
      is specialised in the organ where the symptoms presented. In most countries a
      medical history and examination is followed by invasive procedures, puncture or
      biopsy, to collect material for confirmation of the disease (by
      culture/histology/cytology). Some countries also use the tuberculin skin test or
      an interferon-gamma-release-assay. A wide variety of radiological tests may be
      used. Countries that reported challenges in the diagnosis of EPTB reported that
      EPTB is often not considered because it is a rare disease and most medical
      professionals will not have experience in diagnosing EPTB. The fact that EPTB can
      present with a variety of symptoms that may mimic symptoms of other pathologies
      does pose a further challenge in diagnosis. In addition, obtaining an appropriate
      sample for confirmation of EPTB was frequently mentioned as a challenge. In
      summary, diagnosis of EPTB poses challenges due to the diversity of symptoms with
      which EPTB may present, the low level of suspicion of clinicians, and due to the
      difficulty in obtaining an adequate sample for confirmation.

PMID- 23557947
TI  - Tuberculosis diagnostic delay and therapy outcomes of non-national migrants in
      Tel Aviv, 1998-2008.
AB  - Non-national migrants have limited access to medical therapy. This study compares
      diagnostic delay and treatment outcomes of non-insured non-national migrants
      (NINNM) with insured Israeli citizens (IC) in the Tel Aviv tuberculosis (TB)
      clinic between 1998 and 2008. Patient delay was the time from symptoms onset to
      doctor's visit, while system delay was measured from doctor visit to anti-TB
      therapy administration. We randomly sampled 222 NINNM and 265 IC. NINNM were
      younger than IC, had lower male to female ratio and fewer smoked. They had less
      drug/alcohol abuse, more cavitations on chest radiography, longer patient and
      shorter system delay. Mean patient and system delays of all patients were 25 +/-
      14 and 79 +/- 42 days, respectively. In multivariate analysis, being NINNM,
      asymptomatic or smoking predicted longer patient delay, while being asymptomatic
      or having additional co-morbidity predicted longer system delay. Treatment
      success in sputum smear-positive pulmonary TB NINNM was 81% and 95.7% in IC
      (p=0.01). Treatment success was not associated with patient or system delay. In
      multivariate analysis, work security and treatment adherence predicted treatment
      success. NINNM had longer patient delay and worse therapy outcome, while IC had
      longer system delay. Both delays should be reduced. NINNM should be informed that
      TB therapy is free and unlinked with deportation.

PMID- 23557948
TI  - ECDC and WHO/Europe joint report on tuberculosis surveillance and monitoring in
      Europe.

PMID- 23557950
TI  - The elixir of insatiable curiosity.

PMID- 23557951
TI  - Autoantigenicity of carbonic anhydrase 1 in patients with abdominal aortic
      aneurysm, revealed by proteomic surveillance.
AB  - Abdominal aortic aneurysm (AAA) is sometimes detected in patients with
      atherosclerosis. One of the histological characteristics of AAA walls is
      infiltration of inflammatory cells, in which autoimmunity may be involved.
      Thereby, we here surveyed autoantigens in AAA walls by proteomics. Specifically,
      we separated proteins extracted from AAA wall samples by 2-dimensional
      electrophoresis and detected candidate autoantigens by western blotting. One of
      the detected candidates was carbonic anhydrase 1 (CA1). ELISA confirmed that the
      autoantibodies to CA1 were detected more frequently in AAA patients (n=13) than
      in healthy donors (n=25) (p=0.03). Interestingly, some serum samples from the AAA
      patients reacted to CA1 of the AAA walls stronger than to CA1 of peripheral blood
      mononuclear cells from healthy donors. Our data indicate that CA1 in the AAA
      walls would be modified to express neo-epitope(s) and that the autoimmunity to
      CA1 may be involved in the pathogenesis of AAA.

PMID- 23557953
TI  - Best evidence: comments on meta-analysis of coiling versus clipping.

PMID- 23557952
TI  - Perivascular spaces are associated with atherosclerosis: an insight from the
      Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: Perivascular spaces are potential spaces found between
      brain blood vessels and surrounding leptomeninges that have been associated with
      cardiovascular risk factors and dementia, but less is known about their
      relationship to atherosclerosis. We tested the hypothesis that perivascular
      spaces are associated with atherosclerosis. MATERIALS AND METHODS: Participants
      from the Northern Manhattan Study who remained stroke-free were invited to
      participate in an MR imaging substudy. Parenchymal hypointensities of <3 mm
      identified on brain axial T1-weighted MR imaging were scored as perivascular
      spaces. A semiquantitative score was created to express the degree of brain
      involvement. Generalized linear models were used to assess statistical
      associations with carotid plaque as a surrogate marker of atherosclerosis.
      RESULTS: The studied sample included 706 participants (mean age, 72.6 +/- 8.0
      years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57%
      with high cholesterol). The perivascular spaces score ranged from 0 to 19 with
      52% of the sample having a perivascular spaces score of <=4. In unadjusted
      analysis, perivascular spaces were associated with age (beta = 0.01 per year, P =
      < .001), non-Hispanic black race-ethnicity (beta = 0.16, P = .02), hypertension
      (beta = 0.24, P = < .001), and carotid plaque (beta = 0.22, P < .001). In
      multivariable analysis, only age (beta = 0.01, P = .02), hypertension (beta =
      0.17, P = .01), and carotid plaque (beta = 0.22, P = < .001) remained
      independently associated with perivascular spaces. CONCLUSIONS: Perivascular
      spaces were more frequently found in older participants, in those with
      hypertension, and in the presence of carotid plaque. These results suggest that
      mechanisms leading to atherosclerosis might also lead to an increased number of
      perivascular spaces. These results need confirmation in prospective studies.

PMID- 23557954
TI  - From hard drives to flash drives to DNA drives.

PMID- 23557955
TI  - Endovascular treatment of deep hemorrhagic brain arteriovenous malformations with
      transvenous onyx embolization.
AB  - SUMMARY: Brain AVMs are a rare cause of cerebral hemorrhage and SAH, and their
      treatment is still debated. The aim of this study was to describe a novel
      endovascular approach with transvenous embolization of deep hemorrhagic brain
      AVMs. Five patients (3 females, 2 males; mean age, 33.2 years) underwent a
      transvenous embolization of a deep hemorrhagic brain AVM at our institution
      between February and April 2012. Clinical and angiographic data at the end of the
      procedure and after 6 months are reported. All the AVMs were completely
      obliterated, and no intra- or postprocedural complications occurred. The clinical
      outcome was unchanged or improved in all patients. Transvenous endovascular
      treatment may be considered in small, hemorrhagic, and deep AVMs with single deep
      drainage in those cases in which neurosurgical and radiosurgical treatment might
      not be indicated.

PMID- 23557956
TI  - Retrospective review of rapid pediatric brain MR imaging at an academic
      institution including practice trends and factors affecting scan times.
AB  - BACKGROUND AND PURPOSE: In an effort to reduce radiation exposure in children
      requiring regular follow up for shunted hydrocephalus, our institution
      implemented a rapid brain MR imaging protocol. The purpose of this study was to
      review an academic practice experience with pediatric rapid brain MR imaging
      without patient sedation in the evaluation of hydrocephalus and a limited group
      of other conditions. MATERIALS AND METHODS: We retrospectively analyzed limited
      sequence, rapid brain MR imaging scans performed in nonsedated patients younger
      than 14 years between April 2009 and December 2011. So-called failed examinations
      were determined by consensus of 2 authors as insufficiently diagnostic for
      evaluation of ventricular size. CT and MR imaging quarterly volumes for
      hydrocephalus-related indications were determined from 2005-2012. Multivariable
      logistic regression analysis was performed to elucidate factors potentially
      affecting scan durations including examination indication and patient age, sex,
      inpatient status, and clinical conditions. RESULTS: A total of 398 examinations
      were performed on 168 patients (103 boys, 65 girls; median age, 13 months). None
      were deemed to be failed examinations. Median scan duration was 4.43 minutes
      (interquartile range, 4.42 minutes-5.88 minutes; SD, 2.42 minutes). Examination
      indication of altered mental status was the only factor associated with increased
      scan duration (+1.77 minutes; P = .0021). Hydrocephalus-related imaging volumes
      approximately doubled in the 7 years reviewed, but rapid MR imaging introduced in
      2009 is quickly replacing CT scanning for these indications, accounting for
      nearly 7 of every 8 examinations at the end of the study period. CONCLUSIONS: In
      every case of initial work-up and follow-up, rapid brain MR imaging effectively
      evaluated ventricular size and/or intracranial fluid and represents a viable
      alternative to CT scanning, irrespective of a child's age or clinical condition.
      For this indication and patient group, MR imaging is now the predominant imaging
      method in our practice.

PMID- 23557957
TI  - Incidental thyroid nodules on CT: evaluation of 2 risk-categorization methods for
      work-up of nodules.
AB  - BACKGROUND AND PURPOSE: Thyroid nodules are common incidental findings on CT, but
      there are no clear guidelines regarding their further diagnostic work-up. This
      study compares the performance of 2 risk-categorization methods of selecting CT
      detected incidental thyroid nodules for work-up. MATERIALS AND METHODS: The 2
      categorization methods were method A, based on nodule size >=10 mm, and method B,
      a 3-tiered system based on aggressive imaging features, patient age younger than
      35 years or nodule size of >=15 mm. In part 1, the 2 categorization methods were
      applied to thyroid cancers in the SEER data base of the National Cancer Institute
      to compare the cancer capture rates and survival. In part two, 755 CT neck scans
      at our institution were retrospectively reviewed for the presence of ITNs of >=5
      mm, and the same 2 categorization methods were applied to the CT cases to compare
      the number of patients who would theoretically meet the criteria for work-up.
      Comparisons of proportions of subjects captured under methods A and B were made
      by using the McNemar test. RESULTS: For 84,720 subjects in the SEER data base,
      methods A and B each captured 74% (62,708/84,720 and 62,586/84,720, respectively)
      of malignancies. SEER subjects who would not have met the criteria for further
      work-up by both methods had equally excellent 10-year cause-specific and relative
      survival of >99%. For part 2, the prevalence of ITNs of >=5 mm at our institution
      was 133/755 (18%). The number of ITNs that would be recommended for work-up by
      method A was 57/133 (43%) compared with 31/133 (23%) for method B (P < .0005).
      CONCLUSIONS: Compared with using a 10-mm cutoff, the 3-tiered risk-stratification
      method identified fewer ITNs for work-up but captured the same proportion of
      cancers in a national data base and showed no difference in missing high
      mortality cancers.

PMID- 23557958
TI  - Illustrated review of the embryology and development of the facial region, part
      3: an overview of the molecular interactions responsible for facial development.
AB  - SUMMARY: Parts 1 and 2 of this review discussed the complex morphogenesis of the
      face. However, the molecular processes that drive the morphology of the face were
      not addressed. Part 3 of this review will present an overview of the genes and
      their products that have been implicated in the developing face.

PMID- 23557959
TI  - Inherited forms of Creutzfeldt-Jakob disease.

PMID- 23557961
TI  - Trichoblastoma shares cytokeratin 15-positive cells with seborrheic keratosis in
      a composite tumor--novel immunohistochemical findings.

PMID- 23557960
TI  - Effects of increased image noise on image quality and quantitative interpretation
      in brain CT perfusion.
AB  - BACKGROUND AND PURPOSE: There is a desire within many institutions to reduce the
      radiation dose in CTP examinations. The purpose of this study was to simulate
      dose reduction through the addition of noise in brain CT perfusion examinations
      and to determine the subsequent effects on quality and quantitative
      interpretation. MATERIALS AND METHODS: A total of 22 consecutive reference CTP
      scans were identified from an institutional review board-approved prospective
      clinical trial, all performed at 80 keV and 190 mAs. Lower-dose scans at 188,
      177, 167, 127, and 44 mAs were generated through the addition of spatially
      correlated noise to the reference scans. A standard software package was used to
      generate CBF, CBV, and MTT maps. Six blinded radiologists determined quality
      scores of simulated scans on a Likert scale. Quantitative differences were
      calculated. RESULTS: For qualitative analysis, the correlation coefficients for
      CBF (-0.34; P < .0001), CBV (-0.35; P < .0001), and MTT (-0.44; P < .0001) were
      statistically significant. Interobserver agreements in quality for the simulated
      188-, 177-, 167-, 127-, and 44-mAs scans for CBF were 0.95, 0.98, 0.98, 0.95, and
      0.52, respectively. Interobserver agreements in quality for the simulated CBV
      were 1, 1, 1, 1, and 0.83, respectively. For MTT, the interobserver agreements
      were 0.83, 0.86, 0.88, 0.74, and 0.05, respectively. For quantitative analysis,
      only the lowest simulated dose of 44 mAs showed statistically significant
      differences from the reference scan values for CBF (-1.8; P = .04), CBV (0.07; P
      < .0001), and MTT (0.46; P < .0001). CONCLUSIONS: From a reference CTP study
      performed at 80 keV and 190 mAs, this simulation study demonstrates the potential
      of a 33% reduction in tube current and dose while maintaining image quality and
      quantitative interpretations. This work can be used to inform future studies by
      using true, nonsimulated scans.

PMID- 23557962
TI  - Determination of the genetic similarities of fingerprints from Escherichia coli
      O157:H7 isolated from different sources in the North West Province, South Africa
      using ISR, BOXAIR and REP-PCR analysis.
AB  - The aim of this study was to determine the genetic relationships of Escherichia
      coli O157:H7 isolated from pigs, cattle, pork, beef, humans and water samples
      using REP, ISR and BOXAIR PCR analysis. A total of 94 isolates were subjected to
      the REP-PCR analysis while 95 were screened for ISR and BOXAIR PCR fingerprints.
      The band sizes for amplicons from the ISR-PCR analysis ranged from 0.173kb to
      0.878kb. However, a large proportion of the isolates had four bands ranging from
      0.447kb to 0.878kb. Cluster analysis of the BOXAIR PCR profiles based on banding
      patterns revealed seven main clusters. It was identified in the clusters III, IV
      and VII in the BOXAIR PCR that 17.9%, 16.8% and 18.9%, of E. coli O157:H7
      isolates respectively were present from all the animal species, meat and water
      samples. REP-PCR analysis produced 9 different patterns with bands ranging from 0
      to 12 per isolate. The band sizes ranged from 200bp to 8000bp. Nine major
      clusters (I-IX) were identified. From the three different species sampled cluster
      eight was the largest and a mixed cluster with 23.4% (22/94) of the E. coli
      O157:H7 isolates. These indicate that food products obtained from supermarkets in
      the study area are contaminated with E. coli O157:H7.

PMID- 23557964
TI  - Fused in sarcoma (FUS): an oncogene goes awry in neurodegeneration.
AB  - Fused in sarcoma (FUS) is a nuclear DNA/RNA binding protein that regulates
      different steps of gene expression, including transcription, splicing and mRNA
      transport. FUS has been implicated in neurodegeneration, since mutations in FUS
      cause familial amyotrophic lateral sclerosis (ALS-FUS) and lead to the cytosolic
      deposition of FUS in the brain and spinal cord of ALS-FUS patients. Moreover, FUS
      and two related proteins of the same protein family (FET family) are co-deposited
      in cytoplasmic inclusions in a subset of patients with frontotemporal lobar
      degeneration (FTLD-FUS). Cytosolic deposition of these otherwise nuclear proteins
      most likely causes the loss of a yet unknown essential nuclear function and/or
      the gain of a toxic function in the cytosol. Here we summarize what is known
      about the physiological functions of the FET proteins in the nucleus and
      cytoplasm and review the distinctive pathomechanisms that lead to the deposition
      of only FUS in ALS-FUS, but all three FET proteins in FTLD-FUS. We suggest that
      ALS-FUS is caused by a selective dysfunction of FUS, while FTLD-FUS may be caused
      by a dysfunction of the entire FET family. This article is part of a Special
      Issue entitled 'RNA and splicing regulation in neurodegeneration'. 

PMID- 23557963
TI  - Molecular targeting of Galpha and Gbetagamma subunits: a potential approach for
      cancer therapeutics.
AB  - G-Protein-coupled receptors (GPCRs) signal through G protein alpha and betagamma
      subunit families to regulate a wide range of physiological and pathophysiological
      processes. As such, GPCRs are major targets for therapeutic drugs. Downstream
      targets of GPCRs have also gained interest as a therapeutic approach to complex
      pathologies involving multiple GPCRs. One such approach involves targeting of the
      G proteins themselves. Several small molecule Galpha and Gbetagamma modulators
      have been developed and been tested in various animal models of disease. Here we
      will discuss the requirements for targeting Galpha and Gbetagamma subunits, the
      mechanisms of action of currently identified inhibitors, and focus on the
      potential utility of Galpha and Gbetagamma inhibitors in the treatment of various
      cancers.

PMID- 23557965
TI  - Metformin downregulates Th17 cells differentiation and attenuates murine
      autoimmune arthritis.
AB  - INTRODUCTION: This study was undertaken to determine whether metformin has anti
      inflammatory effects in the collagen antibody-induced arthritis (CAIA) murine
      model. The effect of metformin on Th17 cell differentiation was also
      investigated. METHODS: CAIA mice were treated with 100 and 150 mg/kg i.p.
      metformin (low- and high-dose groups, respectively). Arthritis activity and
      histological joint destruction were studied. Flow cytometry was used to (i)
      determine RORgammat-expressing CD4+ percentages in draining axillary lymph nodes
      (ALNs) from metformin-treated and untreated mice with CAIA, (ii) determine Th17
      percentages in splenic CD4+ T cells cultured ex vivo for 3 days in Th17
      differentiation-inducing conditions, and (iii) determine the percentages of
      RORgammat+CD4+ T cells when normal splenic T cells from DBA/1 mice were cultured
      in Th17-differentiation-inducing conditions together with various metformin
      doses. Western blot analysis was used to assess the intracellular signaling of
      the metformin-treated splenocytes. RESULTS: Metformin attenuated both arthritis
      scores and bone destruction in CAIA mice, decreased the serum levels of the pro
      inflammatory cytokines, TNF-alpha and IL-1, and reduced the number of
      RORgammat+CD4+ T cells in the ALNs. Splenocytes from metformin-treated CAIA mice
      differentiated less readily into Th17 cells upon ex vivo stimulation. Metformin
      treatment of normal cells cultured in Th17-differentiation-inducing conditions
      decreased the number of RORgammat-expressing CD4+ cells in a dose-dependent
      manner and downregulated STAT3 phosphorylation via the AMPK pathway. CONCLUSIONS:
      Metformin had an anti-inflammatory effect on murine autoimmune arthritis due to
      the inhibition of Th17 cell differentiation. Metformin may have a possible
      therapeutic value for treatment of rheumatoid arthritis.

PMID- 23557966
TI  - Ucf-101 protects against cerebral oxidative injury and cognitive impairment in
      septic rat.
AB  - BACKGROUND: Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in
      caspase-dependent and caspase-independent cell apoptosis. It has been verified
      that Omi/HtrA2 is related to apoptosis due to oxidative stress, which may play an
      important role in the integrity of mitochondria. Ucf-101 is a specific inhibitor
      of Omi/HtrA2 and it has been demonstrated that Ucf-101 has organ protective
      effects in a variety of in vitro and in vivo studies. The aim of our study was to
      examine the neuroprotective effects of Ucf-101 on cerebral oxidative injury and
      cognitive impairment in septic rats. METHODS: Male Sprague Dawley rats are
      subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy. Rats
      were divided into 4 groups: (1) a sham group plus normal saline (10 mL/kg); (2) a
      sham group plus Ucf-101 (10 umol/kg); (3) CLP plus normal saline (10 mL/kg); and
      (4) CLP plus Ucf-101 (10 umol/kg). Brain tumor necrosis factor (TNF)-alpha level,
      caspase-3 and caspase-9 activities, malondialdehyde (MDA) content and catalase
      (CAT) activities were examined. TUNEL staining was utilized to evaluate the
      amount of apoptosis and the cognitive function was evaluated by the MWM test. The
      study also assessed the clinical scores of animals and the survival time for the
      7-day period. RESULTS: CLP resulted in a poor survival rate, evidence of
      hippocampal oxidative injury, cell apoptosis and cognitive dysfunction as well as
      elevated TNF-alpha level and caspases activities, increased weight loss and
      clinical scores. Ucf-101 pre-treatment could significantly inhibit caspases
      activities and cell apoptosis, reduce TNF-alpha and MDA levels, slightly reverse
      CAT activities in the brain and attenuate this CLP effect on cognitive
      dysfunction. In addition, the survival rate and survival time was significantly
      improved by pre-treatment with Ucf-101. CONCLUSIONS: The present results
      demonstrated that ucf-101 has the neuroprotective effects on cerebral oxidative
      injury and cognitive impairment in septic rats.

PMID- 23557967
TI  - "AbroGATAed" human NK cell development.

PMID- 23557968
TI  - T cells in CLL: lost in migration.

PMID- 23557969
TI  - CD30, another useful predictor of survival in DLBCL?

PMID- 23557970
TI  - von Willebrand factor in its native environment.

PMID- 23557971
TI  - Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice
      leads to particle retention and gene expression changes in the absence of
      inflammation.
AB  - We investigated gene expression, protein synthesis, and particle retention in
      mouse lungs following intratracheal instillation of varying doses of nano-sized
      titanium dioxide (nano-TiO2). Female C57BL/6 mice were exposed to rutile nano
      TiO2 via single intratracheal instillations of 18, 54, and 162MUg/mouse. Mice
      were sampled 1, 3, and 28days post-exposure. The deposition of nano-TiO2 in the
      lungs was assessed using nanoscale hyperspectral microscopy. Biological responses
      in the pulmonary system were analyzed using DNA microarrays, pathway-specific
      real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA.
      Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs
      up to 28days post-instillation. DNA microarray analysis revealed approximately
      3000 genes that were altered across all treatment groups (+/-1.3 fold; p<0.1).
      Several inflammatory mediators changed in a dose- and time-dependent manner at
      both the mRNA and protein level. Although no influx of neutrophils was detected
      at the low dose, changes in the expression of several genes and proteins
      associated with inflammation were observed. Resolving inflammation at the medium
      dose, and lack of neutrophil influx in the lung fluid at the low dose, were
      associated with down-regulation of genes involved in ion homeostasis and muscle
      regulation. Our gene expression results imply that retention of nano-TiO2 in the
      absence of inflammation over time may potentially perturb calcium and ion
      homeostasis, and affect smooth muscle activities.

PMID- 23557972
TI  - Anthrax among heroin users in Europe possibly caused by same Bacillus anthracis
      strain since 2000.
AB  - Injection anthrax was described first in 2000 in a heroin-injecting drug user in
      Norway. New anthrax cases among heroin consumers were detected in the United
      Kingdom (52 cases) and Germany (3 cases) in 2009-10. In June 2012, a fatal case
      occurred in Regensburg, Bavaria. As of December 2012, 13 cases had been reported
      in this new outbreak from Germany, Denmark, France and the United Kingdom. We
      analysed isolates from 2009-10 and 2012 as well as from the first injection
      anthrax case in Norway in 2000 by comparative molecular typing using a high
      resolution 31 marker multilocus variable-number tandem repeat analysis (MLVA) and
      a broad single nucleotide polymorphism (SNP) analysis. Our results show that all
      cases may be traced back to the same outbreak strain. They also indicate the
      probability of a single source contaminating heroin and that the outbreak could
      have lasted for at least a decade. However, an additional serological pilot study
      in two German regions conducted in 2011 failed to discover additional anthrax
      cases among 288 heroin users.

PMID- 23557973
TI  - Barebacking among men who have sex with men recruited through a Swedish website:
      associations with sexual activities at last sexual encounter.
AB  - The research topic of barebacking emerged in the mid-1990s. Since then, a
      multitude of studies, largely from the United States, have produced invaluable
      knowledge of factors that help explain the behaviour among men who have sex with
      men (MSM), and that may contribute to HIV risk reduction programming and advice
      to counsellors working with barebackers. Given the scant empirical research about
      barebacking among European MSM, we conducted a survey among 3,634 MSM recruited
      through a web community in Nordic countries. The objectives of the study were
      twofold: to describe the sexual activities associated with barebacking behaviour
      at last sexual encounter, and to evaluate the relationship of barebacking with
      relevant variables. Men who reported barebacking (n=356) and men who did not
      (n=3,278) were compared. On the basis of the results of the analyses, the socio
      sexual profile of barebackers drawn was one that is at increased risk of
      acquiring human immunodeficiency virus (HIV) and other sexually transmitted
      infections due to their sexual practices, particularly unprotected anal
      intercourse, but also group sex and rimming. In a multivariate logistic
      regression analysis, the likelihood of engaging in barebacking was higher for MSM
      who reported more frequent HIV testing (odds ratio (OR)=5.16), a higher number of
      female sex partners (OR=16.80), using gay cruising places (OR=1.51) and gay chat
      rooms (OR=2.11).

PMID- 23557976
TI  - Oral health and oral quality of life in inactive patients with familial
      Mediterranean fever without amyloidosis.
AB  - OBJECTIVES: The aim of this study was to investigate oral and general health
      related quality of life (QoL) in patients with familial Mediterranean fever (FMF)
      disease. METHODS: In this cross-sectional study, 45 patients with FMF, 50 age-
      and sex-matched healthy controls (HC), and 50 patients with Behcet's disease (BD)
      as the disease control group were included. FMF disease activity was evaluated by
      using the FMF-severity score, as well as with erythrocyte sedimentation rate
      (ESR), and serum C-reactive protein and fibrinogen levels. Oral health-related
      QoL and general QoL were evaluated using oral health impact profile-14 (OHIP-14)
      and Medical Outcomes Short-Form Health Survey Questionnaire 36 (SF-36),
      respectively. RESULTS: Only the numbers of extracted teeth (4.13+/-4.72 vs.
      1.55+/-3.6) and filled teeth (2.33+/-3.19 vs. 0.66+/-1.46) were significantly
      higher in FMF group compared to HC group (p=0.005 and p=0.013, respectively).
      OHIP-14 score was significantly higher in FMF and BD groups compared to HC group.
      In FMF patients, OHIP-14 score was positively correlated with the number of
      extracted teeth (r=0.38, p=0.010), while the number of carious teeth was
      positively correlated with ESR (r=0.43, p=0.003). When FMF patients were sub
      classified according to disease severity, no significant difference was observed
      with respect to oral health status. CONCLUSIONS: In patients with FMF, some of
      the parameters of oral health status were found to be worse compared to HC group.
      Tooth loss appears to be to be a critical factor contributing to impaired oral
      QoL. In general, oral health status in FMF patients is better than in BD
      patients.

PMID- 23557977
TI  - Assessment of intramuscular activation patterns using ultrasound M-mode strain.
AB  - The intramuscular activation pattern can be connected to the motor unit
      recruitment strategy of force generation and fatigue resistance. Electromyography
      has earlier been used in several studies to quantify the spatial inhomogeneity of
      the muscle activation. We applied ultrasound M-mode strain to study the
      activation pattern through the tissue deformation. Correlation values of the
      strain at different force levels were used to quantify the spatial changes in the
      activation. The assessment was done including the biceps brachii muscle of 8
      healthy subjects performing isometric elbow flexion contractions ranging from 0%
      to 80% of maximum voluntary contraction. The obtained results were repeatable and
      demonstrated consistent changes of the correlation values during force
      regulation, in agreement with previously presented EMG-results. Both intra
      subject and inter-subject activation patterns of strain were considered along and
      transverse the fiber direction. The results suggest that ultrasound M-mode strain
      can be used as a complementary method to study intramuscular activation patterns
      with high spatial resolution. 

PMID- 23557978
TI  - Highly sensitive detection of thrombin using SERS-based magnetic aptasensors.
AB  - This paper reports a method of highly sensitive detection of thrombin using a
      surface-enhanced Raman scattering (SERS)-based magnetic aptasensor. Magnetic
      beads and gold nanoparticles (Au NPs) were used as supporting substrates and
      sensing probes, respectively. For this purpose, 15-mer thrombin-binding aptamers
      (TBA15) were immobilized onto the surface of magnetic beads, and then thrombin
      antigens and 29-mer thrombin-binding aptamer (TBA29)-conjugated Au NPs were
      sequentially added for the formation of sandwich aptamer complexes. Quantitative
      analysis was performed by monitoring the intensity variation of a characteristic
      SERS signal of Raman reporter molecules. Because all of the reactions occur in
      solution, this SERS-based immunoassay technique can solve the diffusion-limited
      kinetic problems on a solid substrate. The limit of detection (LOD) of thrombin,
      determined by the SERS-based aptasensor, was estimated to be 0.27pM. The proposed
      method is expected to be a good clinical tool for the diagnosis of a thrombotic
      disease.

PMID- 23557979
TI  - "Sugarcoated haws on a stick"-like MWNTs-Fe3O4-C coaxial nanomaterial: synthesis,
      characterization and application in electrochemiluminescence immunoassays.
AB  - In this paper, a carbon coated magnetic nanoparticle (Fe3O4-C) was first
      synthesized via solvothermal reaction and carbonization of glucose under
      hydrothermal condition. The electrochemiluminescence (ECL) property of Fe3O4-C
      was studied, and exhibited a peak at 1.21V. In the goal to amplify the ECL
      intensity for sensitive detection, a novel coaxial carbon coated magnetic
      nanomaterial (MWNTs-Fe3O4-C) was synthesized. Fourier transform infrared (FT-IR)
      spectroscopy, transmission electron microscopy (TEM), thermal gravimetric
      analysis (TGA), powder X-ray diffraction (XRD) and powder X-ray photoelectron
      spectrometry (XPS) were applied as powerful tools to characterize and to
      demonstrate the named nanomaterial. MWNTs-Fe3O4-C showed better ECL property than
      Fe3O4-C. Furthermore, an ultrasensitive ECL immunosensor based on MWNTs-Fe3O4-C
      was developed for the determination of carcinoembryonic antigen (CEA). The
      prepared ECL immunosensor exhibited high sensitivity, good reproducibility, long
      term stability, and acceptable precision on the detection of CEA in clinical
      human serum samples.

PMID- 23557980
TI  - Is there a role for intraoperative recurrent laryngeal nerve monitoring during
      high mediastinal lymph node dissection in three-stage oesophagectomy for
      oesophageal cancer?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether there is a role for intraoperative recurrent
      laryngeal nerve monitoring during high mediastinal lymph node dissection in three
      stage oesophagectomy for oesophageal cancer. A total of 125 papers were
      identified using the reported searches of which 2 represented the best evidence
      to answer the clinical question. The authors, journal, date, country of
      publication, study type, patient group, relevant outcomes and results are
      tabulated. Oesophageal surgery, similar to thyroid, parathyroid and
      cardiothoracic surgery poses a risk to the recurrent laryngeal nerves (RLN).
      Intraoperative RLN monitoring (IONM) is commonly being used in thyroid and
      parathyroid surgery in many centres. The same does not hold true for three-stage
      oesophagectomy with high mediastinal lymph node dissection despite the inherent
      risks to the RLN being much higher with this type of surgery. There are only a
      handful of studies in the literature evaluating the role of IONM in three-stage
      oesophagectomy. As a result, there is limited evidence to provide robust
      guidance. The evidence from the present review supports the use of IONM during
      high mediastinal lymph node dissection in three-stage oesophagectomy for
      oesophageal cancer. IONM appears to have a protective role for the RLN and also
      reduce the risk of postoperative pneumonia without adding to the operative time.
      In patients due to undergo three-stage oesophagectomy, the use of IONM of the RLN
      should be considered during the high mediastinal lymph node dissection and
      cervical access parts of the operation.

PMID- 23557981
TI  - Recurrence after groin hernia repair-revisited.
AB  - One of the commonly performed operations all over the world is hernia repair.
      Various open and laparoscopic procedures are available now for hernia repair.
      They are judged mainly by the recurrence rate following operation. The
      recognition of the causes of recurrence makes their prevention/elimination
      possible. Articles on hernia recurrence published in various journals over the
      past 40 years have been analysed. This review article mainly focuses on the
      causes of recurrence of hernia and their prevention. The causes of recurrence
      following open and laparoscopic hernia repair have been analysed. In open repair,
      early recurrences are due to faults in operative technique and postoperative
      infection. Late recurrences are due to patient factors like collagen defects, age
      and medical morbidities. In laparoscopic repair, technical aspects of surgery
      like dissection, mesh placement and fixation are the important factors which
      decide hernia recurrence.

PMID- 23557982
TI  - A systematic review to evaluate the effectiveness of carnitine supplementation in
      improving walking performance among individuals with intermittent claudication.
AB  - OBJECTIVE: To evaluate the evidence for the use of carnitine supplementation in
      improving walking performance among individuals with intermittent claudication.
      DESIGN: Systematic review. METHODS: An electronic search of the literature was
      performed using MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled
      Trials and The Cochrane Library from inception through to November 2012. Search
      terms included peripheral arterial disease, intermittent claudication and
      carnitine. Reference lists of review articles and primary studies were also
      examined. Full reports of published experimental studies including randomized
      controlled trials and pre-test/post-test trials were selected for inclusion. A
      quality assessment was undertaken according to the Jadad scale. RESULTS: A total
      of 40 articles were retrieved, of which 23 did not meet the inclusion criteria.
      The 17 included articles reported on a total of 18 experimental studies of
      carnitine supplementation (5 pre-test/post-test; 8 parallel RCT; 5 cross-over
      RCT) for improving walking performance in adults with intermittent claudication.
      For pre-test/post-test studies, 300-2000 mg propionyl-L-carnitine (PLC) was
      administered orally or intravenously for a maximum of 90 days (7-42 participants)
      with statistically significant improvements of between 74 m and 157 m in pain
      free walking distance and between 71 m and 135 m in maximal walking distance
      across 3 out of 5 studies. Similarly, PLC (600 mg-3000 mg) was administered
      orally in 7 out of 8 parallel RCTs (22-485 participants), the longest duration
      being 12 months. All but one of the smallest trials demonstrated statistically
      significant improvements in walking performance between 31 and 54 m greater than
      placebo for pain free walking distance and between 9 and 86 m greater than
      placebo for maximal walking distance. A double-blind parallel RCT of cilostazol
      plus 2000 mg oral L-carnitine or placebo for 180 days (145 participants) did not
      demonstrate any significant improvement in walking performance. Of 5 cross-over
      RCTs (8-20 participants), 4 demonstrated significant improvements in walking
      performance following administration of 300-6000 mg L-carnitine or PLC. Compared
      to placebo, pain free walking distance and maximal walking distance improved by
      23-132 m and 104 m respectively following carnitine intervention. CONCLUSIONS:
      Most trials demonstrated a small or modest improvement in walking performance
      with administration of PLC or L-carnitine. These findings were largely
      independent of level or quality of evidence, while there was some evidence that
      intravenous administration was more effective than oral administration and those
      with severe claudication may achieve greater benefits than those with moderate
      claudication. Routine carnitine supplementation in the form of PLC may therefore
      be a useful adjunct therapy for management of intermittent claudication. Further
      research is warranted to determine the optimal form, duration, dose and safety of
      carnitine supplementation across the spectrum of peripheral arterial disease
      severity and its effect with concurrent supervised exercise programs and best
      medical therapy. These studies should be supplemented with cost effectiveness
      studies to ensure that the return on the investment is acceptable.

PMID- 23557983
TI  - Modeling offenses among motorcyclists involved in crashes in Spain.
AB  - In relative terms, Spanish motorcyclists are more likely to be involved in
      crashes than other drivers and this tendency is constantly increasing. The
      objective of this study is to identify the factors that are related to being an
      offender in motorcycle accidents. A binary logit model is used to differentiate
      between offender and non-offender motorcyclists. A motorcyclist was considered to
      be offender when s/he had committed at least one traffic offense at the moment
      previous to the crash. The analysis is based on the official accident database of
      the Spanish general directorate of traffic (DGT) for the 2003-2008 time period. A
      number of explanatory variables including motorcyclist characteristics and
      environmental factors have been evaluated. The results suggest that
      inexperienced, older females, not using helmets, absent-minded and non-fatigued
      riders are more likely to be offenders. Moreover, riding during the night, on
      weekends, for leisure purposes and along roads in perfect condition, mainly on
      curves, predict offenses among motorcyclists. The findings of this study are
      expected to be useful in developing traffic policy decisions in order to improve
      motorcyclist safety.

PMID- 23557984
TI  - Safety assessment of food and feed from biotechnology-derived crops employing RNA
      mediated gene regulation to achieve desired traits: a scientific review.
AB  - Gene expression can be modulated in plants to produce desired traits through
      agricultural biotechnology. Currently, biotechnology-derived crops are compared
      to their conventional counterparts, with safety assessments conducted on the
      genetic modification and the intended and unintended differences. This review
      proposes that this comparative safety assessment paradigm is appropriate for
      plants modified to express mediators of RNA-mediated gene regulation, including
      RNA interference (RNAi), a gene suppression mechanism that naturally occurs in
      plants and animals. The molecular mediators of RNAi, including long double
      stranded RNAs (dsRNA), small interfering RNAs (siRNA), and microRNAs (miRNA),
      occur naturally in foods; therefore, there is an extensive history of safe
      consumption. Systemic exposure following consumption of plants containing dsRNAs
      that mediate RNAi is limited in higher organisms by extensive degradation of
      ingested nucleic acids and by biological barriers to uptake and efficacy of
      exogenous nucleic acids. A number of mammalian RNAi studies support the concept
      that a large margin of safety will exist for any small fraction of RNAs that
      might be absorbed following consumption of foods from biotechnology-derived
      plants that employ RNA-mediated gene regulation. Food and feed derived from these
      crops utilizing RNA-based mechanisms is therefore expected to be as safe as food
      and feed derived through conventional plant breeding.

PMID- 23557985
TI  - Cell viability score (CVS) as a good indicator of critical concentration of
      benzalkonium chloride for toxicity in cultured ocular surface cell lines.
AB  - Cytotoxicity of benzalkonium chloride (BAK) is a major factor affecting drug
      cytotoxicity. This study aimed to determine the critical concentration of BAK for
      cultured ocular cells, using SIRC (rabbit corneal epithelium), BCE C/D-1b (bovine
      corneal epithelial cells), RC-1 (rabbit corneal epithelium), and Chang (human
      conjunctival cells). Cell viability was determined following the exposure of
      cells to 11 concentrations of BAK for 10, 30, or 60 min using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and neutral red
      assays, and the cell viability score (CVS) was used to evaluate comprehensively
      the toxicity of BAK. The CVS system consists of two values. The CVS50 was
      determined by the number of measurements for viability >=50% of control. The
      CVS40/80 was calculated as follows: CVS40/80=(number of measurements for
      viability values >80%)-(number of measurements for viability values <40%). Both
      %CVS50 and %CVS40/80 decreased with concentrations of BAK. When BAK
      concentrations were 0.01% or higher, %CVS50 and %CVS40/80 became 0 and less than 
      90, respectively. Meanwhile, when BAK concentrations were 0.001% or lower, %CVS50
      became 100. In the case of %CVS40/80, when the BAK concentrations were 0.002% or
      lower, the values reached 75 or more, and when 0.0005% or lower, the %CVS40/80
      value reached 100. Accordingly, BAK induced very low cytotoxicity in the cultured
      ocular cell lines at concentrations of 0.002% or lower. The concentration
      dependency confirmed that the CVS score is useful for expressing drug
      cytotoxicity in a simple and comprehensive manner.

PMID- 23557986
TI  - TSNA levels in machine-generated mainstream cigarette smoke: 35 years of data.
AB  - This paper characterizes historical and current tobacco specific nitrosamine
      (TSNA) levels in mainstream (MS) cigarette smoke of US commercial cigarettes. To
      conduct this analysis, we gathered 35 years of published data of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN)
      levels in MS cigarette smoke. We also assessed internal data of MS smoke NNK and
      NNN levels generated from various market monitoring initiatives and from control
      cigarettes used in a multi-year program for testing cigarette ingredients. In
      all, we analyzed machine smoking data from 401 cigarette samples representing a
      wide range of products and design characteristics from multiple manufacturers and
      market leaders. There was no indication that TSNA levels systematically increased
      in cigarette MS smoke over the 35-year analysis period. In particular, TSNA
      levels expressed as either per cigarette or normalized for tar suggest a downward
      trend in MS smoke over the past 10 years. The apparent downward trend in TSNA
      levels in MS smoke may reflect industry and agricultural community efforts to
      reduce levels of TSNAs in tobacco and cigarette smoke.

PMID- 23557987
TI  - Decreased ovarian function is associated with obesity in very long-term female
      survivors of childhood cancer.
AB  - OBJECTIVE: Obesity and gonadal dysfunction are known major side effects of
      treatment in adult childhood cancer survivors (CCS). In the general population,
      obesity has a negative influence on female fertility. We aimed to evaluate
      whether obesity and serum insulin are associated with decreased ovarian reserve
      markers in CCS. DESIGN: Retrospective single-center cohort study. METHODS: Data
      of 191 female survivors of childhood cancer were analyzed. Median follow-up time
      was 18.8 (2.348.8) years. Outcome measures were serum anti-Mullerian hormone
      (AMH) and total follicle count (FC). Potential risk factors were: BMI; body
      composition measures, determined by dual-energy X-ray absorptiometry (total fat
      percentage, lean body mass, and visceral fat percentage); and fasting insulin.
      RESULTS: Lower serum AMH was found in obese subjects (beta (%) -49, P=0.007) and
      in subjects with fasting insulin in the highest tertile (beta (%) -43, P=0.039).
      Total fat percentage tends to be associated with serum AMH (beta (%) -2.1,
      P=0.06). Survivors in the highest tertile of insulin had significantly lower FC
      than survivors in the lowest tertile (beta -6.3, P=0.013). BMI and other measures
      of body composition were not associated with FC. Correlation between serum AMH
      and antral follicle count (AFC) was rho=0.32 (P=0.08). CONCLUSIONS: Obesity and
      insulin resistance are associated with gonadal damage, as reflected by decreased
      AMH and reduced FC in adult survivors of childhood cancer. In contrast to its
      highly predictive value for AFC in the healthy female population, serum AMH does
      not seem to correlate as well with AFC in CCS.

PMID- 23557988
TI  - The clinical significance and primary determinants of hirsutism in patients with
      polycystic ovary syndrome.
AB  - OBJECTIVE: Hirsutism is frequently present in patients with polycystic ovary
      syndrome (PCOS) and is a major sign of hyperandrogenism. However, other disorders
      frequently present in PCOS, particularly abdominal obesity and insulin resistance
      (IR), have also been implicated in the development of hirsutism in this
      population but relevant data are limited. We aimed to define the determinants of
      the presence of hirsutism in PCOS. DESIGN: Observational study. METHODS: We
      studied 1297 patients with PCOS (age 24.3+/-5.8 years, BMI 26.8+/-6.9 kg/m(2)).
      Hirsutism was defined as a modified Ferriman-Gallwey score >=8. RESULTS: Women
      with hirsutism were younger, had greater BMI, and had higher levels of
      circulating androgens than women without hirsutism; markers of IR did not differ
      between the two groups after adjustment for age and BMI. The prevalence of
      hirsutism progressively declined with age, was lower in normal-weight women than
      in overweight and obese women, and was comparably prevalent in the
      hyperandrogenemic phenotypes of PCOS. In binary logistic regression analysis,
      independent predictors of the presence of hirsutism were younger age, larger
      waist circumference (W), and higher serum testosterone levels. In stepwise linear
      regression analysis, the Ferriman-Gallwey score independently correlated with
      age, W, free androgen index, and serum Delta4-androstenedione and DHEAS levels.
      CONCLUSIONS: Besides hyperandrogenemia, abdominal obesity, and young age are
      independently associated with the presence of hirsutism. In contrast, the
      relationship between IR and hirsutism appears to be mediated by the more severe
      obesity of insulin-resistant patients with PCOS.

PMID- 23557990
TI  - Quantitative model analysis with diverse biological data: applications in
      developmental pattern formation.
AB  - Mathematical modeling of transcription factor and signaling networks is widely
      used to understand if and how a mechanism works, and to infer regulatory
      interactions that produce a model consistent with the observed data. Both of
      these approaches to modeling are informed by experimental data, however, much of
      the data available or even acquirable are not quantitative. Data that is not
      strictly quantitative cannot be used by classical, quantitative, model-based
      analyses that measure a difference between the measured observation and the model
      prediction for that observation. To bridge the model-to-data gap, a variety of
      techniques have been developed to measure model "fitness" and provide numerical
      values that can subsequently be used in model optimization or model inference
      studies. Here, we discuss a selection of traditional and novel techniques to
      transform data of varied quality and enable quantitative comparison with
      mathematical models. This review is intended to both inform the use of these
      model analysis methods, focused on parameter estimation, and to help guide the
      choice of method to use for a given study based on the type of data available.
      Applying techniques such as normalization or optimal scaling may significantly
      improve the utility of current biological data in model-based study and allow
      greater integration between disparate types of data. 

PMID- 23557989
TI  - A new method for stranded whole transcriptome RNA-seq.
AB  - This report describes an improved protocol to generate stranded, barcoded RNA-seq
      libraries to capture the whole transcriptome. By optimizing the use of duplex
      specific nuclease (DSN) to remove ribosomal RNA reads from stranded barcoded
      libraries, we demonstrate improved efficiency of multiplexed next generation
      sequencing (NGS). This approach detects expression profiles of all RNA types,
      including miRNA (microRNA), piRNA (Piwi-interacting RNA), snoRNA (small nucleolar
      RNA), lincRNA (long non-coding RNA), mtRNA (mitochondrial RNA) and mRNA
      (messenger RNA) without the use of gel electrophoresis. The improved protocol
      generates high quality data that can be used to identify differential expression
      in known and novel coding and non-coding transcripts, splice variants,
      mitochondrial genes and SNPs (single nucleotide polymorphisms).

PMID- 23557991
TI  - Stochastic models of transcription: from single molecules to single cells.
AB  - Genes in prokaryotic and eukaryotic cells are typically regulated by complex
      promoters containing multiple binding sites for a variety of transcription
      factors leading to a specific functional dependence between regulatory inputs and
      transcriptional outputs. With increasing regularity, the transcriptional outputs
      from different promoters are being measured in quantitative detail in single-cell
      experiments thus providing the impetus for the development of quantitative models
      of transcription. We describe recent progress in developing models of
      transcriptional regulation that incorporate, to different degrees, the complexity
      of multi-state promoter dynamics, and its effect on the transcriptional outputs
      of single cells. The goal of these models is to predict the statistical
      properties of transcriptional outputs and characterize their variability in time
      and across a population of cells, as a function of the input concentrations of
      transcription factors. The interplay between mathematical models of different
      regulatory mechanisms and quantitative biophysical experiments holds the promise
      of elucidating the molecular-scale mechanisms of transcriptional regulation in
      cells, from bacteria to higher eukaryotes. 

PMID- 23557992
TI  - Re-emergence of papulonodular napkin dermatitis with use of reusable diapers:
      report of 5 cases.
AB  - The use of reusable diapers, often made of cotton and bamboo material, is
      becoming more widespread in France--with the "eco" fashion, as they are
      considered more natural, ecologic and economic. We report 5 cases of
      papulonodular lesions in convex skin areas associated with the use of these
      diapers in infants. One case was typical Sevestre and Jacquet erosive dermatitis.
      The 4 others presented skin-coloured umbilicated papules or nodules with slight
      or no erythema and could be considered early-stage Sevestre and Jacquet erosive
      dermatitis, granuloma gluteale (1 case) or pseudo-verrucous papules. These 3
      diagnoses probably belong to the same disease spectrum, proposed as "irritant
      napkin papulonodules". Napkin lesions occurred subsequent to 1) in all cases, use
      of reusable diapers, which are probably less absorbent than disposable diapers;
      2) in 2 cases, insufficient food, which was responsible for lack of weight gain
      and delayed healing; and 3) in 1 case, diarrhea, which worsened the moisture. We
      alert physicians to possible papulonodular napkin dermatitis in infants wearing
      reusable diapers.

PMID- 23557994
TI  - Anti-TNF-alpha therapy itself does not trigger Guillain-Barre syndrome.

PMID- 23557993
TI  - A diarylheptanoid phytoestrogen from Curcuma comosa, 1,7-diphenyl-4,6-heptadien-3
      ol, accelerates human osteoblast proliferation and differentiation.
AB  - Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms.
      Previous work showed that C. comosa extracts protect mice from ovariectomy
      induced osteopenia with minimal effects on reproductive organs, and identified
      the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the
      major active component of C. comosa rhizomes. At 1-10MUM, DPHD increased
      differentiation in transformed mouse osteoblasts, but the effect of DPHD on
      normal bone cells was unknown. We examined the concentration dependency and
      mechanism of action of DPHD relative to 17beta-estradiol in nontransformed human
      osteoblasts (h-OB). The h-OB were 10-100 fold more sensitive to DPHD than
      transformed osteoblasts: DPHD increased h-OB proliferation at 10nM and, at 100nM,
      activated MAP kinase signaling within 30 min. In long-term differentiation
      assays, responses of h-OB to DPHD were significant at 10nM, and optimal response
      in most cases was at 100 nM. At 7-21 days, DPHD accelerated osteoblast
      differentiation, indicated by alkaline phosphatase activity and osteoblast
      specific mRNA production. Effects of DPHD were eliminated by the estrogen
      receptor antagonist ICI182780. During differentiation, DPHD promoted early
      expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently,
      DPHD accelerated production of bone structural genes, including COL1A1 and
      osteocalcin comparably to 17beta-estradiol. In h-OB, DPHD increased the
      osteoprotegerin to RANKL ratio and supported mineralization more efficiently than
      10nM 17beta-estradiol. We conclude that DPHD promotes human osteoblast function
      in vitro effectively at nanomolar concentrations, making it a promising compound
      to protect bone in menopausal women.

PMID- 23557995
TI  - Iron oxide nanoparticles in geomicrobiology: from biogeochemistry to
      bioremediation.
AB  - Iron oxides are important constituents of soils and sediments and microbial iron
      reduction is considered to be a significant anaerobic respiration process in the
      subsurface, however low microbial reduction rates of macroparticulate Fe oxides
      in laboratory studies led to an underestimation of the role of Fe oxides in the
      global Fe redox cycle. Recent studies show the high potential of nano-sized Fe
      oxides in the environment as, for example, electron acceptor for microbial
      respiration, electron shuttle between different microorganisms, and scavenger for
      heavy metals. Biotic and abiotic reactivity of iron macroparticles differ
      significantly from nano-sized Fe oxides, which are usually much more reactive.
      Factors such as particle size, solubility, ferrous iron, crystal structure, and
      organic molecules were identified to influence the reactivity. This review
      discusses factors influencing the microbial reactivity of Fe oxides. It
      highlights the differences between natural and synthetic Fe oxides especially
      regarding the presence of organic molecules such as humic acids and natural
      organic matter. Attention is given to the transport behavior of Fe oxides in
      laboratory systems and in the environment, because of the high affinity of
      different contaminants to Fe oxide surfaces and associated co-transport of
      pollutants. The high reactivity of Fe oxides and their potential as adsorbents
      for different pollutants are discussed with respect to application and
      development of remediation technologies. 

PMID- 23557996
TI  - Role of the animal model on the pharmacokinetics of equine-derived antivenoms.
AB  - Antivenom pharmacokinetics has been studied in heterologous models in which the
      animal species used as immunoglobulin source is different from that used as
      recipient. In these models, after intravenous administration of antivenom, the
      plasma concentration of immunoglobulins shows a rapid initial declining-phase
      followed by a slower terminal-phase, which has been associated with antivenom
      distribution and elimination, respectively. We have compared pharmacokinetic
      parameters for equine-derived antivenom in homologous (horse) and heterologous
      (cow) models. It was found that the maximum concentration is lower in cows than
      in horses. Additionally, the steady-state distribution volume is higher in cows
      as compared to horses. On the other hand, models were not different in the time
      required to reach the maximum concentration, the area under the
      concentration/time curve, the half-life of decay during the slowest phase, the
      systemic clearance and the mean residence time. Similar results were obtained in
      a rabbit model, in which the pharmacokinetics was also affected by passive
      immunization of rabbits with anti-equine IgG. We conclude that, in addition to
      other physiological differences (e.g. cardiac frequency, plasmatic volume,
      glomerular filtration rate, etc.) between animal models, the ability to remove
      foreign immunoglobulins might influence the way in which the plasma concentration
      of antivenom decreases over time, thereby distorting the pharmacokinetic
      predictions based on non-compartmental models.

PMID- 23557997
TI  - A proposal for a pathogenesis-seeking animal model of Takotsubo syndrome.

PMID- 23557998
TI  - Role of baseline echocardiography in preoperative management of liver transplant
      candidates.

PMID- 23557999
TI  - Reply: To PMID 23021513.

PMID- 23558000
TI  - "Reverse McConnell's sign?": a unique right ventricular feature of Takotsubo
      cardiomyopathy.

PMID- 23558001
TI  - Process to write American College of Cardiology Foundation/American Heart
      Association guidelines in need of overhaul.

PMID- 23558002
TI  - Seattle Heart Failure Model.

PMID- 23558003
TI  - The clinical utility of electrophysiological study to predict adverse outcomes in
      patients with arrhythmogenic right ventricular cardiomyopathy.

PMID- 23558004
TI  - The German CPU Registry: comparison of troponin positive to troponin negative
      patients.

PMID- 23558005
TI  - Bioresorbable scaffold in myocardial infarction: has the time come?

PMID- 23558006
TI  - A novel ACLS team leader checklist implemented to improve resuscitation efforts.

PMID- 23558007
TI  - In vitro antifungal susceptibility and molecular identity of 99 clinical isolates
      of the opportunistic fungal genus Curvularia.
AB  - The in vitro antifungal susceptibility of a set of 99 clinical isolates of
      Curvularia was tested against 9 drugs using a reference microdilution method. The
      isolates had been identified previously to species level by comparing their ITS
      rDNA and glyceraldehyde-3-phosphate dehydrogenase gene sequences with those of
      reference strains. We were able to reliably identify 73.2% of the isolates, the
      most frequent species being Curvularia aeria, Curvularia geniculata/Curvularia
      senegalensis, Curvularia lunata, Curvularia inaequalis, Curvularia verruculosa,
      and Curvularia borreriae. Most of these isolates had been recovered from nasal
      sinus, which is generally considered one of the most frequent sites of infection
      by these fungi. In addition, at least 3 phylogenetic species that have not yet
      been formally described were detected. The most active drugs were the
      echinocandins, amphotericin B, and posaconazole, whereas voriconazole and
      itraconazole showed poor activity.

PMID- 23558008
TI  - Ethylene emission and PR protein synthesis in ACC deaminase producing
      Methylobacterium spp. inoculated tomato plants (Lycopersicon esculentum Mill.)
      challenged with Ralstonia solanacearum under greenhouse conditions.
AB  - Bacteria of genus Methylobacterium have been found to promote plant growth and
      regulate the level of ethylene in crop plants. This work is aimed to test the
      induction of defense responses in tomato against bacterial wilt by stress
      ethylene level reduction mediated by the ACC deaminase activity of
      Methylobacterium strains. Under greenhouse conditions, the disease index value in
      Methylobacterium sp. inoculated tomato plants was lower than control plants.
      Plants treated with Methylobacterium sp. challenge inoculated with Ralstonia
      solanacearum (RS) showed significantly reduced disease symptoms and lowered
      ethylene emission under greenhouse condition. The ACC and ACO (1
      aminocyclopropane-1-carboxylate oxidase) accumulation in tomato leaves were
      significantly reduced with Methylobacterium strains inoculation. While ACC
      oxidase gene expression was found higher in plants treated with R. solanacearum
      than Methylobacterium sp. treatment, PR proteins related to induced systemic
      resistance like beta-1,3-glucanase, PAL, PO and PPO were increased in
      Methylobacterium sp. inoculated plants. A significant increase in beta-1,3
      glucanase and PAL gene expression was found in all the Methylobacterium spp.
      treatments compared to the R. solanacearum treatment. This study confirms the
      activity of Methylobacterium sp. in increasing the defense enzymes by modulating
      the ethylene biosynthesis pathway and suggests the use of methylotrophic bacteria
      as potential biocontrol agents in tomato cultivation. 

PMID- 23558009
TI  - Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in
      mice.
AB  - Chronic pancreatitis (CP) is a devastating disease characterized by persistent
      and uncontrolled abdominal pain. Our lack of understanding is partially due to
      the lack of experimental models that mimic the human disease and also to the lack
      of validated behavioral measures of visceral pain. The ligand-gated cation
      channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and
      pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis
      and sustained pancreatic pain. We induced CP by injecting the chemical agent
      trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis,
      into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic
      inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS
      injection caused marked pancreatic fibrosis with increased collagen-staining
      intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic
      stellate cell activation, and these changes were reflected by increased
      histological damage scores. TNBS-injected animals showed mechanical
      hypersensitivity during von Frey filament probing of the abdomen, decreased daily
      voluntary wheel-running activity, and increased immobility scores during open
      field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal
      to von Frey filament probing, suggesting central sensitization. Inflammatory
      changes and pain indexes were significantly reduced in trpa1(-/-) mice. In
      conclusion, we have characterized in mice a model of CP that resembles the human
      condition, with marked histological changes and behavioral measures of pain. We
      have demonstrated, using novel and objective pain measurements, that TRPA1
      mediates inflammation and visceral hypersensitivity in CP and could be a
      therapeutic target for the treatment of sustained inflammatory abdominal pain.

PMID- 23558010
TI  - Pharmacological inhibition to examine the role of DGAT1 in dietary lipid
      absorption in rodents and humans.
AB  - Alterations in fat metabolism, in particular elevated plasma concentrations of
      free fatty acids and triglycerides (TG), have been implicated in the pathogenesis
      of Type 2 diabetes, obesity, and cardiovascular disease. Acyl-CoA:diacylglycerol
      acyltransferase 1 (DGAT1), a member of the large family of membrane-bound O
      acyltransferases, catalyzes the final step in triacylglycerol formation. In the
      intestine, DGAT1 is one of the acyltransferases responsible for the
      reesterficiation of dietary TG. Following a single dose of a selective
      pharmacological inhibitor of DGAT1, PF-04620110, a dose-dependent inhibition of
      TG and vitamin A absorption postprandially was demonstrated in rodents and human
      subjects. In C57/BL6J mice, acute DGAT1 inhibition alters the temporal and
      spatial pattern of dietary lipid absorption. To understand the impact of DGAT1
      inhibition on enterocyte lipid metabolism, lipomic profiling was performed in rat
      intestine and plasma as well as human plasma. DGAT1 inhibition causes an
      enrichment of polyunsaturated fatty acids within the TG class of lipids. This
      pharmacological intervention gives us insight as to the role of DGAT1 in human
      dietary lipid absorption.

PMID- 23558013
TI  - The onset of sensitivity to horizontal disparity in infancy: a short-term
      longitudinal study.
AB  - In this short-term longitudinal study, infants were examined for their natural
      preference of a square defined by crossed horizontal disparity (either 1 degrees 
      or 0.5 degrees ) over a square defined by a vertical disparity (either 1 degrees 
      or 0.5 degrees ). The square targets were embedded in a dynamic random dot
      stereogram. The stimuli were presented on an autostereoscopic monitor equipped
      with a face-tracking device. The infants were tested weekly between 6 and 16
      weeks of age. Four experiments were conducted. In two experiments, the infants
      were examined with the forced-choice preferential looking (FPL) method for their
      ability to perceive either 1 degrees  or 0.5 degrees  horizontal disparity. In
      the remaining two experiments, the classical natural preference (CNP) method
      (measurement of looking times) was applied. According to the results of the FPL
      experiments, mean relative preference for the horizontal disparity square became
      significant at 8 weeks of age. The CNP data indicated an onset of stereopsis at
      12-15 weeks. The mean relative preferences for horizontal disparity indicated by
      the CNP method were smaller than those found in the FPL experiments. Thus, the
      FPL method was more sensitive than the CNP method in the measurement of infant
      responsiveness to crossed horizontal disparity.

PMID- 23558012
TI  - Developing a reproducible method for the high-resolution separation of peritoneal
      dialysate proteins on 2-D gels.
AB  - PURPOSE: Despite recent progress in the proteomic analysis of peritoneal
      dialysate effluent (PDE), there remains unresolved problems in the development of
      an optimal sample preparation method. EXPERIMENTAL DESIGN: We examined five
      protocols for concentrating PDE proteins and the effects of immobilized pH
      gradient (IPG) strips with different pH ranges and sample loading techniques. In
      addition, we examined three kits for depleting high abundance proteins by SDS
      PAGE and two-dimensional gel electrophoresis (2-DE). RESULTS: PDE proteins
      precipitated with 75% acetonitrile (ACN) showed the greatest number of protein
      spots by 2-DE, with over 800 distinct spots. Higher-resolution images were
      obtained using IPG strips with a pH range of 4-7. The ProteoPrep immunoaffinity
      albumin and IgG depletion kit removed high abundance proteins with higher
      efficiency and more compatibility with isoelectric focusing (IEF). Removing high
      abundance proteins also increased the resolution and improved the intensity of
      low abundance proteins. CONCLUSION AND CLINICAL RELEVANCE: High-resolution 2-DE
      images of PDE proteins were obtained by concentrating samples with 75% ACN, using
      pH 4-7 IPG strips, and depleting high abundance proteins. This optimized method
      will enable future studies to discover predictive biomarkers of disease in
      patients on dialysis.

PMID- 23558011
TI  - Preterm human milk contains a large pool of latent TGF-beta, which can be
      activated by exogenous neuraminidase.
AB  - Human milk contains substantial amounts of transforming growth factor (TGF)-beta,
      particularly the isoform TGF-beta2. We previously showed in preclinical models
      that enterally administered TGF-beta2 can protect against necrotizing
      enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this
      study we hypothesized that premature infants remain at higher risk of NEC than
      full-term infants, even when they receive their own mother's milk, because
      preterm human milk contains less bioactive TGF-beta than full-term milk. Our
      objective was to compare TGF-beta bioactivity in preterm vs. full-term milk and
      identify factors that activate milk-borne TGF-beta. Mothers who delivered between
      23 0/7 and 31 6/7 wk or at >=37 wk of gestation provided milk samples at serial
      time points. TGF-beta bioactivity and NF-kappaB signaling were measured using
      specific reporter cells and in murine intestinal tissue explants. TGF-beta1, TGF
      beta2, TGF-beta3, and various TGF-beta activators were measured by real-time PCR,
      enzyme immunoassays, or established enzymatic activity assays. Preterm human milk
      showed minimal TGF-beta bioactivity in the native state but contained a large
      pool of latent TGF-beta. TGF-beta2 was the predominant isoform of TGF-beta in
      preterm milk. Using a combination of several in vitro and ex vivo models, we show
      that neuraminidase is a key regulator of TGF-beta bioactivity in human milk.
      Finally, we show that addition of bacterial neuraminidase to preterm human milk
      increased TGF-beta bioactivity. Preterm milk contains large quantities of TGF
      beta, but most of it is in an inactive state. Addition of neuraminidase can
      increase TGF-beta bioactivity in preterm milk and enhance its anti-inflammatory
      effects.

PMID- 23558014
TI  - Case 3--2013: Maldistribution of cardioplegia detected by transesophageal
      echocardiography during minimally invasive cardiac surgery.

PMID- 23558015
TI  - Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in
      HIV-2, a naturally contained human retroviral infection.
AB  - While a significant proportion of HIV-2-infected individuals are asymptomatic and
      maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and
      are predicted by detectable viremia. Identifying immune correlates that
      distinguish these 2 groups should provide insights into how a potentially
      pathogenic retrovirus can be naturally controlled. We performed a detailed study
      of HIV-2-specific cellular responses in a unique community cohort in Guinea
      Bissau followed for over 2 decades. T-cell responses were compared between
      controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides,
      major histocompatibility complex class I tetramers, and multiparameter flow
      cytometry. HIV-2 viral control was significantly associated with a high
      magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with
      greater perforin upregulation. This potentially protective HIV-2-specific
      response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an
      earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do
      not contain high levels of cytolytic markers, and exhibit low levels of
      activation and proliferation, representing distinct properties from CD8(+) T
      cells associated with HIV-1 control. These data reveal the potential T-cell
      correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T
      cells in a naturally contained retroviral infection.

PMID- 23558017
TI  - Micelle-monomer equilibria in solutions of ionic surfactants and in ionic
      nonionic mixtures: a generalized phase separation model.
AB  - On the basis of a detailed physicochemical model, a complete system of equations
      is formulated that describes the equilibrium between micelles and monomers in
      solutions of ionic surfactants and their mixtures with nonionic surfactants. The
      equations of the system express mass balances, chemical and mechanical
      equilibria. Each nonionic surfactant is characterized by a single thermodynamic
      parameter--its micellization constant. Each ionic surfactant is characterized by
      three parameters, including the Stern constant that quantifies the counterion
      binding. In the case of mixed micelles, each pair of surfactants is characterized
      with an interaction parameter, beta, in terms of the regular solution theory. The
      comparison of the model with experimental data for surfactant binary mixtures
      shows that beta is constant--independent of the micelle composition and
      electrolyte concentration. The solution of the system of equations gives the
      concentrations of all monomeric species, the micelle composition, ionization
      degree, surface potential and mean area per head group. Upon additional
      assumptions for the micelle shape, the mean aggregation number can be also
      estimated. The model gives quantitative theoretical interpretation of the
      dependence of the critical micellization concentration (CMC) of ionic surfactants
      on the ionic strength; of the CMC of mixed surfactant solutions, and of the
      electrolytic conductivity of micellar solutions. It turns out, that in the
      absence of added salt the conductivity is completely dominated by the
      contribution of the small ions: monomers and counterions. The theoretical
      predictions are in good agreement with experimental data.

PMID- 23558016
TI  - Naive B-cell trafficking is shaped by local chemokine availability and LFA-1
      independent stromal interactions.
AB  - It is not known how naive B cells compute divergent chemoattractant signals of
      the T-cell area and B-cell follicles during in vivo migration. Here, we used two
      photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G
      protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration,
      as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not
      influence parenchymal B-cell motility and distribution, despite their role during
      B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell
      motility in follicles and in the T-cell area. B-cell migration in the T-cell area
      followed a random guided walk model, arguing against directed migration in vivo.
      LFA-1, but not alpha4 integrins, contributed to B-cell motility in PLNs. However,
      stromal network guidance was LFA-1 independent, uncoupling integrin-dependent
      migration from stromal attachment. Finally, we observed that despite a 20-fold
      reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained
      essential for B-cell screening of antigen-presenting cells. Our data provide an
      overview of the contribution of prototype GPCRs and integrins during naive B-cell
      migration and shed light on the local chemokine availability that these cells
      compute.

PMID- 23558018
TI  - Influence of psoriasis on work.
AB  - BACKGROUND: Previous research indicates that psoriasis has an impact on early
      retirement, sick leave days and reduced work performance. OBJECTIVES: To evaluate
      the disadvantages at work caused by psoriasis. MATERIAL AND METHODS: The sample
      was based on patients visiting the dermatology outpatient clinic in Turku
      University Hospital. 262 returned a mailed questionnaire. The subjects were asked
      how many hours they were on a sick leave (absenteeism) and working while sick
      (presenteeism) due to psoriasis and other health reasons. RESULTS: Of the
      retired, 17.0% felt they were retired due to psoriasis. Those in the active work
      force reported on average 4.5 hours absenteeism and 8.3 hours of presenteeism due
      to psoriasis during the last 4 weeks. Psoriasis caused 27.0% of the total
      absenteeism and 39.0% of presenteeism. More than a quarter (28.9%) had been
      forced to modify their work due to psoriasis, most frequently to make the work
      less irritating for the skin. CONCLUSION: Psoriasis has a negative effect on
      patients' work in many ways, causing early retirement from work, sick leave days,
      change of occupation and work modifications.

PMID- 23558019
TI  - Evaluating of bone healing around porous coated titanium implant and potential
      systematic bias on the traditional sampling method.
AB  - INTRODUCTION: The mechanical properties of bone can largely be explained by bone
      density and the anisotropic orientation of the trabecular bone. The type of
      trabecular structure plays an important role in determining the mechanical
      properties of cancellous bone. Gap-healing and implant fixation could be affected
      by the various quality and quantity of bone in the local environment. Thus,
      implant fixation in one part might differ from the other part of the implant.
      This study aimed to investigate the influence of the sampling method on data
      evaluation. MATERIAL AND METHODS: Titanium alloy implants (Biomet Inc.) of 10mm
      in length and 6mm in diameter were inserted bilaterally into the proximal humerus
      of 8 skeletally mature sheep. Thus two implants with a concentric gap of 2mm were
      implanted in each sheep. The gap was filled with allograft. Standardised surgical
      procedure was used. At sacrifice, 6 weeks after surgery, both proximal humeri
      were harvested. The specimens were randomized to superficial or profound groups.
      In the superficial group, mechanical testing or histological analysis was carried
      out on the superficial part of the implant. In the profound group, the mechanical
      testing or histological analysis was performed on the profound part of the
      implant. RESULT: The mechanical fixation, bone volume and bone ongrowth showed no
      statistically significant differences. Mechanical test demonstrated a slight
      tendency to increased strength and failure energy were observed in the
      superficial group. Histomorphomety revealed bone ongrowth was slightly increased
      and volume fraction was decreased in the profound group. CONCLUSION: Histological
      analysis and mechanical testing can be applied to the superficial or profound
      part of the implant.

PMID- 23558020
TI  - Transverse myelitis in Behcet's disease: a series of four cases and review of the
      literature.
AB  - OBJECTIVES: Transverse myelitis (TM) is an uncommon neurologic condition
      characterised by the segmental involvement of the spinal cord. Although its
      etiology is unknown, a well established list of associations have been described,
      many items of which point towards an autoimmune and vasculitic process. TM is
      also a rare complication of Behcet's disease (BD), an autoimmune process. Herein
      we present 4 cases of TM associated with BD. METHODS: Retrospective chart reviews
      of 104 patients were done. Diagnosis of BD was established in each case according
      to the diagnostic criteria established by the International Study Group for
      Behcet's Disease. Demographic data, clinical and radiologic presentations of TM,
      treatment strategies and outcomes were obtained from hospital records. RESULTS:
      Among the 15 patients with neurological involvement, four cases (3 male, 1
      female) of acute TM associated with BD were confirmed. TM associated with BD
      affected cervical and thoracic levels of the spinal cord. Myelitis involved
      multiple segments (4 cases). TM developed at any stage of the disease, even as a
      dramatic initial presentation, leading to the diagnosis of BD (1 case). The
      longest time elapsed since the diagnosis of BD prior to the development of TM was
      10 years. A major association was the history of panuveitis in all four cases.
      Cyclophosphamide and steroid therapy were the mainstay of the treatment once the
      TM had developed. Treatment outcomes were variable, depending mostly on the
      severity of the neurologic involvement at presentation, timing of the initiation
      of the therapy and patients adherence with the treatment. Two of 4 cases
      recovered without major sequela. CONCLUSIONS: Although rare, the presented
      association and its detailed clinical discussions would serve to enhance our
      understanding of both TM and the spectrum of neurologic complications that BD may
      harbour. Early recognition and initiation of therapy are crucial for successful
      outcome.

PMID- 23558022
TI  - Progress in Biophysics and Molecular Biology. Can biology create a profoundly new
      mathematics and computation? Special theme issue on integral biomathics.
      Editorial.

PMID- 23558021
TI  - Effect of human urine on the tensile strength of sutures used for hypospadias
      surgery.
AB  - INTRODUCTION: Hypospadias is the most common congenital condition affecting
      between 1 in 250 and 300 live births. Even in experienced hands, surgery to
      repair this congenital defect can have a high complication rate. Wound dehiscence
      is reported to occur in 5% and fistula formation in 6%-40% depending on
      technique. The choice of suture material has been shown to affect the
      complication rate although there is (currently) no consensus about the best
      suture material to use. Ideally, the sutures used for urethroplasty should be
      absorbable while maintaining sufficient mechanical strength to support the wounds
      until they are self-supporting and able to resist urinary flow. Previous studies
      have compared the effects of human urine on different suture materials especially
      catgut. However, catgut is now banned in Europe. Our study examined the tensile
      and breaking strength as well as rate of degradation for four types of absorbable
      suture now commonly used for hypospadias repairs in the UK. MATERIAL AND METHODS:
      We examined the effect of prolonged storage (up to 27 days) in human urine on 6/0
      gauge Vicryl, Vicryl Rapide, Monocryl and polydioxanone (PDS) sutures. These four
      suture materials are commonly used by the senior plastic consultant surgeon (NK)
      for hypospadias repairs. 50 mm sections of these suture materials were stored in
      either urine or saline as control. At specified time points, each suture was
      placed in a uniaxial load testing machine to assess the stress-strain profile and
      the mechanical load required to break the suture was measured. KEY RESULTS:
      Exposure to urine reduced the tensile and breaking strength of all the suture
      materials tested. PDS demonstrated the greatest resilience. Vicryl Rapide was the
      weakest suture and degraded completely by day 6. Vicryl and Monocryl had similar
      degradation profiles, but Vicryl retained more of its tensile strength for
      longer. CONCLUSIONS: There is a balance to be struck between the duration that a
      suture material must remain in any surgical wound and the risk that it causes
      foreign body effects. The results of this study suggest that Vicryl has the best
      characteristics for urethroplasty of the four suture materials tested.

PMID- 23558023
TI  - Recurrent hydatid cyst: ultrasound detection of an unusual cardiac embolic
      source.

PMID- 23558024
TI  - Managing pulmonary arterial hypertension and optimizing treatment options:
      prognosis of pulmonary artery hypertension.
AB  - Survival in patients with pulmonary artery hypertension has improved, but
      outcomes are still suboptimal. Therapeutic focus must shift from short-term
      functional changes to improvements in long-term outcomes. Several outcome
      predictors, both at baseline and on therapy, offer guidance for clinicians
      treating pulmonary artery hypertension.

PMID- 23558025
TI  - Combination therapy in pulmonary arterial hypertension.
AB  - Many potential therapeutic options are now available for patients with pulmonary
      arterial hypertension. Interest has emerged in using therapies in various
      combinations. Retrospective experience has suggested that this approach is common
      and can be efficacious. Data are emerging supporting the benefit of combination
      therapy; however, limitations and questions remain about this strategy. This
      report reviewed the rationale for combination therapy and summarized the results
      from clinical trials.

PMID- 23558026
TI  - Managing pulmonary arterial hypertension and optimizing treatment options.
      Introduction.

PMID- 23558027
TI  - When to initiate intravenous therapy and/or refer.
AB  - Intravenous (IV) prostacyclin (epoprostanol) and its analogs (iloprost and
      treprostinil) are effective in treating pulmonary artery hypertension (PAH).
      Although prostacyclins are available for inhaled and subcutaneous delivery, IV
      administration of prostacyclins, sometimes in combination with other agents, such
      as bosentan or sildenafil, is considered the most aggressive method to manage
      PAH. This report attempts to help clinicians determine when to initiate IV
      treatment of PAH and when to refer a patient with PAH to a center for treatment.
      IV prostacyclin therapy initiation is suggested when patients exhibit World
      Health Organization functional class IV symptoms. The Registry to EValuate Early
      And Long-term Pulmonary Arterial Hypertension disease management (REVEAL) risk
      calculator can help determine a patient's 1-year mortality with PAH and
      characterize the clinical course, treatment, and predictors of outcomes in
      patients with PAH. Referring physicians can screen their patients for PAH and
      refer even before the diagnosis has been confirmed so that the center can
      facilitate the diagnostic process and provide suggestions for initial therapy
      selection and provide other collaborative and supportive services. Alternatively,
      the physician can diagnose and initiate early therapy with a plan to involve the
      pulmonary hypertension center at the need for IV therapy or consideration for
      transplantation, working closely with the patient to ensure stability. Physicians
      and pulmonary centers must develop good methods of communication to ensure
      effective diagnosis and management.

PMID- 23558028
TI  - Properly diagnosing pulmonary arterial hypertension.
AB  - Pulmonary hypertension (PH) is found in many clinical conditions and is
      associated with increased morbidity and mortality. Pulmonary arterial
      hypertension (PAH) is a clinical condition characterized by precapillary PH
      without causes such as lung disease, chronic thromboembolic PH, or other rare
      conditions. Evaluating a patient with suspected PH requires a series of
      investigations intended to confirm the diagnosis, determine the clinical PH group
      (and, in the case of PAH group 1, the specific etiology), and evaluate the
      functional and hemodynamic impairment. The workup should identify the risk
      factors for PH (e.g., left heart disease, lung diseases associated with alveolar
      hypoxia, and chronic thromboembolism) versus the conditions associated with PAH
      group 1 (e.g., scleroderma, human immunodeficiency virus, anorexigen use, liver
      disease). A detailed algorithm is presented to help physicians determine the
      appropriate PH category. Because the presence of one condition associated with PH
      does not exclude another etiologies, clinicians are strongly encouraged to follow
      the entire algorithm. Discussions and case studies are presented describing the
      differentiation of PAH group 1 from PH group 2 and PAH group 1 from PH group 3;
      diagnosing PH group 4; determining the long-term calcium channel blocker response
      in those with idiopathic PAH; and determining the severity of PH.

PMID- 23558029
TI  - MRI-compatible pipeline for three-dimensional MALDI imaging mass spectrometry
      using PAXgene fixation.
AB  - MALDI imaging mass spectrometry (MALDI-imaging) has emerged as a spatially
      resolved label-free bioanalytical technique for direct analysis of biological
      samples and was recently introduced for analysis of 3D tissue specimens. We
      present a new experimental and computational pipeline for molecular analysis of
      tissue specimens which integrates 3D MALDI-imaging, magnetic resonance imaging
      (MRI), and histological staining and microscopy, and evaluate the pipeline by
      applying it to analysis of a mouse kidney. To ensure sample integrity and
      reproducible sectioning, we utilized the PAXgene fixation and paraffin embedding
      and proved its compatibility with MRI. Altogether, 122 serial sections of the
      kidney were analyzed using MALDI-imaging, resulting in a 3D dataset of 200GB
      comprised of 2million spectra. We show that elastic image registration better
      compensates for local distortions of tissue sections. The computational analysis
      of 3D MALDI-imaging data was performed using our spatial segmentation pipeline
      which determines regions of distinct molecular composition and finds m/z-values
      co-localized with these regions. For facilitated interpretation of 3D
      distribution of ions, we evaluated isosurfaces providing simplified
      visualization. We present the data in a multimodal fashion combining 3D MALDI
      imaging with the MRI volume rendering and with light microscopic images of
      histologically stained sections. BIOLOGICAL SIGNIFICANCE: Our novel experimental
      and computational pipeline for 3D MALDI-imaging can be applied to address
      clinical questions such as proteomic analysis of the tumor morphologic
      heterogeneity. Examining the protein distribution as well as the drug
      distribution throughout an entire tumor using our pipeline will facilitate
      understanding of the molecular mechanisms of carcinogenesis.

PMID- 23558030
TI  - Exoproteome dynamics in Leishmania infantum.
AB  - The exoproteome of Leishmania infantum is composed of parasite derived proteins
      present in the extracellular environment. Although the exoproteome might have a
      significant role in the precocious steps of infection little is known concerning
      its composition. We developed an approach enabling the in vitro recovery of the
      exoproteome from logarithmic and stationary L. infantum promastigotes. The
      recovered exoproteomes were further separated into two fractions, vesicles and
      vesicle depleted exoproteome, evaluating the fraction protein profile. Although
      the most abundant protein in all fractions was GP63, the protein composition of
      the separated fractions was distinct reflecting the origin of the fraction and
      the metabolic state of the parasites. The vesicle-derived exoproteome recovered
      from logarithmic parasites was significantly enriched in ribosomal proteins,
      indicating a potential role for these vesicles in protein turnover. Also, a stage
      specific enrichment of vesicles with properties related to apoptotic vesicles was
      observed in stationary phase parasites and evidence was obtained that the release
      of vesicles was increased in response to a death stimuli. This report on the
      exoproteome obtained from in vitro promastigote cultures provides new
      perspectives on Leishmania biology with the possibility of vesicles playing a
      major role in protein turnover and also in cell death. BIOLOGICAL SIGNIFICANCE:
      The first systematic insight into Leishmania exoproteome composition and the
      impact of the selected recovery approach.

PMID- 23558032
TI  - Blastic plasmacytoid dendritic cell neoplasm in a human T-cell lymphotropic virus
      type I (HTLV-1) carrier: a coincidental association?

PMID- 23558031
TI  - p38 inhibition and not MK2 inhibition enhances the secretion of chemokines from
      TNF-alpha activated rheumatoid arthritis fibroblast-like synoviocytes.
AB  - OBJECTIVES: For many years the p38 MAP kinase (MAPK) has been a major anti
      inflammatory target for the development of an oral therapy for rheumatoid
      arthritis (RA). However, disappointing results from Phase II clinical studies
      suggest that adaptations may occur, which allow escape from blockade of the p38
      pathway. In this study we investigated whether p38 inhibition mediated JNK
      activation represents such an escape mechanism. METHODS: Interaction between the
      JNK and p38 pathways was studied in TNF-alpha stimulated THP-1 monocytes, primary
      macrophages and fibroblast-like synoviocytes from OA and RA patients using
      pharmacological inhibitors and siRNAs. RESULTS: TNF-alpha induced phosphorylation
      of JNK and c-Jun was sustained by p38 inhibitors in monocytes, primary
      macrophages and FLS. Upregulation of Mip1alpha, Mip1beta and IL-8 mRNAs and
      protein were observed upon p38 inhibition. More importantly, inhibition of MK2,
      the substrate of p38 did not sustain JNK activation upon TNF-alpha activation and
      did not elevate Mip1alpha, Mip1beta and IL-8 chemokines as compared to TNF-alpha
      alone. In this study, TNF-alpha or IL-1beta induced JNK activation is sustained
      by p38 inhibition, resulting in enhanced chemokine secretion. CONCLUSIONS: Based
      on the suggested role of these chemokines in RA pathogenesis, the upregulation of
      these chemokines may provide an explanation for the lack of efficacy of p38
      inhibitors in Phase II. The absence of any effect of MK2 inhibition in our models
      on this mechanism, while coming with similar efficacy on blocking p38, provides
      support for further investigations to reveal the potential of MK2 inhibition as a
      novel treatment of RA.

PMID- 23558033
TI  - Evaluation of a wild white-tailed deer population management program for
      controlling chronic wasting disease in Illinois, 2003-2008.
AB  - We evaluated population management programs for controlling chronic wasting
      disease (CWD) in wild white-tailed deer in Illinois between November 2002 and
      March 2008. The intervention consisted of measures of deer removal from three
      deer population control programs: Illinois Department of Natural Resources
      culling, deer population control permits and nuisance deer removal permits. We
      included in the analysis a total of 14,650 white-tailed deer CWD test results.
      These data also included location and demographic data collected from both deer
      harvested in the interventions as well as deer from hunter harvests and deer
      vehicle collisions. We quantified intervention pressures as the number of years
      of intervention, the total number of deer removed and the average number of deer
      removed per year. We accounted for temporal and spatial variations of
      intervention by using mixed logistic regression to model the association between
      intervention pressures and CWD prevalence change. The results showed that deer
      population management intervention as practiced in Illinois during the study
      period was negatively associated with CWD prevalence and the strength of
      association varied depending on age of deer and the measure of intervention
      pressure. The population management programs showed a more consistent association
      with reduced CWD prevalence in fawn and yearling white-tailed deer than in adult
      deer. Our results also suggested that frequent and continuing intervention events
      with at least moderate intensity of culling were needed to reduce CWD prevalence.
      A longer study period, however, is needed to make a more definite conclusion
      about the effectiveness of similar population management programs for controlling
      CWD in wild white-tailed deer.

PMID- 23558034
TI  - Photodegradation of cobalamins in aqueous solutions and in human blood.
AB  - Vitamin B12 (cobalamin) is required for proper red blood cell formation,
      neurologic function, and DNA synthesis. Cobalamins in solutions are light
      sensitive, but no comprehensive study has been performed to compare the
      photostability of different cobalamins under UVA exposure. Their indirect
      photodegradation due to their antioxidant properties and their photostability in
      vivo have also not been studied so far. The photodegradation of four cobalamins
      (methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), hydroxocobalamin (OHCbl) and
      cyanocobalamin (CNCbl)) under UVA exposure in aqueous solutions (pH=7.4) have
      been investigated by absorption spectroscopy. The photodegradation of OHCbl in
      the absence and presence of the endogenous photosensitizer riboflavin was
      studied. Serum vitamin B12 concentrations before and after summer were measured
      in four patients with psoriasis. All studied cobalamins are photolabile. The
      biologically active forms of cobalamin, AdCbl and MeCbl, are converted to OHCbl
      within seconds during UVA exposure. OHCbl is the most stable cobalamin. However,
      reactive oxygen species increases the degradation rate of OHCbl. Our pilot study
      on humans demonstrates that serum vitamin B12 concentrations are not
      significantly affected during summertime in Norway. Further work is needed to
      determine vitamin B12 photostability in humans living at lower latitudes or using
      sunbeds.

PMID- 23558035
TI  - Chloroquine pretreatment inhibits toll-like receptor 3 signaling after stroke.
AB  - Toll-like receptors (TLRs) mediated signaling is mainly implicated in
      inflammatory activation which contributes to the initiation and progression of
      stroke. Using a model of transient global cerebral ischemia (tGCI) in rats, we
      investigated the changes of pro-inflammation mediators and tested the effects of
      Chloroquine pretreatment on the expression of pro-inflammation mediators after
      stroke. Adult Male Sprague-Dawley (SD) rats were subjected to transient global
      cerebral ischemia (tGCI) and treated without or with Chiloquin pretreatment
      (60mg/kg) 2h before tGCI. Short-term spatial memory capacity, Western blot assay
      and semi-quantitive RT-PCR were performed. Compared to sham operated rats, tGCI
      rats showed worsened learning and memory capacity and increased expression of
      TLR3, interferon regulatory factor 3 (IRF3), and interferon beta (IFN-beta) in
      the Hippocampus after stroke. Chloroquine pretreatment significantly enhanced
      rats' short-term spatial memory capacity and attenuated the expression of TLR3,
      IFR3, and IFN-beta in the Hippocampus compared to non-treatment control in tGCI
      rats. Therefore, Chloroquine pretreatment of stroke inhibits inflammatory
      response and improves short-term spatial memory capacity. The TLR3/IFR3-IFN-beta
      signaling pathway may contribute to the reduced inflammatory response after
      stroke. Chloroquine warrants further investigation as a therapeutic agent for the
      treatment of stroke. 

PMID- 23558036
TI  - An accurate binding interaction model in de novo computational protein design of
      interactions: if you build it, they will bind.
AB  - Computational protein design efforts aim to create novel proteins and functions
      in an automated manner and, in the process, these efforts shed light on the
      factors shaping natural proteins. The focus of these efforts has progressed from
      the interior of proteins to their surface and the design of functions, such as
      binding or catalysis. Here we examine progress in the development of robust
      methods for the computational design of non-natural interactions between proteins
      and molecular targets such as other proteins or small molecules. This problem is
      referred to as the de novo computational design of interactions. Recent
      successful efforts in de novo enzyme design and the de novo design of protein
      protein interactions open a path towards solving this problem. We examine the
      common themes in these efforts, and review recent studies aimed at understanding
      the nature of successes and failures in the de novo computational design of
      interactions. While several approaches culminated in success, the use of a well
      defined structural model for a specific binding interaction in particular has
      emerged as a key strategy for a successful design, and is therefore reviewed with
      special consideration. 

PMID- 23558038
TI  - Early puberty and childhood social and behavioral adjustment.
AB  - PURPOSE: Early puberty has been linked to higher rates of mental health problems
      in adolescence. However, previous studies commencing after the initiation of
      puberty have been unable to explore whether early puberty is preceded by higher
      rates of these problems. In a large national study, we aimed to determine whether
      difficulties in behavior and psychosocial adjustment are evident before as well
      as during the early pubertal transition. METHODS: The Longitudinal Study of
      Australian Children recruited a nationally representative cohort of 4,983
      children at age 4-5 years in 2004. This analysis includes 3,491 of these children
      (70.1%) followed up at ages 6-7, 8-9, and 10-11 years, with a completed parent
      report of stage of pubertal maturation at age 8-9 years. Parents reported
      behavior difficulties (Strengths and Difficulties Questionnaire) and psychosocial
      adjustment (Pediatric Quality of Life Inventory) at all four waves from ages 4-5
      to 10-11 years. RESULTS: Both boys and girls who entered puberty early (i.e., by
      age 8-9 years) also experienced poorer psychosocial adjustment at this age. These
      psychosocial differences were already evident at ages 4-5 and 6-7 years, and
      persisted to at least age 10-11 years. Similar patterns were evident for behavior
      difficulties, but only for boys; early puberty was not related to behavior
      difficulties in girls. CONCLUSIONS: Children with early puberty have different
      patterns of behavior and social adjustment from the preschool years through early
      adolescence. At least in part, the association between early-onset puberty and
      poor mental health appears to result from processes under way well before the
      onset of puberty.

PMID- 23558039
TI  - Sexual function in patients with chronic angina pectoris.
AB  - Drugs for erectile dysfunction (ED) may be contraindicated with nitrates commonly
      used to treat patients with angina pectoris, and certain antianginal therapies
      may worsen ED. The American Heart Association and the Princeton Consensus
      Conference panel of experts recommend that patients with coronary artery disease
      and ED who experience angina pectoris undergo full medical evaluations to assess
      the cardiovascular risks associated with resuming sexual activity before being
      prescribed therapy for ED. Current antianginal therapies include beta blockers,
      calcium channel blockers, short- and long-acting nitrates, and ranolazine, a late
      sodium current inhibitor. Short- and long-acting nitrates remain a
      contraindication with phosphodiesterase-5 inhibitors commonly used to treat
      patients with ED, and the benefits of the other antianginal therapies must be
      weighed against their effects on cardiovascular health and erectile function. In
      conclusion, patients with coronary artery disease and ED who wish to initiate
      phosphodiesterase-5 inhibitor therapy and need to discontinue nitrate therapy
      need treatment options that manage their angina pectoris effectively, maintain
      their cardiovascular health, and provide the freedom to maintain their sexual
      function.

PMID- 23558037
TI  - Protein design for pathway engineering.
AB  - Design and construction of biochemical pathways has increased the complexity of
      biosynthetically-produced compounds when compared to single enzyme biocatalysis.
      However, the coordination of multiple enzymes can introduce a complicated set of
      obstacles to overcome in order to achieve a high titer and yield of the desired
      compound. Metabolic engineering has made great strides in developing tools to
      optimize the flux through a target pathway, but the inherent characteristics of a
      particular enzyme within the pathway can still limit the productivity. Thus,
      judicious protein design is critical for metabolic and pathway engineering. This
      review will describe various strategies and examples of applying protein design
      to pathway engineering to optimize the flux through the pathway. The proteins can
      be engineered for altered substrate specificity/selectivity, increased catalytic
      activity, reduced mass transfer limitations through specific protein
      localization, and reduced substrate/product inhibition. Protein engineering can
      also be expanded to design biosensors to enable high through-put screening and to
      customize cell signaling networks. These strategies have successfully engineered
      pathways for significantly increased productivity of the desired product or in
      the production of novel compounds. 

PMID- 23558040
TI  - Relation between transient or persistent acute kidney injury and long-term
      mortality in patients with myocardial infarction.
AB  - Limited information is available regarding the impact of acute kidney injury
      (AKI) during hospitalization on clinical outcomes after myocardial infarction
      (MI), and the effect of transient kidney injury (KI) on long-term mortality has
      not been validated. We retrospectively analyzed 2,289 patients diagnosed with MI.
      AKI patients were classified into a transient KI group and a persistent KI group
      based on serum creatinine levels at discharge. The end point of the study was 3
      year mortality after MI. We included 2,110 patients of whom 237 patients (11%)
      developed AKI during hospitalization. Of these 237 patients, 154 (65%) had
      transient KI, and 83 (35%) had persistent KI. Multivariate analysis showed that
      age, left ventricular ejection fraction, estimated glomerular filtration rate on
      admission, and Killip class were significantly associated with developing AKI
      during hospitalization. The adjusted hazard ratios for 3-year mortality were 1.71
      (95% confidence interval: 1.08-2.70) for AKI patients with transient KI and 2.21
      (95% confidence interval: 1.34-3.64) for AKI patients with persistent KI,
      compared with no AKI. In conclusion, AKI was associated with an increased risk of
      death for patients who experienced MIs and survived during hospitalization.
      Although renal function had completely recovered in many AKI patients at
      discharge, these transient KI patients are also at a great risk of death after
      MI.

PMID- 23558041
TI  - Development and validation of a cardiovascular risk assessment model in patients
      with established coronary artery disease.
AB  - Appropriate risk stratification of patients with established, stable coronary
      artery disease could contribute to the prevention of recurrent cardiovascular
      events. The purpose of the present study was to develop and validate risk
      prediction models for various cardiovascular end points in the EURopean trial On
      reduction of cardiac events with Perindopril in stable coronary Artery disease
      (EUROPA) database, consisting of 12,218 patients with established coronary artery
      disease, with a median follow-up of 4.1 years. Cox proportional hazards models
      were used for model development. The end points examined were cardiovascular
      mortality, noncardiovascular mortality, nonfatal myocardial infarction, coronary
      artery bypass grafting, percutaneous coronary intervention, resuscitated cardiac
      arrest, and combinations of these end points. The performance measures included
      Nagelkerke's R2, time-dependent area under the receiver operating characteristic
      curves, and calibration plots. Backward selection resulted in a prediction model
      for cardiovascular mortality (464 events) containing age, current smoking,
      diabetes mellitus, total cholesterol, body mass index, previous myocardial
      infarction, history of congestive heart failure, peripheral vessel disease,
      previous revascularization, and previous stroke. The model performance was
      adequate for this end point, with a Nagelkerke R2 of 12%, and an area under the
      receiver operating characteristic curve of 0.73. However, the performance of
      models constructed for nonfatal and combined end points was considerably worse,
      with an area under the receiver operating characteristic curve of about 0.6. In
      conclusion, in patients with established coronary artery disease, the risk of
      cardiovascular mortality during longer term follow-up can be adequately predicted
      using the clinical characteristics available at baseline. However, the prediction
      of nonfatal outcomes, both separately and combined with fatal outcomes, poses
      major challenges for clinicians and model developers.

PMID- 23558042
TI  - Role of C-reactive protein in determining microvascular function in patients with
      non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary
      intervention.
AB  - The extent of coronary microvascular dysfunction might be related, not only to
      patient characteristics and procedural factors, but also to the inflammatory
      status. The aim of the present study was to examine a possible association
      between inflammation, as reflected by the serum C-reactive protein (CRP) levels,
      and the extent of baseline and post-percutaneous coronary intervention (PCI)
      coronary microvascular dysfunction in patients with non-ST-segment elevation
      acute coronary syndrome undergoing PCI. A total of 42 patients undergoing PCI for
      non-ST-segment elevation acute coronary syndrome were enrolled. Coronary
      microvascular resistance (MR) was determined in the territory of culprit artery
      using a Doppler probe- and a pressure sensor-equipped guidewire both before
      (taking the collateral blood into account) and after PCI. The periprocedural
      changes in MR were calculated. The CRP levels at admission were correlated with
      the pre-PCI MR (r = 0.498, p = 0.001), post-PCI MR (r = 0.429, p = 0.005), and
      periprocedural changes in MR (r = 0.785, p <0.001). On multivariate regression
      analysis, the only predictor of the pre-PCI (beta = 0.531, p = 0.002) and post
      PCI (beta = 0.471, p = 0.012) MR was the serum CRP concentration. Likewise, the
      periprocedural changes in MR was predicted by the serum CRP levels (beta = 0.677,
      p = 0.001) and the presence of angiographic thrombus (beta = -0.275, p = 0.02).
      In conclusion, these results have shown that the CRP level is related to
      increased coronary MR in the territory of the culprit lesion. This suggests that
      inflammatory processes might play a role in microvascular impairment in patients
      with non-ST-segment elevation acute coronary syndrome.

PMID- 23558043
TI  - Effects of ivabradine and ranolazine in patients with microvascular angina
      pectoris.
AB  - Patients with microvascular angina (MVA) often have persistence of symptoms
      despite full classical anti-ischemic therapy. In this study, we assessed the
      effect of ivabradine and ranolazine in MVA patients. We randomized 46 patients
      with stable MVA (effort angina, positive exercise stress test [EST], normal
      coronary angiography, coronary flow reserve <2.5), who had symptoms inadequately
      controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily),
      ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina
      Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after
      treatment. Coronary microvascular dilation in response to adenosine and to cold
      pressor test and peripheral endothelial function (by flow-mediated dilation) were
      also assessed. Both drugs improved SAQ items and EuroQoL scale compared with
      placebo (p <0.01 for all), with ranolazine showing some more significant effects
      compared with ivabradine, on some SAQ items and EuroQoL scale (p <0.05). Time to
      1-mm ST-segment depression and EST duration were improved by ranolazine compared
      with placebo. No effects on coronary microvascular function and on flow-mediated
      dilation were observed with drugs or placebo. In conclusion, ranolazine and
      ivabradine may have a therapeutic role in MVA patients with inadequate control of
      symptoms in combination with usual anti-ischemic therapy.

PMID- 23558044
TI  - Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC
      and 2011 ACCF/AHA/HRS recommendations): a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines.

PMID- 23558045
TI  - Intra-arch widths: a meta-analysis.
AB  - OBJECTIVE: To determine and compare the mean values of various intra-arch
      distances in Class I, Class II division 1 and Class II division 2 patients.
      MATERIALS AND METHODS: The search engines PubMed, Embrace and Cochrane were
      employed to select articles for further study, and the sample thereby selected
      comprised adult subjects with full permanent dentition, without missing teeth,
      malformations or previous orthodontic treatment. Only subjects from articles
      published during the last 10 years were included in the study. RESULTS: The
      search located a total of 628 articles regarding arch form. However, only eight
      articles were chosen for the study. We observed that: the distance between
      mandibular canines is smaller in Class I than in Class II division 1; mandibular
      inter-molar distance is similar in Class I and Class II division 1; maxillary
      inter-canine distance is similar in Class I, Class II division 2 and Class II
      division 1; maxillary inter-premolar width is greater in Class I than in Class II
      division 1; and that maxillary inter-molar width is similar in Class I and Class
      II division 2. CONCLUSIONS: No statistically significant differences in arch
      width were found between the different classes analysed (there are only slightly
      differences between classes), except in the case of mandibular inter-canine width
      (L3), which was smaller in Class I than in Class II,1, and maxillary inter
      premolar width (U4), which was smaller in Class II-I than in Class I.

PMID- 23558047
TI  - Improvement of a gas chromatographic method for the analysis of iminosugars and
      other bioactive carbohydrates.
AB  - The analysis of derivatised iminosugars and other bioactive low molecular weight
      carbohydrates present at low concentrations in different vegetable extracts
      (hyacinth, mulberry and buckwheat) required the improvement of a previously
      developed gas chromatographic method. Among the different parameters optimized,
      the temperature of the injection port, evaluated for the first time, resulted to
      be the most important. Thus, 240  degrees C was chosen as a tradeoff to achieve
      the required volatility, to avoid degradation and to provide symmetric peaks for
      bioactive carbohydrates highly retained such as glycosyl inositols. GC-MS
      operating under selective ion monitoring (SIM) acquisition mode and GC-FID
      provided limits of detection and quantitation for the target compounds of 0.2 and
      0.7 ng g(-1) and of 1 and 3 ng g(-1) on average, respectively. Therefore, both
      methodologies could be considered appropriate to extend the range of quantitation
      of these bioactives.

PMID- 23558048
TI  - Water-based gas purge microsyringe extraction coupled with liquid chromatography
      for determination of alkylphenols from sea food Laminaria japonica Aresh.
AB  - A novel organic solvent-free mode of gas purge microsyringe extraction, termed
      water-based gas purge microsyringe extraction, was developed. This technique can
      directly extract target compounds in wet samples without any drying process.
      Parameters affecting the extraction efficiency were investigated. Under optimal
      extraction conditions, the recoveries of alkylphenols were between 87.6 and
      105.8%, and reproducibility was between 5.2 and 12.1%. The technique was also
      used to determine six kinds of alkylphenols (APs) from samples of Laminaria
      japonica Aresh. The OP and NP were detected in all the samples, and
      concentrations ranged from 26.0 to 54.5ngg(-1) and 45.0-180.4ngg(-1),
      respectively. The 4-n-butylphenol was detected in only one sample and its
      concentration was very low. Other APs were not detected in L. japonica Aresh
      samples. The experimental results demonstrated that the technique is fast,
      simple, non-polluting, allows for quantitative extraction, and a drying process
      was not required for wet samples. Since only aqueous solution and a conventional
      microsyringe were used, this technique proved affordable, efficient, and
      convenient for the extraction of volatile and semivolatile ionizable compounds. 

PMID- 23558049
TI  - A perspective on radiosurgery: creativity, elegance, simplicity, and flexibility
      to change.

PMID- 23558050
TI  - An international assessment of ovarian cancer incidence and mortality.
AB  - OBJECTIVE: To assess and characterize the temporal variation in ovarian cancer
      incidence and mortality by age within countries in the Americas, Europe, Asia,
      and Oceania. METHODS/MATERIALS: Data from the National Cancer Institute's
      Surveillance, Epidemiology, and End Results Program in the United States (U.S.)
      were used to assess ovarian cancer incidence rates (1998-2008) and mortality
      rates, (1988-2007 for 12-month survival, 1988-2006 for 24-month survival, and
      1988-2003 for 60-month survival), stratified by age at diagnosis. Data from
      GLOBOCAN were used to calculate country-specific incidence rates for 2010 and
      2020 and case-fatality rates for 2010. RESULTS: A statistically significant
      decrease in Annual Percent Change (APC) of ovarian cancer incidence was observed
      in the U.S. for all women (-1.03%), among women who were diagnosed at <65 years
      of age (-1.09%) and among women who were diagnosed at >=65 years of age (-0.95%).
      There was a statistically significant increase in the observed APC for survival
      at 12-months (0.19%), 24-months (0.58%), and 60-months (0.72%) for all women;
      however, 5-year survival for advanced stage (III or IV) disease was low at less
      than 50% for women <65 years and less than 30% for women >=65 years. Global
      results showed a wide range in ovarian cancer incidence rates, with China
      exhibiting the lowest rates and the Russian Federation and the United Kingdom
      exhibiting the highest rates. CONCLUSIONS: Ovarian cancer survival has shown
      modest improvement from a statistical perspective in the U.S. However, it is
      difficult to ascertain how clinically relevant these improvements are at the
      population or patient level.

PMID- 23558051
TI  - Folate receptor alpha (FRA) expression remains unchanged in epithelial ovarian
      and endometrial cancer after chemotherapy.
AB  - OBJECTIVE: Based on its expression profile, folate receptor alpha (FRA) is an
      attractive candidate for targeted diagnostics and therapeutics. However,
      applicability of these agents in residual or recurrent disease could be
      influenced by chemotherapy. We evaluated whether chemotherapy modified FRA
      expression in non-mucinous epithelial ovarian (EOC) and endometrial carcinoma
      (EC). METHODS: FRA staining was evaluated by immunohistochemistry, using MAb
      26B3, in 81 patients (41 EOCs and 40 ECs) and 17 control tissues (5 benign
      ovarian cysts, 5 normal ovarian, and 7 normal endometrial tissues). Chemotherapy
      effect was evaluated in 42 patients (30 paired samples at primary and interval
      debulking surgery and 12 from primary and recurrent disease). FRA expression was
      assessed using a semi-quantitative staining algorithm, the M-score (range 0-50).
      RESULTS: Median difference in M-score between tumor and control samples was 27.5
      for EOC (95% CI 10.0 to 45.0) and 6.7 for EC (95% CI -6.7 to 21.7). Paired
      samples from both primary and interval debulking surgery did not differ in FRA
      expression in EOC (median difference of M-score between paired samples of 0.0
      [95% CI -2.6 to 2.6]). Recurrent EOC tumors reflected FRA status at diagnosis
      (median difference of M-score between paired samples of 3.3 [95% CI -7.0 to
      13.6]). CONCLUSIONS: This study shows no significant difference in FRA expression
      after chemotherapy, strengthening the rationale for FRA targeted diagnostics and
      therapeutics in FRA expressing tumors, whether newly diagnosed or at recurrence.

PMID- 23558052
TI  - Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer:
      primum non nocere.
AB  - OBJECTIVE: The objective of this study is to compare ovarian function and
      surgical outcomes between patients affected by benign uterine pathologies
      submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy and women
      in which standard TLH with adnexal preservation was performed. METHODS: We
      retrospectively compared data of 79 patients who underwent TLH plus bilateral
      salpingectomy (group A), with those of 79 women treated by standard TLH without
      adnexectomy (sTLH) (group B). Ovarian reserve modification, expressed as the
      difference between 3 months post-operative and pre-operative values of Anti
      Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Antral Follicle
      Count (AFC), mean ovarian diameters and Peak Systolic Velocity (PSV), was
      recorded for each patient. For each surgical procedure, operative time, variation
      of hemoglobin level (DeltaHb), postoperative hospital stay, postoperative return
      to normal activity, and complication rate were recorded as secondary outcomes.
      RESULTS: According to our post-hoc analysis, this equivalence study resulted to
      have a statistical power of 96.8%. Significant difference was not observed
      between groups with respect to DeltaAMH (p=0.35), DeltaFSH (p=0.15), DeltaAFC
      (p=0.09), Delta mean ovarian diameters (p=0.57) and DeltaPSV (p=0.61). In
      addition, secondary outcomes such as operative time (p=0.79), DeltaHb (p=0.41),
      postoperative hospital stay (p=0.16), postoperative return to normal activity
      (p=0.11) and complication rate also did not show any significant difference.
      CONCLUSIONS: The addition of bilateral salpingectomy to TLH for prevention of
      ovarian cancer in women who do not carry a BRCA1/2 mutations do not show negative
      effects on the ovarian function. In addition, no perioperative complications are
      related to the salpingectomy step in TLH.

PMID- 23558054
TI  - Ovarian surface epithelium as a source of ovarian cancers: unwarranted
      speculation or evidence-based hypothesis?
AB  - OBJECTIVES: There has been increasing evidence that high grade serous ovarian
      carcinomas (HGSOCs), the most common and most lethal of all ovarian cancers,
      originate in oviductal fimbriae and metastasize to the ovary. The alternate
      hypothesis, that ovarian carcinomas may originate within the ovarian stroma in
      inclusion cysts lined by ovarian surface epithelium (OSE), has been criticized
      and often dismissed on the basis of the OSE's embryonic origin, mesothelial
      phenotype, tissue-specific markers, questionable ability to undergo metaplasia,
      and the lack of identifiable precursor lesions. This review analyzes these
      criticisms and summarizes evidence indicating that OSE as a source of ovarian
      cancers cannot be ruled out. METHODS: The literature was reviewed and
      representative reports were chosen to evaluate the current criticisms of, and
      evidence in favor of, the OSE hypothesis. RESULTS: The close developmental
      relationship between the oviduct and OSE, both of which originate in the
      mesothelial coelomic epithelium, accounts for their capacity to produce similar
      tumors. Histopathologic and experimental data show that OSE does undergo serous
      metaplasia, and that transformation of pure OSE cultures produces aggressive
      neoplasms resembling high- and low-grade serous carcinomas, but never
      mesotheliomas. There is evidence of premalignant changes (e.g. p53 inactivation)
      in morphologically normal OSE and of rare but definitive dysplastic and early
      preinvasive lesions in OSE-lined inclusion cysts. Conclusions based on tissue
      specific markers to identify origins of inclusion cysts usually disregard the
      changes in differentiation occurring when OSE is displaced to the stroma. Lastly,
      an explanation is offered for the rare detection of precursor lesions in OSE
      lined cysts, based on the likelihood that the duration from initiation of
      malignant transformation to invasive growth is minimal and thus difficult to
      detect. CONCLUSION: The likelihood that HGSOCs originate both in fimbriae and in
      OSE should be considered in clinical decisions involving choices between
      prophylactic salpingo-oophorectomies and salpingectomies.

PMID- 23558053
TI  - Predictors and costs of surgical site infections in patients with endometrial
      cancer.
AB  - OBJECTIVE: Technological advances in surgical management of endometrial cancer
      (EC) may allow for novel risk modification in surgical site infection (SSI).
      METHODS: Perioperative variables were abstracted from EC cases surgically staged
      between January 1, 1999, and December 31, 2008. Primary outcome was SSI, as
      defined by American College of Surgeons National Surgical Quality Improvement
      Program. Counseling and global models were built to assess perioperative
      predictors of superficial incisional SSI and organ/space SSI. Thirty-day cost of
      SSI was calculated. RESULTS: Among 1369 EC patients, 136 (9.9%) had SSI. In the
      counseling model, significant predictors of superficial incisional SSI were
      obesity, American Society of Anesthesiologists (ASA) score >2, preoperative
      anemia (hematocrit <36%), and laparotomy. In the global model, significant
      predictors of superficial incisional SSI were obesity, ASA score >2, smoking,
      laparotomy, and intraoperative transfusion. Counseling model predictors of
      organ/space SSI were older age, smoking, preoperative glucose >110 mg/dL, and
      prior methicillin-resistant Staphylococcus aureus (MRSA) infection. Global
      predictors of organ/space SSI were older age, smoking, vascular disease, prior
      MRSA infection, greater estimated blood loss, and lymphadenectomy or bowel
      resection. SSI resulted in a $5447 median increase in 30-day cost. CONCLUSIONS:
      Our findings are useful to individualize preoperative risk counseling.
      Hyperglycemia and smoking are modifiable, and minimally invasive surgical
      approaches should be the preferred surgical route because they decrease SSI
      events. Judicious use of lymphadenectomy may decrease SSI. Thirty-day
      postoperative costs are considerably increased when SSI occurs.

PMID- 23558055
TI  - Sjogren's syndrome and aromatase inhibitors treatment: is there a link?

PMID- 23558056
TI  - Age-related changes in executive control and their relationships with activity
      performance in handwriting.
AB  - Deterioration in the frontal and prefrontal cortex associated with executive
      functions (EF) occurs with age and may be associated with changes in daily
      performance. The aim of the present study was to describe changes occurring with
      age in Executive Functions (EF) and handwriting activity, as well as to analyze
      relationships between age, EF and handwriting performance. The study population
      included 80 healthy participants (aged 31 to 76+) living in the community. After
      answering five questions about their writing habits, the participants completed
      the Behavioral Assessment of the Dysexecutive Syndrome (BADS). In addition, they
      performed a handwriting task on a digitizer included in the Computerized
      Penmanship Evaluation Tool (ComPET), which provides kinematic measures of the
      handwriting process. Significant differences were found between the four age
      groups for both EF and temporal and spatial handwriting measures. A series of
      regressions indicated that age predicted 35% of the variance of the BADS profile
      score (EF control) and 32% of the variance of in-air time while writing. The
      results of this study indicated age effect on both EF control and handwriting
      performance. Possible implications for further research and clinical evaluation
      and intervention are discussed.

PMID- 23558057
TI  - The direction of bilateral transfer depends on the performance parameter.
AB  - To acquire a more comprehensive understanding of the learning benefits associated
      with bilateral transfer and to gain knowledge of possible mechanisms behind
      bilateral transfer, we investigated the transfer direction of several parameters
      which are assumed to represent important features of movement control in a visuo
      motor task. During the study, participants learned a multidirectional point-to
      point drawing task in which the visual feedback was rotated 45 degrees  and the
      gain was increased. Performance changes of the untrained hand in movement time,
      trajectory length, normalized jerk, initial direction error, ratio of the primary
      sub-movement time to the total movement time, and the accuracy of the aiming
      movement after the primary sub-movement were investigated as indices of learning
      from bilateral transfer. The results showed that performance parameters related
      to the initial production of the movement, such as the initial direction, ratio
      of primary sub-movement to the total movement time, and movement accuracy after
      the primary sub-movement, only transferred to the non-dominant, while hand
      performance variables related to the overall outcome, such as movement duration,
      movement smoothness, and trajectory length, transferred in both directions. The
      findings of the current study support the basic principle of the "dynamic
      dominance model" because it is suggested that overall improvements in the non
      dominant system are controlled by trajectory parameters in visuo-motor tasks,
      which resulted in transference of the afore mentioned production parameters to
      rather occur to the non-dominant hand as opposed to transference to the dominant
      hand. 

PMID- 23558058
TI  - Two molluscan BCL-2 family members from Manila clam, Ruditapes philippinarum:
      molecular characterization and immune responses.
AB  - Apoptosis based immune responses are important component of host defense in
      mollusks. In this study, we have identified two novel molluscan BCL-2 cDNAs from
      Manila clam, Ruditapes philippinarum and named as RpBCL-2A and RpBCL-2B. There
      were four and three highly conserved BCL-2 homology (BH) regions in RpBCL-2A and
      RpBCL-2B, respectively suggesting these two genes could be different isoforms of
      anti-apoptotic BCL-2 family. Phylogenetic results revealed that Manila clam BCL-2
      genes were clustered closely with invertebrate BCL-2 members. It gives evidence
      of their common origin and conserved features of invertebrate BCL-2 family. RpBCL
      2A and 2B were expressed in tissue-specific manner showing the highest and lowest
      level of expression in gills and hemocytes, respectively. However there was no
      clear expression profile difference between two genes. After Vibrio tapetis
      challenge, transcriptional responses of RpBCL-2A and RpBCL-2B were induced in
      gills and hemocytes with high variation that could be due to effects of immune
      reactions of other host defense molecules.

PMID- 23558059
TI  - Human serum albumin isoforms: genetic and molecular aspects and functional
      consequences.
AB  - BACKGROUND: At present, 67 different genetic variants of human serum albumin and
      proalbumin have been molecularly characterized at the protein and/or gene level.
      SCOPE OF REVIEW: This review summarizes present knowledge about genetic and
      molecular aspects, functional consequences and potential uses of the variants.
      MAJOR CONCLUSIONS: The frequency of bisalbuminemia in the general population is
      probably about 1:1000, but it can be much higher in isolated populations.
      Mutations are often due to hypermutable CpG dinucleotides, and in addition to
      single-amino acid substitutions, glycosylated variants and C-terminally modified
      alloalbumins have been found. Some mutants show altered stability in vivo and/or
      in vitro. High-affinity binding of Ni(++) and Cu(++) is blocked, or almost so, by
      amino acid changes at the N-terminus. In contrast, substitution of Leu90 and
      Arg242 leads to strong binding of triiodothyronine and l-thyroxine, respectively,
      resulting in two clinically important syndromes. Variants often have modified
      plasma half-lives and organ uptakes when studied in mice. GENERAL SIGNIFICANCE:
      Because alloalbumins do not seem to be associated with disease, they can be used
      as markers of migration and provide a model for study of neutral molecular
      evolution. They can also give valuable molecular information about albumins
      binding sites, antioxidant and enzymatic properties, as well as stability.
      Mutants with increased affinity for endogenous or exogenous ligands could be
      therapeutically relevant as antidotes, both for in vivo and extracorporeal
      treatment. Variants with modified biodistribution could be used for drug
      targeting. In most cases, the desired function can be further elaborated by
      producing site-directed, recombinant mutants. This article is part of a Special
      Issue entitled Serum Albumin.

PMID- 23558060
TI  - Detection of oxidized and glycated proteins in clinical samples using mass
      spectrometry--a user's perspective.
AB  - BACKGROUND: Proteins in human tissues and body fluids continually undergo
      spontaneous oxidation and glycation reactions forming low levels of oxidation and
      glycation adduct residues. Proteolysis of oxidised and glycated proteins releases
      oxidised and glycated amino acids which, if they cannot be repaired, are excreted
      in urine. SCOPE OF REVIEW: In this review we give a brief background to the
      classification, formation and processing of oxidised and glycated proteins in the
      clinical setting. We then describe the application of stable isotopic dilution
      analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS) for
      measurement of oxidative and glycation damage to proteins in clinical studies,
      sources of error in pre-analytic processing, corroboration with other techniques 
      including how this may be improved - and a systems approach to protein damage
      analysis for improved surety of analyte estimations. MAJOR CONCLUSIONS: Stable
      isotopic dilution analysis LC-MS/MS provides a robust reference method for
      measurement of protein oxidation and glycation adducts. Optimised pre-analytic
      processing of samples and LC-MS/MS analysis procedures are required to achieve
      this. GENERAL SIGNIFICANCE: Quantitative measurement of protein oxidation and
      glycation adducts provides information on level of exposure to potentially
      damaging protein modifications, protein inactivation in ageing and disease,
      metabolic control, protein turnover, renal function and other aspects of body
      function. Reliable and clinically assessable analysis is required for translation
      of measurement to clinical diagnostic use. Stable isotopic dilution analysis LC
      MS/MS provides a "gold standard" approach and reference methodology to which
      other higher throughput methods such as immunoassay and indirect methods are
      preferably corroborated by researchers and those commercialising diagnostic kits
      and reagents. This article is part of a Special Issue entitled Current methods to
      study reactive oxygen species - pros and cons and biophysics of membrane
      proteins. Guest Editor: Christine Winterbourn.

PMID- 23558061
TI  - Pharmacokinetic interactions between lersivirine and zidovudine, tenofovir
      disoproxil fumarate/emtricitabine and abacavir/lamivudine.
AB  - BACKGROUND: To investigate pharmacokinetic interactions associated with
      coadministration of lersivirine with zidovudine, tenofovir disoproxil fumarate
      (DF)/emtricitabine (Truvada((r))) or abacavir/lamivudine
      (Epzicom((r))/Kivexa((r))). METHODS: Three Phase I, open, crossover studies with
      two (studies 1 and 3) or three (study 2) treatment periods were conducted in
      healthy individuals. In study 1, individuals received zidovudine and placebo or
      zidovudine and lersivirine on days 1-14. In study 2, individuals received
      lersivirine and tenofovir DF/emtricitabine, lersivirine and placebo or tenofovir
      DF/emtricitabine and placebo on days 1-10. In study 3, individuals received
      abacavir/lamivudine only in period 1 (5 days) and abacavir/lamivudine and
      lersivirine in period 2 (10 days). Blood samples were taken on days 1-14 (study
      1) or day of final dose (studies 2 and 3) and analysed using high performance
      liquid chromatography/dual mass spectrometry. Pharmacokinetic parameters were
      calculated by standard non-compartmental methods. RESULTS: When coadministered
      with lersivirine, zidovudine exposure increased by 35%, and exposure of its
      metabolite zidovudine-glucuronide decreased by 19%. Following coadministration of
      lersivirine and tenofovir DF/emtricitabine, tenofovir exposure increased by 30%,
      and lersivirine exposure decreased by 12%. Coadministration of lersivirine and
      abacavir/lamivudine increased abacavir exposure by 27% and decreased lamivudine
      exposure by 8%. Adverse events were predominantly mild in these Phase I studies.
      CONCLUSIONS: Coadministration of lersivirine with zidovudine, tenofovir
      DF/emtricitabine or abacavir/lamivudine influenced the systemic exposure of all
      nucleoside reverse transcriptase inhibitor agents investigated (except for
      lamivudine; emtricitabine pharmacokinetics were not assessed). Changes were not
      considered clinically meaningful for zidovudine and abacavir. The clinical
      relevance of the effect on tenofovir pharmacokinetics is currently unknown.

PMID- 23558062
TI  - A descriptive study of myoclonus associated with etomidate procedural sedation in
      the ED.
AB  - BACKGROUND: Myoclonus is a well-recognized side effect of etomidate when given in
      induction doses for rapid sequence intubation. Most of the data reported on
      myoclonus with emergency department (ED) sedation doses are reported as a
      secondary finding. STUDY OBJECTIVES: Our objective was to prospectively quantify
      the incidence and duration of myoclonus associated with the administration of
      etomidate in the lower doses given for procedural sedation in the ED. METHODS:
      This was a prospective descriptive study performed between September 2008 and
      September 2010 at an urban teaching hospital ED with approximately 50000 patient
      visits per year. Procedural sedation was performed at the discretion of the
      treating emergency physician, and adult patients receiving etomidate were
      eligible for enrollment. The occurrence and duration of myoclonus were observed
      and recorded. Any interference of myoclonus with the ability to complete the
      procedure was recorded, and adverse effects were identified. RESULTS: Thirty-four
      eligible subjects were enrolled, and 36 separate sedation procedures were
      performed. The mean initial etomidate dose was 0.13 mg/kg (range, 0.077-0.20),
      and the mean total etomidate dose was 0.15 mg/kg (range, 0.077-0.29). Myoclonus
      was noted in 26 (72%) of 36 sedations. Mean time to onset of myoclonus was 50
      seconds (range, 15-146), and the mean duration was 93 seconds (range, 03-557).
      Myoclonus interfered with the procedure in only 1 (3%) of 36 attempted
      procedures, and no procedure was unsuccessful because of myoclonus. CONCLUSION:
      Myoclonus associated with sedation doses of etomidate was common but rarely
      interfered with the completion of a procedure.

PMID- 23558063
TI  - Inappropriate use of qualitative, point-of-care urine human chorionic
      gonadotropin test.

PMID- 23558064
TI  - Subspecialty radiology and surgery.

PMID- 23558065
TI  - Therapeutic approaches to non-alcoholic fatty liver disease: past achievements
      and future challenges.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of
      chronic liver injury and mortality in Western countries and China. However, as to
      date, there is no direct and effective therapy for this disease. The aim of this
      review is to analyze the key progress and challenges of main current therapeutic
      approaches in NAFLD. DATA SOURCE: We carried out a PubMed search of English
      language articles relevant to NAFLD therapy. RESULTS: There are two major
      therapeutic strategies for NAFLD treatment: (1) lifestyle interventions
      (including weight reduction, dietary modification and physical exercise) and (2)
      pharmaceutical therapies. Lifestyle interventions, particularly chronic and
      moderate intensity exercise, are the most effective and recognized clinical
      therapies for NAFLD. For pharmaceutical therapies, although their effects and
      mechanisms have been extensively investigated in laboratory studies, they still
      need further tests and investigations in clinical human trials. CONCLUSION:
      Future advancement of NAFLD therapy should focus on the mechanistic studies on
      cell based and animal models and human clinical trials of exercise, as well as
      the combination of lifestyle intervention and pharmaceutical therapy specifically
      targeting main signaling pathways related to lipid metabolism, oxidative stress
      and inflammation.

PMID- 23558066
TI  - Stepwise approach and surgery for gallbladder adenomyomatosis: a mini-review.
AB  - BACKGROUND: Gallbladder adenomyomatosis (GBA) is a hyperplastic disease affecting
      the wall of the gallbladder, with some typical features. It has historically been
      considered a benign condition, nevertheless recent reports highlighted a
      potential role of GBA in predisposing to malignancies of the gallbladder. DATA
      SOURCES: We reviewed the literature concerning GBA from its identification until
      July 2012. Owing to the relative rarity of the disease, studies often are case
      reports or case series. Thus we herein report a summary of the key-points
      concerning diagnosis and treatment of GBA, easily applicable in everyday
      practice, rather than a systematic review. Also, results are integrated with our
      recent experience. RESULTS: In our experience, we observed a trend toward an
      increase of GBA during the last years, probably due to enhanced ultrasonographic
      technical advancements and physician's expertise. GBA has distinctive imaging
      features. Several recent reports highlight the potential risk of cancer
      associated with GBA; however the disease is still classified as a benign
      condition. Although its correlation with malignancy has not been demonstrated, it
      is prudent to recommend cholecystectomy in some cases. However, in selected
      asymptomatic patients, a wait-and-see policy is a viable alternative. We propose
      an algorithm, based on GBA pathological pattern (diffuse, segmental, localized or
      fundal), suitable for decision-making. CONCLUSIONS: In symptomatic patients and
      if the diagnosis is doubtful, cholecystectomy is mandatory. Postponing surgery is
      an option to be offered to asymptomatic patients with low-risk GBA pattern who
      adhere to scheduled follow-ups.

PMID- 23558067
TI  - Outcomes in children with biliary atresia following liver transplantation.
AB  - BACKGROUND: Congenital biliary atresia is a rare condition characterized by
      idiopathic dysgenesis of the bile ducts. If untreated, congenital biliary atresia
      leads to liver cirrhosis, liver failure and premature death. The present study
      aimed to evaluate the outcomes of orthotopic liver transplantation in children
      with biliary atresia. METHOD: We retrospectively analyzed 45 patients with
      biliary atresia who had undergone orthotopic liver transplantation from September
      2006 to August 2012. RESULTS: The median age of the patients was 11.0 months (5
      102). Of the 45 patients, 41 were younger than 3 years old. Their median weight
      was 9.0 kg (4.5-29.0), 34 of the 45 patients were less than 10 kg. Thirty-one
      patients had undergone Kasai portoenterostomy prior to orthotopic liver
      transplantation. We performed 30 living donor liver transplants and 15 split
      liver transplants. Six patients died during a follow-up. The median follow-up
      time of surviving patients was 11.4 months (1.4-73.7). The overall 1-, 2- and 3
      year survival rates were 88.9%, 84.4% and 84.4%, respectively. CONCLUSION: With
      advances in surgical techniques and management, children with biliary atresia
      after liver transplantation can achieve satisfactory survival in China, although
      there remains a high risk of complications in the early postoperative period.

PMID- 23558068
TI  - HBV recurrence lowered by lamivudine/HBIG combination therapy in liver transplant
      patients: ten-year experience.
AB  - BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to
      treat patients with hepatitis B recurrence after liver transplantation. However,
      the outcomes are inconclusive. The present study was undertaken to evaluate the
      effect of combined therapy on patients with hepatitis B recurrence after liver
      transplantation. METHODS: Twenty-two patients with hepatitis B recurrence after
      liver transplantation from August 2000 to October 2011 were enrolled in this
      study. Of these patients, 16 received lamivudine plus HBIG (combination therapy
      group) and 6 were treated with lamivudine alone (lamivudine-treated group). The
      clinical features were matched in the two groups. HBV recurrence parameters,
      HBsAg clearance rate, patient survival rate, and survival time were compared.
      RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant
      difference was noted in the HBsAg clearance rate in the lamivudine-treated and
      combination therapy groups (50% vs 93.8%, P<0.05). There was no significant
      difference in the time of HBV recurrence, patient survival rate and survival time
      between lamivudine-treated and combination therapy groups (P>0.05). CONCLUSION:
      Compared with lamivudine monotherapy, combination therapy significantly increased
      the HBsAg clearance rate in patients with HBV recurrence after liver
      transplantation.

PMID- 23558070
TI  - Management hepatolithiasis with operative choledochoscopic FREDDY laser
      lithotripsy combined with or without hepatectomy.
AB  - BACKGROUND: Hepatolithiasis is very common in East Asia. It is benign in nature,
      but has a high recurrence rate. It is likely to lead to biliary cirrhosis and
      increase the risk of cholangiocarcinoma. Hence, the treatment of hepatolithiasis
      is difficult but vital. In this report, we present a novel approach to manage
      hepatolithiasis using the choledochoscopic Frequency-Doubled Double pulse Nd:YAG
      (FREDDY) laser lithotripsy combined with or without hepatectomy. METHODS: Between
      July 2009 and October 2012, 45 patients underwent choledochoscopic FREDDY laser
      lithotripsy combined with or without hepatectomy (laser lithotripsy group). Forty
      eight patients underwent a traditional operation (traditional method group) from
      January 2009 to June 2009. Comparative analysis was made of demographic and
      clinical characteristics of the two groups. RESULTS: The final stone clearance
      rate of the laser lithotripsy group was 93.3%, whereas that of the traditional
      method group was 85.4% (P=0.22). In the laser lithotripsy group, 2 patients
      experienced hemobilia and 3 patients had acute cholangitis. In the traditional
      method group, 3 patients had intraoperative hemorrhage, 1 patient had bile
      leakage, 6 patients had acute cholangitis, and 1 patient died of liver failure.
      Moreover, the operative time in the traditional method group was significantly
      longer than that in the laser lithotripsy group (P=0.01). The mean hospital stay
      of the patients in the traditional method group was longer than that in the laser
      lithotripsy group (9.8 vs 8.2 days, P=0.17). Recurrent intrahepatic bile duct
      stones were not found during the follow-up period in the two groups. CONCLUSION:
      Operative choledochoscopic FREDDY laser lithotripsy combined with or without
      hepatectomy may be an effective and safe treatment for hepatolithiasis.

PMID- 23558069
TI  - Short-term entecavir versus lamivudine therapy for HBeAg-negative patients with
      acute-on-chronic hepatitis B liver failure.
AB  - BACKGROUND: Selection of drugs for antiviral therapy of patients with hepatitis B
      virus (HBV)-related acute-on-chronic liver failure (ACLF) remains difficult. This
      study was undertaken to evaluate the short-term efficacy of entecavir versus
      lamivudine on hepatitis B e antigen (HBeAg)-negative patients with ACLF. METHODS:
      The data of 182 HBeAg-negative patients with ACLF were retrospectively collected
      from patient profiles of the hospital. In these patients, 93 HBeAg-negative
      patients with ACLF were treated orally with 0.5 mg of entecavir and 89 were
      treated orally with 100 mg of lamivudine every day. The gender and age were
      matched between the two groups. Biochemical items, the model for end-stage liver
      disease (MELD) score, and HBV DNA level were matched at baseline between the two
      groups and monitored during treatment. The 3-month mortalities of the two groups
      were compared. RESULTS: No significant differences were found in biochemical
      items, MELD score, and HBV DNA level at baseline (P>0.05). HBV DNA level
      decreased within 3 months in both groups (P<0.05), regardless of the pretreatment
      MELD score. In patients with the same range of pretreatment MELD scores,
      treatment duration, posttreatment HBV DNA levels, percentage of HBV DNA level
      <2.7 lg copies/mL, biochemical items, MELD scores and 3-month mortality were
      similar in the two groups (all P>0.05). Pretreatment MELD score was not related
      to posttreatment HBV DNA levels (P>0.05), but related to a 3-month mortality in
      both groups (both P<0.001). CONCLUSIONS: In HBeAg-negative patients with ACLF,
      the short-term efficacy of entecavir versus lamivudine was similar. The degree of
      pretreatment liver failure significantly affected the outcome of treatment.

PMID- 23558071
TI  - Application of acoustic radiation force impulse imaging for the evaluation of
      focal liver lesion elasticity.
AB  - BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is a new elastography
      method for the evaluation of tissue stiffness. This study aims to evaluate the
      performance of ARFI in noninvasive assessment of the tissue stiffness of focal
      liver lesion (FLL) and to explore its potential value in the differential
      diagnosis of FLL. METHODS: ARFI was performed in 140 patients with 154 FLLs,
      which included 28 hemangiomas (ANGIs), 14 focal nodular hyperplasias (FNHs), 61
      hepatocellular carcinomas (HCCs), 39 metastases and 12 cholangiocellular
      carcinomas (CCCs). Virtual touch tissue quantification (VTTQ) values were
      obtained, analyzed and compared. The area under the receiver operating
      characteristic curve (AUROC) and optimal cut-off values were obtained using a
      receiver operating characteristic (ROC) curve analysis to assess diagnostic
      performance. All cases were definitively diagnosed using histopathology, CT, MRI
      or contrast-enhanced ultrasound. RESULTS: The VTTQ median values of ANGI, FNH,
      HCC, metastasis and CCC were 1.30, 1.80, 2.52, 3.08 and 3.89 m/s, respectively. A
      significant increase in the VTTQ values of different lesions was observed:
      ANGI<FNH<HCC<InvalidTagstasis<CCC (P<0.001). The AUROC (95% CI) of VTTQ values
      was 0.94 (0.90-0.98) for ANGI, 0.91 (0.87-0.96) for malignant lesions and 0.87
      (0.79-0.94) for CCC. The sensitivity and specificity for ANGI (86.5%, 89.3%,
      respectively), malignancy (81.3%, 92.9%, respectively), and CCC (91.7%, 72.5%,
      respectively) were associated with VTTQ cut-off values of 1.76, 2.22 and 3.00
      m/s, respectively. CONCLUSIONS: ARFI can accurately and objectively assess the
      elasticity of lesions by obtaining the shear wave elastic value of FLL with VTTQ.
      Therefore, ARFI is a novel, simple, noninvasive and useful diagnostic method for
      the characterization of FLL.

PMID- 23558072
TI  - Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early
      diagnosis is of the utmost importance. This study aimed to investigate the values
      of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription
      for diagnosis and monitoring of metastasis of HCC. METHODS: Liver GPC-3 was
      analyzed in HCC tissues from 36 patients by immunohistochemistry and Western
      blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123
      HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified
      by RT-PCR, quantitative real-time PCR, and confirmed by DNA sequencing.
      Circulating GPC-3 level was detected by ELISA. RESULTS: The increasing expression
      of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule
      like staining localized in tumor parts of atypical hyperplasia and HCC formation.
      The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous
      tissues, and none in distal cancerous tissues (P<0.001), with no significant
      difference in differentiation grade and tumor number except for size (Z=2.941,
      P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference
      was found between GPC-3 and tumor size (X2=6.318, P=0.012) or HBV infection
      (X2=23.362, P<0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC
      tissues, with relation to TNM stage, periportal cancerous embolus, and extra
      hepatic metastasis (P<0.001). The combination of circulating GPC-3, GPC-3 mRNA
      and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%).
      CONCLUSION: Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as
      markers for the diagnosis of HCC and monitoring its metastasis.

PMID- 23558073
TI  - Ethyl pyruvate prevents inflammatory factors release and decreases intestinal
      permeability in rats with D-galactosamine-induced acute liver failure.
AB  - BACKGROUND: The pathogenesis and progression of acute liver failure (ALF) are
      closely associated with intestinal endotoxemia because of the high permeability
      of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to
      protect liver failure effectively. The current study aimed to explore the
      relationship between proinflammatory cytokines and intestinal permeability, and
      to investigate whether EP administration might prevent the release of multiple
      proinflammatory cytokines and decrease intestinal permeability and therefore,
      protect the liver from injury. METHODS: The ALF model was induced by D
      galactosamine in rats. The rats were randomly divided into control (saline,
      i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40
      mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2
      hours after D-galactosamine). Samples were obtained at 12 and 24 hours after ALF
      induction, respectively. The histology of liver and intestinal tissue was
      assessed. Serum alanine aminotransferase, endotoxin, D(-)-lactate, diamine
      oxidase (DAO), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats
      was also recorded. RESULTS: The rats in model group showed severe damage to liver
      tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP
      significantly improved liver or intestinal injury. In addition, serum endotoxin,
      D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels were significantly
      increased in the model group compared with the control group. There was a
      positive correlation between intestinal permeability and proinflammatory
      cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF
      alpha, IFN-gamma and HMGB1 levels. The median survival time was significantly
      prolonged in both prevention and treatment groups (126 and 120 hours compared
      with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic
      effects on intestinal mucosa. EP decreases intestinal permeability, and inhibits
      the release of multiple proinflammatory cytokines in rats with ALF.

PMID- 23558074
TI  - Correlation of S1P1 and ERp29 expression to progression, metastasis, and poor
      prognosis of gallbladder adenocarcinoma.
AB  - BACKGROUND: Gallbladder cancer (GBC) is one of the most aggressive malignant
      neoplasms with an extremely poor prognosis. Early diagnosis significantly
      increases the survival rate. The present study was undertaken to evaluate the
      diagnostic and prognostic value of sphingosine-1-phosphate receptor 1 (S1P1) and
      endoplasmic reticulum protein 29 (ERp29) in benign and malignant gallbladder
      lesions and to develop a possible alternative treatment for GBC. METHODS: A total
      of 100 gallbladder adenocarcinoma, 46 peritumoral, 30 gallbladder adenomatous, 15
      gallbladder polyp, and 35 chronic cholecystitis tissues were included. S1P1 and
      ERp29 expressions were evaluated by immunohistochemistry. The correlation between
      S1P1 and ERp29 expression and tumor pathological features and prognosis was
      analyzed. RESULTS: S1P1 positive rate was significantly higher in gallbladder
      adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic
      cholecystitis tissues. On the contrary, ERp29 positive rate was significantly
      lower in adenocarcinomas than that in peritumoral, adenomatous, polyp, and
      chronic cholecystitis tissues. Benign lesions with positive S1P1 or negative
      ERp29 expression showed moderate or severe atypical hyperplasia in the
      gallbladder epithelium. The overexpression of S1P1 or non-expression of ERp29 was
      significantly associated with tumor differentiation, tumor mass, lymph node
      metastasis, and adenocarcinoma invasion. Univariate Kaplan-Meier analysis showed
      that the elevated S1P1 (P=0.008) or absence of ERp29 (P=0.043) was closely
      associated with decreased survival rate. Multivariate Cox regression analysis
      showed that S1P1 positive (P=0.004) or ERp29 negative (P=0.029) was an
      independent predictor of poor prognosis in gallbladder adenocarcinoma.
      CONCLUSION: S1P1 overexpression or ERp29 absence is related to the carcinogenesis
      and progression, and may be potential biomarkers for early detection of
      gallbladder adenocarcinoma.

PMID- 23558075
TI  - Pancreaticoduodenectomy: a comparison of superior approach with classical
      Whipple's technique.
AB  - BACKGROUND: Pancreaticoduodenectomy (PD) is the standard procedure for resecting
      tumors arising from the periampullary area and the pancreatic head. Nevertheless
      this procedure is inherently difficult and associated with high morbidity and
      mortality. Besides, the technique applied for exposing the portal and superior
      mesenteric veins is time-consuming, difficult and associated with the risk of
      major venous injury. Recently we have introduced a modified approach for making
      this part of the procedure quick, safe and bloodless, which constitutes the
      subject of this study. METHODS: Patients who underwent pylorus preserving
      pancreaticoduodenectomy (PPPD) either by superior approach technique (group 1) or
      by classical Whipple's technique (group 2) were retrospectively identified. Age
      sex composition, body mass index (BMI), total operative time, operative blood
      loss, intraoperative blood transfusion requirement, morbidity, mortality and
      length of hospital stay were compared between the two groups. RESULTS: Between
      January 1997 and December 2011, 72 patients underwent PPPD by the superior
      approach technique (group 1) and 38 underwent PPPD by the classical Whipple's
      technique (group 2) at our institution. Statistically significant differences
      were observed in operative time (208.1+/-46.3 minutes in group 1 vs 322.0+/-33.8
      minutes in group 2), operative blood loss (601.0+/-250.3 mL in group 1 vs
      1371.5+/-471.8 mL in group 2), and intraoperative blood transfusion requirement
      [10 (13.9%) patients in group 1 and 24 (63.2%) in group 2]. Among 18 (16.4%)
      obese patients, significant differences in operative time, operative blood loss
      and intraoperative blood transfusion requirement were observed between groups 1
      and 2. There was no significant inter-group difference in complication rate among
      obese patients, but comparing obese patients with normal weight patients revealed
      higher rates of complications like pancreatic fistula (27.8% vs 6.5%), delayed
      gastric emptying (16.7% vs 5.4%), and infective complications like wound
      infection and intra abdominal collection (44.4% vs 5.4%). CONCLUSIONS: On the
      basis of analytical data, we conclude that the superior approach technique is
      effective for PD compared with the classical Whipple's technique. It allows fast,
      safe and virtually bloodless dissection for exposure of the superior mesenteric
      and portal veins during early steps of PD. PD is normally a difficult and tedious
      procedure carrying a remote risk of major venous injury leading to substantial
      blood loss.

PMID- 23558076
TI  - Decreased expression of DAB2IP in pancreatic cancer with wild-type KRAS.
AB  - BACKGROUND: KRAS mutation plays an important role in the pathogenesis of
      pancreatic cancer. However, the role of wild-type KRAS in the progression of
      pancreatic cancer remains unknown. The present study was to investigate the
      expression of the Ras GTPase activating protein (DAB2IP) in pancreatic cancer and
      its clinical significance. METHODS: The expression of DAB2IP in pancreatic cancer
      cell lines and normal human pancreatic ductal epithelial cells was analyzed by
      Western blotting and real-time quantitative reverse transcription-PCR (qRT-PCR).
      The KRAS mutational types of pancreatic cancer tissues obtained from pancreatic
      cancer patients (n=20) were also analyzed. Subsequently, DAB2IP expression was
      detected in pancreatic cancer tissues, adjacent and normal pancreatic tissues
      (n=2) by immunohistochemistry, and the relationship between DAB2IP expression and
      the clinical characteristics of patients was evaluated. RESULTS: Western blotting
      and qRT-PCR results showed that DAB2IP expression in pancreatic cancer cells with
      wild-type KRAS was lower than that in those with mutation-type KRAS and normal
      human pancreatic ductal epithelial cells (P<0.05). Immunohistochemistry showed
      that DAB2IP expression was lower in pancreatic cancer tissues than that in
      adjacent and normal pancreatic tissues (Z=-4.000, P=0.000). DAB2IP expression was
      lower in pancreatic cancer patients with the wild-type KRAS gene than that in
      those with KRAS mutations (WilcoxonW=35.000, P=0.042). Furthermore, DAB2IP
      expression in patients with perineurial invasion was lower than that in those
      without invasion (WilcoxonW=71.500, P=0.028). DAB2IP expression was lower in
      patients with more advanced stage than that in those with early clinical stage
      (WilcoxonW=54.000, P=0.002). CONCLUSIONS: DAB2IP expression was reduced in
      patients with pancreatic cancer compared with those with no cancer. DAB2IP
      expression was correlated with the KRAS gene, perineurial invasion and clinical
      stage of the disease. Our data indicated that DAP2IP expression can be used as a
      potential prognostic indicator and a promising molecular target for therapeutic
      intervention in patients with pancreatic cancer.

PMID- 23558077
TI  - Hepaticojejunostomy with the "Hand-Fan" technique.
AB  - A standard hepaticojejunostomy technique might be difficult to perform,
      especially when the bile duct is small and located deep in the liver hilum.
      Herein we present a new procedure, the Hand-Fan technique, that was used to
      enhance the exposure and ease the performance of these challenging anastomoses.
      Thirty-one patients who had had hepaticojejunostomy with this technique for bile
      duct injury and other benign biliary pathologies from July 2004 to June 2011 were
      included into the study. Median postoperative hospital stay was 7 days (6-25
      days) and median follow-up time was 33 months (2-84 months). Liver function tests
      revealed that the blood bilirubin levels of the patients were normalized after
      hepaticojejunostomy. Follow-up showed that there were no signs of clinical
      recurrence or impaired bile flow. The Hand-Fan technique considerably facilitates
      challenging hepaticojejunostomies. Surgeon's comfort is exceptional and the
      clinical results are satisfactory.

PMID- 23558078
TI  - Risk factors of choledocholithiasis formation after liver transplantation.
AB  - Systematic study of risk factors for biliary stone post-liver transplantation is
      rarely performed. To investigate the risk factor of choledocholithiasis formation
      after liver transplantation, we conducted a case-control study. Fourteen patients
      were selected into a study group. The stones of the bile duct of the patients
      were confirmed and treated successfully by endoscopic retrograde
      cholangiopancreatography. For univariate analysis, we selected carefully some
      potential risk factors such as cold ischemia time, warm ischemia time, and
      biliary stricture. The results revealed that cold ischemia time and biliary
      stenosis were significant predictors. But multivariate analysis revealed that
      only biliary stenosis was a significant risk factor. In conclusion, biliary
      stenosis is a risk factor of bile duct stones formation after liver
      transplantation. Endoscopic retrograde cholangiopancreatography is effective and
      safe in the diagnosis or treatment of bile duct stones after liver
      transplantation.

PMID- 23558079
TI  - Technical note on complete excision of choledochal cysts.
AB  - BACKGROUND: Choledochal cysts are congenital cystic dilatations of the
      extrahepatic or intrahepatic portion of the biliary tree. Complete excision of
      choledochal cysts is currently regarded as the gold standard treatment, while
      less extensive procedures including cystoduodenostomy have become obsolete due to
      the potential for malignant change in the remnant cyst. For type-1 choledochal
      cysts, which sometimes extend to the main pancreatic duct closely, some surgeons
      may adopt a less aggressive approach in order to avoid damage to the main
      pancreatic duct as such damage can lead to serious consequences. However,
      incomplete excision of choledochal cysts may also cause problems. METHOD: Here we
      report on a reoperation treating incomplete excision of a choledochal cyst with
      focus on the technical aspect. RESULTS: In the reoperation, meticulous dissection
      of the liver hilum which had been previously operated on was performed. The
      hepaticojejunostomy was left intact. With the assistance of intraoperative
      cholangiography, the residual pancreatic portion of the choledochal cyst was
      completely excised. The pancreatic opening and the lower end of the common bile
      duct were reconstructed. Whipple operation was avoided. CONCLUSION: Careful
      planning with the aid of precise imaging before and during the operation largely
      enhanced the accuracy of the excision of the choledochal cyst.

PMID- 23558080
TI  - Effect of a foot-drop stimulator and ankle-foot orthosis on walking performance
      after stroke: a multicenter randomized controlled trial.
AB  - BACKGROUND: Studies have demonstrated the efficacy of functional electrical
      stimulation in the management of foot drop after stroke. OBJECTIVE: To compare
      changes in walking performance with the WalkAide (WA) foot-drop stimulator and a
      conventional ankle-foot orthosis (AFO). METHODS: Individuals with stroke within
      the previous 12 months and residual foot drop were enrolled in a multicenter,
      randomized controlled, crossover trial. Subjects were assigned to 1 of 3 parallel
      arms for 12 weeks (6 weeks/device): arm 1 (WA-AFO), n = 38; arm 2 (AFO-WA), n =
      31; arm 3 (AFO-AFO), n = 24. Primary outcomes were walking speed and
      Physiological Cost Index for the Figure-of-8 walking test. Secondary measures
      included 10-m walking speed and perceived safety during this test, general
      mobility, and device preference for arms 1 and 2 for continued use. Walking tests
      were performed with (On) and without a device (Off) at 0, 3, 6, 9, and 12 weeks.
      RESULTS: Both WA and AFO had significant orthotic (On-Off difference),
      therapeutic (change over time when Off), and combined (change over time On vs
      baseline Off) effects on walking speed. An AFO also had a significant orthotic
      effect on Physiological Cost Index. The WA had a higher, but not significantly
      different therapeutic effect on speed than an AFO, whereas an AFO had a greater
      orthotic effect than the WA (significant at 12 weeks). Combined effects on speed
      after 6 weeks did not differ between devices. Users felt as safe with the WA as
      with an AFO, but significantly more users preferred the WA. CONCLUSIONS: Both
      devices produce equivalent functional gains.

PMID- 23558081
TI  - Study of the thermodynamics of chromium(III) and chromium(VI) binding to
      iron(II/III)oxide or magnetite or ferrite and magnanese(II) iron (III) oxide or
      jacobsite or manganese ferrite nanoparticles.
AB  - Removal of chromium(III) or (VI) from aqueous solution was achieved using Fe3O4,
      and MnFe2O4 nanomaterials. The nanomaterials were synthesized using a
      precipitation method and characterized using XRD. The size of the nanomaterials
      was determined to be 22.4+/-0.9 nm (Fe3O4) and 15.5+/-0.5 nm (MnFe2O4). The
      optimal binding pH for chromium(III) and chromium(VI) were pH 6 and pH 3.
      Isotherm studies were performed, under light and dark conditions, to determine
      the capacity of the nanomaterials. The capacities for the light studies with
      MnFe2O4 and Fe3O4 were determined to be 7.189 and 10.63 mg/g, respectively, for
      chromium(III). The capacities for the light studies with MnFe2O4 and Fe3O4 were
      3.21 and 3.46 mg/g, respectively, for chromium(VI). Under dark reaction
      conditions the binding of chromium(III) to the MnFe2O4 and Fe3O4 nanomaterials
      were 5.74 and 15.9 mg/g, respectively. The binding capacity for the binding of
      chromium(VI) to MnFe2O4 and Fe3O4 under dark reaction conditions were 3.87 and
      8.54 mg/g, respectively. The thermodynamics for the reactions showed negative
      DeltaG values, and positive DeltaH values. The DeltaS values were positive for
      the binding of chromium(III) and for chromium(VI) binding under dark reaction
      conditions. The DeltaS values for chromium(VI) binding under the light reaction
      conditions were determined to be negative.

PMID- 23558083
TI  - Unconscious task set priming with phonological and semantic tasks.
AB  - Whether unconscious stimuli can modulate the preparation of a cognitive task is
      still controversial. Using a backward masking paradigm, we investigated whether
      the modulation could be observed even if the prime was made unconscious in 100%
      of the trials. In two behavioral experiments, subjects were instructed to
      initiate a phonological or semantic task on an upcoming word, following an
      explicit instruction and an unconscious prime. When the SOA between prime and
      instruction was sufficiently long (84 ms), primes congruent with the task set
      instruction led to speedier responses than incongruent primes. In the other
      condition (36 ms), no task set priming was observed. Repetition priming had the
      opposite tendency, suggesting the observed task set facilitation cannot be
      ascribed solely to perceptual repetition priming. Our results therefore confirm
      that unconscious information can modulate cognitive control for currently active
      task sets, providing sufficient time is available before the conscious decision.

PMID- 23558082
TI  - The neuroinflammatory response of postoperative cognitive decline.
AB  - BACKGROUND: Aseptic surgical trauma provokes a homeostatic neuroinflammatory
      response to promote healing and protect the organism from further injury. When
      this response is dysregulated, harmful consequences can follow, including
      postoperative cognitive decline. SOURCES OF DATA: We performed a comprehensive
      search on PubMed related to postoperative cognitive dysfunction (POCD). AREAS OF
      AGREEMENT: Although the precise pathogenic mechanisms for POCD remain unclear,
      certain risk factors are known. AREAS OF CONTROVERSY: The mechanisms that lead to
      exaggerated and persistent neuroinflammation and the best way to counteract it
      are still unknown. AREAS FOR DEVELOPING RESEARCH: It is imperative that we
      identify the underlying processes that increase the risk of cognitive decline in
      elderly surgical patients. In this review we explore non-resolution of
      inflammation as an underlying cause of developing exaggerated and persistent
      POCD. If interventions can be developed to promote resolution of
      neuroinflammation, the patient's postoperative recovery will be enhanced and long
      term consequences can be prevented.

PMID- 23558084
TI  - A review of dark fermentative hydrogen production from biodegradable municipal
      waste fractions.
AB  - Hydrogen is believed to play a potentially key role in the implementation of
      sustainable energy production, particularly when it is produced from renewable
      sources and low energy-demanding processes. In the present paper an attempt was
      made at critically reviewing more than 80 recent publications, in order to
      harmonize and compare the available results from different studies on hydrogen
      production from FW and OFMSW through dark fermentation, and derive reliable
      information about process yield and stability in view of building related
      predictive models. The review was focused on the effect of factors, recognized as
      potentially affecting process evolution (including type of substrate and co
      substrate and relative ratio, type of inoculum, food/microorganisms [F/M] ratio,
      applied pre-treatment, reactor configuration, temperature and pH), on the
      fermentation yield and kinetics. Statistical analysis of literature data from
      batch experiments was also conducted, showing that the variables affecting the H2
      production yield were ranked in the order: type of co-substrate, type of pre
      treatment, operating pH, control of initial pH and fermentation temperature.
      However, due to the dispersion of data observed in some instances, the ambiguity
      about the presence of additional hidden variables cannot be resolved. The results
      from the analysis thus suggest that, for reliable predictive models of
      fermentative hydrogen production to be derived, a high level of consistency
      between data is strictly required, claiming for more systematic and comprehensive
      studies on the subject.

PMID- 23558085
TI  - Visuospatial working memory is impaired in an animal model of schizophrenia
      induced by acute MK-801: an effect of pretraining.
AB  - Deficient working memory was proposed as an endophenotype of schizophrenia. Such
      deficits are also commonly found in animal models of schizophrenia-like behavior
      of various origins. An allothetic place avoidance alternation task was proposed
      as a behavioral test of visuospatial working memory. This study tested the
      hypothesis that working memory in this test would be impaired by acute pre-test
      treatment with MK-801 (dizocilpine) in an animal model possessing high
      phenomenological and predictive validity. Furthermore, the study sought to
      determine the effect of pretraining to the task prior to treatment on the
      subsequent learning in the animal model. The results show that both doses of MK
      801 (0.12 mg/kg and 0.15 mg/kg) significantly impaired working memory in the
      alternation paradigm, and both doses also increased locomotor activity. Notably,
      in previously pretrained animals, the significant effect of MK-801 on working
      memory was absent, despite persistent hyperlocomotion. These results showed that
      a deficit in working memory was detectable in this animal model of schizophrenia
      like behavior, but its occurrence depended on the previous experience of animals
      with familiarization in the task.

PMID- 23558086
TI  - iPhone(r) applications as versatile video tracking tools to analyze behavior in
      zebrafish (Danio rerio).
AB  - Zebrafish (Danio rerio) are emerging as a promising model organism for
      experimental studies relevant to biological psychiatry. The objective of this
      study was to develop a novel video-based movement tracking and analysis system to
      quantify behavioral changes following psychoactive drug exposure in zebrafish. We
      assessed the effects of withdrawal from chronic ethanol exposure, and subsequent
      administration of fluoxetine (Prozac(r)), buspirone (Buspar(r)), and diazepam
      (Valium) using two behavioral paradigms; the Novel Tank Diving Test and the
      Light/Dark Choice Assay. A video tracking system was developed using two Apple(r)
      applications (Apps) to quantify these behaviors. Data from zebrafish exposed to
      the above treatments are presented in this paper not only to exemplify behavioral
      alterations associated with chronic exposure, but also more importantly, to
      validate the video tracking system. Following withdrawal from chronic ethanol
      exposure, zebrafish exhibited dose/time-dependent anxiogenic effects; including
      reduced exploration and freezing behavior in the Novel Tank Diving Test, and
      preference for the dark area for the Light/Dark Choice Assay. In contrast, the
      above drug treatments had significant anxiolytic effects. We have developed a
      simple and cost-effective method of measuring zebrafish behavioral responses. The
      iPhone(r) Apps outlined in this study offer numerous flexible methods of data
      acquisition; namely, ease of identification and tracking of multiple animals,
      tools for visualization of the tracks, and calculation of a range of analysis
      parameters. Furthermore, the limited amount of time required for interpretation
      of the video data makes this a powerful high-throughput tool with potential
      applications for pre-clinical drug development.

PMID- 23558087
TI  - This special Issue of Chemico-Biological Interactions comprises 70 manuscripts
      from lectures and short talks given at the 11th International Meeting on
      Cholinesterases. Preface.

PMID- 23558088
TI  - Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned
      mice.
AB  - L-DOPA alleviates the motor symptoms of Parkinson's disease, but its long-term
      use is associated with undesirable dyskinesia. We now tested whether exercise can
      attenuate this L-DOPA-induced dyskinesia (LID). We tested the effects of exercise
      on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. Animals were
      treated with L-DOPA/benserazide (25/12.5 mg/kg, i.p.) without and with
      possibility to exercise (running wheel) during 2 weeks. Exercise drastically
      prevented the development of LID, and its associated aberrant striatal signaling,
      namely the hyperphosphorylation of dopamine and cAMP-regulated phosphoprotein 32
      kDa protein and c-Fos expression. Our results indicate that exercise can
      partially prevent the development of LID through the normalization of
      striatopallidal dopaminergic signaling.

PMID- 23558089
TI  - The regulatory role of NF-kappaB in autophagy-like cell death after focal
      cerebral ischemia in mice.
AB  - Autophagy may contribute to ischemia-induced cell death in the brain, but the
      regulation of autophagic cell death is largely unknown. Nuclear factor kappa B
      (NF-kappaB) is a regulator of apoptosis in cerebral ischemia. We examined the
      hypothesis that autophagy-like cell death could contribute to ischemia-induced
      brain damage and the process was regulated by NF-kappaB. In adult wild-type (WT)
      and NF-kappaB p50 knockout (p50(-/-)) mice, focal ischemia in the barrel cortex
      was induced by ligation of distal branches of the middle cerebral artery. Twelve
      to 24h later, autophagic activity increased as indicated by enhanced expression
      of Beclin-1 and LC3 in the ischemic core and/or penumbra regions. This increased
      autophagy contributed to cell injury, evidenced by terminal
      deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)
      co-staining and a protective effect achieved by the autophagy inhibitor 3
      methyladenine. The number of Beclin-1/TUNEL-positive cells was significantly more
      in p50(-/-) mice than in WT mice. Neuronal and vascular cell death, as determined
      by TUNEL-positive cells co-staining with NeuN or Collagen IV, was more abundant
      in p50(-/-) mice. Immunostaining of the endothelial cell tight junction marker
      occludin revealed more damage to the blood-brain barrier in p50(-/-) mice.
      Western blotting of the peri-infarct tissue showed a reduction of Akt-the
      mammalian target of rapamycin (mTOR) signaling in p50(-/-) mice after ischemia.
      These findings provide the first evidence that cerebral ischemia induced
      autophagy-like injury is regulated by the NF-kappaB pathway, which may suggest
      potential treatments for ischemic stroke.

PMID- 23558090
TI  - Activation of both Group I and Group II metabotropic glutamatergic receptors
      suppress retinogeniculate transmission.
AB  - Relay cells of dorsal lateral geniculate nucleus (LGN) receive a Class 1
      glutamatergic input from the retina and a Class 2 input from cortical layer 6.
      Among the properties of Class 2 synapses is the ability to activate metabotropic
      glutamate receptors (mGluRs), and mGluR activation is known to affect
      thalamocortical transmission via regulating retinogeniculate and thalamocortical
      synapses. Using brain slices, we studied the effects of Group I
      (dihydroxyphenylglycine) and Group II ((2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl)glycine) mGluR agonists on retinogeniculate synapses. We
      showed that both agonists inhibit retinogeniculate excitatory postsynaptic
      currents (EPSCs) through presynaptic mechanisms, and their effects are additive
      and independent. We also found high-frequency stimulation of the layer 6
      corticothalamic input produced a similar suppression of retinogeniculate EPSCs,
      suggesting layer 6 projection to LGN as a plausible source of activating these
      presynaptic mGluRs.

PMID- 23558091
TI  - Effect of parathyroid hormone combined with gait training on bone density and
      bone architecture in people with chronic spinal cord injury.
AB  - OBJECTIVE: To evaluate the response of bone to 2 anabolic stimuli, teriparatide
      and mechanical loading, in subjects with spinal cord injury. DESIGN: A pilot
      study, 1 group, pretest-posttest. SETTING: A rehabilitation hospital.
      PARTICIPANTS: A convenience sample of 12 nonambulatory chronic spinal cord injury
      subjects. METHODS: The subjects were administered open-label teriparatide 20
      MUg/d while undergoing robotic-assisted stepping 3 times a week for 6 months,
      followed by 6 months of teriparatide alone. MAIN OUTCOME MEASUREMENTS: Bone
      status was evaluated at 3, 6, and 12 months by using dual-energy x-ray
      absorptiometry to calculate bone mineral density (BMD) at the spine and hip,
      magnetic resonance imaging to assess bone microarchitecture of the distal tibia,
      and serum bone markers. RESULTS: Mean (SD) baseline BMD measurements at the spine
      and the left and right total hip were 1.05 +/- 0.162 g/cm(2), 0.638 +/- 0.090
      g/cm(2) and 0.626 +/- 0.088 g/cm(2), respectively. After 6 months of treatment,
      BMD changed 2.19% +/- 3.61%, 0.02% +/- 2.21%, and 0.74% +/- 2.80% at the spine,
      and left and right total hip, respectively. These changes were not statistically
      significant (P > .05 for all). Magnetic resonance imaging supported an anabolic
      effect after 3 months of treatment with significant (P < .05) changes in
      trabecular thickness, 4.4% +/- 4.06%; surface-to-curve ratio, 23.6% +/- 22.3%;
      and erosion index, -17.04% +/- 12.9%. Although the trend remained after 6 months,
      statistical significance was not retained. At 6 months, bone markers indicated an
      increase in mean levels of bone-specific alkaline phosphatase, 53.8% +/- 62.9%; C
      terminal telopeptides of type I collagen, 137.6% +/- 194.6%; and intact amino
      terminal propeptide of type I procollagen, 61.4% +/- 99.3%. CONCLUSION: In this
      limited pilot study, teriparatide and mechanical loading resulted in a numerical
      but not statistically significant increase in lumbar spine BMD and no significant
      BMD changes at the hip. Magnetic resonance imaging at the distal tibia suggested
      an anabolic effect, but the high sensitivity offered by this technique was
      challenged by the limited ability to obtain analyzable data from all the
      subjects. Further studies that involve longer treatment periods and greater
      mechanical loading are warranted.

PMID- 23558092
TI  - Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behcet's
      disease.
AB  - OBJECTIVES: Oligoclonal bands (OCB) of immunoglobulins (IgG) in the cerebrospinal
      fluid (CSF) provides an evidence for the humoral response and have been screened
      in the CSF and serum of patients revealing 5 different patterns. In this study,
      patients with Behcet's disease (BD) are screened in a larger sample to
      potentially provide information about the possible role of CSF oligoclonal
      immunoglobulins in the diagnosis of this disease. METHODS: Paired CSF and serum
      samples from 121 consecutive BD patients with neurological complaints (43 women
      and 78 men) were included in this study. Parenchymal NBD was diagnosed in 74
      patients, and 22 patients had cerebral venous sinus thrombosis (CVST); of the
      remaining patients, 18 had primary headache disorders not directly associated
      with BD, and 7 had a cerebrovascular event. OCB of IgG were detected by
      isoelectric focusing on agarose and immunoblotting of matched serum and CSF
      sample pairs. Intrathecal production of IgG only is considered positive (Pattern
      2 or 3). RESULTS: In the whole group, only 8 patients had OCB in the CSF showing
      pattern 2. All these positive cases had parenchymal neuro-BD (10.8% positive and
      78.4% negative in parenchymal neuro-BD group). All other groups were negative.
      CONCLUSIONS: The rare presence of oligoclonal IgG bands in CSF can be utilized as
      another laboratory finding in the diagnosis of NBD.

PMID- 23558093
TI  - Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for
      treatment-naive HCV genotype 1: SOUND-C1 final results.
AB  - BACKGROUND: Faldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting
      antiviral agents under development for the treatment of chronic HCV infection.
      This article describes the final results of the Phase Ib SOUND-C1 study that
      evaluated the interferon-free oral combination of faldaprevir, deleobuvir and
      ribavirin in 32 treatment-naive patients infected with HCV genotype 1. METHODS:
      Patients were randomized to receive deleobuvir 400 mg (n=15) or 600 mg (n=17)
      three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin
      for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir
      plus pegylated interferon-alpha2a/ribavirin to week 24 or 48. RESULTS: At week 4,
      73% (11/15) and 100% (17/17) of patients in the deleobuvir 400 mg and 600 mg
      groups achieved HCV RNA<25 IU/ml, respectively. During interferon-free treatment,
      virological breakthrough was reported in one patient and re-increase of HCV RNA
      in one patient. Both patients were successfully treated with interferon
      containing therapy. The rate of sustained virological response 24 weeks after
      completion of treatment was 73% (11/15) in the deleobuvir 400 mg group and 94%
      (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon
      alpha2a/ribavirin treatment, the most common adverse events were pruritus (38% of
      patients), rash (31%) and asthenia (31%); these were severe in approximately 3%
      of patients. CONCLUSIONS: Potent antiviral activity and favourable safety of the
      treatment regimen were demonstrated. Furthermore, the results suggest that
      patients with breakthrough at week 4 may be rescued with an interferon-containing
      regimen. Clinical trials.gov number NCT01132313.

PMID- 23558095
TI  - Confounds in multivariate pattern analysis: Theory and rule representation case
      study.
AB  - Multivariate pattern analysis (MVPA) is a relatively recent innovation in
      functional magnetic resonance imaging (fMRI) methods. MVPA is increasingly widely
      used, as it is apparently more effective than classical general linear model
      analysis (GLMA) for detecting response patterns or representations that are
      distributed at a fine spatial scale. However, we demonstrate that widely used
      approaches to MVPA can systematically admit certain confounds that are
      appropriately eliminated by GLMA. Thus confounds rather than distributed
      representations may explain some cases in which MVPA produced positive results
      but GLMA did not. The issue is that it is common practice in MVPA to conduct
      group tests on single-subject summary statistics that discard the sign or
      direction of underlying effects, whereas GLMA group tests are conducted directly
      on single-subject effects themselves. We describe how this common MVPA practice
      undermines standard experiment design logic that is intended to control at the
      group level for certain types of confounds, such as time on task and individual
      differences. Furthermore, we note that a simple application of linear regression
      can restore experimental control when using MVPA in many situations. Finally, we
      present a case study with novel fMRI data in the domain of rule representations,
      or flexible stimulus-response mappings, which has seen several recent MVPA
      publications. In our new dataset, as with recent reports, standard MVPA appears
      to reveal rule representations in prefrontal cortex regions, whereas GLMA
      produces null results. However, controlling for a variable that is confounded
      with rule at the individual-subject level but not the group level (reaction time
      differences across rules) eliminates the MVPA results. This raises the question
      of whether recently reported results truly reflect rule representations, or
      rather the effects of confounds such as reaction time, difficulty, or other
      variables of no interest.

PMID- 23558094
TI  - The scent of salience--is there olfactory-trigeminal conditioning in humans?
AB  - Pavlovian fear conditioning has been thoroughly studied in the visual, auditory
      and somatosensory domain, but evidence is scarce with regard to the chemosensory
      modality. Under the assumption that Pavlovian conditioning relies on the supra
      modal mechanism of salience attribution, the present study was set out to attest
      the existence of chemosensory aversive conditioning in humans as a specific
      instance of salience attribution. fMRI was performed in 29 healthy subjects
      during a differential aversive conditioning paradigm. Two odors (rose, vanillin)
      served as conditioned stimuli (CS), one of which (CS+) was intermittently coupled
      with intranasally administered CO2. On the neural level, a robust differential
      response to the CS+ emerged in frontal, temporal, occipito-parietal and
      subcortical brain regions, including the amygdala. These changes were paralleled
      by the development of a CS+-specific connectivity profile of the anterior
      midcingulate cortex (aMCC), which is a key structure for processing salience
      information in order to guide adaptive response selection. Increased coupling
      could be found between key nodes of the salience network (anterior insula, neo
      cerebellum) and sensorimotor areas, representing putative input and output
      structures of the aMCC for exerting adaptive motor control. In contrast,
      behavioral and skin conductance responses did not show significant effects of
      conditioning, which has been attributed to contingency unawareness. These
      findings imply substantial similarities of conditioning involving chemosensory
      and other sensory modalities, and suggest that salience attribution and adaptive
      control represent a general, modality-independent principle underlying Pavlovian
      conditioning.

PMID- 23558096
TI  - Voxel-based morphometry and histological analysis for evaluating hippocampal
      damage in a rat model of cardiopulmonary resuscitation.
AB  - Cardiac arrest and subsequent cardiopulmonary resuscitation (CPR) induce
      hippocampal damage, which has been identified using histological analysis of post
      mortem brains. Voxel-based morphometry (VBM), an in-vivo assessment of regional
      differences in the concentration or volume of a particular tissue such as gray
      matter, has revealed CPR-induced decreases in gray matter in the hippocampus,
      where histopathological findings were observed. However, the potential link
      between the changes in gray matter detected by VBM and hippocampal damage has not
      been investigated directly. In this study, we compared results obtained using VBM
      directly to results from histological analyses in the same CPR rat brains, which
      exhibited neuronal loss and microglial invasion in the CA1 region of the
      hippocampus (CA1). T2-weighted images were obtained and preprocessed for VBM to
      produce gray matter concentration (GMC) maps in rats with asphyxia-induced
      cardiac arrest and CPR and sham-operated controls (n=12 each). Brains were fixed,
      and the number of neurons and microglia in CA1 were counted. VBM revealed a
      significant decrease in GMC in CPR rats compared to sham-operated controls. The
      CPR-induced decrease in GMC was localized to CA1, which is the same brain region
      where neuronal loss and microglial invasion were noted in response to CPR. GMC
      values were positively correlated with the number of neurons and tended to be
      negatively correlated with the number of microglia in CA1 of CPR rats. In
      conclusion, these results indicate that VBM-detected alterations in gray matter
      can be used as a surrogate marker for hippocampal damage following CPR.

PMID- 23558097
TI  - The parcellation-based connectome: limitations and extensions.
AB  - The human connectome is an intricate system of interconnected elements, providing
      the basis for integrative brain function. An essential step in the macroscopic
      mapping and examination of this network of structural and functional interactions
      is the subdivision of the brain into large-scale regions. Parcellation approaches
      used for the formation of macroscopic brain networks include application of
      predefined anatomical templates, randomly generated templates and voxel-based
      divisions. In this review, we discuss the use of such parcellation approaches for
      the examination of connectome characteristics. We specifically address the impact
      of the choice of parcellation scheme and resolution on the estimation of the
      brain's topological and spatial network features. Although organizational
      principles of functional and structural brain networks appear to be largely
      independent of the adopted parcellation approach, quantitative measures of these
      principles may be significantly modulated. Future parcellation-based connectome
      studies might benefit from the adoption of novel network tools and promising
      advances in connectivity-based parcellation approaches. 

PMID- 23558098
TI  - Synchronized electrical stimulation of the rat medial forebrain bundle and
      perforant pathway generates an additive BOLD response in the nucleus accumbens
      and prefrontal cortex.
AB  - To study how a synchronized activation of two independent pathways affects the
      fMRI response in a common targeted brain region, blood oxygen dependent (BOLD)
      signals were measured during electrical stimulation of the right medial forebrain
      bundle (MFB), the right perforant pathway (PP) and concurrent stimulation of the
      two fiber systems. Repetitive electrical stimulations of the MFB triggered
      significant positive BOLD responses in the nucleus accumbens (NAcc), septum,
      anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), ventral tegmental
      area/substantia nigra (VTA/SN), right entorhinal cortex (EC) and colliculus
      superior, which, in general, declined during later stimulation trains. At the
      same time, negative BOLD responses were observed in the striatum. Thus, the same
      stimulus caused region-specific hemodynamic responses. An identical electrical
      stimulation of the PP generated positive BOLD responses in the right dentate
      gyrus/hippocampus proper/subiculum (DG/HC), the right entorhinal cortex and the
      left entorhinal cortex, which remained almost stable during consecutive
      stimulation trains. Co-stimulation of the two fiber systems resulted in an
      additive activation pattern, i.e., the BOLD responses were stronger during the
      stimulation of the two pathways than during the stimulation of only one pathway.
      However, during the simultaneous stimulation of the two pathways, the development
      of the BOLD responses to consecutive trains changed. The BOLD responses in
      regions that were predominantly activated by MFB stimulation (i.e., NAcc, septum
      and ACC/mPFC) did not decline as fast as during pure MFB stimulation, thus an
      additive BOLD response was only observed during later trains. In contrast, in the
      brain regions that were predominantly activated by PP stimulation (i.e., right
      EC, DG/HC), co-stimulation of the MFB only resulted in an additive effect during
      early trains but not later trains. Consequently, the development of the BOLD
      responses during consecutive stimulations indicates the presence of an
      interaction between the two pathways in a target region, whereas the observed
      averaged BOLD responses do not.

PMID- 23558099
TI  - NIRS in clinical neurology - a 'promising' tool?
AB  - Near-infrared spectroscopy (NIRS) has become a relevant research tool in
      neuroscience. In special populations such as infants and for special tasks such
      as walking, NIRS has asserted itself as a low resolution functional imaging
      technique which profits from its ease of application, portability and the option
      to co-register other neurophysiological and behavioral data in a 'near natural'
      environment. For clinical use in neurology this translates into the option to
      provide a bed-side oximeter for the brain, broadly available at comparatively low
      costs. However, while some potential for routine brain monitoring during cardiac
      and vascular surgery and in neonatology has been established, NIRS is largely
      unknown to clinical neurologists. The article discusses some of the reasons for
      this lack of use in clinical neurology. Research using NIRS in three major
      neurologic diseases (cerebrovascular disease, epilepsy and headache) is reviewed.
      Additionally the potential to exploit the established position of NIRS as a
      functional imaging tool with regard to clinical questions such as preoperative
      functional assessment and neurorehabilitation is discussed. 

PMID- 23558101
TI  - Regional structural differences across functionally parcellated Brodmann areas of
      human primary somatosensory cortex.
AB  - Ultra-high-field (UHF) MRI is ideally suited for structural and functional
      imaging of the brain. High-resolution structural MRI can be used to map the
      anatomical boundaries between functional domains of the brain by identifying
      changes related to the pattern of myelination within cortical gray matter,
      opening up the possibility to study the relationship between functional domains
      and underlying structure in vivo. In a recent study, we demonstrated the
      correspondence between functional (based on retinotopic mapping) and structural
      (based on changes in T2(*)-weighted images linked to myelination) parcellations
      of the primary visual cortex (V1) in vivo at 7T (Sanchez-Panchuelo et al.,
      2012b). Here, we take advantage of the improved BOLD CNR and high spatial
      resolution achievable at 7T to study regional structural variations across the
      functionally defined areas within the primary somatosensory cortex (S1) in
      individual subjects. Using a traveling wave fMRI paradigm to map the internal
      somatotopic representation of the index, middle, and ring fingers in S1, we were
      able to identify multiple map reversals at the tip and base, corresponding to the
      boundaries between Brodmann areas 3a, 3b, 1 and 2. Based on high resolution
      structural MRI data acquired in the same subjects, we inspected these
      functionally-parcellated Brodmann areas for differences in cortical thickness and
      MR contrast measures (magnetization transfer ratio (MTR) and signal intensity in
      phase sensitive inversion recovery (PSIR) images) that are sensitive to
      myelination. Consistent area-related differences in cortical thickness and
      MTR/PSIR measurements were found across subjects. However these measures did not
      have sufficient sensitivity to allow definition of areal boundaries.

PMID- 23558100
TI  - Genetic influences on prefrontal activation during a verbal fluency task in
      adults: a twin study based on multichannel near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) studies have reported that prefrontal
      hemodynamic dysfunction during executive function tasks may be a promising
      biomarker of psychiatric disorders, because its portability and noninvasiveness
      allow easy measurements in clinical settings. Here, we investigated the degree to
      which prefrontal NIRS signals are genetically determined. Using a 52-channel NIRS
      system, we monitored the oxy-hemoglobin (oxy-Hb) signal changes in 38 adult pairs
      of right-handed monozygotic (MZ) twins and 13 pairs of same-sex right-handed
      dizygotic (DZ) twins during a letter version of the verbal fluency task.
      Heritability was estimated based on a classical twin paradigm using structured
      equation modeling. Significant genetic influences were estimated in the right
      dorsolateral prefrontal cortex and left frontal pole. The degrees of heritability
      were 66% and 75% in the variances, respectively. This implies that the prefrontal
      hemodynamic dysfunction observed during an executive function task measured by
      NIRS may be an efficient endophenotype for large-scale imaging genetic studies in
      psychiatric disorders. 

PMID- 23558102
TI  - Distinct neural correlates of time-on-task and transient errors during a
      visuomotor tracking task after sleep restriction.
AB  - Sleep loss leads to both time-on-task slowing of responsiveness and increased
      frequency of transient response errors. The consequences of such errors during
      real-world visuomotor tasks, such as driving, are serious and life threatening.
      To investigate the neuronal underpinning of time-on-task and transient errors
      during a visuomotor tracking task following sleep restriction, we performed fMRI
      on 20 healthy individuals when well-rested and when sleep-restricted while they
      performed a 2-D pursuit-tracking task. Sleep restriction to 4-h time-in-bed was
      associated with significant time-on-task decline in tracking performance and an
      increased number of transient tracking errors. Sleep restriction was associated
      with time-on-task decreases in BOLD activity in task-related areas, including the
      lateral occipital cortex, intraparietal cortex, and primary motor cortex. In
      contrast, thalamic, anterior cingulate, and medial frontal cortex areas showed
      overall increases irrespective of time-on-task after sleep-restriction.
      Furthermore, transient errors after sleep-restriction were associated with
      distinct transient BOLD activations in areas not involved in tracking task per
      se, in the right superior parietal cortex, bilateral temporal cortex, and
      thalamus. These results highlight the distinct cerebral underpinnings of
      sustained and transient modulations in alertness during increased homeostatic
      drive to sleep. Ability to detect neuronal changes associated with both sustained
      and transient changes in performance in a single task allowed us to disentangle
      neuronal mechanisms underlying two important aspects of sustained task
      performance following sleep loss.

PMID- 23558103
TI  - The importance of integration and top-down salience when listening to complex
      multi-part musical stimuli.
AB  - In listening to multi-part music, auditory streams can be attended to either
      selectively or globally. More specifically, musicians rely on prioritized
      integrative attention which incorporates both stream segregation and integration
      to assess the relationship between concurrent parts. In this fMRI study, we used
      a piano duet to investigate which factors of a leader-follower relationship
      between parts grab the listener's attention and influence the perception of multi
      part music. The factors considered included the structural relationship between
      melody and accompaniment as well as the temporal relationship (asynchronies)
      between parts. The structural relationship was manipulated by cueing subjects to
      the part of the duet that had to be prioritized. The temporal relationship was
      investigated by synthetically shifting the onset times of melody and
      accompaniment to either a consistent melody or accompaniment lead. The relative
      importance of these relationship factors for segregation and integration as
      attentional mechanisms was of interest. Participants were required to listen to
      the cued part and then globally assess if the prioritized stream was leading or
      following compared to the second stream. Results show that the melody is judged
      as more leading when it is globally temporally ahead whereas the accompaniment is
      not judged as leading when it is ahead. This bias may be a result of the
      interaction of salience of both leader-follower relationship factors.
      Interestingly, the corresponding interaction effect in the fMRI-data yields an
      inverse bias for melody in a fronto-parietal attention network. Corresponding
      parameter estimates within the dlPFC and right IPS show higher neural activity
      for attending to melody when listening to a performance without a temporal
      leader, pointing to an interaction of salience of both factors in listening to
      music. Both frontal and parietal activation implicate segregation and integration
      mechanisms and a top-down influence of salience on attention and the perception
      of leader-follower relations in music.

PMID- 23558104
TI  - Interaction between the electrical stimulation of a face-selective area and the
      perception of face stimuli.
AB  - We electrically stimulated the face-selective area in epileptic patients while
      they were performing a face-categorization task. Face categorization was
      interfered by electrical stimulation but was restored by increasing the visual
      signal. More importantly, face-categorization interference by electrical
      stimulation was confined to face-selective electrodes, and the amount of
      interference was positively correlated with the sensitivity of the face-selective
      electrodes. These results strongly support the hypothesis that the face-selective
      area has a direct causal link to face perception.

PMID- 23558106
TI  - Searchlight analysis: promise, pitfalls, and potential.
AB  - Multivariate pattern analysis (MVPA) is an increasingly popular approach for
      characterizing the information present in neural activity as measured by fMRI.
      For neuroimaging researchers, the searchlight technique serves as the most
      intuitively appealing means of implementing MVPA with fMRI data. However,
      searchlight approaches carry with them a number of special concerns and
      limitations that can lead to serious interpretation errors in practice, such as
      misidentifying a cluster as informative, or failing to detect truly informative
      voxels. Here we describe how such distorted results can occur, using both
      schematic illustrations and examples from actual fMRI datasets. We recommend that
      confirmatory and sensitivity tests, such as the ones prescribed here, should be
      considered a necessary stage of searchlight analysis interpretation, and that
      their adoption will allow the full potential of searchlight analysis to be
      realized.

PMID- 23558105
TI  - Early visual learning induces long-lasting connectivity changes during rest in
      the human brain.
AB  - Spontaneous fluctuations in resting state activity can change in response to
      experience-dependent plasticity and learning. Visual learning is fast and can be
      elicited in an MRI scanner. Here, we showed that a random dot motion coherence
      task can be learned within one training session. While the task activated
      primarily visual and parietal brain areas, learning related changes in neural
      activity were observed in the hippocampus. Crucially, even this rapid learning
      affected resting state dynamics both immediately after the learning and 24h
      later. Specifically, the hippocampus changed its coupling with the striatum, in a
      way that was best explained as a consolidation of early learning related changes.
      Our findings suggest that long-lasting changes in neuronal coupling are
      accompanied by changes in resting state activity.

PMID- 23558107
TI  - Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia:
      Impact of antioxidant vitamin supplementation.
AB  - AIM: To examine the role of placental protein tyrosine nitration and p38-Mitogen
      Activated Protein Kinase alpha (p38-MAPKalpha), Extra Cellular-Signal Regulated
      Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of
      type 1 diabetic pre-eclampsia, and the putative modulation of these indices by
      maternal vitamin C and E supplementation. METHODS: Placental samples were
      obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled
      trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic
      pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational
      hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT
      (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was
      assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic
      activities of placental p38-MAPKalpha, ERK and JNK were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Nitrotyrosine immunostaining was present in
      placebo-treated NT, GH and PE placentae, with no significant difference observed
      between the groups. There was a non-significant trend towards decreased p38
      MAPKalpha activity in PE vs NT control placentae. ERK and JNK were similar among
      the three outcome placebo groups and vitamin supplementation did not
      significantly alter their activity. CONCLUSION: Nitrotyrosine immunopositivity in
      normotensive diabetic placentae indicates some degree of tyrosine nitration in
      uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and
      peroxynitrite production. Our results suggest that p38-MAPKalpha, ERK and JNK are
      not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and
      are not modulated by vitamin-supplementation.

PMID- 23558109
TI  - Development, characterization and application of a new fibroblastic-like cell
      line from kidney of a freshwater air breathing fish Channa striatus (Bloch,
      1793).
AB  - A new cell line, Channa striatus kidney (CSK), derived from the kidney tissue of
      murrel, was established and characterized. The CSK cell line was maintained in
      Leibovitz's L-15 supplemented with 10% fetal bovine serum and has been
      subcultured more than 140 times. This cell line was able to grow in a range of
      temperatures from 22 to 32 degrees C with optimal growth at 28 degrees C. The
      plating efficiency was very high (67.54%) and doubling time was approximately
      29h. The kidney cell line was cryopreserved at different passage levels and
      revived successfully with 90-92% survival. Polymerase chain reaction
      amplification of mitochondrial 16S rRNA using primer specific to C. striatus
      confirmed the origin of this cell line from murrel. The cell line was further
      characterized by chromosome number, transfection and mycoplasma detection. A
      marine fish nodavirus was tested to determine the susceptibility of this new cell
      line. The CSK cell line was found to be susceptible to nodavirus and the
      infection was confirmed by cytopathic effect (CPE), reverse transcriptase
      polymerase chain reaction (RT-PCR), immunodot blot, enzyme linked immunosorbent
      assay (ELISA), virus replication efficiency and real time RT-PCR. The present
      study highlights the development and characterization of a new kidney cell line
      from an air breathing fish that could be used as an in vitro tools for
      propagation of fish viruses and gene expression studies.

PMID- 23558108
TI  - Arterial insulin resistance in Yucatan micropigs with diet-induced obesity and
      metabolic syndrome.
AB  - AIM: Metabolic syndrome affects a large proportion of the population and
      increases cardiovascular disease risk. Because metabolic syndrome often co-exists
      clinically with atherosclerosis, it is difficult to distinguish the respective
      contributions of the components to vascular abnormalities. Accordingly, we
      utilized a porcine dietary model of metabolic syndrome without atherosclerosis to
      investigate early abnormalities of vascular function and signaling. METHODS:
      Thirty-two Yucatan micropigs were fed either a high-fat, high-simple-sugar, high
      calorie (HFHS) or standard chow diet (STD) for 6 months. Neither diet contained
      added cholesterol. Blood pressure and flow-mediated vasodilatation were assessed
      at baseline and 6 months. Aortas were harvested at 6 months to assess histology,
      insulin signaling, and endothelial nitric oxide (eNOS) phosphorylation. RESULTS:
      HFHS pigs developed characteristics of metabolic syndrome including obesity,
      dyslipidemia, and insulin resistance, but without histologic evidence of
      atherosclerosis. Although arterial intima-media thickness did not differ between
      groups, vascular dysfunction in HFHS was manifest by increased blood pressure and
      impaired flow-mediated vasodilation of the femoral artery. Compared with STD,
      aortas from HFHS exhibited increased p85alpha expression and Ser307 IRS-1
      phosphorylation, and blunted insulin-stimulated IRS-1-associated
      phosphatidylinositol (PI) 3-kinase activity. In the absence of insulin
      stimulation, aortic Akt Ser473-phosphorylation was greater in HFHS than in STD.
      With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS.
      Insulin-induced Ser1177-phosphorylation of eNOS was decreased in HFHS, compared
      with STD. CONCLUSIONS: Pigs with metabolic syndrome develop early vascular
      dysfunction and aortic insulin signaling abnormalities, and could be a useful
      model for early human vascular abnormalities in this condition.

PMID- 23558110
TI  - Examining alcohol's contribution to the US African-American/White cirrhosis
      mortality differential from 1950 to 2002.
AB  - AIMS: The aim of this study was to estimate the overall impact of alcohol on US
      race- and sex-specific age-adjusted cirrhosis mortality rates and to consider
      beverage-specific effects that represent changes in drinking patterns over time,
      comparing states with large and small African-American/White cirrhosis mortality
      differentials. METHODS: Using series data from 1950 to 2002, the effects of per
      capita alcohol consumption on cirrhosis mortality for African American and White
      men and women were estimated using generalized least squares panel models on
      first-differenced data. Granger causality tests explored geographic patterning of
      racial differences in cirrhosis mortality. RESULTS: Cirrhosis mortality was
      significantly positively related to apparent consumption of alcohol, with an
      overall impact of 8-14%/l of ethanol. This effect was driven by spirits which
      were more strongly associated with mortality for African-American women and for
      African-American men in states with larger mortality differentials. This
      disparity first emerged in New York and spread through the Northeast and into
      Midwestern states. CONCLUSION: Differences in the contribution of alcohol to
      cirrhosis mortality rates suggest variation by race and gender in life-course
      patterns of heavy consumption, illicit liquor and spirits use, as well as birth
      cohort effects.

PMID- 23558111
TI  - Characterization of functional polymorphisms and glucocorticoid-responsive
      elements in the promoter of TDO2, a candidate gene for ethanol-induced
      behavioural disorders.
AB  - AIMS: In response to acute ethanol consumption, tryptophan 2,3-dioxygenase (TDO)
      induces the kynurenine pathway (KP) through a glucocorticoid-mediated mechanism,
      which could lead to a dramatic accumulation of neurotoxic metabolites in
      association with serotonin depletion. As a result, interindividual variability in
      ethanol-induced behavioural disorders, such as black-outs and violent impulsive
      behaviours (BOVIBs) following binge drinking, could be partly explained by
      genetic polymorphisms affecting the KP. The aim of this study was to identify
      polymorphisms on the promoter of the TDO2 gene that could affect expression
      and/or activity of TDO through glucocorticoid induction. METHODS: Polymorphisms
      were screened using a PCR-sequencing strategy applied to 31 alcohol-dependent
      patients and 49 unrelated healthy volunteers, and functionally analysed with
      bioinformatic prediction tools and gene reporter assays in HepG2 and A549 cell
      lines. RESULTS: We identified 12 polymorphisms in the human TDO2 promoter region,
      2 of them corresponding to previously unknown single-nucleotide polymorphisms
      (SNPs) and 3 of them located in putative glucocorticoid-responsive elements
      (GREs). Gene reporter assays using HepG2 and A549 cell lines confirmed the
      presence of several functional GREs in the promoter region of TDO2 and revealed
      that some of the identified polymorphisms affect the promoter activity under
      glucocorticoid receptor over-expression and dexamethasone exposure conditions.
      CONCLUSIONS: Correlational studies in larger samples could help to determine
      whether these polymorphisms are responsible for variations of expression and/or
      activity of TDO, in particular under conditions where release of glucocorticoids
      is increased, such as acute ethanol intake. If confirmed, such results would be
      of major interest in explaining part of the interindividual variability observed
      in behavioural responses to acute ethanol consumption.

PMID- 23558112
TI  - The association of DRD2 -141C and ANKK1 TaqIA polymorphisms with alcohol
      dependence in Korean population classified by the Lesch typology.
AB  - AIMS: Dopamine receptors are associated with reward and dependence towards
      alcohol. The polymorphisms of dopamine D2 receptor (DRD2) genes have been
      reported to be involved in susceptibility to alcoholism. Therefore, we
      investigated the association of three single-nucleotide polymorphisms (SNPs) in
      DRD2 and ankyrin repeat and kinase domain containing one (ANKK1) genes with
      alcohol dependence in Korean subjects, who were classified by the criteria of the
      Lesch typology. METHODS: The DRD2 -141C (Insertion (Ins)/Deletion (Del)), exon8
      (A/G) and the ANKK1 TaqIA (A1/A2) polymorphisms were genotyped in a case-control
      sample consisting of 245 alcohol-dependent (AD) patients and 110 healthy
      controls. AD patients were classified into four subtypes by the Lesch typology.
      The majority of them (77.1%) were Lesch type 1. Differences in genotype and
      allele frequencies were examined between the AD patients and the controls. Also
      those analyses were done between the Lesch type 1 group and the controls.
      RESULTS: There were significant differences in the genotype and allele
      frequencies of -141C Ins/Del and TaqIA A1/A2 between the AD patients and the
      controls. However, there were no significant differences in genotype or allele
      frequencies of exon8 A/G between the AD patients and the controls. The -141C
      Ins/Ins and TaqIA A1+ variants were associated with Lesch type 1 AD patients.
      When analysing haplotypes of three SNPs, the odds ratio of -141C Ins-A-A1 was
      2.286, while the odds ratio of -141C Del-G-A2 was 0.323. CONCLUSION: The present
      study showed a significant difference in DRD2 -141C and ANKK1 TaqIA polymorphisms
      between the AD patients and the controls. Our findings suggest that -141C Ins and
      TaqIA A1 alleles can be a predisposing factor for alcohol dependence in the
      Korean population.

PMID- 23558113
TI  - Transporting Lazarus: physicians, the state, and the creation of the modern
      paramedic and ambulance, 1955-73.
AB  - In 1966, morticians provided 50 percent of ambulance services in the United
      States; today advanced care by trained medical professionals en route to the
      hospital is considered a basic standard of care. The creation of emergency
      medical services (EMS) provides an important case study for how physicians acting
      as "experts" helped to shape the creation of federal policy in the post-World War
      II years. This paper challenges a narrative of the development of EMS that has
      emphasized technology, individual agency, and the role of fortuitous chance as
      the prime movers of EMS development. Instead it argues that a key factor in EMS
      development was the National Academy of Science-National Research Council's
      Committee on Emergency Medical Services. Using the examples of paramedic training
      and ambulance design, this paper argues that members of the committee utilized
      complex mix of local experimentation and professional networking to suggest
      directions for the federal government's efforts to create national standards and
      guidelines for EMS. The NAS-NRC Committee retained a prominent role in EMS
      development until the passage of the Emergency Medical Services Systems Act of
      1973, when federal interest in EMS largely shifted from prehospital transport to
      an emphasis on in hospital care and regional trauma systems planning.

PMID- 23558117
TI  - Individual differences in preschoolers' emotion content memory: the role of
      emotion knowledge.
AB  - This study examined the relation between preschool children's emotion knowledge
      and their ability to recall emotionally salient information. In total, 42
      participants (ages 35-65months) viewed a brief video in which a child played with
      different toys and expressed one of four basic emotions (happy, sad, angry, or
      afraid) or a neutral expression in each of 10 vignettes. Children were tested on
      memory accuracy from the vignettes, and their emotion knowledge was also
      measured. Results indicated that preschoolers' emotion knowledge was
      significantly related to memory accuracy for emotion information above and beyond
      the effect of age or receptive language skills. Tests of a mediation model
      revealed that emotion knowledge fully mediated the effect of age (or general
      developmental level) on memory accuracy.

PMID- 23558118
TI  - [The use of EUS in the diagnosis and treatment in bilio-pancreatic diseases].

PMID- 23558119
TI  - [Recent advances in EUS-guided biliary drainage].

PMID- 23558120
TI  - [Interventional EUS for pancreatic cystic neoplasms].

PMID- 23558121
TI  - [Interventional EUS for pancreatic pseudocyst and walled-off necrosis].

PMID- 23558122
TI  - [Endoscopic ultrasound-guided rendezvous technique for failed selective biliary
      cannulation].

PMID- 23558124
TI  - [Clinical features and CT findings in the differential diagnosis of IgG4-related
      sclerosing cholangitis and cholangiocarcinoma].
AB  - To clarify the clinical features and CT findings of IgG4-related sclerosing
      cholangitis (IgG4-SC), we reviewed 16 cases of IgG4-SC and 10 cases of
      cholangiocarcinoma concerning patient background, treatment, outcomes and CT
      findings. The median age of IgG4-SC cases was 70 (range 54-79) years, and only 1
      was a woman. Serum IgG4 level of all IgG4-SC patients were elevated and in 13
      patients steroid therapy proved effective. The CT findings were analyzed with
      regard to the biliary strictures (symmetry, outer margin, inner margin), wall
      enhancement pattern and pancreas size. The CT findings of symmetric wall
      thickness and total scores were significantly higher in IgG4-SC than in
      cholangiocarcinoma. Although the small number of patients in this study is a
      limitation, the CT findings may help distinguish IgG4-SC from cholangiocarcinoma.

PMID- 23558126
TI  - [A case of exfoliative esophagitis caused by endoscopic submucosal dissection
      during imatinib treatment for gastrointestinal stromal tumor].
AB  - A woman in her seventies with multiple early stage (0-IIa) gastric cancers was
      undergoing imatinib therapy for gastrointestinal stromal tumor. Subsequently, she
      underwent 2-stage endoscopic submucosal dissection (ESD) for these cancers. Both
      procedures were successful, but she developed exfoliative esophagitis as a
      complication after the first ESD. To prevent this complication after the second
      ESD, we used a longer imatinib withdrawal period before the procedure and used
      general anesthesia during ESD. Although the patient developed exfoliative
      esophagitis after the second ESD, but its severity was less than that after the
      first procedure. Only a few studies have reported endoscopic therapy-induced
      exfoliative esophagitis. We suggest that this complication may be related to
      imatinib-induced mucosal damage.

PMID- 23558125
TI  - [A case of ascending colon neuroendocrine carcinoma drained through a fistula of
      the descending part of the duodenum].
AB  - A 70-year-old woman was admitted for investigation of an abdominal tumor.
      Abdominal CT revealed an ascending colonic mass measuring 10 * 10 cm, with
      evidence of liver and lung metastasis. Colonoscopy revealed a cancerous lesion
      with a central ulcer in the ascending colon. Upper gastrointestinal endoscopy
      revealed an ulcerative lesion in the descending part of the duodenum.
      Histologically, the tumor showed features of neuroendocrine carcinoma. The
      patient died of the primary cancer two and a half months after admission. Autopsy
      revealed a fistula connecting the ascending colonic mass with the ulcerative
      lesion in the duodenum.

PMID- 23558127
TI  - [A case of tacrolimus plus intensive LCAP therapy combination for refractory
      ulcerative colitis].
AB  - A 30-year-old woman was referred to our hospital with recurrent refractory
      ulcerative colitis. She also suffered from avascular necrosis of the left femoral
      head caused by steroid use. We had expected that tacrolimus would contribute to
      remission, but effects remained insufficient even after 16 days of treatment.
      Intensive leukocytapheresis (LCAP) therapy was added to tacrolimus therapy, and
      this combination achieved remission. Tacrolimus plus intensive LCAP combination
      therapy appears useful in treating refractory ulcerative colitis.

PMID- 23558128
TI  - [An autopsy case of ulcerative colitis with disseminated aspergillosis,
      complicated by brain hemorrhage].
AB  - An 80-year-old Japanese woman suffered multiple brain infarctions of unknown
      etiology during maintenance therapy of prednisolone and azathioprine for
      ulcerative colitis. Although a small cavity in the left lung spontaneously
      regressed, the patient suddenly died of massive brain hemorrhage due to
      disseminated aspergillosis, which was not identified until autopsy.

PMID- 23558129
TI  - [A case of osteonecrosis of the jaw during treatment by bevacizumab for sigmoid
      colon cancer].
AB  - A 67-year-old man was diagnosed to have sigmoid colon cancer with peritonitis
      carcinomatosa. The cancer was surgically resected, and he thereafter underwent
      chemotherapy with mFOLFOX6+bevacizumab. He complained of gingival swelling
      throughout treatment and osteonecrosis of the jaw was noted. The bevacizumab
      therapy was therefore discontinued and the necrotic tissue removed. No recurrent
      necrosis has occurred. The addition of bevacizumab to the FOLFOX or FOLFIRI
      chemotherapy regimens has been shown to improve the survival rate and response
      rate in colorectal cancer. Osteonecrosis of the jaw is a rare toxicity of
      bevacizumab. Bevacizumab might compromise the microvessel integrity in the jaw,
      which thus may lead to bone necrosis. Osteonecrosis of the jaw in this case
      recovered after the discontinuation of bevacizumab and the removal of the
      necrotic tissue. The pathogenesis and treatment of osteonecrosis have not been
      elucidated.

PMID- 23558130
TI  - [A case of pancreatic neuroendocrine tumor with excessively-advanced liver
      metastasis treated with S-1/GEM combination chemotherapy plus the long-acting
      somatostatin analogue octreotide].
AB  - A 41-year-old woman who had a pancreatic tail tumor and multiple liver tumors was
      referred to our hospital. The results of abdominal US, CT and MRI, and
      histopathological and immunohistochemical findings of the liver tumor biopsy
      revealed a pancreatic neuroendocrine tumor with excessively-advanced liver
      metastasis. We treated her with S-1/gemcitabine combination chemotherapy plus
      long-acting somatostatin analogue octreotide, which produced tumor stabilization
      and good quality of life for 7 months, and survival time of 15 months. Although
      the tumor was diagnosed as a poorly differentiated endocrine carcinoma, this
      therapy was suggested to be effective in this case.

PMID- 23558131
TI  - [A case of solitary liver tuberculosis diagnosed by TB-PCR and managed
      conservatively].
AB  - A 42-year-old woman was admitted to our hospital with weight loss and right upper
      quadrant abdominal pain. Though an 8cm mass in liver segment 5/8 was detected by
      abdominal imaging, we could not confirm the diagnosis because findings on
      physical examination, blood chemistry, and radiologic examination were
      nonspecific. No cancer or immunocompromising diseases were found. We performed a
      liver biopsy because we were suspicious of a cold abscess caused by tuberculosis.
      Purulent material acquired from the biopsy revealed positive TB-PCR results,
      which confirmed the diagnosis of solitary liver tuberculosis. She received anti
      tuberculosis medications leading to hepatic tumor resolution. There are very few
      reports of solitary liver tuberculosis diagnosed without surgery, thus we report
      this case of a solitary tubercle diagnosed by TB-PCR.

PMID- 23558133
TI  - Suppressor of cytokine signalling protein SOCS1 and UBP43 regulate the expression
      of type I interferon-stimulated genes in human microvascular endothelial cells
      infected with Rickettsia conorii.
AB  - Rickettsia conorii, the causative agent of Mediterranean spotted fever,
      preferentially infects human microvascular endothelium and activates pro
      inflammatory innate immune responses as evidenced by enhanced expression and
      secretion of cytokines and chemokines. Our recent studies reveal that human
      microvascular endothelial cells (HMECs) infected with R. conorii also launch
      'antiviral' host defence mechanisms typically governed by type I interferons. To
      summarize, infected HMECs secrete IFN-beta to activate STAT1 in an
      autocrine/paracrine manner and display increased expression of IFN-stimulated
      genes, for example ISG15, which in turn activate innate responses to interfere
      with intracellular replication of rickettsiae. We now present evidence that UBP43
      and SOCS1, known negative regulators of JAK/STAT signalling, are also induced in
      R. conorii-infected HMECs, of which UBP43 but not SOCS1 functions to negatively
      regulate STAT1 activation. Interestingly, UBP43 induction is almost completely
      abolished in the presence of IFN-beta-neutralizing antibody, implicating an
      important role for UBP43 as a feedback inhibitor for IFN-beta-mediated STAT1
      activation. In contrast, SOCS1 expression is only partially affected by IFN-beta
      neutralization, implicating potential involvement of as-yet-unidentified IFN
      independent mechanism(s) in SOCS1 induction during R. conorii infection. A number
      of IFN-stimulated genes, including ISG15, OAS1, MX1, IRF1, IRF9 and TAP1 are also
      induced in an IFN-beta-dependent manner, whereas GBP1 remains unaffected by IFN
      beta neutralization. Increased STAT1 phosphorylation in HMECs subjected to UBP43
      knockdown led to transcriptional activation of OAS1, MX1 and GBP1, confirming the
      negative regulatory role of UBP43. Although IRF1, IRF9 and TAP1 were induced by
      IFN-beta, siRNA-mediated silencing of UBP43 or SOCS1 did not significantly affect
      their transcriptional activation. Expression of ISG15 was, however, increased in
      HMECs transfected with siRNA for UBP43 and SOCS1. Thus, unique regulatory
      patterns of induced expression of UBP43, SOCS1 and IFN-stimulated genes represent
      pathogen-specific responses underlying IFN-beta-mediated host endothelial
      signalling during the pathogenesis of spotted fever group rickettsiosis.

PMID- 23558134
TI  - Clusters of genetically similar isolates of Pseudomonas aeruginosa from multiple
      hospitals in the UK.
AB  - Variable number tandem repeat (VNTR) analysis at nine loci of isolates of
      Pseudomonas aeruginosa submitted to the national reference laboratory from UK
      hospitals, from over 2000 patients, between June 2010 and June 2012 revealed four
      widely found types that collectively were received from approximately a fifth of
      patients, including from those with cystic fibrosis. These types were also
      prevalent among related submissions from the clinical environment and were
      received from up to 54 (out of 143) hospitals. Multi-locus sequence typing and
      blaOXA-50-like sequencing confirmed the clonal relationship within each cluster,
      and representatives from multiple centres clustered within about 70 % by pulsed
      field gel electrophoresis. Illumina sequencing of 12 isolates of cluster A of
      VNTR profile 8, 3, 4, 5, 2, 3, 5, 2, x (where the repeat number at the last, most
      discriminatory locus is variable) revealed a large number of variably present
      targets in the accessory genome and seven of these were sought by PCR among a
      larger set of isolates. Representatives from patients within a single centre
      mostly had distinct accessory gene profiles, suggesting that these patients
      acquired the strain independently, while those with clear epidemiological links
      shared the same profile. Profiles also varied between representatives from
      different centres. Epidemiological investigations of widely found types such as
      these require the use of finer-typing methods, which increasingly will be
      informed by next generation sequencing.

PMID- 23558135
TI  - Biofilm formation by Staphylococcus capitis strains isolated from contaminated
      platelet concentrates.
AB  - Bacterial contamination of platelet concentrates (PCs) poses the greatest
      infectious risk in modern transfusion medicine despite the implementation of
      measures such as improved skin disinfection and first aliquot diversion. The
      majority of PC contaminants are commensal skin flora introduced by venipuncture
      at the time of blood collection. The predominant organisms are Gram-positive
      coagulase-negative staphylococci such as Staphylococcus capitis. This bacterium
      has been implicated in numerous instances of infection and sepsis, likely for its
      ability to form surface-associated communities of micro-organisms encased in
      extracellular materials, known as biofilms. In the present study, five strains of
      S. capitis isolated from contaminated PCs were assessed for their ability to
      produce extracellular polysaccharide (slime), a canonical indicator of biofilm
      formation ability, on Congo red agar plates. Biofilm formation was evaluated in
      both glucose-enriched trypticase soy broth (TSBg) and in PCs by using a crystal
      violet staining assay. The chemical nature of the biofilms was evaluated by
      disruption assays using sodium metaperiodate and proteinase K. In addition,
      biofilm architecture was observed by scanning electron microscopy. The presence
      of the biofilm-associated icaR and icaADBC genes was also examined by PCR. While
      only two out of the five S. capitis strains formed biofilms in TSBg, all strains
      formed biofilms in PCs. The ability of strains to produce extracellular
      polysaccharide and their possession of wild-type ica genes were not exclusive
      predictors of biofilm formation in TSBg or PCs; different profiles of biofilm
      markers were observed among isolates. This is likely due to the proteinaceous
      composition of the S. capitis biofilm matrix. Interestingly, an ica-negative, non
      slime-producing isolate was capable of biofilm formation in PCs. Together, these
      data indicate that the platelet storage environment stimulates biofilm formation
      in S. capitis in the absence of extracellular polysaccharide production and that
      multiple bacterial factors and regulatory elements are likely involved in biofilm
      formation in this milieu.

PMID- 23558136
TI  - The involvement of Helicobacter pylori thioredoxin-1 in gastric carcinogenesis.
AB  - Helicobacter pylori infection is related to the development of gastric diseases.
      Various virulence factors are responsible for the pathogenic mechanisms of H.
      pylori infection. Our previous studies using two-dimensional gel electrophoresis
      showed that H. pylori thioredoxin-1 (Trx1) is overexpressed in gastric
      carcinomas. Here, we examined whether H. pylori Trx1 is a novel virulence factor
      associated with gastric tumorigenesis. We found that Trx1 expression in H. pylori
      isolated from gastric cancer tissues was significantly higher than that from
      tissues exhibiting gastritis. In the gastric epithelial cell line GES-1,
      infection of H. pylori with high Trx1 expression significantly induced cell
      apoptosis, decreased the expression of cyclin D1 and upregulated p21. However, in
      the gastric cancer cell line BGC823, high Trx1 expression in H. pylori
      significantly increased cell proliferation, and upregulated cyclin D1. The
      effects on cell lines were confirmed using the H. pylori Trx1-knockout mutant
      strain. Our observations indicate that high Trx1 expression in H. pylori is
      associated with gastric carcinogenesis. In H. pylori, Trx1 likely participates in
      the pathogenesis of gastric cancer and H. pylori expressing high levels of Trx1
      would be expected to be highly pathogenic in gastric diseases in China. 

PMID- 23558137
TI  - Two cases of fulminant colitis due to binary toxin-positive Clostridium difficile
      that are not PCR ribotype 027 or type 078.
AB  - Two cases of fulminant colitis due to Clostridium difficile occurred within ten
      weeks of each other on the same ward of a hospital in Japan. The patients died 2
      and 4 days after the onset of colitis. C. difficile isolates obtained from both
      patients were toxin A-positive, toxin B-positive and binary toxin-positive. These
      isolates yielded identical results by both PCR ribotyping and slpA sequence
      typing. However, the banding patterns and slpA sequences of the isolates differed
      from those of PCR ribotype 027, as well as those of PCR ribotype 078. The tcdC
      sequences of the isolate differed from those of C. difficile 027, but a single
      base-pair deletion at position 117 and an 18 bp deletion, both of which were
      identical to the sequence of the reference strain of 027, were found. This type
      may be a new hypervirulent strain, but further studies of the epidemiology and
      pathogenicity of the strain are needed. 

PMID- 23558139
TI  - Selective advantages of two major clones of carbapenem-resistant Pseudomonas
      aeruginosa isolates (CC235 and CC641) from Korea: antimicrobial resistance,
      virulence and biofilm-forming activity.
AB  - The characteristics of carbapenem-resistant P. aeruginosa (CRPA) isolates from
      Korea were investigated. Two major clones, clonal complex (CC) 235 and CC641,
      were identified. CC235, an important international clone, might have been
      imported recently in Korea as this clone displayed a homogeneous genotype, oprD
      mutation and antimicrobial resistance profile. While 13 ST235 isolates harboured
      the blaIMP-6 gene, which conferred high-level meropenem resistance, CC641
      isolates showed high biofilm-forming activity. CC235 and CC641 isolates showed
      distinct distribution of ferripyoverdine receptor type and virulence markers.
      While all CC235 isolates were of the fpvAIIb type and exoS(-)/exoU(+), CC641
      isolates were exoS(+)/exoU(-), and all but one showed the fpvAIII type. CC235 and
      CC641 isolates were also characterized by different extracellular protease
      activity: staphylolysin and elastase activities in CC235 and CC641, respectively.
      Two major CRPA clones in Korea seem to be predominant, reflecting their selective
      advantage by virtue of antimicrobial resistance, virulence and biofilm-forming
      activity.

PMID- 23558138
TI  - Cellular uptake of Clostridium difficile TcdA and truncated TcdA lacking the
      receptor binding domain.
AB  - The combined repetitive oligopeptides (CROPs) of Clostridium difficile toxins A
      (TcdA) and B (TcdB) induce clathrin-mediated endocytosis of the toxins.
      Inconsistently, CROP-truncated TcdA(1-1874) is also capable of entering host
      cells and displaying full cytotoxic properties although with less potency. Pre
      incubation of cells with isolated CROPs, however, reconstitutes the reduced
      uptake of TcdA(1-1874) to the level of the full-length toxin. We believe that
      TcdA exhibits an additional binding motif beyond the C-terminally located CROP
      domain, which might interact with cellular receptor structures that are
      associated with alternative internalization pathways. This study therefore
      evaluated endocytosis routes of CROP-dependent cellular uptake for TcdA and CROP
      independent cellular uptake for TcdA(1-1874). Clathrin knockdown or inhibition
      with chlorpromazine affected subsequent internalization of TcdA and TcdA(1-1874),
      although only to some extent, arguing for alternative, clathrin-independent
      endocytosis routes. Inhibition of dynamin, a GTPase essentially involved in
      clathrin-mediated endocytosis as well as in various clathrin-independent uptake
      mechanisms, affected uptake of TcdA to the same extent as clathrin inhibition. In
      contrast, uptake of TcdA(1-1874) was almost completely eliminated in dynamin
      inhibited cells. Thus, clathrin-independent uptake of TcdA(1-1874) presumably
      depends on dynamin. These findings demonstrate that the toxins are endocytosed
      via complex pathways involving clathrin and dynamin, putatively enabling them to
      adapt to mechanisms of various cell types. With regard to the emergence of C.
      difficile strains producing C-terminally truncated toxins, this study emphasizes
      the relevance of elucidating toxin uptake as a prerequisite for the development
      of toxin intervention strategies. 

PMID- 23558140
TI  - Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and
      current perspectives.
AB  - Colorectal cancer (CRC) is the third most common form of cancer. Diverse
      therapies such as chemotherapy, immunotherapy and radiation have shown beneficial
      effects, but are limited because of their safety and toxicity. Probiotic
      formulations have shown great promise in CRC as preventive and early stage
      therapeutics. This review highlights the importance of a balanced intestinal
      microbiota and summarizes the recent developments in probiotics for treating CRC.
      Specifically, this report describes evidence of the role of probiotics in
      modulating the microbiota, in improving the physico-chemical conditions of the
      gut and in reducing oxidative stress. It also discusses the mechanisms of
      probiotics in inhibiting tumour progression, in producing anticancer compounds
      and in modulating the host immune response. Even though some of these effects
      were observed in several clinical trials, when probiotic formulations were used
      as a supplement to CRC therapies, the application of probiotics as
      biotherapeutics against CRC still needs further investigation. 

PMID- 23558141
TI  - Enterobacter cloacae producing an uncommon class A carbapenemase, IMI-1, from
      Singapore.
AB  - In this study, we describe the characterization of an infrequently encountered
      class A carbapenemase, IMI-1, from a clinical Enterobacter cloacae isolate. The
      isolate had high levels of resistance to carbapenems but retained susceptibility
      to expanded-spectrum cephalosporins. The blaIMI-1 gene was chromosomally encoded.
      Detection of the IMI-1 producer highlights the diversity of carbapenemases in a
      local clinical setting.

PMID- 23558143
TI  - Alteration of synaptic activity-regulating genes underlying functional
      improvement by long-term exposure to an enriched environment in the adult brain.
AB  - BACKGROUND: Housing animals in an enriched environment (EE) enhances behavioral
      function. However, the mechanism underlying this EE-mediated functional
      improvement and the resultant changes in gene expression have yet to be
      elucidated. OBJECTIVES: We attempted to investigate the underlying mechanisms
      associated with long-term exposure to an EE by evaluating gene expression
      patterns. METHODS: We housed 6-week-old CD-1 (ICR) mice in standard cages or an
      EE comprising a running wheel, novel objects, and social interaction for 2
      months. Motor and cognitive performances were evaluated using the rotarod test
      and passive avoidance test, and gene expression profile was investigated in the
      cerebral hemispheres using microarray and gene set enrichment analysis (GSEA).
      RESULTS: In behavioral assessment, an EE significantly enhanced rotarod
      performance and short-term working memory. Microarray analysis revealed that
      genes associated with neuronal activity were significantly altered by an EE. GSEA
      showed that genes involved in synaptic transmission and postsynaptic signal
      transduction were globally upregulated, whereas those associated with reuptake by
      presynaptic neurotransmitter transporters were downregulated. In particular, both
      microarray and GSEA demonstrated that EE exposure increased opioid signaling,
      acetylcholine release cycle, and postsynaptic neurotransmitter receptors but
      decreased Na+ / Cl- -dependent neurotransmitter transporters, including dopamine
      transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32
      (PPP1R1B), and P2RY12 were largely altered in a region-specific manner.
      CONCLUSION: An EE enhanced motor and cognitive function through the alteration of
      synaptic activity-regulating genes, improving the efficient use of
      neurotransmitters and synaptic plasticity by the upregulation of genes associated
      with postsynaptic receptor activity and downregulation of presynaptic reuptake by
      neurotransmitter transporters.

PMID- 23558144
TI  - Determination and verification of a 2D pencil-beam kernel for a radiosurgery
      system with cones.
AB  - The quality and correctness of dosimetric data of small fields in stereotactic
      radiosurgery (SRS) depends significantly on the election of the detector employed
      in the measurements. This work provides an independent method of verification of
      these data through the determination of a polyenergetic 2-dimensional pencil-beam
      kernel for a BrainLAB SRS system with cones, employing the
      deconvolution/convolution of a reference experimental off-axis ratio (OAR)
      profile (cone diameter c0 = 35 mm). The kernel in real space k(c(0))(r,z(0)) is
      convolved with the ideal fluence Phi for the cones 7.5 to 35 mm in diameter to
      obtain the OAR profiles, and the total scatter factors, St, which are compared
      with experimental values of the same quantities. The experimental OARs and St
      factors are measured in water with a PTW 60003 diamond detector. Additionally,
      the reference OAR is corrected for beam divergence and spectral fluence
      fluctuations defining a function of boundary correction factors (BF). The BF and
      Phi functions are transformed to the conjugate space with the zeroth-order Hankel
      transform, appropriated to the radial symmetry of the cones. Therefore, the
      kernel in real space k(c(0))(r,z(0)) is the inverse Hankel transform of the ratio
      of the Hankel transforms of BF and Phi. Finally, an uncertainty analysis
      according to the Guide to the Expression of Uncertainty in Measurement is carried
      out for 3 different values of k(c(0))(r,z(0)). Calculated and measured OARs agree
      within the dose/distance-to-agreement criteria of 2%/0.12 mm; while, St factors
      agree within 2%. This procedure supplies an independent method to validate the
      dosimetric data necessary to feed treatment planning systems for SRS with cones.

PMID- 23558145
TI  - Quantitative assessment of the accuracy of dose calculation using pencil beam and
      Monte Carlo algorithms and requirements for clinical quality assurance.
AB  - To compare the doses calculated using the BrainLAB pencil beam (PB) and Monte
      Carlo (MC) algorithms for tumors located in various sites including the lung and
      evaluate quality assurance procedures required for the verification of the
      accuracy of dose calculation. The dose-calculation accuracy of PB and MC was also
      assessed quantitatively with measurement using ionization chamber and Gafchromic
      films placed in solid water and heterogeneous phantoms. The dose was calculated
      using PB convolution and MC algorithms in the iPlan treatment planning system
      from BrainLAB. The dose calculation was performed on the patient's computed
      tomography images with lesions in various treatment sites including 5 lungs, 5
      prostates, 4 brains, 2 head and necks, and 2 paraspinal tissues. A combination of
      conventional, conformal, and intensity-modulated radiation therapy plans was used
      in dose calculation. The leaf sequence from intensity-modulated radiation therapy
      plans or beam shapes from conformal plans and monitor units and other planning
      parameters calculated by the PB were identical for calculating dose with MC.
      Heterogeneity correction was considered in both PB and MC dose calculations. Dose
      volume parameters such as V95 (volume covered by 95% of prescription dose), dose
      distributions, and gamma analysis were used to evaluate the calculated dose by PB
      and MC. The measured doses by ionization chamber and EBT GAFCHROMIC film in solid
      water and heterogeneous phantoms were used to quantitatively asses the accuracy
      of dose calculated by PB and MC. The dose-volume histograms and dose
      distributions calculated by PB and MC in the brain, prostate, paraspinal, and
      head and neck were in good agreement with one another (within 5%) and provided
      acceptable planning target volume coverage. However, dose distributions of the
      patients with lung cancer had large discrepancies. For a plan optimized with PB,
      the dose coverage was shown as clinically acceptable, whereas in reality, the MC
      showed a systematic lack of dose coverage. The dose calculated by PB for lung
      tumors was overestimated by up to 40%. An interesting feature that was observed
      is that despite large discrepancies in dose-volume histogram coverage of the
      planning target volume between PB and MC, the point doses at the isocenter
      (center of the lesions) calculated by both algorithms were within 7% even for
      lung cases. The dose distributions measured with EBT GAFCHROMIC films in
      heterogeneous phantoms showed large discrepancies of nearly 15% lower than PB at
      interfaces between heterogeneous media, where these lower doses measured by the
      film were in agreement with those by MC. The doses (V95) calculated by MC and PB
      agreed within 5% for treatment sites with small tissue heterogeneities such as
      the prostate, brain, head and neck, and paraspinal tumors. Considerable
      discrepancies, up to 40%, were observed in the dose-volume coverage between MC
      and PB in lung tumors, which may affect clinical outcomes. The discrepancies
      between MC and PB increased for 15MV compared with 6MV indicating the importance
      of implementation of accurate clinical treatment planning such as MC. The
      comparison of point doses is not representative of the discrepancies in dose
      coverage and might be misleading in evaluating the accuracy of dose calculation
      between PB and MC. Thus, the clinical quality assurance procedures required to
      verify the accuracy of dose calculation using PB and MC need to consider
      measurements of 2- and 3-dimensional dose distributions rather than a single
      point measurement using heterogeneous phantoms instead of homogenous water
      equivalent phantoms. 

PMID- 23558146
TI  - A quantitative assessment of volumetric and anatomic changes of the parotid gland
      during intensity-modulated radiotherapy for head and neck cancer using serial
      computed tomography.
AB  - To evaluate the change in volume and movement of the parotid gland measured by
      serial contrast-enhanced computed tomography scans in patients with head and neck
      cancer treated with parotid-sparing intensity-modulated radiotherapy (IMRT). A
      prospective study was performed on 13 patients with head and neck cancer
      undergoing dose-painted IMRT to 69.96Gy in 33 fractions. Serial computed
      tomography scans were performed at baseline, weeks 2, 4, and 6 of radiotherapy
      (RT), and at 6 weeks post-RT. The parotid volume was contoured at each scan, and
      the movement of the medial and lateral borders was measured. The patient's body
      weight was recorded at each corresponding week during RT. Regression analyses
      were performed to ascertain the rate of change during treatment as a percent
      change per fraction in parotid volume and distance relative to baseline. The mean
      parotid volume decreased by 37.3% from baseline to week 6 of RT. The overall rate
      of change in parotid volume during RT was-1.30% per fraction (-1.67% and-0.91%
      per fraction in>=31Gy and<31Gy mean planned parotid dose groups, respectively, p
      = 0.0004). The movement of parotid borders was greater in the>=31Gy mean parotid
      dose group compared with the<31Gy group (0.22% per fraction and 0.14% per
      fraction for the lateral border and 0.19% per fraction and 0.06% per fraction for
      the medial border, respectively). The median change in body weight was-7.4%
      (range, 0.75% to-17.5%) during RT. A positive correlation was noted between
      change in body weight and parotid volume during the course of RT (Spearman
      correlation coefficient, r = 0.66, p<0.01). Head and neck IMRT results in a
      volume loss of the parotid gland, which is related to the planned parotid dose,
      and the patient's weight loss during RT. 

PMID- 23558147
TI  - Quantitative characterization of tomotherapy MVCT dosimetry.
AB  - Megavoltage computed tomography (MVCT) is used as image guidance for patient
      setup in almost every tomotherapy treatment. Frequent use of ionizing radiation
      for image guidance has raised concern of imaging dose. The purpose of this work
      is to quantify and characterize tomotherapy MVCT dosimetry. Our dose calculation
      was based on a commissioned dose engine, and the calculation result was compared
      with film measurement. We studied dose profiles, center dose, maximal dose,
      surface dose, and mean dose on homogeneous cylindrical water phantoms of various
      diameters for various scanning parameters, including 3 different jaw openings (of
      nominal value J4, J1, and J0.1) and couch speeds (fine, normal, and coarse). The
      comparison between calculation and film measurement showed good agreement. In
      particular, the thread pattern on the film of the helical delivery matched very
      well with calculation. For the J1 jaw and coarse imaging mode, the maximum
      difference between calculation and measurement was about 6% of the center dose.
      Calculation on various sizes of synthesized phantoms showed that the center dose
      decreases almost linearly as the phantom diameter increases, and that the fine
      mode (couch speed of 4mm/rotation) received twice the dose of the normal mode
      (couch speed of 8mm/rotation) and 3 times that of the coarse mode (couch speed of
      12mm/rotation) as expected. The maximal dose ranged from 100% to ~200% of the
      center dose, with increasing ratios for larger phantoms, smaller jaws, and faster
      couch speed. For all jaw settings and couch speeds, the mean dose and average
      surface dose vary from 95% to 125% of the center dose with increasing ratios for
      larger phantoms. We present a quantitative dosimetric characterization of the
      tomotherapy MVCT in terms of scanning parameters, phantom size, center dose,
      maximal dose, surface dose, and mean dose. The results can provide an overall
      picture of dose distribution and a reference data set that enables estimation of
      CT dose index for the tomotherapy MVCT. 

PMID- 23558149
TI  - How emergency physicians use biomarkers: insights from a qualitative assessment
      of script concordance tests.
AB  - OBJECTIVES: Biomarkers have been developed in emergency medicine to improve
      decision at bedside using Bayesian approach. We intend to determine the cognitive
      process actually utilised by emergency physicians to incorporate biomarkers in
      clinical reasoning. DESIGN: We invited eight emergency physicians to answer eight
      script concordance tests. Interviews were tape-recorded and qualitatively
      analysed using predetermined categories until saturation. RESULTS: Emergency
      physicians mainly mobilised intuition and non-Bayesian reasoning to incorporate
      biomarkers for diagnosis or treatment strategies. CONCLUSIONS: Although
      biomarkers have been developed to be used in a Bayesian approach, emergency
      physicians mainly use other analytical and non-analytical cognitive processes to
      introduce these tools in their clinical reasoning.

PMID- 23558148
TI  - Invasion of E. coli biofilms by antibiotic resistance plasmids.
AB  - In spite of the contribution of plasmids to the spread of antibiotic resistance
      in human pathogens, little is known about the transferability of various drug
      resistance plasmids in bacterial biofilms. The goal of this study was to compare
      the efficiency of transfer of 19 multidrug resistance plasmids into Escherichia
      coli recipient biofilms and determine the effects of biofilm age, biofilm-donor
      exposure time, and donor-to-biofilm attachment on this process. An E. coli
      recipient biofilm was exposed separately to 19 E. coli donors, each with a
      different plasmid, and transconjugants were determined by plate counting. With
      few exceptions, plasmids that transferred well in a liquid environment also
      showed the highest transferability in biofilms. The difference in transfer
      frequency between the most and least transferable plasmid was almost a million
      fold. The 'invasibility' of the biofilm by plasmids, or the proportion of biofilm
      cells that acquired plasmids within a few hours, depended not only on the type of
      plasmid, but also on the time of biofilm exposure to the donor and on the ability
      of the plasmid donor to attach to the biofilm, yet not on biofilm age. The
      efficiency of donor strain attachment to the biofilm was not affected by the
      presence of plasmids. The most invasive plasmid was pHH2-227, which based on
      genome sequence analysis is a hybrid between IncU-like and IncW plasmids. The
      wide range in transferability in an E. coli biofilm among plasmids needs to be
      taken into account in our fight against the spread of drug resistance.

PMID- 23558150
TI  - Web-based general public opinion study of automated versus manual external chest
      compression.
AB  - BACKGROUND: Only a few cardiac-arrest victims receive external chest compression
      (ECC) by a bystander. OBJECTIVE: To test the hypothesis that the general public
      might start ECC more often if they used an automated device rather than a manual
      massage. METHODS: Web-based public opinion survey based on two short videos, one
      showing manual ECC and the other automated ECC (Autopulse, Zoll, France).
      Advantages and disadvantages (perceived efficacy, reproducibility, hazard,
      apprehension and acceptability) of the two techniques were evaluated on a visual
      analogue scale (VAS). A VAS of 1-3 was considered to indicate preference for
      manual ECC, 8-10 for automated ECC and 4-7 for no clear preference. The final
      global score was the difference between advantage and disadvantage scores.
      RESULTS: Overall, 1769 persons answered the questionnaire. The median VAS score
      for each variable was as follows: 7 (25-75 percentiles, 5-9) for efficacy, 8 (3
      10) for reproducibility, 5 (3-8) for hazard, 5 (2-8) for apprehension and 5 (2-8)
      for acceptability. The overall median score indicated that 1034 persons (58%)
      preferred use of the device, 618 (35%) preferred manual ECC and 117 (7%) had no
      preference. There was no significant difference in the preference according to
      gender, education and training in first aid. However, older persons (0) preferred
      the use of device. CONCLUSIONS: The better 'advantages over disadvantages' score
      for the automated ECC device over manual ECC indicated that the general public
      might envisage use of the device. This could contribute to increase the frequency
      of resuscitation attempts by bystanders.

PMID- 23558151
TI  - Weather factors associated with paediatric croup presentations to an Australian
      emergency department.
AB  - We examined if croup presentations to the emergency department (ED) were
      associated with weather changes in a warm temperate climate. We collected data on
      all 729 cases with an ED discharge or admission diagnosis of croup over a 798 day
      time period. We obtained detailed climatic records from the New South Wales
      Meteorological Office for the same time period. Only one daily variable, ground
      temperature at 9:00, was significantly associated with the number of croup
      attendances (linear regression -0.2062; 95% CI -0.272 to -0.138). There was a
      stronger correlation (-0.426; 95% CI -0.684 to -0.072) between the calculated
      mean monthly temperature and the monthly number of croup admissions. Even in this
      milder climate, croup is associated with cooler weather. We are unable to
      conclude that hospital attendances for croup are caused by changes in temperature
      alone, as other factors such as the prevalence of viral illness also follow a
      seasonal, and therefore, temperature-related pattern. 

PMID- 23558152
TI  - Near death by central line.

PMID- 23558153
TI  - An unusual dental complication.

PMID- 23558154
TI  - Strategy sequential difficulty effects vary with working-memory and response
      stimulus-intervals: a study in arithmetic.
AB  - Strategy sequential difficulty effects are the findings that when participants
      execute strategies, performance is worse after a difficult strategy than after an
      easy strategy (Uittenhove & Lemaire, 2012). Strategy sequential difficulty
      effects are hypothesized to result from decreased working-memory resources
      following difficult strategy execution. In the present study we found a
      correlation between individuals' working memory and strategy sequential
      difficulty effects in arithmetic, supporting a working-memory account of these
      effects. Furthermore, we varied response-stimulus intervals, and we found
      decreased strategy sequential difficulty effects with increasing response
      stimulus intervals. Implications of these findings for further understanding of
      strategic variations in human cognition are discussed.

PMID- 23558155
TI  - Effects of practice on variability in an isochronous serial interval production
      task: asymptotical levels of tapping variability after training are similar to
      those of musicians.
AB  - Timing permeates everyday activities such as walking, dancing and music, yet the
      effect of short-term practice in this ubiquitous activity is largely unknown. In
      two training experiments involving sessions spread across several days, we
      examined short-term practice effects on timing variability in a sequential
      interval production task. In Experiment 1, we varied the mode of response (e.g.,
      drumstick and finger tapping) and the level of sensory feedback. In Experiment 2
      we varied the interval in 18 levels ranging from 500 ms to 1624 ms. Both
      experiments showed a substantial decrease in variability within the first hour of
      practice, but little thereafter. This effect was similar across mode of response,
      amount of feedback, and interval duration, and was manifested as a reduction in
      both local variability (between neighboring intervals) and drift (fluctuation
      across multiple intervals). The results suggest mainly effects on motor
      implementation rather than on cognitive timing processes, and have methodological
      implications for timing studies that have not controlled for practice.

PMID- 23558156
TI  - 1-Phenil-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia.
AB  - Inflammation plays a central role in the pathogenesis of several brain disorders
      and neuronal injury, and it develops as a consequence of glial cell activation.
      Activated microglial cells generate potentially damaging nitric oxide, oxygen
      free radicals, prostanoids, and pro-inflammatory cytokines. Naturally occurring
      polyphenols have recently received attention for their potential protective
      effect on neurodegenerative disorders characterized by microglial activation, due
      to their anti-inflammatory and antioxidant properties. In the present study, we
      investigated, using an in vitro model of primary microglia, the ability of 1
      phenyl-6,7-dihydroxy-isochroman (encoded L 137), a natural polyphenolic compound,
      to inhibit microglia activation induced by an inflammatory insult. So, L137
      effects (1-100 MUM) on production of pro-inflammatory mediators in
      lipopolysaccharide (LPS)-activated microglial cells were evaluated. The
      expression of inducible isoforms of nitric oxide synthase (iNOS) and
      cyclooxygenase (COX-2) as well as of the nuclear transcription Factor-kappa B (NF
      kappaB) was also performed in cellular lysates by Immunoblot. L137 significantly
      reduced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6
      secretion, as well as nitric oxide (NO) and prostanoids [Thromboxane (TX)B2,
      prostaglandin (PG)E2] production in activated microglial cells. Western blot
      analyses showed an inhibitory effect of L137 on the iNOS and COX-2 expression,
      mediated by a modulation of redox-sensitive nuclear transcriptional factor (NF)
      kappaB, known to control a wide array of genes involved in inflammation. In
      conclusion, this study demonstrate that L137 is able to inhibit the production of
      pro-inflammatory and neurotoxic mediators by LPS-activated microglial cells thus
      suggesting L137 as a potential lead compound for drug development for
      neurodegenerative disorders where microglia-mediated inflammatory responses play
      an important pathogenic role.

PMID- 23558157
TI  - Virological analysis of once-daily and twice-daily darunavir/ritonavir in the
      ODIN trial of treatment-experienced patients.
AB  - BACKGROUND: The aim of this analysis was to characterize viral resistance in the
      Phase III, randomized ODIN trial, which demonstrated non-inferiority of once
      daily darunavir/ritonavir (DRV/r) 800/100 mg to DRV/r 600/100 mg twice daily,
      each combined with an optimized background regimen in treatment-experienced
      patients with no DRV resistance-associated mutations (RAMs) at screening.
      METHODS: Virological failure (VF) was defined as never achieving or losing
      confirmed virological suppression after week 12, with patients being classed as
      'never suppressed' (never achieved HIV-1 RNA<50 copies/ml) or 'rebounders'
      (achieved two consecutive HIV-1 RNA<50 copies/ml but then >= 50 copies/ml).
      Phenotypes and genotypes of plasma HIV-1 viruses, using population-based
      sequencing and Antivirogram((r)), were determined at screening/baseline and on
      samples from VFs with HIV-1 RNA >= 50 copies/ml. RESULTS: Mean baseline HIV-1 RNA
      was 4.16 log10 copies/ml and 53.9% of patients were protease inhibitor (PI)
      experienced at enrolment. VF rate was similar in both arms. A similar proportion
      of virologically failing patients in both arms developed PI RAMs (11.7% versus
      9.5%, respectively) or nucleoside reverse transcriptase inhibitor RAMs (6.7%
      versus 7.1%). One patient with VF (once-daily arm) developed four primary PI
      mutations, three of which were also DRV RAMs. This patient was also the only VF
      to lose susceptibility to DRV. Loss of susceptibility to other PIs (once daily
      3.4%; twice daily 0%) and nucleoside reverse transcriptase inhibitors (once daily
      13.6%; twice daily 9.8%) in VF patients was infrequent and comparable between
      treatment arms. CONCLUSIONS: These analyses showed once-daily DRV/r 800/100 mg
      was associated with similar rates of VF and emergence of resistance as DRV/r
      600/100 mg twice daily in treatment-experienced patients with no DRV RAMs.

PMID- 23558159
TI  - Species tree phylogeny and character evolution in the genus Centipeda
      (Asteraceae): evidence from DNA sequences from coding and non-coding loci from
      the plastid and nuclear genomes.
AB  - A species tree phylogeny of the Australian/New Zealand genus Centipeda
      (Asteraceae) is estimated based on nucleotide sequence data. We analysed
      sequences of nuclear ribosomal DNA (ETS, ITS) and three plasmid loci (ndhF, psbA
      trnH, and trnL-F) using the multi-species coalescent module in BEAST. A total of
      129 individuals from all 10 recognised species of Centipeda were sampled
      throughout the species distribution ranges, including two subspecies. We conclude
      that the inferred species tree topology largely conform previous assumptions on
      species relationships. Centipeda racemosa (Snuffweed) is the sister to remaining
      species, which is also the only consistently perennial representative in the
      genus. Centipeda pleiocephala (Tall Sneezeweed) and C. nidiformis (Cotton
      Sneezeweed) constitute a species pair, as does C. borealis and C. minima
      (Spreading Sneezeweed), all sharing the symplesiomorphic characters of spherical
      capitulum and convex receptacle with C. racemosa. Another species group
      comprising C. thespidioides (Desert Sneezeweed), C. cunninghamii (Old man weed,
      or Common sneeze-weed), C. crateriformis is well-supported but then include the
      morphologically aberrant C. aotearoana, all sharing the character of having
      capitula that mature more slowly relative the subtending shoot. Centipeda
      elatinoides takes on a weakly supported intermediate position between the two
      mentioned groups, and is difficult to relate to any of the former groups based on
      morphological characters.

PMID- 23558158
TI  - Synergy between seeking safety and twelve-step affiliation on substance use
      outcomes for women.
AB  - OBJECTIVE: The Recovery Management paradigm provides a conceptual framework for
      the examination of joint impact of a focal treatment and post-treatment service
      utilization on substance abuse treatment outcomes. We test this framework by
      examining the interactive effects of a treatment for comorbid PTSD and substance
      use, Seeking Safety, and post-treatment Twelve-Step Affiliation (TSA) on alcohol
      and cocaine use. METHOD: Data from 353 women in a six-site, randomized controlled
      effectiveness trial within the NIDA Clinical Trials Network were analyzed under
      latent class pattern mixture modeling. LCPMM was used to model variation in
      Seeking Safety by TSA interaction effects on alcohol and cocaine use. RESULTS:
      Significant reductions in alcohol use among women in Seeking Safety (compared to
      health education) were observed; women in the Seeking Safety condition who
      followed up with TSA had the greatest reductions over time in alcohol use.
      Reductions in cocaine use over time were also observed but did not differ between
      treatment conditions nor were there interactions with post-treatment TSA.
      CONCLUSIONS: Findings advance understanding of the complexities for treatment and
      continuing recovery processes for women with PTSD and SUDs, and further support
      the chronic disease model of addiction.

PMID- 23558160
TI  - Acute monoarthritis as presenting manifestation of acute Q fever: report of a new
      case and literature review.

PMID- 23558161
TI  - High-resolution transrectal ultrasound: pilot study of a novel technique for
      imaging clinically localized prostate cancer.
AB  - OBJECTIVES: To determine how high-resolution transrectal ultrasound (HiTRUS)
      compares with conventional TRUS (LoTRUS) for the visualization of prostate
      cancer. METHODS AND MATERIALS: Twenty-five men with known prostate cancer
      scheduled for radical prostatectomy were preoperatively imaged with both LoTRUS
      (5MHz) and HiTRUS (21MHz). Dynamic cine loops and still images for each modality
      were saved and subjected to blinded review by a radiologist looking for
      hypoechoic foci >= 5 mm in each sextant of the prostate. Following prostatectomy,
      areas of prostate cancer >= 5 mm on pathologic review were anatomically
      correlated to LoTRUS and HiTRUS findings. The accuracy of LoTRUS and HiTRUS to
      visualize prostate cancer in each sextant of the prostate and to identify high
      grade and locally advanced disease was assessed. The McNemar test was used to
      compare sensitivity and specificity and paired dichotomous outcomes between
      imaging modalities. RESULTS: Among 69 sextants with pathologically identified
      cancerous foci at radical prostatecomy, HiTRUS visualized 45 and missed 24,
      whereas LoTRUS visualized 26 and missed 43. Compared with LoTRUS, HiTRUS
      demonstrated improved sensitivity (65.2% vs. 37.7%) and specificity (71.6% vs.
      65.4%). HiTRUS's agreement with pathologic findings was twice as high as LoTRUS
      (P = 0.006). HiTRUS provided a nonsignificant increase in visualization of high
      grade lesions (84% vs. 60%, P = 0.11). CONCLUSIONS: HiTRUS appears promising for
      prostate cancer imaging. Our initial experience suggests superiority to LoTRUS
      for the visualization of cancerous foci, and supports proceeding with a clinical
      trial in the biopsy setting.

PMID- 23558162
TI  - Effect of longer term modest salt reduction on blood pressure: Cochrane
      systematic review and meta-analysis of randomised trials.
AB  - OBJECTIVE: To determine the effects of longer term modest salt reduction on blood
      pressure, hormones, and lipids. DESIGN: Systematic review and meta-analysis. DATA
      SOURCES: Medline, Embase, Cochrane Hypertension Group Specialised Register,
      Cochrane Central Register of Controlled Trials, and reference list of relevant
      articles. INCLUSION CRITERIA: Randomised trials with a modest reduction in salt
      intake and duration of at least four weeks. DATA EXTRACTION AND ANALYSIS: Data
      were extracted independently by two reviewers. Random effects meta-analyses,
      subgroup analyses, and meta-regression were performed. RESULTS: Thirty four
      trials (3230 participants) were included. Meta-analysis showed that the mean
      change in urinary sodium (reduced salt v usual salt) was -75 mmol/24 h
      (equivalent to a reduction of 4.4 g/day salt), and with this reduction in salt
      intake, the mean change in blood pressure was -4.18 mm Hg (95% confidence
      interval -5.18 to -3.18, I(2)=75%) for systolic blood pressure and -2.06 mm Hg (
      2.67 to -1.45, I(2)=68%) for diastolic blood pressure. Meta-regression showed
      that age, ethnic group, blood pressure status (hypertensive or normotensive), and
      the change in 24 hour urinary sodium were all significantly associated with the
      fall in systolic blood pressure, explaining 68% of the variance between studies.
      A 100 mmol reduction in 24 hour urinary sodium (6 g/day salt) was associated with
      a fall in systolic blood pressure of 5.8 mm Hg (2.5 to 9.2, P=0.001) after
      adjustment for age, ethnic group, and blood pressure status. For diastolic blood
      pressure, age, ethnic group, blood pressure status, and the change in 24 hour
      urinary sodium explained 41% of the variance between studies. Meta-analysis by
      subgroup showed that in people with hypertension the mean effect was -5.39 mm Hg
      (-6.62 to -4.15, I(2)=61%) for systolic blood pressure and -2.82 mm Hg (-3.54 to 
      2.11, I(2)=52%) for diastolic blood pressure. In normotensive people, the figures
      were -2.42 mm Hg (-3.56 to -1.29, I(2)=66%) and -1.00 mm Hg (-1.85 to -0.15,
      I(2)=66%), respectively. Further subgroup analysis showed that the decrease in
      systolic blood pressure was significant in both white and black people and in men
      and women. Meta-analysis of data on hormones and lipids showed that the mean
      change was 0.26 ng/mL/h (0.17 to 0.36, I(2)=70%) for plasma renin activity, 73.20
      pmol/L (44.92 to 101.48, I(2)=62%) for aldosterone, 187 pmol/L (39 to 336,
      I(2)=5%) for noradrenaline (norepinephrine), 37 pmol/L (-1 to 74, I(2)=12%) for
      adrenaline (epinephrine), 0.05 mmol/L (-0.02 to 0.11, I(2)=0%) for total
      cholesterol, 0.05 mmol/L (-0.01 to 0.12, I(2)=0%) for low density lipoprotein
      cholesterol, -0.02 mmol/L (-0.06 to 0.01, I(2)=16%) for high density lipoprotein
      cholesterol, and 0.04 mmol/L (-0.02 to 0.09, I(2)=0%) for triglycerides.
      CONCLUSIONS: A modest reduction in salt intake for four or more weeks causes
      significant and, from a population viewpoint, important falls in blood pressure
      in both hypertensive and normotensive individuals, irrespective of sex and ethnic
      group. Salt reduction is associated with a small physiological increase in plasma
      renin activity, aldosterone, and noradrenaline and no significant change in lipid
      concentrations. These results support a reduction in population salt intake,
      which will lower population blood pressure and thereby reduce cardiovascular
      disease. The observed significant association between the reduction in 24 hour
      urinary sodium and the fall in systolic blood pressure, indicates that larger
      reductions in salt intake will lead to larger falls in systolic blood pressure.
      The current recommendations to reduce salt intake from 9-12 to 5-6 g/day will
      have a major effect on blood pressure, but a further reduction to 3 g/day will
      have a greater effect and should become the long term target for population salt
      intake.

PMID- 23558165
TI  - Role of messenger RNA-ribosome complex in complementary DNA display.
AB  - In vitro display technologies such as ribosome display and messenger RNA
      (mRNA)/complementary DNA (cDNA) display are powerful methods that can generate
      library diversities on the order of 10(10-14). However, in mRNA and cDNA display
      methods, the end use diversity is two orders of magnitude lower than initial
      diversity and is dependent on the downstream processes that act as limiting
      factors. We found that in our previous cDNA display protocol, the purification of
      protein fusions by the use of streptavidin matrices from cell-free translation
      mixtures had poor efficiency (~10-15%) that seriously affected the diversity of
      the purified library. Here, we have investigated and optimized the protocols that
      provided remarkable purification efficiencies. The stalled ribosome in the mRNA
      ribosome complex was found to impede this purification efficiency. Among the
      various conditions tested, destabilization of ribosomes by appropriate
      concentration of metal chelating agents in combination with an optimal
      temperature of 30 degrees C were found to be crucial and effective for nearly
      complete isolation of protein fusions from the cell-free translation system.
      Thus, this protocol provided 8- to 10-fold increased efficiency of purification
      over the previous method and results in retaining the diversity of the library by
      approximately an order of magnitude-important for directed evolution. We also
      discuss the possible effects in the fabrication of protein chips.

PMID- 23558163
TI  - Effect of lower sodium intake on health: systematic review and meta-analyses.
AB  - OBJECTIVE: To assess the effect of decreased sodium intake on blood pressure,
      related cardiovascular diseases, and potential adverse effects such as changes in
      blood lipids, catecholamine levels, and renal function. DESIGN: Systematic review
      and meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials,
      Medline, Embase, WHO International Clinical Trials Registry Platform, the Latin
      American and Caribbean health science literature database, and the reference
      lists of previous reviews. STUDY SELECTION: Randomised controlled trials and
      prospective cohort studies in non-acutely ill adults and children assessing the
      relations between sodium intake and blood pressure, renal function, blood lipids,
      and catecholamine levels, and in non-acutely ill adults all cause mortality,
      cardiovascular disease, stroke, and coronary heart disease. STUDY APPRAISAL AND
      SYNTHESIS: Potential studies were screened independently and in duplicate and
      study characteristics and outcomes extracted. When possible we conducted a meta
      analysis to estimate the effect of lower sodium intake using the inverse variance
      method and a random effects model. We present results as mean differences or risk
      ratios, with 95% confidence intervals. RESULTS: We included 14 cohort studies and
      five randomised controlled trials reporting all cause mortality, cardiovascular
      disease, stroke, or coronary heart disease; and 37 randomised controlled trials
      measuring blood pressure, renal function, blood lipids, and catecholamine levels
      in adults. Nine controlled trials and one cohort study in children reporting on
      blood pressure were also included. In adults a reduction in sodium intake
      significantly reduced resting systolic blood pressure by 3.39 mm Hg (95%
      confidence interval 2.46 to 4.31) and resting diastolic blood pressure by 1.54 mm
      Hg (0.98 to 2.11). When sodium intake was <2 g/day versus >= 2 g/day, systolic
      blood pressure was reduced by 3.47 mm Hg (0.76 to 6.18) and diastolic blood
      pressure by 1.81 mm Hg (0.54 to 3.08). Decreased sodium intake had no significant
      adverse effect on blood lipids, catecholamine levels, or renal function in adults
      (P>0.05). There were insufficient randomised controlled trials to assess the
      effects of reduced sodium intake on mortality and morbidity. The associations in
      cohort studies between sodium intake and all cause mortality, incident fatal and
      non-fatal cardiovascular disease, and coronary heart disease were non-significant
      (P>0.05). Increased sodium intake was associated with an increased risk of stroke
      (risk ratio 1.24, 95% confidence interval 1.08 to 1.43), stroke mortality (1.63,
      1.27 to 2.10), and coronary heart disease mortality (1.32, 1.13 to 1.53). In
      children, a reduction in sodium intake significantly reduced systolic blood
      pressure by 0.84 mm Hg (0.25 to 1.43) and diastolic blood pressure by 0.87 mm Hg
      (0.14 to 1.60). CONCLUSIONS: High quality evidence in non-acutely ill adults
      shows that reduced sodium intake reduces blood pressure and has no adverse effect
      on blood lipids, catecholamine levels, or renal function, and moderate quality
      evidence in children shows that a reduction in sodium intake reduces blood
      pressure. Lower sodium intake is also associated with a reduced risk of stroke
      and fatal coronary heart disease in adults. The totality of evidence suggests
      that most people will likely benefit from reducing sodium intake.

PMID- 23558164
TI  - Effect of increased potassium intake on cardiovascular risk factors and disease:
      systematic review and meta-analyses.
AB  - OBJECTIVE: To conduct a systematic review of the literature and meta-analyses to
      fill the gaps in knowledge on potassium intake and health. DATA SOURCES: Cochrane
      Central Register of Controlled Trials, Medline, Embase, WHO International
      Clinical Trials Registry Platform, Latin American and Caribbean Health Science
      Literature Database, and the reference lists of previous reviews. STUDY
      SELECTION: Randomised controlled trials and cohort studies reporting the effects
      of potassium intake on blood pressure, renal function, blood lipids,
      catecholamine concentrations, all cause mortality, cardiovascular disease,
      stroke, and coronary heart disease were included. DATA EXTRACTION AND SYNTHESIS:
      Potential studies were independently screened in duplicate, and their
      characteristics and outcomes were extracted. When possible, meta-analysis was
      done to estimate the effects (mean difference or risk ratio with 95% confidence
      interval) of higher potassium intake by using the inverse variance method and a
      random effect model. RESULTS: 22 randomised controlled trials (including 1606
      participants) reporting blood pressure, blood lipids, catecholamine
      concentrations, and renal function and 11 cohort studies (127,038 participants)
      reporting all cause mortality, cardiovascular disease, stroke, or coronary heart
      disease in adults were included in the meta-analyses. Increased potassium intake
      reduced systolic blood pressure by 3.49 (95% confidence interval 1.82 to 5.15) mm
      Hg and diastolic blood pressure by 1.96 (0.86 to 3.06) mm Hg in adults, an effect
      seen in people with hypertension but not in those without hypertension. Systolic
      blood pressure was reduced by 7.16 (1.91 to 12.41) mm Hg when the higher
      potassium intake was 90-120 mmol/day, without any dose response. Increased
      potassium intake had no significant adverse effect on renal function, blood
      lipids, or catecholamine concentrations in adults. An inverse statistically
      significant association was seen between potassium intake and risk of incident
      stroke (risk ratio 0.76, 0.66 to 0.89). Associations between potassium intake and
      incident cardiovascular disease (risk ratio 0.88, 0.70 to 1.11) or coronary heart
      disease (0.96, 0.78 to 1.19) were not statistically significant. In children,
      three controlled trials and one cohort study suggested that increased potassium
      intake reduced systolic blood pressure by a non-significant 0.28 (-0.49 to 1.05)
      mm Hg. CONCLUSIONS: High quality evidence shows that increased potassium intake
      reduces blood pressure in people with hypertension and has no adverse effect on
      blood lipid concentrations, catecholamine concentrations, or renal function in
      adults. Higher potassium intake was associated with a 24% lower risk of stroke
      (moderate quality evidence). These results suggest that increased potassium
      intake is potentially beneficial to most people without impaired renal handling
      of potassium for the prevention and control of elevated blood pressure and
      stroke.

PMID- 23558167
TI  - Health risk evaluation of whole-body vibration by ISO 2631-5 and ISO 2631-1 for
      operators of agricultural tractors and recreational vehicles.
AB  - This paper presents experimental research evaluation of the vibration exposure
      for the health risk prediction during vehicle operation. The vibration
      measurements were carried out on a recreational vehicle and two types of
      agricultural tractors. The vibration levels were measured for different surfaces
      and vehicle speed conditions. Based on the analysis of the results in the small
      agricultural tractor operated in the workplace (frameworks), Sed exceeded 0.80
      MPa by ISO2631-5:2004, and Av exceeded 0.89 m/s(2) by ISO2631-1:1997. That means
      that operators driving small agricultural tractors more than 8 h a day have a
      high probability of adverse health effects. However, the exposure value for the
      recreational vehicle had Sed < 0.5 MPa by ISO2631-5:2004 and Av < 0.5 m/s(2) by
      ISO2631-1:1997 on highways and local roads. That means Recreational Vehicle
      operators driving more than 8 h a day, have a low probability of adverse health
      effects. Also, for the recreational vehicle, vibration was taken at different
      speeds (40-60 km/h, 80 km/h, 100-120 km/h). However, the speed change did not
      appear to affect the vibration dose variation while driving a vehicle on the
      highway and road. Finally, the health effect index of ISO2631-5:2004 are almost
      the same as assessment of health effect by ISO2631-1:1997.

PMID- 23558166
TI  - Case-control study of birth characteristics and the risk of hepatoblastoma.
AB  - BACKGROUND: Hepatoblastoma is a malignant embryonal tumor typically diagnosed in
      children younger than five years of age. Little is known on hepatoblastoma
      etiology. METHODS: We matched California Cancer Registry records of
      hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to
      birth records using a probabilistic record linkage program, yielding 261 cases.
      Controls (n=218,277), frequency matched by birth year to all cancer cases in
      California for the same time period, were randomly selected from California birth
      records. We examined demographic and socioeconomic information, birth
      characteristics, pregnancy history, complications in pregnancy, labor and
      delivery, and abnormal conditions and clinical procedures relating to the
      newborn, with study data taken from birth certificates. RESULTS: We observed
      increased risks for hepatoblastoma among children with low [1500-2499 g, Odds
      Ratio (OR)=2.02, 95% confidence interval (CI) 1.29-3.15] and very low birthweight
      (<1500 g, OR=15.4, 95% CI 10.7-22.3), preterm birth <33 weeks (OR=7.27, 95% CI
      5.00, 10.6), small size for gestational age (OR=1.75, 95% CI 1.25-2.45), and with
      multiple birth pregnancies (OR=2.52, 95% CI 1.54-4.14). We observed a number of
      pregnancy and labor complications to be related to hepatoblastoma, including
      preeclampsia, premature labor, fetal distress, and congenital anomalies.
      CONCLUSION: These findings confirm previously reported associations with low
      birthweight and preeclampsia. The relation with multiple birth pregnancies has
      been previously reported and may indicate a relation to infertility treatments.

PMID- 23558168
TI  - Comprehensive temporal information detection from clinical text: medical events,
      time, and TLINK identification.
AB  - BACKGROUND: Temporal information detection systems have been developed by the
      Mayo Clinic for the 2012 i2b2 Natural Language Processing Challenge. OBJECTIVE:
      To construct automated systems for EVENT/TIMEX3 extraction and temporal link
      (TLINK) identification from clinical text. MATERIALS AND METHODS: The i2b2
      organizers provided 190 annotated discharge summaries as the training set and 120
      discharge summaries as the test set. Our Event system used a conditional random
      field classifier with a variety of features including lexical information,
      natural language elements, and medical ontology. The TIMEX3 system employed a
      rule-based method using regular expression pattern match and systematic reasoning
      to determine normalized values. The TLINK system employed both rule-based
      reasoning and machine learning. All three systems were built in an Apache
      Unstructured Information Management Architecture framework. RESULTS: Our TIMEX3
      system performed the best (F-measure of 0.900, value accuracy 0.731) among the
      challenge teams. The Event system produced an F-measure of 0.870, and the TLINK
      system an F-measure of 0.537. CONCLUSIONS: Our TIMEX3 system demonstrated good
      capability of regular expression rules to extract and normalize time information.
      Event and TLINK machine learning systems required well-defined feature sets to
      perform well. We could also leverage expert knowledge as part of the machine
      learning features to further improve TLINK identification performance.

PMID- 23558170
TI  - Neural decoding of visual imagery during sleep.
AB  - Visual imagery during sleep has long been a topic of persistent speculation, but
      its private nature has hampered objective analysis. Here we present a neural
      decoding approach in which machine-learning models predict the contents of visual
      imagery during the sleep-onset period, given measured brain activity, by
      discovering links between human functional magnetic resonance imaging patterns
      and verbal reports with the assistance of lexical and image databases. Decoding
      models trained on stimulus-induced brain activity in visual cortical areas showed
      accurate classification, detection, and identification of contents. Our findings
      demonstrate that specific visual experience during sleep is represented by brain
      activity patterns shared by stimulus perception, providing a means to uncover
      subjective contents of dreaming using objective neural measurement.

PMID- 23558171
TI  - Nuclear actin network assembly by formins regulates the SRF coactivator MAL.
AB  - Formins are potent activators of actin filament assembly in the cytoplasm. In
      turn, cytoplasmic actin polymerization can promote release of actin from
      megakaryocytic acute leukemia (MAL) protein for serum response factor (SRF)
      transcriptional activity. We found that formins polymerized actin inside the
      mammalian nucleus to drive serum-dependent MAL-SRF activity. Serum stimulated
      rapid assembly of actin filaments within the nucleus in a formin-dependent
      manner. The endogenous formin mDia was regulated with an optogenetic tool, which
      allowed for photoreactive release of nuclear formin autoinhibition. Activated
      mDia promoted rapid and reversible nuclear actin network assembly, subsequent MAL
      nuclear accumulation, and SRF activity. Thus, a dynamic polymeric actin structure
      within the nucleus is part of the serum response.

PMID- 23558169
TI  - An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma
      cells.
AB  - The recent discovery of mutations in metabolic enzymes has rekindled interest in
      harnessing the altered metabolism of cancer cells for cancer therapy. One
      potential drug target is isocitrate dehydrogenase 1 (IDH1), which is mutated in
      multiple human cancers. Here, we examine the role of mutant IDH1 in fully
      transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1
      inhibitor (AGI-5198) identified through a high-throughput screen blocked, in a
      dose-dependent manner, the ability of the mutant enzyme (mIDH1) to produce R-2
      hydroxyglutarate (R-2HG). Under conditions of near-complete R-2HG inhibition, the
      mIDH1 inhibitor induced demethylation of histone H3K9me3 and expression of genes
      associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth
      of IDH1-mutant--but not IDH1-wild-type--glioma cells without appreciable changes
      in genome-wide DNA methylation. These data suggest that mIDH1 may promote glioma
      growth through mechanisms beyond its well-characterized epigenetic effects.

PMID- 23558172
TI  - Annually resolved ice core records of tropical climate variability over the past
      ~1800 years.
AB  - Ice cores from low latitudes can provide a wealth of unique information about
      past climate in the tropics, but they are difficult to recover and few exist.
      Here, we report annually resolved ice core records from the Quelccaya ice cap
      (5670 meters above sea level) in Peru that extend back ~1800 years and provide a
      high-resolution record of climate variability there. Oxygen isotopic ratios
      (delta(18)O) are linked to sea surface temperatures in the tropical eastern
      Pacific, whereas concentrations of ammonium and nitrate document the dominant
      role played by the migration of the Intertropical Convergence Zone in the region
      of the tropical Andes. Quelccaya continues to retreat and thin. Radiocarbon dates
      on wetland plants exposed along its retreating margins indicate that it has not
      been smaller for at least six millennia.

PMID- 23558173
TI  - Targeted inhibition of mutant IDH2 in leukemia cells induces cellular
      differentiation.
AB  - A number of human cancers harbor somatic point mutations in the genes encoding
      isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). These mutations alter residues
      in the enzyme active sites and confer a gain-of-function in cancer cells,
      resulting in the accumulation and secretion of the oncometabolite (R)-2
      hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently
      and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal
      structure of AGI-6780 complexed with IDH2/R140Q revealed that the inhibitor binds
      in an allosteric manner at the dimer interface. The results of steady-state
      enzymology analysis were consistent with allostery and slow-tight binding by AGI
      6780. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and
      primary human acute myelogenous leukemia cells in vitro. These data provide proof
      of-concept that inhibitors targeting mutant IDH2/R140Q could have potential
      applications as a differentiation therapy for cancer.

PMID- 23558174
TI  - Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide
      alkyne cycloadditions.
AB  - Copper(I)-catalyzed azide-alkyne cycloaddition has become a commonly employed
      method for the synthesis of complex molecular architectures under challenging
      conditions. Despite the widespread use of copper-catalyzed cycloaddition
      reactions, the mechanism of these processes has remained difficult to establish
      due to the involvement of multiple equilibria between several reactive
      intermediates. Real-time monitoring of a representative cycloaddition process via
      heat-flow reaction calorimetry revealed that monomeric copper acetylide complexes
      are not reactive toward organic azides unless an exogenous copper catalyst is
      added. Furthermore, crossover experiments with an isotopically enriched exogenous
      copper source illustrated the stepwise nature of the carbon-nitrogen bond-forming
      events and the equivalence of the two copper atoms within the cycloaddition
      steps.

PMID- 23558176
TI  - Behavioral testing regimens in genetic-based animal models of Parkinson's
      disease: cogencies and caveats.
AB  - Although the onset and progression of Parkinson's disease (PD) is fundamentally
      sporadic, identification of several of the genes implicated in the disease has
      provided significant insight concerning patho-physiological mechanisms
      potentially underlying sporadic PD. Moreover, such studies have caused a
      revolution in the way researchers view the disease. Since single genes
      responsible for rare familial forms of the disease have only been identified
      within the past few years, animal models based on these defects have only
      recently been generated, thereby not leaving a lot of time for their evaluation
      and subsequent improvement. The current article provides an extensive review of
      the major motor and non-motor behavioral tests used in genetically-induced
      Parkinsonian animals. Moreover, we assess the insights concerning the
      etiopathogenesis of PD generated from use of such tests and how these have
      improved available treatment strategies for alleviating aspects of sporadic and
      non-sporadic parkinsonism.

PMID- 23558177
TI  - Case scenario: Hemodynamic management of postoperative acute kidney injury.

PMID- 23558175
TI  - Research resource: identification of novel coregulators specific for thyroid
      hormone receptor-beta2.
AB  - Thyroid hormone receptors (TRs) are expressed as a series of interrelated
      isoforms that perform distinct biological roles. The TRbeta2 isoform is found
      predominantly in the hypothalamus, pituitary, retina, and cochlea and displays
      unique transcriptional properties relative to the other TR isoforms. To more
      fully understand the isoform-specific biological and molecular properties of
      TRbeta2, we have identified a series of previously unrecognized proteins that
      selectively interact with TRbeta2 compared with the more widely expressed
      TRbeta1. Several of these proteins preferentially enhance the transcriptional
      activity of TRbeta2 when coexpressed in cells and are likely to represent novel,
      isoform-specific coactivators. Additional proteins were also identified in our
      screen that bind equally to TRbeta1 and TRbeta2 and may function as isoform
      independent auxiliary proteins for these and/or other nuclear receptors. We
      propose that a combination of isoform-specific recruitment and tissue-specific
      expression of these newly identified coregulator candidates serves to customize
      TR function for different biological purposes in different cell types.

PMID- 23558178
TI  - Successful cardiopulmonary resuscitation in the lateral position during
      intraoperative cardiac arrest.

PMID- 23558181
TI  - Immobilized keratinase and enrofloxacin loaded on pectin PVA cryogel patches for
      antimicrobial treatment.
AB  - A keratinase isolated from Paecilomyces lilacinus (LPS #876) was tested against
      proteins present in the skin but the high enzyme activity was detected on
      collagen. Keratinase was physically immobilized onto PVA-pectin cryogels and
      enzyme release was 20.8+/-2.1%, 63.8+/-0.2%, 41.5+/-3.5% and 26.0+/-3.5% in
      cryogels containing pectins with esterification degrees (DE) 33.0%, 55.0%, 62.7%
      and 71.7% respectively at 37 degrees C after 3h incubation. In presence of 0.75 M
      NaCl, the percentage of enzyme release changed to: 57.5+/-1.5, 65.8+/-3.8, 57.3+/
      0.2 and 34.0+/-4.0 for the four pectins respectively. In-vitro studies of
      enrofloxacin release from PVA-pectin cryogels at pH close to the human skin
      (pH=5.5) showed 15.0% free antibiotic following first order kinetic at 37 degrees
      C after 5h incubation. However, in the presence of keratinase only 6.9% of
      enrofloxacin was released under the same experimental conditions.

PMID- 23558179
TI  - Presynaptic gating of postsynaptic synaptic plasticity: a plasticity filter in
      the adult auditory cortex.
AB  - Sensory cortices can not only detect and analyze incoming sensory information but
      can also undergo plastic changes while learning behaviorally important sensory
      cues. This experience-dependent cortical plasticity is essential for shaping and
      modifying neuronal circuits to perform computations of multiple, previously
      unknown sensations, the adaptive process that is believed to underlie perceptual
      learning. Intensive efforts to identify the mechanisms of cortical plasticity
      have provided several important clues; however, the exact cellular sites and
      mechanisms within the intricate neuronal networks that underlie cortical
      plasticity have yet to be elucidated. In this review, we present several
      parallels between cortical plasticity in the auditory cortex and recently
      discovered mechanisms of synaptic plasticity gating at thalamocortical
      projections that provide the main input to sensory cortices. Striking
      similarities between the features and mechanisms of thalamocortical synaptic
      plasticity and those of experience-dependent cortical plasticity in the auditory
      cortex, especially in terms of regulation of an early critical period, point to
      thalamocortical projections as an important locus of plasticity in sensory
      cortices. 

PMID- 23558183
TI  - Transesterification of rapeseed oil for biodiesel production in trickle-bed
      reactors packed with heterogeneous Ca/Al composite oxide-based alkaline catalyst.
AB  - A conventional trickle bed reactor and its modified type both packed with Ca/Al
      composite oxide-based alkaline catalysts were studied for biodiesel production by
      transesterification of rapeseed oil and methanol. The effects of the methanol
      usage and oil flow rate on the FAME yield were investigated under the normal
      pressure and methanol boiling state. The oil flow rate had a significant effect
      on the FAME yield for the both reactors. The modified trickle bed reactor kept
      over 94.5% FAME yield under 0.6 mL/min oil flow rate and 91 mL catalyst bed
      volume, showing a much higher conversion and operational stability than the
      conventional type. With the modified trickle bed reactor, both
      transesterification and methanol separation could be performed simultaneously,
      and glycerin and methyl esters were separated additionally by gravity separation.

PMID- 23558182
TI  - Electron acceptor dependence of electron shuttle secretion and extracellular
      electron transfer by Shewanella oneidensis MR-1.
AB  - Shewanella oneidensis MR-1 is an extensively studied dissimilatory metal-reducing
      bacterium with a great potential for bioremediation and electricity generation.
      It secretes flavins as electron shuttles which play an important role in
      extracellular electron transfer. However, the influence of various environmental
      factors on the secretion of flavins is largely unknown. Here, the effects of
      electron acceptors, including fumarate, ferrihydrite, Fe(III)-nitrilotriacetic
      acid (NTA), nitrate and trimethylamine oxide (TMAO), on the secretion of flavins
      were investigated. The level of riboflavin and riboflavin-5'-phosphate (FMN)
      secreted by S. oneidensis MR-1 varied considerably with different electron
      acceptors. While nitrate and ferrihydrite suppressed the secretion of flavins in
      relative to fumarate, Fe(III)-NTA and TMAO promoted such a secretion and greatly
      enhanced ferrihydrite reduction and electricity generation. This work clearly
      demonstrates that electron acceptors could considerably affect the secretion of
      flavins and consequent microbial EET. Such impacts of electron acceptors in the
      environment deserve more attention.

PMID- 23558184
TI  - Effect of shear rate on the response of microbial fuel cell toxicity sensor to
      Cu(II).
AB  - A microbial fuel cell (MFC) was successfully developed as a toxicity
      biomonitoring system, giving a quick response to Cu(II) toxic events. The
      objective was to increase MFC sensitivity to Cu(II) toxicity by evaluating the
      impact of shear rate caused by mixing and intermittent nitrogen sparging on the
      biofilm structure. Low shear rate - achieved by continuously feeding the
      wastewater into the MFC at a low flow rate of 1.3 mL min(-1) during the
      enrichment period - resulted in low biomass density (124 g VSS L(-1) of biofilm),
      high porosity and reduced levels of extracellular polymeric substances (EPS).
      Consequently, the sensitivity was improved. Scattered nitrogen sparging also
      increased the sensitivity by reducing the EPS level. It suggested that MFC
      enriched under low flow rate with intermittent nitrogen sparging could produce an
      anodic biofilm that was less dense, more porous, contained less EPS and
      ultimately displayed higher sensitivity to Cu(II) toxicity.

PMID- 23558186
TI  - Comparison of rapid cultural methods for the detection of Salmonella species.
AB  - Three newly developed rapid cultural methods (Rapid Salmonella, PrecisTM
      Salmonella, IBISA Salmonella) for the detection of Salmonella spp. were compared
      to a reference method. All methods performed comparably on
      inclusivity/exclusivity testing. Similar limits of detection were observed for
      all methods with milk, cocoa and bouillon matrices. Some tea varieties appeared
      to disturb the normal color formation of all selective agars tested.

PMID- 23558185
TI  - Succinic acid production by Actinobacillus succinogenes NJ113 using corn steep
      liquor powder as nitrogen source.
AB  - In this study, corn steep liquor powder (CSL) was used as nitrogen source to
      replace the relatively costly yeast extract typically used for the production of
      succinic acid with Actinobacillus succinogenes NJ113. Moreover, when heme was
      added to the fermentation medium and the culture was agitated at a low speed, a
      maximum succinic acid concentration of 37.9 g/l was obtained from a glucose
      concentration of 50 g/l, and a productivity of 0.75 g/l/h was achieved. These
      yields are almost as high as for fermentation with glucose and yeast extract.
      These results suggest that heme-supplemented CSL may be a suitable alternative
      nitrogen source for a cost-effective method of producing succinic acid with A.
      succinogenes NJ113 while consuming less energy than previous methods.

PMID- 23558187
TI  - Listeria monocytogenes dairy isolates show a different proteome response to
      sequential exposure to gastric and intestinal fluids.
AB  - The gastrointestinal system poses different stresses to the foodborne pathogen,
      Listeria monocytogenes, including the low pH of the stomach and the presence of
      bile and the high osmolality of the intestinal fluid. The present study evaluated
      how previous exposure of three L. monocytogenes dairy isolates (C882 and T8,
      serovar 4b isolates and A9 serovar 1/2a or 3b isolate) to a cheese-simulated
      medium (p H5.5 and 3.5% NaCl [w/v], adapted cultures) affected subsequent
      survival in a simulated gastrointestinal system. Listerial cultures exposed to
      the cheese-simulated medium at pH7.0, with no added NaCl, were considered non
      adapted. To investigate the main events involved in listerial survival during the
      gastric and intestinal subsequent challenge, a proteomic approach was used. All
      L. monocytogenes strains were able to survive the deleterious effects of the
      gastrointestinal fluids and no significant differences were observed between
      adapted and non-adapted cells. However the L. monocytogenes strains showed a
      different protein pattern in response to the gastrointestinal stress. Data
      indicated that synthesis of stress related proteins is more pronounced in non
      adapted cells. Although, a significant number of enzymes involved in glycolysis
      and energy production were also consistently over-produced by the three strains.
      These findings provided new insights into the means used by L. monocytogenes to
      overcome the gastrointestinal system and allow the pathogen to move to the next
      phase of the infectious process.

PMID- 23558188
TI  - Porosity of Lactococcus lactis subsp. lactis LD61 colonies immobilised in model
      cheese.
AB  - During cheese ripening, micro-organisms grow as immobilised colonies,
      metabolising substrates present in the matrix which generate products triggered
      by enzymatic reactions. Local limitation rates of diffusion, either in the matrix
      or within the bacterial colonies, can be responsible for modulation in the
      metabolic and enzymatic activities of micro-organisms during ripening. How
      bacterial colonies immobilised in cheese are porous to these diffusing solutes
      has never been explored. The objective of this study was to determine if
      fluorescent dextrans of different sizes (4.4, 70 and 155 kDa) are able to
      penetrate through colonies of Lactococcus lactis LD61 immobilised in solid media,
      either agar or model cheese. Confocal microscopic observations showed that
      lactococcus colonies immobilised in these two media were porous to dextrans from
      4 kDa to 155 kDa. However, the rate of diffusion of the solutes was faster inside
      the colonies immobilised in ultrafiltered-cheese than in agar when large dextrans
      were considered (>=70 kDa). The colonial shape of the lactococcus strain was also
      shown to be lenticular in agar and spherical in the model cheese, indicating that
      the physical pressure exerted on the colony by the surrounding casein network was
      probably isotropous in the UF-cheese but not in agar. In both cases, the fact
      that lactococcus colonies immobilised in solid media are porous to large dextran
      solutes suggests that substrates or enzymes are likely also to be able to migrate
      inside the colonies during cheese ripening.

PMID- 23558189
TI  - The lactic acid bacteria and yeast microbiota of eighteen sourdoughs used for the
      manufacture of traditional Italian sweet leavened baked goods.
AB  - The lactic acid bacteria and yeast microbiota of eighteen sourdoughs used for the
      manufacture of some traditional Italian sweet leavened baked goods were studied
      through culture-dependent method and pyrosequencing. Flours used for back
      slopping and sourdoughs were also biochemically characterized. Principal
      component analysis was applied to explore eventual correlations between process
      parameters applied during back slopping, some flour nutrients, profile of
      microbiota, and biochemical characteristics of sourdoughs. The median values of
      the cell density of lactic acid bacteria and yeasts were 8.05 and 7.03 log CFU/g,
      respectively. As shown by culture-dependent method, Lactobacillus
      sanfranciscensis was identified in all the sourdoughs, except for Panaredda and
      Torcolo di San Costanzo. For eleven sourdoughs, all the lactic acid bacteria
      isolates were allotted to this species. For Buccellato di Lucca, Mbriagotto,
      Pandoro, and Nadalin sourdoughs, at least 80% of the isolates was allotted to
      this species. Other lactic acid bacteria isolated with a relatively high
      frequence were Lactobacillus plantarum and Leuconostoc citreum. Pyrosequencing
      confirmed and complemented the culture-dependent approach, detecting L.
      sanfranciscensis also in Panaredda and Torcolo di San Costanzo sourdoughs.
      Saccharomyces cerevisiae was identified in all the sourdoughs, except for
      Mbriagotto, Ciambella di Mosto and Pandolce Genovese. These latter sourdoughs
      harbored strains of Candida humilis, whereas five sourdoughs combined the
      presence of both yeast species. Positive correlations were found between time of
      back slopping and cell density and main metabolites of lactic acid bacteria.
      Percentage of sourdough used as inoculum was mainly correlated with the cell
      density of yeasts and the concentration of ethanol. This study provided a
      comprehensive and comparative approach to highlight the dominant microbiota of
      Italian sourdoughs, which could be exploited further to guarantee a highly
      reproducible quality of the Italian sweet goods studied, while preserving their
      traditional trait.

PMID- 23558190
TI  - Characterisation of commercial and natural Torulaspora delbrueckii wine yeast
      strains.
AB  - Forty-three South African Torulaspora delbrueckii yeast isolates from the ARC
      Infruitec-Nietvoorbij yeast culture collection, the T. delbrueckii type strain
      (CBS 1146), one reference T. delbrueckii strain (CBS 4663), two T. delbrueckii
      strains isolated from commercial yeast blends (Viniflora(r) Harmony.nsac and
      Viniflora(r) Melody.nsac), and a commercial Saccharomyces cerevisiae yeast (VIN
      13) had their identities confirmed and were characterised using conventional and
      molecular microbiological techniques. These included a selection of growth media
      as well as CHEF electrophoretic karyotyping and PCR-RFLP analyses. Based on the
      biochemical and physiological results the strains were divided into 13 groups.
      The performances of the yeasts were also monitored by means of laboratory-scale
      fermentations in grape must at 15  degrees C and 22  degrees C. The fermentation
      kinetic data showed that at 22  degrees C, the yeasts were divided into two
      distinct groups, a faster and a slower fermenting group. The fermentation curves
      of the laboratory-scale study at 15  degrees C showed that, at this lower
      temperature, the yeasts also fermented at different speeds, but the fermentation
      curves showed greater separation. The biochemical and physiological grouping did
      not coincide with the fermentation abilities and good fermenters could be found
      in more than one group. Chemical analyses of the resultant wines (alcohol,
      volatile acidity, glycerol, total SO2, residual sugar) were used in Principle
      Component Analyses. The yeasts that grouped close to the S. cerevisiae reference
      strain (VIN 13) showed more acceptable wine chemical profiles, while those
      further away displayed less acceptable profiles. Three locally isolated strains
      and one commercial T. delbrueckii yeast strain, Viniflora(r) Harmony.nsac.
      produced wines with acceptable chemical profiles at both temperatures. These
      strains also had comparable fermentation kinetics to the S. cerevisiae reference.
      Therefore, depending on the fermentation temperature, different T. delbrueckii
      strains will be suitable for specific wine styles and some may even be considered
      for single inoculations without S. cerevisiae in industrial fermentations.

PMID- 23558191
TI  - Antimicrobial resistance of Enterococcus species from meat and fermented meat
      products isolated by a PCR-based rapid screening method.
AB  - Enterococci are predominantly found in the gastrointestinal tract of humans and
      animals, but species commonly resident on vegetation are known. Their presence in
      large numbers in foods may indicate a lapse in sanitation and their ability to
      serve as a genetic reservoir of transferable antibiotic resistance is of concern.
      Conventional culture methods for identification of enterococci are slow and
      sometimes give false results because of the biochemical diversity of the
      organisms in this genus. This work reports the development of a PCR-based assay
      to detect enterococci at the genus level by targeting a 16S rRNA sequence.
      Published 16S rRNA sequences were aligned and used to design genus specific
      primers (EntF and EntR). The primers were able to amplify a 678 bp target region
      from Enterococcus faecalis ATCC 7080 and 20 other strains of enterococci from 11
      different species, but there was no amplification by 32 species from closely
      related genera (Pediococcus, Lactobacillus, Streptococcus and Listeria) or
      species of Escherichia coli and Salmonella. The PCR positive samples were plated,
      screened by a colony patch technique and their identities were confirmed by API
      20 Strep panels and sequencing. When dry fermented sausage and ham as well as
      fresh meat batter for dry cured sausage manufacture were tested for enterococci
      by the method, 29 Enterococcus strains (15 E. faecalis, 13 E. faecium, and one E.
      gallinarum) were identified. When susceptibility of these enterococci to 12
      antibiotics was tested, the highest incidence of resistance was to clindamycin
      (89.6%), followed by tetracycline hydrochloride (65.5%), tylosin (62%),
      erythromycin (45%), streptomycin and neomycin (17%), chloramphenicol (10.3%),
      penicillin (10.3%), ciprofloxacin (10.3%) and gentamicin (3.4%). None was
      resistant to the clinically important drugs vancomycin or ampicillin. Most
      strains (27/29) were resistant to more than one antibiotic while 17 of 29 strains
      were resistant to three to 8 antibiotics. The molecular method developed was
      validated for speciation of enterococci and was useful in assessing uncooked
      processed meat products as a reservoir for multi-drug resistant Enterococcus
      species.

PMID- 23558192
TI  - Combined treatments of enterocin AS-48 with biocides to improve the inactivation
      of methicillin-sensitive and methicillin-resistant Staphylococcus aureus
      planktonic and sessile cells.
AB  - Control of staphylococci during cleaning and disinfection is important to the
      food industry. Broad-spectrum bacteriocins with proved anti-staphylococcal
      activity, such as enterocin AS-48, could open new possibilities for disinfection
      in combination with biocides. In the present study, enterocin AS-48 was tested
      singly or in combination with biocides against a cocktail of six Staphylococcus
      aureus strains (including three methicillin-resistant strains) in planktonic
      state as well as in biofilms formed on polystyrene microtiter plates. Cells were
      challenged with enterocin, biocides or enterocin/biocide combinations.
      Inactivation of planktonic cells increased significantly (p<0.05) when enterocin
      AS-48 (25mg/l) was tested in combination with benzalkonium chloride (BC),
      cetrimide (CT) and hexadecylpyridinium chloride (HDP), and non-significantly in
      combination with didecyldimethylammonium bromide (AB), triclosan (TC),
      hexachlorophene (CF), polyhexamethylen guanidinium chloride (PHMG), chlorhexidine
      (CH) or P3-oxonia (OX). In the sessile state (24h biofilms), staphylococci
      required higher biocide concentrations in most cases, except for OX. Inactivation
      of sessile staphylococci increased remarkably when biocides were applied in
      combination with enterocin AS-48, especially when the bacteriocin was added at
      50mg/l. During storage, the concentrations of sessile as well as planktonic cells
      in the treated samples decreased remarkably for BC, TC and PHMG, but OX failed to
      inhibit proliferation of the treated biofilms as well as growth of planktonic
      cells. The observed inhibitory effects during storage were potentiated when the
      biocides were combined with 50 mg/l enterocin AS-48. Results from this study
      suggest that selected combinations of enterocin AS-48 and biocides offer
      potential use against planktonic and sessile, methicillin-sensitive and
      methicillin-resistant S. aureus.

PMID- 23558193
TI  - Modelling the effect of chilling on the occurrence of Salmonella on pig carcasses
      at study, abattoir and batch levels by meta-analysis.
AB  - The effect of chilling on the occurrence of Salmonella on pig carcasses was
      investigated at study, abattoir and batch level by meta-analysis. Both the fixed
      effects and random-effects model confirmed (p<0.05) the significant effect of
      chilling in decreasing Salmonella occurrence on pig carcasses; although the
      random-effects solution was preferred to account for the significant variability
      in effect size (p<0.001) estimated from the 13 primary studies considered, the 32
      abattoirs surveyed, and the 51 sampled batches. Conservatively, it can be said
      that chilling reduces the Salmonella incidence on pig carcasses by a mean ratio
      of ~1.6 (95% CI: 1.0-2.6). Multilevel meta-analysis models investigating study
      characteristics that could explain the heterogeneity (tau(2)) in the true effect
      size among primary studies (tau(2)=0.578), among surveyed abattoirs
      (tau(2)=0.431), and among sampled batches (tau(2)=0.373), revealed that study
      size (represented by the moderating variables of 'total sample size' and 'number
      of batches sampled in an abattoir') and 'carcass swabbed area' have a significant
      impact (p<0.05) on the measured effect size of chilling. The fact that swabbed
      area explained between 56 and 62% and total sample size between 23 and 38% of the
      total heterogeneity in the chilling true effect size, indicates that differences
      in experimental design greatly affect our substantive conclusion about the effect
      of chilling on Salmonella occurrence. This inconsistency to elucidate the effect
      of chilling arises because of the many factors influencing both the performance
      of the chilling operation and the measurement itself. Meta-analysis was not only
      instrumental to show that small-size studies (i.e., only one batch sampled per
      abattoir, total number of sampled carcasses per batch<50) and small swabbed areas
      (<100 cm(2)) lead to imprecise and even conflicting conclusions, but most
      importantly, enabled definition of the characteristics of a well-designed study
      having a minimum statistical power to produce precise results. A sound
      experimental design derived by multilevel meta-analysis consists of swabbing
      carcass areas of at least 500 cm(2) from 25 pre-chill and 25 post-chill carcasses
      from a single production batch, with a minimum of two batches sampled per
      surveyed abattoir. If the survey were to be conducted in more than one abattoir,
      the total sample size should not be less than 400. Two methods to test for
      publication bias, a common problem in meta-analysis, suggested that whilst the
      presence of unpublished small-size studies is probable, it is not likely that
      this would significantly bias the overall chilling effect estimated in this
      study.

PMID- 23558194
TI  - Inactivation of Listeria monocytogenes on frankfurters by plant-derived
      antimicrobials alone or in combination with hydrogen peroxide.
AB  - Listeria monocytogenes is a significant foodborne pathogen associated with
      outbreaks involving contaminated ready-to-eat (RTE) products, including
      frankfurters. The USDA-FSIS has established a zero tolerance policy for L.
      monocytogenes in RTE products, thereby warranting effective post-processing
      interventions to control the pathogen on these foods. In the present study, the
      antilisterial activity of GRAS (generally recognized as safe)-status plant
      derived antimicrobials (PDAs), namely beta-resorcylic acid (BR), carvacrol (CR),
      and trans-cinnamaldehyde (TC) either alone or in combination with hydrogen
      peroxide (HP) as post-processing dip treatments on frankfurters was investigated.
      Frankfurters were surface inoculated with a five-strain mixture of L.
      monocytogenes (~6.0 log CFU per frankfurter), followed by dip treatment at 55 
      degrees C for 60s or 65  degrees C for 30s in sterile deionized water, or water
      containing BR (1.5%), CR (0.75%), or TC (0.75%) either alone or in combination
      with HP (0.1%). Treated frankfurters were vacuum-packaged, and stored at 4 
      degrees C for 70 days. Representative samples were analyzed on days 0, 1, 3, 7,
      14, 28, 42, 56, and 70 of refrigerated storage for enumerating surviving L.
      monocytogenes on frankfurters. Six frankfurters were sampled at each time point
      for each treatment. On day zero, all PDAs reduced L. monocytogenes counts by >2
      log CFU/frankfurter at both temperatures (P<0.05), compared to controls. From
      days 1 to 70, L. monocytogenes counts on PDA-treated frankfurters were
      consistently lower (P<0.05) and after 70 days of storage, the pathogen counts
      were reduced to undetectable levels on frankfurters treated with PDA-HP
      combinations at 65  degrees C, and by combinations of BR and TC with HP at 55 
      degrees C. Results suggest that PDAs alone, or in combination with HP could be
      effectively used as post-processing dips to reduce L. monocytogenes on
      frankfurters, although follow-up studies on sensory and quality characteristics
      of PDA-treated frankfurters are necessary.

PMID- 23558195
TI  - Impacts of climate change on the microbial safety of pre-harvest leafy green
      vegetables as indicated by Escherichia coli O157 and Salmonella spp.
AB  - The likelihood of leafy green vegetable (LGV) contamination and the associated
      pathogen growth and survival are strongly related to climatic conditions.
      Particularly temperature increase and precipitation pattern changes have a close
      relationship not only with the fate and transport of enteric bacteria, but also
      with their growth and survival. Using all relevant literature, this study reviews
      and synthesises major impacts of climate change (temperature increases and
      precipitation pattern changes) on contamination sources (manure, soil, surface
      water, sewage and wildlife) and pathways of foodborne pathogens (focussing on
      Escherichia coli O157 and Salmonella spp.) on pre-harvested LGVs. Whether climate
      change increases their prevalence depends not only on the resulting local balance
      of the positive and negative impacts but also on the selected regional climate
      change scenarios. However, the contamination risks are likely to increase. This
      review shows the need for quantitative modelling approaches with scenario
      analyses and additional laboratory experiments. This study gives an extensive
      overview of the impacts of climate change on the contamination of pre-harvested
      LGVs and shows that climate change should not be ignored in food safety
      management and research.

PMID- 23558196
TI  - Lipolysis within single culture and co-culture biofilms of dairy origin.
AB  - Bacteria in raw milk can produce heat-stable lipases, which survive
      pasteurisation and subsequently reduce the shelf life of dairy products because
      of their ability to break down the milk fat and increase rancidity. In this
      study, four bacteria, originating from the surfaces of raw milk transport
      tankers, and a known lipase-producing bacterium were evaluated for their ability
      to produce lipolysis in planktonic and biofilm cultures. Lipolysis was determined
      using two separate assays that measured hydrolysis of the ester p-nitrophenol
      palmitate (pnpp) and the lipid tributyrin. The hydrolysis of pnpp per CFU within
      biofilms and planktonic cultures ranged from 0.01 to 8.35 and 0.01 to 0.07 nU/CFU
      respectively. The amount of butyric acid released from hydrolysis of tributyrin
      per CFU within biofilms and planktonic cultures ranged from 0.1 to 1110.3 and 0.1
      to 0.3 ng/CFU, respectively. The hydrolysis of pnpp and tributyrin per CFU within
      biofilms was at least 10 times higher compared with the corresponding planktonic
      cultures. This is the first study to show that lipolysis occurs within biofilms
      of bacteria that were originally isolated from the surfaces of raw milk tankers.
      This is relevant to the dairy industry, highlighting the importance of
      eliminating biofilms on milk tanker surfaces as a source of heat-stable lipases.

PMID- 23558197
TI  - Characterization of functional, safety, and gut survival related characteristics
      of Lactobacillus strains isolated from farmhouse goat's milk cheeses.
AB  - A set of 80 Lactobacillus strains (36 Lactobacillus plantarum and 44
      Lactobacillus paracasei) isolated from Spanish farmhouse cheeses have been
      studied as to their functional and safety properties and their survival under gut
      related conditions. None of these 80 Lactobacillus strains were able to hydrolyse
      starch. A high percentage of L. plantarum and L. paracasei strains were, however,
      capable of hydrolysing casein (86.1% and 68.2% respectively). For the other
      characteristics investigated, L. plantarum strains generally had more positive
      responses than L. paracasei. The latter strains tested negative for most of these
      characteristics, with the exception of stachyose hydrolysis, which was positive
      in six strains of L. paracasei. A high percentage (91.7%) of L. plantarum
      produced haemo-dependent catalase. Phytase was present in 10 L. plantarum and in
      2 L. paracasei. Most L. plantarum (83.3%) but no L. paracasei hydrolysed bile
      salts. All strains were completely resistant to a challenge of pH3, but many
      showed a loss of viability after a subsequent exposure to 0.3% oxgall; in fact,
      only one L. paracasei strain and 33 L. plantarum strains (91.67%) were tolerant
      to both stresses. L. plantarum Mb25 and L. plantarum Mb26 were the most adherent
      to Caco-2 cells (adherence percentages of 36 and 7% respectively). These two
      strains were also the most adherent to HeLa 229 cells, with 19.3 and 16.0%
      adhesion respectively. The Mb26 strain inhibited the adhesion of Listeria
      monocytogenes to Caco-2 cells when added simultaneously to Listeria and also when
      added 1h before the pathogen (21.0% and 51.6% adhesion inhibition, respectively).
      Production of H2O2 was detected in 38.9% of L. plantarum strains and in 9.1% of
      L. paracasei. Twelve L. plantarum and eight L. paracasei strains produced
      bacteriocin-like inhibitors. PCR amplifications of several plantaricin genes
      suggest that all the bacteriocinogenic strains may produce plantaricin E/F and
      some may also manufacture the plantaricin J/K. The nine L. plantarum strains
      assayed for antibiotic resistance were resistant to ciprofloxacin (MIC>2 MUg/ml),
      vancomycin (MIC>16 MUg/ml), and teicoplanin (MIC>16 MUg/ml). Moreover, some
      strains showed intermediate resistance to penicillin, tetracycline, rifampicin,
      and levofloxacin. We conclude that farmhouse cheeses are good sources of
      biotechnologically relevant lactobacilli and that the L. plantarum species shows
      better biotechnological properties than L. paracasei. This can be deduced from
      the finding of a high percentage of strains of L. plantarum that exhibit
      remarkable functional and inhibitory properties and high abilities to survive in
      gut-related conditions, which can be further developed for biotechnological
      applications.

PMID- 23558198
TI  - Esterase activity of lactic acid bacteria isolated from malolactic fermentation
      of red wines.
AB  - The goal of this study was to examine the esterase activity of 243 lactic acid
      bacteria (LAB) strains from wines of different red grape varieties, belonging to
      the genera Oenococcus, Lactobacillus, Pediococcus and Enterococcus. p-Nitrophenyl
      octanoate was used as substrate. All strains presented esterase activity in the
      first screening, but only those showing higher activity were used in subsequent
      studies to determine the cellular location of this activity, the influence of pH,
      temperature and the presence of ethanol and the substrate specificity. For the
      thirteen selected strains, the highest activity was observed in the intracellular
      fraction. Responses to pH, temperature and ethanol were strain-dependent, but for
      all the strains, a marked decrease in activity in presence of ethanol was
      observed. When the influence of pH and ethanol acting together was studied at 25 
      degrees C and 37  degrees C, temperature-dependent differences were not observed
      for any of the strains except for Oen6. In the substrate specificity assay, the
      majority of strains of all genera displayed a trend to more readily hydrolyse
      ester substrates from C8 and longer.

PMID- 23558199
TI  - Effects of Zataria multiflora Boiss. essential oil on growth and gene expression
      of enterotoxins A, C and E in Staphylococcus aureus ATCC 29213.
AB  - Staphylococcal food poisoning results from the consumption of food in which
      enterotoxigenic staphylococci have grown and produced toxins. The present study
      was conducted with three principal aims: i) to determine the minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) of Zataria
      multiflora Boiss. essential oil (EO) against Staphylococcus aureus ATCC 29213,
      ii) to evaluate the effect of subinhibitory concentrations (subMIC) of EO on the
      growth of bacteria over 72 h (at 25 and 35  degrees C), and iii) to investigate
      the expression of genes involved in the production of staphylococcal enterotoxins
      SEA, SEC and SEE over 72 h at 35  degrees C. The MIC and MBC of Z. multiflora
      Boiss. EO were 0.03 and 0.04%, respectively. Colony counting at 24, 48 and 72 h
      of 3 day cultures grown in the presence of 75%MIC of the EO showed that the
      growth rate was reduced 2.16, 2.78 and 2.91 log 10 cfu/ml at 25  degrees C, and
      1.34, 2.35 and 2.57 log 10 cfu/ml at 35  degrees C, respectively, compared to
      control cultures. SubMIC levels of EO also significantly decreased the expression
      of staphylococcal enterotoxin (SE)-related genes and therefore the production of
      SEs in a dose dependent manner. For example, when cultured with 75% MIC, the
      transcriptional levels of sea, sec, see and agrA were decreased 11.7, 9.3, 10.45
      and 10.3 fold after 18 h and 13.9, 11.21, 12.44 and 12.52 fold after 72 h in
      comparison to control, respectively.

PMID- 23558200
TI  - Increase in antioxidant and antihypertensive peptides from Argentinean wines by
      Oenococcus oeni.
AB  - Cells from an exponential Oenococcus oeni m1 culture in a grape juice medium were
      inoculated into a synthetic wine medium (SW) supplemented with a protein and
      polypeptide fraction (PPF) of high molecular weight (higher than 12,400 Da)
      obtained from four varietals of Cafayate Argentinean wines. O. oeni maintains
      viability after 48 h incubation time and enables the increase in extracellular
      proteolytic activity and the release of low molecular weight peptides by 1.067,
      0.397, 0.915 and 0.705 mg N/L in the respective SW supplemented with PPF from
      Cabernet Sauvignon, Malbec, Tannat and Torrontes wine varietals. After 48 h
      incubation time, concomitantly with peptide release, an increase in antioxidant
      and antihypertensive activities was detected in all studied media. The highest
      increase was detected in the presence of PPF from Cabernet and Tannat wine
      varietals. Maximum increase in antioxidant activity (366.1 MUmol FeSO4/L in the
      case of ferric reducing antioxidant power and 8.9% in 2,2-diphenyl-1
      picrylhydrazyl radical scavenging) was produced by the peptides released from PPF
      of Cabernet Sauvignon wine. The peptides released from PPF Tannat wine varietal
      caused the highest increase in antihypertensive activity (56.2% in angiotensin I
      converting enzyme inhibitory activity). Oenococcus oeni m1 would provide
      additional benefits to wine such as an increase in bioactive peptides with
      multifunctional beneficial activities.

PMID- 23558201
TI  - Metatranscriptomic analysis of lactic acid bacterial gene expression during
      kimchi fermentation.
AB  - Barcode-based 16S rRNA gene pyrosequencing showed that the kimchi microbiome was
      dominated by six lactic acid bacteria (LAB), Leuconostoc (Lc.) mesenteroides,
      Lactobacillus (Lb.) sakei, Weissella (W.) koreensis, Lc. gelidum, Lc. carnosum,
      and Lc. gasicomitatum. Therefore, we used completed genome sequences of
      representatives of these bacteria to investigate metatranscriptomic gene
      expression profiles during kimchi fermentation. Total mRNA was extracted from
      kimchi samples taken at five time points during a 29 day-fermentation. Nearly all
      (97.7%) of the metagenome sequences that were recruited on all LAB genomes of
      GenBank mapped onto the six LAB strains; this high coverage rate indicated that
      this approach for assessing processes carried out by the kimchi microbiome was
      valid. Expressed mRNA sequences (as cDNA) were determined using Illumina GA IIx.
      Assignment of mRNA sequences to metabolic genes using MG-RAST revealed the
      prevalence of carbohydrate metabolism and lactic acid fermentation. The mRNA
      sequencing reads were mapped onto genomes of the six LAB strains, which showed
      that Lc. mesenteroides was most active during the early-stage fermentation,
      whereas gene expression by Lb. sakei and W. koreensis was high during later
      stages. However, gene expression by Lb. sakei decreased rapidly at 25 days of
      fermentation, which was possibly caused by bacteriophage infection of the
      Lactobacillus species. Many genes related to carbohydrate transport and
      hydrolysis and lactate fermentation were actively expressed, which indicated
      typical heterolactic acid fermentation. Mannitol dehydrogenase-encoding genes
      (mdh) were identified from all Leuconostoc species and especially Lc.
      mesenteroides, which harbored three copies (two copies on chromosome and one copy
      on plasmid) of mdh with different expression patterns. These results contribute
      to knowledge of the active populations and gene expression in the LAB community
      responsible for an important fermentation process.

PMID- 23558202
TI  - Cyclohexanone derivatives with cytotoxicity from the fungus Penicillium commune.
AB  - Four new cyclohexanone derivatives (2-5) and one known analog, (-)-Palitantin (1)
      were isolated from the EtOAc extract of Penicillium commune, a fungal strain of
      low-temperature habitats. The structures of 2-5 were determined on the basis of
      extensive spectroscopic analysis. Furthermore, the absolute configuration of 2
      was assigned by electronic circular dichroism (ECD) calculations, whereas that 3
      5 were deduced via the CD data. Cytotoxicities of 2-5 against five human
      carcinoma cell lines (Hela, A549, MCF7, HCT116, T24) were evaluated.

PMID- 23558203
TI  - Compound K, a final intestinal metabolite of ginsenosides, enhances insulin
      secretion in MIN6 pancreatic beta-cells by upregulation of GLUT2.
AB  - Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type
      ginsenosides from Panax ginseng and shows various bioactivities. Although it has
      also been found to have the property of anti-diabetes, the long-term effect of CK
      on insulin secretion in beta-cells is still unclear. In this study, CK was
      prepared from ginsenoside Rd by snailase hydrolysis and its effect on the insulin
      secretion activity in MIN6 pancreatic beta-cell lines in vitro was assessed. The
      expression of glucose transporter isoform-2 (GLUT2) and the cellular ATP content
      were also examined by western blot and HPLC analysis, respectively. The results
      showed that CK significantly enhanced insulin secretion, increased cellular ATP
      content, and upregulated the expression of GLUT2. These findings indicate that CK
      exerts prominent stimulatory effects on insulin secretion in the MIN6 cells
      partly via upregulating the expression of GLUT2.

PMID- 23558204
TI  - Saponins from Glycine max Merrill (soybean).
AB  - Saponins are a diverse group of plant secondary metabolites with a wide array of
      activities, as well as a significant role in nutrition and health. Saponins occur
      as multi-component mixtures of compounds with very similar polarities.
      Soysaponins are a special group of saponins. These represent the main source of
      saponins in Glycine max (soybeans, Fabaceae). In a study of the chemical
      profiling of plants, to investigate the possible misidentification and
      authentication of dietary supplements, the hydro-alcoholic extract of G. max was
      investigated. Three new saponins, designated as soysaponins M1 (1), M2 (2) and M3
      (3) along with seven known soysaponins (4-10) were isolated by normal and reverse
      phase liquid chromatography. All compounds were characterized by spectroscopic
      techniques including 2D NMR spectroscopy.

PMID- 23558205
TI  - A comparative study on poly(xylitol sebacate) and poly(glycerol sebacate):
      mechanical properties, biodegradation and cytocompatibility.
AB  - In order to develop degradable elastomers with a satisfactory combination of
      flexibility and enzyme-mediated degradation rate, the mechanical properties,
      enzymatic degradation kinetics and biocompatibility of poly(xylitol sebcate)
      (PXS) has been systematically investigated in comparison with poly(glycerol
      sebacate) (PGS). Under the same level of crosslinked density, the PXS elastomer
      networks have approximately twice the stretchability (elongation at break) of
      their PGS counterparts. This observation is attributable to the relatively longer
      and more orientable xylitol monomers, compared with glycerol molecules. Although
      xylitol monomers have two more hydroxyl groups, we, surprisingly, found that the
      hydrophilic side chains did not accelerate the water attack on the ester bonds of
      the PXS network, compared with their PGS counterpart. This observation was
      attributed to a steric hindrance effect, i.e. the large-sized hydroxyl groups can
      shield ester bonds from the attack of water molecules. In conclusion, the use of
      polyols of more than three -OH groups is an effective approach enhancing
      flexibility, whilst maintaining the degradation rate of polyester elastomers.
      Further development could be seen in the copolymerization of PPS with appropriate
      thermoplastic polyesters, such as poly(lactic acid) and polyhydroxyalkanoate.

PMID- 23558206
TI  - Degradation of tarsorrhaphy-related Vicryl sutures in the presence of orbital
      radiotherapy.

PMID- 23558207
TI  - Acute cilio-choroidal effusion due to acetazolamide: unusual posterior
      involvement (OCT aspects).

PMID- 23558208
TI  - Response to Yusuf and Watson.

PMID- 23558210
TI  - Tutoplast pericardium patch graft for scleral thinning following strabismus
      surgery.

PMID- 23558209
TI  - Disappearance of central confluent soft drusen following vitrectomy and ILM
      peeling.

PMID- 23558211
TI  - Intra-lesional interferon injection for recurrent conjunctival MALT lymphoma.

PMID- 23558212
TI  - Purtscher retinopathies: are we aiming at the wrong target?

PMID- 23558213
TI  - New insight into non-healing corneal ulcers: iatrogenic crystals.
AB  - AIMS: To characterise and correlate crystalline precipitations implicated in non
      healing corneal ulceration in two patients with a previous history of
      acanthamoeba keratitis. MATERIALS AND METHODS: Persistence of acanthamoeba and
      secondary bacterial infection was excluded with negative corneal scrapes.
      Confocal microscopy identified crystal-like deposits within the corneal stroma.
      To investigate possible precipitating combinations, all concurrent treatments at
      the time of presentation were mixed in wells, with observation of precipitate
      formation. Precipitates were observed with phase-contrast microscopy, and
      subsequently characterised via crystallography techniques and electrospray
      ionisation mass spectrometry. RESULTS: Combinations of dexamethasone 0.1% minims
      and chlorhexidine gluconate 0.2% formed an amorphous material characterised by
      electrospray ionisation mass spectrometry as an insoluble chlorhexidine salt.
      Combinations of chloramphenicol drops and timolol 0.5% formed a crystal
      identified via X-ray crystallography as santite (K(B5O6(OH)4).(H2O)2). This is a
      borate mineral identified in nature, arising from thermal springs, but never
      reported in biological tissues. Clinical improvement was observed following the
      cessation of the implicated precipitating combinations. CONCLUSION: Our
      observations suggest iatrogenic precipitate formation, with a potential
      deleterious effect upon healing. The substrates for these precipitates include
      several frequently prescribed topical ophthalmic treatments. These findings shed
      new light on the aetiopathogenesis of non-healing corneal ulceration, and have
      broad implications on topical prescribing for this challenging condition.

PMID- 23558214
TI  - Rapid response of retinal pigment epithelial detachments to intravitreal
      aflibercept in neovascular age-related macular degeneration refractory to
      bevacizumab and ranibizumab.
AB  - PURPOSE: The aim of this study is to report the short-term efficacy of
      aflibercept in the treatment of neovascular age-related macular degeneration
      (AMD) with associated retinal pigment epithelial detachment (PED) which is
      refractory or develops tachyphylaxis to bevacizumab and ranibizumab. METHODS: The
      method comprised a retrospective review of the medical records of patients with
      neovascular AMD and associated PEDs recently treated with aflibercept and
      previously treated with bevacizumab and ranibizumab. RESULTS: Three eyes of three
      female patients of ages 49, 55, and 65 years old with large serous PEDs and
      subretinal fluid (SRF) associated with occult choroidal neovascularization and
      neovascular AMD were treated with aflibercept after intravitreal bevacizumab
      and/or ranibizumab failed to resolve the lesions. All had complete resolution of
      SRF and complete or near-complete resolution of the PEDs after aflibercept
      injections over a 3-month period. Visual acuity improved in all three eyes.
      CONCLUSION: Intravitreal aflibercept may be an effective treatment option for
      serous PED in neovascular AMD patients after bevacizumab and ranibizumab have
      previously failed. Larger studies with longer follow-up are required to determine
      the role of aflibercept in treatment of PED in neovascular AMD.

PMID- 23558215
TI  - Long-term outcome of bilateral penetrating keratoplasty in a child with xeroderma
      pigmentosum: case report and literature review.

PMID- 23558216
TI  - An overview of natural variation studies in the Arabidopsis thaliana circadian
      clock.
AB  - Circadian clocks are ubiquitous mechanisms that provide an adaptive advantage by
      predicting subsequent environmental changes. In the model plant Arabidopsis
      thaliana (Arabidopsis), our understanding of the complex genetic network among
      clock components has considerably increased during these past years. Modeling has
      predicted the possibility of additional component to systematically and
      functionally complete the clock system. Mutagenesis screens have in the past been
      successfully employed to detect such novel components. With the advancement in
      sequencing technologies and improvements in statistical approaches, the extensive
      natural variation present in Arabidopsis accessions has emerged as a powerful
      alternative in functional gene discovery. In this review article, we review the
      previous efforts in mapping natural alleles affecting various clock parameters
      and will discuss further potentials of such natural-variation studies in
      physiological and ecological contexts. 

PMID- 23558217
TI  - Late gadolinium enhancement cardiac magnetic resonance imaging for the prediction
      of ventricular tachyarrhythmic events: a meta-analysis.
AB  - AIMS: Approaches to the risk stratification for sudden cardiac death (SCD) remain
      unsatisfactory. Although late gadolinium enhancement cardiac magnetic resonance
      imaging (LGE-CMR) for SCD risk stratification has been evaluated in several
      studies, small sample size has limited their clinical validity. We performed this
      meta-analysis to better gauge the predictive accuracy of LGE-CMR for SCD risk
      stratification. METHODS AND RESULTS: Electronic databases and published
      bibliographies were systematically searched to identify studies evaluating the
      association between the extent of LV scar on LGE-CMR and ventricular arrhythmic
      events [SCD, resuscitated cardiac arrest, the occurrence of ventricular
      arrhythmias, or appropriate implantable cardioverter defibrillator (ICD)
      therapy]. Only studies enrolling patients with CAD or non-ischaemic
      cardiomyopathy were included. Summary estimates of the relative risk (RR) and
      likelihood ratios (LRs) were calculated using random effects models. Eleven
      studies comprising 1105 patients were identified. During a mean/median follow-up
      of 8.5-41 months 207 patients had ventricular arrhythmic events. Ventricular
      arrhythmic events were more common in patients with a greater extent of LV scar:
      RR 4.33 [95% confidence interval (CI) 2.98-6.29], positive LR 1.98 (95% CI 1.66
      2.37), and negative LR 0.33 (95% CI 0.24-0.46). CONCLUSION: The extent of LGE on
      CMR is strongly associated with the occurrence of ventricular arrhythmias in
      patients with reduced LVEF and may be a valuable risk stratification tool for
      identifying patients who will benefit from ICD therapy. However, uncertainties
      regarding clinical application persist and need to be addressed prior to
      introduction into broad clinical practice.

PMID- 23558218
TI  - Erythropoietin and heart failure: the end of a promise?

PMID- 23558219
TI  - Maximal cardiorespiratory fitness testing in individuals with chronic stroke with
      cognitive impairment: practice test effects and test-retest reliability.
AB  - OBJECTIVES: To evaluate, for individuals with chronic stroke with cognitive
      impairment, (1) the effects of a practice test on peak cardiorespiratory fitness
      test results; (2) cardiorespiratory fitness test-retest reliability; and (3) the
      relationship between individual practice test effects and cognitive impairment.
      DESIGN: Cross-sectional. SETTING: Rehabilitation center. PARTICIPANTS: A
      convenience sample of 21 persons (men [n=12] and women [n=9]; age range, 48-81y;
      44.9+/-36.2mo poststroke) with cognitive impairments who had sufficient lower
      limb function to perform the test. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Peak oxygen consumption (Vo(2)peak, ml.kg(-1).min(-1)). RESULTS: Test
      retest reliability of Vo(2)peak was excellent (intraclass correlation coefficient
      model 2,1 [ICC2,1]=.94; 95% confidence interval [CI], .86-.98). A paired t test
      showed that there was no significant difference for the group for Vo(2)peak
      obtained from 2 symptom-limited cardiorespiratory fitness tests performed 1 week
      apart on a semirecumbent cycle ergometer (test 2-test 1 difference, -.32ml.kg(
      1).min(-1); 95% CI, -.69 to 1.33ml.kg(-1).min(-1); P=.512). Individual test
      retest differences in Vo(2)peak were, however, positively related to general
      cognitive function as measured by the Mini-Mental State Examination (rho=.485;
      P<.026). CONCLUSIONS: Vo(2)peak can be reliably measured in this group without a
      practice test. General cognitive function, however, may influence the effect of a
      practice test in that those with lower general cognitive function appear to
      respond differently to a practice test than those with higher cognitive function.

PMID- 23558220
TI  - Decreased tissue levels of cyclophilin A, a cyclosporine a target and phospho
      ERK1/2 in simvastatin patients with abdominal aortic aneurysm.
AB  - BACKGROUND: Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences
      abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in
      animal and in vitro studies. Statins decrease CyPA in smooth muscle cells
      although their influence on CyPA in human AAA is unknown. MATERIAL AND METHODS:
      The study was performed on AAA wall-tissue samples obtained from 30 simvastatin
      treated and 15 non-statin patients (2:1 case to control). The patients were
      matched by age, sex and AAA diameter. We investigated the gene expression of
      CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by
      real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular
      signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. RESULTS:
      The AAA wall tissue from simvastatin-treated patients had significantly lower
      CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively).
      Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the
      simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin
      did not influence EMMPRIN gene and protein expression. CONCLUSION: Simvastatin
      treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA
      intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the
      interference with signalling pathways leading to CyPA formation and ERK1/2
      activation reveals a new anti-inflammatory role of statins in AAA.

PMID- 23558221
TI  - The importance of interleaflet triangles for aortic valve competence in a marfan
      patient with dilated aortic sinuses.
AB  - We report a case of advanced aortic sinus aneurysm without the aggravation of
      aortic valve regurgitation after a simple reduction procedure for dilated aortic
      root base and sinotubular junction (STJ) in a Marfan patient with annuloaortic
      ectasia and severe aortic valve regurgitation. The aortic valve competence was
      well preserved by limited change of distances among the interleaflet triangles
      after reduction of the dilated aortic root base and STJ in the Marfan patient,
      although the sinus dilatation was aggravated. 

PMID- 23558222
TI  - Intrathoracic displacement of a fractured humeral head due to blunt trauma.
AB  - The incidence of a fractured humeral head penetrating into the thoracic cavity is
      extremely rare. A 46-year-old woman presented with moderate respiratory distress
      at the emergency department after being involved in a motor vehicle accident.
      Radiographic examinations revealed fractures of the second to fifth ribs on the
      left side along with hemopneumothorax and fracture-dislocation of the humeral
      head into the thoracic cavity. After initial stabilization, video-assisted
      thoracic surgery (VATS) was performed to remove the fractured humeral head, and
      this was followed by a hemiarthroplasty. In this case report, we have discussed
      significant aspects of this uncommon finding in order to alert surgeons of the
      potential risks associated with intrathoracic displacement of the fractured
      humeral bone in trauma patients. 

PMID- 23558223
TI  - Mitral valve plasty for idiopathic rupture of mitral valve posterior chordae in
      infants.
AB  - INTRODUCTION: Idiopathic mitral valve chordal rupture is rare among infants. Once
      it has occurred, acute heart failure progresses, and emergency surgical repair is
      necessary in most cases. Our surgical experience with idiopathic mitral valve
      chordal rupture is reported. PATIENTS AND METHODS: From September 2008 to May
      2012, four infants (3 males, 1 female; median age 5.5 months) underwent mitral
      valve plasty for severe mitral valve regurgitation due to prolapse of posterior
      mitral valve leaflet. Patient history, surgical procedure, operation time,
      mortality, postoperative echocardiography data (mitral valve regurgitation grade:
      0-trivial, mild, moderate, severe, transmitral flow: TMF) and pathology were
      examined. RESULTS: Three cases required emergency surgery; 1 case, elective
      surgery. Intraoperative findings showed chordal rupture of the P2 segment in 3
      cases and P1 + P3 segments in 1 case. Quadrangular resection with annular
      plication was performed for 1 case. Quadrangular resection with annular plication
      and the Kay procedure were performed for 3 cases. Mitral valve regurgitation
      improved from severe to trivial-mild in all cases. Pathological examination
      showed a myxomatous degenerative change in the mitral valve. CONCLUSION: Mitral
      valve plasty was performed for idiopathic mitral valve chordal rupture in
      infants. The surgical procedures were the same as for adult cases and achieved
      satisfactory results.

PMID- 23558224
TI  - Impact of medical treatment on long-term results after surgical ablation of
      atrial fibrillation in cardiac surgical patients.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term outcome (4 years)
      of high-intensity-focused-ultrasound (HIFU) cardiac ablation, the significance of
      postablation antiarrhythmic drugs (AADs) and predictors of successful sinus
      rhythm (SR) restoration. METHODS: 103 patients were prospectively enrolled in a
      single-center study. The preoperative atrial fibrillation (AF) type was
      paroxysmal in 36%, permanent in 53%, persistent in 5% and flutter in 6% patients.
      The left atrial diameter was <50 mm in 78 patients and >50 mm in 25. Long-term
      results, up to 4 years, and postablation antiarrhythmics were evaluated. Follow
      up studies including 12-lead electrocardiogram (ECG) and 24-h Holter ECG obtained
      at 3 and 6 months in our institute, and 12, 24, and 48 months during outpatient
      visits. RESULTS: No device- or procedure-related complications or deaths were
      observed. A pacemaker was implanted in 5% patients. Freedom from AF and flutter
      at 6-/12-/and 48-month visit were 66%/63%/68% for the entire population,
      84%/77%/90% in patients with paroxysmal AF, 50%/46%/40% in patients with
      permanent AF and at any time in all 6 patients with flutter. No significant
      changes were noted at 2 years.Postablation results were not statistically
      different in patients on or not on antiarrhythmic therapy. At discharge, 53% of
      patients on antiarrhythmics and 55%, not on AADs were free of AF. At the 6-month
      visit, 66% of patients on AADs versus 69% of patients, not on AADs presented with
      SR, an improved outcome by 13 percentage points with AADs versus 14 percentage
      points without AADs (p = 0.65). Patients taking a beta-blocker showed better
      results in restoration/maintenance of SR after 6 months. No significant
      difference was noted regarding the use of UltraWand.Sixty-seven percent with a
      left atrium (LA) diameter <50 mm were successfully converted into SR, vs. 48%
      with an LA diameter >50 mm. Best results were achieved in patients with
      paroxysmal AF and LA <50 mm with 81% freedom of AF. CONCLUSION: AF treatment with
      HIFU ablation during concomitant cardiac surgery is a safe and effective
      procedure for restoring SR, especially in patients with AF and especially in
      patients with a smaller left atrial diameter. No significant difference was noted
      between the antiarrhythmic and non drug groups regarding restoration and
      maintaining SR; however, better results were achieved by those taking a beta
      blocker.

PMID- 23558225
TI  - Lung squamous cell carcinoma in a young female never smoker: a case report.
AB  - A lung squamous cell carcinoma complicated by lung abscess was found in a 38-year
      old female never smoker. After a transbronchial lung biopsy, she complained of
      chest pain and had a persistent fever. A right middle lobectomy was performed to
      alleviate her symptoms and complete surgical resection was achieved. She reported
      no exposure to factors that increase the likelihood of lung cancer. Unknown
      factors or the patient's lung cancer susceptibility might cause the disease.
      Survival time is generally shorter in young patients than old patients, but
      careful observation and aggressive treatment can improve prognoses. A case such
      as this is rare in the extant literature. 

PMID- 23558226
TI  - A case of desmoid-type fibromatosis arising after thoracotomy for lung cancer
      with a review of the english and Japanese literature.
AB  - Chest wall desmoid-type fibromatoses are rare, locally aggressive tumors that
      occasionally arise from previous thoracotomy sites. Tumors arising from previous
      sites of thoracotomy to treat malignant disease should be discriminated from the
      pleural dissemination of the previous malignancy. In this study, we report a case
      of desmoid-type fibromatosis arising from a site for thoracotomy to treat lung
      cancer. Additionally we reviewed 15 reported cases of desmoid-type fibromatosis
      following thoracotomy and summarized their features. A 62-year-old woman was
      found to have a tumor on computed tomography (CT) at a 1-year routine checkup for
      lung cancer. The tumor (diameter, 3.4 cm) was located at the previous thoracotomy
      site. Positron emission tomography (PET) revealed mild (18)F-fluorodeoxyglucose
      (FDG) accumulation in the tumor, with a maximal standardized uptake value
      (SUVmax) of 1.9. CT-guided biopsy revealed only fibrous tissue. Eighteen months
      after the biopsy, CT revealed apparent tumor growth, and a biopsy revealed the
      same histology observed previously. The tumor was removed and diagnosed as
      desmoid-type fibromatosis. Currently, the patient is alive without recurrence 4
      years after desmoid surgery. 

PMID- 23558227
TI  - A case of Castleman's disease with myasthenia gravis.
AB  - A rare case of Castleman's disease with myasthenia gravis is reported. A 55-year
      old woman with bilateral ptosis, speech impairment, and severe dyspnea had been
      previously diagnosed with myasthenia gravis. Computed tomography showed a 5 cm *
      3 cm paratracheal mass in the mediastinum, thought to be an ectopic thymoma. Two
      days after surgical resection, the patient suddenly developed dyspnea.
      Postoperative myasthenic crisis was diagnosed, and plasmapheresis was performed.
      Her general condition improved, and her subsequent course was uneventful. The
      final pathological diagnosis was mediastinal solitary Castleman's disease,
      hyaline vascular type. Castleman's disease with myasthenia gravis is especially
      rare. One of the serious complications is postoperative myasthenic crisis. For
      patients with myasthenia gravis, the rate of postoperative myasthenic crisis
      seems significantly higher in Castleman's disease patients than in patients with
      thymic epithelial tumors. Castleman's disease with myasthenia gravis is discussed
      along with a review of the literature. 

PMID- 23558228
TI  - Comparison of the health related quality of life of patients following mitral
      valve surgical procedures in the 6-months follow-up: a prospective study.
AB  - PURPOSE: The aim of the present study is to evaluate the health-related quality
      of life of the patients who underwent mitral valve repair (MvRp) and mitral valve
      replacement (MVR). METHODS: Within the scope of this prospective study design, 56
      patients who had mitral valve operation between the years of 2011-2012 were
      enrolled in the study. 24 (42.8%) of these patients had MVR while 32 (57.1%) of
      them had MvRp. The health-related quality of life was evaluated according to the
      Turkey norms of Short Form 36 Quality-Of-Life Measures (SF-36), which were filled
      in by the patients before and 6 months after the operation. Moreover,
      preoperative risk factors affecting the quality of life (age, gender, functional
      capacity, rhythm, hypertension, diabetes, applied surgical method and
      echocardiographic results) were investigated for all the patients (n = 56) by
      using independent sample t test analysis. RESULTS: When the pre and postoperative
      changes were compared between the two groups, it was found out that there were no
      significant difference between the groups in terms of restraints on physical role
      functioning (PR), and the social role functioning values (SF) (respectively; p =
      0.097, p = 0.105). However, in the comparison of pre-/postoperative changes
      between the groups, the changes in physical functioning (PF), bodily pain (BP),
      general health (GH), vitality (VT) and restraints on emotional role functioning
      (RE) and mental health (MH) values were found out to be significantly superior in
      the MvRp group than in the MVR group (respectively; p <0.01, p <0.05, p <0.01, p
      <0.01, p <0.05 and p <0.01). It was also confirmed that female gender, atrial
      fibrillation (AFR), and MVR method negatively affected the physical and mental
      components (respectively; p = 0.033, p = 0.003, p = 0.015). CONCLUSION: RESULTS
      of the SF-36 quality of life measures show that quality of life may be better in
      patients that have had MvRp. It should be considered that the planned surgical
      treatment method can affect the patient's quality of life, and this effect can
      indicate the success of the surgical treatment.

PMID- 23558229
TI  - Management of infective endocarditis with cerebral complications.
AB  - PURPOSE: Management of patients with infective endocarditis complicated by
      neurological deficits is challenging. No clear management guidelines have been
      defined, and the timing of surgery remains controversial. The purpose of this
      study was to evaluate our management algorithm. METHODS: Thirty-eight adult
      patients with left-sided infective endocarditis undergoing valve surgery were
      analyzed. Before the operation, enhanced brain computed tomography (CT) was
      performed to rule out a cerebral complication. Pre and postoperative data were
      retrospectively reviewed to clarify whether our algorithm was effective. Sixteen
      patients having neurological complication (CVC group) were compared with 22
      patients without neurological complication. RESULTS: Age, sex, New York Heart
      Association (NYHA) functional class, affected valve and pathogens were not
      different between two groups. Mean interval from the onset of neurological
      dysfunction to cardiac operation was 27.8 +/- 27.8 days (median 23 days). Of the
      16 CVC group patients, 12 experienced cerebral infarction. Mass effects were seen
      in 3 patients, with 1 of these 3 patients died following aneurysm rupture.
      Mycotic aneurysm was detected in 4 patients, with 3 undergoing successful staged
      operations. Mortality and postoperative neurological exacerbation in CVC group
      was 6.3% (1 patient). Most patients who fulfilled the algorithm showed good
      outcomes. CONCLUSIONS: Our suggested management algorithm for infective
      endocarditis appears effective.

PMID- 23558231
TI  - Involvement of dietary salt in shaping bacterial communities in European sea bass
      (Dicentrarchus labrax).
AB  - Bacteria associated with the digestive tract of multicellular organisms have been
      shown to play a major role in their hosts' functioning. In fish, it has been
      proposed that food fermentation occurs inside the pyloric ceca, pouch like organs
      found in their digestive tract. However, this notion remains controversial.
      Furthermore, changes in pyloric cecal bacterial populations under different diets
      have yet to be demonstrated in fish. In this study, we explore the changes
      occurring in the bacterial community residing in the pyloric ceca of carnivorous
      fish fed different diets, which were shown to induce different growth rates. Our
      results revealed that different diets do indeed induce distinct bacterial
      compositions within the pyloric ceca. We found that, when salt was added to a low
      fish meal diet, the bacterial changes were accompanied by a significant
      enhancement in weight gain, hinting at a possible involvement of the bacterial
      community in energy harvest.

PMID- 23558232
TI  - Trichostatin A protects against cisplatin-induced ototoxicity by regulating
      expression of genes related to apoptosis and synaptic function.
AB  - OBJECTIVE: Although inhibition of histone deacetylases (HDACs) has been shown to
      protect against cisplatin-induced hearing loss, the underlying mechanism is still
      poorly understood. In the present study, we aim to investigate the protective
      effect of trichostatin A (TSA), a specific inhibitor of HDACs, on cisplatin
      induced ototoxicity and to determine the differentially expressed genes involved
      in this process. METHODS: The basilar membrane of the cochlea was isolated from 3
      day newborn Wistar rats. Organotypic cultures were treated with 150 MUM cisplatin
      or 200 nM TSA. For combination treatment, cells were pre-incubated with TSA for
      1h, followed by TSA plus cisplatin treatment. Rhodamine-phalloidin staining was
      used to label hair cells, and immunocytochemistry with an anti-neurofilament-200
      antibody was applied to label spiral ganglion neurons (SGNs). Global expression
      profile microarray analysis was used to identify differentially expressed genes.
      Molecular function and signal pathway analysis were performed using a protein
      analysis through evolutionary relationships (PANTHER) classification system. Real
      time quantitative PCR (qPCR) was carried out for data validation. RESULTS: Severe
      loss of hair cells and SGNs occurred after 48 h of cisplatin incubation, while
      TSA significantly increased the number of hair cells and SGNs in the combination
      treatment group (P<0.05). Compared with control, expression of 71 genes were up
      regulated and 383 genes were down-regulated upon cisplatin treatment. Addition of
      TSA induced the up-regulation of 1387 genes and down-regulation of 1226 genes as
      compared with cisplatin administration alone. After cisplatin treatment, we
      observed significant down-regulation of mRNA for several genes related to
      synaptic function genes, including Camk2a, Camk2b, Vglut1, Snap25 and Rab3b,
      whereas pretreatment with TSA elevated mRNA levels of these genes. TSA greatly
      decreased expression of genes related to the calcium signaling pathway (Capn1 and
      Capn2) and apoptosis signaling pathway (Tnfrsf1a and Tp53), while addition of TSA
      significantly reduced levels of Tnfrsf1a and Tp53 compared with cisplatin alone
      (P<0.01). CONCLUSIONS: Our results suggested that TSA might protect against
      cisplatin-induced ototoxicity via mediating expression of genes responsible for
      regulating apoptosis, intracellular calcium homeostasis, neurotransmitter
      synthesis and release, and synaptic plasticity.

PMID- 23558234
TI  - Hepatic oxidative stress in Mongolian gerbils experimentally infected with
      Babesia divergens.
AB  - The present study aimed to investigate oxidative stress, DNA damage, and
      histopathological alterations in hepatic tissues of Mongolian gerbils
      experimentally infected with Babesia divergens. It was found that parasitaemia
      reached approximately 77% at day 5 post-infection. The liver became dark-brown
      and extremely friable, and hepatic sinusoids were dilated and contained
      macrophages and parasite-containing erythrocytes. Infection also induced
      inflammation and injury of the liver. This was illustrated by (1) an increase in
      inflammatory cellular infiltrations, (2) a decrease in total antioxidant
      capacity, as indicated by lowered glutathione and catalase levels, (3) increased
      production of nitric oxide-derived products (nitrite/nitrate) and
      malondialdehyde, and (4) increased lactic acid dehydrogenase activity and protein
      carbonyl content in the liver. Infection also interfered with the normal cell
      cycle of the hepatic tissue, as indicated by a significant increase in the
      percentage of liver cells at G0/G1 from approximately 86.2% to 97.5% and in S
      phases from 0.28% to 2.2%. Collectively, the present data suggest that B.
      divergens infection could induce cell-cycle alteration following oxidative stress
      and DNA damage in hepatic tissue. Further work is required to investigate the
      mechanism by which this hepatic tissue damage takes place.

PMID- 23558233
TI  - Systems analysis of genetic variation in MPTP neurotoxicity in mice.
AB  - We analyzed genetic variation in severity of neuronal damage using the known
      dopaminergic neurotoxicant, MPTP, as a prototypical chemical denervation agent.
      Male mice from ten members of the BXD family of recombinant inbred strains
      received 12.5 mg/kg MPTP s.c. (vs. saline) and 48 h later brains were taken for
      multiple related biochemical analyses. Striatal dopamine (DA) and its
      metabolites, DOPAC and HVA, and serotonin and its metabolite, 5-HIAAA, were
      analyzed by HPLC. DA turnover was assessed using DOPAC/DA and HVA/DA ratios.
      Striatal tyrosine hydroxylase (TH), glial fibrilary acidic protein (GFAP), and
      iron content in ventral midbrain were quantified. All dopamine measures, as well
      as TH and GFAP, demonstrated wide, genotype-dependent differences in response to
      MPTP. Serotonin was largely unaffected. Principal components analysis (PC) on
      difference values, saline minus MPTP, for DA, DOPAC, HVA, and TH, yielded a
      dominant principal component. The PC trait residuals for each genotype were
      compared against complementary expression data for striatum of the same strains.
      Three transcripts representing Mtap2, Lancl 1, and Kansl1l were highly correlated
      with the PC, as was the difference score, MPTP minus saline for GFAP. This
      systems approach to the study of environmental neurotoxicants holds promise to
      define individual genetic differences that contribute to variability in
      susceptibility to risk factors for diseases such as Parkinson's disease.

PMID- 23558235
TI  - Independent effects of 5' and 3' functional variants in the serotonin transporter
      gene on suicidal behavior in the context of childhood trauma.
AB  - The serotonin transporter, encoded by the SLC6A4 gene, influences the synaptic
      actions of serotonin and is responsive to stress hormones. We hypothesized that 5
      HTTLPR, a functional SLC6A4 promoter polymorphism, and two tightly-linked,
      putatively functional 3' UTR SNPs (rs3813034, rs1042173) might have independent
      effects on suicidal behavior in the context of childhood trauma (CT). DNA and
      Childhood Trauma Questionnaire scores were available for a total of 474 African
      Americans, including 112 suicide attempters and 362 non-suicide attempters.
      Genotyping was performed for the triallelic 5-HTTLPR polymorphism, 14 SLC6A4
      haplotype-tagging SNPs, and 186 ancestry informative markers. There were
      independent G * E interactive effects of 5-HTTLPR (p = 0.017) and the rs3813034
      rs1042173 diplotype (p = 0.011) on suicidal behavior. In individuals exposed to
      high CT the risk of suicide attempt was 0.52 in carriers of the low activity 5
      HTTLPR variant and 0.32 in medium/high activity variant carriers. Likewise, CT
      exposed carriers of the major rs3813034-rs1042173 ATAT diplotype had an increased
      risk of suicidal behavior relative to the ATCG/CGCG diplotype carriers (0.40 vs
      0.31). Neither the 5' nor the 3' functional variants had an effect in individuals
      without CT: suicide attempt risk = 0.12-0.22. In individuals exposed to high CT
      the prevalence of suicide attempt was 0.56 in carriers of both 5' and 3' risk
      variants, 0.39 in carriers of one risk variant and 0.25 in individuals without
      either risk variant. Our findings suggest that the 5' and 3'SLC6A4 functional
      variants have independent effects on the risk for suicidal behavior in CT exposed
      individuals.

PMID- 23558236
TI  - Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid
      derivatives.
AB  - In the present investigation, 16 new rotundic acid (RA) derivatives modified at
      the C-3, C-23 and C-28 positions were synthesized. The cytotoxicities of the
      derivatives were evaluated against HeLa, A375, HepG2, SPC-A1 and NCI-H446 human
      tumor cell lines by MTT assay. Among these derivatives, compounds 4-7 exhibited
      stronger cell growth inhibitory than RA and compound 4 was found to be the best
      inhibition activity on five human tumor cell lines with IC50 <10 MUM. The
      apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot
      analysis. The results indicated that compound 4 could induce apoptosis through
      increasing protein expression of cleaved caspase-3 and Bax, and decreasing
      protein expression of Bcl-2. In summary, the present work suggests that compound
      4 might serve as an effective chemotherapeutic candidate.

PMID- 23558237
TI  - A novel series of histamine H4 receptor antagonists based on the pyrido[3,2
      d]pyrimidine scaffold: comparison of hERG binding and target residence time with
      PF-3893787.
AB  - In this work we describe the optimization of a lead compound based on the
      quinazoline template to give a new series of potent pyrido[3,2-d]pyrimidines as
      histamine H4 receptor antagonists. The pyrido[3,2-d]pyrimidine ligands have
      significantly reduced hERG binding compared to clinical stage compound PF-3893787
      while showing good affinities at the human and rodent histamine receptors. The
      receptor residence time of several of these new compounds was determined for the
      human H4R and compared with JNJ7777120 and PF-3893787. The pyrido[3,2
      d]pyrimidines showed residence times lower than JNJ7777120 but comparable to the
      residence time of PF-3893787. Overall, the pyrido[3,2-d]pyrimidines show an
      excellent in vitro profile that warrants their further investigation in relevant
      models of human disease.

PMID- 23558239
TI  - Management for pancreatolithiasis: a Japanese multicenter study.
AB  - OBJECTIVES: A Japanese multicenter study of pancreatolithiasis was performed to
      investigate its clinical features and determine treatment strategies for
      pancreatolithiasis. METHODS: A retrospective study was performed on 916 patients
      managed in 34 institutions for a period of more than 5 years. RESULTS: The
      treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479
      patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones
      after ESWL was achieved in 92.4% of the patients. However, complete stone
      clearance was achieved in 49.4% of the patients after ESWL alone. The complete
      stone clearance rate was lower after ESWL than after endoscopy (87.9%). The
      incidence of early complications was significantly higher after surgery (13.3%)
      than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL
      (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery
      (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently
      than after surgery (2.2%). Stones and abdominal pain most often recurred within 3
      years after ESWL and endoscopy. CONCLUSIONS: First-line treatment of pancreatic
      stones should be ESWL alone or with endoscopy because of its minimal invasiveness
      and low incidence of early complications. Surgery should be performed on patients
      in whom ESWL and endoscopy failed.

PMID- 23558238
TI  - Daphnane-type diterpenes with inhibitory activities against human cancer cell
      lines from Daphne genkwa.
AB  - Four new daphnane-type diterpenes, genkwadanes A-D (1-4), together with 19 known
      ones, were isolated from ethanol extract of the flower buds of Daphne genkwa.
      Their structures were determined on the basis of extensive spectroscopic data.
      Among them, daphnane-type diterpene with a 1,10-double bond (1) was isolated from
      this plant for the first time. The cytotoxicity of all compounds 1-23 against the
      10 selected human cancer cell lines was assayed. A number of compounds exhibited
      significant activities against the 10 cancer cell lines (IC50<9.56 MUM). and most
      interestingly, all the compounds revealed preferred cytotoxicities on the HT-1080
      cell line and displayed much stronger inhibitory activities (IC50<29.94 MUM)
      compared with positive control 5-fluorouracil (IC50=35.62 MUM), particularly,
      compounds 9-11, 13, 16 and 19 exhibited the strongest cytotoxicity activities
      against the HT-1080 cell line (IC50<0.1 MUM).

PMID- 23558240
TI  - Antioxidant status and oxidative stress markers in pancreatic cancer and chronic
      pancreatitis.
AB  - OBJECTIVES: Oxidative stress has been implicated in the pathogenesis of chronic
      pancreatitis (CP) and pancreatic cancer (PC). The study aim was to assess the
      oxidative stress markers and antioxidant defense system in patients with CP and
      those with PC. METHODS: Activities of superoxide dismutase 1 (SOD1), catalase
      (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), arylesterase
      (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and
      concentrations of reduced glutathione, conjugated dienes in low-density
      lipoprotein (CD/LDL) and oxidized LDL (ox-LDL/LDL) were assessed in 50 PC and 50
      CP patients and 50 age and sex-matched controls. RESULTS: Comparison of PC and CP
      groups to controls found the following changes: glutathione peroxidase 1 (GPX1) (
      20.2%, -25.5%; P < 0.001), glutathione reductase (GR) (-9.5%, -11.9%; P < 0.05),
      SOD1 (+22.9%; P < 0.01), CAT (-10.6%; P < 0.05), PON1-A (-34.3%, -16.0%; P <
      0.001), PON1-L (-44.2%; -17.0%; P < 0.01), conjugated dienes in LDL (CD/LDL)
      (+20%, +33.3%; P < 0.05) and ox-LDL/LDL (+42.2%, +14.4%; P < 0.05). The patients
      with PC had changed activities and levels of SOD1 (+24.2%), CAT (-10.4); P <
      0.01), PON1-A (-21.7%), PON1-L (-32.9%), and ox-LDL/LDL (+24.3%); (all P < 0.01)
      compared with the patients with CP. CONCLUSIONS: Reduced antioxidant defense
      system capacity and increased markers of oxidative stress were found in PC and
      CP. PON1-L and CAT activities, along with ox-LDL/LDL levels, were the independent
      factors differentiating the patients with PC from the patients with CP.

PMID- 23558241
TI  - Should we do EUS/FNA on patients with pancreatic cysts? The incremental
      diagnostic yield of EUS over CT/MRI for prediction of cystic neoplasms.
AB  - OBJECTIVES: To evaluate the performance characteristics of endoscopic
      ultrasonography (EUS) compared with computed tomography (CT) and magnetic
      resonance imaging (MRI) and determine the incremental diagnostic yield and
      accuracy of EUS with or without fine needle aspiration (FNA) over CT and MRI for
      prediction of neoplastic pancreatic cysts. METHODS: The EUS database was queried
      for procedures performed for pancreatic cysts between March 2006 and January
      2010. Cystic pancreatic ductal adenocarcinoma, cystic pancreatic neuroendocrine
      tumor, mucinous cystic neoplasm, intraductal papillary neoplasm, and solid
      pseudopapillary neoplasm were categorized as neoplastic; pseudocysts and serous
      cysts were designated as nonneoplastic/low risk. RESULTS: Final diagnoses were
      established by surgery in 154 patients (mucinous cystic neoplasm/intraductal
      papillary neoplasm [69.4%], pancreatic neuroendocrine tumor [10%], pancreatic
      ductal adenocarcinoma [6.4%], solid pseudopapillary neoplasm [0.6%],
      nonneoplastic/low risk [13.6%]). Endoscopic ultrasonography with or without FNA
      was superior to CT and MRI in accurately classifying a cyst as neoplastic (P <
      0.0001). After CT and MRI, EUS increased the rate of correctly predicting
      neoplastic cysts in 43 (36%) and 27 (54%) additional cases, respectively.
      CONCLUSIONS: The incremental increase in diagnostic yield of EUS and fluid
      analysis over CT and MRI for prediction of a neoplastic cyst is 36% and 54%,
      respectively. The addition of EUS-FNA to abdominal imaging significantly
      increases overall accuracy for diagnosis of neoplastic pancreatic cysts.

PMID- 23558242
TI  - Solid organ transplant patients experience high rates of infection and other
      complications after total knee arthroplasty.
AB  - Survival after solid organ transplants in the United States is increasing, and
      there is a need to understand the complications in knee arthroplasty patients who
      underwent organ transplantation. A retrospective study was conducted from 1993
      2008 on 19 patients (23 knee arthroplasties) with previous successful solid organ
      transplants. Eleven knee arthroplasties were performed after renal
      transplantation, and 12 after nonrenal solid organ transplant (seven liver, four
      heart, one lung). Complications occurred in 9/23 patients (39.1%) and infections
      occurred in 4/23 patients (17.3%). Of the infected knees, two had MRSA, one had
      MSSA, and one Escherichia coli. Noninfectious complications (5/24, 21.7%) include
      aseptic loosening, quadriceps rupture, femoral fracture, hemarthrosis, and
      arthrofibrosis. All patients with complications were on immunosuppressant
      medications at the time of arthroplasty. There was a significantly higher rate of
      infection in the renal group compared to the non-renal group (P = 0.022). There
      was also a higher overall complication rate in the renal group however this did
      not reach significance.

PMID- 23558244
TI  - Breast ultrasound in 22,131 asymptomatic women with negative mammography.
AB  - PURPOSE: To evaluate increment cancer detection rate generated by ultrasound
      (US). MATERIALS AND METHODS: US only detected cancers were assessed for 22,131
      self-referring asymptomatic women with negative mammography and subgroups by age,
      previous cancer, breast density. Invasive assessment and surgical biopsy rate
      were evaluated. RESULTS: The overall US detection was 1.85 per thousand
      (41/22,131). In the subgroups it was: 1.95 per thousand (22/11,274) in women <50
      years vs 1.75 per thousand (19/10,857) in women >= 50 years (p = 0.42), 5.49 per
      thousand (12/2183) in women with previous cancer vs 1.45 per thousand (29/19,948)
      in women without cancer history (p = 0.0004), 2.21 per thousand (22/9960) in
      dense breasts (p = 0.17) vs 1.56 per thousand (19/12,171) in fatty breasts. The
      US generated invasive assessment was 1.9% (422/22,131). The benign to malignant
      open surgical biopsy ratio was 0.17 (7/41). CONCLUSION: Adding US to negative
      mammography allowed for substantial incremental cancer detection rate (1.85 per
      thousand), particularly at age <50 years, in women with previous breast cancer
      and in dense breasts.

PMID- 23558245
TI  - Predicting dengue outbreaks using approximate entropy algorithm and pattern
      recognition.
AB  - OBJECTIVES: The prediction of dengue outbreaks is a critical concern in many
      countries. However, the setup of an ideal prediction system requires establishing
      numerous monitoring stations and performing data analysis, which are costly, time
      consuming, and may not achieve the desired results. In this study, we developed a
      novel method for predicting impending dengue fever outbreaks several weeks prior
      to their occurrence. METHODS: By reversing moving approximate entropy algorithm
      and pattern recognition on time series compiled from the weekly case registry of
      the Center for Disease Control, Taiwan, 1998-2010, we compared the efficiencies
      of two patterns for predicting the outbreaks of dengue fever. RESULTS: The
      sensitivity of this method is 0.68, and the specificity is 0.54 using Pattern A
      to make predictions. Pattern B had a sensitivity of 0.90 and a specificity of
      0.46. Patterns A and B make predictions 3.1 +/- 2.2 weeks and 2.9 +/- 2.4 weeks
      before outbreaks, respectively. CONCLUSIONS: Combined with pattern recognition,
      reversed moving approximate entropy algorithm on the time series built from
      weekly case registry is a promising tool for predicting the outbreaks of dengue
      fever.

PMID- 23558243
TI  - Multi-heme proteins: nature's electronic multi-purpose tool.
AB  - While iron is often a limiting nutrient to Biology, when the element is found in
      the form of heme cofactors (iron protoporphyrin IX), living systems have excelled
      at modifying and tailoring the chemistry of the metal. In the context of proteins
      and enzymes, heme cofactors are increasingly found in stoichiometries greater
      than one, where a single protein macromolecule contains more than one heme unit.
      When paired or coupled together, these protein associated heme groups perform a
      wide variety of tasks, such as redox communication, long range electron transfer
      and storage of reducing/oxidizing equivalents. Here, we review recent advances in
      the field of multi-heme proteins, focusing on emergent properties of these
      complex redox proteins, and strategies found in Nature where such proteins appear
      to be modular and essential components of larger biochemical pathways. This
      article is part of a Special Issue entitled: Metals in Bioenergetics and
      Biomimetics Systems. 

PMID- 23558246
TI  - Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous
      diabetes and hepatocellular carcinoma in cirrhotic patients.
AB  - BACKGROUND: Hepatogenous diabetes (HD) occurs as a complication of cirrhosis.
      Whether genetic factors, rather than only liver damage, play roles in the
      development of HD is unknown. TCF7L2 gene has been reported to be associated with
      type 2 diabetes and also cancer risks. We aim to evaluate the impact of TCF7L2
      gene on the susceptibility of HD and hepatocellular carcinoma (HCC) in a Chinese
      Han population. PATIENTS AND METHODS: A total of 367 adult liver transplant
      candidates with liver cirrhosis were included. Fifteen tag single nucleotide
      polymorphisms (SNPs) were selected from HapMap CHB database with a minor allele
      frequency of >0.2 and r(2) of >0.8. Another three SNPs were also chosen because
      of their close association with type 2 diabetes in East Asian. RESULTS: Patients
      with HD presented significantly poorer liver function, higher incidence of
      cirrhotic complications and higher insulin resistance compared with non-HD
      patients. Three SNPs were differentially distributed between HD patients and non
      HD patients. In multivariate logistic analysis, TCF7L2 rs290487 and rs6585194
      polymorphisms were independently associated with HD after adjustment of clinical
      factors. The TCF7L2 rs290487 C/C variant homozygote showed much higher insulin
      resistance and significantly increased HD risk comparing with T/T and T/C
      genotypes, while the genetic variant of rs6585194 was protectively against HD.
      Three SNPs (rs290481, rs290487 and rs290489) located near the 3' end of TCF7L2
      gene were associated with HCC risk with marginal significance. Patients carrying
      G-C-A haplotype had a significantly higher HCC risk than those with A-T-G.
      CONCLUSIONS: TCF7L2 polymorphisms were associated with HD and maybe cancer risk
      as well. Further studies with large samples are needed to verify these results.

PMID- 23558247
TI  - Analysis of new Matrilin-1 gene variants in a case-control study related to
      dental malocclusions in Equus asinus.
AB  - Prognathism and brachygnathism are craniofacial deformities that severely affect
      the health of human and vertebrates, such as donkeys. The multifactorial etiology
      of this disease makes the genetic analysis a powerful tool for its understanding
      and prevention of spreading these deformities. This study aims to contribute to
      the characterization of the genetic basis of prognathism and brachygnathism in
      donkeys, using the Zamorano-Leones donkey, an endangered Spanish breed, as a
      model. Matrilin-1 (MATN1) polymorphisms have been previously described as markers
      for mandibular prognathism in Korean and Japanese human populations. Genetic
      variations in MATN1 gene were sought, in order to verify its association in a
      case-control study, including 30 donkeys presenting brachygnathism, 30 donkeys
      presenting prognathism and 30 donkeys with normal occlusion phenotypes. One
      genetic variation (g503G > A) located in an intronic region of MATN1 gene was
      identified and characterized. Statistically significant differences were detected
      between the control group and prognathism cases, but no statistical significant
      results were found between the control group and the brachygnathism cases. These
      results support evidence for an important role of MATN1 on prognathism in the
      analyzed population with MATN1 genetic variation - 503G>A - having a protective
      effect. Further studies should be developed in order to understand the whole role
      of MATN1 and the mechanisms affected by its genetic variations.

PMID- 23558248
TI  - The alpaca agouti gene: genomic locus, transcripts and causative mutations of
      eumelanic and pheomelanic coat color.
AB  - The agouti gene encodes the agouti signaling protein (ASIP) which regulates
      pheomelanin and eumelanin synthesis in mammals. To investigate the role of agouti
      in coat color variation of alpaca, we characterized the agouti gene and
      identified three mutations potentially involved with the determinism of eumelanic
      and pheomelanic phenotypes. The exon-4 hosts the mutations g.3836C>T, g.3896G>A
      and g.3866_3923del57. Further analysis of these mutations revealed two genotypes
      for black animals. The reverse transcription analysis of mRNA purified from skin
      biopsies of alpaca revealed the presence of three transcripts with different 5'
      untranslated regions (UTRs) and color specific expression. The white specific
      transcript, possibly originating from a duplication event (intra-chromosomal
      recombination) of the agouti gene is characterise by a 5'UTR containing 142bp of
      the NCOA6 gene sequence. Furthermore, the relative level expression analysis of
      mRNA demonstrates that the agouti gene has up-regulated expression in white skin,
      suggesting a pleiotropic effect of agouti in the white phenotype. Our findings
      refine the structure of the agouti locus and transcripts and provide additional
      information in order to understand the role of agouti in the pigmentation of
      alpaca.

PMID- 23558250
TI  - Agaricus bisporus genome sequence: a commentary.
AB  - The genomes of two isolates of Agaricus bisporus have been sequenced recently.
      This soil-inhabiting fungus has a wide geographical distribution in nature and it
      is also cultivated in an industrialized indoor process ($4.7bn annual worldwide
      value) to produce edible mushrooms. Previously this lignocellulosic fungus has
      resisted precise econutritional classification, i.e. into white- or brown-rot
      decomposers. The generation of the genome sequence and transcriptomic analyses
      has revealed a new classification, 'humicolous', for species adapted to grow in
      humic-rich, partially decomposed leaf material. The Agaricus biporus genomes
      contain a collection of polysaccharide and lignin-degrading genes and more
      interestingly an expanded number of genes (relative to other lignocellulosic
      fungi) that enhance degradation of lignin derivatives, i.e. heme-thiolate
      peroxidases and beta-etherases. A motif that is hypothesized to be a promoter
      element in the humicolous adaptation suite is present in a large number of genes
      specifically up-regulated when the mycelium is grown on humic-rich substrate. The
      genome sequence of A. bisporus offers a platform to explore fungal biology in
      carbon-rich soil environments and terrestrial cycling of carbon, nitrogen,
      phosphorus and potassium.

PMID- 23558249
TI  - Osteogenesis-inducing calcium phosphate nanoparticle precursors applied to
      titanium surfaces.
AB  - This study investigated the effects of the morphology and physicochemical
      properties of calcium phosphate (CaP) nanoparticles on osteogenesis. Two types of
      CaP nanoparticles were compared, namely amorphous calcium phosphate (ACP) nano
      spheres (diameter: 9-13 nm) and poorly crystalline apatite (PCA) nano-needles (30
      50 nm * 2-4 nm) that closely resemble bone apatite. CaP particles were spin
      coated onto titanium discs and implants; they were evaluated in cultured mouse
      calvarial osteoblasts, as well as after implantation in rabbit femurs. A
      significant dependence of CaP coatings was observed in osteoblast-related gene
      expression (Runx2, Col1a1 and Spp1). Specifically, the PCA group presented an up
      regulation of the osteospecific genes, while the ACP group suppressed the Runx2
      and Col1a1 expression when compared to blank titanium substrates. Both the ACP
      and PCA groups presented a more than three-fold increase of calcium deposition,
      as suggested by Alizarin red staining. The removal torque results implied a
      slight tendency in favour of the PCA group. Different forms of CaP nanostructures
      presented different biologic differences; the obtained information can be used to
      optimize surface coatings on biomaterials.

PMID- 23558251
TI  - Advancing the management of childhood epilepsies.
AB  - Childhood epilepsies comprise a heterogeneous group of disorders and syndromes
      that vary in terms of severity, prognosis and treatment requirements. Effective
      management requires early, accurate recognition and diagnosis, and a holistic
      approach that addresses each individual's medical and psychosocial needs within
      the context of their overall health status and quality of life. With increasing
      understanding of underlying aetiologies, new approaches to management and
      treatment are emerging. For example, genetic testing is beginning to provide a
      tool to aid differential diagnosis and a means of predicting predisposition to
      particular types of epilepsy. Despite the availability of an increasing number of
      antiepileptic drugs (AEDs)--due not only to the development of new AEDs, but also
      to changes in regulatory requirements that have facilitated clinical development-
      seizure control and tolerability continue to be suboptimal in many patients, and
      there is therefore a continuing need for new treatment strategies. Surgery and
      other non-pharmacological treatments (e.g. vagus nerve stimulation, ketogenic
      diet) are already relatively well established in paediatric epilepsy. New
      pharmacological treatments include generational advances on existing AEDs and
      AEDs with novel modes of action, and non-AED pharmacological interventions, such
      as immunomodulation. Emerging technologies include novel approaches allowing the
      delivery of medicinal agents to specific areas of the brain, and 'closed-loop'
      experimental devices employing algorithms that allow treatment (e.g., electrical
      stimulation) to be targeted both spatially and temporally. Although in early
      stages of development, cell-based approaches (e.g., focal targeting of adenosine
      augmentation) and gene therapy may also provide new treatment choices in the
      future.

PMID- 23558252
TI  - Systematic survey of natural radioactivity of soil in Slovenia.
AB  - Soil samples, from 70 points uniformly distributed over entire Slovenia, were
      analysed for (40)K, (232)Th and (226)Ra using gamma spectrometry, and for (234)U
      and (238)U using alpha spectrometry. The following ranges and averages of
      activity concentrations (Bq kg(-1)) were obtained: 98-2600 and 800 +/- 520 for
      (40)K, 9-170 and 77 +/- 33 for (232)Th, 12-270 and 63 +/- 44 for (226)Ra, 12-84
      and 34 +/- 19 for (234)U, and 11-90 and 34 +/- 19 for (238)U. With respect to
      lithology, the highest average values for (40)K and (232)Th were found at clastic
      sediments containing clay and for (226)Ra on carbonate rocks. Based on the
      measured activity concentrations, terrestrial gamma dose rates were calculated.
      The total dose rate ranged from 15 to 260 nGy h(-1), with arithmetic mean of 110
      +/- 49 nGy h(-1), being the highest over carbonates.

PMID- 23558253
TI  - The association of low socioeconomic status and the risk of having a child with
      Down syndrome: a report from the National Down Syndrome Project.
AB  - PURPOSE: Advanced maternal age and altered recombination are known risk factors
      for Down syndrome cases due to maternal nondisjunction of chromosome 21, whereas
      the impact of other environmental and genetic factors is unclear. The aim of this
      study was to investigate an association between low maternal socioeconomic status
      and chromosome 21 nondisjunction. METHODS: Data from 714 case and 977 control
      families were used to assess chromosome 21 meiosis I and meiosis II
      nondisjunction errors in the presence of three low socioeconomic status factors:
      (i) both parents had not completed high school, (ii) both maternal grandparents
      had not completed high school, and (iii) an annual household income of <$25,000.
      We applied logistic regression models and adjusted for covariates, including
      maternal age and race/ethnicity. RESULTS: As compared with mothers of controls (n
      = 977), mothers with meiosis II chromosome 21 nondisjunction (n = 182) were more
      likely to have a history of one low socioeconomic status factor (odds ratio =
      1.81; 95% confidence interval = 1.07-3.05) and >=2 low socioeconomic status
      factors (odds ratio = 2.17; 95% confidence interval = 1.02-4.63). This
      association was driven primarily by having a low household income (odds ratio =
      1.79; 95% confidence interval = 1.14-2.73). The same statistically significant
      association was not detected among maternal meiosis I errors (odds ratio = 1.31;
      95% confidence interval = 0.81-2.10), in spite of having a larger sample size (n
      = 532). CONCLUSION: We detected a significant association between low maternal
      socioeconomic status and meiosis II chromosome 21 nondisjunction. Further studies
      are warranted to explore which aspects of low maternal socioeconomic status, such
      as environmental exposures or poor nutrition, may account for these results.

PMID- 23558255
TI  - ACMG statement on noninvasive prenatal screening for fetal aneuploidy.
AB  - Noninvasive assessment of the fetal genome is now possible using next-generation
      sequencing technologies. The isolation of fetal DNA fragments from maternal
      circulation in sufficient quantity and sizes, together with proprietary
      bioinformatics tools, now allows patients the option of noninvasive fetal
      aneuploidy screening. However, obstetric care providers must become familiar with
      the advantages and disadvantages of the utilization of this approach as analysis
      of cell-free fetal DNA moves into clinical practice. Once informed, clinicians
      can provide efficient pretest and posttest counseling with the goal of avoiding
      patient harm. It is in the public's best interest that test results contain key
      elements and that laboratories adhere to established quality control and
      proficiency testing standards. The analysis of cell-free fetal DNA in maternal
      circulation for fetal aneuploidy screening is likely the first of major steps
      toward the eventual application of whole fetal genome/whole fetal exome
      sequencing.

PMID- 23558254
TI  - Description and pilot results from a novel method for evaluating return of
      incidental findings from next-generation sequencing technologies.
AB  - PURPOSE: The aim of this study was to develop, operationalize, and pilot test a
      transparent, reproducible, and evidence-informed method to determine when to
      report incidental findings from next-generation sequencing technologies. METHODS:
      Using evidence-based principles, we proposed a three-stage process. Stage I
      "rules out" incidental findings below a minimal threshold of evidence and is
      evaluated using inter-rater agreement and comparison with an expert-based
      approach. Stage II documents criteria for clinical actionability using a
      standardized approach to allow experts to consistently consider and recommend
      whether results should be routinely reported (stage III). We used expert opinion
      to determine the face validity of stages II and III using three case studies. We
      evaluated the time and effort for stages I and II. RESULTS: For stage I, we
      assessed 99 conditions and found high inter-rater agreement (89%), and strong
      agreement with a separate expert-based method. Case studies for familial
      adenomatous polyposis, hereditary hemochromatosis, and alpha1-antitrypsin
      deficiency were all recommended for routine reporting as incidental findings. The
      method requires <3 days per topic. CONCLUSION: We establish an operational
      definition of clinically actionable incidental findings and provide documentation
      and pilot testing of a feasible method that is scalable to the whole genome.

PMID- 23558256
TI  - Density matters: comparison of array platforms for detection of copy-number
      variation and copy-neutral abnormalities.
AB  - PURPOSE: A combination of oligonucleotide and single-nucleotide polymorphism
      probes on the same array platform can detect copy-number abnormalities and copy
      neutral aberrations such as uniparental disomy and long stretches of
      homozygosity. The single-nucleotide polymorphism probe density in commercially
      available platforms varies widely, which may affect the detection of copy-neutral
      abnormalities. METHODS: We evaluated the ability of array platforms with low
      (Oxford Gene Technology CytoSure ISCA uniparental disomy), mid-range (Agilent
      custom array), and high (Affymetrix CytoScan HD) single-nucleotide polymorphism
      probe density to detect copy-number variation, mosaicism, uniparental isodisomy,
      and absence of heterozygosity in 50 clinical samples. RESULTS: All platforms
      reliably detected copy-number variation, mosaicism, and uniparental isodisomy;
      however, absence-of-heterozygosity detection varied significantly. The low
      density array called absence-of-heterozygosity regions not confirmed by the other
      platforms and also overestimated the length of true absence-of-heterozygosity
      regions. Furthermore, the low- and mid-density platforms failed to detect some
      small absence-of-heterozygosity regions that were identified by the high-density
      platform. CONCLUSION: Variation in single-nucleotide polymorphism density can
      lead to major discrepancies in the detection of and confidence in copy-neutral
      abnormalities. Although suitable for uniparental disomy detection, copy-number
      plus single-nucleotide polymorphism arrays with 30,000 or fewer unique single
      nucleotide polymorphism probes miscall absence-of-heterozygosity regions due to
      identity by descent.

PMID- 23558257
TI  - Liver transplantation in acute-on-chronic liver failure patients with high model
      for end-stage liver disease (MELD) scores: a single center experience of 100
      consecutive cases.
AB  - BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical condition
      for which liver transplantation (LT) is the only curative option. However, there
      are little published data on risk factors and outcomes of LT for ACLF. METHODS:
      The objective of this study was to analyze preoperative, intraoperative,
      postoperative, and overall survival data on 100 consecutive cases with ACLF in
      order to try to determine for which patients LT are futile. RESULTS: One hundred
      consecutive patients with pathology-confirmed ACLF who underwent LT from June
      2004 to September 2012 were enrolled. The preoperative data showed that all
      patients were in a serious condition with a median high model for end-stage liver
      disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international
      normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed
      by a Sequential Organ Failure Assessment (SOFA) score of >=9. The patients had
      either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3
      , and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%,
      respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%,
      72.1%, and 70.6%, respectively. However, the area under receiver operating
      characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552,
      0.547, and 0.547, respectively. CONCLUSIONS: Both deceased and living donor LT
      are effective therapeutic options for patients with ACLF and the short- and long
      term survival rates are encouraging. It is important to conduct more prospective
      and multi-center studies to define preoperatively which patients would benefit
      from LT.

PMID- 23558259
TI  - Efficient CO-CA transfer in highly deuterated proteins by band-selective
      homonuclear cross-polarization.
AB  - Robust and efficient band-selective magnetization transfer between CO and CA
      spins can be achieved in highly deuterated solid proteins by dipolar-based
      homonuclear cross polarization. The approach is designed for moderate magic-angle
      spinning rates and high external magnetic fields where the isotropic chemical
      shift difference of CO and CA considerably exceeds the spinning rate. The most
      efficient recoupling is achieved when the sum of effective radio-frequency fields
      on CO and CA resonances equals two times the spinning rate. This method can be
      directly implemented in proton-detected versions of inter-residual correlation
      experiments as needed for resonance assignment in protein solid-state NMR
      spectroscopy.

PMID- 23558258
TI  - BML-111 attenuates hemorrhagic shock-induced acute lung injury through inhibiting
      activation of mitogen-activated protein kinase pathway in rats.
AB  - BACKGROUND: Hemorrhagic shock activates cellular stress signals and can lead to
      systemic inflammatory response, organ injury, and death. Mitogen-activated
      protein kinase (MAPK) acts as a sensor of tissue injury in models of ischemia
      reperfusion injury. Lipoxins are endogenous lipid mediators with potent anti
      inflammatory and pro-resolving actions. We hypothesized that BML-111 (a lipoxin
      A4-receptor agonist) attenuates hemorrhagic shock-induced acute lung injury (ALI)
      through inhibiting activation of the MAPK pathway. METHODS: We randomized Sprague
      Dawley rats into four groups: sham, hemorrhagic shock-resuscitation (HS), HS plus
      BML-111 (BML-111), and HS plus BML-111 and BOC-2 (BOC-2). Two hours after
      resuscitation, we collected samples of lung. We obtained bronchoalveolar lavage
      fluid for neutrophil count. We performed optical microscopy to examine pathologic
      changes in lungs. Wet/dry ratios, myeloperoxidase expression, interleukin (IL)
      1beta and IL-6 levels in lung were measured. We evaluated MAPK activation and the
      DNA binding activity of activator protein-1 in lung. RESULTS: Treatment with BML
      111 reduced the lung damage and wet/dry ratio, neutrophil count in
      bronchoalveolar lavage fluid, expression of myeloperoxidase, and production of IL
      1beta and IL-6 in lung. Phosphorylation of MAPK was also decreased by BML-111 in
      lung. Furthermore, the DNA binding activity of activator protein-1 was blocked by
      BML-111. An antagonist of the lipoxin A4-receptor, BOC-2, reversed the protective
      effect of BML-111 on ALI induced by hemorrhagic shock. CONCLUSIONS: This study
      indicates that BML-111 attenuated hemorrhagic shock-induced ALI via the
      MAPK/activator protein-1 signaling pathway. Therefore, BML-111 may have
      therapeutic potential for hemorrhagic shock-induced ALI.

PMID- 23558260
TI  - Unifying complexity and information.
AB  - Complex systems, arising in many contexts in the computer, life, social, and
      physical sciences, have not shared a generally-accepted complexity measure
      playing a fundamental role as the Shannon entropy H in statistical mechanics.
      Superficially-conflicting criteria of complexity measurement, i.e. complexity
      randomness (C-R) relations, have given rise to a special measure intrinsically
      adaptable to more than one criterion. However, deep causes of the conflict and
      the adaptability are not much clear. Here I trace the root of each representative
      or adaptable measure to its particular universal data-generating or -regenerating
      model (UDGM or UDRM). A representative measure for deterministic dynamical
      systems is found as a counterpart of the H for random process, clearly redefining
      the boundary of different criteria. And a specific UDRM achieving the intrinsic
      adaptability enables a general information measure that ultimately solves all
      major disputes. This work encourages a single framework coving deterministic
      systems, statistical mechanics and real-world living organisms.

PMID- 23558261
TI  - Anionic porphyrin-grafted porous silicon nanoparticles for photodynamic therapy.
AB  - Non-toxic porous silicon nanoparticles carry porphyrin covalently attached to
      their surface inside breast cancer cells for a more efficient photodynamic
      effect.

PMID- 23558262
TI  - International comparisons of the technical efficiency of the hospital sector:
      panel data analysis of OECD countries using parametric and non-parametric
      approaches.
AB  - There is a growing interest in the cross-country comparisons of the performance
      of national health care systems. The present work provides a comparison of the
      technical efficiency of the hospital sector using unbalanced panel data from OECD
      countries over the period 2000-2009. The estimation of the technical efficiency
      of the hospital sector is performed using nonparametric data envelopment analysis
      (DEA) and parametric stochastic frontier analysis (SFA). Internal and external
      validity of findings is assessed by estimating the Spearman rank correlations
      between the results obtained in different model specifications. The panel-data
      analyses using two-step DEA and one-stage SFA show that countries, which have
      higher health care expenditure per capita, tend to have a more technically
      efficient hospital sector. Whether the expenditure is financed through private or
      public sources is not related to the technical efficiency of the hospital sector.
      On the other hand, the hospital sector in countries with higher income inequality
      and longer average hospital length of stay is less technically efficient. 

PMID- 23558263
TI  - The Candida albicans Hwp2p can complement the lack of filamentation of a
      Saccharomyces cerevisiae flo11 null strain.
AB  - The opportunistic fungal pathogen Candida albicans is one of the leading agents
      of life-threatening infections affecting immunocompromised individuals. Many
      factors make C. albicans a successful pathogen. These include the ability to
      switch between yeast and invasive hyphal morphologies in addition to an arsenal
      of cell wall virulence factors such as lipases, proteases, dismutases and
      adhesins that promote the attachment to the host, a prerequisite for invasive
      growth. We have previously characterized Hwp2, a C. albicans cell wall protein
      which we found necessary for proper oxidative stress, biofilm formation and
      adhesion to host cells. Baker's yeast Saccharomyces cerevisiae also possesses
      adhesins that promote aggregation and flocculence. Flo11 is one such adhesin that
      has sequence similarity to Hwp2. Here we determined that transforming an HWP2
      cassette can complement the lack of filamentation of an S. cerevisiae flo11 null
      strain and impart on S. cerevisiae adhesive properties similar to those of a
      pathogen.

PMID- 23558264
TI  - Inactivation of the LysR regulator Cj1000 of Campylobacter jejuni affects host
      colonization and respiration.
AB  - Transcriptional regulation mediates adaptation of pathogens to environmental
      stimuli and is important for host colonization. The Campylobacter jejuni genome
      sequence reveals a surprisingly small set of regulators, mostly of unknown
      function, suggesting an intricate regulatory network. Interestingly, C. jejuni
      lacks the homologues of ubiquitous regulators involved in stress response found
      in many other Gram-negative bacteria. Nonetheless, cj1000 is predicted to encode
      the sole LysR-type regulator in the C. jejuni genome, and thus may be involved in
      major adaptation pathways. A cj1000 mutant strain was constructed and found to be
      attenuated in its ability to colonize 1-day-old chicks. Complementation of the
      cj1000 mutation restored the colonization ability to wild-type levels. The mutant
      strain was also outcompeted in a competitive colonization assay of the piglet
      intestine. Oxygraphy was carried out for what is believed to be the first time
      with the Oroboros Oxygraph-2k on C. jejuni and revealed a role for Cj1000 in
      controlling O2 consumption. Furthermore, microarray analysis of the cj1000 mutant
      revealed both direct and indirect regulatory targets, including genes involved in
      energy metabolism and oxidative stress defences. These results highlight the
      importance of Cj1000 regulation in host colonization and in major physiological
      pathways.

PMID- 23558265
TI  - Levels of control exerted by the Isc iron-sulfur cluster system on biosynthesis
      of the formate hydrogenlyase complex.
AB  - The membrane-associated formate hydrogenlyase (FHL) complex of bacteria like
      Escherichia coli is responsible for the disproportionation of formic acid into
      the gaseous products carbon dioxide and dihydrogen. It comprises minimally seven
      proteins including FdhF and HycE, the catalytic subunits of formate dehydrogenase
      H and hydrogenase 3, respectively. Four proteins of the FHL complex have iron
      sulphur cluster ([Fe-S]) cofactors. Biosynthesis of [Fe-S] is principally
      catalysed by the Isc or Suf systems and each comprises proteins for assembly and
      for delivery of [Fe-S]. This study demonstrates that the Isc system is essential
      for biosynthesis of an active FHL complex. In the absence of the IscU assembly
      protein no hydrogen production or activity of FHL subcomponents was detected. A
      deletion of the iscU gene also resulted in reduced intracellular formate levels
      partially due to impaired synthesis of pyruvate formate-lyase, which is dependent
      on the [Fe-S]-containing regulator FNR. This caused reduced expression of the
      formate-inducible fdhF gene. The A-type carrier (ATC) proteins IscA and ErpA
      probably deliver [Fe-S] to specific apoprotein components of the FHL complex
      because mutants lacking either protein exhibited strongly reduced hydrogen
      production. Neither ATC protein could compensate for the lack of the other,
      suggesting that they had independent roles in [Fe-S] delivery to complex
      components. Together, the data indicate that the Isc system modulates FHL complex
      biosynthesis directly by provision of [Fe-S] as well as indirectly by influencing
      gene expression through the delivery of [Fe-S] to key regulators and enzymes that
      ultimately control the generation and oxidation of formate.

PMID- 23558266
TI  - Development of pyloric stenosis after a 4-day course of oral erythromycin.
AB  - Early exposure to oral erythromycin in young infants, particularly in the first 2
      weeks of life, has previously been associated with the development of
      hypertrophic pyloric stenosis. We report a case of an infant who received an
      abbreviated 4-day course of oral erythromycin for suspected Chlamydia
      conjunctivitis at 5 days of life then underwent pyloromyotomy for pyloric
      stenosis less than 2 weeks later. Health care providers should use erythromycin
      judiciously in neonates because only a few days of exposure to this medication
      may lead to the development of a surgical condition of gastric outlet
      obstruction.

PMID- 23558267
TI  - Intestinal obstruction in children: could it be congenital abdominal bands?
AB  - Chronic abdominal pain is the most commonly seen condition in the pediatric
      population. Many causes can be successfully managed by conservative treatment;
      nevertheless, surgical intervention is sometimes inevitable. Among many surgical
      conditions, such as appendicitis as the most frequent cause, one is also to think
      about congenital abdominal bands. We report a case of a 10-year-old boy with
      chronic abdominal pain, who suddenly developed clinical and radiologic signs of
      intestinal obstruction. The cause of chronic abdominal pain as well as the
      intestinal obstruction was revealed during the operation: 2 congenital abdominal
      bands, trapping the gut convolutes. To our knowledge, this is the first report of
      2 bands in a single patient.

PMID- 23558268
TI  - Hydrogen peroxide solution ingestion caused brain death of a 3-year-old girl.
AB  - Hydrogen peroxide solutions are often used in daily life as a household
      disinfectant and in cosmetic products and are therefore a common source of
      intentional poisonings, especially for children. When ingested in small amounts,
      it may cause severe central nervous system damage as a result of arterial emboli
      like our case. The benefit of hyperbaric oxygen treatment in this situation is
      known, but the neurologic deficits of our case did not improve with this method
      and finally brain death occurred. This is may be related by the timing of
      treatment after the event. We would like to emphasize that every clinician must
      be aware of the dangers of hydrogen peroxide ingestion and hyperbaric oxygen
      treatment may be of benefit if it is performed immediately.

PMID- 23558269
TI  - Pediatrician! Do you know the symptoms of DRESS syndrome? A case report of a 4
      year-old girl.
AB  - Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe
      drug-induced hypersensitivity syndrome and may be observed after administration
      of many drugs. Clinical symptoms usually occur 2 to 8 weeks after drug
      introduction. Because DRESS syndrome is potentially life threatening, it is
      especially important to diagnose it early. Withdrawal of the drug which induced
      symptoms is the most important therapeutic option. DRESS syndrome appears mostly
      in adults. There are relatively few articles on the DRESS syndrome in children.
      The article presents a case of a 4-year-old girl with a life-threatening clinical
      course of DRESS syndrome with massive pulmonary involvement. The knowledge of
      DRESS syndrome clinical symptoms is essential for doctors of various specialties.
      It is especially important that general practitioners, pediatricians, and
      pediatric neurologists should be able to take this life-threatening syndrome into
      consideration for differential diagnosis.

PMID- 23558270
TI  - Spontaneous pneumorrhachis.
AB  - Pneumomediastinum is a relatively uncommon occurrence in pediatric patients.
      After mediastinal air leak, air may dissect through a variety of tissue planes
      within the chest, neck, and abdomen. We report the case of a 16-year-old
      adolescent boy who presented with spontaneous pneumomediastinum accompanied by
      the presence of air within the spinal canal. We suggest use of the term
      "spontaneous pneumorrhachis" to distinguish this type of presentation from other
      potential causes.

PMID- 23558271
TI  - Rectum perforation after broomstick impalement in a 17-year-old: case report and
      review.
AB  - Impalement injuries are uncommon, especially in the pediatric population. Because
      of the rarity of these injuries, physicians may have difficulty recognizing and
      treating impalement injuries appropriately. Clinical findings are sometimes
      innocuous, but can be life threatening. Therefore, evaluation of suspected
      impalement injury should involve careful history and thorough physical
      examination, even if there is no evidence of trauma to the perineum. We report a
      very rare case of rectum perforation after transanal introduction of a broomstick
      with almost no clinical findings. Impalement injuries are difficult to recognize,
      and severity may not be reflected by their external appearance. To diagnose these
      injuries in time, it is important to use a well-organized workup.

PMID- 23558272
TI  - Fever and bulging fontanelle mimicking meningitis in an infant diagnosed with
      benign intracranial hypertension.
AB  - A previously healthy 7-month-old male presented to the emergency department with
      fever and a bulging anterior fontanelle. A computed tomographic scan of the head
      suggested mild communicating hydrocephalus. Lumbar puncture was performed, which
      revealed a normal cerebrospinal fluid (CSF) cell count and glucose concentration,
      but a markedly elevated opening pressure. DNA polymerase chain reaction for
      herpes simplex virus performed on CSF was negative; CSF bacterial cultures were
      without growth. DNA polymerase chain reaction for human herpes virus 6 was
      strongly positive in serum. Fever and bulging fontanelle resolved within 24
      hours. A presumptive diagnosis of transient intracranial hypertension of infancy
      was made, a form of benign idiopathic intracranial hypertension that mimics the
      presentation of serious intracranial pathology.

PMID- 23558273
TI  - Tracheal foreign bodies: are radiographs misleading?
AB  - OBJECTIVE: This study aimed to highlight the pitfalls of relying on radiographs
      in identifying potentially life-threatening upper airway foreign bodies in
      children. DESIGN: Case series. METHODS: A review of the medical records of 2
      cases of upper tracheal foreign body was performed. RESULTS: Both patients
      presented with biphasic stridor refractory to medical therapy and chest
      radiographs that were normal. One patient had a history of witnessed aspiration
      while the other did not. Both patients were managed by endoscopic removal of
      foreign bodies in the operating room and experienced no long-term sequelae
      related to this event. CONCLUSIONS: Tracheal foreign bodies present a diagnostic
      challenge, and patients may fail to manifest radiographic abnormalities. In
      patients with a characteristic history and biphasic stridor, an endoscopic
      evaluation of the airway should be performed to avoid potentially devastating
      consequences.

PMID- 23558274
TI  - Twist and shout! Pediatric ovarian torsion clinical update and case discussion.
AB  - Ovarian torsion (OT) in the pediatric patient is an uncommon event and a
      challenging diagnosis. Clinicians caring for children in the acute setting should
      be aware of the symptoms and the diagnostic findings of OT. All patients
      suspected to have OT require consultation with gynecology; however, there is some
      controversy regarding the best operative intervention. In this article, case
      discussions will serve as a platform for discussing the epidemiology and clinical
      manifestations of pediatric OT, as well as reviewing the latest evidence related
      to the diagnosis and treatment.

PMID- 23558276
TI  - Recognition and management of pediatric food allergy in the emergency department.
AB  - Recently, the National Institute of Allergy and Infectious Diseases sought to
      establish consistency in definitions, diagnostic criteria, and management
      practices concerning food allergies (FAs). This review aimed to summarize and
      highlight the relevant findings of these guidelines for the emergency department
      provider, as pediatric patients often present to the emergency department with
      FAs or other disorders mimicking FAs.

PMID- 23558277
TI  - Identification of unanticipated pelvic pathology on renal bedside ultrasound.
AB  - Bedside emergency ultrasound can be a useful initial test in children who present
      with abdominal pain. Our case describes a teenager who presented to the emergency
      department with back pain and right lower quadrant pain, suspicious for
      nephrolithiasis. The use of bedside ultrasound enabled timely diagnosis and
      management of an unanticipated condition.

PMID- 23558279
TI  - Pediatric emergency medicine: legal briefs.

PMID- 23558280
TI  - ECGs in the ED.

PMID- 23558281
TI  - Seat belts and traffic accidents are major causes of pediatric blunt
      gastrointestinal injury: outcomes in a Level 1 pediatric trauma center in
      Austria.

PMID- 23558282
TI  - Predictive value of S-100beta protein for prognosis in patients with moderate and
      severe traumatic brain injury: systematic review and meta-analysis.
AB  - OBJECTIVES: To determine the ability and accuracy of the S-100beta protein in
      predicting prognosis after a moderate or severe traumatic brain injury. DESIGN:
      Systematic review and meta-analysis of randomised controlled trials and
      observational studies. DATA SOURCES: Medline, Embase, Cochrane Central Register
      of Controlled Trials, BIOSIS (from their inception to April 2012), conference
      abstracts, bibliographies of eligible articles, and relevant narrative reviews.
      STUDY SELECTION: Two reviewers independently reviewed citations and selected
      eligible studies, defined as cohort studies or randomised control trials
      including patients with moderate or severe traumatic brain injury and evaluating
      the prognostic value of S-100beta protein. Outcomes evaluated were mortality,
      score on the Glasgow outcome scale, or brain death. DATA EXTRACTION: Two
      independent reviewers extracted data using a standardised form and evaluated the
      methodological quality of included studies. Pooled results were presented with
      geometric means ratios and analysed with random effect models. Prespecified
      sensitivity analyses were performed to explain heterogeneity. RESULTS: The search
      strategy yielded 9228 citations. Two randomised controlled trials and 39 cohort
      studies were considered eligible (1862 patients). Most studies (n=23) considered
      Glasgow outcome score <= 3 as an unfavourable outcome. All studies reported at
      least one measurement of S-100beta within 24 hours after traumatic brain injury.
      There was a significant positive association between S-100beta protein
      concentrations and mortality (12 studies: geometric mean ratio 2.55, 95%
      confidence interval 2.02 to 3.21, I(2)=56%) and score <= 3 (18 studies: 2.62,
      2.01 to 3.42, I(2)=79%). Sensitivity analysis based on sampling time, sampling
      type, blinding of outcome assessors, and timing of outcome assessment yielded
      similar results. Thresholds for serum S-100beta protein values with 100%
      specificity ranged from 1.38 to 10.50 ug/L for mortality (six studies) and from
      2.16 to 14.00 ug/L for unfavourable neurological prognosis as defined by the
      Glasgow outcome score. CONCLUSIONS: After moderate or severe traumatic brain
      injury, serum S-100beta protein concentrations are significantly associated with
      unfavourable prognosis in the short, mid, or long term. Optimal thresholds for
      discrimination remain unclear. Measuring the S-100beta protein could be useful in
      evaluating the severity of traumatic brain injury and in the determination of
      long term prognosis in patients with moderate and severe injury.

PMID- 23558283
TI  - Doctor who lied on his CV is allowed to return to work.

PMID- 23558284
TI  - US to launch major brain research initiative.

PMID- 23558286
TI  - Lymphatic malformations of the airway.
AB  - OBJECTIVES/HYPOTHESIS: To characterize the anatomic distribution of lymphatic
      malformations of the upper airway. STUDY DESIGN: Case series with chart review.
      SETTING: Tertiary care referral center specializing in the diagnosis and
      treatment of vascular anomalies. METHODS: A 7-year (2004-2011) retrospective
      chart review of patients with lymphatic malformations was performed at a tertiary
      care referral center. Patients with airway lymphatic malformations were
      identified. The anatomic distribution of lymphatic malformations within the
      airway was reviewed. RESULTS: A total of 141 patients with lymphatic
      malformations of the upper aerodigestive tract (UADT) were studied. Of these, 15
      (11%) had laryngeal (supraglottic) involvement. In all of these patients, the
      disease was above the true vocal folds. Seventy-four (52%) patients had
      involvement of 1 anatomic zone (most common was the oral cavity), and 67 (48%)
      had involvement of multiple zones. With regard to each zone, 105 (75%) patients
      had involvement of the oral cavity, 50 (36%) the oropharynx, 8 (6%) the
      hypopharynx, 42 (30%) the parapharynx, and 12 (9%) had retropharygeal disease
      (some patients had multiple zones involved). No patients were identified with
      glottic, subglottic, or tracheal involvement. CONCLUSIONS: Based on our large
      series, airway involvement in head and neck lymphatic malformations may occur at
      multiple sites above the glottis. A high percentage of these patients have
      involvement of the oral cavity (75%) and oropharynx (35%). None involve the
      glottis, subglottis, or trachea.

PMID- 23558287
TI  - Malignant otitis externa: an Asian perspective on treatment outcomes and
      prognostic factors.
AB  - OBJECTIVE: Malignant otitis externa (MOE) is a severe disease with varying
      outcomes. Despite advances in antibiotic treatment, a significant proportion
      still succumbs to this disease. We aimed to analyze the effect of clinical
      factors on prognosis and to review treatment outcomes in our institution. STUDY
      DESIGN: Case series with retrospective chart review of MOE cases from 2006 to
      2011. SETTING: Department of Otolaryngology-Head and Neck Surgery, National
      University Hospital, Singapore, a tertiary referral center. SUBJECTS AND METHODS:
      Patients with MOE admitted for treatment were studied and divided into 2 outcome
      groups depending on response to a 6-week course of intravenous antibiotics.
      Demographic and disease factors were analyzed with regard to outcome. RESULTS:
      Nineteen cases were analyzed. Disease resolved in 63.2% after 6 weeks of
      antibiotics. Mortality was 21.1%. Age, diabetic control, duration of diagnostic
      delay, cranial nerve involvement, and inflammatory markers were not found to
      predict prognosis. Erythrocyte sedimentation rate and C-reactive protein levels
      correlated with disease activity and can be used to monitor progress. Clival
      involvement was associated with persistent disease (P = .002). Only 63.2% of
      cases had positive cultures. Pseudomonas aeruginosa was the main organism, and
      33.3% of isolates were multidrug resistant. Outcome was not different in cases
      where culture-directed therapy was employed vs those where empirical ceftazidime
      and fluoroquinolone were used (P = .650). CONCLUSION: Malignant otitis externa
      remains an insidious disease with significant mortality. Involvement of the
      clivus portends a poorer prognosis. Combination therapy with intravenous
      ceftazidime and oral fluoroquinolone remains relevant despite concerns of culture
      negative cases and multidrug-resistant Pseudomonas.

PMID- 23558285
TI  - In vitro evaluation of sialyl Lewis X relationship with head and neck cancer stem
      cells.
AB  - OBJECTIVE: To evaluate in vitro the potential links between sialyl Lewis X (sLeX)
      and cancer stem cells (CSC) in head and neck squamous cell carcinoma (HNSCC).
      HNSCC is an aggressive malignancy with high mortality mainly due to metastasis.
      CSC have emerged as important players in HNSCC metastasis. sLeX is a
      tetrasaccharide carbohydrate known to play a key role in metastatic dissemination
      by promoting binding of the tumor cells to the endothelium. STUDY DESIGN:
      Experimental, in vitro. SETTING: Laboratory of Head and Neck Cancer Metastasis,
      University of Michigan. SUBJECTS AND METHODS: A panel of stage- and anatomic-site
      specific primary and metastatic HNSCC cell lines was assessed by flow cytometry
      to quantify sLeX relative expression levels. Serum-free conditioned media from
      the same HNSCC lines was collected over a time course of 72 hours and assessed by
      Western blot for secreted sLeX expression. Representative HNSCC cell lines were
      cultured as floating orospheres (condition that enhance CSC growth) or under
      normal adherent conditions and characterized by flow cytometry for CSC markers
      (CD44, aldehyde dehydrogenase [ALDH]) comparatively with sLeX expression.
      RESULTS: sLeX is predominantly expressed in carcinomas originating from the oral
      cavity. Secreted sLeX is also found to be high in oral carcinomas and increased
      over the analyzed time course. Floating orospheres were strongly positive for
      CD44 and ALDH, confirming CSC enrichment of the orospheres. Tumor cells grown as
      orospheres are 95% to 100% positive for sLeX compared to 10% to 40% of adherent
      counterpart. CONCLUSION: These studies provide the first evidence of sLeX
      relationship with CSC in HNSCC.

PMID- 23558288
TI  - Proteolytic cleavage of LEDA-1/PIANP by furin-like proprotein convertases
      precedes its plasma membrane localization.
AB  - Liver endothelial differentiation-associated protein-1 (LEDA-1/PIANP) is a type-I
      transmembrane protein first identified by us as a putative junctional protein in
      liver sinusoidal endothelial cells. Others have shown that LEDA-1/PIANP binds and
      activates immune inhibitory receptor PILRalpha in trans, a process that requires
      sialidation of LEDA-1/PIANP. Here we show that LEDA-1/PIANP is subject to O
      glycosylation and sialidation as demonstrated in brain tissue as well as in LEDA
      1 expressing cell lines by using anti-LEDA-1/PIANP C-terminal antibodies. In
      addition, analysis of LEDA-1/PIANP processing with His-tags inserted at different
      positions in the extracellular domain revealed that multiple steps of proteolytic
      cleavage occur during maturation of the protein. Proteolytic cleavage between
      aa59 and aa83 preceded sorting of the protein to the plasma membrane. Deletion of
      aa75-79 and inhibition with Furin inhibitor I confirmed that LEDA-1/PIANP is
      processed by a Furin-like proprotein convertase. In summary, these findings show
      that Furin-like proprotein convertase-dependent processing precedes plasma
      membrane localization of LEDA-1/PIANP that is a pre-requisite of functional
      receptor-ligand interactions in vitro and in vivo.

PMID- 23558289
TI  - Identification and functional characterization of novel MATE1 genetic variations
      in Koreans.
AB  - Multidrug and toxin extrusion 1 (MATE1, SLC47A1), an organic cation transporter,
      plays an important role in the renal and biliary elimination of various clinical
      drugs, including the anti-diabetic drug metformin. The goal of this study was to
      identify and characterize novel genetic variants of MATE1. Five variants in the
      promoter region and two nonsynonymous variants, p.D64G and p.L125F, were
      identified in 48 DNA samples from healthy Koreans. MATE1 promoter haplotype 3
      containing g.-1975C>A showed a significant increase in reporter activity. Three
      transcription factors, Nkx-2.5, SREBP-1, and USF-1 were predicted to bind to the
      promoter in the region of g.-1975C>A. Results from electrophoretic mobility shift
      assays showed that the g.-1975A allele exhibits greater binding affinity to all
      of these transcription factors than the g.-1975C allele. In particular, we found
      that Nkx-2.5 and USF-1 induce MATE1 transcription. Our study suggests that the
      common promoter haplotype of MATE1 changes MATE1 transcriptional activity
      regulated by Nkx-2.5, SREBP-1, and USF-1.

PMID- 23558290
TI  - An interview by Dr. Ernesto Carafoli with Dr. Gottfried Schatz.

PMID- 23558292
TI  - Nonlinear spectro-temporal features based on a cochlear model for automatic
      speech recognition in a noisy situation.
AB  - A nonlinear speech feature extraction algorithm was developed by modeling human
      cochlear functions, and demonstrated as a noise-robust front-end for speech
      recognition systems. The algorithm was based on a model of the Organ of Corti in
      the human cochlea with such features as such as basilar membrane (BM), outer hair
      cells (OHCs), and inner hair cells (IHCs). Frequency-dependent nonlinear
      compression and amplification of OHCs were modeled by lateral inhibition to
      enhance spectral contrasts. In particular, the compression coefficients had
      frequency dependency based on the psychoacoustic evidence. Spectral subtraction
      and temporal adaptation were applied in the time-frame domain. With long-term and
      short-term adaptation characteristics, these factors remove stationary or slowly
      varying components and amplify the temporal changes such as onset or offset. The
      proposed features were evaluated with a noisy speech database and showed better
      performance than the baseline methods such as mel-frequency cepstral coefficients
      (MFCCs) and RASTA-PLP in unknown noisy conditions. 

PMID- 23558291
TI  - Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and
      cancer stem cell-like characteristics in colorectal cancer cells.
AB  - Increased cell migration and invasion lead to cancer metastasis and are crucial
      to cancer prognosis. In this study, we explore whether FBXW7 plays any role in
      metastatic process. We show that depletion of FBXW7 induces epithelial
      mesenchymal transition (EMT) in human colon cancer cells along with the increase
      in cell migration and invasion. Moreover, FBXW7 deficiency promotes the
      generation of colon cancer stem-like cells in tumor-sphere culture. mTOR
      inhibition by rapamycin suppresses FBXW7 loss-driven EMT, invasion and stemness.
      Our results define the FBXW7/mTOR axis as a novel EMT pathway that mediates
      cancer invasion.

PMID- 23558293
TI  - Cardiac ion channel trafficking defects and drugs.
AB  - Fine control over the functional expression of cardiac ion channels is required
      to maintain normal action potential (AP) duration and QTc times. A growing number
      of drugs interfere with normal trafficking of ion channels to and from the plasma
      membrane, thereby altering the number of channels on the cell surface. Most drugs
      do this at clinically relevant concentrations, which may lead to potentially life
      threatening cardiac arrhythmias. Recently, major progress has been made in the
      understanding of the subcellular mechanisms by which drugs affect the trafficking
      of ion channels, which is of great benefit for the development of ways to
      counteract these adverse drug effects. Pharmacological correction seems to be a
      promising approach to address the trafficking defects induced by several drugs.
      However, as pharmacological correction is hampered by concomitant direct channel
      block or unspecific effects, further studies are needed to improve its potential
      as a clinical therapy.

PMID- 23558294
TI  - Performance and ease of use evaluation of a new surgical post-operative foam
      island dressing in 14 patients undergoing elective gynaecological surgery.
AB  - AIM: The aim of this evaluation was to investigate ease of use and clinical
      performance of a new post-operative foam island dressing in female patients
      undergoing elective gynaecological surgery. Women undergoing surgery have genuine
      concerns regarding the risk of a hospital acquired infection. METHODOLOGY: The
      new post-operative dressing was evaluated on 14 patients undergoing elective
      gynaecological surgery during two weeks in March 2011. Evaluators rated packaging
      and dressing ease of use, wear time, shower proof ability, skin blistering and
      ease of removal. Patients rated comfort of the dressing during wear time and
      removal. RESULTS: Nurses and Midwives rated blister prevention 100% (good),
      shower proof capabilities 86% (good) and ease of removal 79% (good). Patients
      rated comfort during wear time, skin integrity, and the importance of bathing
      (shower proof). No wound infections, peri wound maceration or adverse events were
      recorded. CONCLUSION: Ensuring best patient outcomes and meeting individual needs
      remains the cornerstone of nursing practice. Reducing the risk of surgical site
      infections (SSI) remains a focus for NHS Trust throughout the UK particularly as
      Gynaelogical procedures require mandatory surveillance by the Health Protection
      Agency 1(The importance of patient comfort and ability to tend to hygiene needs
      is fundamental). The evaluated dressing has a flexible island pad allowing
      further tensile stretch and conformability when in situ. This was demonstrated in
      this study by both clinicians and patients in blister prevention, conformability,
      and patient comfort outcomes of this evaluation.

PMID- 23558295
TI  - Characterization of a gap-junctional intercellular communication (GJIC) assay
      using cigarette smoke.
AB  - Inhibition of gap-junctional intercellular communication (GJIC) via exposure to
      various toxic substances has been implicated in tumor promotion. In the present
      study, cigarette smoke total particulate matter (TPM), a known inhibitor of GJIC,
      were used to characterize a new GJIC screening assay in three independent
      experiments. The main features of this assay were automated fluorescence
      microscopy combined with non-invasive parachute technique. Rat liver epithelial
      cells (WB-F344) were stained with the fluorescent dye Calcein AM (acetoxymethyl)
      and exposed to TPM from the Kentucky Reference Cigarette 2R4F (a blend of Bright
      and Burley tobaccos) and from two single-tobacco cigarettes (Bright and Burley)
      for 3h. Phorbol-12-myristate-13-acetate (TPA) was used as positive control and
      0.5% dimethyl sulfoxide (DMSO) as solvent control. The transfer of dye to
      adjacent cells (percentage of stained cells) was used as a measure of cellular
      communication. A clear and reproducible dose-response of GJIC inhibition
      following TPM exposure was seen. Reproducibility and repeatability measurements
      for the 2R4F cigarette were 3.7% and 6.9%, respectively. The half-maximal
      effective concentration values were 0.34ng/ml for TPA, 0.050mg/ml for the 2R4F,
      0.044mg/ml for the Bright cigarette, and 0.060mg/ml for the Burley cigarette. The
      assay was able to discriminate between the two single-tobacco cigarettes
      (P<0.0001), and between the single-tobacco cigarettes and the 2R4F (P=0.0008,
      2R4F vs. Burley and P<0.0001, 2R4F vs. Bright). Thus, this assay can be used to
      determine the activity of complex mixtures such as cigarette smoke with high
      throughput and high precision.

PMID- 23558297
TI  - Vinclozolin: a case study on the identification of endocrine active substances in
      the past and a future perspective.
AB  - In the late 1980s vinclozolin was tested for prenatal developmental toxicity in
      rats for registration purposes in USA. At 1000mg/kgbw, 95% of all fetuses were
      female upon visual inspection (ano-genital distance determination). Anti
      androgenic effects (AA) were also noted in a subsequent 2-generation study. These
      findings triggered mechanistic investigations at BASF and at US-EPA. Results
      published by the latter were the starting point of the endocrine disruption (ED)
      discussion in the 1990s. AA effects of vinclozolin are mediated by two
      metabolites, which have an antagonistic effect on the androgen receptor.
      Currently, determination of ED has become a major end-point in toxicology testing
      and the US-EPA has set up an elaborated testing paradigm to fulfill this
      requirement. Future screening for ED can be improved making use of new
      technologies. ED modes of action can be determined by three alternative (3R)
      methods. Steroid synthesis in H295R cells (1), androgen-receptor binding in
      modified yeast (2) and metabolomics (3). Using vinclozolin as a case study,
      results indicate: (1) an effect on steroid synthesis in vitro, (2) an
      antagonistic effect on the androgen receptor and (3) that the metabolome profile
      of vinclozolin is similar to that of other receptor mediated anti-androgens (e.g.
      flutamide). 

PMID- 23558296
TI  - ECETOC Florence workshop on risk assessment of endocrine substances, including
      the potency concept.
AB  - The European regulation on plant protection products (1107/2009) and the Biocidal
      Products Regulation (EC Regulation 528/2012) only support the marketing and use
      of chemicals if they do not cause endocrine disruption in humans or wildlife
      species. Also, substances with endocrine properties are subject to authorization
      under the European regulation on the registration, evaluation, authorization and
      restriction of chemicals (REACH; 1907/2006). Therefore, the regulatory
      consequences of identifying a substance as an endocrine disrupting chemical are
      severe. In contrast to that, basic scientific criteria, necessary to define
      endocrine disrupting properties, are not described in any of these legislative
      documents. Thus, the European Center for Ecotoxicology and Toxicology of
      Chemicals (ECETOC) established a task force to provide scientific criteria for
      the identification and assessment of chemicals with endocrine disrupting
      properties that may be used within the context of these three legislative texts
      (ECETOC, 2009a). In 2009, ECETOC introduced a scientific framework as a possible
      concept for identifying endocrine disrupting properties within a regulatory
      context (ECETOC, 2009b; Bars et al., 2011a,b). The proposed scientific criteria
      integrated, in a weight of evidence approach, information from regulatory
      (eco)toxicity studies and mechanistic/screening studies by combining evidence for
      adverse effects detected in apical whole-organism studies with an understanding
      of the mode of action (MoA) of endocrine toxicity. However, since not all
      chemicals with endocrine disrupting properties are of equal hazard, an adequate
      concept should also be able to differentiate between chemicals with endocrine
      properties of low concern from those of higher concern (for regulatory purposes).
      For this purpose, the task force refined this part of their concept. Following an
      investigation of the key factors at a second workshop of invited regulatory,
      academic and industry scientists, the guidance was advanced further. For human
      health assessments it is based on the relevance to humans of the endocrine
      mechanism of toxicity, the specificity of the endocrine effects with respect to
      other toxic effects, the potency of the chemical to induce endocrine toxicity and
      consideration of exposure levels. 

PMID- 23558298
TI  - Upconverting rare-earth nanoparticles with a paramagnetic lanthanide complex
      shell for upconversion fluorescent and magnetic resonance dual-modality imaging.
AB  - Multi-modal imaging based on multifunctional nanoparticles is a promising
      alternative approach to improve the sensitivity of early cancer diagnosis. In
      this study, highly upconverting fluorescence and strong relaxivity rare-earth
      nanoparticles coated with paramagnetic lanthanide complex shells and polyethylene
      glycol (PEGylated UCNPs@DTPA-Gd(3+)) are synthesized as dual-modality imaging
      contrast agents (CAs) for upconverting fluorescent and magnetic resonance dual
      modality imaging. PEGylated UCNPs@DTPA-Gd(3+) with sizes in the range of 32-86 nm
      are colloidally stable. They exhibit higher longitudinal relaxivity and
      transverse relaxivity in water (r1 and r2 values are 7.4 and 27.8 s(-1) per mM
      Gd(3+), respectively) than does commercial Gd-DTPA (r1 and r2 values of 3.7 and
      4.6 s(-1) per mM Gd(3+), respectively). They are found to be biocompatible. In
      vitro cancer cell imaging shows good imaging contrast of PEGylated UCNPs@DTPA
      Gd(3+). In vivo upconversion fluorescent imaging and T1-weighted MRI show
      excellent enhancement of both fluorescent and MR signals in the livers of mice
      administered PEGylated UCNPs@DTPA-Gd(3+). All the experimental results indicate
      that the synthesized PEGylated UCNPs@DTPA-Gd(3+) present great potential for
      biomedical upconversion of fluorescent and magnetic resonance dual-modality
      imaging applications.

PMID- 23558299
TI  - Developmental disruption of gamma-aminobutyric acid function in the medial
      prefrontal cortex by noncontingent cocaine exposure during early adolescence.
AB  - BACKGROUND: Drug experimentation during adolescence is associated with increased
      risk of drug addiction relative to any other age group. To further understand the
      neurobiology underlying such liability, we investigate how early adolescent
      cocaine experience impacts medial prefrontal cortex (mPFC) network function in
      adulthood. METHODS: A noncontingent administration paradigm was used to assess
      the impact of early adolescent cocaine treatment (rats; postnatal days [PD] 35
      40) on the overall inhibitory regulation of mPFC activity in adulthood (PD 65-75)
      by means of histochemical and in vivo electrophysiological measures combined with
      pharmacologic manipulations. RESULTS: Cocaine exposure during early adolescence
      yields a distinctive hypermetabolic prefrontal cortex state that was not observed
      in adult-treated rats (PD 75-80). Local field potential recordings revealed that
      early adolescent cocaine exposure is associated with an attenuation of mPFC gamma
      aminobutyric acid (GABA)ergic inhibition evoked by ventral hippocampal
      stimulation at beta and gamma frequencies that endures throughout adulthood. Such
      cocaine-induced mPFC disinhibition was not observed in adult-exposed animals.
      Furthermore, the normal developmental upregulation of parvalbumin
      immunoreactivity observed in the mPFC from PD 35 to PD 65 is lacking following
      early adolescent cocaine treatment. CONCLUSIONS: Our data indicate that repeated
      cocaine exposure during early adolescence can elicit a state of mPFC
      disinhibition resulting from a functional impairment of the local prefrontal
      GABAergic network that endures through adulthood. A lack of acquisition of
      prefrontal GABAergic function during adolescence could trigger long-term deficits
      in the mPFC that may increase the susceptibility for the onset of substance abuse
      and related psychiatric disorders.

PMID- 23558301
TI  - Persisting in papyrus: size, oxidative stress, and fitness in freshwater
      organisms adapted to sustained hypoxia.
AB  - Aquatic hypoxia is generally viewed as stressful for aerobic organisms. However,
      hypoxia may also benefit organisms by decreasing cellular stress, particularly
      that related to free radicals. Thus, an ideal habitat may have the minimum O2
      necessary to both sustain aerobic metabolism and reduce the need to scavenge free
      radicals and repair free radical damage. The ability of aquatic organisms to
      sustain aerobic metabolism relates in part to the ability to maximize gas
      diffusion, which can be facilitated by small body size when O2 uptake occurs
      across the body surface, by a large gill surface area, or by the ability to use
      atmospheric air. We use water-breathing organisms in chronically hypoxic papyrus
      (Cyperus papyrus) swamps of East Africa to test the hypothesis that cellular
      level benefits of hypoxia may translate into increased fitness, especially for
      small organisms. A review of recent studies of fingernail clams (Sphaerium sp.)
      shows that clams living in sustained hypoxia have minimized oxidative stress and
      that these cellular-level benefits may lead to increased fitness. We suggest that
      organisms in the extreme conditions in the papyrus swamps provide a unique
      opportunity to challenge the conventional classification of hypoxic habitats as
      'stressful' and normoxic habitats as 'optimal.'

PMID- 23558302
TI  - Correlation analysis of the urban heat island effect and the spatial and temporal
      distribution of atmospheric particulates using TM images in Beijing.
AB  - This study combines the methods of observation statistics and remote sensing
      retrieval, using remote sensing information including the urban heat island (UHI)
      intensity index, the normalized difference vegetation index (NDVI), the
      normalized difference water index (NDWI), and the difference vegetation index
      (DVI) to analyze the correlation between the urban heat island effect and the
      spatial and temporal concentration distributions of atmospheric particulates in
      Beijing. The analysis establishes (1) a direct correlation between UHI and DVI;
      (2) an indirect correlation among UHI, NDWI and DVI; and (3) an indirect
      correlation among UHI, NDVI, and DVI. The results proved the existence of three
      correlation types with regional and seasonal effects and revealed an interesting
      correlation between UHI and DVI, that is, if UHI is below 0.1, then DVI increases
      with the increase in UHI, and vice versa. Also, DVI changes more with UHI in the
      two middle zones of Beijing.

PMID- 23558300
TI  - How might circadian rhythms control mood? Let me count the ways...
AB  - Mood disorders are serious diseases that affect a large portion of the
      population. There have been many hypotheses put forth over the years to explain
      the development of major depression, bipolar disorder, and other mood disorders.
      These hypotheses include disruptions in monoamine transmission, hypothalamus
      pituitary-adrenal axis function, immune function, neurogenesis, mitochondrial
      dysfunction, and neuropeptide signaling (to name a few). Nearly all people
      suffering from mood disorders have significant disruptions in circadian rhythms
      and the sleep/wake cycle. In fact, altered sleep patterns are one of the major
      diagnostic criteria for these disorders. Moreover, environmental disruptions to
      circadian rhythms, including shift work, travel across time zones, and irregular
      social schedules, tend to precipitate or exacerbate mood-related episodes. Recent
      studies have found that molecular clocks are found throughout the brain and body
      where they participate in the regulation of most physiological processes,
      including those thought to be involved in mood regulation. This review will
      summarize recent data that implicate the circadian system as a vital regulator of
      a variety of systems that are thought to play a role in the development of mood
      disorders. 

PMID- 23558303
TI  - Fluid management during video-assisted thoracoscopic surgery for lung resection:
      a randomized, controlled trial of effects on urinary output and postoperative
      renal function.
AB  - BACKGROUND: Increased perioperative fluid administration is an independent risk
      factor for lung injury after pulmonary resection. In clinical practice, fluid
      therapy is heavily guided by urinary output; however, diuretic response to plasma
      volume expansion has been reported to be blunted during anesthesia and surgery.
      We therefore hypothesized that in patients undergoing video-assisted
      thoracoscopic surgery, different regimens of intraoperative fluid management
      would not affect urinary output as would be expected in the nonsurgical scenario.
      Moreover, a restrictive perioperative fluid approach, as indicated in these
      operations, will not harm renal function. METHODS: One hundred two patients
      undergoing video-assisted thoracoscopic surgery were randomly allocated to
      receive intraoperatively either high (8 mL/[kg . h]; n = 51) or low (2 mL/[kg .
      h]; n = 51) amounts of Ringer's lactate solution. The primary end point was
      intraoperative urinary output. Secondary end points included postoperative
      creatinine serum levels and postoperative complication rate. RESULTS: Demographic
      and surgical data were comparable between groups. Regardless of the
      intraoperatively fluids administered (mean +/- SD, 2131 +/- 850 vs 1035 +/- 652
      mL in high and low groups, respectively; P < .0001), urinary output was similar
      (median 300 mL). Perioperative creatinine serum levels decreased significantly
      postoperatively and were not significantly different among the groups.
      CONCLUSIONS: In patients undergoing video-assisted thoracoscopic surgery,
      intraoperative urinary output and postoperative renal function are not affected
      by administration of fluids in the range of 2 to 8 mL/(kg . h). The clinical
      practice of administering fluids to enhance diuresis in the perioperative period
      should therefore be abandoned.

PMID- 23558304
TI  - Moderate hypothermia during aortic arch surgery is associated with reduced risk
      of early mortality.
AB  - OBJECTIVE: Selective antegrade cerebral perfusion (ACP) during hypothermic
      circulatory arrest (HCA) provides cerebral protection during aortic arch surgery.
      However, the ideal temperature for HCA during ACP remains unknown. Clinical
      outcomes were compared in patients who underwent moderate (nasopharyngeal
      temperature, >= 20  degrees C) versus deep (nasopharyngeal temperature, <20 
      degrees C) HCA with ACP during aortic arch repair. METHODS: By using a
      prospectively maintained clinical database, we analyzed data from 221 consecutive
      patients who underwent aortic arch replacement with HCA and ACP between December
      2006 and May 2009. Seventy-eight patients underwent deep hypothermia (mean lowest
      temperature, 16.8  degrees C +/- 1.7  degrees C) and 143 patients underwent
      moderate hypothermia (mean, 22.9  degrees C +/- 1.4  degrees C) before systemic
      circulatory arrest was initiated. Multivariate stepwise logistic and linear
      regressions were performed to determine whether depth of hypothermia
      independently predicted postoperative outcomes and blood-product use. RESULTS:
      Compared with moderate hypothermia, deep hypothermia was associated independently
      with a greater risk of in-hospital death (7.7% vs 0.7%; odds ratio [OR], 9.3; 95%
      confidence interval [CI], 1.1-81.6; P = .005) and 30-day all-cause mortality
      (9.0% vs 2.1%; OR, 4.7; 95% CI, 1.2-18.6; P = .02), and with longer
      cardiopulmonary bypass time (154 +/- 62 vs 140 +/- 46 min; P = .008). Deep
      hypothermia also was associated with a higher incidence of stroke, although this
      association was not statistically significant (7.6% vs 2.8%; P = .073; OR, 4.3;
      95% CI, 0.9-12.5). No difference was seen in acute kidney injury, blood product
      transfusion, or need for surgical re-exploration. CONCLUSIONS: Moderate
      hypothermia with ACP is associated with lower in-hospital and 30-day mortality,
      shorter cardiopulmonary bypass time, and fewer neurologic sequelae than deep
      hypothermia in patients who undergo aortic arch surgery with ACP.

PMID- 23558305
TI  - The use of X-ray absorption and synchrotron based micro-X-ray fluorescence
      spectroscopy to investigate anti-cancer metal compounds in vivo and in vitro.
AB  - X-ray absorption spectroscopy (XAS) and micro-synchrotron based X-ray
      fluorescence (micro-SXRF) are element specific spectroscopic techniques and have
      been proven to be valuable tools for the investigation of changes in the chemical
      environment of metal centres. XAS allows the determination of the oxidation
      state, the coordination motif of the probed element, the identity and the number
      of adjacent atoms and the absorber-ligand distances. It is further applicable to
      nearly all types of samples independent of their actual physical state (solid,
      liquid, gaseous) down to MUM concentrations. Micro-SXRF can provide information
      on the distribution and concentration of multiple elements within a sample
      simultaneously, allowing for the chemical state of several elements within
      subcellular compartments to be probed. Modern third generation synchrotrons offer
      the possibility to investigate the majority of the biologically relevant
      elements. The biological mode of action of metal-based compounds often involves
      interactions with target and/or transport molecules. The presence of reducing
      agents may also give rise to changes in the coordination sphere and/or the
      oxidation state. XAS and micro-SXRF are ideal techniques for investigating these
      issues. This tutorial review introduces the use of XAS and micro-SXRF techniques
      into the field of inorganic medicinal chemistry. The results obtained for
      platinum, ruthenium, gallium, gold and cobalt compounds within the last few years
      are presented.

PMID- 23558306
TI  - Stress-induced anhedonia correlates with lower hippocampal serotonin transporter
      protein expression.
AB  - The serotonin transporter (5-HTT) regulates the extracellular concentration of
      serotonin, influencing neurotransmission. Evidence suggests that 5-HTT is altered
      during depression, but the precise changes in 5-HTT expression in the
      pathogenesis and treatment of depression are not clear. We investigated the
      protein expression of hippocampal 5-HTT in CD-1 mice exposed to unpredictable
      chronic mild stress for 10 continuous weeks. Following 6 weeks of the stress
      procedure, the mice were separated into anhedonic and non-anhedonic groups, which
      were then treated with fluoxetine (FLX, 10mg/kg/day, i.p.) for 4 weeks.
      Behavioral state and therapeutic efficacy of the drug treatment were assessed
      using sucrose preference, physical state of the coat and body weight. Our results
      show that changes in hippocampal 5-HTT protein expression correlated with stress
      induced behavioral states. Decreases in 5-HTT expression were associated with the
      stress-induced anhedonic state, whereas increases were associated with the stress
      induced non-anhedonic state. Following FLX treatment, the changes in 5-HTT
      expression were reversed in a subpopulation of anhedonic mice, i.e., the
      treatment-responsive anhedonic mice. The treatment did not alter the changes in
      the treatment-resistant anhedonic mice or in the non-anhedonic mice. The data
      indicate that down-regulation of hippocampal 5-HTT protein expression is a
      signature change associated with anhedonia, a key endophenotype of clinical
      depression. Differential changes in 5-HTT expression may contribute to variations
      in the susceptibility to anhedonia.

PMID- 23558307
TI  - Food-entrained patterns in orexin cells reveal subregion differential activation.
AB  - Rats under a restricted feeding schedule develop food anticipatory activity 2-3h
      prior food access, characterized by increased arousal, foraging and exploratory
      behavior. This anticipatory behavior is not observed when rodents are allowed ad
      libitum food access and reappears for several cycles when food-entrained animals
      are fasted. Previously we reported that food entrainment also produces increased
      expression of c-Fos protein in the dorsomedial nucleus (DMH), in the perifornical
      area (PeF) and in the lateral hypothalamic area (LH) anticipating food intake.
      These hypothalamic structures contain abundant orexin (ORX) producing neurons and
      promote arousal, reward and metabolic balance, thus we explored the participation
      of the orexinergic system in food-entrainment by evaluating in food entrained
      rats (RF) the expression of c-Fos in ORX cells in anticipation, during and after
      food access, and in rats exhibiting persistent activation in fasting after
      interruption of the food-entrainment protocol (RF-Fast). Data were compared with
      ad libitum controls and with a 22-h fasted group. RF rats exhibited a food
      entrained rhythm of c-Fos in ORX cells in the DMH, LH and PeF with highest levels
      at the time of meal delivery and after food ingestion. In RF-Fast rats the food
      entrained pattern of ORX cells persisted in the PeF and LH and partially in the
      DMH, which in addition exhibited an earlier activation. We conclude that ORX
      cells in PeF and LH exhibit self sustained oscillations driven by food
      entrainment, whereas the DMH may mediate arousal mechanisms that elicit
      anticipatory activity.

PMID- 23558309
TI  - Multiparametric body composition analysis and anthropometric empirical indicator:
      obesity based south Indian perspective.
AB  - BACKGROUND: Obesity has emerged to be a global threat to mankind. Many
      abnormalities such as cardiovascular diseases and diabetes emerge as outcomes of
      obesity. OBJECTIVES: The present study aimed at bringing out a technique which
      considers the combinational measurement of all essential anthropometric
      circumferences and body mass index (BMI), so that the accurate assessment of
      obesity can be made. To date, BMI has been considered to be the main adiposity
      index, but the distribution of body fat was not taken into account by BMI. The
      contradictory outcomes by BMI pertaining to risk factor detection in various
      ethnicities and populations were witnessed. Also, BMI failed to gauge obesity in
      muscular body builders who possess small waists and large torsos. MATERIALS AND
      METHODS: The study adopted a cross-sectional design and 107 subjects from urban
      south India participated. The measurements of body composition and anthropometry
      were shown. RESULTS: The higher significant difference of <= 0.001 was observed
      in male and female studied population, when AEI (BIA1), AEI (EXTERNAL) and BMI
      were compared against BFM (measured by both the devices BIA1 and BIA2).
      CONCLUSIONS: The results exhibited the prominence of AEI (Anthropometric
      Empirical Indicator, which is the combinational measurement of all essential
      anthropometric circumferences and BMI) over BMI. Also, the validity of the
      effective functioning of low-cost, portable, simple protocol based body
      composition analyzer on par with the highercost, standard body composition
      analyzer was demonstrated by the present study.

PMID- 23558308
TI  - Contribution of olivofloccular circuitry developmental defects to atypical gaze
      in autism.
AB  - Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit,
      altered movement perception and deficits in facial perception. The olivofloccular
      neuronal circuit is a major contributor to eye movement control. This study of
      the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes
      in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects
      of the oculomotor system, including avoidance of eye contact and poor or no eye
      contact, were reported in 88% of autistic subjects with postmortem-detected
      floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with
      deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs);
      deficit and abnormalities of granule, basket, stellate and unipolar brush cells;
      and structural defects and abnormal orientation of Bergmann glia are indicators
      of profound disruption of flocculus circuitry in a dysplastic area. The average
      volume of PCs was 26% less in the dysplastic region than in the unaffected region
      of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of
      PCs in the entire cerebellum was 25% less in the autistic subjects than in the
      control subjects (p<0.001). Findings from this study and a parallel study of the
      inferior olive (IO) suggest that focal floccular dysplasia combined with IO
      neurons and PC developmental defects may contribute to oculomotor system
      dysfunction and atypical gaze in autistic subjects.

PMID- 23558310
TI  - Complete metabolic response in a patient with repeatedly relapsed non-small cell
      lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib.
AB  - A 55-year-old Caucasian woman with lung adenocarcinoma stage IV presented with
      repeated relapse after treatment with cytotoxic chemotherapy (carboplatin,
      gemcitabine, docetaxel, pemetrexed) and targeted agents (erlotinib, cetuximab,
      sunitinib). Comprehensive molecular diagnostics (EGFR-, ALK-, RAS-, BRAF-, PIK3CA
      , HER2- and DDR2-aberrations) were performed and failed initially to detect any
      driver mutation. While the patient suffered from rapid deterioration of her
      general condition, in particular from progressive dyspnea due to lung metastases,
      we implemented screening for RET- and ROS1 translocations into our molecular
      diagnostic program based on recent reports of these new molecular subgroups in
      lung adenocarcinoma. On retesting the patient's tumor sample was found to harbor
      a ROS1-translocation. The patient was subsequently treated with crizotinib and
      experienced a pronounced clinical improvement corresponding to a complete
      metabolic response in (18)F-FDG-PET and a good and confirmed partial response in
      CT (RECIST 1.1). Our case exemplifies the need for rapid implementation of newly
      discovered rare genetic lung cancer subtypes in routine molecular diagnostics.

PMID- 23558312
TI  - Selective terminal function modification of SAMs driven by low-energy electrons
      (0-15 eV).
AB  - Low-energy electron induced degradation of a model self-assembled monolayer (SAM)
      of acid terminated alkanethiol was studied under ultra-high vacuum (UHV)
      conditions at room and low (~40 K) temperatures. Low-energy electron induced
      chemical modifications of 11-mercaptoundecanoic acid (MUA, HS-(CH2)10-COOH) SAMs
      deposited on gold were probed in situ as a function of the irradiation energy
      (<11 eV) by combining two complementary techniques: High Resolution Electron
      Energy Loss Spectroscopy (HREELS), a surface sensitive vibrational spectroscopy
      technique, and Electron Stimulated Desorption (ESD) analysis of neutral
      fragments. The SAM's terminal functions were observed to be selectively damaged
      at around 1 eV by a resonant electron attachment mechanism, observed to decay by
      CO, CO2 and H2O formation and desorption. CO2 and H2O were also directly
      identified at low temperature by vibrational analysis of the irradiated SAMs. At
      higher irradiation energy, both terminal functions and spacer alkyl chains are
      damaged upon electron irradiation, by resonant and non-resonant processes.

PMID- 23558311
TI  - Perioperative considerations of bilateral total knee replacement: a review.
AB  - Bilateral total knee replacement is becoming one of the more commonly performed
      orthopedic procedures for patients with advanced arthritis of both knees. The
      surgeon may decide to operate on both knees simultaneously, sequentially, or in a
      staged manner. The safety of this procedure is still debated due to wide
      variation in the studies and their endpoints. Although there are advantages with
      bilateral procedures such as reduced cost and improved rehabilitation, there is
      definite evidence of increased cardiopulmonary, thromboembolic, neurological,
      bleeding, and transfusion complications with bilateral knee replacement versus
      unilateral knee replacement, particularly in elderly patients with comorbidities.

PMID- 23558313
TI  - Prediction of oral disintegration time of fast disintegrating tablets using
      texture analyzer and computational optimization.
AB  - One of the promising approaches to predict in vivo disintegration time of orally
      disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the
      method is able to provide good in vitro in vivo correlation (IVIVC) in the case
      of different tablets, it might be able to predict the oral disintegration time of
      similar products. However, there are many tablet parameters that influence the in
      vivo and the in vitro disintegration time of ODT products. Therefore, the
      measured in vitro and in vivo disintegration times can occasionally differ, even
      if they coincide in most cases of the investigated products and the in vivo
      disintegration times may also change if the aimed patient group is suffering from
      a special illness. If the method is no longer able to provide good IVIVC, then
      the modification of a single instrumental parameter may not be successful and the
      in vitro method must be re-set in a complex manner in order to provide
      satisfactory results. In the present experiment, an optimization process was
      developed based on texture analysis measurements using five different tablets in
      order to predict their in vivo disintegration times, and the optimized texture
      analysis method was evaluated using independent tablets.

PMID- 23558314
TI  - Proof of concept studies to confirm the delivery of curcumin loaded solid lipid
      nanoparticles (C-SLNs) to brain.
AB  - Having achieved a significant bioavailability of curcumin by its incorporation
      into SLNs (C-SLNs) during pharmacokinetic (32-155 times) and pharmacodynamic (3-4
      times) studies, our intent was to proof their targeting to brain. Hence,
      fluorescent/confocal microscopy, biodistribution and gamma scintigraphy
      techniques were explored to observe the presence of C-SLNs in the brain. 1h post
      p.o administration of C-SLNs/free curcumin (C-S) to rats, blood was withdrawn,
      following which the animals were sacrificed and their harvested brains were
      frozen at -80 degrees C. The obtained plasma and brain cryosections were observed
      for fluorescence under fluorescent/confocal microscope. Biodistribution study was
      performed using (99m)Tc-labeled C-SLNs and C-S in Balb/c mice after p.o. and i.v.
      administration and % radioactivity/g organ was recorded. Subsequent to this gamma
      scintigraphs of the New Zealand rabbits following similar treatments were
      performed. Presence of yellow fluorescent particles in plasma and brain indicated
      effective delivery of C-SLNs across the gut wall and the BBB. (Blood)AUCoral
      value for C-SLNs was 8.135 times greater than that for C-S, confirming a
      prolonged circulation of former. The ratio of blood AUCi.v. C-SLN/C-S in blood is
      <=1 while the ratio in brain promisingly indicates 30 times higher preferential
      distribution of C-SLNs into brain confirming their direct delivery.

PMID- 23558315
TI  - Active drug targeting: lessons learned and new things to consider.
AB  - There is "hype" surrounding passive and active drug targeting of diseased tissues
      in vivo. The most common example of passive targeting is the utilisation of the
      "enhanced permeation and retention" phenomenon to target solid tumours and
      inflamed tissues. Alternatively, targeting moieties or "ligands" could be
      conjugated to the delivery system offering "actively" targeted delivery systems.
      The targets are usually receptors that are up-regulated in the biological areas
      of interest. Targeted drug delivery has been proposed to treat many diseases,
      such as cardiovascular diseases and diabetes. However, the most important
      application of targeted drug delivery is to treat cancerous tumours.
      Standardisation of in vitro and in vivo assays currently in place to assess the
      targeting efficiency of such systems is of utmost importance since heterogeneity
      in targeting assays and target validation could easily bias conclusions made
      affecting the future perspective of the field of active drug targeting. 

PMID- 23558316
TI  - Computational approach for designing tumor homing peptides.
AB  - Tumor homing peptides are small peptides that home specifically to tumor and
      tumor associated microenvironment i.e. tumor vasculature, after systemic
      delivery. Keeping in mind the huge therapeutic importance of these peptides, we
      have made an attempt to analyze and predict tumor homing peptides. It was
      observed that certain types of residues are preferred in tumor homing peptides.
      Therefore, we developed support vector machine based models for predicting tumor
      homing peptides using amino acid composition and binary profiles of peptides.
      Amino acid composition, dipeptide composition and binary profile-based models
      achieved a maximum accuracy of 86.56%, 82.03%, and 84.19% respectively. These
      methods have been implemented in a user-friendly web server, TumorHPD. We
      anticipate that this method will be helpful to design novel tumor homing
      peptides. TumorHPD web server is freely accessible at
      http://crdd.osdd.net/raghava/tumorhpd/.

PMID- 23558317
TI  - Morbidity and mortality of pneumonia in adults in six Latin American countries.
AB  - OBJECTIVE: To estimate the morbidity and mortality of pneumonia in adults over 50
      years of age in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela.
      METHODS: Local data sources were queried to estimate the number of hospitalized
      and outpatient pneumonia cases and deaths in the year 2009. Pneumonia cases were
      identified in adults aged >=50 years using ICD-10 codes. The hospital case
      fatality rate (HCFR) by age corresponds to the percentage of mortality per
      hospitalization. RESULTS: Cases of hospitalized pneumonia (incidence per 100 000
      inhabitants/year) in adults >=50 years were: Argentina 39 674 (401.1); Brazil 225
      341 (611.6); Chile 30 434 (738.5); Colombia 26 955 (326.6); Mexico 82 397
      (413.1); Venezuela 31 601 (640.1). The number of hospital deaths (CFR%) were:
      Argentina 5099 (13%); Brazil 47 287 (21%); Chile 3072 (10%); Colombia 2981 (11%);
      Mexico 13 312 (16%); Venezuela 11 101 (35%). Cases of outpatient pneumonia
      (incidence per 100 000 inhabitants/year) were: Argentina 54 093 (546.8); Brazil
      260 277 (706.4); Chile 33 173 (804.9); Colombia 27 713 (335.8); Mexico 83 354
      (417.9); Venezuela 39 645 (803.0). The percentage of episodes treated as
      outpatient was 64% (range 57-80%) among those aged 50-64 years and 39% (range 8
      56%) among those >=85 years. Across countries, 51% of hospitalizations (range 42
      63%) and 69% of deaths (range 65-72%) were in adults >=75 years. CONCLUSIONS:
      Pneumonia is a common cause of hospitalization and mortality in adults in Latin
      America. Incidence increases substantially with increasing age, as does the
      likelihood of hospitalization and mortality.

PMID- 23558318
TI  - Outbreak of Serratia marcescens postsurgical bloodstream infection due to
      contaminated intravenous pain control fluids.
AB  - BACKGROUND: Serratia marcescens is an important nosocomial pathogen causing
      significant outbreaks. Here we report an outbreak of bloodstream infection caused
      by S. marcescens at a 3500-bed hospital in Taiwan. The effective cooperative
      efforts of both laboratory personnel and infection control practitioners (ICPs)
      jointly contributed to the total control of the outbreak. METHODS: A sudden
      increase in the isolation of S. marcescens from blood cultures was noted in the
      Clinical Microbiology Laboratory. The information was passed to the ICPs and an
      investigation was initiated. Pulsed-field gel electrophoresis was used to study
      the relationships among the isolates. RESULTS: Pulsotype A was identified in 43
      (82.7%) of the 52 blood isolates studied. They were isolated from 52 patients
      distributed across 22 wards that were surveyed by seven ICPs. All patients had
      undergone surgery before the infection, and fentanyl-containing intravenous
      fluids were used for pain control in 43 of them. Isolates from 42 belonged to
      pulsotype A. Three S. marcescens isolates, all from fentanyl-containing fluids
      and demonstrating pulsotype A, were identified from 251 environmental cultures.
      All fentanyl-containing fluids that were in use were withdrawn and the outbreak
      was stopped. CONCLUSIONS: The outbreak of S. marcescens bloodstream infection
      apparently occurred through the use of fentanyl-containing fluids contaminated by
      a pulsotype A S. marcescens.

PMID- 23558319
TI  - Efficient quantum dot light-emitting diodes with solution-processable molybdenum
      oxide as the anode buffer layer.
AB  - Quantum dot light-emitting diodes (QD-LEDs) are characterized by pure and
      saturated emission colors with narrow bandwidth. Optimization of the device
      interface is an effective way to achieve stable and high-performance QD-LEDs.
      Here we utilized solution-processed molybdenum oxide (MoOx) as the anode buffer
      layer on ITO to build efficient QD-LEDs. Using MoOx as the anode buffer layer
      provides the QD-LED with good Ohmic contact and a small charge transfer
      resistance. The device luminance is nearly independent of the thickness of the
      MoOx anode buffer layer. The QD-LEDs with a MoOx anode buffer layer exhibit a
      maximum luminance and luminous efficiency of 5230 cd m(-2) and 0.67 cd A(-1) for
      the yellow emission at 580 nm, and 7842 cd m(-2) and 1.49 cd A(-1) for the red
      emission at 610 nm, respectively.

PMID- 23558320
TI  - Early trends for invasive pneumococcal infections in children after the
      introduction of the 13-valent pneumococcal conjugate vaccine.
AB  - BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced
      for routine administration to infants and children in 2010 in the United States.
      We have monitored clinical and microbiologic features of invasive pneumococcal
      infections among children before and after PCV13 use. METHODS: Infants and
      children cared for at 8 children hospitals in the United States with culture
      proven invasive infections caused by S. pneumoniae were identified in an ongoing
      prospective surveillance study. Demographic and clinical data were recorded on a
      standard case report form. Serotype and antimicrobial susceptibilities of
      isolates were determined. RESULTS: Since routine PCV13 immunization in 2010,
      invasive pneumococcal infections decreased 42% overall and 53% for children <24
      months of age in 2011 compared with the average number of cases for 2007 to 2009.
      PCV13 serotype isolates decreased 57% during these same time periods; 19A, 7F and
      3 decreased by 58%, 54% and 68%, respectively. The number of infections caused by
      serotypes 1 and 6C also decreased in 2011. The most common non-PCV13 serotypes
      encountered in 2010 and 2011 combined were 33F, 22F, 12, 15B, 15C, 23A and 11.
      Bacteremia, pneumonia and mastoiditis cases decreased more than meningitis cases.
      CONCLUSIONS: After the introduction of PCV13, invasive pneumococcal infections
      decreased among 8 children hospitals compared with the 3 years before PCV13 use.
      Slight increases in some non-PCV13 serotype isolates were noted in 2011.
      Continued surveillance is necessary to determine the effectiveness of PCV13
      including herd protection as well as any emerging invasive serotypes.

PMID- 23558321
TI  - Relationships between rhinitis symptoms, respiratory viral infections and
      nasopharyngeal colonization with Streptococcus pneumoniae, Haemophilus influenzae
      and Staphylococcus aureus in children attending daycare.
AB  - BACKGROUND: Nasal bacterial colonization is often dubbed "asymptomatic." We
      hypothesized that rhinitis, common in preschool children, is associated with
      bacterial colonization and that respiratory viruses, which cause rhinitis,
      interact with bacteria in ways which promote transmission. METHODS: Five hundred
      eighty-five children (4.2-73.6 months) attending daycare had clinical
      information, a rhinitis score and nasal swabs collected in February 2009. Swabs
      in soya tryptone glucose glycerine broth were cultured for Streptococcus
      pneumoniae (Sp), Haemophilus influenzae (Hi) and Staphylococcus aureus and
      analyzed by real-time polymerase chain reaction for respiratory viruses, both
      semiquantitatively. RESULTS: Rhinitis symptoms, carriage of Sp and Hi and viral
      detection fell, whereas S. aureus carriage rates rose with age. Significant, age
      independent associations between rhinitis symptoms and detection of Hi (P <
      0.033) and Hi colonization density (P < 0.027) were observed. Of the 42% with
      detected viruses, most (78%) had picornavirus detection. There was a significant
      age-independent association between viral detection (and viral load, picornavirus
      detection and picorn aviral load) and detection of Sp (P = 0.020, 0.035, 0.005,
      0.014) and between viral detection and viral load and Sp colonization density (P
      = 0.024, 0.028) [corrected]. CONCLUSIONS: Hi may promote its own transmission by
      inducing or ampli!fying rhinitis in children. There isa close quantitative
      relationship between respiratory viral detection, including picornavirus
      detection and Spcoloni!zation. These findings have implications for understanding
      disease patho!genesis and formulating prevention strategies using vaccines
      [corrected].

PMID- 23558322
TI  - PCV13 impact evaluations: the obvious and the unpredicted.

PMID- 23558323
TI  - Infections in children treated with biological agents.

PMID- 23558324
TI  - Neutrophil volume, conductivity and scatter in neonatal sepsis.

PMID- 23558325
TI  - Blastomycosis presenting as isolated otitis and otomastoiditis.

PMID- 23558326
TI  - Species-specific PCR improves detection of bacterial pathogens in parapneumonic
      empyema compared with 16S PCR and culture.

PMID- 23558327
TI  - Polio-can it be eradicated from Pakistan?

PMID- 23558328
TI  - Commentary: polio-can it be eradicated from pakistan?

PMID- 23558329
TI  - The Pediatric Infectious Disease Journal(r) newsletter.

PMID- 23558330
TI  - The utility of ultrasound in detecting anterior compartment thickness changes in
      chronic exertional compartment syndrome: a pilot study.
AB  - OBJECTIVE: To test the hypothesis that patients with chronic exertional
      compartment syndrome (CECS) of the anterior leg compartment have an increased
      anterior compartment thickness (ACT) compared with control subjects after
      exertion using ultrasound. DESIGN: Prospective comparison study. SETTING:
      Diagnostic imaging department of a tertiary care hospital. PATIENTS: Four
      patients with CECS and 9 control subjects. INTERVENTIONS: Patients with CECS and
      control subjects ran on a treadmill for up to 10 minutes. Anterior compartment
      thickness (both groups) and anterior compartment pressure (CECS patients) were
      measured before exertion and at scheduled intervals after exertion. MAIN OUTCOME
      MEASURES: Anterior compartment thickness, percentage change in ACT from rest, and
      compartment pressure. RESULTS: Anterior compartment pressures were diagnostic of
      CECS using the modified Pedowitz criteria in patients with CECS. Mean percentage
      change in ACT from rest in patients with CECS versus control subjects at 0.5
      minutes was 21.3% versus 6.32% [95% confidence interval (CI), 6.92-35.6 and 0.094
      12.5, respectively; P = 0.011]; at 2.5 minutes, it was 24.6% versus 4.22% (95%
      CI, 10.7-38.5 and -1.85-10.3, respectively; P = 0.003); and at 4.5 minutes, it
      was 24.9% versus 5.08% (95% CI, 14.3-35.5 and -0.813-11.0, respectively; P =
      0.003). Mean ACT in patients with CECS versus control subjects significantly
      increased after exertion (P = 0.003) at 0.5 minutes, 2.5 minutes, and 4.5
      minutes. CONCLUSIONS: Ultrasonography reveals a significant increase in ACT in
      patients with CECS of the anterior leg compartment. Further studies are warranted
      to validate these findings with the goal of developing anterior leg compartment
      CECS ultrasound diagnostic criteria and exploring the role of using ultrasound to
      diagnose CECS in other compartments.

PMID- 23558331
TI  - Balance error scoring system performance changes after a competitive athletic
      season.
AB  - OBJECTIVE: To evaluate the change in Balance Error Scoring System (BESS)
      performance after an athletic season. DESIGN: A prospective longitudinal group
      study. SETTING: University biomechanics research laboratory. PARTICIPANTS: A
      total of 58 college-aged females (23 soccer student-athletes, 16 volleyball
      student-athletes, and 19 recreationally active healthy college students)
      participated in the study. INTERVENTIONS: The BESS test was administered on 2
      occasions 90 days apart. For the student-athletes, the first test (PRE) was
      administered before the start of their athletic season and the second test (POST)
      was administered immediately after the season. For the recreationally active
      college students, the PRE test was at the beginning of the academic semester and
      the POST test exactly 90 days thereafter. MAIN OUTCOME MEASURES: Total BESS score
      at PRE and POST was compared with a 3 * 2 repeated measures analysis of variance.
      The overall change score and absolute value change score were also calculated and
      compared with a 1-sample t test to an expected change of zero errors. RESULTS:
      There was no group by time interaction; however, there was a main effect for
      time. There was a significant improvement (P = 0.003) between PRE (9.00 +/- 2.97
      errors) and POST (7.92 +/- 2.78 errors) BESS performance. There were significant
      differences for both the overall change score (1.08 errors) and the absolute
      value change score (2.00 errors). CONCLUSIONS: A clinically and statistically
      significant difference in BESS performance was identified after a 90-day
      intercollegiate athletic season.

PMID- 23558332
TI  - Markers of hydration status in a 3-day trail running event.
AB  - OBJECTIVE: To examine the relationships between changes in static prestage and
      poststage measures of commonly used hematological and urinary markers of
      hydration status and body mass (BM) in participants in a 3-day trail run. DESIGN:
      Descriptive field study. SETTING: Three Cranes Challenge trail run, South Africa.
      PARTICIPANTS: Twenty (6 men and 14 women) amateur runners. INTERVENTIONS: In
      stage 1 (S1), 29.3 km and 37.9 km in stage 2 (S2), and 27.8 km in stage 3 (S3).
      MAIN OUTCOME MEASURES: Prestage and poststage individual changes in serum
      osmolality (S osm), serum sodium (s[Na]), plasma volume (PV), urine osmolality (U
      osm), urine specific gravity (U sg), and BM. RESULTS: Consistently, mild
      environmental conditions were experienced on the 3 days of the race (ambient
      temperature range, 11.5-22.8 degrees C). Mean S osm increased by 5 +/- 6, 7 +/-
      9, and 3 +/- 4 mOsm/kg during S1, S2, and S3, respectively, and returned to
      baseline pre-S2 and pre-S3. The correlation between individual prestage and
      poststage changes in S osm, Uosm, and U sg (n = 60) were nonsignificant (P >
      0.05; r = 0.0047, r = 0.0074). There was a significant, but relatively low
      correlation between changes in S osm and percentage reduction in BM (r = 0.35; P
      < 0.01) and prechange and postchange in s[Na] (r = 0.45; P < 0.001). CONCLUSIONS:
      Serum osmality values confirm appropriate interstage rehydration. Changes in U
      osm, U sg, BM, s[Na+], and PV are not closely related to changes in S osm as
      markers of hydration assessment in multiday events in which single static
      measures of hydration status are required. These measures of hydration station
      status are therefore not recommended in this field setting.

PMID- 23558333
TI  - The effect of a comprehensive injury audit program on injury incidence in ballet:
      a 3-year prospective study.
AB  - OBJECTIVE: The aim of this study was to determine whether an intervention with
      individualized conditioning program based on injury history and functional
      movement screening would be effective in reducing ballet injury incidence.
      DESIGN: Prospective 3-year epidemiological study. SETTING: Professional ballet
      company and its in-house medical facility. PARTICIPANTS: Dancers from a
      professional ballet company over the 3-year study period. Participant numbers
      ranged from 52 to 58 (year 1: 52; year 2: 58; year 3: 53). INTERVENTIONS: The
      intervention consisted of individual conditioning programs developed using injury
      history and functional movement screening. Analysis was undertaken of the all
      dancers who were present in the company during the study period. The significance
      of change in injuries over a 3-year period was determined using a Poisson
      distribution model. MAIN OUTCOMES MEASURES: To determine whether individual
      conditioning programs resulted in a decrease in injury incidence over the study
      period. RESULTS: The injury count reduced significantly in years 2 and 3 (P <
      0.001). Injury incidence for male dancers declined from year 1 (in year/1000 h)
      (4.76/1000 h) to year 2 (2.40/1000 h) and year 3 (2.22/1000 h). For women, a
      reduction in the injury incidence was observed from year 1 (4.14/1000 h) to year
      2 (1.71/1000 h) and year 3 (1.81/1000 h). CONCLUSIONS: Through prospective injury
      surveillance, we were able to demonstrate the benefit of individualized
      conditioning programs based on injury history and functional movement screening
      in reducing injuries in ballet. CLINICAL RELEVANCE: The implementation of well
      structured injury surveillance programs can impact on injury incidence through
      its influence on intervention programs.

PMID- 23558334
TI  - Sample entropy and regularity dimension in complexity analysis of cortical
      surface structure in early Alzheimer's disease and aging.
AB  - We apply for the first time the sample entropy (SampEn) and regularity dimension
      model for measuring signal complexity to quantify the structural complexity of
      the brain on MRI. The concept of the regularity dimension is based on the theory
      of chaos for studying nonlinear dynamical systems, where power laws and entropy
      measure are adopted to develop the regularity dimension for modeling a
      mathematical relationship between the frequencies with which information about
      signal regularity changes in various scales. The sample entropy and regularity
      dimension of MRI-based brain structural complexity are computed for early
      Alzheimer's disease (AD) elder adults and age and gender-matched non-demented
      controls, as well as for a wide range of ages from young people to elder adults.
      A significantly higher global cortical structure complexity is detected in AD
      individuals (p<0.001). The increase of SampEn and the regularity dimension are
      also found to be accompanied with aging which might indicate an age-related
      exacerbation of cortical structural irregularity. The provided model can be
      potentially used as an imaging bio-marker for early prediction of AD and age
      related cognitive decline.

PMID- 23558335
TI  - Registration of challenging pre-clinical brain images.
AB  - The size and complexity of brain imaging studies in pre-clinical populations are
      increasing, and automated image analysis pipelines are urgently required. Pre
      clinical populations can be subjected to controlled interventions (e.g., targeted
      lesions), which significantly change the appearance of the brain obtained by
      imaging. Existing systems for registration (the systematic alignment of scans
      into a consistent anatomical coordinate system), which assume image similarity to
      a reference scan, may fail when applied to these images. However, affine
      registration is a particularly vital pre-processing step for subsequent image
      analysis which is assumed to be an effective procedure in recent literature
      describing sophisticated techniques such as manifold learning. Therefore, in this
      paper, we present an affine registration solution that uses a graphical model of
      a population to decompose difficult pairwise registrations into a composition of
      steps using other members of the population. We developed this methodology in the
      context of a pre-clinical model of stroke in which large, variable hyper-intense
      lesions significantly impact registration performance. We tested this technique
      systematically in a simulated human population of brain tumour images before
      applying it to pre-clinical models of Parkinson's disease and stroke.

PMID- 23558336
TI  - A multidimensional approach to an in-depth proteomics analysis of transcriptional
      regulators in neuroblastoma cells.
AB  - The dynamic regulation of transcriptional events is fundamental to many aspects
      of neuronal cell functions. However, proteomics methods have not been routinely
      used in global neuroproteomics analyses of transcriptional regulators because
      they are much less abundant than the "house-keeping" proteins in cells and
      tissues. Recent improvements in both biochemical preparations of nuclear proteins
      and detection sensitivities of proteomics technologies have made the global
      analysis of nuclear transcriptional regulators possible. We report here an
      optimised neuroproteomic method for the analysis of transcriptional regulators in
      the nuclear extracts of SHSY-5Y neuroblastoma cells by combining an improved
      nuclear protein extraction procedure with multidimensional peptide separation
      approaches. We found that rigorous removal of cytoplasmic proteins and
      solubilisation of DNA-associated proteins improved the number of nuclear proteins
      identified. Furthermore, we discovered that multidimensional peptide separations
      by either strong cation exchange (SCX) chromatography or electrostatic repulsion
      hydrophilic interaction chromatography (ERLIC) analysis detected more than 1800
      nuclear proteins, which constitutes one of the largest datasets of nuclear
      proteins reported for a neuronal cell. Thus, in-depth analysis of transcriptional
      regulators for studying neurological diseases are increasingly feasible.

PMID- 23558337
TI  - Ventral striatum activity in response to reward: differences between bipolar I
      and II disorders.
AB  - OBJECTIVE: Little is known about the neurobiology of bipolar II disorder. While
      bipolar I disorder is associated with abnormally elevated activity in response to
      reward in the ventral striatum, a key component of reward circuitry, no studies
      have compared reward circuitry function in bipolar I and bipolar II disorders.
      Furthermore, associations among reward circuitry activity, reward sensitivity,
      and striatal volume remain underexplored in bipolar and healthy individuals. The
      authors examined reward activity in the ventral striatum in participants with
      bipolar I and II disorders and healthy individuals, the relationships between
      ventral striatal activity and reward sensitivity across all participants, and
      between-group differences in striatal gray matter volume and relationships with
      ventral striatal activity across all participants. METHOD: Twenty healthy
      comparison subjects and 32 euthymic bipolar I (N=17) and bipolar II (N=15)
      patients underwent a neuroimaging reward paradigm during functional MRI scanning,
      structural scanning, and completed psychometric and clinical assessments.
      RESULTS: Region-of-interest analyses revealed significant ventral striatal
      activity in all participants during reward anticipation that was significantly
      greater in bipolar II patients compared with the other groups. Ventral striatal
      activity during reward anticipation correlated positively with reward sensitivity
      and fun seeking across all participants. Bipolar II patients had significantly
      greater left putamen volume than bipolar I patients, and left putamen volume
      correlated positively with left ventral striatal activity to reward anticipation
      in all participants. CONCLUSIONS: Abnormally elevated ventral striatal activity
      during reward anticipation may be a potential biomarker of bipolar II disorder.
      These findings highlight the importance of adopting a dimensional approach in the
      study of neural mechanisms supporting key pathophysiological processes that may
      cut across psychiatric disorders.

PMID- 23558338
TI  - Inhibition of biomaterial-induced complement activation attenuates the
      inflammatory host response to implantation.
AB  - Although complement is a known contributor to biomaterial-induced complications,
      pathological implications and therapeutic options remain to be explored. Here we
      investigated the involvement of complement in the inflammatory response to
      polypropylene meshes commonly used for hernia repair. In vitro assays revealed
      deposition of complement activation fragments on the mesh after incubation in
      plasma. Moreover, significant mesh-induced complement and granulocyte activation
      was observed in plasma and leukocyte preparations, respectively. Pretreatment of
      plasma with the complement inhibitor compstatin reduced opsonization >2-fold, and
      compstatin and a C5a receptor antagonist (C5aRa) impaired granulocyte activation
      by 50 and 67%, respectively. We established a clinically relevant mouse model of
      implantation and could confirm deposition of C3 activation fragments on mesh
      implants in vivo using immunofluorescence. In meshes extracted after subcutaneous
      or peritoneal implantation, the amount of immune cell infiltrate in mice
      deficient in key complement components (C3, C5aR), or treated with C5aRa, was
      approximately half of that observed in wild-type littermates or mice treated with
      inactive C5aRa, respectively. Our data suggest that implantation of a widely used
      surgical mesh triggers the formation of an inflammatory cell microenvironment at
      the implant site through complement activation, and indicates a path for the
      therapeutic modulation of implant-related complications.

PMID- 23558340
TI  - Zipfian frequency distributions facilitate word segmentation in context.
AB  - Word frequencies in natural language follow a highly skewed Zipfian distribution,
      but the consequences of this distribution for language acquisition are only
      beginning to be understood. Typically, learning experiments that are meant to
      simulate language acquisition use uniform word frequency distributions. We
      examine the effects of Zipfian distributions using two artificial language
      paradigms-a standard forced-choice task and a new orthographic segmentation task
      in which participants click on the boundaries between words in contexts. Our data
      show that learners can identify word forms robustly across widely varying
      frequency distributions. In addition, although performance in recognizing
      individual words is predicted best by their frequency, a Zipfian distribution
      facilitates word segmentation in context: the presence of high-frequency words
      creates more chances for learners to apply their knowledge in processing new
      sentences. We find that computational models that implement "chunking" are more
      effective than "transition finding" models at reproducing this pattern of
      performance.

PMID- 23558339
TI  - Regulation of ENaC in mice lacking renal insulin receptors in the collecting
      duct.
AB  - The epithelial sodium channel (ENaC) is one of the central effectors involved in
      regulation of salt and water homeostasis in the kidney. To study mechanisms of
      ENaC regulation, we generated knockout mice lacking the insulin receptor (InsR
      KO) specifically in the collecting duct principal cells. Single-channel analysis
      in freshly isolated split-open tubules demonstrated that the InsR-KO mice have
      significantly lower ENaC activity compared to their wild-type (C57BL/6J)
      littermates when animals were fed either normal or sodium-deficient diets.
      Immunohistochemical and Western blot assays demonstrated no significant changes
      in expression of ENaC subunits in InsR-KO mice compared to wild-type littermates.
      Insulin treatment caused greater ENaC activity in split-open tubules isolated
      from wild-type mice but did not have this effect in the InsR-KO mice. Thus, these
      results suggest that insulin increases ENaC activity via its own receptor
      affecting the channel open probability. To further determine the mechanism of the
      action of insulin on ENaC, we used mouse mpkCCDc14 principal cells. Insulin
      significantly augmented amiloride-sensitive transepithelial flux in these cells.
      Pretreatment of the mpkCCDc14 cells with phosphatidylinositol 3-kinase (LY294002;
      10 MUM) or mTOR (PP242; 100 nM) inhibitors precluded this effect. This study
      provides new information about the importance of insulin receptors expressed in
      collecting duct principal cells for ENaC activity.

PMID- 23558342
TI  - The experiences of patients with ascites secondary to cancer: a qualitative
      study.
AB  - BACKGROUND: Ascites secondary to cancer has a dramatic effect on all aspects of
      patients' lives. Healthcare professional surveys have shown that there is
      considerable variation in the management of ascites. AIM: To explore patients'
      experiences of living with ascites and its management. DESIGN: Qualitative
      research study using digitally recorded semi-structured interviews.
      SETTING/PARTICIPANTS: Twelve adult patients with ascites who, between them, had
      undergone 47 paracentesis procedures in hospitals and/or specialist palliative
      care units in Southern England. RESULTS: Symptoms were pain, discomfort and
      effects on appetite, digestion, breathing and mobility. All participants had
      experienced paracentesis in hospital or a specialist palliative care unit, and
      these experiences differed. They had views on what constituted a good procedure:
      setting, competence and pain control. They reported rapid improvement of symptoms
      after paracentesis. While some did not like the idea of a semi-permanent drain,
      those with them appreciated the convenience and not having to wait for repeated
      admissions or the recurrence of symptoms. The interval between ascitic taps was
      seen as a useful guide as to when a semi-permanent drain should be offered.
      Participants had mixed views on participation in a hypothetical randomised
      controlled trial of repeated ascitic taps versus semi-permanent drains.
      CONCLUSION: Patients' experiences of ascites management are variable and could be
      improved. These experiences can inform healthcare professionals. They have views
      on when semi-permanent drains should be offered and future research.

PMID- 23558341
TI  - The branch-site test of positive selection is surprisingly robust but lacks power
      under synonymous substitution saturation and variation in GC.
AB  - Positive selection is widely estimated from protein coding sequence alignments by
      the nonsynonymous-to-synonymous ratio omega. Increasingly elaborate codon models
      are used in a likelihood framework for this estimation. Although there is
      widespread concern about the robustness of the estimation of the omega ratio,
      more efforts are needed to estimate this robustness, especially in the context of
      complex models. Here, we focused on the branch-site codon model. We investigated
      its robustness on a large set of simulated data. First, we investigated the
      impact of sequence divergence. We found evidence of underestimation of the
      synonymous substitution rate for values as small as 0.5, with a slight increase
      in false positives for the branch-site test. When dS increases further,
      underestimation of dS is worse, but false positives decrease. Interestingly, the
      detection of true positives follows a similar distribution, with a maximum for
      intermediary values of dS. Thus, high dS is more of a concern for a loss of power
      (false negatives) than for false positives of the test. Second, we investigated
      the impact of GC content. We showed that there is no significant difference of
      false positives between high GC (up to ~80%) and low GC (~30%) genes. Moreover,
      neither shifts of GC content on a specific branch nor major shifts in GC along
      the gene sequence generate many false positives. Our results confirm that the
      branch-site is a very conservative test.

PMID- 23558343
TI  - Analysis of dynamic smile and upper lip curvature in young Chinese.
AB  - During smile evaluation and anterior esthetic construction, the anatomic and
      racial variations should be considered in order to achieve better matching
      results. The aims of this study were to validate an objective method for
      recording spontaneous smile process and to categorize the smile and upper lip
      curvature of Chinese Han-nationality youth. One hundred and eighty-eight Chinese
      Han-nationality youths (88 males and 100 females) ranged from 20 to 35 years of
      age were selected. Spontaneous smiles were elicited by watching comical movies
      and the dynamics of the spontaneous smile were captured continuously with a
      digital video camera. All subjects' smiles were categorized into three types:
      commissure, cuspid and gummy smile based on video editing software and final
      images. Subjects' upper lip curvatures were also measured and divided into three
      groups: upward, straight and downward. Reliability analysis was conducted to
      obtain intra-rater reliabilities on twice measurements. The Pearson Chi-square
      test was used to compare differences for each parameters (alpha=0.05). In smile
      classification, 60.6% commissure smile, 33.5% cuspid smile and 5.9% gummy smile
      were obtained. In upper lip measurement, 26.1% upward, 39.9% straight and 34.0%
      downward upper lip curvature were determined. The commissure smile group showed
      statistically significant higher percentage of straight (46.5%) and upward
      (40.4%) in upper lip curvatures (P<0.05), while cuspid smile group (65.1%) and
      gummy smile group (72.7%) showed statistically significant higher frequency in
      downward upper lip curvature (P<0.05). It is evident that differences in upper
      lip curvature and smile classification exist based on race, when comparing
      Chinese subjects with those of Caucasian descent, and gender.

PMID- 23558344
TI  - Long-term observation of the mineral trioxide aggregate extrusion into the
      periapical lesion: a case series.
AB  - One-step apexification using mineral trioxide aggregate (MTA) has been reported
      as an alternative treatment modality with more benefits than the use of long-term
      calcium hydroxide for teeth with open apex. However, orthograde placement of MTA
      is a challenging procedure in terms of length control. This case series describes
      the sequence of events following apical extrusion of MTA into the periapical area
      during a one-step apexification procedure for maxillary central incisor with an
      infected immature apex. Detailed long-term observation revealed complete
      resolution of the periapical radiolucent lesion around the extruded MTA. These
      cases revealed that direct contact with MTA had no negative effects on healing of
      the periapical tissues. However, intentional MTA overfilling into the periapical
      lesion is not to be recommended.

PMID- 23558345
TI  - Atomically precise Au25 superatoms immobilized on CeO2 nanorods for styrene
      oxidation.
AB  - Atomically precise Au25 superatoms with electron-deficient Au12 shells and
      electron-rich Au13 cores immobilized on the surface of CeO2 nanorods achieved
      novel catalytic activity for styrene oxidation.

PMID- 23558347
TI  - H7N9 avian flu infects humans for the first time.

PMID- 23558346
TI  - New paralogues and revised time line in the expansion of the vertebrate GH18
      family.
AB  - Chitinase enzymes hydrolyse the polysaccharide chitin, an abundant architectural
      component in invertebrates and fungi. Most mammals encode at least two
      endochitinases (CHIT1 and CHIA/AMCase), as well as several homologues encoding
      catalytically inactive chitinase-like proteins or chilectins (all GH18 family
      proteins). It is becoming increasingly apparent that chitinases and chilectins
      play an important role in inflammation and their over-expression is correlated
      with numerous pathological conditions. We have conducted a detailed phylogenomic
      study of this gene family in order to understand its evolutionary history and the
      selection forces at work. The family has undergone extensive expansion,
      initiating with a duplication event at the root of the vertebrate tree generating
      the ancestors of CHIT1 and CHIA. Our analyses indicate that two further
      duplications of ancestral CHIA predate the divergence of bony fishes, one leading
      to a newly identified paralogous group (we have termed CHIO). In fish these
      sequences fall into two clades bearing the hallmarks of the teleost-specific
      genome duplication (referred to as 3R). In tetrapods, additional duplications
      predate and postdate the amphibian/mammalian split and relics of some exist as
      pseudogenes in the human genome. Expansion and selection of chilectins is
      pronounced in mammals and CHI3L1 (with a proposed function in immunity) is found
      in most mammals but not other vertebrates, while CHI3L2 is also evident in
      reptiles. Notably oviductin (OVGP1) became basic and gained a glycosylated tail
      with its evolving role in the mammalian reproductive system. In each case,
      retention of the sugar-binding barrel structure has constrained positive
      selection to limited sites.

PMID- 23558348
TI  - US panel rejects routine use of BRCA cancer screening in women.

PMID- 23558350
TI  - Dietary fat quality in regular fat diets has minor effects on biomarkers of
      inflammation in obese Zucker rats.
AB  - PURPOSE: Adipose tissue-associated chronic inflammation is involved in the
      pathogenesis of obesity-related diseases. Dietary fatty acids are known to
      influence inflammatory processes. The aim of this study was to investigate,
      whether diets with regular fat contents but variable fat qualities affect adipose
      tissue-associated inflammation through the fatty acid composition of mesenteric
      adipose tissue (MAT). METHODS: Obese Zucker rats were fed diets containing 7 %
      wt:wt rapeseed oil, corn oil, or lard for 10 weeks. Fatty acid composition and
      endocrine function regarding adipokines and cytokines of MAT, number of total
      CD3(+) T cells, and cytokine secretion of mesenteric lymph node (MLN)-derived
      lymphocytes were determined. Local effects in MAT and MLN were compared to
      systemic effects assessed in serum and peripheral blood mononuclear cells.
      RESULTS: Fatty acid composition of MAT reflected dietary fatty acid intake,
      without affecting endocrine function. Feeding the lard diet for 10 weeks
      increased the serum adiponectin and TNF-alpha secretion of blood lymphocytes,
      whereas CD3(+) T cells in blood were decreased. No effects were seen for the
      secretion of adipokines and cytokines from MAT, the amount of T cells in MLN, and
      cytokine secretion of MLN lymphocytes. CONCLUSIONS: In conclusion, feeding obese
      rats a diet with regular fat content but variable fat sources for 10 weeks,
      changed the fatty acid composition of MAT but not its secretory properties or MLN
      functions. Although the local immune system was not influenced, lard-feeding
      induced minor changes in systemic immune function.

PMID- 23558351
TI  - Urinary bisphenol A and obesity in U.S. children.
AB  - Childhood obesity, a major public health problem, can lead to cardiovascular
      disease in adulthood. Studies have implicated exposure to bisphenol A (BPA), a
      commonly used chemical, in the development of obesity in adults. However,
      literature is limited on this association in children. We examined the
      association between urinary BPA and obesity in children aged 6-18 years from the
      National Health and Nutrition Examination Survey (2003-2008). The primary
      exposure was urinary BPA and the outcome was obesity, defined as the >= 95th
      percentile of body mass index specific for age and sex. We found a positive
      association between increasing levels of urinary BPA and obesity, independent of
      age, sex, race/ethnicity, education, physical activity, serum cotinine, and
      urinary creatinine. Compared with children in the lowest quartile of BPA (<1.5
      ng/mL), children in the highest quartile (>5.4 ng/mL) had a multivariable odds
      ratio for obesity of 2.55 (95% confidence interval (CI): 1.65, 3.95) (Ptrend <
      0.01). The observed positive association was predominantly present in boys (odds
      ratio = 3.80, 95% CI: 2.25, 6.43) (Ptrend < 0.001) and in non-Hispanic whites
      (odds ratio = 5.87, 95% CI: 2.15, 16.05) (Ptrend < 0.01). In a representative
      sample of children, urinary BPA was associated with obesity, predominantly in non
      Hispanic white boys, independent of major risk factors.

PMID- 23558352
TI  - On a closed-form doubly robust estimator of the adjusted odds ratio for a binary
      exposure.
AB  - Epidemiologic studies often aim to estimate the odds ratio for the association
      between a binary exposure and a binary disease outcome. Because confounding bias
      is of serious concern in observational studies, investigators typically estimate
      the adjusted odds ratio in a multivariate logistic regression which conditions on
      a large number of potential confounders. It is well known that modeling error in
      specification of the confounders can lead to substantial bias in the adjusted
      odds ratio for exposure. As a remedy, Tchetgen Tchetgen et al. (Biometrika.
      2010;97(1):171-180) recently developed so-called doubly robust estimators of an
      adjusted odds ratio by carefully combining standard logistic regression with
      reverse regression analysis, in which exposure is the dependent variable and both
      the outcome and the confounders are the independent variables. Double robustness
      implies that only one of the 2 modeling strategies needs to be correct in order
      to make valid inferences about the odds ratio parameter. In this paper, I aim to
      introduce this recent methodology into the epidemiologic literature by presenting
      a simple closed-form doubly robust estimator of the adjusted odds ratio for a
      binary exposure. A SAS macro (SAS Institute Inc., Cary, North Carolina) is given
      in an online appendix to facilitate use of the approach in routine epidemiologic
      practice, and a simulated data example is also provided for the purpose of
      illustration.

PMID- 23558353
TI  - Risk of miscarriage among black women and white women in a U.S. Prospective
      Cohort Study.
AB  - Many adverse pregnancy outcomes differ by race. We examined the association
      between self-reported race and miscarriage (pregnancy loss at <20 weeks) in a
      community-based pregnancy cohort. Women from the southeastern United States
      (North Carolina, Texas, and Tennessee) were enrolled in "Right from the Start"
      from 2000 to 2009. They were recruited while trying to conceive or during early
      pregnancy. Participants completed study ultrasound examinations, interviews, and
      consent forms for review of medical records. We used proportional hazard models
      to examine miscarriage risk among black women compared with white women, adjusted
      for confounders. There were 537 observed miscarriages among 4,070 women, 23% of
      whom self-identified as black (n = 932). The life table-adjusted cumulative risk
      of loss after gestational week 5 was 21.3%. With adjustment for age and alcohol
      use, blacks had increased risk of miscarriage compared with whites (adjusted
      hazard ratio = 1.57, 95% confidence interval: 1.27, 1.93). When risk of loss
      before gestational week 10 was dichotomized at the median gestational age, there
      was little difference, but black women had a greater risk thereafter compared
      with white women (adjusted hazard ratio = 1.93, 95% confidence interval: 1.48,
      2.51). Early pregnancy ultrasound examinations did not differ by race. In
      summary, self-reported race is independently associated with risk of miscarriage,
      and the higher risk for black women is concentrated in gestational weeks 10-20.

PMID- 23558356
TI  - [Innovative integrated and coordinated care in pain therapy].

PMID- 23558355
TI  - Analysis of occupational asbestos exposure and lung cancer mortality using the g
      formula.
AB  - We employed the parametric G formula to analyze lung cancer mortality in a cohort
      of textile manufacturing workers who were occupationally exposed to asbestos in
      South Carolina. A total of 3,002 adults with a median age of 24 years at
      enrollment (58% male, 81% Caucasian) were followed for 117,471 person-years
      between 1940 and 2001, and 195 lung cancer deaths were observed. Chrysotile
      asbestos exposure was measured in fiber-years per milliliter of air, and annual
      occupational exposures were estimated on the basis of detailed work histories.
      Sixteen percent of person-years involved exposure to asbestos, with a median
      exposure of 3.30 fiber-years/mL among those exposed. Lung cancer mortality by age
      90 years under the observed asbestos exposure was 9.44%. In comparison with
      observed asbestos exposure, if the facility had operated under the current
      Occupational Safety and Health Administration asbestos exposure standard of <0.1
      fibers/mL, we estimate that the cohort would have experienced 24% less lung
      cancer mortality by age 90 years (mortality ratio = 0.76, 95% confidence
      interval: 0.62, 0.94). A further reduction in asbestos exposure to a standard of
      <0.05 fibers/mL was estimated to have resulted in a minimal additional reduction
      in lung cancer mortality by age 90 years (mortality ratio = 0.75, 95% confidence
      interval: 0.61, 0.92). 

PMID- 23558357
TI  - Airway salvation after failed anterior graft in a child with long segment
      stenosis.
AB  - OBJECTIVES: 1-Recognize difficulties and review techniques in long-segment
      laryngotracheal stenosis repair. 2-Contribute to increasing clinical and surgical
      skills in pediatric airway reconstruction through reporting our experience with a
      novel reconstruction technique involving use of a failed anterior graft and
      prolonged postoperative stenting. METHODS:  CASE REPORT: 10 year old male with
      history of burn injury who required a tracheostomy due to prolonged
      intubation/inhalational injury in 2005. Subglottic/tracheal stenosis was
      identified and he subsequently underwent anterior costal cartilage grafting
      involving the thyroid cartilage, cricoid cartilage, and trachea. He remained
      tracheostomy dependent for six years due to failed graft and postoperative
      complications despite several attempts to improve the airway with CO2 laser and
      balloon dilation. In 2011, preoperative CT with 3D reconstruction revealed a 32
      mm long segment of complete stenosis. The patient underwent suprahyoid release
      and single stage reconstruction with cricotracheal resection and partial
      preservation of the anterior costal cartilage graft found in the luminal scar
      tissue. RESULTS: Postoperatively the patient was stented with a nasal
      endotracheal tube for 2 weeks. Bronchoscopy showed mild tracheal collapse
      inferior to the site of anastamosis and granulation tissue at the site of
      anastomosis. Granulation tissue was removed and the subglottic anastomosis site
      was stented with a 2 cm Dumon stent for 6 months. CONCLUSION: The problem of long
      segment stenosis after failed cartilage graft reconstruction of the airway is
      evaluated and a novel technique of laryngotracheal reconstruction involving a pre
      existing failed anterior graft and short segment stenting is described.

PMID- 23558358
TI  - Vacuum assisted closure in the management of wound healing disorders in the head
      and neck: a retrospective analysis of 23 cases.
AB  - BACKGROUND: Since the middle of the 1990s vacuum-assisted closure (VAC) has been
      used in many areas of surgery to manage complex wounds and impaired wound
      healing. Until recently, little attention has been paid to this treatment
      modality in the field of head and neck surgery. The evaluation of its efficacy in
      wound healing disorders of the head and neck was the aim of this study. MATERIAL
      AND METHODS: Patients with complex wounds and impaired healing treated with VAC
      therapy between 2008 and 2011 were included into the study. VAC dressings were
      changed every 3 days and improvements in wound healing were documented. RESULTS:
      23 patients were treated with VAC therapy, in 18 cases (78%) closure of the
      defect could be reached without any further surgical procedure. 5 patients needed
      subsequent regional flap reconstruction to close the remaining defect. All of
      these patients had undergone salvage surgery in a previously irradiated neck
      before. CONCLUSION: Vacuum assisted closure is an effective treatment in the
      management of wound healing disorders and complex wounds in the head and neck. It
      offers a useful, non-invasive modality to close even large defects in the area.
      Previous irradiation seems to have a significant negative influence on the
      outcome of the therapy, but more data are required to assess these effects.

PMID- 23558359
TI  - Use of AlloDerm in primary reconstruction after resection of squamous cell
      carcinoma of the lip and oral commissure.
AB  - AlloDerm (LifeCell Corporation, Branchburg NJ) is an acellular dermal homograft
      processed from human cadaveric skin. AlloDerm has been used successfully for soft
      tissue reconstruction due to its lack of immunogenicity and minimal absorption.
      In the lip, it has been utilized for aesthetic lip augmentation and as an
      injectable filler. Description of its usage as an implant in primary lip
      reconstruction after tumor resection is limited. We describe the case of a 52
      year old male with a squamous cell carcinoma of the oral commissure and lower
      lip. After resection, the defect was reconstructed using implanted AlloDerm for
      bulk, a buccal mucosal advancement flap, and a cheek rhomboid flap. Lip mobility
      and oral competence were normal 3 months postoperatively. The reconstruction
      achieved adequate augmentation without significant resorption. AlloDerm should be
      considered in primary lip reconstruction after cancer resection.

PMID- 23558354
TI  - Association of adiposity genetic variants with menarche timing in 92,105 women of
      European descent.
AB  - Obesity is of global health concern. There are well-described inverse
      relationships between female pubertal timing and obesity. Recent genome-wide
      association studies of age at menarche identified several obesity-related
      variants. Using data from the ReproGen Consortium, we employed meta-analytical
      techniques to estimate the associations of 95 a priori and recently identified
      obesity-related (body mass index (weight (kg)/height (m)(2)), waist
      circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with
      age at menarche in 92,116 women of European descent from 38 studies (1970-2010),
      in order to estimate associations between genetic variants associated with
      central or overall adiposity and pubertal timing in girls. Investigators in each
      study performed a separate analysis of associations between the selected SNPs and
      age at menarche (ages 9-17 years) using linear regression models and adjusting
      for birth year, site (as appropriate), and population stratification.
      Heterogeneity of effect-measure estimates was investigated using meta-regression.
      Six novel associations of body mass index loci with age at menarche were
      identified, and 11 adiposity loci previously reported to be associated with age
      at menarche were confirmed, but none of the central adiposity variants
      individually showed significant associations. These findings suggest complex
      genetic relationships between menarche and overall obesity, and to a lesser
      extent central obesity, in normal processes of growth and development. 

PMID- 23558360
TI  - International multicenter tool to predict the risk of four or more tumor-positive
      axillary lymph nodes in breast cancer patients with sentinel node
      macrometastases.
AB  - Recently, many centers have omitted routine axillary lymph node dissection (ALND)
      after metastatic sentinel node biopsy in breast cancer due to a growing body of
      literature. However, existing guidelines of adjuvant treatment planning are
      strongly based on axillary nodal stage. In this study, we aim to develop a novel
      international multicenter predictive tool to estimate a patient-specific risk of
      having four or more tumor-positive axillary lymph nodes (ALN) in patients with
      macrometastatic sentinel node(s) (SN). A series of 675 patients with
      macrometastatic SN and completion ALND from five European centers were analyzed
      by logistic regression analysis. A multivariate predictive model was created and
      validated internally by 367 additional patients and then externally by 760
      additional patients from eight different centers. All statistical tests were two
      sided. Prevalence of four or more tumor-positive ALN in each center's series (P =
      0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P =
      0.003), histological size of the primary tumor (P = 0.020), and extra-capsular
      extension of SN metastasis (P < 0.0001) were included in the predictive model.
      The model's area under the receiver operating characteristics curve was 0.766 in
      the internal validation and 0.774 in external validation. Our novel international
      multicenter-based predictive tool reliably estimates the risk of four or more
      axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our
      tool performs well in internal and external validation, but needs to be further
      validated in each center before application to clinical use.

PMID- 23558361
TI  - The Vitamin D paradox: bone density testing in females aged 45 to 74 did not
      increase over a ten-year period despite a marked increase in testing for vitamin
      D.
AB  - AIM: To determine whether increased vitamin D testing resulted in improved
      osteoporosis detection in Australian females aged 45-74 yr. METHODS: Longitudinal
      analysis of bone densitometry, 25-hydroxyvitamin D (25(OH)D) and full blood count
      (FBC) testing between 2001 and 2011. The number and rate of tests per 100,000
      individuals and benefit in dollars for bone densitometry, 25(OH)D and FBC from
      2001-2011 for individuals aged 45-74 yr were obtained from Medicare Australia.
      RESULTS: There was a disproportionate increase in 25(OH)D testing compared to
      bone density testing from 2001 to 2011, whereby 25(OH)D testing increased from
      26,666 to 1.65 million p.a. and bone density testing increased from 41,453 to
      66,100 p.a. Bone densitometry increased approximately 1.2 fold, whereas 25(OH)D
      testing increased by 55.2, 41.2 and 34.3 fold in females aged 45-54, 55-64 and 65
      74 yr, respectively. This represents an increase in annual benefits from
      approximately $2.5-$4.1 million for bone density testing and $0.7-$40.5 million
      for 25(OH)D testing over the period. CONCLUSIONS: This study demonstrates that
      improved detection of vitamin D deficiency is not being translated into better
      detection in at-risk women of the consequences of vitamin D deficiency on target
      organs such as bone. This failure to translate rising awareness and better
      detection of vitamin D deficiency into physiological outcomes is a massive missed
      opportunity for improved bone health and reduced fracture risk.We propose that
      clinical practice guidelines be introduced not only for the purpose of diagnosis
      and testing for vitamin D, but to include recommendations for bone health testing
      in at-risk individuals.

PMID- 23558362
TI  - Streptococcus bovis/Streptococcus equinus complex fecal carriage, colorectal
      carcinoma, and infective endocarditis: a new appraisal of a complex connection.
AB  - The proportion of group D streptococcal infective endocarditis (IE)
      (predominantly due to Streptococcus gallolyticus) and the incidence of colorectal
      cancer are higher in France than in most European countries. We assumed that this
      could be explained by a high group D streptococci (GDS) fecal carriage rate. The
      aims of this study were to re-assess the GDS fecal carriage rate in France and
      its relationship with colorectal cancer. Consecutive adult subjects who were to
      undergo a complete colonoscopy were invited to participate. GDS were searched in
      subjects' stools before their colonoscopy using biomolecular techniques.
      Colonoscopic findings were sorted into four subgroups: normal colonoscopy, non
      tumoral lesions, benign tumors, and premalignant/malignant tumors. GDS fecal
      carriages were calculated overall and in each subgroup and compared. The data
      from 259 subjects were analyzed. GDS were identified in the feces of 12 subjects,
      with the following distribution: S. lutetiensis (n = 9), S. pasteurianus (n = 2),
      and S. gallolyticus (n = 1). This accounted for an overall GDS fecal carriage
      rate of 4.6 %. The GDS fecal carriage rate was 6 % in case of normal colonoscopy,
      1.3 % in case of non-tumoral lesions, 3.2 % in case of benign tumors, and 11 % in
      case of premalignant/malignant tumors. These four percentages were not
      statistically different. The GDS fecal carriage rate was lower than expected,
      which did not confirm our working hypothesis. Most strains belonged to S. bovis
      biotype II, while S. gallolyticus was found only once. These findings suggest
      that different GDS play different roles in the etiopathogenesis of IE and
      colorectal cancer.

PMID- 23558363
TI  - Impact of ribotype 027 on Clostridium difficile infection in a geriatric
      department.
AB  - The purposes of this study were to describe the epidemiology (2001-2009) of
      Clostridium difficile infections (CDI) in a geriatric department and to compare
      the clinical data of patients infected with a 027 or non-027 strain. We
      retrospectively identified all geriatric patients with CDI and analysed the
      clinical and microbiological data of 133 patients for whom a ribotype was
      available between March 2003 and December 2009. The incidence of CDI in our
      geriatric department increased from 0.2 per 100 admissions in 2001 to 8.1 in 2004
      and decreased to 1.3 in 2008 before a new rise to 2.1 in 2009. The percentage of
      ribotype 027 decreased from 2007 but it remained the most prevalent ribotype
      during the years 2007-2009, with a greater dispersion of ribotypes. The mean age
      of the patients was 84 years and the median Charlson index was 6.0. Previous use
      of fluoroquinolones was a significant risk factor for developing a CDI with an
      027 strain (p = 0.001). Cure was significantly lower in the 027 group (p =
      0.003). The total attributable mortality was 24.1 %. A multiparametric model
      showed that attributable mortality was influenced by the ribotype 027 (p =
      0.037), the severity of clinical symptoms (p = 0.001) and the type of treatment
      (p = 0.002). Oral vancomycin had a protective effect against mortality. Attention
      should be paid to elderly patients developing a CDI, especially after the
      administration of fluoroquinolones. Oral vancomycin could be recommended as the
      first-line agent not only to protect against recurrence or severe CDI, but to
      diminish the attributable mortality risk.

PMID- 23558364
TI  - Paediatric epidemiology of Pasteurella multocida meningitis in France and review
      of the literature.
AB  - We report on six cases of Pasteurella multocida (P. multocida) meningitis
      occurring between 2001 and 2011 by a French nationwide active surveillance
      network of paediatric bacterial meningitis (ACTIV/GPIP). The cases accounted for
      0.15 % of the paediatric meningitis cases reported between 2001 and 2011 in
      France, all in infants <4 months old. A review of the literature allowed us to
      gather information on 42 other cases of P. multocida meningitis in infants <1
      year old reported since 1963. Among all 48 cases, 44 % were newborns. An animal
      source of the infection, including 39 household dogs and cats, was suspected or
      identified in 42 of 48 cases. A traumatic contact between the child and a pet
      occurred in 8 % of cases, and a vertical transmission from mother to child during
      birth in 10.4 %. Most of the time, the infection resulted from non-traumatic
      contact between the child and the pet, through licking or sniffing. The absence
      of host risk factors suggests that an immature immune system is responsible,
      given the young age of the children. Although complications, especially
      neurological lesions, were not rare (37.5 %), the long-term outcome was usually
      good. Four infants died of meningitis. This rare disease could be prevented by
      reducing contact between infants and household pets, and by performing simple
      hygiene measures before handling babies.

PMID- 23558367
TI  - Ferroelectric polymer-gated graphene memory with high speed conductivity
      modulation.
AB  - The feasibility of a high speed ferroelectric graphene memory device using a
      ferroelectric polymer (PVDF-TrFE)/graphene stack has been demonstrated. The
      conductivity of this metal-ferroelectric-graphene (MFG) device could be modulated
      up to 775% with a very fast programming speed down to 10 ns. Also, programmed
      states were maintained up to 1000 s with endurance over 1000 cycles. In addition
      to demonstrating a single memory device, the array-level integration and cell
      write/read functionality of a 4 * 4 MFG array adopting a graphene bit line has
      also been confirmed to show the feasibility of MFG memory.

PMID- 23558366
TI  - Antibiotic susceptibility profiles of neonatal invasive isolates of Escherichia
      coli from a 2-year nationwide surveillance study in Germany, 2009-2010.
AB  - A nationwide 2-year surveillance study on invasive neonatal Escherichia coli
      infections in Germany was conducted. A total of 158 isolates were tested for
      antibiotic susceptibility. The empirical treatment regimen of ampicillin plus
      gentamicin for neonatal sepsis appears to remain effective, but emerging
      resistance needs to be closely monitored. 

PMID- 23558365
TI  - High abundance and diversity of antimicrobial resistance determinants among early
      vancomycin-resistant Enterococcus faecium in Poland.
AB  - The purpose of this study was to investigate the clonal structure, antimicrobial
      resistance phenotypes and their determinants among early vancomycin-resistant
      Enterococcus faecium (VREm) isolates in Poland. Two hundred and eighty-one VREm
      isolates collected between 1997 and 2005 were studied. VREm isolates were
      characterised by multilocus sequence typing (MLST). The presence of antimicrobial
      resistance determinants, transposon-specific genes, IS16 and esp Efm was checked
      by polymerase chain reaction (PCR). Ciprofloxacin and ampicillin resistance
      determinants were investigated by sequencing. Two hundred and twenty-two (79 %)
      and 59 (21 %) VREm isolates were vanA- and vanB-positive, respectively. Among 135
      representative isolates, MLST yielded 33 different sequence types (STs), of which
      29 were characteristic of hospital-associated E. faecium; 128 (94.8 %) and 123
      (91.1 %) isolates harboured the IS16 and esp Efm genes, and all 135 isolates were
      resistant to ciprofloxacin and ampicillin. Resistance to tetracycline (71.1 %
      isolates) was mostly associated with tetM (75.0 %) and the concomitant presence
      of the Tn916 integrase gene. High-level resistance to streptomycin (93.3 % of
      isolates) and high-level resistance to gentamicin (94.1 % of isolates) were due
      to ant(6')-Ia and aac(6')-Ie-aph(2") genes, respectively, the latter of which is
      known to be located on various Tn4001-type transposons. Fifteen combinations of
      mutations in the quinolone-determining regions of GyrA and ParC were identified,
      including changes not previously reported, such as S83F and A84P in GyrA. Twenty
      three variants of the penicillin-binding protein PBP5 occurred in the studied
      group, and novel insertions at amino acid positions 433 and 568 were identified.
      This analysis revealed the predominance of hospital-associated strains of E.
      faecium, carrying an abundant and divergent range of resistance determinants
      among early VREm isolates in Poland.

PMID- 23558368
TI  - Measurement of the interface tension of smectic membranes in water.
AB  - A simple method is proposed to measure the interfacial tension of a smectic
      liquid crystal (LC) in freely suspended film geometry in aqueous environment. The
      method is based upon the evaluation of the deformation of smectic bubbles by the
      buoyancy of a trapped air volume. The advantages over classical suspended smectic
      droplet experiments in water are the considerably shorter equilibration times,
      and most important, the much larger density differences between the fluids. The
      latter allow a much more accurate force determination. Bulk elastic force
      contributions can be practically neglected in the thin smectic films. Values for
      a smectic C mixture of two disubstituted phenylpyrimidines are reported.

PMID- 23558369
TI  - Fascia lliaca block for analgesia after hip arthroplasty: a randomized double
      blind, placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Fascia iliaca block (FIB) is often used to treat pain
      after total hip arthroplasty (THA), despite a lack of randomized trials to
      evaluate its efficacy for this indication. The objective of this study was to
      assess the analgesic benefit of FIB after THA. Our primary hypothesis was
      administration of FIB decreases the intensity of postoperative pain (numeric
      rating scale [NRS-11] score) compared with sham block (SB) in patients after THA.
      METHODS: After institutional review board approval and informed consent, 32
      eligible patients having THA were recruited. In the postoperative care unit,
      although all patients received intravenous morphine sulfate patient-controlled
      analgesia, patients reporting pain of 3 or greater on the NRS-11 scale were
      randomized to receive ultrasound-guided fascia iliaca (30 mL 0.5% ropivacaine) or
      SB (30 mL 0.9% NaCl) using identical technique, below fascia iliaca. The primary
      outcome was pain intensity (NRS-11) after FIB. RESULTS: Thirty-two patients (16
      in each group) completed the study; all patients received an FIB. There was no
      difference in pain intensity (NRS-11 = 5.0 +/- 0.6 vs 4.7 +/- 0.6, respectively)
      after FIB versus SB or in opioid consumption (8.97 +/- 1.6 vs 5.7 +/- 1.6 mg
      morphine, respectively) between the groups at 1 hour. The morphine consumption
      after 24 hours was similar in both groups (49.0 +/- 29.9 vs 50.4 +/- 34.5 mg, P =
      0.88, respectively). CONCLUSIONS: The evidence in these data suggests that the
      difference in average pain intensity after FIB versus SB was not significant (95%
      confidence interval, -2.2-1.4 NRS units).

PMID- 23558370
TI  - A randomized comparison between ultrasound- and fluoroscopy-guided third
      occipital nerve block.
AB  - BACKGROUND: Third occipital nerve block (TONB) is commonly used in the diagnosis
      and treatment of upper neck pain and cervicogenic headaches. Although fluoroscopy
      is the current imaging standard for TONB, ultrasound (US) guidance offers a
      promising, radiation-free alternative. In this randomized, observer-blinded
      trial, we compared the 2 imaging modalities. Our research hypothesis was that US
      guidance would result in a shorter performance time. METHODS: Forty patients
      undergoing TONB were randomized to fluoroscopy or US guidance. A mixture of local
      anesthetic and radiographic contrast was injected in both groups. The primary
      outcome was performance time. Secondary outcomes included success rate, pain
      levels before and after block, area of sensory hypoesthesia, quality of the block
      (assessed by electrical perceptual threshold), and procedure-related
      complications. RESULTS: Ultrasound guidance was associated with a significantly
      shorter performance time (212.8 vs 396.5 seconds; P = 0.000) and fewer needle
      passes (2 vs 6; P = 0.000). Both imaging modalities, however, resulted in similar
      success rates (95%-100%). Furthermore, no intergroup differences were found in
      preblock and postblock pain scores. In both groups, TONB produced hypoesthesia
      that was most profound in the suboccipital region. In the fluoroscopy group, C2
      C3 intra-articular spread of radiographic contrast and vascular breach were noted
      in 15% and 10% of patients, respectively. In contrast, no adverse events occurred
      with US guidance. CONCLUSIONS: Fluoroscopy and US guidance provide similar
      success rates for TONB. However, ultrasonography is associated with improved
      efficiency (decreased performance time, fewer needle passes).

PMID- 23558371
TI  - Sleep apnea and total joint arthroplasty under various types of anesthesia: a
      population-based study of perioperative outcomes.
AB  - BACKGROUND AND OBJECTIVES: The presence of sleep apnea (SA) among surgical
      patients has been associated with significantly increased risk of perioperative
      complications. Although regional anesthesia has been suggested as a means to
      reduce complication rates among SA patients undergoing surgery, no data are
      available to support this association. We studied the association of the type of
      anesthesia and perioperative outcomes in patients with SA undergoing joint
      arthroplasty. METHODS: Drawing on a large administrative database (Premier Inc),
      we analyzed data from approximately 400 hospitals in the United States. Patients
      with a diagnosis of SA who underwent primary hip or knee arthroplasty between
      2006 and 2010 were identified. Perioperative outcomes were compared between
      patients receiving general, neuraxial, or combined neuraxial-general anesthesia.
      RESULTS: We identified 40,316 entries for unique patients with a diagnosis for SA
      undergoing primary hip or knee arthroplasty. Of those, 30,024 (74%) had
      anesthesia-type information available. Approximately 11% of cases were performed
      under neuraxial, 15% under combined neuraxial and general, and 74% under general
      anesthesia. Patients undergoing their procedure under neuraxial anesthesia had
      significantly lower rates of major complications than did patients who received
      combined neuraxial and general or general anesthesia (16.0%, 17.2%, and 18.1%,
      respectively; P = 0.0177). Adjusted risk of major complications for those
      undergoing surgery under neuraxial or combined neuraxial-general anesthesia
      compared with general anesthesia was also lower (odds ratio, 0.83 [95% confidence
      interval, 0.74-0.93; P = 0.001] vs odds ratio, 0.90 [95% confidence interval,
      0.82-0.99; P = 0.03]). CONCLUSIONS: Barring contraindications, neuraxial
      anesthesia may convey benefits in the perioperative outcome of SA patients
      undergoing joint arthroplasty. Further research is needed to enhance an
      understanding of the mechanisms by which neuraxial anesthesia may exert
      comparatively beneficial effects.

PMID- 23558372
TI  - Ultrasound-guided popliteal block through a common paraneural sheath versus
      conventional injection: a prospective, randomized, double-blind study.
AB  - BACKGROUND AND OBJECTIVES: The macroscopic anatomy of a common paraneural sheath
      that surrounds the sciatic nerve in the popliteal fossa has been studied recently
      in a human cadaveric study. It has been suggested that an injection through this
      sheath could be an ideal location for local anesthetic administration for
      popliteal block. The aim of the present study was to evaluate the hypothesis that
      popliteal sciatic nerve blockade through a common paraneural sheath results in
      shorter onset time when compared with conventional postbifurcation injection
      external to the paraneural tissue. To illustrate the microscopic anatomy of the
      paraneural tissues, we performed histological examinations of a human leg
      specimen. METHODS: Following institutional review board approval and written
      informed consent, 89 patients undergoing an ultrasound-guided popliteal block for
      foot or ankle surgery were included in the study. They were prospectively
      randomized to receive a single injection of local anesthetic at the site of
      bifurcation through a common paraneural sheath (group 1) or 2 separate
      circumferential injections of the tibial and common peroneal nerves distally to
      sciatic nerve bifurcation (group 2). RESULTS: Patients in group 1 had a 30%
      shorter onset time of both sensory and motor block. This was associated with a
      more extensive proximal and distal longitudinal spread of local anesthetic in
      this group. Nerve diameter and cross-sectional area remained unchanged in both
      groups after injection, which is consistent with extraneural injection. A greater
      proportion of patients in group 1 required a single needle pass for block
      performance. DISCUSSION: An ultrasound-guided popliteal sciatic nerve block
      through a common paraneural sheath at the site of sciatic nerve bifurcation is a
      simple, safe, and highly effective block technique. It results in consistently
      short onset time, while respecting the integrity of the epineurium and
      intraneural structures.

PMID- 23558373
TI  - The myth of the equiangular triangle for identification of sacral hiatus in
      children disproved by ultrasonography.
AB  - BACKGROUND AND OBJECTIVES: A triangle formed by the sacral hiatus and posterior
      superior iliac spines (PSISs) has been known as equiangular and has been proposed
      as a way to help identify the sacral hiatus for a caudal block. In children,
      however, no feasibility study of this triangle has been performed. We compared
      the expected sacral hiatus obtained from the equiangular triangle method and the
      real sacral hiatus confirmed by ultrasound. METHODS: Eighty children (aged 0.5-72
      months) were placed in the left lateral decubitus position in full hip flexion.
      The vertex of an equiangular triangle formed inferior to PSISs was considered as
      the expected sacral hiatus by classic bony landmarks. The real sacral hiatus was
      identified by ultrasound. The angle formed by the 2 lines connecting each PSIS
      and the real sacral hiatus (angle theta) was also measured. The distances between
      the midpoint of PSISs and expected sacral hiatus (distance E) and real sacral
      hiatus (distance R) were measured and compared. RESULTS: The angle theta was
      greater than 60 degrees in all children (79.3 [9.3] degrees) and negatively
      correlated with age younger than 1 year. Distance R (3.5 [1.1] cm) was
      significantly shorter than distance E (4.9 [1.2] cm) (P< 0.001). The distance R
      positively correlated with age, weight, height, and the distance between the
      PSISs. CONCLUSIONS: In children, using the equiangular triangle to identify the
      sacral hiatus may be inappropriate because the actual triangle formed by the
      sacral hiatus and PSISs is not equiangular.

PMID- 23558374
TI  - Enhanced desulfurizing flotation of coal using sonoelectrochemical method.
AB  - Enhanced desulfurizing flotation of low sulfur coal was investigated using
      sonoelectrochemical method. The supporting electrolyte used in this process was
      sodium chloride and the additive was anhydrous ethanol. The effects of treatment
      conditions on desulfurization were studied by a single-factor method. The
      conditions include anhydrous ethanol concentration, sodium chloride
      concentration, sonoelectrolytic voltage, sonoelectrolytic temperature,
      sonoelectrolytic time and coal sample granulometry. The optimal experimental
      conditions achieved for anhydrous ethanol concentration, sodium chloride
      concentration, sonoelectrolytic voltage, sonoelectrolytic temperature and
      sonoelectrolytic time are 1.7 mol L(-1), 5.1*10(-3) mol L(-1), 10 V, 70  degrees
      C, 50 min achieved for a -0.18 mm coal sample. Optimal conditions cause a sulfur
      reduction of up to 69.4%. The raw and treated coals were analyzed by infrared
      spectroscopy and a chemical method. Pyritic sulfur, organic sulfur, ash as well
      as moisture are partially removed. The combination of high sulfur reduction, high
      yield, as well as high ash reduction was obtained in the newly developed method
      of enhanced flotation by sonoelectrochemistry. Ultrasound irradiation promotes
      electron transfer efficiency and increases clean coal yield.

PMID- 23558376
TI  - Antibody response to Mycoplasma capricolum subsp. capripneumoniae bacterium in
      small holder dairy goats in Tanzania.
AB  - Contagious caprine pleuropneumonia (CCPP), an Office International des Epizooties
      listed disease, can cause significant levels of morbidity and mortality in goats
      in Africa, the Middle East, and Western Asia. A cross-sectional study was
      conducted to determine the seroprevalence of CCPP, in two contrasting
      administrative districts of northern Tanzania, namely, Babati and Arumeru. A
      total of 337 serum samples were collected from January to July 2010, from
      apparently clinically healthy unvaccinated dairy goats breeds of different ages
      and sexes. Samples were subjected to monoclonal antibody-based competitive enzyme
      linked immunosorbent assay for the specific measurement of antibodies to
      Mycoplasma capricolum subsp. capripneumoniae bacterium. The overall animal flock
      and village-level seroprevalence of CCPP was found to be 3.3 % [95 % confidence
      interval (CI) = 1.6-5.8], 9.6 % (95 % CI = 4.7-16.9), and 31.5 % (95 % CI = 15.6
      56.5), respectively. There was no evidence (p = 0.659) of differences in
      seroprevalence between samples from the two administrative locations. Despite the
      fact that there was no significant difference (p > 0.05) in seropositivity
      between sex and age and between breeds sampled, there was a significant
      difference (p < 0.05) in seropositivity between the different physiological
      status groups examined with the non-lactating (dry) category of goats showing a
      higher seroprevalence. The findings of this survey revealed evidence of dairy
      goat exposure to M. capricolum subsp. capripneumoniae, although at a low
      prevalence. It is therefore advisable to include CCPP serology in the
      seromonitoring program so as to give a better indication of flock immunity. This
      should lead to the establishment of appropriate CCPP control measures in
      smallholder dairy goat flocks, which are increasingly being recognized for their
      value as a vital source of livelihood for resource poor livestock keepers in
      Tanzania.

PMID- 23558375
TI  - Bacterial expression strategies for several Sus scrofa diacylglycerol kinase
      alpha constructs: solubility challenges.
AB  - We pursued several strategies for expressing either full-length Sus scrofa
      diacylglycerol kinase (DGK) alpha or the catalytic domain (alphacat) in
      Escherichia coli. Alphacat could be extracted, refolded, and purified from
      inclusion bodies, but when subjected to analytical gel filtration chromatography,
      it elutes in the void volume, in what we conclude are microscopic aggregates
      unsuitable for x-ray crystallography. Adding glutathione S-transferase,
      thioredoxin, or maltose binding protein as N-terminal fusion tags did not improve
      alphacat's solubility. Coexpressing with bacterial chaperones increased the yield
      of alphacat in the supernatant after high-speed centrifugation, but the protein
      still elutes in the void upon analytical gel filtration chromatography. We
      believe our work will be of interest to those interested in the structure of
      eukaryotic DGKs, so that they know which expression strategies have already been
      tried, as well as to those interested in protein folding and those interested in
      chaperone/target-protein interactions.

PMID- 23558377
TI  - Effect of Brazilian red propolis administration on hematological, biochemical
      variables and parasitic response of Santa Ines ewes during and after flushing
      period.
AB  - Brazilian red propolis was administered orally to Santa Ines ewes, and evaluation
      was made of general health and hematological, biochemical, and parasitic
      responses during and after flushing. Thirty mature, nonlactating, nonpregnant
      Santa Ines ewes (40 +/- 2 kg and 2.5 years old) were grazing tropical pasture
      (Brachiaria decumbens and Pennisetum purpureum) and, as flushing after
      synchronization, were supplemented with a concentrate-roughage mixture at a rate
      of 4 % body weight (BW). Ewes were divided according to BW and fecal egg count
      (FEC) into two groups (n = 15 each): control and propolis that received propolis
      ethanolic extract at rates of, respectively, 0 and 3 g/ewe/day. The treatments
      lasted 21 days until the end of flushing period. BW and body condition score
      (BCS) were recorded, and blood and fecal samples were taken weekly for 8 weeks.
      Mean values of BW and BCS were not (P > 0.05) affected by propolis
      administration. Propolis increased (P < 0.01) total leukocytes (WBC), but no
      significant differences were observed for other hematological parameters.
      Propolis increased (P < 0.01) total protein and globulin concentrations and
      decreased (P < 0.01) triglycerides, glutamate oxaloacetate transaminase, and
      glutamate pyruvate transaminase. Propolis decreased (P < 0.05) FEC. Propolis
      administration had good impact on ewe health and may be a promising feed additive
      during critical periods such as flushing.

PMID- 23558378
TI  - Biological therapies for rheumatoid arthritis: progress to date.
AB  - Biologic drugs for the management of rheumatoid arthritis (RA) have
      revolutionized the therapeutic armamentarium with the development of several
      novel monoclonal antibodies, which include murine, chimeric, humanized, fully
      human antibodies and fusion proteins. These biologics bind to their targets with
      high affinity and specificity. Since 1998, nine different biologics have been
      approved by the US Food and Drug Administration (FDA) and European Medicines
      Agency (EMA) for the treatment of RA, and several others are in different stages
      of clinical trials. This field is in continuous evolution and new biologics are
      tested every year. Therefore a precise analysis is required in order to have a
      detailed and updated state of the art of this field. In this review, our main aim
      is to analyse all available biological therapies that are FDA and EMA approved
      for the treatment of RA and also those that are in clinical trials for the
      management of RA patients. 

PMID- 23558379
TI  - The outlook for alemtuzumab in multiple sclerosis.
AB  - Alemtuzumab is a humanized anti-CD52 monoclonal antibody. Treatment in humans
      results in a rapid, profound, and prolonged B- and T-cell lymphopenia.
      Subsequently, lymphocyte reconstitution by homeostatic mechanisms alters the
      composition, phenotype, and function of T-cell subsets, thus allowing the immune
      system to be 'reset'. One phase II and two phase III randomized, multicenter,
      single-blinded (outcomes assessor) clinical trials of alemtuzumab in relapsing
      remitting multiple sclerosis have now been completed. Against an active
      comparator and the current first-line therapy for relapsing-remitting multiple
      sclerosis (interferon-beta), alemtuzumab showed a significant reduction in
      annualized relapse rate as well as a significant reduction in the accumulation of
      disability. These outcomes are sustained over at least 5 years following
      treatment. The most common adverse effects are mild infusion reactions, an
      increased incidence of mild-to-moderate severity infections and secondary
      autoimmunity. The latter is observed in a third of treated patients, commonly
      thyroid disease but other target cells have been described including cytopenias.
      Marketing authorization applications have been submitted for the use of
      alemtuzumab in multiple sclerosis to the Food and Drug Administration and the
      European Medicines Agency, with licensing expected in 2013. Here, we discuss the
      outlook for alemtuzumab in multiple sclerosis in light of the currently available
      therapies, outcomes of and lessons learnt from clinical trials, and the overall
      position of monoclonal antibodies in modern treatment strategies.

PMID- 23558380
TI  - Protein-coated nanofibers for promotion of T cell activity.
AB  - We have demonstrated that stable Concanavalin A (Con A)-coated supramolecular
      nanofibers can be constructed by complexation of self-assembled mannose
      nanofibers with Con A. The extended multivalent Con A nanofibers bind strongly to
      T cell surfaces and promote T cell activation.

PMID- 23558381
TI  - [New trends and concepts in diagnosis and treatment of achalasia].
AB  - The last 2 decades have witnessed a revolution in the treatment of esophageal
      achalasia. Nowadays, laparoscopic Heller myotomy with partial fundoplication is
      considered in most centers the primary treatment modality, while endoscopic
      treatment, i.e. pneumatic dilatation, is mainly reserved for the management of
      patients unfit for surgery or in case of surgical failure. Recently, a new
      approach to achalasia has been proposed: the peroral endoscopic myotomy (POEM),
      which combines the advantages of endoscopy and surgery. This article reviews the
      evolution of the diagnosis and treatment of esophageal achalasia during the last
      20 years.

PMID- 23558382
TI  - Cross-cultural and site-based influences on demographic, well-being, and social
      network predictors of risk perception in hazard and disaster settings in Ecuador
      and Mexico: predictors of risk perception in hazard and disaster settings in
      Ecuador and Mexico.
AB  - Although virtually all comparative research about risk perception focuses on
      which hazards are of concern to people in different culture groups, much can be
      gained by focusing on predictors of levels of risk perception in various
      countries and places. In this case, we examine standard and novel predictors of
      risk perception in seven sites among communities affected by a flood in Mexico
      (one site) and volcanic eruptions in Mexico (one site) and Ecuador (five sites).
      We conducted more than 450 interviews with questions about how people feel at the
      time (after the disaster) regarding what happened in the past, their current
      concerns, and their expectations for the future. We explore how aspects of the
      context in which people live have an effect on how strongly people perceive
      natural hazards in relationship with demographic, well-being, and social network
      factors. Generally, our research indicates that levels of risk perception for
      past, present, and future aspects of a specific hazard are similar across these
      two countries and seven sites. However, these contexts produced different
      predictors of risk perception-in other words, there was little overlap between
      sites in the variables that predicted the past, present, or future aspects of
      risk perception in each site. Generally, current stress was related to perception
      of past danger of an event in the Mexican sites, but not in Ecuador; network
      variables were mainly important for perception of past danger (rather than future
      or present danger), although specific network correlates varied from site to site
      across the countries.

PMID- 23558384
TI  - Retraction.

PMID- 23558383
TI  - Reference values for vastus lateralis fiber size and type in healthy subjects
      over 40 years old: a systematic review and metaanalysis.
AB  - Skeletal muscle atrophy is a major systemic impairment in chronic diseases. Yet
      its determinants have been hard to identify because a clear research definition
      has not been agreed upon. The reduction in muscle fiber cross-sectional area
      (CSA) is a widely acknowledged marker of muscle atrophy, but no reference values
      for the muscle fiber CSA at the age of the onset of chronic disease have ever
      been published. Thus, we aimed to systematically review the studies providing
      data on fiber CSA and fiber type proportion in the vastus lateralis of the
      quadriceps of healthy subjects (age >40 yr) and then to pool and analyze the data
      from the selected studies to determine reference values for fiber CSA. We
      followed the guidelines of the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) and identified 19 studies, including 423 subjects that
      matched the inclusion criteria. On the basis of fiber type and gender, the mean
      fiber CSA and the lower limits of normal (LLNs) were (%type I*60) + 1,743 MUm(2)
      and (%type I*60) - 718 MUm(2), respectively, for men; and (%type I*70) + 139
      MUm(2) and (%type I*70) - 1,485 MUm(2), respectively, for women. There was no
      significant heterogeneity among subgroups of fiber type and gender. The pooled
      type I fiber proportion was 50.3% (LLN = 32.9%). In multivariate analysis, fiber
      CSA was significantly correlated with Vo2 peak (r = 190.92; P = 0.03), and type I
      fiber proportion was correlated with age (r = -0.024; P = 0.005), body mass index
      (r = 0.096; P = 0.005), and Vo2 peak (r = -0.053; P = 0.005). Our metaanalysis of
      a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA
      according to fiber type and gender. This analysis will be improved by prospective
      assessment in well-characterized healthy subjects. 

PMID- 23558385
TI  - Historical Perspective: Harvey's epoch-making discovery of the Circulation, its
      historical antecedents, and some initial consequences on medical practice.
AB  - In Harvey's Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus of
      1628, we see the mechanisms of the Circulation worked out more or less in full
      from the results of experimental demonstration, virtually complete but for the
      direct visual evidence of a link between the minute final terminations and
      initial branches of the arterial and venous systems, respectively. This would
      become available only when the capillaries could be seen under the microscope, by
      Malpighi. Harvey's amazingly modern order of magnitude analysis of volumetric
      circulatory flow and appreciation of the principle of continuity (mass
      conservation), his adroit investigational uses of ligatures of varying tightness
      in elegant flow experiments, and his insightful deductions truly explain the
      movement of the blood in animals. His end was accomplished. So radical was his
      discovery that early in the 18th century, the illustrious Hermann Boerhaave,
      professor of medicine at Leyden, declared that nothing that had been written
      before Harvey was worthy of consideration any more. The conclusions of De Motu
      Cordis are unassailable and beautiful in their simplicity. Harvey's genius and
      tireless determination have served physiology and medicine well.

PMID- 23558386
TI  - Acute superoxide scavenging reduces sympathetic vasoconstrictor responsiveness in
      short-term exercise-trained rats.
AB  - We hypothesized that acute superoxide (O2(-)) scavenging would attenuate
      sympathetic vasoconstrictor responsiveness by augmenting nitric oxide (NO)
      mediated inhibition of sympathetic vasoconstriction in exercise-trained rats.
      Sprague-Dawley rats were randomly assigned to sedentary time control (S; n = 7)
      or mild- (M: 20 m/min, 5 degrees  grade; n = 7) or heavy-intensity (H: 40 m/min,
      5 degrees  grade; n = 7) exercise training (ET) groups and trained 5 days/wk for
      4 wk with matched training volume. Following ET, rats were anesthetized and
      instrumented for lumbar sympathetic chain stimulation and measurement of femoral
      vascular conductance. In resting skeletal muscle, the percentage change of
      femoral vascular conductance in response to continuous (2 Hz) and patterned (20
      and 40 Hz) sympathetic stimulation was determined during control conditions, O2(
      ) scavenging (TIRON, 1 g.kg(-1).h(-1) iv) and combined O2(-) scavenging + nitric
      oxide synthase blockade (N(omega)-nitro-l-arginine methyl ester, 5 mg/kg iv). ET
      augmented the vasoconstrictor response to sympathetic stimulation in a training
      intensity-dependent manner (P < 0.05) (S: 2 Hz: -26 +/- 7.1%; 20 Hz: -26.9 +/-
      7.3%; 40 Hz: -27.7 +/- 7.0%; M: 2 Hz: -37.4 +/- 8.3%; 20 Hz: -35.9 +/- 7.4%; 40
      Hz: -38.2 +/- 9.4%; H: 2 Hz: -46.9 +/- 7.8%; 20 Hz: -48.5 +/- 7.2%; 40 Hz: -51.2
      +/- 7.3%). O2(-) scavenging did not alter (P > 0.05) the vasoconstrictor response
      in S rats (S: 2 Hz: -23.9 +/- 7.6%; 20 Hz: -26.1 +/- 9.1%; 40 Hz: -27.5 +/-
      7.2%), whereas the response in ET rats was diminished (M: 2 Hz: -26.3 +/- 5.1%;
      20 Hz: -28.7 +/- 5.3%; 40 Hz: -28.5 +/- 5.6%; H: 2 Hz: -35.5 +/- 10.3%; 20 Hz: 
      38.6 +/- 6.8%; 40 Hz: -43.9 +/- 5.9%, P < 0.05). TIRON + N(omega)-nitro-l
      arginine methyl ester increased vasoconstrictor responsiveness (P < 0.05) in ET
      rats (M: 2 Hz: -47.7 +/- 9.8%; 20 Hz: -41.2 +/- 7.2%; 40 Hz: -50.5 +/- 7.9%; H: 2
      Hz: -55.8 +/- 7.6%; 20 Hz: -55.7 +/- 7.8%; 40 Hz: -58.7 +/- 6.2%), whereas, in S
      rats, the response was unchanged (2 Hz: -29.4 +/- 8.7%; 20 Hz: -30.0 +/- 7.4%; 40
      Hz: -35.2 +/- 10.3%; P > 0.05). These data indicate that the augmented
      sympathetic vasoconstrictor responsiveness in ET rats was related to increased
      oxidative stress and altered nitric oxide-mediated inhibition of
      vasoconstriction.

PMID- 23558387
TI  - TNF signals via neuronal-type nitric oxide synthase and reactive oxygen species
      to depress specific force of skeletal muscle.
AB  - TNF promotes skeletal muscle weakness, in part, by depressing specific force of
      muscle fibers. This is a rapid, receptor-mediated response, in which TNF
      stimulates cellular oxidant production, causing myofilament dysfunction. The
      oxidants appear to include nitric oxide (NO); otherwise, the redox mechanisms
      that underlie this response remain undefined. The current study tested the
      hypotheses that 1) TNF signals via neuronal-type NO synthase (nNOS) to depress
      specific force, and 2) muscle-derived reactive oxygen species (ROS) are essential
      co-mediators of this response. Mouse diaphragm fiber bundles were studied using
      live cell assays. TNF exposure increased general oxidant activity (P < 0.05;
      2',7'-dichlorodihydrofluorescein diacetate assay) and NO activity (P < 0.05; 4
      amino-5-methylamino-2',7'-difluorofluorescein diacetate assay) and depressed
      specific force across the full range of stimulus frequencies (1-300 Hz; P <
      0.05). These responses were abolished by pretreatment with N(omega)-nitro-L
      arginine methyl ester (L-NAME; a nonspecific inhibitor of NOS activity),
      confirming NO involvement. Genetic nNOS deficiency replicated L-NAME effects on
      TNF-treated muscle, diminishing NO activity (-80%; P < 0.05) and preventing the
      decrement in specific force (P < 0.05). Comparable protection was achieved by
      selective depletion of muscle-derived ROS. Pretreatment with either SOD (degrades
      superoxide anion) or catalase (degrades hydrogen peroxide) depressed oxidant
      activity in TNF-treated muscle and abolished the decrement in specific force.
      These findings indicate that TNF signals via nNOS to depress contractile
      function, a response that requires ROS and NO as obligate co-mediators.

PMID- 23558388
TI  - Elastase-coupled beads as a tool for characterizing localized alveolar tissue
      destruction associated with the onset of emphysema.
AB  - Intratracheal elastase challenge of laboratory animals has long been established
      as a model for observing the physiological and morphological changes that result
      from alveolar destruction, the hallmark of emphysema. However, instillation of
      elastase suspended in buffer results in widespread inflammation and variable
      emphysematous lesions, which has made the identification of specific cellular and
      molecular events associated with the onset of emphysema difficult to define. Here
      we establish a bead-based elastase delivery system that induces localized tissue
      destruction, a key event in the initiation of emphysema. Elastase was coupled to
      bisacrylamide beads, which were shown to retain enzymatic activity prior to
      intratracheal administration in mice. C57BL/6 mice were given a single dose of
      40,000 beads, which became distributed throughout the small airways and
      parenchyma of the lung. Elastase-coupled beads resulted in a quantifiable loss of
      alveolar tissue immediately surrounding the beads, an effect that was not
      observed with beads that lacked protein altogether or with beads containing
      elastase inactivated by an irreversible inhibitor. Furthermore, beads bound with
      active elastase elicited local recruitment of mononuclear cells, including
      macrophages, and polymorphonuclear neutrophils to the site of bead deposition, a
      feature consistent with the cellular infiltration observed following conventional
      solubilized elastase challenges. This work identifies a novel bead-based enzyme
      delivery system that also extends the elastase model of emphysema to permit the
      characterization of mechanisms that drive alveolar surface area loss following
      elastin degradation in focal emphysematous lesions.

PMID- 23558389
TI  - Lactate kinetics at the lactate threshold in trained and untrained men.
AB  - To understand the meaning of the lactate threshold (LT) and to test the
      hypothesis that endurance training augments lactate kinetics [i.e., rates of
      appearance and disposal (Ra and Rd, respectively, mg.kg(-1).min(-1)) and
      metabolic clearance rate (MCR, ml.kg(-1).min(-1))], we studied six untrained (UT)
      and six trained (T) subjects during 60-min exercise bouts at power outputs (PO)
      eliciting the LT. Trained subjects performed two additional exercise bouts at a
      PO 10% lower (LT-10%), one of which involved a lactate clamp (LC) to match blood
      lactate concentration ([lactate]b) to that achieved during the LT trial. At LT,
      lactate Ra was higher in T (24.1 +/- 2.7) than in UT (14.6 +/- 2.4; P < 0.05)
      subjects, but Ra was not different between UT and T when relative exercise
      intensities were matched (UT-LT vs. T-LT-10%, 67% Vo2max). At LT, MCR in T (62.5
      +/- 5.0) subjects was 34% higher than in UT (46.5 +/- 7.0; P < 0.05), and a
      reduction in PO resulted in a significant increase in MCR by 46% (LT-10%, 91.5 +/
      14.9, P < 0.05). At matched relative exercise intensities (67% Vo2max), MCR in T
      subjects was 97% higher than in UT (P < 0.05). During the LC trial, MCR in T
      subjects was 64% higher than in UT (P < 0.05), in whom %Vo2max and [lactate]b
      were similar. We conclude that 1) lactate MCR reaches an apex below the LT, 2) LT
      corresponds to a limitation in MCR, and 3) endurance training augments capacities
      for lactate production, disposal and clearance.

PMID- 23558390
TI  - Expiratory muscle fatigue does not regulate operating lung volumes during high
      intensity exercise in healthy humans.
AB  - To determine whether expiratory muscle fatigue (EMF) is involved in regulating
      operating lung volumes during exercise, nine recreationally active subjects
      cycled at 90% of peak work rate to the limit of tolerance with prior induction of
      EMF (EMF-ex) and for a time equal to that achieved in EMF-ex without prior
      induction of EMF (ISO-ex). EMF was assessed by measuring changes in magnetically
      evoked gastric twitch pressure. Changes in end-expiratory and end-inspiratory
      lung volume (EELV and EILV) and the degree of expiratory flow limitation (EFL)
      were quantified using maximal expiratory flow-volume curves and inspiratory
      capacity maneuvers. Resistive breathing reduced gastric twitch pressure (-24 +/-
      14%, P = 0.004). During EMF-ex, EELV decreased from rest to the 3rd min of
      exercise [39 +/- 8 vs. 27 +/- 7% of forced vital capacity (FVC), P = 0.001]
      before increasing toward baseline (34 +/- 8% of FVC end exercise, P = 0.073 vs.
      rest). EILV increased from rest to the 3rd min of exercise (54 +/- 8 vs. 84 +/-
      9% of FVC, P = 0.006) and remained elevated to end exercise (88 +/- 9% of FVC).
      Neither EELV (P = 0.18) nor EILV (P = 0.26) was different at any time point
      during EMF-ex vs. ISO-ex. Four subjects became expiratory flow limited during the
      final minute of EMF-ex and ISO-ex; the degree of EFL was not different between
      trials (37 +/- 18 vs. 35 +/- 16% of tidal volume, P = 0.38). At end exercise in
      both trials, EELV was greater in subjects without vs. subjects with EFL. These
      findings suggest that 1) contractile fatigue of the expiratory muscles in healthy
      humans does not regulate operating lung volumes during high-intensity sustained
      cycle exercise; and 2) factors other than "frank" EFL cause the terminal increase
      in EELV.

PMID- 23558391
TI  - Time- and age-dependent effects of serotonin on gasping and autoresuscitation in
      neonatal mice.
AB  - The role of brain stem serotonin (5-hydroxytryptamine, 5-HT) in autoresuscitation
      in neonatal life is unclear. We hypothesized that a specific loss of 5-HT would
      compromise gasping and autoresuscitation mainly in the second postnatal week and
      that acute restoration of 5-HT would reverse the defects. We exposed postnatal
      day (P)4-5, P8-9, and P11-12 tryptophan-hydroxylase-2 knockout (TPH2(-/-)) and
      wild-type littermates (WT) to 10 episodes of anoxia (97% N2, 3% CO2), measuring
      survival, gasp latency, gasp frequency (fB), and the time required to restore
      eupnea and heart rate. We also tested P8-9 TPH2(-/-) mice after restoring 5-HT
      with a single injection of 5-hydroxytryptophan (5-HTP) 1-2 h before testing or
      with multiple injections beginning 24 h before testing. At P4-5 and P8-9, but not
      at P11-12, gasp latency and the recovery of eupnea were delayed ~2- to 3-fold in
      TPH2(-/-) pups compared with WT (P < 0.001). At all ages, TPH2(-/-) pups
      displayed reduced gasp fB (~20-30%; P < 0.001) and delayed heart rate recovery
      (~60%; P = 0.002) compared with WT littermates. TPH2(-/-) survival was reduced
      compared with WT (P < 0.001), especially at P8-9 and P11-12 (P = 0.004). Whereas
      1-2 h of 5-HTP treatment improved the gasp latency and fB of P8-9 TPH2(-/-) pups,
      improved cardiorespiratory recovery and survival required 24 h of treatment. Our
      data suggest that 5-HT operates over a long time span (24 h) to improve survival
      during episodic severe hypoxia. Early in development (P4-9), 5-HT is critical for
      both respiratory and cardiovascular components of autoresuscitation; later (P11
      12), it is critical mainly for cardiovascular components. Nevertheless, the
      effect of 5-HT deficiency on survival is most striking from P8 to P12.

PMID- 23558392
TI  - Muscle fascicle strains in human gastrocnemius during backward downhill walking.
AB  - Extensive muscle damage can be induced in isolated muscle preparations by
      performing a small number of stretches during muscle activation. While typically
      these fiber strains are large and occur over long lengths, the extent of exercise
      induced muscle damage (EIMD) observed in humans is normally less even when
      multiple high-force lengthening actions are performed. This apparent discrepancy
      may be due to differences in muscle fiber and tendon dynamics in vivo; however,
      muscle and tendon strains have not been quantified during muscle-damaging
      exercise in humans. Ultrasound and an infrared motion analysis system were used
      to measure medial gastrocnemius fascicle length and lower limb kinematics while
      humans walked backward, downhill for 1 h (inducing muscle damage), and while they
      walked briefly forward on the flat (inducing no damage). Supramaximal tibial
      nerve stimulation, ultrasound, and an isokinetic dynamometer were used to
      quantify the fascicle length-torque relationship pre- and 2 h postexercise.
      Torque decreased ~23%, and optimal fascicle length shifted rightward ~10%,
      indicating that EIMD occurred during the damage protocol even though medial
      gastrocnemius fascicle stretch amplitude was relatively small (~18% of optimal
      fascicle length) and occurred predominantly within the ascending limb and plateau
      region of the length-torque curve. Furthermore, tendon contribution to overall
      muscle-tendon unit stretch was ~91%. The data suggest the compliant tendon plays
      a role in attenuating muscle fascicle strain during backward walking in humans,
      thus minimizing the extent of EIMD. As such, in situ or in vitro mechanisms of
      muscle damage may not be applicable to EIMD of the human gastrocnemius muscle.

PMID- 23558393
TI  - Mechanical strain and airway responsiveness: how long does it take, how long will
      it last?

PMID- 23558395
TI  - Is ultrasound training in specialized qualified prenatal diagnosis in German
      speaking countries still sufficient?

PMID- 23558394
TI  - Increase in work productivity of depressed individuals with improvement in
      depressive symptom severity.
AB  - OBJECTIVE: The authors sought to identify baseline clinical and sociodemographic
      characteristics associated with work productivity in depressed outpatients and to
      assess the effect of treatment on work productivity. METHOD: Employed depressed
      outpatients 18-75 years old who completed the Work Productivity and Activity
      Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the
      Sequenced Treatment Alternatives to Relieve Depression study. For patients who
      did not remit after an initial adequate antidepressant trial (level 1), either a
      switch to sertraline, sustained-release bupropion, or extended-release
      venlafaxine or an augmentation with sustained-release bupropion or buspirone was
      provided (level 2). Participants' clinical and demographic characteristics and
      treatment outcomes were analyzed for associations with baseline work productivity
      and change in productivity over time. RESULTS: Education, baseline depression
      severity, and melancholic, atypical, and recurrent depression subtypes were all
      independently associated with lower benefit to work productivity domains. During
      level 1 treatment, work productivity in several domains improved with reductions
      in depressive symptom severity. However, these findings did not hold true for
      level 2 outcomes; there was no significant association between treatment response
      and reduction in work impairment. Results were largely confirmed when multiple
      imputations were employed to address missing data. During this additional
      analysis, an association was also observed between greater impairment in work
      productivity and higher levels of anxious depression. CONCLUSIONS: Patients with
      clinically significant reductions in symptom severity during initial treatment
      were more likely than nonresponders to experience significant improvements in
      work productivity. In contrast, patients who achieved symptom remission in second
      step treatment continued to have impairment at work. Patients who have
      demonstrated some degree of treatment resistance are more prone to persistent
      impairment in occupational productivity, implying a need for additional, possibly
      novel, treatments.

PMID- 23558396
TI  - [Diagnosis and therapy of fetal arrhythmias 1 - Methods of rhythm diagnosis,
      extrasystole and bradyarrhythias].

PMID- 23558397
TI  - EFSUMB guidelines and recommendations on the clinical use of ultrasound
      elastography. Part 1: Basic principles and technology.
AB  - The technical part of these Guidelines and Recommendations, produced under the
      auspices of EFSUMB, provides an introduction to the physical principles and
      technology on which all forms of current commercially available ultrasound
      elastography are based. A difference in shear modulus is the common underlying
      physical mechanism that provides tissue contrast in all elastograms. The
      relationship between the alternative technologies is considered in terms of the
      method used to take advantage of this. The practical advantages and disadvantages
      associated with each of the techniques are described, and guidance is provided on
      optimisation of scanning technique, image display, image interpretation and some
      of the known image artefacts.

PMID- 23558398
TI  - How perfect are you with defective probes? Information on the results of the mini
      trial on technical quality assurance during the "Ultraschall 2012" conference in
      Davos.
AB  - This article deals with the technical quality assurance of ultrasound B-systems.
      As part of a mini-trial during the Dreilandertreffen in Davos "Ultrasound 2012",
      we addressed the question as to whether physicians can detect faulty probes
      spontaneously during live scanning B-mode. For this purpose a special diagnostic
      device had been prepared so that groups of piezoelectric elements in the array
      were without function. Then the images had to be characterized by test persons
      without knowledge of the faulty elements. The results show that a deterioration
      of the image could be detected starting at five disabled elements. Due to the
      small number of test persons, our statements are only preliminary.

PMID- 23558400
TI  - A facile synthesis of strong near infrared fluorescent layered double hydroxide
      nanovehicles with an anticancer drug for tumor optical imaging and therapy.
AB  - In this work, a new multifunctional nanovehicle for tumor optical imaging and
      therapy was developed using Y2O3:Er(3+),Yb(3+) nanoparticles as near infrared
      fluorescent nanophosphors, and MgAl-layered double hydroxide (LDH) nanosheets as
      anticancer drug nanovehicles. Monodispersed Y2O3:Er(3+),Yb(3+) nanophosphors were
      readily synthesized by the urea assisted homogenous precipitation method.
      Hierarchically structured LDH nanosheets intercalated with an anticancer drug,
      fluorouracil (5FU), were deposited on the surface of Y2O3:Er(3+),Yb(3+)@SiO2 by a
      simple precipitation method followed by hydrothermal treatment. The resultant
      Y2O3:Er(3+),Yb(3+)@SiO2@LDH-5FU nanovehicles exhibit strong red upconversion
      fluorescence under the excitation of a 980 nm laser, which allows tracking of the
      nanovehicles after localization in cancer cells. A better anticancer efficiency
      was obtained over the nanovehicles than the free drug which can be attributed to
      their positively charged surfaces for favorable interaction with the negatively
      charged cell membranes. The multifunctional nanovehicles designed in this work
      are expected to be promising material candidates for simultaneous tumor optical
      imaging and therapy.

PMID- 23558399
TI  - On-chip biomedical imaging.
AB  - Lab-on-a-chip systems have been rapidly emerging to pave the way toward ultra
      compact, efficient, mass producible and cost-effective biomedical research and
      diagnostic tools. Although such microfluidic and microelectromechanical systems
      have achieved high levels of integration, and are capable of performing various
      important tasks on the same chip, such as cell culturing, sorting and staining,
      they still rely on conventional microscopes for their imaging needs. Recently,
      several alternative on-chip optical imaging techniques have been introduced,
      which have the potential to substitute conventional microscopes for various lab
      on-a-chip applications. Here we present a critical review of these recently
      emerging on-chip biomedical imaging modalities, including contact shadow imaging,
      lens-free holographic microscopy, fluorescent on-chip microscopy and lens-free
      optical tomography.

PMID- 23558401
TI  - Predicting disease progression after regional therapy for in-transit melanoma.
AB  - IMPORTANCE: Although approximately 30% to 50% of patients experience a complete
      response after regional chemotherapy for in-transit melanoma, a subset of
      patients will develop rapidly progressive disease. In the current era of an
      expanding armamentarium, including both regional and systemic options for
      treating advanced melanoma, identifying perioperative factors that predict
      disease progression may obviate unnecessary morbidity associated with regional
      therapy and avoid delays in systemic therapy. OBJECTIVE: To identify patient
      related clinical and pathological variables, as well as procedural factors, that
      correlate with disease progression. DESIGN: Using a prospectively maintained
      database, we identified patients who either underwent first-time melphalan-based
      isolated limb infusion (ILI) or first-time hyperthermic isolated limb perfusion
      (HILP) for in-transit melanoma. Response was defined using modified Response
      Evaluation Criteria in Solid Tumors for cutaneous disease at 3 months after
      treatment. Survival analyses were performed using the Kaplan-Meier method, with
      the differences in survival curves compared using a log-rank test. Potential
      preoperative and procedural predictors of in-field progressive disease were
      analyzed using logistic regression. PARTICIPANTS: Of the 258 patients included in
      the database, 215 were identified as having undergone first-time regional
      therapy. Of these 215 patients, 134 underwent ILI, and 81 underwent HILP.
      EXPOSURE: Regional therapy (ILI or HILP). MAIN OUTCOMES AND MEASURES: Complete
      response or progressive disease. RESULTS: Of 134 patients who underwent ILI, 43
      (32.1%) experienced in-field progressive disease. Of 81 patients who underwent
      HILP, 9 (11.1%) experienced in-field progressive disease. The median survival for
      patients with in-field progressive disease was 20.3 months for the ILI cohort and
      15.0 months for the HILP cohort. In general, patients with progressive disease
      were younger, with advanced-stage melanoma and increased tumor burden. Compared
      with patients who experienced a complete response, patients with in-field
      progressive disease after ILI were younger (odds ratio, 1.06 [95% CI, 0.90-0.98];
      P = .002). For patients who underwent HILP, no clinically relevant preoperative
      predictors of in-field progressive disease were identified. Procedural variables,
      including chemotherapeutic dosing, degree of acidosis or base deficit achieved,
      and peak temperature attained, were not predictors of in-field progressive
      disease after ILI or HILP. CONCLUSIONS AND RELEVANCE: Patient, clinical, and
      procedural factors are unreliable predictors of in-field progressive disease
      after regional therapy in patients with in-transit melanoma. Defining the
      potential utility of molecular markers in predicting response or failure of
      regional therapy should be the focus of future research efforts.

PMID- 23558402
TI  - Limb fitting for quadruple amputees: report of two cases of symmetrical
      peripheral gangrene caused by pneumococcal purpura fulminans.
AB  - BACKGROUND: We report our experiences of prosthetic fitting in quadruple
      amputees. Two patients underwent quadruple amputation after suffering from
      disseminated intravascular coagulation in conjunction with pneumococcemia with
      purpura fulminans. CASE DESCRIPTION AND METHODS: The first patient, a 52-year-old
      man, underwent bilateral transradial, left transtibial, and right transfemoral
      amputation, and the second patient, a 62-year-old man, underwent bilateral
      transradial and bilateral transfemoral amputation, both for symmetrical
      peripheral gangrene subsequent to septic shock. FINDINGS AND OUTCOMES: The
      amputations were accompanied by skin damage due to ischemic tissue changes both
      on the stumps and on the nose and/or lips. The combination of the intensive
      prosthetic rehabilitation program and supportive medical care led to completely
      independent functioning, including driving a car, with the use of four prosthetic
      limbs and a wheelchair in both cases. CONCLUSION: Early initiation of a
      multidisciplinary approach can properly address impairments and minimize future
      disability.

PMID- 23558403
TI  - Autophagy has a significant role in determining skin color by regulating
      melanosome degradation in keratinocytes.
AB  - Melanin in the epidermis determines the wide variation in skin color associated
      with ethnic skin diversity. Ethnic differences exist regarding melanosome loss in
      keratinocytes, but the mechanisms underlying these differences, and their
      contribution to the regulation of skin color, remain unclear. Here, we explored
      the involvement of autophagy in determining skin color by regulating melanosome
      degradation in keratinocytes. Keratinocytes derived from Caucasian skin exhibit
      higher autophagic activity than those derived from African American (AA) skin.
      Furthermore, along with the higher autophagy activity in Caucasian skin-derived
      keratinocytes compared with AA skin-derived keratinocytes, Caucasian skin-derived
      keratinocytes were more sensitive to melanosome treatment as shown by their
      enhanced autophagic activity, which may reflect the substantial mechanisms in the
      human epidermis owing to the limitations of the models. Melanosome accumulation
      in keratinocytes was accelerated by treatment with lysosomal inhibitors or with
      small interfering RNAs specific for autophagy-related proteins, which are
      essential for autophagy. Furthermore, consistent with the alterations in skin
      appearance, the melanin levels in human skin cultured ex vivo and in human skin
      substitutes in vitro were substantially diminished by activators of autophagy and
      enhanced by the inhibitors. Taken together, our data reveal that autophagy has a
      pivotal role in skin color determination by regulating melanosome degradation in
      keratinocytes, and thereby contributes to the ethnic diversity of skin color. 

PMID- 23558404
TI  - Overexpression of the gastrin-releasing peptide in cutaneous nerve fibers and its
      receptor in the spinal cord in primates with chronic itch.

PMID- 23558406
TI  - A parabolic model to control quantum interference in T-shaped molecular
      junctions.
AB  - Quantum interference (QI) effects in molecular devices have drawn increasing
      attention over the past years due to their unique features observed in the
      conductance spectrum. For the further development of single molecular devices
      exploiting QI effects, it is of great theoretical and practical interest to
      develop simple methods controlling the emergence and the positions of QI effects
      like anti-resonances or Fano line shapes in conductance spectra. In this work,
      starting from a well-known generic molecular junction with a side group (T-shaped
      molecule), we propose a simple graphical method to visualize the conditions for
      the appearance of quantum interference, Fano resonances or anti-resonances, in
      the conductance spectrum. By introducing a simple graphical representation
      (parabolic diagram), we can easily visualize the relation between the electronic
      parameters and the positions of normal resonant peaks and anti-resonant peaks
      induced by quantum interference in the conductance spectrum. This parabolic model
      not only can predict the emergence and energetic position of quantum interference
      from a few electronic parameters but also can enable one to know the coupling
      between the side group and the main conduction channel from measurements in the
      case of orthogonal basis. The results obtained within the parabolic model are
      validated using density-functional based quantum transport calculations in
      realistic T-shaped molecular junctions. 

PMID- 23558407
TI  - Roche offers researchers access to all Tamiflu trials.

PMID- 23558405
TI  - Perivascular hair follicle stem cells associate with a venule annulus.
AB  - The perivascular microenvironment helps in maintaining stem cells in many
      tissues. We sought to determine whether there is a perivascular niche for hair
      follicle stem cells. The association of vessels and follicle progenitor cells
      began by embryonic day 14.5, when nascent hair placodes had blood vessels
      approaching them. By birth, a vascular annulus stereotypically surrounded the
      keratin 15 negative (K15-) stem cells in the upper bulge and remained associated
      with the K15- upper bulge throughout the hair cycle. The angiogenic factor Egfl6
      was expressed by the K15- bulge and was localized adjacent to the vascular
      annulus, which comprised post-capillary venules. Although denervation altered the
      phenotype of upper bulge stem cells, the vascular annulus persisted in surgically
      denervated mouse skin. The importance of the perivascular niche was further
      suggested by the fact that vascular annuli formed around the upper bulge of de
      novo-reconstituted hair follicles before their innervation. Together, these
      findings demonstrate that the upper bulge is associated with a perivascular niche
      during the establishment and maintenance of this specialized region of hair
      follicle stem cells. 

PMID- 23558409
TI  - Obstructive sleep apnea syndrome and its association with vitamin D deficiency.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a widespread disorder
      characterized by recurrent, partial or complete episodes of apnea due to upper
      airway tract obstruction during sleeping period. Deficiency of vitamin D has
      roles in development of many diseases. Association between presence and severity
      of OSAS and vitamin D has recently gained research interest. AIM: The aim of our
      study was to investigate the association between serum 25-hydroxy [25 (OH)]
      vitamin D levels and severity of disease in patients with OSAS. MATERIAL AND
      METHODS: One hundred and fifty OSAS patients (50 patients with mild, 50 with
      moderate, 50 with severe OSAS) who were diagnosed by polysomnography (PSG) and 32
      non-OSAS controls who were referred to the Health Ministry Ankara Numune Training
      and Research Hospital, Endocrinology and Metabolism Department, from January 2010
      to May 2011 were included in the study. Serum 25(OH)D, PTH, calcium and
      phosphorus levels were evaluated in all the patients who were recruited to the
      study. RESULTS: There was no statistically significant difference in serum
      25(OH)D levels between OSAS and controls (p>0.05). However, in subgroup analysis
      of OSAS, we found that the patients with severe OSAS had significantly lower
      levels of 25(OH)D as compared with other groups (p=0.003). Also, the number of
      patients with serum 25(OH)D deficiency (<10 MUg/dl) were higher in OSAS group
      than in controls (p<0.05). CONCLUSIONS: We found that when the severity of OSAS
      increases, 25(OH)D deficiency becomes more pronounced.

PMID- 23558408
TI  - The relation between cancer patient treatment decision-making roles and quality
      of life.
AB  - BACKGROUND: The objective of this study was to explore relations between patient
      role preferences during the cancer treatment decision-making process and quality
      of life (QOL). METHODS: One-year cancer survivors completed a survey in 2000 as
      part of a larger survey conducted by the American Cancer Society. The current
      report was based on survey respondents from Minnesota (response rate, 37.4%).
      Standardized measures included the Profile of Mood States (scores were converted
      to have a range, from 0 to 100, with 100 indicating the best mood), the Medical
      Outcomes Survey 36-item short-form health survey (SF-36) (standardized scores),
      and the Control Preferences Scale. Patients' actual and preferred role preference
      distributions and concordance between roles were compared with QOL scores using 2
      sample t test methodology. RESULTS: The actual role of survivors (n = 594) in
      cancer care was 33% active, 50% collaborative, and 17% passive. Their preferred
      role was 35% active, 53% collaborative, and 13% passive. Overall, 88% of
      survivors had concordant preferred and actual roles. Survivors who had concordant
      roles had higher SF-36 Physical Component Scale (PCS) scores (P < .01), higher
      vitality (P = .01), less fatigue (P < .01), less confusion (P = .01), less anger
      (P = .046), and better overall mood (P = .01). These results were similar among
      both women and younger individuals (aged <60 years). Survivors who had active
      actual roles had higher PCS scores (P < .01), less tension (P = .04), and higher
      vitality (P = .04) than survivors who were either collaborative or passive. No
      differences existed in QOL scores according to preferred role. CONCLUSIONS:
      Survivors who experienced discordance between their actual role and their
      preferred role reported substantial QOL deficits in both physical and emotional
      domains. These results indicate the need to support patient preferences.

PMID- 23558410
TI  - Selective area growth of In(Ga)N/GaN nanocolumns by molecular beam epitaxy on GaN
      buffered Si(111): from ultraviolet to infrared emission.
AB  - Selective area growth of In(Ga)N/GaN nanocolumns was performed on GaN-buffered
      Si(111) substrates by plasma-assisted molecular beam epitaxy. Undoped and Si
      doped GaN buffer layers were first grown on Si(111) substrates, showing
      photoluminescence excitonic emission without traces of other low energy
      contributions, in particular, the yellow band. The GaN buffer surface roughness
      (between 10 and 14 nm, the rms value in a 10 * 10 MUm(2) area) was low enough to
      allow the fabrication of a thin (7 nm thick) well defined Ti nanohole mask, for
      the selective area growth. Ordered In(Ga)N/GaN nanocolumns emitting from the
      ultraviolet (3.2 eV) to the infrared (0.78 eV) were obtained. The morphology and
      the emission efficiency of the In(Ga)N/GaN nanocolumns emitting at a given
      wavelength could be substantially improved by tuning the In/Ga and total III/N
      ratios. An estimated internal quantum efficiency of 36% was derived from
      photoluminescence data for green emitting nanocolumns.

PMID- 23558411
TI  - Endocrinology in crisis?

PMID- 23558413
TI  - Commentary on "healthcare access and disparities in chronic medical conditions in
      urban populations".

PMID- 23558412
TI  - Healthcare access and disparities in chronic medical conditions in urban
      populations.
AB  - OBJECTIVES: The purpose of this study was to identify barriers and disparities in
      healthcare access and the factors associated with them in an urban population.
      METHODS: Eligible patients were consented and enrolled randomly from the
      inpatient internal medicine unit at Truman Medical Center, Kansas City, Missouri,
      a 250-bed hospital recognized for its broad range of acute and chronic diseases
      seen in its inpatient and outpatient care. They had one or more of the following
      chronic medical conditions (CMCs): congestive heart failure, chronic obstructive
      pulmonary disease, diabetes mellitus, hypertension, chest pain, or cirrhosis. One
      hundred patients were interviewed regarding challenges they have encountered as
      consumers and their understanding of CMCs. RESULTS: Interview results indicate
      patients' understanding of their CMC, the associated needs for self-management,
      and the potential health consequences are contributing factors leading to
      repeated visits to the emergency department. CONCLUSIONS: Our study suggests that
      access to the following health-focused services has the potential to reduce the
      rate of emergency department visits and hospitalizations, morbidity, mortality,
      and the burden of cost. These services include adequate access to and utilization
      of primary care characterized by preventive care, early detection of acute
      illness, ongoing chronic disease management through easy access to primary
      providers, and adequate health literacy about CMC.

PMID- 23558414
TI  - Time to linkage to care and viro-immunologic parameters of individuals diagnosed
      before and after the 2006 HIV testing recommendations.
AB  - OBJECTIVES: To assess the time from linkage to care and viro-immunologic
      parameters before and after implementation of the Centers for Disease Control and
      Prevention's 2006 revised human immunodeficiency virus (HIV) testing strategy.
      METHODS: Case reports from South Carolina's enhanced HIV/AIDS (acquired
      immunodeficiency syndrome) Reporting System were used to compare time to linkage
      to care and viro-immunologic indicators at diagnosis and 1 year after diagnosis
      of HIV in individuals diagnosed between 2004 and 2006 (n = 2456) with those
      diagnosed between 2008 and 2010 (n = 2118). CD4 T-cell count/percent and viral
      load tests were used as a proxy for a clinical visit and to determine disease
      stage. RESULTS: Individuals diagnosed between 2008 and 2010 were less likely than
      those diagnosed between 2004 and 2006 to be in care after 12 months than within 3
      months of HIV diagnosis (adjusted odds ratio [AOR] 0.42, 95% confidence interval
      [CI] 0.34-0.51). Individuals diagnosed between 2008 and 2010 were more likely
      than those diagnosed between 2004 and 2006 to have high CD4 T-cell counts (>500
      cells per cubic millimeter than <=200 cells per cubic millimeter; AOR 1.24, 95%
      CI 1.01-1.51) and have undetectable viral loads 1 year post-HIV diagnosis (AOR
      8.42, 95% CI 6.96-10.18). Although period of diagnosis did not predict disease
      stage 1 year post-HIV diagnosis (AOR 0.99, 95% CI 0.87-1.13), there was a
      decrease from 13% between 2004 and 2006 to 10% between 2008 and 2010 in the
      percentage of HIV-only patients at diagnosis who progressed to AIDS 1 year post
      HIV diagnosis. CONCLUSIONS: Implementation of routine, opt-out HIV testing
      resulted in more timely linkage to care and improved viro-immunologic parameters
      1 year postdiagnosis when compared with the previous testing recommendations.

PMID- 23558415
TI  - Lack of preoperative predictors of the immediate return of postoperative bladder
      emptying after uterosacral ligament suspension.
AB  - OBJECTIVES: To determine whether preoperative postvoid residual volume (PVR),
      pelvic organ prolapse quantification (POPQ) stage, patient characteristics, or
      concurrent operations are predictors of immediate postoperative bladder emptying
      after uterosacral ligament suspension (USLS). METHODS: A review of patients
      undergoing USLS in 2008 and 2009 was performed. The factors analyzed included
      patient age, body mass index, parity, preoperative PVR, POPQ stage, concurrent
      anterior repair, posterior repair, hysterectomy and/or sling procedures, and
      postoperative voiding trial status. RESULTS: During the study interval, 151
      patients underwent USLS with various combinations of concurrent procedures. The
      mean preoperative PVR was 90 mL. Seventy-five patients (50%) passed the
      postoperative voiding trial on postoperative day 1. Patients who passed the
      postoperative voiding trial and those who failed had similar average preoperative
      PVR (P = 0.94), similar age (P = 0.14), body mass index (P = 0.45), parity (P =
      0.82), and preoperative POPQ stage (P = 0.80). There was no difference (P >=
      0.14) among concurrent surgical procedures in the proportion of patients who
      passed the postoperative voiding trial based on univariate analyses. CONCLUSIONS:
      In our cohort of patients, preoperative PVR, POPQ stage, and other patient
      characteristics were not predictors of immediate postoperative bladder emptying
      after USLS. Postoperative voiding function is one of the most unpredictable
      aspects of pelvic reconstructive surgery.

PMID- 23558416
TI  - Four-year trends of inappropriate proton pump inhibitor use after hospital
      discharge.
AB  - BACKGROUND: Several hospital-based studies have determined that physicians often
      inappropriately prescribe acid-suppressive medications for stress ulcer
      prevention in hospitalized patients and continue these drugs after discharge. We
      sought to determine the frequency of inappropriate proton pump inhibitor (PPI)
      use continued at discharge within our geographic region. METHODS: We undertook a
      retrospective review of the medical records and pharmacy prescription database of
      a large regional insurance carrier from January 2005 through December 2008 (total
      hospital admissions 96,669). The primary inclusion criterion was hospital
      initiated PPI therapy and continuation on hospital discharge without an
      appropriate indication. Patients receiving a PPI at the time of admission were
      excluded from the analysis. RESULTS: The number of patients per year discharged
      on a PPI decreased during the study period: 876 (2005), 763 (2006), 562 (2007),
      and 485 (2008). Of the patients discharged on a PPI, the number (%) of patients
      receiving PPIs inappropriately were 695 (79%; 2005); 627 (82%; 2006), 441 (78%;
      2007), and 397 (82%; 2008). The annual number of PPI prescriptions and PPI doses
      dispensed decreased from 2015 to 1263 and from 60,608 to 38,742, respectively,
      during the study period. The estimated 4-year cost of inappropriate PPI use was
      $595,809, although cost savings from the absolute reduction in inappropriate PPI
      use over time was $65,598. CONCLUSIONS: We report a significant decrease of 39%
      in the number of inappropriate discharge prescriptions for PPIs during the study
      period; however, the percentage of inappropriate use of PPIs remains high. There
      is room for improvement in cost-effective use of PPIs.

PMID- 23558417
TI  - Parental perspectives of diabetes management in Alabama public schools.
AB  - OBJECTIVES: The purpose of this study was to assess parental perceptions of the
      current state of care for children with diabetes in the Alabama public school
      system, identify existing disparities, and determine what resources would most
      improve diabetes management in this setting. There is a significant need for such
      information because of the paucity of published data on the current state of
      diabetes care in Alabama public schools. METHODS: We based our survey on the
      American Diabetes Association guidelines and collected responses on the Internet
      via SurveyMonkey and by paper surveys. We distributed surveys to parents of
      children with diabetes through the Children's Hospital endocrinology clinic, a
      diabetes camp, and through the Alabama Association of School Nurses e-mail
      listserv. RESULTS: A majority of children had type 1 diabetes mellitus. Students
      who could conveniently check their blood glucose levels (BGLs) at school were
      significantly more likely to participate in all school activities and their
      parents were significantly more likely to be satisfied with their child's
      diabetes care at school. Compared with minority students (defined as all races
      other than white), white students were more likely to be able to conveniently
      check their BGLs at school. CONCLUSIONS: The accommodation and care for children
      with diabetes is highly variable within much of the Alabama public school system.
      The ability to conveniently check BGLs at school is key for participation in all
      school activities and for parental satisfaction with diabetes care at school.
      Institution of a uniform, statewide diabetes training protocol for school
      personnel could improve care and parental satisfaction.

PMID- 23558418
TI  - Role of anxiety in the comfort of nonsedated average-risk screening
      sigmoidoscopy.
AB  - OBJECTIVES: The aim of this prospective study was to assess the role of
      generalized anxiety disorder in the comfort of nonsedated, average-risk screening
      sigmoidoscopy. METHODS: Patients were asked to complete a screening questionnaire
      before undergoing average-risk colon cancer screening with nonsedated
      sigmoidoscopy. The questionnaire included demographic information and a series of
      Likert-based and visual analog scales designed to assess patient comfort,
      procedural symptom severity, and satisfaction. The Primary Care Evaluation of
      Mental Disorders questionnaire was used to assess for generalized anxiety
      disorder. Comfort levels and postprocedural symptom severity were recorded
      immediately after the procedure and 1 week postprocedure. chi and t tests were
      used to analyze the data. RESULTS: Eighty-one patients were enrolled in the
      study. Twenty-seven patients tested positive for anxiety (high anxiety), whereas
      54 tested negative (low anxiety). There were no differences in anxiety according
      to sex (P = 0.53), or age (P = 0.32). There was no difference in reaching the
      splenic flexure between high- and low-anxiety patients (P = 0.15); however,
      pairwise comparisons revealed patients with high anxiety reported significantly
      higher levels of abdominal pain after the procedure (P < 0.01) and still recalled
      higher pain from the procedure 1 week later (P < 0.01) than those patients with
      low anxiety scores. Furthermore, those patients with high anxiety reported
      significantly more procedure-related cramping and bloating both immediately after
      the procedure and again 1 week later (P < 0.01). Finally, patients with high
      anxiety reported the procedure as being more uncomfortable 1 week later, when
      compared with low-anxiety patients (P = 0.01). CONCLUSIONS: The level of anxiety
      correlated directly to pain and discomfort postprocedure and related inversely to
      the level of satisfaction. Better management of anxiety may lead to better
      procedural comfort in nonsedated procedures.

PMID- 23558419
TI  - Patients' short-term knowledge of personal polyp history inadequate despite
      systematic notification of results after polypectomy.
AB  - OBJECTIVES: Patients' memories of personal polyp characteristics have been shown
      to be inadequate when compared with the medical record. An accurate polyp history
      is necessary to adhere to guidelines. We sought to determine whether
      systematically informing patients of the results of their colonoscopy and
      pathology in a multifaceted manner could increase their knowledge of their
      personal polyp history. METHODS: We conducted a prospective pilot study of 240
      consecutive patients undergoing screening colonoscopy with polypectomy by a
      single endoscopist (B.J.H.) at a tertiary care center. All of the patients were
      provided with a verbal report of findings immediately after the procedure, an
      endoscopy report specifying polyp size and number, and a mailed letter specifying
      the pathology results of their polyps. Telephone contact was attempted for all of
      the patients. Patients were asked to recall the size, number, and histology of
      their polyps. RESULTS: One hundred (42%) of the patients completed the telephone
      survey. Forty patients remembered the polyp number; five remembered their polyp
      histology, and one recalled the polyp size. None of the patients recalled all
      three factors, although patients who recalled telling a family member the results
      of the colonoscopy were more likely to recall at least one polyp descriptor
      (relative risk 2.62 [95% confidence interval 1.01-6.83]). No other variables were
      associated with polyp recall. CONCLUSIONS: Patients' knowledge of personal polyp
      characteristics, even after systematic notification, does not seem adequate for
      determining the best guideline-based colonoscopy surveillance interval.
      Discussing results with family members may help.

PMID- 23558420
TI  - Predictive analytics: the fifth clinical element.

PMID- 23558421
TI  - Testosterone and QT interval.

PMID- 23558422
TI  - Authors' response.

PMID- 23558423
TI  - Fill volume as an indicator of surface heterogeneity in glass vials for
      parenteral packaging.
AB  - The chemical durability of glass vials for parenteral packaging is typically
      assessed by completely filling the vial with a medium of interest. This testing
      approach can mask the heterogeneous dissolution behavior of vials produced by
      conversion of glass tubing. In this study, the corrosion behavior of vials
      provided by four suppliers was evaluated as a function of fill volume. Vials were
      filled with incrementally increasing volumes of water for injection (WFI) up to
      near-maximum capacity and then autoclaved. The pH and levels of extracted ions
      were measured. The pH of autoclaved WFI generally increased for low fill volumes
      relative to pure WFI, presumably because of extraction of alkali from the heel
      region. The pH was found to generally decrease with increasing fill volume as the
      concentration of extractables was diluted. Analysis of dissolution profiles
      supports the altered surface chemistry of the heel region relative to the body.
      The results of this study demonstrate the potential limitations of conventional
      hydrolytic resistance tests and the susceptibility of the heel region to aqueous
      corrosion.

PMID- 23558424
TI  - Identification of endogenous reference genes for RT-qPCR analysis of plasma
      microRNAs levels in rats with acetaminophen-induced hepatotoxicity.
AB  - Circulating microRNA (miRNA) expression profiles have been reported to be
      promising biomarkers for drug-induced liver injury in preclinical and clinical
      practice. Proper normalization is critical for accurate miRNAs expression
      analysis. Herein, using SYBR green quantitative real-time PCR (RT-qPCR), we
      evaluated the expression stability of six candidate reference genes including two
      commonly used small RNAs (U6, 5S) and four miRNAs (let-7a, miR-92a, miR-103 and
      miR-16) in plasma of rats with acetaminophen-induced hepatotoxicity. Data were
      analysed using geNorm, Normfinder, BestKeeper and comparative delta-Ct
      statistical models, and the results consistently show that miR-103 is the most
      stably expressed reference gene. Whereas the commonly used housekeeping genes 5S
      or U6 are all not suitable normalizers, because 5S exhibits extensive variability
      in expression and U6 has a low expression level across the plasma samples. Then
      the effect of reference genes on normalization of plasma miR-122 was assessed;
      when normalized to the most stable reference gene there were significant
      differences between the acetaminophen-treated group and the vehicle group.
      However, when the data were normalized to a less stably expressed gene, miR-16, a
      biased result was obtained. Therefore, we recommend that miR-103 as suitable
      reference gene for plasma miRNAs analysis for acetaminophen-induced liver injury.
      Data presented in this paper are crucial to successful biomarker discovery and
      validation for the diagnosis of the early stage of acetaminophen hepatotoxicity.

PMID- 23558425
TI  - Chaotic Boltzmann machines.
AB  - The chaotic Boltzmann machine proposed in this paper is a chaotic pseudo-billiard
      system that works as a Boltzmann machine. Chaotic Boltzmann machines are shown
      numerically to have computing abilities comparable to conventional (stochastic)
      Boltzmann machines. Since no randomness is required, efficient hardware
      implementation is expected. Moreover, the ferromagnetic phase transition of the
      Ising model is shown to be characterised by the largest Lyapunov exponent of the
      proposed system. In general, a method to relate probabilistic models to nonlinear
      dynamics by derandomising Gibbs sampling is presented.

PMID- 23558426
TI  - Encapsulated recyclable porous materials: an effective moisture-triggered
      fragrance release system.
AB  - A moisture-triggered release system was developed using porous metal-organic
      materials as encapsulating agents. Release of both hydrophilic (ethyl butyrate)
      and hydrophobic (D-limonene) fragrance compounds was investigated by gas
      adsorption measurement, thermogravimetric analysis and gas chromatography-mass
      spectroscopy. These materials exhibit exceptional fragrance compatibility and
      controlled release compared to the current leading encapsulation technology.

PMID- 23558427
TI  - Reaction-based dual signaling of fluoride ions by resorufin sulfonates.
AB  - We developed new reaction-based probes for the dual signaling of fluoride ions.
      Selective fluoride-assisted deprotection of resorufin nosylate to generate
      resorufin fluorochrome was used for signaling. Resorufin nosylate exhibited
      selective colorimetric and fluorogenic signaling of fluoride ions in
      acetonitrile. The response from sulfide ions was effectively masked by using the
      TPEN-Cu(2+) complex as a source of Cu(2+) ions for masking sulfide. Selective
      optical signaling of fluoride was possible in the presence of commonly
      encountered anions with a detection limit of 1.9 * 10(-6) M.

PMID- 23558428
TI  - Having trouble making predictions: Comment on "Predicting disease progression
      after regional therapy for in-transit melanoma".

PMID- 23558429
TI  - Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a
      prospective longitudinal MRI study.
AB  - OBJECTIVE: Longitudinal structural MRI studies have shown that patients with
      schizophrenia have progressive brain tissue loss after onset. Recurrent relapses
      are believed to play a role in this loss, but the relationship between relapse
      and structural MRI measures has not been rigorously assessed. The authors
      analyzed longitudinal data to examine this question. METHODS: The authors studied
      data from 202 patients drawn from the Iowa Longitudinal Study of first-episode
      schizophrenia for whom adequate structural MRI data were available (N=659 scans)
      from scans obtained at regular intervals over an average of 7 years. Because
      clinical follow-up data were obtained at 6-month intervals, the authors were able
      to compute measures of relapse number and duration and relate them to structural
      MRI measures. Because higher treatment intensity has been associated with smaller
      brain tissue volumes, the authors also examined this countereffect in terms of
      dose-years. RESULTS: Relapse duration was related to significant decreases in
      both general (e.g., total cerebral volume) and regional (e.g., frontal) brain
      measures. Number of relapses was unrelated to brain measures. Significant effects
      were also observed for treatment intensity. CONCLUSIONS: Extended periods of
      relapse may have a negative effect on brain integrity in schizophrenia,
      suggesting the importance of implementing proactive measures that may prevent
      relapse and improve treatment adherence. By examining the relative balance of
      effects, that is, relapse duration versus antipsychotic treatment intensity, this
      study sheds light on a troublesome dilemma that clinicians face. Relapse
      prevention is important, but it should be sustained using the lowest possible
      medication dosages that will control symptoms.

PMID- 23558430
TI  - First-trimester serum soluble fms-like tyrosine kinase-1, free vascular
      endothelial growth factor, placental growth factor and uterine artery Doppler in
      preeclampsia.
AB  - OBJECTIVE: To compare the first-trimester serum concentrations of soluble fms
      like tyrosine kinase-1 (sFlt-1), free vascular endothelial growth factor (free
      VEGF), placental growth factor (PlGF), and uterine artery pulsatility index (PI)
      in women who later developed preeclampsia (PE). STUDY DESIGN: Prospectively
      collected maternal serum samples were evaluated for sFlt-1, free VEGF, and PlGF
      levels in 63 cases who later developed PE compared with 252 unaffected controls.
      Serum levels of these angiogenic factors were measured using Quantikine
      immunoassays. Both univariate and multivariate analyses were used to evaluate the
      association between angiogenic factors and PE. The relationship between the
      angiogenic factors and mean maternal uterine artery PI was also evaluated.
      RESULT: Maternal serum sFlt-1 levels were not significantly different between the
      cases and controls. Mean free-VEGF levels were significantly higher in women
      destined to develop PE compared with the controls (P=0.04), and mean PlGF levels
      were significantly lower in women who later developed PE (P=0.01). There was no
      significant correlation between maternal mean uterine artery PI and angiogenic
      factors evaluated. Receiver-operating characteristic curves revealed that none of
      the factors were clinically useful for prediction in the first trimester of PE.
      CONCLUSION: Despite some significant differences in the first-trimester serum
      levels of angiogenic factors, our models suggest that these factors are not
      clinically useful for prediction in women who later developed PE.

PMID- 23558431
TI  - Prenatal and postnatal inflammation in relation to cortisol levels in preterm
      infants at 18 months corrected age.
AB  - OBJECTIVE: To examine whether early inflammation is related to cortisol levels at
      18 months corrected age (CA) in children born very preterm. STUDY DESIGN: Infants
      born <= 32 weeks of gestational age were recruited in the neonatal intensive care
      unit (NICU), and placental histopathology, magnetic resonance imaging (MRI) and
      chart review were obtained. At 18 months CA, developmental assessment and
      collection of three salivary cortisol samples were carried out. Generalized least
      squares was used to analyze data from 85 infants providing 222 cortisol samples.
      RESULT: Infants exposed to chorioamnionitis with funisitis had a significantly
      different pattern of cortisol across the samples compared with infants with
      chorioamnionitis alone or no prenatal inflammation (F(4, 139)=7.3996, P<0.0001).
      Postnatal infections, necrotizing enterocolitis and chronic lung disease were not
      significantly associated with the cortisol pattern at 18 months CA. CONCLUSION:
      In children born very preterm, prenatal inflammatory stress may contribute to
      altered programming of the hypothalamic-pituitary-adrenal (HPA) axis.

PMID- 23558433
TI  - A rare case of pancreatic head splenosis diagnosed by contrast-enhanced
      ultrasound.

PMID- 23558432
TI  - Association of serum adiponectin and insulin-like growth factor I levels with
      parameters of cardiac remodeling in severely obese patients.
AB  - BACKGROUND: Obesity is associated with various changes in cardiac geometry and
      this process involves both hemodynamic and non-hemodynamic factors, among which
      adipocitokines and growth factors may play an important role. The aim of this
      study was to identify the extent and pattern of cardiac remodeling in a group of
      severely obese patients and analyze the relationship between adiponectin, IGFI
      and cardiac parameters reflecting obesity-associated structural changes. SUBJECTS
      AND METHODS: Our study included 344 patients (104 men) with severe obesity [mean
      body mass index (BMI)= 45.7 +/- 8.5 kg/m(2)], extensively evaluated clinically
      and biologically (complete metabolic tests, serum adiponectin, and IGF-I
      measurements). Left ventricular (LV) mass index (LVMI), left atrium (LA) size,
      and LV geometry were determined by means of cardiac ultrasound. RESULTS: The most
      prevalent pattern of LV geometry was eccentric hypertrophy (28.7% of patients).
      In a gender-, age-, BMI-, diabetes- and hypertension-adjusted general linear
      model, patients with concentric or eccentric hypertrophy had significantly lower
      values of adiponectin than those with normal geometry (6.75 +/- 0.41, 6.96 +/-
      0.53, vs 9.04 +/- 0.42 mg/l, p<0.05). In multivariate analysis, independent
      determinants for LVMI were BMI (beta=0.364, p<0.001), systolic blood pressure
      (BP) (beta=0.187, p=0.004), age (beta=0.246, p<0.001), adiponectin (beta=-0.151,
      p=0.012), and IGF-I z-score (beta=0.134, p=0.025) while factors independently
      related to LA size were systolic BP (beta=0.218, p<0.001), BMI (beta=0.194,
      p<0.001), age (beta=0.273, p<0.001), gender (beta=-0.195, p<0.001), and
      adiponectin (beta=-0.180, p=0.005). CONCLUSIONS: In patients with severe obesity,
      IGF-I z score and adiponectin correlate with parameters of cardiac remodeling
      independently of anthropometric, hemodynamic or metabolic factors.

PMID- 23558434
TI  - Hybrid energy harvester based on nanopillar solar cells and PVDF nanogenerator.
AB  - A tandem device which integrates a PVDF nanogenerator and silicon (Si) nanopillar
      solar cell is fabricated. The Si nanopillar solar cell was fabricated using a
      mask-free plasma etching technique and annealing process. The PVDF nanogenerator
      was stacked on top of the Si nanopillar solar cell using a spinning method. The
      optical properties and the device performance of nanowire solar cells have been
      characterized, and the dependence of device performance versus annealing time or
      method has been investigated. Furthermore, the PVDF nanogenerator was operated
      with a 100 dB sound wave and a 0.8 V peak to peak output voltage was generated.
      This tandem device can successfully harvest energy from both sound vibration and
      solar light, demonstrating its strong potential as a future ubiquitous energy
      harvester.

PMID- 23558435
TI  - Hypertrichosis in Becker's nevus: effective low-fluence laser hair removal.
AB  - Becker's nevus is cosmetically bothersome both due to the hyperpigmentation and
      due to the hypertrichosis which can accompany it, particularly in males. Laser
      hair removal can be considered, but the pigmented background of the Becker's
      nevus makes the treatment more challenging. Fifteen patients with Becker's nevus
      underwent eight sessions of hair removal with low-fluence high-repetition-rate
      diode lasers (808-810 nm). All participants experienced significant hair
      reduction at 6 and 12 months. No adverse events were reported. The study supports
      the use of low fluence with high-repetition-rate diode laser hair removal as a
      safe and effective method for the management of hypertrichosis in Becker's nevus.

PMID- 23558436
TI  - Field testing of the Alere DDS2 Mobile Test System for drugs in oral fluid.
AB  - A preliminary field evaluation of a second-generation handheld oral fluid testing
      device, the Alere DDS2 Mobile Test System (DDS2), is described. As part of a
      larger study, drivers were randomly stopped at various locations across
      California (in 2012) and asked to submit voluntarily to a questionnaire regarding
      their drug and alcohol use, a breath alcohol test and collection of oral fluid
      with the Quantisal device. The Quantisal-collected oral fluid samples were sent
      for laboratory-based analyses. At one location, 50 drivers were asked to submit
      an additional oral fluid sample using the DDS2 collection device; these samples
      were analyzed by using the DDS2 mobile test system. Thirty-eight donors (76%)
      provided specimens that were successfully run on the mobile system; in 12 cases
      (24%), the device failed to provide a valid result. Thirty-two of the 38
      collected samples were negative for all drugs; five were positive for
      tetrahydrocannabinol and one was positive for methamphetamine using the mobile
      device. These results corresponded exactly with the laboratory-based results from
      the Quantisal oral fluid collection.

PMID- 23558437
TI  - F0ATP synthase b-chain of Litopenaeus vannamei involved in white spot syndrome
      virus infection.
AB  - White Spot Syndrome Virus (WSSV) is one of the most common and distrous diseases
      for shrimp. In this study, we show that the protein VP292 that is a envelop
      protein of WSVV interacts with F0ATP synthase b-chain from Litopenaeus vannamei
      using far-western blot, ELISA, and indirect immunofluorescence analysis. Tissue
      distribution analysis of F0ATP synthase b-chain showed that it's transcription
      can be detected in muscle, hepatopancreas, intestine, hemocytes, lymphoid, and
      gills. Cellular localization of F0ATP synthase b-chain in shrimp hemocytes showed
      that F0ATP synthase b-chain was primarily located in the cytoplasm of hemocytes.
      The transcription levels of F0ATP synthase b-chain were significantly upregulated
      in intestine, hepatopancreas, hemocytes, and gills of WSSV-infected shrimp at 12
      h after infection. Far-western, ELISA, and indirect immunefluorescence assay
      indicated that F0ATP synthase b-chain interacted with VP292. In the in vivo
      neutralization experiment, F0ATP synthase b-chain attained 18% protection rate of
      the shrimp challenged by WSSV. To the best of our knowledge, this is the first
      report to show that F0ATP synthase b-chain is involved in WSSV infection.

PMID- 23558438
TI  - A novel strategy for the determination of a rhabdovirus genome and its
      application to sequencing of Eggplant mottled dwarf virus.
AB  - A novel strategy employing the rhabdovirus untranslated conserved intergenic
      regions was developed and applied successfully for the determination of the
      complete nucleotide sequence of Eggplant mottled dwarf virus (EMDV). The EMDV
      genome contains seven open reading frames with the same organization as Potato
      yellow dwarf virus (PYDV), the type species of the genus Nucleorhabdovirus. These
      two species encode five core genes [nucleocapsid (N), phosphoprotein (P), matrix
      (M), glycoprotein (G), and the polymerase (L)] like other viruses of the genus
      and an additional one (X), located between N and P, giving rise to a protein with
      currently unknown function. Furthermore, both EMDV and PYDV contain a gene (Y),
      inserted between P and M, which probably encodes the virus movement protein, in
      concordance with the rest of the plant-infecting rhabdoviruses. Phylogenetic
      analysis of the polymerase gene confirmed the classification of EMDV within the
      genus Nucleorhabdovirus and showed a close evolutionary relationship to PYDV. The
      novel sequencing strategy developed is a useful tool for the genome determination
      of yet uncharacterized rhabdoviruses. 

PMID- 23558440
TI  - Transoral endoscopic odontoidectomy to decompress the cervicomedullary junction.
AB  - STUDY DESIGN: Clinical study. OBJECTIVE: To investigate the feasibility of the
      transoral endoscopic odontoidectomy without occipitocervical fusion. SUMMARY OF
      BACKGROUND DATA: Endoscopic transnasal resection of the odontoid process is less
      invasive than the conventional transoral odontoidectomy. However, the endonasal
      approach has a much longer working distance compared with the transoral approach
      to the craniovertebral junction and usually the endonasal approach needs a
      previous occipitocervical posterior fusion. METHODS: From July 2007 to June 2010,
      5 patients (3 males and 2 females, age range, 25-41 yr) with irreducible
      cervicomedullary junction compression were subjected to endoscopic transoral
      odontoidectomy without occipitocervical posterior fixation and bone fusion.
      RESULTS: A purely endoscopic transoral odontoidectomy for decompression of the
      cervicomedullary junction without the occipitocervical fusion was achieved
      successfully in 5 patients. None of the patients underwent tracheotomy and
      postoperative gastrostomy tube placement. The patients were started on liquids on
      the third postoperative day and advanced to a regular diet on the fourth
      postoperative day. There was no postoperative velopharyngeal insufficiency,
      cerebrospinal fluid leakage, regional infection, or meningitis. The patients were
      discharged in 10 to 12 days after the surgery. There were no evidence of
      instability at the craniovertebral junction at 12 to 47 months of follow-up and
      remarkable improvement in neurological function was observed in each patient.
      CONCLUSION: The endoscopic transoral approach may be a more direct route to C1
      and the odontoid than the endoscopic endonasal approach. This approach allows
      complete resection odontoid to decompress the cervicomedullary junction without
      increasing the risk of complications such as wound infection, meningitis, and
      velopharyngeal insufficiency. Usually, the occipitocervical posterior fusion and
      tracheotomy is less necessary in this approach.

PMID- 23558441
TI  - An in vitro model of degenerative lumbar spondylolisthesis.
AB  - STUDY DESIGN: A biomechanical human cadaveric study. OBJECTIVE: To create a
      biomechanical model of low-grade degenerative lumbar spondylolisthesis (DLS),
      defined by anterior listhesis, for future testing of spinal instrumentation.
      SUMMARY OF BACKGROUND DATA: Current spinal implants are used to treat a multitude
      of conditions that range from herniated discs to degenerative diseases. The
      optimal stiffness of these instrumentation systems for each specific spinal
      condition is unknown. Ex vivo models representing degenerative spinal conditions
      are scarce in the literature. A model of DLS for implant testing will enhance our
      understanding of implant-spine behavior for specific populations of patients.
      METHODS: Four incremental surgical destabilizations were performed on 8 lumbar
      functional spinal units. The facet complex and intervertebral disc were targeted
      to represent the tissue changes associated with DLS. After each destabilization,
      the specimen was tested with: (1) applied shear force (-50 to 250 N) with a
      constant axial compression force (300 N) and (2) applied pure moments in flexion
      extension, lateral bending and axial rotation (+/-5 Nm). Relative motion between
      the 2 vertebrae was tracked with a motion capture system. The effect of specimen
      condition on intervertebral motion was assessed for shear and flexibility
      testing. RESULTS: Shear translation increased, specimen stiffness decreased and
      range of motion increased with specimen destabilization (P < 0.0002). A mean
      anterior translation of 3.1 mm (SD 1.1 mm) was achieved only after
      destabilization of both the facet complex and disc. Of the 5 specimen conditions,
      3 were required to achieve grade 1 DLS: (1) intact, (3) a 4-mm facet gap, and (5)
      a combined nucleus and annulus injury. CONCLUSION: Destabilization of both the
      facet complex and disc was required to achieve anterior listhesis of 3.1 mm
      consistent with a grade 1 DLS under an applied shear force of 250 N. Sufficient
      listhesis was measured without radical specimen resection. Important anatomical
      structures for supporting spinal instrumentation were preserved such that this
      model can be used in future to characterize behavior of novel instrumentation
      prior to clinical trials.

PMID- 23558439
TI  - Deletion of the last five C-terminal amino acid residues of connexin43 leads to
      lethal ventricular arrhythmias in mice without affecting coupling via gap
      junction channels.
AB  - The cardiac intercalated disc harbors mechanical and electrical junctions as well
      as ion channel complexes mediating propagation of electrical impulses. Cardiac
      connexin43 (Cx43) co-localizes and interacts with several of the proteins located
      at intercalated discs in the ventricular myocardium. We have generated
      conditional Cx43D378stop mice lacking the last five C-terminal amino acid
      residues, representing a binding motif for zonula occludens protein-1 (ZO-1), and
      investigated the functional consequences of this mutation on cardiac physiology
      and morphology. Newborn and adult homozygous Cx43D378stop mice displayed markedly
      impaired and heterogeneous cardiac electrical activation properties and died from
      severe ventricular arrhythmias. Cx43 and ZO-1 were co-localized at intercalated
      discs in Cx43D378stop hearts, and the Cx43D378stop gap junction channels showed
      normal coupling properties. Patch clamp analyses of isolated adult Cx43D378stop
      cardiomyocytes revealed a significant decrease in sodium and potassium current
      densities. Furthermore, we also observed a significant loss of Nav1.5 protein
      from intercalated discs in Cx43D378stop hearts. The phenotypic lethality of the
      Cx43D378stop mutation was very similar to the one previously reported for adult
      Cx43 deficient (Cx43KO) mice. Yet, in contrast to Cx43KO mice, the Cx43 gap
      junction channel was still functional in the Cx43D378stop mutant. We conclude
      that the lethality of Cx43D378stop mice is independent of the loss of gap
      junctional intercellular communication, but most likely results from impaired
      cardiac sodium and potassium currents. The Cx43D378stop mice reveal for the first
      time that Cx43 dependent arrhythmias can develop by mechanisms other than
      impairment of gap junction channel function.

PMID- 23558442
TI  - Exercises for adolescent idiopathic scoliosis: a Cochrane systematic review.
AB  - STUDY DESIGN: Systematic review of interventions. OBJECTIVE: To evaluate the
      efficacy of scoliosis-specific exercise (SSE) in adolescent patients with
      adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: AIS is a 3
      dimensional deformity of the spine. Although AIS can progress during growth and
      cause a surface deformity, it is usually not symptomatic. However, in adulthood,
      if the final spinal curvature surpasses a certain critical threshold, the risk of
      health problems and curve progression is increased. The use of SSEs to reduce
      progression of AIS and postpone or avoid other more invasive treatments is
      controversial. METHODS:  SEARCH METHODS: The following databases (up to March 30,
      2011) were searched with no language limitations: CENTRAL (The Cochrane Library
      2011, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), CINHAL
      (from January 1982), SPORTDiscus (from January 1975), PsycINFO (from January
      1887), and PEDro (from January 1929). We screened reference lists of articles and
      conducted an extensive hand search of gray literature. SELECTION CRITERIA:
      randomized controlled trials and prospective cohort studies with a control group
      comparing exercises with no treatment, other treatment, surgery, and different
      types of exercises. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected studies, assessed risk of bias and extracted data.
      RESULTS: Two studies (154 participants) were included. There is low-quality
      evidence from 1 randomized controlled study that exercises as an adjunctive to
      other conservative treatments to increase the efficacy of these treatments
      (thoracic curve reduced: mean difference 9.00, [95% confidence interval, 5.47
      12.53]; lumbar curve reduced: mean difference 8.00, [95% confidence interval,
      5.08-10.92]). There is very low-quality evidence from a prospective controlled
      cohort study that SSEs structured within an exercise program can reduce brace
      prescription (risk ratio, 0.24; [95% confidence interval, 0.06-1.04]) as compared
      with "usual physiotherapy" [many different kinds of general exercises according
      to the preferences of the single therapists within different facilities]).
      CONCLUSION: There is a lack of high-quality evidence to recommend the use of SSE
      for AIS. One very low-quality study suggested that these exercises may be more
      effective than electrostimulation, traction, and postural training to avoid
      scoliosis progression, but better quality research needs to be conducted before
      the use of SSE can be recommended in clinical practice. LEVEL OF EVIDENCE: 2.

PMID- 23558443
TI  - Associations between urinary soy isoflavonoids and two inflammatory markers in
      adults in the United States in 2005-2008.
AB  - PURPOSE: The aim of this study was to determine the association between urinary
      isoflavonoid (genistein, daidzein, and the daidzein metabolites O
      desmethylangolensin (O-DMA) and equol) excretion and markers of inflammation in
      adults in the United States in National Health and Nutrition Examination Survey
      (NHANES) 2005-2008. METHODS: The NHANES is a cross-sectional study conducted by
      the National Center for Health Statistics to study the health and nutritional
      status of people living in the United States. The analysis included 1,683
      participants from study years 2005-2008 for whom urinary isoflavonoids were
      measured and who met inclusion criteria. Urinary isoflavonoids were measured by
      HPLC-APPI-MS/MS. Serum C-reactive protein (CRP) was measured by latex-based
      nephelometry. White blood cell (WBC) count was measured by Coulter counting.
      Multivariable linear regression was used to calculate the geometric mean values
      of the markers, and multivariable logistic regression was used to estimate the
      odds of high CRP (>=3 mg/L) and of high WBC count (>=7,900/MUL) by quartile of
      urinary isoflavonoid (nmol/mg creatinine). RESULTS: The highest quartile of
      genistein (OR = 0.62; 95 % CI 0.39-0.99) was associated with significantly
      decreased odds of high CRP compared with the lowest quartile. The sum of daidzein
      and its metabolites was significantly inversely associated with serum CRP
      concentration (p-trend = 0.017). Equol was inversely associated with WBC count (p
      trend < 0.0001). O-DMA was the only isoflavonoid whose excretion was
      significantly associated with a decrease in both CRP (p-trend = 0.024) and WBC
      count (p-trend < 0.0001). CONCLUSIONS: Though no clear pattern emerged, higher
      excretion of certain soy isoflavonoids was associated with decreased CRP
      concentration and WBC counts, suggesting a possible inverse association between
      soy intake and inflammation.

PMID- 23558445
TI  - Exposure to pesticides and the risk of childhood brain tumors.
AB  - PURPOSE: Previous research has suggested positive associations between parental
      or childhood exposure to pesticides and risk of childhood brain tumors (CBT).
      This Australian case-control study of CBT investigated whether exposures to
      pesticides before pregnancy, during pregnancy and during childhood, were
      associated with an increased risk. METHODS: Cases were recruited from 10
      pediatric oncology centers, and controls by random-digit dialing, frequency
      matched on age, sex, and State of residence. Exposure data were collected by
      written questionnaires and telephone interviews. Data were analyzed by
      unconditional logistic regression. RESULTS: The odds ratios (ORs) for
      professional pest control treatments in the home in the year before the index
      pregnancy, during the pregnancy, and after the child's birth were 1.54 (95%
      confidence interval (CI): 1.07, 2.22), 1.52 (95% CI: 0.99, 2.34) and 1.04 (95%
      CI: 0.75, 1.43), respectively. ORs for treatments exclusively before pregnancy
      and during pregnancy were 1.90 (95% CI: 1.08, 3.36) and 1.02 (95% CI: 0.35,
      3.00), respectively. The OR for the father being home during the treatment was
      1.79 (95% CI: 0.85, 3.80). The OR for paternal occupational exposure in the year
      before the child's conception was 1.36 (95% CI: 0.66, 2.80). ORs for prenatal
      home pesticide exposure were elevated for low- and high-grade gliomas; effect
      estimates for other CBT subtypes varied and lacked precision. CONCLUSIONS: These
      results suggest that preconception pesticide exposure, and possibly exposure
      during pregnancy, is associated with an increased CBT risk. It may be advisable
      for both parents to avoid pesticide exposure during this time.

PMID- 23558444
TI  - The effect of multiple primary rules on population-based cancer survival.
AB  - PURPOSE: Different rules for registering multiple primary (MP) cancers are used
      by cancer registries throughout the world, making international data comparisons
      difficult. This study evaluates the effect of Surveillance, Epidemiology, and End
      Results (SEER) and International Association of Cancer Registries (IACR) MP rules
      on population-based cancer survival estimates. METHODS: Data from five US states
      and six metropolitan area cancer registries participating in the SEER Program
      were used to estimate age-standardized relative survival (RS%) for first cancers
      only and all first cancers matching the selection criteria according to SEER and
      IACR MP rules for all cancer sites combined and for the top 25 cancer site groups
      among men and women. RESULTS: During 1995-2008, the percentage of MP cancers (all
      sites, both sexes) increased 25.4 % by using SEER rules (from 14.6 to 18.4 %) and
      20.1 % by using IACR rules (from 13.2 to 15.8 %). More MP cancers were registered
      among females than among males, and SEER rules registered more MP cancers than
      IACR rules (15.8 vs. 14.4 % among males; 17.2 vs. 14.5 % among females). The top
      3 cancer sites with the largest differences were melanoma (5.8 %), urinary
      bladder (3.5 %), and kidney and renal pelvis (2.9 %) among males, and breast (5.9
      %), melanoma (3.9 %), and urinary bladder (3.4 %) among females. Five-year
      survival estimates (all sites combined) restricted to first primary cancers-only
      were higher than estimates by using first site-specific primaries (SEER or IACR
      rules), and for 11 of 21 sites among males and 11 of 23 sites among females. SEER
      estimates are comparable to IACR estimates for all site-specific cancers and
      marginally higher for all sites combined among females (RS 62.28 vs. 61.96 %).
      CONCLUSION: Survival after diagnosis has improved for many leading cancers.
      However, cancer patients remain at risk of subsequent cancers. Survival estimates
      based on first cancers-only exclude a large and increasing number of MP cancers.
      To produce clinically and epidemiologically relevant and less biased cancer
      survival estimates, data on all cancers should be included in the analysis. The
      multiple primary rules (SEER or IACR) used to identify primary cancers do not
      affect survival estimates if all first cancers matching the selection criteria
      are used to produce site-specific survival estimates.

PMID- 23558447
TI  - North Dakota passes restrictive abortion laws that may reach the Supreme Court.

PMID- 23558446
TI  - Inhibition of platelet-derived growth factor receptor alpha by MEDI-575 reduces
      tumor growth and stromal fibroblast content in a model of non-small cell lung
      cancer.
AB  - Platelet-derived growth factor receptor alpha (PDGFRalpha) is a receptor tyrosine
      kinase that promotes cell survival and is expressed in both the tumor and the
      stromal components of human cancers. We have developed a fully human monoclonal
      antibody, MEDI-575, that selectively binds to human PDGFRalpha with high
      affinity, with no observable affinity for murine PDGFRalpha. To more fully
      characterize the role of PDGFRalpha in the regulation of tumor stroma, we
      evaluated the in vivo antitumor effects of MEDI-575 in tumor-bearing severe
      combined immunodeficient (SCID) mice and in genetically altered SCID mice
      expressing human PDGFRalpha in place of murine PDGFRalpha. We used the Calu-6 non
      small cell lung cancer model because it lacks an in vitro proliferative response
      to PDGFRalpha activation. Antitumor activity was observed when the study was
      performed in mice expressing the human receptor, but no activity was observed in
      the mice expressing the murine receptor. Immunohistologic analysis of the tumors
      from mice expressing human PDGFRalpha showed a highly significant reduction in
      stromal fibroblast content and only minor changes in tumor proliferative index in
      tumors exposed to MEDI-575 compared with the results seen in vehicle-treated
      tumors or in tumors from mice expressing murine PDGFRalpha. Additional in vitro
      studies indicated that exposure of primary cancer-associated fibroblasts to MEDI
      575 can directly affect proliferation and key signaling pathways in these cells.
      These results highlight the potential for observing antitumor activity with MEDI
      575 through modulation of the stromal component of tumors and confirm that the
      PDGFRalpha pathway can play a role in maintaining a tumor microenvironment
      conducive to tumor growth.

PMID- 23558449
TI  - Effects of intramolecular hydrogen bonding on the excited state dynamics of
      phenol chromophores.
AB  - The theoretical prediction and experimental confirmation of the 1pisigma* excited
      state of phenol which is repulsive along the O-H bond has a large impact on the
      interpretation of phenol and tyrosine photochemistry. In this work, we
      demonstrate that this excited state changes significantly if the OH functional
      group is involved in the formation of an intramolecular hydrogen bond in the
      ground state. We investigate the excited state dynamics of 2-, 3-, and 4
      hydroxyacetophenone (HAP) separately in a molecular beam at 193 nm using
      multimass ion imaging techniques. H atom elimination from the repulsive excited
      state and Norrish type I reactions are the major dissociation channels of 3-HAP
      and 4-HAP which do not have intramolecular hydrogen bonding. However, the H atom
      elimination channel is completely quenched for 2-HAP which shows intramolecular
      hydrogen bonding. In addition, the ground state and the excited state potential
      energy surfaces (PESs) of HAP, 2-hydroxybenzoyl fluoride, 2-hydroxybenzoyl
      chloride, and 2-hydroxybenzamide are investigated using ab initio calculations.
      The results also show that the excited state potential along the O-H bond
      distance of the hydroxyl group changes significantly for molecules with
      intramolecular hydrogen bonding. The changes include: (a) the repulsive potential
      energy surface becomes an attractive potential near the ground state equilibrium
      geometry, (b) the conical intersection between the first and the second excited
      states along the O-H bond moves to a much higher energy level, and (c) the
      conical intersection between the repulsive excited state and the ground state
      along the O-H bond distance disappears. The results suggest that the
      interpretation of the photochemistry for molecules with a phenol chromophore must
      take these effects into consideration.

PMID- 23558448
TI  - Association of allergic rhinitis or asthma with pollen and chemical pollutants in
      Szeged, Hungary, 1999-2007.
AB  - The effect of biological (pollen) and chemical air pollutants on respiratory
      hospital admissions for the Szeged region in Southern Hungary is analysed. A 9
      year (1999-2007) database includes--besides daily number of respiratory hospital
      admissions--daily mean concentrations of CO, PM10, NO, NO2, O3 and SO2. Two
      pollen variables (Ambrosia and total pollen excluding Ambrosia) are also
      included. The analysis was performed for patients with chronic respiratory
      complaints (allergic rhinitis or asthma bronchiale) for two age categories
      (adults and the elderly) of males and females. Factor analysis was performed to
      clarify the relative importance of the pollutant variables affecting respiratory
      complaints. Using selected low and high quantiles corresponding to probability
      distributions of respiratory hospital admissions, averages of two data sets of
      each air pollutant variable were evaluated. Elements of these data sets were
      chosen according to whether actual daily patient numbers were below or above
      their quantile value. A nonparametric regression technique was applied to
      discriminate between extreme and non-extreme numbers of respiratory admissions
      using pollen and chemical pollutants as explanatory variables. The strongest
      correlations between extreme patient numbers and pollutants can be observed
      during the pollen season of Ambrosia, while the pollen-free period exhibits the
      weakest relationships. The elderly group with asthma bronchiale is characterised
      by lower correlations between extreme patient numbers and pollutants compared to
      adults and allergic rhinitis, respectively. The ratio of the number of correct
      decisions on the exceedance of a quantile resulted in similar conclusions as
      those obtained by using multiple correlations.

PMID- 23558450
TI  - Assessment of lung toxicity caused by bleomycin and amiodarone by Tc-99m HMPAO
      lung scintigraphy in rats.
AB  - AIM: The purpose of the study was to determine the lung toxicity caused by
      amiodarone (AD) and bleomycin (BLM) in rats, by means of Tc-99m HMPAO lung
      scintigraphy. METHODS: Thirty albino rats were randomly divided into five groups.
      After AD or BLM was dissolved with isotonic saline (SF), a 0.5 ml solution was
      applied to the right bronchus via a catheter. Group 1 (n = 5 rats) received a
      single dose of AD, group 2 (n = 5) received two doses of AD, group 3 (n = 9)
      received BLM, group 4 (n = 3) received hydrochloric acid (HCl), and group 5 (n =
      8) received SF. Rats in groups 1, 2, 3 and 5 were given 37 MBq Tc-99m HMPAO from
      the tail vein on days 7, 14, 21 and 28, and at 4 and 24 h in group 4. Static
      images of 10 min duration were obtained at 30 and 60 min by a double-headed gamma
      camera (Infinia, GE, Tirat Hacermel, Israel) on 256 * 256 matrix. Regular regions
      of interests were drawn over the right lung (RL), left lung (LL) and the liver
      (Li), and lung/liver (L/Li) ratios were calculated. After the scintigraphic
      imaging procedures were completed, rats were killed. Lung tissues were evaluated
      on a scale of (+) to (+++++) for edema, alveolar structural integrity and
      infiltration by inflammatory cells. RESULTS: Groups 2 and 3 showed statistically
      significant differences in RL/Li and LL/Li ratios, whereby RL/Li was higher than
      LL/Li (p < 0.05). There were no significant differences in RL/Li and LL/Li ratios
      in group 5 (p > 0.05). In histopathological examination, minimal damage or
      artifacts were observed in group 5. In group 4, almost all pathological findings
      were present in the right lung. Statistically significant (p < 0.01) histological
      differences were found when groups 1 and 5 were compared. More significant (p <
      0.001) pathological effects were noted when groups 2 and 3 were compared to both
      groups 5 and 1. Injury was more prominent in the lung tissues of the control rats
      that were given HCl. Increased RL/Li ratios and histopathological findings were
      consistent. CONCLUSION: Tc-99m HMPAO lung scan are found to be useful in the
      identification of patients with lung toxicity. The simplicity of the procedure
      and lower radiation exposure are the advantages of Tc-99m HMPAO lung scan.

PMID- 23558454
TI  - Central facial paresis and its impact on mimicry, psyche and quality of life in
      patients after stroke.
AB  - AIM: Using functional scales and face video analysis, changes in central facial
      paresis are monitored in patients with stroke after orofacial therapy and
      correlations between changes in mimicry, mental function and overall quality of
      life of patients after stroke are made. MATERIALS AND METHODS: A prospective
      randomized study of patients after stroke with facial paresis. The functional
      status of the experimental group of 50 cases with orofacial regulation therapy
      and 49 control cases without mimicry therapy is observed after four weeks of
      rehabilitation. RESULTS: Changes in mimicry functions evaluated by the House
      Brackmann Grading System (HBGS) clinical range and using 2D video analysis of the
      distance between the paretic corner of the mouth and earlobe at rest and during
      smiling were statistically better in the experimental group than in controls.
      Changes in mental function - depression using Beck Depression Inventory and
      changes in the quality of life using Bartle index and modified Rankin score
      (scale) were significantly greater in the experimental group. There was a very
      close relationship between the changes in mimicry, mental state and overall
      quality of life according to the Spearman correlative coefficient. CONCLUSION:
      Orofacial rehabilitation therapy for patients with paresis after stroke has a
      significant influence on the adjustment of mimicry, mental functions and overall
      quality of life after 4 weeks of treatment.

PMID- 23558452
TI  - Cognitive experiences reported by patients with borderline personality disorder
      and axis II comparison subjects: a 16-year prospective follow-up study.
AB  - OBJECTIVE: The authors assessed three main types of disturbed cognition:
      nonpsychotic thought (odd thinking, unusual perceptual experiences, and
      nondelusional paranoia), quasi-psychotic thought, and true psychotic thought in
      patients with borderline personality disorder followed prospectively for 16
      years. They also compared the rates of these disturbed cognitions with those
      reported by axis II comparison subjects. METHOD: The cognitive experiences of 362
      inpatients (290 borderline patients and 72 axis II comparison subjects) were
      assessed at study entry using the cognitive section of the Revised Diagnostic
      Interview for Borderlines. Participants' cognitive experiences were reassessed
      every 2 years using the same interview. RESULTS: Each of the five main types of
      thought studied was reported by a significantly higher percentage of patients in
      the borderline group than in the axis II comparison group over time. Each of
      these types of thought, except true psychotic thought, declined significantly
      over time for participants in both groups. Eleven of the 17 more specific forms
      of thought studied were also reported by a significantly higher percentage of
      patients in the borderline group over the follow-up period: magical thinking,
      overvalued ideas, recurrent illusions, depersonalization, derealization, undue
      suspiciousness, ideas of reference, other paranoid ideation, quasi-psychotic
      delusions, quasi-psychotic hallucinations, and true psychotic hallucinations.
      Fourteen specific forms of thought were found to decline significantly over time
      for participants in both groups: all forms of thought mentioned above except true
      psychotic hallucinations plus marked superstitiousness, sixth sense, telepathy,
      and clairvoyance. CONCLUSIONS: Disturbed cognitions are common in patients with
      borderline personality disorder and are distinguishing for the disorder. They
      also decline substantially over time but remain a problem, particularly those of
      a nonpsychotic nature.

PMID- 23558455
TI  - Iron-catalysed oxidative amidation of alcohols with amines.
AB  - A new iron-catalysed oxidative amidation of differently substituted benzylic
      alcohols with mono- and di-substituted amines was developed.

PMID- 23558456
TI  - Thermoelectric properties of a quantum dot array connected to metallic
      electrodes.
AB  - The thermoelectric properties of a quantum dot array (QDA) embedded in a nanowire
      connected to metallic electrodes are investigated theoretically via the extended
      Hubbard model in the Coulomb blockade regime. Coupled quantum dots (QDs) with dot
      number N = 2-5 are considered. It is found that the thermoelectric properties
      converge to almost the same results when N approaches 5, indicating that our
      results are applicable for a QDA with a large number of QDs. Our studies indicate
      that in order to achieve the optimal figure of merit (ZT), it is preferable to
      have the QD energy levels above the Fermi energy (EF) of the electrodes of the
      QDA junction. The effects of QD energy level and interdot coupling variations
      (due to the QD size and position fluctuation) on the thermoelectric properties
      are also examined. We find that the QD size fluctuation significantly suppresses
      the maximum ZT in the weak interdot hopping strength (tl,j). We also find that
      the Seebeck coefficient is insensitive to tl,j and the tunneling rates when the
      QD energy levels are far above EF. For a given tl,j and large on-site Coulomb
      interactions, increasing the QD number N in the QDA would suppress the maximum ZT
      value. It is possible to achieve an optimal ZT larger than 3 by tailoring the
      physical parameters of the QDA junction system.

PMID- 23558458
TI  - Petersen's hernia after laparoscopic distal gastrectomy with Roux-en-Y
      reconstruction for gastric cancer.
AB  - BACKGROUND: To decrease the incidence of internal hernia after laparoscopic Roux
      en-Y gastric bypass, recent recommendations indicated closure of mesenteric
      defects and Petersen's defect. Laparoscopic distal gastrectomy for gastric cancer
      is used increasingly, so the incidence of Petersen's hernia can also increase,
      but the trend has not been studied. METHODS: This study retrospectively reviewed
      358 consecutive patients who underwent laparoscopic distal gastrectomy for
      gastric cancer at one institution, with antecolic Roux-en-Y (RY) reconstruction.
      RESULTS: Petersen's hernia occurred in 6 (2.2 %) of 268 patients whose Petersen's
      defect was not closed by a mean of 351 days after surgery. All the patients
      underwent reoperation with reduction and repair of the hernia except the first
      case. In 90 subsequent cases, with closure of the Petersen's defect, internal
      hernias did not occur (0/90 cases; p = 0.06). Focusing on the totally
      laparoscopic procedure, Petersen's hernia occurred in 2 (5.1 %) of 39 patients,
      whereas in 81 subsequent cases, with closure of Petersen's defect, internal
      hernias did not occur (0/81 cases; p = 0.03). CONCLUSIONS: Based on the recent
      recommendations for bariatric surgery, closure of this potential hernia defect is
      necessary after laparoscopic distal gastrectomy with R-Y reconstruction for
      gastric cancer.

PMID- 23558457
TI  - Expression of CD133 in the cytoplasm is associated with cancer progression and
      poor prognosis in gastric cancer.
AB  - BACKGROUND: CD133 is one of the most important stem cell markers in solid
      cancers. Some recent reports have described a possible relationship between CD133
      and hypoxia-inducing factor-1-alpha (HIF-1alpha). The aim of this study was to
      clarify the clinical role of CD133 expression in gastric cancer and to
      investigate the correlation between CD133 expression and HIF-1alpha expression.
      METHODS: We studied 189 gastric cancer patients who underwent gastrectomy at
      Kurume University Hospital. CD133 and HIF-1alpha expression was examined using
      immunohistochemical staining. Fifty-six cases were CD133 positive, and they were
      divided into two expression types: luminal expression of the gland and
      cytoplasmic expression. We investigated the relationship among CD133 expression
      types, clinicopathological variables, prognosis, and HIF-1alpha expression.
      RESULTS: When comparing clinicopathological variables, expression of CD133 in the
      cytoplasm was related to metastasis and tumor progression. However, this
      relationship was not observed with luminal expression of the gland type. The
      survival rate in patients with cytoplasmic CD133 expression was significantly
      worse than that in the CD133-negative group. This relationship was observed in
      the survival rate of the adjuvant chemotherapy group and the curative resection
      group. Multivariate analysis revealed that the expression of CD133 in the
      cytoplasm was an independent prognostic factor in gastric cancer. Regarding the
      correlation between CD133 expression and HIF-1alpha expression, the HIF-1alpha
      positive rate was lower in patients with CD133 luminal expression of the gland
      type and higher in patients with cytoplasmic expression of CD133. CONCLUSION:
      Gastric cancer cells with CD133 expression in the cytoplasm were cells with high
      potential for malignancy, and this phenotype was associated with cancer
      progression, chemotherapy resistance, recurrence, and poor prognosis. Cytoplasmic
      expression of CD133 may be a useful prognostic marker in gastric cancer.
      Significant correlation was observed between HIF-1alpha expression and the
      immunohistochemical staining pattern of CD133.

PMID- 23558459
TI  - Long-term outcomes of patients who underwent limited proximal gastrectomy.
AB  - BACKGROUND: Because the incidence of early gastric cancers has been increasing in
      Asian countries, postoperative quality of life has received considerable
      attention in addition to oncological outcomes. METHODS: Eighty-four patients with
      clinically early gastric cancers were enrolled in this retrospective study. Among
      them, 35 patients underwent total gastrectomy (TG) and 49 patients underwent
      limited proximal gastrectomy (PG). Blood chemistry, changes in body weight, and
      oncological outcomes were compared between the two groups. RESULTS: Postoperative
      hemoglobin levels and body weights were significantly lower in the TG group than
      in the PG group, and there were no significant differences in the levels of other
      nutritional indicators such as serum total protein and total cholesterol.
      However, the overall survival rates of patients in the PG group were similar to
      those of patients in the TG group (5-year survival rates, 95 versus 97 %,
      respectively; p = 0.86). CONCLUSIONS: Limited proximal gastrectomy with regional
      lymph node dissection has possible positive effects on maintaining body weight
      and preventing postgastrectomy anemia with similar oncological outcomes to total
      gastrectomy in patients with early gastric cancers.

PMID- 23558460
TI  - Andrimid production at low temperature by a psychrotolerant Serratia
      proteamaculans strain.
AB  - Andrimid, a known non-ribosomal pseudo-peptide antibiotic, was isolated from a
      psychrotolerant Serratia proteamaculans strain. The antibiotic peptide was
      produced at low temperature (8  degrees C) in a 7.5 l BIOFLO 101 bioreactor under
      batch culture mode. Andrimid activity from S. proteamaculans culture was only
      detected at 25  degrees C and below and potent antibacterial activity was
      revealed against both, pathogenic and non-pathogenic bacteria. Minimal inhibitory
      concentration values determined by microdilution experiments varied in the range
      between 0.01 and 0.78 MUg/ml. Antimicrobial purification and structure
      elucidation were carried out by LC-MS/MS and 1H/13C NMR approaches. The effects
      on the ultrastructure of sensitive Escherichia coli 35,218 cells were observed by
      transmission electron microscopy at different inhibition stages. This work
      demonstrated the significance of bioprospection from cold environments through
      the screening of microorganisms with ability to produce cold-active biomolecules
      of biotechnological interest. S. proteamaculans 136 was revealed as a novel
      microbial source for andrimid production at low temperatures, showing
      biotechnological potential to be applied in cryopreservation, food or cosmetic
      industries against pathogenic bacteria.

PMID- 23558462
TI  - Fetal MRI.

PMID- 23558461
TI  - Size-appropriate radiation doses in pediatric body CT: a study of regional
      community adoption in the United States.
AB  - BACKGROUND: During the last decade, there has been a movement in the United
      States toward utilizing size-appropriate radiation doses for pediatric body CT,
      with smaller doses given to smaller patients. OBJECTIVE: This study assesses
      community adoption of size-appropriate pediatric CT techniques. Size-specific
      dose estimates (SSDE) in pediatric body scans are compared between community
      facilities and a university children's hospital that tailors CT protocols to
      patient size as advocated by Image Gently. MATERIALS AND METHODS: We compared 164
      pediatric body scans done at community facilities (group X) with 466 children's
      hospital scans. Children's hospital scans were divided into two groups: A, 250
      performed with established pediatric weight-based protocols and filtered back
      projection; B, 216 performed with addition of iterative reconstruction technique
      and a 60% reduction in volume CT dose index (CTDIvol). SSDE was calculated and
      differences among groups were compared by regression analysis. RESULTS: Mean SSDE
      was 1.6 and 3.9 times higher in group X than in groups A and B and 2.5 times
      higher for group A than group B. A model adjusting for confounders confirmed
      significant differences between group pairs. CONCLUSIONS: Regional community
      hospitals and imaging centers have not universally adopted child-sized pediatric
      CT practices. More education and accountability may be necessary to achieve
      widespread implementation. Since even lower radiation doses are possible with
      iterative reconstruction technique than with filtered back projection alone,
      further exploration of the former is encouraged.

PMID- 23558463
TI  - Fetal MRI: the sonographer's view.
AB  - Fetal magnetic resonance imaging (MRI) is used with increasing frequency as a
      complementary imaging modality to ultrasound (US) in prenatal diagnosis. Fetal
      MRI displays the fetal, uterine, and extrauterine anatomy in ways that allow
      confirmation of normal anatomy and the diagnosis of pathological entities that
      were formerly very difficult to detect prenatally. Comparison of US views with
      standard orthogonal plane MR images reinforces the understanding of fetal anatomy
      as visualized with US. Technological advances in US equipment have allowed the
      recent description of subtle fetal anatomical structures. Similarly, knowledge of
      the MRI appearances of pathological conditions has opened opportunities for the
      sonographic diagnosis of entities such as brainstem malformations and alterations
      in the normal transient laminar pattern that occur during development of the
      fetal cerebrum. Fetal MRI can confirm suspicious US findings and thus add
      confidence in a particular prenatal diagnosis before performing invasive and
      interventional procedures. Specific MRI sequences can be used to add information
      about the chemical composition of fetal structures, such as fat, blood, and
      meconium. Dynamic MRI sequences have increased understanding of gestational age
      dependent behavior, and assist the sonographer in assessment of fetal structural
      anomalies that cause abnormal movement and behavior. The technological ability of
      US to demonstrate very small structures complements the lower resolution of fetal
      MR images, whereas the ability of MR to visualize the whole fetus improves the
      limited views necessitated by US. Therefore, both US and fetal MRI have
      complementary strengths and weaknesses that can be used to full advantage in
      prenatal diagnosis.

PMID- 23558464
TI  - Skeletal development on fetal magnetic resonance imaging.
AB  - Prenatal magnetic resonance imaging (MRI) is being increasingly used, in addition
      to standard ultrasound, for the diagnosis of congenital diseases beyond the
      central nervous system. Previous studies have demonstrated that MRI may be useful
      for the in utero visualization of spinal dysraphism and for differentiating
      between isolated and complex skeletal disorders with associated abnormalities.
      More recently, attention has focused on the visualization of the human fetal
      skeleton for the delineation of normal and pathological development of skeletal
      structures. On 1.5 T, in particular, echoplanar imaging enables the delineation
      of various epimetaphyseal structures and morphometric measurements of the fetal
      long bones from 18 gestational weeks until term. This information gathered from
      prenatal MRI might be helpful in the diagnosis of focal bone abnormalities and
      generalized skeletal disorders, such as bone dysplasias. Further clinical
      research, along with the refinement of the newest techniques, will enable
      expansion of the preliminary findings and help in determining the impact of fetal
      magnetic resonance bone imaging in the routine clinical setting. This review
      summarizes the current data in the literature and the authors' clinical
      experience with the magnetic resonance visualization of the developing fetal
      skeleton and also comments on the potential future applications of this
      technique.

PMID- 23558465
TI  - Atlas learning in fetal brain development.
AB  - Magnetic resonance imaging has become an important noninvasive technique to gain
      insight into fetal brain development. Its capabilities go beyond ultrasound when
      diagnosing high-risk pregnancies. To summarize observations across a population
      in magnetic resonance imaging studies, reference systems such as atlases that
      establish correspondences across a cohort are key. In this article, we review the
      evolution of atlas-building methods in light of their relevance, limitations, and
      benefits for the modeling of human brain development. Starting with single
      anatomical templates to which brain scans where mapped to such as Talairach and
      Montreal Neurological Institute space, we explore the uses of atlases as a means
      to establish correspondences across a cohort and as a model that captures the
      population characteristics of the cases the atlas is built from. We discuss
      methods that capture features of increasingly heterogeneous populations and
      approaches that are able to generalize with only minimal annotation. The main
      focus of this review are methods that explicitly model the variability in the
      population with regard to time, such as in the modeling of disease progression
      and brain development. We highlight the applicability and limitations of state-of
      the art approaches, how insights from the study of disease progression are
      helpful in developmental studies, and point to the directions of future research
      that is still necessary.

PMID- 23558466
TI  - Functional imaging in the fetus.
AB  - This review focuses on the application of magnetic resonance imaging methods in
      utero studying functional brain development of spontaneous brain activity
      generated under resting conditions and of task-evoked activity using stimulation.
      These imaging approaches have been useful to explore the brain's functional
      organization during development, as already shown in different substantial
      resting-state studies in preterms. We also discuss emerging future directions
      regarding analyzing methods and combination of functional and structural
      connectivity approaches.

PMID- 23558467
TI  - Fetal magnetic resonance imaging at 3.0 T.
AB  - Magnetic resonance imaging (MRI) has been used to image the in utero fetus for
      the past 3 decades. Although not as commonplace as other patient-oriented MRI, it
      is a growing field and demonstrating a role in the clinical care of the fetus.
      Indeed, the body of literature involving fetal MRI exceeds 3000 published
      articles. Indeed, there is interest in accessing even the healthy fetus with MRI
      to further understand the development of humans during the fetal stage. On the
      horizon is fetal imaging using 3.0-T clinical systems. Although a clear path is
      not necessarily determined, experiments, theoretical calculations, advances in
      pulse sequence design, new hardware, and experience from imaging at 1.5 T help
      define the path.

PMID- 23558468
TI  - Predictors and incidence of stent edge dissections in patients with type 2
      diabetes as determined by optical coherence tomography.
AB  - Patients with type 2 diabetes are at increased risk for post-PCI complications
      including stent thrombosis and restenosis. Stent edge dissections (SEDs) have
      been associated with these complications. This study assessed incidence and
      predictors of SEDs in patients with type 2 diabetes using optical coherence
      tomography (OCT). Intravascular lesion parameters and plaque morphology were
      investigated pre- and post-PCI using OCT in 73 type 2 diabetic patients with 90
      lesions and 166 visible stent edges. We detected 42 (25.3 %) SEDs in 166 stent
      edges and 37 (41.1 %) SEDs in 90 lesions. More SEDs occurred if the border of the
      stent had been placed within diseased vessel segments with predominantly fibrous
      (42.9 %) and fibrocalcific (40.5 %) plaques compared to healthy vessel wall
      morphology (p < 0.001). Furthermore, the lumen eccentricity of the stent at its
      edges (SAE) (16.00 +/- 6.07 vs. 13.11 +/- 5.22 %, p < 0.003) and the stent-edge
      to-lumen-area-ratio (1.26 +/- 0.27 vs. 0.99 +/- 0.20, p < 0.001) were both
      significantly larger in the presence of SEDs. All of the above parameters were
      significant predictors for SEDs on uni- and multivariate logistic regression
      analysis (all p < 0.01), suggesting that the lumen eccentricity of the SAE, the
      stent-edge-to-lumen-area-ratio and diseased vessel wall morphology of the
      reference segment adjacent to the stent edge are independent risk factors for the
      presence of SEDs. These results suggest that diseased vessel wall morphology at
      the stent edges may promote the occurrence of SEDs and that avoidance of
      longitudinal and transverse mismatch between stent and vessel could be important
      to reduce SEDs in cardiovascular high-risk patients with type 2 diabetes.

PMID- 23558469
TI  - Awareness and management of hyponatraemia: the Italian Hyponatraemia Survey.
AB  - BACKGROUND: Hyponatraemia is the most frequent electrolyte disorder in
      hospitalized patients and has been associated with increased morbidity, mortality
      and length of hospital stay. There is evidence that also mild chronic
      hyponatraemia may have clinical consequences, such as gait disturbances,
      attention deficits, falls, increased risk of fractures and reduced bone mineral
      density. Nevertheless, this condition appears to be rather often not taken into
      consideration, or inappropriately managed and treated, thus negatively affecting
      patients' outcome. AIM: The aim of this study was to investigate the awareness
      and management of hyponatraemia secondary to SIAD, a common cause of
      hyponatraemia, among Italian physicians (endocrinologists, nephrologists,
      internists) commonly involved as consultants. METHODS: A questionnaire, covering
      definition, diagnosis, management, treatment and prognosis of hyponatraemia
      secondary to SIAD, was developed with the support of the Italian Society of
      Endocrinology. RESULTS: Among the respondents (n=275), the majority was aware of
      the negative implications of hyponatraemia or of an inappropriate treatment.
      Nevertheless, the answers indicated that SIAD is still underdiagnosed and
      incorrectly managed in clinical practice. In particular, only 47% of respondents
      used the validated biochemical parameters to diagnose hyponatraemia secondary to
      SIAD. The survey also indicated a rather satisfactory knowledge of the
      therapeutic options, including the currently available vasopressin receptor
      antagonists. CONCLUSIONS: One of the main findings of the survey was that the
      diagnostic work-up of hyponatraemia still represents a critical issue. Therefore,
      there is urgent need of educational programs in order to improve the management
      of this condition and reduce morbidity, mortality and costs.

PMID- 23558470
TI  - Management of patients with hereditary hemorrhagic telangiectasia undergoing
      general anesthesia: a cohort from a single academic center's experience.
AB  - PURPOSE: Hereditary hemorrhagic telangiectasia is a rare autosomal dominant
      disease characterized by capillary malformation leading to multisite
      cutaneomucosal telangiectasias and multiorgan arteriovenous malformations, which
      can present challenges to anesthetic care. The primary aim of this report is to
      present a large cohort of patients with hereditary hemorrhagic telangiectasia
      undergoing general anesthesia at our institution in regard to comorbid conditions
      and complications of surgical and anesthetic management. METHODS: A computerized
      search from January 1, 2002 through December 31, 2011 of the Mayo Clinic medical
      records database was performed for patients with hereditary hemorrhagic
      telangiectasia who underwent general anesthesia. Medical records were reviewed.
      Eligibility criteria included patients with definite or suspected hereditary
      hemorrhagic telangiectasia based on the Curacao diagnostic criteria who underwent
      general anesthesia during the study period. RESULTS: We identified 74 patients
      with hereditary hemorrhagic telangiectasia who underwent 163 surgeries. The
      majority had pulmonary arteriovenous malformations (56.7%) and iron deficiency
      anemia (64.7%), and high levels of disease burden with a median American Society
      of Anesthesiologist Physical Status score of 3. Most surgeries were related to
      treating conditions associated with hereditary hemorrhagic telangiectasia, with
      the majority being procedures to the nasal mucosa for recurrent epistaxis
      (47.2%). A sizeable proportion of procedures to the nasal mucosa required
      transfusion of blood (12/77). One case of epistaxis required 11 units of blood
      until it was successfully controlled. Another notable complication included
      migration of a coil to pulmonary arteriovenous malformations into the cerebral
      circulation. CONCLUSION: Surgical patients with hereditary hemorrhagic
      telangiectasia often present with multiorgan involvement. The anesthesia provider
      needs to be aware of the high prevalence of pulmonary arteriovenous
      malformations, which may be asymptomatic but can lead to embolic complications.
      Hemorrhage from epistaxis can be severe, and relatively focal procedures to the
      nasal mucosa can require blood transfusions.

PMID- 23558471
TI  - The lumen-facing domain is important for the biological function and organelle-to
      organelle movement of bZIP28 during ER stress in Arabidopsis.
AB  - The membrane-associated transcription factor, bZIP28, is relocated from the
      endoplasmic reticulum (ER) to the Golgi and proteolytically released from the
      membrane mediated by two proteases, S1P and S2P, in response to ER stress in
      Arabidopsis. The activated N-terminal domain recruits nuclear factor Y (NF-Y)
      subunits in the nucleus to regulate ER stress downstream genes. Little is known
      about the functions of the bZIP28 C-terminal lumen-facing domain. Here, we
      provide novel insights into how the ER lumen-facing domain affects the biological
      function and organelle-to-organelle movement of bZIP28 in the ER stress response.
      First, we demonstrated the functional redundancy of bZIP28 and bZIP60 by
      generation and analysis of the bZIP28 and bZIP60 double mutant zip28zip60.
      Subsequent genetic complementation experiments in zip28zip60 background with
      deletions on bZIP28 lumen-facing domain highlighted the importance of lumen
      facing domain for its in vivo function of bZIP28 in the ER stress response. The
      protein subcellular localization and Western blotting results further revealed
      that the bZIP28 lumen-facing domain contains ER retention signal which is
      important for the proteolytic activation of bZIP28. Thus, the bZIP28 lumen-facing
      C-terminus plays important roles in the ER-to-Golgi movement of bZIP28, which may
      contribute to the sensing of the ER stress.

PMID- 23558472
TI  - Detection of minimal residual disease in lung cancer.
AB  - BACKGROUND: Even after successful radical treatment of lung cancer, patients in
      stages I and II of the TNM system very frequently suffer recurrence, which end
      lethally. Detection of subclinical residual disease after surgery is thus one of
      the most important emerging diagnostic methods. Minimal residual disease (MRD) is
      defined as the presence of isolated tumor cells or circulating cells in a patient
      after curative primary tumor removal and at the same time, no clinical signs of
      cancer. Conventional methods cannot detect minimal residual disease and hence
      there is a need for detection using new molecular biological methods. METHODS: We
      searched the PubMed database for original and review articles on minimal residual
      disease in lung cancer. Search words were "lung cancer", "minimal residual
      disease" and "detection of minimal residual disease". The publications we found
      were compared with the results of our own studies on the detection of minimal
      residual disease in lung cancer and the personal experiences are described.
      Examination of blood samples from 98 healthy volunteers and bone marrow from 12
      patients with non inflammatory and non tumour illness, were used to determine cut
      off values for specific markers in the compartments. Subsequently, expression of
      selected markers in tumor tissue was analysed in a pilot sample of 50 patients
      with lung cancer and the presence of MRD was measured as expression of values of
      the tested markers correlated with clinico-pathological characteristics.
      CONCLUSIONS: Recent studies on other malignancies apart from lung cancer have
      shown the importance of MRD detection in the determination of disease progression
      and prognosis. The methods of MRD diagnostics are based on detection of specific
      tumor markers. Of these, the most specific for lung cancer, appears to be the
      LunX protein. The best method for determining MRD is probably RT-PCR. Further
      studies should expand knowledge in this area: to refine understanding of the
      importance of tumor markers for prognosis, as well as to confirm the significance
      of these findings in clinical practice.

PMID- 23558479
TI  - Making sense of the newest information on the dementias.

PMID- 23558473
TI  - Fatal child maltreatment associated with multiple births in Japan: nationwide
      data between July 2003 and March 2011.
AB  - OBJECTIVES: The purpose of the present study is to clarify the impact of multiple
      births in fatal child maltreatment (child death due to maltreatment). METHODS:
      The national annual reports on fatal child maltreatment, which contain all cases
      from July 2003 to March 2011, published by the Ministry of Health, Labor and
      Welfare of Japan, were used as the initial sources of information. Parent-child
      murder-suicide cases were excluded from the analyses. Multiple births, teenage
      pregnancy and low-birthweight were regarded as the exposed groups. The relative
      risks (RRs) and their 95 % confidence intervals (CIs) were estimated using the
      data from the above reports and vital statistics. These analyses were performed
      both including and excluding missing values. RESULTS: Among 437 fatal child
      maltreatment cases, 14 multiple births from 13 families were identified. The RRs
      of multiple births per individual were 1.8 (95 % CI 1.0-3.0) when including
      missing values and 2.7 (95 % CI 1.5-4.8) when excluding missing values. The RRs
      of multiple births per family were 3.6 (95 % CI 2.1-6.2) when including missing
      values and 4.9 (95 % CI 2.7-9.0) when excluding missing values. The RR tended to
      be much lower than the RR of teenage pregnancy (RR 12.9 or 22.2), but slightly
      higher than the RR of low-birthweight (RR 1.4 or 2.9). CONCLUSIONS: Families with
      multiple births had elevated risk for fatal child maltreatment both per
      individual and per family unit. Health providers should be aware that multiple
      pregnancies/births may place significant stress on families and should provide
      appropriate support and intervention.

PMID- 23558480
TI  - Biomarkers of Alzheimer disease: current and future applications to diagnostic
      criteria.
AB  - PURPOSE OF REVIEW: This article reviews recent advances in imaging and fluid
      biomarkers for Alzheimer disease (AD) and their application to newly proposed
      diagnostic criteria across the continuum of AD. RECENT FINDINGS: There have been
      remarkable developments in neuroimaging markers for AD over the past decade, most
      notably the advent of positron emission tomography (PET) amyloid imaging using
      radiotracers that label fibrillar forms of amyloid-beta (Abeta). Similarly, new
      research in CSF markers suggests CSF levels of Abeta1-42 and phosphorylated tau
      may be useful in the early diagnosis of AD and prediction of cognitive decline.
      The National Institute on Aging and the Alzheimer's Association recently convened
      three workgroups to develop joint recommendations for new diagnostic guidelines
      across the spectrum of AD. These recommendations incorporate biomarkers and
      propose updated criteria for the previously recognized stage of AD dementia, the
      evolving definition of mild cognitive impairment, and a newly proposed concept of
      stages of preclinical AD. SUMMARY: Recent advances in AD biomarkers have
      increased the ability to detect evidence of early AD pathology in vivo. These
      biomarkers have been incorporated into new diagnostic recommendations, but a
      number of challenges remain for the biomarkers to become widely applied in
      clinical practice.

PMID- 23558481
TI  - Alzheimer disease pharmacologic treatment and treatment research.
AB  - PURPOSE OF REVIEW: This article reviews marketed pharmacologic treatments for
      Alzheimer disease as well as their efficacy, effectiveness, adverse effects, and
      issues involved in their use, including duration of treatment, adverse events,
      and controversies. Current experimental drug development, including challenges to
      developing successful drugs for Alzheimer disease, are also reviewed and
      assessed. RECENT FINDINGS: Cholinesterase inhibitors and memantine are the
      available pharmacologic treatment options. They show limited clinical effects
      over the shorter term for some patients, mild to moderate cholinergic adverse
      effects in a minority of patients, and potentially underappreciated toxicity over
      the longer term. No subsequent experimental drug in development has been
      successful thus far; there has not been a new drug marketed for Alzheimer disease
      since 2003. SUMMARY: Cholinesterase inhibitors and memantine are marketed for the
      treatment of Alzheimer disease. Drug development programs aimed at new targets,
      including the amyloid-beta cascade, have been unsuccessful thus far despite their
      designs to detect very small or minimal clinical effects from the experimental
      drugs. Marked advances in preclinical science nevertheless support a basis for
      considerable optimism that effective interventions will be found soon.

PMID- 23558483
TI  - Nonpharmacologic treatment and prevention strategies for dementia.
AB  - PURPOSE OF REVIEW: Epidemiologic studies can provide critical evidence to inform
      the timing and duration of nonpharmacologic interventions. Although more studies
      are needed to further determine long-term efficacy, the evidence supporting
      modifiable risk factors for prevention is compelling, and prevention strategies
      that incorporate multidomain nonpharmacologic factors may have the most impact.
      RECENT FINDINGS: Epidemiologic studies have identified a number of promising
      nonpharmacologic factors that have the potential to lower the risk of developing
      dementia. SUMMARY: Potential modifiable strategies for dementia prevention
      include cardiovascular risk factors; lifestyle risk factors such as physical,
      cognitive, and social activity as well as nutrition, smoking, and alcohol use;
      and sleep quality. Results of randomized controlled trials for the treatment of
      cardiovascular risk factors have not been consistent, while interventions that
      increase physical, cognitive, and social activity have demonstrated protective
      effects for dementia risk. Trials of single-nutrient dietary supplementation have
      also been conflicting, but focus on multinutrient supplementation shows promise.
      Observational data also indicate that sleep quality may be a modifiable risk
      factor for dementia prevention.

PMID- 23558484
TI  - The clinical problem of neuropsychiatric signs and symptoms in dementia.
AB  - PURPOSE OF REVIEW: This article reviews behavioral signs and symptoms of dementia
      that can lead to increased mortality, excessive cognitive and functional
      disability, early institutionalization, and increased caregiver burnout. RECENT
      FINDINGS: Almost all patients with a dementia will develop significant behavioral
      disturbances at some point over the course of their illness. These behavioral
      signs and symptoms rarely fit into usual diagnostic classifications or meet full
      criteria for a formal major psychiatric disorder. SUMMARY: Treatment of
      behavioral signs and symptoms of dementia should include both pharmacologic and
      nonpharmacologic interventions. There are currently no treatments for these
      disturbances approved by the US Food and Drug Administration. Best judgment
      should be used in identifying dominant target symptoms and matching them to the
      most relevant drug class. Implementing nonpharmacologic interventions before the
      development of neuropsychiatric symptoms may prevent triggers related to a
      progressively lowered stress threshold and therefore is key in the treatment of
      all patients with a dementia.

PMID- 23558482
TI  - New genes and new insights from old genes: update on Alzheimer disease.
AB  - PURPOSE OF REVIEW: This article discusses the current status of knowledge
      regarding the genetic basis of Alzheimer disease (AD) with a focus on clinically
      relevant aspects. RECENT FINDINGS: The genetic architecture of AD is complex, as
      it includes multiple susceptibility genes and likely nongenetic factors. Rare but
      highly penetrant autosomal dominant mutations explain a small minority of the
      cases but have allowed tremendous advances in understanding disease pathogenesis.
      The identification of a strong genetic risk factor, APOE, reshaped the field and
      introduced the notion of genetic risk for AD. More recently, large-scale genome
      wide association studies are adding to the picture a number of common variants
      with very small effect sizes. Large-scale resequencing studies are expected to
      identify additional risk factors, including rare susceptibility variants and
      structural variation. SUMMARY: Genetic assessment is currently of limited utility
      in clinical practice because of the low frequency (Mendelian mutations) or small
      effect size (common risk factors) of the currently known susceptibility genes.
      However, genetic studies are identifying with confidence a number of novel risk
      genes, and this will further our understanding of disease biology and possibly
      the identification of therapeutic targets.

PMID- 23558485
TI  - The diagnostic evaluation of a patient with dementia.
AB  - PURPOSE OF REVIEW: This review outlines a practical approach to the history,
      mental state, neurologic examination, and laboratory tests in the diagnosis of
      dementia. RECENT FINDINGS: Proposed new diagnostic criteria for Alzheimer disease
      recognize that nonamnestic presentations with symptoms that predominantly affect
      language, visuospatial abilities, or executive function may occur, particularly
      with onset before the age of 65. New criteria assign greater likelihood to
      diagnosis if progressive cognitive decline is documented through serial
      assessment, or if biomarkers are supportive. In patients aged 80 or older, more
      than one cause of dementia is often present, for example, Alzheimer disease plus
      vascular dementia. Clinical diagnostic criteria for non-Alzheimer dementias are
      evolving, particularly in areas such as frontotemporal dementia. Imaging and CSF
      biomarkers have been proposed in recent diagnostic criteria for Alzheimer
      disease. Although biomarkers can provide a higher level of certainty that
      Alzheimer pathology may or may not be present, biomarkers for non-Alzheimer
      dementias are lacking. SUMMARY: The availability of biomarkers does not replace
      or diminish the need for a thorough clinical evaluation. A structured clinical
      approach helps to define the diagnosis and collects information essential for
      establishing a comprehensive care plan for patients with dementia and their
      families.

PMID- 23558486
TI  - Mild cognitive impairment.
AB  - PURPOSE OF REVIEW: The term mild cognitive impairment (MCI) is used to describe
      older subjects with demonstrable cognitive impairment who have not crossed the
      threshold for dementia. Because patients with MCI have an increased risk of
      developing dementia, especially Alzheimer disease (AD), there is significant
      interest in the clinical characterization of these subjects and in understanding
      the pathophysiology of the transition from MCI to AD. RECENT FINDINGS: The MCI
      syndrome, as an expression of an incipient disorder that may lead to dementia, is
      extremely heterogeneous and may coexist with systemic, neurologic, or psychiatric
      disorders that can cause cognitive deficits. Recent clinical criteria were
      designed to take into account the different forms of clinical presentation of the
      syndrome, and introduced the possible contribution of biomarkers to the clinical
      diagnosis. Bedside diagnosis of MCI can be difficult, since patients who report
      having cognitive problems may have normal scores in global cognitive scales or in
      brief neuropsychological instruments. SUMMARY: This article presents the
      evolution of the clinical concept of MCI, the operationalization of its current
      definitions, the development of biomarkers that can help to identify an
      underlying neurodegenerative process as the etiology of the syndrome, and its
      proposed treatments.

PMID- 23558487
TI  - Understanding and treating vascular cognitive impairment.
AB  - PURPOSE OF REVIEW: It is estimated that one in three people will experience a
      stroke, dementia, or both during their lifetime. The goal of this article is to
      assist clinicians in the identification and treatment of patients with vascular
      cognitive impairment (VCI). To that end, we will discuss the scope and definition
      of VCI; how this definition can be applied in clinical practice; VCI epidemiology
      and pathogenesis, its clinical features, and assessment; and prevention and
      treatment of this disorder. RECENT FINDINGS: During the past decade, we have
      gained a more complete understanding of clinical manifestations of VCI (eg, the
      importance of executive function and memory), what it looks like pathologically
      (eg, the role of cerebral amyloid angiopathy, microinfarcts, and "silent"
      strokes), and how VCI relates to other disease processes (eg, co-occurrence with
      Alzheimer disease). A recent American Heart Association and American Stroke
      Association guidance statement clarified the construct of VCI, including the
      severity of cognitive and behavioral dysfunction contained under the definition
      of VCI and the presence of both "pure" and "mixed" VCI forms. VCI treatments
      approved by the US Food and Drug Administration are still lacking, and challenges
      remain regarding how to convert promising observational study findings that link
      stroke and coronary heart disease risk factors to cognitive impairment and
      dementia into evidence-based preventive methods. SUMMARY: VCI is a common
      contributor to cognitive impairment in later life. Because the risk of Alzheimer
      disease may be heightened by the same risk factors that make us susceptible to
      stroke and coronary heart disease, these borderlands merit careful consideration
      as we strive to preserve cognitive function throughout the aging process.

PMID- 23558488
TI  - Incorporating new diagnostic schemas, genetics, and proteinopathy into the
      evaluation of frontotemporal degeneration.
AB  - PURPOSE OF REVIEW: Within the continuously growing body of knowledge in the field
      of dementia, frontotemporal degeneration stands out in importance as the second
      most common cause of early-onset dementia after Alzheimer disease. Neurologists,
      neuropsychologists, and speech pathologists are particularly involved in the
      diagnosis and recognition of etiologies for patients with deficits in frontal
      lobe function and language. RECENT FINDINGS: The recent discovery of a novel
      mutant gene (C9ORF72) and the new nomenclature adopted for subclassification have
      significantly promoted our understanding of this disorder. SUMMARY: This article
      relates the most recent consensus criteria for diagnosis of the two forms of
      frontotemporal degeneration (ie, behavioral and primary progressive aphasia
      variants) to basic neurologic principles and remind clinicians of the
      neuropsychiatric and neuroradiologic components that clarify frontotemporal
      degeneration diagnoses and guide management.

PMID- 23558490
TI  - "Will I get Alzheimer disease?" when cognitively normal patients ask to be tested
      for Alzheimer disease.
AB  - This article presents the case of a cognitively normal patient who is requesting
      a procedure (amyloid imaging) recently approved for the diagnosis of Alzheimer
      disease (AD) in patients with cognitive impairment. The predictive value of this
      test in unaffected people is not clearly established. Knowing the results of the
      test will have no effect on therapeutic options, although the patient may make
      lifestyle decisions based on the results. There is potential risk to the patient
      in terms of insurability, employability, and psychological consequences.
      Physicians will face this situation with increasing frequency as the AD biomarker
      field progresses.

PMID- 23558489
TI  - Dementia in the oldest old.
AB  - PURPOSE OF REVIEW: This article discusses some of the unique features of dementia
      in the oldest old, including some of the most common diagnostic challenges, and
      potential strategies to overcome them. RECENT FINDINGS: Advances include new
      insight into the role of common risk factors and the effects of multiple
      underlying neuropathologic features for dementia in the oldest old. In addition,
      this article contains the latest age-specific normative data for commonly used
      neuropsychological tests for the oldest old. SUMMARY: The oldest old-people aged
      90 years and older-are the fastest-growing segment of society and have the
      highest rates of dementia in the population. The risk factors, diagnostic
      challenges, and underlying neuropathologic features of dementia are strikingly
      different in the 90-years-and-older population compared to younger elderly.
      Special consideration of these unique features of dementia is necessary when
      evaluating oldest-old subjects with cognitive impairment.

PMID- 23558491
TI  - Genetic testing for early-onset Alzheimer disease.
AB  - The availability of testing for identified risk genes for Alzheimer disease (AD)
      in patients with clinically probable AD or their at-risk family members raises
      important questions for the neurologist. Because the potential benefits and risks
      of testing vary for each patient, physicians need to evaluate whether it is
      appropriate on a case-by-case basis. This article outlines the testing decision
      process and serves as a guide to assist clinicians with associated counseling and
      result disclosure. Because genetic testing is relatively new and preventive and
      therapeutic options for AD remain limited, it is important to remain sensitive to
      and understand the specific challenges associated with obtaining these tests in
      the routine clinical setting.

PMID- 23558494
TI  - Multiple-choice questions.

PMID- 23558492
TI  - Coding for behavioral neurology.

PMID- 23558496
TI  - Patient management problem.

PMID- 23558499
TI  - Leading the solution.

PMID- 23558500
TI  - Creating accurate models of life.

PMID- 23558501
TI  - Mutual enlightenment.

PMID- 23558502
TI  - Clinical ethical concerns in the implantation of brain-machine interfaces.

PMID- 23558503
TI  - James Clerk Maxwell, Kirchhoff's Laws, and their implications on modeling
      physiology.

PMID- 23558504
TI  - Highly selective Wacker reaction of styrene derivatives: a green and efficient
      aerobic oxidative process promoted by benzoquinone/NaNO2/HClO4 under mild
      conditions.
AB  - A green and efficient catalytic redox system for the aerobic oxidative Wacker
      oxidation of styrene derivatives at room temperature using molecular oxygen as
      the terminal oxidant without copper chloride has been developed. The newly
      developed system exhibited excellent catalytic activity for the smooth
      transformation of terminal styrene derivatives to the desired methyl ketones with
      up to 96% yield and >99% selectivity.

PMID- 23558505
TI  - Public acceptance of euthanasia in Europe: a survey study in 47 countries.
AB  - OBJECTIVES: In recent years, the European euthanasia debate has become more
      intense, and the practice was legalized in the Netherlands, Belgium, and
      Luxembourg. We aimed to determine the current degree of public acceptance of
      euthanasia across Europe and investigate what factors explain differences.
      METHODS: Data were derived from the 2008 wave of the European Values Survey
      (EVS), conducted in 47 European countries (N = 67,786, response rate = 69 %).
      Acceptance of euthanasia was rated on a 1-10 scale. RESULTS: Relatively high
      acceptance was found in a small cluster of Western European countries, including
      the three countries that have legalized euthanasia and Denmark, France, Sweden
      and Spain. In a large part of Europe public acceptance was relatively low to
      moderate. Comparison with the results of the previous EVS wave (1999) suggests a
      tendency towards a polarization in Europe, with most of Western Europe becoming
      more permissive and most of Eastern Europe becoming less permissive. CONCLUSIONS:
      There is roughly a West-East division in euthanasia acceptance among the European
      public, making a pan-European policy approach to the issue difficult.

PMID- 23558506
TI  - Diabetes-free survival in patients who underwent islet autotransplantation after
      50% to 60% distal partial pancreatectomy for benign pancreatic tumors.
AB  - BACKGROUND: Several retrospective studies with short-term follow-up have
      demonstrated a low rate of new-onset diabetes after distal pancreatectomy for
      benign pancreatic tumors. We sought to determine the long-term diabetes-free
      survival of patients who underwent islet autotransplantation (IAT) after distal
      pancreatectomy and to identify any associations between the isolation parameters
      of autologous islets and diabetes-free survival. METHODS: Among the 37
      nondiabetic patients who underwent 50% to 60% partial pancreatectomy, 20
      underwent IAT (IAT group; median follow-up period, 61 months). In the IAT group,
      diabetes-free survival was determined based on annual oral glucose tolerance
      tests, fasting blood glucose, and hemoglobin A1C. RESULTS: The 7-year diabetes
      free survival rate was 51% in the IAT group (median follow-up period, 61 months)
      and 45% in the 37 study subjects. Diabetes-free survival was significantly
      prolonged when islet yield per gram of pancreas weight was more than 5154 islet
      equivalents (IEQ)/g, even in patients with prediabetes and high insulin
      resistance who had a markedly high rate of diabetes development. The proportion
      of patients with impaired glucose tolerance at 2 years after distal
      pancreatectomy was 12 of 16 in the control group, 6 of 7 in patients with islet
      yields of less than 5154 IEQ/g, and 3 of 11 in patients with islet yields of more
      than 5154 IEQ/g (P=0.019). CONCLUSIONS: Partial (50%-60%) pancreatectomy for
      benign pancreatic tumors had a major metabolic consequence, especially in
      patients with prediabetes and high insulin resistance. In this setting, prolonged
      diabetes-free survival was observed in patients who underwent IAT when a high
      islet yield per gram of pancreas was achieved.

PMID- 23558507
TI  - Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant
      recipients: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Although mycophenolate mofetil (MMF) is recommended at a fixed dose,
      there is increasing interest in controlled-dose (CD) MMF based on therapeutic
      drug monitoring. We systematically evaluated published randomized controlled
      trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney
      transplant recipients. METHODS: The electronic databases Medline, Embase, and
      Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two
      reviewers independently applied the study selection criteria, examined the study
      quality, and extracted the data. Dichotomous measures were expressed as relative
      risk (RR) and continuous outcomes were expressed as weighted mean difference,
      both with 95% confidence intervals (CIs). All statistical analyses were performed
      using Review Manager 5.1.6. RESULTS: Four RCTs met our selection criteria and
      included 1755 de novo recipients. The differences between CD and fixed-dose MMF
      in treatment failure (RR, 0.95; 95% CI, 0.82-1.10; P=0.52), serum creatinine
      clearance (weighted mean difference, 2.46; 95% CI, -1.15 to 6.07; P=0.18), total
      gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65-2.35; P=0.53), diarrhea
      (RR, 1.08; 95% CI, 0.92-1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95-1.64;
      P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93-1.35; P=0.25), thrombocytopenia (RR,
      0.80; 95% CI, 0.47-1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27-1.38;
      P=0.23) were not statistically significant. Furthermore, total infections were
      more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03-1.30;
      P=0.01). CONCLUSIONS: Based on current evidence, CD MMF administration cannot be
      recommended as routine practice for kidney transplant recipients. Therapeutic
      drug monitoring for MMF may be targeted toward high-risk recipients, who should
      be identified in future studies.

PMID- 23558508
TI  - Iranian 2012 earthquake: the importance of Focused Assessment with Sonography for
      Trauma (FAST) in assessing a huge mass of injured people.

PMID- 23558509
TI  - Assessment of S values in stylized and voxel-based rat models for positron
      emitting radionuclides.
AB  - PURPOSE: Positron emission tomography (PET) is a powerful tool in small animal
      research, enabling noninvasive quantitative imaging of biochemical processes in
      living subjects. However, the dosimetric characteristics of small animal PET
      imaging are usually overlooked, although the radiation dose may be significant.
      The variations of anatomical characteristics between the various computational
      models may result in differences in the dosimetric outcome. METHODS: We used five
      different anatomical rat models (two stylized and three voxel based) to compare
      calculated absorbed fractions and S values for eight positron-emitting
      radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Y-86, and I-124) commonly
      used to label various probes for small animal PET imaging. The MCNPX radiation
      transport code was used for radiation dose calculations. RESULTS: For most
      source/target organ pairs, O-15 and Ga-68 produce the highest self-absorbed S
      values because of the high-energy and high-frequency of positron emissions, while
      Y-86 produces the highest cross-absorbed S values because of the high energy and
      high frequency of gamma-rays emission. Anatomical models produced from different
      rat strains or modeling techniques exhibit different organ masses, volumes, and
      thus give rise to different S values and absorbed dose. The variations of
      absorbed fractions between models of the same type are less than those between
      models with different types. The calculated S values depend strongly on organ
      mass, and as such, different models produce similar S values for organs of
      comparable masses. In most source organs presenting with high cumulated activity,
      the absorbed dose is less affected by model difference compared with other
      organs. CONCLUSIONS: The produced S values for common positron-emitting
      radionuclides can be exploited in the assessment of radiation dose to rats from
      different radiotracers used in small animal PET experiments. This work
      contributes to a better understanding of the influence of different computational
      models on small animal dosimetry.

PMID- 23558510
TI  - Monitoring hemodynamic and morphologic responses to closed head injury in a mouse
      model using orthogonal diffuse near-infrared light reflectance spectroscopy.
AB  - The authors' aim is to assess and quantitatively measure brain hemodynamic and
      morphological variations during closed-head injury (CHI) in mice using orthogonal
      diffuse near-infrared reflectance spectroscopy (o-DRS). CHI is a type of injury
      to the head that does not penetrate the skull. Usually, it is caused by
      mechanical blows to the head and frequently occurs in traffic accidents, falls,
      and assaults. Measurements of brain optical properties, namely absorption and
      reduced scattering coefficients in the wavelength range from 650 to 1000 nm were
      carried out by employing different source-detector distance and locations to
      provide depth sensitivity on an intact scalp over the duration of the whole
      experiment. Furthermore, alteration in both cortical hemodynamics and morphologic
      markers, i.e., scattering power and amplitude properties were derived. CHI was
      induced in anesthetized male mice by a weight-drop model using ~50 g cylindrical
      metal falling from a height of 90 cm onto the intact scalp producing an impact of
      4500 g cm. With respect to baseline, difference in brain physiological properties
      was observed following injury up to 1 h post-trauma. Additionally, the reduced
      scattering spectral shapes followed Mie scattering theory was quantified and
      clearly shows changes in both scattering amplitude and power from baseline
      indicating structural variations likely from evolving cerebral edema during CHI.
      We further demonstrate high correlation between scattering amplitude and
      scattering power, with more than 20% difference in slope in comparison to
      preinjury. This result indicates the possibility of using the slope also as a
      marker for detection of structural changes. Finally, experiments investigating
      brain function during the first 20 min postinjury were conducted and changes in
      chromophore concentrations and scattering were observed. Overall, our experiments
      demonstrate the potential of using the proposed technique as a valuable
      quantitative noninvasive tool for monitoring brain physiology following CHI
      injury at the bedside and/or at the field.

PMID- 23558511
TI  - Plastic protein microarray to investigate the molecular pathways of magnetic
      nanoparticle-induced nanotoxicity.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) (about 15 nm) were
      synthesized via a hydrothermal method and characterized by field emission
      scanning electron microscopy, transmission electron microscopy, dynamic light
      scattering, x-ray diffraction, and vibrating sample magnetometer. The molecular
      pathways of SPIONs-induced nanotoxicity was further investigated by protein
      microarrays on a plastic substrate from evaluation of cell viability, reactive
      oxygen species (ROS) generation and cell apoptosis. The experimental results
      reveal that 50 MUg ml(-1) or higher levels of SPIONs cause significant loss of
      cell viability, considerable generation of ROS and cell apoptosis. It is proposed
      that high level SPIONs could induce cell apoptosis via a mitochondria-mediated
      intrinsic pathway by activation of caspase 9 and caspase 3, an increase of the
      Bax/Bcl-2 ratio, and down-regulation of HSP70 and HSP90 survivor factors.

PMID- 23558512
TI  - Electrogenic proton transport across lipid bilayer membranes mediated by cationic
      derivatives of rhodamine 19: comparison with anionic protonophores.
AB  - Protonophores can be considered as candidates for anti-obesity drugs and tools to
      prevent excessive reactive oxygen species production in mitochondria by means of
      a limited decrease in the mitochondrial potential. Experimentally used
      protonophores are weak acids that can carry protons across a membrane in a
      neutral (protonated) form, and they come back in an anionic (deprotonated) form.
      A cationic derivative of rhodamine 19 and plastoquinone (SkQR1) was recently
      shown to possess uncoupling activity in mitochondria and in intact cells. In this
      article, we studied the mechanism of action of SkQR1 and its plastoquinone
      lacking analog (C12R1) on a planar bilayer lipid membrane by applying voltage
      jumps. The steady-state current was proportional to the C12R1 concentration in a
      manner as if the monomeric form of the carrier were operative. As predicted by
      the carrier model, at high pH, when rhodamines were mainly deprotonated, the
      current changed immediately following a jump in the applied potential and then
      remained constant. By contrast, at low pH, the current relaxed from an initially
      high value to a lower value since the protonated carrier cations were
      redistributed in the membrane. An inverse pH dependence was revealed with the
      anionic protonophore CCCP. The dependence of the SkQR1 protonophorous activity on
      voltage exhibited an increase at high voltages, an effect that might facilitate
      mild (self-limited) uncoupling of mitochondria.

PMID- 23558513
TI  - Phase 2 study of S-1 and carboplatin plus bevacizumab followed by maintenance S-1
      and bevacizumab for chemotherapy-naive patients with advanced nonsquamous non
      small cell lung cancer.
AB  - BACKGROUND: A previous phase 3 trial demonstrated noninferiority in terms of
      overall survival for combined S-1 (an oral fluoropyrimidine) and carboplatin
      compared with combined paclitaxel and carboplatin as first-line treatment for
      advanced non-small cell lung cancer (NSCLC). In the current study, the authors
      evaluated the efficacy and safety of combined S-1, carboplatin, and bevacizumab
      followed by maintenance with S-1 and bevacizumab in chemotherapy-naive patients
      with advanced nonsquamous NSCLC. METHODS: Patients received carboplatin (area
      under the concentration-time curve, 5 mg mL(-1) per minute) and bevacizumab (15
      mg/kg) on day 1 plus oral S-1 (80 mg/m2 per day) on days 1 through 14 every 21
      days for up to 6 cycles. For patients without disease progression, S-1 and
      bevacizumab were continued until disease progression or unacceptable toxicity
      developed. RESULTS: Forty-eight patients were enrolled in the phase 2 study; of
      these, 35 patients (72.9%) completed at least 4 cycles. Most toxicities of grade
      >=3 were hematologic, and no increase in relative incidence associated with
      maintenance with S-1 and bevacizumab was observed. The objective response rate
      was 54.2% (95% confidence interval, 39.2%-68.6%), and the median progression-free
      survival was 6.8 months (95% confidence interval, 4.3-8.2 months). CONCLUSIONS:
      The regimen of combined S-1, carboplatin, and bevacizumab followed by maintenance
      with S-1 and bevacizumab was active and feasible as first-line treatment for
      advanced nonsquamous NSCLC.

PMID- 23558514
TI  - Docetaxel-loaded solid lipid nanoparticles: preparation, characterization, in
      vitro, and in vivo evaluations.
AB  - The aim of the present study was to prepare, characterize, and evaluate solid
      lipid nanoparticles (SLNs) containing docetaxel (DTX) to improve the efficacy of
      this chemotherapeutic agent. SLNs containing DTX (SLN-DTX) were prepared by
      microemulsion and probe sonication techniques. In vitro cytotoxicity of SLN-DTX
      compared with Taxotere(r) (TXT) was evaluated on colorectal (C-26) and malignant
      melanoma (A-375) cell lines. Cellular uptake experiment was also carried out on C
      26 cells. In in vivo tests, tumor inhibitory efficacy and survival were compared
      with TXT on C-26-implanted BALB/c mice. SLN-DTX particle size was 180 nm and PDI
      of 0.2 with spherical shape. Encapsulation efficacy was more than 98%. SLN-DTX at
      concentration of 100 MUM caused 100% and 99.9% viability reduction in C-26 and A
      375 after 48 and 72 h, respectively. The half maximal inhibitory concentration
      (IC50 ) of SLN-DTX on C-26 and A-375 was respectively 0.769 and 28.132 MUM after
      24 h. DTX cell uptake from SLN-DTX was remarkably higher than TXT. SLN-DTX showed
      better tumor inhibitory efficacy and survival at a dose of 10 mg/kg versus 10 and
      20 mg/kg TXT. In conclusion, the results of the present study showed that the
      efficacy of SLN-DTX was better than TXT in cell-uptake and in vivo experiments.

PMID- 23558515
TI  - Low-lying excited-states of 5-benzyluracil.
AB  - A numerical study is reported concerning the first and second singlet excited
      states of 5-benzyluracil using the multireference self-consistent field (state
      averaged CASSCF) method. The vertical excitation energies of low-lying excited
      states were characterized using the SA-CASSCF method, as well as using higher
      level methods, such as CASPT2, MRCI and EOM-CCSD. The local minima and conical
      intersections found on the potential energy surfaces (PESs) were characterized in
      terms of molecular geometry and natural population analysis. Different relaxation
      pathways on the PESs are identified and discussed by comparing with the similar
      pathways found for the individual monomers of uracil and benzene. The molecule
      can be thought of as a model system for the study of crosslink reaction between
      DNA and proteins induced by UV light.

PMID- 23558516
TI  - An evidence-based consensus for the classification of arbuscular mycorrhizal
      fungi (Glomeromycota).
AB  - The publication of a large number of taxon names at all levels within the
      arbuscular mycorrhizal fungi (Glomeromycota) has resulted in conflicting
      systematic schemes and generated considerable confusion among biologists working
      with these important plant symbionts. A group of biologists with more than a
      century of collective experience in the systematics of Glomeromycota examined all
      available molecular-phylogenetic evidence within the framework of phylogenetic
      hypotheses, incorporating morphological characters when they were congruent. This
      study is the outcome, wherein the classification of Glomeromycota is revised by
      rejecting some new names on the grounds that they are founded in error and by
      synonymizing others that, while validly published, are not evidence-based. The
      proposed "consensus" will provide a framework for additional original research
      aimed at clarifying the evolutionary history of this important group of symbiotic
      fungi. 

PMID- 23558517
TI  - Frost hardiness of mycorrhizal (Hebeloma sp.) and non-mycorrhizal Scots pine
      roots.
AB  - The frost hardiness (FH) of mycorrhizal [ectomycorrhizal (ECM)] and non
      mycorrhizal (NM) Scots pine (Pinus sylvestris) seedlings was studied to assess
      whether mycorrhizal symbiosis affected the roots' tolerance of below-zero
      temperatures. ECM (Hebeloma sp.) and NM seedlings were cultivated in a growth
      chamber for 18 weeks. After 13 weeks' growth in long-day and high-temperature
      (LDHT) conditions, a half of the ECM and NM seedlings were moved into a chamber
      with short-day and low-temperature (SDLT) conditions to cold acclimate. After
      exposures to a range of below-zero temperatures, the FH of the roots was assessed
      by means of the relative electrolyte leakage test. The FH was determined as the
      inflection point of the temperature-response curve. No significant difference was
      found between the FH of mycorrhizal and non-mycorrhizal roots in LDHT (-8.9 and 
      9.8  degrees C) or SDLT (-7.5 and -6.8  degrees C). The mycorrhizal treatment had
      no significant effect on the total dry mass, the allocation of dry mass among the
      roots and needles or nutrient accumulation. The mycorrhizal treatment with
      Hebeloma sp. did not affect the FH of Scots pine in this experimental setup. More
      information is needed on the extent to which mycorrhizas tolerate low
      temperatures, especially with different nutrient contents and different
      mycorrhiza fungi. 

PMID- 23558518
TI  - Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical
      studies.
AB  - The development of safer drugs is a high priority for pharmaceutical companies.
      Among the various toxicities caused by drugs, cardiotoxicity is an important
      issue because of its lethality. In addition, cardiovascular toxicity leads to the
      attrition of many drug candidates in both preclinical and clinical phases.
      Although histopathological and blood chemistry examinations are the current gold
      standards for detecting cardiotoxicity in preclinical studies, the large number
      of withdrawals from clinical studies owing to safety problems indicate that a
      more sensitive tool is required. We recently identified 32 genes that were
      candidate genomic biomarkers for cardiotoxicity in rats. Based on their
      functions, the present study focused on 8 of these 32 genes (Spp1, Fhl1, Timp1,
      Serpine1, Bcat1, Lmcd1, Rnd1 and Tgfb2). Diagnostic accuracy for the genes was
      determined by a receiver-operating characteristic (ROC) analysis using more
      cardiotoxic and non-cardiotoxic compounds. In addition, an optimized support
      vector machine (SVM) model that was composed of Spp1 and Timp1 was newly
      constructed. This new multi-gene model exhibited a much higher diagnostic
      accuracy than that observed for plasma cardiac troponin I (cTnI), which is one of
      the most useful plasma biomarkers for cardiotoxicity detection. Furthermore, we
      determined that this multi-gene model could predict potential cardiotoxicity in
      rats in the absence of any cardiac histopathological lesions or elevations of
      plasma cTnI. Overall, this multi-gene model exhibited advantages over classic
      tools commonly used for cardiotoxicity evaluations in rats. Our current results
      suggest that application of the model could potentially lead to the production of
      safer drugs.

PMID- 23558519
TI  - Risk factors for deep infection after total knee arthroplasty: a meta-analysis.
AB  - OBJECTIVE: Estimated the risk factors for postoperative infection after total
      knee arthroplasty (TKA) to prevent its occurrence. DESIGN: The meta-analysis
      collected twelve cohorts or case-control studies which included 548 infected
      persons in 57,223 general cases. Review Manager 5.0 was operated to assess the
      heterogeneity and to give an overall estimate of the association of factors with
      postoperative infection after TKA. RESULTS: The main factors distinctly
      associated with infection after TKA were BMI (BMI >30: OR = 2.53, 95 % CI 1.25,
      5.13; BMI >40: OR = 4.00, 95 % CI 1.23, 12.98), diabetes mellitus (OR = 3.72, 95
      % CI 2.30, 6.01), hypertension (OR = 2.53, 95 % CI 1.07, 5.99), steroid therapy
      (OR = 2.04, 95 % CI 1.11, 3.74), and rheumatoid arthritis (OR = 1.83; 95 % CI
      1.42, 2.36). It had no sufficient evidences to reveal that gender could lead to
      infection after TKA. Osteoarthritis appeared to have a moderately protective
      effect. Statistical analysis revealed no correlation between urinary tract
      infection, fixation method, ASA, bilateral operation, age, transfusion,
      antibiotics, bone graft, and infection. CONCLUSION: There were positive evidences
      for some certain factors which could be targeted for prevention of the onset of
      infection, but more studies are needed to define the association of some other
      controversial factors in infection, like osteoarthritis, gender and so on. The
      quality of studies also needs to be improved.

PMID- 23558520
TI  - Radio-lunate arthrodesis in rheumatoid arthritis: outcome and techniques.
AB  - BACKGROUND AND PURPOSE: The wrist is one of the most affected joints in
      rheumatoid arthritis. The purpose of this retrospective study was to assess
      clinical, functional and radiographic results of radio-lunate arthrodesis. Two
      different operation and fixation techniques are compared and detailed outcome
      after this intervention is presented. METHODS: Twenty-seven patients with long
      standing rheumatoid arthritis were operated on, either by stabilisation of the
      arthrodesis with Shapiro staples (n = 14) or by Herbert screw (n = 13) and
      followed for a mean of 5.4 years. RESULTS: Radio-lunate arthrodesis resulted in
      high overall and subjective satisfaction concerning function, grip and return to
      work. Grip strength was 35 kPa for the dominant and 26 kPa for the non-dominant
      hand. No revision, pseudoarthrosis or hardware failure was observed; only two
      conservatively treated wound healing problems were reported. The procedure
      resulted in a mean flexion of 26 degrees  and a mean extension of 24 degrees ; a
      clear improvement was also seen in activities of daily life. No difference
      between both groups was observed for pain, complication rate or functional
      outcome. INTERPRETATION: Due to high patient satisfaction and functional outcome,
      radio-lunate wrist arthrodesis can be recommended independent of fixation method.

PMID- 23558521
TI  - Personalized management of essential thrombocythemia-application of recent
      evidence to clinical practice.
AB  - The World Health Organization (WHO) classification system has recently
      strengthened the diagnostic criteria for essential thrombocythemia (ET) by
      lowering the threshold platelet count, underscoring its morphological distinction
      from early/prefibrotic myelofibrosis (MF) and incorporating molecular markers of
      clonality. The International Working Group for Myeloproliferative Neoplasms
      Research and Treatment (IWG-MRT) examined the clinical relevance of this process
      in 1104 cases of locally diagnosed 'ET' and showed worse overall, leukemia-free
      and fibrosis-free survival, and a higher risk of bleeding in early/prefibrotic MF
      (n=180) vs WHO-defined ET (n=891). The risk of thrombosis was similar between the
      two entities and, in WHO-defined ET, was predicted by thrombosis history, older
      age, cardiovascular risk factors and JAK2V617F. A prognostic model based on these
      risk factors identified patient groups in ET with residual risk of thrombosis,
      despite treatment with conventional therapy. The main objectives of the current
      perspective are to underscore the prognostic importance of morphological
      confirmation in the diagnosis of ET and provide management recommendations, in
      both WHO-defined ET and early/prefibrotic MF, based on observations from the
      aforementioned IWG-MRT and other studies. In so doing, we are fully cognizant and
      sympathetic of the fact that some of our recommendations need to be tested in
      prospective controlled studies. 

PMID- 23558522
TI  - An evolutionary perspective on chronic myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) shares with other myeloid diseases a
      number of somatic gene mutations. These mutations can now be integrated within
      the framework of evolution theory to address the mechanisms of the disease.
      Several evidences indicate that the disease emerges in adult hematopoietic stem
      cells (HSC) through the age-dependent accumulation of DNA damage, leading
      stochastically to a driver mutation that confers a competitive advantage to the
      cell. A mutation in TET2 gene could be one of these driver mutations provoking
      the emergence of clonality. After a long latency, secondary lesions, such as
      mutations in the SRSF2 gene, contribute to progression to full-blown malignancy,
      with abnormal differentiation. Additional mutations accumulate and branching
      arising mostly through mitotic recombination generates clonal heterogeneity.
      Modifications in the microenvironment probably affect this clonal dynamics,
      whereas epigenetic alterations, such as hypermethylation of the TIF1gamma gene
      promoter, may generate phenotypic diversification of otherwise clonal
      populations. The preserved although deregulated myeloid differentiation that
      characterizes CMML, with granulomonocyte expansion and various cytopenias, may
      depend on early clonal dominance in the hematopietic cell hierarchy. Progression
      to acute myeloid leukemia observed in 25-30% of the patients may arise from the
      massive expansion of a clone with novel genetic lesions, providing a high fitness
      to previously minor subclones when in chronic phase of the disease. This review
      discusses the various models of disease emergence and progression and how this
      recent knowledge could drive rational therapeutic strategies. 

PMID- 23558523
TI  - SETBP1 mutations in 415 patients with primary myelofibrosis or chronic
      myelomonocytic leukemia: independent prognostic impact in CMML.

PMID- 23558525
TI  - Consolidation with VTd significantly improves the complete remission rate and
      time to progression following VTd induction and single autologous stem cell
      transplantation in multiple myeloma.

PMID- 23558524
TI  - Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets
      of chronic lymphocytic leukemia: the case of SF3B1 and subset #2.
AB  - Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3
      genes in chronic lymphocytic leukemia (CLL), especially among aggressive,
      chemorefractory cases. Nevertheless, it is currently unknown whether their
      presence may differ in subsets of patients carrying stereotyped B-cell receptors
      and also exhibiting distinct prognoses. Here, we analyzed the mutation status of
      NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that
      is, subset #1, #2 and #8, aiming to explore links between genetic aberrations and
      immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed
      in subset #2 (44%) versus subset #1 and #8 (4.6% and 0%, respectively; P<0.001).
      In contrast, the frequency of NOTCH1 mutations in subset #2 was only 8%, lower
      than the frequency observed in either subset #1 or #8 (19% and 14%, respectively;
      P=0.04 for subset #1 versus #2). No associations were found for BIRC3 mutations
      that overall were rare. The apparent non-random association of certain mutations
      with stereotyped CLL subsets alludes to subset-biased acquisition of genomic
      aberrations, perhaps consistent with particular antigen/antibody interactions.
      These novel findings assist in unraveling specific mechanisms underlying clinical
      aggressiveness in poor-prognostic stereotyped subsets, with far-reaching
      implications for understanding their clonal evolution and implementing
      biologically oriented therapy. 

PMID- 23558526
TI  - A role for reactive oxygen species in JAK2 V617F myeloproliferative neoplasm
      progression.
AB  - Although other mutations may predate the acquisition of the JAK2(V617F) mutation,
      the latter is sufficient to drive the disease phenotype observed in BCR-ABL
      negative myeloproliferative neoplasms (MPNs). One of the consequences of
      JAK2(V617F) is genetic instability that could explain JAK2(V617F)-mediated MPN
      progression and heterogeneity. Here, we show that JAK2(V617F) induces the
      accumulation of reactive oxygen species (ROS) in the hematopoietic stem cell
      compartment of a knock-in (KI) mouse model and in patients with JAK2(V617F) MPNs.
      JAK2(V617F)-dependent ROS elevation was partly mediated by an AKT-induced
      decrease in catalase expression and was accompanied by an increased number of 8
      oxo-guanines and DNA double-strand breaks (DSBs). Moreover, there was evidence
      for a mitotic recombination event in mice resulting in loss of heterozygosity of
      Jak2(V617F). Mice engrafted with 30% of Jak2(V617F) KI bone marrow (BM) cells
      developed a polycythemia vera-like disorder. Treatment with the anti-oxidant N
      acetylcysteine (NAC) substantially restored blood parameters and reduced damages
      to DNA. Furthermore, NAC induced a marked decrease in splenomegaly with reduction
      in the frequency of the Jak2(V617F)-positive hematopoietic progenitors in BM and
      spleen. Altogether, overproduction of ROS is a mediator of JAK2(V617F)-induced
      DNA damages that promote disease progression. Targeting ROS accumulation might
      prevent the development of JAK2(V617F) MPNs.

PMID- 23558527
TI  - In-stem labelling allows visualization of DNA strand displacements by distinct
      fluorescent colour change.
AB  - The combination of thiazole orange (TO) and thiazole red (TR) as an internal pair
      of fluorescent DNA base surrogates ("DNA traffic lights") allows us to follow at
      least two consecutive DNA strand displacements in real time through a distinct
      fluorescence colour change from green to red and vice versa.

PMID- 23558528
TI  - Draft Genome Sequence of a Mannheimia haemolytica Serotype 6 Isolate Collected
      from the Nasopharynx of a Beef Calf with Bovine Respiratory Disease.
AB  - The draft genome of a Mannheimia haemolytica serotype 6 isolate obtained from the
      nasopharynx of a feedlot calf with bovine respiratory disease is described.

PMID- 23558529
TI  - Genome Sequence of the Basidiomycetous Yeast Pseudozyma antarctica T-34, a
      Producer of the Glycolipid Biosurfactants Mannosylerythritol Lipids.
AB  - The basidiomycetous yeast Pseudozyma antarctica T-34 is an excellent producer of
      mannosylerythritol lipids (MELs), members of the multifunctional extracellular
      glycolipids, from various feedstocks. Here, the genome sequence of P. antarctica
      T-34 was determined and annotated. Analysis of the sequence might provide
      insights into the properties of this yeast that make it superior for use in the
      production of functional glycolipids, leading to the further development of P.
      antarctica for industrial applications.

PMID- 23558530
TI  - Genome Sequencing of Bacillus subtilis Strain XF-1 with High Efficiency in the
      Suppression of Plasmodiophora brassicae.
AB  - The genome of the rhizobacterium Bacillus subtilis XF-1 is 4.06 Mb in size and
      harbors 3,853 coding sequences (CDS). Giant gene clusters were dedicated to the
      nonribosomal synthesis of antimicrobial lipopeptides and polyketides. Remarkably,
      XF-1 possesses a gene cluster involved in the synthesis of chitosanase that is
      related to the suppression of the pathogen Plasmodiophora brassicae.

PMID- 23558531
TI  - Complete Genome Sequence of Wohlfahrtiimonas chitiniclastica Strain SH04,
      Isolated from Chrysomya megacephala Collected from Pudong International Airport
      in China.
AB  - Wohlfahrtiimonas chitiniclastica bacilli that live in the larvae of a parasitic
      fly were recently isolated and are speculated to be the cause of fulminant
      sepsis. Here we report and analyze the complete genome sequence of
      Wohlfahrtiimonas chitiniclastica strain SH04. No complete genome sequence of a
      Wohlfahrtiimonas chitiniclastica isolate has been documented previously.

PMID- 23558532
TI  - Complete Genome Sequence of Serratia marcescens WW4.
AB  - Serratia marcescens WW4 is a biofilm-forming bacterium isolated from paper
      machine aggregates. Under conditions of phosphate limitation, this bacterium
      exhibits intergeneric inhibition of Pseudomonas aeruginosa. Here, the complete
      genome sequence of S. marcescens WW4, which consists of one circular chromosome
      (5,241,455 bp) and one plasmid (pSmWW4; 3,248 bp), was determined.

PMID- 23558533
TI  - Draft Genome Sequence of Acinetobacter baumannii Strain MSP4-16.
AB  - We report the 4.0-Mb draft genome sequence of Acinetobacter baumannii strain MSP4
      16, isolated from a mangrove soil sample from Parangipettai (11 degrees 30'N, 79
      degrees 47'E), Tamil Nadu, India. The draft genome sequence of strain MSP4-16
      consists of 3,944,542 bp, with a G+C content of 39%, 5,387 protein coding genes,
      and 69 RNAs.

PMID- 23558534
TI  - Draft Genome Sequence of Amycolatopsis decaplanina Strain DSM 44594T.
AB  - We report the 8.5-Mb genome sequence of Amycolatopsis decaplanina strain DSM
      44594(T), isolated from a soil sample from India. The draft genome of strain DSM
      44594(T) consists of 8,533,276 bp with a 68.6% G+C content, 7,899 protein-coding
      genes, and 57 RNAs.

PMID- 23558535
TI  - Draft Genome Sequence of Rhodococcus ruber Strain BKS 20-38.
AB  - We report the 6.1-Mb genome sequence of Rhodococcus ruber strain BKS 20-38,
      isolated from the palm tree rhizosphere soil of Bhitarkanika National Park,
      Odhisha, India. The draft genome sequence of strain BKS 20-38 consists of
      6,126,900 bp, with a G+C content of 69.72%, 5,716 protein-coding genes, and 49
      RNAs.

PMID- 23558536
TI  - Whole-Genome Shotgun Assembly and Analysis of the Genome of Streptomyces
      mobaraensis DSM 40847, a Strain for Industrial Production of Microbial
      Transglutaminase.
AB  - Here, we report the draft annotated genome sequence of Streptomyces mobaraensis
      strain DSM 40847, which is used in industry to produce microbial
      transglutaminase. The genome sequence will allow for the characterization of the
      molecular mechanisms underlying the beneficial properties of this organism.

PMID- 23558537
TI  - Draft Genome Sequence of the Rice Endophyte Burkholderia kururiensis M130.
AB  - Burkholderia kururiensis M130 is one of the few characterized rice endophytes and
      was isolated from surface-sterilized rice roots. This bacterium shows strong
      growth-promoting effects, being able to increase rice yields. Here we present its
      draft genome sequence, which contains important traits for endophytic life and
      plant growth promotion.

PMID- 23558539
TI  - Macrocyclic spermidine alkaloids from Androya decaryi L. Perrier.
AB  - Three new spermidine alkaloids and two known compounds were isolated from the
      leaves of Androya decaryi. Their structures were elucidated on the basis of their
      spectroscopic data (NMR and mass spectrometry), by X-Ray diffraction and by
      comparison with literature values. Evaluation of the in vitro antiplamosdial
      properties of the isolated compounds revealed they did not possess any
      significant activity.

PMID- 23558540
TI  - Design, synthesis, binding and docking-based 3D-QSAR studies of 2
      pyridylbenzimidazoles--a new family of high affinity CB1 cannabinoid ligands.
AB  - A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and
      synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used
      as a template for optimization. In the present series, 21 compounds displayed
      high affinities with Ki values in the nanomolar range. JM-39 (compound 39) was
      the most active of the series (KiCB1 = 0.53 nM), while compounds 31 and 44
      exhibited similar affinities to WIN 55212-2. CoMFA analysis was performed based
      on the biological data obtained and resulted in a statistically significant CoMFA
      model with high predictive value (q2 = 0.710, r2 = 0.998, r2pred = 0.823).

PMID- 23558541
TI  - Steroidal triterpenes of cholesterol synthesis.
AB  - Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that
      leads to cholesterol, an essential structural component of mammalian cell
      membranes, required for proper membrane permeability and fluidity. The last part
      of the pathway involves steroidal triterpenes with cholestane ring structures. It
      starts by conversion of acyclic squalene into lanosterol, the first sterol
      intermediate of the pathway, followed by production of 20 structurally very
      similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due
      to the structural similarities of sterol intermediates and the broad substrate
      specificity of the enzymes involved (especially sterol-Delta24-reductase; DHCR24)
      the exact sequence of the reactions between lanosterol and cholesterol remains
      undefined. This article reviews all hitherto known structures of post-squalene
      steroidal triterpenes of cholesterol synthesis, their biological roles and the
      enzymes responsible for their synthesis. Furthermore, it summarises kinetic
      parameters of enzymes (Vmax and Km) and sterol intermediate concentrations from
      various tissues. Due to the complexity of the post-squalene cholesterol synthesis
      pathway, future studies will require a comprehensive meta-analysis of the pathway
      to elucidate the exact reaction sequence in different tissues, physiological or
      disease conditions. A major reason for the standstill of detailed late
      cholesterol synthesis research was the lack of several steroidal triterpene
      standards. We aid to this efforts by summarizing commercial and laboratory
      standards, referring also to chemical syntheses of meiosis-activating sterols.

PMID- 23558542
TI  - Effect of a combination of low level ozone and metal ions on reducing Escherichia
      coli O157:H7 and Listeria monocytogenes.
AB  - Ozonated water has been used as a strong antimicrobial agent against foodborne
      pathogens. In this study, the combined effect of low level ozonated water and
      different added components, including 0.2% starch and metal ions (1 mM CuCl2.2H2O
      and 0.1 mM AgNO3), on inactivation of Escherichia coli O157:H7 and Listeria
      monocytogenes was investigated. Treatment with 0.4 ppm ozonated water for 30 min
      resulted in a maximum log reduction in E. coli O157:H7 and L. monocytogenes
      compared to initial bacterial counts. The log reductions of bacteria in a starch
      solution containing ozonated water were slightly higher than those in ozonated
      water alone. Furthermore, the log reductions of E. coli O157:H7 (2.59 and 4.71
      log cfu/mL) and L. monocytogenes (2.53 and 4.28 log cfu/mL) in a metal ion
      solution containing 0.2 and 0.4 ppm ozone for 30 min were significantly higher
      than those of the water and starch added groups (p < 0.05). These results
      indicate that a combination of ozonated water and metal ions may be useful as a
      antimicrobial agent.

PMID- 23558543
TI  - The third dimension of reading the sugar code by lectins: design of glycoclusters
      with cyclic scaffolds as tools with the aim to define correlations between
      spatial presentation and activity.
AB  - Coding of biological information is not confined to nucleic acids and proteins.
      Endowed with the highest level of structural versatility among biomolecules, the
      glycan chains of cellular glycoconjugates are well-suited to generate molecular
      messages/signals in a minimum of space. The sequence and shape of
      oligosaccharides as well as spatial aspects of multivalent presentation are
      assumed to underlie the natural specificity/selectivity that cellular glycans
      have for endogenous lectins. In order to eventually unravel structure-activity
      profiles cyclic scaffolds have been used as platforms to produce glycoclusters
      and afford valuable tools. Using adhesion/growth-regulatory galectins and the pan
      galectin ligand lactose as a model, emerging insights into the potential of
      cyclodextrins, cyclic peptides, calixarenes and glycophanes for this purpose are
      presented herein. The systematic testing of lectin panels with spatially defined
      ligand presentations can be considered as a biomimetic means to help clarify the
      mechanisms, which lead to the exquisite accuracy at which endogenous lectins
      select their physiological counterreceptors from the complexity of the cellular
      glycome.

PMID- 23558546
TI  - How visual short-term memory maintenance modulates subsequent visual
      aftereffects.
AB  - Prolonged viewing of a visual stimulus can result in sensory adaptation, giving
      rise to perceptual phenomena such as the tilt aftereffect (TAE). However, it is
      not known if short-term memory maintenance induces such effects. We examined how
      visual short-term memory (VSTM) maintenance modulates the strength of the TAE
      induced by subsequent visual adaptation. We reasoned that if VSTM maintenance
      induces aftereffects on subsequent encoding of visual information, then it should
      either enhance or reduce the TAE induced by a subsequent visual adapter,
      depending on the congruency of the memory cue and the adapter. Our results were
      consistent with this hypothesis and thus indicate that the effects of VSTM
      maintenance can outlast the maintenance period.

PMID- 23558545
TI  - The curse of planning: dissecting multiple reinforcement-learning systems by
      taxing the central executive.
AB  - A number of accounts of human and animal behavior posit the operation of parallel
      and competing valuation systems in the control of choice behavior. In these
      accounts, a flexible but computationally expensive model-based reinforcement
      learning system has been contrasted with a less flexible but more efficient model
      free reinforcement-learning system. The factors governing which system controls
      behavior-and under what circumstances-are still unclear. Following the hypothesis
      that model-based reinforcement learning requires cognitive resources, we
      demonstrated that having human decision makers perform a demanding secondary task
      engenders increased reliance on a model-free reinforcement-learning strategy.
      Further, we showed that, across trials, people negotiate the trade-off between
      the two systems dynamically as a function of concurrent executive-function
      demands, and people's choice latencies reflect the computational expenses of the
      strategy they employ. These results demonstrate that competition between multiple
      learning systems can be controlled on a trial-by-trial basis by modulating the
      availability of cognitive resources.

PMID- 23558547
TI  - Attentional capture does not depend on feature similarity, but on target
      nontarget relations.
AB  - What factors determine which stimuli of a scene will be visually selected and
      become available for conscious perception? The currently prevalent view is that
      attention operates on specific feature values, so attention will be drawn to
      stimuli that have features similar to those of the sought-after target. Here, we
      show that, instead, attentional capture depends on whether a distractor's feature
      relationships match the target-nontarget relations (e.g., redder). In three
      spatial-cuing experiments, we found that (a) a cue with the target color (e.g.,
      orange) can fail to capture attention when the cue-cue-context relations do not
      match the target-nontarget relations (e.g., redder target vs. yellower cue),
      whereas (b) a cue with the nontarget color can capture attention when its
      relations match the target-nontarget relations (e.g., both are redder). These
      results support a relational account in which attention is biased toward feature
      relationships instead of particular feature values, and show that attentional
      capture by an irrelevant distractor does not depend on feature similarity, but
      rather depends on whether the distractor matches or mismatches the target's
      relative attributes (e.g., relative color).

PMID- 23558548
TI  - Tool integration and dynamic touch.

PMID- 23558549
TI  - Easy to retrieve but hard to believe: metacognitive discounting of the
      unpleasantly possible.
AB  - People who recall or forecast many pleasant moments should perceive themselves as
      happier in the past or future than people who generate few such moments; the same
      principle should apply to generating unpleasant moments and perceiving
      unhappiness. Five studies suggest that this is not always true. Rather, people's
      metacognitive experience of ease of thought retrieval ("fluency") can affect
      perceived well-being over time beyond actual thought content. The easier it is to
      recall positive past experiences, the happier people think they were at the time;
      likewise, the easier it is to recall negative past experiences, the unhappier
      people think they were. But this is not the case for predicting the future.
      Although people who easily generate positive forecasts predict more future
      happiness, people who easily generate negative forecasts do not infer future
      unhappiness. Given pervasive tendencies to underestimate the likelihood of
      experiencing negative events, people apparently discount hard-to-believe
      metacognitive feelings (e.g., easily imagined unpleasant futures). Paradoxically,
      people's well-being may be maximized when they contemplate some bad moments or
      just a few good moments.

PMID- 23558550
TI  - Two signatures of implicit intergroup attitudes: developmental invariance and
      early enculturation.
AB  - Long traditions in the social sciences have emphasized the gradual
      internalization of intergroup attitudes and the putatively more basic tendency to
      prefer the groups to which one belongs. In four experiments (N = 883) spanning
      two cultures and two status groups within one of those cultures, we obtained new
      evidence that implicit intergroup attitudes emerge in young children in a form
      indistinguishable from adult attitudes. Strikingly, this invariance from
      childhood to adulthood holds for members of socially dominant majorities, who
      consistently favor their in-group, as well as for members of a disadvantaged
      minority, who, from the early moments of race-based categorization, do not show a
      preference for their in-group. Far from requiring a protracted period of
      internalization, implicit intergroup attitudes are characterized by early
      enculturation and developmental invariance.

PMID- 23558551
TI  - Riding other people's coattails: individuals with low self-control value self
      control in other people.
AB  - Two laboratory experiments and one dyadic study of ongoing relationships of
      romantic partners examined how temporary and chronic deficits in self-control
      affect individuals' evaluations of other people. We suggest that when individuals
      lack self-control resources, they value such resources in other people. Our
      results support this hypothesis: We found that individuals low (but not high) in
      self-control use information about other people's self-control abilities when
      judging them, evaluating other people with high self-control more positively than
      those with low self-control. In Study 1, participants whose self-control was
      depleted preferred people with higher self-control, whereas nondepleted
      participants did not show this preference. In Study 2, we conceptually replicated
      this effect while using a behavioral measure of trait self-control. In Study 3,
      individuals with low (but not high) self-control reported greater dependence on
      dating partners with high self-control than on those with low self-control. We
      theorize that individuals with low self-control may use interpersonal
      relationships to compensate for their lack of personal self-control resources.

PMID- 23558552
TI  - Attention is spontaneously biased toward regularities.
AB  - Knowledge about regularities in the environment can be used to facilitate
      perception, memory, and language acquisition. Given this usefulness, we
      hypothesized that statistically structured sources of information receive
      attentional priority over noisier sources, independent of their intrinsic
      salience or goal relevance. We report three experiments that support this
      hypothesis. Experiment 1 shows that regularities bias spatial attention: Visual
      search was facilitated at a location containing temporal regularities, even
      though these regularities did not predict target location, timing, or identity.
      Experiments 2 and 3 show that regularities bias feature attention: Attentional
      capture doubled in magnitude when singletons appeared, respectively, in a color
      or dimension with temporal regularities among task-irrelevant stimuli.
      Prioritization of the locations and features of regularities is not easily
      accounted for in the conventional dichotomy between stimulus-driven and goal
      directed attention. This prioritization may in turn promote further statistical
      learning, helping the mind to acquire knowledge about stable aspects of the
      environment.

PMID- 23558553
TI  - Coronary artery fistulas in children. Evaluation with 64-slice multidetector CT.
AB  - OBJECTIVES: There are various types of coronary artery fistulas (CAF) with
      complex shapes. Therefore, it is important to make a correct diagnosis and to
      understand the relationship of the CAF to the adjacent structures before
      transcatheter occlusion or surgery. This study evaluated the feasibility of using
      64-slice multidetector computed tomography (MDCT) angiography in diagnosing CAF.
      METHODS: Two readers who were blinded to the results of echocardiography,
      intervention, or surgery retrospectively evaluated the coronary MDCT appearances
      of CAF in 10 patients (4 boys and 6 girls; mean age, 2.9 years; range, 1-6
      years). The origin, course, and distal entry site of the fistula were determined.
      The diameters of the origin and the distal entry site were measured and compared
      with those seen during intervention or surgery. RESULTS: The origin, course, and
      distal vessel entry site of the CAF were clearly outlined in all patients by
      MDCT. The distal vessel draining site involved a single entry vessel in all
      patients. Seven fistulas involved the right coronary artery, and three involved
      the left coronary artery. Four fistulas drained into the right ventricle, four
      into the right atrium, and two into the left ventricle. The diagnosis of CAF
      using MDCT was in accordance with diagnoses made during intervention or surgery.
      There was an excellent correlation between MDCT and transcatheter occlusion in
      quantifying the diameters of the origin and distal entry site (R = 0.90 and 0.92,
      respectively, P < 0.05). CONCLUSION: Coronary 64-slice MDCT angiography depicted
      the whole shape and course of the CAF as well as of the surrounding structures.
      It may serve as a noninvasive diagnostic tool when planning a therapeutic
      strategy.

PMID- 23558554
TI  - Persistent left superior vena cava. Report of 3 patients undergoing device
      implantation.

PMID- 23558555
TI  - miRNA and TMPRSS2-ERG do not mind their own business in prostate cancer cells.
AB  - Oncogenic fusion proteins belong to an important class that disrupts gene
      expression networks in a cell. Astonishingly, fusion-positive prostate cancer
      cells enable the multi-gene regulatory capability of miRNAs to remodel the signal
      transduction landscape, enhancing or antagonizing the transmission of information
      to downstream effectors. Accumulating evidence substantiates the fact that miRNAs
      translate into dose-dependent responsiveness of cells to signaling regulators in
      transmembrane protease serine 2:ETS-related gene (TMPRSS2-ERG)-positive cells.
      Wide ranging signaling proteins are the targets for the degree of quantitative
      fluctuations imposed by miRNAs. miRNA signatures are aberrantly expressed in
      fusion-positive cancer cells, suggesting that they have a cumulative effect on
      tumor aggressiveness. It seems attractive to note that TMPRSS2:ERG fusion has a
      stronger effect as tumors positive for the oncogenic TMPRSS2:ERG have
      dysregulated oncomirs and tumor suppressor miRNA signature. It is undeniable that
      a comprehensive analysis of the prostate cancer microRNAome is necessary to
      uncover novel microRNAs and pathways associated with prostate cancer. Moreover,
      the identification and validation of miRNA signature in TMPRSS2-ERG-positive
      prostate cancer cells may help to identify novel molecular targets and pathways
      for personalized therapy.

PMID- 23558556
TI  - IgH loci of American alligator and saltwater crocodile shed light on IgA
      evolution.
AB  - Immunoglobulin loci of two representatives of the order Crocodylia were studied
      from full genome sequences. Both Alligator mississippiensis and Crocodylus
      porosus have 13 genes for the heavy chain constant regions of immunoglobulins.
      The IGHC locus contains genes encoding four immunoglobulins M (IgM), one
      immunoglobulin D (IgD), three immunoglobulins A (IgA), three immunoglobulins Y
      (IgY), and two immunoglobulins D2 (IgD2). IgA and IgD2 genes were found in
      reverse transcriptional orientation compared to the other Ig genes. The IGHD gene
      contains 11 exons, four of which containing stop codons or sequence alterations.
      As described in other reptiles, the IgD2 is a chimeric Ig with IgA- and IgD
      related domains. This work clarifies the origin of bird IgA and its evolutionary
      relationship with amphibian immunoglobulin X (IgX) as well as their links with
      mammalian IgA.

PMID- 23558558
TI  - Cloning of a hamster anti-mouse CD79B antibody sequences and identification of a
      new hamster immunoglobulin lambda constant IGLC gene region.
AB  - Anti-CD79 antibodies have been effective at targeting B cell lymphoma cells and
      depleting B cells in animal models. In order to engineer recombinant antibodies
      with additional effector functions in mice, we cloned and sequenced the full
      length cDNAs of the heavy and light chain of a hamster anti-mouse CD79B antibody.
      Although hamster antibodies represent a unique source of monoclonal antibodies
      against mouse, rat, and human antigens, sequence information of hamster
      immunoglobulins (IG) is sparse. Here, we report a new hamster (Cricetulus
      migratorius) IG lambda constant (IGLC) gene region that is most homologous to
      mouse IGLC2 and IGLC3.

PMID- 23558560
TI  - Synthesis of highly piezoelectric lead-free (K, Na)NbO3 one-dimensional
      perovskite nanostructures.
AB  - High-aspect-ratio single-crystalline KNN nanorods (length ~10-20 MUm and diameter
      ~400 nm) are synthesized using a facile method based on a molten-salt reaction,
      whose formation mechanism has been revealed. The lead-free piezoelectric nanorods
      showing high piezoelectric coefficient d*33 up to ~230 pm V(-1) may be used in
      bio-sensing and energy-harvesting micro-devices.

PMID- 23558559
TI  - Feasibility and pharmacokinetics of combined therapy with S-1 and trastuzumab in
      patients with human epidermal growth factor receptor 2-positive metastatic or
      recurrent breast cancer.
AB  - BACKGROUND: To clarify the tolerance and pharmacokinetics of combined therapy
      with S-1 and trastuzumab in patients with human epidermal growth factor receptor
      2 (HER2)-positive metastatic or recurrent breast cancer. METHODS: From January
      2008 through to September 2009, combined therapy with S-1 and trastuzumab was
      given to 7 patients with HER2-positive metastatic or recurrent breast cancer. The
      incidence of adverse events and the pharmacokinetics of tegafur, 5-fluorouracil,
      and gimeracil in plasma were studied. RESULTS: One patient had grade 3
      leukopenia, and another had a grade 3 elevation of alanine aminotransferase. All
      other adverse events were grade 2 or lower. The combination of S-1 and
      trastuzumab did not cause any new adverse events. The incidence of adverse events
      was similar to those associated with S-1 alone. The median number of treatment
      cycles was 11. The pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil
      after treatment with S-1 plus trastuzumab did not markedly differ from those
      after S-1 alone. CONCLUSIONS: Combined therapy with S-1 and trastuzumab did not
      cause any new adverse events, administration continuity was good, and the therapy
      was well tolerated.

PMID- 23558557
TI  - Comprehensive survey and genomic characterization of Toll-like receptors (TLRs)
      in channel catfish, Ictalurus punctatus: identification of novel fish TLRs.
AB  - A comprehensive survey of channel catfish Toll-like receptors (TLRs) was
      undertaken following a genomic PCR approach based on degenerate primers. Twenty
      different TLRs were identified in channel catfish. Channel catfish TLR sequences
      were characterized by phylogenetic analysis based on their conserved
      Toll/interleukin-1 receptor domain and by in-depth analysis of leucine-rich
      repeat (LRR) motifs of the ligand binding extracellular domain (ECD). The catfish
      have representatives of all the TLR types defined in vertebrates with the
      exception of TLR6, TLR10, TLR11, TLR12, TLR13, TLR15, TLR23, and TLR24.
      Additionally, two new types were discovered: TLR25 and TLR26. TLR25 is also
      present in cyprinids, cichlids, plecoglossids, and adrianichthyids, suggesting
      its presence early in fish evolution. To date, TLR26 was found only in channel
      catfish. Like TLR18-23, TLR25 and TLR26 were not found in any other vertebrate
      classes and appear to be fish specific. Data mining using the catfish TLR
      sequences revealed that in addition to ictalurids and cyprinids, TLR4 is also
      present in salmonids. TLR19 and TLR20 were both found in ictalurids, cyprinids,
      and salmonids, demonstrating a wider range than previously known. The LRR
      structure within ECDs appeared generally well conserved. TLR7 demonstrated a very
      high identity to human TLR7 strongly suggesting that ligand specificity maybe
      conserved. Finally, expression profiling confirmed that most TLRs are widely
      expressed in a diversity of tissues and revealed marked differences of expression
      level.

PMID- 23558561
TI  - Kinetic analysis of human and canine P-glycoprotein-mediated drug transport in
      MDR1-MDCK cell model: approaches to reduce false-negative substrate
      classification.
AB  - Madin-Darby canine kidney (MDCK) cells transfected with the multidrug resistance
      1 (MDR1) gene, MDR1-MDCK, are widely used as an in vitro model to classify
      compounds as human P-glycoprotein (hPgp) substrates or nonsubstrates. Because
      MDCK cells express endogenous canine Pgp (cPgp), which is prone to downregulation
      after transfection with hPgp, this situation could lead to false-negative
      classification of hPgp substrates. The aim of this study was to investigate
      factors that influence hPgp substrate classification in MDR1-MDCK model and to
      seek ways to reduce false classification. Three-compartment models were used to
      derive flux equations describing the drug transport processes; factors
      influencing hPgp substrate classification were evaluated by simulations. Pgp
      functionality was assessed by determining the bidirectional permeability of a
      series of test compounds. Expressions of hPgp and cPgp were measured by
      quantitative polymerase chain reaction (qPCR). Kinetic model analysis revealed
      that the current net flux ratio calculation for hPgp substrate classification is
      influenced by endogenous cPgp expression as well as hPgp-cPgp expression ratio;
      the effect was more pronounced in low hPgp-cPgp region and diminished in high
      ratio region. On the basis of kinetic considerations, this study provides a
      rational experimental approach and appropriate mathematical corrections to
      minimize the potential occurrence of false-negative classification of new
      molecular entities.

PMID- 23558562
TI  - Mixed lymphocyte reaction blocking factors (MLR-Bf) as potential biomarker for
      indication and efficacy of paternal lymphocyte immunization in recurrent
      spontaneous abortion.
AB  - OBJECTIVES: The majority of cases of unexplained recurrent spontaneous abortion
      (RSA) remains unclear and is found to be associated with alloimmune antibodies
      termed as mixed lymphocyte reaction blocking factor (MLR-Bf). The decreased
      production of MLR-Bf may play major role in the immunologic failure of pregnancy
      and can lead to abortion. The present study was aimed at evaluating MLR-Bf as
      potential biomarker of indication and the efficacy of immunotherapy with paternal
      lymphocytes (LIT) in women with RSA. MATERIALS AND METHODS: A total of 97 women
      with history of unexplained RSA were recruited for this prospective study. These
      women showed negative for MLR-Bf and registered for lymphocyte immunotherapy with
      husband cells. Women with autoimmune pathology or anti-phospholipid syndrome were
      excluded. All individuals gave their consent to participate in the study.
      RESULTS: We have analyzed MLR proliferative response and MLR-Bf in nonpregnant
      women with history of RSA before and after LIT. Following LIT, the initially low
      MLR proliferative response was restored at 76.6 % of women, and MLR-Bf activity
      in blood serum could be detected in 74 % of women. The rate of successful
      pregnancy was shown to be significantly higher in women positive for MLR-Bf
      (50/72) as compared with the MLR-Bf negative women (7/25; chi (2) = 0.0003).
      CONCLUSION: The data obtained demonstrate that LIT with the paternal lymphocytes
      in MLR-Bf negative women is accompanied by increased proliferative cell response
      to the paternal alloantigens and by enhanced production of soluble suppressor
      activity factors (MLR-Bf) that is associated with improved pregnancy outcome in
      women with history of RSA.

PMID- 23558563
TI  - Iron overload causes oxidative stress and impaired insulin signaling in AML-12
      hepatocytes.
AB  - BACKGROUND: Iron overload is associated with increased severity of nonalcoholic
      fatty liver disease (NAFLD) including progression to nonalcoholic steatohepatitis
      and hepatocellular carcinoma. AIMS: To identify potential role(s) of iron in
      NAFLD, we measured its effects on pathways of oxidative stress and insulin
      signaling in AML-12 mouse hepatocytes. METHODS: Rapid iron overload was induced
      with 50 MUM ferric ammonium citrate and 8-hydroxyquinoline. Insulin response was
      measured by Western blot of phospho-protein kinase B. Lipid content was
      determined by staining with Oil Red O. Reactive oxygen species (ROS) were
      measured by flow cytometry using 5-(and 6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate. Oxidative stress was measured by Western
      blots for phospho-jnk and phospho-p38. RESULTS: Iron increased ROS (p < 0.001)
      and oxidative stress (p < 0.001) and decreased insulin signaling by 33 % (p <
      0.001). Treatment with stearic or oleic acids (200 MUM) increased cellular lipid
      content and differentially modulated effects of iron. Stearic acid potentiated
      iron-induced ROS levels by two-fold (p < 0.05) and further decreased insulin
      response 59 % (p < 0.05) versus iron alone. In contrast, cells treated with oleic
      acid were protected against iron-mediated injury; ROS levels were decreased by
      half (p < 0.01) versus iron alone while insulin response was restored to control
      (untreated) levels. The anti-oxidant curcumin reduced effects of iron on insulin
      signaling, ROS, and oxidative stress (p < 0.01). Curcumin was similarly effective
      in cells treated with both stearic acid and iron. CONCLUSIONS: An in vitro model
      of NAFLD progression is described in which iron-induced oxidative stress inhibits
      insulin signaling. Pathophysiological effects of iron were increased by saturated
      fat and decreased by curcumin.

PMID- 23558565
TI  - Design, synthesis, biological evaluation, and molecular docking studies of
      quinolone derivatives as potential antitumor topoisomerase I inhibitors.
AB  - A novel series of quinolone derivatives (6a-n) were designed and synthesized, and
      their biological activities were evaluated as potential antitumor topoisomerase I
      (Top I) inhibitors. Among these compounds, 6j exhibited the most potent antitumor
      activities against multiple cancer cell lines. Docking simulation was performed
      to insert compound 6j into the crystal structure of DNA-Top I to determine the
      probable binding model.

PMID- 23558564
TI  - Ultra-performance liquid chromatography tandem mass spectrometry method for the
      determination of AZ66, a sigma receptor ligand, in rat plasma and its application
      to in vivo pharmacokinetics.
AB  - Methamphetamine abuse continues as a major problem in the USA owing to its
      powerful psychological addictive properties. AZ66, 3-[4-(4-cyclohexylpiperazine-1
      yl)pentyl]-6-fluorobenzo[d]thiazole-2(3H)-one, an optimized sigma receptor
      ligand, is a promising therapeutic agent against methamphetamine. To study the in
      vivo pharmacokinetics of this novel sigma receptor ligand in rats, a sensitive
      ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS)
      method was developed in rat plasma and validated. The developed method requires a
      small volume of plasma (100 MUL) and a simple liquid-liquid extraction. The
      chromatographic separations were achieved in 3.3 min using an Acquity UPLC BEH
      Shield RP18 column. The mass spectrophotometric detection was carried out using a
      Waters Micromass Quattro MicroTM triple-quadrupole system. Multiple reaction
      monitoring was used for the quantitation with transitions m/z 406 -> m/z 181 for
      AZ66 and m/z 448 -> m/z 285 for aripiprazole. The method was validated over a
      concentration range of 1-3500 ng/mL and the lower limit of quantitation was
      determined to be 1 ng/mL. Validation of the assay demonstrated that the developed
      UPLC/MS/MS method was sensitive, accurate and selective for the determination of
      AZ66 in rat plasma. The present method has been successfully applied to an i.v.
      pharmacokinetic study in Sprague-Dawley rats.

PMID- 23558566
TI  - Thermal evaporation-induced anhydrous synthesis of Fe3O4-graphene composite with
      enhanced rate performance and cyclic stability for lithium ion batteries.
AB  - We present a high-yield and low cost thermal evaporation-induced anhydrous
      strategy to prepare hybrid materials of Fe3O4 nanoparticles and graphene as an
      advanced anode for high-performance lithium ion batteries. The ~10-20 nm Fe3O4
      nanoparticles are densely anchored on conducting graphene sheets and act as
      spacers to keep the adjacent sheets separated. The Fe3O4-graphene composite
      displays a superior battery performance with high retained capacity of 868 mA h
      g(-1) up to 100 cycles at a current density of 200 mA g(-1), and 539 mA h g(-1)
      up to 200 cycles when cycling at 1000 mA g(-1), high Coulombic efficiency (above
      99% after 200 cycles), good rate capability, and excellent cyclic stability. The
      simple approach offers a promising route to prepare anode materials for practical
      fabrication of lithium ion batteries.

PMID- 23558567
TI  - K5/K14-positive cells contribute to salivary gland-like breast tumors with
      myoepithelial differentiation.
AB  - Salivary gland-like tumors of the breast show a great variety of architectural
      patterns and cellular differentiations such as glandular, myoepithelial,
      squamous, and even mesenchymal phenotypes. However, currently little is known
      about the evolution and cellular differentiation of these tumors. For that
      reason, we performed an in situ triple immunofluorescence lineage/differentiation
      tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and
      epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA;
      myoepithelial marker) with the aim to construct and trace different cell lineages
      and define their cellular hierarchy in tumors with myoepithelial differentiation.
      isTILT analysis of a series of 28 breast, salivary, and lacrimal gland tumors,
      including pleomorphic adenomas (n=8), epithelial-myoepithelial tumors (n=9), and
      adenoid cystic carcinomas (n=11) revealed that all tumor types contained K5/K14
      positive progenitor cells in varying frequencies from a few percent up to 15%.
      These K5/K14-positive tumor cells were found to differentiate to glandular-
      (K8/18-positive) and myoepithelial-lineage (SMA-positive)-specific cells and were
      also shown to generate various heterologeous cell differentiations such as
      squamous and mesenchymal progenies. p63 was co-expressed with K5/K14 in basal
      like progenitor cells, myoepithelial, and squamous cells but not in glandular
      cells. Our results show that the corresponding counterpart tumors of breast and
      salivary/lacrimal glands have identical cellular compositions. Taken together,
      our isTILT and RNA-expression data indicate that look-alike tumors of the breast
      represent a special subgroup of basal-type tumors with benign or usually low
      malignant potential.

PMID- 23558568
TI  - Cancerous 'floater': a lesson learned about tissue identity testing, endometrial
      cancer and microsatellite instability.
AB  - A 46-year-old woman presented with endometrial cells on a pap smear and underwent
      endometrial curettage. The specimen revealed secretory endometrium and a possible
      endometrial polyp. In addition, a single 4 mm fragment of well-differentiated
      adenocarcinoma was found. Tissue identity DNA genotyping was performed and the
      adenocarcinoma tissue fragment showed a drastically different allelic pattern
      from that of the background endometrium. To confirm tissue contamination,
      genotyping of three other tumor specimens-probable sources for a contaminant-was
      performed but failed to identify a match. Without confirmation of contamination,
      a second endometrial curettage was obtained from the patient, in which similar
      adenocarcinoma tissue was once again found. Further workup demonstrated that the
      patient had a microsatellite unstable (MSI) endometrial adenocarcinoma by
      immunohistochemistry and molecular testing. The patient subsequently underwent
      staging surgery, which revealed an early-stage, well-differentiated endometrioid
      adenocarcinoma. This case study illustrates an uncommon, yet important caveat of
      tissue identity testing by DNA genotyping, where MSI instability can
      significantly alter the allelic pattern of DNA polymorphisms in the tumor genome,
      leading to erroneous conclusion regarding the tissue identity. Awareness of this
      phenomenon is crucial for a molecular pathologist to avoid interpretation errors
      of tissue identity testing in a cancer diagnostic workup.

PMID- 23558569
TI  - The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade
      serous carcinoma from low-grade serous ovarian tumors.
AB  - Low-grade serous carcinomas and serous borderline tumors, combined herein and
      referred to as low-grade serous tumors, show distinct molecular alterations and
      clinical behaviors compared with high-grade serous carcinomas. The discrimination
      between low-grade serous tumors and high-grade serous carcinomas can be
      challenging on small tissue samples, such as cell blocks of paracentesis fluid or
      biopsies from omental disease. The purpose of this study was to test the ability
      of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous
      carcinomas and low-grade serous tumors on small tissue samples. Tissue
      microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous
      carcinomas, and 49 serous borderline tumors, confirmed by contemporary
      histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody
      clones, respectively). TP53 was scored as completely absent, wild-type pattern or
      overexpressed (>60%), and CDKN2A was scored as either negative/patchy (<90%) or
      block expression (>90%). The combination of the two markers, ie, the TP53 wild
      type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous
      tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a
      negative predictive value of 98%. These markers can, therefore, be used on small
      biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These
      findings may inform emerging neoadjuvant therapeutic strategies in advanced
      ovarian cancers and may be crucial for future clinical trials on molecular-based
      therapies.

PMID- 23558570
TI  - Expression of angiopoietin-TIE system components in angiosarcoma.
AB  - Angiosarcoma is an aggressive malignancy of endothelial differentiation.
      Potential roles of the endothelial angiopoietin-tunica interna endothelial cell
      kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and
      treatment are undefined. To examine the expression and prognostic significance of
      angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we
      immunohistochemically evaluated clinically annotated human angiosarcoma samples.
      Correlations of protein expression with overall survival and pathological
      features were explored. The cohort included 51 patients diagnosed with
      angiosarcoma at the age of 30-86 years (median 67). The 5-year overall survival
      was 45% with a median of 26 months. Moderate to strong expression of angiopoietin
      1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and
      moderate to strong expression of angiopoietin-2 was observed in 42% of
      angiosarcomas. Increased angiopoietin-1 expression correlated with improved
      survival. Non-significant trends toward longer survival were also observed with
      increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2,
      TIE1 and TEK (TIE2) was associated with vasoformative architecture. No
      differences in expression of these proteins were observed when patients were
      segregated by age, gender, presence or absence of metastases at diagnosis,
      primary tumor location, radiation association or the presence of necrosis. We
      conclude that components of the ANGPT-TIE system are commonly expressed in
      angiosarcomas. Reduced expression of these proteins is associated with non
      vasoformative and clinically more aggressive lesions.

PMID- 23558571
TI  - MET and MST1R as prognostic factors for classical Hodgkin's lymphoma.
AB  - MST1R (RON) and MET are receptor tyrosine kinase gene family members that form a
      noncovalent complex on the cell surface, a critical step in tumor progression. A
      recent study suggested a prognostic role of MET expression in Hodgkin/Reed
      Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL). The purpose of this
      study was to examine the prognostic significance of MET and MST1R expression in
      cHL. The prognostic impact of MET and MST1R was examined in 100 patients with cHL
      (median age: 32 years) by immunohistochemistry and mRNA in situ hybridization.
      The median follow-up time was 95 months (interquartile range: 42-126 months). MET
      or MST1R protein expression was associated with high MET or MST1R mRNA
      expression, respectively. Thirty-eight patients (38%) expressed MET protein in
      HRS cell, which was associated with better overall survival (P=0.004). Twenty-six
      patients (26%) expressed MST1R protein, which was associated with better overall
      survival (P=0.022) and event-free survival (P=0.021). Multivariate analysis
      identified MET protein as an independent prognostic factor for overall survival
      and MST1R protein as an independent prognostic factor for event-free survival.
      Subgroup analysis according to Ann Arbor stage showed that expressions of MET and
      MST1R protein have prognostic impact in the advanced stage only. In particular,
      coexpression of MST1R and MET protein was associated with a better survival
      outcome than MET or MST1R expression alone or no expression. This study suggests
      that MET and MST1R are independent prognostic factors in classical cHL, and may
      allow the identification of a subgroup of cHL patients who require more intensive
      therapy.

PMID- 23558572
TI  - Intrinsic breast cancer subtypes defined by estrogen receptor signalling
      prognostic relevance of progesterone receptor loss.
AB  - The majority of luminal type breast carcinomas are slowly growing tumors with an
      overall favorable prognosis. However, a proportion of cases (luminal B tumors)
      are characterized by coactivation of growth factor receptors or non-canonical ER
      signaling and a poorer clinical outcome. The aim of our study was to evaluate
      whether the expression of proteins that are part of the ER signaling network may
      be used to distinguish low-risk from high-risk luminal tumors. Unsupervised
      hierarchical clustering of a set of proteins either involved in estrogen receptor
      signaling or associated with resistance to endocrine therapy was performed in a
      series of 443 postmenopausal breast carcinomas. Using this approach, we were able
      to reproduce the established classification with two distinct groups of luminal
      (estrogen receptor positive) tumors, one group of HER2-associated tumors and a
      group of triple-negative tumors. However, neither proliferation nor the
      expression of one or more of the ER-co-factors or resistance-associated factors,
      but PR-expression was identified as the most important stratifier distinguishing
      between the two luminal groups. In fact, not only the four identified clusters
      were shown to be significantly associated with patient outcome, PR-expression
      alone or in combination with Ki-67-stains stratified ER-positive tumors into a
      low-risk and a high-risk group. Our data indicate that defining luminal B tumors
      by the presence of high-risk criteria (loss of PR-expression or increased
      proliferation) provides a robust and highly significant stratification of ER
      positive breast carcinomas into luminal A and B.

PMID- 23558573
TI  - SOX10 is a novel marker of acinus and intercalated duct differentiation in
      salivary gland tumors: a clue to the histogenesis for tumor diagnosis.
AB  - Salivary gland tumors are relatively rare and morphologically diverse and
      heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely
      needed to aid in diagnosing and determining the cell type of origin. SRY-related
      HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the
      specification of the neural crest and maintenance of Schwann cells and
      melanocytes. In addition, positive expression has also been implicated in the
      major salivary gland. Here, we examined SOX10 expression in various salivary
      gland tumors to correlate this expression with myoepithelial markers. Overall, 76
      malignant and 14 benign tumors were examined. SOX10 expression clearly delineated
      two distinct subtypes of human salivary gland tumors; acinic cell carcinomas,
      adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial
      carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component
      of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid
      carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10
      negative. Also, SOX10 was expressed in solid-type or non-specific morphology
      salivary gland tumors, but was not expressed in poorly differentiated squamous
      cell carcinomas. In normal human salivary gland tissue, SOX10 expression was
      specific to the nuclei of acini and both luminal and abluminal cells of
      intercalated ducts but not in other sites. Moreover, the murine model suggested
      that SOX10 continued to be expressed from the developmental stage to adulthood in
      the acinar and both luminal and abluminal intercalated ducts in the major
      salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding
      the histogenesis of salivary gland tumors.

PMID- 23558574
TI  - Immunodetection of phosphohistone H3 as a surrogate of mitotic figure count and
      clinical outcome in cutaneous melanoma.
AB  - In the American Joint Committee on Cancer (AJCC)-TNM (2009) staging system, the
      key prognostic factor in cutaneous melanoma is the depth of dermal invasion
      (Breslow thickness) with further refinement according to the presence of
      epidermal ulceration or dermal mitoses. Immunodetection of phosphohistone H3 has
      been shown to facilitate the identification of mitotic figures in various
      neoplasms. We selected 120 cases of primary cutaneous melanoma with completely
      annotated histopathologic parameters and clinical outcomes and performed double
      immunohistochemical staining for MLANA (Mart-1/Melan-A) and phosphohistone H3.
      One hundred and thirteen cases were amenable to antiphosphohistone H3 staining
      from 66 men and 47 women, with mean age of 64 years (9-93), including 61
      superficial spreading type, 24 nodular, 6 lentigo maligna, 8 acral lentiginous,
      and 14 unclassified. The mean Breslow thickness was 2.53 mm (0.20-25), ulceration
      was present in 25/113 (22%) and the mean mitotic count was 3.2/mm(2) (<1
      29/mm(2)). In 27/113 (24%) of the cases, antiphosphohistone H3 failed to
      highlight mitotic figures anywhere in the tissue (normal or tumor cell), whereas
      in 86/113 (76%) antiphosphohistone H3 detected at least one mitotic figure. Among
      the latter, antiphosphohistone H3 did not detect mitotic figures in dermal tumor
      cells in 37/86 cases (43%), whereas anti-PHH3 identified at least one melanocytic
      mitotic figure in the other 49/86 cases (57%; range: 1-66/mm(2)). The
      relationship between phosphohistone H3 and manual mitotic count was statistically
      significant (Pearson correlation=0.59, P<0.0001). Logistic regression analyses
      demonstrated an association between the development of subsequent metastatic
      disease and the following variables: mitotic figures (odds ratio (OR)=5.7;
      P=0.0001); phosphohistone H3-positive mitotic figures (OR=3.0; P=0.008); Breslow
      thickness (OR=4.0 per mm; P=0.0002); ulceration (OR=3.94; P=0.008). The
      application of phosphohistone H3 immunohistochemistry to the description of
      primary cutaneous melanoma is useful in identifying mitotic figures, improves
      upon the specificity of this designation when used together with MLANA, and
      correlates with an increased risk for metastasis in univariate analyses.

PMID- 23558575
TI  - The pathology of magnetic-resonance-imaging-negative epilepsy.
AB  - Patients with magnetic-resonance-imaging (MRI)-negative (or 'nonlesional')
      pharmacoresistant focal epilepsy are the most challenging group undergoing
      presurgical evaluation. Few large-scale studies have systematically reviewed the
      pathological substrates underlying MRI-negative epilepsies. In the current study,
      histopathological specimens were retrospectively reviewed from MRI-negative
      epilepsy patients (n=95, mean age=30 years, 50% female subjects). Focal cortical
      dysplasia cases were classified according to the International League Against
      Epilepsy (ILAE) and Palmini et al classifications. The most common pathologies
      found in this MRI-negative cohort included: focal cortical dysplasia (n=43, 45%),
      gliosis (n=21, 22%), hamartia+gliosis (n=12, 13%), and hippocampal sclerosis
      (n=9, 9%). The majority of focal cortical dysplasia were ILAE type I (n=37) or
      Palmini type I (n=39). Seven patients had no identifiable pathological
      abnormalities. The existence of positive pathology was not significantly
      associated with age or temporal/extratemporal resection. Follow-up data post
      surgery was available in 90 patients; 63 (70%) and 57 (63%) attained seizure
      freedom at 6 and 12 months, respectively. The finding of positive pathology was
      significantly associated with seizure-free outcome at 6 months (P=0.035), but not
      at 12 months. In subgroup analysis, the focal cortical dysplasia group was not
      significantly correlated with seizure-free outcome, as compared with the negative
      pathology groups at either 6 or 12 months. Of note, the finding of hippocampal
      sclerosis had a significant positive correlation with seizure-free outcome when
      compared with the negative-pathology group (P=0.009 and 0.004 for 6- and 12-month
      outcome, respectively). Absence of a significant histopathology in the resected
      surgical specimen did not preclude seizure freedom. In conclusion, our study
      highlights the heterogeneity of epileptic pathologies in MRI-negative epilepsies,
      with focal cortical dysplasia being the most common finding. The existence of
      positive pathology in surgical specimen may be a good indication for short-term
      good seizure outcome. There is a small subset of cases in which no pathological
      abnormalities are identified.

PMID- 23558576
TI  - Immunohistochemical stains for CD3 and CD8 do not improve detection of gluten
      sensitive enteropathy in duodenal biopsies.
AB  - Patients with gluten-sensitive enteropathy usually have increased numbers of
      duodenal intraepithelial lymphocytes even if the villous architecture is normal.
      Some authors advocate the use of CD8 and CD3 immunohistochemical stains to
      improve detection of intraepithelial lymphocytosis, yet the added value of
      immunohistochemistry when biopsies appear normal remains unproven. The purpose of
      this study was to evaluate the utility of CD3 and CD8 immunostains in detecting
      intraepithelial lymphocytosis among duodenal biopsies originally interpreted to
      be normal based on routine evaluation. We identified 200 duodenal biopsies from
      172 patients, all of which were accompanied by a clinical question of gluten
      sensitive enteropathy. Five well-oriented villi from each biopsy were assessed.
      Intraepithelial lymphocytes present in hematoxylin and eosin (H&E)-stained slides
      were counted and compared with the number of CD3 and CD8 immunopositive cells
      present in the villous epithelium. Results were expressed as the mean number of
      intraepithelial lymphocytes or immunopositive cells present per 20 villous tip
      enterocytes. Review of H&E-stained slides revealed a mean of 2.1 +/- 0.1
      intraepithelial lymphocytes, compared with 3.2 +/- 0.1 CD3-positive and 2.1 +/-
      0.1 CD8-positive intraepithelial cells (P=<0.001 and 1, respectively), although
      none of the cases displayed sufficient numbers of intraepithelial lymphocytes to
      be considered abnormal (ie, >= 12/20 enterocytes) by any method. The number of
      intraepithelial lymphocytes detected by H&E evaluation or immunohistochemistry
      did not correlate with results of serologic studies for markers of gluten
      sensitivity. We conclude that immunostains for T cell markers do not improve
      detection of gluten-sensitive enteropathy when H&E-stained sections are normal.

PMID- 23558577
TI  - Neutrophilic bacterial meningitis: pathology and etiologic diagnosis of fatal
      cases.
AB  - The frequency of fatalities due to acute bacterial meningitis has decreased
      significantly due to vaccinations, early diagnoses, and treatments. We studied
      brain tissues of patients with fatal neutrophilic meningitis referred to the
      Centers for Disease Control for etiologic diagnosis from 2000-2009 to highlight
      aspects of the disease that may be preventable or treatable. Demographic,
      clinical, and laboratory data were extracted from records. Of 117 cases in the
      database with a diagnosis of meningitis or meningoencephalitis, 39 had
      neutrophilic inflammation in the meninges. Inflammatory cells infiltrated the
      superficial cortex in 16 of 39 (41%) cases. Bacteria were found using Gram and
      bacterial silver stains in 72% of cases, immunohistochemistry in 69% (including
      two cases where the meningococcus was found outside the meninges), and PCR in
      74%. Streptococcus pneumoniae was the cause of the meningitis in 14 patients and
      Neisseria meningitidis in 9. In addition, Streptococcus spp. were found to be the
      cause in six cases, while Staphylococcus aureus, Staphylococcus spp.,
      Enterococcus spp., and Fusobacterium were the cause of one case each. There were
      six cases in which no specific etiological agent could be determined. The mean
      age of the patients with S. pneumoniae was 39 years (range 0-65), with N.
      meningitidis was 19 years (range 7-51), whereas that for all others was 31 years
      (range 0-68). In summary, our study shows that S. pneumoniae continues to be the
      most frequent cause of fatal neutrophilic bacterial meningitis followed by N.
      meningitidis, both vaccine preventable diseases.

PMID- 23558578
TI  - The liver in itai-itai disease (chronic cadmium poisoning): pathological features
      and metallothionein expression.
AB  - Cadmium (Cd) is a highly hepatotoxic heavy metal, which is widely dispersed in
      the environment. Acute Cd hepatotoxicity has been well studied in experimental
      animals; however, effects of prolonged exposure to Cd doses on the liver remain
      unclear. In the present study, to evaluate chronic Cd hepatotoxicity, we examined
      specimens from cases of itai-itai disease, the most severe form of chronic Cd
      poisoning. We compared 89 cases of itai-itai disease with 27 control cases to
      assess Cd concentration in organs. We also examined 80 cases of itai-itai disease
      and 70 control cases for histopathological evaluation. In addition, we performed
      immunohistochemistry for metallothionein, which binds and detoxifies Cd. Hepatic
      Cd concentration was higher than Cd concentration in all other organs measured in
      the itai-itai disease group, whereas it was second highest following renal
      concentration in the control group. In the liver in the itai-itai disease group,
      fibrosis was observed at a significantly higher rate than that in the control
      group. Metallothionein expression was significantly higher in the itai-itai
      disease group than that in the control group. Prolonged exposure to low doses of
      Cd leads to high hepatic accumulation, which can then cause fibrosis; however, it
      also causes high expression of metallothionein, which is thought to reduce Cd
      hepatotoxicity.

PMID- 23558579
TI  - Non-fusion and growing instrumentation in the correction of congenital spinal
      deformity associated with split spinal cord malformation: an early follow-up
      outcome.
AB  - STUDY DESIGN: A retrospective case review. INTRODUCTION: To evaluate the safety
      and efficacy of the non-fusion technique in achieving and maintaining the proper
      correction for congenital spinal deformity (CSD) and allowing normal spinal
      growth in patients with split spinal cord malformation (SSCM). MATERIALS AND
      METHODS: Seven patients who had CSD and SSCM were adopted, with a mean age of 8
      years. All the patients in this study received Halo-gravity traction (HGT) prior
      to expansion of the spine and instrumentation with vertical expandable titanium
      prosthetic rib, growing rod or their hybrid. Five of them underwent opening wedge
      thoracoplasty simultaneously. And the two patients with type I SSCM underwent
      bony spur excision in the initial surgery before corrective manipulation. Then
      all the patients received a lengthened operation every six months. Changes of
      their major curve and length of T1-S1 spine were measured, and complications,
      neurological status were recorded. All the patients were followed up with an
      average of 32.6 months. RESULTS: Their mean major curve improved from 90.1
      degrees  to 58.6 degrees  with a correction rate of 34.9 %. The T1-S1 length
      increased from 26.3 to 34.7 cm at final follow-up. Especially, one of the type I
      SSCM patients whose neurological deterioration was found preoperatively was
      significantly improved. CONCLUSION: Preoperative Halo-gravity traction followed
      by non-fusion and growing instrumentation may be effective and safe for young
      children of CSD associated with SSCM. But it is an ongoing study and additional
      large multicenter studies are necessary to further assess the safety and efficacy
      of non-fusion and growing instrumentation.

PMID- 23558580
TI  - Characterizing the need for tracheostomy placement and decannulation after
      cervical spinal cord injury.
AB  - PURPOSE: There have been few reports on the risk factors for tracheostomy and the
      possibility of patients for decannulation. The purpose of this study was to
      identify factors necessitating tracheostomy after cervical spinal cord injury
      (SCI) and detect features predictive of successful decannulation in tracheostomy
      patients. METHODS: One hundred and sixty four patients with cervical
      fracture/dislocation were retrospectively reviewed. The patients comprised 142
      men and 22 women with a mean age of 44.9 years. The clinical records were
      reviewed for patients' demographic data, smoking history, level of cervical spine
      injury, injury patterns, neurological status, evidence of direct thoracic trauma
      and head injury, tracheostomy placement, and decannulation. Risk factors
      necessitating tracheostomy and factors predicting decannulation were
      statistically analysed. RESULTS: Twenty-five patients (15.2%) required
      tracheostomy. Twenty-one patients were successfully decannulated. Smoking history
      (relative risk [RR], 3.05; p = 0.03) and complete SCI irrespective of injury
      level (C1-4 complete SCI: RR, 67.55; p < 0.001, C5-7 complete SCI: RR, 57.88; p <
      0.001) were significant risk factors necessitating tracheostomy. C1-4 complete
      SCI was more frequent among those who could not be decannulated. However, even in
      patients with high cervical complete SCI at the time of injury, patients
      regaining sufficient movement to shrug their shoulders within 3 weeks after
      injury could later be decannulated. CONCLUSIONS: The risk factors for
      tracheostomy after complete SCI were a history of smoking and complete paralysis
      irrespective of the level of injury. High cervical level complete SCI was found
      to be a risk factor for the failure of decannulation in patients without shoulder
      shrug within 3 weeks after injury.

PMID- 23558581
TI  - Ethyl acetate as an acyl donor in the continuous flow kinetic resolution of (+/-)
      1-phenylethylamine catalyzed by lipases.
AB  - The synthesis of chiral amines is still a challenge for organic synthesis since
      optically pure amines are of great importance for the pharmaceutical and
      agrochemical industries. Among all the methodologies developed until now,
      chemoenzymatic dynamic kinetic resolution has proven to be useful for the
      preparation of enantioenriched primary chiral amines. In our continuous efforts
      toward the development of a continuous flow process, herein we report our results
      on the continuous flow kinetic resolution of (+/-)-1-phenylethylamine leading to
      the desired products with high enantiomeric ratios (>200) and short residence
      times (40 minutes) using ethyl acetate as the acyl donor.

PMID- 23558582
TI  - Pulmonary necrotizing granulomas of unknown cause: clinical and pathologic
      analysis of 131 patients with completely resected nodules.
AB  - BACKGROUND: The cause of pulmonary necrotizing granulomas is often unclear, even
      after histologic examination. Our aim was to determine the clinical significance
      of histologically unexplained necrotizing granulomas. METHODS: Pulmonary
      necrotizing granulomas surgically resected at the Mayo Clinic (1994-2004) were
      retrieved and reviewed retrospectively. Cases in which a cause was evident at the
      time of initial histologic examination were excluded. The analysis cohort
      comprised 131 completely resected histologically unexplained pulmonary
      necrotizing granulomas. Clinical and laboratory information was abstracted from
      medical records, chest CT scans were reviewed, histologic slides were reexamined,
      and additional ancillary studies were performed in selected cases. RESULTS: A
      cause was determined on review in more than one-half of the histologically
      unexplained necrotizing granulomas (79 of 131, 60%) by reexamining histologic
      slides (47), incorporating the results of cultures (26), fungal serologies (14),
      and other laboratory studies (eight), and correlating histologic findings with
      clinical and radiologic information (13). Infections accounted for the majority
      (64 of 79), the most common being histoplasmosis (37) and nontuberculous
      mycobacterial infections (18). Noninfectious diagnoses (15 of 79) were rheumatoid
      nodule (five), granulomatosis with polyangiitis (Wegener) (five), sarcoidosis
      (four), and chronic granulomatous disease (one). Many cases remained unexplained
      even after extensive review (52 of 131, 40%). Most of these patients received no
      medical therapy and did not progress clinically or develop new nodules (median
      follow-up, 84 months). CONCLUSIONS: A cause, the most common being infection, can
      be established in many surgically resected pulmonary necrotizing granulomas that
      appear unexplained at the time of initial histologic diagnosis. Patients whose
      granulomas remain unexplained after a rigorous review have a favorable outcome.
      Most do not develop new nodules or progress clinically, even without medical
      therapy.

PMID- 23558583
TI  - Two-day detection of infectious enteric and non-enteric adenoviruses by improved
      ICC-qPCR.
AB  - In order to provide a more suitable response to public health concerns, we
      improved the detection of infectious human adenoviruses in water by optimising
      the commonly used integrated cell culture-PCR method. Risk evaluation studies
      seek for rapid detection of infectious adenoviruses, including the enteric types
      40 and 41 that are considered as the second most common agents of gastroenteritis
      in children next to rotaviruses. The here-employed 293A cell line used for
      infectious status assessment showed its ability to multiply adenoviruses
      including type 41. Two modifications were moreover applied to the workflow for
      viral detection. The first occurred at the nucleic acid extraction step performed
      directly on all infected cells, while the second was the application of real-time
      quantitative PCR as detection tool. All adaptations led to a 3-day reduction of
      the response delay and an improved sensitivity especially for the enteric
      adenoviral types. The infectious status of laboratory strain types 2 and 41 was
      demonstrated by a more than 2-log10 increase in genome quantity. These
      conclusions were confirmed and reinforced by the analysis of water samples
      applying the improved assay. Naturally occurring infectious adenoviruses were
      detected in wastewater and river water, within 2 days. Types belonging to the
      species human adenoviruses C and type 31 were observed, but the most frequently
      identified type was 41 (71 % of identified sequences, n = 34). This highlights
      the usefulness of our method for a wide range of types, and especially for the
      most prevalent and public health-relevant enteric adenoviruses.

PMID- 23558585
TI  - Improvement of NADPH bioavailability in Escherichia coli through the use of
      phosphofructokinase deficient strains.
AB  - NADPH-dependent reactions play important roles in production of industrially
      valuable compounds. In this study, we used phosphofructokinase (PFK)-deficient
      strains to direct fructose-6-phosphate to be oxidized through the pentose
      phosphate pathway (PPP) to increase NADPH generation. pfkA or pfkB single
      deletion and double-deletion strains were tested for their ability to produce
      lycopene. Since lycopene biosynthesis requires many NADPH, levels of lycopene
      were compared in a set of isogenic strains, with the pfkA single deletion strain
      showing the highest lycopene yield. Using another NADPH-requiring process, a one
      step reduction reaction of 2-chloroacrylate to 2-chloropropionic acid by 2
      haloacrylate reductase, the pfkA pfkB double-deletion strain showed the highest
      yield of 2-chloropropionic acid product. The combined effect of glucose-6
      phosphate dehydrogenase overexpression or lactate dehydrogenase deletion with PFK
      deficiency on NADPH bioavailability was also studied. The results indicated that
      the flux distribution of fructose-6-phosphate between glycolysis and the pentose
      phosphate pathway determines the amount of NAPDH available for reductive
      biosynthesis. 

PMID- 23558586
TI  - Myelin in development and disease.

PMID- 23558584
TI  - Bacterial polycyclic aromatic hydrocarbon ring-hydroxylating dioxygenases in the
      sediments from the Pearl River estuary, China.
AB  - Bacterial community compositions were characterized using denaturing gradient gel
      electrophoresis analysis of bacterial 16S rRNA gene in the sediments of the Pearl
      River estuary. Sequencing analyses of the excised bands indicated that Gram
      negative bacteria, especially Gammaproteobacteria, were dominant in the Pearl
      River estuary. The diversity of polycyclic aromatic hydrocarbon ring
      hydroxylating dioxygenase (PAH-RHD) gene in this estuary was then assessed by
      clone library analysis. The phylogenetic analyses showed that all PAH-RHD gene
      sequences of Gram-negative bacteria (PAH-RHD[GN]) were closely related to the
      nagAc gene described for Ralstonia sp. U2 or nahAc gene for Pseudomonas sp. 9816
      4, while the PAH-RHD gene sequences of Gram-positive bacteria (PAH-RHD[GP]) at
      sampling site A1 showed high sequence similarity to the nidA gene from
      Mycobacterium species. Meanwhile, molecular diversity of the two functional genes
      was higher at the upstream of this region, while lower at the downstream.
      Redundancy analysis indicated that environmental factors, such as NH4--N, ?PAHs,
      pH, SiO3--Si, and water depth, affected the distribution of the PAH-RHD[GN] gene
      in the Pearl River estuary.

PMID- 23558587
TI  - Promoting remyelination for the treatment of multiple sclerosis: opportunities
      and challenges.
AB  - Multiple sclerosis (MS) is a chronic and devastating autoimmune demyelinating
      disease of the central nervous system. With the increased understanding of the
      pathophysiology of this disease in the past two decades, many disease-modifying
      therapies that primarily target adaptive immunity have been shown to prevent
      exacerbations and new lesions in patients with relapsing-remitting MS. However,
      these therapies only have limited efficacy on the progression of disability.
      Increasing evidence has pointed to innate immunity, axonal damage and neuronal
      loss as important contributors to disease progression. Remyelination of denuded
      axons is considered an effective way to protect neurons from damage and to
      restore neuronal function. The identification of several key molecules and
      pathways controlling the differentiation of oligodendrocyte progenitor cells and
      myelination has yielded clues for the development of drug candidates that
      directly target remyelination and neuroprotection. The long-term efficacy of this
      strategy remains to be evaluated in clinical trials. Here, we provide an overview
      of current and emerging therapeutic concepts, with a focus on the opportunities
      and challenges for the remyelination approach to the treatment of MS.

PMID- 23558588
TI  - Polarization of macrophages and microglia in inflammatory demyelination.
AB  - Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central
      nervous system, and microglia and macrophages play important roles in its
      pathogenesis. The activation of microglia and macrophages accompanies disease
      development, whereas depletion of these cells significantly decreases disease
      severity. Microglia and macrophages usually have diverse and plastic phenotypes.
      Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS
      and its animal model, experimental autoimmune encephalomyelitis. The polarization
      of microglia and macrophages may underlie the differing functional properties
      that have been reported. in this review, we discuss the responses and
      polarization of microglia and macrophages in MS, and their effects on its
      pathogenesis and repair. Harnessing their beneficial effects by modulating their
      polarization states holds great promise for the treatment of inflammatory
      demyelinating diseases.

PMID- 23558589
TI  - Signaling mechanisms regulating myelination in the central nervous system.
AB  - The precise and coordinated production of myelin is essential for proper
      development and function of the nervous system. Diseases that disrupt myelin,
      including multiple sclerosis, cause significant functional disability. Current
      treatment aims to reduce the inflammatory component of the disease, thereby
      preventing damage resulting from demyelination. However, therapies are not yet
      available to improve natural repair processes after damage has already occurred.
      A thorough understanding of the signaling mechanisms that regulate myelin
      generation will improve our ability to enhance repair. in this review, we
      summarize the positive and negative regulators of myelination, focusing primarily
      on central nervous system myelination. Axon-derived signals, extracellular
      signals from both diffusible factors and the extracellular matrix, and
      intracellular signaling pathways within myelinating oligodendrocytes are
      discussed. Much is known about the positive regulators that drive myelination,
      while less is known about the negative regulators that shift active myelination
      to myelin maintenance at the appropriate time. Therefore, we also provide new
      data on potential negative regulators of CNS myelination.

PMID- 23558592
TI  - Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated
      magnetic nanoparticles.
AB  - Nanotechnology is a promising alternative to overcome the limitations of
      classical chemotherapy. As a novel approach, dendrimer-coated magnetic
      nanoparticles (DcMNPs) maintain suitable drug delivery system because of their
      buildup of functional groups, symmetry perfection, nanosize, and internal
      cavities. They can also be targeted to the tumor site in a magnetic field. The
      aim of this study is to obtain an effective targeted delivery system for
      doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G2 , G3
      , G4 , and G7 ) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release,
      and stability efficiencies in these nanoparticles (NPs) were studied. The results
      showed that low-generation NPs obtained in this study have pH-sensitive drug
      release characteristics. G4 DcMNP, which releases most of the drug in lower pH,
      seems to be the most suitable generation for efficient Doxorubicin delivery.
      Furthermore, application of doxorubicin-loaded G4 DcMNPs may help to overcome
      doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3 DcMNPs would be
      suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong
      JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390-1427.) and taxenes (Clarke SJ,
      Rivory LP. 1999. Clin Pharmacokinet 36(2):99-114.), which show their effects in
      cytoplasm. The results of this study can provide new insights in the development
      of pH-sensitive targeted drug delivery systems to overcome drug resistance during
      cancer therapy.

PMID- 23558590
TI  - Oligodendroglia and neurotrophic factors in neurodegeneration.
AB  - Myelination by oligodendroglial cells (OLs) enables the propagation of action
      potentials along neuronal axons, which is essential for rapid information flow in
      the central nervous system. Besides saltatory conduction, the myelin sheath also
      protects axons against inflammatory and oxidative insults. Loss of myelin results
      in axonal damage and ultimately neuronal loss in demyelinating disorders.
      However, accumulating evidence indicates that OLs also provide support to neurons
      via mechanisms beyond the insulating function of myelin. More importantly, an
      increasing volume of reports indicates defects of OLs in numerous
      neurodegenerative diseases, sometimes even preceding neuronal loss in pre
      symptomatic episodes, suggesting that OL pathology may be an important mechanism
      contributing to the initiation and/or progression of neurodegeneration. This
      review focuses on the emerging picture of neuronal support by OLs in the
      pathogenesis of neurodegenerative disorders through diverse molecular and
      cellular mechanisms, including direct neuron-myelin interaction, metabolic
      support by OLs, and neurotrophic factors produced by and/or acting on OLs.

PMID- 23558591
TI  - Cuprizone-induced demyelination in mice: age-related vulnerability and
      exploratory behavior deficit.
AB  - Schizophrenia is a mental disease that mainly affects young individuals (15 to 35
      years old) but its etiology remains largely undefined. Recently, accumulating
      evidence indicated that demyelination and/or dysfunction of oligodendrocytes is
      an important feature of its pathogenesis. We hypothesized that the vulnerability
      of young individuals to demyelination may contribute to the onset of
      schizophrenia. In the present study, three different age cohorts of mice, i.e.
      juvenile (3 weeks), young-adult (6 weeks) and middle-aged (8 months), were
      subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal
      model of acute demyelination. Then, age-related vulnerability to CPZ-induced
      demyelination, behavioral outcomes, and myelination-related molecular biological
      changes were assessed. We demonstrated: (1) CPZ treatment led to more severe
      demyelination in juvenile and young-adult mice than in middle-aged mice in the
      corpus callosum, a region closely associated with the pathophysiology of
      schizophrenia; (2) the higher levels of demyelination in juvenile and young-adult
      mice were correlated with a greater reduction of myelin basic protein, more loss
      of CC-1-positive mature oligodendrocytes, and higher levels of astrocyte
      activation; and (3) CPZ treatment resulted in a more prominent exploratory
      behavior deficit in juvenile and young-adult mice than in middle-aged mice.
      Together, our data demonstrate an age-related vulnerability to demyelination with
      a concurrent behavioral deficit, providing supporting evidence for better
      understanding the susceptibility of the young to the onset of schizophrenia.

PMID- 23558593
TI  - Fine-scale signatures of molecular evolution reconcile models of indel-associated
      mutation.
AB  - Genomic structural alterations that vary within species, known as large copy
      number variants, represent an unanticipated and abundant source of genetic
      diversity that associates with variation in gene expression and susceptibility to
      disease. Even short insertions and deletions (indels) can exert important effects
      on genomes by locally increasing the mutation rate, with multiple mechanisms
      proposed to account for this pattern. To better understand how indels promote
      genome evolution, we demonstrate that the single nucleotide mutation rate is
      elevated in the vicinity of indels, with a resolution of tens of base pairs, for
      the two closely related nematode species Caenorhabditis remanei and C. sp. 23. In
      addition to indels being clustered with single nucleotide polymorphisms and fixed
      differences, we also show that transversion mutations are enriched in sequences
      that flank indels and that many indels associate with sequence repeats. These
      observations are compatible with a model that reconciles previously proposed
      mechanisms of indel-associated mutagenesis, implicating repeat sequences as a
      common driver of indel errors, which then recruit error-prone polymerases during
      DNA repair, resulting in a locally elevated single nucleotide mutation rate. The
      striking influence of indel variants on the molecular evolution of flanking
      sequences strengthens the emerging general view that mutations can induce further
      mutations.

PMID- 23558594
TI  - Rewriting evolution--"been there, done that".
AB  - A recent paper by a science journalist in Nature shows major errors in
      understanding phylogenies, in this case of placental mammals. The underlying
      unrooted tree is probably correct, but the placement of the root just reflects a
      well-known error from the acceleration in the rate of evolution among some
      myomorph rodents.

PMID- 23558595
TI  - Colonic stent placement: a "double contrast technique": slightly novel approach.

PMID- 23558597
TI  - Imaging in patients with obstructed defecation.

PMID- 23558596
TI  - MR-defecography in obstructed defecation syndrome (ODS): technique, diagnostic
      criteria and grading.
AB  - BACKGROUND: The aim of this study was to evaluate the use of a magnetic resonance
      (MR)-based classification system of obstructive defecation syndrome (ODS) to
      guide physicians in patient management. METHODS: The medical records and imaging
      series of 105 consecutive patients (90 female, 15 male, aged 21-78 years, mean
      age 46.1 +/- 5.1 years) referred to our center between April 2011 and January
      2012 for symptoms of ODS were retrospectively examined. After history taking and
      a complete clinical examination, patients underwent MR imaging according to a
      standard protocol using a 0.35 T permanent field, horizontally oriented open
      configuration magnet. Static and dynamic MR-defecography was performed using
      recognized parameters and well-established diagnostic criteria. RESULTS: Sixty
      seven out of 105 (64 %) patients found the prone position more comfortable for
      the evacuation of rectal contrast while 10/105 (9.5 %) were unable to empty their
      rectum despite repeated attempts. Increased hiatus size, anterior rectocele and
      focal or extensive defects of the levator ani muscle were the most frequent
      abnormalities (67.6, 60.0 and 51.4 %, respectively). An MR-based classification
      was developed based on the combinations of abnormalities found: Grade 1 =
      functional abnormality, including paradoxical contraction of the puborectalis
      muscle, without anatomical defect affecting the musculo-fascial structures; Grade
      2 = functional defect associated with a minor anatomical defect such as rectocele
      <= 2 cm in size and/or first-degree intussusception; Grade 3 = severe defects
      confined to the posterior anatomical compartment, including >2 cm rectocele,
      second- or higher-degree intussusception, full-thickness external rectal
      prolapse, poor mesorectal posterior fixation, rectal descent >5 cm, levator ani
      muscle rupture, ballooning of the levator hiatus and focal detachment of the
      endopelvic fascia; Grade 4 = combined defects of two or three pelvic floor
      compartments, including cystocele, hysterocele, enlarged urogenital hiatus,
      fascial tears enterocele or peritoneocele; Grade 5 = changes after failed
      surgical repair abscess/sinus tracts, rectal pockets, anastomotic strictures,
      small uncompliant rectum, kinking and/or lateral shift of supra-anastomotic
      portion and pudendal nerve entrapment. CONCLUSIONS: According to our
      classification, Grades 1 and 2 may be amenable to conservative therapy; Grade 3
      may require surgical intervention by a coloproctologist; Grade 4 would need a
      combined urogynecological and coloproctological approach; and Grade 5 may require
      an even more complex multidisciplinary approach. Validation studies are needed to
      assess whether this MR-based classification system leads to a better management
      of patients with ODS.

PMID- 23558598
TI  - A "patient-tailored" treatment of hypertension with use of impedance
      cardiography: a randomized, prospective and controlled trial.
AB  - BACKGROUND: Arterial hypertension might be caused by hemodynamic disturbances
      such as fluid retention, increased vascular resistance, and hyperdynamic function
      of the heart. The aim of this study was to estimate the effectiveness of
      antihypertensive therapy based on hemodynamic assessment by impedance
      cardiography in a randomized, prospective, controlled trial. MATERIAL AND
      METHODS: This study involved 128 patients (average age: 42.9 +/- 11.1 years) with
      arterial hypertension, randomized into groups: (1) empiric, and (2) hemodynamic,
      in which treatment choice considered impedance cardiography results. Evaluation
      of treatment effects was performed after 12 weeks and included office blood
      pressure measurement and ambulatory blood pressure monitoring. RESULTS: All final
      blood pressure values were lower in the hemodynamic group, significantly for
      office systolic blood pressure (empiric vs. hemodynamic: 136.1 vs. 131.6 mmHg;
      p=0.036) and diastolic blood pressure (87.0 vs. 83.7 mmHg; p=0.013), as well as
      night-time systolic blood pressure (121.3 vs. 117.2 mmHg; p=0.023) and diastolic
      blood pressure (71.9 vs. 68.4 mmHg; p=0.007). Therapy based on impedance
      cardiography significantly increased the reduction in office systolic blood
      pressure (11.0 vs. 17.3 mmHg; p=0.008) and diastolic blood pressure (7.7 vs. 12.2
      mmHg; p=0.0008); as well as 24-h mean systolic blood pressure (9.8 vs. 14.2 mmHg;
      p=0.026), daytime systolic blood pressure (10.5 vs. 14.8 mmHg; p=0.040), and
      night-time systolic blood pressure (7.7 vs. 12.2 mmHg; p=0.032). CONCLUSIONS:
      Antihypertensive treatment based on impedance cardiography can significantly
      increase blood pressure reduction in hypertensive patients.

PMID- 23558600
TI  - Lixisenatide: first global approval.
AB  - The selective once-daily prandial glucagon-like peptide-1 (GLP-1) receptor
      agonist lixisenatide (Lyxumia((r))) is under development with Sanofi for the
      treatment of type 2 diabetes mellitus. Lixisenatide belongs to a class of GLP-1
      compounds designed to mimic the endogenous hormone GLP-1. Native GLP-1 stimulates
      insulin secretion in a glucose-dependent manner, as well as suppressing glucagon
      production and slowing gastric emptying. A once-daily subcutaneous formulation of
      lixisenatide has been approved in the EU, Iceland, Liechtenstein, Norway and
      Mexico for the treatment of type 2 diabetes, and is under regulatory review in
      the USA, Switzerland, Brazil, Canada, Ukraine, South Africa, Japan and Australia.
      This article summarizes the milestones in the development of lixisenatide,
      leading to this first approval for use in adults with type 2 diabetes.

PMID- 23558599
TI  - Exercise capacity, muscle strength, and fatigue in sarcoidosis: a follow-up
      study.
AB  - PURPOSE: The purpose of this study was to examine changes in the prevalence of
      exercise intolerance, reduced muscle strength, and fatigue and the changes in
      these parameters in individual patients during a 2-year follow-up study. METHODS:
      Ninety sarcoidosis patients (62 males and 28 females; mean age: 46.0 +/- 10.2
      years) participated in a 2-year follow-up study. At the baseline and follow-up
      measurements, patients performed a 6-min walk test and elbow flexor muscle
      strength, quadriceps peak torque, and hamstrings peak torque tests. Maximal
      inspiratory pressure was recorded. All patients completed the Fatigue Assessment
      Scale. RESULTS: Both at baseline and follow-up, a substantial proportion of the
      patients showed a reduced 6-minute walk test (41.6 and 34.8 %, respectively),
      elbow flexor muscle strength (6.7 and 14.6 %), quadriceps peak torque (21.3 and
      18 %), hamstrings peak torque (13.5 and 12.4 %), and maximal inspiratory pressure
      (45.9 and 48.6 %). The majority of the patients reported fatigue (86 and 77 %).
      These physical impairments remained stable during the follow-up period. The
      prevalence of these physical impairments in patients diagnosed with sarcoidosis
      <2 years before inclusion in this study was similar to that in patients with a
      longer history of the disease. CONCLUSIONS: Exercise intolerance, muscle
      weakness, and fatigue are frequent problems in symptomatic sarcoidosis patients
      with a stable and persistent character. This study highlights that beyond medical
      treatment a rehabilitation program should be considered as adjunct therapy in the
      multidisciplinary management of sarcoidosis patients even though the achieved
      benefit needs future studies.

PMID- 23558601
TI  - Effect of carbamazepine on the pharmacokinetic parameters of CDRI-97/78 following
      coadministration to rats.
AB  - Coadministration of 2 or more drugs may result in unexpected toxicity. This study
      aimed to evaluate the effect of carbamazepine coadministration on the
      pharmacokinetics of CDRI-97/78, an 1,2,4-trioxane antimalarial agent. Firstly,
      97/78 was administered alone and then 97/78 and carbamazepine were coadministered
      to male and female rats. An revalidated LC-MS/MS method was used for quantitation
      of 97/63 since 97/78 is instantly and completely converted to 97/63 (an in-vivo
      active metabolite). The Tmax and Cmax values of 97/63 were 1.75+/-0.77 h and
      862+/-306 ng/mL in male rats whereas in female rats they were 5.45+/-0.76 h and
      662.75+/-95.09 ng/mL after a single dose of 97/78 alone. However, following
      coadministration of 97/78 and carbamazepine, the values for Tmax and Cmax were
      1.06+/-0.16 h and 533+/-153 ng/mL in male rats and 2.23+/-1.93 h and 636.5+/
      112.4 ng/mL in female rats. The half life of 97/63 following a single oral dose
      of 97/78 or coadministration with carbamazepine to male rats was 6.98+/-0.63 h
      and 6.64+/-0.54 h, respectively; the values in female rats were 7.5+/-0.5 h and
      5.48+/-0.37 h. A statistically insignificant difference (P>0.05) was observed
      with the student t-test for the pharmacokinetic parameters of 97/63 following
      oral administration of 97/78 alone or coadministration of 97/78 and carbamazepine
      except for MRT in female rats. Intersex statistical comparison also showed an
      insignificant difference for 97/63 following oral administration of 97/78 alone
      or in combination with carbamazepine except for MRT, which supports
      coadministration of 97/78 and carbamazepine. 

PMID- 23558602
TI  - Pharmacokinetics of a new immediate-release compound omeprazole capsule and its
      comparison with the enteric-coated formulation under fasting and fed conditions.
AB  - The present study was conducted to describe the pharmacokinetic profile of
      immediate-release compound omeprazole capsule and compare it with the enteric
      coated formulation under fasting and fed condition.This study was designed to
      phase I, open-label, randomized, 3-part clinical trial. 12 subjects in part one
      received single doses (20 mg and 40 mg) and repeated doses (20 mg). Different 30
      subjects in part 2 (fasting condition) and part 3 (fed condition) received either
      compound omeprazole capsule (40 mg) or delayed-release omeprazole (40 mg)
      separated by 7 days.Compound omeprazole capsule showed dose non-proportionality
      in the range from 20 mg to 40 mg. The AUC0-t of 20 mg omeprazole is 78% higher
      after repeated doses. The C max was higher and T max was lower for compound
      omeprazole capsule than delayed-release omeprazole. 90% CIs for AUC0-t of the 2
      periods (test/reference) under fasting and fed conditions were 106.3%
      (102.2%~109.2%) and 104.1% (93.4%~109.6%), respectively. Presence of food reduced
      the rate (C max) and extent (AUC0-t) of systemic exposure of the test and
      reference formulations from 1 462 to 777 ng . mL-1, 1 055 to 602 ng . mL-1, 2 597
      to 1 852 ng . h . mL-1 and 2 454 to 1 873 ng . h . mL-1, respectively.Exposed
      dose of omeprazole in subjects with compound omeprazole capsule was time- and
      dose-dependent. Compared with delayed-release omeprazole, compound omeprazole
      capsule had rapid but similar degree of absorption of omeprazole. 

PMID- 23558603
TI  - Non-inferiority trial between two dry-powder inhalers containing
      fluticasone/salmeterol in asthmatic patients.
AB  - Asthma is an increasing pathology with poor compliance. Achievement of control is
      possible but under intensive treatment. In this setting, fluticasone/salmeterol
      association delivered by dry powder inhalers is a valuable and proved option. A
      prospective, parallel, open-label, phase IV, multicentre non-inferiority study
      was conducted to determine therapeutic similarity between 2 different inhalers:
      Generic DPI and Diskus(r), which both deliver a fluticasone/salmeterol
      association (CAS 80474-14-2/CAS 89365-50-4). A 103 uncontrolled asthmatic
      patients were randomly assigned in 2 groups, Generic (G) and Diskus(r) (D), and
      received the association for 18 weeks through the appropriate device. They were
      evaluated according to Asthma Quality of Life Questionnaire and GINA/NIH
      guidelines. To demonstrate non-inferiority, the estimation of the Relative Risk
      between the Global Score Rate per group with its 95% confidence interval was
      calculated and compared against a non-inferiority margin obtained from a previous
      study. The Global Score Rate was 82% for G Group and 83% for D Group. The RR was
      1.0124 (95% CI: 0.847-1.210). The margin set at 0.832 was not reached by the
      lower 95% CI (z=-2.097; p=0.018) pointing out non-inferiority. The results have
      demonstrated non-inferiority between groups. Thus, the 2 products are
      therapeutically similar. 

PMID- 23558605
TI  - Of men, not mice.

PMID- 23558604
TI  - Effects of twin block appliance on obstructive sleep apnea in children: a
      preliminary study.
AB  - BACKGROUND: Oral appliances are increasingly advocated as a treatment option for
      obstructive sleep apnea (OSA). However, it is not clear how the different designs
      influence treatment efficacy in children. The aim of this study was to
      investigate the effects of twin block (TB) appliance on children with OSA and
      mandibular retrognathia. METHODS: A total of 46 children (31 males, 15 females,
      aged 9.7 +/- 1.5 years, BMI: 18.1 +/- 1.04 kg/m(2)) diagnosed with mandibular
      retrognathia and OSA by polysomnography (PSG) and with no obesity or
      adenotonsillar hypertrophy were recruited for the study. Patients in the
      treatment group were instructed to wear the twin block oral appliance full time
      for an average of 10.8 months. The efficacy of treatment was determined by
      monitoring the PSG and cephalometric changes before and after appliance removal.
      Data were analyzed using paired t test. RESULTS: Results showed an improvement in
      patient's facial profile after treatment with the TB appliance. The average AHI
      index decreased from 14.08 +/- 4.25 to 3.39 +/- 1.86 (p < 0.01), and the lowest
      SaO2 increased from 77.78 +/- 3.38 to 93.63 +/- 2.66 (p < 0.01). Cephalometric
      measurements showed a significant increase in the superior posterior airway
      space, middle airway space, SNB angle and facial convexity which indicate an
      enhancement in mandibular growth, and reduction in the soft palate length.
      CONCLUSIONS: This preliminary study suggests that twin block appliance may
      improve the patient's facial profile and OSA symptoms in a group of carefully
      selected children presented with both OSA and mandibular retrognathia symptoms.

PMID- 23558606
TI  - New, intensive trials planned on heels of Mississippi HIV 'cure'.

PMID- 23558608
TI  - Manufacturers push the limits of megacombo vaccines for kids.

PMID- 23558609
TI  - New yardstick could speed access to cancer drugs for surgery.

PMID- 23558610
TI  - Underestimate of HIV reservoirs threatens purging approach.

PMID- 23558611
TI  - Regulatory agency struggles under the weight of genomic data.

PMID- 23558613
TI  - Under scrutiny, India's medical research council faces review.

PMID- 23558614
TI  - Straight talk with...Miyoung Chun. Interview by Virginia Hughes.
AB  - It was a single tweet. In February, after US President Barack Obama made a subtle
      nod to a new neuroscience project in his annual State of the Union address,
      Francis Collins, director of the country's National Institutes of Health (NIH),
      posted on the @NIHDirector Twitter feed: "Obama mentions the #NIH Brain Activity
      Map in #SOTU." Instantly, scientists were buzzing with rumors that the Brain
      Activity Map could be the next moon shot, with a budget and timeline similar to
      the Human Genome Project. The brain map began as a brief white paper and has
      grown into a large--and still largely undefined--collaboration of several
      government agencies, nonprofit foundations and private companies. As the
      stakeholders describe in a commentary published last month (339, 1284-1285,
      2013), the goal of the initiative is to understand how thousands of neurons work
      in concert to control behavior and trigger disease. Miyoung Chun, vice president
      for science programs at The Kavli Foundation in Oxnard, California, has been
      developing the project since the beginning and is the self-described "glue"
      between its many diverse stakeholders. Chun spoke with Virginia Hughes about the
      evolution of the project and what it might mean for biomedicine.

PMID- 23558616
TI  - Natural products emergent.

PMID- 23558617
TI  - Natural-born scientists.

PMID- 23558619
TI  - Circulating fetuin-A and free fatty acids interact to predict insulin resistance
      in humans.

PMID- 23558620
TI  - Systematic reviews deserve more credit than they get.

PMID- 23558621
TI  - Antigen depots: T cell traps?

PMID- 23558622
TI  - Exploring the erythroblastic island.

PMID- 23558623
TI  - Love the one you're with: the HIV, B cell and TFH cell triangle.

PMID- 23558624
TI  - Blocking bleeding: reversing anticoagulant therapy.

PMID- 23558625
TI  - Sorting receptors at Down's syndrome synapses.

PMID- 23558626
TI  - Coagulation factor defends adenovirus from immune attack.

PMID- 23558627
TI  - Metabolic reprogramming in polycystic kidney disease.

PMID- 23558628
TI  - Bettering BCG: a tough task for a TB vaccine?

PMID- 23558629
TI  - Is heart regeneration on the right track?

PMID- 23558630
TI  - Heart repair by cardiac reprogramming.

PMID- 23558640
TI  - Diastereotopic fluorine substituents as 19F NMR probes of screw-sense preference
      in helical foldamers.
AB  - Ligating simple amino alcohol or amino ester monomers containing enantiotopic
      fluorine substituents to the C-terminus of a helical peptide places the fluorine
      atoms in diastereotopic environments, and gives two distinct and easily
      identifiable signals in the (19)F NMR spectrum. In the case of a dynamically
      inverting helix built from achiral monomers, the chemical shift separation
      between the (19)F signals provides a simple means of analysing the ratio of screw
      sense conformers in the oligomer, in cases where an asymmetric bias leads to a
      screw-sense preference.

PMID- 23558641
TI  - Functional linkages between replication proteins of genes 1, 3 and 5 of Bacillus
      subtilis phage phi29.
AB  - Gene 1 product (gp1) of Bacillus subtilis phage phi29 has been shown to be
      involved in viral DNA replication in vivo, but the essential role is still
      unknown. As part of an ongoing effort to understand the role of gp1 in viral DNA
      replication, we investigated genetic interaction between gene 1 and other viral
      genes. Because phi29 mutants which do not produce functional gp1 show temperature
      sensitive growth, we isolated temperature-resistant phages from the phi29 gene 1
      mutants, and eventually, obtained nine extragenic suppressors. These suppressor
      mutations were located in two essential genes for phi29 DNA replication in vivo:
      gene 3 encoding terminal/primer protein (gp3) or gene 5 encoding viral single
      stranded DNA binding protein (gp5). Most of these mutations resulted in single
      amino acid substitutions in the products. By trans-complementation assay, we
      confirmed that the absence of gp1 at non-permissive temperature can be
      compensated by the suppressors which have the single amino acid substitution in
      either gp5 or gp3. These results indicate that gp1 has functional relationship to
      gp5 and gp3. From the positions of amino acid substitutions in gp3, we propose
      its new regulatory subdomain at which other molecules including gp1 would
      interact with and regulate functions of gp3.

PMID- 23558639
TI  - Predictive value of outcome scores in patients suffering from cardiogenic shock
      complicating AMI: APACHE II, APACHE III, Elebute-Stoner, SOFA, and SAPS II.
AB  - BACKGROUND: Scoring systems in critical care patients are essential for
      prediction of outcome and for evaluation of therapy. In this study we determined
      the value of the APACHE II, APACHE III, Elebute-Stoner, SOFA, and SAPS II scoring
      systems in the prediction of mortality in patients with cardiogenic shock (CS)
      complicating acute myocardial infarction (AMI). MATERIAL AND METHODS: In this
      prospective, observational study, patients who were admitted to the ICU with CS
      complicating AMI were consecutively included. Data for the APACHE II, APACHE III,
      Elebute-Stoner, SOFA, and SAPS II scores were recorded on admission and during
      the following 96 h. Receiver operating characteristic curve analyses and the area
      under the curve (AUC) were used to estimate the predictive ability (mortality) of
      the scoring systems on admission and the maximum value. RESULTS: Mortality among
      the 41 patients included in this study was 44 %. On admission, the mean APACHE II
      (p = 0.035), APACHE III (p = 0.003), SAPS II (p = 0.001), and SOFA (p = 0.042)
      scores were significantly higher in nonsurvivors than in survivors. At maximum
      score, APACHE II (p = 0.009), APACHE III (p < 0.001), and SAPS II (p < 0.001)
      appeared to have higher significance. On admission, the discrimination for APACHE
      III was 0.786, for SAPS II 0.790, and for APACHE II 0.691. The maximum-score AUC
      for APACHE II was 0.726, for APACHE III 0.827, and for SAPS II 0.832. Elebute
      Stoner and SOFA did not yield valuable results at maximum score or, in the case
      of Elebute-Stoner, on admission. CONCLUSION: These results suggest that at the
      time of diagnosis and at maximum value, the SAPS II, APACHE III, and APACHE II
      scores may be useful in predicting a high probability of survival of patients
      with CS complicating AMI.

PMID- 23558642
TI  - A wheat homologue of PHYTOCLOCK 1 is a candidate gene conferring the early
      heading phenotype to einkorn wheat.
AB  - An X-ray mutant showing an early flowering phenotype has been identified in
      einkorn wheat (Triticum monococcum L.), for which a major QTL for heading time
      was previously mapped in the telomeric region on the long arm of chromosome 3A.
      Recent advances in Triticeae genomics revealed that the gene order in this region
      is highly conserved between wheat and barley. Thus, we adopted a hypothetical
      gene order in barley, the so-called GenomeZipper, to develop DNA markers for fine
      mapping the target gene in wheat. We identified three genes tightly linked to the
      early heading phenotype. PCR analysis revealed that early-flowering is associated
      with the deletion of two genes in the mutant. Of the two deleted genes, one is an
      ortholog of the LUX ARRHYTHMO (LUX)/PHYTOCLOCK 1 (PCL1) gene found in
      Arabidopsis, which regulates the circadian clock and flowering time. We found
      distorted expression patterns of two clock genes (TOC1 and LHY) in the einkorn
      pcl1 deletion mutant as was reported for the Arabidopsis lux mutant. Transcript
      accumulation levels of photoperiod-response related genes, a photoperiod
      sensitivity gene (Ppd-1) and two wheat CONSTANS-like genes (WCO1 and TaHd1), were
      significantly higher in the einkorn wheat mutant. In addition, transcripts of the
      wheat florigen gene (WFT) accumulated temporally under short-day conditions in
      the einkorn wheat mutant. These results suggest that deletion of WPCL1 leads to
      abnormally higher expression of Ppd-1, resulting in the accumulation of WFT
      transcripts that triggers flowering even under short-day conditions. Our
      observations from gene mapping, gene deletions, and expression levels of
      flowering related genes strongly suggest that WPCL1 is the most likely candidate
      gene for controlling the early flowering phenotype in the einkorn wheat mutant.

PMID- 23558646
TI  - Supramolecular H-bonded porous networks at surfaces: exploiting primary and
      secondary interactions in a bi-component melamine-xanthine system.
AB  - The control over the formation of a bi-component porous network was attained by
      the self-assembly at a solid-liquid interface by exploiting both primary and
      secondary non-covalent interactions between melamine and N(3)-alkylated xanthine
      modules. 

PMID- 23558647
TI  - ST2 as a cardiovascular risk biomarker: from the bench to the bedside.
AB  - ST2 is a member of the interleukin (IL)-1 receptor family discovered in a
      classical translational science fashion, and exists in two forms, a trans
      membrane receptor (ST2L) as well as a soluble decoy receptor (sST2). The ligand
      of ST2 is IL-33, which is involved in reducing fibrosis and hypertrophy in
      mechanically strained tissues. In in vitro and in vivo models, ST2L transduces
      the effects of IL-33, while excess sST2 or abnormalities in ST2 signaling leads
      to cardiac hypertrophy, fibrosis, and ventricular dysfunction. Clinically, in
      patients with symptomatic heart failure (HF), elevated concentrations of sST2 are
      strongly associated with severity of the diagnosis, and powerfully predict
      increased risk of complications, independent of other established or emerging
      biomarkers. sST2 testing has also been shown to predict onset of symptomatic HF
      in patients with acute myocardial infarction, while in community-based subjects,
      sST2 values independently predict future HF, cardiovascular disease events, and
      mortality. 

PMID- 23558648
TI  - A non-bacterial transcription factor inhibits bacterial transcription by a
      multipronged mechanism.
AB  - The process of transcription initiation is the major target for regulation of
      gene expression in bacteria and is performed by a multi-subunit RNA polymerase
      enzyme (RNAp). A complex network of regulatory elements controls the activity of
      the RNAp to fine-tune transcriptional output. Thus, RNAp is a nexus for
      controlling bacterial gene expression at the transcription level. Many
      bacteriophages, viruses that infect bacteria, encode transcription factors that
      specifically target and modulate the activity of the host RNAp and, thereby,
      facilitate the acquisition of the host bacteria by the phage. Here, we describe
      the modus operandi of a T7 bacteriophage-encoded small protein called Gp2 and
      define Gp2 as a non-bacterial regulator of bacterial transcription.

PMID- 23558650
TI  - Technical innovation in dynamic contrast-enhanced magnetic resonance imaging of
      musculoskeletal tumors: an MR angiographic sequence using a sparse k-space
      sampling strategy.
AB  - OBJECTIVE: We demonstrate the clinical use of an MR angiography sequence
      performed with sparse k-space sampling (MRA), as a method for dynamic contrast
      enhanced (DCE)-MRI, and apply it to the assessment of sarcomas for treatment
      response. MATERIALS AND METHODS: Three subjects with sarcomas (2 with
      osteosarcoma, 1 with high-grade soft tissue sarcomas) underwent MRI after
      neoadjuvant therapy/prior to surgery, with conventional MRI (T1-weighted, fluid
      sensitive, static post-contrast T1-weighted sequences) and DCE-MRI (MRA, time
      resolution = 7-10 s, TR/TE 2.4/0.9 ms, FOV 40 cm(2)). Images were reviewed by two
      observers in consensus who recorded image quality (1 = diagnostic, no significant
      artifacts, 2 = diagnostic, <25 % artifacts, 3 = nondiagnostic) and contrast
      enhancement characteristics by static MRI (presence/absence of contrast
      enhancement, percentage of enhancement) and DCE-MRI (presence/absence of arterial
      enhancement with time-intensity curves). Results were compared with histological
      response (defined as <5 % viable tumor [soft tissue sarcoma] or <10 % [bone
      sarcoma] following resection). RESULTS: Diagnostic quality for all conventional
      and DCE-MRI sequences was rated as 1. In 2 of the 3 sarcomas, there was good
      histological response (<=5 % viable tumor); in 1 there was poor response (50 %
      viable tumor). By static post-contrast T1-weighted sequences, there was
      enhancement in all sarcomas, regardless of response (up to >75 % with good
      response, >75 % with poor response). DCE-MRI findings were concordant with
      histological response (arterial enhancement with poor response, no arterial
      enhancement with good response). CONCLUSION: Unlike conventional DCE-MRI
      sequences, an MRA sequence with sparse k-space sampling is easily integrated into
      a routine musculoskeletal tumor MRI protocol, with high diagnostic quality. In
      this preliminary work, tumor enhancement characteristics by DCE-MRI were used to
      assess treatment response.

PMID- 23558651
TI  - Endovascular treatment of symptomatic true-lumen collapse of the downstream aorta
      after open surgery for acute aortic dissection type A.
AB  - AIM: The aim of the present study was to evaluate the outcome of endovascular
      treatment of true-lumen collapse (TLC) of the downstream aorta after open surgery
      for acute aortic dissection type A (AADA). METHODS: Retrospective, observational
      study with follow-up of 16 +/- 7.6 months. From April 2010 to January 2012, 89
      AADA-patients underwent aortic surgery. Out of these, computed tomography
      revealed a TLC of the downstream aorta in 13 patients (14.6%). They all received
      additional thoracic endovascular aortic repair (TEVAR) in consequence of
      malperfusion syndromes. RESULTS: In all 13 TLC-patients, dissection after AADA
      surgery extended from the aortic arch to the abdominal aorta and malperfusion
      syndromes occurred. Remodeling of the true-lumen was achieved by TEVAR with
      complemental stent disposal in abdominal and iliac arteries in all cases. One
      patient died on the third postoperative day due to intracerebral hemorrhage.
      Another patient, who presented under severe cardiogenic shock died despite AADA
      surgery and TEVAR-treatment. Thirty-day mortality was 15.4% in TLC-patients (N =
      2/13). In the follow-up period, 3 patients required additional aortic stents
      after the emergency TEVAR procedures. After 20 weeks, a third patient died
      secondary to malperfusion due to false-lumen recanalization. Therefore, late
      mortality was 23.1%. CONCLUSION: After proximal aortic repair for AADA, early
      postoperative computed tomography should be demanded in all patients to exclude a
      TLC of the descending aorta. Mortality is still substantial in these patients
      despite instant TEVAR application. Thus, in case of TLC and malperfusion syndrome
      of the downstream aorta, TEVAR should be performed early to alleviate or even
      prevent ischemic injury.

PMID- 23558652
TI  - Experience with early TEVAR treatment of uncomplicated type B aortic dissection.
AB  - The current paradigm for the treatment of chronic type B aortic dissection
      involves primarily medical treatment. The patients are then followed for sequelae
      like progressive dissection or aneurysmal degeneration, selecting this subgroup
      for further intervention. The European Collaborator Registry, the Talent Thoracic
      Retrospective Registry, and several meta-analysis showed that the uncomplicated
      type B dissection patients who underwent thoracic endovascular aortic repair
      (TEVAR) outperformed their counterpart in the complicated group. The INSTEAD
      trial, the first randomized trial to examine whether TEVAR is better than medical
      management in the chronic stable dissection patients, showed no benefit early on
      although mid-term data might show some benefit. Clearly more randomized
      controlled trials are necessary to create a paradigm shift. In the United States,
      the FDA approved TEVAR devices are for the descending thoracic aortic aneurysm
      and transection only. The use of these devices for dissection is off-label or for
      investigation only. As future study might broaden the use of TEVAR for the
      chronic dissection patients, the use of TEVAR in hybrid surgery and in the
      ascending aorta is also broadening the indication for this technology. With two
      decades of innovation behind, TEVAR will continue to evolve and innovate in the
      years ahead.

PMID- 23558653
TI  - New insights in (acute) endovascular abdominal aneurysm repair: when fenestrated
      devices fall short.
AB  - The suitability for endovascular aneurysm repair (EVAR) is determined primarily
      by abdominal aortic aneurysm (AAA) anatomy. For patients unsuitable for standard
      EVAR, due to proximal neck anatomy, fenestrated aortic stent-grafting (FEVAR) is
      a viable alternative to open repair surgery. Initially FEVAR stent-grafts were
      custom-made to fit the unique anatomical characteristics of each treated
      individual. This customization leads to production delays therefore excluding
      acute aneurysms from endovascular treatment. For patients in need for more urgent
      treatment, several alternatives have currently been developed. The aim of this
      review is to provide an overview on current developments and results in acute
      endovascular abdominal aortic aneurysm repair.

PMID- 23558654
TI  - Are concerns about EVAR durability relevant with modern devices?
AB  - Endovascular aneurysm repair (EVAR) is now universally adopted as first-line
      therapy for the management of large abdominal aortic aneurysms (AAA). The
      applicability has broadened such that up to 80% of patients are morphologically
      suitable for EVAR. In-spite of the evidence base demonstrating improved early
      outcomes following EVAR compared to open surgery, and informed patients'
      preference, EVAR-sceptics remain. The doubters voice anxieties regarding the
      durability of an endovascular repair and cite evidence of graft failures from the
      EVAR-1 trial results. Historically, graft migration and endoleak development have
      been the Achilles heel of EVAR. However, EVAR is an evolving technology that over
      the last 10 years has seen significant development from industry, and greater
      experience among clinicians. This has combined with centralisation of expertise
      in larger vascular units, with increased case-volume, leading to more appropriate
      periprocedural and long-term care. Current devices offer a durable repair for
      patients with infra-renal aortic aneurysms. The risk of graft migration is
      minimised by devices with secure fixation systems, potentially limiting de-novo
      type 1 and 3 endoleaks. Appropriate surveillance and timely endovascular re
      interventions are perhaps the most important factors to ensure robust long-term
      outcomes from endovascular repair, even when native vessel morphology changes.
      Industry registry evidence and large single unit case series are now generating a
      healthy evidence base of EVAR durability in contemporary endovascular practice,
      that affirms its role as first-line therapy in the majority of morphologically
      suitable patients.

PMID- 23558655
TI  - Unique demands of the femoral anatomy and pathology and the need for unique
      interventions.
AB  - With the aging of the population the incidence of peripheral artery disease (PAD)
      is increasing, which is histologically characterized by fibrocalcific intimal
      plaques as well as underlying Monckeberg's medial calcinosis as compared to
      coronary and carotid artery disease. Superficial femoral artery (SFA) is one of
      the longest and most dynamically active vessels in the body undergoing torsion,
      compression, flexion, and extension from leg motion, and is known to be more
      susceptible to atherosclerosis because of low shear stress or spiral flow, best
      appreciated in the long segment in its lesser curvature. Endovascular
      interventions are now considered the first-line strategy for the treatment of PAD
      patients presenting with claudication or critical limb ischemia, where
      physiologic stresses on the arterial wall, anatomic considerations, and lesion
      characteristics impact on their success. Stent fracture and malapposition, are a
      common phenomenon in PAD which are attributed to severe calcification and
      fibrosis along with greater motion of the lower extremity, that result in the
      dampening of the efficacy of stenting and balloon angioplasty. Better designs of
      self-expanding stents have resulted in either reduction in stent fracture rates
      or its elimination at least in the short-term follow-up studies, to date.
      Although drug-eluting stents (DES) have reduced restenosis rates in the coronary
      circulation, this benefit has not been consistently observed in PAD. However,
      recent clinical studies utilizing novel Zilver-PTX self-expanding stent (DES)
      have demonstrated favorable patency rate. Also, in patients with critical limb
      ischemia, better outcomes have been reported for below-the-knee utilization of
      DES. Nevertheless, drawbacks of stent technology remain and interests in the
      greater use of drug-coated balloons (DCB) for PAD have emerged. Randomized
      controlled trials have consistently shown superiority of DCB over uncoated
      balloons in reducing neointimal formation in patients with SFA disease. Moreover,
      there is a growing interest in atherectomy as an alternative treatment strategy
      for PAD, thus decreasing plaque burden with possibly avoidance of barotrauma. The
      results from registries support the effectiveness of the atherectomy devices;
      however, prospective randomized controlled trials are needed to confirm their
      benefit.

PMID- 23558656
TI  - Femoral stenting: what do the guidelines tell us.
AB  - Recommendations in guidelines should reflect current knowledge due to results of
      well-designed randomized clinical trials. However, one of the main problems with
      guidelines concerning revascularization in patients with peripheral arterial
      disease (PAD) is the lack of such clinical trials with a paucity of so called
      level I data. Furthermore, vascular interventions are practiced by physicians
      with different medical, surgical and radiologic speciality training background.
      An inter-society consensus statement by its very nature coalesces into one
      document the divergent experiences, interests and also interpretation of the
      literature by the participating parties, in our case mainly vascular surgeons and
      non-surgical interventionists. Therefore the recommendations in such
      international multi-societal consensus documents--such as the TASC document--are
      a compromise due to the necessity to be accepted by the different societies.
      Therefore often it remains difficult to follow such recommendations in clinical
      routine. A major problem of all guidelines is the problem of contemporaneity so
      that recent developments often cannot be included or discussed. Furthermore, in
      international guidelines no acknowledgement can be made of country- and/or center
      specific differences.

PMID- 23558657
TI  - Drug-eluting technologies in femoral artery lesions.
AB  - The treatment of femoropopliteal lesions has known an important evolution in the
      last years. An important limitation of current endovascular therapy remains the
      occurrence of restenosis. In order to minimize restenosis rates, drug eluting
      technologies are evolving. The use of drug-eluting stents (DES) in coronary
      arteries shows beneficial results, leading to investigation of DES in
      femoropopliteal arteries. In this article, we give an overview of current
      available data on treatment with drug eluting technologies in the superficial
      femoral artery (SFA). This paper summarizes also the current available data of
      the use of drug-coated balloons (DCB) in the femoropopliteal tract. Currently, no
      data are available on the use of DCB in long lesions. A drug eluting
      bioresorbable scaffold seems to be very promising in coronary arteries. The
      transfer to the peripheral area is nowadays ongoing. Which technique and device
      for which lesion and patient requires further investigation to build up a real
      evidence based SFA treatment strategy.

PMID- 23558658
TI  - Role of bioresorbable stents in the superficial femoral artery.
AB  - Bioresorbable stents or scaffolds are a new technology in the treatment of
      coronary and peripheral vascular disease. Their goal is to provide adequate
      support to the dilated vessel segment for the time needed and to disappear
      through a controlled resorption process afterwards. Doing so they can offer the
      early advantages and avoid the late complications related to stent placement such
      as stent-induced restenosis, stent fracture and problems at reintervention.
      Although the first implantation dates from more than ten years ago, this
      technology is still in its infancy and experience is still being built up. Most
      studies till now have been performed in the coronary arteries although the
      superficial femoral artery is an equally appealing area of application.
      Bioresorbable scaffolds are made of resorbable polymers or metals with or without
      antiproliferative drug elution. Early experiences in coronary arteries as well as
      in other areas such as the superficial femoral artery (SFA) have shown the
      importance of the material that is used, the design of the device and the
      duration of the absorption process. They suggest that elution of an
      antiproliferative drug might be necessary to obtain clinically acceptable
      results. Although initial results are promising with some of the newer generation
      devices results of larger studies with longer follow-up are eagerly awaited to
      define the precise place of this new technology. This article gives an overview
      of the existing evidence, the available devices, the clinical studies that have
      been performed in different areas and the preliminary results of a large
      multicenter study with a bioresorbable stent in the SFA.

PMID- 23558659
TI  - BRAVISSIMO: 12-month results from a large scale prospective trial.
AB  - The BRAVISSIMO study is a prospective, non-randomized, multi-center, multi
      national, monitored trial, conducted at 12 hospitals in Belgium and 11 hospitals
      in Italy. This manuscript reports the findings up to the 12-month follow-up time
      point for both the TASC A&B cohort and the TASC C&D cohort. The primary endpoint
      of the study is primary patency at 12 months, defined as a target lesion without
      a hemodynamically significant stenosis on Duplex ultrasound (>50%, systolic
      velocity ratio no greater than 2.0) and without target lesion revascularization
      (TLR) within 12 months. Between July 2009 and September 2010, 190 patients with
      TASC A or TASC B aortoiliac lesions and 135 patients with TASC C or TASC D
      aortoiliac lesions were included. The demographic data were comparable for the
      TASC A/B cohort and the TASC C/D cohort. The number of claudicants was
      significantly higher in the TASC A/B cohort, The TASC C/D cohort contains more
      CLI patients. The primary patency rate for the total patient population was
      93.1%. The primary patency rates at 12 months for the TASC A, B, C and D lesions
      were 94.0%, 96.5%, 91.3% and 90.2% respectively. No statistical significant
      difference was shown when comparing these groups. Our findings confirm that
      endovascular therapy, and more specifically primary stenting, is the preferred
      treatment for patients with TASC A, B, C and D aortoiliac lesions. We notice
      similar endovascular results compared to surgery, however without the invasive
      character of surgery.

PMID- 23558660
TI  - Iliofemoral venous stenting extending into the femoral region: initial clinical
      experience with the purpose-designed Zilver Vena stent.
AB  - AIM: The aim of the study was to assess the early clinical experience with the
      Zilver Vena stent in treating patients with iliofemoral venous obstruction at a
      tertiary referral hospital. METHODS: Demographic, procedural, and follow-up data
      of 20 patients (12 women; mean age of 59 +/- 17 years) treated for iliofemoral
      vein obstruction between January 2011 and December 2012 were retrospectively
      reviewed. Most patients presented with acute obstruction (N.=14; 70%), and 10
      patients (50%) had an active malignancy. Patency was established venographically
      at procedure end, and was evaluated with Duplex ultrasound in follow-up. RESULTS:
      Venous obstructions were attributed primarily to extrinsic compression from a
      malignant or other mass in the pelvis (N.=9) and May-Thurner (N.=5). Flow was re
      established through the obstructed venous segment in all patients at procedure
      end. In follow-up, three patients experienced early stent thrombosis (<30 days);
      the clinical patency rate was 85% (17/20 patients). Clinical improvement was
      demonstrated by decreased leg swelling in the remaining 17 patients. CONCLUSION:
      The Zilver Vena stent performed favorably in this challenging patient population;
      these results need to be confirmed in multicenter studies.

PMID- 23558661
TI  - Endovenous 1470 nm laser treatment of the saphenous vein: early report of pain
      assessment.
AB  - AIM: The aim of the paper was to evaluate the rate of postoperative pain by using
      endovenous laser ablation with wave-length of 1470 nm for incompetent saphenous
      veins in our single center experience. METHODS: A non-randomized prospective
      trial was performed. Patients with symptomatic varicose small saphenous vein and
      great saphenous vein were considered suitable for endovenous laser ablation. The
      VenaCure EVLTTM (Angiodynamics, Queensbury, NY) generator was used to provide
      laser energy (1470 nm emission wavelength). Pain was assessed on the 7th days,
      1st months, 3rd months, and 6th months using a visual analog scale rating of 0 cm
      (no pain) to 10 cm (worst imaginable pain). RESULTS: Of the 30 patients who
      eventually underwent endovenous laser ablation, 14 underwent bilateral treatment.
      Totally, 44 treated legs were scored. When questioned by using a visual analog
      scale pain score of 0-10, patients, on average, graded their pain 3.86 +/- 1.04
      at admission, 2.83 +/- 0.91 at 1 week, 1.46 +/- 0.63 at 1 month, 0.63 +/- 0.49 at
      3 months, and 0.07 +/- 0.25 at 6 months. No major complication occurred, and
      there was no deep venous thrombosis or pulmonary embolism nor skin ulceration.
      CONCLUSION: Endovenous laser ablation for chronic venous insufficiency with a
      1470-nm diode laser appears to be effective and safe. The procedure is simple to
      perform, well accepted by patients and relatively atraumatic.

PMID- 23558662
TI  - Arthroscopic management of occult greater tuberosity fracture of the shoulder.
AB  - PURPOSE: The purpose of this retrospective study was to evaluate the early
      results of arthroscopic treatment in patients with missed occult greater
      tuberosity (GT) fracture of the humerus using the arthroscopic suture-bridge
      fixation technique. METHODS: Between January 2007 and August 2010, we used
      arthroscopic suture-bridge fixation in 15 cases of missed occult GT fractures,
      which were referred to our department with persistent symptoms following trauma,
      despite physical therapy. Occult GT fracture was diagnosed with bone marrow edema
      seen on magnetic resonance imaging in all patients. There were 13 male and 2
      female patients with a mean age of 45 years (range 31-67 years). Mean time period
      until the surgery following the initial trauma was 4 months (1.5-12 months). For
      the measurement of clinical outcomes, we assessed the range of motion and
      evaluated the University of California, Los Angeles (UCLA) American Shoulder and
      Elbow Surgeons (ASES) scores and simple shoulder test (SST). RESULTS: The early
      clinical results were evaluated in these patients at a mean of 24 months (range
      14-36 months) after surgery. All the patients were satisfied with the surgery.
      The mean UCLA, ASES, and SST scores improved from preoperative 15, 39, and 2 to
      postoperative 33, 91, and 11, respectively (P < .05). Mean forward flexion,
      abduction, external rotation at the neutral position, and internal rotation were
      improved to 159 degrees , 155 degrees , 24 degrees , and L1, respectively, at the
      final follow-up. CONCLUSION: In the occult GT fracture with persistent shoulder
      symptoms, arthroscopic suture-bridge fixation and early rehabilitation showed
      excellent clinical outcomes on a short-term follow-up study. LEVEL OF EVIDENCE:
      Retrospective review, Level IV.

PMID- 23558663
TI  - Reproducibility of radiographic assessment of femoral implant position after hip
      resurfacing arthroplasty: a pilot study.
AB  - To determine whether femoral implant position can be reproducibly measured on
      plain digital radiographs, we prospectively studied 40 patients after hip
      resurfacing arthroplasty. Three observers performed double blinded randomized
      analysis of calibrated digital radiographs meeting strict quality criteria. The
      implant stem-shaft angle and femoral anteversion angle were measured by the
      trapezoid method of axis determination using OsiriX software. The upper and lower
      offset and the anterior and posterior offset were measured. The statistical
      analysis was performed using Pearson correlation tests (intra-observer
      reproducibility) and Fisher F tests (inter-observer reproducibility). Intra
      observer reproducibility was very good for all parameters and all observers.
      Inter-observer reproducibility was excellent except for superior offset
      measurement. Thus, this study validates a radiographic method for assessing the
      femoral implant position in hip resurfacing. We believe this could be useful for
      future studies on hip resurfacing devices. 

PMID- 23558664
TI  - The relationship between passive stiffness and muscle power output: influence of
      muscle cross-sectional area normalization.
AB  - INTRODUCTION: We examined the relationship between passive stiffness of posterior
      hip and thigh muscles and muscle power output before and after normalization of
      passive stiffness to muscle cross-sectional area (CSA). METHODS: Pearson
      correlation coefficients (r) were used to assess the relationships between the
      normalized and non-normalized slopes of the initial (phase 1) and final (phase 2)
      portions of the angle-torque curve and peak power output (Pmax). RESULTS: A
      significant positive relationship was observed between the non-normalized slope
      of phase 1 and Pmax (r = 0.723; P <= 0.001); however, no correlations were
      observed between the normalized slope of phase 1 and Pmax (r = 0.244; P = 0.299)
      nor between Pmax and the normalized and non-normalized slopes of phase 2 (r = 
      0.159-0.418; P = 0.067-0.504). CONCLUSIONS: The findings suggest that muscle
      size, rather than stiffness, accounted for a significant portion of the variance
      in muscle power output.

PMID- 23558666
TI  - Acute bronchodilator responsiveness to tiotropium in postinfectious bronchiolitis
      obliterans in children.
AB  - BACKGROUND: Patients with postinfectious bronchiolitis obliterans (PIBO) usually
      have severe airflow obstruction and respond poorly to beta-adrenergic drugs.
      However, the bronchodilator response to an anticholinergic agent such as
      tiotropium bromide is not known. We studied the acute bronchodilator response to
      tiotropium for up to 24 h in children with PIBO using spirometric and
      plethysmographic criteria. METHODS: A randomized, double-blind, placebo
      controlled, crossover, prospective study was performed in patients with stable
      PIBO, 6 to 16 years of age. Standard spirometry and plethysmography were
      performed before and at 30, 60, 120, and 180 min and 24 h after inhalation of 18
      MUg of tiotropium or a placebo. After 7 to 14 days, the drugs were inverted, and
      the procedures were repeated. The changes in lung function parameters at each
      time point were compared with the baseline by analysis of variance and Tukey
      posttest, and the differences in all time points assessments vs baseline in
      tiotropium vs placebo groups were compared using the Friedman test. RESULTS: A
      total of 30 patients were enrolled in the study (23 boys, seven girls; aged 10.9
      +/- 2.8 years) with baseline lung function values (% predicted) of FVC, FEV1,
      FEV1/FVC, forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), total
      lung capacity (TLC), residual volume (RV), RV/TLC, airway resistance (Raw), and
      specific airway conductance (sGaw) of 75 +/- 15, 48 +/- 14, 59 +/- 11, 22 +/- 11,
      120 +/- 19, 281 +/- 101, 49 +/- 13, 250 +/- 65, and 23 +/- 9, respectively.
      Statistically significant differences were observed after tiotropium inhalation
      in the following parameters compared with baseline: FVC at 60, 120, and 180 min
      and 24 h; FEV1 at 30, 60, 120, and 180 min; FEV1/FVC at 60, 120, and 180 min;
      FEF25%-75% at 60, 120, and 180 min; RV at 30, 60, 120, and 180 min; TLC at 30,
      120, and 180 min; RV/TLC at 30, 60, 120, and 180 min; Raw at 30, 60, 120, and 180
      min and 24 h; and sGaw at 30, 60, 120, and 180 min and 24 h. For the placebo
      group, no significant differences were observed in any lung function parameters
      at any time. The differences in the main functional measurements between the
      tiotropium and placebo groups were statistically significant. CONCLUSIONS:
      Tiotropium acutely decreased airway obstruction and air trapping for up to 24 h
      in children with PIBO.

PMID- 23558667
TI  - An effective active surveillance method for controlling nosocomial MRSA
      transmission in a Japanese hospital.
AB  - Hospital-wide active surveillance for methicillin-resistant Staphylococcus aureus
      (MRSA) targeted to adult patients with a history of MRSA carriage within the past
      5 years was performed in Juntendo University Hospital (JUH) over a 2-year period.
      In the first year, MRSA screening culture was ordered by physicians in charge. In
      the second year, infection-control practitioners (ICPs) took samples for active
      surveillance culture. The average monthly transmission rate of MRSA in JUH was
      0.35 per 1,000 bed-days in the first year and decreased significantly to 0.26 per
      1,000 bed-days in the second year (P < 0.05). In the second year, more active
      commitment of ICPs to MRSA screening was effective in improving the performance
      rate of screening, shortening turn-around time of screening results, and
      decreasing transmission rate. Increasing compliance with active MRSA surveillance
      by involvement of ICPs, targeting patients with a previous history of MRSA
      carriage in the previous 5 years, was effective to control nosocomial MRSA
      transmission. 

PMID- 23558665
TI  - Age-dependent cost-utility of pediatric cochlear implantation.
AB  - OBJECTIVES: Cochlear implantation (CI) has become the mainstay of treatment for
      children with severe-to-profound sensorineural hearing loss (SNHL). Yet, despite
      mounting evidence of the clinical benefits of early implantation, little data are
      available on the long-term societal benefits and comparative effectiveness of
      this procedure across various ages of implantation-a choice parameter for parents
      and clinicians with high prognostic value for clinical outcome. As such, the aim
      of the present study is to evaluate a model of the consequences of the timing of
      this intervention from a societal economic perspective. Average cost utility of
      pediatric CI by age at intervention will be analyzed. DESIGN: Prospective,
      longitudinal assessment of health utility and educational placement outcomes in
      175 children recruited from six U.S. centers between November 2002 and December
      2004, who had severe-to-profound SNHL onset within 1 year of age, underwent CI
      before 5 years of age, and had up to 6 years of postimplant follow-up that ended
      in November 2008 to December 2011. Costs of care were collected retrospectively
      and stratified by preoperative, operative, and postoperative expenditures.
      Incremental costs and benefits of implantation were compared among the three age
      groups and relative to a nonimplantation baseline. RESULTS: Children implanted at
      <18 months of age gained an average of 10.7 quality-adjusted life years (QALYs)
      over their projected lifetime as compared with 9.0 and 8.4 QALYs for those
      implanted between 18 and 36 months and at >36 months of age, respectively.
      Medical and surgical complication rates were not significantly different among
      the three age groups. In addition, mean lifetime costs of implantation were
      similar among the three groups, at approximately $2000/child/year (77.5-year life
      expectancy), yielding costs of $14,996, $17,849, and $19,173 per QALY for the
      youngest, middle, and oldest implant age groups, respectively. Full mainstream
      classroom integration rate was significantly higher in the youngest group at 81%
      as compared with 57 and 63% for the middle and oldest groups, respectively (p <
      0.05) after 6 years of follow-up. After incorporating lifetime educational cost
      savings, CI led to net societal savings of $31,252, $10,217, and $6,680 for the
      youngest, middle, and oldest groups at CI, respectively, over the child's
      projected lifetime. CONCLUSIONS: Even without considering improvements in
      lifetime earnings, the overall cost-utility results indicate highly favorable
      ratios. Early (<18 months) intervention with CI was associated with greater and
      longer quality-of-life improvements, similar direct costs of implantation, and
      economically valuable improved classroom placement, without a greater incidence
      of medical and surgical complications when compared to CI at older ages.

PMID- 23558669
TI  - Salmonella enhance chemosensitivity in tumor through connexin 43 upregulation.
AB  - The use of preferentially replicating bacteria as oncolytic agents is one of the
      innovative approaches for the treatment of cancer. The capability of Salmonella
      to disperse within tumors and hence to delay tumor growth was augmented when
      combined with chemotherapy. This work is warranted to elucidate the underlying
      mechanism of antitumor effects by the combination therapy of Salmonella and
      cisplatin. The presence of functional gap junctions is highly relevant for the
      success of chemotherapy. Following Salmonella treatment, dose- and time-dependent
      upregulation of connexin 43 (Cx43) expressions were observed. Moreover,
      Salmonella significantly enhanced gap intercellular communication (GJIC), as
      revealed by the fluorescent dye scrape loading assay. To study the pathway
      underlying these Salmonella-induced effects, we found that Salmonella induced a
      significant increase in mitogen-activated protein kinases (MAPK) signaling
      pathways. The Salmonella-induced upregulation of Cx43 was prevented by treatment
      of cells with the phosphorylated p38 inhibitor, but not phosphorylated
      extracellular signal-regulated kinase (pERK) inhibitor or phosphorylated c-jun N
      terminal kinase (pJNK) inhibitor. Specific knockdown of Cx43 had an inhibitory
      effect on GJIC and resulted in a reduction of cell death after Salmonella and
      cisplatin treatment. Our results suggest that accumulation of Salmonella in tumor
      sites leads to increase Cx43 gap junction communication and enhances the
      combination of Salmonella and cisplatin therapeutic effects. 

PMID- 23558671
TI  - Spatial-temporal protein expression of inhibitor of differentiation-1 (Id1)
      during fetal embryogenesis and in different mouse and human cancer types.
AB  - Inhibitor of differentiation-1 (Id1) plays a role in cell proliferation,
      acquisition of epithelial to mesenchymal transition (EMT) features and
      angiogenesis. Id1 was shown to be expressed in some tumor types, mainly in
      advanced dedifferentiated stages. However, recent studies using a validated and
      highly specific monoclonal antibody against Id1 have challenged many of the
      results obtained by immunohistochemistry. The goal of our work was to perform a
      thorough analysis of Id1 expression in mouse embryos and adult tissues, as well
      as healthy and malignant mouse and human samples using this validated antibody
      (Perk et al., 2006). Our results show that Id1 was highly expressed in the
      oropharyngeal cavity, lung, cartilage and skin of E14 and E15 mouse embryos, but
      expression was progressively reduced in more developed embryos. Immunostaining
      only remained in epithelial cells of the gut and uterus of adult mice. Mammary
      MMTV-Myc and MMTV-Myc/VEGF transgenic mouse tumors, and squamous cell carcinomas
      of the lung induced by N-nitroso-tris-chloroethylurea (NTCU) were highly positive
      for Id1, unlike their respective healthy counterparts. Id1 immunostaining in a
      human tissue microarray (TMA) revealed strong expression in cancers of the oral
      cavity, bladder and cervix. Some tumor specimens of esophagus, thyroid and breast
      were also strongly positive. Our results suggest that Id1 is an oncofetal protein
      highly expressed in particular tumor types that should be reanalyzed in future
      studies using large cohorts of patients to reassess its diagnostic/prognostic
      value. Moreover, MMTV-Myc- and NTCU-induced tumors could serve as appropriate
      mouse models to study Id1 functions in breast and lung cancer, respectively.

PMID- 23558670
TI  - The decline of verbal and visuospatial working memory across the adult life span.
AB  - It has been well established that working memory abilities decrease with
      advancing age; however, the specific time point in the adult life span at which
      this deficit begins and the rate at which it advances are still controversial.
      There is no agreement on whether working memory declines equally for visuospatial
      and verbal information, and the literature disagrees on how task difficulty may
      influence this decay. We addressed these questions in a lifespan sample of 1,500
      participants between 21 and 80 years old. The n-back task was used, with letters
      and circles presented at different positions around an imaginary circle, to
      evaluate working memory in the verbal and visuospatial domains, respectively. The
      participants' task was to judge whether the current stimulus matched a stimulus
      that was shown n trials prior. Both domains were evaluated in two levels of
      difficulty: 1-back and 2-back. The comparison across decades showed that
      discrimination in the visuospatial and 1-back tasks started to decline earlier in
      women than in men; however, discrimination was equal between the sexes in the
      verbal and 2-back tasks. Performance on tasks in the visuospatial domain
      exhibited more pronounced decline than in those in the verbal domain. The rate of
      decline in working memory accuracy was superior in 2-back tasks than in 1-back
      tasks, independent of the domain. These results revealed that the effects of
      aging on working memory are less dependent on the type of information and more
      reliant on the resources demanded by the task.

PMID- 23558672
TI  - Emerging roles of TRPA1 in sensation of oxidative stress and its implications in
      defense and danger.
AB  - Transient receptor potential ankyrin subtype 1 (TRPA1) is a well-known ion
      channel that play a central role for pain sensation. In the peripheral sensory
      nerve terminals innervating the body tegument or organs, TRPA1 detects and is
      activated by diverse harmful environmental and internal stimuli. The TRPA1
      activation results in neuronal firing, which finally sends a warning signal to
      our brain. However, sensitization or sustained activation of TRPA1 often causes
      plastic changes both in the neural pathway and in the peripheral tissues, leading
      to a pathologic state in tissue health and pain mediation. Recently, a unique
      covalent detection mode for reactive biological attacks was uncovered in the
      sensory mechanisms of TRPA1. Notably, the pool of the newly found reactive
      stimulators for TRPA1 includes oxidative stress. Here, we overview the nature of
      this interaction, and try to find biological meanings of the participation of
      such a rapid ionotrophic component in disease exacerbations. Acutely, its
      relatively rapid response can be understood in terms of efficiency for avoiding
      harmful milieu as quickly as possible, as implicated in the raison d'etre of the
      pain mechanism. Nonetheless, complex situations in a chronic disease progress may
      occur. As well, multiple interplays with known molecules on the redox defense
      mechanism are anticipated. At a therapeutic angle, how to control TRPA1 for
      promoting body's defensive potential will be a practical question but remains to
      be answered. Future investigations will likely give more detailed insights to
      understand the roles and target validity of TRPA1. 

PMID- 23558673
TI  - Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease
      free survival in advanced gastric cancer.
AB  - PURPOSE: In a retrospective analysis, adjuvant intensity-modulated radiation
      therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer
      survival rates compared to a combination of three-dimensional conformal radiation
      therapy (3D-CRT) and conventional chemotherapy. We report on the long-term
      outcomes of two consecutive patient cohorts that were treated with either IMRT
      and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. PATIENTS AND
      METHODS: Between 2001 and 2008, 65 consecutive gastric cancer patients received
      either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy
      comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier
      cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary
      endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS:
      Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively
      (p = 0.0602). Actuarial 5-year OS rates were 26 and 47  %, respectively. Within
      the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this
      difference was not statistically significant. The primary cause of death in both
      groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D
      CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were
      22 and 44  %, respectively. Among patients receiving 5-FU/FA, DFS tended to be
      better in the IMRT group, but this was not statistically significant. A similar
      analysis for the XELOX group was not possible as 3D-CRT was almost never used to
      treat these patients. No late toxicity exceeding grade 3 or secondary tumors were
      observed. CONCLUSION: After a median follow-up period of over 5 years, OS and DFS
      were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA
      group. Long-term observation revealed no clinical indications of therapy-induced
      secondary tumors or renal toxicity.

PMID- 23558674
TI  - Response-adaptive decision-theoretic trial design: operating characteristics and
      ethics.
AB  - Adaptive randomization is used in clinical trials to increase statistical
      efficiency. In addition, some clinicians and researchers believe that using
      adaptive randomization leads necessarily to more ethical treatment of subjects in
      a trial. We develop Bayesian, decision-theoretic, clinical trial designs with
      response-adaptive randomization and a primary goal of estimating treatment effect
      and then contrast these designs with designs that also include in their loss
      function a cost for poor subject outcome. When the loss function did not
      incorporate a cost for poor subject outcome, the gains in efficiency from
      response-adaptive randomization were accompanied by ethically concerning subject
      allocations. Conversely, including a cost for poor subject outcome demonstrated a
      more acceptable balance between the competing needs in the trial. A subsequent,
      parallel set of trials designed to control explicitly types I and II error rates
      showed that much of the improvement achieved through modification of the loss
      function was essentially negated. Therefore, gains in efficiency from the use of
      a decision-theoretic, response-adaptive design using adaptive randomization may
      only be assumed to apply to those goals that are explicitly included in the loss
      function. Trial goals, including ethical ones, which do not appear in the loss
      function, are ignored and may even be compromised; it is thus inappropriate to
      assume that all adaptive trials are necessarily more ethical. Controlling types I
      and II error rates largely negates the benefit of including competing needs in
      favor of the goal of parameter estimation.

PMID- 23558675
TI  - Treatment strategies for aortic and peripheral prosthetic graft infection.
AB  - PURPOSE: The aim of this study was to investigate the outcomes correlated with
      our treatment strategy for prosthetic graft infection. METHODS: Seventeen
      patients were treated for prosthetic graft infections between 1997 and 2009.
      Initially, total graft excision was applied in five cases, partial graft excision
      was applied in six cases and graft preservation with drainage and irrigation was
      applied in six cases. Among the graft-preserved cases, four patients were
      infected with methicillin-resistant Staphylococcus aureus (MRSA) and treated with
      gentian violet (GV). RESULTS: The overall survival rate was 88% at 30 days and
      82% at 1 year in this series. Of the excised cases, nine patients survived;
      however, two patients died. Among the cases in which MRSA-infected grafts were
      preserved, three patients survived; however, one patient died under a septicemic
      state. Infected graft preservation was applied at a high rate of 36%, and the
      mortality rate remained at 16%, without any signs of graft reinfection.
      CONCLUSIONS: In the treatment of infected grafts, the patient's condition should
      be considered in order to select the appropriate treatment in each case. Graft
      preservation should be considered as an alternative treatment option, especially
      in high-risk patients, and GV can be effective for conservative treatment of
      prosthetic graft infections, including MRSA infections.

PMID- 23558676
TI  - Limited sampling strategy for the estimation of mycophenolic acid area under the
      concentration-time curve treated in Japanese living-related renal transplant
      recipients with concomitant extended-release tacrolimus.
AB  - Mycophenolate mofetil (MMF) is used for oral administration to prevent rejection
      in renal transplant recipients, and is rapidly converted into mycophenolic acid
      (MPA), the active metabolite, by hydrolysis in vivo. The area under the
      concentration-time curve (AUC(0-12 h)) of MPA is considered to be an effective
      pharmacokinetics parameter for predicting acute rejection. However, frequent
      blood sampling is required to calculate AUC(0-12 h), which imposes a burden on
      patients and providers. Therefore, we examined a limited sampling strategy (LSS)
      for estimation of MPA-AUC(0-12 h) using only a trough level (C0) and two points
      including C0 in Japanese living-related renal transplant recipients with
      concomitant extended-release tacrolimus (ER-TAC). The present study suggests that
      better estimation of MPA-AUC(0-12 h) can be obtained by using two points
      including C0 as compared with only C0 regardless of transplant progress.
      Furthermore, blood collection points showing the highest estimation of MPA-AUC(0
      12 h) by adding to C0 were C4 at pre-transplantation (Tx) and 1 month post-Tx,
      and C6 at 3 months post-Tx. We conjecture that changes in renal function and
      serum albumin (Alb) accompanying transplant progress are aggravating factors in
      terms of estimation, because there was also a significant difference in the
      reciprocal of serum creatinine (1/Scr) and Alb between pre-Tx and post-Tx in this
      study. In conclusion, the present study provides useful information for effective
      and efficient monitoring of MPA levels in Japanese living-related renal
      transplant recipients.

PMID- 23558677
TI  - Abelson interactor 1 (ABI1) and its interaction with Wiskott-Aldrich syndrome
      protein (wasp) are critical for proper eye formation in Xenopus embryos.
AB  - Abl interactor 1 (Abi1) is a scaffold protein that plays a central role in the
      regulation of actin cytoskeleton dynamics as a constituent of several key protein
      complexes, and homozygous loss of this protein leads to embryonic lethality in
      mice. Because this scaffold protein has been shown in cultured cells to be a
      critical component of pathways controlling cell migration and actin regulation at
      cell-cell contacts, we were interested to investigate the in vivo role of Abi1 in
      morphogenesis during the development of Xenopus embryos. Using morpholino
      mediated translation inhibition, we demonstrate that knockdown of Abi1 in the
      whole embryo, or specifically in eye field progenitor cells, leads to disruption
      of eye morphogenesis. Moreover, signaling through the Src homology 3 domain of
      Abi1 is critical for proper movement of retinal progenitor cells into the eye
      field and their appropriate differentiation, and this process is dependent upon
      an interaction with the nucleation-promoting factor Wasp (Wiskott-Aldrich
      syndrome protein). Collectively, our data demonstrate that the Abi1 scaffold
      protein is an essential regulator of cell movement processes required for normal
      eye development in Xenopus embryos and specifically requires an Src homology 3
      domain-dependent interaction with Wasp to regulate this complex morphogenetic
      process.

PMID- 23558678
TI  - Annexin A2 regulates beta1 integrin internalization and intestinal epithelial
      cell migration.
AB  - The gastrointestinal epithelium functions as an important barrier that separates
      luminal contents from the underlying tissue compartment and is vital in
      maintaining mucosal homeostasis. Mucosal wounds in inflammatory disorders
      compromise the critical epithelial barrier. In response to injury, intestinal
      epithelial cells (IECs) rapidly migrate to reseal wounds. We have previously
      observed that a membrane-associated, actin binding protein, annexin A2 (AnxA2),
      is up-regulated in migrating IECs and plays an important role in promoting wound
      closure. To identify the mechanisms by which AnxA2 promotes IEC movement and
      wound closure, we used a loss of function approach. AnxA2-specific shRNA was
      utilized to generate IECs with stable down-regulation of AnxA2. Loss of AnxA2
      inhibited IEC migration while promoting enhanced cell-matrix adhesion. These
      functional effects were associated with increased levels of beta1 integrin
      protein, which is reported to play an important role in mediating the cell-matrix
      adhesive properties of epithelial cells. Because cell migration requires dynamic
      turnover of integrin-based adhesions, we tested whether AnxA2 modulates
      internalization of cell surface beta1 integrin required for forward cell
      movement. Indeed, pulse-chase biotinylation experiments in IECs lacking AnxA2
      demonstrated a significant increase in cell surface beta1 integrin that was
      accompanied by decreased beta1 integrin internalization and degradation. These
      findings support an important role of AnxA2 in controlling dynamics of beta1
      integrin at the cell surface that in turn is required for the active turnover of
      cell-matrix associations, cell migration, and wound closure.

PMID- 23558679
TI  - Drosophila homologues of adenomatous polyposis coli (APC) and the formin
      diaphanous collaborate by a conserved mechanism to stimulate actin filament
      assembly.
AB  - BACKGROUND: Vertebrate APC collaborates with Dia through its Basic domain to
      assemble actin filaments. RESULTS: Despite limited sequence homology between the
      vertebrate and Drosophila APC Basic domains, Drosophila APC1 collaborates with
      Dia to stimulate actin assembly in vitro. CONCLUSION: The mechanism of actin
      assembly is highly conserved over evolution. SIGNIFICANCE: APC-Dia collaborations
      may be crucial in a wide range of animal cells. Adenomatous polyposis coli (APC)
      is a large multidomain protein that regulates the cytoskeleton. Recently, it was
      shown that vertebrate APC through its Basic domain directly collaborates with the
      formin mDia1 to stimulate actin filament assembly in the presence of nucleation
      barriers. However, it has been unclear whether these activities extend to
      homologues of APC and Dia in other organisms. Drosophila APC and Dia are each
      required to promote actin furrow formation in the syncytial embryo, suggesting a
      potential collaboration in actin assembly, but low sequence homology between the
      Basic domains of Drosophila and vertebrate APC has left their functional and
      mechanistic parallels uncertain. To address this question, we purified Drosophila
      APC1 and Dia and determined their individual and combined effects on actin
      assembly using both bulk fluorescence assays and total internal reflection
      fluorescence microscopy. Our data show that APC1, similar to its vertebrate
      homologue, bound to actin monomers and nucleated and bundled filaments. Further,
      Drosophila Dia nucleated actin assembly and protected growing filament barbed
      ends from capping protein. Drosophila APC1 and Dia directly interacted and
      collaborated to promote actin assembly in the combined presence of profilin and
      capping protein. Thus, despite limited sequence homology, Drosophila and
      vertebrate APCs exhibit highly related activities and mechanisms and directly
      collaborate with formins. These results suggest that APC-Dia interactions in
      actin assembly are conserved and may underlie important in vivo functions in a
      broad range of animal phyla.

PMID- 23558680
TI  - Interactions between NF-kappaB and SP3 connect inflammatory signaling with
      reduced FGF-10 expression.
AB  - Inflammation inhibits normal lung morphogenesis in preterm infants. Soluble
      inflammatory mediators present in the lungs of patients developing
      bronchopulmonary dysplasia disrupt expression of multiple genes critical for
      development. However, the mechanisms linking innate immune signaling and
      developmental programs are not clear. NF-kappaB activation inhibits expression of
      the critical morphogen FGF-10. Here, we show that interactions between the RELA
      subunit of NF-kappaB and SP3 suppress SP1-mediated FGF-10 expression. SP3 co
      expression reduced SP1-mediated Fgf-10 promoter activity, suggesting antagonistic
      interactions between SP1 and SP3. Chromatin immunoprecipitation of LPS-treated
      primary mouse fetal lung mesenchymal cells detected increased interactions
      between SP3, RELA, and the Fgf-10 promoter. Expression of a constitutively active
      IkappaB kinase beta mutant not only decreased Fgf-10 promoter activity but also
      increased RELA-SP3 nuclear interactions. Expression of a dominant-negative
      IkappaB, which blocks NF-kappaB nuclear translocation, prevented inhibition of
      FGF-10 by SP3. The inhibitory functions of SP3 required sequences located in the
      N-terminal region of the protein. These data suggested that inhibition of FGF-10
      by inflammatory signaling involves the NF-kappaB-dependent interactions between
      RELA, SP3, and the Fgf-10 promoter. NF-kappaB activation may therefore lead to
      reduced gene expression by recruiting inhibitory factors to specific gene
      promoters following exposure to inflammatory stimuli.

PMID- 23558681
TI  - Structural and biochemical analyses of glycoside hydrolase families 5 and 26 beta
      (1,4)-mannanases from Podospora anserina reveal differences upon manno
      oligosaccharide catalysis.
AB  - The microbial deconstruction of the plant cell wall is a key biological process
      that is of increasing importance with the development of a sustainable biofuel
      industry. The glycoside hydrolase families GH5 (PaMan5A) and GH26 (PaMan26A) endo
      beta-1,4-mannanases from the coprophilic ascomycete Podospora anserina contribute
      to the enzymatic degradation of lignocellulosic biomass. In this study, P.
      anserina mannanases were further subjected to detailed comparative analysis of
      their substrate specificities, active site organization, and transglycosylation
      capacity. Although PaMan5A displays a classical mode of action, PaMan26A revealed
      an atypical hydrolysis pattern with the release of mannotetraose and mannose from
      mannopentaose resulting from a predominant binding mode involving the -4 subsite.
      The crystal structures of PaMan5A and PaMan26A were solved at 1.4 and 2.85 A
      resolution, respectively. Analysis of the PaMan26A structure supported strong
      interaction with substrate at the -4 subsite mediated by two aromatic residues
      Trp-244 and Trp-245. The PaMan26A structure appended to its family 35
      carbohydrate binding module revealed a short and proline-rich rigid linker that
      anchored together the catalytic and the binding modules.

PMID- 23558682
TI  - Porphyromonas gingivalis virulence factor gingipain RgpB shows a unique zymogenic
      mechanism for cysteine peptidases.
AB  - Zymogenicity is a regulatory mechanism that prevents inadequate catalytic
      activity in the wrong context. It plays a central role in maintaining microbial
      virulence factors in an inactive form inside the pathogen until secretion. Among
      these virulence factors is the cysteine peptidase gingipain B (RgpB), which is
      the major virulence factor secreted by the periodontopathogen Porphyromonas
      gingivalis that attacks host vasculature and defense proteins. The structure of
      the complex between soluble mature RgpB, consisting of a catalytic domain and an
      immunoglobulin superfamily domain, and its 205-residue N-terminal prodomain, the
      largest structurally characterized to date for a cysteine peptidase, reveals a
      novel fold for the prodomain that is distantly related to sugar-binding lectins.
      It attaches laterally to the catalytic domain through a large concave surface.
      The main determinant for latency is a surface "inhibitory loop," which approaches
      the active-site cleft of the enzyme on its non-primed side in a substrate-like
      manner. It inserts an arginine (Arg(126)) into the S1 pocket, thus matching the
      substrate specificity of the enzyme. Downstream of Arg(126), the polypeptide
      leaves the cleft, thereby preventing cleavage. Moreover, the carbonyl group of
      Arg(126) establishes a very strong hydrogen bond with the co-catalytic histidine,
      His(440), pulling it away from the catalytic cysteine, Cys(473), and toward
      Glu(381), which probably plays a role in orienting the side chain of His(440)
      during catalysis. The present results provide the structural determinants of
      zymogenic inhibition of RgpB by way of a novel inhibitory mechanism for
      peptidases in general and open the field for the design of novel inhibitory
      strategies in the treatment of human periodontal disease.

PMID- 23558683
TI  - Alternative pyrimidine biosynthesis protein ApbE is a flavin transferase
      catalyzing covalent attachment of FMN to a threonine residue in bacterial
      flavoproteins.
AB  - Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) contains two flavin
      residues as redox-active prosthetic groups attached by a phosphoester bond to
      threonine residues in subunits NqrB and NqrC. We demonstrate here that
      flavinylation of truncated Vibrio harveyi NqrC at Thr-229 in Escherichia coli
      cells requires the presence of a co-expressed Vibrio apbE gene. The apbE genes
      cluster with genes for Na(+)-NQR and other FMN-binding flavoproteins in bacterial
      genomes and encode proteins with previously unknown function. Experiments with
      isolated NqrC and ApbE proteins confirmed that ApbE is the only protein factor
      required for NqrC flavinylation and also indicated that the reaction is Mg(2+)
      dependent and proceeds with FAD but not FMN. Inactivation of the apbE gene in
      Klebsiella pneumoniae, wherein the nqr operon and apbE are well separated in the
      chromosome, resulted in a complete loss of the quinone reductase activity of
      Na(+)-NQR, consistent with its dependence on covalently bound flavin. Our data
      thus identify ApbE as a novel modifying enzyme, flavin transferase.

PMID- 23558684
TI  - Aberrant assembly of RNA recognition motif 1 links to pathogenic conversion of
      TAR DNA-binding protein of 43 kDa (TDP-43).
AB  - Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological
      signature of amyotrophic lateral sclerosis (ALS). Although accumulating evidence
      suggests the involvement of RNA recognition motifs (RRMs) in TDP-43
      proteinopathy, it remains unclear how native TDP-43 is converted to pathogenic
      forms. To elucidate the role of homeostasis of RRM1 structure in ALS
      pathogenesis, conformations of RRM1 under high pressure were monitored by NMR. We
      first found that RRM1 was prone to aggregation and had three regions showing
      stable chemical shifts during misfolding. Moreover, mass spectrometric analysis
      of aggregated RRM1 revealed that one of the regions was located on protease
      resistant beta-strands containing two cysteines (Cys-173 and Cys-175), indicating
      that this region served as a core assembly interface in RRM1 aggregation.
      Although a fraction of RRM1 aggregates comprised disulfide-bonded oligomers, the
      substitution of cysteine(s) to serine(s) (C/S) resulted in unexpected
      acceleration of amyloid fibrils of RRM1 and disulfide-independent aggregate
      formation of full-length TDP-43. Notably, TDP-43 aggregates with RRM1-C/S
      required the C terminus, and replicated cytopathologies of ALS, including
      mislocalization, impaired RNA splicing, ubiquitination, phosphorylation, and
      motor neuron toxicity. Furthermore, RRM1-C/S accentuated inclusions of familial
      ALS-linked TDP-43 mutants in the C terminus. The relevance of RRM1-C/S-induced
      TDP-43 aggregates in ALS pathogenesis was verified by immunolabeling of
      inclusions of ALS patients and cultured cells overexpressing the RRM1-C/S TDP-43
      with antibody targeting misfolding-relevant regions. Our results indicate that
      cysteines in RRM1 crucially govern the conformation of TDP-43, and aberrant self
      assembly of RRM1 at amyloidogenic regions contributes to pathogenic conversion of
      TDP-43 in ALS.

PMID- 23558685
TI  - Dysferlin regulates cell adhesion in human monocytes.
AB  - Dysferlin is mutated in a group of muscular dystrophies commonly referred to as
      dysferlinopathies. It is highly expressed in skeletal muscle, where it is
      important for sarcolemmal maintenance. Recent studies show that dysferlin is also
      expressed in monocytes. Moreover, muscle of dysferlinopathy patients is
      characterized by massive immune cell infiltrates, and dysferlin-negative
      monocytes were shown to be more aggressive and phagocytose more particles. This
      suggests that dysferlin deregulation in monocytes might contribute to disease
      progression, but the molecular mechanism is unclear. Here we show that dysferlin
      expression is increased with differentiation in human monocytes and the THP1
      monocyte cell model. Freshly isolated monocytes of dysferlinopathy patients show
      deregulated expression of fibronectin and fibronectin-binding integrins, which is
      recapitulated by transient knockdown of dysferlin in THP1 cells. Dysferlin forms
      a protein complex with these integrins at the cell membrane, and its depletion
      impairs cell adhesion. Moreover, patient macrophages show altered adhesion and
      motility. These findings suggest that dysferlin is involved in regulating
      cellular interactions and provide new insight into dysferlin function in
      inflammatory cells.

PMID- 23558686
TI  - Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and
      TIF2-associated modulatory protein gene) in male mice causes sperm malformation
      and infertility.
AB  - TTLL5/STAMP (tubulin tyrosine ligase-like family member 5) has multiple
      activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity,
      augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid
      receptor-regulated gene induction and repression, and displays steroid
      independent growth activity with several cell types. To examine TTLL5/STAMP
      functions in whole animals, mice were prepared with an internal deletion that
      eliminated several activities of the Stamp gene. This mutation causes both
      reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein.
      Homozygous targeted mutant (Stamp(tm/tm)) mice appear normal except for marked
      decreases in male fertility associated with defects in progressive sperm
      motility. Abnormal axonemal structures with loss of tubulin doublets occur in
      most Stamp(tm/tm) sperm tails in conjunction with substantial reduction in alpha
      tubulin polyglutamylation, which closely correlates with the reduction in mutant
      STAMP mRNA. The axonemes in other structures appear unaffected. There is no
      obvious change in the organs for sperm development of WT versus Stamp(tm/tm)
      males despite the levels of WT STAMP mRNA in testes being 20-fold higher than in
      any other organ examined. This defect in male fertility is unrelated to other
      Ttll genes or 24 genes previously identified as important for sperm function.
      Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated
      pathway for alpha-tubulin polyglutamylation that is required for sperm maturation
      and motility and may be relevant for male fertility.

PMID- 23558687
TI  - Comment on Afshar-Oromieh et al.: PET imaging with a [68Ga]gallium-labelled PSMA
      ligand for the diagnosis of prostate cancer: biodistribution in humans and first
      evaluation of tumour lesions.

PMID- 23558688
TI  - Reply to Reske et al.: PET imaging with a [68Ga]gallium-labelled PSMA ligand for
      the diagnosis of prostate cancer: biodistribution in humans and first evaluation
      of tumour lesions.

PMID- 23558689
TI  - Diagnostic accuracy of 18F-FDG PET/CT for detecting recurrence in patients with
      primary skeletal Ewing sarcoma.
AB  - PURPOSE: To evaluate the diagnostic accuracy of (18)F-FDG PET/CT for detecting
      recurrence in patients with primary skeletal Ewing sarcoma. METHODS: We
      retrospectively analysed data from 53 patients (age 20.1 +/- 10.5 years, 39 male)
      who had undergone 71 (18)F-FDG PET/CT studies for suspected recurrence (52
      studies) or for routine follow-up (19 studies) after primary therapy of skeletal
      Ewing sarcoma. (18)F-FDG PET/CT studies were evaluated qualitatively and
      quantitatively (maximum standardized uptake value, SUVmax) by two nuclear
      medicine physicians in consensus. Sensitivity, specificity, predictive values and
      accuracy were calculated on per study basis. Clinical/imaging follow-up (minimum
      6 months) and/or histopathology (when available) were taken as the reference
      standard. RESULTS: Of the total of 71 (18)F-FDG PET/CT studies, 42 (59.1%) were
      positive for recurrence and 29 (40.9%) were negative for recurrence. Local
      recurrence was most common (38 studies) followed by bone metastasis (9 studies),
      and node and lung metastasis (2 studies each). Of the 71 studies, 38 were true
      positive, 27 were true-negative, 4 were false-positive and 2 were false-negative.
      Overall per study based sensitivity was 95%, specificity was 87%, PPV was 90%,
      NPV was 93% and accuracy was 91.5%. No significant difference was found in the
      accuracy of PET/CT between the suspected recurrence group and the routine follow
      up group (94% vs. 84%; P = 0.390). Overall mean lesion SUVmax was 7.8 +/- 4.1
      (range 1.9-17.2). No site-based difference was found in SUVmax. CONCLUSION: (18)F
      FDG PET/CT demonstrates high diagnostic accuracy for detecting recurrence in
      patients with primary skeletal Ewing sarcoma, when it is suspected (clinically or
      on imaging) or during routine follow-up.

PMID- 23558690
TI  - Synthesis of functionalised 4H-quinolizin-4-ones via tandem Horner-Wadsworth
      Emmons olefination/cyclisation.
AB  - 4H-Quinolizin-4-ones are a unique class of heterocycle with valuable
      physicochemical properties and which are emerging as key pharmacophores for a
      range of biological targets. A tandem Horner-Wadsworth-Emmons
      olefination/cyclisation method has been developed to allow facile access to
      substituted 4H-quinolizin-4-ones encoded with a range of functional groups.

PMID- 23558691
TI  - Novel GNE compound heterozygous mutations in a GNE myopathy patient.
AB  - INTRODUCTION: Molecular studies have revealed that some patients with myopathies
      with rimmed vacuoles have pathogenic mutations in the UDP-N-acetylglucosamine-2
      epimerase/N-acetylmannosamine kinase (GNE) and Z-band alternatively spliced PDZ
      motif-containing protein (ZASP) genes. METHODS: We investigated a patient with
      distal myopathy with rimmed vacuoles by muscle biopsy and sequenced 6 candidate
      genes. RESULTS: The patient carried GNE compound heterozygous missense mutations
      (p.V421A and p.N635K) and a ZASP variant (p.D673N). This patient also presented
      with distal weakness sparing the quadriceps muscles and had atypical results for
      Z-band-associated protein immunostaining. This finding indicates that the GNE
      mutations are pathogenic, and the diagnosis is compatible with GNE myopathy.
      CONCLUSIONS: By combining pathological studies and candidate gene screening, we
      identified a patient with GNE myopathy due to novel GNE compound heterozygous
      mutations.

PMID- 23558692
TI  - Anabolic resistance of muscle protein synthesis with aging.
AB  - Aging has been associated with a reduced muscle protein synthetic response to
      protein intake, termed "anabolic resistance." Physical activity performed before
      protein intake increases the use of protein-derived amino acids for postprandial
      muscle protein accretion in senescent muscle. Thus, the level of habitual
      physical activity may be fundamental to maintain the anabolic responsiveness to
      protein intake with aging. 

PMID- 23558693
TI  - How small-sided and conditioned games enhance acquisition of movement and
      decision-making skills.
AB  - This article summarizes research from an ecological dynamics program of work on
      team sports exemplifying how small-sided and conditioned games (SSCG) can enhance
      skill acquisition and decision-making processes during training. The data
      highlighted show how constraints of different SSCG can facilitate emergence of
      continuous interpersonal coordination tendencies during practice to benefit team
      game players. 

PMID- 23558694
TI  - Reduced work capacity in individuals with Down syndrome: a consequence of
      autonomic dysfunction?
AB  - Low work capacity and VO2peak commonly are described phenomena in Down syndrome.
      This is accompanied by chronotropic incompetence and a high incidence of obesity.
      Although many causes of low work capacity in Down syndrome have been proposed,
      little scientific support exists. Our working hypothesis is that autonomic
      dysfunction is the major contributor to the low levels of work capacity in this
      population. 

PMID- 23558695
TI  - The role of Nrf2 in the attenuation of cardiovascular disease.
AB  - Oxidative stress is a component of many human diseases, including cardiovascular
      diseases (CVD). Exercise and various phytochemicals activate nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2), the master regulator of antioxidant
      defenses, and attenuate CVD. This review highlights Nrf2 regulation by exercise
      and phytochemicals and the role of Nrf2 as a therapeutic target in CVD. 

PMID- 23558696
TI  - Chelating ionic liquids for reversible zinc electrochemistry.
AB  - Advanced, high energy-density, metal-air rechargeable batteries, such as zinc
      air, are of intense international interest due to their important role in energy
      storage applications such as electric and hybrid vehicles, and to their ability
      to deal with the intermittency of renewable energy sources such as solar and
      wind. Ionic liquids offer a number of ideal thermal and physical properties as
      potential electrolytes in such large-scale energy storage applications. We
      describe here the synthesis and characterisation of a family of novel "chelating"
      ILs designed to chelate and solubilize the zinc ions to create electrolytes for
      this type of battery. These are based on quaternary alkoxy alkyl ammonium cations
      of varying oligo-ether side chains and anions such as p-toluene sulfonate,
      bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that
      increasing the ether chain length in the cation from two to four oxygens can
      increase the ionic conductivity and reduce the melting point from 67  degrees C
      to 15  degrees C for the tosylate system. Changing the anion also plays a
      significant role in the nature of the zinc deposition electrochemistry. We show
      that zinc can be reversibly deposited from [N(222(20201))][NTf2] and
      [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively,
      but not in the case of tosylate based ILs. This indicates that the [NTf2] is a
      weaker coordinating anion with the zinc cation, compared to the tosylate anion,
      allowing the coordination of the ether chain to dominate the behavior of the
      deposition and stripping of zinc ions.

PMID- 23558697
TI  - Beneficial effects of cardiac rehabilitation in patients with incomplete
      revascularization after primary coronary angioplasty.
AB  - BACKGROUND: There are no reliable data concerning the safety and benefits of
      physical rehabilitation in patients with a two-vessel disease before the second
      stage of angioplasty. The aim of this study was to evaluate the efficiency of
      early cardiac rehabilitation in patients with acute coronary syndromes and with
      angiographically significant residual coronary artery stenosis after a successful
      percutaneous coronary intervention (PCI) into the culprit lesion. DESIGN:
      Retrospective analysis of the results of coronary angiograms and exercise tests
      of patients who underwent stationary rehabilitation after their first ACS and
      first PCI. SETTING: Cardiac Rehabilitation Department. POPULATION: One hundred
      ninety patients divided into 2 groups according to the completeness of myocardial
      revascularization; 49 with significant (>=70%) coronary artery stenosis in a non
      culprit vessel, the mean diameter reduction 80+/-9%; and 141 without any residual
      stenosis. The prevalence of classical risk factors was comparable in both groups.
      Rehabilitation was conducted as a stationary 3-week program. METHODS: Comparison
      of the initial and final exercise test workload in both groups, as well as the
      frequency of adverse effects during the program. RESULTS: Physical training in
      patients with incomplete revascularization (IR) was safe and well tolerated.
      Significant increase of workload capacity after the rehabilitation program was
      observed in both groups: in the IR group from 7.3+/-3.0 to 8.8+/-2.9 MET
      (P<0.0001) and in the complete revascularization (CR) group - from 7.6+/-2.8 to
      9.2+/-2.9 MET (P<0.0001). No significant difference was observed in initial
      workload capacities (P=0.9813) nor in final workload capacities (P=0.8571)
      between the two groups. Two patients in the group with residual lesion (4%) and
      one in the group without residual lesion (0.7%) required urgent PCI during the
      rehabilitation program, P=0.1637. CONCLUSION: Early postinfarction physical
      training is safe and efficient for patients after complete revascularization and
      for those with untreated non-culprit coronary artery stenosis. Gradual increase
      in physical training intensity under cardiologist supervision is essential in
      identifying those rare patients for whom the second stage of angioplasty should
      not be delayed. CLINICAL REHABILITATION IMPACT: Our study shows that patients
      with incomplete revascularization may be qualified for cardiac rehabilitation
      programs.

PMID- 23558698
TI  - Traumatic brain injury shows better functional recovery than brain tumor: a
      rehabilitative perspective.
AB  - BACKGROUND: The similar symptoms seen in the brain tumor (BT) and traumatic brain
      injury (TBI) population. However, functional comparisons between these two
      diagnostic groups have been limited. AIM: To compare functional outcomes in
      patients with supratentorial BT and TBI after early rehabilitation. DESIGN: This
      was a retrospective database analysis. Setting. Patients admitted to an Acute
      Care Unit as inpatient (Hacettepe Hospital, Ankara-Turkey). Population. The
      population included patients with BT and TBI. METHODS: Thirty-four patients with
      BT and TBI were matched one-to-one by lesion side and sex. The Barthel Index was
      used to assess functional status at the pre- and postrehabilitation. The change
      rate and efficiency in BI were also calculated. The time between injury onset and
      admission to rehabilitation (the onset to admission interval, OAI) and length of
      stay in rehabilitation (LOS rehab) were recorded. In addition, the influence of
      lesion side (left and right) and age on functional outcome were analyzed.
      RESULTS: The functional level was significantly lower in TBI patients than in
      patients BT before rehabilitation (P<0.05). The post-rehabilitation BI score was
      similar in patients with BT and TBI (P>0.05). Patients with TBI had greater the
      change rate and efficiency in BI (P<0.05). The OAI and LOS rehab was longer in
      patients with TBI (P<0.05). In terms of lesion side comparisons, no differences
      were found (P>0.05). The age had no effect on functional outcome in patients with
      TBI and BT (P>0.05), expect the age group 45-59 (P<0.05). CONCLUSION: The early
      rehabilitation program improved functional ability of patients with brain tumors,
      as well as patients with traumatic brain injury. Despite the lower functional
      status, patients with TBI displayed better functional recovery than patients with
      BT. Lesion side had no effect on functional outcome in patients with TBI and BT.
      Differences in functional status begin to appear even in patients with TBI
      between 45 and 59 years. Further investigations with more detailed outcome
      instruments are required to better understand the qualitative limitations of a
      patient's recovery. CLINICAL REHABILITATION IMPACT: Patients with TBI will make
      functional gains comparable with patients with brain tumors in a similar
      rehabilitation setting.

PMID- 23558699
TI  - A systematic review of the effectiveness of Kinesio Taping--fact or fashion?
AB  - In this systematic review article, we assessed the effects of therapeutic Kinesio
      Taping (KT) on pain and disability in participants suffering from
      musculoskeletal, neurological and lymphatic pathologies. Four online databases
      (CINAHL, Cochrane Library, MEDLINE, PEDro) were comprehensively searched from
      their inception through March 2012. The initial literature search found 91
      controlled trials. Following elimination procedures, 26 studies were fully
      screened. Subsequently, 12 met our inclusion criteria. The final 12 articles were
      subdivided according to the basic pathological disorders of the participants'
      musculoskeletal (N.=9), neurological (N.=1) and lymphatic (N.=2) systems. As to
      the effect on musculoskeletal disorders, moderate evidence was found supporting
      an immediate reduction in pain while wearing the KT. In 3 out of 6 studies,
      reduction of pain was superior to that of the comparison group. However, there is
      no support indicating any long-term effect. Additionally, no evidence was found
      connecting the KT application to elevated muscle strength or long-term improved
      range of movement. No evidence to support the effectiveness of KT for
      neurological conditions. As to lymphatic disorders, inconclusive evidence was
      reported. Although KT has been shown to be effective in aiding short-term pain,
      there is no firm evidence-based conclusion of the effectiveness of this
      application on the majority of movement disorders within a wide range of
      pathologic disabilities. More research is clearly needed.

PMID- 23558700
TI  - The Italian National Registry of severe acquired brain injury: epidemiological,
      clinical and functional data of 1469 patients.
AB  - BACKGROUND: The lack of knowledge about epidemiological and clinical data of
      patients with Acquired Brain Injury (ABI) admitted to Rehabilitation facilities
      in Italy led to the creation, in June 2008, of a data collection on-line
      registry. AIM: To collect epidemiological and clinical data and to evaluate
      functional outcome of patients with severe traumatic and non-traumatic ABI
      admitted to Rehabilitation facilities in Italy between June 2008 and December
      2011 and to compare data of patients with ABI of different aetiologies. DESIGN:
      Observational retrospective study. SETTING: The study involved 29 Italian
      Rehabilitation facilities. POPULATION: The study enrolled 1469 patients with
      severe traumatic (TBI) and non-traumatic ABI (NTBI). METHODS: Data collected
      included demographic (number of patients with TBI and NTBI, gender, age) and
      clinical characteristics (provenience, number of days elapsed between onset and
      rehabilitation admission, rehabilitation length of stay, discharge destination,
      death and vegetative state diagnosis, presence of percutaneous endoscopic
      gastrostomy, tracheostomy, pressure sores and paraosteoarthropathies). Functional
      outcome was evaluated using the Disability Rating Scale. RESULTS: Of the whole
      population studied, 44.31% and 55.69% patients had suffered a TBI and a NTBI,
      respectively. In the NTBI group 40.09% had a cerebrovascular injury, 12.04% an
      anoxic brain damage, 3.6% had a brain injury of other causes. The mean age was
      43.67 and 56.68 for subjects with TBI and NTBI, respectively. Patients with TBI
      showed a lower onset-admission interval (OAI), compared with NTBI group; no
      difference in rehabilitation length of stay (LOS) was recorded between groups.
      Patients with TBI presented a lower DRS score at admission and discharge and
      returned home more frequently than NTBI group. CONCLUSIONS: The creation of a
      National registry allows the collection of data about patients with ABI in order
      to study the clinical course, the functional outcome and to establish a basis for
      comparison with other data sources. Clinical Rehabilitation Impact. Data
      collection could be useful in the evaluation and planning of rehabilitation
      pathways, and to assess the allocation of healthcare and rehabilitative
      resources.

PMID- 23558701
TI  - The effects of experience on the energy cost of wheelchair propulsion.
AB  - BACKGROUND: Gross mechanical efficiency (GE) of experienced wheelchair users is
      significantly higher than novice able-bodied individuals suggesting energy
      expenditure (EE) may be reduced in experienced individuals. With knowledge of the
      energy expended during wheelchair propulsion, nutritional recommendations can be
      provided for individuals in their early stages of rehabilitation and for
      habituated wheelchair users. AIM: To investigate the effects of experience on EE
      during wheelchair propulsion at fixed power outputs (PO's). DESIGN: This was an
      experimental study. SETTING: The experiment was conducted in a controlled
      University laboratory. POPULATION: Thirty-one individuals took part in this
      study. METHODS: Participants were assigned to a group in accordance to their
      wheelchair propulsion experience: 1) novice able-bodied individuals (NOV; N.=11),
      2) able-bodied individuals habituated to three weeks practice (PRAC; N.=11) and
      3) experienced paraplegic daily-wheelchair users (EXP; N.=9). Oxygen uptake, EE,
      GE% and HR were measured during wheelchair propulsion on a motorised treadmill at
      10, 18 and 26 W. RESULTS: Energy expenditure analysis revealed a significant main
      effect of PO and group (P<0.01) and a significant group by PO interaction
      (P<0.01). Follow-up pair-wise comparisons revealed significantly lower EE in EXP
      compared to both other groups (P<0.01), but no difference was shown between NOV
      and PRAC (P=0.15). A lower relative EE of 20, 22 and 32% was reported in the EXP
      group compared to the NOV group at 10, 18 and 26 W respectively. In comparison to
      the PRAC group, the EE of the EXP group was 10, 16 and 26% lower in relative
      terms at the same PO's respectively. CONCLUSION: The EXP expended less EE
      compared to both NOV and PRAC. CLINICAL REHABILITATION IMPACT: This finding has
      great implications for nutritionists and health care professionals working in the
      field of physical activity and weight management since the EE is influenced by
      experience.

PMID- 23558702
TI  - Role of the physical and rehabilitation medicine specialist regarding of children
      and adolescents with acquired brain injury.
AB  - Acquired brain injury (ABI) is one of the most common causes of mortality and
      severe disability in children and adolescents. Those with ABI may suffer any of a
      wide range of disorders that may limit their activity, their participation in
      family and school life, and their involvement in society in general. This paper
      describes the different stages of recovery - hospitalisation, preparing for
      discharge, and long term follow-up, in which PRM specialists are involved.
      Although the involvement of the PRM specialist is important in all three stages,
      it is during the latter two stages when his or her expertise is particularly
      important. An interdisciplinary care team - which the PRM specialist is well
      placed to lead - is required if the best results are to be achieved.

PMID- 23558703
TI  - Role, indications, and controversies of antidepressant therapy in chronic stroke
      patients.
AB  - Antidepressants are a heterogeneous class of drugs that have been developed for
      the treatment of mood disorders. In the past several years, they have been used
      in poststroke survivors to treat poststroke depression, central poststroke pain,
      and poststroke fatigue and as an adjuvant for functional recovery and cognitive
      function. However, there are still some relevant points to clarify regarding the
      real role of antdidepressants in stroke patients and further researches are
      needed to deeply explore their effects on rehabilitation results.

PMID- 23558704
TI  - Amphetamine and post-stroke rehabilitation: indications and controversies.
AB  - There is robust evidence for amphetamine (AMPH) facilitated recovery from
      behavioral deficits in animal models of stroke. Following experimental lesions,
      numerous studies of motor, somatosensory and vision recovery show AMPH
      accelerates the rate of recovery when paired with relevant behavioral experience.
      While the experimental literature continues to mount for an AMPH effect, the
      translation to clinical studies has been far less clear. This is due in part to
      the inherent difficulty of extrapolating results in animals to humans; however,
      there is much controversy regarding how the basic science data is interpreted for
      the design of human clinical trials. This review will: overview noteworthy
      experimental studies that have strong implications for human rehabilitation;
      describe the blinded drug/placebo clinical trials administering AMPH to enhance
      recovery of motor and language deficits post-stroke published to date; discuss
      the various complexities and controversies of designing clinical trials which may
      affect response/non-response to pharmacologic agents and conclude with
      suggestions of critical questions still to be answered for the rehabilitation
      specialist.

PMID- 23558705
TI  - Role, indications and controversies of levodopa administration in chronic stroke
      patients.
AB  - Stroke leaves many patients disabled even after rehabilitative training,
      representing a major cause of disability. Several approaches to improve outcomes
      have been attempted in recent years, with only relative benefit. Emerging
      evidences show a potential role of pharmacological intervention to enhance motor
      recovery after stroke. Contrasting evidence are coming from experimental and
      clinical studies, so far, and pharmacological intervention during rehabilitation
      represents a major controversial in neurorehabilitation. Dopaminergic stimulation
      appears as one of the most promising way to improve motor recovery. Subject of
      this paper will be the ratio underlying the clinical use of levodopa in chronic
      stroke patients, trying to outline the most convincing evidences about a
      potential role of this drug in rehabilitative strategies.

PMID- 23558706
TI  - Nervous control of reproduction in Octopus vulgaris: a new model.
AB  - The classic study of Wells and Wells on the control of reproduction in Octopus
      demonstrated that the activity of the subpedunculate lobe of the brain and
      environmental illumination both inhibit the release of an unknown gonadotropin
      from the optic gland. This inhibitory control may be exerted by the neuropeptide
      Phe-Met-Arg-Phe-NH2 (FMRFamide). It was later demonstrated that the olfactory
      lobe is also likely to be involved in the control of optic gland activity. The
      presence of gonadotropin-releasing hormone in the olfactory lobe suggested that
      it might exert an excitatory action on optic gland activity. Other neuropeptides
      have now been localised in the olfactory lobe: neuropeptide Y, galanin,
      corticotropin-releasing factor, Ala-Pro-Gly-Trp-NH2 (APGWamide), as well as
      steroidogenic enzymes and an oestrogen receptor orthologue. This supports the
      hypothesis that this lobe may also play a part in the control of reproduction in
      Octopus. The olfactory lobe receives distant chemical stimuli and also appears to
      be an integrative centre containing a variety of neuropeptides involved in
      controlling the onset of sexual maturation of Octopus, via the optic gland
      hormone. This review attempts to summarise current knowledge about the role of
      the olfactory lobe and optic gland in the control of sexual maturation in
      Octopus, in the light of new findings and in the context of molluscan comparative
      physiology.

PMID- 23558707
TI  - Sputum plasminogen activator inhibitor-1 elevation by oxidative stress-dependent
      nuclear factor-kappaB activation in COPD.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is an important regulator
      of fibrinolysis at sites of vascular injury and thrombus formation. Recently,
      sputum PAI-1 was reported to be elevated in COPD. However, the mechanism of PAI-1
      elevation in COPD has yet to be clarified. Here, we show that PAI-1 elevation in
      COPD is closely associated with oxidative stress-induced nuclear factor kappaB
      (NF-kappaB) activation. METHODS: Patients and control subjects were recruited
      from the outpatient department of Royal Brompton Hospital, local general
      practice, and the National Heart and Lung Institute. Sputum samples were
      obtained, and sputum sample processing was performed to obtain sputum
      supernatants and sputum macrophages. RESULTS: The mean PAI-1 level in COPD sputum
      (1.92 +/- 3.11 ng/mL, n = 32) was higher than that of both age-matched smokers
      without COPD (0.48 +/- 0.63 ng/mL, n = 11) and healthy nonsmokers (0.55 +/- 1.11
      ng/mL, n = 9). Sputum PAI-1 significantly correlated with sputum malondialdehyde
      (MDA) in COPD (r = 0.59, P < .001). In addition, NF-kappaB activity in sputum
      macrophages (three control and seven COPD subjects) significantly correlated with
      both sputum PAI-1 (r = 0.72, P < .05) and sputum MDA (r = 0.78, P < .01). An in
      vitro study showed that both hydrogen peroxide and cigarette smoke-conditioned
      medium induced PAI-1 production in A549 cells, and the production was inhibited
      by an inhibitor of I kappaB kinase-beta in a concentration-dependent manner.
      Furthermore, histone deacetylase 2 (HDAC2) knockdown by RNA interference, a mimic
      of oxidative-stress-dependent HDAC2 reduction, enhanced tumor necrosis factor
      alpha-induced PAI-1 induction (half maximal effective concentration [EC50], 0.64
      +/- 0.19 ng/mL in HDAC2-KD, 7.64 +/- 3.70 ng/mL in control) concomitant with
      enhancement of NF-kappaB p65 acetylation and NF-kappaB DNA-binding activity.
      CONCLUSIONS: Oxidative stress, directly or indirectly via HDAC reduction, plays a
      role in PAI-1 expression in COPD via activation of NF- kappa B.

PMID- 23558708
TI  - miR-200b targets GATA-4 during cell growth and differentiation.
AB  - GATA-4 is an important transcription factor involved in several developmental
      processes of the heart, such as cardiac myocyte proliferation, differentiation
      and survival. The precise mechanisms underlying the regulation of GATA-4 remain
      unclear, this is especially true for the mechanisms that mediate the post
      transcriptional regulation of GATA-4. Here, we demonstrate that miR-200b, a
      member of the miR-200 family, is a critical regulator of GATA-4. Overexpression
      of miR-200b leads to the downregulation of GATA-4 mRNA and a decrease in GATA-4
      protein levels. Moreover, miR-200b not only inhibits cell growth and
      differentiation but also reverses the growth response mediated by GATA-4, whereas
      depletion of miR-200b leads to a slight reversal of the anti-growth response
      achieved by knocking down endogenous GATA-4. More importantly, the cell cycle
      associated gene cyclin D1, which is a downstream target of GATA-4, is also
      regulated by miR-200b. Thus, miR-200b targets GATA-4 to downregulate the
      expression of cyclin D1 and myosin heavy chain (MHC), thereby regulating cell
      growth and differentiation.

PMID- 23558709
TI  - Alterations in NK cell phenotype in relation to liver steatosis in children with
      chronic hepatitis C.
AB  - NK cells were found to play an important role in liver fibrosis, a process
      commonly seen in a chronic liver disease such as chronic hepatitis C (CHC). The
      aim of this study was to evaluate potential differences in relation to coexisting
      liver steatosis in children with chronic hepatitis C. The study group consisted
      of 31 children with chronic hepatitis, aged 7-18 years (mean = 15 +/- 2 years).
      Blood samples were taken prior to liver biopsy. The METAVIR scale was used for
      histological evaluation. Peripheral lymphocytes were subjected to monoclonal
      antibodies to CD56 antigen, KIRs and NKG2D antigens. Cells were assayed by flow
      cytometry for the ratio of positive cells and mean fluorescence intensity (MFI).
      Results were evaluated regarding the presence of liver steatosis. Significantly
      higher mean AST activity as well as higher AST-to-platelets ratio index (APRI)
      was observed in a group of children with coexisting liver steatosis. These
      children had significantly higher MFI for CD158e and lower MFI for NKG2D. All CHC
      patients had significantly higher MFI for NKG2D than the controls. The proportion
      of cells with expression of CD158i, KIR2D and APRI was found independent
      predictors of liver steatosis in univariate analysis and body mass index in
      logistic regression. The expression of NK cell receptors is altered in coexisting
      steatosis that may influence long-term prognosis in CHC.

PMID- 23558710
TI  - Poverty as a contextual factor affecting sexual health behavior among female sex
      workers in India.
AB  - A thorough understanding of the environmental and structural factors that
      precipitate unsafe sexual practices is necessary for HIV/AIDS-prevention research
      among high-risk population groups like commercial sex workers. I examined how
      poverty contextualizes sexual health behavior, including condom compliance among
      commercial female sex workers in a red light district in Calcutta, India. For my
      research I did an ethnographic study and conducted in-depth interviews of 37
      commercial female sex workers. I found that poverty, instead of serving as a
      catalyst for poor health choices among sex workers, acted as an impetus for
      pursuing safe sex practices and remaining healthy. The results indicate that sex
      work, poverty, and health do not always have a paradoxical relationship.

PMID- 23558711
TI  - Gay men's explanations of health and how to improve it.
AB  - Little is known about the health views of gay men. In this article we report on
      how gay men explained health and the ways they discussed how health for gay men
      can be improved. We conducted a thematic analysis of data collected from 45 gay
      men in 11 focus groups and identified that health was mainly explained in
      individual terms, as were the ways to improve health (personal health care
      services and health promotion). The second way health was explained drew on
      social and community factors, with the societal acceptance of gay men being
      reported as essential for health improvements. These individual and
      social/community approaches were in tension; overall, the individualized
      approaches dominated. In line with other theorizing in health, we argue that
      appropriate policy and service provision to meet the health needs of gay men
      require greater acknowledgment of the social and community explanations of health
      and ways of improving health.

PMID- 23558712
TI  - Women's experiences of coping with pregnancy termination for fetal abnormality.
AB  - Pregnancy termination for fetal abnormality (TFA) can have significant
      psychological consequences. Most previous research has been focused on measuring
      the psychological outcomes of TFA, and little is known about the coping
      strategies involved. In this article, we report on women's coping strategies used
      during and after the procedure. Our account is based on experiences of 27 women
      who completed an online survey. We analyzed the data using interpretative
      phenomenological analysis. Coping comprised four structures, consistent across
      time points: support, acceptance, avoidance, and meaning attribution. Women
      mostly used adaptive coping strategies but reported inadequacies in aftercare,
      which challenged their resources. The study's findings indicate the need to
      provide sensitive, nondirective care rooted in the acknowledgment of the unique
      nature of TFA. Enabling women to reciprocate for emotional support, promoting
      adaptive coping strategies, highlighting the potential value of spending time
      with the baby, and providing long-term support (including during subsequent
      pregnancies) might promote psychological adjustment to TFA.

PMID- 23558713
TI  - The gendered construction and experience of difficulties and rewards in cancer
      care.
AB  - Women cancer carers have consistently been found to report higher levels of
      distress than men carers. However, there is little understanding of the
      mechanisms underlying these gender differences in distress, and a neglect of
      rewarding aspects of care. We conducted in-depth semistructured interviews with
      53 informal cancer carers, 34 women and 19 men, to examine difficult and
      rewarding aspects of cancer care. Thematic analysis was used to analyze the
      transcripts. Women were more likely to report negative changes in the
      relationship with the person with cancer; neglect of self, social isolation, and
      physical health consequences; anxiety; personal strength and growth; and to
      position caring as a privilege. Men were more likely to report increased
      relational closeness with the person with cancer, and the burden of additional
      responsibilities within the home as a difficult aspect of caring. We interpret
      these findings in relation to a social constructionist analysis of gender roles.

PMID- 23558714
TI  - Management of esophageal perforation in 120 consecutive patients: clinical impact
      of a structured treatment algorithm.
AB  - INTRODUCTION: The therapy of esophageal perforation is still challenging. The aim
      of this study was to assess the etiology, specific treatment, and outcome of
      esophageal disruption in order to generate an optimal therapeutic approach to
      improve patient's outcome. METHODS: We reviewed the cases of 120 consecutive
      patients with esophageal perforation treated within 10 years. RESULTS: Iatrogenic
      perforation was the most frequent cause of esophageal perforation (58.3 %);
      Boerhaave's syndrome was detected in 15 cases (6.8 %). Surgery was performed in
      66 patients (55 %), 17 (14 %) patients received conservative treatment and 37 (31
      %) patients underwent endoscopic stenting after tumorous perforation.
      Statistically significant impact on mean survival had Boerhaave's syndrome (p =
      0.005), initial sepsis (p = 0.002), pleural effusion/empyema (p = 0.001),
      mediastinitis (p = 0.003), peritonitis (p = 0.001), and redo-surgery (p = 0.000).
      Overall mortality rate was 11.7 %, in the esophagectomy group 17 % and in the
      patients with Boerhaave's syndrome 33.3 %. CONCLUSIONS: An approach considering
      etiology and extent of perforation, diagnostic delay, and septic status is
      required to improve patient's outcome. Primary repair is feasible in patients
      without intrinsic esophageal disease and evidence of sepsis. The greater the
      diagnostic delay, the more the destruction of the esophageal wall especially in
      the case of septic esophageal disease, thus the stronger the argument for
      esophagectomy if anatomically and/or oncologically possible.

PMID- 23558715
TI  - Neuroendocrine tumors arising in Meckel's diverticula: frequency of advanced
      disease warrants aggressive management.
AB  - BACKGROUND: Meckel's diverticulum is a common anomaly of the GI tract, which
      occasionally gives rise to cancer. The most frequent tumors affecting these
      diverticula are neuroendocrine tumors (NETs), and whether these should be treated
      in similar fashion as small bowel NETs or appendiceal NETs is unclear. METHODS: A
      retrospective chart review was conducted at a single academic medical center
      between 1998 and 2012. Demographic, radiologic, biochemical, and
      clinicopathologic data were collected as well as status at last follow-up.
      RESULTS: Seven patients were identified with NETs involving Meckel's diverticula,
      including one with limited information other than management of her late
      metastases. Of the six other patients, all had involvement of regional nodes,
      including three patients with tumors <2 cm in size, and four had liver metastases
      at presentation. CONCLUSIONS: NETs in Meckel's diverticula are rare tumors, but
      when they develop, are often associated with nodal metastases and liver
      metastases, even when the tumors are small. Therefore, optimal management of
      these NETs is small bowel resection with regional lymphadenectomy and debulking
      of liver metastases where feasible.

PMID- 23558716
TI  - [Anesthesia for electroconvulsive therapy].
AB  - Electroconvulsive therapy is a well-established form of treatment for a broad
      spectrum of severe psychiatric disorders. The treatment, in which a generalized
      epileptic seizure is provoked by electrical stimulation of the brain, is
      performed with the patient under anesthesia and muscle relaxation. Therefore,
      sufficient knowledge of the physiological and pharmacological characteristics is
      an essential requirement for safe anesthesia. The following review is intended to
      provide some new aspects of the procedure and management of anesthesia.

PMID- 23558717
TI  - [Quality of results of therapy of acute respiratory failure : changes over a
      period of two decades].
AB  - Progress in intensive care (ICU) treatment of acute respiratory distress syndrome
      (ARDS) over the last 20 years includes the introduction of extracorporeal
      membrane oxygenation (ECMO) for CO2 removal and the widespread use of evidence
      based lung-protective ventilatory strategies. Little is known, however, about
      whether these changes have resulted in improvements in short-term and long-term
      outcome of acute respiratory distress syndrome (ARDS) within the two decades
      after introduction. In a retrospective study 167 long-term survivors of severe
      ARDS who were transferred to the clinic for anesthesiology of the University of
      Munich, Campus Grobetahadern by means of specialized intensive care unit (ICU)
      transport teams and treated over a period of 20 years (1985-2005) were evaluated
      to investigate whether significant improvements in outcome as a consequence of
      the above mentioned progress in ARDS therapy have occurred. The ARDS patient
      cohort studied was characterized with regard to demographic variables, initial
      acute physiology and chronic health evaluation (APACHE) II score, duration of ICU
      treatment, the duration of mechanical ventilation and mortality. Data on long
      term outcome were collected in a subcohort (n = 125) of patients who responded to
      mailed questionnaires and included health-related quality of life (HRQL, SF-36
      questionnaire), symptoms of post-traumatic stress disorder (PTSD), traumatic
      memories from ICU treatment (PTSS-10 instrument) and current state of employment.
      During the observation period no significant changes regarding patient age (39 +/
      16 years, mean +/- SD), disease severity on admission to the ICU (APACHE II
      scores 22 +/- 5), duration of ICU treatment (47 +/- 39 days) or duration of
      mechanical ventilation (39 +/- 38 days) were found. Overall ICU mortality during
      the two decades was 37.3 % (range 25.0 %-38.1 %) between 1995 and 2001 and a non
      significant increase in values between 36.8 % and 58.3 % during the time interval
      from 2002 und 2005. The paO2/FIO2-ratio on ICU admittance improved significantly
      between 1990 and 2000 (69 +/- 5 between 1990 and 1994 versus 101 +/- 12 between
      1995 and 2000, p < 0.01) and remained nearly unchanged thereafter. Long-term
      outcome was evaluated on average 5.0 +/- 3.1 years after discharge from the ICU.
      During the time period between 1985 and 1994 survivors of ARDS showed significant
      impairments in all 8 categories of the SF-36 HRQL instrument when compared to an
      age and sex-matched normal population with maximal differences regarding physical
      function (z = -1.01), general health perception (z = -1.17) and mental health (z
      = -1.3). Patients who were treated from 1995 to 2005 were still impaired in 7 out
      of 8 categories of HRQL but reported significantly better mental health (49.6 +/-
      16.5 vs. 68.6 +/- 17.8, p < 0,01) and better physical function than individuals
      from the previous decade (49.6 +/- 16.5 vs. 73.4 +/- 27.5, p = 0,03). The
      difference of mental health was no longer significant when compared to a healthy
      age and sex matched control group (p = 0.14) but the difference in physical
      function still was (z = -0.48, p < 0.01). The incidence of severe post-traumatic
      stress defined as a PTSS-10 score >= 35 was 20.4 % and remained unchanged
      throughout the 2 decades of observation. The PTSS-10 scores correlated with the
      number of traumatic memories present (r = 0.43, p < 0.01, n = 125). More than 50
      % of long-term survivors were able to return to full time work with no
      significant changes during the 2 decades of observation. The introduction of new
      modalities of ARDS treatment were associated with higher paO2/FIO2-ratios on ICU
      admittance but had no effect on short-term outcomes including duration of ICU
      therapy, mechanical ventilation or mortality. The ARDS patients are still at risk
      for post-traumatic stress and persistent impairments in HRQL. Apart from some
      improvements in HRQL, the outcome of ARDS therapy remained largely unchanged
      during two decades.

PMID- 23558719
TI  - [Subdural hematoma after dural puncture: fateful complication of epidural
      anesthesia].
AB  - Subdural hematoma may occur as rare, although intervention- specific
      complications of accidental dural puncture by neuroaxial block. Bleeding may be
      caused by rapid cerebrospinal fluid loss related to traction on fragile
      intracranial bridging veins. This article reports a case of postdural puncture
      headache in a 43-year-old woman after accidental dural puncture during attempted
      placement of an epidural catheter for induction of abortion. Bed rest,
      analgesics, theophylline and hydration were to no avail and only a blood patch
      improved the headaches. The patient presented 7 weeks later with headache and
      left-sided hemiplegia. Magnetic resonance imaging showed a right frontoparietal
      subdural intracranial hematoma which had to be surgically evacuated. The patient
      recovered completely. Intracranial hematoma is a rare but serious complication of
      central neuroaxial block. According to current German jurisdiction this risk must
      be addressed when informed consent is obtained. Intracranial hematoma should be
      considered in the differential diagnosis of atypical headache and neurological
      signs (e.g. focal motor and sensory deficits and seizures) following neuroaxial
      block and adequate image diagnostics should be carried out without delay.

PMID- 23558718
TI  - [International guidelines of the Surviving Sepsis Campaign : update 2012].
AB  - An update of the international guidelines for therapy of sepsis was published in
      February 2012 by the Surviving Sepsis Campaign (SSC). The update includes a
      further development of the guidelines from 2004 and 2008. The guidelines are
      divided into three sections, sepsis-specific therapeutic measures,
      recommendations on general intensive care measures for sepsis and finally special
      features of sepsis in pediatric intensive care medicine are presented in detail.
      This article discusses the most important amendments in the first two sections
      and delving deeper into the guidelines.

PMID- 23558720
TI  - [Disorders of serum sodium in emergency patients : salt in the soup of emergency
      medicine].
AB  - Electrolyte disorders are common and potentially fatal laboratory findings in
      emergency patients. Approximately 20 % of patients in the emergency department
      present with either hyponatremia or hypernatremia. Recently it was shown that
      disorders of serum sodium are not only an expression of the severity of the
      underlying disease but independent predictors for the outcome of patients. They
      directly influence patient daily life by causing not only gait and concentration
      disturbances but also an increased tendency to fall together with a reduced bone
      mass. Given these new data it is even more important to detect and adequately
      correct dysnatremia in patients in the emergency department. Acute, symptomatic
      dysnatremia should be corrected promptly by use of 3 % NaCl for hyponatremia and
      5 % glucose for hypernatremia. A close monitoring of serum sodium concentration
      is, however, essential in any case of correction of hyponatremia or hypernatremia
      in order to avoid rapid overcorrection and subsequent complications. A profound
      knowledge of the mechanisms underlying the development of hyponatremia, e.g.
      diuretics, syndrome of inappropriate antidiuretic hormone secretion (SIADH),
      heart failure and cirrhosis of the liver and hypernatremia, e.g. dehydration,
      infusions, diuretics and osmotic diuresis is essential. The present article
      describes the epidemiology, etiology and correction of hyponatremia and
      hypernatremia on the basis of current knowledge with special emphasis on
      emergency department patients.

PMID- 23558721
TI  - [Transfusion-related acute lung injury].
AB  - Transfusion-related acute lung injury (TRALI) developed into the leading cause of
      transfusion-related morbidity and mortality after the first description by
      Popovsky et al. approximately three decades ago. It was the most frequent reason
      for transfusion-related fatalities worldwide before implementation of risk
      minimization strategies by donor selection. Plasma-rich blood products, such as
      fresh frozen plasma and apheresis platelets seem to be the leading triggers of
      TRALI. Hypoxemia and development of pulmonary edema within 6 h of transfusion are
      the diagnostic criteria for TRALI. The differentiation between cardiac failure
      and other transfusion-related lung injuries, such astransfusion-associated
      circulatory overload ( TACO) is difficult and causal treatment is not available.
      Therapy is based on supportive measures, such as oxygen insufflationor mechanical
      ventilation. The exactly pathogenesis is still unknown but the most propagated
      hypothesis is the two-event-model. Neutrophils are primed by the underlying
      condition, e.g. sepsis or trauma during the first event and these primed
      neutrophils are activated by transfused leukoagglutinating antibodies (immunogen)
      or bioreactive mediators (non-immunogen) during the second-event. Transfusion of
      leukoagglutinating antibodies from female donors with one or more previous
      pregnancies is the most frequent reason. No more TRALI fatalities were reported
      after implementation of the donor selection in Germany in 2009.

PMID- 23558723
TI  - Sporadic intracranial haemangioblastomas: surgical outcome in a single
      institution series.
AB  - BACKGROUND: Haemangioblastomas are benign vascular tumours that may appear
      sporadically or in von Hippel-Lindau disease. Despite their higher incidence,
      sporadic haemangioblastomas have been less studied than syndromic ones. In this
      article, we evaluate the specific features, outcome and quality of life of
      patients with intracranial sporadic haemangioblastomas (ISHs) operated on in our
      institution. METHODS: Between 1998 and 2010, 38 patients harbouring 38 ISHs were
      operated on in our department. Their clinical, biological, radiological and
      surgical features were retrospectively reviewed. All patients were contacted for
      a quality-of-life (QOL) survey assessed by the Short Form 36 questionnaire
      (SF36). The mean duration of follow-up was 40 months (13-108 months). RESULTS:
      ISH represented 0.9 % of primary intracranial neoplasms treated in our centre
      during this period. Patients comprised 23 men and 15 women with a mean age of 47
      years. None had polycythaemia. Cerebellar locations accounted for 79 % of ISHs,
      and brainstem ISH with involvement of the floor of the fourth ventricle
      represented 11 % of ISHs. At last follow-up, two patients harbouring solid
      medulla oblongata haemangioblastoma had died following severe bulbar syndrome and
      five patients had died of unrelated causes. One patient had multiple surgeries
      for three recurrences. Tumoral control was achieved in all cases at last follow
      up. Results of the SF-36 questionnaire were as follows: median physical
      functioning score 100 (range 0-100), median physical problems score 100 (range 0
      100), median bodily pain score 100 (range 45-100), median social functioning
      score 100 (range 25-100), median general mental health score 84 (range 40-92),
      median emotional problems score 100 (range 0-100), median vitality score 70
      (range 35-80) and median general health perceptions score 70 (range 35-100). Mean
      QOL scores were similar to the general healthy population. CONCLUSION: Surgery of
      ISH provides good QOL and tumoral control except for those located in the medulla
      oblongata. We recommend considering a careful multimodal therapeutic approach,
      including radiosurgery for these specific locations.

PMID- 23558724
TI  - Estimated low risk of rupture of small-sized unruptured intracranial aneurysms
      (UIAs) in relation to intracranial aneurysms in patients with subarachnoid
      haemorrhage.
AB  - OBJECTIVE: International guidelines for the management of unruptured intracranial
      aneurysms (UIAs) recommend observation in aneurysms <10 mm due to the estimated
      low risk of rupture. The aim of our study was analyse the data of recently
      treated patients with ruptured cerebral aneurysms with the special focus on size
      and configuration in view of the frequency scale in a daily routine setting.
      METHODS: We reviewed the data of all patients with aneurysmal subarachnoid
      haemorrhage (SAH) during the last 24 months at our institution. Configuration and
      size of the aneurysms were measured. Clinical data were collected using the
      following classifications for analysis: Hunt and Hess (H&H), modified Rankin
      Scale (mRS) and Fisher classification. RESULTS: Data of 135 patients with
      aneurysmal SAH (98 women, 37 men; ratio 2.6:1) were analysed. Analysis showed
      that 19 aneurysms (14 %) were >10 mm (mean size, 19.2 mm) and 116 aneurysms (85.9
      %) <10 mm (mean size, 6.2 mm). In total, 112 were categorised as berry-like
      configured aneurysms (n = 113 <10 mm, n = 3 >10 mm), 18 as multi-lobar (n = 16
      <10 mm, n = 2 >10 mm) and 5 as fusiform (n = 4 <10 mm, n = 1, >10 mm).
      CONCLUSION: Since the results of our study showed that the majority of the
      aneurysms are <10 mm (mean, 6.2 mm), it is justified to challenge the
      recommendations of the international guidelines in a daily routine setting. We
      believe that the published data are not convincing enough to play a guidance role
      in daily routine. Due to improving surgical and endovascular techniques with
      satisfying results and the high number of ruptured small aneurysms, we believe a
      change in attitude in management of small-sized aneurysms is needed. Further
      diagnostic models are needed to determine the risk of rupture of intracranial
      aneurysms properly to obtain adequate treatment for UIAs.

PMID- 23558725
TI  - Intracranial meningiomas and neurofibromatosis type 2.
AB  - PURPOSE: In spite of the few clinical studies regarding the occurrence of
      intracranial meningiomas, their prognosis in neurofibromatosis type 2 (NF2) has
      not been accurately assessed and their management remains controversial. This
      study aims to compare NF2 patients with intracranial meningiomas to those
      without, and consequently to identify prognostic factors in attempt to improve
      the management of these tumors. METHODS: This retrospective study includes a
      total of 80 NF2 patients followed at Lille Hospital Center between 1987 and 2011.
      The diagnosis of NF2 was confirmed either because the patient met the Manchester
      criteria or by the presence of genetic mutation. Clinical, radiological and
      genetic data were retrospectively recorded and analyzed. Patients underwent
      annual cranial and spinal MRI. Both location and size of each tumor were
      reported. RESULTS: The mean follow-up period was 8.8 years (range 1-24 years; SD:
      +/-0.8) and the mean age at diagnosis was 27.2 years (range 6-73 years; SD: +/
      1.7). Among all patients, 34 harbored intracranial meningiomas. Patients with
      intracranial meningiomas had a higher number of intracranial schwannomas, spinal
      tumors and cutaneous tumors (p < 0.05). They underwent more surgical procedures
      (p < 0.012). Twenty five intracranial meningiomas were surgically removed in 17
      patients. The decision to perform surgery was taken in 10 cases for symptomatic
      tumors and in 15 cases for growing asymptomatic tumors determined by radiology.
      The histological analysis found a high rate of fibroblastic, transitional or
      grade 2 meningiomas preferentially located at the cerebri falx. CONCLUSION:
      Intracranial meningiomas are common in NF2. They are associated with poor
      prognosis factors. Clinical and radiological monitoring could lead to early
      treatment of these tumors both when clinical symptoms are present and in case of
      proven radiological evolution, and thus trying to maintain a favorable functional
      prognosis for as long as possible.

PMID- 23558726
TI  - Matricide and stepmatricide victims and offenders: an empirical analysis of U.S.
      arrest data.
AB  - Almost all of the clinical and empirical literature on female parricide victims
      focuses on mothers killed, with only little information available on stepmothers
      murdered. This study is the first to compare the victim, offender, and case
      correlates in incidents when mothers and stepmothers were killed. Supplementary
      Homicide Report Data for 1976-2007 were used to investigate similarities and
      differences between the two female victim types in the United States.
      Similarities between stepmothers and mothers included that more than 70% were
      White and killed in single victim, single offender incidents. Their killers were
      adult sons in between 67% and 87% of incidents. Several significant differences
      emerged with respect to age, involvement in multiple offender incidents, and
      weapon use. Stepmothers and their stepchildren, relative to mothers and their
      offspring, were significantly younger. Sixty-four percent of stepchildren,
      compared with 35% of biological children, were under age 25 at the time of their
      arrest for murder. A higher percentage of juveniles than adult killers was
      involved in multiple offender (MO) incidents involving mothers. Relative to their
      male counterparts, higher percentages of female juveniles were involved in MO
      incidents involving the deaths of mothers and stepmothers. A higher proportion of
      female adults, relative to their male counterparts, were involved in MO matricide
      incidents. Offenders who killed stepmothers, relative to those who killed
      mothers, were significantly more likely to use guns. Juvenile matricide offenders
      were significantly more likely to use firearms than their adult counterparts.
      Possible reasons for the differences are discussed in the conclusion.

PMID- 23558727
TI  - Squamous cell carcinomas in patients with Fanconi anemia and dyskeratosis
      congenita: a search for human papillomavirus.
AB  - Patients with Fanconi anemia (FA) and dyskeratosis congenita (DC) are at high
      risk of head and neck squamous cell carcinomas (HNSCC) and anogenital squamous
      cell carcinomas (SCC). In the general population, these sites (particularly
      oropharyngeal SCC) may be associated with infection with human papillomavirus
      (HPV). In FA and DC, however, the majority of HNSCC occur in the oral cavity. We
      investigated the HPV status of HNSCC and vulvar SCC from nine patients with FA
      and four with DC using a very sensitive PCR assay, and found HPV16 DNA in only a
      single vulvar tumor from one patient with FA, and in none of the HNSCC. These
      results suggest that HPV may not be the cause of SCC in patients with FA or DC,
      and that vaccination may not reduce the incidence of HNSCC in these patients. 

PMID- 23558728
TI  - Effect of brightness in the evaluation of lumbar pedicular screws position:
      clinical study.
AB  - Artifact may lead to confusion when evaluating postoperative CT scans of lumbar
      pedicle screws. The aim of our study was to develop a specific metal artifact
      reduction image protocol, in order to reduce metal artifact caused by titanium
      pedicular screw in patients undergoing lumbar pathology by lumbar fusion.
      Therefore, the reduction in metal artifacts in lumbar pedicle screws allows
      surgeons to do an accurate diagnosis of the exact placement of inserted pedicle
      screws, minimizes false reexploration, and maximizes proper and prompt treatment
      of misplaced screw. In a first step, we performed a retrospective study of 103
      titanium alloy pedicle screws in patients undergoing a lumbar instrumented fusion
      for treatment for degenerative disease. CT scan was performed postoperatively
      evaluating the possible overdimension caused by artifact. In a second step, a
      prospective study was performed using a 64-slice multidetector-row computed
      tomography (MDCT) in 104 titanium alloy pedicle screws in patients undergoing a
      lumbar instrumented fusion for treatment for degenerative disease. Our results
      show that on the group of sequential CT scan, mean overdimension (on each side)
      due to brightness was 1.045 mm (SD 0.45). On the group of 64-slice multichannel
      CT, mean overdimension (on each side) due to brightness was 0.005 mm at the
      proximal part of the screw and 0.025 mm at the distal part of the screw. The
      results observed suggest that beam-hardening artifacts caused by the screw on CT
      after lumbar fusion are dramatically reduced by using specific metal artifact
      reduction image protocol in a 64-slice MDCT.

PMID- 23558729
TI  - Influence of the 2009 financial crisis on detection of advanced pulmonary
      tuberculosis in Osaka city, Japan: a cross-sectional study.
AB  - OBJECTIVE: To investigate the association between the economic recession and the
      detection of advanced cases of pulmonary tuberculosis in Osaka city from 2007 to
      2009. DESIGN: A repeated cross-sectional study. SETTING: Osaka city has been the
      highest tuberculosis burden area in Japan. After the previous global financial
      crisis, the unemployment rate in Osaka prefecture has deteriorated from 5.3% in
      2008 to 6.6% in 2009. PARTICIPANTS: During the study period, 3406 pulmonary
      tuberculosis cases were enrolled: 2530 males and 876 females; 1546 elderly cases
      (65 years and above) and 1860 young cases (under 65 years); 417 homeless cases
      and 2989 non-homeless cases. OUTCOME MEASURES: Patients' information included the
      sex, age, registry, health insurances, places of detection, sputum smear test
      results, patients' delay, doctors' delay and the grade of chest x-ray findings.
      They were statistically analysed between 2007 and 2008, two years before and just
      before the financial crisis, and between 2008 and 2009, just before and after the
      financial crisis. RESULTS: The total numbers of pulmonary tuberculosis cases were
      1172 in 2007, 1083 in 2008 and 1151 in 2009. In health examinations for non
      homeless people, higher number of cases in 2009 were sputum smear positive, had
      respiratory symptoms and showed advanced disease in chest x-rays than those in
      2008, with a longer patients' delay. On the contrary, in health examination for
      homeless people, fewer cases of advanced pulmonary tuberculosis were found in
      2009 than in 2008, with a shorter patients' delay. In clinical examinations,
      there was no trend towards a difference between non-homeless and homeless people.
      CONCLUSIONS: Although homeless people might be protected by public assistance,
      tuberculosis prevention and control need to be reinforced for the non-homeless
      population after the financial crisis.

PMID- 23558730
TI  - Juvenile Huntington's disease: a population-based study using the General
      Practice Research Database.
AB  - BACKGROUND: The juvenile form of Huntington's disease (HD) is a rare disorder.
      There are no population-based estimates of either its incidence or prevalence in
      any population in the world. The present study was undertaken to estimate the
      frequency of juvenile HD in the UK and to examine the range of pharmacological
      treatments used in its management. METHOD: The records of individuals under the
      age of 21 who had recorded diagnoses of HD were retrieved from the General
      Practice Research Database from 1990 through 2010. From these data estimates of
      incidence and prevalence were made as well as the specific treatments used in the
      treatment of its physical and psychological manifestations. RESULTS: 12 incident
      and 21 prevalent patients with juvenile HD were identified. The 21 prevalent
      cases included the 12 incident cases. The minimum population-based estimate of
      incidence is 0.70 (95% CI 0.36 to 1.22) per million patient-years. The minimum
      estimate of prevalence is 6.77/million (95% CI 5.60 to 8.12) per million patient
      years. Patients were most frequently prescribed antidepressants, hypnotics,
      antipsychotics and treatments for motor abnormalities. CONCLUSIONS: In the UK,
      juvenile HD is an extremely rare and complex disorder. The prescribing data
      demonstrate that the clinical management of juvenile HD is undertaken with no
      formal evidence base for the efficacy or safety of the treatments used. Research
      into the safety and efficacy of appropriate therapies is urgently required to
      offset the haphazard nature of prescribing. Multinational collaboration will be
      necessary to enrol sufficient numbers. Exploratory studies, though, should begin
      now.

PMID- 23558731
TI  - The high cost of diarrhoeal illness for urban slum households-a cost-recovery
      approach: a cohort study.
AB  - OBJECTIVES: Rapid urbanisation has often meant that public infrastructure has not
      kept pace with growth leading to urban slums with poor access to water and
      sanitation and high rates of diarrhoea with greater household costs due to
      illness. This study sought to determine the monetary cost of diarrhoea to urban
      slum households in Kaula Bandar slum in Mumbai, India. The study also tested the
      hypotheses that the cost of water and sanitation infrastructure may be surpassed
      by the cumulative costs of diarrhoea for households in an urban slum community.
      DESIGN: A cohort study using a baseline survey of a random sample followed by a
      systematic longitudinal household survey. The baseline survey was administered to
      a random sample of households. The systematic longitudinal survey was
      administered to every available household in the community with a case of
      diarrhoea for a period of 5 weeks. PARTICIPANTS: Every household in Kaula Bandar
      was approached for the longitudinal survey and all available and consenting
      adults were included. RESULTS: The direct cost of medical care for having at
      least one person in the household with diarrhoea was 205 rupees. Other direct
      costs brought total expenses to 291 rupees. Adding an average loss of 55 rupees
      per household from lost wages and monetising lost productivity from homemakers
      gave a total loss of 409 rupees per household. During the 5-week study period,
      this community lost an estimated 163 600 rupees or 3635 US dollars due to
      diarrhoeal illness. CONCLUSIONS: The lack of basic water and sanitation
      infrastructure is expensive for urban slum households in this community.
      Financing approaches that transfer that cost to infrastructure development to
      prevent illness may be feasible. These findings along with the myriad of
      unmeasured benefits of preventing diarrhoeal illness add to pressing arguments
      for investment in basic water and sanitation infrastructure.

PMID- 23558732
TI  - Junior doctor skill in the art of physical examination: a retrospective study of
      the medical admission note over four decades.
AB  - OBJECTIVES: To investigate the hypothesis that junior doctors' examination skills
      are deteriorating by assessing the medical admission note examination record.
      DESIGN: Retrospective study of the admission record. SETTING: Tertiary care
      hospital. METHODS: The admission records of 266 patients admitted to Wellington
      hospital between 1975 and 2011 were analysed, according to the total number of
      physical examination observations (PEOtot), examination of the relevant system
      pertaining to the presenting complaint (RelSystem) and the number of body systems
      examined (Nsystems). Subgroup analysis proceeded according to admission year,
      level of experience of the admitting doctor (registrar, house surgeon (HS) and
      trainee intern (TI)) and medical versus surgical admission notes. Further
      analysis investigated the trend over time in documentation with respect to
      cardiac murmurs, palpable liver, palpable spleen, carotid bruit, heart rate,
      funduscopy and apex beat location and character. RESULTS: PEOtot declined by 34%
      from 1975 to 2011. Surgical admission notes had 21% fewer observations than
      medical notes. RelSystem occurred in 94% of admissions, with no decline over
      time. Medical notes documented this more frequently than surgical notes (98% and
      86%, respectively). There were no differences between registrars and HS, except
      for the 2010s subgroup (97% and 65%, respectively). Nsystems declined over the
      study period. Medical admission notes documented more body systems than surgical
      notes. There were no differences between registrars, HSs and TIs. Fewer
      examinations were performed for palpable liver, palpable spleen, cardiac murmur
      and apex beat location and character over the study period. There was no temporal
      change in the positive findings of these observations or heart rate rounding.
      CONCLUSIONS: There has been a decline in the admission record at Wellington
      hospital between 1975 and 2011, implying a deterioration in local doctors'
      physical examination skills. Measures to counter this trend are discussed.

PMID- 23558733
TI  - General practitioners' prescribing behaviour as a determinant of poor persistence
      with inhaled corticosteroids in children with respiratory symptoms: mixed methods
      study.
AB  - OBJECTIVES: To evaluate general practitioners' (GPs') prescribing behaviour as a
      determinant of persistence with and adherence to inhaled corticosteroids (ICS) in
      children. DESIGN: Prospective observational study of persistence with and
      adherence to ICS followed by a focus group study of the GPs prescribing this
      treatment. SETTING: 7 primary care practices in the area of Zwolle, the
      Netherlands. PARTICIPANTS: 134 children aged 2-12 years had been prescribed ICS
      in the year before the study started by their 19 GPs. MAIN OUTCOME MEASURES:
      Patterns and motives of GPs' prescribing behaviour and the relationship with
      persistence with and adherence to ICS. RESULTS: GPs' prescribing behaviour was
      characterised by prescribing short courses of ICS to children with various
      respiratory symptoms without follow-up for making a diagnosis of asthma. This was
      driven by the GPs' pragmatic approach to deal with the large number of children
      with respiratory symptoms, and by beliefs about ICS which differed from currently
      available evidence. This prescribing behaviour was the main reason why 68 (51%)
      children did not persist with the use of ICS. In children with persistent use of
      ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was
      70% (41-84%), and was similar for patients with persistent asthma and children
      lacking a diagnosis or symptoms of asthma. CONCLUSIONS: Inappropriate
      prescription of ICS to children by GPs is common and drives the lack of
      persistence with ICS therapy in primary care. This finding should be taken into
      account when interpreting data from large prescription database studies.
      Improving primary healthcare providers' knowledge and competence in diagnosing
      and managing asthma in children is needed.

PMID- 23558734
TI  - A qualitative study of GP, NP and patient views about the use of rapid
      streptococcal antigen detection tests (RADTs) in primary care: 'swamped with sore
      throats?'.
AB  - OBJECTIVE: To explore patient and healthcare professionals' (HCP) views of
      clinical scores and rapid streptococcal antigen detection tests (RADTs) for acute
      sore throat. DESIGN: Qualitative semistructured interview study. SETTING: UK
      primary care. PARTICIPANTS: General practitioners (GPs), nurse practitioners
      (NPs) and patients from general practices across Hampshire, Oxfordshire and the
      West Midlands who were participating in the Primary Care Streptococcal Management
      (PRISM) study. METHOD: Semistructured, face-to-face and phone interviews were
      conducted with GPs, NPs and patients from general practices across Hampshire,
      Oxfordshire and the West Midlands. RESULTS: 51 participants took part in the
      study. Of these, 42 were HCPs (29 GPs and 13 NPs) and 9 were patients. HCPs could
      see a positive role for RADTs in terms of reassurance, as an educational tool for
      patients, and for aiding inexperienced practitioners, but also had major concerns
      about RADT use in clinical practice. Particular concerns included the validity of
      the tests (the role of other bacteria, and carrier states), the tension and
      possible disconnect with clinical assessment and intuition, the issues of time
      and resource use and the potential for medicalisation of self-limiting illness.
      In contrast, however, experience of using RADTs over time seemed to make some
      participants more positive about using the tests. Moreover, patients were much
      more positive about the place of RADTs in providing reassurance and in limiting
      their antibiotic use. CONCLUSIONS: It is unlikely that RADTs will have a
      (comfortable) place in clinical practice in the near future until health
      professionals' concerns are met, and they have direct experience of using them.
      The routine use of clinical scoring systems for acute upper respiratory illness
      also face important barriers related to clinicians' perceptions of their utility
      in the face of clinician experience and intuition.

PMID- 23558735
TI  - Socioeconomic characteristics of residential areas and risk of death: is
      variation in spatial units for analysis a source of heterogeneity in observed
      associations?
AB  - OBJECTIVES: Evidence on the association between the adverse socioeconomic
      characteristics of residential area and mortality is mixed. We examined whether
      the choice of spatial unit is critical in detecting this association. DESIGN:
      Register-linkage study. SETTING: Data were from the Finnish Public Sector study's
      register cohort. PARTICIPANTS: The place of residence of 146 600 cohort
      participants was linked to map grids and administrative areas, and they were
      followed up for mortality from 2000 to 2011. Residential area socioeconomic
      deprivation and household crowding were aggregated into five alternative areas
      based on map grids (250*250 m, 1*1 km and 10*10 km squares), and administrative
      borders (zip-code area and town). PRIMARY AND SECONDARY OUTCOME MEASURES: All
      cause mortality. RESULTS: For the 250*250 m area, mortality risk increased with
      increasing socioeconomic deprivation (HR for top vs bottom quintile 1.36, 95% CI
      1.21 to 1.52). This association was either weaker or missing when broader spatial
      units were used. For household crowding, excess mortality was observed across all
      spatial units, the HRs ranging from 1.14 (95% CI 1.03 to 1.25) for zip code, and
      1.21 (95% CI 1.11 to 1.31) for 250*250 m areas to 1.28 (95% CI 1.10 to 1.50) for
      10*10 km areas. CONCLUSIONS: Variation in spatial units for analysis is a source
      of heterogeneity in observed associations between residential area
      characteristics and risk of death.

PMID- 23558736
TI  - Executive functioning in children with unilateral cerebral palsy: protocol for a
      cross-sectional study.
AB  - INTRODUCTION: Early brain injury, as found in children with unilateral cerebral
      palsy (CP), may cause deficits in higher-order cognitive tasks known as executive
      functions (EF). EF has been conceptualised as comprised of four distinct yet
      inter-related components: (1) attentional control, (2) cognitive flexibility, (3)
      goal setting and (4) information processing. The aim of this study was to examine
      EF in children with unilateral CP and compare their performance with a typically
      developing reference group (TDC). The potential laterality effects of unilateral
      CP on EF will be explored, as will the relationship between the cognitive
      measures of EF, behavioural manifestations of EF, psychological functioning and
      clinical features of unilateral CP. METHODS AND ANALYSIS: This cross-sectional
      study aims to recruit a total of 42 children with unilateral CP (21 right
      unilateral CP and 21 left unilateral CP) and 21 TDC aged between 8 and 16 years.
      Clinical severity will be described for gross motor function and manual ability.
      Outcomes for cognitive EF measureswill include subtests from the Wechsler
      Intelligence Scale for Children-Fourth Edition, Delis-Kaplan Executive Function
      System, Rey Complex Figure Test and the Test of Everyday Attention for Children.
      Behavioural manifestations of EF will be assessed using the Behaviour Rating
      Inventory of Executive Function, Parent and Teacher versions. Psychological
      functioning will be examined using the Strengths and Difficulties Questionnaire.
      Between-groups differences will be examined in a series of one-way analyses of
      covariance and followed up using linear comparisons. An overall composite of
      cognitive EF measures will be created. Bivariate correlations between the EF
      composite and psychological measures will be calculated. ETHICS AND
      DISSEMINATION: This protocol describes a study that, to our knowledge, is the
      first to examine multiple components of EF using a cohort of children with
      unilateral CP. Exploration of potential laterality effects of EF among children
      with a congenital, unilateral brain injury is also novel. Possible relationships
      between EF and psychological functioning will also be investigated. Ethics have
      been obtained through the University of Queensland School of Psychology Ethics
      Committee and the Queensland Children's Health Services Human Research Ethics
      Committee. Results will be disseminated in peer reviewed publications and
      presentations at national and international conferences. This study is registered
      with the Australian New Zealand Clinical Trials Registry (ACTRN12611000263998).

PMID- 23558737
TI  - The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC):
      routine screening data for central Europe from a cohort study.
AB  - OBJECTIVES: Owing to novel therapy strategies in epidermal growth factor receptor
      (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has
      become crucial for routine diagnostics. Till date these data have been derived
      mostly from clinical trials, and thus collected in pre-selected populations. We
      therefore screened 'allcomers' with a newly diagnosed non-small cell lung
      carcinoma (NSCLC) for the frequencies of these mutations. DESIGN: A cohort study.
      SETTING: Lung cancer centre in a tertiary care hospital. PARTICIPANTS: Within 15
      months, a total of 552 cases with NSCLC were eligible for analysis. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Frequency of scrutinising exons 18, 19 and 21 for the
      presence of activating EGFR mutation and secondary codon 12 and 13 for activating
      KRAS mutations. RESULTS: Of the 552 patients, 27 (4.9%) showed a mutation of
      EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion
      L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among
      patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%);
      p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in
      women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an
      activating EGFR mutation were more likely to be from non-smokers (18/27; 67%)
      rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all
      cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases
      (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than
      non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001). CONCLUSIONS: We found a lower
      frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort
      as previously published. Taking our results into account, clinical trials may
      overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important
      selection biases.

PMID- 23558738
TI  - Photodynamic therapy for hilar bile duct cancer: clinical evidence for improved
      tumoricidal tissue penetration by temoporfin.
AB  - Photodynamic therapy (PDT) has been established for palliation of non-resectable
      hilar bile duct cancer (hBDC). Ablation of hBDC using porfimer (P-PDT) improves
      cholestasis and survival. However, the tumoricidal effect is confined to the
      inner 4 mm of the tumor wall. Here, we have studied whether temoporfin PDT (T
      PDT) shows an efficient local response and an increased tumoricidal penetration
      depth. In the first stage of a phase-II trial (NCT01016002), eleven patients with
      hBDC (Bismuth III-IV) were treated with T-PDT plus stenting and 10 could be
      analyzed for local tumor response. T-PDT resulted in complete local response in n
      = 1 of 10 patients, partial response in n = 8 and no response in one patient
      (occluded right hepatic duct re-opened but positive for residual tumor cells) -
      indicating a tumoricidal efficacy of 90%. Four patients showed a tumoricidal
      depth of >=7.5 mm. Cholestasis and palliation improved in 8 patients with an
      overall median survival of 18 (4.4-32.0) months after the first T-PDT. Adverse
      events were phototoxic skin reaction (n = 4), cholangitis (n = 3), and liver
      abscess (n = 3). T-PDT doubles the depth of the local tumor-ablative effect of P
      PDT, is highly tumoricidal and is associated with similar rates of infectious
      complications and grade I and II skin phototoxicity.

PMID- 23558739
TI  - Application of 3-dimensional speckle tracking imaging to the assessment of right
      ventricular regional deformation.
AB  - BACKGROUND: The aim of this study was to carry out 3-dimensional speckle tracking
      imaging (3DSTI) of the right ventricle (RV) and evaluate RV regional wall
      deformation. METHODS AND RESULTS: 3DSTI of the RV was performed in 35 normal
      subjects, 8 patients with arrhythmogenic right ventricular cardiomyopathy, and 8
      patients with pulmonary arterial hypertension. Peak systolic area change ratio
      and regional contraction timing relative to global systolic time (time to peak
      strain/time to end-systole*100) were measured in each segment. Good-quality
      images were acquired of the inflow segment in 87%, apex in 87%, outflow in 57%,
      and septum in 94% of the 35 normal subjects. In normal subjects, peak systolic
      area change ratio of the inflow anterior wall was -41+/-14%; inflow inferior
      wall, -35+/-9%; apical anterior wall, -41+/-10%; apical inferior wall, -31+/-11%;
      outflow, -31+/-9%; and septum wall, -36+/-11%. Contraction timing of the apical
      anterior wall and septum wall were earlier than those of other segments. In
      patients with RV dysfunction, 3DSTI indicated low peak systolic area change ratio
      in the damaged area. CONCLUSIONS: RV 3DSTI indicated segmental heterogeneity in
      magnitude and timing of RV contraction. 3DSTI may be a promising modality for
      providing precise quantitative information on complex RV wall motion.

PMID- 23558740
TI  - Dynamic left ventricular dyssynchrony assessed on 3-dimensional speckle-tracking
      area strain during dobutamine stress has a negative impact on cardiovascular
      events in patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Left ventricular (LV) dyssynchrony is not a stable phenomenon, but
      rather, changes dynamically. Given that the prognostic impact of dynamic
      dyssynchrony has not yet been elucidated, the objective was to investigate the
      clinical impact of dynamic dyssynchrony on patients with dilated cardiomyopathy
      (DCM). METHODS AND RESULTS: Seventy DCM patients with ejection fraction 32+/-9%
      were retrospectively recruited, and 3-dimensional speckle-tracking area strain
      was used to measure both contractile reserve and changes in dyssynchrony during
      dobutamine stress. The standard deviation of time-to-peak area strain was adopted
      as the systolic dyssynchrony index. Event-free survival was then tracked over a
      13-month period. A >=7.55% increase in systolic dyssynchrony index during
      dobutamine stress (Deltasystolic dyssynchrony index) was the best predictor of
      cardiovascular events with 77% sensitivity and 88% specificity. Multivariate Cox
      analysis indicated that not only the absence of contractile reserve (Deltaglobal
      area strain <=21.1%: hazard ratio [HR], 15.29; P=0.01), but the presence of
      dynamic dyssynchrony (DeltaLV dyssynchrony >=7.55%: HR: 7.591; P=0.003) was an
      independent predictor of cardiovascular events. Importantly, absence of dynamic
      dyssynchrony and presence of contractile reserve were associated with the most
      favorable outcome (98%), whereas the reverse condition was associated with the
      worst outcome (20%, P<0.001). CONCLUSIONS: Dynamic dyssynchrony is a potential
      predictor of cardiovascular events in patients with DCM, while assessment of
      dynamic dyssynchrony in combination with contractile reserve may further improve
      prognostic risk stratification.

PMID- 23558741
TI  - Combined white matter imaging suggests myelination defects in visual processing
      regions in schizophrenia.
AB  - Diverse pathological changes occur in the white matter (WM) of patients with
      schizophrenia. Various microstructural alterations including a reduction in
      axonal number or diameter, reduced myelination, or poor coherence of fibers could
      account for these changes. Abnormal integrity of macromolecules such as myelin
      ('dysmyelination') can be studied by applying multiple modalities of WM imaging
      such as diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)
      in parallel. Using ultra-high field (7 Tesla) MTI in 17 clinically stable
      patients with schizophrenia and 20 controls, we evaluated the voxelwise
      distribution of macromolecular WM abnormalities. Patients had a significant
      reduction in magnetization transfer ratio (MTR) in WM adjacent to visual
      processing regions and inferior temporal cortex (Cohen's d=1.54). Among the
      regions showing MTR reduction, a concurrent reduction in fractional anisotropy
      (FA) occurs proximal to the lingual gyrus. Multiple regression analysis revealed
      that the degree of FA reduction in the putatively 'dysmyelinated' regions in
      patients predicted impaired processing speed (PS; beta=0.74; P=0.003), a core
      cognitive dysfunction in schizophrenia. In controls, MTR/FA in the occipito
      temporal regions were not associated with PS. Our findings suggest that
      dysmyelination in visual processing regions is present in patients with
      schizophrenia with greatest cognitive and functional impairment. Combined DTI/MTI
      deficits in the occipito-temporal region may be an important variable when
      considering potential treatment targets for improving cognitive function in
      schizophrenia. 

PMID- 23558742
TI  - The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote.
AB  - Read alignment is an ongoing challenge for the analysis of data from sequencing
      technologies. This article proposes an elegantly simple multi-seed strategy,
      called seed-and-vote, for mapping reads to a reference genome. The new strategy
      chooses the mapped genomic location for the read directly from the seeds. It uses
      a relatively large number of short seeds (called subreads) extracted from each
      read and allows all the seeds to vote on the optimal location. When the read
      length is <160 bp, overlapping subreads are used. More conventional alignment
      algorithms are then used to fill in detailed mismatch and indel information
      between the subreads that make up the winning voting block. The strategy is fast
      because the overall genomic location has already been chosen before the detailed
      alignment is done. It is sensitive because no individual subread is required to
      map exactly, nor are individual subreads constrained to map close by other
      subreads. It is accurate because the final location must be supported by several
      different subreads. The strategy extends easily to find exon junctions, by
      locating reads that contain sets of subreads mapping to different exons of the
      same gene. It scales up efficiently for longer reads.

PMID- 23558743
TI  - Human polymerase kappa uses a template-slippage deletion mechanism, but can
      realign the slipped strands to favour base substitution mutations over deletions.
AB  - Polymerases belonging to the DinB class of the Y-family translesion synthesis DNA
      polymerases have a preference for accurately and efficiently bypassing damaged
      guanosines. These DinB polymerases also generate single-base (-1) deletions at
      high frequencies with most occurring on repetitive 'deletion hotspot' sequences.
      Human DNA polymerase kappa (hPolkappa), the eukaryotic DinB homologue, displays
      an unusual efficiency for to extend from mispaired primer termini, either by
      extending directly from the mispair or by primer-template misalignment. This
      latter property explains how hPolkappa creates single-base deletions in non
      repetitive sequences, but does not address how deletions occur in repetitive
      deletion hotspots. Here, we show that hPolkappa uses a classical Streisinger
      template-slippage mechanism to generate -1 deletions in repetitive sequences, as
      do the bacterial and archaeal homologues. After the first nucleotide is added by
      template slippage, however, hPolkappa can efficiently realign the primer-template
      duplex before continuing DNA synthesis. Strand realignment results in a base
      substitution mutation, minimizing generation of more deleterious frameshift
      mutations. On non-repetitive sequences, we find that nucleotide misincorporation
      is slower if the incoming nucleotide can correctly basepair with the nucleotide
      immediately 5' to the templating base, thereby competing against the mispairing
      with the templating base.

PMID- 23558744
TI  - Differential binding of the related transcription factors Pho4 and Cbf1 can tune
      the sensitivity of promoters to different levels of an induction signal.
AB  - Transcription factors that belong to the same family typically have similar, but
      not identical, binding specificities. As such, they can be expected to compete
      differentially for binding to different variants of their binding sites. Pho4 is
      a yeast factor whose nuclear concentration is up-regulated in low phosphate,
      while the related factor, Cbf1, is constitutively expressed. We constructed 16
      GFP-reporter genes containing all palindromic variants of the motif NNCACGTGNN,
      and determined their activities at a range of phosphate concentrations. Pho4
      affinity did not explain expression data well except under fully induced
      conditions. However, reporter activity was quantitatively well explained under
      all conditions by a model in which Cbf1 itself has modest activating activity,
      and Pho4 and Cbf1 compete with one another. Chromatin immunoprecipitation and
      computational analyses of natural Pho4 target genes, along with the activities of
      the reporter constructs, indicates that genes differ in their sensitivity to
      intermediate induction signals in part because of differences in their affinity
      for Cbf1. The induction sensitivity of both natural Pho4 target genes and
      reporter genes was well explained only by a model that assumes a role for Cbf1 in
      remodeling chromatin. Our analyses highlight the importance of taking into
      account the activities of related transcription factors in explaining system-wide
      gene expression data.

PMID- 23558745
TI  - The monomeric GIY-YIG homing endonuclease I-BmoI uses a molecular anchor and a
      flexible tether to sequentially nick DNA.
AB  - The GIY-YIG nuclease domain is found within protein scaffolds that participate in
      diverse cellular pathways and contains a single active site that hydrolyzes DNA
      by a one-metal ion mechanism. GIY-YIG homing endonucleases (GIY-HEs) are two
      domain proteins with N-terminal GIY-YIG nuclease domains connected to C-terminal
      DNA-binding and they are thought to function as monomers. Using I-BmoI as a model
      GIY-HE, we test mechanisms by which the single active site is used to generate a
      double-strand break. We show that I-BmoI is partially disordered in the absence
      of substrate, and that the GIY-YIG domain alone has weak affinity for DNA.
      Significantly, we show that I-BmoI functions as a monomer at all steps of the
      reaction pathway and does not transiently dimerize or use sequential
      transesterification reactions to cleave substrate. Our results are consistent
      with the I-BmoI DNA-binding domain acting as a molecular anchor to tether the GIY
      YIG domain to substrate, permitting rotation of the GIY-YIG domain to
      sequentially nick each DNA strand. These data highlight the mechanistic
      differences between monomeric GIY-HEs and dimeric or tetrameric GIY-YIG
      restriction enzymes, and they have implications for the use of the GIY-YIG domain
      in genome-editing applications.

PMID- 23558746
TI  - Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl
      adenosine base modification of 25S rRNA in Saccharomyces cerevisiae.
AB  - The 25S rRNA of yeast contains several base modifications in the functionally
      important regions. The enzymes responsible for most of these base modifications
      remained unknown. Recently, we identified Rrp8 as a methyltransferase involved in
      m(1)A645 modification of 25S rRNA. Here, we discovered a previously
      uncharacterized gene YBR141C to be responsible for second m(1)A2142 modification
      of helix 65 of 25S rRNA. The gene was identified by reversed phase-HPLC screening
      of all deletion mutants of putative RNA methyltransferase and was confirmed by
      gene complementation and phenotypic characterization. Because of the function of
      its encoded protein, YBR141C was named BMT2 (base methyltransferase of 25S RNA).
      Helix 65 belongs to domain IV, which accounts for most of the intersubunit
      surface of the large subunit. The 3D structure prediction of Bmt2 supported it to
      be an Ado Met methyltransferase belonging to Rossmann fold superfamily. In
      addition, we demonstrated that the substitution of G180R in the S-adenosyl-L
      methionine-binding motif drastically reduces the catalytic function of the
      protein in vivo. Furthermore, we analysed the significance of m(1)A2142
      modification in ribosome synthesis and translation. Intriguingly, the loss of
      m(1)A2142 modification confers anisomycin and peroxide sensitivity to the cells.
      Our results underline the importance of RNA modifications in cellular physiology.

PMID- 23558747
TI  - Impaired in vivo binding of MeCP2 to chromatin in the absence of its DNA methyl
      binding domain.
AB  - MeCP2 is a methyl-CpG-binding protein that is a main component of brain chromatin
      in vertebrates. In vitro studies have determined that in addition to its specific
      methyl-CpG-binding domain (MBD) MeCP2 also has several chromatin association
      domains. However, the specific interactions of MeCP2 with methylated or non
      methylated chromatin regions and the structural characteristics of the resulting
      DNA associations in vivo remain poorly understood. We analysed the role of the
      MBD in MeCP2-chromatin associations in vivo using an MeCP2 mutant Rett syndrome
      mouse model (Mecp2(tm1.1Jae)) in which exon 3 deletion results in an N-terminal
      truncation of the protein, including most of the MBD. Our results show that in
      mutant mice, the truncated form of MeCP2 (DeltaMeCP2) is expressed in different
      regions of the brain and liver, albeit at 50% of its wild-type (wt) counterpart.
      In contrast to the punctate nuclear distribution characteristic of wt MeCP2,
      DeltaMeCP2 exhibits both diffuse nuclear localization and a substantial retention
      in the cytoplasm, suggesting a dysfunction of nuclear transport. In mutant brain
      tissue, neuronal nuclei are smaller, and DeltaMeCP2 chromatin is digested faster
      by nucleases, producing a characteristic nuclease-resistant dinucleosome.
      Although a fraction of DeltaMeCP2 is found associated with nucleosomes, its
      interaction with chromatin is transient and weak. Thus, our results unequivocally
      demonstrate that in vivo the MBD of MeCP2 together with its adjacent region in
      the N-terminal domain are critical for the proper interaction of the protein with
      chromatin, which cannot be replaced by any other of its protein domains.

PMID- 23558748
TI  - Re-engineering an alphoid(tetO)-HAC-based vector to enable high-throughput
      analyses of gene function.
AB  - Human artificial chromosome (HAC)-based vectors represent an alternative
      technology for gene delivery and expression with a potential to overcome the
      problems caused by the use of viral-based vectors. The recently developed
      alphoid(tetO)-HAC has an advantage over other HAC vectors because it can be
      easily eliminated from cells by inactivation of the HAC kinetochore via binding
      of tTS chromatin modifiers to its centromeric tetO sequences. This provides
      unique control for phenotypes induced by genes loaded into the alphoid(tetO)-HAC.
      However, inactivation of the HAC kinetochore requires transfection of cells by a
      retrovirus vector, a step that is potentially mutagenic. Here, we describe an
      approach to re-engineering the alphoid(tetO)-HAC that allows verification of
      phenotypic changes attributed to expression of genes from the HAC without a
      transfection step. In the new HAC vector, a tTS-EYFP cassette is inserted into a
      gene-loading site along with a gene of interest. Expression of the tTS generates
      a self-regulating fluctuating heterochromatin on the alphoid(tetO)-HAC that
      induces fast silencing of the genes on the HAC without significant effects on HAC
      segregation. This silencing of the HAC-encoded genes can be readily recovered by
      adding doxycycline. The newly modified alphoid(tetO)-HAC-based system has
      multiple applications in gene function studies.

PMID- 23558749
TI  - LncRNA loc285194 is a p53-regulated tumor suppressor.
AB  - Protein-coding genes account for only a small part of the human genome, whereas
      the vast majority of transcripts make up the non-coding RNAs including long non
      coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a
      critical role in regulation of cellular processes such as cell growth and
      apoptosis as well as cancer progression and metastasis. LncRNA loc285194 was
      previously shown to be within a tumor suppressor unit in osteosarcoma and to
      suppress tumor cell growth. However, it is unknown regarding the regulation of
      loc285194. Moreover, the underlying mechanism by which loc285194 functions as a
      potential tumor suppressor is elusive. In this study, we show that loc285194 is a
      p53 transcription target; ectopic expression of loc285194 inhibits tumor cell
      growth both in vitro and in vivo. Through deletion analysis, we identify an
      active region responsible for tumor cell growth inhibition within exon 4, which
      harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth
      inhibition is in part due to specific suppression of miR-211. We further
      demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to
      loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of
      loc285194 in colon cancer specimens by quantitative PCR arrays and in situ
      hybridization of tissue microarrays. Together, these results suggest that
      loc285194 is a p53-regulated tumor suppressor, which acts in part through
      repression of miR-211.

PMID- 23558750
TI  - Probabilistic error correction for RNA sequencing.
AB  - Sequencing of RNAs (RNA-Seq) has revolutionized the field of transcriptomics, but
      the reads obtained often contain errors. Read error correction can have a large
      impact on our ability to accurately assemble transcripts. This is especially true
      for de novo transcriptome analysis, where a reference genome is not available.
      Current read error correction methods, developed for DNA sequence data, cannot
      handle the overlapping effects of non-uniform abundance, polymorphisms and
      alternative splicing. Here we present SEquencing Error CorrEction in Rna-seq data
      (SEECER), a hidden Markov Model (HMM)-based method, which is the first to
      successfully address these problems. SEECER efficiently learns hundreds of
      thousands of HMMs and uses these to correct sequencing errors. Using human RNA
      Seq data, we show that SEECER greatly improves on previous methods in terms of
      quality of read alignment to the genome and assembly accuracy. To illustrate the
      usefulness of SEECER for de novo transcriptome studies, we generated new RNA-Seq
      data to study the development of the sea cucumber Parastichopus parvimensis. Our
      corrected assembled transcripts shed new light on two important stages in sea
      cucumber development. Comparison of the assembled transcripts to known
      transcripts in other species has also revealed novel transcripts that are unique
      to sea cucumber, some of which we have experimentally validated. Supporting
      website: http://sb.cs.cmu.edu/seecer/.

PMID- 23558751
TI  - Rab GTPases-cargo direct interactions: fine modulators of intracellular
      trafficking.
AB  - Rab proteins are a large family of monomeric GTPases that comprise about 70
      members. These proteins cycle from a GDP-bound to a GTP-bound state and are
      considered molecular switches of membrane traffic. Indeed, they control several
      steps of vesicular trafficking such as vesicle formation, vesicle movement on
      actin and tubulin cytoskeletal tracks, vesicle tethering, docking and fusion to
      the target compartment. Accordingly, Rab proteins are considered key factors in
      vesicular trafficking as they have a fundamental role in specifying identity and
      routing of vesicles and organelles. Given their role in membrane traffic, it is
      not surprising that Rab proteins control the cellular fate of several membrane
      molecules such as signal transduction receptors and ion channels, being thus
      fundamental for their correct function. However, much evidence of interaction of
      a number of Rab proteins with cargo has been reported, raising the question of
      the functional meaning of these interactions. Indeed, Rab proteins have been
      demonstrated to directly interact with several membrane proteins, such as
      signaling receptors, immunoglobulin receptors, integrins and ion channels.
      Growing evidence indicates that, through interactions with Rab proteins, cargos
      directly control their own fate. Furthermore, often a cargo protein has the
      ability to interact with more than one Rab and/or with the same Rab in different
      activation states. This review focuses on these interactions highlighting their
      role in modulating cargo's trafficking and functions.

PMID- 23558752
TI  - Hallmarks of mechanochemistry: from nanoparticles to technology.
AB  - The aim of this review article on recent developments of mechanochemistry
      (nowadays established as a part of chemistry) is to provide a comprehensive
      overview of advances achieved in the field of atomistic processes, phase
      transformations, simple and multicomponent nanosystems and peculiarities of
      mechanochemical reactions. Industrial aspects with successful penetration into
      fields like materials engineering, heterogeneous catalysis and extractive
      metallurgy are also reviewed. The hallmarks of mechanochemistry include
      influencing reactivity of solids by the presence of solid-state defects,
      interphases and relaxation phenomena, enabling processes to take place under non
      equilibrium conditions, creating a well-crystallized core of nanoparticles with
      disordered near-surface shell regions and performing simple dry time-convenient
      one-step syntheses. Underlying these hallmarks are technological consequences
      like preparing new nanomaterials with the desired properties or producing these
      materials in a reproducible way with high yield and under simple and easy
      operating conditions. The last but not least hallmark is enabling work under
      environmentally friendly and essentially waste-free conditions (822 references). 

PMID- 23558754
TI  - Systematic review of the psychometric properties of the questionnaire to evaluate
      the adherence to HIV therapy (CEAT-VIH).
AB  - BACKGROUND: Since the use of the questionnaire to evaluate adherence to HIV
      therapy (acronym CEAT-VIH) has increased in the last decade and translation into
      new language versions has been requested, summarizing information regarding the
      psychometric properties of the instrument may be useful for researchers and
      practitioners. OBJECTIVE: The purpose of this work was to review the psychometric
      properties of the questionnaire CEAT-VIH, available from published studies and
      research reports. DATA SOURCES: Medline, PsycINFO, Google Scholar and Google; the
      searched period was from 2001 to 2012. STUDY SELECTION: Forty-eight research
      materials referring to the questionnaire CEAT-VIH were initially gathered from
      academic databases and direct contact with researchers, before being analyzed.
      From the initial pool of material compiled (i.e., abstracts, technical reports or
      database files, dissertations or complete articles), only 20 comprised original
      data. STUDY APPRAISAL AND SYNTHESIS METHODS: The selected research material
      described a variety of information in terms of the psychometric properties of the
      questionnaire. The results from the primary studies were then summarized in
      tables for evaluation, description and comparison. RESULTS: Thirteen out of 16
      studies reported a Cronbach's alpha value of above 0.70, supporting the internal
      consistency reliability of the CEAT-VIH questionnaire. No floor or ceiling
      effects were observed. Hypothesized relationships between the CEAT-VIH score and
      adherence-related variables (e.g., viral load, CD4+, compliance evaluated by
      physician or pharmacist, complexity of treatment and pill numbers) were observed,
      indicating validity evidence. Thus, variables expected to act as psychological
      risk factors for low adherence (e.g., stress, depression and anxiety) or
      protector factor (e.g., social support) to good adherence were observed. The
      scores of the questionnaire were also related to quality of life outcomes.
      Moreover, patients that received adherence intervention showed increased CEAT-VIH
      adherence scores. Sensitivity and specificity to correctly identify adherent
      patients with undetectable viral load were also observed for three studies.
      LIMITATIONS: Although the data provided in the reports were heterogeneous, these
      were valuable and reported enough evidence of validity for the instrument. The
      selected studies represented 41.7 % of those initially identified, and only eight
      out of 20 documents were peer reviewed. CONCLUSIONS: The CEAT-VIH has been used
      for a variety of individuals of different ages, sex, socioeconomic and
      educational backgrounds. It has been a reliable and valid tool in measuring
      adherence to HIV treatment among different samples, and has been used with a wide
      range of study populations and countries (i.e., Brazil, Chile, Colombia, Mexico,
      Panama, Peru, Portugal, Puerto Rico, Romania and Spain). Encouraging data
      reported here may allow the recommendation of the CEAT-VIH as a valuable measure
      to use in HIV adherence research, especially in countries where the questionnaire
      already has available psychometric evidence.

PMID- 23558755
TI  - The joint relationship between organizational design factors and HR practice
      factors on direct care workers' job satisfaction and turnover intent.
AB  - BACKGROUND: Human resource (HR) practices, such as training and communication,
      have been linked to positive employee job commitment and lower turnover intent
      for direct care workers (DCWs). Not many studies have looked at the combined
      interaction of HR practices and organizational structure. PURPOSE: The aim of
      this study is to examine the relationship between organizational structure
      (centralization, formalization, and span of control) and HR practices (training,
      horizontal communication, and vertical communication) on DCW's job satisfaction
      and turnover intent. METHODOLOGY: Data were collected from 58 long-term care
      facilities in five states. We used latent class analysis to group facility
      characteristics into three sets of combinations: "organic," "mechanistic," and
      "minimalist." We used multivariate regression to test the relationship of each of
      these groups on DCW's job satisfaction and turnover intent. FINDINGS: After
      controlling for state, organizational, and individual covariates, the organic
      group, which represents decentralized and less formalized structures and high
      levels of job training and communication, was positively related to job
      satisfaction and negatively related to intent to leave. On the other hand, the
      minimalist group, which is characterized by low levels of job-related training
      and communication, showed no significant differences from the mechanistic group
      (referent) on job satisfaction and intent to leave. PRACTICE IMPLICATIONS: These
      findings imply that managers in long-term care facilities may want to consider
      adopting organic, decentralized structures and HR practices to retain DCWs.

PMID- 23558756
TI  - A new method to detect air leakage in a patient with pneumothorax using saline
      solution and multidetector-row spiral CT scan.
AB  - BACKGROUND: The purpose of this study was to establish a new CT scan method to
      show signs of air leakage and to detect the point of the lung leak in patients
      with spontaneous pneumothorax by using saline solution and phonation. METHODS:
      Eleven patients with spontaneous pneumothorax who had a chest tube placed and
      underwent an operation because of continuing air leakage were studied. After a
      plain chest CT scan was performed, 0.9% saline was injected into the affected
      pleural cavity. A CT scan was acquired again while the patient vocalized
      continuously. The CT images were evaluated by two thoracic surgeons. All patients
      underwent video-assisted thoracoscopic surgery to confirm their points of leakage
      and were treated for spontaneous pneumothorax. RESULTS: Bubble shadows were seen
      in nine of 11 cases. In seven of those nine cases, multiple bubbles formed foam
      or wave shadows. These cases had a small pleural fistula. In the other two cases
      with a large fistula, air-fluid level in bulla and ground-glass attenuation areas
      were seen in the pulmonary parenchyma. In all 11 cases, some air-leakage signs
      were seen on CT scan, and a culprit lesion was presumed to exist by analyzing CT
      imaging findings and confirming with a surgical air-leak test. CONCLUSIONS: With
      a saline injection and vocalization, CT scan could demonstrate air-leak signs in
      patients with spontaneous pneumothorax. This method does not require contrast
      medium, special instruments, or high skill and, thus, is a novel and useful
      examination to detect the culprit lesion in pneumothorax.

PMID- 23558757
TI  - Diastereoselective synthesis of meso-pillar[6]arenes by bridging between
      hydroquinone units in an alternating up-and-down manner.
AB  - We report the first synthesis of bridged pillararenes. Meso-form pillar[6]arenes
      were diastereo-selectively formed by bridging units of a per-hydroxylated
      pillar[6]arene in an alternating up-and-down manner with dialkyldichlorosilanes.

PMID- 23558758
TI  - Three-dimensional metabolic and radiologic gathered evaluation using VR-RENDER
      fusion: a novel tool to enhance accuracy in the localization of parathyroid
      adenomas.
AB  - BACKGROUND: The aim of this study was to assess the accuracy of a novel imaging
      modality, three-dimensional (3D) metabolic and radiologic gathered evaluation
      (MeRGE), for localizing parathyroid adenomas (PAs). METHODS: Consecutive patients
      presenting with primary hyperparathyroidism who underwent both thin-slice
      cervical computed tomography (CT) and (99m)Tc-sestamibi (MIBI) scanning were
      included. 3D-CT reconstruction was obtained using VR-RENDER, which was used to
      perform 3D virtual neck exploration (3D-VNE). The MIBI scan was then fused with
      the 3D reconstruction to obtain 3D-MeRGE. Sensitivity, specificity, and accuracy
      were assessed. Parathyroid gland volume and preoperative parathormone (PTH)
      levels were analyzed as predictive factors of correct localization (i.e., correct
      quadrant). RESULTS: A total of 108 cervical quadrants (27 patients) were
      analyzed. Sensitivities were 79.31, 75.86, 65.51, and 58.61 % with 3D-MeRGE, 3D
      VNE, MIBI, and CT, respectively. Specificity was highest with CT (94.93 %)
      followed by 3D-VNE (92.4 %). MIBI and 3D-MeRGE had the same specificity (88.6 %).
      3D-MeRGE and 3D-VNE achieved higher accuracy than MIBI or CT alone. Mean PTH
      values were significantly higher in patients with lesions that were correctly
      identified (true positive, TP) than in those whose lesions were missed (false
      negative, FN) with 3D-VNE (219.60 +/- 212.77 vs. 98.75 +/- 12.76 pg/ml; p = 0.01)
      and 3D-MeRGE (217.69 +/- 213.76 vs. 09.75 +/- 20.48 pg/ml; p = 0.02). The mean
      parathyroid gland volume difference between TP and FN was statistically
      significant with all modalities except CT. CONCLUSIONS: 3D-MeRGE and 3D-VNE
      showed high accuracy for localization of PAs. 3D-MeRGE performed better than MIBI
      or CT alone for detecting small adenomas and those with a low PTH level.

PMID- 23558759
TI  - Bilateral axillo-breast approach robotic thyroidectomy for Graves' disease: an
      initial experience in a single institute.
AB  - BACKGROUND: Bilateral axillo-breast approach (BABA) robotic thyroidectomy has
      shown excellent cosmetic and surgical outcomes. The aim of the present study was
      to evaluate the safety, feasibility, and initial outcome of this procedure in
      patients with Graves' disease. METHODS: From June 2008 to July 2001, a total of
      30 patients with Graves' disease were reviewed retrospectively. Patient
      demographics, operative indications, and surgical variables, including operative
      time, blood loss, excised thyroid weight, and complications, were collected and
      investigated. RESULTS: The thyroidectomies were classified as total (n = 21),
      near-total (n = 6), or subtotal (n = 3). There were five indications for surgery:
      concomitant thyroid carcinoma or suspicious nodule (n = 22), recurrence after
      antithyroid medication (n = 2), local compressive symptoms (n = 1), patient's
      preference (n = 4), and side effects of antithyroid medication (n = 1). The mean
      operative time, console time, blood loss, and excised thyroid weight were 190 min
      (range: 105-298 min), 113 min (range: 60-227 min), 229 mL (range: 50-550 mL), and
      36.6 g (range: 7.8-123.0 g), respectively. There were no cases of postoperative
      bleeding or conversions to open surgery. Postoperative transient
      hypoparathyroidism and vocal cord palsy occurred in 13 (43.3 %) and 4 (13.3 %)
      cases. Permanent hypoparathyroidism occurred in 1 (3.3 %) case. All patients were
      satisfied with the cosmetic outcomes. CONCLUSIONS: BABA robotic thyroidectomy is
      a feasible and safe treatment for Graves' disease. It is recommended as an
      alternative for patients who are concerned by the cosmetic effects of traditional
      thyroidectomy.

PMID- 23558760
TI  - Safety and efficacy of transdermal buprenorphine and transdermal fentanyl in the
      treatment of neuropathic pain in AIDS patients.
AB  - BACKGROUND: Multifactor neuropathic pain is one of the most frequent symptoms in
      AIDS patients and analgesic treatment is primarily based on the use of drug
      combination of opioids, tricyclic antidepressants and antiepileptics. However,
      the chronic use of opioids in AIDS patients presents a risk due to the
      immunosuppressive action of these drugs. Until now, buprenorphine has been
      regarded as one of the safest opioid analgesics for the treatment of patients
      with compromised immune systems. To assess the suitability of transdermal
      fentanyl for the treatment of neuropathic pain in AIDS patients, the present
      study compares the efficacy, tolerability and the immunosuppressive effects of
      transdermal buprenorphine vs. fentanyl. METHODS: Forty advanced AIDS patients (28
      male and 12 female) with chronic peripheral neuropathic pain were enrolled onto
      this clinical trial. Neuropathic pain was assessed for its constituent types of
      pain (burning, stabbing and shooting), its overall intensity and allodynia;
      scores were awarded using the Neuropathic Pain Scale, expressed as 10 item VAS
      scores. RESULTS: Both treatment groups showed statistically significant
      reductions in each of the individual types of neuropathic pain and allodynia
      (P<0.05; 95% CI: -14.7, -3.1) and significant improvements in Karnofsky
      Performance Status (P<0.05; mean value, 69; range: 40-90). Both buprenorphine and
      fentanyl were well tolerated. Neither buprenorphine nor fentanyl affected CD4+ or
      CD8+levels and both treatments, but particularly buprenorphine group, resulted in
      more stable CD4+ concentrations. CONCLUSION: The high efficacy, tolerability and
      patient compliance of both buprenorphine and fentanyl make both these two opioids
      valid therapeutic options for the treatment of neuropathic pain in patients with
      AIDS.

PMID- 23558761
TI  - Identifying clinical and acute psychological risk factors for PTSD after critical
      care: a systematic review.
AB  - BACKGROUND: Patients may suffer extreme psychological reactions in intensive care
      units (ICU), and post-traumatic stress disorder (PTSD) after leaving hospital.
      Previous systematic reviews of studies up to 2007 found that the true prevalence
      of and consistent risk factors for PTSD after ICU were not established, due to
      methodological shortcomings of studies. Therefore we aimed to conduct a
      systematic review of observational studies of post-ICU PTSD from 2008-2012, and
      to compare them to 1997-2007 studies, with regard to quality, prevalence
      estimates and risk factors. METHODS: We used a pre-specified protocol, and
      systematic, explicit methods to identify, select and critically appraise studies.
      Studies in general ICU settings with mixed-diagnosis patients (N.>30) were
      included. Risk of bias was assessed, with lower-risk studies given greater
      weight. No quantitative synthesis was possible due to heterogeneity, therefore
      ranges of estimates and frequencies of risk factors were examined. RESULTS: The
      review included 26 papers, 13 from 1997-2007 and 13 from 2008-2012. There were
      more high quality studies in the latter period. The range of prevalence estimates
      from high-quality studies was similar; 8% to 27% (1997-2007) and 9% to 27% (2008
      2012). Clinical risk factors consistently identified over the two periods were
      use of benzodiazepines, duration of sedation and mechanical ventilation.
      Psychological risk factors include stress and fear experienced acutely in ICU,
      and frightening memories of the admission. CONCLUSION: The quality and number of
      post-ICU PTSD studies has increased over time, and we can be more confident in
      the accumulated findings. Evidence from both periods suggests that up to 27% of
      ICU survivors suffer from PTSD. There is also increasing evidence that use of
      benzodiazepines and duration of sedation, along with fear, stress and delirium in
      the ICU are likely risk factors for subsequent PTSD.

PMID- 23558762
TI  - Trends in opioid analgesics sales to community pharmacies and hospitals in Italy
      (2000-2010).
AB  - BACKGROUND: Opioid consumption data in Italy have been widely studied. However,
      only aggregate data can be found in the published literature, and differences are
      expected by distribution setting (community pharmacies and hospitals). The aim of
      our paper is to analyse opioids sales trends in Italy in the decade 2000-2010, in
      an effort to explore such differences. METHODS: Quarterly sales data of opioid
      medicinal products sold by wholesalers to both community pharmacies (retail) and
      to hospitals (non-retail) during the time period 2000-2010 were supplied by IMS
      Italy. Data were standardized using the Defined Daily Doses per day per 1000
      inhabitants (DDDd/1000). RESULTS: Opioid sales have steadily increased during the
      time period considered going from 1.04 DDDd/1000 in 2000 to 4.9 in 2010 (+292%).
      Nonetheless relevant differences can be found both by distribution setting and
      drug type. In particular retail sales have increased by 286 % for WHO Step II
      opioids and by 575% for WHO Step III drugs, while non-retail sales have increased
      by 48% and 263%, respectively. In 2010, fentanyl and buprenorphine transdermal
      patches and oxycodone are more widely prescribed than morphine, in the retail
      setting, with fentanyl at large in the first position. In hospitals morphine and
      fentanyl almost equally share the 75% of the market. CONCLUSION: Data suggest
      that morphine is no more the opioid of first choice for severe pain in Italy, at
      least for outpatients. This is contradicting most international guidelines
      available in the 2000-2010 decade.

PMID- 23558763
TI  - Neurally adjusted ventilatory assist in non-invasive ventilation.
AB  - This manuscript describes the motivation for developing neurally adjusted
      ventilatory assist (NAVA) and its subsequent use with a non-invasive interface.
      The challenges with conventional, pneumatically controlled non-invasive modes are
      briefly described, followed by a mini-review on the upper airways and the
      diaphragm electrical activity (EAdi) signal. The bulk of the review focuses on
      the importance and use of monitoring the EAdi during non-invasive ventilation,
      and a report of the recent experimental and clinical findings with NAVA during
      non-invasive ventilation. In summary, non-invasive NAVA provides a truly
      synchronized mode of non-invasive ventilation, both in time and in level of
      assist. Along with EAdi monitoring, NAVA can increase the confidence to treat
      respiratory failure non-invasively. 

PMID- 23558764
TI  - An intubation tube whose distal end was covered with the cuff of tube.

PMID- 23558765
TI  - Performance of different PEEP valves and helmet outlets at increasing gas flow
      rates: a bench top study. Authors reply.

PMID- 23558766
TI  - Pediatric enoxaparin overdose: more attention to thromboelastography monitoring.

PMID- 23558767
TI  - Oxygen instead of Blood - Not in too sick or too low.

PMID- 23558768
TI  - A biomarker panel: an additional resource in acute stroke evaluation?

PMID- 23558769
TI  - CO2 insufflations during laparoscopic surgery: the paradox of oxygenation.

PMID- 23558770
TI  - Effect of the site of assisted hatching on vitrified-warmed blastocyst transfer
      cycles: a prospective randomized study.
AB  - PURPOSE: To assess the effect of assisted hatching (AH) site on the clinical
      outcomes in vitrified-warmed blastocyst transfer cycles. METHODS: A total of 160
      women who underwent vitrified-warmed blastocyst transfer cycles were randomized
      to either the ICM group (AH performing at the site near the inner cell mess,
      ICM), or the TE group (AH performing at the site opposite to the ICM). AH with
      laser zona drilling was performed 20 or 30 min after thawing once the ICM can be
      detected. Clinical pregnancy rate, implantation rate, live birth rate and the
      occurrence rate of monozygotic twins (MZT) pregnancy after transfer of these two
      groups were compared. RESULTS: No significant difference was found in the
      clinical pregnancy rate (63.8% vs. 67.5%), implantation rate (51.7% vs. 53.6%)
      and live birth rate (57.5% vs. 62.5%) between the ICM group and the TE group. The
      occurrence rate of MZT was comparable between the two groups (3.9% vs. 5.6%).
      CONCLUSIONS: The site of assisted hatching has no influence on the implantation,
      pregnancy and live birth rate in human vitrified-warmed blastocyst transfer
      cycles.

PMID- 23558771
TI  - Platelet-rich plasma limits the nerve injury caused by 10% dextrose in the rabbit
      median nerve.
AB  - INTRODUCTION: We evaluated the effect of platelet-rich plasma (PRP) injection in
      a rabbit model of dextrose-induced median nerve injury. METHODS: New Zealand
      white rabbits (n = 15) were divided randomly into 3 groups. Three different
      regimens (group 1: 0.1 ml saline; group 2: 10% dextrose with PRP; group 3: 10%
      dextrose with saline) were injected within the carpal tunnel.
      Electrophysiological and histological findings were evaluated 12 weeks after the
      injection. RESULTS: The mean median motor latency in group 3 was significantly
      longer than that in groups 1 and 2. The cross-sectional area of the median nerve
      and subsynovial connective tissue thickness in group 3 were significantly larger
      than those in groups 1 and 2. CONCLUSIONS: PRP injection may be effective in
      controlling median nerve injury, as demonstrated by improvement in
      electrophysiological and histological findings 12 weeks after dextrose injection.

PMID- 23558772
TI  - Control of myogenesis by rodent SINE-containing lncRNAs.
AB  - Staufen1-mediated mRNA decay (SMD) degrades mRNAs that harbor a Staufen1-binding
      site (SBS) in their 3' untranslated regions (UTRs). Human SBSs can form by
      intermolecular base-pairing between a 3' UTR Alu element and an Alu element
      within a long noncoding RNA (lncRNA) called a &frac12;-sbsRNA. Since Alu elements
      are confined to primates, it was unclear how SMD occurs in rodents. Here we
      identify mouse mRNA 3' UTRs and lncRNAs that contain a B1, B2, B4, or identifier
      (ID) element. We show that SMD occurs in mouse cells via mRNA-lncRNA base-pairing
      of partially complementary elements and that mouse &frac12;-sbsRNA (m&frac12;
      sbsRNA)-triggered SMD regulates C2C12 cell myogenesis. Our findings define new
      roles for lncRNAs as well as B and ID short interspersed elements (SINEs) in mice
      that undoubtedly influence many developmental and homeostatic pathways.

PMID- 23558773
TI  - Peregrine: A rapid and unbiased method to produce strand-specific RNA-Seq
      libraries from small quantities of starting material.
AB  - Use of second generation sequencing (SGS) technologies for transcriptional
      profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of
      RNA abundances with unprecedented specificity and sensitivity and the discovery
      of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the
      RNA starting material into cDNA flanked by platform-specific adaptor sequences.
      Each of the published methods and commercial kits currently available for RNA-Seq
      library preparation suffers from at least one major drawback, including long
      processing times, large starting material requirements, uneven coverage, loss of
      strand information and high cost. We report the development of a new RNA-Seq
      library preparation technique that produces representative, strand-specific RNA
      Seq libraries from small amounts of starting material in a fast, simple and cost
      effective manner. Additionally, we have developed a new quantitative PCR-based
      assay for precisely determining the number of PCR cycles to perform for optimal
      enrichment of the final library, a key step in all SGS library preparation
      workflows.

PMID- 23558774
TI  - Gun violence is a health crisis: physicians' responsibilities.

PMID- 23558775
TI  - Pharmaceutical sales representatives and patient safety: a comparative
      prospective study of information quality in Canada, France and the United States.
AB  - INTRODUCTION: The information provided by pharmaceutical sales representatives
      has been shown to influence prescribing. To enable safe prescribing, medicines
      information must include harm as well as benefits. Regulation supports this aim,
      but relative effectiveness of different approaches is not known. The United
      States (US) and France directly regulate drug promotion; Canada relies on
      industry self-regulation. France has the strictest information standards.
      METHODS: This is a prospective cohort study in Montreal, Vancouver, Sacramento
      and Toulouse. We recruited random samples of primary care physicians from May
      2009 to June 2010 to report on consecutive sales visits. The primary outcome
      measure was "minimally adequate safety information" (mention of at least one
      indication, serious adverse event, common adverse event, and contraindication,
      and no unqualified safety claims or unapproved indications). RESULTS: Two hundred
      and fifty-five physicians reported on 1,692 drug-specific promotions. "Minimally
      adequate safety information" did not differ: 1.7 % of promotions; range 0.9-3.0 %
      per site. Sales representatives provided some vs. no information on harm more
      often in Toulouse than in Montreal and Vancouver: 61 % vs. 34 %, OR = 4.0; 95 %
      CI 2.8-5.6, or Sacramento (39 %), OR = 2.4; 95 % CI 1.7-3.6. Serious adverse
      events were rarely mentioned (5-6 % of promotions in all four sites), although 45
      % of promotions were for drugs with US Food and Drug Administration (FDA) "black
      box" warnings of serious risks. Nevertheless, physicians judged the quality of
      scientific information to be good or excellent in 901 (54 %) of promotions, and
      indicated readiness to prescribe 64 % of the time. DISCUSSION: "Minimally
      adequate safety information" did not differ in the US and Canadian sites, despite
      regulatory differences. In Toulouse, consistent with stricter standards, more
      harm information was provided. However, in all sites, physicians were rarely
      informed about serious adverse events, raising questions about whether current
      approaches to regulation of sales representatives adequately protect patient
      health.

PMID- 23558776
TI  - [Aortic aneurysms and aortic dissection: epidemiology, pathophysiology and
      diagnostics].
AB  - Aortic aneurysms and aortic dissection represent a significant health risk due to
      the demographic developments and current life styles. The mortality of ruptured
      aortic aneurysms is up to 80 % and the prevalence of aneurysms varies depending
      on the localization (thoracic or abdominal). Most commonly affected is the
      infrarenal abdominal aorta; however, there is evidence that the prevalence is
      diminishing but in contrast the incidence of thoracic aortic aneurysms is
      increasing. Aortic dissection is often fatal and is the most common acute aortic
      disease but the incidence is presumed to be underestimated. The pathogenesis of
      aortic aneurysms is manifold and is based on an interplay between degenerative,
      proteolytic and inflammatory processes. An aortic dissection arises from a tear
      in the intima which results in a separation of the aortic wall layers with
      infiltration of bleeding and the danger of aortic rupture. Various genetic
      disorders of connective tissue promote degeneration of the aortic media, most
      notably Marfan syndrome. Risk factors for aortic aneurysms and aortic dissection
      are nicotine abuse, arterial hypertension, age and male gender. Aortic aneurysms
      initially have an uneventful course and as a consequence are mostly discovered
      incidentally. The clinical course and symptoms of aortic dissection are very much
      dependent on the section of the aorta affected and the manifestations are
      manifold. Acute aortic dissection is in 80 % of cases first manifested as sudden
      extremely severe pain. The diagnostics and subsequent course control can be
      achieved by a variety of imaging procedures but the modality of choice is
      computed tomography.

PMID- 23558777
TI  - [Headache and transient aphasia in a 35-year-old female patient].
AB  - We describe the case of a 35-year-old female patient who suffered from fulminant
      tick-borne encephalitis and subsequently died. Remarkable about this case was
      that the woman was not living in an endemic area and that the disease occurred
      outside the usual season. Furthermore, this indicates that an increase in
      transmission of tick-borne encephalitis can be expected outside the classical
      endemic areas in higher altitudes, possibly as a consequence of climate changes.

PMID- 23558778
TI  - Aflatoxin B1 and zearalenone in dairy feeds in Portugal, 2009-2011.
AB  - This paper presents 3 years of data (2009-2011) on the occurrence of two
      mycotoxins, aflatoxin B1 (AFB1) and zearalenone (ZEA), in samples of feedstuff
      for dairy cows (n = 963), ewes (n = 42), and goats (n = 131) produced in
      Portugal. AFB1 was found in 15 samples of cow feed (1.6%), 3 samples of ewe feed
      (2.3%) and in 2 samples of goat feed (4.8%). All but two samples contained AFB1
      at levels below the European Union maximum level (5 MUg/kg). Nearly half (45%) of
      the samples were contaminated with ZEA, but its levels were relatively low, at 5
      136.9 MUg/kg, well below the European Union guidance value (500 MUg/kg).

PMID- 23558779
TI  - Catechol metabolites of the mycotoxin zearalenone are poor substrates but potent
      inhibitors of catechol-O-methyltransferase.
AB  - The mycotoxin zearalenone (ZEN) elicits estrogenic effects and is biotransformed
      to two catechol metabolites, in analogy to the endogenous steroidal estrogen
      17beta-estradiol (E2). Previous studies have shown that the catechol metabolites
      of ZEN have about the same potency to induce oxidative DNA damage as the catechol
      metabolites of E2, but are less efficiently converted to their methyl ethers by
      human hepatic catechol-O-methyltransferase (COMT). Here, we report that the two
      catechol metabolites of ZEN, i.e. 13-hydroxy-ZEN and 15-hydroxy-ZEN, are not only
      poor substrates of human COMT but are also able to strongly inhibit the O
      methylation of 2-hydroxy-E2, the major catechol metabolite of E2. 15-Hydroxy-ZEN
      acts as a non-competitive inhibitor and is about ten times more potent than 13
      hydroxy-ZEN, which is an uncompetitive inhibitor of COMT. The catechol
      metabolites of ZEN were also shown to inhibit the O-methylation of 2-hydroxy-E2
      by hepatic COMT from mouse, rat, steer and piglet, although to a lesser extent
      than observed with human COMT. The powerful inhibitory effect of catechol
      metabolites of ZEN on COMT may have implications for the tumorigenic activity of
      E2, because catechol metabolites of E2 elicit genotoxic effects, and their
      impaired O-methylation may increase the tumorigenicity of steroidal estrogens. 

PMID- 23558780
TI  - A facile route to steady redox-modulated nitroxide spin-labeled surfaces based on
      diazonium chemistry.
AB  - A TEMPO derivative was covalently grafted onto carbon and gold surfaces via the
      diazonium chemistry. The acid-dependent redox properties of the nitroxyl group
      were exploited to elaborate electro-switchable magnetic surfaces. ESR
      characterization demonstrated the reversible and permanent magnetic character of
      the material.

PMID- 23558781
TI  - Making medical decisions in dependence of genetic background: estimation of the
      utility of DNA testing in clinical, pharmaco-epidemiological or genetic studies.
AB  - An index measuring the utility of testing a DNA marker before deciding between
      two alternative treatments is proposed which can be estimated from pharmaco
      epidemiological case-control or cohort studies. In the case-control design,
      external estimates of the prevalence of the disease and of the frequency of the
      genetic risk variant are required for estimating the utility index. Formulas for
      point and interval estimates are derived. Empirical coverage probabilities of the
      confidence intervals were estimated under different scenarios of disease
      prevalence, prevalence of drug use, and population frequency of the genetic
      variant. To illustrate our method, we re-analyse pharmaco-epidemiological case
      control data on oral contraceptive intake and venous thrombosis in carriers and
      non-carriers of the factor V Leiden mutation. We also re-analyse cross-sectional
      data from the Framingham study on a gene-diet interaction between an APOA2
      polymorphism and high saturated fat intake on obesity. We conclude that the
      utility index may be helpful to evaluate and appraise the potential clinical and
      public health relevance of gene-environment interaction effects detected in
      genomic and candidate gene association studies and may be a valuable decision
      support for designing prospective studies on the clinical utility.

PMID- 23558782
TI  - VMP1 is a new player in the regulation of the autophagy-specific
      phosphatidylinositol 3-kinase complex activation.
AB  - We have elucidated a novel mechanism through which the autophagy-specific class
      III phosphatidylinositol 3-kinase (PtdIns3K) complex can be recruited to the PAS
      in mammalian cells, through the interaction between BECN1 and the vacuole
      membrane protein 1 (VMP1), an integral autophagosomal membrane protein. This
      interaction involves the binding between the C-terminal 20 amino acids of the
      VMP1 hydrophilic domain, which we have named the VMP1 autophagy-related domain
      (VMP1-AtgD), and the BH3 domain of BECN1. The association between these two
      proteins allows the formation of the autophagy-specific PtdIns3K complex, which
      activity favors the generation of phosphatidylinositol-3-phosphate (PtdIns3P) and
      the subsequent association of the autophagy-related (ATG) proteins, including
      ATG16L1, with the phagophore membranes. Therefore, VMP1 regulates the PtdIns3K
      activity on the phagophore membrane through its interaction with BECN1. Our data
      provide a novel model describing one of the key steps in phagophore assembly site
      (PAS) formation and autophagy regulation, and positions VMP1 as a new interactor
      of the autophagy-specific PtdIns3K complex in mammalian cells.

PMID- 23558783
TI  - Disposable polymeric cryogel bioreactor matrix for therapeutic protein
      production.
AB  - Low cost and high efficiency make disposable bioreactors feasible for small-scale
      therapeutic development and initial clinical trials. We have developed a cryogel
      based disposable bioreactor matrix, which has been used for production of protein
      therapeutics such as urokinase and monoclonal antibodies (mAbs). The protocol
      discusses the application of a cryogel bioreactor for mAb production. Cryogels
      composed of either polyacrylamide (PAAm) coupled to gelatin or semi
      interpenetrating PAAm-chitosan are synthesized by free-radical polymerization at 
      12  degrees C. Hybridoma cells are immobilized over the cryogel bioreactor and
      incubated for 48 h. Medium is circulated thereafter at 0.2 ml min(-1) and
      bioreactors can be run continuously for 60 d. The cryogel-based packed-bed
      bioreactor can be formulated as a monolith or as beads; it also has an efficiency
      four times what can be obtained using a tissue-culture flask, a high surface-to
      volume ratio and effective nutrient transport. After incubation, the bioreactor
      setup will take about 60 min using a pre-prepared sterilized cryogel.

PMID- 23558784
TI  - A preclinical xenograft model of prostate cancer using human tumors.
AB  - Most cases of prostate cancer are now diagnosed as moderate-grade localized
      disease. These tumor specimens are important tools in the discovery and
      translation of prostate cancer research; however, unlike more advanced tumors,
      they are notoriously difficult to grow in the laboratory. We developed a system
      for efficiently xenografting localized human prostate cancer tissue, and we
      adapted this protocol to study the interactions between the specific subsets of
      epithelial and stromal cells. Fresh prostate tissues or isolated epithelial cells
      are recombined with mouse seminal vesicle mesenchyme (SVM) and grafted under the
      renal capsule of immunodeficient mice for optimum growth and survival.
      Alternatively, mouse mesenchyme can be replaced with human prostate fibroblasts
      in order to determine their contribution to tumor progression. Grafts can be
      grown for several months to determine the effectiveness of novel therapeutic
      compounds when administered to host mice, thereby paving the way for
      personalizing the treatment of individual prostate cancers.

PMID- 23558785
TI  - Genome-wide mapping of RNA structure using nuclease digestion and high-throughput
      sequencing.
AB  - RNA structure is important for RNA function and regulation, and there is growing
      interest in determining the RNA structure of many transcripts. Here we provide a
      detailed protocol for the parallel analysis of RNA structure (PARS) for probing
      RNA secondary structures genome-wide. In this method, enzymatic footprinting is
      coupled to high-throughput sequencing to provide secondary structure data for
      thousands of RNAs simultaneously. The entire experimental protocol takes ~5 d to
      complete, and sequencing and data analysis take an additional 6-8 d. PARS was
      developed using the yeast genome as proof of principle, but its approach should
      be applicable to probing RNA structures from different transcriptomes and
      structural dynamics under diverse solution conditions.

PMID- 23558787
TI  - Light-induced tryptophan radical generation in a click modular assembly of a
      sensitiser-tryptophan residue.
AB  - Click chemistry was used as an efficient method to covalently attach a
      chromophore to an amino acid. Such easily prepared model systems allow for time
      resolved studies of one-electron oxidation reactions by the excitation of the
      chromophore by a laser flash. The model complex ruthenium-tryptophan (Ru-Trp) has
      been synthesised and studied for its photophysical and electrochemical
      properties. Despite a small driving force of less than 100 meV, excitation with a
      laser flash results in fast internal electron transfer leading to the formation
      of the protonated radical (TrpH(+)). At neutral pH electron transfer is followed
      by deprotonation to form the neutral Trp radical with the rate depending on the
      concentration of water acting as the proton acceptor. The formation of the
      tryptophan radical was confirmed by EPR.

PMID- 23558786
TI  - Single-cell analysis and sorting using droplet-based microfluidics.
AB  - We present a droplet-based microfluidics protocol for high-throughput analysis
      and sorting of single cells. Compartmentalization of single cells in droplets
      enables the analysis of proteins released from or secreted by cells, thereby
      overcoming one of the major limitations of traditional flow cytometry and
      fluorescence-activated cell sorting. As an example of this approach, we detail a
      binding assay for detecting antibodies secreted from single mouse hybridoma
      cells. Secreted antibodies are detected after only 15 min by co
      compartmentalizing single mouse hybridoma cells, a fluorescent probe and single
      beads coated with anti-mouse IgG antibodies in 50-pl droplets. The beads capture
      the secreted antibodies and, when the captured antibodies bind to the probe, the
      fluorescence becomes localized on the beads, generating a clearly distinguishable
      fluorescence signal that enables droplet sorting at ~200 Hz as well as cell
      enrichment. The microfluidic system described is easily adapted for screening
      other intracellular, cell-surface or secreted proteins and for quantifying
      catalytic or regulatory activities. In order to screen ~1 million cells, the
      microfluidic operations require 2-6 h; the entire process, including preparation
      of microfluidic devices and mammalian cells, requires 5-7 d.

PMID- 23558788
TI  - Polycyclic aromatic hydrocarbons-induced ROS accumulation enhances mutagenic
      potential of T-antigen from human polyomavirus JC.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are the products of incomplete combustion
      of organic materials, which are present in cigarette smoke, deep-fried food, and
      in natural crude oil. Since PAH-metabolites form DNA adducts and cause oxidative
      DNA damage, we asked if these environmental carcinogens could affect transforming
      potential of the human Polyomavirus JC oncoprotein, T-antigen (JCV T-antigen). We
      extracted DMSO soluble PAHs from Deepwater Horizon oil spill in the Gulf of
      Mexico (oil-PAHs), and detected several carcinogenic PAHs. The oil-PAHs were
      tested in exponentially growing cultures of normal mouse fibroblasts (R508), and
      in R508 stably expressing JCV T-antigen (R508/T). The oil-PAHs were cytotoxic
      only at relatively high doses (1:50-1:100 dilution), and at 1:500 dilution the
      growth and cell survival rates were practically unaffected. This non-toxic dose
      triggered however, a significant accumulation of reactive oxygen species (ROS),
      caused oxidative DNA damage and the formation of DNA double strand breaks (DSBs).
      Although oil-PAHs induced similar levels of DNA damage in R508 and R508/T cells,
      only T-antigen expressing cells demonstrated inhibition of high fidelity DNA
      repair by homologous recombination (HRR). In contrast, low-fidelity repair by non
      homologous end joining (NHEJ) was unaffected. This potential mutagenic shift
      between DNA repair mechanisms was accompanied by a significant increase in clonal
      growth of R508/T cells chronically exposed to low doses of the oil-PAHs. Our
      results indicate for the first time carcinogenic synergy in which oil-PAHs
      trigger oxidative DNA damage and JCV T-antigen compromises DNA repair fidelity.

PMID- 23558789
TI  - Pharmacotherapy prevention and management of nutritional deficiencies post Roux
      en-Y gastric bypass.
AB  - Roux-en-Y gastric bypass is the most commonly performed bariatric procedure. It
      is associated with nutritional deficiencies due to gastric reduction, intestinal
      bypass, reduced caloric intake, avoidance of nutrient-rich foods, noncompliance
      with supplementation and poor food tolerability. Although there are multiple
      publications on this topic, there is a lack of consistent guidance for the
      healthcare practitioner caring for the bariatric patient. This article will
      encompass literature reviewing the pharmacotherapy approach to prevention and
      management of nutritional deficiencies since the American Society of Metabolic
      and Bariatric Surgery guidelines were published in 2008.

PMID- 23558790
TI  - Self-locking first stitch in suture reinforcement of the laparoscopic gastric
      sleeve.

PMID- 23558792
TI  - Surgical treatment of sacroiliac joint infection.
AB  - BACKGROUND: Sacroiliac joint infection is rare and frequently missed; purpose of
      this study is to describe the clinical presentations, comorbidities, laboratory
      and imaging findings, surgical options and outcomes of this rare condition.
      MATERIALS AND METHODS: We reviewed all cases of surgical treatment of sacroiliac
      joint infection operated at our institution between January 1994 and December
      2011. Twenty-two patients were included: 14 females and 8 males, with mean age of
      50 years. The mean follow-up period was 34 months. Twenty-four operations were
      performed. Coinciding infection was found in 11 cases (50 %). Twelve patients
      (54.5 %) presented acutely, while ten patients (45.5 %) had chronic infection.
      RESULTS: Tuberculous infection was diagnosed in 5 cases and nonspecific infection
      in 13 cases. In four cases, no organism was isolated. Eleven cases were subjected
      to debridement only, while debridement and arthrodesis was needed in 11 cases.
      Eight patients had excellent clinical results, five good, three fair and four
      poor; one patient was lost to follow-up, and one patient died after 2 weeks. The
      operative technique depended on the course of the infection, bone destruction and
      general condition of the patient. There was a significant change in C-reactive
      protein and erythrocyte sedimentation rate preoperatively and 6 weeks
      postoperatively, while the difference in white blood cell count was
      nonsignificant. CONCLUSIONS: In acute cases, the primary aim should be to save
      joint integrity by early debridement, depending on joint destruction and general
      patient condition. When it is chronic, it is not secure only to debride the
      joint, which should be fused.

PMID- 23558791
TI  - Use of selective serotonin reuptake inhibitors and outcomes in pulmonary arterial
      hypertension.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been suggested
      to offer therapeutic benefit in patients with pulmonary arterial hypertension
      (PAH). We conducted two analyses to explore the association between SSRI use and
      PAH outcomes using the Registry to Evaluate Early and Long-term PAH Disease
      Management (REVEAL Registry). METHODS: First, new users (SSRI-naive patients who
      initiated treatment after enrollment, incident use analysis, n = 220) were
      matched (1:2) with non-SSRI users (nonusers, n = 440) by enrollment center, sex,
      date of most recent visit, age, and 6-min walk distance. Second, a cross
      sectional design was used to compare nonusers (n = 2,463), high-affinity SSRI
      users (n = 430), and non-high-affinity SSRI users (n = 125) at enrollment.
      Mortality and a composite end point defined by events indicative of clinical
      worsening were evaluated. RESULTS: New users had a higher risk of death
      (unadjusted hazard ratio [HR], 1.74; 95% CI, 1.19-2.54; P = .004) and were less
      likely to be free from the composite end point 2 years after enrollment vs
      nonusers (25.7% vs 43.2%, respectively; P < .001). Similarly, among prevalent
      SSRI users (patients with a history of SSRI use at enrollment), high-affinity
      SSRI users were less likely to be free from the composite end point vs nonusers
      (unadjusted HR, 1.20; 95% CI, 1.07-1.36; P = .003). In both analyses, differences
      in outcome were maintained after adjustment for clinical variables previously
      associated with PAH outcomes. CONCLUSIONS: In a large population of patients with
      PAH, incident SSRI use was associated with increased mortality and a greater risk
      of clinical worsening, although we could not adjust for all potential
      confounders.

PMID- 23558793
TI  - The loss of extension test (LOE test): a new clinical sign for the anterior
      cruciate ligament insufficient knee.
AB  - BACKGROUND: This prospective study was created to evaluate the reliability of a
      new clinical test, which we termed the "loss of extension test" (LOE test). The
      LOE test investigates the loss of normal maximum passive extension (MPE) of the
      knee due to an anterior cruciate ligament tear in comparison to the normal MPE of
      the healthy knee. MATERIALS AND METHODS: The study was divided into two
      consecutive parts. Part 1 was designed to assess the side-to-side difference in
      normal MPE in a healthy population. In part 1, 100 healthy adults were enrolled.
      Part 2 was designed to evaluate the LOE test reliability in injured knees. In
      part 2, we included 196 selected patients. RESULTS: In part 1, the average side
      to-side difference in MPE in the healthy population was not statistically
      significant. In part 2, the overall average side-to-side difference in MPE of the
      injured group was 10.1 mm +/- 14.1 (min -20; max 60), which was not statistically
      significant (p = 0.52). An anterior cruciate ligament (ACL) tear was found in 121
      knees among 196 patients. The average side-to-side difference in MPE in the ACL
      insufficient group was 16.9 mm +/- 13.4 (min -20; max 60), which was
      statistically significant (p < 0.0001). The accuracy of the loss of extension
      test was 83.7%, its specificity was 93.3%, its sensitivity was 77.7%, its
      positive predictive value was 95%, and its negative predictive value was 72.2%.
      CONCLUSIONS: The reliability of the LOE test is comparable to those reported in
      the literature for the Lachman test and dynamic tests, so the LOE test could
      represent a useful tool for the diagnosis of the anterior cruciate ligament
      insufficient knee.

PMID- 23558794
TI  - Fractured neck of femur patient care improved by simulated fast-track system.
AB  - BACKGROUND: Fractured neck of femur patients represent a large demand on trauma
      services, and timely management results in improvements in morbidity and
      mortality. NICE guidance, advocating surgery on the day of admission or the
      following day, emphasises this. We set out to investigate whether a simulated
      fast-track management system could improve neck of femur fracture patient care.
      MATERIALS AND METHODS: This prospective study was performed in a district general
      hospital in South West England, following a change in practise. We studied 429
      patients over a 1-year period. Patients were phoned through, by the ambulance
      crew, to a trauma coordinator who arranged prompt radiological assessment and
      review. Patients with confirmed fractures were transferred to an optimisation
      area for orthopaedic and anaesthetic assessment prior to surgery the same day or
      early the following day. Our primary outcome measures were time to theatre (h)
      and length of hospital stay (days/h). RESULTS: Time to theatre reduced from 44.95
      (+/-27.42) to 29.28 (+/-21.23) h. Length of stay reduced from 10 days (245.92 (+/
      131.02) h) to 9 days (225.30 (+/-128.75) h). Both of these improvements were
      statistically significant (P < 0.05). Despite operating on virtually all
      patients, no increase in adverse events was seen, there was no increase in 30-day
      mortality and there were no perioperative deaths. CONCLUSIONS: This coordinated
      management pathway improves the efficiency of the service and reduces inpatient
      length of stay. Increased productivity may lead to financial savings and improve
      our ability to meet guidelines.

PMID- 23558796
TI  - A big step forward in the treatment of refractory systemic lupus erythematosus:
      allogenic mesenchymal stem cell transplantation.

PMID- 23558795
TI  - Retinal blood flow velocity in metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS) is characterized by obesity, insulin
      resistance, dyslipidemia, and hypertension. The Retinal Function Imager (RFI) is
      a new technique for measuring retinal blood-flow velocity. This study aims to
      compare retinal blood flow velocity between MetS and healthy subjects. METHODS:
      Twenty eyes of 20 MetS males and 21 eyes of 21 aged-matched healthy males
      underwent RFI and carotid-femoral pulse wave velocity (PWV) measurement as well
      as assessment of MetS parameters. The results in MetS and healthy subjects were
      compared. RESULTS: The average venular velocity in the MetS patients was
      significantly higher than in the healthy subjects (2.7 +/- 0.0 mm/sec versus 2.5
      +/- 0.0 mm/sec respectively, P=0.013), following adjustment for age, heart rate
      and systolic blood pressure. Carotid-femoral PWV was higher in the MetS
      population than the healthy controls (10.3 +/- 1.2 mm/sec versus 9.3 +/- 1.5
      mm/sec respectively, P=0.005). The diastolic blood pressure and MAP were
      correlated strongly with the arterial blood flow velocities in healthy subjects
      (r=0.503, P=0.020 and r=0.474, P=0.030 respectively) but not in MetS subjects.
      CONCLUSIONS: The RFI was able to distinguish between the retinal blood flow of
      normal and MetS subjects. Higher venular blood flow velocity and the poor
      correlation between velocity and blood pressure of MetS subjects suggest that
      MetS causes microvascular damage.

PMID- 23558799
TI  - Microanatomical study of testis in juvenile ostrich (Struthio camelus).
AB  - The majority of investigations on the testis, as the main organ of male
      reproductive system, have been performed in mammalian species, with few studies
      on bird species. Thus, the structure of the ostrich testis remains largely
      unknown. The aim of this study was to investigate the microanatomical
      characteristics of the testis in five juvenile ostriches. A stereological study
      was performed according to the Delesse principle. The mean volume fraction of the
      seminiferous tubules was 0.569, and the mean volume of the seminiferous tubules
      in an average testis was 1.04 cm(3). The Paraffin-embedded sections were stained
      with hematoxylin and eosin, Masson's trichrome, Alcian blue, and periodic acid
      Schiff stains. Histological studies revealed that the spermatogonial stem cells
      and Sertoli cells were localized inside the seminiferous tubules, close to the
      basement membrane. Inside the tubules a few meiotic cells up to the spermatozoa
      stage were located in a centripetal manner. Outside the tubules, one to three
      layers of euchromatic peritubular myoid cells were present, surrounded by loose
      interstitial connective tissue. A thick tunica albuginea contained many myoid
      cells and some rete ducts, with the latter extending from the hilus to the free
      surface of the testis. Straight seminiferous tubules were distributed in the
      lateral surfaces and hilar portions of the capsule but were rare in the free
      surface. These capsular rete ducts may participate in testicular fluid transit
      from the distal tubules through the capsule.

PMID- 23558800
TI  - Variation in the hypothenar muscles and its impact on ulnar tunnel syndrome.
AB  - Compression of the ulnar nerve at Guyon's canal can be caused not only by tumor
      like structures, a fibrotic arch, a ganglion, lipoma, aneurysm or thrombosis but
      also by anomalous hypothenar muscles which are reviewed here. For the search of
      relevant papers, PubMed and crucial anatomical textbooks were consulted. The
      abductor digiti minimi is the most variable hypothenar muscle. It can possess one
      to three muscle bellies. Additional heads can arise from the flexor retinaculum,
      the palmaris longus tendon, the pronator quadratus tendon or the deep fascia of
      the palmar side of the forearm. Our own case of an aberrant abductor digiti
      minimi appearing like connective tissue and originating in the antebrachial
      fascia is included here. Hematoxylin and eosin staining revealed that
      macroscopically non-muscle-like tissue contained skeletal muscle tissue. The
      muscle itself resembled other described cases. In addition, at the flexor digiti
      minimi accessory heads with origin from the flexor retinaculum, the antebrachial
      fascia or the long flexor muscles of the forearm can be detected. By contrast,
      the opponens digiti minimi mostly lacks variations and is sometimes missing. In
      our opinion, this is due to its hidden location. However, in few cases an
      additional head can arise from the lower arm aponeurosis. Furthermore, additional
      (fourth) hypothenar muscles might be expressed. These muscles are characterized
      by origins in the forearm and insertions on the head of the 5th metacarpal bone
      or on the 5th proximal phalanx. It must be noted that accessory hypothenar
      muscles might look like connective tissue at first glance. Often their origin
      extends to the antebrachial fascia. This can be explained by the phylogenetic
      fact that all intrinsic muscles of the hand are derived from muscle masses that
      originated in the forearm. In the opinion of several authors, ulnar nerve
      compression mostly is evoked by hyper trophied variant hypothenar muscles due to
      overuse as for example in carpenters. In some rare cases, an aberrant hypothenar
      muscle can also evoke median nerve compression. 

PMID- 23558801
TI  - C7 nerve root sensory distribution in peripheral nerves: a bold functional
      magnetic resonance imaging investigation at 9.4 T.
AB  - INTRODUCTION: In this study we used a rat model to elucidate the linear make-up
      of each major nerve of the upper limb by the C7 root through sensory stimulation
      and functional magnetic resonance imaging (fMRI). METHODS: The C7 nerve root and
      major nerves of the right forelimb were stimulated electrically. Blood oxygen
      level-dependent functional magnetic resonance imaging (BOLD fMRI) was performed
      concurrently. Voxel overlap within the primary sensory cortex was calculated.
      RESULTS: C7 comprised sensation in <1% in the musculocutaneous nerve, 6% in the
      ulnar nerve, 16% in the radial nerve, and 19% in the median nerve (P<0.005 for
      each). The overlap was always <25% for each major nerve. CONCLUSIONS: This study
      helps explain why C7 is a suitable donor for brachial plexus injury treatment and
      why there is only a transient sensory deficit after transfer.

PMID- 23558802
TI  - Prevalence of porcine hokovirus and its co-infection with porcine circovirus 2 in
      China.
AB  - Here, we report the frequency of porcine hokovirus (PHoV) infection and its co
      infection with porcine circovirus 2 (PCV2) in China. A total of 485 domestic pig
      samples were tested for both PHoV and PCV2, and NS1 gene sequences from 11 PHoV
      strains were used for phylogenetic analysis. The prevalence of PHoV and PCV2 was
      51.3 % and 36.3 %, respectively, and co-infection occurred in 20.2 %. PHoVs from
      the Chinese mainland showed a close relationship to those isolated in Hong Kong.
      Co-infection with both viruses was prevalent, and PHoV may contribute to the
      induction of postweaning multisystemic wasting syndrome (PMWS). 

PMID- 23558803
TI  - Cardiology Journal: from Chopin's revolutionary etude toward the Argentinean
      tango.

PMID- 23558804
TI  - Hypertension in aortic stenosis: more questions than answers.
AB  - Although hypertension and aortic stenosis are the most common cardiovascular
      diseases, the impact of hypertension on the natural history of aortic stenosis,
      the structure and function of the left ventricle, the assessment of valve defect
      severity and its progression are not fully understood. Hypertension not only can
      modify the exploratory findings of aortic stenosis, but may also interfere with
      the assessment of severity, and even have an impact on patients outcome. In the
      absence of specific cohort studies, the nature of the association between aortic
      stenosis and high blood pressure is not clear and the published results are often
      contradictory. Unknown is the true frequency of both conditions, the rules of
      diagnosis and the treatment itself.

PMID- 23558805
TI  - Controversies in the management of the renal artery stenosis.
AB  - Optimal management of renal artery stenosis has continued to remain elusive. The
      previous non randomized studies and registry data suggested a benefit of renal
      artery stenting. However, the recently completed randomized studies comparing
      renal stenting to medical management failed to show any benefit. These studies
      had some flaws in their design and methodology. In an appropriately selected
      patient population renal artery stenting may have a role. In addition, there
      might be some role of adjunctive therapies like antiplatelet medications and
      embolic protection. This review summarizes the current literature on this
      controversial topic.

PMID- 23558806
TI  - Influence of aerobic training on neurohormonal and hemodynamic responses to head
      up tilt test and on autonomic nervous activity at rest and after exercise in
      patients after bypass surgery.
AB  - BACKGROUND: Little is known about the influence of aerobic training on the
      neurohormonal and hemodynamic responses to head-up tilt (HUT) and on autonomic
      balance at rest and after exercise in optimally treated, low risk post-coronary
      artery bypass grafting (CABG) patients. METHODS: One hundred male patients, mean
      age 56 +/- 6 years, 3 months after CABG, were randomized to either 6-week
      training on cycloergometer, 3 times a week, at 70-80% of max tolerated heart rate
      (HR) (training group, n = 50) or to a control group (n = 50). At baseline and at
      the end of the study, all patients underwent: (1) cardiopulmonary exercise test
      with HR recovery (HRR) assessment; (2) 60% HUT during which HR, blood pressure
      (BP), stroke volume (SV by impedance cardiography) were monitored and blood
      samples were taken for determination of plasma catecholamines and ANP levels, and
      plasma renin activity; (3) assessment of HR variability (HRV) in the time and
      frequency domains at rest. RESULTS: During the final tests, HUT-induced changes
      in HR, BP, SV, cardiac output, total peripheral resistance, and noradrenaline
      were significantly lower in training group than in controls. In addition, after
      training faster post-exercise HRR, increased SDNN and a tendency towards an
      increase in the high frequency HRV power spectrum were found. CONCLUSIONS:
      Aerobic training improved neurohormonal and hemodynamic responses to head-up tilt
      test and favorably modified sympatho-vagal balance in low risk post-CABG
      patients.

PMID- 23558807
TI  - Outcomes and effectiveness of bilateral percutaneous transluminal renal artery
      stenting in patients with critical bilateral renal artery stenosis.
AB  - BACKGROUND: The aim of this study was to assess the effects of percutaneous
      bilateral renal artery stenting in patients with atherosclerotic renal artery
      stenosis and in-hospital and 4 month outcome of the procedure, focusing on the
      changes in renal function and blood pressure. METHODS: Five consecutive patients
      (mean age: 64.8 +/- 9.7 years, 1 women) with bilateral renal artery stenoses
      underwent percutaneous interventions. We compared blood pressure, number of oral
      antihypertensive medications, and renal function changes preprocedure and
      postprocedure at 4 months follow-up. RESULTS: A total of 5 bilateral
      atherosclerotic renal artery stenosis patients underwent percutaneous
      transluminal renal angioplasty and 10 stents were placed. Although systolic and
      diastolic blood pressures were significantly decreased in follow-up period,
      glomerular filtration rates were not significantly changed as compared with
      baseline data (p = 0.009, p = 0.008, p = 1.00, respectively). Also, the number of
      oral antihypertensive medications were significantly decreased at follow-up
      period (p = 0.03). CONCLUSIONS: Bilateral renal artery stenting provides a
      beneficial outcome such as stabilization of renal functions, significant
      improvement in blood pressure control and reduction in the number of oral
      antihypertensive medications at follow-up.

PMID- 23558808
TI  - Exendin-4 attenuates ischemia-induced ventricular arrhythmias in rats.
AB  - BACKGROUND: Glucagon-like peptide-1 and its receptor agonist-exendin-4 (Ex-4)
      have been shown to provide beneficial effects for cardiovascular diseases. This
      study investigated the effects of Ex-4 on ischemia-induced ventricular
      arrhythmias in rats. METHODS: Anesthetized male rats were once treated with Ex-4
      (5 MUg/kg, i.v.) 1 h before ischemia in the absence and/or presence of 5
      hydroxydecanoic acid (5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial
      ATP-sensitive potassium [KATP] channels) which were once injected 10 min before
      ischemia. And then subjected to ischemia for 30 min. Ventricular arrhythmias were
      assessed. RESULTS: During the 30-min ischemia, Ex-4 significantly reduced the
      incidence of ventricular fibrillation (VF) (p < 0.05). The duration of
      ventricular tachycardia (VT) + VF, the number of VT + VF episodes and the
      severity of arrhythmias were all significantly reduced by Ex-4 compared to those
      in myocardial ischemia group (p < 0.05 for all). Administration of 5-HD abolished
      the protective effects of Ex-4 on VF incidence, the duration of VT + VF, the
      number of VT + VF episodes and the severity of arrhythmias (p < 0.05 for all).
      CONCLUSIONS: This study suggested that Ex-4 could attenuate ischemia-induced
      ventricular arrhythmias in rats in which mitochondrial KATP channels may be
      involved.

PMID- 23558809
TI  - Outcomes of invasive treatment in very elderly Polish patients with non-ST
      segment-elevation myocardial infarction from 2003-2009 (from the PL-ACS
      registry).
AB  - BACKGROUND: Elderly patients with non-ST-segment elevation myocardial infarction
      (NSTEMI) are rarely included in randomized trials due to concomitant diseases. As
      a result, invasive treatment and aggressive pharmacotherapy are used less
      frequently in this group. The aim of the study was to analyze the impact of
      invasive treatment used for elderly patients (>= 80 years) with NSTEMI from 2003
      2009 and its impact on 24-month outcomes. METHODS: We performed analysis of
      13,707 elderly patients, out of 78,422 total NSTEMI patients, enrolled in the
      prospective, nationwide, Polish Registry of Acute Coronary Syndromes (PL-ACS)
      from 2003 to 2009. RESULTS: The percentage of elderly NSTEMI population was
      17.5%. Invasive treatment received 24% of them. In-hospital complications
      (stroke, reinfarction and death) were significantly less frequent in the invasive
      group, with the exception of major bleeding, which occurred almost three times
      more frequently (2.9% vs. 1.1%, p < 0.0001) in the invasive group. The 24-month
      mortality was lower (29.4% vs. 50.4%, p < 0.0001) in the invasive group and
      remained so after matching patients by the propensity score method (31.1% vs.
      40.9%, p < 0.0001). From 2003 to 2009 the use of thienopyridines, beta-blockers
      and statins rose significantly. The frequency of invasive strategy increased
      significantly, from 10% in to over 50% in 2009. The frequency of major bleeding
      increased twofold, however a significant reduction in the 24-month mortality was
      observed over the years. CONCLUSIONS: Elderly patients with NSTEMI benefit
      significantly from invasive strategies and modern pharmacotherapy recommended by
      treatment guidelines. Nevertheless, this approach is associated with an increased
      incidence of major bleeding.

PMID- 23558810
TI  - Percutaneous mitral balloon valvuloplasty beyond 65 years of age.
AB  - BACKGROUND: The profile of subjects undergoing percutaneous mitral balloon
      valvuloplasty (PMBV) in developed countries has shifted toward the elderly. In
      the group of elderly patients long-term results after PMBV, as well prognostic
      factors that may improve patient selection for this procedure have not been fully
      elucidated. Aim of the study was to evaluate the safety and efficacy of PMBV for
      the treatment of mitral stenosis in patients older than 65. METHODS: The studied
      group consists of 132 consecutive patients aged > 65, who underwent PMBV. All
      PMBV procedures were performed by the antegrade transvenous approach using the
      Inoue balloon system. RESULTS: Procedural success, defined as mitral valve area
      >= 1.5 cm2 and mitral regurgitation L 2+, was obtained in 105 (79.5%) patients.
      Mean follow-up was 6.25 +/- 4.33 years. Echo score > 8 and higher mean mitral
      valve gradient were significant independent predictors of inadequate immediate
      result. Survival curves showed that for the whole studied group after PMBV the 3
      , 5-, and 10-year overall survival rates were significantly better in patients
      with left atrium diameter L 5.0 cm before intervention (95.4%, 91.3% and 80.5%
      vs. 89.6%, 69.5%, and 53.7%, respectively; p = 0.002). Survival free of mitral
      valve intervention or heart failure >= NYHA III was significantly better for
      patients with good immediate result and mean pulmonary artery pressure after PMBV
      < 25 mm Hg. CONCLUSIONS: PMBV is safe and efficacious in elderly patients with
      symptomatic mitral stenosis. Long-term results are good and related mainly to the
      quality of the procedure.

PMID- 23558811
TI  - Statin pretreatment and presentation patterns in patients with coronary artery
      disease.
AB  - BACKGROUND: Knowledge on the impact of pretreatment statin therapy on
      presentation of patients with coronary artery disease (CAD) is incomplete. The
      aim of this study was to investigate the impact of statin pretreatment on
      presentation patterns of patients with CAD. METHODS: The study included 12,989
      consecutive patients with CAD who underwent coronary angiography. The primary
      outcome was presentation as stable angina or acute coronary syndrome (ACS)
      according to statin pretreatment. RESULTS: At the time of presentation, 8147
      (62.7%) patients were receiving statins and 4842 (37.3%) patients were not
      receiving statins. Presentation pattern in patients receiving statins vs. those
      not receiving statins was: stable angina in 5939 (72.9%) vs. 2102 (43.4%)
      patients; odds ratio (OR) = 3.50, 95% confidence interval (CI) 3.25-3.78; p <
      0.001; unstable angina in 1435 (17.6%) vs. 1011 (20.9%) patients; OR = 0.81, 95%
      CI 0.74-0.89; p < 0.001; non- -ST-segment elevation myocardial infarction
      (NSTEMI) in 463 (5.7%) vs. 505 (10.4%) patients; OR = 0.52, 95% CI 0.45-0.59; p <
      0.001; and ST-segment elevation myocardial infarction (STEMI) in 310 (3.8%) vs.
      1224 (25.3%) patients; OR = 0.11, 95% CI 0.10-0.13; p < 0.001. Gensini score
      (median [25th to 75th percentiles]) was significantly higher in patients on
      statins presenting with stable angina (26.5 [13.0-59.5] vs. 21.0 [10.5-47.4]; p <
      0.001) or ACS (39.3 [17.5-77.0] vs. 37.0 [18.0-64.0]; p = 0.001). In
      multivariable analysis, statin therapy was an independent correlate of reduced
      presentation with ACS (adjusted OR = 0.35 [0.32-0.39]; p < 0.001) or STEMI
      (adjusted OR = 0.18 [0.16-0.22]; p < 0.001). CONCLUSIONS: Despite having a higher
      coronary atherosclerotic burden, patients with CAD on statin therapy have reduced
      odds for presentation with ACS and STEMI compared to patients not receiving
      statins.

PMID- 23558812
TI  - Impaired atrial electromechanical function and atrial fibrillation promotion in
      alloxan-induced diabetic rabbits.
AB  - BACKGROUND: Diabetes mellitus (DM) is an independent risk factor for atrial
      fibrillation (AF). However, the underlying mechanisms are still not clearly
      elucidated. The aim of this study was to evaluate the atrial electromechanical
      function, atrial electrophysiological changes and AF inducibility in alloxan
      induced diabetic rabbits. METHODS: In 8 alloxan-induced diabetic rabbits and 8
      controls, we evaluated atrial electromechanical function by tissue Doppler
      imaging. Isolated Langendorff-perfused rabbit hearts were prepared to measure
      atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial
      conduction time (IACT) and vulnerability to AF. Atrial interstitial fibrosis was
      evaluated by Sirius-Red staining. RESULTS: Compared with controls, left atrial
      lateral wall Pa'-start interval (Pastart) and right atrial wall Pastart were
      increased in diabetic rabbits. AERPD was increased and IACT was prolonged in
      diabetic rabbits. Inducibility of AF in diabetic group was significant higher
      than controls (6/8 vs. 1/8, p < 0.05). Extensive interstitial fibrosis was
      observed in the DM group (p < 0.01). Correlation analysis showed that right
      atrial wall Pastart, Pa'-peak interval (Papeak) and total electromechanical
      activity (TEMA); left atrial lateral wall Papeak and TEMA, left atrial posterior
      wall TEMA, and IACT were correlated with atrial areas of fibrosis. CONCLUSIONS:
      Atrial electromechanical function is impaired in diabetic rabbits, and is
      associated with atrial fibrosis and interatrial electrical conduction delay.

PMID- 23558813
TI  - A comparison of cardiac magnetic resonance imaging peri-infarct border zone
      quantification strategies for the prediction of ventricular tachyarrhythmia
      inducibility.
AB  - BACKGROUND: Peri-infarct border zone (BZ) as quantified by late gadolinium
      enhancement (LGE) on cardiac magnetic resonance imaging (MRI) has been proposed
      as a risk stratification tool, and is associated with increased mortality. BZ has
      been measured by various methods in the literature. We assessed which BZ analysis
      best predicts inducible arrhythmia during electrophysiological study (EPS).
      METHODS: LGE was performed in 47 patients with coronary artery disease referred
      for EPS to assess for ventricular tachycardia (VT). LGE data was analyzed for BZ
      quantification by 3 previously published methods. Method I (BZ-I) used pixels 2-3
      standard deviations over the mean of normal tissue, expressed as % of left
      ventricular mass, Method II (BZ-II, as described by Yan) and Method III (BZ-III,
      as described by Schmidt). EPS results were classified as negative (non-inducible)
      or positive (monomorphic VT - MVT). RESULTS: There were 47 subjects-age 61.7
      years, 72% male. During EPS, 20 patients were non-inducible and 18 had induced
      MVT. Ejection fraction was not significantly different between non-inducible
      patients and those with MVT (34.1% vs. 28.5%, p = 0.13). BZ-I was significantly
      different (1.4% vs. 2.6%, p = 0.001), but not BZ-II (7.9% vs. 6.9%, p = 0.68) or
      BZ-III (2.7 g vs. 2.1 g, p = 0.88). Multivariate analysis demonstrated that only
      BZ-I was an independent predictor of EPS outcome after controling for infarct
      size (OR 1.97 per % change, 95% CI 1.04-3.73, p = 0.04). CONCLUSIONS: This study
      demonstrates significant variability between the published methods for measuring
      BZ. Also, BZ-I is a stronger predictor of inducible MVT during EPS than ejection
      fraction and infarct size. BZ may be another LGE marker of elevated risk of
      arrhythmia.

PMID- 23558814
TI  - Congenital long QT syndrome of particularly malignant course connected with so
      far unknown mutation in the sodium channel SCN5A gene.
AB  - This article presents the case of a 35 year-old male with long QT syndrome (LQTS)
      who suffered from sudden cardiac arrest. Even though asymptomatic LQTS had been
      diagnosed, the patient had not undergone any medical treatment. His two
      daughters, aged four and seven, were also diagnosed with LQTS. A new, previously
      unknown, mutation of the SCN5A gene has been found in the family. The older
      daughter died suddenly before implantable cardioverterdefibrillator (ICD)
      implantation, but the father and the younger daughter have been implanted with
      ICDs.

PMID- 23558815
TI  - Long-term survivor diagnosed with arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.
AB  - The subject was a 70 year-old man who survived for 31 years after being diagnosed
      with right ventricular cardiomyopathy, having undergone right ventricular (RV)
      aneurysmectomy at the age of 39. His arrhythmia and syncopal attacks were
      effectively abolished after the original aneurysmectomy. Although he frequently
      suffered from right heart failure, hemodialysis improved his status. However, the
      patient died due to worsening anasarca caused by RV low output syndrome. Autopsy
      results indicated extensive replacement of the RV myocardium with fibrous and
      fatty tissues. This case suggests that patients with arrhythmogenic RV
      cardiomyopathy, but without left ventricular abnormalities and rapid ventricular
      arrhythmia, have a relatively favorable prognosis, although RV abnormalities may
      be progressive.

PMID- 23558816
TI  - Can multi-slice computed tomography of the heart be useful in patients with
      epicardial leads?
AB  - New visualization methods are helpful in the noninvasive diagnosis of heart
      diseases. However, sometimes epicardial and endocardial leads can cause problems
      due to a large number of artifacts. Based on the presented case, we conclude that
      it is possible to perform multi-slice computed tomography of coronary arteries
      despite the coexistence of transvenous and epicardial leads.

PMID- 23558817
TI  - Unstable angina in a young woman with Hodgkin's lymphoma.
AB  - We present the case of a 30 year-old woman - 16 months after successful treatment
      of Hodgkin's lymphoma (chest location) with chemotherapy (including doxorubicin)
      and radiotherapy - with recurrent chest pain and dyspnea. In ambulatory event
      telemetry, she reported nocturnal chest pain with transient ST elevation
      characteristic for acute cardiac ischemia. Urgent coronary angiography with
      intravascular ultrasound and virtual histology visualization revealed 70%
      fibrotic stenosis in the proximal segment of the left anterior descending artery
      successfully treated with a drug-eluting stent implantation. This case is
      especially noteworthy because of the short period from initial therapy to the
      symptomatic coronary artery disease that is entirely unlike the reported mean
      latency period of several years.

PMID- 23558818
TI  - Difficult dual-stage transcutaneous multiple lead extraction with loss of
      external silicone tube of broken lead.
AB  - The extraction of three implanted (18-, 16-, and ten year-old) damaged
      nonfunctional leads was complicated by a lead breaking and losing its external
      silicone tube. The missing part of the lead was invisible on X-ray, but was
      visible in ECHO as a thin, corded, very mobile limp structure without metallic
      reflection. Incomplete lead extraction did not cease laboratory symptoms of
      infection. The lost silicone tube was grasped and removed via femoral approach
      during the subsequent transesophageal echocardiography (TEE)-guided procedure.
      The presented case indicates that the criterion of full radiological success is
      not always correct, exposes the utility of ECHO techniques for X-ray-invisible
      broken lead fragments, and indicates the possibility of success for such TEE
      guided procedures.

PMID- 23558819
TI  - Acute left main coronary artery occlusion following inadvertent delivery of
      radiofrequency energy during ventricular tachycardia ablation successfully
      treated by rescue angioplasty with stenting: a two-year follow-up.
AB  - Radiofrequency catheter ablation (RFCA) is a treatment mode in patients with
      recurrent, symptomatic, ventricular arrhythmias. A rare but potentially life
      threatening complication of RFCA includes injury to the coronary arteries, which
      leads to acute occlusion and myocardial infarction. In the few reported cases,
      the most frequently affected vessel has been the left main coronary artery. We
      present the case of a 28 year-old female. During the RFCA procedure, an acute
      occlusion of the left main coronary artery occurred, which was treated
      successfully with emergency angioplasty.

PMID- 23558820
TI  - Eisenmenger's syndrome and agenesis of the right pulmonary artery: a case of
      double diagnosis.
AB  - We present a case of patent ductus arteriosus with severe pulmonary hypertension
      with the rare association of absent right pulmonary artery.

PMID- 23558821
TI  - Diagnostic challenge of artifactual electrocardiographic tachyarrhythmias.
AB  - Electrocardiographic artifacts may generate recordings mimicking supraventricular
      and ventricular tachyarrhythmias. This report describes the diagnostic challenge
      presented by Holter or loop recordings in two patients, one with pseudo-atrial
      flutter and the other with pseudo- -polymorphic ventricular tachycardia.

PMID- 23558822
TI  - Statement on matching language to the type of evidence used in describing
      outcomes data.

PMID- 23558823
TI  - Introduction for 20 years of research on ordered mesoporous materials.

PMID- 23558824
TI  - Antibodies to deamidated gliadin peptides: an accurate predictor of coeliac
      disease in infancy.
AB  - Immunoglobulin G antibodies against deamidated gliadin peptides are now known to
      have diagnostic accuracy comparable to tissue transglutaminase and endomysium
      autoantibodies in patients with coeliac disease. However, little is known about
      their predictive value in infants with a suspected gluten enteropathy. We tested
      whether deamidated gliadin immunoglobulin G antibodies are more reliable than
      traditional tests for coeliac disease screening in infancy. Sixty-five children
      under 2 years of age (42 with malabsorption, 23 controls) were tested for
      deamidated gliadin immunoglobulin G, tissue transglutaminase and endomysium
      immunoglobulin A, and gliadin immunoglobulins A and G . Thirty-seven of the 42
      children with malabsorption had deamidated gliadin antibodies, associated with
      tissue transglutaminase and endomysial antibodies in 33, and with gliadin
      immunoglobulins A and G in 21 and 29, respectively. Intestinal biopsy was
      performed in 34 of the 37 children positive for deamidated gliadin antibodies.
      Thirty-two/34 showed villous atrophy consistent with coeliac disease, while the
      remaining two had a Marsh 1 and a normal mucosa, respectively. Only gliadin
      immunoglobulins A (4.3%) and G (39.1%) were found in controls. The sensitivity of
      deamidated gliadin, tissue transglutaminase and endomysial antibodies for coeliac
      disease was significantly higher than that of gliadin immunoglobulins G and A.
      High titre deamidated gliadin antibodies correlated with severe intestinal
      damage. Deamidated gliadin antibodies showed a higher diagnostic accuracy for
      coeliac disease than gliadin antibodies in infancy. High titre deamidated gliadin
      antibodies predict a severe gluten-dependent duodenal damage.

PMID- 23558825
TI  - TNF-alpha-secreting B cells contribute to myocardial fibrosis in dilated
      cardiomyopathy.
AB  - PURPOSE: Excessive inflammation responses mediated by CD4(+) T cells contributes
      to myocardial fibrosis in dilated cardiomyopathy (DCM) resulting from viral
      myocarditis. Recently, some scholars discovered that B cells harbored an abnormal
      pro-inflammatory capacity besides the production of autoantibodies. Thus, we
      aimed to explore whether and which type of B cells act on myocardial fibrosis in
      DCM. METHODS: A total of 56 newly hospitalized DCM patients were studied, and
      among these, 17 patients accepted the gadolinium enhanced cardiovascular magnetic
      resonance imaging (MRI) for myocardial fibrosis evaluations. RESULTS: B cell
      functions including the frequency and proliferation were significantly elevated
      in DCM patients. After screening the important cytokines including IL-1beta, IL
      6, IL-10, IL-17, TNF-alpha and TGF-beta produced in these B cells by flow
      cytometry, we found that only the TNF-alpha-secreting B cells were obviously
      increased. Furthermore, the TNF-alpha protein secretion and mRNA levels were also
      enhanced in LPS-stimulated B cell isolated from DCM patients. In addition, 10
      patients (59%) with increased TNF-alpha-secreting B cells showed late enhancement
      and boosted serum procollagen type III compared with the other 7 patients (41%)
      whose enhancement could not be detected. Moreover, the frequencies of TNF-alpha
      secreting B cells were negatively correlated with LVEF and positively correlated
      with LVEDD, NT-proBNP and procollagen type III in all of the DCM patients.
      CONCLUSIONS: Our study firstly suggested that TNF-alpha-secreting B cells were
      involved in myocardial fibrosis, which revealed the new pathogenic mechanism of B
      cells in DCM, and therapeutic targets against these cells might be valuable.

PMID- 23558826
TI  - The role of young users in determining long-term care expenditure in Norway.
AB  - AIMS: In Norway, it is the responsibility of the country's 429 municipalities to
      provide long term care (LTC) services to their residents. Recent years have seen
      a sharp rise in the number of LTC users under the age of 65. This article aims to
      explore the effect of this rise on LTC expenditure. METHODS: Panel data models
      are used on data from municipalities from 1986 to 2011. An instrumental variable
      approach is also utilized to account for possible endogeneity related to the
      number of young users. RESULTS: The number of young users appears to have a
      strong effect on LTC expenditure. There is also evidence of municipalities
      exercising discretion in defining eligibility criteria for young users in order
      to limit expenditure. CONCLUSIONS: The rise in the number of young LTC users
      presents a long-term challenge to the sustainability of LTC financing. The
      current budgeting system appears to compensate municipalities for expenditure on
      young LTC users.

PMID- 23558827
TI  - Report of the American College of Cardiology (ACC) Scientific Sessions 2013, San
      Francisco--highlighting late-breaking trials.
AB  - The American College of Cardiology's (ACC) 62nd Annual Scientific Session was
      held at the Moscone Center, San Francisco, from March 9-11, 2013. The meeting
      focused on the "transformation of cardiovascular care, from discovery to
      delivery", featured over 20 late-breaking clinical trials and 2,000 abstracts.
      These sessions gave notable exposure and recognition of studies likely to
      significantly affect clinical practice. There were 21 trials scheduled for
      presentation in 5 featured Late-Breaking Clinical Trial sessions, but one, the
      PREVAIL trial, was not presented because of a failure to observe an embargo. I
      summarize and overview both the late-breaking trials presented at ACC 2013 and
      the PREVAIL trial.  

PMID- 23558828
TI  - Effect of exercise on circulating endothelial progenitor cells in microvascular
      angina.
AB  - BACKGROUND: Circulating endothelial progenitor cells (EPCs) might limit
      endothelial dysfunction in patients with microvascular angina (MVA). Endothelial
      colony-forming cells (ECFCs; displaying the CD34+/KDR+/CD45- phenotype) are
      currently regarded as true EPCs. The aim of this study was to evaluate exercise
      induced ECFC mobilization and platelet reactivity in patients with MVA or with
      obstructive coronary artery disease (CAD). METHODS AND RESULTS: Exercise stress
      test (EST) was performed in 20 MVA patients, 20 CAD patients and 20 controls.
      Platelet reactivity was assessed before and after EST as formation of monocyte
      platelet aggregates (MPAs) and CD41 platelet expression, without and with
      adenosine diphosphate (ADP) stimulation. ECFC number was measured before and 24h
      after EST. At rest, MPAs and CD41 platelet expression increased more with ADP in
      MVA patients (+71+/-11.0% and +37+/-7.5%, respectively), than in CAD patients
      (+37+/-8.6% and +19+/-4.5%, respectively) and controls (+29+/-3.5% and +21+/
      3.1%, respectively; P<0.001 for both). At rest, ECFCs tended to be lower in CAD
      patients, compared to MVA patients and controls (4.1+/-5.0%, 7.2+/-6.0% and 7.3+/
      7.0% cells/10(5), respectively; P=0.056). After EST, ECFCs increased less in MVA
      patients (+2.8+/-11) compared to CAD patients (+3.3+/-15; P<0.05) and controls
      (+7.4+/-24; P<0.01). CONCLUSIONS: In MVA patients, EST is able to blunt the
      peculiar increase of platelet reactivity to ADP present at rest; in contrast, no
      potential protective response of ECFCs to exercise was seen in these patients.

PMID- 23558829
TI  - Corpus callosum integrity and neuropsychological performance after traumatic
      brain injury: a diffusion tensor imaging study.
AB  - OBJECTIVES: (1) Detailed analysis of diffusion tensor imaging (DTI) parameters
      (fractional anisotropy and radial diffusivity) to evaluate white matter integrity
      in the corpus callosum (CC), and (2) examine correlations between DTI data and
      performance on multiple measures of cognitive functioning. PARTICIPANTS: Twelve
      individuals with a history of complicated mild, moderate, or severe traumatic
      brain injury (TBI) who were an average of 1.7 years postinjury and 12 control
      participants. MAIN MEASURES: Standardized and experimental neuropsychological
      tests; detailed analysis of DTI parameters. RESULTS: The TBI group demonstrated
      DTI values suggesting decreased white matter integrity and correlations with
      severity of injury. Both groups showed correlations between DTI parameters and
      cognitive measures, with more significant correlations observed for the TBI
      group. White matter changes in the CC were evident chronically and were related
      to severity of injury. CONCLUSIONS: Diffusion tensor imaging parameters
      suggesting disruptions in white matter in the CC may be implicated in impaired
      performance, both in terms of cognitive tasks and reaction time, after TBI.

PMID- 23558830
TI  - Perioperative smoking behavior of Chinese surgical patients.
AB  - BACKGROUND: Surveys suggest that, consistent with a high smoking prevalence,
      Chinese smokers in the general population report little interest in quitting. In
      other cultures, surgery is a powerful teachable moment for smoking cessation,
      increasing the rate of spontaneous quitting. We determined the perioperative
      tobacco use behavior of Chinese patients scheduled for elective surgery who smoke
      cigarettes and factors associated with both preoperative intent to abstain and
      self-reported smoking behavior at 30 days postoperatively. Specifically, we
      tested the hypothesis that perception of the health risks of smoking would be
      independently associated with both preoperative intent to abstain and self
      reported abstinence at 30 days postoperatively. METHODS: Patients >=18 years of
      age scheduled for elective noncardiovascular surgery at Peking Union Medical
      College Hospital in Beijing, China, were assessed preoperatively and up to 30
      days postoperatively for factors associated with smoking behavior, including
      indices measuring knowledge of smoking-related health risks. RESULTS: Of the 227
      patients surveyed at baseline, most (164, 72%) intended to remain abstinent after
      hospital discharge. For the 204 patients contacted at 30 days postoperatively,
      126 (62%) self-reported abstinence. In multivariate analysis, factors associated
      with preoperative intent to abstain after surgery included older age, self
      efficacy for abstaining, and undergoing major surgery; factors associated with
      abstinence included older age, self-efficacy, major surgery, and preoperative
      intent to abstain. Higher perception of benefits from quitting was associated
      with intent, but not abstinence. Knowledge of the health risks caused by smoking
      was not found to be associated with either intent or abstinence, so that the
      hypothesis was not supported. CONCLUSIONS: Both intent to quit and self-efficacy
      for maintaining abstinence appear to be much higher in Chinese surgical patients
      than in prior surveys of the general Chinese population, and the majority of
      surgical patients maintained abstinence for at least 30 days. These findings
      suggest that surgery can serve as a powerful teachable moment for smoking
      cessation in China.

PMID- 23558831
TI  - Fetal assessment for anesthesiologists: are you evaluating the other patient?
AB  - Suboptimal communication between anesthesiologists and obstetricians can be
      associated with unintended poor maternal and neonatal outcomes, especially for
      emergency cesarean deliveries. Obstetricians use the results of antepartum and
      intrapartum fetal assessments to assess fetal well-being and to make decisions
      about the timing and method of delivery. Because abnormal results may lead to the
      need for urgent or emergency cesarean deliveries, these decisions may directly
      impact anesthetic care. Lack of familiarity with fetal assessments and the
      significance of the results may thus hinder the communication necessary for
      optimal patient care. In this review article, we discuss the current antepartum
      and intrapartum fetal assessment modalities, including the nonstress test,
      biophysical profile, Doppler velocimetry, electronic fetal heart rate monitoring,
      fetal electrocardiogram (STAN-ST waveform analysis), and fetal pulse oximetry.
      The physiologic basis behind these modalities and the available evidence
      regarding their utility in clinical practice are also reviewed. The 2008 National
      Institute of Child Health and Human Development workshop report on electronic
      fetal monitoring categories, which are incorporated into the American College of
      Obstetricians and Gynecologists guidelines for intrapartum care, is examined. The
      implications of test interpretation to the practice of obstetric anesthesiology
      is also discussed. Anesthesia provider understanding of fetal assessment
      modalities is essential in improving communication with obstetricians and
      improving the planning of cesarean deliveries for high-risk obstetric patients.

PMID- 23558832
TI  - Increased red blood cell transfusions are associated with worsening outcomes in
      pediatric heart transplant patients.
AB  - BACKGROUND: Red blood cell (RBC) transfusions are associated with increased
      morbidity. Children receiving heart transplants constitute a unique group of
      patients due to their risk factors. Although previous studies in nontransplant
      patients have focused primarily on the effects of postoperative blood
      transfusions, a significant exposure to blood occurs during the intraoperative
      period, and a larger percentage of heart transplant patients require
      intraoperative blood transfusions when compared with general cardiac surgery
      patients. We investigated the relationship between clinical outcomes and the
      amount of blood transfused both during and after heart transplantation. We
      hypothesized that larger amounts of RBC transfusions are associated with
      worsening clinical outcomes in pediatric heart transplant patients. METHODS: A
      database comprising 108 pediatric patients undergoing heart transplantation from
      2004 to 2010 was queried. Preoperative and postoperative clinical risk factors,
      including the amount of blood transfused intraoperatively and 48 hours
      postoperatively, were analyzed. The outcome measures were length of hospital
      stay, duration of tracheal intubation, inotrope score, and major adverse events.
      Bivariate and multivariate analyses were performed to control for simultaneous
      risk factors and determine outcomes in which the amount of blood transfused was
      an independent risk factor. RESULTS: Ninety-four patients with complete datasets
      were included in the final analysis. Eighty-eight percent received RBC
      transfusions, with a median transfusion amount of 38.7 mL/kg. A multivariate
      analysis correcting for 8 covariate risk factors, including the Index for
      Mortality Prediction After Cardiac Transplantation, age, weight, United Network
      for Organ Sharing status, warm and cold ischemia time, repeat sternotomy, and
      pretransplant hematocrit, showed RBC transfusions were independently associated
      with increased length of intensive care unit stay (means ratio = 1.34; 95%
      confidence interval, 1.03-1.76; P = 0.03), and increased inotrope score in the
      first postoperative 24 hour (mean ratio = 1.26; 95% confidence interval, 1.04
      1.52; P = 0.04). Patients suffering major adverse events received significantly
      larger median amounts of blood RBC transfusions (P = 0.002). Transfusions >60
      mL/kg were also associated with increased risk of major adverse events (accuracy
      76%) including postoperative sepsis, extracorporeal membrane oxygenation, open
      chest, dialysis, and graft failure. CONCLUSION: The majority of pediatric
      patients undergoing orthotropic heart transplantation receive RBC transfusions,
      with the largest amount transfused in the operating room. Escalating amounts of
      RBC transfusions are independently associated with increased length of intensive
      care unit stay, inotrope scores, and major adverse events. Since heart allografts
      are a limited resource, improvement in the blood transfusion and conservation
      practices can enhance clinical outcomes in pediatric heart transplant patients.

PMID- 23558833
TI  - Intrathecal pain pump infusions for intractable cancer pain: an algorithm for
      dosing without a neuraxial trial.
AB  - BACKGROUND: Patients with pain from advanced cancer often have limited life
      expectancy. Undergoing an epidural trial for placement of an intrathecal pump in
      these selected patients can exhaust limited days of life. We sought to analyze
      historical data at our cancer center to develop an algorithm to predict initial
      intrathecal pump dosing based on the starting preimplant systemic opioid regimen,
      thus averting an epidural trial and minimizing hospital stay. METHODS: We used
      data pre- and postpump from 46 cancer patients receiving systemic opioids
      undergoing intrathecal pump placement in the last 6 years, all of whom had
      undergone an epidural trial before pump placement. RESULTS: By analyzing
      intrathecal opioid dosage on discharge (in IV morphine equivalents) to age, type
      of pain, cancer type, preimplant opioid dose, and preimplant pain score using
      multiple regression, we created an algorithm that predicts, for cancer patients,
      an appropriate initial dose for an intrathecal pump based on the prepump systemic
      opioid dose, thus avoiding an epidural trial. The predicted value does have a
      broad 95% prediction interval (-122.7% to 147.6%) pointing to the value of a
      trial when feasible. CONCLUSIONS: When an epidural trial is not feasible and an
      intrathecal pump is required in a cancer patient, it is possible to predict an
      initial dose for the intrathecal pump based on the systemic opioid usage. This
      minimizes delays in achieving satisfactory analgesia and discharge to home.

PMID- 23558835
TI  - Echo rounds: Reorientation of an obstructive, hypermobile papillary muscle:
      intraoperative echocardiographic assessment.

PMID- 23558834
TI  - Intraocular pressure in pediatric patients during prone surgery.
AB  - BACKGROUND: Intraoperative intraocular pressure (IOP) in the prone position and
      IOP changes over time have not been evaluated in pediatric surgical patients. We
      sought to determine time-dependent changes in IOP in children undergoing surgery
      in prone position. METHODS: Thirty patients undergoing neurosurgical procedures
      in prone position were included. Using a pulse-mode pneumatonometer, IOP was
      measured in supine position after induction and before emergence of anesthesia
      and in prone position before the start and after the end of surgery. IOP changes
      over time in the prone position were assessed with a linear mixed model (i.e.,
      random slope and intercept model) to adjust for the within-patient correlation.
      RESULTS: IOP in prone position increased by an average of 2.2 mm Hg per hour (P <
      0.001). Sixty-three percent of patients (95% confidence interval [CI], 46%-81%)
      had at least 1 IOP value exceeding 30 mm Hg, and 13% (95% CI, 1%-25%) had at
      least 1 IOP value exceeding 40 mm Hg while prone. Mean IOP increased 7 mm Hg (95%
      CI, 6-9) during the position change from supine to prone (P < 0.001) and
      decreased 10 mm Hg (95% CI, 9-12) after changing the position from prone back to
      supine (P < 0.001). CONCLUSIONS: Changing position from supine to prone
      significantly increases IOP in anesthetized pediatric patients. Moreover, the IOP
      continued to increase during surgery and reached potentially harmful values,
      especially when combined with low mean arterial blood pressures that are common
      during major surgery.

PMID- 23558836
TI  - Color flow Doppler ultrasonography can distinguish caudal epidural injection from
      intrathecal injection.
AB  - BACKGROUND: Color flow Doppler ultrasonography has been used to confirm caudal
      epidural injection, but its ability to detect accidental intrathecal injection is
      unknown. We hypothesized that, when using color flow Doppler, the injection of
      fluid into the epidural space would result in turbulent flow which would appear
      as a burst of color while intrathecal injection would show an absence of a color
      flow Doppler signal. METHODS: Two groups of pediatric patients (up to 6 years of
      age) were prospectively enrolled for this observational study during a 2-month
      period. One group (group E) consisted of patients suitable for elective surgery
      using caudal epidural analgesia, and the other (group I) included patients
      receiving lumbar puncture for intrathecal chemotherapeutic injection. After
      induction of general anesthesia and placement of the patient in the lateral
      position, an 8 MHz curved array probe (Sonosite TITAN, Bothell, WA) was applied
      to obtain a transverse image of the lumbar region (L1-L3). Real-time images using
      color flow Doppler were obtained and recorded during initial injections of 2
      consecutive (20 seconds apart) aliquots of 0.1 mL/kg medication of local
      anesthetic (0.25% bupivacaine) or chemotherapy drugs (mixture of methotrexate,
      cytarabine, and hydrocortisone) at a rate of 0.5 to 1.0 mL/s. After obtaining the
      study images, the rest of the medication was injected in standard fashion. A
      blinded anesthesiologist later evaluated the recorded images to determine a
      positive or negative result (positive = presence of turbulence as illustrated by
      a medley of color; negative = no turbulence or color). Sensitivity, specificity,
      and positive and negative predictive values were calculated for those patients
      who had successful analgesia (group E) and intrathecal (group I) injections.
      RESULTS: Forty recorded images from 41 patients (group E, n = 21; group I, n =
      20) were included in the analysis. The observed sensitivity, specificity,
      positive predictive value, and negative predictive values were all 100%. The
      lower 95% confidence limits were 0.832. CONCLUSION: In the context of this study,
      color flow Doppler could differentiate epidural from intrathecal injection into
      the caudal space of children up to 6 years of age using a 0.1 mL/kg injection
      volume and injection rate of 0.5 to 1.0 mL/s.

PMID- 23558837
TI  - Technical communication: inhaled anesthetic agent-vaporizer mismatch: management
      in settings with limited resources: don't try this at home.
AB  - Agent-specific vaporizers minimize opportunities for error and evidence our
      specialty's commitment to patient safety as a general principle. End-tidal
      anesthetic gas concentration monitoring is a useful adjunct whenever inhaled
      anesthetics are used in operating rooms. Due to their expense and required
      maintenance, end-tidal anesthetic gas monitors are not commonly used in
      developing nations. Unfortunately, in resource-constrained environments,
      situations may arise in which inhaled anesthetic agent-vaporizer mismatch may be
      necessary in the absence of end-tidal anesthetic gas monitoring. Rather than
      merely censure such practice as a threat to safety, we believe that certain
      anesthetic agent-vaporizer mismatch situations can be safely managed providing
      patients with predictable inspired anesthetic gas concentrations while minimizing
      errors. We present an approach based on mathematical models and tested in an
      artificial lung model. Mismatching of inhaled agent and vaporizer is a dangerous
      practice and should not be performed unless it is absolutely necessary. Such
      situations may arise in remote locations where neither end-tidal anesthetic gas
      monitoring nor vaporizer-specific agent is available. We hope our article
      provides guidance in such situations.

PMID- 23558839
TI  - Determinants, associations, and psychometric properties of resident assessments
      of anesthesiologist operating room supervision.
AB  - BACKGROUND: A study by de Oliveira Filho et al. reported a validated set of 9
      questions by which Brazilian anesthesia residents assessed faculty supervision in
      the operating room. The aim of this study was to use this question set to
      determine whether faculty operating room supervision scores were associated with
      residents' year of clinical anesthesia training and/or number of specific
      resident-faculty interactions. We also characterized associations between faculty
      operating room supervision scores and resident assessments of: (1) faculty
      supervision in settings other than operating rooms, (2) faculty clinical ability
      (family choice), and (3) faculty teaching effectiveness. Finally, we
      characterized the psychometric properties of the de Oliveira Filho etal. question
      set in an United States anesthesia residency program. METHODS: All 39 residents
      in the Department of Anesthesia of the University of Iowa in their first (n =
      14), second (n = 13), or third (n = 12) year of clinical anesthesia training
      evaluated the supervision provided by all anesthesia faculty who staffed in at
      least 1 of 3 clinical settings (operating room [n = 49], surgical intensive care
      unit [n = 10], pain clinic [n = 6]). For all resident-faculty pairs, departmental
      billing data were used to quantitate the number of resident-faculty interactions
      and the interval between the last interaction and the assessment. A
      generalizability study was performed to determine the minimum number of resident
      evaluations needed for high reliability and dependability. RESULTS: There were no
      significant associations between faculty mean operating room supervision scores
      and: (1) resident-faculty patient encounters (Kendall taub = 0.01; 95% confidence
      interval [CI], -0.02 to +0.04; P = 0.71), (2) resident-faculty days of
      interaction (taub = -0.01; 95% CI, -0.05 to +0.02; P = 0.46), and (3) days since
      last resident-faculty interaction (taub = 0.01; 95% CI, -0.02 to 0.05; P = 0.49).
      Supervision scores for the operating room and surgical intensive care unit were
      highly correlated (taub = 0.71; 95% CI, 0.63 to 0.78; P < 0.0001). Supervision
      scores for the operating room also were highly correlated with family choice
      scores (taub = 0.77; 95% CI, 0.70 to 0.84; P < 0.0001) and teaching scores (taub
      = 0.87; 95% CI, 0.82 to 0.92; P < 0.0001). High reliability and dependability
      (both G- and phi-coefficients > 0.80) occurred when individual faculty
      anesthesiologists received assessments from 15 or more different residents.
      CONCLUSION: Supervision scores provided by all residents can be given equal
      weight when calculating an individual faculty anesthesiologist's mean supervision
      score. Assessments of supervision, teaching, and quality of clinical care are
      highly correlated. When the de Oliveira Filho et al. question set is used in a
      United States anesthesia residency program, supervision scores are highly
      reliable and dependable when at least 15 residents assess each faculty.

PMID- 23558838
TI  - Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible
      population of the United States.
AB  - BACKGROUND: Mutations in the ryanodine receptor type 1 gene (RYR1) that encodes
      the skeletal muscle-specific intracellular calcium (Ca(2+)) release channel are a
      cause of malignant hyperthermia (MH). In this study, we examined RYR1 mutations
      in a large number of North American MH-susceptible (MHS) subjects without prior
      genetic diagnosis. METHODS: RYR1 was examined in 120 unrelated MHS subjects from
      the United States in a tiered manner. The alpha-1 subunit of the dihydropyridine
      receptor gene (CACNA1S) was screened for 4 variants in subjects in whom no
      abnormality was found in >= 100 exons of RYR1. RESULTS: Ten known causative MH
      mutations were found in 26 subjects. Variants of uncertain significance in RYR1
      were found in 36 subjects, 16 of which are novel. Novel variants in both RYR1 and
      CACNA1S were found in the 1 subject who died of MH. Two RYR1 variants were found
      in 4 subjects. Variants of uncertain significance were found outside and inside
      the hotspots of RYR1. Maximal contractures in the caffeine-halothane contracture
      test were greater in those who had a known MH mutation or variant of uncertain
      significance in RYR1 than in those who did not. CONCLUSIONS: The identification
      of novel RYR1 variants and previously observed RYR1 variants of uncertain
      significance in independent MHS families is necessary for demonstrating the
      significance of these variants for MH susceptibility and supports the need for
      functional studies of these variants. Continued reporting of the clinical
      phenotypes of MH is necessary for interpretation of genetic findings, especially
      because the pathogenicity of most of these genetic variants associated with MHS
      remains to be elucidated.

PMID- 23558840
TI  - The hyperglycemic response to major noncardiac surgery and the added effect of
      steroid administration in patients with and without diabetes.
AB  - BACKGROUND: The pattern and magnitude of the hyperglycemic response to surgical
      stress, the added effect of low-dose steroids, and whether these differ in
      diabetics and nondiabetics remain unclear. We therefore tested 2 hypotheses: (1)
      that diabetics show a greater increase from preoperative to intraoperative
      glucose concentrations than nondiabetics; and (2) that steroid administration
      increases intraoperative hyperglycemia more so in diabetics compared with
      nondiabetics. METHODS: Patients scheduled for major noncardiac surgery under
      general anesthesia were enrolled and randomized to preoperative IV 8 mg
      dexamethasone or placebo, stratified by diagnosis of diabetes. Patients were part
      of a larger underlying trial (the Dexamethasone, Light Anesthesia and Tight
      Glucose Control [DeLiT] Trial). IV insulin was given when glucose concentration
      exceeded 215 mg/dL. The primary outcome measure was the change in glucose from
      the preoperative to maximal intraoperative glucose concentration. We also report
      the time-dependent pattern of intraoperative hyperglycemia. RESULTS: Ninety
      patients (23% with diabetes) were randomized to dexamethasone, and 95 (29% with
      diabetes) were given placebo. The mean +/- SD change from preoperative to maximal
      intraoperative glucose concentration was 63 +/- 69 mg/dL in diabetics and 72 +/-
      45 mg/dL in nondiabetics. The mean covariable-adjusted change (95% confidence
      interval) in nondiabetics was 29 (13, 46) mg/dL more than in diabetics (P <
      0.001). For all patients combined, mean glucose increased slightly from
      preoperative to incision, substantially from incision to surgery midpoint, and
      then remained high and fairly stable through emergence, with nondiabetic patients
      showing a greater increase (P < 0.001). For nondiabetics, the mean increase in
      glucose concentration (97.5% CI) was 29 (9, 49) mg/dL more in patients given
      dexamethasone than placebo (P = 0.0012). However, there was no dexamethasone
      effect in diabetics (P = 0.99). CONCLUSIONS: Treatment of intraoperative
      hyperglycemia should account for the hyperglycemic surgical stress response trend
      depending on the stage of surgery as well as the added effects of steroid
      administration. Denying steroid prophylaxis for postoperative nausea and vomiting
      for fear of hyperglycemic response should be reconsidered given the limited
      effect of steroids on intraoperative blood glucose concentrations.

PMID- 23558842
TI  - Echo didactics: a comparison of basic transthoracic and transesophageal
      echocardiography views in the perioperative setting.

PMID- 23558841
TI  - An alternative distal approach for the lumbar medial branch radiofrequency
      denervation: a prospective randomized comparative study.
AB  - BACKGROUND: An alternative technique involving a "distal approach" can be used
      for lumbar medial branch radiofrequency denervation (LMBRFD). We described and
      assessed this technique by comparing it with a conventional tunnel vision
      approach in a prospective randomized trial. METHODS: Eighty-two patients
      underwent LMBRFD by a distal (n = 41) or a tunnel vision approach (n = 41). The
      primary end point was a comparison of the mean difference in the change of 11
      point numeric rating scale (NRS) scores of low back pain from entry to the scores
      at 1 month (NRS at baseline--NRS at 1 month) and at 6 months (NRS at baseline-
      NRS at 6 months) between the distal approach group and the tunnel vision approach
      group. The secondary end points were a change of NRS and the Oswestry disability
      index over time. RESULTS: Thirty-four patients in each group had complete time
      courses. There were no statistically significant differences in the change of NRS
      scores between the groups at 1 month (corrected P = 0.19; 97.5% 2-sided
      confidence interval [CI], -1.37 to 0.37) and 6 months (corrected P = 0.53; 97.5%
      CI, -1.36 to 0.77). Patients in both groups showed a statistically significant
      reduction in NRS and Oswestry disability index scores from baseline to that of
      the scores at 1 and 6 months (all P < 0.0001, Bonferroni corrected). The
      procedure-related pain score was significantly lower in the distal approach group
      (P = 0.001; 99% CI, -2.00 to -0.23). CONCLUSIONS: Patients who underwent LMBRFD
      by the tunnel vision or distal approaches showed significant pain relief at the 6
      month follow-up. Less periprocedural pain was reported in the distal approach
      group. We consider that the distal approach provides an improved option for
      LMBRFD.

PMID- 23558843
TI  - Brief report: perioperative analgesic efficacy and plasma concentrations of S+ 
      ketamine in continuous epidural infusion during thoracic surgery.
AB  - BACKGROUND: In our study, we evaluated the analgesic effect and plasma level time
      course of subanesthetic doses of intraoperative S(+)-ketamine administered by
      continuous epidural infusion for postthoracotomic pain. METHODS: A study
      population of 140 patients undergoing thoracic surgery was randomly assigned to
      either S(+)-ketamine or ropivacaine by continuous epidural infusion. The outcome
      measures were as follows: (a) intraoperative fentanyl requirements; (b)
      postoperative pain intensity; and (c) postoperative rescue analgesics. RESULTS:
      Intraoperative fentanyl consumption was significantly lower (median of
      difference: -58.6 MUg; 95% confidence interval [CI], -97.2 to -19.6 MUg; P =
      0.0032) in patients in the ketamine group than those in the ropivacaine group.
      Postoperative visual analog scale scores were significantly lower in the ketamine
      group than in controls (Wilcoxon-Mann-Whitney odds at 24 hours = 6.25; 95% CI,
      4.07 to 1.97; P < 0.0001). Rescue analgesics were required more frequently in
      controls than in the ketamine group (percentage difference: 58.6%; 95% CI, 43.3%
      to 69.6%; P < 0.0001). The mean plasma level of ketamine declined rapidly during
      continuous epidural infusion and decayed slowly after it had stopped.
      CONCLUSIONS: Our data show that epidural infusion of subanesthetic doses of S(+)
      ketamine during thoracic surgery provides better postoperative analgesia than
      epidural ropivacaine.

PMID- 23558844
TI  - Estimating surgical case durations and making comparisons among facilities:
      identifying facilities with lower anesthesia professional fees.
AB  - Consumer-driven health care relies on transparency in cost estimates for surgery,
      including anesthesia professional fees. Using systematic narrative review, we
      show that providing anesthesia costs requires that each facility (anesthesia
      group) estimate statistics, reasonably the mean and the 90% upper prediction
      limit of case durations by procedure. The prediction limits need to be
      calculated, for many procedures, using Bayesian methods based on the log-normal
      distribution. Insurers and/or governments lack scheduled durations and procedures
      and cannot practically infer these estimates because of the large heterogeneities
      among facilities in the means and coefficients of variation of durations.
      Consequently, the insurance industry cannot provide the cost information
      accurately from public and private databases. Instead, the role of insurers
      and/or governments can be to identify facilities with significantly briefer
      durations (costs to the patient) than average. Such comparisons of durations
      among facilities should be performed with correction for the effects of the
      multiple comparisons. Our review also has direct implications to the potentially
      more important issue of how to study the association between anesthetic durations
      and patient morbidity and mortality. When pooling duration data among facilities,
      both the large heterogeneity in the means and coefficients of variation of
      durations among facilities need to be considered (e.g., using "multilevel" or
      "hierarchical" models).

PMID- 23558845
TI  - Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of
      lactation.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are available as
      "over-the counter" medications in most countries, are widely used by both
      pregnant and lactating women. They are popular non-opioid analgesics for the
      treatment of pain after vaginal and operative delivery. In addition, NSAIDs are
      used for tocolysis in premature labor, and low-dose aspirin has a role in the
      prevention of preeclampsia and recurrent miscarriage in antiphospholipid
      syndrome. NSAIDs and aspirin may affect fertility and increase the risk of early
      pregnancy loss. In the second trimester their use is considered reasonably safe,
      but has been associated with fetal cryptorchism. In the third trimester, NSAIDs
      and aspirin are usually avoided because of significant fetal risks such as renal
      injury, oligohydramnios, constriction of the ductus arteriosus (with potential
      for persistent pulmonary hypertension in the newborn), necrotizing enterocolitis,
      and intracranial hemorrhage. Maternal administration or ingestion of most NSAIDs
      results in low infant exposure via breastmilk, such that both cyclooxygenase-1
      and cyclooxygenase-2 inhibitors are generally considered safe, and preferable to
      aspirin, when breastfeeding.

PMID- 23558846
TI  - Validation of a measurement tool for self-assessment of teamwork in intensive
      care.
AB  - BACKGROUND: Teamwork is an important contributor to patient safety and a
      validated teamwork measurement tool could help healthcare teams identify areas
      for improvement and measure progress. We explored the psychometric properties of
      a teamwork measurement tool when used for self-assessment. We hypothesized that
      the tool had a valid factor structure and that scores from participants and
      external assessors would correlate. METHODS: Forty intensive care teams (one
      doctor, three nurses) participated in four simulated emergencies, and each
      independently rated their team's performance at the end of each case using the
      teamwork measurement tool, without prior training in the use of the tool. We used
      exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and
      compared factor structure between participants and external assessors (using
      previously reported data). Scores from participants and external assessors were
      compared using Pearson's correlation coefficient. RESULTS: EFA demonstrated items
      loaded onto three distinct factors which were supported by the CFA. We found
      significant correlations between external and participant scores for overall
      teamwork scores and the three factors. Participants agreed with external
      assessors on the ranking of overall team performance but scored themselves
      significantly higher than external assessors. CONCLUSIONS: The teamwork
      measurement tool has a valid structure when used for self-assessment. Participant
      and external assessor scores correlated significantly, suggesting that
      participants could discriminate between different levels of performance, although
      leniency in self-assessed scores indicated the need for calibration. This tool
      could help structure reflection on teamwork and potentially facilitate self
      directed, workplace-based improvement in teamwork.

PMID- 23558847
TI  - Implementation science: implications for intervention research in hospice and
      palliative care.
AB  - This article provides a general introduction to implementation science-the
      discipline that studies the implementation process of research evidence-in the
      context of hospice and palliative care. By discussing how implementation science
      principles and frameworks can inform the design and implementation of
      intervention research, we aim to highlight how this approach can maximize the
      likelihood for translation and long-term adoption in clinical practice settings.
      We present 2 ongoing clinical trials in hospice that incorporate considerations
      for translation in their design and implementation as case studies for the
      implications of implementation science. This domain helps us better understand
      why established programs may lose their effectiveness over time or when
      transferred to other settings, why well-tested programs may exhibit unintended
      effects when introduced in new settings, or how an intervention can maximize cost
      effectiveness with strategies for effective adoption. All these challenges are of
      significance to hospice and palliative care, where we seek to provide effective
      and efficient tools to improve care services. The emergence of this discipline
      calls for researchers and practitioners to carefully examine how to refine
      current and design new and innovative strategies to improve quality of care. 

PMID- 23558848
TI  - Structural peculiarities of configurational isomers of 1-styrylpyrroles according
      to 1N, 13S and 15N NMR spectroscopy and density functional theory calculations:
      electronic and steric hindrance for planar structure.
AB  - Comparative analysis of the (1)N and (13)S NMR data for a series of the E and Z-1
      styrylpyrroles, E and Z-1-(1-propenyl)pyrroles, 1-vinylpyrroles and styrene
      suggests that the conjugation between the unsaturated fragments in the former
      compounds is reduced. This is the result of the mutual influence of the donor p
      pi and pi-pi conjugation having opposite directions. According to the NMR data
      combined with the density functional theory calculations, the Z isomer of 1
      styrylpyrrole has essentially a nonplanar structure because of the steric
      hindrance. However, the E isomer of 1-styrylpyrrole is also an out-of-plane
      structure despite the absence of a sterical barrier for the planar one. Deviation
      of the E isomer from the planar structure seems to be caused by an electronic
      hindrance produced by a mutual influence of the p-pi and pi-pi conjugation. The
      structure of the E isomer of the 2-substituted 1-styrylpyrroles is similar to
      that of the 2-substituted 1-vinylpyrroles. The steric effects in the Z isomer of
      the 2-substituted 1-styrylpyrroles result in the large increase of the dihedral
      angle between planes of the pyrrole ring and double bond.

PMID- 23558849
TI  - Experiences of crisis pregnancy among Irish and non-Irish adults living in
      Ireland: findings from the Irish Contraception and Crisis Pregnancy Survey 2010
      (ICCP-2010).
AB  - BACKGROUND: Using nationally representative data, this paper investigates the
      experience of crisis pregnancy (CP) among Irish and non-Irish adults living in
      Ireland in 2010. AIMS: To generate a detailed profile of Irish and non-Irish
      adults living in Ireland who have had an experience of CP and to investigate the
      differences in the experiences of CP between Irish and non-Irish adults. METHOD:
      A national cross-sectional telephone survey methodology recruited 3,002 adult (18
      45 years) participants (69 % response). Descriptive statistics and Chi-square
      analysis were used to compare the differences between the Irish (n = 334) and non
      Irish sample (n = 57) with an experience of CP. RESULTS: The majority of
      respondents with an experience of CP had a higher education level and were aged
      between 18 and 25 years. Significant differences, in terms of outcome of CP, were
      also found between groups; with more Irish respondents choosing parenthood over
      abortion, compared with their non-Irish counterparts. CONCLUSION: This paper
      presents a unique profile of Irish and non-Irish adults living in Ireland with an
      experience of CP. Enhanced promotion of longer-acting contraceptives to all
      younger adults, and targeted awareness raising of post-abortion services among
      the non-Irish community, is recommended.

PMID- 23558850
TI  - Automated quantification of budding Saccharomyces cerevisiae using a novel image
      cytometry method.
AB  - The measurements of concentration, viability, and budding percentages of
      Saccharomyces cerevisiae are performed on a routine basis in the brewing and
      biofuel industries. Generation of these parameters is of great importance in a
      manufacturing setting, where they can aid in the estimation of product quality,
      quantity, and fermentation time of the manufacturing process. Specifically,
      budding percentages can be used to estimate the reproduction rate of yeast
      populations, which directly correlates with metabolism of polysaccharides and
      bioethanol production, and can be monitored to maximize production of bioethanol
      during fermentation. The traditional method involves manual counting using a
      hemacytometer, but this is time-consuming and prone to human error. In this
      study, we developed a novel automated method for the quantification of yeast
      budding percentages using Cellometer image cytometry. The automated method
      utilizes a dual-fluorescent nucleic acid dye to specifically stain live cells for
      imaging analysis of unique morphological characteristics of budding yeast. In
      addition, cell cycle analysis is performed as an alternative method for budding
      analysis. We were able to show comparable yeast budding percentages between
      manual and automated counting, as well as cell cycle analysis. The automated
      image cytometry method is used to analyze and characterize corn mash samples
      directly from fermenters during standard fermentation. Since concentration,
      viability, and budding percentages can be obtained simultaneously, the automated
      method can be integrated into the fermentation quality assurance protocol, which
      may improve the quality and efficiency of beer and bioethanol production
      processes.

PMID- 23558851
TI  - Regulation of intracellular pH by glycosaminoglycans.
AB  - The intracellular pH is regulated by a delicate balance of ion distribution
      across the plasma membrane and the physico-chemical properties of intra- and
      extracellular components. We analyzed the effects of glycosaminoglycans on the
      intracellular pH of fibroblasts by using the fluorescent pH indicator BCECF-AM.
      Addition of hyaluronan, hyaluronan oligosaccharides, chondroitin sulfate, or
      heparin to the culture medium of fibroblasts caused intracellular acidification
      from pH 7.2 to 6.7 in a concentration dependent manner. High molecular weight
      hyaluronan acidified more than hyaluronan oligosaccharides at the same
      concentrations. Hyaluronidase treatment or inhibition of hyaluronan export with
      xanthohumol led to intracellular alkalization. These observations indicated that
      extracellular glycosaminoglycans participate in intracellular pH regulation. The
      mechanism was explained by Donnan effects and molecular crowding.

PMID- 23558852
TI  - Biomarkers of exposure in Monday morning urine samples as a long-term measure of
      exposure to aromatic diisocyanates.
AB  - PURPOSE: Exposure to diisocyanates is a known occupational hazard. One method for
      monitoring occupational exposure is by analyzing biomarkers in hydrolyzed urine
      and plasma. The half-life of the biomarkers in plasma is about 3 weeks, and the
      urinary elimination is divided into one fast (hours) and one slow phases (weeks).
      Polymorphism in glutathione S-transferase enzymes (GST) is earlier shown to
      modify the metabolism. The aim of the study was to assess whether biomarkers of
      exposure in urine collected after two non-exposed days correlate with levels in
      plasma and whether they can be used as a measure for long-term exposure to
      aromatic diisocyanates and further whether polymorphisms in GST influenced the
      correlations. METHODS: Biomarkers of exposure was analyzed in urine and blood
      samples collected from 24 workers, exposed to at least one of toluene-,
      methylenediphenyl- or naphthalene diisocyanate, on a Monday morning after at
      least two unexposed days. Moreover, genotype was determined for 19 of the
      workers. RESULTS: The corresponding specific gravity-adjusted biomarkers in urine
      and plasma levels for the different diisocyanates correlated well (r between
      0.689 and 0.988). When taking all samples together, the correlation coefficient
      was 0.926. Polymorphism in the GSTM1 genotype seemed to modify the association.
      CONCLUSION: Urine collected after two unexposed days can possibly be used as long
      term biomarker of exposure for aromatic diisocyanates.

PMID- 23558853
TI  - Argyrophil cell density in the oxyntic mucosa is higher in female than in male
      morbidly obese patients.
AB  - Obesity is a multifactorial disorder often associated with many important
      diseases such as diabetes, hypertension and other metabolic syndrome conditions.
      Argyrophil cells represent almost the total population of endocrine cells of the
      human gastric mucosa and some reports have described changes of specific types of
      these cells in patients with obesity and metabolic syndrome. The present study
      was designed to evaluate the global population of argyrophil cells of the gastric
      mucosa of morbidly obese and dyspeptic non-obese patients. Gastric biopsies of
      antropyloric and oxyntic mucosa were obtained from 50 morbidly obese patients
      (BMI >40) and 50 non-obese patients (17 dyspeptic overweight and 33 lean
      individuals) and processed for histology and Grimelius staining for argyrophil
      cell demonstration. Argyrophil cell density in the oxyntic mucosa of morbidly
      obese patients was higher in female (238.68 +/- 83.71 cells/mm(2)) than in male
      patients (179.31 +/- 85.96 cells/mm(2)) and also higher in female (214.20 +/-
      50.38 cells/mm(2)) than in male (141.90 +/- 61.22 cells/mm(2)) morbidly obese
      patients with metabolic syndrome (P = 0.01 and P = 0.02, respectively). In
      antropyloric mucosa, the main difference in argyrophil cell density was observed
      between female morbidly obese patients with (167.00 +/- 69.30 cells/mm(2)) and
      without (234.00 +/- 69.54 cells/mm(2)) metabolic syndrome (P = 0.001). In
      conclusion, the present results show that the number of gastric argyrophil cells
      could be under gender influence in patients with morbid obesity. In addition,
      gastric argyrophil cells seem to behave differently among female morbidly obese
      patients with and without metabolic syndrome.

PMID- 23558854
TI  - Impairment of locomotor activity induced by the novel N-acylhydrazone derivatives
      LASSBio-785 and LASSBio-786 in mice.
AB  - The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine
      (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were
      prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294).
      The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system
      activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30
      mg/kg, ip) reduced locomotor activity from 209 +/- 26 (control) to 140 +/- 18 (P
      < 0.05) or 146 +/- 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or
      30 mg/kg, iv) also reduced locomotor activity from 200 +/- 15 to 116 +/- 29 (P <
      0.05) or 60 +/- 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786
      (15 or 30 mg/kg, iv) reduced locomotor activity from 200 +/- 15 to 127 +/- 10 (P
      < 0.01) or 96 +/- 14 crossings/min (P < 0.01), respectively. Pretreatment with
      flumazenil (20 mg/kg, ip) prevented the locomotor impairment induced by NAH
      analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ)
      receptor is involved. This finding was supported by the structural similarity of
      NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ
      receptor. LASSBio-785 or LASSBio-786 (30 mg/kg, ip, n = 10) increased
      pentobarbital-induced sleeping time from 42 +/- 5 (DMSO) to 66 +/- 6 (P < 0.05)
      or 75 +/- 4 min (P < 0.05), respectively. The dose required to achieve 50%
      hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or
      9.5 mg/kg, respectively. These data suggest that both NAH analogues might be
      useful for the development of new neuroactive drugs for the treatment of insomnia
      or for use in conjunction with general anesthesia.

PMID- 23558855
TI  - Phytohemagglutinin improves the development and ultrastructure of in vitro
      cultured goat (Capra hircus) preantral follicles.
AB  - The objective this study was to determine the effect of phytohemagglutinin (PHA)
      on survival, growth and gene expression in caprine secondary follicles cultured
      in vitro. Secondary follicles (~0.2 mm) were isolated from the cortex of caprine
      ovaries and cultured individually for 6 days in alpha-MEM+ supplemented with PHA
      (0, 1, 10, 50, 100, or 200 ug/mL). After 6 days of culture, follicle diameter and
      survival, antrum formation, ultrastructure and expression of mRNA for FSH
      receptors (FSH-R), proliferating cell nuclear antigen (PCNA), and neuronal nitric
      oxide synthase were determined. All treatments maintained follicular survival
      [alpha-MEM+ (94.59%); 1 ug/mL PHA (96.43%); 10 ug/mL PHA (84.85%); 50 ug/mL PHA
      (85.29%); 100 ug/mL PHA (88.57%), and 200 ug/mL PHA (87.50)], but the presence of
      10 ug/mL PHA in the culture medium increased the antrum formation rate (21.21%)
      when compared with control (5.41%, P < 0.05) and ensured the maintenance of
      oocyte and granulosa cell ultrastructures after 6 days of culture. The expression
      of mRNA for FSH-R (2.7 +/- 0.1) and PCNA (4.4 +/- 0.2) was also significantly
      increased in follicles cultured with 10 ug/mL PHA in relation to those cultured
      in alpha-MEM+ (1.0 +/- 0.1). In conclusion, supplementation of culture medium
      with 10 ug/mL PHA maintains the follicular viability and ultrastructure, and
      promotes the formation of antral cavity after 6 days of culture in vitro.

PMID- 23558856
TI  - Rat vas deferens SERCA2 is modulated by Ca2+/calmodulin protein kinase II
      mediated phosphorylation.
AB  - Ca2+ pumps are important players in smooth muscle contraction. Nevertheless,
      little information is available about these pumps in the vas deferens. We have
      determined which subtype of sarco(endo)plasmic reticulum Ca2+-ATPase isoform
      (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin
      (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca2+-ATPase from a
      membrane fraction containing the highest SERCA levels in the RVD homogenate has
      the same molecular mass (~115 kDa) as that of SERCA2 from the rat cerebellum. It
      has a very high affinity for Ca2+ (Ca0.5 = 780 nM) and a low sensitivity to
      vanadate (IC50 = 41 uM). These facts indicate that SERCA2 is present in the RVD.
      Immunoblotting for CaM and Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      showed the expression of these two regulatory proteins. Ca2+ and CaM increased
      serine-phosphorylated residues of the 115-kDa protein, indicating the involvement
      of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is
      accompanied by an 8-fold increase of thapsigargin-sensitive Ca2+ accumulation in
      the lumen of vesicles derived from these membranes. These data establish that
      SERCA2 in the RVD is modulated by Ca2+ and CaM, possibly via CaMKII, in a process
      that results in stimulation of Ca2+ pumping activity.

PMID- 23558857
TI  - Comparison of the neurobiological effects of attribution retraining group therapy
      with those of selective serotonin reuptake inhibitors.
AB  - The aim of this study was to compare the effectiveness of attribution retraining
      group therapy (ARGT) with selective serotonin reuptake inhibitors (SSRIs) in the
      treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD),
      and obsessive-compulsive disorder (OCD). Subjects were sequentially recruited and
      randomized into two groups, one receiving ARGT (n = 63) and the other SSRIs (n =
      66) for 8 weeks. Fifty-four ARGT outpatients with MDD (n = 19), GAD (n = 19), and
      OCD (n = 16) and 55 SSRI outpatients with MDD (n = 19), GAD (n = 19), and OCD (n
      = 17) completed the study. All subjects were assessed using the Hamilton
      Depression Scale and Hamilton Anxiety Scale before and after treatment. The 10
      item Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects.
      Plasma levels of serotonin, norepinephrine, cortisol, and adrenocorticotropic
      hormone were also measured at baseline and 8 weeks after completion of treatment.
      Symptom scores were significantly reduced (P < 0.001) in both the ARGT and SSRI
      groups at the end of treatment. However, MDD, GAD and OCD patients in the ARGT
      group had significantly lower plasma cortisol concentrations compared to baseline
      (P < 0.05), whereas MDD and OCD patients receiving SSRIs showed significantly
      increased plasma levels of serotonin (P < 0.05). These findings suggest that ARGT
      may modulate plasma cortisol levels and affect the hypothalamus-pituitary-adrenal
      axis as opposed to SSRIs, which may up-regulate plasma serotonin levels via a
      different pathway to produce an overall improvement in the clinical condition of
      the patients.

PMID- 23558858
TI  - Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with
      cyanotic congenital heart disease.
AB  - Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13
      activity (the metalloprotease that cleaves VWF physiologically) have been
      reported in several cardiovascular disorders with prognostic implications. We
      therefore determined the level of these proteins in the plasma of children with
      cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty
      eight children were enrolled (age 0.83 to 7.58 years). Measurements were
      performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and
      Western blotting were used to estimate antigenic and biological activities, and
      proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were
      decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 +/
      24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High
      molecular weight VWF multimers were not related, suggesting an interaction of VWF
      with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS
      13 activity, a longer activated partial thromboplastin time and the need for
      cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05).
      Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag
      (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an
      increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and
      postoperative median values, P = 0.0029). ADAMTS-13 consumption was further
      confirmed by decreased ADAMTS-13 antigenic concentration (0.91 +/- 0.30 to 0.70
      +/- 0.25 ug/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We
      conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme
      consumption, associated with abnormal structure and function of VWF.

PMID- 23558859
TI  - Chromogenic in situ hybridization compared with other approaches to evaluate
      HER2/neu status in breast carcinomas.
AB  - Human epidermal growth factor receptor 2 (HER2) has been evaluated in breast
      cancer patients to identify those most likely to benefit from herceptin-targeted
      therapy. HER2 amplification, detected in 20-30% of invasive breast tumors, is
      associated with reduced survival and metastasis. The most frequently used
      technique for evaluating HER2 protein status as a routine procedure is
      immunohistochemistry (IHC). HER2 copy number alterations have also been evaluated
      by fluorescence in situ hybridization (FISH) in moderate immunoexpression (IHC
      2+) cases. An alternative procedure to evaluate gene amplification is chromogenic
      in situ hybridization (CISH), which has some advantages over FISH, including the
      correlation between HER2 status and morphological features. Other methodologies
      have also been used, such as silver-enhanced in situ hybridization (SISH) and
      quantitative real-time RT-PCR, to determine the number of HER2 gene copies and
      expression, respectively. Here we will present a short and comprehensive review
      of the current advances concerning HER2 evaluation in human breast cancer.

PMID- 23558860
TI  - Electroretinography in dogs using a fiber electrode prototype.
AB  - We compared two electroretinography (ERG) electrodes in dogs using ERG standards
      of the International Society for Clinical Electrophysiology of Vision (ISCEV).
      Ten healthy Yorkshire terrier dogs (mean age, 2.80 +/- 1.42 years; 6 females)
      weighing 5.20 +/- 1.56 kg were evaluated using an ERG system for veterinary use.
      Dark- and light-adapted ERG responses were recorded using an ERG-Jet electrode
      and a fiber electrode prototype. The examinations were performed during 2 visits,
      3 weeks apart. Both electrodes (ERG-Jet or fiber prototype) were used on each
      animal and the first eye to be recorded (OD * OS) was selected randomly. Three
      weeks later the examination was repeated on the same animal switching the type of
      electrode to be used that day and the first eye to be examined. The magnitude and
      waveform quality obtained with the two electrode types were similar for all ERG
      responses. ERG amplitudes and implicit times obtained from dogs using the fiber
      electrode prototype were comparable to those obtained with the ERG-Jet electrode
      for rod, maximal rod-cone summed, cone, and 30-Hz flicker responses. The fiber
      electrode prototype is a low-cost device, available as an alternative instrument
      for clinical veterinary ERG recording for retinal function assessment.

PMID- 23558861
TI  - AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric
      cancer cells.
AB  - Hyperthermia is one of the most effective adjuvant treatments for various cancers
      with few side effects. However, the underlying molecular mechanisms still are not
      known. N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, has been
      shown to be involved in diverse cellular stresses including hypoxia,
      lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to
      progression of gastric cancer. In the current study, our data showed that the
      apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after
      treatment with hyperthermia (42 degrees C for 1 h) compared to 5.1% in control
      cells (P < 0.05). Nevertheless, there was no obvious change in the expression
      level of total Ndrg2 during this process. Further investigation demonstrated that
      the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to
      3.2- and 1.9-fold (hyperthermia group vs control group) at 3 h in MKN28 cells,
      respectively (P < 0.05). We also found that heat treatment significantly
      increased AKT phosphorylation. AKT inhibitor VIII (10 uM) decreased the
      phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the
      apoptosis rate rose significantly in MKN28 cells (16.4%) treated with a
      combination of AKT inhibitor VIII and hyperthermia compared to that (6.8%) of
      cells treated with hyperthermia alone (P < 0.05). Taken together, these data
      demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an
      AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII
      suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to
      apoptosis induced by hyperthermia.

PMID- 23558863
TI  - Infection of primary hepatocytes with adenoviral vectors alters biliary lipid
      metabolism.
AB  - In the context of a study of the involvement of SND1 (also known as coactivator
      p100) in biliary lipid secretion by primary rat hepatocytes, first-generation
      adenoviral vectors were used to promote the overexpression and underexpression of
      the protein SND1. Although differential expression of SND1 did not result in
      significant changes in the processes studied, some effects of the adenoviral
      infection itself were observed. In particular, infected hepatocytes showed a
      higher intracellular taurocholate accumulation capacity. Additionally, small
      heterodimer partner (SHP) and farnesoid X receptor (FXR), which are nuclear
      receptors essential for the regulation of bile salt metabolism and transport,
      were underregulated at the mRNA level. Our results suggest that adenoviral
      vectors could be altering some important control mechanism and indicate that
      adenoviral vectors should be used with caution as transfection vectors for
      hepatocytes when biliary lipid metabolism is to be studied.

PMID- 23558862
TI  - Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients
      with colorectal and metastatic colorectal cancer.
AB  - The objective of the present study was to investigate the effect of leptin on the
      progression of colorectal carcinoma to metastatic disease by analyzing the serum
      leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue
      samples were obtained from 31 patients who underwent surgical resection for colon
      (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was
      determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA
      expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA
      data were analyzed by the Student t-test and RT-PCR data were analyzed by the
      Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in
      human metastatic colorectal cancer was higher than in local colorectal cancer
      tissues. On the other hand, mean serum leptin concentration was significantly
      higher in local colorectal cancer patients compared to patients with metastatic
      colorectal cancer. The results of the present study suggest a role for leptin in
      the progression of colon cancer to metastatic disease without weight loss. In
      other words, significantly increased Ob-R mRNA expression and decreased serum
      leptin concentration in patients with metastatic colon cancer indicate that
      sensitization to leptin activity may be a major indicator of metastasis to the
      colon tissue and the determination of leptin concentration and leptin gene
      expression may be used to aid the diagnosis.

PMID- 23558864
TI  - Expanding the role of NCCT in acute stroke imaging: thrombus length measurement
      and its potential impact on current practice.

PMID- 23558866
TI  - From the countries of famous cavalry and famous gauchos: smooth transition to the
      international world of cardiology.

PMID- 23558865
TI  - Salvage of distal non-target coil embolization with stent placement and
      intravenous eptifibatide in a ruptured, unsecured, atypical aneurysm.
AB  - INTRODUCTION: Small aneurysms may be challenging to embolize. In cases of
      subarachnoid hemorrhage (SAH) where treatment is delayed, physicians may have to
      balance the risks of certain required therapies (antiplatelet agents) with the
      risk of rerupture. We describe a case of a technically challenging anterior
      cerebral artery aneurysm requiring eptifibatide infusion prior to definitive
      aneurysm treatment. CASE REPORT: A 57-year-old woman with SAH, underwent coil
      embolization of a small fenestrated A1-A2 junction aneurysm. The procedure was
      complicated by downstream coil migration which was then treated with Enterprise
      stent placement in the pericallosal artery. This required subsequent infusion of
      a glycoprotein IIb/IIIa inhibitor until the aneurysm could be repaired
      surgically. CONCLUSIONS: Revascularization with a stent in a distal cerebral
      vessel may salvage inadvertent coil migration. Although it is undesirable to
      administer antiplatelet agents to patients with SAH, in these circumstances short
      acting agents may be used.

PMID- 23558867
TI  - Blood pressure variability: epidemiological and clinical issues.
AB  - Blood pressure variability (BPV) is a classical physiological phenomenon. This
      paper describes major epidemiological and clinical issues of BPV which may be
      important to understand the background of this interesting feature. In healthy
      subjects, BPV is a measure of hemodynamic condition and refl ects function of
      autonomic nervous system. BP fl uctuations result from the complex interaction
      between environmental stimulation, genetic factors and cardiovascular control
      mechanisms. Abnormal BPV is recognized in persons with a blurred dipping pattern
      (i.e. extreme dipping, non-dipping, reverse-dipping, morning surge of BP) or
      increased variations of day-time or night-time BP (high BP lability).
      Inappropriate BPV worsens the outcome, including increase in all-cause and
      cardiac mortality and incidence of cardiovascular events, and advance in target
      organ damage. Abnormal BPV may be softened or removed with suitable time
      dependent administration of anti-hypertensive agents, especially those acting on
      the renin-angiotensin system.

PMID- 23558868
TI  - Congenital heart defects in Kabuki syndrome.
AB  - BACKGROUND: Kabuki syndrome (KS) is an entity of multiple congenital
      malformations with mental retardation with undetermined etiology. Congenital
      heart defects are one of the clinical manifestations of KS with insufficient
      elucidations. METHODS: Literature of congenital heart defects associated with KS
      was comprehensively retrieved, collected and reviewed. The clinical features of
      the congenital heart defects in the patients with KS were summarized. RESULTS:
      Congenital heart defects were one of the clinical manifestations of KS with 90.6%
      of the patients being diagnosed prenatally or at an early age. Left-sided
      obstructions/aortic dilation and septal defects were the fi rst two types of
      anomalies, accounting up to 46.1% and 32.9%, respectively. The most common
      congenital heart defects were coarctation of the aorta, and atrial and
      ventricular septal defects. Fifteen (19.7%) patients received surgical repair of
      congenital heart defects at a mean age of 0.8 +/- 1.3 years. CONCLUSIONS:
      Congenital heart defects are one of the clinical manifestations of KS with 90.6%
      of the patients being diagnosed prenatally or at an early age. About 20% of the
      patients warranted surgical repair of the heart defects. Patients with KS require
      close follow-up in terms of their etiology, clinical presentations and long-term
      prognosis.

PMID- 23558869
TI  - Risk factors for bleeding complications in patients undergoing transcatheter
      aortic valve implantation (TAVI).
AB  - BACKGROUND: The risk of bleedings in transcatheter aortic valve implantation
      (TAVI) patients increases due to age and concomitant diseases. The aim of the
      study was to assess the risk of bleedings, their influence on early prognosis of
      TAVI patients and utility of the TIMI and GUSTO scales in the evaluation of
      bleeding and in prediction of blood transfusion. METHODS: This was a single
      center study of in-hospital bleedings in 56 consecutive TAVI patients. Bleedings
      were classified according to the GUSTO and TIMI scales. HASBLED's scale risk
      factors, diabetes mellitus, female sex, the route of bioprosthesis implantation
      and inhospital antithrombotic treatment were analyzed. Statistical analysis
      consisted of c2, Fisher's exact, Wilcoxon tests and logistic regression analysis.
      RESULTS: Serious bleedings occurred in 35 (62.5%) patients. There was no
      significant correlation with HASBLED score. History of anemia was a significant
      predictor of bleeding in GUSTO (p = 0.0013) and TIMI (p = 0.048) scales. No
      bleedings in patients receiving vitamin K antagonists (VKA) pre- and VKA plus
      clopidogrel post intervention were observed. Patients with bleedings according to
      the GUSTO scale more often required blood tranfusion than in TIMI scale (p =
      0.03). CONCLUSIONS: History of anemia is the strongest predictor of serious
      bleedings. VKA before and VKA with clopidogrel after TAVI are safer than dual
      antiplatelet or triple therapy. The TIMI and GUSTO scales can adequately classify
      bleeding after TAVI, however the GUSTO better predicts transfusions.

PMID- 23558870
TI  - Aspirin desensitization in patients undergoing percutaneous coronary
      intervention: a survey of current practice.
AB  - BACKGROUND: Aspirin remains the mainstay of anti-platelet therapy in cardiac
      patients. However, if a patient is allergic to aspirin and dual anti-platelet
      therapy is indicated - such as with percutaneous coronary intervention (PCI),
      then there is no clear guidance. One possibility is aspirin desensitization. A
      variety of protocols exist for the rapid desensitization of patients with aspirin
      allergy. The aim of this survey was to assess current knowledge and practice
      regarding aspirin desensitization in the UK. METHODS AND RESULTS: We conducted a
      UK wide survey of all UK 116 PCI centers and obtained complete responses from 40
      (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised
      patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them
      from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization.
      Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25
      (64.1%) units had a clinical strategy for dealing with aspirin allergy; the
      majority (72%) giving higher doses of thienopyridine class drugs. CONCLUSIONS: In
      the UK, there appears to be no consistent approach to patients with aspirin
      allergy. Patients undergoing PCI benefit from dual anti-platelet therapy
      (including aspirin), and aspirin desensitization in those with known allergy may
      facilitate this. Sustained effort should be placed on encouraging UK centers to
      use desensitization as a treatment modality prior to PCI rather than avoiding
      aspirin altogether.

PMID- 23558871
TI  - Comparison of aspirin plus heparin with heparin alone on asymptomatic
      perioperative deep vein thrombosis in candidates for elective off-pump coronary
      artery bypass graft: a randomized clinical trial.
AB  - BACKGROUND: Symptomatic or asymptomatic deep vein thrombosis (DVT) is a common
      complication following coronary artery bypass graft (CABG), in which less than 1%
      of these patients suffer from clinically evident pulmonary embolism (PE). DVT and
      PE can increase other morbidities of coronary revascularization from short to
      long period, but no clear consensus still exists regarding proper
      thromboprophylaxis strategy in the literatures. This study was designed to
      compare the anti-platelet prophylaxis of aspirin plus heparin with heparin alone
      on asymptomatic perioperative DVT in patients that are candidates for elective
      off-pump CABG. METHODS: One hundred and twenty patients, who are candidates for
      elective off-pump CABG, were randomly assigned to two groups: the aspirin plus
      heparin group (Group 1, n = 60) that received 80 mg daily aspirin orally and 5000
      U unfractionated heparin per 8 h subcutaneously from admission to discharge time,
      and the heparin group (group 2, n = 60) that received same dose of heparin alone.
      All patients underwent right and left leg venous ultrasound examination during
      hospitalization, after which post-operative off-pump CABG complications such as
      deep vein thrombosis, bleeding and pulmonary embolism were evaluated in this
      study cases. RESULTS: The mean age of the patients was 62.10 +/- 10.71 years with
      a male to female ratio of 2.24. Asymptomatic DVT occurred in 12 (10%) patients
      who underwent elective off-pump CABG. DVT was found more in Group 2 (16.6%) as
      compared to Group 1 (3.3%) with statistical significant difference (p = 0.015).
      Bleeding was detected in 5 (4.1%) cases in the patients sampled in this study (p
      = 0.34), 4 cases of which are from Group 1 and 1 case from Group 2. However, PE
      was shown in none of this study cases. CONCLUSIONS: The incidence of DVT
      decreased more with aspirin plus heparin as compared to heparin alone in patients
      who underwent elective off-pump CABG. As regards the results obtained in this
      study, more studies need to be conducted to establish this strategy for
      prophylaxis of DVT in CABG.

PMID- 23558872
TI  - Serum biomarkers and clinical outcomes in heart failure patients treated de novo
      with carvedilol.
AB  - BACKGROUND: The role of inflammatory and hemodynamic stress biomarkers in heart
      failure (HF) patients treated de novo with beta-blockers has been poorly studied.
      METHODS: A total of 86 patients (age 56 +/- 9 years, 81 men) with left
      ventricular ejection fraction (LVEF) < 40% and previously not treated with beta
      blockers were initiated on carvedilol. At baseline and 12 months later we
      performed echocardiography, cardiopulmonary exercise testing, and determined
      serum levels of B-type natriuretic peptide (BNP), endothelin-1 (ET-1), C-reactive
      protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNF -a). Patients
      were followed up over a total period of 9 +/- 3 years from baseline. RESULTS:
      Increased baseline CRP and its on-treatment decrease were associated with
      improvement of LVEF (est. coefficient per one SD: 1.6; 95% CI: -0.05,3.28; p =
      0.056, and -1.80; -3.43, -0.18; p = 0.030, respectively) and diminishing of LV
      end-systolic volume index [mL/m2] (-6.83; -11.32; -2.34; p = 0.003, and 5.85;
      1.23; -10.46; p = 0.014, respectively). Higher baseline ET-1 and on-treatment
      increase in TNF-a predicted frequent admissions (> 1) for cardiac complications
      (odds ratio per one SD: 1.98; 95% CI: 1.09-3.59; p = 0.025, and 2.07, 1.12-3.84,
      p = 0.021, respectively) whereas higher baseline BNP was associated with
      increased mortality (hazard ratio per one SD: 2.09, 95% CI: 1.26-3.45; p =
      0.004). CONCLUSIONS: Serum biomarkers may have different roles in prediction of
      clinical outcomes among HF patients treated de novo with carvedilol.

PMID- 23558874
TI  - Broken leads with proximal endings in the cardiovascular system: serious
      consequences and extraction difficulties.
AB  - BACKGROUND: Retrospective analysis of effectiveness, technical problems, and
      complications of transvenous extraction of leads with the free endings migrated
      to the cardiovascular system (CVS). METHODS: A 5-year-old database of transvenous
      lead extraction (TLE) procedures comprising 906 patients with 1563 leads being
      removed was analyzed. TLE procedures of leads migrated in the CVS were compared
      with TLE procedures of leads with their proximal ends accessible in the
      pacemaker/implantable cardioverter-defibrillator (PM/ICD) pocket. RESULTS: In our
      material, the phenomenon of leads migration occurred in 5% of patients referred
      for TLE and affected most frequently unipolar and atrial leads. The presence of
      migrating leads was associated with local venous occlusion in 64% of patients.
      Removal of migrating leads required other techniques than extraction of leads
      with their proximal ends accessible in the PM/ICD pocket. More than 95% of
      migrating leads were extracted transvenously, but procedures were significantly
      longer. The presence of other leads made extraction of migrated leads even more
      complicated. Effectiveness and complication rates for removal of migrated leads
      and leads accessible in the PM/ICD pocket were similar. CONCLUSIONS: We postulate
      that every lead migrating in the CVS should be considered for TLE. However, this
      extraction is technically more difficult and challenging than extraction of leads
      accessible in the PM/ICD pocket.

PMID- 23558873
TI  - Assessment of the cardiac safety and pharmacokinetics of a short course, twice
      daily dose of orally-administered mifepristone in healthy male subjects.
AB  - BACKGROUND: Mifepristone is approved to control hyperglycemia in adults with
      endogenous Cushing's syndrome and is described as a mildly QTc prolonging drug,
      based on a TQT study. The aim of the present study was to assess the effect of
      mifepristone on the QTc interval at plasma mifepristone concentrations exceeding
      those observed in the TQT study. METHODS: Twenty healthy, male volunteers were
      given three doses of 1200 mg mifepristone every 12 h with a high-fat meal in a
      randomized, placebo-controlled 2-period crossover study. Holter ECG recordings
      were made on Day 1 and 2. RESULTS: Eighteen subjects completed the study. Mean
      peak plasma mifepristone concentrations were 4.01 MUg/mL (CV: 31%) on the fi rst
      dose and 5.77 MUg/mL (CV: 29%) on the third dose. Mifepristone did not have a
      meaningful QTc effect. The placebo-corrected, change-from- -baseline QTcF
      (DeltaDeltaQTcF) was between -1.6 and 0.7 ms on the fi rst dose (upper bound of
      90% CI 3.8 ms) and the largest DeltaDeltaQTcF on the third dose was 4.9 ms (upper
      bound of 90% CI: 8.4 ms). Concentration effect modeling showed a slightly
      negative slope of -0.01 ms/ng/mL. CONCLUSIONS: Mifepristone did not cause a
      clinically meaningful QTc prolongation in healthy volunteers at plasma concent
      rations of mifepristone and its main metabolites that clearly exceeded those seen
      in a previous TQT study.

PMID- 23558875
TI  - Association of plasma concentrations of salicylic acid and high on ASA platelet
      reactivity in type 2 diabetes patients.
AB  - BACKGROUND: The objective of this study was to investigate the association
      between plasma concentrations of salicylic acid (SA) and other minor
      acetylsalicylic acid (ASA) metabolites and high on ASA platelet reactivity
      assessed with different methods in type 2 diabetic patients (T2DM). METHODS:
      Study cohort consisted of 293 T2DM patients on chronic ASA therapy. Platelet
      function inhibition was analyzed using measurements of serum thromboxane B2 (S
      TxB2), VerifyNow Aspirin and Platelet Function Analyzer (PFA)-100 assays. The
      concentration of ASA metabolites in plasma was measured with a high-performance
      liquid chromatography (HPLC). RESULTS: In logistic regression analysis both ASA
      dose/kg of body weight and plasma SA concentration were found to be predictive of
      S-TxB2 concentrations above 0.72 ng/mL cut-off point (OR 16.9, 95% CI 2.29-125.8,
      p = 0.006 and OR 5.34, 95% CI 2.67-10.68, p < 0.001, respectively). When using
      the VerifyNow Aspirin Assay, the concentrations of SA were significantly lower (p
      = 0.007) in the group with high on ASA platelet reactivity when compared with the
      group with normal on ASA platelet reactivity. In logistic regression analysis
      plasma SA concentration was found to be predictive of VerifyNow Aspirin Reaction
      Units (ARU) >= 550 (OR 3.86, 95% CI 1.86-8.00, p < 0.001). CONCLUSIONS: Our study
      suggests that disturbances of pharmacokinetic mechanisms might contribute to
      lower plasma SA levels, and subsequently incomplete inhibition of thromboxane A2
      synthesis as measured with S-TxB2 concentrations and increased platelet
      reactivity measured with VerifyNow in T2DM patients.

PMID- 23558876
TI  - Exercise capacity in early and late adult heart transplant recipients.
AB  - BACKGROUND: The aim of this study was to compare peak oxygen consumption (VO(2)),
      heart rate (HR) reserve and HR recovery in early and late heart transplant
      recipients. Moreover, we also aimed to correlate peak VO(2) and HR reserve.
      METHODS: Fivteen heart transplant recipients (8 early and 7 late), 8 +/- 3 and
      161 +/- 58 months after transplantation, respectively, performed a
      cardiopulmonary exercise test. RESULTS: Early heart transplant recipients showed
      lower HR reserve compared to late heart transplant recipients, 39 +/- 15 vs. 58
      +/- 19 bpm (p = 0.049), respectively. Peak VO(2) (23.4 +/- 4 vs. 21.8 +/- 5
      mL/kg/min, p = 0.56), VO(2) respiratory compensation point (18.7 +/- 2 vs. 18.5
      +/- 4 mL/ /kg/min, p = 0.48) and time of exercise testing (14 +/- 3 vs. 13 +/- 3
      min, p = 0.95) %age- -predicted peakVO(2) (65 +/- 12 vs. 70 +/- 10%, p = 0.24)
      were not different between the groups. Moreover, peak VO2 and %age-predicted
      peakVO(2) correlated with HR reserve only in early heart transplant recipients (r
      = 0.89, p = 0.003 and r = 0.71, p = 0.04, respectively). Early heart transplant
      recipients increased HR (2.5 +/- 2.0% at fi rst minute and 0.7 +/- 2.3% at the
      second minute), while late recipients decreased HR (-6.0 +/- 4.7 at fi rst minute
      and -15.5 +/- 2.4 at the second minute) at the recovery period of cardiopulmonary
      exercise test. CONCLUSIONS: Exercise capacity did not show difference between
      early and late heart transplant recipients. HR reserve was higher in late
      compared to early recipients. HR reserve only correlated with peak VO(2) in early
      recipients. Moreover, only late heart transplant recipients showed decrease in HR
      during the recovery period of cardiopulmonary exercise test.

PMID- 23558877
TI  - Prediction of right ventricular dysfunction from radiographic estimates of right
      descending pulmonary artery in hemodynamically stable pulmonary embolism
      patients.
AB  - BACKGROUND: The evaluation of right ventricular (RV) dysfunction by
      echocardiography is one of the most important established determinants of the
      prognosis of acute pulmonary embolism. The aim of the study was to investigate
      possible association between diameter of right descending pulmonary artery on
      chest X-rays and RV dysfunction by echocardiography in hemodynamically stable
      pulmonary embolism patients. METHODS: Eighty-nine patients with the diagnosis of
      hemodynamically stable pulmonary embolism were included. RESULTS: The frequency
      of RV dysfunction was significantly higher in patients with an enlarged right
      descending pulmonary artery on chest X-rays (p = 0.001). There was a significant
      positive correlation between the diameter of the right descending pulmonary
      artery on postero-anterior chest X-rays and the diameter of the RV (r = 0.469; p
      = 0.002). Diameter of right descending pulmonary artery on chest X-rays was also
      found as a significant predictor of RV dysfunction besides the troponin-T levels
      and systolic pulmonary arterial pressure (p < 0.05). CONCLUSIONS: Diameter of
      right descending pulmonary artery on chest X-rays may provide information about
      the risk for pulmonary embolism patients and may be used as a prognostic
      radiological parameter for the appropriate management of acute pulmonary
      embolism.

PMID- 23558878
TI  - Acute myocardial infarction due to left main coronary artery disease: a large
      multicenter national registry.
AB  - BACKGROUND: Optimal management of patients with acute myocardial infarction (MI)
      due to critical stenosis of an unprotected left main coronary artery (ULMCA) is
      not established. However, data from observational studies and registries
      encourage to perform percutaneous coronary intervention (PCI) in high risk
      patients. We investigated gender-related discrepancies, clinical course and
      prognosis in patients with acute MI and ULMCA as an infarct-related artery.
      METHODS: A total of 643 consecutive patients (184 [28.6%] females and 459 [71.4%]
      males) with acute MI due to critical ULMCA stenosis were selected from the
      population of 121,526 patients hospitalized due to acute coronary syndromes
      between 2003 and 2006. The primary endpoints were in-hospital, 30-day, 6-month
      and 12-month mortality. RESULTS: Women were older than men with significantly
      higher proportion of women older than 65 and with unfavorable risk profile. The
      management in men and women was similar. There was no significant gender-related
      differences in mortality in all follow-up periods. In multivariate analysis
      cardiogenic shock, pulmonary edema, ST elevation myocardial infarction (STEMI)
      and advanced age significantly increased mortality, whereas successful PCI
      decreased mortality. CONCLUSIONS: No significant differences in clinical course,
      treatment and prognosis between men and women were noted. Mortality remained very
      high in both genders. The most unfavorable prognostic factors were cardiogenic
      shock, pulmonary edema, STEMI and advanced age. Percutaneous coronary angioplasty
      is feasible and offers high success rate in this subset of patients.

PMID- 23558879
TI  - Protective effects of fasudil hydrochloride post-conditioning on acute myocardial
      ischemia/reperfusion injury in rats.
AB  - BACKGROUND: In recent years, the alleviation of acute myocardial ischemia and
      reperfusion injury (MI/RI) during myocardial reperfusion has presented a
      significant clinical challenge. This study was performed to investigate the
      effects of fasudil hydrochloride (FH) postconditioning on MI/RI and the
      underlying mechanism. METHODS: Seventy-two rats were randomly divided into four
      groups: a Sham group, an ischemia/reperfusion (I/R) group, a fasudil
      hydrochloride (FH) group, and a fasudil hydrochloride+PI3K inhibitor (FH+I)
      group. Myocardial infarct size, cell apoptotic index (AI), and myocardial tissue
      expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1), Bcl
      2, Bcl-2 associated X protein (Bax), caspase-3, Akt and phosphorylated Akt (P
      Akt) were detected. RESULTS: All these parameters, except Akt expression, were
      higher in the I/R group than in the Sham group (p < 0.05). Compared to the I/R
      group, myocardial infarct size, AI, Bax and caspase-3 expression were
      significantly reduced in the FH group (p < 0.05), while Bcl-2 expression was
      increased (p < 0.05). However, the myocardial infarct size and AI of the FH+I
      group were similar to those of the I/R group (p > 0.05). Compared to the FH
      group, Bcl-2 expression was reduced in the FH+I group, while Bax and caspase-3
      expression was increased (p < 0.05). Furthermore, P-Akt expression in the FH
      group was significantly higher than that of the I/R group (p < 0.05).
      CONCLUSIONS: FH post-conditioning alleviated MI/RI, with narrowing of the infarct
      size and decreased apoptosis of ischemic cardiocytes. The mechanism was
      associated with activation of the PI3K-Akt signaling pathway.

PMID- 23558880
TI  - Arrhythmogenic effect of flecainide toxicity.
AB  - Flecainide is a class 1C antiarrhythmic drug especially used for the management
      of supraventricular arrhythmia. In overdose cases, flecainide can induce life
      treating ventricular arrhythmias and cardiogenic shock. We report the case of a
      72-year-old woman admitted to our intensive care unit for a regular monomorphic
      wide complex tachycardia (QRS duration 240 ms, right bundle branch block and
      superior axis morphology) without apparent P waves. Clinical examination showed
      slight left congestive heart failure signs without cardiogenic shock. An
      intravenous bolus of 10 mg adenosine 5'-triphosphate (ATP) was ineffective to
      stop the tachycardia. The diagnosis of ventricular tachycardia induced by
      flecainide overdose was considered. 500 mL of intravenous 840/00 sodium
      bicarbonate was administrated. The patient's QRS narrowed immediately and 12-lead
      ECG showed sinus rhythm. Blood samples confirmed the flecainide overdose and the
      clinical status progressively improved.

PMID- 23558881
TI  - Complete right bundle branch block of unique behavior: what is the mechanism?

PMID- 23558882
TI  - Red cell distribution width: a novel inflammatory marker in clinical practice.

PMID- 23558883
TI  - Author's response.

PMID- 23558884
TI  - Further studies should evaluate multiple predispositions in heart failure
      prognosis.

PMID- 23558885
TI  - Author's response.

PMID- 23558886
TI  - Evaluation of right ventricular functions in patients with acute pulmonary
      embolism.

PMID- 23558887
TI  - Author's response.

PMID- 23558888
TI  - Macrophages: bloody regulators.

PMID- 23558890
TI  - Treadmill endurance during 2-year treatment with tiotropium in patients with
      COPD: a randomized trial.
AB  - BACKGROUND: Disease progression in COPD is associated with a decline in exercise
      performance over time. We assessed whether tiotropium might mitigate this by
      determining its effect on treadmill endurance time (ET) over 2 years. METHODS:
      This was a randomized, double-blind, placebo-controlled trial of tiotropium, 18
      MUg daily, in patients with COPD (FEV1/FVC < 70%; postbronchodilator FEV1 < 65%).
      The primary end point was ET at 90% of baseline maximum work rate at 96 weeks.
      Secondary end points were ET at other visits, ET by smoking status, spirometry,
      and St. George's Respiratory Questionnaire (SGRQ). RESULTS: A total of 519
      patients were randomized (tiotropium 260, placebo 259). Mean age was 65 years,
      77% were men, 34% were continuing smokers, and mean FEV1 was 1.25 L (44%
      predicted). Significantly more patients discontinued placebo (hazard ratio [95%
      CI], 0.61 [0.44-0.83]). Baseline ET was 301 s (improvement tiotropium/placebo was
      13% overall; P = .009; 18% at 48 weeks, P = .004; 13% at 96 weeks, P = .106). In
      patients with baseline ET between 2 and 10 min (n = 404), improvement at 96 weeks
      was 19% (P = .04). Current smokers had higher ET with tiotropium vs placebo (P =
      .018). FEV1/FVC improved with tiotropium (P < .01). SGRQ total score at 96 weeks
      improved with tiotropium vs placebo by 4.03 units (P = .007). CONCLUSIONS:
      Treadmill ET was numerically greater over 2 years with tiotropium vs placebo.
      However, the 96-week difference was not statistically significant. Spirometry and
      health status also improved with tiotropium over 2 years, attesting to the
      benefits of long-acting bronchodilator therapy. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00525512; URL: www.clinicaltrials.gov.

PMID- 23558889
TI  - Protective and pathological roles of mast cells and basophils.
AB  - Mast cells and basophils are potent effector cells of the innate immune system,
      and they have both beneficial and detrimental functions for the host. They are
      mainly implicated in pro-inflammatory responses to allergens but can also
      contribute to protection against pathogens. Although both cell types were
      identified more than 130 years ago by Paul Ehrlich, their in vivo functions
      remain poorly understood. The precursor cell populations that give rise to mast
      cells and basophils have recently been characterized and isolated. Furthermore,
      new genetically modified mouse strains have been developed, which enable more
      specific targeting of mast cells and basophils. Such advances offer new
      opportunities to uncover the true in vivo activities of these cells and to
      revisit their previously proposed effector functions.

PMID- 23558891
TI  - Neoadjuvant FOLFIRI+bevacizumab in patients with resectable liver metastases from
      colorectal cancer: a phase 2 trial.
AB  - BACKGROUND: Preoperative treatment of resectable liver metastases from colorectal
      cancer (CRC) is a matter of debate. The aim of this study was to assess the
      feasibility and activity of bevacizumab plus FOLFIRI in this setting. METHODS:
      Patients aged 18-75 years, PS 0-1, with resectable liver-confined metastases from
      CRC were eligible. They received bevacizumab 5 mg kg(-1) followed by irinotecan
      180 mg m(-)(2), leucovorin 200 mg m(-)(2), 5-fluorouracil 400 mg m(-)(2) bolus
      and 5-fluorouracil 2400 mg m(-)(2) 46-h infusion, biweekly, for 7 cycles.
      Bevacizumab was stopped at cycle 6. A single-stage, single-arm phase 2 study
      design was applied with 1-year progression-free rate as the primary end point,
      and 39 patients required. RESULTS: From October 2007 to December 2009, 39
      patients were enrolled in a single institution. Objective response rate was 66.7%
      (95% exact CI: 49.8-80.9). Of these, 37 patients (94.9%) underwent surgery, with
      a R0 rate of 84.6%. Five patients had a pathological complete remission (14%).
      Out of 37 patients, 16 (43.2%) had at least one surgical complication (most
      frequently biloma). At 1 year of follow-up, 24 patients were alive and free from
      disease progression (61.6%, 95% CI: 44.6-76.6). Median PFS and OS were 14 (95%
      CI: 11-24) and 38 (95% CI: 28-NA) months, respectively. CONCLUSION: Preoperative
      treatment of patients with resectable liver metastases from CRC with bevacizumab
      plus FOLFIRI is feasible, but further studies are needed to define its clinical
      relevance.

PMID- 23558892
TI  - New perspectives on molecular targeted therapy in ovarian clear cell carcinoma.
AB  - Ovarian clear cell carcinomas (OCCCs) account for about 5-13% of all epithelial
      ovarian carcinomas in Western populations. It is characterised by resistance to
      conventional platinum-based chemotherapy, and new therapeutic strategies are
      urgently required. This article will focus on how recent discoveries have
      enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new
      therapeutic opportunities. These include mutations in ARID1A, which provides a
      link to endometriosis, upregulation of the phosphatidylinositol 3-kinase/AKT
      pathway, particularly through mutations of PIK3CA and inactivation of PTEN, and
      increased activity of pathways involved in angiogenesis. Targeting HER2,
      apoptotic escape mechanisms and mismatch repair defects offer additional
      opportunities for treating this enigmatic tumour subtype.

PMID- 23558893
TI  - Mutation analysis of the EGFR gene and downstream signalling pathway in
      histologic samples of malignant pleural mesothelioma.
AB  - BACKGROUND: As epidermal growth factor receptor (EGFR) is involved in the
      pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may
      be effective in treating MPM patients. Mutations of the EGFR gene or its
      downstream effectors may cause constitutive activation leading to cell
      proliferation, and the inhibition of apoptosis and metastases. Consequently,
      molecular profiling is essential for select patients with MPM who may respond to
      anti-EGFR therapies. METHODS: After manual macrodissection, genomic DNA was
      extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8
      sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means
      of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene
      mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct
      sequencing. RESULTS: Gene mutations were identified in nine cases (12%): five
      KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected.
      There was no difference in disease-specific survival between the patients with or
      without gene mutations (P=0.552). CONCLUSIONS: Mutations in EGFR downstream
      pathways are not rare in MPM. Although none of those found in this study seemed
      to be prognostically significant, they may support a more specific selection of
      patients for future trials.

PMID- 23558894
TI  - DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and
      BRCA2 ovarian carcinomas.
AB  - BACKGROUND: Few studies have attempted to characterise genomic changes occurring
      in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have
      been obtained. Given the relevance of DNA copy number alterations in ovarian
      oncogenesis and growing clinical implications of the BRCA-gene status, we aimed
      to characterise the genomic profiles of hereditary and sporadic ovarian tumours.
      METHODS: High-resolution array Comparative Genomic Hybridisation profiling of 53
      familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in
      combination with supervised and unsupervised analysis was used to define common
      and/or specific copy number features. RESULTS: Unsupervised hierarchical
      clustering did not stratify tumours according to their familial or sporadic
      condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning
      genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA
      mutations, and several candidate subtype-specific events were defined. Despite
      similarities, greater contribution of losses was revealed to be a hallmark of
      BRCA1 and BRCA2 tumours. CONCLUSION: Somatic alterations occurring in the
      development of familial EOCs do not differ substantially from the ones occurring
      in sporadic carcinomas. However, some specific features like extensive genomic
      loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify
      BRCA-related patients likely to respond to PARP inhibitors.

PMID- 23558895
TI  - LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker
      and tumour suppressor.
AB  - In baseball parlance, a triple threat is a person who can run, hit and throw with
      aplomb. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a cell
      surface protein that antagonises ERBB receptor signalling by downregulating
      receptor levels. Over 10 years ago, Hedman et al postulated that LRIG1 might be a
      tumour suppressor. Recently, Powell et al provided in vivo evidence
      substantiating that claim by demonstrating that Lrig1 loss in mice leads to
      spontaneously arising, highly penetrant intestinal adenomas. Interestingly, Lrig1
      also marks stem cells in the gut, suggesting a potential role for Lrig1 in
      maintaining intestinal epithelial homeostasis. In this review, we will discuss
      the ability of LRIG1 to act as a triple threat: pan-ERBB negative regulator,
      intestinal stem cell marker and tumour suppressor. We will summarise studies of
      LRIG1 expression in human cancers and discuss possible related roles for LRIG2
      and LRIG3.

PMID- 23558896
TI  - Identification of serum microRNA profiles in colon cancer.
AB  - BACKGROUND: microRNAs (miRNAs) exist in blood in an apparently stable form. We
      have explored whether serum miRNAs can be used as non-invasive early biomarkers
      of colon cancer. METHODS: Serum samples from 30 patients with colon cancer stage
      IV and 10 healthy controls were examined for the expression of 375 cancer
      relevant miRNAs. Based on the miRNA profile in this study, 34 selected miRNAs
      were measured in serum from 40 patients with stage I-II colon cancer and from 10
      additional controls. RESULTS: Twenty miRNAs were differentially expressed in
      serum from stage IV patients compared with controls (P<0.01). Unsupervised
      clustering revealed four subgroups; one corresponding mostly to the control group
      and the three others to the patient groups. Of the 34 miRNAs measured in the
      follow-up study of stage I-II patients, 21 showed concordant expression between
      stage IV and stage I-II patient. Based on the profiles of these 21 miRNAs, a
      supervised linear regression analysis (Partial Least Squares Regression) was
      performed. Using this model we correctly assigned stage I-II colon cancer
      patients based on miRNA profiles of stage IV patients. CONCLUSION: Serum miRNA
      expression profiling may be utilised in early detection of colon cancer.

PMID- 23558897
TI  - Elevated preoperative neutrophil/lymphocyte ratio is associated with poor
      prognosis in soft-tissue sarcoma patients.
AB  - BACKGROUND: Recent data indicate that tumour microenvironment, which is
      influenced by inflammatory cells, has a crucial role in cancer progression and
      clinical outcome of patients. In the present study, we investigated the
      prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to
      tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS)
      patients who underwent curative surgical resection. METHODS: In all, 260 STS
      patients were included in this retrospective study. Kaplan-Meier curves and
      multivariate Cox proportional models were calculated for TTR and OS. RESULTS: In
      univariate analysis, elevated N/L ratio was significantly associated with
      decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30-4.14;
      P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI,
      1.05-3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9
      months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months.
      Regarding OS, elevated N/L ratio was also significantly associated with decreased
      survival in univariate analysis (HR, 2.90; 95%CI, 1.82-4.61; P=0.001) and
      remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14-3.12;
      P=0.014). CONCLUSION: In conclusion, our findings suggest that an elevated
      preoperative N/L ratio predicts poor clinical outcome in STS patients and may
      serve as a cost-effective and broadly available independent prognostic biomarker.

PMID- 23558898
TI  - Tumour-suppressive microRNA-874 contributes to cell proliferation through
      targeting of histone deacetylase 1 in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Our recent studies of microRNA (miRNA) expression signature
      demonstrated that microRNA-874 (miR-874) was significantly downregulated in
      maxillary sinus squamous cell carcinoma (MSSCC), and a putative tumour
      suppressive miRNA in human cancers. Our aim of this study was to investigate the
      functional significance of miR-874 in cancer cells and to identify novel miR-874
      mediated cancer pathways and responsible genes in head and neck squamous cell
      carcinoma (HNSCC). METHODS: Gain-of-function studies using mature miR-874 were
      performed to investigate cell proliferation and cell cycle distribution in HNSCC
      cell lines (SAS and FaDu). To identify miR-874-mediated molecular pathways and
      targets, we utilised gene expression analysis and in silico database analysis.
      Loss-of-function assays were performed to investigate the functional significance
      of miR-874 target genes. RESULTS: Expression levels of miR-874 were significantly
      downregulated in HNSCC tissues (including oral, pharyngeal and laryngeal SCCs)
      compared with normal counterpart epithelia. Restoration of miR-874 in SAS and
      FaDu cell lines revealed significant inhibition of cell proliferation and
      induction of G2/M arrest and cell apoptosis. Our expression data and in silico
      analysis demonstrated that miR-874 modulated the cell cycle pathway. Moreover,
      histone deacetylase 1 (HDAC1) was a candidate target of miR-874 regulation.
      Luciferase reporter assays showed that miR-874 directly regulated HDAC1.
      Silencing of the HDAC1 gene significantly inhibited cell proliferation and
      induced G2/M arrest and cell apoptosis in SAS cells. CONCLUSIONS: Downregulation
      of miR-874 was a frequent event in HNSCC. miR-874 acted as a tumour suppressor
      and directly targeted HDAC1. Recognition of tumour-suppressive miRNA-mediated
      cancer pathways provides new insights into the potential mechanisms of HNSCC
      oncogenesis and suggests novel therapeutic strategies for the disease.

PMID- 23558899
TI  - Childhood leukaemia close to high-voltage power lines--the Geocap study, 2002
      2007.
AB  - BACKGROUND: High-voltage overhead power lines (HVOLs) are a source of extremely
      low-frequency magnetic fields (ELF-MFs), which are classified as possible risk
      factors for childhood acute leukaemia (AL). The study was carried out to test the
      hypothesis of an increased AL incidence in children living close to HVOL of 225
      400 kV (VHV-HVOL) and 63-150 kV (HV-HVOL). METHODS: The nationwide Geocap study
      included all the 2779 cases of childhood AL diagnosed in France over 2002-2007
      and 30 000 contemporaneous population controls. The addresses at the time of
      inclusion were geocoded and precisely located around the whole HVOL network.
      RESULTS: Increased odds ratios (ORs) were observed for AL occurrence and living
      within 50 m of a VHV-HVOL (OR=1.7 (0.9-3.6)). In contrast, there was no
      association with living beyond that distance from a VHV-HVOL or within 50 m of a
      HV-HVOL. CONCLUSION: The present study, free from any participation bias,
      supports the previous international findings of an increase in AL incidence close
      to VHV-HVOL. In order to investigate for a potential role of ELF-MF in the
      results, ELF-MF at the residences close to HVOL are to be estimated, using models
      based on the annual current loads and local characteristics of the lines.

PMID- 23558900
TI  - Triple-negative breast cancer: BRCAness and concordance of clinical features with
      BRCA1-mutation carriers.
AB  - BACKGROUND: BRCAness is defined as shared tumour characteristics between sporadic
      and BRCA-mutated cancers. However, how to exactly measure BRCAness and its
      frequency in breast cancer is not known. Assays to establish BRCAness would be
      extremely valuable for the clinical management of these tumours. We assessed
      BRCAness characteristics frequencies in a large cohort of triple-negative breast
      cancers (TNBCs). METHODS: As a measure of BRCAness, we determined a specific
      BRCA1-like pattern by array Comparative Genomic Hybridisation (aCGH), and BRCA1
      promoter methylation in 377 TNBCs, obtained from 3 different patient cohorts.
      Clinicopathological data were available for all tumours, BRCA1-germline mutation
      status and chemotherapy response data were available for a subset. RESULTS: Of
      the tumours, 66-69% had a BRCA1-like aCGH profile and 27-37% showed BRCA1
      promoter methylation. BRCA1-germline mutations and BRCA1 promoter methylation
      were mutually exclusive events (P=1 * 10(-5)). BRCAness was associated with
      younger age and grade 3 tumours. Chemotherapy response was significantly higher
      in BRCA1-mutated tumours, but not in tumours with BRCAness (63% (12 out of 19) vs
      35% (18 out of 52) pathological complete remission rate, respectively).
      CONCLUSION: The majority of the TNBCs show BRCAness, and those tumours share
      clinicopathological characteristics with BRCA1-mutated tumours. A better
      characterisation of TNBC and the presence of BRCAness could have consequences for
      both hereditary breast cancer screening and the treatment of these tumours.

PMID- 23558901
TI  - An antiapoptotic Bcl-2 family protein index predicts the response of leukaemic
      cells to the pan-Bcl-2 inhibitor S1.
AB  - BACKGROUND: Bcl-2-like members have been found to be inherently overexpressed in
      many types of haematologic malignancies. The small-molecule S1 is a BH3 mimetic
      and a triple inhibitor of Bcl-2, Mcl-1 and Bcl-XL. METHODS: The lethal dose 50
      (LD(50)) values of S1 in five leukaemic cell lines and 41 newly diagnosed
      leukaemia samples were tested. The levels of Bcl-2 family members and
      phosphorylated Bcl-2 were semiquantitatively measured by western blotting. The
      interactions between Bcl-2 family members were tested by co-immunoprecipitation.
      The correlation between the LD(50) and expression levels of Bcl-2 family members,
      alone or in combination, was analysed. RESULTS: S1 exhibited variable sensitivity
      with LD(50) values ranging >2 logs in both established and primary leukaemic
      cells. The ratio of pBcl-2/(Bcl-2+Mcl-1) could predict the S1 response.
      Furthermore, we demonstrated that pBcl-2 antagonised S1 by sequestering the Bak
      and Bim proteins that were released from Mcl-1, andpBcl-2/Bak, pBcl-2/Bax and
      pBcl-2/Bim complexes cannot be disrupted by S1. CONCLUSION: A predictive index
      was obtained for the novel BH3 mimetic S1. The shift of proapoptotic proteins
      from being complexed with Mcl-1 to being complexed with pBcl-2 was revealed for
      the first time, which is the mechanism underlying the index value described
      herein.

PMID- 23558902
TI  - Regulation of some carbohydrate metabolism-related genes, starch and soluble
      sugar contents, photosynthetic activities and yield attributes of two contrasting
      rice genotypes subjected to salt stress.
AB  - Soluble carbohydrates play a key role as osmolytes and significantly contribute
      in salt defence mechanism, especially in halophyte species. The objective of this
      study is to investigate the transcriptional expression of starch-related genes,
      sugar profile and physiological performances of two contrasting rice genotypes,
      Pokkali (salt tolerant) and IR29 (salt sensitive), in response to salt stress.
      Total soluble sugars, glucose and fructose levels in the flag leaf of salt
      stressed Pokkali rice were enhanced relative to soluble starch accumulation in
      plants exposed to EC = 13.25 dS m(-1) (salt stress) for 3 days. In Pokkali, the
      net photosynthetic rate and starch metabolism may play a key role as energy
      resources under salt stress. In contrast, photosynthetic performance, indicated
      by photosynthetic pigment levels and chlorophyll fluorescence parameters, in salt
      stressed IR29 was significantly reduced, leading to delayed starch biosynthesis.
      The reduction in photosynthetic ability and lack of defence mechanisms in IR29
      caused growth inhibition and yield loss. Soluble starch and soluble sugar
      enrichment in Pokkali rice may function alternatively as osmotic adjustment in
      salt defence mechanism and strengthen carbon energy reserves, greater survival
      prospects under salt stress and enhanced productivity.

PMID- 23558903
TI  - An unprecedented 3D POM-Ag architecture with intertwined and homological helical
      structures.
AB  - A new hybrid compound, Na[Ag6(pyttz)2(H2O)][PMo12O40] (pyttz = 3-(pyrid-3-yl)-5
      (1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl), has been hydrothermally synthesized and
      structurally characterized by routine techniques. X-ray diffraction analysis
      reveals that the title compound is constructed by the 2D Ag-pyttz coordination
      polymer and 3D Ag-POM architecture with helix. A fascinating structural feature
      is the assembling fashion of the right- and left-helical chain, namely, the
      helical chains with different orientations are intertwined with each other
      forming intertwined double helical layers along the c-axis, and the identical
      left- or right-handed helical chains are fused together in a hand-by-hand mode
      generating another homological helical layer along the a-axis. As a result, these
      helical layers intersect each other obtaining an unprecedented 3D POM-Ag
      inorganic architecture. Note that the 3D framework with a helix constructed by
      POMs and metal ions has never been observed up to date. Additionally, its
      photocatalytic degradation of RhB was also investigated.

PMID- 23558904
TI  - Correlates of care for young men with Duchenne and Becker muscular dystrophy.
AB  - INTRODUCTION: In progressive conditions, such as Duchenne and Becker muscular
      dystrophy (DBMD), the need for care may outpace care use. We examined correlates
      that contribute to utilization of needed care. METHODS: Structured interviews
      were conducted on use of care among 34 young men with DBMD who were born before
      1982. RESULTS: Disease severity, per capita income, and presence of other
      relatives with DBMD predicted greater use of services. Race/ethnicity,
      acculturation, and level of caregiver education did not significantly predict
      service utilization. CONCLUSIONS: We identified disparities in receipt of
      healthcare and related services in adult men with DBMD that can affect quality of
      life. Despite the high disease severity identified in this population, these men
      utilized only half of the services available to individuals with significant
      progressive conditions. Providers should be aware of low service utilization and
      focus on awareness and assistance to ensure access to available care.

PMID- 23558905
TI  - Escalated daunorubicin dosing as an induction treatment for Philadelphia-negative
      adult acute lymphoblastic leukemia.
AB  - The dose intensity of daunorubicin (DNR) delivered during the induction period
      represented the major prognostic factor for the outcome of adult acute
      lymphoblastic leukemia (ALL). The aim of this study was to determine the survival
      or toxicity of escalated doses of DNR in induction treatment of adult patients
      with acute lymphoblastic leukemia who are at least 15 years of age. For induction
      chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous
      intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV
      push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1
      14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or
      subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69).
      Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died
      before CR was reached. Additionally, 11 patients died from leukemia progression,
      4 had refractory disease, and 3 had follow-up loss. The median follow-up time was
      697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3
      %. The probabilities of disease-free survival and overall survival at 3 years
      were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose,
      and there were no additional specific toxicities. The results show that escalated
      doses of DNR in induction chemotherapy are similar with the standard dose in
      response and toxicities. Our study indicates that a more effective regimen or
      better chemotherapy agents are needed to improve the CR rate and prolong survival
      in Philadelphia-negative adult ALL. 

PMID- 23558906
TI  - Impact of NOD2 polymorphisms on infectious complications following chemotherapy
      in patients with acute myeloid leukaemia.
AB  - We sought to investigate the relationship between polymorphisms of the NOD2 gene
      and infectious complications following intensive induction chemotherapy in
      patients with acute myeloid leukaemia (AML). We hypothesised that single
      nucleotide polymorphisms (SNPs) of the NOD2 gene are associated with a higher
      rate of infections during the phase of severe neutropenia. In 131 AML patients
      receiving induction therapy, the presence of the three most frequent
      polymorphisms of NOD2 (Arg702Trp, Gly908Arg, Leu1007fsinsC) was analysed. SNP
      analyses by means of genomic PCR incorporating fluorescence-labelled probes with
      characteristic melting curves were performed using the LightCycler platform. Our
      data suggest a significantly lower probability of mucositis or enteritis in AML
      patients lacking any of the three evaluated NOD2 polymorphisms. Furthermore,
      bloodstream cultures of AML patients carrying either a missense or a frameshift
      mutation of NOD2 were significantly more frequently tested positive concerning
      Streptococcus spp. In contrast, the presence of NOD2 polymorphisms had no impact
      on such important infectious complications as systemic inflammatory response
      syndrome or sepsis, the rate of central venous catheter infections or the
      incidence of pneumonia including fungal infections. Our data represent one of the
      first reports investigating the impact of polymorphisms of the innate immune
      system on infectious complications in patients with neutropenia following
      chemotherapy. A correlation between NOD2 polymorphisms and infectious events in
      AML patients is demonstrated. 

PMID- 23558907
TI  - Sequential Hodgkin's and non-Hodgkin's lymphoma in non-immunocompromised
      patients.

PMID- 23558908
TI  - Concerns regarding data supporting recent Pneumocystis jirovecii prophylaxis
      guidelines.

PMID- 23558909
TI  - Goal-directed intraoperative fluid therapy guided by stroke volume and its
      variation in high-risk surgical patients: a prospective randomized multicentre
      study.
AB  - Perioperative hemodynamic optimisation improves postoperative outcome for
      patients undergoing high-risk surgery (HRS). In this prospective randomized
      multicentre study we studied the effects of an individualized, goal-directed
      fluid management based on continuous stroke volume variation (SVV) and stroke
      volume (SV) monitoring on postoperative outcomes. 64 patients undergoing HRS were
      randomized either to a control group (CON, n = 32) or a goal-directed group (GDT,
      n = 32). In GDT, SVV and SV were continuously monitored (FloTrac/Vigileo) and
      patients were brought to and maintained on the plateau of the Frank-Starling
      curve (SVV <10 % and SV increase <10 % in response to fluid loading). Organ
      dysfunction was assessed using the SOFA score and resource utilization using the
      TISS score. Patients were followed up to 28 days for postoperative complications.
      Main outcome measures were the number of complications (infectious, cardiac,
      respiratory, renal, hematologic and abdominal post-operative complications),
      maximum SOFA score and cumulative TISS score during ICU stay, duration of
      mechanical ventilation, length of ICU stay, and time until fit for discharge. 12
      patients had to be excluded from final analysis (6 in each group). During
      surgery, GDT received more colloids than CON (1,589 vs. 927 ml, P < 0.05) and SVV
      decreased in GDT (from 9.0 to 8.0 %, P < 0.05) but not in CON. The number of
      postoperative wound infections was lower in GDT (0 vs. 7, P < 0.01). Although not
      statistically significant, the proportion of patients with at least one
      complication (46 vs. 62 %), the number of postoperative complications per patient
      (0.65 vs. 1.40), the maximum sofa score (5.9 vs. 7.2), and the cumulative TISS
      score (69 vs. 83) tended to be lower. This multicentre study shows that fluid
      management based on a SVV and SV optimisation protocol is feasible and decreases
      postoperative wound infections. Our findings also suggest that a goal-directed
      strategy might decrease postoperative organ dysfunction.

PMID- 23558910
TI  - [Specific variability of teicoplanin protein binding in patients receiving
      continuous hemodiafiltration-comparison with hypoalbuminemia patients].
AB  - Variation in protein binding ratio (PBR) of teicoplanin (TEIC) was investigated
      in continuous hemodiafiltration (CHDF) patients. TEIC is classified as a high PBR
      drug (?90%), and it was reported that the PBR of TEIC decreased with an decrease
      in the serum albumin level in hypoalbuminemia patients. However, few reports can
      be found about the variation of PBR of TEIC for CHDF patient. An antibiotic
      activity is directly determined by the level of unbound antibiotics species
      (Cfree) in the target site, namely, an increase in the Cfree enhances the risks
      of TEIC as well as the therapeutic effect against Methicillin-resistant
      Staphylococcus aureus (MRSA). In this study, both the total concentration
      (Ctotal) and Cfree of TEIC were determined and the PBRs were compared between a
      patient with normal albumin level, hypoalbuminemia patients and CHDF patients.
      Similarly to the previous report, the lowering of PBR of TEIC was demonstrated in
      the hypoalbuminemia patients. On the other hand, the CHDF patients showed lower
      value of PBR suggesting some change in the protein binding ability, although
      showed higher values of serum albumin level in comparison with the
      hypoalbuminemia patients. It was not necessary to measure the Cfree value for the
      hypoalbuminemia patient routinely, but the monitoring of Cfree as well as Ctotal
      for the CHDF patients can be important for the proper TEIC use because of the
      potential specialty of PBR.

PMID- 23558911
TI  - Systemic therapy for inoperable and metastatic basal cell cancer.
AB  - Cutaneous basal cell carcinoma (BCC) is the most common human malignancy. The
      majority of cases are cured with local therapies and advanced disease is quite
      rare. However, locally advanced (inoperable) and metastatic basal cell carcinoma
      may occur more often than previously thought. Surgery, and other local therapies,
      is the primary treatment for BCC. However, some resections can be extensive and
      carry significant morbidity or disfigurement. The prognosis for locally advanced
      and metastatic BCC is quite poor, and cytotoxic chemotherapies offer limited
      benefit. Aberrations in the sonic hedgehog (HH) signaling pathway are common in
      BCC. Novel molecular therapies targeted against this pathway, such as vismodegib
      (GDC-0449), have shown dramatic activity in advanced basal cell carcinoma. The
      role of these in nevoid basal cell carcinoma syndrome (Gorlin) syndrome is still
      under investigation. However, systemic therapies are not curative and require
      long-term treatment and should not be used in place of curative procedures.
      Evaluation by experienced physicians and/or by a multidisciplinary tumor board
      for possible curative/definitive surgery with or without radiation is recommended
      before initiation of systemic therapy. Clinical trial enrollment also is
      recommended. Comorbid conditions as well as social circumstances may be factors
      when deciding on an optimal therapy, in particular with oral agents. Patients
      treated with HH pathway inhibitors require regular physician monitoring to assess
      for side effects, benefit, and compliance. Patients of child-bearing potential
      must be strongly counseled regarding the risk of birth defects and need for birth
      control. Primary and secondary resistance to HH pathway inhibitors is only
      beginning to be described.

PMID- 23558913
TI  - Electroencephalography when meditation advances: a case-based time-series
      analysis.
AB  - Increased alpha and theta activities in electroencephalography (EEG) have been
      found during various forms of meditation. However, advanced stage of meditation
      drew less attention to date. We aimed at exploring EEG characteristics during
      advanced meditation. Bilateral absolute alpha and theta EEG powers were recorded
      when a single meditator at rest, exercising breath meditation, and reaching the
      advanced meditative stage in 10 sessions of meditation. Averaged time-series data
      were analyzed using simulation modeling analysis to compare the powers during
      different meditative phases. During breath meditation, significantly higher
      activities compared with baseline were found only in bilateral theta (P = 0.0406,
      0.0158 for left and right sides, respectively), but not in alpha (P = 0.1412,
      0.0978 for left and right sides, respectively) bands. When meditation advanced,
      significantly increased activities were found both in bilateral alpha (P =
      0.0218, 0.0258 for left and right sides, respectively) and theta (P = 0.0308,
      0.0260 for left and right sides, respectively) bands compared against breath
      meditation. When advanced meditation compared against baseline, bilateral alpha
      (P = 0.0001, 0.0001 for left and right sides, respectively) and theta (P =
      0.0001, 0.0001 for left and right sides, respectively) bands revealed
      significantly increased activities. Our findings support that internalized
      attention manifested as theta activity continuingly enhances significantly in
      sequential phases of meditation, while relaxation manifested as alpha activity is
      significant only after the advanced meditative phase is reached.

PMID- 23558914
TI  - Infusion nurses: we're worth it.

PMID- 23558915
TI  - Multiple endocrine neoplasia syndromes.
AB  - Multiple endocrine neoplasia (MEN) is a term used to describe a group of
      hereditary carcinoma syndromes. Patients carrying a characteristic autosomal
      dominant gene aberration exhibit various endocrine carcinomas, as well as other
      anatomical abnormalities. Unfortunately, familial endocrine carcinoma patients
      are too often unrecognized by primary care providers, resulting in delayed
      diagnosis and treatment, with profound consequences related to morbidity and
      mortality. This article will introduce the various MEN syndromes and the infusion
      nurse's role in the care of these individuals and their families.

PMID- 23558916
TI  - Rituximab faster infusion for patients with non-Hodgkin's lymphoma in the United
      States: implications for nursing practice.
AB  - The majority of follicular non-Hodgkin's lymphoma patients in the United States
      receive an initial treatment strategy that includes the infusion of rituximab.
      Data from a phase III multicenter clinical trial led to the 2012 US Food and Drug
      Administration approval of a 90-minute infusion of rituximab (Rituxan) starting
      at Cycle 2 for patients with non-Hodgkin's lymphoma who did not experience a
      Grade 3 or 4 infusion-related adverse event during Cycle 1. A review of
      literature was undertaken to identify existing evidence regarding both the safety
      of rituximab faster infusion and its impact on nursing practice. The aim of this
      article is to stimulate discussion and lead to implementation of evidence-based
      nursing practices to improve the delivery of patient care.

PMID- 23558917
TI  - A prospective postmarket study to evaluate the safety and efficacy of a new
      peripherally inserted central catheter stabilization system.
AB  - An initial postmarket study of the SecurAcath used with 5 Fr peripherally
      inserted central catheters (PICCs) was conducted with 68 adult patients at 3
      different institutions in the United States. PICCs were placed in both
      outpatients and inpatients, with patients in critical care and medical/surgical
      units, home care, and extended care facilities. Sixty-two (91.2%) of the patients
      completed therapy without a securement-related device malfunction or device
      related adverse event associated with the securement system. The device was
      readily accepted by both patients and nursing staff. The SecurAcath represents a
      novel, safe, and effective method for catheter securement.

PMID- 23558918
TI  - Intravenous smart pumps.
AB  - Intravenous (IV) smart pumps provide substantial safety features during infusion.
      However, nurses need to understand the requisite education necessary to fully
      benefit from and improve IV smart pump use and clinical integration. Failure to
      use IV smart pumps places the nurse and patient at increased risk.

PMID- 23558919
TI  - Safe handling of chemotherapeutic agents in the treatment of nonmalignant
      diseases.
AB  - Chemotherapy administration was once limited to inpatient oncology units. Over
      time, outpatient facilities, physicians' private offices, and patients' homes
      have become popular areas to administer chemotherapeutic agents. Chemotherapy has
      been successful in treating malignancies and recently has been proved to be
      effective in nononcology patients as well. The expanded use of these agents has
      created the need to amplify safe handling practices among health care providers.
      Evidence indicates that there is a heightened awareness of safe handling
      practices and the increased availability of the necessary tools. However, health
      care professionals resist protecting themselves. To avoid the potential risks
      associated with working with these agents, it is imperative to appreciate the
      dangers of these hazardous medications, to adhere to the safety mechanisms, and
      to use the available safety resources on a daily basis. Continuous education of
      health care providers is fundamental to ensuring safety and positive outcomes.
      Safe handling procedures can be implemented by adhering to the current standards
      and integrating them into policies and procedure manuals at practicing
      institutions.

PMID- 23558920
TI  - Safe practice: using high-fidelity simulation to teach blood transfusion
      reactions.
AB  - High-fidelity simulation can play an important role in educating novice nurses
      for a challenging health care environment by fostering their confidence levels in
      recognizing high-risk, low-incident events. This paper reports on a quality
      improvement project to increase student nurses' knowledge and skills in caring
      for clients receiving blood transfusions.

PMID- 23558921
TI  - KLF4 promoted odontoblastic differentiation of mouse dental papilla cells via
      regulation of DMP1.
AB  - Odontoblasts, which derive from dental papilla, are a type of terminally
      differentiated matrix-secreting cells. Previous studies have identified various
      transcription factors involved in the differentiation process of odontoblasts. We
      have recently found that Kruppel-like factor 4 (Klf4) was expressed in the
      polarizing and elongating odontoblasts, but the function of Klf4 in the
      differentiation of odontoblasts is still unclear. We hypothesized Klf4 promoted
      the differentiation of odontoblasts by up-regulating some odontoblast-related
      genes. In this study, we found that the expression of Klf4 increased
      significantly during the odontoblastic differentiation of primary mouse dental
      papilla cells and the mouse dental papilla cell line-mDPC6T. Overexpression of
      Klf4 significantly up-regulated odontoblast-related genes, such as Dmp1, Dspp,
      and Alp, and promoted the accumulation of mineral nodules. Knock-down of Klf4
      down-regulated expression of Dmp1, Dspp, and Alp, and inhibited mineral
      deposition. We applied in silico analysis and identified one target gene of Klf4
      Dmp1. Based on further analysis of ChIP data, EMSA and dual luciferase activity
      assays, we confirmed that Klf4 was able to specifically bind to the Dmp1 promoter
      and transactivate its expression. Furthermore, forced expression of Dmp1 in the
      Klf4 knock-down mDPC6T cell line significantly recovered its odontoblastic
      differentiation ability. Our data confirmed our hypothesis that Klf4 promotes the
      differentiation of odontoblasts via the up-regulation of Dmp1.

PMID- 23558922
TI  - Hospital decentralisation in Romania: stakeholders' perspectives in the newsprint
      media.
AB  - In the summer of 2010, Romania undertook a process of hospital decentralisation
      as part of the reform in the healthcare sector. The national newsprint media
      covered the process thoroughly. This paper is a study of how key stakeholders'
      views, attitudes, beliefs and attitudes towards decentralisation are represented
      in print media. 106 articles, published between June and September 2010,
      retrieved from the online databases of six leading national dailies were
      analysed. A mixed methodology was used in the data analysis stage. The
      qualitative data exploration identified five voices belonging to stakeholders
      involved directly or indirectly in the process: the representatives of central
      government, the local authorities (district and local councils, municipal
      mayors), health professionals (managers and physicians in hospitals), the media
      (journalists, analysts) and finally voices from civil society, professional
      associations and advocacy groups. These were the main actors negotiating the
      subjective meanings of the decentralisation process. An imbalance between these
      key actors were observed in the frequency, content and tone of the messages
      delivered in media during the four months. Central government and the local
      authorities were the most active voices, but the respective discourses differed
      significantly. An analysis of the accounts identified three main themes: the
      financial problem (hospitals liabilities and future spending), human resource in
      hospitals (the impact of decentralisation upon it) and the political character of
      the decentralisation.

PMID- 23558923
TI  - Very late stent thrombosis after sirolimus-eluting stent implantation: evaluation
      by intravascular ultrasound and optical coherence tomography.
AB  - A 58-year-old man was admitted to our hospital with acute anterior myocardial
      infarction that occurred 4 years after single sirolimus-eluting stent (SES)
      implantation in the left anterior descending artery. He had been undergoing
      continuous dual antiplatelet therapy. Emergency coronary angiography showed total
      thrombotic occlusion and peri-stent contrast staining at the SES site. The lesion
      was evaluated using intravascular ultrasound (IVUS) and optical coherence
      tomography (OCT) after thrombectomy. Vessel remodeling was detected on IVUS, and
      multiple interstrut hollows and thrombi were observed on OCT. These findings were
      associated with very late stent thrombosis after SES implantation.

PMID- 23558912
TI  - Jasmonates: biosynthesis, perception, signal transduction and action in plant
      stress response, growth and development. An update to the 2007 review in Annals
      of Botany.
AB  - BACKGROUND: Jasmonates are important regulators in plant responses to biotic and
      abiotic stresses as well as in development. Synthesized from lipid-constituents,
      the initially formed jasmonic acid is converted to different metabolites
      including the conjugate with isoleucine. Important new components of jasmonate
      signalling including its receptor were identified, providing deeper insight into
      the role of jasmonate signalling pathways in stress responses and development.
      SCOPE: The present review is an update of the review on jasmonates published in
      this journal in 2007. New data of the last five years are described with emphasis
      on metabolites of jasmonates, on jasmonate perception and signalling, on cross
      talk to other plant hormones and on jasmonate signalling in response to
      herbivores and pathogens, in symbiotic interactions, in flower development, in
      root growth and in light perception. CONCLUSIONS: The last few years have seen
      breakthroughs in the identification of JASMONATE ZIM DOMAIN (JAZ) proteins and
      their interactors such as transcription factors and co-repressors, and the
      crystallization of the jasmonate receptor as well as of the enzyme conjugating
      jasmonate to amino acids. Now, the complex nature of networks of jasmonate
      signalling in stress responses and development including hormone cross-talk can
      be addressed.

PMID- 23558924
TI  - Forearm blood flow response to acute exercise in obese and non-obese males.
AB  - Chronic exercise is thought to improve endothelium-dependent vasodilation;
      however, few studies have evaluated the effects of acute exercise on
      microvascular vasodilatory capacity (MVC). Moreover, no studies have compared MVC
      responses in obese and non-obese individuals following acute exercise. To
      evaluate MVC, utilizing forearm blood flow (FBF) and excess blood flow (EBF)
      before and up to 48 h after a single exercise bout to elicit peak oxygen
      consumption (VO2 peak) in obese and non-obese males. Twelve obese (37.0 +/- 1.1
      kg/m(2)) and 12 non-obese (21.9 +/- 0.3 kg/m(2)) males volunteered to
      participate. FBF measures, before and during reactive hyperemia (RH), were
      obtained prior to (PRE-E), immediately after (POST-E), and at 1 (POST-1), 2 (POST
      2), 24 (POST-24), and 48 (POST-48) hours after exercise. EBF, was calculated as
      the difference between FBF, before and during RH. Blood samples were obtained to
      evaluate the response of interleukin-6 (IL-6) and tumor necrosis factor alpha
      (TNF-alpha), which are potential modifiers of MVC. FBF before and during RH were
      significantly (P < 0.05) increased in both groups POST-E. The EBF magnitude of
      change from PRE-E was significantly (P < 0.05) elevated in non-obese when
      compared with obese males. Although not related to MVC, concentrations of IL-6
      significantly decreased between POST-2 and POST-24 in both groups. An acute bout
      of exercise designed to elicit VO2 peak significantly increased forearm MVC in
      non-obese and obese males, although the magnitude of change in EBF from PRE-E to
      POST-E was greater in non-obese males.

PMID- 23558925
TI  - Blood pressure regulation: every adaptation is an integration?
AB  - This focused review serves to explore relevant issues in regard to blood pressure
      regulation and by doing so, provides the initial stimulus paper for the Thematic
      Review series "Blood Pressure Regulation" to be published in the European Journal
      of Applied Physiology over the coming months. In this introduction, we highlight
      how variable normal blood pressure can be and challenge the reader to take
      another look at some key concepts related to blood pressure regulation. We point
      out that there is frequently an underappreciated balance between peripheral
      vasodilation and systemic blood pressure regulation and ask the question: are
      changes in blood pressure, in effect, reasonable and integrated adaptations to
      the physiological challenge at hand? We conclude with the idea that blood
      pressure regulatory systems are both flexible and redundant; ensuring a wide
      variety of activities associated with life can be accompanied by a perfusion
      pressure that can serve multiple masters. 

PMID- 23558926
TI  - Cell division: different daughters.

PMID- 23558927
TI  - DNA replication: quality and quantity.

PMID- 23558928
TI  - DNA repair: repair with a twist.

PMID- 23558929
TI  - Procedural volume and structure of interventional pulmonary fellowships: a survey
      of fellows and fellowship program directors.
AB  - BACKGROUND: Current interventional pulmonary (IP) procedural guidelines for
      competency are based on expert opinion. There are few objective data to support
      competency metrics for IP procedures. This survey reports procedural volume
      during IP fellowships to help define new standards in training and curriculum
      development. METHODS: A web-based survey was developed to evaluate IP training
      procedural volume. The survey was administered to all US and Canadian IP
      fellowship directors and graduates in training from 2006 to 2011. The survey
      inquired about all diagnostic and therapeutic procedures performed during the
      specialized year of IP training. Questions regarding the training program
      structure were collected and analyzed. RESULTS: There was a 92.5% fellow response
      rate (37 of 40) and 77% fellowship director response rate (10 of 13) from
      programs in existence at the time of the survey. Procedural volume was consistent
      between fellowship directors and graduates (P = .64). Although there was a wide
      range of procedural volume and types of procedures between different programs,
      the procedural mean volumes were all significantly higher than the American
      College of Chest Physicians (ACCP) and American Thoracic Society/European
      Respiratory Society (ATS/ERS) guideline recommendations (P < .005). CONCLUSIONS:
      US and Canadian IP fellowships produce fellows with variable procedural volumes;
      however, these are significantly higher than ACCP and ATS/ERS guidelines for most
      programs and procedures. With a uniform training curriculum being adopted by the
      majority of IP fellowship programs in the United States and Canada, as well as
      data showing improved core knowledge in IP fellows undergoing a dedicated year of
      additional training, further metrics examining the impact of advanced IP training
      on patient outcomes are needed.

PMID- 23558930
TI  - Planar chiral [2.2]paracyclophane-based bis(thiourea) catalyst: application to
      asymmetric Henry reaction.
AB  - A bis(thiourea) organocatalyst with a planar chiral [2.2]paracyclophane backbone
      has been synthesized and applied to the Henry reaction. The obtained high
      reactivity and enantioselectivity from the reaction of aromatic aldehydes with
      nitroalkanes suggested the significant potential of [2.2]paracyclophane to serve
      as the backbone of the organocatalyst.

PMID- 23558931
TI  - Challenges in the research and development of new human vaccines.
AB  - The field of vaccinology was born from the observations by the fathers of
      vaccination, Edward Jenner and Louis Pasteur, that a permanent, positive change
      in the way our bodies respond to life-threatening infectious diseases can be
      obtained by specific challenge with the inactivated infectious agent performed in
      a controlled manner, avoiding the development of clinical disease upon exposure
      to the virulent pathogen. Many of the vaccines still in use today were developed
      on an empirical basis, essentially following the paradigm established by Pasteur,
      "isolate, inactivate, and inject" the disease-causing microorganism, and are
      capable of eliciting uniform, long-term immune memory responses that constitute
      the key to their proven efficacy. However, vaccines for pathogens considered as
      priority targets of public health concern are still lacking. The literature tends
      to focus more often on vaccine research problems associated with specific
      pathogens, but it is increasingly clear that there are common bottlenecks in
      vaccine research, which need to be solved in order to advance the development of
      the field as a whole. As part of a group of articles, the objective of the
      present report is to pinpoint these bottlenecks, exploring the literature for
      common problems and solutions in vaccine research applied to different
      situations. Our goal is to stimulate brainstorming among specialists of different
      fields related to vaccine research and development. Here, we briefly summarize
      the topics we intend to deal with in this discussion.

PMID- 23558932
TI  - Myosin Va is developmentally regulated and expressed in the human cerebellum from
      birth to old age.
AB  - Myosin Va functions as a processive, actin-based motor molecule highly enriched
      in the nervous system, which transports and/or tethers organelles, vesicles, and
      mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli
      disease that is associated with severe neurological deficits and a short life
      span. Despite playing a critical role in development, the expression of myosin Va
      in the central nervous system throughout the human life span has not been
      reported. To address this issue, the cerebellar expression of myosin Va from
      newborns to elderly humans was studied by immunohistochemistry using an affinity
      purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the
      10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular
      cerebellar layers. Cerebellar myosin Va expression did not differ essentially in
      localization or intensity from childhood to old age, except during the postnatal
      developmental period. Structures resembling granules and climbing fibers in
      Purkinje cells were deeply stained. In dentate neurons, long processes were
      deeply stained by anti-myosin Va, as were punctate nuclear structures. During the
      first postnatal year, myosin Va was differentially expressed in the external
      granular layer (EGL). In the EGL, proliferating prospective granule cells were
      not stained by anti-myosin Va antibody. In contrast, premigratory granule cells
      in the EGL stained moderately. Granule cells exhibiting a migratory profile in
      the molecular layer were also moderately stained. In conclusion, neuronal myosin
      Va is developmentally regulated, and appears to be required for cerebellar
      function from early postnatal life to senescence.

PMID- 23558933
TI  - The expression of Egfl7 in human normal tissues and epithelial tumors.
AB  - BACKGROUND AND AIMS: To investigate the expression of Egfl7 in normal adult human
      tissues and human epithelial tumors.? METHODS: RT-PCR and Western blot were
      employed to detect Egfl7 expression in normal adult human tissues and 10 human
      epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast
      cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer,
      malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and
      cytoimmunofluorescence were subsequently used to determine the localization of
      Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried
      out to examine the serum Egfl7 levels in cancer patients. In addition,
      correlations between Egfl7 expression and clinicopathological features as well as
      prognosis of HCC and breast cancer were also analyzed on the basis of
      immunohistochemistry results.? RESULTS: Egfl7 was differentially expressed in 19
      adult human normal tissues and was overexpressed in all 10 human epithelial tumor
      tissues. The serum Egfl7 level was also significantly elevated in cancer
      patients. The increased Egfl7 expression in HCC correlated with vein invasion,
      absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly,
      upregulation of Egfl7 in breast cancer correlated strongly with TNM stage,
      lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor
      prognosis. ? CONCLUSIONS: Egfl7 is significantly upregulated in human epithelial
      tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial
      tumors, especially HCC and breast cancer.

PMID- 23558934
TI  - Significance of autotaxin activity and overexpression in comparison to soluble
      intercellular adhesion molecule in thyroid cancer.
AB  - BACKGROUND: The objective of this study was to evaluate the role of autotaxin
      (ATX) activity and gene expression compared to soluble intercellular adhesion
      molecule-1 (sICAM-1) in thyroid carcinoma.? PATIENTS AND METHODS: Sixty-five
      patients with thyroid swelling were included. There were 20 cases of simple
      multinodular goiter (group I), 15 cases of follicular adenoma (group II) and 30
      cases of thyroid cancer (group III). Group III was further subdivided into
      negative and positive lymph nodes (group IIIa and IIIb; 22 and 8 cases,
      respectively). sICAM-1 concentration and ATX activity were measured using
      colorimetric enzyme-linked immunosorbent assay (ELISA), while ATX gene expression
      was detected by real-time polymerase chain reaction (PCR).? RESULTS: sICAM-1
      level, ATX activity and gene expression were significantly elevated in patients
      with thyroid carcinoma compared to other groups. The ATX activity showed
      significantly higher sensitivity and specificity than sICAM-1 (100% and 97.1% vs
      93.3% and 88.6%, respectively). Both sICAM-1 and ATX values were significantly
      higher in patients with positive lymph nodes compared to those without lymph node
      involvement (p<0.001). Higher levels of ATX activity and gene expression were
      significantly correlated with larger tumor size and undifferentiated pathological
      subtype in thyroid carcinoma. In this respect, ATX was superior to sICAM-1.?
      CONCLUSION: Our data suggest that ATX activity and gene expression are reliable
      diagnostic and prognostic tools in thyroid carcinoma compared to sICAM-1.

PMID- 23558935
TI  - Expression of ABCG2 associated with tumor response in metastatic colorectal
      cancer patients receiving first-line FOLFOX therapy--preliminary evidence.
AB  - PURPOSE: We retrospectively analyzed ABCG2 expression levels in patients with
      metastatic colorectal cancer (CRC) to investigate the interaction between ABCG2
      expression and the tumor response to oxaliplatin and 5-fluorouracil (FOLFOX).
      METHODS: Forty-three patients with CRC with liver metastasis who received first
      line FOLFOX treatment at our institution between 2008 and 2010 were enrolled.
      ABCG2 expression was assessed by immunohistochemistry. Tumor response was
      determined using the modified Response Evaluation Criteria in Solid Tumors
      criteria. RESULTS: At least 50% tumor shrinkage was observed in 16/43 patients
      (37.2%), including a complete response in 1 patient. According to the intensity
      of ABCG2 expression and the percentage of tumor cells expressing ABCG2, 21 tumors
      displayed high ABCG2 expression. Among these tumors, only 2 (9.5%) exhibited
      partial responses to FOLFOX; conversely, 63.6% of tumors with low ABCG2
      expression (14/22) responded to FOLFOX. Primary and corresponding metastatic
      samples were available for 15 patients, and 13 of the metastatic tumors had
      higher ABCG2 expression than the corresponding primary tumors, but only 1 of
      these tumors responded to FOLFOX (7.7%). CONCLUSIONS: ABCG2 expression is
      associated with the tumor response to FOLFOX in patients with metastatic CRC.
      ABCG2 may be a selective marker for the efficacy of FOLFOX in treating CRC.

PMID- 23558936
TI  - MicroRNA-21 is overexpressed in renal cell carcinoma.
AB  - OBJECTIVE: To identify microRNAs (miRNAs) that are overexpressed in renal cell
      carcinoma (RCC) and characterize the functional role of miR-21. MATERIALS AND
      METHODS: The miRNA expression profiles between RCC tissue and adjacent normal
      tissue were compared using microarray analysis. The differential expression of
      miR-21 was validated by real-time polymerase chain reaction (RT-PCR). 786-O RCC
      cells were transfected with miR-21 mimic, miR-21 inhibitor, or negative controls
      and cell proliferation, apoptosis and cell cycle were examined by MTT assay and
      flow cytometry. The expression of programmed cell death 4 (PDCD4) and tropomyosin
      1 (TPM1) was detected by RT-PCR and Western blot analysis. RESULTS: Compared to
      adjacent normal tissue, 10 human miRNAs were significantly upregulated and 7 were
      downregulated in RCC tissue. RT-PCR confirmed that miR-21 was significantly
      overexpressed in RCC tissue. In vitro expression of miR-21 mimic promoted the
      growth of 786-O cells, whereas miR-21 inhibitor inhibited cell growth by inducing
      apoptosis and cell cycle arrest at S phase. Furthermore, miR-21 mimic or
      inhibitor significantly reduced or increased the expression of PDCD4 and TPM1.
      CONCLUSIONS: MiR-21 is overexpressed in RCC tissue and modulates the growth,
      apoptosis and cell cycle progression of RCC cells and regulates the expression of
      PDCD4 and TPM1.

PMID- 23558937
TI  - Cell proliferation of the primary tumor predicts ipsilateral axillary node
      disease in elderly breast cancer patients.
AB  - The present study investigated whether tumor markers such as cell proliferation
      and steroid receptor status, which have been shown to have relevance for
      important endpoints (relapse-free and overall survival), can also predict
      axillary disease in elderly patients with breast cancer. We evaluated 351
      consecutive elderly women with breast cancer >=70 years of age with estrogen
      receptor (ER)-positive tumors with no palpable axillary nodes, for whom
      information on cell proliferation determined by the 3H-thymidine labeling index
      (TLI) and progesterone receptor (PgR) was available. Patients underwent
      quadrantectomy (70.1%) or quadrantectomy plus radiotherapy (29.9%) without
      axillary node dissection, followed by adjuvant tamoxifen for at least 2 years.
      Univariable (cumulative incidence curves) and multivariable analyses (Fine and
      Gray models) were carried out. After a median follow-up of 16 years, ipsilateral
      axillary relapse was not related to PgR status but was strongly associated with
      tumor cell proliferation in both small (pT1) and large (pT2-4b) tumors. Axillary
      relapse cumulative incidence increased from 1% in patients with low-TLI (<=3%),
      PgR-positive and pT1 tumors to a maximum of 20% in patients with high-TLI, PgR
      negative and pT2-4b tumors. Tumor cell proliferation, determined by TLI at
      primary surgery, is an important predictor of axillary relapse in elderly ER
      positive breast cancer patients and could help to identify patients who should
      undergo axillary surgery.

PMID- 23558938
TI  - TIMP-1 levels and their association with the development and progression of
      systemic malignancies.

PMID- 23558939
TI  - Detection of cytokeratin-20-positive cells in preoperative and postoperative
      blood samples from colorectal cancer patients by real-time RT-PCR.
AB  - BACKGROUND: Detection of circulating cancer cells by reverse transcription
      polymerase chain reaction (RT-PCR) has been studied as a prognostic marker in
      patients with colorectal cancer (CRC) but so far with conflicting results
      regarding specificity and prognostic value. In this study cytokeratin-20 (CK20)
      was evaluated by real-time RT-PCR as a marker for circulating CRC cell detection
      and the influence of surgical tumor resection on the presence of circulating CRC
      cells was analyzed. METHODS: RNA was isolated from the mononuclear cell fraction
      of blood samples taken from 95 CRC patients before and after tumor resection and
      from 23 healthy volunteers and assayed by real-time RT-PCR for CK20 expression.
      RESULTS: Among 23 healthy volunteers one was positive for CK20. Among 95 CRC
      patients, 25 were positive for CK20 before and 23 after surgery. Sixteen patients
      positive before surgery became negative after surgery, while 14 patients negative
      before surgery became positive after surgery. An increase in the proportion of
      CK20-positive samples with increasing stage of disease was observed for
      preoperative but not postoperative blood samples. CONCLUSIONS: Its association
      with clinical stage indicates that CK20 might have prognostic value as a marker
      for detection of circulating CRC cells. Surgical tumor resection can both reduce
      and induce the presence of circulating CRC cells.

PMID- 23558940
TI  - VHL gene alterations in Italian patients with isolated renal cell carcinomas.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of
      the kidney and belongs to the few human tumors known to develop from mutations of
      the VHL tumor suppressor gene. VHL germline mutations are associated with
      hereditary ccRCCs in VHL disease. However, somatic VHL gene defects may also
      occur in sporadic ccRCCs. In this study, we analyzed the frequency and the
      spectrum of VHL gene alterations in 35 Italian patients with sporadic renal cell
      carcinoma (RCC). Tumor-specific intragenic VHL pathogenic mutations were detected
      in 38% (11/29) of the ccRCC patients and 33% (2/6) of the patients with other
      types of RCC. One novel 18-bp in-tandem duplication and 4 previously unreported
      nucleotide changes in the VHL gene were described. Microsatellite analysis showed
      loss of heterozygosity for at least 1 informative marker in 43% (9/21) of the
      ccRCCs and 50% (3/6) of the non-ccRCCs; 5 of the 13 tumors (38%) harboring VHL
      gene alterations also had loss of heterozygosity for at least 1 microsatellite
      marker. Our results confirm that somatic inactivation of the VHL gene may play a
      pivotal role in the tumorigenesis of sporadic ccRCCs in Italian patients and
      suggests that mutation analysis of the VHL gene may be helpful for discriminating
      sporadic, VHL-gene-related ccRCCs from those related to VHL disease. 

PMID- 23558941
TI  - Beclin 1 and its emerging role as a prognostic biomarker in systemic malignancies
      besides bladder carcinomas.

PMID- 23558942
TI  - Hypoxia regulation of phosphokinases and the prognostic value of pAKT in breast
      cancer.
AB  - Tumor hypoxia results in poor treatment response and is an indicator of poor
      outcome in cancer patients. TRIB3 is a hypoxia-upregulated protein involved in
      the ability of breast cancer cells to survive in hypoxic conditions. It is also
      involved in the prognosis of cancer patients, possibly by affecting several
      kinase-signaling pathways. We set out to establish which kinase-signaling
      pathways are regulated by hypoxia and whether these kinases are relevant for
      breast cancer prognosis. Using a phosphokinase antibody array comparing cells
      cultured under hypoxic conditions with those cultured during normoxia, we found
      that the phosphorylation status of ERK1/2, AKT, p70 S6 kinase, Lck and STAT3 was
      altered in both MCF7 and MDA-MB-231 breast cancer cells. Using Western blotting,
      we found that phosphorylated AKT (pAKT) increased in hypoxic conditions.
      Knockdown of TRIB3 attenuated this effect of hypoxia on AKT activation. Both pAKT
      and TRIB3 were expressed in pimonidazole-positive, hypoxic areas of human breast
      cancer tumors. In breast cancer patients significantly lower 5-year disease-free
      survival was observed for the pAKT-positive compared to the pAKT-negative group
      (64.6% vs 86.1%, p=0.03). In conclusion, the phosphorylation status of AKT is
      increased in hypoxic conditions and TRIB3 knockdown attenuates this response.
      Furthermore, pAKT expression denotes a worse prognosis in breast cancer patients.
      The hypoxia-related activation of AKT could explain the resistance to various
      treatments including chemotherapy and radiotherapy.

PMID- 23558943
TI  - A pilot feasibility study for cisplatin plus S-1 for the treatment for advanced
      or recurrent cervical cancer.
AB  - PURPOSE: To evaluate the feasibility of a cisplatin and S-1 combination regimen
      for the treatment for metastatic and recurrent cervical cancers, we performed
      this study prior to a randomized phase III trial to evaluate the clinical
      benefits of a cisplatin and S-1 combination regimen compared with cisplatin
      alone. METHODS: Cisplatin (50 mg/m(2), intravenously on day 1) and S-1 (80-120
      mg/m(2), orally twice a day between days 1 and 14) were administered every 21
      days for 6 cycles in patients with advanced or recurrent uterine cervical cancer.
      RESULTS: A total of 10 patients were enrolled in this trial. A total of 46
      treatment cycles (median 6; range 1-6) were administered. All grade 3 or 4
      hematologic toxicities were recorded in the 6 patients: 2 patients experienced
      anemia, 5 experienced neutropenia, 1 experienced thrombocytopenia, and 2
      experienced febrile neutropenia. All grade 3 non-hematologic toxicities were
      recorded in the 6 patients, and no grade 4 non-hematologic toxicities occurred;
      the most frequent toxicities were hyponatremia in 3 patients, diarrhea in 2
      patients, and infection in 2 patients. The patients with grade 3 diarrhea had
      received prior radiotherapy. All the patients recovered from the toxicities after
      receiving appropriate supportive care, and no treatment-related deaths occurred.
      Five patients (50 %) achieved a partial response, and 1 patient (10 %) had a
      stable disease. CONCLUSION: A cisplatin and S-1 combination regimen was feasible
      for patients with recurrent cervical cancer. Since patients who receive prior
      radiotherapy may experience severe diarrhea, these patients may require an S-1
      dose reduction.

PMID- 23558944
TI  - The elimination of MTC-220, a novel anti-tumor agent of conjugate of paclitaxel
      and muramyl dipeptide analogue, in rats.
AB  - PURPOSE: MTC-220, a conjugate of paclitaxel and muramyl dipeptide analogue, was
      reported to exhibit anti-tumor ability and anti-metastatic effect. The aim of
      present study was to investigate the elimination of MTC-220 and the related
      mechanisms in rats. METHODS: The excretion of MTC-220 and its metabolites in bile
      and urine were determined in rats after intravenous administration at 4 mg/kg.
      Caco-2 cell monolayer, in situ liver perfusion model and in vivo pharmacokinetics
      with selected inhibitors in rats were used to confirm the involvement of hepatic
      transporters in the elimination of MTC-220. The metabolic stability of MTC-220
      was assessed by the incubation with rat liver microsomes and plasma. RESULTS:
      Approximately 72 % of MTC-220 was excreted into bile and less than 0.02 % into
      urine after administration in rats. The Caco-2 cell monolayer was impermeable to
      MTC-220. In in situ liver perfusion model, the hepatic extraction ratio of MTC
      220 was reduced to 40 % of control in the presence of rifampicin, an Oatps
      inhibitor, and the cumulative biliary excretion rates of MTC-220 were reduced to
      52.9, 71.5 and 62.9 % of control when concomitant perfusion with probenecid,
      novobiocin and verapamil, the inhibitors of Mrp2, Bcrp and P-gp, respectively. Co
      administration of rifampicin, probenecid, novobiocin and verapamil with MTC-220
      increased the AUC0-t and decreased the CL of MTC-220 in certain extents in rats.
      MTC-220 remained metabolically intact in rat liver microsomes, but less stable in
      plasma incubation. CONCLUSIONS: In summary, the elimination of MTC-220 was mainly
      through the biliary excretion in unchanged form in rats. Liver transporters
      including Oatps, Mrp2, Bcrp and P-gp might be all involved in the hepatic
      elimination of MTC-220. MTC-220 exhibited the high metabolic stability in liver
      microsomes, but less stable in plasma. The esterases might involve in the
      metabolism of MTC-220 in plasma.

PMID- 23558945
TI  - Coping strategies as psychological risk factor for antenatal anxiety, worries,
      and depression among Greek women.
AB  - A range of psychosocial, medical, and demographic variables may influence
      pregnant women's psychological status. However the association between coping
      strategies, anxiety, worries, and depression during pregnancy is a relatively
      neglected area of research. Therefore, the aim of this study was to examine the
      relationship between coping strategies, antenatal anxiety, pregnancy worries, and
      depressive symptomatology after controlling for the effects of background
      variables. The study sample consisted of 163 pregnant women, with gestational age
      ranging from 11 to 26 weeks, attending antenatal screening at a Greek public
      hospital. Coping strategies were measured with Brief COPE, pregnancy worries were
      measured with Cambridge Worry Scale (CWS), anxiety was assessed using State-Trait
      Anxiety Inventory (STAI-X version), and depression was measured with Center for
      Epidemiologic Studies-Depression scale (CES-D). Pearson's correlation
      coefficients were calculated among all study variables, followed by hierarchical
      multiple linear regression. In the univariate analysis, low annual income,
      unemployment, conception after an IVF treatment, and a previous history of
      miscarriage were associated with anxiety, depression, and worries. Additionally,
      almost all coping strategies (denial, behavioral disengagement, self-blame, self
      distraction, substance use, acceptance, positive reframing, active coping, and
      seeking emotional support) were significantly associated with antenatal anxiety,
      worries, and depression. Linear regression analysis showed that only previous
      history of miscarriage, conception after IVF, as well as denial, behavioral
      disengagement and acceptance coping strategies were significantly related to
      anxiety, worries and depressive symptomatology. The risk factors found in this
      study could help clinicians target anxiety and depression screening to high-risk
      populations of pregnant women. Provision of adequate training for obstetricians
      and midwives in the detection and management of anxiety and depression among
      pregnant women should help to decrease the psychological burden during pregnancy.

PMID- 23558946
TI  - Reassessing the clinical utility of the Patient Health Questionnaire (PHQ)-9 for
      depression screening in prenatal women: a commentary on Sidebottom et al.

PMID- 23558947
TI  - Response to letter from Coronado-Montoya et al.

PMID- 23558948
TI  - The influence of general anxiety and childbirth-specific anxiety on birth
      outcome.
AB  - In the present study, we examined a German sample to determine whether anxiety
      symptoms during pregnancy had an impact on the duration and method of childbirth.
      Data of N = 88 women recruited at the Heidelberg University Hospital were used in
      the analyses. Prepartum anxiety symptoms were assessed with the State-Trait
      Anxiety Inventory (STAI, general anxiety) and the Pregnancy Related Anxiety
      Questionnaire (PRAQ-R, pregnancy-specific anxiety). Obstetric outcome was taken
      from birth records and operationalized by two parameters: the total duration of
      birth (dilation and fetal expulsion) and the incidence of pregnancy or birth
      related interventions (ventouse, planned, and unplanned Cesarean section). The
      data show that childbirth-specific anxiety assessed by the PRAQ-R is an important
      predictor of total birth duration. In contrast, general anxiety measured by the
      STAI had no effect. The incidence of birth intervention was explained by parity.
      Anxiety, however, had no predictive value. In addition to medical factors,
      childbirth-specific anxiety during pregnancy plays an important role in the
      process of childbirth. The findings of the present study point to the need of
      implementing psychological interventions to reduce childbirth-specific anxiety
      and thereby positively influencing birth outcome.

PMID- 23558949
TI  - Three alkaline-earth metal complexes with 3D networks constructed from a 7,7,8,8
      tetracyanoquinodimethane ligand: synthesis, structure and electrochemical
      properties.
AB  - Three new 7,7,8,8-tetracyanoquinodimethane (TCNQ) alkaline-earth metal complexes,
      namely {[M2(TCNQ)3(H2O)6].TCNQ}n (M = Ca (1), Sr (2) and Ba (3)) have been
      synthesized by salt elimination reactions. X-ray crystallographic analysis
      reveals that complexes 1, 2 and 3 are isomorphic featuring a unique 3D structure.
      Cyclic and differential pulse voltammograms for complexes 1-3 show a reversible
      one-electron oxidation and a reversible one-electron reduction within the
      electrochemical window of CH3CN. Their electrochemical HOMO-LUMO gap and
      reversibility are examined.

PMID- 23558950
TI  - E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3.
AB  - The 'activating' E2fs (E2f1-3) are transcription factors that potently induce
      quiescent cells to divide. Work on cultured fibroblasts suggested they were
      essential for division, but in vivo analysis in the developing retina and other
      tissues disproved this notion. The retina, therefore, is an ideal location to
      assess other in vivo adenovirus E2 promoter binding factor (E2f) functions. It is
      thought that E2f1 directly induces apoptosis, whereas other activating E2fs only
      induce death indirectly by upregulating E2f1 expression. Indeed, mouse
      retinoblastoma (Rb)-null retinal neuron death requires E2f1, but not E2f2 or
      E2f3. However, we report an entirely distinct mechanism in dying cone
      photoreceptors. These neurons survive Rb loss, but undergo apoptosis in the
      cancer-prone retina lacking both Rb and its relative p107. We show that while
      E2f1 killed Rb/p107 null rod, bipolar and ganglion neurons, E2f2 was required and
      sufficient for cone death, independent of E2f1 and E2f3. Moreover, whereas E2f1
      dependent apoptosis was p53 and p73-independent, E2f2 caused p53-dependent cone
      death. Our in vivo analysis of cone photoreceptors provides unequivocal proof
      that E2f-induces apoptosis independent of E2f1, and reveals distinct E2f1- and
      E2f2-activated death pathways in response to a single tumorigenic insult.

PMID- 23558951
TI  - Mcl-1 antagonizes Bax/Bak to promote effector CD4(+) and CD8(+) T-cell responses.
AB  - Members of the Bcl-2 family have critical roles in regulating tissue homeostasis
      by modulating apoptosis. Anti-apoptotic molecules physically interact and
      restrain pro-apoptotic family members preventing the induction of cell death.
      However, the specificity of the functional interactions between pro- and anti
      apoptotic Bcl-2 family members remains unclear. The pro-apoptotic Bcl-2 family
      member Bcl-2 interacting mediator of death (Bim) has a critical role in promoting
      the death of activated, effector T cells following viral infections. Although Bcl
      2 is an important Bim antagonist in effector T cells, and Bcl-xL is not required
      for effector T-cell survival, the roles of other anti-apoptotic Bcl-2 family
      members remain unclear. Here, we investigated the role of myeloid cell leukemia
      sequence 1 (Mcl-1) in regulating effector T-cell responses in vivo. We found, at
      the peak of the response to lymphocytic choriomeningitis virus (LCMV) infection,
      that Mcl-1 expression was increased in activated CD4(+) and CD8(+) T cells.
      Retroviral overexpression of Mcl-1-protected activated T cells from death,
      whereas deletion of Mcl-1 during the course of infection led to a massive loss of
      LCMV-specific CD4(+) and CD8(+) T cells. Interestingly, the co-deletion of Bim
      failed to prevent the loss of Mcl-1-deficient T cells. Furthermore, lck-driven
      overexpression of a Bcl-xL transgene only partially rescued Mcl-1-deficient
      effector T cells suggesting a lack of redundancy between the family members. In
      contrast, additional loss of Bax and Bak completely rescued Mcl-1-deficient
      effector T-cell number and function, without enhancing T-cell proliferation.
      These data suggest that Mcl-1 is critical for promoting effector T-cell
      responses, but does so by combating pro-apoptotic molecules beyond Bim. 

PMID- 23558952
TI  - Vital dyes and virtual deaths.

PMID- 23558955
TI  - Extreme tetralogy of Fallot in a dog.
AB  - A four-month-old female Labrador retriever was brought to the Tokyo University of
      Agriculture and Technology Animal Medical Center for examination of its main
      symptoms of cough, tachypnea and exercise intolerance. Upon examination, the dog
      was found to have cyanosis and inadequate growth. Echocardiography revealed
      tetralogy of Fallot. Cardiac catheterization confirmed that the main pulmonary
      artery was completely occluded and that blood flowed from the aorta to the
      pulmonary artery. Accordingly, the animal was diagnosed with extreme tetralogy of
      Fallot. 

PMID- 23558953
TI  - Identification of targetable FGFR gene fusions in diverse cancers.
AB  - Through a prospective clinical sequencing program for advanced cancers, four
      index cases were identified which harbor gene rearrangements of FGFR2, including
      patients with cholangiocarcinoma, breast cancer, and prostate cancer. After
      extending our assessment of FGFR rearrangements across multiple tumor cohorts, we
      identified additional FGFR fusions with intact kinase domains in lung squamous
      cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head
      and neck squamous cell cancer. All FGFR fusion partners tested exhibit
      oligomerization capability, suggesting a shared mode of kinase activation.
      Overexpression of FGFR fusion proteins induced cell proliferation. Two bladder
      cancer cell lines that harbor FGFR3 fusion proteins exhibited enhanced
      susceptibility to pharmacologic inhibition in vitro and in vivo. Because of the
      combinatorial possibilities of FGFR family fusion to a variety of oligomerization
      partners, clinical sequencing efforts, which incorporate transcriptome analysis
      for gene fusions, are poised to identify rare, targetable FGFR fusions across
      diverse cancer types.

PMID- 23558956
TI  - Survey of Coxiella burnetii in ticks collected from dogs in Japan.
AB  - For a survey of Coxiella burnetii, the Q fever agent, ticks infesting companion
      dogs were collected in Aomori, Tochigi, Gifu and Okinawa Prefectures, Japan. A
      total of 261 ticks were collected, and their species were identified
      morphologically. Five tick species were identified: Ixodes ovatus, Haemaphysalis
      concinna, H. flava, H. longicornis and Rhipicephalus sanguineus. Total DNA was
      extracted from them individually followed by real-time PCR to detect a C.
      burnetii-specific gene. The results of real-time PCR were all negative, which
      might suggest a low risk of C. burnetii infection via these ticks and their hosts
      in urban residential areas in Japan. 

PMID- 23558957
TI  - Spontaneous Tyzzer's disease with the central nerve involvement in a newborn
      common marmoset.
AB  - A new-born (8-day-old) male marmoset (Callithrix jacchus) was found dead in a
      zoo. The littermate and parents had no clinical abnormalities. By gross
      observations at necropsy, there were moderate to severe multiple necrotic foci in
      the liver and heart. Histopathological examinations also revealed mild focal
      necrosis with neutrophilic infiltration in the cerebral cortex. By Giemsa stained
      sections, intracytoplasmic bundles of large bacilli were observed in the
      hepatocytes, intestinal epithelial cells, cardiac myocytes and neuronal cells
      around the necrotic lesions. Immunohistochemically, these bacilli were intensely
      positive for rabbit sera against Clostridium piliforme, RT and MSK strains.
      Although Tyzzer's disease has been rarely reported in primates, the central
      nervous system (CNS) lesions by Clostridium piliforme infections are very
      unusual. 

PMID- 23558954
TI  - Diacylglycerol kinase alpha is a critical signaling node and novel therapeutic
      target in glioblastoma and other cancers.
AB  - Although diacylglycerol kinase alpha (DGKalpha) has been linked to several
      signaling pathways related to cancer cell biology, it has been neglected as a
      target for cancer therapy. The attenuation of DGKalpha activity via DGKalpha
      targeting siRNA and small-molecule inhibitors R59022 and R59949 induced caspase
      mediated apoptosis in glioblastoma cells and in other cancers, but lacked
      toxicity in noncancerous cells. We determined that mTOR and hypoxia-inducible
      factor-1alpha (HIF-1alpha) are key targets of DGKalpha inhibition, in addition to
      its regulation of other oncogenes. DGKalpha regulates mTOR transcription via a
      unique pathway involving cyclic AMP. Finally, we showed the efficacy of DGKalpha
      inhibition with short hairpin RNA or a small-molecule agent in glioblastoma and
      melanoma xenograft treatment models, with growth delay and decreased vascularity.
      This study establishes DGKalpha as a central signaling hub and a promising
      therapeutic target in the treatment of cancer. 

PMID- 23558958
TI  - Value of the 13C-urea breath test for detection of gastric Helicobacter spp.
      infection in dogs undergoing endoscopic examination.
AB  - Urea breath test (UBT) using an infrared spectral analyzer is widely used for non
      invasive and rapid detection of gastric Helicobacter spp. in human, but not
      veterinary medicine. The main purposes of this study were to determine the
      reference range of the UBT in dogs and to evaluate its clinical usefulness. To
      address the first aim, 6 healthy laboratory beagles were subjected to UBT and
      upper gastrointestinal endoscopy. Gastric endoscopic biopsy samples from the
      antrum, corpus and fundus were examined for Helicobacter spp. by polymerase chain
      reaction (PCR) testing, rapid urease test (RUT), histology and cytology.
      Amoxicillin, metronidazole and omeprazole were given to infected dogs for 14
      days, and dogs that became Helicobacter-negative were used to determine the
      reference range for UBT. To address the second aim, 32 canine patients underwent
      UBT before upper gastrointestinal endoscopy, and the sensitivity and specificity
      of UBT were calculated based on our newly determined reference range using PCR as
      the gold standard for detection of Helicobacter spp. Initially, all 6 laboratory
      beagles were infected in all gastric regions and became uninfected after
      eradication. The mean +/- 2 SD UBT value after eradication was 0.6 +/- 1.80/00,
      and the reference range for UBT was determined to be less than 2.50/00. UBT was
      completed successfully in 27 patients. Using our reference range, UBT displayed
      89% (16/18) sensitivity and 89% (8/9) specificity, indicating that UBT was quite
      useful for the detection of gastric Helicobacter spp. infection in dogs. 

PMID- 23558959
TI  - With the help of a foreign ally: biopharmaceutical innovation in India after
      TRIPS.
AB  - This article investigates the implications of the Agreement on Trade-Related
      Aspects of Intellectual Property Rights (TRIPS), which reached full-fledged
      implementation in 2005, for the patenting activity of Indian biopharmaceutical
      companies. The Indian biopharmaceutical industry is well-known for its generic
      producers, whose business models capitalize on the opportunity to reverse
      engineer patented compounds and produce them at low costs through process
      innovation. By strengthening intellectual property rights, TRIPS determined a
      major regulative change, which presents the characteristics of an institutional
      shock. The examination of the patenting and alliance activity of 123 Indian
      biopharmaceutical firms between 1999 and 2009 reveals two important insights.
      First, the innovation outcome of Indian biopharmaceuticals has sharply increased
      during the transition to TRIPS-compliant regulation, suggesting that Indian
      companies have been capable and willing to transit from an imitation-based to an
      innovation-based business model. Second, those biopharmaceutical firms holding
      cross-border alliances to foreign partners have proved significantly more
      successful at enhancing their innovative capability. This research delivers a
      multifold contribution to the policy debate surrounding the enforcement of TRIPS
      in emerging economies. First, it suggests that such regulatory change may have
      encouraged biopharmaceutical innovation in India, despite the sceptical voices
      who did not foresee any benefits because of inherent inertia of the industry.
      Second, by arguing and testing the advantages of foreign partnerships, this
      research highlights that the much feared return of pharmaceutical foreign
      companies to India could instead favour adaptation to institutional change.
      Implications for Indian public health are particularly critical. The impact of
      TRIPS on drug pricing and on the capability--and willingness--of Indian
      biopharmaceuticals to invest in local health conditions are two crucial points of
      discussion.

PMID- 23558960
TI  - Health insurance selection in Chile: a cross-sectional and panel analysis.
AB  - In Chile, workers are mandated to choose either public or private health
      insurance coverage. Although private insurance premiums depend on health risk,
      public insurance premiums are solely linked to income. This structure implies
      that individuals with higher health risks may tend to avoid private insurance,
      leaving the public insurance system responsible for their care. This article
      attempts to explore the determinants of health insurance selection (private vs
      public) by individuals in Chile and to test empirically whether adverse selection
      indeed exists. We use panel data from Chile's 'Encuesta de Proteccion Social'
      survey, which allows us to control for a rich set of individual observed and
      unobserved characteristics using both a cross-sectional analysis and fixed-effect
      methods. Results suggest that age, sex, job type, income quintile and self
      reported health are the most important factors in explaining the type of
      insurance selected by individuals. Asymmetry in insurance mobility caused by
      restrictions on pre-existing conditions may explain why specific illnesses have
      an unambiguous relationship with insurance selection. Empirical evidence tends to
      indicate that some sorting by health risk and income levels takes place in Chile.
      In addition, by covering a less healthy population with higher utilization of
      general health consultations, the public insurance system may be incurring
      disproportionate expenses. Results suggest that if decreasing segmentation and
      unequal access to health services are important policy objectives, special
      emphasis should be placed on asymmetries in the premium structure and inter
      system mobility within the health care system. Preliminary analysis of the impact
      of the 'Garantias Explicitas de Salud' plan (explicit guarantees on health care
      plan) on insurance selection is also considered. 

PMID- 23558961
TI  - Muscle size, activation, and coactivation in adults with cerebral palsy.
AB  - INTRODUCTION: Muscle weakness is present in the paretic limbs of individuals with
      cerebral palsy (CP). We aimed to determine what neuromuscular factors contribute
      to weakness in adults with CP during isometric maximal voluntary contractions
      (iMVCs). METHODS: Gastrocnemius anatomical cross-sectional area (ACSA) and
      agonist and antagonist activation were measured in 11 CP and 11 control adult men
      during plantarflexion iMVC. RESULTS: Plantarflexion iMVC torque of the paretic
      leg was 42% and 52% less than in the non-paretic and control limbs, respectively.
      The paretic gastrocnemius ACSA was smaller than in the control group only.
      Paretic agonist activation was less than the non-paretic and control groups,
      whereas antagonist coactivation was higher. Multiple regression analysis revealed
      muscle activation accounted for 57% of variation in paretic plantarflexion iMVC
      torque. CONCLUSIONS: In individuals with CP, muscle weakness in the paretic limb
      is attributed primarily to impaired neural activation and, to a lesser degree,
      ACSA.

PMID- 23558962
TI  - microRNAs in uterine sarcomas and mixed epithelial-mesenchymal uterine tumors: a
      preliminary report.
AB  - Uterine sarcomas and mixed epithelial-mesenchymal uterine tumors are a
      heterogeneous group of rare tumors for which there are very few diagnostic
      markers available. As aberrant microRNA (miRNA) expression patterns represent
      putative diagnostic cancer markers, we aimed to identify miRNA expression
      profiles of the major uterine sarcoma subtypes and mixed epithelial-mesenchymal
      tumors of the uterus. Eighty-eight miRNAs were assessed by quantitative RT-PCR in
      cancerous and non-cancerous tissue samples collected from 29 patients with
      endometrial sarcoma, leiomyosarcoma, and mixed epithelial-mesenchymal tumors.
      Tumor and control samples significantly (P < 0.05) differed in the expression of
      miR-23b, miR-1, let-7f, and let-7c in endometrial sarcomas, and miR-1, let-7c,
      miR-133b, let-7b, miR-143, let-7a, let-7d, let-7e, let-7g, miR-222, let-7i, and
      miR-214 in mixed epithelial-mesenchymal tumors. All the significantly changed
      miRNAs were down-regulated in the malignant tissues as compared to their normal
      counterparts. This may suggest their tumor suppressor role in these malignancies.
      No statistically significant changes in miRNA expression levels were found
      between leiomyosarcoma tumors and controls. The identified miRNAs warrant further
      studies as valuable candidate markers for the differential diagnosis of uterine
      sarcomas from benign uterine lesions and between uterine sarcoma subtypes.

PMID- 23558963
TI  - Clinical and prognostic significance of Yes-associated protein in colorectal
      cancer.
AB  - The Hippo signaling pathway is a critical regulator of organ size control during
      development, and its deregulation is associated with cancers. Acting downstream
      of this pathway, Yes-associated protein (YAP) was implicated in tumorigenesis.
      The present study aimed to explore the expression patterns and clinical
      significance of YAP in human colorectal cancer (CRC). In addition, we
      investigated the relationship between YAP expression and Wnt/beta-catenin pathway
      activation in CRC. A total of 139 cases of CRC tissues were investigated by
      immunohistochemistry for the expression of YAP, cyclin D1, and beta-catenin. The
      association between YAP expression and clinicopathologic features was analyzed.
      Our results showed that YAP was overexpressed in 52.5 % (73/139) cases of CRC and
      predominantly presented in the nucleus. There was an excellent correlation
      between YAP expression and pTNM stage (p = 0.0024). YAP expression in CRC was
      significantly correlated with nodal status (p = 0.0034), tumor status (p =
      0.0382), and cyclin D1 overexpression (p < 0.0001). Importantly, YAP expression
      was associated with short overall survival (p < 0.001). Furthermore, patients
      with YAP-positive and nuclear beta-catenin-positive profiles had worse overall
      survival. Univariate and multivariate analyses revealed that YAP expression was
      an independent prognostic indicator of CRC (p = 0.0207). Our results indicated
      that YAP overexpression contributed to the tumorigenesis and played a pivotal
      role in the progression in CRC, and the interaction of YAP and Wnt/beta-catenin
      pathways needs further exploration.

PMID- 23558964
TI  - CYP2D6 T188C variant is associated with lung cancer risk in the Chinese
      population.
AB  - The CYP2D6 gene has been suggested to play an important role in the pathogenesis
      of lung cancer. However, the results have been inconsistent. In this study, we
      performed a meta-analysis to clarify the association of CYP2D6 T188C variant with
      lung cancer. Published literature from PubMed, Embase, Chinese National Knowledge
      Infrastructure and Wanfang data were retrieved. Pooled odds ratio (OR) with 95 %
      confidence interval (CI) was calculated using fixed- or random-effects model. A
      total of nine studies (1,516 lung cancer cases and 1,950 controls) for CYP2D6
      T188C variant were included in the meta-analysis. The meta-analysis indicated
      that compared with CYP2D6 TT genotype, non-TT genotype (CC or CT) was
      significantly associated with lung cancer in the Chinese (OR = 1.61, 95 % CI =
      1.38-1.87, p < 0.001), with no evidence of between-study heterogeneity (I (2) =
      0.0 %, p = 0.991). The sensitivity analysis indicated that the association was
      stable and no publication bias was detected. The present meta-analysis supported
      the positive association of CYP2D6 T188C variant with lung cancer in the Chinese.
      Further large-scale studies with the consideration for gene-gene/gene-environment
      interactions should be conducted to investigate the association.

PMID- 23558965
TI  - Telomerase as a useful target in cancer fighting-the breast cancer case.
AB  - Telomerase was initially considered as a relevant factor distinguishing cancer
      from normal cells. During detailed studies, it appeared that its expression and
      activity is not only limited to cancer cells however, but in this particular
      cells, the telomerase is much more abundant. Thus, it has become a very promising
      target for an anticancer therapy. It was revealed in many studies that regulation
      of telomerase is a multifactorial process in mammalian cells, involving
      regulation of expression of telomerase subunits coding genes, post-translational
      protein-protein interactions, and protein phosphorylation. Numerous proto
      oncogenes and tumor suppressor genes are engaged in this mechanism, and the
      complexity of telomerase control is studied in the context of tumor development
      as well as aging. Additionally, since numerous studies reveal a correlation
      between short telomeres and increased genome instability or cell mortality, the
      telomerase control appears to be one of the crucial factors to study in order to
      improve the cancer diagnostics and therapy or prevention. Interestingly, almost
      100 % of adenocarcinoma, including breast cancer cells, expresses telomerase
      which makes it a good target for telomerase-related therapy. Additionally,
      telomerase is also supposed to be associated with drug resistance. Thus,
      targeting the enzyme might result in attenuation of this phenomenon. Moreover,
      since stem cells existence was reported, it must be considered whether targeting
      telomerase can bring some serious side effects and result in stem cells viability
      or their regenerative potential decrease. Thus, we review some molecular
      mechanisms engaged in therapy based on targeting telomerase in breast cancer
      cells.

PMID- 23558966
TI  - XRCC3 T241M polymorphism is associated risk of hepatocellular carcinoma in the
      Chinese.
AB  - The X-ray repair cross-complementing group 3 (XRCC3) gene has been suggested to
      play an important role in the pathogenesis of hepatocellular carcinoma (HCC).
      However, the results have been inconsistent. In this study, we performed a meta
      analysis to clarify the association of XRCC3 Thr241Met variant with HCC. The
      published literature from PubMed, Chinese National Knowledge Infrastructure, and
      Wan Fang data was retrieved. Pooled odds ratio (OR) with 95 % confidence interval
      (CI) was calculated using fixed or random effects model. A total of five studies
      (1,531 HCC cancer cases and 1,952 controls) for XRCC3 Thr241Met variant were
      included in the meta-analysis. The meta-analysis showed that XRCC3 Thr241Met
      variant was associated with HCC risk under homogeneous codominant model (OR =
      3.99, 95 % CI = 1.74-9.13) and recessive model (OR = 5.22, 95 % CI = 3.65-7.48),
      but not under heterogeneous codominant model (OR = 1.18, 95 % CI = 0.68-2.05) and
      dominant model (OR = 1.37, 95 % CI = 0.73-2.57). Subgroup analysis by ethnicity
      suggested that XRCC3 Thr241Met variant was associated with HCC risk in Chinese
      population, but not in Pakistani population. The present meta-analysis supported
      the positive association of XRCC3 Thr241Met variant with HCC in the Chinese.
      Further large-scale studies with the consideration for gene-gene/gene-environment
      interactions should be conducted to investigate the association.

PMID- 23558967
TI  - Bone marrow fat composition as a novel imaging biomarker in postmenopausal women
      with prevalent fragility fractures.
AB  - The goal of this magnetic resonance (MR) imaging study was to quantify vertebral
      bone marrow fat content and composition in diabetic and nondiabetic
      postmenopausal women with fragility fractures and to compare them with
      nonfracture controls with and without type 2 diabetes mellitus. Sixty-nine
      postmenopausal women (mean age 63 +/- 5 years) were recruited. Thirty-six
      patients (47.8%) had spinal and/or peripheral fragility fractures. Seventeen
      fracture patients were diabetic. Thirty-three women (52.2%) were nonfracture
      controls. Sixteen women were diabetic nonfracture controls. To quantify vertebral
      bone marrow fat content and composition, patients underwent MR spectroscopy (MRS)
      of the lumbar spine at 3 Tesla. Bone mineral density (BMD) was determined by dual
      energy X-ray absorptiometry (DXA) of the hip and lumbar spine (LS) and
      quantitative computed tomography (QCT) of the LS. To evaluate associations of
      vertebral marrow fat content and composition with spinal and/or peripheral
      fragility fractures and diabetes, we used linear regression models adjusted for
      age, race, and spine volumetric bone mineral density (vBMD) by QCT. At the LS,
      nondiabetic and diabetic fracture patients had lower vBMD than controls and
      diabetics without fractures (p = 0.018; p = 0.005). However, areal bone mineral
      density (aBMD) by DXA did not differ between fracture and nonfracture patients.
      After adjustment for age, race, and spinal vBMD, the prevalence of fragility
      fractures was associated with -1.7% lower unsaturation levels (confidence
      interval [CI] -2.8% to -0.5%, p = 0.005) and +2.9% higher saturation levels (CI
      0.5% to 5.3%, p = 0.017). Diabetes was associated with -1.3% (CI -2.3% to -0.2%,
      p = 0.018) lower unsaturation and +3.3% (CI 1.1% to 5.4%, p = 0.004) higher
      saturation levels. Diabetics with fractures had the lowest marrow unsaturation
      and highest saturation. There were no associations of marrow fat content with
      diabetes or fracture. Our results suggest that altered bone marrow fat
      composition is linked with fragility fractures and diabetes. MRS of spinal bone
      marrow fat may therefore serve as a novel tool for BMD-independent fracture risk
      assessment. 

PMID- 23558968
TI  - Age-related histologic changes in human nasal cartilage.
AB  - IMPORTANCE: Understanding age-related changes is important when considering
      cartilage-based implants or grafts during rhinoplasty and nasal reconstructive
      surgery. OBJECTIVE: To characterize the cellular and architectural changes in
      human nasal cartilage with aging. DESIGN: Laboratory study. PARTICIPANTS: Nasal
      septal cartilage was harvested from 50 consecutive patients undergoing
      septoplasty, rhinoplasty, or septorhinoplasty. INTERVENTION: Cartilage specimens
      were stained with hematoxylin-eosin (H&E) and safranin O for cartilage. MAIN
      OUTCOME MEASURES: A modified Mankin histologic grading scale was used to analyze
      each cartilage sample for H&E findings and safranin O staining. Higher H&E scores
      indicated more degenerative changes, while higher safranin O scores indicated
      reductions in proteoglycan content within the cartilage matrix, representing
      decreased active chondrocyte activity. Correlation between H&E and safranin O
      scores and patient age was determined. RESULTS: There was positive correlation
      between safranin O staining scores and age, with higher scores seen with
      advancing age (P = .01). A linear regression best-fit equation was determined to
      calculate a potential safranin O staining score for a given age. CONCLUSIONS AND
      RELEVANCE: We have quantitatively determined that advancing age is positively
      correlated with reductions in cartilage proteoglycan content and active cartilage
      growth. This finding not only enhances our current understanding of the natural
      changes that occur in cartilage with aging but may also affect surgical decision
      making when cartilage grafting is considered during functional, reconstructive,
      and aesthetic rhinoplasty. LEVEL OF EVIDENCE: NR.

PMID- 23558969
TI  - Endoscopic closure of acute esophageal perforations.
AB  - Esophageal leak is a life-threatening problem that can result from spontaneous
      rupture of the esophagus, cancer, anastomotic dehiscence after surgery, or as a
      complication of endoscopy. During the last decade, developments in the minimally
      invasive endoluminal approach to the management of esophageal leaks include
      utilization of endoscopy not only for diagnosis but also for closure of leaks
      with clips or sutures, bypass of the leaks with stents, and/or endoluminal
      drainage of mediastinal infection. The aim of this review is to summarize recent
      advances and the principles of endoscopic management of acute esophageal
      perforations.

PMID- 23558970
TI  - Learning and memory: remembrance of things similar...

PMID- 23558971
TI  - Will the European Union's new tobacco tax legislation lead to reductions in
      smoking prevalence? Evidence from a quasi-experiment in Spain.
AB  - INTRODUCTION: The European Union (EU) requires member states to apply minimum
      taxes on manufactured cigarettes. One such tax has operated in Spain since 2006.
      This study evaluates the impact of this reform of the tax regime on manufactured
      cigarette prices and on smoking prevalence, drawing implications for European
      tobacco tax policy. METHODS: Quasi-experimental design with treatment and control
      territories. We analyzed series for prices before and after the reform and used
      cross-sectional health surveys to implement differences-in-differences estimators
      for smoking prevalence. RESULTS: Under the minimum tax regime, prices increased
      three times faster in the treatment territory. However, the new regime did not
      affect smoking prevalence among males, either shortly after its enactment or 3
      years hence. For women, we find no significant effects on prevalence in the short
      run, and point estimates ranging between -3.36% and -4.3% 3 years hence, although
      only one of these is statistically significant. CONCLUSIONS: The new tax regime
      affected cigarette prices in the intended direction. However, we find only weak
      evidence for a reduction in prevalence among women. The availability of cheap,
      fine-cut tobacco appears to be the most likely cause for the poor results in
      terms of smoking prevalence. EU member states that have introduced a minimum tax
      on manufactured cigarettes might achieve little in terms of reductions in smoking
      prevalence if they allow a tax gap between fine-cut tobacco and manufactured
      cigarettes. In this sense, it is unfortunate that EU legislation consecrates a
      differential treatment for the two products.

PMID- 23558972
TI  - Changing blood lead levels and oxidative stress with duration of residence among
      Taiwan immigrants.
AB  - Immigrants lack appropriate health care access and other resources needed to
      reduce their exposure to preventable environmental health risks. Little is known
      about the impact of lead exposure and oxidative stress among immigrants. Thus,
      this study was to examine the differences between the blood lead levels (BLLs)
      and oxidative stress levels of immigrants and non-immigrants, and to investigate
      the determinants of increased BLLs or oxidative stress levels among immigrants.
      We collected demographic data of 239 immigrant women and 189 non-immigrant women
      who resettled in the central area of Taiwan. Each study participant provided
      blood samples for genotyping and for measuring blood metal levels and oxidative
      stress. Recent immigrants were at risk for elevated BLLs. Decreased BLLs,
      malondialdehyde (MDA), and increased blood selenium levels were significantly
      associated with duration of residence in Taiwan. Elevated BLLs and MDA in recent
      immigrants may serve as a warning sign for the health care system. The nation's
      health will benefit from improved regulation of living environments, thereby
      improving the health of immigrants. 

PMID- 23558973
TI  - Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.
AB  - The role of mast cells (MCs) in allergic reactions and parasitic infections is
      well established. Their involvement in host immune response against bacterial and
      viral infections is reported. In this study, investigation is made to determine
      if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with
      crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained
      intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting
      ECA positive for CPV-2 and negative for Canine distemper virus and Canine
      coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with
      inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The
      average total MCC per high-power field in ECA (40.8 +/- 2.2) and IBD (24.7 +/-
      2.1) was significantly higher (P < .05) than in the control (3.4 +/- 0.6).
      Although not significant (P > .05), MCC was also higher in ECA than in IBD. The
      present study for the first time has documented significantly increased MCs in
      CPV-2-associated ECA as was previously reported for IBD, showing that MCs may
      also play an important role in CPV-2-associated ECA. Further studies involving
      more CPV-infected dogs are recommended to substantiate the findings. 

PMID- 23558976
TI  - The influence of body mass index and low-grade systemic inflammation on thyroid
      hormone abnormalities in patients with type 2 diabetes.
AB  - Previous reports highlight the role of systemic inflammation in the genesis of
      non-thyroidal illness syndrome and type 2 diabetes mellitus (T2DM). Our objective
      was to assess whether body mass index and the low-grade systemic inflammation
      would be associated with changes in thyroid hormone metabolism in patients with
      type 2 diabetes. This was a cross-sectional study of 104 subjects; 52 patients
      with type 2 diabetes and 52 in a control group, paired by age, gender and body
      mass index. We measured total (T) and free (F) thyroxine (T4) and
      triiodothyronine (T3), reverse T3 (rT3), the ratios FT3/rT3, FT3/FT4 and FT4/rT3,
      clinical parameters (age, gender, diabetes duration and complications, body mass
      index, waist circumference, hypertension, HbA1c), and high sensitivity C-reactive
      protein. Patients with DM presented lower levels of TT4 (p=0.006), TT3 (p<0.001)
      and FT3 (p<0.001) and higher of FT4 (p<0.001), waist circumference (p=0.047) and
      C-reactive protein (p<0.001). Body mass index was inversely correlated with FT4
      (p=0.036) and TT3 (p=0.008). C-reactive protein was positively correlated with
      rT3 (p=0.001) and inversely with FT4/rT3 (p<0.001) and FT3/rT3 (p=0.014). Body
      mass index was an independent predictor for FT4 (B=-0.011, p=0.029) and TT3
      levels (B=-1.118, p=0.003). Inflammation predicted the FT4/rT3 ratio (B=-0.190,
      p<0.001). C-reactive protein (B=0.235, p<0.001) and body mass index (B=-0.008,
      p=0.047) were independent predictors for rT3. In conclusion, type 2 diabetes was
      associated with a low T3 state. Body mass index and the low-grade systemic
      inflammation are related to the non-thyroidal illness syndrome in these patients,
      possibly by altering the activity of peripheral deiodinases. 

PMID- 23558974
TI  - Principles for valid histopathologic scoring in research.
AB  - Histopathologic scoring is a tool by which semiquantitative data can be obtained
      from tissues. Initially, a thorough understanding of the experimental design,
      study objectives, and methods is required for the pathologist to appropriately
      examine tissues and develop lesion scoring approaches. Many principles go into
      the development of a scoring system such as tissue examination, lesion
      identification, scoring definitions, and consistency in interpretation. Masking
      (aka "blinding") of the pathologist to experimental groups is often necessary to
      constrain bias, and multiple mechanisms are available. Development of a tissue
      scoring system requires appreciation of the attributes and limitations of the
      data (eg, nominal, ordinal, interval, and ratio data) to be evaluated. Incidence,
      ordinal, and rank methods of tissue scoring are demonstrated along with key
      principles for statistical analyses and reporting. Validation of a scoring system
      occurs through 2 principal measures: (1) validation of repeatability and (2)
      validation of tissue pathobiology. Understanding key principles of tissue scoring
      can help in the development and/or optimization of scoring systems so as to
      consistently yield meaningful and valid scoring data. 

PMID- 23558977
TI  - Long-term health-related quality of life of stroke survivors and their spousal
      caregivers.
AB  - Because treatment for stroke has improved, individuals are living longer with the
      effects of a stroke. The resulting long-term impairment can affect both stroke
      survivors' and their caregivers' health-related quality of life (HRQOL). Few
      studies have examined the HRQOL of stroke survivors and their caregivers greater
      than 2 years poststroke. The stroke survivors and their spousal caregivers (n =
      30 dyads) who had previously completed a 12-month study after discharge from
      inpatient rehabilitation were assessed at 3-5 years poststroke. The HRQOL and
      related outcomes were measured for stroke survivors and caregivers. Data from
      baseline to 12 months were used in conjunction with data from this study. Linear
      mixed models were used to analyze the change in repeated measures over time.
      Multiple linear regression was used to analyze the relationship of generic HRQOL
      to related psychosocial outcomes. The stroke survivors were an average of 4.68
      years poststroke. The mean age for stroke survivors and caregivers was 70.8 and
      64.9 years, respectively. Most stroke survivors were men (80%) and non-Hispanic
      White (70%). Among stroke survivors, depression decreased from baseline to 12
      months (p = .04) but increased from 12 months to the end of follow-up (p = .003).
      The caregivers' depression decreased from baseline to all time points (p = .015).
      Stroke-specific HRQOL showed statistically significant (p < .03) decreases
      between 12 months and end of follow-up. Increased number of illnesses and older
      age were associated with caregivers' lower physical HRQOL score (p = .004).
      Higher depression was associated with lower mental HRQOL score for both
      caregivers and stroke survivors (p = .003 and p = .011, respectively). Both
      stroke survivors and caregivers continue to experience negative stroke-related
      health outcomes for many years after the initial stroke; some of these outcomes
      even worsen over time. These findings illustrate the need for ongoing
      psychological and medical evaluation for both long-term stroke survivors and
      caregivers. Development and testing of targeted behavioral interventions are also
      warranted.

PMID- 23558978
TI  - Symptoms associated with mild traumatic brain injury/concussion: the role of
      bother.
AB  - Traumatic brain injury (TBI) affects 1.4 million Americans annually, and mild TBI
      (MTBI) accounts for approximately 75% of those injured. For those with mild
      injury who seek treatment in an emergency department, there is inconsistency in
      the management and follow-up recommendations. Approximately, 38% of patients
      treated in the emergency department for MTBI are discharged with no
      recommendations for follow-up. In addition, there are an unknown number of
      persons with MTBI who do not seek healthcare after their injury. Persons with
      MTBI are, for the most part, managing their concussion symptoms on their own. The
      purpose of this study was to describe the symptom experience for persons with
      mild TBI and identify whether there was an association between being bothered by
      symptoms and self-management of symptoms. The sample for this study included 30
      persons with MTBI and a 30-person comparison group. Results indicate that persons
      within 3 months of their MTBI report an average of 19 symptoms, whereas the
      comparison group reported six symptoms, and that the most frequently reported
      symptoms are not always the symptoms rated as most severe or most bothersome.
      Persons with MTBI reported their most common symptoms to be headache (n = 25,
      83%), feeling tired (n = 24, 80%), difficulty thinking and being irritable (each
      n = 22, 73%), dizziness, trouble remembering, and being forgetful (each n = 21,
      70%). There is a significant relationship between overall reports of being
      bothered by symptoms and the use of symptom management strategies (F = 8.322, p =
      .008). Persons are more likely to use symptom management strategies when they are
      bothered by the symptoms. Nurses can assist with symptom self-management by
      providing simple symptom management strategies to assist with the symptom
      management process. Early symptom management for the MTBI population may improve
      the outcomes such as return to work and role functions, for this population.

PMID- 23558979
TI  - A novel in-frame deletion of the RUNX2 gene causes a classic form of
      cleidocranial dysplasia.
AB  - The runt-related transcription factor 2 (RUNX2) is a physiological regulatory
      gene implicated in the development of cleidocranial dysplasia (CCD). Molecular
      analysis of the RUNX2 gene in a 2-year-old boy with a diagnosis of CCD
      demonstrated a heterozygous in-frame 9-bp deletion (c.593_601delCCTTGACCA,
      corresponding to the amino-acid deletion p.DeltaTLT198_200). Transcription
      activity of the DeltaTLT198_200 mutant decreased in a similar degree to that of
      the L199F mutant, which was previously reported in the case with classic CCD.
      Atomic model assessment demonstrated that the DeltaTLT198_200 mutation abolished
      the heterodimerization of the RUNX2 protein with the partner subunit,
      polyomavirus enhancer-binding protein 2beta (PEBP2beta). Destruction of
      RUNX2/PEBP2beta heterodimerization activity appears to impair the function of the
      RUNX2 protein and cause the disease. 

PMID- 23558980
TI  - Heavy metals and organic compounds contamination in soil from an e-waste region
      in South China.
AB  - Heavy metals and persistent organic pollutants polychlorinated biphenyls (PCBs)
      and polybrominated diphenyl ethers (PBDEs) were analyzed in 34 surface soil
      samples collected from farmland and 7 soil or dust samples collected from the
      workshops in South China, where e-waste was dismantled using primitive
      techniques. The results show that Cd, Cu and Hg were the most abundant metals, in
      particular Cd pollution was serious in farmland soils, and the median
      concentrations in farmland soils were beyond the environmental quality standard
      for soils (China Grade II). A correlation between Cd, Cu, Zn, Pb and PCBs or
      PBDEs was significant indicating similar sources. Among the PCB congeners, high
      relative similarity was observed between the e-waste dump site soil (EW1) and
      Aroclor 1254, implying that the technical product Aroclor 1254 was one of the
      major sources of PCB contamination. High concentrations of PCBs in workshop dusts
      (D2 and D3) (1958 and 1675 MUg kg(-1)) demonstrated that the workshops
      dismantling electrical wires and cables, electrical motors, compressors and
      aluminum apparatus containing PCBs in lubricants represent strong PCB emission
      sources to this area. Principal component analysis (PCA) and PBDE homologue
      patterns verify that farmland soils surrounding the e-waste recycling sites were
      enriched with lower brominated congeners, and the major source of PBDEs in dust
      samples might potentially be associated with the extensive use of deca-mix
      technical products as a flame retardant. The difference between e-waste soils,
      dusts and farmland soils can be observed in the PCA score plot of PCBs and PBDEs,
      and E-waste soils and dusts exhibited more diversity than farmland soils.
      Furthermore, a prediction of the particular kinds of pollution from different
      recycling activities through the analysis of each contamination and the
      connections between them was investigated.

PMID- 23558981
TI  - The black carbon story: early history and new perspectives.
AB  - A number of recent studies have suggested that black carbon (BC), the light
      absorbing fraction of soot, is next to CO2 one of the strongest contributors to
      the global climate change. BC heats the air, darkens the snow and ice surfaces
      and could contribute to the melting of Arctic ice, snowpacks, and glaciers.
      Although soot is the oldest known pollutant its importance in climate
      modification has only been recently recognized. In this article, we trace the
      historical developments over about three decades that changed the view of the
      role of BC in the environment, from a pollutant of marginal importance to one of
      the main climate change agents. We also discuss some of the reasons for the
      initial lack of interest in BC and the subsequent rigorous research activity on
      the role of aerosols in climate change. 

PMID- 23558982
TI  - QTL analysis of the spring wheat "Chapio" identifies stable stripe rust
      resistance despite inter-continental genotype * environment interactions.
AB  - Chapio is a spring wheat developed by CIMMYT in Mexico by a breeding program that
      focused on multigenic resistances to leaf rust and stripe rust. A population
      consisting of 277 recombinant inbred lines (RILs) was developed by crossing
      Chapio with Avocet. The RILs were genotyped with DArT markers (137 randomly
      selected RILs) and bulked segregant analysis conducted to supplement the map with
      informative SSR markers. The final map consisted of 264 markers. Phenotyping
      against stripe rust was conducted for three seasons in Toluca, Mexico and at
      three sites over two seasons (total of four environments) in Sichuan Province,
      China. Significant loci across the two inter-continental regions included
      Lr34/Yr18 on 7DS, Sr2/Yr30 on 3BS, and a QTL on 3D. There were significant
      genotype * environment interactions with resistance gene Yr31 on 2BS being
      effective in most of the Toluca environments; however, a late incursion of a
      virulent pathotype in 2009 rendered this gene ineffective. This locus also had no
      effect in China. Conversely, a 5BL locus was only effective in the Chinese
      environments. There were also complex additive interactions. In the Mexican
      environments, Yr31 suppressed the additive effect of Yr30 and the 3D locus, but
      not of Lr34/Yr18, while in China, the 3D and 5BL loci were generally not additive
      with each other, but were additive when combined with other loci. These results
      indicate the importance of maintaining diverse, multi-genic resistances as Chapio
      had stable inter-continental resistance despite the fact that there were QTLs
      that were not effective in either one or the other region. 

PMID- 23558983
TI  - Strategy for exploiting exotic germplasm using genetic, morphological, and
      environmental diversity: the Aegilops tauschii Coss. example.
AB  - Hexaploid bread wheat evolved from a rare hybridisation, which resulted in a loss
      of genetic diversity in the wheat D-genome with respect to the ancestral donor,
      Aegilops tauschii. Novel genetic variation can be introduced into modern wheat by
      recreating the above hybridisation; however, the information associated with the
      Ae. tauschii accessions in germplasm collections is limited, making rational
      selection of accessions into a re-synthesis programme difficult. We describe
      methodologies to identify novel diversity from Ae. tauschii accessions that
      combines Bayesian analysis of genotypic data, sub-species diversity and
      geographic information that summarises variation in climate and habitat at the
      collection point for each accession. Comparisons were made between diversity
      discovered amongst a panel of Ae. tauschii accessions, bread wheat varieties and
      lines from the CIMMYT synthetic hexaploid wheat programme. The selection of Ae.
      tauschii accessions based on differing approaches had significant effect on
      diversity within each set. Our results suggest that a strategy that combines
      several criteria will be most effective in maximising the sampled variation
      across multiple parameters. The analysis of multiple layers of variation in ex
      situ Ae. tauschii collections allows for an informed and rational approach to the
      inclusion of wild relatives into crop breeding programmes. 

PMID- 23558984
TI  - Read all about it! Why TBI is big news.

PMID- 23558986
TI  - Change in antipsychotic usage pattern and risk of relapse in older patients with
      schizophrenia.
AB  - OBJECTIVE: The aim of this study was to explore the use of first (FGAs) and
      second generation antipsychotics (SGAs) in older outpatients with schizophrenia
      and schizoaffective disorder. Factors associated with schizophrenic relapses were
      also studied. METHODS: The study sample consisting of 8792 patients aged 64 years
      or more was collected from Finnish nationwide registers. The register data on the
      use of FGAs and SGAs were followed up between 1998 and 2003. Factors associated
      with psychiatric hospitalization in 1999 indicating relapse were studied using
      logistic regression analysis. RESULTS: The use of SGAs increased from 2.8% to
      12.4%, and the use of FGAs decreased from 57.5% to 39.4%. The use of a
      combination of SGAs and FGAs increased from 4.0% to 8.5%. The proportion of those
      who did not buy any antipsychotics varied between 35.8% and 39.7%. The number of
      patients hospitalized on psychiatric wards within a year (1999; relapsed) was
      8.8%. Factors independently associated with relapse were use of combined FGAs and
      SGAs [odds ratio (OR) 1.70, p = 0.001] and use of antidepressants (OR 1.27, p =
      0.019). Diagnosis of cardiovascular disease was negatively associated with risk
      of schizophrenic relapse (OR 0.84, p = 0.040). CONCLUSION: The use of SGAs
      increased while the use of FGAs decreased in older outpatients with
      schizophrenia. Almost 40% of the study sample did not use any antipsychotic
      medication. The 1-year relapse rate was 8.8%. Several factors, such as combined
      use of FGAs and SGAs, or antidepressants, were associated with schizophrenic
      relapse, whereas cardiovascular disease showed a negative association with the
      relapse.

PMID- 23558987
TI  - A light- and electron microscopic study of primordial germ cells in the zebra
      fish (Danio rerio).
AB  - In sexually reproducing organisms, primordial germ cells (PGCs) give rise to the
      cells of the germ line, the gametes. In many animals, PGCs are set apart from
      somatic cells early during embryogenesis. This study explores the origin of
      primordial germ cells (PGCs) of the zebra fish and examines their morphology
      during early development (1st day-15th day). PGCs were selectively stained by the
      alkaline phosphatase histochemical reaction and viewed by light and electron
      microscopy from the time they are first detectable in the yolk sac endoderm. PGCs
      occurred in the subendodermal space on the syncytial periblast; differing from
      the surrounding endodermal cells. Later the PGCs moved to between the blastoderm
      and yolk sac and transferred to the dorsal mesentery where they formed gonadal
      anlage with mesoderm cells. PGCs were easily distinguished from somatic cells by
      their morphology and low electron density of their nuclei. Under light
      microscopy, PCGs were rounded with a distinct cytoplasmic membrane.

PMID- 23558985
TI  - Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers.
AB  - Over the past decade, public awareness of the long-term pathological consequences
      of traumatic brain injury (TBI) has increased. Such awareness has been stimulated
      mainly by reports of progressive neurological dysfunction in athletes exposed to
      repetitive concussions in high-impact sports such as boxing and American
      football, and by the rising number of TBIs in war veterans who are now more
      likely to survive explosive blasts owing to improved treatment. Moreover, the
      entity of chronic traumatic encephalopathy (CTE)--which is marked by prominent
      neuropsychiatric features including dementia, parkinsonism, depression,
      agitation, psychosis, and aggression--has become increasingly recognized as a
      potential late outcome of repetitive TBI. Annually, about 1% of the population in
      developed countries experiences a clinically relevant TBI. The goal of this
      Review is to provide an overview of the latest understanding of CTE
      pathophysiology, and to delineate the key issues that are challenging clinical
      and research communities, such as accurate quantification of the risk of CTE, and
      development of reliable biomarkers for single-incident TBI and CTE.

PMID- 23558988
TI  - Malnutrition affects the pressor response to microinjection of L-glutamate into
      the RVLM of awake rats.
AB  - Post-weaning protein malnutrition is often related to the development of
      cardiovascular and metabolic diseases in humans, as well to changed content of
      neurotransmitters in the central nervous system under experimental conditions.
      The rostral ventrolateral medulla (RVLM) is a bulbar region that contains
      sympathetic premotor neurons; the excitatory amino acid L-glutamate seems to be
      the main neurotransmitter at this level. The aim of the present study was to
      evaluate the possible change in the L-glutamate sensitivity of the RVLM neurons
      of malnourished animals. Male Fischer rats were divided into two groups: control
      (n = 15) and malnourished (n = 19). Four days before the experiments, guide
      cannulas were implanted bilaterally in direction of the RVLM for microinjection
      of L-glutamate. Twenty-four hours before the experiments, the femoral artery was
      cannulated for cardiovascular recordings. The results showed that the baseline
      heart rate increased in malnourished compared to control animals (412.18 +/-
      16.03 bpm vs. 370.74 +/- 9.59 bpm, respectively). Malnourished animals presented
      a dissimilar concentration-dependent pressor response curve to L-glutamate and an
      attenuated baroreflex gain. Our results suggest that post-weaning protein
      restriction affects glutamatergic neurotransmission of the baroreflex at the RVLM
      level.

PMID- 23558989
TI  - Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats.
AB  - Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl
      coenzyme A reductase and have a major place in the treatment of atherosclerotic
      disease. Recent studies have shown anti-inflammatory properties of statins. The
      purpose of this study was to evaluate the anti-inflammatory effect of simvastatin
      on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female
      Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT)
      phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP
      PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT
      BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was
      administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of
      simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN
      gamma, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue
      hydroxyproline (HPL) content and by histopathological examination (Ashcroft
      score). BLM caused significant change in BAL fluid cytokine levels and increased
      both HPL content and histopathological score (p<0.001 for all). While LD
      simvastatin had no effect on cytokine levels, HD significantly reduced IL-13
      (15.12 +/-7.08 pg/ml vs. 4.43+/-2.34 pg/mL; p<0.05) and TGF-beta1 levels (269.25
      +/-65.42 pg/mL vs. 131.75+/-32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin
      attenuated HPL content or Ashcroft score. In conclusion, this study showed that
      LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the
      high dose caused partial improvement in profibrotic cytokine levels.

PMID- 23558990
TI  - IGF2 expression in blood is not associated with its imprinting status in healthy
      pregnant Chinese women.
AB  - Loss of Imprinting (LOI) of IGF2 and over-expressed IGF2 are associated with
      tumorigenesis. Our previous epidemiological study found a relatively high
      frequency of IGF2 LOI in healthy mid-gestation pregnant women. The aim of this
      study is to determine whether the expression of IGF2 is associated with its
      imprinting status in healthy Chinese pregnant women. The IGF2 imprinting status
      of 300 pregnant women was analyzed. 20 cases of IGF2 LOI and 20 cases of IGF2
      retention of imprinting (ROI) were selected randomly for IGF2 expression
      analysis. The expression pattern of IGF2 between the group with IGF2 ROI and
      group with IGF2 LOI in healthy Chinese pregnant women was evaluated by real time
      PCR and western blot. The result showed no significant differences between IGF2
      ROI and LOI groups in mRNA and protein levels. These results imply that IGF2
      imprinting status has no obvious impact on its expression. There may be some
      unknown important factors other than imprinting status driving IGF2 expression.

PMID- 23558991
TI  - Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo.
AB  - Hypoxia-ischemia (HI) occurring in immature brains stimulates the expression of
      tissue-type plasminogen activator (tPA). Neuroserpin is a selected inhibitor of
      tPA in the central nerves system. However, the role that neuroserpin plays and
      the possible mechanisms involved during neonatal HI are poorly defined. In this
      study, an oxygen-glucose deprivation and reoxygenation (OGD/R) model was
      generated with cultured rat cortical neurons mimicking neonatal HI injury ex
      vivo, and an acute neuronal excitatory injury was induced by exposure to a high
      concentration of N-methyl-D-aspartic acid (NMDA). Cells received either
      neuroserpin or MK-801, an antagonist of the NMDA receptor, during OGD/R, and were
      incubated with or without neuroserpin after NMDA exposure. Cell viability and
      morphology were detected by a Cell Counting Kit-8 and immunohistochemical
      staining, respectively. TPA expression and activity were also assessed. We found
      that MK-801 alleviated injuries induced by OGD/R, suggesting an excitatory damage
      involvement. Neuroserpin provided a dose-dependent neuroprotective effect in both
      OGD/R and acute excitatory injuries by inhibiting the activity of tPA, without
      affecting neuronal tPA expression. Neuroserpin protected neurons against OGD/R
      even after a delayed administration of 3h. Collectively, our data indicate that
      neuroserpin protects neurons against OGD/R. mainly by inhibiting tPA-mediated
      acute neuronal excitotoxicity.

PMID- 23558992
TI  - Assessment of allelopathic properties of Aloe ferox Mill. on turnip, beetroot and
      carrot.
AB  - Turnip (Brassica rapa var. rapa L.), beetroot (Beta vulgaris L.) and carrot
      (Daucus carota L.) are common vegetables in South Africa. The allelopathic
      potential of aqueous leaf and root extracts of Aloe ferox Mill.- a highly valued
      medicinal plant- was evaluated against seed germination and seedling growth of
      the three vegetables in Petri dish experiments. The extracts were tested at
      concentrations of 2, 4, 6, 8, and 10 mg/mL. Leaf extract concentrations above 4
      mg/mL inhibited the germination of all the crops, while the root extract had no
      significant effect on germination irrespective of concentration. Interestingly,
      the lowest concentration of leaf extract stimulated root length elongation of
      beetroot by 31.71%. Other concentrations significantly inhibited both root and
      shoot growth of the vegetable crops except the turnip shoot. The most sensitive
      crop was carrot, with percentage inhibition ranging from 29.15 to 100% for root
      and shoot lengths. Lower percentage inhibition was observed for the root extract
      than the leaf extract against shoot growth of beetroot and carrot. The results
      from this study suggested the presence of allelochemicals mostly in the leaves of
      A. ferox that could inhibit the growth of the turnip, beetroot and carrot.

PMID- 23558993
TI  - lnterleukin-8 gene polymorphism and susceptibility to gastric cancer in a
      Brazilian population.
AB  - BACKGROUND: Studies have demonstrated that some polymorphisms in different
      interleukin genes may increase the risk of cancer. The aim of this study was to
      investigate the association between the IL-8 (rs4073) -251A/T gene polymorphism
      and the risk of gastric cancer (GC). PATIENTS AND METHODS: A case-control study
      was conducted on patients with noncardia gastric cancer. DNA was extracted from
      leukocytes and the IL-8 (rs4073) -251A/T polymorphism was analyzed by PCR-RFLP.
      Infection with Helicobacter pylori was investigated in the serum by ELISA.
      RESULTS: The sample consisted of 104 patients with GC and 196 controls. Cigarette
      smoking (P=0.007) and high fat intake (P=0.01) were more frequent in patients
      with GC. The proportion of patients infected with H. pylori was similar in the
      two groups (P=0.101). The frequency of the genotype A/T was higher in the cancer
      group (P=0.008). An increased risk of GC was found in subjects carrying the
      genotype A/T (OR=2.50, CI: 1.27-4.90), subjects with high fat intake (OR=1.92,
      CI: 1.17-3.15), and smokers (OR=2.00, CI: 1.203.31). CONCLUSIONS: Subjects with
      the heterozygous A/T genotype, high fat intake and smokers or ex-smokers
      presented an increased risk of GC. Individuals with A/A genotype may have
      protective effect for GC.

PMID- 23558994
TI  - Biological screening of selected flora of Pakistan.
AB  - Methanolic extracts of different parts of five medicinal plants, Ferula
      assafoetidaL. resin, Grewia asiaticaL. leaves, Ipomoea hederaceaJacq. seeds,
      Lepidium sativumL. seeds and Terminalia chebulaRetz. fruits were tested in
      vitrofor their cytotoxic, phytotoxic, insecticidal, nematicidal and anthelmintic
      activities. Ipomoea hederaceashowed very significant phytotoxic and cytotoxic
      activity, with 100% inhibition of Lemna minorgrowth and 100% death of Artemia
      salinaat concentrations of 1000 and 100 ug mL-1. Grewia asiaticaexhibited very
      weak activities while Lepidium sativumand Ferula assafoetidashowed moderate to
      good potential in all three bioassays. The results suggest screening of Ipomoea
      hederaceaseeds further for isolation of bioactive compounds that may be
      responsible for its toxic potential.

PMID- 23558995
TI  - Age-related changes in quality and fertility of porcine semen.
AB  - The aim of this study was to investigate the effect of boar age on quality traits
      and fertility of liquid-stored semen. Boars were allocated into 3 age groups: 7
      10 months (young), 18-33 months (mature), 51-61 months (old). Ejaculates of >
      200x10(6) sperm/ml and 85% total motile sperm were extended to 30x10(6) sperm/ml,
      stored at 17-18  degrees C and used within 12-24 h for artificial insemination
      (AI) of 2062 multiparous sows. After 24 h of storage, aliquots of diluted semen
      were assessed for sperm progressive motility (SPM), incidence of sperm chromatin
      instability (SCI), proportion of live morphologically normal sperm (LMNS) and
      head morphometry of LMNS. The results showed that young boars had higher
      percentages of SCI and lower proportions of LMNS than those of the mature (p <
      0.05) and old (p < 0.001) boars, respectively. Sperm head dimensions of young and
      old boars were greater (p < 0.03-0.001) than those of mature boars. The farrowing
      rate of young boars (65%) was significantly lower (p < 0.001; chi2= 30-61) than
      those of the mature (87.2%) and old (84.7%) boars. The relationship between sperm
      head dimensions and boar fertility was non-significant. In conclusion, boar age
      is an important physiological factor contributing to the success of swine AI.

PMID- 23558997
TI  - Sporogenesis and development of gametophytes in an endangered plant, Tetracentron
      sinense Oliv.
AB  - The sporogenesis and development of gametophytes in Tetracentron sinense Oliv.
      were studied with light microscopy. The anther has four microsporangia; its
      primary anther wall consists of an epidermis, an endothecium, one or two middle
      layers and one glandular tapetum. Simultaneous cytokinesis follows meiosis,
      forming a tetrahedral tetrad. Mature pollen grains are two-celled at the time of
      anther dehiscence. Its ovule is anatropous, bitegmic and crassinucellate; the
      development of the female gametophyte is of the monosporic 8-nucleate Polygonum
      type. Significantly, some striking features were first found in T. sinense: (1)
      anther dehiscence occurs soon after the endothecium fibrously thickens and the
      intersporangial septum degenerates; (2) tapetum degeneration is retarded,
      persisting up to the stage of two-celled pollen grain; (3) a few cellular events
      such as the vacuolization and the contraction and deformation of the pollen
      mother cell (PMC) and microspore are not normal at the PMC, dyad and tetrad
      stages. The abnormalities during male reproduction might be one of important
      factors resulting in the poor natural regeneration of T. sinense.

PMID- 23558996
TI  - Antioxidant, antibacterial activity and brine shrimp toxicity test of some
      mountainous lichens from Nepal.
AB  - A total of twenty four lichen species belonging to six families were collected
      from mountainous region of Nepal. The methanol extracts of each species were
      tested for antimicrobial and antioxidant activities in vitro. It was found that
      extracts of twenty one lichen species were active against B. subtilis and seven
      species were active against S. aureus. Similarly, in DPPH assay, three species
      Peltigera sp.,Cladonia sp., and Canoparmelia sp. showed comparable activity with
      commercial standard, BHA. In ABTS+ assay, extracts of Parmoterma sp., Ramalina
      sp., Peltigera sp. and Cladonia sp. showed stronger activity than ascorbic acid.
      The observed data after comparison with previously published reports indicated
      that the high altitude lichens contain stronger antioxidant and antibacterial
      constituents. Similarly, the methanol extracts of Heterodermia sp. and Ramalina
      sp. showed comparable toxicity effect with commercial standard berberine chloride
      indicating a potent source of anticancer drugs.

PMID- 23558998
TI  - Leishmanicidal activity of carvacrol-rich essential oil from Lippia sidoides
      Cham.
AB  - Leishamaniasis is a disease that affects more than 2 million people worldwide,
      whose causative agent is Leishmania spp. The current therapy for leishmaniasis is
      far from satisfactory. All available drugs, including pentavalent antimony,
      require parenteral administration and are potentially toxic. Moreover, an
      increase in clinical resistance to these drugs has been reported. In this
      scenario, plant essential oils used traditionally in folk medicine are emerging
      as alternative sources for chemotherapeutic compounds. In this study, in vitro
      leishmanicidal effects of a thymol- and a carvacrol-rich essential oil from
      leaves of Lippia sidoides Cham. were investigated. The essential oils were
      extracted and their constituents were characterized by gas chromatography coupled
      to mass spectrometry (GC/MS). Both essential oils showed significant activity
      against promastigote forms of Leishmania chagasi. However, we found that
      carvacrol-rich essential oil was more effective, with IC50/72 h of 54.8 MUg/mL
      compared to 74.1 MUg/mL for thymol-rich oil. Carvacrol also showed lower IC50
      than thymol. Our data suggest that L. sidoides essential oils are indeed
      promising sources of leishmanicidal compounds.

PMID- 23558999
TI  - Gastrodia elata Blume and its pure compounds protect BV-2 microglial-derived cell
      lines against beta-amyloid: the involvement of GRP78 and CHOP.
AB  - OBJECTIVES: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known
      for its therapeutic benefits against neurodegenerative diseases. Microglial
      activation and death have been implicated in the pathogenesis of a variety of
      neurodegenerative diseases, including Alzheimer's disease. In this study, GE and
      its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied
      to beta-amyloid-induced BV2 mouse microglial cells. MATERIALS AND METHODS: Cell
      viability was assessed by the MTT assay and Western blotting was also performed.
      RESULTS: beta-amyloid-induced cell death was shown to be induced time- and dose
      dependently. To examine the cell death mechanism, we confirmed the involvement of
      ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress
      protein, was expressed at high levels but glucose-regulated protein 78 (GRP78),
      an anti-apoptotic ER stress protein with chaperone activity, was only slightly
      affected by treatment with beta-amyloid. However, pretreatment with GE and its
      components inhibited the expression of CHOP but increased that of GRP78 in beta
      amyloid-treated cells. This study also showed that a single treatment with GE
      extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for
      enhanced protein folding machinery, suggesting a protective mechanism for GE
      against beta-amyloid. CONCLUSIONS: This study reveals the protective effects of
      GE against beta-amyloid-induced cell death, possibly through the enhancement of
      protein folding machinery of a representative protein, GRP78, and the regulation
      of CHOP in BV2 mouse microglial cells.

PMID- 23559000
TI  - Weighted registration of 123I-FP-CIT SPECT images improves accuracy of binding
      potential estimates in pathologically low striatal uptake.
AB  - To test whether the use of a striatum weighted image may improve registration
      accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS),
      weighted images were generated by increasing signal intensity of striatal voxels
      and used as intermediate dataset for co-registering the brain image onto
      template. Experimental validation was performed using an anthropomorphic striatal
      phantom. (123)I-FP-CIT SPECT binding ratios were manually determined in 67 PS
      subjects and compared to those obtained using unsupervised standard (UWR) and
      weighted registered (WR) approach. Normalized cost function was used to evaluate
      the accuracy of phantom and subjects registered images to the template.
      Reproducibility between unsupervised and manual ratios was assessed by using
      intra-class correlation coefficient (ICC) and Bland and Altman analysis.
      Correlation coefficient was used to assess the dependence of semi-quantitative
      ratios on clinical findings. Weighted method improves accuracy of brain
      registration onto template as determined by cost function in phantom (0.86 +/-
      0.06 vs. 0.98 +/- 0.02; Student's t-test, P = 0.04) and in subject scans (0.69 +/
      0.06 vs. 0.53 +/- 0.06; Student's t-test, P < 0.0001). Agreement between manual
      and unsupervised derived binding ratios as measured by ICC was significantly
      higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was
      significantly correlated with manual and unsupervised derived binding potential.
      In phantom, as well as in subjects studies, correlations were more significant
      using the WR method (BPm: R(2) = 0.36, P = 0.0001; BPwr: R(2) = 0.368, P =
      0.0001; BPuwr: R(2) = 0.300, P = 0.0008). Weighted registration improves accuracy
      of binding potential estimates and may be a promising approach to enhance the
      diagnostic outcome of SPECT imaging, correlation with disease severity, and for
      monitoring disease progression in Parkinsonian syndromes.

PMID- 23559001
TI  - Suppression of SHP-1 promotes corticospinal tract sprouting and functional
      recovery after brain injury.
AB  - Reorganization of spared neural network connections is one of the most important
      processes for restoring impaired function after brain injury. However, plasticity
      is quite limited in the adult brain due to the presence of inhibitory molecules
      and a lack of intrinsic neuronal signals for axonal growth. Src homology 2
      containing phosphatase (SHP)-1 has been shown to have a role in axon growth
      inhibition. Here, we tested the hypothesis that SHP-1 negatively affects axonal
      reorganization. We observed that unilateral motor cortex injury led to increased
      expression and activity of SHP-1 in the contralesional cortex. In this model,
      corticospinal axons originating from the contralesional cortex sprouted into the
      denervated side of the cervical spinal cord after injury. We observed that the
      number of sprouting fibers was increased in SHP-1-deficient heterozygous viable
      motheaten (+/me(v)) mice, which show reduced SHP-1 activity, and in wild-type
      mice treated with an SHP inhibitor. Motor function recovery of impaired forelimb
      was enhanced in +/me(v) mice. Collectively, our results indicate that
      downregulation of SHP-1 activity promotes corticospinal tract sprouting and
      functional recovery after brain injury.

PMID- 23559002
TI  - Deciphering the signaling networks underlying simvastatin-induced apoptosis in
      human cancer cells: evidence for non-canonical activation of RhoA and Rac1
      GTPases.
AB  - Although statins are known to inhibit proliferation and induce death in a number
      of cancer cell types, the mechanisms through which downregulation of the
      mevalonate (MVA) pathway activates death signaling remain poorly understood. Here
      we set out to unravel the signaling networks downstream of the MVA pathway that
      mediate the death-inducing activity of simvastatin. Consistent with previous
      reports, exogenously added geranylgeranylpyrophosphate, but not
      farnesylpyrophosphate, prevented simvastatin's growth-inhibitory effect, thereby
      suggesting the involvement of geranylgeranylated proteins such as Rho GTPases in
      the anticancer activity of simvastatin. Indeed, simvastatin treatment led to
      increased levels of unprenylated Ras homolog gene family, member A (RhoA), Ras
      related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42).
      Intriguingly, instead of inhibiting the functions of Rho GTPases as was expected
      with loss of prenylation, simvastatin caused a paradoxical increase in the GTP
      bound forms of RhoA, Rac1 and Cdc42. Furthermore, simvastatin disrupted the
      binding of Rho GTPases with the cytosolic inhibitor Rho GDIalpha, which provides
      a potential mechanism for GTP loading of the cytosolic Rho GTPases. We also show
      that the unprenylated RhoA- and Rac1-GTP retained at least part of their
      functional activities, as evidenced by the increase in intracellular superoxide
      production and JNK activation in response to simvastatin. Notably, blocking
      superoxide production attenuated JNK activation as well as cell death induced by
      simvastatin. Finally, we provide evidence for the involvement of the B-cell
      lymphoma protein 2 family, Bcl-2-interacting mediator (Bim), in a JNK-dependent
      manner, in the apoptosis-inducing activity of simvastatin. Taken together, our
      data highlight the critical role of non-canonical regulation of Rho GTPases and
      involvement of downstream superoxide-mediated activation of JNK pathway in the
      anticancer activity of simvastatin, which would have potential clinical
      implications.

PMID- 23559004
TI  - Zebularine regulates early stages of mESC differentiation: effect on cardiac
      commitment.
AB  - Lineage commitment during embryonic stem cell (ESC) differentiation is controlled
      not only by a gamut of transcription factors but also by epigenetic events,
      mainly histone deacetylation and promoter DNA methylation. The DNA demethylation
      agent 5'-aza-2'-deoxycytidine (AzadC) has been widely described as an effective
      promoter of cardiomyogenic differentiation in various stem cell types. However,
      its toxicity and instability complicate its use. Therefore, the purpose of this
      study was to examine the effects of zebularine (1-(beta-D-ribofuranosyl)-1,2
      dihydropyrimidin-2-1), a stable and non-toxic DNA cytosine methylation inhibitor,
      on mouse ESC (mESC) differentiation. Herein, we report that treating embryoid
      bodies, generated from mESCs, with 30 MUM zebularine for 7 days led to greater
      cell differentiation and induced the expression of several cardiac-specific
      markers that were detected using reverse transcription-polymerase chain reaction
      (RT-PCR), real-time PCR, immunostaining and flow cytometry. Zebularine enhanced
      the expression of cardiac markers and the appearance of beating cells that
      responded to cardiac drugs, including ion channel blockers (diltiazem) and beta
      adrenergic stimulators (isoproterenol). Gene promoter methylation status was
      assessed using methylation-specific PCR (MSP) and validated by bisulfite
      sequencing analysis. Global gene expression profiling using microarrays showed
      that zebularine-differentiated cells are distinct from control ESCs. Pathway
      analysis revealed an enhancement of cellular processes such as embryonic
      development, cardiovascular system development and function. In addition, the
      whole-cell proteins exhibited different profiles as analyzed by two-dimensional
      differential-in-gel-electrophoresis. Our results indicate that zebularine
      regulates mesodermal differentiation of mESCs, controls promoter methylation of
      crucial cardiac genes and may help to improve cardiomyogenic differentiation.

PMID- 23559003
TI  - Inhibition of 12/15-lipoxygenase by baicalein induces microglia PPARbeta/delta: a
      potential therapeutic role for CNS autoimmune disease.
AB  - 12/15-Lipoxygenase (12/15-LO) is an enzyme that converts polyunsaturated fatty
      acids into bioactive lipid derivatives. In this study, we showed that inhibition
      of 12/15-LO by baicalein (BA) significantly attenuated clinical severity of
      experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis (MS). Inhibited migration of autoimmune T cells into the central
      nervous system (CNS) by BA treatment could be attributed to reduced activation of
      microglia, which was indicated by suppressed phagocytosis, and decreased
      production of proinflammatory cytokines and chemokines in the CNS. We further
      observed that inhibition of 12/15-LO with BA led to increased expression of
      peroxisome proliferator-activated receptor (PPAR)beta/delta in microglia of EAE
      mice. This was confirmed in vitro in primary microglia and a microglia cell line,
      BV2. In addition, we demonstrated that BA did not affect 12/15-LO or 5
      lipoxygenase (5-LO) expression in microglia, but significantly decreased 12/15-LO
      products without influencing the levels of 5-LO metabolites. Moreover, among
      these compounds only 12/15-LO metabolite 12-hydroxyeicosatetraenoic acid was able
      to reverse BA-mediated upregulation of PPARbeta/delta in BV2 cells. We also
      showed that inhibition of microglia activation by PPARbeta/delta was associated
      with repressed NF-kappaB and MAPK activities. Our findings indicate that
      inhibition of 12/15-LO induces PPARbeta/delta, demonstrating important regulatory
      properties of 12/15-LO in CNS inflammation. This reveals potential therapeutic
      applications for MS.

PMID- 23559005
TI  - AF-MSCs fate can be regulated by culture conditions.
AB  - Human mesenchymal stem cells (hMSCs) represent a population of multipotent
      adherent cells able to differentiate into many lineages. In our previous studies,
      we isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF) and
      characterized them based on their phenotype, pluripotency and proteomic profile.
      In the present study, we investigated the plasticity of these cells based on
      their differentiation, dedifferentiation and transdifferentiation potential in
      vitro. To this end, adipocyte-like cells (AL cells) derived from AF-MSCs can
      regain, under certain culture conditions, a more primitive phenotype through the
      process of dedifferentiation. Dedifferentiated AL cells derived from AF-MSCs (DAF
      MSCs), gradually lost the expression of adipogenic markers and obtained similar
      morphology and differentiation potential to AF-MSCs, together with regaining the
      pluripotency marker expression. Moreover, a comparative proteomic analysis of AF
      MSCs, AL cells and DAF-MSCs revealed 31 differentially expressed proteins among
      the three cell populations. Proteins, such as vimentin, galectin-1 and prohibitin
      that have a significant role in stem cell regulatory mechanisms, were expressed
      in higher levels in AF-MSCs and DAF-MSCs compared with AL cells. We next
      investigated whether AL cells could transdifferentiate into hepatocyte-like cells
      (HL cells) directly or through a dedifferentiation step. AL cells were cultured
      in hepatogenic medium and 4 days later they obtained a phenotype similar to AF
      MSCs, and were termed as transdifferentiated AF-MSCs (TRAF-MSCs). This finding,
      together with the increase in pluripotency marker expression, indicated the
      adaption of a more primitive phenotype before transdifferentiation. Additionally,
      we observed that AF-, DAF- and TRAF-MSCs displayed similar clonogenic potential,
      secretome and proteome profile. Considering the easy access to this fetal cell
      source, the plasticity of AF-MSCs and their potential to dedifferentiate and
      transdifferentiate, AF may provide a valuable tool for cell therapy and tissue
      engineering applications.

PMID- 23559006
TI  - GSK-3beta signaling determines autophagy activation in the breast tumor cell line
      MCF7 and inclusion formation in the non-tumor cell line MCF10A in response to
      proteasome inhibition.
AB  - The ubiquitin-proteasome system and the autophagy-lysosome pathway are the two
      main mechanisms for eukaryotic intracellular protein degradation. Proteasome
      inhibitors are used for the treatment of some types of cancer, whereas autophagy
      seems to have a dual role in tumor cell survival and death. However, the
      relationship between both pathways has not been extensively studied in tumor
      cells. We have investigated both proteolytic systems in the human epithelial
      breast non-tumor cell line MCF10A and in the human epithelial breast tumor cell
      line MCF7. In basal condition, tumor cells showed a lower proteasome function but
      a higher autophagy activity when compared with MCF10A cells. Importantly,
      proteasome inhibition (PI) leads to different responses in both cell types. Tumor
      cells showed a dose-dependent glycogen synthase kinase-3 (GSK-3)beta inhibition,
      a huge increase in the expression of the transcription factor CHOP and an active
      processing of caspase-8. By contrast, MCF10A cells fully activated GSK-3beta and
      showed a lower expression of both CHOP and processed caspase-8. These molecular
      differences were reflected in a dose-dependent autophagy activation and cell
      death in tumor cells, while non-tumor cells exhibited the formation of inclusion
      bodies and a decrease in the cell death rate. Importantly, the behavior of the
      MCF7 cells can be reproduced in MCF10A cells when GSK-3beta and the proteasome
      were simultaneously inhibited. Under this situation, MCF10A cells strongly
      activated autophagy, showing minimal inclusion bodies, increased CHOP expression
      and cell death rate. These findings support GSK-3beta signaling as a key
      mechanism in regulating autophagy activation or inclusion formation in human
      tumor or non-tumor breast cells, respectively, which may shed new light on breast
      cancer control.

PMID- 23559007
TI  - Trolox contributes to Nrf2-mediated protection of human and murine primary
      alveolar type II cells from injury by cigarette smoke.
AB  - Cigarette smoke (CS) is a main risk factor for chronic obstructive pulmonary
      disease (COPD). Oxidative stress induced by CS causes DNA and lung damage.
      Oxidant/antioxidant imbalance occurs in the distal air spaces of smokers and in
      patients with COPD. We studied the effect of oxidative stress generated by CS
      both in vivo and in vitro on murine primary alveolar type II (ATII) cells
      isolated from nuclear erythroid 2-related factor-2 (Nrf2)(-/-) mice. We
      determined human primary ATII cell injury by CS in vitro and analyzed ATII cells
      isolated from smoker and non-smoker lung donors ex vivo. We also studied whether
      trolox (water-soluble derivative of vitamin E) could protect murine and human
      ATII cells against CS-induced DNA damage and/or decrease injury. We analyzed
      oxidative stress by 4-hydroxynonenal expression, reactive oxygen species (ROS)
      generation by Amplex Red Hydrogen Peroxide Assay, Nrf2, heme oxygenase 1, p53 and
      P53-binding protein 1 (53BP1) expression by immonoblotting, Nrf2 nuclear
      translocation, Nrf2 and p53 DNA-binding activities, apoptosis by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and cytokine
      production by ELISA. We found that ATII cells isolated from Nrf2(-/-) mice are
      more susceptible to CS-induced oxidative DNA damage mediated by p53/53BP1 both in
      vivo and in vitro compared with wild-type mice. Therefore, Nrf2 activation is a
      key factor to protect ATII cells against injury by CS. Moreover, trolox abolished
      human ATII cell injury and decreased DNA damage induced by CS in vitro.
      Furthermore, we found higher inflammation and p53 mRNA expression by RT-PCR in
      ATII cells isolated from smoker lung donors in comparison with non-smokers ex
      vivo. Our results indicate that the Nrf2 and p53 cross talk in ATII cells affect
      the susceptibility of these cells to injury by CS. Trolox can protect against
      oxidative stress, genotoxicity and inflammation induced by CS through ROS
      scavenging mechanism, and serve as a potential antioxidant prevention strategy
      against oxidative injury of ATII cells in CS-related lung diseases.

PMID- 23559008
TI  - TTC5 is required to prevent apoptosis of acute myeloid leukemia stem cells.
AB  - Using a screening strategy, we identified the tetratricopeptide repeat (TPR)
      motif protein, Tetratricopeptide repeat domain 5 (TTC5, also known as stress
      responsive activator of p300 or Strap) as required for the survival of human
      acute myeloid leukemia (AML) cells. TTC5 is a stress-inducible transcription
      cofactor known to interact directly with the histone acetyltransferase EP300 to
      augment the TP53 response. Knockdown (KD) of TTC5 induced apoptosis of both
      murine and human AML cells, with concomitant loss of clonogenic and leukemia
      initiating potential; KD of EP300 elicited a similar phenotype. Consistent with
      the physical interaction of TTC5 and EP300, the onset of apoptosis following KD
      of either gene was preceded by reduced expression of BCL2 and increased
      expression of pro-apoptotic genes. Forced expression of BCL2 blocked apoptosis
      and partially rescued the clonogenic potential of AML cells following TTC5 KD. KD
      of both genes also led to the accumulation of MYC, an acetylation target of
      EP300, and the form of MYC that accumulated exhibited relative hypoacetylation at
      K148 and K157, residues targeted by EP300. In view of the ability of excess
      cellular MYC to sensitize cells to apoptosis, our data suggest a model whereby
      TTC5 and EP300 cooperate to prevent excessive accumulation of MYC in AML cells
      and their sensitization to cell death. They further reveal a hitherto
      unappreciated role for TTC5 in leukemic hematopoiesis.

PMID- 23559009
TI  - Mutant p53-R273H gains new function in sustained activation of EGFR signaling via
      suppressing miR-27a expression.
AB  - p53 is a major tumor suppressor whose function is pivotal for protection against
      cancer. In over half of human cancers, p53 is inactivated due to either point
      mutation or loss of p53 gene. It has been well established that in addition to
      abrogating the tumor-suppressive function of wild-type p53, mutant p53 gains new
      functions and actively contributes to various stages of tumor progression.
      However, little is known about whether microRNA (miRNA) is involved in the gain
      of-function of mutant p53. Here we report miR-27a as a novel downstream
      transcriptional target of mutant p53-273H. Mutant p53 binds to the miR-27a
      promoter region and suppresses its expression. We also identify epidermal growth
      factor receptor (EGFR) as a direct target of miR-27a. Via the miR-27a/EGFR axis,
      mutant p53-273H promotes a sustained EGF-induced extracellular signal-regulated
      kinase 1/2 activation, thereby facilitating cell proliferation and tumorigenesis.
      Collectively, this work reveals a direct link between the gain-of-function of
      mutant p53 and miRNA and uncovers a novel mutant p53-273H/miR-27a/EGFR pathway
      that has an important role in promoting tumor development.

PMID- 23559010
TI  - PTPL1 and PKCdelta contribute to proapoptotic signalling in prostate cancer
      cells.
AB  - PTPL1 is a non-receptor protein tyrosine phosphatase involved in apoptosis
      regulation, although controversial findings have been reported in different
      cancer types. We report here a proapoptotic role for PTPL1 in PC3 and LNCaP
      prostate cancer cells, as its absence induces apoptosis resistance upon treatment
      with different drugs. In PC3 cells, PTPL1 silencing by small interfering RNA
      influences the expression levels of Bcl-xL and Mcl-1(S) proteins as well as final
      events in the apoptotic process such as activation of caspases and caspase
      mediated cleavage of proteins like Mcl-1 or poly (ADP-ribose) polymerase. We have
      identified PKCdelta as an intermediary of PTPL1-mediated apoptotic signalling and
      that phosphorylation status of NF-kappaB and IkappaBalpha is influenced by PTPL1
      and PKCdelta. Furthermore, the loss of PTPL1 and PKCdelta expression in poorly
      differentiated, more aggressive human prostate cancers also indicate that their
      absence could be related to apoptosis resistance and tumour progression.

PMID- 23559011
TI  - Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin
      mediated degradation of cellular FLIP(long) in human colon cancer cells.
AB  - Colorectal cancer is the third leading cause of cancer-related mortality in the
      world; the main cause of death of colorectal cancer is hepatic metastases, which
      can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this
      study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c
      FLIP(L)), a major regulator of the death receptor (DR) pathway of apoptosis,
      thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated
      mitochondria-independent apoptosis. We observed that overexpression of c-FLIP(L)
      in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas
      silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia
      altered c-FLIP(L) protein stability without concomitant reductions in FLIP mRNA.
      Ubiquitination of c-FLIP(L) was increased by hyperthermia, and proteasome
      inhibitor MG132 prevented heat-induced downregulation of c-FLIP(L). These results
      suggest the involvement of the ubiquitin-proteasome system in this process. We
      also found lysine residue 195 (K195) to be essential for c-FLIP(L) ubiquitination
      and proteolysis, as mutant c-FLIP(L) lysine 195 arginine (arginine replacing
      lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia
      triggered degradation, and thus partially blocked the synergistic effect of Mapa
      and hyperthermia. Our observations reveal that hyperthermia transiently reduced c
      FLIP(L) by proteolysis linked to K195 ubiquitination, which contributed to the
      synergistic effect between Mapa and hyperthermia. This study supports the
      application of hyperthermia combined with other regimens to treat colorectal
      hepatic metastases.

PMID- 23559012
TI  - FK506 binding protein 51 positively regulates melanoma stemness and metastatic
      potential.
AB  - Melanoma is the most aggressive skin cancer; there is no cure in advanced stages.
      Identifying molecular participants in melanoma progression may provide useful
      diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an
      immunophilin with a relevant role in developmental stages, is highly expressed in
      melanoma and correlates with aggressiveness and therapy resistance. We
      hypothesized a role for FKBP51 in melanoma invasive behaviour. FKBP51 promoted
      activation of epithelial-to-mesenchymal transition (EMT) genes and improved
      melanoma cell migration and invasion. In addition, FKBP51 induced some melanoma
      stem cell (MCSC) genes. Purified MCSCs expressed high EMT genes levels,
      suggesting that genetic programs of EMT and MCSCs overlap. Immunohistochemistry
      of samples from patients showed intense FKBP51 nuclear signal and cytoplasmic
      positivity for the stem cell marker nestin in extravasating melanoma cells and
      metastatic brains. In addition, FKBP51 targeting by small interfering RNA (siRNA)
      prevented the massive metastatic substitution of liver and lung in a mouse model
      of experimental metastasis. The present study provides evidence that the genetic
      programs of cancer stemness and invasiveness overlap in melanoma, and that FKBP51
      plays a pivotal role in sustaining such a program.

PMID- 23559013
TI  - A DR6/p75(NTR) complex is responsible for beta-amyloid-induced cortical neuron
      death.
AB  - The p75 neurotrophin receptor (p75(NTR)) is a known mediator of beta-amyloid
      (Abeta)-induced neurotoxicity implicated in Alzheimer's disease (AD). Here, we
      demonstrate that death receptor 6 (DR6) binds to p75(NTR) and is a component of
      the p75(NTR) signaling complex responsible for Abeta-induced cortical neuron
      death. Cortical neurons isolated from either DR6 or p75(NTR) null mice are
      resistant to Abeta-induced neurotoxicity. Blocking DR6 function in cortical
      neurons by anti-DR6 antibodies that block the binding of DR6 to p75(NTR) receptor
      complex or by a dominant negative DR6 construct lacking the cytoplasmic signaling
      death domain attenuates Abeta-induced caspase 3 activation and cell death. DR6
      expression is upregulated in AD cortex and correlates with elevated neuronal
      death. Targeting the disruption of the DR6/p75(NTR) complex to prevent Abeta
      cytotoxicity represents a new approach for the treatment of neurodegenerative
      disorders such as AD.

PMID- 23559015
TI  - Reticulon1-C modulates protein disulphide isomerase function.
AB  - Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of
      secreted and membrane-bound proteins. Accumulation of unfolded and misfolded
      proteins in ER underlies a wide range of human neurodegenerative disorders.
      Hence, molecules regulating the ER stress response represent potential candidates
      as drug targets for tackling these diseases. Protein disulphide isomerase (PDI)
      is a chaperone involved in ER stress pathway, its activity being an important
      cellular defense against protein misfolding. Here, we demonstrate that human
      neuroblastoma SH-SY5Y cells overexpressing the reticulon protein 1-C (RTN1-C)
      reticulon family member show a PDI punctuate subcellular distribution identified
      as ER vesicles. This represents an event associated with a significant increase
      of PDI enzymatic activity. We provide evidence that the modulation of PDI
      localization and activity does not only rely upon ER stress induction or
      upregulation of its synthesis, but tightly correlates to an alteration in its
      nitrosylation status. By using different RTN1-C mutants, we demonstrate that the
      observed effects depend on RTN1-C N-terminal region and on the integrity of the
      microtubule network. Overall, our results indicate that RTN1-C induces PDI
      redistribution in ER vesicles, and concomitantly modulates its activity by
      decreasing the levels of its S-nitrosylated form. Thus RTN1-C represents a
      promising candidate to modulate PDI function.

PMID- 23559014
TI  - Phosphoinositide 3-kinase couples NMDA receptors to superoxide release in
      excitotoxic neuronal death.
AB  - Sustained activation of neuronal N-methly D-aspartate (NMDA)-type glutamate
      receptors leads to excitotoxic cell death in stroke, trauma, and
      neurodegenerative disorders. Excitotoxic neuronal death results in part from
      superoxide produced by neuronal NADPH oxidase (NOX2), but how NMDA receptors are
      coupled to neuronal NOX2 activation is not well understood. Here, we identify a
      signaling pathway coupling NMDA receptor activation to NOX2 activation in primary
      neuron cultures. Calcium influx through the NR2B subunit of NMDA receptors leads
      to the activation of phosphoinositide 3-kinase (PI3K). Formation of
      phosphatidylinositol (3,4,5)-triphosphate (PI(3,4,5)P3) by PI3K activates the
      atypical protein kinase C, PKC zeta (PKCzeta), which in turn phosphorylates the
      p47(phox) organizing subunit of neuronal NOX2. Calcium influx through NR2B
      containing NMDA receptors triggered mitochondrial depolarization, NOX2
      activation, superoxide formation, and cell death. However, equivalent magnitude
      calcium elevations induced by ionomycin did not induce NOX2 activation or
      neuronal death, despite causing mitochondrial depolarization. The PI3K inhibitor
      wortmannin prevented NMDA-induced NOX2 activation and cell death, without
      preventing cell swelling, calcium elevation, or mitochondrial depolarization. The
      effects of wortmannin were circumvented by exogenous supply of the PI3K product,
      PI(3,4,5)P3, and by transfection with protein kinase M, a constitutively active
      form of PKCzeta. These findings demonstrate that superoxide formation and
      excitotoxic neuronal death can be dissociated from mitochondrial depolarization,
      and identify a novel role for PI3K in this cell death pathway. Perturbations in
      this pathway may either increase or decrease superoxide production in response to
      NMDA receptor activation, and may thereby impact neurological disorders, in which
      excitotoxicity is a contributing factor.

PMID- 23559016
TI  - Role of alpha-crystallin B as a regulatory switch in modulating cardiomyocyte
      apoptosis by mitochondria or endoplasmic reticulum during cardiac hypertrophy and
      myocardial infarction.
AB  - Cardiac hypertrophy and myocardial infarction (MI) are two major causes of heart
      failure with different etiologies. However, the molecular mechanisms associated
      with these two diseases are not yet fully understood. So, this study was designed
      to decipher the process of cardiomyocyte apoptosis during cardiac hypertrophy and
      MI in vivo. Our study revealed that mitochondrial outer membrane channel protein
      voltage-dependent anion channel-1 (VDAC1) was upregulated exclusively during
      cardiac hypertrophy, whereas 78 kDa glucose-regulated protein (GRP78) was
      exclusively upregulated during MI, which is an important upstream regulator of
      the endoplasmic reticulum (ER) stress pathway. Further downstream analysis
      revealed that mitochondrial pathway of apoptosis is instrumental in case of
      hypertrophy, whereas ER stress-induced apoptosis is predominant during MI, which
      was confirmed by treatment with either siRNA against VDAC1 or ER stress inhibitor
      tauroursodeoxycholic acid (TUDCA). Very interestingly, our data also showed that
      the expression and interaction of small heat-shock protein alpha-crystallin B
      (CRYAB) with VDAC1 was much more pronounced during MI compared with either
      hypertrophy or control. The study demonstrated for the first time that two
      different organelles--mitochondria and ER have predominant roles in mediating
      cardiomyocyte death signaling during hypertrophy and MI, respectively, and
      activation of CRYAB acts as a molecular switch in bypassing mitochondrial pathway
      of apoptosis during MI.

PMID- 23559017
TI  - The effect of a LYSE exporter overexpression on L-arginine production in
      Corynebacterium crenatum.
AB  - Corynebacterium crenatum SYPA is an aerobic and industrial L-arginine producer. A
      lysE deletion mutant was constructed searching a natural function of this in C.
      crenatum SYPA. Tracking determination of intracellular and extracellular L
      arginine in the minimum culture CGXII showed that LysE did play an important role
      in transporting L-arginine from intracellular to extracellular, without which the
      accumulation of intracellular L-arginine of C. crenatum SYPA could reach an
      extremely high concentration. Nevertheless, the lower intracellular concentration
      of L-arginine could decrease the feedback inhibition in the biosynthesis of L
      arginine. To improve the yield from excretion, we attempted to achieve
      overexpress in the L-arginine transporter in C. crenatum SYPA. Thus, the
      heterologous and homologous expressions of EcargO and CclysE, respectively, were
      carried out by means of the shuttle plasmid pJCtac in C. crenatum SYPA. It was
      found that L-arginine production was improved by 13.6 % because of the
      overexpression of lysE in the strain (SYPA/pJCE) contrast to the wild-type strain
      and reached 35.9 g/L, whereas L-arginine production of the strain SYPA/pJCO was
      scarcely changed. Consequently, we succeeded in obtaining a mutant form of LysE
      which has an effect to decrease the intracellular concentration of L-arginine in
      an L-arginine producer of C. crenatum SYPA and found that the production of L
      arginine by C. crenatum carrying lysE was improved. These results show the
      importance of the factor (lysE) involved in the excretion of L-arginine on its
      over-production in C. crenatum. 

PMID- 23559018
TI  - What we call what we do affects how we do it: a new nomenclature for simulation
      research in medical education.
AB  - Rapid technological advances and concern for patient safety have increased the
      focus on simulation as a pedagogical tool for educating health care providers. To
      date, simulation research scholarship has focused on two areas; evaluating
      instructional designs of simulation programs, and the integration of simulation
      into a broader educational context. However, these two categories of research
      currently exist under a single label-Simulation-Based Medical Education. In this
      paper we argue that introducing a more refined nomenclature within which to frame
      simulation research is necessary for researchers, to appropriately design
      research studies and describe their findings, and for end-point users (such as
      program directors and educators), to more appropriately understand and utilize
      this evidence.

PMID- 23559019
TI  - The future of biomedical research.

PMID- 23559020
TI  - EEG markers for characterizing anomalous activities of cerebral neurons in NAT
      (neuronal activity topography) method.
AB  - A pair of markers, sNAT and vNAT, is derived from the electroencephalogram (EEG)
      power spectra (PS) recorded for 5 min with 21 electrodes (4-20 Hz) arranged
      according to the 10-20 standard. These markers form a new diagnosis tool "NAT"
      aiming at characterizing various brain disorders. Each signal sequence is divided
      into segments of 0.64 s and its discrete PS consists of eleven frequency
      components from 4.68 (3 * 1.56) Hz through 20.34 (13 * 1.56) Hz. PS is normalized
      to its mean and the bias of PS components on each frequency component across the
      21 signal channels is reset to zero. The marker sNAT consists of ten frequency
      components on 21 channels, characterizing neuronal hyperactivity or hypoactivity
      as compared with NLc (normal controls). The marker vNAT consists of ten ratios
      between adjacent PS components denoting the over- or undersynchrony of collective
      neuronal activities as compared with NLc. The likelihood of a test subject to a
      specified brain disease is defined in terms of the normalized distance to the
      template NAT state of the disease in the NAT space. Separation of MCI-AD patients
      (developing AD in 12-18 months) from NLc is made with a false alarm rate of 15%.
      Locations with neuronal hypoactivity and undersynchrony of AD patients agree with
      locations of rCBF reduction measured by SPECT. The 2-D diagram composed of the
      binary likelihoods between ADc and NLc in the two representations of sNAT and
      vNAT enables tracing the NAT state of a test subject approaching the AD area, and
      the follow-up of the treatment effects.

PMID- 23559021
TI  - Topology and random-walk network representation of cardiac dynamics for
      localization of myocardial infarction.
AB  - While detection of acute cardiac disorders such as myocardial infarction (MI)
      from electrocardiogram (ECG) and vectorcardiogram (VCG) has been widely reported,
      identification of MI locations from these signals, pivotal for timely therapeutic
      and prognostic interventions, remains a standing issue. We present an approach
      for MI localization based on representing complex spatiotemporal patterns of
      cardiac dynamics as a random-walk network reconstructed from the evolution of VCG
      signals across a 3-D state space. Extensive tests with signals from the PTB
      database of the PhysioNet databank suggest that locations of MI can be determined
      accurately (sensitivity of ~88% and specificity of ~92%) from tracking certain
      consistently estimated invariants of this random-walk representation. 

PMID- 23559022
TI  - Analysis of the spatial sensitivity of conductance/admittance catheter
      ventricular volume estimation.
AB  - Conductance catheters are known to have a nonuniform spatial sensitivity due to
      the distribution of the electric field. The Geselowitz relation is applied to
      murine and multisegment conductance catheters using finite element models to
      determine the spatial sensitivity in a uniform medium and simplified left
      ventricle models. A new formulation is proposed that allows determination of the
      spatial sensitivity to admittance. Analysis of FEM numerical modeling results
      using the Geselowitz relation provides a true measure of parallel conductance in
      simplified left ventricle models for assessment of the admittance method and
      hypertonic saline techniques. The spatial sensitivity of blood conductance (Gb)
      is determined throughout the cardiac cycle. Gb is converted to volume using Wei's
      equation to determine if the presence of myocardium alters the nonlinear
      relationship through changes to the electric field. Results show that muscle
      conductance (Gm) from the admittance method matches results from the Geselowitz
      relation and that the relationship between Gb and volume is accurately fit using
      Wei's equation. Single-segment admittance measurements in large animals result in
      a more evenly distributed sensitivity to the LV blood pool. The hypertonic saline
      method overestimates parallel conductance throughout the cardiac cycle in both
      murine and multisegment conductance catheters. 

PMID- 23559024
TI  - Real-time lumped parameter modeling of cardiovascular dynamics using
      electrocardiogram signals: toward virtual cardiovascular instruments.
AB  - We present an approach to deriving a real-time, lumped parameter cardiovascular
      dynamics model that uses features extracted from online electrocardiogram (ECG)
      signal recordings to generate certain surrogate hemodynamic signals. The model
      represents the coupled dynamics of the heart chambers, valves, and pulmonary and
      systemic blood circulation loops in the form of nonlinear differential equations.
      The features extracted from ECG signals were used to estimate the timings and
      amplitudes of the atrioventricular activation input functions as well as other
      model parameters that capture the effect of cardiac morphological and
      physiological characteristics. The model was tested using hemodynamic signals
      from the PhysioNet MGH/MF Waveform database. The results suggest that the model
      can capture the salient time and frequency patterns of the measured central
      venous pressure, pulmonary arterial pressure, and respiratory impedance signals
      (R(2) > 0.65). We have developed a method based on Anderson-Darling statistic and
      Kullback-Leibler divergence to compare the clinical measures (i.e., systolic and
      diastolic pressures) estimated from model waveform-extrema with those from actual
      measurements. The test statistics of the model waveform-extrema were
      statistically indistinguishable from the measured values with beat-to-beat
      rejection rates of 10%. The results indicate the potential of a virtual
      instrument that uses the model-derived signals for clinical diagnosis in lieu of
      expensive instrumentation. 

PMID- 23559023
TI  - Electroanatomical characterization of atrial microfibrosis in a histologically
      detailed computer model.
AB  - Fibrosis is thought to play an important role in the formation and maintenance of
      atrial fibrillation (AF). The propensity of fibrosis to increase AF vulnerability
      depends not only on its amount, its texture plays a crucial role as well. While
      the detection of fibrotic tissue patches in the atria with extracellular
      recordings is feasible based on the analysis of electrogram fractionation, as
      used in clinical practice to identify ablation targets, the classification of
      fibrotic texture is a more challenging problem. This study seeks to establish a
      method for the electroanatomical characterization of the fibrotic textures based
      on the analysis of electrogram fractionation. The proposed method exploits the
      dependence of fractionation patterns on the incidence direction of wavefronts
      which differs significantly as a function of texture. A histologically detailed
      computer model of the right atrial isthmus was developed for testing the method.
      A stimulation protocol was conceived which generated various incidence directions
      for any given recording site where electrograms were computed. A classification
      method is derived then for discriminating three types of fibrosis, no fibrosis
      (control), diffuse, and patchy fibrosis. Simulation results showed that
      electrogram fractionation and amplitudes and their dependence upon incidence
      direction allow a robust discrimination between different classes of fibrosis.
      Finally, to minimize the technical effort, sensitivity analysis was performed to
      identify a minimum number of incidence directions required for robust
      classification. 

PMID- 23559025
TI  - Simultaneous localization of lumbar vertebrae and intervertebral discs with SVM
      based MRF.
AB  - This paper presents a method for localizing and labeling the lumbar vertebrae and
      intervertebral discs in mid-sagittal MR image slices. The approach is based on a
      Markov-chain-like graphical model of the ordered discs and vertebrae in the
      lumbar spine. The graphical model is formulated by combining local image features
      and semiglobal geometrical information. The local image features are extracted
      from the image by employing pyramidal histogram of oriented gradients (PHOG) and
      a novel descriptor that we call image projection descriptor (IPD). These features
      are trained with support vector machines (SVM) and each pixel in the target image
      is locally assigned a score. These local scores are combined with the semiglobal
      geometrical information like the distance ratio and angle between the neighboring
      structures under the Markov random field (MRF) framework. An exact localization
      of discs and vertebrae is inferred from the MRF by finding a maximum a posteriori
      solution efficiently using dynamic programming. As a result of the novel features
      introduced, our system can scale-invariantly localize discs and vertebra at the
      same time even in the existence of missing structures. The proposed system is
      tested and validated on a clinical lumbar spine MR image dataset containing 80
      subjects of which 64 have disc- and vertebra-related diseases and abnormalities.
      The experiments show that our system is successful even in abnormal cases and our
      results are comparable to the state of the art. 

PMID- 23559027
TI  - Challenges of today: at one side employment important for quality of life and to
      avoid depression; at the other side a worldwide economic crisis.

PMID- 23559026
TI  - The treatment of adolescents and young adults with acute lymphoblastic leukemia.
AB  - Adolescents and young adult (AYA) patients with acute lymphoblastic leukemia
      (ALL), 16-40 years of age, were historically not the focus of prospective studies
      on ALL treatment. This population has unique genetic, immunophenotypic, and
      clinical features, differing from both pediatric and older adult patients, with
      outcomes somewhere between these two populations. However, it has been suggested
      that outcomes (event-free and overall survival) for these patients are better
      when they are treated with pediatric-inspired therapeutic regimens. This has been
      attributed to increased dose and frequency of non-myelosuppressive therapy,
      earlier and more frequent central nervous system prophylaxis, and longer
      maintenance therapy. However, management by the treating oncologist and adherence
      by the patients are equally vital. Ultimately, the combination of improved
      treatment regimens and organizational management are required to improve outcomes
      of ALL in the AYA population.

PMID- 23559028
TI  - The influence of depression on physical complications in spinal cord injury:
      behavioral mechanisms and health-care implications.
AB  - STUDY DESIGN: This study is a literature review and a proposed conceptual model.
      OBJECTIVES: The objective of this study is to develop a conceptual model to
      explore the relationship between the presence of depressive symptoms and
      secondary physical complications such as pressure ulcers, urinary tract
      infections and autonomic dysreflexia in spinal cord injury (SCI). SETTING:
      Community setting for individuals with SCI. METHODS: A conceptual model
      explaining the mechanism underlying the relationship between depression and
      secondary physical SCI complications was developed based on the International
      Classification of Functioning, Disability and Health (ICF). A literature review
      was conducted to develop the model and to identify potential mechanisms
      responsible for the association. RESULTS: A conceptual model based on ICF was
      created, informed by the literature discussing the link between depression and
      secondary physical SCI complications. Evidence in the literature was located that
      supports both a causal connection between depression and increased physical
      complications and/or the potential mechanisms mediating that connection.
      CONCLUSION: The proposed model can be utilized to encourage further research on
      the influence of depression on SCI outcomes and the importance of prompt and
      effective identification and treatment of depressive symptoms. Additional
      research is needed to assess the relationship between depression and secondary
      physical SCI complications, and to test the validity of the model.

PMID- 23559029
TI  - Effect of positive end-expiratory pressure on regional ventilation distribution
      during mechanical ventilation after surfactant depletion.
AB  - BACKGROUND: Ventilator-induced lung injury occurs due to exaggerated local
      stresses, repeated collapse, and opening of terminal air spaces in poorly aerated
      dependent lung, and increased stretch in nondependent lung. The aim of this study
      was to quantify the functional behavior of peripheral lung units in whole-lung
      lavage-induced surfactant depletion, and to assess the effect of positive end
      expiratory pressure. METHODS: The authors used synchrotron imaging to measure
      lung aeration and regional specific ventilation at positive end-expiratory
      pressure of 3 and 9 cm H2O, before and after whole-lung lavage in rabbits.
      Respiratory mechanical parameters were measured, and helium-washout was used to
      assess end-expiratory lung volume. RESULTS: Atelectatic, poorly, normally
      aerated, hyperinflated, and trapped regions could be identified using the imaging
      technique used in this study. Surfactant depletion significantly increased
      atelectasis (6.3+/-3.3 [mean+/-SEM]% total lung area; P=0.04 vs. control) and
      poor aeration in dependent lung. Regional ventilation was distributed to poorly
      aerated regions with high (16.4+/-4.4%; P<0.001), normal (20.7+/-5.9%; P<0.001
      vs. control), and low (5.7+/-1.2%; P<0.05 vs. control) specific ventilation.
      Significant redistribution of ventilation to normally aerated nondependent lung
      regions occurred (41.0+/-9.6%; P=0.03 vs. control). Increasing positive end
      expiratory pressure level to 9 cm H2O significantly reduced poor aeration and
      recruited atelectasis, but ventilation redistribution persisted (39.2+/-9.5%;
      P<0.001 vs. control). CONCLUSIONS: Ventilation of poorly aerated dependent lung
      regions, which can promote the local concentration of mechanical stresses, was
      the predominant functional behavior in surfactant-depleted lung. Potential tidal
      recruitment of atelectatic lung regions involved a smaller fraction of the imaged
      lung. Significant ventilation redistribution to aerated lung regions places these
      at risk of increased stretch injury.

PMID- 23559030
TI  - In vivo fluorescence-mediated tomography imaging demonstrates atorvastatin
      mediated reduction of lesion macrophages in ApoE-/- mice.
AB  - BACKGROUND: Macrophage recruitment into atherosclerotic plaques drives lesion
      progression, destabilization, and rupture. Chronic statin treatment reduces
      macrophage plaque content. Information on dynamics of macrophage recruitment
      would help assessing plaque vulnerability and guiding therapy. Techniques to
      image macrophage homing to vulnerable plaques in vivo are scarcely available. The
      authors tested if noninvasive fluorescence-mediated tomography (FMT) can assess
      plaque-stabilizing effects of short-term high-dosage atorvastatin. METHODS:
      Macrophages from green-fluorescent-protein-transgenic mice were labeled with a
      near-infrared fluorescent dye and were injected IV in apolipoprotein E-deficient
      mice (n=9) on Western diet 7 days after guidewire-injury of the carotid artery.
      FMT-scans, 2 and 7 days thereafter, quantified macrophage recruitment into
      carotid artery plaques. Atorvastatin was tested for macrophage adhesion,
      proliferation, and viability (n=5 to 6) in vitro. Fourteen mice received
      atorvastatin or vehicle for 4 days after 16 weeks on Western diet. FMT assessed
      macrophage recruitment into aortic and innominate artery lesions. Means (+/-SD)%
      are reported. RESULTS: Double-labeled macrophages were recruited into carotid
      artery lesions. FMT resolved fluorescence projecting on the injured carotid
      artery and detected a signal increase to 300% (+/-191) after guidewire injury.
      Atorvastatin reduced macrophage adhesion to activated endothelial cells by 36%
      (+/-19). In a clinically relevant proof-of-concept intervention, FMT-imaging
      detected that 4 days atorvastatin treatment reduced macrophage recruitment by 57%
      (+/-8) indicating plaque stabilization. Immunohistochemistry confirmed reduced
      macrophage infiltration. CONCLUSIONS: FMT optical imaging proved its high
      potential for clinical applicability for tracking recruitment of near-infrared
      fluorescent-labeled macrophages to vulnerable plaques in vivo. FMT-based
      quantification of macrophage recruitment demonstrated rapid plaque stabilization
      by 4-day atorvastatin treatment in apolipoprotein E-deficient mice.

PMID- 23559031
TI  - Learning from a master.

PMID- 23559032
TI  - Highly undersampled magnetic resonance image reconstruction using two-level
      Bregman method with dictionary updating.
AB  - In recent years Bregman iterative method (or related augmented Lagrangian method)
      has shown to be an efficient optimization technique for various inverse problems.
      In this paper, we propose a two-level Bregman Method with dictionary updating for
      highly undersampled magnetic resonance (MR) image reconstruction. The outer-level
      Bregman iterative procedure enforces the sampled k-space data constraints, while
      the inner-level Bregman method devotes to updating dictionary and sparse
      representation of small overlapping image patches, emphasizing local structure
      adaptively. Modified sparse coding stage and simple dictionary updating stage
      applied in the inner minimization make the whole algorithm converge in a
      relatively small number of iterations, and enable accurate MR image
      reconstruction from highly undersampled k-space data. Experimental results on
      both simulated MR images and real MR data consistently demonstrate that the
      proposed algorithm can efficiently reconstruct MR images and present advantages
      over the current state-of-the-art reconstruction approach. 

PMID- 23559033
TI  - High resolution ultrasound in posterior interosseous nerve syndrome.
AB  - INTRODUCTION: Posterior interosseous nerve (PIN) syndrome is a rare compression
      neuropathy of the PIN in the region of the supinator muscle, most common by the
      arcade of Frohse. We aimed to specify ultrasonographic findings in patients with
      PIN syndrome in comparison to healthy volunteers. METHODS: Ultrasound images and
      clinical data of 13 patients with PIN syndrome confirmed by neurological
      examination and electrophysiological testing were evaluated retrospectively.
      Anteroposterior nerve diameters measured at the arcade of Frohse were compared
      with those of 20 healthy volunteers. The echotexture and the presence of a
      caliber change of the PIN were additionally assessed. RESULTS: Enlargement of the
      PIN was seen in all patients with PIN syndrome, but not in volunteers
      (statistically significant difference in mean diameter P < 0.05). Furthermore,
      edema and caliber change of the PIN were present in all patients. CONCLUSIONS:
      High-resolution ultrasound allows for differentiation between patients with PIN
      syndrome and healthy volunteers.

PMID- 23559034
TI  - A review of cell assemblies.
AB  - Since the cell assembly (CA) was hypothesised, it has gained substantial support
      and is believed to be the neural basis of psychological concepts. A CA is a
      relatively small set of connected neurons, that through neural firing can sustain
      activation without stimulus from outside the CA, and is formed by learning.
      Extensive evidence from multiple single unit recording and other techniques
      provides support for the existence of CAs that have these properties, and that
      their neurons also spike with some degree of synchrony. Since the evidence is so
      broad and deep, the review concludes that CAs are all but certain. A model of CAs
      is introduced that is informal, but is broad enough to include, e.g. synfire
      chains, without including, e.g. holographic reduced representation. CAs are found
      in most cortical areas and in some sub-cortical areas, they are involved in
      psychological tasks including categorisation, short-term memory and long-term
      memory, and are central to other tasks including working memory. There is
      currently insufficient evidence to conclude that CAs are the neural basis of all
      concepts. A range of models have been used to simulate CA behaviour including
      associative memory and more process- oriented tasks such as natural language
      parsing. Questions involving CAs, e.g. memory persistence, CAs' complex
      interactions with brain waves and learning, remain unanswered. CA research
      involves a wide range of disciplines including biology and psychology, and this
      paper reviews literature directly related to the CA, providing a basis of
      discussion for this interdisciplinary community on this important topic.
      Hopefully, this discussion will lead to more formal and accurate models of CAs
      that are better linked to neuropsychological data.

PMID- 23559035
TI  - Proline/arginine-rich end leucine-rich repeat protein N-terminus is a novel
      osteoclast antagonist that counteracts bone loss.
AB  - (hbd) PRELP is a peptide corresponding to the N-terminal heparin binding domain
      of the matrix protein proline/arginine-rich end leucine-rich repeat protein
      (PRELP). (hbd) PRELP inhibits osteoclastogenesis entering pre-fusion osteoclasts
      through a chondroitin sulfate- and annexin 2-dependent mechanism and reducing the
      nuclear factor-kappaB transcription factor activity. In this work, we
      hypothesized that (hbd) PRELP could have a pharmacological relevance,
      counteracting bone loss in a variety of in vivo models of bone diseases induced
      by exacerbated osteoclast activity. In healthy mice, we demonstrated that the
      peptide targeted the bone and increased trabecular bone mass over basal level. In
      mice treated with retinoic acid to induce an acute increase of osteoclast
      formation, the peptide consistently antagonized osteoclastogenesis and prevented
      the increase of the serum levels of the osteoclast-specific marker tartrate
      resistant acid phosphatase. In ovariectomized mice, in which osteoclast activity
      was chronically enhanced by estrogen deficiency, (hbd) PRELP counteracted
      exacerbated osteoclast activity and bone loss. In mice carrying osteolytic bone
      metastases, in which osteoclastogenesis and bone resorption were enhanced by
      tumor cell-derived factors, (hbd) PRELP reduced the incidence of osteolytic
      lesions, both preventively and curatively, with mechanisms involving impaired
      tumor cell homing to bone and tumor growth in the bone microenvironment.
      Interestingly, in tumor-bearing mice, (hbd) PRELP also inhibited breast tumor
      growth in orthotopic sites and development of metastatic disease in visceral
      organs, reducing cachexia and improving survival especially when administered
      preventively. (hbd) PRELP was retained in the tumor tissue and appeared to affect
      tumor growth by interacting with the microenvironment rather than by directly
      affecting the tumor cells. Because safety studies and high-dose treatments
      revealed no adverse effects, (hbd) PRELP could be employed as a novel biological
      agent to combat experimentally induced bone loss and breast cancer metastases,
      with a potential translational impact. 

PMID- 23559037
TI  - "Role magnets"? An empirical investigation of popularity trajectories for life
      course persistent individuals during adolescence.
AB  - Recent scholarship has focused on the role of social status in peer groups to
      explain the fact that delinquency is disproportionately committed during
      adolescence. Yet, the precise mechanism linking adolescence, social status, and
      antisocial behavior is not well understood. Dual-taxonomy postulates a testable
      mechanism that links the sudden increase in risky behavior among adolescents to
      the social magnetism of a small group of persistently antisocial individuals,
      referred to here as the "role magnet" hypothesis. Using semi-parametric group
      based trajectory modeling and growth-curve modeling, this study provides the
      first test of this hypothesis by examining physical violence and popularity
      trajectories for 1,845 male respondents age 11-32 from a nationally
      representative sample (54 % non-Hispanic White; 21 % non-Hispanic African
      American; 17 % Hispanic; 8 % Asian). Individuals assigned to a "chronic violence"
      trajectory group showed consistently lower average levels of popularity from 11
      to 19. But, these same individuals experienced increases in popularity during
      early adolescence and subsequent declines in late adolescence. These findings are
      linked to current research examining social status as a mechanism generating
      antisocial behavior during adolescence and the consequences of delayed entry into
      adult roles. 

PMID- 23559038
TI  - Molecular detection of human metapneumovirus and human bocavirus on oropharyngeal
      swabs collected from young children with acute respiratory tract infections from
      rural and peri-urban communities in South India.
AB  - BACKGROUND: Acute respiratory tract infections (ARTIs) are one of the major
      causes of morbidity and mortality among young children in developing countries.
      Information on the incidence of human metapneumovirus (hMPV) and human bocavirus
      (HBoV) infections in developing countries, especially among rural children, is
      very limited. OBJECTIVES: This study was conducted to identify whether these
      viruses were associated with ARTI among children <=5 years of age in rural and
      peri-urban populations in South India. METHODS: The study was cross-sectional
      with prospective sample collection. Oropharyngeal swabs were collected from
      children <=5 years of age presenting with ARTI. None of the children in this
      study were known to have any immunosuppressive conditions. The two viruses, hMPV
      and HBoV, were identified using semi-nested polymerase chain reaction (PCR)
      assays and one-step PCR assays, respectively. The lower limits of detection of
      hMPV and HBoV were 6.69 * 10(5) plasmid copies and 5.77 * 10(3) plasmid copies,
      respectively, per 5 MUL PCR reaction input. RESULTS: The frequency of hMPV
      infection in children was higher than that of HBoV infection. The different
      frequencies of hMPV in patients in various age groups with upper and lower
      respiratory tract infections were compared, and the variance was found to be
      insignificant. In the 38 children who were hMPV positive, the majority (73.7%)
      were from rural communities. The overall hMPV-positive rate was higher in the
      rural population than in the peri-urban population, but the difference was
      statistically insignificant. The youngest age at which hMPV-positive status was
      recorded was 5 months. CONCLUSION: This study demonstrated that hMPV was
      associated with a significant number (i.e. >10%) of ARTIs in children in South
      India, whereas a relatively smaller number of HBoV infections was observed.

PMID- 23559039
TI  - Analysis of sequence diversity of human metapneumovirus collected from young
      children with acute respiratory tract infections in South India.
AB  - BACKGROUND: Human metapneumovirus (hMPV), which has a global distribution, is an
      important cause of acute respiratory tract infections, especially in children and
      immunocompromised patients. METHODS: We investigated the genetic variability of
      partial nucleoprotein (N) gene sequences of hMPV strains identified among young
      children in South India. The sequences of the N gene were compared with
      previously reported sequences available in the GenBank repository. RESULTS: The
      results showed that strains are localized in a geographically circumscribed area
      (topotype). The results also demonstrates that viruses from the same genetic
      lineage can circulate concurrently within a given location during a given season.
      The close clustering of the majority of our hMPV isolates indicates that the N
      gene sequences in the virus population are relatively homogeneous, and suggests
      temporal rather than geographic variations in the evolutionary pattern. In our
      study, the majority of the strains belonged to genetic lineage B2 (71.1 %),
      followed by A2b (18.4 %), A2a (7.9 %), and B1 (2.6 %), demonstrating the presence
      of 4 of the 5 known genotypes of hMPV. Global alignment of the nucleotide
      sequences showed that the strains are closely related to sequences from Canada,
      The Netherlands, and Australasia. Differences at the nucleotide level and the
      amino acid level were identified. The results provide evidence for the diversity
      of the N gene of hMPV in samples collected from South India compared with global
      strains. When investigated for selective pressure, the sequences showed 1
      positively selected site and 19 negatively selected sites. CONCLUSION: These data
      should prove useful in further investigations of the evolutionary dynamics of
      hMPV infection.

PMID- 23559040
TI  - Quadriceps muscle strength and its relationship to radiographic knee
      osteoarthritis in Japanese elderly.
AB  - BACKGROUND: Knee osteoarthritis (OA) is a multifactorial disease and strongly
      affected by mechanical factors. The aims of the present study were to assess
      validity and reliability of a new muscle strength measuring device, the
      Quadriceps Training Machine (QTM) and evaluate the relationship between
      quadriceps strength measured by QTM and radiographic knee OA by epidemiological
      survey. METHODS: The isometric knee extension muscle strength of QTM was compared
      with BIODEX in 24 healthy adults. Then, the relationship between radiographic
      knee OA and quadriceps strength using QTM was investigated with 2,032 knees in
      1,016 subjects by an epidemiological survey (Matsudai Knee Osteoarthritis
      Survey). RESULTS: Significant correlation was observed between QTM and BIODEX (r
      = 0.69, 0.82). In the Matsudai Knee Osteoarthritis Survey, the prevalence of
      radiographic OA (grade II or higher upon Kellgren-Lawrence classification) was:
      13, 36.9, 67.8, and 86.5 %, regarding women in their fifties, sixties, seventies,
      and eighties, respectively, and was 1.7, 13.4, 33.5, and 66.2 % regarding men,
      respectively. Quadriceps muscle strength declined following 50 years of age, and
      significant decline was observed in the their sixties and seventies. Quadriceps
      muscle strength of the OA group (grades II, III and IV) was significantly
      declined compared with that of the Non-OA group (grade-0 and I). Furthermore, the
      tendency of the muscle strength level to decline with the progression of knee OA
      grade was particularly observed between grade 0 and grade I in both men and women
      and between grade I and grade II in men. CONCLUSION: The relationship between
      radiographic knee OA and quadriceps strength was quantitatively evaluated by an
      epidemiological survey, and we found a correlation between knee OA and the
      decline in quadriceps strength. Furthermore, it was suggested that the decline in
      quadriceps muscle strength may be more strongly related to the incidence of knee
      OA than to its progression.

PMID- 23559041
TI  - The bacteria and bacteriophages from a Mesquite Flats site of the Death Valley
      desert.
AB  - Arid zones cover over 30 % of the Earth's continental surface. In order to better
      understand the role of microbes in this type of harsh environment, we isolated
      and characterized the bacteriophages from samples of the surface sand of the
      Mesquite Flats region via electron microscopy and DNA sequencing of a select
      number of cloned phage DNAs. An electron microscopic analysis of the recovered
      virus-like particles revealed at least 11 apparently different morphotypes
      sharing structural characteristics of the Caudoviridae family of tailed phages.
      We found that 36 % of the sequences contained no significant identity (e-value
      >10(-3)) with sequences in the databases. Pilot sequencing of cloned 16S rRNA
      genes identified Bacteroidetes and Proteobacteria as the major bacterial groups
      present in this severe environment. The majority of the 16S rDNA sequences from
      the total (uncultured) bacterial population displayed <=96 % identity to 16S rRNA
      genes in the database, suggesting an unexplored bacterial population likely
      adapted to a desert environment. In addition, we also isolated and identified 38
      cultivable bacterial strains, the majority of which belonged to the genus
      Bacillus. Mitomycin-C treatment of the cultivable bacteria demonstrated that the
      vast majority (84 %) contained at least one SOS-inducible prophage.

PMID- 23559042
TI  - Penicillium subrubescens, a new species efficiently producing inulinase.
AB  - Inulin is a reserve carbohydrate in about 15 % of the flowering plants and is
      accumulated in underground tubers of e.g. chicory, dahlia and Jerusalem
      artichoke. This carbohydrate consists of linear chains of beta-(2,1)-linked
      fructose attached to a sucrose molecule. Inulinases hydrolyse inulin into
      fructose and glucose. To find efficient inulin degrading fungi, 126 fungal
      strains from the Fungal Biotechnology Culture Collection (FBCC) at University of
      Helsinki and 74 freshly isolated strains from soil around Jerusalem artichoke
      tubers were screened in liquid cultures with inulin as a sole source of carbon or
      ground Jerusalem artichoke tubers, which contains up to 19 % (fresh weight)
      inulin. Inulinase and invertase activities were assayed by the dinitrosalicylic
      acid (DNS) method and a freshly isolated Penicillium strain originating from
      agricultural soil (FBCC 1632) was the most efficient inulinase producer. When it
      was cultivated at pH 6 and 28  degrees C in 2 litre bioreactors using inulin and
      Jerusalem artichoke as a carbon source, inulinase and invertase activities were
      on day 4 7.7 and 3.1 U mL(-1), respectively. The released sugars analysed by TLC
      and HPLC showed that considerable amounts of fructose were released while the
      levels of oligofructans were low, indicating an exoinulinase type of activity.
      Taxonomic study of the inulinase producing strain showed that this isolate
      represents a new species belonging in Penicillium section Lanata-divaricata. This
      new species produces a unique combination of extrolites and is phenotypically and
      phylogenetically closely related to Penicillium pulvillorum. We propose the name
      Penicillium subrubescens sp. nov. (CBS 132785(T) = FBCC 1632(T)) for this new
      species.

PMID- 23559044
TI  - Editor's Note.

PMID- 23559045
TI  - The inventory of botanical curiosities in Pierre-Francois-Xavier de Charlevoix's
      Nouvelle France (1744).
AB  - The article explores the botanical contributions of Pierre-Francois-Xavier de
      Charlevoix's book Histoire et description generale de la Nouvelle France vis-a
      vis the contributions of previous researchers, his use of iconographic and
      discursive representations and its relevance to the project of French
      colonization. It investigates why he refused Linnaeus' taxonomic model and what
      he intended with his catalogue of botanical curiosities. The unfolding of his
      philosophical and religious trajectory allows to understand his stance regarding
      the classification of nature, the meanings of ethnological information, his forms
      of intellectual appropriation, and his use of discourse and botanical iconography
      as political and emotional propaganda to encourage colonial settlement.

PMID- 23559043
TI  - Saccharopolyspora dendranthemae sp. nov. a halotolerant endophytic actinomycete
      isolated from a coastal salt marsh plant in Jiangsu, China.
AB  - A halotolerant actinomycete strain, designated strain KLBMP 1305(T), was isolated
      from a salt marsh plant Dendranthema indicum (Linn.) Des Moul collected from the
      coastal region of Nantong, Jiangsu Province, in east China and was studied in
      detail for its taxonomic position. Phylogenetic analysis based on the 16S rRNA
      gene sequence revealed that strain KLBMP 1305(T) is a member of the genus
      Saccharopolyspora. The 16S rRNA gene sequence similarity indicated that strain
      KLBMP 1305(T) was most closely related to 'Saccharopolyspora pathumthaniensis'
      S582(T) (99.31 %), 'Saccharopolyspora endophytica' YIM 61095(T) (99.17 %) and
      Saccharopolyspora tripterygii YIM 65359(T) (99.15 %); similarity to other type
      strains of the genus Saccharopolyspora was <97.2 %. The organism had chemical and
      morphological features consistent with its classification in the genus
      Saccharopolyspora such as meso-diaminopimelic acid as the diagnostic diamino acid
      in the cell wall peptidoglycan and arabinose and galactose as the diagnostic
      sugars. The predominant menaquinone was MK-9(H4). The polar lipids detected were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylcholine, an unknown glycolipid and an unknown lipid. The major fatty
      acids were iso-C16:0, iso-C15:0, anteiso-C15:0, anteiso-C17:0 and sum in feature
      8 (18:1omega7c/18:1omega6c). The G+C content of the genomic DNA of the type
      strain was 68.7 mol%. DNA-DNA relatedness data, together with phenotypic
      differences, clearly distinguished the isolate from its closest relatives. On the
      basis of these phenotypic and genotypic data, the isolate represents a novel
      species, for which the name Saccharopolyspora dendranthemae sp. nov. is proposed.
      The type strain is KLBMP 1305(T) (=KCTC 19889(T) = NBRC 108675(T)).

PMID- 23559046
TI  - [A trajectory of British health professionals, 1815-1858].
AB  - The article recounts the process of regulating the health professions in England
      from 1815 to 1858. Impelled by the period's epidemics, this was also the time of
      the sanitary reform, in which health professionals devoted themselves to aiding
      the ill. Since the technical attributions of each type of professional were not
      clearly defined, this field of un-regulated practices became divided into two
      areas: the provision of medical advice and the manipulation of formulas. Three
      important measures changed the field of medical and pharmacological practices:
      the Apothecaries Act (1815), the Pharmacy Act (1852), and the Medical Act (1858).
      These laws were a mixed reflection of the interests of the State, medical
      professionals, and British society.

PMID- 23559047
TI  - [Historical aspects of the institutionalization of adolescent healthcare in the
      state of Sao Paulo, 1970-1990].
AB  - The article explores historical aspects of integral healthcare for adolescents in
      the state of Sao Paulo, particularly in regard to the implementation of
      pioneering services and programs. Against the backdrop of Brazil's social and
      political context during this period, it contextualizes the challenges, clashes,
      and difficulties that arose within the institutions involved in developing this
      field, from the perspectives of clinical medicine and of collective health.
      Grounded on documental material, the study re-examines the construction of groups
      of expertise and of the field of adolescent health care as part of the
      dialectical interplay between the construction of a new area of medical practice
      based on clinical work and a field of knowledge and practices in collective
      health based on integral health care of an interdisciplinary, inter-sectoral
      nature.

PMID- 23559048
TI  - A Brazilian in the Reich of Wilhelm II: Henrique da Rocha Lima, Brazil-Germany
      relations and the Instituto Oswaldo Cruz, 1901-1909.
AB  - This article follows the career of the Brazilian physician Henrique da Rocha
      Lima, one of the first to join the group of young researchers working at the
      Instituto Soroterapico de Manguinhos (Instituto Oswaldo Cruz). It describes his
      first voyage to Germany where he specialized in microbiology and pathological
      anatomy, training that shaped his subsequent professional identity. The tensions
      and dilemmas experienced by Rocha Lima provide an insight into what it meant to
      dedicate oneself to a scientific career in Brazil at the start of the twentieth
      century. They also reveal the importance of the relations with the German
      speaking world for the experimental medicine that became established under the
      leadership of Oswaldo Cruz.

PMID- 23559049
TI  - Unhealthiness, disease, and immigration: german views of Brazil.
AB  - In the period stretching from the birth of the German Empire through the rise of
      Nazism and the Third Reich, the article explores the themes of unhealthiness,
      acclimatization, and disease in Brazil as found in the writings of German
      speaking travelers who were involved with the immigration question. On the one
      hand, Brazil was considered quite suitable as an immigration destination,
      especially in comparison to Africa and the United States; on the other,
      immigrants might be scared off by its climate and by the menace of diseases like
      yellow fever, malaria, tuberculosis, and worms, along with insect plagues and
      venomous animals. The question here is how authors with different profiles -
      'colonial politicians,' immigrants, men of letters who were forced to emigrate,
      and scientists - approached these 'threats,' considering that their readers would
      be (potential) immigrants.

PMID- 23559050
TI  - [The policy of disseminating Germanism through the Bayer periodicals Revista
      Terapeutica and O Farmaceutico Brasileiro].
AB  - The article analyzes two periodicals published by the chemical and pharmaceutical
      company Bayer - as they played into scientific relations between Brazil and
      Germany. At the close of World War I, a number of countries, including Brazil,
      broke off political, economic, and scientific relations with Germany. Germany's
      medical and scientific community moved to implement a policy of disseminating
      Germanism through science and medicine, aimed above all at Latin America.
      Germany's chemical and pharmaceutical industry was impacted by this policy, as it
      both supported and was a beneficiary of the endeavor to disseminate German
      science and to promote international scientific exchange, which opened new
      markets. In Brazil, these efforts were backed by physician Renato Kehl.

PMID- 23559051
TI  - The Revista Medica project: medical journals as instruments of German foreign
      cultural policy towards Latin America, 1920-1938.
AB  - After the First World War, foreign cultural policy became one of the few fields
      in which Germany could act with relative freedom from the restrictions imposed by
      the Treaty of Versailles. In this context the Hamburg doctors Ludolph Brauer,
      Bernhard Nocht and Peter Muhlens created the Revista Medica de Hamburgo (as of
      1928 Revista Medica Germano-Ibero-Americana), a monthly medical journal in
      Spanish (and occasionally in Portuguese), to increase German influence especially
      in Latin American countries. The focus of this article is on the protagonists of
      this project, the Hamburg doctors, the Foreign Office in Berlin, the German
      pharmaceutical industry, and the publishing houses involved.

PMID- 23559052
TI  - [The emergence of traditional indigenous medicine in the public policy field].
AB  - The article explores the emergence of traditional indigenous medicine as an
      object of discourse within the field of public policy and indigenous health.
      There are a gamut of meanings that inform the notion of traditional indigenous
      medicine in this field and they are steadily being revised and/or created in
      concrete dialogical situations, which endows them with an emergent nature. If
      official discourses use the power of naming to conceptualize traditional
      medicine, indigenous discourse designates knowledge and practices of self
      attention rooted in specific local contexts. Public policy is appropriated and
      indigenized by indigenous peoples, gaining new meanings and influencing the
      sociocultural re-organization of health care.

PMID- 23559053
TI  - [Rudolf Kraus in search of the "gold of science": tropical diversity and the
      development of new treatments, 1913-1923].
AB  - Based on the career of Rudolf Kraus, the article analyzes the search for cures to
      infectious diseases in tropical regions in the early twentieth century, focusing
      especially on Kraus' development of new biological treatments like sera,
      vaccines, and protein solutions. At that time, the world's tropical regions were
      often portrayed as more propitious for research, given the larger number of
      organisms that could be identified in these realms and an allegedly lower level
      of peer competition as well. The tropics were thus seen as an oasis for
      microbiological research. Kraus dedicated himself to the production of various
      products of biological origin, but he failed to achieve his hoped-for success
      with many of them.

PMID- 23559054
TI  - [Emil Kraepelin and psychiatric science in Rio de Janeiro, 1903-1933].
AB  - The article addresses the penetration of German psychiatric science in early
      twentieth-century Brazil. More specifically, it explores how the theory and
      practices of Emil Kraepelin were absorbed by both Juliano Moreira, director of
      the National Hospital for the Insane (Hospicio Nacional de Alienados) and of the
      agency for Assistance to the Insane (Assistencia a Alienados) in the Federal
      District (Rio de Janeiro), and also by the circle of physicians with close ties
      to Moreira from 1903 to 1933. It discusses the ways in which Kraepelin's work was
      adopted, taking into account the day's medical-mental repertoire, the political
      and scientific context, and the controversies within the Brazilian psychiatric
      field. Lastly, the study analyzes these choices based on the prevailing relations
      between Brazilian and German psychiatry back then.

PMID- 23559055
TI  - [The photographic archive of the Instituto Brasileiro de Geografia e Estatistica
      and Tibor Jablonszky's view of female labor].
AB  - Shining a light on the photographic archive of geographic missions assigned to do
      reconnaissance of the country's territory, sponsored by the Brazilian Institute
      of Geography and Statistics, the article describes the conditions under which
      this archive was compiled and how it can serve as a historical source. It
      addresses the presentation of images and the range of topics and places found in
      Tibor Jablonszky's work as far as the representations that this photographer
      constructed of female labor in Brazil during the 1950s and 1960s, from the
      viewpoint of a photographer working for a government agency.

PMID- 23559056
TI  - [Science, telegraphs, and geography: military engineers in the Rondon Commission,
      1907-1915].
AB  - The article focuses on the work to demarcate borders and chart the Brazilian
      northwest from 1907 to 1915, a project aimed at national integration and
      undertaken by the Rondon Commission for the Construction of Telegraph Lines from
      Mato Grosso to Amazonas, which was organized by the Brazilian ministries of War,
      Transportation and Public Works, and Agriculture. The study explores the ways in
      which topographic surveys were conducted by the military engineers sent by the
      Ministry of War and also endeavors to understand their activities in the field.
      Of further interest are the demands made by the War Ministry and how they were
      responded to within the commission.

PMID- 23559057
TI  - [Doctor's recommendations concerning the education of the problem child: a study
      of mental hygiene handbooks, 1939-1947].
AB  - The article presents the initial findings of a study on guidelines for the
      education of the problem child, as found in handbooks on children's hygiene
      written by Brazilian physicians. These books, whose target audience comprised the
      mothers and teachers who were in charge of educating these children, sought to
      explain the origin of the most common behavioral problems and offered
      instructions on how to overcome these difficulties, which jeopardized the child's
      development and also its adjustment to family and school. A preliminary analysis
      of two manuals approached from the perspective of the theoretical framework of
      Foucault and other authors on governmentality suggests that the books in question
      endeavored first and foremost to orient adults to make good use of power in their
      relations with children.

PMID- 23559058
TI  - [The American Sociological Association's Medical Sociology Section turns fifty
      and the Journal of Health and Social Behavior celebrates].

PMID- 23559059
TI  - [The first Brazilian scientific voyage: the imperial scientific commission].

PMID- 23559060
TI  - [Disease of Chagas, disease of Brazil].

PMID- 23559061
TI  - [David Bloor's letter of intentions].

PMID- 23559062
TI  - [Bacteria or parasite?bacteria is also a parasite].

PMID- 23559063
TI  - Design and development of a sensorized wireless toy for measuring infants' manual
      actions.
AB  - The development of grasping is an important milestone that infants encounter
      during the first months of life. Novel approaches for measuring infants' manual
      actions are based on sensorized platform usable in natural settings, such as
      instrumented wireless toys that could be exploited for diagnosis and
      rehabilitation purposes. A new sensorized wireless toy has been designed and
      developed with embedded pressure sensors and audio-visual feedback. The
      fulfillment of clinical specifications has been proved through mechanical and
      electrical characterization. Infants showed a good grade of acceptance to such
      kind of tools, as confirmed by the results of preliminary tests that involved
      nine healthy infants: the dimensions fulfill infants' anthropometrics, the device
      is robust and safe, the acquired signals are in the expected range and the
      wireless communication is stable. Although achieved only through preliminary
      tests, such results confirm the hypothesis that this typology of instrumented
      toys could be useful for quantitative monitoring and measuring infants' motor
      development and ready to be evaluated for assessing motor skills through
      appropriate clinical trials.

PMID- 23559064
TI  - Transcranial magnetic stimulation in the assessment of motor cortex excitability
      and treatment of drug-resistant major depression.
AB  - Major depression is one of the leading causes of disabling condition worldwide
      and its treatment is often challenging and unsatisfactory, since many patients
      become refractory to pharmacological therapies. Transcranial magnetic stimulation
      (TMS) is a noninvasive neurophysiological investigation mainly used to study the
      integrity of the primary motor cortex excitability and of the cortico-spinal
      tract. The development of paired-pulse and repetitive TMS (rTMS) paradigms has
      allowed investigators to explore the pathophysiology of depressive disorders and
      other neuropsychiatric diseases linked to brain excitability dysfunctions.
      Repetitive transcranial magnetic stimulation has also therapeutic and
      rehabilitative capabilities since it is able to induce changes in the
      excitability of inhibitory and excitatory neuronal networks that may persist in
      time. However, the therapeutic effects of rTMS on major depression have been
      demonstrated by analyzing only the improvement of neuropsychological performance.
      The aim of this study was to investigate cortical excitability changes on 12
      chronically-medicated depressed patients (test group) after rTMS treatment and to
      correlate neurophysiological findings to neuropsychological outcomes. In detail,
      we assessed different parameters of cortical excitability before and after active
      rTMS in the test group, then compared to those of 10 age-matched depressed
      patients (control group) who underwent sham rTMS. In line with previous studies,
      at baseline both groups exhibited a significant interhemispheric difference of
      motor cortex excitability. This neurophysiological imbalance was then reduced in
      the patients treated with active rTMS, resulting also in a clinical benefit as
      demonstrated by the improvement in neuropsychological test scores. On the
      contrary, after sham rTMS, the interhemispheric difference was still evident in
      the control group. The reported clinical benefits in the test group might be
      related to the plastic remodeling of synaptic connection induced by rTMS
      treatment.

PMID- 23559065
TI  - Maternally deposited germline piRNAs silence the tirant retrotransposon in
      somatic cells.
AB  - Transposable elements (TEs), whose propagation can result in severe damage to the
      host genome, are silenced in the animal gonad by Piwi-interacting RNAs (piRNAs).
      piRNAs produced in the ovaries are deposited in the embryonic germline and
      initiate TE repression in the germline progeny. Whether the maternally
      transmitted piRNAs play a role in the silencing of somatic TEs is however
      unknown. Here we show that maternally transmitted piRNAs from the tirant
      retrotransposon in Drosophila are required for the somatic silencing of the TE
      and correlate with an increase in histone H3K9 trimethylation an active tirant
      copy.

PMID- 23559066
TI  - Phosphorylation of mitophagy and pexophagy receptors coordinates their
      interaction with Atg8 and Atg11.
AB  - The selective autophagy receptors Atg19 and Atg32 interact with two proteins of
      the core autophagic machinery: the scaffold protein Atg11 and the ubiquitin-like
      protein Atg8. We found that the Pichia pastoris pexophagy receptor, Atg30, also
      interacts with Atg8. Both Atg30 and Atg32 interactions are regulated by
      phosphorylation close to Atg8-interaction motifs. Extending this finding to
      Saccharomyces cerevisiae, we confirmed phosphoregulation for the mitophagy and
      pexophagy receptors, Atg32 and Atg36. Each Atg30 molecule must interact with both
      Atg8 and Atg11 for full functionality, and these interactions occur independently
      and not simultaneously, but rather in random order. We present a common model for
      the phosphoregulation of selective autophagy receptors.

PMID- 23559067
TI  - The interplay between RPGR, PDEdelta and Arl2/3 regulate the ciliary targeting of
      farnesylated cargo.
AB  - Defects in primary cilia result in human diseases known as ciliopathies. The
      retinitis pigmentosa GTPase regulator (RPGR), mutated in the most severe form of
      the eye disease, is located at the transition zone of the ciliary organelle. The
      RPGR-interacting partner PDEdelta is involved in trafficking of farnesylated
      ciliary cargo, but the significance of this interaction is unknown. The crystal
      structure of the propeller domain of RPGR shows the location of patient mutations
      and how they perturb the structure. The RPGR.PDEdelta complex structure shows
      PDEdelta on a highly conserved surface patch of RPGR. Biochemical experiments and
      structural considerations show that RPGR can bind with high affinity to cargo
      loaded PDEdelta and exposes the Arl2/Arl3-binding site on PDEdelta. On the basis
      of these results, we propose a model where RPGR is acting as a scaffold protein
      recruiting cargo-loaded PDEdelta and Arl3 to release lipidated cargo into cilia.

PMID- 23559068
TI  - Membrane contact sites--an interesting species, an interesting mix.

PMID- 23559069
TI  - SpoIIIE mechanism of directional translocation involves target search coupled to
      sequence-dependent motor stimulation.
AB  - SpoIIIE/FtsK are membrane-anchored, ATP-fuelled, directional motors responsible
      for chromosomal segregation in bacteria. Directionality in these motors is
      governed by interactions between specialized sequence-recognition modules
      (SpoIIIE-gamma/FtsK-gamma) and highly skewed chromosomal sequences (SRS/KOPS).
      Using a new combination of ensemble and single-molecule methods, we dissect the
      series of steps required for SRS localization and motor activation. First, we
      demonstrate that SpoIIIE/DNA association kinetics are sequence independent, with
      binding specificity being uniquely determined by dissociation. Next, we show by
      single-molecule and modelling methods that hexameric SpoIIIE binds DNA non
      specifically and finds SRS by an ATP-independent target search mechanism, with
      ensuing oligomerization and binding of SpoIIIE-gamma to SRS triggering motor
      stimulation. Finally, we propose a new model that provides an entirely new
      interpretation of previous observations for the origin of SRS/KOPS-directed
      translocation by SpoIIIE/FtsK.

PMID- 23559070
TI  - Changes of podocyte p130Cas in diabetic conditions.
AB  - BACKGROUND: Proteinuria results from increased glomerular permeability and is
      associated with retraction and effacement of the highly specialized
      interdigitating podocyte foot processes. In podocytes (glomerular epithelial
      cells [GECs]), p130Cas localizes diffusely to the cytoplasm and connects focal
      adhesion proteins and kinases to the glomerular basement membrane and adapter
      proteins of slit diaphragm insertion sites. METHODS: To investigate whether high
      glucose (HG) and advanced glycosylation end products (AGEs) induce quantitative
      and distributional changes of podocyte p130Cas protein, a docking protein
      connecting F-actin fibers to the glomerular basement membrane and adapter
      proteins, we cultured rat GECs (r-GECs) and mouse GECs (m-GECs) under (i) normal
      glucose (5 mM = control), (ii) HG (30 mM), (iii) AGE-added or (iv) HG plus AGE
      added conditions. We also prepared streptozotocin-induced diabetic renal tissues.
      RESULTS: We found that p130Cas stainings were located in peripheral cytoplasm of
      r-GECs and m-GECs as dots in linear alignment, partially colocalized with actin
      binding proteins such as synaptopodin and alpha-actinin, and locally connected to
      the ends of actin filaments. In diabetic conditions, the intensities of p130Cas
      stainings were diminished in more pathological HG plus AGE-added condition of r
      GECs and m-GECs and in chronic diabetic renal tissues. p130Cas protein was
      decreased significantly by HG, AGE and HG plus AGE in both cells compared with
      normal glucose or osmotic control conditions. p130Cas mRNA expression levels were
      also suppressed similarly in diabetic conditions. CONCLUSION: We suggest that
      diabetic conditions modulate the quantitative and distributional changes of
      podocyte p130Cas and therefore affect the filtration function of podocytes.

PMID- 23559071
TI  - TLR4 signaling induces retinoic acid-inducible gene-I and melanoma
      differentiation-associated gene 5 in mesangial cells.
AB  - BACKGROUND: It is known that recognition of bacterial lipopolysaccharide (LPS)
      and various endogenous ligands by Toll-like receptor 4 (TLR4) induces
      inflammatory reactions. However, the role of TLR4 activation in mesangial
      inflammation remains to be elucidated. Retinoic acid-inducible gene-I (RIG-I) and
      melanoma differentiation-associated gene 5 (MDA5) are putative RNA helicases and
      are involved in immune and inflammatory reactions. The purpose of the present
      study was to investigate the implication of RIG-I and MDA5 in TLR4 signaling in
      mesangial cells. METHODS: Normal human mesangial cells in culture were treated
      with LPS. Expression of RIG-I, MDA5, interferon-beta (IFN-beta), CXCL10 and CXCL8
      was examined using real-time RT-PCR, Western blotting and ELISA. The cells were
      also subjected to RNA interference against TLR4, IFN-beta, RIG-I or MDA5.
      RESULTS: LPS induced the expression of IFN-beta, RIG-I, MDA5, CXCL8 and CXCL10 in
      human mesangial cells. RNA interference against either TLR4 or IFN-beta inhibited
      LPS-induced RIG-I and MDA5 expression. Knockdown of TLR4, IFN-beta, RIG-I or MDA5
      resulted in decreased induction of CXCL10, while only TLR4 knockdown inhibited
      CXCL8 induction. CONCLUSIONS: TLR4 signaling induces the expression of RIG-I and
      MDA5 in mesangial cells. RIG-I and MDA5 may be involved in inflammatory reactions
      by regulating CXCL10 expression in the downstream of TLR4 signaling in human
      mesangial cells.

PMID- 23559073
TI  - The zebrafish as a model for nociception studies.
AB  - Nociception is the sensory mechanism used to detect cues that can harm an
      organism. The understanding of the neural networks and molecular controls of the
      reception of pain remains an ongoing challenge for biologists. While we have made
      significant progress in identifying a number of molecules and pathways that are
      involved in transduction of noxious stimuli, from the skin through the sensory
      receptor cell and from this to the spinal cord on into the central nervous
      system, we still lack a clear understanding of the perceptual processes, the
      responses to pain and the regulation of pain perception. Mice and rat animal
      models have been extensively used for nociception studies. However, the study of
      pain and noiception in these organisms can be rather laborious, costly and time
      consuming. Conversely, the use of Drosophila and Caenorhabditis elegans may be
      affected by the large evolutionary distance between these animals and humans. We
      outline here the reasons why zebrafish presents a new and attractive model for
      studying pain reception and responses and the most interesting findings in the
      study of nociception that have been obtained using the zebrafish model.

PMID- 23559074
TI  - Melting of metallic electrodes and their flowing through a carbon nanotube
      channel within a device.
AB  - Evidence is presented of a new cause of Joule heating within a simple electronic
      device involving a multiwalled carbon nanotube (CNT) mounted on two metal
      electrodes forming an electrical circuit. This time-resolved, high-resolution in
      situ observation of metal electrode material melting and its flow driven by the
      thermomigration and electromigration forces through the CNT channel sheds an
      additional light on the effects affecting the real electrical performance of the
      CNT-based devices.

PMID- 23559075
TI  - Characterization of rhodamine self-assembled films using desorption electrospray
      ionization mass spectrometry.
AB  - Growth process information and molecular structure identification are very
      important for characterization of self-assembled films. Here, we explore the
      possible application of desorption electrospray ionization mass spectrometry
      (DESI-MS) that provides the assembled information of rhodamine B (Rh B) and
      rhodamine 123 (Rh 123) films. With the help of lab-made DESI source, two
      characteristic ions [Rh B](+) and [Rh 123](+) are observed directly in the open
      environment. To evaluate the reliability of this technique, a comparative study
      of ultraviolet-visible (UV-vis) spectroscopy and our method is carried out, and
      the result shows good correlation. According to the signal intensity of
      characteristic ions, the layer-by-layer adsorption process of dyes can be
      monitored, and the thicknesses of multilayer films can also be comparatively
      determined. Combining the high sensitivity, selectivity, and speed of mass
      spectrometry, the selective adsorption of similar structure molecules under
      different pH is recognized easily from extracted ion chronograms. The variation
      trend of dyes signalling intensity with concentration of polyelectrolyte is
      studied as well, which reflects the effect of surface charge on dyes deposition.
      Additionally, the desorption area, surface morphology, and thicknesses of
      multilayer films are investigated using fluorescence microscope, scanning
      electron microscope (SEM), and atomic force microscopy (AFM), respectively.
      Because the desorption area was approximately as small as 2 mm(2), the
      distribution situation of organic dyes in an arbitrary position could be gained
      rapidly, which means DESI-MS has advantages on in situ analysis.

PMID- 23559076
TI  - Management of castrate resistant prostate cancer-recent advances and optimal
      sequence of treatments.
AB  - Until 2010, chemotherapy with docetaxel was the only approved agent for treatment
      of metastatic castrate resistant prostate cancer (mCRPC). Since then, the
      therapeutic landscape of mCRPC has changed rapidly. Multiple novel agents have
      received regulatory approval after demonstrating improved overall survival in
      separate randomized Phase 3 studies. These include immunotherapeutic agent
      sipuleucel-T, androgen axis inhibitors abiraterone and enzalutamide, and a novel
      microtubule inhibitor cabazitaxel. More recently, radium-223, a bone-targeting
      alpha emitting radiopharmaceutical, was reported to improve skeletal related
      events, as well as overall survival in a Phase 3 randomized study. Additionally,
      there are several promising agents in the advanced stages of clinical
      development. Here, we describe the agents recently shown to improve overall
      survival, and those that have reached the advanced stages of development in Phase
      3 clinical trials. We will also propose a strategy for optimal sequencing of
      these agents in the treatment of mCRPC.

PMID- 23559077
TI  - Central venous-arterial pCO2 difference as a tool in resuscitation of septic
      patients.
AB  - PURPOSE: To investigate the interchangeability of mixed and central venous
      arterial carbon dioxide differences and the relation between the central
      difference (pCO2 gap) and cardiac index (CI). We also investigated the value of
      the pCO2 gap in outcome prediction. METHODS: We performed a post hoc analysis of
      a well-defined population of 53 patients with severe sepsis or septic shock.
      Mixed and central venous pCO2 were determined earlier at a 6 h interval (T = 0 to
      T = 4) during the first 24 h after intensive care unit (ICU) admittance. The
      population was divided into two groups based on pCO2 gap (cut off value 0.8 kPa).
      RESULTS: The mixed pCO2 difference underestimated the central pCO2 difference by
      a mean bias of 0.03 +/- 0.32 kPa (95 % limits of agreement: -0.62-0.58 kPa). We
      observed a weak relation between pCO2 gap and CI. The in hospital mortality rate
      was 21 % (6/29) for the low gap group and 29 % (7/24) for the high gap group; the
      odds ratio was 1.6 (95 % CI 0.5-5.5), p = 0.53. At T = 4 the odds ratio was 5.3
      (95 % CI 0.9-30.7); p = 0.08. CONCLUSIONS: From a practical perspective, the
      clinical utility of central venous pCO2 values is of potential interest in
      determining the venous-arterial pCO2 difference. The likelihood of a bad outcome
      seems to be enhanced when a high pCO2 gap persists after 24 h of therapy.

PMID- 23559079
TI  - Factors that contribute to physician variability in decisions to limit life
      support in the ICU: a qualitative study.
AB  - PURPOSE: Our aim was to explore reasons for physician variability in decisions to
      limit life support in the intensive care unit (ICU) utilizing qualitative
      methodology. METHODS: Single center study consisting of semi-structured
      interviews with experienced physicians and nurses. Seventeen intensivists from
      medical (n = 7), surgical (n = 5), and anesthesia (n = 5) critical care
      backgrounds, and ten nurses from medical (n = 5) and surgical (n = 5) ICU
      backgrounds were interviewed. Principles of grounded theory were used to analyze
      the interview transcripts. RESULTS: Eleven factors within four categories were
      identified that influenced physician variability in decisions to limit life
      support: (1) physician work environment-workload and competing priorities, shift
      changes and handoffs, and incorporation of nursing input; (2) physician
      experiences-of unexpected patient survival, and of limiting life support in
      physician's family; (3) physician attitudes-investment in a good surgical
      outcome, specialty perspective, values and beliefs; and (4) physician
      relationship with patient and family-hearing the patient's wishes firsthand,
      engagement in family communication, and family negotiation. CONCLUSIONS: We
      identified several factors which physicians and nurses perceived were important
      sources of physician variability in decisions to limit life support. Ways to
      raise awareness and ameliorate the potentially adverse effects of factors such as
      workload, competing priorities, shift changes, and handoffs should be explored.
      Exposing intensivists to long term patient outcomes, formalizing nursing input,
      providing additional training, and emphasizing firsthand knowledge of patient
      wishes may improve decision making.

PMID- 23559078
TI  - New insights into fluid resuscitation.
AB  - Recent high-quality randomised-controlled trials comparing the effects of
      hydroxyethyl starch (HES) preparations and crystalloids for fluid resuscitation
      in critically ill patients have demonstrated an increased risk of death and use
      of renal replacement therapy (RRT). Consequently, a number of systematic reviews
      incorporating these new results have been published that have consistently
      demonstrated an increased risk of death and use of RRT associated with HES
      solutions, regardless of type of HES and dose administered, both in general
      intensive care patients and in those with severe sepsis. These effects become
      apparent in the post-resuscitation period and may relate to increased tissue
      accumulation associated with HES. These results question the clinical role of
      semi-synthetic colloids for fluid resuscitation and mandate a reappraisal about
      how these fluids are administered to critically ill patients, specifically
      considering the potential for toxicity.

PMID- 23559080
TI  - Changes in serum adhesion molecules, chemokines, cytokines, and tissue remodeling
      factors in euthyroid women without thyroid antibodies who are at risk for
      autoimmune thyroid disease: a hypothesis on the early phases of the endocrine
      autoimmune reaction.
AB  - BACKGROUND: The target glands in spontaneous animal models of endocrine
      autoimmune disease show, prior to the autoimmune reaction, growth and connective
      tissue abnormalities, whereas the autoimmune reaction is initiated by an early
      accumulation of macrophages and dendritic cells in the target glands. AIM: The
      aim of the study was to test the hypothesis that serum factors related to these
      growth and connective tissue abnormalities and the early accumulation of immune
      cells, ie, tissue growth/remodeling factors, adhesion molecules, chemokines, and
      pro- and anti-inflammatory cytokines, are related to thyroid peroxidase
      autoantibodies (TPO-Abs) seroconversion in subjects at risk to develop autoimmune
      thyroid disease (AITD). DESIGN: A controlled study on 64 TPO-Ab-negative
      euthyroid female relatives with at least 1 first- or second-degree relative with
      documented autoimmune hyper- or hypothyroidism, 32 of whom did and 32 who did not
      seroconvert to TPO-Ab positivity in 5-year follow-up. The relatives were compared
      with 32 healthy controls. In all subjects we measured serum levels of chemokine
      (C-C motif) ligand (CCL)-2, CCL3, CCL4, soluble vascular cell adhesion molecule,
      soluble intercellular adhesion molecule-1, thrombospondin-1, vascular endothelial
      growth factor-A, angiopoietin 1 receptor-2, metalloproteinase-13, platelet
      derived growth factor-BB, fibronectin, IL-1beta, IL-6, TNF-alpha, IL-10, and
      growth differentiation factor-15 by multiplex (cytometric bead array) or a single
      commercial ELISA. RESULTS: Both seroconverting and nonseroconverting family
      members showed an up-regulation of fibronectin and a down-regulation of platelet
      derived growth factor-BB and the adhesion and migration factors CCL2, CCL4,
      soluble vascular cell adhesion molecule-1, angiopoietin 1 receptor-2, and
      metalloproteinase-13. The seroconverters differed from the nonseroconverters by
      an up-regulation of the proinflammatory compounds Il-1beta, IL-6, and CCL3.
      CONCLUSION: This study shows that euthyroid females within AITD families show a
      characteristic pattern of abnormalities in serum levels of tissue remodeling
      factors, growth factors, chemokines, (vascular) adhesion molecules, and cytokines
      prior to the occurrence of TPO-Abs in serum. The results provide proof of
      principle that preseroconversion stages and seroconversion to AITD might be
      predicted using serum analytes related to growth/connective tissue abnormalities
      and migration/accumulation abnormalities of macrophages and dendritic cells.

PMID- 23559081
TI  - Association between abdominal obesity and fracture risk: a prospective study.
AB  - CONTEXT: Higher body weight is associated with greater bone mineral density (BMD)
      and lower fracture risk. However, the relationship between abdominal fat mass
      (aFM) and fracture risk is unclear because of limited prospective data. The
      present study sought to examine the association between aFM, BMD, and fracture
      risk. METHODS: The study was designed as a prospective investigation, in which a
      sample of 1126 participants (360 men and 766 women) aged 50 years or older had
      been continuously followed up for an average of 5 years. The mean age of
      participants was 71 years (range, 57-94 years). At baseline, BMD at the femoral
      neck and lumbar spine and aFM were measured by dual-energy X-ray absorptiometry.
      The incidence of low-trauma and nonpathological fractures was ascertained
      prospectively from X-ray reports. RESULTS: During the follow-up period, 19 men
      and 107 women had sustained a fracture. In women, each 1-kg lower aFM was
      associated with a 50% higher risk of fracture (hazard ratio [HR], 1.50; 95%
      confidence interval [CI], 1.10-2.05) after adjustment for age, femoral neck BMD,
      falls, stature, physical activity, and prior fracture. Subgroup analysis by
      fracture type found that the association was mainly observed in clinical
      vertebral fracture (HR, 1.96; 95% CI, 1.22-3.13). In men, although there was no
      statistically significant association between aFM and fracture risk (HR, 1.15;
      95% CI, 0.58-2.25), the strength of this finding is affected negatively by the
      low number of fractures. CONCLUSIONS: Lower abdominal fat was significantly
      associated with an higher fracture risk in women.

PMID- 23559082
TI  - Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a
      population with endemic vitamin D deficiency.
AB  - BACKGROUND: Vitamin D (vD) deficiency in pregnancy is a global health problem and
      the amount of vD supplementation to prevent vD deficiency is controversial.
      OBJECTIVE: The objective of the study was to determine effectiveness and safety
      of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a
      randomized controlled trial in population in which vD deficiency is endemic.
      DESIGN/METHODS: Arab women were randomized at 12-16 weeks of gestation to 400,
      2000, and 4000 IU/d vD3, which were continued to delivery. Serum 25
      hydroxyvitamin D [25(OH)D] concentrations were measured during pregnancy and at
      delivery. The primary outcome was the maternal and cord blood 25(OH)D, and the
      secondary outcomes were the achievement of sufficient serum 25(OH)D of 32 ng/mL
      or greater (>=80 nmol/L) at delivery. SETTING: The locations were primary care
      and tertiary perinatal care centers. RESULTS: Of 192 enrolled, 162 (84%)
      continued to delivery. Mean serum 25(OH)D of 8.2 ng/mL (20.5 nmol/L) at
      enrollment was low. Mean serum 25(OH)D concentrations at delivery and in cord
      blood were significantly higher in the 2000 and 4000 IU than the 400 IU/d group
      (P < .001) and was highest in the 4000 IU/d group. The percent who achieved
      25(OH)D greater than 32 ng/mL and greater than 20 ng/mL concentrations in mothers
      and infants was highest in 4000 IU/d group. Safety measurements were similar by
      group and no adverse event related to vD supplementation. CONCLUSIONS: Vitamin D
      supplementation of 2000 and 4000 IU/d appeared safe in pregnancy, and 4000 IU/d
      was most effective in optimizing serum 25(OH)D concentrations in mothers and
      their infants. These findings could apply to other populations in which vD
      deficiency is endemic.

PMID- 23559083
TI  - Thyroid cancer cell resistance to gefitinib depends on the constitutive oncogenic
      activation of the ERK pathway.
AB  - CONTEXT: Poorly differentiated thyroid carcinomas are refractory to common
      anticancer therapies, and novel inhibitors are being tested in these deadly
      malignancies. The epidermal growth factor receptor (EGFR) tyrosine kinase
      represents an attractive target for treatment because it is up-regulated in
      thyroid cancer and plays a role in cancer progression. However, EGFR inhibitors
      have provided poor results in thyroid carcinomas. OBJECTIVE: We evaluated the
      possible mechanism underlying the resistance of thyroid cancer cells to EGFR
      inhibitors. DESIGN: We tested the effect of the EGFR tyrosine kinase inhibitor
      gefitinib in a panel of thyroid cancer cell lines. RESULTS: We found that in most
      of the cell lines, although gefitinib inhibited EGFR phosphorylation, it was
      poorly effective in reducing cell viability. gefitinib, however, was able to
      inhibit epidermal growth factor-induced cell migration and matrix invasion. In
      most thyroid cancer cell lines, gefitinib significantly inhibited Akt
      phosphorylation by inhibiting EGFR activation, but it had limited or no effect on
      ERK phosphorylation. The poor cell response to gefitinib was associated with
      genetic alterations, leading to constitutive activation of the ERK pathway,
      including BRAF(V600E) and HRAS(G12A/Q61R) mutations and RET/PTC1 rearrangement.
      When BRAF(V600E)-positive thyroid cancer cells were incubated with the specific
      BRAF inhibitor PLX4032, sensitivity to gefitinib was restored. Similar results
      were obtained with rat sarcoma and RET/papillary thyroid cancer inhibitors.
      CONCLUSIONS: These results indicate that thyroid cancer resistance to gefitinib
      is due to the constitutive activation of the mitogenic pathway by either signals
      downstream of EGFR or other tyrosine kinase receptors. This resistance can be
      overcome by the combined use of selective inhibitors.

PMID- 23559085
TI  - Is subclinical hypothyroidism a cardiovascular risk factor in the elderly?
AB  - CONTEXT: The negative impact of subclinical hypothyroidism (sHT) on
      cardiovascular risk, widely recognized in young adults (aged <55-60 y), is still
      debated in the elderly (>65 y), especially in the oldest olds (>80 y). EVIDENCE
      ACQUISITION: We searched Medline for reports published with the following search
      terms: "hypothyroidism," "subclinical hypothyroidism," "ageing," "elderly," "L
      thyroxin," "thyroid," "guidelines," "treatment," "quality of life,"
      "cardiovascular risk," "heart failure," "coronary heart disease" (CHD),
      "atherosclerosis," and "endothelial dysfunction." We limited our search to
      reports in English published after 1980, although we incorporated some reports
      published before 1980. We supplemented the search with records from personal
      files, textbooks, and relevant articles. Analyzed parameters included the
      epidemiology of thyroid failure, the effect of thyroid hormone on the aging
      process, cardiovascular function, and CHD risk factors. We also included the
      potential benefits of L-T4 therapy on the quality of life, cardiovascular events,
      and survival. EVIDENCE SYNTHESIS: TSH levels increase with age, even in older
      people without thyroid disease. Most longitudinal studies show an increased risk
      for CHD events and mortality in sHT participants. This increase is less evident
      in the elderly, mainly in cases of serum TSH values above 10 mIU/L. Lower
      mortality rate in a cohort of the oldest olds (>85 y) has been reported.
      CONCLUSIONS: sHT in older people should be not regarded as a unique condition,
      and moderately old patients (aged <70-75 y) could be considered clinically
      similar to the adult population, albeit with a higher optimal TSH target value.
      Conversely, the oldest old subjects should be carefully followed with a wait-and
      see strategy, generally avoiding hormonal treatment. The decision to treat
      elderly people is still an unresolved clinical challenge--first, due to a lack of
      appropriately powered randomized controlled trials of L-T4 in sHT patients,
      examining cardiovascular hard endpoints in various classes of age; and second,
      because of the negative effects of possible overtreatment.

PMID- 23559084
TI  - Hypercortisolism is associated with increased coronary arterial atherosclerosis:
      analysis of noninvasive coronary angiography using multidetector computerized
      tomography.
AB  - BACKGROUND: Observational studies show that glucocorticoid therapy and the
      endogenous hypercortisolism of Cushing's syndrome (CS) are associated with
      increased rates of cardiovascular morbidity and mortality. However, the causes of
      these findings remain largely unknown. OBJECTIVE: To determine whether CS
      patients have increased coronary atherosclerosis. DESIGN: A prospective case
      control study was performed. SETTING: Subjects were evaulated in a clinical
      research center. SUBJECTS: Fifteen consecutive patients with ACTH-dependent CS,
      14 due to an ectopic source and 1 due to pituitary Cushing's disease were
      recruited. Eleven patients were studied when hypercortisolemic; 4 patients were
      eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen
      control subjects with at least one risk factor for cardiac disease were matched
      1:1 for age, sex, and body mass index. PRIMARY OUTCOME VARIABLES: Agatston score
      a measure of calcified plaque and non-calcified coronary plaque volume were
      quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional
      variables included fasting lipids, blood pressure, history of hypertension or
      diabetes, and 24-hour urine free cortisol excretion. RESULTS: CS patients had
      significantly greater noncalcified plaque volume and Agatston score (noncalcified
      plaque volume [mm(3)] median [interquartile ranges]: CS 49.5 [31.4, 102.5],
      controls 17.9 [2.6, 25.3], P < .001; Agatston score: CS 70.6 [0, 253.1], controls
      0 [0, 7.6]; P < .05). CS patients had higher systolic and diastolic blood
      pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123,
      136], P < .02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P < .05).
      CONCLUSIONS: Increased coronary calcifications and noncalcified coronary plaque
      volumes are present in patients with active or previous hypercortisolism.
      Increased atherosclerosis may contribute to the increased rates of cardiovascular
      morbidity and mortality in patients with glucocorticoid excess.

PMID- 23559086
TI  - Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel
      oral stimulation test for the diagnosis of adult GH deficiency.
AB  - CONTEXT: In the absence of panhypopituitarism and low serum IGF-I levels, the
      diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH
      stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that
      stimulates GH secretion. OBJECTIVE: The objective of the study was to determine
      the diagnostic efficacy and safety of macimorelin in AGHD. DESIGN: This was a
      multicenter open-label study comparing the diagnostic accuracy of oral
      macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched
      controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog
      Geref Diagnostic [GHRH(1-29)NH2] became unavailable in the United States. The
      study was completed by testing 10 additional AGHD patients and 38 controls with
      macimorelin alone. MAIN OUTCOME MEASURE: Peak GH area under the receiver
      operating characteristic curve after macimorelin was measured. RESULTS: Fifty
      AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and
      controls after macimorelin were 2.36 +/- 5.69 and 17.71 +/- 19.11 ng/mL,
      respectively (P < .0001). With macimorelin, the receiver operating characteristic
      analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92%
      specificity, and 13% misclassification rate. For subjects receiving both tests,
      macimorelin showed discrimination comparable with arginine+GHRH (area under the
      receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29).
      Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak
      GH levels were inversely associated with body mass index in controls (r = -0.37,
      P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for
      obese subjects reduced the misclassification rate to 11%. Only 1 drug-related
      serious adverse event, an asymptomatic QT interval prolongation on the
      electrocardiogram, was reported. CONCLUSION: Oral macimorelin is safe,
      convenient, and effective in diagnosing AGHD with accuracy comparable with the
      arginine+GHRH test.

PMID- 23559087
TI  - Metabolically healthy but obese, a matter of time? Findings from the prospective
      Pizarra study.
AB  - BACKGROUND: Prospective longitudinal studies evaluating the relevance of
      "Metabolically Healthy but Obese" (MHO) phenotype at risk for type 2 diabetes
      mellitus (T2D) and cardiovascular diseases are few and results are contradictory.
      METHODS: As a representative of the general population, 1051 individuals were
      evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. Subjects
      without known T2D were given an oral glucose tolerance test. Anthropometric and
      biochemical variables were measured. Four sets of criteria were considered to
      define MHO subjects besides body mass index >=30 kg/m(2): A: Homeostatic Model of
      Assessment-Insulin Resistance Index (HOMA-IR) <90th percentile; B: HOMA-IR <90th
      percentile, high-density lipoprotein cholesterol >40 mg/dL in men and high
      density lipoprotein cholesterol >50 mg/dL in women, triglycerides <150 mg/dL,
      fasting glucose <110 mg/dL, and blood pressure <=140/90 mm Hg; C: HOMA-IR <90th
      percentile, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood
      pressure <=140/90 mm Hg; D: HOMA-IR <90th percentile, triglycerides <150 mg/dL,
      and fasting glucose <110 mg/dL. Subjects with T2D at baseline were excluded from
      the calculations of incidence of T2D. RESULTS: The baseline prevalence of MHO
      phenotype varied between 3.0% and 16.9%, depending on the set of criteria chosen.
      Metabolically nonhealthy obese subjects were at highest risk for becoming
      diabetic after 11 years of follow-up (odds ratio = 8.20; 95% confidence interval
      = 2.72-24.72; P < .0001). In MHO subjects the risk for becoming diabetic was
      lower than in metabolically nonhealthy obese subjects, but this risk remained
      significant (odds ratio = 3.13; 95% confidence interval = 1.07-9.17; P = .02). In
      subjects who lost weight during the study, the association between MHO phenotype
      and T2D incidence disappeared, even after adjusting for HOMA-IR. CONCLUSIONS: The
      results suggest that MHO is a dynamic concept that should be taken into account
      over time. As a clinical entity, it may be questionable.

PMID- 23559088
TI  - Optimally combining dynamical decoupling and quantum error correction.
AB  - Quantum control and fault-tolerant quantum computing (FTQC) are two of the
      cornerstones on which the hope of realizing a large-scale quantum computer is
      pinned, yet only preliminary steps have been taken towards formalizing the
      interplay between them. Here we explore this interplay using the powerful
      strategy of dynamical decoupling (DD), and show how it can be seamlessly and
      optimally integrated with FTQC. To this end we show how to find the optimal
      decoupling generator set (DGS) for various subspaces relevant to FTQC, and how to
      simultaneously decouple them. We focus on stabilizer codes, which represent the
      largest contribution to the size of the DGS, showing that the intuitive choice
      comprising the stabilizers and logical operators of the code is in fact optimal,
      i.e., minimizes a natural cost function associated with the length of DD
      sequences. Our work brings hybrid DD-FTQC schemes, and their potentially
      considerable advantages, closer to realization.

PMID- 23559090
TI  - Reply: Unusual DAT scan results.

PMID- 23559091
TI  - Depletion of histone demethylase KDM2A inhibited cell proliferation of stem cells
      from apical papilla by de-repression of p15INK4B and p27Kip1.
AB  - Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration;
      although, the molecular mechanisms of their differentiation and proliferation are
      not clearly understood, which restricts the applications of MSCs. The histone
      demethylase, lysine (K)-specific demethylase 2A (KDM2A), and the mammalian
      paralog, lysine (K)-specific demethylase 2B (KDM2B), are evolutionarily conserved
      and ubiquitously expressed members of the JmjC-domain-containing histone
      demethylase family. A previous study determined that KDM2A and KDM2B can regulate
      the differentiation of MSCs, and KDM2B has been implicated in cell cycle
      regulation by de-repressing p15(INK4B) (cyclin-dependent kinase inhibitor 2B). It
      is not known whether KDM2A is involved in the cell proliferation of MSCs. Here,
      we show that depletion of KDM2A by short hairpin RNAs can inhibit cell
      proliferation and arrest cell cycle progression at the G1/S-phase in human stem
      cells from apical papilla (SCAPs). The effect of KDM2A on cell proliferation was
      found to be mediated through de-repression of the cyclin-dependent kinase
      inhibitors, p15(INK4B) and p27(Kip1) (cyclin-dependent kinase inhibitor 1B), in
      KDM2A knock-down SCAPs. Furthermore, chromatin immunoprecipitation assays
      demonstrated that silencing of KDM2A increased histone H3 Lysine 4 (H3K4)
      trimethylation at the p15(INK4B) and p27(Kip1) loci and regulated its expression.
      Together, our results indicate that KDM2A is a H3K4 demethylase that regulates
      cell proliferation through p15(INK4B) and p27(Kip1) in SCAPs.

PMID- 23559093
TI  - A patient diagnosed with MG at onset and LEMS 20 years later.

PMID- 23559092
TI  - Small interfering RNA targeting Rac1 sensitizes colon cancer to
      dihydroartemisinin-induced cell cycle arrest and inhibited cell migration by
      suppressing NFkappaB activity.
AB  - Dihydroartemisinin (DHA) has recently shown antitumor activity in various cancer
      cells. The small GTPase Rac1 regulates many cellular processes, including
      cytoskeletal reorganization, cell migration, proliferation, and survival. In
      addition, Rac1 plays a major role in activating NFkappaB-mediated transcription.
      Both Rac1 and NFkappaB regulate many properties of the malignant phenotype,
      including anchorage-independent proliferation and survival, metastasis, and
      angiogenesis. In this study, for the first time, we demonstrated that Rac1
      knockdown can enhance DHA-induced growth inhibition, cell cycle arrest,
      apoptosis, and migration in both HCT116 and RKO cell lines in vitro. The
      mechanism is due partially to DHA, and Rac1 siRNA deactivates NFkappaB activity,
      so as to decrease tremendously the expression of its target gene products, such
      as PCNA, cyclin D1, and CDK4; and increase the expression of p21, cleaved-caspase
      3, and cleaved-PARP. In our in vivo studies, DHA also manifested remarkably
      enhanced antitumor effect when combined with Rac1 siRNA. We concluded that
      inhibition of NFkappaB activation is one of the mechanisms that Rac1 siRNA
      dramatically promotes DHAs antitumor effect on human colon cancer.

PMID- 23559094
TI  - Relation between topology and stability of bent titanocenes.
AB  - Bent metallocenes are a class of organometallic compounds that are widely used as
      catalysts in olefin polymerization procedures. We found a linear relation between
      the relative stability of bent titanocenes and the average delocalization index
      (DI) for Ti-C (from the cyclopentadienyl ring) atomic pairs within the evaluated
      compounds. As a consequence, the stability of the bent titanocenes can be
      estimated from their topologies. However, secondary interactions between the
      ligands of some of the bent titanocenes reduce the coefficient of determination
      for the average DI-stability relation. 

PMID- 23559095
TI  - Computational comparison of the kinetic stabilities of diamino- and
      diamidocarbenes in the 1,2-H shift reaction.
AB  - In this study, we performed several DFT, MP2, and BD(T) calculations on the 1,2-H
      shift reactions of two diaminocarbenes (1, 2) and a diamidocarbene (3) using the
      Gaussian 09 program. In Gaussian 09, the BD(T) method keyword requests a
      Brueckner doubles calculation including a perturbative triples contribution.
      Although N-heterocyclic carbenes (NHC) are typically known for their exceptional
      sigma-donor abilities, recent studies have indicated that pi-interactions also
      play a role in the bonding between NHCs and transition metals or BX3 (X = H, OH,
      NH2, CH3, CN, NC, F, Cl, and Br) (Nemcsok et al. Organomet 23:3640-3646, 2004,
      Esrafili. J Mol Model 18:2003-2011, 2012). In order to study the importance of pi
      interactions between carbenes and transition metals, Hobbs and co-workers (Hobbs
      et al. New J Chem 34:1295-1308, 2010) focused on the synthesis of NHCs with
      reduced-energy lowest unoccupied molecular orbitals. By introducing an oxalamide
      moiety into the heterocyclic backbone, they found the resulting carbene possessed
      higher electrophilicity than usual NHCs. According to our results, the N,N'
      diamidocarbene should be more stable than the diaminocarbenes with respect to the
      1,2-H shift reaction. 

PMID- 23559096
TI  - Tunable differential conductance of single wall C/BN nanotube heterostructure.
AB  - The transport properties and differential conductance of the heterostructures
      constructed by (5,5) single wall carbon nanotube (SWCNT) and (5,5) single wall
      boron nitride nanotube (SWBNNT) are investigated using density functional theory
      in combination with non-equilibrium Green's functions. We find that the
      transmission conductance of (5,5) BN/C nanotube heterostructure is not only
      continually depressed as the BNNT region increases but also the drop of the
      conductance is uniform in the energy window (-1.43 eV, 1 eV), which leads to
      linear I-V dependence for the systems when the bias is within this energy range.
      Moreover, the differential conductance linearly decreases when n <= 3 but
      exponentially decreases when n >= 3 for (5,5)(BN) n /C heterostructure. Such
      tunable differential conductance of (5,5) BN/C nanotube heterostructure mainly
      derives from the blockage of the transport channels induced by the semiconductive
      BN segment. 

PMID- 23559097
TI  - Theoretical design of energetic nitrogen-rich derivatives of 1,7-diamino-1,7
      dinitrimino-2,4,6-trinitro-2,4,6-triazaheptane.
AB  - The heats of formation (HOFs), energetic properties, and thermal stability of a
      series of 1,7-diamino-1,7-dinitrimino-2,4,6-trinitro-2,4,6-triazaheptane
      derivatives with different substituents, different numbers of substituents, and
      different original chains are found by using the DFT-B3LYP method. The results
      show that -NO2 or -NH2 is an effective substituent for increasing the gas-phase
      HOFs of the title compounds, especially -NO2 group. As the numbers of
      substitutents increase, their HOFs enhance obviously. Increasing the length of
      original chain is helpful for improving their HOFs. The substitution of -NO2 is
      useful for enhancing their detonation performances and the effects of the length
      of original chains on detonation properties are coupled with those of the
      substituents. An analysis of the BDE of the weakest bonds indicates that the
      substitution of the -NH2 groups and replacing the -NO2 groups of N-NO2 by the 
      NH2 groups are favorable for improving their thermal stability, while the
      substitution of -NO2 and increasing the length of original chain decrease their
      thermal stability. Considering the detonation performance and thermal stability,
      seven compounds may be considered as the potential candidates of high energy
      density compounds. 

PMID- 23559098
TI  - Hormonally responsive breast cancer cells in a microfluidic co-culture model as a
      sensor of microenvironmental activity.
AB  - Breast cancer cell growth and therapeutic response are manipulated extrinsically
      by microenvironment signals. Despite recognition of the importance of the
      microenvironment in a variety of tumor processes, predictive measures that
      incorporate the activity of the surrounding cellular environment are lacking. In
      contrast, tumor cell biomarkers are well established in the clinic. Expression of
      Estrogen Receptor-alpha (ERalpha) is the primary defining feature of hormonally
      responsive tumors and is the molecular target of therapy in the most commonly
      diagnosed molecular subtype of breast cancer. While a number of soluble factors
      have been implicated in ERalpha activation, the complexity of signaling between
      the cellular microenvironment and the cancer cell implies multivariate control.
      The cumulative impact of the microenvironment signaling, which we define as
      microenvironmental activity, is more difficult to predict than the sum of its
      parts. Here we tested the impact of an array of microenvironments on ERalpha
      signaling utilizing a microfluidic co-culture model. Quantitative
      immunofluorescence was employed to assess changes in ERalpha protein levels,
      combined with gene expression and phosphorylation status, as measures of
      activation. Analysis of microenvironment-induced growth under the same conditions
      revealed a previously undescribed correlation between growth and ERalpha protein
      down-regulation. These data suggest an expanded utility for the tumor biomarker
      ERalpha, in which the combination of dynamic regulation of ERalpha protein and
      growth in a breast cancer biosensor cell become a read-out of the
      microenvironmental activity.

PMID- 23559101
TI  - A pan-European comparison of the use of mineral trioxide aggregate (MTA) by
      postgraduates in paediatric dentistry.
AB  - AIM: To assess the current usage and opinions of mineral trioxide aggregate (MTA)
      amongst European postgraduates (PG) in paediatric dentistry. STUDY DESIGN: An on
      line structured questionnaire. METHODS: The programme directors of all EAPD
      accredited programmes in paediatric dentistry were contacted by e-mail and
      invited to disseminate the web-link for a structured on-line questionnaire to all
      PG students on their programmes. The survey sought details of usage of MTA in
      both the primary and permanent dentitions and also, previous and future
      educational requirements for cement use. RESULTS: Responses were received from
      29/44 (F: 27; M: 2) PG students. MTA was used in the primary dentition by 6/29
      and 17/29 PG for pulp capping and pulpotomy procedures, respectively. In non
      vital permanent teeth, MTA was used for apical barrier formation by 26/29 PG
      students, 15/29 for pulpotomy procedures and 10/29 to repair root perforations.
      Barriers to the use of MTA related to material cost and other materials being
      deemed more appropriate. Overall, 27/29 demonstrated an interest in further
      educational opportunities in material use. CONCLUSION: Mineral trioxide aggregate
      appears to be in regular use amongst PG dentists in paediatric dentistry
      throughout Europe.

PMID- 23559100
TI  - Identification of dominant negative effect of L522P mutation in the electrogenic
      Na+-HCO3- cotransporter NBCe1.
AB  - Homozygous mutations in the electrogenic Na(+)-HCO3 (-) cotransporter NBCe1 cause
      proximal renal tubular acidosis (pRTA) associated with extrarenal manifestations
      such as ocular abnormalities and migraine. Previously, the NBCe1 cytosolic mutant
      S982NfsX4 was shown to have a dominant negative effect by forming hetero-oligomer
      complexes with wild type (WT), which might be responsible for the occurrence of
      glaucoma and migraine in the heterozygous family members. In this study, we
      investigated whether the NBCe1 L522P mutant has a similar dominant negative
      effect. Functional analyses in Xenopus oocytes and HEK293 cells revealed that the
      L522P mutant had no transport activity due to defective membrane expression.
      Furthermore, when coexpressed with WT, L522P significantly reduced the transport
      activity of WT. In HEK293 cells, the cytosolic mutant L522P reduced the membrane
      expression of NBCe1 by forming hetero-oligomer complexes with WT. Among the
      artificial Leu(522) mutants, L522I showed proper membrane expression and normal
      transport activity. However, the other mutants L522R, L522K, L522D, and L522E
      showed a predominant cytosolic retention. Moreover, L522R had a dominant negative
      effect, when coexpressed with WT. These results indicate that Leu(522) plays an
      important role in the structure and trafficking of NBCe1. They also suggest that
      the NBCe1 mutants retaining in cytoplasm may have the dominant negative effect in
      common, which may induce some clinical manifestations.

PMID- 23559099
TI  - Sex differences in neuroadaptation to alcohol and withdrawal neurotoxicity.
AB  - Recent work suggests that sex differences exist with regard to both the nature of
      neuroadaptation to alcohol during the development of dependence, and possibly,
      the neurodegenerative consequences of alcohol dependence. Volumetric studies in
      human samples show that females may demonstrate increased volumetric brain loss
      with equal or lesser dependence histories than males. Furthermore, animal studies
      demonstrate sex differences in glutamatergic, GABAergic, and adenosinergic
      receptor signaling and endocrine responses following prolonged alcohol exposure.
      These differences may influence the development of dependence, neuronal function,
      and viability, particularly during alcohol withdrawal. The present review
      discusses the current state of knowledge in this regard. It is concluded that
      there exists a clear need for a more extensive examination of potential sex
      differences in neurodegenerative consequences of alcohol dependence in men and
      women, particularly with regard to the role that alterations in amino acid
      signaling and hypothalamic-pituitary-adrenal axis function may play. Furthermore,
      we note the need for expanded examination of the unique role that alcohol
      withdrawal-associated neuronal activity may have in the development of dependence
      associated neurotoxicity.

PMID- 23559102
TI  - Effect of minimally invasive restorations on microorganism count in the oral
      cavity of a patient with early childhood caries.
AB  - BACKGROUND: The effect of minimally invasive restorations on the microorganism
      count in the oral cavity of children with early childhood caries (ECC) has been
      only briefly discussed in the literature. CASE REPORT: This study presents the
      case of a child with ECC who was treated using a minimally invasive restorative
      approach and the patient's salivary levels of Streptococcus mutans, Lactobacillus
      spp. and Candida spp. were recorded throughout the treatment. In addition, a
      detailed discussion on the role of these microorganisms in the development of ECC
      is also presented. TREATMENT: Included minimally invasive techniques such as ART
      and removal of caries with ultrasound. The whole unstimulated saliva samples of
      the patient were inoculated in culture media for microbial count. FOLLOW-UP: A 6
      monthly review was achieved for a period of 1 year. The microbiological data were
      statistically analysed and a significant reduction (ANOVA, p < 0.05) of all
      microorganisms studied were recorded at the end of the treatment. CONCLUSION: The
      therapy used in this case and the salivary microorganism levels reported at the
      end of the treatment showed that minimally invasive restorative techniques were
      effective in controlling oral microorganisms involved in ECC.

PMID- 23559103
TI  - Effect of air abrasion and polishing on primary molar fissures.
AB  - AIM: To evaluate the effect of air abrasion and polishing on primary molar
      fissures under light microscopy. METHODS: 15 exfoliated primary second molars
      were longitudinally sectioned and photographed under a stereomicroscope (40*;
      baseline evaluation). Sections were then randomly allocated into one of the two
      groups (n = 15) and treated by either air abrasion (aluminium oxide jet) or air
      polishing (sodium bicarbonate jet) for 30 s. After treatment, sections were
      washed with an air/water spray, dried with absorbent paper, and photographed as
      previously described (final evaluation). Baseline and final morphology were
      compared by two blinded examiners who evaluated changes in the width and depth of
      fissures. STATISTICS: The percentage of changed fissures was analysed, and the
      two treatments were compared using the Mann-Whitney test (alpha = 0.01). RESULTS:
      Both air systems resulted in fissure changes in most (93.3 %) of the sections. No
      significant differences in fissure width changes were found between treatments,
      but when changes in fissure depth were evaluated, air polishing was found to be
      less damaging than air abrasion (p < 0.01). CONCLUSION: Air abrasion and
      polishing cause changes to the anatomical configuration of occlusal fissures of
      primary molars.

PMID- 23559104
TI  - Epinephrine-reduced articaine solution (1:400,000) in paediatric dentistry: a
      multicentre non-interventional clinical trial.
AB  - AIM: In paediatric dentistry, epinephrine may contribute to systemic and local
      side-effects. On the other hand it is necessary to provide good and safe local
      analgesia. Therefore, an articaine solution with reduced epinephrine
      concentration was tested in a clinical setting. METHODS: In a non-interventional
      clinical study, dental treatment was performed in children and adolescents (4-17
      years). For local analgesia, articaine 4 % plus epinephrine 1:400,000 was used in
      the technique chosen by the dentist. Efficacy and tolerance as well as duration
      of soft tissue analgesia and side-effects were evaluated. RESULTS: 999 patients
      (50.5 % male, 49.5 % female) with a mean age of 7.9 (SD 2.34) years were treated.
      Two hundred seventy six patients (27.6 %) received sedation prior to treatment.
      The mean treatment time was 15 min (SD 10). In 93.5 % of cases, initial local
      analgesia was sufficient to perform the planned treatment. In 99 % of cases (n =
      989) the planned treatment could be completed. A second injection was necessary
      in 6.5 % of cases. A mean duration of soft tissue analgesia of 2.19 h (SD 1.01)
      was seen. Slight side-effects occurred in 3.1 % of subjects. CONCLUSIONS: Due to
      high efficacy, tolerance and safety, the articaine 4 % solution with the reduced
      epinephrine concentration (1:400,000) was a safe and suitable drug for paediatric
      routine treatment.

PMID- 23559106
TI  - Water fluoridation in 40 Brazilian cities: 7 year analysis.
AB  - OBJECTIVES: Fluoride levels in the public water supplies of 40 Brazilian cities
      were analyzed and classified on the basis of risk/benefit balance. MATERIAL AND
      METHODS: Samples were collected monthly over a seven-year period from three sites
      for each water supply source. The samples were analyzed in duplicate in the
      laboratory of the Center for Research in Public Health - UNESP using an ion
      analyzer coupled to a fluoride-specific electrode. RESULTS: A total of 19,533
      samples were analyzed, of which 18,847 were artificially fluoridated and 686 were
      not artificially fluoridated. In samples from cities performing water
      fluoridation, 51.57% (n=9,720) had fluoride levels in the range of 0.55 to 0.84
      mg F/L; 30.53% (n=5,754) were below 0.55 mg F/L and 17.90% (n=3,373) were above
      0.84 mg F/L (maximum concentration=6.96 mg F/L). Most of the cities performing
      fluoridation that had a majority of samples with fluoride levels above the
      recommended parameter had deep wells and more than one source of water supply.
      There was some variability in the fluoride levels of samples from the same site
      and between collection sites in the same city. CONCLUSIONS: The majority of
      samples from cities performing fluoridation had fluoride levels within the range
      that provides the best combination of risks and benefits, minimizing the risk of
      dental fluorosis while preventing dental caries. The conduction of studies about
      water distribution systems is suggested in cities with high natural fluoride
      concentrations in order to optimize the use of natural fluoride for fluoridation
      costs and avoid the risk of dental fluorosis.

PMID- 23559105
TI  - Periodontal disease and diabetes mellitus.
AB  - Periodontal disease (PD) is one of the most commonly known human chronic
      disorders. The relationship between PD and several systemic diseases such as
      diabetes mellitus (DM) has been increasingly recognized over the past decades.
      OBJECTIVE: The purpose of this review is to provide the reader with knowledge
      concerning the relationship between PD and DM. Many articles have been published
      in the English and Portuguese literature over the last 50 years examining the
      relationship between these two chronic diseases. Data interpretation is often
      confounded by varying definitions of DM, PD and different clinical criteria were
      applied to determine the prevalence, extent and severity of PD, levels of
      glycemic control and diabetes-related complications. METHODS: This paper provides
      a broad overview of the predominant findings from research conducted using the
      BBO (Bibliografia Brasileira de Odontologia), MEDLINE, LILACS and PubMed for
      Controlled Trials databases, in English and Portuguese languages published from
      1960 to October 2012. Primary research reports on investigations of relationships
      between DM/DM control, PD/periodontal treatment and PD/DM/diabetes-related
      complications identified relevant papers and meta-analyses published in this
      period. RESULTS: This paper describes the relationship between PD and DM and
      answers the following questions: 1- The effect of DM on PD, 2- The effects of
      glycemic control on PD and 3- The effects of PD on glycemic control and on
      diabetes-related complications. CONCLUSIONS: The scientific evidence reviewed
      supports diabetes having an adverse effect on periodontal health and PD having an
      adverse effect on glycemic control and on diabetes-related complications. Further
      research is needed to clarify these relationships and larger, prospective,
      controlled trials with ethnically diverse populations are warranted to establish
      that treating PD can positively influence glycemic control and possibly reduce
      the burden of diabetes-related complications.

PMID- 23559107
TI  - Mechanical testing of thin-walled zirconia abutments.
AB  - Although the use of zirconia abutments for implant-supported restorations has
      gained momentum with the increasing demand for esthetics, little informed design
      rationale has been developed to characterize their fatigue behavior under
      different clinical scenarios. However, to prevent the zirconia from fracturing,
      the use of a titanium connection in bi-component aesthetic abutments has been
      suggested. OBJECTIVE: Mechanical testing of customized thin-walled titanium
      zirconia abutments at the connection with the implant was performed in order to
      characterize the fatigue behavior and the failure modes for straight and angled
      abutments. MATERIAL AND METHODS: Twenty custom-made bi-component abutments were
      tested according to ISO 14801:2007 either at a straight or a 25 degrees  angle
      inclination (n=10 each group). Fatigue was conducted at 15 Hz for 5 million
      cycles in dry conditions at 20 degrees C+/-5 degrees C. Mean values and standard
      deviations were calculated for each group. All comparisons were performed by t
      tests assuming unequal variances. The level of statistical significance was set
      at p<=0.05. Failed samples were inspected in a polarized-light and then in a
      scanning electron microscope. RESULTS: Straight and angled abutments mean maximum
      load was 296.7 N and 1,145 N, the dynamic loading mean Fmax was 237.4 N and 240.7
      N, respectively. No significant differences resulted between the straight and
      angled bi-component abutments in both static (p=0.253) and dynamic testing
      (p=0.135). A significant difference in the bending moment required for fracture
      was detected between the groups (p=0.01). Fractures in the angled group occurred
      mainly at the point of load application, whereas in the straight abutments,
      fractures were located coronally and close to the thinly designed areas at the
      cervical region. CONCLUSION: Angled or straight thin-walled zirconia abutments
      presented similar Fmax under fatigue testing despite the different bending
      moments required for fracture. The main implication is that although zirconia
      angled or straight abutments presented similar mechanical behavior, the failure
      mode tended to be more catastrophic in straight (fracture at the cervical region)
      compared to angled abutments.

PMID- 23559108
TI  - Effect of Zingiber officinale and propolis on microorganisms and endotoxins in
      root canals.
AB  - The purpose of this study was to evaluate the effectiveness of glycolic propolis
      (PRO) and ginger (GIN) extracts, calcium hydroxide (CH), chlorhexidine (CLX) gel
      and their combinations as ICMs (ICMs) against Candida albicans, Enterococcus
      faecalis, Escherichia coli and endotoxins in root canals. MATERIAL AND METHODS:
      After 28 days of contamination with microorganisms, the canals were instrumented
      and then divided according to the ICM: CH+saline; CLX, CH+CLX, PRO, PRO+CH; GIN;
      GIN+CH; saline. The antimicrobial activity and quantification of endotoxins by
      the chromogenic test of Limulus amebocyte lysate were evaluated after
      contamination and instrumentation at 14 days of ICM application and 7 days after
      ICM removal. RESULTS AND CONCLUSION: After analysis of results and application of
      the Kruskal-Wallis and Dunn statistical tests at 5% significance level, it was
      concluded that all ICMs were able to eliminate the microorganisms in the root
      canals and reduce their amount of endotoxins; however, CH was more effective in
      neutralizing endotoxins and less effective against C. albicans and E. faecalis,
      requiring the use of medication combinations to obtain higher success.

PMID- 23559109
TI  - Biocompatibility and setting time of CPM-MTA and white Portland cement clinker
      with or without calcium sulfate.
AB  - OBJECTIVE: To evaluate the biocompatibility and the setting time of Portland
      cement clinker with or without 2% or 5% calcium sulfate and MTA-CPM. MATERIAL AND
      METHODS: Twenty-four mice (Rattus norvegicus) received subcutaneously
      polyethylene tubes filled with Portland cement clinker with or without 2% or 5%
      calcium sulfate and MTA. After 15, 30 and 60 days of implantation, the animals
      were killed and specimens were prepared for microscopic analysis. For evaluation
      of the setting time, each material was analyzed using Gilmore needles weighing
      113.5 g and 456.5 g, according to the ASTM specification Number C266-08
      guideline. Data were analyzed by ANOVA and Tukey's test for setting time and
      Kruskal-Wallis and Dunn test for biocompatibility at 5% significance level.
      RESULTS: Histologic observation showed no statistically significant difference of
      biocompatibility (p>0.05) among the materials in the subcutaneous tissues. For
      the setting time, clinker without calcium sulfate showed the shortest initial and
      final setting times (6.18 s/21.48 s), followed by clinker with 2% calcium sulfate
      (9.22 s/25.33 s), clinker with 5% calcium sulfate (10.06 s/42.46 s) and MTA
      (15.01 s/42.46 s). CONCLUSIONS: All the tested materials showed biocompatibility
      and the calcium sulfate absence shortened the initial and final setting times of
      the white Portland cement clinker.

PMID- 23559110
TI  - Synthesis and cytotoxicity evaluation of granular magnesium substituted beta
      tricalcium phosphate.
AB  - OBJECTIVE: The aim of this study was to produce dense granules of tricalcium
      phosphate (beta-TCP) and magnesium (Mg) substituted beta-TCP, also known as beta
      TCMP (Mg/Ca=0.15 mol), in order to evaluate the impact of Mg incorporation on the
      physicochemical parameters and in vitro biocompatibility of this novel material.
      MATERIAL AND METHODS: The materials were characterized using X-ray diffraction
      (XRD), infrared spectroscopy (FTIR), electron microscopy and inductively coupled
      plasma (ICP). Biocompatibility was assayed according to ISO 10993-12:2007 and
      7405:2008, by two different tests of cell survival and integrity (XTT and CVDE).
      RESULTS: The XRD profile presented the main peaks of beta-TCP (JCPDS 090169) and
      beta-TCMP (JCPDS 130404). The characteristic absorption bands of TCP were also
      identified by FTIR. The ICP results of beta-TCMP granules extract showed a
      precipitation of calcium and release of Mg into the culture medium. Regarding the
      cytotoxicity assays, beta-TCMP dense granules did not significantly affect the
      mitochondrial activity and relative cell density in relation to beta-TCP dense
      granules, despite the release of Mg from granules into the cell culture medium.
      CONCLUSION: beta-TCMP granules were successfully produced and were able to
      release Mg into media without cytotoxicity, indicating the suitability of this
      promising material for further biological studies on its adequacy for bone
      therapy.

PMID- 23559111
TI  - Long-term cytotoxic effects of contemporary root canal sealers.
AB  - OBJECTIVES: The aim of the present study was to investigate the effects of root
      canal sealers on the cytotoxicity of 3T3 fibroblasts during a period of 5 weeks.
      MATERIAL AND METHODS: Fibroblasts (3T3, 1*105 cells per well) were incubated with
      elutes of fresh specimens from eight root canal sealers (AH Plus, Epiphany,
      Endomethasone N, EndoREZ, MTA Fillapex, Pulp Canal Sealer EWT, RoekoSeal and
      Sealapex) and with elutes of the same specimens for 5 succeeding weeks after
      immersing in simulated body fluid. The cytotoxicity of all root canal sealers was
      determined using the MTT assay. Data were analyzed using ANOVA and Tukey's test.
      RESULTS: RoekoSeal was the only sealer that did not show any cytotoxic effects
      (p<0.05). All the other tested sealers exhibited severe toxicity initially (week
      0). MTA Fillapex remained moderately cytotoxic after the end of experimental
      period. Toxicity of the other tested sealers decreased gradually over time. The
      evaluated root canal sealers presented varying degrees of cytotoxicity, mainly in
      fresh mode. CONCLUSIONS: RoekoSeal had no cytotoxic effect both freshly mixed and
      in the other tested time points. MTA Fillapex was associated with significantly
      less cell viability when compared to the other tested root canal sealers.

PMID- 23559112
TI  - Polyspecies biofilm formation on implant surfaces with different surface
      characteristics.
AB  - OBJECTIVE: To investigate the microbial adherence and colonization of a
      polyspecies biofilm on 7 differently processed titanium surfaces. MATERIAL AND
      METHODS: Six-species biofilms were formed anaerobically on 5-mm-diameter
      sterilized, saliva-preconditioned titanium discs. Material surfaces used were
      either machined, stained, acid-etched or sandblasted/acid-etched (SLA). Samples
      of the latter two materials were also provided in a chemically modified form,
      with increased wettability characteristics. Surface roughness and contact angles
      of all materials were determined. The discs were then incubated anaerobically for
      up to 16.5 h. Initial microbial adherence was evaluated after 20 min incubation
      and further colonization after 2, 4, 8, and 16.5 h using non-selective and
      selective culture techniques. Results at different time points were compared
      using ANOVA and Scheffe post hoc analysis. RESULTS: The mean differences in
      microorganisms colonizing after the first 20 min were in a very narrow range (4.5
      to 4.8 log CFU). At up to 16.5 h, the modified SLA surface exhibited the highest
      values for colonization (6.9+/-0.2 log CFU, p<0.05) but increasing growth was
      observed on all test surfaces over time. Discrepancies among bacterial strains on
      the differently crafted titanium surfaces were very similar to those described
      for total log CFU. F. nucleatum was below the detection limit on all surfaces
      after 4 h. CONCLUSION: Within the limitations of this in vitro study, surface
      roughness had a moderate influence on biofilm formation, while wettability did
      not seem to influence biofilm formation under the experimental conditions
      described. The modified SLA surface showed the highest trend for bacterial
      colonization.

PMID- 23559113
TI  - Effect of phosphoric acid etching on the shear bond strength of two self-etch
      adhesives.
AB  - OBJECTIVE: To evaluate the effect of optional phosphoric acid etching on the
      shear bond strength (SBS) of two self-etch adhesives to enamel and dentin.
      MATERIAL AND METHODS: Ninety-six bovine mandibular incisors were ground flat to
      obtain enamel and dentin substrates. A two-step self-etch adhesive (FL-Bond II)
      and a one-step self-etch adhesive (BeautiBond) were applied with and without a
      preliminary acid etching to both the enamel and dentin. The specimens were
      equally and randomly assigned to 4 groups per substrate (n=12) as follows: FL
      Bond II etched; FL-Bond II un-etched; BeautiBond etched; BeautiBond un-etched.
      Composite cylinders (Filtek Z100) were bonded onto the treated tooth structure.
      The shear bond strength was evaluated after 24 hours of storage (37 degrees C,
      100% humidity) with a testing machine (Ultra-tester) at a speed of 1 mm/min. The
      data was analyzed using a two-way ANOVA and post-hoc Tukey's test with a
      significance level of p<0.05. A field emission scanning electron microscope was
      used for the failure mode analysis. RESULTS: Both adhesives evidenced a
      significant decrease in the dentin SBS with the use of an optional phosphoric
      acid-etching step (p<0.05). Preliminary phosphoric acid etching yielded
      significantly higher enamel SBS for FL-Bond II (p<0.05) only, but not for
      BeautiBond. FL-Bond II applied to un-etched dentin demonstrated the highest mean
      bond strength (37.7+/-3.2 MPa) and BeautiBond applied to etched dentin showed the
      lowest mean bond strength (18.3+/-6.7 MPa) among all tested groups (p<0.05).
      CONCLUSION: The use of a preliminary acid-etching step with 37.5% phosphoric acid
      had a significant adverse effect on the dentin bond strength of the self-etch
      adhesives evaluated while providing improvement on the enamel bond strength only
      for FL-Bond II. This suggests that the potential benefit that may be derived from
      an additional etching step with phosphoric acid does not justify the risk of
      adversely affecting the bond strength to dentin.

PMID- 23559114
TI  - Chemical treatment of the intra-canal dentin surface: a new approach to modify
      dentin hydrophobicity.
AB  - OBJECTIVE: This study evaluated the hydrophobicity of dentin surfaces that were
      modified through chemical silanization with octadecyltrichlorosilane (OTS).
      MATERIAL AND METHODS: An in vitro experimental study was performed using 40 human
      permanent incisors that were divided into the following two groups: non-silanized
      and silanized. The specimens were pretreated and chemically modified with OTS.
      After the chemical modification, the dentin hydrophobicity was examined using a
      water contact angle measurement (WCA). The effectiveness of the modification of
      hydrophobicity was verified by the fluid permeability test (FPT). RESULTS AND
      CONCLUSIONS: Statistically significant differences were found in the values of
      WCA and FPT between the two groups. After silanization, the hydrophobic
      intraradicular dentin surface exhibited in vitro properties that limit fluid
      penetration into the sealed root canal. This chemical treatment is a new approach
      for improving the sealing of the root canal system.

PMID- 23559115
TI  - Marginal adaptation of class V composite restorations submitted to thermal and
      mechanical cycling.
AB  - OBJECTIVE: This study evaluated the effect of the margin location and an adhesive
      system on the marginal adaptation of composite restorations. MATERIAL AND
      METHODS: Class V cavities were prepared in bovine teeth with the gingival margin
      on the dentin and the incisal margin on the enamel. The cavities were restored
      with a micro-hybrid composite resin using an etch-and-rinse [Single Bond 2 (SB)]
      or a self-etching adhesive [Clearfil SE Bond (CL)]. After finishing and polishing
      the restorations, epoxy replicas were prepared. The marginal adaptation was
      analyzed using scanning electronic microscopy (SEM, 500 x magnification). The
      higher gap width in each margin was recorded (T0). After the first evaluation,
      the samples were submitted to thermal cycling (2,000 cycles of 5 degrees C+/-2
      degrees C followed by 55 degrees C+/-2 degrees C - T1) and mechanical cycling
      (100,000 cycles of 50 kN and 2 Hz - T2). Replicas of samples were rebuilt after
      each cycling and analyzed under SEM. The data were submitted to Mann-Whitney,
      Wilcoxon and Friedman testing (alpha=0.05). RESULTS: The SB presented higher gaps
      in the dentin than the enamel, while there was no difference between the
      substrate for the CL. In the dentin, the CL showed better marginal sealing than
      the SB. The opposite occurred in the enamel. There were no significant
      differences between the baseline, thermal and mechanical cycling for any
      experimental condition. CONCLUSIONS: The outcomes of the present study showed
      that the adhesive system and margin location have an important effect on the
      marginal adaptation of composite restorations.

PMID- 23559116
TI  - Ex vivo microbial leakage after using different final irrigation regimens with
      chlorhexidine.
AB  - OBJECTIVE: To assess the influence of final irrigation protocols with
      chlorhexidine in the coronal leakage of Enterococcus faecalis in filled root
      canals. MATERIAL AND METHODS: Seventy single-root canals from extracted teeth
      were prepared using ProTaper instruments. The irrigation protocol accomplished an
      alternating irrigation with 5 mL of 2.5% sodium hypochlorite (NaOCI) and 17% EDTA
      between each file. The teeth were randomly divided into four experimental groups
      (n=15) according to the final irrigation regimen: group 1, without final
      irrigation; group 2, irrigation with 10 mL 2.0% chlorhexidine (CHX); group 3,
      with a final application of EC40TM; and group 4, irrigation with the combination
      (1:1) of 0.2% CHX + 0.1% cetrimide (CTR). All the teeth were mounted in a two
      chamber apparatus and the coronal access was exposed to E. faecalis. The presence
      of turbidity in the BHI broth over a period of 180 days was observed. The
      Friedman test was used for statistical analysis. RESULTS: EC40TM varnish showed
      the least leakage at 180 days, and was statistically similar to 2% CHX. No
      significant differences were observed between the group without final irrigation
      and the 2% CHX group or 0.2% CHX + 0.1% CTR. CONCLUSIONS: In this ex vivo study,
      EC40TM showed the longest delayed coronal leakage of E. faecalis, although
      without significant differences from 2% CHX.

PMID- 23559117
TI  - Six-month evaluation of a resin/dentin interface created by methacrylate and
      silorane-based materials.
AB  - OBJECTIVES: This study aimed to compare the micro-tensile bond strength of
      methacrylate resin systems to a silorane-based restorative system on dentin after
      24 hours and six months water storage. MATERIAL AND METHODS: The restorative
      systems Adper Single Bond 2/Filtek Z350 (ASB), Clearfil SE Bond/Z350 (CF), Adper
      SE Plus/Z350 (ASEP) and P90 Adhesive System/Filtek P90 (P90) were applied on flat
      dentin surfaces of 20 third molars (n=5). The restored teeth were sectioned
      perpendicularly to the bonding interface to obtain sticks (0.8 mm2) to be tested
      after 24 hours (24 h) and 6 months (6 m) of water storage, in a universal testing
      machine at 0.5 mm/min. The data was analyzed via two-way Analysis of
      Variance/Bonferroni post hoc tests at 5% global significance. RESULTS: Overall
      outcomes did not indicate a statistical difference for the resin systems (p=0.26)
      nor time (p=0.62). No interaction between material * time was detected (p=0.28).
      Mean standard-deviation in MPa at 24 h and 6 m were: ASB 31.38 (4.53) and 30.06
      (1.95), CF 34.26 (3.47) and 32.75 (4.18), ASEP 29.54 (4.14) and 33.47 (2.47), P90
      30.27 (2.03) and 31.34 (2.19). CONCLUSIONS: The silorane-based system showed a
      similar performance to methacrylate-based materials on dentin. All systems were
      stable in terms of bond strength up to 6 month of water storage.

PMID- 23559118
TI  - Do blood contamination and haemostatic agents affect microtensile bond strength
      of dual cured resin cement to dentin?
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of blood
      contamination and haemostatic agents such as Ankaferd Blood Stopper (ABS) and
      hydrogen peroxide (H2O2) on the microtensile bond strength between dual cured
      resin cement-dentin interface. MATERIAL AND METHODS: Twelve pressed lithium
      disilicate glass ceramics were luted to flat occlusal dentin surfaces with
      Panavia F under the following conditions: CONTROL GROUP: no contamination, Group
      Blood: blood contamination, Group ABS: ABS contamination Group H2O2: H2O2
      contamination. The specimens were sectioned to the beams and microtensile testing
      was carried out. Failure modes were classified under stereomicroscope. Two
      specimens were randomly selected from each group, and SEM analyses were
      performed. RESULTS: There were significant differences in microtensile bond
      strengths (uTBS) between the control and blood-contaminated groups (p<0.05),
      whereas there were no significant differences found between the control and the
      other groups (p>0.05). CONCLUSIONS: Contamination by blood of dentin surface
      prior to bonding reduced the bond strength between resin cement and the dentin.
      Ankaferd Blood Stoper and H2O2 could be used safely as blood stopping agents
      during cementation of all-ceramics to dentin to prevent bond failure due to blood
      contamination.

PMID- 23559120
TI  - The Journal of Applied Oral Science and the open science era.

PMID- 23559119
TI  - Seven years of external control of fluoride levels in the public water supply in
      Bauru, Sao Paulo, Brazil.
AB  - Fluoridation of the public water supplies is recognized as among the top ten
      public health achievements of the twentieth century. However, the positive
      aspects of this measure depend on the maintenance of fluoride concentrations
      within adequate levels. OBJECTIVE: To report the results of seven years of
      external control of the fluoride (F) concentrations in the public water supply in
      Bauru, SP, Brazil in an attempt to verify, on the basis of risk/benefit balance,
      whether the levels are appropriate. MATERIAL AND METHODS: From March 2004 to
      February 2011, 60 samples were collected every month from the 19 supply sectors
      of the city, totaling 4,641 samples. F concentrations in water samples were
      determined in duplicate, using an ion-specific electrode (Orion 9609) coupled to
      a potentiometer after buffering with TISAB II. After the analysis, the samples
      were classified according to the best risk-benefit adjustment. RESULTS: Means (+/
      standard deviation) of F concentrations ranged between 0.73+/-0.06 and 0.81+/
      0.10 mg/L for the different sectors during the seven years. The individual values
      ranged between 0.03 and 2.63 mg/L. The percentages of the samples considered "low
      risk" for dental fluorosis development and of "maximum benefit" for dental caries
      prevention (0.55-0.84 mg F/L) in the first, second, third, fourth, fifth, sixth,
      and seventh years of the study were 82.0, 58.5, 37.4, 61.0, 89.9, 77.3, and
      72.4%, respectively, and 69.0% for the entire period. CONCLUSIONS: Fluctuations
      of F levels were found in the public water supply in Bauru during the seven years
      of evaluation. These results suggest that external monitoring of water
      fluoridation by an independent assessor should be implemented in cities where
      there is adjusted fluoridation. This measure should be continued in order to
      verify that fluoride levels are suitable and, if not, to provide support for the
      appropriate adjustments.

PMID- 23559121
TI  - Muscle-damaging exercise increases heat strain during subsequent exercise heat
      stress.
AB  - PURPOSE: It remains unclear whether exercise-induced muscle damage (EIMD)
      increases heat strain during subsequent exercise heat stress, which in turn may
      increase the risk of exertional heat illness. We examined heat strain during
      exercise heat stress 30 min after EIMD to coincide with increases in circulating
      pyrogens (e.g., interleukin-6 [IL-6]) and 24 h after EIMD to coincide with the
      delayed muscle inflammatory response when a higher rate of metabolic energy
      expenditure (M) and thus decreased economy might also increase heat strain.
      METHODS: Thirteen non-heat-acclimated males (mean +/- SD, age = 20 +/- 2 yr)
      performed exercise heat stress tests (running for 40 min at 65% VO2max in 33
      degrees C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment, involving
      running for 60 min at 65% VO2max on either -10% gradient (EIMD) or +1% gradient
      (CON) in a crossover design. Rectal (Tre) and skin (Tsk) temperature, local
      sweating rate, and M were measured throughout HS tests. RESULTS: Compared with
      CON, EIMD evoked higher circulating IL-6 pre-HS1 (P < 0.01) and greater plasma
      creatine kinase and muscle soreness pre-HS2 (P < 0.01). The DeltaTre was greater
      after EIMD than CON during HS1 (0.35 degrees C, 95% confidence interval = 0.11
      degrees C-0.58 degrees C, P < 0.01) and HS2 (0.17 degrees C, 95% confidence
      interval = 0.07 degrees C-0.28 degrees C, P < 0.01). M was higher on EIMD
      throughout HS1 and HS2 (P < 0.001). Thermoeffector responses (Tsk, sweating rate)
      were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25
      min during HS1 (P < 0.05). The final Tre during HS1 correlated with the pre-HS1
      circulating IL-6 concentration (r = 0.67). CONCLUSIONS: Heat strain was increased
      during endurance exercise in the heat conducted 30 min after and, to a much
      lesser extent, 24 h after muscle-damaging exercise. These data indicate that EIMD
      is a likely risk factor for exertional heat illness particularly during exercise
      heat stress when behavioral thermoregulation cues are ignored.

PMID- 23559122
TI  - Prior exercise and postprandial incretin responses in lean and obese individuals.
AB  - PURPOSE: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP) help regulate postprandial
      triacylglycerol (TAG) and insulin concentrations, but the effects of acute
      aerobic exercise on GLP-1 or GIP responses are unclear. The purpose of this study
      was to determine whether reductions in postprandial TAG and insulin with exercise
      are associated with GLP-1 and GIP responses. METHODS: Thirteen normal-weight (NW)
      and 13 obese (Ob) individuals participated in two, 4-d trials in random order
      including an exercise (EX) and a no exercise (NoEX) trial. Diet was controlled
      during both trials. The EX trial consisted of 1 h of treadmill walking (55%-60%
      of VO2peak) during the evening of day 3 of the trial, 12 h before a 4-h mixed
      meal test on day 4, during which frequent blood samples were collected to assess
      postprandial lipemia, glycemia, insulin, C-peptide, GIP, and GLP-1 responses.
      Insulin secretion was estimated using the insulinogenic index, and insulin
      clearance was estimated using the ratio of insulin to C-peptide. RESULTS:
      Postprandial TAG were 29% lower after EX in Ob individuals (P < 0.05) but were
      not significantly altered in NW individuals (P > 0.05). The drop in postprandial
      HDL cholesterol was attenuated with EX in Ob individuals (P < 0.05). Insulin
      responses were 14% lower after EX in Ob individuals (P < 0.05), and this was
      associated with reduced insulin secretion (P < 0.05), with no change in insulin
      clearance (P > 0.05). Glucose, C-peptide, GIP, and GLP-1 were not different
      between trials. CONCLUSION: A 1-h bout of moderate-intensity aerobic exercise the
      night before a mixed meal attenuates TAG and insulin responses in Ob but not NW
      individuals, an effect not associated with altered GLP-1 or GIP responses.

PMID- 23559123
TI  - Athletic participation in children with symptomatic spondylolysis in the New York
      area.
AB  - PURPOSE: The purpose of this study was to assess athletic activities associated
      with spondylolysis in children and adolescents in a New York metropolitan
      tertiary referral center. METHODS: We retrospectively evaluated 137 consecutive
      cases of symptomatic spondylolysis presenting to one of two pediatric orthopedic
      spine surgeons. Ten patients who did not participate in any organized athletics
      were excluded, leaving 127 children for analysis. Data regarding spondylolysis
      and athletic participation were gathered for analysis. RESULTS: One hundred and
      twenty-seven patients were analyzed (mean age, 13.9 +/- 2.2 yr). All patients had
      initial x-rays, with nearly all obtaining further advanced level imaging to
      confirm the diagnosis of spondylolysis. Magnetic resonance imaging was obtained
      in 42.5% of cases, limited computed tomography scan in 29.1% of cases, and single
      photon emission computed tomography scan in 23.6% of cases. The most common
      location of spondylolysis was at the L5 level (74%), of which 43.6% were
      bilateral. Of the overall cohort, 2.4% had spondylolysis at multiple levels. The
      most common athletic activities associated with spondylolysis in this cohort were
      soccer (19.3%), basketball (17.2%), and lacrosse (9.4%). CONCLUSION: Although
      previous reports have implicated participation in various sports in the
      development of symptomatic spondylolysis in children, lacrosse and baseball have
      rarely been associated with spondylolysis. We found that in the New York
      metropolitan area, soccer, basketball, lacrosse, baseball, tennis, and football
      were most commonly associated with spondylolysis. Therefore, we emphasize
      consideration of spondylolysis in these children if they present with low back
      pain. These results may be used to counsel parents and young athletes about the
      possibility of spondylolysis as an etiology of lumbar back pain and in educating
      coaches, teachers, school nurses, and primary care providers.

PMID- 23559124
TI  - Effect of salbutamol on neuromuscular function in endurance athletes.
AB  - PURPOSE: The potential ergogenic effects of therapeutic inhaled salbutamol doses
      in endurance athletes have been controversially discussed for decades. We
      hypothesized that salbutamol inhalation may increase peripheral muscle
      contractility, reduce fatigability, and improve force recovery after a localized
      exercise in endurance athletes. METHODS: Eleven healthy, nonasthmatic male
      athletes with high aerobic capacities were recruited to be compared in a double
      blinded, randomized crossover study of two dose levels of salbutamol (200 and 800
      MUg) and a placebo administered by inhalation before a quadriceps fatigue test.
      Subjects performed an incremental exercise protocol consisting in sets of 10
      intermittent isometric contractions starting at 20% of maximum voluntary
      contraction (MVC) with 10% MVC increment until exhaustion. Femoral nerve magnetic
      stimulation was used during and after MVC to evaluate neuromuscular fatigue after
      each set, at task failure, and after 10 and 30 min of recovery. RESULTS: Initial
      MVC and evoked muscular responses were not modified with salbutamol (P > 0.05).
      The total number of submaximal contractions until task failure significantly
      differed between treatments (placebo, 72 +/- 7; 200 ug, 78 +/- 8; and 800 ug, 82
      +/- 7; P < 0.01). MVC and evoked muscular responses were similarly reduced with
      all treatments during the fatiguing task (all P > 0.05). Voluntary activation was
      unaffected by the fatiguing task and treatments (P > 0.05). CONCLUSION:
      Supratherapeutic inhaled doses of beta2-agonists increased quadriceps endurance
      during an incremental and localized fatiguing task in healthy endurance-trained
      athletes without significant effect on neuromuscular fatigue. Further studies are
      needed to clarify the underlying mechanisms.

PMID- 23559125
TI  - Immunological rejection following allogeneic cultivated limbal epithelial
      transplantation.

PMID- 23559127
TI  - [Cystoscopy in non-muscle-invasive bladder cancer: when and how (rigid or
      flexible)].
AB  - Cystoscopy is a common procedure in the urological practice due to its ability to
      survey the bladder for a variety of indications. It is the principal means of
      diagnosis and surveillance of bladder tumors. Hematuria is the most common
      finding of non-muscle-invasive bladder cancer (NMIBC), as a consequence of that
      it is one of the most frequent reasons to perform cystoscopy. The follow-up of
      patients treated for NMIBC is of great importance because of the high incidence
      of recurrence and progression of the disease, whereby patients with NMIBC undergo
      cystoscopy repeatedly (every three months generally). At present, the schedule
      and methods of follow-up is a sign of patient's progression and recurrence risk,
      which has to be rated for each patient when follow-up begins. Moreover, before
      the development of flexible cystoscopy, patients underwent rigid cystoscopy with
      greater discomfort. The advance of flexible cystoscopy has significantly
      decreased the pain and discomfort associated with the procedure, and the flexible
      instrument is currently considered the standard tool to perform cystoscopy.
      However, controversies exist about the use of anesthetic gel during cystoscopy.
      The aim of this study is to report some short evidence about cystoscopy in
      particularly about the follow-up timing for NMIBC and the use of rigid or
      flexible cystoscopy.

PMID- 23559126
TI  - Glyceollins, a novel class of soybean phytoalexins, inhibit SCF-induced
      melanogenesis through attenuation of SCF/c-kit downstream signaling pathways.
AB  - The anti-melanogenesis effect of glyceollins was examined by melanin synthesis,
      tyrosinase activity assay in zebrafish embryos and in B16F10 melanoma cells. When
      developing zebrafish embryos were treated with glyceollins, pigmentation of the
      embryos, melanin synthesis and tyrosinase activity were all decreased compared
      with control zebrafish embryos. In situ expression of a pigment cell-specific
      gene, Sox10, was dramatically decreased by glyceollin treatment in the neural
      tubes of the trunk region of the embryos. Stem cell factor (SCF)/c-kit signaling
      pathways as well as expression of microphthalmia-associated transcription factor
      (MITF) were determined by western blot analysis. Glyceollins inhibited melanin
      synthesis, as well as the expression and activity of tyrosinase induced by SCF,
      in a dose-dependent manner in B16F10 melanoma cells. Pretreatment of B16F10 cells
      with glyceollins dose-dependently inhibited SCF-induced c-kit and Akt
      phosphorylation. Glyceollins significantly impaired the expression and activity
      of MITF. An additional inhibitory function of glyceollins was to effectively
      downregulate intracellular cyclic AMP levels stimulated by SCF in B16F10 cells.
      Glyceollins have a depigmentation/whitening activity in vitro and in vivo, and
      that this effect may be due to the inhibition of SCF-induced c-kit and tyrosinase
      activity through the blockade of downstream signaling pathway.

PMID- 23559128
TI  - [Epidemiology of disease conditions in Italy. Has anything changed? Environment,
      professional exposure, and lifestyle. Is time for screening?].
AB  - Risk factors analysis in bladder cancer should consider not only the clinical and
      pathological features of the tumor but also environmental and lifestyle factors.
      They may play, in fact, a relevant role not only in the pathogenesis but also in
      the biological behavior of the tumor. The association between cigarette smoking
      and bladder cancer has been consistently confirmed in several case-control and
      cohort studies. The risk of bladder cancer seems to increase with duration and
      intensity of smoking. Another environmental risk factor, although not
      definitively proved, is water supply. Chlorination or water pollution by
      pesticides and other chemical factors is considered a relevant risk factor.
      Familiarity and genetic predisposition, diet and individual risk factors should
      be taken into account.

PMID- 23559129
TI  - [Therapeutic strategies in penile cancer: state of the art].
AB  - A systematic review of the current treatment options and of the outcomes of
      penile carcinoma has been performed with special focus on controversial issues. A
      MedLine search using specified search terms was done during the period 1988 -
      January 2013. Demolitive surgery is considered as the "gold standard" treatment
      of invasive penile carcinoma staged higher than T2, but negative psychological
      outcomes were reported. On the other hand, conservative surgical techniques have
      been associated with higher recurrence rates. Potency-sparing technique
      (glansectomy and apexes sparing) preserves penile length: the reconstruction of
      glans anatomy and function is a key point to restore anatomy and sexual
      functions. Techniques such as glanduloplasty have given satisfactory anatomic,
      functional and sexual outcomes. Lymphadenectomy is indicated in any case of
      inguinal palpable nodes that persist after a course of antibiotic therapy, but
      also in all the cases staged T2 or higher, or in any high-grade penile cancer. It
      is still being debated the extension of inguinal lymphadenectomy for penile
      cancer: unilateral, bilateral, and extended to pelvic lymph nodes. Due to the
      specific radioresistance of penile cancer, radiation therapy is currently
      indicated in case of unresectable penile cancers with palliative intent.
      Chemotherapy is indicated as adjuvant therapy for stage T1-T3, N1-3, M0, or as
      neo-adjuvant therapy in the event of extensive pelvic and inguinal
      lymphadenopathies, or as palliative treatment in patients with unresectable or
      metastatic cancers. New chemotherapy agents such as Cis - platinum and Taxanes
      have shown promising results in early trials.

PMID- 23559130
TI  - [Safety notice for the use of drugs for intravesical instillations and cost
      analysis].
AB  - Among the objectives outlined in the National Health Plan 1998-2000 are some
      interventions to improve the safety of public and private health-care facilities.
      One of the significant risks in the health sector is the one resulting from
      exposure to chemotherapy drugs. The Health Surveillance must take into account
      that anticancer drugs are cytotoxic compounds, which can cause cancer. It is
      necessary that occupational exposure to antineoplastic agents be kept within the
      lowest possible level. The potential absorption due to exposure to chemotherapy
      may be significantly reduced by adopting preventive measures specific to
      particular concern in a centralization of structures and activities. To ensure an
      adequate system of protection for people who use these substances in professional
      health-care settings, there should be the establishment of a specific "Anticancer
      Drugs Unit" to entrust the working cycle. The places reserved for the preparation
      of cytotoxic chemotherapy must be equipped with floor and walls up to heights of
      appropriate plastic material easily washable. Inside the room there must be a
      "point of decontamination" for washing hands and eyes. The preparation of
      antineoplastic agents should be performed under hoods positioned away from heat
      sources and any air currents. It is advisable to use disposable surgical gowns
      with long sleeves with elastic cuffs or knitted sleeve to allow the gloves
      sticking above the gown itself. In the preparation of drugs the vial opening
      procedure must be implemented after verifying that no liquid is left at the top,
      and by wrapping the neck of the vial with a sterile gauze. Any accidental
      contamination must be reported to the Physician. All waste materials produced
      from the handling of cytotoxic chemotherapy should be considered as special
      hospital waste. To achieve high standards of safety and prevention for the
      personnel exposed to antineoplastic agents, it is necessary that workers are
      adequately informed about the risks and proper handling and disposal of
      anticancer drugs and contaminated materials.

PMID- 23559131
TI  - [When the conservative treatment in high-risk non-muscle invasive bladder cancer
      patients should be abandoned].
AB  - Despite the good quality of treatment expected with optimized transurethral
      resection (TUR) and adjuvant Bacillus Calmette-Guerin (BCG) regimen, many high
      risk non-muscle invasive bladder cancer (NMIBC) patients recur and progress.
      According to the EORTC Tables of risk, cases with a score of 10-17 and those with
      a score of 7-23 should be considered as being at high risk of recurrence and
      progression, respectively. AUA and NCCN consider all T1 stage tumors, high grade
      Ta and CIS at high risk of recurrence and progression. Long-term follow-up shows
      that T1,G3 patients treated with BCG will suffer from up to 45% and 17% rate of
      recurrence and progression, respectively. Consequently, EAU, AUA and NCCN
      Guidelines for bladder cancer recommend radical cystectomy as a first treatment
      option for those patients who failed after two cycles of adjuvant BCG. However,
      to date, there is no definitive evidence that in this special subgroup of
      patients an early radical cystectomy is better than any additional salvage
      strategy, in terms of oncologic outcome. On the other hand, it is well accepted
      that radical cystectomy is burdened with consistent reduction of overall post
      operative quality of life. The reluctance of patient to accept (and of surgeon to
      recommend) this major extirpative surgery may explain the reduced disease-free
      survival rate, well documented when radical cystectomy has been extremely
      delayed. Defining the criteria for the selection of BCG-failure patients for whom
      any conservative procedure should be definitively abandoned in favor of a timely
      radical cystectomy has become of critical importance. Recently, clinical,
      laboratory and pathologic acquisitions allowed the development of more accurate
      predictive factors for tumor progression in NMIBC. Among these factors, clinical
      type of BCG-failure, morphology and tumor growth patterns, pathologic sub-staging
      and immunohistochemistry will play a paramount role in decision-making with these
      patients in routine practice.

PMID- 23559132
TI  - [Adverse events after intravesical therapy: are we always ready to recognize and
      prevent them?].
AB  - Intravesical therapy is widely used in non-muscle-invasive bladder cancer (NMIBC)
      as adjuvant treatment after transurethral resection of bladder tumor (TURBT).
      Assuming that adjuvant therapy is necessary for NMIBC in order to reduce
      recurrence and progression rates, chemotherapy and BCG toxicity become a relevant
      issue. Both treatments may have local and systemic side effects, which can lead
      to treatment cessation, resulting in incomplete treatment and poor outcomes.
      Therefore, urologists, specialist nurses and patients must be aware of the
      possible adverse events in order to early recognize, prevent and treat them
      properly. This article summarizes the local and systemic side effects associated
      with intravesical therapy, presents the recommendations for an effective
      management of these adverse events based on currently available evidence, and
      highlights some open questions on these issues.

PMID- 23559133
TI  - [Endoscopic resection. Aspects of technique and optimization of outcomes. Current
      indications to PDD-guided resection].
AB  - Trans-Urethral Resection (TUR) of bladder tumors is the gold standard to make the
      correct diagnosis and remove all visible lesions. The strategy of resection
      depends on the size of the lesion. Small tumors can be resected en bloc, while
      larger tumors should be resected separately in fractions to obtain a correct
      pathological diagnosis. Random biopsies from normal-looking mucosa should be
      performed in patients with positive urinary cytology and absence of visible tumor
      in the bladder. As a standard procedure, cystoscopy and TUR are performed using
      white light. Photodynamic diagnosis (PDD) is most useful for detecting CIS, and
      therefore should be restricted to those patients with a suspected high-grade
      tumor.

PMID- 23559134
TI  - [Intravesical chemotherapy].
AB  - Bladder cancer care continues to represent a significant financial burden on the
      population and on the healthcare system. The incidence of bladder cancer has
      increased over the last two decades. Therapeutic advances have occurred in
      bladder cancer care, but at an increased cost to payers, providers, and patients.
      Intravesical treatment of non-muscle invasive tumors represents one of the main
      costs. For this reason therapeutic schedules need to be rationalized. In this
      perspective, we present some critical remarks on: the use of gemcitabine in
      clinical practice; the real impact of the perioperative chemotherapy, emphasizing
      the cost and effectiveness in high-risk patients, and finally the optimization of
      intravesical treatments. There is a need for the scientific community to focus on
      their resources and convey efforts not in the treatment of low-risk cancers
      (present in significant numbers in various studies), which the Anglo-Saxons call
      "nuisance tumor" since they can be treated easily and effectively at low cost,
      but definitely to engage in the study of the treatment of cancer at high risk of
      recurrence and progression, and it is on this field that the cost (economic,
      management, subjective) / benefit ratio must be assessed.

PMID- 23559135
TI  - [How to apply follow-up in relation to risk group].
AB  - The term 'Non-muscle invasive bladder cancer' identifies a heterogeneous disease
      due to different natural history of its various appearances. T1 stage represents
      a non-predictable population, which might respond to non-operative treatment
      strategies or to the need of a more aggressive treatment, in order to avoid the
      progression to invasive, and possibly to metastatic stages. In the first year
      following transurethral resection of bladder (TURB), tumor recurrence is seen in
      up to 45% of the population; of this, 15% may progress to muscle invasive or
      metastatic disease, or both. In order to control the recurrence and progression
      and identify invasive tumors at the earliest possible stage, it is strongly
      necessary to define individual patient risk assessment follow-up. To obtain exact
      staging, besides a proper transurethral resection of bladder, a restaging
      transurethral resection of bladder should be performed in T1 patients. Data from
      literature support the immediate postoperative intravesical instillation of
      different chemotherapeutic agents in low-risk patients. Multifocal papillary
      lesions might require a more intensive adjuvant regimen, whereas intravesical
      immunotherapy using Bacillus Calmette-Guerin is recommended in patients at high
      risk of progression. Early cystectomy should be considered in patients with
      recurrent T1 tumors or refractory carcinoma in situ to avoid unfavorable tumor
      progression.

PMID- 23559136
TI  - [Urine cytology and new markers. Are there any advantages in terms of cost
      effectiveness?].
AB  - Bladder cancer has the highest lifetime treatment and surveillance costs per
      patients for all cancers. New diagnostic tools, and ancillary tests, such as
      urine markers, have been developed to enhance the sensitivity for detecting
      cancer cells exfoliated from the urinary tract, and to reduce the discomfort of
      repeated cystoscopies. Several markers have been studied, and others are under
      investigation; a few provide some advantage, only in selected cases, in terms of
      detection rate and cost-effectiveness for the patient as well as the health
      service. This paper provides a concise update of the most promising urinary
      markers (nuclear matrix protein 22, ImmunoCyt, and fluorescence in situ
      hybridization) acting as non-invasive tests which help to identify urothelial
      cancers. Cystoscopy remains the most consistent examination for diagnosis and
      follow-up of non-muscle-invasive bladder cancer. However, some markers can be
      useful in understanding atypical cytology due to urinary tract phlogosis,
      infection, or treatment with chemotherapy or intravesical bacillus Calmette
      Guerin. Moreover, in centers with clinical experience, selected patients may
      benefit from the use of urinary markers to achieve prognostic information at the
      specific time of individual follow-up.

PMID- 23559137
TI  - [Endovesical treatment as an alternative to BCG for intermediate or high-risk NMI
      bladder cancer].
AB  - A shortage of BCG is foreseen till the end of 2013. Which will be the management
      of intermediate and high-risk NMI-BC if BCG will not be available? In patients
      harboring high-risk NMI tumors, particularly T1G3 and Tis, the first therapeutic
      choice is radical cystectomy. Device-assisted therapies, although showing
      promising results, should be considered only for selected patients. In
      intermediate risk patients, intravesical chemotherapy remains a legitimate option
      even if BCG is available. Thus, in a period of BCG shortage, intravesical
      chemotherapy should be offered, preferably preceded by early instillation,
      according to the EAU guidelines.

PMID- 23559138
TI  - [Second-line intravesical therapy. What is the present role of device-assisted
      therapy?].
AB  - Non-muscle-invasive bladder cancer is a common urinary malignancy whose
      management is a challenge: strong evidence supports the use of passive
      intravesical chemotherapy in the management of this tumor. Despite current
      guidelines, the treatment is suboptimal as illustrated by the high risk of
      recurrence and progression. Bacillus Calmette-Guerin (BCG) is the gold standard
      for the treatment of high-grade non-muscle-invasive bladder cancer, but in case
      of disease persistence, after 2 consecutive induction courses of BCG, patients
      must undergo radical cystectomy. We discuss options for second-line adjuvant
      therapy for non-muscle-invasive bladder cancer in standard treatment non
      responder patients. We investigated the use and application of device-assisted
      therapy for the intravesical treatment of bladder cancer, such as
      thermochemotherapy (TCT) and electromotive drug administration (EMDA). Many
      studies demonstrate their synergistic therapeutic effect, greater than the single
      treatment with chemotherapy, inducing an increased absorption of the
      chemotherapeutic agent (Mitomycin C) to the urothelium. TCT and EMDA are safe and
      effective in terms of outcomes. For the future it will be important to encourage
      the use of the existing technology within the appropriate clinical indications.

PMID- 23559139
TI  - Pulmonary function impairment and airway allergy among workers in traditional
      bakeries.
AB  - OBJECTIVES: To assess the effect of exposure to flour dust on pulmonary function
      tests, prevalence of symptoms (respiratory, allergic/irritating) and parameters
      of allergic sensitization in terms of skin prick test, and bronchial hyper
      responsiveness. MATERIAL AND METHODS: 43 bakers (with at least 2 years of
      occupational exposure) working at different bakeries in Ismailia city, Egypt; and
      64 control subjects of comparable socio demographic characteristics were
      compared. All participants were subjected to an interview questionnaire, clinical
      chest examination, skin prick test, bronchial hyper-responsiveness test and
      measurements of pulmonary function parameters. RESULTS: All respiratory and
      allergic symptoms were more prevalent among bakers compared to the control group,
      with the highest odds ratio for allergic symptoms (OR = 6.9; p < 0.0001) and
      dyspnea (OR = 6.3; p = 0.0004). Bakers had a higher percentage of SPT positive
      results with statistically significant difference between the two groups (p <
      0.0001). Bakers had lower observed values compared to the control group with
      statistically significant difference for FVC, FEV1/FVC ratio, FEF75%, and FEF25
      75% parameters. CONCLUSION: The present study suggested that occupational
      exposure to flour dust may affect respiratory irritation and sensitization, and
      reduce the pulmonary function tests such as FVC, FEV1, and FEV1/FVC ratio and
      FEF25-75%.

PMID- 23559140
TI  - A cytogenetic approach to the effects of low levels of ionizing radiation (IR) on
      the exposed Tunisian hospital workers.
AB  - OBJECTIVES: The aim of this study is to assess chromosomal damage in Tunisian
      hospital workers occupationally exposed to low levels of ionizing radiation (IR).
      MATERIALS AND METHODS: The cytokinesis-block micronucleus (CBMN) assay in the
      peripheral lymphocytes of 67 exposed workers compared to 43 controls matched for
      gender, age and smoking habits was used. The clastogenic/aneugenic effect of IR
      was evaluated using the CBMN assay in combination with fluorescence in situ
      hybridization with human pan-centromeric DNA in all the exposed subjects and
      controls. RESULTS: The study showed a significant increase of the micronucleus
      (MN) frequency in the lymphocytes of the exposed workers compared to the control
      group (13.63 +/- 4.90/00 vs. 6.52 +/- 4.210/00, p < 0.05). The centromere
      analysis performed in our study showed that MNs in hospital staff were
      predominantly centromere negative (72%) and the mean negative labeled
      micronucleus (C-MN) frequency was significantly higher in the exposed subjects
      than in the controls (9.04 +/- 4.570/00 vs. 1.17 +/- 0.770/00). The multivariate
      regression analysis, taking into account all confounding factors, showed that
      only the time of exposure to IR had a significant effect on the level of MNs and
      C-MN. CONCLUSION: The present study shows that chromosomal damage leading to the
      formation of micronucleated lymphocytes is more frequent in the hospital workers
      exposed to IR than in the controls, despite the low levels of exposure. The
      results of the study confirm the well-known clastogenic properties of ionizing
      radiation. In regards to health monitoring, detection of early genotoxic effects
      may allow for the adoption of preventive biological control measures, such as
      hygienic improvements in the workplace or reduction of hours of occupational
      exposure.

PMID- 23559141
TI  - Efficacy of psychological interventions for sexual dysfunction: a systematic
      review and meta-analysis.
AB  - Sexual dysfunction is highly prevalent in the general population and associated
      with psychological distress and impaired sexual satisfaction. Psychological
      interventions are promising treatment options, as sexual dysfunction is
      frequently caused by and deteriorates because of psychological factors. However,
      research into the efficacy of psychological interventions is rather scarce and an
      up-to-date review of outcome studies is currently lacking. Therefore, we
      conducted a systematic review and meta-analysis of all available studies from
      1980 to 2009 to examine the efficacy of psychological interventions for patients
      with sexual dysfunction. A total of 20 randomized controlled studies comparing a
      psychological intervention with a wait-list were included in the meta-analysis.
      The overall post-treatment effect size for symptom severity was d = 0.58 (95% CI:
      0.40 to 0.77) and for sexual satisfaction d = 0.47 (95% CI: 0.27 to 0.70).
      Psychological interventions were shown to especially improve symptom severity for
      women with Hypoactive Sexual Desire Disorder and orgasmic disorder. Our
      systematic review of 14 studies comparing at least two active interventions head
      to-head revealed that very few comparative studies are available with large
      variability in effect sizes across studies (d between -0.69 and 2.29 for symptom
      severity and -0.56 and 14.02 for sexual satisfaction). In conclusion,
      psychological interventions are effective treatment options for sexual
      dysfunction. However, evidence varies considerably across single disorders. Good
      evidence exists to date for female hypoactive sexual desire disorder and female
      orgasmic disorder. Further research is needed on psychological interventions for
      other sexual dysfunctions, their long-term and comparative effects.

PMID- 23559142
TI  - Reference levels and patient doses in interventional cardiology procedures in
      Greece.
AB  - OBJECTIVES: To present a national survey that was performed for the establishment
      of national reference levels (RLs) for interventional cardiology (IC) procedures
      and to estimate the effective dose (E) received by the patient during these
      procedures. METHODS: Data concerning the fluoroscopy time and air kerma-area
      product (P KA) during coronary angiography (CA), percutaneous coronary
      intervention (PCI), pacemaker implantation (PMI) and radiofrequency cardiac
      ablation (RFCA) from 26 centres were collected. Moreover, measurements concerning
      the performance of X-ray systems used in IC were performed in order to set system
      related reference levels. P KA to E conversion factors were also calculated.
      RESULTS: The suggested P KA RLs for CA, PCI, PMI and RFCA are 53 Gycm(2), 129
      Gycm(2), 36 Gycm(2) and 146 Gycm(2), respectively, and the estimated E to the
      patient from these procedures is 9.7 mSv, 26.8 mSv, 5.5 mSv and 20.4 mSv,
      respectively. Reference levels for the fluoroscopic dose rate and dose per frame
      during image acquisition at the entrance of a water phantom are 29 mGy/min and
      0.23 mGy/frame, respectively. CONCLUSIONS: The suggested RLs are comparable to
      those suggested by other studies. Additional information concerning the
      complexity of the procedures and patient pathology should be collected for future
      reevaluation of the suggested RLs. KEY POINTS: * The radiation dose imparted
      during fluoroscopically guided interventional procedures can be high *
      Understanding of reference levels might help optimise interventional
      cardiological procedures * Optimisation by changing the systems' settings seems
      feasible in some cases * Procedure complexity and the patient's clinical problem
      should be taken into account.

PMID- 23559143
TI  - Postpartum haemorrhage from ruptured pseudoaneurysm: efficacy of transcatheter
      arterial embolisation using N-butyl-2-cyanoacrylate.
AB  - OBJECTIVES: To evaluate the efficacy of transcatheter arterial embolisation (TAE)
      using N-butyl-2-cyanoacrylate (NBCA) in the treatment of postpartum haemorrhage
      (PPH) due to ruptured pseudoaneurysm. METHODS: From March 2004 to December 2010,
      33 patients underwent TAE using NBCA for massive PPH. Twenty-one patients (63.6
      %) were in coagulopathic condition. Angiograms and medical records were
      retrospectively reviewed to determine technical/clinical success, complications
      and recurrent haemorrhage after TAE. Telephone interviews were conducted to
      obtain fertility-related data. RESULTS: Emergent angiograms revealed ruptured
      pseudoaneurysms at the uterine (n = 17), vaginal (n = 14), internal pudendal (n =
      3) and obturator (n = 1) arteries, which were successfully embolised with NBCA.
      Four patients required additional embolisation of the uterine (n = 3) or ovarian
      artery (n = 1) with an absorbable gelatine sponge. Adequate haemostasis was
      achieved in 31 patients (93.9 %) after TAE. Two patients experienced persistent
      (n = 1) or recurrent (n = 1) haemorrhage, which required hysterectomy. There were
      no major embolisation-related complications. All 29 patients who were interviewed
      reported regaining of their regular menstruation. Nine patients had normal
      pregnancies and delivered healthy babies at full term. CONCLUSIONS: TAE using
      NBCA is an effective treatment of PPH from ruptured pseudoaneurysms. In
      particular, NBCA is a potent embolic material in patients with coagulopathy. It
      does not seem to adversely affect future fertility. KEY POINTS: * Transcatheter
      arterial embolisation is a safe and effective treatment for postpartum
      haemorrhage. * NBCA is potent embolic material to treat bleeding patients with
      severe coagulopathy. * NBCA does not seem to adversely affect future fertility.

PMID- 23559144
TI  - Caveolin and TGF-beta entanglements.
AB  - Transforming growth factor (TGF)-beta is a multifunctional cytokine acting during
      development, tissue homeostasis, regeneration processes, and disease progression.
      Due to its pleiotropic effects, tight regulation of the induced signaling
      cascades is mandatory. Caveolin proteins regulate a specific endocytic pathway
      and modulate diverse signaling pathways and thus have been related to severe
      disorders, for example, cancer and fibrosis. Caveolin affects TGF-beta/-Smad and
      non-Smad signaling in many ways and thus can determine the cellular outcome upon
      TGF-beta challenge. Reciprocal regulation of caveolin and TGF-beta is also
      evident, ranging from gene expression to miRNA regulation. Finally, there is in
      vivo evidence that this crosstalk influences disease development and progression.
      This review gives an overview about the multifaceted relations of caveolin and
      TGF-beta.

PMID- 23559145
TI  - Exploring the zebrafish embryo as an alternative model for the evaluation of
      liver toxicity by histopathology and expression profiling.
AB  - The whole zebrafish embryo model (ZFE) has proven its applicability in
      developmental toxicity testing. Since functional hepatocytes are already present
      from 36 h post fertilization onwards, whole ZFE have been proposed as an
      attractive alternative to mammalian in vivo models in hepatotoxicity testing. The
      goal of the present study is to further underpin the applicability of whole ZFE
      for hepatotoxicity testing by combining histopathology and next-generation
      sequencing-based gene expression profiling. To this aim, whole ZFE and adult
      zebrafish were exposed to a set of hepatotoxic reference compounds.
      Histopathology revealed compound and life-stage-specific effects indicative of
      toxic injury in livers of whole ZFE and adult zebrafish. Next-generation
      sequencing (NGS) was used to compare transcript profiles in pooled individual RNA
      samples of whole ZFE and livers of adult zebrafish. This revealed that
      hepatotoxicity-associated expression can be detected beyond the overall
      transcription noise in the whole embryo. In situ hybridization verified liver
      specificity of selected highly expressed markers in whole ZFE. Finally,
      cyclosporine A (CsA) was used as an illustrative case to support applicability of
      ZFE in hepatotoxicity testing by comparing CsA-induced gene expression between
      ZFE, in vivo mouse liver and HepaRG cells on the levels of single genes, pathways
      and transcription factors. While there was no clear overlap on single gene level
      between the whole ZFE and in vivo mouse liver, strong similarities were observed
      between whole ZFE and in vivo mouse liver in regulated pathways related to
      hepatotoxicity, as well as in relevant overrepresented transcription factors. In
      conclusion, both the use of NGS of pooled RNA extracts analysis combined with
      histopathology and traditional microarray in single case showed the potential to
      detect liver-related genes and processes within the transcriptome of a whole
      zebrafish embryo. This supports the applicability of the whole ZFE model for
      compound-induced hepatotoxicity screening.

PMID- 23559147
TI  - Clinical application of controlled aliasing in parallel imaging results in a
      higher acceleration (CAIPIRINHA)-volumetric interpolated breathhold (VIBE)
      sequence for gadoxetic acid-enhanced liver MR imaging.
AB  - PURPOSE: To determine whether a controlled aliasing in parallel imaging results
      in higher acceleration (CAIPIRINHA) technique can improve the image quality of
      three-dimensional (3D), T1-weighted gradient echo (T1w-GRE) imaging compared with
      the use of a standard, parallel acquisition technique (PAT). MATERIALS AND
      METHODS: Sixty-four patients who underwent liver MR on a 3 Tesla (T) scanner,
      were included in this study. Twenty minutes after the injection of 0.025 mmole/kg
      of gadoxetic acid, 3D T1w-GRE imaging (volumetric interpolated breathhold
      examination [VIBE]) was acquired twice using a generalized autocalibrating
      partially parallel acquisition (384 * 250 matrix, acceleration factor [AF] of 2)
      and a CAIPIRINHA (384 * 380 matrix, AF of 4), respectively. Qualitative image
      analysis was performed for two image sets. RESULTS: CAIPIRINHA-VIBE showed better
      hepatic vessel clarity and lesion conspicuity than standard VIBE (P < 0.05).
      CAIPIRINHA-VIBE in the coronal plane also provided better results of motion
      artifact and liver edge sharpness than the standard VIBE (P < 0.05). Despite the
      more apparent PAT artifact on CAIPIRINHA-VIBE than on standard VIBE (P < 0.05),
      CAIPIRINHA-VIBE showed better overall image quality. CONCLUSION: The CAIPIRINHA
      VIBE was able to provide a higher spatial resolution, T1-weighted imaging with
      better image quality compared with a standard VIBE.

PMID- 23559148
TI  - Unusual DaTscan results.

PMID- 23559149
TI  - FOLFOX4 plus cetuximab administered weekly or every second week in the first-line
      treatment of patients with KRAS wild-type metastatic colorectal cancer: a
      randomized phase II CECOG study.
AB  - BACKGROUND: This randomized phase II study investigated first-line chemotherapy
      plus cetuximab administered every second week in KRAS wild-type metastatic
      colorectal cancer. PATIENTS AND METHODS: Patients received FOLFOX4 plus either
      standard weekly cetuximab (arm 1) or cetuximab (500 mg/m(2)) every second week
      (arm 2), until disease progression or unacceptable toxicity. Primary end point
      was the objective response rate (ORR). Progression-free survival (PFS), overall
      survival (OS), disease control rate (DCR) and safety were also investigated. The
      study was not powered to establish non-inferiority, but aimed at the estimation
      of treatment differences. RESULTS: Of 152 randomized eligible patients, 75 were
      treated in arm 1 and 77 in arm 2; ORRs [53% versus 62%, odds ratio 1.40, 95%
      confidence interval (CI) 0.74-2.66], PFS [median 9.5 versus 9.2 months, hazard
      ratio (HR) 0.92, 95% CI 0.63-1.34], OS (median 25.8 versus 23.0 months, HR 0.86,
      95% CI 0.56-1.30) and DCR (87%) were comparable. HRs adjusted for baseline
      factors were 1.01 and 0.99 for PFS and OS, respectively. Frequencies of grade 3/4
      adverse events in arms 1 versus 2 were similar: most common were neutropenia (28%
      versus 34%) and rash (15% versus 17%). CONCLUSIONS: Activity and safety of
      FOLFOX4 plus either cetuximab administered weekly or every second week were
      similar.

PMID- 23559150
TI  - Identifying the target NSCLC patient for maintenance therapy: an analysis from a
      placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN).
AB  - BACKGROUND: This was a post hoc analysis of patients with non-squamous histology
      from a phase III maintenance pemetrexed study in advanced non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: The six symptom items' [average symptom
      burden index (ASBI)] mean at baseline was calculated using the lung cancer
      symptom scale (LCSS). Low and high symptom burden (LSB, ASBI < 25; HSB, ASBI >=
      25) and performance status (PS: 0, 1) subgroups were analyzed for treatment
      effect on progression-free survival (PFS) and overall survival (OS) using the Cox
      proportional hazard models adjusted for demographic/clinical factors. RESULTS:
      Significantly longer PFS and OS for pemetrexed versus placebo occurred in LSB
      patients [PFS: median 5.1 versus 2.4 months, hazard ratio (HR) 0.49, P < 0.0001;
      OS: median 17.5 versus 11.0 months, HR 0.63, P = 0.0012] and PS 0 patients (PFS:
      median 5.5 versus 1.7 months, HR 0.36, P < 0.0001; OS: median 17.7 versus 10.3
      months, HR 0.54, P = 0.0019). Significantly longer PFS, but not OS, occurred in
      HSB patients (median 3.7 versus 2.8 months, HR 0.50, P = 0.0033) and PS 1
      patients (median 4.4 versus 2.8 months, HR 0.60, P = 0.0002). CONCLUSIONS: ASBI
      and PS are associated with survival for non-squamous NSCLC patients, suggesting
      that maintenance pemetrexed is useful for LSB or PS 0 patients following
      induction.

PMID- 23559151
TI  - A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive
      breast cancer.
AB  - BACKGROUND: A multicenter NCI-sponsored phase II study was conducted to analyze
      the safety and efficacy of the combination of ixabepilone with trastuzumab in
      patients with metastatic HER2-positive breast cancer. PATIENTS AND METHODS: Two
      cohorts were enrolled: cohort 1 had received no prior chemotherapy or trastuzumab
      for metastatic disease and cohort 2 had received 1-2 prior trastuzumab-containing
      regimens for metastatic disease. Patients in both cohorts received ixabepilone 40
      mg/m(2) as a 3-h infusion and trastuzumab on day 1 of a 21-day cycle. Tumor
      biomarkers that may predict response to trastuzumab were explored. RESULTS:
      Thirty-nine women entered the study with 15 patients in cohort 1 and 24 patients
      in cohort 2. Across both cohorts, the overall RR was 44%, with a clinical benefit
      rate (CR + PR + SD for at least 24 weeks) of 56%. Treatment-related toxic effects
      included neuropathy (grade >=2, 56%), leukopenia (grade >=2, 26%), myalgias
      (grade >=2, 21%), neutropenia (grade >=2, 23%), and anemia (grade >=2, 18%).
      CONCLUSIONS: This represents the first study of the combination of ixabepilone
      with trastuzumab for the treatment of metastatic HER2-positive breast cancer.
      These results suggest that the combination has encouraging activity as first and
      subsequent line therapy for metastatic breast cancer.

PMID- 23559152
TI  - Primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs) in patients with non-small-cell lung cancer harboring TKI
      sensitive EGFR mutations: an exploratory study.
AB  - BACKGROUND: The mechanism of primary resistance to epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell
      lung cancer (NSCLC) has not been clearly understood. PATIENTS AND METHODS: Eleven
      patients exhibiting primary resistance (disease progression <3 months) were
      identified among 197 consecutive NSCLC patients with TKI-sensitive EGFR mutations
      who received EGFR TKIs at Seoul National University Hospital. Treatment-naive
      tumors were examined for concurrent genetic alterations using fluorescence in
      situ hybridization and targeted deep sequencing of cancer-related genes. Deletion
      polymorphism of Bcl-2-interacting mediator of cell death (BIM) gene was examined
      to validate its predictive role for TKI outcome. RESULTS: The median progression
      free survival (PFS) for patients receiving EGFR TKIs was 11.9 months, and the
      response rate 78.8%. Among the 11 patients exhibiting primary resistance, a de
      novo T790M mutation was identified in one patient, and two exhibited mesenchymal
      epithelial transition amplification and anaplastic lymphoma kinase fusion.
      Targeted deep sequencing identified no recurrent, coexistent drivers of NSCLC.
      Survival analysis revealed that patients with recurrent disease after surgery had
      a longer PFS than those with initial stage IV disease. However, BIM deletion
      polymorphism, line of treatment, EGFR genotype, and smoking were not predictive
      of PFS for EGFR TKIs. CONCLUSIONS: We identified coexistent genetic alterations
      of cancer-related genes that could explain primary resistance in a small
      proportion of patients. Our result suggests that the mechanism of primary
      resistance might be heterogeneous.

PMID- 23559153
TI  - Phase II study on lapatinib in advanced EGFR-positive chordoma.
AB  - BACKGROUND: To report on a prospective, investigator-driven, phase II study on
      lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma
      patients. PATIENTS AND METHODS: From December 2009 to January 2012, 18 advanced
      progressing chordoma patients entered this study (median age: 61 years; disease
      extent: metastatic 72% and locally advanced 28%). Epidermal growth factor
      receptor (EGFR) expression and activation were evaluated by immunohistochemistry
      and/or phospho-arrays, real-time polimerase chain reaction, fluorescence
      immunostaining. Fluorescence in situ hybridization analysis was also carried out.
      Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day),
      until progression or toxicity. The primary study end point was response rate (RR)
      as per Choi criteria. Secondary end points were RR by Response Evaluation
      Criteria in Solid Tumor (RECIST), overall survival, progression-free survival
      (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response
      (PR) + stable disease (SD) >= 6 months). RESULTS: All patients were evaluable for
      response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi
      responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6
      [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12)
      months, with a 22% CBR. CONCLUSIONS: This phase II study showed a modest
      antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR
      targeting in chordoma needs to be further investigated, both clinically and
      preclinically. Clinical trial Registration No: EU Clinical Trials Register trial
      no. 2009-014456-29.

PMID- 23559154
TI  - Detection of base excision repair enzyme activity using a luminescent G
      quadruplex selective switch-on probe.
AB  - We report herein a simple and convenient luminescent assay for detection of base
      excision repair enzyme activity using an Ir(III) complex as a G-quadruplex
      selective probe. Using uracil-DNA glycosylase (UDG) as a model enzyme, the assay
      achieved high sensitivity and selectivity for UDG over other tested enzymes. The
      utility of the assay for screening potential UDG inhibitors was also
      demonstrated.

PMID- 23559155
TI  - Amide-controlled highly selective catalytic borylcupration of allenes.
AB  - A novel copper-catalyzed, highly regio- and stereoselective borylcupration of
      substituted 2,3-allenamides with bis(pinacolato)diboron producing Z-beta
      borylated beta,gamma-unsaturated enoamides has been demonstrated. Due to the
      unique effect of the amide-group, perfect regio- and stereoselectivity and good
      to excellent yields have been achieved, which were rationalized by a DFT study.

PMID- 23559158
TI  - Characterization of the thrombospondin (TSP)-II gene in Penaeus monodon and a
      novel role of TSP-like proteins in an induction of shrimp sperm acrosome
      reaction.
AB  - We have recently shown that water-soluble materials from the egg extracellular
      cortical rods (wsCRs) exert the ability to induce the sperm acrosome reaction in
      Penaeus monodon. In this study, we further demonstrated that the thrombospondin
      protein family (TSP) existed in wsCRs, and that their mRNA transcripts were
      detected in developing oocytes as early as stage I. Full sequence analysis
      revealed that our pmTSP sequence was considerably different from the recently
      reported pmTSP in the 5' nonconserved region and in many TSP signature domains,
      hence, the name pmTSP-II was given to our variant. The transcripts of pmTSP-II
      were detected only in early developing oocytes (stage-I and -II) while TSP-like
      proteins were detected in all developing oocytes, particularly at the outer rim
      of cortical rods situated in the extracellular crypts of the mature, stage-IV
      oocytes. In addition, wsCRs contained anti-TSP-reactive proteins, suggesting that
      TSP-like proteins are dissolved in and are part of the egg water during spawning.
      The functional importance of TSP-like proteins was evident by the interference of
      a wsCR-induced acrosome reaction response with anti-TSP in a concentration
      dependent manner. In summary, we found that pmTSP-II transcripts were present in
      the developing oocytes and pmTSP-II protein accumulated in cortical rods, which
      are partly secreted and thus solubilized to produce dissolved TSP-like proteins
      that participate in induction of the sperm acrosome reaction-a novel reproductive
      role for TSP protein family.

PMID- 23559159
TI  - Optically clear alginate hydrogels for spatially controlled cell entrapment and
      culture at microfluidic electrode surfaces.
AB  - We describe an innovation in the immobilization, culture, and imaging of cells in
      calcium alginate within microfluidic devices. This technique allows unprecedented
      optical access to the entirety of the calcium alginate hydrogel, enabling
      observation of growth and behavior in a chemical and mechanical environment
      favored by many kinds of cells.

PMID- 23559160
TI  - Lichen simplex chronicus of the conjunctiva.

PMID- 23559157
TI  - Relationship of relaxin hormone and thumb carpometacarpal joint arthritis.
AB  - BACKGROUND: The female predominance in thumb carpometacarpal (CMC) joint
      arthritis has led to speculation that reproductive hormones or hypermobility are
      responsible. Evidence shows that patients with pathologic laxity have a higher
      rate of thumb CMC arthritis. Relaxin hormone increases laxity in the pelvic
      ligaments through upregulation of matrix metalloproteases (MMPs). It is thus a
      hormone of interest in the development of thumb CMC arthritis.
      QUESTIONS/PURPOSES: Our goals were to identify demographic and hormonal factors
      associated with joint laxity in patients with CMC arthritis and to evaluate the
      relationship among serum relaxin, relaxin receptors, and MMPs in the anterior
      oblique ligament (AOL) of the thumb. We hypothesized that serum relaxin was
      correlated with joint laxity as well as with relaxin receptors and MMPs in the
      AOL. METHODS: Forty-nine patients undergoing thumb CMC arthroplasty underwent
      laxity examination, blood draw, and AOL sampling. Ligaments were analyzed for
      relaxin receptor and MMPs 1 and 3 using quantitative reverse-transcriptase
      polymerase chain reaction. RESULTS: Women demonstrated more joint laxity than men
      (p < 0.001). RNA analysis confirmed relaxin receptors in the AOL as well as MMPs
      1 and 3. There was a significant correlation between serum relaxin and MMP-1 (p =
      0.04). Detectable serum relaxin was negatively correlated with relaxin receptors
      in the AOL (p = 0.02). CONCLUSIONS: Further studies are needed to evaluate the
      role of laxity and sex hormones in thumb CMC arthritis. CLINICAL RELEVANCE:
      Relaxin hormone may play a role in the development of arthritis at the thumb CMC
      joint. LEVEL OF EVIDENCE: Level I, prognostic study. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 23559161
TI  - Hypertrophic cardiomyopathy: a clinical and genetic update.
AB  - This article presents an overview of hypertrophic cardiomyopathy (HCM) and the
      associated clinical findings, treatment, and management for nurse practitioners.
      Topics include an overview of the condition, major and minor criteria for
      diagnosis, clinical course and pathophysiology, genetic inheritance and testing,
      and dysrhythmias associated with HCM.

PMID- 23559162
TI  - Skin of color: a basic outline of unique differences.
AB  - Darker skin differs from white skin in presentation, a tendency toward pronounced
      scarring, and pathophysiology of skin diseases common to those with skin of
      color. Recent studies highlight differences beyond the surface, which include
      issues of treatment, scar formation, collagen production, basic structure, and
      skin cancer development.

PMID- 23559163
TI  - A missense mutation in the sodium channel beta2 subunit reveals SCN2B as a new
      candidate gene for Brugada syndrome.
AB  - Brugada Syndrome (BrS) is a familial disease associated with sudden cardiac
      death. A 20%-25% of BrS patients carry genetic defects that cause loss-of
      function of the voltage-gated cardiac sodium channel. Thus, 70%-75% of patients
      remain without a genetic diagnosis. In this work, we identified a novel missense
      mutation (p.Asp211Gly) in the sodium beta2 subunit encoded by SCN2B, in a woman
      diagnosed with BrS. We studied the sodium current (INa ) from cells coexpressing
      Nav 1.5 and wild-type (beta2WT) or mutant (beta2D211G) beta2 subunits. Our
      electrophysiological analysis showed a 39.4% reduction in INa density when Nav
      1.5 was coexpressed with the beta2D211G. Single channel analysis showed that the
      mutation did not affect the Nav 1.5 unitary channel conductance. Instead, protein
      membrane detection experiments suggested that beta2D211G decreases Nav 1.5 cell
      surface expression. The effect of the mutant beta2 subunit on the INa strongly
      suggests that SCN2B is a new candidate gene associated with BrS.

PMID- 23559164
TI  - Nursing and care for the Brazilian Congress of Nursing: instrument of
      professional empowerment.

PMID- 23559165
TI  - [Nursing partnership with users in the defense of SUS].
AB  - This reflexive study aimed at presenting, based on the human rights framework,
      relevant elements for nursing care in the defense of the users of the Brazilian
      Single Health System (SUS). The assurance of health as a fundamental right and a
      government's responsibility was an achievement of the population through SUS,
      founded on the principles of universal, integral and equitable care, expanding
      the conception of health beyond the idea of the lack of disease, understood as
      quality of life. Nurses have a potential to perform a single role in the defense
      of the right to health and right to life and, by means of different partnerships,
      to strengthen the exercise of citizenship.

PMID- 23559166
TI  - [Professional competences of nurses and its management in a private hospital].
AB  - The objective of this research was to analyze how the professional competences of
      nurses of a private hospital (Belo Horizonte-MG) are configured and managed in
      their own perception. A descriptive case study was performed with a qualitative
      approach. The data from 15 interviews, including the application of a projective
      technique, were subjected to content analysis. The combination of practical and
      theoretical knowledge and the care for the patient were the core competences
      listed by the subjects, which are outsourced in various ways and managed
      primarily by themselves. Face the data and the limitations of the study,
      suggestions have been outlined for future research and for the actors involved.

PMID- 23559167
TI  - [Dengue Almanac: readings and narratives of Community Health Agents].
AB  - This article discusses the results of a reading-and-appropriation study, as an
      approach methodology to narrative universe of Health Community Agents (ACS),
      using the Dengue Almanac (AD), an information-communication device. Workshops
      with groups of ACS from Rio de Janeiro city were developed using the Almanac,
      aiming it's de-construction and relational reading, to improve the comprehension
      about knowledge's construction and appropriation on dengue and health, and
      evaluate the AD as an info-communicational device. The results were categorized
      within three axes: informational abundance during dengue's epidemics and silence
      between them, meaning non-information; the victim's blaming in health
      information's processes; ACS labor's contradictions and ambiguities as mediators.
      The Almanac proved to be a useful tool to discussion and appropriation of health
      information, due to the relational and non-linear reading characteristics of it's
      contents, and the interactive and nonauthoritative format of it's formulations on
      dengue and health.

PMID- 23559168
TI  - [Understanding the meaning of being hospitalized in daily lives of children and
      teenager with chronic diseases].
AB  - The study tried to understand the meaning of hospitalization for children and
      teenagers with chronic diseases substantiated on Symbolic Interactionism and
      developed from the qualitative Assistential Converging Research whose
      participants were a child and three teenagers. Data collection took place through
      a nursing interaction process, participating observation, sensible listening and
      child drawing. During the analysis, the meaning of hospitalization was expressed
      as being ill, away from home, feeling pain, sadness, suffering, wishing to cry,
      nervousness, aggressiveness and losing freedom. It was also understood as
      treatment, cure, support, friends, reciprocity with nature and "pleasant
      experiences" through care, passion, love, happiness and games. The participants'
      ability to show their view of the situation in which they are inserted was
      highlighted in their drawings, imbued with meanings and life lessons.

PMID- 23559169
TI  - [Youth and health: discourse analysis on supply and access to public facilities].
AB  - From the standpoint of sociodemographic, teens today represent an important
      portion of the Brazilian population. In 2005 the Brazilian government published
      the National Youth Policy. Despite of this, many teens still find difficulties in
      accessing public services, especially the ones involving health. This study aimed
      to analyze young students' speeches about the conditions of access to public
      services and health through qualitative research. The students inquired live in
      rural and urban areas of the city of Vitoria da Conquista - Bahia. The method
      used was the content analysis proposed by Bardin (1979) and Minayo (2006), and
      the technique of discussion groups for youth proposed by Weller (2006).

PMID- 23559170
TI  - [Men's Health Policy: perspectives of nurses for its implementation].
AB  - This is a qualitative research, aiming to describe and analyze the perception of
      nurses from the Family Health strategy on the importance and perspectives of
      implementation of the Men's Health Policy. It was developed in July 2011, in the
      Health Centers of Teresina-PI, with sixteen nurses. The data were obtained
      through semi-structured interviews; the speeches were categorized according to
      Bardin and analyzed in the light of the Symbolic Interactionism. The nurses
      consider this policy important and their prospects of implementation are
      supportive to the initiative of coping with difficulties for the inclusion of
      this group and related to the work process. It brings contributions on the
      current health situation of men and the assistance and consolidation of nursing
      care.

PMID- 23559171
TI  - [Profile of multiple trauma occurrences in motorcycle drivers attended by the
      SAMU of Teresina-PI].
AB  - The study aimed to investigate the profile of polytrauma occurrences in
      motorcycle drivers Service at Mobile Emergency Care of the county of Teresina-PI.
      We conducted a quantitative and documentary study, with information gathered
      through the medical records of that service, in 2009. Data collection was
      conducted from February to March of 2010. The motorcycles were involved in 84% of
      accidents, and men of 21 to 30 years old were the most affected. The weekend and
      the urban area recorded more cases. The musculoskeletal trauma (59%) stood out.
      The alcoholic victims numbered 12%. Mortality was of 1%. We conclude that it is
      essential to adopt educational measures to ensure the proper behavior of
      individuals in transit.

PMID- 23559172
TI  - [Care to the elderly in Campinas-SP: qualitative study of managers and
      politicians].
AB  - The study aimed to identify, describe and analyze the practices carried out in
      the health of the elderly in the city of Campinas-SP, in the perspective of the
      health government representatives of the elderly, based on the National Policies.
      This is a qualitative study with thematic content analysis, from the perspective
      of individuals who assume strategic roles in the conduct of policy directed to
      the elderly in the county. Five central themes emerged from their comments: time
      and places; access conditions; population demands; human resources; health
      promotion and prevention of diseases and disorders; management. Health practices
      for the elderly health in Campinas-SP are in development, need to be evaluated,
      extended and systematized in both, the structural issues of human resources,
      finance and management, and in direct assistance to the elderly.

PMID- 23559173
TI  - [Degree of dependence of hospitalized elderly according to the patients'
      classification system].
AB  - The study aimed to evaluate the degree of dependency of elderly inpatients,
      according to the classification system of patients, and to identify factors
      related to patient dependency to nursing care. Cross-sectional study with a
      sample of 161 elderly patients evaluated at the beginning, middle and end of
      hospitalization, according to the patient classification scale. It was identified
      a prevalence in the intermediate rating (52.2%); statistically significant
      association between the ages of 80 to 100 years with the middle and semi
      intensive classes; 40% of the elderly classified to the semi-intensive care had
      death as the outcome. The aging process must determine specific nursing care for
      this population group, ensuring the quality of care.

PMID- 23559174
TI  - [Dependence to feed itself and food consumption in hospitalized elderly].
AB  - The objective of the study was to verify the association of food intake and the
      dependence to be fed in hospitalized elderly individuals who were interviewed in
      the first 24 hours after admission to a general hospital. Participated in the
      research 75 individuals average 70.9 years old, being 58.7% male and 17.3%
      showing dependence to be fed. There was no evident association between dependence
      to be fed and the intake of energetic and muscle building food, but there was an
      association with regulator food such as garlic and onion (p=0.00) and water
      (p=0.04). The need of nutritional orientation to the caretakers is suggested,
      taking into consideration that the feeding dependence is associated to a low
      intake of water among elderly individuals.

PMID- 23559175
TI  - [Workshops for cognitive stimulation adapted for elderly illiterate individuals
      with mild cognitive impairment].
AB  - The aim of this study was to assess the self-perception of memory in elderly
      illiterate with mild cognitive impairment, before and after workshops of
      cognitive stimulation adapted for illiterate individuals. The research was
      qualitative, held at the Health Unit of Taguatinga-DF, involving 63 elderly
      illiterate: 22 in the experimental group (EG), with 10 workshops; 21 in control
      group 1 (CG1), with 10 lectures; and 20 in the control group 2 (GC2), without
      intervention. Semi-structured interviews were carried on before and after the
      interventions, asking about memory status. The activities offered weekly to EG
      and CG1 have had two hours of duration. The mean age of the participants was 72.8
      years, and 92% were female. In pre-intervention, 82% reported worsening memory
      during the last year. In post-intervention, CG1 and CG2 kept memory changes,
      while EG improved cognition. One concludes that the provided workshops and
      lectures improved functionality and socialization / integration.

PMID- 23559176
TI  - [Costs and consumption of material resources in pediatric intensive and semi
      intensive care units].
AB  - Cost management of hospital material resources is a trendy research topic,
      especially in specialized health units. Nurses are pointed out as the main
      managers for costs and consumption of hospital materials resources. This study
      aimed to characterize Pediatric Intensive and Semi-Intensive Care Units of a
      teaching hospital and investigate costs and consumption of material resources
      used to treat patients admitted to these units. This is a descriptive exploratory
      study with retrospective data and quantitative approach. Data were obtained from
      a Hospital Information System and analyzed according to the ABC classification.
      The average expenditures were similar in both the neonatal and cardiac units, and
      lower in Pediatric Intensive and Semi-Intensive care units. There was a
      significant variation in the monthly consumption of materials. Higher cost
      materials had a greater impact on the budget of the studied units. The data
      revealed the importance of using a systematic method for the analysis of
      materials consumption and expenditure in pediatric units. They subsidize
      administrative and economic actions.

PMID- 23559177
TI  - [Situational low self-esteem in pregnant women: an analysis of accuracy].
AB  - To investigate the accuracy of defining characteristics of Situational low self
      esteem we developed a cross-sectional study, with 52 pregnant women assisted in a
      family centre. The NANDA-I taxonomy was used as well as the Rosenberg's scale.
      The diagnosis was present in 32.7% of the sample and all characteristics
      presented statistical significance, except "Reports verbally situational
      challenge to its own value". The characteristics "Indecisive behavior" and
      "Helplessness expressions" had 82.35% of sensitivity. On the other hand, the
      characteristics "Expression of feelings of worthlessness" and "Reports verbally
      situational challenge to its own value" were the more specific, with 94.29% of
      specificity. These results can contribute with the nursing practice because the
      identification of accurate characteristics is essential to a secure inference.

PMID- 23559178
TI  - [Characterization of physical violence experienced by prostitutes living inside
      the state of Piaui].
AB  - This is a descriptive exploratory study with a quantitative approach, which aimed
      to characterize the physical violence suffered by prostitutes of Piaui and
      identify the prevalence of this disease. The study included 76 prostitutes
      registered in the Association of Sex Professionals of Picos, county of the state
      of Piaui, Brazil. The data collection was conducted in the areas of prostitution
      and in the association, from September to October 2010. The results showed that
      most prostitutes were young, with low income, low education, had more than two
      years in prostitution (50%), being mainly affected by psychological violence
      (60.5%) followed by physical (30.2%). The aggressors were known to the victims
      and women hardly made the complaint. The results were enlightening and led to
      affirm that it is common the occurrence of violence in women prostitutes, because
      they work in places determinants of violent acts.

PMID- 23559179
TI  - [Production of knowledge on health promotion and nurse's practice in primary
      health care].
AB  - This is an integrative review that examines the national scientific production on
      health promotion and nurse's practice in the field of primary health care. With
      the development of the study, it was found that the discussion of this theme is
      little explored in nursing and that health promotion is still understood as
      synonymous of health education and / or prevention of disease. It is concluded
      that health education is an essential strategy to achieve the health promotion,
      understanding that one is not restricted to the other. Moreover, it is necessary
      that nurses recognize health promotion as a field of practice can transform
      social reality and their own practice.

PMID- 23559180
TI  - [Perinatal outcome in women suffering from chronic hypertension: literature
      integrative review].
AB  - The study aimed to identify patterns in the evolution of risk of perinatal
      outcomes of pregnant women with chronic hypertension in order to compare the
      results of the pregnancy outcome. It was held an integrative literature with time
      span between the years 1990 and 2010, in the databases LILACS, SciELO and
      MEDLINE. As results, it was observed that pregnant women had chronic hypertensive
      superimposed preeclampsia (20% to 78%), fetal growth restriction (8.5% to 30.7%),
      prematurity (32.4% to 86.4%), cesarean section (69 2%), placental abruption
      (3.75% to 8.4%), fetal death (9.5% to 27.2%), cardiovascular complications,
      maternal kidney and lung. We conclude that the association of chronic
      hypertension and pregnancy shows strong risk for maternal and perinatal
      complications, especially when associated with the severity and etiology of
      hypertension, showing no trend during the two decades studied on perinatal
      outcome.

PMID- 23559181
TI  - [Nursing interventions for the care of patients with arthritis: an integrative
      review].
AB  - This integrative review aimed to analyze the scientific literature related to
      nursing care for patients with arthritis. Twelve experimental studies were
      included, randomized and controlled, published in CINAHL, MEDLINE, SciELO and
      LILACS databases, using the controlled keywords "arthritis" and "nursing". The
      results indicated the effectiveness of music therapy, neuromuscular electrical
      stimulation, therapeutic touch and guided imagery associated with relaxation, for
      the treatment of pain. Being treated by a specialist nurse increased satisfaction
      with care, improved the impact of the disease and increased the demand for health
      services. Specific educational programs for people with arthritis stimulated the
      practice of physical exercises and those targeted to people with chronic
      conditions in general were effective to control pain and functional disability.
      We conclude that there is a set of interventions that can support the practice of
      evidence-based nursing for the elderly people with arthritis.

PMID- 23559182
TI  - [Convergent Care Research: use in developing models of nursing care].
AB  - The present text is a theoretical reflection upon the importance of Nursing care
      models for the consolidation of this discipline, concerning the contribution of
      Convergent Care Research (Pesquisa Convergente Assistencial -PCA) in elaborating
      such models. Beyond this, this article discusses the importance of Convergent
      Care Research in the convergence of the academic and practical worlds of nursing,
      which aid towards a safe practice, systematize care, and establish connections
      between pragmatism and scientism, leading nurses to adopt more solid knowledge
      construction postures.

PMID- 23559183
TI  - [School Health Program implementation in Fortaleza-CE: performance of the Family
      Health Strategy staff].
AB  - This work reports the experience of implementation of the School Health Program
      (PSE) by a team from the Family Health Strategy (FHS) in a public school in
      Fortaleza-CE, Brazil. The activities included conference about the deployment of
      the PSE with teachers and members of the FHS, workshops with students, clinical
      and dental assessment for adolescents and delivery of Booklets of Adolescent
      Health. The implementation of the PSE allowed health professionals to perceive
      their social role as educators and provided adolescents a greater contact with
      the staff from FHS. The rapprochement between the school and the FHS is crucial
      to help teenagers to transform scientific knowledge into healthy behaviors.

PMID- 23559185
TI  - [Letter from Porto Alegre].

PMID- 23559184
TI  - [Superficial venous formation of the cubital fossa: aspects of interest for
      nursing practice].
AB  - The aim of this study is to contribute to the knowledge to assists the nursing
      staff to identify the most common types of venous formations of the cubital fossa
      region, and also focus on the importance of always being alert to unusual cases
      as that reported here. Through a literature review, we found that the venous
      formations of this region can be classified into five common types, bring the
      Type II the was most frequent. We also found that MCV is considered the best
      puncture site, followed by MBV. We also describe an anatomical variation, in
      which we observed the absence of communication between BV and CV at the level of
      cubital fossa draining into BV and MVF, with the presence of the ACV.

PMID- 23559188
TI  - Sexual dimorphism in adipose tissue function as evidenced by circulating
      adipokine concentrations in the fasting state and after an oral glucose
      challenge.
AB  - STUDY QUESTION: Do the circulating levels of a panel of adipokines involved in
      glucose metabolism exhibit sexual dimorphism in the fasting state and after an
      oral glucose load? SUMMARY ANSWER: Our results indicate sexual dimorphism in the
      circulating concentrations of adipokines involved in intermediate metabolism in
      the fasting state and during an oral glucose load. This finding suggests an
      influence of sex steroids on adipose tissue function. WHAT IS KNOWN ALREADY:
      Sexual dimorphism in adipose tissue distribution fully develops after puberty and
      modulates the risk for cardiometabolic disorders. However, the possibility that
      adipose tissue function exhibits sexual dimorphism as well as its distribution is
      unproved. STUDY DESIGN, SIZE, DURATION: Cross-sectional case-control study
      including 32 subjects. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixteen subjects
      with weight excess (8 men and 8 women, including 4 overweight and 4 obese
      subjects in each group) and 16 normal weight healthy volunteers (8 men and 8
      women) presenting with similar age were submitted to a 75-g oral glucose
      tolerance test (oGTT). We measured circulating concentrations of insulin,
      glucose, chemerin, lipocalin-2, omentin-1, leptin and adiponectin and calculated
      their areas under the oGTT curve (AUC). MAIN RESULTS AND THE ROLE OF CHANCE:
      Leptin and adiponectin concentrations were higher throughout the oGTT in women
      compared with men. Lipocalin-2 concentrations decreased during the oGTT in the
      whole group of study subjects. However, these levels remained higher in men with
      weight excess compared with normal weight men, whereas in women with weight
      excess lipocalin-2 levels at the end of the oGTT were lower compared with normal
      weight women. Sex was among the main determinants of the AUC of omentin-1 and
      leptin in linear regression models, and lower estradiol and testosterone
      concentrations were related to higher AUC of chemerin and omentin-1,
      respectively. Subjects with weight excess had higher AUC of chemerin and leptin
      and lower AUC of omentin-1 and adiponectin levels, independently of sex.
      LIMITATIONS, REASONS FOR CAUTION: We included a relatively small sample size and,
      because this was a cross-sectional study, we cannot infer causality to the
      associations between the changes in circulating adipokine concentrations and the
      variables studied here. WIDER IMPLICATIONS OF THE FINDINGS: Sexual dimorphism in
      adipose tissue function should be considered when studying adiposity and obesity,
      and also when designing strategies for their diagnosis and management.

PMID- 23559187
TI  - Genome-wide microRNA expression profiling in idiopathic non-obstructive
      azoospermia: significant up-regulation of miR-141, miR-429 and miR-7-1-3p.
AB  - STUDY QUESTION: What is the profile of miRNAs in seminal plasma of patients with
      non-obstructive azoospermia (NOA)? SUMMARY ANSWER: miR-141, miR-429 and miR-7-1
      3p are significantly increased in seminal plasma of patients with NOA compared
      with fertile controls. WHAT IS KNOWN ALREADY: There is currently an urgent need
      to develop a noninvasive diagnostic test for NOA. Altered microRNA (miRNA)
      profiles have been proposed as potential biomarkers for the diagnosis of disease
      states. STUDY DESIGN, SIZE, DURATION: A total of 200 subjects (n = 100 for NOA, n
      = 100 for fertile control) were recruited to participate in this study.
      Recruitment took place from May 2008 to June 2010. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: We employed a strategy consisting of initial screening by
      TaqMan Low Density Array then further validation with a TaqMan quantitative RT
      PCR assay. Validation of the profiling results was conducted in two independent
      phases. In addition, the expression of the three validated seminal plasma miRNAs
      (sp-miRNAs) was examined in testicular tissues of patients with NOA and of
      fertile controls. Methylation status and functional analyses were also performed
      for the identified sp-miRNAs. MAIN RESULTS AND THE ROLE OF CHANCE: miR-141, miR
      429 and miR-7-1-3p were significantly increased in seminal plasma of patients
      with NOA compared with fertile controls. As sensitive and specific biomarkers,
      the profiling of these three identified sp-miRNAs provides a novel noninvasive,
      semen-based test for NOA diagnosis. The methylation status of these sp-miRNAs was
      inversely associated with their expression patterns. Additionally, we found that
      Cbl and Tgfbeta2 were down-regulated by miR-141, while Rb1 and Pik3r3 were down
      regulated by miR-7-1-3p. LIMITATIONS, REASONS FOR CAUTION: miRNA expression
      profile was investigated in seminal plasma samples from only a small number of
      NOA patients. In future investigations, a larger sample size should be adopted
      and the functional role of the three sp-miRNAs should be further characterized in
      animal models. WIDER IMPLICATIONS OF THE FINDINGS: Given that sp-miRNAs show
      reproducible and stable expression levels, they are potentially novel noninvasive
      biomarkers for the diagnosis of NOA. We propose that the three sp-miRNAs
      described above may participate in a methylation-miRNA-gene network related to
      NOA development. This work provides a foundation for interpretation of miRNA
      changes associated with pathogenesis of NOA and extends the current understanding
      of human NOA pathogenesis.

PMID- 23559189
TI  - Heparin and cAMP modulators interact during pre-in vitro maturation to affect
      mouse and human oocyte meiosis and developmental competence.
AB  - STUDY QUESTION: Does heparin ablate the advantageous effects of cyclic adenosine
      mono-phosphate (cAMP) modulators during pre-in vitro maturation (IVM) and have a
      deleterious effect in standard oocyte IVM? SUMMARY ANSWER: Heparin interrupts
      energy metabolism and meiotic progression and adversely affects subsequent
      development of oocytes under conditions of elevated cAMP levels in cumulus-oocyte
      complexes (COCs) after pre-IVM treatment with forskolin. WHAT IS KNOWN ALREADY:
      In animal IVM studies, artificial regulation of meiotic resumption by cAMP
      elevating agents improves subsequent oocyte developmental competence. Heparin has
      no effect on spontaneous, FSH- or epidermal growth factor (EGF)-stimulated
      meiotic maturation. STUDY DESIGN, SIZE, DURATION: An in vitro cross-sectional
      study was conducted using immature mouse and human COCs. Depending on individual
      experimental design, COCs were treated during pre-IVM with or without heparin, in
      the presence or absence of forskolin and/or 3-isobutyl-1-methylxanthine (IBMX),
      and then COC function was assessed by various means. PARTICIPANTS/MATERIALS,
      SETTINGS, METHODS: Forty-two women with polycystic ovaries (PCOs) or polycystic
      ovarian syndrome (PCOS) donated COCs after oocyte retrieval in a non-hCG
      triggered IVM cycle. COCs were collected in pre-IVM treatments and then cultured
      for 40 h and meiotic progression was assessed. COCs from 21- to 24-day-old female
      CBA F1 mice were collected 46 h after stimulation with equine chorionic
      gonadotrophin. Following treatments, COCs were checked for meiotic progression.
      Effects on mouse oocyte metabolism were measured by assessing oocyte
      mitochondrial membrane potential using JC-1 staining and oocyte ATP content. Post
      IVM mouse oocyte developmental competence was assessed by in vitro fertilization
      and embryo production. Blastocyst quality was evaluated by differential staining
      of inner cell mass (ICM) and trophectoderm (TE) layers. MAIN RESULTS AND THE ROLE
      OF CHANCE: In the absence of heparin in pre-IVM culture, the addition of cAMP
      modulators did not affect human oocyte MII competence after 40 h. In standard
      IVM, heparin supplementation in pre-IVM did not affect MII competence; however,
      when heparin was combined with cAMP modulators, MII competence was significantly
      reduced from 65 to 15% (P < 0.05). In mouse experiments, heparin alone in pre-IVM
      significantly delayed germinal vesicle breakdown (GVBD) so that fewer GVBDs were
      observed at 0 and 1 h of IVM (P < 0.05), but not by 2 or 3 h of IVM. Combined
      treatment with IBMX and forskolin in the pre-IVM medium produced a large delay in
      GVBD such that no COCs exhibited GVBD in the first 1 h of IVM, and the addition
      of heparin in pre-IVM further significantly delayed the progression of GVBD (P <
      0.05), in a dose-dependent manner (P < 0.01). Combined IBMX and forskolin
      treatment of mouse COCs during pre-IVM significantly increased mitochondrial
      membrane potential and ATP production in the oocyte at the end of pre-IVM (P <
      0.05), and significantly improved fertilization, embryo development and quality
      (P < 0.05). However, heparin abolished the IBMX + forskolin-stimulated increase
      in mitochondrial membrane potential and ATP production (P < 0.05), and adversely
      affected embryonic cleavage, development rates and embryo quality (P < 0.05).
      This latter adverse combinational effect was negated when mouse COCs were
      collected in heparin and IBMX for 15 min, washed and then cultured for 45 min in
      IBMX and forskolin without heparin. LIMITATION, REASONS FOR CAUTION: Experiments
      in mice found that heparin ablation of the advantageous effects of cAMP
      modulators during pre-IVM was associated with altered oocyte metabolism, but the
      mechanism by which heparin affects metabolism remains unclear. WIDER IMPLICATIONS
      OF THE FINDINGS: This study has revealed a novel and unexpected interaction
      between heparin and cAMP modulators in pre-IVM in immature mouse and human
      oocytes, and established a means to collect oocytes using heparin while
      modulating oocyte cAMP to improve developmental potential.

PMID- 23559190
TI  - Native acetabular version: 3D CT analysis ?of the psoas valley.
AB  - Insufficient version has been demonstrated to be a significant factor in
      increasing metal-on-metal cup wear. Another implication is the impingement of the
      psoas tendon at the anatomical depression on the anterior acetabular rim, called
      the psoas valley. It is not known whether the psoas valley has any anatomical
      significance when measuring native version. The effect of this landmark on the
      measurement of acetabular version has not been assessed using 3D CT.?Sixty five
      high resolution CT scans of non-diseased hips (performed for colonography) were
      used to measure the anatomical version angles of the bony acetabular rim. Our new
      method, using the psoas valley, was compared to the reference method, which used
      the full 320 degrees  of the acetabular rim. The measurement of acetabular
      version was highly reproducible between the methods. Both methods measured the
      angle of version over a wide range: 5 degrees  to 35 degrees  for males and 10
      degrees  to 40 degrees  for females. There were no statistically significant
      differences between genders (p = 0.3670). The Bland-Altman 1.96 SD lower and
      upper limits of agreement between the two methods were +4.6 degrees  and -4.3
      degrees , respectively. Intra-observer and inter-observer reliability were high
      for the new method. This adds to our understanding of native bony anatomy, and
      specifically provides a landmark that 3D CT has demonstrated to be potentially
      useful in assessing native version.

PMID- 23559191
TI  - Acetabular revision arthroplasty: using the Hastings bipolar head to enable
      retention of a well-fixed monoblock stem.
AB  - We describe a novel technique of combining the Hastings bipolar head, matched in
      size to the acetabular cup liner, with a fixed, cemented monoblock stem allowing
      for isolated uncemented acetabular revision arthroplasty. AIM: To assess patient
      clinical and radiological outcomes after isolated uncemented acetabular revision
      arthroplasty using the Hastings bipolar head. METHODS: Clinical outcome was
      assessed with the Oxford and WOMAC hip scores.?Radiographs were assessed
      preoperatively for acetabular defects. Post operative osseointegration of the
      acetabular cup was then classified and the femoral stem was examined for signs of
      loosening. RESULTS: Nine acetabular components were revised in eight patients.
      Preoperative acetabular defects ranged from Paprosky type 1 to 3A. There were no
      significant intra or postoperative complications. At a mean final follow-up of 15
      months, the Oxford hip score improved from an average of 17.5 preoperatively to
      44.1, and the WOMAC score had improved from 44.1 to 90.9. Eight acetabular cups
      demonstrated three or more signs of osseointegration with the remaining cup
      showing two signs. There were no signs of loosening of the retained femoral
      stems. CONCLUSION: These short term results of the use of the Hastings bipolar
      head in isolated uncemented acetabular revision arthroplasty demonstrate good
      patient outcomes, reduced morbidity, decreased technical difficulties for the
      surgeon and reduced expense for the health service.

PMID- 23559192
TI  - Acetabular configuration and its impact on cup coverage of a subtype of Crowe
      type 4 DDH with bi-pseudoacetabulum.
AB  - The purpose of this study was to explore the acetabular configuration of a
      special subtype of Crowe type 4 DDH and its impact on cup coverage, which was
      identified with a particular bi-pseudoacetabulum and an inter-pseudoacetabulum
      spine structure. The altered bone stock and anatomic structures were believed to
      be a result of lesser trochanter impingement on the pelvis as observed in all
      hips of this series, which was supported by the radiographic and intraoperative
      findings. Acetabular characteristics were depicted by means of radiographic
      assessment and direct observation during surgery. Preoperatively, the horizontal
      distance to the hip centre was 80.5 mm on average and 52.9 mm for femoral head
      height with a significant difference compared to the general series of DDH cases.
      Anterosuperior bony coverage was found ?to be more adequate with a thicker
      anterior wall. The postoperative hip centre was restored to the true acetabulum
      to within 23.4 mm vertically and 25.2 mm horizontally, and sufficient cup
      containment was achieved when the acetabular inclination angle was below 45
      degrees . A larger diameter cup (range 46-50 mm) was employed. No structural bone
      graft was required, and the medial protrusion technique was infrequently
      required. This subtype of DDH facilitated cup coverage during THA.

PMID- 23559193
TI  - Periprosthetic femoral fractures: treatments ?and outcomes. An analysis of 47
      cases.
AB  - We evaluated the treatment and outcome of 47 cases of periprosthetic femoral
      fracture presenting to our unit over a nine-year period. The average follow-up
      period was 48 months ?(range 24-114). Surgical treatment involved stem revision
      in 29 hips, open reduction and internal fixation in 11 hips and conservative
      treatment in seven hips. The mean HHS at the most recent ?follow-up was 74 (range
      49-91). Twenty-five patients were pain-free (53%), 10 patients had occasional
      mild pain (21%), eight patients had a limp and pain (17%) and four patients had
      severe disability (9%). Postoperative radiographs showed complete fracture union
      in all 47 patients. There were 11 complications: three further periprosthetic
      fractures, two aseptic loosenings, two dislocations, two aseptic loosenings of
      the primary prostheses, one stem breakeage, and one intraoperative fracture. Our
      results suggest cementless revision with tapered fluted stems used without
      cortical strut grafts are a valid procedure for the treatment of Vancouver B2 and
      B3 periprosthetic fractures. 

PMID- 23559194
TI  - The management of the displaced medial wall in complex acetabular fractures using
      plates and additional cerclage.
AB  - Reduction for displaced quadrilateral plates in complicated acetabular fractures
      is difficult and requires wide exposure. The purpose of this study is to assess
      the usefulness of the additional cable in this complicated fracture and to
      evaluate the potential danger of compressing the superior gluteal artery and
      nerve with cable application. We evaluated 31 hips (these included 25 hips with
      fractures of both columns, two posterior wall and column fractures, three
      anterior column and posterior hemitransverse fractures, and one high T-shaped
      fracture) with an average six-year follow-up. Clinical outcomes were evaluated
      using a modification of the Matta grading system and radiographic arthritic
      grades. We assessed the postoperative clinical outcomes in relation with other
      variables such as anatomical reduction, delayed operation, seagull sign, and
      femoral head injuries. We determined whether the superior gluteal artery and
      nerve were compressed by cerclage with the help of femoral angiography and EMG.
      Clinical outcomes were graded as very good to excellent for 18 patients, good for
      five, fair for three ?and poor for five. Preoperative femoral head injury (P =
      0.011), a seagull sign (P = 0.001), poor reduction (P = 0.015), and delayed
      reduction (P = 0.05) were found to statistically influence clinical results. We
      found that there were no injuries to the superior gluteal artery and nerve in
      spite of using a cable. Cerclage methods can be useful for initial reduction of
      displaced medial plates in acetabular fractures. These methods reduce operation
      time and blood loss as compared with other methods.

PMID- 23559195
TI  - Validity of the 3D VECTRA photogrammetric surface imaging system for cranio
      maxillofacial anthropometric measurements.
AB  - PURPOSE: The use of three-dimensional (3D) photography for anthropometric
      measurements is of increasing interest, especially in the cranio-maxillofacial
      field. Before standard implementation, accurate determination of the precision
      and accuracy of each system is mandatory. METHODS: A mannequin head was labelled
      with 52 landmarks, and 28 three-dimensional images were taken using a
      commercially available five-pod 3D photosystem (3D VECTRA; Canfield, Fairfield,
      NJ) in different head positions. Distances between the landmarks were measured
      manually using a conventional calliper and compared with the digitally calculated
      distances acquired from labelling by two independent observers. The experimental
      set-up accounted for clinical circumstances by varying the positioning (vertical,
      horizontal, sagittal) of the phantom. RESULTS: In the entire calliper measurement
      data set (n = 410), a significant difference (p = 0.02) between the directly
      measured and corresponding virtually calculated distances was found. The mean
      aberration between both modalities covering all data was 7.96 mm. No differences
      (p = 0.94) between the two groups were found using a cut-off of 10 % (leaving n =
      369 distances) due to considerable errors in direct measurements and the
      necessary manual data translation. The mean diversity of both measurement
      modalities after cut-off was 1.33 mm (maximum, 6.70 mm). Inter-observer analysis
      of all 1,326 distances showed no difference (p = 0.99; maximal difference, 0.58
      mm) in the digital measurements. CONCLUSION: The precision and accuracy of this
      five-pod 3D photosystem suggests its suitability for clinical applications,
      particularly anthropometric studies. Three-hundred-and-sixty degree surface
      contour mapping of the craniofacial region within milliseconds is particularly
      useful in paediatric patients. Proper patient positioning is essential for high
      quality imaging.

PMID- 23559196
TI  - West nile virus infection and myasthenia gravis.
AB  - INTRODUCTION: Viruses are commonly cited as triggers for autoimmune disease. It
      is unclear if West Nile virus (WNV) initiates autoimmunity. METHODS: We describe
      6 cases of myasthenia gravis (MG) that developed several months after WNV
      infection. All patients had serologically confirmed WNV neuroinvasive disease.
      None had evidence of MG before WNV. RESULTS: All patients had stable neurological
      deficits when they developed new symptoms of MG 3 to 7 months after WNV
      infection. However, residual deficits from WNV confounded or delayed MG
      diagnosis. All patients had elevated acetylcholine receptor (AChR) antibodies,
      and 1 had thymoma. Treatment varied, but 4 patients required acetylcholinesterase
      inhibitors, multiple immunosuppressive drugs, and intravenous immune globulin or
      plasmapheresis for recurrent MG crises. CONCLUSIONS: The pathogenic mechanism of
      MG following WNV remains uncertain. We hypothesize that WNV-triggered
      autoimmunity breaks immunological self-tolerance to initiate MG, possibly through
      molecular mimicry between virus antigens and AChR subunits or other autoimmune
      mechanisms.

PMID- 23559197
TI  - Spreading and fluorescence in situ hybridization of male and female meiocyte
      chromosomes from Arabidopsis thaliana for cytogenetical analysis.
AB  - Advances in molecular biology and in the genetics of Arabidopsis thaliana have
      led to it becoming an important model for the analysis of meiosis in plants.
      Cytogenetic investigations are pivotal to meiotic studies and a number of
      technological improvements for Arabidopsis cytology have provided a range of
      tools to investigate chromosome behavior during meiosis. This chapter contains a
      detailed description of cytological techniques currently used in our laboratory
      for the basic preparation of meiotic chromosomes for investigation of the female
      and male meiotic pathway and fluorescence in situ hybridization (FISH) analysis
      for the frequency and distribution of crossovers (chiasmata) at metaphase I.

PMID- 23559198
TI  - Analysis of plant meiotic chromosomes by chromosome painting.
AB  - Chromosome painting (CP) refers to visualization of large chromosome regions,
      entire chromosome arms, or entire chromosomes via fluorescence in situ
      hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial
      artificial chromosomes (BAC) from the target species or from a closely related
      species (comparative chromosome painting, CCP) are typically applied as painting
      probes. Extended pachytene chromosomes provide the highest resolution of CP in
      plants. CP enables identification and tracing of particular chromosome regions
      and/or entire chromosomes throughout all meiotic stages as well as corresponding
      chromosome territories in premeiotic interphase nuclei. Meiotic pairing and
      structural chromosome rearrangements (typically inversions and translocations)
      can be identified by CP. Here, we describe step-by-step protocols of CP and CCP
      in plant species including chromosome preparation, BAC DNA labeling, and
      multicolor FISH.

PMID- 23559199
TI  - Using sequential fluorescence and genomic in situ hybridization (FISH and GISH)
      to distinguish the A and C genomes in Brassica napus.
AB  - We have developed a sequential procedure with fluorescence in situ hybridization
      (FISH) and genomic in situ hybridization (GISH) that enables us to distinguish
      between the A and C genomes in Brassica napus and to identify certain individual
      chromosomes or chromosome groups within a genome. Our modified GISH technique
      uses a repetitive sequence in addition to the whole genome in the blocking DNA,
      and it is effective on meiotic and mitotic cells present in the anther material
      that we use.

PMID- 23559200
TI  - Labeling meiotic chromosomes in maize with fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) can be used to visualize chromosomal
      features using repetitive or single gene probes above a minimum target size. When
      applied to meiosis, each chromosome of the karyotypic complement can be
      identified, which can facilitate an understanding of the interrelationship of
      different chromosomes during this process. On the other hand, the pachytene stage
      of early meiosis is characterized by slightly but not strongly condensed
      chromosomes that permit more detailed analyses of adjacent features than can be
      achieved with somatic metaphase chromosomes.

PMID- 23559201
TI  - Examining female meiocytes of maize by confocal microscopy.
AB  - Meiosis is a key step in sexual plant reproduction. Cytological analysis of
      meiosis enables hypotheses of gene function during meiosis to be confirmed or
      discarded. Observation of meiosis in the female reproductive organs in many
      higher plants is technically challenging because the cells are enclosed deep
      within the nucellus and ovule tissues. In this chapter, we describe a simple
      staining procedure using Schiff's reagent optimized for use with confocal
      microscopy to observe meiosis within intact ovules of Zea mays (maize). Using
      this procedure we present images taken by confocal laser scanning microscopy of
      wild-type meiotic cells in whole-mount maize ovules.

PMID- 23559202
TI  - Three-dimensional acrylamide fluorescence in situ hybridization for plant cells.
AB  - Plant meiosis involves complex and dynamic processes that occur within the space
      inside the nucleus. Direct inspection of meiotic chromosomes by fluorescence
      microscopy has been used to investigate many of these processes. In particular,
      optical sectioning microscopy of fluorescence in situ hybridization (FISH)
      stained nuclei provides three-dimensional spatial information about the
      organization and distribution of specific sequences and chromosomal loci within
      the nucleus. Here we provide a fully detailed three-dimensional (3D) acrylamide
      FISH method for the analysis of plant meiotic nuclei. Several examples illustrate
      the versatility of this technique for the investigation of meiotic telomere
      dynamics in maize, Arabidopsis, and oat. Additional examples of 3D FISH include
      chromosome painting in a maize chromosome-addition line of oat and telomere FISH
      with maize nuclei from plants expressing a fluorescently tagged fusion protein,
      histone H2B-mCherry.

PMID- 23559203
TI  - Analyzing maize meiotic chromosomes with super-resolution structured illumination
      microscopy.
AB  - The success of meiosis depends on intricate coordination of a series of unique
      cellular processes to ensure proper chromosome segregation. Many proteins
      involved in these cellular events are directly or indirectly associated with
      chromosomes, especially those required for homologous recombination. These
      meiotic processes have been explored extensively by conventional light
      microscopy. However, many features of interest, such as chromatin organization,
      recombination nodules, or the synaptonemal complex are beyond the resolution of
      conventional wide-field microscopy. Moreover, in most sample preparation
      techniques for light microscopy, meiotic cells are squashed, which destroys the
      spatial organization of the nucleus. Here, I describe a protocol to analyze maize
      meiotic chromosomes by three-dimensional structured illumination microscopy (3D
      SIM), a recently developed high-resolution microscopy technique. This protocol
      can be used to examine protein localizations at a high resolution level by
      immunofluorescence.

PMID- 23559204
TI  - Live imaging of chromosome dynamics.
AB  - Progression of meiosis has been traditionally reconstructed from microscopic
      images collected from fixed cells. However, studies conducted in a number of
      species, including plants, indicate that this approach has clear shortcomings in
      accurately portraying the dynamic nature of meiotic processes. Here, we describe
      two methods to study chromosome dynamics in live meiocytes in maize, a protocol
      to observe chromosomes during meiotic prophase I and a technique to monitor
      chromosome segregation in anaphase I and anaphase II. The first method relies on
      culturing intact maize anthers and observing meiocytes embedded in the anthers
      with multiphoton excitation (MPE) microscopy. This approach circumvents
      difficulties in culturing isolated prophase I meiocytes in plants. The second
      technique uses culturing isolated meiocytes, which is possible with anaphase
      cells. Both methods can be fairly easily adapted for use in other plant species.
      We also detail the kinds of time-lapse movies that can be captured and analyzed
      using this technique, and describe software that can be utilized for analysis of
      movies chromosome dynamic in live meiocytes.

PMID- 23559205
TI  - Immunolocalization of meiotic proteins in Brassicaceae: method 1.
AB  - Plant meiosis studies have enjoyed a fantastic boom in recent years with the use
      of Arabidopsis thaliana as an important model species for developmental studies
      because of its small genome, short life cycle, and large mutant collections.
      Unlike other eukaryotic models, plant meiosis does not display strict checkpoints
      and rarely commits to apoptotic processes, which makes it possible to investigate
      the whole meiotic process (spanning from premeiotic interphase to spore
      formation) in knockout mutants. In this chapter we describe a protocol for
      immunolabelling Arabidopsis and Brassica meiotic proteins on robustly spread
      chromosomes. This protocol allows the detection of a large range of proteins on
      well-preserved chromosomes and throughout the entire meiotic process.

PMID- 23559206
TI  - Immunolocalization of meiotic proteins in Arabidopsis thaliana: method 2.
AB  - Advances in the molecular biology and genetics of Arabidopsis thaliana have led
      to it becoming an important model for the analysis of meiosis in plants.
      Cytogenetic investigations are pivotal to meiotic studies and a number of
      technological improvements for Arabidopsis cytology have provided a range of
      tools to investigate chromosome behavior during meiosis (Jones et al. Chromosome
      Res 11:205-215, 2003). This chapter contains a detailed description of an
      immunological technique currently used in our lab for the preparation of meiotic
      chromosomes for immunolocalization.

PMID- 23559207
TI  - Immunolocalization protocols for visualizing meiotic proteins in Arabidopsis
      thaliana: method 3.
AB  - Immunolocalization studies to visualize the distribution of proteins on meiotic
      chromosomes have become an integral part of studies on meiosis in the model
      organism Arabidopsis thaliana. This chapter describes fixation, sample
      preparation, and immunolocalization techniques used in our laboratory. These
      techniques have been used to visualize a wide range of meiotic proteins involved
      in different aspects of meiosis, including sister chromatid cohesion,
      recombination, synapsis, and chromosome segregation.

PMID- 23559208
TI  - A time course for the analysis of meiotic progression in Arabidopsis thaliana.
AB  - We have developed a technique that enables the thymidine analogues
      bromodeoxyuridine (BrdU) or ethynyldeoxyuridine (EdU) to be taken up via the
      transpiration stream into pollen mother cells and incorporated into the meiotic S
      phase. Labelled inflorescences are sampled at intervals, which enables assessment
      of the progression of labelled meiocytes by detection of the incorporated BrdU or
      EdU.

PMID- 23559209
TI  - Analyzing meiotic chromosomes in rice.
AB  - Development of techniques to analyze pachytene chromosomes has greatly overcome
      most of the difficulties in cytological studies of rice chromosomes caused by
      their small size. Visualization of meiotic chromosomes has now become routine in
      cytogenetic studies in this species. This chapter provides protocols on basic
      meiotic chromosome preparation, FISH analysis, and immunocytology in rice.

PMID- 23559210
TI  - Analyzing meiosis in barley.
AB  - This chapter contains a detailed description of the immunological and cytological
      techniques developed to determine factors involved in crossover control during
      meiosis in barley. The immunological technique involves digesting fresh anthers
      followed by chromosome spreading to remove cytoplasm that causes unwanted
      background, whilst protecting the fragile chromosome structure from being
      compromised. Specific antibodies raised against meiotic proteins are then
      incubated with nuclei, detected with secondary antibodies conjugated to
      fluorescent dyes, and visualized with either wide-field or confocal microscopes.
      In the cytological technique, barley inflorescences are fixed, followed by
      dissecting out the anthers, digesting the cell walls and then spreading the
      meiotic chromosomes. Both techniques can be used in conjunction with specific DNA
      probes for fluorescent in situ hybridization (FISH) to label telomeres,
      centromeres, and ribosomal DNA; to identify DNA modifications such as 5
      methylcytosine; and to detect the incorporation of DNA base analogues such as 5
      bromo-2'-deoxyuridine (BrdU) or 5-ethynyl-2'-deoxyuridine (EdU) to be used for a
      meiotic time-course or assaying newly synthesized DNA. Although these techniques
      have been specifically developed for barley, they should be directly transferable
      to other cereal crop species such as wheat and rice.

PMID- 23559211
TI  - Preparing SC spreads with RNs for EM analysis.
AB  - Recombination nodules (RNs) are associated with synaptonemal complexes (SCs)
      during early prophase I of meiosis. RNs are too small to be resolved by light
      microscopy and can be observed directly only by electron microscopy. The patterns
      of RNs on SCs can be analyzed using three-dimensional reconstructions of nuclei
      using serial thin sections, but this method is time consuming and technically
      difficult. In contrast, spreads of SCs are in one plane so all RNs in each set
      can be visualized simultaneously, and the patterns of both early and late nodules
      (ENs and LNs) can be analyzed far more easily than using sections. Here, we
      describe methods for preparing spreads of SCs and RNs from tomato primary
      microsporocytes on plastic-coated slides for visualization by transmission
      electron microscopy (TEM).

PMID- 23559212
TI  - Analysis of the synaptonemal complex in Brassica using TEM.
AB  - Much of meiosis research is focussed on Arabidopsis thaliana, largely due to the
      significant advantages it brings, having a small sequenced genome with
      comparatively little repetitive DNA, the ease of forward and reverse genetics,
      and a short life cycle. On the other hand, due the small genome size using
      Arabidopsis may be problematic for generating sufficient meiotic material for
      other types of analysis e.g., proteomics using prophase meiocytes and cytological
      analysis of the synaptonemal complex at the subcellular level. One solution is to
      use closely related species with larger genomes, in this case the Brassicas. This
      chapter contains methods for spreading of Brassica oleracea meiocytes for the
      analysis of the synaptonemal complex by silver staining and immunolocalization
      with gold-coupled antibodies using transmission electron microscopy.

PMID- 23559213
TI  - Preparing thin sections of meiotic nuclei for transmission electron microscopy.
AB  - Transmission electron microscopy (TEM) of thin sections of meiocytes embedded in
      plastic resin allows analysis of structures in meiotic nuclei, such as the
      synaptonemal complex, at very high resolution while preserving the spatial
      organization of chromosomes.

PMID- 23559214
TI  - Characterization of meiotic non-crossover molecules from Arabidopsis thaliana
      pollen.
AB  - Meiotic recombination is essential for proper segregation of homologous
      chromosomes and thus for formation of viable gametes. Recombination generates
      either crossovers (COs), which are reciprocal exchanges between chromosome
      segments, or gene conversion not associated with crossovers (NCOs). Both kinds of
      events occur in narrow regions (less than 10 kb) called hotspots, which are
      distributed along chromosomes. While NCOs may represent a large fraction of
      meiotic recombination events in plants, as in many other higher eukaryotes, they
      have been poorly characterized due to the technical difficulty of detecting them.
      Here, we present a powerful approach, based on allele-specific PCR amplification
      of single molecules from pollen genomic DNA, allowing detection, quantification
      and characterization of NCO events arising at low frequencies at recombination
      hotspots.

PMID- 23559215
TI  - Chromatin immunoprecipitation for studying chromosomal localization of meiotic
      proteins in maize.
AB  - Chromatin immunoprecipitation (ChIP) is a method that allows identification of
      chromosomal sites occupied by specific proteins. In this technique, chromatin is
      extracted from cells, sheared, and, using a specific antibody, enriched in
      fragments that contain a protein of interest. Genomic location of the protein can
      then be identified by hybridization of the resulting DNA to tiling microarrays or
      by sequencing. Thanks to advances in high-throughput sequencing methods, studying
      protein localization using ChIP has become possible even in species with
      relatively large genomes. Here, we describe a ChIP protocol that we developed to
      examine localization of meiotic proteins in maize.

PMID- 23559216
TI  - Analyzing the meiotic transcriptome using isolated meiocytes of Arabidopsis
      thaliana.
AB  - Improved transcriptome sequencing technologies (RNA-seq) have advanced our
      understanding of the tissue-specific transcriptome landscapes, including those of
      messenger RNAs, noncoding RNAs and small RNAs. However, transcriptome profiles of
      plant meiocytes remain challenging due to the lack of efficient methods to enrich
      meiocytes for the analysis of temporal and spatial gene expression patterns
      during meiosis. In this chapter, we describe a method to analyze the Arabidopsis
      meiotic transcriptome using isolated male meiocytes.

PMID- 23559217
TI  - Analysis of meiotic protein complexes from Arabidopsis and Brassica using
      affinity-based proteomics.
AB  - The application of proteomics techniques to the study of plant meiosis has the
      potential to make a valuable contribution to our understanding of the molecular
      events underpinning meiotic processes. Here we describe the preparation of
      meiotic protein complexes from Arabidopsis thaliana and its close crop relative,
      Brassica oleracea, by co-immunoprecipitation for in-solution analysis by tandem
      mass spectrometry (MS/MS). Early results using these techniques have proved
      encouraging, enabling the identification of candidate AtASY1-interacting proteins
      in A. thaliana and providing evidence of an in planta interaction between BoASY1
      and BoASY3 in B. oleracea. The detection of phospho-modified peptides of BoASY1
      and BoASY3 suggests that this approach may be useful for studying meiotic protein
      modification events.

PMID- 23559218
TI  - Identifying meiotic mutants in Arabidopsis thaliana.
AB  - Arabidopsis is a very powerful tool for understanding meiosis in plants with
      genetic approaches. We provide here a simple summary of the techniques used to
      test if a candidate gene has an essential meiotic function. These protocols
      require no specific prior knowledge and help eliminate easily avoided mistakes in
      the attribution of a meiotic function to your favorite gene.

PMID- 23559219
TI  - Effects of prenatal exposure to atypical antipsychotics on postnatal development
      and growth of infants: a case-controlled, prospective study.
AB  - OBJECTIVE: This study aims to investigate the developmental effects of atypical
      antipsychotics on infants who were born to mothers taking an atypical
      antipsychotic throughout pregnancy. METHOD: The developmental progress of 76
      infants who experienced fetal exposure to atypical antipsychotics was compared to
      that of 76 matched control infants who had no fetal exposure to any
      antipsychotics. Planned assessment included Apgar score, body weight, height, and
      the cognitive, language, motor, social-emotional, and adaptive behavior composite
      scores of the Bayley Scales of Infant and Toddler Development, third edition
      (BSID-III). Student's t test and Chi-square analysis were used as appropriate.
      Repeated measurements were evaluated by analysis of covariance. RESULTS: At 2
      months of age, the mean composite scores of cognitive, motor, social-emotional,
      and adaptive behavior of BSID-III were significantly lower in atypical
      antipsychotic-exposed infants than the controls. More atypical antipsychotic
      exposed infants had delayed development in cognitive, motor, social-emotional,
      and adaptive behavior domains as defined by the composite score of <85 in these
      subscales of BSID-III. At 12 months of age, there were no significant differences
      between the two groups in all mean composite scores of BSID-III. More atypical
      antipsychotic-exposed infants had low birth weight than the controls (13.2 vs.
      2.6 %, P = 0.031), although there were no significant difference in mean birth
      weight and height between the two groups. CONCLUSION: Fetal exposure to atypical
      antipsychotics may cause short-term delayed development in cognitive, motor,
      social-emotional, and adaptive behavior, but not in language, body weight, or
      height.

PMID- 23559221
TI  - Glucose and memory: the influence of drink, expectancy, and beliefs.
AB  - RATIONALE: An increasing number of studies suggest that glucose can enhance
      aspects of memory and the central methodology is the use of the glucose-placebo
      design. One critical issue therefore is separating the pharmacological effects of
      glucose from the expectancies created by consuming a drink that might contain
      glucose. OBJECTIVE: A modified balanced placebo design examined the role that
      expectancy and belief about the drink consumed has on the pharmacological changes
      observed following glucose consumption. METHOD: Ninety-three participants,
      allocated according to a drink (glucose, placebo) * message (told glucose, told
      nothing, told placebo) unrelated design, were administered tasks assessing
      immediate and delayed verbal free recall, spatial recognition and semantic
      verification. Each task has some evidence for hippocampus involvement, and
      variations in task difficulty were used to assess the idea that glucose effects
      are sensitive to task difficulty. RESULTS: While the messages biased drink
      judgements in the expected direction, judgements of drink content were at chance
      and glucose only enhanced delayed free recall. The subtle effects of the messages
      did not modify the glucose enhancement. However, believing glucose had been
      consumed showed an independent improvement in delayed free recall. There was no
      evidence that task complexity enhanced the glucose effect. CONCLUSIONS: The
      findings indicate that expectancy effects are unlikely to be confused with
      glucose enhancements, but beliefs about consuming glucose can augment performance
      on delayed free recall. The discussion considers the hippocampus and complexity
      hypotheses of glucose's mode of action and proposes the routine collection of
      drink beliefs in future studies.

PMID- 23559220
TI  - A randomized, 12-week study of the effects of extended-release paliperidone
      (paliperidone ER) and olanzapine on metabolic profile, weight, insulin
      resistance, and beta-cell function in schizophrenic patients.
AB  - OBJECTIVE: To compare matched paliperidone-ER- and olanzapine-treated
      schizophrenic patients on measures of glucose and lipid metabolism. METHODS:
      Eighty hospitalized patients with schizophrenia (DSM-IV) were randomly assigned
      to treatment with paliperidone ER or olanzapine for a period of 12 weeks. At
      baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip
      circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol,
      triglycerides, high density lipoprotein (HDL) cholesterol, low density
      lipoprotein (LDL) cholesterol, and prolactin. We also assessed at every time
      point body mass index (BMI), homeostasis insulin resistance (HOMA-IR), and
      homeostasis beta-cell function (HOMA-B). RESULTS: Thirty-three patients randomly
      assigned to paliperidone ER and 23 patients randomly assigned to olanzapine
      groups completed the entire 12-week treatment. Within-group analyses showed that
      fasting measures in both groups increased for weight, BMI, waist circumferences,
      hip circumference, subcutaneous fat, cholesterol, triglycerides, and prolactin.
      In contrast, fasting glucose, LDL, and HOMA-B increased during treatment only in
      the olanzapine group. We also detected significantly different serum prolactin
      levels at all time point between the paliperidone ER- and olanzapine-treated
      groups, as well as a statistical trend for HOMA-B to increase more in the
      olanzapine compared to paliperidone-ER group over the 12 weeks of the trial. We
      did not detect, however, differential drug effects over the 12 weeks of the trial
      on fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL,
      cholesterol, triglyceride, or HOMA-IR. CONCLUSION: This study reinforces the
      necessity of regularly monitoring metabolic parameters in patients with
      schizophrenia taking atypical antipsychotics, including paliperidone ER.

PMID- 23559223
TI  - Climate change conversations.

PMID- 23559228
TI  - Emerging diseases. New coronavirus reveals some of its secrets.

PMID- 23559222
TI  - Norepinephrine and impulsivity: effects of acute yohimbine.
AB  - RATIONALE: Rapid-response impulsivity, characterized by inability to withhold
      response to a stimulus until it is adequately appraised, is associated with risky
      behavior and may be increased in a state-dependent manner by norepinephrine.
      OBJECTIVE: We assessed effects of yohimbine, which increases norepinephrine
      release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine
      metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid
      response impulsivity. METHODS: Subjects were 23 healthy controls recruited from
      the community, with normal physical examination and ECG, and negative history for
      hypertension, cardiovascular illness, and axis I or II disorder. Blood pressure,
      pulse, and behavioral measures were obtained before and periodically after 0.4
      mg/kg oral yohimbine or placebo in a randomized, counterbalanced design.
      Metabolites of norepinephrine [3-methoxy-4-hydroxyphenylglycol (MHPG) and
      vanillylmandelic acid (VMA)] and dopamine [homovanillic acid (HVA)] were measured
      by high-pressure liquid chromatography with electrochemical detection. Rapid
      response impulsivity was measured by commission errors and reaction times on the
      immediate memory task (IMT), a continuous performance test designed to measure
      impulsivity and attention. RESULTS: Yohimbine increased plasma MHPG and VMA but
      not HVA. Yohimbine increased systolic and diastolic blood pressure and pulse
      rate. On the IMT, yohimbine increased impulsive errors and impulsive response
      bias and accelerated reaction times. Yohimbine-associated increase in plasma MHPG
      correlated with increased impulsive response rates. Time courses varied; effects
      on blood pressure generally preceded those on metabolites and test performance.
      CONCLUSIONS: These effects are consistent with increased rapid-response
      impulsivity after pharmacological noradrenergic stimulation in healthy controls.
      Labile noradrenergic responses, or increased sensitivity to norepinephrine, may
      increase risk for impulsive behavior.

PMID- 23559229
TI  - Species extinction. Fluttering from the ashes?

PMID- 23559230
TI  - Neuroscience. How to build a dream-reading machine.

PMID- 23559231
TI  - The deep Earth machine is coming together.

PMID- 23559232
TI  - Molecular biology. 'Dead' enzymes show signs of life.

PMID- 23559233
TI  - Dead or alive?

PMID- 23559235
TI  - Genomics. What if extinction is not forever?

PMID- 23559236
TI  - Ecology. Dynamics of coral reef recovery.

PMID- 23559237
TI  - Neuroscience. A trace of your place.

PMID- 23559238
TI  - Physiology. The perfect hypnotic?

PMID- 23559239
TI  - Microbiology. Breathing perchlorate.

PMID- 23559240
TI  - Developmental biology. Programmed cell death in neuronal development.

PMID- 23559241
TI  - Chemistry. Revealing the positive side of fluorine.

PMID- 23559242
TI  - Astronomy. Modeling the solar dynamo.

PMID- 23559243
TI  - A tissue-like printed material.
AB  - Living cells communicate and cooperate to produce the emergent properties of
      tissues. Synthetic mimics of cells, such as liposomes, are typically incapable of
      cooperation and therefore cannot readily display sophisticated collective
      behavior. We printed tens of thousands of picoliter aqueous droplets that become
      joined by single lipid bilayers to form a cohesive material with cooperating
      compartments. Three-dimensional structures can be built with heterologous
      droplets in software-defined arrangements. The droplet networks can be
      functionalized with membrane proteins; for example, to allow rapid electrical
      communication along a specific path. The networks can also be programmed by
      osmolarity gradients to fold into otherwise unattainable designed structures.
      Printed droplet networks might be interfaced with tissues, used as tissue
      engineering substrates, or developed as mimics of living tissue.

PMID- 23559244
TI  - Broadband 2D electronic spectroscopy reveals a carotenoid dark state in purple
      bacteria.
AB  - Although the energy transfer processes in natural light-harvesting systems have
      been intensively studied for the past 60 years, certain details of the underlying
      mechanisms remain controversial. We performed broadband two-dimensional (2D)
      electronic spectroscopy measurements on light-harvesting proteins from purple
      bacteria and isolated carotenoids in order to characterize in more detail the
      excited-state manifold of carotenoids, which channel energy to
      bacteriochlorophyll molecules. The data revealed a well-resolved signal
      consistent with a previously postulated carotenoid dark state, the presence of
      which was confirmed by global kinetic analysis. The results point to this state's
      role in mediating energy flow from carotenoid to bacteriochlorophyll.

PMID- 23559245
TI  - Evidence for a symmetrical fluoronium ion in solution.
AB  - Halonium ions, in which formally positively charged halogens (chlorine, bromine,
      and iodine) are equivalently attached to two carbon atoms through three-center
      bonds, are well established in the synthetic chemistry of organochlorides,
      bromides, and iodides. Mechanistic studies of these ions have generated numerous
      insights into the origins of stereoselectivity in addition and displacement
      reactions. However, it has not been clear whether fluorine can form a halonium
      ion in the same manner. We present chemical and theoretical evidence for the
      transient generation of a true symmetrical fluoronium ion in solution from an
      appropriately configured precursor.

PMID- 23559246
TI  - Europe-wide dampening of population cycles in keystone herbivores.
AB  - Suggestions of collapse in small herbivore cycles since the 1980s have raised
      concerns about the loss of essential ecosystem functions. Whether such phenomena
      are general and result from extrinsic environmental changes or from intrinsic
      process stochasticity is currently unknown. Using a large compilation of time
      series of vole abundances, we demonstrate consistent cycle amplitude dampening
      associated with a reduction in winter population growth, although regulatory
      processes responsible for cyclicity have not been lost. The underlying syndrome
      of change throughout Europe and grass-eating vole species suggests a common
      climatic driver. Increasing intervals of low-amplitude small herbivore population
      fluctuations are expected in the future, and these may have cascading impacts on
      trophic webs across ecosystems.

PMID- 23559247
TI  - Recovery of an isolated coral reef system following severe disturbance.
AB  - Coral reef recovery from major disturbance is hypothesized to depend on the
      arrival of propagules from nearby undisturbed reefs. Therefore, reefs isolated by
      distance or current patterns are thought to be highly vulnerable to catastrophic
      disturbance. We found that on an isolated reef system in north Western Australia,
      coral cover increased from 9% to 44% within 12 years of a coral bleaching event,
      despite a 94% reduction in larval supply for 6 years after the bleaching. The
      initial increase in coral cover was the result of high rates of growth and
      survival of remnant colonies, followed by a rapid increase in juvenile
      recruitment as colonies matured. We show that isolated reefs can recover from
      major disturbance, and that the benefits of their isolation from chronic
      anthropogenic pressures can outweigh the costs of limited connectivity.

PMID- 23559248
TI  - Decameric SelA*tRNA(Sec) ring structure reveals mechanism of bacterial
      selenocysteine formation.
AB  - The 21st amino acid, selenocysteine (Sec), is synthesized on its cognate transfer
      RNA (tRNA(Sec)). In bacteria, SelA synthesizes Sec from Ser-tRNA(Sec), whereas in
      archaea and eukaryotes SepSecS forms Sec from phosphoserine (Sep) acylated to
      tRNA(Sec). We determined the crystal structures of Aquifex aeolicus SelA
      complexes, which revealed a ring-shaped homodecamer that binds 10 tRNA(Sec)
      molecules, each interacting with four SelA subunits. The SelA N-terminal domain
      binds the tRNA(Sec)-specific D-arm structure, thereby discriminating Ser
      tRNA(Sec) from Ser-tRNA(Ser). A large cleft is created between two subunits and
      accommodates the 3'-terminal region of Ser-tRNA(Sec). The SelA structures
      together with in vivo and in vitro enzyme assays show decamerization to be
      essential for SelA function. SelA catalyzes pyridoxal 5'-phosphate-dependent Sec
      formation involving Arg residues nonhomologous to those in SepSecS. Different
      protein architecture and substrate coordination of the bacterial enzyme provide
      structural evidence for independent evolution of the two Sec synthesis systems
      present in nature.

PMID- 23559249
TI  - Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of
      Su(var)3-9.
AB  - Eukaryotic genomes harbor transposable elements and other repetitive sequences
      that must be silenced. Small RNA interference pathways play a major role in their
      repression. Here, we reveal another mechanism for silencing these sequences in
      Drosophila. Depleting the linker histone H1 in vivo leads to strong activation of
      these elements. H1-mediated silencing occurs in combination with the
      heterochromatin-specific histone H3 lysine 9 methyltransferase Su(var)3-9. H1
      physically interacts with Su(var)3-9 and recruits it to chromatin in vitro, which
      promotes H3 methylation. We propose that H1 plays a key role in silencing by
      tethering Su(var)3-9 to heterochromatin. The tethering function of H1 adds to its
      established role as a regulator of chromatin compaction and accessibility.

PMID- 23559250
TI  - Translational repression and eIF4A2 activity are critical for microRNA-mediated
      gene regulation.
AB  - MicroRNAs (miRNAs) control gene expression through both translational repression
      and degradation of target messenger RNAs (mRNAs). However, the interplay between
      these processes and the precise molecular mechanisms involved remain unclear.
      Here, we show that translational inhibition is the primary event required for
      mRNA degradation. Translational inhibition depends on miRNAs impairing the
      function of the eIF4F initiation complex. We define the RNA helicase eIF4A2 as
      the key factor of eIF4F through which miRNAs function. We uncover a correlation
      between the presence of miRNA target sites in the 3' untranslated region (3'UTR)
      of mRNAs and secondary structure in the 5'UTR and show that mRNAs with
      unstructured 5'UTRs are refractory to miRNA repression. These data support a
      linear model for miRNA-mediated gene regulation in which translational repression
      via eIF4A2 is required first, followed by mRNA destabilization.

PMID- 23559251
TI  - Archaeal (per)chlorate reduction at high temperature: an interplay of biotic and
      abiotic reactions.
AB  - Perchlorate and chlorate anions [(per)chlorate] exist in the environment from
      natural and anthropogenic sources, where they can serve as electron acceptors for
      bacteria. We performed growth experiments combined with genomic and proteomic
      analyses of the hyperthermophile Archaeoglobus fulgidus that show (per)chlorate
      reduction also extends into the archaeal domain of life. The (per)chlorate
      reduction pathway in A. fulgidus relies on molybdo-enzymes that have similarity
      with bacterial enzymes; however, chlorite is not enzymatically split into
      chloride and oxygen. Evidence suggests that it is eliminated by an interplay of
      abiotic and biotic redox reactions involving sulfur compounds. Biological
      (per)chlorate reduction by ancient archaea at high temperature may have prevented
      accumulation of perchlorate in early terrestrial environments and consequently
      given rise to oxidizing conditions on Earth before the rise of oxygenic
      photosynthesis.

PMID- 23559252
TI  - Influence of HLA-C expression level on HIV control.
AB  - A variant upstream of human leukocyte antigen C (HLA-C) shows the most
      significant genome-wide effect on HIV control in European Americans and is also
      associated with the level of HLA-C expression. We characterized the differential
      cell surface expression levels of all common HLA-C allotypes and tested directly
      for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals.
      Increasing HLA-C expression was associated with protection against multiple
      outcomes independently of individual HLA allelic effects in both African and
      European Americans, regardless of their distinct HLA-C frequencies and linkage
      relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with
      increased likelihood of cytotoxic T lymphocyte responses and frequency of viral
      escape mutation. In contrast, high HLA-C expression had a deleterious effect in
      Crohn's disease, suggesting a broader influence of HLA expression levels in human
      disease.

PMID- 23559254
TI  - Rats and humans can optimally accumulate evidence for decision-making.
AB  - The gradual and noisy accumulation of evidence is a fundamental component of
      decision-making, with noise playing a key role as the source of variability and
      errors. However, the origins of this noise have never been determined. We
      developed decision-making tasks in which sensory evidence is delivered in
      randomly timed pulses, and analyzed the resulting data with models that use the
      richly detailed information of each trial's pulse timing to distinguish between
      different decision-making mechanisms. This analysis allowed measurement of the
      magnitude of noise in the accumulator's memory, separately from noise associated
      with incoming sensory evidence. In our tasks, the accumulator's memory was
      noiseless, for both rats and humans. In contrast, the addition of new sensory
      evidence was the primary source of variability. We suggest our task and modeling
      approach as a powerful method for revealing internal properties of decision
      making processes.

PMID- 23559253
TI  - Transposition-driven genomic heterogeneity in the Drosophila brain.
AB  - Recent studies in mammals have documented the neural expression and mobility of
      retrotransposons and have suggested that neural genomes are diverse mosaics. We
      found that transposition occurs among memory-relevant neurons in the Drosophila
      brain. Cell type-specific gene expression profiling revealed that transposon
      expression is more abundant in mushroom body (MB) alphabeta neurons than in
      neighboring MB neurons. The Piwi-interacting RNA (piRNA) proteins Aubergine and
      Argonaute 3, known to suppress transposons in the fly germline, are expressed in
      the brain and appear less abundant in alphabeta MB neurons. Loss of piRNA
      proteins correlates with elevated transposon expression in the brain. Paired-end
      deep sequencing identified more than 200 de novo transposon insertions in
      alphabeta neurons, including insertions into memory-relevant loci. Our
      observations indicate that genomic heterogeneity is a conserved feature of the
      brain.

PMID- 23559255
TI  - Optogenetic dissection of entorhinal-hippocampal functional connectivity.
AB  - We used a combined optogenetic-electrophysiological strategy to determine the
      functional identity of entorhinal cells with output to the place-cell population
      in the hippocampus. Channelrhodopsin-2 (ChR2) was expressed selectively in the
      hippocampus-targeting subset of entorhinal projection neurons by infusing
      retrogradely transportable ChR2-coding recombinant adeno-associated virus in the
      hippocampus. Virally transduced ChR2-expressing cells were identified in medial
      entorhinal cortex as cells that fired at fixed minimal latencies in response to
      local flashes of light. A large number of responsive cells were grid cells, but
      short-latency firing was also induced in border cells and head-direction cells,
      as well as cells with irregular or nonspatial firing correlates, which suggests
      that place fields may be generated by convergence of signals from a broad
      spectrum of entorhinal functional cell types.

PMID- 23559256
TI  - Optimized quantification of diffusional non-gaussianity in the human brain.
AB  - PURPOSE: To test the performance of three existing models of diffusional non
      Gaussianity and introduce a new model. MATERIALS AND METHODS: Quantitative
      measures of diffusional non-Gaussianity provide clinically useful information.
      Three-parameter mathematical models are particularly relevant, because they
      assign one parameter to non-Gaussianity, one to diffusivity and one to the signal
      in the absence of diffusion weighting. One such model is the cumulant expansion,
      where the logarithm of the signal is approximated by a Taylor series. Convergence
      may be blocked by singularities in the complex b-plane. To overcome this problem,
      we replace the Taylor series by a Pade approximant, which can model
      singularities. The resulting signal model is denoted the Pade exponent model.
      Analyzing diffusion-weighted brain data from four volunteers, we compare the
      performance of the Pade exponent model with the statistical model, the stretched
      exponential model and the cumulant expansion. With voxelwise hypothesis testing,
      we calculate the fraction of voxels where the models fail to describe the data.
      RESULTS: With 16 b-values in the range [0,5000] s/mm(2) , the fractions of
      rejected voxels in white / gray matter are: statistical model, 41 / 20%;
      stretched exponential model, 68 / 16.6%; cumulant expansion, 58 / 37%; Pade
      exponent, 5.2 / 16.1%. The parameters of the Pade exponent model do not depend
      strongly on the range of measured b-values. CONCLUSION: The Pade exponent model
      describes non-Gaussian diffusion data with high precision over a wide range of b
      values.

PMID- 23559258
TI  - Using waste Li ion batteries as cathodes in rechargeable Li-liquid batteries.
AB  - The rechargeable Li-liquid battery was developed using waste Li ion battery
      materials immersed in water and used as the liquid cathode. Either the Li metal
      or Li ions (by the formation LixC6 or Li(4+x)Ti5O12) was harvested from waste Li
      ion source materials such as a waste anode (LixC6), cathode (LixFePO4), and
      electrolyte (LiPF6 in EC:DEC) by charging the cell, which then discharged with
      the waste products in the liquid cathode solution to produce electric energy.
      When the Li4Ti5O12 was used as the anode with the waste products as the cathode
      in the proposed battery system, a good cycle-life with high coulombic efficiency
      was observed.

PMID- 23559257
TI  - Suppression of interactions between prostate tumor cell-surface integrin and
      endothelial ICAM-1 by simvastatin inhibits micrometastasis.
AB  - Cancer micrometastasis relies on the ability of cancer cells to secrete
      angiogenic modulators, to interact with the vascular endothelium, and to overcome
      the resistance offered by the endothelial-barrier. Being an essential step prior
      to metastasis, blockage of micrometastasis can have potential applications in
      cancer therapy and metastasis prevention. Due to poorly known molecular
      mechanisms leading to micrometastasis, developing therapeutic strategies to
      target prostate cancer utilizing drugs that block micrometastasis is far from
      reality. Here, we demonstrate the potential benefits of simvastatin in the
      inhibition of prostate cancer micrometastasis and reveal the novel molecular
      mechanisms underlying this process. First, we showed that simvastatin inhibited
      the ability of human PC3 prostate cancer cells for transendothelial migration in
      vitro. Second, our data indicated that simvastatin modulates the expression of
      tumor-derived factors such as angiopoietins and VEGF-A at the mRNA and protein
      levels by the PC3 cells, thus preventing endothelial-barrier disruption. Third,
      simvastatin directly activated endothelial cells and enhances endothelial-barrier
      resistance. Apart from this, our study revealed that simvastatin-mediated effect
      on PC3 micrometastasis was mediated through inhibition of integrin alphav beta3
      activity and suppression of interaction between prostate cancer cell integrin
      alphav beta3 with endothelial ICAM-1.

PMID- 23559259
TI  - [The surgeon and the metastatic disease].
AB  - For a long time, metastatic disease was a prohibited zone for surgeons locked
      into their roles in controlling primary non-disseminated tumours. However, this
      has changed at the end of the 20th century with the apparition of effective
      chemotherapies and targeted therapies. Since then, surgeons have been able to
      treat hepatic, pulmonary, peritoneal and brain metastases. The more chemotherapy
      progresses and controls disease, the more surgeons can operate on residual
      disease. With this final surgery acting on the defined perimeter of systemic
      treatment efficacy, it appears to offer gains in progression-free survival. Gains
      in overall survival have not yet been demonstrated. Further, new technologies
      should enable surgeons to reduce the lower limits of their fields of action,
      increasing their therapeutic perimeters. Metastatic disease constitutes a unique
      model of therapeutic synergy that can be accredited to multidisciplinary
      strategy.

PMID- 23559260
TI  - Alteration in abundance and compartmentalization of inflammation-related miRNAs
      in plasma after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: We tested the hypothesis that circulating microRNAs
      (miRNAs) present in plasma might display a specific signature in patients with
      intracerebral hemorrhage. METHODS: Global miRNA profiles were determined with the
      Agilent Human miRNA Microarray platform, and validated by quantitative polymerase
      chain reaction. RESULTS: A subset of 30 miRNAs were selectively upregulated in
      both male and female patients with intracerebral hemorrhage. Network analysis
      revealed that the most significantly overrepresented biological process
      associated with these miRNAs was inflammation. Unlike the plasma miRNAs in
      healthy controls, which were detected exclusively in the microvesicle fraction,
      the deregulated plasma miRNAs after intracerebral hemorrhage were present in both
      the microvesicle and the supernatant fractions. CONCLUSIONS: Intracerebral
      hemorrhage altered both the abundance and the compartmentalization of several
      inflammation-related miRNAs in plasma.

PMID- 23559262
TI  - Letter by Parakh regarding article, "cannabis-related stroke: myth or reality?".

PMID- 23559263
TI  - Evidence-based translational medicine.

PMID- 23559261
TI  - Heritability estimates identify a substantial genetic contribution to risk and
      outcome of intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Previous studies suggest that genetic variation plays a
      substantial role in occurrence and evolution of intracerebral hemorrhage (ICH).
      Genetic contribution to disease can be determined by calculating heritability
      using family-based data, but such an approach is impractical for ICH because of
      lack of large pedigree-based studies. However, a novel analytic tool based on
      genome-wide data allows heritability estimation from unrelated subjects. We
      sought to apply this method to provide heritability estimates for ICH risk,
      severity, and outcome. METHODS: We analyzed genome-wide genotype data for 791 ICH
      cases and 876 controls, and determined heritability as the proportion of
      variation in phenotype attributable to captured genetic variants. Contribution to
      heritability was separately estimated for the APOE (encoding apolipoprotein E)
      gene, an established genetic risk factor, and for the rest of the genome.
      Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day
      mortality. RESULTS: ICH risk heritability was estimated at 29% (SE, 11%) for non
      APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality
      was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on
      hematoma volume was also substantial: admission volume heritability was estimated
      at 60% (SE, 70%) for non-APOEloci and at 12% (SE, 4%) for APOE. CONCLUSIONS:
      Genetic variation plays a substantial role in ICH risk, outcome, and hematoma
      volume. Previously reported risk variants account for only a portion of inherited
      genetic influence on ICH pathophysiology, pointing to additional loci yet to be
      identified.

PMID- 23559264
TI  - ASTRAL score predicts 5-year dependence and mortality in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The ASTRAL score was externally validated showing
      remarkable consistency on 3-month outcome prognosis in patients with acute
      ischemic stroke. The present study aimed to evaluate ASTRAL score's prognostic
      accuracy to predict 5-year outcome. METHODS: All consecutive patients with acute
      ischemic stroke registered in the Athens Stroke Registry between January 1, 1998,
      and December 31, 2010, were included. Patients were excluded if admitted >24
      hours after symptom onset or if any ASTRAL score component was missing. End
      points were 5-year unfavorable functional outcome, defined as modified Rankin
      Scale 3 to 6, and 5-year mortality. For each outcome, the area under the receiver
      operating characteristics curve was calculated; also, a multivariate Cox
      proportional hazards analysis was performed to investigate whether the ASTRAL
      score was an independent predictor of outcome. The Kaplan-Meier product limit
      method was used to estimate the probability of 5-year survival for each ASTRAL
      score quartile. RESULTS: The area under the receiver operating characteristics
      curve of the score to predict 5-year unfavorable functional outcome was 0.89, 95%
      confidence interval 0.88 to 0.91. In multivariate Cox proportional hazards
      analysis, the ASTRAL score was independently associated with 5-year unfavorable
      functional outcome (hazard ratio, 1.09; 95% confidence interval, 1.08-1.10). The
      area under the receiver operating characteristics curve for the ASTRAL score's
      discriminatory power to predict 5-year mortality was 0.81 (95% confidence
      interval, 0.78-0.83). In multivariate analysis, the ASTRAL score was
      independently associated with 5-year mortality (hazard ratio, 1.09, 95%
      confidence interval, 1.08-1.10). During the 5-year follow-up, the probability of
      survival was significantly lower with increasing ASTRAL score quartiles (log-rank
      test <0.001). CONCLUSIONS: The ASTRAL score reliably predicts 5-year functional
      outcome and mortality in patients with acute ischemic stroke.

PMID- 23559265
TI  - Chronic pain syndromes after ischemic stroke: PRoFESS trial.
AB  - BACKGROUND AND PURPOSE: Chronic pain syndromes are reported to be common after
      stroke, but most previous epidemiological studies have generally included small
      cohorts of patients with relatively short-term follow-up. In a large cohort with
      ischemic stroke (Prevention Regimen for Effectively avoiding Second Stroke
      [PRoFESS] trial), we determined the prevalence, risk factors, and clinical
      consequence of new poststroke pain syndromes. METHODS: Within the PRoFESS trial
      (mean follow-up 2.5 years), a standardized chronic pain questionnaire was
      administered (at the penultimate follow-up visit) to all participants who
      reported chronic pain since their stroke and did not have a history of chronic
      pain before their index stroke. Multivariable logistic regression analyses were
      used to determine risk factors for poststroke pain (and pain subtypes), and the
      association between poststroke pain and cognitive (>= 3 reduction in Mini-Mental
      State Examination score) and functional decline (>= 1 increase in m-Rankin).
      RESULTS: In total, 15 754 participants were included; of which 1665 participants
      (10.6%) reported new chronic poststroke pain, and included 431 participants
      (2.7%) with central poststroke pain, 238 (1.5%) with peripheral neuropathic pain,
      208 (1.3%) with pain from spasticity, and 136 participants (0.9%) with pain from
      shoulder subluxation. More than 1 pain subtype was reported in 86 participants
      (0.6%). Predictors of poststroke pain included increased stroke severity, female
      sex, alcohol intake, statin use, depressive symptoms, diabetes mellitus,
      antithrombotic regimen, and peripheral vascular disease. A new chronic pain
      syndrome was associated with greater dependence (odds ratio, 2.16; 95% confidence
      interval, 1.82-2.56). Peripheral neuropathy and pain from spasticity/shoulder
      subluxation were associated with cognitive decline. CONCLUSIONS: Chronic pain
      syndromes are common after ischemic stroke and are associated with increased
      functional dependence and cognitive decline.

PMID- 23559266
TI  - Letter by Plas et al regarding article, "smoking-thrombolysis paradox:
      recanalization and reperfusion rates after intravenous tissue plasminogen
      activator in smokers with ischemic stroke".

PMID- 23559267
TI  - Combining antithrombotic and fibrinolytic agents: can it be done?

PMID- 23559268
TI  - Nuclear localization of the actin regulatory protein Palladin in sertoli cells.
AB  - In the testis, F-actin structures are involved in spermatid nuclear remodeling
      and cytoplasm reduction, maintenance of the blood-testis barrier, support of the
      spermatogonial stem cell niche, and release of spermatids into the tubular lumen.
      To gain a better understanding of actin regulation in Sertoli-germ cell
      interactions, we investigated the expression of the Palladin (Palld) gene, which
      encodes a widely expressed phosphoprotein that localizes to actin-rich
      cytoplasmic structures, including focal adhesions, cell-cell junctions,
      podosomes, and stress fibers, and serves as a molecular scaffold to bundle actin
      fibers. In germ cells, PALLD was concentrated along the tubulin- and F-actin
      containing cytoplasmic manchette that forms adjacent to the elongating spermatid
      nucleus during spermiogenesis. To our surprise, PALLD relocated from the
      cytoplasm to the nucleus of Sertoli cells in the juvenile testis, coincident with
      the onset of puberty, and this localization was maintained in the adult. We
      provide evidence that the 140 kDa isoform of PALLD predominates in Sertoli cells,
      and that it is apparently cleaved, with the C-terminus localizing to the nucleus
      while the N-terminus remains cytoplasmic. We investigated the nuclear
      localization of the C-terminus of PALLD and found that it is regulated by a
      putative nuclear export signal. These results provide the foundation for future
      work employing Sertoli cell- and spermatid-specific Palld-knockout mice to study
      diverse roles of PALLD as both a nuclear-actin regulatory protein and as a
      potential regulator of manchette formation during spermatogenesis.

PMID- 23559269
TI  - Prenatal presentation of fronto-orbital congenital infantile fibrosarcoma: a
      clinicopathologic report.

PMID- 23559270
TI  - Highly effective water oxidation catalysis with iridium complexes through the use
      of NaIO4.
AB  - Exceptional water oxidation (WO) turnover frequencies (TOF=17,000 h(-1)), and
      turnover numbers (TONs) close to 400,000, the largest ever reported for a metal
      catalyzed WO reaction, have been found by using [Cp*Ir(III)(NHC)Cl2] (in which
      NHC=3-methyl-1-(1-phenylethyl)-imidazoline-2-ylidene) as the pre-catalyst and
      NaIO4 as oxidant in water at 40  degrees C. The apparent TOF for
      [Cp*Ir(III)(NHC)X2] (1X, in which X stands for I (1I), Cl (1Cl), or triflate
      anion (1OTf)) and [(Cp*-NHCMe)Ir(III)I2] (2) complexes, is kept constant during
      almost all of the O2 evolution reaction when using NaIO4 as oxidant. The TOF was
      found to be dependent on the ligand and on the anion (TOF ranging from ~600 to
      ~1100 h(-1) at 25  degrees C). Degradation of the complexes by oxidation of the
      organic ligands upon reaction with NaIO4 has been investigated. (1)H NMR, ESI-MS,
      and dynamic light-scattering measurements (DLS) of the reaction medium indicated
      that the complex undergoes rapid degradation, even at low equivalents of oxidant,
      but this process takes place without formation of nanoparticles. Remarkably,
      three-month-old solution samples of oxidized pre-catalysts remain equally as
      active as freshly prepared solutions. A UV/Vis feature band at lambdamax =405 nm
      is observed in catalytic reaction solutions only when O2 evolves, which may be
      attributed to a resting state iridium speciation, most probably Ir-oxo species
      with an oxidation state higher than IV.

PMID- 23559271
TI  - Selective binding of 2'-F-c-di-GMP to Ct-E88 and Cb-E43, new class I riboswitches
      from Clostridium tetani and Clostridium botulinum respectively.
AB  - C-di-GMP is a second messenger in bacteria and partly regulates bacterial
      physiology by binding to class I and II riboswitches. Four class I c-di-GMP
      riboswitch aptamer candidates, Ct-E88, Cb-17B, Cb-E43 and Cd-630 RNAs, selected
      from a GEMM RNA sequence motif in the Rfam database, were expressed and
      experimentally verified to bind to c-di-GMP. The two newly characterized c-di-GMP
      riboswitches, Ct-E88 and Cb-E43, bound c-di-GMP with nanomolar Kd whereas the
      affinities of Cb-17B and Cd-630 for c-di-GMP were at least a 100-fold weaker.
      Interestingly, whereas the three riboswitches (Vc2, Et-E88 and Cb-E43) bound c-di
      GMP with similar Kd values, 2'-modified analogs of c-di-GMP differentially bound
      to these three class I aptamers. For example, 2'-F-c-di-GMP bound Vc2 with a Kd
      value of 102 nM whereas the Kd value of 2'-F-c-di-GMP-Ct-E88 is 43 MUM (422*
      higher than that for Vc2 RNA), revealing that there are differences in the
      binding sites of functional class I c-di-GMP riboswitches.

PMID- 23559272
TI  - Differential microRNAs expression in serum of patients with lung cancer,
      pulmonary tuberculosis, and pneumonia.
AB  - MicroRNAs (miRNAs) play critical regulatory roles in the physiological and
      pathological processes. The high stability of miRNAs in human serum represents
      attractive novel diagnostic biomarkers of clinical conditions. Several studies
      have shown that aberrant expression of miRNAs in human cancer including lung
      cancer, but little is known about their effects on some infectious lung diseases
      such as pulmonary tuberculosis (TB) and pneumonia. In this study, we investigated
      miRNA expression pattern in serum of Egyptian patients with lung cancer, TB, and
      pneumonia compared with matched healthy controls. Using microarray-based
      expression profiling followed by real-time quantitative polymerase chain reaction
      validation, we compared the levels of a series of circulating miRNAs (miR-21, miR
      155, miR-182, and miR-197) in serum from patients with lung cancer (n = 65),
      pulmonary tuberculosis (n = 29), pneumonia (n = 29), and transudate (n = 16)
      compared with matched healthy controls (n = 37). MiRNA SNORD68 was the
      housekeeping endogenous control. We found that the serum levels of miR-21, miR
      155, and miR-197 were significantly elevated in the patients with lung cancer and
      pneumonia whereas miR-182 and miR-197 levels were increased only in patients with
      lung cancer and TB, respectively, compared with controls. Receiver operating
      characteristic analysis revealed that miR-182, miR-155, and miR-197 have superior
      diagnostic potential in discriminating patients with lung cancer, pneumonia, and
      TB, respectively, from controls. Our results conclude that the differential
      expression of the four studied miRNAs can be potential non-invasive biomarkers
      for patients with lung cancer, TB and pneumonia.

PMID- 23559273
TI  - Verapamil reverses myocardial no-reflow after primary percutaneous coronary
      intervention in patients with acute myocardial infarction.
AB  - The present study evaluated the efficacy of intracoronary administration of
      verapamil to attenuate the no-reflow phenomenon following the primary
      percutaneous coronary intervention (PCI) in patients with the ST-segment
      elevation acute myocardial infarction (STEMI). A total of 201 patients with STEMI
      who underwent primary PCI within 12 h from the beginning of the heart attack were
      included. The no-reflow phenomenon was defined as substantial coronary
      anterograde flow of TIMI <=2. Verapamil (100-200 MUg) was injected into coronary
      artery immediately after no-reflow; the coronary arteriography was repeated
      later. Hundred and ninety-eight patients with STEMI successfully underwent
      primary PCI, and 246 stents were implanted with the average of 1.2 stents per
      patient. No-reflow occurred in 25 out of 198 patients (12.6%). Twenty-one (84%)
      patients developed the flow of TIMI >=3 after intracoronary administration of
      verapamil, as revealed by repeated coronary angiography. Two patients developed
      transient hypotension which normalized without treatment within 3-5 min. Three
      patients showed sinus bradycardia, in one patient there was transient II
      sinoatrial block, and one patient developed type 1 atrioventricular block. All
      adverse effects were alleviated after intravenous injection of atropine (0.5-1
      mg). In conclusion, the no-reflow phenomenon following primary PCI in patients
      with STEMI is significantly improved by intracoronary administration of verapamil
      which is useful to reduce cardiovascular events during operation.

PMID- 23559274
TI  - Obesity modulates the immune response to oxidized LDL in hypertensive patients.
AB  - Obesity and hypertension have been recognized as inflammatory diseases capable of
      activating the immune system, thus contributing to an increased cardiovascular
      risk. However, the link between adaptive immunity, obesity, and hypertension is
      poorly understood. We investigated the relationship of the body mass index (BMI)
      on the inflammatory, vascular, and immune responses in patients with hypertension
      naive of anti-hypertensive treatment. Hypertensive patients (N = 88) were divided
      into three groups: normal weight (NW), overweight (OW), and obese (OB) subjects.
      Anti-oxidized LDL autoantibodies (anti-oxLDL Abs), anti-ApoB-D peptide (anti-ApoB
      D) Abs, interleukin (IL)-8 and IL-10, flow-mediated dilation (FMD) of the
      brachial artery, and 24-h ambulatory blood pressure monitoring (ABPM) were
      assessed. OB patients presented lower levels of anti-oxLDL Abs and IL-10, higher
      levels of IL-8, and impaired FMD, when compared to NW and OW (P < 0.05), without
      differences between groups regarding anti-ApoB-D Abs. After adjusting for age,
      systolic and diastolic blood pressure, anti-oxLDL Abs were inversely correlated
      with BMI and waist circumference (r = -0.24, P = 0.02 and r = -0.25, P = 0.02,
      respectively), whereas ApoB-D correlated with 24-h ABPM (r = 0.22, P = 0.05 for
      systolic, and r = 0.29, P = 0.01 for diastolic blood pressure). Regression
      analyses showed inverse associations of anti-oxLDL Abs with BMI (beta = -0.05, P
      = 0.01) and waist circumference (beta = -0.01, P = 0.02); anti-ApoB-D Abs were
      associated with systolic and diastolic 24-h ABPM (beta = 0.96, P = 0.04; beta =
      1.02, P = 0.005, for systolic and diastolic 24-h ABPM, respectively). Among
      hypertensive patients, obesity modulates the immune and inflammatory milieu,
      determining an unfavorable balance of cytokines and reduction in titers of anti
      oxLDL Abs. Twenty-four hour ABPM is associated with titers of anti-ApoB-D Abs.

PMID- 23559275
TI  - Comparative study of 1,064-nm laser-induced skin burn and thermal skin burn.
AB  - Infrared lasers are widely used in medicine, industry, and other fields. While
      science, medicine, and the society in general have benefited from the many
      practical uses of lasers, they also have inherent safety issues. Although several
      procedures have been put forward to protect the skin from non-specific laser
      induced damage, individuals receiving laser therapy or researchers who use laser
      are still at risk for skin damage. This study aims to understand the interaction
      between laser and the skin, and to investigate the differences between the skin
      damage caused by 1,064-nm laser and common thermal burns. Skin lesions on Wistar
      rats were induced by a 1,064-nm CW laser at a maximum output of 40 W and by a
      copper brass bar attached to an HQ soldering iron. Histological sections of the
      lesions and the process of wound healing were evaluated. The widths of the
      epidermal necrosis and dermal denaturalization of each lesion were measured. To
      observe wound healing, the epithelial gap and wound gap were measured. Masson's
      trichrome and picrosirius red staining were also used to assess lesions and wound
      healing. The thermal damage induced by laser intensified significantly in both
      horizontal dimension and in vertical depth with increased duration of
      irradiation. Ten days after wounding, the dermal injuries induced by laser were
      more severe. Compared with the laser-induced skin damage, the skin burn induced
      by an HQ soldering iron did not show a similar development or increased in
      severity with the passage of time. The results of this study showed the pattern
      of skin damage induced by laser irradiation and a heated brass bar. This study
      also highlighted the difference between laser irradiation and thermal burn in
      terms of skin damage and wound healing, and offers insight for further treatment.

PMID- 23559276
TI  - Kinetics of apoptosis and expression of apoptosis-related proteins in rat CA3
      hippocampus cells after experimental diffuse brain injury.
AB  - The present study examined kinetics of apoptosis and expression of apoptosis
      related proteins Bcl-2, Bax, and caspase-3 in the CA3 hippocampus cells after
      diffuse brain injury (DBI) induced experimentally in rats. Percentage of
      apoptotic cells and expressions of above proteins were examined by flow cytometry
      and immunohistochemistry. Substantial neuronal apoptosis was documented in the
      CA3 hippocampus cells after DBI (22.26 +/- 2.97% at 72 h after DBI vs. 2.92 +/-
      0.88% in sham-operated animals). Expression of Bc1-2 decreased, while expression
      of Bax and caspase-3 increased after DBI, with caspase-3 expression peaking after
      that of Bax (72 vs. 48 h, respectively). Further, the Bc1-2/Bax expression ratio
      decreased prior to increase of caspase-3 expression. In conclusion, cell
      apoptosis and altered expressions of Bcl-2, Bax, and caspase-3 are present in the
      CA3 region of hippocampus after experimental DBI. Changes in the Bc1-2/Bax
      expression ratio may facilitate activation of caspase-3 and aggravate neuronal
      apoptosis after brain injury.

PMID- 23559277
TI  - Fluoxetine prevents acetylcholine-induced excitotoxicity blocking human endplate
      acetylcholine receptor.
AB  - INTRODUCTION: Fluoxetine is an open channel blocker of fetal muscle acetylcholine
      (ACh) receptor (AChR) and slow-channel mutant AChRs. It is used commonly to treat
      patients with slow-channel congenital myasthenic syndromes. Fluoxetine effects on
      adult wild-type endplate AChR are less characterized, although muscle AChR
      isoforms are differentially modulated by some drugs. METHODS: Excitotoxicity
      assays and patch clamp recordings were performed in human embryonic kidney 293
      (HEK) cells expressing wild-type or slow-channel mutant human AChRs. RESULTS:
      Fluoxetine (2-10 MUM) abolished ACh-induced death and decreased ACh-activated
      whole-cell currents in cells expressing all AChR types. In outside-out patches,
      fluoxetine rapidly curtailed ACh evoked unitary activity and macroscopic
      currents. The effect was increased if fluoxetine was applied before ACh.
      CONCLUSIONS: Fluoxetine is an open channel blocker, but it also affects AChR in
      the closed state. AChR blockade likely underlies the rescue of HEK cells from ACh
      induced death.

PMID- 23559278
TI  - Plate-based diversity subset screening: an efficient paradigm for high throughput
      screening of a large screening file.
AB  - The screening files of many large companies, including Pfizer, have grown
      considerably due to internal chemistry efforts, company mergers and acquisitions,
      external contracted synthesis, or compound purchase schemes. In order to screen
      the targets of interest in a cost-effective fashion, we devised an easy-to
      assemble, plate-based diversity subset (PBDS) that represents almost the entire
      computed chemical space of the screening file whilst comprising only a fraction
      of the plates in the collection. In order to create this file, we developed new
      design principles for the quality assessment of screening plates: the Rule of 40
      (Ro40) and a plate selection process that insured excellent coverage of both
      library chemistry and legacy chemistry space. This paper describes the rationale,
      design, construction, and performance of the PBDS, that has evolved into the
      standard paradigm for singleton (one compound per well) high-throughput screening
      in Pfizer since its introduction in 2006.

PMID- 23559279
TI  - [Human T-lymphotropic virus I/II detection in Chilean patients from Sexually
      Transmitted Diseases clinics].
AB  - BACKGROUND: The human T-lymphotropic virus I (HTLV-I) causes spastic para-paresis
      and adult T-cell leukemia/lymphoma. It can be sexually transmitted and is highly
      prevalent in Central and South America. AIM: To study HTLV-I/IIprevalence in
      serum samples obtained from two Sexually Transmitted Diseases (STD) clinics.
      MATERIAL AND METHODS: Two hundred serum samples were randomly chosen from two
      reference STD centers of Santiago. The presence of specific HTLV I/II antibodies
      was detected by indirect immunofluorescence. RESULTS: The analyzed samples came
      from participants aged 14 to 70 years. Forty nine percent were women and 76% were
      heterosexual. Only one of the 200 samples was positive (0.5%) and it came from a
      70 year-old woman, housewife, with a stable single partner, a history of
      recurrent genital ulcers, VDRL (-) and positive serology for herpes simplex
      virus. CONCLUSIONS: The prevalence of HTLV-I found in this group is similar to
      that demonstrated in other populations in Chile, except for aboriginal
      populations, and similar to international STD studies. Our data is consistent
      with the low transmissibility by sexual contact.

PMID- 23559281
TI  - [The change in the epidemiological profile of maternal mortality in Chile will
      hinder the fulfillment of the Millennium 5th goal].
AB  - BACKGROUND: The death of women during pregnancy, childbirth or puerperium,
      remains a serious public health problem worldwide. Chile is committed to comply
      with the Millennium 5th Goal of reducing maternal mortality to 9.9/100,000 live
      births in 2015. AIM: To analyze trends in maternal mortality in Chile during 2000
      2009. MATERIAL AND METHODS: A descriptive population analysis using raw data
      obtained from the yearbooks of the National Institute of Statistics of Chile.
      Maternal mortality, causes of death and age of the dead mothers were evaluated.
      The causes of maternal death were classified according to the tenth revision of
      International Classification of Diseases. Trend studies were performed using
      Pearson correlation analysis. RESULTS: In the studied period there were no
      significant changes in maternal mortality and fertility. The five major causes of
      maternal death were concurrent diseases, hypertension, abortion, obstetric
      embolism and postpartum hemorrhage. Mortality associated with concurrent illness
      showed a significant upward trend (r = 0.656, p = 0.035). Abortion associated
      mortality had a significant downward trend (r = -0.712, p = 0.023). The group of
      women 40 years and older significantly increased its birth rate (r = 0.930, p <
      0.001), this group showed the highest maternal mortality, especially in
      association with concurrent diseases. CONCLUSIONS: The increased birth rate
      occurring in women over 40 years old and its larger maternal mortality rate,
      probably will hinder the fulfillment of the Millennium 5th goal in Chile.

PMID- 23559280
TI  - [Association between adiponectin gene polymorphisms and obesity in school age
      children from Hualpen, Chile].
AB  - BACKGROUND: Several genetic polymorphisms of adiponectin have been associated to
      metabolic diseases as obesity and co-morbidities. AIM: To investigate if there
      are associations between +45TG, +276GT, -11,377CG y -11,391GA adiponectin SNPs
      (single nucleotide polymorphism) with obesity in a Chilean children population.
      MATERIAL AND METHODS: A case-control study was performed in 241 obese and 126
      normal weight children (7-11 years old) from the urban community of Hualpen,
      Biobio region. Children were classified as normal or obese, according to age and
      gender-specificpercentiles defined by Centerfor Disease Control and Prevention
      (CDC). The analysis of serum markers was carried out using commercial kits.
      Adiponectin polymorphisms were determined through a High Resolution Melting (HRM)
      enabled real time PCR and by DNA fragment sequencing. RESULTS: The observed
      allelic frequencies of the studied SNPs were over 11%. The 11,377CG polymorphism
      was associated with a high risk of obesity, calculated by the additive
      inheritance model (odds ratio = 1.389, 95% confidence interval: 1.001-1.929,p =
      0.049). CONCLUSIONS: Obese school children of the Biobio Region, have an
      increased risk of carrying the susceptibility allele polymorphism 11377CG of
      adiponectin gene.

PMID- 23559282
TI  - [Influence of nutritional status, hormones serum levels, and family history on
      breast cancer development].
AB  - BACKGROUND: Several studies have analyzed the relation between obesity and the
      hormonal imbalances generated by overweight and a family history of breast
      cancer. All of these factors are potentially implicated in the early development
      of breast cancer. AIM: To verify the existence of a significant relation between
      the nutritional status of breast cancer patients, their hormone serum levels
      (estrogens, prolactin, and progesterone), and the existence of a family history
      of breast cancer. MATERIAL AND METHODS: Retrospective data was collected from
      clinical records of 524 women diagnosed with breast cancer in a Spanish hospital.
      RESULTS: There was a positive association between estrogen, progesterone and
      prolactin serum levels and body mass index. The elevations in hormone levels
      occurred earlier in life among women with a family history of breast cancer. A
      two way ANOVA found a significant association between progesterone and prolactin
      levels with the age at diagnosis of breast cancer. CONCLUSIONS: Extreme serum
      levels of these hormones appear to be related to the early development of breast
      cancer, which in turn is influenced by the existence of a family history of
      cancer among those women with normal or average hormone levels.

PMID- 23559283
TI  - [Association of carotid intima media thickness with blood pressure and HDL
      cholesterol in children].
AB  - BACKGROUND: Cardiovascular risk factors must be controlled since childhood. AIM:
      To assess the association of carotid intima media thickness (CIMT) with the
      components of the metabolic syndrome in Children. MATERIAL AND METHODS: Cross
      sectional assessment of 299 children aged 11.5 +/- 0.9 years (58% women) with and
      without metabolic syndrome components. Anthropometric parameters and blood
      pressure were measured and a blood sample was obtained to measure blood glucose
      and lipids. CIMT was measured using high resolution ultrasound. RESULTS: Ninety
      three percent of children were post puberal, 64% were overweight and 25% had
      metabolic syndrome. Mean and maximum CIMT correlated with systolic blood pressure
      (r = 0.21 and 0.21 respectively p < 0.01). Children with a CIMT over the 75th
      percentile had higher blood pressure and lower HDL cholesterol. A stepwise
      logistic regression accepted both variables as predictors of CIMT with odds
      ratios for mean CIMT of 1.46 (1.19-1-79) and 0.81 (0.7-0.94) per five units of
      change, respectively. CONCLUSIONS: In this group of children systolic blood
      pressure and HDL cholesterol are associated to CIMT.

PMID- 23559284
TI  - [DRD4 dopamine receptor alleles in Chilean students of different ethnic origin
      and its relation with the risk for attention deficit/hyperactivity disorder].
AB  - BACKGROUND: Worldwide diversity of alleles of D4 receptor gene (DRD4), linked to
      attention deficit hyperactivity disorder (ADHD), is mostly the result of length
      and single nucleotide polymorphisms in a 48-bp tandem repeat (VNTR). Alleles
      containing from two (2R) to eleven (11R) repeats have been identified. The most
      common are 4R, 7R and 2R. AIM: To study the association of ADHD risk with DRD4
      genotypes in Chilean students. SUBJECTS AND METHODS: ADHD risk data were obtained
      through the abbreviated Conner's Scale for School Teachers in 66 Aymara children
      (11 cases and 55 controls), 91 Rapa-Nui children (60 cases ad 31 controls) and 96
      children from a mixed urban population from Santiago (51 cases and 45 controls).
      DNA extracted from saliva was amplified by polymerase chain reaction (PCR) to
      genotype the DRD4 VNTR. RESULTS: The distribution of DRD4 alleles reveals that,
      beneath the 4R allele, 7R exhibits the second highest frequencies in Aymara and
      Santiago children. In Polynesian children, 2R ranks after 4R. A statistically
      significant association between ADHD risk and 2R/4R genotype was identified in
      Polynesian children (p < 0.05; odds ratio = 3.7). CONCLUSIONS: Different DRD4
      genotypes are associated with ADHD phenotype in Chilean populations, probably as
      a consequence of their initial colonization history.

PMID- 23559285
TI  - [Effect of an acute exercise bout on Toll-like receptor 4 and inflammatory
      mechanisms in rat heart].
AB  - BACKGROUND: Toll like receptor 4 (TLR-4) is a protein located in the cell
      membrane with an important function in the immune response of the organism. Its
      activation decreases heart contractility and activates nuclear transcription
      factor kappa B (NF-kB ). This in turn, increases the synthesis of different pro
      inflammatory cytokines and the inducible enzyme nitric oxide (iNOS), which plays
      an important role in the inflammatory processes when nitric oxide production is
      enhanced. AIM: To determine if, after one session of acute exercise, expression
      of TLR-4 and iNOS, and activation of NF-kB are induced in rat cardiac tissue.
      MATERIAL AND METHODS: Exercise and control groups of eight male Wistar rats each,
      were studied. The exercise group was subjected to an acute exercise bout lasting
      one hour. After the exercise, the heart was excised to measure the expression of
      iNOS and TLR-4 genes by quantitative polyme-rase chain reaction, NF-kB activation
      by electrophoretic mobility shift assay (EMSA) and p50 by Western blot. RESULTS:
      After exercise, there was an increase in TLR-4 and of iNOS mRNA levels (+46.7 and
      +74.3% respectively). NF-kB activation and the nuclear expression of its p50
      subunit also increased significantly (+240 and +306% respectively). CONCLUSIONS:
      Increased expression of TLR4 following a session of acute exercise may contribute
      to the activation of the NF-kB signaling route, promoting the synthesis of nitric
      oxide, which could influence negatively the cardiac response to high intensity
      physical exercise.

PMID- 23559286
TI  - [Effect of sprint interval training and resistance exercise on metabolic markers
      in overweight women].
AB  - BACKGROUND: Physical activity is associated with an improvement in cardiovascular
      health, however there is a paucity of information about the effects of sprint
      interval training on individuals with high metabolic risk. AIM: To determine the
      effects of three exercise programs on anthropometric and metabolic markers in
      overweight, sedentary and prediabetic women. MATERIAL AND METHODS: Forty three
      women were ascribed to four groups matched by body mass index and body fat: high
      intensity intervals (HIT, n = 12), resistance (R, n = 8), combined group (HIT +R,
      n = 10) and control group (CG, n = 13). Participants completed 12 weeks of
      exercise intervention. Body mass index, waist circumference, percentage of fat
      mass measured by impedanciometry, blood pressure, fasting glucose, insulin and
      homeostasis model assessment for insulin resistance (HOMAlR) and fitness assessed
      using the two km walk test were measured at baseline and after the training
      period. RESULTS: No changes in anthropometric and body composition variables were
      observed. However, in HIT and R groups, significant reductions were observed on
      fasting glucose (5.4 and 16.6% respectively), insulin (18.6 and 43.4%
      respectively) and HOMA IR (24.1 and 55.4% respectively), 72 hours after the
      intervention. No significant changes were found for the observed values in the
      combined and control groups. CONCLUSIONS: HIT and resistance training improve
      glycemic control and insulin sensitivity in females with a high metabolic risk.

PMID- 23559287
TI  - [Risk assessment of critical patients requiring ambulance transfers].
AB  - BACKGROUND: Secondary transfers of critical patients between hospitals may be
      associated with risk of death and complications AIM: To determine the risk
      profile of adults subjected to secondary transfers using the Emergency Medical
      Attention System (SAMU) operating in Metropolitan Santiago. MATERIAL AND METHODS:
      Cross sectional study including 432 adults undergoing secondary transfers using
      SAMU between January 1 and June 30 2010. Demographic, biomedical, hemodynamic and
      transfer data were obtained. Cardiopulmonary arrests (CPR) and an increase in the
      Rapid Emergency Medicine Score (REMS) scale, were considered as outcome
      variables. RESULTS: CPR occurred in 6.4% of the study population and was
      significantly associated with the initial REMS score and the need for hemodynamic
      and ventilator support. The initial REMS score was a good predictor of the final
      REMS score. The final REMS was significantly associated with the presence of
      comorbidities and the need for hemodynamic and ventilator support. CONCLUSIONS:
      REMS is a useful scale to assess the risk profile of critical patients requiring
      transfers between hospitals.

PMID- 23559288
TI  - [Profile of patients with infective endocarditis admitted to a Chilean regional
      hospital].
AB  - BACKGROUND: Mortality due to infective endocarditis (IE) in Chile is close to
      30%. AIM: To report the experience with patients admitted with the diagnosis of
      IE in a regional tertiary hospital. MATERIAL AND METHODS: Retrospective study of
      107 patients aged 50 +/- 16 years (75% males) discharged with a definitive
      diagnosis of IE according to modified DUKE criteria, between years 2003 and 2010.
      Demographic variables, severity scores, clinical characteristics, bacteriology
      and hospital evolution were recorded. RESULTS: Fifty nine percent of patients had
      concomitant cardiovascular problems. APACHE II and Sequential Organ Failure
      Assessment (SOFA) scores on admission were 8.4 +/- 4.7 and 2.7 +/- 2.8
      respectively. Native valves were affected in 91% of cases (aortic and mitral
      valves in 62% and 50% of cases respectively). Prosthetic valves were affected in
      9.3% of cases. Rheumatic heart disease was the predominant primary lesion in 10%
      of patients. Antibiotics were used in 45.1% before blood cultures were performed.
      In 68% of patients blood cultures were positive. S. viridans (30.8%), S.aureus
      (18.6%) and coagulase negative Streptococci (5.6%) were the identified
      microorganisms. Intensive care unit admission was required in 48% of patients.
      Renal, heart and neurological deterioration was observed in 53, 34 and 14% of
      patients, respectively. Twenty percent of patients developed systemic embolism
      and 37% required heart surgery. Mean hospital stay was 28.3 +/- 19.1 days and 27%
      of patients died. CONCLUSIONS: In this series of patients, IE has a high
      mortality. Most patients studied were admitted in bad conditions.

PMID- 23559289
TI  - [Unilateral renal limphangiectasia: report of one case].
AB  - BACKGROUND: Renal lymphangiectasia is a rare disorder characterized by the
      presence of cystic masses in renal parenchyma, renal sinus or perinephric space.
      This condition, congenital or acquired, is probably caused by an alteration of
      renal lymphatic drainage to retroperitoneal lymph ducts. We report a 48-year-old
      woman, who consulted in the emergency room due to left flank pain and microscopic
      hematuria. Blood pressure and renal function were normal. A CT scan showed a
      multilocular cystic mass in the left renal sinus without alterations in the renal
      parenchyma. Renal lymphangiomatosis was diagnosed. The pain subsided with
      analgesics and did not recur. Annual clinical and ultrasound follow-up was
      suggested.

PMID- 23559290
TI  - [Posterior reversible encephalopathy as the first manifestation of Guillain-Barre
      syndrome. Report of one case].
AB  - BACKGROUND: We report a 56 year old male hypertensive, who presented with a
      posterior reversible encephalopathy syndrome (PRES) as an initial manifestation
      of Guillain-Barre syndrome (GBS). His first symptoms were right hemiparesis and
      hemihypoesthesia, followed by headache, dizziness, dysarthria and a general
      feeling of discomfort. On the third day, flaccid tetraparesis, impairment of
      consciousness, epileptic seizures and respiratory failure appeared, along with
      severe hypertension. Cerebral Magnetic Resonance Imaging showed the
      characteristic PRES lesions. Cerebrospinal fluid analyses revealed albumin
      cytological dissociation and nerve conduction studies showed an axonal
      demyelinating polyradiculoneuropathy, which confirmed the diagnosis of GBS.
      Treatment with intravenous immunoglobulin was given together with
      antihypertensive therapy and mechanical ventilation, achieving an important
      clinical and imaging remission of PRES, but maintaining tetraparesis during the
      hospitalization. Twelve months after discharge and regular motor rehabilitation,
      the patient achieved complete autonomy on the activities of daily living. It has
      been postulated that the autonomic failure and the elevation of circulating pro
      inflammatory cytokines in GBS may be the cause of a breach in the blood-brain
      barrier, thus causing PRES, that can completely remit with an adequate
      management.

PMID- 23559291
TI  - [Blastic plasmocytoid dendritic cell neoplasm: Report of one case].
AB  - BACKGROUND: We report a 74 years old male consulting for multiple painless non
      pruriginous pink plaques and nodules of truncal distribution that appeared 15
      days earlier. A skin biopsy disclosed a blastic plasmocytoid dendritic cell
      neoplasm. A staging CAT scan showed lymphadenopathies located around the trachea
      and its bifurcation. A bone marrow biopsy did not show tumor infiltration. The
      patient has been treated with four cycles of cyclophosphamide-doxorubicin
      vincristine-prednisone, obtaining a partial remission of the lesions.

PMID- 23559292
TI  - [Application of copper bactericidal properties in medical practice].
AB  - BACKGROUND: Copper is essential for cell metabolism in animals and plants and
      thus for life. Along centuries, copper has been identified as a metal containing
      antimicrobial properties. In recent years, laboratory assays and clinical studies
      have revealed that surfaces of metallic copper or its alloys, containing at least
      70% copper, eliminate in a few hours several pathogenic organisms including
      bacterial strains associated with nosocomial infections, influenza virus, HIV,
      and fungi such as Candida albicans. In March 2008, the American Environmental
      Protection Agency (EPA), supported by scientific evidence gathered to date,
      registered copper as the first and only metal with antimicrobial properties. We
      herein review certain mechanisms proposed for the antibacterial, antiviral and
      antifungal activity of copper. We also discuss in vitro and clinical efficacy
      studies developed world wide and in Chile, focusing on bactericidal activity of
      copper surface areas in comparison to materials typically used in hospital
      environments such as stainless steel and polymers. Scientific evidence gathered
      to date, consistently shows that the use of copper surface areas in high contact
      critical points in hospitals, significantly reduces environmental bacterial load.
      This is associated with a decreased risk of pathogen transmission to patients and
      represents therefore an interesting complement to infection control programs.

PMID- 23559293
TI  - [An update on neuropsychiatric lupus with emphasis in cognitive dysfunction].
AB  - BACKGROUND: Patients with systemic lupus erythematosus (SLE) suffer from a number
      of neuropsychiatric (NP) symptoms throughout their disease affecting them both
      physically and psychologically. We review herein the nomenclature and case
      definitions for neuropsychiatric lupus syndromes proposed by the American College
      of Rheumatology in 1999. We emphasize cognitive dysfunction and discuss
      etiological hypotheses, especially those related to the presence of antineuronal
      autoantibodies.

PMID- 23559294
TI  - [Collapsing glomerulopathy].
AB  - BACKGROUND: Collapsing glomerulopathy is a cause of nephrotic syndrome with
      massive proteinuria secondary to podocyte proliferation and glomerular collapse.
      It is characterized by an almost inevitable progression to end stage renal
      failure, poor response to treatment and high post-transplant recurrence. Its
      frequency has increased in recent years due to its common association with Human
      Immunodeficiency Virus (HIV) infection and the growing recognition of new
      etiologic agents such as drugs and parvovirus B19. Therefore, it is a disease of
      growing interest for clinicians. The aim of this review is to update the clinical
      presentation, diagnosis, pathogenesis and therapeutic alternatives of this
      disease.

PMID- 23559295
TI  - [Informed consent in the patients' rights law].
AB  - BACKGROUND: The new regulation of patients' rights creates the right to informed
      consent, which allows accepting or refusing any medical treatment. Also, the
      patient has the right to be appropriately informed about a variety of aspects
      determined by the law. Patient's autonomy has limits. Artificial acceleration of
      death, euthanasia or assisted suicide are not permitted. The problem is that the
      law does not define those situations. The law provides the intervention of Ethics
      Committees when the doctor considers that the patient exposes himself to severe
      harm or the risk of death which would be avoided. This intervention impinges on
      patient's autonomy. Patients have the right to request discharge and medical
      facilities could discharge patients against their will if they do not accept
      medical recommendations. These limitations on autonomy should be explained
      because the law apparently makes the distinction between killing, letting die and
      the Double Effect Doctrine. There is plenty of literature questioning the
      validity of both. The law fails to regulate part of the medical practice,
      regarding life and death decisions. A lack of consensus could explain this
      omission. Doctors have a right to conscientious objection to some patient's
      requests.

PMID- 23559296
TI  - [The point of view of Judaism on organ donation].
AB  - BACKGROUND: Organ transplantation frequently constitutes a source of public
      concern. Dealing with such a complex medical problems requires a process of
      recognition of the different attitudes that social groups have toward organ
      transplantation attitudes which might vary accordingly to cultural and religious
      diversity. Judaism is the focus of this review. Our objective is to contribute to
      the knowledge that Chilean health professionals have about the Jewish point of
      view on organ transplantation. The supreme value of life is a premise of Judaism,
      so saving a life should precede the enforcement of certain Old Testament's
      prohibitions. However, it is difficult and misleading to attempt to define a
      unique point of view--even though there is an overwhelming majority who are in
      favor of organ donation--because different theological interpretations and
      recommendations are continuously in debate. We conclude that the mainstream
      Jewish position is not significantly different from the contemporary Western
      thought, even though a minority in Judaism is opposed to cadaveric organ
      donation.

PMID- 23559297
TI  - [Declaration of the Chilean Academy of Medicine on atmospheric pollution in
      Santiago].

PMID- 23559298
TI  - [The Edwin Smith papyrus in the history of medicine].
AB  - BACKGROUND: The historical bases of occidental medicine precede the Hippocratic
      corpus. Between the third and first millennium B.C. Egyptian medicine developed a
      model of medical practice that was a reference horizon for other Mediterranean
      cultures. There are a great number of papyri of that time, which gathered the
      medical and surgical skills and that are matter of study. The Edwin Smith papyrus
      (PES) is one of them. We analyzed the PES in its historical context, its history,
      its structure and its medical and dental significance. Finally, we analyzed the
      relevance of PES as a sign of a change in the medicine study method in the
      ancient Egypt. PES is an insight into how medicine was practiced in ancient
      Egypt. Historically, it is also the first medical document based on objective
      observations, excluding all magical and religious perceptions, as well as the
      underlying cultural framework. The similarity between the current clinical method
      and that described in the Smith papyrus, strongly suggests the idea that part of
      the origin of medicine, can be found in ancient Egypt.

PMID- 23559299
TI  - [Research in public health: beyond international collaboration].

PMID- 23559300
TI  - [The recommended patient syndrome].

PMID- 23559301
TI  - [Modafinil, Internet and social networks: its use in health surveillance].

PMID- 23559303
TI  - [Integrating accelerated partial breast irradiation into clinical practice].

PMID- 23559304
TI  - Dentine matrix protein 1 (DMP-1) is a marker of bone-forming tumours.
AB  - Dentin matrix protein 1 (DMP-1) is highly expressed by osteocytes and is a non
      collagenous matrix protein found in dentin and bone. In this study, we determined
      the expression of DMP-1 in mature and immature human bone and examined whether
      DMP-1 is useful in distinguishing osteoid/bone-forming tumours from other primary
      and secondary bone tumours. DMP-1 expression was immunohistochemically determined
      in paraffin sections of a wide range of benign and malignant primary bone tumours
      and tumour-like lesions (n = 353). DMP-1 mRNA expression was also examined in
      osteosarcoma and fibrosarcoma cell lines as well as bone tumour specimens (n = 5)
      using real-time PCR. In lamellar and woven bone, DMP-1 was expressed in the
      matrix around osteocyte lacunae and canaliculi; osteoblasts and other cell types
      in the bone were negative. Matrix staining of the osteoid and bone was seen in
      bone-forming tumours including osteoma, osteoid osteoma, osteoblastoma and
      osteosarcoma. DMP-1 staining was also seen in fibrous dysplasia, osteofibrous
      dysplasia and chondroblastoma and in reactive bone in solitary bone cysts and
      aneurysmal bone cysts. DMP-1 was not expressed in the tumour component of other
      bone neoplasms including Ewing sarcoma, chondrosarcoma, leiomyosarcoma,
      fibrosarcoma, giant cell tumour of bone and metastatic carcinoma. DMP-1 mRNA was
      expressed in osteosarcoma cell lines and tumour samples. DMP-1 is a matrix marker
      expressed around osteocytes in human woven and lamellar bone and is useful in
      identifying osteosarcoma and other bone-forming tumours.

PMID- 23559306
TI  - Quantifying cellular dynamics by fluorescence resonance energy transfer (FRET)
      microscopy.
AB  - The cell is a spatially organized system whose function emerges from the complex
      interaction of molecular components. Such local interaction of nanometer-sized
      molecules generates patterns that span throughout the cell. Those patterns, in
      turn, regulate the molecular interactions. Understanding such simultaneous
      bidirectional causation requires quantifying the spatio-temporal progression of
      biochemical reactions in the context of a living cell. Due to its ability to
      resolve micrometer-sized structures, biological microscopy has been instrumental
      to the discovery and understanding of living systems. Functional fluorescence
      microscopy allows a cellular dynamic topographic map of proteins to be overlaid
      with topological information on the causality that determines protein state. Here
      we describe how Forster/fluorescence resonance energy transfer (FRET) can be used
      to measure the phosphorylation state of proteins in the context of the cell.

PMID- 23559305
TI  - Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count
      in pulmonary carcinoids.
AB  - Evaluation of proliferative activity is a cornerstone in the classification of
      endocrine tumors; in pulmonary carcinoids, the mitotic count delineates typical
      carcinoid (TC) from atypical carcinoid (AC). Data on the reproducibility of
      manual mitotic counting and other methods of proliferation index evaluation in
      this tumor entity are sparse. Nine experienced pulmonary pathologists evaluated
      20 carcinoid tumors for mitotic count (hematoxylin and eosin) and Ki-67 index. In
      addition, Ki-67 index was automatically evaluated with a software-based
      algorithm. Results were compared with respect to correlation coefficients (CC)
      and kappa values for clinically relevant grouping algorithms. Evaluation of
      mitotic activity resulted in a low interobserver agreement with a median CC of
      0.196 and a median kappa of 0.213 for the delineation of TC from AC. The median
      CC for hotspot (0.658) and overall (0.746) Ki-67 evaluation was considerably
      higher. However, kappa values for grouped comparisons of overall Ki-67 were only
      fair (median 0.323). The agreement of manual and automated Ki-67 evaluation was
      good (median CC 0.851, median kappa 0.805) and was further increased when more
      than one participant evaluated a given case. Ki-67 staining clearly outperforms
      mitotic count with respect to interobserver agreement in pulmonary carcinoids,
      with the latter having an unacceptable low performance status. Manual evaluation
      of Ki-67 is reliable, and consistency further increases with more than one
      evaluator per case. Although the prognostic value needs further validation, Ki-67
      might perspectively be considered a helpful diagnostic parameter to optimize the
      separation of TC from AC.

PMID- 23559307
TI  - Detection and quantification of neurotransmitters in dialysates.
AB  - Sensitive analytical methods are needed for the separation and quantification of
      neurotransmitters obtained in microdialysate studies. This unit describes methods
      that permit quantification of nanomolar concentrations of monoamines and their
      metabolites (high-performance liquid chromatography [HPLC] electrochemical
      detection), acetylcholine (HPLC-coupled to an enzyme reactor), and amino acids
      (HPLC-fluorescence detection, capillary electrophoresis with laser-induced
      fluorescence detection).

PMID- 23559308
TI  - Social fear conditioning as an animal model of social anxiety disorder.
AB  - Social fear and avoidance of social situations represent the main behavioral
      symptoms of social anxiety disorder (SAD), a disorder that is poorly elucidated
      and has rather unsatisfactory therapeutic options. Therefore, animal models are
      needed to study the underlying etiology of the disorder and possible novel
      treatment approaches. However, the current paradigms modeling SAD-like symptoms
      in rodents are not specific, as they induce numerous other behavioral deficits in
      addition to social fear and avoidance. Here, we describe the protocol for the
      social fear conditioning paradigm, an animal model of SAD that specifically
      induces social fear of unfamiliar con-specifics without potentially confounding
      alterations in other behavioral measures. Theoretical and practical
      considerations for performing the social fear conditioning paradigm in both rats
      and mice, as well as for the analysis and interpretation of the obtained data,
      are described in detail.

PMID- 23559309
TI  - The MAM rodent model of schizophrenia.
AB  - Rodent models of human disease are essential to obtain a better understanding of
      disease pathology, the mechanism of action underlying conventional treatments, as
      well as for the generation of novel therapeutic approaches. There are a number of
      rodent models of schizophrenia based on either genetic manipulations, acute or
      sub-chronic drug administration, or developmental disturbances. The prenatal
      methylazoxymethanol acetate (MAM) rodent model is a developmental disruption
      model gaining increased attention because it displays a number of histological,
      neurophysiological, and behavioral deficits analogous to those observed in
      schizophrenia patients. This unit describes the procedures required to safely
      induce the MAM phenotype in rats. In addition, we describe a simple behavioral
      procedure, amphetamine-induced hyperlocomotion, which can be utilized to verify
      the MAM phenotype.

PMID- 23559310
TI  - Suspected inguinal hernias in pregnancy--handle with care!
AB  - PURPOSE: With a newly described diagnostic pathway, we aim to avoid unnecessary
      surgical exploration for suspected symptomatic groin hernias in pregnancy.
      METHODS: A consecutive series of eighteen pregnant women was referred to our
      department due to a gradual onset of inguinal swelling and groin ache. In a
      prospective clinical study, we evaluated these patients clinically and employed
      grey-scale and colour Doppler sonography (CDS) in all cases--following a newly
      described pathway. All patients were examined pre- and post-partum by two
      qualified surgeons. Median follow-up time was 11 months. RESULTS: 4/18 of the
      suspected hernias first occurred towards the end of the first, the majority
      (12/18) in the second, 2/18 in the last trimester and all were suspected after
      clinical examination only. Most women were referred by their gynaecologists. We
      found no hernias in any of the women but always noted large varicose veins along
      the round ligament during CDS. All women gave uncomplicated birth to single
      children, one by caesarean section. Complaints subsided spontaneously within
      roughly 2 weeks after delivery. No patient developed a groin hernia until the end
      of the follow-up period. CONCLUSION: The diagnosis of an inguinal hernia with a
      first symptomatic onset during pregnancy may be wrong in most cases. Anamnesis
      and clinical examination must be backed by CDS and round ligament varicosity as
      an important differential diagnosis must always be considered. Our structured
      diagnostic pathway helps to easily make the correct diagnosis. Surgical
      exploration of the groin during pregnancy must be avoided.

PMID- 23559311
TI  - Depression-like behavior is dependent on age in male SAMP8 mice.
AB  - Aging is associated with an increased risk of depression in humans. To elucidate
      the underlying mechanisms of depression and its dependence on aging, here we
      study signs of depression in male SAMP8 mice. For this purpose, we used the
      forced swimming test (FST). The total floating time in the FST was greater in
      SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not
      observed in 12-month-old mice, when both strains are considered elderly. Of the
      two strains, only the SAMP8 animals responded to imipramine treatment. We also
      applied the dexamethasone suppression test (DST) and studied changes in the
      dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in
      the cortex, and levels of TPH2. The DST showed a significant difference between
      SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter
      density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8
      mice presented depression-like behavior that is dependent on senescence process,
      because it differs from SAMR1, senescence resistant strain.

PMID- 23559313
TI  - An Italian cohort study identifies four new pathologic mutations in the ARSA
      gene.
AB  - Metachromatic leukodystrophy is an autosomal recessive neurodegenerative disorder
      of the myelin metabolism due to the impaired function of the lysosomal enzyme
      arylsulfatase A. Three major clinical variants of metachromatic leukodystrophy
      (MLD) have been described: late infantile, juvenile, and late onset. The
      infantile form, whose clinical onset is usually before the age of 2 years, is the
      most frequent. The juvenile form manifests itself between 3 and 16 years and the
      late-onset form manifests at any time after puberty. As of today, more than 150
      mutations causing MLD have been identified in the ARSA gene that encodes
      arylsulfatase A. In this paper, we report our experience with the diagnosis of
      MLD in seven Italian patients from unrelated families. We found 11 different
      mutations, four of which have not been previously described: c.1215_1223del9
      (p.406_408del), c.601 T>C (p.Tyr201His), c.655 T>A (p.Phe219Ile), and c.87C>A
      (p.Asp29Glu). Our data show once more that there are still several mutations to
      be discovered in the ARSA gene and there are rarely repeating ones found in the
      population. The predictive value of the enzyme activity tests in regard to
      clinical manifestations is extremely limited.

PMID- 23559314
TI  - Stem cells in cerebrovascular diseases.

PMID- 23559312
TI  - Friendly drug-dealers and terrifying puppies: affective primacy can attenuate the
      N400 effect in emotional discourse contexts.
AB  - Words that are semantically congruous with their preceding discourse context are
      easier to process than words that are semantically incongruous with their
      context. This facilitation of semantic processing is reflected by an attenuation
      of the N400 event-related potential (ERP). We asked whether this was true of
      emotional words in emotional contexts where discourse congruity was conferred
      through emotional valence. ERPs were measured as 24 participants read two
      sentence scenarios with critical words that varied by emotion (pleasant,
      unpleasant, or neutral) and congruity (congruous or incongruous). Semantic
      predictability, constraint, and plausibility were comparable across the neutral
      and emotional scenarios. As expected, the N400 was smaller to neutral words that
      were semantically congruous (vs. incongruous) with their neutral discourse
      context. No such N400 congruity effect was observed on emotional words following
      emotional discourse contexts. Rather, the amplitude of the N400 was small to all
      emotional words (pleasant and unpleasant), regardless of whether their emotional
      valence was congruous with the valence of their emotional discourse context.
      However, consistent with previous studies, the emotional words produced a larger
      late positivity than did the neutral words. These data suggest that comprehenders
      bypassed deep semantic processing of valence-incongruous emotional words within
      the N400 time window, moving rapidly on to evaluate the words' motivational
      significance. 

PMID- 23559315
TI  - Cultivated limbal epithelial transplantation in children with ocular surface
      burns.
AB  - IMPORTANCE: Although several reports are available on the use of conventional and
      cultured limbal epithelium using various substrates in the treatment of limbal
      stem cell deficiency (LSCD), the patient populations studied have been largely
      adults. Thus, to our knowledge, the outcomes of this procedure exclusively in a
      pediatric population have not been reported previously. OBJECTIVE: To report the
      outcomes of autologous ex vivo cultivated limbal epithelial transplantation
      (CLET) in pediatric patients with LSCD after ocular burns. DESIGN AND SETTING: A
      retrospective, interventional case series of patients treated at the L. V. Prasad
      Eye Institute, Hyderabad, India. PARTICIPANTS: Children up to 15 years with LSCD
      secondary to chemical or thermal injury who underwent CLET from April 1, 2001,
      through June 31, 2010, with a follow-up of at least 1 year, were included in the
      study. INTERVENTION: After a limbal biopsy specimen obtained from a healthy area
      of the limbus, the limbal epithelial cells were cultured on a denuded human
      amniotic membrane substrate using a xeno-free explant culture technique. A
      monolayer of cultivated epithelial cells along with the amniotic membrane was
      transplanted on the patient's affected eye after pannus excision. In cases of
      failure, the same procedure was repeated. MAIN OUTCOMES AND MEASURES: Ocular
      surface stability and visual improvement were the primary and secondary outcome
      measures, respectively. Success was defined as a stable corneal epithelium
      without conjunctivalization. Eyes with conjunctivalization and persistent
      epithelial defects were classified as failures. RESULTS: Of the 107 eyes of 107
      patients included in this study, 73 eyes (68.2%) underwent 1 and 34 eyes (31.8%)
      underwent 2 autologous CLET procedures. At a mean follow-up of 3.4 years, 50 eyes
      (46.7%) achieved completely epithelialized, avascular, and stable ocular
      surfaces. At the final visit, 58 eyes (54.2%) had improvement in visual acuity of
      0.2 or more logMAR units. CONCLUSIONS: Autologous CLET was successful in
      restoring the ocular surface and improving vision in almost half of the children
      blinded by ocular burns.

PMID- 23559316
TI  - Concise review: erythroid versus myeloid lineage commitment: regulating the
      master regulators.
AB  - Developmental processes, like blood formation, are orchestrated by
      transcriptional networks. Those transcriptional networks are highly responsive to
      various environmental stimuli and affect common precursors resulting in increased
      production of cells of the erythroid lineage or myeloid lineage (granulocytes,
      neutrophils, and macrophages). A significant body of knowledge has accumulated
      describing transcription factors that drive differentiation of these two major
      cellular pathways, in particular the antagonistic master regulators such as GATA
      1 and PU.1. However, little is known about factors that work upstream of master
      regulators to enhance differentiation toward one lineage. These functions become
      especially important under various stress conditions like sudden loss of red
      blood cells or pathogen infection. This review describes recent studies that
      begin to provide evidence for such factors. An increased understanding of factors
      regulating cellular commitment will advance our understanding of the etiology of
      diseases like anemia, cancer, and possibly other blood related disorders.

PMID- 23559318
TI  - Acute motor axonal neuropathy and multifocal motor neuropathy: more in common
      than not.

PMID- 23559317
TI  - Preferential expansion of umbilical cord blood-derived CD34-positive cells on
      human leukemia inhibitory factor transgenic feeder cells cultured on regenerated
      silk fibroin film.
AB  - In vitro expansion of transplantable hematopoietic stem cells (HSCs) is a very
      promising approach for different clinical applications. We have recently
      developed a new culture system that facilitates in vitro expansion of
      transplantable cord blood HSCs. In our study, we constructed a recombinant
      adenovirus Ad-GFP/human leukemia inhibitory factor (hLIF) expressing hLIF. The
      hLIF gene was delivered into human embryo lung fibroblast cell line WI-38 via
      infection with Ad-GFP/hLIF. Then, the transgenic cells were cultured on
      regenerated silk fibroin (SF) films as feeder layer cells for expansion of cord
      blood CD34(+) cells. Our results showed that the hLIF transgenic WI-38 cells
      cultured on SF could express hematopoiesis-related cytokines at higher levels
      compared with control groups. The hLIF-expressing feeder layer cells cultured on
      SF in combination with cytokines more efficiently expanded CD34(+) cells and
      CD34(+) CD38(-) cells. The percentages of adhesion molecules on the expanded
      CD34(+) cells in transgenic feeder layer cells cultured on SF were higher than
      those of control groups. Interestingly, the migration rate assessed by transwell
      assay was also significantly higher than those of control groups, which suggests
      that transgenic feeder layer cells cultured on SF has powerful ability to
      maintain the homing capacity of expanded CD34(+) cells.

PMID- 23559319
TI  - [Management of synchronous colorectal liver metastases].
AB  - At time of diagnosis, 10 to 25% of patients with colorectal cancer present
      synchronous liver metastases. The treatment of such patients remains
      controversial without any evidence based organization. Therapeutic sequences are
      discussed including chemotherapy, colorectal surgery, liver resection and even
      radio-chemotherapy for some rectal cancers. In case of resectable liver
      metastases, preoperative chemotherapy offers the advantage of earlier treatment
      of micro-metastases as well as evaluation of tumor responsiveness, which can help
      shape future therapy. In this setting, different surgical strategies can be
      chosen (classical staged procedures with colorectal surgery followed by liver
      surgery, simultaneous resections or liver first approach) depending on the
      importance of the primary and metastatic tumors. The literature remains limited,
      but the results of these strategies seem identical in term of postoperative
      morbidity and long-term survival. Staged procedures are preferred in case of
      major liver resection. Location of the primary tumor on the low or mid rectum
      will necessitate preoperative long course chemoradiotherapy and a more complex
      multidisciplinary organization. For patients with extensive liver metastases, non
      resectability must be assessed by experienced surgeon and radiologist before
      treatment and during chemotherapy. In this group of patients, improved
      chemotherapy regimen associated with targeted therapies and new surgical
      strategies (portal vein embolization, ablation, staged hepatectomies...) have
      improved resection rate (15 to 30-40%) and long-term survival. Treatment
      organization for the primary tumor remains controversial. Resection of the
      primary to manage symptoms such as obstruction, perforation or bleeding is
      advocated. For patients with asymptomatic primary a non-surgical approach permits
      to begin rapidly chemotherapy and obtain a better control of the disease. On the
      other hand, initial resection of the primary may avoid complications and the need
      for urgent surgical procedures. Both of these strategies are practiced without
      definitive evidence supporting one treatment option over the other.

PMID- 23559320
TI  - Binary outputs from unitary networks.
AB  - When considering sex ratios, we have to first define the nature of the question.
      Are we referring to the gonads, secondary and accessory sex structures,
      physiology, brain, behavior, or to all of the above elements. If these elements
      are not concordant, the exceptions can prove illustrative of underlying processes
      at both the proximate and ultimate levels. At each of these levels, "sex" is the
      binary outcome resulting from the modulation of conserved networks of genes,
      proteins, cells, organs, and, in the case of the brain, discrete nuclei. These
      networks operate at multiple and sequential levels that usually are linear during
      the lifespan, but in some instances reversals are possible. For example, the
      gonads arise from a single "anlagen" and, in most instances, ovaries or testes
      result, although ovotestes are the norm in some species and gonadal reversal a
      property of other species. Other sexually dimorphic structures differentiate from
      multiple "anlaga" by reciprocal and sex-specific atrophy/hypertrophy, typically
      in an exaggerated manner, although the capacity to develop structures
      characteristic of the opposite gonadal sex remains inherent and intact. A
      perspective that integrates these different properties are presented here. 

PMID- 23559321
TI  - [Reliability and safety of intravitreal Ozurdex injections. The ZERO study].
AB  - BACKGROUND: Since July 2010 Ozurdex(r) is approved in Germany for treatment of
      macular edema from retinal vein occlusion (RVO). The objective of this
      observational study was a systemic summary and analysis of clinical experience
      regarding complications and side effects of intravitreal administration of
      dexamethasone. PATIENTS AND METHODS: In a retrospective, multicenter study
      conducted at 10 centers, 342 eyes with RVO were treated with intravitreal
      dexamethasone (Ozurdex(r), Allergan). After treatment the patients were followed
      up over a period of 8 months and intraoperative, perioperative and postoperative
      complications, such as elevated intraocular pressure and dislocation of implants
      were systematically recorded. RESULTS: No infections, endophthalmitis,
      perioperative hypotension, intraoperative lens injuries or retinal detachment
      occurred. Elevated intraocular pressure was the most common complication
      accounting for nearly 20 %. In 9 % of patients the intraocular pressure increased
      by more than 10 mmHg compared to baseline and in 6 patients to > 35 mmHg. In
      cases of known glaucoma intraocular pressure elevation was not significantly more
      frequent compared to non-glaucoma patients. In four cases a progression of lens
      opacity led to phacoemulsification and two implant dislocations in the anterior
      chamber required surgical repositioning in the vitreous cavity. In two cases a
      postinterventional macular hole was observed. CONCLUSIONS: In the clinical
      routine Ozurdex treatment has proven to be a therapy method with minimal side
      effects. In Ozurdex administration intraocular pressure elevation was observed as
      the most common side effect; however, this generally did not require surgical
      intervention. Caution is advised in patients with an anterior chamber lens and
      iridectomy. Macular holes as a rare complication might result from vitreous
      traction during the administration process. In summary, even in the clinical
      routine application of Ozurdex the complication rate was not higher than in
      registration studies.

PMID- 23559322
TI  - [Adjuvant stereotactic low energy radiation therapy of exudative age-dependent
      macular degeneration (Oraya system)].
AB  - With respect to the increasing number of patients and the risk and burden for
      patients caused by injections, a reduction in the number and frequency of
      injections with vascular endothelial growth factor (VEGF) inhibitors in exudative
      age-related macular degeneration (ARMD) is desirable. Stereotactic low-voltage x
      ray irradiation seems to be a promising approach. For this purpose the Oraya
      system is available and has shown positive results in initial studies. Pending
      presentation of phase II and III study data this adjuvant irradiation should only
      be used in clinical trials.

PMID- 23559323
TI  - [Influence of postoperative oral steroid treatment on retinal sensitivity in
      patients after macular surgery. A randomized, controlled, clinical trial].
AB  - BACKGROUND: The aim of this study was to evaluate the effect of postoperative
      systemic steroid treatment on retinal sensitivity in patients with epiretinal
      membrane (ERM) after successful surgery. PATIENTS AND METHODS: A total of 28
      patients with ERM, macular edema and visual loss were included in this study. All
      patients were treated with combined 23 gauge vitrectomy and peeling of the ERM
      and inner limiting membrane (ILM). After randomization the first group (n = 14)
      was treated with postoperative systemic steroids (100 mg prednisolone per day for
      5 days) and the second group (n = 14) served as a control group. Follow-up
      examinations were performed up to 12 months. RESULTS: After 12 months a
      statistically significant increase in visual acuity with a gain of 17/10 letters
      in the steroid/control group as well as significant decrease of the central
      retinal thickness of 107/128 um could be observed (p < 0.05). In the
      steroid/control group mean retinal sensitivity increased from 14.0/14.3 dB after
      12 months in comparison to 11.7/11.9 dB at baseline examination (p < 0.05).
      CONCLUSIONS: Postoperative oral steroid treatment does not seem to be beneficial
      in patients with macular pucker surgery.

PMID- 23559324
TI  - Liver transplantation prevents progressive neurological impairment in
      argininemia.
AB  - Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase,
      which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine
      and urea. The onset of the disease is usually in childhood, and clinical
      manifestations include progressive spastic paraparesis and mental retardation.
      Liver involvement is less frequent and usually not as severe as observed in other
      UCDs. For this reason, and because usually there is a major neurological disease
      at diagnosis, patients with argininemia are rarely considered as candidates for
      OLT despite its capacity to replace the deficient enzyme by an active one. We
      report on long-term follow-up of two patients with argininemia. Patient 1 was
      diagnosed by the age of 20 months and despite appropriate conventional treatment
      progressed to spastic paraparesis with marked limp. OLT was performed at 10 years
      of age with normalization of plasmatic arginine levels and guanidino compounds.
      Ten years post-OLT, under free diet, there is no progression of neurological
      lesions. The second patient (previously reported by our group) was diagnosed at 2
      months of age, during a neonatal cholestasis workup study. OLT was performed at
      the age of 7 years, due to liver cirrhosis with portal hypertension, in the
      absence of neurological lesions and an almost-normal brain MRI. After OLT, under
      free diet, there was normalization of plasmatic arginine levels and guanidino
      compounds. Twelve years post-OLT, she presents a normal neurological examination.
      We conclude that OLT prevents progressive neurological impairment in argininemia
      and should be considered when appropriate conventional treatment fails. 

PMID- 23559325
TI  - Differentiating hepatic abscess from malignant mimickers: value of diffusion
      weighted imaging with an emphasis on the periphery of the lesion.
AB  - PURPOSE: To evaluate the efficacy of diffusion-weighted imaging (DWI) in
      differentiating hepatic abscess from malignant mimickers with an emphasis on
      periphery of the lesions. MATERIALS AND METHODS: Thirty-nine patients with
      hepatic abscess and 74 patients with malignant hepatic tumors were included, who
      underwent gadoxetic acid-enhanced MRI. For qualitative and quantitative analysis,
      signal intensities and apparent diffusion coefficient (ADC) values of the
      periphery were assessed. Two observers reviewed DWI and ADC maps rated using a 5
      point scale. Diagnostic performance was evaluated using the receiver operating
      characteristics (ROC) curve analysis. RESULTS: The periphery of hepatic abscesses
      was T1-hypointense, arterial hyperintense, and hypointense on hepatobiliary phase
      less frequently than that of malignant tumors (P < 0.05). No hepatic abscesses
      showed peripheral washout on 3-min late phase compared with malignant tumors
      (59.5%) (P < 0.001). Both groups showed hyperintense rims on DWI, but, 37(94.9%)
      abscesses revealed rims with high ADC values compared with one (1.4%) malignant
      tumor (P < 0.001). Mean ADC values of abscesses (1.47 * 10(-3) mm(2) /s +/- 0.36
      [standard deviation]) were significantly higher than those of malignancies (0.68
      * 10(-3) mm(2) /s +/- 0.20). Diagnostic performance (area under the ROC curve
      [Az]) of DWI in identifying hepatic abscess was 0.986 and 0.982 for each
      observer. CONCLUSION: In addition to conventional MRI, DWI is helpful in
      differentiating hepatic abscess from malignant mimickers.

PMID- 23559326
TI  - FGF-2 enhances Runx-2/Smads nuclear localization in BMP-2 canonical signaling in
      osteoblasts.
AB  - Bone morphogenetic protein 2 (BMP-2) is one of the most potent regulators of
      osteoblast differentiation and bone formation. R-Smads (Smads 1/5/8) are the
      major transducers for BMPs receptors and, once activated, they are translocated
      in the nucleus regulating transcription target genes by interacting with various
      transcription factors. Runx-2 proteins have been shown to interact through their
      C-terminal segment with Smads and this interaction is required for in vivo
      osteogenesis. In particular, recruitment of Smads to intranuclear sites is Runx-2
      dependent, and Runx-2 factor may accommodate the dynamic targeting of signal
      transducer to active transcription sites. Previously, we have shown, by in vitro
      and in vivo experiments, that BMP-2 up-regulated FGF-2 which is important for the
      maximal responses of BMP-2 in bone. In this study, we found that endogenous FGF2
      is necessary for BMP-2 induced nuclear accumulation and co-localization of Runx-2
      and phospho-Smads1/5/8, while Runx/Smads nuclear accumulation and co-localization
      was reduced in Fgf2-/- osteoblasts. Based on these novel data, we conclude that
      the impaired nuclear accumulation of Runx-2 in Fgf2-/- osteoblasts reduces R
      Smads sub-nuclear targeting with a consequent decreased expression of
      differentiating markers and impaired bone formation in Fgf2 null mice.

PMID- 23559327
TI  - The limitations of models of surfactant mixing at interfaces as revealed by
      neutron scattering.
AB  - Understanding the nature of surfactant mixing at interfaces and in self-assembly
      is key to the successful and efficient exploitation of surfactant mixtures in a
      wide range of diverse applications. Phenomenological treatments often appear to
      give adequate explanations of some of the properties of straightforward mixtures,
      particularly the surface tension. However, the more detailed and direct
      information available from neutron reflectivity and small angle neutron
      scattering has identified several important situations in surfactant mixing where
      the phenomenological treatment and current theoretical models are inadequate. The
      focus of this article is to describe and discuss particular problems associated
      with such mixtures, but the issues discussed can also be considered as a paradigm
      for a wide class of mixtures.

PMID- 23559328
TI  - Pseudoduplication of the external genitalia.
AB  - A 1-year-old boy was referred to our department with a pseudoduplication of the
      external genitalia present since birth. At surgery, we performed a complete
      excision of the mass through a "Y-type" perineal incision. The boy was taken to
      our department for a regular physical examination 2 years after the surgery. The
      appearance of the perineal region was satisfactory.

PMID- 23559329
TI  - Neural conduction abnormality in the brain stem and prevalence of the abnormality
      in late preterm infants with perinatal problems.
AB  - Neurodevelopment in late preterm infants has recently attracted considerable
      interest. The prevalence of brain stem conduction abnormality remains unknown. We
      examined maximum length sequence brain stem auditory evoked response in 163
      infants, born at 33-36 weeks gestation, who had various perinatal problems.
      Compared with 49 normal term infants without problems, the late preterm infants
      showed a significant increase in III-V and I-V interpeak intervals at all 91
      910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval
      was slightly increased, without statistically significant difference from the
      controls at any click rates. These results suggest that neural conduction along
      the, mainly more central or rostral part of, auditory brain stem is abnormal in
      late preterm infants with perinatal problems. Of the 163 late preterm infant, the
      number (and percentage rate) of infants with abnormal I-V interval at 91, 227,
      455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and
      31 (18.7%). The number (and percentage rate) of infants with abnormal III-V
      interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and
      36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s
      clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed
      abnormal I-V and/or III-V intervals. CONCLUSION: Conduction in, mainly in the
      more central part, the brain stem is abnormal in late preterm infants with
      perinatal problems. The abnormality is more detectable at high- than at low-rate
      sensory stimulation. A quarter of late preterm infants with perinatal problems
      have brain stem conduction abnormality.

PMID- 23559330
TI  - The utility of FDG PET in diagnosis and follow-up of lymphoma in childhood.
AB  - Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are among the most common
      malignancies of childhood. (18)F-fluorodeoxyglucose (FDG) positron emission
      tomography (PET) can be employed for accurate staging, treatment planning, and
      response assessment in pediatric patients with lymphomas, taking advantage of the
      increased FDG uptake of the malignant cells, secondary to their increased
      metabolic needs. FDG PET has higher sensitivity than other imaging modalities to
      detect nodular or diffuse lesions and higher sensitivity than bone marrow biopsy
      to detect bone marrow infiltration. FDG PET consists of an invaluable imaging
      modality during evaluation and treatment of pediatric lymphomas.

PMID- 23559331
TI  - Medical alert tattoos in minors should not be advocated.

PMID- 23559332
TI  - Comparison between daily supplementation doses of 200 versus 400 IU of vitamin D
      in infants.
AB  - The daily supplementation of vitamin D is mandatory for infants. However, there
      are still conflicting opinions about the exact daily dose. Thus, we aimed to
      evaluate a daily supplementation dose of 200 IU is sufficient and compared the
      supplementation doses of 200 and 400 IU per day. One hundred and sixty-nine
      infants were randomly assigned to two groups (group 1, 200 IU/day; group 2, 400
      IU/day) and there were 75 infants in group 1 and 64 were in group 2 with a total
      number of 139. The median levels of 25-hydroxyvitamin D3 were significantly
      increased in group 2 at the age of 4 months (group 1, 39.60 mcg/L; group 2, 56.55
      mcg/L; p < 0.0001). We clearly demonstrated that at the age of 4 months, none of
      the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30
      mcg/L. However, 21.3% of the infants in group 1 had a level below 30 mcg/L. Thus,
      in order to avoid vitamin D deficiency and rickets, we recommend supplementation
      dose of vitamin D at 400 IU/day as a safe and effective dose.

PMID- 23559333
TI  - Monozygotic twin discordant for Down syndrome: mos 47,XX,+21/46,XX and 46,XX.
AB  - Monozygotic twins, developed from a single zygote, are almost identical in
      clinical phenotype and concordant karyotypes. Monozygotic twins with discordant
      karyotypes are thought to be quite rare. Here, we report monochorionic-diamniotic
      twins discordant for Down syndrome. On findings of prenatal ultrasonography,
      nuchal translucency thickness was different between twins, and suggested that one
      of the twins was at high risk for having chromosomal abnormalities including Down
      syndrome. The twins were monochorionic-diamniotic; therefore, chorionic villi
      sampling of the common placenta was performed. The karyotype of the chorionic
      villi cells was 46,XX, and pregnancy was maintained. After delivery, dysmorphic
      clinical features suggesting Down syndrome were found in one of the twins, while
      the other twin showed a morphologically normal appearance. Karyotypes of
      peripheral blood leukocytes were repeatedly normal in the dysmorphic twin;
      however, the karyotype of skin fibroblasts from the dysmorphic twin indicated
      Down syndrome mosaicism; 47,XX,+21[99]/46,XX[2]. The karyotype of skin
      fibroblasts from the morphologically normal twin was 46,XX. Monozygosity of the
      twins was confirmed by a short tandem repeat analysis using 16 polymorphic
      markers. A mitotic nondisjunction followed by the twinning would explain the
      discordant karyotypes between monozygotic twins. 

PMID- 23559335
TI  - Measurement uncertainty of isotopologue fractions in fluxomics determined via
      mass spectrometry.
AB  - Metabolic flux analysis implies mass isotopomer distribution analysis and
      determination of mass isotopologue fractions (IFs) of proteinogenic amino acids
      of cell cultures. In this work, for the first time, this type of analysis is
      comprehensively investigated in terms of measurement uncertainty by calculating
      and comparing budgets for different mass spectrometric techniques. The
      calculations addressed amino acids of Pichia pastoris grown on 10% uniformly
      (13)C labeled glucose. Typically, such experiments revealed an enrichment of
      (13)C by at least one order of magnitude in all proteinogenic amino acids. Liquid
      chromatography-time-of-flight mass spectrometry (LC-TOFMS), liquid chromatography
      tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC
      MS) analyses were performed. The samples were diluted to fit the linear dynamic
      range of the mass spectrometers used (10 MUM amino acid concentration). The total
      combined uncertainties of IFs as well as the major uncertainty contributions
      affecting the IFs were determined for phenylalanine, which was selected as
      exemplary model compound. A bottom-up uncertainty propagation was performed
      according to Quantifying Uncertainty in Analytical Measurement and using the
      Monte Carlo method by considering all factors leading to an IF, i.e., the process
      of measurement and the addition of (13)C-glucose. Excellent relative expanded
      uncertainties (k = 1) of 0.32, 0.75, and 0.96% were obtained for an IF value of
      0.7 by LC-MS/MS, GC-MS, and LC-TOFMS, respectively. The major source of
      uncertainty, with a relative contribution of 20-80% of the total uncertainty, was
      attributed to the signal intensity (absolute counts) uncertainty calculated
      according to Poisson counting statistics, regardless which of the mass
      spectrometry platforms was used. Uncertainty due to measurement repeatability was
      of importance in LC-MS/MS, showing a relative contribution up to 47% of the total
      uncertainty, whereas for GC-MS and LC-TOFMS the average contribution was lower
      (30 and 15%, respectively). Moreover, the IF actually present also depends on the
      isotopic purity of the carbon sources. Therefore, in the uncertainty calculation
      a carbon source purity factor was introduced and a minor contribution to the
      total uncertainty was observed. The results obtained by uncertainty calculation
      performed according to the Monte Carlo method were in agreement with the
      uncertainty value of the Kragten approach and showed a Gaussian distribution.

PMID- 23559336
TI  - Optical tweezers for medical diagnostics.
AB  - Laser trapping by optical tweezers makes possible the spectroscopic analysis of
      single cells. Use of optical tweezers in conjunction with Raman spectroscopy has
      allowed cells to be identified as either healthy or cancerous. This combined
      technique is known as laser tweezers Raman spectroscopy (LTRS), or Raman
      tweezers. The Raman spectra of cells are complex, since the technique probes
      nucleic acids, proteins, and lipids; but statistical analysis of these spectra
      makes possible differentiation of different classes of cells. In this article the
      recent development of LTRS is described along with two illustrative examples for
      potential application in cancer diagnostics. Techniques to expand the uses of
      LTRS and to improve the speed of LTRS are also suggested. 

PMID- 23559334
TI  - Salmonella modulates metabolism during growth under conditions that induce
      expression of virulence genes.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative
      pathogen that uses complex mechanisms to invade and proliferate within mammalian
      host cells. To investigate possible contributions of metabolic processes to
      virulence in S. Typhimurium grown under conditions known to induce expression of
      virulence genes, we used a metabolomics-driven systems biology approach coupled
      with genome-scale modeling. First, we identified distinct metabolite profiles
      associated with bacteria grown in either rich or virulence-inducing media and
      report the most comprehensive coverage of the S. Typhimurium metabolome to date.
      Second, we applied an omics-informed genome-scale modeling analysis of the
      functional consequences of adaptive alterations in S. Typhimurium metabolism
      during growth under our conditions. Modeling efforts highlighted a decreased
      cellular capability to both produce and utilize intracellular amino acids during
      stationary phase culture in virulence conditions, despite significant abundance
      increases for these molecules as observed by our metabolomics measurements.
      Furthermore, analyses of omics data in the context of the metabolic model
      indicated rewiring of the metabolic network to support pathways associated with
      virulence. For example, cellular concentrations of polyamines were perturbed, as
      well as the predicted capacity for secretion and uptake.

PMID- 23559337
TI  - Analysis of nucleosides and nucleotides in infant formula by liquid
      chromatography-tandem mass spectrometry.
AB  - A method for the simultaneous analysis of nucleosides and nucleotides in infant
      formula using reversed-phase liquid chromatography-tandem mass spectrometry is
      described. This approach is advantageous for compliance testing of infant formula
      over other LC-MS methods in which only nucleotides or nucleosides are measured.
      Following sample dissolution, protein was removed by centrifugal ultrafiltration.
      Chromatographic analyses were performed using a C18 stationary phase and gradient
      elution of an ammonium acetate/bicarbonate buffer, mass spectrometric detection
      and quantitation by a stable isotope-labelled internal standard technique. A
      single laboratory validation was performed, with spike recoveries of 80.1-112.9%
      and repeatability relative standard deviations of 1.9-7.2%. Accuracy as bias was
      demonstrated against reference values for NIST1849a certified reference material.
      The method has been validated for the analysis of bovine milk-based, soy-based,
      caprine milk-based and hydrolysed milk protein-based infant formulae.

PMID- 23559338
TI  - Graphene-assisted room-temperature synthesis of 2D nanostructured hybrid
      electrode materials: dramatic acceleration of the formation rate of 2D metal
      oxide nanoplates induced by reduced graphene oxide nanosheets.
AB  - A new prompt room temperature synthetic route to 2D nanostructured metal oxide
      graphene-hybrid electrode materials can be developed by the application of
      colloidal reduced graphene oxide (RGO) nanosheets as an efficient reaction
      accelerator for the synthesis of delta-MnO2 2D nanoplates. Whereas the synthesis
      of the 2D nanostructured delta-MnO2 at room temperature requires treating
      divalent manganese compounds with persulfate ions for at least 24 h, the addition
      of RGO nanosheet causes a dramatic shortening of synthesis time to 1 h,
      underscoring its effectiveness for the promotion of the formation of 2D
      nanostructured metal oxide. To the best of our knowledge, this is the first
      example of the accelerated synthesis of 2D nanostructured hybrid material induced
      by the RGO nanosheets. The observed acceleration of nanoplate formation upon the
      addition of RGO nanosheets is attributable to the enhancement of the oxidizing
      power of persulfate ions, the increase of the solubility of precursor MnCO3, and
      the promoted crystal growth of delta-MnO2 2D nanoplates. The resulting
      hybridization between RGO nanosheets and delta-MnO2 nanoplates is quite powerful
      not only in increasing the surface area of manganese oxide nanoplate but also in
      enhancing its electrochemical activity. Of prime importance is that the present
      delta-MnO2 -RGO nanocomposites show much superior electrode performance over most
      of 2D nanostructured manganate systems including a similar porous assembly of RGO
      and layered MnO2 nanosheets. This result underscores that the present RGO
      assisted solution-based synthesis can provide a prompt and scalable method to
      produce nanostructured hybrid electrode materials.

PMID- 23559339
TI  - The effects of the WT1 gene on apoptosis and development-related gene expression
      in porcine kidney fibroblasts and swine testis cells.
AB  - The Wilm's tumor 1 gene (WT1) encodes zinc finger proteins that function as tumor
      suppressors, and play important roles in the development of the genito-urinary
      system and other organs. Its precise function in the development of porcine
      tissues and organs, which is an attractive transplantation resource for certain
      human diseases, is still unclear. Here, we sought to define the role of WT1 in
      porcine kidney and testis tissues using porcine kidney fibroblasts (PKFs) and
      swine testis (ST) cells as in vitro models, both of which express WT1. The
      recombinant plasmids pLV3-WT1 shRNA and pIRES2 -WT1-EGFP were constructed to
      respectively down- and up-regulate the WT1 gene in porcine cells. The role of WT1
      in cell proliferation was investigated by RT-PCR, immunocytochemical staining,
      apoptosis analysis, and Western blot. The pLV3-WT1 shRNA dramatically reduced WT1
      expression at both the transcription and protein levels. The down-regulation of
      WT1 directly led to early cell apoptosis, and changes in Sf1, Sox9, and Gdnf gene
      expression in PKFs and ST cells. In contrast, up-regulation of WT1 gave no
      obvious phenotype in ST cells. Our results demonstrate that WT1 is essential for
      the survival of PKFs and ST cells because it regulates apoptosis- and development
      related genes in the cells; however, no obvious effect was observed when WT1 was
      over-expressed.

PMID- 23559340
TI  - Genome-wide survey and expression analysis of the MADS-box gene family in
      soybean.
AB  - MADS-box genes encode important transcription factors in plants that are involved
      in many processes during plant growth and development. An investigation of the
      soybean genome revealed 106 putative MADS-box genes. These genes were classified
      into two classes, type I and type II, based on phylogenetic analysis. The soybean
      type II group has 72 members, which is higher than that of Arabidopsis,
      indicating that soybean type II genes have undergone a higher rate of duplication
      and/or a lower rate of gene loss after duplication. Soybean MADS-box genes are
      present on all chromosomes. Like Arabidopsis and rice MADS-box genes, soybean
      MADS-box genes expanded through tandem gene duplication and segmental duplication
      events. There are many duplicate genes distributed across the soybean genome,
      with two genomic regions, i.e., MADS-box gene hotspots, where MADS-box genes with
      high degrees of similarity are clustered. Analysis of high-throughput sequencing
      data from soybean at different developmental stages and in different tissues
      revealed that MADS-box genes are expressed in embryos of various stages and in
      floral buds. This expression pattern suggests that soybean MADS-box genes play an
      important role in soybean growth and floral development.

PMID- 23559341
TI  - Spatial distribution of trachoma cases in the City of Bauru, State of Sao Paulo,
      Brazil, detected in 2006: defining key areas for improvement of health resources.
AB  - INTRODUCTION: The objective of this study was to analyze the spatial behavior of
      the occurrence of trachoma cases detected in the City of Bauru, State of Sao
      Paulo, Brazil, in 2006 in order to use the information collected to set priority
      areas for optimization of health resources. METHODS: the trachoma cases
      identified in 2006 were georeferenced. The data evaluated were: schools where the
      trachoma cases studied, data from the 2000 Census, census tract, type of housing,
      water supply conditions, distribution of income and levels of education of
      household heads. In the Google Earth(r) software and TerraView(r) were made
      descriptive spatial analysis and estimates of the Kernel. Each area was studied
      by interpolation of the density surfaces exposing events to facilitate to
      recognize the clusters. RESULTS: Of the 66 cases detected, only one (1.5%) was
      not a resident of the city's outskirts. A positive association was detected of
      trachoma cases and the percentage of heads of household with income below three
      minimum wages and schooling under eight years of education. CONCLUSIONS: The
      recognition of the spatial distribution of trachoma cases coincided with the
      areas of greatest social inequality in Bauru city. The micro-areas identified are
      those that should be prioritized in the rationalization of health resources.
      There is the possibility of using the trachoma cases detected as an indicator of
      performance of micro priority health programs.

PMID- 23559342
TI  - Involvement and interactions of different immune cells and their cytokines in
      human visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) or kala-azar, a disseminated infection of the
      lymphoreticular system of the body, is marked by severe defect in immune system
      of the host. Successful cure of VL depends on the immune status of the host in
      combination with the effects of the antileishmanial drugs. The rationale approach
      towards eradication of this disease would be to potentiate the immune functioning
      of the host in addition to parasite killing. This review deals with different
      aspects of adaptive and innate immune responses and explores their role in
      protection or pathogenesis of VL. IL-10 has emerged as the principal cytokine
      responsible for disease pathogenesis, although evidences regarding its source
      during active VL remain inconclusive. On the other hand, IFNgamma,under the
      influence of IL-12, is mostly correlated with healing of the disease. Chemokines
      are important in mounting cell-mediated immune response as they can prevent
      parasite invasion in association with cytokines. Different types of T cells like
      CD4, CD8 and NK T cells also contribute to the immunology of this disease. In
      spite of conflicting reports, the role of regulatory T cells in VL pathogenesis
      is important. Recently discovered Th17 subset and its different members have been
      reported to perform diverse functions in the course of VL and leishmaniasis as a
      whole. Innate immune responses, depending on the cell types, are essential in
      early parasite detection and subsequent development of an efficient NK cell
      response. Immunotherapy targeting IL-10 could be looked upon as an interesting
      option for the treatment of VL.

PMID- 23559343
TI  - In vitro detection of hepatitis C virus in platelets from uninfected individuals
      exposed to the virus.
AB  - INTRODUCTION: Despite hepatocytes being the target cells of hepatitis C virus
      (HCV), viral ribonucleic acid RNA has been detected in other cells, including
      platelets, which have been described as carriers of the virus in the circulation
      of infected patients. Platelets do not express cluster differentiation 81 CD81,
      the main receptor for the virus in hepatocytes, although this receptor protein
      has been found in megakaryocytes. Still, it is not clear if HCV interacts with
      platelets directly or if this interaction is a consequence of its association
      with megakaryocytes. The aim of this study was to evaluate the interaction of HCV
      with platelets from non-infected individuals, after in vitro exposure to the
      virus. METHODS: Platelets obtained from 50 blood donors not infected by HCV were
      incubated in vitro at 37 degrees C for 48h with serum containing 100,000IU/mL of
      genotype 1 HCV. After incubation, RNA extracted from the platelets was assayed
      for the presence of HCV by reverse transcription - polymerase chain reaction RT
      PCR. RESULTS: After incubation in the presence of virus, all samples of platelets
      showed HCV RNA. CONCLUSIONS: The results demonstrate that, in vitro, the virus
      interacts with platelets despite the absence of the receptor CD81, suggesting
      that other molecules could be involved in this association.

PMID- 23559344
TI  - Approaches towards tick and tick-borne diseases control.
AB  - Ticks are obligate haematophagous ectoparasites of wild and domestic animals as
      well as humans, considered to be second worldwide to mosquitoes as vectors of
      human diseases. Tick-borne diseases are responsible worldwide for great economic
      losses in terms of mortality and morbidity of livestock animals. This review
      concerns to the different tick and tick-parasites control methods having a major
      focus on vaccines. Control of tick infestations has been mainly based on the use
      of acaricides, a control measure with serious drawbacks, as responsible for the
      contamination of milk and meat products, as a selective factor for acaricide
      resistant ticks and as an environmental contaminant. Research on alternatives to
      the use of acaricides is strongly represented by tick vaccines considered a more
      cost-effective and environmentally safe strategy. Vaccines based on the Bm86 tick
      antigen were used in the fi rst commercially available cattle tick vaccines and
      showed good results in reducing tick numbers, affecting weight and reproductive
      performance of female ticks which resulted in reduction of cattle tick
      populations over time and consequently lower reduction of the pathogen agents
      they carry.

PMID- 23559345
TI  - Prevalence and risk factors for Toxoplasma gondii infection among pregnant and
      postpartum women attended at public healthcare facilities in the City of Niteroi,
      State of Rio de Janeiro, Brazil.
AB  - INTRODUCTION: To determine the prevalence of immunoglobulin G (IgG) and
      immunoglobulin M (IgM) anti-Toxoplasma gondii antibodies among pregnant and
      postpartum women attended within the public healthcare system in Niteroi, State
      of Rio de Janeiro,and to detect possible exposure factors associated with T.
      gondii infection in this population. METHODS: IgM and IgG anti- T. gondii
      antibodies were investigated in 276 pregnant and 124 postpartum women by using
      the indirect immunofluorescence (IFAT) and immunoenzymatic assay (ELISA)
      techniques. The participants were selected by convenience sampling. All these 400
      patients filled out a free and informed consent statement, answered an
      epidemiological questionnaire and were informed about the disease. RESULTS: Among
      the 400 samples analyzed, 234 (58.5%) were reactive to IgG anti-T. gondii
      antibodies, according to the IFAT and/or ELISA assay. One pregnant woman was
      found to be reactive to IgM anti- T. gondii antibodies, with an intermediate IgG
      avidity test. Risk factor analysis showed that seropositivity was significantly
      associated (p<0.05) with age, contact with cats and presence of rodents at home.
      Through a logistic regression model, these associations were confirmed for age
      and contact with cats, while education at least of the high school level was
      found to be a protective factor. CONCLUSIONS: The prevalence rate of IgG anti-T.
      gondii antibodies in the city of Niteroi was high and the risk factors for
      infection detected after multivariate analysis were: age over 30 years, contact
      with cats and education levels lower than university graduate level.

PMID- 23559346
TI  - Use of fillers as adjunct therapy for the treatment of lower face hemifacial
      spasm.
AB  - The treatment of hemifacial spasm with periorbital injections of higher doses of
      botulinum toxin can create disfiguring and undesirable weakness in the lower face
      during active facial movements. The use of asymmetric hyaluronidate filler
      injections to the lower face provides a refinement allowing for a lowered
      neurotoxin dose. The filler creates a ballasting effect and involuntary facial
      movement. The conventional filler effect also further reduces asymmetric
      nasolabial folds and marionette lines. Fifteen of 18 patients with lower facial
      spasms found the filler toxin combination an improvement over neurotoxin alone.

PMID- 23559347
TI  - Cloning of the Xuhuai goat PPARgamma gene and the preparation of transgenic
      sheep.
AB  - This study aimed to clone the peroxisome proliferator-activated receptor gamma
      (PPARgamma) gene of the Xuhuai goat and to make transgenic sheep using
      intratesticular injection, so as to improve the meat quality and flavor by
      increasing the intramuscular fat content. The coding sequence of the goat
      PPARgamma gene was 1,428 bp, encoding 475 amino acids. Its similarity with other
      species was 81 (chicken), 89 (mouse), 92 (pig), 98 (cow), and 99% (sheep). The
      similarity of the corresponding amino acid sequences was 92.9, 97.3, 98.3, 99.6,
      and 99.8%, respectively. The signal peptide region of the PPARgamma protein was
      not found in this study, demonstrating that the protein is not secreted. RT-PCR
      and western blot revealed that PPARgamma was expressed in vitro, and the protein
      was localized in the cytoplasm. The PPARgamma gene was expressed in F1 transgenic
      sheep at both the mRNA and the protein levels; the positive ratio was 13.7%.

PMID- 23559348
TI  - State-level cancer treatment costs: how much and who pays?
AB  - BACKGROUND: Cancer treatment accounts for approximately 5% of national health
      expenditures. However, no state-level estimates of cancer treatment costs have
      been published. METHODS: In analyses of data from the Medical Expenditure Panel
      Survey, the National Nursing Home Survey, the U.S. Census Bureau, the Current
      Population Survey, and the Centers for Medicare & Medicaid Services, this study
      used regression modeling to estimate annual state-level cancer care costs during
      2004 to 2008 for 4 categories of payers: all payers, Medicare, Medicaid, and
      private insurance. RESULTS: State-level cancer care costs ranged from $227
      million to $13.6 billion (median = $2.0 billion) in 2010 dollars. Medicare paid
      between 25.1% and 36.1% of these costs (median = 32.5%); private insurance paid
      between 36.0% and 49.6% (median = 43.3%); and Medicaid paid between 2.0% and 8.8%
      (median = 4.8%). Cancer treatment accounted for 3.8% to 8.7% of all state-level
      medical expenditures (median = 7.0%), 8.5% to 15.0% of state-level Medicare
      expenditures (median = 10.6%), 1.0% to 4.9% of state-level Medicaid expenditures
      (median = 2.2%), and 5.5% to 10.9% of state-level private insurance expenditures
      (median = 8.7%). CONCLUSIONS: The costs of cancer treatment were substantial in
      all states and accounted for a sizable fraction of medical expenditures for all
      payers. The high cost of cancer treatment underscores the importance of
      preventing and controlling cancer as one approach to manage state-level medical
      costs.

PMID- 23559349
TI  - Acute pulmonary vasoreactivity test with sildenafil or nitric monoxide before
      left ventricular assist device implantation.
AB  - There has been no established medical therapy to ameliorate pulmonary
      hypertension (PH) owing to left heart disease (LHD-PH). It has recently been
      shown that the left ventricular assist device (LVAD) can improve LHD-PH and
      therefore has the potential to become a major bridge tool for heart
      transplantation (HTx). However, some patients still have persistent PH even after
      LVAD treatment. It is essential to demonstrate the reversibility of end-organ
      dysfunction, including PH, prior to implantable LVAD treatment, especially in
      Japan, because implantable LVAD treatment is indicated only as bridge to
      transplantation. Here we report a patient with LHD-PH whose PH was demonstrated
      to be reversible by the acute pulmonary vasoreactivity test (APVT) with nitrogen
      monoxide (NO) and the phosphodiesterase-5 inhibitor sildenafil. Both inhaled NO
      and sildenafil reduced pulmonary vascular resistance, but pulmonary capillary
      wedge pressure was increased by NO, which was conversely decreased under
      increased cardiac output by sildenafil. After the patient was listed as an HTx
      recipient, pulmonary vascular resistance recovered down to an acceptable range
      with LVAD treatment. Based on these findings, we suggest that the APVT with
      sildenafil may be a useful and safe tool to predict improvement of PH after LVAD
      treatment. 

PMID- 23559351
TI  - Non HPV-related cervical squamous cell carcinoma with unusual histologic
      characteristics mimicking a giant immature condyloma: a case report.

PMID- 23559350
TI  - Strong expression of the neuronal transcription factor FOXP2 is linked to an
      increased risk of early PSA recurrence in ERG fusion-negative cancers.
AB  - BACKGROUND AND AIMS: Transcription factors of the forkhead box P (FOXP1-4) family
      have been implicated in various human cancer types before. The relevance and role
      of neuronal transcription factor FOXP2 in prostate cancer is unknown. METHODS: A
      tissue microarray containing samples from more than 11 000 prostate cancers from
      radical prostatectomy specimens with clinical follow-up data was analysed for
      FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre
      existing ERG fusion (by fluorescence in situ hybridisation and
      immunohistochemistry) and cell proliferation (Ki67 labelling index) data.
      RESULTS: There was a moderate to strong FOXP2 protein expression in basal and
      secretory cells of normal prostatic glands. As compared with normal cells, FOXP2
      expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was
      linked to advanced tumour stage, high Gleason score, presence of lymph node
      metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative,
      but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high
      Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status.
      CONCLUSIONS: These data demonstrate that similar high FOXP2 protein levels as in
      normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion
      type' prostate cancer. It may be speculated that interaction of FOXP2 with
      members of pathways that are specifically activated in 'non fusion-type' cancers
      may be responsible for this phenomenon.

PMID- 23559353
TI  - Mitochondrial myopathy with autophagic vacuoles in patients with the m.8344A>G
      mutation.
AB  - BACKGROUND AND AIMS: In mitochondrial myopathy, autophagy is presumed to play an
      important role in mitochondrial dysfunction. Rimmed vacuoles (RVs), a sign of
      autophagy, can be seen as a secondary phenomenon in muscle ragged-red fibres
      (RRFs), whereas the uncommon presentation is that some fibres contain RVs, but
      without any mitochondrial abnormalities. To investigate the pathogenesis beneath
      this pathological phenomenon. METHODS: We reviewed 783 skeletal muscle specimens
      and selected five obtained from patients with suspected mitochondrial myopathy,
      characterised by clearly visible autophagic vacuoles in non-RRFs, besides the
      coexistence of RRFs and cytochrome oxidase-negative fibres. Immunohistochemical
      staining with LC-3, and electron microscopy studies were performed. Using
      resequencing microarray and a next-generation sequencing system, the
      mitochondrial DNA was screened for mutations and the heteroplasmic level was
      measured in skeletal muscle and blood. RESULTS: Muscle fibres with RVs and RRFs,
      as well as some morphologically normal fibres, stained strongly for LC-3.
      Electron microscopy disclosed significant abnormal mitochondrial proliferation
      and existence of autophagic vacuoles. After mutation screening, m.8344A>G in the
      tRNA(Lys) gene was detected in two patients. The heteroplasmy of mutated G was
      45.1% in skeletal muscle and 17.8% in blood in patient 1; patient 2 exhibited
      80.3% mutated G in skeletal muscle and 25.2% in blood. CONCLUSIONS: These
      findings demonstrate a new pathological phenotype for the m.8344A>G mutation-
      related disease and also provide pathological evidence of a correlation between
      mitochondrial abnormalities and autophagy.

PMID- 23559352
TI  - Mast cells in infantile haemangioma possess a primitive myeloid phenotype.
AB  - AIMS: Recent reports on infantile haemangioma (IH) have demonstrated a primitive
      population of interstitial cells expressing the embryonic transcription factor,
      Nanog, with decreasing abundance during involution. In this report we
      investigated the expression of Nanog on mast cells in all three phases of IH
      progression. METHODS: Paraffin-embedded sections of six proliferating, six
      involuting and six involuted IH lesions were used to investigate the expression
      of tryptase, Nanog, CD45, CD34 and GLUT-1 by immunostaining. RESULTS: Mast cells,
      identified by their expression of tryptase, were located in the interstitium of
      IH lesions. 93%, 42% and 0% of these tryptase(+) cells also expressed Nanog, in
      proliferating, involuting and involuted IH, respectively. CONCLUSIONS: The
      identification of an abundant population of tryptase(+)/Nanog(+) cells in IH is
      novel. The relative loss of Nanog expression as IH involutes may be a result of
      maturation and/or proliferation of these cells. This report supports the
      primitive nature of IH.

PMID- 23559354
TI  - Clinicopathological significance of CADM4 expression in invasive ductal carcinoma
      of the breast.
AB  - AIMS: Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor involved in
      cell adhesion. Loss or decreased expression of CADM4 has been associated with the
      development and progression of some cancers. The purpose of this study was to
      investigate the clinicopathological significance of CADM4 expression in breast
      cancer. METHODS: We constructed tissue microarrays to evaluate the
      immunohistochemical expression of CADM4 in 256 cases of invasive ductal carcinoma
      (IDC) and 45 cases of ductal carcinoma in situ (DCIS). RESULTS: CADM4 was
      expressed in 37 (82.2%) DCIS cases, and in 173 (67.6%) IDC cases. CADM4
      expression was higher in DCIS than in IDC (p=0.049). Loss or decrease of CADM4
      expression was significantly correlated with higher histological grade (p=0.020),
      absence of oestrogen receptors (p<0.001), absence of progesterone receptors
      (p=0.024), and overexpression of c-erbB-2 (p=0.018). In univariable and
      multivariable Cox regression analyses of all 256 IDC cases, CADM4 expression was
      not significantly associated with overall and disease-free survival. However, it
      showed a significant positive association with longer disease-free survival in
      187 stages I and II IDC cases (p=0.039, log-rank test). CONCLUSIONS: Loss or
      decrease of CADM4 expression seems to play an important role in breast cancer
      invasiveness, and it is associated with poorer biological parameters. CADM4 can
      be used as a novel marker predicting risk of recurrence and disease outcomes in
      stages I and II IDC.

PMID- 23559355
TI  - Clinical trial outcomes of high- and extra high-profile breast implants.
AB  - BACKGROUND: Clinical data concerning potential risks and benefits associated with
      the use of high- and extra high-profile breast implants are lacking. OBJECTIVES:
      The authors assess the risk of adverse events (AE) with high- and extra high
      profile breast implants compared with low- to moderate-profile breast implants in
      patients enrolled in long-term clinical studies. METHODS: Relative risks (RR) of
      capsular contracture (CC), moderate to severe malposition, and secondary
      procedure were calculated using Cox proportional hazards regression, adjusting
      for patient, procedure, and device characteristics among patients enrolled in the
      primary augmentation cohorts of the Core (NCT00689871; round, silicone-filled
      implants) and 410 (NCT00690339; shaped, highly cohesive silicone-filled implants)
      clinical studies. Study pooling provided comparisons of implant shape and fill,
      as well as contributed to relative outcome. Analyses were also stratified by
      preoperative breast measures. RESULTS: In the Core study (N = 454; 907 implants;
      mean follow-up 7.2 years; 3669 person-years), and the combined Core and 410
      studies (N = 4412; 8811 implants; mean follow-up 3.0 years; 14 528 person-years),
      risk of CC, secondary procedures, and mastopexy as a secondary procedure were
      reduced in high-profile versus low- to moderate-profile breast implants (P <
      .05). The risk of moderate to severe malposition was not significantly different
      between high-profile and low- to moderate-profile breast implants in the Core or
      combined studies (RR, 0.58 [95% confidence interval (CI), 0.22-1.51] and RR, 0.72
      [95% CI, 0.31-1.70], respectively). Analyses stratified by preoperative breast
      measures did not indicate higher risk of CC, malposition, or secondary procedure
      among patients with either smaller (<17 cm) or larger (>=17 cm) preoperative
      measures. CONCLUSIONS: Among primary augmentation patients with round, silicone
      filled, or shaped, highly cohesive silicone-filled implants, high- and extra high
      profile implants were associated with lower risks of CC, secondary procedures,
      and mastopexy and were not associated with greater risks of moderate to severe
      malposition versus low- to moderate-profile implants. LEVEL OF EVIDENCE: 3.

PMID- 23559356
TI  - Calcite crystal growth by a solid-state transformation of stabilized amorphous
      calcium carbonate nanospheres in a hydrogel.

PMID- 23559357
TI  - A 1-year prospective survey of candidemia in Italy and changing epidemiology over
      one decade.
AB  - PURPOSE: The aim of this study was to assess the epidemiology of candidemia and
      antifungal susceptibility profiles of Candida isolates in Italy through a
      prospective surveillance study and to evaluate changes compared to a previous
      survey performed in one Italian region (Lombardy) in 1997-1999. METHODS: A
      prospective laboratory-based surveillance of candidemia was performed in Italy
      from January to December 2009. For each case a questionnaire was filled in, and
      the first isolate was collected and tested for in vitro antifungal
      susceptibility. RESULTS: During our 12-month survey, 467 episodes of candidemia
      were reported from 34 centres (30 located in Lombardy) and 464 isolates
      collected. Candida albicans was the predominant species (overall incidence 50.4
      %), but the proportion varied considerably from 52.1 % in Lombardy hospitals to
      45.2 % hospitals located outside this region. The second most frequent species
      was C. glabrata in Lombardy and C. parapsilosis in other regions. Comparison of
      the 1997-1999 and 2009 data on episodes of candidemia in Lombardy revealed a
      threefold increase in incidence (from 0.38 to 1.19 per 1,000 admissions), aging
      of infected patients, decline in crude mortality (from 35 to 27.1 %) and an
      increased proportion of C. glabrata etiology (from 12.8 to 20.3 %).
      Susceptibility testing confirmed the broad activity of amphotericin B and
      echinocandins. Decreased susceptibility to fluconazole was found in 24.9 % of the
      tested isolates. CONCLUSIONS: The results of this latest survey confirm the high
      rate of candidemia in Italy and show changes in some of the epidemiological
      tracts, such as aging of infected patients, increased proportion of C. glabrata
      infections, increased diagnosis in medical wards, and improvement in patients'
      survival.

PMID- 23559358
TI  - Tularemia during pregnancy.
AB  - Tularemia is a zoonotic infection caused by Francisella tularensis with a
      worldwide distribution and diverse clinical manifestations. Although F.
      tularensis has been recognized as a human pathogen for a century, there are few
      reports regarding the occurrence of tularemia in pregnant women and its effect on
      the fetus; only seven cases have been reported in the literature. In view of the
      sparse literature, it is not clear whether tularemia increases the risk of
      adverse pregnancy outcomes. In this paper we review tularemia infection during
      pregnancy, its complications and management. In addition, we present a case of
      tularemia that occurred in the first trimester of pregnancy and resulted in third
      trimester intrauterine fetal death, highlighting the consequences of tularemia in
      pregnancy and the importance of early detection and treatment. 

PMID- 23559360
TI  - [Percutaneous ablation of metastases: where are we and new techniques].
AB  - When a metastatic disease is localized and slowly evolving either spontaneously
      or after a general treatment, a local treatment may be proposed. For about 15
      years, image-guided percutaneous ablation has been developed which allows to
      treat tumors with temperature modifications. These mini-invasive techniques may
      be repeated in patients whose disease may be chronic. Ablation techniques are
      also used in a more palliative manner on bone metastases to obtain pain relief.

PMID- 23559359
TI  - Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese
      patients with chronic heart failure: results of the randomized, controlled,
      double-blind, Multistep Administration of bisoprolol IN Chronic Heart Failure II
      (MAIN-CHF II) study.
AB  - Bisoprolol fumarate (bisoprolol) is a beta-blocker widely used to treat chronic
      heart failure (CHF). However, few studies have compared its efficacy and safety
      with those of the widely used beta-blocker carvedilol in Japanese patients with
      CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control
      drug; however, the trial was discontinued after an off-label use of bisoprolol
      was approved during the study. Bisoprolol and carvedilol were administered for 32
      weeks in 31 and 28 patients, respectively. The mean maintenance doses of
      bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean
      durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate
      changes were similar in both groups. The mean changes from baseline to Week 32 in
      left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups;
      11.7 % +/- 8.6 % vs 10.1 % +/- 10.5 %), LV end-diastolic volume (-37.5 +/- 48.7
      vs -24.7 +/- 29.4 ml), and LV end-systolic volume (-41.9 +/- 43.0 vs -29.3 +/-
      25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups.
      The cumulative event-free rate for a composite of cardiovascular death or
      admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the
      bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of
      patients were titrated up to the maintenance doses of bisoprolol and carvedilol,
      respectively. Bisoprolol, at half the dose used in other countries, is well
      tolerated and is as effective as carvedilol for treating Japanese patients with
      mild to moderate CHF. 

PMID- 23559361
TI  - Autologous fibrin membrane combined with solid platelet-rich plasma in the
      management of perforated corneal ulcers: a pilot study.
AB  - IMPORTANCE: The combined use of autologous fibrin membrane and the eye platelet
      rich plasma (E-PRP) clot could be considered as a new surgical alternative for
      the closure of corneal perforations. OBJECTIVE: To evaluate the use of autologous
      solid platelet-rich plasma in combination with an autologous fibrin membrane as a
      surgical alternative for wound closure in perforated corneal ulcers. DESIGN: Both
      the fibrin membrane and the E-PRP clot were prepared with the patient's own blood
      just before the operation. Nylon stitches were used to fixate the fibrin membrane
      to the conjunctiva and then the E-PRP clot was placed over the corneal
      perforation, underneath the fibrin membrane. A temporal partial tarsorrhaphy was
      performed at the end of the procedure. We conducted postoperative monitoring for
      3 months. SETTING Vissum Corporacion Oftalmologica, Alicante, Spain.
      PARTICIPANTS: Eleven patients with perforated corneal ulcers. INTERVENTION:
      Surgical alternative for the closure of corneal perforation. MAIN OUTCOMES AND
      MEASURES: Corneal biomicroscopy, fluorescein test, digital tonometry. RESULTS: In
      all cases the corneal perforation was sealed. The fibrin membrane was present
      over the corneal surface for the first 3 to 5 days and then gradually
      disappeared. No evidence of infection or inflammation was detected. Digital
      tonometry confirmed acceptable levels of ocular tonus in all cases from day 2
      after the operation. No patients reported pain, discomfort, or other symptoms,
      and no complications were observed. After 3 months' follow-up, there was no
      evidence of relapses or perforations. Corneal grafting was eventually performed
      in 7 of the 11 cases. CONCLUSIONS AND RELEVANCE: The combined use of autologous
      fibrin membrane and E-PRP clot is a safe and effective surgical alternative for
      the closure of corneal perforations. This technique can be considered as a
      temporary measure until the condition of the cornea permits definite
      intervention.

PMID- 23559362
TI  - Comparative stability of the bioresorbable ferric crosslinked hyaluronic acid
      adhesion prevention solutions.
AB  - The Intergel(r) ferric crosslinked hyaluronate (FeHA) adhesion prevention
      solution (APS) (FDA) is associated with serious post-operative complications
      (Henley, http://www.lawyersandsettlements.com/features/gynecare-intergel/intergel
      timeline.html, 2007; FDA, 2003; Roman et al., Fertil Steril 2005, 83 Suppl 1:1113
      1118; Tang et al., Ann Surg 2006;243(4):449-455; Wiseman, Fertil Steril
      2006;86(3):771; Wiseman, Fertil Steril 2006;85(4):e7). This prompted us to
      examine the in situ stability of crosslinked HA materials to hyaluronidase lyase
      degradation. Variables such as ferric ionic crosslink density, HA concentration,
      gel geometry, and molecular weight (MW) of HA polymer were studied. Various
      formulations of the crosslinked "in house" [Isayeva et al., J Biomed Mater Res:
      Part B - Appl Biomater 2010, 95B (1):9-18] FeHA (0.5%, w/v; 30, 50, 90%
      crosslinked), the Intergel(r) FeHA (0.5%, w/v; 90%), and the non-crosslinked HA
      (0.05-0.5%, w/v) were degraded at a fixed activity of hyaluronidase lyase from
      Streptomyces hyalurolyticus (Hyase) at 37 degrees C over time according to the
      method [Payan et al., J Chrom B: Biomed Sci Appl 1991;566(1):9-18]. Under our
      conditions, the data show that the crosslink density affects degradation the
      most, followed by HA concentration and then gel geometry. We found that MW has no
      effect. Our results are one possible explanation of the observations that the
      Intergel(r) FeHA APS (0.5%, w/v; 90%) material persisted an order of magnitude
      longer than expected [t1/2 = 500 hrs vs. t1/2 = 50 hrs (FDA; Johns et al., Fertil
      Steril 1997;68(1):37-42)]. These data also demonstrate the sensitivity of the in
      vitro hyaluronidase assay to predict the in situ stability of crosslinked HA
      medical products as previously reported [Sall et al., Polym Degrad Stabil
      2007;92(5):915-919].

PMID- 23559363
TI  - Small GTPase Rap1 regulates cell migration through regulation of small GTPase
      RhoA activity in response to transforming growth factor-beta1.
AB  - Transforming growth factor (TGF)-beta1 regulates diverse cellular functions.
      Particularly, TGF-beta1 induces monocyte migration to sites of injury or
      inflammation in early period, whereas TGF-beta1 inhibits cell migration in late
      phase. In this study, we attempted to understand how TGF-beta1 suppresses cell
      migration in late phase. We found that TGF-beta1 of short exposure induces the
      production of chemokines, such as macrophage inflammatory protein (MIP)-1alpha,
      by Raw 264.7 cells. However, knock-down of small GTPase RhoA by sh-RhoA inhibited
      the production of MIP-1alpha and macrophage migration, suggesting that RhoA is
      essential for expression of this chemokine. An activator of Epac (exchange
      proteins directly activated by cAMP; a guanine nucleotide exchange factor of
      Rap1), 8CPT-2Me-cAMP which leads to Rap1 activation abrogated MIP-1alpha
      expression and macrophage migration. Indeed, GTP-RhoA and GTP-Rap1 levels were
      reciprocally regulated in a time-dependent manner following TGF-beta1
      stimulation. 8CPT-2Me-cAMP suppressed GTP-RhoA levels, whereas si-Rap1 augmented
      GTP-RhoA levels and cell migration. TGF-beta1 produced cAMP in late period and si
      RNAs of Epac1 and Epac2 reduced GTP-Rap1 levels leading to promotion of GTP-RhoA
      levels. Furthermore, si-RNA of ARAP3 (Rap-dependent RhoGAP) increased GTP-RhoA
      level and cell migration. Therefore, we propose the mechanism that prolonged TGF
      beta1 treatment produce cAMP, which activates sequentially Epac, Rap1 and ARAP3,
      resulting in suppression of RhoA, chemokine expression, and macrophage migration.
      Contrary to the general concept that Rap1 stimulates cell migration, we
      demonstrated in this study that Rap1 inhibits cell migration by suppression of
      RhoA activity in response to TGF-beta1.

PMID- 23559364
TI  - Partial sternotomy coronary surgery with triple-vessel disease in dextrocardia
      and situs inversus totalis.
AB  - Dextrocardia associated with situs inversus totalis is a rare congenital
      condition. A small number of cases with these conditions have been reported who
      underwent myocardial revascularization via the on-pump or off-pump techniques.
      Among them, only 1 patient with dextrocardia and situs inversus totalis was
      reported to have the procedure performed with minimally invasive coronary surgery
      via a right anterior small thoracotomy. However, the case was a single-vessel
      disease and only one graft was achieved. We describe the case of a 65-year old
      female patient with triple-vessel obstructive coronary diseases who was
      successfully revascularized with three grafts using a minimally invasive
      technique. This was achieved via partial sternotomy and employing off-pump
      coronary artery bypass grafting.

PMID- 23559365
TI  - Chemical interactions of mercury species and some transition and noble metals
      towards metallothionein (Zn7MT-2) evaluated using SEC/ICP-MS, RP-HPLC/ESI-MS and
      MALDI-TOF-MS.
AB  - The chemical affinities of three submetallomes ("Mn, Co, Ni, Cu, Cd"; "Pd, Pt,
      Au"; and "Hg, CH3Hg, C2H5Hg-THI") towards metallothionein-2 (Zn7MT-2) in a
      physiological solution environment were evaluated using SEC/ICP-MS together with
      RP-HPLC/ESI-IT-MS and MALDI-TOF-MS, and followed the order: "Zn(2+) < Cu(2+),
      Cd(2+) > Ni(2+) > Mn(2+), Co(2+)"; "Pd(2+) > Au(3+) > Pt(2+)"; and "Hg(2+) >
      CH3Hg(+) > C2H5Hg-THI". Besides these, the structural change and composition of
      the CH3Hg-MT-2 complexes formed during the CH3Hg(+) titration process were
      further investigated using CD spectroscopy, RP-HPLC/ESI-MS and MALDI-TOF-MS,
      indicating that linear and more hydrophobic (CH3Hg)xMT-2 (x = 12, 13, 14, 15, 16,
      17, 18, 19 and 20) were formed. This information is important in understanding
      the interactions of the metals with Zn7MT-2 and their corresponding biological
      functions and toxicities. 

PMID- 23559366
TI  - Advance information modulates the global effect even without instruction on where
      to look.
AB  - When observers are asked to make an eye movement to a visual target in the
      presence of a near distractor, their eyes tend to land on a position in between
      the target and the distractor, an effect known as the global effect. While it was
      initially believed that the global effect is a mandatory eye movement strategy,
      recent studies have shown that explicit instructions to make an eye movement to a
      certain part of the scene can overrule the effect. We here investigate whether
      such top-down influences are also found when people are not actively involved in
      an explicit eye movement task, but instead, make eye movements in the service of
      another task. Participants were presented with arrays of yellow and green discs,
      each containing a letter, and were asked to identify a target letter. Because the
      discs were presented away from fixation, participants made an eye movement to the
      array of discs on most of the trials. An analysis of the landing sites of these
      eye movements revealed that, even without an explicit instruction, observers take
      the advance information about the colour of the disc containing the target into
      account before moving their eyes. Moreover, when asking participants to maintain
      fixation for intervals of different durations, it was found that the implicit top
      down influences operated on a very similar time-scale as previously observed for
      explicit eye movement instructions.

PMID- 23559367
TI  - No effect of the estrogen receptor alpha gene polymorphisms in the etiology of
      precocious puberty in girls.
AB  - Estrogen plays a crucial role in the development and function in reproductive
      physiology. Estrogens regulate cellular activity through binding to estrogen
      receptor alpha (ERalpha) and beta (ERbeta). ERalpha polymorphisms have been
      associated with changes in age at menarche, menopause onset, and fertility. The
      aim of this study is to investigate the relationship of ERalpha gene
      polymorphisms with central precocious puberty (CPP) in girls. Two hundred and one
      (201) Korean girls with idiopathic CPP were included in this study along with 100
      healthy Korean female adults with pubertal maturation within normal age who
      served controls. Auxological and endocrine parameters were measured, and both
      patients and controls were genotyped for PvuII (397 T->C) and XbaI (351 A->G)
      polymorphisms in the ERalpha gene. A significantly lower incidence of the CC
      genotype with PvuII polymorphism were noted among CPP girls than controls (11.9%
      vs. 22%, P=0.021). However, the clinical parameters did not differ among the 3
      genotypes. In addition, there was no significant difference in patients with the
      XbaI polymorphism compared to controls. The present study reveals that neither
      PvuII nor XbaI polymorphisms in the ERalpha gene are associated with onset and
      progression of puberty. However, further studies are needed to validate the exact
      function of these polymorphisms.

PMID- 23559368
TI  - Paeoniflorin, a monoterpene glycoside, attenuates lipopolysaccharide-induced
      neuronal injury and brain microglial inflammatory response.
AB  - Chronic activation of microglial cells endangers neuronal survival through the
      release of various proinflammatory and neurotoxic factors. Paeoniflorin (PF), a
      water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall,
      has a wide range of pharmacological functions, such as anti-oxidant, anti
      inflammatory, and anti-cancer effects. Neuroprotective potential of PF has also
      been demonstrated in animal models of neuropathologies. Here, we have examined
      the efficacy of PF in the repression of inflammation-induced neurotoxicity and
      microglial inflammatory response. In organotypic hippocampal slice cultures, PF
      significantly blocked lipopolysaccharide (LPS)-induced hippocampal cell death and
      productions of nitric oxide (NO) and interleukin (IL)-1beta. PF also inhibited
      the LPS-stimulated productions of NO, tumor necrosis factor-alpha, and IL-1beta
      from primary microglial cells. These results suggest that PF possesses
      neuroprotective activity by reducing the production of proinflammatory factors
      from activated microglial cells.

PMID- 23559369
TI  - Isolated oral histoplasmosis presenting as Fever of unknown origin in a
      Portuguese hemodialysis patient.
AB  - The authors report a clinical case of an isolated oral histoplasmosis in a
      hemodialysis patient that presented with fever of unknown origin and had an
      unremarkable physical examination. During the investigation, a Gallium scan
      showed uptake in the oral cavity and soon after the oral cavity examination
      revealed a granulomatous lesion on the tooth 26. Histopathologic findings were
      compatible with histoplasmosis. The treatment regimen included liposomal
      amphotericin B followed by itraconazole consolidation therapy, and side effects
      did not occur. Both clinical evolution and outcome were favorable. Oral
      histoplasmosis in a non-immunosuppressed patient is extremely rare.

PMID- 23559370
TI  - The nature of the U=C double bond: pushing the stability of high-oxidation-state
      uranium carbenes to the limit.
AB  - Treatment of [K(BIPM(Mes)H)] (BIPM(Mes)={C(PPh2NMes)2}(2-); Mes=C6H2-2,4,6-Me3)
      with [UCl4(thf)3] (1 equiv) afforded [U(BIPM(Mes)H)(Cl)3(thf)] (1), which
      generated [U(BIPM(Mes))(Cl)2(thf)2] (2), following treatment with benzyl
      potassium. Attempts to oxidise 2 resulted in intractable mixtures, ligand
      scrambling to give [U(BIPM(Mes))2] or the formation of
      [U(BIPM(Mes)H)(O)2(Cl)(thf)] (3). The complex [U(BIPM(Dipp))(MU
      Cl)4(Li)2(OEt2)(tmeda)] (4) (BIPM(Dipp)={C(PPh2NDipp)2}(2-); Dipp=C6H3-2,6-iPr2;
      tmeda=N,N,N',N'-tetramethylethylenediamine) was prepared from
      [Li2(BIPM(Dipp))(tmeda)] and [UCl4(thf)3] and, following reflux in toluene, could
      be isolated as [U(BIPM(Dipp))(Cl)2(thf)2] (5). Treatment of 4 with iodine (0.5
      equiv) afforded [U(BIPM(Dipp))(Cl)2(MU-Cl)2(Li)(thf)2] (6). Complex 6 resists
      oxidation, and treating 4 or 5 with N-oxides gives [{U(BIPM(Dipp)H)(O)2- (MU
      Cl)2Li(tmeda)] (7) and [{U(BIPM(Dipp)H)(O)2(MU-Cl)}2] (8). Treatment of 4 with
      tBuOLi (3 equiv) and I2 (1 equiv) gives [U(BIPM(Dipp))(OtBu)3(I)] (9), which
      represents an exceptionally rare example of a crystallographically authenticated
      uranium(VI)-carbon sigma bond. Although 9 appears sterically saturated, it
      decomposes over time to give [U(BIPM(Dipp))(OtBu)3]. Complex 4 reacts with
      PhCOtBu and Ph2CO to form [U(BIPM(Dipp))(MU-Cl)4(Li)2(tmeda)(OCPhtBu)] (10) and
      [U(BIPM(Dipp))(Cl)(MU-Cl)2(Li)(tmeda)(OCPh2)] (11). In contrast, complex 5 does
      not react with PhCOtBu and Ph2CO, which we attribute to steric blocking. However,
      complexes 5 and 6 react with PhCHO to afford (DippNPPh2)2C=C(H)Ph (12). Complex 9
      does not react with PhCOtBu, Ph2CO or PhCHO; this is attributed to steric
      blocking. Theoretical calculations have enabled a qualitative bracketing of the
      extent of covalency in early-metal carbenes as a function of metal, oxidation
      state and the number of phosphanyl substituents, revealing modest covalent
      contributions to U=C double bonds.

PMID- 23559371
TI  - Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate
      steroid receptor coactivator 3 protein turnover.
AB  - The p160 steroid receptor coactivators (SRCs) SRC-1, SRC-2 [nuclear receptor
      coactivator (NCOA)2], and SRC-3 [amplified in breast cancer 1 (AIB1)/NCOA3] are
      key pleiotropic "master regulators" of transcription factor activity necessary
      for cancer cell proliferation, survival, metabolism, and metastasis. SRC
      overexpression and overactivation occur in numerous human cancers and are
      associated with poor clinical outcomes and resistance to therapy. In prostate
      cancer (PC), the p160 SRCs play critical roles in androgen receptor
      transcriptional activity, cell proliferation, and resistance to androgen
      deprivation therapy. We recently demonstrated that the E3 ubiquitin ligase
      adaptor speckle-type poxvirus and zinc finger (POZ) domain protein (SPOP)
      interacts directly with SRC-3 and promotes its cullin 3-dependent ubiquitination
      and proteolysis in breast cancer, thus functioning as a potential tumor
      suppressor. Interestingly, somatic heterozygous missense mutations in the SPOP
      substrate-binding cleft recently were identified in up to 15% of human PCs
      (making SPOP the gene most commonly affected by nonsynonymous point mutations in
      PC), but their contribution to PC pathophysiology remains unknown. We now report
      that PC-associated SPOP mutants cannot interact with SRC-3 protein or promote its
      ubiquitination and degradation. Our data suggest that wild-type SPOP plays a
      critical tumor suppressor role in PC cells, promoting the turnover of SRC-3
      protein and suppressing androgen receptor transcriptional activity. This tumor
      suppressor effect is abrogated by the PC-associated SPOP mutations. These studies
      provide a possible explanation for the role of SPOP mutations in PC, and
      highlight the potential of SRC-3 as a therapeutic target in PC.

PMID- 23559372
TI  - Paracrine Wnt signaling both promotes and inhibits human breast tumor growth.
AB  - Wnt signaling in mouse mammary development and tumorigenesis has been heavily
      studied and characterized, but its role in human breast cancer remains elusive.
      Although Wnt inhibitors are in early clinical development, it is unclear whether
      they will be of therapeutic benefit to breast cancer patients, and subsequently,
      to which ones. To address this, we generated a panel of Wnt reporting human
      breast cancer cell lines and identified a previously unrecognized enrichment for
      the ability to respond to Wnt in the basal B or claudin-low subtype, which has a
      poor prognosis and no available targeted therapies. By co-injecting Wnt3A
      expressing human mammary fibroblasts with human breast cancer cell lines into
      mouse mammary fat pads, we showed that elevated paracrine Wnt signaling was
      correlated with accelerated tumor growth. Using this heterotypic system and a
      dual lentiviral reporter system that enables simultaneous real-time measurement
      of both Wnt-responsive cells and bulk tumor cells, we analyzed the outcome of
      elevated Wnt signaling in patient-derived xenograft (PDX) models. Interestingly,
      the PDX models exhibited responses not observed in the cell lines analyzed.
      Exogenous WNT3A promoted tumor growth in one human epidermal growth factor
      receptor 2-overexpressing PDX line but inhibited growth in a second PDX line
      obtained from a patient with triple-negative breast cancer. Tumor suppression was
      associated with squamous differentiation in the latter. Thus, our work suggests
      that paracrine Wnt signaling can either fuel or repress the growth of human
      breast cancers depending on yet to be determined aspects of the molecular
      pathways they express.

PMID- 23559373
TI  - CD4+ cell-dependent granuloma formation in humanized mice infected with
      mycobacteria.
AB  - We have used humanized mice, in which human immune cells differentiate de novo
      from transplanted cord blood progenitor cells, to study the human immune
      responses to infection with Mycobacterium bovis bacillus Calmette-Guerin and
      Mycobacterium tuberculosis. Granulomas with a core containing giant cells, human
      CD68(+) macrophages, and high bacilli numbers surrounded by a layer of CD3(+) T
      cells and a fibrotic response encapsulating the lesions were observed in livers
      and lungs from bacillus Calmette-Guerin-infected humanized mice but not in
      nonhumanized infected controls. Paradoxically, humanized mice contained higher
      mycobacterial numbers in organs than nonhumanized controls. The enhancement of
      bacterial load was mediated by human CD4(+) cells and associated to an increased
      expression of Programmed Death-1 protein and CD57 on T cells, molecules
      associated with inhibition and senescence. The lesions from mice depleted of
      CD4(+) cells were scarcer, minimal, and irregular compared with those from mice
      depleted of CD8(+) cells or nondepleted controls. Granulomas of bacillus Calmette
      Guerin-infected humanized mice administered with a TNF-neutralizing TNF receptor
      fusion molecule preserved their structure, but contained higher levels of
      intracellular bacilli. Extended necrosis was observed in granulomas from M.
      tuberculosis- but not bacillus Calmette-Guerin-infected humanized mice. Our data
      indicate that humanized mice can be used as a model to study the formation and
      maintenance of human granuloma in tuberculosis and other infectious or
      noninfectious diseases.

PMID- 23559374
TI  - Defining pyromes and global syndromes of fire regimes.
AB  - Fire is a ubiquitous component of the Earth system that is poorly understood. To
      date, a global-scale understanding of fire is largely limited to the annual
      extent of burning as detected by satellites. This is problematic because fire is
      multidimensional, and focus on a single metric belies its complexity and
      importance within the Earth system. To address this, we identified five key
      characteristics of fire regimes--size, frequency, intensity, season, and extent-
      and combined new and existing global datasets to represent each. We assessed how
      these global fire regime characteristics are related to patterns of climate,
      vegetation (biomes), and human activity. Cross-correlations demonstrate that only
      certain combinations of fire characteristics are possible, reflecting fundamental
      constraints in the types of fire regimes that can exist. A Bayesian clustering
      algorithm identified five global syndromes of fire regimes, or pyromes. Four
      pyromes represent distinctions between crown, litter, and grass-fueled fires, and
      the relationship of these to biomes and climate are not deterministic. Pyromes
      were partially discriminated on the basis of available moisture and rainfall
      seasonality. Human impacts also affected pyromes and are globally apparent as the
      driver of a fifth and unique pyrome that represents human-engineered
      modifications to fire characteristics. Differing biomes and climates may be
      represented within the same pyrome, implying that pathways of change in future
      fire regimes in response to changes in climate and human activity may be
      difficult to predict.

PMID- 23559375
TI  - Classical subjective expected utility.
AB  - We consider decision makers who know that payoff-relevant observations are
      generated by a process that belongs to a given class M, as postulated in Wald
      [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate
      this Waldean piece of objective information within an otherwise subjective
      setting a la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New
      York)] and show that this leads to a two-stage subjective expected utility model
      that accounts for both state and model uncertainty.

PMID- 23559376
TI  - Gene expression analysis of bovine oocytes with high developmental competence
      obtained from FSH-stimulated animals.
AB  - Recent progress in the ovarian stimulation protocol used for bovine in vitro
      maturation and fertilization, especially through optimization of the follicle
      stimulating hormone (FSH) withdrawal period ("coasting") after ovarian pre
      treatment with FSH, has significantly improved blastocyst outcome. Despite this
      important success, the underlying factors leading to improved oocyte quality have
      not yet been identified. The aim of this project was to compare the transcriptome
      of germinal vesicle-stage oocytes collected from FSH-stimulated cows after
      various coasting periods (20, 44, 68, and 92 hr) to determine which transcripts
      were accumulated or depleted during the rise and fall of competence. Oocytes from
      each coasting period were compared to the three other times (optimal conditions,
      44 and 68 hr; under-matured, 20 hr; and over-matured, 92 hr) per animal, allowing
      each cow to be its own control (24 collections). Microarray analysis revealed
      that between 5 and 338 transcripts were significantly different across the six
      comparisons, with an important longitudinal modulation in terms of gene
      expression profile. Not surprisingly, as the transcriptional activity decreased
      in these oocytes, several transcripts that are significantly modulated during
      coasting are related to RNA processing functions, as shown by functional
      analysis. Ingenuity Pathway Analysis also highlighted another important function:
      the control of chromosome segregation. The results presented here indicate that
      the quality gained with the optimal coasting time does not last, and also
      suggests a possible mechanism of control by transcript degradation that could be
      implicated if the oocyte is not ovulated at the right time.

PMID- 23559377
TI  - Partial protective of chickens against Eimeria tenella challenge with recombinant
      EtMIC-1 antigen.
AB  - Eimeria tenella microneme protein 1 (EtMIC-1) is highly conserved with TgMIC-2,
      which is involved in parasite binding specifically to host cells. Little is known
      about the immune responses and protective efficacy against E. tenella infection
      with EtMIC-1 antigen. In the present study, the recombinant proteins of E.
      tenella mature MIC-1 and adhesive domain (von Willebrand factor type A domain,
      EtMIC-1-VD) were obtained, protective efficacy against E.tenella infection and
      the mucosal immune response, which is induced in broilers was evaluated. The
      antibody levels and the transcription profiles of cytokine of chickens, such as
      interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), were detected after
      being immunized three times with the recombinant EtMIC-1 and EtMIC-1-VD by ELISA
      assay and quantitative real-time PCR, respectively. The results showed that both
      groups of chickens, after being immunized with 100 MUg EtMIC-1 or EtMIC-1-VD
      antigen, induced about tenfold higher IgG levels compared to the nonimmune
      groups. The transcription profiles of IL-12 and IFN-gamma of the immunized groups
      were significantly higher than the control groups as well. The anticoccidial
      index of the group immunized with 100 MUg EtMIC-1 and the group immunized with
      100 MUg EtMIC-1-VD were 167.2 and 165.5, respectively, which are significantly
      higher than low-dose immunized groups and challenged control groups. Our data
      suggests that VD domain is the key functional structure of EtMIC-1 that could
      trigger a significant humoral and cellular response against E. tenella infection,
      and EtMIC-1 had the potential in imparting partial protection in chickens against
      homologous challenge.

PMID- 23559378
TI  - Comparative therapeutic effect of probiotic Lactobacillus casei alone and in
      conjunction with antiprotozoal drugs in murine giardiasis.
AB  - Various antiprotozoal drugs have been used to counteract the spread of
      giardiasis. However, due to increase in resistance to these compounds, there is
      an urgent need to find a natural biocompatible product to fight the pathogen in
      more healthy and effective way. The present study was designed to compare the
      therapeutic effect of probiotic Lactobacillus casei alone and in conjunction with
      antiprotozoal drugs on the outcome of giardiasis in murine model. BALB/c mice
      were challenged with Giardia intestinalis trophozoites, and 1 day after
      infection, these mice were treated with either probiotic alone or in conjunction
      with antiprotozoal drugs. Cyst, trophozoite, and lactobacilli counts were
      monitored vis-a-vis histopathological alterations in the small intestine. It was
      found that albendazole administered orally 1 day after Giardia infection was the
      most effective antiprotozoal drug among albendazole, tinidazole, metronidazole,
      and nitazoxanide. It reduced both the severity and duration of giardiasis. More
      specifically, oral administration of the probiotic L. casei in conjunction with
      albendazole further reduced the Giardia infection as was evident by the restored
      normal gut morphology. This suggests that probiotics and antiprotozoal drugs in
      combination may be the better alternative therapy for treatment of
      gastrointestinal diseases and enhanced recovery.

PMID- 23559379
TI  - Antiprotozoal screening of traditional medicinal plants: evaluation of crude
      extract of Psoralea corylifolia against Ichthyophthirius multifiliis in goldfish.
AB  - Ichthyophthirius multifiliis (also called "ich") is an external protozoan
      parasite that may infest almost all freshwater fish species and caused
      significant economic damage to the aquaculture industry. Since the use of
      malachite green was banned, there have been relatively few effective alternative
      strategies for controlling I. multifiliis infections. The present study was
      designed to screen potential antiparasitic medicinal plants based on our previous
      studies, and comprehensively evaluate in vitro and in vivo anti-ich activity of
      selected plant extracts. The screening results showed that the methanol extract
      of Psoralea corylifolia had the highest activity against I. multifiliis theronts.
      In vivo theront trials demonstrated that 1.25 mg/L or more concentrations of P.
      corylifolia methanol extract caused 100 % mortality during the 4-h exposure
      period, and the subsequent in vitro trials indicated that the minimum
      concentration of P. corylifolia methanol extract that prevented the initial
      infestation was 2.50 mg/L. Protomonts and encysted tomonts surviving trials
      suggested that encysted tomonts were less susceptible to P. corylifolia methanol
      extract than protomonts, and the methanol extract of P. corylifolia at a
      concentration of 5.00 mg/L could kill 100 % of protomonts and 88.89 % of encysted
      tomonts. It was also observed that after 12-h exposure of protomonts or encysted
      tomonts to 2.50 mg/L of P. corylifolia methanol extract, the theronts emerged
      from encysted tomonts led to more infection level than the ones in the other
      groups. The results suggested that whether the protomonts finish encystment is
      crucial to the survival, reproduction, and theronts infectivity. In addition, our
      results showed that long duration (24 h) and high concentration (5.00 mg/L)
      significantly reduced the survival and reproduction of I. multifiliis tomont
      exited from the fish after in-bath treatment, and it is indicated that P.
      corylifolia methanol extract had a potential detrimental effect on I. multifiliis
      trophont in situ.

PMID- 23559380
TI  - Larvicidal activity of lipophilic extract of Hypericum carinatum (Clusiaceae)
      against Aedes aegypti (Diptera: Culicidae) and benzophenones determination.
AB  - In this study, the larvicidal activity of an enriched fraction of the major
      lipophilic phenolic compounds from Hypericum carinatum Griseb. (Clusiaceae) was
      investigated against larvae of Aedes aegypti (Diptera: Culicidae), the main
      vector of dengue virus in Brazil. The larval mortality rate ranged 37.33 to 72.00
      % at concentrations of 66-200 MUg/mL. The effect demonstrated to be dose
      dependent. The lethal concentration 50 % and confidence interval were 100 and 88
      111 MUg/mL, respectively. The results could be attributed to the presence of
      cariphenone A and cariphenone B in concentrations of 1.24 +/- 0.04 and 0.56 +/-
      0.01 %, respectively, determined by high-performance liquid chromatography.
      Besides, the results reinforce the potential of genus Hypericum as source of
      alternative insecticides.

PMID- 23559381
TI  - Three-dimensional dixon fat-water separated rapid breathheld imaging of
      myocardial infarction.
AB  - PURPOSE: To develop a breathhold three-dimensional (3D) Dixon technique for fat
      suppressed imaging of myocardial infarction. MATERIALS AND METHODS: A pulse
      sequence was developed that uses a radial fan-beam k-space segmentation scheme
      for efficient coverage of k-space, enabling 3D scans in a single breathhold. The
      sequence uses a dual-echo bipolar readout to enable Dixon fat-water separation
      for improved visualization of epicardial and pericardial delayed enhancement. The
      3D Dixon method was compared with a conventional 2D fast gradient recalled echo
      (FGRE) -based technique in 25 patients. RESULTS: Pericardial visualization scores
      and confidence were higher while overall image quality and artifacts were
      slightly worse for 3D Dixon compared with 2D FGRE. Robust fat suppression was
      achieved in 21 of 25 cases using the 3D Dixon method. CONCLUSION: A 3D breathhold
      method for fat-water separated imaging of myocardial delayed enhancement was
      developed and validated.

PMID- 23559382
TI  - Retracted: A proteomic approach for investigation of photosynthetic apparatus in
      plants.

PMID- 23559386
TI  - Single-molecule detection of 5-hydroxymethylcytosine in DNA through chemical
      modification and nanopore analysis.

PMID- 23559387
TI  - Regional migratory osteoporosis and transient osteoporosis of the hip: are they
      all the same?
AB  - We hypothesized that regional migratory osteoporosis (RMO) and transient
      osteoporosis of the hip (TOH) terms describe a common disease process. Therefore,
      based on our patient, we aimed to review the pathogenesis, diagnosis, and
      treatment of both diseases. The patient was a pregnant woman in her third
      trimester with sacral insufficiency fracture, which was shortly followed by
      migratory arthralgia of both hips and ankles in a proximal to distal direction.
      She was operated (core decompression) for both hips and ankles, and she was
      symptom free at 17th month. RMO and TOH have an unclear etiology, share the
      similar course, and bear a self-limiting nature. Both disorders may be the same
      clinical entity with a common pathogenesis. Probably, many of RMO patients were
      labeled as TOH, and therefore, RMO has been underrepresented. In conclusion, we
      think that both RMO and TOH describe a common disease process. Either the
      diagnosis is RMO or TOH, the management will be the same. Finally, the
      conservative treatment protocol is a better treatment modality and must be obeyed
      even in resistant cases.

PMID- 23559388
TI  - Adalimumab-associated antiphospholipid syndrome: a case report and review of the
      literature.
AB  - This study aims for the presentation of the first reported case of adalimumab
      associated antiphospholipid syndrome (APS) and review of the literature on
      adalimumab-induced vasculitis and APS. A case of APS associated with adalimumab
      use in a 67-year-old woman is reported. The English medical literature was
      reviewed for antitumor necrosis factor (TNF) agents and their association with
      APS and vasculitis. Adalimumab is a fully humanized monoclonal antibody targeted
      against TNF alpha that is widely used in the treatment of rheumatoid arthritis,
      juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis,
      psoriasis, and Crohn's disease. Literature review reveals several cases of anti
      TNF-induced vasculitis including cases associated with adalimumab. We report the
      first case of adalimumab-induced APS in a 67-year-old woman who developed APS and
      vasculitis associated with de novo positive anti-cardiolipin (aCL) antibody
      following the third dose of adalimumab therapy for the treatment of
      spondyloarthropathy. This is the first case demonstrating that a short course of
      adalimumab therapy may induce immunoglobulin M aCL autoantibodies leading to APS.
      With the growing use of anti-TNF medications in immune-mediated and inflammatory
      diseases, adalimumab and other anti-TNF medications should be considered as a
      possible explanation for APS. 

PMID- 23559389
TI  - Parallel increase of circulating CXCL11 and CXCL10 in mixed cryoglobulinemia,
      while the proinflammatory cytokine IL-6 is associated with high serum Th2
      chemokine CCL2.
AB  - The aim was to investigate circulating levels of interelukin (IL)-1beta, IL-6 and
      tumor necrosis factor (TNF)-alpha, chemokine (C-X-C motif) ligand (CXCL)10,
      CXCL11 and chemokine (C-C motif) ligand (CCL)2 in "mixed cryoglobulinemia and
      hepatitis C" (MC + HCV). Serum levels of CXCL11, IL-1beta, TNF-alpha, IL-6, and
      CCL2 were evaluated in 52 MC + HCV vs 52 sex- and age-matched controls to
      correlate them to the clinical features of mixed cryoglobulinemia. CXCL11 was
      significantly higher in MC + HCV than in controls (264 +/- 279 vs 70 +/- 16
      pg/mL, respectively; P = 0.0002; univariate analysis of variance (ANOVA)), in
      particular in 23 MC + HCV with active vasculitis vs those without (293 +/- 221 vs
      168 +/- 57 pg/mL, respectively; P < 0.001; ANOVA). Significantly high IL-1beta,
      IL-6, TNF-alpha, CXCL10, and CCL2 in MC + HCV vs healthy controls were confirmed.
      In a multiple linear regression model (CXCL11 or CCL2, vs age, alanine
      aminotransferase, IL-1beta, IL-6, TNF-alpha, and CXCL10), CXCL11 was
      significantly associated with high CXCL10 (P < 0.001), while CCL2 with high IL-6
      (P < 0.001). This study demonstrates in MC + HCV high serum levels of (a) T
      helper 1 chemokines, CXCL11 and CXCL10 (related to each other) and (b)
      proinflammatory cytokines IL-6 and CCL2 (related to each other).

PMID- 23559390
TI  - Outcome of reactive arthritis after an extensive Finnish waterborne
      gastroenteritis outbreak: a 1-year prospective follow-up study.
AB  - The purpose of the study was to assess the 1-year outcome of definitive reactive
      arthritis (ReA) after a waterborne outbreak. A cohort of 21 patients (15 females
      and 6 males, median age 54 years) with ReA related to an extensive waterborne
      outbreak in Finland was clinically followed-up by rheumatologists with visits at
      baseline, at 1 month and 3, 6 and 12 months. Although the outcome was in general
      favourable, 1/3 of the patients had chronic course; 7 (33 %) of the 21 patients
      needed disease-modifying anti-rheumatic drugs (DMARDs) and even 8 (38 %) of them
      used glucocorticoids at 12 months. Four (19 %) were using non-steroidal anti
      inflammatory drugs and nine (43 %) other analgesics. Many patients had articular
      pain and impaired physical function still at 12 months, even though inflammatory
      parameters and the number of swollen joints were low. Only one patient (5 %) was
      human leucocyte antigen-B27-positive. She had the most severe ReA and also
      additional infectious arthritis caused by Salmonella serotype enteritidis leading
      to osteonecrosis of her hip joint with subsequent need for arthroplasty. ReA as
      observed in our study was overall fairly mild, but in many individuals,
      postinfectious arthralgia and DMARD use continued at least up to 1 year.

PMID- 23559391
TI  - Prostate cancer screening in black men--new questions, few answers.

PMID- 23559392
TI  - Characterization of neuroblastoma bone invasion/metastasis in established bone
      metastatic model of SY5Y and KCNR cell lines.
AB  - OBJECTS: To determine the mechanism of neuroblastoma (NB) bone
      invasion/metastasis, it is necessary to investigate the bone invasion/metastasis
      related factors in the bone invasion/metastasis process. Some evidence has
      suggested that various proteins were involved in bone osteolytic response. The
      invasion/metastasis property and gene expression of NB, however, are still
      unknown. METHODS: Single-cell suspensions of SY5Y and KCNR cells were injected
      directly into the femur of nude mice. Radiological and histological analyses,
      immunohistochemistry analyses, and western blot assay were performed to
      characterize bone metastasis mechanism in these bone metastasis models. RESULTS:
      SY5Y and KCNR NB cells result in osteolytic responses in bone metastasis model.
      Osteoprotegerin (OPG), receptor activator of NF-kappaB ligand (RANKL),
      parathyroid hormone-related peptide (PTHrP), endothelin 1 (ET-1), and CXCR4 were
      examined and compared among in vitro, in vivo, and normal bone, respectively.
      PTHrP, OPG, RANKL, and ET-1 except CXCR4 in SY5Y and KCNR NB cells xenografts
      were strikingly upregulated compared with normal bone and NB cells. However,
      significantly stronger expression of PTHrP and RANKL was presented than ET-1 and
      OPG; furthermore, the ratios of expression of PTHrP, RANKL to OPG, and ET-1 were
      also markedly increased in vivo versus in vitro. CONCLUSIONS: Our study provided
      evidence that NB cell may enhance bone invasion through PTHrP, OPG, RANKL, and ET
      1, especially PTHrP and RANKL which may display stronger effects. CXCR4 appeared
      not participating in bone invasion, but in tumor growth, and homing to bone.
      Targeting PTHrP, OPG, ET-1, and RANKL may provide a new insight and method for
      patient therapy by inhibiting NB bone metastasis and invasiveness.

PMID- 23559393
TI  - Proteus syndrome revealing itself after the treatment of a bilateral subdural
      haematoma.
AB  - INTRODUCTION: Hypertrophy of the calvarium has different aetiologies, among them
      the rare Proteus syndrome. CASE REPORT: We report here the case of a young girl
      initially treated for relapsing right then left large chronic subdural haematoma,
      who progressively developed craniofacial hypertrophy consistent with the
      diagnosis of Proteus syndrome. Calvarium hypertrophy was shaved and remodelled
      combining midface advancement, essentially for cosmetic purposes. During the
      first calvarium remodelling, important bleeding of the bone required large volume
      of blood replacement. Haemostasis workup revealed platelets aggregation
      anomalies. Bleeding issues during subsequent surgeries were controlled with
      tranexamic acid and desmopressin acetate. DISCUSSION: Other manifestations of
      Proteus syndrome, such as a right hypertrophy of the face with hypoplasia of its
      middle third, a pigmented epidermal nevus and asymmetric limbs and scoliosis,
      appeared progressively over time. Blood and fibroblast phosphatase and tensin
      homolog mutation was not found. CONCLUSION: Literature review of operated
      patients with Proteus syndrome did not reveal an association with platelets
      anomalies. A complete haemostasis workup following this unexpected haemorrhagic
      complication is recommended for this rare pathology.

PMID- 23559394
TI  - Intramedullary spinal cord abscess as complication of lumbar puncture: a case
      based update.
AB  - INTRODUCTION: Although lumbar puncture (LP) is a relatively straightforward
      procedure and is usually associated with low morbidity, rare and significant
      neurological complications can occur. Intramedullary spinal cord abscess (ISCA)
      after lumbar puncture is one of these serious complications; however, this
      complication has not yet been reported in children. CASE REPORT: After 27 days in
      another medical facility, a 1-year-old girl was admitted to our hospital with a
      diagnosis of fever of unknown origin. Prior to the second admission, she had
      undergone multiple traumatic LP attempts. The patient was referred to our
      institution with progressive and ascending weakness. Three days later, this
      weakness involved all of the patient's four limbs. A LP was performed and showed
      purulent cerebrospinal fluid (CSF). An emergent spinal magnetic resonance imaging
      was performed and revealed an intramedullary lesion extending from the T2 to L3
      level. Broad-spectrum antibiotics and steroids were administered to the patient,
      and a T2-L3 laminectomy was performed. The postoperative course was uneventful,
      but a neurologic deficit, including lower limb paralysis, remained. CONCLUSION:
      The index of suspicion for a pyogenic infection of the intramedullary space
      should be higher if progressive flaccid paralysis develops within a few days
      after a lumbar procedure. Nevertheless, the diagnosis may be challenging due to
      the rarity of this condition. Any misdiagnosis or delay of adequate treatment may
      lead to unfavorable outcomes.

PMID- 23559395
TI  - Can we safely administer the recommended dose of phenobarbital in very low birth
      weight infants?
AB  - AIM: We investigated whether the recommended phenobarbital loading dose of 15-20
      mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low
      birth weight preterm newborns with seizures. METHODS: Twenty-four convulsive
      preterms of <1,500 g were enrolled in the study. Phenobarbital was administered
      intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After
      24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection.
      Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital
      loading dose was administered, immediately before the next phenobarbital dose was
      injected. RESULTS: None of the cases had plasma phenobarbital concentrations
      above the therapeutic upper limit of 40 MUg/mL on the 2nd hour; one case (4.7%),
      on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17
      cases (70.8%), on the 96th hour. A negative correlation was detected between the
      serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036;
      r, -0.608) and 96th hour (p, 0.043; r, -0.769). CONCLUSIONS: We suggest that
      particular attention should be done while administering phenobarbital in
      preterms, as blood levels of phenobarbital are higher than the reference ranges
      that those are often reached with the recommended doses in these groups of
      babies.

PMID- 23559396
TI  - Large parietal midline defect with unusual ridge-like structure at the rim and
      persistent falcine sinus.
AB  - BACKGROUND: Midline cranial defects can be divided into lesions with intracranial
      tissue herniation (cranium bifidum cysticum) and lesions mainly with ossification
      failure (cranium bifidum occultum). Herniated cephaloceles mostly require
      surgical resection, while persisted parietal foramina might become smaller with
      age. CLINICAL CASE: Here, we report a neonate with large symmetric midline skull
      defect at high parietal area. A mild bulging mass was noticed. Interestingly,
      unlike sac herniation, it was surrounded by bony ridges extended from the rim of
      the calvarial defect, which suggests aberrant ossification. Persistent falcine
      sinus was also detected. At the corrected age of 11 months, the size of the skull
      defect had decreased spontaneously, favoring the diagnosis of parietal bone
      ossification defect. Potential mechanisms resulting in the special appearance of
      skull bone were discussed. CONCLUSION: Incomplete closing of the parietal
      foramina might be expected due to the aberrant ridge formation. We suggest
      protective measures for the calvarial defect.

PMID- 23559397
TI  - Important controversies associated with isotretinoin therapy for acne.
AB  - Isotretinoin is a remarkably effective drug for severe, recalcitrant acne
      vulgaris. Soon after the drug's release in the early 1980s, a number of important
      adverse effects were reported subsequently leading to a variety of medical and
      medicolegal controversies. Three of these controversies will be highlighted
      concerning the putative role of isotretinoin in (1) depression and suicide, (2)
      inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It
      appears that a very small subset of patients receiving isotretinoin for acne are
      at risk for depression, which is very manageable provided there is adequate
      patient awareness of the possibility, maximum communication between the patient
      and physician, and cessation of therapy if clinically important depression occurs
      (after which the depression rapidly resolves in a week or less). Multiple
      controlled studies actually suggest a very favorable effect of isotretinoin on
      depression and anxiety common in the population requiring isotretinoin. With
      regard to inflammatory bowel disease, in just one study, only ulcerative colitis
      association with isotretinoin reached statistical significance. The actual
      incidence of this association is strikingly low. Finally, it is clear that even
      the most recent pregnancy prevention program (iPledge) is no more successful than
      prior programs; there will likely always be a small number of female patients
      becoming pregnant while receiving isotretinoin for acne vulgaris.

PMID- 23559398
TI  - [Pediatric germ cell tumours].
AB  - Germ cell tumours include a group of highly heterogeneous tumours regarding to
      their clinical and histological appearance. Altogether, they represent 3% of
      cancers diagnosed in children and adolescent younger than 15 years. A bimodal age
      distribution is observed with a small peak during infancy and a larger peak after
      puberty. Non-seminomateous germ cell tumours are largely predominant as compared
      to seminomateous tumours, rarely seen before puberty. During infancy,
      sacrococcygeal locations predominate with either teratomas in neonates or yolk
      sac tumours in infants above three months. In adolescents, mixed germ cell
      tumours predominate with either gonadal, mediastinal or intracranial tumour.
      Surgical resection of the tumour is fundamental and must be carcinologic and
      conservative at the same time. Neoadjuvant chemotherapy may help to decrease the
      volume of the tumour making possible a delayed sparing surgery. Indeed, except
      for teratomas, these tumours are highly sensitive to chemotherapy, in particular
      to platinum salts. Prognosis is good even in metastatic diseases. This raises the
      question of a therapeutic de-escalation in an attempt to decrease long-term
      toxicity, in particular audiologic and renal impairment. On the opposite,
      recurrent or refractory diseases after chemotherapy carry a dismal prognosis and
      therapeutic strategies remain to be defined in such situations.

PMID- 23559399
TI  - Program fullerene: a software package for constructing and analyzing structures
      of regular fullerenes.
AB  - Fullerene (Version 4.4) is a general purpose open-source program that can
      generate any fullerene isomer, perform topological and graph theoretical
      analysis, as well as calculate a number of physical and chemical properties. The
      program creates symmetric planar drawings of the fullerene graph and generates
      accurate molecular 3D geometries by way of force-field optimization, serving as a
      good starting point for further quantum theoretical treatments. It includes a
      number of fullerene-to-fullerene transformations, such as Goldberg-Coxeter
      transforms, Stone-Wales transforms, Endo-Kroto, Yoshida-Fowler, and Brinkmann
      Fowler vertex insertions. The program is written in standard Fortran and C++ and
      can easily be installed in a Linux or UNIX environment.

PMID- 23559400
TI  - Tissue at risk in acute stroke patients treated beyond 8 h after symptom onset.
AB  - INTRODUCTION: The decision on thrombolytics administration is usually based on a
      generalized, rigid time-based rule rather than an individualized evaluation of
      the "tissue at risk of infarction" which is the target of the recanalization
      therapies. The goals of our article are to assess whether there is tissue at risk
      of infarction in a group of acute stroke patients treated beyond 8 h after
      symptom onset and to investigate the baseline imaging and clinical features that
      predict the fate of this tissue at risk. METHODS: We retrospectively reviewed a
      series of patients with acute ischemic stroke treated with endovascular
      recanalization therapies beyond 8 h after symptom onset. The tissue at risk was
      calculated as the difference between the infarct volumes on baseline and follow
      up imaging (infarct growth). We analyzed the epidemiological distribution of
      infarct growth, and we performed a multivariate regression analysis to identify
      the baseline variables that predict infarct growth. RESULTS: Our study group
      included 75 patients (65 +/- 13.8 years, baseline National Institutes of Health
      Stroke Scale 14 +/- 4.9, time to treatment 15.2 +/- 8.7 h). The mean infarct
      growth was 78.6 +/- 95.0 cc (p < 0.001), and, overall, the infarct growth was
      greater when the baseline volume of infarct tissue was small (p < 0.001) and in
      the case of a unsuccessful arterial recanalization (p = 0.001). CONCLUSIONS:
      There is potentially salvageable ischemic tissue at risk in acute stroke patients
      treated beyond 8 h after symptom onset.

PMID- 23559401
TI  - Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic
      syndrome patients with severe neurological symptoms but no changes in
      conventional MRI.
AB  - INTRODUCTION: Severe neurological symptoms in Shiga toxin-producing Escherichia
      coli infection associated hemolytic-uremic syndrome (STEC-HUS) are often
      accompanied by none or only mild alterations of cerebral magnetic resonance
      imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal
      cerebral pathological alterations invisible for conventional MRI. METHODS: In
      nine patients with STEC-HUS associated severe neurological symptoms but
      inconspicuous cerebral MRI findings maps of the parameters T2 relaxation time,
      relative proton density (PD), apparent diffusion coefficient (ADC), and
      fractional anisotropy (FA) were generated. Quantitative values of these
      parameters were measured at the basal ganglia, thalamus, and white matter of the
      frontal and parietal lobe and compared to those of nine age- and sex-matched
      controls. RESULTS: Significant T2 prolongation (p < 0.01) was found in the basal
      ganglia of all patients compared to controls. PD and ADC were not significantly
      altered. A significant reduction of FA in patients was seen at caput nuclei
      caudati (p < 0.01). CONCLUSION: Prolonged T2 relaxation time indicates cerebral
      microstructural damages in these patients despite their inconspicuous MRI
      findings. T2 relaxometry could be used as a complementary tool for the assessment
      of metabolic-toxic brain syndromes.

PMID- 23559402
TI  - Polymorphisms influencing olanzapine metabolism and adverse effects in healthy
      subjects.
AB  - OBJECTIVE: The pharmacokinetics of olanzapine and response to treatment could be
      affected by polymorphisms in genes coding for drug-metabolizing enzymes,
      transporters, or receptors. The aim of this study was to identify genetic markers
      predictive of pharmacokinetics, pharmacodynamics, and adverse effects of
      olanzapine. METHODS: Sixty-three healthy volunteers receiving a single 5-mg oral
      dose of olanzapine were genotyped for 39 genetic variants that could be related
      to the response to olanzapine. All genetic variants were analyzed by PharmaChip,
      but DRD2 Taq1A polymorphism was determined by real-time polymerase chain
      reaction. Olanzapine was measured using high-performance liquid chromatography
      combined with tandem mass spectrometry. The relationship of gender and
      polymorphisms with olanzapine pharmacokinetics, the change in prolactin levels,
      and the incidence of adverse effects were evaluated by multiple regression
      analysis. RESULTS: The pharmacokinetics of olanzapine was influenced by
      polymorphisms in CYP3A5, GSTM3, and GRIN2B. Prolactin levels were affected by
      gender and polymorphisms in DRD2 and 5-HTR2A. Polymorphisms in CYP2C9, TPMT,
      UGT1A1, MDR1, and 5-HTR2A were related to some adverse effects of olanzapine.
      CONCLUSIONS: Several polymorphisms can explain differences in the
      pharmacokinetics, pharmacodynamics, and safety of olanzapine in healthy subjects.
      Whether these genetic factors influence the risk of therapeutic failure or
      tolerability in patients remains to be established.

PMID- 23559403
TI  - Continuous in vivo blood pressure measurements using a fully implantable wireless
      SAW sensor.
AB  - In this paper, the development of a fully implantable wireless sensor able to
      provide continuous real-time accurate pressure measurements is presented. Surface
      Acoustic Wave (SAW) technology was used to deposit resonators on crystalline
      quartz wafers; the wafers were then assembled to produce a pressure sensitive
      device. Excitation and reading via a miniature antenna attached to the pressure
      sensor enables continuous external interrogation. The main advantages of such a
      configuration are the long term stability of quartz and the low power necessary
      for the interrogation, which allows 24/7 interrogation by means of a hand-held,
      battery powered device. Such data are of vital importance to clinicians
      monitoring and treating the effects of hypertension and heart failure. A
      prototype was designed and tested using both a bio-phantom test rig and an animal
      model. The pressure traces for both compare very well with a commercially
      available catheter tip pressure transducer. The work presented in this paper is
      the first known wireless pressure data from the left ventricle of the heart of a
      living swine. 

PMID- 23559404
TI  - Microengineered tumor models: insights & opportunities from a physical sciences
      oncology perspective.
AB  - Prevailing evidence has established the fundamental role of microenvironmental
      conditions in tumorigenesis. However, the ability to identify, interrupt, and
      translate the underlying cellular and molecular mechanisms into meaningful
      therapies remains limited, due in part to a lack of organotypic culture systems
      that accurately recapitulate tumor physiology. Integration of tissue engineering
      with microfabrication technologies has the potential to address this challenge
      and mimic tumor heterogeneity with pathological fidelity. Specifically, this
      approach allows recapitulating global changes of tissue-level phenomena, while
      also controlling microscale variability of various conditions including
      spatiotemporal presentation of soluble signals, biochemical and physical
      characteristics of the extracellular matrix, and cellular composition. Such
      platforms have continued to elucidate the role of the microenvironment in cancer
      pathogenesis and significantly improve drug discovery and screening, particularly
      for therapies that target tumor-enabling stromal components. This review
      discusses some of the landmark efforts in the field of micro-tumor engineering
      with a particular emphasis on deregulated tissue organization and mass transport
      phenomena in the tumor microenvironment. 

PMID- 23559405
TI  - Acute and chronic administration of the branched-chain amino acids decreases
      nerve growth factor in rat hippocampus.
AB  - Maple syrup urine disease (MSUD) is a neurometabolic disorder caused by
      deficiency of the activity of the mitochondrial enzyme complex branched-chain
      alpha-keto acid dehydrogenase leading to accumulation of the branched-chain amino
      acids (BCAA) and their corresponding branched-chain alpha-keto acids. In this
      study, we examined the effects of acute and chronic administration of BCAA on
      protein levels and mRNA expression of nerve growth factor (NGF) considering that
      patients with MSUD present neurological dysfunction and cognitive impairment.
      Considering previous observations, it is suggested that oxidative stress may be
      involved in the pathophysiology of the neurological dysfunction of MSUD. We also
      investigated the influence of antioxidant treatment (N-acetylcysteine and
      deferoxamine) in order to verify the influence of oxidative stress in the
      modulation of NGF levels. Our results demonstrated decreased protein levels of
      NGF in the hippocampus after acute and chronic administration of BCAA. In
      addition, we showed a significant decrease in the expression of ngf in the
      hippocampus only following acute administration in 10-day-old rats.
      Interestingly, antioxidant treatment was able to prevent the decrease in NGF
      levels by increasing ngf expression. In conclusion, the results suggest that BCAA
      is involved in the regulation of NGF in the developing rat. Thus, it is possible
      that alteration of neurotrophin levels during brain maturation could be of
      pivotal importance in the impairment of cognition provoked by BCAA. Moreover, the
      decrease in NGF levels was prevented by antioxidant treatment, reinforcing that
      the hypothesis of oxidative stress can be an important pathophysiological
      mechanism underlying the brain damage observed in MSUD. 

PMID- 23559407
TI  - Retinorecipient areas in the diurnal murine rodent Arvicanthis niloticus: A
      disproportionally large superior colliculus.
AB  - The Nile grass rat (Arvicanthis niloticus) has a high proportion of cone
      photoreceptors (~30-40%) compared with that in the common laboratory mouse and
      rat (~1-3%) and may prove a preferable murine model with which to study cone
      driven information processing in retina and primary visual centers. However,
      other than regions involved in circadian control, little is known about the
      retinorecipient structures in this rodent. We undertook a detailed analysis of
      the retinal projections as revealed after intravitreal injection of the
      anterograde tracer cholera toxin subunit B. Retinal efferents were evaluated in
      45 subcortical structures. Contralateral projections were always dominant. Major
      contralateral inputs consisted of the suprachiasmatic nucleus, dorsolateral
      geniculate nucleus (dLGN), intergeniculate leaflet, ventral geniculate nucleus
      (magnocellular part), lateroposterior thalamic nucleus, all six pretectal nuclei,
      superficial layers of the superior colliculus (SC), and the main nuclei of the
      accessory optic system. Terminals from the contralateral eye were also localized
      in an unnamed field rostromedial to the dLGN as well as in the subgeniculate
      thalamic nucleus. Ipsilateral inputs were found mainly in the suprachiasmatic
      nucleus, dLGN, intergeniculate leaflet, internal sector of the magnocellular part
      of the ventral geniculate nucleus, olivary pretectal nucleus, and SC optic layer.
      Retinal afferents were not detected in the basal forebrain or the dorsal raphe
      nucleus. Morphometric measurements revealed that the superficial layers of the SC
      are disproportionately enlarged relative to other retinorecipient regions and
      brain size compared with rats and mice. We suggest that this reflects the
      selective projection of cone-driven retinal ganglion cells to the SC. J. Comp.
      Neurol. 521:1699-1726, 2013. (c) 2012 Wiley Periodicals, Inc.

PMID- 23559408
TI  - Hydrolysis profiling: an in vitro methodology to predict in vivo absorption time.
AB  - An in vitro method was developed for estimating in vivo degradation time of
      sutures made from synthetic bioresorbable polyesters. Model compounds and a
      number of commercially available bioresorbable suture products were used to
      establish the applicability of this hydrolysis profile methodology. Hydrolysis
      profiles on tested bioresorbable sutures were determined as a function of size
      and chemical composition. This method of accelerated absorption testing may
      shorten product development time and reduce the need for animal testing. In
      addition, the methodologies presented have the potential to provide insight into
      the loss of mechanical properties with time.

PMID- 23559406
TI  - Muscarinic cholinergic receptor M1 in the rat basolateral amygdala:
      ultrastructural localization and synaptic relationships to cholinergic axons.
AB  - Muscarinic neurotransmission in the anterior basolateral amygdalar nucleus (BLa)
      mediated by the M1 receptor (M1R) is critical for memory consolidation. Although
      knowledge of the subcellular localization of M1R in the BLa would contribute to
      an understanding of cholinergic mechanisms involved in mnemonic function, there
      have been no ultrastructural studies of this receptor in the BLa. In the present
      investigation, immunocytochemistry at the electron microscopic level was used to
      determine which structures in the BLa express M1R. The innervation of these
      structures by cholinergic axons expressing the vesicular acetylcholine
      transporter (VAChT) was also studied. All perikarya of pyramidal neurons were
      labeled, and about 90% of dendritic shafts and 60% of dendritic spines were M1R+.
      Some dendrites had spines suggesting that they belonged to pyramidal cells,
      whereas others had morphological features typical of interneurons. M1R
      immunoreactivity (M1R-ir) was also seen in axon terminals, most of which formed
      asymmetrical synapses. The main targets of M1R+ terminals forming asymmetrical
      synapses were dendritic spines, most of which were M1R+. The main targets of M1R+
      terminals forming symmetrical synapses were M1R+ perikarya and dendritic shafts.
      About three-quarters of VAChT+ cholinergic terminals formed synapses; the main
      postsynaptic targets were M1R+ dendritic shafts and spines. In some cases M1R-ir
      was seen near the postsynaptic membrane of these processes, but in other cases it
      was found outside of the active zone of VAChT+ synapses. These findings suggest
      that M1R mechanisms in the BLa are complex, involving postsynaptic effects as
      well as regulating release of neurotransmitters from presynaptic terminals.

PMID- 23559410
TI  - Energy expenditure in rock/pop drumming.
AB  - Despite the vigorous nature of rock/pop drumming, there are no precise data on
      the energy expenditure of this activity. The aim of this study was to quantify
      the energy cost of rock/pop drumming. Fourteen male drummers (mean+/-SD; age 27+/
      8 yrs.) completed an incremental drumming test to establish the relationship
      between energy expenditure and heart rate for this activity and a ramped cycle
      ergometer test to exhaustion as a criterion measure for peak values (oxygen
      uptake and heart rate). During live concert performance heart rate was
      continuously measured and used to estimate energy expenditure (from the energy
      expenditure vs. heart rate data derived from the drumming test). During concert
      performance, estimated energy expenditure (mean+/-SD) was 623+/-168 kcal.h-1
      (8.1+/-2.2 METs) during performances of 38.6+/-15.6 min, and drummers achieved a
      peak heart rate of 186+/-16 b.min-1. During the drumming test participants
      attained 78.7+/-8.3% of the cycle ergometer peak oxygen uptake. Rock/pop drumming
      represents a relatively high-intensity form of physical activity and as such
      involves significant energy expenditure. Rock/pop drumming should be considered
      as a viable alternative to more traditional forms of physical activity.

PMID- 23559409
TI  - Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with
      a nephronophthisis-related ciliopathy.
AB  - Nephronophthisis-related ciliopathies (NPHP-RC) are autosomal-recessive cystic
      kidney diseases. More than 13 genes are implicated in its pathogenesis to date,
      accounting for only 40 % of all cases. High-throughput mutation screenings of
      large patient cohorts represent a powerful tool for diagnostics and
      identification of novel NPHP genes. We here performed a new high-throughput
      mutation analysis method to study 13 established NPHP genes (NPHP1-NPHP13) in a
      worldwide cohort of 1,056 patients diagnosed with NPHP-RC. We first applied
      multiplexed PCR-based amplification using Fluidigm Access-ArrayTM technology
      followed by barcoding and next-generation resequencing on an Illumina platform.
      As a result, we established the molecular diagnosis in 127/1,056 independent
      individuals (12.0 %) and identified a single heterozygous truncating mutation in
      an additional 31 individuals (2.9 %). Altogether, we detected 159 different
      mutations in 11 out of 13 different NPHP genes, 99 of which were novel.
      Phenotypically most remarkable were two patients with truncating mutations in
      INVS/NPHP2 who did not present as infants and did not exhibit extrarenal
      manifestations. In addition, we present the first case of Caroli disease due to
      mutations in WDR19/NPHP13 and the second case ever with a recessive mutation in
      GLIS2/NPHP7. This study represents the most comprehensive mutation analysis in
      NPHP-RC patients, identifying the largest number of novel mutations in a single
      study worldwide. 

PMID- 23559411
TI  - Modulation of follistatin and myostatin propeptide by anabolic steroids and
      gender.
AB  - The purpose of this pilot study was to investigate the impact of training,
      anabolic steroids and endogenous hormones on myostatin-interacting proteins in
      order to identify manipulations of myostatin signalling. To identify whether
      analysis of the myostatin interacting proteins follistatin and myostatin
      propeptide is suitable to detect the abuse of anabolic steroids, their serum
      concentrations were monitored in untrained males, bodybuilders using anabolic
      steroids and natural bodybuilders. In addition, we analysed follistatin and
      myostatin propeptide serum proteins in females during menstrual cycle. Our
      results showed increased follistatin concentrations in response to anabolic
      steroids. Furthermore, variations of sex steroid levels during the menstrual
      cycle had no impact on the expression of follistatin and myostatin propetide. In
      addition, we identified gender differences in the basal expression of the
      investigated proteins. In general, follistatin and myostatin propeptide
      concentrations were relatively stable within the same individual both in males
      and females. In conclusion, the current findings provide an insight into gender
      differences in myostatin-interacting proteins and their regulation in response to
      anabolic steroids and endogenous hormones. Therefore our data provide new aspects
      for the development of doping prevention strategies. 

PMID- 23559412
TI  - Strength-training with whole-body vibration in long-distance runners: a
      randomized trial.
AB  - A parallel group randomized trial was designed to analyze the impact of 6 weeks
      of strength training programs performed with or without whole-body vibration on
      muscular and endurance performance parameters in long-distance runners. 22
      endurance runners were allocated into strength with whole-body vibration (n=8),
      without (n=8), and control (n=6) groups. Before and after the experimental period
      the subjects performed the following tests: a) maximum dynamic strength test, b)
      maximal incremental treadmill test, and c) time to exhaustion at velocity
      corresponding to maximal oxygen uptake. The fractions of the aerobic and
      anaerobic contribution in time to exhaustion test were also calculated. Both
      strength trained groups showed a similar increase in maximum dynamic strength
      (~18%). The aerobic contribution was enhanced for strength training group without
      whole-body vibration (~25%) after experimental period. No statistical differences
      were observed in any other variable. These results suggest that 6 weeks of
      strength training performed with or without whole-body vibration improve
      similarly the maximum dynamic strength in long-distance runners. In addition,
      both training modes studied had no deleterious effects on the traditional
      parameters of endurance performance, traditional strength training program
      results in increased aerobic contribution during high-intensity aerobic exercise.

PMID- 23559413
TI  - Cardiorespiratory fitness associates with metabolic risk independent of central
      adiposity.
AB  - This study sought to analyze the associations between cardiorespiratory fitness
      (CRF), waist circumference (WC) and metabolic risk in children and adolescents.
      Participants were 633 subjects (58.7% girls) ages 10-18 years. Metabolic risk
      score (MRS) was calculated from HDL-cholesterol, triglycerides, fasting glucose
      and mean arterial pressure. MRS was dichotomized into low and high metabolic risk
      (HMRS). CRF was defined as the maximal oxygen uptake (VO2max) estimated from the
      20 m Shuttle Run Test. The first quartile of CRF was set as the low fitness
      group. The fourth quartile of WC was defined as high central adiposity. With
      adjustments for age, sex and WC, CRF was correlated with MRS (r=-0.095; p<0.05).
      WC was correlated with MRS (r=0.150; p<0.001) after adjustments for age, sex and
      CRF. Participants who had low fitness levels, presented higher levels of MRS
      (p<0.001) compared to those who were fit, even after adjustment for age, sex and
      WC. In comparison with subjects who were fit with normal central adiposity, an
      increased odds ratio (OR) for being at HMRS was found for participants who were
      of low fitness level with high central adiposity (OR=2.934; 95%CI= 1.690-5.092)
      and for those who were of low fitness with normal central adiposity (OR=2.234;
      95%CI=1.116-4.279). Results suggest that CRF relates to MRS independently of
      central adiposity.

PMID- 23559414
TI  - Sacral neuromodulation for fecal incontinence and "low anterior resection
      syndrome" following neoadjuvant therapy for rectal cancer.
AB  - BACKGROUND: It was the aim of this prospective study to analyze both feasibility
      and effectiveness of sacral neuromodulation for fecal incontinence and "low
      anterior resection syndrome" following neoadjuvant therapy for rectal cancer.
      METHODS: All patients who underwent sacral neuromdulation following neoadjuvant
      therapy for rectal cancer (preoperative radiochemotherapy, oncologic rectal
      resection with total mesorectal excision) were prospectively enrolled in the
      study. Only patients with failure of conservative treatment and without any
      evidence of residual or recurrent tumor disease were candidates for sacral
      neuromdulation which was performed by a two-stage procedure (diagnostic
      percutaneous test stimulation followed by definite implant). In addition to
      feasibility, primary end points included success (reduction of incontinent
      episodes), continence and defecation status (assessed by Cleveland Clinic
      Incontinence Score and Altomare score), and quality of life (EQ-5D). Anal
      manometry was performed preoperative and at 12-month follow-up. Follow-up
      information was derived from clinical examination 3, 6, and 12 months
      postoperatively. RESULTS: Nine patients (three females, six males) with a mean
      age of 61 years underwent sacral neuromodulation following neoadjuvant therapy
      for rectal cancer. Implantation rate was 100 %. No septic morbidity was observed.
      After a mean follow-up of 12 months, mean Cleveland Clinic Incontinence Score was
      reduced from 18.2 to 6.0 (p < 0.01). Incontinence episodes were significantly
      reduced from 7 to 0.5 (per day) and 20 to 8 (per week). Fecal urgency, fragmented
      defecation, and soiling were improved or resolved in two thirds. Altomare score
      was significantly reduced from 21.0 to 9.3 (p < 0.01). Anorectal manometry did
      not correlate with clinical success. Quality of life was significantly improved
      (EQ-5D generic: 0.42 vs. 0.74, EQ-5D-VAS score: 20 vs. 90, p < 0.01).
      CONCLUSIONS: Preliminary results of sacral neuromodulation in patients with fecal
      incontinence and symptoms of "low anterior resection syndrome" are promising and
      enrich the therapeutic modalities if conservative management has failed.

PMID- 23559415
TI  - Oxidative DNA damage and beta-catenin expression in colorectal cancer evolution.
AB  - PURPOSE: Oxidative DNA damage is one of the mechanisms associated to initial
      colorectal carcinogenesis, but how it interacts with beta-catenin, an adherence
      protein related to cancer evolution, is not clear. This study investigates the
      relationship between oxidative DNA damage and beta-catenin expression in normal
      mucosa and colon tumor tissue (adenoma and adenocarcinoma) in colorectal
      adenocarcinoma evolution. METHOD: One hundred and 13 samples were studied.
      Hematoxylin-eosin determined histological grade. beta-Catenin expression was
      analyzed by immunohistochemistry. The oxidative DNA damage was evaluated using
      comet assay technique. The coefficient for rejection of the nullity hypothesis
      was taken to 5 %. Kruskal-Wallis, Spearman test, and partial correlation were
      used to analyze the data. RESULTS: There was oxidative DNA damage increase in
      colorectal cancer evolution (p < 0.01). Histological grade was correlated with
      oxidative DNA damage (p < 0.01). There were differences in beta-catenin
      expression among normal, adenoma, and adenocarcinoma tissue with progressive
      increase of beta-catenin expression (p < 0.00). Histological grade was correlated
      to beta-catenin expression (p < 0.00). There was a relationship (p < 0.00)
      between beta-catenin and histological grade while controlling for the effect of
      oxidative DNA damage. CONCLUSION: The findings of this study make it possible to
      establish a relationship between oxidative DNA damage and beta-catenin expression
      in normal mucosa and colorectal tumor tissue. Additionally, they show a causal
      relationship between variations of beta-catenin in different tissues analyzed
      while controlling for the effect of oxidative DNA damage.

PMID- 23559416
TI  - Proteomics of human seminal plasma: identification of biomarker candidates for
      fertility and infertility and the evolution of technology.
AB  - Proteomics is a research area that has developed rapidly in the last decade. It
      studies the large-scale characterization of the full protein components of a
      cell, a tissue, or a biological fluid. In the last decade, clinical proteomics
      has developed new technology and bioinformatics useful in identifying molecular
      markers of pathology; the next decade might be the era of proteomics. Seminal
      plasma (SP) represents a good sample for proteomic analysis in the evaluation of
      male fertility/infertility. SP is an acellular fluid conglomerate, comprised of
      contributions from the epididymis and accessory sexual glands. Human SP contains
      many proteins that are important to the successful fertilization of the oocyte by
      the spermatozoa. Proteomic studies have identified numerous seminal-specific
      proteins, and recent reports have provided a further understanding of their
      function with respect to male fertility. Upon further validation, these proteins
      may be useful in the clinical distinction between fertility and infertility. This
      article reviews the proteomic methods, such as one dimensional polyacrylamide gel
      electrophoresis (1D-PAGE), two-dimensional polyacrylamide gel electrophoresis (2D
      PAGE), and mass spectrometry (MS), employed to detect human SP markers involved
      in fertility and infertility. As such, proteomic studies will help the
      development of new techniques to identify novel biomarkers for a better clinical
      diagnosis and treatment of male infertility.

PMID- 23559417
TI  - Probing spatial distribution of alignment by deuterium NMR imaging.
AB  - Deuterium NMR imaging was used to evaluate the spatial distribution of the degree
      of alignment in different types of alignment media by monitoring the deuterium
      quadrupolar splitting using spatially resolved NMR techniques in conventional
      liquid state NMR instruments. These images allow the unambiguous distinction of
      magnetic field and alignment inhomogeneities present in partially aligned
      samples, revealing the underlying reasons for linebroadening within an alignment
      medium that cannot be explained by the sole analysis of 1D (2)H NMR spectra. For
      example, alignment inhomogeneities due to broken gels or the presence of
      concentration gradients in liquid crystalline solutions are clearly detected by
      the imaging methods proposed in this work.

PMID- 23559418
TI  - Making ends meet: chemically mediated circularization of recombinant proteins.
AB  - A selective N->S acyl transfer reaction facilitates semi-synthesis of the plant
      cyclotide kalata B1 from a linear precursor peptide of bacterial origin, through
      simple appendage of N-terminal cysteine and a thiol-labile C-terminal Gly-Cys
      motif. This constitutes the first synthesis of a ribosomally derived circular
      miniprotein, without recourse to protein splicing elements.

PMID- 23559419
TI  - Validation of sub-segmental visual scoring for the quantification of ischemic and
      nonischemic myocardial fibrosis using late gadolinium enhancement MRI.
AB  - PURPOSE: To determine the accuracy and reproducibility of late gadolinium
      enhancement (LGE) MRI scar quantification using visual sub-segmental analysis
      (VSSA) versus signal threshold-based analysis in ischemic and nonischemic
      cardiomyopathy. MATERIALS AND METHODS: One-hundred sixty-one patients with
      abnormal LGE imaging underwent VSSA and signal threshold-based analysis. VSSA was
      performed using a 68 sub-segmental model. Signal threshold-based analysis was
      performed using cutoffs of >=2, >=3, and >=5 standard deviations (SD) above the
      mean signal of normal myocardium. Comparison of VSSA and signal threshold-based
      analysis was performed by linear regression and Bland Altman plots. RESULTS:
      Seventy (44%) patients had ischemic scar, 76 (47%) had nonischemic scar, and 15
      (9%) had a combined pattern. Correlation coefficients for VSSA versus signal
      threshold-based analysis at >=2, >=3, and >=5SD thresholds were r = 0.63, r =
      0.79, r = 0.81 (P < 0.001) for all patients, r = 0.74, r = 0.81, r = 0.81 (P <
      0.001) in those with ischemic scar, and r = 0.46, r = 0.69, r = 0.72 (P < 0.001)
      in those with nonischemic scar. Bland Altman analysis revealed no significant
      bias in total scar volume among all patients (-4.3 +/- 7.9%), those with ischemic
      scar (-4.8 +/- 7.8%), or those with nonischemic scar (-2.6 +/- 7.6%). Intra
      observer and inter-observer variability of the VSSA technique was excellent with
      a mean difference in total percent scar of 0.3% (-8.3-8.9%) and -0.4% (-9.5
      8.5%), respectively. CONCLUSION: A VSSA-based model of myocardial scar
      quantification is accurate and reproducible in ischemic and nonischemic
      cardiomyopathy.

PMID- 23559420
TI  - Association between race and follow-up diagnostic care after a positive prostate
      cancer screening test in the prostate, lung, colorectal, and ovarian cancer
      screening trial.
AB  - BACKGROUND: Follow-through of a positive screening test is necessary to reap the
      potential benefits of cancer screening. Racial variation in follow-through
      diagnostic care may underlie a proportion of the known disparity in prostate
      cancer mortality. The authors used data from the screening arm of the Prostate,
      Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to determine whether
      race is associated with the use of follow-up diagnostic testing after a positive
      initial screening evaluation. METHODS: Men who had a prostate-specific antigen
      (PSA) level >4 ng/mL at any time during the study were included. The proportion
      of men who underwent follow-up evaluation with a repeat PSA, a prostate biopsy,
      or either test within 9 months was determined, and the authors tested for
      differences in follow-through according to race using mixed-effects multivariate
      models with a random effect for accrual site to account for clustering. Models
      were stratified according to age (<65 years and >=65 years). RESULTS: Among 6294
      men who had a PSA elevation during the study period, 70% underwent a repeat PSA
      or prostate biopsy within 9 months. Non-Hispanic black men aged <65 years had 45%
      lower odds of undergoing a repeat PSA test or prostate biopsy compared with non
      Hispanic white men (odds ratio, 0.55; 95% confidence interval, 0.37-0.82),
      whereas there was no racial difference in follow-through among older men.
      CONCLUSIONS: The current results suggest that limitations in access to care among
      non-Hispanic black men under the age of Medicare eligibility may underlie the
      paradoxically low use of follow-through diagnostic care among non-Hispanic black
      men in the United States.

PMID- 23559422
TI  - Assessment of competency in clinical measurement: comparison of two forms of
      sequential test and sensitivity of test error rates to parameter choice.
AB  - OBJECTIVE: To assess clinical measurement competency by two sequential test
      formulations [resetting sequential probability ratio test (R-SPRT) and learning
      curve cumulative summation (LC-CUSUM)]. DESIGN: Numerical simulation and
      retrospective observational study. SETTING: Obstetric ultrasound department.
      PARTICIPANTS: Cohorts of 10,000 simulated trainees and 62 obstetric sonographers
      training in nuchal translucency (NT) measurement at the 11-14-week pregnancy scan
      with limited case availability. INTERVENTION: Application of LC-CUSUM and R-SPRT
      to clinical measurement training. MAIN OUTCOME MEASURES: Proportions of real
      trainees achieving competency by LC-CUSUM and R-SPRT, proportions of simulated
      competent trainees not achieving competency (Type I error), proportions of
      simulated incompetent trainees achieving competency (Type II error), distribution
      of case number required to achieve competency (run length) and frequency of
      resets. RESULTS: For simulated cohorts, significant differences in run-length
      distribution and true test error rates were found between the R-SPRT and LC-CUSUM
      tests with equivalent parameters. Increasing the cases available to each trainee
      reduced the Type I error rate but increased the Type II error rate for both
      sequential tests for all choices of unacceptable failure rate. Discontinuities in
      the proportion of trainees expected to be test competent were found at critical
      values of unacceptable failure rate. CONCLUSIONS: With equivalent parameters, the
      R-SPRT and LC-CUSUM formulations of sequential tests produced different outcomes,
      demonstrating that the choice of test method, as well as the choice of
      parameters, is important in designing a training scheme. The R-SPRT detects
      incompetence as well as competence and may indicate need for further training.
      Simulations are valuable in estimating the proportions of trainees expected to be
      assessed as competent.

PMID- 23559423
TI  - Neurological letter from Zambia.

PMID- 23559424
TI  - Use of ab initio methods for the interpretation of the experimental IR
      reflectance spectra of crystalline compounds.
AB  - It is shown that ab initio simulation can be used as a powerful complementary
      tool in the interpretation of the experimental reflectance spectra R(nu) of
      crystalline compounds. Experimental frequencies and intensities are obtained from
      a best fit of R(nu) with a set of damped harmonic oscillators, whose number and
      initial position in frequency can dramatically influence the final results, as
      the parameters are strongly correlated. Computed ab initio values for frequencies
      and intensities are accurate enough to represent an excellent starting point for
      the best fit process. Moreover, at variance with respect to experiment,
      simulation permits to identify all the symmetry allowed modes, also when
      characterized by low intensity or when close to a very intense peak. Overall,
      simulation-aided analysis of experimental spectra prevents from classifying
      combination modes as fundamental modes and permits to discard artifacts due to
      superposition of bands, background, and noise. Finally, it allows to (almost)
      completely characterize the set of fundamental modes.

PMID- 23559421
TI  - A matter of balance: role of neurexin and neuroligin at the synapse.
AB  - Neurexins and neuroligins are synaptic cell adhesion molecules. Neurexins are
      primary located on the presynaptic membrane, whereas neuroligins are strictly
      postsynaptic proteins. Since their discovery, the knowledge of neurexins and
      neuroligins has expanded, implicating them in various neuronal processes,
      including the differentiation, maturation, stabilization, and plasticity of both
      inhibitory and excitatory synapses. Here, we review the most recent results
      regarding the structure and function of these cell adhesion molecules.

PMID- 23559425
TI  - Coelioscopic orchiectomy can be effectively and safely accomplished in
      chelonians.
AB  - Coelioscopic orchiectomy was performed in 27 male turtles (25 juvenile to adult
      red-eared sliders (Trachemys scripta elegans), one adult eastern painted turtle
      (Chrysems picta picta), and one juvenile male yellow-spotted Amazon River turtle
      (Podocnemis unifilis)). Orchiectomy was conducted under coelioscopic
      visualisation using ligation and transection of the mesorchium, or transection of
      the mesorchium with monopolar radiosurgical scissors. In 22 cases, bilateral
      orchiectomy was performed through a single incision; five turtles required
      bilateral incisions. All turtles recovered from anaesthesia. Nine turtles died
      within one year of surgery from conditions believed to be unrelated to surgery.
      One turtle was lost to follow-up. Seventeen turtles remain clinically healthy one
      to three years postoperatively. Coelioscopic orchiectomy provides a minimally
      invasive method for sterilisation of male chelonians and provides excellent
      visualisation during surgery. This technique is a useful model for the
      development of additional minimally invasive surgical techniques for chelonians.

PMID- 23559426
TI  - Dynamic ventrorostral displacement of the dorsal laryngeal mucosa in horses.
AB  - The objectives of this report were to describe the occurrence and features of
      dynamic ventrorostral displacement of the dorsal laryngeal mucosa (VRDDLM) in a
      group of Thoroughbred horses presented for investigation of poor performance
      and/or abnormal respiratory noise. Records from 600, dynamic, endoscopic
      examinations of the upper respiratory tract of horses were reviewed. Horses with
      VRDDLM were identified as those in which the dorsal laryngeal mucosa
      progressively obscured the interarytenoid notch and dorsoaxial portion of the
      corniculate processes of the arytenoid cartilages during high-speed exercise. The
      condition was recognised in 12 horses. Concurrent abnormalities of the
      respiratory tract of eight horses were also identified and included, axial
      deviation of the aryepiglottic folds, vocal cord prolapse, unilateral and
      bilateral ventromedial luxation of the apex of the corniculate process of the
      arytenoid cartilage, and intermittent dorsal displacement of the soft palate.
      VRDDLM is a rare abnormality of the upper portion of the respiratory tract of
      horses that may be associated with abnormal respiratory noise and potentially
      poor performance. The significance of the condition is not known, but the
      presence of this condition in combination with other, obstructive diseases of the
      equine airway warrants further investigation.

PMID- 23559427
TI  - Association of the dopamine beta-hydroxylase 19 bp insertion/deletion
      polymorphism with positive symptoms but not tardive dyskinesia in schizophrenia.
AB  - OBJECTIVE: Overactivity of dopaminergic neurotransmission is a putative mechanism
      of tardive dyskinesia (TD). Dopamine beta-hydroxylase (DBH) is a key enzyme in
      the conversion of dopamine to norepinephrine, and plasma DBH activity is altered
      in TD patients. This study examined whether the functional DBH 5'-Ins/Del
      polymorphism was associated with TD severity in Chinese patients with
      schizophrenia. METHODS: We compared the rate of this polymorphism in patients
      with (n = 312) and without TD (n = 435), and healthy controls (n = 625). The
      severity of TD was assessed using the Abnormal Involuntary Movement Scale (AIMS)
      and psychopathology using the Positive and Negative Syndrome Scale (PANSS).
      RESULTS: There were no significant differences in the distribution of the allele
      and genotype frequencies between the patients and controls, or between the
      patients with and without TD. Also, there was no significant difference in the
      AIMS total score between the three genotype groups. However, the PANSS positive
      symptom subscore was significantly higher in patients with Del/Del genotype (13.2
      +/- 5.2) than those with Ins/Del (11.2 +/- 4.9) and Ins/Ins (11.1 +/- 3.1)
      genotypes (both p < 0.05). CONCLUSION: These results suggest that although the
      DBH 5'-Ins/Del polymorphism was not associated with susceptibility to TD in
      patients with schizophrenia, it might be related to positive symptoms of
      schizophrenia.

PMID- 23559428
TI  - The identification of free cysteine residues within antibodies and a potential
      role for free cysteine residues in covalent aggregation because of agitation
      stress.
AB  - Human immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2) antibodies contain
      multiple disulfide bonds, which are an integral part of the structure and
      stability of the protein. Open disulfide bonds have been detected in a number of
      therapeutic and serum derived antibodies. This report details a method that
      fluorescently labels free cysteine residues, quantifies, and identifies the
      proteolytic fragments by liquid chromatography coupled to online mass
      spectrometry. The majority of the open disulfide bonds in recombinant and serum
      derived IgG1 and IgG2 antibodies were in the constant domains. This method was
      applied to the identification of cysteines in an IgG2 antibody that are involved
      in the formation of covalent intermolecular bonds because of the application of a
      severe agitation stress. The free cysteine in the CH 1 domain of the IgG2
      decreased upon application of the stress and implicates open disulfide bonds in
      this domain as the likely source of free cysteines involved in the formation of
      intermolecular disulfide bonds. The presence of comparable levels of open
      disulfide bonds in recombinant and endogenous antibodies suggests that open
      disulfide bonds are an inherent feature of antibodies and that the susceptibility
      of intermolecular disulfide bond formation is similar for recombinant and serum
      derived IgG antibodies.

PMID- 23559429
TI  - Toward single-walled carbon nanotube-gadolinium complex as advanced MRI contrast
      agents: pharmacodynamics and global genomic response in small animals.
AB  - Gadolinium nanoparticle-catalyzed single-walled carbon nanotubes (Gd-SWCNTs) have
      recently shown potential in vitro as high-performance T1 magnetic resonance
      imaging (MRI) contrast agents (CAs). Their preclinical safety assessment at
      nontoxic dosages is essential for MRI applications. Herein, the in vivo (in rats)
      pharmacodynamics of Gd-SWCNTs (water solubilized with the amphiphilic polymer PEG
      DSPE) at the organ, tissue, molecular, and genetic level is reported. Gd-SWCNT,
      commercially available iron catalyzed SWCNTs (Fe-SWCNTs, control 1) and PEG-DSPE
      (control 2) solutions were intravenously injected at a potential nontoxic
      therapeutic dose (0.5 mg/kg body weight, single bolus). Postinjection, bright
      field optical microscopy showed their macroscale distribution in lung, liver,
      kidney, brain, and spleen up to 5 days. Raman and transmission electron
      microscopy (TEM) showed their presence at the nanoscale within hepatocytes. Their
      effects on the host organ tissue, molecular, and genetic level were analyzed
      after 1, 5, 10, 20, and 30 days by histology, biomolecular [lipid peroxidation,
      plasma tumor necrosis factor TNF-alpha assay, microarrays] assays. The results
      indicate that Gd-SWCNTs neither cause any inflammation, nor damage to the above
      organs, nor any significant change in the lipid peroxidation or plasma
      proinflammatory cytokine (TNF-alpha) levels for all the groups at all time
      points. Global gene expression profile of liver (main organ for the metabolism)
      after day 1 treatment with Gd-SWCNTs shows that the gene regulation is directed
      toward maintaining normal homeostasis. The results taken together indicate that
      PEG-DSPE water-solubilized Gd-SWCNTs at potentially nontoxic dosages have
      pharmacodynamics similar to other commercially available Fe-SWCNTs and are
      suitable for future preclinical development as in vivo MRI CAs.

PMID- 23559430
TI  - [The management of the metastatic disease by the surgeons].
AB  - The high rate of recurrence after apparently complete surgery and/or complete
      clinical response to chemotherapy implies that most patients have undetected
      minimal residual disease. Novel techniques such as laparoscopic or laparotomic
      fluorescence may prove to be crucial in reassessing the definition of primary
      outcome in ovarian cancer management. For this purpose, the importance of
      fluorescence in the peroperative detection of human ovarian adenocarcinoma cells
      has to be validated in animal models prior to be used in clinic by determining
      its efficiency in detecting infra-millimetric tumor metastases. In the
      preclinical data presented, a fluorescent RAFT-(cRGD)4 tracer molecule
      (AngioStamp((r))) with a very high affinity for the alphavbeta3 integrin was
      used. Infrared fluorescence was visualized with Fluobeam((r)), an open
      fluorescent imaging system that could potentially be used in peroperative
      conditions in the future. We showed that this novel technique allowed the
      specific detection of residual tumor deposits and inframillimetric metastases in
      mice and dogs.

PMID- 23559432
TI  - [Evaluation of a child protecting team by an independent cooperation partner -
      suggestions for an optimized procedure].
AB  - Cooperation between different institutions in cases of child abuse is essential
      for the children and their families. The aim of this study is to evaluate the
      cooperation between the Child Protection Team (CPT) and the Youth Welfare Agency
      (YWF) in an academic teaching hospital. ISSUES: Is the child or the family
      already be known to the YWF? Was the suspicion of child abuse confirmed by the
      CPT? What impact did the CPT's report to the YWF have on the situation of the
      children, their families, and the members of the YWF?Between 1999 and 2009 196
      cases were investigated by the CPT; 80 of them had been reported to the YWF. In
      45 of the 80 cases, structured interviews were completed by the YWF social
      workers. In the remaining 35, the questionnaires were not fully completed (n=15),
      the responsible social workers not present (n=6), or data were not available due
      to change of -residence (n=14).Maltreatment was suspected in 21/45 (47%), child
      abuse in 7 (16%), child neglect in 12 (26%), and a combination of the above in 5
      (11%) children. Of the children, 26/45 (58%) were already known to the YWF before
      being contacted by the CPT, and in 34/45 (75%) children either institutions
      reported the case to the criminal prosecution authorities. Positive changes were
      seen in 35/45 (78%) children and in 19/45 (42%) families and the CPT's report was
      considered helpful for the social workers in 41/45 (91%) children.A CPT is able
      to correctly identify new cases of child abuse. The activity of the CPT has a
      positive influence on the situation of affected children, their families, and the
      respective staff members of the YWF.

PMID- 23559431
TI  - Nutrients intake as determinants of blood lead and cadmium levels in Colombian
      pregnant women.
AB  - OBJECTIVE: To evaluate the relationship between nutrients intake in the first
      trimester of pregnancy and blood levels of lead and cadmium during the first and
      third trimesters of gestation. METHODS: A total of 381 pregnant women were
      enrolled. Blood lead and cadmium were measured using electrothermal atomic
      absorption spectrometry, and dietary intake was assessed using 24-h recall
      questionnaire. RESULTS: Lead levels in the first trimester were negatively
      correlated with cadmium levels in the two trimesters, and levels of both metals
      correlated positively in the third trimester. Zinc and calcium intakes were
      negatively associated with blood lead during third trimester. Thiamine and folic
      acid intakes were negatively and positively associated (respectively) with blood
      lead at third trimester with marginal significance. Fat, niacin, and vitamin B12
      intakes were significantly and positively associated with blood cadmium at first
      trimester. Folic acid and zinc intakes showed positive and marginally significant
      associations with blood cadmium without adjustments. At third trimester, blood
      cadmium was negatively associated to ascorbic acid intake, and positively
      associated with iron intake with a marginal significance. CONCLUSIONS: Possible
      acute and late effects of nutrients intake in blood lead and cadmium levels could
      be related with associations exclusively observed in the first and third
      trimester. This study represents the first exploration of relationships among a
      wide range of nutrients intake in the first trimester of pregnancy with blood
      lead and cadmium in first and third trimester of gestation. Further studies are
      required to confirm the findings mentioned herein.

PMID- 23559433
TI  - [Language development between the german preventive paediatric examinations at
      the age of 2 and 3 in children with and without language delay].
AB  - At the beginning the course of language acquisition has a high degree of
      variability and it is unclear so far, at what age language delay is of clinical
      relevance. The present study addresses the question whether language skills at
      the age of 2 years allow prognostic statements and whether children with language
      delay at this age, are to be considered as children of risk.Starting from birth
      announcements children of average (n=42), borderline (n=28) and below-average
      stage of language development (n=50) were recruited. The language skills were
      assessed at the age of 2 (25+0.6 months) and 3 years (37+0.6 months) using
      standardized language tests.The correlation between the global stage of language
      development at the age of 2 and 3 years was strong (rsp=0.78, p<0.001). At 3
      years of age one third of the former late talkers reached language abilities
      within the normal range (late bloomers), one third showed language difficulties
      and the last third met the criteria of specific language impairment. The risk for
      language difficulties was increased in these children to the 13-fold. Even the
      late bloomers scored significantly lower in the language test compared to the
      control children.From the third year of live language development is relatively
      stable, and language skills at the age of 2 allow a prediction of the stage of
      language development one year later. Late talkers are at high risk for persistent
      language difficulties. A general language screening at the age of 2 years would
      enable an early identification of children at risk and an early parent-based
      intervention. 

PMID- 23559434
TI  - Finding optimal finite field strengths allowing for a maximum of precision in the
      calculation of polarizabilities and hyperpolarizabilities.
AB  - The finite field method, widely used for the calculation of static dipole
      polarizabilities or the first and second hyperpolarizabilities of molecules and
      polymers, is thoroughly explored. The application of different field strengths
      and the impact on the precision of the calculations were investigated. Borders
      could be defined and characterized, establishing a range of feasible field
      strengths that guarantee reliable numerical results. The quality of different
      types of meshes to screen the feasible region is assessed. Extrapolation schemes
      are presented that reduce the truncation error and allow to increase the
      precision of finite field calculations by one to three orders of magnitude.

PMID- 23559435
TI  - Production of green biocellulose nanofibers by Gluconacetobacter xylinus through
      utilizing the renewable resources of agriculture residues.
AB  - The present study demonstrates the ability to produce green biocellulose
      nanofibers using the renewable resources of agriculture residues. Locally grown
      wheat straws (WS) were hydrolyzed under different conditions. Their hydrolysates
      were utilized to produce the nanofibers in separate hydrolysis fermentation
      process by Gluconacetobacter xylinus strain bacterium. Highest biocellulose
      production of ~10.6 g/L was achieved with samples that were enzymatically
      hydrolyzed. Moreover, acidic hydrolyzed WS produced up to 9.7 g/L, with total
      sugar concentrations in culture media of 43 g/L. Generally, enzymatic hydrolysis
      of WS resulted in more total sugar concentration than the acidic hydrolysis
      (i.e., 52.12 g/L), while water hydrolysis produced the least. This can be related
      to utilizing Xylanase in addition to Cellulase and Beta-glucosidase that helps to
      hydrolyse WS dry basis of cellulose and hemicelluloses. Sugar mixtures produced
      under all hydrolysis conditions were mainly composed of glucose and xylose with
      average percentages of 56 and 28 %, respectively. Acidic hydrolysis at higher
      acid concentration, as well as soaking WS in the acidic solution for longer time,
      improved the total sugar concentration in the culture media by 18 %. Conducting
      thermal treatment at more intense conditions of higher temperature or heating
      time improved the total sugar produced with acidic hydrolysis. These conditions,
      however, resulted in further production of furfural, which considerably affected
      bacterial cells proliferation. This resulted in lowest sugar consumption in the
      range of 62-64 % that affected final BC production.

PMID- 23559436
TI  - Molecule-induced peroxide homolysis.
AB  - The homolytic cleavage of peroxide bonds, leading to the formation of free
      radicals, plays an important role in the (spontaneous) oxidation of a wide
      variety of hydrocarbons in the presence of oxygen. Such aerobic oxidations can be
      desired (e.g. for industrially applied autoxidations) or undesired (e.g. food
      deterioration). In this contribution we provide experimental and computational
      evidence for a molecule-induced homolytic dissociation mechanism between alkyl
      peroxide and compounds featuring weakly bonded H atoms such as (di)unsaturated
      hydrocarbons.

PMID- 23559437
TI  - Comparison of temperature processing methods for monitoring focused ultrasound
      ablation in the brain.
AB  - PURPOSE: To investigate the performance of different reconstruction methods for
      monitoring temperature changes during transcranial magnetic resonance imaging
      (MRI)-guided focused ultrasound (MRgFUS). MATERIALS AND METHODS: Four different
      temperature reconstruction methods were compared in volunteers (without heating)
      and patients undergoing transcranial MRgFUS: single baseline subtraction,
      multibaseline subtraction, hybrid single baseline/referenceless reconstruction,
      and hybrid multibaseline/referenceless reconstruction. Absolute temperature error
      and temporal temperature uncertainty of the different reconstruction methods were
      analyzed and compared. RESULTS: Absolute temperature errors and temporal
      temperature uncertainty were highest with single baseline subtraction and lowest
      with hybrid multibaseline/referenceless reconstruction in all areas of the brain.
      Pulsation of the brain and susceptibility changes from tongue motion or
      swallowing caused substantial temperature errors when single or multibaseline
      subtraction was used, which were much reduced when the referenceless component
      was added to the reconstruction. CONCLUSION: Hybrid multibaseline/referenceless
      thermometry accurately measures temperature changes in the brain with fewer
      artifacts and errors due to motion than pure baseline subtraction methods.

PMID- 23559439
TI  - Reactions of pyridyl-functionalized, chelating lambda3-phosphinines in the
      coordination environment of Rh(III) and Ir(III).
AB  - Rh(III) and Ir(III) complexes based on the lambda(3)-P,N hybrid ligand 2-(2'
      pyridyl)-4,6-diphenylphosphinine (1) react selectively at the P=C double bond to
      chiral coordination compounds of the type [(1H?OH)Cp*MCl]Cl (2,3), which can be
      deprotonated with triethylamine to eliminate HCl. By using different bases, the
      pKa value of the P-OH group could be estimated. Whereas [(1H?O)Cp*IrCl] (4) is
      formed quantitatively upon treatment with NEt3, the corresponding rhodium
      compound [(1H?O)Cp*RhCl] (5) undergoes tautomerization upon formation of the
      lambda(5)sigma(4)-phosphinine rhodium(III) complex [(1?OH)Cp*RhCl] (6) as
      confirmed by single-crystal X-ray diffraction. Blocking the acidic P-OH
      functionality in 3 by introducing a P-OCH3 substituent leads directly to the
      lambda(5)sigma(4)-phosphinine iridium(III) complex (8) upon elimination of HCl.
      These new transformations in the coordination environment of Rh(III) and Ir(III)
      provide an easy and general access to new transition-metal complexes containing
      lambda(5)sigma(4)-phosphinine ligands.

PMID- 23559438
TI  - Cumulative incidence of cancer after solid organ transplantation.
AB  - BACKGROUND: Solid organ transplantation recipients have elevated cancer
      incidence. Estimates of absolute cancer risk after transplantation can inform
      prevention and screening. METHODS: The Transplant Cancer Match Study links the US
      transplantation registry with 14 state/regional cancer registries. The authors
      used nonparametric competing risk methods to estimate the cumulative incidence of
      cancer after transplantation for 2 periods (1987-1999 and 2000-2008). For
      recipients from 2000 to 2008, the 5-year cumulative incidence, stratified by
      organ, sex, and age at transplantation, was estimated for 6 preventable or screen
      detectable cancers. For comparison, the 5-year cumulative incidence was
      calculated for the same cancers in the general population at representative ages
      using Surveillance, Epidemiology, and End Results data. RESULTS: Among 164,156
      recipients, 8520 incident cancers were identified. The absolute cancer risk was
      slightly higher for recipients during the period from 2000 to 2008 than during
      the period from 1987 to 1999 (5-year cumulative incidence: 4.4% vs. 4.2%; P =
      .006); this difference arose from the decreasing risk of competing events (5-year
      cumulative incidence of death, graft failure, or retransplantation: 26.6% vs.
      31.9%; P < .001). From 2000 to 2008, the 5-year cumulative incidence of non
      Hodgkin lymphoma was highest at extremes of age, especially in thoracic organ
      recipients (ages 0-34 years: range, 1.74%-3.28%; aged >50 years; range, 0.36%
      2.22%). For recipients aged >50 years, the 5-year cumulative incidence was higher
      for colorectal cancer (range, 0.33%-1.94%) than for the general population at the
      recommended screening age (aged 50 years: range, 0.25%-0.33%). For recipients
      aged >50 years, the 5-year cumulative incidence was high for lung cancer among
      thoracic organ recipients (range, 1.16%-3.87%) and for kidney cancer among kidney
      recipients (range, 0.53%-0.84%). The 5-year cumulative incidence for prostate
      cancer and breast cancer was similar or lower in transplantation recipients than
      at the recommended ages of screening in the general population. CONCLUSIONS:
      Subgroups of transplantation recipients have a high absolute risk of some cancers
      and may benefit from targeted prevention or screening.

PMID- 23559440
TI  - Long-term acute care hospitals have low impact on medicare readmissions to short
      term acute care hospitals.
AB  - The relative contribution of long-term acute care hospital (LTACH) to short-term
      acute care hospital (STACH) Medicare patient readmissions is important because of
      the high acuity of LTACH patients. A retrospective cohort study was conducted to
      determine the magnitude of LTACH Medicare heart failure (HF) and pneumonia (PN)
      inpatient readmissions to STACHs within 30 days of LTACH admission and the
      relative contribution of LTACH patient readmissions to each STACH's total
      readmissions. Seventy-five for-profit LTACHs and their associated host or primary
      referral STACHs were studied. An average of 8% HF and 8% PN LTACH Medicare
      inpatients were readmitted to host or primary referral STACHs within 30 days of
      admission, representing 0.4% and 0.8% of the total number of HF and PN Medicare
      patients, respectively, readmitted to the STACHs in fiscal year 2010. The low
      rates of readmission from LTACHs to STACHs suggest an appropriate level of care
      for the LTACHs studied. 

PMID- 23559441
TI  - Identification of the degradation products of the steroid sulfatase inhibitor KW
      2581 in jet mill-micronized powder.
AB  - The novel steroid sulfatase inhibitor KW-2581 is poorly soluble in water, and jet
      milling was used in an attempt to increase its oral bioavailability.
      Unfortunately, however, the milled powder exhibited poorer qualities than the
      intact sample, including a lower level of crystallinity, higher water content,
      and increased decomposition rate. A comprehensive study of the jet milled sample
      was performed to identify the impurities and degradation mechanisms. The
      degradants were identified as the hydrolyzed and air-oxidized byproducts of KW
      2581. The radical propagation mechanism of the oxidation reactions associated
      with the degradation of KW-2581 was assumed to be mediated by water or metal
      catalysis. The inclusion of a drying process following the micronization step
      allowed for the decomposition mechanism to be successfully controlled in the
      subsequent storage of the jet mill-micronized KW-2581 drug substance.

PMID- 23559442
TI  - Complex visual hallucinations and attentional performance in eye disease and
      dementia: a test of the Perception and Attention Deficit model.
AB  - OBJECTIVE: This study aimed to test the prediction from the Perception and
      Attention Deficit model of complex visual hallucinations (CVH) that impairments
      in visual attention and perception are key risk factors for complex
      hallucinations in eye disease and dementia. METHODS: Two studies ran concurrently
      to investigate the relationship between CVH and impairments in perception
      (picture naming using the Graded Naming Test) and attention (Stroop task plus a
      novel Imagery task). The studies were in two populations-older patients with
      dementia (n = 28) and older people with eye disease (n = 50) with a shared
      control group (n = 37). The same methodology was used in both studies, and the
      North East Visual Hallucinations Inventory was used to identify CVH. RESULTS: A
      reliable relationship was found for older patients with dementia between impaired
      perceptual and attentional performance and CVH. A reliable relationship was not
      found in the population of people with eye disease. CONCLUSIONS: The results add
      to previous research that object perception and attentional deficits are
      associated with CVH in dementia, but that risk factors for CVH in eye disease are
      inconsistent, suggesting that dynamic rather than static impairments in
      attentional processes may be key in this population.

PMID- 23559443
TI  - Microevolution, migration, and the population structure of five Amerindian
      populations from Nicaragua and Costa Rica.
AB  - OBJECTIVE: This research examines the coevolution of languages and uniparental
      genetic marker (mitochondrial DNA [mtDNA] and nonrecombining Y-chromosome [NRY])
      variation within five Lower Central American (Rama, Chorotega, Maleku, Zapaton
      Huetar, and Abrojo-Guaymi) Amerindian groups. This pattern occurred since
      European contact. METHODS: We examined mtDNA sequence variation from the
      hypervariable region 1 (HVS-1) and NRY genetic variation using short tandem
      repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, and
      DYS439) and NRY haplogroups (Q1a3a, Q1a3*, C3b, R1b1b2, E1b1, G2a2, and I)
      identified through single-nucleotide polymorphisms. Phylogenetic analysis
      included multidimensional scaling (MDS), heterozygosity versus rii , and analysis
      of molecular variance (AMOVA). RESULTS: Eighteen mtDNA haplotypes were
      characterized in 131 participants with 94.6% of these assigned to the Amerindian
      mtDNA subclades, A2 and B2. The Amerindian NRY haplogroup, Q1a3a, was present in
      all five groups and ranged from 85% (Zapaton-Huetar) to 35% (Chorotega). Four
      populations (Rama, Chorotega, Zapaton-Huetar, and Abrojo-Guaymi) were also
      characterized by the presence of NRY haplogroup R1b1b2 indicative of western
      European admixture. Seventy NRY STR haplotypes were identified of which 69 (97%)
      were population specific. MDS plots demonstrated genetic similarities between
      Mesoamericans and northern Chibchan Amerindian populations, absent in mtDNA
      analyses, which is further supported by heterozygosity versus rii results.
      CONCLUSIONS: We conclude that although these linguistically related populations
      in geographic proximity demonstrate a high degree of paternal genetic
      differentiation, recent demographic events have dramatically altered the paternal
      genetic structure of the regions Amerindian populations.

PMID- 23559444
TI  - Porous poly(epsilon-caprolactone) scaffolds for load-bearing tissue regeneration:
      solventless fabrication and characterization.
AB  - Three-dimensional interconnected porous poly(epsilon-caprolactone) scaffolds have
      been prepared by a novel solventless scaffold fabrication approach combining
      cryomilling and compression molding/porogen leaching techniques. This study
      investigated the effects of processing parameters on scaffold morphology and
      properties for tissue regeneration. Specifically, the effects of molding
      temperature, cryomilling time, and porogen mix were examined. Fifty percentage of
      porous scaffolds were fabricated with a range of properties: mean pore size from
      ~40 to 125 MUm, water uptake from ~50 to 86%, compressive modulus from ~45 to 84
      MPa, and compressive strength at 10% strain from ~3 to 4 MPa. Addition of 60 wt %
      NaCl salt resulted in a ~50% increase in porosity in multimodal pore-size
      structures that depended on the method of NaCl addition. Water uptake ranged from
      ~61 to 197%, compressive modulus from ~4 to 8.6 MPa, and compressive strength at
      10% strain from ~0.36 to 0.40 MPa. Results suggest that this approach provides a
      controllable strategy for the design and fabrication of 3D interconnected porous
      biodegradable scaffolds for load-bearing tissue regeneration.

PMID- 23559445
TI  - [Legal regulation of coercion in psychiatry--a task for the professional
      association?].

PMID- 23559446
TI  - [Video surveillance in psychiatric hospitals--pro & contra].

PMID- 23559448
TI  - [Reports from the Federal Conference of German Psychiatry and Psychotherapy
      Clinics].

PMID- 23559449
TI  - Discordant noninvasive prenatal testing results in a patient subsequently
      diagnosed with metastatic disease.

PMID- 23559450
TI  - Gastric cancer prevention by demethylation.
AB  - Niwa and colleagues report in this issue that treatment with the DNA
      demethylation agent 5-aza-2'-deoxycytidine decreases the incidence of gastric
      cancers in an animal model of Helicobacter pylori-promoted gastric cancer. This
      provocative study underscores the importance of changes in DNA methylation that
      contribute to the origin of inflammation-related cancers. The findings also raise
      the exciting possibility of cancer prevention by altering DNA methylation events
      early during tumorigenesis.

PMID- 23559451
TI  - Ginger: is it ready for prime time?
AB  - On the basis of substantial preclinical data showing the preventive efficacy of
      ginger and its constituents in vitro and in animal models, as well as a phase I
      pilot trial indicating that ginger extract is well tolerated in humans,
      Citronberg and colleagues conducted a pilot trial of ginger extract (2 g/day for
      28 days) on biomarkers of cell proliferation [human telomerase reverse
      transcriptase (hTERT), MIB-1], differentiation (p21waf1/cip1), and apoptosis
      (Bax, Bcl-2) in colonic mucosa from individuals at high-risk for colorectal
      cancer. Results from the trial suggest that ginger may reduce proliferation in
      normal-appearing colorectal epithelium and increase apoptosis relative to
      proliferation, especially in the differentiation zone of colon crypts. The
      authors suggest that these results support a larger study to confirm the pilot
      data. Before proceeding with a larger trial, however, it seems prudent to confirm
      ginger as a chemopreventive for colorectal cancer in animals, particularly when
      tested in postinitiation protocols and to identify reliable molecular biomarkers
      of effect that could be evaluated in clinical trials. Pharmacokinetic studies to
      examine the distribution and localization of ginger compounds and metabolites in
      the differentiation and proliferative zones of colonic crypts in animals and
      humans would also be informative. Finally, because the effects of ginger on
      normal colonic mucosa seem minimal, consideration should be given to the conduct
      of future trials in humans with premalignant colorectal disease.

PMID- 23559452
TI  - Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA
      demethylating agent.
AB  - Suppression of aberrant DNA methylation is a novel approach to cancer prevention,
      but, so far, the efficacy of the strategy has not been evaluated in cancers
      associated with chronic inflammation. Gastric cancers induced by Helicobacter
      pylori infection are known to involve aberrant DNA methylation and associated
      with severe chronic inflammation in their early stages. Here, we aimed to clarify
      whether suppression of aberrant DNA methylation can prevent H. pylori-induced
      gastric cancers using a Mongolian gerbil model. Administration of a DNA
      demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), to gerbils (0.125 mg/kg
      for 50-55 weeks) decreased the incidence of gastric cancers induced by H. pylori
      infection and N-methyl-N-nitrosourea (MNU) treatment from 55.2% to 23.3% (P <
      0.05). In gastric epithelial cells, DNA methylation levels of six CpG islands
      (HE6, HG2, SB1, SB5, SF12, and SH6) decreased to 46% to 68% (P < 0.05) of gerbils
      without 5-aza-dC treatment. Also, the global DNA methylation level decreased from
      83.0% +/- 4.5% to 80.3% +/- 4.4% (mean +/- SD) by 5-aza-dC treatment (P < 0.05).
      By 5-aza-dC treatment, Il1b and Nos2 were downregulated (42% and 58% of gerbils
      without, respectively) but Tnf was upregulated (187%), suggesting that 5-aza-dC
      treatment induced dysregulation of inflammatory responses. No obvious adverse
      effect of 5-aza-dC treatment was observed, besides testicular atrophy. These
      results showed that 5-aza-dC treatment can prevent H. pylori-induced gastric
      cancers and suggested that removal of induced DNA methylation and/or suppression
      of DNA methylation induction can become a target for prevention of chronic
      inflammation-associated cancers.

PMID- 23559453
TI  - Quantitative multiparametric MRI of ovarian cancer.
AB  - PURPOSE: To identify parameters associated with ovarian malignancy using
      multiparametric quantitative magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: After Institutional Review Board (IRB) approval, women with ovarian
      masses underwent preoperative imaging with 3 T MRI. Dynamic contrast-enhanced
      (DCE)-MRI with pharmacokinetic modeling, quantitative T2 mapping, and diffusion
      weighted imaging with quantitative mapping of the water diffusion parameters were
      performed. Ovarian masses had one or more discreet regions of interest,
      categorized as cystic or solid, and histologically diagnosed as benign or
      malignant. Mean region of interest (ROI) values were compared between benign and
      malignant masses using generalized estimating equations. In addition, we compared
      classification accuracy for the mean ROI value to a combination of histogram
      characteristics (standard deviation, skewness, and kurtosis) from T2 map ROIs
      using logistic regression and ROC curve. The significance level was P = 0.05.
      RESULTS: Several DCE-MRI parameters differentiated solid benign from malignant
      masses. Toft's rate constant (kep ) was significantly higher in malignant masses
      (P < 0.001), as well as quantitative T2 values (P = 0.003), and signal intensity
      on T2 weighted imaging (P = 0.008). A linear combination of the mean, standard
      deviation, skewness, and kurtosis of T2 within solid regions (area under the
      curve [AUC] 0.90) provided better classification accuracy than the mean of T2
      alone (AUC 0.81). CONCLUSION: Quantitative parameters from DCE-MRI and T2 mapping
      can differentiate benign from malignant ovarian masses.

PMID- 23559455
TI  - Highly enantioselective aldol reactions between acetaldehyde and activated
      acyclic ketones catalyzed by chiral primary amines.
AB  - Highly enantioselective cross-aldol reactions between acetaldehyde and activated
      acyclic ketones are reported for the first time. Various acyclic ketones, such as
      saturated and unsaturated keto esters, reacted with acetaldehyde in the presence
      of a chiral primary amine and a Bronsted acid to afford optically enriched
      tertiary alcohols in good yields and with excellent enantioselectivities.
      Trifluoromethyl ketones were tolerable under the reaction conditions, thereby
      affording the trifluoromethyl carbinol in good-to-excellent yields and
      enantioselectivities. Structural modification of the chiral amines from the same
      chiral source switched the stereoselectivity of the products. The utility of
      aldol chemistry was demonstrated in the brief synthesis of functionally enriched
      delta-lactones. Theoretical calculations on the transition-state structure
      indicated that the protonated tertiary amine could effectively activate the
      carbonyl group of a keto ester to promote the addition process through hydrogen
      bonding interaction and, simultaneously, provide an appropriate attacking pattern
      for the approach of the keto ester to the enamine, which is formed from
      acetaldehyde and the chiral catalyst, on a particular face, resulting in high
      enantioselectivity.

PMID- 23559454
TI  - Preliminary investigation of the effect of pulse rate on judgments of swallowing
      impairment and treatment recommendations.
AB  - Reducing fluoroscopic pulse rate, a method used to reduce radiation exposure from
      modified barium swallow studies (MBSSs), decreases the number of images available
      from which to judge swallowing impairment. It is necessary to understand the
      impact of pulse rate reduction on judgments of swallowing impairment and,
      consequentially, treatment recommendations. This preliminary study explored
      differences in standardized MBSS measurements [Modified Barium Swallow Impairment
      Profile (MBSImPTM(c)) and Penetration Aspiration Scale (PAS) Scores] between two
      pulse rates: 30 and simulated 15 pulses per second (pps). Two reliable speech
      language pathologists (SLPs) scored all five MBSSs. Five SLPs reported treatment
      recommendations based on those scores. Differences in judgments of swallowing
      impairment were found between 30 and simulated 15 pps in all five MBSSs. These
      differences were in six physiological swallowing components: initiation of
      pharyngeal swallow, anterior hyoid excursion, epiglottic movement, pharyngeal
      contraction, pharyngeal-esophageal segment opening, and tongue base retraction.
      Differences in treatment recommendations were found between 30 and simulated 15
      pps in all five MBSSs. These findings suggest that there are differences in both
      judgment of swallowing impairment and treatment recommendations when pulse rates
      are reduced from 30 to 15 pps to minimize radiation exposure. 

PMID- 23559456
TI  - Oseltamivir phosphate-amberlite(TM) IRP 64 ionic complex for taste masking:
      preparation and chemometric evaluation.
AB  - The objective of the present work was to evaluate and characterize a pediatric
      friendly formulation of a bitter tasting drug, oseltamivir phosphate (drug).
      Amberlite IRP64 (resin) was used to make ionic complexes for masking its
      bitterness. Complexes of four drug-to-resin ratios, 1:1, 1:2, 1:4, and 1:6 (w/w),
      were prepared and characterized. At buccal pH of 6.8, drug-resin complexes of
      1:1, 1:2, 1:4, and 1:6 ratios released 42.13%, 23.26%, 4.13%, and 14.94%,
      respectively, of loaded drug after 20 s. However, at stomach pH of 1.2 (0.1 N
      HCl), 61.96%, 70.18%, 85.88%, and 91.42% of drug was released from the same
      complexes in 6 min. Near-infrared (NIR) chemical imaging of the complexes showed
      homogeneous distribution of drug in the resin. Chemometric partial least squares
      model using NIR data of the drug showed a high correlation between calibration
      and predicted data (R(2) > 0.998). Overall, these results indicated the complex
      formation between drug and resin. The pH dependence of drug release from these
      complexes could minimize drug release in the mouth, whereas immediately releasing
      it in the stomach. Electronic tongue used to evaluate taste indicated that
      conductivity taste signals were different from control, suggesting taste masking
      of the drug.

PMID- 23559457
TI  - The associations of SES, obesity, sport activity, and perceived neighborhood
      environments: is there a model of environmental injustice penalizing Portuguese
      children?
AB  - OBJECTIVES: This study analyses the associations between children's obesity,
      sports activity (SA), and perceived environmental characteristics with the
      children's SES. METHODS: A sample of 1,885 Portuguese children, aged 3-10 years,
      living in Coimbra, Portugal, was observed. Weight and height were measured and
      obesity was defined by age-and sex-specific, BMI cut-off points. Questionnaires
      included variables on SA levels, SES and parental neighborhood perceptions were
      done. A CATPCA was performed and two neighborhood dimensions were achieved. The
      independent associations of SES with obesity, SA and perceived neighborhood
      dimensions was analyzed using ordered logistic regressions. RESULTS: Children of
      low [odds ratio (OR) = 1.76; confidence interval (CI) = 1.25-1.99] and medium SES
      (OR = 1.57; CI = 1.34-2.33) were more likely to be obese than their high-SES
      peers, less likely to participate in SA (low SES OR = 0.177; CI = 0.12-0.26;
      medium SES OR = 0.357; CI = 0.24-0.53), and their parents were less likely to
      have positive perceptions of their built environment (low SES OR = 0.516; CI =
      0.38-0.70; medium SES OR = 0.565; CI = 0.37-0.86). CONCLUSIONS: Obesity increases
      and SA decreases among children with the lowest SES and these living in
      neighborhoods with higher perceived risk. This finding suggests a model of
      environmental injustice, whereby differential access to the neighborhood's
      resources overlaps with familial socioeconomic disadvantage.

PMID- 23559458
TI  - Re-examining ethnic differences in concerns, knowledge, and beliefs about
      Alzheimer's disease: results from a national sample.
AB  - OBJECTIVE: This study aims to evaluate ethnic group differences in concerns,
      knowledge, and beliefs about Alzheimer's disease (AD) in three ethnic groups of
      older adults (White, Latino, and Black). METHODS: The Health and Retirement Study
      is a US national representative study of older adults over the age of 50 years
      and their spouse of any age. The study is based on the 2010 wave. RESULTS:
      Analysis is based on data from 939 White, 120 Latino, and 171 Black respondents
      who completed a special module about AD concerns, knowledge, and beliefs. There
      were significant ethnic differences on 7 of 13 items. However, after the
      adjustment for education, gender, age, having a family member with AD, depressive
      symptoms, and medical comorbidity, only four items showed significant ethnic
      group differences; relative to White respondents, Black respondents were less
      likely to report that having a parent or a sibling with AD increases the chance
      of developing AD and that genetics was an important risk for AD. In addition,
      relative to White respondents, both Black and Latino respondents were more likely
      to perceive stress as a potential risk for AD. Latino respondents were less
      likely to perceive mental activity as a protective factor. CONCLUSIONS: The study
      found limited ethnic group differences, with most items showing a similar pattern
      across groups. Nevertheless, the nature of the ethnic group differences found
      might be associated with a differential pattern of health service use.

PMID- 23559459
TI  - Effect and clinical implications of the low-energy diode laser on bone cell
      proliferation.
AB  - Laser is a simple, noninvasive technique that has proven useful for treating
      damaged tissue. However, its effects on bone regeneration and the mechanisms
      involved are poorly understood. The objective of this study was to evaluate the
      effects on MG-63 cell proliferation of application of a pulsed diode laser
      (Ezlase) of 940 nm at low energy levels. After 24 hr of culture, osteoblasts
      underwent pulsed laser radiation at 0.5, 1, 1.5, and 2 W and fluences of 1-5 J. A
      control group was not irradiated. After the treatment, cells were incubated for
      24 hr, and cell proliferation was analyzed using a spectrophotometric measure of
      cell respiration (MTT assay). Results were expressed as percentage proliferation
      versus controls. At 24-hr culture, cell proliferation was increased in laser
      treated cells at intensities of 0.5, 1, and 1.5 W/cm(2) versus controls; the
      energy density was positively correlated with cell growth, which reached a peak
      at 3 J and decreased at higher fluences. The use of pulsed low-level laser with
      low-energy density range thus appears to exert a biostimulatory effect on bone
      tissue. Although the data on cell proliferation are robust, in-depth
      investigation is required into the effect of these irradiation doses on other
      cell parameters. The present findings demonstrate that laser therapy could be
      highly useful in tissue regeneration in different clinical settings, including
      nursing, physical therapy, dentistry, and traumatology.

PMID- 23559460
TI  - Dynamic competitive adsorption of bone-related proteins on calcium phosphate
      ceramic particles with different phase composition and microstructure.
AB  - The biocompatibility and bioactivity of biomaterials used for hard tissue repair
      are closely related to their adsorption capacities for bone-related proteins. In
      the present study, three types of calcium phosphate (CaP) ceramic particles with
      different phase composition or microstructure were fabricated, and their protein
      adsorption abilities were investigated by a self-made device under the simulated
      dynamic physiological circumstance. The results of X-ray diffraction, field
      emission scanning electron microscopy, mercury penetration test, and nitrogen
      sorption test showed that the irregular hydroxyapatite (HA) ceramic particles
      obtained by conventional drying and sintering (named as HA-C) had fewer
      micropores and lower specific surface area (SSA) than did the spherical HA or
      biphasic calcium phosphate (BCP) ceramic particles made by spray drying and
      sintering (named as HA-S and BCP-S, respectively). The dynamic protein adsorption
      study proved that both the phase composition and microstructure of CaP ceramic
      particles affected their adsorption capacities for those bone-related proteins.
      The spherical HA-S and BCP-S particles with abundant micropores and high SSA
      showed higher adsorption of serum proteins, including fibronectin and
      vitronectin, than the irregular HA-C did. On the other hand, in spite of the
      relatively high concentration of bovine serum albumin (BSA) in the binary bone
      morphogenetic protein 2 (BMP-2)/BSA solution, BMP-2 adsorption on the three CaP
      ceramic particles increased with the increase in its initial concentration.
      Similarly, HA-S and BCP-S particles had a larger amount of the adsorbed BMP-2 per
      gram solid than HA-C did. Therefore, it could be believed that the difference of
      various CaP ceramics in the phase composition and microporous structure would
      affect their binding capacity for those bone-related proteins and thus lead to
      their difference in osteoinduction.

PMID- 23559461
TI  - No evidence of viral coinfection in cerebrospinal fluid from patients with
      community-acquired bacterial meningitis.

PMID- 23559462
TI  - A norovirus outbreak related to contaminated surfaces.
AB  - We investigated an outbreak of norovirus infection affecting 12 of 16 auto
      dealership employees (75%) subsequent to a staff meeting. Take-out sandwiches
      initially seemed the likely source, but a cohort study found no association
      between illness and food consumption. Employees reported seeing a toddler with
      diarrhea in a dealership restroom shortly before the luncheon. Indistinguishable
      norovirus was isolated from employees and the child (genotype GII6.C) and from a
      diaper-changing station in the restroom (genogroup GII). Counterintuitively, this
      point-source outbreak following a meal was caused by environmental exposures, not
      food. Environmental exposures should be considered even in routine outbreak
      investigations.

PMID- 23559463
TI  - Perinatal exposure of patas monkeys to antiretroviral nucleoside reverse
      transcriptase inhibitors induces genotoxicity persistent for up to 3 years of
      age.
AB  - BACKGROUND: Erythrocebus patas (patas) monkeys were used to model antiretroviral
      (ARV) drug in human immunodeficiency virus type 1-infected pregnant women.
      METHODS: Pregnant patas dams were given human-equivalent doses of ARVs daily
      during 50% of gestation. Mesenchymal cells, cultured from bone marrow of patas
      offspring obtained at birth and at 1 and 3 years of age, were examined for
      genotoxicity, including centrosomal amplification, micronuclei, and micronuclei
      containing whole chromosomes. RESULTS: Compared with controls, statistically
      significant increases (P < .05) in centrosomal amplification, micronuclei, and
      micronuclei containing whole chromosomes were found in mesenchymal cells from
      most groups of offspring at the 3 time points. CONCLUSIONS: Transplacental
      nucleoside reverse-transcriptase inhibitor exposures induced fetal genotoxicity
      that was persistent for 3 years.

PMID- 23559464
TI  - Genotoxic signature in cord blood cells of newborns exposed in utero to a
      Zidovudine-based antiretroviral combination.
AB  - BACKGROUND: The genotoxicity of zidovudine has been established in experimental
      models. The objective of the study was to identify genotoxicity markers in cord
      blood cells from newborns exposed in utero to antiretroviral (ARV) combinations
      containing zidovudine. METHODS: Cells were investigated by karyotyping and gene
      expression analysis of the CD34(+) hematopoietic stem/progenitor cell (HPC)
      compartment. RESULTS: Karyotyping of the cord blood cells from 15 ARV-exposed
      newborns and 12 controls revealed a higher proportion of aneuploid cells in the
      exposed group (median, 18.8% [interquartile range, 10.0%-26.7%] vs 6.6%
      [interquartile range, 3.1%-11.7%]; P < .001). All chromosomes were involved, with
      a random distribution of these alterations. Gene expression profiling of CD34(+)
      HPCs from 7 ARV-exposed and 6 control newborns revealed that >300 genes were
      significantly upregulated or downregulated by at least 1.5-fold in the exposed
      group (P < .05 for all comparisons). Significant alterations of genes involved in
      cell cycle control, mitotic checkpoints, and DNA repair were identified. Although
      this study does not allow discrimination between the roles of each of the 3
      drugs, both cytogenetic and transcriptional findings are similar to those in
      cellular experiments that used zidovudine alone. CONCLUSIONS: The cord blood
      cells, including hematopoietic stem cells, from newborns exposed in utero to a
      zidovudine-based ARV combination present cytogenetic and transcriptional
      abnormalities compatible with DNA damage.

PMID- 23559465
TI  - Expansion and evolution of Streptococcus pneumoniae serotype 19A ST320 clone as
      compared to its ancestral clone, Taiwan19F-14 (ST236).
AB  - BACKGROUND: The Streptococcus pneumoniae serotype 19A sequence type (ST) 320
      clone, derived from an international Taiwan(19F)-14 (ST236) clone, has become
      prevalent in many countries. METHODS: The dynamics of invasive pneumococcal
      disease (IPD) were determined using the database of the National Notifiable
      Disease Surveillance System in Taiwan. The virulence of 19A ST320 and Taiwan(19F)
      14 (ST236) were assessed in mice. By constructing an isogenic serotype 19F
      variant of the 19A ST320 strain (19F ST320), we analyzed the role of capsular
      type and genetic background on the difference in virulence between 19A ST320 and
      Taiwan(19F)-14 (ST236). RESULTS: Between 2008 and 2011, IPD due to serotype 19A
      increased from 2.1 to 10.2 cases per 100 000 population (P < .001); IPD due to
      any serotype also significantly increased (P = .01). Most serotype 19A isolates
      belonged to ST320. Using competition experiments in a murine model of
      colonization, we demonstrated that 19A ST320 outcompeted Taiwan(19F)-14 (ST236;
      competitive index, 20.3; P = .001). 19F ST320 was 2-fold less competitive than
      the 19A ST320 parent (competitive index, 0.47; P = .04) but remained 14-fold more
      competitive than Taiwan(19F)-14 (ST236; competitive index, 14.7; P < .001).
      CONCLUSIONS: Genetic evolution of pneumococcal clones from Taiwan(19F)-14 (ST236)
      to 19A ST320 has made this pneumococcus better able to colonize of the
      nasopharynx. This evolution reflects not only a switch in capsular serotype but
      also changes in other loci.

PMID- 23559467
TI  - Fat fraction bias correction using T1 estimates and flip angle mapping.
AB  - PURPOSE: To develop a new method of reducing T1 bias in proton density fat
      fraction (PDFF) measured with iterative decomposition of water and fat with echo
      asymmetry and least-squares estimation (IDEAL). MATERIALS AND METHODS: PDFF maps
      reconstructed from high flip angle IDEAL measurements were simulated and acquired
      from phantoms and volunteer L4 vertebrae. T1 bias was corrected using a priori T1
      values for water and fat, both with and without flip angle correction. Signal-to
      noise ratio (SNR) maps were used to measure precision of the reconstructed PDFF
      maps. PDFF measurements acquired using small flip angles were then compared to
      both sets of corrected large flip angle measurements for accuracy and precision.
      RESULTS: Simulations show similar results in PDFF error between small flip angle
      measurements and corrected large flip angle measurements as long as T1 estimates
      were within one standard deviation from the true value. Compared to low flip
      angle measurements, phantom and in vivo measurements demonstrate better precision
      and accuracy in PDFF measurements if images were acquired at a high flip angle,
      with T1 bias corrected using T1 estimates and flip angle mapping. CONCLUSION: T1
      bias correction of large flip angle acquisitions using estimated T1 values with
      flip angle mapping yields fat fraction measurements of similar accuracy and
      superior precision compared to low flip angle acquisitions.

PMID- 23559468
TI  - Transition-metal-free one-pot synthesis of biaryls from Grignard reagents and
      substituted cyclohexanones.
AB  - A new strategy for the construction of biaryls by a transition-metal-free process
      is presented. A sequence of a Grignard reaction, dehydration, and oxidative
      aromatization affords the desired products in a one-pot fashion.

PMID- 23559466
TI  - Association of functional impairment with inflammation and immune activation in
      HIV type 1-infected adults receiving effective antiretroviral therapy.
AB  - BACKGROUND: The relationships of inflammation, immune activation, and
      immunosenescence markers with functional impairment in aging human
      immunodeficiency virus type 1 (HIV-1)-infected persons are unknown. METHODS: HIV
      infected persons who were aged 45-65 years, had a plasma HIV-1 RNA load of <48
      copies/mL, and were receiving antiretroviral therapy underwent standardized
      functional testing. In a nested case-control analysis, low-functioning cases were
      matched (1:1-2) by age, sex, and HIV-1 diagnosis date to high-functioning
      controls. Markers of inflammation, T-cell activation, microbial translocation,
      immunosenescence, and immune recovery were used to estimate functional status in
      conditional logistic regression. Primary analyses were adjusted for CD4(+) T-cell
      count, smoking, and hepatitis. RESULTS: Thirty-one low-functioning cases were
      compared to 49 high-functioning controls. After statistical adjustment, lower
      proportions of CD4(+) T cells and higher proportion of CD8(+) T cells, higher
      CD38/HLA-DR expression on CD8(+) T cells, and higher interleukin-6 were
      associated with a significantly greater odds of low functional status (odds
      ratio, >= 1.1 for all analyses; P <= .03). Other inflammatory, senescence, and
      microbial translocation markers were not significantly different (P >= .11 for
      all analyses) between low-functioning and high-functioning groups. CONCLUSIONS:
      Functional impairment during successful antiretroviral therapy was associated
      with higher CD8(+) T-cell activation and interleukin 6 levels. Interventions to
      decrease immune activation and inflammation should be evaluated for their effects
      on physical function and frailty.

PMID- 23559469
TI  - Changes in maternal secretory immunoglobulin a levels in human milk during 12
      weeks after parturition.
AB  - BACKGROUND: Immune factors in human milk change in concentration after delivery.
      However, this concentration change during the early postpartum period has not yet
      been investigated in detail. METHODS: We measured Secretory IgA (SIgA) levels in
      the human milk of 91 postpartum mothers (after vaginal delivery) by using an
      enzyme immunoassay, in postpartum day 3, and weeks 1, 2, 3, 4, 8, and 12.
      RESULTS: The SIgA concentration gradually declined over the 12-week period, with
      the highest level recorded in day 3. At week 4, the SIgA levels decreased to half
      the initial levels. Although the difference in concentration from one week to the
      next was remarkable, the decrease in concentration was rapid in the first 4 weeks
      but gradual from week 4 to week 12. CONCLUSIONS: The SIgA levels gradually
      decreased up to week 12. However, the concentration of SIgA in breast milk did
      not change constantly. It changed relatively rapid until 4 weeks after
      childbirth, and because the concentration from the third day to the eighth week
      became 50%, it was understood that the change was temporal.

PMID- 23559470
TI  - Characterization of a novel active release coating to prevent biofilm implant
      related infections.
AB  - Biofilm implant-related infections cost the US healthcare system billions of
      dollars each year. For several decades, device coatings have been developed that
      actively release antimicrobial compounds in an attempt to prevent these
      infections from developing. To date, few coatings have been put into clinical
      use. These have shown limited to no efficacy in clinical trials. Recent data have
      shown the in vitro and in vivo efficacy of a novel active release coating that
      may address the limitations of coatings that are used clinically. In this study,
      the novel active release coating was characterized to gain an understanding of
      the effects of combining an antimicrobial additive, cationic steroid
      antimicrobial-13 (CSA-13), to a medical grade polydimethylsiloxane (PDMS)
      material. Results indicated that the addition of CSA-13 did influence the
      physical properties of the PDMS, but not with adverse effects to the desired
      material properties. Furthermore, there was no indication of chemical reactivity.
      It was shown that CSA-13 was uniformly dispersed as small particles throughout
      the PDMS matrix. These particles were able to dissolve and elute out of the PDMS
      within a 30-day period. The results of this work suggested that the PDMS with CSA
      13 was thermally, chemically and physically stable when used as a device coating
      to treat local infection and/or prevent biofilm implant-related infections from
      developing.

PMID- 23559475
TI  - Late gadolinium enhancement in the assessment of the infarcted mouse heart: a
      longitudinal comparison with manganese-enhanced MRI.
AB  - PURPOSE: To evaluate late gadolinium-enhanced (LGE) assessment of infarct size, a
      comparison with manganese-enhanced magnetic resonance imaging (MEMRI), and
      histology was performed in a permanent infarction model in the mouse at the acute
      and chronic stage. MATERIALS AND METHODS: In a paired fashion at the acute and
      chronic stage after infarction (3-4 days and 21 days, respectively), LGE and
      MEMRI was performed using a self-gated fast low flip angle shot (FLASH). Infarct
      size was evaluated as the enhanced area relative to the complete myocardial wall
      area in a mid-ventricular slice. Paired comparisons were made between contrast
      agents and between timepoints, as well as to histology. RESULTS: At the acute
      stage, LGE delineated a larger infarct size as compared to both MEMRI and
      histology. Infarct size from LGE decreased from the acute to chronic stage, a
      temporal development not seen with MEMRI. At the chronic stage, no significant
      differences in infarct size were found between the methods. CONCLUSION: This
      study indicates an overenhancement of infarct size when using LGE, supported by
      an initial overestimation at the acute stage and a temporal decrease in infarct
      size from the acute to chronic stage, as compared to infarct size from MEMRI.

PMID- 23559476
TI  - Identification and characterization of a linearized B-cell epitope on the pr
      protein of dengue virus.
AB  - The four serotypes of dengue virus (DENV) represent one of the major mosquito
      borne pathogens globally; so far no vaccine or specific antiviral is available.
      During virion maturation, the pr protein is cleaved from its precursor form the
      prM protein on the surface of immature DENV by host protease. Recent findings
      have demonstrated that the pr protein not only played critical roles in virion
      assembly and maturation, but was also involved in antibody-dependent enhancement
      of DENV infection. However, the B-cell epitopes on the pr protein of DENV have
      not been well characterized. In this study, a set of 11 partially overlapping
      peptides spanning the entire pr protein of DENV-2 were fused with glutathione S
      transferase and expressed in Escherichia coli. ELISA screening with murine
      hyperimmune antiserum against immature DENV identified the P8 peptide
      (57KQNEPEDIDCWCNST71) in the pr protein as the major immunodominant epitope. Fine
      mapping by truncated protein assays confirmed the 8-e peptide 57KQNEPEDI64 was
      the smallest unit capable of antibody binding. Importantly, the 8-e epitope
      reacted with sera from dengue fever patients. Site-directed mutagenesis revealed
      the asparagine residue at position 59 was important for epitope recognition. The
      8-e epitope coincided well with the B-cell epitopes predicted by Immune Epitope
      Database analysis, and 3D structural modelling mapped the 8-e peptide on the
      surface of prM-E heterodimers. Overall, our findings characterized a linearized B
      cell epitope on the pr protein of DENV, which will help to understand the life
      cycle of DENV and pathogenesis of dengue infections in human.

PMID- 23559477
TI  - An infectious recombinant foot-and-mouth disease virus expressing a fluorescent
      marker protein.
AB  - Foot-and-mouth disease virus (FMDV) is one of the most extensively studied animal
      pathogens because it remains a major threat to livestock economies worldwide.
      However, the dynamics of FMDV infection are still poorly understood. The
      application of reverse genetics provides the opportunity to generate molecular
      tools to further dissect the FMDV life cycle. Here, we have used reverse genetics
      to determine the capsid packaging limitations for a selected insertion site in
      the FMDV genome. We show that exogenous RNA up to a defined length can be stably
      introduced into the FMDV genome, whereas larger insertions are excised by
      recombination events. This led us to construct a recombinant FMDV expressing the
      fluorescent marker protein, termed iLOV. Characterization of infectious iLOV-FMDV
      showed the virus has a plaque morphology and rate of growth similar to the
      parental virus. In addition, we show that cells infected with iLOV-FMDV are
      easily differentiated by flow cytometry using the inherent fluorescence of iLOV
      and that cells infected with iLOV-FMDV can be monitored in real-time with
      fluorescence microscopy. iLOV-FMDV therefore offers a unique tool to characterize
      FMDV infection in vitro, and its applications for in vivo studies are discussed.

PMID- 23559478
TI  - Knockdown of piRNA pathway proteins results in enhanced Semliki Forest virus
      production in mosquito cells.
AB  - The exogenous siRNA pathway is important in restricting arbovirus infection in
      mosquitoes. Less is known about the role of the PIWI-interacting RNA pathway, or
      piRNA pathway, in antiviral responses. Viral piRNA-like molecules have recently
      been described following infection of mosquitoes and derived cell lines with
      several arboviruses. The piRNA pathway has thus been suggested to function as an
      additional small RNA-mediated antiviral response to the known infection-induced
      siRNA response. Here we show that piRNA-like molecules are produced following
      infection with the naturally mosquito-borne Semliki Forest virus in mosquito cell
      lines. We show that knockdown of piRNA pathway proteins enhances the replication
      of this arbovirus and defines the contribution of piRNA pathway effectors, thus
      characterizing the antiviral properties of the piRNA pathway. In conclusion,
      arbovirus infection can trigger the piRNA pathway in mosquito cells, and
      knockdown of piRNA proteins enhances virus production.

PMID- 23559479
TI  - Genetic characterization of a novel picornavirus in turkeys (Meleagris gallopavo)
      distinct from turkey galliviruses and megriviruses and distantly related to the
      members of the genus Avihepatovirus.
AB  - This study reports the metagenomic detection and complete genome characterization
      of a novel turkey picornavirus from faecal samples of healthy (1/3) and affected
      (6/8) commercial turkeys with enteric and/or stunting syndrome in Hungary. The
      virus was detected at seven of the eight farms examined. The turkey/M176
      TuASV/2011/HUN genome (KC465954) was genetically different from the currently
      known picornaviruses of turkey origin (megriviruses and galliviruses), and showed
      distant phylogenetic relationship and common genomic features (e.g. uncleaved VP0
      and three predicted and unrelated 2A polypeptides) to duck hepatitis A virus
      (DHAV) of the genus Avihepatovirus. The complete genome analysis revealed
      multiple distinct genome features like the presence of two in-tandem aphthovirus
      2A-like sequence repeats with DxExNPG/P 'ribosome-skipping' sites (76 %, 23/30
      amino acids identical), with the first aphthovirus 2A-like sequence being located
      at the end of the VP1 capsid protein (VP1/2A1 'ribosome-skipping' site). The
      phylogenetic analyses, low sequence identity (33, 32 and 36 % amino acid identity
      in P1, P2 and P3 regions) to DHAV, and the type II-like internal ribosome entry
      site suggests that this turkey picornavirus is related to, but distinct from the
      genus Avihepatovirus and it could be the founding member of a novel
      Avihepatovirus sister-clade genus. This is the third, taxonomically highly
      distinct picornavirus clade identified from turkeys exhibiting varied symptoms.

PMID- 23559480
TI  - RAGE inhibits human respiratory syncytial virus syncytium formation by
      interfering with F-protein function.
AB  - Human respiratory syncytial virus (RSV) is a major cause of severe lower
      respiratory tract infection. Infection is critically dependent on the RSV fusion
      (F) protein, which mediates fusion between the viral envelope and airway
      epithelial cells. The F protein is also expressed on infected cells and is
      responsible for fusion of infected cells with adjacent cells, resulting in the
      formation of multinucleate syncytia. The receptor for advanced glycation end
      products (RAGE) is a pattern-recognition receptor that is constitutively highly
      expressed by type I alveolar epithelial cells. Here, we report that RAGE
      protected HEK cells from RSV-induced cell death and reduced viral titres in
      vitro. RAGE appeared to interact directly with the F protein, but, rather than
      inhibiting RSV entry into host cells, virus replication and budding, membrane
      expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and
      sloughing. These data indicate that RAGE may contribute to protecting the lower
      airways from RSV by inhibiting the formation of syncytia, viral spread,
      epithelial damage and airway obstruction. 

PMID- 23559481
TI  - Assessing the relationship between fluctuating asymmetry and cause of death in
      skeletal remains: a test of the developmental origins of health and disease
      hypothesis.
AB  - OBJECTIVES: This study examines the relationship between craniofacial fluctuating
      asymmetry and cause of death in an identified skeletal collection. This study
      tests the Developmental Origins of Health and Disease hypothesis using
      fluctuating asymmetry as the measure of developmental instability. METHODS: The
      skeletal sample used in this study comes from Lisbon, Portugal, and individuals
      in the sample were born between 1806 and 1935. This represents a period during
      which Lisbon was beginning to undergo the modern health transition, in which
      mortality from infectious disease began to decline while mortality from
      degenerative diseases began to increase. Approximately equal numbers of
      individuals in the sample died from infectious diseases, such as tuberculosis,
      and from degenerative diseases. Fluctuating asymmetry is examined using three
      dimensional landmark data collected from 392 individuals with documented causes
      of death. Landmark data may provide a more robust measure of fluctuating
      asymmetry, although it has not often been used in studies of fluctuating
      asymmetry in human skeletal samples. RESULTS: The results of the study show that
      individuals who died from degenerative diseases have higher rates of fluctuating
      asymmetry compared to individuals who died from infectious diseases. Males also
      exhibit higher rates of fluctuating asymmetry compared to females. CONCLUSIONS:
      The results of this study confirm earlier findings that early development has a
      significant impact on adult health outcomes. Furthermore, the results suggest
      that fluctuating asymmetry in skeletal samples may offer a means of testing the
      Developmental Origins of Health and Disease hypothesis.

PMID- 23559482
TI  - Catalytic enantioselective formal hetero-Diels-Alder reactions of enones with
      isatins to give spirooxindole tetrahydropyranones.
AB  - Organocatalytic formal hetero-Diels-Alder reactions of enones with isatins, which
      gave highly enantiomerically enriched functionalized spirooxindole
      tetrahydropyranones via an enamine-based mechanism, were developed. The catalyst
      systems were identified by a screen of combinations of amines, acids, and
      additives. With the identified catalyst systems, various spirooxindole
      tetrahydropyranones were synthesized in high yields with high diastereo- and
      enantioselectivities (see scheme).

PMID- 23559483
TI  - Synthesis and cytostatic and antiviral activities of 2'-deoxy-2',2'-difluororibo-
      and 2'-deoxy-2'-fluororibonucleosides derived from 7-(Het)aryl-7-deazaadenines.
AB  - A series of sugar-modified derivatives of cytostatic 7-heteroaryl-7
      deazaadenosines (2'-deoxy-2'-fluororibo- and 2'-deoxy-2',2'
      difluororibonucleosides) bearing an aryl or heteroaryl group at position 7 was
      prepared and screened for biological activity. The difluororibonucleosides were
      prepared by non- stereoselective glycosidation of 6-chloro-7-deazapurine with
      benzoyl-protected 2-deoxy-2,2-difluoro-D-erythro-pentofuranosyl-1-mesylate,
      followed by amination and aqueous Suzuki cross-couplings with (het)arylboronic
      acids. The fluororibo derivatives were prepared by aqueous palladium-catalyzed
      cross-coupling reactions of the corresponding 7-iodo-7-deazaadenine 2'-deoxy-2'
      fluororibonucleoside 20 with (het)arylboronic acids. The key intermediate 20 was
      prepared by a six-step sequence from the corresponding arabinonucleoside by
      selective protection of 3'- and 5'-hydroxy groups with acid-labile groups,
      followed by stereoselective SN 2 fluorination and deprotection. Some of the title
      nucleosides and 7-iodo-7-deazaadenine intermediates showed micromolar cytostatic
      or anti-HCV activity. The most active were 7-iodo and 7-ethynyl derivatives. The
      corresponding 2'-deoxy-2',2'-difluororibonucleoside 5'-O-triphosphates were found
      to be good substrates for bacterial DNA polymerases, but are inhibitors of human
      polymerase alpha.

PMID- 23559484
TI  - Formability and mechanical properties of porous titanium produced by a moldless
      process.
AB  - Tailor-made porous titanium implants show great promise in both orthopedic and
      dental applications. However, traditional powder metallurgical processes require
      a high-cost mold, making them economically unviable for producing unique devices.
      In this study, a mixture of titanium powder and an inlay wax binder was developed
      for moldless forming and sintering. The formability of the mixture, the
      dimensional changes after sintering, and the physical and mechanical properties
      of the sintered porous titanium were evaluated. A 90:10 wt % mixture of Ti powder
      and wax binder was created manually at 70 degrees C. After debindering, the
      specimen was sintered in Ar at 1100 degrees C without any mold for 1, 5, and 10
      h. The shrinkage, porosity, absorption ratio, bending and compressive strength,
      and elastic modulus were measured. The bending strength (135-356 MPa),
      compression strength (178-1226 MPa), and elastic modulus (24-54 GPa) increased
      with sintering time; the shrinkage also increased, whereas the porosity (from
      37.1 to 29.7%) and absorption ratio decreased. The high formability of the
      binder/metal powder mixture presents a clear advantage for fabricating tailor
      made bone and hard tissue substitution units. Moreover, the sintered compacts
      showed high strength and an elastic modulus comparable to that of cortical bone.

PMID- 23559485
TI  - Micelle-enhanced spectrofluorimetric method for determination of sitagliptin and
      identification of potential alkaline degradation products using LC-MS.
AB  - A novel, quick, simple and highly sensitive spectrofluorimetric method was
      developed and validated for the determination of sitagliptin (SG) in its
      pharmaceutical formulations. The proposed method is based on investigation of the
      fluorescence spectral behavior of sitagliptin in an SDS micellar system. In an
      aqueous solution of phosphate buffer pH 4.0, the fluorescence intensity of SG in
      the presence of SDS was greatly enhanced, by 200%, i.e. twofold enhancement. The
      fluorescence intensity of SG was measured at 300 nm after excitation at 270 nm.
      The method showed good linearity in the range 0.03-10.0 ug/mL with a good
      correlation coefficient (r = 0.9998). The limits of detection and quantitation
      values were 5.31 and 16.1 ng/mL, respectively. The proposed method was
      successfully applied to the analysis of SG in its single and co-formulated
      commercial tablets; the results were in good agreement with those obtained using
      a reference method. Application of the proposed method was extended to stability
      studies of SG after exposure to different forced degradation conditions according
      to the ICH guidelines, such as acidic, alkaline, thermal, photo- and oxidative
      stress. The chemical structure of certain potential degradation products (DPs)
      were investigated using LC-MS.

PMID- 23559486
TI  - Noncontrast-enhanced magnetic resonance angiography and venography imaging with
      enhanced angiography.
AB  - PURPOSE: To achieve simultaneous high-resolution magnetic resonance angiography
      and venography (MRAV) imaging in terms of enhanced time-of-flight (TOF)
      angiography and susceptibility-weighted imaging (SWI), with a clear separation of
      arteries and veins. MATERIALS AND METHODS: A new flow rephase/dephase interleaved
      double-echo sequence was introduced that facilitates multiple types of imaging
      contrast, i.e., TOF, SWI, and dark blood, in a single acquisition. A nonlinear
      subtraction (NLS) method is proposed and assessed to maximally enhance
      angiography contrast with minimum venous contamination. RESULTS: Fully flow
      rephased TOF MRA and SWI MRV data were acquired simultaneously, along with an
      extra flow dephased dark blood image for angiography enhancement calculation.
      Compared to linear subtraction methods, the proposed NLS method was able to
      enhance angiography contrast while effectively eliminating vein-tissue contrast.
      The NLS method even outperformed low-dose contrast-enhanced MRA for a clean,
      enhanced angiography map. CONCLUSION: Using the proposed interleaved double-echo
      sequence along with the NLS postprocessing method, one can simultaneously obtain
      both high-quality SWI and significantly enhanced TOF MRA with clear separation of
      arterial and venous maps.

PMID- 23559487
TI  - An update on the management of hepatitis C: guidelines for protease inhibitor
      based triple therapy from the Latin American Association for the Study of the
      Liver.
AB  - Hepatitis C is a common cause of end-stage liver disease, and the main indication
      for liver transplantation in Latin America. Treatment of hepatitis C infected
      patients improves important long-term outcomes as mortality. Sustained viral
      response is reached in near 50% of patients with the previous management based in
      pegylated interferon and ribavirin. Recently new drugs were available increasing
      sustained viral response significantly, changing the standard of care to triple
      therapy. This guidelines provides a framework for practitioner in Latin America,
      to the management of patients with hepatitis C chronic infection. 

PMID- 23559488
TI  - An adolescent with pseudomigraine, transient headache, neurological deficits, and
      lymphocytic pleocytosis (HaNDL Syndrome): case report and review of the
      literature.
AB  - We report a 16-year-old adolescent with 2 episodes of focal neurological
      deficits, pseudomigrainous headache, and lymphocytic pleocytosis due to the
      syndrome of transient headache and neurological deficits with cerebrospinal fluid
      (CSF) lymphocytosis (HaNDL), also known as pseudomigraine with CSF pleocytosis.
      Review of the literature identifies 13 additional cases of HaNDL in the pediatric
      population. These cases are reviewed and evidence for possible etiopathogenesis
      is discussed. This syndrome may mimic much more common conditions such as
      complicated or hemiplegic migraine, aseptic meningitis, meningoencephalitis, or
      stroke. However, HaNDL differs from complicated or hemiplegic migraine and stroke
      since CSF pleocytosis is uniformly present. There are many infectious conditions
      that can present with neurological deficits, headache, and CSF pleocytosis, but
      the transient nature of the deficits and lack of a consistently identifiable
      infectious etiology despite extensive evaluations typify HaNDL. This clinical
      syndrome is underrecognized and underreported. HaNDL remains a diagnosis of
      exclusion.

PMID- 23559489
TI  - Recurrent Wernicke encephalopathy in an adolescent female following laparoscopic
      gastric bypass surgery.

PMID- 23559490
TI  - Characterization of human cortical gene expression in relation to glucose
      utilization.
AB  - OBJECTIVES: Human brain development follows a unique pattern characterized by a
      prolonged period of postnatal growth and reorganization, and a postnatal peak in
      glucose utilization. The molecular processes underlying these developmental
      changes are poorly characterized. The objectives of this study were to determine
      developmental trajectories of gene expression and to examine the evolutionary
      history of genes differentially expressed as a function of age. METHODS: We used
      microarrays to determine age-related patterns of mRNA expression in human
      cerebral cortical samples ranging from infancy to adulthood. In contrast to
      previous developmental gene expression studies of human neocortex that relied on
      postmortem tissue, we measured mRNA expression from the nondiseased margins of
      surgically resected tissue. We used regression models designed to identify
      transcripts that followed significant linear or curvilinear functions of age and
      used population genetics techniques to examine the evolution of these genes.
      RESULTS: We identified 40 transcripts with significant age-related trajectories
      in expression. Ten genes have documented roles in nervous system development and
      energy metabolism, others are novel candidates in brain development. Sixteen
      transcripts showed similar patterns of expression, characterized by decreasing
      expression during childhood. Comparative genomic analyses revealed that the
      regulatory regions of three genes have evidence of adaptive evolution in recent
      human evolution. CONCLUSIONS: These findings provide evidence that a subset of
      genes expressed in the human cerebral cortex broadly mirror developmental
      patterns of cortical glucose consumption. Whether there is a causal relationship
      between gene expression and glucose utilization remains to be determined.

PMID- 23559491
TI  - TIPS-TTF as a precursor of low-symmetry TTF derivatives: steric protection
      strategy in the regioselective C-H modification of TTF.
AB  - Triisopropylsilyltetrathiafulvalene (TIPS-TTF) has been devised as a promising
      platform for the synthesis of low-symmetry TTF derivatives. The bulky TIPS group
      allows TIPS-TTF to undergo palladium-catalyzed direct diarylation as well as LDA
      mediated dilithiation exclusively on the roomier dithiole ring. Subsequent
      fluoride-mediated protodesilylation provided vicinally difunctionalized TTF,
      which could undergo further functionalization.

PMID- 23559493
TI  - Neutrophils promote 6-sulfo LacNAc+ dendritic cell (slanDC) survival.
AB  - There is increasing evidence supporting the notion that neutrophils and other
      leukocytes establish cooperative actions in regulating innate and adaptive immune
      responses. In such a context, we have shown recently that human neutrophils
      amplify NK cell/slanDC-mediated cytokine production by directly costimulating IFN
      gamma production by NK cells, as well as by potentiating IL-12p70 release by
      slanDCs via CD18/ICAM-1 interactions. To gain more insights into the molecular
      bases of the neutrophil-mediated cytokine potentiation by NK cells and slanDCs
      under coculture conditions, we now report that neutrophils efficaciously maintain
      slanDC survival by contact-dependent mechanisms. Such a phenomenon occurs in the
      absence or presence of NK cells, which, in the presence of LPS and IL-2 or the IL
      15/IL-18 combination, accelerates slanDC apoptosis significantly. Noteworthy,
      alphaICAM-1- and alphaCD18-neutralizing antibodies, previously shown to suppress
      IL-12p70 production by slanDCs and consequently, IFN-gamma by NK cells under
      similar experimental conditions, did not minimally alter the neutrophil-mediated
      prosurvival effect on slanDCs. Altogether, data not only expand our knowledge on
      the interactions between human neutrophils and slanDCs but also prove that
      neutrophil-mediated promotion of slanDC survival and potentiation of slanDC
      derived IL-12p70 occur via different mechanisms. 

PMID- 23559492
TI  - G-CSF activation of AKT is not sufficient to prolong neutrophil survival.
AB  - Neutrophils play an important role in the innate immune response against
      bacterial and fungal infections. They have a short lifespan in circulation, and
      their survival can be modulated by several cytokines, including G-CSF. Previous
      studies have implicated AKT as a critical signaling intermediary in the
      regulation of neutrophil survival. Our results demonstrate that G-CSF activation
      of AKT is not sufficient to prolong neutrophil survival. Neutrophils treated with
      G-CSF undergo apoptosis, even in the presence of high levels of p-AKT. In
      addition, inhibitors of AKT and downstream targets failed to alter neutrophil
      survival. In contrast, neutrophil precursors appear to be dependent on AKT
      signaling pathways for survival, whereas high levels of p-AKT inhibit
      proliferation. Our data suggest that the AKT/mTOR pathway, although important in
      G-CSF-driven myeloid differentiation, proliferation, and survival of early
      hematopoietic progenitors, is less essential in G-CSF suppression of neutrophil
      apoptosis. Whereas basal AKT levels may be required for the brief life of
      neutrophils, further p-AKT expression is not able to extend the neutrophil
      lifespan in the presence of G-CSF.

PMID- 23559494
TI  - An efficient bioorthogonal strategy using CuAAC click chemistry for
      radiofluorinations of SNEW peptides and the role of copper depletion.
AB  - The EphB2 receptor is known to be overexpressed in various types of cancer and is
      therefore a promising target for tumor cell imaging by positron emission
      tomography (PET). In this regard, imaging could facilitate the early detection of
      EphB2-overexpressing tumors, monitoring responses to therapy directed toward
      EphB2, and thus improvement in patient outcomes. We report the synthesis and
      evaluation of several fluorine-18-labeled peptides containing the SNEW amino acid
      motif, with high affinity for the EphB2 receptor, for their potential as
      radiotracers in the non-invasive imaging of cancer using PET. For the purposes of
      radiofluorination, EphB2-antagonistic SNEW peptides were varied at the C terminus
      by the introduction of L-cysteine, and further by alkyne- or azide-modified amino
      acids. In addition, two novel bifunctional and bioorthogonal labeling building
      blocks [(18)F]AFP and [(18)F]BFP were applied, and their capacity to introduce
      fluorine-18 was compared with that of the established building block [(18)F]FBAM.
      Copper-assisted Huisgen 1,3-dipolar cycloaddition, which belongs to the set of
      bioorthogonal click chemistry reactions, was used to introduce both novel
      building blocks into azide- or alkyne-modified SNEW peptides under mild
      conditions. Finally, the depletion of copper immediately after radiolabeling is a
      highly important step of this novel methodology.

PMID- 23559495
TI  - Biointeractivity-related versus chemi/physisorption-related apatite precursor
      forming ability of current root end filling materials.
AB  - Commercial root end filling materials, namely two zinc oxide eugenol-based
      cements [intermediate restorative material (IRM), Superseal], a glass ionomer
      cement (Vitrebond) and three calcium-silicate mineral trioxide aggregate (MTA)
      based cements (ProRoot MTA, MTA Angelus, and Tech Biosealer root end), were
      examined for their ability to: (a) release calcium (Ca(2+) ) and hydroxyl (OH(-)
      ) ions (biointeractivity) and (b) form apatite (Ap) and/or calcium phosphate
      (CaP) precursors. Materials were immersed in Hank's balanced salt solution (HBSS)
      for 1-28 days. Ca(2+) and OH(-) release were measured by ion selective probes,
      surface analysis was performed by environmental scanning electron
      microscopy/energy dispersive X-ray analysis, micro-Raman, and Fourier transform
      infrared spectroscopy. IRM and Superseal released small quantities of Ca(2+) and
      no OH(-) ions. Uneven sparse nonapatitic Ca-poor amorphous CaP (ACP) deposits
      were observed after 24 h soaking. Vitrebond did not release either Ca(2+) or OH(
      ) ions, but uneven nonapatitic Ca-poor CaP deposits were detected after 7 days
      soaking. ProRoot MTA, MTA Angelus, and Tech Biosealer root end released
      significant amounts of Ca(2+) and OH(-) ions throughout the experiment. After 1
      day soaking, nanospherulites of CaP deposits formed by amorphous
      calcium/magnesium phosphate (ACP) Ap precursors were detected. A more mature ACP
      phase was present on ProRoot MTA and on Tech Biosealer root end at all times. In
      conclusion, zinc oxide and glass ionomer cements had little or no ability to
      release mineralizing ions: they simply act as substrates for the possible
      chemical bonding/adsorption of environmental ions and precipitation of
      nonapatitic Ca-poor ACP deposits. On the contrary, calcium-silicate cements
      showed a high calcium release and basifying effect and generally a pronounced
      formation of more mature ACP apatitic precursors correlated with their higher ion
      releasing ability.

PMID- 23559496
TI  - Reply: To PMID 23281277.

PMID- 23559498
TI  - Intermolecular gold(I)-catalyzed cyclization of furans with alkynes: formation of
      phenols and indenes.
AB  - A heart of gold: Phenols can be obtained by the intermolecular reaction of furans
      with alkynes by using [AuIPr](+)A(-) catalysts (see scheme). 1,3
      Diphenylisobenzofuran also reacts via a cyclopropyl gold carbene to selectively
      form 2,3-disubstituted indenes. (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2
      ylidene; A = anion.).

PMID- 23559497
TI  - Diffusion tensor MRI evaluation of the corona radiata, cingulate gyri, and corpus
      callosum in HIV patients.
AB  - PURPOSE: To evaluate the white matter integrity of the corona radiata, cingulate
      gyri, and corpus callosum in patients with human immunodeficiency virus (HIV)
      infection through diffusion tensor imaging (DTI). MATERIALS AND METHODS: Thirty
      four patients with at least 5 years of HIV infection and 27 healthy controls
      underwent magnetic resonance imaging (MRI) in a 1.5 T scanner. A voxelwise-based
      technique was used to analyze the DTI data. RESULTS: We found that in the body of
      corpus callosum the fractional anisotropy (FA) was significantly reduced, whereas
      mean diffusivity (MD) and radial diffusivity (RD) were increased in HIV patients.
      Analyzing the corona radiata, axial diffusivity (AD) and MD were significantly
      increased in the left superior region, MD and RD were increased in the left
      posterior area, and, furthermore, MD was also increased in the right posterior
      region. No significant abnormalities were found on the cingulate gyri. The white
      matter damage, related to FA reduction, was associated with increased RD,
      indicating that demyelization might be the pathophysiological result of this
      damage. CONCLUSION: Since the DTI can detect abnormalities in the normal
      appearing white matter, this technique may play a role as an early marker of HIV
      disease progression, including clinical manifestations such as cognitive
      impairment.

PMID- 23559499
TI  - Exploring nitrogen ligand diversity in trans-N-heterocyclic carbene-amine
      platinum complexes: synthesis, characterization, and application to fluorescence.
AB  - Expand and diversify your Ptfolio: N-Heterocyclic carbene-Pt-pyridine complexes
      have been used to generate an expanded and diversified set of trans NHC-Pt
      complexes with various amines, polyamines, hydroxylamines, or hydrazine as
      ligands. Attachment of a fluorophore moiety has also been successfully achieved.

PMID- 23559500
TI  - 25-hydroxyvitamin D levels in African American and Nigerian women.
AB  - OBJECTIVES: African Americans (AA) have substantially lower levels of circulating
      25-hydroxyvitamin D (25(OH)D) than whites. We compared population-based samples
      of 25(OH)D in women of African descent from Nigeria and metropolitan Chicago.
      METHODS: One hundred women of Yoruba ethnicity from southwest Nigeria and 94
      African American women from metropolitan Chicago were recruited and compared
      using a standardized survey protocol and the same laboratory assay for 25(OH)D.
      RESULTS: Mean 25(OH)D levels were 64 nmol/l among the Nigerians and 29 nmol/l
      among the AA. Only 10% of the values were shared in common between the groups,
      and 76% of the Nigerians were above the currently defined threshold for adequate
      circulating 25(OH)D compared to 5% of the AA. Modest associations were seen
      between 25(OH)D and measures of obesity, although adjustment for these traits did
      not materially affect the group differences. CONCLUSION: These data support the
      presumption that skin color is an adaptive trait which has evolved in part to
      regulate 25(OH)D. It remains undetermined, however, whether lower values observed
      in AA have negative health consequences.

PMID- 23559501
TI  - Micro-nanopatterning as tool to study the role of physicochemical properties on
      cell-surface interactions.
AB  - The current nano-biotechnologies interfacing synthetic materials and cell biology
      requires a better understanding of cell-surface interactions on the micro-to
      nanometer scale. Cell-substrate interactions are mediated by the presence of
      proteins adsorbed from biological fluids to the substrate. The effect of
      nanotopography and surface chemistry on protein adsorption as well as the
      mediation effect on subsequent cellular communication with substratum is not well
      documented. This review discusses the role of physicochemical properties of cell
      surface interactions and state-of-the-art methods currently available for micro
      nanoscale surface fabrication and patterning. We also briefly discuss the current
      surface patterning techniques that allow the combination of a fine and
      independent control on nanotopography and chemistry to understand the effect of
      surface nanoscale substrate morphology on cell-surface interactions which has
      never been realized in previous reports. In addition, we discuss the influence of
      various chemical patterning and modulation of the nano-topography of surfaces on
      cell functionality and phenotype.

PMID- 23559502
TI  - Development of a handoff evaluation tool for shift-to-shift physician handoffs:
      the Handoff CEX.
AB  - BACKGROUND: Increasing frequency of shift-to-shift handoffs coupled with
      regulatory requirements to evaluate handoff quality make a handoff evaluation
      tool necessary. OBJECTIVE: To develop a handoff evaluation tool. DESIGN: Tool
      development. SETTING: Two academic medical centers. SUBJECTS: Nurse
      practitioners, medicine housestaff, and hospitalist attendings. INTERVENTION:
      Concurrent peer and external evaluations of shift-to-shift handoffs.
      MEASUREMENTS: The Handoff CEX (clinical evaluation exercise) consists of 6
      subdomains and 1 overall assessment, each scored from 1 to 9, where 1 to 3 is
      unsatisfactory and 7 to 9 is superior. We assessed range of scores, performance
      among subgroups, internal consistency, and agreement among types of raters.
      RESULTS: We conducted 675 evaluations of 97 unique individuals during 149 handoff
      sessions. Scores ranged from unsatisfactory to superior in each domain. The
      highest rated domain for handoff providers was professionalism (median: 8;
      interquartile range [IQR]: 7-9); the lowest was content (median: 7; IQR: 6-8).
      Scores at the 2 institutions were similar, and scores did not differ
      significantly by training level. Spearman correlation coefficients among the CEX
      subdomains for provider scores ranged from 0.71 to 0.86, except for setting (0.39
      0.40). Third-party external evaluators consistently gave lower marks for the same
      handoff than peer evaluators did. Weighted kappa scores for provider evaluations
      comparing external evaluators to peers ranged from 0.28 (95% confidence interval
      [CI]: 0.01, 0.56) for setting to 0.59 (95% CI: 0.38, 0.80) for organization.
      CONCLUSIONS: This handoff evaluation tool was easily used by trainees and
      attendings, had high internal consistency, and performed similarly across
      institutions. Because peers consistently provided higher scores than external
      evaluators, this tool may be most appropriate for external evaluation.

PMID- 23559503
TI  - Recruiting hospitalized patients for research: how do participants differ from
      eligible nonparticipants?
AB  - BACKGROUND: Randomized controlled trials provide strong evidence for guidelines
      and interventions. Yet, much of the eligible population declines to be studied.
      OBJECTIVE: To identify differences between participants and eligible
      nonparticipants in (1) perceived stress, (2) self-efficacy, (3) recovery
      expectations, (4) discussing advance directives, and (5) understanding a standard
      prescription label (health literacy). DESIGN: Quasi-experimental prospective
      cohort study in 5 acute-care hospitals. METHODS: We approached 295 hospital
      inpatients as they were being recruited for a behavioral intervention and asked
      them to answer 5 screening questions. We matched respondents' answers to their
      acceptance of the behavioral intervention and to Medicare claims and enrollment
      data. We used multivariate logistic regression to compare consent rates based on
      screening-question responses. SETTING/PATIENTS: Hospitalized fee-for-service
      Medicare patients. RESULTS: Patients were less likely to consent to the
      behavioral intervention when they reported feeling unable to control important
      things in their lives (odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.14
      0.92), had low recovery expectations (OR: 0.17, 95% CI: 0.06-0.45), or were
      confused by any question (OR: 0.11, 95% CI: 0.05-0.24). Conversely, individuals
      who answered the medication question incorrectly were more likely to consent to
      the behavioral intervention (OR: 3.82, 95% CI: 1.12-13.03). There were no
      significant differences in consent for patients who reported feeling overwhelmed
      or reported discussing advance care planning with family members or doctors.
      CONCLUSIONS: Hospitalized eligible nonparticipants differ in constructs related
      to perceived stress, recovery expectation, and health literacy. Recognizing such
      characteristics may inform strategies to improve intervention recruitment in the
      hospital and representation in clinical trials.

PMID- 23559504
TI  - Impact of reduced k-space acquisition on pathologic detectability for volumetric
      MR spectroscopic imaging.
AB  - PURPOSE: To assess the impact of accelerated acquisitions on the spectral quality
      of volumetric magnetic resonance spectroscopic imaging (MRSI) and to evaluate
      their ability in detecting metabolic changes with mild injury. MATERIALS AND
      METHODS: The implementation of a generalized autocalibrating partially parallel
      acquisition (GRAPPA) method for a high-resolution whole-brain echo planar SI (3D
      EPSI) sequence is first described and the spectral accuracy of the GRAPPA-EPSI
      method is investigated using lobar and voxel-based analyses for normal subjects
      and patients with mild traumatic brain injuries (mTBI). The performance of GRAPPA
      was compared with that of fully encoded EPSI for five datasets collected from
      normal subjects at the same scanning session, as well as on 45 scans (20 normal
      subjects and 25 mTBI patients) for which the reduced k-space sampling was
      simulated. For comparison, a central k-space lower-resolution 3D-EPSI acquisition
      was also simulated. Differences in individual metabolites and metabolite ratio
      distributions of the mTBI group relative to those of age-matched control subjects
      were statistically evaluated using analyses divided into hemispheric brain lobes
      and tissue types. RESULTS: GRAPPA-EPSI with 16-minute scan time yielded robust
      and similar results in terms of MRSI quantitation, spectral fitting, and accuracy
      with that of fully sampled 3D-EPSI acquisitions and was more accurate than
      central k-space acquisition. Primary findings included high correlations
      (accuracy of 92.6%) between the GRAPPA and fully sampled results. CONCLUSION:
      Although the reduced encoding method is associated with lower signal-to-noise
      ratio (SNR) that impacts the quality of spectral analysis, the use of the
      parallel imaging method can lead to the same diagnostic outcomes as the fully
      sampled data when using the sensitivity-limited volumetric MRSI.

PMID- 23559505
TI  - Visual analysis of cardiac 4D MRI blood flow using line predicates.
AB  - Four-dimensional MRI is an in vivo flow imaging modality that is expected to
      significantly enhance the understanding of cardiovascular diseases. Among other
      fields, 4D MRI provides valuable data for the research of cardiac blood flow and
      with that the development, diagnosis, and treatment of various cardiac
      pathologies. However, to gain insights from larger research studies or to apply
      4D MRI in the clinical routine later on, analysis techniques become necessary
      that allow to robustly identify important flow characteristics without demanding
      too much time and expert knowledge. Heart muscle contractions and the particular
      complexity of the flow in the heart imply further challenges when analyzing
      cardiac blood flow. Working toward the goal of simplifying the analysis of 4D MRI
      heart data, we present a visual analysis method using line predicates. With line
      predicates precalculated integral lines are sorted into bundles with similar flow
      properties, such as velocity, vorticity, or flow paths. The user can combine the
      line predicates flexibly and by that carve out interesting flow features helping
      to gain overview. We applied our analysis technique to 4D MRI data of healthy and
      pathological hearts and present several flow aspects that could not be shown with
      current methods. Three 4D MRI experts gave feedback and confirmed the additional
      benefit of our method for their understanding of cardiac blood flow.

PMID- 23559506
TI  - Ambient occlusion effects for combined volumes and tubular geometry.
AB  - This paper details a method for interactive direct volume rendering that computes
      ambient occlusion effects for visualizations that combine both volumetric and
      geometric primitives, specifically tube-shaped geometric objects representing
      streamlines, magnetic field lines or DTI fiber tracts. The algorithm extends the
      recently presented the directional occlusion shading model to allow the rendering
      of those geometric shapes in combination with a context providing 3D volume,
      considering mutual occlusion between structures represented by a volume or
      geometry. Stream tube geometries are computed using an effective spline-based
      interpolation and approximation scheme that avoids self-intersection and
      maintains coherent orientation of the stream tube segments to avoid surface
      deforming twists. Furthermore, strategies to reduce the geometric and specular
      aliasing of the stream tubes are discussed.

PMID- 23559507
TI  - A maxent-stress model for graph layout.
AB  - In some applications of graph visualization, input edges have associated target
      lengths. Dealing with these lengths is a challenge, especially for large graphs.
      Stress models are often employed in this situation. However, the traditional full
      stress model is not scalable due to its reliance on an initial all-pairs shortest
      path calculation. A number of fast approximation algorithms have been proposed.
      While they work well for some graphs, the results are less satisfactory on graphs
      of intrinsically high dimension, because some nodes may be placed too close
      together, or even share the same position. We propose a solution, called the
      maxent-stress model, which applies the principle of maximum entropy to cope with
      the extra degrees of freedom. We describe a force-augmented stress majorization
      algorithm that solves the maxent-stress model. Numerical results show that the
      algorithm scales well, and provides acceptable layouts for large, nonrigid
      graphs. This also has potential applications to scalable algorithms for
      statistical multidimensional scaling (MDS) with variable distances.

PMID- 23559508
TI  - A divide-and-conquer approach to quad remeshing.
AB  - Many natural and man-made objects consist of simple primitives, similar
      components, and various symmetry structures. This paper presents a divide-and
      conquer quadrangulation approach that exploits such global structural
      information. Given a model represented in triangular mesh, we first segment it
      into a set of submeshes, and compare them with some predefined quad mesh
      templates. For the submeshes that are similar to a predefined template, we remesh
      them as the template up to a number of subdivisions. For the others, we adopt the
      wave-based quadrangulation technique to remesh them with extensions to preserve
      symmetric structure and generate compatible quad mesh boundary. To ensure that
      the individually remeshed submeshes can be seamlessly stitched together, we
      formulate a mixed-integer optimization problem and design a heuristic solver to
      optimize the subdivision numbers and the size fields on the submesh boundaries.
      With this divider-and-conquer quadrangulation framework, we are able to process
      very large models that are very difficult for the previous techniques. Since the
      submeshes can be remeshed individually in any order, the remeshing procedure can
      run in parallel. Experimental results showed that the proposed method can
      preserve the high-level structures, and process large complex surfaces robustly
      and efficiently.

PMID- 23559509
TI  - CiSE: a circular spring embedder layout algorithm.
AB  - We present a new algorithm for automatic layout of clustered graphs using a
      circular style. The algorithm tries to determine optimal location and orientation
      of individual clusters intrinsically within a modified spring embedder.
      Heuristics such as reversal of the order of nodes in a cluster and swap of
      neighboring node pairs in the same cluster are employed intermittently to further
      relax the spring embedder system, resulting in reduced inter-cluster edge
      crossings. Unlike other algorithms generating circular drawings, our algorithm
      does not require the quotient graph to be acyclic, nor does it sacrifice the edge
      crossing number of individual clusters to improve respective positioning of the
      clusters. Moreover, it reduces the total area required by a cluster by using the
      space inside the associated circle. Experimental results show that the execution
      time and quality of the produced drawings with respect to commonly accepted
      layout criteria are quite satisfactory, surpassing previous algorithms. The
      algorithm has also been successfully implemented and made publicly available as
      part of a compound and clustered graph editing and layout tool named CHISIO.

PMID- 23559510
TI  - Depth-fighting aware methods for multifragment rendering.
AB  - Many applications require operations on multiple fragments that result from ray
      casting at the same pixel location. To this end, several approaches have been
      introduced that process for each pixel one or more fragments per rendering pass,
      so as to produce a multifragment effect. However, multifragment rasterization is
      susceptible to flickering artifacts when two or more visible fragments of the
      scene have identical depth values. This phenomenon is called coplanarity or Z
      fighting and incurs various unpleasant and unintuitive results when rendering
      complex multilayer scenes. In this work, we develop depth-fighting aware
      algorithms for reducing, eliminating and/or detecting related flaws in scenes
      suffering from duplicate geometry. We adapt previously presented single and
      multipass rendering methods, providing alternatives for both commodity and modern
      graphics hardware. We report on the efficiency and robustness of all these
      alternatives and provide comprehensive comparison results. Finally, visual
      results are offered illustrating the effectiveness of our variants for a number
      of applications where depth accuracy and order are of critical importance.

PMID- 23559511
TI  - Interpenetration free simulation of thin shell rigid bodies.
AB  - We propose a new algorithm for rigid body simulation that guarantees each body is
      in an interpenetration free state, both increasing the accuracy and robustness of
      the simulation as well as alleviating the need for ad hoc methods to separate
      bodies for subsequent simulation and rendering. We cleanly separate collision and
      contact resolution such that objects move and collide in the first step, with
      resting contact handled in the second step. The first step of our algorithm
      guarantees that each time step produces geometry that does not intersect or
      overlap by using an approximation to the continuous collision detection (and
      response) problem and, thus, is amenable to thin shells and degenerately flat
      objects moving at high speeds. In addition, we introduce a novel fail-safe that
      allows us to resolve all interpenetration without iterating to convergence. Since
      the first step guarantees a noninterfering state for the geometry, in the second
      step we propose a contact model for handling thin shells in proximity considering
      only the instantaneous locations at the ends of the time step.

PMID- 23559512
TI  - Multiverse data-flow control.
AB  - In this paper, we present a data-flow system which supports comparative analysis
      of time-dependent data and interactive simulation steering. The system creates
      data on-the-fly to allow for the exploration of different parameters and the
      investigation of multiple scenarios. Existing data-flow architectures provide no
      generic approach to handle modules that perform complex temporal processing such
      as particle tracing or statistical analysis over time. Moreover, there is no
      solution to create and manage module data, which is associated with alternative
      scenarios. Our solution is based on generic data-flow algorithms to automate this
      process, enabling elaborate data-flow procedures, such as simulation, temporal
      integration or data aggregation over many time steps in many worlds. To hide the
      complexity from the user, we extend the World Lines interaction techniques to
      control the novel data-flow architecture. The concept of multiple, special
      purpose cursors is introduced to let users intuitively navigate through time and
      alternative scenarios. Users specify only what they want to see, the decision
      which data are required is handled automatically. The concepts are explained by
      taking the example of the simulation and analysis of material transport in levee
      breach scenarios. To strengthen the general applicability, we demonstrate the
      investigation of vortices in an offline-simulated dam-break data set.

PMID- 23559513
TI  - Understanding visualization: a formal approach using category theory and
      semiotics.
AB  - This paper combines the vocabulary of semiotics and category theory to provide a
      formal analysis of visualization. It shows how familiar processes of
      visualization fit the semiotic frameworks of both Saussure and Peirce, and
      extends these structures using the tools of category theory to provide a general
      framework for understanding visualization in practice, including: Relationships
      between systems, data collected from those systems, renderings of those data in
      the form of representations, the reading of those representations to create
      visualizations, and the use of those visualizations to create knowledge and
      understanding of the system under inspection. The resulting framework is
      validated by demonstrating how familiar information visualization concepts (such
      as literalness, sensitivity, redundancy, ambiguity, generalizability, and chart
      junk) arise naturally from it and can be defined formally and precisely. This
      paper generalizes previous work on the formal characterization of visualization
      by, inter alia, Ziemkiewicz and Kosara and allows us to formally distinguish
      properties of the visualization process that previous work does not.

PMID- 23559514
TI  - Visual analysis and steering of flooding simulations.
AB  - We present a visualization tool for the real-time analysis of interactively
      steered ensemble-simulation runs, and apply it to flooding simulations.
      Simulations are performed on-the-fly, generating large quantities of data. The
      user wants to make sense of the data as it is created. The tool facilitates
      understanding of what happens in all scenarios, where important events occur, and
      how simulation runs are related. We combine different approaches to achieve this
      goal. To maintain an overview, data are aggregated and embedded into the
      simulation rendering, showing trends, outliers, and robustness. For a detailed
      view, we use information-visualization views and interactive visual analysis
      techniques. A selection mechanism connects the two approaches. Points of interest
      are selected by clicking on aggregates, supplying data for visual analysis. This
      allows the user to maintain an overview of the ensemble and perform analysis even
      as new data are supplied through simulation steering. Unexpected or unwanted
      developments are detected easily, and the user can focus the exploration on them.
      The solution was evaluated with two case studies focusing on placing and testing
      flood defense measures. Both were evaluated by a consortium of flood simulation
      and defense experts, who found the system to be both intuitive and relevant.

PMID- 23559516
TI  - In vitro inhibition of the transcription factor NF-kappaB and cyclooxygenase by
      bamboo extracts.
AB  - Several bamboo species have been used in traditional medicine for the treatment
      of inflammatory conditions. The present study evaluates the in vitro anti
      inflammatory properties of the traditionally used bamboo species Phyllostachys
      nigra (Lodd.) Munro and Sasa veitchii (Carr.) Rehder to explore their future
      research opportunities and therapeutic potential as anti-inflammatory agents. The
      extracts were evaluated for their potential inhibitory activity at the level of
      NF-kappaB-induced gene expression and suppression of cyclooxygenase (COX)-1 and
      COX-2 enzyme activities, representative pharmacological targets for the anti
      inflammatory action of glucocorticoids and non-steroidal anti-inflammatory drugs,
      respectively. The activity of P. nigra (Lodd.) Munro and S. veitchii (Carr.)
      Rehder was compared with bamboo species without traditional anti-inflammatory
      indications. High-performance liquid chromatography with diode-array detection
      and liquid chromatography-tandem mass spectrometry analyses were performed to
      phytochemically characterize the extracts. P. nigra (Lodd.) Munro leaf extract
      potently inhibited NF-kappaB-induced gene expression, while S. veitchii (Carr.)
      Rehder leaf extract exerted a selective COX-2 inhibition. The crude extracts
      consistently showed a more potent bioactivity than the solid phase extraction
      fractions. P. nigra (Lodd.) Munro and S. veitchii (Carr.) Rehder both exert anti
      inflammatory properties, but act via a different molecular mechanism.

PMID- 23559517
TI  - A solar rechargeable flow battery based on photoregeneration of two soluble redox
      couples.
AB  - Storable sunshine, reusable rays: A solar rechargeable redox flow battery is
      proposed based on the photoregeneration of I(3)(-)/I(-) and
      [Fe(C(10)H(15))(2)](+)/Fe(C(10)H(15))(2) soluble redox couples, which can be
      regenerated by flowing from a discharged redox flow battery (RFB) into a dye
      sensitized solar cell (DSSC) and then stored in tanks for subsequent RFB
      applications This technology enables effective solar-to-chemical energy
      conversion.

PMID- 23559515
TI  - NG2/CSPG4-collagen type VI interplays putatively involved in the
      microenvironmental control of tumour engraftment and local expansion.
AB  - In soft-tissue sarcoma patients, enhanced expression of NG2/CSPG4 proteoglycan in
      pre-surgical primary tumours predicts post-surgical metastasis formation and
      thereby stratifies patients into disease-free survivors and patients destined to
      succumb to the disease. Both primary and secondary sarcoma lesions also up
      regulate collagen type VI, a putative extracellular matrix ligand of NG2, and
      this matrix alteration potentiates the prognostic impact of NG2. Enhanced
      constitutive levels of the proteoglycan in isolated sarcoma cells closely
      correlate with a superior engraftment capability and local growth in xenogenic
      settings. This apparent NG2-associated malignancy was also corroborated by the
      diverse tumorigenic behaviour in vitro and in vivo of immunoselected NG2
      expressing and NG2-deficient cell subsets, by RNAi-mediated knock down of
      endogenous NG2, and by ectopic transduction of full-length or deletion constructs
      of NG2. Cells with modified expression of NG2 diverged in their interaction with
      purified Col VI, matrices supplemented with Col VI, and cell-free matrices
      isolated from wild-type and Col VI null fibroblasts. The combined use of dominant
      negative NG2 mutant cells and purified domain fragments of the collagen allowed
      us to pinpoint the reciprocal binding sites within the two molecules and to
      assert the importance of this molecular interaction in the control of sarcoma
      cell adhesion and motility. The NG2-mediated binding to Col VI triggered
      activation of convergent cell survival- and cell adhesion/migration-promoting
      signal transduction pathways, implicating PI-3K as a common denominator. Thus,
      the findings point to an NG2-Col VI interplay as putatively involved in the
      regulation of the cancer cell-host microenvironment interactions sustaining
      sarcoma progression.

PMID- 23559518
TI  - Recent trends in the management of minor salivary gland carcinoma.
AB  - The current management of minor salivary gland cancer is reviewed. These
      malignancies often present as a submucosal swelling and have been reported at all
      anatomic subsites of the head and neck. Modern imaging is essential in evaluating
      the location and the anatomic extent of disease. An incisional or punch biopsy
      determines the histologic type and grade. Recent advances in molecular biology
      have yielded diagnostic and potential therapeutic targets that may change our
      treatment in the future. Complete resection is the treatment of choice.
      Unfortunately, given the proximity of essential structures, the need to balance
      functional and cosmetic with oncologic consequences can interfere with an
      adequate "clear margin." The neck should be treated when there is evidence of
      regional metastasis or when subclinical metastatic risk exceeds 15%. Surgery
      alone cures most low-stage, low-grade tumors, all other stages and grades require
      postoperative radiotherapy. Systemic treatment for locoregional and distant
      failure remains disappointing.

PMID- 23559519
TI  - Physicochemical regulation of endothelial sprouting in a 3D microfluidic
      angiogenesis model.
AB  - Both physiological and pathological tissue remodeling (e.g., during wound healing
      and cancer, respectively) require new blood vessel formation via angiogenesis,
      but the underlying microenvironmental mechanisms remain poorly defined due in
      part to the lack of biologically relevant in vitro models. Here, we present a
      biomaterials-based microfluidic 3D platform for analysis of endothelial sprouting
      in response to morphogen gradients. This system consists of three
      lithographically defined channels embedded in type I collagen hydrogels. A
      central channel is coated with endothelial cells, and two parallel side channels
      serve as a source and a sink for the steady-state generation of biochemical
      gradients. Gradients of vascular endothelial growth factor (VEGF) promoted
      sprouting, whereby endothelial cell responsiveness was markedly dependent on cell
      density and vessel geometry regardless of treatment conditions. These results
      point toward mechanical and/or autocrine mechanisms that may overwhelm pro
      angiogenic paracrine signaling under certain conditions. To date, neither
      geometrical effects nor cell density have been considered critical determinants
      of angiogenesis in health and disease. This biomimetic vessel platform
      demonstrated utility for delineating hitherto underappreciated contributors of
      angiogenesis, and future studies may enable important new mechanistic insights
      that will inform anti-angiogenic cancer therapy.

PMID- 23559520
TI  - Italian version of the physical therapy patient satisfaction questionnaire: cross
      cultural adaptation and psychometric properties.
AB  - BACKGROUND: Patient satisfaction is an important measure for evaluating
      interventions in health care. No patient satisfaction questionnaire for physical
      therapy treatment has been validated to date for use in an Italian outpatient
      population. OBJECTIVE: The aim of this study was to translate, culturally adapt,
      and validate the Italian version of the Physical Therapy Patient Satisfaction
      Questionnaire (PTPSQ-I). DESIGN: A measurement study was conducted. METHODS: The
      PTPSQ-I was developed through forward-backward translation, final review, and pre
      final version. An acceptability analysis was first conducted. Reliability was
      measured by internal consistency (Cronbach alpha), and a factor analysis was
      applied to investigate the internal structure. Divergent validity was measured by
      comparing the PTPSQ-I with a visual analog scale (VAS) and with a 5-point Likert
      type scale evaluating the global perceived effect (GPE) for the physical therapy
      treatment. RESULTS: The process for developing the PTPSQ-I required 3 months
      using data on 315 outpatients. Based on our initial analyses, 5 items were
      deleted from the PTPSQ-I, which was renamed the PTPSQ-I(15). The PTPSQ-I(15)
      showed high internal consistency (alpha=.905). Divergent validity was moderate
      for the GPE (r=.33) but not significant for the VAS (r=-.07). A factor analysis
      revealed evidence for a 2-factor structure related to perceived "Overall
      Experience" and "Professional Impression" that explained 62% of the total
      variance. A third factor, "Efficiency and Convenience," brought explained total
      variance to near 70%. LIMITATIONS: It may be necessary to add items to the PTPSQ
      I(15) to assess other dimensions not currently represented by these 15 items.
      CONCLUSION: The PTPSQ-I(15) showed good psychometric properties, and its use can
      be recommended with Italian-speaking outpatient populations.

PMID- 23559522
TI  - Psychometric properties of the Mini-Balance Evaluation Systems Test (Mini
      BESTest) in community-dwelling individuals with chronic stroke.
AB  - BACKGROUND: The Mini-Balance Evaluation Systems Test (Mini-BESTest) is a new
      balance assessment, but its psychometric properties have not been specifically
      tested in individuals with stroke. OBJECTIVES: The purpose of this study was to
      examine the reliability and validity of the Mini-BESTest and its accuracy in
      categorizing people with stroke based on fall history. DESIGN: An observational
      measurement study with a test-retest design was conducted. METHODS: One hundred
      six people with chronic stroke were recruited. Intrarater reliability was
      evaluated by repeating the Mini-BESTest within 10 days by the same rater. The
      Mini-BESTest was administered by 2 independent raters to establish interrater
      reliability. Validity was assessed by correlating Mini-BESTest scores with scores
      of other balance measures (Berg Balance Scale, one-leg-standing, Functional Reach
      Test, and Timed "Up & Go" Test) in the stroke group and by comparing Mini-BESTest
      scores between the stroke group and 48 control participants, and between fallers
      (>=1 falls in the previous 12 months, n=25) and nonfallers (n=81) in the stroke
      group. RESULTS: The Mini-BESTest had excellent internal consistency (Cronbach
      alpha=.89-.94), intrarater reliability (intraclass correlation coefficient
      [3,1]=.97), and interrater reliability (intraclass correlation coefficient
      [2,1]=.96). The minimal detectable change at 95% confidence interval was 3.0
      points. The Mini-BESTest was strongly correlated with other balance measures.
      Significant differences in Mini-BESTest total scores were found between the
      stroke and control groups and between fallers and nonfallers in the stroke group.
      In terms of floor and ceiling effects, the Mini-BESTest was significantly less
      skewed than other balance measures, except for one-leg-standing on the nonparetic
      side. The Berg Balance Scale showed significantly better ability to identify
      fallers (positive likelihood ratio=2.6) than the Mini-BESTest (positive
      likelihood ratio=1.8). LIMITATIONS: The results are generalizable only to people
      with mild to moderate chronic stroke. CONCLUSIONS: The Mini-BESTest is a reliable
      and valid tool for evaluating balance in people with chronic stroke.

PMID- 23559521
TI  - Alzheimer disease alters the relationship of cardiorespiratory fitness with brain
      activity during the stroop task.
AB  - BACKGROUND: Despite mounting evidence that physical activity has positive
      benefits for brain and cognitive health, there has been little characterization
      of the relationship between cardiorespiratory (CR) fitness and cognition
      associated brain activity as measured by functional magnetic resonance imaging
      (fMRI). The lack of evidence is particularly glaring for diseases such as
      Alzheimer disease (AD) that degrade cognitive and functional performance.
      OBJECTIVE: The aim of this study was to describe the relationship between
      regional brain activity during cognitive tasks and CR fitness level in people
      with and without AD. DESIGN: A case-control, single-observation study design was
      used. METHODS: Thirty-four individuals (18 without dementia and 16 in the
      earliest stages of AD) completed maximal exercise testing and performed a Stroop
      task during fMRI. RESULTS: Cardiorespiratory fitness was inversely associated
      with anterior cingulate activity in the participants without dementia (r=-.48,
      P=.05) and unassociated with activation in those with AD (P>.7). Weak
      associations of CR fitness and middle frontal cortex were noted. LIMITATIONS: The
      wide age range and the use of a single task in fMRI rather than multiple tasks
      challenging different cognitive capacities were limitations of the study.
      CONCLUSIONS: The results offer further support of the relationship between CR
      fitness and regional brain activity. However, this relationship may be attenuated
      by disease. Future work in this area may provide clinicians and researchers with
      interpretable and dependable regional fMRI biomarker signatures responsive to
      exercise intervention. It also may shed light on mechanisms by which exercise can
      support cognitive function.

PMID- 23559523
TI  - Internal and external focus of attention during gait re-education: an
      observational study of physical therapist practice in stroke rehabilitation.
AB  - BACKGROUND: Focus of attention is known to play an important role in motor skill
      learning, yet little is known about how attention is directed within the context
      of stroke rehabilitation. OBJECTIVE: The aims of this study were: (1) to identify
      physical therapists' use of internal and external focus of attention during gait
      rehabilitation for individuals with hemiplegia following stroke and (2) to use
      the findings to design an experimental study examining the impact of focus of
      attention on learning poststroke. DESIGN: The study design involved direct
      nonparticipation observation of physical therapy treatment sessions. METHODS:
      Eight physical therapy treatment sessions, in which gait rehabilitation was
      taking place, were video recorded. Patients were aged between 36 and 85 years,
      and ranged from 7 to 216 days poststroke; physical therapists had between 3 and
      12 years of experience in stroke rehabilitation. Data analysis took 2 forms: (1)
      clear definitions of internal and external focus of attention were agreed on via
      a consensus group and used to develop an analysis matrix through which incidences
      of instruction and feedback were identified, categorized, and counted; and (2)
      verbal dialogue was transcribed verbatim and transcripts were thematically
      analyzed to provide a detailed description of how instructions and feedback were
      used, illustrated by examples. RESULTS: The use of instructions and feedback
      (internal and external focus) was high; an average of one verbal instruction or
      feedback statement was delivered every 14 seconds. Sixty-seven percent of the
      statements were internally focused, 22% were externally focused, and 11% were of
      mixed focus. Unfocused statements (eg, "good") also were used regularly. Patients
      were frequently encouraged to "think about" their performance. LIMITATIONS:
      Observational data collection methods may result in changes in the behavior of
      those observed, which is a potential source of bias. The small sample size also
      was a limitation of the study. CONCLUSION: Physical therapists frequently
      encouraged patients to be aware of their movements and their performance
      (internal focus). This approach may reduce automaticity and hinder learning and
      retention.

PMID- 23559524
TI  - Effect of therapeutic exercise on pain and disability in the management of
      chronic nonspecific neck pain: systematic review and meta-analysis of randomized
      trials.
AB  - BACKGROUND: Given the prevalence of chronic nonspecific neck pain (CNSNP)
      internationally, attention has increasingly been paid in recent years to
      evaluating the efficacy of therapeutic exercise (TE) in the management of this
      condition. PURPOSE: The purpose of this study was to conduct a current review of
      randomized controlled trials concerning the effect of TE on pain and disability
      among people with CNSNP, perform a meta-analysis, and summarize current
      understanding. DATA SOURCES: Data were obtained from MEDLINE, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), EMBASE, Physiotherapy Evidence
      Database (PEDro), and Cochrane Central Register of Controlled Trials (CENTRAL)
      databases from their inception to August 2012. Reference lists of relevant
      literature reviews also were tracked. STUDY SELECTION: All published randomized
      trials without any restriction regarding time of publication or language were
      considered for inclusion. Study participants had to be symptomatic adults with
      only CNSNP. DATA EXTRACTION: Two reviewers independently selected the studies,
      conducted the quality assessment, and extracted the results. Data were pooled in
      a meta-analysis using a random-effects model. DATA SYNTHESIS: Seven studies met
      the inclusion criteria. Therapeutic exercise proved to have medium and
      significant short-term and intermediate-term effects on pain (g=-0.53, 95%
      confidence interval [CI]=-0.86 to -0.20, and g=-0.45, 95% CI=-0.82 to -0.07,
      respectively) and medium but not significant short-term and intermediate-term
      effects on disability (g=-0.39, 95% CI=-0.86 to 0.07, and g=-0.46, 95% CI=-1.00
      to -0.08, respectively). LIMITATIONS: Only one study investigated the effect of
      TE on pain and disability at follow-up longer than 6 months after intervention.
      CONCLUSIONS: Consistent with other reviews, the results support the use of TE in
      the management of CNSNP. In particular, a significant overall effect size was
      found supporting TE for its effect on pain in both the short and intermediate
      terms.

PMID- 23559525
TI  - Physical therapist-established intensive care unit early mobilization program:
      quality improvement project for critical care at the University of California San
      Francisco Medical Center.
AB  - BACKGROUND: Long-term weakness and disability are common after an intensive care
      unit (ICU) stay. Usual care in the ICU prevents most patients from receiving
      preventative early mobilization. OBJECTIVE: The study objective was to describe a
      quality improvement project established by a physical therapist at the University
      of California San Francisco Medical Center from 2009 to 2011. The goal of the
      program was to reduce patients' ICU length of stay by increasing the number of
      patients in the ICU receiving physical therapy and decreasing the time from ICU
      admission to physical therapy initiation. DESIGN: This study was a 9-month
      retrospective analysis of a quality improvement project. METHODS: An
      interprofessional ICU Early Mobilization Group established and promoted
      guidelines for mobilizing patients in the ICU. A physical therapist was dedicated
      to a 16-bed medical-surgical ICU to provide physical therapy to selected patients
      within 48 hours of ICU admission. Patients receiving early physical therapy
      intervention in the ICU in 2010 were compared with patients receiving physical
      therapy under usual care practice in the same ICU in 2009. RESULTS: From 2009 to
      2010, the number of patients receiving physical therapy in the ICU increased from
      179 to 294. The median times (interquartile ranges) from ICU admission to
      physical therapy evaluation were 3 days (9 days) in 2009 and 1 day (2 days) in
      2010. The ICU length of stay decreased by 2 days, on average, and the percentage
      of ambulatory patients discharged to home increased from 55% to 77%. LIMITATIONS:
      This study relied upon the retrospective analysis of data from 6 collectors, and
      the intervention lacked physical therapy coverage for 7 days per week.
      CONCLUSIONS: The improvements in outcomes demonstrated the value and feasibility
      of a physical therapist-led early mobilization program.

PMID- 23559526
TI  - Comparison of health-related quality of life, work status, and health care
      utilization and costs according to hip and knee joint disease severity: a
      national Australian study.
AB  - BACKGROUND: No population-based studies have investigated how the impact of hip
      and knee joint disease may vary with increasing severity. OBJECTIVE: The purpose
      of this study was to evaluate health-related quality of life (HRQoL), work
      status, and health service utilization and costs according to severity of hip and
      knee joint disease. DESIGN: A national cross-sectional survey was conducted.
      METHODS: Five thousand individuals were randomly selected from the Australian
      electoral roll and invited to complete a questionnaire to screen for doctor
      diagnosed hip arthritis, hip osteoarthritis (OA), knee arthritis, and knee OA.
      Severity was classified by means of Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scores (range=0-100): <7=asymptomatic, 7-38=mild
      moderate, and >=39=severe. Health-related quality of life was evaluated by means
      of the Assessment of Quality of Life (AQoL) instrument (range=-0.04 to 1.00;
      scored worst-best). Self-reported data on work status and health service
      utilization were collected, with health care costs estimated with the use of
      government data. RESULTS: Data were available for 1,157 participants, with 237
      (20%) reporting hip or knee joint disease. Of these, 16% (n=37) were classified
      as asymptomatic, 51% (n=120) as mild-moderate, and 27% (n=64) as severe. The
      severe group reported very low HRQoL (adjusted mean AQoL=0.43, 95% confidence
      interval [95% CI]=0.38-0.47) compared with the mild-moderate group (adjusted mean
      AQoL=0.72, 95% CI=0.69-0.75) and the asymptomatic group (adjusted mean AQoL=0.80,
      95% CI=0.74-0.86). Compared with the asymptomatic group, the severe group was >3
      times less likely to undertake paid work (adjusted odds ratio=0.28, 95% CI=0.09
      0.88) and >4 times less likely to undertake unpaid work (adjusted odds
      ratio=0.24, 95% CI=0.10-0.62). Although physical therapy services were used
      infrequently, primary and specialist care utilization and costs were highest for
      the severe group. LIMITATIONS: Other costs (including physical therapy
      consultations) were unavailable. CONCLUSIONS: A clear pattern of worsening HRQoL,
      reduced work participation, and higher medical care utilization was seen with
      increasing severity of joint disease.

PMID- 23559527
TI  - Building the research capacity of clinical physical therapists using a
      participatory action research approach.
AB  - BACKGROUND: This 2-year study explored the experiences of clinical physical
      therapists who used a participatory action research (PAR) approach to learn about
      the practice of clinical research. OBJECTIVES: The aim of this study was to
      explore the experiences of physical therapists who were conducting clinical
      research, facilitated by a PAR approach. DESIGN: A mixed-methods research design
      was used. METHODS: Physical therapists completed questionnaires, were
      interviewed, and participated in focus groups prior to and after the 1-year
      intervention and 1 year later. The research facilitator took field notes.
      Questionnaire data were analyzed descriptively, and themes were developed from
      the qualitative data. Twenty-five therapists took part in 4 self-selected groups.
      RESULTS: Three groups actively participated in the PAR research projects (n=14).
      The remaining 11 therapists decided not to be involved in clinical research
      projects but took part in the study as participants. After 1 year, one group
      completed the data collection phase of their research project, and a second group
      completed their ethics application. The third group ceased their research project
      but hosted a journal club session. At completion of the study, the experiences of
      the physical therapists were positive, and their confidence in conducting
      research and orientation toward research had increased. The perceptions of
      physical therapists toward research, relationships among individuals, and how the
      clinical projects were structured influenced the success of the projects.
      LIMITATIONS: Only physical therapists of one hospital and no other health care
      practitioners were included in this study. CONCLUSIONS: Fourteen physical
      therapists divided among 3 PAR groups were overall positive about their
      experiences when they conducted a research project together. This finding shows
      that a PAR approach can be used as a novel tool to stimulate research
      participation in clinics.

PMID- 23559528
TI  - Differences in utilisation of gastroprotective drugs between 2001 and 2005 in
      Australia and Nova Scotia, Canada.
AB  - PURPOSE: This study aimed to compare use of histamine H2 receptor antagonists
      (H2RAs) and proton pump inhibitors (PPIs), 2001-2005, in the elderly and social
      security beneficiaries in Australia (AUS) and Nova Scotia, Canada (NS). METHODS:
      Prescription dispensing data were collected for all subsidised H2RAs and PPIs. In
      AUS, dispensing data for concession beneficiaries were obtained from the
      Pharmaceutical Benefits Scheme database. In NS, data were sourced from the
      Pharmacare database. Relevant population data were used to convert to World
      Health Organisation Anatomic Therapeutic Chemical defined daily doses (2005) per
      1000 beneficiaries per day (DDD/1000/day). RESULTS: Overall use of
      gastroprotective agents was similar and rising in NS and AUS (100-160
      DDD/1000/day) over this 5-year time window. However, the proportion of this use
      accounted for by PPIs was far higher in AUS (over 85% by 2005) than in NS (23%
      rising to 35% over the 5 years). In AUS, PPI use rose from 50 to about 140
      DDD/1000/day over the 5 years, whereas PPI use in NS rose slowly to less than 60
      DDD/1000/day by 2005. H2RA use in NS was always high (over 100 DDD/1000/day),
      whereas in AUS, H2RA use fell from 54 to around 24 DDD/1000/day over this period.
      CONCLUSIONS: AUS had much higher use of PPIs than NS over 2001-2005. The
      proportion of PPIs in all gastroprotective agents rose in AUS to be nearly 90%.
      The differences in utilisation during this time window could lead to differences
      in health outcomes from either lower gastro-intestinal bleeding risk or higher
      long-term adverse effects of PPIs.

PMID- 23559530
TI  - Impact of direct-to-consumer genomic testing at long term follow-up.
AB  - BACKGROUND: There are few empirical data to inform the debate surrounding the use
      and regulation of direct-to-consumer (DTC) genome-wide disease risk tests. This
      study aimed to determine the long term psychological, behavioural, and clinical
      impacts of genomic risk testing for common disease. METHODS: The Scripps Genomic
      Health Initiative is a prospective longitudinal cohort study of adults who
      purchased the Navigenics Health Compass, a commercially available genomic test.
      Web based assessments were administered at baseline, short (3 months), and long
      term (1 year) follow-up. RESULTS: 2240 participants completed either or both
      follow-ups and a subset of 1325 completed long term follow-up. There were no
      significant differences from baseline in anxiety (p=0.50), fat intake (p=0.34),
      or exercise (p=0.39) at long term follow-up, and 96.8% of the sample had no test
      related distress. Longitudinal linear mixed model analyses were consistent with
      results of cross-sectional analyses. Screening test completion was associated
      with sharing genomic test results with a physician (36.0% shared; p<0.001) and
      perceived utility of the test (61.5% high perceived utility; p=0.002), but was
      not associated with the genomic risk estimate values themselves. CONCLUSIONS:
      Over a third of DTC genomic test recipients shared their results with their own
      physician during an approximate 1 year follow-up period, and this sharing was
      associated with higher screening test completion. Genomic testing was not
      associated with long term psychological risks, and most participants reportedly
      perceived the test to be of high personal utility.

PMID- 23559531
TI  - Selective hydrodeoxygenation of biomass-derived oxygenates to unsaturated
      hydrocarbons using molybdenum carbide catalysts.
AB  - Which cleavage do you prefer? With a combination of density functional theory
      (DFT) calculations, surface science studies, and reactor evaluations, Mo(2)C is
      identified as a highly selective HDO catalyst to selectively convert biomass
      derived oxygenates to unsaturated hydrocarbons through selective C-O bond
      scissions without C-C bond cleavage. This provides high-value HDO products for
      utilization as feedstocks for chemicals and fuels; this also reduces the overall
      consumption of H2 .

PMID- 23559532
TI  - Regulation of HA14-1 mediated oxidative stress, toxic response, and autophagy by
      curcumin to enhance apoptotic activity in human embryonic kidney cells.
AB  - An alteration in susceptibility to apoptosis not only contributes to promotion of
      malignancy but can also enhance drug resistance in response to anticancer
      therapies. HA14-1 is a small molecule which has the potential of inducing
      apoptosis in cancerous cells. HA14-1 manifests an antagonistic effect on
      antiapoptotic protein Bcl-2 and consequently induces cell death in various
      cancerous cell lines. However, it is also known to generate ROS and toxic
      response in the cells upon decomposition. Elevated level of ROS is responsible
      for oxidative stress and other pathological consequences, if not metabolized
      properly. The aim of the present study was to examine the synergistic effect of
      curcumin in promoting apoptosis by regulating the HA14-1 mediated ROS generation,
      toxicity, oxidative stress, and autophagy in human embryonic kidney cells. Our
      study demonstrates that curcumin efficiently scavenges HA14-1 mediated generation
      of ROS and toxic response resulting in augmentation of apoptosis in HEK 293T
      cells by promoting inhibition of antiapoptotic proteins and process of autophagy.
      Thus curcumin along with HA14-1 regulates cell proliferation by disruption of the
      antiapoptotic signaling mechanism. This approach could serve as a promising
      strategy for therapeutic potential to overcome their adverse effects.

PMID- 23559533
TI  - Factors affecting swallow outcome following treatment for advanced oral and
      oropharyngeal malignancies.
AB  - BACKGROUND: Treatment for tumors of the oral cavity and the oropharynx disrupts
      normal swallow function. The ability for oral diet postoperatively varies and may
      be influenced by surgery and patient-related factors. METHODS: In all, 114
      patients treated with surgery with and without chemoradiotherapy for advanced
      oral/oropharyngeal cancer were recruited. Clinicopathologic tumor parameters and
      reconstruction modalities were recorded. Swallow function was determined by oral
      intake, using the Functional Oral Intake Scale (FOIS) pretreatment and
      posttreatment. RESULTS: The median time to first attaining swallow function was
      14 days. Patients were less likely to attain tube independence within 1 year of
      surgery if they received radiotherapy or had a low FOIS score preoperatively.
      Patients' time to first attaining swallow function postsurgery was inversely
      related to the FOIS score presurgery. CONCLUSIONS: Swallow function recovery
      postsurgery is better in patients with higher FOIS presurgery, smaller tumors,
      and no requirement for radiotherapy.

PMID- 23559534
TI  - Student award winner in the Ph.D. category for the 2013 society for biomaterials
      annual meeting and exposition, april 10-13, 2013, Boston, Massachusetts :
      biomaterial-mediated cancer-specific DNA delivery to liver cell cultures using
      synthetic poly(beta-amino ester)s.
AB  - Liver cancer is a leading cause of cancer death. Most patients are treated by
      arterial injection of chemoembolizing agents, providing a convenient avenue for
      local treatment by novel therapies, including gene therapy. Poly(beta-amino
      ester)s (PBAEs) were synthesized and used to form nanoparticles for non-viral
      transfection of buffalo rat hepatoma (MCA-RH7777) and hepatocyte (BRL-3A) lines
      with eGFP and luciferase DNA. Hepatoma cells were transfected with up to (98 +/-
      0.4)% efficacy with no measurable cytotoxicity. Hepatocytes were transfected with
      as high as (73 +/- 0.4)% efficacy with (10 +/- 4)% non-specific cytotoxicity. In
      contrast, positive controls (branched polyethylenimine, LipofectamineTM 2000, and
      X-tremeGENE((r)) DNA HP) caused 30-90% toxicity in BRL-3A cells at doses required
      for >50% transfection. Of the 21 optimized PBAE-DNA formulations tested, 12
      showed significant specificity for hepatoma cells over hepatocytes in monoculture
      (p < 0.05 for both percentage transfected and eGFP expression intensity). Top
      polymers from eGFP studies also delivered luciferase DNA with 220 +/- 30-fold and
      470 +/- 30-fold greater specificity for hepatoma cells than hepatocytes.
      Transfections of co-cultures of hepatoma and hepatocytes with eGFP DNA also
      showed high specificity (1.9 +/- 0.1- to 5.8+/- 1.4-fold more transfected
      hepatoma cells than hepatocytes, measured by percentage transfected and flow
      cytometry). By eGFP intensity, up to 530 +/-60-fold higher average expression per
      cell was measured in hepatoma cells. One top formulation caused (95 +/- 0.2)%
      transfection in hepatoma cells and (27 +/- 0.2)% in hepatocytes [(96 +/- 9)%
      relative hepatocyte viability]. PBAE-based nanoparticles are a viable strategy
      for liver cancer treatment, delivering genes to nearly 100% of cancer cells while
      maintaining high biomaterial-mediated specificity to prevent toxic side-effects
      on healthy hepatocytes.

PMID- 23559535
TI  - Short-term comprehensive cardiac rehabilitation after AMI is associated with
      reduced 1-year mortality: results from the OMEGA study.
AB  - BACKGROUND: The prognostic effect of early, comprehensive short-term cardiac
      rehabilitation on top of current, guideline-adjusted treatment of acute
      myocardial infarction has not sufficiently been evaluated. DESIGN: Prospective
      cohort study. METHODS: Within the OMEGA study population, the clinical course of
      3560 patients still alive 3 months after acute myocardial infarction were
      evaluated by comparing patients who had attended to cardiac rehabilitation
      (70.6%) with those who did not. Total mortality and major adverse cerebrovascular
      and cardiovascular events, as well as non-fatal events, were evaluated within the
      time period of 4-12 months after hospital admission for acute myocardial
      infarction. The effect of cardiac rehabilitation on clinical events was estimated
      by using the propensity score method to adjust for confounding parameters in
      multivariate analysis. RESULTS: Patients participating in cardiac rehabilitation
      were younger, more often had acute revascularization, less often experienced non
      ST-elevation myocardial infarction, and less often had a history of diabetes or
      cardiovascular events. Total mortality (OR 0.46, 95% CI 0.27-0.77) and major
      adverse cerebrovascular and cardiovascular events (OR 0.53, 95% CI 0.38-0.75)
      were significantly lower in the rehabilitation group. Subgroup analysis including
      major clinical characteristics also revealed significantly reduced rates of total
      death and major adverse cerebrovascular and cardiovascular events in the
      rehabilitation group. CONCLUSIONS: Attendance to early, comprehensive short-term
      cardiac rehabilitation programmes on top of current guideline-adjusted treatment
      of acute myocardial infarction is associated with a significantly improved 1-year
      prognosis.

PMID- 23559537
TI  - Negative aspects of close social relations and 10-year incident ischaemic heart
      disease hospitalization among middle-aged Danes.
AB  - BACKGROUND: Little is known about the association between negative aspects of
      close social relations and development of ischaemic heart disease (IHD). We aim
      to address if the experience of worries/demands and conflicts with close social
      relations are related to risk of first-time hospitalization with IHD and whether
      emotional support can buffer this effect. METHODS: A total of 8550 randomly
      selected men and women aged 36-52 years free of earlier IHD hospitalization at
      baseline in 2000 were followed prospectively for first-time hospitalization with
      IHD (ICD10: I21-25) through 2010 in the Danish National Patient Registry. Cox
      regression analysis was used to analyse data and all analyses were adjusted for
      age, gender, social class, cohabitation, and depressive symptoms. RESULTS:
      Worries/demands from and conflicts with children were associated with IHD
      hospitalization in an exposure-dependent manner (p-trends 0.0001 and 0.03) with
      twice the risk among those most highly exposed, HRworries/demands = 2.05 (95% CI
      0.91-4.54) and HRconflicts=1.90 (95% CI 1.00-3.61). 'Always' experiencing
      worries/demands from partner was also associated with a nearly twice the risk of
      IHD, whereas no association was found for conflicts with partner. High levels of
      worries/demands from or conflicts with family and friends were associated with a
      40% higher risk of IHD. CONCLUSIONS: Negative aspects of close social relations
      are associated with higher risk of incident IHD hospitalization except for
      conflicts with partner. We found no clear evidence of a buffering effect of
      emotional support.

PMID- 23559536
TI  - The association of maternal prenatal psychosocial stress with vascular function
      in the child at age 10-11 years: findings from the Avon longitudinal study of
      parents and children.
AB  - OBJECTIVE: To investigate whether (1) maternal psychosocial stress
      (depression/anxiety) during pregnancy is associated with offspring vascular
      function and (2) whether any association differs depending on the gestational
      timing of exposure to stress. We also investigated whether any association is
      likely to be due to intrauterine mechanisms by (3) comparing with the association
      of paternal stress with offspring vascular function and (4) examining whether any
      prenatal association is explained by maternal postnatal stress. METHODS AND
      RESULTS: Associations were examined in a UK birth cohort, with offspring outcomes
      (systolic and diastolic blood pressure, SBP and DBP, endothelial function
      assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness
      assessed by carotid to radial pulse wave velocity (PWV), brachial artery
      distensibility (DC), and brachial artery diameter (BD) assessed at age 10-11
      years (n = 4,318). Maternal depressive symptoms and anxiety were assessed at 18
      and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed
      at week 19. With the exception of DBP and BD, there were no associations of
      maternal depressive symptoms with any of the vascular outcomes. Maternal
      depressive and anxiety symptoms were associated with lower offspring DBP and
      wider BD, though the latter attenuated to the null with adjustment for
      confounding factors. Paternal symptoms were not associated with offspring
      outcomes. Maternal postnatal depressive symptoms were associated with lower
      offspring SBP. CONCLUSIONS: We found no evidence to support the hypothesis that
      maternal stress during pregnancy adversely affects offspring vascular function at
      age 10-12 years via intrauterine mechanisms.

PMID- 23559538
TI  - Estimating salt intake in a Caucasian population: can spot urine substitute 24
      hour urine samples?
AB  - BACKGROUND: A simple and valid alternative for 24-hour urine collection to
      estimate populational 24-hour urinary sodium excretion would be desirable for
      monitoring sodium intake in populations. AIM: To assess the validity of the
      predicted 24-hour urinary sodium excretion using spot urine and two different
      prediction methods in a Danish population. METHODS: Overall, 473 Danish
      individuals provided a para-aminobenzoic acid-validated complete 24-hour urine
      collection and a spot urine sample. Data were collected in the DanThyr study (248
      women aged 25-30 years and 60-65 years) and the Inter99 study (102 men and 113
      women aged 30-60 years), respectively. The measured 24-hour urine sodium
      excretion was compared with the predicted 24-hour sodium excretion from a causal
      urine specimen, using both the Tanaka prediction method and a prediction model
      developed in a Danish population. RESULTS: The measured 24-hour sodium excretion
      (median, 5th to 95th percentile) was men 195 (110 to 360) and women 139 (61 to
      258), whereas the predicted 24-hour sodium excretion for the Tanaka model was men
      171 (117 to 222) and women 153 (92 to 228) and for the Danish model was men 207
      (146 to 258); women 134 (103 to 163). The Spearman correlation between predicted
      and measured 24-hour sodium excretion was 0.39 and 0.49 for the Tanaka and the
      Danish model, respectively. For both prediction models, the proportion of
      individuals classified in the same or adjacent quintile was 74% for men and 64%
      for women. CONCLUSIONS: Both prediction models gave a reasonable classification
      of individuals according to their sodium excretion. However, the median daily
      sodium intake was estimated more precisely by the Danish model, especially among
      men.

PMID- 23559539
TI  - AMPK synergizes with the combined treatment of 1'-acetoxychavicol acetate and
      sodium butyrate to upregulate phase II detoxifying enzyme activities.
AB  - SCOPE: Phase II enzymes play important roles in detoxifying xenobiotics. We
      previously reported that both 1'-acetoxychavicol acetate (ACA) and sodium
      butyrate individually increased phase II enzyme activities. Here, we determined
      the combined action of ACA and sodium butyrate on phase II enzyme activities in
      intestinal epithelial cells (IEC 6). METHODS AND RESULTS: ACA and sodium butyrate
      synergistically increased phase II enzyme activities. Protein levels of
      intranuclear transcription factor NF-E2-related factor 2 (Nrf2) were increased by
      ACA or sodium butyrate treatment, but treatment with both did not produce a
      synergistic effect. Intranuclear p53 protein levels were increased by ACA but
      decreased by sodium butyrate alone or combined treatment with ACA and sodium
      butyrate. In contrast, p53 acetylation was promoted by sodium butyrate and the
      ACA and sodium butyrate combination. Inhibition of AMPK activity decreased phase
      II enzyme activities that were upregulated by treatment with ACA plus sodium
      butyrate or other phytochemicals, including kaempferol, quercetin, and
      epigallocatechin-3-gallate. Combined treatment with ACA and sodium butyrate
      increased phosphorylated AMPK levels. CONCLUSION: These results suggest that ACA
      and sodium butyrate synergistically contribute to xenobiotics metabolism. The
      combined ACA and sodium butyrate treatment synergistically upregulated phase II
      enzyme activities through AMPK activation and p53 acetylation.

PMID- 23559540
TI  - High use of health services in patients with suboptimal asthma drug regimens: a
      population-based assessment in British Columbia, Canada.
AB  - BACKGROUND: Despite numerous clinical guidelines on asthma management, patients
      often receive suboptimal drug therapy. This study identified patients who
      received suboptimal regimens according to the National Heart, Lung and Blood
      Institute (NHLBI) Guidelines for the Diagnosis and Management of Asthma in a
      complete population (residents of British Columbia, Canada) and determined the
      association between patients' regimens and utilization of healthcare services.
      METHODS: A total of 65,345 asthma patients were identified using provincial
      health service utilization data (including all respiratory-related prescription
      medication dispensings, physician and hospital visits) for the 2009 fiscal year.
      Patient-specific regimens of inhaled short-acting bronchodilators (SABA) with or
      without inhaled corticosteroids (ICS) were categorized as optimal or suboptimal.
      Logistic regression models were used to determine the association between regimen
      optimality and health service utilization, adjusted for socioeconomic status,
      prior year hospital and emergency department (ED) visits for asthma. RESULTS:
      Patients with suboptimal regimens had significantly greater risk of using health
      services than patients with optimal regimens of SABA and/or ICS. In particular,
      adolescents with suboptimal regimens were the most likely to have hospital
      admissions (odds ratio (OR) 3.8; 95% confidence interval (CI) 1.8-7.8), visit the
      ED (OR 2.2; 95% CI 1.6-3.1) and be high users of family physician services (OR
      5.7; 95% CI 4.0-8.1) compared with patients in other age groups. CONCLUSIONS:
      Suboptimal regimens are associated with significantly high usage of health
      services. Identifying patients with suboptimal regimens and improving their
      medication management in accordance with asthma clinical guidelines are likely to
      result in lower health service utilization.

PMID- 23559541
TI  - Adverse analytical findings with clenbuterol among U-17 soccer players attributed
      to food contamination issues.
AB  - The illicit use of growth promoters in animal husbandry has frequently been
      reported in the past. Among the drugs misused to illegally increase the benefit
      of stock farming, clenbuterol has held a unique position due to the substance's
      composition, mechanism of action, metabolism, and disposition. Particularly
      clenbuterol's disposition in animals' edible tissues destined for food production
      can cause considerable issues on consumption by elite athletes registered in
      national and international doping control systems as demonstrated in this case
      related study. Triggered by five adverse analytical findings with clenbuterol
      among the Mexican national soccer team in out-of-competition controls in May
      2011, the Federation Internationale de Football Association (FIFA) initiated an
      inquest into a potential food contamination (and thus sports drug testing)
      problem in Mexico, the host country of the FIFA U-17 World Cup 2011. Besides 208
      regular doping control samples, which were subjected to highly sensitive mass
      spectrometric test methods for anabolic agents, 47 meat samples were collected in
      team hotels during the period of the tournament and forwarded to Institute of
      Food Safety, RIKILT. In 14 out of 47 meat samples (30%), clenbuterol was detected
      at concentrations between 0.06 and 11 ug/kg. A total of 109 urine samples out of
      208 doping control specimens (52%) yielded clenbuterol findings at concentrations
      ranging from 1-1556 pg/ml, and only 5 out of 24 teams provided urine samples that
      did not contain clenbuterol. At least one of these teams was on a strict 'no
      meat' diet reportedly due to the known issue of clenbuterol contamination in
      Mexico. Eventually, owing to the extensive evidence indicating meat contamination
      as the most plausible reason for the extraordinary high prevalence of clenbuterol
      findings, none of the soccer players were sanctioned. However, elite athletes
      have to face severe consequences when testing positive for a prohibited anabolic
      agent and sufficient supporting information corroborating the scenario of
      inadvertent ingestion are required to be acquitted from anti-doping rule
      violations. Hence, governmental contribution is urgently needed to combat the
      illegal use of clenbuterol in stock breading.

PMID- 23559542
TI  - Novel insight into the biological functions of syndecan ectodomain core proteins.
AB  - Syndecans are a four member family of multifunctional transmembrane heparan
      sulphate bearing cell surface receptors. Each family member has common molecular
      architecture but a distinct expression profile. Numerous molecular interactions
      between syndecan heparan sulphate chains, growth factors, cytokines, and
      extracellular matrix molecules have been reported and syndecans are intimately
      associated with cell adhesion and migration. Here, we describe the important
      emerging concept that contained within syndecan extracellular core proteins are
      "adhesion regulatory domains." Cell adhesion is driven by the integrins and
      syndecan ectodomain adhesion regulatory domains can alter integrin driven
      cellular responses. Cell adhesion and migration is central to numerous
      pathologies and an understanding of how syndecan ectodomains influence integrins
      will lead to novel therapeutic strategies.

PMID- 23559543
TI  - Nutritional status, food intake, and dysphagia in long-term survivors with head
      and neck cancer treated with chemoradiotherapy: a cross-sectional study.
AB  - BACKGROUND: The aim of this study was to evaluate nutritional status, food
      intake, and dysphagia in long-term head and neck cancer survivors. METHODS:
      Thirty-two patients with stage III-IV head and neck cancer treated by
      chemoradiotherapy were invited to evaluate nutritional status (malnutrition,
      relative weight loss), food intake (food modification; quality), and dysphagia.
      RESULTS: At a median follow up of 44 months, 6 of 32 patients were at risk for
      malnutrition. Women (p = .049) and patients with high body mass index before
      treatment (p = .024) showed more weight loss. None of the 32 patients could eat a
      "full diet." Six patients used nutritional supplements/tube feeding. Low
      dysphagia-related quality of life scores were significantly correlated to
      increased food modification (r = 0.405; p = .024). CONCLUSIONS: Nutritional
      advice in patients with head and neck cancer is still necessary years after
      chemoradiation and should focus on nutritional status, food modification, and
      quality, in accord with recommended food groups.

PMID- 23559544
TI  - Re: Proton vs intensity-modulated radiotherapy for prostate cancer: patterns of
      care and early toxicity.

PMID- 23559545
TI  - Impact of the biophysical features of a 3D gelatin microenvironment on
      glioblastoma malignancy.
AB  - Three-dimensional tissue engineered constructs provide a platform to examine how
      the local extracellular matrix (ECM) contributes to the malignancy of cancers
      such as human glioblastoma multiforme. Improved resolution of how local matrix
      biophysical features impact glioma proliferation, genomic and signal transduction
      paths, as well as phenotypic malignancy markers would complement recent
      improvements in our understanding of molecular mechanisms associated with
      enhanced malignancy. Here, we report the use of a gelatin methacrylate (GelMA)
      platform to create libraries of three-dimensional biomaterials to identify
      combinations of biophysical features that promote malignant phenotypes of human
      U87MG glioma cells. We noted key biophysical properties, namely matrix density,
      crosslinking density, and biodegradability, that significantly impact glioma cell
      morphology, proliferation, and motility. Gene expression profiles and secreted
      markers of increased malignancy, notably VEGF, MMP-2, MMP-9, HIF-1, and the ECM
      protein fibronectin, were also significantly impacted by the local biophysical
      environment as well as matrix-induced deficits in diffusion-mediated oxygen and
      nutrient biotransport. Overall, this biomaterial system provides a flexible
      platform to explore the role biophysical factors play in the etiology, growth,
      and subsequent invasive spreading of gliomas.

PMID- 23559546
TI  - Isotachophoresis with counterflow in an open capillary: computer simulation and
      experimental validation.
AB  - The purpose of applying a countercurrent flow to isotachophoretic migration is to
      increase the effective separation channel length during ITP. However, severe
      dispersion induced by applying a counterflow can be detrimental to ITP. This
      paper uses numerical simulations in a 2D axisymmetric domain to investigate the
      dispersion caused by a parabolic counterflow in open-capillary ITP. Counterflow
      in these simulations was generated by applying a back pressure to stop the
      isotachophoretic stack, i.e., forming stationary ITP zones. It is found that
      dispersion is strongly related to analyte molecular diffusivity: R-phycoerythrin,
      due to its small diffusivity, showed ~20-fold increase in zone width in
      stationary counterflow ITP, compared to ITP in the absence of counterflow, while
      fluorescein only had ~10% increase in zone width under similar operating
      conditions. Applying the Taylor-Aris dispersion formula in counterflow ITP
      simulations provided only a rough estimate of the dispersion, e.g.,
      overestimation of analyte zone widths. Experiments on counterflow ITP were
      conducted in a silica capillary that was covalently and dynamically coated to
      exclude electroosmosis effect. The counterflow was generated by adjusting the
      relative height of the fluids in the two reservoirs at the capillary ends. Good
      qualitative agreement between simulations and experiments was found.

PMID- 23559547
TI  - Relationship between postoperative complications and survival after free flap
      reconstruction for oral cavity squamous cell carcinoma.
AB  - BACKGROUND: Current literature on the effect of postoperative complications on
      survival outcomes in head and neck cancers remains contradictory. This study
      assesses whether postoperative complications adversely affect survival in cases
      of complex surgical ablation and reconstruction of oral squamous cell carcinoma.
      METHODS: In all, 255 consecutive patients with complete clinicopathologic data
      were included. Survival was determined using the log-rank test and Kaplan-Meier
      survival curves were generated. A Cox proportional hazards model was used to
      adjust for the effect of other significant covariates to determine the
      independent effect of complication variables for overall survival (OS). A
      competing risk model was used for disease-specific survival (DSS). RESULTS: On
      multivariable analysis, major complications independently prognosticated for
      reduced OS [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1-3.2, p =
      .02]. There was no evidence for an association between any complication-variable
      and DSS or recurrence. CONCLUSIONS: Major postoperative complications are
      independently associated with decreased OS.

PMID- 23559548
TI  - Cell biological responses of osteoblasts on anodized nanotubular surface of a
      titanium-zirconium alloy.
AB  - Anodization of titanium and its alloys, under controlled conditions, generates a
      nanotubular architecture on the material surface. The biological consequences of
      such changes are poorly understood, and therefore, we have analyzed the cellular
      and molecular responses of osteoblasts that were plated on nanotubular anodized
      surface of a titanium-zirconium (TiZr) alloy. Upon comparing these results with
      those obtained on acid etched and polished surfaces of the same alloy, we
      observed a significant increase in adhesion and proliferation of cells on
      anodized surfaces as compared to acid etched or polished surface. The expression
      of genes related to cell adhesion was high only on anodized TiZr, but that of
      genes related to osteoblast differentiation and osteocalcin protein and
      extracellular matrix secretion were higher on both anodized and acid etched
      surfaces. Examination of surface morphology, topography, roughness, surface area
      and wettability using scanning electron microscopy, atomic force microscopy, and
      contact angle goniometry, showed that higher surface area, hydrophilicity, and
      nanoscale roughness of nanotubular TiZr surfaces, which were generated
      specifically by the anodization process, could strongly enhance the adhesion and
      proliferation of osteoblasts. We propose that biological properties of known
      bioactive titanium alloys can be further enhanced by generating nanotubular
      surfaces using anodization.

PMID- 23559549
TI  - The role of natural killer cells in hepatitis C infection.
AB  - HCV infection is an exponentially growing health burden worldwide, with an
      estimated 170 million people infected. Although therapies for HCV are continually
      improving, there remain a considerable proportion of patients who do not achieve
      viral eradication and develop liver disease. Natural killer (NK) cells are
      crucial for T-cell activation and are one of the first-line sentinel cell
      responders to viral infection. A recent explosion in studies exploring the role
      of NK cells in HCV infection has yielded important mechanistic information and
      intriguing potential therapeutic options for HCV infection. This review provides
      a general overview of normal NK cell function and outlines some of the important
      mechanisms characterizing the immune interplay between NK cells and HCV
      infection. 

PMID- 23559550
TI  - Amide proton transfer imaging of the human breast at 7T: development and
      reproducibility.
AB  - Chemical exchange saturation transfer (CEST) can offer information about protons
      associated with mobile proteins through the amide proton transfer (APT) effect,
      which has been shown to discriminate tumor from healthy tissue and, more
      recently, has been suggested as a prognosticator of response to therapy. Despite
      this promise, APT effects are small (only a few percent of the total signal), and
      APT imaging is often prone to artifacts resulting from system instability. Here
      we present a procedure that enables the detection of APT effects in the human
      breast at 7T while mitigating these issues. Adequate signal-to-noise ratio (SNR)
      was achieved via an optimized quadrature RF breast coil and 3D acquisitions. To
      reduce the influence of fat, effective fat suppression schemes were developed
      that did not degrade SNR. To reduce the levels of ghosting artifacts, dummy scans
      have been integrated into the scanning protocol. Compared with results obtained
      at 3T, the standard deviation of the measured APT effect was reduced by a factor
      of four at 7T, allowing for the detection of APT effects with a standard
      deviation of 1% in the human breast at 7T. Together, these results demonstrate
      that the APT effect can be reliably detected in the healthy human breast with a
      high level of precision at 7T.

PMID- 23559551
TI  - Lagrangian analysis of hemodynamics data from FSI simulation.
AB  - We present the computation of lagrangian-based flow characterization measures for
      time-dependent, deformable-wall, finite-element blood flow simulations.
      Applicability of the algorithm is demonstrated in a fluid-structure interaction
      simulation of blood flow through a total cavopulmonary connection (Fontan
      procedure), and results are compared with a rigid-vessel simulation.
      Specifically, we report on several important lagrangian-based measures including
      flow distributions, finite-time Lyapunov exponent fields, particle residence
      time, and exposure time calculations. Overall, strong similarity in lagrangian
      measures of the flow between deformable and rigid-vessel models was observed.

PMID- 23559553
TI  - The tool better honed: Modern cytometric approach to protein phosphorylation.

PMID- 23559552
TI  - A morpholino-based screen to identify novel genes involved in craniofacial
      morphogenesis.
AB  - BACKGROUND: The regulatory mechanisms underpinning facial development are
      conserved between diverse species. Therefore, results from model systems provide
      insight into the genetic causes of human craniofacial defects. Previously, we
      generated a comprehensive dataset examining gene expression during development
      and fusion of the mouse facial prominences. Here, we used this resource to
      identify genes that have dynamic expression patterns in the facial prominences,
      but for which only limited information exists concerning developmental function.
      RESULTS: This set of ~80 genes was used for a high-throughput functional analysis
      in the zebrafish system using Morpholino gene knockdown technology. This screen
      revealed three classes of cranial cartilage phenotypes depending upon whether
      knockdown of the gene affected the neurocranium, viscerocranium, or both. The
      targeted genes that produced consistent phenotypes encoded proteins linked to
      transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1,
      wu:fb16h09), and extracellular matrix function (smoc2). The majority of these
      phenotypes were not altered by reduction of p53 levels, demonstrating that both
      p53-dependent and -independent mechanisms were involved in the craniofacial
      abnormalities. CONCLUSIONS: This Morpholino-based screen highlights new genes
      involved in development of the zebrafish craniofacial skeleton with wider
      relevance to formation of the face in other species, particularly mouse and
      human.

PMID- 23559554
TI  - Simultaneous separation of water- and fat-soluble vitamins in isocratic pressure
      assisted capillary electrochromatography using a methacrylate-based monolithic
      column.
AB  - A method of simultaneous separation of water- and fat-soluble vitamins using
      pressure-assisted CEC with a methacrylate-based capillary monolithic column was
      developed. In the proposed method, water-soluble vitamins were mainly separated
      electrophoretically, while fat soluble-ones were separated chromatographically by
      the interaction with a methacrylate-based monolith. A mixture of six water
      soluble and four fat-soluble vitamins was separated simultaneously within 20 min
      with an isocratic elution using 1 M formic acid (pH 1.9)/acetonitrile (30:70,
      v/v) containing 10 mM ammonium formate as a mobile phase. When the method was
      applied to a commercial multivitamin tablet and a spiked one, the vitamins were
      successfully analyzed, and no influence of the matrix contained in the tablet was
      observed.

PMID- 23559555
TI  - Neck spasm after chemoradiotherapy for head and neck cancer: natural history and
      dosimetric correlates.
AB  - BACKGROUND: Little is known about the determinants of postradiation neck spasms
      in patients with head and neck cancer. METHODS: Patients with head and neck
      cancer treated with radiation therapy (RT) from 2004 to 2010 who experienced neck
      spasms werereviewed. Radiation doses were generated for their sternocleidomastoid
      (SCM) muscles bilaterally. Unaffected SCMs were used as controls. RESULTS: Thirty
      four patients reported neck spasms. Thirty had received definitive
      chemoradiation, and 4 had RT alone. Seven also had an ipsilateral neck
      dissection. Median time to onset was 23 months (range, 6-67 months). There were
      significantly higher radiation doses to the affected SCMs with a median of the
      mean dose to the affected and unaffected SCM of 62.3 Gy (range, 29-71 Gy) and
      53.7 Gy (range, 27-65 Gy), respectively (p < .0001). Other dosimetric variables
      were also statistically significant but were highly correlated with the mean SCM
      dose. Neck dissection did not affect our results. CONCLUSION: Neck spasms after
      chemotherapy intensity-modulated radiation therapy (IMRT) shows a strong dose
      response relationship.

PMID- 23559556
TI  - Introduction: review series--palliative medicine.

PMID- 23559557
TI  - Palliative care for dementia--time to think again?
AB  - It is estimated that there are 35.6 million people with dementia worldwide and
      this is projected to increase to over 115 million by the year 2050. Dementia is a
      progressive neurodegenerative disease that significantly reduces survival. End-of
      life care received by this group is often poor and does not equate to that
      offered in other life limiting illnesses. This review highlights results from a
      large UK study of informal carers of people with dementia to explore what are
      determinants of care for people with dementia and their family carers. New
      perspectives as to models of care for end-of-life care for patients with dementia
      are discussed together with how these may be implemented and delivered within
      wider community settings and contexts, where many people with dementia may be
      cared for in the future.

PMID- 23559558
TI  - Relationship of a turbidity of an oral rinse with oral health and malodor in
      Vietnamese patients.
AB  - AIM: In the present study, the relationship between the turbidity of mouth-rinse
      water and oral health conditions, including oral malodor, in patients with (n =
      148) and without (n = 231) periodontitis was examined. METHODS: The turbidity of
      20 mL distilled water that the patients rinsed in their mouths 10 times was
      measured using a turbidimeter. Oral malodor was evaluated using an organoleptic
      test and Oral Chroma. Oral health conditions, including decayed teeth,
      periodontal status, oral hygiene status, proteolytic activity of the N-benzoyl-dl
      arginine-2-napthilamide (BANA) test on the tongue coating, and salivary flow
      rate, were assessed. RESULTS: Turbidity showed significant correlations with oral
      malodor and all oral health parameters in the periodontitis group. In the non
      periodontitis group, turbidity showed significant correlations with oral malodor
      and oral health parameters, including dental plaque, tongue coating, BANA test,
      and salivary flow rate. The regression analysis indicated that turbidity was
      significantly associated with methyl mercaptan and the BANA test in the
      periodontitis group, and with hydrogen sulfide, dental plaque, tongue coating,
      and salivary flow rate in the non-periodontitis group. CONCLUSION: The findings
      of the present study indicate that the turbidity of mouth-rinse water could be
      used as an indicator of oral health conditions, including oral malodor.

PMID- 23559559
TI  - Preserving participant anonymity during remote preenrollment consent form
      checking.
AB  - BACKGROUND: In biomedical research, the consent form must comply with regulatory
      requirements. Checking for compliance typically has been performed on-site and
      most frequently after a participant's final enrollment. We use a procedure for
      remote preenrollment checking of consent forms that protects participant
      identities. This procedure requires a copy of the consent form that partially
      masks the fields for participant's name and signature; this copy is faxed to the
      clinical trials unit for checking. PURPOSE: To describe our efforts to identify
      an appropriate printed masking pattern. We tried several patterns that permit
      ascertainment of the presence of signatures and names and evaluated each one with
      respect to degree of masking participant identities. METHODS: We assessed the
      efficiency of a satisfactory pattern through an experiment. We created forms with
      variants of the masking pattern on the copy to be faxed. We completed the forms
      with fictitious identities before copies were faxed and checked by clinical
      research associates. We measured the rate of empty and filled fields detected and
      the rate of letters and names correctly read. The target was defined as 100% for
      the rate of empty and filled fields detected and 0% for the rate of letters and
      names correctly read. RESULTS: The best masking pattern allowed the detection of
      100% empty and filled fields and the reading of 0% names and 19% letters.
      Consequently, the consent form with the selected masking pattern has been used
      routinely in our clinical trials unit. LIMITATIONS: We tested only five
      fictitious identities, five individuals who completed forms, and three who
      checked forms. Also, we initially considered only four patterns and variations in
      them. CONCLUSIONS: We defined a masking pattern that satisfactorily fulfilled our
      needs for confidentiality. This and other procedures for remote preenrollment
      checking of consent form can be a key component of a risk-based monitoring
      strategy.

PMID- 23559560
TI  - Structural characterization of Staphylococcus aureus biotin protein ligase and
      interaction partners: an antibiotic target.
AB  - The essential metabolic enzyme biotin protein ligase (BPL) is a potential target
      for the development of new antibiotics required to combat drug-resistant
      pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein,
      possessing both biotin ligase and transcription repressor activities. This
      positions BPL as a key regulator of several important metabolic pathways. Here,
      we report the structural analysis of both holo- and apo-forms of SaBPL using X
      ray crystallography. We also present small-angle X-ray scattering data of SaBPL
      in complex with its biotin-carboxyl carrier protein substrate as well as the
      SaBPL:DNA complex that underlies repression. This has revealed the molecular
      basis of ligand (biotinyl-5'-AMP) binding and conformational changes associated
      with catalysis and repressor function. These data provide new information to
      better understand the bifunctional activities of SaBPL and to inform future
      strategies for antibiotic discovery.

PMID- 23559561
TI  - Rapid isolation of omega-3 long-chain polyunsaturated fatty acids using
      monolithic high performance liquid chromatography columns.
AB  - Eicosapentaenoic and docosahexaenoic acids are important bio-active fatty acids
      in fish oils. Monolithic HPLC columns both in the polymeric cation exchange
      (silver-ion) and RP formats were compared with corresponding packed columns for
      the isolation of these acids from tuna oil ethyl esters. Monolithic columns in
      both formats enabled rapid (typically 5-10 min) separations compared with packed
      columns (30 min). Polymeric monolithic silver-ion disc column rapidly furnished
      mixtures of eicosapentaenoic and docosahexaenoic esters (90% purity) within 5-10
      min, but was unable to resolve individual esters. A preparative version of the
      same column (80 mL bed volume) enabled isolation (>88% purity) of 100 mg
      quantities of eicosapentaenoic and docosahexaenoic esters from esterified tuna
      oil within 6 min. Baseline separation of eicosapentaenoic and docosahexaenoic
      esters was achieved on all RP columns. The results show that there is potential
      to use polymeric monolithic cation exchange columns for scaled-up preparation of
      eicosapentaenoic and docosahexaenoic ester concentrates from fish oils.

PMID- 23559562
TI  - The transcription factor Sry-related HMG box-4 (SOX4) is required for normal
      renal development in vivo.
AB  - BACKGROUND: The DNA-binding transcription factor Wilms' Tumor Suppressor-1 (WT1)
      plays an essential role in nephron progenitor differentiation during renal
      development. We previously used Wt1 chromatin-immunoprecipitation coupled to
      microarray (ChIP-chip) to identify novel Wt1 target genes that may regulate
      nephrogenesis in vivo. We discovered that all three members of the SoxC
      subfamily, namely, Sox4, Sox11, and Sox12, are bound by Wt1 in mouse embryonic
      kidneys in vivo. SoxC genes play master roles in determining neuronal and
      mesenchymal progenitor cell fate in a multitude of developmental processes, but
      their function in the developing kidney is largely unknown. RESULTS: Here we show
      that all three SoxC genes are expressed in the nephrogenic lineages during renal
      development. Conditional ablation of Sox4 in nephron progenitors and their
      cellular descendants (Sox4(nephron-) mice) results in a significant reduction in
      nephron endowment. By postnatal day (P)7, Sox4(nephron-) renal corpuscles exhibit
      reduced numbers of Wt1+ podocytes together with loss of expression of the slit
      diaphragm protein nephrin. Sox4(nephron-) mice develop early-onset proteinacious
      glomerular injury within 2 weeks of birth progressing to end-stage renal failure
      within 5-9 months. CONCLUSIONS: Collectively, our results demonstrate an
      essential requirement of Sox4 for normal renal development in vivo.

PMID- 23559563
TI  - A sensitive tool to measure CFTR channel activity.

PMID- 23559564
TI  - Longitudinal study on the correlations of thyroid antibody and thyroid hormone
      levels after radiotherapy in patients with nasopharyngeal carcinoma with
      radiation-induced hypothyroidism.
AB  - BACKGROUND: The purpose of this study was to evaluate the correlations of thyroid
      antibody and thyroid hormone in postradiotherapy (post-RT) patients with
      nasopharyngeal carcinoma (NPC). METHODS: Serum thyroid-stimulating hormone (TSH),
      free triiodothyronine (fT3), free thyroxine (fT4), thyroperoxidase antibody (anti
      TPO), and thyroglobulin antibody (anti-TG) levels of 55 patients with NPC were
      taken before RT and at 3, 6, 12, and 18 months after RT. Patients with
      hypothyroidism at 18 months after RT and those with normal thyroid function were
      categorized into the hypo and normal groups, respectively. The thyroid antibody
      levels were compared between the 2 groups, and the correlations of thyroid
      antibody and thyroid hormone were evaluated for the hypo group. RESULTS: The anti
      TPO and anti-TG of the hypo group were higher than the normal group. In the hypo
      group, there was a positive correlation (r = 0.51) between TSH and anti-TG and a
      negative correlation between fT4 and anti-TPO (r = -0.55). CONCLUSION: There were
      correlations of the thyroid antibody and thyroid hormone levels in patients with
      radiation-induced hypothyroidism.

PMID- 23559565
TI  - Antimicrobial effects of calcium hydroxide, chlorhexidine, and propolis on
      Enterococcus faecalis and Candida albicans.
AB  - AIM: To evaluate the efficacy of calcium hydroxide (Ca[OH]2 ), 2% chlorhexidine
      (CHX) gel, and propolis against both Enterococcus faecalis (E. faecalis) and
      Candida albicans (C. albicans) using infected dentine models at two different
      depths (100 and 200 MUm) after 14 days of application. METHODS: A total of 120
      roots of extracted single-rooted human teeth were chemo-mechanically prepared and
      sterilized. Sixty roots were infected with E. faecalis, and the remaining 60 with
      C. albicans. Each group was divided into four subgroups (n = 15) to apply
      intracanal medicaments, namely saline solution (negative control), Ca(OH)2 , CHX,
      and propolis during the 14 days. Dentine shavings were collected and cultivated.
      Colony-forming units (c.f.u.) were registered. Statistical analysis was done
      using the Kruskal-Wallis test, followed by Dunn's/Bonferroni multiple comparison
      test (P < 0.05). RESULTS: All experimental agents significantly reduced E.
      faecalis c.f.u. There was no significant difference between CHX and propolis
      reducing E. faecalis c.f.u. at 100 and 200 MUm. Only CHX had a statistically
      significant antifungal efficacy in the C. albicans group at the two depths
      assessed. CHX was the most potent medicament against both E. faecalis and C.
      albicans, and Ca(OH)2 was the least. CONCLUSION: Both CHX and propolis were the
      most effective against E. faecalis, whereas only CHX had the highest antifungal
      activity on C. albicans in dentine of extracted teeth.

PMID- 23559566
TI  - Surface properties and wear performances of siloxane-hydrogel contact lenses.
AB  - The low surface roughness of disposable contact lenses made of a new siloxane
      hydrogel loaded with hyaluronic acid is reported, as studied by atomic force
      microscopy (AFM). Before the wear, the surface is characterized by out-of-plane
      and sharp structures, with maximum height of about 10 nm. After a wear of 8 h,
      evidence of two typical morphologies is provided and discussed. One morphology
      (sharp type) has a similar aspect as the unworn lenses with a slight increase in
      both the height and the number of the sharp peaks. The other morphology (smooth
      type) is characterized by troughs and bumpy structures. Wettability and clinical
      performances are also discussed, the latter deduced by the ocular-surface-disease
      index (OSDI). The main finding arising from this work is the indication of
      correlation between the change of the OSDI before and after wear and the lens
      surface characteristics obtained by AFM.

PMID- 23559567
TI  - Validation of novel reference genes for RT-qPCR studies of gene expression in
      Xenopus tropicalis during embryonic and post-embryonic development.
AB  - BACKGROUND: Accurate interpretation of transcriptome profiling by quantitative
      PCR requires the establishment of species-specific standards. However, the
      selection of reference genes for assessing RNA expression profiles in Xenopus
      laevis and Xenopus tropicalis was mostly based on historical reasons and they
      often only reflect the traditions of a laboratory. RESULTS: We investigated the
      expression stability of 10 genes (dicer1, drosha, eef1a1, elavl3, gsc, h4, odc1,
      rpl8, smn2, tbp), 8 of which are commonly used as internal controls in published
      RT-qPCR experiments. We defined specific primer pairs and evaluated their
      suitability as reference genes by performing RT-qPCR expression profiling in
      Xenopus tropicalis. Gene expression stability was assayed in a set of 15
      developmental stages from the egg to the froglet, and in dissected embryos.
      CONCLUSIONS: Overall, we determined a set of qualified reference genes for
      distinct developmental periods. We recommend the use of dicer1, drosha, eef1a1,
      and smn2 from early embryonic development up to the end of metamorphosis. During
      early embryogenesis drosha, eef1a1, smn2 are suitable. For the whole post
      embryonic development and for metamorphic stages including pro-metamorphosis and
      metamorphic climax, we recommend the use of drosha and smn2. These reference
      genes should prove their usefulness for data comparison across studies.

PMID- 23559568
TI  - Sustaining international partnerships: the European Master of Science Programme
      in Occupational Therapy, a case study.
AB  - International partnerships are a mechanism for supporting the academic
      development of occupational therapy and promoting cultural competence. This case
      study describes the factors that have helped to sustain a post-qualifying
      programme implemented by five higher education institutions in Denmark, the
      Netherlands, Sweden, Switzerland and the UK since 1999. Data collection methods
      were documentary analysis and the reflections of a purposive sample of six key
      informants. Cohort and outcome data, from 193 students from 31 countries who
      enrolled between 1999 and 2011, are reported. Each cohort comprises students from
      an average of eight countries to optimize inter-cultural dialogue. Four factors
      support sustainability. These are 1) supportive professional European networks;
      2) timeliness and alignment with European higher education policy; 3) partnership
      structures and processes that emphasize joint decision making and accountability;
      and 4) the stimulus and satisfaction associated with internationalization. The
      main limitations are considering the OT-EuroMaster as an intrinsic case study and
      using opportunistic data collection that undermines the rigor and transferability
      of the findings. Future opportunities include doctoral networks, transnational
      research and sharing our curricula design with other Regions to spread the
      collaborative, capacity building endeavours more widely.

PMID- 23559569
TI  - The apparent paradox of maternal seropositivity as a risk factor for congenital
      cytomegalovirus infection: a population-based prediction model.
AB  - Because maternal seropositivity for CMV is associated with substantial protection
      against congenital CMV infection, prevention measures have focused mainly on
      seronegative pregnant women for decades. However, population-wide insight in the
      contribution of nonprimary infection (reactivation and/or re-infection with a
      different strain) on the most common sequela, hearing loss, is missing. A
      population-based prediction model was developed to estimate the proportion of
      congenital CMV-related hearing loss resulting from nonprimary maternal infection.
      Incorporated was a meta-analysis of the risk of hearing loss, calculating pooled
      proportions of children with hearing loss after nonprimary and primary infection.
      Subsequently, the model was applied for worldwide present population
      seroprevalences (range 30-95%). It was estimated that, for all population
      seroprevalences, nonprimary maternal infections are responsible for the majority
      of congenital CMV infections. This proportion increased with seroprevalence,
      ranging from 57% (95%CI 24-85%) to 96% (95% CI 88-99%) for seroprevalences of 30%
      to 95%. Our meta-analysis (six reports) showed that the risk of hearing loss
      after nonprimary infection was 11% (28/253 children, 95% CI 7-15%) versus 13%
      (50/385 children, 95% CI 10-16%) after primary infection. Incorporating this risk
      into our model, we estimated that nonprimary infections also accounted for the
      majority of CMV-related hearing loss. This proportion ranged from 53% (95% CI 13
      86%) to 95% (95% CI 62-99%) for seroprevalences of 30% to 95%. Our data underline
      the worldwide contribution of nonprimary infections in causing CMV-related
      hearing loss. These results imply that prevention research such as vaccine and
      hygiene studies should not only be directed at seronegative but also seropositive
      pregnant women.

PMID- 23559570
TI  - Determination of glutathione and cysteine in yeasts by hydrophilic interaction
      liquid chromatography followed by on-line postcolumn derivatization.
AB  - In the present study, we report a new method for the determination of two primary
      thiols, cysteine (CYS) and glutathione (GSH), by hydrophilic interaction LC. The
      polar analytes are separated isocratically using a mobile phase consisting of 65%
      acetonitrile/35% ammonium acetate (15 mmol/L, pH 2.0) and are detected at 285 nm
      following on-line postcolumn derivatization by the thiol-selective reagent methyl
      propiolate. The main figures of merit included linearity in the range of 5-200
      MUmol/L and an LOD 0.6 MUmol/L for both compounds. The absence of matrix effect
      allowed the determination of CYS and GSH in various yeast samples. GSH was
      present in most of the samples at levels ranging between 0.9 and 3.1 mg/g,
      whereas CYS was determined in only one sample at a significantly lower
      concentration. In terms of accuracy, the percent recoveries ranged between 91.2
      and 105.6% for GSH, and 91.6 and 106.9% for CYS.

PMID- 23559571
TI  - New oral health literacy instrument for public health: development and pilot
      testing.
AB  - AIM: The aim of the present study was to develop a functional oral health
      literacy (OHL) instrument for adults, including new measures of literacy skills
      (OHL Adults Questionnaire: OHL-AQ). METHODS: An item pool was provided, and an
      expert panel evaluated the items by assessing the content validity index and
      content validity ratio. The reliability analysis, including internal consistency
      and reproducibility, were examined using Cronbach's alpha coefficient and
      intraclass correlation coefficient (ICC). In addition a known-groups comparison
      was performed to assess how well the questionnaire discriminates between
      individuals who differ in education and brushing behavior. RESULTS: A total of 97
      participants were studied. The mean age of the participants was 36.3 (standard
      deviation [SD] = 12.8) years; 34% had more than 12 years' formal education.
      Overall, 39.2% of interviewees had inadequate, 16.5% had marginal, and 44.3% had
      adequate OHL. The internal consistency, as measured by Cronbach's alpha, was
      found to be 0.72, and the ICC was 0.84. Participants who brushed more frequently
      had significantly higher OHL scores (P = 0.03). The association between OHL
      scores and years of education was also significant (P < 0.001). CONCLUSION: The
      OHL-AQ is a valid and reliable measure of functional OHL, with additional
      sections for evaluating listening and decision-making skills.

PMID- 23559572
TI  - Cation exchange/hydrophobic interaction monolithic chromatography of small
      molecules and proteins by nano liquid chromatography.
AB  - In this study, vinyl phenyl boronic acid modified lauryl methacrylate-based
      monolithic column was successfully prepared for cation exchange/hydrophobic
      interaction monolithic chromatography of small molecules and proteins in nano LC.
      The polymeric mixture consisted of lauryl methacrylate, vinyl phenyl boronic acid
      as cation exchanger, ethylene dimethacrylate as cross-linker, polyethylene glycol
      and methanol as binary porogenic solvent, and azobisisobutyronitrile as
      initiator. The resulting monolith showed good permeability and mechanical
      stability. Different ratios of monomer and porogens were used for optimizing the
      properties of the column. The monolithic column performance with respect to
      hydrophobic and cation exchange interactions was assessed by the separation a
      series of alkyl benzenes and anilines, respectively. cis-Diol-containing
      compounds such as phenols were also utilized to evaluate the retention behaviors
      of the vinyl phenyl boronic acid modified monolithic column. The monolithic
      column showed cation exchange interactions in the separation of aniline
      compounds. Theoretical plate number up to 52,000 plates/m was successfully
      achieved. The prepared monolith was further applied to the proteins with
      different acetonitrile content.

PMID- 23559573
TI  - TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary
      and update.
AB  - Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP
      43, were identified in amyotrophic lateral sclerosis (ALS) patients.
      Interestingly, TDP-43 positive inclusion bodies were first discovered in
      ubiquitin-positive, tau-negative ALS and frontotemporal dementia (FTD) inclusion
      bodies, and subsequently observed in the majority of neurodegenerative disorders.
      To date, 47 missense and one truncating mutations have been described in a large
      number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS)
      was found to be responsible for a previously identified ALS6 locus, being mutated
      in both FALS and SALS patients. TARDBP and FUS have a structural and functional
      similarity and most of mutations in both genes are also clustered in the C
      terminus of the proteins. The molecular mechanisms through which mutant TDP-43
      and FUS may cause motor neuron degeneration are not well understood. Both
      proteins play an important role in mRNA transport, axonal maintenance, and motor
      neuron development. Functional characterization of these mutations in in vitro
      and in vivo systems is helping to better understand how motor neuron degeneration
      occurs. This report summarizes the biological and clinical relevance of TARDBP
      and FUS mutations in ALS. All the data reviewed here have been submitted to a
      database based on the Leiden Open (source) Variation Database (LOVD) and is
      accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS.

PMID- 23559574
TI  - Optimizing the identification of patients with axial spondyloarthritis in primary
      care--the case for a two-step strategy combining the most relevant clinical items
      with HLA B27.
AB  - OBJECTIVES: The combination of clinical items suggestive of inflammatory back
      pain has proved useful for early identification of patients with axial SpA
      (axSpA) in primary care. However, whether HLA B27 contributes to that is unclear,
      and published recommendations have advised against it. In this study, we
      reanalysed data of that trial in relation to the HLA B27 results. METHODS:
      Consecutive patients <45 years old (n = 950) with back pain (BP) >2 months
      presenting to 143 orthopaedists were referred to 36 rheumatologists who made the
      diagnosis. The predictive value of HLA B27 (n = 298) alone and in combination,
      including modelling and a two-step strategy, was calculated. RESULTS: Among all
      patients (mean age 36 years, 52% female, median duration of BP 32 months), 107
      had axSpA (36%). Using a simple model, HLA B27 alone performed better than all
      combinations of clinical items and adding it did not improve likelihood ratios
      (LRs). Using modelling, two-phase strategies were analysed. Additional items were
      only relevant in the HLA B27-negative group: improvement by movement, buttock
      pain and psoriasis. Combining this information revealed the presumably best
      strategy to predict axSpA in primary care: more than one of these items or HLA
      B27 need to be present (sensitivity 80.4%, specificity 75.4%, LR+ 3.27 and LR-
      0.26). CONCLUSION: This is the first study to show that patients with axSpA are
      more reliably identified in primary care by a strategy that includes HLA B27.
      Because of the two-step approach, the test needs to be performed in only about
      half of patients with chronic BP.

PMID- 23559575
TI  - Lack of efficacy of tocilizumab in mucocutaneous Behcet's syndrome: report of two
      cases.

PMID- 23559577
TI  - Tetrahydrobiopterin, its mode of action on phenylalanine hydroxylase, and
      importance of genotypes for pharmacological therapy of phenylketonuria.
AB  - In about 20%-30% of phenylketonuria (PKU) patients (all phenotypes of PAH
      deficiency), Phe levels may be controlled through phenylalanine hydroxylase
      cofactor tetrahydrobiopterin therapy. These patients can be diagnosed by an oral
      tetrahydrobiopterin challenge and are characterized by mutations coding for
      proteins with substantial residual PAH activity. They can be treated with a
      commercially available synthetic form of tetrahydrobiopterin, either as a
      monotherapy or as adjunct to the diet. This review article summarizes molecular
      and metabolic bases of PKU and the importance of the tetrahydrobiopterin loading
      test used for PKU patients. On the basis of in vitro residual PAH activity, more
      than 1,200 genotypes from patients challenged with tetrahydrobiopterin were
      categorized as predictive for tetrahydrobiopterin responsiveness or non
      responsiveness and correlated with the loading test, phenotype, and residual in
      vitro PAH activity. The coexpression of two distinct PAH mutant alleles revealed
      possible dominance effects (positive or negative) by one of the mutations on
      residual activity as result of interallelic complementation. The treatment of the
      transfected cells with tetrahydrobiopterin showed an increase in residual PAH
      activity with several mutations coexpressed.

PMID- 23559578
TI  - A high selective ion-imprinted polymer grafted on a novel nanoporous material for
      efficient gold extraction.
AB  - In this work, for the first time, an ion-imprinted polymer was developed for
      selective extraction and determination of gold ions. To increase the sorbent
      efficiency, this polymer was coated on a novel nanoporous carbon-based material,
      carbohydrate-derived Max-Planck Gesellschaft 1, which is also the first example
      of grafting imprinted polymer on nanoporous-carbon material. These particles were
      applied successfully for preconcentration of ultratrace amount of gold ions,
      following determination by flame atomic absorption spectrometry. Some effective
      factors on the efficiency of gold ions extraction, such as concentration and
      volume of eluent, sample and eluent flow rates, and also effect of interfering
      ions especially palladium and platinum ions, were investigated. The LOD was
      determined to be 0.27 ng/mL. Furthermore, the precision of the method was
      calculated to be 2.14% under optimal conditions with recovery more than 97.3%.
      The technique was also used to determine the concentration of gold ions in mine
      stone samples with satisfactory results. The accuracy of this method was
      investigated by determination of gold ions concentrations in several reference
      materials with certified gold content.

PMID- 23559579
TI  - Stereoselective determination of ginsenosides Rg3 and Rh2 epimers in rat plasma
      by LC-MS/MS: application to a pharmacokinetic study.
AB  - We developed and validated an accurate and sensitive LC-MS/MS method for the
      simultaneous quantitation of ginsenoside Rg3 and Rh2 epimers (R-Rg3, S-Rg3, R
      Rh2, and S-Rh2) in rat plasma. Analytes were extracted from 0.1 mL aliquots of
      rat plasma by liquid-liquid extraction, using 2 mL of ethyl acetate. In this
      assay, dioscin (500 ng/mL) was used as an internal standard. Chromatographic
      separation was conducted using an Acclaim RSLC C18 column (150 * 2.1 mm, 2.2 MUm)
      at 40 degrees C, with a gradient mobile phase consisting of 0.1% formic acid in
      distilled water and in acetonitrile, a flow rate of 0.35 mL/min, and a total run
      time of 20 min. Detection and quantification were performed using a mass
      spectrometer in selected reaction-monitoring mode with negative electrospray
      ionization at m/z 783.4 -> 161.1 for R-Rg3 and S-Rg3, m/z 621.3 -> 161.1 for R
      Rh2 and S-Rh2, and m/z 867.2 -> 761.5 for the internal standard. For R-Rg3 and S
      Rg3, the lower limit of quantification was 5 ng/mL, with a linear range up to 500
      ng/mL; for R-Rh2 and S-Rh2, the lower limit of quantification was 150 ng/mL, with
      a linear range up to 6000 ng/mL. The coefficient of variation for assay precision
      was less than 10.5%, with an accuracy of 86.4-112%. No relevant cross-talk or
      matrix effect was observed. The method was successfully applied to a
      pharmacokinetic study after oral administration of 400 mg/kg and 2000 mg/kg of
      BST204, a fermented ginseng extract, to rats. We found that the S epimers
      exhibited significantly higher plasma concentrations and area under curve values
      for both Rg3 and Rh2. This is the first report on the separation and simultaneous
      quantification of R-Rg3, S-Rg3, R-Rh2, and S-Rh2 in rat plasma by LC-MS/MS. The
      method should be useful in the clinical use of ginseng or its derivatives.

PMID- 23559580
TI  - AKI in an HIV patient.
AB  - The renal manifestations of patients infected with HIV are diverse. Patients may
      have podocytopathies ranging from a minimal-change-type lesions to FSGS or
      collapsing glomerulopathy. Furthermore, such patients produce a variety of
      autoantibodies without clinical signs of the disease. Antiretroviral drugs also
      cause renal injury, including crystals and tubular injury, acute interstitial
      nephritis, or mitochondrial toxicity. In these circumstances, it is essential to
      perform a renal biopsy for diagnosis and to guide treatment. Here we describe a
      patient with HIV who presented with AKI and hematuria without concomitant
      systemic manifestations. Renal biopsy elucidated the cause of acute deterioration
      of kidney function. 

PMID- 23559581
TI  - Association between younger age when first overweight and increased risk for CKD.
AB  - There is little information on how the duration of overweight or obesity during
      life affects the risk for CKD. To investigate whether prolonged exposure to
      overweight during adult life increases the risk of later CKD in a cumulative
      manner, we analyzed data from the Medical Research Council National Survey of
      Health and Development, a socially stratified sample of 5362 singleton children
      born in 1 week in March 1946 in England, Scotland, and Wales. Multiple imputation
      expanded the analysis sample from the initial 1794 participants with complete
      data to 4584. This study collected self-reported body mass index (BMI) at ages 20
      and 26 years and measured BMI at ages 36, 43, 53, and 60-64 years. The outcome of
      interest was CKD at age 60-64 years, suggested by estimated GFR (eGFR) <60 ml/min
      per 1.73 m(2) and/or urine albumin-to-creatinine ratio (UACR) >= 3.5 mg/mmol. In
      analyses adjusted for childhood and adulthood social class, first becoming
      overweight at younger ages was associated with higher odds of developing CKD by
      age 60-64 years. Compared with those who first became overweight at age 60-64
      years or never became overweight, those first overweight at age 26 or 36 years
      had approximately double the odds of developing CKD. The strength of this
      association decreased with increasing age when first overweight (P for trend
      <0.001). These associations were consistent for creatinine-based eGFR, cystatin C
      based eGFR, and UACR. Taken together, these results suggest that preventing
      overweight in early adulthood may have a considerable effect on the prevalence of
      CKD in the population.

PMID- 23559582
TI  - Renoprotective effect of combined inhibition of angiotensin-converting enzyme and
      histone deacetylase.
AB  - The Connectivity Map database contains microarray signatures of gene expression
      derived from approximately 6000 experiments that examined the effects of
      approximately 1300 single drugs on several human cancer cell lines. We used these
      data to prioritize pairs of drugs expected to reverse the changes in gene
      expression observed in the kidneys of a mouse model of HIV-associated nephropathy
      (Tg26 mice). We predicted that the combination of an angiotensin-converting
      enzyme (ACE) inhibitor and a histone deacetylase inhibitor would maximally
      reverse the disease-associated expression of genes in the kidneys of these mice.
      Testing the combination of these inhibitors in Tg26 mice revealed an additive
      renoprotective effect, as suggested by reduction of proteinuria, improvement of
      renal function, and attenuation of kidney injury. Furthermore, we observed the
      predicted treatment-associated changes in the expression of selected genes and
      pathway components. In summary, these data suggest that the combination of an ACE
      inhibitor and a histone deacetylase inhibitor could have therapeutic potential
      for various kidney diseases. In addition, this study provides proof-of-concept
      that drug-induced expression signatures have potential use in predicting the
      effects of combination drug therapy.

PMID- 23559583
TI  - Small-molecule screening identifies modulators of aquaporin-2 trafficking.
AB  - In the principal cells of the renal collecting duct, arginine vasopressin (AVP)
      stimulates the synthesis of cAMP, leading to signaling events that culminate in
      the phosphorylation of aquaporin-2 water channels and their redistribution from
      intracellular domains to the plasma membrane via vesicular trafficking. The
      molecular mechanisms that control aquaporin-2 trafficking and the consequent
      water reabsorption, however, are not completely understood. Here, we used a cell
      based assay and automated immunofluorescence microscopy to screen 17,700 small
      molecules for inhibitors of the cAMP-dependent redistribution of aquaporin-2.
      This approach identified 17 inhibitors, including 4-acetyldiphyllin, a selective
      blocker of vacuolar H(+)-ATPase that increases the pH of intracellular vesicles
      and causes accumulation of aquaporin-2 in the Golgi compartment. Although 4
      acetyldiphyllin did not inhibit forskolin-induced increases in cAMP formation and
      downstream activation of protein kinase A (PKA), it did prevent cAMP/PKA
      dependent phosphorylation at serine 256 of aquaporin-2, which triggers the
      redistribution to the plasma membrane. It did not, however, prevent cAMP-induced
      changes to the phosphorylation status at serines 261 or 269. Last, we identified
      the fungicide fluconazole as an inhibitor of cAMP-mediated redistribution of
      aquaporin-2, but its target in this pathway remains unknown. In conclusion, our
      screening approach provides a method to begin dissecting molecular mechanisms
      underlying AVP-mediated water reabsorption, evidenced by our identification of 4
      acetyldiphyllin as a modulator of aquaporin-2 trafficking.

PMID- 23559585
TI  - An update on mobile phones interference with medical devices.
AB  - Mobile phones' electromagnetic interference with medical devices is an important
      issue for the medical safety of patients who are using life-supporting medical
      devices. This review mainly focuses on mobile phones' interference with implanted
      medical devices and with medical equipment located in critical areas of
      hospitals. A close look at the findings reveals that mobile phones may adversely
      affect the functioning of medical devices, and the specific effect and the degree
      of interference depend on the applied technology and the separation distance.
      According to the studies' findings and the authors' recommendations, besides
      mitigating interference, using mobile phones at a reasonable distance from
      medical devices and developing technology standards can lead to their effective
      use in hospital communication systems. 

PMID- 23559584
TI  - Loss of Klotho contributes to kidney injury by derepression of Wnt/beta-catenin
      signaling.
AB  - Aging is an independent risk factor for CKD, but the molecular mechanisms that
      link aging and CKD are not well understood. The antiaging protein Klotho may be
      an endogenous antagonist of Wnt/beta-catenin signaling, which promotes
      fibrogenesis, suggesting that loss of Klotho may contribute to CKD through
      increased Wnt/beta-catenin activity. Here, normal adult kidneys highly expressed
      Klotho in the tubular epithelium, but various models of nephropathy exhibited
      markedly less expression of Klotho. Loss of Klotho was closely associated with
      increased beta-catenin in the diseased kidneys, suggesting an inverse correlation
      between Klotho and canonical Wnt signaling. In vitro, both full-length and
      secreted Klotho bound to multiple Wnts, including Wnt1, Wnt4, and Wnt7a. Klotho
      repressed gene transcription induced by Wnt but not by active beta-catenin.
      Furthermore, Klotho blocked Wnt-triggered activation and nuclear translocation of
      beta-catenin, as well as the expression of its target genes in tubular epithelial
      cells. Investigating potential mediators of Klotho loss in CKD, we found that TGF
      beta1 suppressed Klotho expression and concomitantly activated beta-catenin;
      conversely, overexpression of Klotho abolished fibrogenic effects of TGF-beta1.
      In two mouse models of CKD induced by unilateral ureteral obstruction or
      adriamycin, in vivo expression of secreted Klotho inhibited the activation of
      renal beta-catenin and expression of its target genes. Secreted Klotho also
      suppressed myofibroblast activation, reduced matrix expression, and ameliorated
      renal fibrosis. Taken together, these results suggest that Klotho is an
      antagonist of endogenous Wnt/beta-catenin activity; therefore, loss of Klotho may
      contribute to kidney injury by releasing the repression of pathogenic Wnt/beta
      catenin signaling.

PMID- 23559586
TI  - 210Po and 238U isotope concentrations in commercial bottled mineral water samples
      in Spain and their dose contribution.
AB  - (210)Po is a naturally occurring radionuclide, belonging to the uranium series,
      which is present in minute amounts in the different environmental compartments
      (water, soil, biota). Through its route along the trophic chain, it can be
      incorporated in the human body via ingestion of waters and/or food. This
      radionuclide is highly radiotoxic, being one of the main contributors to the
      committed effective dose via ingestion by the general population. In this work,
      the contribution of this radionuclide to the committed effective dose received by
      the Spanish population via consumption of bottled mineral waters is evaluated.
      With this end, the (210)Po activity concentrations in a total of 32 different
      commercial bottled mineral waters have been determined by alpha-particle
      spectrometry. The determined contribution is also compared with the contributions
      of other natural radionuclides such as (234)U and (238)U. 

PMID- 23559587
TI  - Enriching the interventional vision of cancer with fluorescence and optoacoustic
      imaging.
AB  - Among several techniques considered for surgical and endoscopic imaging, novel
      optical methods are evolving as a promising approach for interventional guidance.
      Pilot clinical applications of fluorescence molecular imaging have demonstrated
      the benefits of using targeted fluorescent agents in cancer surgery. This premise
      can be extended broadly to interventional guidance through an increasing number
      of targeted agents and detection techniques. Beyond epi-illumination fluorescence
      imaging, optoacoustic (photoacoustic) methods are emerging to offer high
      resolution cross-sectional optical imaging through several millimeters to
      centimeters of depth. We present an overview of key recent developments in
      optical interventional imaging and outline the potential for a paradigm shift in
      surgical and endoscopic visualization.

PMID- 23559588
TI  - Impact of 18F-choline PET/CT in prostate cancer patients with biochemical
      recurrence: influence of androgen deprivation therapy and correlation with PSA
      kinetics.
AB  - We evaluated the potential of (18)F-fluoromethyldimethyl-2-hydroxyethyl-ammonium
      (FCH) PET/CT in the detection of recurrent disease or distant metastases and
      correlated its diagnostic accuracy with prostate-specific antigen (PSA) levels in
      prostate cancer patients with biochemical evidence of recurrence. Furthermore,
      the influences of androgen deprivation therapy (ADT) and its duration on (18)F
      FCH PET were assessed in this study. METHODS: This prospective study included 250
      prostate cancer patients with PSA relapse who underwent (18)F-FCH PET/CT. At the
      time of (18)F-FCH PET/CT imaging, the mean PSA level was 46.9 +/- 314.7 ng/mL and
      55.2% (138/250) of patients were receiving ADT. Overall, ADT was performed on
      67.2% (168/250) of patients after initial treatment. Imaging was performed on an
      integrated PET/CT system. Acquisition started 1 min after intravenous injection
      of (18)F-FCH (4.07 MBq/kg of body weight) with dynamic PET images in the pelvic
      region during 8 min (1 min/frame) followed by a static semi-whole-body
      acquisition. The final diagnosis of positive PET lesions was based on
      histopathology or a consensus of clinical findings, additional imaging, or follow
      up imaging modalities. RESULTS: (18)F-FCH PET/CT was able to correctly detect
      malignant lesions in 74% (185/250) of patients but was negative in 26% (65/250).
      In 28% of patients, only 1 lesion was detected (69/250); from these, 65.2% (45
      patients) had a local recurrence, 18.8% (13 patients) a single lymph node, and
      15.9% (11 patients) a solitary bone metastasis. The sensitivity of the (18)F-FCH
      PET was significantly higher (P = 0.001) in patients with ongoing ADT (85%;
      confidence interval, 80%-91%) than in patients without ADT (59.5%; confidence
      interval, 50%-69%). (18)F-FCH PET sensitivity was 77.5%, 80.7%, 85.2%, and 92.8%
      for the trigger PSA levels of more than 0.5, 1.0, 2.0, and 4.0 ng/mL,
      respectively. Scan sensitivity was 33% in patients with a trigger PSA level of
      less than 0.3 ng/mL and 77% in patients with a trigger PSA level of greater than
      0.3 ng/mL, respectively (P = 0.001). Using a binary logistic regression analysis
      model, we showed trigger PSA and ADT to be the only significant predictors of
      positive PET findings. CONCLUSION: (18)F-FCH PET/CT proved its potential as a
      noninvasive 1-stop diagnostic modality enabling us to correctly detect occult
      disease in 74% of patients and to differentiate localized from systemic disease.
      In patients with biochemical recurrence, it also guides to an optimal treatment
      approach after initial treatment. Trigger PSA and ADT are the 2 significant
      predictors of (18)F-FCH-positive PET lesions. ADT seems not to impair (18)F-FCH
      uptake in hormone-refractory prostate cancer patients.

PMID- 23559590
TI  - European guidelines for sclerotherapy in chronic venous disorders.
AB  - AIM: Sclerotherapy is the targeted chemical ablation of varicose veins by
      intravenous injection of a liquid or foamed sclerosing drug. The treated veins
      may be intradermal, subcutaneous, and/or transfascial as well as superficial and
      deep in venous malformations. The aim of this guideline is to give evidence-based
      recommendations for liquid and foam sclerotherapy. METHODS: This guideline was
      drafted on behalf of 23 European Phlebological Societies during a Guideline
      Conference on 7-10 May 2012 in Mainz. The conference was organized by the German
      Society of Phlebology. These guidelines review the present state of knowledge as
      reflected in published medical literature. The regulatory situation of sclerosant
      drugs differs from country to country but this has not been considered in this
      document. The recommendations of this guideline are graded according to the
      American College of Chest Physicians Task Force recommendations on Grading
      Strength of Recommendations and Quality of Evidence in Clinical Guidelines.
      RESULTS: This guideline focuses on the two sclerosing drugs which are licensed in
      the majority of the European countries, polidocanol and sodium tetradecyl
      sulphate. Other sclerosants are not discussed in detail. The guideline gives
      recommendations concerning indications, contraindications, side-effects,
      concentrations, volumes, technique and efficacy of liquid and foam sclerotherapy
      of varicose veins and venous malformations.

PMID- 23559591
TI  - Inequalities of health insurance guidelines for the treatment of symptomatic
      varicose veins.
AB  - OBJECTIVES: The emerging model of US health-care delivery is aimed at reducing
      costs, standardizing care, and improving outcomes. Although it is necessary for
      health-care providers and insurance carriers to work together to achieve those
      goals, insurers have the added duty of assuring physicians and patients that they
      comprehend the medical evidence and, based on that understanding, construct
      policies. Are US insurers meeting that responsibility or are they simply creating
      policies to serve their own needs? METHODS: The medical policies of several US
      health insurers were analysed. The goal was to see whether it could readily be
      determined if these carriers used evidence-based medicine consistently to create
      uniform policies for the treatment of patients with symptomatic varicose veins.
      The literature was also reviewed to determine whether increased insurance
      documentation requirements have affected cost reduction, standardization of care
      and/or improvement of outcomes related to chronic vein disease management.
      RESULTS: There is a dramatic lack of uniformity among the insurance policies
      reviewed. Insurers appear to not choose important papers to create policy but use
      carefully chosen articles to reinforce what they want their policies to say. In
      so doing, conflicting policy criteria are being created. Complicating this
      inconsistency, rules for medical necessity are modified frequently, raising
      frustration levels among vein providers and their patients. What is clear is that
      costs are not being lowered, care is not being standardized and little is being
      done to prevent potential complications resulting from chronic vein disease.
      CONCLUSIONS: Patients and physicians are increasingly ill-served by, and
      frustrated with, the clear lack of consistency in the medical policy criteria
      being created by US insurance carriers in covering the treatment of patients with
      symptomatic varicose veins. The contradictory coverage requirements, seemingly
      based on no understanding of evidence-based medicine guidelines, and total
      variability in reimbursement for various types of treatment options is
      particularly worrisome. Collaboration between venous treatment providers and
      insurance carriers, to create evidence-based standards of care, would be timely
      and beneficial in creating guidelines for optimal patient care.

PMID- 23559592
TI  - Translation and validation of the Dutch VEINES-QOL/Sym in varicose vein patients.
AB  - OBJECTIVES: To translate from English to Dutch and evaluate the psychometric
      properties of the VEnous INsufficiency Epidemiological and Economic Studies
      (VEINES) questionnaire, divided in symptom (VEINES-Sym) and quality of life
      (VEINES-QOL) subscales. METHODS: Standard forward-backward translation method was
      used to translate the 26 items of the VEINES-QOL/Sym. Eligible patients had to
      complete a standardized questionnaire. Demographic, venous disease
      characteristics, clinical venous signs, CEAP (clinical, aetiological, anatomical
      and pathological elements) classification and ultrasound findings were also
      noted. If item's scores were in an extreme category in more than 70% of patients
      a floor or ceiling effect was present. Feasibility of the individual items was
      considered poor if 5% or more of the responses were missing. The validity was
      tested by comparing the VEINES-QOL/Sym scores to the Short Form 36 (SF-36) scores
      and across the different 'CEAP' categories. Confirmatory factor analysis was used
      to assess the underlying structure of the VEINES-QOL/Sym. RESULTS: Sixty-six
      patients were included (response rate of 72%). None of the 26 items missed <10%
      of responses, but two showed ceiling effect. Both the VEINES-QOL and VEINES-Sym
      showed an excellent internal consistency (Cronbach's alpha of 0.88 and 0.81,
      respectively). The VEINES-QOL demonstrated a good construct validity for the
      physical component of the SF-36, but not for the mental component (rho = 0.62 and
      0.22, respectively), as expected. The VEINES-Sym correlated poorly to both SF
      36's components. According to the confirmatory principle axis factoring, only
      three out of 25 items did not load sufficiently on the factor. CONCLUSIONS: The
      Dutch VEINES-QOL/Sym can be used for health-related quality of life research in
      varicose veins patients and the evaluation of therapies.

PMID- 23559594
TI  - No second-order motion system sensitive to high temporal frequencies.
AB  - It has been shown that the perception of contrast-defined motion (i.e., a second
      order stimulus) at high temporal frequencies cannot be explained solely by global
      distortion products (i.e., luminance artifacts due to preprocessing
      nonlinearities) processed by the first-order system. However, previous studies
      rejecting the first-order pathway hypothesis have assumed that the preprocessing
      nonlinearities are identical for all first-order motion units. If this is not the
      case, then introducing a nonlinearity within the stimulus could neutralize the
      global (i.e., mean) distortion product but would leave residual distortion
      products. We neutralized either global only or both global and residual
      distortion products by superimposing a luminance modulation onto the contrast
      modulation. At a temporal frequency too high for features to be tracked (15 Hz),
      we found a substantial texture (i.e., contrast-modulated) contribution to motion
      when neutralizing only global distortion products but not when neutralizing both
      global and residual distortion products. Furthermore, we found that the texture
      contribution to motion at this high temporal frequency, when it was not
      completely neutralized, depended on the phase difference between luminance and
      contrast modulations, which implied some common processing before the motion
      extraction stage. We concluded that the texture contribution to motion at high
      temporal frequencies was due to nonuniform preprocessing nonlinearities within
      the visual system, enabling first-order motion units to process distortion
      products, and not due to a dedicated second-order motion system.

PMID- 23559593
TI  - How your hand drives my eyes.
AB  - When viewing object-related hand actions people make proactive eye movements of
      the same kind as those made when performing such actions. Why is this so? It has
      been suggested that proactive gaze when viewing a given hand action depends on
      the recruitment of motor areas such as the ventral premotor (PMv) cortex that
      would be involved in the execution of that action. However, direct evidence for a
      distinctive role of the PMv cortex in driving gaze behavior is still lacking. We
      recorded eye moments while viewing hand actions before and immediately after
      delivering repetitive transcranial magnetic stimulation (rTMS) over the left PMv
      and the posterior part of the left superior temporal sulcus, which is known to be
      involved in high-order visual action processing. Our results showed that rTMS
      induced effects were selective with respect to the viewed actions following the
      virtual lesion of the left PMv only. This, for the first time, provides direct
      evidence that the PMv cortex might selectively contribute to driving the viewer's
      gaze to the action's target. When people view another's action, their eyes may be
      driven by motor processes similar to those they would need to perform the action
      themselves. 

PMID- 23559595
TI  - Spatial organization affects lightness perception on articulated surrounds.
AB  - The articulation effect refers to a change in lightness contrast induced by
      adding small patches of different luminances to a uniform background surrounding
      a target in a lightness contrast display. This study investigated how local
      luminance signals are integrated to generate the articulation effect. We asked
      whether spatial organization due to perceptual grouping can influence the
      articulation effect even when the spatially averaged luminance of the surrounds
      is held constant. Grouping factors used were common-fate motion (Experiment 1),
      similarity of orientation (Experiment 2), and synchrony (Experiment 3). Results
      of all experiments consistently showed that the articulation effect was larger
      when the target was strongly grouped with the articulation patches. These
      findings provide converging evidence for the effects of spatial organization on
      the articulation effect. Moreover, they suggest that lightness computation
      underlying the articulation effect depends on a middle-level representation in
      which perceptual organization is at least partially established. The changes in
      lightness perception due to spatial organization could be accounted for by the
      double-anchoring theory of lightness (Bressan, 2006b).

PMID- 23559596
TI  - Prevalence of latent tuberculosis, syphilis, hepatitis B and C among asylum
      seekers in Malta.
AB  - BACKGROUND: In the last few years, Malta has witnessed increasing immigration
      flows from the Libyan coasts. Public health policies are focused on screening
      migrants for tuberculosis, whereas no systematic actions against STIs are
      implemented. The aim of this study is to define the epidemiological profile of
      asylum seekers in Malta as regards syphilis, hepatitis B, C and latent
      tuberculosis, thus supporting screening policies. METHODS: Five hundred migrants
      living in open centres were screened between December 2010 and June 2011.
      RESULTS: 83.2% of people was from Somalia, 81.2% males, average age 26.5 years.
      The tuberculin skin test (TST) was positive in 225 migrants (45%). Latent
      syphilis was diagnosed in 11 migrants, hepatitis C in 3 and 31 migrants were
      HBsAg positive. CONCLUSION: Systematic screening for asymptomatic migrants in
      Malta is not recommended for hepatitis C and syphilis, given the low prevalence
      observed. On the contrary, it should be considered for hepatitis B. TST could be
      indicated as the first step of a two step screening for migrants from countries
      with high TB incidence. Efficacy and cost-effectiveness could be achieved by
      further targeting screening to specific subgroups at higher risk of reactivation,
      such as people living with HIV and subjects affected by chronic diseases.

PMID- 23559597
TI  - Follow-up study of abnormal biological indicators and gene expression in the
      peripheral blood of three accidentally exposed persons.
AB  - In order to identify biomarkers for early diagnosis and/or for therapeutic
      targets in the delayed health effects of ionizing radiation, we analyzed the
      subgroups of lymphocytes, serum protein levels and gene expression profiles in
      the peripheral blood of three 60Co gamma-ray accidentally exposed persons during
      the three years after irradiation. Flow cytometry analyses and agarose gel
      electrophoresis were applied to investigate the subgroups of lymphocytes and the
      composition of serum proteins, respectively. Gene expression profiling was
      obtained using a whole genome gene expression chip assay. Both the percentage of
      CD4+ T lymphocytes and the ratio of Th to Ts were reduced compared with the
      normal control values. The percentage of albumin decreased whereas beta globulin
      increased. There were 285 up-regulated and 446 down-regulated genes in irradiated
      samples relative to the control samples. The expression of KDR, CEACAM8 and OSM
      was validated by RT-PCR. The majority of the differentially expressed genes
      encode proteins associated with the immune response, inflammation, oncogenesis,
      cell structure, oxidative stress, neuro-hormone regulation, reproduction,
      susceptibility to psychiatric disorders, or transcriptional regulation. We have
      identified a number of promising novel candidates that have potential for serving
      as biomarkers for delayed damage. Furthermore, the changes in the immunological
      indicator CD4+ T cells, and the ratio of CD4+ T to CD8+ T cells may be biomarkers
      for the prediction of delayed damage by ionizing radiation. The findings of our
      study are useful for forming a comprehensive understanding of the mechanisms
      underlying the delayed effects of ionizing radiation.

PMID- 23559598
TI  - Postoperative radiotherapy in patients with salivary duct carcinoma: clinical
      outcomes and prognostic factors.
AB  - This study sought to investigate the clinical outcome and the role of
      postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who
      had undergone surgery and postoperative radiotherapy. We performed a
      retrospective analysis of 25 SDC patients treated between 1998 and 2011 with
      surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy
      (range, 49.5-61.4 Gy). The clinical target volume (CTV) was defined as the tumor
      bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the
      tumor bed and bilateral neck in six patients. Local control (LC), disease-free
      survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier
      method, and prognostic variables were analyzed with the log-rank test. The 5-year
      LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found
      in 12 patients: seven as local, four as regional and eight as distant failure.
      Perineural and lymphovascular invasion was a significant prognostic factor for LC
      (P = 0.03). Local failure was common, and the presence of local recurrence
      significantly affected the OS (P < 0.05). We conclude that surgery and
      postoperative radiotherapy is expected to decrease the risk of local failure and
      contribute to good prognoses for patients with SDC. It might be advisable to have
      the CTV include the cranial nerves involved and the corresponding parts of the
      skull base in cases of pathologically positive perineural invasion. 

PMID- 23559599
TI  - Radiation therapy for primary vaginal carcinoma.
AB  - Brachytherapy plays a significant role in the management of cervical cancer, but
      the clinical significance of brachytherapy in the management of vaginal cancer
      remains to be defined. Thus, a single institutional experience in the treatment
      of primary invasive vaginal carcinoma was reviewed to define the role of
      brachytherapy. We retrospectively reviewed the charts of 36 patients with primary
      vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The
      treatment modalities included high-dose-rate intracavitary brachytherapy alone
      (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14
      patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate
      interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2
      months. The 2-year local control rate (LCR), disease-free survival (DFS), and
      overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR
      for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P =
      0.007). In subgroup analysis consisting only of T2-T3 disease, the use of HDR
      ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P =
      0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a
      vaginal ulcer. We conclude that brachytherapy can play a central role in
      radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2
      T3 disease resulted in good local control. 

PMID- 23559600
TI  - Children travelling for treatment: what we don't know.
AB  - Travel for the purposes of obtaining medical treatment is increasing, but very
      little is known about the extent or nature of child medical travel. This paper
      discusses the outcome of a systematic search for academic literature on
      paediatric medical travel, outlines the potential significance of 'return health
      migration' by parents and children from minority ethnic groups in the UK, and
      suggests an agenda for future multidisciplinary research in this field.

PMID- 23559601
TI  - Apparent life-threatening events: difficult for parents, difficult for
      clinicians.

PMID- 23559602
TI  - Giant Hogweed burns.

PMID- 23559603
TI  - Protecting children and young people.

PMID- 23559604
TI  - Identification of a chloroplast ribonucleoprotein complex containing trans
      splicing factors, intron RNA, and novel components.
AB  - Maturation of chloroplast psaA pre-mRNA from the green alga Chlamydomonas
      reinhardtii requires the trans-splicing of two split group II introns. Several
      nuclear-encoded trans-splicing factors are required for the correct processing of
      psaA mRNA. Among these is the recently identified Raa4 protein, which is involved
      in splicing of the tripartite intron 1 of the psaA precursor mRNA. Part of this
      tripartite group II intron is the chloroplast encoded tscA RNA, which is
      specifically bound by Raa4. Using Raa4 as bait in a combined tandem affinity
      purification and mass spectrometry approach, we identified core components of a
      multisubunit ribonucleoprotein complex, including three previously identified
      trans-splicing factors (Raa1, Raa3, and Rat2). We further detected tscA RNA in
      the purified protein complex, which seems to be specific for splicing of the
      tripartite group II intron. A yeast-two hybrid screen and co-immunoprecipitation
      identified chloroplast-localized Raa4-binding protein 1 (Rab1), which
      specifically binds tscA RNA from the tripartite psaA group II intron. The yeast
      two hybrid system provides evidence in support of direct interactions between
      Rab1 and four trans-splicing factors. Our findings contribute to our knowledge of
      chloroplast multisubunit ribonucleoprotein complexes and are discussed in support
      of the generally accepted view that group II introns are the ancestors of the
      eukaryotic spliceosomal introns. 

PMID- 23559612
TI  - Unilateral hallux valgus: is it true unilaterality, or does it progress to
      bilateral deformity?
AB  - BACKGROUND: This study was undertaken to determine whether unilateral hallux
      valgus progresses unilaterally and to evaluate the demographics, etiologies, and
      radiographic findings associated with symptomatic unilateral hallux valgus
      deformities. METHODS: Patients treated for hallux valgus between January 2004 and
      December 2008 were identified, and of these, 33 patients with unilateral
      deformities were enrolled. Progression of deformities in normal feet were
      evaluated at last follow-up visit, and the clinical information and radiographic
      measurements of those with a deformed normal foot or an unchanged normal foot
      were compared. RESULTS: Thirty-three patients (3.4%) had a unilateral hallux
      valgus deformity on preoperative radiographs. The mean length of follow up was
      4.7 years (range, 2.4-11). Twenty-four cases had no deformity of the normal foot
      at last follow-up (the unchanged group), but 15 cases had developed hallux valgus
      deformity (the deformed group). No significant intergroup differences were found
      in terms of metatarsus adductus angle (P = .412), Meary angle (P = .771),
      talocalcaneal angle (P = 1.000), or calcaneal pitch angle (P = .267). However,
      members of the deformed group were significantly younger at disease onset (P =
      .045), exhibited a curved first metatarsal head (P = .046), and had a larger
      initial hallux valgus angle (P < .001). CONCLUSIONS: The frequency of bilateral
      symptomatic hallux valgus was found to be over 97.3%, and significant differences
      were found between the deformed and unchanged groups in terms of age of onset,
      metatarsal head shape, and hallux valgus angle.

PMID- 23559613
TI  - Costs and benefits of routine histopathological examination of hammertoe
      specimens.
AB  - BACKGROUND: The purpose of this study was to evaluate the cost and benefit of
      routinely submitting hammertoe specimens for histopathological examination. We
      hypothesized that such examination rarely shows a new diagnosis and seldom alters
      postoperative care. MATERIALS AND METHODS: Three hundred and fourteen proximal
      interphalangeal (PIP) joint and 37 extensor tendon specimens from 187 consecutive
      hammertoe correction surgeries were submitted by 2 surgeons for histopathological
      examination between January 2009 and December 2011. Each patient's chart was
      reviewed to determine whether the histopathological examination revealed a
      diagnosis other than degenerative joint or degenerative tendon and whether
      subsequent patient management was altered. The total reimbursements for
      professional charges were calculated using the average reimbursement from common
      insurance providers for two Current Procedural Terminology (CPT) codes: 88304
      (soft tissue examination) and 88311 (decalcification). RESULTS: Almost all of the
      specimens were diagnosed as degenerative: 97.5% (307/314) of the PIP specimens
      and all (37/37) of the tendon specimens. Seven PIP specimens (2.2%, 7/314) from 5
      patients (2.7%, 5/187) and no tendon specimens had other diagnoses. These
      diagnoses were rheumatoid arthritis (5/314, 1.6%), osteomyelitis (1/314, 0.3%),
      and pigmented villonodular synovitis (PVNS) (1/314, 0.3%). Only the PVNS was a
      new diagnosis. A total of $56,750 was spent to determine 1 new diagnosis.
      CONCLUSION: The routine submission of hammertoe specimens for pathological
      evaluation was not cost-efficient. Our analysis showed that new diagnoses were
      rarely found and patient management was not affected.

PMID- 23559611
TI  - Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins
      modulate sinoatrial node pacemaker function.
AB  - AIMS: Pulmonary vein ganglia (PVG) are targets for atrial fibrillation ablation.
      However, the functional relevance of PVG to the normal heart rhythm remains
      unclear. Our aim was to investigate whether PVG can modulate sinoatrial node
      (SAN) function. METHODS AND RESULTS: Forty-nine C57BL and seven Connexin40+/EGFP
      mice were studied. We used tyrosine-hydroxylase (TH) and choline
      acetyltransferase immunofluorescence labelling to characterize adrenergic and
      cholinergic neural elements. PVG projected postganglionic nerves to the SAN,
      which entered the SAN as an extensive, mesh-like neural network. PVG neurones
      were adrenergic, cholinergic, and biphenotypic. Histochemical characterization of
      two human embryonic hearts showed similarities between mouse and human
      neuroanatomy: direct neural communications between PVG and SAN. In Langendorff
      perfused mouse hearts, PVG were stimulated using 200-2000 ms trains of pulses
      (300 MUs, 400 uA, 200 Hz). PVG stimulation caused an initial heart rate (HR)
      slowing (36 +/- 9%) followed by acceleration. PVG stimulation in the presence of
      propranolol caused HR slowing (43 +/- 13%) that was sustained over 20 beats. PVG
      stimulation with atropine progressively increased HR. Time-course effects were
      enhanced with 1000 and 2000 ms trains (P < 0.05 vs. 200 ms). In optical mapping,
      PVG stimulation shifted the origin of SAN discharges. In five paroxysmal AF
      patients undergoing pulmonary vein ablation, application of radiofrequency energy
      to the PVG area during sinus rhythm produced a decrease in HR similar to that
      observed in isolated mouse hearts. CONCLUSION: PVG have functional and anatomical
      biphenotypic characteristics. They can have significant effects on the
      electrophysiological control of the SAN.

PMID- 23559614
TI  - Correction of intermetatarsal angle in hallux valgus using small suture button
      device.
AB  - BACKGROUND: Hallux valgus is a common foot ailment causing pain and disability,
      and correction of the intermetatarsal angle (IMA) deformity is often accomplished
      using a first metatarsal distal or proximal osteotomy. These osteotomies can be
      technically challenging and may lead to complications such as loss of fixation,
      shortening of the first metatarsal, avascular necrosis, malunion, and nonunion.
      Endobuttons (Mini TightRope device) provide an alternative to first metatarsal
      osteotomies for correction of the IMA. The purpose of this preliminary study was
      to determine the short-term clinical and radiographic outcomes of hallux valgus
      correction using the Mini TightRope. METHODS: A total of 14 cases of hallux
      valgus correction using the Mini TightRope technique with a 1.1-mm drill and mini
      buttress plate were reviewed. Clinical examinations and radiographs were
      performed preoperatively and postoperatively at 1-week (non-weight-bearing), 3
      month (weight-bearing), and 6-month (weight-bearing) follow-up. RESULTS: The
      overall 1-week postoperative decreases in IMA and hallux valgus angle (HVA) of
      all cases compared with preoperative status were 9 degrees and 28 degrees,
      respectively. Decreases in IMA and HVA continued at 3 months postoperatively but
      to a lesser extent, with decreases of 7 degrees and 20 degrees, respectively.
      Reductions in IMA and HVA were maintained through 6 months of follow-up compared
      with preoperatively, with IMA and HVA decreases of 6 degrees and 19 degrees,
      respectively. Two minor soft-tissue complications and 1 intraoperative second
      metatarsal fracture were treated with a buttress plate, with uneventful healing.
      CONCLUSIONS: Overall short-term results demonstrated notable improvements in IMA
      and HVA with use of the Mini TightRope, and few early complications were
      associated with the procedure.

PMID- 23559615
TI  - Computed tomography analysis of third webspace injections for interdigital
      neuroma.
AB  - BACKGROUND: Injection for interdigital neuroma (IDN) may not selectively target
      the common digital nerve. We investigated the anatomical localization and extent
      of extravasation with injection for IDN. METHODS: Two fellowship-trained foot and
      ankle surgeons injected radiopaque contrast into the third webspace of 49
      cadaveric specimens (29 with 2 mL and 20 with 1 mL). Computed tomography scan of
      each specimen was obtained. An independent blinded foot and ankle surgeon
      analyzed the scans. RESULTS: All injections were accurate. Contrast was found in
      the second (greater than 70%) and fourth (greater than 30%) webspaces in both
      injection volume groups. No contrast was found within the third
      metatarsophalangeal joint. Extravasation extent was significantly greater with 2
      mL versus 1 mL of solution in the medial to lateral (27.9 [7.8] mm vs 23.7 [6.0]
      mm; P = .05) and distal to proximal (52.1 [13.7] mm vs 40.4 [16.1] mm; P = .01)
      planes. No differences were observed in extravasation extent between surgeons.
      CONCLUSION: Injection for IDN was accurate, and extravasation extended into
      adjacent webspaces in a large percentage of specimens with both solution volumes.
      Lower extent of extravasation with 1 mL of solution did not indicate better
      selectivity of injection. CLINICAL RELEVANCE: Steroid injections for interdigital
      neuroma were accurate for therapeutic purposes but not diagnostic, except
      potentially for distinguishing webspace pain from joint pain.

PMID- 23559616
TI  - Footprint of the lateral ligament complex of the ankle.
AB  - BACKGROUND: We describe the topographic anatomy of the lateral ligament complex
      of the ankle using 3-dimensional (3D) computed tomography (CT) imaging. METHODS:
      Dissection of the anterior talofibular ligament (ATFL) and the calcaneofibular
      ligament (CFL) was performed on 8 unpaired fresh-frozen cadaver feet. Ligaments
      were sharply dissected from bone, and the footprint was outlined with radio
      opaque paint. The specimen underwent a 0.625-mm slice CT scan of the ankle with
      3D reconstructions. Software was used to determine the surface area of the
      ligament footprint as well as measure the distance from the peroneal tubercle to
      the center of the CFL footprint. Data are presented as mean +/- standard error.
      RESULTS: Six specimens had a bifid ATFL. Seven ankles had a bifid ATFL footprint
      on the talus. All specimens had intact CFL fibers. The intact superior and
      inferior limbs of the ATFL measured 19.7 +/- 1.2 mm and 16.7 +/- 1.1 mm. The CFL
      measured 24.8 +/- 2.4 mm. The area of the footprints of the superior ATFL and
      inferior ATFL on the talus measured 1.5 +/- 0.26 cm(2) and 0.90 +/- 0.07 cm(2).
      The CFL and ATFL origins on the fibula were continuous and measured 3.48 +/- 0.39
      cm(2). The CFL insertion on the calcaneus measured 2.68 +/- 0.20 cm(2). The CFL
      was found 27.1 +/- 1.0 mm posterior and superior from the peroneal tubercle.
      CONCLUSIONS: In presumably uninjured specimens, both the ATFL and its footprint
      on the talus were bifid. The CFL and ATFL origins have a single confluent
      footprint on the anterior border of the distal fibula. The CFL footprint on the
      calcaneus is almost 3 cm posterior and superior to the peroneal tubercle.
      CLINICAL RELEVANCE: This study may assist surgeons in anatomically reconstructing
      the lateral ligament complex of the ankle.

PMID- 23559617
TI  - A complication due to shock wave therapy resembling calcaneal stress fracture.

PMID- 23559618
TI  - Multiple schwannomas of the posterior tibial nerve: a case series.

PMID- 23559619
TI  - Comment on "compression screw fixation of the syndesmosis".

PMID- 23559620
TI  - Comment on "compression screw fixation of the syndesmosis". Author reply.

PMID- 23559623
TI  - Musculoskeletal ultrasound for preoperative imaging of the plantar plate: a
      prospective analysis.
AB  - The purpose of this study was to prospectively compare preoperative findings on
      musculoskeletal ultrasound evaluation to observed intraoperative findings for
      patients undergoing surgical correction of plantar plate tears. Fifty consecutive
      patients with forefoot pain and a suspected unilateral plantar plate tear at the
      second metatarsophalangeal (MTP) joint were identified. The same examiner
      performed a 2-plane (longitudinal and transverse) musculoskeletal ultrasound on
      the painful second MTP joint. The contralateral second MTP joint was used for
      comparison. Longitudinal ultrasound images were graded as "torn" or "intact."
      Transverse ultrasound images were used to localize the suspected pathology.
      Results of the ultrasound were compared with observed intraoperative pathology.
      Forty-five plantar plate tears were identified intraoperatively. Longitudinal
      ultrasound images correctly identified 40 plantar plate tears. The longitudinal
      ultrasound had a sensitivity of 91.1%, a specificity of 25%, a positive
      predictive value of 91.1%, and a negative predictive value of 25%. Transverse
      ultrasound images identified 36 plantar plate tears correctly localizing only 19
      tears. Musculoskeletal ultrasound has been widely used to identify and localize
      pathology in many soft tissue structures. Whereas the longitudinal ultrasound
      images were useful in identifying plantar plate tears, the same cannot be said
      about the ability to localize the tear on the transverse ultrasound images.
      Therefore, ultrasound may not be as good an imaging modality as magnetic
      resonance imaging for identification and localization of plantar plate pathology.

PMID- 23559624
TI  - Chemerin connects fat to arterial contraction.
AB  - OBJECTIVE: Obesity and hypertension are comorbid in epidemic proportion, yet
      their biological connection is largely a mystery. The peptide chemerin is a
      candidate for connecting fat deposits around the blood vessel (perivascular
      adipose tissue) to arterial contraction. We presently tested the hypothesis that
      chemerin is expressed in perivascular adipose tissue and is vasoactive,
      supporting the existence of a chemerin axis in the vasculature. APPROACH AND
      RESULTS: Real-time polymerase chain reaction, immunohistochemistry, and Western
      analyses supported the synthesis and expression of chemerin in perivascular
      adipose tissue, whereas the primary chemerin receptor ChemR23 was expressed both
      in the tunica media and endothelial layer. The ChemR23 agonist chemerin-9 caused
      receptor, concentration-dependent contraction in the isolated rat thoracic aorta,
      superior mesenteric artery, and mesenteric resistance artery, and contraction was
      significantly amplified (more than 100%) when nitric oxide synthase was inhibited
      and the endothelial cell mechanically removed or tone was placed on the arteries.
      The novel ChemR23 antagonist CCX832 inhibited phenylephrine-induced and
      prostaglandin F2alpha-induced contraction (+perivascular adipose tissue),
      suggesting that endogenous chemerin contributes to contraction. Arteries from
      animals with dysfunctional endothelium (obese or hypertensive) demonstrated a
      pronounced contraction to chemerin-9. Finally, mesenteric arteries from obese
      humans demonstrate amplified contraction to chemerin-9. CONCLUSIONS: These data
      support a new role for chemerin as an endogenous vasoconstrictor that operates
      through a receptor typically attributed to function only in immune cells.

PMID- 23559625
TI  - Dietary carnosine prevents early atherosclerotic lesion formation in
      apolipoprotein E-null mice.
AB  - OBJECTIVE: Atherosclerotic lesions are associated with the accumulation of
      reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde
      metabolism has been shown to exacerbate atherosclerosis and enhance the
      accumulation of aldehyde-modified proteins in atherosclerotic plaques, no
      therapeutic interventions have been devised to prevent aldehyde accumulation in
      atherosclerotic lesions. APPROACH AND RESULTS: We examined the efficacy of
      carnosine, a naturally occurring beta-alanyl-histidine dipeptide, in preventing
      aldehyde toxicity and atherogenesis in apolipoprotein E-null mice. In vitro,
      carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes.
      Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the
      formation of free aldehydes 4-hydroxynonenal and malonaldialdehyde in Cu(2+)
      oxidized low-density lipoprotein. Preloading bone marrow-derived macrophages with
      cell-permeable carnosine analogs reduced 4-hydroxynonenal-induced apoptosis. Oral
      supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation
      in aortic valves of apolipoprotein E-null mice and attenuated the accumulation of
      protein-acrolein, protein-4-hydroxyhexenal, and protein-4-hydroxynonenal adducts
      in atherosclerotic lesions, whereas urinary excretion of aldehydes as carnosine
      conjugates was increased. CONCLUSIONS: The results of this study suggest that
      carnosine inhibits atherogenesis by facilitating aldehyde removal from
      atherosclerotic lesions. Endogenous levels of carnosine may be important
      determinants of atherosclerotic lesion formation, and treatment with carnosine or
      related peptides could be a useful therapy for the prevention or the treatment of
      atherosclerosis.

PMID- 23559626
TI  - Antithrombotic effect of antisense factor XI oligonucleotide treatment in
      primates.
AB  - OBJECTIVE: During coagulation, factor IX (FIX) is activated by 2 distinct
      mechanisms mediated by the active proteases of either FVIIa or FXIa. Both
      coagulation factors may contribute to thrombosis; FXI, however, plays only a
      limited role in the arrest of bleeding. Therefore, therapeutic targeting of FXI
      may produce an antithrombotic effect with relatively low hemostatic risk.
      APPROACH AND RESULTS: We have reported that reducing FXI levels with FXI
      antisense oligonucleotides produces antithrombotic activity in mice, and that
      administration of FXI antisense oligonucleotides to primates decreases
      circulating FXI levels and activity in a dose-dependent and time-dependent
      manner. Here, we evaluated the relationship between FXI plasma levels and
      thrombogenicity in an established baboon model of thrombosis and hemostasis. In
      previous studies with this model, antibody-induced inhibition of FXI produced
      potent antithrombotic effects. In the present article, antisense oligonucleotides
      mediated reduction of FXI plasma levels by >= 50% resulted in a demonstrable and
      sustained antithrombotic effect without an increased risk of bleeding.
      CONCLUSIONS: These results indicate that reducing FXI levels using antisense
      oligonucleotides is a promising alternative to direct FXI inhibition, and that
      targeting FXI may be potentially safer than conventional antithrombotic therapies
      that can markedly impair primary hemostasis.

PMID- 23559628
TI  - Walking versus running for hypertension, cholesterol, and diabetes mellitus risk
      reduction.
AB  - OBJECTIVE: To test whether equivalent energy expenditure by moderate-intensity
      (eg, walking) and vigorous-intensity exercise (eg, running) provides equivalent
      health benefits. APPROACH AND RESULTS: We used the National Runners' (n=33 060)
      and Walkers' (n=15 945) Health Study cohorts to examine the effect of differences
      in exercise mode and thereby exercise intensity on coronary heart disease (CHD)
      risk factors. Baseline expenditure (metabolic equivant hours per day [METh/d])
      was compared with self-reported, physician-diagnosed incident hypertension,
      hypercholesterolemia, diabetes mellitus, and CHD during 6.2 years follow-up.
      Running significantly decreased the risks for incident hypertension by 4.2%
      (P<10(-7)), hypercholesterolemia by 4.3% (P<10(-14)), diabetes mellitus by 12.1%
      (P<10(-5)), and CHD by 4.5% per METh/d (P=0.05). The corresponding reductions for
      walking were 7.2% (P<10(-6)), 7.0% (P<10(-8)), 12.3% (P<10(-4)), and 9.3%
      (P=0.01). Relative to <1.8 METh/d, the risk reductions for 1.8 to 3.6, 3.6 to
      5.4, 5.4 to 7.2, and >=7.2 METh/d were as follows: (1) 10.1%, 17.7%, 25.1%, and
      34.9% from running and 14.0%, 23.8%, 21.8%, and 38.3% from walking for
      hypercholesterolemia; (2) 19.7%, 19.4%, 26.8%, and 39.8% from running and 14.7%,
      19.1%, 23.6%, and 13.3% from walking for hypertension; and (3) 43.5%, 44.1%,
      47.7%, and 68.2% from running, and 34.1%, 44.2% and 23.6% from walking for
      diabetes mellitus (walking >5.4 METh/d excluded for too few cases). The risk
      reductions were not significantly different for running than walking for diabetes
      mellitus (P=0.94), hypertension (P=0.06), or CHD (P=0.26), and only marginally
      greater for walking than running for hypercholesterolemia (P=0.04). CONCLUSIONS:
      Equivalent energy expenditures by moderate (walking) and vigorous (running)
      exercise produced similar risk reductions for hypertension, hypercholesterolemia,
      diabetes mellitus, and possibly CHD.

PMID- 23559627
TI  - ABCA1 mediates unfolding of apolipoprotein AI N terminus on the cell surface
      before lipidation and release of nascent high-density lipoprotein.
AB  - OBJECTIVE: To gain insight into the mechanism by which ABCA1 generates nascent
      high-density lipoprotein. APPROACH AND RESULTS: HEK293 cells were stably
      transfected with ABCA1 vectors, encoding wild type, and the W590S and C1477R
      Tangier disease mutation isoforms, along with the K939M ATP-binding domain
      mutant. Apolipoprotein AI (ApoAI) binding, plasma membrane remodeling,
      cholesterol efflux, apoAI cell surface unfolding, and apoAI cell surface
      lipidation were determined, the latter 2 measured using novel fluorescent apoAI
      indicators. The W590S isoform had decreased plasma membrane remodeling and lipid
      efflux activities, and the C1477R isoform had decreased apoAI binding, and lipid
      efflux activities, whereas the K939M isoform did not bind apoAI, remodel the
      membrane, or efflux cholesterol. However, all ABCA1 isoforms led to apoAI
      unfolding at the cell surface, which was higher for the isoforms that increased
      apoAI binding. ApoAI lipidation was not detected on ABCA1-expressing cells, only
      in the conditioned medium, consistent with rapid release of nascent high-density
      lipoprotein from ABCA1-expressing cells. CONCLUSIONS: We identified a third
      activity of ABCA1, the ability to unfold the N terminus of apoAI on the cell
      surface. Our results support a model in which unfolded apoAI on the cell surface
      is an intermediate in its lipidation and that, once apoAI is lipidated, it forms
      an unstable structure that is rapidly released from the cells to generate high
      density lipoprotein.

PMID- 23559630
TI  - Transintestinal cholesterol excretion is an active metabolic process modulated by
      PCSK9 and statin involving ABCB1.
AB  - OBJECTIVE: Transintestinal cholesterol excretion (TICE) is an alternate pathway
      to hepatobiliary secretion. Our study aimed at identifying molecular mechanisms
      of TICE. APPROACH AND RESULTS: We studied TICE ex vivo in mouse and human
      intestinal explants, and in vivo after bile diversion and intestinal cannulation
      in mice. We provide the first evidence that both low-density lipoprotein (LDL)
      and high-density lipoprotein deliver cholesterol for TICE in human and mouse
      jejunal explants at the basolateral side. Proprotein convertase subtilisin kexin
      type 9 (PCSK9)(-/-) mice and intestinal explants show increased LDL-TICE, and
      acute injection of PCSK9 decreases TICE in vivo, suggesting that PCSK9 is a
      repressor of TICE. The acute repression was dependent on the LDL receptor (LDLR).
      Further, TICE was increased when mice were treated with lovastatin. These data
      point to an important role for LDLR in TICE. However, LDLR(-/-) mice showed
      increased intestinal LDL uptake, contrary to what is observed in the liver, and
      tended to have higher TICE. We interpret these data to suggest that there might
      be at least 2 mechanisms contributing to TICE; 1 involving LDL receptors and
      other unidentified mechanisms. Acute modulation of LDLR affects TICE, but chronic
      deficiency is compensated for most likely by the upregulation of the unknown
      mechanisms. Using mice deficient for apical multidrug active transporter ATP
      binding cassette transporter B1 a and b, and its inhibitor, we show that these
      apical transporters contribute significantly to TICE. CONCLUSIONS: TICE is
      operative in human jejunal explants. It is a metabolically active process that
      can be acutely regulated, inversely related to cholesterolemia, and
      pharmacologically activated by statins.

PMID- 23559631
TI  - Loss of function of parathyroid hormone receptor 1 induces Notch-dependent aortic
      defects during zebrafish vascular development.
AB  - OBJECTIVE: Coarctation of the aorta is rarely associated with known gene defects.
      Blomstrand chondrodysplasia, caused by mutations in the parathyroid hormone
      receptor 1 (PTHR1) is associated with coarctation of the aorta in some cases,
      although it is unclear whether PTHR1 deficiency causes coarctation of the aorta
      directly. The zebrafish allows the study of vascular development using approaches
      not possible in other models. We therefore examined the effect of loss of
      function of PTHR1 or its ligand parathyroid hormone-related peptide (PTHrP) on
      aortic formation in zebrafish. APPROACH AND RESULTS: Morpholino antisense
      oligonucleotide knockdown of either PTHR1 or PTHrP led to a localized occlusion
      of the mid-aorta in developing zebrafish. Confocal imaging of transgenic embryos
      showed that these defects were caused by loss of endothelium, rather than failure
      to lumenize. Using a Notch reporter transgenic ([CSL:Venus]qmc61), we found both
      PTHR1 and PTHrP knockdown-induced defective Notch signaling in the hypochord at
      the site of the aortic defect before onset of circulation, and the aortic
      occlusion was rescued by inducible Notch upregulation. CONCLUSIONS: Loss of
      function of either PTHR1 or PTHrP leads to a localized aortic defect that is
      Notch dependent. These findings may underlie the aortic defect seen in Blomstrand
      chondrodysplasia, and reveal a link between parathyroid hormone and Notch
      signaling during aortic development.

PMID- 23559629
TI  - mRNA-binding protein ZFP36 is expressed in atherosclerotic lesions and reduces
      inflammation in aortic endothelial cells.
AB  - OBJECTIVE: We studied the expression and function of an mRNA-binding protein,
      zinc finger protein-36 (ZFP36), in vascular endothelial cells in vivo and in
      vitro. We tested the hypotheses that ZFP36 regulates inflammation in vascular
      endothelial cells and that it functions through direct binding to target cytokine
      mRNAs. We also tested whether ZFP36 inhibits nuclear factor-kappaB-mediated
      transcriptional responses in vascular endothelial cells. APPROACH AND RESULTS:
      ZFP36 was minimally expressed in healthy aorta but was expressed in endothelial
      cells overlying atherosclerotic lesions in mice and humans. The protein was also
      expressed in macrophage foam cells of atherosclerosis. ZFP36 was expressed in
      human aortic endothelial cells in response to bacterial lipopolysaccharide,
      glucocorticoid, and forskolin, but not oxidized low-density lipoproteins or
      angiotensin II. Functional studies demonstrated that ZFP36 reduces the expression
      of inflammatory cytokines in target cells by 2 distinct mechanisms: ZFP36
      inhibits nuclear factor-kappaB transcriptional activation and also binds to
      cytokine mRNAs, leading to reduced transcript stability. CONCLUSIONS: ZFP36 is
      expressed in vascular endothelial cells and macrophage foam cells where it
      inhibits the expression of proinflammatory mRNA transcripts. The anti
      inflammatory effects of ZFP36 in endothelial cells occur via both transcriptional
      and posttranscriptional mechanisms. Our data suggest that enhancing vascular
      ZFP36 expression might reduce vascular inflammation.

PMID- 23559632
TI  - Diesel exhaust induces systemic lipid peroxidation and development of
      dysfunctional pro-oxidant and pro-inflammatory high-density lipoprotein.
AB  - OBJECTIVE: To evaluate whether exposure to air pollutants induces oxidative
      modifications of plasma lipoproteins, resulting in alteration of the protective
      capacities of high-density lipoproteins (HDLs). APPROACH AND RESULTS: We exposed
      apolipoprotein E-deficient mice to diesel exhaust (DE) at ~ 250 ug/m(3) for 2
      weeks, filtered air (FA) for 2 weeks, or DE for 2 weeks, followed by FA for 1
      week (DE+FA). DE led to enhanced lipid peroxidation in the brochoalveolar lavage
      fluid that was accompanied by effects on HDL functionality. HDL antioxidant
      capacity was assessed by an assay that evaluated the ability of HDL to inhibit
      low-density lipoprotein oxidation estimated by 2',7'-dichlorofluorescein
      fluorescence. HDL from DE-exposed mice exhibited 23,053 +/- 2844 relative
      fluorescence units, higher than FA-exposed mice (10,282 +/- 1135 relative
      fluorescence units, P<0.001) but similar to the HDL from DE+FA-exposed mice
      (22,448 +/- 3115 relative fluorescence units). DE effects on HDL antioxidant
      capacity were negatively correlated with paraoxonase enzymatic activity, but
      positively correlated with levels of plasma 8-isoprostanes, 12
      hydroxyeicosatetraenoic acid, 13-hydroxyoctadecadienoic acid, liver
      malondialdehyde, and accompanied by perturbed HDL anti-inflammatory capacity and
      activation of the 5-lipoxygenase pathway in the liver. CONCLUSIONS: DE emissions
      induced systemic pro-oxidant effects that led to the development of dysfunctional
      HDL. This may be one of the mechanisms by which air pollution contributes to
      enhanced atherosclerosis.

PMID- 23559634
TI  - Characterization of levels and cellular transfer of circulating lipoprotein-bound
      microRNAs.
AB  - OBJECTIVE: MicroRNAs are important intracellular regulators of gene expression,
      but also circulate in the blood being protected by extracellular vesicles,
      proteins, or high-density lipoprotein (HDL). Here, we evaluate the regulation and
      potential function of HDL- and low-density lipoprotein-bound miRs isolated from
      healthy subjects and patients with coronary artery disease. APPROACH AND RESULTS:
      HDL-bound miRs with known effects in the cardiovascular system were analyzed in
      HDL isolated from healthy subjects (n=10), patients with stable coronary artery
      disease (n=10), and patients with an acute coronary syndrome (n=10). In HDL from
      healthy subjects, miR-223 was detected at concentrations >10 000 copies/ug HDL,
      and miR-126 and miR-92a at about 3000 copies/ug HDL. Concentrations of most miRs
      were substantially higher in HDL as compared with low-density lipoprotein.
      However, HDL-bound miR-223 contributed to only 8% of the total circulating miRs.
      The signatures of miRs varied only slightly in HDL derived from patients with
      coronary artery disease. We did not observe a significant uptake of HDL-bound
      miRs into endothelial cells, smooth muscle cells, or peripheral blood mononuclear
      cells. However, patient-derived HDL transiently reduced miR expression
      particularly when incubated with smooth muscle and peripheral blood mononuclear
      cells. CONCLUSIONS: Circulating miRs are detected in HDL and to a lesser extent
      in low-density lipoprotein, and the miR-signatures are only slightly altered in
      patients with coronary artery disease. Lipoprotein-bound miRs were not
      efficiently delivered to endothelial, smooth muscle, and peripheral blood
      mononuclear cells suggesting that the lipoprotein-associated pool of miRs is not
      regulating the function of the studied cells in vitro.

PMID- 23559633
TI  - Anti-inflammatory and antiatherogenic role of BMP receptor II in endothelial
      cells.
AB  - OBJECTIVE: Atherosclerosis is an inflammatory disease with multiple underlying
      metabolic and physical risk factors. Bone morphogenic protein 4 (BMP4) expression
      is increased in endothelium in atherosclerosis-prone regions and is known to
      induce endothelial inflammation, endothelial dysfunction, and hypertension. BMP
      actions are mediated by 2 different types of BMP receptors (BMPRI and BMPRII).
      Here, we show a surprising finding that loss of BMPRII expression causes
      endothelial inflammation and atherosclerosis. APPROACH AND RESULTS: Using BMPRII
      siRNA and BMPRII(+/-) mice, we found that specific knockdown of BMPRII, but not
      other BMP receptors (Alk1, Alk2, Alk3, Alk6, ActRIIa, and ActRIIb), induced
      endothelial inflammation in a ligand-independent manner by mechanisms mediated by
      reactive oxygen species, nuclear factor-KappaB, and reduced nicotinamide adenine
      dinucleotide phosphate oxidases. Further, BMPRII(+/-)ApoE(-/-) mice developed
      accelerated atherosclerosis compared with BMPRII(+/+)ApoE(-/-) mice.
      Interestingly, we found that multiple proatherogenic stimuli, such as
      hypercholesterolemia, disturbed flow, prohypertensive angiotensin II, and the
      proinflammatory cytokine (tumor necrosis factor-alpha), downregulated BMPRII
      expression in endothelium, whereas antiatherogenic stimuli, such as stable flow
      and statin treatment, upregulated its expression in vivo and in vitro. Moreover,
      BMPRII expression was significantly diminished in human coronary advanced
      atherosclerotic lesions. Also, we were able to rescue the endothelial
      inflammation induced by BMPRII knockdown by overexpressing the BMPRII wild type,
      but not by the BMPRII short form lacking the carboxyl-terminal tail region.
      CONCLUSIONS: These results suggest that BMPRII is a critical, anti-inflammatory,
      and antiatherogenic protein that is commonly targeted by multiple pro- and
      antiatherogenic factors. BMPRII may be used as a novel diagnostic and therapeutic
      target in atherosclerosis.

PMID- 23559635
TI  - Targeting platelet GPIbbeta reduces platelet adhesion, GPIb signaling and
      thrombin generation and prevents arterial thrombosis.
AB  - OBJECTIVE: The glycoprotein (GP) Ib-V-IX complex regulates the adhesion,
      activation, and procoagulant activity of platelets. We previously reported that
      RAM.1, a rat monoclonal antibody directed against the extracellular domain of
      mouse GPIbbeta, diminished adhesion of platelets and chinese hamster ovary cells
      transfected with the human GPIb-IX complex to von Willebrand factor under flow
      conditions. Here, we further evaluated the functional importance of GPIbbeta by
      studying the impact of RAM.1 on GPIb-mediated platelet responses and in vitro and
      in vivo thrombus formation. APPROACH AND RESULTS: We show that RAM.1 dramatically
      reduced GPIb-mediated filopodia extension of chinese hamster ovary GPIb-IX cells
      after adhesion to von Willebrand factor. RAM.1 also reduced filopodia extension
      and GPIb-mediated Ca(2+) signaling after adhesion of mouse platelets to von
      Willebrand factor. RAM.1 inhibited thrombin generation in platelet-rich plasma
      without impairing phosphatidylserine exposure. In addition, RAM.1 reduced
      thrombus formation after perfusion of mouse whole blood over collagen in a shear
      dependent manner. This effect was confirmed in vivo, because injection of F(ab)'2
      fragments of RAM.1 diminished thrombus formation induced by laser beam injury of
      mesenteric arterioles and forceps injury of the abdominal aorta. In contrast,
      RAM.1 F(ab)'2 did not prolong the tail-bleeding time or increase the volume of
      blood lost. CONCLUSIONS: These findings are the first evidence that targeting a
      subunit other than GPIbalpha can lead to an antithrombotic effect via the GPIb-V
      IX complex. This could represent an alternative way to reduce thrombus formation
      with a minor impact on hemostasis.

PMID- 23559636
TI  - Hyperlipidemia attenuates vascular endothelial growth factor-induced
      angiogenesis, impairs cerebral blood flow, and disturbs stroke recovery via
      decreased pericyte coverage of brain endothelial cells.
AB  - OBJECTIVE: Therapeutic angiogenesis aims at the promotion of vascular growth,
      usually under conditions of atherosclerosis. It was unknown how hyperlipidemia, a
      risk factor that is closely associated with atherosclerosis of brain vessels in
      humans, influences vascular endothelial growth factor-induced angiogenesis and
      stroke recovery. APPROACH AND RESULTS: Wild-type and apolipoprotein-E (ApoE)(-/-)
      mice were kept on regular or cholesterol-rich diet for mimicking different
      severities of hyperlipidemia. Mice were treated intracerebroventricularly with
      recombinant human vascular endothelial growth factor for 21 days (0.02 ug/d) and
      subsequently subjected to 90-minute middle cerebral artery occlusion followed by
      1 or 24 hours of reperfusion. Histochemical, autoradiographic, and regional
      bioluminescence techniques were used to evaluate effects of blood lipids on
      postischemic angiogenesis, histopathologic brain injury, cerebral blood flow,
      protein synthesis and energy state, and pericyte coverage of brain endothelial
      cells. Hyperlipidemia dose-dependently attenuated vascular endothelial growth
      factor-induced capillary formation and pericyte coverage of brain endothelial
      cells, abolishing the improvement of cerebral blood flow during subsequent
      stroke, resulting in the loss of the metabolic penumbra and increased brain
      infarction. The enhanced angiogenesis after vascular endothelial growth factor
      treatment was accompanied by increased expression of the adhesion protein N
      cadherin, which mediates endothelial-pericytic interactions, in ischemic brain
      microvessels of wild-type mice on regular diet that was blunted in wild-type mice
      on Western diet and ApoE(-/-) mice on either diet. CONCLUSIONS: The compromised
      vessel formation and hemodynamics question the concept of therapeutic
      angiogenesis in ischemic stroke where hyperlipidemia is highly prevalent.

PMID- 23559637
TI  - Pattern recognition in bioinformatics.
AB  - Pattern recognition is concerned with the development of systems that learn to
      solve a given problem using a set of example instances, each represented by a
      number of features. These problems include clustering, the grouping of similar
      instances; classification, the task of assigning a discrete label to a given
      instance; and dimensionality reduction, combining or selecting features to arrive
      at a more useful representation. The use of statistical pattern recognition
      algorithms in bioinformatics is pervasive. Classification and clustering are
      often applied to high-throughput measurement data arising from microarray, mass
      spectrometry and next-generation sequencing experiments for selecting markers,
      predicting phenotype and grouping objects or genes. Less explicitly,
      classification is at the core of a wide range of tools such as predictors of
      genes, protein function, functional or genetic interactions, etc., and used
      extensively in systems biology. A course on pattern recognition (or machine
      learning) should therefore be at the core of any bioinformatics education
      program. In this review, we discuss the main elements of a pattern recognition
      course, based on material developed for courses taught at the BSc, MSc and PhD
      levels to an audience of bioinformaticians, computer scientists and life
      scientists. We pay attention to common problems and pitfalls encountered in
      applications and in interpretation of the results obtained. 

PMID- 23559639
TI  - A tool for RNA sequencing sample identity check.
AB  - SUMMARY: RNA sequencing data are becoming a major method of choice to study
      transcriptomes, including the mapping of gene expression quantitative trait loci
      (eQTLs). RNA sample contamination or swapping is a serious problem for downstream
      analysis and may result in false discovery and lose power to detect the true
      biological relationships. When genetic data are available, for example, in eQTL
      studies or samples have been previously genotyped or DNA sequenced, it is
      possible to combine genetic data and RNA-seq data to detect sample contamination
      and resolve sample swapping problems. In this article, we introduce a tool
      (IDCheck) that allows easy assessment of concordance between genotype (from SNP
      arrays or DNA sequencing) and gene expression (RNA-seq) samples. IDCheck compares
      the identity of RNA-seq reads and SNP genotypes using a likelihood-based method.
      Based on maximum likelihood estimates of relevant parameters, we can detect
      sample contamination and identify correct sample pairs when swapping occurs. Our
      tool provides an efficient and convenient way to evaluate and resolve these
      problems. AVAILABILITY: A complete description of the software is included on the
      application home page. The software is freely available in the public domain at
      http://eqtl.rc.fas.harvard.edu/idcheck/. SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 23559638
TI  - Bayesian hierarchical model of protein-binding microarray k-mer data reduces
      noise and identifies transcription factor subclasses and preferred k-mers.
AB  - MOTIVATION: Sequence-specific transcription factors (TFs) regulate the expression
      of their target genes through interactions with specific DNA-binding sites in the
      genome. Data on TF-DNA binding specificities are essential for understanding how
      regulatory specificity is achieved. RESULTS: Numerous studies have used universal
      protein-binding microarray (PBM) technology to determine the in vitro binding
      specificities of hundreds of TFs for all possible 8 bp sequences (8mers). We have
      developed a Bayesian analysis of variance (ANOVA) model that decomposes these
      8mer data into background noise, TF familywise effects and effects due to the
      particular TF. Adjusting for background noise improves PBM data quality and
      concordance with in vivo TF binding data. Moreover, our model provides
      simultaneous identification of TF subclasses and their shared sequence
      preferences, and also of 8mers bound preferentially by individual members of TF
      subclasses. Such results may aid in deciphering cis-regulatory codes and
      determinants of protein-DNA binding specificity. AVAILABILITY AND IMPLEMENTATION:
      Source code, compiled code and R and Python scripts are available from
      http://thebrain.bwh.harvard.edu/hierarchicalANOVA. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23559640
TI  - Detecting regulatory gene-environment interactions with unmeasured environmental
      factors.
AB  - MOTIVATION: Genomic studies have revealed a substantial heritable component of
      the transcriptional state of the cell. To fully understand the genetic regulation
      of gene expression variability, it is important to study the effect of genotype
      in the context of external factors such as alternative environmental conditions.
      In model systems, explicit environmental perturbations have been considered for
      this purpose, allowing to directly test for environment-specific genetic effects.
      However, such experiments are limited to species that can be profiled in
      controlled environments, hampering their use in important systems such as human.
      Moreover, even in seemingly tightly regulated experimental conditions, subtle
      environmental perturbations cannot be ruled out, and hence unknown environmental
      influences are frequent. Here, we propose a model-based approach to
      simultaneously infer unmeasured environmental factors from gene expression
      profiles and use them in genetic analyses, identifying environment-specific
      associations between polymorphic loci and individual gene expression traits.
      RESULTS: In extensive simulation studies, we show that our method is able to
      accurately reconstruct environmental factors and their interactions with genotype
      in a variety of settings. We further illustrate the use of our model in a real
      world dataset in which one environmental factor has been explicitly
      experimentally controlled. Our method is able to accurately reconstruct the true
      underlying environmental factor even if it is not given as an input, allowing to
      detect genuine genotype-environment interactions. In addition to the known
      environmental factor, we find unmeasured factors involved in novel genotype
      environment interactions. Our results suggest that interactions with both known
      and unknown environmental factors significantly contribute to gene expression
      variability. AVAILABILITY: and implementation: Software available at
      http://pmbio.github.io/envGPLVM/. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 23559641
TI  - International Journal of Toxicology. Editor's note.

PMID- 23559642
TI  - Preliminary nonclinical toxicity, pharmacokinetics, and pharmacodynamics of
      ALXN4100TPO, a thrombopoietin receptor agonist, in CD2F1 mice.
AB  - ALXN4100TPO, a thrombopoietin (TPO) receptor agonist, increases platelets,
      abrogates radiation-induced thrombocytopenia and affords significant survival
      benefit to lethally irradiated mice. This preliminary nonclinical safety study
      assessed effects of a single subcutaneous (sc) administration of ALXN4100TPO in
      CD2F1 mice randomized into naive, control antibody (ALXN4200, 100 mg/kg), low (1
      mg/kg), medium (10 mg/kg), or high (100 mg/kg) ALXN4100TPO doses. End points
      included clinical observations, body weight changes, hematology, histopathology,
      pharmacokinetics, pharmacodynamics by measuring platelet counts, and endogenous
      TPO (eTPO) levels. Salient findings were prominent increase in platelet counts
      and end cells of myeloid and lymphoid lineages; elevated megakaryopoiesis in bone
      marrow; and extramedullary hematopoiesis in spleen and liver. Serum ALXN4100TPO
      levels were maximum 24 hours after administration, with a half-life of 13 days.
      Endogenous TPO levels were elevated in 10 and 100 mg/kg ALXN4100TPO-treated
      groups. In conclusion, ALXN4100TPO (1-100 mg/kg, sc) treatment in CD2F1 mice
      resulted in profound pharmacological changes in the hematopoietic tissue;
      however, no life-threatening adverse events were observed.

PMID- 23559643
TI  - Toxicity of industrially relevant chlorinated organic solvents in vitro.
AB  - The cytotoxic effects of 4 industrially important chlorinated organic solvents,
      dichloromethane (DCM), 1,2-dichloroethane (DCE), trichloroethylene (TCE), and
      tetrachloroethylene (PERC) in vitro, were investigated. Jurkat T cells were
      exposed to the solvents individually for 72 hours and changes in reactive oxygen
      species (ROS) formation, cell proliferation, intracellular free calcium
      concentration ([Ca(2+)]), and caspase-3 activity were measured. There was a
      concentration-dependent increase in the ROS formation and intracellular free
      [Ca(2+)] following exposure to each of the solvents. This was accompanied by a
      decrease in the cell proliferation. Solvent potency decreased in the following
      order: PERC > TCE > DCM > DCE. Caspase-3 activity was increased in a
      concentration-dependent manner by TCE and PERC but was not significantly altered
      by DCM or DCE. n-Acetyl-l-cysteine pretreatment showed that changes in the
      intracellular free [Ca(2+)] and caspase-3 activity were independent of ROS
      formation. However, increased ROS formation did play a causal role in the
      decreased cell proliferation observed.

PMID- 23559644
TI  - Guillain-Barre syndrome in an adult patient with Henoch-Schonlein purpura.
AB  - A 42-year-old man presented with pain in the abdomen, massive haematemesis and
      rashes over the body and development of bilateral lower limb weakness the next
      day. The patient was later diagnosed with Guillain-Barre syndrome with Henoch
      Schonlein purpura. He was treated with intravenous immunoglobulins. At 3 months
      of follow-up and rehabilitation, patient showed complete recovery from weakness.

PMID- 23559645
TI  - A case of Takotsubo cardiomyopathy induced by accidental hypothermia and diabetic
      ketoacidosis.
AB  - Takotsubo cardiomyopathy is known to be triggered by some stress. We report the
      first case of Takotsubo cardiomyopathy induced by hypothermia and diabetic
      ketoacidosis (DKA). A 59-year-old woman was brought to our emergency department.
      Upon examination, she was found to be lethargic and disoriented. The body
      temperature was 30.9 degrees C, blood pressure was 86/68 mm Hg, blood glucose
      level was 1018 mg/dl. Urinalysis revealed the presence of ketones and arterial
      blood gas analysis revealed pH 6.87. She was diagnosed with DKA and accidental
      hypothermia. An ECG demonstrated a J wave (V(4-5)) and ST-segment elevation (V(3
      5)), and an ultrasound cardiogram revealed contractile failure of the left
      ventricular wall at the apex with hypercontraction of the basal segment. Coronary
      artery disease was ruled out by coronary angiography, and the diagnosis of
      Takotsubo cardiomyopathy was confirmed. Physicians should keep in mind that
      Takotsubo cardiomyopathy can be induced by accidental hypothermia and DKA.

PMID- 23559646
TI  - Endoscopic mucosal resection of an oesophageal carcinoid tumour.

PMID- 23559647
TI  - Non-operative therapy for pilonidal sinus in adolescence: crystallised phenol
      application, 'report of a case'.
AB  - Pilonidal sinus (PS) is an acquired disease at the sacrococcygeal region that can
      be treated by different surgical techniques. Crystallised phenol application
      seems to be an alternative therapy to surgery with higher success rates, lower
      costs, faster recovery and earlier return to work. We aimed to state the success
      of phenol application for PS in adolescence. A 14-year-old boy with recurrent PS,
      an 18-year-old girl with the history of pilonidal abscess and a 15-year-old girl
      with PS was hospitalised. All patients underwent phenol application in an
      outpatient setting. The patients were followed thereafter. The 14-year-old boy
      and 18-year-old girl did not face any problems and all sinuses healed completely.
      The 15-year-old girl was followed for 2 weeks because of intergluteal maceration
      and ongoing drainage. She underwent another phenol application and the course
      after intervention was uneventful with complete healing of the sinus.
      Crystallised phenol application seems to be a promising non-operative therapy for
      PS in adolescents.

PMID- 23559648
TI  - Andersson lesion in ankylosing spondylitis.
AB  - A middle-aged male patient developed acute back pain and a lumbar vertebral
      lesion following trivial physical trauma. The lesion was considered as
      tuberculous on vertebral x-rays and MRI. After biopsy of the lesion and spinal
      fixation, the patient was kept on empirical antituberculous treatment (ATT) to
      which he did not respond. On re-evaluation he was diagnosed to have an Andersson
      lesion in ankylosing spondylitis (AS). ATT was stopped and he was successfully
      managed by rest, steroids, methotrexate and sulfasalazine. A careful look at the
      patient's plain x-ray spine and awareness about the lesion can avoid misdiagnosis
      of this characteristic vertebral lesion found in AS.

PMID- 23559649
TI  - Blunt traumatic internal carotid artery dissection with delayed stroke in a young
      skydiver.
AB  - We describe a case of a 33-year-old skydiver who presented to the emergency
      department after a traumatic landing following a parachuting episode. He
      initially presented with right knee pain secondary to a tibial plateau fracture.
      There were no neurological symptoms or signs at the initial assessment. While he
      was still in the emergency department, he suddenly developed headache and left
      sided hemiplegia. An urgent work-up showed right middle cerebral artery
      thrombosis with right internal carotid thrombosis and dissection. We have
      discussed some possible mechanism of injury in skydiving that may have
      predisposed to the occurrence of cervical dissection in our patient.

PMID- 23559650
TI  - Multilocular cystic renal cell carcinoma: a rare entity.
AB  - Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon subtype of clear
      cell renal cell carcinoma that appears to have a favourable prognosis. Literature
      reports a very low incidence of 1-2% of MCRCC among the renal neoplasms. The
      first such reported case was in 1957 by Robinson. In 1998, Eble et al suggested
      following diagnostic criterion for MCRCC: (1) an expansile mass surrounded by a
      fibrous capsule; (2) interior of tumour entirely composed of cysts and septa with
      no expansile nodule or solid component confined to more than 10% of entire tumour
      and (3) septa containing aggregates of clear epithelial cells. We report a case
      of MCRCC in a 60-year-old male patient who presented with abdominal lump and
      after suspicion of renal malignancy underwent nephrectomy. The patient was
      perfectly well till last follow-up of 3 months postoperatively.

PMID- 23559651
TI  - Deep lobe parotid pleomorphic adenoma presenting as obstructive sleep apnoea.
AB  - We present a rare case of obstructive sleep apnoea (OSA) secondary to a deep lobe
      parotid pleomorphic adenoma and discuss its management, including the need for a
      thorough examination and multidisciplinary approach. Only a few cases of
      pleomorphic adenoma of the deep lobe of the parotid gland causing OSA have been
      reported. Our case is not only extremely rare but also highlights that key
      diagnoses maybe missed if a thorough assessment is not performed.

PMID- 23559652
TI  - Klebsiella pneumoniae liver abscess and endophthalmitis.
AB  - A 36-year-old man was referred to the general medical team with endophthalmitis.
      He was noted to have raised inflammatory markers and deranged liver function
      tests on admission. Subsequent abdominal ultrasound scan revealed a liver abscess
      requiring percutaneous drainage. A common human pathogen, Klebsiella pneumoniae,
      was cultured from multiple sites. K pneumoniae has virulent serotypes (K1 and K2)
      that can cause primary liver abscess with metastatic infections. Cases have
      previously been predominantly reported in Southeast Asia but are increasing in
      prevalence in Europe and North America. The main known risk factor for the
      disease is diabetes mellitus. Swift antibiotic therapy, ophthalmology review and
      percutaneous drainage of any liver abscess are essential. Early recognition of
      the syndrome, despite potentially few initial symptoms, can significantly reduce
      morbidity and mortality. The authors report the first recorded case of K
      pneumoniae liver abscess with endophthalmitis in the UK.

PMID- 23559653
TI  - Pelvic haemophilic pseudotumour in a patient with haemophilia.

PMID- 23559654
TI  - Retrodental synovial cyst: MRI findings.

PMID- 23559655
TI  - 64-MDCT can depict the thrombi expanded from the left lower pulmonary vein to the
      left atrium in the patient with angina pectoris.
AB  - Stroke is an important clinical problem and some strokes are caused by a cardiac
      thrombus. Although large thrombus in the left atrium (LA) is known, small-sized
      LA thrombus is rare. LA thrombus or a left atrial appendage (LAA) thrombus is
      well known to cause ischaemic stroke in patients with atrial fibrillation (AF).
      For patients with AF, anticoagulants are recommended to prevent stroke. 64-slice
      multidetector CT (64-MDCT) can estimate not only the coronary artery stenosis,
      but LAA thrombus and small pulmonary vein thrombus (PVT). This study demonstrated
      the thrombi in the left lower pulmonary vein to LA in a 70-year-old man without
      AF by 64-MDCT. The LA thrombi were identified by transthoracic echocardiography,
      the size of which was 30.2 mm*8.1 mm. PVT and the small LA thrombus seem to have
      been significantly underestimated. 64-MDCT is a useful tool to estimate PVT and
      LA thrombi promptly.

PMID- 23559656
TI  - The isolated fourth ventricle.
AB  - Isolated enlargement of the fourth ventricle, or 'encysted' fourth ventricle is a
      rare late complication following shunt insertion of the lateral ventricles for
      hydrocephalus. Caudal and rostral obstruction of the fourth ventricle and its
      subsequent dilation results in compression of adjacent cerebellum and brain stem
      structures; treatment with further shunt insertion directly to the fourth
      ventricle is invariably successful. There is potential for diagnostic delay, when
      clinical symptoms and signs of cerebellar and brain stem compromise are
      unrecognised or attributed to other factors, and attention on the CT is focused
      on the lateral ventricular system and the already existing ventriculoperitoneal
      shunt, which will appear unchanged from previous scans. We report two cases with
      isolated fourth ventricular obstruction and review the literature to highlight
      the importance of recognising this condition.

PMID- 23559657
TI  - Something fishy: an unusual Erysipelothrix rhusiopathiae infection in an
      immunocompromised individual.
AB  - A 39-year-old man with a history of Crohn's disease presented to the emergency
      department with a 12-h history of worsening febrile illness. He deteriorated
      rapidly with progression to sepsis and was admitted to the intensive care unit.
      Initial treatment comprised broad spectrum antibiotics and inotropic support
      resulting in rapid improvement. With the immunocompromised state of the patient,
      and multiple blood cultures revealing Erysipelothrix rhusiopathiae, a detailed
      history disclosed a recent injury sustained from a fishing wire as the probable
      source of an infection. Treatment was narrowed to target the identified pathogen,
      the patient made a full recovery, and was counselled to be more cautious in
      future fishing activities.

PMID- 23559658
TI  - Interpretation of CT imaging: a growing problem in times of obesity?

PMID- 23559659
TI  - Hereditary opalescent dentin.

PMID- 23559660
TI  - Papillon Lefevre syndrome.

PMID- 23559661
TI  - Septic shock caused by Elizabethkingia meningoseptica: a case report and review
      of literature.
AB  - A 70-year-old woman, resident of a nursing home presented with complaints of
      fever for 1 day. Initial history, physical examination and laboratory tests were
      consistent with the diagnosis of systemic inflammatory response syndrome; blood
      culture from peripheral and central perm catheter were sent. Patient was started
      on empiric antibiotics and aggressive hydration. Blood cultures from peripheral
      access and central perm catheter grew Elisabethkingia meningoseptica on the
      second day. Patient was transferred to the intensive care unit for septic shock
      where patient needed vasopressors. Antibiotics were switched to intravenous
      trimethoprim-sulfamethoxazole, perm catheter was removed and catheter tip culture
      was sent. Catheter tip grew E meningoseptica (45 colony forming units). Patient
      showed excellent treatment response to intravenous trimethoprim-sulfamethoxazole
      and was weaned off pressors on day 4 with uneventful stay afterwards.

PMID- 23559662
TI  - Differential stimulation of neurotrophin release by the biocompatible nano
      material (carbon nanotube) in primary cultured neurons.
AB  - In order to develop novel, effective therapies for central nervous system
      regeneration, it is essential to better understand the role of neurotrophic
      factors and to design, accordingly, better artificial scaffolds to support both
      neurite outgrowth and synapse formation. Both nerve growth factor and brain
      derived neurotrophic factor are major factors in neural survival, development,
      synaptogenesis, and synaptic connectivity of primary cultured neurons. As a prime
      candidate coating material for such neural cultures, carbon nanotubes offer
      unique structural, mechanical, and electrical properties. In this study, carbon
      nanotubes coated glass-coverslips were used as the matrix of a primary neural
      culture system used to investigate the effects of carbon nanotubes on neurite
      outgrowth and nerve growth factor/brain-derived neurotrophic factor release and
      expression. For these purposes, we performed comparative analyses of primary
      cultured neurons on carbon nanotubes coated, non-coated, and Matrigel-coated
      coverslips. The morphological findings showed definite carbon nanotubes effects
      on the neurite outgrowths and synaptogenic figures in both cortical and
      hippocampal neurons when compared with the non-coated negative control. Although
      the carbon nanotubes did not change neurotrophin expression levels, it stimulated
      brain-derived neurotrophic factor release into the media from both types of
      neurons. Accordingly, we suggest a different mechanism of action between carbon
      nanotubes and Matrigel in relation to the specific neurotrophic factors. Since
      carbon nanotubes supply long-term extracellular molecular cues for the survival
      and neurite outgrowths of cultured neurons, the results from this study will
      contribute to an understanding of carbon nanotubes biological effects and provide
      new insight into their role in the secretion of neurotrophic factors. 

PMID- 23559663
TI  - Online support for children with asthma and allergies.
AB  - Children with asthma and allergies experience social isolation and gaps in social
      support particularly from peers. The objective of this pilot study was to design
      and test an accessible online support intervention for these children. Children
      (n = 27) aged 7 to 11 from across Canada participated. GoToMeeting was employed
      for the support group sessions and Club Penguin for social connections during and
      between support group meetings. Content included: strategies for coping with
      asthma and allergies, role playing and games to help children deal with difficult
      situations, fun and enjoyment, and presentations by positive role models.
      Participation in the online peer support intervention was high, 86.3% on average
      over the 8-week intervention. By sharing their experiences, listening to peers'
      experiences, and role playing, children were introduced to practical skills:
      problem solving, communicating, seeking support, and self-advocacy.

PMID- 23559664
TI  - Functional limitations in older adults who have cognitive impairment without
      dementia.
AB  - OBJECTIVE: To characterize the prevalence of functional limitations among older
      adults with cognitive impairment without dementia (CIND). METHODS: Secondary data
      analysis was performed using the Aging, Demographics, and Memory Study data set.
      A total of 856 individuals aged >= 71 years were assigned to 3 diagnostic
      cognitive categories. A questionnaire was completed by a proxy informant
      regarding functional limitations for 744 of the 856 respondents. RESULTS: Of the
      744 patients, 263 (13.9%) had dementia, 201 (21.3%) had CIND, and 280 (64.8%) had
      normal cognition. Informants reported >=1 instrumental activities of daily living
      (ADLs) limitation in 45% of the patients with CIND compared to 13% of the
      patients with normal cognition and 85% of the patients with dementia (P < .001).
      The ADL impairments among individuals with CIND were primarily attributed to
      physical health problems (n = 41; 40%). CONCLUSIONS: Many individuals with CIND
      have impairment in a range of complex and basic daily activities, largely due to
      physical health problems.

PMID- 23559666
TI  - High adherence to a neuromuscular injury prevention programme (FIFA 11+) improves
      functional balance and reduces injury risk in Canadian youth female football
      players: a cluster randomised trial.
AB  - BACKGROUND: A protective effect on injury risk in youth sports through
      neuromuscular warm-up training routines has consistently been demonstrated.
      However, there is a paucity of information regarding the quantity and quality of
      coach-led injury prevention programmes and its impact on the physical performance
      of players. OBJECTIVE: The aim of this cluster-randomised controlled trial was to
      assess whether different delivery methods of an injury prevention programme (FIFA
      11+) to coaches could improve player performance, and to examine the effect of
      player adherence on performance and injury risk. METHOD: During the 2011 football
      season (May-August), coaches of 31 tiers 1-3 level teams were introduced to the
      11+ through either an unsupervised website or a coach-focused workshop with and
      without additional on-field supervisions. Playing exposure, adherence to the 11+,
      and injuries were recorded for female 13-year-old to 18-year-old players.
      Performance testing included the Star Excursion Balance Test (SEBT), single-leg
      balance, triple hop and jumping-over-a-bar tests. RESULTS: Complete preseason and
      postseason performance tests were available for 226 players (66.5%). Compared to
      the unsupervised group, single-leg balance (OR=2.8; 95% CI 1.1 to 4.6) and the
      anterior direction of the SEBT improved significantly in the onfield supervised
      group of players (OR=4.7; 95% CI 2.2 to 7.1), while 2-leg jumping performance
      decreased (OR=-5.1; 95% CI -9.9 to -0.2). However, significant improvements in 5
      of 6 reach distances in the SEBT were found, favouring players who highly adhered
      to the 11+. Also, injury risk was lower for those players (injury rate ratio,
      IRR=0.28, 95% CI 0.10 to 0.79). CONCLUSIONS: Different delivery methods of the
      FIFA 11+ to coaches influenced players' physical performance minimally. However,
      high player adherence to the 11+ resulted in significant improvements in
      functional balance and reduced injury risk.

PMID- 23559667
TI  - Foreign-born Latino men subgroups: the case of mislabel identity.

PMID- 23559668
TI  - Function and expression of ATIP and its variants in cardiomyoblast cell line
      H9c2.
AB  - HYPOTHESIS: Cardiac hypertrophy in myocytes is in part regulated by changes in
      expression of a novel Ang II type 2 receptor (AT2-receptor) interacting protein
      identified as ATIP. INTRODUCTION: The role of the AT2-receptor in cardiac
      hypertrophy is controversial, with some reports indicating that AT2-receptor
      activation has detrimental effects on disease progression, whereas others
      indicate that it has a beneficial role. MATERIALS AND METHODS: In an effort to
      unravel this paradox, we examined the expression and function of ATIP in cell
      based models of cardiac hypertrophy using QPCR, immunohistochemistry, cell
      proliferation, morphological and transfection techniques in H9c2 cardio-myoblast
      and myotubules. RESULTS: These studies indicate that in cultured cardio-myoblast
      and myotubules, Ang II mediates cellular hypertrophy and proliferation solely via
      the AT1-receptor, the ATIP variants are abundantly expressed and that ATIP3 may
      play an anti-proliferative/hypertrophic role in these cells in the absence of AT2
      receptor expression or activation. CONCLUSIONS: Previously ATIP has been shown to
      inhibit growth factor signalling in cancerous cells via an interaction with the
      AT2-receptor. This is the first report to identify that ATIP may have a similar
      role in other disease states characterised by excessive growth and indicates that
      for ATIP3, at least, an interaction with the AT2-receptor may not be necessary.

PMID- 23559670
TI  - I've got that under my skin!

PMID- 23559669
TI  - Rituximab treatment for 'rhupus syndrome': clinical and power-Doppler
      ultrasonographic monitoring of response. A longitudinal pilot study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of rituximab in patients suffering
      from rhupus unresponsive to therapy with non-biological disease-modifying anti
      rheumatic drugs (DMARDs). METHODS: Six patients fulfilling criteria for both
      rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and with a DAS28
      score >5.1 were enrolled to receive two fortnightly 1000 mg rituximab doses at
      baseline and after 28 weeks. All patients underwent clinical, laboratory, and
      power- Doppler (PD) ultrasonographic (US) assessment at baseline and after 14, 28
      and 56 weeks. RESULTS: A sustained improvement in DAS28, SLEDAI, HAQ, laboratory
      markers and ultrasound indices together with a significant reduction in the daily
      dose of prednisone were observed throughout follow-up. CONCLUSION: Rituximab may
      be a safe and effective therapeutic option in refractory rhupus patients.

PMID- 23559673
TI  - Mitochondria oxidative stress, connexin43 remodeling, and sudden arrhythmic
      death.
AB  - BACKGROUND: Previously, we showed that a mouse model (ACE8/8) of cardiac renin
      angiotensin system activation has a high rate of spontaneous ventricular
      tachycardia and sudden cardiac death secondary to a reduction in connexin43
      level. Angiotensin-II activation increases reactive oxygen species (ROS)
      production, and ACE8/8 mice show increased cardiac ROS. We sought to determine
      the source of ROS and whether ROS played a role in the arrhythmogenesis. METHODS
      AND RESULTS: Wild-type and ACE8/8 mice with and without 2 weeks of treatment with
      L-NIO (NO synthase inhibitor), sepiapterin (precursor of tetrahydrobiopterin),
      MitoTEMPO (mitochondria-targeted antioxidant), TEMPOL (a general antioxidant),
      apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor),
      allopurinol (xanthine oxidase inhibitor), and ACE8/8 crossed with P67 dominant
      negative mice to inhibit the nicotinamide adenine dinucleotide phosphate oxidase
      were studied. Western blotting, detection of mitochondrial ROS by MitoSOX Red,
      electron microscopy, immunohistochemistry, fluorescent dye diffusion technique
      for functional assessment of connexin43, telemetry monitoring, and in vivo
      electrophysiology studies were performed. Treatment with MitoTEMPO reduced sudden
      cardiac death in ACE8/8 mice (from 74% to 18%; P<0.005), decreased spontaneous
      ventricular premature beats, decreased ventricular tachycardia inducibility (from
      90% to 17%; P<0.05), diminished elevated mitochondrial ROS to the control level,
      prevented structural damage to mitochondria, resulted in 2.6-fold increase in
      connexin43 level at the gap junctions, and corrected gap junction conduction.
      None of the other antioxidant therapies prevented ventricular tachycardia and
      sudden cardiac death in ACE8/8 mice. CONCLUSIONS: Mitochondrial oxidative stress
      plays a central role in angiotensin II-induced gap junction remodeling and
      arrhythmia. Mitochondria-targeted antioxidants may be effective antiarrhythmic
      drugs in cases of renin-angiotensin system activation.

PMID- 23559674
TI  - Pulmonary vein isolation using a visually guided laser balloon catheter: the
      first 200-patient multicenter clinical experience.
AB  - BACKGROUND: Because of the technical difficulty with achieving pulmonary vein
      (PV) isolation in the treatment of patients with paroxysmal atrial fibrillation,
      novel catheter designs to facilitate the procedure are in development. A visually
      guided laser ablation (VGLA) catheter was designed to allow the operator to
      directly visualize target tissue for ablation and then deliver laser energy to
      perform point-to-point circumferential ablation. Single-center studies have
      demonstrated favorable safety and efficacy. We sought to determine the
      multicenter feasibility, efficacy, and safety of performing PV isolation using
      the VGLA catheter. METHODS AND RESULTS: This study includes the first 200
      paroxysmal atrial fibrillation patients treated with the VGLA catheter (33
      operators, 15 centers). After transseptal puncture, the VGLA catheter was used to
      perform PV isolation. Electric isolation was assessed using a circular mapping
      catheter. Using the VGLA catheter, 98.8% (95% confidence interval, 97.8%-99.5%)
      of targeted PVs were isolated using a mean of 1.07 catheters per patient.
      Fluoroscopy and procedure times were 31+/-21 (mean+/-SD) and 200+/-54 minutes,
      respectively, and improved with operator experience. There were no instances of
      stroke, transient ischemic attack, atrioesophageal fistulas, or significant PV
      stenosis. There was a 2% incidence of cardiac tamponade and a 2.5% incidence of
      phrenic nerve palsy. At 12 months, the drug-free rate of freedom from atrial
      arrhythmias after 1 or 2 procedures was 60.2% (95% confidence interval, 52.7%
      67.4%). CONCLUSIONS: In this multicenter experience of the first 200 patients
      treated with the VGLA catheter, PV isolation can be achieved in virtually all
      patients using a single VGLA catheter with an efficacy similar to radiofrequency
      ablation.

PMID- 23559675
TI  - MicroRNA-93 controls perfusion recovery after hindlimb ischemia by modulating
      expression of multiple genes in the cell cycle pathway.
AB  - BACKGROUND: MicroRNAs are key regulators of gene expression in response to
      injury, but there is limited knowledge of their role in ischemia-induced
      angiogenesis, such as in peripheral arterial disease. Here, we used an unbiased
      strategy and took advantage of different phenotypic outcomes that follow
      surgically induced hindlimb ischemia between inbred mouse strains to identify key
      microRNAs involved in perfusion recovery from hindlimb ischemia. METHODS AND
      RESULTS: From comparative microRNA profiling between inbred mouse strains that
      display profound differences in their extent of perfusion recovery after hindlimb
      ischemia, we found that the mouse strain with higher levels of microRNA-93 (miR
      93) in hindlimb muscle before ischemia and the greater ability to upregulate miR
      93 in response to ischemia had better perfusion recovery. In vitro,
      overexpression of miR-93 attenuated hypoxia-induced apoptosis in both endothelial
      and skeletal muscle cells and enhanced proliferation in both cell types. In
      addition, miR-93 overexpression enhanced endothelial cell tube formation. In
      vivo, miR-93 overexpression enhanced capillary density and perfusion recovery
      from hindlimb ischemia, and antagomirs to miR-93 attenuated perfusion recovery.
      Both in vitro and in vivo modulation of miR-93 resulted in alterations in the
      expression of >1 cell cycle pathway gene in 2 different cell types. CONCLUSIONS:
      Our data indicate that miR-93 enhances perfusion recovery from hindlimb ischemia
      by modulation of multiple genes that coordinate the functional pathways of cell
      proliferation and apoptosis. Thus, miR-93 is a strong potential target for
      pharmacological modulation to promote angiogenesis in ischemic tissue.

PMID- 23559676
TI  - The skeletal consequences of growth hormone therapy in dialyzed children: a
      randomized trial.
AB  - BACKGROUND AND OBJECTIVE: The effects of recombinant human growth hormone on
      renal osteodystrophy are unknown; thus, the effects of growth hormone (GH) on
      bone histomorphometry were assessed in pediatric patients with ESRD. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-three patients who underwent bone
      biopsy between July 1994 and May 1999 were randomly assigned to therapy with or
      without GH. Patients were stratified by bone formation rate; all patients with
      high bone turnover received intraperitoneal calcitriol. Serum biochemical values
      were obtained monthly, and bone biopsy was repeated after 8 months. RESULTS:
      Median patient age was 11.7 years (interquartile range [IQR], 7.6, 14.1 years);
      45% of patients were male, and 52% were prepubertal. Median dialysis duration was
      0.4 (IQR, 0.3, 0.8) year. Bone formation rate per bone surface increased from
      15.0 (9.6, 21.8) to 154.6 (23.7, 174.3) MUm(2)/MUm(3) per year (P=0.05) in
      patients with low bone turnover treated with GH, decreased from 103.3 (57.0,
      173.4) to 60.3 (20.3, 13.7) MUm(2)/MUm(3) per year in patients with high bone
      turnover receiving standard therapy (P=0.03), and was unchanged in the other two
      groups. Bone formation rates were higher with GH, irrespective of underlying bone
      histologic features (P=0.05). Parathyroid hormone did not differ between groups.
      GH therapy resulted in greater increases in height SD scores (estimated mean
      difference in change +/- SD, 0.324+/-0.076; P<0.001), irrespective of underlying
      bone histologic features. CONCLUSIONS: GH therapy improves height in pediatric
      dialysis patients, irrespective of underlying bone histologic features. Bone
      formation rates are higher in GH recipients, and GH therapy alters the
      relationship between circulating parathyroid hormone values and bone turnover.

PMID- 23559678
TI  - American Society of Nephrology quiz and questionnaire 2012: renal replacement
      therapy.
AB  - Presentation of the Nephrology Quiz and Questionnaire has become an annual
      tradition at the meetings of the American Society of Nephrology. It is a very
      popular session judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time, using
      audience response devices, with the answers of program directors of nephrology
      training programs in the United States acquired through an Internet-based
      questionnaire. Topics presented here include fluid and electrolyte disorders,
      glomerular diseases, transplantation, and ESRD and dialysis. Cases representing
      each of these categories along with single best answer questions were prepared by
      a panel of experts (Drs. Palmer, Fervenza, and Brennan and Mehrotra,
      respectively). The correct and incorrect answers then were briefly discussed
      after the audience responses, and the results of the questionnaire were
      displayed. This article tries to recapitulate the session and reproduce its
      educational value for a larger audience-the readers of the CJASN. 

PMID- 23559677
TI  - Vascular and renal hemodynamic changes after renal denervation.
AB  - BACKGROUND AND OBJECTIVES: Renal denervation (RDN) has been shown to be effective
      in reducing BP in treatment-resistant hypertension. Measurement of the renal and
      sympathetic activity revealed a decrease in sympathetic drive to the kidney and
      small resistance vessels after RDN. However, the consequences on renal perfusion
      and renal vascular resistance (RVR), as well as central hemodynamics, are
      unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Nineteen patients with
      treatment-resistant hypertension (office BP>=140/90 mmHg, despite at least three
      antihypertensive drugs [including a diuretic], and diagnosis confirmed by 24-hour
      ambulatory BP monitoring) underwent RDN between January and October 2011. Renal
      perfusion and RVR were noninvasively assessed by magnetic resonance imaging with
      arterial spin labeling, and renal function was assessed by estimating GFR before
      (day -1), after (day +1), and again after 3 months of RDN. Central hemodynamics
      was assessed using pulse wave analysis at day -1 and after 6 months of RDN.
      RESULTS: Peripheral office BP (systolic, 158+/-26 versus 142+/-23 mmHg, P=0.002;
      diastolic, 83+/-13 versus 76+/-9 mmHg, P=0.02) and mean systolic 24-hour
      ambulatory BP (159+/-17 versus 152+/-17 mmHg, P=0.02) were significantly reduced
      6 months after RDN. Renal perfusion was not statistically different between day 
      1 and day +1 (256.8 [interquartile range (IQR), 241-278] versus 263.4 [IQR, 252
      277] ml/min per 100 g; P=0.17) as well as after 3 months (256.8 [IQR, 241-278]
      versus 261.2 [IQR, 240-285] ml/min per 100 g; P=0.27) after RDN. RVR dropped
      (432.1 [IQR, 359-525] versus 390.6 [IQR, 338-461] AU; P=0.02), whereas renal
      function was not statistically different at any time point. Central systolic BP
      (145+/-31 versus 131+/-28 mmHg; P=0.009), diastolic BP (85+/-18 versus 80+/-14
      mmHg; P=0.03), and central pulse pressure (61+/-18 versus 52+/-18 mmHg; P=0.02)
      were significantly reduced 6 months after RDN. Central augmentation index (24+/-8
      versus 20+/-8%; P=0.02) was decreased 6 months after RDN. CONCLUSION: The data
      indicate that RDN significantly reduced peripheral and central BP. Despite
      reduced systemic BP, renal perfusion and function did not change after RDN.

PMID- 23559679
TI  - Future of Medicare immunosuppressive drug coverage for kidney transplant
      recipients in the United States.
AB  - Kidney transplantation is the preferred treatment for patients with ESRD. It
      improves the quality of life in recipients, increases patient survival, and is
      also substantially less costly than maintenance dialysis. Long-term transplant
      success requires immunosuppressant drug therapy for the life of the allograft.
      Under current law, Medicare coverage for most recipients (except for those
      recipients over 65 years of age or with nonkidney-related disabilities) lasts
      only 3 years, leaving many recipients unable to afford these medications. Lack of
      drug therapy often leads to allograft rejection, resulting in premature graft
      failure, return to dialysis, or death. This article reviews the current policy
      for Medicare immunosuppressive drug coverage and analyzes the potential impact of
      pending legislative proposals H.R. 2969 and S. 1454 and the Patient Protection
      and Affordable Care Act. 

PMID- 23559680
TI  - Candidate gene analysis of arteriovenous fistula failure in hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Arteriovenous fistula (AVF) failure remains an
      important cause of morbidity in hemodialysis patients. The exact underlying
      mechanisms responsible for AVF failure are unknown but processes like
      proliferation, inflammation, vascular remodeling, and thrombosis are thought to
      be involved. The current objective was to investigate the association between AVF
      failure and single nucleotide polymorphisms (SNPs) in genes related to these
      pathophysiologic processes in a large population of incident hemodialysis
      patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 479 incident
      hemodialysis patients were included between January 1997 and April 2004. Follow
      up lasted 2 years or until AVF failure, defined as surgery, percutaneous
      endovascular intervention, or abandonment of the vascular access. Forty-three
      SNPs in 26 genes, related to proliferation, inflammation, endothelial function,
      vascular remodeling, coagulation, and calcium/phosphate metabolism, were
      genotyped. Relations were analyzed using Cox regression analysis. RESULTS: In
      total, 207 (43.2%) patients developed AVF failure. After adjustment, two SNPs
      were significantly associated with an increased risk of AVF failure. The hazard
      ratio (95% confidence interval) of LRP1 rs1466535 was 1.75 (1.15 to 2.66) and
      patients with factor V Leiden had a hazard ratio of 2.54 (1.41 to 4.56) to
      develop AVF failure. The other SNPs were not associated with AVF failure.
      CONCLUSIONS: In this large cohort of hemodialysis patients, only 2 of the 43
      candidate SNPs were associated with an increased risk of AVF failure. Whether
      other factors, like local hemodynamic circumstances, are more important or other
      SNPs play a role in AVF failure remains to be elucidated.

PMID- 23559681
TI  - Sensitivity to number: Reply to Gebuis and Gevers.
AB  - Past research showing a bias towards the larger non-symbolic number by adults and
      children in line bisection tasks (de Hevia & Spelke, 2009) has been challenged by
      Gebuis and Gevers, suggesting that area subtended by the stimulus and not number
      is responsible for the biases. I review evidence supporting the idea that
      although sensitivity to number might be relatively affected by visual cues,
      number is a major, salient property of our environment. The influence of non
      numerical cues might be seen as the concurrent processing of dimensions that
      entail information of magnitude, without implying that number is constructed out
      of those dimensions.

PMID- 23559682
TI  - Developmental Patterns of Alcohol Use in Relation to Persistence and Desistance
      of Serious Violent Offending among African American and Caucasian Young Men.
AB  - This study examined the association of alcohol use with persistence and
      desistance of serious violent offending among African American and Caucasian
      young men from adolescence into emerging adulthood. Five violence groups were
      defined: nonviolent, late-onsetters, desisters, persisters, and one-time
      offenders. We examined alcohol use trajectories for these groups from ages 12
      through 24/25 using a four-piecewise linear growth model (ages 12-14, 14-18, 18
      21, and 21-24/25). The persisters and desisters reported the highest levels of
      drinking at age 13. From ages 14 through 18, however, the late-onsetters showed a
      higher rate of increase in drinking, compared to the persisters and desisters.
      Starting from age 18, the desisters' drinking trajectory started to resemble that
      of the nonviolent group, who showed the highest rate of increase in drinking
      during emerging adulthood. By age 24/25 the persisters could not be distinguished
      from the late-onsetters; but were lower than the nonviolent and one-timer groups
      in terms of their drinking. At age 24/25, the desisters were not significantly
      different from the other violence groups, although they appeared most similar to
      the nonviolent and one-timer groups. There was no evidence that the association
      between drinking and violence differed for African Americans and Caucasians. The
      findings suggest that yearly changes in alcohol use could provide important clues
      for preventing violent offending.

PMID- 23559683
TI  - The (In)Significance of Race and Discrimination among Latino Youth: The Case of
      Depressive Symptoms.
AB  - Despite the growing population of Latinos in the United States, there is little
      research that explores how discrimination affects the mental health of Latino
      youth along racial lines. In this paper we ask two closely related questions.
      First, do black Latino youth have higher or lower symptoms of depression than
      nonblack Latinos? Second, is the relationship between race and depression among
      Latino youth buffered by discrimination stress? Results from the Transitions
      Study show that black Latino youth have significantly higher symptoms of
      depression than nonblack Latinos. The relationship between race and depression
      depends on daily-but not on lifetime-experiences of discrimination. The combined
      effect of race and discrimination holds in the face of a wide range of measures
      of stress, including major lifetime events, recent life events, and chronic
      stressors. These findings encourage future research that considers the mental
      health effects of racial variation among Latinos.

PMID- 23559684
TI  - Ugi/Robinson-Gabriel reactions directed toward the synthesis of 2,4,5
      trisubstituted oxazoles.
AB  - This Letter discloses a novel concise synthesis of a series of 2,4,5
      trisubstituted oxazoles via a tandem Ugi/Robinson-Gabriel sequence. Herein, 2,4
      dimethoxybenzylamine 1 was used as an ammonia equivalent in combination with
      arylglyoxal 3 and supporting Ugi reagents, an isonitrile and carboxylic acid. As
      such the product of the acid treated Ugi intermediate is ideally configured to
      undergo a Robinson-Gabriel cyclodehydration reaction to yield the desired oxazole
      scaffold 5.

PMID- 23559685
TI  - Distortion Product Otoacoustic Emissions: A Tool for Hearing Assessment and
      Scientific Study.
AB  - Distortion product otoacoustic emissions (DPOAEs) reflect outer hnir cell
      integrity and cochlear function. When used appropriately in the audiology clinic,
      they are an effective diagnostic tool and can detect hearing loss with accuracy.
      DPOAEs are easily and rapidly recorded in newborns and children, and provide
      basic hearing screening information as well as detailed diagnostic information in
      cases of suspected hearing loss. In the past decade, solid guidelines hnve been
      established to select the most effective recording parameters, thereby optimizing
      the DPOAE's diagnostic potential. DPOAEs also provide hearing scientists with a
      frequency-specific and noninvasive probe of the cochlea and cochlear amplifier
      function. Sophisticated and complex DPOAE-based experimental paradigms hnve been
      developed and applied to address scientific questions about cochlear function in
      humans. One such paradigm, DPOAE ipsilateral suppression, has been used
      effectively in our laboratory to study the maturation of cochlear function in
      newborns. Because of its proven accuracy as a clinical tool for the detection of
      hearing loss and its extensive use as a scientific tool for cochlear exploration,
      DPOAEs are likely to enjoy continued popularity and application in both the
      audiology clinic and the hearing science laboratory.

PMID- 23559686
TI  - Do Men Vary More than Women in Personality? A Study in 51 Cultures.
AB  - Do men vary more than women in personality? Evolutionary, genetic, and cultural
      arguments suggest that hypothesis. In this study we tested it using 12,156
      college student raters from 51 cultures who described a person they knew well on
      the 3rd-person version of the Revised NEO Personality Inventory. In most
      cultures, male targets varied more than female targets, and ratings by female
      informants varied more than ratings by male informants, which may explain why
      higher variances for men are not found in self-reports. Variances were higher in
      more developed, and effects of target sex were stronger in more individualistic
      societies. It seems that individualistic cultures enable a less restricted
      expression of personality, resulting in larger variances and particularly so
      among men.

PMID- 23559687
TI  - The road not taken: Women's life paths and gender-linked personality traits.
AB  - Key studies have established an association between women's social roles and
      their midlife personalities. The current research expands our understanding by
      examining personality traits in midlife women who followed normative or non
      normative life paths. The normative/non-normative distinction was based on two
      kinds of social roles that college-educated women undertook until midlife: work
      and family. Gender-linked personality traits were compared between (1) women in
      high status professions and women in moderate status professions; (2) women
      without children and women with children; and (3) single mothers and married
      mothers. Composite measures of gender-linked traits, based on expert-identified Q
      sort items, were used. Each non-normative social role group exhibited a different
      pattern of gender-linked personality traits inconsistent with conventional female
      gender roles.

PMID- 23559688
TI  - If it's red, it's not Vap: how competition among words may benefit early word
      learning.
AB  - One of the most prominent issues in early cognitive and linguistic development
      concerns how children figure out meanings of words from hearing them in context,
      since in many contexts there are multiple words and multiple potential referents
      for those words. Recent findings concerning on-line sentence comprehension
      suggest that, within the conversational context, potential referents compete for
      mappings to words. Three experiments examined whether such competitive processes
      may play a role in young children's learning of novel adjectives in an artificial
      word learning task. According to a competitive process view, although young
      children often mismap adjectives to whole objects rather than the properties of
      objects, explicitly mentioned familiar words should strongly map to referents
      consistent with those words and thereby decrease the likelihood of novel words
      being mismapped to these referents. Experiments 1 and 2 examined the role of the
      mere mention of familiar words and the role of word order in two year olds'
      ability to map a novel adjective to a property. Experiment 3 examined these
      processes in three year olds. The results indicate that lexical competition plays
      a particularly strong role in helping two year olds map a novel object to a
      property, whereas syntactic information about form class may also be informative
      to older children. The results suggest how fundamental processes of lexical
      competition in on-line word comprehension may give young learners a way to
      leverage known words in learning new words.

PMID- 23559689
TI  - Is there an optimal nasal pressure for treating obstructive sleep apnea-and if
      so, what is it?

PMID- 23559690
TI  - Latent Stick-Breaking Processes.
AB  - We develop a model for stochastic processes with random marginal distributions.
      Our model relies on a stick-breaking construction for the marginal distribution
      of the process, and introduces dependence across locations by using a latent
      Gaussian copula model as the mechanism for selecting the atoms. The resulting
      latent stick-breaking process (LaSBP) induces a random partition of the index
      space, with points closer in space having a higher probability of being in the
      same cluster. We develop an efficient and straightforward Markov chain Monte
      Carlo (MCMC) algorithm for computation and discuss applications in financial
      econometrics and ecology. This article has supplementary material online.

PMID- 23559691
TI  - Experiences from Pagan Women: A Closer Look at Croning Rituals.
AB  - In this qualitative study I explore how Pagan women conceptualize aging, more
      specifically social aging, through the ritual process of being a Pagan and
      becoming a Crone. The central question of this research revolves around how older
      women who identify as Pagan experience, understand, and conceptualize their
      social aging and their role as aging women in American society. Semi-structured
      interviews were used to collect data and explore the meaning of aging for women
      identifying as Pagan. Major emergent themes within the data demonstrate that the
      croning ritual, a central aspect of Paganism, affirms these women in their
      process of aging. These women, through the ritual of croning, are able to
      understand their aging as celebration, maintain a positive sense of self while
      aging, and reclaim visibility as aging women. These women were able to embed
      their experiences of aging within a unique and specific cultural framework, a
      spiritual and foundational framework cultivating a spiritual connection with
      nature.

PMID- 23559692
TI  - The Martyrdom Effect: When Pain and Effort Increase Prosocial Contributions.
AB  - Most theories of motivation and behavior (and lay intuitions alike) consider pain
      and effort to be deterrents. In contrast to this widely held view, we provide
      evidence that the prospect of enduring pain and exerting effort for a prosocial
      cause can promote contributions to the cause. Specifically, we show that
      willingness to contribute to a charitable or collective cause increases when the
      contribution process is expected to be painful and effortful rather than easy and
      enjoyable. Across five experiments, we document this "martyrdom effect," show
      that the observed patterns defy standard economic and psychological accounts, and
      identify a mediator and moderator of the effect. Experiment 1 showed that people
      are willing to donate more to charity when they anticipate having to suffer to
      raise money. Experiment 2 extended these findings to a non-charity laboratory
      context that involved real money and actual pain. Experiment 3 demonstrated that
      the martyrdom effect is not the result of an attribute substitution strategy
      (whereby people use the amount of pain and effort involved in fundraising to
      determine donation worthiness). Experiment 4 showed that perceptions of
      meaningfulness partially mediate the martyrdom effect. Finally, Experiment 5
      demonstrated that the nature of the prosocial cause moderates the martyrdom
      effect: the effect is strongest for causes associated with human suffering. We
      propose that anticipated pain and effort lead people to ascribe greater meaning
      to their contributions and to the experience of contributing, thereby motivating
      higher prosocial contributions. We conclude by considering some implications of
      this puzzling phenomenon. Copyright (c) 2011 John Wiley & Sons, Ltd.

PMID- 23559693
TI  - Low voltage picoliter droplet manipulation utilizing electrowetting-on-dielectric
      platforms.
AB  - Picoliter droplets actuated on an electrowetting-on-dielectric (EWD) actuator are
      demonstrated. In this study, the physical scaling of electrodes for 33 MUm and 21
      MUm EWD devices resulted in droplets of 12 pl and 5 pl being dispensed
      respectively in conjunction with 3 MUm SU8 gaskets. The stacked multi-layer
      insulators in the actuators consisted of 200 nm tantalum pentoxide (Ta2O5) and
      200 nm parylene C films deposited and coated with 70 nm of CYTOP. The voltages
      for dispensing droplets on chips without any external pressure sources are 17.1
      Vrms and 22 Vrms for these two sets of devices. A 12 pl droplet can be split into
      two 6 pl daughter droplets at 18.7 Vrms with 33 MUm electrode devices. Droplet
      manipulation is also demonstrated with paramagnetic beads and buffer solutions
      with proteins. In addition, electrodes with interlocking protrusions and special
      featured reservoir gasket are designed to facilitate droplet dispensing on these
      scaled EWD devices. In order to improve sealing of the two-piece sandwich EWD
      structure, a soft material, Norland Optical Adhesive (NOA), was coated on the top
      plate along with pressure on top. We demonstrate that based on fundamental
      theories and experiments, the dimensional scaling of EWD devices has not yet met
      a limitation as long as the EWD device can be sealed well.

PMID- 23559694
TI  - Hard evidence on soft skills.
AB  - This paper summarizes recent evidence on what achievement tests measure; how
      achievement tests relate to other measures of "cognitive ability" like IQ and
      grades; the important skills that achievement tests miss or mismeasure, and how
      much these skills matter in life. Achievement tests miss, or perhaps more
      accurately, do not adequately capture, soft skills-personality traits, goals,
      motivations, and preferences that are valued in the labor market, in school, and
      in many other domains. The larger message of this paper is that soft skills
      predict success in life, that they causally produce that success, and that
      programs that enhance soft skills have an important place in an effective
      portfolio of public policies.

PMID- 23559695
TI  - Open Access Ensures Effective Information Retrieval of Medical Literature in e
      Databases.

PMID- 23559696
TI  - "Air pollution in Delhi: Its Magnitude and Effects on Health".
AB  - Air pollution is responsible for many health problems in the urban areas. Of
      late, the air pollution status in Delhi has undergone many changes in terms of
      the levels of pollutants and the control measures taken to reduce them. This
      paper provides an evidence-based insight into the status of air pollution in
      Delhi and its effects on health and control measures instituted. The urban air
      database released by the World Health Organization in September 2011 reported
      that Delhi has exceeded the maximum PM10 limit by almost 10-times at 198 MUg/m3.
      Vehicular emissions and industrial activities were found to be associated with
      indoor as well as outdoor air pollution in Delhi. Studies on air pollution and
      mortality from Delhi found that all-natural-cause mortality and morbidity
      increased with increased air pollution. Delhi has taken several steps to reduce
      the level of air pollution in the city during the last 10 years. However, more
      still needs to be done to further reduce the levels of air pollution.

PMID- 23559697
TI  - Missing midwifery: relevance for contemporary challenges in maternal health.
AB  - Midwifery is rooted in public health, and most of its history has been community
      oriented. In India, midwifery evolved during the British rule; but over the years
      with changes in political and program priorities, the role and the capacity of
      midwives has changed substantially. The verticalization of national health
      programs has obscured the midwives' community focus and inhibited its
      contribution to the wider public health. There is a global acceptance and
      recognition of the midwifery model of care and skilled delivery for ensuring
      effective maternal health outcomes. The approaches are in line with local needs
      and have proved its effectiveness in resource-constrained settings. It is
      important to recognize the substantial contribution they make to public health,
      working to promote the long-term well-being of women, their babies and families,
      by offering information and advice on nutrition, supplementation, breastfeeding,
      and immunization. There is considerable scope for developing the midwifery model
      through enhancing the extent of their involvement in assessing health needs of
      local populations, designing, managing and evaluating maternal and health
      services, making timely and effective referrals and developing family-centered
      care.

PMID- 23559698
TI  - Equipment errors: a prevalent cause for fallacy in blood pressure recording - a
      point prevalence estimate from an Indian health university.
AB  - BACKGROUND: Blood pressure (BP) recording is the most commonly measured clinical
      parameter. Standing mercury sphygmomanometer is the most widely used equipment to
      record this. However, recording by sphygmomanometer is subject to observer and
      instrumental error. The different sources of equipment error are faulty manometer
      tube calibration, baseline deviations and improper arm bladder cuff dimensions.
      This is further compounded by a high prevalence of arm bladder miss-cuffing in
      the target population. OBJECTIVES: The study was designed to assess the presence
      of equipment malcalibrations, cuff miss-matching and their effect on BP
      recording. MATERIALS AND METHODS: A cross-sectional check of all operational
      sphygmomanometers in a health university was carried out for the length of the
      manometer tube, deviation of resting mercury column from "0" level, the width and
      length of arm bladder cuff and extent of bladder cuff-mismatch with respect to
      outpatient attending population. RESULTS: From the total of 50 apparatus
      selected, 39 (78%) were from hospital setups and 11 (22%) from pre-clinical
      departments. A manometer height deficit of 13 mm was recorded in 36 (92.23%) of
      the equipment in hospital and 11 (100%) from pre-clinical departments.
      Instruments from both settings showed significant deviation from recommended
      dimensions in cuff bladder length, width and length to width ratio (P < 0.001).
      Significant number of apparatus from hospital setups showed presence of mercury
      manometer baseline deviation either below or above 0 mmHg at the resting state
      (chi(2) = 5.61, D. F. = 1, P = 0.02). Positive corelationship was observed
      between manometer height deficit, baseline deviation and width of arm cuff
      bladder (Pearson correlation, P < 0.05). Bladder cuff mismatching in response to
      the target population was found at 48.52% for males and 36.76% for females. The
      cumulative effect of these factors can lead to an error in the range of 10-12
      mmHg. CONCLUSION: Faulty equipments and prevalent arm bladder cuff-mismatching
      can be important barriers to accurate BP measurement.

PMID- 23559699
TI  - Validity and Reliability of MOS Short Form Health Survey (SF-36) for Use in
      India.
AB  - BACKGROUND: Health is defined as the state of complete physical, mental and
      social well-being than just the absence of disease or infirmity. In order to
      measure health in the community, a reliable and validated instrument is required.
      OBJECTIVES: To adapt and translate the Medical Outcomes Study Short-Form Health
      Survey (SF-36) for use in India, to study its validity and reliability and to
      explore its higher order factor structure. MATERIALS AND METHODS: Face-to-face
      interviews were conducted in 184 adult subjects by two trained interviewers.
      Statistical analyses for establishing item-level validity, scale-level validity
      and reliability and tests of known group comparison were performed. The higher
      order factor structure was investigated using principal component analysis with
      varimax rotation. RESULTS: The questionnaire was well understood by the
      respondents. Item-level validity was established using tests of item internal
      consistency, equality of item-scale correlations and item-discriminant validity.
      Tests of scale-level validity and reliability performed well as all the scales
      met the required internal consistency criteria. Tests of known group comparison
      discriminated well across groups differing in socio-demographic and clinical
      variables. The higher order factor structure was found to comprise of two
      factors, with factor loadings being similar to those observed in other Asian
      countries. CONCLUSION: The item-and scale-level statistical analyses supported
      the validity and reliability of SF-36 for use in India.

PMID- 23559700
TI  - Attracting doctors to rural areas: a case study of the post-graduate seat
      reservation scheme in andhra pradesh.
AB  - BACKGROUND: Attracting doctors to rural posts is an ongoing challenge for health
      departments across different states in India. One strategy adopted by several
      states to make rural service attractive for medical graduates is to reserve post
      graduate (PG) seats in medical colleges for doctors serving in the public sector.
      OBJECTIVE: This study examines the PG reservation scheme in Andhra Pradesh to
      understand its role in improving rural recruitment of doctors and specialists,
      the challenges faced by the scheme and how it can be strengthened. MATERIALS AND
      METHODS: Qualitative case study methodology was adopted in which a variety of
      stakeholders such as government officials, health systems managers and serving
      Medical Officers were interviewed. This was supplemented with quantitative data
      on the scheme obtained from the Health, Medical and Family Welfare Department in
      Andhra Pradesh. RESULTS: The PG reservation scheme appears to have been one of
      the factors responsible in attracting doctors to the public sector and to rural
      posts, with a reduction in vacancies at both the Primary Health Centre and
      Community Health Centre levels. Expectedly, in-service candidates have a better
      chance of getting a PG seat than general candidates. However, problems such as
      the mismatch of the demand and supply of certain types of specialist doctors,
      poor academic performance of in-service candidates as well as quality of services
      and enforcement of the post-PG bond need to be resolved. CONCLUSION: The PG
      reservation scheme is a powerful incentive to attract doctors to rural areas.
      However, better monitoring of service quality, strategically aligning PG training
      through the scheme with the demand for specialists as well as stricter
      enforcement of the financial bond are required to improve the scheme's
      effectiveness.

PMID- 23559702
TI  - Influence of socioeconomic status on in-hospital mortality and morbidity after
      stroke in India: retrospective hospital-based cohort study.
AB  - OBJECTIVES: To determine an association between socioeconomic status and in
      hospital outcome in Indian patients with stroke. MATERIALS AND METHODS:
      Retrospective hospital-based cohort study. The hospital stroke register was used
      for this study. The independent variables were demographic job status, education,
      cardiovascular risk factors, comorbidities and the score on the Glasgow Coma
      Scale (GCS). The outcome variables were mortality and Barthel's index (BI) score
      at discharge. RESULTS: Data of 599 consecutive patients comprising 370 men
      (54.3%) and 229 women (33.6%) was available for analysis. Their mean age was
      55.63+/-15.36 years. Age, diagnosis (ischemic or hemorrhagic), midline shift,
      smoking and GCS were significantly associated with mortality and BI score
      (P<0.05). There was a statistically significant association between employment
      status and BI at discharge (P=0.03) in univariate analysis. In multivariate
      analysis, joblessness was associated with lower BI at discharge (P=0.02) after
      adjustment for GCS motor score and stroke subtype. CONCLUSION: Our study shows
      that in patients with stroke, lower employment status is associated with poor
      outcome at discharge from the hospital. The association is independent of other
      prognostic factors.

PMID- 23559701
TI  - Metabolic syndrome in the rural population of wardha, central India: an
      exploratory factor analysis.
AB  - BACKGROUND AND OBJECTIVES: Metabolic syndrome - a plausible precondition for type
      II diabetes and cardiovascular diseases is also on rise. To understand the
      mechanistic complexity of metabolic syndrome it is imperative to study the
      specific contribution of the determinants of metabolic syndrome. Such study can
      help to identify the most significant factor which may be of use in early
      detection as well as prevention efforts. Such information is scarcely available
      from India and especially from rural India. Hence, the present study was
      undertaken to explore for such factor which might be considered crucial for
      development of such pathogenesis particularly in rural population of Wardha.
      METHODS: A cross-sectional study comprising of 300 subjects was carried out in
      rural area of Primary Health Center, attached to medical college with approximate
      31,000 populations. The anthropometric parameters such as height, weight, waist
      circumference were measured. Overnight fasting samples were collected for lipid
      profile (total cholesterol, triglyceride, high density lipoproteins, low density
      lipoproteins, very low density lipoproteins) and fasting blood glucose levels.
      The National Cholesterol Education Programme Adult Treatment Panel, ATP-III
      guidelines were used to categorize the study subjects. As many of the variables
      are highly intercorrelated, exploratory factor analysis was carried out to reduce
      the data to a smaller number of independent factors that accounts for the most of
      the variances in the data. Principal component analysis was used as a method of
      extraction. RESULTS: For both sexes, three factors were extracted accounting for
      about 71% variance in the measured variables. An adiposity factor which accounted
      for highest explained variance (28%), was the initial factor extracted. It was
      loaded positively by waist circumference, triglyceride, and very low density
      lipoprotein and negatively loaded by high density lipoprotein. Second factor
      extracted was a cholesterol factor which explained about 20% variance. It was
      positively loaded by total cholesterol and low density lipoprotein. Blood
      pressure factor was third to be extracted which again explained about 20%
      variance. It was positively loaded by systolic and diastolic blood pressure.
      INTERPRETATION AND CONCLUSION: The results clearly indicate the significance of
      visceral adiposity over the obesity in general or simple abdominal obesity
      measured anthropometrically as a pathogenic determinant of the metabolic
      syndrome. The most consistent factor has been found to be dyslipidemia which
      explained major share of the observed variance and the most significant load of
      this factor being rested on triglyceride and the VLDL level. Hence, we conclude
      measurement of triglyceride might be a rewarding screening parameter for
      assessment of cardio-metabolic risk in general populace and warrants a large
      scale study focusing into this issue.

PMID- 23559703
TI  - Effect of Community-based Behavior Change Communication on Delivery and Newborn
      Health Care Practices in a Resettlement Colony of Delhi.
AB  - BACKGROUND: Neonatal morbidity and mortality in India continue to be high. Among
      other reasons, newborn care practices are major contributors for such high rates.
      OBJECTIVE: To assess the effect of behavior change communication (BCC) package
      among pregnant women regarding neonatal care. MATERIALS AND METHODS:
      Semistructured and pretested schedule was used to interview 200 multigravidas on
      various aspects of neonatal care. Based on the preliminary data, BCC package was
      designed and implemented in intervention block in the community. Follow-up was
      done to find out change in their behavior. STATISTICAL ANALYSIS: Data were
      analyzed using Epi info and Fischer exact test and chi-square test were applied
      in the baseline data. A P value of less than 0.05 was considered significant.
      Effect of the BCC package is given in terms of relative risk. RESULTS: BCC
      package increased 1.76 times higher number of deliveries conducted by trained
      dais in intervention group. There was significant improvement in using sterile
      cord tie (P = 0.01), applied nothing to the cord (P < 0.0001) and giving bath to
      their baby within 6 h of birth (P = 0.02) in intervention group as compared to
      nonintervention group. Significant difference was found between the two groups
      with regard to breastfeeding practices of baby. Harmful practices were reduced in
      the intervention group. Significant improvement was found in intervention group
      as compared to nonintervention group with regard to knowledge of danger signals,
      physiological variants, management of breastfeeding-related problems, and
      awareness of skin-to-skin technique for the management of hypothermic baby.
      CONCLUSION: Inadequate knowledge and adverse practices regarding neonatal care
      among mothers in study areas were found. BCC package had favorable impact on
      behavior of mothers for neonatal care in intervention group.

PMID- 23559704
TI  - Mortality trend and pattern in tertiary care hospital of solapur in maharashtra.

PMID- 23559705
TI  - Prevalence of Anemia and Role of beta(E)-Globin Gene as an Associating Factor
      Among College Students of Assam: A Preliminary Report.

PMID- 23559706
TI  - R-software: A Newer Tool in Epidemiological Data Analysis.

PMID- 23559707
TI  - "All is Not Well" with Medical Tourism.

PMID- 23559708
TI  - Self-reported Chronic Diseases and Occupational Health Risks Among Bank Employees
      of Southern Karnataka City, India.

PMID- 23559709
TI  - Tc-99m glucoheptonate is poor man's fluorodeoxyglucose.
AB  - While fluoro-deoxy-glucose (FDG) has emerged as an important radiotracer for
      imaging tumors, myocardial viability and infection, the role of other glucose
      analogues should also be explored. Tc-99m Glucoheptonate (GHA) has been used for
      imaging brain tumors and lung tumors. The uptake mechanism may be linked to GLUT
      1 (Glucose transporter) and GLUT-4 expression similar to FDG. GHA is easily
      available and cheap. With the availability of single photon emission computed
      tomography/computed tomography (SPECT/CT), GHA imaging should be re-explored as a
      tumor agent and also for imaging myocardial viability.

PMID- 23559710
TI  - Role of (18)F-fluorodeoxyglucose Positron Emission Tomography scan in
      differentiating enhancing brain tumors.
AB  - AIM: To determine whether F-18-fluorodeoxyglucose positron emission tomography (F
      18-FDG PET) can be used to differentiate among common enhancing brain tumors such
      as gliomas, metastatic brain tumors, and lymphoma. MATERIALS AND METHODS: We
      evaluated 20 patients with an enhancing brain tumor on magnetic resonance imaging
      (MRI). FDG PET scan was done in all patients pre operatively. For PET image
      analysis, regions of interest were placed over the tumor (T), contralateral
      cortex (C), and white matter (WM). Average and maximum pixel values were
      determined at each site. On the basis of these measurements, average and maximum
      standard uptake values (SUV avg and SUV max ) were calculated, and comparisons
      among lesions were then made. RESULTS: SUVavg and SUVmax are significantly higher
      for central nervous system (CNS) lymphoma than for other tumors (P < 0.01). High
      grade gliomas showed significantly higher SUVavg and SUVmax than the low grade
      gliomas (P < 0.05) and metastatic tumor showed higher SUVavg and SUVmax than all
      gliomas, both low and high grade (P < 0.05). When the lowest values of CNS
      lymphoma parameter were used as cutoff levels to distinguish CNS lymphomas from
      other tumors (i.e. 100% sensitivity), SUVmax was the most accurate parameter.
      Using a SUVmax of 15.0 as a cutoff for diagnosing CNS lymphoma, only one case of
      metastasis (SUV max , 16.3) was found to be false positive in this study.
      CONCLUSION: FDG PET appears to provide additional information for differentiating
      common enhancing malignant brain tumors, namely lymphoma versus high grade glioma
      and metastatic tumor, particularly when differential diagnoses are difficult to
      narrow using MRI alone.

PMID- 23559711
TI  - Fluorodeoxyglucose positron emission tomography-computed tomography in evaluation
      of pelvic and para-aortic nodal involvement in early stage and operable cervical
      cancer: Comparison with surgicopathological findings.
AB  - INTRODUCTION: Nodal metastases in cervical cancer have prognostic implications.
      Imaging is used as an adjunct to clinical staging for evaluation of nodal
      metastases. Fluorodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) has an advantage of superior resolution of its CT component
      and detecting nodal disease based on increased glycolytic activity rather than
      node size. But there are limited studies describing its limitations in early
      stage cervical cancers. OBJECTIVE: We have done meta-analysis with an objective
      to evaluate the efficacy of FDG PET/CT and its current clinical role in early
      stage and operable cervical cancer. MATERIALS AND METHODS: Studies in which FDG
      PET/CT was performed before surgery in patients with early stage cervical cancers
      were included for analysis. PET findings were confirmed with histopathological
      diagnosis rather than clinical follow-up. FDG PET/CT showed lower sensitivity and
      clinically unacceptable negative predictive value in detecting nodal metastases
      in early stage cervical cancer and therefore, can not replace surgicopathological
      staging. False negative results in presence of microscopic disease and sub
      centimeter diseased nodes are still the area of concern for metabolic imaging.
      However, these studies are single institutional and performed in a small group of
      patients. There is enough available evidence of clinical utility of FDG PET/CT in
      locally advanced cervical cancer. But these results can not be extrapolated for
      early stage disease. CONCLUSION: The current data suggest that FDG PET/CT is
      suboptimal in nodal staging in early stage cervical cancer.

PMID- 23559712
TI  - Incremental benefit of SPECT + CT bone scans over conventional planar and SPECT
      bone scans in vertebroplasty.
AB  - STUDY DESIGN: Planar bone scans with SPECT and SPECT + CT were performed in those
      patients who underwent peri-operative evaluation for vertebroplasty. The scans
      were evaluated separately to identify the "culprit" vertebra (e) by two readers
      and their results were analyzed. OBJECTIVE: Use of planar and SPECT bone scan for
      identifying the "culprit" vertebra (e) for vertebroplasty is well established.
      SPECT + CT is a relatively recent imaging tool providing co-registered fused
      images. Theoretical advantages of SPECT + CT over conventional SPECT imaging
      needs to be evaluated and documented. SUMMARY OF BACKGROUND DATA: Percutaneous
      stabilization of collapsed vertebra by bone cement has now become a standard
      procedure. However, it is essential to localize the correct vertebra. Imaging
      modalities like CT scan provides structural or anatomical information where as
      bone scan (planar + SPECT images) provides more functional or physiological
      information. Combination of these two imaging modalities is expected to provide
      much more than information obtained by any one imaging modality separately. To
      the best our knowledge, there is no reference available in the literature
      adopting this approach. MATERIALS AND METHODS: Two expert readers, blinded to
      patient history, evaluated the scans. They independently analyzed planar + SPECT
      only images followed by SPECT/CT fused images with the aim to identify the
      acutely fractured vertebra for vertebroplasty. RESULTS: Interpretations changed,
      on average, 50% of the time as a result of the additional information provided by
      SPECT + CT. SPECT + CT more precisely localizes tracer abnormalities in the
      vertebra compared to SPECT imaging alone. CONCLUSION: The greatest value of co
      registered SPECT + CT bone scan lies in the accurate localization of affected
      vertebrae in complicated cases of multiple collapsed vertebrae of different ages
      as well as in the post-vertebroplasty setting.

PMID- 23559713
TI  - Poor Tc-99m dimercaptosuccinic acid uptake, re-evaluation with Tc-99m MAG3
      scintigraphy in Lowe syndrome.
AB  - Tc-99m dimercaptosuccinic acid (DMSA) is filtered through the glomeruli and
      reabsorbed by the proximal tubules as low molecular weight proteins. In Lowe
      syndrome this mechanism is impaired and so poor DMSA uptake is seen. Poor DMSA
      uptake was shown in very few studies, but none mentioned normal Tc-99m MAG3
      uptake. In this case, the patient had poor DMSA uptake, normal MAG3 uptake and a
      neurogenic bladder in anterior to the left kidney that attenuates left kidney.

PMID- 23559714
TI  - Oncogenic osteomalacia diagnosed by blood pool scintigraphy.
AB  - Oncogenic osteomalacia is a rare metabolic bone disease characterized by
      phosphaturia and hypophosphatemia. Certain tumors secrete a phosphaturic factor,
      which results in this metabolic abnormality; this factor called as phosphatonin,
      is in fact a fibroblast growth factor 23 (FGF-23) involved closely in phosphate
      homeostasis and skeletogenesis. Complete excision of these tumors facilitates
      reversal of the problem. We have reported here the case of a patient who was
      crippled with this disease and on thorough investigation revealed an oncogenic
      osteomalacia with tumor focus in the right tibia. The tumor was identified as a
      mesenchymal tumor, i.e., hemangiopericytoma. Tumor excision alleviated patient
      symptoms with rapid symptomatic and biochemical improvement.

PMID- 23559715
TI  - New axillary lymph nodal F-18 fluoro-deoxy glucose uptake in an interim positron
      emission tomography scan - not always a sign of disease progression.
AB  - Fluoro-deoxy glucose (FDG) is a non-specific tracer and may accumulate in non
      malignant conditions causing potential pitfalls leading to false-positive
      interpretations of interim positron emission tomography scan. We report a case of
      a potential pitfall of false-positive axillary lymph nodal F-18 FDG uptake caused
      by injection extravasation.

PMID- 23559716
TI  - Triple ectopic thyroid: A rare entity.
AB  - Ectopic thyroid tissue is an uncommon congenital aberration. It is extremely rare
      to have three ectopic foci at three different sites. The thyroid scan has been
      used successfully to diagnose ectopic thyroid tissue. We report a case of ectopic
      thyroid tissue at base of tongue, another at the level of hyoid and third one as
      aberrant tissue at suprahyoid location in a 16 year old female who presented with
      swelling in front of neck. This patient was clinically diagnosed as thyroglossal
      cyst and was being planned for surgery. Preoperative thyroid scan helped in
      establishing diagnosis of ectopic thyroid which was the only functioning thyroid
      tissue. Thus, it prevented unnecessary surgery. Therefore it is suggested that
      thyroid scan and USG/CT scan must be done as routine work up in neck swellings
      pre operatively to avoid unnecessary surgeries.

PMID- 23559717
TI  - Solid variant of papillary carcinoma thyroid in a child with no history of
      radiation exposure.
AB  - Solid variant is a rare and poorly characterized variant of papillary thyroid
      carcinoma (PTC) and comprises approximately 3% of PTCs. It is more common in
      children and has high propensity for extrathyroidal metastasis. It is seen in
      higher proportion in post-radiation PTCs and has been seen in more than one-third
      of post Chernobyl radiation induced PTCs in some studies. It usually presents
      with differential diagnosis of poorly differentiated carcinoma versus anaplastic
      versus medullary thyroid carcinoma versus metastasis from extrathyroidal
      malignancy on fine needle aspiration cytology. This report describes a case of
      solid variant of PTC in a child who had no history of radiation exposure and
      shows the importance to be given to histopathology when the pre-operative
      diagnosis is not clear.

PMID- 23559718
TI  - Bilateral axillary lymph node uptake of radiotracer during lower extremity and
      scrotal lymphoscintigraphy in a case of primary scrotal lymphoedema.
AB  - Lymphoscintigraphy is a useful technique for the evaluation of lymphatic function
      in the presence of limb swelling. The authors report a case where genital
      swelling in a 20-year-old man was investigated by lymphoscintigraphy. We
      performed lower limb lymphoscintigraphy and scrotal lymphoscintigraphy in the
      patient on two different days. Lower limb revealed dermal backflow pattern in
      lower limbs, inguinoscrotal reflux of the lymph and unexpected avid radiotracer
      uptake in the axillae bilaterally. Scrotal lymphoscintigraphy revealed slow
      movement of the lymph from the scrotal skin and again unexpected avid radiotracer
      uptake in the axillae bilaterally. Findings were concluded as congenital
      hypoplasia of lymphatics in lower limbs, congenital lymphectasia/compensatory
      megalymphatics in scrotum and aberrant lymphatic pathway, possibly due to
      malfunctioning/nonfunctioning thoracic duct.

PMID- 23559719
TI  - Febrile renal transplant recipient with discordant findings of (99m)Tc-Leukoscan
      (Sulesomab) and (67)Ga-citrate scan in pyelonephritis.
AB  - Nuclear medicine techniques like (99m)Tc-Leukoscan and (67)Ga-citrate scan have
      been used in localizing infectious pathologies in renal transplant patients. We
      present an interesting case of febrile renal transplant with discordant findings
      of tracer uptake in the transplant kidney on (99m)Tc-Leukoscan and (67)Ga-citrate
      scan.

PMID- 23559720
TI  - Bilateral axillary and internal mammary drainage in breast cancer without prior
      surgery during sentinel node mapping.
AB  - Lymphatic drainage outside the ipsilateral axilla in breast cancer is discovered
      in as many as 25% of all sentinel lymph node procedures and it is evidenced by
      lymphoscintigraphy. Contralateral axillary drainage is a rare clinical situation,
      mostly if there is not prior breast surgery, but this situation is extremely
      exceptional if we also found internal mammary chain drainage. We have not found
      such a case published in literature. This atypical finding is source of doubts
      because it could have clinical implications in the management of patients. We
      present a woman just diagnosed of breast carcinoma with hot nodes in bilateral
      axillary and ipsilateral internal mammary chain lymph nodes, shown by
      preoperative lymphoscintigraphy. We review published cases with contralateral
      axillary drainage, which enhance the role of scintigraphic procedure in such
      cases and show induced controversies in selecting the most adequate management.

PMID- 23559721
TI  - False positive localisation of C-11 methionine in a colloid nodule.
AB  - A 45-year-old female diagnosed with carcinoma of the left breast on
      histopathological examination underwent both (18)F-flourodeoxyglucose (FDG) and
      11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) as
      part of a protocol comparing the utility of these tracers for predicting a
      response to neoadjuvant chemotherapy in breast carcinoma. Abnormal FDG and MET
      accumulation was noted in the left breast primary, left axillary lymph nodes, and
      also in a well-defined nodule present in the left lobe of the thyroid gland.
      Keeping in mind the possibility of thyroid neoplasm/metastasis, the patient was
      referred for fine needle aspiration cytology (FNAC) from the thyroid nodule that
      revealed features of a simple colloid nodule. Focal thyroid lesions incidentally
      found on (18)F-FDG PET/CT have a high risk of thyroid malignancy. Non-specific
      accumulation of FDG in thyroid adenomas is also known. This case highlights a
      potential cause for false positive on C-11 MET PET/CT in colloid adenomas, which
      should be kept in mind while using this tracer for oncological indications.

PMID- 23559722
TI  - Importance of diffuse versus focal F-18 fluoro-deoxy-glucose uptake in
      oesophagus.

PMID- 23559723
TI  - Response to "Does thyroxine suppression therapy help to rationalize surgery in
      benign euthyroid nodules".

PMID- 23559724
TI  - Clinical profile, species-specific severity grading, and outcome determinants of
      snake envenomation: An Indian tertiary care hospital-based prospective study.
AB  - OBJECTIVE: We undertook this study to assess the clinical profile and outcome
      determinants of different snake envenomation as well as to assign species
      specific severity grade to different cases based on clinico - laboratory evidence
      scale. MATERIALS AND METHODS: A prospective clinico - epidemiologic evaluation
      for outcome determinants of snakebite envenomation was carried out based on a
      clinico - laboratory severity grading scale, among 76 patients over a period of 2
      years, in a tertiary care hospital in southern India. RESULTS: Majority of
      patients were male agricultural workers (53.9%) followed by housewives (19.7%),
      and students (9.2%). Occurrence of viper snake envenomation with hemotoxic
      syndrome (73.68%) was highest followed by cobra and krait envenomation with
      neurotoxic (19.73%) and hemo - neurotoxic (5.3%) syndrome, respectively. On the
      contrary, maximum mortality and severity was seen in krait (60%) followed by
      cobra (13.33%) and viper (8.9%) envenomation. The average dose of anti-snake
      venom (ASV) administered varied from 9.83 (+/-7.22) to 20.25 (+/-4.92) vials
      throughout grade I to IV in all snake species envenomation. An increase in
      severity grade, ASV dose, and mortality were observed with the corresponding
      delay in 'bite to needle time.' Also, initial traditional treatments and krait
      species envenomation were significantly associated with higher grades of severity
      and mortality. CONCLUSION: There is an urgent need to spread awareness among the
      community for avoidance of traditional treatment and any delay in medical
      intervention in snakebite incidents.

PMID- 23559726
TI  - Severe hemophagocytic lymphohistiocytosis in adults-experience from an intensive
      care unit from North India.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) has been reported to
      complicate fulminant tropical infections but data on severe HLH with multi-organ
      dysfunction (MODS) are scant. MATERIALS AND METHODS: Retrospective review of
      medical electronic records of our intensive care unit (ICU) over a 2-year period.
      RESULTS: We describe 10 adult patients with HLH and MODS. Patients had short
      symptom duration prior to presentation and had rapid deterioration during their
      hospitalization course. Fever, organomegaly, neurologic abnormalities, hepatic
      abnormalities, and cutaneous signs were very common. No patient had diagnosed HLH
      at ICU admission (median 4 criteria [Inter Quartile Range 2-4.25]). All patients
      required mechanical ventilation and 80% required vasopressors. Infection
      associated HLH (IAHS) was the most common etiology (80%). Seventy percent (7/10)
      of patients were treated with steroids and 20% received intravenous
      immunoglobulin. Etoposide and/or cyclosporine were administered in 20% (2/10).
      Nosocomial infections occurred in 40% and the ICU mortality was 70%. CONCLUSIONS:
      Severe HLH with MODS has a very high mortality. Data on adult cohorts with IAHS
      in the tropics with defined treatment protocols are urgently needed.

PMID- 23559725
TI  - Point of care serum lactate levels as a prognostic marker of outcome in complex
      pediatric cardiac surgery patients: Can we utilize it?
AB  - BACKGROUND: Post-operative course after complex pediatric cardiac surgery is
      unpredictable. Although, change in arterial lactate levels has been used as a
      surrogate marker for many years, scientific evidence correlating the early
      perioperative lactate levels with outcome is still lacking. OBJECTIVE: To
      evaluate the trends in lactate levels from intraoperative period to an extended
      post-operative period in pediatric intensive care unit (PICU) and to assess its
      usefulness as a prognostic marker. DESIGN: Prospective observational study.
      SETTING: Tertiary pediatric cardiac surgical unit. PATIENTS: Thirty-five non
      consecutive children aged 1-140 months who underwent surgery for congenital heart
      diseases (CHD) on cardiopulmonary bypass (CPB). INTERVENTION: None. MATERIALS AND
      METHODS: ARTERIAL BLOOD LACTATE LEVELS WERE OBTAINED AT THE FOLLOWING TIME
      POINTS: After induction of anesthesia, 15 and 45 min after institution of CPB, at
      the start of rewarming, after sternotomy closure, then at 1, 6, 24, and 48 h in
      PICU. Other hemodynamic and clinical variables, CPB variables, blood gas values,
      and laboratory variables were also recorded. RESULTS: Four patients died out of
      35 patients (11.4%). Non-survivors showed significant persistent elevation in
      lactates (>4.0 mmol/l). Peak lactates correlate significantly with longer aortic
      cross clamp time, CPB duration, ventilation hours and PICU stay. CONCLUSION:
      Early point of care lactate can be a useful prognostic marker in post-cardiac
      surgery patients in adjunct with other parameters measured in PICU. This
      reiterates the importance of measuring lactates and timely recognition of at-risk
      patients, which on early intervention can help in reducing post-operative
      morbidity and mortality.

PMID- 23559727
TI  - The use of extracorporeal life support in adolescent amlodipine overdose.
AB  - Calcium channel blocker (CCB) toxicity is associated with refractory hypotension
      and can be fatal. A 13 year old young woman presented to the emergency
      department(ED) six hours after an intentional overdose of amlodipine,
      barbiturates, and alcohol. She remained extremely hypotensive despite the
      administration of normal saline and calcium chloride and despite infusions of
      norepinephrine, epinephrine, insulin, and dextrose. Due to increasing evidence of
      end organ dysfunction, Extracorporeal Life Support (ECLS) was initiated 9 hours
      after presentation to the ED. The patient's blood pressure and end organ function
      immediately improved after cannulation. She was successfully decannulated after
      57 hours of ECLS and was neurologically intact. Patients with calcium channel
      blocker overdose who are resistant to medical interventions may respond favorably
      to early ECLS.

PMID- 23559728
TI  - Living after sudden death: A case report of Naxos disease.
AB  - Naxos disease is a recessive inherited condition with arrhythmogenic right
      ventricular dysplasia (ARVD) and a peculiar cutaneous phenotype (woolly hair and
      a palmoplantar keratoderma). Woolly hair appears from birth, palmoplantar
      keratoderma develops during childhood and cardiomyopathy is clinically manifested
      by adolescence. Patients present with syncope, sustained ventricular tachycardia
      or sudden death. We report a case of a 14 year old boy from Spain, who was
      admitted into our emergency room after being resuscitated from cardiac arrest,
      secondary to malignant ventricular tachycardia that developed while he was
      playing basketball.

PMID- 23559729
TI  - Overcoming the problem of pseudohypoxemia in myeloproliferative disorders:
      Another trick in the bag.
AB  - Pseudohypoxaemia or spurious hypoxaemia is a recurrent problem faced on arterial
      blood gas analysis in patients with hyperleucocytosis leading to management
      dilemmas and unnecessary respiratory interventions. Various methods have been
      suggested to reduce the magnitude of this problem. We report a case of
      pseudohypoxaemia due to blast crisis in a patient of chronic myeloid leukaemia
      where arterial blood gas analysed from precooled syringe helped us resolve the
      problem and hastened our weaning from oxygen therapy.

PMID- 23559730
TI  - Cerebral venous thrombosis presenting as multiple lower cranial nerve palsies.
AB  - Cerebral venous thrombosis (CVT) is a well-recognized entity, but its clinical
      presentation is varied and often mimics many neurological disorders, making it a
      diagnostic challenge. Cerebral venous thrombosis has a wide spectrum of signs and
      symptoms, which may evolve suddenly or over weeks. It mimics many neurological
      conditions such as meningitis, encephalopathy, idiopathic intracranial
      hypertension, and stroke. Cerebral venous thrombosis presenting as multiple lower
      cranial nerve palsies, are rarely reported. We describe a pregnant lady who
      presented with sensorineural deafness of the right ear and paralysis of the
      9(th), 10(th), and 12(th) cranial nerves on the right side. She was diagnosed to
      have thrombosis of the right transverse sinus and sigmoid sinus with extension to
      the jugular vein and confluence of sinuses. She improved with anticoagulant
      treatment.

PMID- 23559731
TI  - Spontaneous subarachnoid hemorrhage as a differential diagnosis of pre-hospital
      cardiac arrest.
AB  - Spontaneous subarachnoid hemorrhage is the most common neurological disorder
      leading to pre-hospital cardiac arrest. ECG changes in SAH may mimic myocardial
      infarction or ischemia, and thus lead to delayed treatment of the primary
      problem. Early identification of SAH-induced cardiac arrest with the use of
      computed tomography scan of the brain obtained immediately after resuscitation
      will aid emergency physicians make further decisions. The overall prognosis of
      patients who are resuscitated is extremely poor. But, prompt neurosurgical
      referral and multidisciplinary intensive care management can improve the survival
      rate and the functional outcome. Thus, physicians should consider SAH as a
      differential diagnosis in patients presenting with pre-hospital cardiac arrest.

PMID- 23559732
TI  - Unusual presentation of pericardial effusion.
AB  - Cough syncope is classically described in patients with chronic obstructive
      pulmonary disease, and it is quite rare to find a treatable condition for the
      same. However, it is extremely rare to have cough syncope due to pericardial
      effusion. We present a case of pericardial effusion who presented to the
      intensive care with cough syncope.

PMID- 23559733
TI  - Chronic subdural hematoma in a child with acute myeloid leukemia after
      leukocytosis.
AB  - Severe complications that develop in the early stages in patients with acute
      leukemia have a mortal course. Bleeding, leukostasis, and less frequently,
      infections are responsible for early mortality. Hemorrhage is most common in
      acute leukemia and usually leads to death. Hemorrhage may occur due to
      chemotherapy or bone marrow transplantation in patients with acute leukemia.
      Leukocytosis, thrombocytopenia, sepsis, and coagulopathy increase the risk of
      bleeding. There may be multiple etiologic factors. Subdural or subarachnoid
      hemorrhage is less common than an intra-axial hemorrhage. The incidence of
      spontaneous subdural hematoma is higher in patients with leukemia. Although
      advances in the treatment of platelet transfusion and disseminated intravascular
      coagulation have decreased the incidence of hemorrhagic complications in patients
      receiving chemotherapy for acute leukemia, intracranial hemorrhage-related deaths
      are a significant problem. We discussed the etiology and management of chronic
      subdural hematoma detected in a two-year-old male patient with Acute Myeloid
      Leukemia and hyperleukocytosis.

PMID- 23559734
TI  - Acute methotrexate toxicity presenting as multiorgan failure and acute
      pneumonitis: A rare case report.
AB  - Acute methotrexate toxicity rarely presents as medical emergency in form of
      multiorgan failure. Acute pneumonitis following low-dose methotrexate is rarely
      reported in literature. It is important to recognize this, as the drug must be
      discontinued immediately and rescue measures in form of folinic acid and
      hydration instituted promptly.

PMID- 23559735
TI  - Perioperative management of a patient with myxedema coma and septicemic shock.
AB  - Myxedema coma is a life-threatening but uncommon complication of long-standing,
      neglected hypothyroidism. It was first reported by Ord in 1879. Till date only
      around 200 cases have been reported in literature. The incidence in European
      countries is 0.22 per million per year. No epidemiological data is available from
      the Indian subcontinent. We are reporting the case of an elderly lady who went
      into life-threatening myxedema coma along with septicemic shock, and was
      successfully treated with oral thyroxine.

PMID- 23559736
TI  - Severe suicidal digoxin toxicity managed with resin hemoperfusion: A case report.
AB  - Owing to its wide and easy availability, digoxin has got a significant abuse
      potential and may be used for suicidal purposes. Digoxin-specific antibody (Fab)
      fragments have become the mainstay of therapy for severe digoxin toxicity and
      have significantly helped in reducing mortality. However, due to its high cost
      and limited availability alternative measures may need to be used to manage
      severe intoxications especially in countries like India, where Fab fragments are
      unavailable. Here, we present a case of a young female who presented to our
      casualty with alleged history of consumption of 17.5 mg of digoxin tablets. After
      admission to ICU, she developed atrioventricular blocks with hemodynamic
      instability which had to be managed with temporary pacemaker. Her serum digoxin
      levels were high (12.63 ng/ml) and in the absence of Fab fragments, resin
      hemoperfusion was done which drastically reduced the serum digoxin levels and
      reverted the symptoms.

PMID- 23559737
TI  - A life-threatening case of disseminated nocardiosis due to Nocardia brasiliensis.
AB  - Nocardiosis is a rare disease caused by infection with Nocardia species, aerobic
      actinomycetes with a worldwide distribution. A rare life-threatening disseminated
      Nocardia brasiliensis infection is described in an elderly, immunocompromised
      patient. Microorganism was recovered from bronchial secretions and dermal
      lesions, and was identified using molecular assays. Prompt, timely diagnosis and
      appropriate treatment ensured a favorable outcome.

PMID- 23559738
TI  - Acute barium intoxication following ingestion of soap water solution.
AB  - We present a rare case in which a young girl ingested a solution of a hair
      removing soap. The ingestion resulted in profound hypokalemia and severe acidosis
      leading to flaccid paralysis, respiratory arrest and ventricular arrhythmias.
      Ultimately the patient made complete recovery. The soapwas found to contain
      barium sulfide. The degree of paralysis and acidosis appeared to be directly
      related to serum potassium levels.

PMID- 23559740
TI  - Issues about diagnosis and treatment of toxic epidermal necrolysis.

PMID- 23559739
TI  - Hyperlactatemia caused by intra-venous administration of glycerol: A case study.
AB  - Glyceol((r)) is an intracranial pressure reducing agent composed of 5% fructose
      and concentrated glycerol. Although rapid administration of fructose is known to
      cause lactic acidosis, little is known about hyperlactatemia caused by
      Glyceol((r)) administration itself in adults. We observed an adult case of
      hyperlactatemia occurred after administration of 200 mL of Glyceol((r)) over a
      period of 30 minutes. Since there was no evidence of an underlying liver disease
      or metabolic abnormality, and no findings of sepsis or impaired tissue perfusion,
      the cause of this condition was deemed to be the rapid loading of fructose
      contained as a constituent of Glyceol((r)). We then performed a retrospective
      chart review and found other 9 cases admitted to Jichi Medical University
      Hospital ICU and administered Glyceol((r)) during the past year. Their lactate
      levels increased in general, peaked approximately 45 minutes after Glyceol((r))
      administration and returned to pre-administration levels around 3 hours after.
      Although hyperlactatemia is an important indicator of sepsis and impaired tissue
      perfusion, caution is required when performing such an assessment in patients
      being administered Glyceol((r)).

PMID- 23559741
TI  - Authors' reply.

PMID- 23559742
TI  - Use of naloxone in valproate overdose.

PMID- 23559743
TI  - Upside-down twist with angulation maneuver for guide wire insertion in ultrasound
      guided supraclavicular approach for subclavian catheterization: Our experience.

PMID- 23559744
TI  - Aluminum phosphide poisoning and development of hemolysis and methemoglobinemia.

PMID- 23559745
TI  - Functional assignment to maize group 1 LEA protein EMB564 within the cell nucleus
      using computational analysis.
AB  - Maize protein EMB564 is a member of group 1 LEA (late embryogenesis abundant)
      proteins. Currently, the molecular functions of group 1 LEA proteins remain
      largely unclear. We here report on the functional assignment to EMB564 by
      computational analysis. EMB564 is predicted as nuclear localization by five
      different predictors including CELLO, Plant-mPLoc, WoLF PSORT, Predotar and
      TargetP. EMB564 is found to be remote homologous with DNA/RNA helicases and
      single-stranded DNA-binding proteins, and their sequences contains similar
      DNA/RNA binding sites. Furthermore, the three-dimensional (3D) model of EMB564
      structurally resembles a variety of nuclear and DNA/RNA-binding proteins,
      especially those involving in the regulation of cell division, chromosomal
      replication and DNA unwinding or repairing. Our results reveal that EMB564
      protein is most likely to function within the cell nucleus.

PMID- 23559746
TI  - Molecular characterization of alpha-amylase from Staphylococcus aureus.
AB  - Staphylococcus aureus is one of the prominent Gram positive human pathogen
      secretes many surface and secretary proteins including various enzymes and
      pathogenic factors that favour the successful colonization and infection of host
      tissue. alpha-amylase is one of the enzymes secreted by S. aureus which catalyses
      the breakdown of complex sugars to monosaccharides, which are required for
      colonization and survival of this pathogen in any anatomical locales. In the
      present study we have cloned, sequenced, expressed and characterized alpha
      amylase gene from S. aureus ATCC12600. The recombinant enzyme has a molecular
      weight of 58kDa and the kinetics showed Vmax 0.0208+/-0.033 (mg/ml)/mg/min and Km
      10.633+/-0.737mg/ml. The multiple sequence analysis showed alpha- amylase of S.
      aureus exhibited large differences with Bacillus subtilis and Streptococcus
      bovis. As the crystal structure of S. aureus alpha- amylase was unavailable, we
      used homology modelling method to build the structure. The built structure was
      validated by Ramachandran plot which showed 90% of the residues in the allowed
      region while no residue was found in the disallowed region and the built
      structure was close to the crystal structure with Z-Score: -6.85. The structural
      superimposition studies with alpha- amylases of Bacillus subtilis and
      Streptococcus bovis showed distinct differences with RMSD values of 18.158Aand
      7.091A respectively which correlated with enzyme kinetics, indicating alpha
      amylase is different among these bacteria.

PMID- 23559747
TI  - High-throughput virtual screening and docking studies of matrix protein vp40 of
      ebola virus.
AB  - Ebolavirus, a member of the Filoviridae family of negative-sense RNA viruses,
      causes severe haemorrhagic fever leading up to 90% lethality. Ebolavirus matrix
      protein VP40 is involved in the virus assembly and budding process. The RNA
      binding pocket of VP40 is considered as the drug target site for structure based
      drug design. High Throughput Virtual Screening and molecular docking studies were
      employed to find the suitable inhibitors against VP40. Ten compounds showing good
      glide score and glide energy as well as interaction with specific amino acid
      residues were short listed as drug leads. These small molecule inhibitors could
      be potent inhibitors for VP40 matrix protein by blocking virus assembly and
      budding process.

PMID- 23559748
TI  - Exploration of Sitagliptin as a potential inhibitor for the M1 Alanine
      aminopeptidase enzyme in Plasmodium falciparum using computational docking.
AB  - Plasmodium falciparum has limited capacity for de novo amino acid synthesis and
      rely on degradation of host hemoglobin to maintain protein metabolism and
      synthesis of proteins. M1 alanine aminopeptidase enzyme of the parasite involved
      in the terminal degradation of host hemoglobin was subjected to in silico
      screening with low molecular weight protease inhibitors. The km (avg) of the
      enzyme M1 alanine aminopeptidase for the substrate DL - Alanine beta Napthylamide
      Hydrochloride was estimated as 322.05uM. The molecular interactions between the
      enzyme and the substrate and the mechanism of enzyme action were analyzed which
      paved way for inhibition strategies. Among all the inhibitors screened,
      Sitagliptin was found to be most potent inhibitor with ki of 0.152 uM in its best
      orientation whereas the ki(avg) was 2.0055 uM. The ki of Sitagliptin is lower
      than the km of M1 alanine aminopeptidase for the substrate DL - Alanine beta
      Napthylamide Hydrochloride (322.05 uM) and Ki of the known inhibitor Bestatin.
      Therefore Sitagliptin may serve as a potent competitive inhibitor of the enzyme
      M1 alanine aminopeptidase of Plasmodium falciparum.

PMID- 23559749
TI  - Comparative analysis to identify determinants of changing life style in
      Thermosynechococcus elongatus BP-1, a thermophilic cyanobacterium.
AB  - A comparative genomics analysis among all forty whole genome sequences available
      for cyanobacteria (3 thermophiles- Thermosynechococcus elongatus BP-1,
      Synechococcus sp. JA-2-3B'a (2-13), Synechococcus sp. JA-3-3Ab and 37 mesophiles)
      was performed to identify genomic and proteomic factors responsible for the
      behaviour of T. elongatus BP-1, a thermophilic unicellular cyanobacterium with
      optimum growth temperature [OGT] of 55 degrees C. Majority of genomic and
      proteomic characteristics for this cyanobacterium indicated contrasting features
      indicating its mesophilic behaviour while the role of mutational biasness and
      selection pressure is thought to be responsible for high OGT. Contradictory
      results were obtained for T. elongatus for synonymous codon usage, CvP-bias and
      amino acid composition with respect to thermophilic behaviour. Calculated J2
      index is lowest among all cyanobacterial genomes. Except for proline and
      termination codons, T. elongatus showed synonymous codon usage pattern which is
      expected for mesophiles. Results indicated that among cyanobacterial genomes,
      majority of genomic and proteomic determinants put T. elongatus very close to
      mesophiles and the whole genome of this organism represents continuous gain of
      mesophilic rather than thermophilic behavior.

PMID- 23559750
TI  - Molecular docking study of P4-Benzoxaborolesubstituted ligands as inhibitors of
      HCV NS3/4A protease.
AB  - NS3/4A protease is an important emerging target for the cure of hepatitis C.
      There are many inhibitors of HCV NS3/4A protease that are passing through the
      clinical improvement indicating momentous reduction in the viral infection rate
      of patients. In this study molecular docking via MOE-Dock program was used to
      evaluate binding interactions of ligands with HCV NS3/4A protease. The docking
      and experimental results were found in good correlation. The best conformations
      of ligands were analyzed for binding interactions with the residues of binding
      cavity of NS3/4A protease. The valuable binding interactions and docking scores
      were observed for compounds 01, 05, 06, 07, 08 and 09.

PMID- 23559751
TI  - Virtual screening of compounds from the patchouli oil of Pogostemon herba for COX
      1 inhibition.
AB  - Our interest is to identify compounds from the patchouli oil of Pogostemon herba
      to inhibit the cyclooxygenase-1 (COX-1) enzyme activity. The data for the major
      compounds (alpha-patchouli alcohol isomer (CD521903, CD442384, and/or CD6432585),
      alphabulnusene, seychellene and alpha-guaiene) of patchouli oil were explored
      from the PubChem database. The compounds to COX-1 interactions were studied using
      the molecular docking tools Hex 6.12 and LeadIT2 Bisolve. The interactions were
      further visualized using the Chimera 1.7s viewer software tool. The analysis of
      the major compounds of patchouli oil showed that alpha-Patchouli alcohol
      (CD521903) binds to COX-1 at many active sites including: Leu223B, Asp228B,
      Leu237B, Arg332B, Trp138A, Glu139A, Ser142A, and Asn143A. Further analysis
      revealed that these binding sites are maintained by hydrogen bonds with Ser142A,
      Glu139A, and Asp228B. The interaction energy between COX-1 and alpha-patchouli
      alcohol (CD521903) is -6 kJ/mol (without solvent) and -15 kJ/ mol (with solvent
      DMSO). These theoretical data suggests alpha-patchouli alcohol as a potential
      inhibitor of the COX-1 enzyme. However, these observations should be investigated
      and confirmed using experimental evidence.

PMID- 23559752
TI  - PyPLIF: Python-based Protein-Ligand Interaction Fingerprinting.
AB  - Structure-based virtual screening (SBVS) methods often rely on docking score. The
      docking score is an over-simplification of the actual ligand-target binding. Its
      capability to model and predict the actual binding reality is limited. Recently,
      interaction fingerprinting (IFP) has come and offered us an alternative way to
      model reality. IFP provides us an alternate way to examine protein-ligand
      interactions. The docking score indicates the approximate affinity and IFP shows
      the interaction specificity. IFP is a method to convert three dimensional (3D)
      protein-ligand interactions into one dimensional (1D) bitstrings. The bitstrings
      are subsequently employed to compare the protein-ligand interaction predicted by
      the docking tool against the reference ligand. These comparisons produce scores
      that can be used to enhance the quality of SBVS campaigns. However, some IFP
      tools are either proprietary or using a proprietary library, which limits the
      access to the tools and the development of customized IFP algorithm. Therefore,
      we have developed PyPLIF, a Python-based open source tool to analyze IFP. In this
      article, we describe PyPLIF and its application to enhance the quality of SBVS in
      order to identify antagonists for estrogen alpha receptor (ERalpha).
      AVAILABILITY: PyPLIF is freely available at http://code.google.com/p/pyplif.

PMID- 23559754
TI  - Performance qualification: Critical to validation.

PMID- 23559753
TI  - Hepatitis E- Is it a risk to transfusion safety?

PMID- 23559755
TI  - Transfusion related complications in hemophilia.

PMID- 23559756
TI  - Evaluation of transfusion-related complications along with estimation of
      inhibitors in patients with hemophilia: A pilot study from a single center.
AB  - BACKGROUND: Apart from inhibitor development in patients with hemophilia (PWH)
      the old problems of blood borne viral infections and red cell alloimmunization
      still persist in PWH from developing countries. This study was planned to detect
      the presence of inhibitors in our PWH and to determine the presence of
      transfusion transmitted infections (TTI) markers and clinically significant red
      cell alloantibodies in these patients. MATERIALS AND METHODS: One hundred
      fourteen PWH were screened for various laboratory tests. Screening for inhibitors
      was done by mixing study. Blood grouping, TTI testing and red cell alloantibody
      detection were done as per the departmental standard operating procedures.
      RESULTS: Out of 114 patients evaluated 98(86%) had hemophilia A and remaining
      16(14%) had hemophilia B. Five (5.1%) patients of hemophilia A were positive on
      inhibitor screening. On Bethesda assay, one patient was high responder (14.4
      BU/ml) and rest 4 were low responders (<5 BU/ml). Overall, 19 PWH were positive
      for TTI markers and two had clinically significant red cell alloantibody (anti-E
      and anti-Jk(b)). CONCLUSION: This is probably first comprehensive study from our
      state on laboratory testing in PWH. The specialty of Transfusion Medicine can be
      a core part of hemophilia care. The overall prevalence of inhibitors in our
      hemophilia A patients was 5.1%, which is less as compared to majority of
      published studies.

PMID- 23559757
TI  - The effect of repeated freezing and thawing on levels of vitamin K-dependent
      coagulation factors and fibrinogen in fresh frozen plasma.
AB  - BACKGROUND: Fresh frozen plasma (FFP) is considered adequate for transfusion
      immediately after thawing or for up to 24 hours if kept at 1-6 degrees C, and is
      currently used very often to replace deficient clotting factors. If factor levels
      in refrozen FFP are within normal limits, then this component can possibly be
      transfused, thus avoiding wastage of FFP. AIM: To study the fate of vitamin K
      dependent coagulation factors (F II, F VII, F IX, F X) and fibrinogen activity
      levels in repeatedly (twice) frozen and thawed FFP. MATERIALS AND METHODS: Two
      hundred FFP units comprising 50 units of each major blood group (A, B, AB, and O)
      were thawed at 37 degrees C and 10-20 mL of FFP transferred to transfer bags with
      the help of a sterile connecting device (SCD). The FFP samples were taken into
      tubes (first sampling), and then the transfer bags were kept for 24 hours at 4
      degrees C. After 24 hours, repeat samples were taken in tubes from the transfer
      bag (second sampling), and then the bags were re-stored at < -18 degrees C. One
      week later, the above procedure was repeated. Activity of coagulation factors and
      fibrinogen levels were measured by the automated coagulation analyzer. RESULTS:
      The levels of F II, F VII, F IX, F X, and fibrinogen of all the 200 FFP units, at
      all four time points, were above the lower normal value, but well within the
      normal range. CONCLUSION: The levels of F II, F VII, F IX, F X, and fibrinogen
      remain stable and adequate for transfusion in twice-thawed-and-refrozen FFP. This
      component can be safely used for transfusion as a source of vitamin K-dependent
      clotting factors and fibrinogen.

PMID- 23559758
TI  - Frequencies and specificities of red cell alloantibodies in the Southern Thai
      population.
AB  - CONTEXT: Detailed reports of red cell alloantibody frequencies and specificities
      in the Thai population are limited. The aims of this study were to determine the
      specificity and compare the frequency of alloantibodies detected using column
      agglutination technology (CAT) and conventional tube techniques in blood donors
      and previously transfused patients. SETTINGS AND DESIGN: WE RETROSPECTIVELY
      REVIEWED ANTIBODY SCREENING AND IDENTIFICATION RECORDS FOR TWO TIME PERIODS:
      January-December 2006 during which conventional tube techniques were used and
      January 2008-December 2009 when CAT was used. RESULTS: The overall prevalence of
      alloantibodies in both patients and donors when using conventional tube
      techniques was 0.7%, for patients only was 0.9% and donors 0.6%. The most
      frequent antibodies detected in both groups were anti-Le(a), anti-Mi(a), anti
      Le(b), anti-P1 and anti-E. When using CAT, alloantibodies were found in 0.8% of
      patients and 0.13% of donors with the five most common alloantibodies found in
      patients were anti-Mi(a), anti-E, anti-Le(a), anti-c and anti-Le(b) respectively.
      Similarly the common alloantibody specificities in donors were anti-Le(a), anti
      Mi(a), anti-Le(b), anti-M and anti-D. CONCLUSIONS: One of the most commonly
      identified alloantibodies in the Thai population studied was anti-Mi(a)
      suggesting that Mia positive red cells should routinely be included in antibody
      screening and identification in this population. For antibody screening and
      identification, CAT method detected immune and warm alloantibody (ies) more
      frequently than that associated with conventional tube techniques.

PMID- 23559759
TI  - Serological investigation for hepatitis E virus infection in the patients with
      chronic maintenance hemodialysis from southwest of Iran.
AB  - BACKGROUND AND OBJECTIVES: A global distribution has been shown for hepatitis E
      virus (HEV) infection. Although the fecal-oral was considered as the primary
      infection route, there is controversial evidence for increased risk of the
      infection and consequent problems in patients on maintenance hemodialysis (HD)
      with suppressed immunity. The aim is to find if the prevalence of anti-HEV IgG,
      in patients with maintenance HD is higher than normal population in southwest of
      Iran. MATERIALS AND METHODS: During November and December 2010, in a cross
      sectional study we compared the seroprevalence of HEV among 80 patients with
      maintenance HD and 276 healthy individuals from Jahrom and Shiraz, Southwest of
      Iran. In addition to the clinical and laboratory records, serum samples were
      tested for the presence of IgG anti-HEV antibody by enzyme immunoassay (ELISA)
      test. The Chi-square, the Student's 't' and Fisher's exact tests were used for
      the statistical analysis. RESULTS: ELISA tests detected anti-HEV antibody in five
      males of the patients (6.3%) and in eight of the healthy controls (2.9%, 6 males
      and 2 female) which statistically were not different. The mean levels of the
      aspartate aminotransferase and the alanine aminotransferase in the sera of the
      patients were 19.96+/-11.08U/L and 23.93+/-14.26 IU/L, respectively. However, no
      one of the individuals with positive anti-HEV antibody showed elevated liver
      enzymes. Moreover, there was not a significant association between positive anti
      HEV antibody result, age and the history of the hemodialysis. CONCLUSIONS: We did
      not observe statistically significant higher anti-HEV prevalence among patients
      with chronic HD; however, more safety precaution is needed to keep HD patients
      from the risk of possible exposure to HEV infection.

PMID- 23559760
TI  - Prevalence of Diego blood group antigen and the antibody in three ethnic
      population groups in Klang valley of Malaysia.
AB  - BACKGROUND: Diego blood group antigen, Di(a), is very rare among Caucasians and
      Blacks, but relatively common among the South American Indians and Asians of
      Mongolian origin. The antibody to Di(a) is clinically significant to cause
      hemolytic disease in a new-born or hemolytic transfusion reaction. OBJECTIVES:
      This study was designed to determine the prevalence of Di(a) antigen among the
      blood donors from the three major ethnic groups in Klang Valley of Malaysia as
      well as to find an incidence of an antibody of the Diego antigen, anti-Di(a), in
      a tertiary care hospital to ascertain the need to include Di(a+) red cells for an
      antibody screen cell panel. MATERIALS AND METHODS: Serological tests were
      performed by column agglutination technique using commercial reagents and
      following instruction as per kit insert. RESULTS: Di(a) antigen was found with a
      frequency of 2.1% among the Malaysians donors in three ethnic groups viz, Malay,
      Chinese and Indian. It was present among 1.25% of 401 Malay, 4.01% of Chinese and
      0.88% of 114 Indian origin donors. None of the 1442 patients, including 703
      antenatal outpatients, had anti-Di(a) in serum. CONCLUSION: The prevalence of
      Di(a) antigen was found among the donors of all the three ethnic background with
      varying frequency. Inclusion of Di(a+) red cells in routine antibody screening
      program would certainly help in detection of this clinically significant antibody
      and to provide safe blood transfusion in the Klang Valley, though the incidence
      of antibody appears to be very low in the region.

PMID- 23559761
TI  - Removal of antibodies from red cells: Comparison of three elution methods.
AB  - BACKGROUND: Direct antiglobulin test (DAT) is the most common test done in
      immunohematology lab, which detects immunoglobulin and fragments of complement
      attached to the red blood cells. These coated red blood cells are difficult to
      accurately phenotype, which may be required for selection of appropriate unit of
      red blood cells for transfusion. AIMS: We have studied the efficacy of various
      elution methods in removing the antibodies coating the red cells and their impact
      on different blood group antigen activity. MATERIALS AND METHODS: Patient samples
      sent for serological evaluation of autoimmune hemolysis were included in the
      study. DAT and Indirect antiglobulin test (IAT) were performed using gel cards
      (ID system, DiaMed Switzerland). Antibody coated red cells, either by in-vivo or
      in-vitro sensitization, were used to assess the outcome of three elution methods.
      RESULTS: Out of 93 DAT positive samples already sensitized in vivo, 28 (30 %)
      samples became DAT negative post elution using either of three methods, while 36
      (38.8%) showed reduction in strength of reaction, whereas in 29 (31.2%) there was
      no change in strength of reaction. Similarly, out of the 17 samples prepared by
      in vitro sensitization, 12 samples became completely negative after glycine
      HCl/EDTA elution, 9 and 5 samples became negative after heat elution and
      chloroquine diphosphate elution methods, respectively. CONCLUSION: On comparative
      analysis glycine-HCl/EDTA elution method was better than the other two methods
      and can be used for eluting immunoglobulins from intact red cells.

PMID- 23559762
TI  - Blood transfusion among thalassemia patients: A single Egyptian center
      experience.
AB  - BACKGROUND: Although red cell transfusions are lifesavers for patients with
      thalassemia, they are responsible for a series of complications and expose the
      patients to a variety of risks. MATERIAL AND METHODS: This cross-sectional study
      included 464 Egyptian beta(beta) thalassemia major patients whose age ranged
      between 10 months and 31 years (mean 10.2 +/- 6.6 years). All patients were
      subjected to thorough history taking with special emphasis on blood transfusions
      regarding rate of blood transfusion, type of received blood, and history of
      previous transfusion reactions in addition to type of chelation and compliance to
      iron chelation therapy and history of diabetes. Serum ferritin and pretransfusion
      hemoglobin assessment were done for all patients. RESULTS: The mean
      pretransfusion hemoglobin level was 5.7 +/- 1.16 g/dl. Allergic reactions were
      observed in 3.9% of the patients during the period of the study, while the
      history of previous allergic reaction was given by 72% of the patients.
      Deferiprone showed better compliance (58.6%) than deferoxamine (26.3%). The
      prevalence of diabetes was 10.1% among the studied group. On comparing diabetics
      to nondiabetics, serum ferritin, transfusion intervals, and age were
      statistically higher among diabetics (P<0.001). CONCLUSION: Lower pretransfusion
      hemoglobin and high rate of prevalence of diabetes, in addition to better
      compliance to deferiprone than deferoxamine, were detected among the patients.

PMID- 23559763
TI  - Adverse events associated with apheresis procedures: Incidence and relative
      frequency.
AB  - INTRODUCTION: Apheresis procedures [Plateletpheresis, Plasmapheresis/ Therapeutic
      Plasma Exchange (TPE), & Peripheral Blood Stem Cell Collection (PBSC)] are
      usually well tolerated. Occasionally, Adverse Events (AEs) of variable severity
      may occur during or after the procedure. AEs that occur in Donors/Patients are
      divided into local reactions and systemic reactions. MATERIALS AND METHODS: A
      total of 3,367 apheresis procedures were performed, out of which 3,120 were
      plateletpheresis procedures, and out of which 1,401 were on Baxter CS 3000 &
      1,719 were on Haemonetics MCS+ cell separators. Rest of 247 TPE & PBSC procedures
      were done on Haemonetics MCS+ cell separators. RESULTS: 90 AEs were reported in
      relation to the 3,367 procedures. Out of 90 AEs, 85 AEs (94%) were associated
      with plateletpheresis (n = 3,120) and 05 AEs (06%) with TPE & PBSC (n = 247). The
      rate of vascular injury (VI), Citrate reaction (CR), and Presyncopal/Syncopal
      (PS/S) in plateletpheresis was 1.6% (52/3,120), 0.96% (30/3,120), and 0.096%
      (03/3,120), respectively. The rate of CR in TPE and PBSC was 1.23% (02/162) and
      2.3% (02/85), respectively. The rate of PS/S in PBSC was 1.17% (01/85). AEs for
      Plateletpheresis, TPE & PBSC were 2.7% (85/3,120), 1.23% (02/162), and 3.5%
      (03/85), respectively. VI, CR, and PS/S were mostly of mild intensity. Both cell
      separators were equally safe, when AEs associated with plateletpheresis were
      compared with each other; 2.8% on CS 3000 & 2.6% on MCS+. CONCLUSION: Apheresis
      procedures performed on cell separators are safe, with a low incidence of
      significant AEs. No significant difference was noted in AEs among the two cell
      separators studied.

PMID- 23559764
TI  - Increased preoperative collection of autologous blood with recombinant human
      erythropoietin therapy in tertiary care hospitals of Jammu.
AB  - INTRODUCTION: To study whether the administration of recombinant human
      erythropoietin increases the amount of autologous blood that can be collected
      before orthopaedic surgery. MATERIALS AND METHODS: We conducted a randomized
      controlled trial of recombinant human erythropoietin in 68 adults scheduled for
      elective orthopedic procedures. The patients received either erythropoietin 600
      units/kg of body weight or placebo intravenously every 5(th) day prior to each
      phlebotomy for 21 days during which time up to 5 units of blood was collected.
      Patients were excluded from donation when their hematocrit values were less than
      33%. All patients received iron sulphate 325mg orally 3 times daily. The mean
      number of units collected per patient was 4.33 +/- 0.4 for erythropoietin group
      and 3.05+/- 0.71 for the placebo group. RESULTS: The mean packed red cell volume
      donated by patients who received erythropoietin was 32% greater than that donated
      by patients who received placebo (196.3 vs. 169.4 ml, p<0.05). 68% in the placebo
      group and 9% of patients treated with erythropoietin were unable to donate >=4
      units. No adverse effects were attributed to erythropoietin. While participating
      in the study, complications developed in 2 patients one in each group
      necessitating their removal from the study. CONCLUSION: We conclude that
      recombinant human erythropoietin increases the ability of the patients about to
      undergo elective surgery to donate autologous blood units.

PMID- 23559765
TI  - HGV-HCV/HBV co-infection in India: A pilot study.
AB  - BACKGROUND: Hepatitis G virus (HGV) is newly identified virus, transmitted by
      infected blood and blood products. Effect of HGV infection on liver diseases is
      not well known. AIMS: Co-infection of HGV with hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infection has been reported however; very limited data is
      available from India. Therefore, we have performed a pilot study for the presence
      of co-infection of HGV in chronic liver disease patients. SETTING AND DESIGN: The
      study was performed in research laboratory at P.D. Hinduja National hospital and
      Medical research center, Mahim, Mumbai. Prospective study was designed. METHODS
      AND MATERIALS: Forty HBV, HCV related chronic liver disease patients were
      studied. Forty randomly selected voluntary healthy blood donors visiting our
      blood bank were included as controls. Serum bilirubin, alanine aminotransferase
      (ALT), Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were
      estimated. HGV infection was detected by using reverse transcriptase molony
      murine leukemia virus (M-MLV) with the help of HGV 340/625IC kit (Sacace, Italy).
      RESULTS AND CONCLUSION: One HCV positive patient had infection with HGV among 40
      HBV/HCV chronic liver disease patients.

PMID- 23559766
TI  - Effect of transfusion on dizziness in anemic patients after elective off-pump
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Neurological disorders are common complications following coronary
      artery bypass graft (CABG). Dizziness in convalescence period is of high
      importance because it can prolong patient's stay at the hospital and decrease in
      sense of rehealing. Transfusion indication is seen in hemoglobin levels <7 g/dl;
      however, dizziness has been frequently observed in patients with hemoglobin
      levels 7-10 g/dl and they have dramatic response to transfusion. Therefore, this
      study was designed to evaluate effect of transfusion on dizziness in hemoglobin
      levels of 7-10 g/dl to set a more accurate indication for transfusion in anemic
      patients after elective off-pump CABG. MATERIALS AND METHODS: This clinical trial
      study was conducted on 90 patients undergoing elective off-pump CABG surgery from
      January to June 2011, in Afshar cardiovascular center, Yazd, Iran. Patients with
      hemoglobin levels of 7-10 g/ dl measured 48 h after CABG were included in this
      study and those who stayed in ICU more than 48 h were excluded. The subjects were
      randomly divided into two groups: the experimental group received packed cell
      according to study protocol while the control group did not receive packed cell.
      Hemoglobin concentration was measured at 48 h and 72 h after CABG and discharge
      time, respectively. Dizziness was evaluated 72 h after surgery. Data were
      analyzed by ANOVA, Chi-square, and Fisher's exact test for quantitative and
      qualitative variables. RESULTS: The mean age of the patients was 63.5 +/- 10.67
      years, from all of patients in which 50 cases (55.6%) were males and 40 cases
      (44.4%) were females. Dizziness after surgery occurred in 35 cases (38.8%), of
      whom, 27 cases (62.8%) were in the control group and 8 cases (17%) were in the
      transfusion group. Significantly a difference in the incidence of dizziness was
      found between two groups (P= 0.001). CONCLUSION: Transfusion in hemoglobin levels
      of 7-10 g/dl can be useful to decrease dizziness in anemic patients after
      elective off-pump CABG; however, the guidelines in textbooks suggest transfusion
      after CABG to be in hemoglobin levels <7 g/dl.

PMID- 23559767
TI  - Seroprevalence of hepatitis C, hepatitis B and HIV viruses in hemophiliacs born
      1985-2010 in west Azarbaijan of Iran.
AB  - BACKGROUND: Although, in the past the risk of transfusion transmitted viral
      infections were high in hemophilia patients, but introduction of viral
      inactivation methods in1985,decreased the risk of human immunodeficiency and
      hepatitis C and B viruses transmission significantly. The aim of study was
      seroprevalence of hepatitis B surface antigen (HBs Ag), hepatitis C virus
      antibody (HCV Ab) and human immunodeficiency virus antibody (HIVAb) in
      hemophiliacs in west Azarbaijan of Iran, born in 1985-2010. MATERIALS AND
      METHODS: In a cross-sectional study, fifty patients with hereditary bleeding
      disorders born in 1985-2010, from total 250 patients who had been registered in
      Urmia Hemophilia Society were enrolled through the year 2010 to assess their
      seroprevalence for HCV Ab, HIV Ab and HBs Ag. Thirty five of 50 patients had
      hemophilia. Also; we performed a subset analysis for hemophilia patients.
      RESULTS: All 50 patients with hereditary bleeding disorders including 35 patients
      with hemophilia were seronegative for HIV Ab and HBs Ag. HCV-Ab was detected in
      serum of 3 of 50 (6%) patients with bleeding disorders. After subset analysis for
      hemophilia (A and B) patients, we found HCV infection in 8.57% (3 of 35) of
      hemophiliacs. CONCLUSION: In this study prevalence of HCV infection was very
      smaller than similar studies in Iran and other countries. This study shows the
      safety of using viral inactivated factor concentrates and recombinant factors
      after year 1985. None of Hemophiliacs were seropositive for HIV Ab and HBs Ag.

PMID- 23559768
TI  - Knowledge, attitude and practices of people towards voluntary blood donation in
      Uttarakhand.
AB  - INTRODUCTION: Blood transfusions form a crucial and irreplaceable part in the
      medical management of many diseases. The collection of blood from voluntary, non
      remunerated blood donors from low risk populations is an important measure for
      ensuring the availability and safety of blood transfusion. In a state like
      Uttarakhand which is visited by lakhs of visitors during pilgrimage season and
      where natural calamities and accidents are very common, the availability of blood
      is of utmost importance. AIM: To find out knowledge, attitude and practices of
      people towards voluntary blood donation to comprehend the situation and find ways
      to enhance voluntary blood donation in the state of Uttarakhand. MATERIALS AND
      METHODS: Multi stage methodology was designed to target population including
      general population, influencers (doctors) and supporting organizations (camp
      organizers, State AIDS Control Society Officials) who were subjected to in-depth
      interview using pre-structured questionnaires to assess knowledge/awareness about
      voluntary blood donation, factors preventing and source of knowledge about
      voluntary blood donation. RESULT: The sample population consisted of mostly men
      (67%) in the age-group of 26-35 years. Requirement of blood and the measures to
      promote voluntary blood donation have a direct relationship with the total
      population and literacy level of the population. Awareness about blood donation,
      source of knowledge about blood donation, reasons for not donating blood are
      particularly stressed. With increase in educational level, the awareness level
      was also found to increase. While among illiterates 81 percent of the respondents
      knew about blood donation, among the post graduates the same ratio was found to
      be almost cent-percent. Among various reasons cited for not donating blood, lack
      of awareness being the most common reason. People gathered information about
      blood donation from several different sources with electronic media being the
      most prominent. CONCLUSION: This study illustrates how increasing awareness and
      marketing 'Voluntary blood donation' can enhance adequacy of blood needs of a
      state or for that matter the entire country. This study also underlines how
      different media, especially electronic media, can be used to propagate altruistic
      blood donation.

PMID- 23559769
TI  - Analysis of efforts to maintain safe donor in main donor pool after completion of
      temporary deferral period.
AB  - BACKGROUND: Voluntary blood donation is not satisfactory all over India. In
      India, about 55% of donation is through voluntary non-remunerated blood donors
      (VNRBD). However, about one third already motivated blood donors are deferred due
      to stringent screening criteria, either temporarily or permanently. The
      temporarily deferred donors could be a good source of blood donation after
      deferral period. AIMS: The present study is carried out to know retrieval of
      blood donors those who are deferred temporarily. DESIGN: The present study is
      carried out in the Regional Blood Transfusion Centre of Western India. All donors
      screened as per the guideline and deferred donors are categorized as temporary
      and permanently deferred donors. MATERIALS AND METHODS: From temporarily deferred
      donors, reason for deferral is considered. As per reason of deferral, time
      duration for recalling the donor is defined. Based on this, donor is called back
      to donate again. STATISTICAL ANALYSIS: Chi-square test is applied. RESULT: A
      total of 33% donors were deferred either temporarily or permanently. In the
      repeat donors (5.32%) deferral rate was significantly higher than first time
      (1.32%) donors. Significant female preponderance was observed (15.05% vs 2.51%).
      Majority of temporarily deferred donors were less than 40 years of age (80.80%),
      graduate (82.90%), from low income group (62.90%) and profession was service
      (48.10%). CONCLUSION: Low hemoglobin (78.30%) was the most common reason of
      temporary deferral, both in first time and repeat donors (71.00%). Efforts to
      increase the hemoglobin in the repeat donors will improve the donor retention and
      overall blood safety can be increased.

PMID- 23559770
TI  - Perioperative use of allogenic blood components in live-related donor orthotopic
      liver transplantation: A cross sectional study.
AB  - BACKGROUND: In spite of many improvements that have reduced the blood component
      requirements, substantial numbers of transfusions are still needed in liver
      transplantation. AIMS: The objective of the present study was to analyze the
      perioperative usage of allogenic blood components and predict the preoperative
      factors as predictors of red cell transfusion in live-related donor liver
      transplant recipients. MATERIALS AND METHODS: The retrospective data on
      utilization of allogenic blood components were analyzed for a total of 150 liver
      transplant procedures. The data on utilization of blood components during surgery
      and till 48 hours of ICU stay was collected from the blood bank record and
      hospital information system (HIS). RESULTS: Red cell concentrate was commonest
      blood component used in liver transplant recipient and most of the transfusion
      took place during surgery. During intraoperative period 92.7% (N = 139) of the
      cases utilized red cell components with the median number of five whereas in
      postoperative period only 38% (N = 57) of patients received blood with the median
      number of one. This study demonstrates that the preoperative hemoglobin and
      platelet count are the predictors of utilization of red cell concentrates during
      surgery. There were a total of 11 (7.3%) recipients who didn't receive allogeneic
      blood transfusion in any form. Utilization of blood components was negligible
      among organ donors. CONCLUSION: Our study demonstrates the pattern and predictors
      of usage of allogeneic blood components in liver transplant recipients at a
      tertiary healthcare center in India.

PMID- 23559771
TI  - Hemovigilance program-India.
AB  - A centralized hemovigilance program to assure patient safety and to promote
      public health has been launched for the first time in India on Dec 10, 2012 in 60
      medical colleges in the first phase along with a well-structured program for
      monitoring adverse reactions associated with blood transfusion and blood product
      administration. National Institute of Biologicals (NIB) will be the National
      Coordinating Centre for Hemovigilance. This program will be implemented under
      overall ambit of Pharmacovigilance Program of India (PvPI), which is being
      coordinated by Indian Pharmacopoeia Commission (IPC). All medical colleges of the
      country will be enrolled in this program by the year 2016 in order to have a
      National Centre of Excellence for Hemovigilance at NIB, which will act as a
      global knowledge platform.

PMID- 23559772
TI  - Dyspnea with anemia turned out to be a case of hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant
      inherited disorder of the vascular system. It can be asymptomatic but when
      symptomatic most common presentation being epistaxis. It can involve any organs
      of the body like lungs, skin, liver brain, GI mucosa etc. We are reporting a case
      of HHT presented to us with dyspnea and severe anemia. He had arteriovenous
      malformations of different visceral organs and telangiectasia of skin along with
      presence of similar history in first-degree relatives.

PMID- 23559773
TI  - Thrombotic thrombocytopenic purpura in the first trimester of pregnancy.
AB  - Thrombotic thrombocytopenic purpura (TTP) occurs more commonly in women and so
      can be associated with pregnancy. The time during pregnancy with greatest risk
      for development of TTP is near term and during the post partum period. TTP
      occurring in early trimester is uncommon and is also associated with great
      maternal and fetal mortality. We report a successful outcome of pregnancy in a
      woman with TTP in early first trimester who was treated with therapeutic plasma
      exchange.

PMID- 23559774
TI  - IgE- and IgG mediated severe anaphylactic platelet transfusion reaction in a
      known case of cerebral malaria.
AB  - BACKGROUND: Allergic reactions occur commonly in transfusion practice. However,
      severe anaphylactic reactions are rare; anti-IgA (IgA: Immunoglobulin A) in IgA
      deficient patients is one of the well-illustrated and reported causes for such
      reactions. However, IgE-mediated hypersensitivity reaction through blood
      component transfusion may be caused in parasitic hyperimmunization for IgG and
      IgE antibodies. CASE REPORT: We have evaluated here a severe anaphylactic
      transfusion reaction retrospectively in an 18year-old male, a known case of
      cerebral malaria, developed after platelet transfusions. The examination and
      investigations revealed classical signs and symptoms of anaphylaxis along with a
      significant rise in the serum IgE antibody level and IgG by hemagglutination
      method. Initial mild allergic reaction was followed by severe anaphylactic
      reaction after the second transfusion of platelets. CONCLUSION: Based on these
      results, screening of patients and donors with mild allergic reactions to IgE
      antibodies may help in understanding the pathogenesis as well as in planning for
      preventive desensitization and measures for safe transfusion.

PMID- 23559775
TI  - Hemolytic disease of the fetus and newborn caused by anti-E.
AB  - OBJECTIVE: Maternal allo-antibody production is stimulated when fetal red blood
      cells are positive for an antigen absent on the mother's red cells. The maternal
      IgG antibodies produced will pass through the placenta and attack fetal red cells
      carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus
      and newborn caused by anti-E rarely occurs. CASE SUMMARY: We report two cases of
      anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis
      presenting with severe anemia, thrombocytopenia, and conjugated
      hyperbilirubinemia, while the other had moderate anemia and unconjugated
      hyperbilrubinemia. Although both the neonates were treated by phototherapy and
      intravenous immunoglobulin, one of them received double volume exchange
      transfusion. CONCLUSION: There appeared to be an increase in the occurrence of
      hemolytic disease of the fetus and newborn caused by Rh antibodies other than
      anti-D. In this case report, both patients presented with anemia and
      hyperbilirubinemia but were successfully treated, with a favorable outcome.

PMID- 23559776
TI  - Transfusion reaction in a case with the rare Bombay blood group.
AB  - Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in
      250,000. When individuals with the Bombay phenotype need blood transfusion, they
      can receive only autologous blood or blood from another Bombay blood group.
      Transfusing blood group O red cells to them can cause a fatal hemolytic
      transfusion reaction. In this study, we report a case with the rare Bombay blood
      group that was misdiagnosed as the O blood group and developed a hemolytic
      transfusion reaction. This highlights the importance of both forward and reverse
      typing in ABO blood grouping and standard cross-matching and performing standard
      pretransfusion laboratory tests in hospital blood banks.

PMID- 23559777
TI  - Antibodies against high frequency Gerbich 2 antigen (anti-Ge2): A real challenge
      in cross matching lab.
AB  - Transfusion management of patients' alloimmunized against high-prevalence
      erythrocyte antigens is often problematic in emergency situations. Gerbich (Ge)
      is very common blood group system and Gerbich-2 (Ge-2) antigen present in high
      frequency and outside Papua New Guinea population, Ge-2 negative population
      almost nil. To manage such kind of problems with real emergencies, implementation
      of rare donor registry program, cryopreservation of red cells of rare donors and
      biological cross matching to assess significance of these antibodies is
      warranted.

PMID- 23559778
TI  - Prevalence of weak D in northern hilly areas of Uttarakhand, India.

PMID- 23559779
TI  - Cough as presenting symptom in Dextran 40 hypersensitivity.

PMID- 23559780
TI  - Rapid diagnosis of heparin-induced thrombocytopenia using a particle gel
      immunoassay in at-risk cardiac surgery patients.

PMID- 23559781
TI  - Platelet antibodies detection: A limitation for Indian population.

PMID- 23559782
TI  - Workshop on development of teaching, training and assessment program for MD
      (transfusion medicine): A novel approach to Post Graduate Medical Education in
      India.

PMID- 23559783
TI  - New challenges for Ayurveda: How it will stand?

PMID- 23559784
TI  - Sushruta-samhitA - A critical Review Part-1 : Historical glimpse.
AB  - In the history of Ayurveda, Sushruta stands before Caraka. He practically applied
      Vaidika culture for treatment. His treatise translated into nine foreign
      languages apart from various Indian languages like Hindi, Bengali, Malayalam,
      etc., Sushruta is the most celebrated physician and surgeon in India. Though he
      practiced during the 5th century BC, many of his contributions to medicine and
      surgery preceded similar discoveries in the western world. Sushruta devotes a
      complete volume of his experiences to ophthalmologic diseases. In the Uttara
      Tantram, Sushruta enumerates a sophisticated classification of eye diseases
      complete with signs, symptoms, prognosis, and medical/surgical interventions. In
      particular, Sushruta describes what may have been the first extracapsular
      cataract surgery using a sharply pointed instrument with a handle fashioned into
      a trough. His ability to manage many common eye conditions of the time with
      limited diagnostic aids is a testament to his virtuosity.

PMID- 23559785
TI  - Self evolution: 1(st) domain of spiritual health.
AB  - While measuring physical, mental, and social health as defined by the World
      Health Organization (WHO), the basis of measurement is in terms of Determinants.
      Recently with the advent of health promotion activities, the emphasis is on
      enabling individuals, groups, and societies to have control on these
      Determinants. To measure the spiritual health, the 4(th) Dimension, a Spiritual
      Health Scale consisting of 3 Domains, 6 Constructs, and 27 Determinants of
      spiritual health were identified through a scientific process. A statistically
      reliable and valid Spiritual Health Scale (SHS 2011) containing 114 items has
      been developed. Construct validity and test-retest reliability has been
      established. The 3 Domains are: Self-Evolution, Self-Actualization, and
      Transcendence. In this article, the process of self evolution in terms of "Wider
      Perspective" and "Nurturance-Art" have been captured through the Determinants
      like Commitment, Introspection, Honesty, Creativity, Contemplation, Prayer,
      Philanthropy, Extending Self, Empathy, Yoga and Exercise, Questioning Injustice,
      Aesthetics, Value for Time, and Being Away From Comparisons.

PMID- 23559786
TI  - Medicinal and cosmetic uses of Bee's Honey - A review.
AB  - Bee's honey is one of the most valued and appreciated natural substances known to
      mankind since ancient times. There are many types of bee's honey mentioned in
      Ayurveda. Their effects differ and 'Makshika' is considered medicinally the best.
      According to modern scientific view, the best bee's honey is made by Apis
      mellifera (Family: Apidae). In Sri Lanka, the predominant honey-maker bee is Apis
      cerana. The aim of this survey is to emphasize the importance of bee's honey and
      its multitude of medicinal, cosmetic and general values. Synonyms, details of
      formation, constitution, properties, and method of extraction and the usages of
      bee's honey are gathered from text books, traditional and Ayurvedic physicians of
      Western and Southern provinces, villagers of 'Kalahe' in Galle district of Sri
      Lanka and from few search engines. Fresh bee's honey is used in treatment of eye
      diseases, throat infections, bronchial asthma, tuberculosis, hiccups, thirst,
      dizziness, fatigue, hepatitis, worm infestation, constipation, piles, eczema,
      healing of wounds, ulcers and used as a nutritious, easily digestible food for
      weak people. It promotes semen, mental health and used in cosmetic purposes. Old
      bee's honey is used to treat vomiting, diarrhea, rheumatoid arthritis, obesity,
      diabetes mellitus and in preserving meat and fruits. Highly popular in cosmetic
      treatment, bee's honey is used in preparing facial washes, skin moisturizers,
      hair conditioners and in treatment of pimples. Bee's honey could be considered as
      one of the finest products of nature that has a wide range of beneficial uses.

PMID- 23559787
TI  - A critical study of Rasamritam and it's applied aspects.
AB  - Historical studies of Rasa shastra reveal the use of metals and minerals, both
      for alchemical and therapeutical purposes in ancient past. But, gradually the
      alchemical use of the subject, declines and the therapeutical use takes over.
      Rasamritam is the latest doctrine in the field of Rasa shastra which compiles the
      extract of the older books and adopted some new and contemporary concepts. The
      practical aspects of this text influence both the academicians as well as
      physicians in large extent. Keeping the wealthier, timely concept of this text in
      mind, we are trying to review and analyze it critically for the benefit of
      researchers and practitioners and hope the idea will be fruitful.

PMID- 23559788
TI  - Applicability and importance of Caraka's concept of Aaturaparijnana Hetawah in
      understanding a patient.
AB  - Many concepts in Ayurveda are untouched or unexplored till date. One of such
      concepts to understand the healthy and unhealthy persons is that of the
      Aaturaparijnana Hetawah (APH), which is only mentioned in Caraka Samhita. The
      descriptions about Dushya, Desha, Bala, Kala, Prakriti, etc. are mentioned very
      briefly in all the classics. But no standard figure or pattern is maintained
      while considering them. It is only in the description of Aaturaparijnana Hetawah
      mentioned in Vimana Sthana that all the factors are pre-arranged in a
      chronological order to understand an individual according to one's Desha as from
      birth till grown up stage, and also to understand about the illness and most
      common disorders. In this article, it is aimed at presenting an in-depth
      evaluation about description of Aaturaparijnana Hetawah in Ayurveda. For this
      study, the references of Aturaparijnana Hetu have been collected through the
      Ayurvedic texts along with their commentaries. By making use of 14 factors
      described in Aaturaparijnana Hetawah, it is possible to have an in depth
      understanding about the patient's nature and factors that may be contributing to
      his health and illness. Aaturaparijnana Hetawah helps in an in-depth
      understanding of a patient's disease and heath status. More in-depth evaluation
      studies and application in the modern medical science should be done in order to
      avail the benefits of this approach.

PMID- 23559789
TI  - Pharmacological attribute of Aloe vera: Revalidation through experimental and
      clinical studies.
AB  - Aloe vera has long been used as a traditional medicine for inducing wound
      healing. It is a natural product that now a days is used in cosmetic industry.
      Benefits associated with Aloe vera have been attributed to the polysaccharides
      contained in the gel of the leaves though there are various indications for its
      use. Biological activities include promotion of wound healing, antifungal
      activity, anti-inflammatory, anticancer and immunomodulatory. Gingival
      fibroblasts play an important role in oral wound healing. Double blind-controlled
      trials are needed to determine its real efficacy in oral health.

PMID- 23559791
TI  - Clinical efficacy of Guduchyadi Medhya Rasayana on Senile Memory Impairment.
AB  - Aging has become one of the distinctive demographic phenomena in the 21(st)
      century and its social, economic and health implications are the most challenging
      issues. Senile Memory Impairment is a common condition characterized by mild
      symptoms of cognitive decline and occurs as a part of the normal aging process.
      It can be correlated to "Jarajanya Smrtibhramsha" according to Ayurveda. The
      present study deals with the efficacy of Guduchyadi Medhya Rasayana on Senile
      Memory Impairment. A total of 138 patients aged in between 55-75 years were
      registered and randomly divided into two groups as the trial and control groups.
      The drugs were administered for 3. The trial drug showed memory enhancement, anti
      stress, anti-depressant and anxiolytic properties. The trial group showed better
      results in the management compared to the control group.

PMID- 23559790
TI  - Safety and efficacy evaluation of Ayurvedic treatment (Arjuna powder and
      Arogyavardhini Vati) in dyslipidemia patients: A pilot prospective cohort
      clinical study.
AB  - Cardiovascular disease has multifaceted in which dyslipidemia, inflammation, and
      immunity play an important role. Arjuna powder and Arogyavardhini Vati used for
      centuries has potential for combating these factors. Therefore, the objective of
      this study was to evaluate the safety and efficacy of Ayurvedic treatment (Arjuna
      powder and Arogyavardhini Vati) for dyslipidemia patients. Total of 108 patients
      were screened at CGHS Ayurvedic Hospital, New Delhi. Ninety-six patients
      satisfied inclusion criteria, and signed informed consent and detailed medical
      history was recorded. Arjuna powder (5 g, BD) for 3 weeks and then Arogyavardhini
      Vati (500 mg, BD) for 4 weeks were prescribed to the patients. The primary
      efficacy endpoint was reduction in serum total cholesterol, LDL, triglycerides,
      and increased HDL levels. Secondary endpoints included reduction in serum C
      Reactive Protein (CRP) and blood glucose levels. Safety assessments included
      hepatic function (aminotransferase (ALT), aspartate transaminase (AST), alkaline
      phosphatase (ALP), bilirubin, and beta(2) microglobulin), renal function (urea
      and creatinine and NGAL) tests, and urine mercury level. The study was completed
      by 87 patients. The male and female patients were 65.5% (57/87) and 34.5%
      (30/87), respectively. There was a significant reduction in total cholesterol,
      LDL, triglycerides, CRP, and blood glucose. However, raised HDL level was also
      observed. Safety assessment results showed no significant change in serum ALT,
      AST, ALP and bilirubin, urea, creatinine beta(2) microglobulin, and NGAL levels
      at the end of study as compared to the baseline levels. In conclusion, the
      results of the present prospective cohort study showed that Ayurvedic treatment
      (Arjuna powder and Arogyavardhini Vati) is safe and effective for dyslipidemia.

PMID- 23559792
TI  - Development and validation of a Prototype Prakriti Analysis Tool (PPAT):
      Inferences from a pilot study.
AB  - Prakriti, for its tangible impacts upon decision making in Ayurvedic clinical
      practice, requires a thorough and fool-proof method of examination. Conventional
      methods adopted for Prakriti examination are found inconsistent with huge inter-
      and intra-rater inference variability. By observing the gaps in the field, the
      present study aims to develop a prototype Prakriti analysis tool and its
      evaluation on inter-rater validity grounds. The study observes that Vata and
      Pitta constructs of Prakriti identification in Ayurveda have a significant inter
      rater correlation (P ' 0.001 and P ' 0.01), whereas Kapha has less (P ' 0.02)
      correlation. It is inferred that for less correlated variables like those of
      Kapha, a better understanding is required to reach a better consensus.

PMID- 23559793
TI  - Clinical evaluation of the efficacy of Dashanga Kwatha Ghana Vati in the
      management of Urdhwaga Amlapitta (Non-ulcer dyspepsia).
AB  - A study has been designed to evaluate the effectiveness of Dashanga Kwatha Ghana
      Vati in Urdhwaga Amlapitta (non-ulcer Dyspepsia). Randomized single blind,
      placebo controlled study was conducted in 138 patients attending O.P.D. of
      department of Basic Principles, I.P.G.T. and R.A., Gujarat Ayurved University,
      Jamnagar, and grouped into two. Both the groups consumed two tablets of either
      Dashanga Kwatha Ghana Vati or placebo, twice daily after food for a period of
      eight weeks. The patients were followed upto four weeks, 110 patients had
      completed the treatment and no adverse effects were reported during the
      treatment. Both groups had improved in the clinical symptoms and overall
      statistical significance was observed in the differences of scores between the
      two groups.

PMID- 23559794
TI  - Clinical efficacy of Shodhana Karma and Shamana Karma in Mandala Kushtha
      (Psoriasis).
AB  - In India an estimated 0.8% of the population is suffering from Psoriasis. It is a
      papulo-squamous disorder of the skin, characterized by sharply defined erythemato
      squamous lesions. It is chronic and is well known for its course of remissions
      and exacerbations. The exact etiology is still unknown. This condition is
      comparable with Mandala Kushtha in Ayurvedic system of medicine. Shodhana
      procedures are reliable to control the disease. Forty patients, fulfilling the
      inclusion criteria, were selected and randomly divided into four groups with 10
      patients in each group. In Group A, Vamana and Virechana was administered once
      during the trial period. In Group B, Vamana and Virechana followed by Dermo-care
      in the dose of 5 g twice a day for the period of 2 months. In Group C, only Dermo
      care was administered. In Group D, Tab. Neotrexate (Methotrexate) 7.5 mg/week was
      given under the supervision of dermatologist. Marked improvement was observed in
      10% of the patients in Group B. Moderate improvement was observed in 20% of the
      patients in Group A, 90% in Group B, and 80% in Group D. Mild improvement was
      observed in 80% of the patients in Group A, 100% in Group C, and 20% in Group D.

PMID- 23559795
TI  - Clinical efficacy of Shankhapushpi and a herbo-mineral compound in type-II
      diabetes.
AB  - Diabetic population is more than 245 million worldwide and expected to be b380
      million by 2025. One of the main causes of increasing rate of diabetes is stress
      and tension in day-to-day life, disturbing the homeostasis of positive and
      negative emotions to initiate pathophysiology of stress-induced diabetes. In the
      present study, in Group A of 34 patients, a herbo-mineral compound containing
      Shuddha Shilajatu, Shuddha Guggulu, Vijayasara Ghana, Saptarangi Ghana, and
      Triphala Ghana was administered in the dose of 3 gm/day in three divided doses
      with luke-warm water before meal for the duration of 8 weeks, which significantly
      relieved symptoms (60.52%) like Prabhuta Mutrata (54.55%), Avila Mutrata
      (66.67%), Daurbalya (61.36%), Shrama (59.32%), etc. with fasting blood sugar
      (4.05%) and postprandial blood sugar (9.95%). In another series of 34 patients
      (Group B), where psychological health promoting drug Shankhapushpi was
      administered in the dose of 1.5 gm/day in three divided doses for 8 weeks along
      with herbo-mineral compound. The percentage relief was found to be more better on
      symptoms (71.13%) like Prabhuta Mutrata (76.92%), Avila Mutrata (83.33%),
      Daurbalya (75%), Shrama (70.37%), fasting blood sugar (18.04%) and postprandial
      blood sugar (27.75%). Group B showed better results on psychological parameters
      like disturbed Manasabhava (29.16%) and Brief Psychiatry Rating Scale (38.28%).
      The high significance of chi(2) (15.50) on overall effect of therapy indicated
      better results in group B.

PMID- 23559796
TI  - Clinical effect of Virechana and Shamana Chikitsa in Tamaka Shwasa (Bronchial
      Asthma).
AB  - To evaluate comparative efficacy of Samshodhana and Samshamana Chikitsa, the
      current study is planned in 24 patients of Tamaka Shwasa. Thirteen patients
      (Group A) were treated with Samshodhana, particularly with Virechana Karma. The
      patients of this group received Abhyantara Snehana with Tila Taila followed by
      Bahya Snehana with Tila Taila and Saindhava Lavana. After observations of proper
      signs of Snehana; Virechana Karma was performed with Aragvadha Phala Majja.
      Samsarjana Krama was followed for five days. Subsequently all the patients were
      given the trial drug (powder of Badara). The patients of group B, were treated
      only with the powder of dried ripe fruits of Badara. In both groups, the dose of
      Badara powder was 5 g, twice a day, with luke warm water, for a period of 60
      days. In group A, maximum number of patients (61.45 %) showed good response,
      while in group B, 45.45 % patients showed good response. No side effects were
      observed during the clinical trial. Based on the observations, it was concluded
      that, group A is more effective than group B.

PMID- 23559797
TI  - Effect of shatapushpa taila matra basti and pathadi kwatha on poly cystic ovarian
      disease.
AB  - Poly Cystic Ovarian Disease (PCOD) is a complex disorder affecting 5-15% women in
      their reproductive age and related to ovarian dysfunction, characterized by
      menstrual irregularities, hyperandrogonism, obesity, and infertility. In
      Ayurveda, these symptoms are found under various conditions, caused by vitiated
      Vata and Kapha. Pathadi Kwatha and Shatapushpa Taila Matra Basti were studied in
      the current attempt to evaluate their comparative efficacy in cases of PCOD.
      Total 34 patients of PCOD were registered among which, 32 had completed the
      treatment of 2 months. They were randomly divided in to three groups. In group A
      Pathadi Kwatha (10 g, bid) and Shatapushpa Taila Matra Basti (60 ml for 7 days
      after cessation of menses for 2 consecutive cycles) were administered. In group B
      only Basti, whereas in group C capsules of roosted wheat flour were administered.
      Better results were obtained in group A especially in menstrual irregularities,
      achieving follicular growth and in weight reduction.

PMID- 23559798
TI  - Clinical efficacy of Shiva Guggulu and Simhanada Guggulu in Amavata (Rheumatoid
      Arthritis).
AB  - Amavata is the second most common joint disorders. Nowadays erroneous dietary
      habits, lifestyle and environment have led to various autoimmune disorders i.e.
      Amavisajanya Vikaara and Amavata is one among them. Rheumatoid arthritis can be
      correlated with Amavata in view of its clinical features. Many research studies
      have been done to solve this clinical enigma, but an effective, safe, less
      complicated treatment is still required for the management of Amavata. In the
      present study, 24 patients of Amavata were registered and randomly grouped into
      two. In group A, Shiva Guggulu 6 g/day in divided doses and in group B, Simhanada
      Guggulu 6 g/day in divided doses were given for 8 weeks. On analysis of the
      results, it was found that Simhanada Guggulu provided better results as compared
      to Shiva Guggulu in the management of Amavata.

PMID- 23559799
TI  - Clinical efficacy of two different samples of Shirishavaleha in Tamaka Shwasa
      (Bronchial Asthma).
AB  - Incidences of Bronchial Asthma have been raised in recent decades due to
      increased industrialization and pollution. This miserable condition can be
      compared with Tamaka Shwasa in Ayurveda. Modern synthetic drugs will provide
      instant relief in these cases, but are tend to develop a number of adverse drug
      reactions. Knowing this, the current suffering population is looking towards few
      remedies from other systems of medicines, that are comparatively safe and provide
      better relief. Shirisha [Albizzia lebbeck Benth] is a drug with multi-dimensional
      activities emphasized in Ayurveda for different disease conditions. Considering
      this, two types of Shirishavaleha (confection of Shirisha) were prepared by
      Kwatha (decoction) of Twak (bark) and Sara (heartwood) of Shirisha to evaluate
      its comparative efficacy in Tamaka Shwasa (bronchial asthma). The results were
      assessed in terms of clinical recovery, symptomatic relief and pulmonary function
      improvement. A significant increase in Hb and considerable decrease in total
      eosinophil count, AEC and ESR were observed. The study revealed that
      Shirishavaleha can be used as an effective drug in bronchial asthma.

PMID- 23559800
TI  - Clinical efficacy of Jalaukawacharana (leech application) in Thrombosed piles.
AB  - 'Arsha' (hemorrhoids) is an ailment that affects all economical groups of
      population. Though the disease is within the limits of management, it has its own
      complications like severe hemorrhage, inflammation, and thrombosis, by which a
      patient gets severe pain and is unable to continue his routine work. Prior to
      surgical treatment of hemorrhoids, associated conditions like inflammation,
      strangulation, thrombosis, etc. need to be managed. Thrombosed piles possibly
      occur due to high venous pressure associated with severe anal pain. Leech
      (Hirudina medicanalis) application is found to be effective in reducing pain. In
      thrombosed piles, leech application has shown thrombolytic action, which
      contributes in re-establishment of circulation. It is observed in the study that,
      pus and mucous discharge have been reduced after leech application; which may be
      due to antimicrobial and mucolytic properties of leech. This method of treatment
      is found to be effective and increase the quality of life in patients suffering
      with thrombosed piles.

PMID- 23559801
TI  - Critical study of Jara (aging) and its management.
AB  - Jara Avastha (stage of old age) is the later phase of life in which maximum
      decline of bodily elements is observed. Paramanuvibhaga (cell division) takes
      place at every moment; particularly in old age, it will be fast in comparison
      with other phases of life. Some organ related changes also take place during this
      period, which are the decades of Balya, Vridhhi, Chhavi, Medha, Twak, etc., In
      this study, applied aspects of Medha Hani, Twak Hani, and Drishti Hani were
      evaluated subjectively as well as objectively. Patients were selected from the
      OPD of Department of Basic Principles, I.P.G.T. and R.A., Gujarat Ayurved
      University, Jamnagar, irrespective of their sex, caste, religion, etc., and
      randomly divided into two groups. Patients in Group A were treated with
      Panchagavya Ghrita and Group B with plain Go Ghrita for 90 days and the dose of
      drug was 10 g/day at Nirannakala (early morning with empty stomach). Both groups
      showed significant results, the difference in between the groups is statistically
      insignificant.

PMID- 23559802
TI  - Urushiol-induced contact dermatitis caused during Shodhana (purificatory
      measures) of Bhallataka (Semecarpus anacardium Linn.) fruit.
AB  - Bhallataka (Semecarpus anacardium Linn.; Ancardiaceae) is mentioned under
      Upavisha group in Ayurvedic classics and it is described as a poisonous medicinal
      plant in Drugs and Cosmetics Act (India), 1940. Fruit of Bhallataka is used
      either as a single drug or as an ingredient in many compound formulations of
      Indian systems of medicine to cure many diseases. Tarry oil present in the
      pericarp of the fruit causes blisters on contact. The major constituent of the
      tarry oil is anacardic acid and bhilawanol, a mixture of 3-n-pentadec(en)yl
      catechols. Bhilawanol A and B are known as Urushiols, and also, anacardic acid is
      closely related to Urushiol. Urushiol-induced contact dermatitis is the medical
      name given to allergic rashes produced by the oil Urushiol. This paper deals with
      five case reports of contact dermatitis caused during different stages of
      Shodhana (purificatory measures) of Bhallataka fruit due to improper handling of
      the utensils and disposal of media used in Shodhana procedure and their Ayurvedic
      management. To combat these clinical conditions, the affected persons were
      advised external application with pounded Nimba (Azadirachta indica A. Juss.)
      leaves on the affected parts and internal administration of Sarivadyasava 30 ml
      thrice daily after food and Triphala Churna 5 g before food twice daily.
      Reduction of itching and burning sensation was observed after topical
      application.

PMID- 23559803
TI  - Pharmacognostical and analytical study of Tulsi-Amla-Yasti Ghrita.
AB  - Tulasi Amla Yashti Ghrita is an Ayurvedic formulation, which is beneficial in the
      management of the side effects of Head and Neck Malignancies induced by
      Radiotherapy and Chemotherapy. A pharmacognostical study involving both the
      macroscopic and powder microscopy of raw drugs of Tulasi Amla Yashti Ghrita and a
      physicochemical analysis of the finished product were carried out, to evaluate
      the quality of the formulation. The specific gravity of the formulation was
      0.9130 and pH was 3.5. Thin layer chromatography (TLC) and high performance thin
      layer chromatography (HPTLC) were carried out after organizing the appropriate
      solvent system, in which five spots were distinguished in TLC and nine spots in
      HPTLC. Most of the Rf values for the spots observed were identical. The
      observations could be considered to be the reference standards in future studies.

PMID- 23559804
TI  - Development of Random Amplified Polymorphic DNA markers for authentification of
      Cissus repanda vahl.
AB  - Cissus repanda Vahl. belongs to the family Vitaceae, commonly known in Hindi as
      "Panivel," is a large climber distributed all over India. The crushed or powder
      of root is prescribed by tribal people and traditional medical practitioners of
      Orissa for its healing properties in cases of bone fracture, cuts and wounds,
      swellings, and so on. In spite of its reputation, its leaves have not been
      investigated scientifically. The present study deals with pharmacognostical and
      molecular characterization by Random Amplified Polymorphic DNA (RAPD) markers and
      their role in laying down standardization and pharmacopoeial parameters. Genomic
      isolation of DNA from fresh leaves was amplified by RAPD markers. The diagnostic
      characters are mucilage, calcium oxalate rosette crystals, spiral vessels, and
      fibers. The unique bands obtained in Polymerase Chain Reaction (PCR)
      amplification clearly discriminated having, many bright and light bands
      indicating the genuinity of the plant. RAPD may serve as a complementary tool in
      quality control of many herbal sources.

PMID- 23559805
TI  - Pharmacognostical and phytochemical studies of Curcuma neilgherrensis (Wight)
      leaf - A folklore medicine.
AB  - Curcuma neilgherrensis Wight is a folk medicinal plant used in the management of
      diabetes mellitus. The leaves of this herb are said to be successful in managing
      high blood glucose levels. This study is aimed at assessing the scientific
      appraisal of C. neilgherrensis in the course of pharmacognostical characters and
      phytochemical parameters, as these are not yet been done. Pharmacognostic study
      mainly covered the macroscopic and microscopic features of the leaves including
      powder microscopy, and revealed the presence of trichomes, spiral vessels etc.
      Phytochemical parameters such as pH, total ash value, water-soluble extract and
      MeOH extract values were assessed in the preliminary physicochemical screening.
      Qualitative analysis revealed the existence of certain chemical constituents such
      as flavonoids, tannins, organic acids and saponin glycosides. The crude extract
      of leaves was subjected to TLC and HPTLC for the separation of components.

PMID- 23559806
TI  - Analytical profile of Brahmi Ghrita: A polyherbal Ayurvedic formulation.
AB  - Brahmi Ghrita, a polyherbal Ayurvedic formulation is recommended in the
      management of various psychological disorders like Unmada, Apasmara and
      Graharogas. The present study deals with the pharmacognostical identification of
      ingredients of Brahmi Ghrita and its physico-chemical analysis. Pharmacognostical
      study containing both macroscopic and powder microscopy of raw drug revealed the
      quality and genuineness of all the constituents of Brahmi Ghrita. Organoleptic
      features of coarse powder made out of the crude drugs were within the standards
      prescribed. Acid value was 0.16075, saponification value 184.17, Refractive Index
      value 1.467 at room temperature, Iodine value 26.715, Specific gravity at room
      temperature was 0.9133. HPTLC was carried out after organizing appropriate
      solvent system in which maximum 9 spots were distinguished and most of the Rf
      values were identical in alcoholic extract which shows the presence of certain
      definite constituents in Brahmi Ghrita.

PMID- 23559807
TI  - Pharmaceutical standardization of Mamajjaka (Enicostemma littorale Auct. non Bl)
      Ghana.
AB  - Mamajjaka (Enicostemma littorale Auct. non Bl) is a well known folklore medicine
      frequently used for the treatment of Madhumeha (diabetes mellitus). There is no
      direct reference available for its antihyperglycaemic activity in Ayurvedic
      classics. Considering this, a study is planned towards developing pharmaceutical
      standardization of Mamajjaka Ghana. In this study, five batches of Mamajjaka
      Ghana were prepared and findings were systematically recorded to maintain the
      Standard Operating Procedure (SOP). An average of 14.78% Ghana was obtained. The
      physico-chemical parameters, qualitative test for various functional groups,
      quantitative estimation of total alkaloids, HPTLC profile, heavy metal analysis
      and microbial overload were carried out of Mamajjaka Ghana.

PMID- 23559808
TI  - In vitro antimicrobial and brine shrimp lethality of Allophylus cobbe L.
AB  - Plants are rich source of pharmacologically active agents, which could be
      explored in disease management. Methanol, ethanol, and petroleum ether extracts
      of the whole plant of Allophylus cobbe L. were evaluated for antimicrobial and
      cytotoxic activities. In vitro antimicrobial sensitivity by disk diffusion method
      was conducted against four Gram-positive and seven Gram-negative pathogenic
      bacteria and seven fungi. In the antibacterial and antifungal sensitivity tests,
      growth inhibition was found to be within the range of 10.0-17.67 mm. Strong zone
      of inhibition by the ethanol extract of A. cobbe (EEAC) was found against
      Trichophyton spp. With some exceptions, a mild to strong antimicrobial activity
      was observed in this study. Significant minimum inhibitory concentration (MIC;
      15.625 MUg/ml) was found against Trichophyton spp. Other detected MICs were
      within the range of 31.25-125 MUg/ml. The petroleum ether extract of the plant
      exhibited strong cytotoxicity in the brine shrimp lethality bioassay test.

PMID- 23559809
TI  - Toxicological evaluation of Panchakola Avaleha, an Ayurvedic classical
      formulation, in albino rats.
AB  - The present study was carried out to assess the safety of standardized Panchakola
      Avaleha on albino rats (Wistar strain). Animals were administered three doses of
      Panchakola Avaleha by oral routes, viz. higher (500 mg/kg/day), middle (250
      mg/kg/day), and therapeutic dose (50 mg/ kg/ day) for 28 consecutive days.
      Effects of the test drug on hematological, biochemical, and histopathologic
      parameters were evaluated. This study revealed normal behavior, no mortality, and
      no significant changes in hematological, biochemical, and histopathological
      examinations.

PMID- 23559810
TI  - Anti-inflammatory activity of two varieties of Pippali (Piper longum Linn.).
AB  - The present study has beenundertaken to evaluate the anti-inflammatory activity
      of two varieties of Pippali in acute and sub-acute experimental models of
      inflammation in albino rats. Four different market samples of each variety of
      Pippali were procured from different regions of India. The samples collected from
      South India which have given more extractive values were selected for screening
      of anti-inflammatory activity. Randomly selected animals were divided into four
      groups of six animals each. The test drugs were administered orally at a dose of
      200 mg/kg and the activity was compared with standard anti-inflammatory drugs in
      both models. Among the two different test samples studied, it was found that
      Chhoti variety of Pippali suppressed inflammation of both acute and sub acute
      phase, while Badi variety of Pippali only of acute phase. Thus for the
      therapeutic utility, Chhoti variety of Pippali may be considered over the Badi
      variety.

PMID- 23559811
TI  - Effect of fennel on pain intensity in dysmenorrhoea: A placebo-controlled trial.
AB  - The aim of this study was to determine the clinical effect of Foeniculum vulgare
      on primary dysmenorrhoea. Sixty virgin girls with complaints of dysmenorrhoea
      were enrolled in this study, out of which 50 cases were completed the course of
      treatment and were divided in two groups (study and placebo) and were under
      treatment for two cycles. In study group a capsule of 30 mg fennel extract, four
      times a day for three days from start of their menstrual period and in placebo a
      capsule containing wheat flour in same dose was administered. Intensity of pain
      was reported by using a 10 - point linear analogue technique. In study group the
      mean age of menarche was 13.1 +/- 0.1 and onset age of dysmenorrhoea was 14.5 +/-
      0.1 years. Both groups were relieved but there was significant difference between
      study and placebo group. Study group shown more effective results than placebo in
      pain relief (P'0.05). Based on the observations, it can be concluded that, fennel
      is an effective herbal drug for menstrual pain.

PMID- 23559812
TI  - Anti-ulcer activity of Lucer against experimentally induced gastric ulcers in
      rats.
AB  - The present study is designed to explore the mechanism of action of herbal
      formulation Lucer against experimentally induced gastric ulcers. The aqueous
      extract (120 and 180 mg/kg) of Lucer was tested against aspirin and ethanol
      induced gastric ulcer model in rats. The drug has been found to be very effective
      in inhibiting gastric ulceration. This is evident from reduction in ulcer index
      parameters. Besides, significant reduction in acid secretory parameters such as
      total acidity, total acid output and volume of gastric secretion were also
      observed. It is concluded from this study that the drug possesses anti-ulcer
      activity in both the models. The anti-ulcer activity of the drug can be
      attributed to inhibition of acid secretary parameters and strengthening of
      gastric mucosal barrier.

PMID- 23559813
TI  - Effect of Majja Basti (therapeutic enema) and Asthi Shrinkhala (Cissus
      quadrangularis) in the management of Osteoporosis (Asthi-Majjakshaya).

PMID- 23559814
TI  - Aerobic isotonic exercise and Prameha (diabetes mellitus) as per Prakriti.

PMID- 23559815
TI  - Water purification.

PMID- 23559816
TI  - Journal of Pharmacy and BioAllied Sciences, January 2013.

PMID- 23559817
TI  - Clinical research regulation in India-history, development, initiatives,
      challenges and controversies: Still long way to go.
AB  - The Central Drugs Standard Control Organisation and its chairman Drug Controller
      general of India are bequeathed to protect the citizens from the marketing of
      unsafe medication. The startling findings, of the 59(th)report of the
      Parliamentary Standing Committee on Health and Family Welfare, have uncovered the
      lax standards followed by the regulatory authorities in India. The growing
      clinical research after the product patents rights for the pharmaceutical
      industries as per the trade related aspects of intellectual property rights
      agreement and adverse drug reaction monitoring of the marketed drugs have raised
      many ethical and regulatory issues regarding the promotion of new drugs in Indian
      markets. Many controversial group of medicines; unauthorised and irrational FDCs
      not relevant to India's medical needs, are available which are not sold in any of
      the countries with matured regulatory bodies. It becomes vital to understand the
      history, growth and evolution of the regulatory aspects of drugs which are
      handled by multiple Ministries and Departments of the Government of India.
      Although amendment to Schedule Y, registration of Contract Research
      Organisations, registration of Clinical Trials, Speeding up review process,
      Pharmacovigilance (PhV) programme for India and Inspection of clinical trial
      sites have been started by the various regulatory agencies. However due to casual
      approach in marketing approval for sale of the drugs, the unethical steps taken
      by some pharmaceutical companies and medical practitioners has reiterated the
      need to get appropriate understanding of present regulation of drugs and clinical
      research especially regarding the practical rules and regulations.

PMID- 23559818
TI  - The potential anesthetic threats, challenges and intensive care considerations in
      patients with HIV infection.
AB  - Acquired immunodeficiency syndrome (AIDS) has become a pandemic with ever looming
      danger of its transmission in health professionals. The number of AIDS patients
      has increased tremendously over the last two decades, who present for surgical
      procedures as well as who get admitted in intensive care unit for their critical
      condition. As such anesthesiologists and intensivists are exposed to potential
      risk of disease transmission on a daily basis from such patients. The guidelines
      and protocols formulated in the western world regarding prevention of disease
      transmission cannot be applied uniformly in the developing nations, such as India
      due to various factors and limitations. As such there is a continuous need felt
      in this arena to prevent the catastrophic consequences of AIDS in our medical
      fraternity while treating such patients in operation theatres and critical care
      units. This study reviews the various pathophysiological aspects, anesthetic
      considerations, intensive care implications, and various areas where current
      knowledge about AIDS can be applied to prevent its potential transmission in high
      risk clinical groups.

PMID- 23559819
TI  - Phytochemical and pharmacological potential of Acanthus ilicifolius.
AB  - Acanthus ilicifolius (Acanthaceae) has received considerable attention due to its
      wide range of secondary metabolites and its traditional usage in Indian and
      Chinese system of medicine. This plant is reported to be a mangrove. Mangrove
      survives in the most hostile environment with fluctuating tidal and saline
      regime. Hence, these plants are considered to be rich sources of steroids,
      triterpenoids, saponins, flavonoids, alkaloids, and tannins. Present review
      article is an attempt to cover recent developments in phytochemical and
      pharmacological potential of drug. Traditionally, the plant has been used for
      dyspepsia, paralysis, asthsma, headache, rheumatism, and skin diseases. The plant
      is known as 'Krishnasaireyaka' or 'Karimkurunji', is one of the 9 plants equated
      to the drug 'Sahachara,' which is used in Ayurvedic medicine for rheumatic
      complaints. The plant has not been explored to its full potential. The review
      will be a good reference tool for investigators who wish to work on natural
      compounds with free radical scavenging activity to combat diseases associated
      with stress.

PMID- 23559820
TI  - Chitinases: An update.
AB  - Chitin, the second most abundant polysaccharide in nature after cellulose, is
      found in the exoskeleton of insects, fungi, yeast, and algae, and in the internal
      structures of other vertebrates. Chitinases are enzymes that degrade chitin.
      Chitinases contribute to the generation of carbon and nitrogen in the ecosystem.
      Chitin and chitinolytic enzymes are gaining importance for their biotechnological
      applications, especially the chitinases exploited in agriculture fields to
      control pathogens. Chitinases have a use in human health care, especially in
      human diseases like asthma. Chitinases have wide-ranging applications including
      the preparation of pharmaceutically important chitooligosaccharides and N-acetyl
      D glucosamine, preparation of single-cell protein, isolation of protoplasts from
      fungi and yeast, control of pathogenic fungi, treatment of chitinous waste,
      mosquito control and morphogenesis, etc. In this review, the various types of
      chitinases and the chitinases found in different organisms such as bacteria,
      plants, fungi, and mammals are discussed.

PMID- 23559821
TI  - Current interventions in the management of knee osteoarthritis.
AB  - Osteoarthritis (OA) is progressive joint disease characterized by joint
      inflammation and a reparative bone response and is one of the top five most
      disabling conditions that affects more than one-third of persons > 65 years of
      age, with an average estimation of about 30 million Americans currently affected
      by this disease. Global estimates reveal more than 100 million people are
      affected by OA. The financial expenditures for the care of persons with OA are
      estimated at a total annual national cost estimate of $15.5-$28.6 billion per
      year. As the number of people >65 years increases, so does the prevalence of OA
      and the need for cost-effective treatment and care. Developing a treatment
      strategy which encompasses the underlying physiology of degenerative joint
      disease is crucial, but it should be considerate to the different age ranges and
      different population needs. This paper focuses on different exercise and
      treatment protocols (pharmacological and non-pharmacological), the outcomes of a
      rehabilitation center, clinician-directed program versus an at home directed
      individual program to view what parameters are best at reducing pain, increasing
      functional independence, and reducing cost for persons diagnosed with knee OA.

PMID- 23559822
TI  - Synthesis and PASS-assisted in silico approach of some novel 2-substituted
      benzimidazole bearing a pyrimidine-2, 4, 6(trione) system as mucomembranous
      protector.
AB  - PURPOSE: The present paper demonstrates the utility of PASS computer-aided
      program and makes a clear comparison of predicted and observed pharmacological
      properties of some novel 5-[(2E)-1-(1H-benzimidazol-2-yl)-3-substituted
      phenylprop-2-en-1-ylidene] pyrimidine-2, 4, 6 (1H, 3H, 5H)-triones (5a-f).
      MATERIALS AND METHODS: The synthesis of the titled derivatives were achieved by
      the reaction between 2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-ones (4a-f)
      and barbituric acid in the presence of catalytic amount of acetic acid medium.
      All the final structures were assigned on the basis of IR, (1)HNMR and mass
      spectra analysis. All the newly synthesized compounds were screened for their
      antiulcer activity in the pylorus-ligated rats. RESULTS: Compounds 5b, 5e and 5c
      showed a percentage protection of (69.58, 69.56 and 67.17 at a dose of 50 mg/kg
      b.w.) when compared to standard omeprazole (77.37%, 2 mg/kg b.w.). CONCLUSION:
      Scanning of stomach specimens using electron microscope revealed that the mice
      treated with standard and synthetic derivatives had no injury observed in stomach
      mucosa, which is identical to that of the control animal.

PMID- 23559823
TI  - Determination of cyclamate in urine by derivatized gas chromatography-mass
      spectrometry.
AB  - AIM: It is important in toxicological/drug screening work to rule out the
      possible interfering analytes, to eliminate the false positive or negative
      results. In this paper, we describe a simple, selective, and sensitive
      derivatized GC-MS method for the determination of cyclohexylsulfamic acid
      (cyclamate) in urine. MATERIALS AND METHODS: Elite- 5MS capillary column was used
      for the separation of analytes and detection using GC-MS. The analysis was
      carried out in selected ion monitoring mode (SIM) in the range of 26 to 200 using
      m/z values of 57, 30, 55, 41, 44, 67, 82, 98, and 39. RESULTS AND DISCUSSION: The
      method is based on the conversion of cyclamate into nitroso derivative of
      cyclamate followed by its gas chromatography-mass spectrometry determination. The
      limit of detection, limit of quantitation, and linearity range of the proposed
      method were found to be 0.2 MUg/ ml, 0.7 MUg/ml, and 1-15 MUg/ml, respectively.
      The recovery of the present method is in the range of 88-94%. CONCLUSION: The
      proposed method can be applied for detection and quantification of cyclamate in
      urine.

PMID- 23559824
TI  - Quantitative determination of imatinib stability under various stress conditions.
AB  - OBJECTIVE: A simple, rapid, reverse phase and stability-indicating high
      performance liquid chromatography (HPLC) method for the estimation of imatinib in
      solution and in plasma under forced degradation conditions was developed.
      MATERIALS AND METHODS: The method employed isocratic elution using a Waters
      Atlantis C18 (5 MU, 4.6 mm * 150 mm) HPLC column. The mobile phase consisted of
      acetonitrile and 10 mM KH2PO4 buffer in the ratio of 35:65 (v/v, pH = 4.6), which
      was delivered using isocratic flow at a rate of 1 mL/min. The injection volume of
      50 MUL and imatinib was monitored using UV detection 270 nm after a clean-up step
      with diethyl ether and with a total run time of 6 min. RESULTS: The method was
      validated in solution as well as in plasma, and the response was found to be
      linear in the concentration range of 0.5-20 MUg/mL. The coefficient of
      correlation was found to be >0.99. Forced degradation studies revealed that
      imatinib undergoes degradation under different stress conditions. DISCUSSION: The
      developed HPLC method could effectively resolve degradation product peaks from
      imatinib except at neutral pH. Further, no interference was found at the
      retention time of imatinib from any plasma components, indicating selectivity of
      the developed method. The limits of detection and quantitation of the method were
      0.025 and 0.5 MUg/mL, respectively.

PMID- 23559825
TI  - Grewia gum as a potential aqueous film coating agent. I: Some physicochemical
      characteristics of fractions of grewia gum.
AB  - BACKGROUND: Grewia gum has received attention as a polymeric pharmaceutical
      excipient in the recent times, being employed as a suspending, film coating,
      mucoadhesive, and binding agent. The low aqueous solubility, however, has limited
      its characterization and application. OBJECTIVE: The purpose of this study was to
      fractionate and evaluate some physicochemical properties of the gum. MATERIALS
      AND METHODS: Aqueous dispersion of the gum was treated at 80 degrees C for 30 min
      in the presence of sodium chloride and was subsequently fractionated by
      successively centrifuging it at 3445 rpm for 30 min. Skeletal density,
      solubility, particle size, and rheological as well as thermal characteristics of
      the fractions were evaluated. The (1)H nuclear magnetic resonance (NMR) and near
      infrared (NIR) profiles of the fractions were also investigated. The solubility
      of the gum increased up to fourfold while the viscosity decreased from 244 to as
      low as70 cP at 40 rpm with some fractions. RESULTS: Grewia gum and the fractions
      showed good thermal stability exhibiting no thermal events, but charred
      irreversibly at 297 degrees C irrespective of the fraction. The molecular weight
      averages by weight and by number of the fractions were between 233,100 and
      235,000. The (1)H nuclear magnetic resonance (NMR) spectra showed broad peaks.
      The NMR and NIR spectra suggested the presence of -OH and -OCH3 functional groups
      in this gum. CONCLUSION: The fractionation improved solubility and facilitated
      further investigations on its characteristics that may have implication on its
      processing, application, and optimization as a potential pharmaceutical
      excipient.

PMID- 23559826
TI  - A validated RP-HPLC method for simultaneous determination of propranolol and
      valsartan in bulk drug and gel formulation.
AB  - OBJECTIVE: A simple, precise, and stability indicating high performance liquid
      chromatography (HPLC) method was developed and validated for the simultaneous
      determination of propranolol hydrochloride and valsartan in pharmaceutical dosage
      form. MATERIALS AND METHODS: The method involves the use of easily available
      inexpensive laboratory reagents. The separation was achieved on Hypersil ODS C-18
      column (250*4.6 mm, i.d., 5 MUm particle size) with isocratic flow with UV
      detector. The mobile phase at a flow rate of 1.0 mL/min consisted of
      acetonitrile, methanol, and 0.01 M disodium hydrogen phosphate (pH 3.5) in the
      ratio of 50:35:15 v/v. RESULTS: A linear response was observed over the
      concentration range 5-50 MUg/mL of propranolol and the concentration range 4-32
      MUg/mL of valsartan. Limit of detection and limit of quantitation for propranolol
      were 0.27 MUg/mL and 0.85 MUg/mL, and for valsartan were 0.45 MUg/mL and 1.39
      MUg/mL, respectively. The method was successfully validated in accordance to ICH
      guidelines acceptance criteria for linearity, accuracy, precision, specificity,
      robustness. CONCLUSION: The analysis concluded that the method was selective for
      simultaneous estimation of propranolol and valsartan can be potentially used for
      the estimation of these drugs in combined dosage form.

PMID- 23559827
TI  - In-silico designing of a potent analogue against HIV-1 Nef protein and protease
      by predicting its interaction network with host cell proteins.
AB  - BACKGROUND: HIV-1 has numerous proteins encoded within its genome, which
      acquaints it with the required arsenal to establish a favorable host cell
      environment suitable for viral replication and pathogenesis. Among these
      proteins, one protein that is indispensable and ambiguous is the Nef protein.
      AIM: Interaction of Nef protein with different host-cell protein was predicted
      and subsequently the down regulation of cluster of differentiation 4 (CD4) was
      targeted through designing of inhibitors of Nef protein for either preventing or
      if not at least delaying pathogenesis. MATERIALS AND METHODS: The interaction
      network of Nef protein with host-cell proteins were predicted by PIMRider.
      Analogue of Lopinavir were prepared and evaluated considering all factors
      affecting the drug stability and toxicity. Finally Docking simulation were
      performed using an Auto-Dock Tool 4.0. RESULTS: In the interaction network of Nef
      protein with different host-cell proteins it was found out that 22 host cell
      proteins are involved in the interaction and execution of different types of
      functions in host cell but these functions are altered with the interaction with
      the Nef protein. After extensive and controlled in silico analysis it has been
      observed that the analogue LOPI1 binds to Nef protein (2NEF) at CD4 interacting
      site residues giving minimum binding energy of -7.68 Kcal/mole, low Ki value of
      2.34 MUM, maximum number of hydrogen bonds (8), good absorption, distribution,
      metabolism and excretion properties, and less toxicity in comparison with the
      standard Lopinavir against HIV1 protease (1HPV). CONCLUSION: The newly designed
      analogue (LOPI1) is showing significant in silico interaction with Nef protein
      and protease and can be taken forward as a potent drug lead, which may finally
      emerge out to be even better than the standard Lopinavir.

PMID- 23559828
TI  - Development and validation of an improved LC-MS/MS method for the quantification
      of desloratadine and its metabolite in human plasma using deutrated desloratadine
      as internal standard.
AB  - PURPOSE: For the determination of desloratadine (DES) and 3-OH desloratadine (3
      OHD) in human plasma using deutrated desloratadine (DESD5) as internal standard
      (IS), a novel stability indicating liquid chromatography-tandem mass
      spectrometric method was developed and validated to support the clinical
      advancement. MATERIALS AND METHODS: The solid-phase extraction method used for
      sample preparation and calibration range was 100-11,000 pg/ml, for which a
      quadratic regression (1/x(2)) was best fitted. The blank plasma was screened and
      observed free from any endogenous interference. RESULTS: The accuracy (% nominal)
      at low limit of quantification LLOQ level for DES and 3-OHD was 100.4% and 99.9%
      whereas precision (%CV) was 4.6 and 5.1%. They (DES and 3-OHD) were stable in
      human plasma after five freeze-thaw cycles, at room temperature for 23.8 hour,
      bench top stability for 6.4 hour. CONCLUSION: This method fulfills all the
      regulatory requirements for selectivity, sensitivity, precision, accuracy,
      stability, goodness of fit, and ruggedness of the method for the determination of
      DES and 3-OHD in human plasma.

PMID- 23559829
TI  - Nipple discharge: An uncommon presentation of a common disease, Tuberculosis.

PMID- 23559830
TI  - Biosimilars: Current regulatory perspective and challenges.

PMID- 23559831
TI  - Semiparametric Regression Pursuit.
AB  - The semiparametric partially linear model allows flexible modeling of covariate
      effects on the response variable in regression. It combines the flexibility of
      nonparametric regression and parsimony of linear regression. The most important
      assumption in the existing methods for the estimation in this model is to assume
      a priori that it is known which covariates have a linear effect and which do not.
      However, in applied work, this is rarely known in advance. We consider the
      problem of estimation in the partially linear models without assuming a priori
      which covariates have linear effects. We propose a semiparametric regression
      pursuit method for identifying the covariates with a linear effect. Our proposed
      method is a penalized regression approach using a group minimax concave penalty.
      Under suitable conditions we show that the proposed approach is model-pursuit
      consistent, meaning that it can correctly determine which covariates have a
      linear effect and which do not with high probability. The performance of the
      proposed method is evaluated using simulation studies, which support our
      theoretical results. A real data example is used to illustrated the application
      of the proposed method.

PMID- 23559832
TI  - Rapid trachoma assessment in Kersa District, Southwest Ethiopia.
AB  - BACKGROUND: Trachoma is the leading cause of infectious blindness worldwide.
      Though trachoma can be treated with antibiotics (active trachoma) or surgery
      (trachomatous trichiasis), it is still endemic in most parts of Ethiopia. Despite
      the prevalence of this infectious disease in different parts of the country,
      district level data is lacking. This study was thus conducted to assess the
      prevalence estimate of trachoma and its risk factors in Kersa District, Southwest
      Ethiopia. METHODS: A community based cross sectional Rapid Assessment of Trachoma
      was conducted using a WHO guideline. Six sub-districts were selected from Kersa
      District based on primary high risk assessment and from each sub-district; 21-27
      households were randomly selected. Active trachoma for children aged 1-9 years,
      trachomatous trichiasis for people above 15 years old and environmental risk
      factors for trachoma were assessed. Data were analyzed using SPSS version 16.
      RESULTS: The overall prevalence estimate of active trachoma was 25.2% (95% CI:
      20.7-30.4%). Forty three percent of children had unclean faces, 11.5% of
      households had water source at more than half hour walking distance, 18.2% did
      not have functional latrine, and 95.3% of the households had solid waste disposal
      within a distance of 20 meters. Households with environmental risk factors were
      at an increased risk to active trachoma, but the association was not
      statistically significant (p>0.05). The prevalence estimate of trachomatous
      trichiasis inclusive of "trachoma suspects" was 4.5%. CONCLUSION: Trachoma is
      endemic in Kersa District with active trachoma being a public health problem in
      the studied sub-districts. Hence, SAFE strategy should be implemented.

PMID- 23559833
TI  - Prevalence of Neisseria gonorrhea and their antimicrobial susceptibility patterns
      among symptomatic women attending gynecology outpatient department in Hawassa
      referral hospital, Hawassa, Ethiopia.
AB  - BACKGROUND: Gonorrhoeae, a sexually transmitted disease caused by Neisseria
      gonorrhea for which humans are the only natural host. The causative organism is
      highly adapted to the genital tract and often causing asymptomatic and undetected
      infection in females in which Acquisition of gonococcal infection late in
      pregnancy can adversely affect labor and delivery as well as the well-being of
      the fetus. The aims of this study were to determine the prevalence and drug
      susceptibility pattern of Neisseria gonorrhea among symptomatic women in Hawassa
      Referral Hospital. METHODS: A cross-sectional study was conducted from December 1
      2010 to February 30, 2011 at Hawassa Referral Hospital. All women who visited
      gynecology outpatient department (OPD) with suspected gonococcal infection were
      included. Endocervical swab was collected by the attending physician. The
      presence of gonorrhea was confirmed by culture, gram staining and biochemical
      tests. Antimicrobial sensitivity test was performed using disc diffusion method
      and the result was interpreted accordingly. RESULTS: Of the total 215 cases
      examined, 11 (5.1%) were confirmed to have gonococcal infection. Although not
      statistically significant, most of the cases 5/11 (45.5%) were in age group of 20
      24 years and the identified organism had low level susceptibility to quinolones
      (ciprofloxacin 55%, ofloxacin 64% & lomefloxacin 64%). CONCLUSION: Despite low
      rates of gonorrhea infection, it is important to focus on high-risk populations
      (reproductive age group) because of the great physical and emotional costs of the
      disease. A high resistance for quinolones, the commonly used antibiotics was
      observed for this laboratory-based diagnosis is recommended.

PMID- 23559834
TI  - The bacteriological safety and antimicrobial susceptibility of bacteria isolated
      from street-vended white lupin (Lupinus albus) in Bahir Dar, Ethiopia.
AB  - BACKGROUND: Whereas street vended foods are readily available sources of meals
      for many people across the world, the microbial safety of such food is always
      uncertain. In developing countries the major sources of food-borne illnesses are
      street vended foods. The aim of this study was thus to assess the prevalence and
      antibiogram of bacteria from white lupin in Bahir Dar Town. METHODS: A total of
      40 samples were processed for detection of indicator bacteria and pathogens from
      December, 2011 to February, 2012 using standard bacteriological techniques.
      Antimicrobial susceptibility test was performed using the Kirby-Bauer disk
      diffusion method. RESULTS: The total coliform counts were 954.2+/-385 and 756.2+/
      447.3 at the surface and the core of white lupin, respectively. On the other
      hand, the fecal coliform counts were 880.9+/-396.6 and 662.1+/-461.9 at surface
      and the core, respectively. There was a statistically significant difference in
      total colifoms and fecal coliform counts between the surface and core of white
      lupin (p <0.05). Escherichia coli 29 (72.5%), Salmonella spp. 23 (57.5%) and
      Shigella spp. 8 (20%) were the pathogens isolated. Most bacterial isolates were
      resistant to tetracycline, cotriamoxazole and erythromycin whereas many of them
      were sensitive to chloramphenicol, nalidixic acid, gentamicin and ciprofloxacin.
      The overall multiple antimicrobial resistances rate was 75%. CONCLUSION: This
      study revealed contamination of white lupin and a potential health to consumers,
      and the bacteria isolated showed high rates of multiple drug resistance.
      Surveillance of antimicrobial resistance should be done on food borne pathogens.
      In addition, further studies should be conducted on the bacteriological quality
      of waters used for soaking white lupin.

PMID- 23559835
TI  - The effects of weathering demonstrated by maternal age on low birth weight
      outcome in babies.
AB  - BACKGROUND: Increasing age has been hypothesized with wear and tear (weathering)
      in mothers, which may result to low birthweight of their babies. The prevalence
      of low birthweight could be heightened if maternal weathering is associated with
      poor maternal socioeconomic variables. In this current study, we analyzed the
      effects of maternal weathering on babies' birthweights. METHODS: One hundred and
      twenty four mother-baby pairs were selected using systematic random sampling
      method. Maternal age formed part of the demographic data that was obtained from
      the mothers' case notes and from interviews held with them. Maternal
      socioeconomic variables were assessed using Oyedeji's parameters and birthweights
      of babies were determined using bassinet weighing scale. Associations between
      maternal socioeconomic variables and birthweight of babies were assessed using
      univariate analysis. Differences in mean birthweight of babies according to their
      maternal age were evaluated using one-way analysis of variance ANOVA. RESULTS:
      Among the 124 babies, 66(53.2%) were males and 58(46.8%) females of whom the
      majority 104(83.9%, had normal birthweight. The mean birthweight of babies was
      3.05+/-0.57 (95% CI, 2.95-3.15) kg, while the mean maternal age was 23.60 (5.2)
      95% CI, (22.68-24.52) years. The difference between mean birthweight of babies
      and mean maternal age was not significant (F=1.35, p=0.255). Similarly, the
      association between birthweight, maternal education and occupation computed using
      univariate analysis was not significant (F=2.163, p=0.120) for education and
      (F=1.825, p=0.166) for occupation. CONCLUSION: In this study, maternal weathering
      was not found to be associated with LBW outcome. This implies that an increase in
      maternal age may not be significantly associated with LBW. However, there is need
      for further research on this subject from different centers using larger sample
      size in order to enhance the precision of the study.

PMID- 23559836
TI  - Psychopathological correlates of child sexual abuse: the case of female students
      in Jimma zone, South West Ethiopia.
AB  - BACKGROUND: Arguably, the sexual abuse of children raises a number of important
      questions for researchers at different times. Thus, the present study was aimed
      to examine psychopathological correlates of child sexual abuse. METHODS: This
      cross-sectional survey study compared the degree of vulnerability to
      psychopathological variables among respondents with a history of sexual abuse and
      their unabused counter parts in Jimma Zone. To this end, 400 female students were
      selected from five high schools as the sample population using multi-stage
      sampling procedure. Data were gathered using Reynold's Adolescent Depression
      Scale (RADS), Adolescent Panic Anxiety Scale, and Posttraumatic stress disorder
      test. The collected data via self-administered questionnaire were analyzed
      through the two sample t-test statistical procedure. RESULTS: The study revealed
      a result of t=3.83 for depression, t=2.46 for panic episode, and t=4.23 for PTSD
      score, whereas, the critical value of all the three psychopathological variables
      showed t (52) =1.676 at P=0.05. Results illustrate the presence of statistically
      significant differences in the mean scores of the above mentioned
      psychopathologies between females with history of sexual abuse and females who
      were not victims of this sexual attack at df =52 and P=0.05. CONCLUSION: The
      findings of the present study indicate that history of childhood sexual abuse has
      adverse consequences on the future psychological wellbeing of females.
      Specifically, females with experience of sexual abuse were found to be more
      susceptible to develop depression, panic anxiety, and post-traumatic stress
      disorders than unabused females. Thus, parents, and teachers should give the
      necessary care and protection to female children. Primary bio-psychosocial care
      services need to be established in the school system, and both the Ministry of
      Health and the Ministry of Education should work together against sexual
      exploitation of female children.

PMID- 23559837
TI  - Prevalence and assessment of factors contributing to adverse drug reactions in
      wards of a tertiary care hospital, India.
AB  - BACKGROUND: Adverse drug reactions account for the highest proportion among the
      causes of morbidity and mortality in clinical wards and are posing a considerable
      challenge. Hence, the objective of this study was to find out the prevalence of
      adverse drug reactions and the factors which contribute to their prevalence.
      METHODS: A prospective patient record review was carried out at a tertiary care
      hospital in North India from August 2010-May 2011. A total of 1033 subjects
      admitted to hospital for any kind of treatment were included while patients
      admitted in the ward because of adverse drug reactions were excluded. The ward
      where we collected the data includes multispecialty and cardiovascular wards. The
      causality, severity, and preventability of adverse drug reactions were assessed
      using Naranjo, modified Hartwig, and Schumock and Thornton criteria,
      respectively. Kolmogorov-Smyrnov, chi -square and multiple logistic regression
      tests were used to determine adverse drug reactions ascribed to drugs. RESULTS:
      Out of 1033 patients whose records were assessed, 167(16.2%) experienced one or
      more adverse drug reactions. The metabolic systems, which accounted for 49(24.6%)
      were most frequently affected by adverse drug reactions, followed by
      gastrointestinal, 45(22.6%); hematological, 28(14.1%) and cutaneous, 21(10.6%)
      systems. The drug classes most frequently associated with the reactions were
      antibiotics 40(20.1%), diuretics 35(17.6%) and anticoagulants 30(15.1%).
      According to the selected preventability scale, 72(36.2%) adverse drug reactions
      were classified as probably or definitely preventable. About 165(83%) of the
      reactions were type A, which represents augmentation of the pharmacological
      action of a drug. Number of drugs, length of hospitalization and number of
      diagnosis were identified as significant predisposing factors for ADRs.
      CONCLUSION: The result of this study suggested that adverse drug reactions were
      significant causes of superimposed health problems that occur following
      hospitalization. The major risk factors associated with ADR include number of
      drugs, length of hospitalization and number of diagnosis. Based on the findings a
      rigorous study is recommended to determine the burden and identify the risk
      factors of adverse drug reactions to target interventions.

PMID- 23559838
TI  - Relationship between leadership styles of nurse managers and nurses' job
      satisfaction in Jimma University Specialized Hospital.
AB  - BACKGROUND: Leadership style of nurse managers plays a significant role in
      nurses' job satisfaction. However, there is limited literature in areas related
      to nurses' manager leadership style. The objective of this research was thus to
      investigate the relationship between leadership style of nurse managers and
      nurses' job satisfaction in Jimma University Specialized Hospital. METHODS: The
      study was conducted at Jimma University Specialized Hospital from January to June
      2012 and used a non-experimental correlation design. All full time, non
      supervisory nurses with an experience of more than one year in nursing profession
      were participated in the study. The Multifactor Leadership Questionnaire and
      Minnesota Satisfaction Questionnaire were used to collect data. Data were entered
      and analyzed using SPSS version16.0 statistical software. The results were
      analyzed through descriptive statistics followed by the application of
      inferential statistics on the variables. Significance level was considered when
      p<0.05. RESULTS: A total of 175 copies of the questionnaires were returned out of
      186 copies distributed to respondents. The result indicated that nurses can
      prefer transformational leadership style over transactional leadership style and
      had moderate-level intrinsic (M=2.72, SD=0.71) but low level of extrinsic job
      satisfaction (M=1.83, SD=0.68). Furthermore, from transactional leadership, only
      contingent reward was found to be statically significant and correlated with
      extrinsic (B=0.45, p<0.01) and intrinsic job satisfaction (B=0.32, p<0.05) while
      all five dimension of transformational leadership style were statistically
      significant and correlated with both intrinsic and extrinsic job satisfaction.
      CONCLUSION: Nurses tended to be more satisfied with the transformational
      leadership than transactional leadership style. Therefore, nurses' managers
      should use transformational leadership style in order to increase nurses' job
      satisfaction.

PMID- 23559839
TI  - Effect of aerobic exercise training on maternal weight gain in pregnancy: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Weight gains in pregnancy within the recommended guidelines are
      associated with healthy fetal and maternal outcomes; higher weight gains are
      associated with fetal macrosomia. This study was a systemic review of randomized
      controlled trials on the effect of aerobic training on maternal weight in
      pregnancy. METHODS: The study data source was publications through May 2012 in
      the MEDLINE (PubMed) database. The citation lists of randomized controlled trials
      on the effect of aerobic training and maternal weight were extracted. Data on
      participants' characteristics, study quality, population, intervention, treatment
      outcome (maternal weight gain) were collected and analyzed. RESULTS: There were
      11 randomized controlled studies using body weight (kg) as measure of treatment
      outcome. A total of 1177 subjects were recruited in the 11 studies. The mean+/-
      SD weight gain (kg) for the exercise (11.31+/- 7.44kg) and control (14.42+/-
      6.60kg) groups; Meta-analysis result indicated significant effect of aerobic
      training on maternal weight (t= -7.580, p= .000) at p< 0.05. CONCLUSION: It was
      concluded that aerobic training is an effective tool in maternal weight gain
      control in pregnancy. More randomized controlled trials are warranted.

PMID- 23559840
TI  - Leech infestation: the unusual cause of upper airway obstruction.
AB  - This paper presents a case of a 7 year-old child who presented with a 14-days
      history of blood stained saliva and shortness of breath of 3 days with signs of
      upper airway obstruction. Laryngoscopy revealed a blackish living foreign body in
      the proximal trachea. Under general anesthesia the leech was removed by applying
      forceps. I conclude that a high index of suspicion of leech infestation is
      required when faced with a child presenting with unexplained bleeding per mouth
      and signs of upper airway obstruction.

PMID- 23559841
TI  - Endometriosis of the appendix presenting as acute appendicitis: a case report and
      literature review.
AB  - Endometriosis is a common disease generally, but appendiceal endometriosis
      causing acute appendicitis is a very uncommon clinical phenomenon and a few cases
      have been reported. The authors aim to highlight the rarity of such clinical
      entity in Nigeria. A 29 year old nulliparous woman presented with severe right
      iliac fossa pains, tenderness and rebound tenderness on her second day of
      menstruation. She subsequently had appendicectomy and a histopathological
      diagnosis of appendiceal endometriosis causing acute appendicitis. Appendiceal
      endometriosis causing acute appendicitis is rare, and definitive diagnosis is
      performed through histopathological evaluation. Post-operative gynaecological
      follow-up is highly recommended.

PMID- 23559842
TI  - Prodromal herpes zoster mimicking odontalgia--a diagnostic challenge.
AB  - Herpes zoster (shingles) is caused by reactivation of the latent varicella zoster
      virus which is present due to an earlier varicella infection (chicken-pox).
      Herpes Zoster is a less common and endemic disease than varicella, although
      factors causing reactivation are still not well known, but it occurs in older
      and/or immunocompromised individuals. Involvement of C3, T5, L1, L2 and first
      division of trigeminal nerve are the most frequently encountered whereas the
      involvement of second and third division of trigeminal nerve is rarely seen.
      During the prodromal stage, the only presenting symptom may be odontalgia, which
      may prove to be a diagnostic challenge for the dentist, since many diseases can
      cause orofacial pain, and the diagnosis must be properly established before final
      treatment. Here we present a case of herpes zoster involving the second division
      of trigeminal nerve masquerading as odontalgia. The difficulties in diagnosis and
      management are discussed.

PMID- 23559843
TI  - The need for initiation of school health program in Ethiopia.

PMID- 23559844
TI  - Linking Life Skills and Norms With Adolescent Substance Use and Delinquency in
      South Africa.
AB  - We examined factors targeted in two popular prevention approaches with adolescent
      drug use and delinquency in South Africa. We hypothesized adolescent life skills
      to be inversely related, and perceived norms to be directly related to later drug
      use and delinquency. Multiple regression and a relative weights approach were
      conducted for each outcome using a sample of 714 South African adolescents ages
      15 to 19 years (M = 15.8 years, 57% female). Perceived norms predicted gateway
      drug use. Conflict resolution skills (inversely) and perceived peer acceptability
      (directly) predicted harder drug use and delinquency. The "culture of violence"
      within some South African schools may make conflict resolution skills more
      salient for preventing harder drug use and delinquency.

PMID- 23559845
TI  - Risky Behavior in Affluent Youth: Examining the Co-occurrence and Consequences of
      Multiple Problem Behaviors.
AB  - Children of affluent parents are often excluded in psychological research as they
      are considered to be at "low risk"; however, research is beginning to suggest
      that this previously under-studied population may be at risk for developing
      multiple problem behaviors, including substance use and externalizing problems.
      The current study aimed to extend the application of Problem Behavior Theory
      (PBT) to a sample of affluent adolescents by examining the extent to which these
      behaviors co-occurred and were associated with negative outcomes. Data were
      collected from 1,147 high school students living in an affluent community via
      anonymous questionnaires regarding their engagement in various problem behaviors.
      PBT was supported in this sample, and youth who engaged in multiple problem
      behaviors reported experiencing more negative outcomes than youth who did not
      engage in these behaviors. The findings of this study support the
      generalizability of PBT and also highlight the importance of continuing to study
      affluent youth in addition to traditionally high-risk populations.

PMID- 23559846
TI  - Sexual Hookup Culture: A Review.
AB  - "Hookups," or uncommitted sexual encounters, are becoming progressively more
      engrained in popular culture, reflecting both evolved sexual predilections and
      changing social and sexual scripts. Hook-up activities may include a wide range
      of sexual behaviors, such as kissing, oral sex, and penetrative intercourse.
      However, these encounters often transpire without any promise of, or desire for,
      a more traditional romantic relationship. A review of the literature suggests
      that these encounters are becoming increasingly normative among adolescents and
      young adults in North America, representing a marked shift in openness and
      acceptance of uncommitted sex. We reviewed the current literature on sexual
      hookups and considered the multiple forces influencing hookup culture, using
      examples from popular culture to place hooking up in context. We argue that
      contemporary hookup culture is best understood as the convergence of evolutionary
      and social forces during the developmental period of emerging adulthood. We
      suggest that researchers must consider both evolutionary mechanisms and social
      processes, and be considerate of the contemporary popular cultural climate in
      which hookups occur, in order to provide a comprehensive and synergistic
      biopsychosocial view of "casual sex" among emerging adults today.

PMID- 23559847
TI  - Roles of tumor necrosis factor alpha gene polymorphisms, tumor necrosis factor
      alpha level in aqueous humor, and the risks of open angle glaucoma: a meta
      analysis.
AB  - PURPOSE: This meta-analysis was performed to clarify the association between
      tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and open angle
      glaucoma (OAG) risks, and the association between the TNF-alpha level in aqueous
      humor (AH) and the risks of glaucoma. METHODS: A computerized literature search
      was performed for the relevant available studies from three databases including
      PubMed, ISI Web of Science, and Embase. The fixed or random effect model was
      selected based on the heterogeneity test using the Q test and the I(2) statistic.
      The associations between TNF-alpha gene polymorphisms and OAG risks were
      estimated by calculating pooled odds ratios (ORs) and the 95% confidence interval
      (CI), while a pooled standardized mean difference with 95% CI was used for the
      comparison of TNF-alpha levels in AH between patients with OAG and controls.
      Publication bias was estimated using Begg's funnel plots and Egger's regression
      test. RESULTS: A total of 14 (1,182 cases and 3,003 controls), five (808 cases
      and 1,039 controls), three (645 cases and 666 controls), and three studies (404
      cases and 625 controls) were finally included in the analyses for the
      associations between TNF-alpha -308G/A, -857C/T, -863C/A, and -238G/A
      polymorphisms and the risks of OAG, respectively. The combined results showed
      that the TNF-alpha -308G/A gene polymorphism was significantly associated with
      risks of high-tension glaucoma (A versus G: OR=1.660, 95% CI=1.033-2.667; AA/AG
      versus GG: OR=1.713, 95% CI=1.10-2.651), but not with normal tension glaucoma or
      exfoliation glaucoma. Ethnicity-stratified analysis revealed that a significant
      association also existed in Asians (A versus G: OR=1.947, 95% CI=1.097-3.456;
      AA/AG versus GG: OR=1.949, 95% CI=1.140-3.332). None of the other polymorphisms
      was significantly associated with OAG risks. Furthermore, the pooled results of
      six studies showed that the TNF-alpha levels in the AH of patients with OAG was
      higher than that of the control subjects (standardized mean difference=0.517, 95%
      CI=0.207-0.826, p=0.001). Probability of publication bias was low across all
      comparisons illustrated by the funnel plots and Egger's test. CONCLUSIONS: This
      meta-analysis suggests that patients with OAG may have higher TNF-alpha levels
      compared with the control subjects, and the TNF-alpha -308G/A polymorphism is
      significantly associated with the risks of high-tension glaucoma. Since potential
      confounders could not be ruled out completely, further studies are needed to
      confirm these results.

PMID- 23559848
TI  - Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal
      neovascularization.
AB  - PURPOSE: To investigate the applicability of serine/arginine-rich protein kinase
      (SRPK)-specific inhibitor, SRPIN340, for attenuation of choroidal
      neovascularization (CNV) formation using a mouse model. METHODS: Laser
      photocoagulation was performed to induce CNV in C57BL/6J mice, followed by
      intravitreal injection of SRPIN340 or vehicle. Seven days after the treatment,
      the CNV size was evaluated using a flatmount technique. Protein levels of
      vascular endothelial growth factor (VEGF) and inflammation-associated molecules,
      such as monocyte chemoattractant protein (MCP)-1 and intercellular adhesion
      molecule (ICAM)-1, in the retinal pigment epithelium-choroid complex were
      measured with enzyme-linked immunosorbent assay. Expression levels of total Vegf,
      exon 8a-containing Vegf isoforms, and F4/80 (a specific marker for macrophage)
      were assessed using real-time PCR. RESULTS: SRPIN340 inhibited CNV formation in a
      dose-dependent manner. Compared with the vehicle, SRPIN340 significantly
      decreased the protein levels of VEGF, MCP-1, ICAM-1, and consequently inhibited
      macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression
      levels of total Vegf and exon 8a-containing Vegf isoforms. CONCLUSIONS: SRPIN340,
      a specific inhibitor of SRPK, suppressed Vegf expression and attenuated CNV
      formation. Our data suggest the possibility that SRPIN340 is applicable for
      neovascular age-related macular degeneration as a novel chemical therapeutics.

PMID- 23559850
TI  - Role of B lymphoma Mo-MLV insertion region 1 in the oncogenic behavior of
      retinoblastomas.
AB  - PURPOSE: This study investigated the relationship between B lymphoma Mo-MLV
      insertion region 1 (BMI-1)--a polycomb protein for stem cell self-renewal and
      proliferation--and the clinicopathological parameters of human retinoblastomas,
      including differentiation status and retinal tissue invasion, as well as the
      effects of BMI-1 on retinoblastoma Y79 cells. METHODS: Thirty-four archived human
      retinoblastoma samples were recruited for BMI-1 immunohistochemistry. The
      percentage of BMI-1-expressing cells was scored by independent pathologists and
      the data were correlated with the clinical features. Y79 cells were transfected
      to overexpress or specifically inhibit BMI-1 for cell proliferation, propidium
      iodide cell cycle and terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) apoptosis analyses, multicellular sphere formation assay, and
      gene expression study. RESULTS: BMI-1 was widely expressed in human
      retinoblastomas. Higher percentages of BMI-1-expressing cells were selectively
      limited to undifferentiated tumors and those tumors undergoing invasion to the
      optic nerve and choroid. However, there was no difference in BMI-1 expression in
      retinoblastoma retinas with or without tumor invasion. In Y79 cells, BMI-1
      stimulated cell proliferation and suppressed apoptosis with reduced p14ARF and
      p16INK4 expression, along with upregulation of proliferating cell nuclear
      antigens cyclin D1 and D2. In contrast, silencing BMI-1 reversed these changes.
      It also upregulated CHX10 and Rx, but not other retinal development-related
      genes, including nestin and neurofilament M. CONCLUSIONS: Our work indicates that
      BMI-1 might render important oncogenic property of retinoblastomas and it could
      be a therapeutic target for the cancer treatment.

PMID- 23559849
TI  - Global microRNA expression profiling: curcumin (diferuloylmethane) alters
      oxidative stress-responsive microRNAs in human ARPE-19 cells.
AB  - PURPOSE: In recent years, microRNAs (miRNAs) have been reported to play important
      roles in a broad range of biologic processes, including oxidative stress-mediated
      ocular diseases. In addition, the polyphenolic compound curcumin has been shown
      to possess anti-inflammatory, antioxidant, anticancer, antiproliferative, and
      proapoptotic activities. The aim of this study was to investigate the impact of
      curcumin on the expression profiles of miRNAs in ARPE-19 cells exposed to
      oxidative stress. METHODS: MiRNA expression profiles were measured in ARPE-19
      cells treated with 20 MUMU curcumin and 200 MUMU H2O2. PCR array analysis was
      performed using web-based software from SABiosciences. The cytotoxicity of ARPE
      19 cells was determined with the CellTiter-Blue cell viability assay. The effects
      of curcumin on potential miRNA targets were analyzed with quantitative real-time
      PCR and western blotting. RESULTS: Curcumin treatment alone for 6 h had no effect
      on ARPE-19 cell viability. Incubation with H2O2 (200 uM) alone for 18 h decreased
      cell viability by 12.5%. Curcumin alone downregulated 20 miRNAs and upregulated
      nine miRNAs compared with controls. H2O2 downregulated 18 miRNAs and upregulated
      29 miRNAs. Furthermore, curcumin pretreatment in cells exposed to H2O2
      significantly reduced the H2O2-induced expression of 17 miRNAs. As determined
      with quantitative real-time PCR and western blotting, curcumin increased the
      expression of antioxidant genes and reduced angiotensin II type 1 receptor,
      nuclear factor-kappa B, and vascular endothelial growth factor expression at the
      messenger RNA and protein levels. CONCLUSIONS: The results demonstrated that
      curcumin alters the expression of H2O2-modulated miRNAs that are putative
      regulators of antioxidant defense and renin-angiotensin systems, which have been
      reported to be linked to ocular diseases.

PMID- 23559851
TI  - Exclusion of pathogenic promoter region variants and identification of novel
      nonsense mutations in the zinc finger E-box binding homeobox 1 gene in posterior
      polymorphous corneal dystrophy.
AB  - PURPOSE: To report the identification of five novel nonsense mutations in the
      zinc finger E-box binding homeobox 1 (ZEB1) gene and exclusion of promoter region
      mutations in individuals without ZEB1 coding region mutations in posterior
      polymorphous corneal dystrophy (PPCD). METHODS: Slit-lamp examination and DNA
      collection were performed for individuals diagnosed with PPCD and, when
      available, affected and unaffected family members. Genomic DNA prepared from
      peripheral blood leukocytes and buccal epithelial cells underwent PCR
      amplification and automated sequencing of the ZEB1 gene and 1 kb 5' of ZEB1,
      presumably containing the ZEB1 promoter region. RESULTS: Thirteen unrelated
      individuals with PPCD were identified, and genomic DNA was collected from each
      individual. ZEB1 mutations were identified in six of the 13 probands, five of
      which were novel: p.(Gly150Alafs*36; spontaneous), p.(His230Argfs*7),
      p.(Ser638Cysfs*5), p.(Glu1039Glyfs*6), and p.(Gln884Argfs*37). Screening of the
      ZEB1 promoter region in 31 probands with PPCD without a ZEB1 coding region
      mutation identified only two known single nucleotide polymorphisms (SNPs) whose
      frequency in the affected probands did not differ significantly from that in the
      general population. CONCLUSIONS: We report five novel frame-shift mutations, one
      confirmed as spontaneous, in the ZEB1 gene associated with PPCD, bringing the
      total number of reported pathogenic mutations to 24, and the percentage of PPCD
      associated with ZEB1 mutations to 32%. The absence of ZEB1 promoter region
      mutations in probands without a ZEB1 coding region mutation indicates that other
      genetic loci, such as the PPCD1 locus, are involved in the pathogenesis of PPCD.

PMID- 23559852
TI  - High-resolution matrix-assisted laser desorption ionization-imaging mass
      spectrometry of lipids in rodent optic nerve tissue.
AB  - PURPOSE: To develop a method for generating high spatial resolution (10 um)
      matrix-assisted laser desorption ionization (MALDI) images of lipids in rodent
      optic nerve tissue. METHODS: Ice-embedded optic nerve tissue from rats and mice
      were cryosectioned across the coronal and sagittal axes of the nerve fiber.
      Sections were thaw mounted on gold-coated MALDI plates and were washed with
      ammonium acetate to remove biologic salts before being coated in 2,5
      dihydroxybenzoic acid by sublimation. MALDI images were generated in positive and
      negative ion modes at 10 um spatial resolution. Lipid identification was
      performed with a high mass resolution Fourier transform ion cyclotron resonance
      mass spectrometer. RESULTS: Several lipid species were observed with high signal
      intensity in MALDI images of optic nerve tissue. Several lipids were localized to
      specific structures including in the meninges surrounding the optic nerve and in
      the central neuronal tissue. Specifically, phosphatidylcholine species were
      observed throughout the nerve tissue in positive ion mode while sulfatide species
      were observed in high abundance in the meninges surrounding the optic nerve in
      negative ion mode. Accurate mass measurements and fragmentation using sustained
      off-resonance irradiation with a high mass resolution Fourier transform ion
      cyclotron resonance mass spectrometer instrument allowed for identification of
      lipid species present in the small structure of the optic nerve directly from
      tissue sections. CONCLUSIONS: An optimized sample preparation method provides
      excellent sensitivity for lipid species present within optic nerve tissue. This
      allowed the laser spot size and fluence to be reduced to obtain a high spatial
      resolution of 10 um. This new imaging modality can now be applied to determine
      spatial and molecular changes in optic nerve tissue with disease.

PMID- 23559853
TI  - Altered protein conformation and lower stability of the dystrophic transforming
      growth factor beta-induced protein mutants.
AB  - PURPOSE: Transforming growth factor beta-induced protein (TGFBIp) is a widely
      expressed extracellular matrix protein that plays roles in cell adhesion and
      migration, differentiation, apoptosis, bone morphogenesis, and carcinogenesis.
      Mutations of TGFBIp have been linked to stromal corneal dystrophies, a group of
      protein conformational diseases characterized by abnormal protein aggregations in
      the cornea. However, the underlying pathogenic mechanism remains elusive due to a
      lack of insight into the molecular properties of the disease-causing mutants. In
      the current study, we applied spectroscopic tools to compare the conformation and
      protein stability of recombinant wild-type (WT) TGFBIp to two dystrophic mutants,
      R124C and R555W. METHODS: A serum-free expression system was used to produce the
      recombinant TGFBIp proteins. Fluorescence and far-ultraviolet circular dichroism
      spectroscopies were used to compare WT and dystrophic mutants under various
      conditions. RESULTS: Our results showed that dystrophic mutants were processed
      differentially by the expressing cells and produced different proteolytic
      fragment patterns by proteolysis. Intrinsic tryptophan fluorescence studies
      revealed moderate shifts in the emission maxima and increased quenching by iodide
      ion of mutant TGFBIp, suggesting a different conformation than WT protein.
      Denaturation experiments indicated a difference in protein stability between WT
      and mutant proteins. Under oxidizing conditions, the mutants produced higher 1
      anilinonaphthalene-8-sulfonic acid and thioflavin T fluorescence signals than the
      WT, indicating increased protein unfolding and fibril formation, respectively.
      Finally, far-ultraviolet circular dichroism spectroscopy revealed that WT TGFBIp
      undergoes concentration-dependent conformational changes; similar experiments
      were not possible on mutant TGFBIp, which remained soluble only at low
      concentrations. CONCLUSIONS: Our study provides new evidence for the pathogenic
      mechanism of dystrophic mutants. Although mutant TGFBIp has moderate but
      consistent structural perturbations, other factors such as oxidation or
      degradation may be required to cause the phenotypic abnormal aggregations.

PMID- 23559854
TI  - Increased importin 13 activity is associated with the pathogenesis of pterygium.
AB  - PURPOSE: We previously reported that importin 13 (IPO13), a member of the
      importin-beta family of nuclear import proteins, regulates nuclear import of the
      glucocorticoid receptor in airway epithelial cells, IPO13 serves as a potential
      marker for corneal epithelial progenitor cells, and IPO13 is associated with
      corneal cell proliferation. Here we investigated the role of IPO13 in the
      pathogenesis of pterygium and the underlying mechanism including interaction with
      other cell proliferation-related factors: keratin 17 (K17), a lesional protein
      and a member of the type I keratins, and c-Jun, a protein of the activator
      protein-1 complex. METHODS: Tissue samples were collected from primary pterygia,
      recurrent pterygia, and normal conjunctiva to perform the following experiments:
      immunohistochemical measurement of IPO13 and K17. Pterygium epithelial cells
      (PECs) were cultured in keratinocyte serum-free defined medium to examine the
      expression of IPO13 and K17. Lentivirus-mediated silencing and overexpression
      IPO13 testing was conducted, and K17 alternation was evaluated with western blot
      and immunostaining. In addition, the translocation of c-Jun (a K17 regulator) was
      further examined after IPO13 was silenced. RESULTS: IPO13 activity was
      significantly increased in the basal layer of the epithelium of the pterygium. In
      cultured PECs, overexpression or knockdown of the IPO13 gene increased or
      decreased PEC proliferation, respectively. IPO13 was colocalized with K17 in the
      epithelium of the pterygium, and overexpression or knockdown of the IPO13 gene
      induced upregulation or downregulation of K17 expression in PECs, respectively.
      In addition, silencing of the IPO13 gene blocked nuclear translocation of c-Jun.
      CONCLUSIONS: We provided novel evidence that IPO13 may contribute to the
      pathogenesis of pterygium via modulation of K17 and c-Jun.

PMID- 23559855
TI  - Porcine corneal cell culture models for studying epidemic keratoconjunctivitis.
AB  - PURPOSE: Epidemic keratoconjunctivitis (EKC) is a severe ocular infection caused
      by a few types (8, 19a [relabeled as 64 recently], 37, 53, and 54) of human
      adenoviruses (HAdVs). HAdVs are known for their strong host species specificity
      that limits studying HAdV virulence and pathophysiology in animal models.
      METHODS: A HAdV infection model of primary porcine corneal epithelial cells
      (PPCE) and primary porcine corneal keratocytes (PPCK) was established and
      compared to primary human corneal epithelial cells (PHCE) and primary human
      corneal keratocytes (PHCK). Induction of interleukin-8 (IL-8) messenger RNA
      (mRNA), HAdV DNA replication, and the release of infectious virus progeny by the
      EKC-associated type HAdV-D37 and the non-EKC-associated type HAdV-D22 were
      studied. RESULTS: PPCE and PPCK morphology and the expression of alpha2,3-linked
      sialic acid, the main receptor of EKC-associated HAdV types, were akin to human
      corneal cells (PHCE and PHCK). Induction of IL-8 mRNA was observed as early as 8
      h after HAdV infection. Induction of IL-8 mRNA by HAdV-D37 infection was
      significantly higher (p<=0.001) than by HAdV-D22 infection in PPCE, PPCK, PHCE,
      and PHCK. Detection of HAdV-DNA replication, release of infectious virus progeny,
      and the development of cytopathic effect indicated that PPCE and PPCK were fully
      permissive for HAdV-D37 and HAdV-D22 replication as were the human corneal cells
      (PHCE and PHCK). Infectious virus titers after HAdV-D37 infection (1.0 * 10(5)
      TCID50/ml) were significantly higher (p=0.001) than after HAdV-D22 infection (1.8
      * 10(4) TCID50/ml) in PPCE, PHCE, and PHCK but not significantly different in
      PPCK. CONCLUSIONS: Primary porcine epithelial cells and keratocytes are nonhuman
      corneal cell culture models fully permissive for HAdV infection. The models hold
      promise for studying the virulence and pathophysiology of EKC-associated
      adenovirus types compared to other adenovirus types.

PMID- 23559856
TI  - Comparative proteomics analysis of degenerative eye lenses of nocturnal rice eel
      and catfish as compared to diurnal zebrafish.
AB  - PURPOSE: The aim of this study was to determine the lens crystallin diversity of
      degenerative eyes from the rice eel (Monopterus albus) and walking catfish
      (Clarias batrachus) as compared to that of zebrafish (Danio rerio) by using
      comparative proteomics methodologies. We endeavored to investigate the evolution
      of vertebrate lenses particularly concerning the functional loss of lenses in
      degenerative eyes of rice eels and catfishes living under an environment of
      perpetual darkness. METHODS: Fish lenses were collected and homogenized to
      extract total soluble proteins. The protein mixtures were separated by one- and
      two-dimensional gel electrophoresis (1D or 2D gel), plus the newer gel-free
      shotgun proteomic strategy, followed by in-gel digestion and subjection of the
      digested protein bands or spots to liquid chromatography coupled with tandem mass
      spectrometry. The proteomics data were analyzed and compared based on the
      proteomics databank of zebrafish. The soluble lens protein solutions of three
      piscine species were also processed by gel-filtration chromatography and 1D
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the comparison and
      validation of various crystallin families, e.g., alpha-, beta-, and gamma
      crystallins. RESULTS: In zebrafish eye lenses, gamma-crystallin constituted about
      71% and alpha- and beta-crystallins comprised 30% of total lens proteins. In rice
      eel lenses, very little or almost no alpha-crystallins were detected and beta-
      and gamma-crystallins comprised more than 98% of total lens proteins. In catfish
      lenses, alpha- and beta-crystallins comprised about 40% and gamma-crystallin
      constitutes 60% of total lens proteins. It was of interest to find that alpha
      crystallin was totally absent in the rice eel in contrast to the presence, albeit
      with very low amounts, of alpha-crystallin in similarly nocturnal catfish. The
      ratio of alpha-crystallin subunits (alphaA/alphaB) was found to be about 20:1 for
      the catfish lens, in great contrast to the ratio of about 3:1 found for most
      mammalian lenses. In contrast, beta- and gamma-crystallins were more abundant in
      lenses of these three piscine species, similar to mammalian lenses. By proteomics
      analysis, the most abundant beta-crystallins were found to comprise a diverse
      group of betaA1a, betaA1-2, betaA2a, betaA2-2, betaA4, betaB1, betaB2, and betaB3
      subunit crystallins; the monomeric gamma-crystallin class contains gammaB,
      gammaD, gammaM2, gammaM3, gammaM5, gammaM7, gammaN-A, gammaN-B, gammaS1, and
      gammaS2 crystallins. CONCLUSIONS: In cave or nocturnal animals, the eye is
      sometimes reduced or eliminated because of adaptation to life in visual darkness.
      The comparative proteomics analysis of degenerative and normal lenses forms a
      firm molecular basis to investigate further the evolution of piscine lenses in
      the future. The total numbers of alpha-, beta-, and gamma-crystallins in the
      three fish species as revealed by the current proteomics methodology clearly
      indicate the complexity and diversity of crystallin species present in the
      piscine class of vertebrates. The unexpected finding that alpha-crystallin is
      absent in the degenerative eye lenses of rice eel may have some bearing on the
      chaperone function of alpha-crystallin in regard to its protective role of
      preventing protein aggregation in diurnal vertebrate lenses to maintain
      functional transparency.

PMID- 23559857
TI  - Lack of association between the protein tyrosine phosphatase non-receptor type 22
      R263Q and R620W functional genetic variants and endogenous non-anterior uveitis.
AB  - OBJECTIVE: Endogenous uveitis is a major cause of visual loss mediated by the
      immune system. The protein tyrosine phosphatase non-receptor type 22 (PTPN22)
      gene encodes a lymphoid-specific phosphatase that plays a key role in T-cell
      receptor (TCR) signaling. Two independent functional missense single nucleotide
      polymorphisms (SNPs) located within the PTPN22 gene (R263Q and R620W) have been
      associated with different autoimmune disorders. We aimed to analyze for the first
      time the influence of these PTPN22 genetic variants on endogenous non-anterior
      uveitis susceptibility. METHODS: We performed a case-control study of 217
      patients with endogenous non-anterior uveitis and 718 healthy controls from a
      Spanish population. The PTPN22 polymorphisms (rs33996649 and rs2476601) were
      genotyped using TaqMan allelic discrimination assays. The allele, genotype,
      carriers, and allelic combination frequencies were compared between cases and
      controls with chi(2) analysis or Fisher's exact test. RESULTS: Our results showed
      no influence of the studied SNPs in the global susceptibility analysis
      (rs33996649: allelic P- value=0.92, odds ratio=0.97, 95% confidence interval=0.54
      1.75; rs2476601: allelic P- value=0.86, odds ratio=1.04, 95% confidence
      interval=0.68-1.59). Similarly, the allelic combination analysis did not provide
      additional information. CONCLUSIONS: Our results suggest that the studied
      polymorphisms of the PTPN22 gene do not play an important role in the
      pathophysiology of endogenous non-anterior uveitis.

PMID- 23559859
TI  - Detection of novel mutations that cause autosomal dominant retinitis pigmentosa
      in candidate genes by long-range PCR amplification and next-generation
      sequencing.
AB  - PURPOSE: To devise an effective method for detecting mutations in 12 genes (CA4,
      CRX, IMPDH1, NR2E3, RP9, PRPF3, PRPF8, PRPF31, PRPH2, RHO, RP1, and TOPORS)
      commonly associated with autosomal dominant retinitis pigmentosa (adRP) that
      account for more than 95% of known mutations. METHODS: We used long-range PCR (LR
      PCR) amplification and next-generation sequencing (NGS) performed in a GS Junior
      454 benchtop sequencing platform. Twenty LR-PCR fragments, between 3,000 and
      10,000 bp, containing all coding exons and flanking regions of the 12 genes, were
      obtained from DNA samples of patients with adRP. Sequencing libraries were
      prepared with an enzymatic (Fragmentase technology) method. RESULTS: Complete
      coverage of the coding and flanking sequences of the 12 genes assayed was
      obtained with NGS, with an average sequence depth of 380* (ranging from 128* to
      1,077*). Five previous known mutations in the adRP genes were detected with a
      sequence variation percentage between 35% and 65%. We also performed a parallel
      sequence analysis of four samples, three of them new patients with index adRP, in
      which two novel mutations were detected in RHO (p.Asn73del) and PRPF31
      (p.Ile109del). CONCLUSIONS: The results demonstrate that genomic LR-PCR
      amplification together with NGS is an effective method for analyzing individual
      patient samples for mutations in a monogenic heterogeneous disease such as adRP.
      This approach proved effective for the parallel analysis of adRP and has been
      introduced as routine. Additionally, this approach could be extended to other
      heterogeneous genetic diseases.

PMID- 23559858
TI  - Exome sequencing identifies a novel and a recurrent BBS1 mutation in Pakistani
      families with Bardet-Biedl syndrome.
AB  - PURPOSE: To determine the genetic cause of Bardet-Biedl syndrome (BBS) in two
      consanguineous Pakistani families. METHODS: Clinical characterization of the
      affected individuals in both families was performed with ophthalmic examination,
      electroretinography, electrocardiography, and liver and renal profiling.
      Seventeen genes are known to be associated with BBS, so exome sequencing was
      preferred over candidate gene sequencing. One affected individual from both
      families was selected for exome sequencing. Segregation of the identified
      variants was confirmed with Sanger sequencing. RESULTS: Retinitis pigmentosa,
      obesity, and learning difficulties were present in the affected individuals in
      both families. In family A, a sixth finger (polydactyly) of the proband's sister
      was removed by a surgical operation leaving a scar on the little finger.
      Polydactyly was also present in both affected individuals from family B. All
      diagnostic symptoms were characteristic of BBS in both families. In both affected
      individuals from family A, exome sequencing identified a novel homozygous
      mutation (c.47+1G>T) in BBS1 that inactivates the splice donor site at the end of
      exon 1. In family B, a previously reported mutation, c.442G>A; p.(Asp148Asn), was
      detected. CONCLUSIONS: Exome sequencing is an efficient and cost-effective
      technique for identifying mutations in genetically heterogeneous diseases. In
      addition, intrafamilial phenotypic variability in family A argues for the
      modifying effect of other still unknown modifier alleles.

PMID- 23559860
TI  - Review: Epigenetic mechanisms in ocular disease.
AB  - Epigenetics has become an increasingly important area of biomedical research.
      Increasing evidence shows that epigenetic alterations influence common pathologic
      responses including inflammation, ischemia, neoplasia, aging, and
      neurodegeneration. Importantly, epigenetic mechanisms may have a pathogenic role
      in many complex eye diseases such as corneal dystrophy, cataract, glaucoma,
      diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular
      degeneration. The emerging emphasis on epigenetic mechanisms in studies of eye
      disease may provide new insights into the pathogenesis of complex eye diseases
      and aid in the development of novel treatments for these diseases.

PMID- 23559861
TI  - Association of IL-4 gene VNTR variant with deep venous thrombosis in Behcet's
      disease and its effect on ocular involvement.
AB  - PURPOSE: Behcet's disease (BD) is a systemic vasculitis characterized by
      inflammatory lesions of the urogenital mucosa, eyes, skin, central nervous
      system, and joints. Vein thrombosis constitutes the most frequent vascular
      manifestation of the disease, and may cause such ocular vascular thrombotic
      events as central retinal vein and central retinal artery thrombosis. Thrombosis
      is a serious problem, and often leads to irreversible vision loss. Previous
      studies have shown that genetic factors predispose individuals to BD. Several
      cytokine genes might play crucial roles in host susceptibility to BD and to
      thrombophilia. Various polymorphic regions of the interleukin-4 (IL-4) gene (
      1098G and 590T) are associated with BD in the Turkish population. This study was
      conducted in Turkish patients with BD to determine the frequency of the IL-4 gene
      70 bp variable number of tandem repeats (VNTR) variant, and its association with
      clinical findings. METHODS: Genomic DNA obtained from 488 individuals (238
      patients with Behcet's disease and 250 healthy controls) was used in the study.
      Genomic DNA was isolated and genotyped using PCR assay for the IL-4 gene 70 bp
      VNTR polymorphism determined by using PCR with the specific primers. RESULTS:
      There was statistical significance between the groups regarding IL-4 genotype
      distribution (p<0.001, odds ratio: 2.55 [1.629-4.052], 95% confidence interval)
      and allele frequencies (p<0.0012.381[1.586-3.617], 95% confidence interval). When
      we examined IL-4 genotype frequencies according to the clinical characteristics,
      we observed a statistically significant association between the P2P2 genotype and
      deep venous thrombosis (p=0.01). Deep venous thrombosis was also associated with
      ocular involvement in our study group (p=0.014). CONCLUSIONS: Our findings
      suggest that the IL-4 gene 70 bp VNTR polymorphism is associated with
      susceptibility to development of BD. Deep venous thrombosis is also associated
      with ocular involvement in BD. The IL-4 gene could be a genetic biomarker in
      Behcet's disease in a Turkish study population.

PMID- 23559862
TI  - Altered expression of transforming growth factor beta 1 and matrix
      metalloproteinase-9 results in elevated intraocular pressure in mice.
AB  - PURPOSE: Extracellular matrix remodeling is thought to have profound effects on
      tissue architecture and associated function. We have shown previously that
      overexpression of transforming growth factor beta (TGFbeta), which stimulates
      matrix accumulation, results in altered morphology, cataract, and ocular
      hypertension in rodents. We have further shown that TGFbeta-induced cataracts can
      be mitigated through inhibition of the matrix metalloproteinases (MMP) MMP-2 and
      MMP-9. We therefore sought to determine whether loss of MMP expression also
      altered TGFbeta-induced changes in intraocular pressure (IOP). METHODS: To carry
      out this study, TGFbeta1 transgenic mice were bred onto a MMP-9 null background.
      IOP measurements were made at 1- to 2-, 2- to 3-, and 3- to 4-month time points
      using a TonoLab rebound tonometer. Histological and immunofluorescence findings
      were obtained at the same time points. RESULTS: Our results demonstrate that lens
      specific expression of TGFbeta1 in mice results in altered morphology of the
      anterior segment and an accompanying significant increase in IOP. TGFbeta1
      transgenic mice bred onto the MMP-9 null background exhibited a further increase
      in IOP. Interestingly, the MMP-9-deficient animals (without the TGFbeta
      transgene), which exhibited normal angle morphology, had increased IOP levels
      compared to their wild-type littermates. CONCLUSION: These results indicate that
      TGFbeta and MMP-9 likely act independently in regulating IOP. Additionally, MMP-9
      plays an important role in maintaining IOP, and further investigation into the
      mechanisms of MMP-9 activity in the anterior angle may give clues to how
      extracellular matrix remodeling participates in ocular hypertension and glaucoma.

PMID- 23559863
TI  - Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher
      syndrome type 1.
AB  - PURPOSE: To identify the disease-causing mutation(s) in a Chinese family with
      autosomal recessive Usher syndrome type 1 (USH1). METHODS: An ophthalmic
      examination and an audiometric test were conducted to ascertain the phenotype of
      two affected siblings. The microsatellite marker D11S937, which is close to the
      candidate gene MYO7A (USH1B locus), was selected for genotyping. From the DNA of
      the proband, all coding exons and exon-intron boundaries of MYO7A were sequenced
      to identify the disease-causing mutation(s). Restriction fragment length
      polymorphism (RFLP) analysis was performed to exclude the alternative conclusion
      that the mutations are non-pathogenic rare polymorphisms. RESULTS: Based on
      severe hearing impairment, unintelligible speech, and retinitis pigmentosa, a
      clinical diagnosis of Usher syndrome type 1 was made. The genotyping results did
      not exclude the USH1B locus, which suggested that the MYO7A gene was likely the
      gene associated with the disease-causing mutation(s) in the family. With direct
      DNA sequencing of MYO7A, two novel compound heterozygous mutations (c.3742G>A and
      c.6051+1G>A) of MYO7A were identified in the proband. DNA sequence analysis and
      RFLP analysis of other family members showed that the mutations cosegregated with
      the disease. Unaffected members, including the parents, uncle, and sister of the
      proband, carry only one of the two mutations. The mutations were not present in
      the controls (100 normal Chinese subjects=200 chromosomes) according to the RFLP
      analysis. CONCLUSIONS: In this study, we identified two novel mutations,
      c.3742G>A (p.E1248K) and c.6051+1G>A (donor splice site mutation in intron 44),
      of MYO7A in a Chinese non-consanguineous family with USH1. The mutations
      cosegregated with the disease and most likely cause the phenotype in the two
      affected siblings who carry these mutations compound heterozygously. Our finding
      expands the mutational spectrum of MYO7A.

PMID- 23559864
TI  - Pharmacogenetic association with early response to intravitreal ranibizumab for
      age-related macular degeneration in a Korean population.
AB  - PURPOSE: To determine whether genetic factors that influence age-related macular
      degeneration (AMD) have an early pharmacogenetic effect on treating exudative AMD
      with ranibizumab in a Korean population. METHODS: A retrospective study of 102
      patients (70 with typical neovascular AMD and 32 with polypoidal choroidal
      vasculopathy) with exudative AMD treated with intravitreal ranibizumab
      monotherapy was conducted. Optical coherence tomography, fluorescein, and
      indocyanine green angiography were taken at the baseline. The best-corrected
      visual acuity (BCVA) and the central subfield macular thickness (CSMT) were
      recorded at the baseline and at each monthly visit. The genotypes of the
      polymorphisms in the known AMD susceptibility loci (CFH, AMRS2, HTRA1, VEGFA, and
      KDR) were determined, and association between their frequencies and the changes
      in the BCVA and the CSMT were evaluated. RESULTS: The mean baseline visual acuity
      was 0.96 +/- 0.59 logMAR (approximately 20/200 in the Snellen equivalent), and
      the mean number of injections was 3.87 before the month 6 visit. No association
      was observed between the change in BCVA and each genotype. For the changes in the
      CSMT, a significant difference was observed only with the VEGF-A (rs833069) gene.
      The decrease in the CSMT at month 3 for the major allele homozygote AA genotype,
      the heterozygote AG genotype, and the risk allele homozygote GG genotype was
      25.66 +/- 85.40, 86.93 +/- 92.31, and 85.30 +/- 105.30 MUm, respectively
      (p=0.012, p=0.044, and p=0.002 for AG, GG, and combined AG or GG genotype,
      respectively, compared to the AA genotype). This trend was maintained until month
      6. CONCLUSIONS: The VEGF-A (rs833069) polymorphism showed a significant
      association with the anatomic response to intravitreal ranibizumab. No
      significant difference was found between the genotype of the potential risk
      polymorphism for development of AMD and the early visual improvement after
      intravitreal ranibizumab.

PMID- 23559865
TI  - Association of Pro12Ala polymorphism in peroxisome proliferator activated
      receptor gamma with proliferative diabetic retinopathy.
AB  - PURPOSE: The association of non-synonymous substitution polymorphism rs1801282
      (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor
      gamma gene with diabetic retinopathy (DR) has been reported inconsistently.
      Therefore, the purpose of the present study was to understand the population
      specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani
      subjects. METHODS: A total of 180 subjects with DR, 193 subjects with type 2
      diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy
      normoglycemic non-retinopathic Pakistani individuals were genotyped for the
      rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction
      fragment length polymorphism. RESULTS: We found the individuals with T2DM
      carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95%
      confidence interval [CI]=0.33-0.87). Upon stratified analysis regarding disease
      severity, we observed this protective effect was confined to proliferative DR
      (OR=0.4; 95% CI=0.2-0.8) with non-significant effects on the susceptibility of
      non-proliferative DR (OR=0.67; 95% CI=0.37-1.19). CONCLUSIONS: We report a
      protective role of the 12Ala polymorphism against proliferative DR in individuals
      with T2DM in Pakistan.

PMID- 23559866
TI  - Altered cytokine profiles of human retinal pigment epithelium: oxidant injury and
      replicative senescence.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a local, chronic inflammatory
      disease of the eye that is influenced by oxidative stress and dysregulation of
      the retinal pigment epithelium (RPE) associated with aging. The purpose of this
      study is to characterize the effects of oxidative stress and replicative
      senescence on the secreted cytokine profiles of RPE in vitro. METHODS: We used
      multiple, serial passages of human RPE cells from primary culture as an in vitro
      model of aging. Responses of early passage 5 (P5) and late passage 21 (P21) RPE
      cells were compared. Oxidative stress was induced in RPE cells (P5) by exposure
      to 75 MUM hydroquinone (HQ) for 24 h. The secretome profiles of the RPE cells
      were measured with a multiplex suspension assay that assayed human cytokine,
      chemokine, and growth factors. Immunohistochemistry on younger (<=55 years old)
      and older (>=70 years old) human post-mortem donor eyes was used to verify
      selected cytokines. RESULTS: Supernatant of HQ-treated RPE cultures exhibited
      increased secreted levels of vascular endothelial growth factor (VEGF),
      interleukin (IL)-12, and IL-10 that reached statistical significance (p<0.05).
      Supernatant of late passage P21 RPE cultures exhibited decreased secreted levels
      of stromal cell-derived factor (SDF)-1alpha, granulocyte macrophage colony
      stimulating factor (GM-CSF), IL-8, IL-15, IL-6, and an increased level of IL-1ra
      compared to early passage P5 RPE cultures that reached statistical significance
      (p<0.05). Immunohistochemical analysis demonstrated increased expression of IL
      1ra in RPE cells from older post-mortem donor eyes (>=70 years old) versus
      younger eyes (<=55 years old). CONCLUSIONS: Our data demonstrate a unique
      cytokine secretion profile of primary culture RPE cells at early and late
      passage. Our in vitro data suggest an age-specific modulation of cytokine
      secretion in RPE and is consistent with immunohistochemical analysis on post
      mortem eyes. The secretion profile associated with RPE under conditions that
      mimic oxidative stress, another factor associated with the pathogenesis of AMD,
      emphasizes upregulation of the angiogenic growth factor, vascular endothelial
      growth factor. Together, these data support the role of advanced age and
      oxidative stress in inflammatory cytokine modulation in RPE cells.

PMID- 23559867
TI  - Serum levels of matrix metalloproteinase 2 and matrix metalloproteinase 9
      elevated in polypoidal choroidal vasculopathy but not in age-related macular
      degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) and polypoidal choroidal
      vasculopathy (PCV) are the leading causes of vision loss in the elderly Asian
      population. Previous studies have confirmed that abnormal extracellular matrix
      (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV.
      However, the dynamic metabolism of the ECM is closely regulated by matrix
      metalloproteinases (MMPs) and tissue metalloproteinase inhibitors (TIMPs).
      Whether MMPs and TIMPs participate in the pathogenesis of AMD and PCV remains
      unclear. The aim of this study was to investigate the correlation between
      circulating MMP and TIMP levels and AMD and PCV. METHODS: The serum levels of
      MMPs (MMP1, MMP2, MMP3, and MMP9) and TIMPs (TIMP1 and TIMP3) were quantified
      using enzyme-linked immunosorbent assays in four groups of subjects (n=342):
      early AMD (group 1, n=75), neovascular AMD (group 2, n=89), PCV (group 3, n=98),
      and age- and gender-matched controls (group 4, n=80). RESULTS: The mean
      concentrations of the two gelatinases, MMP2 and MMP9, in the PCV group were
      significantly higher than that of the control (p=0.001, p<0.001, respectively),
      early AMD (both p<0.001), and neovascular AMD (p=0.005, p=0.001, respectively)
      groups. Moreover, the serum MMP2 concentration was positively correlated with the
      serum MMP9 concentration in the PCV group (r=0.822, p<0.001). However, the mean
      concentrations of MMP2 and MMP9 in the early AMD and neovascular AMD groups were
      not significantly different from that of the control group (p>0.05). The mean
      serum levels of MMP1, MMP3, TIMP1, and TIMP3 were not significantly different
      among the four groups. CONCLUSIONS: This pilot study first reveals a link between
      increased levels of circulating gelatinases (MMP2 and MMP9) and PCV but not AMD,
      which may provide a biologically relevant marker of ECM metabolism in patients
      with PCV. This finding suggests that the two disorders may have different
      molecular mechanisms.

PMID- 23559868
TI  - Cancer narratives: words beyond disease-a call for submissions.

PMID- 23559869
TI  - Many mosaic mutations.

PMID- 23559870
TI  - Countercurrents: A new kind of breast cancer gene mutation: A Countercurrents
      Series.

PMID- 23559871
TI  - Assessing fitness to drive in brain tumour patients: a grey matter of law,
      ethics, and medicine.
AB  - BACKGROUND: Neurocognitive deficits from brain tumours may impair the ability to
      safely operate a motor vehicle. Although certain jurisdictions in Canada legally
      require that physicians report patients who are unfit to drive, criteria for
      determining fitness are not clearly defined for brain tumours. METHODS: Patients
      receiving brain radiotherapy at our institution from January to June 2009 were
      identified using the Oncology Patient Information System. In addition to
      descriptive statistics, details of driving assessment were reviewed
      retrospectively. The Fisher exact test was used to determine factors predictive
      of reporting a patient to the Ontario Ministry of Transportation (mto) as unfit
      to drive. A logistic regression model was constructed to further determine
      factors predictive of reporting. RESULTS: Of the 158 patients available for
      analysis, 48 (30%) were reported to the mto, and 64 (41%) were advised to stop
      driving. With respect to the 53 patients with seizures, a report was submitted to
      the mto for 30 (57%), and a documented discussion about the implications of
      driving was held with 35 (66%). On univariate analysis, younger age, a central
      nervous system primary, higher brain radiotherapy dose, unifocal disease, and the
      presence of seizures were predictive of physician reporting (p < 0.05). On
      logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a
      higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting.
      INTERPRETATION: Physicians frequently do not discuss the implications of driving
      with brain tumour patients or are not properly documenting such advice (or both).
      Clear and concise reporting guidelines need to be drafted given the legal,
      medical, and ethical concerns surrounding this public health issue.

PMID- 23559872
TI  - Evaluation of the clinical benefits of nanoparticle albumin-bound paclitaxel in
      women with metastatic breast cancer in British Columbia.
AB  - BACKGROUND: Altered formulations of taxanes may lack cross-resistance with
      standardly used solvent-based taxanes. The primary objective of the present study
      was to assess the clinical benefit of nanoparticle albumin-bound (nab)-paclitaxel
      in women with metastatic breast cancer previously treated with and without
      adjuvant taxane in British Columbia. METHODS: The BC Cancer Agency Pharmacy data
      repository and Breast Cancer Outcomes Unit database were linked to identify all
      patients who received nab-paclitaxel in British Columbia since its introduction
      in 2007. Hormone receptor status, demographic characteristics, number of cycles
      prescribed, and time to treatment failure were extracted and analyzed. RESULTS:
      From 2007 to 2011, 138 patients in British Columbia received nab-paclitaxel, with
      122 patients available for analysis. Most (70.5%) received adjuvant chemotherapy;
      about a quarter (24.6%) received an adjuvant taxane. Patients who received
      adjuvant taxane were more likely to have node-positive (86.7% vs. 48.9%, p =
      0.007), estrogen receptor-negative (46.7% vs. 13.0% p < 0.001) disease and to
      receive initial adjuvant radiotherapy (76.7% vs. 51.1%, p < 0.001). For the
      entire cohort, the median number of nab-paclitaxel cycles prescribed was 4.4
      (range: 0.3-13). The median number of nab-paclitaxel cycles was greater when that
      agent was given as first- or second-line therapy than as third-line or greater
      therapy (5.0 cycles vs. 3.7 cycles respectively). The median time to treatment
      failure was 96 days in the prior adjuvant taxane group (range: 0-361) and 73.5
      days in the no prior adjuvant taxane group (range: 0-1176). CONCLUSIONS: This
      retrospective study demonstrates potential clinical activity of nab-paclitaxel in
      metastatic breast cancer regardless of whether patients had prior exposure to
      adjuvant taxanes.

PMID- 23559873
TI  - Analysis of intraprostatic therapeutic effects in prostate cancer patients using
      [(11)C]-choline pet/ct after external-beam radiation therapy.
AB  - PURPOSE: The objective of the present study was to analyze, with relatively high
      sensitivity and specificity, uptake properties of [(11)C]-choline in prostate
      cancer patients by means of positron-emission tomography (pet)/computed
      tomography (ct) imaging using objectively defined pet parameters to test for
      statistically significant changes before, during, and after external-beam
      radiation therapy (ebrt) and to identify the time points at which the changes
      occur. METHODS: The study enrolled 11 patients with intermediate-risk prostate
      cancer treated with ebrt, who were followed for up to 12 months after ebrt. The
      [(11)C]-choline pet scans were performed before treatment (baseline); at weeks 4
      and 8 of ebrt; and at 1, 2, 3, 6, and 12 months after ebrt. RESULTS: Analysis of
      [(11)C]-choline uptake in prostate tissue before treatment resulted in a maximum
      standardized uptake value (suvmax) of 4.0 +/- 0.4 (n = 11) at 40 minutes after
      injection. During week 8 of ebrt, the suvmax declined to 2.9 +/- 0.1 (n = 10, p <
      0.05). At 2 and 12 months after ebrt, suvmax values were 2.3 +/- 0.3 (n = 10, p <
      0.01) and 2.2 +/- 0.2 (n = 11, p < 0.001) respectively, indicating that, after
      ebrt, maximum radiotracer uptake in the prostate was significantly reduced.
      Similar effects were observed when analyzing the tumour:muscle ratio (tmr). The
      tmr declined from 7.4 +/- 0.6 (n = 11) before ebrt to 6.1 +/- 0.4 (n = 11,
      nonsignificant) during week 8 of ebrt, to 5.6 +/- 0.03 (n = 11, p < 0.05) at 2
      months after ebrt, and to 4.4 +/- 0.4 (n = 11, p < 0.001) at 12 months after
      ebrt. CONCLUSIONS: Our study demonstrated that intraprostatic [(11)C]-choline
      uptake in the 11 analyzed prostate cancer patients significantly declined during
      and after ebrt. The pet parameters SUVmax and tmr also declined significantly.
      These effects can be detected during radiation therapy and up to 1 year after
      therapy. The prognostic value of these early and statistically significant
      changes in intraprostatic [(11)C]-choline pet avidity during and after ebrt are
      not yet established. Future studies are indicated to correlate changes in [(11)C]
      choline uptake parameters with long-term biochemical recurrence to further
      evaluate [(11)C]-choline pet changes as a possible, but currently unproven,
      biomarker of response.

PMID- 23559874
TI  - What is the burden of axillary disease after neoadjuvant therapy in women with
      locally advanced breast cancer?
AB  - BACKGROUND: The burden of axillary disease in patients with locally advanced
      breast cancer (labc) after neoadjuvant therapy (nat) has not been extensively
      described in a large modern cohort. Here, we describe the extent of nodal
      metastases after nat in patients with labc. METHODS: All patients with labc
      treated at a single institution during 2002-2007 were identified. Demographic,
      radiologic, and pathologic variables were extracted. To assess the extent of
      lymph node metastases after nat, patients were separated into two groups: those
      with and without clinical or radiologic evidence of lymph node metastases before
      nat. Axillary lymph nodes retrieved at surgery that had no evidence of metastases
      after hematoxylin and eosin (h&e) staining underwent further pathology
      evaluation. RESULTS: Of the 116 patients identified, 115 were female (median age:
      48.5). Before nat, 26 patients were clinically and radiologically node-negative;
      of those 26, 14 were histologically negative on final pathology. After serial
      sectioning and immunohistochemistry, 9 of 26 (35%) were node-negative. Of the 90
      patients who had clinical or radiologic evidence of lymph node metastases before
      nat, 23 (26%) had no evidence of lymph node metastases on h&e staining. After
      serial sectioning and immunohistochemistry, 19 (21%) had no further axillary
      lymph node metastases. Overall, 76% of patients had pathology evidence of lymph
      node metastases after nat. CONCLUSIONS: Most patients with labc have axillary
      metastases after nat. Our findings support axillary lymph node dissection and
      locoregional radiation in most patients with labc after nat.

PMID- 23559875
TI  - New chart review data validate administrative data-based indicator for guideline
      recommended treatment of locally advanced non-small-cell lung cancer and shed
      light on reasons for non-referral and non-treatment.

PMID- 23559876
TI  - Informing Canada's cancer drug funding decisions with scientific evidence and
      patient perspectives: the Pan-Canadian Oncology Drug Review.

PMID- 23559877
TI  - A real-life experience using panitumumab in chemo-refractory metastatic
      colorectal cancer patients: a retrospective analysis at the Jewish General
      Hospital, 2009-2012.
AB  - BACKGROUND: Panitumumab is a fully human monoclonal antibody, directed against
      the epidermal growth factor receptor, that was shown to be effective in third
      line metastatic colorectal cancer. We performed a retrospective analysis of
      patients with chemo-refractory non-KRAS-mutated metastatic colorectal cancer, who
      received panitumumab at the Jewish General Hospital in Montreal, Canada, between
      2009 and 2012. METHODS: This chart review included 44 patients (median age: 60
      years; performance status: 0-3), of whom 50% had already received three lines of
      treatment. The primary endpoint was progression-free survival (pfs). Secondary
      endpoints were overall survival and safety. Tumour progression was determined by
      radiologic assessments performed once every 3 months per clinical guidelines or
      by clinical deterioration as determined by the clinician-investigator. RESULTS:
      In our sample, median pfs was 21.86 +/- 5.23 weeks (95% confidence interval: 12.9
      to 36.9 weeks) and overall survival was 35.14 +/- 7.75 weeks (95% confidence
      interval: 25.6 to 73.4 weeks) with a median of 5 cycles of panitumumab treatment.
      The most frequently reported toxicities with panitumumab were skin toxicity
      (16.2% grade 3) and hypomagnesemia (10.8% grade 3). No infusion reactions were
      reported. CONCLUSIONS: Despite a small sample size from a single institution, our
      survival and efficacy data are encouraging and comparable to results obtained
      from the registration panitumumab trial. Our findings suggest that panitumumab
      can be effective and tolerable in a real-world setting.

PMID- 23559878
TI  - Primary lymphoepithelioma-like carcinoma of ocular adnexa: clinicopathologic
      features and treatment.
AB  - BACKGROUND AND METHODS: Lymphoepithelioma-like carcinoma (lelc) is a rare
      malignancy in ocular adnexa. Here, we report 4 patients with lelc and review 11
      patients reported in the literature. Clinical profiles, association with Epstein
      Barr virus (ebv), treatment, and outcomes are analyzed. RESULTS: Lacrimal glands
      and the lacrimal drainage system, eyelid, and conjunctiva are potential primary
      sites for lelc. The tumours are characterized histologically by nests of
      undifferentiated malignant cells surrounded by lymphoid infiltrates. Infection
      with ebv was confirmed in lelc of ocular adnexa, and that association seemed to
      be restricted to Asian populations. Results from our centre uniformly showed
      expression of ebv-encoded small rnas in primary tumour, locally recurrent tumour,
      and metastatic lymph nodes. This disease had a tendency to relapse regionally.
      Postoperative radiotherapy seems to improve disease-free survival. Tumours appear
      to be sensitive to radiotherapy and chemotherapy based on cisplatin and 5
      fluorouracil. At our centre, 3 patients were still living at 22, 33, and 76
      months after surgery. One patient died of distant metastasis after a survival of
      38 months. CONCLUSIONS: Lymphoepithelioma-like carcinoma is a heterogenous entity
      among ocular adnexal malignancies. Multimodality treatment provides a better
      chance at survival. Further investigation is required to achieve a better
      understanding of the biologic behavior of this entity and of its optimal
      treatment.

PMID- 23559879
TI  - Impact of a single-day multidisciplinary clinic on the management of patients
      with liver tumours.
AB  - PURPOSE: Multidisciplinary cancer clinics may improve patient care. We examined
      how a single-day multidisciplinary liver clinic (mdlc) affected care
      recommendations for patients compared with the recommendations provided before
      presentation to the mdlc. METHODS: We analyzed the demographic and
      clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor
      Center from 2009 to 2012, comparing imaging and pathology interpretation,
      diagnosis, and management plan between the outside provider (osp) and the mdlc.
      RESULTS: Most patients were white (n = 259, 76%); median age was 60 years; and
      146 were women (43%). Outside providers referred 182 patients (53%); the rest
      were self-referred. Patients travelled median of 83.4 miles (interquartile range:
      42.7-247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n
      = 194, 57%) at the osp, and a formal management plan had been formulated for
      about half (n = 168, 49%). Alterations in the interpretation of imaging occurred
      for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the mdlc
      resulted in a change of diagnosis in 26 patients (8%), of management plan in 70
      patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the
      patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%)
      received treatment, primarily intraarterial therapy (n = 88, 57%), systemic
      chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a
      clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were
      accrued. CONCLUSIONS: Patient assessment by our multidisciplinary liver clinic
      had a significant impact on management, resulting in alterations to imaging and
      pathology interpretation, diagnosis, and management plan. The mdlc is an
      effective and convenient means of delivering expert opinion about the diagnosis
      and management of liver tumours.

PMID- 23559880
TI  - Role of endolaryngeal surgery (with or without laser) compared with radiotherapy
      in the management of early (T1) glottic cancer: a clinical practice guideline.
AB  - AIMS: To provide evidence-based practice guideline recommendations concerning the
      role of endolaryngeal surgery (with or without laser) compared with radiation
      therapy for patients with early (T1) glottic cancer, assessing survival,
      locoregional control, laryngeal preservation rates, and voice outcomes. METHODS:
      The medline, embase, and Cochrane Library databases were searched to identify
      relevant studies from 1996 to 2011. Recommendations were formulated based on that
      evidence and on the expert opinion of Cancer Care Ontario's Head and Neck Cancer
      disease site group. The systematic review and practice guideline were externally
      reviewed by practitioners in Ontario, Canada. RESULTS: The available evidence was
      of a level insufficient to demonstrate a clear difference between treatment
      options when considering the likelihood of local control or overall survival.
      Although the evidence was mainly retrospective, there was a suggestion that,
      compared with surgery, radiotherapy might be associated with less measureable
      perturbation of voice without a significant difference in patient perception. The
      likelihood of laryngeal preservation may be higher when surgery can be offered as
      initial treatment. CONCLUSIONS: For patients with early (T1) glottic cancer, the
      evidence is insufficient to demonstrate a difference between endolaryngeal
      surgery (with or without laser) and external-beam radiation therapy. The choice
      between treatment modalities has been based on patient and clinician preferences
      and general medical condition.

PMID- 23559881
TI  - Lenalidomide in multiple myeloma-a practice guideline.
AB  - BACKGROUND: Promising new drugs such as lenalidomide, an immunomodulatory agent,
      are available for the treatment of multiple myeloma. We describe the process of
      creating a provincial guideline for the use of lenalidomide, alone or in
      combination with other drugs, in relapsed, refractory, or newly diagnosed disease
      (including smoldering and symptomatic patients, and candidates and non-candidates
      for transplant) and in maintenance treatment (after transplant or non-transplant
      therapy); and for strategies to manage lenalidomide-related toxicities. METHODS:
      Outcomes of interest included overall survival, event-free survival, progression
      free survival, time to progression, time to next treatment, response rate, and
      incidence of serious toxicity. The medline, embase, and Cochrane Library
      databases, as well as meeting abstracts and the Web sites of relevant
      organizations, were systematically searched for relevant literature. RESULTS:
      Recommendations were developed using the evidence from published studies and the
      clinical expertise of the working group and of the Cancer Care Ontario Hematology
      Disease Site Group. CONCLUSIONS: Lenalidomide in combination with dexamethasone
      can be recommended for both previously untreated and treated patients with
      multiple myeloma. Guidelines for the management of cytopenias, venous
      thromboembolism, and second primary malignancies are discussed.

PMID- 23559882
TI  - Overall survival should be the primary endpoint in clinical trials for advanced
      non-small-cell lung cancer.
AB  - An article in a recent edition of Current Oncology explored the validation of
      progression-free survival (pfs) as an endpoint in clinical trials of
      antineoplastic agents for metastatic colorectal cancer, metastatic renal cell
      carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for
      overall survival (os) was elucidated. As with the aforementioned tumour types,
      advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents
      since the year 2000. Those agents range from improved cytotoxics such as
      pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the
      epidermal growth factor receptor and agents that target the EML4-ALK gene
      mutation. More recently, it has also become apparent that histology plays an
      important role in the response to and outcomes of treatment. With the therapeutic
      options for patients with advanced nsclc increasing, concerns are being raised
      that the efficacy of drugs measured by os may be diluted in clinical trials,
      thereby underestimating their true clinical benefit. That possibility, together
      with the need to have efficacious drugs available to patients earlier, has
      resulted in the search for a surrogate to the os endpoint in advanced nsclc. The
      present article follows up the recent article on pfs as a surrogate. Although
      advances in identifying pfs as a valid surrogate endpoint for os have been made
      in other tumour types, in advanced nsclc, such surrogacy has not been formally
      validated. Until it has, os should remain the primary endpoint of clinical trials
      in advanced nsclc.

PMID- 23559883
TI  - Case report of very late gastric cancer recurrence.
AB  - Very late recurrence of gastric cancer is rare. Here, we report a dramatic
      recurrence of gastric cancer, with isolated skeletal metastasis and bone marrow
      carcinomatosis, 22 years after the patient's initial presentation. Gastric cancer
      recurrence involving bone or bone marrow is also uncommon and associated with
      poor prognosis. Pathology from a bone marrow biopsy showed signet ring cell
      morphology. The patient in this case demonstrated a surprising response-lasting
      11 months-to palliative chemotherapy with cisplatin and capecitabine. This case
      report and literature review describes the characteristics of late gastric cancer
      recurrence and an approach to the diagnosis and management of patients with bone
      metastasis or bone marrow carcinomatosis.

PMID- 23559884
TI  - Immune toxicities and long remission duration after ipilimumab therapy for
      metastatic melanoma: two illustrative cases.
AB  - New antitumour immunotherapy strategies for stage iv metastatic melanoma include
      ipilimumab, a monoclonal antibody against ctla-4. Patterns of response with
      cancer immunotherapy differ from those with cytotoxic chemotherapy. We present
      two cases of long-duration immune-related responses with ipilimumab in a phase ii
      trial. A 66-year-old woman with multiple lung metastases from a scalp primary
      melanoma received 4 doses of ipilimumab with mixed clinical response. However,
      after the first maintenance dose, she developed severe ileitis and colitis that
      responded to steroid therapy. Four months later, she had surgery and radiotherapy
      for a single brain metastasis. Radiologically, stable disease continued for 36
      months after the last ipilimumab dose, and partial response for 5 years after
      ipilimumab start. A 54-year-old man with cervical lymph node and pulmonary
      metastases from a scalp primary melanoma received three induction doses of
      ipilimumab. He developed alopecia universalis and widespread vitiligo, and he
      discontinued treatment because of hypophysitis. Maintenance ipilimumab was
      started after a 6-month drug-free interval, with no further adverse events over
      15 cycles. At week 12, computed tomography imaging showed no lung metastases and
      partial response in a supraclavicular lymph node, which was positive on positron
      emission tomography. Five years after starting ipilimumab, the supraclavicular
      lymph node was calcified, and the patient was off steroid therapy and
      asymptomatic. The foregoing patients demonstrate long responses with ipilimumab
      (in association with delayed severe colitis in one case, and a constellation of
      immune events, including alopecia universalis in another). Re-treatment with
      ipilimumab may be possible even after significant immune adverse events.

PMID- 23559885
TI  - The growing pains of cancer survivors: a call for a paradigm of interdisciplinary
      care.

PMID- 23559886
TI  - Genetically modified foods, cancer, and diet: myths and reality.

PMID- 23559887
TI  - The Current Oncology Scholar's Forum and Workshop.

PMID- 23559888
TI  - Breast cancer survivorship and South Asian women: understanding about the follow
      up care plan and perspectives and preferences for information post treatment.
AB  - BACKGROUND AND OBJECTIVES: As more treatment options become available and
      supportive care improves, a larger number of people will survive after treatment
      for breast cancer. In the present study, we explored the experiences and concerns
      of female South Asian (sa) breast cancer survivors (bcss) from various age groups
      after treatment to determine their understanding of follow-up care and to better
      understand their preferences for a survivorship care plan (scp). METHODS:
      Patients were identified by name recognition from BC Cancer Agency records for sa
      patients who were 3-60 months post treatment, had no evidence of recurrence, and
      had been discharged from the cancer centre to follow-up. Three focus groups and
      eleven face-to-face semistructured interviews were audio-recorded, transcribed
      verbatim, cross-checked for accuracy, and analyzed using thematic and content
      analysis. Participants were asked about their survivorship experiences and their
      preferences for the content and format of a scp. RESULTS: Fatigue, cognitive
      changes, fear of recurrence, and depression were the most universal effects after
      treatment. "Quiet acceptance" was the major theme unique to sa women, with a
      unique cross-influence between faith and acceptance. Emphasis on a generalized
      scp with individualized content echoed the wide variation in breast cancer
      impacts for sa women. Younger women preferred information on depression and peer
      support. CONCLUSIONS: For sa bcss, many of the psychological and physical impacts
      of breast cancer diagnosis and treatment may be experienced in common with bcss
      of other ethnic backgrounds, but the present study also suggests the presence of
      unique cultural nuances such as spiritual and language-specific support resource
      needs. The results provide direction for designing key content and format of
      scps, and information about elements of care that can be customized to individual
      patient needs.

PMID- 23559889
TI  - Perceptions of survivorship care among South Asian female breast cancer
      survivors.
AB  - BACKGROUND AND OBJECTIVES: To explore the perceptions of South Asian (sa) breast
      cancer survivors concerning their follow-up care, and to determine the optimal
      content and format of a survivorship care plan (scp) for this population,
      according to various life stages. METHODS: A survey was mailed to 259 sa women
      with a diagnosis of nonmetastatic breast cancer who were 18-85 years of age, 3-60
      months post-discharge, and not on active treatment. Descriptive statistics and
      content analysis were applied to the responses. The data were cross-tabulated by
      age: group A (<44 years), group B (45-54 years), group C (55-64 years), and group
      D (>64 years). RESULTS: We received 64 completed surveys. The compliance rate for
      adjuvant hormonal therapy was high (86.3%). Most of the respondents (n = 61,
      95.4%) had visited their family doctor within several months (0.5-24 months)
      after discharge. Their main physical effects concern was fatigue, and anxiety
      concerning health was the main psychosocial impact. Groups A and B were more
      concerned about physical appearance, depression, and the impact of cancer on
      family members. Women in the older groups were concerned about family obligations
      and work issues. Several women (n = 9, 14.1%) described strain on their marriage
      and on their relationships with family and friends as significant issues.
      Slightly more than one third (n = 24, 37.5%) experienced a deepening of faith,
      and almost as many (n = 23, 35.9%) felt that their illness was something that was
      meant to happen. CONCLUSIONS: Many of the impacts of breast cancer treatment are
      shared by women of all ethnic backgrounds. Others-such as high levels of
      compliance, little reported strain on spousal and family relationships, and the
      importance of faith-reflect specific cultural variations. These universal and
      culture-specific themes should all be kept in mind when developing a scp tailored
      to sa women. The developmental life stage of a woman affects how she views the
      cancer diagnosis, especially with respect to family, reproduction, and work
      issues.

PMID- 23559890
TI  - Cost-effectiveness of systemic therapies for metastatic pancreatic cancer.
AB  - PURPOSE: Gemcitabine and capecitabine (gem-cap), gemcitabine and erlotinib (gem
      e), and folfirinox (5-fluorouracil-leucovorin-irinotecan-oxaliplatin) are new
      treatment options for metastatic pancreatic cancer, but they are also more
      expensive and potentially more toxic than gemcitabine alone (gem). We conducted a
      cost-effectiveness analysis of these treatment options compared with gem.
      METHODS: A Markov model was constructed to examine costs and outcomes of gem-cap,
      gem-e, folfirinox, and gem in patients with metastatic pancreatic cancer from the
      perspective of a government health care plan. Ontario health economic and costing
      data (2010 Canadian dollars) were used. Efficacy data for the treatments were
      obtained from the published literature. Resource utilization data were derived
      from a chart review of consecutive metastatic patients treated for pancreatic
      cancer at Princess Margaret Hospital, Toronto, Ontario, 2008-2009, and
      supplemented with data from the literature. Utilities were obtained by surveying
      medical oncologists across Canada using the EQ-5D. Incremental cost-effectiveness
      ratios (icers) were calculated. RESULTS: The icers for gem-cap, gem-e, and
      folfirinox compared with gem were, respectively, CA$84,299, CA$153,631, and
      CA$133,184 per quality-adjusted life year (qaly). The model was driven mostly by
      drug acquisition costs. Given a willingness-to-pay (wtp) threshold greater than
      CA$130,000/qaly, folfirinox was most cost-effective treatment. When the wtp
      threshold was less than CA$80,000/qaly, gem alone was most cost-effective. The
      gem-e option was dominated by the other treatments. CONCLUSIONS: The most cost
      effective treatment for metastatic pancreatic cancer depends on the societal wtp
      threshold. If the societal wtp threshold were to be relatively high or if drug
      costs were to be substantially reduced, folfirinox might be cost-effective.

PMID- 23559891
TI  - Gender Differences in Psychiatric Symptoms among Methamphetamine Dependent
      Residents in Sober Living Houses.
AB  - OBJECTIVES: Although psychiatric symptoms among methamphetamine (MA) dependent
      individuals have been studied in treatment programs, they have not been examined
      in services designed to support sustained recovery in the community (e.g. sober
      living houses). In addition, some disorders more common among women, such as
      somatoform and bulimia, have been understudied among MA dependent individuals.
      This study aimed to examine psychiatric symptom differences between MA dependent
      men and women who we entering sober living houses (SLHs). METHODS: Two hundred
      forty five individuals were interviewed within one week of entering SLHs.
      Instruments included a DSM IV based measure for MA dependence, a psychiatric
      screen (the Psychiatric Diagnostic Screening Questionnaire), demographics, recent
      substance use and recent use of services. RESULTS: Of the 245 participants, 103
      men and 25 women met criteria for MA dependence. Womenwith MA dependence reported
      more psychiatric symptoms than men. They also trended toward reporting more
      psychiatric symptoms than non-MA dependent women. For men, psychiatric symptoms
      did not vary between those with and without MA dependence. Some understudied
      disorders (e.g., somatoform) had large proportions of women meeting the screening
      criteria. CONCLUSIONS: Additional research is needed on understudied psychiatric
      disorders that are common among MA dependent women. SLH's should consider ways to
      address psychiatric symptoms among MA dependent individuals, especially women.
      Strategies could include increasing linkages with professional mental health
      services as well as developing peer oriented strategies for managing symptoms.

PMID- 23559892
TI  - Development of a Brief Abstinence Self-Efficacy Measure.
AB  - This study compared the 40-item Alcohol Abstinence Self-Efficacy (AASE) scale
      with domains of confidence and temptation to a new 12-item version developed by
      the authors consisting of the same domains. There were 126 participants who
      completed the survey. Psychometric analysis demonstrated high reliability and
      validity consisting of high correlations between domains of confidence (alpha =
      .92) and temptation (alpha = .88) in the 40-item version of the scale compared to
      the briefer version. The 12-item version appears to provide a clinically reliable
      and valid measure of AASE domains of confidence and temptation, providing a more
      efficient tool for clinical practice.

PMID- 23559894
TI  - Autophagy as an innate immune modulator.
AB  - Autophagy is a fundamental cellular process in eukaryotic cells for maintaining
      homeostasis by degrading cellular proteins and organelles. Recently, the roles of
      autophagy have been expanded to immune systems, which in turn modulate innate
      immune responses. More specifically, autophagy acts as a direct effector for
      protection against pathogens, as well as a modulator of pathogen recognition and
      downstream signaling in innate immune responses. In addition, autophagy controls
      autoimmunity and inflammatory disorders by negative regulation of immune
      signaling. In this review, we focus on recent advances in the role of autophagy
      in innate immune systems.

PMID- 23559893
TI  - Assessment of cognition in early dementia.
AB  - Better tools for assessing cognitive impairment in the early stages of
      Alzheimer's disease (AD) are required to enable diagnosis of the disease before
      substantial neurodegeneration has taken place and to allow detection of subtle
      changes in the early stages of progression of the disease. The National Institute
      on Aging and the Alzheimer's Association convened a meeting to discuss state of
      the art methods for cognitive assessment, including computerized batteries, as
      well as new approaches in the pipeline. Speakers described research using novel
      tests of object recognition, spatial navigation, attentional control, semantic
      memory, semantic interference, prospective memory, false memory and executive
      function as among the tools that could provide earlier identification of
      individuals with AD. In addition to early detection, there is a need for
      assessments that reflect real-world situations in order to better assess
      functional disability. It is especially important to develop assessment tools
      that are useful in ethnically, culturally and linguistically diverse populations
      as well as in individuals with neurodegenerative disease other than AD.

PMID- 23559895
TI  - Alum Directly Modulates Murine B Lymphocytes to Produce IgG1 Isotype.
AB  - Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines.
      Nevertheless, it is virtually unknown whether alum acts on B cells. In the
      present study, we explored the direct effect of alum on Ig expression by murine B
      cells in vitro. LPS-activated mouse spleen B cells were cultured with alum, and
      the level of isotype-specific Ig secretion, IgG1 secreting cell numbers, and Ig
      germ-line transcripts (GLT) were measured using ELISA, ELISPOT, and RT-PCR,
      respectively. Alum consistently enhanced total IgG1 production, numbers of IgG1
      secreting cells, and GLTgamma1 expression. These results demonstrate that alum
      can directly cause IgG1 isotype switching leading to IgG1 production.

PMID- 23559896
TI  - Functional Characteristics of C-terminal Lysine to Cysteine Mutant Form of CTLA
      4Ig.
AB  - CTLA-4Ig is regarded as an inhibitory agent of the T cell proliferation via
      blocking the costimulatory signal which is essential for full T cell activation.
      To improve applicability, we developed the CTLA-4Ig-CTKC in which the c-terminal
      lysine had been replaced by cysteine through single amino acid change. The single
      amino acid mutation of c-terminus of CTLA-4Ig was performed by PCR and was
      checked by in vitro transcription and translation. DNA construct of mutant form
      was transfected to Chinese hamster ovary (CHO) cells by electroporation. The
      purified proteins were confirmed by Western blot and B7-1 binding assay for their
      binding ability. The suppressive capacity of CTLA-4Ig-CTKC was evaluated by the
      mixed lymphocyte reaction (MLR) and in the allogeneic pancreatic islet
      transplantation model. CTLA-4Ig-CTKC maintained binding ability to B7-1 molecule
      and effectively inhibits T cell proliferation in MLR. In the murine allogeneic
      pancreatic islet transplantation, short-term treatment of CTLA-4Ig-CTKC prolonged
      the graft survival over 100 days. CTLA-4Ig-CTKC effectively inhibits immune
      response both in MLR and in allogeneic islet transplantation model, indicating
      that single amino acid mutation does not affect the inhibitory function of CTLA
      4Ig. CTLA-4Ig-CTKC can be used in vehicle-mediated drug delivery system such as
      liposome conjugation.

PMID- 23559897
TI  - Ribavirin Does Not Impair the Suppressive Activity of Foxp3(+)CD4(+)CD25(+)
      Regulatory T Cells.
AB  - Ribavirin is an antiviral drug used in combination with pegylated interferon
      alpha (IFN-alpha) for the treatment of hepatitis C virus (HCV) infection.
      Recently, ribavirin was reported to inhibit the suppressive activity of
      regulatory T (Treg) cells. In the present study, we re-evaluated the effect of
      ribavirin on Foxp3(+)CD4(+)CD25(+) Treg cells from normal donors. First, we
      examined the expression of CTLA-4 and CD39, which are known to play a role in the
      suppressive function of Treg cells. We found that ribavirin treatment did not
      modulate the expression of CTLA-4 and CD39 in Treg cells. We also studied the
      effect of ribavirin on Treg cells in the presence of IFN-alpha; however, the
      expression of CTLA-4 and CD39 in Treg cells was not changed by ribavirin in the
      presence of IFN-alpha. Next, we directly evaluated the effect of ribavirin on the
      suppressive activity of Treg cells in the standard Treg suppression assay, by co
      culturing CFSE-labeled non-Treg CD4(+) T cells with purified Treg cells. We found
      that ribavirin did not attenuate the suppressive activity of Treg cells. Taken
      together, while ribavirin reversed Treg cell-mediated suppression of effector T
      cells in the previous study, we herein demonstrate that ribavirin does not impair
      the suppressive activity of Treg cells.

PMID- 23559898
TI  - Induction of Potent Antigen-specific Cytotoxic T Cell Response by PLGA
      nanoparticles Containing Antigen and TLR Agonist.
AB  - Previously we showed that biodegradable nanoparticles containing poly-IC or CpG
      oligodeoxynucleotide (ODN) together with ovalbumin (OVA) were efficient at
      inducing MHC-restricted presentation of OVA peptides in dendritic cells. The CTL
      inducing activities of the nanoparticles were examined in the present study.
      Nanoparticles containing poly-IC or CpG ODN together with OVA were prepared using
      biodegradable polymer poly(D,L-lactic acid-co-glycolic acid), and then were
      opsonized with mouse IgG. The nanoparticles were injected into the tail vein of
      mice, and 7 days later the OVA-specific CTL activities were measured using an in
      vivo CTL assay. Immunization of mice with the nanoparticles containing poly-IC or
      CpG ODN together with OVA elicited potent OVA-specific CTL activity compared to
      those containing OVA only. In accordance with these results, nanoparticles
      containing poly-IC or CpG ODN together with OVA exerted potent antitumor activity
      in mice that were subcutaneously implanted with EG7.OVA tumor cells. These
      results show that encapsulation of poly-IC or CpG ODN together with antigen in
      biodegradable nanoparticles is an effective approach for the induction of potent
      antigen-specific CTL responses in vivo.

PMID- 23559899
TI  - Modulation of Humoral and Cell-Mediated Immunity Against Avian Influenza and
      Newcastle Disease Vaccines by Oral Administration of Salmonella enterica Serovar
      Typhimurium Expressing Chicken Interleukin-18.
AB  - Interleukin-18 (IL-18) has been known to induce interferon-gamma (IFN-gamma)
      production and promote Th1 immunity. Although mammalian IL-18 has been
      characterized in great detail, the properties and application of chicken IL-18
      remain largely uninvestigated as of yet. In this study, we evaluated the
      immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing
      chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza
      (AI) and Newcastle disease (ND) vaccines. After oral administration of S.
      enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated
      intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine
      or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted
      using the same protocol 7 days later. Humoral and cell-mediated immune responses
      were evaluated in terms of HI antibody titers and proliferation and mRNA
      expression of IFN-gamma and IL-4 of peripheral blood mononuclear cells (PBMC) in
      response to specific antigen stimulation. According to our results, oral
      administration of S. enterica serovar Typhimurium expressing chIL-18 induced
      enhanced humoral and Th1-biased cell-mediated immunity against AI and ND
      vaccines, compared to that of chickens received S. enterica serovar Typhimurium
      harboring empty vector. Therefore, we conclude that our proposed vaccination
      regimen using inactivated AI and ND viruses along with oral administration of S.
      enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in
      protecting chicken from currently circulating AI and ND virus strains.

PMID- 23559900
TI  - Prevalence of Self-reported Cardiovascular Risk Factors among Saudi Physicians: A
      Comparative Study.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death worldwide.
      CVD-related mortality can be substantially reduced by modifying risk factors.
      METHODS: In this cross-sectional study conducted in King Abdulaziz Medical City,
      Riyadh, we estimated and compared prevalence of self-reported risk factors for
      CVD among physicians and a comparative group of non-physician health workers. We
      postulated that prevalence of CVD risk factors would be significantly lower in
      physicians. Participants filled in a structured self-administered questionnaire
      on CVD risk factors. RESULTS: The study included 200 participants (100
      respondents each group). Participants in the two groups were of similar age (P =
      0.46) and Body Mass Index (BMI) P = 0.11. There was no statistical difference in
      smoking, frequency and length of physical exercise per week (P = 0.53, 0.57, 0.47
      respectively). Diet habits showed daily intake of more protein, less fat and
      highly processed food, and similar vegetables, fruit and carbohydrate among
      physicians. Health status (presence of hypertension, diabetes, or dyslipidemia,
      or other diseases) didn't differ between the two groups. Physicians showed a
      significantly higher familial cardiovascular risk, with mothers and siblings
      having more dyslipidemia, but there was no significant difference in parental
      dyslipidemia, diabetes or hypertension. CONCLUSION: These findings indicate that
      high awareness of CVD and associated risk factors alone is not enough to prevent
      their occurrence. Programs to routinely screen these risk factors and improve the
      lifestyle of physicians are needed.

PMID- 23559901
TI  - Dosimetric Consistency of Co-60 Teletherapy Unit- a ten years Study.
AB  - OBJECTIVE: The goal of the Radiation standards and Dosimetry is to ensure that
      the output of the Teletherapy Unit is within +/-2% of the stated one and the
      output of the treatment dose calculation methods are within +/-5%. In the present
      paper, we studied the dosimetry of Cobalt-60 (Co-60) Teletherapy unit at Sher-I
      Kashmir Institute of Medical Sciences (SKIMS) for last 10 years. Radioactivity is
      the phenomenon of disintegration of unstable nuclides called radionuclides. Among
      these radionuclides, Cobalt-60, incorporated in Telecobalt Unit, is commonly used
      in therapeutic treatment of cancer. Cobalt-60 being unstable decays continuously
      into Ni-60 with half life of 5.27 years thereby resulting in the decrease in its
      activity, hence dose rate (output). It is, therefore, mandatory to measure the
      dose rate of the Cobalt-60 source regularly so that the patient receives the same
      dose every time as prescribed by the radiation oncologist. The under dosage may
      lead to unsatisfactory treatment of cancer and over dosage may cause radiation
      hazards. Our study emphasizes the consistency between actual output and output
      obtained using decay method. METHODOLOGY: The methodology involved in the present
      study is the calculations of actual dose rate of Co-60 Teletherapy Unit by two
      techniques i.e. Source to Surface Distance (SSD) and Source to Axis Distance
      (SAD), used for the External Beam Radiotherapy, of various cancers, using the
      standard methods. Thereby, a year wise comparison has been made between average
      actual dosimetric output (dose rate) and the average expected output values
      (obtained by using decay method for Co-60.). RESULTS: The present study shows
      that there is a consistency in the average output (dose rate) obtained by the
      actual dosimetry values and the expected output values obtained using decay
      method. The values obtained by actual dosimetry are within +/-2% of the expected
      values. CONCLUSION: The results thus obtained in a year wise comparison of
      average output by actual dosimetry done regularly as a part of Quality Assurance
      of the Telecobalt Radiotherapy Unit and its deviation from the expected output
      data is within the permissible limits. Thus our study shows a trend towards
      uniformity and a better dose delivery.

PMID- 23559902
TI  - Mast cell density in oral submucous fibrosis: a possible role in pathogenesis.
AB  - OBJECTIVE: Oral submucous fibrosis (OSMF) is a premalignant condition of oral
      cavity characterized by inflammation and progressive mucosal fibrosis. It has
      questionable pathogenesis. Mast cells (MC) have been associated with variety of
      inflammatory and fibrotic conditions, but little is known about their role in
      OSMF. Mast cells have been studied in normal gingiva, chronic inflammatory
      gingivitis, desquamative gingivitis, lichen planus, OSMF and oral cancer. Mast
      cells exhibit phenotypic plasticity. There is variation in the mast cell
      mediators with the change in the microenvironment, which makes the study of this
      cell in various diseases interesting. STUDY DESIGN: A retrospective study was
      conducted to find possible correlation between MC in 25 cases of OSF, 10 cases of
      oral squamous cell carcinoma (OSCC) and 10 cases of normal buccal mucosa by means
      of acidified toluidine blue staining method. RESULTS: The density of MC increased
      with disease progression. The densities of MC were significantly higher in OSMF
      than in normal buccal mucosa (p=0.001). The average numbers of MCs per square
      millimeter were 25, 49.50, 53.25 & 55.25 respectively. CONCLUSION: The results
      suggest that MC have a definite role in initiation and progression of OSMF.

PMID- 23559903
TI  - Growth plate changes associated with Hypothyroidism amongst the pre and postnatal
      rats.
AB  - OBJECTIVES: This study is intended to examine the effect of hypothyroidism and
      thyroxin replacement on axial and appendicular skeletal growth, growth plate
      thickness and to observe associated microscopic changes within the growth plates.
      METHODOLOGY: Experimental albino rats were developed with carbimazole and
      carbimazole plus thyroxin. Animals were administered with these drugs throughout
      pregnancy (prenatally) and for a period of six weeks, postnatally. At the end of
      the experiment the animals were sacrificed, measured and processed to demonstrate
      the bony and cartilaginous parts. Ulna and tibia of both sides were removed and
      processed for light microscopy and growth plate measurement. RESULTS: At the end
      of the experiment, reduction in the crown rump length was observed in the
      carbimazole treated animals. It was 8.77%, 13.26% and 7.25% in the prenatal, two
      weeks and six weeks age group animals respectively. In carbimazole plus thyroxin
      treated animals, this reduction was 3.22%, 2.94% and 3.42%, when compared to
      their age matched controls. Reduction in the thickness of the Epiphyseal growth
      plate (EGP) was 16.89% and 12.80% in the ulna of the two and six weeks age group
      and 18.06 % and 15.65% in the tibia of the these animals respectively. The
      carbimazole plus thyroxin treated animals showed an increase in the thickness of
      EGP as compared to their age-matched controls though the crown rump length of
      these animals was less than the controls. Prenatally treated hypothyroid rats
      showed disrupted growth plates without any well-formed microscopic zones.
      CONCLUSION: The results of this study showed that the pre and postnatally,
      carbimazole induced hypothyroidism and its replacement therapy affected the axial
      and appendicular skeletal growth. Proximal limb bones of the prenatally induced
      hypothyroid animals showed the greatest skeletal change in this study.

PMID- 23559904
TI  - Gauging Skills of Hospital Security Personnel: a Statistically-driven,
      Questionnaire-based Approach.
AB  - OBJECTIVES: This study aims to gauge the technical and soft skills of the
      hospital security personnel so as to enable prioritization of their training
      needs. METHODOLOGY: A cross sectional questionnaire based study was conducted in
      December 2011. Two separate predesigned and pretested questionnaires were used
      for gauging soft skills and technical skills of the security personnel. Extensive
      statistical analysis, including Multivariate Analysis (Pillai-Bartlett trace
      along with Multi-factorial ANOVA) and Post-hoc Tests (Bonferroni Test) was
      applied. RESULTS: The 143 participants performed better on the soft skills front
      with an average score of 6.43 and standard deviation of 1.40. The average
      technical skills score was 5.09 with a standard deviation of 1.44. The study
      avowed a need for formal hands on training with greater emphasis on technical
      skills. Multivariate analysis of the available data further helped in identifying
      20 security personnel who should be prioritized for soft skills training and a
      group of 36 security personnel who should receive maximum attention during
      technical skills training. CONCLUSION: This statistically driven approach can be
      used as a prototype by healthcare delivery institutions worldwide, after
      situation specific customizations, to identify the training needs of any category
      of healthcare staff.

PMID- 23559905
TI  - Effect of exercise training and anabolic androgenic steroids on hemodynamics,
      glycogen content, angiogenesis and apoptosis of cardiac muscle in adult male
      rats.
AB  - OBJECTIVES: To investigate the effects of exercise training and anabolic
      androgenic steroids (AAS) on hemodynamics, glycogen content, angiogenesis,
      apoptosis and histology of cardiac muscle. METHODS: Forty rats were divided into
      4 groups; control, steroid, exercise-trained and exercise-trained plus steroid
      groups. The exercise-trained and trained plus steroid groups, after one week of
      water adaptation, were exercised by jumping into water for 5 weeks. The steroid
      and trained plus steroid groups received nandrolone decanoate, for 5 weeks.
      Systolic blood pressure and heart rate (HR) were monitored weekly. Heart
      weight/body weight ratio (HW/BW ratio) were determined. Serum testosterone,
      vascular endothelial growth factor (VEGF), cardiac caspase-3 activity and
      glycogen content were measured. RESULTS: Compared with control, the steroid group
      had significantly higher blood pressure, HR, sympathetic nerve activity,
      testosterone level, HW/BW and cardiac caspase-3 activity. Histological
      examination revealed apoptotic changes and hypertrophy of cardiomyocytes. In
      exercise-trained group, cardiac glycogen, VEGF and testosterone levels were
      significantly higher while HR was significantly lower than control. HW/BW was
      more than control confirmed by hypertrophy of cardiomyocytes with angiogenesis on
      histological examination. Trained plus steroid group, had no change in HR, with
      higher blood pressure and HW/BW than control, cardiac glycogen and serum VEGF
      were higher than control but lower than exercise-trained group. Histological
      examination showed hypertrophy of cardiomyoctes with mild angiogenesis rather
      than apoptosis. CONCLUSION: When exercise is augmented with AAS, exercise
      associated cardiac benefits may not be fully gained with potential cardiac risk
      from AAS if used alone or combined with exercise.

PMID- 23559906
TI  - Clinical and histopathologic characteristics of skin malignancies in Qassim
      Region, Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVE: The present study was undertaken to assess the pattern
      of skin malignancies in Qassim region, Kingdom of Saudi Arabia. METHODS: Data of
      histopathological confirmed cases of skin malignancies were collected from all
      the referral hospitals of Qassim region during a period from January 2000 to July
      2009. RESULTS: Out of 94 cases majority (90.4%) were Saudis, and males (74.5%).
      The most common malignant skin lesion was BCC (58.5%) followed by SCC (18.1%) and
      MM (11.7%), respectively. Other malignancies seen were DFSP (4.3%), sebaceous
      carcinoma (2.1%) and skin secondaries from lung, lymphoma and stomach (4.3%). The
      most common site was face for BCC, trunk for SCC, and limbs for MM. The DFSP did
      not show any particular pattern. CONCLUSION: All major types of skin malignancies
      were seen with patterns similar to those reported from various other regions of
      Saudi Arabia and other countries except for Kaposi's sarcoma which was not
      encountered in our study.

PMID- 23559907
TI  - Penetrating keratoplasty for keratoconus: visual and graft survival outcomes.
AB  - OBJECTIVES: To evaluate the complications, and visual and graft survival outcomes
      in eyes that had undergone penetrating keratoplasty (PKP) for keratoconus.
      METHODOLOGY: This restrospective study includes 311 patients with keratoconus who
      had undergone PKP between January 1, 2001, and December 31, 2002, at King Khaled
      Eye Specialist Hospital. All patients were followed up postoperatively (maximum
      follow-up, 65.77 months). RESULTS: The mean age of patients with keratoconus at
      transplantation was 23.72 years. A preoperative best spectacle-corrected visual
      acuity (BSCVA) OF 20/40 or better was achieved in 13 eyes (4.2%). At a mean
      follow-up of 27 months, 212 eyes (68.2%) achieved a BSCVA of 20/40 or better.
      Postoperative visual acuity was significantly associated with preoperative visual
      acuity (P < 0.00). Only 6 eyes (1.9%) experienced graft failure, with a mean
      follow-up of 23.62 months. The graft rejection rate (6.8%) was a significant risk
      factor for failure (P = 0.00). Age, gender, corneal graft diameter, and
      intraoperative vitreous loss had no statistically significant effects on the PKP
      outcome (P> 0.05). Kaplan-Meier analysis revealed that the probabilities of graft
      survival were 99.8% at 1 year and 97.6% at 5 years after transplantation.
      CONCLUSION: Performing PKP in eyes with keratoconus is associated with good
      visual results and an excellent graft outcome.

PMID- 23559909
TI  - Thrombolysis in the age of Primary Percutaneous Coronary Intervention: Mini
      Review and Meta-analysis of Early PCI.
AB  - OBJECTIVE: Primary Percutaneous Coronary Intervention (PCI) is the treatment of
      choice for ST-segment Elevation Myocardial Infarction (STEMI) if performed within
      90 minutes from first medical contact. However, primary PCI is only available for
      less than 25% of patients with STEMI. Early PCI or Pharmaco-invasive strategy has
      evolved from facilitated PCI but with more delayed timing from thrombolysis to
      PCI. AIM: Assess the safety and effectiveness of Early PCI. PATIENTS AND METHOD:
      We reviewed the data of the available therapy options for patients with STEMI.
      Then we performed a meta-analysis for all randomized controlled trials of early
      PCI versus standard therapy. RESULTS: Five studies fulfilled our inclusion
      criteria. Our meta-analysis showed improved cardiovascular events with early PCI
      compared to standard therapy (odd ratio of 0.54; 95% Confidence interval 0.47
      0.7, p<0.001). There were no significant bleeding complications when doing early
      PCI 4 to 24 hours after successful thrombolysis. CONCLUSION: Early PCI should be
      done to all STEMI patients within 24 hours after successful thrombolysis.

PMID- 23559908
TI  - Cucurbitacins - a promising target for cancer therapy.
AB  - During the last decades a large number of cucurbitacins have been isolated from
      various plant species belonging to other plant families than Cucurbitaceae.
      Although the roots and the fruits of plant belong to these Cucurbitaceae species
      are very bitter, they have been used as folk medicines in some countries because
      of their wide spectrum of pharmacological activities such as anti-inflammation
      and anticancer effects. In the last ten years, cucurbitacins had been shown to
      inhibit proliferation and induced apoptosis utilizing a long array of in vitro
      and in vivo cancer cell models. Several molecular targets for cucurbitacins have
      been discovered, such as fibrous-actin, signal transducer and activator of
      transcription (STAT), cyclooxygenase-2, etc. This review aimed at elucidating the
      natural sources of some cucurbitacin compounds, their chemical structure and
      derivatives, physical properties, biological activities and mechanism by which
      they reduce the proliferation human cancer cells. This widens our armaments
      against a devastating disease that we are failing to face.

PMID- 23559911
TI  - Risk of antimicrobial misuse.

PMID- 23559910
TI  - Eccrine angiomatous hamartoma, with verrocous hemangioma-like features: A case
      report.
AB  - Eccrine angiomatous hamartoma (EAH) is a rare, benign cutaneous tumor. It is
      characterized by the proliferation of the eccrine gland elements that are closely
      associated with capillary proliferation. Patients usually present with a solitary
      nodule on the extremities that appeared at birth or during the prepubertal years.
      We report a rare case of EAH in a 13-year-old boy, with clinical features
      suggesting melanoma. Histologically, an EAH with changes resembling a verrucous
      hemangioma was noted.

PMID- 23559912
TI  - Systemic antibiotic therapy in periodontics.
AB  - Systemic antibiotics in conjunction with scaling and root planing (SRP), can
      offer an additional benefit over SRP alone in the treatment of periodontitis, in
      terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk
      of additional CAL loss. However, antibiotics are not innocuous drugs. Their use
      should be justified on the basis of a clearly established need and should not be
      substituted for adequate local treatment. The aim of this review is to discuss
      the rationale, proper selection, dosage and duration for antibiotic therapy so as
      to optimize the usefulness of drug therapy.

PMID- 23559913
TI  - Management of peri-implantitis.
AB  - Peri-implantitis is a site-specific infectious disease that causes an
      inflammatory process in soft tissues, and bone loss around an osseointegrated
      implant in function. The etiology of the implant infection is conditioned by the
      status of the tissue surrounding the implant, implant design, degree of
      roughness, external morphology, and excessive mechanical load. The microorganisms
      most commonly associated with implant failure are spirochetes and mobile forms of
      Gram-negative anaerobes, unless the origin is the result of simple mechanical
      overload. Diagnosis is based on changes of color in the gingiva, bleeding and
      probing depth of peri-implant pockets, suppuration, X-ray, and gradual loss of
      bone height around the tooth. Treatment will differ depending upon whether it is
      a case of peri-implant mucositis or peri-implantitis. The management of implant
      infection should be focused on the control of infection, the detoxification of
      the implant surface, and regeneration of the alveolar bone. This review article
      deals with the various treatment options in the management of peri-implantitis.
      The article also gives a brief description of the etiopathogenesis, clinical
      features, and diagnosis of peri-implantitis.

PMID- 23559914
TI  - Role of forensic odontologist in post mortem person identification.
AB  - The natural teeth are the most durable organs in the bodies of vertebrates, and
      humankind's understanding of their own past and evolution relies heavily upon
      remnant dental evidence found as fossils. The use of features unique to the human
      dentition as an aid to personal identification is widely accepted within the
      forensic field. Comparative dental identifications play a major role in
      identifying the victims of violence, disaster or other mass tragedies. The
      comparison of ante-mortem and postmortem dental records to determine human
      identity has long been established. Indeed, it is still a major identification
      method in criminal investigations, mass disasters, grossly decomposed or
      traumatized bodies, and in other situations where visual identification is
      neither possible nor desirable. This article has comprehensively described some
      of the methods, and additional factors aiding in postmortem person
      identification.

PMID- 23559915
TI  - Salivary immunoglobulin classes in Nigerian cigarette smokers: Indication for
      increased risk of oral diseases.
AB  - BACKGROUND: Cigarette smoking is a worldwide social epidemic and it is one of the
      main causes of preventable death and disability. Gingivitis, periodontitis,
      pocket depth, attachment loss, alveolar bone loss, and tooth loss are some of
      oral pathologies commonly found in cigarette smokers. The aim of this study was
      to explore, for the first time among Nigerians, the interplay between components
      of cigarette smoke and salivary levels of immunoglobulin classes so as to provide
      oral immunological based reasons for oral diseases in cigarette smokers.
      MATERIALS AND METHODS: In this case-control study, 5 mL of unstimulated saliva
      was collected in plain sample bottles from 24 active smokers who smoke at least 6
      sticks of cigarette per day and 21 sex and age-matched non-smokers who were
      apparently healthy. The samples were spun and supernatant stored at -20 degrees C
      until assayed. The immunoglobulin levels of the samples were estimated using
      enzyme-linked immunosorbent assay (ELISA). Student's t-test (unpaired) was used
      to determine significant differences between the two groups. P values less than
      0.05 was considered significant. RESULTS: No significant differences were
      observed in the mean salivary levels of IgG, IgA, and IgE. Only IgM was
      significantly lower in smokers compared with non-smokers (P = 0.038). The
      proportion of smokers with detectable level of salivary IgE was lower compared
      with controls. CONCLUSION: Our study showed that there is decreased salivary IgM
      in smokers. This observation suggests that reduced salivary immunoglobulin level
      of IgM might be involved in the pathogenesis of oral diseases in cigarette
      smokers.

PMID- 23559916
TI  - Anterior and middle superior alveolar nerve block for anesthesia of maxillary
      teeth using conventional syringe.
AB  - BACKGROUND: Dental procedures in the maxilla typically require multiple
      injections and may inadvertently anesthetize facial structures and affect the
      smile line. To minimize these inconveniences and reduce the number of total
      injections, a relatively new injection technique has been proposed for maxillary
      procedures, the anterior and middle superior alveolar (AMSA) nerve block, which
      achieves pulpal anesthesia from the central incisor to second premolar through
      palatal approach with a single injection. The purpose of this article is to
      provide background information on the anterior and middle superior alveolar nerve
      block and demonstrate its success rates of pulpal anesthesia using the
      conventional syringe. MATERIALS AND METHODS: Thirty Caucasian patients (16 men
      and 14 women) with an average age of 22 years-old, belonging to the School of
      Dentistry of Los Andes University, were selected. All the patients received an
      AMSA nerve block on one side of the maxilla using the conventional syringe, 1 ml
      of lidocaine 2% with epinephrine 1:100.000 was injected to all the patients.
      RESULTS: The AMSA nerve block obtained a 66% anesthetic success in the second
      premolar, 40% in the first premolar, 60% in the canine, 23.3% in the lateral
      incisor, and 16.7% in the central incisor. CONCLUSIONS: Because of the
      unpredictable anesthetic success of the experimental teeth and variable
      anesthesia duration, the technique is disadvantageous for clinical application as
      the first choice, counting with other techniques that have greater efficacy in
      the maxilla. Although, anesthetizing the teeth without numbing the facial muscles
      may be useful in restorative dentistry.

PMID- 23559917
TI  - Effect of dry heat and steam sterilization on load-deflection characteristics of
      beta-titanium wires: An in vitro study.
AB  - BACKGROUND: Sterilization techniques could affect the characteristics of
      orthodontic wires. The aim of the present study was to evaluate the effect of
      steam and dry heat sterilization techniques on load-deflection behavior of five
      types of beta-titanium alloy wires. MATERIALS AND METHODS: The samples consisted
      of 30 straight lengths of five types of beta-titanium alloy wires: Titanium
      Molybdenum Alloy (TMA) Low Friction (TMAL), TMA Low Friction Colored (HONE),
      Resolve (RES), BetaForce (BETA), and BETA CNA (CNA). Thirty wire segments were
      divided into three groups of 10. Group 1 was the control group and the group 2
      samples were sterilized by dry heat in an oven (60 minutes at 160 degrees C) and
      group 3 by steam in an autoclave (15 minutes at 121 degrees C). Then all the wire
      samples underwent a three-point bending test in a testing machine to evaluate
      load-deflection properties. Data was analyzed by repeated measures ANOVA and
      Scheffe's test (alpha = 0.05). RESULTS: The results showed that dry heat
      sterilization significantly increased force levels during both loading and
      unloading of CNA, BETA and RES and during loading of HONE (P < 0.05). Steam
      sterilization significantly increased force levels during both loading and
      unloading of BETA and during unloading of HONE (P < 0.05), with no effects on the
      load-deflection characteristics of TMAL, CNA and RES (P > 0.05). CONCLUSION: It
      appears dry heat sterilization increases stiffness of RES, BETA, CNA and HONE but
      autoclave sterilization did not have any effect on load-deflection
      characteristics of most of the beta-titanium wires tested, indicating that
      clinicians who want to provide maximum safety for their patients can autoclave
      TMAL, RES and CNA before applying them.

PMID- 23559918
TI  - Cytotoxicity evaluation of three resin-based sealers on an L929 cell line.
AB  - BACKGROUND: Endodontic sealers usually come in contact with adjacent tissues and
      their biocompatibility is key in a successful treatment. The purpose of this
      study was to assess the cytotoxicity of three resin-based sealers, namely AH
      Plus, EndoREZ, and Epiphany in set and fresh states on an L929 cell line.
      MATERIALS AND METHODS: In this in vitro experimental study, the materials were
      mixed according to the manufacturers' instructions, and were divided into two
      groups, fresh and set. The elutes of materials were prepared separately and were
      incubated with L929 fibroblasts for 1 hour, 24 hours, and 72 hours. Pulp Canal
      Sealer and Dulbecco's Modified Eagle Medium (DMEM) served as positive and
      negative controls respectively. Cell viability was evaluated by MTT assay ([3-4,5
      dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide succinate), after 1 hour,
      24 hours, and 72 hours. The data were analyzed by analysis of variance (ANOVA),
      and Tukey multiple comparison test. RESULTS: After 1 hour, fresh Epiphany and
      fresh AH Plus were significantly more cytotoxic than their set samples. No
      significant difference was perceived between cytotoxicity of fresh state of
      sealers and positive control, or between set state and negative control. After 24
      hours, both fresh and set samples of all materials were significantly more
      cytotoxic than the negative control group, and were less cytotoxic than the
      positive control group. After 72 hours, the fresh and set samples of all
      materials were as cytotoxic as the positive control group. At each time point, no
      significant difference was perceived among different materials in terms of cell
      viability. CONCLUSION: The observed differences among the cytotoxicity of AH
      Plus, EndoREZ, and Epiphany did not reach a significant level at comparable time
      points after exposure.

PMID- 23559919
TI  - Comparison of bone regeneration using three demineralized freeze-dried bone
      allografts: A histological and histomorphometric study in rabbit calvaria.
AB  - BACKGROUND: It has been stated that the bone allografts from different tissue
      banks may lead to various amount of bone induction, so the aim of this study was
      to evaluate bone regeneration of three demineralized allografts both
      histologically and histomorphometrically in rabbits calvaria bone defects.
      MATERIALS AND METHODS: In this double-blind randomized experimental animal study,
      32 critical size defects (11-mm diameter) in the calvaria of 16 male New Zealand
      white rabbits were randomly filled with three demineralized freeze-dried bone
      allografts (DBM, CENOBONE, DEMBONE), while the nongrafted defect was regarded as
      control group. After 6 and 12 weeks of healing, the experimental animals were
      euthanized for specimen preparation. After histological evaluation,
      histomorphometric analysis was performed to quantify new bone formation and
      remained graft particles. The data were analyzed by one-way ANOVA with Tukey's ad
      hoc test and t-test. (P < 0.05 was considered to be statistically significant).
      RESULTS: Mean percentage of bone formation increased between two healing time,
      but it was not statistically significant in all groups except DBM which the bone
      formation significantly decreased (P = 0.04). There were not statistically
      significant differences between three allografts in remained particles and bone
      formation in both healing times and they could not induce significantly more bone
      formation than control group. CONCLUSION: Both test and control groups resulted
      in successful new bone formation. No difference was noted in bone formation and
      remained particles between three commercial bone allografts. Further studies in
      this issue may be needed.

PMID- 23559921
TI  - Surface discoloration of composite resins: Effects of staining and bleaching.
AB  - BACKGROUND: The purpose of this in vitro study was to evaluate surface
      discoloration of three microhybrid composite resins (Esthet*X HD, Clearfil AP-X,
      Gradia Direct) and five nanohybrid composite resins (Ceram*X, GC Kalore, G
      aenial, Grandio, GrandioSO), after staining and bleaching procedures. MATERIALS
      AND METHODS: The composite resins were polymerized with a curing light (Celalux
      II, Voco, Cuxhaven, Germany) into 160 silicon molds (6,4 mm in diameter and 2 mm
      in thickness) to obtain identical specimens. Twenty samples for each composite
      resin were prepared. The specimens were polished using an automated polishing
      machine with the sequence of 600-, 800-, 1000-grit abrasive paper under water
      irrigation. The specimens were immersed in tea and distilled water: the specimens
      were dipped for 20 min, once a day (every 24 h), for 14 days into the drinks. The
      specimens were then bleached with carbamide peroxide at 17% (Perfect Bleach
      Voco). The color of specimens was measured with a spectrophotometer according to
      the CIE L(*)a(*)b(*) system after light-polymerization of composite resin
      specimens, after 7 days, after 14 days, and after bleaching. The color difference
      h index (DEab(*)) between each measurement was calculated. Statistical analysis
      was made using analysis of variance (ANOVA). RESULTS: All specimens showed a
      significant increase in staining with a similar trend and no significant
      differences between microhybrid and nanohybrid composite resins. After whitening
      procedures, materials tested showed both significant and unsignificant
      differences of the h index. CONCLUSIONS: Microhybrid and nanohybrid composite
      resins had similar in vitro surface discoloration in tea. After bleaching,
      discoloration was removed from some composite resins tested.

PMID- 23559920
TI  - Knowledge and attitude of pediatricians and Family Physicians in Chennai on
      Pediatric Dentistry: A survey.
AB  - BACKGROUND: The aim of this study was to study the knowledge and attitude of the
      pediatricians and family physicians on the dental counterpart, i.e. pediatric
      dentistry and the objective of this study were to determine what can improve the
      knowledge and attitude on pediatric dentistry and suggest certain methodologies
      to more participation of physicians in improving oral health. MATERIALS AND
      METHODS: A systematic random survey of 400 pediatricians and 400 family
      physicians received a questionnaire pertaining to individual details, approach
      towards pediatric dentistry, knowledge level and the training on oral health
      received. RESULTS: Most of pediatricians and family physicians acknowledged the
      importance of pediatric dentistry. Less of pediatricians and more of family
      physicians predicted the parents may pose a barrier for referral. More number of
      pediatricians were aware of the oral benefits of breast feeding when compared to
      the family physician. Most of the practitioners in both groups were less aware of
      the first dental visit including ECC. Acknowledgement of the role in cleft lip
      and palate was more or less same in both groups of practitioners were as the
      effect of systemic disease on oral health was recognized by more number of
      pediatricians. Only a small percentage in both the groups acknowledged the
      cariogenicity of medicated syrups, which was substantiated by the fact that only
      a small number of physicians underwent dental training and most of them were
      accepting to undergo training. CONCLUSION: When basic medical training is
      provided in dental school, medical schools can also provide dental training.
      Dental lectures can also be incorporated into CME programs and recognition of
      pediatric dentistry by providing referral to needy patients have been suggested.

PMID- 23559922
TI  - Histological and histomorphometric analysis of animal experimental dehiscence
      defect treated with three bio absorbable GTR collagen membrane.
AB  - BACKGROUND: Guided tissue regeneration (GTR) allows mesenchymal cells to
      repopulate the defects. However, there is limited information regarding the
      efficacy of different membranes. The present study was designed to histologically
      and histomorphometrically compare three collagen membranes in regenerative
      treatment of dehiscence defects in dogs. MATERIALS AND METHODS: This 8 weeks
      experimental animal study comprised 4 healthy dogs. 5 * 5 mm periodontal
      dehiscences were created in each side of the mandible (4 dehiscences in each side
      of dogs' mandible). In each side, one dehiscence defect was left uncovered as a
      control site and three other sites were randomly covered with different collagen
      membranes (Biogide (BG), Biomend (BM), and Cytoplast (CYT)). Histomorphometric
      and histologic analysis were conducted at 4 and 8 weeks. Data were analyzed using
      ANOVA, Mann-Withney, Kruskal-Wallis and Fisher 's exact tests (alpha = 0.05).
      RESULTS: According to histomorphometric analysis there was a significant
      difference between treatment and control groups regarding the bone formation and
      the distance between the reference point and apical end of junctional epithelium
      (DJE) (P < 0.05). At 4 weeks, the maximum amount of bone thickness and height was
      observed in BG and CYT respectively, and this maximum rate was seen with the use
      of BG at 8 weeks. It was shown that DJE reached its highest rate in BM and CYT at
      4 and 8 weeks, respectively. Organized PDL was formed in treatment groups.
      CONCLUSION: The membrane-treated groups had a statistically significant increase
      in bone formation and connective tissue attachment compared to control groups.
      However, there are some differences among experimental groups, which should be
      considered in GTR treatments.

PMID- 23559924
TI  - A randomized clinical trial evaluating the success rate of ethanol wet bonding
      technique and two adhesives.
AB  - BACKGROUND: Composite resin restorations may have a short lifespan due to the
      degradation of resin-dentin interface. Ethanol wet bonding technique may extend
      the longevity of resin-dentin bond. The purpose of this one year randomized
      clinical trial was to compare clinical performance of two adhesives with ethanol
      wet bonding technique. MATERIALS AND METHODS: This randomized clinical trial was
      performed on 36 non-carious cervical lesions in 12 patients restored with
      composite resin using one of the following approaches: 1. OptiBond FL (Kerr,
      USA); 2. Clearfil SE Bond (Kuraray, Japan) with enamel etching and 3. Ethanol wet
      bonding technique with the part of adhesive of OptiBond FL. The clinical success
      rate was assessed after 24 h, 6, 9 and 12 months according to the United States
      Public Health Service (USPHS) criteria: Marginal discoloration, marginal defect,
      retention rate, caries occurrence, and postoperative sensitivity. The tooth
      vitality was also assessed. RESULTS: The retention rate was 100% at baseline and
      at 6 months follow up for all types of bonding protocols and was 91.67% at 9 and
      12 months follow up for ethanol wet bonding group. None of the restorations in
      three groups showed marginal defects, marginal discoloration or caries occurrence
      and were vital after 12 months. There was no statistically significant difference
      between three groups after 12 months follow up (p value = 0.358). CONCLUSIONS:
      Composite restorations placed using ethanol wet bonding technique presented equal
      performance to the other groups.

PMID- 23559923
TI  - The effect of vitamin D supplementation on bone formation around titanium
      implants in diabetic rats.
AB  - BACKGROUND: Diabetes has become the next most widespread disease after cancer.
      Recent studies have found that diabetes and moderate to severe vitamin D
      deficiency are associated with reduced bone mineral content; therefore
      administration of vitamin D may correct these conditions. The purpose of this
      research is to compare the effect of vitamin D administration on bone to implant
      contact in diabetic rats with control group. MATERIALS AND METHODS: In this
      randomized placebo-controlled trial, 48 Wistar rats were rendered diabetic (130<=
      blood sugar <=200 mg/dl) by IV injection of 35 mg/kg Alloxan. Implants were
      inserted in tibial bone; Then rats were divided into study and control groups and
      received oral vitamin D3 (160 IU) or placebo respectively for one week. Bone to
      implant contact value was measured under light microscope at 3 and 6 weeks.
      RESULTS: Analysis of data indicated that vitamin D had no significant effect on
      bone to implant contact (BIC). At 3 weeks, the control group (n = 5) reported BIC
      level at 44 +/- 19 and study group (n = 7) at 57 +/- 20. At 6 weeks, the control
      group (n = 5) reported BIC level at 70 +/- 29, and study group (n = 10) at 65 +/-
      22. Twenty one samples were missed because of death or incorrect lab processes.
      CONCLUSION: It seems that vitamin D supplement has no significant effect on BIC
      in 130 mg/dL <= blood sugar <=200 mg/dL (P = 0.703) andwas also not time
      dependent (P = 0.074).

PMID- 23559925
TI  - Effect of phosphate-buffered saline on push-out bond strength of a new bioceramic
      sealer to root canal dentin.
AB  - BACKGROUND: The aim of this study was to compare push-out bond strength of a new
      bioceramic endodontic sealer, EndoSequence BC sealer (Brasseler USA, Savannah,
      GA), used with gutta-percha in the presence or absence of phosphate-buffered
      saline solution (PBS) within the root canals. MATERIALS AND METHODS: Forty single
      rooted human teeth were prepared and randomly divided into four groups. Samples
      in groups 1 and 2 were dried, but those in groups 3 and 4 were moistened with PBS
      before obturation. All root canals were obturated with gutta-percha/EndoSequence
      BC sealer. The specimens were stored in PBS for 7 days in groups 1 and 3 and for
      2 months in groups 2 and 4. Push-out bond strength values and failure modes were
      evaluated. The data on push-out bond strength were analyzed using two-way ANOVA.
      RESULTS: The mean value for the bond strength of the obturation material in
      moistened canals was significantly higher than that in dried ones at 1 week (P =
      0.00). Contrarily, there was no significant difference between dried and
      moistened root canals at 2 months (P = 0.61). In dried canals, bond strength
      increased significantly with time but in moistened ones, the difference was not
      significant. Inspection of the specimens revealed the bond failure to be mainly
      cohesive for all groups. CONCLUSION: The presence of PBS within the root canals
      increased the bond strength of EndoSequence BC sealer/gutta-percha at 1 week.
      However, no difference was found between the bond strength of EndoSequence BC
      sealer/gutta-percha in the presence or absence of PBS in the root canals at 2
      months.

PMID- 23559926
TI  - Evaluation of dental socket healing after using of porous titanium granules:
      Histologic and histomorphometric assessment in dogs.
AB  - BACKGROUND: Different methods have been suggested to preserve bone architecture
      following traumatic events such as teeth extraction. The purpose of the study was
      to histologically and histomorphometrically evaluate the dental socket healing
      after applying porous titanium granules (PTG) in dogs. MATERIALS AND METHODS:
      Four healthy male dogs were involved in the present 6-weeks experimental animal
      study. Three sockets were surgically created in each side of dog's mandible. One
      of the sockets in one side was randomly filled by PTG and covered by a resorbable
      membrane (Tigran + membrane group). Another socket was left unfilled and just
      covered by the same membrane (membrane group) and the last one was left unfilled
      and uncovered as the control group. The dogs were killed at two time intervals (2
      weeks and 6 weeks, two dogs at each time point). All samples were histologically
      evaluated under an optical microscope for a new bone formation. Data were
      analyzed by SPSS ver. 16 and Kruskal-Wallis and Mann-Whitney tests were used to
      compare data in different groups (alpha = 0.05). RESULTS: There was a significant
      difference between the Tigran + membrane and the control group in 2 and 6 weeks
      in the mean amount of total regenerated bone (P < 0.05). The mean amounts of
      woven, lamellar, and total regenerated bone showed significant differences
      between 2 weeks and 6 weeks for all three groups (P < 0.05). CONCLUSIONS: It can
      be assumed that the use of Tigran bone substitute with membrane can promote the
      bone regeneration in bone defects.

PMID- 23559927
TI  - Assessing joint space and condylar position in the people with normal function of
      temporomandibular joint with cone-beam computed tomography.
AB  - BACKGROUND: The optimal position of the condyle in glenoid fossa is a fundamental
      question in dentistry. There is no quantitative standard for the optimal position
      of mandibular condyle in the glenoid fossa in our population. The purpose of this
      study is to assess the position of the condyle by cone beam computed tomography
      (CBCT) images in patient with normal function of temporomandibular joint (TMJ).
      MATERIALS AND METHODS: In this cross-sectional study, CBCT images of 40 class I
      skeletal patients (15 males and 25 females) without history of TMJ disorders were
      selected. Next, the anterior, superior and posterior joint spaces (Ajs, Sjs, Pjs)
      were measured on the two true central sagittal slices. Then medial (M) and
      lateral (L) joint spaces on true coronal view were measured in the right and left
      sides, separately. After that, P/A ratio, S/A ratio and M/L ratio were
      calculated. Finally, a paired t-test and independent samples t-test were employed
      for analysis. RESULTS: The centric position of the condyle in glenoid fossa was
      more common (92.5%) than other positions. Significant differences in Ajs, Sjs,
      Pjs, Mjs and Ljs values between two sides were observed (P <= 0.05).
      Additionally, Sjs showed statistically significant differences between the sexes
      (P = 0.05). P/A ratio and S/A ratio had significant differences between two sides
      but not between those sexes. CONCLUSION: The assessment of joint spaces in right
      and left sides should be done independently. Overall, the measured joint spaces
      except Sjs are not different in two sexes. The data from this study could be a
      useful and comparable reference for the clinical assessment of condylar position
      in patients with normal functional joints.

PMID- 23559928
TI  - Comparison of the bactericidal efficacy of photodynamic therapy, 2.5% sodium
      hypochlorite, and 2% chlorhexidine against Enterococcous faecalis in root canals;
      an in vitro study.
AB  - BACKGROUND: Enterococcus faecalis has been widely used as a valuable
      microbiological pathogen for in vitro studies due to its ability to successfully
      colonize the root canal in a biofilm-like style, invade dentinal tubules, and
      resist endodontic treatment procedures.The aim of this study was to compare the
      bactericidal efficacy of photodynamic therapy (PDT), 2% chlorhexidine, 2.5%
      NaOCl, and combination of PDT and 2.5% NaOCl against E. faecalis. MATERIALS AND
      METHODS: Sixty single-rooted teeth had their canals contaminated with E. faecalis
      in brain heart infusion broth and were incubated for 48 hours.The canals were
      then subjected to 2% chlorhexidine, 2.5% NaOCl, PDT (red light emitting diode 625
      nm+ Toludine Blue) and PDT + 2.5% NaOCl. Controls consisted of no treatment
      (positive control) and without inoculation of bacterium (negative control).
      Following treatment, the canal contents were sampled with sterile paper
      points.The samples were dispersed in transport medium, serially diluted, and
      cultured on blood agar to determine the number of colony forming units (CFU).
      Data were analyzed by Mann-Whitney U test at 5% significance level. The
      significance level for all analyses was set at P <.05. RESULTS: Combination of
      PDT and 2.5% NaOCl achieved maximum reduction in recovered viable bacteria, no
      viable bacteria was observed after treatment of PDT + 2.5% NaOCl. CONCLUSION:
      Combination of PDT and 2.5% NaOCl simultaneously is effective in the elimination
      of E. faecalis from dentinal tubules under the conditions of this study.

PMID- 23559929
TI  - Study of occlusal characteristics of primary dentition and the prevalence of
      maloclusion in 4 to 6 years old children in India.
AB  - BACKGROUND: To assess the prevalence of malocclusion and to determine the
      different occlusal characteristics in primary dentition of 4 to 6 years old
      children in India. MATERIALS AND METHODS: The target population comprised 4 to 6
      years old children attending different nursery, kindergarten and primary schools
      of Bagalkot city. Stratified cluster random sampling procedure was executed to
      collect the representative sample. Each subject was assessed for various occlusal
      characteristics. RESULTS: Occlusal characteristic found were flush terminal plane
      (52.5%), class I canine relationship (84%), maxillary developmental spaces
      (35.4%), primate spaces in maxilla (47.6%), mandibular crowding (4.6%),
      mandibular midline shift (5.6%), anterior multiple tooth crossbite (1.3%),
      scissors bite (0.6%), anterior open bite (1%), over bite of 0-2 mm (81.6%) and
      overjet of 0-2 mm (84.5%). The age wise difference for the occlusal
      characteristics was statistically significant. CONCLUSIONS: The data revealed
      that most of the children had malocclusion. This highlights the importance of
      identifying children who are in need of orthodontic treatment for dental health
      or aesthetic reasons.

PMID- 23559930
TI  - Evaluation of factors influencing child abuse leading to oro-facial lesions in
      Isfahan, Iran: A qualitative approach.
AB  - BACKGROUND: Since child abuse and neglect are serious conditions which can
      potentially lead to inappropriate dental health, we conducted this qualitative
      study to define the factors influencing child abuse and neglect, which lead to
      oro-facial lesions. MATERIALS AND METHODS: Qualitative semi-structured interviews
      were conducted by social services employees. Purposive sampling was used to
      recruit participants to capture a range of experiences such as the physical
      abuse, sexual abuse, role of family in child abuse, age, and gender. RESULTS:
      Participants demonstrated a range of perceptions which lead to child abuse
      including hitting on the head and slapping. Often subsidiary to this view,
      several factors were mentioned that occasionally influenced child abuse. These
      factors appeared to be idiosyncratic but could be drawn together into three
      categories: Cultural lacks which includes poverty, cruelty of parents and
      addiction, psychological disorders, and separation in the family which was seen
      in most of the children. CONCLUSION: This study has identified a variety of
      factors influencing the incidence of child abuse. Therefore, dentists should
      meticulously pay attention to children who have these risk factors in order to
      discover child abuse events. Quantitative research would reveal the extent of
      these factors. Dentists' knowledge of their roles in managing cases suffering
      from abuse might need to be assessed to see if dentists need further education in
      this important area.

PMID- 23559931
TI  - Comparison of shear bond strength of two veneering ceramics to zirconia.
AB  - BACKGROUND: Chip-off fracture of veneering porcelain has been described as the
      most frequent reason for the failure of zirconia-based fixed partial dentures.
      The purpose of this study was to evaluate the shear bond strength (SBS) of two
      commercial zirconia core ceramics to their corresponding veneering ceramics.
      MATERIALS AND METHODS: Zirconia disks with 7-mm diameter and 3-mm height were
      prepared (Cercon and Biodenta systems) and veneered with recommended layering
      ceramics (Cercon ceram and 2 in 1 ceramic, respectively) (n = 10). The disks were
      polished with diamond paste and airborne-particle abraded before layering. The
      specimens were mounted in a T-shaped metal holder using autopolymerized acrylic
      resin and stored in 37 degrees C distilled water for one week, after which they
      were subjected to thermal cycling. SBS of zirconia core to veneering ceramic was
      measured using a universal testing machine and failure modes were determined
      microscopically. Data were analyzed using t test (alpha < 0.05). RESULTS: Mean
      (+/-SD) SBS values were 27.19(+/-3.43) and 28.22(+/-4.08) MPa for Cercon and
      Biodenta systems, respectively, with no significant difference. Biodenta system
      showed more adhesive failure compared to more combined (adhesive and cohesive)
      failures in Cercon system. CONCLUSION: Within the limitations of this study it
      can be concluded that SBS of Biodenta and Cercon specimens were nearly the same,
      but the fracture mode of these two systems were different. Since Biodenta
      fracture pattern was predominantly adhesive, it seems that maybe Biodenta
      porcelain was stronger than Cercon porcelain where as its adhesive bond was
      weaker.

PMID- 23559932
TI  - Periodontal disease as the initial oral manifestation of abdominal tuberculosis.
AB  - Tuberculosis is a chronic, specific granulomatous disease and a major cause of
      death in developing countries. We report a case of tuberculosis presenting first
      as periodontal loss of tooth support leading to loose teeth and gingival
      enlargement affecting a 17-year-old female patient without any pulmonary lesion.
      Diagnosis was based on histopathological examination and positive adenosine
      deaminase activity Mycobacterium tuberculosis test. The clinical presentation of
      tuberculosis may take many forms. However, with the decline in numbers,
      tuberculosis lesions of the oral cavity have become so rare that they are
      frequently overlooked in the differential diagnosis of oral lesions. Also, this
      case report emphasizes the need for dental clinicians to be aware of the
      possibility of tuberculosis presenting first in the oral cavity, and contribute
      in control of tuberculosis through early detection and referring the patients to
      physicians for proper treatment.

PMID- 23559933
TI  - The reverse claw: Report of an extremely rare facial talon cusp.
AB  - Talon cusp is a rare developmental anomaly that occurs most commonly on the
      lingual side of the incisors. Occurrence of the labial talon cusp is rare in the
      dental literature. Till date only seven cases of isolated nonsyndromic labial
      talon cusps have been reported in the maxillary permanent dentition. However, a
      few cases of syndromic labial talon cusps and faciolingual talon cusps have been
      reported. The aim of our report is to highlight clinical and radiological
      features of this rare anomaly.

PMID- 23559935
TI  - Eruption cysts: A series of two cases.
AB  - Eruption cysts are benign cysts that appear on the mucosa of a tooth shortly
      before its eruption. They may disappear by themselves but if they hurt, bleed or
      are infected they may require surgical treatment to expose the tooth and drain
      the contents. Here we present 2 case reports of eruption cysts presenting with
      different chief complaint. The treatment included incising the eruption cyst and
      draining the contents of the cyst.

PMID- 23559934
TI  - Adenoid cystic carcinoma of the buccal mucosa: A case report and review of the
      literature.
AB  - Adenoid cystic carcinomas are deceptive malignancies that show slow growth and
      local invasion with recurrences seen many years after diagnosis. Upto 50% of
      these tumors occur in the intraoral minor salivary glands usually in the hard
      palate. Buccal mucosal tumors are relatively rare. We determined the incidence of
      buccal mucosal adenoid cystic carcinoma by reviewing the number of reported cases
      in the literature. This is the first article to analyze the occurrence of adenoid
      cystic carcinomas in the buccal mucosa through a review of 41 articles. Our
      review revealed 178 buccal mucosal adenoid cystic carcinomas among a total of
      2,280 reported cases. We present a case of adenoid cystic carcinoma occurring in
      the left buccal mucosa of a 45-year-old female.

PMID- 23559936
TI  - Infantile hemiplegia in pediatric dental set-up.
AB  - Infantile hemiplegia refers to brain injuries that occur before or at birth and
      lead to hemiplegia/ total paralysis of one side of the body, including the face,
      arm and leg. The main purpose of this article is to provide valuable information
      to pediatric dentists about the review and treatment alternatives for patients
      with infantile hemiplegia. This article reports the case of a 12-year-old girl
      with a hemiplegia of left side of the body suffering with tooth ache and gum
      inflammation. The treatment performed was rehabilitation with oral prophylaxis
      and extractions of root stumps followed by thorough preventive regimen with
      periodic check-ups.

PMID- 23559937
TI  - Resveratrol as a supplemental treatment for periodontitis.

PMID- 23559938
TI  - Mouth: A portal to the body.
AB  - Periodontal disease is now increasingly believed to play a significant part in
      various systemic conditions. Likewise these systemic diseases and their severity
      have been found to have an impact on the morbidity of periodontal disease. A
      number of mechanisms specific to such interlink have been proposed and later
      established in numerous studies. The disorders with such bidirectional link with
      periodontal disease include cardiovascular, respiratory, neurological, and
      connective tissue diseases. The periodontal - systemic interlink has a vibrant
      effect on the management aspects and is of paramount topical interest to
      clinicians. We review the pertaining literature (Google scholar and pubmed).

PMID- 23559939
TI  - Clinical audit in dentistry: From a concept to an initiation.
AB  - Clinical audit is a quality improvement process that aims to improve patient care
      through a systematic review of care against explicit criteria. It is a cyclic and
      multidisciplinary process which involves a series of steps from planning the
      audit through measuring the performance to implementing and sustaining the
      change. Although audit contains some facets of research, it is essential to
      understand the difference between the two. Auditing can be done right from the
      record maintaining, diagnosis and treatment and postoperative evaluation and
      follow-up. The immense potential of clinical audit can be utilized only when open
      mindedness and innovativeness are encouraged and evidence-based work culture is
      cultivated.

PMID- 23559940
TI  - Tissue engineering in periodontal regeneration: A brief review.
AB  - Periodontal disease is a major public health issue and the development of
      effective therapies to treat the disease and regenerate periodontal tissue is an
      important goal of today's medicine. Regeneration of periodontal tissue is perhaps
      one of the most complex process to occur in the body. Langer and colleagues
      proposed tissue engineering as a possible technique for regenerating the lost
      periodontal tissues. Tissue engineering is a multidisciplinary field, which
      involves the application of the principles and methods of engineering and life
      sciences to help in the development of biological substitutes to restore,
      maintain or improve the function of damaged tissues and organs. A Google/Medline
      search was conducted and relevant literature evaluating the potential role of the
      tissue engineering in periodontal regeneration, which included histological
      studies and controlled clinical trials, was reviewed. A comprehensive search was
      designed. The articles were independently screened for eligibility. Articles with
      authentic controls and proper randomization and pertaining specifically to their
      role in periodontal regeneration were included. The available literature was
      analyzed and compiled. The analysis indicate tissue engineering to be a
      promising, as well as an effective novel approach to reconstruct and engineer the
      periodontal apparatus. Here, we represent several articles, as well as recent
      texts that make up a special and an in-depth review on the subject. The purpose
      behind writing this brief review has been to integrate the evidence of research
      related to tissue engineering so as to implement them in our daily practice.

PMID- 23559941
TI  - Dental caries in relation to socio-behavioral factors of 6-year-old school
      children of Udaipur district, India.
AB  - BACKGROUND: Based on the previous national oral health survey in India, some
      variation was observed in oral health status and behavior between the urban and
      rural population. Thus, the present study aimed to assess the dental caries
      experience in deciduous dentition of 6-year-old urban and rural schoolchildren of
      Udaipur district and to evaluate the influence of socio behavioral
      characteristics on dental caries experience. MATERIALS AND METHODS: A combination
      of multi stage and cluster sampling procedure was executed to collect a
      representative sample of 875, 6-year-old school children. Clinical examination
      for caries was conducted using dmft (decayed, missing and filled teeth) index.
      Socio - demographic information was collected prior to clinical examination in
      addition to information on oral health behavior by personal interviews. RESULTS:
      Only 7.8% children reported of brushing their teeth twice or more than twice
      daily. Rural children visited the dentist less often than the urban children (P <
      0.05). Greater proportion of boys (62.2%) experienced caries than girls (55.1%),
      decayed component constituted a major contribution for dmft. Multivariate
      analysis demonstrated the influence of gender, urbanization, tooth brushing
      frequency, dental visits, parent's education and occupation on caries occurrence.
      CONCLUSIONS: Rural children and boys experienced greater caries than their urban
      and girl counterparts. Caries experience was related to the parent's occupation
      and education. Moreover, caries occurrence was influenced by brushing frequency
      and dental visiting habits.

PMID- 23559942
TI  - Microbiological analysis of oral samples for detection of Mycobacterium
      tuberculosis by nested polymerase chain reaction in tuberculosis patients with
      periodontitis.
AB  - BACKGROUND: Due to high prevalence of tuberculosis (TB) in India, presence of
      Mycobacterium tuberculosis in oral samples might influence the periodontal status
      of patients and also might pose a risk of transmission of TB during dental
      procedures through aerosols. Hence, this study aims to compare the periodontal
      status between TB and non-TB patients and to detect the presence of M.
      tuberculosis in plaque and saliva of TB and non-TB patients. MATERIALS AND
      METHODS: A total of 25 TB and 25 non-TB systemically healthy patients (age 21-49
      years) were selected for this Clinico-Microbiological study. The oral hygiene and
      periodontal status of the patients were measured by using clinical indices and
      were compared using Mann-Whitney test (P < 0.05 = Significant). Pooled plaque and
      unstimulated salivary samples were collected and subjected to microbiological
      evaluation of M. tuberculosis by nested polymerase chain reaction. The detection
      rates were compared using Chi-square test (P < 0.001 = Highly significant).
      RESULTS: No significant difference was observed in periodontal clinical
      parameters measured between the groups. M. tuberculosis was detected in 92% of
      saliva and 68% of plaque samples of tuberculosis group, and even in 12% of saliva
      samples in nontuberculosis group patients. CONCLUSION: The TB status of the
      patient did not influence the periodontal status. However, the presence of M.
      tuberculosis in plaque and saliva as detected in this study might pose a grave
      risk of transmission of the disease through aerosols during dental procedures.

PMID- 23559943
TI  - Histologic evaluation of chitosan as an accelerator of bone regeneration in
      microdrilled rat tibias.
AB  - BACKGROUND: Chitosan compounds have been shown to be suitable bone replacement
      materials. To evaluate the accelerating effects of chitosan on the bone
      regeneration process and assessing its histopathological adverse effects, we
      conducted this study on rat tibias. MATERIALS AND METHODS: In a laboratory
      experimental study, micro-drilled bone defects were created in the upper tibia of
      each leg in 15 adult male rats. The defect in the right leg, filled by the
      chitosan powder, was compared with the untreated defect in the left leg in each
      rat at 1, 2, and 4 weeks after surgery. Bone repair and inflammation in each
      specimen was blindly graded by a pathologist. Reaction to the foreign body and
      the amount of the remaining chitosan were studied in chitosan-treated specimens
      at the three stages of the study. RESULTS: Bone repair was significantly faster
      in the chitosan group, 1 week (P = 0.01) and 4 weeks (P = 0.038) after surgery,
      while the difference was not significant at the 2-week stage (P = 0.197) between
      chitosan and control groups. Chitosan-induced inflammation was not significant in
      any stage of the study. Reaction to the foreign body was seen in one case at 2
      weeks and one case at 4 weeks postoperation. CONCLUSION: Chitosan significantly
      accelerated the bone regeneration process in rat tibias. Regarding its
      biocompatibility and osteoinductivity, it can be studied as a biomaterial in
      human bone healing.

PMID- 23559944
TI  - Effects of surface treatments of conventional glass-ionomer on shear bond
      strength to giomer.
AB  - BACKGROUND: An appropriate bond between glass-ionomer and the superficial resin
      materials is very important for the success of sandwich technique. The aim of the
      present in vitro study was to evaluate the effect of three surface treatments of
      conventional glass-ionomer on its shear bond strength to giomer. MATERIALS AND
      METHODS: Sixty cylindrical specimens of a conventional glass-ionomer (GC Fuji II)
      were prepared and randomly divided into three groups (n = 20). The specimens in
      groups 1 and 2 were treated with total-etch adhesive resin (Single Bond) along
      with acid etching, and self-etch adhesive resin (FL-Bond II) on the set glass
      ionomer, respectively. Specimens in group 3 were treated with self-etch adhesive
      resin (FL-Bond II) before initial setting of the glass-ionomer was complete. Then
      a giomer restorative (Beautifil II) was added to the specimens. Subsequent to
      thermocycling, the specimens were subjected to shear bond strength test. Failure
      modes were evaluated under a stereomicroscope. Data were analyzed by one-way
      analysis of variance and a post hoc Tukey test at a significance level of P <
      0.05. RESULTS: There were statistically significant differences in bond strengths
      between the groups (P < 0.0005). Differences in bond strengths between group 2
      and other groups were significant (P < 0.0005) while the differences between
      groups 1 and 3 were not significant. Failures were predominantly of the cohesive
      type in all the groups. CONCLUSION: Based on the results of this study, the use
      of self-etch adhesive resin (FL-Bond II) on the set glass-ionomer yielded the
      highest bond strength in the glass-ionomer/giomer sandwich technique.

PMID- 23559945
TI  - Effect of calcium hydroxide premedication on the marginal adaptation of calcium
      enriched mixture cement apical plug.
AB  - BACKGROUND: This study was to evaluate the effects of calcium hydroxide
      premedication on the marginal adaptation of the calcium-enriched mixture (CEM)
      cement as an apical plug. MATERIALS AND METHODS: In this in vitro study, forty
      single rooted teeth were prepared and apical portion of the roots were immersed
      in sulfuric acid to produce open apices. The teeth were divided into 2
      experimental groups. In medicated group, calcium hydroxide was placed in all
      canals for 1 week and in non-medicated group no dressing was used. Then, a 4-mm
      apical plug of CEM cement was placed in canals; each root was prepared for
      observation using scanning electron microscope and the maximum distance between
      CEM cement and surrounding dentin was measured. The data were analyzed by t-test,
      and significance level was set at alpha = 0.05. RESULTS: The mean width of gap in
      medicated and non-medicated groups was 158/1 MUm and 147/1 MUm, respectively.
      There was no significant difference between the two groups (P > 0.05).
      CONCLUSION: Calcium hydroxide premedication had no adverse effect on the marginal
      adaptation of CEM cement apical plug.

PMID- 23559946
TI  - Prevalence of early childhood caries among 3-5 year old pre-schoolers in schools
      of Marathahalli, Bangalore.
AB  - BACKGROUND: Dental caries among preschool children is still a major public health
      problem in many developing countries including India. Hence the aim of the
      present study was to find out the prevalence of Early Childhood Caries among 3-5
      year old pre-schoolers in schools of Marathahalli, Bangalore. MATERIALS AND
      METHODS: A cross sectional study was conducted on 717 pre-schoolers in 6 schools
      of Marathahalli. Clinical examination was performed and deft index was recorded
      using Gruebell's criteria. Early Childhood Caries was diagnosed using Early
      Childhood Caries Diagnostic Criteria, consistent with the NIDCR workshop
      statement. Data was analysed using SPSS 15.0 and descriptive statistics was
      applied. Chi-square test was used to find out the significant differences. The
      level of significance was taken at P value < 0.05. RESULTS: Prevalence of early
      childhood caries was 40% with a mean deft of 1.89 (+3.3) and Significant Caries
      Index score was 5.51. 44.8% of 3 year old had Early Childhood Caries, 35% of 4
      year old children and 41% of 5 year old had Early Childhood Caries. Almost, all
      of deft was due to untreated caries. CONCLUSION: The results of the present study
      calls for a need to focus on pre-schoolers' oral health and parental education
      for prevention and early detection of Early Childhood Caries. A high Significant
      Caries Index in this study population indicates a more targeted approach for high
      risk pre-schoolers.

PMID- 23559947
TI  - The parents' knowledge and behavior towards the effects of using iron supplements
      on tooth staining and dental caries in Mashhad, Iran.
AB  - BACKGROUND: Iron deficiency is estimated to be the most common nutritional
      deficiency in both developed and underdeveloped nations. Iron supplements at
      early age may prevent iron deficiency. The aim of this study was to assess the
      knowledge and management of parents about using iron supplements related to
      dental caries and staining among Iranian children (6 months to 2 year-old) and to
      identify some factors underlying these attitudes. MATERIALS AND METHODS: This
      randomized cross sectional study was carried out on the parents of 220 children
      (6 months to 2-year-old) evaluated in health services centers in Mashhad in 2008.
      Parents filled questionnaires assessing their opinions on the risk of using iron
      supplement on tooth staining and dental caries. The results were statistically
      analyzed by descriptive-analytical, Mann Whitney and Kruscal Wallis tests.
      RESULTS: According to this study the relation between iron supplement application
      with tooth staining and its effect on dental caries, it must be noted that most
      parents (82.7%) had a moderate range of knowledge. Major of the parents (72.7%)
      had a moderate level of behavior. There was a significant difference between the
      knowledge level of fathers with their level of education (P = 0.01). CONCLUSION:
      The finding of this study indicates that parental knowledge about consumption of
      iron supplements by their children (6 months to 2-year-old) has been moderate.
      But their behavior was poor and needs more attention.

PMID- 23559948
TI  - Factors affecting the willingness to pay for implants: A study of patients in
      Riyadh, Saudi Arabia.
AB  - BACKGROUND: One of the factors that dissuade patients needing tooth replacement
      from choosing dental implants is the prohibitive cost. Willingness to pay (WTP)
      is a useful tool to determine the ideal cost of an expensive procedure. AIM: The
      aim of this study was to study the factors that influence the willingness to pay
      (WTP) among patients attending a private clinic and compare them to those
      attending a government setup. MATERIALS AND METHODS: A total of 100 patients (38
      male, 62 female) who had one or more missing teeth were presented with different
      cost-benefit scenarios and then asked if they were willing to pay the median cost
      of a single implant in Riyadh city. The mean WTP price was compared using the one
      way-ANOVA, factors which could possibly influence patients' WTP were grouped
      together in a Binomial logistic regression model. RESULTS: Of the 100 individuals
      surveyed 67% said they would be willing to pay the median price for the placement
      of an implant. A comparison of socio-demographic factors showed that significant
      differences were found between gender, income groups and setting of the clinic in
      the mean WTP price of the patients (P < 0.05). We also found that there was a
      significant difference in the mean WTP price between groups with regard to the
      area of the missing tooth, the patients' perception of their oral health and the
      their desire to want an implant (P < 0.05). CONCLUSION: The majority of the
      patients surveyed were willing to pay the median price for an implant.
      Willingness to pay (WTP) is a multifactorial variable which is significantly
      influenced by the income of the patient, the setting of the clinic and the
      gender; the most significant factor being the acceptability of the implant to the
      patient.

PMID- 23559949
TI  - Odontogenic tumors in Iran, Isfahan: A study of 260 cases.
AB  - BACKGROUND: The aim of this study was to record the relative frequency of
      odontogenic tumors (OTs), evaluate and analyze the epidemiological features of
      the lesions in patients referring to dental faculty of Isfahan and compare these
      data with previous studies. MATERIALS AND METHODS: In this study, we reviewed the
      records of 6,860 lesions from 1988 to 2010 archived in the oral pathology
      department of dental faculty of Isfahan retrospectively and using criteria for
      histological typification published by the WHO in 2005. Age, sex, site and extent
      of tumors were analyzed. RESULTS: Among recorded lesions 260 were OTs (3.79%). Of
      these, 259 were benign and just 1 was malignant. The most common lesions were
      ameloblastomas (n = 95) followed by odontomas (n = 86), odontogenic myxomas (n =
      24) and others. There were a few more female patients (n = 133, 51.15%) than male
      and the mean age of patients was 27.8 years (range 1.5-80 years). The posterior
      of mandible was the most common site (n = 86, 33%). CONCLUSION: According to
      accumulated data, odontogenic tumors are uncommon lesions and malignant tumors
      are very rare.

PMID- 23559950
TI  - Association between early childhood caries, streptococcus mutans level and
      genetic sensitivity levels to the bitter taste of, 6-N propylthiouracil among the
      children below 71 months of age.
AB  - BACKGROUND: Oral health is an integral component of pre-school health and well
      being. Unfortunately, many children are afflicted with dental caries at an early
      age, even those as young as 12 months of age. The purpose of this study is to
      determine the association between Early Childhood Caries (ECC), Streptococcus
      mutans and genetic sensitivity levels to the bitter taste of, PROP among the
      children below 71 months of age. MATERIALS AND METHODS: Total of 119 children
      belonging to the age group of 36 to 71 months of both sexes, were recruited from
      A. J. Institute of Dental Sciences, Mangalore (Karnataka). PROP sensitivity test
      was carried out to determine the inherent genetic ability to taste a bitter or
      sweet substance. One who tasted bitter as taster and one who was not able to
      differentiate/tasted like paper as non-tasters. Facial expression was observed
      during the tasting to support the verbal response. Estimation of S. mutans level
      and caries experience was recorded. The results were statistically analyzed using
      Mann'Whiteney-U Test and Kruskal value test. RESULTS: In the total of 119
      children, the mean DMFS was definitely higher in non-taster children compared to
      tasters and also had a high S. mutans level. Tasters had low ECC experience, low
      S. mutans level. The tasters had a mean DMFS value of 9.5120 (S.D. 7.0543) and
      non-tasters had a value of 7.7250 (S.D. 8.33147), which was statistically
      significant. CONCLUSION: Children who had higher level S. mutans had ECC and were
      non tasters. The PROP sensitivity test (filter paper test) proved to be a useful
      diagnostic tool in determining the genetic sensitivity levels of bitter taste.
      Age and low socio-economic status of pre-school children suggest a complex
      multifactorial relationship between S. mutans colonization, ECC and taste
      perception.

PMID- 23559951
TI  - Influence of polymerization time and depth of cure of resin composites determined
      by Vickers hardness.
AB  - BACKGROUND: Adequate polymerization of resin composites could be considered as a
      crucial factor in obtaining good clinical performance, particularly in stress
      bearing areas. An insufficient curing degree affects the resin composite's
      chemical properties The current in vitro study evaluated the influence of
      polymerization time and depth of cure of six commercial resin composites by
      Vickers microhardness (VK). MATERIALS AND METHODS: SIX RESIN COMPOSITES WERE
      SELECTED: Three microhybrid (Esthet.X HD, Amaris, Filtek Silorane), two
      nanohybrid (Grandio, Ceram.X mono), and one nanofilled (Filtek Supreme XT). The
      VK of the surface was determined by a microhardness tester using a Vickers
      diamond indenter and a 200 g load applied for 15 s. The bottom to top mean VK
      ratio was calculated using the formula: Hardness ratio = VK of bottom surface/VK
      of top surface. Vickers hardness values of test materials during exposure time of
      20 and 40 s and depths of cure of 2 and 3 mm were determined and compared. Data
      were analyzed using analysis of variance (ANOVA) test. RESULTS: For all the
      tested materials and with all the exposure time periods, hardness ratio was
      higher than the minimum value indicated in literature (0.8). Exposure time and
      depth of cure did not affect hardness ratio values for Filtek Silorane, Grandio,
      and Filtek Supreme XT. CONCLUSION: Among the materials tested, the nanofilled and
      the nanohybrid resin composites were rather insensible to thickness variations.
      Miicrohybrid composites, instead, had features different from one another.

PMID- 23559952
TI  - Evaluation of stress distribution of implant-retained mandibular overdenture with
      different vertical restorative spaces: A finite element analysis.
AB  - BACKGROUND: Available restorative space and bar height is an important factor in
      stress distribution of implant-supported overdentures. The purpose of this study
      was to evaluate the effect of different vertical restorative spaces and different
      bar heights on the stress distribution around implants by 3D finite element
      analysis. MATERIALS AND METHODS: 3D finite element models were developed from
      mandibular overdentures with two implants in the interforaminal region. In these
      models, four different bar heights from gingival crest (0.5, 1, 1.5, 2 mm) with
      15 mm occlusal plane height and three different occlusal plane heights from
      gingival crest (9, 12, 15 mm) with 2 mm bar height were analyzed. A vertical
      unilateral and a bilateral load of 150 N were applied to the central occlusal
      fossa of the first molar and the stress of bone around implant was analyzed by
      finite element analysis. RESULTS: By increasing vertical restorative space, the
      maximum stress values around implants were found to be decreased in unilateral
      loading models but slightly increased in bilateral loading cases. By increasing
      bar height from gingival crest, the maximum stress values around implants were
      found to be increased in unilateral loading models but slightly decreased in
      bilateral loading cases. In unilateral loading models, maximum stress was found
      in a model with 9 mm occlusal plane height and 1.5 mm bar height (6.254 MPa), but
      in bilateral loading cases, maximum stress was found in a model with 15 mm
      occlusal plane height and 0.5 mm bar height (3.482 MPa). CONCLUSION: The
      reduction of bar height and increase in the thickness of acrylic resin base in
      implant-supported overdentures are biomechanically favorable and may result in
      less stress in periimplant bone.

PMID- 23559953
TI  - Evaluation of orofacial lesions relating child abuse, Esfahan, Iran: A
      quantitative approach.
AB  - BACKGROUND: Family violence, including child abuse, neglect, and domestic
      violence, is a public health problem. The aim of this study was to provide data
      on prevalence and factors of Orofacial lesions relating child abuse in Iran to
      lend evidence to support preventing child abuse. MATERIALS AND METHODS: The
      overall approach was a case-note review of children having child abuse note,
      recording by personnel of social services. Research ethical approval was sought
      from the Central social service organization. This study was conducted in
      Isfahan, Iran (2011). RESULT: The mean age of children, when abuse had been
      occurred was 8 years (SD = 1.68), and there were approximately an equal number of
      boys and girls. Children had a high physical experience (66.1%).Of these
      children, at least 60% sustained trauma to the face and mouth. Emotional abuse
      was 77.1%, neglect was 64.1%, and lower experience of sexual abuse which was
      4.1%. There was a strong relationship between gender and abuser which shows girls
      have been affected by stepfathers (P = 0.001). CONCLUSION: Preliminary data
      suggest that there are strong evidence regarding the incidence of child abuse
      relating orofacial lesions which dentists should be aware of them. Future trials
      may draw on these useful baseline data to help their study design.

PMID- 23559954
TI  - Receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in
      gingival crevicular fluid.
AB  - BACKGROUND: OSTEOCLASTOGENESIS IS COORDINATED BY THE INTERACTION OF THREE MEMBERS
      OF THE TUMOR NECROSIS FACTOR (TNF) SUPERFAMILY: Osteoprotegerin (OPG)/receptor
      activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear
      factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG
      levels, and their relative ratio in gingival crevicular fluid (GCF) of patients
      with chronic and aggressive periodontitis, as well as healthy controls. MATERIALS
      AND METHODS: In this analytical study, GCF was obtained from healthy (n = 10),
      mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18),
      severe chronic periodontitis (n = 20), and generalized aggressive periodontitis
      (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked
      immunosorbent assay. Statistical tests used were Kruskal-Wallis test, Mann
      Whitney U rank sum test, and Spearman's rank correlation analysis. The level of
      statistical significance was set at P < 0.05. RESULTS: Mean RANKL concentration
      showed no statistically significant differences between groups (P = 0.58). There
      were also no significant differences between mean OPG concentration in the five
      groups (P = 0.0.56). Moreover, relative RANKL/OPG ratio did not reveal a
      significant difference between the three study group subjects: healthy, chronic
      periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41).
      There was statistically significant correlation between the concentration of
      sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis
      patients (R = 0.48, P = 0.04). There was also negative correlation between OPG
      concentration and CAL in moderate chronic periodontitis patients, although not
      significant (R = -0.13). CONCLUSION: RANKL was prominent in periodontitis sites,
      especially in moderate periodontitis patients, whereas OPG was not detectable in
      some diseased sites with bleeding on probing, supporting the role of these two
      molecules in the bone loss developed in this disease.

PMID- 23559955
TI  - Clinical and biometrical evaluation of socket preservation using demineralized
      freeze-dried bone allograft with and without the palatal connective tissue as a
      biologic membrane.
AB  - BACKGROUND: Alveolar ridge preservation following tooth extraction has the
      ability to maintain the ridge dimensions and allow the implant placement in an
      ideal position fulfilling both functional and aesthetic results. The aim of this
      study was to evaluate the efficacy of the palatal connective tissue as a
      biological membrane for socket preservation with demineralized freeze-dried bone
      allograft (DFDBA). MATERIALS AND METHODS: Twelve extraction sites were treated
      with DFDBA with (case group) and without (control group) using autogenous palatal
      connective tissue membrane before placement of implants. Alveolar width and
      height, amount of keratinized tissue, and gingival level were measured at pre
      determined points using a surgical stent at two times, the time of socket
      preservation surgery. RESULTS: In both groups a decrease in all socket dimensions
      was found. The average decrease in socket width, height, keratinized tissue, and
      gingival level in case group was 1.16, 0.72, 3.58, and 1.27 mm, and in control
      group was 2.08, 0.86, 4.52, and 1.58 mm respectively. Statistical analysis showed
      that decrease in socket width (P = 0.012), keratinized tissue (P <= 0.001), and
      gingival level (P = 0.031) in case group was significantly lower than that of the
      control group. Results showed no meaningful difference in socket height changes
      when compared with case and control groups (P = 0.148). CONCLUSION: Under the
      limits of this study, connective tissue membrane could preserve socket width,
      amount of keratinized tissue, and the gingival level more effectively than DFDBA
      alone.

PMID- 23559957
TI  - Is periodontal disease related to preeclampsia?
AB  - BACKGROUND: Several studies have hypothesized that periodontal diseases may
      increase the risk of preeclampsia. The purpose of this study was to compare
      periodontal parameters in preeclamptic and normotensive pregnant women 48 hours
      after delivery. MATERIALS AND METHODS: A case-control study was carried out on 26
      pure preeclamptic women and 25 women with normal pregnancy. The participants did
      not have any systemic disease that may affect both preeclampsia and periodontal
      conditions. Clinical parameters measured in case and control groups include
      attachment loss, gingival bleeding index, and plaque index. These indices were
      measured in all teeth except the third molars. The data from each subject were
      reported in mean and finally the average amount of each group was compared to
      others and analyzed using SPSS software, t-test, and Mann-Whitney test. RESULTS:
      Mean of gestational age at delivery in preeclamptic and normotensive groups was
      respectively 33.2 +/- 3.89 weeks and 36.5 +/- 3.08 weeks. A significant
      difference was observed in preeclamptic women compared to controls (P = 0.01).
      There were no statistical differences between groups with regard to mean clinical
      attachment loss (P = 0.16), mean gingival bleeding (P = 0.89), and mean plaque (P
      = 0.95) indices. CONCLUSION: The present study showed that maternal periodontal
      diseases during pregnancy are not associated with preeclampsia.

PMID- 23559956
TI  - Effect of framework design on fracture resistance of zirconium oxide posterior
      fixed partial dentures.
AB  - INTRODUCTION: The effect of framework design modifications in all-ceramic systems
      is not fully understood. The aim of this investigation was to evaluate the effect
      of different framework designs on fracture resistance of zirconium oxide
      posterior fixed partial dentures (FPD). MATERIALS AND METHODS: Thirty two
      posterior zirconia FPD cores were manufactured to replace a second premolar. The
      specimens were divided into four groups; I: 3 * 3 connector and standard design,
      II: 3 * 3 connector and modified design, III: 4 * 4 connector dimension, and
      standard design and IV: 4 * 4 connector dimension and modified design. After
      storing for one week in artificial saliva and thermocycling (2000 cycles, 5-55
      degrees C), the specimens were loaded in a universal testing machine at a
      constant cross-head speed of 0.5 mm/min until failure occurred. The Weibull,
      Kruskal-Wallis, and Mann-Whitney tests were used for statistical analysis (alpha
      = 0.05). RESULTS: The mean fracture resistance of groups with 4 * 4 mm connector
      was significantly higher than groups with 3 * 3 mm connector (P < 0.001).
      Although, the fracture resistance of the modified frameworks was increased in the
      present study (1.1 times), they were not significantly different from anatomic
      specimens (P = 0.327). CONCLUSIONS: The fracture resistance of the zirconia
      posterior-fixed partial dentures was significantly affected by the connector
      size; it was not affected by the framework modification.

PMID- 23559958
TI  - Gingival crevicularfluid osteoprotegerin levels in Indian population.
AB  - BACKGROUND: Initial research indicated that higher concentration of
      osteoprotegerin (OPG) is associated with healthy periodontium (protective) and
      its concentration decreases as the periodontal disease progresses. However, till
      date, there are no studies to investigate the levels of OPG in gingival
      crevicular fluid (GCF) after the treatment of periodontitis. Hence, the present
      study was carried out to assess its concentration in GCF to find out their
      association if any, and to explore its possible use as a 'novel bone marker' of
      the host modulation of periodontal disease. MATERIALS AND METHODS: Sixty-four
      subjects were divided into 4 groups (16 each), based on clinical attachment loss
      (CAL) and radiological parameters (bone loss); healthy (group I), gingivitis
      (group II), slight periodontitis (group III), and moderate-to-severe
      periodontitis (group IV). Moderate-to-severe periodontitis subjects, after
      nonsurgical periodontal treatment, (SRP) constituted group V. GCF samples were
      collected to estimate the levels of OPG using enzyme-linked immunosorbent assay
      (ELISA). The Kruskal-Wallis, Man-Whitney U test, and Wilcoxon signed-rank tests
      were carried out to compare OPG levels among groups. The Spearman rank
      correlation test was used to correlate OPG levels between the study groups and
      the clinical parameters; P < 0.05 was considered significant. RESULTS: The
      highest mean OPG concentration in GCF was obtained for group I (162.47 +/- 51.171
      pg/ MUL) and the least for group IV (10.92 +/- 1.913 pg/MUL), suggesting a
      negative correlation between OPG concentration and CAL. OPG concentrations in GCF
      after the treatment of group IV increased from 10.92 +/- 1.913 pg/MUL to 15.63 +/
      4.679 pg/MUL. CONCLUSION: OPG concentration in GCF was inversely proportional to
      CAL and not an active progression factor for periodontal disease. Further, after
      the treatment of moderate-to-severe periodontitis subjects (group IV), OPG
      concentrations increased. Hence, it can be concluded that OPG could be considered
      as a 'novel bone marker' the host modulation of periodontal disease.

PMID- 23559959
TI  - Effects of flapless bur decortications on movement velocity of dogs' teeth.
AB  - BACKGROUND: Different surgical procedures that reduce orthodontic treatment time
      have been recommended. The aim of this study was to evaluate the effectiveness of
      a new less invasive surgical technique (called flapless bur decortications) for
      accelerating orthodontic tooth movement. MATERIALS AND METHODS: This study was
      designed as a split-mouth study. The left and right maxillary first premolars of
      five dogs were extracted. An A-NiTi closed coil spring and an absolute anchorage
      was used for premolar protraction in both sides. In each dog, decortications were
      performed for one side and the other side was used as the control group. The
      distance between canine and second premolar was measured and the sites of
      decortication were evaluated histologically. The data was analyzed by paired
      samples t-test and multivariate analysis of two-way repeated measures ANOVA.
      RESULTS: The study teeth moved more than their controls in the first month and
      less than their controls in the third month (P < 0.05). The total difference
      between study and control movements was not significant (P < 0.05). CONCLUSION:
      (1) Corticotomy facilitated orthodontic tooth movement is achievable with
      flapless bur decortication technique. (2) Velocity of tooth movement decreases in
      later stages of treatment due to maturation of newly formed bone at decortication
      sites.

PMID- 23559960
TI  - Effect of enamel matrix derivative on bone formation around intraosseous titanium
      implant: An experimental study in canine model.
AB  - BACKGROUND: The purpose of this study was to perform a histological,
      histomorphometrical, and immunohistochemical evaluation of the effect of Enamel
      matrix derivative (EMD) on bone formation around titanium dental implant.
      MATERIALS AND METHODS: In this animal study, 12 implants (10 * 3.8 mm) were
      inserted in the tibia bone of three dogs of Iranian breed. Two implants were
      placed in each tibia with EMD only on the left side. The dogs were sacrificed 2,
      4, and 6 weeks after implantation. Following decalcification of the implants'
      surrounding tissue and preparation of 4 MUm thick sections, they were stained
      with hematoxylin and eosin (H and E) and immunohistochemical (IHC) stain for
      osteopontin (OPN) marker. Histomorphometric evaluation was performed via
      measurement of the percentage of the woven, lamellar, and total generated bone.
      Light microscopy osteoblastic intensity of OPN in osteoblasts and bone matrix was
      also evaluated Data were analyzed by Wilcoxon signed Ranks, and Mc Nemar tests.
      RESULTS: In both control and EMD-applied groups, bone formation was recognized
      around the implants at the 4(th) week postimplantation. The percentage of total
      generated bone in the test group was higher than the control group, although
      being not statistically significant (P value = 0.917). Osteoclasts exhibited
      significantly higher proliferation activity compared the control group when
      stimulated by EMD (P value = 0.027). On average, the staining intensity in
      osteoblasts and extracellular matrix of bone, in EMD-applied subjects was higher
      than those of the controls (P value = 0.167 and P value = 0.414, respectively).
      CONCLUSION: EMD enhanced bone formation around dental implants, but this increase
      was not significant.

PMID- 23559961
TI  - Paramolar - A supernumerary molar: A case report and an overview.
AB  - Paramolar is a supernumerary molar usually small and rudimentary, most commonly
      situated buccally or palatally to one of the maxillary molars. Paramolar is a
      developmental anomaly and has been argued to arise from a combination of genetic
      and environmental factors. Reports of this entity are rarely found in the dental
      literature. This article presents a case report of an unusual occurrence of a
      paramolar in the maxilla in otherwise a healthy individual. In addition,
      literature review, prevalence, classification, etiology, complications,
      diagnosis, and therapeutic strategies that may be adopted when supernumeraries
      occurs have been discussed.

PMID- 23559962
TI  - Perforation of the hard palate due to tuberculosis.
AB  - Tuberculosis (TB) of the hard palate is rare and usually secondary to pulmonary
      TB. We present a case of a 7-year-old boy who presented with difficulty in
      swallowing solid foods, low-grade fever and loss of weight. Oral cavity
      examination showed perforation of the hard palate with an irregular, undermined
      margin and a necrotic base. Chest X-ray showed homogeneous opacity in the right
      upper zone. Fine-needle aspiration of the cervical lymph nodes showed granular
      caseous necrosis and granuloma composed of epitheliod cells and histiocytes. In
      view of the clinical presentation and evidence of pulmonary and lymph node TB,
      the palatal perforation was most likely due to TB. Patient was started on
      antituberculous therapy and is on regular follow-up.

PMID- 23559963
TI  - Surgical orodental implications in ankylosing spondylitis.
AB  - Temporomandibular joint and the pelvic complex are bidirectionally related.
      Ankylosing spondylitis (AS) is a seronegative arthropathy with the key feature of
      bony fusion of lumbar vertebrae. A 39 year old known case of AS was presented to
      private office for left lower impacted third molar surgical removal. Previously,
      he was rejected to receive oral care for pulpectomy and extraction due to limited
      mouth opening. Prior to the surgery, lateral neck radiography was obtained to
      exclude any subluxation of fracture of cervical vertebrae. Neck was supported to
      insure neck stability during surgical forces. In addition, considering
      consumption of immunosuppressive medications including corticosteroids, procedure
      was performed with a great care, with attention to higher possibility of
      infection and fracture. Access to the surgical site was not desirable, though
      surgery accomplished without any significant event and the patient discharged
      with routine analgesic and antibiotics recommendation. Sometimes, impaired access
      to the oral cavity in patients with AS leads to receive suboptimal or minimal
      orodental care. Long list of dental implications in these patients may be
      simplified by considering of careful neck and jaw support, applying at least
      possible forces and great attention to the infection control rules. It is wised
      to be performed under patient and skilled hands.

PMID- 23559964
TI  - Pediatric oral pulse granuloma: A rare entity.
AB  - A pulse granuloma is nothing but a reaction of the foreign body to any vegetable
      which is characterized by a collection of the hyaline; a hyaline is a transparent
      substance that is formed from the pathological degeneration of the tissue. These
      granulomatous rings may be oral or extra-oral. It is important to recognize such
      a type of granuloma because it may resemble serious pathological processes or may
      clinically stimulate neoplasia. It might also be confused morphologically with
      hyaline vasculopathy. The following manuscript presents a rare case of oral pulse
      granuloma. As going by the literature-search, the following being the only case
      to have been occurred in a pediatric patient. The authors therefore aim to bring
      awareness amongst the pediatric dentists about its etiology, occurrence, clinical
      features and thereby management of the same.

PMID- 23559965
TI  - Gingival plasma cell granuloma.
AB  - Plasma cell granuloma, also known as inflammatory pseudotumor is a tumor-like
      lesion that manifests primarily in the lungs. But it may occur in various other
      anatomic locations like orbit, head and neck, liver and rarely in the oral
      cavity. We here report an exceedingly rare case of gingival plasma cell granuloma
      in a 58 year old woman who presented with upper gingival polypoidal growth. The
      histopathological examination revealed a mass composed of proliferation of benign
      spindle mesenchymal cells in a loose myxoid and fibrocollagenous stroma along
      with dense infiltrate of chronic inflammatory cells predominantly containing
      plasma cells. Immunohistochemistry for kappa and lambda light chains showed a
      polyclonal staining pattern confirming a diagnosis of plasma cell granuloma.

PMID- 23559966
TI  - Management of polyostotic eosinophilic granuloma.
AB  - Eosinophilic granuloma is a rare disease which is difficult to diagnose
      clinically and radiographically. Localized Langerhans' cell histiocytosis,
      previously known as eosinophilic granuloma, mainly affects the skull, mandible,
      vertebrae, pelvis and ribs in children and the long bones of adults. We present a
      case report of a female who developed pain and swelling over the left mandibular
      region, and was later diagnosed as eosinophilic granuloma, which after
      administration of intralesional corticosteroid with surgical enucleation showed
      positive response. This disease is of importance to dental professionals because
      early clinical signs can occur in the jaw and can cause extensive destruction of
      the periodontal tissues and bone. The purpose of this case report is to describe
      a case of eosinophilic granuloma with emphasis on conservative approach for the
      treatment and the radiographic changes observed during and after the treatment.

PMID- 23559967
TI  - "3D bite": A new appliance device for registration of construction bite.

PMID- 23559968
TI  - Evaluation the compressive and diametric tensile strength of nano and hybrid
      composites.

PMID- 23559969
TI  - Iranian dental students' knowledge, attitudes, and health behavior toward HIV
      patients.

PMID- 23559970
TI  - Right ventricular failure in congenital heart disease.
AB  - Despite developments in surgical techniques and other interventions, right
      ventricular (RV) failure remains an important clinical problem in several
      congenital heart diseases (CHD). RV function is one of the most important
      predictors of mortality and morbidity in patients with CHD. RV failure is a
      progressive disorder that begins with myocardial injury or stress, neurohormonal
      activation, cytokine activation, altered gene expression, and ventricular
      remodeling. Pressure-overload RV failure caused by RV outflow tract obstruction
      after total correction of tetralogy of Fallot, pulmonary stenosis, atrial switch
      operation for transposition of the great arteries, congenitally corrected
      transposition of the great arteries, and systemic RV failure after the Fontan
      operation. Volume-overload RV failure may be caused by atrial septal defect,
      pulmonary regurgitation, or tricuspid regurgitation. Although the measurement of
      RV function is difficult because of many reasons, the right ventricle can be
      evaluated using both imaging and functional modalities. In clinical practice,
      echocardiography is the primary mode for the evaluation of RV structure and
      function. Cardiac magnetic resonance imaging is increasingly used for evaluating
      RV structure and function. A comprehensive evaluation of RV function may lead to
      early and optimal management of RV failure in patients with CHD.

PMID- 23559971
TI  - Oxidative stress and the antioxidant enzyme system in the developing brain.
AB  - Preterm infants are vulnerable to the oxidative stress due to the production of
      large amounts of free radicals, antioxidant system insufficiency, and immature
      oligodendroglial cells. Reactive oxygen species (ROS) play a pivotal role in the
      development of periventricular leukomalacia. The three most common ROS are
      superoxide (O2(*-)), hydroxyl radical (OH(*)), and hydrogen peroxide (H2O2).
      Under normal physiological conditions, a balance is maintained between the
      production of ROS and the capacity of the antioxidant enzyme system. However, if
      this balance breaks down, ROS can exert toxic effects. Superoxide dismutase,
      glutathione peroxidase, and catalase are considered the classical antioxidant
      enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx),
      is also an important scavenger of free radicals. Prdx1 expression is induced at
      birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is
      consistent with the classical antioxidant enzymes. Several antioxidant substances
      have been studied as potential therapeutic agents; however, further preclinical
      and clinical studies are required before allowing clinical application.

PMID- 23559972
TI  - Analysis of the association between necrotizing enterocolitis and transfusion of
      red blood cell in very low birth weight preterm infants.
AB  - PURPOSE: To investigate the association between necrotizing enterocolitis (NEC)
      and red blood cell transfusions in very low birth weight (VLBW) preterm infants.
      METHODS: We studied were 180 VLBW preterm infants who were admitted to the
      neonatal intensive care unit of CHA Gangnam Hospital from January of 2006 to
      December of 2009. The subjects were divided into 2 groups: an NEC group (greater
      than stage II on the modified Bell's criteria) and a control group (less than
      stage II on the modified Bell's critieria). We defined red blood cell transfusion
      before NEC diagnosis as the frequency of transfusion until NEC diagnosis (mean
      day at NEC diagnosis, day 18) in the NEC group and the frequency of transfusion
      until 18 days after birth in the control group. RESULTS: Of the 180 subjects, 18
      (10%) belonged to the NEC group, and 14 (78%) of these 18 patients had a history
      of transfusion before NEC diagnosis. The NEC group received 3.1+/-2.9
      transfusions, and the control group received 1.0+/-1.1 transfusions before the
      NEC diagnosis (P=0.005). In a multivariate logistic regression corrected for
      gestational age, Apgar score at 1 minute, the presence of respiratory distress
      syndrome, patent ductus arteriosus, premature rupture of membrane, disseminated
      intravascular coagulopathy and death were confounding factors. The risk of NEC
      increased 1.63 times (95% confidence interval, 1.145 to 2.305; P=0.007) with
      transfusion before the NEC diagnosis. CONCLUSION: The risk for NEC increased
      significantly with increased transfusion frequency before the NEC diagnosis.

PMID- 23559973
TI  - An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression
      in monocrotaline-induced pulmonary hypertensive rats model.
AB  - PURPOSE: Tumor necrosis factor (TNF)-alpha is thought to contribute to pulmonary
      hypertension. We aimed to investigate the effect of infliximab (TNF-alpha
      antagonist) treatment on pathologic findings and gene expression in a
      monocrotaline-induced pulmonary hypertension rat model. METHODS: Six-week-old
      male Sprague-Dawley rats were allocated to 3 groups: control (C), single
      subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single
      subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline +
      infliximab (M+I), single subcutaneous injection of monocrotaline plus single
      subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1,
      5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels
      of TNF-alpha, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial
      nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)2, and tissue
      inhibitor of matrix metalloproteinase (TIMP). RESULTS: The increase in medial
      wall thickness of the pulmonary arteriole in the M+I group was significantly
      lower than that in the M group on day 7 after infliximab treatment (P<0.05). The
      number of intra-acinar muscular arteries in the M+I group was lower than that in
      the M group on days 14 and 28 (P<0.05). Expression levels of TNF-alpha, ET-1,
      ERA, and MMP2 were significantly lower in the M+I group than in the M group on
      day 5, whereas eNOS and TIMP expressions were late in the M group (day 28).
      CONCLUSION: Infliximab administration induced early changes in pathological
      findings and expression levels of TNF-alpha, and MMP2 in a monocrotaline-induced
      pulmonary hypertension rat model.

PMID- 23559974
TI  - Implantable cardioverter defibrillator therapy in pediatric and congenital heart
      disease patients: a single tertiary center experience in Korea.
AB  - PURPOSE: The use of implantable cardioverter defibrillators (ICDs) to prevent
      sudden cardiac death is increasing in children and adolescents. This study
      investigated the use of ICDs in children with congenital heart disease. METHODS:
      This retrospective study was conducted on the clinical characteristics and
      effectiveness of ICD implantation at the department of pediatrics of a single
      tertiary center between 2007 and 2011. RESULTS: Fifteen patients underwent ICD
      implantation. Their mean age at the time of implantation was 14.5+/-5.4 years
      (range, 2 to 22 years). The follow-up duration was 28.9+/-20.4 months. The cause
      of ICD implantation was cardiac arrest in 7, sustained ventricular tachycardia in
      6, and syncope in 2 patients. The underlying disorders were as follows: ionic
      channelopathy in 6 patients (long QT type 3 in 4, catecholaminergic polymorphic
      ventricular tachycardia [CPVT] in 1, and J wave syndrome in 1), cardiomyopathy in
      5 patients, and postoperative congenital heart disease in 4 patients. ICD coils
      were implanted in the pericardial space in 2 children (ages 2 and 6 years). Five
      patients received appropriate ICD shock therapy, and 2 patients received
      inappropriate shocks due to supraventricular tachycardia. During follow-up, 2
      patients required lead dysfunction-related revision. One patient with CPVT
      suffered from an ICD storm that was resolved using sympathetic denervation
      surgery. CONCLUSION: The overall ICD outcome was acceptable in most pediatric
      patients. Early diagnosis and timely ICD implantation are recommended for
      preventing sudden death in high-risk children and patients with congenital heart
      disease.

PMID- 23559975
TI  - Vascular endothelial dysfunction after anthracyclines treatment in children with
      acute lymphoblastic leukemia.
AB  - PURPOSE: Anthracyclines have been utilized in the treatment of children with
      acute lymphoblastic leukemia (ALL). Recent studies have shown that anthracyclines
      may induce toxicity in the vascular endothelium. This study was performed using
      brachial artery reactivity (BAR) to evaluate vascular endothelial function in ALL
      patients who were treated with anthracycline chemotherapy. METHODS: We included
      21 children with ALL who received anthracycline chemotherapy and 20 healthy
      children. The cumulative dose of anthracyclines in the ALL patients was 142.5+/
      18.2/m(2). The last anthracycline dose was administered to the patients 2 to 85
      months prior to their examination using BAR. The diameter of the brachial artery
      was measured in both groups using echocardiography, and BAR was calculated as the
      percentage change in the arterial diameter after release of the cuff relative to
      the baseline vessel diameter. RESULTS: In the anthracycline-treated group, BAR
      was observed to be 3.4%+/-3.9%, which was significantly lower than that observed
      in the control group (12.1%+/-8.0%, P<0.05). The time elapsed after the last
      anthracycline treatment and the age at the time of treatment did not affect the
      change in BAR (P=0.06 and P=0.13, respectively). CONCLUSION: These results
      provided evidence that treatment of ALL patients with anthracycline results in
      endothelial dysfunction. A larger cohort study and a longer follow-up period will
      be required to clarify the relationship between endothelial dysfunction resulting
      from anthracycline treatment for childhood ALL and occurrence of cardiovascular
      diseases later in life.

PMID- 23559976
TI  - A girl with sternal malformation/vascular dysplasia association.
AB  - Sternal malformation/vascular dysplasia association is a rare congenital
      dysmorphology, which has not yet been reported in Korea. Its typical clinical
      features include a sternal cleft covered with atrophic skin, a median abdominal
      raphe extending from the sternal defect to the umbilicus, and cutaneous
      craniofacial hemangiomata. We report a case of a full-term newborn who presented
      with no anomalies at birth, except for a skin defect over the sternum and a
      supraumbilical raphe. Multiple hemangiomas appeared subsequently on her chin and
      upper chest wall, and respiratory distress due to subglottic hemangioma developed
      during the first 2 months of life. Her symptoms were controlled with oral
      prednisolone administration. No respiratory distress have recurred during the 3
      year follow-up period.

PMID- 23559977
TI  - X-linked recessive myotubular myopathy with MTM1 mutations.
AB  - X-linked recessive myotubular myopathy (XLMTM) is a severe congenital muscle
      disorder caused by mutations in the MTM1 gene and characterized by severe
      hypotonia and generalized muscle weakness in affected males. It is generally a
      fatal disorder during the neonatal period and early infancy. The diagnosis is
      based on typical histopathological findings on muscle biopsy, combined with
      suggestive clinical features. We experienced a case of a newborn who required
      intubation and ventilator care because of profound hypotonia and respiratory
      difficulty. The preliminary diagnosis at the time of request for retrieval was
      hypoxic ischemic encephalopathy, but the infant was clinically reevaluated for
      generalized weakness and muscle atrophy. Muscle biopsies showed variability in
      fiber size and centrally located nuclei in nearly all the fibers. We detected an
      MTM1 gene mutation of c.1261-1C>A in the intron 10 region, and diagnosed the
      neonate with myotubular myopathy. The same mutation was detected in his mother.

PMID- 23559980
TI  - Egypt and the neurosurgical transition in Africa.

PMID- 23559981
TI  - The study of flow diversion effects on aneurysm using multiple enterprise stents
      and two flow diverters.
AB  - BACKGROUND: Computer-based simulation is necessary to clarify the hemodynamics in
      brain aneurysm. Specifically for endovascular treatments, the effects of
      indwelling intravascular devices on blood stream need to be considered. The most
      recent technology used for cerebral aneurysm treatment is related to the use of
      flow diverters to reduce the amount of flow entering the aneurysm. To verify the
      differences of flow reduction, we analyzed multiple Enterprise stents and two
      kinds of flow diverters. MATERIALS AND METHODS: In this research, we virtually
      modeled three kinds of commercial intracranial stents (Enterprise, Silk, and
      Pipeline) and mounted to fit into the vessel wall, and deployed across the neck
      of an IC-ophthalmic artery aneurysm. Also, we compared the differences among
      multiple Enterprise stents and two flow diverters in a standalone mode. RESULTS:
      From the numerical results, the values of wall shear stress and pressure are
      reduced in proportion to the size of mesh, especially in the inflow area.
      However, the reduced velocity within the aneurysm sac by the multiple stents is
      not as significant as the flow diverters. CONCLUSIONS: This is the first study
      analyzing the flow alterations among multiple Enterprise stents and flow
      diverters. The placement of small meshed stents dramatically reduced the
      aneurysmal fluid movement. However, compared to the flow diverters, we did not
      observe the reduction of flow velocity within the aneurysm by the multiple
      stents.

PMID- 23559979
TI  - Gonad morphogenesis and distal tip cell migration in the Caenorhabditis elegans
      hermaphrodite.
AB  - Cell migration and morphogenesis are key events in tissue development and
      organogenesis. In Caenorhabditis elegans, the migratory path of the distal tip
      cells determines the morphology of the hermaphroditic gonad. The distal tip cells
      undergo a series of migratory phases interspersed with turns to form the gonad. A
      wide variety of genes have been identified as crucial to this process, from genes
      that encode components and modifiers of the extracellular matrix to signaling
      proteins and transcriptional regulators. The connections between extracellular
      and transmembrane protein functions and intracellular pathways are essential for
      distal tip cell migration, and the integration of this information governs gonad
      morphogenesis and determines gonad size and shape.

PMID- 23559982
TI  - Mechanical thrombectomy devices for endovascular management of acute ischemic
      stroke: Duke stroke center experience.
AB  - BACKGROUND: Mechanical thrombectomy devices are gaining popularity in large
      vessel occlusions where chemical thrombolysis is usually futile. MERCI, Multi
      MERCI, Penumbra and SWIFT trails have elevated the status of mechanical
      thrombectomy from being a complementary treatment modality to mainstream stroke
      intervention. The aim of this study was to compare our immediate recanalization
      rates with available mechanical devices. MATERIALS AND METHODS: A retrospective
      review from March 2009 to August 2012 was performed on patients who underwent
      mechanical thrombectomy for large vessel occlusion. Cases where IATPA and/or
      balloon angioplasty was performed without mechanical thrombectomy were excluded
      from the study. Recanalization rates were assessed immediately post-procedure by
      follow-up angiography. TICI scores were used to quantify the extent of
      recanalization and the residual clot burden. RESULTS: Twenty two procedures were
      performed on 20 patients using Merci (MER):5; Penumbra (PEN):11; Solitaire-FR
      (SOL):6. Two patients underwent intervention using both Merci and Penumbra
      devices. The M:F ratio was 1.2:1. The most common vascular territory involved was
      the right MCA (9/20) followed by left MCA (5/20), left ICA (2/20), basilar (3/20)
      and vertebral arteries (1/20). The average door to needle time was 210 minutes
      [MER: 184.4; PEN: 249.2; SOL: 162]. Additional procedures were performed in 63.4%
      (14/22) of the patients [MER: 80% (4/5); PEN: 72.7% (8/11) and SOL: 33.3% (2/6)].
      Vasospasm was observed in MER: 20% (1/5); PEN: 9.1% (1/11); SOL: 0% (0/6)].
      Complete recanalization was achieved in 59.1% (13/22) [MER: 40% (2/5); PEN: 45.5%
      (5/11); SOL: 100% (6/6)]. The rate of complete recanalization was statistically
      significant for the Solitaire group vs. the MERCI group (P=0.0062) as well as the
      Penumbra group (0.0025). The average pre-procedure TICI was 0.4 [MER: 0.6; PEN:
      0.3; SOL: 0.3], while the average post-procedure TICI was 2.5 [MER: 2.4; PEN:
      2.3; SOL: 3.0]. CONCLUSIONS: The study reveals a higher rate of angiographic
      recanalization using the Solitaire-FR device, requiring a lesser number of passes
      and other associated procedures as compared to MERCI and Penumbra. Thus,
      Stentrievers (Solitaire-FR) are advantageous in faster device delivery and quick
      flow restoration. However, future prospective randomized large trials are
      required to confirm these early results.

PMID- 23559983
TI  - Effects of a head-down tilt on cerebral blood flow in mice during bilateral
      common carotid artery occlusion.
AB  - OBJECTIVES: Data on the optimal head position for patients with acute ischemic
      stroke are unavailable. We evaluated the effects of mild head-down tilt (HDT) on
      cerebral blood flow (CBF) in mice during bilateral common carotid artery
      occlusion (BCCAO). MATERIALS AND METHODS: We used mice with BCCAO (35 minutes)
      and divided these into 2 groups ( n=16): BCCAO at 0 degrees -HDT and 5 degrees 
      HDT. CBF was measured for both hemispheres with a non-invasive laser Doppler
      blood perfusion imager. Changes in CBF during BCCAO were examined in both groups.
      RESULTS: A significantly greater increase in CBF in both hemispheres was observed
      in 5 degrees -HDT mice than in 0 degrees -HDT mice (126.1% (8.715)% vs. 102.1%
      (4.718)%; P=0.0294). CONCLUSION: HDT enhanced the increase in CBF in both
      hemispheres in the mouse BCCAO model. The potential mechanism underlying CBF
      increase enhanced by HDT during BCCAO warrants further investigation.

PMID- 23559984
TI  - AVM Compartments: Do they modulate trasnidal pressures? An electrical network
      analysis.
AB  - BACKGROUND: Arteriovenous malformation (AVM) compartments are thought as
      independently fed, hemodynamically independent components of the AVM nidus. Its
      possible role in modulating transnidal pressures have not been investigated to
      our knowledge. OBJECTIVE: To investigate if AVM compartments play a role in
      modulating transnidal pressures by using electrical models as a method of
      investigation. MATERIALS AND METHODS: Monocompartmental and multicompartmental
      AVM models were constructed using electrical circuits- building on Dr.
      Guglielmi's previous work. Each compartment was fed by two feeding arteries
      (resistors) and had a shared draining vein with other compartments in the AVM
      nidus. Each compartment is composed of a series of resistors which represents the
      pressure gradient along the AVM (arterial, arteriolar, venular, and venous).
      Pressure (voltage) readings were obtained within these nidal points. RESULTS: The
      pressure gradient (venous-arterial) is more as there are less AVM compartments in
      the nidus model. The monocomparmental model had a pressure gradient of 66mmHg
      (V); while it was 64, 61, and 59 for the 2-, 3-, and 4-compartment models,
      respectively. In addition, the more the number of compartments, the greater the
      flow (mA) is in the whole AVM nidus, 33 ml/min for the monocompartmental AVM and
      121ml/min for the 4-compartment AVM; though there was greater flow per
      compartment as there were less compartments, 33ml/min per compartment for the
      monocompartmental model versus 29ml/min for the 4-compartment model. CONCLUSION:
      Transnidal pressure gradients may be less the more compartments an AVM has. This
      electrical model represents an approach that can be used in investigating the
      hemodynamic contributions of AVM compartments.

PMID- 23559985
TI  - Five-year follow-up results for patients diagnosed with anaplastic astrocytoma
      and effectiveness of concomitant therapy with temozolomide for recurrent
      anaplastic astrocytoma.
AB  - BACKGROUND: Anaplastic astrocytoma (AA; WHO grade-III) patients determination of
      prognostic factors helps generating multimodal therapy protocols. For this
      purpose, in the Baskent University, Adana Medical Research Center, specific
      characteristics of AA patients who have surgery were retrospectively investigated
      and factors which affect prognosis has been determined. PATIENTS AND METHODS:
      Between January 2005 and 2009, 20 patients who have AA have been evaluated
      retrospectively. Totally, 20 patients had 31 operations. Sixteen patients had
      only adjuvant radiation therapy (RT). In the postoperative period, 8 patients
      received adjuvant RT. Nine of 10 patients with tumor recurrence received
      concomitant therapy with temozolomide (ConcT with TMZ) protocol. No adjuvant
      therapy protocol could be applied in three patients with poor general condition
      in the postoperative period. RESULTS: Median survival for patients died was 16+/
      17 months; one year survival was 75% and five year survival 25%. After univariate
      analysis, preoperative Karnofsky performance score (KPS) was >=80
      (P=0.005577(*)), postoperative KPS was >=80 (P=0.003825(*)), type of tumor
      resection (P=0.001751(*)), multiple operations (P=0.006233(*)), and ConcT with
      TMZ protocol (P=0,005766(*)) were all positive prognostic factors which extend
      the survival. CONCLUSIONS: The results of the multivariate analysis did not put
      forward an independent prognostic factor acting on the survival period (P>0.05).

PMID- 23559986
TI  - Results of surgical excision of cirsoid aneurysm of the scalp without
      preoperative interventions.
AB  - CONTEXT: Cirsoid aneurysms of scalp are rare lesions which are mainly treated by
      surgical excision. Endovascular embolization was described either alone or prior
      to surgery in order to minimize the risk of bleeding. However, the endovascular
      therapy also carries the risk of scalp necrosis, escape of embolization material
      to circulation, and recurrence of the lesion. AIM: To evaluate the results of
      well-planned classic surgical excision of cirsoid aneurysm. STUDY DESIGN: This is
      a retrospective case series study. MATERIALS AND METHODS: This is a retrospective
      case series study on nine patients with cirsoid aneurysms who were treated with
      surgical excision. Preoperative Planning for location, size, feeding arteries,
      and venous drainage of the lesions were done by plain and contrast enhanced CT,
      MRI, MR angiogram, and selective internal and external carotid angiograms.
      Complete surgical excision for the lesions was done. Postoperative evaluation of
      excision was done by cranial magnetic resonance angiography in all the patients.
      The mean follow up period was 34.1 (+/-7.62 STD) months. RESULTS: The lesion was
      located in the occipital region in three (33.3%) cases, frontal region in two
      (22.2%) cases, temproparietal region in two (22.2%) cases, parietal region in one
      case (11.1%), and vertex in one case (11.1%). The superficial temporal artery was
      involved in seven (77.8%) cases, the occipital artery was involved in six (66.7%)
      cases, the posterior auricular artery was involved in five (55.6%) cases, the
      supraorbital artery was involved in two (22.2%) cases and the middle meningeal
      artery was involved in two (22.2%) cases. Total excision of the lesion was
      achieved in eight patients and en bloc resection and primary closure was done in
      one patient. Postoperative magnetic resonance angiogram showed no residual lesion
      in all patients. No postoperative complication related to the surgery had
      occurred. No recurrence had occurred during the follow-up period (mean 34.1 +/-
      7.62 STD months). CONCLUSION: Well-planned surgery of cirsoid aneurysm of the
      scalp without preoperative interventions could achieve complete excision of the
      lesion without any residual masses or recurrence and with a low incidence of
      complications.

PMID- 23559987
TI  - Primary intracranial germ cell tumors.
AB  - BACKGROUND: Primary intracranial germ cell tumors are rare (ICGCTs) and usually
      localized in the pineal and suprasellar regions of the brain. They are divided
      into histologic types: Germinoma, teratoma choriocarcinoma, embryonal carcinoma,
      yolk sac tumor, and malignant mixed germ cell tumors (MMGCTs). Neuroimaging
      evaluation is useful to distinguish between the types of ICGCTs. Germinoma is
      highly sensitive to radiotherapy or/and chemotherapy, and is potentially curable
      without surgery. MMGCTs are treated with the combination of chemotherapy and
      radiation, with a poorer prognosis. ICGCTs warrant correct pre-operative
      diagnosis in order to decide on appropriate management. AIM: To report the
      clinicopathological and immunohistochemical findings in three cases of primary
      intracranial germ-cell tumor. MATERIALS AND METHODS: Three cases of intracranial
      germ cell tumors inclusive of both genders and all brain regions were retrieved
      from the archives of the Anatomical Pathology Department at King Abdul Aziz
      University Hospital, Jeddah between the years, 1995-2011, through a computerized
      search. RESULTS: Based on histological examination, they were respectively
      diagnosed as MMGCTs (two cases) and germinoma. Clinical, radiological,
      pathological characteristics and immunohistochemical profile of the three ICGCTs
      are presented along with the review of recent literature. CONCLUSION: ICGCTs are
      rare tumors affecting males more than females, and at the end of three years
      follow-up in the present study, treatment morbidity appears to be low with no
      recurrence observed among surviving patients, indicating that suprasellar and
      basal ganglia ICGCTs may have a favorable prognosis regardless of histological
      type. Pineal MMGCTs may have an aggressive course.

PMID- 23559988
TI  - Extracranial-intracranial bypass of the bilateral anterior cerebral circulation
      using a thoracodorsal axis artery-graft.
AB  - Bilateral extracranial-intracranial (EC-IC) bypass-grafting of the cerebral
      circulation is uncommon. We report a case of anterior cerebral artery EC-IC
      bypass using the thoracodorsal axis artery-graft. The bifurcation of the
      thoracodorsal axis allows bypass of both anterior hemispheres, while matching
      appropriate small-vessel dimensions.

PMID- 23559989
TI  - Delayed radiation myelopathy: Differential diagnosis with positron emission
      tomography/computed tomography examination.
AB  - Myelopathy is a rare but serious complication of radiation therapy (RT).
      Radiation myelopathy is white matter damage to the spinal cord developed after a
      certain period of application of ionizing radiation. Factors such as radiation
      dose and time between applications affect the occurrence as well as the severity
      of myelopathy. In those patients, positron emission tomography/computed
      tomography examination has a very important role both in the diagnosis and in the
      differential diagnosis of lesions. In this case report, the case of progressive
      paraparesis, developed in a 52-year-old female patient operated with pulmonary
      mucinous cystadenocarcinoma diagnosis and who received chemotherapy and RT
      following surgery, has been reported.

PMID- 23559991
TI  - Tongue swelling and necrosis after brain tumor surgery.
AB  - We present a case of tongue necrosis due to intraoperative pressure injury. A
      laryngeal mask airway with adhesive electrodes was inserted into the oropharynx,
      over an endotracheal tube, to facilitate glossopharyngeal nerve monitoring during
      craniotomy for a cerebellopontine angle tumor. The case, mechanisms of injury,
      and modifications to our current practice are discussed.

PMID- 23559990
TI  - Traumatic epidural and subdural hematomas and extensive brain infarcts in a
      patient with pial arteriovenous malformation: Mechanisms underlying clinical and
      radiological findings.
AB  - We report a rare case of a patient with a pial arteriovenous malformation (AVM)
      who presented in altered sensorium. He was found to have large epidural and
      subdural hematomas overlying a pial AVM. He underwent evacuation of these
      hematomas and postop computed tomography showed infarcts deep to the site of
      hematoma evacuation. These infarcts were postulated to be due to a steal
      phenomenon combined with raised intracranial pressure. The management and
      possible mechanisms for this rare combination are discussed.

PMID- 23559992
TI  - Melanotic cyst of L5 spinal root: A case report and review of literature.
AB  - Till date, 85 cases of melanotic schwannoma and 11 cases of spinal root melanoma
      have been reported in literature. We are reporting a case of a 45-year-old lady
      who presented with primary low back pain, and magnetic resonance imaging of lumbo
      sacral spine showed at left L5-S1 foraminal lesion extending to the para-spinal
      compartment. Hemi-laminectomy, facetectomy, and excision of the lesion were done.
      It was primarily a cystic lesion with attachment to the exiting spinal nerve
      root. Histopathology of the cyst wall showed a fibro-collagenous stroma with no
      specific cell lining containing melanin pigment suggestive of a melanotic cyst.
      The patient was completely relieved of the back pain, and had no recurrence over
      a follow-up period of one and half years. This case is probably the first
      reported predominantly cystic, pigmented lesion, affecting the spinal root.

PMID- 23559993
TI  - Giant cavernous hemangiomas of the brain.
AB  - Cavernous angiomas or hemangiomas or cavernomas are benign, vascular
      malformations of the central nervous system and classified as occult vascular
      brain lesions, usually present in adulthood. With the advent of computed
      tomography and magnetic resonance imaging, these lesions are increasingly
      recognized in children. We report two cases of pediatric brain cavernomas where
      the children presented with recurrent seizures. Imaging findings were suggestive
      of giant cavernous hemangioma. The lesions were excised completely and the
      patients recovered well without deficits with good control of seizures.

PMID- 23559994
TI  - A rare case of intramedullary tuberculoma: Complete resolution after medical
      treatment and role of magnetic resonance imaging in diagnosis and follow-up.
AB  - Intramedullary tuberculoma (IMT) is a rare form of spinal tuberculosis. IMT has
      an incidence of 2 cases per 2000 cases of central nervous system tuberculosis.
      Magnetic resonance imaging (MRI) can be helpful for diagnosing IMT at an early
      stage and it is also very useful in follow-up. Three stages of IMT have been
      described in MRI based on the evolution of the lesion. Medical therapy is the
      mainstay of treatment for IMT though there are surgical options for select
      patients. Here, we describe a patient with dorsal IMT who improved clinically as
      well as radiologically with antituberculous treatment and steroids.

PMID- 23559995
TI  - Air embolism related to removal of Mayfield head pins.
AB  - Venous air embolism (VAE) may be fatal and frequently carries high neurologic,
      respiratory, and cardiovascular morbidity. Its occurrence during anesthesia is
      challenging to the anesthesiologists in terms of early discovery and management.
      VAE during neurosurgical procedures especially in the sitting position is well
      known and usually prepared for it; however, VAE might happen unexpectedly as in
      this patient's case. A young patient underwent an exploratory pterional
      craniotomy for recollection of subdural hematoma and head pins were used to
      stabilize the head. The surgery and anesthesia were uneventful; however, he
      developed a sudden cardiovascular collapse at the end of surgery and immediately
      after removal of the Mayfield pins.

PMID- 23559996
TI  - Pearl in interhemispheric fissure: A rare phenomenon.
AB  - Epidermoid cysts (Keratin pearls) are benign congenital lesions, found commonly
      in cerebello-pontine angle, suprasellar cistern, sylvian cistern, pineal region,
      but they are very rare in interhemispheric fissure. Approaching these lesions are
      challenging to neurosurgeons because of narrow and deep fissure with surrounding
      vital structures. The present study constitutes an analysis of interhemispheric
      epidermoid managed at our hospital in last 10 years (Jan 2001-Dec 2010). Total
      187 cases of intracranial epidermoid operated in our institute; eight of them
      were interhemispheric epidermoid making about 4.27% of all epidermoids. The
      patients were presented with seizures (50%), headache (37%), and weakness (25%).
      On examination, the common findings were decreased Mini mental score (MMSE) in
      50%, motor deficit in 25%, and decreased visual acuity in 25% of cases. All
      patients underwent craniotomy across the midline as per the location of the
      lesions. In seven patients, tumors were resected by interhemispheric approach but
      in one by transcortical. Lesion were excised with microscope and endoscopic
      assistance with measures to prevent spillage of epidermoid tissue while excision.
      Post excision tumor bed was irrigated with hydrocortisone diluted saline. All
      patients except one improved after surgery and non-developed chemical meningitis.
      One patient of parietal interhemispheric epidermoid with transcortical approach
      developed weakness in immediate post-operative period. Patients were followed for
      average 6.8 year without any recurrence. Interhemispheric epidermoids are rare
      tumors. Achieving safe complete excision without spillage is surgical goal to
      prevent chemical meningitis and recurrence. Endoscope assists in achieving
      complete excision so decrease incidence of chemical meningitis and recurrence.

PMID- 23559997
TI  - Abdominal epilepsy in chronic recurrent abdominal pain.
AB  - BACKGROUND: Abdominal epilepsy (AE) is an uncommon cause for chronic recurrent
      abdominal pain in children and adults. It is characterized by paroxysmal episode
      of abdominal pain, diverse abdominal complaints, definite electroencephalogram
      (EEG) abnormalities and favorable response to the introduction of anti-epileptic
      drugs (AED). We studied 150 children with chronic recurrent abdominal pain and
      after exclusion of more common etiologies for the presenting complaints; workup
      proceeded with an EEG. We found 111 (74%) children with an abnormal EEG and 39
      (26%) children with normal EEG. All children were subjected to AED
      (Oxcarbazepine) and 139 (92%) children responded to AED out of which 111 (74%)
      children had an abnormal EEG and 27 (18%) had a normal EEG. On further follow-up
      the patients were symptom free, which helped us to confirm the clinical
      diagnosis. CONTEXT: Recurrent chronic abdominal pain is a common problem
      encountered by pediatricians. Variety of investigations are done to come to a
      diagnosis but a cause is rarely found. In such children diagnosis of AE should be
      considered and an EEG will confirm the diagnosis and treated with AED. AIMS: To
      find the incidence of AE in children presenting with chronic recurrent abdominal
      pain and to correlate EEG findings and their clinical response to empirical AEDs
      in both cases and control. SETTINGS AND DESIGN: Krishna Institute of Medical
      Sciences University, Karad, Maharashtra, India. Prospective analytical study.
      MATERIALS AND METHODS: A total of 150 children with chronic recurrent abdominal
      pain were studied by investigations to rule out common causes of abdominal pain
      and an EEG. All children were then started with AED oxycarbamezepine and their
      response to the treatment was noted. RESULTS: 111 (74%) of the total 150 children
      showed a positive EEG change suggestive of epileptogenic activity and of which 75
      (67.56%) were females and 36 (32.43%) were male, majority of children were in the
      age of group of 9-12 years. Temporal wave discharges were 39 (35.13%) of the
      total abnormal EEG's. All the children were started on AEDs and those with
      abnormal EEG showed 100% response to treatment while 27 (18%) children with
      normal EEG also responded to treatment. Twelve (8%) children did not have any
      improvement in symptoms. CONCLUSIONS: A diagnosis of AE must be considered in
      children with chronic recurrent abdominal pain, especially in those with
      suggestive history, and an EEG can save a child from lot of unnecessary
      investigations and suffering.

PMID- 23559998
TI  - Split cord malformation with dorsally located bony spur: Report of four cases and
      review of literature.
AB  - Split cord malformations (SCM) with a dorsally located bony spur are a very rare
      entity. The authors report a series of four such cases. The literature is
      reviewed regarding the pathogenesis and management of this uncommon variant of
      SCM. The presenting features include - scoliosis with motor and autonomic
      dysfunction (n = 1), scoliosis with cutaneous patch (n = 1), hypertrichotic area
      (n = 1), and motor deficits alone (n = 1). The location of spur was thoracic and
      lumbar in two patients (50%) each. Low-lying conus was present in three patients.
      Long segment syrinx was present in one patient. With respect to the bony
      anomalies, two patients had a hypertrophied posterior arch (HPA) and one patient
      had a dysraphic spine. All patients underwent surgical excision of the spur with
      detethering, if a low-lying conus was present. Two patients developed transient
      worsening of the neurological status after surgery which recovered at the time of
      the last follow-up; in both these patients, there was a HPA and a low-lying
      conus. Surgical excision of the spur with detethering of filum, in cases of low
      lying conus, is the treatment of choice. Risk of post-operative worsening of the
      neurological status is increased in cases in which there is concomitant presence
      of HPA.

PMID- 23559999
TI  - Effective dose of topiramate in pediatric migraine prophylaxis.
AB  - OBJECTIVE: Migraine is a common neurological disorder in childhood and
      adolescence. Topiramate is a new anticonvulsant drug, recently being used in
      migraine prophylaxis in adults, although it is not approved by the Food and Drug
      Administration for prevention of pediatric migraine. The present study was
      planned and performed to evaluate the efficacy of low-dose topiramate in
      pediatric migraine prophylaxis. MATERIALS AND METHODS: A prospective study,
      including 60 patients with migraine headaches was performed for a period of two
      months. The patients were randomly divided into two treatment groups - treated by
      topiramate < 2 mg/kg/day and > 2 mg/kg/day. All the patients were evaluated at 0,
      4, and 8 weeks of the study for the clinical response. RESULTS: The patients
      receiving topiramate < 2 mg/kg/day (mean dose of 1.2 +/- 0.7 mg/kg/day) showed a
      reduction in the mean (+/-SD) of migraine frequency from 6.2 (+/-2.4) to 3.0 (+/
      1.8) episodes per month, headache intensity from 7.2 (+/-1.95) to 3.7 (+/-1.8)
      based on the Visual Analog Scale, and headache duration from 5.4 (+/-2.1) to 2.2
      (+/-1.3) h. In the patients treated with topiramate > 2 mg/kg/day (mean dose of
      2.4 +/- 0.5 mg/kg/day), the mean (+/-SD) of monthly headache frequency reduced
      from 6.9 (+/-2.1) to 3.24 (+/-1.2) per month, intensity from 7.11 (+/-1.4) to
      3.14 (+/-2.41), and headache duration from 5.2 (+/-2.4) to 1.8 (+/-1.2) h, at the
      end of follow-up (P > 0.05). The most common side effects of topiramate were
      paresthesias (five patients), anorexia (four patients), drowsiness (four
      patients). CONCLUSION: The results of this study demonstrated that low-dose of
      topiramate (<2 mg/kg/day) is effective, well-tolerated, safe, and suggested as an
      alternative prophylactic treatment for pediatric migraine.

PMID- 23560000
TI  - Muscular myopathies other than myotonic dystrophy also associated with (CTG)n
      expansion at the DMPK locus.
AB  - OBJECTIVE: Assess triplet repeat expansion (CTG)n at the 'dystrophia-myotonica
      protein kinase' (DMPK) locus in muscular myopathies to elucidate its role in
      myopathic symptoms and enable genetic counseling and prenatal diagnosis in
      families. METHODS AND RESULTS: Individuals with symptoms of myopathy, hypotonia
      and controls selected randomly from the population were evaluated for triplet
      repeat expansion of (CTG)n repeats in the 3'untranslated region (UTR) of DMPK
      gene, the causative mutation in myotonic dystrophy (DM). DNA was isolated from
      peripheral blood of 40 individuals; they presented symptoms of muscle myopathy (n
      = 11), muscle hypotonia (n = 4), members of their families (n = 5) and control
      individuals from random population (n = 20). Molecular analysis of genomic DNA by
      polymerase chain reaction (PCR) using primers specific for the DMPK gene
      encompassing the triplet repeat expansion, showed that all controls (n = 20) gave
      a 2.1 kb band indicating normal triplet repeat number. Three out of 11 cases (two
      clinically diagnosed DM and one muscular dystrophy) had an expansion of the
      (CTG)n repeat in the range of 1000-2100 repeats corresponding to the repeat
      number in cases of severe DM. Other two of these 11 cases, showed a mild
      expansion of ~ 66 repeats. Three samples, which included two cases of hypotonia
      and the father of a subject with muscular dystrophy, also gave a similar repeat
      expansion (~66 repeats). CONCLUSION: Results suggest a role of (CTG)n expansion
      at the DMPK locus in unexplained hypotonias and muscular myopathies other than
      DM. This calls for screening of the triplet repeat expansion at the DMPK locus in
      cases of idiopathic myopathies and hypotonia.

PMID- 23560001
TI  - GM1gangliosidosis: Clinical and radiological clue to diagnosis.
AB  - GM1gangliosidosis is a rare autosomal recessive lysosomal storage disorder caused
      by deficiency of enzyme beta-galactosidase, resulting in progressive neural and
      visceral accumulation of GM1gangliosides. Coarse facial features, bilateral
      cherry red spots, and dysostosis multiplex are important clue to diagnose this
      condition. We describe a case of GM1gangliosidosis with dysostosis multiplex and
      characteristic magnetic resonance imaging findings.

PMID- 23560002
TI  - Neurocristic cutaneous hamartoma of the scalp.
AB  - Neurocristic cutaneous hamartoma of the scalp, a rare entity, may be either
      congenital or acquired. The former must be distinguished from other forms of
      congenital nodular and plaque-like lesions such as giant congenital nevi, common
      and cellular blue nevi, and melanoma. We describe the clinicopathologic features
      of an example occurring in a 2-month-old girl presenting with a large
      parietooccipital swelling. The literature is reviewed.

PMID- 23560003
TI  - Acalvaria: A rare congenital malformation.
AB  - Acalvaria is described as a rare congenital malformation in a 1-month-old female
      baby who presented with classical clinical features of soft, lax skull as a
      result of absent skull bones and associated muscles. Acalvaria is usually a fatal
      anomaly and is rarely discussed in English literature. Thus, we herein report a
      living case of acalvaria along with a review of the literature.

PMID- 23560005
TI  - Scoliotic deformity and asymptomatic cervical syrinx in a 9 year old with caudal
      regression syndrome.
AB  - We report late presentation of caudal regression syndrome in a 9 year old
      presenting with a scoliotic deformity. She in addition had an asymptomatic
      cervical syrinx and vitiligo. We discuss the reasons for this unusual
      constellation of symptomatology present in our case.

PMID- 23560004
TI  - Neurenteric cyst of the ventral cervicomedullary region.
AB  - Neurenteric cysts are rare, benign, endodermally derived tumors of the central
      nervous system. Intracranial neurenteric cysts are rare with posterior fossa
      being the most common location among them. Neurenteric cyst of the craniocervical
      region is very rare. Authors report a rare case of neurenteric cyst located in
      the ventral cervicomedullary region. The pertinent literature is reviewed
      regarding this uncommon entity.

PMID- 23560006
TI  - Spinal cord involvement in a child with familial hemophagocytic
      lymphohistiocytosis.
AB  - The involvement of the central nervous system (CNS) in familial hemophagocytic
      lymphohistiocytosis (FHL) has known to be limited to the brain, brain stem, and
      cerebellum. Herein, we report an 11-year-old boy who presented with neurological
      symptoms and was diagnosed as FHL by molecular diagnosis. The hemophagocytic
      lesions in the CNS were shown to extend to the thoracal level of spinal cord
      which completely disappeared after the completion of hemophagocytic
      lymphohistiocytosis-2004 protocol.

PMID- 23560007
TI  - Heterogeneity in spinal muscular atrophy with respiratory distress type 1.
AB  - Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a clinically
      heterogeneous disorder linked to mutations in the immunoglobulin mu-binding
      protein 2 (IGHMBP2) gene on chromosome 11q13-q21. Most infants with SMARD1
      present between six weeks and six months of age with respiratory distress
      secondary to diaphragmatic weakness and progressive distal weakness. Sensory and
      autonomic dysfunctions sometimes accompany the motor weakness. This report
      describes a male infant with genetically confirmed SMARD1 presenting with onset
      of disease in the first two weeks of life with respiratory compromise and urinary
      retention, which has not been reported before and adds to the phenotypic
      variability of SMARD 1.

PMID- 23560008
TI  - Multiple cerebral cavernous haemangiomas in an infant.
AB  - Cerebral cavernous malformations (CCMs) are vascular malformations causing
      seizures and cerebral hemorrhages. We report a 20-month old male with multiple
      CCMs associated with Krev interaction trapped 1 (KRIT1) c.845 + 1 G > C
      heterozygous transversion mutation. This case demonstrates the importance of
      molecular genetic analysis in cases of multiple CCM.

PMID- 23560009
TI  - Precocious puberty due to human chorionic gonadotropin secreting germinoma.
AB  - This study aims to report a rare case of precocious puberty (PP) due to a human
      chorionic gonadotropin (hCG)-producing germinoma located in the suprasellar
      region. A 10-year-old male patient presented with sexual precocity, headache,
      drowsiness, loss of appetite, and papilledema. Significant acceleration of bone
      age in relation to chronological age, high serum total testosterone levels, and
      hypopituitarism (unresponsiveness to stimulation test) were observed. Magnetic
      resonance imaging (MRI) of the brain showed a large suprasellar tumor and
      triventricular dilatation. High hCG levels were found in both blood and
      cerebrospinal fluid. Hormone replacement therapy and transcranial surgery
      associated with radiotherapy were performed, with complete regression of sexual
      characteristics and normal laboratory tests post-operatively. Clinical and
      laboratory findings, in addition to MRI scans, led to the diagnosis of an hCG
      producing tumor and PP, which represents a rare report in the literature.

PMID- 23560010
TI  - Lateral intraventricular epidermoid in a child with hydrocephalus.
AB  - Lateral intraventricular tumors are uncommon. They grow linearly rather than
      exponentially and hence are slow-growing lesions without causing mass effects and
      hydrocephalus. We report a rare case of large bulky right intraventricular
      epidermoid tumor in a child. This tumor was associated with mass effect on the
      surrounding structures and hydrocephalus.

PMID- 23560011
TI  - Intracerebral metastasis in pediatric acute lymphoblastic leukemia: A rare
      presentation.
AB  - Central nervous system leukemia may present in different ways. However,
      intraparenchymal mass is extremely rare in childhood leukemia. Herein, we report
      a boy who presented with right hemiparesis and anisocoria 1 year after the
      cessation of the chemotherapy protocol for acute lymphoblastic leukemia. Cranial
      imaging demonstrated an extensive mass located in the anterior white matter of
      left frontal lobe, and cerebrospinal fluid examination revealed concomitant
      lymphoblasts. Immunohistochemical staining of the biopsy material showed
      neoplastic cells with positive CD10 and TdT. Complete remission was achieved with
      chemotherapy alone for a duration of 2 years.

PMID- 23560012
TI  - Chondromyxoid fibroma of the temporal bone: A rare entity.
AB  - Chondromyxoid fibroma (CMF) is the least common benign tumor of the cartilaginous
      origin. It is very unusual to find these tumors in the skull bones. We report one
      such case involving the temporal bone. Till date, only nine such cases including
      this patient, involving the temporal bone have been reported to the best of our
      knowledge. Grant Medical College and Sir J.J Group of Hospitals, Byculla, Mumbai,
      Maharashtra, India. A 12-year-old female patient presented with a history of
      headache associated with left earache of 1 month duration. This was followed by
      swelling over the left preauricular region 15 days later. Imaging was suggestive
      of an expansile lesion involving the squamous part of the left temporal bone with
      calcifications suggestive of a benign chondroid lesion. The patient was operated
      upon with left temporal incision and complete excision of the lesion. The patient
      had relief from headache, earache and swelling, with no evidence of new
      neurological deficit in the post-operative period. CMF of the skull bone is an
      extremely rare tumor. Differential diagnosis should be kept in mind, especially
      in cases of calcified lesions and includes chordoma, chondroid chondroma, and low
      grade myxoid chondrosarcoma. En-bloc complete excision should be the aim to
      achieve cure.

PMID- 23560013
TI  - Superficial siderosis: A rare occurrence in children.
AB  - Superficial siderosis of the central nervous system results from deposition of
      hemosiderin in the subpial layers of the brain and spinal cord. Patients usually
      present after 40 years of age with progressive ataxia and sensorineural hearing
      impairment. We present the case of a twelve-year-old boy who had a surgery of the
      posterior fossa at the age of two years and then developed recurrent headaches,
      instability of gait, and hearing deficit at around ten years of age. Clinical
      examination revealed progressive ataxia and mild sensorineural hearing loss. He
      also had infrequent seizures with mild electroencephalographic abnormality. His
      serial magnetic resonance imaging (MRIs) showed a progressive deposition of
      hemosiderin in the cerebellar folia and around the brainstem, confirming a
      diagnosis of superficial siderosis. This case report draws attention to this rare
      condition, usually seen in adults, even though rarely it can be seen in children
      as a chronic sequela of surgery of the posterior fossa.

PMID- 23560014
TI  - Sacrococcygeal myxopapillary ependymoma with anaplastic ependymoma component in
      an infant.
AB  - Sacrococcygeal location of myxopapillary ependymoma (MPE) is uncommon. Local
      recurrence and metastases are on record inspite of its benign characteristics. We
      report a rare case of sacrococcygeal MPE in an 11-month-old female child who
      showed typical myxopapillary ependymal histology along with anaplastic ependymal
      component. Ki-67 labeling index in the myxopapillary component was 4-5% and in
      the anaplastic component was 70%. Six weeks after gross total resection of the
      tumor, the child presented with local recurrence and metastasis in the right
      inguinal lymph nodes and was treated with chemotherapy. The present case of
      sacrococcygeal MPE with anaplastic ependymoma component is the second case on
      record in the medical literature, and the first case without any syndromic
      features. Metastasis in this case can be explained because of the anaplastic
      component, with mitotic count of 5-6/high power field and high Ki-67 labeling
      index.

PMID- 23560015
TI  - Posterior reversible encephalopathy syndrome in a child with autoimmune
      lymphoproliferative syndrome: Case report and review of literature.
AB  - Posterior reversible encephalopathy syndrome (PRES) is characterized by headache,
      nausea, vomiting, seizures and visual disturbances. PRES has been usually
      associated with hypertension, chronic renal disease, malignancy and
      chemotherapeutic agents. We report the association of PRES with Autoimmune
      lymphoproliferative syndrome, which to our best knowledge has not been reported
      before.

PMID- 23560016
TI  - Phrenic nerve palsy: A rare cause of respiratory distress in newborn.
AB  - Birth injury is defined as an impairment of a newborn's body function or
      structure due to adverse influences that occurred at birth. Phrenic nerve palsy
      may result from birth trauma during a traumatic neonatal delivery from a stretch
      injury due to lateral hyperextension of the neck at birth. This could be a rare
      cause of respiratory distress in the newborn period with irregular respiration.
      Respiratory distress due to phrenic nerve damage leading to paralysis of the
      ipsilateral diaphragm may require continuous positive airway pressure or
      mechanical ventilation and if unresponsive, surgical plication of diaphragm.
      Herein, we report a case of phrenic nerve palsy in a newborn presenting with
      respiratory distress.

PMID- 23560017
TI  - Spontaneous extrusion of peritoneal catheter of ventriculoperitoneal shunt
      through the intact abdominal wall: Report of two cases.
AB  - Among the various complications associated with ventriculoperitoneal shunt (VPS)
      surgery, migration of the peritoneal catheter is one of the rarest complications.
      We report two cases of spontaneous extrusion of the peritoneal portion of the VPS
      through the intact abdominal wall at an area unrelated to the surgical incision.
      Both were conscious and had no neurological deficits. There were no signs of
      infection. The peritoneal end of the shunt was removed through the abdomen. Shunt
      revision was performed. The patients were discharged 8 days after the revision
      without any complications. At 6-month follow-up, both of them are doing well.
      Possible mechanisms of abdominal wall perforation are discussed. Pulling the
      extruded peritoneal end through abdominal wall decreases the possibility of
      infection and is probably the best way of management.

PMID- 23560018
TI  - Motor aphasia: A rare complication of scorpion sting.
AB  - Scorpion sting is common in villages, and is an important public health problem
      in India. The clinical symptoms of envenomation by scorpion sting are by
      sympathetic and parasympathetic stimulation, causing a variety of symptoms. The
      leading causes of death are cardiac dysfunction and pulmonary edema. We present
      herein a case of scorpion sting in a 9-year-old boy who developed pulmonary edema
      and gradually developed cytotoxic cerebral edema with infarct leading to motor
      aphasia with upper motor neuron facial palsy.

PMID- 23560019
TI  - Unilateral open-lip schizencephaly: A rare cause of infantile hemiparesis.

PMID- 23560020
TI  - Rhombencephalo-synapsis with turricephaly.

PMID- 23560021
TI  - Juvenile anaplastic hemangiopericytoma of cavernous sinus.

PMID- 23560022
TI  - A rare cause of congenital ptosis: Blepharophimosis, ptosis and epicanthus
      inversus syndrome.

PMID- 23560023
TI  - Perioperative management of a hemophilia B infant with intracranial hemorrhage.

PMID- 23560024
TI  - Concurrent infection of Japanese encephalitis and mixed plasmodium infection.

PMID- 23560025
TI  - Author reply.

PMID- 23560026
TI  - Aseptic meningitis following intravenous immunoglobulin therapy of common
      variable immunodeficiency.

PMID- 23560027
TI  - Author reply.

PMID- 23560028
TI  - Fitting In: Segregation, Social Class, and the Experiences of Black Students at
      Selective Colleges and Universities.
AB  - We analyzed qualitative data gathered at a selective urban university with a
      large black student body. We found that black students from integrated
      backgrounds welcomed the chance to establish friendships with same-race peers
      even though they were at ease in white settings, whereas students from segregated
      backgrounds saw same-race peers as a source of comfort and refuge from a white
      world often perceived as hostile. These contrasting perceptions set up both
      groups for shock upon matriculation. Students from an integrated background were
      better prepared academically and socially, but were unfamiliar with urban black
      culture and uncomfortable interacting with students of lower class standing.
      Students from a segregated background were surprised to find they had little in
      common with more affluent students from integrated backgrounds. Although both
      groups were attracted to campus for the same reason-to interact with a critical
      mass of same-race peers-their contrasting expectations produced a letdown as the
      realities of intraracial diversity set in.

PMID- 23560029
TI  - Mechanisms of resistance in bacteria: an evolutionary approach.
AB  - Acquisition of resistance is one of the major causes of failure in therapy of
      bacterial infections. According to the World Health Organization (WHO), thousands
      of deaths caused by Salmonella sp., Escherichia coli, Staphylococcus aureus or
      Mycobacteria tuberculosis are due to failure in therapy caused by resistance to
      the chemotherapeutic agents. Understanding the mechanisms of resistance
      acquisition by the bacterial strains is therefore essential to prevent and
      overcome resistance. However, it is very difficult to extrapolate from in vitro
      studies, where the variables are far less and under constant control, as compared
      to what happens in vivo where the chosen chemotherapeutic, its effective dose,
      and the patient's immune system are variables that differ substantially case-by
      case. The aim of this review is to provide a new perspective on the possible ways
      by which resistance is acquired by the bacterial strains within the patient, with
      a special emphasis on the adaptive response of the infecting bacteria to the
      administered antibiotic.

PMID- 23560030
TI  - Pimozide Inhibits the AcrAB-TolC Efflux Pump in Escherichia coli.
AB  - Efflux pump inhibitors (EPIs) are attractive compounds to reverse multidrug
      resistance in clinically relevant bacterial pathogens. In this study we tested
      the ability of the neuroleptic drug pimozide to inhibit the Escherichia coli
      AcrAB-TolC efflux pump, whose overproduction confers resistance to various
      antimicrobial agents. A real-time Nile red efflux assay in the AcrAB -
      overproducing strain 3-AG100 revealed that pimozide was capable of full
      inhibition of this pump at a concentration of 100 uM, which is far below its
      intrinsic MIC (>1mM). However, MIC assay demonstrated very little effect of
      pimozide with regard to reduction in MICs of various antimicrobial compounds.
      Only oxacillin MICs were reduced twofold in the presence of pimozide at 100 and
      200 uM. Since pimozide did considerably enhance accumulation of ethidium bromide
      in a fluorescence assay, ethidium bromide MIC assays in the presence and absence
      of this putative EPI were performed. They revealed that pimozide was able to
      reduce the MICs of ethidium bromide by 4-fold. In line with previous reports we
      suggest that the capability of EPIs to restore the susceptibility to
      antimicrobial agents can be highly substrate-specific due to different substrate
      binding sites.

PMID- 23560031
TI  - Correlation from undiluted vitreous cytokines of untreated central retinal vein
      occlusion with spectral domain optical coherence tomography.
AB  - PURPOSE: To correlate inflammatory and proangiogenic key cytokines from undiluted
      vitreous of treatment-naive central retinal vein occlusion (CRVO) patients with
      SD-OCT parameters. METHODS: Thirty-five patients (age 71.1 years, 24 phakic, 30
      nonischemic) underwent intravitreal combination therapy, including a single-site
      23-gauge core vitrectomy. Twenty-eight samples from patients with idiopathic, non
      uveitis floaterectomy served as controls. Interleukin 6 (IL-6), monocyte
      chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF
      A) levels were correlated with the visual acuity (logMar), category of CRVO
      (ischemic or nonischemic) and morphologic parameters, such as central macular
      thickness-CMT, thickness of neurosensory retina-TNeuro, extent of serous retinal
      detachment-SRT and disintegrity of the IS/OS and others. RESULTS: The mean IL-6
      was 64.7pg/ml (SD +/- 115.8), MCP-1 1015.7 ( +/- 970.1), and VEGF-A 278.4 ( +/-
      512.8), which was significantly higher than the control IL-6 6.2 +/- 3.4pg/ml
      (P=0.06), MCP-1 253.2 +/- 73.5 (P<0.0000001) and VEGF-A 7.0 +/- 4.9 (P<0.0006).
      All cytokines correlated highly with one another (correlation coefficient r=0.82
      for IL-6 and MCP-1; r=0.68 for Il-6 and VEGF-A; r=0.64 for MCP-1 and VEGF-A). IL
      6 correlated significantly with CMT, TRT, SRT, dIS/OS, and dELM. MCP-1 correlated
      significantly with SRT, dIS/OS, and dELM. VEGF-A correlated not with changes in
      SD-OCT, while it had a trend to be higher in the ischemic versus the nonischemic
      CRVO group (P=0.09). CONCLUSIONS: The inflammatory cytokines were more often
      correlated with morphologic changes assessed by SD-OCT, whereas VEGF-A did not
      correlate with CRVO-associated changes in SD-OCT. VEGF inhibition alone may not
      be sufficient in decreasing the inflammatory response in CRVO therapy.

PMID- 23560034
TI  - The occurrence of warfarin-related nephropathy and effects on renal and patient
      outcomes in korean patients.
AB  - BACKGROUND: Warfarin-related nephropathy (WRN) is a recently described disease
      entity, in which excessive warfarinization (international normalized ratio (INR)
      >3.0) causes acute kidney injury. Previous reports regarding WRN included few
      Asian patients who might have differed from the western WRN patients in terms of
      genetic and environmental factors. METHODS: During the period of March 2003 to
      December 2011, the data about a total of 1297 patients who had serum creatinine
      (sCr) level measured within 1 week after INR >3.0 and within 6 months before INR
      >3.0 was analyzed through the retrospective review of electronic medical records
      of a single tertiary hospital in Korea. RESULT: WRN developed in 19.3% of
      patients having excessive warfarinization. The incidence was higher in the
      chronic kidney disease (CKD) group than the non-CKD group. The risk of WRN
      increased as the basal serum albumin level decreased and was strongly associated
      with highest quartile serum AST level at post INR elevation and the presence of
      congestive heart failure. But the presence of atrial fibrillation was protective
      against the development of WRN. Neither the presence of CKD nor basal estimated
      glomerular filtration rate (eGFR) was an independent risk factor for WRN. Despite
      no difference in the basal sCr level, the sCr level was higher in patients with
      WRN than those without WRN after follow-up. The mortality rates were also higher
      in patients with WRN. CONCLUSIONS: WRN developed in 19.3% of patients having
      excessive warfarinization. A lower basal serum albumin, highest quartile serum
      AST level at post INR elevation, and congestive heart failure were associated
      with the occurrence of WRN. The development of WRN adversely affected renal and
      patient outcomes.

PMID- 23560033
TI  - Salivary microRNAs as promising biomarkers for detection of esophageal cancer.
AB  - BACKGROUND AND PURPOSE: Tissue microRNAs (miRNAs) can detect cancers and predict
      prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs
      share similar expression profiles. In this study, we investigated the
      discriminatory power of salivary miRNAs (including whole saliva and saliva
      supernatant) for detection of esophageal cancer. MATERIALS AND METHODS: By
      Agilent microarray, six deregulated miRNAs from whole saliva samples from seven
      patients with esophageal cancer and three healthy controls were selected. The six
      selected miRNAs were subjected to validation of their expression levels by RT
      qPCR using both whole saliva and saliva supernatant samples from an independent
      set of 39 patients with esophageal cancer and 19 healthy controls. RESULTS: Six
      miRNAs (miR-10b*, miR-144, miR-21, miR-451, miR-486-5p, and miR-634) were
      identified as targets by Agilent microarray. After validation by RT-qPCR, miR
      10b*, miR-144, and miR-451 in whole saliva and miR-10b*, miR-144, miR-21, and miR
      451 in saliva supernatant were significantly upregulated in patients, with
      sensitivities of 89.7, 92.3, 84.6, 79.5, 43.6, 89.7, and 51.3% and specificities
      of 57.9, 47.4, 57.9%, 57.9, 89.5, 47.4, and 84.2%, respectively. CONCLUSIONS: We
      found distinctive miRNAs for esophageal cancer in both whole saliva and saliva
      supernatant. These miRNAs possess discriminatory power for detection of
      esophageal cancer. Because saliva collection is noninvasive and convenient,
      salivary miRNAs show great promise as biomarkers for detection of esophageal
      cancer in areas at high risk.

PMID- 23560037
TI  - A discrete event simulation model for evaluating the performances of an m/g/c/c
      state dependent queuing system.
AB  - M/G/C/C state dependent queuing networks consider service rates as a function of
      the number of residing entities (e.g., pedestrians, vehicles, and products).
      However, modeling such dynamic rates is not supported in modern Discrete
      Simulation System (DES) software. We designed an approach to cater this
      limitation and used it to construct the M/G/C/C state-dependent queuing model in
      Arena software. Using the model, we have evaluated and analyzed the impacts of
      various arrival rates to the throughput, the blocking probability, the expected
      service time and the expected number of entities in a complex network topology.
      Results indicated that there is a range of arrival rates for each network where
      the simulation results fluctuate drastically across replications and this causes
      the simulation results and analytical results exhibit discrepancies. Detail
      results that show how tally the simulation results and the analytical results in
      both abstract and graphical forms and some scientific justifications for these
      have been documented and discussed.

PMID- 23560035
TI  - Lipidomic and spatio-temporal imaging of fat by mass spectrometry in mice
      duodenum during lipid digestion.
AB  - Intestinal absorption of dietary fat is a complex process mediated by enterocytes
      leading to lipid assembly and secretion of circulating lipoproteins as
      chylomicrons, vLDL and intestinal HDL (iHDL). Understanding lipid digestion is of
      importance knowing the correlation between excessive fat absorption and
      atherosclerosis. By using time-of-flight secondary ion mass spectrometry (TOF
      SIMS), we illustrated a spatio-temporal localization of fat in mice duodenum, at
      different times of digestion after a lipid gavage, for the first time. Fatty
      acids progressively increased in enterocytes as well as taurocholic acid,
      secreted by bile and engaged in the entero-hepatic re-absorption cycle. Cytosolic
      lipid droplets (CLD) from enterocytes were originally purified separating
      chylomicron-like, intermediate droplets and smaller HDL-like. A lipidomic
      quantification revealed their contents in triglycerides, free and esterified
      cholesterol, phosphatidylcholine, sphingomyelin and ceramides but also in free
      fatty acids, mono- and di-acylglycerols. An acyl-transferase activity was
      identified and the enzyme monoacylglycerol acyl transferase 2 (MGAT2) was
      immunodetected in all CLD. The largest droplets was also shown to contain the
      microsomal triglyceride transfer protein (MTTP), the acyl-coenzyme A-cholesterol
      acyltransferases (ACAT) 1 and 2, hormone sensitive lipase (HSL) and adipose
      triglyceride lipase (ATGL). This highlights the fact that during the digestion of
      fats, enterocyte CLD contain some enzymes involved in the different stages of the
      metabolism of diet fatty acids and cholesterol, in anticipation of the crucial
      work of endoplasmic reticulum in the process. The data further underlines the
      dual role of chylomicrons and iHDL in fat digestion which should help to
      efficiently complement lipid-lowering therapy.

PMID- 23560036
TI  - t-LSE: a novel robust geometric approach for modeling protein-protein interaction
      networks.
AB  - Protein-protein interaction (PPI) networks provide insights into understanding of
      biological processes, function and the underlying complex evolutionary mechanisms
      of the cell. Modeling PPI network is an important and fundamental problem in
      system biology, where it is still of major concern to find a better fitting model
      that requires less structural assumptions and is more robust against the large
      fraction of noisy PPIs. In this paper, we propose a new approach called t
      logistic semantic embedding (t-LSE) to model PPI networks. t-LSE tries to
      adaptively learn a metric embedding under the simple geometric assumption of PPI
      networks, and a non-convex cost function was adopted to deal with the noise in
      PPI networks. The experimental results show the superiority of the fit of t-LSE
      over other network models to PPI data. Furthermore, the robust loss function
      adopted here leads to big improvements for dealing with the noise in PPI network.
      The proposed model could thus facilitate further graph-based studies of PPIs and
      may help infer the hidden underlying biological knowledge. The Matlab code
      implementing the proposed method is freely available from the web site:
      http://home.ustc.edu.cn/~yzh33108/PPIModel.htm.

PMID- 23560038
TI  - Kinesin 5B (KIF5B) is required for progression through female meiosis and proper
      chromosomal segregation in mitotic cells.
AB  - The fidelity of chromosomal segregation during cell division is important to
      maintain chromosomal stability in order to prevent cancer and birth defects.
      Although several spindle-associated molecular motors have been shown to be
      essential for cell division, only a few chromosome arm-associated motors have
      been described. Here, we investigated the role of Kinesin 5b (Kif5b) during
      female mouse meiotic cell development and mitotic cell division. RNA interference
      (RNAi)-mediated silencing of Kif5b in mouse oocytes induced significant delay in
      germinal vesicle breakdown (GVBD) and failure in extrusion of the first polar
      body (PBE). In mitotic cells, knockdown of Kif5b leads to centrosome
      amplification and a chromosomal segregation defect. These data suggest that KIF5B
      is critical in suppressing chromosomal instability at the early stages of female
      meiotic cell development and mitotic cell division.

PMID- 23560039
TI  - High prevalence of tuberculosis and insufficient case detection in two
      communities in the Western Cape, South Africa.
AB  - BACKGROUND: In South Africa the estimated incidence of all forms of tuberculosis
      (TB) for 2008 was 960/100000. It was reported that all South Africans lived in
      districts with Directly Observed Therapy, Short-course. However, the 2011 WHO
      report indicated South Africa as the only country in the world where the TB
      incidence is still rising. AIMS: To report the results of a TB prevalence survey
      and to determine the speed of TB case detection in the study communities.
      METHODS: In 2005 a TB prevalence survey was done to inform the sample size
      calculation for the ZAMSTAR (Zambia South Africa TB and AIDS Reduction) trial. It
      was a cluster survey with clustering by enumeration area; all households were
      visited within enumeration areas and informed consent obtained from eligible
      adults. A questionnaire was completed and a sputum sample collected from each
      adult. Samples were inoculated on both liquid mycobacterium growth indicator tube
      (MGIT) and Lowenstein-Jensen media. A follow-up HIV prevalence survey was done in
      2007. RESULTS: In Community A, the adjusted prevalence of culture positive TB was
      32/1000 (95%CI 25-41/1000) and of smear positive TB 8/1000 (95%CI 5-13/1000). In
      Community B, the adjusted prevalence of culture positive TB was 24/1000 (95%CI 17
      32/1000) and of smear positive TB 9/1000 (95%CI 6-15/1000). In Community A the
      patient diagnostic rate was 0.38/person-year while in community B it was
      0.30/person-year. In both communities the adjusted HIV prevalence was 25% (19
      30%). DISCUSSION: In both communities a higher TB prevalence than national
      estimates and a low patient diagnostic rate was calculated, suggesting that cases
      are not detected at a sufficient rate to interrupt transmission. These findings
      may contribute to the rising TB incidence in South Africa. The TB epidemic should
      therefore be addressed rapidly and effectively, especially in the presence of the
      concurrently high HIV prevalence.

PMID- 23560040
TI  - Insulin-receptor substrate-2 (irs-2) is required for maintaining glucokinase and
      glucokinase regulatory protein expression in mouse liver.
AB  - Insulin receptor substrate (IRS) proteins play important roles in hepatic
      nutrient homeostasis. Since glucokinase (GK) and glucokinase regulatory protein
      (GKRP) function as key glucose sensors, we have investigated the expression of GK
      and GKRP in liver of Irs-2 deficient mice and Irs2(-/-) mice where Irs2 was
      reintroduced specifically into pancreatic beta-cells [RIP-Irs-2/IRS-2(-/-)]. We
      observed that liver GK activity was significantly lower (p<0.0001) in IRS-2(-/-)
      mice. However, in RIP-Irs-2/IRS-2(-/-) mice, GK activity was similar to the
      values observed in wild-type animals. GK activity in hypothalamus was not altered
      in IRS-2(-/-) mice. GK and GKRP mRNA levels in liver of IRS-2(-/-) were
      significantly lower, whereas in RIP-Irs-2/IRS-2(-/-) mice, both GK and GKRP mRNAs
      levels were comparable to wild-type animals. At the protein level, the liver
      content of GK was reduced in IRS-2(-/-) mice as compared with controls, although
      GKRP levels were similar between these experimental models. Both GK and GKRP
      levels were lower in RIP-Irs-2/IRS-2(-/-) mice. These results suggest that IRS-2
      signalling is important for maintaining the activity of liver GK. Moreover, the
      differences between liver and brain GK may be explained by the fact that
      expression of hepatic, but not brain, GK is controlled by insulin. GK activity
      was restored by the beta-cell compensation in the RIP-Irs-2/IRS-2 mice.
      Interestingly, GK and GKRP protein expression remained low in RIP-Irs-2/IRS-2(-/
      ) mice, perhaps reflecting different mRNA half-lives or alterations in the
      process of translation and post-translational regulation.

PMID- 23560041
TI  - UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms in association with obesity
      susceptibility - a meta-analysis study.
AB  - AIMS/HYPOTHESIS: Variants of UCP2 and UCP3 genes have been reported to be
      associated with obesity, but the available data on the relationship are
      inconsistent. A meta-analysis was performed to determine whether there are any
      associations between the UCP2 -866G/A, Ala55Val, and UCP3 -55C/T polymorphisms
      and obesity susceptibility. METHODS: The PubMed, Embase, Web of Science and CNKI,
      CBMdisc databases were searched for all relevant case-control studies. The fixed
      or random effect pooled measure was determined on the bias of heterogeneity test
      among studies. Publication bias was examined by the modified Begg's and Egger's
      test. RESULTS: Twenty-two published articles with thirty-two outcomes were
      included in the meta-analysis: 12 studies with a total of 7,390 cases and 9,860
      controls were analyzed for UCP2 -866G/A polymorphism with obesity, 9 studies with
      1,483 cases and 2,067 controls for UCP2 Ala55Val and 8 studies with 2,180 cases
      and 2,514 controls for UCP3 -55C/T polymorphism. Using an additive model, the
      UCP2 -866G/A polymorphism showed no significant association with obesity risk in
      Asians (REM OR = 0.81, 95% CI: 0.65-1.01). In contrast, a statistically
      significant association was observed in subjects of European descent (FEM OR =
      1.06, 95% CI: 1.01-1.12). But neither the UCP2 Ala55Val nor the UCP3 -55C/T
      polymorphism showed any significant association with obesity risk in either
      subjects of Asian (REM OR = 0.84, 95% CI: 0.67-1.06 for Ala55Val; REM OR = 0.94,
      95% CI: 0.55-1.28 for -55C/T) or of European descent (REM OR = 1.04, 95% CI: 0.80
      1.36 for Ala55Val; FEM OR = 1.08, 95% CI: 0.97-1.20 for -55C/T). CONCLUSIONS AND
      INTERPRETATION: Our meta-analysis revealed that the UCP2 -866G/A polymorphism may
      be a risk factor for susceptibility to obesity in subjects of European descent,
      but not in individuals of Asian descent. And our results did not support the
      association between UCP2 Ala55Val, UCP3 -55C/T polymorphisms and obesity in the
      populations investigated. This conclusion warrants confirmation by further
      studies.

PMID- 23560042
TI  - Real-time placental perfusion on contrast-enhanced ultrasound and parametric
      imaging analysis in rats at different gestation time and different portions of
      placenta.
AB  - OBJECTIVES: To quantitatively analyze placental perfusion in a rat model at
      different gestation time and different portions of placenta by real-time contrast
      enhanced ultrasound (CEUS) and parametric imaging analysis. MATERIALS AND
      METHODS: Sixty pregnant rats at different gestation time (15 dys,17 days and 20
      days) were injected intravenously with microbubbles (5*10(5) microbubbles /ml,
      1.0 ml/kg), and cadence contrast pulse sequencing (transmission frequency of 7
      MHz, mechanical index 0.18) was performed. Dynamic enhancement changes in
      placenta at different gestation time and different portions of placenta were
      measured and enhancement parameters analyzed with software. Correlation between
      enhancement parameters and average area densities of placenta vascular
      compartment was compared. RESULTS: The pattern and real-time sequence of
      enhancement in uterus and placenta were clearly depicted by CEUS. The time-to
      peak enhancement was earlier in central portion than that in peripheral portion
      (12.30+/-6.33s vs 36.26+/-10.65 s, p = 0.005), and peak intensity of enhancement
      is much higher in central portion than that in peripheral portion (30.20+/-2.85
      dB vs 20.95+/-6.25 dB, p = 0.000). The peak intensity of enhancement at day 15
      (27.70+/-4.47 dB) was lower than that at day 17 (30.20+/-2.85 dB, p = 0.042) and
      at day 20 (31.85+/-4.41 dB, p = 0.015) of gestation. Significant correlation
      between average area densities of vascular compartment and the peak intensity of
      enhancement was identified in placenta at different gestation time (p<0.05). The
      average area densities of vascular compartment was higher in central portion than
      that in peripheral portion and has significant correlation with peak intensity of
      enhancement of the two potions (p<0.01). CONCLUSION: CEUS is feasible to depict
      real-time sequence and quantitative parameters of perfusion in different portion
      of placenta at different gestational time in a rat model.

PMID- 23560044
TI  - Quantifying high resolution transitional breaks in plant and mammal distributions
      at regional extent and their association with climate, topography and geology.
AB  - OBJECTIVES: We quantify spatial turnover in communities of 1939 plant and 59
      mammal species at 2.5 km resolution across a topographically heterogeneous region
      in south-eastern Australia to identify distributional breaks and low turnover
      zones where multiple species distributions overlap. Environmental turnover is
      measured to determine how climate, topography and geology influence biotic
      turnover differently across a variety of biogeographic breaks and overlaps. We
      identify the genera driving turnover and confirm the versatility of this approach
      across spatial scales and locations. METHODS: Directional moving window analyses,
      rotated through 360 degrees , were used to measure spatial turnover variation in
      different directions between gridded cells containing georeferenced plant and
      mammal occurrences and environmental variables. Generalised linear models were
      used to compare taxic turnover results with equivalent analyses for geology,
      regolith weathering, elevation, slope, solar radiation, annual precipitation and
      annual mean temperature, both uniformly across the entire study area and by
      stratifying it into zones of high and low turnover. Identified breaks and
      transitions were compared to a conservation bioregionalisation framework widely
      used in Australia. RESULTS/SIGNIFICANCE: Detailed delineations of plant and
      mammal turnover zones with gradational boundaries denoted subtle variation in
      species assemblages. Turnover patterns often diverged from bioregion boundaries,
      though plant turnover adhered most closely. A prominent break zone contained
      either comparable or greater numbers of unique genera than adjacent overlaps, but
      these were concentrated in a small subsection relatively under-protected by
      conservation reserves. The environmental correlates of biotic turnover varied for
      different turnover zones in different subsections of the study area. Topography
      and temperature showed much stronger relationships with plant turnover in a
      topographically complex overlap, relative to a lowland overlap where weathering
      was most predictive. This method can quantify transitional turnover patterns from
      small to broad extents, at different resolutions for any location, and
      complements broad-scale bioregionalisation schemes in conservation planning.

PMID- 23560043
TI  - Screening of multiple myeloma by polyclonal rabbit anti-human plasmacytoma cell
      immunoglobulin.
AB  - Antibody-based immunotherapy has been effectively used for tumor treatment.
      However, to date, only a few tumor-associated antigens (TAAs) or therapeutic
      targets have been identified. Identification of more immunogenic antigens is
      essential for improvements in multiple myeloma (MM) diagnosis and therapy. In
      this study, we synthesized a polyclonal antibody (PAb) by immunizing rabbits with
      whole human plasmacytoma ARH-77 cells and identified MM-associated antigens,
      including enlonase, adipophilin, and HSP90s, among others, via proteomic
      technologies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      showed that 200 ug/mL PAb inhibits the proliferation of ARH-77 cells by over 50%
      within 48 h. Flow cytometric assay indicated that PAb treatment significantly
      increases the number of apoptotic cells compared with other treatments (52.1% vs.
      NS, 7.3% or control rabbit IgG, 9.9%). In vivo, PAb delayed tumor growth and
      prolonged the lifespan of mice. Terminal deoxynucleotidyl transferase dUTP nick
      end labeling assay showed that PAb also induces statistically significant changes
      in apoptosis compared with other treatments (P<0.05). We therefore conclude that
      PAb could be used for the effective screening and identification of TAA. PAb may
      have certain anti-tumor functions in vitro and in vivo. As such, its combination
      with proteomic technologies could be a promising approach for sieving TAA for the
      diagnosis and therapy of MM.

PMID- 23560045
TI  - Statistical analysis of sleep spindle occurrences.
AB  - Spindles - a hallmark of stage II sleep - are a transient oscillatory phenomenon
      in the EEG believed to reflect thalamocortical activity contributing to
      unresponsiveness during sleep. Currently spindles are often classified into two
      classes: fast spindles, with a frequency of around 14 Hz, occurring in the centro
      parietal region; and slow spindles, with a frequency of around 12 Hz, prevalent
      in the frontal region. Here we aim to establish whether the spindle generation
      process also exhibits spatial heterogeneity. Electroencephalographic recordings
      from 20 subjects were automatically scanned to detect spindles and the time
      occurrences of spindles were used for statistical analysis. Gamma distribution
      parameters were fit to each inter-spindle interval distribution, and a modified
      Wald-Wolfowitz lag-1 correlation test was applied. Results indicate that not all
      spindles are generated by the same statistical process, but this dissociation is
      not spindle-type specific. Although this dissociation is not topographically
      specific, a single generator for all spindle types appears unlikely.

PMID- 23560046
TI  - Time's up. descriptive epidemiology of multi-morbidity and time spent on health
      related activity by older Australians: a time use survey.
AB  - Most Western health systems remain single illness orientated despite the growing
      prevalence of multi-morbidity. Identifying how much time people with multiple
      chronic conditions spend managing their health will help policy makers and health
      service providers make decisions about areas of patient need for support. This
      article presents findings from an Australian study concerning the time spent on
      health related activity by older adults (aged 50 years and over), most of whom
      had multiple chronic conditions. A recall questionnaire was developed, piloted,
      and adjusted. Sampling was undertaken through three bodies; the Lung Foundation
      Australia (COPD sub-sample), National Diabetes Services Scheme (Diabetes sub
      sample) and National Seniors Australia (Seniors sub-sample). Questionnaires were
      mailed out during 2011 to 10,600 older adults living in Australia. 2540 survey
      responses were received and analysed. Descriptive analyses were completed to
      obtain median values for the hours spent on each activity per month. The mean
      number of chronic conditions was 3.7 in the COPD sub-sample, 3.4 in the Diabetes
      sub-sample and 2.0 in the NSA sub-sample. The study identified a clear trend of
      increased time use associated with increased number of chronic conditions. Median
      monthly time use was 5-16 hours per month overall for our three sub-samples. For
      respondents in the top decile with five or more chronic conditions the median
      time use was equivalent to two to three hours per day, and if exercise is
      included in the calculations, respondents spent from between five and eight hours
      per day: an amount similar to full-time work. Multi-morbidity imposes
      considerable time burdens on patients. Ageing is associated with increasing rates
      of multi-morbidity. Many older adults are facing high demands on their time to
      manage their health in the face of decreasing energy and mobility. Their time use
      must be considered in health service delivery and health system reform.

PMID- 23560047
TI  - Pathologic bladder microenvironment attenuates smooth muscle differentiation of
      skin derived precursor cells: implications for tissue regeneration.
AB  - Smooth muscle cell containing organs (bladder, heart, blood vessels) are damaged
      by a variety of pathological conditions necessitating surgery or organ
      replacement. Currently, regeneration of contractile tissues is hampered by lack
      of functional smooth muscle cells. Multipotent skin derived progenitor cells
      (SKPs) can easily be isolated from adult skin and can be differentiated in vitro
      into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an
      inhibitory effect of a pathologic contractile organ microenvironment on smooth
      muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces
      microenvironmental changes leading to de-differentiation of fully differentiated
      bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex
      vivo stretched bladders or exposure of SKPs to diffusible factors released by
      stretched bladders (e.g. bFGF) suppresses expression of smooth muscle markers
      (alpha SMactin, calponin, myocardin, myosin heavy chain) as demonstrated by qPCR
      and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling,
      previously observed to prevent bladder strain induced de-differentiation of fully
      differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle
      cell differentiation of undifferentiated SKPs. These results suggest that
      intended precursor cell differentiation may be paradoxically suppressed by the
      disease context for which regeneration may be required. Organ-specific
      microenvironment contexts, particularly prevailing disease, may play a
      significant role in modulating or attenuating an intended stem cell phenotypic
      fate, possibly explaining the variable and inefficient differentiation of stem
      cell constructs in in vivo settings. These observations must be considered in
      drafting any regeneration strategies.

PMID- 23560048
TI  - Burst BMP triggered receptor kinase activity drives Smad1 mediated long-term
      target gene oscillation in C2C12 cells.
AB  - Bone Morphogenetic Proteins (BMPs) are important growth factors that regulate
      many cellular processes. During embryogenesis they act as morphogens and play a
      critical role during organ development. They influence cell fates via
      concentration-gradients in the embryos where cells transduce this extracellular
      information into gene expression profiles and cell fate decisions. How receiving
      cells decode and quantify BMP2/4 signals is hardly understood. There is little
      data on the quantitative relationships between signal input, transducing
      molecules, their states and location, and ultimately their ability to integrate
      graded systemic inputs and generate qualitative responses. Understanding this
      signaling network on a quantitative level should be considered a prerequisite for
      efficient pathway modulation, as the BMP pathway is a prime target for
      therapeutic invention. Hence, we quantified the spatial distribution of the main
      signal transducer of the BMP2/4 pathway in response to different types and levels
      of stimuli in c2c12 cells. We found that the subcellular localization of Smad1 is
      independent of ligand concentration. In contrast, Smad1 phosphorylation levels
      relate proportionally to BMP2 ligand concentrations and they are entirely located
      in the nucleus. Interestingly, we found that BMP2 stimulates target gene
      expression in non-linear, wave-like forms. Amplitudes showed a clear
      concentration-dependency, for sustained and transient stimulation. We found that
      even burst-stimulation triggers gene-expression wave-like modulations that are
      detectable for at least 30 h. Finally, we show here that target gene expression
      oscillations depend on receptor kinase activity, as the kinase drives further
      expression pulses without receptor reactivation and the target gene expression
      breaks off after inhibitor treatment in c2c12 cells.

PMID- 23560049
TI  - Pre-diagnostic leukocyte genomic DNA methylation and the risk of colorectal
      cancer in women.
AB  - BACKGROUND: Abnormal one-carbon metabolism may lead to general genomic (global)
      hypomethylation, which may predispose an individual to the development of
      colorectal neoplasia. METHODS: We evaluated the association between pre
      diagnostic leukocyte genomic DNA methylation level and the risk of colorectal
      cancer in a nested case-control study of 358 colorectal cancer cases and 661
      matched controls within the all-female cohort of the Nurses' Health Study (NHS).
      Among control subjects, we further examined major plasma components in the one
      carbon metabolism pathway in relation to genomic DNA methylation level. Liquid
      chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA
      methylation level. We calculated odds ratios (ORs) and 95% confidence intervals
      (95% CIs) using logistic regression. RESULTS: Overall genomic DNA methylation
      level was not associated with the risk of colorectal cancer (p for trend, 0.45).
      Compared with women in the lowest quintile of methylation, the multivariate OR of
      colorectal cancer risk was 1.32 (95% CI, 0.82-2.13) for those in the highest
      quintile. We did not find significant associations between major plasma
      components of one-carbon metabolism or risk factors for colorectal cancer and
      genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon
      metabolism-related plasma components nor well-known risk factors for colorectal
      cancer modified the association between genomic DNA methylation level and the
      risk of colorectal cancer (all p for interaction >0.05). CONCLUSIONS: We found no
      evidence that hypomethylation of leukocyte genomic DNA increases risk of
      colorectal cancer among women. Additional studies are needed to investigate the
      association between pre-diagnostic genomic DNA methylation level and colorectal
      cancer risk among diverse populations.

PMID- 23560050
TI  - Comparison of Enterococcus faecium and Enterococcus faecalis Strains isolated
      from water and clinical samples: antimicrobial susceptibility and genetic
      relationships.
AB  - Enterococci are part of the normal intestinal flora in a large number of mammals,
      and these microbes are currently used as indicators of fecal contamination in
      water and food for human consumption. These organisms are considered one of the
      primary causes of nosocomial and environmental infections due to their ability to
      survive in the environment and to their intrinsic resistance to antimicrobials.
      The aims of this study were to determine the biochemical patterns and
      antimicrobial susceptibilities of Enterococcus faecalis and E. faecium isolates
      from clinical samples and from water (groundwater, water from the Xochimilco
      wetland, and treated water from the Mexico City Metropolitan Area) and to
      determine the genetic relationships among these isolates. A total of 121
      enterococcus strains were studied; 31 and 90 strains were isolated from clinical
      samples and water (groundwater, water from the Xochimilco wetland, and water for
      agricultural irrigation), respectively. Identification to the species level was
      performed using a multiplex PCR assay, and antimicrobial profiles were obtained
      using a commercial kit. Twenty-eight strains were analyzed by pulsed-field gel
      electrophoresis (PFGE). E. faecium strains isolated from water showed an atypical
      biochemical pattern. The clinical isolates showed higher resistance to
      antibiotics than those from water. Both the enterococci isolated from humans, and
      those isolated from water showed high genetic diversity according to the PFGE
      analysis, although some strains seemed to be closely related. In conclusion,
      enterococci isolated from humans and water are genetically different. However,
      water represents a potential route of transmission to the community and a source
      of antimicrobial resistance genes that may be readily transmitted to other,
      different bacterial species.

PMID- 23560051
TI  - A novel splice-site mutation in angiotensin I-converting enzyme (ACE) gene,
      c.3691+1G>A (IVS25+1G>A), causes a dramatic increase in circulating ACE through
      deletion of the transmembrane anchor.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many
      biologically active peptides and plays a key role in blood pressure regulation
      and vascular remodeling. Elevated ACE levels are associated with different
      cardiovascular and respiratory diseases. METHODS AND RESULTS: Two Belgian
      families with a 8-16-fold increase in blood ACE level were incidentally
      identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A
      (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both
      pedigrees. Messenger RNA analysis revealed that the mutation led to the retention
      of intron 25 and Premature Termination Codon generation. Subjects harboring the
      mutation were mostly normotensive, had no left ventricular hypertrophy or
      cardiovascular disease. The levels of renin-angiotensin-aldosterone system
      components in the mutated cases and wild-type controls were similar, both at
      baseline and after 50 mg captopril. Compared with non-affected members,
      quantification of ACE surface expression and shedding using flow cytometry assay
      of dendritic cells derived from peripheral blood monocytes of affected members,
      demonstrated a 50% decrease and 3-fold increase, respectively. Together with a
      dramatic increase in circulating ACE levels, these findings argue in favor of
      deletion of transmembrane anchor, leading to direct secretion of ACE out of
      cells. CONCLUSIONS: We describe a novel mutation of the ACE gene associated with
      a major familial elevation of circulating ACE, without evidence of activation of
      the renin-angiotensin system, target organ damage or cardiovascular
      complications. These data are consistent with the hypothesis that membrane-bound
      ACE, rather than circulating ACE, is responsible for Angiotensin II generation
      and its cardiovascular consequences.

PMID- 23560053
TI  - Enhancing specific-antibody production to the ragB vaccine with GITRL that expand
      Tfh, IFN-gamma(+) T cells and attenuates Porphyromonas gingivalis infection in
      mice.
AB  - The outer membrane protein RagB is one of the major virulence factors of the
      periodontal pathogen Porphyromonas gingivalis (P. gingivalis). In order to induce
      protective immune response against P. gingivalis infection, an mGITRL gene-linked
      ragB DNA vaccine (pIRES-ragB-mGITRL ) was constructed. Six-week-old female BALB/c
      mice were immunized with pIRES-ragB-mGITRL through intramuscular injection and
      then challenged by subcutaneous injection in the abdomen with P. gingivalis. RagB
      specific antibody-forming cells were evaluated by an Enzyme-linked immunosorbent
      spot, and specific antibody was determined by enzyme-linked immunosorbent assay.
      In addition, the frequencies of Tfh and IFN-gamma(+) T cells in spleen were
      measured using flow cytometer, and the levels of IL-21 and IFN-gamma mRNA or
      proteins were detected by real time RT-PCR or ELISA. The data showed that the
      mGITRL-linked ragB DNA vaccine induced higher levels of RagB-specific IgG in
      serum and RagB-specific antibody-forming cells in spleen. The frequencies of Tfh
      and IFN-gamma(+) T cells were obviously expanded in mice immunized by pIRES-ragB
      mGITRL compared with other groups (pIRES or pIRES-ragB ). The levels of Tfh and
      IFN-gamma(+) T cells associated cytokines were also significantly increased in
      pIRES-ragB-mGITRL group. Therefore, the mice immunized with ragB plus mGITRL
      showed the stronger resistant to P. gingivalis infection and a significant
      reduction of the lesion size caused by P. gingivalis infection comparing with
      other groups. Taken together, our findings demonstrated that intramuscular
      injection of DNA vaccine ragB together with mGITRL induced protective immune
      response dramatically by increasing Tfh and IFN-gamma(+) T cells and antibody
      production to P. gingivalis.

PMID- 23560052
TI  - Neuroinflammation and neuronal loss precede Abeta plaque deposition in the hAPP
      J20 mouse model of Alzheimer's disease.
AB  - Recent human trials of treatments for Alzheimer's disease (AD) have been largely
      unsuccessful, raising the idea that treatment may need to be started earlier in
      the disease, well before cognitive symptoms appear. An early marker of AD
      pathology is therefore needed and it is debated as to whether amyloid-betaAbeta?
      plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse
      model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust
      stereological methods, we found there is no neuron loss in the hippocampal CA3
      region at any age. However loss of neurons from the hippocampal CA1 region begins
      as early as 12 weeks of age. The extent of neuron loss increases with age,
      correlating with the number of activated microglia. Gliosis was also present, but
      plateaued during aging. Increased hyperactivity and spatial memory deficits
      occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric
      Abeta were essentially the last pathological changes, with significant changes
      only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD
      mouse model is engineered to over-expresses Abeta. Our data raises the
      possibility that plaque load may not be the best marker for early AD and suggests
      that activated microglia could be a valuable marker to track disease progression.

PMID- 23560054
TI  - High environmental temperature increases glucose requirement in the developing
      chicken embryo.
AB  - Environmental conditions during the perinatal period influence metabolic and
      developmental processes in mammals and avian species, which could impact pre- and
      postnatal survival and development. The current study investigated the effect of
      eggshell temperature (EST) on glucose metabolism in broiler chicken embryos.
      Broiler eggs were incubated at a high (38.9 degrees C) or normal (37.8 degrees C)
      EST from day 10.5 of incubation onward and were injected with a bolus of [U
      (13)C]glucose in the chorio-allantoic fluid at day 17.5 of incubation. After [U
      (13)C]glucose administration, (13)C enrichment was determined in intermediate
      pools and end-products of glucose metabolism. Oxidation of labeled glucose
      occurred for approximately 3 days after injection. Glucose oxidation was higher
      in the high than in the normal EST treatment from day 17.6 until 17.8 of
      incubation. The overall recovery of (13)CO2 tended to be 4.7% higher in the high
      than in the normal EST treatment. An increase in EST (38.9 degrees C vs 37.8
      degrees C) increased (13)C enrichment in plasma lactate at day 17.8 of incubation
      and (13)C in hepatic glycogen at day 18.8 of incubation. Furthermore, high
      compared to normal EST resulted in a lower yolk-free body mass at day 20.9 (-2.74
      g) and 21.7 (-3.81 g) of incubation, a lower hepatic glycogen concentration at
      day 18.2 (-4.37 mg/g) and 18.8 (-4.59 mg/g) of incubation, and a higher plasma
      uric acid concentration (+2.8 mg/mL/+43%) at day 21.6 of incubation. These
      results indicate that the glucose oxidation pattern is relatively slow, but the
      intensity increased consistently with an increase in developmental stage of the
      embryo. High environmental temperatures in the perinatal period of chicken
      embryos increased glucose oxidation and decreased hepatic glycogen prior to the
      hatching process. This may limit glucose availability for successful hatching and
      could impact body development, probably by increased gluconeogenesis from
      glucogenic amino acids to allow anaerobic glycolysis.

PMID- 23560055
TI  - Foxp3 (-/ATT) polymorphism contributes to the susceptibility of preeclampsia.
AB  - OBJECTIVE: To evaluate the potential influence of Foxp3 polymorphism on
      preeclampsia (PE) susceptibility, we conducted a case-control study in Han
      Chinese women. METHODS: Foxp3 genotyping was determined by polymerase chain
      reaction with sequence-specific primers (PCR-SSP) in 156 PE patients and 252 age
      frequency matched controls. Immunohistochemical staining was used to detect the
      expression of Foxp3 specific transcription factor in 30 PE and 30 normal pregnant
      women. RESULTS: The positive rate of Foxp3 expression in PE (26.67%) was
      significant difference from that in normal control (63.33%, P<0.05). The
      frequency of Foxp3-6054 TT genotype was significantly lower in PE patient than
      that in control. No significant difference was found in Foxp3-3279 genotypes
      between PE and control, as well as for the variant allele. The frequency of Foxp3
      6054A/-3279C haplotype in PE was significantly higher than that in control
      (P<0.01), while the frequency of Foxp3 6054T/-3279C haplotype was significantly
      lower in PE patient than that in control (P<0.01). CONCLUSION: Our findings
      suggest that the immune suppression function in PE patients is weakened, which
      may result in the occurrence of PE. Foxp3 polymorphism (rs5902434) may be a
      potential contributor for the development of PE in Han Chinese women.

PMID- 23560057
TI  - Higher fetal insulin resistance in Chinese pregnant women with gestational
      diabetes mellitus and correlation with maternal insulin resistance.
AB  - OBJECTIVE: The aim of this study was to determine the effect of gestational
      diabetes mellitus (GDM) on fetal insulin resistance or beta-cell function in
      Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous
      cord blood samples (reflecting fetal condition) were collected in 65 well
      controlled Chinese GDM mothers (only given dietary intervention) and 83 control
      subjects. The insulin, glucose and proinsulin concentrations of both maternal and
      cord blood samples were measured, and the homeostasis model assessment of insulin
      resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal
      beta-cell function) were calculated in maternal and cord blood respectively.
      RESULTS: Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but
      not proinsulin-to-insulin ratios were significantly higher in the GDM group than
      in the control group (maternal insulin, 24.8 vs. 15.4 uU/mL, P = 0.004,
      proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041,
      respectively; fetal: insulin, 15.1 vs. 7.9 uU/mL, P<0.001, proinsulin, 25.8 vs.
      15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal
      HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to
      maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM.
      CONCLUSIONS: Fetal insulin resistance was higher in Chinese pregnant women with
      GDM than control subjects, and correlated with maternal insulin resistance.

PMID- 23560056
TI  - Nesfatin-1/NUCB2 as a potential new element of sleep regulation in rats.
AB  - STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany
      severe illnesses such as major depression; a leading psychiatric disorder
      characterized by appetite and rapid eye movement sleep (REMS) abnormalities.
      Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly
      co - expressed in the hypothalamus and are involved both in food intake
      regulation and depression. Since MCH was recognized earlier as a hypnogenic
      factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We
      subjected rats to a 72 h-long REMS deprivation using the classic flower pot
      method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein
      expressions as well as neuronal activity (Fos) were measured by quantitative in
      situ hybridization technique, ELISA and immunohistochemistry, respectively, in
      'deprived' and 'rebound' groups, relative to controls sacrificed at the same
      time. We also analyzed electroencephalogram of rats treated by
      intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS
      deprivation downregulated the expression of nesfatin (mRNA and protein), however,
      enhanced REMS during 'rebound' reversed this to control levels. Additionally,
      increased transcriptional activity (Fos) was demonstrated in nesfatin neurons
      during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and
      intermediate stage of sleep, while increased passive wake for several hours and
      also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data
      designate nesfatin as a potential new factor in sleep regulation, which fact can
      also be relevant in the better understanding of the role of nesfatin in the
      pathomechanism of depression.

PMID- 23560059
TI  - Regional cardiac dysfunction and dyssynchrony in a murine model of afterload
      stress.
AB  - Small animal models of afterload stress have contributed much to our present
      understanding of the progression from hypertension to heart failure. High
      sensitivity methods for phenotyping cardiac function in vivo, particular in the
      setting of compensated cardiac hypertrophy, may add new information regarding
      alterations in cardiac performance that can occur even during the earliest stages
      of exposure to pressure overload. We have developed an echocardiographic
      analytical method, based on speckle-tracking-based strain analyses, and used this
      tool to rapidly phenotype cardiac changes resulting from afterload stress in a
      small animal model. Adult mice were subjected to ascending aortic constriction,
      with and without subsequent reversal of the pressure gradient. In this model of
      compensated hypertrophic cardiac remodeling, conventional echocardiographic
      measurements did not detect changes in left ventricular (LV) function at the
      early time points examined. Strain analyses, however, revealed a decrement in
      basal longitudinal myofiber shortening that was induced by aortic constriction
      and improved following relief of the pressure gradient. Furthermore, we observed
      that pressure overload resulted in LV segmental dyssynchrony that was attenuated
      with return of the afterload to baseline levels. Herein, we describe the use of
      echocardiographic strain analyses for cardiac phenotyping in a mouse model of
      pressure overload. This method provides evidence of dyssynchrony and regional
      myocardial dysfunction that occurs early with compensatory hypertrophy, and
      improves following relief of aortic constriction. Importantly, these findings
      illustrate the utility of a rapid, non-invasive method for characterizing early
      cardiac dysfunction, not detectable by conventional echocardiography, following
      afterload stress.

PMID- 23560058
TI  - Two 4N cell-cycle arrests contribute to cisplatin-resistance.
AB  - Cisplatin is a platinum-based drug that is used for the treatment of a wide
      variety of primary human cancers. However, the therapeutic efficacy of cisplatin
      is often limited by intrinsic or acquired drug resistance. An important goal,
      therefore, is to identify mechanisms that lead to cisplatin resistance in cancer,
      and then use this information to more effectively target resistant cells.
      Cisplatin-resistant clones of the HCT116 cell line underwent a prolonged G2
      arrest after cisplatin treatment while sensitive clones did not. The
      staurosporine analog UCN-01 abrogated this G2 arrest and sensitized the resistant
      clones to cisplatin. At later time points, 4N arrested cells assumed a tetraploid
      G1 state that was characterized by depletion of Cyclin A, Cyclin B, and CDC2, and
      increased expression of p53 and p21, in 4N cells. siRNA-mediated knockdown of p21
      abrogated the tetraploid G1 arrest and induced killing that was dependent on p53.
      The results identify two targetable 4N arrests that can contribute to cisplatin
      resistance: First, a prolonged G2 arrest that can be targeted by UCN-01, and
      second, a tetraploid G1 arrest that can be targeted by siRNA against p21.

PMID- 23560060
TI  - Airflow dynamics of human jets: sneezing and breathing - potential sources of
      infectious aerosols.
AB  - Natural human exhalation flows such as coughing, sneezing and breathing can be
      considered as 'jet-like' airflows in the sense that they are produced from a
      single source in a single exhalation effort, with a relatively symmetrical,
      conical geometry. Although coughing and sneezing have garnered much attention as
      potential, explosive sources of infectious aerosols, these are relatively rare
      events during daily life, whereas breathing is necessary for life and is
      performed continuously. Real-time shadowgraph imaging was used to visualise and
      capture high-speed images of healthy volunteers sneezing and breathing (through
      the nose - nasally, and through the mouth - orally). Six volunteers, who were
      able to respond to the pepper sneeze stimulus, were recruited for the sneezing
      experiments (2 women: 27.5+/-6.36 years; 4 men: 29.25+/-10.53 years). The maximum
      visible distance over which the sneeze plumes (or puffs) travelled was 0.6 m, the
      maximum sneeze velocity derived from these measured distances was 4.5 m/s. The
      maximum 2-dimensional (2-D) area of dissemination of these sneezes was 0.2 m(2).
      The corresponding derived parameter, the maximum 2-D area expansion rate of these
      sneezes was 2 m(2)/s. For nasal breathing, the maximum propagation distance and
      derived velocity were 0.6 m and 1.4 m/s, respectively. The maximum 2-D area of
      dissemination and derived expansion rate were 0.11 m(2) and 0.16 m(2)/s,
      respectively. Similarly, for mouth breathing, the maximum propagation distance
      and derived velocity were 0.8 m and 1.3 m/s, respectively. The maximum 2-D area
      of dissemination and derived expansion rate were 0.18 m(2) and 0.17 m(2)/s,
      respectively. Surprisingly, a comparison of the maximum exit velocities of
      sneezing reported here with those obtained from coughing (published previously)
      demonstrated that they are relatively similar, and not extremely high. This is in
      contrast with some earlier estimates of sneeze velocities, and some reasons for
      this difference are discussed.

PMID- 23560062
TI  - Vehicle exhaust gas clearance by low temperature plasma-driven nano-titanium
      dioxide film prepared by radiofrequency magnetron sputtering.
AB  - A novel plasma-driven catalysis (PDC) reactor with special structure was proposed
      to remove vehicle exhaust gas. The PDC reactor which consisted of three quartz
      tubes and two copper electrodes was a coaxial dielectric barrier discharge (DBD)
      reactor. The inner and outer electrodes firmly surrounded the outer surface of
      the corresponding dielectric barrier layer in a spiral way, respectively. Nano
      titanium dioxide (TiO2) film prepared by radiofrequency (RF) magnetron sputtering
      was coated on the outer wall of the middle quartz tube, separating the catalyst
      from the high voltage electrode. The spiral electrodes were designed to avoid
      overheating of microdischarges inside the PDC reactor. Continuous operation tests
      indicated that stable performance without deterioration of catalytic activity
      could last for more than 25 h. To verify the effectiveness of the PDC reactor, a
      non-thermal plasma(NTP) reactor was employed, which has the same structure as the
      PDC reactor but without the catalyst. The real vehicle exhaust gas was introduced
      into the PDC reactor and NTP reactor, respectively. After the treatment, compared
      with the result from NTP, the concentration of HC in the vehicle exhaust gas
      treated by PDC reactor reduced far more obviously while that of NO decreased only
      a little. Moreover, this result was explained through optical emission spectrum.
      The O emission lines can be observed between 870 nm and 960 nm for wavelength in
      PDC reactor. Together with previous studies, it could be hypothesized that O
      derived from catalytically O3 destruction by catalyst might make a significant
      contribution to the much higher HC removal efficiency by PDC reactor. A series of
      complex chemical reactions caused by the multi-components mixture in real vehicle
      exhaust reduced NO removal efficiency. A controllable system with a real-time
      feedback module for the PDC reactor was proposed to further improve the ability
      of removing real vehicle exhaust gas.

PMID- 23560061
TI  - Remodeling of oxidative energy metabolism by galactose improves glucose handling
      and metabolic switching in human skeletal muscle cells.
AB  - Cultured human myotubes have a low mitochondrial oxidative potential. This study
      aims to remodel energy metabolism in myotubes by replacing glucose with galactose
      during growth and differentiation to ultimately examine the consequences for
      fatty acid and glucose metabolism. Exposure to galactose showed an increased
      [(14)C]oleic acid oxidation, whereas cellular uptake of oleic acid uptake was
      unchanged. On the other hand, both cellular uptake and oxidation of
      [(14)C]glucose increased in myotubes exposed to galactose. In the presence of the
      mitochondrial uncoupler carbonylcyanide p-trifluormethoxy-phenylhydrazone (FCCP)
      the reserve capacity for glucose oxidation was increased in cells grown with
      galactose. Staining and live imaging of the cells showed that myotubes exposed to
      galactose had a significant increase in mitochondrial and neutral lipid content.
      Suppressibility of fatty acid oxidation by acute addition of glucose was
      increased compared to cells grown in presence of glucose. In summary, we show
      that cells grown in galactose were more oxidative, had increased oxidative
      capacity and higher mitochondrial content, and showed an increased glucose
      handling. Interestingly, cells exposed to galactose showed an increased
      suppressibility of fatty acid metabolism. Thus, galactose improved glucose
      metabolism and metabolic switching of myotubes, representing a cell model that
      may be valuable for metabolic studies related to insulin resistance and disorders
      involving mitochondrial impairments.

PMID- 23560063
TI  - The structure of microbial community and degradation of diatoms in the deep near
      bottom layer of Lake Baikal.
AB  - Insight into the role of bacteria in degradation of diatoms is important for
      understanding the factors and components of silica turnover in aquatic
      ecosystems. Using microscopic methods, it has been shown that the degree of
      diatom preservation and the numbers of diatom-associated bacteria in the surface
      layer of bottom sediments decrease with depth; in the near-bottom water layer,
      the majority of bacteria are associated with diatom cells, being located either
      on the cell surface or within the cell. The structure of microbial community in
      the near-bottom water layer has been characterized by pyrosequencing of the 16S
      rRNA gene, which has revealed 149 208 unique sequences. According to the results
      of metagenomic analysis, the community is dominated by representatives of
      Proteobacteria (41.9%), Actinobacteria (16%); then follow Acidobacteria (6.9%),
      Cyanobacteria (5%), Bacteroidetes (4.7%), Firmicutes (2.8%), Nitrospira (1.6%),
      and Verrucomicrobia (1%); other phylotypes account for less than 1% each. For
      18.7% of the sequences, taxonomic identification has been possible only to the
      Bacteria domain level. Many bacteria identified to the genus level have close
      relatives occurring in other aquatic ecosystems and soils. The metagenome of the
      bacterial community from the near-bottom water layer also contains 16S rRNA gene
      sequences found in previously isolated bacterial strains possessing hydrolytic
      enzyme activity. These data show that potential degraders of diatoms occur among
      the vast variety of microorganisms in the near-bottom water of Lake Baikal.

PMID- 23560064
TI  - Ginseng for health care: a systematic review of randomized controlled trials in
      Korean literature.
AB  - OBJECTIVE: This systematic review was performed to summarise randomised clinical
      trials (RCTs) assessing the efficacy and safety of ginseng in the Korean
      literature. METHOD: The study involved systematic searches conducted in eight
      Korean Medical databases. The methodological quality of all of the included
      studies was assessed using the Cochrane Risk of Bias tool. We included all RCTs
      on any type of ginseng compared to placebo, active treatment or no treatment in
      healthy individuals or patients regardless of conditions. RESULTS: In total, 1415
      potentially relevant studies were identified, and 30 randomised clinical trials
      were included. Nine RCTs assessed the effects of ginseng on exercise capacity,
      cognitive performance, somatic symptoms, quality of life, and sleeping in healthy
      persons. Six RCTs tested ginseng compared with placebo for erectile dysfunction,
      while another four studies evaluated the effects of ginseng against no treatment
      for gastric and colon cancer. Two RCTs compared the effect of red ginseng on
      diabetes mellitus with no treatment or placebo, and the other nine RCTs assessed
      the effects of ginseng compared with placebo or no treatment on various
      conditions. The methodological caveats of the included trials make their
      contribution to the current clinical evidence of ginseng somewhat limited.
      However, the 20 newly added trials (66.7% of the 30 trials) may provide useful
      information for future trials. Ginseng appears to be generally safe, and no
      serious adverse effects have been reported. CONCLUSIONS: The clinical effects of
      ginseng have been tested in a wide range of conditions in Korea. Although the
      quality of RCTs published in the Korean literature was generally poor, this
      review is useful for researchers to access studies that were originally published
      in languages that they would otherwise be unable to read and due to the paucity
      of evidence on this subject.

PMID- 23560065
TI  - Coalescent-based genome analyses resolve the early branches of the
      euarchontoglires.
AB  - Despite numerous large-scale phylogenomic studies, certain parts of the mammalian
      tree are extraordinarily difficult to resolve. We used the coding regions from 19
      completely sequenced genomes to study the relationships within the super-clade
      Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia)
      because the placement of Scandentia within this clade is controversial. The
      difficulty in resolving this issue is due to the short time spans between the
      early divergences of Euarchontoglires, which may cause incongruent gene trees.
      The conflict in the data can be depicted by network analyses and the contentious
      relationships are best reconstructed by coalescent-based analyses. This method is
      expected to be superior to analyses of concatenated data in reconstructing a
      species tree from numerous gene trees. The total concatenated dataset used to
      study the relationships in this group comprises 5,875 protein-coding genes
      (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs).
      Reconstruction of the species tree from 1,006 gene trees using coalescent models
      placed Scandentia as sister group to the primates, which is in agreement with
      maximum likelihood analyses of concatenated nucleotide sequence data.
      Additionally, both analytical approaches favoured the Tarsier to be sister taxon
      to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times
      are short such as in radiations over periods of a few million years, even genome
      scale analyses struggle to resolve phylogenetic relationships. On these short
      branches processes such as incomplete lineage sorting and possibly hybridization
      occur and make it preferable to base phylogenomic analyses on coalescent methods.

PMID- 23560066
TI  - Specific gene bciD for C7-methyl oxidation in bacteriochlorophyll e biosynthesis
      of brown-colored green sulfur bacteria.
AB  - The gene named bciD, which encodes the enzyme involved in C7-formylation in
      bacteriochlorophyll e biosynthesis, was found and investigated by insertional
      inactivation in the brown-colored green sulfur bacterium Chlorobaculum limnaeum
      (previously called Chlorobium phaeobacteroides). The bciD mutant cells were green
      in color, and accumulated bacteriochlorophyll c homologs bearing the 7-methyl
      group, compared to C7-formylated BChl e homologs in the wild type. BChl-c homolog
      compositions in the mutant were further different from those in Chlorobaculum
      tepidum which originally produced BChl c: (3(1) S)-8-isobutyl-12-ethyl-BChl c was
      unusually predominant.

PMID- 23560067
TI  - Investigation of tumor suppressing function of CACNA2D3 in esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Deletion of 3p is one of the most frequent genetic alterations in
      esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or
      more tumor suppressor genes (TSGs) within these regions. In this study, one TSG,
      CACNA2D3 at 3p21.1, was characterized. METHODS: Expression of CACNA2D3 in ESCCs
      was tested by quantitative real-time PCR and tissue microarray. The mechanism of
      CACNA2D3 downregulation was investigated by methylation-specific polymerase chain
      reaction (MS-PCR). The tumor suppressive function of CACNA2D3 was characterized
      by both in vitro and in vivo tumorigenic assays, cell migration and invasion
      assays. RESULTS: CACNA2D3 was frequently downregulated in ESCCs (24/48, 50%),
      which was significantly associated with promoter methylation and allele loss
      (P<0.05). Tissue microarray result showed that downregulation of CACNA2D3 was
      detected in (127/224, 56.7%) ESCCs, which was significantly associated with lymph
      node metastasis (P = 0.01), TNM staging (P = 0.003) and poor outcome of ESCC
      patients (P<0.05). Functional studies demonstrated that CACNA2D3 could inhibit
      tumorigenicity, cell motility and induce apoptosis. Mechanism study found that
      CACNA2D3 could arrest cell cycle at G1/S checkpoint by increasing expressions of
      p21 and p53 and decreasing expression of CDK2. In addition, CACNA2D3 could
      upregulate intracellular free cytosolic Ca(2+) and subsequently induce apoptosis.
      CONCLUSION: CACNA2D3 is a novel TSG responsible to the 3p21 deletion event and
      plays a critical suppressing role in the development and progression of ESCC.

PMID- 23560069
TI  - Health survey of numbness/pain and its associated factors in Kotohira, Japan.
AB  - We conducted a survey of adults in Kotohira, a town of about 10,000 people
      located in the Nakatado District of Kagawa Prefecture, Japan. The survey was
      distributed to 8184 individuals, and effective responses were received from 3863
      persons (response rate, 47.2%) during the survey period. Results regarding
      numbness and pain showed numbness alone in 7.7%, pain alone in 7.2%, both
      numbness and pain in 6.0%, and neither numbness nor pain in 79.6%. Spine and
      spinal cord damage was reported present by 5.4%, and absent by 94.6%. Analysis
      using the Short-Form Health Survey questionnaire, with comparison between
      subjects reporting both numbness and pain in the extremities and subjects with
      either numbness or pain alone, showed lower scores for in Short-Form Health
      Survey subscales (physical functioning, role [physical, emotional], bodily pain,
      vitality, and mental health). Subjects with numbness alone generally reported no
      disability in daily life. In a secondary survey, analysis of neurological
      findings by specialists identified 6 cases of "pain following spinal cord damage"
      in which spinal cord-related pain developed in the hands or feet. This
      represented 0.15% of the survey population starting from the primary survey.

PMID- 23560068
TI  - Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+)
      melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy.
AB  - Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can
      induce tumor regression in up to 50% or more of patients with unresectable
      metastatic melanoma. However, current methods to expand melanoma TIL, especially
      the "rapid expansion protocol" (REP) were not designed to enhance the generation
      of optimal effector-memory CD8(+) T cells for infusion. One approach to this
      problem is to manipulate specific co-stimulatory signaling pathways to enhance
      CD8(+) effector-memory T-cell expansion. In this study, we determined the effects
      of activating the TNF-R family member 4-1BB/CD137, specifically induced in
      activated CD8(+) T cells, on the yield, phenotype, and functional activity of
      expanded CD8(+) T cells during the REP. We found that CD8(+) TIL up-regulate 4
      1BB expression early during the REP after initial TCR stimulation, but neither
      the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand.
      However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513) to the
      REP significantly enhanced the frequency and total yield of CD8(+) T cells as
      well as their maintenance of CD28 and increased their anti-tumor CTL activity.
      Gene expression analysis found an increase in bcl-2 and survivin expression
      induced by 4-1BB that was associated with an enhanced survival capability of
      CD8(+) post-REP TIL when re-cultured in the absence or presence of cytokines. Our
      findings suggest that adding an agonistic anti-4-1BB antibody during the time of
      TIL REP initiation produces a CD8(+) T cell population capable of improved
      effector function and survival. This may greatly improve TIL persistence and anti
      tumor activity in vivo after adoptive transfer into patients.

PMID- 23560070
TI  - Tertiary origin and pleistocene diversification of dragon blood tree (Dracaena
      cambodiana-Asparagaceae) populations in the Asian tropical forests.
AB  - BACKGROUND: The origin of extraordinarily rich biodiversity in tropical forests
      is often attributed to evolution under stable climatic conditions over a long
      period or to climatic fluctuations during the recent Quaternary period. Here, we
      test these two hypotheses using Dracaena cambodiana, a plant species distributed
      in paleotropical forests. METHODS: WE ANALYZED NUCLEOTIDE SEQUENCE DATA OF TWO
      CHLOROPLAST DNA (CPDNA: atpB-rbcL and trnD-trnT) regions and genotype data of six
      nuclear microsatellites from 15 populations (140 and 363 individuals,
      respectively) distributed in Indochina Peninsular and Hainan Island to infer the
      patterns of genetic diversity and phylogeographic structure. The population
      bottleneck and genetic drift were estimated based upon nuclear microsatellites
      data using the software programs BOTTLENECK and 2MOD. The lineage divergence
      times and past population dynamics based on cpDNA data were estimated using
      coalescent-based isolation-with-migration (IMa) and BEAST software programs.
      RESULTS: A significant phylogeographic structure (N ST = 0.876, G ST = 0.796, F
      ST-SSR = 0.329, R ST = 0.449; N ST>G ST, R ST>F ST-SSR, P<0.05) and genetic
      differentiation among populations were detected. Bottleneck analyses and Bayesian
      skyline plot suggested recent population reduction. The cpDNA haplotype network
      revealed the ancestral populations from the southern Indochina region expanded to
      northward. The most recent ancestor divergence time of D. cambodiana dated back
      to the Tertiary era and rapid diversification of terminal lineages corresponded
      to the Quaternary period. CONCLUSIONS: The results indicated that the present
      distribution of genetic diversity in D. cambodiana was an outcome of Tertiary
      dispersal and rapid divergence during the Quaternary period under limited gene
      flow influenced by the uplift of Himalayan-Tibetan Plateau and Quaternary
      climatic fluctuations respectively. Evolutionary processes, such as extinction
      recolonization during the Pleistocene may have contributed to the fast
      diversification in D. cambodiana.

PMID- 23560071
TI  - Community based promotion on VCT acceptance among rural migrants in Shanghai,
      China.
AB  - OBJECTIVE: Voluntary counseling and testing (VCT) plays an important integral
      role in response to the HIV/AIDS epidemic. However, VCT service has not been
      effectively utilized among rural migrants, a high risk group in China. In this
      study, we developed a community based intervention to examine if community
      mobilization with comprehensive VCT is more effective than current HIV
      preventions with routine VCT service in promoting VCT acceptability among rural
      migrants in Shanghai, China. METHODS: A comprehensive intervention with community
      mobilization and comprehensive VCT services including community-based VCT and
      mobile VCT was implemented during 2007-2009. Three communities in Minhang
      District of Shanghai were randomly selected and were designed to receive
      community mobilization and comprehensive VCT, traditional VCT and none
      intervention, respectively. After 24 months intervention, effects were evaluated
      by comparing outcome indicators between the baseline (2,690 participants) and
      follow-up surveys (1,850 participants). FINDINGS: A substantial increase in VCT
      acceptance was observed among community mobilization group (94.9% vs. 88.5%,
      P<0.001), whereas the reverse effect was seen in the traditional VCT group (86.1%
      vs. 94.6%, P<0.001) and control group (69.0% vs. 91.7%, P<0.001). Rural migrants
      from community mobilization group were more likely to accept VCT (OR = 2.91, 95%
      CI 1.69-4.97). Rural migrants from community mobilization group also showed
      significant increase in HIV/AIDS knowledge, positive attitude towards HIV
      positive individuals and condom use. CONCLUSION: Community mobilization with
      comprehensive VCT has significant impact on promotion of VCT acceptance and
      utilization among rural migrants in Shanghai. These findings provide evidence to
      support community mobilization as a suitable strategy for VCT promotion among
      rural migrants in Shanghai, China.

PMID- 23560072
TI  - Genotyping Cryptosporidium andersoni in cattle in Shaanxi Province, Northwestern
      China.
AB  - The present study examined the prevalence and genotypes of Cryptosporidium
      andersoni in cattle in Shaanxi province, China. A total of 2071 fecal samples
      (847 from Qinchuan cattle and 1224 from dairy cattle) were examined for the
      presence of Cryptosporidium oocysts, and 70 samples (3.4%) were C. andersoni
      positive and those positive samples were identified by PCR amplification of the
      small subunit ribosomal RNA (SSU rRNA) and the Cryptosporidium oocyst wall
      protein (COWP) genes. C. andersoni was the only species found in the examined
      cattle in this province. Fifty-seven C. andersoni isolates were characterized
      into 5 MLST subtypes using multilocus sequence typing analysis, including a new
      subtype in the native beef breed Qinchuan cattle. All of these C. andersoni
      isolates presented a clonal genetic structure. These findings provide new
      insights into the genetic structure of C. andersoni isolates in Shaanxi province
      and basic data of Cryptosporidium prevalence status, which in turn have
      implications for controlling cryptosporidiosis in this province.

PMID- 23560073
TI  - What does brain response to neutral faces tell us about major depression?
      evidence from machine learning and fMRI.
AB  - INTRODUCTION: A considerable number of previous studies have shown abnormalities
      in the processing of emotional faces in major depression. Fewer studies, however,
      have focused specifically on abnormal processing of neutral faces despite
      evidence that depressed patients are slow and less accurate at recognizing
      neutral expressions in comparison with healthy controls. The current study aimed
      to investigate whether this misclassification described behaviourally for neutral
      faces also occurred when classifying patterns of brain activation to neutral
      faces for these patients. METHODS: TWO INDEPENDENT DEPRESSED SAMPLES: (1)
      Nineteen medication-free patients with depression and 19 healthy volunteers and
      (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy
      volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI
      experiment. We used a new pattern recognition framework: first, we trained the
      classifier to discriminate between two brain states (e.g. viewing happy faces vs.
      viewing neutral faces) using data only from healthy controls (HC). Second, we
      tested the classifier using patterns of brain activation of a patient and a
      healthy control for the same stimuli. Finally, we tested if the classifier's
      predictions (predictive probabilities) for emotional and neutral face
      classification were different for healthy controls and depressed patients.
      RESULTS: Predictive probabilities to patterns of brain activation to neutral
      faces in both groups of patients were significantly lower in comparison to the
      healthy controls. This difference was specific to neutral faces. There were no
      significant differences in predictive probabilities to patterns of brain
      activation to sad faces (sample 1) and happy faces (samples 2) between depressed
      patients and healthy controls. CONCLUSIONS: Our results suggest that the pattern
      of brain activation to neutral faces in depressed patients is not consistent with
      the pattern observed in healthy controls subject to the same stimuli. This
      difference in brain activation might underlie the behavioural misinterpretation
      of the neutral faces content by the depressed patients.

PMID- 23560074
TI  - Bone marrow progenitor cell therapy-mediated paracrine regulation of cardiac
      miRNA-155 modulates fibrotic response in diabetic hearts.
AB  - Diabetes is associated with a higher incidence of myocardial infarction (MI) and
      increased risk for adverse vascular and fibrogenic events post-MI. Bone marrow
      derived progenitor cell (BMPC) therapy has been shown to promote
      neovascularization, decrease infarct area and attenuate left ventricular (LV)
      dysfunction after MI. Unlike vascular effects, the anti-fibrosis mechanisms of
      BMPC, specifically under diabetic conditions, are poorly understood. We
      demonstrated that intramyocardial delivery of BMPCs in infarcted diabetic db/db
      mice significantly down-regulates profibrotic miRNA-155 in the myocardium and
      improves LV remodeling and function. Furthermore, inhibition of paracrine factor
      hepatocyte growth factor (HGF) signaling in vivo suppressed the BMPC-mediated
      inhibition of miR-155 expression and the associated protective effect on cardiac
      fibrosis and function. In vitro studies confirmed that the conditioned media of
      BMPC inhibited miR-155 expression and profibrotic signaling in mouse cardiac
      fibroblasts under diabetic conditions. However, neutralizing antibodies directed
      against HGF blocked these effects. Furthermore, miR-155 over-expression in mouse
      cardiac fibroblasts inhibited antifibrotic Sloan-Kettering Institute proto
      oncogene (Ski) and Ski-related novel gene, non-Alu-containing (SnoN) signaling
      and abrogated antifibrogenic response of HGF. Together, our data demonstrates
      that paracrine regulation of cardiac miRNAs by transplanted BMPCs contributes to
      the antifibrotic effects of BMPC therapy. BMPCs release HGF, which inhibits miR
      155-mediated profibrosis signaling, thereby preventing cardiac fibrosis. These
      data suggest that targeting miR-155 might serve as a potential therapy against
      cardiac fibrosis in the diabetic heart.

PMID- 23560076
TI  - U-shape suppressive effect of phenol red on the epileptiform burst activity via
      activation of estrogen receptors in primary hippocampal culture.
AB  - Phenol red is widely used in cell culture as a pH indicator. Recently, it also
      has been reported to have estrogen-like bioactivity and be capable of promoting
      cell proliferation in different cell lines. However, the effect of phenol red on
      primary neuronal culture has never been investigated. By using patch clamp
      technique, we demonstrated that hippocampal pyramidal neurons cultured in
      neurobasal medium containing no phenol red had large depolarization-associated
      epileptiform bursting activities, which were rarely seen in neurons cultured in
      phenol red-containing medium. Further experiment data indicate that the
      suppressive effect of the phenol red on the abnormal epileptiform burst neuronal
      activities was U-shape dose related, with the most effective concentration at 28
      uM. In addition, this concentration related inhibitory effect of phenol red on
      the epileptiform neuronal discharges was mimicked by 17-beta-estradiol, an
      estrogen receptor agonist, and inhibited by ICI-182,780, an estrogen receptor
      antagonist. Our results suggest that estrogen receptor activation by phenol red
      in the culture medium prevents formation of abnormal, epileptiform burst
      activity. These studies highlight the importance of phenol red as estrogen
      receptor stimulator and cautions of careful use of phenol red in cell culture
      media.

PMID- 23560075
TI  - Transcriptome analysis of the differentially expressed genes in the male and
      female shrub willows (Salix suchowensis).
AB  - BACKGROUND: The dioecious system is relatively rare in plants. Shrub willow is an
      annual flowering dioecious woody plant, and possesses many characteristics that
      lend it as a great model for tracking the missing pieces of sex determination
      evolution. To gain a global view of the genes differentially expressed in the
      male and female shrub willows and to develop a database for further studies, we
      performed a large-scale transcriptome sequencing of flower buds which were
      separately collected from two types of sexes. RESULTS: Totally, 1,201,931 high
      quality reads were obtained, with an average length of 389 bp and a total length
      of 467.96 Mb. The ESTs were assembled into 29,048 contigs, and 132,709
      singletons. These unigenes were further functionally annotated by comparing their
      sequences to different proteins and functional domain databases and assigned with
      Gene Ontology (GO) terms. A biochemical pathway database containing 291 predicted
      pathways was also created based on the annotations of the unigenes. Digital
      expression analysis identified 806 differentially expressed genes between the
      male and female flower buds. And 33 of them located on the incipient sex
      chromosome of Salicaceae, among which, 12 genes might involve in plant sex
      determination empirically. These genes were worthy of special notification in
      future studies. CONCLUSIONS: In this study, a large number of EST sequences were
      generated from the flower buds of a male and a female shrub willow. We also
      reported the differentially expressed genes between the two sex-type flowers.
      This work provides valuable information and sequence resources for uncovering the
      sex determining genes and for future functional genomics analysis of Salicaceae
      spp.

PMID- 23560077
TI  - GSE is a maternal factor involved in active DNA demethylation in zygotes.
AB  - After fertilization, the sperm and oocyte genomes undergo extensive epigenetic
      reprogramming to form a totipotent zygote. The dynamic epigenetic changes during
      early embryo development primarily involve DNA methylation and demethylation. We
      have previously identified Gse (gonad-specific expression gene) to be expressed
      specifically in germ cells and early embryos. Its encoded protein GSE is
      predominantly localized in the nuclei of cells from the zygote to blastocyst
      stages, suggesting possible roles in the epigenetic changes occurring during
      early embryo development. Here, we report the involvement of GSE in epigenetic
      reprogramming of the paternal genome during mouse zygote development.
      Preferential binding of GSE to the paternal chromatin was observed from
      pronuclear stage 2 (PN2) onward. A knockdown of GSE by antisense RNA in oocytes
      produced no apparent effect on the first and second cell cycles in
      preimplantation embryos, but caused a significant reduction in the loss of 5
      methylcytosine (5mC) and the accumulation of 5-hydroxymethylcytosine (5hmC) in
      the paternal pronucleus. Furthermore, DNA methylation levels in CpG sites of
      LINE1 transposable elements, Lemd1, Nanog and the upstream regulatory region of
      the Oct4 (also known as Pou5f1) gene were clearly increased in GSE-knockdown
      zygotes at mid-pronuclear stages (PN3-4), but the imprinted H19-differential
      methylated region was not affected. Importantly, DNA immunoprecipitation of 5mC
      and 5hmC also indicates that knockdown of GSE in zygotes resulted in a
      significant reduction of the conversion of 5mC to 5hmC on LINE1. Therefore, our
      results suggest an important role of maternal GSE for mediating active DNA
      demethylation in the zygote.

PMID- 23560079
TI  - Phosphorylated C/EBPbeta influences a complex network involving YY1 and USF2 in
      lung epithelial cells.
AB  - The promoter of the cystic fibrosis transmembrane conductance regulator gene CFTR
      is tightly controlled by regulators including CCAAT/enhancer binding proteins
      (C/EBPs). We previously reported that the transcription factors YY1 and USF2
      affect CFTR expression. We can now demonstrate that C/EBPbeta, a member of the
      CCAAT family, binds to the CFTR promoter and contributes to its transcriptional
      activity. Our data reveal that C/EBPbeta cooperates with USF2 and acts
      antagonistically to YY1 in the control of CFTR expression. Interestingly, YY1, a
      strong repressor, fails to repress the CFTR activation induced by USF2 through
      DNA binding competition. Collectively, the data strongly suggest a model by which
      USF2 functionally interacts with YY1 blocking its inhibitory activity, in favour
      of C/EBPbeta transactivation. Further investigation into the interactions between
      these three proteins revealed that phosphorylation of C/EBPbeta influences the
      DNA occupancy of YY1 and favours the interaction between USF2 and YY1. This
      phosphorylation process has several implications in the CFTR transcriptional
      process, thus evoking an additional layer of complexity to the mechanisms
      influencing CFTR gene regulation.

PMID- 23560078
TI  - Predicting the proteins of Angomonas deanei, Strigomonas culicis and their
      respective endosymbionts reveals new aspects of the trypanosomatidae family.
AB  - Endosymbiont-bearing trypanosomatids have been considered excellent models for
      the study of cell evolution because the host protozoan co-evolves with an
      intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a
      single invertebrate host during their entire life cycle and exhibit special
      characteristics that group them in a particular phylogenetic cluster of the
      Trypanosomatidae family, thus classified as monoxenics. In an effort to better
      understand such symbiotic association, we used DNA pyrosequencing and a reference
      guided assembly to generate reads that predicted 16,960 and 12,162 open reading
      frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei
      (previously named as Crithidia deanei) and Strigomonas culicis (first known as
      Blastocrithidia culicis), respectively. Identification of each ORF was based
      primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing
      getorf from EMBOSS and Newbler 2.6 when necessary. The monoxenic organisms
      revealed conserved housekeeping functions when compared to other trypanosomatids,
      especially compared with Leishmania major. However, major differences were found
      in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar
      structure. The monoxenic organisms also contain a large number of genes for
      cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of
      compartmentalized cysteine proteases in comparison to other TriTryp organisms,
      reflecting adaptations to the presence of the symbiont. The assembled bacterial
      endosymbiont sequences exhibit a high A+T content with a total of 787 and 769
      ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts,
      respectively, and indicate that these organisms hold a common ancestor related to
      the Alcaligenaceae family. Importantly, both symbionts contain enzymes that
      complement essential host cell biosynthetic pathways, such as those for amino
      acid, lipid and purine/pyrimidine metabolism. These findings increase our
      understanding of the intricate symbiotic relationship between the bacterium and
      the trypanosomatid host and provide clues to better understand eukaryotic cell
      evolution.

PMID- 23560080
TI  - Evaluation of lateral spread of transgene expression following subretinal AAV
      mediated gene delivery in dogs.
AB  - Dog models with spontaneously occurring mutations in retinal dystrophy genes are
      an invaluable resource for preclinical development of retinal gene therapy. Adeno
      associated virus (AAV) vectors have been most successful; to target the outer
      retina and RPE they are delivered by subretinal injection, causing a temporary
      retinal detachment with some potential for retinal morbidity. A recent reporter
      gene study using an AAV2/8 vector in dogs reported transgene expression beyond
      the boundary of the subretinal bleb. This could be a desirable feature which
      increases the area of retina treated while minimizing the retinal detachment and
      any associated morbidity. We performed a detailed study of the lateral spread of
      transgene expression beyond the subretinal injection site following subretinally
      delivered AAV vectors in normal dogs. Vectors expressed green fluorescent protein
      (GFP) using a small chicken beta-actin promoter. AAV2/2 (quadruple tyrosine to
      phenylalanine (Y-F) capsid mutant), self-complementary (sc) AAV2/8 (single Y-F
      capsid mutant) and a scAAV2/5 were used. We found that in all eyes GFP expression
      involved retina beyond the initial post-injection subretinal bleb boundary. In
      all eyes there was post-injection spread of the retinal detachment within the
      first 3 days post procedure and prior to retinal reattachment. In 11/16 eyes this
      accounted for the entire "lateral spread" of GFP expression while in 5/16 eyes a
      very slight extension of GFP expression beyond the final boundary of the
      subretinal bleb could be detected. All 3 AAV constructs induced GFP expression in
      the nerve fiber layer with spread to the optic nerve. Patients treated by
      subretinal injection should be monitored for possible expansion of the subretinal
      injection bleb prior to reattachment. Injections in the para-foveal region may
      expand to lead to a foveal detachment that may be undesirable. Cell-specific
      promoters may be required to limit spread of expressed transgene to the brain
      with these AAV serotypes.

PMID- 23560081
TI  - Mycobacterium tuberculosis ClpP proteases are co-transcribed but exhibit
      different substrate specificities.
AB  - Caseinolytic (Clp) proteases are widespread energy-dependent proteases; the
      functional ATP-dependent protease is comprised of multimers of proteolytic and
      regulatory subunits. Mycobacterium tuberculosis has two ClpP proteolytic subunits
      (ClpP1 and ClpP2), with both being essential for growth in vitro. ClpP1 and clpP2
      are arranged in an apparent operon; we demonstrated that the two genes are co
      expressed under normal growth conditions. We identified a single promoter region
      for the clpP1P2 operon; no promoter was detected upstream of clpP2 demonstrating
      that independent expression of clpP1 and clpP2 was highly unlikely. Promoter
      activity was not induced by heat shock or oxidative stress. We identified a
      regulatory region upstream of the promoter with a consensus sequence matching the
      ClgR regulator motif; we determined the limits of the region by mutagenesis and
      confirmed that positive regulation of the promoter occurs in M. tuberculosis. We
      developed a reporter system to monitor ClpP1 and ClpP2 enzymatic activities based
      on LacZ incorporating ssrAtag sequences. We showed that whilst both ClpP1 and
      ClpP2 degrade SsrA-tagged LacZ, ClpP2 (but not ClpP1) degrades untagged proteins.
      Our data suggest that the two proteolytic subunits display different substrate
      specificities and therefore have different, but overlapping roles in M.
      tuberculosis.

PMID- 23560082
TI  - Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve
      development.
AB  - Endocardial to mesenchymal transformation (EMT) is a fundamental cellular process
      required for heart valve formation. Notch, Wnt and Bmp pathways are known to
      regulate this process. To further address how these pathways coordinate in the
      process, we specifically disrupted Notch1 or Jagged1 in the endocardium of mouse
      embryonic hearts and showed that Jagged1-Notch1 signaling in the endocardium is
      essential for EMT and early valvular cushion formation. qPCR and RNA in situ
      hybridization assays reveal that endocardial Jagged1-Notch1 signaling regulates
      Wnt4 expression in the atrioventricular canal (AVC) endocardium and Bmp2 in the
      AVC myocardium. Whole embryo cultures treated with Wnt4 or Wnt inhibitory factor
      1 (Wif1) show that Bmp2 expression in the AVC myocardium is dependent on Wnt
      activity; Wnt4 also reinstates Bmp2 expression in the AVC myocardium of
      endocardial Notch1 null embryos. Furthermore, while both Wnt4 and Bmp2 rescue the
      defective EMT resulting from Notch inhibition, Wnt4 requires Bmp for its action.
      These results demonstrate that Jagged1-Notch1 signaling in endocardial cells
      induces the expression of Wnt4, which subsequently acts as a paracrine factor to
      upregulate Bmp2 expression in the adjacent AVC myocardium to signal EMT.

PMID- 23560083
TI  - Can insects develop resistance to insect pathogenic fungi?
AB  - Microevolutionary adaptations and mechanisms of fungal pathogen resistance were
      explored in a melanic population of the Greater wax moth, Galleria mellonella.
      Under constant selective pressure from the insect pathogenic fungus Beauveria
      bassiana, 25(th) generation larvae exhibited significantly enhanced resistance,
      which was specific to this pathogen and not to another insect pathogenic fungus,
      Metarhizium anisopliae. Defense and stress management strategies of selected
      (resistant) and non-selected (susceptible) insect lines were compared to uncover
      mechanisms underpinning resistance, and the possible cost of those survival
      strategies. We hypothesize that the insects developed a transgenerationally
      primed resistance to the fungus B. bassiana, a costly trait that was achieved not
      by compromising life-history traits but rather by prioritizing and re-allocating
      pathogen-species-specific augmentations to integumental front-line defenses that
      are most likely to be encountered by invading fungi. Specifically during B.
      bassiana infection, systemic immune defenses are suppressed in favour of a more
      limited but targeted repertoire of enhanced responses in the cuticle and
      epidermis of the integument (e.g. expression of the fungal enzyme inhibitor IMPI,
      and cuticular phenoloxidase activity). A range of putative stress-management
      factors (e.g. antioxidants) is also activated during the specific response of
      selected insects to B. bassiana but not M. anisopliae. This too occurs primarily
      in the integument, and probably contributes to antifungal defense and/or helps
      ameliorate the damage inflicted by the fungus or the host's own immune responses.

PMID- 23560084
TI  - New components of Drosophila leg development identified through genome wide
      association studies.
AB  - The adult Drosophila melanogaster body develops from imaginal discs, groups of
      cells set-aside during embryogenesis and expanded in number during larval stages.
      Specification and development of Drosophila imaginal discs have been studied for
      many years as models of morphogenesis. These studies are often based on mutations
      with large developmental effects, mutations that are often lethal in embryos when
      homozygous. Such forward genetic screens can be limited by factors such as early
      lethality and genetic redundancy. To identify additional genes and genetic
      pathways involved in leg imaginal disc development, we employed a Genome Wide
      Association Study utilizing the natural genetic variation in leg proportionality
      found in the Drosophila Genetic Reference Panel fly lines. In addition to
      identifying genes already known to be involved in leg development, we identified
      several genes involved in pathways that had not previously been linked with leg
      development. Several of the genes appear to be involved in signaling activities,
      while others have no known roles at this time. Many of these uncharacterized
      genes are conserved in mammals, so we can now begin to place these genes into
      developmental contexts. Interestingly, we identified five genes which, when their
      function is reduced by RNAi, cause an antenna-to-leg transformation. Our results
      demonstrate the utility of this approach, integrating the tools of quantitative
      and molecular genetics to study developmental processes, and provide new insights
      into the pathways and networks involved in Drosophila leg development.

PMID- 23560085
TI  - A novel PEGylated liposome-encapsulated SANT75 suppresses tumor growth through
      inhibiting hedgehog signaling pathway.
AB  - The Hedgehog (Hh) pathway inhibitors have shown great promise in cancer
      therapeutics. SANT75, a novel compound we previously designed to specially
      inhibit the Smoothened (SMO) protein in the Hh pathway, has greater inhibitory
      potency than many of commonly used Hh inhibitors. However, preclinical studies of
      SANT75 revealed water insolubility and acute toxicity. To overcome these
      limitations, we developed a liposomal formulation of SANT75 and investigated its
      antitumor efficacy in vitro and in vivo. We encapsulated SANT75 into PEGylated
      liposome and the mean particle size distribution and zeta-potential (ZP) of
      liposomes were optimized. Using the Shh-light2 cell and Gli-GFP or Flk-GFP
      transgenic reporter zebrafish, we confirmed that liposome-encapsulated SANT75
      inhibited Hh activity with similar potency as the original SANT75. SANT75
      encapsulated into liposome exerted strong tumor growth-inhibiting effects in
      vitro and in vivo. In addition, the liposomal SANT75 therapy efficiently improved
      the survival time of tumor-bearing mice without obvious systemic toxicity. The
      pathological morphology and immunohistochemistry staining revealed that liposomal
      SANT75 induced tumor cell apoptosis, inhibited tumor angiogenesis as assessed by
      CD31 and down-regulated the expression of Hh target protein Gli-1 in tumor
      tissues. Our findings suggest that liposomal formulated SANT75 has improved
      solubility and bioavailability and should be further developed as a drug
      candidate for treating tumors with abnormally high Hh activity.

PMID- 23560086
TI  - CLL cells respond to B-Cell receptor stimulation with a microRNA/mRNA signature
      associated with MYC activation and cell cycle progression.
AB  - Chronic lymphocytic leukemia (CLL) is a disease with variable clinical outcome.
      Several prognostic factors such as the immunoglobulin heavy chain variable genes
      (IGHV) mutation status are linked to the B-cell receptor (BCR) complex,
      supporting a role for triggering the BCR in vivo in the pathogenesis. The miRNA
      profile upon stimulation and correlation with IGHV mutation status is however
      unknown. To evaluate the transcriptional response of peripheral blood CLL cells
      upon BCR stimulation in vitro, miRNA and mRNA expression was measured using
      hybridization arrays and qPCR. We found both IGHV mutated and unmutated CLL cells
      to respond with increased expression of MYC and other genes associated with BCR
      activation, and a phenotype of cell cycle progression. Genome-wide expression
      studies showed hsa-miR-132-3p/hsa-miR-212 miRNA cluster induction associated with
      a set of downregulated genes, enriched for genes modulated by BCR activation and
      amplified by Myc. We conclude that BCR triggering of CLL cells induces a
      transcriptional response of genes associated with BCR activation, enhanced cell
      cycle entry and progression and suggest that part of the transcriptional profiles
      linked to IGHV mutation status observed in isolated peripheral blood are not cell
      intrinsic but rather secondary to in vivo BCR stimulation.

PMID- 23560087
TI  - Quantitative design of regulatory elements based on high-precision strength
      prediction using artificial neural network.
AB  - Accurate and controllable regulatory elements such as promoters and ribosome
      binding sites (RBSs) are indispensable tools to quantitatively regulate gene
      expression for rational pathway engineering. Therefore, de novo designing
      regulatory elements is brought back to the forefront of synthetic biology
      research. Here we developed a quantitative design method for regulatory elements
      based on strength prediction using artificial neural network (ANN). One hundred
      mutated Trc promoter & RBS sequences, which were finely characterized with a
      strength distribution from 0 to 3.559 (relative to the strength of the original
      sequence which was defined as 1), were used for model training and test. A
      precise strength prediction model, NET90_19_576, was finally constructed with
      high regression correlation coefficients of 0.98 for both model training and
      test. Sixteen artificial elements were in silico designed using this model. All
      of them were proved to have good consistency between the measured strength and
      our desired strength. The functional reliability of the designed elements was
      validated in two different genetic contexts. The designed parts were successfully
      utilized to improve the expression of BmK1 peptide toxin and fine-tune deoxy
      xylulose phosphate pathway in Escherichia coli. Our results demonstrate that the
      methodology based on ANN model can de novo and quantitatively design regulatory
      elements with desired strengths, which are of great importance for synthetic
      biology applications.

PMID- 23560088
TI  - Left ventricular assist device effects on metabolic substrates in the failing
      heart.
AB  - BACKGROUND: Heart failure patients have inadequate nutritional intake and
      alterations in metabolism contributing to an overall energy depleted state. Left
      ventricular assist device (LVAD) support is a common and successful intervention
      in patients with end-stage heart failure. LVAD support leads to alterations in
      cardiac output, functional status, neurohormonal activity and transcriptional
      profiles but the effects of LVADs on myocardial metabolism are unknown. This
      study set out to measure cardiac metabolites in non-failing hearts, failing
      hearts, and hearts post-LVAD support. METHODS: The study population consisted of
      8 non-ischemic failing (at LVAD implant) and 8 post-LVAD hearts, plus 8 non
      failing hearts obtained from the tissue bank at the University of Colorado. NMR
      spectroscopy was utilized to evaluate differences in myocardial energy
      substrates. Paired and non-paired t-tests were used to determine differences
      between the appropriate groups. RESULTS: Glucose and lactate values both
      decreased from non-failing to failing hearts and increased again significantly in
      the (paired) post-LVAD hearts. Glutamine, alanine, and aromatic amino acids
      decreased from non-failing to failing hearts and did not change significantly
      post-LVAD. Total creatine and succinate decreased from non-failing to failing
      hearts and did not change significantly post-LVAD. DISCUSSION: Measured
      metabolites related to glucose metabolism are diminished in failing hearts, but
      recovered their values post-LVAD. This differed from the amino acid levels, which
      decreased in heart failure but did not recover following LVAD. Creatine and the
      citric acid cycle intermediate succinate followed a similar pattern as the amino
      acid levels.

PMID- 23560089
TI  - Intra-tumoral heterogeneity in metastatic potential and survival signaling
      between iso-clonal HCT116 and HCT116b human colon carcinoma cell lines.
AB  - BACKGROUND: Colorectal cancer (CRC) metastasis is a leading cause of cancer
      related deaths in the United States. The molecular mechanisms underlying this
      complex, multi-step pathway are yet to be completely elucidated. Recent reports
      have stressed the importance of intra-tumoral heterogeneity in the development of
      a metastatic phenotype. The purpose of this study was to characterize the intra
      tumoral phenotypic heterogeneity between two iso-clonal human colon cancer
      sublines HCT116 and HCT116b on their ability to undergo metastatic colonization
      and survive under growth factor deprivation stress (GFDS). MATERIALS AND METHODS:
      HCT116 and HCT116b cells were transfected with green fluorescence protein and
      subcutaneously injected into BALB/c nude male mice. Once xenografts were
      established, they were excised and orthotopically implanted into other male
      BALB/c nude mice using microsurgical techniques. Animal tissues were studied for
      metastases using histochemical techniques. Microarray analysis was performed to
      generate gene signatures associated with each subline. In vitro assessment of
      growth factor signaling pathway was performed under GFDS for 3 and 5 days.
      RESULTS: Both HCT116 and HCT116b iso-clonal variants demonstrated 100% primary
      tumor growth, invasion and peritoneal spread. However, HCT116 was highly
      metastatic with 68% metastasis observed in liver and/or lungs compared to 4% in
      HCT116b. Microarray analysis revealed an upregulation of survival and metastatic
      genes in HCT116 cells compared to HCT116b cells. In vitro analysis showed that
      HCT116 upregulated survival and migratory signaling proteins and downregulated
      apoptotic agents under GFDS. However, HCT116b cells effectively showed the
      opposite response under stress inducing cell death. CONCLUSIONS: We demonstrate
      the importance of clonal variation in determining metastatic potential of
      colorectal cancer cells using the HCT116/HCT116b iso-clonal variants in an
      orthotopic metastatic mouse model. Determination of clonal heterogeneity in
      patient tumors can serve as useful tools to identify clinically relevant
      biomarkers for diagnostic and therapeutic assessment of metastatic colorectal
      cancer.

PMID- 23560090
TI  - Bluetongue disease risk assessment based on observed and projected Culicoides
      obsoletus spp. vector densities.
AB  - Bluetongue is an arboviral disease of ruminants causing significant economic
      losses. Our risk assessment is based on the epidemiological key parameter, the
      basic reproduction number. It is defined as the number of secondary cases caused
      by one primary case in a fully susceptible host population, in which values
      greater than one indicate the possibility, i.e., the risk, for a major disease
      outbreak. In the course of the Bluetongue virus serotype 8 (BTV-8) outbreak in
      Europe in 2006 we developed such a risk assessment for the University of
      Veterinary Medicine Vienna, Austria. Basic reproduction numbers were calculated
      using a well-known formula for vector-borne diseases considering the population
      densities of hosts (cattle and small ruminants) and vectors (biting midges of the
      Culicoides obsoletus spp.) as well as temperature dependent rates. The latter
      comprise the biting and mortality rate of midges as well as the reciprocal of the
      extrinsic incubation period. Most important, but generally unknown, is the spatio
      temporal distribution of the vector density. Therefore, we established a
      continuously operating daily monitoring to quantify the seasonal cycle of the
      vector population by a statistical model. We used cross-correlation maps and
      Poisson regression to describe vector densities by environmental temperature and
      precipitation. Our results comprise time series of observed and simulated
      Culicoides obsoletus spp. counts as well as basic reproduction numbers for the
      period 2009-2011. For a spatio-temporal risk assessment we projected our results
      from the location of Vienna to the entire region of Austria. We compiled both
      daily maps of vector densities and the basic reproduction numbers, respectively.
      Basic reproduction numbers above one were generally found between June and August
      except in the mountainous regions of the Alps. The highest values coincide with
      the locations of confirmed BTV cases.

PMID- 23560091
TI  - Transforming growth factor beta1 induces the expression of collagen type I by DNA
      methylation in cardiac fibroblasts.
AB  - Transforming growth factor-beta (TGF-beta), a key mediator of cardiac fibroblast
      activation, has a major influence on collagen type I production. However, the
      epigenetic mechanisms by which TGF-beta induces collagen type I alpha 1 (COL1A1)
      expression are not fully understood. This study was designed to examine whether
      or not DNA methylation is involved in TGF-beta-induced COL1A1 expression in
      cardiac fibroblasts. Cells isolated from neonatal Sprague-Dawley rats were
      cultured and stimulated with TGF-beta1. The mRNA levels of COL1A1 and DNA
      methyltransferases (DNMTs) were determined via quantitative polymerase chain
      reaction and the protein levels of collagen type I were determined via Western
      blot as well as enzyme-linked immunosorbent assay. The quantitative methylation
      of the COL1A1 promoter region was analyzed using the MassARRAY platform of
      Sequenom. Results showed that TGF-beta1 upregulated the mRNA expression of COL1A1
      and induced the synthesis of cell-associated and secreted collagen type I in
      cardiac fibroblasts. DNMT1 and DNMT3a expressions were significantly
      downregulated and the global DNMT activity was inhibited when treated with 10
      ng/mL of TGF-beta1 for 48 h. TGF-beta1 treatment resulted in a significant
      reduction of the DNA methylation percentage across multiple CpG sites in the rat
      COL1A1 promoter. Thus, TGF-beta1 can induce collagen type I expression through
      the inhibition of DNMT1 and DNMT3a expressions as well as global DNMT activity,
      thereby resulting in DNA demethylation of the COL1A1 promoter. These findings
      suggested that the DNMT-mediated DNA methylation is an important mechanism in
      regulating the TGF-beta1-induced COL1A1 gene expression.

PMID- 23560092
TI  - Traditional Chinese medicine in cancer care: a review of controlled clinical
      studies published in chinese.
AB  - BACKGROUND: Traditional Chinese medicine (TCM) has been widely applied for cancer
      care in China. There have been a large number of controlled clinical studies
      published in Chinese literature, yet no systematic searching and analysis has
      been done. This study summarizes the current evidence of controlled clinical
      studies of TCM for cancer. METHODS: We searched all the controlled clinical
      studies of TCM therapies for all kinds of cancers published in Chinese in four
      main Chinese electronic databases from their inception to November 2011. We
      bibliometrically analyzed the included studies and assessed the reporting
      quality. RESULTS: A total of 2964 reports (involving 253,434 cancer patients)
      including 2385 randomized controlled trials and 579 non-randomized controlled
      studies were included. The top seven cancer types treated were lung cancer, liver
      cancer, stomach cancer, breast cancer, esophagus cancer, colorectal cancer and
      nasopharyngeal cancer by both study numbers and case numbers. The majority of
      studies (72%) applied TCM therapy combined with conventional treatment, whilst
      fewer (28%) applied only TCM therapy in the experimental groups. Herbal medicine
      was the most frequently applied TCM therapy (2677 studies, 90.32%). The most
      frequently reported outcome was clinical symptom improvement (1667 studies,
      56.24%) followed by biomarker indices (1270 studies, 42.85%), quality of life
      (1129 studies, 38.09%), chemo/radiotherapy induced side effects (1094 studies,
      36.91%), tumor size (869 studies, 29.32%) and safety (547 studies, 18.45%).
      Completeness and adequacy of reporting appeared to improve with time.
      CONCLUSIONS: Data from controlled clinical studies of TCM therapies in cancer
      treatment is substantial, and different therapies are applied either as
      monotherapy or in combination with conventional medicine. Reporting of controlled
      clinical studies should be improved based on the CONSORT and TREND Statements in
      future. Further studies should address the most frequently used TCM therapy for
      common cancers and outcome measures should address survival, relapse/metastasis
      and quality of life.

PMID- 23560093
TI  - Age-dependent effects of A53T alpha-synuclein on behavior and dopaminergic
      function.
AB  - Expression of A53T mutant human alpha-synuclein under the mouse prion promoter is
      among the most successful transgenic models of Parkinson's disease. Accumulation
      of A53T alpha-synuclein causes adult mice to develop severe motor impairment
      resulting in early death at 8-12 months of age. In younger, pre-symptomatic
      animals, altered motor activity and anxiety-like behaviors have also been
      reported. These behavioral changes, which precede severe neuropathology, may stem
      from non-pathological functions of alpha-synuclein, including modulation of
      monoamine neurotransmission. Our analysis over the adult life-span of motor
      activity, anxiety-like, and depressive-like behaviors identifies perturbations
      both before and after the onset of disease. Young A53T mice had increased
      distribution of the dopamine transporter (DAT) to the membrane that was
      associated with increased striatal re-uptake function. DAT function decreased
      with aging, and was associated with neurochemical alterations that included
      increased expression of beta-synuclein and gamma synuclein. Prior to
      normalization of dopamine uptake, transient activation of Tau kinases and
      hyperphosphorylation of Tau in the striatum were also observed. Aged A53T mice
      had reduced neuron counts in the substantia nigra pars compacta, yet striatal
      medium spiny neuron dendritic spine density was largely maintained. These
      findings highlight the involvement of the synuclein family of proteins and
      phosphorylation of Tau in the response to dopaminergic dysfunction of the
      nigrostriatal pathway.

PMID- 23560094
TI  - Study of global transcriptional changes of N-GlcNAc2 proteins-producing T24
      bladder carcinoma cells under glucose deprivation.
AB  - Increased levels of N-linked (beta-N- acetylglucosamine)2 [N-GlcNAc2]-modified
      proteins have been recognized to be an effective response to glucose deprivation.
      In the first step of this study, using a next generation sequencer, we
      investigated the global transcriptional changes induced by glucose deprivation in
      a T24 bladder carcinoma cell line, producing N-GlcNAc2-modified proteins under
      glucose deprivation. Our transcriptome analysis revealed significant up
      regulation of the UDP-GlcNAc biosynthesis pathway and unfolded protein response
      genes, and down-regulation of G2/M transition-related genes containing mitotic
      kinases. Our biological analysis confirmed that N-GlcNAc2-modified proteins were
      localized with BiP proteins in the ER. G2/M arrest was caused by glucose
      deprivation in T24 cells. Moreover, the knockdown of unfolded protein response
      genes induced the expressional recovery of mitotic kinases under glucose
      deprivation. Taken together, our results suggest N-GlcNAc2-modified proteins
      produced under glucose deprivation caused unfolded protein response in the ER,
      and that this response induced G2/M arrest.

PMID- 23560095
TI  - BAFF receptor mAb treatment ameliorates development and progression of
      atherosclerosis in hyperlipidemic ApoE(-/-) mice.
AB  - AIMS: Option to attenuate atherosclerosis by depleting B2 cells is currently
      limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present
      study we evaluated the capacity of a monoclonal antibody to B cell activating
      factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent
      both development and progression of atherosclerosis in the ApoE(-/-) mouse.
      METHODS AND RESULTS: To determine whether the BAFFR antibody prevents
      atherosclerosis development, we treated ApoE(-/-) mice with the antibody while
      feeding them a high fat diet (HFD) for 8 weeks. Mature CD93(-) CD19(+) B2 cells
      were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA
      expression decreased while B1a cells and non-B cells were spared. Atherosclerosis
      was ameliorated in the hyperlipidemic mice and CD19(+) B cells, CD4(+) and CD8(+)
      T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory
      cytokines, IL1beta, TNFalpha, and IFNgamma in the lesions were also reduced,
      while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins
      were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine
      whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first
      fed ApoE(-/-) mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody
      treatment for a further 6 week-HFD. CD93(-) CD19(+) B2 cells were selectively
      decreased and atherosclerotic lesions were reduced by this treatment. CONCLUSION:
      Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing
      B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis
      development and progression in hyperlipidemic ApoE(-/-) mice. Our findings have
      potential for clinical translation to manage atherosclerosis-based cardiovascular
      diseases.

PMID- 23560096
TI  - Genetic variations in SMAD7 are associated with colorectal cancer risk in the
      colon cancer family registry.
AB  - BACKGROUND: Recent genome-wide studies identified a risk locus for colorectal
      cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the
      association between SMAD7 SNPs and colorectal cancer risk in the multi-center
      Colon Cancer Family Registry. MATERIALS AND METHODS: 23 tagging SNPs in the SMAD7
      gene were genotyped among 1,592 population-based and 253 clinic-based families.
      The SNP-colorectal cancer associations were assessed in multivariable conditional
      logistic regression. RESULTS: Among the population-based families, both SNPs
      rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49), and rs11874392
      (odds ratio, 0.80; 95% confidence interval, 0.70-0.92) were associated with risk
      of colorectal cancer. These associations were similar among the population- and
      the clinic-based families, though they were significant only among the former.
      Marginally significant differences in the SNP-colorectal cancer associations were
      observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body
      mass index, and history of polyps. CONCLUSIONS: SMAD7 SNPs were associated with
      colorectal cancer risk in the Colon Cancer Family Registry. There was evidence
      suggesting that the association between rs12953717 and colorectal cancer risk may
      be modified by factors such as smoking and use of nonsteroidal anti-inflammatory
      drugs.

PMID- 23560097
TI  - Origins of balance disorders during a daily living movement in obese: can
      biomechanical factors explain everything?
AB  - Obese people suffer from postural deficits and are more subject to falls than
      their lean counterpart. To improve prevention and post-fall rehabilitation
      programs, it seems important to better understand the posturo-kinetic disorders
      in daily life situations by determining the contribution of some key factors,
      mainly morphological characteristics and physical activity level, in the
      apparition of these disorders. Twelve severe android obese and eight healthy non
      obese adults performed a reaching task mobilizing the whole body. To further
      determine the origin of the postural and motor behavior differences, non obese
      individuals also performed an experimental session with additional constraints
      which simulated some of the obese morphological characteristics. Impact of the
      sedentary lifestyle was also studied by dissociation of the obese in two
      subgroups: physically " active " and physically " inactive ". Movement kinetics
      and kinematics were characterized with an optoelectronic system synchronized to a
      force platform. The mechanical equilibrium pattern was evaluated through the
      displacements of the Centre of Mass (CoM) and the centre of foot pressure within
      the Base of Support (BoS). Results showed that obesity decreased movement speed
      (~-23%, p<0.01), strongly increased CoM displacement (~+30%, p<0.05) and induced
      an important spatio-temporal desynchronization (~+40%, p<0.05) of the focal and
      postural components of the movement during the transition between the descending
      and ascending movements. The role of some morphological characteristics and of
      physical activity on obese patients' postural control disorder is discussed and
      set back in the more general context of overall factors contributing to postural
      deficits with obesity.

PMID- 23560099
TI  - Ankylosaur remains from the early cretaceous (valanginian) of northwestern
      Germany.
AB  - A fragmentary cervico-pectoral lateral spine and partial humerus of an ankylosaur
      from the Early Cretaceous (early Valanginian) of Gronau in Westfalen,
      northwestern Germany, are described. The spine shows closest morphological
      similarities to the characteristic cervical and pectoral spines of Hylaeosaurus
      armatus from the late Valanginian of England. An extensive comparison of distal
      humeri among thyreophoran dinosaurs supports systematic differences in the
      morphology of the distal condyli between Ankylosauria and Stegosauria and a
      referral of the Gronau specimen to the former. The humerus fragment indicates a
      rather small individual, probably in the size range of H. armatus, and both
      specimens are determined herein as ?Hylaeosaurus sp.. A short overview of other
      purported ankylosaur material from the Berriasian-Valanginian of northwest
      Germany shows that, aside from the material described herein, only tracks can be
      attributed to this clade with confidence at present.

PMID- 23560098
TI  - Adaptive filtering methods for identifying cross-frequency couplings in human
      EEG.
AB  - Oscillations have been increasingly recognized as a core property of neural
      responses that contribute to spontaneous, induced, and evoked activities within
      and between individual neurons and neural ensembles. They are considered as a
      prominent mechanism for information processing within and communication between
      brain areas. More recently, it has been proposed that interactions between
      periodic components at different frequencies, known as cross-frequency couplings,
      may support the integration of neuronal oscillations at different temporal and
      spatial scales. The present study details methods based on an adaptive frequency
      tracking approach that improve the quantification and statistical analysis of
      oscillatory components and cross-frequency couplings. This approach allows for
      time-varying instantaneous frequency, which is particularly important when
      measuring phase interactions between components. We compared this adaptive
      approach to traditional band-pass filters in their measurement of phase-amplitude
      and phase-phase cross-frequency couplings. Evaluations were performed with
      synthetic signals and EEG data recorded from healthy humans performing an
      illusory contour discrimination task. First, the synthetic signals in conjunction
      with Monte Carlo simulations highlighted two desirable features of the proposed
      algorithm vs. classical filter-bank approaches: resilience to broad-band noise
      and oscillatory interference. Second, the analyses with real EEG signals revealed
      statistically more robust effects (i.e. improved sensitivity) when using an
      adaptive frequency tracking framework, particularly when identifying phase
      amplitude couplings. This was further confirmed after generating surrogate
      signals from the real EEG data. Adaptive frequency tracking appears to improve
      the measurements of cross-frequency couplings through precise extraction of
      neuronal oscillations.

PMID- 23560100
TI  - Neural effects of auditory distraction on visual attention in schizophrenia.
AB  - Sensory flooding, particularly during auditory stimulation, is a common problem
      for patients with schizophrenia. The functional consequences of this impairment
      during cross-modal attention tasks, however, are unclear. The purpose of this
      study was to examine how auditory distraction differentially affects task
      associated response during visual attention in patients and healthy controls. To
      that end, 21 outpatients with schizophrenia and 23 healthy comparison subjects
      performed a visual attention task in the presence or absence of distracting,
      environmentally relevant "urban" noise while undergoing functional magnetic
      resonance imaging at 3T. The task had two conditions (difficult and easy); task
      related neural activity was defined as difficult - easy. During task performance,
      a significant distraction (noise or silence) by group (patient or control)
      interaction was observed in the left dorsolateral prefrontal cortex, right
      hippocampus, left temporoparietal junction, and right fusiform gyrus, with
      patients showing relative hypoactivation during noise compared to controls. In
      patients, the ability to recruit the dorsolateral prefrontal cortex during the
      task in noise was negatively correlated with the effect of noise on reaction
      time. Clinically, the ability to recruit the fusiform gyrus during the task in
      noise was negatively correlated with SANS affective flattening score, and
      hippocampal recruitment during the task in noise was positively correlated with
      global functioning. In conclusion, schizophrenia may be associated with
      abnormalities in neural response during visual attention tasks in the presence of
      cross-modal noise distraction. These response differences may predict global
      functioning in the illness, and may serve as a biomarker for therapeutic
      development.

PMID- 23560102
TI  - Geographic variation in chin shape challenges the universal facial attractiveness
      hypothesis.
AB  - The universal facial attractiveness (UFA) hypothesis proposes that some facial
      features are universally preferred because they are reliable signals of mate
      quality. The primary evidence for this hypothesis comes from cross-cultural
      studies of perceived attractiveness. However, these studies do not directly
      address patterns of morphological variation at the population level. An
      unanswered question is therefore: Are universally preferred facial phenotypes
      geographically invariant, as the UFA hypothesis implies? The purpose of our study
      is to evaluate this often overlooked aspect of the UFA hypothesis by examining
      patterns of geographic variation in chin shape. We collected symphyseal outlines
      from 180 recent human mandibles (90 male, 90 female) representing nine geographic
      regions. Elliptical Fourier functions analysis was used to quantify chin shape,
      and principle components analysis was used to compute shape descriptors. In
      contrast to the expectations of the UFA hypothesis, we found significant
      geographic differences in male and female chin shape. These findings are
      consistent with region-specific sexual selection and/or random genetic drift, but
      not universal sexual selection. We recommend that future studies of facial
      attractiveness take into consideration patterns of morphological variation within
      and between diverse human populations.

PMID- 23560101
TI  - Psychosocial working conditions and cognitive complaints among Swedish employees.
AB  - BACKGROUND: Cognitive complaints involving problems with concentration, memory,
      decision-making and thinking are relatively common in the work force. The
      sensitivity of both subjective and objective cognitive functioning to common
      psychiatric conditions, stress levels and to cognitive load makes it plausible
      that psychosocial working conditions play a role in cognitive complaints. Thus,
      this study aimed to test the associations between psychosocial work factors and
      cognitive complaints in nationally representative samples of the Swedish work
      force. Cross-sectional (n = 9751) and prospective (n = 3644; two time points two
      years apart) sequential multiple regression analyses were run, adjusting for
      general confounders, depressive- and sleeping problems. Additional prospective
      analyses were run adjusting for baseline cognitive complaints. CROSS/SECTIONAL
      RESULTS: High quantitative demands, information and communication technology
      (ICT) demands, under qualification and conflicts were positively associated with
      cognitive complaints, while social support, good resources at work and over
      qualification were negatively associated with cognitive complaints in all models.
      Skill discretion and decision authority were weakly associated with cognitive
      complaints. Conflicts were more strongly associated with cognitive complaints in
      women than in men, after adjustment for general confounders. PROSPECTIVE RESULTS:
      Quantitative job demands, ICT demands and under qualification were positively
      associated with future cognitive complaints in all models, including when
      adjusted for baseline cognitive complaints. Decision authority was weakly
      positively associated with future cognitive complaints, only after adjustment for
      depressive- and sleeping problems respectively. Social support was negatively
      associated with future cognitive complaints after adjustment for general
      confounders and baseline cognitive complaints. Skill discretion and resources
      were negatively associated with future cognitive complaints after adjustment for
      general confounders. The associations between quantitative demands and future
      cognitive complaints were stronger in women. DISCUSSION/CONCLUSIONS: The findings
      indicate that psychosocial working conditions should be taken into account when
      considering cognitive complaints among employees.

PMID- 23560103
TI  - Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance
      lacking? a systematic review.
AB  - BACKGROUND: Patient reported outcomes (PROs) are increasingly assessed in
      clinical trials, and guidelines are available to inform the design and reporting
      of such trials. However, researchers involved in PRO data collection report that
      specific guidance on 'in-trial' activity (recruitment, data collection and data
      inputting) and the management of 'concerning' PRO data (i.e., data which raises
      concern for the well-being of the trial participant) appears to be lacking. The
      purpose of this review was to determine the extent and nature of published
      guidelines addressing these areas. METHODS AND FINDINGS: Systematic review of
      1,362 articles identified 18 eligible papers containing 'in-trial' guidelines.
      Two independent authors undertook a qualitative content analysis of the selected
      papers. Guidelines presented in each of the articles were coded according to an a
      priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86
      0.97), and validity (<2% residual category coding). The majority of guidelines
      present were concerned with 'pre-trial' activities (72%), for example, outcome
      measure selection and study design issues, or 'post-trial' activities (16%) such
      as data analysis, reporting and interpretation. 'In-trial' guidelines represented
      9.2% of all guidance across the papers reviewed, with content primarily focused
      on compliance, quality control, proxy assessment and reporting of data
      collection. There were no guidelines surrounding the management of concerning PRO
      data. CONCLUSIONS: The findings highlight there are minimal in-trial guidelines
      in publication regarding PRO data collection and management in clinical trials.
      No guidance appears to exist for researchers involved with the handling of
      concerning PRO data. Guidelines are needed, which support researchers to manage
      all PRO data appropriately and which facilitate unbiased data collection.

PMID- 23560104
TI  - Pattern-triggered immunity suppresses programmed cell death triggered by
      fumonisin b1.
AB  - Programmed cell death (PCD) is a crucial process for plant innate immunity and
      development. In plant innate immunity, PCD is believed to prevent the spread of
      pathogens from the infection site. Although proper control of PCD is important
      for plant fitness, we have limited understanding of the molecular mechanisms
      regulating plant PCD. Plant innate immunity triggered by recognition of effectors
      (effector-triggered immunity, ETI) is often associated with PCD. However pattern
      triggered immunity (PTI), which is triggered by recognition of elicitors called
      microbe-associated molecular patterns (MAMPs), is not. Therefore we hypothesized
      that PTI might suppress PCD. Here we report that PCD triggered by the mycotoxin
      fumonisin B1 (FB1) can be suppressed by PTI in Arabidopsis. FB1-triggered cell
      death was suppressed by treatment with the MAMPs flg22 (a part of bacterial
      flagellin) or elf18 (a part of the bacterial elongation factor EF-Tu) but not
      chitin (a component of fungal cell walls). Although plant hormone signaling is
      associated with PCD and PTI, both FB1-triggered cell death and suppression of
      cell death by flg22 treatment were still observed in mutants deficient in
      jasmonic acid (JA), ethylene (ET) and salicylic acid (SA) signaling. The MAP
      kinases MPK3 and MPK6 are transiently activated and inactivated within one hour
      during PTI. We found that FB1 activated MPK3 and MPK6 about 36-48 hours after
      treatment. Interestingly, this late activation was attenuated by flg22 treatment.
      These results suggest that PTI suppression of FB1-triggered cell death may
      involve suppression of MPK3/MPK6 signaling but does not require JA/ET/SA
      signaling.

PMID- 23560105
TI  - The evolution of an osmotically inducible dps in the genus Streptomyces.
AB  - Dps proteins are found almost ubiquitously in bacterial genomes and there is now
      an appreciation of their multifaceted roles in various stress responses. Previous
      studies have shown that this family of proteins assemble into dodecamers and
      their quaternary structure is entirely critical to their function. Moreover, the
      numbers of dps genes per bacterial genome is variable; even amongst closely
      related species - however, for many genera this enigma is yet to be
      satisfactorily explained. We reconstruct the most probable evolutionary history
      of Dps in Streptomyces genomes. Typically, these bacteria encode for more than
      one Dps protein. We offer the explanation that variation in the number of dps per
      genome among closely related Streptomyces can be explained by gene duplication or
      lateral acquisition, and the former preceded a subsequent shift in expression
      patterns for one of the resultant paralogs. We show that the genome of S.
      coelicolor encodes for three Dps proteins including a tailless Dps. Our in vivo
      observations show that the tailless protein, unlike the other two Dps in S.
      coelicolor, does not readily oligomerise. Phylogenetic and bioinformatic analyses
      combined with expression studies indicate that in several Streptomyces species at
      least one Dps is significantly over-expressed during osmotic shock, but the
      identity of the ortholog varies. In silico analysis of dps promoter regions
      coupled with gene expression studies of duplicated dps genes shows that
      paralogous gene pairs are expressed differentially and this correlates with the
      presence of a sigB promoter. Lastly, we identify a rare novel clade of Dps and
      show that a representative of these proteins in S. coelicolor possesses a
      dodecameric quaternary structure of high stability.

PMID- 23560107
TI  - Unveiling the diet of elusive rainforest herbivores in next generation sequencing
      era? The tapir as a case study.
AB  - Characterizing the trophic relationships between large herbivores and the
      outstanding plant diversity in rainforest is a major challenge because of their
      elusiveness. This is crucial to understand the role of these herbivores in the
      functioning of the rainforest ecosystems. We tested a non-invasive approach based
      on the high-throughput sequencing of environmental samples using small plant
      plastid sequences (the trnL P6 loop) and ribosomal ITS1 primers, referred to as
      DNA metabarcoding, to investigate the diet of the largest neotropical herbivore,
      the lowland tapir. Sequencing was performed on plant DNA extracted from tapir
      faeces collected at the Nouragues station, a protected area of French Guiana. In
      spite of a limited sampling, our approach reliably provided information about the
      lowland tapir's diet at this site. Indeed, 95.1% and 74.4% of the plant families
      and genera identified thanks to the trnL P6 loop, respectively, matched with taxa
      already known to be consumed by tapirs. With this approach we were able to show
      that two families and eight new genera are also consumed by the lowland tapir.
      The taxonomic resolution of this method is limited to the plant family and
      genera. Complementary barcodes, such as a small portion of ITS1, can be used to
      efficiently narrow identifications down to the species in some problematic
      families. We will discuss the remaining limitations of this approach and how
      useful it is at this stage to unravel the diet of elusive rainforest herbivores
      and better understand their role as engineers of the ecosystem.

PMID- 23560106
TI  - Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory
      and deficit in fear conditioning.
AB  - Glutamate delta-1 (GluD1) receptors are expressed throughout the forebrain during
      development with high levels in the hippocampus during adulthood. We have
      recently shown that deletion of GluD1 receptor results in aberrant emotional and
      social behaviors such as hyperaggression and depression-like behaviors and social
      interaction deficits. Additionally, abnormal expression of synaptic proteins was
      observed in amygdala and prefrontal cortex of GluD1 knockout mice (GluD1 KO).
      However the role of GluD1 in learning and memory paradigms remains unknown. In
      the present study we evaluated GluD1 KO in learning and memory tests. In the
      eight-arm radial maze GluD1 KO mice committed fewer working memory errors
      compared to wildtype mice but had normal reference memory. Enhanced working
      memory in GluD1 KO was also evident by greater percent alternation in the
      spontaneous Y-maze test. No difference was observed in object recognition memory
      in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no
      difference in acquisition but had longer latency to find the platform in the
      reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear
      conditioning but had normal latent inhibition. The deficit in contextual fear
      conditioning was reversed by D-Cycloserine (DCS) treatment. GluD1 KO mice were
      also found to be more sensitive to foot-shock compared to wildtype. We further
      studied molecular changes in the hippocampus, where we found lower levels of
      GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in
      GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95)
      and lower glutamate decarboxylase 67 (GAD67) expression in GluD1 KO. We propose
      that GluD1 is crucial for normal functioning of synapses and absence of GluD1
      leads to specific abnormalities in learning and memory. These findings provide
      novel insights into the role of GluD1 receptors in the central nervous system.

PMID- 23560108
TI  - Space-time clustering of non-hodgkin lymphoma using residential histories in a
      Danish case-control study.
AB  - Non-Hodgkin lymphoma (NHL) is a frequent cancer and incidence rates have
      increased markedly during the second half of the 20(th) century; however, the few
      established risk factors cannot explain this rise and still little is known about
      the aetiology of NHL. Spatial analyses have been applied in an attempt to
      identify environmental risk factors, but most studies do not take human mobility
      into account. The aim of this study was to identify clustering of NHL in space
      and time in Denmark, using 33 years of residential addresses. We utilised the
      nation-wide Danish registers and unique personal identification number that all
      Danish citizens have to conduct a register-based case-control study of 3210 NHL
      cases and two independent control groups of 3210 each. Cases were identified in
      the Danish Cancer Registry and controls were matched by age and sex and randomly
      selected from the Civil Registration System. Residential addresses of cases and
      controls from 1971 to 2003 were collected from the Civil Registration System and
      geocoded. Data on pervious hospital diagnoses and operations were obtained from
      the National Patient Register. We applied the methods of the newly developed Q
      statistics to identify space-time clustering of NHL. All analyses were conducted
      with each of the two control groups, and we adjusted for previous history of
      autoimmune disease, HIV/AIDS or organ transplantation. Some areas with
      statistically significant clustering were identified; however, results were not
      consistent across the two control groups; thus we interpret the results as chance
      findings. We found no evidence for clustering of NHL in space and time using 33
      years of residential histories, suggesting that if the rise in incidence of NHL
      is a result of risk factors that vary across space and time, the spatio-temporal
      variation of such factors in Denmark is too small to be detected with the applied
      method.

PMID- 23560109
TI  - Isolation and characterisation of 1-alkyl-3-methylimidazolium chloride ionic
      liquid-tolerant and biodegrading marine bacteria.
AB  - The aim of this study was to isolate and identify marine-derived bacteria which
      exhibited high tolerance to, and an ability to biodegrade, 1-alkyl-3
      methylimidazolium chloride ionic liquids. The salinity and hydrocarbon load of
      some marine environments may induce selective pressures which enhance the ability
      of microbes to grow in the presence of these liquid salts. The isolates obtained
      in this study generally showed a greater ability to grow in the presence of the
      selected ionic liquids compared to microorganisms described previously, with two
      marine-derived bacteria, Rhodococcus erythropolis and Brevibacterium sanguinis
      growing in concentrations exceeding 1 M 1-ethyl-3-methylimidazolium chloride. The
      ability of these bacteria to degrade the selected ionic liquids was assessed
      using High Performance Liquid Chromatography (HPLC), and three were shown to
      degrade the selected ionic liquids by up to 59% over a 63-day test period. These
      bacterial isolates represent excellent candidates for further potential
      applications in the bioremediation of ionic liquid-containing waste or following
      accidental environmental exposure.

PMID- 23560110
TI  - The ATP-binding cassette transporter ABCB19 regulates postembryonic organ
      separation in Arabidopsis.
AB  - The phytohormone auxin plays a critical role in plant development, including
      embryogenesis, organogenesis, tropism, apical dominance and in cell growth,
      division, and expansion. In these processes, the concentration gradient of auxin,
      which is established by polar auxin transport mediated by PIN-FORMED (PIN)
      proteins and several ATP-binding cassette/multi-drug resistance/P-glycoprotein
      (ABCB/MDR/PGP) transporters, is a crucial signal. Here, we characterized the
      function of ABCB19 in the control of Arabidopsis organ boundary development. We
      identified a new abcb19 allele, abcb19-5, which showed stem-cauline leaf and stem
      pedicel fusion defects. By virtue of the DII-VENUS marker, the auxin level was
      found to be increased at the organ boundary region in the inflorescence apex. The
      expression of CUP-SHAPED COTYLEDON2 (CUC2) was decreased, while no obvious change
      in the expression of CUC3 was observed, in abcb19. In addition, the fusion
      defects were greatly enhanced in cuc3 abcb19-5, which was reminiscent of cuc2
      cuc3. We also found that some other organ boundary genes, such as LOF1/2 were
      down-regulated in abcb19. Together, these results reveal a new aspect of auxin
      transporter ABCB19 function, which is largely dependent on the positive
      regulation of organ boundary genes CUC2 and LOFs at the postembryonic organ
      boundary.

PMID- 23560111
TI  - Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell
      Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.
AB  - In acute myeloid leukemia (AML), the chances of achieving disease-free survival
      are low. Studies have demonstrated a supportive role of endothelial cells (ECs)
      in normal hematopoiesis. Here we show that similar intercellular relationships
      exist in leukemia. We demonstrate that leukemia cells themselves initiate these
      interactions by directly modulating the behavior of resting ECs through the
      induction of EC activation. In this inflammatory state, activated ECs induce the
      adhesion of a sub-set of leukemia cells through the cell adhesion molecule E
      selectin. These adherent leukemia cells are sequestered in a quiescent state and
      are unaffected by chemotherapy. The ability of adherent cells to later detach and
      again become proliferative following exposure to chemotherapy suggests a role of
      this process in relapse. Interestingly, differing leukemia subtypes modulate this
      process to varying degrees, which may explain the varied response of AML patients
      to chemotherapy and relapse rates. Finally, because leukemia cells themselves
      induce EC activation, we postulate a positive-feedback loop in leukemia that
      exists to support the growth and relapse of the disease. Together, the data
      defines a new mechanism describing how ECs and leukemia cells interact during
      leukemogenesis, which could be used to develop novel treatments for those with
      AML.

PMID- 23560112
TI  - Diet-induced obesity promotes colon tumor development in azoxymethane-treated
      mice.
AB  - Obesity is an important risk factor for colon cancer in humans, and numerous
      studies have shown that a high fat diet enhances colon cancer development. As
      both increased adiposity and high fat diet can promote tumorigenesis, we examined
      the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor
      development. C57BL/6J male mice were fed regular chow or high fat diet for 8
      weeks. Diets were either maintained or switched resulting in four experimental
      groups: regular chow (R), high fat diet (H), regular chow switched to high fat
      diet (RH), and high fat diet switched to regular chow (HR). Mice were then
      administered azoxymethane to induce colon tumors. Tumor incidence and
      multiplicity were dramatically smaller in the R group relative to all groups that
      received high fat diet at any point. The effect of obesity on colon tumors could
      not be explained by differences in aberrant crypt foci number. Moreover, diet did
      not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor
      alpha, interleukin-6, interleukin-1beta, and interferon-gamma, which were
      measured immediately after azoxymethane treatment. Crypt apoptosis and
      proliferation, which were measured at the same time, were increased in the HR
      relative to all other groups. Our results suggest that factors associated with
      obesity - independently of ongoing high fat diet and obesity - promote tumor
      development because HR group animals had significantly more tumors than R group,
      and these mice were fed the same regular chow throughout the entire carcinogenic
      period. Moreover, there was no difference in the number of aberrant crypt foci
      between these groups, and thus the effect of obesity appears to be on subsequent
      stages of tumor development when early preneoplastic lesions transition into
      adenomas.

PMID- 23560113
TI  - The development of indonesian online game addiction questionnaire.
AB  - Online game is an increasingly popular source of entertainment for all ages, with
      relatively prevalent negative consequences. Addiction is a problem that has
      received much attention. This research aims to develop a measure of online game
      addiction for Indonesian children and adolescents. The Indonesian Online Game
      Addiction Questionnaire draws from earlier theories and research on the internet
      and game addiction. Its construction is further enriched by including findings
      from qualitative interviews and field observation to ensure appropriate
      expression of the items. The measure consists of 7 items with a 5-point Likert
      Scale. It is validated by testing 1,477 Indonesian junior and senior high school
      students from several schools in Manado, Medan, Pontianak, and Yogyakarta. The
      validation evidence is shown by item-total correlation and criterion validity.
      The Indonesian Online Game Addiction Questionnaire has good item-total
      correlation (ranging from 0.29 to 0.55) and acceptable reliability (alpha =
      0.73). It is also moderately correlated with the participant's longest time
      record to play online games (r = 0.39; p<0.01), average days per week in playing
      online games (rho = 0.43; p<0.01), average hours per days in playing online games
      (rho = 0.41; p<0.01), and monthly expenditure for online games (rho = 0.30;
      p<0.01). Furthermore, we created a clinical cut-off estimate by combining
      criteria and population norm. The clinical cut-off estimate showed that the score
      of 14 to 21 may indicate mild online game addiction, and the score of 22 and
      above may indicate online game addiction. Overall, the result shows that
      Indonesian Online Game Addiction Questionnaire has sufficient psychometric
      property for research use, as well as limited clinical application.

PMID- 23560114
TI  - Plant trait-species abundance relationships vary with environmental properties in
      subtropical forests in eastern china.
AB  - Understanding how plant trait-species abundance relationships change with a range
      of single and multivariate environmental properties is crucial for explaining
      species abundance and rarity. In this study, the abundance of 94 woody plant
      species was examined and related to 15 plant leaf and wood traits at both local
      and landscape scales involving 31 plots in subtropical forests in eastern China.
      Further, plant trait-species abundance relationships were related to a range of
      single and multivariate (PCA axes) environmental properties such as air humidity,
      soil moisture content, soil temperature, soil pH, and soil organic matter,
      nitrogen (N) and phosphorus (P) contents. At the landscape scale, plant maximum
      height, and twig and stem wood densities were positively correlated, whereas mean
      leaf area (MLA), leaf N concentration (LN), and total leaf area per twig size
      (TLA) were negatively correlated with species abundance. At the plot scale, plant
      maximum height, leaf and twig dry matter contents, twig and stem wood densities
      were positively correlated, but MLA, specific leaf area, LN, leaf P concentration
      and TLA were negatively correlated with species abundance. Plant trait-species
      abundance relationships shifted over the range of seven single environmental
      properties and along multivariate environmental axes in a similar way. In
      conclusion, strong relationships between plant traits and species abundance
      existed among and within communities. Significant shifts in plant trait-species
      abundance relationships in a range of environmental properties suggest strong
      environmental filtering processes that influence species abundance and rarity in
      the studied subtropical forests.

PMID- 23560116
TI  - [Osteoid osteoma of the left talus in children].

PMID- 23560115
TI  - Microarray analysis of novel candidate genes responsible for glucose-stimulated
      insulin secretion in mouse pancreatic beta cell line MIN6.
AB  - Elucidating the regulation of glucose-stimulated insulin secretion (GSIS) in
      pancreatic islet beta cells is important for understanding and treating diabetes.
      MIN6 cells, a transformed beta-cell line derived from a mouse insulinoma, retain
      GSIS and are a popular in vitro model for insulin secretion. However, in long
      term culture, MIN6 cells' GSIS capacity is lost. We previously isolated a
      subclone, MIN6 clone 4, from the parental MIN6 cells, that shows well-regulated
      insulin secretion in response to glucose, glybenclamide, and KCl, even after
      prolonged culture. To investigate the molecular mechanisms responsible for
      preserving GSIS in this subclone, we compared four groups of MIN6 cells: Pr-LP
      (parental MIN6, low passage number), Pr-HP (parental MIN6, high passage number),
      C4-LP (MIN6 clone 4, low passage number), and C4-HP (MIN6 clone 4, high passage
      number). Based on their capacity for GSIS, we designated the Pr-LP, C4-LP, and C4
      HP cells as "responder cells." In a DNA microarray analysis, we identified a
      group of genes with high expression in responder cells ("responder genes"), but
      extremely low expression in the Pr-HP cells. Another group of genes ("non
      responder genes") was expressed at high levels in the Pr-HP cells, but at
      extremely low levels in the responder cells. Some of the responder genes were
      involved in secretory machinery or glucose metabolism, including Chrebp, Scgn,
      and Syt7. Among the non-responder genes were Car2, Maf, and Gcg, which are not
      normally expressed in islet beta cells. Interestingly, we found a
      disproportionate number of known imprinted genes among the responder genes. Our
      findings suggest that the global expression profiling of GSIS-competent and GSIS
      incompetent MIN6 cells will help delineate the gene regulatory networks for
      insulin secretion.

PMID- 23560117
TI  - Extramedullary plasmocytoma relapsing at differents sites: an unusual
      presentation.
AB  - Extramedullary plasmacytoma (EMP) is an uncommon plasma cell neoplasm results
      from plasma cell proliferation and consists of monoclonal plasmacytic
      infiltration, without bone marrow involvement and any other systemic
      characteristics of multiple myeloma. EMP accounts for 3% of all plasma cell
      neoplasms and approximately 80% to 90% of EMP involve submucosa of the upper
      aerodigestive, while scrotal, dermis and retroperitoneal infiltration are very
      rare. There are no consensus guidelines for treatment, but EMP is highly
      radiosensitive, surgery may be considered for some sites, but 11 at 30% can
      progress in multiple myeloma. We report here an exceptional case of recurrent EMP
      in much localization. It's about a man 72 years old with initially testicular
      plasmocytoma who generalized the plasmacytic infiltration after 16 months in skin
      and progressively in mediastinal and retroperitoneal plasmacytoma, without any
      medullar and bone involvement.

PMID- 23560118
TI  - [Acute appendicitis and simultaneous ectopic pregnancy: about a rare case].

PMID- 23560120
TI  - Unusual case of cavitary lung metastasis from squamous cell carcinoma of the
      uterine cervix.
AB  - Spontaneous excavation of primary lung cancer is common; however cavitation of
      metastatic lung lesions is rare and usually confused with benign lesions. In
      Moroccan context tuberculosis is the first suspected diagnosis of lung
      excavations. We report a rare case of cavitary lung metastasis of a uterine
      cervix cancer, treated initially as tuberculosis. A 40-year old non-smoking woman
      with a known history of squamous cell carcinoma of the uterine cervix since
      August 2005; presented on September 2008 with right chest pain without fever,
      hemoptysis or weight loss. CT scan showed a thin walled cavity. Empirical
      Antibiotic therapy was conducted 15 days with poor outcome. Then antibacillary
      treatment was started with no proof of mycobacterial infection. A month later,
      the patient presented with gynecological bleeding and a pneumothorax.
      Bronchoscopy with transbronchial biopsy of the cavitary mass was performed.
      Pathology demonstrated a metastatic squamous cell carcinoma. Pelvic examination
      and MRI showed a subsequent local cervix recurrence. Patient underwent 3 courses
      of systemic chemotherapy. She died on June 2009 due to progressive disease. Even
      cavitary lung metastases are rare and benign differential diagnosis are more
      common, clinician should be careful in neoplastic context and investigation
      should be done to eliminate a recurrence.

PMID- 23560119
TI  - An alarming but self-limited case of isolated large spontaneous liver hematoma in
      pregnancy.
AB  - Spontaneous subcapsular liver hematoma is rare but potentially life-threatening
      complication of pregnancy usually associated with severe preeclampsia and HELLP
      syndrome (hemolysis, elevated liver enzymes, and low platelets). We present here
      a case of such a large spontaneous liver hematoma presenting in pregnancy, but
      without other known associated abnormalities, which has not been described before
      and it resolved on itself without any intervention.

PMID- 23560121
TI  - Co-amoxiclav-induced Stevens Johnson syndrome in a child.
AB  - Stevens-Johnson syndrome is an uncommon life threatening disease generally
      induced by drugs. Antibiotics, mainly sulphonamides, are the most involved drugs
      in Stevens-Johnson syndrome in children. Co-amoxiclav is a well tolerated
      antibiotic. It has never been reported to cause, lonely this syndrome in
      children. Herein, we report a co-amoxiclav-induced Stevens-Johnson syndrome
      occurring in an 18-month-old child. The diagnosis of SJS is often challenging in
      children and other possible diseases should be ruled out. The etiology of this
      syndrome is not yet fully understood. It is thought to be mediated by an
      immunologic mechanism. Management involves early identification, withdrawal of
      the culprit drug and rapid initiation of supportive therapies.

PMID- 23560122
TI  - Microalbuminuria in patients with chronic kidney disease at Parirenyatwa Hospital
      in Zimbabwe.

PMID- 23560123
TI  - [Prevalence of HBsAg and anti-HCV antibodies in homozygous sickle cell patients
      at Yaounde Central Hospital].

PMID- 23560124
TI  - [Surgical treatment of malunion of the two bones of the forearm: about a series
      of 11 cases].

PMID- 23560125
TI  - Household costs of seeking outpatient care in Egyptian children with diarrhea: a
      cross-sectional study.
AB  - INTRODUCTION: Addressing difficulties of seeking and getting health care would
      lower the burden of diarrhea among ill children from developing countries as
      Egypt. The purpose of the study is to evaluate the economic burden of diarrhea
      associated with outpatient visits of children in Egypt by identifying the
      different types of related costs. METHODS: This cross-sectional clinic-based
      survey was done by interviewing parents of 763 children presenting with diarrhea
      to the outpatient clinics of Pediatric Hospital of Cairo University. Estimated
      costs included tangible costs (direct, indirect) and intangible costs (forms of
      suffering). Insurance status of the children was also described. Descriptive
      statistics were presented in frequency tables, median, minimum, maximum,
      interquartile range, mean and standard deviation, whenever appropriate. RESULTS:
      It was found that 90.7% of the studied children were of low and middle
      socioeconomic standard with a median monthly family income of US$83 and a median
      monthly expenditure of LE US$79. The average direct and indirect costs of acute
      diarrhea per case were US$13.2+/-19.5 and US$11.3+/-93.1 respectively. The mean
      cost per diarrheal episode is US$24.5 which almost consumes 29.5% of the mean
      monthly income. About 61% of cases sought medical care before visiting our
      hospital, 43.6% of them visited more than one provider. Awareness about health
      insurance was found in 72.7% and coverage by a health insurance system in 33%. Of
      insured patients only 41.4% utilized the insurance services. CONCLUSION: Diarrhea
      causes great socio-economic burden for families in Egypt, which could result in
      significant delay in seeking health care.

PMID- 23560126
TI  - [Localized radiation-induced bullous pemphigoid].

PMID- 23560128
TI  - [Pseudo-keloid lesion revealing a cutaneous and pulmonary sarcoidosis].

PMID- 23560127
TI  - Hepatitis C virus (HCV) infection in Africa: a review.
AB  - Hepatitis C virus (HCV) is a viral pandemic and a leading cause of chronic liver
      disease. This review highlights the epidemiology and management of Hepatitis C in
      Africa. We searched for articles on medline using the terms, "Hepatitis C",
      "Prevalence", "Epidemiology", "Africa" and "Treatment". The bibliographies of the
      articles found were used to find other references. We included articles published
      after 1995 only. The data was summarized and presented in tables and figures.
      Africa has the highest WHO estimated regional HCV prevalence (5.3%). Egypt has
      the highest prevalence (17.5%) of HCV in the world. Genotypes commonly found in
      Africa are 1, 4 and 5. Genotype 3 is found in Egypt and parts of Central Africa.
      Blood transfusion is a major means of acquisition of HCV infection. While
      treatment with peginterferon and ribavirin is recommended for patients with
      chronic HCV, no data were found on their use in Africa. Neither were there any
      data on definitive management (liver transplantation) for those with end stage
      disease. Data on HCV infection in Africa are scarce. This suggests that hepatitis
      C is still a neglected disease in many countries. Limited data exist in
      literature on HCV in Africa.

PMID- 23560129
TI  - Erosive nappy erythema following sunitinib intake.

PMID- 23560130
TI  - [Folie a Trois in Lubumbashi: about one case].

PMID- 23560131
TI  - [Adherence to hypertension and its determinants in the cardiology department of
      the University Hospital of Lome Tokoin].

PMID- 23560132
TI  - Using women advocacy groups to enhance knowledge and home management of febrile
      convulsion amongst mothers in a rural community of Sokoto State, Nigeria.
AB  - INTRODUCTION: Febrile convulsions (FC) are a common paediatric problem worldwide.
      Between 1 and 4% of children will have a febrile convulsion with about 4% of
      cases arising before the age of six months. Although FC is benign and does not
      cause death, brain damage or learning disorders, it is quite frightening to
      observers and parents who witness an episode of FC, would think the child is
      going to die. METHODS: This was a quasi-experimental study (a pre and post-test
      interventional, one group), aimed at assessing the impact of health education on
      knowledge and home management of febrile convulsion amongst mothers in a rural
      community in North Western Nigeria. A one in three samples of fifty mothers that
      met the eligibility criteria where selected using systematic random sampling.
      Structured interviewer administered questionnaire with close and open-ended
      questions was administered to obtain data at pre- and post intervention. RESULTS:
      The ages of the mothers ranged from 18-47 with a mean age of 33 +/- 7.14 years.
      The perceived causes of febrile convulsion included fever (28%), witch craft
      (80%) with majority (98%) of the mothers administering traditional medications.
      Proportion of study subjects with adequate knowledge of febrile convulsion at
      baseline and post intervention were 4% (mean knowledge score of 35.3 +/- 9.48)
      and 96.0% (mean knowledge score of 77.69 +/- 10.75) respectively (P < 0.0001).
      CONCLUSION: Although inadequate knowledge and inappropriate home practices about
      FC were rampant in the study community, using community members to teach and
      sensitize the mothers on FC improved their knowledge base significantly. The use
      of effective educational intervention programmes and parental support groups will
      go a long way in reducing the incidence of FC among children in our communities.

PMID- 23560133
TI  - Impact of home-based management of malaria combined with other community-based
      interventions: what do we learn from Rwanda?
AB  - INTRODUCTION: This study aimed to evaluate the impact of home-based management of
      malaria (HBM) strategy on time to treatment and reported presumed malaria
      morbidity in children aged less than 5 years in Rwanda. METHODS: The study was
      carried out in two malaria-endemic rural districts, one where HBM was applied and
      the other serving as control. In each district, a sample of mothers was surveyed
      by questionnaire before (2004) and after (2007) implementation of HBM. RESULTS:
      After implementation, we observed: i) an increase (P < 0.001) in the number of
      febrile children treated within 24 hours of symptom onset in the experimental
      district (53.7% in 2007 vs 5% in 2004) compared with the control district (28% vs
      7.7%); ii) a decrease in the reported number of febrile children in the
      experimental district (28.7% vs 44.9%, P < 0.01) compared with the control
      district (45.7% vs 56.5%, P < 0.05). CONCLUSION: HBM contributed to decrease time
      to treatment and reported presumed malaria morbidity.

PMID- 23560134
TI  - Religious Engagement in a Risky Family Model Predicting Health in Older Black and
      White Seventh-day Adventists.
AB  - In a structural equation model, associations among latent variables - Child
      Poverty, Risky Family exposure, Religious Engagement, Negative Social
      Interactions, Negative Emotionality, and Perceived Physical Health - were
      evaluated in 6,753 Black and White adults aged 35-106 years (M = 60.5, SD =
      13.0). All participants were members of the Seventh-day Adventist church surveyed
      in the Biopsychosocial Religion and Health Study (BRHS). Child Poverty was
      positively associated with both Risky Family exposure (conflict, neglect, abuse)
      and Religious Engagement (intrinsic religiosity, religious coping,
      religiousness). Risky Family was negatively associated with Religious Engagement
      and positively associated with both Negative Social Interactions (intrusive,
      failed to help, insensitive, rejecting) and Negative Emotionality (depression,
      negative affect, neuroticism). Religious Engagement was negatively associated
      with Negative Emotionality and Negative Social Interactions at a given level of
      risky family. Negative Social Interactions was positively associated with
      Negative Emotionality, which had a direct, negative effect on Perceived Physical
      Health. All constructs had indirect effects on Perceived Physical Health through
      Negative Emotionality. The effects of a risky family environment appear to be
      enduring, negatively affecting one's adult religious life, emotionality, social
      interactions, and perceived health. Religious engagement, however, may counteract
      the damaging effects of early life stress.

PMID- 23560136
TI  - Is increased aortic stiffness associated with advanced ischemic stroke?

PMID- 23560135
TI  - Tricuspid regurgitation: clinical importance and its optimal surgical timing.
AB  - Tricuspid regurgitation (TR) has long been neglected based on the false belief
      that it is substantially rare in prevalence and is not so important in
      determining prognosis. Recent consecutive publications refuted this concept
      surrounding TR, and now we are contemplating this entity from different point of
      view. In this review, we mainly focus on isolated form of severe TR. In our daily
      clinical practice, however, patients with problems in more than one valve are
      more frequently encountered. Hence, we briefly touch on the results of severe TR
      surgery with or without left side valve operations here and there, as well.

PMID- 23560137
TI  - Differences of aortic stiffness and aortic intima-media thickness according to
      the type of initial presentation in patients with ischemic stroke.
AB  - BACKGROUND: Aortic stiffness and intima-media thickness (IMT) are known to be
      associated with ischemic stroke. The aim of the present study was to investigate
      the differences of aortic stiffness and IMT between cerebral infarction (CI) and
      transient ischemic attack (TIA). METHODS: A total of 500 patients with acute
      stroke were divided into 2 groups: the TIA group (n = 230, 62.4 +/- 12 years, 144
      males) versus CI group (n = 270, 63.4 +/- 11 years, 181 males). Aortic stiffness
      index and IMT, as well as conventional cardiovascular risk factors, were
      compared. RESULTS: The prevalence of hypertension, diabetes, and dyslipidemia
      were significantly higher, and left atrial volume and E/E' were significantly
      elevated in the CI group than in the TIA group. Carotid IMT was significantly
      thicker in the CI group than in the TIA group. Aortic stiffness index beta was
      significantly higher (7.99 +/- 2.70 vs. 7.02 +/- 4.30, p = 0.043) and aortic IMT
      was significantly thicker (1.53 +/- 0.41 vs. 1.45 +/- 0.39 mm, p = 0.040) in the
      CI group than in the TIA group. Aortic stiffness index beta was significantly
      correlated with the IMT of the aorta (r = 0.279, p = 0.014), right (r = 412, p <
      0.001) and left carotid artery (r = 441, p < 0.001). CONCLUSION: Aortic stiffness
      index beta and IMT were significantly higher in patients with CI than TIA. The
      result of the present study suggested that CI is associated with more advanced
      degree of atherosclerotic and arteriosclerotic process than TIA.

PMID- 23560138
TI  - The Comparison between the Echocardiographic Data to the Cardiac Catheterization
      Data on the Diagnosis, Treatment, and Follow-Up in Patients Diagnosed as
      Pulmonary Valve Stenosis.
AB  - BACKGROUND: Isolated pulmonary valve stenosis (PS) makes up 6-9% of all
      congenital heart defects among children. The initial gold standard for diagnosis,
      follow-up of PS is by echocardiography. However, the most accurate diagnosis
      still remains to be measurement of the pressure gradient through
      transcatheterization. The purpose of this study is to compare the difference
      between the echocardiographic data to the cardiac catheterization data on the
      diagnosis, treatment, and follow-up in patients diagnosed as PS, and to see what
      parameters should be closely monitored. METHODS: A total of 112 patients (Male :
      Female = 46 : 66) who underwent balloon pulmonary valvuloplasty (BPV) at
      Severance Cardiovascular Hospital, between December, 2002 to August, 2012 were
      retrospectively analyzed. The patients were all under 16 years of age and
      critical PS patients who underwent BPV were excluded from this study. RESULTS:
      The pre-BPV right ventricle (RV)-pulmonary artery (PA) systolic pressure gradient
      and post-BPV systolic pressure gradient showed statistically significant
      decrease. The pre-BPV RV-PA systolic pressure gradient and 3 month post-BPV
      systolic pressure gradient showed statistically significant decrease. The
      consistency between the echocardiographic data and cardiac catheterization data
      shows statistically significant consistency. The mean pressure gradient and
      systolic pressure gradient on the echocardiography shows high consistency when
      comparing with the cardiac catheterization data. CONCLUSION: Our study shows that
      BPV in PS is a safe and effective procedure in children and adolescent. The
      standard echocardiographic evaluation of PS, during diagnosis and follow-up,
      should include mean transpulmonic pressure gradient, as well as the peak systolic
      pressure gradient. The success of the procedure should be held off until at least
      3 months, only if the patients do not show any symptoms.

PMID- 23560139
TI  - Ruptured right sinus of valsalva aneurysm to the right atrium mimicking acute
      myocardial infarction.
AB  - We present a rare case involving a ruptured sinus of Valsalva aneurysm (SVA) and
      acute myocardial infarction in a 39-year-old male patient. Coronary angiography
      showed normal findings; however, the patient showed remarkably elevated levels of
      cardiac enzymes and decreased left ventricular function with apical akinesia on
      transthoracic echocardiography. Transesophageal echocardiography revealed shunt
      flow from the SVA to the right atrium without significant aortic regurgitation.
      Preoperative cardiac arrest was managed by cardiopulmonary resuscitation, and
      surgical repair was performed by closing the entrance of the aneurysm. However,
      the compromised hemodynamic status was not reversed by surgery.

PMID- 23560140
TI  - Fabry cardiomyopathy.
AB  - Fabry disease is a progressive X-linked disorder of glycosphingolipid metabolism
      caused by a deficiency of the alpha-galactosidase lysosomal enzyme. The partial
      or complete deficiency of the lysosomal enzyme leads to an accumulation of
      neutral glycosphingolipids in the vascular endothelium and visceral tissues
      throughout the body. In the heart, glycosphingolipids deposition causes
      progressive left ventricular hypertrophy (LVH). We report a case of Fabry disease
      which was suspected based upon two-dimensional echocardiographic finding of LVH.
      A 44-year-old man was admitted to evaluation of aggravated exertional dyspnea of
      two weeks duration. He had been diagnosed with end-stage renal disease of unknown
      etiology at age 41 followed by renal transplantation that year. He had been
      treated with oral immunosuppressive agents. On hospital day two, transthoracic
      echocardiography revealed concentric LVH. Left ventricular systolic function was
      preserved but diastolic dysfunction was present. Fabry disease was confirmed by
      demonstration of a low plasma alpha-galactosidase A (alpha-Gal A) activity.
      Analysis of genomic DNA showed alpha-Gal A gene mutation. The patient was
      diagnosed with Fabry disease.

PMID- 23560141
TI  - A Case of Kommerell's Diverticulum Initially Detected by Transesophageal
      Echocardiography.
AB  - Kommerell's diverticulum is a rare congenital disorder characterized by typical
      right sided aortic arch and aberrant left subclavian artery which are usually
      detected by accident in asymptomatic patients. However, some of patients complain
      of severe symptoms caused by compression of the adjacent organs or complicated
      aortic dissection by the diverticulum. Early detection of the disease can lead to
      elective surgical correction. In this article, we report a Kommerell's
      diverticulum case initially detected by transesophageal echocardiography.

PMID- 23560142
TI  - Transcatheter treatment of patent foramen ovale combined with abnormal drainage
      of left superior vena cava to left upper pulmonary vein.
AB  - Patent foramen ovale (PFO) has been known to be the cause of transient ischemic
      attacks or stroke, and transcatheter device closure has been the treatment of
      choice for these defects. Combined defect of abnormal drainage of left superior
      vena cava (LSVC) to left superior pulmonary vein (LSPV) in PFO patients is an
      uncommon combination, and both can act as a pathway for paradoxical embolism. We
      report a successful closure of PFO, using Amplatzer(r) PFO occluder (St. Jude
      Medical, St. Paul, MN, USA) and persistent LSVC connected to LSPV using an
      Amplatzer(r) Vascular Plug II (St. Jude Medical, St. Paul, MN, USA). Because this
      combined anomaly of PFO and persistent LSVC can be treated by a single
      transcatheter intervention, if clinically suspected, a complete evaluation for
      this anomaly should be considered.

PMID- 23560143
TI  - Successful embolectomy of a migrated thrombolytic free-floating massive thrombus
      resulting in a pulmonary thromboembolism.
AB  - The optimal treatment for free-floating massive right heart thrombi remains
      uncertain. However, they appear to increase the risk of mortality compared to the
      existence of a solitary pulmonary thromboembolism. Thrombolytic therapy has been
      shown to be effective in most patients, resulting in complete resolution of the
      massive thrombus and clinical improvement. We report the echocardiographic
      disappearance of a free-floating right heart thrombus after thrombolysis,
      however, the thrombus migrated and resulted in pulmonary thromboembolism. It was
      successfully removed with surgery.

PMID- 23560144
TI  - Black defects in severe spontaneous echo contrast teach us the protective aspect
      of mitral regurgitation visually.

PMID- 23560145
TI  - Bubbles in a row: finding of pulmonary arteriovenous fistula on transesophageal
      echocardiography.

PMID- 23560147
TI  - Advances in endoscopic ultrasound-guided biliary drainage: a comprehensive
      review.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has become the first-line
      therapy for bile duct drainage. In the hands of experienced endoscopists,
      conventional ERCP results in a failed cannulation rate of 3% to 5%. This failure
      can occur more commonly in the setting of altered anatomy or technically
      difficult cases due to either duodenal or biliary obstruction. In cases of ERCP
      failure, patients have traditionally been referred for either percutaneous
      transhepatic biliary drainage (PTBD) or surgery. However, both PTBD and surgery
      have higher than desirable complication rates. Within the last decade, endoscopic
      ultrasound-guided biliary drainage (EUS-BD) has become an attractive alternative
      to PTBD after failed ERCP. Many groups have reported on the feasibility, efficacy
      and safety of this technique. This article reviews the indications for ERCP and
      the currently practiced EUS-BD techniques, including EUS-guided rendezvous, EUS
      guided choledochoduodenostomy and EUS-guided hepaticogastrostomy.

PMID- 23560149
TI  - Rescue Endoscopic Ultrasound (EUS)-Guided Trucut Biopsy Following Suboptimal EUS
      Guided Fine Needle Aspiration for Mediastinal Lesions.
AB  - BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)
      and Trucut biopsy (TCB) are sensitive techniques for diagnosing mediastinal
      lesions, but it is unclear how either one or both should be used to obtain a
      pathologic diagnosis. The objective of our study was to evaluate whether EUS-TCB
      impacts the diagnosis of mediastinal lesions after the initial on-site review of
      EUS-FNA specimen suggests a suboptimal result. METHODS: We enrolled consecutive
      patients with mediastinal lesions who underwent EUS-TCB during the same procedure
      if the initial EUS-FNA demonstrated an inadequate FNA sample or suggested that
      histopathology was required for diagnosis. Diagnostic accuracies between
      procedures were compared as the main outcome. RESULTS: Twenty-seven patients (14
      men; median age, 56 years; range, 19 to 82 years) underwent EUS-FNA and EUS-TCB
      to evaluate a mediastinal lymphadenopathy or mass (n=17), to determine the cancer
      stage (n=3) or to exclude tumor recurrence or metastasis (n=7). The overall
      diagnostic accuracies of EUS-FNA and EUS-TCB were 78% and 67%, respectively
      (p=0.375). The combined diagnostic accuracy of EUS-FNA plus EUS-TCB was 82%. In
      six patients with nondiagnostic EUS-FNA, EUS-TCB provided a final diagnosis in
      one patient (17%). CONCLUSIONS: In the current series of patients with
      mediastinal masses or adenopathy, the administration of EUS-TCB following
      suboptimal results for the on-site cytology review did not increase the
      diagnostic yield.

PMID- 23560150
TI  - Effect of biofeedback therapy in constipation according to rectal sensation.
AB  - BACKGROUND/AIMS: The pathophysiologic mechanism of rectal hyposensitivity (RH) is
      not well documented, and the significance of RH in biofeedback therapy (BFT) has
      not been evaluated. Thus, we aimed to assess the effect of BFT in constipated
      patients according to the presence of RH. METHODS: Five hundred and ninety
      constipated patients (238 males and 352 females) underwent anorectal physiologic
      assessments. Of these, anorectal manometry was performed before and after BFT in
      244 patients (63 RH and 181 non-RH patients). RESULTS: The success rate of BFT
      was 56% in the RH and 61% in the non-RH group (p=0.604). The measurements of
      resting pressure, squeezing pressure, desire to defecate volume, urge to defecate
      volume, and maximum volume were decreased after BFT in the RH group (p<0.05),
      whereas only resting and squeezing pressures were decreased in the non-RH group
      (p<0.05). Among the RH group, individuals who responded to BFT showed decreased
      resting pressure, squeezing pressure, desire to defecate, urge to defecate, and
      maximum volume and increased balloon expulsion rate; among those who did not
      respond to BFT, only desire to defecate volume was improved. CONCLUSIONS: In
      constipated patients with RH, changes of anorectal manometric findings differed
      in comparison to patients without RH. The responses to BFT showed both anorectal
      muscle relaxation and restoration of rectal sensation.

PMID- 23560148
TI  - Chemoprevention of gastrointestinal cancer: the reality and the dream.
AB  - Despite substantial progress in screening, early diagnosis, and the development
      of noninvasive technology, gastrointestinal (GI) cancer remains a major cause of
      cancer-associated mortality. Chemoprevention is thought to be a realistic
      approach for reducing the global burden of GI cancer, and efforts have been made
      to search for chemopreventive agents that suppress acid reflux, GI inflammation
      and the eradication of Helicobacter pylori. Thus, proton pump inhibitors,
      statins, monoclonal antibodies targeting tumor necrosis factor-alpha, and
      nonsteroidal anti-inflammatory agents have been investigated for their potential
      to prevent GI cancer. Besides the development of these synthetic agents, a wide
      variety of the natural products present in a plant-based diet, which are commonly
      called phytoceuticals, have also sparked hope for the chemoprevention of GI
      cancer. To perform successful searches of chemopreventive agents for GI cancer,
      it is of the utmost importance to understand the factors contributing to GI
      carcinogenesis. Emerging evidence has highlighted the role of chronic
      inflammation in inducing genomic instability and telomere shortening and
      affecting polyamine metabolism and DNA repair, which may help in the search for
      new chemopreventive agents for GI cancer.

PMID- 23560151
TI  - Miniprobe endoscopic ultrasonography has limitations in determining the T stage
      in early colorectal cancer.
AB  - BACKGROUND/AIMS: Mini-probe endoscopic ultrasonography (mEUS) is a useful
      diagnostic tool for accurate assessment of tumor invasion. The aim of this study
      was to estimate the accuracy of mEUS in patients with early colorectal cancer
      (ECC). METHODS: Ninety lesions of ECC underwent mEUS for pre-treatment staging.
      We divided the lesions into either the mucosal group or the submucosal group
      according to the mEUS findings. The histological results of the specimens were
      compared with the mEUS findings. RESULTS: The overall accuracy for assessing the
      depth of tumor invasion (T stage) was 84.4% (76/90). The accuracy of mEUS was
      significantly lower for submucosal lesions compared to mucosal lesions (p=0.003)
      and it was lower for large tumors (>=2 cm) (p=0.034). The odds ratios of large
      tumors and submucosal tumors affecting the accuracy of T staging were 3.46 (95%
      confidence interval [CI], 1.05 to 11.39) and 6.25 (95% CI, 1.85 to 25.14),
      respectively. When submucosal tumors were combined with large size, the odds
      ratio was 14.67 (95% CI, 1.46 to 146.96). CONCLUSIONS: The overall accuracy of T
      stage determination with mEUS was considerably high in patients with ECC;
      however, the accuracy decreased when tumor size was >2 cm or the tumor had
      invaded the submucosal layer.

PMID- 23560152
TI  - Asymptomatic brain lesions on cranial magnetic resonance imaging in inflammatory
      bowel disease.
AB  - BACKGROUND/AIMS: This study aimed to examine the frequency and type of
      asymptomatic neurological involvement in inflammatory bowel disease (IBD) using
      cranial magnetic resonance imaging (MRI). METHODS: Fifty-one IBD patients with no
      known neurological diseases or symptoms and 30 controls with unspecified
      headaches without neurological origins were included. Patients and controls
      underwent cranial MRI assessments for white matter lesions, sinusitis, otitis
      mastoiditis, and other brain parenchymal findings. RESULTS: The frequencies of
      white matter lesions, other brainstem parenchymal lesions, and otitis-mastoiditis
      were similar in IBD patients and controls (p>0.05), whereas sinusitis was
      significantly more frequent in IBD patients (56.9% vs 33.3%, p=0.041). However,
      among those subjects with white matter lesions, the number of such lesions was
      significantly higher in IBD patients compared to controls (12.75+/-9.78 vs 3.20+/
      2.90, p<0.05). The incidence of examined pathologies did not differ significantly
      with disease activity (p>0.05 for all). CONCLUSIONS: The incidence of white
      matter lesions seemed to be similar in IBD patients and normal healthy
      individuals, and the lesions detected did not pose any clinical significance.
      However, long-term clinical follow-up of the lesions is warranted.

PMID- 23560153
TI  - High Recurrence Rate of Idiopathic Peptic Ulcers in Long-Term Follow-up.
AB  - BACKGROUND/AIMS: Our aim was to compare the long-term clinical outcomes of
      idiopathic peptic ulcer disease (IPUD) with those of Helicobacter pylori-positive
      and nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease
      (PUD). METHODS: Patients with endoscopically diagnosed PUD were retrospectively
      reviewed. According to their H. pylori-infection status and history of NSAIDs
      use, patients were categorized into three groups: H. pylori-positive PUD, NSAID
      induced PUD, and IPUD. Clinical outcomes were analyzed, and the recurrence rate
      of PUD was compared among the three groups. RESULTS: A total of 238 patients were
      enrolled. Those with IPUD, NSAID-induced PUD, and H. pylori-positive PUD
      comprised of 56, 60, and 122 patients, respectively. The 5-year cumulative
      incidences of recurrent ulcers were 24.3% (95% confidence interval [CI], 11.6% to
      37.0%) in IPUD, 10.9% (95% CI, 2.6% to 19.2%) in NSAID-induced PUD, and 3.8% (95%
      CI, 0.1% to 7.5%) in H. pylori-positive PUD (IPUD vs NSAID-induced PUD/H. pylori
      positive PUD, p=0.43/p<0.001 by log-rank test). In the Cox-proportional hazards
      model, only IPUD remained as an independent risk factor associated with recurrent
      ulcers (hazard ratio, 5.97; 95% CI, 1.94 to 18.34; p=0.002). CONCLUSIONS: IPUD
      exhibited a higher recurrence rate than H. pylori-positive and NSAID-induced PUD
      in long-term follow-up and was an independent risk factor for ulcer recurrence.

PMID- 23560154
TI  - Cost Effectiveness Associated with Helicobacter pylori Screening and Eradication
      in Patients Taking Nonsteroidal Anti-Inflammatory Drugs and/or Aspirin.
AB  - BACKGROUND/AIMS: This study was performed to investigate the cost effectiveness
      of Helicobacter pylori screening/eradication in South Korean patients treated
      with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. METHODS: A
      decision Markov model was used to estimate the effectiveness and economic impact
      of an H. pylori screening/eradication strategy compared to a no-screening
      strategy among patients who were included in the model at the age of 40 years.
      Utility weights were applied to four of the health status groups to reflect
      quality-adjusted life years (QALY). The costs of screening, H. pylori
      eradication, and managing peptic ulcer and ulcer complications were obtained from
      South Korea-specific data. RESULTS: The total costs per patient were US $2,454
      for the H. pylori screening/eradication and US $3,182 for the no-screening
      strategy. The QALYs for the two strategies were 16.05 and 15.73, respectively.
      The results were robust for the analyses of all different cohort groups who
      entered the model at the age of 30, 50, or 60 years and for NSAIDs-naive
      patients. Through the probabilistic sensitivity analysis, the robustness of our
      study's results was also determined. CONCLUSIONS: The H. pylori
      screening/eradication strategy was found to be less expensive and more effective
      compared to the no-screening strategy among South Korean patients taking NSAIDs
      and/or aspirin.

PMID- 23560155
TI  - Effect of acute stress on immune cell counts and the expression of tight junction
      proteins in the duodenal mucosa of rats.
AB  - BACKGROUND/AIMS: Duodenal immune alterations have been reported in a subset of
      patients with functional dyspepsia (FD). The aim of this study was to investigate
      the effect of acute stress on immune cell counts and the expression of tight
      junction proteins in the duodenal mucosa. METHODS: Twenty-one male rats were
      divided into the following three experimental groups: 1) the nonstressed, control
      group, 2) the 2-hour-stressed group, and 3) the 4-hour-stressed group.
      Eosinophils, mast cells and CD4(+) and CD8(+) T lymphocytes in the duodenal
      mucosa were counted. The protein and mRNA expressions of occludin and zonula
      occludens-1 (ZO-1) were examined. RESULTS: Eosinophils, mast cells and CD8(+) T
      lymphocyte counts did not differ between the stressed and control groups. The
      number of CD4(+) T lymphocytes and the protein and mRNA expressions of occludin
      and ZO-1 were significantly lower in the 4-hour-stressed group compared with the
      control group. The plasma adrenocorticotrophic hormone and cortisol levels of the
      4-hour-stressed group were significantly higher than those of the control group.
      CONCLUSIONS: Acute stress reduces the number of CD4(+) T lymphocytes and the
      expression of tight junction proteins in the duodenal mucosa, which might be
      associated with the duodenal immune alterations found in a subset of FD patients.

PMID- 23560156
TI  - The Efficacy and Safety of Peginterferon-alpha-2a in Korean Patients with Chronic
      Hepatitis B: A Multicenter Study Conducted in a Real Clinical Setting.
AB  - BACKGROUND/AIMS: Genotype C is the principal type of hepatitis B virus (HBV) in
      Koreans and is associated with poor prognosis for peginterferon alpha-2a therapy.
      The efficacy of and compliance to peginterferon alpha-2a therapy were
      investigated in Koreans with hepatitis B in a real clinical setting. METHODS:
      Hepatitis B patients treated with peginterferon alpha-2a from 2008 to 2011 at
      four university hospitals were consecutively enrolled. RESULTS: Eighty-eight
      patients were enrolled; 67 were hepatitis B e antigen (HBeAg)-positive. The mean
      treatment period was 36.1+/-15.2 weeks. In 26.1% of patients, treatment was
      discontinued due to insufficient antiviral effects and adverse events. At 24
      weeks after treatment, 10/42 (23.8%) HBeAg-positive patients achieved both HBV
      DNA suppression to <2,000 IU/mL and HBeAg loss/seroconversion. For HBeAg-negative
      patients, 10/13 (76.9%) achieved HBV DNA suppression to <2,000 IU/mL at 24 weeks
      after treatment. During the follow-up period, 15 (30.6%) of the 49 patients who
      achieved HBV DNA suppression to 2,000 IU/mL developed a breakthrough HBV DNA
      level of >2*10(6) IU/mL. CONCLUSIONS: Peginterferon alpha-2a therapy in Koreans
      with hepatitis B in a real clinical setting resulted in a lower virologic
      response, as compared to Western individuals, but a favorable durability. There
      is a need to reduce the high rate of premature discontinuation compared to the
      controlled studies.

PMID- 23560157
TI  - Metadherin is a prognostic predictor of hepatocellular carcinoma after curative
      hepatectomy.
AB  - BACKGROUND/AIMS: The prognosis after surgical resection of hepatocellular
      carcinoma (HCC) remains poor because of a high rate of recurrence. Thus, it is
      crucial to identify patients with a high risk of recurrence after curative
      hepatectomy and to develop more effective and targeted treatment strategies to
      improve disease outcomes. In this study, we investigated the roles of metadherin
      (MTDH) in the prognosis of HCC. METHODS: We investigated MTDH expression using
      immunohistochemistry in tumor tissue microarrays of 288 primary HCC patients who
      underwent curative surgical resection. RESULTS: High MTDH expression was observed
      in 138 of the 288 HCC cases (47.9%). High MTDH expression was associated with a
      younger age (p<0.001), higher Edmondson grade (p<0.001), microvascular invasion
      (p<0.001), higher American Joint Committee on Cancer T stage (p=0.001), and
      higher alpha-fetoprotein level (p=0.003). Multivariate analyses revealed that
      high MTDH expression (p=0.014), higher Barcelona-Clinic Liver Cancer (BCLC) stage
      (p<0.001), and Edmondson grade III (p=0.042) were independent predictors of
      shorter disease-free survival (DFS). Higher BCLC stage (p<0.001) and Edmondson
      grade III (p=0.047) were also independent predictors of shorter disease-specific
      survival. CONCLUSIONS: High MTDH expression may be a prognostic predictor of
      shorter DFS in HCC patients after curative hepatectomy.

PMID- 23560158
TI  - A Disintegrin and Metalloprotease with Thrombospondin Motif 2 May Contribute to
      Cirrhosis in Humans through the Transforming Growth Factor-beta/SMAD Pathway.
AB  - BACKGROUND/AIMS: We aimed to investigate the correlation between a disintegrin
      and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming
      growth factor-beta1 (TGF-beta1) in clinical human cirrhotic tissues. METHODS: The
      liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the
      cirrhosis group and eight cases with healthy livers as the normal group) were
      collected. Immunohistochemistry and Western blots were performed to evaluate the
      protein expression levels of ADAMTS-2 and TGF-beta1. Western blots for other key
      mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-beta receptor II
      (TGFbetaRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix
      metalloproteinases 2 (TIMP2), were also performed. RESULTS: Cirrhotic tissues
      showed higher percentages of collagen. The protein expression levels of ADAMTS-2
      and TGF-beta1 were significantly higher in the cirrhotic group as compared to the
      matched normal group (p<0.05), and there was a positive correlation between these
      two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and
      TGFbetaRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were
      significant higher in the cirrhotic group (p<0.01 or p<0.05). CONCLUSIONS: These
      findings suggested that ADAMTS-2 and TGF-beta1 may play important roles in the
      pathogenesis of human cirrhosis; specifically, TGF-beta1 may induce the
      expression of ADAMTS-2 through the TGFbeta/SMAD pathway.

PMID- 23560159
TI  - Lipoic Acid prevents the changes of intracellular lipid partitioning by free
      Fatty Acid.
AB  - BACKGROUND/AIMS: It is suggested that the hepatic lipid composition is more
      important than lipid quantity in the pathogenesis of non-alcoholic
      steatohepatitis. We examined whether lipoic acid (LA) could alter intrahepatic
      lipid composition and free cholesterol distribution. METHODS: HepG2 cells were
      cultured with palmitic acid (PA) with and without LA. Apoptosis, changes of the
      mitochondrial structure, intracellular lipid partitioning, and reactive oxygen
      species (ROS) activity were measured. RESULTS: Free fatty acid (FA) increased
      apoptosis, and LA co-treatment prevented this lipotoxicity (apoptosis in controls
      vs PA vs PA+LA, 0.5% vs 19.5% vs 1.6%, p<0.05). LA also restored the
      intracellular mitochondrial DNA copy number (553+/-33.8 copies vs 291+/-14.55
      copies vs 421+/-21.05 copies, p<0.05) and reversed the morphological changes
      induced by PA. In addition, ROS was increased in response to PA and was decreased
      in response to LA co-treatment (41,382 relative fluorescence unit [RFU] vs 43,646
      RFU vs 41,935 RFU, p<0.05). LA co-treatment increased the monounsaturated and
      polyunsaturated FA concentrations and decreased the total saturated FA fraction.
      It also prevented the movement of intracellular free cholesterol from the cell
      membrane to the cytoplasm. CONCLUSIONS: LA opposes free FA-generated lipotoxicity
      by altering the intracellular lipid composition and free cholesterol
      distribution.

PMID- 23560160
TI  - Risk factors of post endoscopic retrograde cholangiopancreatography bacteremia.
AB  - BACKGROUND/AIMS: Bacteremia following endoscopic retrograde
      cholangiopancreatography (ERCP) is a severe complication, but the risk factors
      for this condition have not yet been clearly determined. Thus, the aim of this
      study was to investigate the risk factors of post-ERCP bacteremia. METHODS: Among
      patients who underwent ERCP from June 2006 to May 2009, we selected patients
      without any signs of infection prior to the ERCP procedures. Of these patients,
      we further selected those who experienced bacteremia after ERCP as well as two
      fold age and sex-matched controls who did not experience bacteremia after ERCP
      procedures. We compared clinical, laboratory and technical aspects between these
      two groups. RESULTS: There were 70 patients (3.1%) who developed bacteremia after
      ERCP. In the multivariate analysis, a history of previous liver transplantation,
      an elevated serum alkaline phosphatase level and an endoscopic retrograde biliary
      drainage procedure were independent risk factors of post-ERCP bacteremia
      (p=0.006, p=0.001, and p=0.004, respectively). The microbiologic analysis
      revealed the presence of gram-negative organisms in 80% of the cases, and 11
      patients had infections with bacteria expressing extended spectrum beta
      lactamases. Pseudomonas infection was significantly more common in patients who
      received liver transplantation as compared to patients without transplantation
      (p=0.014). CONCLUSIONS: A history of liver transplantation, elevated serum
      alkaline phosphatase levels and endoscopic retrograde biliary drainage procedure
      were independent risk factors of post-ERCP bacteremia and require additional
      attention in future studies.

PMID- 23560161
TI  - Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar
      cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Few studies have differentiated immunoglobulin G (IgG) 4-related
      sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we
      sought to investigate useful features for differentiating IgG4-SC from hilar CC.
      METHODS: We retrospectively compared clinical, serological, imaging, and
      histological features of six patients with IgG4-SC and 42 patients with hilar CC.
      RESULTS: In patients with hilar CC, obstructive jaundice was more frequent
      (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum
      CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic
      monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in
      patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were
      significantly higher and frequently elevated. The pancreas was enlarged in all
      IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or
      lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01).
      Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was
      completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct
      stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC
      patients (p<0.01). Bile duct wall thickening in areas without stenosis was more
      frequent in IgG4-SC patients (p<0.01). CONCLUSIONS: An integrated diagnostic
      approach based on clinical, serological, imaging, and histological findings is
      necessary to differentiate IgG4-SC from hilar CC.

PMID- 23560162
TI  - Endoscopic papillectomy for benign ampullary neoplasms: how can treatment outcome
      be predicted?
AB  - BACKGROUND/AIMS: Endoscopic papillectomy is increasingly performed with curative
      intent for benign papillary tumors. This study was performed to identify factors
      that predict the presence of malignancy and affect endoscopic success. METHODS:
      We retrospectively analyzed the medical records of patients who received an
      endoscopic papillectomy for papillary adenoma from 2006 to 2009. RESULTS: A total
      of 43 patients received endoscopic papillectomy. The pathologic results after
      papillectomy revealed adenocarcinoma in five patients (12%), and the risk of
      malignancy was high in cases of large lesions, preprocedural pathology of high
      grade dysplasia or high serum alkaline phosphatase. Endoscopic success was
      observed in 37 patients (86%) at the end of follow-up (mean duration, 10.4+/-9.6
      months). The factor significantly affecting success was a complete resection at
      the initial papillectomy (p=0.007). Two patients experienced recurrence 10 and 32
      months after the complete resection, but both achieved endoscopic success with
      repeated endoscopic treatment. Six patients with endoscopic failure received
      surgical resection. CONCLUSIONS: Endoscopic papillectomy is a safe and effective
      method for the curative resection of benign papillary tumors, especially when
      complete resection is achieved at the initial papillectomy. Follow-up with
      surveillance should be performed for at least 3 years because of the possible
      recurrence of tumors during these periods.

PMID- 23560163
TI  - Transcatheter arterial chemotherapy with miriplatin for hepatocellular carcinoma
      patients with chronic renal failure: report of three cases.
AB  - Miriplatin is a novel lipophilic platinum complex that was developed to treat
      hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting
      chronic renal failure, little prospective data are available regarding the
      clinical toxicity of chemotherapeutic agents used to treat HCC patients with
      chronic renal failure. In a phase II study, the plasma concentration of total
      platinum in patients who received miriplatin was very low, and no severe renal
      toxicity caused by miriplatin injection was reported. Here, we present three
      cases of HCC with stage 4 chronic renal failure who received transcatheter
      arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83
      years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively.
      Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min,
      respectively. All cases were treated for unresectable HCC with transcatheter
      arterial chemotherapy with miriplatin. No serious adverse events were observed,
      and serum creatinine levels did not elevate, even in the patient who experienced
      renal failure caused by cisplatin administration. These results might suggest
      that transcatheter arterial chemotherapy with miriplatin can be safely used in
      HCC patients with chronic renal failure.

PMID- 23560164
TI  - Crohn's Disease Initially Accompanied by Deep Vein Thrombosis and Ulnar
      Neuropathy without Metronidazole Exposure.
AB  - Extraintestinal manifestations are not uncommon in Crohn's disease, and a
      thromboembolic event is a disastrous potential complication. Deep vein thrombosis
      is the most common manifestation of a thromboembolic event and typically occurs
      in association with active inflammatory disease. Peripheral neuropathy in Crohn's
      disease has rarely been reported and is considered an adverse effect of
      metronidazole therapy. Here, we describe a patient who was initially diagnosed
      with Crohn's disease complicated with deep vein thrombosis and ulnar neuropathy
      without metronidazole exposure. The simultaneous occurrence of these
      complications in the early stage of Crohn's disease has never been reported in
      the English literature.

PMID- 23560165
TI  - Percutaneous transhepatic biliary drainage using a ligated catheter for recurrent
      catheter obstruction: antireflux technique.
AB  - Percutaneous transhepatic biliary drainage (PTBD) is an established procedure for
      biliary obstruction. However, duodenobiliary or jejunobiliary reflux of the
      intestinal contents through a PTBD catheter sometimes causes recurrent catheter
      obstruction or cholangitis. A 64-year-old female patient with a history of
      choledochojejunostomy was referred to our department with acute cholangitis due
      to choledochojejunal anastomotic obstruction. Emergent PTBD was performed, but
      frequent obstructions of the catheter due to the reflux of intestinal contents
      complicated the post-PTBD course. We therefore introduced a catheter with an
      antireflux mechanism to prevent jejunobiliary reflux. A commercially available
      catheter was modified; side holes were made at 1 cm and 5 to 10 cm (1 cm apart)
      from the tip of the catheter, and the catheter was ligated with a nylon thread
      just proximal to the first side hole. Using this novel "antireflux PTBD
      technique," jejunobiliary reflux was prevented successfully, resulting in a
      longer patency of the catheter.

PMID- 23560166
TI  - Magnifying endoscopy for intestinal follicular lymphoma is helpful for prompt
      diagnosis.
AB  - The representative endoscopic features of primary intestinal follicular lymphoma
      are well known as small whitish polypoid nodules, but a magnified view has only
      been described in a few case reports. Herein, we report a case with intestinal
      follicular lymphoma in which magnifying endoscopy with narrow band imaging was
      helpful for prompt diagnosis. A 57-year-old Japanese woman underwent surveillance
      esophagogastroduodenoscopy. The endoscopic examination revealed confluent whitish
      granules in the duodenum, distinct from the nodules or polyps that are typical
      findings of intestinal follicular lymphoma. Magnifying endoscopy visualized
      whitish enlarged villi, and narrow band imaging emphasized an elongated and
      coiled vascular pattern. Based on these features, intestinal follicular lymphoma
      was highly suspected, and subsequent histological study confirmed the diagnosis.
      This case demonstrates that magnifying endoscopy with narrow band imaging was
      useful for the detection and prompt diagnosis of intestinal follicular lymphoma.
      The pathological features of intestinal follicular lymphoma are also discussed.

PMID- 23560167
TI  - Comparative Visualization of Ensembles Using Ensemble Surface Slicing.
AB  - By definition, an ensemble is a set of surfaces or volumes derived from a series
      of simulations or experiments. Sometimes the series is run with different initial
      conditions for one parameter to determine parameter sensitivity. The
      understanding and identification of visual similarities and differences among the
      shapes of members of an ensemble is an acute and growing challenge for
      researchers across the physical sciences. More specifically, the task of gaining
      spatial understanding and identifying similarities and differences between
      multiple complex geometric data sets simultaneously has proved challenging. This
      paper proposes a comparison and visualization technique to support the visual
      study of parameter sensitivity. We present a novel single-image view and sampling
      technique which we call Ensemble Surface Slicing (ESS). ESS produces a single
      image that is useful for determining differences and similarities between
      surfaces simultaneously from several data sets. We demonstrate the usefulness of
      ESS on two real-world data sets from our collaborators.

PMID- 23560168
TI  - Rat peripheral nerve regeneration using nerve guidance channel by porcine small
      intestinal submucosa.
AB  - OBJECTIVE: In order to develop a novel nerve guidance channel using porcine small
      intestinal submucosa (SIS) for nerve regeneration, we investigated the
      possibility of SIS, a tissue consisting of acellular collagen material without
      cellular immunogenicity, and containing many kinds of growth factors, as a
      natural material with a new bioactive functionality. METHODS: Left sciatic nerves
      were cut 5 mm in length, in 14 Sprague-Dawley rats. Grafts between the cut nerve
      ends were performed with a silicone tube (Silicon group, n=7) and rolled porcine
      SIS (SIS group, n=7). All rats underwent a motor function test and an
      electromyography (EMG) study on 4 and 10 weeks after grafting. After last EMG
      studies, the grafts, including proximal and distal nerve segments, were retrieved
      for histological analysis. RESULTS: Foot ulcers, due to hypesthesia, were fewer
      in SIS group than in Silicon group. The run time tests for motor function study
      were 2.67 seconds in Silicon group and 5.92 seconds in SIS group. Rats in SIS
      group showed a better EMG response for distal motor latency and amplitude than in
      Silicon group. Histologically, all grafts contained some axons and myelination.
      However, the number of axons and the degree of myelination were significantly
      higher in SIS group than Silicon group. CONCLUSION: These results show that the
      porcine SIS was an excellent option as a natural biomaterial for peripheral nerve
      regeneration since this material contains many kinds of nerve growth factors.
      Furthermore, it could be used as a biocompatible barrier covering neural tissue.

PMID- 23560169
TI  - Dysregulated Expression Profiles of MicroRNAs of Experimentally Induced Cerebral
      Aneurysms in Rats.
AB  - OBJECTIVE: Cerebral aneurysm (CA) is an important acquired cerebrovascular
      disease that can cause catastrophic results. MicroRNAs (miRNAs) are small non
      coding RNAs, playing essential roles in modulating basic physiologic and
      pathological processes. Currently, evidences have been established about biologic
      relationship between miRNAs and abdominal aortic aneurysms. However, biologic
      roles of miRNAs in CA formation have not been explained yet. We employed
      microarray analysis to detect and compare miRNA expression profiles in late stage
      of CA in rat model. METHODS: Twenty-six, 7-week-old male Sprague-Dawley rats
      underwent a CA induction procedure. The control animals (n=11) were fed a normal
      diet, and the experimental animals (n=26) were fed a normal diet with 1% normal
      saline for 3 months. Then, the rats were sacrificed, their cerebral arteries were
      dissected, and the five regions of aneurysmal dilation on the left posterior
      communicating artery were cut for miRNA microarrays analysis. Six miRNAs (miRNA
      1, miRNA-223, miRNA-24-1-5p, miRNA-551b, miRNA-433, and miRNA-489) were randomly
      chosen for validation using real-time quantitative PCR. RESULTS: Among a set of
      differentially expressed miRNAs, 14 miRNAs were over-expressed more than 200% and
      6 miRNAs were down-expressed lower than 50% in the CA tissues. CONCLUSION: The
      results show that miRNAs might take part in CA formation probably by affecting
      multiple target genes and signaling pathways. Further investigations to identify
      the exact roles of these miRNAs in CA formation are required.

PMID- 23560170
TI  - Critical use of balloon angioplasty after recanalization failure with retrievable
      stent in acute cerebral artery occlusion.
AB  - OBJECTIVE: Sudden major cerebral artery occlusion often resists recanalization
      with currently available techniques or can results in massive symptomatic
      intracranial hemorrhage (sICH) after thrombolytic therapy. The purpose of this
      study was to examine mechanical recanalization with a retrievable self-expanding
      stent and balloon in acute intracranial artery occlusions. METHODS: Twenty-eight
      consecutive patients with acute intracranial artery occlusions were treated with
      a Solitaire retrievable stent. Balloon angioplasty was added if successful
      recanalization was not achieved after stent retrieval. The angiographic outcome
      was assessed by Thrombolysis in Cerebral Infarction (TICI) and the clinical
      outcomes were assessed by the National Institutes of Health Stroke Scale (NIHSS)
      and the modified Rankin Scale (mRS). RESULTS: At baseline, mean age was 69.4
      years and mean initial NIHSS score was 12.5. A recanalization to TICI 2 or 3 was
      achieved in 24 patients (85%) after stent retrieval. Successful recanalization
      was achieved after additional balloon angioplasty in 4 patients. At 90-day follow
      up, 24 patients (85%) had a NIHSS improvement of >=4 and 17 patients (60%) had a
      good outcome (mRS <=2). Although there was sICH, there was one death associated
      with the procedure. CONCLUSION: Mechanical thromboembolectomy with a retrievable
      stent followed by additional balloon angioplasty is a safe and effective first
      line therapy for acute intracranial artery occlusions especially in case of
      unsuccessful recanalization after stent thrombectomy.

PMID- 23560171
TI  - Combined open door laminoplasty with unilateral screw fixation for unstable multi
      level cervical stenosis : a preliminary report.
AB  - OBJECTIVE: The authors reviewed their experiences of combined surgery (open door
      laminoplasty with unilateral screw fixation) for unstable multi-level cervical
      stenosis, to clarify the situation regarding the surgical approach most
      appropriate for the treatment of diffuse unstable multi-level cervical stenosis.
      METHODS: From January 2011 to January 2012, combined surgery was performed for
      unstable multi-level cervical stenosis by one surgeon at our institution. The
      subjects of this study were 6 men of mean age 53.7 years (range, 48-71) with a
      mean follow-up of 9.3 (range, 3-14) months. All imaging studies showed severe
      multi-level cervical stenosis with spinal cord signal change, and instability or
      kyphotic deformity. A retrospective review of clinical, radiological, and
      surgical data was conducted. RESULTS: Average laminoplasty level was 4.8 and the
      average screw fixation level was 5.0. Japanese Orthopedic Association score
      improved from an average of 5.2 to 11.2 points. According to Nurick's grades and
      Odom's criteria, symptom improvement was statistically significant. On the other
      hand, Cobb's angle changes were not significant. Average operation time was 5.86
      hours with an average blood loss of 460 mL. No significant surgical complication
      was encountered. CONCLUSION: Despite the small cohort and the short follow-up
      duration, the present study demonstrates that laminoplasty with unilateral screw
      fixation is a safe and effective treatment for unstable multi-level cervical
      stenosis.

PMID- 23560172
TI  - Prevalence of disc degeneration in asymptomatic korean subjects. Part 2 :
      cervical spine.
AB  - OBJECTIVE: Similar to back pain, neck pain has recently shown to have increasing
      prevalence. Magnetic resonance imaging (MRI) is useful in identifying the causes
      of neck pain. However, MRI shows not only pathological lesions but also
      physiological changes at the same time, and there are few Korean data. The
      authors have attempted to analyze the prevalence of disc degeneration in highly
      selective asymptomatic Korean subjects using MRI. METHODS: We performed 3 T MRI
      sagittal scans from C2 to T1 on 102 asymptomatic subjects (50 men and 52 women)
      who visited our hospital between the ages of 14 and 82 years (mean age 46.3
      years). All images were read independently by three observers (two neurosurgeons
      and one neuroradiologist) who were not given any information about the subjects.
      We classified grading for cervical disc herniation (HN), annular fissure (AF),
      and nucleus degeneration (ND), using disc degeneration classification. RESULTS:
      The prevalence of HN, AF, and ND were 81.0%, 85.9%, and 95.4%, respectively. High
      prevalence of HN, AF, and ND was shown compared to previous literature.
      CONCLUSION: In asymptomatic Korean subjects, the abnormal findings of 3 T MRI
      showed a high prevalence in HN, AF, and ND. Several factors might play important
      roles in these results, such as population-specific characters, MRI field
      strength, and disc degeneration grading system.

PMID- 23560173
TI  - Difference of Sagittal Spinopelvic Alignments between Degenerative
      Spondylolisthesis and Isthmic Spondylolisthesis.
AB  - OBJECTIVE: The purpose of this study was to analyze the differences of
      spinopelvic parameters between degenerative spondylolisthesis (DSPL) and isthmic
      spondylolisthesis (ISPL) patients. METHODS: Thirty-four patients with DSPL and 19
      patients with ISPL were included in this study. Spinopelvic parameters were
      evaluated on whole spine X-rays in a standing position. The following spinopelvic
      parameters were measured : pelvic incidence (PI), sacral slope, pelvic tilt (PT),
      lumbar lordosis (LL), and sagittal vertical axis from C7 plumb line (SVA). The
      population of patients was compared with a control population of 30 normal and
      asymptomatic adults. RESULTS: There were statistically significant differences in
      LL (p=0.004) and SVA (p=0.005) between the DSPL and ISPL group. The LL of DSPL
      (42+/-13 degrees ) was significantly lower than that of the control group (48+/
      11 degrees ; p=0.029), but that of ISPL (55+/-6 degrees ) was significantly
      greater than a control group (p=0.004). The SVA of DSPL (55+/-49 mm) was greater
      than that of a control group (<40 mm), but that of ISPL (21+/-22 mm) was within
      40 mm as that of a control group. The PT of DSPL (24+/-7 degrees ) and ISPL (21+/
      7 degrees ) was significantly greater than that of a control group (11+/-6
      degrees ; p=0.000). CONCLUSION: Both symptomatic DSPL and ISPL patients had a
      greater PI than that of the asymptomatic control group. In conclusion, DSPL
      populations are likely to have global sagittal imbalance (high SVA) compared with
      ISPL populations because of the difference of lumbar lordosis between two groups.

PMID- 23560174
TI  - Clinical application of gamma knife dose verification method in multiple brain
      tumors : modified variable ellipsoid modeling technique.
AB  - OBJECTIVE: The Leksell Gamma Knife(r) (LGK) is based on a single-fraction high
      dose treatment strategy. Therefore, independent verification of the Leksell
      GammaPlan(r) (LGP) is important for ensuring patient safety and minimizing the
      risk of treatment errors. Although several verification techniques have been
      previously developed and reported, no method has ever been tested statistically
      on multiple LGK target treatments. The purpose of this study was to perform and
      to evaluate the accuracy of a verification method (modified variable ellipsoid
      modeling technique, MVEMT) for multiple target treatments. METHODS: A total of
      500 locations in 10 consecutive patients with multiple brain tumor targets were
      included in this study. We compared the data from an LGP planning system and
      MVEMT in terms of dose at random points, maximal dose points, and target volumes.
      All data was analyzed by t-test and the Bland-Altman plot, which are statistical
      methods used to compare two different measurement techniques. RESULTS: No
      statistical difference in dose at the 500 random points was observed between LGP
      and MVEMT. Differences in maximal dose ranged from -2.4% to 6.1%. An average
      distance of 1.6 mm between the maximal dose points was observed when comparing
      the two methods. CONCLUSION: Statistical analyses demonstrated that MVEMT was in
      excellent agreement with LGP when planning for radiosurgery involving multiple
      target treatments. MVEMT is a useful, independent tool for planning multiple
      target treatment that provides statistically identical data to that produced by
      LGP. Findings from the present study indicate that MVEMT can be used as a
      reference dose verification system for multiple tumors.

PMID- 23560175
TI  - Intracerebral hemorrhage following evacuation of a chronic subdural hematoma.
AB  - Burr hole drainage has been widely used to treat chronic subdural hematomas
      (SDH), and most of them are easily treated by simple trephination and drainage.
      However, various complications, such as, hematoma recurrence, infection, seizure,
      cerebral edema, tension pneumocephalus and failure of the brain to expand due to
      cerebro-cranial disproportion may develop after chronic SDH drainage. Among them,
      intracerebral hemorrhage after evacuation of a recurrent chronic SDH is very
      rare. Here, we report a fatal case of delayed intracerebral hemorrhage caused by
      coagulopathy following evacuation of a chronic SDH. Possible pathogenic
      mechanisms of this unfavorable complication are discussed and a review of
      pertinent literature is included.

PMID- 23560176
TI  - Slowly recovering isolated bilateral abducens nerve palsy after embolization of
      ruptured anterior communicating artery aneurysm.
AB  - Bilateral abducens nerve palsy related to ruptured aneurysm of the anterior
      communicating artery (ACoA) has only been reported in four patients. Three cases
      were treated by surgical clipping. No report has described the clinical course of
      the isolated bilateral abducens nerve palsy following ruptured ACoA aneurysm
      obliterated with coil. A 32-year-old man was transferred to our institution after
      three days of diplopia, dizziness and headache after the onset of a 5-minute
      generalized tonic-clonic seizure. Computed tomographic angiography revealed an
      aneurysm of the ACoA. Magnetic resonance imaging showed focal intraventricular
      hemorrhage without brain stem abnormalities including infarction or space
      occupying lesion. Endovascular coil embolization was conducted to obliterate an
      aneurysmal sac followed by lumbar cerebrospinal fluid (CSF) drainage. Bilateral
      paresis of abducens nerve completely recovered 9 weeks after ictus. In
      conclusion, isolated bilateral abducens nerve palsy associated with ruptured ACoA
      aneurysm may be resolved successfully by coil embolization and lumbar CSF
      drainage without directly relieving cerebrospinal fluid pressure by opening
      Lillequist's membrane and prepontine cistern.

PMID- 23560177
TI  - Spontaneous anterior cerebral artery dissection presenting with simultaneous
      subarachnoid hemorrhage and cerebral infarction in a patient with multiple
      extracranial arterial dissections.
AB  - Simultaneous subarachnoid hemorrhage and infarction is a quite rare presentation
      in a patient with a spontaneous dissecting aneurysm of the anterior cerebral
      artery. Identifying relevant radiographic features and serial angiographic
      surveillance as well as mode of clinical manifestation, either hemorrhage or
      infarction, could sufficiently determine appropriate treatment. Enlargement of
      ruptured aneurysm and progressing arterial stenosis around the aneurysm indicates
      impending risk of subsequent stroke. In this setting, prompt treatment with stent
      assisted endovascular embolization can be a reliable alternative to direct
      surgery. When multiple arterial dissections are coexistent, management strategy
      often became complicated. However, satisfactory clinical results can be obtained
      by acknowledging responsible arterial site with careful radiographic inspection
      and antiplatelet medication.

PMID- 23560178
TI  - Remote cerebellar hemorrhage after intradural disc surgery.
AB  - We report a rare case of remote cerebellar hemorrhage after intradural disc
      surgery at the L1-2 level. Two days after the spine surgery, patient complained
      unexpected headache, dizziness, nausea and vomiting. From the urgently conducted
      brain CT, it was reported that the patient had cerebellar hemorrhage. Occipital
      craniotomy and hematoma evacuation was performed, and hemorrhagic lesion on the
      right cerebellum was effectively removed. After occipital craniotomy, the patient
      showed signs of improvement on headache, dizziness, nausea and vomiting. He was
      able to leave the hospital after two weeks of initial operation without any
      neurological deficit. Remote cerebellar hemorrhage following spinal surgery is
      extremely rare, but may occur from dural damage of spinal surgery, accompanied
      with cerebrospinal fluid leakage. Early diagnosis is particularly important for
      the optimal treatment of remote cerebellar hemorrhage.

PMID- 23560179
TI  - Granular cell tumor of the intradural extramedullary spinal cord : report of two
      cases with respect to radiological differential diagnosis.
AB  - Granular cell tumors (GrCTs) of the spinal cord are rare benign tumors with a
      high rate of local recurrence. Only 6 cases of spinal GrCTs have been reported.
      GrCT is difficult to distinguish from other benign tumors such as schwannoma
      using imaging. A radiological "speckled dots" sign may be a useful
      differentiating feature of GrCT based upon experience with two cases and a review
      of the literature.

PMID- 23560180
TI  - Cervical spinal epidural hematoma following cervical posterior
      laminoforaminotomy.
AB  - A 65-year-old man who had lateral cervical disc herniation underwent cervical
      posterior laminoforaminotomy at C5-6 and C6-7 level right side. During the
      operation, there was no serious surgical bleeding event. After operation, he
      complained persistent right shoulder pain and neck pain. Repeated magnetic
      resonance image (MRI) showed diffuse cervical epidural hematoma (EDH) extending
      from C5 to T1 level right side and spinal cord compression at C5-6-7 level. He
      underwent exploration. There was active bleeding at muscular layer. Muscular
      active bleeding was controlled and intramuscular hematoma was removed. The
      patient's symptom was reduced after second operation. Symptomatic postoperative
      spinal EDH requiring reoperation is rare. Meticulous bleeding control is
      important before wound closure. In addition, if patient presents persistent or
      aggravated pain after operation, rapid evaluation using MRI and second look
      operation is needed as soon as possible.

PMID- 23560181
TI  - An unusual cervical spinal meningioma in a child.
AB  - The incidence of spinal meningioma is very rare in children. A 14-year-old girl
      presented with right arm weakness, gait disturbance, and urinary incontinence.
      Cervical magnetic resonance imaging revealed an intradural extramedullary tumor
      dorsal to the spinal cord in the level of C1. The tumor was totally removed
      despite the severe cord compression. Meningotheliomatous meningioma was diagnosed
      after histological examination.

PMID- 23560182
TI  - Usefulness of ultrasound for detecting suspected peripheral nerve lesions in
      diagnosis of peripheral neuropathy : case report and brief review of the
      literature.
AB  - Ultrasound scanning of a peripheral nerve along its expected course is a simple
      and useful method for determining the cause of peripheral neuropathy. We present
      3 cases of peripheral neuropathy in which the pathology was detected by simple
      ultrasound scanning of the affected nerve. There were 2 cases of entrapment
      neuropathy due to mucoid cyst and 1 case of nerve sheath tumor. All lesions were
      visualized by simple ultrasound scanning of the involved peripheral nerve. Our
      results suggest that if a lesion affecting the peripheral nerve is suspected
      after history and physical examination or electrophysiologic studies, ultrasound
      scanning of the peripheral nerve of interest throughout its course is very
      helpful for identifying the causative lesion.

PMID- 23560183
TI  - Percutaneous vertebroplasty for painful spinal metastasis: a good option for
      better quality of life.

PMID- 23560184
TI  - Medical simulation is needed in anesthesia training to achieve patient's safety.
AB  - Many medical schools and hospitals throughout the world are equipped with a
      simulation center for the purpose of training anesthesiologists to perform both
      technical and non-technical skills. Because induction, maintenance, and emergence
      of general anesthesia are critical to patient welfare, various simulation
      mannequins and tools are utilized for the purpose of training anesthesiologists
      for safer patient care. Traditionally, anesthesia residency training mostly
      consisted of didactic lectures and observations. After completion of
      "traditional" training, anesthesia residents were allowed to perform procedures
      on patients under supervision. However, simulation would be a more effective
      training tool for which to teach anesthesiologists the skills necessary to
      perform invasive procedures, such as endotracheal intubation, central venous
      catheter insertion, and epidural catheter insertion. Recently, non-technical
      skills, such as the Anesthesia Non-Technical Skills developed by
      anesthesiologists from Aberdeen University, have been emphasized as an important
      training resource. Technical skills and non-technical skills can be learned by
      anesthesiology residents through a standardized and organized simulation program.
      Such programs would be beneficial in training anesthesia residents to work
      efficiently as a team in the operation room.

PMID- 23560185
TI  - Efficacy of the oral neurokinin-1 receptor antagonist aprepitant administered
      with ondansetron for the prevention of postoperative nausea and vomiting.
AB  - BACKGROUND: 5-HT3 receptor antagonist, dexamethasone and droperidol were used for
      the prevention of postoperative nausea and vomiting (PONV). Recently, neurokinin
      1 (NK1) antagonist has been used for PONV. We evaluated the effect of oral
      aprepitant premedication in addition to ondansetron. METHODS: A total 90 patients
      scheduled for elective rhinolaryngological surgery were allocated to three groups
      (Control, Ap80, Ap125), each of 30 at random. Ondansetron 4 mg was injected
      intravenously to all patients just before the end of surgery. On the morning of
      surgery, 80 mg and 125 mg aprepitant were additionally administered into the Ap80
      group and Ap125 group, respectively. The rhodes index of nausea, vomiting and
      retching (RINVR) was checked at 6 hr and 24 hr after surgery. RESULTS: Twelve
      patients who used steroids unexpectedly were excluded. Finally 78 patients
      (control : Ap80 : Ap125 = 24 : 28 : 26) were enrolled. Overall PONV occurrence
      rate of Ap125 group (1/26, 3.9%) was lower (P = 0.015) than the control group
      (7/24, 29.2%) at 6 hr after surgery. The nausea distress score of Ap125 group
      (0.04 +/- 0.20) was lower (P = 0.032) than the control group (0.67 +/- 1.24) at 6
      hr after surgery. No evident side effect of aprepitant was observed. CONCLUSIONS:
      Oral aprepitant 125 mg can be used as combination therapy for the prevention of
      PONV.

PMID- 23560186
TI  - Tracheal intubation with rocuronium using a "modified timing principle".
AB  - BACKGROUND: Rapid sequence induction (RSI) is indicated in various situations.
      Succinylcholine has been the muscle relaxant of choice for RSI, and rocuronium
      has become an alternative medicine for patients who cannot be administered
      succinylcholine for various reasons. Although rocuronium has the most rapid onset
      time among non-depolarizing muscle relaxants, the standard dose of rocuronium
      (0.6 mg/kg) takes 60 seconds to achieve appropriate muscle relaxation. We
      evaluated intubating conditions using the "modified timing principle" with
      rocuronium and succinylcholine. METHODS: In this prospective controlled blinded
      study, all patients received 1.5 ug/kg fentanyl intravenously with preoxygenation
      for 2 minutes and were randomized to receive 0.6 mg/kg rocuronium followed by 1.5
      mg/kg propofol or 1.5 mg/kg propofol and 1.5 mg/kg succinylcholine. The
      rocuronium group was intubated just after confirming loss of consciousness, and
      the succinylcholine group was intubated 1 minute after injecting succinylcholine.
      Intubation condition, timing of events, and complications were recorded. RESULTS:
      All patients were successfully intubated in both groups. Apnea time of the
      rocuronium group (38.5 seconds) was significantly shorter than that in the
      succinylcholine group (100.7 seconds). No significant differences were observed
      in loss of consciousness time or intubation time. The succinylcholine group
      tended to show better intubation conditions, but no significant difference was
      observed. None of the patients complained awareness of the intubation procedure
      or had respiratory difficulty during a postoperative interview. CONCLUSIONS: The
      modified RSI with rocuronium showed shorter intubation sequence, acceptable
      intubation conditions, and a similar level of complications compared to those of
      conventional RSI with succinylcholine.

PMID- 23560187
TI  - Comparison of recovery profiles of propofol and sevoflurane anesthesia with
      bispectral index monitoring in percutaneous nephrolithotomy.
AB  - BACKGROUND: The aim of the study was to evaluate the comparative effects of
      propofol infusion versus sevoflurane for maintenance of anesthesia with respect
      to hemodynamics, recovery characteristics, nausea and vomiting in patients
      undergoing percutaneous nephrolithotomy. METHODS: Forty American Society of
      Anesthesiologists physical status I-II patients, aged between 22 and 65 years
      were randomly divided to receive either intravenous anesthesia with propofol
      (group P) or sevoflurane (group S). Cardiovascular variables, peripheral oxygen
      saturation (SpO2), end-tidal carbon dioxide (ETCO2), bispectral index (BIS) and
      train-of-four (TOF) values were recorded at intervals throughout the procedure.
      Time to spontaneous respiration, eye opening, extubation, obey commands, hand
      squeezing, Aldrete Score > 9 and the incidence of postoperative nausea and
      vomiting were recorded. RESULTS: Early recovery times [spontaneous respiration (P
      = 0.002), eye opening (P = 0.006), extubation (P = 0.013), obey commands (P <
      0.05), hand squeezing (P = 0.005)] were significantly longer in group P. The
      incidence of vomiting was significantly higher in group S (P < 0.05). Hemodynamic
      parameters, levels of SpO2, ETCO2, and BIS and TOF values were not significantly
      different between the groups (P > 0.05). CONCLUSIONS: The present study which
      adjusted sevoflurane concentration and propofol infusion rate according to BIS
      values revealed that maintenance of anesthesia with sevoflurane is associated
      with faster recovery than anesthesia with propofol. Propofol resulted in a
      significantly lower incidence of postoperative nausea and vomiting. Hemodynamic
      parameters and levels of SpO2 and ETCO2 were comparable between the groups during
      percutaneous nephrolithotomy.

PMID- 23560188
TI  - Comparison of meperidine and nefopam for prevention of shivering during spinal
      anesthesia.
AB  - BACKGROUND: Shivering is a frequent event during spinal anesthesia and meperidine
      is a well-known effective drug for prevention and treatment of shivering. Nefopam
      is a non-opiate analgesic and also known to have an anti-shivering effect. We
      compared nefopam with meperidine for efficacy of prevention of shivering during
      spinal anesthesia. METHODS: Sixty five patients, American Society of
      Anesthesiologists physical status I or II, aged 20-65 years, scheduled for
      elective orthopedic surgery under spinal anesthesia were investigated. Patients
      were randomly divided into two groups, meperidine (Group M, n = 33) and nefopam
      (Group N, n = 32) groups. Group M and N received meperidine 0.4 mg/kg or nefopam
      0.15 mg/kg, respectively, in 100 ml of isotonic saline intravenously. All drugs
      were infused for 15 minutes by a blinded investigator before spinal anesthesia.
      Blood pressures, heart rates, body temperatures and side effects were checked
      before and at 15, 30, and 60 minutes after spinal anesthesia. RESULTS: The
      incidences and scores of shivering were similar between the two groups. The mean
      arterial pressures in Group N were maintained higher than in Group M at 15, 30,
      and 60 minutes after spinal anesthesia. The injection pain was checked in Group N
      only and its incidence was 15.6%. CONCLUSIONS: We conclude that nefopam can be a
      good substitute for meperidine for prevention of shivering during spinal
      anesthesia with more stable hemodynamics, if injection pain is effectively
      controlled.

PMID- 23560189
TI  - Effect of position changes after spinal anesthesia with low-dose bupivacaine in
      elderly patients: sensory block characteristics and hemodynamic changes.
AB  - BACKGROUND: The purpose of this study is to compare the anesthetic
      characteristics in elderly patients who remain in sitting position for 2 min
      compared with patients that are placed in supine position after induction of
      spinal anesthesia. METHODS: Fifty-seven patients scheduled for transurethral
      surgery were randomized to assume supine position immediately after 6.5 mg
      hyperbaric bupivacaine were injected (L group) or to remain in the sitting
      position for 2 minutes before they also assumed the supine position (S group).
      Analgesic levels were assessed bilaterally, using pin-prick. Motor block was
      scored using a 12-point scale. The mean arterial pressure and heart rate were
      also recorded. RESULTS: Sensory block levels were significantly lower at all time
      points for the L group. However, there were no significant differences in the
      degree of the motor block and hemodynamic changes between the two groups.
      However, in the L group, ephedrine or atropine were administered to three
      patients. CONCLUSIONS: We concluded that performing a spinal anesthesia in
      sitting position was technically easier and induced less hypotension.

PMID- 23560190
TI  - Effect of ketorolac on the prevention of emergence agitation in children after
      sevoflurane anesthesia.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of ketorolac on
      the incidence and severity of emergence agitation in children recovering from
      sevoflurane anesthesia. METHODS: Eighty-five children aged 3 to 7 years were
      randomly assigned to the control group or the ketorolac group (1 mg/kg
      ketorolac). The children were evaluated by the Pediatric Anesthesia Emergence
      Delirium Scale and a four-point agitation scale. RESULTS: The median agitation
      scores did not differ significantly between the two groups. The overall incidence
      of emergence agitation was similar in the two groups (41% in the control group
      vs. 32% in the ketorolac group, P = 0.526). The number of children who received
      rescue drugs for treatment of emergence agitation was not significantly different
      between the two groups. CONCLUSIONS: The administration of 1 mg/kg of ketorolac
      is not effective in decreasing the incidence and severity of emergence agitation
      in children aged 3 to 7 years after sevoflurane anesthesia.

PMID- 23560191
TI  - Bispectral index monitoring correlates with the level of consciousness in brain
      injured patients.
AB  - BACKGROUND: In general, measuring the level of consciousness in neurological
      patients is important. To assess the patient's mental status, the Glasgow Coma
      Scale (GCS) and the level of consciousness (drowsiness, stupor, and coma) have
      been used in clinical situations. The aim of the present study was to identify
      the correlation between bispectral index (BIS) and level of consciousness in
      brain injured patients. METHODS: Eighty-nine adult patients of both sexes were
      included in the study. A blinded observer evaluated the mental status (GCS and
      level of consciousness) of a patient who is admitted in intensive care unit with
      brain injury, while an investigator noted the patient's BIS. The BIS was measured
      using a BIS monitor, Model A-3000 vistaTM with Sensor Bis quatroTM (Aspect
      Medical Systems, Norwood, USA). A Spearman's rank correlation coefficient was
      used to determine if the level of consciousness correlated with the BIS. RESULTS:
      In 89 patients, the BIS was found to be significantly correlated with the level
      of consciousness (r = 0.723, P < 0.01) and GCS (r = 0.646, P < 0.01). The BIS
      values increased with an increasing level of consciousness. Mean BIS values of
      coma, semicoma, stupor and drowsiness were 0.14 +/- 0.23, 38.9 +/- 18.0, 60.3 +/-
      14.5, and 73.6 +/- 16.5, respectively. CONCLUSIONS: In the present study, a
      significant correlation existed between level of consciousness and BIS. These
      findings suggest that BIS may be used for assessing the level of consciousness in
      brain injured patients. However, the scatter of BIS values for any level of
      consciousness limited the worth of BIS in predicting mentality except in coma
      patients.

PMID- 23560192
TI  - False selection of syringe-brand compatibility and the method of correction
      during target-controlled infusion of propofol.
AB  - BACKGROUND: We evaluated volumetric differences of syringe brand compatibilities,
      and investigated the impact of false brand settings on target-controlled infusion
      (TCI) and their methods of correction. METHODS: Gravimetric measurement of 10 ml
      bolus infusions was performed using BD Plastipak (BDP) and Terumo compatible
      syringes, while setting to 7 different kinds of brand compatibilities (BDP,
      Sherwood Monoject, BD Perfusion, Braun Perfusor, Braun Omnifix, Fresenius
      Injectomat, and Terumo). To investigate the performance of TCI using BDP with a
      false setting to Terumo (BDPTERUMO) and Terumo to BDP (TERUMOBDP), 24 TCI
      targeting 4.0 ug/ml of effect-site concentration (Ceff) of propofol were
      performed. Subsequently, another 24 TCI were evaluated for simple corrections of
      false settings at 30 min. We also investigated 24 TCI using active corrections
      (fill-up for BDPTERUMO, evacuation for TERUMOBDP) based on the pharmacokinetics
      of propofol. The Ceff at 30 min of TCI and time to normalize to +/- 5% of target
      concentration (T+/-5%target) were compared. RESULTS: The Ceff of BDPTERUMO showed
      negative bias and 17.2% inaccuracy, and the Ceff of TERUMOBDP showed positive
      bias and 19.5% inaccuracy. The Ceff at 30 min showed no difference between the
      methods of correction in BDPTERUMO or TERUMOBDP. The T+/-5%target in both the
      active corrections was significantly shorter than that of each simple corrections
      (P < 0.001). CONCLUSIONS: False brand setting of syringe proportionally
      maintained different predicted concentrations as much as the volumetric
      differences of syringe brand. Based on the results, it is proposed that
      correction methods based on pharmacokinetics could effectively normalize the
      differences, without giving up the wrong TCI.

PMID- 23560193
TI  - Functional activity of the cannabinoid 1 receptor is not affected by opioid
      antagonists in the rat brain.
AB  - BACKGROUND: WIN55212-2 is a synthetic cannabinoid agonist and selective to
      cannabinoid 1 (CB1) receptors, which are distributed mainly in the central
      nervous system. Opioid receptors and CB1 receptors have several similarities in
      terms of their intracellular signal transduction mechanisms, distributions, and
      pharmacological action. Several studies have therefore sought to describe the
      functional interactions between opioids and cannabinoids at the cellular and
      behavioral levels. The present study investigated agonist-stimulated
      [(35)S]GTPgammaS binding by WIN55212-2 in rat brain membranes and determined the
      antagonism by selective opioid antagonists at the level of receptor-ligand
      interaction and intracellular signal transduction. METHODS: Sprague-Dawley rats
      (male, n = 20) were euthanized for the preparation of brain membranes. In agonist
      stimulated [(35)S]GTPgammaS binding by WIN55212-2, the values of EC50 and maximum
      stimulation (% over basal) were determined in the absence or presence of the u,
      kappa and delta opioid receptor antagonists naloxone (20 nM), norbinaltorphimine
      (3 nM), and naltrindole (3 nM), respectively. Ke values for opioid antagonist
      inhibition in the absence or presence of each opioid receptor antagonist were
      calculated using the following equation: [nanomolar antagonist] / (dose ratio of
      EC50 - 1). RESULTS: In WIN55212-2-stimulated [(35)S]GTPgammaS binding in the rat
      brain membranes, the values of EC50 and maximum stimulation (% over basal) were
      154 +/- 39.5 nM and 27.6 +/- 5.3% over basal, respectively. Addition of selective
      opioid antagonists did not produce a significant rightward shift in the WIN55212
      2 concentration-response curve, and Ke values were not applicable. CONCLUSIONS:
      Our results suggest that the functional activity of WIN55212-2-stimulated
      [(35)S]GTPgammaS binding was not affected by opioid antagonists in the rat brain
      membranes. Although the exact mechanism remains unclear, our results may
      partially elucidate their actions.

PMID- 23560194
TI  - Anesthetic management of a patient with Huntington's chorea -A case report-.
AB  - Huntington's chorea is a rare hereditary disorder of the nervous system. It is
      inherited as an autosomal dominant disorder and is characterized by progressive
      chorea, dementia and psychiatric disturbances. The best anesthetic technique is
      yet to be established for these patients with increased risk of aspiration due to
      involvement of pharyngeal muscles and an exaggerated response to sodium
      thiopental and succinylcholine. The primary goal in general anesthesia for these
      patients is to provide airway protection and a rapid and safe recovery. We report
      the anesthetic management of a 51-year-old patient with Huntington's chorea
      admitted for an emergency operation.

PMID- 23560195
TI  - A cardiovascular collapse occurred in the beach chair position for shoulder
      arthroscopy under general anesthesia -A case report-.
AB  - The occurrence of severe hypotension and bradycardia, following placing to the
      beach chair position from supine during general anesthesia for repair of tendon
      injury of the rotator cuff of shoulder in a healthy 50 year-old man was
      described. The Bezold-Jarisch reflex, which is known to inhibit cardiovascular
      reflex and composed of three kinds of symptoms such as vasodilation, bradycardia
      and hypotension, has been reported mainly in peripheral nerve block, and may
      occur during orthostasis, hypovolemia, hemorrhage, supine inferior vena cava
      compression in pregnancy, interscalene block for shoulder surgery in the sitting
      position and so on. The bradycardia and hypotension can be more aggravated when
      causative elements overlaps each other. Anticholinergics and vasopressor were
      injected intravenously, and position of the patient was changed to the supine
      position immediately resulting in a normal vital signs dramatically.

PMID- 23560196
TI  - Anesthetic management for cesarean delivery in a Guillain-Barre syndrome patient 
      A case report-.
AB  - Guillain-Barre syndrome is an acute inflammatory demyelinating polyradiculopathy
      characterized by progressive motor weakness, areflexia, and ascending paralysis.
      Guillain-Barre syndrome is extremely rare in pregnant patients, and there are no
      established guidelines for delivery or safest anesthetic methods. We report a
      Cesarean delivery in the case of a 32-year old woman who was diagnosed with
      Guillain-Barre syndrome 18 weeks into gestation. Tracheostomy was performed due
      to progressive respiratory muscle weakness and respiratory failure, and
      ventilator support was required in the intensive care unit. The respiratory
      difficulty was exacerbated by the growth of the fetus, necessitating emergency
      Cesarean delivery. The delivery was successfully performed under general
      anesthesia, and the patient recovered without neurological sequelae.

PMID- 23560197
TI  - Drug overdose due to malfunction of a patient-controlled analgesia machine -A
      case report-.
AB  - Patient-controlled analgesia (PCA) provides excellent pain control and high
      stability, thereby minimizing the incidence of adverse effects. However, one of
      our patients experienced respiratory depression and hypotension within 30 minutes
      of initiation of PCA therapy. We discovered that machine malfunction caused
      continuous activation of the PCA button, resulting in a drug overdose. The PCA
      machine was sent to the manufacturer, who found an electrical short in the PCA
      button. All PCA units of the same make and model were immediately removed from
      hospitals and replaced with redesigned units without defects in the PCA button.
      We have used the improved machines without any problems. The purpose of this
      report is to raise awareness of this type of malfunction in PCA units in order to
      help prevent adverse events in the future.

PMID- 23560198
TI  - Percutaneous vertebroplasty at C7 for the treatment of painful metastases -A case
      report-.
AB  - The cervical spine is a less common site for metastatic disease than is the
      thoracolumbar spine. Percutaneous vertebroplasty (PVP) in the cervical spine can
      be performed using an anteromedial or lateral approach. A 51-year-old woman with
      breast cancer had been experiencing severe weight-bearing neck pain for 2 months,
      even after undergoing radiation therapy. Imaging studies revealed an osteolytic
      compression fracture in the C7 vertebra. For performing PVP at C7 using the
      anteromedial approach, a needle was inserted from the left side of the patient's
      neck. The needle was advanced to the anterior 1/3 anterior 1/3 or 1/2 of the
      vertebral body by hammering, and approximately 2 ml of cement was injected.
      Immediately after the operation, the patient could move her neck without pain. In
      conclusion, PVP using an anterolateral approach may be an option for treating
      metastatic osteolytic vertebral lesions in the cervical spine for alleviating
      intractable axial neck pain.

PMID- 23560199
TI  - Hemidiaphragmatic paralysis and hemohydrothorax following right internal jugular
      vein catheterization.

PMID- 23560200
TI  - Unanticipated difficult endotracheal intubation due to an undiagnosed pharyngeal
      web.

PMID- 23560201
TI  - Anesthetic considerations in patients with large obstructing vocal process
      granuloma.

PMID- 23560202
TI  - Delayed peripartum cardiomyopathy after emergency cesarean section.

PMID- 23560203
TI  - Extreme thrombocytosis in a traumatic patient.

PMID- 23560204
TI  - Blood pressure management and regional cerebral oxygen saturation during surgery
      in beach chair position.

PMID- 23560205
TI  - The Korea national health and nutrition examination survey as a primary data
      source.

PMID- 23560206
TI  - Effect of Lactobacillus gasseri BNR17 on Overweight and Obese Adults: A
      Randomized, Double-Blind Clinical Trial.
AB  - BACKGROUND: Lactobacillus gasseri BNR17 is a type of probiotic strain isolated
      from human breast milk. A study was reported regarding the fact that BNR17 was an
      inhibitor of obesity and diabetic activities in the human body through previous
      animal experiments. This study was furthered to investigate the effect of BNR17,
      a probiotic strain isolated from human breast milk, on obese and overweight
      adults. METHODS: Sixty-two obese volunteers aged 19 to 60 with body mass index >=
      23 kg/m(2) and fasting blood sugar >= 100 mg/dL participated in a placebo
      controlled, randomized, and double-blind trial. For 12 weeks, 57 participants
      were given either placebo or BNR17 and were tested by measuring body fat, body
      weight, various biochemical parameters, vital signs, and computed tomography at
      the start of the study and at weeks 4, 8, and 12. The subjects assumed usual
      daily activities without having to make behavioral or dietary modifications
      during the course of the study. RESULTS: At the 12th week, a slight reduction in
      body weight was noted in the BNR17 group, but there were no significant weight
      changes between groups. Decrease of waist and hip circumferences in the BNR17
      group was more pronounced than those in the placebo group. The two groups had no
      special or severe adverse reactions. CONCLUSION: Despite there being no change in
      behavior or diet, administration of only the supplement of BNR17 reduced weight
      and waist and hip circumference. However, there were no significant differences
      between the two groups. These findings warrant a subsequent longer-term
      prospective clinical investigation with a large population.

PMID- 23560207
TI  - The effect of videotaping students' interviews with patients for interview skill
      education.
AB  - BACKGROUND: The importance of communication between patients and physicians has
      been proven in many previous studies. The authors analyzed the effect of
      interview skill education through videotapes which recorded students' interviews
      with real patients in the outpatient department of family medicine. METHODS: This
      study was conducted with all students who chose the elective course of family
      medicine and one randomly selected student every week from an 'infectious
      internal medicine' class at Dongguk University Ilsan Hospital during the period
      from December 2008 to March 2011. All students performed a preliminary
      examination of a new patient at the outpatient department of family medicine. All
      consultations were videotaped. Feedback to the student was given on the same day
      by viewing the videotape together. After feedback, all students performed another
      preliminary examination of one new patient at the department of family medicine
      the same week. Three family medicine residents scored all videotapes using 10
      item interview skill checklists. Many parts of the checklists were modified using
      the Arizona Clinical Interview Rating Scales. RESULTS: Thirty-three students
      participated. Of 10 items, nine showed increased scores after feedback. There was
      a significant change in four items after feedback: 'type of question' (before
      2.36 +/- 0.60, after 2.73 +/- 0.72), 'timeline' (before 2.82 +/- 0.68, after 3.18
      +/- 0.73), 'positive verbal reinforcement' (before 2.24 +/- 0.56, after 2.61 +/-
      0.90), and the total score (before 21.70 +/- 2.62, after 23.39 +/- 3.13) (P <
      0.05). CONCLUSION: Giving feedback to medical school students on medical
      interview skills using videotapes of students' preliminary consultations with
      real patients in outpatient settings, was effective in improving the interview
      areas of 'type of question,' 'timeline,' 'positive verbal reinforcement,' and the
      total interview scores.

PMID- 23560208
TI  - Inter-arm Differences in Simultaneous Blood Pressure Measurements in Ambulatory
      Patients without Cardiovascular Diseases.
AB  - BACKGROUND: It has traditionally been known that there is normally a difference
      in blood pressure (BP) between the two arms; there is at least 20 mm Hg
      difference in the systolic blood pressure (SBP) and 10 mm Hg difference in the
      diastolic blood pressure (DBP). However, recent epidemiologic studies have shown
      that there are between-arm differences of < 5 mm Hg in simultaneous BP
      measurements. The purposes of this study is to examine whether there are between
      arm differences in simultaneous BP measurements obtained from ambulatory patients
      without cardiovascular diseases and to identify the factors associated these
      differences. METHODS: We examined 464 patients who visited the outpatient clinic
      of Gangneung Asan Hospital clinical department. For the current analysis, we
      excluded patients with ischemic heart disease, stroke, arrhythmia, congestive
      heart failure, or hyperthyroidism. Simultaneous BP measurements were obtained
      using the Omron MX3 BP monitor in both arms. The inter-arm difference (IAD) in BP
      was expressed as the relative difference (right-arm BP [R] minus left-arm BP [L]:
      R - L) and the absolute difference (|R - L|). RESULTS: The mean absolute IAD in
      SBP and DBP were 3.19 +/- 2.38 and 2.41 +/- 1.59 mm Hg, respectively, in men and
      2.61 +/- 2.18 and 2.25 +/- 2.01 mm Hg, respectively, in women. In men, there were
      83.8% of patients with the IAD in SBP of <= 6 mm Hg, 98.1% with the IAD in SBP of
      <= 10 mm Hg, 96.5% with the IAD in DBP of <= 6 mm Hg and 0% with the IAD in DBP
      of > 10 mm Hg. In women, 89.6% of patients had IAD in SBP of <= 6 mm Hg, 92.1%
      with IAD in DBP of <= 6 mm Hg, and 0% with IAD in SBP of > 10 mm Hg or IAD in DBP
      of > 10 mm Hg. Gangneung Asan Hospital clinical series of patients showed that
      the absolute IAD in SBP had a significant correlation with cardiovascular risk
      factors such as the 10-year Framingham cardiac risk scores and higher BP in men
      and higher BP in women. However, the absolute IAD in SBP and DBP had no
      significant correlation with the age, obesity, smoking, drinking, hyperlipidemia,
      diabetes, metabolic syndrome, and renal function. CONCLUSION: Our results showed
      that there were no significant between-arm differences in simultaneous BP
      measurements. It was also shown that most of the ambulatory patients without
      cardiovascular diseases had an IAD in SBP of < 10 mm Hg and an IAD in DBP of < 6
      mm Hg.

PMID- 23560209
TI  - Factors associated with poor sleep quality in primary care.
AB  - BACKGROUND: Sleep disorder is a common problem in adults and affects physical and
      mental health. We investigated factors associated with poor sleep quality in
      Korean primary care. METHODS: A total of 129 couples (129 husbands and 129 wives)
      aged 30 to 79 years were included in this study from March, 2009 to February,
      2010. The subjects were surveyed using a specific questionnaire. Sleep disorder
      was defined by a Pittsburgh Sleep Quality Index global score greater than 5 (poor
      sleepers). The subjects were divided into a group of good sleepers (n = 160) and
      a group of poor sleepers (n = 98). Socio-demographic and clinical covariates
      including age, sex, depression, spouse sleep disorder, and spouse depression were
      reported. RESULTS: Poor sleep quality was present in 38.0% of total subjects.
      According to chi-square test results, female, patients with depression, and low
      sleep quality of spouse were significantly associated with sleep disorder. In
      multivariate logistic regression analysis, depression increased the risk of poor
      sleep quality (odds ratio [OR], 7.775; 95% confidence interval [CI], 2.555 to
      23.661), and non-risky drinking decreased the risk of poor sleep quality (OR,
      0.343; 95% CI, 0.128 to 0.924). CONCLUSION: In our study, more than one-third of
      participants had poor sleep quality. Depression was a strong independent factor
      associated with sleep problems.

PMID- 23560210
TI  - Associations between the Risk of Internet Addiction and Problem Behaviors among
      Korean Adolescents.
AB  - BACKGROUND: The number of internet users is increasing rapidly and internet
      addiction among adolescents has become a serious public health problem in Korea.
      In the light of behavioral addiction, this study was aimed to identify the
      associations between the risk of internet addiction and other problem behaviors
      which can lead to addiction, such as cigarette smoking, alcohol drinking, drug
      abuse, and sexual intercourse among a nationally representative sample of Korean
      adolescents. METHODS: Data from the 2010 Korean Youth Risk Behavior Web-based
      Survey (respondents, 73,238) were analyzed. Risk of internet addiction was
      assessed by the 'Korean Internet Addiction Proneness Scale for Youth-Short Form:
      Self Report' which was developed by the Korean National Information Society
      Agency in 2008. Multiple logistic regression analysis was used to calculate the
      odds ratios of problem behaviors among adolescents at high risk for internet
      addiction and adolescents at low risk for internet addiction. RESULTS: The odds
      of smoking experience, drug abuse experience, and sexual intercourse experience
      were significantly higher among boys at high risk for internet addiction compared
      to boys at low risk for internet addiction. Among girls at high risk of internet
      addiction, the odds of smoking experience, drinking experience, and drug abuse
      experience were significantly higher compared with girls at low risk of internet
      addiction. CONCLUSION: The risk of internet addiction was associated with
      cigarette smoking, alcohol drinking, drug abuse, and sexual intercourse
      experience among Korean adolescents.

PMID- 23560211
TI  - Relationships between the Level of Alcohol Consumption and Abnormality in
      Biomarkers According to Facial Flushing in Korean Male Drinkers.
AB  - BACKGROUND: This research investigated the association between facial flushing
      after drinking and alcohol-induced biomarker abnormalities. METHODS: This
      retrospective study included 374 male drinkers who visited the department of
      Family Medicine of Chungnam National University Hospital between January and
      December of 2010. The participants were classified into two groups: the flushing
      group (n = 107) and the non-flushing group (n = 267). The biomarkers assessed
      were % carbohydrate-deficient transferrin (CDT) and gamma glutamyl transferase
      (rGTP). The upper limits of %CDT and rGTP were set as 2.47 and 50, respectively.
      The receiver operating characteristic (ROC) curve was used to obtain the cut-off
      value for the amount of drinking that caused abnormal %CDT and rGTP levels in the
      two groups. The sensitivity and specificity of the cut-off drinking amount for
      %CDT and rGTP abnormalities were analyzed in each group. RESULTS: In the flushing
      group, the cut-off value for alcohol-induced %CDT abnormality was 3.38 drinks (1
      drink: 14 g of alcohol) per week, with sensitivity of 77.8% and specificity of
      70.4%. In the non-flushing group, the cut-off value was 11.25 drinks per week,
      with sensitivity of 62.2% and specificity of 69.6%. The cut-off value for the
      amount of alcohol that induced rGTP abnormality was 3.38 drinks per week in the
      flushing group, with sensitivity of 68.0% and specificity of 76.8%, whereas it
      was 8.75 drinks in the non-flushing group, with sensitivity of 71.1% and
      specificity of 66.7%. The area under the ROC of the drinking level was 0.726 in
      the flushing group and 0.684 in the non-flushing group for %CDT. For rGTP, the
      value was 0.738 in the flushing group and 0.718 in the non-flushing group.
      CONCLUSION: The weekly drinking amount required to induce biomarker abnormalities
      was lower in the flushers than in the non-flushers.

PMID- 23560212
TI  - Socioeconomic status in association with metabolic syndrome and coronary heart
      disease risk.
AB  - BACKGROUND: The purpose of this study was to examine the association of metabolic
      syndrome (MS) coronary heart disease (CHD) with socioeconomic status (SES).
      METHODS: The participants were 2,170 (631 men and 1,539 women), aged over 40
      years who had visited for health screening from April to December in 2009. We
      classified them into three SES levels according to their education and income
      levels. MS was defined using the criteria of modified National Cholesterol
      Education Program Adult Treatment Panel III and CHD risk was defined using
      Framingham risk score (FRS) >= 10%. RESULTS: High, middle, and low SES were
      12.0%, 73.7%, and 14.3%, respectively. The prevalence of MS was 18.1%. For high,
      middle, and low SES, after adjusted covariates (age, drinking, smoking, and
      exercise), odds ratios for MS in men were 1.0, 1.41 (confidence interval [CI],
      0.83 to 2.38; P > 0.05), and 1.50 (CI, 0.69 to 3.27; P > 0.05), respectively and
      in women were 1.0, 1.74 (CI, 1.05 to 3.18; P < 0.05), and 2.81 (CI, 1.46 to 2.43;
      P < 0.05), respectively. The prevalence of FRS >= 10% was 33.5% (adjusted
      covariates were drinking, smoking, and exercise) and odds ratios for FRS >= 10%
      in men were 1.0, 2.86 (CI, 1.35 to 6.08; P < 0.001), and 3.12 (CI, 1.94 to 5.00;
      P < 0.001), respectively and in women were 1.0, 3.24 (CI, 1.71 to 6.12; P <
      0.001), and 8.80 (CI, 4.50 to 17.23; P < 0.001), respectively. CONCLUSION: There
      was an inverse relationship between SES and FRS >= 10% risk in men, and an
      inverse relationship between SES and both risk of MS and FRS >= 10% in women.

PMID- 23560213
TI  - Cardiopulmonary fitness is independently associated with insulin resistance in
      non-diabetes mellitus patients of a university hospital in Korea.
AB  - BACKGROUND: Insulin resistance, decreased response of peripheral tissue to normal
      insulin levels, is known to be related to cardiometabolic diseases.
      Cardiopulmonary fitness is also considered to be related to these comorbidities.
      Therefore, we investigated the relationship between insulin resistance and
      cardiopulmonary fitness by performing a 3-minute step test in a Korean non
      diabetes mellitus (DM) population. METHODS: A total of 118 non-DM subjects were
      enrolled during their routine health check-up. Insulin resistance was measured by
      calculating homeostatic model assessment-insulin resistance (HOMA-IR), and a 3
      minute step test was performed to measure cardiopulmonary fitness. RESULTS: Post
      60 seconds exercise heart rate after 3-minute test (R60 heart rate) was
      correlated with age (r = -0.21, P = 0.02), education (r = 0.17, P = 0.04), body
      mass index (r = 0.23, P = 0.01), waist circumference (r = 0.28, P < 0.01),
      fasting insulin (r = 0.28, P < 0.01), HOMA-IR (r = 0.25, P < 0.01), low density
      lipoprotein-cholesterol (r = 0.28, P < 0.01), high sensitivity C-reactive protein
      levels (r = 0.22, P = 0.02), and baseline heart rate (r = 0.56, P < 0.01). In a
      step-wise multiple regression analysis, baseline heart rate (beta = 0.79, P <
      0.001), HOMA-IR (beta = 0.65, P = 0.02), and systolic blood pressure (beta =
      0.15, P = 0.03) were identified as explanatory variables for R60 heart rates.
      CONCLUSION: Our results suggested that cardiopulmonary fitness was associated
      with insulin resistance in non-DM patients of a university hospital in Korea.
      Further studies are needed to elucidate the underlying mechanisms.

PMID- 23560214
TI  - Differences in blood pressure measurements obtained using an automatic
      oscillometric sphygmomanometer depending on clothes-wearing status.
AB  - BACKGROUND: According to the current guidelines for blood pressure monitoring,
      clinicians are recommended to measure blood pressure by completely exposing the
      upper arm. However, it is a common practice that blood pressure is measured with
      the cuff placed over the sleeve or with the sleeve rolled up. We therefore
      conducted this study to examine whether there are any differences in blood
      pressure measurements among the three different settings: the sleeve group, the
      rolled sleeve group, and the bare arm group. METHODS: We conducted the current
      study in 141 male and female adult patients who visited our clinical department.
      In these patients, we took repeatedly blood pressure measurements using the same
      automatic oscillometric device on three different settings. Then, we analyzed the
      results with the use of randomized block design analysis of variance. RESULTS:
      The mean values of systolic blood pressure (SBP) between the first reading and
      those of the second reading were 128.5 +/- 10.6 mm Hg in the sleeve group, 128.3
      +/- 10.8 mm Hg in the rolled sleeve group, and 128.3 +/- 10.7 mm Hg in the bare
      arm group. These results indicate that there were no significant differences
      among the three groups (P = 0.32). In addition, the mean values of diastolic
      blood pressure (DBP) between the first reading and those of the second reading
      were 80.7 +/- 6.1 mm Hg in the sleeve group, 80.7 +/- 6.1 mm Hg in the rolled
      sleeve group, and 80.6 +/- 5.9 mm Hg in the bare arm group. These results
      indicate that there were no significant differences among the three groups (P =
      0.77). In addition, based on the age, sex, past or current history of
      hypertension or diabetes mellitus, the thickness of sleeve, weight, a drinking
      history, and a smoking history, there were no significant differences in SBP and
      DBP among the three groups. CONCLUSION: There were no significant differences in
      blood pressure measurements between the three different settings (the sleeve
      group, the rolled sleeve group, and the bare arm group).

PMID- 23560216
TI  - Comments on statistical issues in march 2013.

PMID- 23560215
TI  - Thoracolumbar Junction Syndrome Causing Pain around Posterior Iliac Crest: A Case
      Report.
AB  - Thoracolumbar junction syndrome is characterized by referred pain which may
      originate at the thoracolumbar junction, which extends from 12th thoracic
      vertebra to 2nd lumbar vertebra, due to functional abnormalities. Clinical
      manifestations include back pain, pseudo-visceral pain and pseudo-pain on the
      posterior iliac crest, as well as irritable bowel symptoms. During clinical
      examination, pain can be demonstrated by applying pressure on the facet joints or
      to the sides of the spinous processes. Radiological studies show only mild and
      insignificant degenerative changes in most cases. We report a 42-year-old female
      patient with osteogenesis imperfecta who suffered from chronic low back pain.
      Under the diagnosis of thoracolumbar junction syndrome, she was treated with an
      epidural block and a sympathetic nerve block, which improved her symptoms.

PMID- 23560217
TI  - Primary adenocarcinoma of the lung with a synchronous carcinoid tumour of the
      small intestine.

PMID- 23560218
TI  - Fit for the future? The place of global health in the UK's postgraduate medical
      training: a review.
AB  - OBJECTIVES: That health is now global is increasingly accepted. However, a
      'mismatch between present professional competencies and the requirements of an
      increasingly interdependent world' has been identified. Postgraduate training
      should take account of the increasingly global nature of health; this paper
      examines the extent to which they currently do. DESIGN: Trainees across 11
      medical specialties reviewed the content of their postgraduate curriculum.
      SETTING: Not relevant. PARTCIPANTS: None. MAIN OUTCOME MEASURES: Competencies
      were coded as 'UK' (statement only relevant to UK work), 'global' (statement with
      an explicit reference to aspects of health outside the UK) or generic (relevant
      both to the UK and international settings). RESULTS: Six of the 11 curricula
      reviewed contained global health competencies. These covered the global burden or
      determinants of disease and appropriate policy responses. Only one College
      required trainees to 'be aware of the World Health Organization', or 'know the
      local, national and international structures for health care'. These cross
      cutting competencies have applicability to all specialties. All 11 curricula
      contained generic competencies where a global health perspective and/or
      experience could be advantageous, e.g. caring for migrant or culturally different
      patients. CONCLUSION: Trainees in all specialties should achieve a minimum
      requirement of global health awareness. This can be achieved through a small
      number of common competencies that are consistent across core curricula. These
      should lead on from equivalent undergraduate competencies. Addressing the current
      gap in the global health content of postgraduate medical curricula will ensure
      that the UK has health professionals that are trained to meet the health
      challenges of the future.

PMID- 23560219
TI  - An old friend revisited: chloramphenicol optic neuropathy.

PMID- 23560220
TI  - 'Initial Clinical Experience' articles are poorly cited and negatively affect the
      impact factor of the publishing journal: a review.
AB  - OBJECTIVES: The phrase 'Initial Clinical Experience' in a manuscript's title
      implies that the described technique offers promise of future clinical relevance.
      We assessed, using rates of subsequent citations, the actual academic relevance
      of such articles in comparison to articles not containing the phrase. DESIGN: We
      searched ISI database for articles that included the studied phrase in their
      titles between 1975 and 2009 and grouped the results by the related medical
      specialty. We excluded articles from journals with no available impact factor.
      For each identified article, we extracted number of included patients,
      citations/year, the average impact factor of the publishing journal over the last
      five years and the proportion of articles published in the same journal that
      garnered zero subsequent citations. SETTING: Retrospective review of a scientific
      database. PARTICIPANTS: None. MAIN OUTCOME MEASURES: Citation rate. RESULTS:
      Among a total of 982,127 articles published in 186 journals representing eight
      major publishing medical specialties, 531 (0.05%) were Initial Clinical
      Experience articles. Thirty percent of Initial Clinical Experience articles were
      never cited compared with 7% of the overall article volume (p < 0.0001).
      Citations/year for Initial Clinical Experience articles were significantly lower
      than the median impact factor (p < 0.0001). There was no correlation between
      citations and number of patients described in the Initial Clinical Experience
      articles (p = 0.61). CONCLUSIONS: Initial Clinical Experience articles are cited
      less frequently than the average, especially in Cardiovascular, Radiology and
      Ophthalmology journals.

PMID- 23560221
TI  - Number needed to sacrifice: statistical taboo or decision-making tool?
AB  - The percentage that benefit from medical preventive measures is small but all are
      exposed to the risk of side effects so most of those harmed would never benefit
      from their use. There is no expression or acronym to describe the ratio of harm
      to benefit nor discussion of what level of harm is acceptable for what benefit.
      Here we describe the harm to benefit ratio (HBR) expressed as number harmed (H)
      for 100 to benefit (B) and calculated for commonly used medical interventions.
      For post TIA carotid endarterectomy the HBR is 25 (25 postoperative strokes or
      deaths are caused for 100 to be stroke free at 5 years); warfarin in atrial
      fibrillation in patients aged under 65 results in 400 intracerebral haemorrhages
      for every 100 saved from a thromboembolic event; fibrinolytic treatment for
      stroke causes 44 symptomatic intracranial haemorrhages for every 100 that have
      minimal disability at 3 months; aspirin in high risk patients causes 33 major
      bleeds for every 100 occlusive vascular events prevented; routine inpatient
      thromboprophylaxis causes 133 additional bleeds for every 100 pulmonary emboli
      prevented; breast cancer screening causes 1000 unnecessary cancer treatments for
      100 cancer deaths to be prevented. CONCLUSION: The HBR or number needed to
      sacrifice is larger than most imagine. Its wider use would allow us better to
      recognise the number harmed, allow better informed consent, compare different
      preventive strategies and understand the risks as well as benefits of preventive
      treatments.

PMID- 23560222
TI  - Pleomorphic adenoma of the accessory parotid gland misdiagnosed as glomus tumour.

PMID- 23560223
TI  - Non-islet cell tumour induced-hypoglycaemia as a cause of delirium.

PMID- 23560224
TI  - Integrating specialist advice following reforms: an interview-based survey.
AB  - OBJECTIVES: To investigate the importance of incorporating secondary care input
      to aid commissioning following National Health Service reforms which will see the
      replacement of Primary Care Trusts with Clinical Commissioning Groups; to
      determine barriers that might arise given that this issue had been raised during
      public consultations and to explore ways to improve this input. DESIGN:
      Qualitative project with semistructured one-to-one interviews which were audio
      recorded, transcribed and analysed using thematic content analysis by two
      investigators. The findings were discussed and organized into a framework.
      SETTING: Bradford and Airedale, UK. PARTICIPANTS: We interviewed 19 participants
      from primary care, the medical directorship and a range of specialties. MAIN
      OUTCOME MEASURES: One-to-one semistructured interviews allowed a flexible
      dialogue to discuss planned questions and any other themes which participants
      brought up. This elicited a variety of experiences and ideas which provided the
      basis for in depth theoretical analysis required for our objectives. RESULTS:
      There was an almost universal agreement that the integration of secondary care
      advice is important in commissioning. The main perceived barriers were obstacles
      to good communication and relationships, conflicts of interest and financial
      pressures. Participants suggested varied and innovative ways to improve
      communication and integration, and suggestions for organisations. CONCLUSIONS:
      Our results support the importance of secondary care input and highlight
      communication, organisation and integration as three goals for organisations to
      work towards. Successful achievement of these objectives could have financial
      implications for organisations as well as benefits for patient care.

PMID- 23560225
TI  - A rare but important cause of chest pain.

PMID- 23560226
TI  - Acute psychosis caused by hypothyroidism following radioactive iodine treatment
      of Graves' disease.

PMID- 23560227
TI  - Unilateral sino-nasal haemorrhagic polyp masquerading as a malignancy in a boxer.

PMID- 23560228
TI  - Durable cell: a case of multiple AA battery ingestion as a mode of deliberate
      self-harm.

PMID- 23560229
TI  - Vallecular cysts: a differential diagnosis to consider for neonatal stridor and
      failure to thrive.

PMID- 23560230
TI  - Aspirin treatment failure: is this a real phenomenon? A review of the aetiology
      and how to treat it.
AB  - Multiple clinical trials have shown that aspirin can reduce all cardiovascular
      events in primary and secondary prevention and yet there is a large population in
      whom aspirin fails. This review brings together the evidence and controversies
      surrounding the definition of 'aspirin treatment failure', its clinical
      significance and the possible approaches to managing such patients. Several
      different assays have been developed to measure the biochemical action of
      aspirin. At present there is no 'gold standard' and there is massive disparity
      between methods. Studies thus far have shown inconsistent results and to date the
      treatment of aspirin therapy failure is left to the discretion of the leading
      physician.

PMID- 23560231
TI  - The immune modulating properties of the heat shock proteins after brain injury.
AB  - Inflammation within the central nervous system often accompanies ischemia,
      trauma, infection, and other neuronal injuries. The immune system is now
      recognized to play a major role in neuronal cell death due to microglial
      activation, leukocyte recruitment, and cytokine secretion. The participation of
      heat shock proteins (Hsps) in the immune response following in brain injury can
      be seen as an attempt to correct the inflammatory condition. The Hsps comprise
      various families on the basis of molecular size. One of the most studied is
      Hsp70. Hsp70 is thought to act as a molecular chaperone that is present in almost
      intracellular compartments, and function by refolding misfolded or aggregated
      proteins. Hsps have recently been studied in inflammatory conditions. Hsp70 can
      both induce and arrest inflammatory reactions and lead to improved neurological
      outcome in experimental brain injury and ischemia. In this review, we will focus
      on underlying inflammatory mechanisms and Hsp70 in acute neurological injury.

PMID- 23560232
TI  - Gastric stem cells and gastric cancer stem cells.
AB  - The gastric epithelium is continuously regenerated by gastric stem cells, which
      give rise to various kinds of daughter cells, including parietal cells, chief
      cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The
      self-renewal and differentiation of gastric stem cells need delicate regulation
      to maintain the normal physiology of the stomach. Recently, it was hypothesized
      that cancer stem cells drive the cancer growth and metastasis. In contrast to
      conventional clonal evolution hypothesis, only cancer stem cells can initiate
      tumor formation, self-renew, and differentiate into various kinds of daughter
      cells. Because gastric cancer can originate from gastric stem cells and their
      self-renewal mechanism can be used by gastric cancer stem cells, we review here
      how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth
      factor, and bone morphogenetic protein signaling, may regulate the self-renewal
      and differentiation of gastric stem cells and gastric cancer stem cells. In
      addition, the precancerous change of the gastric epithelium and the status of
      isolating gastric cancer stem cells from patients are reviewed.

PMID- 23560233
TI  - Molecular regulation of kidney development.
AB  - Genetically engineered mice have provided much information about gene function in
      the field of developmental biology. Recently, conditional gene targeting using
      the Cre/loxP system has been developed to control the cell type and timing of the
      target gene expression. The increase in number of kidney-specific Cre mice allows
      for the analysis of phenotypes that cannot be addressed by conventional gene
      targeting. The mammalian kidney is a vital organ that plays a critical
      homeostatic role in the regulation of body fluid composition and excretion of
      waste products. The interactions between epithelial and mesenchymal cells are
      very critical events in the field of developmental biology, especially renal
      development. Kidney development is a complex process, requiring inductive
      interactions between epithelial and mesenchymal cells that eventually lead to the
      growth and differentiation of multiple highly specialized stromal, vascular, and
      epithelial cell types. Through the use of genetically engineered mouse models,
      the molecular bases for many of the events in the developing kidney have been
      identified. Defective morphogenesis may result in clinical phenotypes that range
      from complete renal agenesis to diseases such as hypertension that exist in the
      setting of grossly normal kidneys. In this review, we focus on the growth and
      transcription factors that define kidney progenitor cell populations, initiate
      ureteric bud branching, induce nephron formation within the metanephric
      mesenchyme, and differentiate stromal and vascular progenitors in the metanephric
      mesenchyme.

PMID- 23560234
TI  - Spatial relationship between expression of cytokeratin-19 and that of connexin-43
      in human fetal kidney.
AB  - Connexin-43, a major gap junction protein, and cytokeratin-19, one of the
      intermediate filament keratins, are known to be markers of well-differentiated
      epithelium. In this study, we investigated the expression of these markers in the
      head region, lungs, and abdominal organs of 10 human mid-term fetuses. The
      expression of connexin-43 was found to be restricted to the dura mater, kidney,
      and adrenal cortex. In the kidney, we found a clear site-dependent difference in
      the expression pattern of these markers: connexin-43 expression was observed in
      the tubules of the renal cortex whereas cytokeratin-19 was strongly expressed in
      the collecting ducts and renal pelvis. This difference remained unchanged
      throughout the fetal stages examined. Immunoreactivity was not observed for
      either of the markers in the intrarenal vessels, including the glomeruli, and
      mesangial cells. Connexin-43 expression seemed to be restricted to the
      metanephric vesicle-derived structures that differentiate in the urogenital ridge
      of the splanchnic mesoderm. The adrenal cortex also originates from the same para
      aortic mesoderm. In contrast, in the urogenital organs, cytokeratin-19 seemed to
      be expressed in ducts derived from the urogenital sinus.

PMID- 23560235
TI  - Distribution of elastic fibers in the head and neck: a histological study using
      late-stage human fetuses.
AB  - There is little or no information about the distribution of elastic fibers in the
      human fetal head. We examined this issue in 15 late-stage fetuses (crown-rump
      length, 220-320 mm) using aldehyde-fuchsin and elastica-Masson staining, and we
      used the arterial wall elastic laminae and external ear cartilages as positive
      staining controls. The posterior pharyngeal wall, as well as the ligaments
      connecting the laryngeal cartilages, contained abundant elastic fibers. In
      contrast with the sphenomandibular ligament and the temporomandibular joint disk,
      in which elastic fibers were partly present, the discomalleolar ligament and the
      fascial structures around the pterygoid muscles did not have any elastic fibers.
      In addition, the posterior marginal fascia of the prestyloid space did contain
      such fibers. Notably, in the middle ear, elastic fibers accumulated along the
      tendons of the tensor tympani and stapedius muscles and in the joint capsules of
      the ear ossicle articulations. Elastic fibers were not seen in any other muscle
      tendons or vertebral facet capsules in the head and neck. Despite being composed
      of smooth muscle, the orbitalis muscle did not contain any elastic fibers. The
      elastic fibers in the sphenomandibular ligament seemed to correspond to an
      intermediate step of development between Meckel's cartilage and the final
      ligament. Overall, there seemed to be a mini-version of elastic fiber
      distribution compared to that in adults and a different specific developmental
      pattern of connective tissues. The latter morphology might be a result of an
      adaptation to hypoxic conditions during development.

PMID- 23560236
TI  - Qualitative changes in fetal trabecular meshwork fibers at the human iridocorneal
      angle.
AB  - We examined a series of changes that occur in the trabecular meshwork fibers of
      human eyes during fetal development at 12-30 weeks of gestation. At 12 and 15
      weeks, the uveal meshwork was stained black with silver impregnation (indicating
      the predominance of collagen types III and IV) in the endomysium of the ciliary
      muscle. At 20 weeks, in combination with Schlemm's canal, a dense fibrous tissue
      mass corresponding to the trabecular meshwork anlage appeared and was colored
      black. The anlage was continuous with the corneal endothelium rather than with
      the ciliary muscle. Until 25 weeks, the trabecular meshwork was identifiable as
      fragmented fiber bundles that stained red-black, suggesting a mixture of collagen
      types I, III, and IV. At 30 weeks, half of the ciliary muscle fibers were
      inserted into the scleral spur and not into the meshwork. Therefore, any
      contribution of ciliary muscle contraction to the differentiation of the
      trabecular meshwork would appear to be limited. We hypothesize that an uneven
      distribution of mechanical stresses in the area of the cornea-sclera junction
      causes a tear thereby creating Schlemm's canal and is accompanied by a change in
      the collagen fiber types comprising the meshwork.

PMID- 23560238
TI  - Expression of transient receptor potential channels in the ependymal cells of the
      developing rat brain.
AB  - Cerebrospinal fluid (CSF) plays an important role in providing brain tissue with
      a stable internal environment as well as in absorbing mechanical and thermal
      stresses. From its initial composition, derived from the amniotic fluid trapped
      by the closure of neuropores, CSF is modified by developing and differentiating
      ependymal cells lining the ventricular surface or forming the choroid plexus. Its
      osmolarity and ionic composition brings about a change through the action of many
      channels expressed on the ependymal cells. Some newly discovered transient
      receptor potential (TRP) channels are known to be expressed in the choroid plexus
      ependyma. To detect additional TRP channel expression, immunohistochemical
      screening was performed at the choroid plexus of 13-, 15-, 17-, and 19-day
      embryos, using antibodies against TRPV1, TRPV3, and TRPA1, and the expression was
      compared with those in the adult TRP channels. The level of TRP channel
      expression was higher in the choroid plexus which suggests more active
      functioning of TRP channels in the developing choroid plexus than the ventricular
      lining ependyma in the 15- and 17-day embryos. All the expression of TRP channels
      decreased at the 19th day of gestation. TRPA1 was expressed at a higher level
      than TRPV1 and TRPV3 in almost all stages in both the choroid plexus and
      ventricular lining epithelium. The highest level of TRPV1 and TRPV3 expression
      was observed in association with the glycogen deposits in the cytoplasm of the
      choroid plexus ependymal cells of the 15- and 17-day embryos.

PMID- 23560239
TI  - Unilateral duplication of vas deferens: a cadaveric case report.
AB  - Duplication of vas deferens is a rare congenital anomaly. All previously reported
      cases of this rare anomaly were identified during procedures such as orchiepexy,
      inguinal hernia repair, vasectomy, varicocoelectomy, and radical prostatectomy.
      Here, we report a case of unilateral duplicated vas deferens noted in an adult
      cadaver during regular dissection for medical students. The right spermatic cord
      contained 2 separate and completely developed cord-like structures. Both cords
      communicated separately with the tail of the epididymis. When traced cranially,
      both traversed the inguinal canal as content of the spermatic cord and finally
      fused at the level of the deep inguinal ring. No other variations were found in
      the testis or epididymis, and no variations were seen in the left spermatic cord.
      In addition, no associated renal abnormalities were noted.

PMID- 23560237
TI  - Caffeine-induced endothelial cell death and the inhibition of angiogenesis.
AB  - Numerous studies have shown that adenosine or adenosine agonists can stimulate
      angiogenesis. However, the effect of caffeine (a known adenosine receptor
      antagonist) on angiogenesis has not been previously studied. Accordingly, this
      study was undertaken to examine the effect of caffeine on angiogenesis and to
      clarify the mechanism involved. Chick chorioallantoic membrane assays were used
      to investigate the effect of caffeine on angiogenesis and proliferation assays
      using human umbilical vein endothelial cells (HUVECs), were used to study its
      effects on specific aspects of angiogenesis. The expressions of caspase-3 and Bcl
      2 were examined by western blotting, immunofluorescence staining was used to
      identify HUVEC morphological changes, and fluorescence activated cell sorting
      (FACS) and DAPI staining were used to detect HUVEC apoptosis. Caffeine was found
      to inhibit blood vessel formation dose-dependently and to inhibit the
      proliferation of HUVECs time- and dose-dependently. FACS analysis and DAPI
      staining showed that inhibitory effect of caffeine on HUVEC proliferation was the
      result of apoptosis and the up-regulation of thrombospondin-1 (TSP-1).
      Furthermore, TSP-1 levels were down-regulated by NECA but were unaffected by
      CGS21680, indicating that caffeine regulated TSP-1 expression via adenosine A2B
      receptor. In addition, caffeine up-regulated caspase-3 and down-regulated Bcl-2
      at the protein level. These results suggest that the inhibitory effect of
      caffeine on angiogenesis is associated, at least in part, with its induction of
      endothelial cell apoptosis, probably mediated by a caspase-3 dependent mechanism.

PMID- 23560240
TI  - A peculiar liver with surgically and radiologically important variations: a case
      report.
AB  - A peculiar liver was found in an adult male cadaver during a dissection class for
      undergraduate medical students. The quadrate lobe and fissure for the ligamentum
      teres were totally absent. Thus, the cystic notch on the inferior border was very
      broad and deep, and the fundus and body of the gall bladder popped out through
      this notch. The cystic duct terminated into the right hepatic duct at the porta
      hepatis instead of terminating into the common hepatic duct. Awareness of
      variations of the lobes and fissures may minimize a misdiagnosis of liver
      problems. The aim of the current study was to alert radiologists and surgeons
      about possible variations in the external appearance and anomalies of the lobes
      and fissures of the liver.

PMID- 23560241
TI  - Assessing Time Diary Quality for Older Couples: An Analysis of the Panel Study of
      Income Dynamics' Disability and Use of Time (DUST) Supplement.
AB  - Using same-day diaries from 394 older couples in the Panel Study of Income
      Dynamics (PSID), this paper develops and explores several new measures of diary
      quality. Two overarching questions are explored: 1) How do diary quality measures
      reflecting the data collection process enhance understanding of time use in later
      life? and 2) How well do same-day diaries from couples match up in terms of
      husbands' and wives' reports of time spent (actively engaged) together? We found
      a summary measure of diary quality indicated only 13.8% of diaries were lower
      quality. Lower quality diaries were more likely to be obtained from older adults
      (ages 70+ vs. 50-69) and first (vs. second) interviews. Joint activities from
      diaries of lower quality were less likely than those from higher quality diaries
      to be matched to an activity on a spouse's same-day diary. However, such a
      measure did not predict time spent in common activities nor did its inclusion
      have any effect on predictors of time use. We also found that among activities
      described as joint by at least one respondent, up to 76% had a matching record in
      the spouse's diary. The quality of matches appeared to be quite good, with the
      majority of matched activities having overlapping times reported by spouses and
      being described as joint by both spouses. Very similar estimates of joint time
      were reported by husbands and wives (about 5-51/2 hours). Implications of
      findings for future methodological and substantive investigations are discussed.

PMID- 23560242
TI  - Diabetes Mellitus and Colorectal Neoplasia.
AB  - BACKGROUND: Many studies have provided evidence for an association between
      obesity, physical inactivity, and western diet as risk factors for colorectal
      cancer (CRC). Few studies directly address the association between type 2
      Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic
      locations. METHODS: 2,663 subjects with a previous history of adenoma(s) and
      removal of all current adenomas at study entry were followed for a mean time of
      three years across three different chemoprevention clinical trials. The primary
      endpoint was colorectal adenoma recurrence and number of lesions during the
      treatment phase; the secondary endpoints were presence of advanced colorectal
      neoplasia (CRN) and location of CRN. Using log linear regression, the effect of
      DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location
      of CRN was assessed. RESULTS: DM status was not significantly associated with
      incidence of colorectal adenomas, incidence of advanced colorectal lesions, or
      left-sided colorectal neoplastic lesions. Subjects with DM had a marginally
      increased risk of right-sided (p= 0.06) colorectal adenomas and a significant
      increased risk of multiple right-sided adenomas (p=0.03) in the unadjusted model;
      this association was not significant after adjusting for age and other potential
      confounders (RR=1.22, 95% CI: 0.85-1.76). CONCLUSION: We did not observe a
      statistically significant increased risk in CRN recurrence for overall neoplasia,
      advanced neoplasia or location of neoplasia in individuals with DM compared to
      non-DM individuals. However, given the patterns observed in this investigation,
      future studies with longer follow-up time and longer DM exposure, incorporating
      objective measurements of type 2 DM might help elucidate the risk of CRN among
      individuals with DM.

PMID- 23560243
TI  - Acceptance of Asthma Pharmacogenetic Study by Children and Adults.
AB  - BACKGROUND: Pharmacogenetic testing may change clinical medicine by allowing
      clinicians to tailor medications based on a patient's genetic makeup, however,
      these tests must first be validated in large, real-life populations of subjects
      that include children. A dearth of knowledge exists for whether pediatric
      populations are as willing as adult populations to provide samples for such
      studies. OBJECTIVE: (1) To assess whether pediatric and adult patients with
      persistent asthma are willing to provide specimens for DNA extraction and genetic
      studies. (2) To assess whether patients' willingness to provide blood as compared
      to buccal smear specimens differ. METHODS: Of 644 patients ages 4-38 years who
      had three or more prescription fills for inhaled corticosteroids in one year, 60%
      (385) were randomized to the blood specimen group and 40% (259) were randomized
      to the buccal smear group in order to study acceptance of different biospecimen
      collection methods. Research assistants contacted subjects to obtain consent,
      perform a phone survey, and request a specimen. RESULTS: There were no baseline
      differences between subjects randomized to the blood specimen group versus buccal
      smear group with respect to age, gender, or number of dispensings of inhaled
      corticosteroids. Of 259 subjects in the buccal smear group, 30% (78) provided
      samples, and of 385 subjects in the blood specimen group, 16% (60) provided
      samples. Subjects randomized to the buccal smear group were more likely to
      provide specimens for genetic study compared to subjects randomized to the blood
      specimen group (RR 1.21; 95% CI 1.10 - 1.32), even after adjusting for age.
      Pediatric subjects were more likely to provide specimens for genetic study than
      adult subjects with 23% (113) of pediatric subjects providing samples and 15%
      (25) of adult subjects providing samples (p=0.03). CONCLUSION: Children with
      asthma are as likely to participate in genetic studies as adults. Both children
      and adult subjects are more likely to provide buccal smear specimens rather than
      blood specimens for genetic study.

PMID- 23560244
TI  - A Community-Based Approach to Enhancing Anal Cancer Screening in Hawaii's HIV
      Infected Ethnic Minorities.
AB  - OBJECTIVE: Disparities in anal cancer incidence among Hawaii's HIV-infected
      minority population is an emerging health concern. Although anal
      cytology/anoscopy are effective anal cancer screening tools, social barriers
      exist that prevent individuals from seeking appropriate care. DESIGN: Community
      based participatory research (CBPR) principles were applied to develop resources,
      including testing a self-obtained anal specimen procedure, to increase anal
      cancer screening among Hawaii's underserved/ minority populations. METHODS: A
      team of community members, academic researchers, and health care providers
      developed culturally-sensitive educational/recruitment materials regarding anal
      cancer risk targeting underserved/minority HIV-infected individuals. Self- and
      health care provider (HCP)-obtained anal cancer screening specimens were reviewed
      for cytology and tested for human papillomavirus DNA. A follow-up evaluation
      elicited feedback on attitudes and experiences. RESULTS: Community discussion
      sessions identified key messages about anal cancer, anal cancer screening, and
      HPV infection for materials and were used, that successfully recruited 46
      individuals (38 males/8 females; 9 Native Hawaiians/Pacific Islanders/Asians, 2
      Blacks, 6 Hispanics, 6 American Indian/Alaskan Natives, 23 Whites). Concordance
      in cytology results between self- and HCP-obtained specimens was moderated
      (kappa=0.37) with the perception that the self-obtained specimen procedure was
      private (93%), safe (100%), and easy to manage (100%); and a majority (92%)
      willing to use the self-obtained method again. CONCLUSIONS: CBPR was a practical
      approach in engaging Hawaii's HIV-infected minority participation in anal cancer
      screening research. Community outreach and recruitment efforts suggested that
      self-obtained screening specimens could be an acceptable and effective means to
      reach Hawaii's HIV-infected ethnic minorities.

PMID- 23560245
TI  - Extracellular Matrix Protein Mindin is Required for the Complete Allergic
      Response to Fungal-Associated Proteinase.
AB  - Asthma remains an important cause of morbidity and mortality with an incidence
      that continues to rise. Despite the importance of this disease, the mechanisms by
      which the host develops allergic airways disease remain poorly understood. The
      development of allergic airways disease appears to be contingent on activation of
      both the innate and adaptive immune system, but little is known about the cross
      talk between these two systems. The extracellular matrix protein mindin (Spondin
      2) has been previously demonstrated to have functional roles in both the innate
      and adaptive immunological responses. Previous work supports that pulmonary
      challenge with fungal-associated allergenic proteinase (FAP) induces an innate
      allergic response. We hypothesized that mindin would modify the biological
      response to FAP. Saline or FAP was administered by oropharyngeal aspiration to
      C57BL/6 wild type or mindin-null mice every 4 days for a total of five exposures.
      FAP exposed C57BL/6 mice developed enhanced airway hyperresponsiveness (AHR) to
      methacholine challenge and increased neutrophils and eosinophils in the
      bronchoalveolar lavage as compared to saline exposed controls. These responses
      were significantly reduced in mindin-null mice exposed to FAP. FAP challenge was
      associated with a broad induction of cytokines (IL-1beta, TNFalpha, Th1, Th2, and
      IL-17), chemokines, and growth factors, which were reduced in mindin-null mice
      exposed to FAP. RNA expression in lung monocytes for representative M1 and M2
      activation markers were increased by FAP, but were independent of mindin. Our
      observations support that challenge with FAP results in activation of both innate
      and adaptive immune signaling pathways in a manner partially dependent on mindin.
      These findings suggest a potential role for the extracellular matrix protein
      mindin in cross-talk between the innate and adaptive immune systems.

PMID- 23560246
TI  - Airway Hyperresponsiveness and Inflammation: Causation, Correlation, or No
      Relation?
AB  - Asthma represents a growing problem in the developing world, affecting millions
      of children and adults. Features of the disease are reversible airflow
      obstruction, airway hyperresponsiveness and airway inflammation leading to tissue
      damage and remodeling. Many studies have attempted to address whether
      inflammation and airway hyperresponsiveness are mechanistically linked. In this
      study, data are presented from several mouse models that illustrate that a clear
      link between these features of asthma remains elusive. The impact of altering
      inflammatory signaling (NF-kappaB or JNK1) on inflammation and airway
      hyperresponsiveness was examined. In addition, the effect of antigen
      sensitization and the route of antigen delivery were investigated. The data
      herein show that in many cases, inflammation and airway hyperresponsiveness do
      not directly correlate. In conclusion, the need for mechanistic studies in mouse
      models is highlighted to address the interplay between these components thought
      to be critical to asthma pathogenesis.

PMID- 23560247
TI  - Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface
      Disease under Experimental Murine Dry Eye.
AB  - OBJECTIVE: Continuous drug delivery to the ocular surface remains difficult due
      to the rapid tear clearance of topically applied agents. The purpose of this
      study was to evaluate biodegradable and biocompatible drug delivery systems on
      the ocular surface using poly-lactic-co-glycolic acid (PLGA) based polymers.
      METHODS: Fluorescein-labeled albumin and doxycycline were individually
      encapsulated into a PLGA-based matrix using a water-oil-water double emulsion
      method. The drug elution rates for various microspheres were evaluated
      spectrofluorometrically. Particle size was measured using image analysis
      software. Subconjunctival injections of PLGA microspheres were used to evaluate
      safety and inflammatory response to the polymer in the murine model. Efficacy of
      the drug delivery system was evaluated by a single subconjunctival injection of
      PLGA-doxycycline (a broad metalloproteinase inhibitor) prior to induction of
      desiccating stress (DS) model in C57BL/6 mice for 5 days. RESULTS: PLGA-based
      microspheres successfully elute encapsulated drugs of interest continuously over
      controlled periods of time. Mean PLGA-based microparticle diameter was 4.6 MUm+/
      1.54 MUm. Drug elution rates and delivery times were easily modifiable by
      altering polymers and synthesis parameters. In vitro studies demonstrate
      successful continuous elution of encapsulated drugs for at least 2 weeks. In vivo
      testing of PLGA-doxycycline was efficacious in preventing DS-induced corneal
      barrier disruption with desiccating stress, similarly to topically applied
      doxycycline. CONCLUSIONS: PLGA-based drug delivery systems are safe and non
      inflammatory. They can be successfully used to treat ocular surface and corneal
      diseases by continuously delivering biopharmaceuticals of interest.

PMID- 23560249
TI  - Retraction: On soft expert topological spaces.

PMID- 23560248
TI  - The Sirtuin System: The Holy Grail of Resveratrol?
AB  - The oxidative stress theory has been associated with atherosclerosis and has
      prompted a multitude of studies to evaluate the effects of antioxidants on
      cardiovascular disease prevention. Resveratrol, a relatively new antioxidant has
      gained considerable curiosity. This polyphenol stilbene identified in grape skin,
      is believed to be the main component contributing to the anti-atherosclerotic
      benefits linked to red wine consumption. It has demonstrated the ability to
      protect endothelial cells from lipid damage, promote vasodilation via modulation
      of nitric oxide synthesis, and inhibit platelet aggregation and smooth muscle
      proliferation. Although the complete mechanism of Resveratrol has yet to be fully
      elucidated, the Sirtuin system, consisting of 7 highly conserved families of
      regulator genes, are thought to be instrumental in establishing the various
      health benefits. In this article we assess the current applications, mechanism,
      pharmacokinetics, bioavailability, and safety profile of the novel antioxidant
      Resveratrol and provide an in-depth review of the influence of the Sirtuin system
      on the Resveratrol mechanism of action. We resolve that while early data on
      Resveratrol are promising, the anti-oxidative and ultimately, anti
      atherosclerotic potential depends on further clarification of the intricate and
      complex relationship between Resveratrol and the Sirtruin system.

PMID- 23560250
TI  - The combination of Ki67, histological grade and estrogen receptor status
      identifies a low-risk group among 1,854 chemo-naive women with N0/N1 primary
      breast cancer.
AB  - BACKGROUND: The aim was to confirm a previously defined prognostic index,
      combining a proliferation marker, histological grade, and estrogen receptor (ER)
      in different subsets of primary N0/N1 chemo-naive breast cancer patients.
      METHODSDESIGN: In the present study, including 1,854 patients, Ki67 was used in
      the index (KiGE), since it is the generally accepted proliferation marker in
      clinical routine. The low KiGE-group was defined as histological grade 1 patients
      and grade 2 patients which were ER-positive and had low Ki67 expression. All
      other patients made up the high KiGE-group. The KiGE-index separated patients
      into two groups with different prognosis. In multivariate analysis, KiGE was
      significantly associated with disease-free survival, when adjusted for age at
      diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95%
      confidence interval: 2.6-4.7, P<0.0001). DISCUSSION: We have confirmed a
      prognostic index based on a proliferation marker (Ki67), histological grade, and
      ER for identification of a low-risk group of patients with N0/N1 primary breast
      cancer. For this low-risk group constituting 57% of the patients, with a five
      year distant disease-free survival of 92%, adjuvant chemotherapy will have
      limited effect and may be avoided.

PMID- 23560251
TI  - Revealing substituent effects on the electronic structure and planarity of Ni
      porphyrins.
AB  - Using density functional theory, we have studied the effects on structural and
      electronic consequences (including HOMO-LUMO energy gaps, vertical ionization
      potentials (IPv), and vertical electron affinities (EAv)) of the following two
      factors: (a) meso- and beta-substituents acting as inductive donors (CH3),
      inductive acceptors that are electron-donating through resonance (Br), inductive
      electron acceptors (CF3), and resonance enabled acceptors (NO2); and (b) complete
      replacement of pyrrole nitrogens with P-atoms. The principal results of the study
      are: (1) For the bare Ni-porphyrin, the solvents were found not to affect the
      HOMO-LUMO gaps but to change the IPv and EAv noticeably. (2) In the series CH3 ->
      Br -> CF3 -> NO2 the HOMO-LUMO energy gaps, IPv, and EAv increase for both meso-
      and beta-substituents. The ruffling distortion of the porphyrin core is retained,
      and becomes stronger for the two acceptor groups. In general, effects of meso
      substituents on the ruffling distortion of the porphyrin core is more pronounced.
      (3) Most significantly, complete replacement of pyrrole nitrogens in the NiP with
      phosphorus atoms produces the species, NiP(P)4, with the structural and
      electronic features drastically different from the original NiP. This implies
      that NiP(P)4 can possess interesting and unusual novel properties, including
      aromaticity and reactivity, leading to its various beneficial potential
      applications. Furthermore, NiP(P)4 high stability both in the gas phase and
      different solvents was shown, implying the feasibility of its synthesis.

PMID- 23560252
TI  - Polymerization shrinkage stresses in a premolar restored with different composite
      resins and different incremental techniques.
AB  - PURPOSE: To investigate how the incremental filling technique, elastic modulus,
      and post-gel shrinkage of different dental composite resins affect residual
      shrinkage stress in a restored premolar. MATERIALS AND METHODS: Sixteen
      composites indicated for restoring posterior teeth were tested. Elastic modulus
      and Knoop hardness were measured using Knoop indentation tests (n = 10). A strain
      gauge test was used to measure the post-gel shrinkage (n = 10). Two incremental
      techniques, horizontal or oblique, were applied in a finite element model of a
      premolar in combination with the experimentally determined properties to assess
      the stress conditions along the interface of the restoration and within the
      material structures. Linear regressions were determined between residual
      shrinkage stress and the elastic modulus and post-gel shrinkage values. RESULTS:
      The mechanical properties and the post-gel shrinkage varied significantly among
      the composites tested. The calculated shrinkage stress showed a strong
      correlation with post-gel shrinkage and a weaker correlation with elastic
      modulus. The oblique incremental filling technique resulted in lower residual
      shrinkage stress in the enamel and dentin and along the enamel/composite
      interface compared to the horizontal technique. CONCLUSION: Residual stress
      varied significantly among the contemporary dental composites indicated for
      restoring posterior teeth. Shrinkage stress in a restored tooth correlated with
      post-gel shrinkage. In general, oblique incremental filling resulted in lower
      residual stresses than did horizontal increments.

PMID- 23560253
TI  - Effect of various aging protocols and intermediate agents on the bond strength of
      repaired composites.
AB  - PURPOSE: To evaluate the effect of two adhesive systems and different aging
      protocols on the bond strength of a -repaired microhybrid composite. MATERIALS
      AND METHODS: Eighty test specimens (n = 20) and 10 control specimens measuring 8
      x 4 mm were fabricated of a microhybrid composite (4 Seasons, shade A2) and
      grouped according to time/aging protocol: G1: 24 h in artificial saliva; G2: 7
      days in artificial saliva; G3: 30 days in artificial saliva; G4: artificial
      accelerated aging (AAA) for 384 h; G5: control. After aging, samples were
      submitted to three types of surface treatment: SB2: Adper Single Bond 2, a two
      step adhesive (3M ESPE); SB3: Adper Scotchbond Multi-Purpose, a three-step
      adhesive (3M ESPE); C: without application of adhesive (control). After this,
      test specimens were repaired with the same composite of a different shade (C3),
      and submitted to the microtensile test at a crosshead speed of 0.5 mm/min.
      Failure modes were analyzed by scanning electron microscopy (Jeol JSM 7500).
      Statistical analysis was performed using ANOVA and Tukey's test (p < 0.05).
      RESULTS: G2/SB2 presented significantly lower bond strength values in comparison
      with the other groups (p < 0.05). The control group presented the highest bond
      strength values, which differed statistically significantly from SB3, G3/SB2, and
      G4/SB2 (p < 0.05). Fractographic analysis demonstrated that most samples
      presented predominantly cohesive failures, excepting GI/SB2, which presented
      mixed and cohesive failures, and G4/SB2 and G1/SB3, which showed adhesive
      failures. CONCLUSION: The repair was more effective when performed after a short
      period of time and when the 3-step adhesive system (SB3) was used.

PMID- 23560254
TI  - Effect of hygroscopic expansion of resin filling on interfacial gap and sealing:
      a confocal microscopy study.
AB  - PURPOSE: To measure dimensional changes due to hygroscopic expansion and their
      effect on interface gaps and sealing in four light-cured restorative materials
      using an original confocal microscopic methodology. MATERIALS AND METHODS: The
      materials tested were an ormocer (Admira [Voco]), a compomer (Dyract AP
      [Dentsply]), a hybrid composite (Spectrum [Dentsply]), and a nanohybrid composite
      (Esthet.X [Dentsply]). Water sorption was evaluated by weighing material disks
      after immersion. Hygroscopic expansion was measured from volumetric variations of
      material fillings in cylindrical cavities in dentin slices; the interfacial gap
      size was obtained from the same cavities using a novel confocal microscopic
      method. Microleakage was evaluated in cavities prepared in extracted third
      molars. Measurements followed water immersion for 24 h, 1 week, 4 weeks, and 8
      weeks. A factorial ANOVA, the Student Newman Keuls test for post-hoc comparisons,
      the Student's t-test, and the Pearson test were used for the statistical analysis
      (p < 0.05). RESULTS: Positive correlations were found among water sorption,
      hygroscopic expansion, and sealing. Hygroscopic expansion reduced post
      polymerization interfacial gaps and improved cavity sealing. Dyract AP and Admira
      showed the highest water sorption, hygroscopic expansion, and gap size reduction.
      CONCLUSIONS: 1. The proposed methodology is valid to measure hygroscopic
      expansion and interfacial gap. 2. Water sorption and hygroscopic expansion are
      positively correlated, and hygroscopic expansion, gap size, and sealing are also
      positively correlated. 3. The adhesive influences the interfacial gap size and
      its variation after hygroscopic expansion. 4. Hygroscopic expansion reduces the
      interfacial gaps generated by polymerization shrinkage and improves cavity
      sealing.

PMID- 23560255
TI  - In vitro comparison of mechanical properties and degree of cure of a self
      adhesive and four novel flowable composites.
AB  - PURPOSE: To compare a self-adhesive with two low-shrinkage and two regular
      flowable resin-based composites (RBCs) in terms of degree of conversion (DC) as
      well as micromechanical (indentation modulus [E]; Vickers hardness [HV]) and
      macromechanical properties (flexural strength [sigma], modulus of elasticity
      [Eflexural]). MATERIALS AND METHODS: DC was investigated by an ATR-FTIR
      spectrometer at clinically relevant filling depths (0.1 mm, 2 mm, 4 mm, 6 mm
      bulk, 6 mm incremental) and irradiation times (10 s, 20 s, 40 s). Micro- and
      macromechanical properties were measured with an automatic microhardness indenter
      and a three-point bending test device after curing the specimens for 20 s and
      storing them in distilled water for 24 h at 37 degrees C. Fillers were visualized
      using a field emission scanning electron microscope (FE-SEM). Results were
      evaluated using one-way ANOVA, Tukey's HSD post-hoc test, Pearson's correlation
      and a multivariate analysis (alpha = 0.05). A Weibull analysis was used to assess
      sigma. RESULTS: N'Durance Dimer flow (65.66%) reached the highest DC (at 2 mm
      depth, 20 s irradiation). In terms of macromechanical properties, EcuSphere-Flow
      (129.82 MPa) for sigma and Synergy D6 Flow (3.74 GPa) for Eflexural reached the
      highest values. The highest micromechanical properties were measured for the self
      adhesive RBC (Vertise Flow; E = 10.81 GPa, HV = 60.20 N/mm2). Reliability was
      highly influenced by filler weight (eta2 = 0.77) and volume (eta2 = 0.99)
      proportion. CONCLUSION: In the present study, the self-adhesive RBC showed the
      highest reliability, highest DC (together with one of the low-shrinkage RBCs),
      and highest micromechanical properties as well as good macromechanical
      properties. Moreover, a curing time of 40 s and an incremental thickness not
      exceeding 2 mm appeared to be necessary for such results.

PMID- 23560256
TI  - Effect of polyacrylic acid on the interface and bond strength of self-adhesive
      resin cements to dentin.
AB  - PURPOSE: To examine the influence of 11.5% polyacrylic acid pretreatment on the
      interface and bond strength of self-adhesive resin cements (Maxcem Elite, RelyX
      Unicem, SeT) to dentin. MATERIALS AND METHODS: Fifty-six third molars were
      randomly divided into seven groups: RelyX ARC as control (ARC), RelyX Unicem
      (RLXU), Maxcem Elite (MCE), SeT (ST), polyacrylic acid+RelyX Unicem (RLXU-P),
      polyacrylic acid+Maxcem Elite (MCE-P), and polyacrylic acid+SeT (ST-P). Resin
      composite blocks were luted to flat dentin. After storage in distilled water for
      24 h, sticks with a cross-sectional area of ca 0.80 mm2 were obtained (n = 24 per
      group) and submitted to a microtensile bond strength (uTBS) test in a universal
      testing machine at a crosshead speed of 0.5 mm/min. Two sets from each group were
      sectioned mesiodistally in the center of the crown and observed with a scanning
      electron microscope at 4000X magnification. RESULTS: The mean results of the uTBS
      test (MPa) followed by the same letter do not differ statistically significantly
      according to ANOVA and Tukey's post-hoc test (p < 0.05): ARC = 24.19 (+/- 6.90)a,
      RLXU-P = 23.12 (+/- 6.18)a, MCE-P = 13.09 (+/- 5.87)b, RLXU = 10.23 (+/-
      2.88)b,c, and MCE = 8.14 (+/- 4.63)c. All SeT specimens failed during the cutting
      procedure. The hybrid layer was not observed for the self-adhesive resin cements,
      and resin tags were observed for RelyX Unicem and Maxem Elite when dentin was
      pretreated with polyacrylic acid. CONCLUSION: Pretreatment with 11.5% polyacrylic
      acid was effective for bonding RelyX Unicem and Maxcem Elite to dentin.

PMID- 23560257
TI  - Effect of the flavonoid epigallocatechin-3-gallate on resin-dentin bond strength.
AB  - PURPOSE: To evaluate the effect of dentin pretreatment with epigallocatechin-3
      gallate solution on the preservation of the resin/dentin interface with etch-and
      rinse adhesives. MATERIALS AND METHODS: Thirty extracted human molars were
      prepared to expose the dentin surface and divided into 5 groups according to the
      pretreatment solution. Dentin surfaces were etched (35% phosphoric acid for 15
      s), rinsed, and air dried. Dentin was rewetted either with distilled water, 3
      different epigallocatechin-3-gallate solutions (EGCG; 0.02%, 0.1%, or 0.5% w/v),
      or 2% chlorhexidine digluconate solution for 60 s. Adper Single Bond 2 was
      applied and a subsequent 5-mm-thick resin crown was built up. Bonded teeth were
      longitudinally sectioned to obtain sticks with a cross-sectional area of 1.0 mm2.
      Half of the specimens were immediately tested, while the remaining specimens were
      tested after storage in 3 mMol/l sodium azide solution at 37 degrees C for six
      months. The mode of fracture was examined. Bond strength values were analyzed
      with ANOVA and Student-Newman-Keuls tests. RESULTS: After 24 h of storage, mean
      bond strengths of 0.5% EGCG were significantly lower than those found for the
      other groups (p < 0.05), except for 0.02% EGCG (p > 0.05). Resin-dentin bond
      strengths after 6 months were not significantly different among the experimental
      groups (p > 0.05). Storage in water for 6 months resulted in a significant
      decrease in bond strength for the water control group only (p < 0.05). The bond
      strengths of the experimental groups remained stable after 6 months of water
      storage (p > 0.05). CONCLUSION: Pretreatment with EGCG preserved the bond of
      Adper Single Bond 2 to dentin after six months of storage equally well as
      pretreatment with chlorhexidine digluconate.

PMID- 23560258
TI  - Effect of chlorhexidine on the 18-month clinical performance of two adhesives.
AB  - PURPOSE: This study tested the hypothesis that 2% chlorhexidine (CHX) does not
      affect the 18-month clinical performance of two dentin adhesives, XP Bond (XPB)
      and XENO V (XEN). MATERIALS AND METHODS: A total of 120 noncarious cervical
      lesions (NCCL) were selected and assigned to 4 groups: (1) XPB; (2) CHX prior to
      the application of XPB; (3) XEN; (4) CHX prior to the application of XEN. A
      hybrid composite resin, Esthet?X, was used for all restorations. Restorations
      were evaluated blindly at 6 and 18 months by two evaluators using the University
      of North Carolina (UNC)-modified USPHS criteria. Statistical analyses included
      the Mann Whitney and McNemar nonparametric tests (p < 0.05). RESULTS: At 6
      months, 91 (75.2%) restorations were evaluated, while 92 (76.7%) restorations
      were evaluated at 18 months. The 6-month/18-month overall retention rates (%)
      were 100/100 for XPB, 96.0/95.0 for CHX+XPB, 100/91.3 for XEN, and 100/95.8 for
      CHX+XEN with no statistical difference between any pair of groups at each recall.
      Sensitivity to air improved significantly for groups XPB, XEN, and CHX+XEN from
      pre-operative conditions to 1 week after insertion, to 6 and to 18 months after
      inserting. For group CHX+XPB, there was a statistically significant difference
      only between pre-operative conditions and 1 week after insertion. Marginal
      adaptation deteriorated for all groups, but no statistically significant
      differences were found. All other criteria remained statistically similar.
      CONCLUSION: The application of CHX prior to the dentin adhesive did not influence
      the 6-month/18-month clinical performance of the two adhesives.

PMID- 23560259
TI  - Biomimetically- and hydrothermally-grown HAp nanoparticles as reinforcing fillers
      for dental adhesives.
AB  - PURPOSE: Differently prepared hydroxyapatite (HAp) nanoparticles were
      incorporated into the adhesive solution of a commercial adhesive system in order
      to evaluate the effect on microtensile bond strength to dentin. MATERIALS AND
      METHODS: HAp nanoparticles (20 to 70 nm) were prepared by different processes
      (biomimetic and hydrothermal) and incorporated into the adhesive of the Adper
      Scotchbond Multi-Purpose (SBMP) system at various concentrations. Control
      (unfilled) and experimental groups (filled) were applied onto flat mid-coronal
      human dentin. Composite crowns were built up and cut into beams with a cross
      sectional area of 0.65 +/- 0.05 mm2. Specimens were fractured in tension and
      examined with a scanning electron microscope (SEM) for fractographic analysis.
      Microtensile bond strength (uTBS) data were analyzed using a two-way ANOVA and
      modified LSD test at a = 0.05. Analysis of the nanofiller distribution and
      ultramorphological characterization of the interface was performed by
      transmission electron microscopy (TEM). RESULTS: HAp nanoparticle incorporation
      into the adhesive of SBMP significantly influenced uTBS to dentin depending on
      the fillers and the concentration used. A significant increase of the mechanical
      strength was obtained for the adhesives containing 1% (wt/vol) biomimetic and 5%
      hydrothermal silanized HAp particles, while the other particle fractions did not
      influence uTBS significantly. 10% (wt/vol) HAp particles significantly lowered
      the uTBS irrespective of the particle type used. TEM micrographs revealed
      nanoparticle dispersion through the adhesive layer but no deposition on or
      penetration into the hybrid layer. CONCLUSIONS: HAp nanoparticle incorporation
      into SBMP increased bond strength to dentin by cohesively reinforcing the
      interface adhesive layer. At a concentration of 10% (wt/vol), nanofiller
      incorporation had a negative effect on bond strength.

PMID- 23560260
TI  - Dentin matrix component solubilization by solutions of pH relevant to self
      etching dental adhesives.
AB  - PURPOSE: To evaluate the potential for phosphoric acid solutions - common
      constituents of dental adhesive systems - of varying pH to solubilize dentin
      matrix components (DMCs) from human dentin. MATERIALS AND METHODS: Human dentin
      chips were ground under liquid nitrogen to a powder (ca 100 um) and incubated at
      4 degrees C with agitation in phosphoric acid of pH 1, 2, 3, 4, 5, and 6 (1 g/4
      ml; n = 4) for six days with solution changes each day. Estimates of daily
      protein release were made by UV spectrophotometry at 280 nm. Extract solutions
      were dialyzed for 7 days in reverse osmosis water, lyophilized, and weighed. Non
      collagenous proteins (NCPs) and glycosaminoglycans (GAGs) were quantitated by dye
      binding assays. 1D-PAGE for preliminary protein characterization and sandwich
      ELISA for presence of TGF-beta1 were performed. The results were analyzed by
      ANOVA and regression (alpha <= 0.05). RESULTS: Protein release was drastically
      reduced after the first few days, with the highest amounts obtained from pH 1.
      There was no significant difference in the quantity of DMCs solubilized by the
      different pH levels, but there was a significant logarithmic relation between
      release and pH, suggesting that greater DMC solubilization occurs with higher
      hydrogen ion concentrations. Dye binding assays confirmed the release of NCPs and
      GAGs at all pH levels. There were only subtle differences in protein bands
      observed between the different pH levels (1D-PAGE). Significant levels of TGF
      beta1 were identified from extraction at all pHs. CONCLUSION: Acids at pH levels
      relevant to those used in commercial dentin adhesives are capable of solubilizing
      human DMCs, with release being related to hydrogen ion concentration.

PMID- 23560262
TI  - Editors talk to each other.

PMID- 23560261
TI  - Polymerization kinetics of dual-curing adhesive systems when used solely or in
      conjunction with chemically-cured resin cement.
AB  - PURPOSE: To investigate the chemical polymerization kinetics of commercial dual
      curing adhesive systems when used solely or in conjunction with chemically-curing
      resin cement. MATERIALS AND METHODS: Four adhesive systems comprising simplified
      step adhesives and activators (Prime&Bond NT with Self Cure Activator, Excite
      DSC, AQ Bond Plus, All-Bond SE) were used. The pH values of the adhesives and
      adhesive/activator blends were measured. Differential scanning calorimetry (DSC)
      was used to investigate the extent of the chemical polymerization of the
      adhesives when used alone or directly intermixed with a chemically-cured resin
      cement (C&B Cement) for 60 min (n = 5). The data derived from the DSC analysis
      were statistically compared using one-way ANOVA and the Games-Howell post-hoc
      test (alpha = 0.05). RESULTS: All the adhesives were highly acidic; when they
      were blended with the respective activators, their pH values increased. Neither
      the adhesive/activator blends nor the adhesive alone/cement mixtures showed any
      detectable heat generation. The Prime&Bond NT/activator showed delayed heat
      generation only when intermixed with the catalyst/base paste. The other three
      adhesive systems produced similar exotherms when intermixed with the catalyst
      paste alone or with the catalyst/base paste (p > 0.05), but at significantly
      different maximum rates of polymerization (p < 0.05). Significantly shorter
      induction periods resulted when AQ Bond Plus and All- Bond SE were intermixed
      with the catalyst/base paste rather than with the catalyst paste alone (p =
      0.004). CONCLUSION: The chemical polymerization occurring at the adhesive
      system/resin cement interface appears highly dependent on the adhesive system
      used and may be considerably delayed.

PMID- 23560263
TI  - Editorial: Give teeth a chance!

PMID- 23560264
TI  - [Changing times].

PMID- 23560265
TI  - [The arts prosper in times of peace! But the fittest win in hard times!].

PMID- 23560266
TI  - [Thoracoscopic sympathectomy for hyperhidrosis].
AB  - BACKGROUND: Primary hyperhidrosis affects between 1 and 3% of the population. It
      is a problem of sympathetic deregulation which is characterized by profuse
      sweating on the palmar surface of the hands, armpits, groin and feet. The
      therapeutic options for the management of hyperhidrosis have traditionally been
      non-operative. However, there are several studies demonstrating that primary
      hyperhidrosis is best treated by endoscopic thoracic sympathectomy. METHODS: This
      article presents a review of existing approaches and techniques of thoracoscopic
      sympathectomy for treatment of hyperhidrosis as well as the author's summary and
      preferences. RESULTS: Thoracoscopic sympathectomy is now the standard procedure
      chosen for the treatment of severe hyperhidrosis. It is safe and successful in
      almost 98% of cases and only 1-2% of patients experience recurrence. All patients
      develop some degree of compensatory sweating after surgery. In most this is mild
      and tolerable; however, in 3-5% of patients it is severe and intolerable. The
      patients should be made aware that the most satisfied patients are those with
      preoperative palmar or palmar- axillary hyperhidrosis. DISCUSSION: The best
      segment interrupted for the treatment of primary hyperhidrosis, is still
      controversial. The recent body of literature suggests that the highest success
      rates occur when interruption is performed at the top of R3 or the top of R4 for
      palmar hyperhidrosis. R4 may offer a lower incidence of compensatory
      hyperhidrosis but moister hands. For palmar and axillary and only axillary
      hyperhidrosis interruptions at R4 and R5 are recommended. The top of R3 is best
      for craniofacial hyperhidrosis.

PMID- 23560267
TI  - [Acute penetrating atherosclerotic ulcers in aortic arch: differential diagnosis
      of chest pain].
AB  - Penetrating atherosclerotic ulcers (PAU) represent a pathological phenomenon in
      which ulceration of atheromatous lesions of the aorta penetrates the internal
      elastic lamina, reaching the middle muscular layer. These ulcers are more common
      in the descending thoracic aorta, being rare in the ascending aorta. The
      differential diagnosis between PAU and other entities of acute aortic syndromes
      (AAS) becomes difficult. The diagnosis of this disease is made through imaging
      studies: multidetector computed tomography (MDCT), magnetic resonance (MR) or
      transesophageal echocardiography (TEE). After diagnosis, the PAU of the ascending
      aorta should be treated surgically in an emergency context. In this paper the
      authors report a case of PAU in the aortic arch in a 84 years old patient
      admitted to the emergency room for chest pain. In this context a review of the
      natural evolution of this entity is made, with emphasis on diagnostic imaging
      modalities used for its characterization as well as their treatment options.

PMID- 23560268
TI  - [Influence of the time of myocardial ischemia on the electrocardiographic
      conduction intervals after surgical correction of aortic valvular stenosis].
AB  - The development of conduction disturbances after aortic valve replacement is a
      well-known complication. Since during the surgical procedure it is necessary to
      use extracorporeal circulation, it is plausible that the degree of myocardial
      ischemia (secondary to clamping of the aorta) contributes to the increase of the
      electrocardiographic conduction intervals. AIM: To understand if the time of
      myocardial ischemia performed at the surgical correction of valvular aortic
      stenosis is associated with increased post-operatory electrocardiographic PR, QRS
      and QT intervals. MATERIAL AND METHODS: 120 individuals were consecutively and
      retrospectively studied who exclusively underwent aortic valve replacement for
      aortic valve stenosis, between 2008 and 2010, at Centro Hospitalar de Vila Nova
      de Gaia/Espinho. Of the various parameters collected, were analysed the time of
      myocardial ischemia and electrocardiographic PR, QRS and QT corrected for heart
      rate intervals, at the time of admission and before hospital discharge. Then the
      value of the difference (variation) between the intervals after and before
      surgery was calculated. RESULTS: In the sample studied (age 72 +/- 10 years, TIM
      58 +/- 16 minutes), there is insufficient statistical evidence to state that the
      myocardial ischemia time and the variation of the PR (p=0,108), QRS (p=0,065) and
      QT corrected for heart rate (p=0,799) are related. CONCLUSIONS: The duration of
      myocardial ischemia does not influence the electrocardiographic intervals after
      surgical correction of aortic valve stenosis. However, after surgical
      intervention, there is an increase in PR and QRS intervals.

PMID- 23560269
TI  - [Ecodoppler evaluation on the progress of atherosclerotic disease in patients
      undergoing contralateral carotid endarterectomy].
AB  - PURPOSE: The clinical utility of monitoring by Doppler ultrasound patients
      undergoing carotid endarterectomy is not clearly established. Our goal is to
      evaluate by echo-Doppler the progress of contralateral stenosis in a real
      environment, in order to assess its usefulness. MATERIAL AND METHODS:
      Retrospective study with Doppler ultrasound monitoring in patients undergoing
      carotid endarterectomy for a period of 3 years. We included cases with Doppler
      echography before and at least one post-surgery. We excluded patients with
      contralateral thrombosis, contralateral stenosis, established surgical indication
      or prior carotid surgery. Analysis was performed using Kaplan-Meier curves to
      estimate the rate of patients free of progression and / or surgery, as well as an
      analysis of risk factors for progression of contralateral stenosis. RESULTS: We
      included 119 patients (41.2% symptomatic) age 68.3 +/- 8.41 years. The follow-up
      was 40.5 +/- 23.2 months, with a mean of 2.64 +/- 1.58 scans per patient. The
      likelihood of progression of contralateral carotid stenosis was estimated at 91,
      86, 81 and 79% at one, two, three and four years respectively. The only
      significant risk factor for progression was the presence of moderate or greater
      contralateral stenosis (30% or more) at the time of surgery. CONCLUSIONS: The
      evolution of the contralateral carotid atherosclerosis is relatively common. The
      degree of stenosis correlates with early progression, the study by echo-Doppler
      plays an important role in monitoring these patients.

PMID- 23560270
TI  - [Sequential surgical treatment of multiple primary infectious aneurysms of the
      thoracic and abdominal aorta].
AB  - A 26-year-old woman, complained of repeated urinary infections at the beginning
      of February 2010. Several urine sample tests identified an Escherichia colli
      strain, which was treated with antibiotics, according to the antibiogram data.
      Shortly afterwards, as a result of a back pain, a pyelonephritis was diagnosed,
      which was also treated with antibiotics. The pain progressively intensified over
      time and in June 2011 she began to suffer from high and persistent fever, which
      led to her hospitalisation. The investigation through CT-angiography showed the
      existence of three aneurysms of the thoracic aorta (one of the aortic arch and
      two of the descending thoracic aorta) and a large aneurysm of the abdominal
      aorta, in a contained rupture, surrounding the origin of the renal arteries, of
      infectious etiology. The patient underwent three sequential and successful
      surgical operations, using the conventional approach that consisted in the
      resection and replacement of the aneurysms with "in situ" vascular prosthesis.
      The main aspects of the pathology, clinical presentation and treatment of this
      extensive, rare and challenging situation are presented and discussed herein.

PMID- 23560271
TI  - [Acute occlusion of a popliteal aneurysm - the value of intra-arterial
      preoperative thrombolysis].
AB  - In this paper it is presented a clinical report on intra-arterial thrombolysis of
      an acute thrombosed popliteal artery aneurysm. We report the technical aspects
      and discuss indications, principal advantages and contraindications of this form
      of treatment.

PMID- 23560272
TI  - [Surgical management of a dissecting aneurysm of the thoracic aorta in a patient
      with Marfan's syndrome - case report].
AB  - Marfan's Syndrome is a rare connective tissue disease whose surgical treatment
      presents several challenges. The existing criteria and recommendations on how and
      when to surgically approach this disease is almost exclusively confined to the
      root and ascending aorta, in contrast to the variability of indications on the
      involvement of the remaining segments of the thoracic and abdominal aorta, due to
      the multiplicity, morphology and topography of these involvements. This case
      report is related to a 39 year old woman with Marfan's syndrome, with a type B
      chronic dissection and a segmentar aneurysm of the proximal descending thoracic
      aorta with 6,1cm of maximum diameter. The clinical and imagiologic evaluation
      pointed out the absence of any disorder of the heart, root or ascending aorta.
      The patient underwent surgical management of the dissecting aneurysm through a
      transthoracic approach to the aneurysm, with fenestration of the distal aorta and
      exclusion of the aneurism and intercostal arteries. The efficacy and result of
      the procedure in addition to the rarity of the vascular pathology presented by
      the patient, even in the context of a Marfan, completely justify the presentation
      and disclosure of this clinical case.

PMID- 23560273
TI  - [Radiofrequency-powered segmental thermal ablation in chronic venous disorders: A
      single center experience].
AB  - BACKGROUND: In the last decade, endovascular radiofrequency obliteration has been
      used as a safe and feasible method, alternative to conventional vein-stripping
      surgery. METHODS: Data were collected from our center between January 2009 and
      June 2011. Pretreatment examination included lower limb assessment using CEAP
      classification and VCSS (Vein Clinical Severity Score). Ultrasound examination
      was performed at first follow-up visit (one week to one month after surgery) and
      the last-one in September 2011. RESULTS: The study enrolled 30 patients (33
      legs), their mean age was 41.4 +/- 10.4 and 76,7% (n=23) were female. Mean follow
      up time was 240 days. Treated veins included 32 great saphenous vein above-knee
      segments, and one small saphenous vein. Only 8% of patients were free of pain
      before treatment and at last follow-up 61% reported no pain. Edema rate also
      improved from 52% (before surgery) to 9% at last control. During follow-up, two
      treated vessels were identified as patent, albeit competent: one a small
      saphenous vein and the other a segment of a great saphenous vein. Two cases of
      paresthesias and one of hyperpigmentation were observed at stab avulsion site.
      The mean VCSS score was 5,6 +/-3.11before surgery and 1,4+/-1.34 at last follow
      up. CONCLUSION: Radiofrequency segmental thermal ablation effectively reduced
      symptoms of venous insufficiency, with a significant reduction at VCSS score, and
      was a well tolerated and safe method, with few complications.

PMID- 23560274
TI  - [Pseudoaneurysm of the right common iliac artery in a case of Behcet's disease.
      Surgical management].

PMID- 23560275
TI  - Spectral cytopathology: new aspects of data collection, manipulation and
      confounding effects.
AB  - This paper presents a short review on the improvements in data processing for
      spectral cytopathology, the diagnostic method developed for large scale
      diagnostic analysis of spectral data of individual dried and fixed cells. This
      review is followed by the analysis of the confounding effects introduced by
      utilizing reflecting "low-emissivity" (low-e) slides as sample substrates in
      infrared micro-spectroscopy of biological samples such as individual dried cells
      or tissue sections. The artifact introduced by these substrates, referred to as
      the "standing electromagnetic wave" artifact, indeed, distorts the spectra
      noticeably, as postulated recently by several research groups. An analysis of the
      standing wave effect reveals that careful data pre-processing can reduce the
      spurious effects to a level where they are not creating a major problem for
      spectral cytopathology and spectral histopathology.

PMID- 23560276
TI  - Construction of right-handed-, left-handed-, and racemic helical coordination
      polymers. Enantioselective recognition using chiral helical crystals.
AB  - Infinite square-tubular helices, [CuCl2(L)(S)] (L = bis(4
      pyridyl)methylvinylsilane; S = Me2SO, HCONMe2), were constructed. This helical
      system affords three kinds of P, M crystals in Me2SO, and racemic crystals in
      HCONMe2. The cyclic voltammogram (CV) technique using the M-crystals is an
      effective tool for discerning the chirality of proline.

PMID- 23560277
TI  - Covalent organic polymer supported palladium catalysts for CO oxidation.
AB  - Covalent organic polymer-4 (COP-4) supported palladium (Pd) catalysts were
      prepared for the first time. The Pd particles are highly dispersed into pores of
      COP-4 with electron reduction and the use of N,N-dimethylformamide (DMF) as the
      solvent. The catalysts show high activity for CO oxidation.

PMID- 23560278
TI  - Pathophysiology of migraine.

PMID- 23560279
TI  - Headache toolbox:chronic migraine.

PMID- 23560281
TI  - Parathyroidectomy, elevated depression scores, and suicidal ideation in patients
      with primary hyperparathyroidism: results of a prospective multicenter study.
AB  - OBJECTIVE: To assess anxiety and depression symptoms, suicidal ideation, and
      health-related quality of life (HRQOL) in a large series of consecutive patients
      with primary hyperparathyroidism (pHPT) before and after parathyroidectomy.
      DESIGN: This prospective multicenter study investigated preoperative and
      postoperative depression, anxiety, suicidal ideation, and HRQOL in patients with
      pHPT and compared these variables with a control group with nontoxic thyroid
      nodules. PATIENTS: The study included 194 patients with pHPT and 186 control
      subjects. MAIN OUTCOME MEASURES: Depression was evaluated with the Hospital
      Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9, which
      also assessed suicidal ideation. Anxiety was evaluated with the HADS. Health
      related quality of life was measured with the 36-Item Short Form survey. RESULTS:
      Parathyroidectomy achieved a 98% cure rate. Preoperatively, severe depression
      (HADS score >= 11) was seen in 20% of the pHPT group and 9% of the control group.
      The Patient Health Questionnaire-9 detected moderate to severe depression in 17%
      of the patients with pHPT and 7% of the control subjects. Patients with pHPT had
      higher HADS anxiety scores (mean, 7.7) than control subjects (P < .01) or the
      German normative sample (P < .001). Compared with control subjects, patients with
      pHPT had significantly lower 36-Item Short Form survey preoperative physical and
      mental health summary scores (42.7 vs 49.5 and 41.2 vs 46.8, respectively; P =
      .001 for both comparisons). At 12 months follow-up, depression and anxiety
      decreased significantly in patients with pHPT; the prevalence of suicidal
      ideation was more than halved from the baseline (10.7% vs 22%; P = .008). Both
      physical and mental health scores (45.7 and 47.7, respectively) improved in
      patients with pHPT (P < .001 each) but not in control subjects. CONCLUSIONS:
      Depression, anxiety, and decreased HRQOL appear to be related to pHPT. Successful
      parathyroidectomy seems to reduce psychopathologic symptoms and improve HRQOL in
      this setting.

PMID- 23560282
TI  - Definitive surgical treatment of enterocutaneous fistula: outcomes of a 23-year
      experience.
AB  - OBJECTIVE: To analyze postoperative outcomes, morbidity, and mortality following
      enterocutaneous fistula (ECF) takedown. DESIGN, SETTING, AND PATIENTS:
      Retrospective review of the complete medical records of patients who presented to
      a single tertiary care referral center from December 24, 1987, to June 18, 2010,
      and subsequently underwent definitive surgical treatment for ECF originating from
      the stomach, small bowel, colon, or rectum. MAIN OUTCOME MEASURES: Postoperative
      fistula recurrence and mortality. RESULTS: A total of 153 patients received
      operative intervention for ECF. Most ECFs were referred to us from outside
      institutions (75.2%), high output (52.3%), originating from the small bowel
      (88.2%), and iatrogenic in cause (66.7%). Successful ECF closure was ultimately
      achieved in 128 patients (83.7%). Six patients (3.9%) died within 30 days of
      surgery, and overall 1-year mortality was 15.0%. Postoperative complications
      occurred in 134 patients, for an overall morbidity rate of 87.6%. Significant
      risk factors for fistula recurrence were numerous, but postoperative ventilation
      for longer than 48 hours, organ space surgical site infection, and blood
      transfusion within 72 hours of surgery carried the most considerable impact
      (relative risks, 4.87, 4.07, and 3.91, respectively; P < .05). Risk of 1-year
      mortality was also associated with multiple risk factors, the most substantial of
      which were postoperative pulmonary and infectious complications. Closure of
      abdominal fascia was protective against both recurrent ECF and mortality
      (relative risks, 0.47 and 0.38, respectively; P < .05). CONCLUSIONS:
      Understanding risk factors both associated with and protective against ECF
      recurrence and postoperative morbidity and mortality is imperative for
      appropriate ECF management. Closure of abdominal fascia is of utmost importance,
      and preventing postoperative complications must be prioritized to optimize
      patient outcomes.

PMID- 23560284
TI  - Risk of major nonemergent inpatient general surgical procedures in patients on
      long-term dialysis.
AB  - HYPOTHESIS: Patients on long-term dialysis undergoing major nonemergent general
      surgical procedures are thought to have high rates of postoperative complications
      and death. DESIGN: Retrospective cohort study. SETTING: Academic and private
      hospitals. PATIENTS: The American College of Surgeons National Surgical Quality
      Improvement Program database was used to select dialysis and nondialysis patients
      who had undergone nonemergent major general surgical procedures between 2005 and
      2008. Multivariable logistic regression analysis was used to examine the effect
      of dialysis on 30-day surgical outcomes adjusted for age, race, sex, work
      relative value units, American Society of Anesthesiologists class, and recent
      operations (within the past 30 days). MAIN OUTCOME MEASURES: Patient morbidity,
      mortality, and failure-to-rescue rates. RESULTS: Dialysis patients undergoing
      major nonemergent general surgical procedures were significantly more likely to
      develop pneumonia, unplanned intubation, ventilator dependence, and need for a
      reoperation within 30 days from the index procedure. Dialysis patients also had a
      higher risk of vascular complications and postoperative death. Older dialysis
      patients (aged >= 65 years) had a significantly higher postoperative mortality
      rate compared with their younger counterparts. Dialysis patients were
      significantly more likely to die after any complication occurred, and mortality
      rates were especially high following stroke, myocardial infarction, and
      reintubation. Abnormalities in potentially modifiable preoperative variables
      (blood urea nitrogen level, albumin level, and hematocrit) did not increase the
      risk of postoperative complications or death in dialysis patients compared with
      nondialysis patients. CONCLUSIONS: Dialysis patients undergoing nonemergent
      general surgery have significantly elevated risks of postoperative complications
      and death, particularly if they are aged 65 years or older.

PMID- 23560285
TI  - Substance use following bariatric weight loss surgery.
AB  - OBJECTIVE: To assess substance use before and after bariatric weight loss surgery
      (WLS). There is a paucity of research investigating the occurrence of substance
      use following bariatric WLS. It was hypothesized that patients who underwent WLS
      would exhibit an increase in substance use (drug use, alcohol use, and cigarette
      smoking) following surgery to compensate for a marked decrease in food intake.
      DESIGN: Prospective study. SETTING: A major urban community hospital.
      PARTICIPANTS: A total of 155 participants (132 women and 23 men) who underwent
      WLS were recruited from a preoperative information session at a bariatric surgery
      center. INTERVENTION: Participants received either laparoscopic Roux-en-Y gastric
      bypass surgery (n = 100) or laparoscopic adjustable gastric band surgery (n =
      55). Participants completed questionnaires to assess eating behaviors and
      substance use at preoperative baseline and 1, 3, 6, 12, and 24 months after
      surgery. MAIN OUTCOME MEASURE: Substance use as assessed by the Compulsive
      Behaviors Questionnaire. RESULTS: Participants reported significant increases in
      the frequency of substance use (a composite of drug use, alcohol use, and
      cigarette smoking, hereafter referred to as composite substance use) 24 months
      after surgery. Specifically, participants experienced a significant increase in
      the frequency of composite substance use from baseline to 24 months after surgery
      (P = .02), as well as significant increases from 1 month, 3 months, and 6 months
      to 24 months after surgery (all P <= .002). In addition, participants who
      underwent laparoscopic Roux-en-Y gastric bypass surgery reported a significant
      increase in the frequency of alcohol use from baseline to 24 months after surgery
      (P = .011). The response rate to the survey was 61% at 1-month follow-up, 41% at
      3-month follow-up, 43% at 6-month follow-up, 49% at 12-month follow-up, and 24%
      at 24-month follow-up. CONCLUSIONS: Patients may be at increased risk for
      substance use following bariatric WLS. In particular, patients who undergo
      laparoscopic Roux-en-Y gastric bypass surgery may be at increased risk for
      alcohol use following WLS. Our study is among the first to document significant
      increases in substance use following WLS using longitudinal data.

PMID- 23560286
TI  - The time has come to redefine the classic symptoms of primary
      hyperparathyroidism: comment on "parathyroidectomy, elevated depression scores,
      and suicidal ideation in patients with primary hyperparathyroidism".

PMID- 23560283
TI  - The prospective, observational, multicenter, major trauma transfusion (PROMMTT)
      study: comparative effectiveness of a time-varying treatment with competing
      risks.
AB  - OBJECTIVE: To relate in-hospital mortality to early transfusion of plasma and/or
      platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC
      ratios. DESIGN: Prospective cohort study documenting the timing of transfusions
      during active resuscitation and patient outcomes. Data were analyzed using time
      dependent proportional hazards models. SETTING: Ten US level I trauma centers.
      PATIENTS: Adult trauma patients surviving for 30 minutes after admission who
      received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n
      = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or
      platelets) within 24 hours (n = 905, the analysis group). MAIN OUTCOME MEASURE:
      In-hospital mortality. RESULTS: Plasma:RBC and platelet:RBC ratios were not
      constant during the first 24 hours (P < .001 for both). In a multivariable time
      dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio =
      0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95%
      CI, 0.31-0.98) were independently associated with decreased 6-hour mortality,
      when hemorrhagic death predominated. In the first 6 hours, patients with ratios
      less than 1:2 were 3 to 4 times more likely to die than patients with ratios of
      1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with
      mortality, when competing risks from nonhemorrhagic causes prevailed.
      CONCLUSIONS: Higher plasma and platelet ratios early in resuscitation were
      associated with decreased mortality in patients who received transfusions of at
      least 3 units of blood products during the first 24 hours after admission. Among
      survivors at 24 hours, the subsequent risk of death by day 30 was not associated
      with plasma or platelet ratios.

PMID- 23560287
TI  - Elective surgery in dialysis patients: realistic risk information from the
      American College of Surgeons National Surgical Quality Improvement Program
      Database: comment on "risk of major nonemergent inpatient general surgical
      procedures in patients on long-term dialysis".

PMID- 23560288
TI  - [Antibiotic regimens in tuberculous meningitis].

PMID- 23560289
TI  - Special issue in honor of Jerome Cornfield on the centennial of his birth.

PMID- 23560290
TI  - Proceedings of the 1st Asian Congress of Biotechnology (ACB-2011), May 11-15,
      2011, Shanghai, China.

PMID- 23560292
TI  - Abstracts and proceedings of the 22nd International Congress on Thrombosis, 6 - 9
      October, 2012,Nice, France.

PMID- 23560291
TI  - Special issue dedicated to Dr. Atta-ur-Rahman on his 70th birthday.

PMID- 23560293
TI  - Special Collection of Papers in Honor of Dr. John K. Critser.

PMID- 23560294
TI  - Proceedings of the First International Conference on Organic Food Quality and
      Health Research, May, 2011, Prague, Czech Republic.

PMID- 23560295
TI  - Telaprevir-related dermatitis.
AB  - OBJECTIVE: To evaluate the incidence, type, and severity of telaprevir-associated
      skin reactions. DESIGN: Three dermatologists assessed available information
      including photographs, biopsy results, and clinical summaries of all cases with
      skin eruptions reported as moderate or severe during the telaprevir clinical
      development program. For cases from placebo-controlled trials, they were masked
      to exposure. SETTINGS: Phase 1 to 3 studies of telaprevir combination therapy for
      hepatitis C. PATIENTS: All patients with skin eruptions enrolled in telaprevir
      clinical trials prior to 2011 MAIN OUTCOME MEASURES: Incidence, diagnosis,
      morphologic features, extent, and severity of skin eruption. RESULTS: Skin
      eruptions were more frequent in patients who received telaprevir as part of
      hepatitis C treatment compared with pegylated interferon (peginterferon) and
      ribavirin alone (56% vs 34% overall; 3.7% vs 0.4% severe). Occurring at any time
      during the 12 weeks of telaprevir combination regimen, in more than 90% of cases,
      this eruption is pruritic eczematous dermatitis. None of the clinical or genetic
      factors examined were substantial risk factors for dermatitis. Three cases of
      Stevens-Johnson Syndrome (SJS), and 11 cases of Drug Reaction with Eosinophilia
      and Systemic Symptoms (DRESS) were suspected, with 2 SJS and 3 DRESS cases
      considered likely. CONCLUSIONS: Telaprevir-related dermatitis occurs in a
      majority of telaprevir-treated patients. It is an eczematous dermatitis that
      differs in timing and appearance from the eruptions usually associated with drug
      reactions. The strong signal for an increased risk of DRESS or SJS requires
      particular vigilance in telaprevir-treated patients.

PMID- 23560296
TI  - Association between vitiligo extent and distribution and quality-of-life
      impairment.
AB  - OBJECTIVE: To determine whether the extent, distribution, and duration of
      vitiligo are associated with impairment of specific aspects of quality of life.
      DESIGN: A prospective questionnaire-based study of 1541 adults with vitiligo.
      SETTING: Online questionnaire. MAIN OUTCOME MEASURES: Affected body surface area
      (BSA), distribution and duration of vitiligo, associated symptoms, and quality of
      life using the Dermatology Life Quality Index (DLQI). RESULTS: Vitiligo had a
      negative effect on numerous aspects and the total score of the DLQI (mean [SD],
      5.9 [5.5]). The DLQI scores in vitiligo were associated with an affected BSA of
      more than 25% (ordinal logistic regression; adjusted odds ratio, 2.17 [95% CI,
      1.71-2.75; P<.001]) and number of body parts affected with vitiligo (P<=.009) but
      not laterality (P=.06) or duration of disease (P>=.54). Itching and/or burning
      skin occurred in a sizable percentage of vitiligo patients (35.1%) and were
      predicted by an affected BSA of more than 25% (adjusted odds ratio, 1.59 [95% CI,
      1.26-2.01; P<.001]). Sexual dysfunction occurred in 18% of patients and was
      predicted by an affected BSA of more than 25% (adjusted odds ratio, 1.94 [95% CI,
      1.44-2.61; P<.001]) and vitiligo lesions in the genital area (1.82 [1.30-2.53;
      P<.001]). CONCLUSIONS: Vitiligo extent is associated with increased quality-of
      life impairment, including itching and sexual dysfunction. Moreover, different
      distributions of vitiligo lesions are associated with impairment of different
      aspects of quality of life. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01401374

PMID- 23560298
TI  - CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell
      carcinoma.
AB  - OBJECTIVE: To characterize the presence of CD200 and CD200 receptor (CD200R) in
      the human cutaneous squamous cell carcinoma (SCC) microenvironment and to define
      a possible role for the CD200 axis in immune evasion by SCC. DESIGN: Gene
      expression in SCC vs normal skin was studied. Laser capture microdissection was
      used to determine differential expression of CD200 in normal skin vs actinic
      keratosis vs SCC in situ vs invasive SCC. Immunofluorescence microscopy was used
      to define expression of CD200R on macrophages, myeloid dendritic cells, natural
      killer cells, and T cells in SCC vs normal skin. The effects of SCC supernatant
      on induction of CD200 in human blood endothelial cells was also examined.
      SETTING: Academic Medical Center with an established Section of Mohs and
      Dermatologic Surgery and an active Cutaneous Biology Research Program.
      PARTICIPANTS: Surgical discard tissue from deidentified patients and samples of
      normal skin from healthy volunteers were used in this study. MAIN OUTCOME
      MEASURES: Expression of CD200 on SCC-associated blood vessels; expression of
      CD200 receptor on SCC-associated macrophages and T cells; and induction of CD200
      on endothelial cells by SCC supernatants. RESULTS: CD200 gene and message were
      upregulated in SCC stroma. Immunostaining revealed a higher number of CD200(+)
      cells in SCC stroma than in normal dermis (180.8 cells/mm(2) vs 24.6 cells/mm(2))
      (P<.01). CD200 was further identified mainly on blood vessel endothelium in SCC.
      Tumor supernatant was able to induce CD200 expression on human dermal blood
      endothelial cells in culture. CD200R was identified on macrophages and dendritic
      cells in SCC microenvironment. CONCLUSIONS: CD200 expression on local blood
      vessels may promote tumor progression by suppressing CD200R myeloid cells during
      diapedesis. These data highlight a previously unrecognized mechanism of immune
      evasion by SCC and may provide guidance for the development of targeted therapy.

PMID- 23560297
TI  - Association of pediatric psoriasis severity with excess and central adiposity: an
      international cross-sectional study.
AB  - OBJECTIVE: To investigate the relationship of excess and central adiposity with
      pediatric psoriasis severity. DESIGN, SETTING, AND PARTICIPANTS: Multicenter,
      cross-sectional study of 409 psoriatic children. Psoriasis was classified as mild
      (worst Physician's Global Assessment score <=3 with body surface area <=10%) or
      severe (worst Physician's Global Assessment score >=3 with body surface area
      >10%). Children were enrolled from 9 countries between June 19, 2009, and
      December 2, 2011. MAIN OUTCOME MEASURES: Excess adiposity (body mass index
      percentile) and central adiposity (waist circumference percentile and waist to
      height ratio). RESULTS: Excess adiposity (body mass index >=85th percentile)
      occurred in 37.9% of psoriatic children (n=155) vs 20.5% of controls (n=42) but
      did not differ significantly by severity. The odds ratio (95% CI) of obesity
      (body mass index >=95th percentile) overall in psoriatic children vs controls was
      4.29 (1.96-9.39) and was higher with severe (4.92; 2.20-10.99) than with mild
      (3.60; 1.56-8.30) psoriasis, particularly in the United States (7.60; 2.47-23.34,
      and 4.72; 1.43-15.56, respectively). Waist circumference above the 90th
      percentile occurred in 9.3% of the control (n=19), 14.0% of the mild psoriasis
      (n=27), and 21.2% of the of severe psoriasis (n=43) participants internationally;
      this incidence was highest in the United States (12.0% [n=13], 20.8% [16], and
      31.1% [32], respectively). Waist to height ratio was significantly higher in
      psoriatic (0.48) vs control (0.46) children but was unaffected by psoriasis
      severity. Children with severe psoriasis at its worst, but mild at enrollment,
      showed no significant difference in excess or central adiposity from children
      whose psoriasis remained severe. CONCLUSIONS: Globally, children with psoriasis
      have excess adiposity and increased central adiposity regardless of psoriasis
      severity. The increased metabolic risks associated with excess and central
      adiposity warrant early monitoring and lifestyle modification. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00879944

PMID- 23560299
TI  - Chlorhexidine gluconate-impregnated central access catheter dressings as a cause
      of erosive contact dermatitis: a report of 7 cases.
AB  - BACKGROUND: Chlorhexidine gluconate-impregnated dressings have become widely
      adopted as a means to reduce the risk for catheter-associated bloodstream
      infections. These dressings release antiseptic under occlusion onto the skin
      surrounding catheter insertion sites. Although chlorhexidine gluconate is a known
      cause of contact dermatitis, the phenotypic range of this adverse effect of
      chlorhexidine gluconate-impregnated dressings in critically ill patients has not
      been described. OBSERVATIONS: We report 7 cases of erosive irritant contact
      dermatitis due to chlorhexidine gluconate-impregnated transparent dressings. Six
      of these patients were children (age range, 4 months to 2 years); the adult was a
      critically ill 62-year-old man. Four patients were immunosuppressed after solid
      organ transplant and all were receiving blood pressure support at the time of
      this reaction. The insertion sites of femoral catheters were involved in all but
      1 case; 3 catheter sites were involved in the adult patient. Results of extensive
      infectious workups were negative. All lesions resolved with discontinuation of
      the chlorhexidine gluconate-containing dressings, local wound care, and
      alternative antimicrobial dressings. CONCLUSIONS: Erosive contact dermatitis is
      an under-recognized complication of chlorhexidine gluconate-impregnated
      dressings. Health care providers should be aware of this risk, particularly in
      young children and immunosuppressed and/or critically ill patients, who may be
      more susceptible to the irritant effects of these dressings. When the dressings
      are used, patients should be monitored closely for skin breakdown.

PMID- 23560300
TI  - Tandem repeat polymorphisms. Preface.

PMID- 23560301
TI  - Tandem repeat polymorphisms: Mediators of genetic plasticity, modulators of
      biological diversity and dynamic sources of disease susceptibility.
AB  - Tandem repetitive DNA elements (tandem repeats), including microsatellites and
      simple sequence repeats, are extremely common throughout the genomes of a wide
      range of species. Tandem repeat expansions have been found to cause a range of
      monogenic diseases, such as Huntington's disease, various ataxias and other
      neurological diseases. The human genome contains hundreds ofthousands of distinct
      tandem repeats, many of which appear to have evolved to regulate specific aspects
      of gene expression, RNA function and protein function. Tandem repeat
      polymorphisms (TRPs) provide a unique source of genetic variability that has an
      extended digital distribution, as opposed to the usual binary nature of single
      nucleotide polymorphisms. In this chapter I will review studies in which tandem
      repeats have been implicated in a multitude of molecular and cellular processes
      associated with the development, behavior and evolution of a variety of animal
      species, including mammals. Recent data suggesting that these repetitive
      sequences can increase the 'evolvability' of genomes provides further evidence
      that TRPs not only have functional consequences but also provide a rich source of
      genetic diversity that can facilitate evolutionary processes. I propose that a
      readily mutable subclass of tandem repeats may provide an important template for
      stochastic genetic variation, which could in turn generate diversity in
      epigenetics, development and organismal function, thus impacting upon evolution.
      Furthermore, the distinctive characteristics ofTRPs also uniquely position them
      as contributors to complex polygenic disorders. Ultimately, there is much to be
      gained from systematic analysis of the 'repeatome', defined as the entire set of
      tandem repeats and other repetitive DNA in a genome, as well as their transcribed
      and translated expression products. Applying such approaches not only to the
      human genome but to other species will yield new insights into the genetic
      regulation of a wide range of biological processes in healthy and diseased
      states.

PMID- 23560302
TI  - Evolution of simple sequence repeats as mutable sites.
AB  - Because natural selection is commonly presumed to minimize mutation rates, the
      discovery of mutationally unstable simple sequence repeats (SSRs) in many
      functional genomic locations came as a surprise to many biologists. Whether such
      SSRs persist in spite of or because of their intrinsic mutability-whether they
      constitute a genetic burden or an evolutionary boon--remains uncertain. Two
      contrasting evolutionary explanations can be offered for SSR abundance. First,
      suppressing the inherent mutability of repetitive sequences might simply lie
      beyond the reach of natural selection. Alternatively, natural selection might
      indirectly favor SSRs at sites where particular repeat-number variants have
      provided positive contributions to fitness. Indirect selection could thereby
      shape SSRs into "tuning knobs" that facilitate evolutionary adaptation by
      implementing an implicit protocol of incremental adjustability. The latter
      possibility is consistent with deep evolutionary conservation of some SSRs,
      including several in genes with neurological and neurodevelopmental function.

PMID- 23560303
TI  - Single amino acid and trinucleotide repeats: function and evolution.
AB  - The most well known effect of single amino acid repeat expansion, beyond a
      certain threshold, is the development of a specific disease, depending on the
      protein in which the expansion has occurred. For example, the expansion of the
      glutamine repeat in huntingtin leads to the debilitating neurodegenerative
      disease, Huntington's disease. Similarly, there are a range of other disorders
      caused by trinucleotide repeat expansions encoding polyglutamine or polyalanine
      tracts. The age of onset of the polyglutamine-induced neurodegenerative diseases
      is usually negatively correlated with the length of expanded CAG/glutamine
      repeat. However, recent studies have given evidence that single amino acid
      repeats may also play critical roles in normal protein function and that changes
      in the length of single amino acid repeats is likely to play a beneficial role in
      evolution. This chapter will look at the prevalence, function and possible role
      single amino acid repeats have in evolution and other biological processes.

PMID- 23560304
TI  - Promoter microsatellites as modulators of human gene expression.
AB  - Microsatellites in and around genes have been shown to modulate levels of gene
      expression in multiple organisms, ranging from bacteria to humans. Here we will
      discuss promoter microsatellites known to modulate gene expression, with a few
      key examples related to the human brain. Many of the microsatellites we discuss
      are highly conserved in mammals, indicating that selection may favor their
      retention as "tuning knobs" of gene expression. We will also discuss the
      mechanisms by which microsatellites in promoters can alter gene expression as
      they expand and contract, with particular attention to secondary structures like
      Z-DNA and H-DNA. We suggest that promoter microsatellites, especially those that
      are highly conserved, may be an important source of human phenotypic variation.

PMID- 23560305
TI  - Dynamic mutations: where are they now?
AB  - Dynamic mutations are those caused by the expansion of existing polymorphic DNA
      repeat sequences beyond a copy number threshold. These genetic mutations can give
      rise to dominant, recessive or X-linked disorders, dependent upon the location of
      the repeat sequence with respect to the genes that are affected by the expansion.
      The distinguishing feature of these mutations is their instability, which is a
      function of the copy number of repeats and can occur in either meiosis or
      mitosis. For some of the resultant disorders there is a relationship between
      repeat copy number and age-at-onset and/or severity ofsymptoms ofthe disease. For
      this reason much effort is now focused on identifying the pathogenic pathways
      from the mutation to the disease symptoms in the hope of finding means of
      delaying onset, slowing progression or even preventing symptoms ofthe disease.
      The growing list ofneurodegenerative and neuromuscular diseases caused by dynamic
      mutations includes Huntington's disease (HD), spinobulbar muscular atrophy
      (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA), a number of spinocerebellar
      ataxias (SCAs), oculopharyngeal muscular dystrophy (OPMD), myotonic dystrophy
      Type 1 and 2 (DM1 and 2), Huntington's disease-like 2 (HDL-2), Friedrich's ataxia
      (FRDA), Fragile X associated tremor ataxia syndrome (FXTAS), Fragile XE (FRAXE)
      and Fragile XA (FRAXA). This chapter aims to give a brief overview of what is
      currently known about each disease and the mechanisms underlying pathogenesis.

PMID- 23560307
TI  - Molecular pathways to polyglutamine aggregation.
AB  - Over 100 human cellular proteins contain a repetitive polyglutamine tract,
      however, only nine ofthese proteins are associated with disease. In these
      proteins, the expanded polyQ tract perturbs the native conformation, resulting in
      an ordered aggregation process that leads to the formation of amyloid-like
      fibrils. The misfolding pathway involves the formation of prefibrillar oligomeric
      structures, which are proposed to be involved in cellular toxicity. Non-polyQ
      host protein regions modulate the misfolding pathway, suggesting an importance
      ofprotein context in aggregation. This chapter describes the current research
      regarding polyQ misfolding, with emphasis on the species populated during
      aggregation, suggesting an important role of protein context in modulating the
      aggregation pathway.

PMID- 23560308
TI  - Polyglutamine aggregation in Huntington and related diseases.
AB  - Polyglutamine (polyQ)-expansions in different proteins cause nine
      neurodegenerative diseases. While polyQ aggregation is a key pathological
      hallmark of these diseases, how aggregation relates to pathogenesis remains
      contentious. In this chapter, we review what is known about the aggregation
      process and how cells respond and interact with the polyQ-expanded proteins. We
      cover detailed biophysical and structural studies to uncover the intrinsic
      features of polyQ aggregates and concomitant effects in the cellular environment.
      We also examine the functional consequences ofpolyQ aggregation and how cells may
      attempt to intervene and guide the aggregation process.

PMID- 23560309
TI  - Selective neurodegeneration, neuropathology and symptom profiles in Huntington's
      disease.
AB  - Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative
      disease caused by a CAG repeat expansion in exon 1 of the Huntington gene (HD)
      also known as IT15. Despite the disease being caused by dysfunction ofa single
      gene, expressed as an expanded polyglutamine in the huntingtin protein, there is
      a major variability in the symptom profile of patients with Huntington's disease
      as well as great variability in the neuropathology. The symptoms vary throughout
      the course of the disease and vary greatly between cases. These symptoms present
      as varying degrees of involuntary movements, mood, personality changes, cognitive
      changes and dementia. To determine whether there is a morphological basis for
      this symptom variability, recent studies have investigated the cellular and
      neurochemical changes in the striatum and cerebral cortex in the human brain to
      determine whether there is a link between the pathology in these regions and the
      symptomatology shown by individual cases. These studies together revealed that
      cases showing mainly mood symptom profiles correlated with marked degeneration in
      the striosomal compartment of the striatum, or in the anterior cingulate gyrus of
      the cerebral cortex. In contrast, in cases with mainly motor symptoms
      neurodegeneration was especially marked in the primary motor cortex with variable
      degeneration in both the striosomes and matrix compartments of the striatum.
      These studies suggest that the variable degeneration of the striatum and cerebral
      cortex correlates with the variable profiles of Huntington's disease.

PMID- 23560310
TI  - Kennedy's disease: clinical significance of tandem repeats in the androgen
      receptor.
AB  - Kennedy's disease (KD) or spinobulbar muscular atrophy is a hereditary X-linked,
      progressive neurodegenerative condition caused by an expansion of the CAG triplet
      repeat in the first exon of the androgen receptor gene. The phenotype in its full
      form is only expressed in males and presents as weakness and wasting of the upper
      and lower limbs and bulbar muscles associated with absent reflexes. Sensory
      disturbances are present. Various endocrine abnormalities including decreased
      fertility and gynecomastia are common and amongst the first features of KD.
      Animal models of KD have demonstrated improvement on withdrawal of testosterone,
      indicating that this agonist of the androgen receptor is required for the toxic
      effect. Potential therapies based on testosterone withdrawal in humans have shown
      some promise, but efficacy remains to be proven. Potential clinical factors,
      pathogenesis and future approaches to therapy are reviewed in this chapter.

PMID- 23560311
TI  - Characterising the neuropathology and neurobehavioural phenotype in Friedreich
      ataxia: a systematic review.
AB  - Friedreich ataxia (FRDA), the most common of the hereditary ataxias, is an
      autosomal recessive, multisystem disorder characterised by progressive ataxia,
      sensory symptoms, weakness, scoliosis and cardiomyopathy. FRDA is caused by a GAA
      expansion in intron one of the FXN gene, leading to reduced levels of the encoded
      protein frataxin, which is thought to regulate cellular iron homeostasis. The
      cerebellar and spinocerebellar dysfunction seen in FRDA has known effects on
      motor function; however until recently slowed information processing has been the
      main feature consistently reported by the limited studies addressing cognitive
      function in FRDA. This chapter will systematically review the current literature
      regarding the neuropathological and neurobehavioural phenotype associated with
      FRDA. It will evaluate more recent evidence adopting systematic experimental
      methodologies that postulate that the neurobehavioural phenotype associated with
      FRDA is likely to involve impairment in cerebello-cortico connectivity.

PMID- 23560312
TI  - Polyalanine tract disorders and neurocognitive phenotypes.
AB  - Expansion of polyalanine tracts cause at least 9 inherited human diseases. Eight
      of these nine diseases are due to expansions in transcription factors and give
      rise to congenital disorders, many with neurocognitive phenotypes. Disease
      causing expansions vary in length dependingupon the gene in question, with the
      severity of the associated clinical phenotype generally increasing with length of
      the polyalanine tract. The past decade has seen considerable progress in the
      understanding on how these mutations may arise and the functional effect of
      expanded polyalanine tracts on the resulting protein. Despite this progress, the
      pathogenic mechanism of expanded polyalanine tracts contributing to the
      associated disease states remains poorly understood. Gaining insights into the
      mechanisms that underlie the pathogenesis of different expanded polyalanine tract
      mutations will be a necessary step on the path to the design of potential
      treatment strategies for the associated diseases.

PMID- 23560313
TI  - Time to reflect and look ahead to new challenges.

PMID- 23560314
TI  - Survivorship: the need to assess the effects of an altered life.

PMID- 23560315
TI  - Improving pain assessment for patients with cognitive impairment: development of
      a pain assessment toolkit.
AB  - A significant number of people experience pain and cognitive impairment toward
      the end of life. Assessment of their pain becomes more complex as their cognitive
      abilities diminish and they lose their ability to express themselves and
      understand their experience of pain. The rate and pattern of cognitive decline
      differs between individuals, which makes it difficult to take a standardised
      approach to pain assessment. Based on a review of the literature, this article
      describes the development of a pain assessment toolkit consisting of guidelines
      and a selection of self-report and behavioural assessment tools to support health
      professionals in tailoring their assessment to meet the needs of an individual
      with cognitive impairment.

PMID- 23560306
TI  - Unstable mutations in the FMR1 gene and the phenotypes.
AB  - Fragile X syndrome (FXS), a severe neurodevelopmental anomaly, and one of the
      earliest disorders linked to an unstable ('dynamic') mutation, is caused by the
      large (>200) CGG repeat expansions in the noncoding portion of the FMR1 (Fragile
      X Mental Retardation-1) gene. These expansions, termed full mutations, normally
      silence this gene's promoter through methylation, leading to a gross deficit of
      the Fragile X Mental Retardation Protein (FMRP) that is essential for normal
      brain development. Rare individuals with the expansion but with an unmethylated
      promoter (and thus, FMRP production), present a much less severe form of FXS.
      However, a unique feature of the relationship between the different sizes of CGG
      expanded tract and phenotypic changes is that smaller expansions (<200) generate
      a series of different clinical manifestations and/or neuropsychological changes.
      The major part of this chapter is devoted to those FMR1 alleles with small (55
      200) CGG expansions, termed 'premutations', which have the potential for
      generating the full mutation alleles on mother-offspring transmission, on the one
      hand, and are associated with some phenotypic changes, on the other. Thus, the
      role of several factors known to determine the rate of CGG expansion in the
      premutation alleles is discussed first. Then, an account ofvarious
      neurodevelopmental, cognitive, behavioural and physical changes reported in
      carriers of these small expansions is given, and possible association of these
      conditions with a toxicity of the elevated FMR1 gene's transcript (mRNA) is
      discussed. The next two sections are devoted to major and well defined clinical
      conditions associatedwith the premutation alleles. The first one is the late
      onsetneurodegenerative disorder termed fragile X-associated tremor ataxia
      syndrome (FXTAS). The wide range of clinical and neuropsychological
      manifestations of this syndrome, and their relevance to elevated levels of the
      FMR1 mRNA, are described. Another distinct disorder linked to the CGG repeat
      expansions within the premutation range is fragile X-associated primary ovarian
      insufficiency (FXPOI) in females, and an account of the spectrum of
      manifestations of this disorder, together with the latest findings suggesting an
      early onset of the ovarian changes, is given. In the following section, the most
      recent findings concerning the possible contribution of FMR1 'grey zone' alleles
      (those with the smallest repeat expansions overlapping withthenormal rangei.e.,41
      54CGGs), tothepsychologicalandclinical manifestations, already associated with
      premutation alleles, are discussed. Special emphasis has been placed on the
      possibility that the modest elevation of 'toxic' FMR1 mRNA in the carriers of
      grey zone alleles may present an additional risk for some neurodegenerative
      diseases, such as those associated with parkinsonism, by synergizing with either
      other susceptibility genes or environmental poisons. The present status ofthe
      treatment of fragile X-related disorders, especially FXS, is presented in the
      last section of this chapter. Pharmacological interventions in this syndrome have
      recently extended beyond stimulants and antipsychotic medications, and the latest
      trials involving a group of GluR5 antagonists aim to ascertain if these
      substances have the potential to reverse some of the neurobiological
      abnormalities of FXS.

PMID- 23560316
TI  - Anger: a common form of psychological distress among patients at the end of life.
AB  - Psychological distress is common in palliative care patients and their families,
      and anger is a complex component of distress experienced by many patients at the
      end of life. Anger can be a form of tension release, as well as a coping
      mechanism for the patient and a way to disguise fear and anxiety. The
      interdisciplinary team are responsible for recognising psychological distress in
      patients, assessing their needs, and providing adequate psychological support.
      Although a certain level of psychological distress such as anger is expected in
      terminally ill patients owing to their situation, such responses may also be
      dysfunctional. This paper aims to highlight the challenges and complexities of
      adequately assessing and supporting palliative care patients who are presenting
      with psychological distress in the form of anger, in order to relieve their
      suffering and assist them in resolving their issues and improving their quality
      of life. Anger can be difficult to treat, and for some patients can be more
      distressing than some physical symptoms. Hence this paper also aims to offer
      anger management guidance to palliative care practitioners.

PMID- 23560317
TI  - Spanish nurses' preparedness to care for hospitalised terminally ill patients and
      their daily approach to caring.
AB  - OBJECTIVE: To describe Spanish nurses' preparedness to care for hospitalised
      terminally ill patients and how this translates into care delivery. METHODS: An
      exploratory, sequential mixed methods study with two stages. Stage I used
      unstructured observations of 22 hospital nurses over 235 hours to understand
      their daily reality, followed by semi-structured interviews with 21 nurses to
      elicit their perspectives. Stage 2 was a regional survey (65% response rate)
      concerned with hospital nurses' opinions of caring for terminally ill patients
      and their perceived competence. RESULTS: The nurses felt competent to provide
      physical but not emotional care for terminally ill patients. They reported that
      care could be improved, particularly through providing more emotional care. This
      coincided with an observed focus on physical care. The nurses reported a lack of
      support in caring for terminally ill patients and wanted more education on
      emotional issues and dealing with their own feelings. CONCLUSION: There is a need
      for an integrative approach in Spain that combines an educational programme with
      a supportive environment, focusing on developing nurses' competence to deliver
      emotional care and deal with their own feelings. Promoting a supportive
      environment might enable nurses to change their behaviour when caring for
      terminally ill patients and deal with patients' emotional as well as physical
      needs.

PMID- 23560318
TI  - Professional compassion fatigue: what is the true cost of nurses caring for the
      dying?
AB  - BACKGROUND: Emerging evidence describes some of the heavy tolls that health
      professionals experience as they deal with the continual loss of patients. Each
      patient and family has particular needs (physical, psychological, social, and
      spiritual) and is deserving of expert end-of-life care, and it is this intensity
      of need that places nurses at risk of professional compassion fatigue (PCF). AIM:
      This pilot study aimed at further exploration of the prevalence of PCF among
      hospice and palliative care nurses, as well as the nature of its effects and any
      coping strategies that nurses adopt. METHODOLOGY: A descriptive qualitative study
      was undertaken using semi-structured interviews with six highly experienced,
      purposively sampled nurses from a home health agency in northeast U.S.A. RESULTS:
      All six of the participants recognised the risks of developing PCF, and one was
      clearly experiencing PCF at the time of interview. Signs and symptoms were
      described and strategies for avoiding and alleviating PCF were discussed.
      CONCLUSION: There are clear physical and emotional health consequences for nurses
      who provide hospice and palliative care over extended periods of time. Further
      research is needed into the extent of the problem, specific causes, and coping
      strategies.

PMID- 23560319
TI  - Men's experiences delivering palliative home health care in rural South Africa:
      an exploratory study.
AB  - AIMS: The study reported here formed part of a larger study that explored the
      experiences of health-care workers providing palliative care in patients' homes
      in rural South Africa.This paper hones in on the experiences of male caregivers.
      Zulu culture has been strongly patriarchal and the gender of a caregiver may
      affect both patients' and caregivers' experiences. METHODS: The study was
      exploratory, qualitative, and combined a visual methodology with unstructured
      interviews. The setting was a hospice and three home-based care organisations in
      rural KwaZulu-Natal, South Africa. Participants were a male Zulu nurse and two
      male informal home-based caregivers who have been trained in components of
      palliative care. RESULTS: These male caregivers appeared to care deeply and
      altruistically for their patients and appeared to provide gender-appropriate care
      for male patients. Female patients were wary of being cared for by a man, for
      example having concerns that male caregivers may perpetrate physical abuse,
      including rape. Thus, challenges of being a male caregiver included the potential
      to not be appreciated by and/or to be subject to physical and verbal abuse from
      the community they serve. CONCLUSIONS: This study contests South African
      literature that presents male caregivers in a negative way. It emphasises a need
      to value and support male caregivers. The challenges faced by male caregivers are
      largely unexplored and further research is required as men could potentially play
      a valuable part in providing palliative care in rural homes.

PMID- 23560320
TI  - [Diagnostic value of contrast-enhanced ultrasonography in different pathological
      types and differentiated grades of primary liver carcinoma].

PMID- 23560321
TI  - In response.

PMID- 23560323
TI  - In response.

PMID- 23560324
TI  - Nine 'secret' keys to unlock breakthrough results.

PMID- 23560325
TI  - Model of the synthesis of trisporic acid in Mucorales showing bistability.
AB  - An important substance in the signalling between individuals of Mucor-like fungi
      is trisporic acid (TA). This compound, together with some of its precursors,
      serves as a pheromone in mating between (+)- and (-)-mating types. Moreover,
      intermediates of the TA pathway are exchanged between the two mating partners.
      Based on differential equations, mathematical models of the synthesis pathways of
      TA in the two mating types of an idealised Mucor-fungus are here presented. These
      models include the positive feedback of TA on its own synthesis. The authors
      compare three sub-models in view of bistability, robustness and the reversibility
      of transitions. The proposed modelling study showed that, in a system where
      intermediates are exchanged, a reversible transition between the two stable
      steady states occurs, whereas an exchange of the end product leads to an
      irreversible transition. The reversible transition is physiologically favoured,
      because the high-production state of TA must come to an end eventually. Moreover,
      the exchange of intermediates and TA is compared with the 3-way handshake widely
      used by computers linked in a network.

PMID- 23560326
TI  - Symbolic approach to verification and control of deterministic/probabilistic
      Boolean networks.
AB  - A Boolean network (BN) is well known as one of the models of biological networks
      such as gene regulatory networks, and has been extensively studied. In this
      study, for a BN, the verification/control problems are discussed. First, a
      probabilistic model including both synchronous and asynchronous Boolean dynamics
      is derived. This model can be generalised as a probabilistic BN. Next, a solution
      method of the verification/control problems is proposed, based on a probabilistic
      model checker PRISM. Finally, the PRISM-based method is applied to an apoptosis
      network and a WNT5A network. The proposed approach provides us an easy and
      convenient tool for analysis and control of biological networks.

PMID- 23560327
TI  - Design of biomolecular network modifications to achieve adaptation.
AB  - A biomolecular network is called adaptive if its output returns to the original
      value after a transient response even under a persisting stimulus. The conditions
      for adaptation have been investigated thoroughly with systems theory approaches
      in the literature and it is easy to check whether they are satisfied in the
      linear approximation. In contrast, it is in general not easy to modify a non
      adaptive network model such that it gains adaptive behaviour, especially for
      medium- and large-scale networks. The authors present a systematic approach based
      on the notion of kinetic perturbations to construct adaptive biomolecular network
      models from non-adaptive ones. An advantage of kinetic perturbations in this
      application is that neither the stoichiometry nor the steady state of the system
      is changed. Furthermore, the method covers both parameter and network structure
      modifications and can be applied to any reaction rate formalism and even to
      medium-scale or partially unknown models. The approach is exemplified at a small-
      and a medium-sized biomolecular network, illustrating its potential to
      systematically evaluate the different network modifications for adaptation. The
      proposed method will be useful either in iterative model building to construct
      mathematical models of adaptive biomolecular networks, or in synthetic biology
      where it can be applied to design or modify synthetic networks for adaptation.

PMID- 23560329
TI  - Paper withdrawn by the authors before the issue release.

PMID- 23560328
TI  - Computing enclosures for uncertain biochemical systems.
AB  - In this study, the authors present a novel method that provides enclosures for
      state trajectories of a non-linear dynamical system with uncertainties in initial
      conditions and parameter values. It is based on solving positivity conditions by
      means of semi-definite programmes and sum of squares decompositions. The method
      accounts for the indeterminacy of kinetic parameters, measurement uncertainties
      and fluctuations in the reaction rates because of extrinsic noise. This is
      particularly useful in the field of systems biology when one seeks to determine
      model behaviour quantitatively or, if this is not possible, semiquantitatively.
      The authors also demonstrate the significance of the proposed method to model
      selection in biology. The authors illustrate the applicability of their method on
      the mitogen-activated protein kinase signalling pathway, which is an important
      and reoccurring network motif that apparently also plays a crucial role in the
      development of cancer.

PMID- 23560330
TI  - Editor's introduction: intimate partner violence.

PMID- 23560331
TI  - [Update on microRNAs research in sarcoma: review the literature and proposal of
      the clinical application].

PMID- 23560332
TI  - [II. Research of signal transduction on sarcoma].

PMID- 23560333
TI  - [III. Development of molecular targeting therapy to musculoskeletal tumor].

PMID- 23560334
TI  - Sexual Assault Prevention and Response (SAPR) Program. Final rule.
AB  - This part implements Department of Defense (DoD) policy and assigns
      responsibilities for the SAPR Program on prevention, response, and oversight to
      sexual assault. It is DoD policy to establish a culture free of sexual assault by
      providing an environment of prevention, education and training, response
      capability, victim support, reporting procedures, and accountability that
      enhances the safety and wellbeing of all persons covered by this regulation.

PMID- 23560335
TI  - Putting revenge and forgiveness in an evolutionary context.
AB  - In this response, we address eight issues concerning our proposal that human
      minds contain adaptations for revenge and forgiveness. Specifically, we discuss
      (a) the inferences that are and are not licensed by patterns of contemporary
      behavioral data in the context of the adaptationist approach; (b) the theoretical
      pitfalls of conflating proximate and ultimate causation; (c) the role of
      development in the production of adaptations; (d) the implications of proposing
      that the brain's cognitive systems are fundamentally computational in nature; (e)
      our preferred method for considering the role of individual differences in
      computational systems; (f) applications of our proposal to understanding
      conflicts between groups; (g) the possible implications of our views for
      understanding the operation of contemporary criminal justice systems; and (h) the
      question of whether people ever "genuinely" forgive.

PMID- 23560336
TI  - Partner choice, fairness, and the extension of morality.
AB  - Our discussion of the commentaries begins, at the evolutionary level, with issues
      raised by our account of the evolution of morality in terms of partner-choice
      mutualism. We then turn to the cognitive level and the characterization and
      workings of fairness. In a final section, we discuss the degree to which our
      fairness-based approach to morality extends to norms that are commonly considered
      moral even though they are distinct from fairness.

PMID- 23560337
TI  - "SOS: hiding the truth is just hiding the harm".

PMID- 23560338
TI  - Nurse levels link with death rates.

PMID- 23560339
TI  - "The speak out safely campaign empowers those who whistleblow".

PMID- 23560340
TI  - "Most children with type 1 diabetes get inadequate care".

PMID- 23560341
TI  - Identifying patients for insulin pump therapy.
AB  - More people with type I diabetes are switching from multiple daily injections to
      a continuous subcutaneous insulin infusion (CSII), otherwise known as insulin
      pump therapy. This article provides an over view of the concept and general
      principals of CSII.

PMID- 23560342
TI  - Improving diabetes care for young people.

PMID- 23560343
TI  - Using social networks to help patients self-care.
AB  - Social networks are creating new ways for people with long-term conditions to
      seek support and offering new ways for health professionals to communicate with
      patients who have long-term conditions. There is evidence this may be helpful but
      nurses need to be skilled at operating in these new digital spaces to support
      patients effectively. This article discusses the growing use of social networks
      in long-term conditions, focusing on their use in diabetes care.

PMID- 23560344
TI  - Mandatory registration for healthcare assistants.

PMID- 23560345
TI  - Creating smoke-free homes for children.
AB  - This article describes a tool that was designed to help nurses deliver health
      education on the subject of passive smoking. The tool is based on a Scottish
      study, which encouraged mothers to identify their own strategies for reducing
      smoking in the home in order to protect their children from being exposed to
      second-hand smoke. It is designed to give nurses and other health professionals
      who work with families and children the knowledge, skills and confidence they
      need to raise the issue of second-hand smoke with parents and help them to find
      their own solutions to reducing smoking in the home. This article also takes into
      consideration the implications for nursing practice that relate to raising the
      issue of exposing children to second-hand smoke with parents and carers.

PMID- 23560346
TI  - Changes needed to cope with multimorbidity.

PMID- 23560347
TI  - The rewards of cancer care.

PMID- 23560348
TI  - Care for the parts, power the whole.

PMID- 23560350
TI  - The unmet medical needs of correctional populations in the United States.
AB  - The goal of this study was to document the health needs of members in the
      criminal justice system and the capacity of the system to meet those needs. Using
      data from the National Criminal Justice Treatment Practices survey, we estimated
      the number of adults under correctional control who need medical care and the
      capacity of the correctional system to provide needed care. A mailed survey of
      431 adult correctional agencies and administrators was used to define the
      capacity and techniques of the correctional system to meet the medical needs of
      the offender population. Most offenders in jail and prison received tuberculosis
      screening, physical health services, and mental health screening and treatment.
      Screening for sexually transmitted diseases (STDs) and provision of
      detoxification or methadone maintenance were universally absent, regardless of
      criminal justice setting. Community corrections settings were lacking in most
      health care areas. Prisons and jails are constitutionally mandated to provide
      health care; however, community corrections agencies are not federally required
      to provide health services. While community correction settings have the lowest
      provision of health care services, prisons and jails also demonstrate a
      deficiency in most services, but particularly for STD screening, substance abuse
      detoxification, and opioid maintenance therapies.

PMID- 23560349
TI  - HIV testing among Deep South residents with serious psychological distress.
AB  - OBJECTIVE: To describe the prevalence of serious psychological distress among
      Deep South residents and human immunodeficiency virus (HIV) testing among Deep
      South residents with serious psychological distress. METHODS: Data from the 2007
      Behavioral Risk Factor Surveillance System (BRFSS) survey from Georgia,
      Louisiana, Mississippi, and South Carolina were used for this study. Andersen's
      behavioral model of health care use provided the conceptual framework for the
      study. The Kessler 6 was used to dichotomize the sample as having or not having
      serious psychological distress. chi2 Test and multivariate logistic regression
      analyses were performed on the weighted data. RESULTS: Only 5.7% of our sample
      had experienced serious psychological distress in the past 30 days. A majority
      proportion of persons with serious psychological distress (54.9%) had been tested
      for HIV. HIV testing was slightly more prevalent among males with serious
      psychological distress (63%) than females with serious psychological distress
      (60%). Predisposing factors (age, race/ethnicity, and urbanization) were
      confounders of HIV testing among both males and females with serious
      psychological distress. Enabling factors (income, health care access) were only
      confounders of HIV testing among males with serious psychological distress.
      CONCLUSION: Future HIV prevention and management efforts should consider the
      potential role of concurrent serious psychological distress in impacting an
      individual's daily life and health activities such as self-care, caring for
      family, and maintaining employment.

PMID- 23560351
TI  - Psychosocial and sociocultural correlates of depressive symptoms among diverse
      African American women.
AB  - African American women are faced with many challenges regarding their historical,
      cultural, and social structural position in the United States that may heighten
      their vulnerability for depression, one of the most prevalent disorders that can
      engender poor functionality. The purpose of this cross-sectional pilot study was
      to foster greater understanding about the occurrence and correlates of depressive
      symptoms among a diverse convenience sample of 63 African American women
      recruited from a comprehensive primary health care clinic (n = 23), a small
      private academic institution (n = 25), and an urban community setting (n = 15).
      Self-report data concerning selected psychological, sociocultural, and biological
      factors were collected. Descriptive statistics, Pearson product moment
      correlation, and analysis of variance were used to analyze data. Results
      indicated several similarities and differences among the 3 groups of women
      concerning levels of depressive symptoms and their correlates. Among the total
      sample, symptoms of depression were mild among 65% of the women. Depressive
      symptoms were significant and positively associated with negative and ruminative
      thinking (r = 0.79, p < .01), low self-esteem (r = 0.58, p < .01), stressful life
      events (r = 0.43, p < .05), low social support (r = 0.46, p <.01), depression
      stigma (r = 0.36, p < 01), and indication of chronic diseases (r = 0.34, p <
      .01). Depressive symptoms were significant and negatively associated with
      resiliency (r = -0.48, p < .01) and spiritual well-being (r = -.47, p < .01).
      This research adds to the empirical data concerning contributors to depressive
      symptoms for African American women.

PMID- 23560352
TI  - Race and psychiatric diagnostic patterns: understanding the influence of hospital
      characteristics in the National Hospital Discharge Survey.
AB  - Historically, blacks have been more frequently diagnosed with schizophrenia and
      less frequently diagnosed with mood disorders than whites. Our understanding of
      why these disparities exist has primarily focused on patient and clinician
      characteristics and failed to examine the influence of social contextual factors
      such as hospital characteristics on diagnostic patterns. We analyzed data from
      the 2007 National Hospital Discharge Survey, a large national database of
      hospital inpatient stays. The paper examines whether race influences inpatient
      diagnoses before and after adjustment for select patient and hospital
      characteristics. Results indicate that blacks were 3-fold more likely to be
      diagnosed with schizophrenia (odds ratio [OR], 3.68; 95% confidence interval
      [CI], 2.96-4.57) or a psychotic disorder (OR, 3.39; 95% CI, 2.90-3.96) than
      whites. However, blacks were less likely than whites to be diagnosed with bipolar
      disorder (OR, 0.60; 95% CI, 0.50-0.72) or mood disorder (OR, 0.50; 95% CI, 0.43
      0.58). These same diagnostic patterns persisted after adjustment for selected
      patient and hospital characteristics. These results provide confirmation of
      trends observed in earlier studies of single hospitals with smaller sample sizes.
      Further research is necessary to determine whether the hospital characteristics
      selected for these analyses are appropriate proxy measures of factors that
      influence diagnostic judgment in inpatient settings.

PMID- 23560353
TI  - Beliefs and attitudes toward obstructive sleep apnea evaluation and treatment
      among blacks.
AB  - OBJECTIVE: Although blacks are at higher risk for obstructive sleep apnea (OSA),
      they are not as likely as their white counterparts to receive OSA evaluation and
      treatment. This study assessed knowledge, beliefs, and attitudes towards OSA
      evaluation and treatment among blacks residing in Brooklyn, New York. METHODS:
      Five focus groups involving 39 black men and women (aged > or =18 years) were
      conducted at State University of New York (SUNY) Downstate Medical Center in
      Brooklyn to ascertain barriers preventing or delaying OSA evaluation and
      treatment. RESULTS: Misconceptions about sleep apnea were a common theme that
      emerged from participants' responses. Obstructive sleep apnea was often viewed as
      a type of insomnia, an age-related phenomenon, and as being caused by certain
      bedtime activities. The major theme that emerged about barriers to OSA evaluation
      was unfamiliarity with the study environment. Barriers were categorized as:
      problems sleeping in a strange and unfamiliar environment, unfamiliarity with the
      study protocol, and fear of being watched while sleeping. Barriers to continuous
      positive airway pressure (CPAP) treatment adoption were related to the confining
      nature of the device, discomfort of wearing a mask while they slept, and concerns
      about their partner's perceptions of treatment. CONCLUSION: Results of this study
      suggest potential avenues for interventions to increase adherence to recommended
      evaluation and treatment of OSA. Potential strategies include reducing
      misconceptions about OSA, increasing awareness of OSA in vulnerable communities,
      familiarizing patients and their partners with laboratory procedures used to
      diagnose and treat OSA. We propose that these strategies should be used to inform
      the development of culturally and linguistically tailored sleep apnea
      interventions to increase awareness of OSA among blacks who are at risk for OSA
      and associated comorbidities.

PMID- 23560354
TI  - The relationship between functional health literacy and adherence to emergency
      department discharge instructions among Spanish-speaking patients.
AB  - INTRODUCTION: Adherence to emergency department (ED) discharge instructions among
      immigrant Spanish-speaking populations in the United States is suboptimal. Our
      objectives were to: (1) investigate associations between functional health
      literacy (FHL) and ED discharge instruction adherence in Spanish-speaking
      populations, and (2) compare the ED adherence rates of Spanish speakersto English
      speakers. METHODS: Using a matched cohort design, the FHL of adult native Spanish
      speakers in a tertiary care ED was assessed using the Test of Functional Health
      Literacy of Adults in Spanish (TOHFLA-S). Gender-matched and age-matched native
      English speakers were assessed using TOHFLA. TOFHLA scores range from 1 to 100
      with adequate FHL cutoff at 74. Excluded patients were those aged less than 19
      years, unwilling, prisoners, institutionalized, extremely ill, with a psychiatric
      complaint, in receipt of nonspecific instructions for follow-up, or with poor
      vision. A second interview assessed adherence with follow-up appointments and
      filling prescriptions. RESULTS: Fifty matched pairs were enrolled. Spanish
      speakers were less likely to understand discharge instructions (Spanish speakers,
      78%; English speakers, 94%; p < .0001) or to keep follow-up appointments (Spanish
      speakers, 46%; English speakers, 83%; p <.0001). TOFHLA for Spanish speakers
      averaged 62 vs 93 for English speakers (p < .0001). FHL was associated with
      understanding of and adherence to discharge instructions for Spanish speakers.
      Further, Spanish speakers reported lack of understanding as a primary reason for
      nonadherence. CONCLUSION: Spanish-speaking patients were less likely to comply
      with discharge instructions and scored lower on a test of FHL than English
      speaking patients. Poor adherence to ED discharge instructions was associated
      with lower FHL scores for our Spanish-speaking population. Alternative methods of
      providing discharge instructions to this population of patients should be
      explored.

PMID- 23560355
TI  - Effort required to contact primary care providers after newborn screening
      identifies sickle cell trait.
AB  - People with heterozygous status for sickle cell disease (also called sickle cell
      trait) are essentially healthy, but evidence of rare health problems has
      increased interest in screening adolescents and young adults prior to enlisting
      in athletics or military service. Ironically, almost everyone with sickle cell
      trait is already identified during routine newborn screening for sickle cell
      disease, but this identification may never reach the parents. As part of a larger
      statewide study of communication after newborn screening, we decided to document
      the amount of labor required to connect sickle cell trait screening results with
      primary care providers (PCPs). Case review methods examined records and call logs
      from the first 150 cases in a 42-month project. Our study procedures identified
      PCPs for 136 of 150 infants (90.6%); a total of 266 phone calls were needed. We
      identified 9 categories of experiences, ranging from incorrect baby names to
      restrictions on accepting Medicaid patients. Cases demonstrate that it is
      possible to connect with most PCPs after newborn screening despite warnings about
      difficulties with this population. Success was due to persistence, relationships
      with clinics and hospitals, and Internet search capabilities. If sickle cell
      trait identification is necessary to protect health, then only modest increases
      in effort will be needed to reduce disparities in service.

PMID- 23560356
TI  - A survey of ocular diseases in an isolated rural Haitian community: a
      retrospective evaluation.
AB  - PURPOSE: To report the prevalence and incidence of ophthalmic pathology from a
      small, rural town in Haiti and to determine the leading causes of blindness in
      this population. DESIGN: Retrospective study from 2002 to 2009. Data collected
      include visual acuity, intraocular pressure, and ocular and family history.
      METHOD: The study was conducted in a single center--Hospital de Lascahobas,
      Lascahobas, Haiti. Patients were natives of Lascahobas and the surrounding areas.
      Treatments were dispensed as indicated or warranted. RESULTS: A total of 3702
      patients were seen and examined: 51.52% were male and 49.48% were female. Ages
      ranged from 6 months to 92 years (mean, 48.69 SD +/- 49.94). Uncorrected
      refractive error was the most common diagnosis (53.27%), followed by presbyopia
      (43.76%), hyperopia (34.03%), and myopia (22.21%). A total 981 patients (26.50%)
      were diagnosed with cataract. Three hundred twenty-three (32.93%) cataract
      surgeries were performed. The overall postoperative complications rate was 9.29%.
      A total of 706 patients (19.07%) were diagnosed with glaucoma: 23.65% were
      glaucoma suspect and 76.35% were diagnosed with open-angle glaucoma (POAG). Of
      those diagnosed with POAG, 35.06% had end-stage (absolute) glaucoma. The mean age
      at diagnosis was 52.56 SD +/- 8.2 years. The mean intraocular pressure was 24.07
      and 25.60 mm Hg, and the mean cup to disc ratio of the right eye (OD) and the
      left eye (OS), respectively, was 0.67 and 0.72. CONCLUSIONS: Glaucoma was the
      most common cause for blindness. The most common cause of correctable vision loss
      was uncorrected refractive error followed by cataract. Providing constant eye
      care in this region will most likely decrease the incidence of correctable and
      permanent vision loss.

PMID- 23560357
TI  - Successful minority recruitment and adherence in physical activity Internet-based
      research: the WIN study.
AB  - BACKGROUND: Researchers studying physical activity often face challenges dealing
      with recruitment and resources, particularly when conducting longitudinal
      Internet-based research. Commonly raised methodological problems such as minority
      recruitment, participant commitment, and participant-staff involvement are
      addressed through a theoretically driven recruitment and adherence protocol in
      The Women's Exercise Injuries: Incidence and Risk Factors (WIN) Internet-based
      study. OBJECTIVES: The objectives of this paper were to review and suggest
      solutions to problems of: (1) low recruitment of diverse samples, (2) low
      adherence, and (3) staffing needs. METHODS: We recruited 1303 community-dwelling
      women and followed them through a multiple-phase, longitudinal, Internet-based
      study. Recruitment and adherence data were analyzed through descriptive methods
      and logistic regressions to examine participant adherence and sociodemographic
      factors and predictors of who entered the long-term phase of the study. RESULTS:
      We successfully retained 71.6% of the sample through 4 recruitment phases. Twenty
      seven percent of the initially recruited sample was racial/ethnically diverse,
      24% began the long-term phase, and 23% completed. Several strategies to enhance
      participant commitment were successfully used during the practice phase,
      providing a successful, low staff to participant ratio. Logistic regression
      indicated being married, being older, and having greater Internet skills were
      predictive of successfully entering the long-term phase of the study.
      CONCLUSIONS: Recruitment and compliance protocols were successful in meeting
      overall and racial/ethnic enrollment and recruitment goals. The theoretically
      based practice phase techniques were successful in re-engaging noncompliant
      participants. Strategies for minority enrollment and compliance are evaluated.

PMID- 23560358
TI  - When families talk: applying interpretative phenomenological analysis to African
      American families discussing their awareness, commitment, and knowledge of organ
      donation.
AB  - This paper applies interpretative phenomenological analysis as a tool to
      understand ways African American families discuss and make sense of their
      knowledge, awareness, and commitment of the organ donation process. African
      American families (n = 20) participated in self-directed conversations based on
      the organ donor model, which is grounded in the theory of reasoned action and the
      theory of motivated information management. Results indicate that the media
      strongly influences an individual's willingness to participate in the organ
      donation process and their commitment to further discuss their decisions with
      close family members. Greater attention should be given to cultural-specific
      campaigns to increase the number of African American donors.

PMID- 23560359
TI  - A rare case of acute renal failure due to tubulointerstitial nephritis and
      uveitis syndrome successfully treated with steroid.
AB  - We hereby describe a 49-year-old woman with acute renal failure due to
      tubulointerstitial nephritis and uveitis (TINU) syndrome. This patient presented
      with vomiting and nausea and was found to have chronic uveitis, elevated
      creatinine, and interstitial nephritis. The combination of tubulointerstitial
      nephritis and uveitis emerged the diagnosis of TINU syndrome after a stepwise
      examination for differential diagnosis. Clinical course and renal function
      improved quickly on oral steroids but not to normal range. TINU syndrome,
      although known to some ophthalmologists and nephrologists, is still rather
      obscure. TINU syndrome should be considered in patients with uveitis in
      combination with acute renal failure. The prognosis for the renal disorder is
      excellent, although the uveitis often recurs or remains chronic.

PMID- 23560360
TI  - Costoclavicular compression of the brachial plexus in a patient with a right
      aortic arch: MRI/MRA/MRV.

PMID- 23560361
TI  - We stand with you. What you need to know about HIV/AIDS.

PMID- 23560362
TI  - Transition from planar to nonplanar hydrogen bond networks in the solvation of
      aromatic dimers: propofol2-(H2O)(2-4).
AB  - Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous
      general anesthetic. In this work, the interaction of propofol dimer with 2-4
      water molecules was analyzed. The molecular aggregates were formed by using
      supersonic expansions, which maintain the molecules confined in a cold, collision
      free environment. The clusters were then examined by using a number of mass
      resolved laser-based spectroscopic techniques, including 2-color REMPI (resonance
      enhanced multiphoton ionization), UV/UV hole burning, and IR/UV double resonance.
      Two isomers were found for each stoichiometry, whose final structures were
      determined by comparison between the experimental data and those from density
      functional-theory calculations (M06-2X/6-31+G(d)). The analysis of the observed
      structures allows the conclusion that the water molecules always form hydrogen
      bond networks, whose contribution to the cluster's total binding energy increases
      with the number of water molecules. In the cluster with four water molecules, the
      two propofol molecules lose most of their contact points. In addition, the steric
      hindrance produces a change from cyclic to noncyclic hydrogen bond networks
      earlier than in similar systems.

PMID- 23560363
TI  - Retrospective follow-up assessment of prognostic variables associated with the
      outcome of periradicular surgery.
AB  - AIM: To investigate, retrospectively over a 1- to 16-year follow-up period, the
      strength and independence of the association of different patient-, tooth- and
      surgery-related prognostic variables with the outcome of periradicular surgery.
      METHODOLOGY: The study cohort included 171 teeth in 154 subjects. Clinical and
      radiographic measures along with the follow-up period were used to determine the
      healing outcome. For statistical analysis, results were dichotomized into
      healed/healing versus asymptomatic function/persistent disease cases. The
      association between candidate prognostic variables and asymptomatic
      function/persistent disease was analysed individually and adjusted for
      confounding using a multivariate binary logistic regression model. RESULTS: The
      percentage of success (healed/healing cases) was found to be 83.6%, whereas the
      percentage of failure (asymptomatic function/persistent disease cases) was found
      to be 16.4%. Whilst univariate analysis revealed a positive association of the
      presence of preoperative signs/symptoms, unsatisfactory quality of the coronal
      restoration, pronounced root-end resection bevel and inadequate quality of root
      end filling with asymptomatic function/persistent disease, after multivariate
      binary logistic regression analysis only the unsatisfactory quality of the
      coronal restoration and inadequate quality of root-end filling were strongly and
      independently associated with disease status. Confounding and interaction effects
      between candidate prognostic variables was noted. CONCLUSIONS: The findings of
      this study suggest that whilst the quality of both the coronal restoration and
      the root-end filling might be the foremost prognostic variables in periradicular
      surgery, there are synergistic biological interactive and mutually confounding
      effects with respect to root-end resection bevel and preoperative signs and/or
      symptoms that may be also associated with an increased proportion of failures
      after periradicular surgery.

PMID- 23560364
TI  - In vivo assessment of a carcinoid tumor using endocytoscopy.

PMID- 23560365
TI  - Encapsulating quantum dots into enveloped virus in living cells for tracking
      virus infection.
AB  - Utilization of quantum dots (QDs) for single virus tracking has attracted growing
      interest. Through modification of viral surface proteins, viruses can be labeled
      with various functionalized QDs and used for tracking the routes of viral
      infections. However, incorporation of QDs on the viral surface may affect the
      efficiency of viral entry and alter virus-cell interactions. Here, we describe
      that QDs can be encapsulated into the capsid of vesicular stomatitis virus
      glycoprotein (VSV-G) pseudotyped lentivirus (PTLV) in living cells without
      modification of the viral surface. QDs conjugated with modified genomic RNAs
      (gRNAs), which contain a packaging signal (Psi) sequence for viral genome
      encapsulation, can be packaged into virions together with the gRNAs. QD
      containing PTLV demonstrated similar entry efficiency as the wild-type PTLV.
      After infection, QD signals entered the Rab5+ endosome and then moved to the
      microtubule organizing center of the infected cells in a microtubule-dependent
      manner. Findings in this study are consistent with previously reported infection
      routes of VSV and VSV-G pseudotyped lentivirus, indicating that our established
      QD packaging approach can be used for enveloped virus labeling and tracking.

PMID- 23560366
TI  - Tacrolimus-induced severe cholestasis complicating renal transplantation.
AB  - Tacrolimus, a calcineurin inhibitor, is a potent immunosuppressive agent used by
      a majority of transplanters across the globe. Its adverse effects include
      nephrotoxicity, neurotoxicity, new onset diabetes after transplant, gastro
      intestinal toxicity, hepatotoxicity, and thrombotic microangiopathy. Tacrolimus
      induced hepatotoxicity is a very uncommon side effect. We report a case of
      tacrolimus-induced hepatotoxicity in the form of cholestatic hepatitis a renal
      transplant recipient. Hepatotoxicity did not decrease after dose reduction;
      however, normalization of liver enzymes occurred after discontinuing tacrolimus.

PMID- 23560367
TI  - Nonadherence to guidelines in the management of hepatocellular carcinoma: an
      Italian or universal phenomenon?

PMID- 23560368
TI  - Chemotherapy and immunomodulation: from immunogenic chemotherapies to novel
      therapeutic strategies.

PMID- 23560369
TI  - Functional genomics to identify unforeseen cancer drug targets.

PMID- 23560371
TI  - Future challenges for the treatment of liver tumors.
AB  - The annual World Congress of the International Association of Surgeons,
      Gastroenterologists and Oncologists (IASGO) was held in Bangkok, Thailand, from 5
      9 December 2012, hosted under the auspices of the President of the Association,
      Masatoshi Makuuchi and the General Secretary Nicolas Lygidakis. The President of
      the Congress and of the local committee was Nopadol Wora-Urai from Bangkok
      University (Bangkok, Thailand). The organization of the congress was excellent,
      and both the location and the kindness of the local people were marvellous. The
      congress was supported by 665 participants from 62 countries, including speakers
      from Europe, America, Africa, Asia and Australia. The program included symposia,
      videos, free papers and poster sessions. The scientific sessions also provided
      live surgery and lunch lectures. The congress offered the opportunity to exchange
      knowledge about the challenges and controversies involved in the management of
      abdominal diseases. This paper analyzes current possibilities and future
      expectations for the diagnosis and treatment of liver tumors, especially
      hepatocellular carcinomas and liver metastases from colorectal cancer.

PMID- 23560372
TI  - Selection and management of hepatocellular carcinoma patients with sorafenib:
      recommendations and opinions from an Italian liver unit.
AB  - Sorafenib (SO) was the first systemic agent to demonstrate a significant
      improvement in overall survival in patients with advanced hepatocellular
      carcinoma (HCC); international guidelines now recommend SO as a first-line
      treatment in patients with unresectable HCC who are not eligible for locoregional
      therapies and maintain preserved liver function. However, therapy with SO may
      require close management to further optimize the clinical outcomes and limit the
      onset of adverse events (AEs). SO has been in use at our Liver Unit (Avellino,
      Italy) for over 4 years, and in that time 85 patients with HCC have been treated
      with SO. Here we describe how patients with HCC are managed with SO in our unit
      where management is based on three pivotal strategies: targeted patient
      selection; use of dose escalation to increase compliance and reduce AEs; and
      adoption of measures to prevent and manage AEs and to provide open access for
      patients.

PMID- 23560373
TI  - Future radiation therapy: photons, protons and particles.
AB  - Radiation therapy plays a critical role in the current management of cancer
      patients. The most common linear accelerator-based treatment device delivers
      photons of radiation. In an ever more precise fashion, state-of-the-art
      technology has recently allowed for both modulation of the radiation beam and
      imaging for this treatment delivery. This has resulted in better patient outcome
      with far fewer side effects than were achieved even a decade ago. Recently, a
      push has begun for proton therapy, which may have clinical advantage in select
      indications, although significant limitations for these devices have become
      apparent. In addition, currently, heavy particle therapy has been touted as a
      potential means to improve cancer patient outcomes. This article will highlight
      current benefits and drawbacks to modern radiation therapy and speculate on
      future tools that will likely dramatically improve radiation oncology.

PMID- 23560374
TI  - Efficacy versus safety concerns for aerosol chemotherapy in non-small-cell lung
      cancer: a future dilemma for micro-oncology.
AB  - Inhaled chemotherapy was first used more than 30 years ago. Since then, numerous
      chemotherapeutic agents have been used in either in vitro or in vivo studies.
      Several aspects of the methodology of the drug administration have been
      thoroughly demonstrated and explained. However, the safety concerns of these
      studies were not thoroughly investigated and different results regarding the same
      drug formulations have been reported. There are cases where the studies failed to
      demonstrate the long-term effects of the chemotherapeutic drug formulations to
      the lung parenchyma. Acute and latent effects observed in a small number of human
      trial studies are still under investigation of inhaled chemotherapy
      administration. This review provides data regarding all up-to-date inhaled
      chemotherapy studies and presents the methodological parameters of the safety
      measures incorporated. In addition, a commentary regarding the safety concerns
      for the medical staff participating in these studies will be presented.

PMID- 23560375
TI  - Redirection of T-cell effector functions for cancer therapy: bispecific
      antibodies and chimeric antigen receptors.
AB  - T cells are the most potent cells of the immune system; however, they fail in the
      immunosurveillance of tumors. In previous decades, scientists began studying
      methods to take advantage of T-cell potency in cancer therapy by redirecting them
      against tumors independently from the T-cell receptor-defined specificity. Among
      different approaches, the most promising are the use of bispecific antibodies and
      T-cell engineering to create chimeric antigen receptors. Bispecific antibodies,
      by simultaneously recognizing target antigen and an activating receptor on the
      surface of an immune effector cell, offer an opportunity to redirect immune
      effector cells to kill cancer cells. The other approach is the generation of
      chimeric antigen receptors by fusing extracellular antibodies to intracellular
      signaling domains. Chimeric antigen receptor-engineered T cells are able to
      specifically kill tumor cells in a MHC-independent way. The efficacy of these
      reagents in different formats has been clinically validated and will be presented
      here.

PMID- 23560376
TI  - Incidence and prognosis of synchronous colorectal carcinomatosis.
AB  - The aim of this article was to review the literature on synchronous peritoneal
      carcinomatosis (PC) from colorectal cancer. Synchronous PC of colorectal cancer
      origin is a rare disease with an incidence ranging from 4 to 7% of colorectal
      cancer patients and is exclusively peritoneal in half of cases. Synchronous PC is
      more frequently associated with primary tumors that are at an advanced stage.
      After macroscopically complete resection (R0/R1) of synchronous PC, without
      associated intraperitoneal chemotherapy, the 5-year survival rates range from 24
      to 36%. Complete cytoreductive surgery plus intraperitoneal chemotherapy at the
      time of diagnosis is probably the best therapeutic option. If no intraperitoneal
      treatment can be given, no resection should be performed and an accurate
      description should be made. If a limited synchronous PC has been resected with
      the primary tumor without intraperitoneal treatment, the authors recommend a
      systematic second-look surgery in an experienced center.

PMID- 23560377
TI  - Targeting mechanisms of resistance to anti-EGF receptor therapy in KRAS wild-type
      colorectal cancer: the path to more personalized medicine.
AB  - The targeting of EGF receptors (EGFRs) in metastatic colorectal cancer has
      improved the outcome of patients with KRAS wild-type tumors. However, these
      improvements have been modest and do not translate across all patients with KRAS
      wild-type tumors. Better understanding of the EGFR pathway has led to the
      exploration of variable novel potential biomarkers of resistance and response to
      anti-EGFR therapy. This manuscript will focus on recently identified mechanisms
      of resistance to anti-EGFR therapy in KRAS wild-type colorectal cancer.
      Subsequently, an assessment will be presented on how the current understanding of
      some of these mechanisms of resistance has led, and will lead, to novel
      therapeutic opportunities in the management of colorectal cancer.

PMID- 23560378
TI  - Oncogene and non-oncogene addiction in inflammation-associated cancers.
AB  - Many cancers originate in tissues that are chronically inflamed, and the
      inflammatory microenvironment is considered to promote the progression of
      malignancy, including initiation, growth, angiogenesis, invasion and metastasis.
      The molecular mechanism of inflammation-induced progression of cancers has been
      widely discussed. Oncogene and non-oncogene addiction have been proposed as two
      distinct but complementary theories to explain the initiation and development of
      cancers. Furthermore, they also play a role in cancer-associated inflammation. A
      solid understanding of oncogene and non-oncogene addiction in cancer-associated
      inflammatory microenvironments will help to exploit cancer drug targets for
      cancer prevention and clinical treatment.

PMID- 23560379
TI  - Surgical quality of care in esophageal malignancies.
AB  - AIM: Esophagectomy is the primary surgical treatment for localized malignant
      neoplasms of the esophagus, and while outcomes have shown that substantial
      improvement has been made, the ceiling for improvement is still high. METHODS: A
      total of 2506 publications published from January 2002 to March 2012 were
      identified from PubMed, MEDLINE and the Cochrane Library using the keywords:
      'esophagectomy', 'esophagus', 'neoplasm' and 'cancer' to identify quality key
      surgical articles in esophagectomy that were broken down into three groups:
      preoperative, intraoperative and postoperative care. DISCUSSION: There have been
      limited preoperative surgical trials, mostly in preoperative antibiotic use,
      which have led to changes in surgical management. Key and substantial changes
      have occurred in the intraoperative management for esophageal malignancies around
      surgical anastomosis technique and anesthesia. Nutritional outcomes still remain
      a key challenge, and currently there is no established standard of care in the
      postoperative management of esophagectomy patients. CONCLUSION: We established
      quality parameters for leak rates, overall morbidity and mortality, and these
      form the foundation from which all esophageal surgeons should rank their results.
      We then utilized the techniques described above to maintain those rates or,
      better yet, to significantly improve those rates in each surgeons' practice.

PMID- 23560380
TI  - T(2)-weighted combined with diffusion-weighted images for evaluating prostatic
      transition zone tumors at 3 Tesla.
AB  - AIM: We hypothesize that the combination of T(2)-weighted (T(2)W) MRI with
      diffusion-weighted imaging (DWI) methods provides a powerful clinical application
      for the differential diagnosis of prostate cancer and benign lesion in the
      prostatic transition zone (TZ). METHODS: This retrospective study included 113
      patients who were diagnosed with TZ lesions by MRI. The apparent diffusion
      coefficient values were compared between biopsy-proven benign and malignant
      lesions. RESULTS: The apparent diffusion coefficient values for the malignant
      nodules were significantly lower than those of the benign nodules. The area under
      the curve values for T(2)W imaging combined with DWI and T(2)W imaging alone were
      0.991 and 0.884, respectively. CONCLUSION: T(2)W combined with DWI provides a
      powerful tool for noninvasive differentiation between malignant and benign
      prostatic hyperplasia nodules in the prostatic TZ.

PMID- 23560381
TI  - Reversing resistance of multidrug-resistant hepatic carcinoma cells with
      parthenolide.
AB  - AIM: To investigate the mechanism of reversing resistance of a hepatic carcinoma
      multidrug-resistant cell BEL-7402/5-FU with parthenolide (PTL). MATERIALS &
      METHODS: BEL-7402/5-FU cells were treated with different concentrations of PTL
      and/or 5-fluorouracil. The proliferation inhibition rates, NF-kappaB, P
      glycoprotein, MRP, Bcl-2, WNT1 and p53 levels were determined. RESULTS: The
      results showed that PTL did not only have proliferation inhibition influence on
      BEL-7402/5-FU in a concentration-dependent manner, but also significantly
      increased the proliferation inhibition role of 5-fluorouracil on BEL-7402/5-FU,
      to reverse the resistance of hepatic carcinoma-resistant cells. PTL could also
      inhibit the NF-kappaB activity and the expression of P-glycoprotein, MRP, Bcl-2
      and WNT1, and increase the expression of p53. CONCLUSION: Our research suggests
      that clinical administration of PTL may be useful for hepatic carcinoma patients.

PMID- 23560382
TI  - Diagnostic use of epitope detection in monocytes blood test for early detection
      of colon cancer metastasis.
AB  - A follow-up strategy in cancer aftercare can result in early detection of
      metastasis and/or recurrence. Therefore, sensitive and reliable diagnostic tests
      that are easy to perform are needed. Here, the authors present the combined use
      of the epitope detection in monocytes (EDIM)-TKTL1 and EDIM-Apo10 blood test in
      aftercare monitoring of a patient with colon carcinoma. Whereas the established
      tumor markers CEA and CA19-9 did not indicate metastasis even at a timepoint
      where clinical signs and imaging techniques already demonstrated metastasis, the
      combined application of the EDIM-TKTL1 and the EDIM-Apo10 blood tests was
      positive 9 months before detection of metastasis. These findings - taken together
      with recently published evaluation data of the EDIM-TKTL1 blood test - suggest
      that the combined application of the EDIM-TKTL1 and the EDIM-Apo10 blood tests
      might indicate metastasis earlier than established tumor markers and could serve
      as sensitive and noninvasive methods that might be used for early detection of
      colon cancer metastasis.

PMID- 23560384
TI  - A randomized trial of the Positive Thoughts and Action program for depression
      among early adolescents.
AB  - This study was conducted to compare the outcomes of a group-based cognitive
      behavioral preventive intervention (Positive Thoughts and Actions [PTA]) tailored
      to youth in middle school with a brief, individually administered supportive
      intervention (Individual Support Program [ISP]). A randomized, controlled trial
      was conducted with 120 early adolescents (72 girls, 48 boys; age = 11-15 years)
      who had elevated depressive symptoms and were selected from a school-based
      population. Measures of internalizing problems, externalizing problems, personal
      adjustment, school problems, and interpersonal relations were obtained from
      parents, youth, and/or teachers at preintervention (Time 1) and postintervention
      (Time 2, 5-7 months after preintervention). General linear model repeated
      measures analyses yielded a significant Group * Time interaction on youth
      reported, but not parent-reported, depressive symptoms and internalizing
      symptoms. Youth in the PTA group showed greater decreases following intervention
      compared to youth who received ISP, yielding effect sizes (Cohen's d) of 0.36 for
      depressive symptoms, 95% CI [-.02, .73], and 0.44, 95% CI [.05, .82], for
      internalizing symptoms. PTA youth also showed improvements in their personal
      adjustment (sense of inadequacy, self-esteem), and parent-reported social skills,
      but no differences emerged between groups for externalizing symptoms, school
      problems, or interpersonal relationships. Cognitive-behavioral preventive
      interventions in which youth engage in personal goal-setting and practice social
      emotional skills, such as PTA, may be beneficial for the reduction of depressive
      symptoms over and above general support and empathy. 

PMID- 23560385
TI  - Successful novel treatment of recalcitrant transient acantholytic dermatosis
      (Grover disease) using red light 5-aminolevulinic acid photodynamic therapy.

PMID- 23560387
TI  - Hormonal and surgical treatments for endometriosis and risk of epithelial ovarian
      cancer.
AB  - OBJECTIVE: Whether hormonal or surgical treatment of endometriosis is associated
      with risk of epithelial ovarian cancer. DESIGN: Nested case-control study.
      SETTING: Sweden. POPULATION: All women with a first-time discharge diagnosis of
      endometriosis in 1969-2007 were identified using the National Swedish Patient
      Register and constituted our study base. METHODS: By linkage to the National
      Swedish Cancer Register we identified all women diagnosed with epithelial ovarian
      cancer at least one year after the endometriosis diagnosis (cases). Two controls
      per case with no ovarian cancer before the date of cancer diagnosis of the case
      were randomly selected from the study base and matched for year of birth. Two
      hundred-and-twenty cases and 416 controls entered the study. Information on
      hormonal and surgical treatments and other reproductive factors was extracted
      from medical records according to pre-specified protocols. Conditional logistic
      regression was used for all calculations. MAIN OUTCOME MEASURES: Crude and
      adjusted odds ratios (OR) with 95% confidence intervals (CI) for all hormonal as
      well as surgical treatments. RESULTS: There was a significant association between
      one-sided oophorectomy, as well as for radical extirpation of all visible
      endometriosis, and ovarian cancer risk in both univariate analyses (crude OR
      0.42, 95% CI 0.28-0.62 and OR 0.37, 95% CI 0.25-0.55, respectively) and
      multivariate analyses (adjusted OR 0.19, 95% CI 0.08-0.46 and OR 0.30, 95% CI
      0.12-0.74, respectively). CONCLUSIONS: One-sided oophorectomy as well as radical
      extirpation of all visible endometriosis is protective against later development
      of ovarian cancer.

PMID- 23560388
TI  - Diagnosis by real-time polymerase chain reaction of pathogens and antimicrobial
      resistance genes in bone marrow transplant patients with bloodstream infections.
AB  - BACKGROUND: Early identification of pathogens and antimicrobial resistance in
      bloodstream infections (BSIs) decreases morbidity and mortality, particularly in
      immunocompromised patients. The aim of the present study was to compare real-time
      polymerase chain reaction (PCR) with commercial kits for detection of 17
      pathogens from blood culture (BC) and 10 antimicrobial resistance genes. METHODS:
      A total of 160 BCs were taken from bone marrow transplant patients and screened
      with Gram-specific probes by multiplex real-time PCR and 17 genus-specific
      sequences using TaqMan probes and blaSHV, blaTEM, blaCTX, blaKPC, blaIMP, blaSPM,
      blaVIM, vanA, vanB, and mecA genes by SYBR Green. RESULTS: Twenty-three of 33
      samples identified by phenotypic testing were concordantly positive by BC and
      real-time PCR. Pathogen identification was discordant in 13 cases. In 12 of 15
      coagulase-negative staphylococci, the mecA gene was detected and four
      Enterococcus spp. were positive for vanA. Two blaCTX and three blaSHV genes were
      found by quantitative PCR. The blaKPC and metallo-beta-lactamase genes were not
      detected. Five fungal species were identified only by real-time PCR. CONCLUSIONS:
      Real-time PCR could be a valuable complementary tool in the management of BSI in
      bone marrow transplants patients, allowing identification of pathogens and
      antimicrobial resistance genes.

PMID- 23560389
TI  - Apoplastic mesophyll signals induce rapid stomatal responses to CO2 in Commelina
      communis.
AB  - Previous studies have suggested that the mesophyll contributes to stomatal CO(2)
      responses. The effects of changes in CO(2) concentration (100 or 700 ppm) on
      stomatal responses in red or white light were examined microscopically in a leaf
      segment, an epidermal strip and an epidermal strip placed on a mesophyll segment
      of Commelina communis, all mounted on a buffer-containing gel. In both red and
      white light, stomata of the leaf segment opened/closed rapidly at low/high CO(2).
      In red light, epidermal strip stomata barely responded to CO(2). In white light,
      they opened at low CO(2), but hardly closed at high CO(2). Stomata of the
      epidermal strip placed on the mesophyll responded in the same manner as those on
      the leaf segment. Insertion of a doughnut-shaped cellophane spacer (but not
      polyethylene spacer) between the epidermal strip and the mesophyll hardly altered
      these responses. Stomata in leaf segments treated with 3-(3,4-dichlorophenyl)-1,1
      dimethylurea (DCMU), a photosynthesis inhibitor, did not open in red light, but
      opened/closed at low/high CO(2) in white light. These results indicate that the
      apoplast transfer of 'mesophyll signals' and the stomatal opening at low CO(2)
      are dependent on photosynthesis, whereas the stomatal closure at high CO(2) is
      independent of photosynthesis.

PMID- 23560391
TI  - Temperature-induced emission enhancement of star conjugated copolymers with
      poly(2-(dimethylamino)ethyl methacrylate) coronas for detection of bacteria.
AB  - A facile strategy for temperature-induced emission enhancement of star conjugated
      copolymers has been developed for biodetection. The star copolymers (HCP-star
      PDMAEMAs) with different poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)
      chain lengths were synthesized from the hyperbranched conjugated polymer (HCP)
      macroinitiator by atom transfer radical polymerization (ATRP). The star
      conjugated copolymers exhibited interesting thermoresponsive phase transitions
      with adjustable lower critical solution temperature (LCST) depending on the pH of
      copolymer solution. Above the LCST, the emission of HCP-star-PDMAEMAs was
      enhanced greatly through restriction of intermolecular aggregation of conjugated
      polymer cores by the collapse of PDMAEMA arms. By changing the PDMAEMA length,
      the emission performance of HCP-star-PDMAEMAs could be readily adjusted.
      Correspondingly, this temperature-dependent emission enhancement of HCP-star
      PDMAEMAs was successfully applied in the highly sensitive detection of bacteria.
      Due to the existence of a hyperbranched conjugated core and many thermo
      responsive PDMAEMA arms, the detection limit of E. coli could reach 10(2) cfu mL(
      1).

PMID- 23560390
TI  - Enhancing osteoconductivity of fibrin gels with apatite-coated polymer
      microspheres.
AB  - Fibrin gels are a promising material for use in promoting bone repair and
      regeneration due to their ease of implant formation, tailorability,
      biocompatibility, and degradation by natural processes. However, these materials
      lack necessary osteoconductivity to nucleate calcium, integrate with surrounding
      bone, and promote bone formation. Polymeric substrata formed from poly(lactide-co
      glycolide) (PLG) are widely used in bone tissue engineering. A carbonated apatite
      layer of bone-like mineral can be successfully grown on the surface of PLG
      microspheres after a multiday incubation process in modified simulated body
      fluid. Such coatings improve the osteoconductivity of the polymer, provide
      nucleation sites for cell-secreted calcium, and enhance the potential
      osseointegration with host tissue. We examined the capacity of mineralized
      polymeric microspheres suspended within fibrin hydrogels to enhance the
      osteoconductivity of fibrin gels and increase the osteogenic potential of these
      materials. The inclusion of microparticles, both nonmineralized and mineralized,
      reduced the capacity of mesenchymal stem cells (MSCs) to contract the gel. When
      cultured in osteogenic media, we detected a near linear increase in both calcium
      and phosphate incorporation in gels containing mineralized microspheres and
      entrapped MSCs. The osteoconductivity of acellular fibrin gels with mineralized
      and nonmineralized microspheres was assessed in a rodent calvarial bone defect
      over 12 weeks. Compared to untreated rodent calvarial bone defects, we detected
      significant increases in early vascularization when treated with fibrin gels,
      with greater vascularization, on average, occurring with gels containing
      microspheres. We detected a trend for increased bone mineral density in gels
      containing mineralized microspheres after 12 weeks. These findings demonstrate
      that the osteoconductivity of fibrin gels can be increased by inclusion of
      mineralized microspheres, but additional signals may be required to rapidly
      accelerate bone repair. 

PMID- 23560392
TI  - UV-induced transformation of four halobenzoquinones in drinking water.
AB  - Halobenzoquinones (HBQs) are a group of emerging disinfection byproducts (DBPs)
      found in treated drinking water. Because the use of UV treatment for disinfection
      is becoming more widespread, it is important to understand how the HBQs may be
      removed or changed due to UV irradiation. Water samples containing four HBQs, 2,6
      dichloro-1,4-benzoquinone (DCBQ), 2,3,6-trichloro-1,4-benzoquinone (TCBQ), 2,6
      dichloro-3-methyl-1,4-benzoquinone (DCMBQ), and 2,6-dichloro-1,4-benzoquinone
      (DBBQ), were treated using a modified bench scale collimated beam device,
      mimicking UV treatment. Water samples before and after UV irradiation were
      analyzed for the parent compounds and products using a high performance liquid
      chromatography tandem mass spectrometry (HPLC-MS/MS) method. As much as 90% of
      HBQs (0.25 nmol L(-1)) in both pure water and tap water were transformed to other
      products after UV254 irradiation at 1000 mJ cm(-2). The major products of the
      four HBQs were identified as 3-hydroxyl-2,6-dichloro-1,4-benzoquinone (OH-DCBQ)
      from DCBQ, 5-hydroxyl-2,6-dichloro-3-methyl-1,4-benzoquinone (OH-DCMBQ) from
      DCMBQ, 5-hydroxyl-2,3,6-trichloro-1,4-benzoquinone (OH-TCBQ) from TCBQ, and 3
      hydroxyl-2,6-dibromo-1,4-benzoquinone (OH-DBBQ) from DBBQ. These four OH-HBQs
      were further modified to monohalogenated benzoquinones when the UV dose was
      higher than 200 mJ cm(-2). These results suggested possible pathways of UV
      induced transformation of HBQs to other compounds. Under the UV dose commonly
      used in water treatment plants, it is likely that HBQs are partially converted to
      other halo-DBPs. The occurrence and toxicity of these mixed DBPs warrant further
      investigation to understand whether they pose a health risk.

PMID- 23560393
TI  - Intestinal absorption mechanism of mirabegron, a potent and selective beta3
      adrenoceptor agonist: involvement of human efflux and/or influx transport
      systems.
AB  - Mirabegron, a weak-basic compound, is a potent and selective beta3-adrenoceptor
      agonist for the treatment of overactive bladder. Mirabegron extended release
      formulation shows dose-dependent oral bioavailability in humans, which is likely
      attributable to saturation of intestinal efflux abilities leading to higher
      absorption with higher doses. This study evaluated the membrane permeability of
      mirabegron and investigated the involvement of human intestinal transport
      proteins in the membrane permeation of mirabegron. Transcellular transport and
      cellular/vesicular uptake assays were performed using Caco-2 cells and/or human
      intestinal efflux (P-glycoprotein [P-gp], breast cancer resistance protein
      [BCRP], and multidrug resistance associated protein 2 [MRP2]) and influx (peptide
      transporter 1 [PEPT1], OATP1A2, and OATP2B1) transporter-expressing cells,
      vesicles, or Xenopus laevis oocytes. The absorptive permeability coefficients of
      mirabegron in Caco-2 cells (1.68-1.83 * 10(-6) cm/s) at the apical and basal pH
      of 6.5 and 7.4, respectively, were slightly higher than those of nadolol (0.97
      1.41 * 10(-6) cm/s), a low permeability reference standard, but lower than those
      of metoprolol and propranolol (both ranged from 8.49 to 11.6 * 10(-6) cm/s),
      low/high permeability boundary reference standards. Increasing buffer pH at the
      apical side from 5.5 to 8.0 gradually increased the absorptive permeation of
      mirabegron from 0.226 to 1.66 * 10(-6) cm/s, but was still less than the value in
      the opposite direction (11.0-14.2 * 10(-6) cm/s). The time- and concentration
      dependent transport of mirabegron was observed in P-gp-expressing cells and
      OATP1A2-expressing oocytes with apparent Km values of 294 and 8.59 MUM,
      respectively. In contrast, no clear BCRP-, MRP2-, PEPT1-, or OATP2B1-mediated
      uptake of mirabegron was observed in their expressing vesicles or cells. These
      findings suggest that mirabegron has low-to-moderate membrane permeability and P
      gp is likely to be involved in its efflux into the lumen in the intestinal
      absorption process. The results also suggest that mirabegron could possibly be
      transported by intestinal influx transporters as well as simple diffusion.

PMID- 23560394
TI  - Accumulation of anthocyanin and associated gene expression in radish sprouts
      exposed to light and methyl jasmonate.
AB  - Radish (Raphanus sativus) sprouts have received attention as an important dietary
      vegetable in Asian countries. The flavonoid pathway leading to anthocyanin
      biosynthesis in radishes is induced by multiple regulatory genes as well as
      various developmental and environmental factors. This study investigated
      anthocyanin accumulation and the transcript level of associated genes in radish
      sprouts exposed to light and methyl jasmonate (MeJA). The anthocyanin content of
      sprouts exposed to light and treated with MeJA was higher than that of sprouts
      grown under dark conditions without MeJA, and the highest anthocyanin content was
      observed within 6-9 days after sowing (DAS). Transcript levels of almost all
      genes were increased in radish sprouts grown in light conditions with 100 MUM
      MeJA relative to sprouts grown under dark conditions with or without MeJA
      treatment, especially at 3 DAS. The results suggest that light and MeJA treatment
      applied together during radish seedling development enhance anthocyanin
      accumulation.

PMID- 23560395
TI  - Iododerma following topical povidone-iodine application.
AB  - A 43-year-old male patient presented with two well-demarcated, elevated plaques,
      measuring 4 cm in diameter, with yellow-black crusts over it that appeared 3 d
      earlier. With the help of history, physical examination and histopathological
      features, the patient was diagnosed with iododerma secondary to topical povidone
      iodine use. Iododerma develops frequently after oral or intravenous but rarely
      after topical use of iodine. Its pathogenesis is not well-known though it is
      widely believed that it is a delayed hypersensitivity reaction.

PMID- 23560396
TI  - Cognitive impairment and depression in the early 60s: which is more problematic
      in terms of instrumental activities of daily living?
AB  - AIM: We evaluated the impact of cognitive impairment and depression on functional
      impairment in people aged in their early 60s. METHODS: This cross-sectional study
      included 3034 inhabitants of a rural area of Korea aged 60-64 years. The Korean
      version of the Mini-Mental State Examination (MMSE-K), the Geriatric Depression
      Scale (GDS-15), and Lawton's Instrumental Activities of Daily Living (IADL) Scale
      were used to assess cognitive impairment, depression and functional impairment.
      RESULTS: A total of 30.8% of participants reported that they were dependent for
      at least one of the items on the IADL scale, and the overall prevalence of
      cognitive impairment and depression was 17.3% and 25.9%, respectively. The
      results showed that cognitive impairment had a stronger relationship with IADL
      impairment than did depression (odds ratio [OR] = 4.91, 95% confidence interval
      [CI] 3.91-6.17; c-statistics = 0.647 and OR = 2.05, 95% CI 1.67-2.50; c
      statistics = 0.622, respectively). In particular, subclinical levels of the MMSE
      K and GDS-15 score were associated with IADL impairment in participants without
      cognitive impairment or depression (OR = 0.73, 95% CI 0.67-0.80, OR = 1.09, 95%
      CI 1.03-1.16, per 1 point score increase, respectively). Only the MMSE-K score
      showed a significant association in participants with either cognitive impairment
      or depression, or both. Our findings also showed the independent association of
      IADL impairment with age, employment status, education and type of insurance.
      CONCLUSIONS: Compared with depression, cognitive impairment was more strongly
      associated with IADL impairment. Subclinical level of cognitive impairment and
      depression were also associated with IADL impairment in mentally healthy
      participants. Therefore, early intervention is required to prevent further
      decline.

PMID- 23560397
TI  - Bicyclic peptide ligands pulled out of cysteine-rich peptide libraries.
AB  - Bicyclic peptide ligands were found to have good binding affinity and target
      specificity. However, the method applied to generate bicyclic ligands based on
      phage-peptide alkylation is technically complex and limits its application to
      specialized laboratories. Herein, we report a method that involves a simpler and
      more robust procedure that additionally allows screening of structurally more
      diverse bicyclic peptide libraries. In brief, phage-encoded combinatorial peptide
      libraries of the format X(m)CX(n)CX(o)CX(p) are oxidized to connect two pairs of
      cysteines (C). This allows the generation of 3 * (m + n + o + p) different
      peptide topologies because the fourth cysteine can appear in any of the (m + n +
      o + p) randomized amino acid positions (X). Panning of such libraries enriched
      strongly peptides with four cysteines and yielded tight binders to protein
      targets. X-ray structure analysis revealed an important structural role of the
      disulfide bridges. In summary, the presented approach offers facile access to
      bicyclic peptide ligands with good binding affinities.

PMID- 23560398
TI  - Foreword. Advanced nanobiomaterials for tissue engineering and regenerative
      medicine.

PMID- 23560399
TI  - Starting with form, emerging with function: nanofibrous scaffolds for tissue
      engineering of orthopedic tissues.

PMID- 23560400
TI  - Electrospun core/shell nanofibers: a promising system for cartilage and tissue
      engineering?

PMID- 23560401
TI  - Combining photobiology and nanobiotechnology: a step towards improving medical
      protocols based on advanced biological models.

PMID- 23560402
TI  - Nanoparticle-based paste could have promise in bone defect repair.

PMID- 23560403
TI  - IKVAV-functionalized self-assembling peptide hydrogel for improved neural stem
      cell transplantation.

PMID- 23560404
TI  - Interview: Nanomedicine: past, present and future.
AB  - Professor Thomas Webster received his Bachelor of Science degree in chemical
      engineering from the University of Pittsburgh (PA, USA) in 1995. He subsequently
      received his Masters degree in biomedical engineering in 1997 from Rensselaer
      Polytechnic Institute (NY, USA). He completed his PhD at the same institution in
      2000. Currently, Professor Webster is the Department Chair and Professor of
      Chemical Engineering at Northeastern University (MA, USA). He previously held the
      position of Associate Professor for the Division of Engineering at Brown
      University (RI, USA) and the Division of Orthopedic Surgery at Brown University
      Medical School. He is an elected Fellow of the American Institute for Medical and
      Biological Engineering, which represents the top 2% of all medical and biological
      engineers. Professor Webster's research has led to the formation of nine start-up
      companies. He has authored over 400 peer-reviewed publications and issued more
      than 30 patents.

PMID- 23560405
TI  - Electrospun human keratin matrices as templates for tissue regeneration.
AB  - AIM: The aim of this work was to study the feasibility of fabricating human hair
      keratin matrices through electrospinning and to evaluate the potential of these
      matrices for tissue regeneration. MATERIALS & METHODS: Keratin was extracted from
      human hair using Na2S and blended with poly(ethylene oxide) in the weight ratio
      of 60:1 for electrospinning. Physical morphology and chemical properties of the
      matrices were characterized using scanning electron microscopy and Fourier
      transform infrared spectroscopy, respectively. Cell viability and morphology of
      murine and human fibroblasts cultured on the matrices were evaluated through the
      Live/Dead((r)) assay and scanning electron microscopy. RESULTS: Electrospun
      keratin matrices were successfully produced without affecting the chemical
      conformation of keratin. Fibroblasts cultured on keratin matrices showed healthy
      morphology and penetration into matrices at day 7. CONCLUSION: Electrospun human
      hair keratin matrices provide a bioinductive and structural environment for cell
      growth and are thus attractive as alternative templates for tissue regeneration.

PMID- 23560406
TI  - Multiarray cell stretching platform for high-magnification real-time imaging.
AB  - AIM: This article reports the development of a multiarray microchip with real
      time imaging capability to apply mechanical strains onto monolayered cell
      cultures. MATERIALS & METHODS: Cells were cultured on an 8-um thick membrane that
      was positioned in the microscope focal plane throughout the stretching process.
      Each stretching unit was assembled from three elastomeric layers and a glass
      coverslip. A programmable pneumatic control system was developed to actuate this
      platform. Multiple stretching experiments were conducted with various cell lines.
      RESULTS: The platform provides a maximum uniform strain of 69%. Acute and long
      term cell morphological changes were observed. The supreme imaging capability was
      verified by real-time imaging of transfected COS-7 stretching and poststretching
      imaging of immunofluorescence-stained PTK2. CONCLUSION: The platform reported
      here is a powerful tool for studying mechanically induced physiological changes
      in cells. Such a device could be used in tissue regeneration for maintaining
      essential cell growth conditions.

PMID- 23560407
TI  - Cryogenic electrospinning: proposed mechanism, process parameters and its use in
      engineering of bilayered tissue structures.
AB  - BACKGROUND: Conventional electrospun scaffolds have very small pores, thus
      limiting cellular infiltration, tissue ingrowth and vascularization in tissue
      engineering applications. The cryogenic electrospinning process overcame the
      small pore size constraints found in conventional electrospun scaffolds. AIM: The
      aim of this paper is to propose a mechanism for cryogenic electrospinning and how
      scaffold pore size can be controlled. MATERIALS & METHODS: We studied the roles
      of ice crystals in controlling the pore size of cryogenic electrospun scaffolds
      (CES). Based on this understanding, we have successfully fabricated a bilayered
      scaffold with distinctly different pore sizes. RESULTS: Our study showed that CES
      pore size was dependent on the structure of the frost layer formed and hence the
      factors affecting ice deposition. The bilayered scaffold was able to support the
      coculture of human dermal fibroblasts and keratinocytes. CONCLUSION: The larger
      pores of CES add versatility to the use of electrospun scaffolds in tissue
      engineering applications.

PMID- 23560408
TI  - Elastin-based silver-binding proteins with antibacterial capabilities.
AB  - AIM: To develop novel elastin-like materials with antibacterial capabilities.
      MATERIALS & METHODS: Artificial proteins bearing AG3 silver-binding motifs (GPG
      AG3) were constructed using genetic engineering. GPG-AG3 materials were prepared
      as GPG-AG3 protein aggregates as well as chemically crosslinked spin-coated thin
      films. Both GPG-AG3 protein aggregates and thin films were incubated in silver
      nitrate solution and characterized using electron microscopy. RESULTS &
      DISCUSSION: The GPG-AG3 substrates prepared in this work have the ability to
      nucleate silver under physiological conditions. When tested against gram-negative
      Escherichia coli bacterial culture, silver-coated GPG-AG3 materials were able to
      inhibit bacterial growth, confirming their antibacterial properties. CONCLUSION:
      Antibacterial artificial protein materials were successfully developed,
      demonstrating promise for use as wound dressings and biomedical implant coatings.

PMID- 23560409
TI  - Enhancing the biological performance of osteoconductive nanocomposite scaffolds
      through negative voltage electrospinning.
AB  - AIM: To investigate negative voltage electrospinning of fibrous nanocomposite
      scaffolds bearing negative electric charges (N-poled), and determine whether and
      how retained negative charges could influence the biological performance of
      scaffolds for bone tissue engineering. MATERIALS & METHODS: Poly(D,L-lactic acid)
      was used as the polymer matrix and carbonated hydroxyapatite nanospheres were the
      osteoconductive phase in the electrospun nanocomposite scaffolds. N-poled
      nanocomposite scaffolds were formed using negative voltage electrospinning, while
      conventional positive voltage electrospinning produced fibrous nanocomposite
      scaffolds bearing positive electric charges (P-poled). N-poled and P-poled
      scaffolds were systematically characterized and their biological performance was
      investigated through in vitro cell culture experiments. RESULTS & CONCLUSION: N
      poled and P-poled scaffolds retained charges for different periods of time after
      electrospinning. Both types of scaffolds supported cell spreading and promoted
      filopodia formation. Compared with P-poled scaffolds, N-poled scaffolds enhanced
      cell proliferation, alkaline phosphatase activity and mineralization. N-poled
      scaffolds offer distinct advantages for bone tissue engineering.

PMID- 23560410
TI  - Advanced nanobiomaterial strategies for the development of organized tissue
      engineering constructs.
AB  - Nanobiomaterials, a field at the interface of biomaterials and nanotechnologies,
      when applied to tissue engineering applications, are usually perceived to
      resemble the cell microenvironment components or as a material strategy to
      instruct cells and alter cell behaviors. Therefore, they provide a clear
      understanding of the relationship between nanotechnologies and resulting cellular
      responses. This review will cover recent advances in nanobiomaterial research for
      applications in tissue engineering. In particular, recent developments in
      nanofibrous scaffolds, nanobiomaterial composites, hydrogel systems, laser
      fabricated nanostructures and cell-based bioprinting methods to produce scaffolds
      with nanofeatures for tissue engineering are discussed. As in native niches of
      cells, where nanofeatures are constantly interacting and influencing cellular
      behavior, new generations of scaffolds will need to have these features to enable
      more desirable engineered tissues. Moving forward, tissue engineering will also
      have to address the issues of complexity and organization in tissues and organs.

PMID- 23560411
TI  - Advanced biofabrication strategies for skin regeneration and repair.
AB  - Skin is the largest organ of human body, acting as a barrier with protective,
      immunologic and sensorial functions. Its permanent exposure to the external
      environment can result in different kinds of damage with loss of variable volumes
      of extracellular matrix. For the treatment of skin lesions, several strategies
      are currently available, such as the application of autografts, allografts, wound
      dressings and tissue-engineered substitutes. Although proven clinically
      effective, these strategies are still characterized by key limitations such as
      patient morbidity, inadequate vascularization, low adherence to the wound bed,
      the inability to reproduce skin appendages and high manufacturing costs. Advanced
      strategies based on both bottom-up and top-down approaches offer an effective,
      permanent and viable alternative to solve the abovementioned drawbacks by
      combining biomaterials, cells, growth factors and advanced biomanufacturing
      techniques. This review details recent advances in skin regeneration and repair
      strategies, and describes their major advantages and limitations. Future
      prospects for skin regeneration are also outlined.

PMID- 23560412
TI  - Mechanoregulation of stem cell fate via micro-/nano-scale manipulation for
      regenerative medicine.
AB  - Recent developments in the field of mechanobiology have renewed the call for a
      better understanding of the role of mechanical forces as potent regulators and
      indicators of stem cell fate. Although it is well established that mechanical
      forces play a crucial role in guiding tissue development, little is known about
      how submicroscopic biomechanical forces can influence key stem cell behaviors.
      This review will detail the use of micro-/nano-technologies that are advancing
      our current understanding of stem cell mechanobiology, and mechanoregulation of
      stem cell fate using engineered surface topographies and small-scale patterning
      techniques. The involvement of focal adhesions and the cytoskeleton systems as a
      common biophysical impetus through which these mechanical signals are transduced
      via distinct signaling pathways will also be discussed. These insights are
      envisioned to provide the basis for the rational design of future biocompatible
      materials and may inspire alternative drug-free therapeutic strategies to manage
      diseased sites via biomechanical management.

PMID- 23560413
TI  - Nanocomposites for bone tissue regeneration.
AB  - Natural bone tissue possesses a nanocomposite structure that provides appropriate
      physical and biological properties. For bone tissue regeneration, it is crucial
      for the biomaterial to mimic living bone tissue. Since no single type of material
      is able to mimic the composition, structure and properties of native bone,
      nanocomposites are the best choice for bone tissue regeneration as they can
      provide the appropriate matrix environment, integrate desirable biological
      properties, and provide controlled, sequential delivery of multiple growth
      factors for the different stages of bone tissue regeneration. This article
      reviews the composition, structure and properties of advanced nanocomposites for
      bone tissue regeneration. It covers aspects of interest such as the biomimetic
      synthesis of bone-like nanocomposites, guided bone regeneration from inert
      biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone
      tissue regeneration. The design, fabrication, and in vitro and in vivo
      characterization of such nanocomposites are reviewed.

PMID- 23560414
TI  - Bioresponsive hydrogel scaffolding systems for 3D constructions in tissue
      engineering and regenerative medicine.
AB  - Among the diversity of scaffolding systems available, hydrogel remains a popular
      choice for tissue engineering applications. The current state-of-the-art
      bioresponsive hydrogels demand intricate designs in pursuit of acquiring desired
      timely responses, such as controlled release of biological factors, changes in
      mechanical properties and scaffold degradation, at the same rate as the natural
      extracellular matrix. In this review, a variety of bioresponsive hydrogels are
      discussed; in particular, bioactive and biodegradable hydrogels that facilitate
      cellular development and tissue morphogenesis are highlighted. Bioactive
      hydrogels are designed to deliver biomolecules such as cell-adhesive moieties and
      instructive ligands at close proximity to the cell for better uptake or exposure.
      Biodegradable hydrogels provide transient scaffolding support for therapeutic
      cell settlement while gradually degrading in response to physical or enzymatic
      stimuli. In addition, biomechanical stimuli from hydrogels can induce mutual
      constructive responses on cells and, hence, will also be covered in this review.

PMID- 23560415
TI  - The potential of multiblock polymer nanoparticles to attack tumors.

PMID- 23560416
TI  - Histologic and histomorphometric behavior of microgrooved zirconia dental
      implants with immediate loading.
AB  - PURPOSE: The study aims to assess the total soft tissue (ST) width, crestal bone
      level (CBL), bone-to-implant contact (BIC), and bone density (BD) for zirconia
      implants textured with microgrooved surfaces and immediately loaded. MATERIALS
      AND METHODS: This study included 51 implants; one implant from each study group
      was retained for surface characterization. The 48 remaining implants were
      inserted randomly in premolar areas of both sides of the healed edentulous lower
      jaws of foxhound dogs. They were divided into three groups of 16: control
      (titanium); test A (zirconia), and test B (microgrooved zirconia). The implants
      were splinted and covered with an acrylic bridge. A split-mouth design was used
      and immediate occlusal loading was applied on one side, while the other side did
      not have occlusal contact. ST, CBL, BIC, and BD were evaluated after 3 months.
      The effects of immediate loading on these parameters were analyzed. RESULTS: All
      the implants were osseointegrated. ST was established at 3 months with mean
      values of 2.9 +/- 0.4 mm for all groups. No differences were appreciated between
      loaded and unloaded sides regarding ST (p > .05). CBL showed a mean of 1.2 +/-
      0.3 mm for all groups without differences between loaded and unloaded sides (p >
      .05). BIC percentages were significantly higher for loaded all-microgrooved
      implants (p < .05). BD percentages were higher in areas close to all-microgrooved
      implants (p < .05) and significantly higher for loaded implants than unloaded.
      CONCLUSIONS: Within the limitations of the present study, it may be concluded
      that for zirconia dental implants with microgrooved surfaces and immediate
      loading, the thickness of STs remains stable resulting in 3 mm mean biologic
      width, that crestal bone preservation is related to insertion depth, and that
      higher BIC percentages and increased BD around implants microgrooved over the
      entire intraosseous area may be expected at 3 months following implant insertion
      and immediate loading.

PMID- 23560417
TI  - The Icebreaker Life Mission to Mars: a search for biomolecular evidence for life.
AB  - The search for evidence of life on Mars is the primary motivation for the
      exploration of that planet. The results from previous missions, and the Phoenix
      mission in particular, indicate that the ice-cemented ground in the north polar
      plains is likely to be the most recently habitable place that is currently known
      on Mars. The near-surface ice likely provided adequate water activity during
      periods of high obliquity, ~ 5 Myr ago. Carbon dioxide and nitrogen are present
      in the atmosphere, and nitrates may be present in the soil. Perchlorate in the
      soil together with iron in basaltic rock provides a possible energy source for
      life. Furthermore, the presence of organics must once again be considered, as the
      results of the Viking GCMS are now suspect given the discovery of the thermally
      reactive perchlorate. Ground ice may provide a way to preserve organic molecules
      for extended periods of time, especially organic biomarkers. The Mars Icebreaker
      Life mission focuses on the following science goals: (1) Search for specific
      biomolecules that would be conclusive evidence of life. (2) Perform a general
      search for organic molecules in the ground ice. (3) Determine the processes of
      ground ice formation and the role of liquid water. (4) Understand the mechanical
      properties of the martian polar ice-cemented soil. (5) Assess the recent
      habitability of the environment with respect to required elements to support
      life, energy sources, and possible toxic elements. (6) Compare the elemental
      composition of the northern plains with midlatitude sites. The Icebreaker Life
      payload has been designed around the Phoenix spacecraft and is targeted to a site
      near the Phoenix landing site. However, the Icebreaker payload could be supported
      on other Mars landing systems. Preliminary studies of the SpaceX Dragon lander
      show that it could support the Icebreaker payload for a landing either at the
      Phoenix site or at midlatitudes. Duplicate samples could be cached as a target
      for possible return by a Mars Sample Return mission. If the samples were shown to
      contain organic biomarkers, interest in returning them to Earth would be high.

PMID- 23560419
TI  - Multifactorial aetiology for bone disease in patients with haemophilia.

PMID- 23560418
TI  - The effect of bone marrow- and adipose tissue-derived mesenchymal stem cell
      transplantation on myocardial remodelling in the rat model of ischaemic heart
      failure.
AB  - This study aimed to investigate the effect of bone marrow- and adipose tissue
      derived mesenchymal stem cell (BM-MSC and AD-MSC respectively) transplantation on
      left ventricular function and infarct area (IA) in the rat model of ischaemic
      heart failure. In anaesthetized Wistar rats, the left coronary artery (LCA) was
      occluded for 40 min with subsequent reperfusion for 7 days. Seven days following
      surgery, the animals with LCA occlusion/reperfusion were randomized into three
      groups: (i) Controls received intramyocardial injection of vehicle at three
      different locations within the peri-infarct zone, (ii) BM-MSC: cells were
      injected in the same way as in previous group (10(6) ), (iii) AD-MSC: using the
      same protocol as used in the BM-MSC group. In addition there was also a sham
      treated group that had no injection. Two weeks following MSC transplantation, the
      hearts were isolated and perfused according to the Langendorff method followed by
      30-min global ischaemia and 90-min reperfusion. After this IA was determined
      histologically. During Langendorff perfusion initial and postischaemic LV
      functions were the same in all groups although LV pressure at the 10th minute of
      reperfusion was higher in the AD-MSC group compared to controls. However, LV
      pressure during 30-min global ischaemia was significantly higher in BM-MSC as
      compared to controls and AD-MSC. The sham treated animals showed the same results
      as those seen with BM-MSC. Thus, BM-MSC transplantation, in contrast to
      transplantation of AD-MSC, resulted in better preservation of the LV ability to
      contract during ischaemia. Furthermore, IA was significantly smaller in BM-MSC
      group as compared to the controls and the AD-MSC groups. Thus this study has
      demonstrated that treatment with BM-MSC both ameliorates LV function and reduces
      histological scar size.

PMID- 23560421
TI  - Self-absorption paradox is not a paradox: illuminating the dark side of self
      reflection.
AB  - Although considered an important component of a healthy personality, self
      reflection has not so far been shown to have any specific benefits for mental
      health. This research addresses this issue by taking into consideration two
      important suppressor variables, self-rumination and the need for absolute truth.
      The latter is an innovative variable, defined and presented in this research. The
      first two studies aimed to validate a new measure that acts as an operational
      definition of the need for absolute truth. The first study was conducted with two
      group of participants; the first group consisted of 129 females and 67 males,
      mean age = 20 years, and the second 182 females and 104 males, mean age = 27. In
      the second study, participants were 22 females and 18 males, mean age = 20.5. In
      the final study, conducted with 296 female, 163 male participants (mean age =
      37), suppressor effects were tested using structural equation modeling. The
      results showed that by taking account of these two suppressor variables,
      particularly the need for absolute truth, the expected relationship between self
      reflection and mental health was revealed. The need for absolute truth was shown
      to be crucial for understanding the effects of self-reflection on mental health,
      therefore it should be considered in all processes of psychotherapy.

PMID- 23560422
TI  - Prevalence and characterization of multidrug-resistant zoonotic Enterobacter spp.
      in poultry of Bangladesh.
AB  - Poultry and poultry products are major contributors of zoonotic pathogens.
      Limited data are available on Enterobacter spp. as a potent zoonotic pathogen in
      poultry. The present study is a first endeavor on the emergence of multidrug
      resistant zoonotic Enterobacter spp. and its prevalence arising from poultry in
      Bangladesh. Cloacal swabs from poultry samples of five different farms at Savar,
      Dhaka, Bangladesh were collected and from 106 isolates, 18 presumptive
      Enterobacter spp. were obtained. Antibiogram using 19 used antibiotics belonging
      to 15 major groups revealed that all of the 18 isolates were completely resistant
      to penicillin and rifampicin, but differed in their drug resistance pattern
      against ampicillin (94.4%), clindamycin (94.4%), erythromycin (94.4%), vancomycin
      (88.9%), sulfonamides (72.2%), imipenem (66.6%), streptomycin (55.6%),
      nitrofurantoin (33.3%), doxycycline (33.3%), tetracyclines (33.3%), cefepime
      (11.1%), and gentamicin (5.6%). All Enterobacter spp. were found to be plasmid
      free, implying that multidrug-resistant properties are chromosomal borne. The
      vanA and sulI were detected by polymerase chain reaction assay in 17 and 13
      isolates, respectively. Amplified ribosomal DNA restriction analysis and randomly
      amplified polymorphic DNA distributed the 18 multidrug-resistant Enterobacter
      spp. into three genotypes. Phylogenetic analysis of the representatives of the
      three genotypes using partial 16S rRNA gene sequence (approximately 900 bp)
      showed that the genotypically diverse groups belonged to Enterobacter hormaechei,
      E. cloacae, and E. cancerogenus, respectively. The clinical significance of the
      close relative Enterobacter spp. is indicative of their zoonotic potential.
      Therefore, urgent intervention is required to limit the emergence and spread of
      these bacteria in poultry feed as well as prudent use of antibiotics among
      poultry farmers in Bangladesh.

PMID- 23560423
TI  - Improving the utilization of research knowledge in agri-food public health: a
      mixed-method review of knowledge translation and transfer.
AB  - Knowledge translation and transfer (KTT) aims to increase research utilization
      and ensure that the best available knowledge is used to inform policy and
      practice. Many frameworks, methods, and terms are used to describe KTT, and the
      field has largely developed in the health sector over the past decade. There is a
      need to review key KTT principles and methods in different sectors and evaluate
      their potential application in agri-food public health. We conducted a structured
      mixed-method review of the KTT literature. From 827 citations identified in a
      comprehensive search, we characterized 160 relevant review articles, case
      studies, and reports. A thematic analysis was conducted on a prioritized and
      representative subset of 33 articles to identify key principles and
      characteristics for ensuring effective KTT. The review steps were conducted by
      two or more independent reviewers using structured and pretested forms. We
      identified five key principles for effective KTT that were described within two
      contexts: to improve research utilization in general and to inform policy-making.
      To ensure general research uptake, there is a need for the following: (1)
      relevant and credible research; (2) ongoing interactions between researchers and
      end-users; (3) organizational support and culture; and (4) monitoring and
      evaluation. To inform policy-making, (5) researchers must also address the
      multiple and competing contextual factors of the policy-making process. We also
      describe 23 recommended and promising KTT methods, including six synthesis (e.g.,
      systematic reviews, mixed-method reviews, and rapid reviews); nine dissemination
      (e.g., evidence summaries, social media, and policy briefs); and eight exchange
      methods (e.g., communities of practice, knowledge brokering, and policy
      dialogues). A brief description, contextual example, and key references are
      provided for each method. We recommend a wider endorsement of KTT principles and
      methods in agri-food public health, but there are also important gaps and
      challenges that should be addressed in the future.

PMID- 23560424
TI  - Seroprevalence and risk factors associated with brucellosis as a professional
      hazard in Pakistan.
AB  - The present study was conducted to determine the seroprevalence and identify risk
      factors associated with brucellosis in humans at high risk in the Potohar plateau
      of northeastern Pakistan. A total of 262 serum samples were collected from
      persons of different occupational groups: veterinary personnel, milkers, abattoir
      workers, livestock farmers, and others (drivers, security guards, housewives).
      Data related to gender, age, occupation, contact with animals, brucellosis
      related symptoms, consumption of raw milk, and geographical region were
      collected. The Rose Bengal plate test and the serum agglutination test were
      performed to determine the seroprevalence of brucellosis. The overall
      seroprevalence was found to be 6.9% (95% confidence interval [CI]: 4.1, 10.6).
      Real-time polymerase chain reaction assay showed that all cases were affected by
      Brucella abortus. Individuals who consumed raw milk had higher odds of
      brucellosis seropositivity. This is the first report of human brucellosis related
      to B. abortus in high-risk professionals from Pakistan by the combined use of
      serological and molecular methods.

PMID- 23560425
TI  - Increased recognition of non-O157 Shiga toxin-producing Escherichia coli
      infections in the United States during 2000-2010: epidemiologic features and
      comparison with E. coli O157 infections.
AB  - BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) are an important cause
      of diarrhea and the major cause of postdiarrheal hemolytic uremic syndrome. Non
      O157 STEC infections are being recognized with greater frequency because of
      changing laboratory practices. METHODS: Foodborne Diseases Active Surveillance
      Network (FoodNet) site staff conducted active, population-based surveillance for
      laboratory-confirmed STEC infections. We assessed frequency and incidence of STEC
      infections by serogroup and examined and compared demographic factors, clinical
      characteristics, and frequency of international travel among patients. RESULTS:
      During 2000-2010, FoodNet sites reported 2006 cases of non-O157 STEC infection
      and 5688 cases of O157 STEC infections. The number of reported non-O157 STEC
      infections increased from an incidence of 0.12 per 100,000 population in 2000 to
      0.95 per 100,000 in 2010; while the rate of O157 STEC infections decreased from
      2.17 to 0.95 per 100,000. Among non-O157 STEC, six serogroups were most commonly
      reported: O26 (26%), O103 (22%), O111 (19%), O121 (6%), O45 (5%), and O145 (4%).
      Non-O157 STEC infections were more common among Hispanics, and infections were
      less severe than those caused by O157 STEC, but this varied by serogroup. Fewer
      non-O157 STEC infections were associated with outbreaks (7% versus 20% for O157),
      while more were associated with international travel (14% versus 3% for O157).
      CONCLUSIONS: Improved understanding of the epidemiologic features of non-O157
      STEC infections can inform food safety and other prevention efforts. To detect
      both O157 and non-O157 STEC infections, clinical laboratories should routinely
      and simultaneously test all stool specimens submitted for diagnosis of acute
      community-acquired diarrhea for O157 STEC and for Shiga toxin and ensure that
      isolates are sent to a public health laboratory for serotyping and subtyping.

PMID- 23560426
TI  - Focus on medication management.

PMID- 23560430
TI  - Postoperative hemolytic uremic syndrome with renal cortical necrosis following
      laparoscopic hemicolectomy.
AB  - Non-Shiga-like toxin-producing Escherichia coli (STEC) or atypical hemolytic
      uremic syndrome (aHUS) is observed in 5-10% of all hemolytic uremic syndrome
      (HUS) cases, and usually develops secondary to infections, malignancies, drugs,
      transplantation, pregnancy, and autoimmune disease. However, there has been no
      report on adult onset HUS initiated by surgical procedures except
      transplantation. We report a 66-year-old woman who incurred renal impairment on
      the first day after laparoscopic hemicolectomy. Hemolytic anemia,
      thrombocytopenia, absence of Shiga toxin associated disease, normal ADAMTS13
      activity, and low serum C3 (not C4) were consistent with a diagnosis of aHUS. We
      performed plasma exchange with fresh frozen plasma. Nevertheless, deteriorated
      renal function was not recovered after the treatment. Although it is an uncommon
      postoperative complication, aHUS needs to be considered as a possible cause of
      acute kidney injury combined with thrombocytopenia and anemia after surgical
      procedures, considering its different treatment modality and poor outcomes.

PMID- 23560431
TI  - Assessment and functional impact of allocentric neglect: a reminder from a case
      study.
AB  - SR suffered a right hemispheric stroke more than 3 years ago, and now lives with
      left-sided hemiparesis and chronic spatial neglect due to damaged white matter
      pathways connecting the frontal, temporal and parietal regions. We report here
      that SR suffers from both viewer-centered (i.e., egocentric) and object-centered
      (i.e., allocentric) spatial neglect. Notably, unlike most neuropsychological and
      functional assessments that focus on egocentric deficits, a specialized
      neuropsychological figurative discrimination test (the Apples test) revealed SR's
      allocentric neglect. Further, using assessments sensitive to detect functional
      deficits related to allocentric neglect, we observed SR's difficulty in reading
      and using clocks, reflecting his object-centered errors in these everyday
      activities. SR's case suggests that allocentric-specific assessments, both
      neuropsychological and functional, are valuable in standard neglect examinations,
      particularly to predict daily function after stroke. We recommend that neglect
      related functional disability be distinguished further with respect to
      allocentric spatial deficits, and functional assessments for allocentric neglect
      should be validated in future large sample studies. Identifying allocentric
      neglect early, and learning about its influence on daily function, may enhance
      care quality and facilitate effective rehabilitation planning for stroke
      recovery. 

PMID- 23560432
TI  - Novel ferrocenyl-containing N-acetyl-2-pyrazolines inhibit in vitro angiogenesis
      and human lung cancer growth by interfering with F-actin stress fiber
      polimeryzation.
AB  - Cancer is a significant worldwide health problem generally because of lack of
      widespread and comprehensive early detection methods. Lung cancer is the leading
      cause of cancer deaths in men worldwide and the second leading cause of cancer
      deaths in women. To date, the available treatment regimens are not successful.
      For this reason, new targets for prevention and new agents for therapy need to be
      identified. The biological activities of some synthesized ferrocene-containing N
      acetylated-2-pyrazoline compounds were studied for this article. Their
      cytotoxicity (by methyl thiazol tetrazolium assay), as well as apoptotic (by 4'6
      diamidino-phenylindole and F-actin staining), antitumoral (colony-forming ability
      assay) and antiangiogenic activities (by tube formation), were evaluated for the
      first time on a human non-small-cell lung cancer (A549) cell line and a human
      umbilicial vein endothelial cell line. All compounds were cytotoxic, antitumoral
      and apoptotic against tumor cells in a dose-dependent manner. Compounds 2 and 3,
      which were noncytotoxic, could inhibit capillary vessel formation. Especially, N
      acetyl-5-ferrocenyl-3-(2-thienyl)-2-pyrazoline (2) may be used in the development
      of therapeutic agents for angiogenic diseases and cancer.

PMID- 23560433
TI  - Heterogeneity of interpersonal problems among depressed young adults:
      associations with substance abuse and pathological personality traits.
AB  - This study extended previous theory and research on interpersonal heterogeneity
      in depression by identifying groups of depressed young adults who differ in their
      type and degree of interpersonal problems, and by examining patterns of
      pathological personality traits and alcohol abuse among these groups. We examined
      the interpersonal problems, personality traits, and alcohol-related problems of
      172 college students with at least moderate levels of self-reported depression on
      the Patient Health Questionnaire (Spitzer, Kroenke, & Williams, 1999). Scores
      from the Inventory of Interpersonal Problems-Short Circumplex (Soldz, Budman,
      Demby, & Merry, 1995) were subjected to latent profile analysis, which classified
      individuals into 5 distinct groups defined by the types of interpersonal problems
      they experience (dominant, warm, submissive, cold, and undifferentiated). As
      hypothesized, groups did not differ in depression severity, but did show
      predicted patterns of differences on normative and maladaptive personality
      traits, as well as alcohol-related problems. The presence of clinically
      meaningful interpersonal heterogeneity in depression could have important
      implications for designing more individualized treatments and prevention efforts
      for depression that target diverse associated interpersonal problems. 

PMID- 23560434
TI  - Protective action of proanthocyanidin fraction from Medemia argun nuts against
      oxidative/nitrative damages of blood platelet and plasma components.
AB  - The oxidative/nitrative stress induced by different factors plays an important
      role in the pathogenesis of various disorders, including cardiovascular diseases
      and cancer. Proanthocyanidins have antioxidative properties and may protect
      biomolecules (lipids, DNA, and proteins) exposed to reactive oxygen and nitrogen
      species, including peroxynitrite (ONOO(-)). The effects of proanthocyanidin
      fraction from Medemia argun nuts on oxidative/nitrative protein damages
      (determined by such parameters as level of thiol groups, carbonyl groups, and
      nitrotyrosine residues) and on the amount of glutathione (as an important
      component of redox status; using HPLC) in human blood platelets and plasma after
      treatment with peroxynitrite were studied in vitro. The preincubation of blood
      platelets and plasma with proanthocyanidin fraction from M. argun nuts (0.5-50
      ug/ml) reduced the formation of 3-nitrotyrosine, diminished oxidation of thiol
      groups, and decreased the level of carbonyl groups in proteins caused by 100 uM
      peroxynitrite. An action of tested plant fraction and ONOO(-) evoked a
      significant increase of GSH in platelets and plasma in comparison with platelets
      and plasma treated with ONOO(-) only. The proanthocyanidin fraction from M. argun
      nuts can be useful as a protecting factor against oxidative/nitrative stress
      associated with different diseases (cancer, cardiovascular, and neurodegenerative
      diseases) and proanthocyanidins of M. argun nuts may be promising antioxidants.

PMID- 23560435
TI  - Endoscopic ultrasound-guided rendezvous procedure for unidentifiable papilla and
      non-dilated pancreatic duct (with video).

PMID- 23560436
TI  - Quality of life and satisfaction of patients after nonsurgical primary root canal
      treatment provided by undergraduate students, graduate students and endodontic
      specialists.
AB  - AIM: (i) To assess the impact of primary root canal treatment on the perceived
      quality of life amongst a cohort of Jordanian patients, (ii) to assess this
      cohort's satisfaction of their primary root canal treatment, and (iii) to
      evaluate the association of the level of training and experience of clinicians
      with these two parameters. METHODOLOGY: A systematic random sample of 302
      subjects was selected from patients who attended undergraduate, graduate and
      specialty clinics of Jordan University of Science and Technology. Participants
      were interviewed before and two weeks after completion of root canal treatment.
      The study instrument included the Oral Health Impact Profile questionnaire (Dugas
      et al. 2002) and seven semantic differential scales. Data analyses included
      descriptive statistics and nonparametric analyses. RESULTS: More than 90% of
      subjects reported improvements in the sense of taste, pain, eating, altering food
      temperature, self-consciousness, waking up during sleep, interruption of meals,
      difficulty to relax and difficulty to sleep after root canal treatment. There was
      no significant difference in terms of improvement amongst patients treated by
      specialists, graduate students or undergraduate students. The overall semantic
      differential score of intraoperative pain, pleasantness, chewing ability and
      general satisfaction was about 8. Satisfaction of root canal treatment by
      specialists was higher in terms of time involved, intraoperative pain,
      pleasantness and general satisfaction than those treatments by undergraduate
      students. Patients treated by specialist were least satisfied with the treatment
      cost compared to those patients treated by graduate or undergraduate students.
      CONCLUSIONS: The impact of root canal treatment on the quality of life was
      apparent. Satisfaction with root canal treatment approximates 8 on the semantic
      differential scale with preference for specialists over dental students.

PMID- 23560437
TI  - Natural organic matter concentration and hydrochemistry influence aggregation
      kinetics of functionalized engineered nanoparticles.
AB  - Understanding the colloidal stability of functionalized engineered nanoparticles
      (FENPs) in aquatic environments is of paramount importance in order to assess the
      risk related to FENPs. In this study, gold nanoparticles (GNPs) of 68 and 43 nm
      diameter, coated with citrate and 11-mercaptoundecanoic acid (MUA) respectively,
      were used as models of FENPs. Time-resolved dynamic light scattering was employed
      to investigate the aggregation kinetics of two types of GNPs. The results show
      that without Suwannee river natural organic matter (SRNOM), MUA coating resulted
      in greater stability than citrate coating for GNPs. Cations have a destabilizing
      effect on both GNPs following the order Ca(2+) ~ Mg(2+) >> Na(+); different
      anions (Cl(-) and SO4(2-)) showed no difference in effects. In the fast
      aggregation regime, adding SRNOM enhanced the stability of MUA-coated GNPs in
      both Ca(2+) and Mg(2+) solutions. However citrate-coated GNPs were only
      stabilized in Mg(2+) solution but enhanced aggregation occurred in high Ca(2+)
      concentration due to interparticle bridging. For the investigated GNPs and in the
      presence of SRNOM, Ca(2+) does not always act as a strong coagulant. This
      indicates that for the new materials emerging from the application of
      nanotechnology the well-described aggregation mechanisms of colloids in the
      environment require a detailed re-examination.

PMID- 23560438
TI  - Poly(vinyl alcohol) physical hydrogel nanoparticles, not polymer solutions, exert
      inhibition of nitric oxide synthesis in cultured macrophages.
AB  - Hydrogel nanoparticles (HNP) are an emerging tool of biomedicine with unique
      materials characteristics, scope, and utility. These hydrated, soft colloidal
      carriers can penetrate through voids with dimensions narrower than the size of
      the particle, provide stabilization for fragile biological cargo and allow
      diffusion and exchange of solutes with external phase. However, techniques to
      assemble HNP are few; solitary examples exist of biocompatible polymers being
      formulated into HNP; and knowledge on the biomedical properties of HNP remains
      rather cursory. In this work, we investigate assembly of HNP based on a polymer
      with decades of prominence in the biomedical field, poly(vinyl alcohol), PVA. We
      develop a novel method for production of PVA HNP through nanoprecipitation-based
      assembly of polymer nanoparticles and subsequent physical hydrogelation of the
      polymer. Polymer nanoparticles and HNP were visualized using scanning electron
      microscopy and fluorescence imaging, and characterized using dynamic light
      scattering and zeta potential measurements. Interaction of PVA HNP with mammalian
      cells was investigated using flow cytometry, viability screening, and
      measurements of nitric oxide production by cultured macrophages. The latter
      analyses revealed that PVA administered as a polymer solution or in the form of
      HNP resulted in no measurable increase in production of the inflammation marker.
      Unexpectedly, PVA HNP exerted a pronounced inhibition of NO synthesis by
      stimulated macrophages, that is, had an anti-inflammatory activity. This effect
      was accomplished with a negligible change in the cell viability and was not
      observed when PVA was administered as a polymer solution. To the best of our
      knowledge, this is the first observation of inhibition of NO synthesis in
      macrophages by administered nanoparticles and specifically hydrogel
      nanoparticles. Taken together, our results present PVA HNP as promising colloidal
      hydrogel nanocarriers for biomedical applications, specifically drug delivery and
      assembly of intracellular biosensors.

PMID- 23560439
TI  - Assessment of the anti-invasion potential and mechanism of select cinnamic acid
      derivatives on human lung adenocarcinoma cells.
AB  - Patients with lung adenocarcinoma are often diagnosed with metastasizing symptoms
      and die of early and distal metastasis. Metastasis is made up of a cascade of
      interrelated and sequential steps, including cell adhesion, extracellular matrix
      degradation, cell movement, and invasion. Hence, substances carrying the ability
      to stop one of the metastasis-associated steps could be a potential candidate for
      preventing tumor cells from metastasizing and prolonging the life of cancer
      patients. Cinnamic acid (CA) was demonstrated to be such a candidate for human
      lung adenocarcinoma cells. Nevertheless, the effectiveness of CA derivatives on
      invasion of lung cancer cells is still unclear. The aims of this study were to
      explore the mechanisms underlying several select CA derivatives against invasion
      of human lung adenocarcinoma A549 cells. The results revealed that caffeic acid
      (CAA), chlorogenic acid (CHA), and ferulic acid (FA) can inhibit phorbol-12
      myristate-13-acetate (PMA)-stimulated invasion of A549 cells at a concentration
      of >=100 MUM. The MMP-9 activity was suppressed by these compounds through
      regulating urokinase-type plasminogen activator (uPA), tissue inhibitor of
      metalloproteinase (TIMP)-1, plasminogen activator inhibitor (PAI)-1, and PAI-2;
      the cell-matrix adhesion was decreased by CAA only. The proposed molecular
      mechanism involved not only decreasing the signaling of MAPK and PI3K/Akt but
      also inactivating NF-kappaB, AP-1, and STAT3. In the present study, we selected
      CAA, CHA, and FA as potential inhibitors for invasive behaviors of human lung
      adenocarcinoma cells and disclosed the possible mechanisms. The association
      between structural features and anti-invasive activity of these compounds cannot
      be determined here and needs to be further verified.

PMID- 23560440
TI  - Spectrum-based method to generate good decoy libraries for spectral library
      searching in peptide identifications.
AB  - As spectral library searching has received increasing attention for peptide
      identification, constructing good decoy spectra from the target spectra is the
      key to correctly estimating the false discovery rate in searching against the
      concatenated target-decoy spectral library. Several methods have been proposed to
      construct decoy spectral libraries. Most of them construct decoy peptide
      sequences and then generate theoretical spectra accordingly. In this paper, we
      propose a method, called precursor-swap, which directly constructs decoy spectral
      libraries directly at the "spectrum level" without generating decoy peptide
      sequences by swapping the precursors of two spectra selected according to a very
      simple rule. Our spectrum-based method does not require additional efforts to
      deal with ion types (e.g., a, b or c ions), fragment mechanism (e.g., CID, or
      ETD), or unannotated peaks, but preserves many spectral properties. The precursor
      swap method is evaluated on different spectral libraries and the results of
      obtained decoy ratios show that it is comparable to other methods. Notably, it is
      efficient in time and memory usage for constructing decoy libraries. A software
      tool called Precursor-Swap-Decoy-Generation (PSDG) is publicly available for
      download at http://ms.iis.sinica.edu.tw/PSDG/.

PMID- 23560441
TI  - 6q deletion detected by fluorescence in situ hybridization using bacterial
      artificial chromosome in chronic lymphocytic leukemia.
AB  - Deletions of the long arm of chromosome 6 are known to occur at relatively low
      frequency (3-6%) in chronic lymphocytic leukemia (CLL), and they are more
      frequently observed in 6q21. Few data have been reported regarding other bands on
      6q involved by cytogenetic alterations in CLL. The cytogenetic study was
      performed in nuclei and metaphases obtained after stimulation with a combination
      of CpG-oligonucleotide DSP30 and interleukin-2. Four bacterial artificial
      chromosome (BAC) clones mapping regions in bands 6q16, 6q23, 6q25, 6q27 were used
      as probes for fluorescence in situ hybridization in 107 CLL cases in order to
      analyze the occurrence and localization of 6q aberrations. We identified 11 cases
      (10.2%) with 6q deletion of 107 patients studied with CLL. The trends of survival
      curves and the treatment-free intervals (TFI) of patients with deletion suggest a
      better outcome than the other cytogenetic risk groups. We observed two subgroups
      with 6q deletion as the sole anomaly: two cases with 6q16 deletion, and three
      cases with 6q25.2-27 deletion. There were differences of age, stage, and TFI
      between both subgroups. By using BAC probes, we observed that 6q deletion has a
      higher frequency in CLL and is linked with a good prognosis. In addition, it was
      observed that the deletion in 6q16 appears to be the most frequent and, if
      present as the only abnormality, it could be associated with a most widespread
      disease.

PMID- 23560442
TI  - Enhancing Raman scattering without plasmons: unprecedented sensitivity achieved
      by TiO2 shell-based resonators.
AB  - A remarkable enhancement of Raman scattering is achieved by TiO2 shell-based
      spherical resonators in the absence of plasmonic enhancers. This effect is
      ascribed to the synergistic combination of high refractive index of the shell
      layer, multiple light scattering through the spheres, and related geometrical
      factors and can be exploited to fabricate a new generation of self-diagnostic,
      recyclable SERS-active substrates.

PMID- 23560443
TI  - Inhibition of Glutaminyl Cyclases alleviates CCL2-mediated inflammation of non
      alcoholic fatty liver disease in mice.
AB  - Inflammation is an integral part of non-alcoholic fatty liver disease (NAFLD),
      the most prevalent form of hepatic pathology found in the general population. In
      this context, recently we have examined the potential role of Glutaminyl Cyclases
      (QC and isoQC), and their inhibitors, in the maturation of chemokines, for
      example, monocyte chemoattractant protein 1 (MCP-1, CCL2), to generate their
      bioactive conformation. Catalysis by isoQC leads to the formation of an N
      terminal pyroglutamate residue protecting CCL2 against degradation by
      aminopeptidases. This is of importance because truncated forms possess a reduced
      potential to attract immune cells. Since liver inflammation is characterized by
      the up-regulation of different chemokine pathways, and within this CCL2 is known
      to be a prominent example, we hypothesised that application of QC/isoQC
      inhibitors may alleviate liver inflammation by destabilizing CCL2. Therefore, we
      investigated the role of QC/isoQC inhibition, in comparison with the angiotensin
      receptor blocker Telmisartan, during development of pathology in a mouse model of
      non-alcoholic fatty liver disease. Application of a QC/isoQC inhibitor led to a
      significant reduction in circulating alanine aminotransferase and NAFLD activity
      score accompanied by an inhibitory effect on hepatocyte ballooning. Further
      analysis revealed a specific reduction of inflammation by decreasing the number
      of F4/80-positive macrophages, which is in agreement with the proposed CCL2
      related mechanism of action of QC/isoQC inhibitors. Finally, QC/isoQC inhibitor
      application attenuated liver fibrosis as characterized by reduced collagen
      deposition in the liver parenchyma. Thus in conclusion, QC/isoQC inhibitors are a
      promising novel class of anti-non-alcoholic steatohepatitis drugs which have a
      comparable disease-modifying effect to that of Telmisartan, which is probably
      mediated via specific interference with a comparable monocyte/macrophage
      infiltration that occurs under inflammatory conditions.

PMID- 23560444
TI  - Parent of origin influences the cardiac expression of vascular endothelial growth
      factor (Vegfa).
AB  - BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major regulator of
      both physiological and pathological angiogenesis. Associations between
      polymorphisms in VEGFA and complex disease have been inconsistent. The parent
      from whom the allele was inherited may account for these inconsistencies. This
      study examined the parent of origin effect on the expression of murine Vegfa.
      METHODS: Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were
      crossed to produce reciprocal AJ129 and 129AJ offspring, respectively. RNA was
      extracted from cardiac tissue of 6 week old male (n = 8) and female (n = 8)
      parental, and male and female F1 offspring mice (AJ129 n = 8 and 129AJ n = 8).
      Vegfa and Hif1a expression levels were measured by qPCR and compared between the
      F1 offspring from the reciprocal crosses. RESULTS: We found significant
      differences in the expression of Vegfa in F1 offspring (AJ129 and 129AJ mice) of
      the reciprocal crosses between AJ and 129 mice. Offspring of male AJ mice had
      significantly higher expression of Vegfa than offspring of male 129 mice (p =
      0.006). This difference in expression was not the result of preferential allele
      expression (allelic imbalance). Expression of Hif1a, a transcriptional regulator
      of Vegfa expression, was also higher in F1 offspring of an AJ father (p = 0.004).
      CONCLUSION: Differences in Vegfa and Hif1a gene expression are likely the result
      of an upstream angiogenic regulator gene that is influenced by the parent of
      origin. These results highlight the importance of including inheritance
      information, such as parent of origin, when undertaking allelic association
      studies.

PMID- 23560446
TI  - Carnitine palmitoyl transferase deficiency--unrecognized cause of recurrent acute
      kidney injury.
AB  - Metabolic myopathies represent a small percentage of rhabdomyolysis causes that
      could lead to acute kidney injury (AKI). This could be prevented if this
      condition is suspected and timely treated. Carnitine palmityl transferase (CPT)
      deficiency is the most frequent metabolic myopathy and should be considered
      whenever recurrent myoglobinuria is suspected, and distinguished from the second
      frequent one, McArdle disease. We present a case of a patient with two medically
      misinterpreted episodes of AKI in whom the subsequent diagnosis of CPT deficiency
      was established based on high index of clinical suspicion and correlation of
      clinical manifestations to specific metabolic defects. Application of simple
      measures and lifestyle changes improved our patient's life quality and prevented
      potential new life-threatening complications.

PMID- 23560447
TI  - Graphene MEMS: AFM probe performance improvement.
AB  - We explore the feasibility of growing a continuous layer of graphene in
      prepatterned substrates, like an engineered silicon wafer, and we apply this as a
      mold for the fabrication of AFM probes. This fabrication method proves the
      fabrication of SU-8 devices coated with graphene in a full-wafer parallel
      technology and with high yield. It also demonstrates that graphene coating
      enhances the functionality of SU-8 probes, turning them conductive and more
      resistant to wear. Furthermore, it opens new experimental possibilities such as
      studying graphene-graphene interaction at the nanoscale with the precision of an
      AFM or the exploration of properties in nonplanar graphene layers.

PMID- 23560448
TI  - Can excessive breastfeeding be the cause for the upside-down rotation of a breast
      implant? A case report.

PMID- 23560450
TI  - Longitudinal changes in breastfeeding patterns from 1 to 6 months of lactation.
AB  - OBJECTIVE: The most common reason given for discontinuation of exclusive
      breastfeeding is perceived insufficient milk supply. Breastfed infants show more
      variation in feeding frequency than bottle-fed infants, and this may lead to a
      mother lacking confidence in her milk supply if the frequency of breastfeeding
      sessions does not match expectations based on bottle feeding. We aimed to assist
      clinicians in supporting breastfeeding mothers by providing evidence-based
      information on expected changes in breastfeeding patterns and milk intake during
      exclusive breastfeeding for 6 months. SUBJECTS AND METHODS: Mothers and their
      healthy infants who were exclusively breastfeeding (total 24-hour milk intake
      within the normal range) were studied during two to five 24-hour periods between
      1 and 6 months of lactation. RESULTS: Between 1 and 3 months of lactation, the
      frequency of breastfeeding sessions decreased, whereas both the median and
      maximum breastmilk intakes during each breastfeeding session increased. These
      parameters remained constant between 3 and 6 months. The duration of each
      breastfeeding session decreased steadily from 1 to 6 months, but the total 24
      hour milk intake remained constant. CONCLUSIONS: Breastfeeding becomes more
      efficient between 1 and 3 months of lactation, although milk intake remains
      constant. Clinicians can give mothers confidence that these changes in
      breastfeeding behavior do not indicate insufficient milk supply, but may be a
      result of the increase in the stomach capacity of the infants and are an expected
      outcome of a healthy, normal breastfeeding relationship.

PMID- 23560449
TI  - Breastfeeding attitudes: association between maternal and male partner attitudes
      and breastfeeding intent.
AB  - Breastfeeding is considered the best infant feeding method, yet initiation and
      duration rates in the United States are lower than recommended by medical and
      public health professionals. Positive attitudes toward breastfeeding of the male
      partner are important in a mother's success at initiating and maintaining
      breastfeeding. This study measured the infant feeding attitudes of low-income
      women and their male partners using the Iowa Infant Feeding Attitude Scale
      (IIFAS), investigated the reliability and validity of the measure in male
      partners, and examined the associations of the partner's attitudes with the
      mother's attitudes and intention to breastfeed. A convenience sample of 112
      pregnant women and their male partners completed a survey including
      sociodemographic items, the IIFAS, and their intended infant feeding method in
      the hospital and in the first few weeks after the infant's birth (breastfeeding,
      formula feeding, mixed, and don't know). Mother's and partner's IIFAS scores were
      highly correlated, and higher scores of both mothers and partners were
      significantly associated with their intentions to breastfeed. With each increased
      point on mother's and partner's IIFAS scores, the odds that the mother and her
      partner intended to breastfeed in the first few weeks increased 12% and 20%,
      respectively. This is the first U.S. study to validate the IIFAS with male
      partners. Future research on breastfeeding attitudes and attitude-changing
      interventions is needed to see if improving partners' attitudes toward
      breastfeeding will also improve mothers' attitudes and if that increases
      initiation and duration of breastfeeding.

PMID- 23560451
TI  - Linking isoprenoidal GDGT membrane lipid distributions with gene abundances of
      ammonia-oxidizing Thaumarchaeota and uncultured crenarchaeotal groups in the
      water column of a tropical lake (Lake Challa, East Africa).
AB  - Stratified lakes are important reservoirs of microbial diversity and provide
      habitats for niche differentiation of Archaea. In this study, we used a lipid
      biomarker/DNA-based approach to reveal the diversity and abundance of Archaea in
      the water column of Lake Challa (East Africa). Concentrations of intact polar
      lipid (IPL) crenarchaeol, a specific biomarker of Thaumarchaeota, were enhanced
      (1 ng l(-1) ) at the oxycline/nitrocline. The predominance of the more labile IPL
      hexose-phosphohexose crenarchaeol indicated the presence of an actively living
      community of Thaumarchaeota. Archaeal 16S rRNA clone libraries revealed the
      presence of thaumarchaeotal groups 1.1a and 1.1b at and above the oxycline. In
      the anoxic deep water, amoA gene abundance was an order of magnitude lower than
      at the oxycline and high abundance (~90 ng l(-1) ) of an IPL with the acyclic
      glycerol dialkyl glycerol tetraether (GDGT-0) was evident. The predominance of
      archaeal 16S rRNA sequences affiliated to the uncultured crenarchaeota groups 1.2
      and miscellaneous crenarchaeotic group (MCG) points to an origin of GDGT-0 from
      uncultured crenarchaeota. This study demonstrates the importance of thermal
      stratification and nutrient availability in the distribution of archaeal groups
      in lakes, which is relevant to constrain and validate temperature proxies based
      on archaeal GDGTs (i.e. TEX86 ).

PMID- 23560452
TI  - Hemlock woolly adelgid (Adelges tsugae) infestation affects water and carbon
      relations of eastern hemlock (Tsuga canadensis) and Carolina hemlock (Tsuga
      caroliniana).
AB  - Hemlock woolly adelgid (HWA) is an exotic insect pest causing severe decimation
      of native hemlock trees. Extensive research has been conducted on the ecological
      impacts of HWA, but the exact physiological mechanisms that cause mortality are
      not known. Water relations, anatomy and gas exchange measurements were assessed
      on healthy and infested eastern (Tsuga canadensis) and Carolina (Tsuga
      caroliniana) hemlock trees. These data were then used in a mechanistic model to
      test whether the physiological responses to HWA infestation were sufficiently
      significant to induce changes in whole-plant water use and carbon uptake. The
      results indicated coordinated responses of functional traits governing water
      relations in infested relative to healthy trees. In response to HWA, leaf water
      potential, carbon isotope ratios, plant hydraulic properties and stomatal
      conductance were affected, inducing a reduction in tree water use by > 40% and
      gross primary productivity by 25%. Anatomical changes also appeared, including
      the activation of traumatic cells. HWA infestation had a direct effect on plant
      water relations. Despite some leaf compensatory mechanisms, such as an increase
      in leaf hydraulic conductance and nitrogen content, tree water use and carbon
      assimilation were diminished significantly in infested trees, which could
      contribute to tree mortality.

PMID- 23560453
TI  - Investigation of the structure and spectroscopy of H5(+) using diffusion Monte
      Carlo.
AB  - The results of diffusion Monte Carlo (DMC) calculations of the ground and
      selected excited states of H5(+) and its deuterated analogues are presented.
      Comparisons are made between the results obtained from two recently reported
      potential surfaces. Both of these surfaces are based on CCSD(T) electronic
      energies, but the fits display substantial differences in the energies of low
      lying stationary points. Little sensitivity to these features is found in the DMC
      results, which yield zero-point energies based on the two surfaces that differ by
      between 20 and 30 cm(-1) for all twelve isotopologues of H5(+). Likewise,
      projections of the ground state probability amplitudes, evaluated for the two
      surfaces, are virtually identical. By using the ground state probability
      amplitudes, vibrationally averaged rotational constants and dipole moments were
      calculated. On the basis of these calculations, all isotopologues are shown to be
      near-prolate symmetric tops. Further, in cases where the ion had a nonzero dipole
      moment, the magnitude of the vibrationally averaged dipole moment was found to
      range from 0.33 to 1.15 D, which is comparable to the dipole moments of H2D+ and
      HD2(+). Excited states with up to three quanta in the shared proton stretch and
      one quantum in the in-phase stretch of the outer H2 groups were also
      investigated. Trends in the energies and the properties of these states are
      discussed.

PMID- 23560454
TI  - Effects of intra-operative ketamine administration on postoperative catheter
      related bladder discomfort: a double-blind clinical trial.
AB  - PURPOSE: Urinary catheterization during surgery frequently leads to unfavorable
      signs and symptoms (ie urgency, discomfort, frequency) during recovery. These
      signs and symptoms are collectively called catheter-related bladder discomfort
      (CRBD). We hypothesized that preemptive IV ketamine administration prior to intra
      operative catheterization would reduce the incidence of CRBD in the postoperative
      period when compared to placebo. METHODS: The study consisted of 114 adult
      patients undergoing elective nephrectomy. They were randomized to 2 equal groups
      of 57 subjects. In the intervention group, IV ketamine (0.5 mg/kg) was
      administered directly after induction of anesthesia, but before urinary
      catheterization. The control group received an injection of 2 mL of normal
      saline. The study evaluated the incidence and severity of CRBD at 0, 1, 2, and 6
      hours after commencement of the recovery period. The study also compared the
      incidence of postoperative nausea and vomiting, hallucinations, sedation, and
      respiratory depression in the 2 groups. RESULTS: At the 0- and 1-hour
      evaluations, the incidence and severity of CRBD were lower in the intervention
      group; however, at the 2- and 6-hour evaluations, there were no significant
      differences in incidence and severity of CRBD between the 2 groups. A decreased
      incidence of postoperative nausea and vomiting (PONV) was observed at 2- and 6
      hour visits in the intervention group. Also, a higher occurrence of sedation was
      seen at the 0-hour checkup in the intervention group. CONCLUSION: Preemptive
      administration of IV ketamine (0.5 mg/kg) can reduce incidence and severity of
      CRBD in the early postoperative period.

PMID- 23560455
TI  - Antiproliferative effect of pheophorbide a-mediated photodynamic therapy and its
      synergistic effect with doxorubicin on multiple drug-resistant uterine sarcoma
      cell MES-SA/Dx5.
AB  - Prolonged cancer chemotherapy is associated with the development of multidrug
      resistance (MDR), which is a major cause of treatment failure. Photodynamic
      therapy (PDT) has been applied as anticancer therapy and a means of circumventing
      MDR. The antiproliferative effect of pheophorbide a-mediated photodynamic therapy
      (Pa-PDT) has been demonstrated in several human cancer cell lines, including the
      uterine sarcoma cell line, MES-SA. This study set out to evaluate, first, the
      therapeutic potential of Pa-PDT on MES-SA/Dx5 uterine sarcoma cells and,
      subsequently, the effectiveness of combination therapy using Pa-PDT with
      doxorubicin (Dox). Our results showed that Pa-PDT was able to circumvent MDR in
      the P-glycoprotein (P-gp) overexpressing human uterine sarcoma cell line, MES
      SA/Dx5. Intracellular accumulation of Pa and Pa-PDT-induced cell death was not
      abrogated by MDR phenotype, when compared to the parental cell line, MES-SA.
      Combined therapy using Pa-PDT and Dox, a common chemotherapeutic drug, was found
      to be synergistic in the cell line, MES-SA/Dx5. Both activity and expression of
      MDR1 and P-gp were reduced by Pa-PDT treatment and such reductions were
      attenuated by alpha-tocopherol, the scavenger of reactive oxygen species (ROS),
      suggesting that the effect of Pa-PDT was mediated by the generation of
      intracellular ROS. In conclusion, our findings demonstrated the therapeutic
      potential of Pa-PDT alone or in combination with Dox in combating multidrug
      resistant malignancies.

PMID- 23560456
TI  - Tissue factor activity and ECM-related gene expression in human aortic
      endothelial cells grown on electrospun biohybrid scaffolds.
AB  - All blood vessels are lined with a quiescent endothelium, which aids in
      regulating regular blood flow and avoiding thrombus formation. Current attempts
      at replacing diseased blood vessels frequently fail due to the intrinsic
      thrombogenicity of the materials used as vascular grafts. In extending our
      previous work where we introduced a new candidate scaffolds for vascular grafts
      electrospun from a blend solution of PLGA, gelatin, and elastin (PGE), this study
      aimed to evaluate the potential of PGE scaffolds to support nonthrombogenic
      monolayers of primary isolates of human aortic endothelial cells (HAECs), as
      assessed by a combination of biochemical, molecular, and bioinformatics-based
      analyses. After 24 h of culture on 3-D fibrous PGE scaffolds, HAECs formed a
      confluent, nonthrombogenic, and physiologically competent monolayer, as assessed
      by tissue factor (TF) gene expression and protein activity assays. The levels of
      TF mRNA/protein activity in HAECs grown on PGE scaffolds were similar to those on
      gelatin or collagen IV-coated 2-D surfaces. In addition, bioinformatics-based
      analysis of a focused microarray containing 84 ECM-related cDNA probes
      demonstrated that HAECs essentially expressed a histotypic ECM-related
      "transcriptome" on PGE scaffolds, where cells were more quiescent than cells
      cultured on 2-D coverslips coated with gelatin (a well-known "inert" substrate
      for conventional EC culture), but less so than on 2-D PGE films. These data
      suggest an important role for nanorough substrates (PGE films) in passivating
      endothelial cells and confirm the crucial effect of substrate composition in this
      process. Principal component analysis of microarray data on the above substrates
      (including collagen IV) implied that substrate composition plays a greater role
      than surface topography in affecting the endothelial ECM-related "transcriptome".
      Taken together, our findings suggest that electrospun PGE scaffolds are
      potentially suitable for application in small diameter vascular tissue
      engineering.

PMID- 23560458
TI  - Other inflammatory markers should be kept in mind when assessing the mean
      platelet volume.

PMID- 23560457
TI  - Fabrication and evaluation of osteoblastic differentiation of human mesenchymal
      stem cells on novel CaO-SiO2-P2O5-B2O3 glass-ceramics.
AB  - Apatite-wollastonite glass-ceramics have high mechanical strength, and CaO-SiO2 
      B2 O3 glass-ceramics showed excellent bioactivity and high biodegradability. A
      new type of CaO-SiO2 -P2 O5 -B2 O3 system of bioactive glass-ceramics (BGS-7) was
      fabricated, and the effect and usefulness was evaluated via bioactivity using
      simulated body fluid and human mesenchymal stem cells (hMSCs). The purpose of
      this study was to compare BGS-7 and hydroxyapatite (HA) using hMSCs in order to
      evaluate the bioactivity of BGS-7 and its possibility as a bone graft extender.
      Alkaline phosphatase (ALP) staining, ALP activity, cell proliferation 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium, inner salt (MTS) assay, Alizarin Red-S (AR-S) staining, calcium
      levels, the mRNA expression of ALP, osteocalcin, osteopontin, and runt-related
      transcription factor 2 (runx-2) using reverse-transcription polymerase chain
      reaction (RT-PCR) and the protein expression of osteocalcin and runx-2 using
      Western blot were measured by transplanting hMSC onto a tissue culture plate, HA,
      and BGS-7. The ALP staining and AR-S staining of BGS-7 was greater than that of
      HA and control. The ALP value of BGS-7 was significantly higher than that of HA
      and control. The MTS results showed that BGS-7 had a higher value than the groups
      transplanted onto HA and control on day 15. The calcium level was higher than the
      control in both HA and BGS-7, and was especially high in BGS-7. There were more
      mineral products on BGS-7 than on the HA when analyzed by scanning electron
      microscopy. The mRNA expression of ALP, osteopontin, osteocalcin, and runx-2 were
      higher on BGS-7 than on HA and the control when analyzed by RT-PCR. The relative
      gene expression of osteopontin and runx-2 were found to be higher on BGS-7 than
      on HA and the control by Western blot. Accordingly, it is predicted that BGS-7
      would have high biocompatibility and good osteoconductivity, and presents a
      possibility as a new bone graft extender. 

PMID- 23560459
TI  - Evolution of ultrathin endoscope.

PMID- 23560460
TI  - Diffusion pattern of low dose rate brachytherapy for prostate cancer in Japan.
AB  - Permanent implant brachytherapy for prostate cancer using iodine-125 seeds was
      adopted in Japan in 2003. Here, we report on the diffusion pattern of this
      treatment in Japan since 2003. We examined the annual numbers of prostate cancer
      patients per hospital in Japan, who were treated with iodine-125 seed implant
      brachytherapy with or without external beam radiation therapy between 2003 and
      2011. The hospitals were excluded from the count if brachytherapy was begun in a
      hospital within the given year, and thus was only available for part of the year.
      In 2004, 269 patients were treated by brachytherapy at only two hospitals.
      However, the numbers increased rapidly. A total of 1412 patients were treated at
      23 hospitals in 2005, 2783 patients were treated at 83 hospitals in 2008, and
      3793 patients were treated at 109 hospitals in 2011. The mean/median numbers of
      patients treated per hospital were 61.4/42 in 2005, 33.5/25 in 2008, and 35.0/24
      in 2011. The number of hospitals where 24 or fewer patients were treated in a
      year increased. On the other hand, the number of hospitals with a volume of >48
      patients per year was stable. Because a relationship between provider volume and
      outcomes following oncological procedures was shown, a careful evaluation of the
      effectiveness of permanent implant brachytherapy for prostate cancer is needed. 

PMID- 23560461
TI  - Application of Bayesian population physiologically based pharmacokinetic (PBPK)
      modeling and Markov chain Monte Carlo simulations to pesticide kinetics studies
      in protected marine mammals: DDT, DDE, and DDD in harbor porpoises.
AB  - Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a
      challenge because of the lack of parameter information and the ban on exposure
      experiments. To minimize uncertainty and variability, parameter estimation
      methods are required for the development of reliable PBPK models. The present
      study is the first to develop PBPK models for the lifetime bioaccumulation of
      p,p'-DDT, p,p'-DDE, and p,p'-DDD in harbor porpoises. In addition, this study is
      also the first to apply the Bayesian approach executed with Markov chain Monte
      Carlo simulations using two data sets of harbor porpoises from the Black and
      North Seas. Parameters from the literature were used as priors for the first
      "model update" using the Black Sea data set, the resulting posterior parameters
      were then used as priors for the second "model update" using the North Sea data
      set. As such, PBPK models with parameters specific for harbor porpoises could be
      strengthened with more robust probability distributions. As the science and
      biomonitoring effort progress in this area, more data sets will become available
      to further strengthen and update the parameters in the PBPK models for harbor
      porpoises as a species anywhere in the world. Further, such an approach could
      very well be extended to other protected marine mammals.

PMID- 23560462
TI  - PPAR alpha: a novel radiation target in locally exposed Mus musculus heart
      revealed by quantitative proteomics.
AB  - Radiation exposure of the thorax is associated with a markedly increased risk of
      cardiac morbidity and mortality with a latency period of decades. Although many
      studies have confirmed the damaging effect of ionizing radiation on the
      myocardium and cardiac endothelial structure and function, the molecular
      mechanism behind this damage is not yet elucidated. Peroxisome proliferator
      activated receptor alpha (PPAR alpha), a transcriptional regulator of lipid
      metabolism in heart tissue, has recently received great attention in the
      development of cardiovascular disease. The goal of this study was to investigate
      radiation-induced cardiac damage in general and the role of PPAR alpha in this
      process in particular. C57BL/6 mice received local heart irradiation with X-ray
      doses of 8 and 16 gray (Gy) at the age of 8 weeks. The mice were sacrificed 16
      weeks later. Radiation-induced changes in the cardiac proteome were quantified
      using the Isotope Coded Protein Label (ICPL) method followed by mass spectrometry
      and software analysis. Significant alterations were observed in proteins involved
      in lipid metabolism and oxidative phosphorylation. Ionizing radiation markedly
      changed the phosphorylation and ubiquitination status of PPAR alpha. This was
      reflected as decreased expression of its target genes involved in energy
      metabolism and mitochondrial respiratory chain confirming the proteomics data.
      This study suggests that persistent alteration of cardiac metabolism due to
      impaired PPAR alpha activity contributes to the heart pathology after radiation.

PMID- 23560463
TI  - Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis:
      histology, Epstein-Barr virus, and clonality are important predictors of disease
      progression and regression.
AB  - OBJECTIVES: Patients with rheumatoid arthritis (RA) may develop
      lymphoproliferative disorders (RA-LPD). Immunosuppressive states due to
      methotrexate (MTX) and Epstein-Barr virus (EBV) reactivation have been regarded
      as causes. Sometimes spontaneous regression occurs after withdrawal of MTX. The
      objective of this study was to identify factors predictive of relapse and
      survival in patients with RA-LPD, and spontaneous regression in patients with RA
      LPD treated with MTX (MTX-LPD). METHODS: We evaluated the clinicopathological
      features, clinical characteristics, and treatment outcomes in 102 cases of RA
      LPD. In addition, EBV infection and clonality of immunoglobulin heavy chain gene
      (IGH) were analyzed by in situ hybridization and polymerase chain reaction,
      respectively. RESULTS: The 102 cases included patients with diffuse large B-cell
      lymphoma (DLBCL; n = 53), Hodgkin lymphoma (n = 9), polymorphic B-cell LPD (n =
      20), reactive lymphadenitis (n = 11), peripheral T-cell lymphoma (PTCL; n = 4),
      composite lymphoma (n = 2), and follicular lymphoma (n = 3). EBV was detected in
      60% (56/93) of patients. Spontaneous regression occurred in 59% (28/47) of
      patients in whom MTX was withdrawn. Regression was associated with EBV positivity
      (P = 0.007) and non-DLBCL (P = 0.006), but not with MTX amount and other clinical
      features. Monoclonal bands of IGH were observed in 31 of 74 cases. In patients
      with DLBCL, poor disease-free survival (P = 0.05) was associated with clonality
      of IGH. In all patients, factors predictive of shorter survival were age (>70 yr)
      and histological type of DLBCL. CONCLUSIONS: Histology, EBV positivity, and
      monoclonality of IGH are useful for predicting clinical outcomes in patients with
      RA-LPD.

PMID- 23560464
TI  - Detecting chronic kidney disease in population-based administrative databases
      using an algorithm of hospital encounter and physician claim codes.
AB  - BACKGROUND: Large, population-based administrative healthcare databases can be
      used to identify patients with chronic kidney disease (CKD) when serum creatinine
      laboratory results are unavailable. We examined the validity of algorithms that
      used combined hospital encounter and physician claims database codes for the
      detection of CKD in Ontario, Canada. METHODS: We accrued 123,499 patients over
      the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine
      value to estimate glomerular filtration rate (eGFR). We developed an algorithm of
      physician claims and hospital encounter codes to search administrative databases
      for the presence of CKD. We determined the sensitivity, specificity, positive and
      negative predictive values of this algorithm to detect our primary threshold of
      CKD, an eGFR <45 mL/min per 1.73 m2 (15.4% of patients). We also assessed serum
      creatinine and eGFR values in patients with and without CKD codes (algorithm
      positive and negative, respectively). RESULTS: Our algorithm required evidence of
      at least one of eleven CKD codes and 7.7% of patients were algorithm positive.
      The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%].
      Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in
      the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All
      specificities were over 94%. The positive and negative predictive values were
      65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In
      algorithm positive patients, the median [interquartile range (IQR)] baseline
      serum creatinine value was 135 MUmol/L (106 to 179 MUmol/L) compared to 82
      MUmol/L (69 to 98 MUmol/L) for algorithm negative patients. Corresponding eGFR
      values were 38 mL/min per 1.73 m2 (26 to 51 mL/min per 1.73 m2) vs. 69 mL/min per
      1.73 m2 (56 to 82 mL/min per 1.73 m2), respectively. CONCLUSIONS: Patients with
      CKD as identified by our database algorithm had distinctly higher baseline serum
      creatinine values and lower eGFR values than those without such codes. However,
      because of limited sensitivity, the prevalence of CKD was underestimated.

PMID- 23560465
TI  - Development of the knowledge-based and empirical combined scoring algorithm
      (KECSA) to score protein-ligand interactions.
AB  - We describe a novel knowledge-based protein-ligand scoring function that employs
      a new definition for the reference state, allowing us to relate a statistical
      potential to a Lennard-Jones (LJ) potential. In this way, the LJ potential
      parameters were generated from protein-ligand complex structural data contained
      in the Protein Databank (PDB). Forty-nine (49) types of atomic pairwise
      interactions were derived using this method, which we call the knowledge-based
      and empirical combined scoring algorithm (KECSA). Two validation benchmarks were
      introduced to test the performance of KECSA. The first validation benchmark
      included two test sets that address the training set and enthalpy/entropy of
      KECSA. The second validation benchmark suite included two large-scale and five
      small-scale test sets, to compare the reproducibility of KECSA, with respect to
      two empirical score functions previously developed in our laboratory (LISA and
      LISA+), as well as to other well-known scoring methods. Validation results
      illustrate that KECSA shows improved performance in all test sets when compared
      with other scoring methods, especially in its ability to minimize the root mean
      square error (RMSE). LISA and LISA+ displayed similar performance using the
      correlation coefficient and Kendall tau as the metric of quality for some of the
      small test sets. Further pathways for improvement are discussed for which would
      allow KECSA to be more sensitive to subtle changes in ligand structure.

PMID- 23560466
TI  - Pressure modulation of Ras-membrane interactions and intervesicle transfer.
AB  - Proteins attached to the plasma membrane frequently encounter mechanical
      stresses, including high hydrostatic pressure (HHP) stress. Signaling pathways
      involving membrane-associated small GTPases (e.g., Ras) have been identified as
      critical loci for pressure perturbation. However, the impact of mechanical
      stimuli on biological outputs is still largely terra incognita. The present study
      explores the effect of HHP on the membrane association, dissociation, and
      intervesicle transfer process of N-Ras by using a FRET-based assay to obtain the
      kinetic parameters and volumetric properties along the reaction path of these
      processes. Notably, membrane association is fostered upon pressurization.
      Conversely, depending on the nature and lateral organization of the lipid
      membrane, acceleration or retardation is observed for the dissociation step. In
      addition, HHP can be inferred as a positive regulator of N-Ras clustering, in
      particular in heterogeneous membranes. The susceptibility of membrane interaction
      to pressure raises the idea of a role of lipidated signaling molecules as
      mechanosensors, transducing mechanical stimuli to chemical signals by regulating
      their membrane binding and dissociation. Finally, our results provide first
      insights into the influence of pressure on membrane-associated Ras-controlled
      signaling events in organisms living under extreme environmental conditions such
      as those that are encountered in the deep sea and sub-seafloor environments,
      where pressures reach the kilobar (100 MPa) range.

PMID- 23560467
TI  - Use of the air-Q intubating laryngeal airway for rapid-sequence intubation in
      infants with severe airway obstruction: a case series.
AB  - We describe a four-step method for fibreoptic-guided, rapid-sequence tracheal
      intubation through the air-Q intubating laryngeal airway in infants with severe
      airway obstruction. Our step-wise process provides an organised and controlled
      approach to safely securing the airway.

PMID- 23560470
TI  - Memory effect in a topological surface state of Bi2Te2Se.
AB  - We demonstrate the controllable local manipulation of the Dirac surface state in
      a topological insulator, Bi2Te2Se, which has suppressed bulk carrier density.
      Using scanning tunneling microscopy/spectroscopy under magnetic fields, we
      observe Landau levels of the Dirac surface state in the conductance spectra. The
      Landau levels start to shift in their energy once the bias voltage between the
      tip and the sample exceeds a threshold value. The amount of shift depends on the
      history of bias ramping. As a result, conductance spectra show noticeable
      hysteresis, giving rise to a memory effect. The conductance images exhibit
      spatially inhomogeneous patterns which can also be controlled by the bias voltage
      in a reproducible way. On the basis of these observations, we argue that the
      memory effect is associated with the tip-induced local charging effect which is
      pinned by the defect-generated random potential. Our study opens up a new avenue
      to controlling the topological surface state.

PMID- 23560469
TI  - Amlodipine increases vitamin D levels more than valsartan in newly diagnosed
      hypertensive patients: pointing to an additional effect on bone metabolism or a
      novel marker of inflammation?
AB  - Hypertension is a major challenge for public health. Appropriate antihypertensive
      treatment seem to provide a better life with lower morbidity and mortality rates.
      Another pathologic condition, osteoporosis, mainly affects postmenouposal women,
      and constitutes a growing body of risks after a particular age. As bone is a
      dynamic organ system that is directly related to calcium and phosphor metabolism,
      imbalance in these two parameters upon aging or menopause finally may lead to
      osteoporosis. Today, both osteoporosis and high blood pressure are major
      morbidities, especially in the elderly population. There are some intriguing
      results on the effects of antihypertensive agents on bone metabolism in the
      literature. In this study, we aimed to investigate the effects of widely used
      antihypertensive agents, valsartan and amlodipine on vitamin D levels in newly
      diagnosed hypertensive population. We found that amlodipine increased vitamin D
      levels significantly in patients with a newly diagnosed hypertension on a 12-week
      treatment duration compared to valsartan.

PMID- 23560471
TI  - Lowered serum total L-carnitine levels are associated with obesity at term
      pregnancy.
AB  - OBJECTIVE: This study aims to compare the serum total l-carnitine concentrations
      of obese and non-obese pregnant women and to identify the role of L-carnitine in
      both maternal and fetal weight gain during pregnancy. METHOD: This study reviews
      118 healthy women with singleton term pregnancy (>=37 weeks). The characteristics
      of the recruited subjects were analyzed according to their pre-pregnancy body
      mass index (BMI). RESULTS: The women with pre-pregnancy BMI < 18.5 kg/m(2) had
      significantly higher serum L-carnitine levels whereas the women with BMI > 29.9
      kg/m(2) at term pregnancy had significantly lower serum l-carnitine levels (p =
      0.001 for both). The neonates born to women with BMI > 29.9 kg/m(2) at term
      pregnancy had significantly longer height and wider head circumference (p = 0.001
      for both). Serum total L-carnitine levels correlated significantly and negatively
      with pre-pregnancy body weight, pre-pregnancy BMI, pregnancy body weight,
      pregnancy BMI and serum triglyceride levels (r = -0.397, p = 0.001; r = -0.357, p
      = 0.001; r = -0.460, p = 0.001; r = -0.463, p = 0.001 and r = -0.216, p = 0.019,
      respectively). There was a significant and positive correlation between L
      carnitine and HDL values (r = 0.243, p = 0.008). CONCLUSIONS: The crucial role of
      L-carnitine in pregnancy metabolism suggests that nutritional supplementation of
      this amino acid can be offered to women who are either overweight or obese at the
      beginning of the pregnancy.

PMID- 23560472
TI  - Allo- and xeno-reassembly of human and rat myometrium from cells and scaffolds.
AB  - Neo-myometrium was created by culturing isolated myocytes into decellularized rat
      and human myometrial scaffolds. The dual purpose of the uterus is to accommodate
      the growing fetus, and then expel the fetus at term by phasically contracting it.
      The first function requires physical robustness as well as the ability to expand
      and remodel. Congenital anomalies or previous surgeries can mechanically
      compromise the uterus and lead to major complications in pregnancy. The second
      function utilizes multiple interactions of complex physiological mechanisms that
      have yet to be fully elucidated, and this knowledge gap contributes to the
      continuation of serious complications of pregnancy. To address both problems, we
      reconstructed myometrium from isolated myocytes and scaffold. From both rat and
      human myometrium, myocytes were isolated using collagenase digestion, and
      scaffolds were isolated using ethanol/ trypsin protocols. The number of myocytes
      was amplified using monolayer culture, and then, the myocytes were cultured back
      into the scaffolds. We called this engineered tissue neo-myometrium, with allo
      neo-myometrium being made from components of the same species, and xeno-neo
      myometrium from across species. By artificially creating defects in rat scaffold,
      allo-neo-myometrium was created that demonstrated rapid scaffold remodeling. Xeno
      neo myometrium (human myocytes/rat scaffold) was created and demonstrated
      myocytes occurring in bundles 500 MUm deep in the scaffold. These experiments
      provide proof of principle that modest numbers of myocytes can be amplified and
      used to create a larger volume of engineered tissue, which may be useful for semi
      autologous transplantation to repair structural defects of the human uterus. In
      isometric contractility experiments, coordinated contractions were observed in
      xeno-neo-myometrium (human myocytes, rat scaffold), but not allo-neo-myometrium
      (human myocytes, human scaffold). 

PMID- 23560473
TI  - Breastfeeding may protect from developing attention-deficit/hyperactivity
      disorder.
AB  - INTRODUCTION: Breastfeeding has a positive influence on physical and mental
      development. Attention-deficit/hyperactivity disorder (ADHD) is a common
      neurobehavioral disorder with major social, familial, and academic influences.
      The present study aimed to evaluate whether ADHD is associated with a shorter
      duration of breastfeeding. SUBJECTS AND METHODS: In this retrospective matched
      study, children 6-12 years old diagnosed at Schneider's Children Medical Center
      (Petach Tikva, Israel) with ADHD between 2008 and 2009 were compared with two
      control groups. The first one consisted of healthy (no ADHD) siblings of ADHD
      children; the second control group consisted of children without ADHD who
      consulted at the otolaryngology clinic. A constructed questionnaire about
      demographic, medical, and perinatal findings, feeding history during the first
      year of life, and a validated adult ADHD screening questionnaire were given to
      both parents of every child in each group. RESULTS: In children later diagnosed
      as having ADHD, 43% were breastfed at 3 months of age compared with 69% in the
      siblings group and 73% in the control non-related group (p=0.002). By 6 months of
      age 29% of ADHD children were breastfed compared with 50% in the siblings group
      and 57% in the control non-related group (p=0.011). A stepwise logistic
      regression that included the variables found to be significant in univariate
      analysis demonstrated a significant association between ADHD and lack of
      breastfeeding at 3 months of age, maternal age at birth, male gender, and
      parental divorce. CONCLUSIONS: Children with ADHD were less likely to breastfeed
      at 3 months and 6 months of age than children in the two control groups. We
      speculate that breastfeeding may have a protective effect from developing ADHD
      later in childhood.

PMID- 23560474
TI  - Low-income inner-city fathers and breastfeeding--where's the program for us?

PMID- 23560475
TI  - Failure mode and effect analysis in blood transfusion: a proactive tool to reduce
      risks.
AB  - BACKGROUND: The aim of blood transfusion risk management is to improve the
      quality of blood products and to assure patient safety. We utilize failure mode
      and effect analysis (FMEA), a tool employed for evaluating risks and identifying
      preventive measures to reduce the risks in blood transfusion. STUDY DESIGN AND
      METHODS: The failure modes and effects occurring throughout the whole process of
      blood transfusion were studied. Each failure mode was evaluated using three
      scores: severity of effect (S), likelihood of occurrence (O), and probability of
      detection (D). Risk priority numbers (RPNs) were calculated by multiplying the S,
      O, and D scores. The plan-do-check-act cycle was also used for continuous
      improvement. RESULTS: Analysis has showed that failure modes with the highest
      RPNs, and therefore the greatest risk, were insufficient preoperative assessment
      of the blood product requirement (RPN, 245), preparation time before infusion of
      more than 30 minutes (RPN, 240), blood transfusion reaction occurring during the
      transfusion process (RPN, 224), blood plasma abuse (RPN, 180), and insufficient
      and/or incorrect clinical information on request form (RPN, 126). After
      implementation of preventative measures and reassessment, a reduction in RPN was
      detected with each risk. The failure mode with the second highest RPN, namely,
      preparation time before infusion of more than 30 minutes, was shown in detail to
      prove the efficiency of this tool. CONCLUSIONS: FMEA evaluation model is a useful
      tool in proactively analyzing and reducing the risks associated with the blood
      transfusion procedure.

PMID- 23560476
TI  - A randomized controlled study to compare the 2% lignocaine and aqueous
      lubricating gels for female urethral catheterization.
AB  - OBJECTIVE: The 2% lignocaine gel has long been used for male urethral
      catheterization, but aqueous gel as lubricant has been used for females. However,
      studies report that females experience pain during urethral catheterization. We
      compared the effectiveness of 2% lignocaine gel (intervention) and aqueous gel
      (control) for female urethral catheterization in reducing procedural pain.
      METHODS: A double-blinded, randomized controlled trial (RCT) was conducted from
      November 2011 to April 2012 in an acute care hospital in Singapore. In total, 52
      adult female inpatients (26 interventions vs. 26 controls) requiring urethral
      catheterization were included in the study. The intervention included patients
      receiving 2% lignocaine gel as a lubricant for urethral catheterization.
      Patients' pre- and postprocedural visual analog scale (VAS) were collected
      prospectively and nonparametric tests were used for data analysis. RESULTS: There
      was a significant reduction from the preprocedure pain score (Median = 22.0 mm)
      to the postprocedural pain score (Median = 6.6 mm) in the 2% lignocaine group (Z
      = -3.8, P < 0.001), but not in the aqueous gel group (pre vs. post: 16.5 mm vs.
      18.2 mm; Z = -0.36, P = 0.716). Subjects using 2% lignocaine gel had
      significantly more reduction in the postprocedural pain score than the aqueous
      gel group (U = 209.5, P = 0.019). CONCLUSIONS: The 2% lignocaine gel
      significantly reduces the procedural pain of female urethral catheterization as
      compared with aqueous gel. This study provides evidence for the hospital to
      change the current practice in the hope of reducing procedural pain for female
      patients during urethral catheterization.

PMID- 23560478
TI  - Suppression of intersite charge transfer in charge-disproportionated perovskite
      YCu3Fe4O12.
AB  - A novel iron perovskite YCu3Fe4O12 was synthesized under high pressure and high
      temperature of 15 GPa and 1273 K. Synchrotron X-ray and electron diffraction
      measurements have demonstrated that this compound crystallizes in the cubic
      AA'3B4O12-type perovskite structure (space group Im3, No. 204) with a lattice
      constant of a = 7.30764(10) A at room temperature. YCu3Fe4O12 exhibits a charge
      disproportionation of 8Fe(3.75+) -> 3Fe(5+) + 5Fe(3+), a ferrimagnetic ordering,
      and a metal-semiconductor-like transition simultaneously at 250 K, unlike the
      known isoelectronic compound LaCu3Fe4O12 that currently shows an intersite charge
      transfer of 3Cu(2+) + 4Fe(3.75+) -> 3Cu(3+) + 4Fe(3+), an antiferromagnetic
      ordering, and a metal-insulator transition at 393 K. This finding suggests that
      intersite charge transfer is not the only way of relieving the instability of the
      Fe(3.75+) state in the A(3+)Cu(2+)3Fe(3.75+)4O12 perovskites. Crystal structure
      analysis reveals that bond strain, rather than the charge account of the A-site
      alone, which is enhanced by large A(3+) ions, play an important role in
      determining which of intersite charge transfer or charge disproportionation is
      practical.

PMID- 23560477
TI  - Adaptive constructive processes and memory accuracy: consequences of
      counterfactual simulations in young and older adults.
AB  - People frequently engage in counterfactual thinking: mental simulations of
      alternative outcomes to past events. Like simulations of future events,
      counterfactual simulations serve adaptive functions. However, future simulation
      can also result in various kinds of distortions and has thus been characterised
      as an adaptive constructive process. Here we approach counterfactual thinking as
      such and examine whether it can distort memory for actual events. In Experiments
      1a/b young and older adults imagined themselves experiencing different scenarios.
      Participants then imagined the same scenario again, engaged in no further
      simulation of a scenario, or imagined a counterfactual outcome. On a subsequent
      recognition test participants were more likely to make false alarms to
      counterfactual lures than novel scenarios. Older adults were more prone to these
      memory errors than younger adults. In Experiment 2 younger and older participants
      selected and performed different actions, then recalled performing some of those
      actions, imagined performing alternative actions to some of the selected actions,
      and did not imagine others. Participants, especially older adults, were more
      likely to falsely remember counterfactual actions than novel actions as
      previously performed. The findings suggest that counterfactual thinking can cause
      source confusion based on internally generated misinformation, consistent with
      its characterisation as an adaptive constructive process. 

PMID- 23560479
TI  - Neurological complications during pulsatile ventricular assistance with the
      Berlin Heart EXCOR in children: incidence and risk factors.
AB  - The aim of this study is to describe the incidence of brain injury (BI) in
      children with end-stage cardiac failure who were supported with the Berlin Heart
      EXCOR ventricular assist device (VAD) as a bridge to heart transplantation.
      Between January 2002 and January 2012, all patients <18 years of age who
      underwent the implantation of the Berlin Heart EXCOR at Bambino Gesu Children's
      Hospital were included. A total of 25 patients were included in this study.
      Median age and weight at implantation were 22.4 months (range 3.6-154.2) and 10
      kg (range 4.5-36), respectively. Diagnosis included cardiomyopathy (n = 20) and
      congenital heart disease (n = 5). Eleven patients received atrial cannulation.
      Nine patients underwent biventricular assist device support. Seven patients
      underwent extracorporeal membrane oxygenation before the implantation of the
      EXCOR VAD. Median duration of VAD support was 51 days (range 2-167). Nine
      patients had evidence of acute BI including intracranial hemorrhage (n = 5) and
      cerebral ischemia (n = 4). Freedom from BI at 30, 60, and 90 days from VAD
      implantation was 80.7, 69.9, and 43.3%, respectively. Weight <10 kg at
      implantation was significantly associated with BI. BI is a frequent complication
      among children supported with EXCOR VAD and is associated with lower weight at
      implantation. However, our data do not support the association between size and
      BI. Future prospective multicenter studies are warranted to further help
      understand the etiology and the impact of BI and to improve functional outcomes
      for children undergoing EXCOR VAD mechanical support.

PMID- 23560480
TI  - Effectiveness of virtual reality using video gaming technology in elderly adults
      with diabetes mellitus.
AB  - BACKGROUND: Diabetes in elderly adults is associated with an increased risk of
      fall. The aim of study was to determine whether a virtual reality exercise (VRE)
      program would improve balance, strength, gait, and falls efficacy in elderly
      adults with diabetes. SUBJECTS AND METHODS: Fifty-five subjects with diabetes
      mellitus over 65 years of age were randomly assigned to a VRE group (VREG) (n=27)
      and a control group (CG) (n=28). The VREG received the VRE program and diabetes
      education, whereas the CG received only the diabetes education. The VRE program
      used video gaming (PlayStation((r)) 2; Sony, Tokyo, Japan) and was conducted for
      50 min twice a week for 10 weeks. Balance, muscle strength, gait, and falls
      efficacy were measured at baseline and after intervention. Measurements were
      taken using a clinical tests (the one-leg-standing test, the Berg Balance Scale,
      the functional reach test, the timed up-and-go test, and the sit-to-stand test),
      and gait analysis. A self-administered questionnaire was used to measure falls
      efficacy. RESULTS: After training, the VREG showed significantly improved
      balance, decreased sit-to-stand times, and increased gait speed, cadence, and
      falls efficacy. CONCLUSIONS: The VRE program was to maximize the effects of
      exercise by triggering players was to be fully immersed into the games and
      enhanced major influential factors on the falls of subject. This study suggests
      VRE programs are feasible and effective for reduced the risk of falls in elderly
      adults with type 2 diabetes.

PMID- 23560481
TI  - Identifying single molecular ions by resolved sideband measurements.
AB  - The masses of single molecular ions are nondestructively measured by cotrapping
      the ion of interest with a laser-cooled atomic ion, (40)Ca(+). Measurement of the
      resolved sidebands of a dipole forbidden transition on the atomic ion reveals the
      normal-mode frequencies of the two ion system. The mass of two molecular ions,
      (40)CaH(+) and (40)Ca(16)O(+), are then determined from the normal-mode
      frequencies. Isotopes of Ca(+) are used to determine the effects of stray
      electric fields on the normal mode measurement. The future use of resolved
      sideband experiments for molecular spectroscopy is also discussed. 

PMID- 23560482
TI  - Ultraviolet-induced effects on chloramine and cyanogen chloride formation from
      chlorination of amino acids.
AB  - Ultraviolet (UV)-based treatment is commonly used to augment chlorination in
      swimming pools. However, the effects of combined application of UV254/chlorine on
      disinfection byproduct (DBP) formation are incompletely defined. To examine this
      issue, experiments were conducted with amino acids (l-arginine, l-histidine, and
      glycine) that are representative of those introduced to swimming pools via human
      body fluids. For each precursor, stepwise experiments were conducted with
      chlorination and UV254 exposure, with/without post-chlorination. Net formation
      and decomposition of chloramines and cyanogen chloride (CNCl) were measured for a
      range of chlorine/precursor (Cl/P) molar ratios and UV254 doses. Substantial
      production of NH2Cl from l-arginine and l-histidine was observed at Cl/P = 1.0
      and 2.0 when post-chlorination was applied to UV254-irradiated samples. These
      results suggested a mechanism of rapid N-chlorination, followed by cleavage of
      NH3 by UV254 irradiation. CNCl formation was observed from UV254-irradiated
      samples of l-arginine and l-histidine when Cl/P = 2.0 and 3.0, as well as from
      glycine for Cl/P <= 1. Structurally related precursor compounds were examined for
      CNCl formation potential in chlorination/UV experiments. CNCl formation was
      promoted by UV254 exposure of chlorinated imidazole and guanidine compounds,
      which suggested that these groups contributed to CNCl formation. The results have
      implications with respect to the application of chlorine and UV for water
      treatment in swimming pools and other settings, such as water reuse and advanced
      oxidation processes.

PMID- 23560484
TI  - Evaluation of death pathway genes FAS and FASL polymorphisms in chronic HBV
      infection.
AB  - This study was designed to determine the possible asssociation between selected
      FAS and FASLG polymorphisms and Hepatitis B virus (HBV) infection. FAS-670 G/A,
      FAS-1377 G/A, FASLG-844 T/C and FASLG IVS2nt-124 A/G polymorphisms were genotyped
      by polymerase chain reaction and restriction fragment length polymorphism (PCR
      RFLP). A total of age and sex matched 108 controls and a hundred chronic HBV
      patients were recruited to conduct a case-control study. FAS-670 polymorphism was
      associated with chronic HBV infection (P = 0.03) FAS-1377 GG, GA and AA genotypes
      among the cases (90%, 5% and 5%, respectively) were significantly different from
      those among the controls (68%, 31.5% and 5.6%; P = 0.00). FASLG-844 allele
      distribution was similar between the groups (P = 0.17) but TC genotype (67.3%)
      was frequent in chronic HBV patients, while CC genotype was found significantly
      higher (29.6%) in controls. No association between FASLG IVS2nt-124 polymorphism
      and chronic HBV infection could be identified (P = 0.55). FAS-670 polymorphism is
      associated with chronic HBV infection, while FASLG IVS2nt-124 A/G polymorphism is
      not. The FAS-1377G/A and FASLG-844 T/C genotypes are likely to play a substantial
      role in HBV infection. Further studies evaluating polymorphisms in other genes
      related with apoptosis are needed to elucidate the role of genetic variation in
      HBV infection. 

PMID- 23560485
TI  - Roles of histone methyl-modifying enzymes in development and progression of
      cancer.
AB  - Retroviral insertional mutagenesis in mice is considered a powerful forward
      genetic strategy to identify disease genes involved in cancer. Our high
      throughput screens led to frequent identification of the genes encoding the
      enzymes engaged in histone lysine methylation. Histone methylation can positively
      or negatively impact on gene transcription, and then fulfill important roles in
      developmental control and cell-fate decisions. A tremendous amount of progress
      has accelerated the characterization of histone methylations and the enzymes that
      regulate them. Deregulation of these histone methyl-modifying enzymes has been
      increasingly recognized as a hallmark of cancer in the last few years. However,
      in most cases, we have only limited understanding for the molecular mechanisms by
      which these enzymes contribute to cancer development and progression. In this
      review, we summarize the current knowledge regarding some of the best-validated
      examples of histone lysine methyltransferases and demethylases associated with
      oncogenesis and discuss their potential mechanisms of action. 

PMID- 23560486
TI  - Organic extract contaminants from drinking water activate Nrf2-mediated
      antioxidant response in a human cell line.
AB  - Traditional risk assessment methods face challenges in estimating risks from
      drinking waters that contain low-levels of large numbers of contaminants. Here,
      we evaluate the toxicity of organic contaminant (OC) extracts from drinking water
      by examining activation of nuclear factor E2-related factor 2 (Nrf2)-mediated
      antioxidant response. In HepG2 cells, the Nrf2-mediated antioxidant response
      measured as Nrf2 protein accumulation, expression of antioxidant response element
      (ARE)-regulated genes and ARE-luciferase reporter gene assays were activated by
      OC extracts from drinking water sources that detected 25 compounds in 9
      classification groups. Individual OCs induced oxidative stress at concentrations
      much higher than their environmental levels; however, mixtures of contaminants
      induced oxidative stress response at only 8 times the environmental levels.
      Additionally, a synthetic OC mixture prepared based on the contamination
      profiling of drinking water induced ARE activity to the same extent as the real
      world mixture, reinforcing our conclusion that these mixture exposures produce
      responses relevant for human exposure situations. Our study tested the
      possibility of assessing toxicity of OCs of drinking water using a specific ARE
      pathway measurement. This approach should be broadly useful in assisting risk
      assessment of mixed environmental exposure.

PMID- 23560491
TI  - Effect of exercise performed during hemodialysis: strength versus aerobic.
AB  - RATIONAL: Patients under regular dialysis can also present alterations in the
      cardiovascular, musculoskeletal, and metabolic systems. OBJECTIVES: The aim of
      this study is to compare the effects of strength and aerobic exercises performed
      during hemodialysis (HD) in individuals with chronic renal disease. MATERIALS AND
      METHODS: Randomized clinical trial. It was developed as a program of exercises
      three times a week, in the first 2 h of HD for 8 weeks. The patients were divided
      into three groups: control (Group 1, n: 11), strength (Group 2, n: 11), and
      aerobic (Group 3, n: 10). G1 has not developed any type of physical training; G2
      utilized a training load of 40% of one repetition maximum (1RM) with anklets, and
      developed three series of 15 repetitions. G3 pedaled seated in the dialysis seat,
      during 20 min, in an ergometric bicycle, with intensity regulated by the
      perceived effort scale. Before and after 8 weeks, the following variables were
      evaluated: respiratory muscular strength, pulmonary function, functional
      capacity, blood biochemistry, and quality of life. MAIN FINDINGS: In the pre- and
      post-training comparison, there was statistically significant improvement (p <
      0.05) in the maximal inspiratory pressure (MIP), number of steps achieved (NSA),
      and quality of life (QoL) in the trained groups, as compared to the non-exercised
      group (G1). CONCLUSIONS: The strength and aerobic exercises developed during HD
      can improve the respiratory muscular strength, functional performance, and
      quality of life, when compared to individuals presenting the disease who have not
      developed any type of physical training.

PMID- 23560492
TI  - Impact of a senior fitness program on measures of physical and emotional health
      and functioning.
AB  - The SilverSneakers fitness program is a health plan benefit for Medicare
      beneficiaries that provides older adults with fitness center membership,
      customized group exercise classes, and a supportive social environment that
      promotes socialization among participants. This study evaluated the impact of the
      SilverSneakers program on physical and emotional health and activities of daily
      living (ADLs). A quasi-experimental retrospective analysis compared annual survey
      responses from SilverSneakers members (treatment N=5586) to a matched national
      random sample of Medicare Advantage organization beneficiaries (comparison
      N=22,344) in Cohort 10 of the Medicare Health Outcomes Survey. Matching was
      performed based on 6 demographic and 6 disease status variables. Survey responses
      from 2007 and 2009 were evaluated using categorical and logistic regression
      analysis. The treatment group showed significantly better physical and emotional
      health and lower impairment in both 2007 and 2009, less impairment for 4 of 6
      ADLs in 2007, and all 6 in 2009, and a higher average number of days of good
      health within the prior month for both years. Three-year longitudinal analyses
      indicated a significantly more favorable survey response trend for the treatment
      group for nearly all measures of health and ADLs. Members who exercised less
      frequently had poorer health and functioning. Overall, participation in the
      SilverSneakers program was associated with more favorable overall physical and
      social/emotional health status and fewer activity impairments, suggesting that
      the provision of senior-oriented group fitness programs may be a valuable
      approach to improve quality of life and reduce the burden associated with
      declining health and functioning as older adults age.

PMID- 23560493
TI  - Well-being and employee health-how employees' well-being scores interact with
      demographic factors to influence risk of hospitalization or an emergency room
      visit.
AB  - The goal of this study was to determine the relationship between individual well
      being and risk of a hospital event in the subsequent year. The authors
      hypothesized an inverse relationship in which low well-being predicts higher
      likelihood of hospital use. The study specifically sought to understand how well
      being segments and demographic variables interact in defining risk of a hospital
      event (inpatient admission or emergency room visit) in an employed population. A
      retrospective study design was conducted with data from 8835 employees who
      completed a Well-Being Assessment questionnaire based on the Gallup-Healthways
      Well-Being Index. Cox proportional hazards models were used to examine the impact
      of Individual Well-Being Score (IWBS) segments and member demographics on hazard
      ratios (HRs) for a hospital event during the 12 months following assessment
      completion. Significant main effects were found for the influence of IWBS
      segments, sex, education, and relationship status on HRs of a hospital event, but
      not for age. However, further analysis revealed significant interactions between
      age and IWBS segments (P=0.005) and between age and sex (P<0.0001), indicating
      that the effects for IWBS segments and sex on HRs of a hospital event are
      mediated through their relationship with age. Overall, the strong relationship
      between low well-being and higher risk of an event in employees ages 44 years and
      older is mitigated in younger age groups. These results suggest that youth
      attenuates the risk engendered in poor well-being; therefore, methods to maintain
      or improve well-being as individuals age presents a strong opportunity for
      reducing hospital events.

PMID- 23560494
TI  - Long-term outcomes of endoscopic submucosal dissection for early gastric cancer:
      a single-center retrospective study.
AB  - BACKGROUND: The aim of the present study was to examine the safety and efficacy
      of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) based on
      the long-term outcomes. PATIENTS AND METHODS: From June 2002 to March 2007, ESD
      was carried out in 472 cases and 570 lesions of EGC. Post-surgical cases and
      status-unknown cases were excluded. The following long-term outcomes were
      examined in 438 patients who were reliably followed up for at least 5 years after
      treatment (range: 5 years [60 months] to 9 years, 9 months [117 months]): local
      recurrence, metachronous recurrences, and the survival rate. RESULTS: The overall
      en bloc resection rate was 97.7% for all lesions treated by ESD. The median
      procedure time was 47.0 min (range 8-345 min). The incidence of positive
      horizontal andvertical margins was 3.7% and 3.4%, respectively. The incidence of
      perforation and postoperative bleeding was 5.3% and 4.3%, respectively. There
      were no deaths related to ESD. Local recurrence was observed in five patients
      (1.1%), and metachronous recurrences in 7.8% of the patients. The post-treatment
      5-year survival was 83.1%. There were no deaths as a result of gastric cancer
      associated with sites treated by ESD. CONCLUSION: ESD can be considered a
      standard treatment for EGC based on its expanded indications and low incidences
      of local recurrence and lymph node metastasis.

PMID- 23560495
TI  - Cell cycle regulation score predicts relapse-free survival in non-germinal centre
      diffuse large B-cell lymphoma patients treated by means of immunochemotherapy.
AB  - OBJECTIVES: The cell cycle is under strict regulation by the retinoblastoma, p53
      and p27 pathways, and the disruption of these pathways is an important
      characteristic of diffuse large B-cell lymphoma (DLBCL). In this study, we wanted
      to assess the function and prognostic significance of these pathways in DLBCL
      patients. METHODS: Tissue samples from 120 DLBCL patients treated by means of R
      CHOP-type chemotherapy were stained for the cell cycle-regulating proteins p16,
      p21, p27 and p53, and the germinal centre (GC) phenotype was determined according
      to Hans' algorithm. Based on the number of impaired cell cycle-regulating
      pathways a predictive score was obtained, covering three different prognostic
      groups: a 'favourable' group with damage in 0-1 of the studied pathways, a 'poor'
      group with damage in all three pathways and an 'intermediate' group comprising
      the rest of the patients. RESULTS: The prognosis of non-GC DLBCL patients was
      significantly poorer vs. GC phenotype patients (P = 0.015). The prognostic score
      proved especially useful among non-GC phenotype patients, with 3-yrs relapse-free
      survival of 100% vs. 62.6% vs. 24.3% in the 'favourable-', 'intermediate-' and
      'poor prognosis' groups, respectively (P = 0.003). CONCLUSION: The prognosis of
      non-GC DLBCL patients is progressively impaired with the accumulation of damage
      in different cell cycle-regulating pathways.

PMID- 23560497
TI  - Probing individual redox PEGylated gold nanoparticles by electrochemical--atomic
      force microscopy.
AB  - Electrochemical-atomic force microscopy (AFM-SECM) was used to simultaneously
      probe the physical and electrochemical properties of individual ~20 nm sized gold
      nanoparticles functionalized by redox-labeled PEG chains. The redox PEGylated
      nanoparticles were assembled onto a gold electrode surface, forming a random
      nanoarray, and interrogated in situ by a combined AFM-SECM nanoelectrode probe.
      We show that, in this so-called mediator-tethered (Mt) mode, AFM-SECM affords the
      nanometer resolution required for resolving the position of individual
      nanoparticles and measuring their size, while simultaneously electrochemically
      directly contacting the redox-PEG chains they bear. The dual measurement of the
      size and current response of single nanoparticles uniquely allows the statistical
      distribution in grafting density of PEG on the nanoparticles to be determined and
      correlated to the nanoparticle diameter. Moreover, because of its high spatial
      resolution, Mt/AFM-SECM allows "visualizing" simultaneously but independently the
      PEG corona and the gold core of individual nanoparticles. Beyond demonstrating
      the achievement of single-nanoparticle resolution using an electrochemical
      microscopy technique, the results reported here also pave the way toward using
      Mt/AFM-SECM for imaging nano-objects bearing any kind of suitably redox-labeled
      (bio)macromolecules.

PMID- 23560496
TI  - Inverse expression of hyaluronidase 2 and hyaluronan synthases 1-3 is associated
      with reduced hyaluronan content in malignant cutaneous melanoma.
AB  - BACKGROUND: Hyaluronan is an extracellular matrix glycosaminoglycan involved in
      invasion, proliferation and metastasis of various types of carcinomas. In many
      cancers, aberrant hyaluronan expression implicates disease progression and
      metastatic potential. Melanoma is an aggressive skin cancer. The role of
      hyaluronan in melanoma progression including benign nevi and lymph node
      metastases has not been investigated earlier, nor the details of its synthesis
      and degradation. METHODS: The melanocytic and dysplastic nevi, in situ melanomas,
      superficially and deeply invasive melanomas and their lymph node metastases were
      analysed immunohistochemically for the amount of hyaluronan, its cell surface
      receptor CD44, hyaluronan synthases 1-3 and hyaluronidases 1-2. RESULTS:
      Hyaluronan content of tumoral cells in deeply invasive melanomas and metastatic
      lesions was clearly reduced compared to superficial melanomas or benign lesions.
      Furthermore, hyaluronan content in the stromal cells of benign nevi was higher
      than in the premalignant or malignant tumors. The immunopositivity of
      hyaluronidase 2 was significantly increased in the premalignant and malignant
      lesions indicating its specific role in the degradation of hyaluronan during
      tumor progression. Similarly, the expression of hyaluronan synthases 1-2 and CD44
      receptor was decreased in the metastases compared to the primary melanomas.
      CONCLUSIONS: These findings suggest that the reciprocal relationship between the
      degrading and synthesizing enzymes account for the alterations in hyaluronan
      content during the growth of melanoma. These results provide new information
      about hyaluronan metabolism in benign, premalignant and malignant melanocytic
      tumors of the skin.

PMID- 23560498
TI  - A switchable surface enables visualization of single DNA hybridization events
      with atomic force microscopy.
AB  - Here we describe a novel surface that enables direct visualization of the
      hybridization of single DNA molecules with an unprecedented resolution using
      atomic force microscopy. The surface consists of single-stranded DNA probes that
      are covalently anchored to a self-assembled monolayer. The surface satisfies the
      contradictory requirements for high-resolution imaging and hybridization by
      switching the DNA-surface interaction between a strong state and a weak state.
      Our approach opens up unique opportunities in elucidating hybridization at the
      molecular scale.

PMID- 23560500
TI  - Effect of a preoperative gabapentin on postoperative analgesia in patients with
      inflammatory bowel disease following major bowel surgery: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: Postoperative pain management for patients with inflammatory bowel
      disease (IBD) can be challenging. These patients have a high tolerance to pain
      medication, and relative contraindications to the use of epidural analgesia,
      limiting the pain management options. We evaluated the effect of a single
      preoperative gabapentin dose on opioid consumption for patients with IBD
      undergoing abdominal surgery. Secondary outcomes were postoperative pain scores,
      opioid-related side effects, and patient's length of hospital stay. METHODS:
      Following Research Ethics Board approval and informed written consent, patients
      were randomly allocated into 2 groups receiving either 600 mg of oral gabapentin
      or placebo 1 hour before the surgery. A blinded anesthesiologist recorded pain
      scores at rest and movement twice daily for 2 postoperative days. Also recorded
      were opioid consumption, time of return of bowel function, time to discharge, and
      opioid-related side effects on the opioid-related symptom distress scale (ORSDS).
      RESULTS: Seventy-two patients completed the study. The difference in opioid
      consumption (P = 0.4169) and pain scores measured at rest and movement on all 4
      postoperative visits was not statistically significant. There was no significant
      difference between gabapentin and placebo on all the 11 symptoms reported on the
      ORSDS. There was a slight increase in length of hospital stay in the placebo
      group, but the return of bowel function was similar between the groups.
      CONCLUSIONS: This study examined the effect of a single preoperative
      administration of gabapentin in patients with IBD undergoing major bowel surgery.
      Our results suggest a single preoperative oral dose of gabapentin 600 mg does not
      reduce postoperative pain scores, opioid consumption, or opioid-related side
      effects.

PMID- 23560501
TI  - Psychological and adjustment problems due to acquired brain lesions in pre-school
      aged patients.
AB  - OBJECTIVE: To describe and compare psychological, behavioural and adjustment
      problems in pre-school patients with acquired brain lesions of different
      aetiology. METHODS: Three groups of patients with acquired brain lesions (14
      patients post-TBI, 18 brain tumour survivors and 23 patients with vascular or
      infectious brain lesions), ranging in age between 24-47 months, received a
      psychological evaluation, including the Child Behavior Checklist for Ages 2-3
      (CBCL) and the Vineland Adaptive Behavior Scales (VABS). RESULTS: About half of
      the total sample (47.2%) showed psychological and behavioural problems.
      Difficulties vary according to the aetiology of the brain lesions. Brain tumour
      survivors showed more marked internalizing problems, whereas children with
      vascular or infectious brain lesions scored higher on the CBCL externalizing
      scales. Children with traumatic brain injury reported intermediate scores on most
      of the CBCL scales. CONCLUSIONS: Psychological and behavioural difficulties are
      very common, not only among school-aged children and adolescents, but also among
      pre-schoolers with acquired brain lesions. The relevance and the impact of these
      difficulties must necessarily be considered when developing psychological
      treatment and rehabilitation plans and planning for social re-entry.

PMID- 23560502
TI  - Mutation of the GATA site in the erythroid cell-specific regulatory element of
      the ABO gene in a Bm subgroup individual.
AB  - BACKGROUND: The ABO blood group is important in blood transfusion. Recently, an
      erythroid cell-specific regulatory element has been identified in the first
      intron of ABO using luciferase reporter assays with K562 cells. The erythroid
      cell-specific regulatory activity of the element was dependent upon GATA-1
      binding. In addition, partial deletion of Intron 1 including the element was
      observed in genomic DNAs obtained from 111 Bm and ABm individuals, except for
      one, whereas the deletion was never found among 1005 individuals with the common
      phenotypes. STUDY DESIGN AND METHODS: In this study, further investigation was
      performed to reveal the underlying mechanism responsible for reduction of B
      antigen expression in the exceptional Bm individual. Peptide nucleic acid
      clamping polymerase chain reaction was carried out to amplify the B-related
      allele, followed by sequence determination. Electrophoretic mobility assays and
      promoter assays were performed to examine whether a nucleotide substitution
      reduced the binding of a transcription factor and induced loss of function of the
      element. RESULTS: Sequence determination revealed one point mutation of the GATA
      motif in the element. The electrophoretic mobility shift assays showed that the
      mutation abolished the binding of GATA transcription factors, and the promoter
      assays demonstrated complete loss of enhancer activity of the element.
      CONCLUSION: These observations suggest that the mutation in the GATA motif of the
      erythroid-specific regulatory element may diminish the binding of GATA
      transcription factors and down regulate transcriptional activity of the element
      on the B allele, leading to reduction of B antigen expression in erythroid
      lineage cells of the Bm individual.

PMID- 23560503
TI  - Birth trauma--risk factors and short-term neonatal outcome.
AB  - OBJECTIVE: The ability to predict birth trauma (BT) based on the currently
      recognized risk factors is limited and there is little information regarding the
      short-term neonatal outcome following BT. We aimed to identify risk factors for
      BT and to evaluate the effect of BT on short-term neonatal outcome. METHODS: A
      retrospective, cohort, case-control study of all cases of BT in a single tertiary
      center (1986-2009). The control group included the two subsequent full-term
      singleton neonates who did not experienced BT. Short-term neonatal outcome was
      compared between the groups including Apgar scores, NICU admission, duration of
      hospitalization and neurologic, respiratory and metabolic morbidity. RESULTS: Of
      the 118 280 singleton full-term newborns delivered during the study period, 2874
      were diagnosed with BT (24.3/1000). The most frequent types of BT were scalp
      injuries (63.9%, 15.5/1000) and clavicular fracture (32.1%, 7.7/1000). The
      following factors were found to be independent risk factors for BT: instrumental
      delivery (OR 7.5, 95% CI 6.3-8.9), birth weight, delivery during risk hours,
      parity, maternal age and neonatal head circumference. Cesarean delivery was the
      only factor protective of BT (OR 0.2, 95% CI 0.2-0.3). Neonates in the study
      group had a prolonged length of hospital stay (3.3 versus 2.7 d, p = 0.001), were
      more likely to be admitted to the NICU (3.9% versus 1.9%, p < 0.001), and had a
      higher rate of jaundice (11.9% versus 7.1%, p < 0.001) and neurological morbidity
      (4.7% versus 2.3%, p < 0.001). CONCLUSION: Instrumental delivery appears to be
      responsible for most cases of neonatal BT.

PMID- 23560504
TI  - 3D spectroscopy of vibrational coherences in quantum dots: theory.
AB  - In semiconductor nanocrystals, called quantum dots (QD), electronic transition
      energies, phonon frequencies, and electron-phonon coupling strengths are all
      reported to depend on the size of the crystals. The size dependencies of the
      transition energies and the mode frequencies are well characterized and
      understood. At the same time, the electron-phonon coupling dependence on size is
      controversial-even the sign of the change is not settled. In this article, third
      order response functions of a model QD resembling CdSe are calculated. The
      longitudinal optical (LO) mode is included as a relatively narrow Lorentzian
      contribution to the spectral density. A novel version of electronic 2D
      spectroscopy is investigated where a third Fourier transform is taken over a so
      called population time, leading to 3D spectral representation. The amplitude and
      phase of the 2D cuts of the 3D spectral body around the LO mode frequency are
      analyzed. The analytical power and sensitivity of the cuts in determining the
      possible Huang-Rhys factor (electron-phonon coupling strength) and the LO mode
      frequency dependence on the QD size are investigated. Peak structures in the cuts
      with a tilt relative to the diagonal are identified as sensitive signatures for
      the size dependencies. The study elucidates the 3D representation of the
      electronic 2D spectroscopy as a powerful tool for obtaining insight into
      otherwise hardly accessible characteristics of the system. 

PMID- 23560505
TI  - Cetuximab: still an option in the treatment of pancreatic cancer?
AB  - INTRODUCTION: In this review, we analyzed the current literature about cetuximab
      to clarify its role in the treatment of pancreatic cancer. Using single-agent
      gemcitabine has been the standard treatment for more than 15 years for advanced
      pancreatic cancer. The attempts at improving the results by combining it with
      several other drugs, such as fluorouracil, cisplatin, irinotecan, oxaliplatin, or
      pemetrexed produced no clear survival benefit. Recently, however, new combination
      chemotherapy regimens (e.g., FOLFIRINOX, nab-paclitaxel plus gemcitabine)
      achieved a significant survival benefit compared to gemcitabine alone. AREAS
      COVERED: Epidermal growth factor receptor (EGFR) transmembrane glycoprotein has
      been demonstrated to be overexpressed in pancreatic cancer, and it correlates
      with more advanced disease, poor survival, and the presence of metastases.
      Therefore, inhibition of the EGFR signaling pathway could be an attractive
      therapeutic target in this tumor. Although several combinations of EGFR
      inhibitors with chemotherapy demonstrate inhibition of tumor-induced
      angiogenesis, tumor cell apoptosis, and regression in xenograft models, these
      benefits remain to be confirmed. EXPERT OPINION: The encouraging results from
      preclinical and early clinical studies with cetuximab in pancreatic cancer were
      not confirmed in a Phase III trial. Cetuximab failed to demonstrate improved
      patient outcome when paired with various chemotherapeutic regimens and/or other
      biological agents.

PMID- 23560506
TI  - Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of
      randomized controlled trials.
AB  - INTRODUCTION: The use of rituximab has led to significant improvements in the
      outcome of both aggressive and indolent Non-Hodgkin's lymphoma (NHL). It is the
      first targeted therapy to be developed for the treatment of lymphoma which has
      been widely adopted. AREAS COVERED: This paper discusses the use of rituximab in
      NHL, mainly concentrating on diffuse large B cell lymphoma (DLBCL) and follicular
      lymphoma (FL), with a brief discussion about use in other types of NHL including
      mantle cell lymphoma (MCL). The use of rituximab in chronic lymphocytic leukemia
      (CLL) has been recently published in this journal by Robak (Robak T. Rituximab
      for chronic lymphocytic Leukemia. Expert Opin Biol. Ther. 2012;12(4):503-15). Non
      hematological indications for rituximab are also not discussed. A Pubmed search
      was conducted using key words of rituximab, DLBCL, FL, MCL, Burkitt's lymphoma
      and MALToma. Papers shortlisted for review included randomized control trials and
      scientific papers discussing CD20. EXPERT OPINION: In conclusion this paper has
      critically evaluated the use of rituximab in the treatment mainly of DLBCL, FL
      and MCL both at diagnosis and relapsed disease, and briefly discuses its use in
      other subtypes of lymphoma. Rituximab has significantly improved the outcome of
      patients with B cell NHL, in particular those with DLBCL and FL. Patients usually
      tolerate the treatment well, and studies have shown it to be a cost effective
      treatment.

PMID- 23560508
TI  - Cost of stroke in France.
AB  - BACKGROUND AND PURPOSE: A cost of illness study was undertaken on behalf of the
      French Ministry of Health to estimate the annual cost of stroke in France with
      the goal of better understanding the current economic burden so that improved
      strategies for care may be developed. METHODS: Using primary data from exhaustive
      national databases and both top-down and bottom-up approaches, the stroke-related
      costs for healthcare, nursing care and lost productivity were estimated. RESULTS:
      The total healthcare cost of stroke patients in France in 2007 was ?5.3 billion,
      92% of which was borne by statutory health insurance. The average cost of
      incident cases was ?16 686 per patient in the first year, while the annual cost
      of prevalent cases was a little less than half that amount (?8099). Nursing care
      costs were estimated at ?2.4 billion. Lost productivity reached ?255.9 million
      and that income loss for stroke patients was partially compensated by ?63.3
      million in social benefit payments. CONCLUSIONS: With healthcare costs
      representing 3% of total health expenditure in France, stroke constitutes an
      ongoing burden for the health system and overall economy. Nursing care added
      nearly half again the amount spent on healthcare, while productivity losses were
      more limited because nearly 80% of acute incident strokes were in patients over
      age 65. The high cost of illness underscores the need for improved prevention and
      interventions to limit the disabling effects of stroke.

PMID- 23560509
TI  - Glomus jugulare: a rare cause of facial nerve palsy.
AB  - PURPOSE: To report a case of an unusual presentation of a glomus jugulare tumour.
      DESIGN: Case report. RESULTS: Glomus jugulare is a very rare brain tumour that
      usually presents with tinnitus, hearing loss, dysphagia and hoarseness. We report
      a case where this extremely rare diagnosis presented quite differently, with
      ipsilateral proptosis and subsequent facial nerve palsy. Furthermore, the sibling
      of the presented case had also been diagnosed with the same tumour. CONCLUSIONS:
      There have only been a few case reports in the literature describing facial nerve
      palsy in the context of a glomus jugulare tumour. This case highlights that
      although paragangliomas are exceedingly rare causes of facial palsy, they should
      be included in the differential diagnosis.

PMID- 23560510
TI  - Efficient generation of functional epithelial and epidermal cells from human
      pluripotent stem cells under defined conditions.
AB  - Human pluripotent stem cells (hPSCs) have an unparalleled potential to generate
      limitless quantities of any somatic cell type. However, current methods for
      producing populations of various somatic cell types from hPSCs are generally not
      standardized and typically incorporate undefined cell culture components often
      resulting in variable differentiation efficiencies and poor reproducibility. To
      address this, we have developed a defined approach for generating epithelial
      progenitor and epidermal cells from hPSCs. In doing so, we have identified an
      optimal starting cell density to maximize yield and maintain high purity of
      K18+/p63+ simple epithelial progenitors. In addition, we have shown that the use
      of synthetic, defined substrates in lieu of Matrigel and gelatin can successfully
      facilitate efficient epithelial differentiation, maintaining a high (>75%) purity
      of K14+/p63+ keratinocyte progenitor cells and at a two to threefold higher yield
      than a previously reported undefined differentiation method. These K14+/p63+
      cells also exhibited a higher expansion potential compared to cells generated
      using an undefined differentiation protocol and were able to terminally
      differentiate and recapitulate an epidermal tissue architecture in vitro. In
      summary, we have demonstrated the production of populations of functional
      epithelial and epidermal cells from multiple hPSC lines using a new, completely
      defined differentiation strategy. 

PMID- 23560511
TI  - Zn2(VO4)(IO3): a novel polar zinc(II) vanadium(V) iodate with a large SHG
      response.
AB  - The synthesis, crystal and electronic structures, and optical properties of the
      first zinc(II) vanadium(V) iodate, namely, Zn2(VO4)(IO3), are reported.
      Zn2(VO4)(IO3) crystallizes in the noncentrosymmetric (NCS) and polar space group
      Pc (No. 7) with a = 5.2714(8) A, b = 10.0402(11) A, c = 5.5070(8) A, beta =
      101.326(10) degrees , and Z = 2. It displays a novel three-dimensional (3D)
      network structure composed of ZnO5, ZnO6, VO4, and IO3 polyhedra. One-dimensional
      (1D) chains of edge-sharing ZnO5 polyhedra and 1D chains of corner-sharing ZnO6
      octahedra along the c-axis are interconnected via corner-sharing into a two
      dimensional (2D) zinc oxide layer, and such layers are bridged by both VO4
      tetrahedra and IO3 groups into a 3D network. The polarity in the structure is
      imparted by the alignment of the stereochemically active lone pairs of the iodate
      anions along the c-axis. The second harmonics generation (SHG) measurements on
      powder samples of Zn2(VO4)(IO3) under 1064-nm laser radiation revealed a large
      response of ~6 * KDP, which is Type I phase-matchable. Thermal stability and
      optical properties, as well as theoretical calculations based on DFT methods,
      were also performed.

PMID- 23560512
TI  - Manipulation of polymer/polymer interface width from nonequilibrium deposition.
AB  - We demonstrate, using neutron reflectivity, that the width of a nonequilibrium
      interface between an organo-soluble aromatic polyimide film and triacetate
      cellulose (TAC) support film created by spin-coating or solution-casting can be
      broadened in a controllable way using a "swelling agent" in the deposition
      process. In a favorable case, the adhesion, as measured by T-peel tests, can be
      increased by a factor of 7 by adjustment of the solvent composition. The
      morphologies of the TAC fractured surfaces after peeling tests measured by AFM
      reveal that broadening of the interfacial width causes an interconnected network
      in the interface, leading to a sharp increase in the interfacial adhesion.
      Differences in the chemistry (solubility) of the materials being deposited do
      make a difference in the effectiveness of this strategy of using a "swelling
      agent". For one polyimide, a 3-fold increase in adhesion can be obtained by
      optimizing the deposition temperature, but this approach for improving adhesion
      is less effective than that of adding "swelling agent". The formation of robust
      interfaces of this type is important because of the critical roles that
      multilayer films containing polymers with special properties and tailored
      structures play in applications as diverse as computer displays, photovoltaic
      devices, and polymeric electronics. The "swelling agent" strategy makes it
      possible to produce polymer multilayer structures in a cost-effective way with
      roll-to-roll mass production using direct solution coating.

PMID- 23560513
TI  - The effects of N-acetylcysteine and ozone therapy on oxidative stress and
      inflammation in acetaminophen-induced nephrotoxicity model.
AB  - INTRODUCTION: Acetaminophen (APAP) is an analgesic and antipyretic agent. In
      overdoses, it is associated with nephrotoxicity. We examined the potential
      protective effects of N-acetylcysteine (NAC) and NAC + ozone therapy (OT)
      combination against APAP-induced nephrotoxicity. MATERIALS AND METHODS: Thirty
      two male Sprague-Dawley rats were divided into four groups: sham, control (APAP),
      NAC, and NAC + OT. In the APAP, NAC, and NAC + OT groups, kidney injury was
      induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100
      mg/kg/day). NAC + OT group received NAC (100 mg/kg/day) and ozone/oxygen mixture
      (0.7 mg/kg/day) intraperitoneally for 5 days immediately after APAP
      administration. All animals were killed at 5 days after APAP administration.
      Renal tissues and blood samples were obtained for biochemical and
      histopathological analyses. Neopterin, tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-6 and IL-10 levels were measured in sera. Malondialdehyde (MDA)
      levels and glutathione peroxidase (GPx) activities were determined in renal
      homogenates. RESULTS: NAC and NAC + OT significantly decreased MDA and TNF-alpha
      levels and increased IL-10 levels and GPx activities. Serum neopterin and IL-6
      levels were not different among all groups. APAP administration caused tubular
      necrosis in the kidney. The degrees of renal necrosis of the APAP group were
      higher than the other groups. Renal injury in rats treated with combination of
      NAC and OT were found to be significantly less than the other groups.
      CONCLUSIONS: Our results showed that NAC and OT prevented renal injury in rats
      and reduced inflammation. These findings suggest that combination of NAC and OT
      might improve renal damages because of both oxidative stress and inflammation.

PMID- 23560514
TI  - Transitional care challenges of rehospitalized veterans: listening to patients
      and providers.
AB  - Readmissions to the hospital are common and costly, often resulting from poor
      care coordination. Despite increased attention given to improving the quality and
      safety of care transitions, little is known about patient and provider
      perspectives of the transitional care needs of rehospitalized Veterans. As part
      of a larger quality improvement initiative to reduce hospital readmissions, the
      authors conducted semi-structured interviews with 25 patients and 14 of their
      interdisciplinary health care providers to better understand their perspectives
      of the transitional care needs and challenges faced by rehospitalized Veterans.
      Patients identified 3 common themes that led to rehospitalization: (1) knowledge
      gaps and deferred power; (2) difficulties navigating the health care system; and
      (3) complex psychiatric and social needs. Providers identified different themes
      that led to rehospitalization: (1) substance abuse and mental illness; (2) lack
      of social or financial support and homelessness; (3) premature discharge and poor
      communication; and (4) nonadherence with follow-up. Results underscore that
      rehospitalized Veterans have a complex overlapping profile of real and perceived
      physical, mental, and social needs. A paradigm of disempowerment and deferred
      responsibility appears to exist between patients and providers that contributes
      to ineffective care transitions, resulting in readmissions. These results
      highlight the cultural constraints on systems of care and suggest that process
      improvements should focus on increasing the sense of partnership between patients
      and providers, while simultaneously creating a culture of empowerment, ownership,
      and engagement, to achieve success in reducing hospital readmissions.

PMID- 23560515
TI  - Effects of Guided Care on providers' satisfaction with care: a three-year matched
      pair cluster-randomized trial.
AB  - It is important to understand the effects of a new care model on health
      professionals' satisfaction, which may help inform organizations' decisions
      regarding the adoption of the model. This study evaluates the effect of the
      Guided Care model of primary care on physicians', Guided Care Nurses' and
      practice staff satisfaction with processes of care for chronically ill older
      patients. In Guided Care, a specially educated registered nurse works with 2-5
      primary care physicians, performing 8 clinical activities for 50-60 chronically
      ill older patients. This model was tested in a 3-year matched-pair cluster
      randomized controlled trial with 14 pods (teams of physicians and staff) randomly
      assigned, within pairs, to provide Guided Care or usual care. Physicians and
      Guided Care Nurses were surveyed at baseline and annually for 3 years. Staff were
      surveyed at baseline and 2 years later. Physicians' satisfaction with chronic
      care processes, knowledge of patients, and care coordination were measured, as
      well as Guided Care Nurses' satisfaction with chronic care processes and staff
      perceptions of quality of care. Findings suggest that Guided Care improved
      physician satisfaction with patient/family communication and management of
      chronic care, and it may bolster staff beliefs that care is patient oriented.
      Differences in other aspects of care were not statistically significant.

PMID- 23560517
TI  - Fetal placental inflammation is associated with poor neonatal growth of preterm
      infants: a case-control study.
AB  - OBJECTIVE: To determine whether there is an association between histological
      chorioamnionitis (HCA) and postnatal growth of preterm infants in the neonatal
      period. METHOD: This case-control study is part of a larger prospective
      histological study on placentas performed in all deliveries prior to 32 weeks of
      gestation. Eligible cases involved all placentas with a diagnosis of HCA. Control
      subjects were those without HCA, matched 1:1 with case subjects according to
      gestational age (+/-1 week). Placental inflammatory status and serial weight gain
      were analyzed for all infants during the first four postnatal weeks. Based on
      placental inflammation extension, HCA was defined as maternal HCA (MHCA) or fetal
      HCA (FHCA). RESULTS: Of the 320 mother-infant pairs, 71 (22.1%) presented with
      HCA (27 MHCA and 44 FHCA). Decreases in weight gain at 21 and 28 days were
      associated with the presence of FHCA (beta coefficient +/- SE = -4.40 +/- 2.21, p
      = 0.05 and -6.92 +/- 2.96, p = 0.02, respectively), whereas no significant
      differences were found between MHCA and no-HCA groups. FHCA and MHCA were not
      identified as risk factors of weekly weight gain, after adjusting for possible
      confounders (maternal ethnicity, parity, smoking during pregnancy, infant gender,
      IUGR status, SGA status, antenatal steroids, total fluid intake, late-onset
      sepsis, BPD). CONCLUSIONS: We found an association between fetal placental
      inflammation and poor neonatal growth but we were not able to identify a specific
      week wherein weight gain could be mostly affected. Placental findings may be used
      to identify preterm infants at risk of postnatal growth failure.

PMID- 23560516
TI  - Clinical correlates of acute pulmonary events in children and adolescents with
      sickle cell disease.
AB  - OBJECTIVES: We aimed to identify risk factors for acute pulmonary events in
      children and adolescents in the Pulmonary Hypertension and the Hypoxic Response
      in SCD (PUSH) study. METHODS: Patients with hemoglobin SS (n = 376) and other
      sickle cell genotypes (n = 127) aged 3-20 yrs were studied at four centers in a
      cross-sectional manner. A subgroup (n = 293) was followed for a median of 21
      months (range 9-35). RESULTS: A patient-reported history of one or more acute
      pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in
      195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By
      logistic regression, history of acute pulmonary events was independently
      associated with patient-reported history of asthma (P < 0.0001), older age (P =
      0.001), >3 severe pain episodes in the preceding 12 months (P = 0.002), higher
      tricuspid regurgitation velocity (TRV) (P = 0.028), and higher white blood cell
      (WBC) count (P = 0.043) among hemoglobin SS patients. History of acute pulmonary
      events was associated with >3 severe pain episodes (P = 0.009) among patients
      with other genotypes. During follow-up, 43 patients (15%) had at least one new
      ACS episode including 11 without a baseline history of acute pulmonary events.
      History of acute pulmonary events (odds ratio 5.0; P < 0.0001) and younger age
      (odds ratio 0.9; P = 0.007) were independently associated with developing a new
      episode during follow-up. CONCLUSIONS: Asthma history, frequent pain, and higher
      values for TRV and WBC count were independently associated with history of acute
      pulmonary events in hemoglobin SS patients and frequent pain was associated in
      those with other genotypes. Measures to reduce pain episodes and control asthma
      may help to decrease the incidence of acute pulmonary events in SCD.

PMID- 23560518
TI  - ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant:
      implications for selection of plasma preparations for thrombotic thrombocytopenic
      purpura treatment.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is characterized by
      deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh
      frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be
      determined which is more effective. STUDY DESIGN AND METHODS: To analyze the
      interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore
      isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13
      monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were
      analyzed for their effects on high shear stress-induced platelet aggregation (H
      SIPA). RESULTS: IEF analysis of normal plasma revealed three groups of ADAMTS13
      bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9
      5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand
      disease, in which VWF is absent, whereas no bands were found in plasma of a
      patient with congenital ADAMTS13 deficiency. Mixing these plasmas generated the
      bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were
      absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose
      dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and
      the degree of inhibition at the endpoint was almost indistinguishable from those
      of the other two plasma products. CONCLUSION: Both plasma products (FFP and CSP)
      are effective for PE in TTP patients. However, CSP may be more favorable, because
      it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels
      of ADAMTS13 in complex with larger VWF multimers.

PMID- 23560519
TI  - Transcutaneous pulsed radiofrequency treatment for patients with shoulder pain
      booked for surgery: a double-blind, randomized controlled trial.
AB  - Shoulder pain is the third most common musculoskeletal problem and accounts for
      5% of general practitioner consultations. Although many treatments are described,
      there is no consensus on optimal treatment and up to 40% of patients still have
      pain 12 months after initially seeking help for pain. Previously, the effect of
      transcutaneous pulsed radiofrequency treatment (TCPRFT) was evaluated in a
      retrospective audit that showed good pain relief for a mean 395 days and
      justified this randomized sham controlled trial. In this study, 51 patients
      entered into a randomized double-blinded, placebo controlled study of TCPRFT.
      Patients were assessed at 4 and 12 weeks by a blinded observer and compared with
      baseline. We observed sustained reductions in pain at night, pain with activity,
      and functional improvement at 4 and 12 weeks with active but not sham TCPRFT. The
      25 subjects who received active treatment showed statistically significant
      reductions of 24/100 in pain at night and 20/100 of pain with activity at 4 weeks
      and 18/100 and 19/100, respectively, at 12 weeks from baseline. Statistically
      significant lower Brief Pain Inventory pain and function scores (4 and 12 weeks),
      improved pain self-efficacy (4 weeks), Oxford Shoulder scores (12 weeks), and
      internal rotation (12 weeks) were seen. Pain at both rest and shoulder elevation
      were not improved by active treatment. No complications were seen. This study of
      a simple, low risk, outpatient treatment confirms the findings of our earlier
      study of TCPRFT for knee pain and shoulder pain audit that transcutaneous pulsed
      radiofrequency treatment may help some people with painful shoulders.

PMID- 23560520
TI  - Objective Bayesian search of Gaussian directed acyclic graphical models for
      ordered variables with non-local priors.
AB  - Directed acyclic graphical (DAG) models are increasingly employed in the study of
      physical and biological systems to model direct influences between variables.
      Identifying the graph from data is a challenging endeavor, which can be more
      reasonably tackled if the variables are assumed to satisfy a given ordering; in
      this case we simply have to estimate the presence or absence of each potential
      edge. Working under this assumption, we propose an objective Bayesian method for
      searching the space of Gaussian DAG models, which provides a rich output from
      minimal input. We base our analysis on non-local parameter priors, which are
      especially suited for learning sparse graphs, because they allow a faster
      learning rate, relative to ordinary local parameter priors, when the true unknown
      sampling distribution belongs to a simple model. We implement an efficient
      stochastic search algorithm, which deals effectively with data sets having sample
      size smaller than the number of variables, and apply our method to a variety of
      simulated and real data sets. Our approach compares favorably, in terms of the
      ROC curve for edge hit rate versus false alarm rate, to current state-of-the-art
      frequentist methods relying on the assumption of ordered variables; under this
      assumption it exhibits a competitive advantage over the PC-algorithm, which can
      be considered as a frequentist benchmark for unordered variables. Importantly, we
      find that our method is still at an advantage for learning the skeleton of the
      DAG, when the ordering of the variables is only moderately mis-specified.
      Prospectively, our method could be coupled with a strategy to learn the order of
      the variables, thus dropping the known ordering assumption.

PMID- 23560522
TI  - IFAG and childhood rosacea: a possible link?
AB  - Idiopathic facial aseptic granuloma (IFAG) is a disorder that usually occurs
      during early childhood. Its pathogenesis remains poorly understood. The objective
      of this study was to investigate possible relationships between IFAG and
      childhood rosacea. This was a retrospective multicenter study of patients
      attending four French dermatologic centers diagnosed with IFAG between October
      2000 and July 2007. Patients and their parents were asked to come for a follow-up
      visit or to make an appointment for a telephone interview. Clinical symptoms of
      childhood rosacea were recorded: flushing, permanent or recurrent erythema;
      facial telangiectasia; papules and pustules on the face without comedones or
      microcysts; preferential location of the lesions on the convexity of the face;
      and ophthalmologic involvement of rosacea (recurrent chalazions, conjunctival
      hyperemia, keratitis). Thirty-eight patients, 20 girls and 18 boys, were included
      in the study. The median age at the time of diagnosis of IFAG was 43 months, with
      a median follow-up of 3.9 years. Sixteen patients (42.1%) had at least two
      criteria of childhood rosacea, 11 of 32 (34.4%) with a single lesion and 5 of 6
      (83.3%) with multiple lesions. Children with IFAG are at risk for childhood
      rosacea, and follow-up is advised, including periodic ophthalmologic assessment.

PMID- 23560523
TI  - Encapsulation of particle ensembles in graphene nanosacks as a new route to
      multifunctional materials.
AB  - Hybrid nanoparticles with multiple functions are of great interest in biomedical
      diagnostics, therapies, and theranostics but typically require complex multistep
      chemical synthesis. Here we demonstrate a general physical method to create
      multifunctional hybrid materials through aerosol-phase graphene encapsulation of
      ensembles of simple unifunctional nanoparticles. We first develop a general
      theory of the aerosol encapsulation process based on colloidal interactions
      within drying microdroplets. We demonstrate that a wide range of cargo particle
      types can be encapsulated, and that high pH is a favorable operating regime that
      promotes colloidal stability and limits nanoparticle dissolution. The cargo
      filled graphene nanosacks are then shown to be open structures that rapidly
      release soluble salt cargoes when reintroduced into water, but can be partially
      sealed by addition of a polymeric filler to achieve slow release profiles of
      interest in controlled release or theranostic applications. Finally, we
      demonstrate an example of multifunctional material by fabricating
      graphene/Au/Fe3O4 hybrids that are magnetically responsive and show excellent
      contrast enhancement as multimodal bioimaging probes in both magnetic resonance
      imaging and X-ray computed tomography in full-scale clinical instruments.

PMID- 23560524
TI  - Tolerance of base pair size and shape in postlesion DNA synthesis.
AB  - The influence of base pair size and shape on the fidelity of DNA polymerase
      mediated extension past lesion-containing mispairs was examined. Primer extension
      analysis was performed with synthetic nucleosides paired opposite the pro
      mutagenic DNA lesion O(6)-benzylguanine (O(6)-BnG). These data indicate that the
      error-prone DNA polymerase IV (Dpo4) inefficiently extended past the larger
      Peri:O(6)-BnG base pair, and in contrast, error-free extension was observed for
      the smaller BIM:O(6)-BnG base pair. Steady-state kinetic analysis revealed that
      Dpo4 catalytic efficiency was strongly influenced by the primer:template base
      pair. Compared to the C:G pair, a 1.9- and 79,000-fold reduction in Dpo4
      efficiency was observed for terminal C:O(6)-BnG and BIM:G base pairs
      respectively. These results demonstrate the impact of geometrical size and shape
      on polymerase-mediated mispair extension.

PMID- 23560525
TI  - Management of advanced non-melanoma skin cancers using helical tomotherapy.
AB  - BACKGROUND: Helical tomotherapy (HT) is a relatively new method of radiotherapy,
      the main advantages of which are an increase of irradiation dose on the target
      tumour volume and best protection of adjacent organs at risk. OBJECTIVE: To
      provide an accurate evaluation of efficiency and tolerance of HT on different
      kinds of non-melanoma skin tumours. PATIENTS AND METHODS: We analysed,
      retrospectively, 25 patients (pts) who were treated with HT for advanced non
      melanoma skin cancers. We studied the characteristics of patients and tumours,
      associated treatments, characteristics, efficacy and tolerance of HT treatment.
      RESULTS: Eight had basal cell carcinoma, Eight had cutaneous squamous cell
      carcinoma, five Merkel cell carcinoma and four adnexal carcinoma. The median age
      was 75 years (range 51-89). The median follow-up was 12 months. HT was used
      because of incomplete excision (n = 12), lymph node involvement (n = 6), non
      operable lesions (n = 4) and high risk of relapse (n = 4). The delivered dose for
      the tumour bed was between 50 and 70 Gy and for the lymph node it was between 50
      and 64 Gy. There was no grade III-IV adverse event, except one grade III
      mucositis. Fourteen pts suffered from limited toxic effects 6 months after the
      end of the treatment, mainly loss of eyebrow and teared eye. Complete remission
      was noticed for 22 pts (88%); one pt had progressive disease and two pts died.
      CONCLUSION: HT is an effective option for advanced non-melanoma skin cancers as
      radical treatment or in association with surgery. Early and late toxicity and
      cosmetic results are acceptable.

PMID- 23560526
TI  - Developments in delivery of medications for inner ear disease.
AB  - INTRODUCTION: Hearing loss, tinnitus and balance disturbance represent common
      diseases that have tremendous impact on quality of life. Despite the high
      incidence of inner ear disease in the general population, there are currently no
      dedicated pharmacologic interventions available to treat these problems. AREAS
      COVERED: This review will focus on how treatment of inner ear disease is moving
      toward local delivery at the end organ level. The authors will discuss current
      practice, ongoing clinical trials and potential areas of development such as hair
      cell regeneration and neurotrophin therapy. EXPERT OPINION: The inner ear is
      accessible through the middle ear via the oval and round windows allowing
      diffusion of drugs into the perilymph. With a better understanding of the
      physiology of the inner ear and the underlying molecular causes of inner ear
      disease there is great potential for the development of novel therapeutics that
      can be locally administered. At present, there is a rapid development of drugs to
      target diverse inner ear diseases that cause sensorineural hearing loss and
      balance dysfunction.

PMID- 23560527
TI  - Mesenchymal stem cells maintain long-term in vitro stemness during explant
      culture.
AB  - The advantage of mesenchymal stem cells (MSC) in view of cell and/or tissue
      replacement after transplantation and their prolonged clinical use raises heavy
      debates not only in the fields of tissue engineering and regenerative medicine to
      date. Explant culture of umbilical cord (UC) tissue pieces for more than 190 days
      demonstrated a similar morphology and proliferation rate of outgrowing MSC as
      compared to UC tissue cultured for 15 days. Flow cytometric analysis revealed the
      expression of the typical UC-MSC markers CD73, CD90, and CD105 with concomitant
      absence of CD14, CD31, CD34, and CD45 in all MSC populations. Moreover,
      subculture of these long-term tissue-derived MSC exhibited nearly identical
      population doublings and cell cycle distributions and demonstrated the typical
      MSC surface markers expression until passage 10 in all different explant
      cultures. Stem cell-like characteristics were also maintained throughout the long
      term MSC explant cultures, including telomerase activity and the potential to
      differentiate along the adipogenic, chondrogenic and osteogenic lineage. In
      contrast, subculture of MSC for more than 10 passages in the absence of the UC
      tissue microenvironment was uniformly associated with significantly reduced
      population doublings, cell cycle accumulation in G0/G1, increased senescence and
      a diminished expression of MCS markers indicating a progressive loss of stemness
      in all cultures. Together, these findings demonstrated that the stem cell
      characteristics of MSC can be maintained during long term in vitro culture in the
      presence of the originating tissue pieces suggesting that the corresponding
      tissue provides a microenvironment which is essential for keeping MSC in a stem
      cell-like state. 

PMID- 23560528
TI  - The association between asymptomatic coronary artery disease and CHADS2 and CHA2
      DS2 -VASc scores in patients with stroke.
AB  - BACKGROUND AND PURPOSE: CHADS2 and CHA2 DS2 -VASc scores are measurement tools
      that stratify thromboembolic risk in patients with non-valvular atrial
      fibrillation, and are predictive of cerebral atherosclerosis, fatal stroke and
      ischaemic heart disease. Patients with higher CHADS2 and CHA2 DS2 -VASc scores
      are more likely to have had an akinetic/hypokinetic left ventricular segment or a
      recent myocardial infarction, all of which are associated with coronary artery
      disease (CAD). Most of the CHADS2 score components are also risk factors for
      atherosclerosis. Thus, CHADS2 and CHA2 DS2 -VASc scores may be predictive of CAD.
      METHODS: In all, 1733 consecutive patients with acute ischaemic stroke who
      underwent multi-slice computed tomography coronary angiography were enrolled. The
      association of CHADS2 and CHA2 DS2 -VASc scores with the presence and severity of
      CAD was investigated. RESULTS: Of the 1733 patients, 1220 patients (70.4%) had
      any degree of CAD and 576 (33.3%) had significant CAD (>= 50% stenosis in at
      least one coronary artery). As the CHADS2 and CHA2 DS2 -VASc scores increased,
      the presence of CAD also increased (P < 0.001). The severity of CAD was
      correlated with CHADS2 score (Spearman coefficient 0.229, P < 0.001) and CHA2 DS2
      -VASc score (Spearman coefficient 0.261, P < 0.001). In multivariate analysis,
      after adjusting for confounding factors, CHADS2 and CHA2 DS2 -VASc scores >=2
      were independently associated with CAD. The CHA2 DS2 -VASc score was a better
      predictor of the presence of CAD than the CHADS2 score on area under the curve
      analysis. CONCLUSION: CHADS2 and CHA2 DS2 -VASc scores were predictive of the
      presence and severity of CAD in patients with stroke. When a patient has high
      CHADS2 or CHA2 DS2 -VASc scores, physicians should consider coronary artery
      evaluation.

PMID- 23560529
TI  - Source memory in normal aging and Parkinson's disease.
AB  - Several theorists have described memory in Parkinson's disease (PD) as involving
      an amplification of the deficits seen in normal aging, and drawn parallels
      between PD and frontal lesion patients. Both normal aging and frontal lobe damage
      impair memory for the context in which one has encountered information (i.e.,
      source memory). We thus sought to determine whether PD patients would show
      especially poor source memory. We assessed memory for perceptual (voice), spatial
      (location of loudspeaker), and temporal (list) source memory in 18 PD patients,
      23 healthy older adults, and 35 young people. Although both the healthy aged and
      PD groups performed more poorly than the young on most of the memory tests, the
      PD patients failed to show significantly greater impairments than the healthy
      older adults. The PD patients did perform more poorly, however, on a measure of
      executive function (the Wisconsin Card Sorting Test [WCST]). We discuss potential
      reasons why PD had a surprisingly minimal effect on source memory in our study,
      and relate our data to broader theories of memory impairment in Parkinson's
      disease. 

PMID- 23560530
TI  - Levator-Muller's muscle recession with tarsorrhaphy: a technique for corneal
      protection in cases with cicatricial upper eyelid retraction.
AB  - AIMS: Cicatricial upper eyelid retraction with exposure keratopathy and impending
      corneal perforation requires prompt intervention. Standard procedures such as
      isolated levator recession, botulinum toxin, and lid weights will only induce a
      partial ptosis. Conventional tarsorrhaphy, though ideal to achieve complete
      closure, is likely to result in dehiscence in these cases. We describe a one
      stage technique of levator and Muller's muscle recession combined with a
      tarsorrhaphy used in four patients with an impending corneal perforation due to
      cicatricial lagophthalmos. METHODS: This is an interventional, non-comparative
      retrospective case series of four patients who had undergone tarsorrhaphy in
      combination with levator recession. RESULTS: In all four cases, it was not
      possible to mechanically close the eyelids preoperatively due to cicatricial lid
      retraction involving the middle lamella. The aetiology for lagophthalmos was
      varied: (Case 1) bilateral sclerosing metastatic breast cancer involving the
      lids; (Case 2) severe anterior and middle lamella shortening due to actinic
      changes; (Case 3) middle and posterior lamella shortening due to glaucoma
      treatment and multiple surgery (Case 4) due to traumatic facial scarring and
      seventh nerve palsy. In all cases, the corneal thinning and epithelial defects
      resolved completely following surgery. In one case, we were able to partially
      reopen the tarsorrhaphy for further corneal surgery. DISCUSSION: We describe a
      safe, effective and reversible surgical procedure for managing cases with
      cicatricial upper eyelid retraction, which would otherwise lead to serious
      corneal complications.

PMID- 23560531
TI  - Xantphos-type complexes of group 9: rhodium versus iridium.
AB  - Treatment of the dimer [Rh(MU-Cl)(C8H14)2]2 (1a) with 9,9-dimethyl-4,5
      bis(diisopropylphosphino)xanthene [xant(P(i)Pr2)2] leads to the d(8) square
      planar complex RhCl{xant(P(i)Pr2)2} (2), whereas reaction of the iridium
      counterpart [Ir(MU-Cl)(C8H14)2]2 (1b) gives the d(6) octahedral compound
      IrHCl{xant(P(i)Pr2)[(i)PrPCH(Me)CH2]} (3) as a result of the intramolecular C-H
      bond activation of one of the isopropyl substituents of the phosphine. Stirring 2
      and 3 in 0.5 N KOH solutions of 2-propanol gives rise to the formation of
      hydrides RhH{xant(P(i)Pr2)2} (4) and IrH3{xant(P(i)Pr2)2} (5), respectively. In n
      octane at 60  degrees C, complex 2 is stable. However, compound 3 activates the
      alkane to give the cis-dihydride IrH2Cl{xant(P(i)Pr2)2} (6) and a mixture of 3-
      and 4-octene. Complex 6 can be also obtained by the reaction of 3 with H2. Under
      the same conditions, 2 affords the rhodium analogue RhH2Cl{xant(P(i)Pr2)2} (7).
      Compounds 2-4 react with triflic acid (HOTf) to give RhHCl(OTf){xant(P(i)Pr2)2}
      (8), IrHCl(OTf){xant(P(i)Pr2)2} (9), and RhH2(OTf){xant(P(i)Pr2)2} (10),
      respectively. The related iridium derivative IrH2(OTf){xant(P(i)Pr2)2} (11) has
      also been prepared by the reaction of 6 with Tl(OTf). Complexes 2, 6, and 9 have
      been characterized by X-ray diffraction analysis. The {xant(P(i)Pr2)2}M skeleton
      is T-shaped with the metal center situated in the common vertex.

PMID- 23560532
TI  - Mononuclear inflammatory infiltrate and microcirculation injury in acute
      rejection: role in renal allograft survival.
AB  - This study aimed at investigating associations between monocytes/macrophages (Mo)
      infiltration and three important criteria associated with acute antibody-mediated
      rejection: C4d staining, microcirculation injury, and graft survival time. By
      quantitative analysis, Mo were counted in peritubular capillaries and in the
      interstitial compartment (peritubular/interstitial Mo), and they were also
      identified in glomeruli (glomerular Mo). The study included 47 patients who
      received renal allograft between 1991 and 2009. Capillaritis and glomerulitis
      were classified by the Banff scoring system, and C4d and Mo were analyzed by
      immunohistochemistry. In the quantitative analysis, the mean values of 50 Mo per
      10 high-power fields (HPF) and 4 Mo per glomerulus were used as cut-off points
      for the peritubular/interstitial and glomerular compartments, respectively.
      Positive C4d cases were associated with the groups of biopsies with a mean value
      >=50 Mo per 10 HPF (p = 0.01) and >=4 Mo per glomerulus (p = 0.02). The group
      with a mean value >=4 Mo per glomerulus also showed association with the presence
      of glomerulitis (p = 0.02). Peritubular/interstitial Mo did not associate with
      glomerulitis. Capillaritis did not show association with peritubular/interstitial
      or glomerular Mo. As regards graft survival, the infiltration of Mo in glomeruli
      interfered with allograft survival (p = 0.01). The group with a mean value of >=4
      glomerular Mo presented worse survival at the time of the 1-year follow-up.
      According to the literature, our data showed that infiltration of mononuclear
      cells was associated with C4d staining, microcirculation injury, and
      glomerulitis, in particular, and that glomerular macrophages could influence
      renal allograft survival.

PMID- 23560533
TI  - Are antenatal steroids beneficial to severely growth restricted fetuses?
AB  - Antenatal steroids (AS) have been shown to enhance fetal maturation in preterms
      and to improve outcome. The aim of this study was to evaluate the efficacy of AS
      in premature severely intrauterine growth restricted infants. The electronic data
      of 149 inborn, single infants born 24 to 31 6/7 weeks of GA and with a BW <= 3rd
      percentile were reviewed. Infants with congenital anomalies and syndromes were
      excluded. We compared the outcome of those who received 2 doses of AS (group A,
      87 infants) with those who did not receive AS (group B, 62 infants). Sixty-eight
      infants in group A and 53 in group B were discharged home alive. AS did not
      improve the neonatal outcome, with the exception of a better cord pH and 5-min
      Apgar and we did not observe a significant difference in the Griffith's test at 2
      years of corrected age, although there was a trend to a higher incidence of
      severe global delay in the steroid group. In view of the potential cerebral and
      CVS risks associated with high circulating steroids, the indications for AS in
      such a population need to be re-evaluated.

PMID- 23560534
TI  - Inhibition of related JAK/STAT pathways with molecular targeted drugs shows
      strong synergy with ruxolitinib in chronic myeloproliferative neoplasm.
AB  - This study aimed to assess the antitumour effects, molecular mechanisms of
      action, and potential synergy of ruxolitinib with sorafenib, KNK437, dasatinib,
      and perifosine, in Philadelphia-negative chronic myeloproliferative neoplasms
      (MPN). Cytotoxic and cytostatic effects of the different compounds were
      determined in the JAK2 V617F-positive cell lines, HEL and Ba/F3 (JAK2V617F EPOR)
      , and in primary mononuclear and bone marrow CD34-positive cells from 19 MPN
      patients. Ruxolitinib [50% inhibitory concentration (IC50 )(PV)  = 15 nmol/l], as
      well as sorafenib (IC50 PV=8MUmol/l), KNK437 (IC50 PV=100MUmol/l ), and
      perifosine (IC50 PV=15MUmol/l ), were able to inhibit proliferation in cell line
      models and in primary cells from MPN patients. Dasatinib, KNK437, and sorafenib
      showed a strong synergistic effect in combination with ruxolitinib [combination
      index (CI)(PV)  < 0.3]. Western blot confirmed that ruxolitinib blocked ERK, and
      consequently STAT5 activation, sorafenib inhibited ERK, P38 and STAT5, dasatinib
      blocked SRC and STAT5, and KNK437 decreased the stability of the JAK2 protein,
      reducing its expression. Inhibiting JAK2-related proliferative pathways has the
      potential to inhibit cell proliferation in MPNs. Furthermore, the combination of
      ruxolitinib with inhibitors that target these pathways has a strong synergistic
      effect, which may be due to decreased activation of the common effector, STAT5.

PMID- 23560536
TI  - Attachment and caregiving in adult close relationships: normative processes and
      individual differences.

PMID- 23560535
TI  - Synthesis, characterization, and evaluation of pluronic-based beta-cyclodextrin
      polyrotaxanes for mobilization of accumulated cholesterol from Niemann-Pick type
      C fibroblasts.
AB  - Several lines of evidence suggest that beta-cyclodextrin (beta-CD) derivatives
      initiate the efflux of accumulated, unesterified cholesterol from the late
      endosomal/lysosomal compartment in Niemann Pick C (NPC) disease models.
      Unfortunately, repeated injections or continuous infusions of current beta-CD
      therapies are required to sustain suppression of symptoms and prolong life. In an
      effort to make CD treatment a more viable option by boosting efficacy and
      improving pharmacokinetics, a library of Pluronic surfactant-based beta-CD
      polyrotaxanes has been developed using biocompatible poly(ethylene glycol) (PEG)
      polypropylene glycol (PPG)-PEG triblock copolymers. These compounds carry
      multiple copies of beta-CD as shown by (1)H NMR, 2D nuclear Overhouser effect
      spectroscopy, gel permeation chromatography/multiangle light scattering,
      analytical ultracentrifugation analysis, matrix assisted laser
      desorption/ionization mass spectrometry, and diffusion-ordered spectroscopy.
      Analyses of free beta-cyclodextrin contamination in the compounds were made by
      reverse phase high pressure liquid chromatography and hydrophilic interaction
      liquid chromatography. Dethreading kinetics were studied by reverse phase high
      pressure liquid chromatography, UV/vis, and (1)H NMR analysis. Filipin staining
      studies using npc2(-/-) fibroblasts show significant reversal of cholesterol
      accumulation after treatment with polyrotaxane compounds. The rate and efficacy
      of reversal is similar to that achieved by equivalent amounts of monomeric beta
      CD alone. 

PMID- 23560537
TI  - Community knowledge, behaviours and attitudes about the 2009 H1N1 Influenza
      pandemic: a systematic review.
AB  - BACKGROUND: Effectiveness of pandemic plans and community compliance was
      extensively researched following the H1N1 pandemic. This systematic review
      examined community response studies to determine whether behavioural responses to
      the pandemic were related to level of knowledge about the pandemic, perceived
      severity of the pandemic and level of concern about the pandemic. METHODS:
      Literature databases were searched from March 2009 to August 2011 and included
      cross-sectional or repeated population surveys undertaken during or following the
      H1N1 pandemic which reported on community response to the pandemic. Studies using
      population subgroups and other respiratory diseases were excluded, as were
      mathematical modelling and qualitative studies. RESULTS: Nineteen unique studies
      were included. Fourteen reported pandemic knowledge, 14 reported levels of
      concern and risk perception and 18 reported pandemic behaviours. Awareness of the
      pandemic was high, and knowledge was moderate. Levels of concern and risk were
      low moderate and precautionary behavioural actions lower than intentions. The
      most commonly reported factors influencing adopting recommended behaviours were
      increased risk perception and older age, increased pandemic knowledge and being
      female. CONCLUSIONS: Important implications for future pandemic planning were
      identified. A remarkable lack of intercountry variability in responses existed;
      however, differences between populations within a single country suggest one-size
      fits-all plans may be ineffective. Secondly, differences between reported
      precautionary intentions and preventive behaviours undertaken may be related to
      people's perceived risk of infection.

PMID- 23560538
TI  - A rare association of left ventricular diverticulum and noncompaction: continuum
      of common developmental abnormality?
AB  - A previously healthy 16-year-old girl presented with history of fever of 3 months
      duration without any significant clinical finding on examination. Transthoracic
      echocardiography (TTE) revealed moderate pericardial effusion and later diagnosed
      as tubercular in etiology. Besides, TTE also showed an incidental finding of
      large left ventricular (LV) diverticulum in submitral region along the postero
      basal segment and left ventricular noncompaction (LVNC). Nonapical LV
      diverticulum is a rare variant of this uncommon congenital condition and its
      association with LVNC has not been reported in literature. Patient was discharged
      on antitubercular therapy for pericardial effusion and advised for 6 monthly
      follow-up for diverticulum. 

PMID- 23560539
TI  - Differential expression of transcription factors Snail, Slug, SIP1, and Twist in
      ameloblastoma.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) via the mechanism of
      transcription repression is a crucial process for the induction of invasiveness
      in many human tumors. Ameloblastoma is a benign odontogenic epithelial neoplasm
      with a locally infiltrative behavior. Twist, an EMT promoter, has been implicated
      in its invasiveness. The roles of the other transcription factors remain
      unclarified. MATERIALS AND METHODS: Four transcription factors, namely Snail,
      Slug, SIP1, and Twist, were examined immunohistochemically in 64 ameloblastoma
      [18 unicystic (UA), 20 solid/multicystic (SA), 4 desmoplastic (DA), and 22
      recurrent (RA)]. RESULTS: All four transcription factors were differentially
      expressed in ameloblastoma [Snail: n = 60/64 (94%); Slug: n = 21/64 (33%); SIP: n
      = 18/64 (28%); Twist: n = 26/64 (41%)] (P < 0.05). Their distribution patterns
      were heterogeneous and were not significantly different between the tumor
      invasive front and central area (P > 0.05). Intracellular protein localization
      was predominantly nuclear for Snail, cytoplasmic>nuclear for Slug and SIP1, and
      cytoplasmic/nuclear for Twist. Overexpression of Snail in most subsets (UA =
      18/18; SMA = 19/20; DA = 4/4; RA = 19/22) compared with the other transcription
      factors (P < 0.05) and selective expression for Slug, SIP1, and Twist in
      squamous/keratinous foci and at sites of epithelial cystic degeneration were
      among the main observations made. Stromal cells surrounding immunoreactive tumor
      cells tended to stain positive. CONCLUSIONS: Present findings suggest that these
      transcription factors probably play differential roles in mediating local
      invasiveness in ameloblastoma. Overexpression of Snail in most subsets suggests
      that this molecule is most likely the prototype transcription factor involved in
      inducing EMT in the ameloblastoma.

PMID- 23560540
TI  - A multi-class, multi-analyte method for routine analysis of 84 veterinary drugs
      in chicken muscle using simple extraction and LC-MS/MS.
AB  - A multi-residue method for the simultaneous determination of 84 veterinary drug
      residues (benzimidazoles, quinolones, nitromidazoles, beta-lactams, macrolides,
      triphenylmethane dyes, sulphonamides and tetracyclines) in chicken muscle tissue
      has been developed. Sample preparation is a simple one-step procedure based on
      liquid extraction with ethylenediamine tetraacetic acid-succinate buffer and
      acetonitrile, followed by phase separation and evaporation of the supernatant.
      The extract was diluted with 0.1% formic acid and analysed by using LC-MS/MS. The
      method has been validated in chicken muscle below the individual MRLs for each
      analyte. Recoveries of analysed drugs at fortified levels (2.5-80 ng g(-1)) were
      between 60% and 100% for most compounds, corrected for signal suppression and
      enhancement. Acceptable results regarding linearity of the method, precisions and
      LOQs were achieved for 84 of 91 investigated substances. The trueness was in the
      range of +/-10%. The LOD ranged from 0.7 to 20 ng g(-1), and the LOQ ranged from
      2.0 to 48 ng g(-1) (signal/noise 10-30) for all analytes and was below the
      established MRL of each compound. 

PMID- 23560542
TI  - Modeling the conformational preference of the carbon-bonded covalent adduct
      formed upon exposure of 2'-deoxyguanosine to ochratoxin A.
AB  - The conformational flexibility of the C8-linked guanine adduct formed from
      attachment of ochratoxin A (OTA) was analyzed using a systematic computational
      approach and models ranging from the nucleobase to the adducted DNA helix. A
      focus was placed on the influence of the C8-modification of 2'-deoxyguanosine
      (dG) on the preferred relative arrangement of the nucleobase and the C8
      substituent and, more importantly, the anti/syn conformational preference with
      respect to the glycosidic bond. Although OTA is twisted with respect to the base
      in the nucleobase model, addition of the deoxyribose sugar induces a further
      twist and restricts rotation about the C-C linkage due to close contacts between
      OTA and the sugar. The nucleoside model preferentially adpots a syn orientation
      (by 10-20 kJ mol(-1) depending on the OTA conformation) due to the presence of an
      O5'-H...N3 interaction. However, when this hydrogen bond is eliminated, which
      better mimics the DNA environment, a small (<5 kJ mol(-1)) anti/syn energy
      difference is predicted. Inclusion of the 5'-monophosphate group leads to an up
      to 20 kJ mol(-1) preference for the syn (nucleotide) conformation due to
      stabilizing base-phosphate interactions involving the amino group of guanine.
      Nevertheless, MD simulations and free energy analysis predict that both syn- and
      anti-conformations of OTB-dG are equally stable in helices when paired opposite
      cytosine. These results indicate that the adduct will likely adopt a syn
      conformation in an isolated nucleoside and nucleotide, while a mixture of syn and
      anti conformations will be observed in DNA duplexes. Since the syn conformation
      could stabilize base mismatches upon DNA replication or Z-DNA structures with
      varied biological outcomes, future computational and experimental work should
      elucidate the consequences of the conformational preference of this potentially
      harmful DNA lesion.

PMID- 23560541
TI  - Resting heart rate: its correlations and potential for screening metabolic
      dysfunctions in adolescents.
AB  - BACKGROUND: In pediatric populations, the use of resting heart rate as a health
      index remains unclear, mainly in epidemiological settings. The aims of this study
      were to analyze the impact of resting heart rate on screening dyslipidemia and
      high blood glucose and also to identify its significance in pediatric
      populations. METHODS: The sample was composed of 971 randomly selected
      adolescents aged 11 to 17 years (410 boys and 561 girls). Resting heart rate was
      measured with oscillometric devices using two types of cuffs according to the arm
      circumference. Biochemical parameters triglycerides, total cholesterol, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol and glucose
      were measured. Body fatness, sleep, smoking, alcohol consumption and
      cardiorespiratory fitness were analyzed. RESULTS: Resting heart rate was
      positively related to higher sleep quality (beta = 0.005, p = 0.039) and
      negatively related to cardiorespiratory fitness (beta = -0.207, p = 0.001). The
      receiver operating characteristic curve indicated significant potential for
      resting heart rate in the screening of adolescents at increased values of fasting
      glucose (area under curve = 0.611 +/- 0.039 [0.534 - 0.688]) and triglycerides
      (area under curve = 0.618 +/- 0.044 [0.531 - 0.705]). CONCLUSION: High resting
      heart rate constitutes a significant and independent risk related to dyslipidemia
      and high blood glucose in pediatric populations. Sleep and cardiorespiratory
      fitness are two important determinants of the resting heart rate.

PMID- 23560543
TI  - Total synthesis of daptomycin by cyclization via a chemoselective serine
      ligation.
AB  - A total synthesis of daptomycin, the first natural product antibiotic launched in
      a generation, was achieved. This convergent synthesis relies on an efficient
      macrocyclization via a serine ligation to assemble the 31-membered cyclic
      depsipeptide. The difficult esterification by the nonproteinogenic amino acid
      kynurenine was accomplished via the esterification of a threonine residue by a
      suitably protected Trp ester, followed by ozonolysis. This synthesis provides a
      foundation and framework to prepare varied analogues of daptomycin to establish
      its structure-activity profile.

PMID- 23560544
TI  - The summary of FUT1 and FUT2 genotyping analysis in Chinese para-Bombay
      individuals including additional nine probands from Guangzhou in China.
AB  - BACKGROUND: The para-Bombay phenotype is characterized by the absence or weak
      expression of ABH antigens on the surface of red blood cells, but normal
      expression in saliva. STUDY DESIGN AND METHODS: The para-Bombay phenotype of the
      nine Chinese probands was identified by standard serologic techniques. The coding
      regions of FUT1 and FUT2 genes were amplified by polymerase chain reaction and
      then directly sequenced. ABO genotyping was performed by polymerase chain
      reaction with sequence-specific priming method. The FUT1 and FUT2 genotypes and
      the distribution in all reported Chinese para-Bombay individuals including our
      study were also summarized. RESULTS: Five FUT1 genotypes, h1h3 (n = 3), h1h2 (n =
      3), h1h1 (n = 1), h3h3 (n = 1), and h2h3 (n = 1), and three functional FUT2
      genotypes, Se(357) Se(357) (n = 4), Se(357) Se(357, 716) (n = 4), and Se(357)
      Se(357, 385) (n = 1) described before were identified in nine probands.
      CONCLUSIONS: The review of the literature shows that a total of 17 FUT1 alleles
      and four FUT2 alleles (Se(357), Se(357,716), Se(357 385), Se) have been
      identified in Chinese para-Bombay individuals. The four FUT1 alleles, h1
      (547delAG), h2 (880delTT), h3 (C658T), and h4 (C35T; A980C) are most prevalent,
      which account for more than 90% of all allele counts and are essential to be
      involved when developing para-Bombay genotyping kit for Chinese.

PMID- 23560545
TI  - Quality of health care of atopic eczema in Germany: results of the national
      health care study AtopicHealth.
AB  - BACKGROUND: The successful treatment of atopic eczema (AE) should result in the
      improvement of both physical symptoms and patient's quality of life (QoL). This
      study was conducted using a sample of dermatologists throughout Germany. This is
      due to dermatologists being the main health care providers of AE. OBJECTIVES:
      Obtaining reliable data on quality of care of AE from both the patient's and the
      physician's perspective. METHODS: This cross-sectional study assessed: the
      individual clinical history; dermatology-specific QoL (DLQI); state of health (EQ
      5d-VAS); treatments; burden caused by disease and treatment; patient-defined
      treatment benefit (PBI). RESULTS: Data from 1678 adult patients (60.5% female,
      mean age: 38.4 +/- 15.9) were analysed. The most frequently used treatments
      during the last five years were emollients (90.4%) and topical corticosteroids
      (85.5%). In this study, 75.8% of the patients felt only moderately or not at all
      impaired by their treatment. The mean DLQI (0 = minimum-30 = maximum QoL
      impairment) was 8.5 +/- 6.5. The EQ-5d-VAS (100 = best possible) was 63.6 +/-
      22.0 on average. 26.6% reported suffering 'often' or 'every night' from
      sleeplessness due to severe itching. Mean PBI was 2.4 +/- 1.1 (4 = maximum
      benefit). CONCLUSIONS: This study provides first data on the health care of
      adults with AE in Germany at a national level and reveals the need for a more
      effective care. Whereas most patients consider their treatment-related burden as
      low, the daily burden of the disease seems to be high: one third reports
      sleeplessness due to itching which indicates insufficient therapeutic regimes in
      these cases. A better implementation of the German national guideline for AE and
      a systematic analysis of the difficulties causing its limited effects is needed.

PMID- 23560546
TI  - Cardiovascular toxicity of tyrosine kinase inhibitors.
AB  - INTRODUCTION: Small-molecule tyrosine kinase inhibitors (TKIs) have
      revolutionized the management of many malignancies. However, they also have been
      shown to be associated with a certain degree of cardiovascular side effects that
      are often reversible. AREAS COVERED: As the number of new TKIs continues to grow,
      it is expected that clinicians will be facing the challenge of early detection
      and 10 management of these side effects while balancing the risk-benefit ratios
      of continuing with life-saving cancer therapy medications. This review will
      present the current knowledge related to incidence and proposed mechanisms of
      cardiovascular side effects of TKIs and also discuss treatment recommendations
      when available EXPERT OPINION: We will present and discuss available data and
      suggest recommendations related to patient monitoring and early identification of
      TKIs related cardiovascular toxities.

PMID- 23560547
TI  - Subcostal transversus abdominis plane phenol injection for abdominal wall cancer
      pain.
AB  - A subcostal transversus abdominis plane (TAP) phenol injection was performed on a
      patient with refractory cancer pain due a metastatic involvement of the abdominal
      wall. A diagnostic block with local anesthetic was performed under ultrasound
      guidance (USG), resulting in a decrease of 80% and 100% in dynamic and static
      visual analog scale (VAS) for pain, respectively, for 20 hours. A phenol
      injection was then performed under USG. The patient reported 70% and 100%
      reduction in the dynamic and static VAS for pain and had a 50% decrease in the
      opioid requirement that was maintained for 2 months. TAP blocks offer an
      interesting tool for either diagnosis or therapeutic purpose in chronic pain
      management. USG provides an optimal approach to soft-tissue lesions where
      fluoroscopy techniques are not useful.

PMID- 23560548
TI  - Sr7Co4(CO3)O(13-delta) (delta = 1.64), an original cobaltite derivative of the
      Ruddlesden-Popper series.
AB  - The oxycarbonate Sr7Co4(CO3)O11.36 exhibits a peculiar structure that has been
      characterized by combining transmission electron microscopy analyses and neutron
      diffraction. It consists of a regular intergrowth between the m = 2 and
      carbonated m = 3 members of the Sr(m+1)Co(m)O3(m+1) Ruddlesden-Popper (RP)
      series, Sr3Co2O5.87 and Sr4Co2(CO3)O5.49, respectively. A description of the
      structure is proposed to provide identification of the different building blocks.
      This material is semiconducting and presents a complex magnetic behavior,
      characteristic of what is observed for the RP(2) or RP(3) series, with a cobalt
      valency close to 2.7.

PMID- 23560549
TI  - Screening tools for fitness to drive after traumatic brain injury and stroke.

PMID- 23560550
TI  - Orbital myxoma: a case report.
AB  - Orbital myxomas are extremely rare tumors. We describe a 75-year old male patient
      with lower eyelid ectropion and 8-mm of left non-axial proptosis. Orbital CT and
      MRI revealed a well-demarcated lesion in the lateral quadrant of the orbit. After
      complete surgical excision, histopathological examination led to the diagnosis of
      orbital myxoma. The patient was followed-up for 1 year without recurrence.

PMID- 23560551
TI  - Obstetric anal sphincter injury, risk factors and method of delivery - an 8-year
      analysis across two tertiary referral centers.
AB  - OBJECTIVE: Obstetric anal sphincter injury (OASIS) represents a major cause of
      maternal morbidity and is a risk factor for the development of fecal
      incontinence. We set out to analyze the incidence of OASIS and its association
      with mode of delivery in two large obstetric hospitals across an 8-year study
      period. METHODS: This was a prospective observational study carried out at two
      large tertiary referral centers serving a single urban population, from 2003 to
      2010. Incidence of OASIS was examined as well as the influence of parity and mode
      of delivery on the occurrence of OASIS. RESULTS: During the study period, there
      were 100 307 vaginal deliveries at the two hospitals. There was a total of 2121
      cases of OASIS from 2003 to 2010, giving an incidence of 2.1% of vaginal
      deliveries. Patients were more likely to suffer an OASIS when having a forceps
      delivery than when having a normal vaginal delivery (8.6% versus 1.3%, p <
      0.0001, OR: 7.1, CI: 6.4-7.9). Vacuum delivery also carried an increased risk of
      sphincter injury compared with normal delivery (3.7% versus 1.3%, p < 0.0001, OR:
      2.9, CI: 2-2.6). About 16.7% of infants delivered were macrosomic (birthweight >
      4 kg). The rate of episiotomy during the study was 19.1%. CONCLUSION: These
      results demonstrate that OASIS remains an important cause of maternal morbidity
      in contemporary obstetric practice. These results will likely be of value in risk
      management planning and patient debriefing in what is a highly litigious area of
      obstetrics.

PMID- 23560552
TI  - Nanoconfinement induced formation of core/shell structured mesoporous carbon
      spheres coated with solid carbon shell.
AB  - A novel method for the fabrication of core/shell structured mesoporous carbon
      spheres with solid shell using a template method has been presented. The unique
      molecular nanostructures are characterized by XRD, TEM, TGA, and nitrogen
      adsorption/desorption measurement. The formation mechanism of the mesostructured
      carbon spheres with a carbon shell is proposed according to the experimental
      results. Nanoconfinement effect, occurring in the core/shell structured template,
      is believed to play a key role in mediating the formation of these hierarchical
      carbon mesostructures, with SnO2 as a template and C2H4 as a carbon source of a
      mesoporous carbon core. This synthesis method is simple, straightforward, and
      suitable for the preparation of various nanostructures that are unique scaffolds
      in catalytic and electrochemical applications.

PMID- 23560553
TI  - Multiple myeloma Leu167Ile (c.499C>A) mutation prevents XBP1 mRNA splicing.

PMID- 23560554
TI  - The introduction of the national e-health record into Australian community
      pharmacy practice: pharmacists' perceptions.
AB  - OBJECTIVE: Personally Controlled Electronic Health Records (PCEHRs) were
      introduced for Australian health consumers in July 2012. This study aimed to
      determine, in the months prior to the launch, community pharmacists' perceptions
      about practical and professional aspects relating to integration of the PCEHR
      into pharmacy practice, with a view to informing practice guidelines and
      training. METHODS: Semi-structured interviews with 25 pharmacy owners and/or
      managers from 24 community pharmacies in Perth, Western Australia, were
      undertaken during March-April 2012. Participants were given a standardised
      briefing about the PCEHR before exploratory questioning regarding the expected
      integration, benefits and challenges of the system in pharmacy practice. KEY
      FINDINGS: Despite some awareness of the impending introduction of PCEHRs via the
      lay media, pharmacists were almost unanimously uninformed about the intended
      rollout, design and functionality of the system for health consumers and
      practitioners. Participants expressed concerns regarding patients' control over
      their data management, time associated with staff training, technical upgrades
      and resource allocation. Obstacles included pharmacists' inability to
      legitimately access patient data outside consultations. Pharmacists expected
      flexibility to record clinical activities and health services. Priorities
      identified for the profession were remuneration, medico-legal guidelines and
      boundaries, and clarification of roles and responsibilities. CONCLUSIONS: Despite
      being unaware of details surrounding integration of PCEHRs in practice, community
      pharmacists provided insights into their expectations and concerns and the
      perceived benefits relating to implementation of the system. Training priorities
      and practice guidelines should address ethical data management and optimal use of
      electronic health records for clinical services.

PMID- 23560555
TI  - Prospective assessment of the gastroesophageal microbiome in VLBW neonates.
AB  - BACKGROUND: The distal GI microbiota of hospitalized preterm neonates has been
      established to be unique from that of healthy full-term infants; the proximal GI,
      more specifically gastroesophageal colonization has not been systematically
      addressed. We prospectively evaluated early colonization of gastroesophageal
      portion of the GI tract of VLBW infants. METHODS: This study involved 12 infants
      admitted to a level III NICU with gestational age (GA) 27 +/- 0.5 weeks and birth
      weight 1105 +/- 77 grams. The gastroesophageal microbial flora was evaluated
      using 16S rDNA analysis of aspirates collected in a sterile manner during the
      first 28 days of life. RESULTS: Bacteria were detected in 9 of the 12 neonates.
      Ureaplasma was the dominant species in the first week of life, however,
      staphylococci were the predominant bacteria overall. By the fourth week, Gram (-)
      bacteria increased in abundance to account for 50% of the total organisms.
      Firmicutes were present in the majority of the neonates and persisted throughout
      the 4 weeks comprising nearly half of the sequenced clones. Noticeably, only two
      distinct species of Staphylococcus epidermidis were found, suggesting acquisition
      from the environment. CONCLUSIONS: In our neonates, the esophagus and stomach
      environment changed from being relatively sterile at birth to becoming colonized
      by a phylogenetically diverse microbiota of low individual complexity. By the
      fourth week, we found predominance of Firmicutes and Proteobacteria. Bacteria
      from both phyla (CONS and Gram (-) organisms) are strongly implicated as causes
      of hospital-acquired infections (HAI). Evaluation of the measures preventing
      colonization with potentially pathogenic and pathogenic microorganisms from the
      hospital environment may be warranted and may suggest novel approaches to
      improving quality in neonatal care.

PMID- 23560556
TI  - Distinct structural and redox properties of the heme active site in bacterial dye
      decolorizing peroxidase-type peroxidases from two subfamilies: resonance Raman
      and electrochemical study.
AB  - Spectroscopic data of dye decolorizing peroxidases (DyPs) from Bacillus subtilis
      (BsDyP), an A subfamily member, and Pseudomonas putida (PpDyP), a B subfamily
      enzyme, reveal distinct heme coordination patterns of the respective active
      sites. In solution, both enzymes show a heterogeneous spin population, with the
      six-coordinated low-spin state being the most populated in the former and the
      five-coordinated quantum mechanically mixed-spin state in the latter. We ascribe
      the poor catalytic activity of BsDyP to the presence of a catalytically
      incompetent six-coordinated low-spin population. The spin populations of the two
      DyPs are sensitively dependent on the pH, temperature, and physical, i.e.,
      solution versus crystal versus immobilized, state of the enzymes. We observe a
      redox potential for the Fe(2+)/Fe(3+) couple in BsDyP (-40 mV) at pH 7.6
      substantially more positive than those reported for the majority of other
      peroxidases, including PpDyP (-260 mV). Furthermore, we evaluate the potential of
      the studied enzymes for biotechnological applications on the basis of
      electrochemical and spectroelectrochemical data.

PMID- 23560557
TI  - Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review
      of the literature.
AB  - BACKGROUND: Takotsubo or stress-induced cardiomyopathy is a form of reversible
      cardiomyopathy commonly associated with emotional or physical stress.
      Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy,
      with only 12 cases reported in the literature. Here, we report a case of thyroid
      storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease.
      PATIENT FINDINGS: A 71-year-old woman presented with abdominal pain, vomiting,
      confusion, and history of weight loss. She was initially diagnosed and treated
      for diabetic ketoacidosis at another hospital and was transferred to our hospital
      one day after initial presentation because of concern for acute coronary
      syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of
      cardiac catheterization. At that time, she was diagnosed and treated for thyroid
      storm. Follow-up 7 weeks later revealed improvement of her cardiac function and
      near-normalization of thyroid hormone levels. SUMMARY: In this patient, who
      presented with symptoms of heart failure, acute coronary syndrome was initially
      considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid
      storm was ultimately made based on cardiac catheterization and laboratory
      investigation. CONCLUSIONS: Thyrotoxicosis is associated with adverse
      disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a
      presenting manifestation of thyroid storm, perhaps related to excess
      catecholamine levels or sensitivity.

PMID- 23560558
TI  - Transplantation of bone marrow mononuclear cells reduces mortality and improves
      renal function on mercury-induced kidney injury in mice.
AB  - OBJECTIVE: Recent studies have demonstrated the therapeutic effects of bone
      marrow-derived cells in tissue regeneration. The aim of this study was to
      investigate the effects of bone marrow mononuclear cell (BMMC) transplantation in
      a mouse model of acute renal failure (ARF) induced by mercuric chloride. METHODS:
      BMMC was isolated from male BALB/c mice and injected into female mice treated
      with a lethal dose (LD90) of mercuric chloride. Survival rate, histopathological
      analysis, and assessment of urea, creatinine, sodium, potassium, and mercury
      levels were carried out. RESULTS: Cellular therapy with BMMC significantly
      reduced the mortality induced by mercuric chloride (p < 0.05). This finding
      correlated with a decrease in serum levels of urea (p = 0.04) and potassium (p <
      0.01). However, no differences in renal morphology were observed when BMMC
      treated and control group were compared. CONCLUSION: Transplanted BMMC improve
      renal function and reduce mortality and, therefore, may represent a new
      therapeutic alternative to treat ARF.

PMID- 23560559
TI  - A perfluoroaryl-cysteine S(N)Ar chemistry approach to unprotected peptide
      stapling.
AB  - We report the discovery of a facile transformation between perfluoroaromatic
      molecules and a cysteine thiolate, which is arylated at room temperature. This
      new approach enabled us to selectively modify cysteine residues in unprotected
      peptides, providing access to variants containing rigid perfluoroaromatic
      staples. This stapling modification performed on a peptide sequence designed to
      bind the C-terminal domain of an HIV-1 capsid assembly polyprotein (C-CA) showed
      enhancement in binding, cell permeability, and proteolytic stability properties,
      as compared to the unstapled analog. Importantly, chemical stability of the
      formed staples allowed us to use this motif in the native chemical ligation
      mediated synthesis of a small protein affibody that is capable of binding the
      human epidermal growth factor 2 receptor.

PMID- 23560560
TI  - Highly selective recognition and fluorescence imaging of adenosine polyphosphates
      in aqueous solution.
AB  - The design and synthesis of chemosensors for the recognition of a certain
      nucleoside polyphosphate among various structurally similar nucleoside
      polyphosphates remain a fundamental challenge. Herein, we report the new
      fluorescent chemosensor [Zn2L](ClO4)4 (1; L = (3,6,10,13,17,20,24,27-octaaza
      1,15(2,6)-dipyridina-8,22(9,10)-dianthracenacyclooctacosaphane), which can
      selectively recognize adenosine polyphosphates (ATP and ADP) among various
      nucleoside polyphosphates, with a large fluorescence enhancement (Fmax/F0 = 70
      and 80 for ATP and ADP, respectively) and strong binding affinity (K = 3.1 *
      10(11) M(-1) for [Zn2HL(H-1ATP)2](-), 2.8 * 10(11) M(-1) for [Zn2L(H-1ATP)2](2-),
      and 1.5 * 10(13) M(-1) for [Zn2L(H-1ADP)2](2-)) in aqueous solution at
      physiological pH 7.40. The structure of [Zn2L](P2O7) (2) was investigated, which
      shows that MU2-pyrophosphate anions alternately link [Zn2L](4+) cations to
      generate a 1D coordination polymer. The results of (31)P NMR studies and DFT
      calculations reveal that the two Zn(II) ions in 1 can interact with ATP/ADP
      anions through coordination interactions between Zn(II) and the polyphosphate
      groups, and two anthracene moieties in 1 can interact with adenine groups from
      two ATP or ADP anions through stacking interactions to form a sandwichlike
      structure. These multiple recognition interactions between 1 and ATP/ADP enhance
      the affinity and selectivity of 1 toward ATP/ADP. Due to its highly selective and
      sensitive ability to detect adenosine polyphosphates, 1 was successfully applied
      to fluorescence imaging for ATP and ADP in living cells, demonstrating the
      potential utility of 1 as a fluorescent chemosensor for detecting ATP and ADP.

PMID- 23560561
TI  - Drug safety evaluation of desogestrel.
AB  - INTRODUCTION: Desogestrel (DSG) is a third-generation progestin. It is commonly
      used in various formulations for hormonal contraception including combinations
      with ethinyl estradiol (EE), progestin-only pill and subdermal implants. DSG is
      also used in menopausal patients for hormone replacement therapy (HRT). AREAS
      COVERED: The current manuscript aims to review the available data on safety and
      tolerability of DSG in oral contraception and HRT. The material included in the
      manuscript was searched and obtained via Medline, PubMed and EMBASE up to
      September 2012 using the search terms 'adverse events, side effects,
      tolerability' in combination with 'desogestrel and progestins'. EXPERT OPINION:
      DSG is frequently used as contraceptive and it shows good contraceptive efficacy
      as demonstrated by the Pearl indexes reported in the studies reviewed in this
      manuscript. It is a versatile compound; in fact, it can be used either as
      progestin-only contraceptive or in combination with EE, and different
      formulations are available (such as the subdermal implant). In contraception, DSG
      is generally well tolerated but its use is associated with doubled risk of venous
      thromboembolism compared to second-generation progestins. Although DSG is
      efficacious in HRT, it may not represent the best choice due to the potential
      higher risk of breast cancer compared with progesterone or dydrogesterone.

PMID- 23560562
TI  - Data and interpretation: economic evaluations in transfusion medicine, Part 4.

PMID- 23560563
TI  - Physical occupational exposures during working life and quality of life after
      labour market exit: results from the GAZEL study.
AB  - OBJECTIVE: To investigate variations in quality of life at older ages, we take a
      life course perspective to analyse long-term effects of physical working
      conditions upon quality of life after retirement. In doing so, we study to what
      extent these associations are explained by individuals' health at older ages.
      METHOD: We use administrative data and self-administered questionnaire responses
      from the French GAZEL cohort. Quality of life was assessed with CASP-19 in 2009
      and related to three types of physical working conditions during previous working
      life: (1) ergonomic strain, (2) physical danger and (3) exposures to chemicals.
      Health was assessed in 2007 with the SF-36 Health Survey. Multiple regressions
      were calculated in retired men only, controlling for important confounders
      including social position. RESULTS: In contrast to men, few women were exposed to
      strenuous and dangerous working conditions in this cohort and were not included
      in subsequent analyses. Negative effects on retired men's quality of life were
      found for the physical occupational exposures of ergonomic strain and physical
      danger, but not for chemical exposures. Effects were attenuated after the
      introduction of physical and mental health to the models, indicating an indirect
      effect of physical working conditions upon quality of life via health.
      CONCLUSION: Adverse physical working conditions have long-term consequences for
      health and quality of life at older ages. Improvements to physical working
      conditions may improve individuals' quality of life over the long term.

PMID- 23560564
TI  - Chronic radiation enteritis and malnutrition.
AB  - Radiation enteritis is defined as the loss of absorptive capacity of the
      intestine following irradiation, which is most commonly seen after radiotherapy
      for pelvic and abdominal malignancies. It is divided into acute and chronic forms
      and usually presents with diarrhea and malabsorption. Malnutrition is a common
      complication of chronic radiation enteritis (CRE). We reviewed the etiology,
      prevalence, symptoms, diagnosis and management of CRE and CRE with malnutrition
      in this article. Functional short bowel syndrome as a cause of malnutrition in
      CRE is also considered. The diagnostic work-up includes serum markers, endoscopy,
      cross-sectional imaging and the exclusion of alternative diagnoses such as
      recurrent malignancy. Management options of CRE include dietary manipulation,
      anti-motility agents, electrolyte correction, probiotics, parenteral nutrition,
      surgical resection and small bowel transplantation. Treatment may also be
      required for coexisting conditions including vitamin B12 deficiency, bile acid
      malabsorption and depression.

PMID- 23560565
TI  - The value of beta-blockers administration during recovery phase of dobutamine
      stress echocardiography: a review.
AB  - Dobutamine stress echocardiography (DSE) is a successful technique for detection
      of ischemia in patients with suspected coronary artery disease (CAD). There are
      some data that administration of beta-blocker after peak infusion of dobutamine
      can improve sensitivity. The goal of this manuscript is to review the current
      literature in regard to the mechanism and accuracy of post-dobutamine beta
      blocker administration for ischemia detection. In this review, we present 2 case
      reports followed by detailed review of the literature. 

PMID- 23560566
TI  - Can security-enhancing interventions overcome psychological barriers to
      responsiveness in couple relationships?
AB  - Recent studies have shown that both dispositional and experimentally enhanced
      attachment security facilitate compassion and altruism. Here we report findings
      from a laboratory experiment, replicated in two countries (Israel and the United
      States), testing the hypotheses that (a) increased security (accomplished through
      subliminal priming) fosters caregiving behavior toward a romantic partner who
      discloses a personal problem, and (b) this increased security overcomes barriers
      to responsiveness induced by mental depletion. We gathered data on participants'
      attachment insecurities, randomly assigned them to one of four mental depletion
      (yes, no) and priming (security, neutral) conditions, and coded their behavior in
      an interaction with their romantic partner who was disclosing a personal problem.
      Dispositional attachment insecurities and manipulated mental depletion adversely
      affected caregiving, but security priming overrode the detrimental effects of
      both mental depletion and attachment insecurity in both Israel and the United
      States.

PMID- 23560567
TI  - The prevalence and risk factors of adolescent acne among schoolchildren in
      Lithuania: a cross-sectional study.
AB  - BACKGROUND: Acne is one of the most common chronic inflammatory dermatological
      diseases among adolescents. OBJECTIVES: We sought to estimate the prevalence of
      acne among schoolchildren and its association with puberty, body mass index
      (BMI), acne history of parents, nutritional habits, smoking and alcohol
      consumption. METHODS: A cross-sectional study was conducted on 1277 pupils aged 7
      19 years. Children were interviewed with self-administered questionnaires, and
      were subsequently examined by one specially trained dermatologist. To evaluate
      the onset of puberty, girls provided details about their menarche and boys--about
      their facial hair growth. RESULTS: The overall response rate of the study was
      51.4%. The prevalence of acne among respondents was 82.9%, and was strongly age
      dependent with highest rates in the age groups of 13-15 and 16-19 years. The
      prevalence of pre-pubertal acne among participating girls and boys was 69.9% and
      73.6% respectively. The main risk factors of acne were facial hair growth in boys
      (OR = 4.9), menarche in girls (OR = 3.1), overweight/obesity (BMI >= 25 kg/m(2)
      at 18 years of age) (OR = 2.6), acne history from both parents (OR = 2.6) and
      from mother alone (OR = 2.1). We did not find any associations between acne and
      nutritional habits, smoking or alcohol consumption. The self-reported prevalence
      of acne among children who refused to take part in the study was lower than that
      among participants of the study. CONCLUSIONS: The overall prevalence of acne
      among schoolchildren is high and age-dependent. The onset of puberty,
      overweight/obesity and history of acne from both parents are the top risk factors
      for acne.

PMID- 23560568
TI  - Prediction of on-road driving ability after traumatic brain injury and stroke.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to examine the predictive value
      of widely used standardized neuropsychological tests in a clinical setting for on
      road driving performance in patients with cerebral stroke or traumatic brain
      injury (TBI), and to provide cut-off values for neuropsychological test results
      under which driving should not be recommended. METHODS: Data from 78 patients who
      had undergone comprehensive driving assessment after stroke or TBI were
      retrospectively included in the analysis. Patients underwent medical examination,
      neuropsychological testing and on-road assessment. Medical data, demographic
      variables and neuropsychological performance were used as predictors in a
      stepwise logistic regression analysis with pass/fail after the on-road test as
      the dependent variable. Receiver operating characteristic curve analysis was
      employed to select cut-off values for the tests that were significant predictors
      for on-road performance. RESULTS: Forty-three patients passed and 35 failed the
      on-road driving task. Logistic regression analysis revealed three significant
      neuropsychological tests (CalCap simple reaction time, Trail Making Test A,
      Grooved Pegboard) as predictors for on-road performance explaining 46% of the
      variance with an overall classification accuracy of 82.1%. Receiver operating
      characteristic curve analysis showed the following cut-off values: CalCap, 395
      ms; Trail Making Test A, 46 s; Grooved Pegboard, 97.5 s. CONCLUSION: The results
      suggest that driving ability after brain damage and cerebral disease with no
      severe neurological deficits can be measured with a few distinctive
      neuropsychological tests together with medical examination and on-road
      assessment. Cut-off scores are a useful supplement to normative data/scaled
      scores.

PMID- 23560569
TI  - Protein influence on charge-asymmetry of the primary donor in photosynthetic
      bacterial reaction centers containing a heterodimer: effects on photophysical
      properties and electron transfer.
AB  - The substantial electronic distinctions between bacteriochlorophyll (BChl) and
      its Mg-free analogue bacteriopheophytin (BPh) are exploited in two sets of
      Rhodobacter capsulatus reaction center (RC) mutants that contain a heterodimeric
      BChl-BPh primary electron donor (D). The BPh component of the M-heterodimer (Mhd)
      or L-heterodimer (Lhd) obtains from substituting a Leu for His M200 or for His
      L173, respectively. Lhd-beta and Mhd-beta RCs serve as the initial templates in
      the two mutant sets, where beta denotes that the L-side BPh acceptor (HL) has
      been replaced by a BChl (due to substituting His for Leu M212). Three variants
      each of Lhd-beta and Mhd-beta mutants were constructed: (1) a swap (denoted YF)
      of the native Phe (L181) and Tyr (M208) residues, which flank D and the nearby M-
      and L-side monomeric BChl cofactors, respectively, giving Tyr (L181) and Phe
      (M208); (2) addition of a hydrogen bond (denoted L131LH) to the ring V keto group
      of the L-macrocycle of D, via replacing the native Leu at L131 with His; (3) the
      combination of 1 and 2. A low yield of electron transfer (ET) to the M-side BPh
      (HM) is observed in all four Lhd-containing RCs. Comparison with the yield of ET
      to beta on the L-side shows that electron density on the L-macrocycle of D*
      favors ET to the M-side cofactors and vice versa. Increasing or decreasing the
      electronic asymmetry of D* via the YF, L131LH mutations or the combination
      results in consistent trends in the characteristics of the long-wavelength ground
      state absorption band of D, the rate constant of internal conversion of D* to the
      ground state, and the rate constants for ET to both the L- and M-side cofactors.
      A surprising correlation is that an increase in the charge asymmetry in D* not
      only increases the D* internal-conversion rate constant, but also the rate
      constants for ET to both the L- and M-side cofactors, spanning time scales of
      tens of picoseconds to several nanoseconds. The YF swap has a previously
      unrecognized effect on the electronic asymmetry of D*, resulting in increased
      charge asymmetry for the Mhd and decreased charge asymmetry for the Lhd. This
      result indicates that the native Tyr (M208) and Phe (L181) in the wild-type RC
      promote an electron distribution in P* that is the reverse of that favorable for
      ET to the photoactive L-branch. This conclusion reinforces the view that the
      native configuration of these residues promotes ET to the L branch primarily by
      poising the free energies of the charge-separated states. Overall, this work
      addresses the extent to which electronic couplings complement energetics in
      underpinning the directionality of ET in the bacterial RC.

PMID- 23560570
TI  - All-on-4 concept: a 3-dimensional finite element analysis.
AB  - The aim of this work was to study the biomechanical behavior of an All-on-4
      implant-supported prosthesis through a finite element analysis comparing 3
      different tilt degrees of the distal implants. Three-dimensional finite element
      models of an edentulous maxilla restored with a prosthesis supported by 4
      implants were reconstructed to carry out the analysis. Three distinct
      configurations, corresponding to 3 tilt degrees of the distal implants (15
      degrees , 30 degrees , and 45 degrees ) were subjected to 4 loading simulations.
      The von Mises stresses generated around the implants were localized and
      quantified for comparison. Negligible differences in von Mises stress values were
      found in the comparison of the 15 degrees  and 30 degrees  models. From a stress
      level viewpoint, the 45 degrees  model was revealed to be the most critical for
      peri-implant bone. In all the loading simulations, the maximum stress values were
      always found at the neck of the distal implants. The stress in the distal
      implants increased in the apical direction as the tilt degree increased. The
      stress location and distribution patterns were very similar among the evaluated
      models. The increase in the tilt degree of the distal implants was proportional
      to the increase in stress concentration. The 45 degrees  model induced higher
      stress values at the bone-implant interface, especially in the distal aspect,
      than the other 2 models analyzed. 

PMID- 23560571
TI  - Peptide-directed preparation and X-ray structural study of Au nanoparticles on
      titanium surfaces.
AB  - We report the peptide-directed preparation and X-ray structural study of
      biofunctionalized Au nanoparticles (NPs) deposited on Ti surfaces. Au NPs were
      prepared by reduction of Au(3+) compound onto HCl-refreshed Ti in the presence of
      thiol-functionalized small peptides. A modified extended X-ray absorption fine
      structure (EXAFS) technique, equipped with a rotating-stage and glancing-angle
      setup, was able to more sensitively detect the structure and bonding of Au NPs on
      Ti with low surface coverage. It was found that the use of the tripeptide
      glutathione (GSH) results in smaller NP size when compared to N-(2-mercapto
      propionyl) glycine (MPG), a pseudodipeptide, over a wide range of Au/peptide
      molar ratios (20:1, 10:1, 5:1, and 2:1). By varying the ligand concentration, the
      Au NP structure in both systems can be controlled, generating nanocrystals,
      nanoclusters, and Au-thiolate polymer, which is unique for substrate-supported NP
      synthesis. This work presents a facile preparation of Au-peptide nanoparticles on
      biocompatible surfaces, and illustrates the high sensitivity of this modified
      EXAFS technique for structural studies of substrate-supported nanoparticles with
      low coverage.

PMID- 23560572
TI  - High-mobility pyrene-based semiconductor for organic thin-film transistors.
AB  - Numerous conjugated oligoacenes and polythiophenes are being heavily studied in
      the search for high-mobility organic semiconductors. Although many researchers
      have designed fused aromatic compounds as organic semiconductors for organic thin
      film transistors (OTFTs), pyrene-based organic semiconductors with high
      mobilities and on-off current ratios have not yet been reported. Here, we
      introduce a new pyrene-based p-type organic semiconductor showing liquid crystal
      behavior. The thin film characteristics of this material are investigated by
      varying the substrate temperature during the deposition and the gate dielectric
      condition using the surface modification with a self-assembled monolayer, and
      systematically studied in correlation with the performances of transistor devices
      with this compound. OTFT fabricated under the optimum deposition conditions of
      this compound, namely, 1,6-bis(5'-octyl-2,2'-bithiophen-5-yl)pyrene (BOBTP) shows
      a high-performance transistor behavior with a field-effect mobility of 2.1 cm(2)
      V(-1) s(-1) and an on-off current ratio of 7.6 * 10(6) and enhanced long-term
      stability compared to the pentacene thin-film transistor.

PMID- 23560573
TI  - Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot
      study with preliminary data on safety, body weight, and energy metabolism.
AB  - OBJECT: Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has
      been suggested as a potential treatment for intractable obesity. The authors
      present the 2-year safety results as well as early efficacy and metabolic effects
      in 3 patients undergoing bilateral LHA DBS in the first study of this approach in
      humans. METHODS: Three patients meeting strict criteria for intractable obesity,
      including failed bariatric surgery, underwent bilateral implantation of LHA DBS
      electrodes as part of an institutional review board- and FDA-approved pilot
      study. The primary focus of the study was safety; however, the authors also
      received approval to collect data on early efficacy including weight change and
      energy metabolism. RESULTS: No serious adverse effects, including detrimental
      psychological consequences, were observed with continuous LHA DBS after a mean
      follow-up of 35 months (range 30-39 months). Three-dimensional nonlinear
      transformation of postoperative imaging superimposed onto brain atlas anatomy was
      used to confirm and study DBS contact proximity to the LHA. No significant weight
      loss trends were seen when DBS was programmed using standard settings derived
      from movement disorder DBS surgery. However, promising weight loss trends have
      been observed when monopolar DBS stimulation has been applied via specific
      contacts found to increase the resting metabolic rate measured in a respiratory
      chamber. CONCLUSIONS: Deep brain stimulation of the LHA may be applied safely to
      humans with intractable obesity. Early evidence for some weight loss under
      metabolically optimized settings provides the first "proof of principle" for this
      novel antiobesity strategy. A larger follow-up study focused on efficacy along
      with a more rigorous metabolic analysis is planned to further explore the
      benefits and therapeutic mechanism behind this investigational therapy.

PMID- 23560575
TI  - Deep brain stimulation and obesity.

PMID- 23560574
TI  - Results of the NeuroBlate System first-in-humans Phase I clinical trial for
      recurrent glioblastoma: clinical article.
AB  - OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment
      for glioma; however, its development was limited due to technical issues. The
      NeuroBlate System incorporates several technological advances to overcome these
      drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing
      the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme
      (rGBM). METHODS: Adults with suspected supratentorial rGBM of 15- to 40-mm
      dimension and a Karnofsky Performance Status score of >= 60 were eligible. After
      confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side
      firing laser probe. Treatment was monitored using real-time MRI thermometry, and
      proprietary software providing predictive thermal damage feedback was used by the
      surgeon, along with control of probe rotation and depth, to tailor tissue
      coagulation. An external data safety monitoring board determined if toxicity at
      lower levels justified dose escalation. RESULTS: Ten patients were treated at the
      Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals-Case
      Medical Center). Their average age was 55 years (range 34-69 years) and the
      median preoperative Karnofsky Performance Status score was 80 (range 70-90). The
      mean tumor volume was 6.8 +/- 5 cm(3) (range 2.6-19 cm(3)), the percentage of
      tumor treated was 78% +/- 12% (range 57%-90%), and the conformality index was
      1.21 +/- 0.33 (range 1.00-2.04). Treatment-related necrosis was evident on MRI
      studies at 24 and 48 hours. The median survival was 316 days (range 62-767 days).
      Three patients improved neurologically, 6 remained stable, and 1 worsened.
      Steroid-responsive treatment-related edema occurred in all patients but one.
      Three had Grade 3 adverse events at the highest dose. CONCLUSIONS: NeuroBlate
      represents new technology for delivering laser interstitial thermal therapy,
      allowing controlled thermal ablation of deep hemispheric rGBM. CLINICAL TRIAL
      REGISTRATION NO.: NCT00747253 ( ClinicalTrials.gov ).

PMID- 23560576
TI  - Editorial: Glioblastoma multiforme and laser interstitial thermal therapy.

PMID- 23560577
TI  - Molecular oncogenesis of craniopharyngioma: current and future strategies for the
      development of targeted therapies.
AB  - Craniopharyngiomas are benign intracranial tumors that arise in the suprasellar
      and intrasellar region in children and adults. They are associated with
      calcification on neuroimaging, endocrinopathies, vision problems, and recurrence
      following subtotal resection. Molecular studies into their genetic basis have
      been limited, and therefore targeted medical therapies for this tumor have eluded
      physicians. With the discovery of aberrant Wnt/beta-catenin pathway signaling in
      the pathogenesis of the most common subtype of craniopharyngioma
      (adamantinomatous), the identification of candidate genes and proteins implicated
      in this cascade provide attractive targets for future therapies. The recent
      development of a genetically engineered animal model of this tumor may also serve
      as a platform for evaluating potential therapies prior to clinical trials in
      humans. Advances in understanding the molecular pathogenesis of tumor recurrence
      have also been made, providing clues to develop adjuvant and neoadjuvant
      therapies to couple with tumor resection for optimal response rates. Finally,
      advances in genomic technologies and next-generation sequencing will underlie the
      translation of these genetic and molecular studies from the bench to clinical
      practice. In this review, the authors present an analysis of the molecular
      oncogenesis of craniopharyngioma and current directions in the development of
      novel therapies for these morbid, yet poorly understood brain tumors. 

PMID- 23560578
TI  - In vivo embolization of lateral wall aneurysms in canines using the liquid-to
      solid gelling PPODA-QT polymer system: 6-month pilot study.
AB  - OBJECT: Over the past 20 years, endovascular embolization has become the
      preferred method of treating cerebral aneurysms. While there are many embolic
      devices on the market, none is ideal. In this study the authors investigated the
      use of a liquid-to-solid gelling polymer system-that is, poly(propylene glycol)
      diacrylate and pentaerythritol tetrakis (3-mercaptopropionate) (PPODA-QT)-to
      embolize in vivo aneurysms over a 6-month period. METHODS: Experimental aneurysms
      were created in the carotid arteries of 9 canines. Aneurysms were embolized with
      the polymer only (PPODA-QT, 3 dogs), filled with PPODA-QT after placement of a
      "framing" platinum coil (coil+PPODA-QT, 3 dogs), or packed with platinum coils
      (coils only, 3 dogs). Aneurysm occlusion was angiographically monitored
      immediately and 6 months after embolization. After 6 months, the ostial regions
      of explanted aneurysms were assessed macroscopically and histologically. RESULTS:
      All aneurysms showed 100% angiographic occlusion at 6 months, but turbulent blood
      flow was observed in 1 coils-only sample. Ostial regions of explanted coils-only
      aneurysms showed neointimal tissue surrounding individual coils but no continuous
      tissue layer over the aneurysm neck. All PPODA-QT aneurysms displayed smooth
      ostial surfaces, but 2 of 3 coil+PPODA-QT aneurysms showed polymer (unassociated
      with the coil) protruding into the vessel lumen, contributing to rough ostial
      surfaces. Neointimal tissue was present in PPODA-QT and coil+PPODA-QT aneurysms
      and covered smooth ostial surfaces more completely than in coils-only aneurysms.
      CONCLUSIONS: This study compared neointimal tissue overgrowth in the ostium of
      experimental aneurysms embolized with PPODA-QT, PPODA-QT plus a framing coil, or
      coils alone. The coils-only and coil+PPODA-QT groups showed rough and
      discontinuous ostial surfaces, which hindered neointimal tissue coverage. The
      PPODA-QT aneurysms consistently produced smooth ostial surfaces that facilitated
      more complete neointimal tissue coverage over aneurysm necks.

PMID- 23560579
TI  - Extracting and synthesizing information from a literature review.

PMID- 23560580
TI  - Using the thoughts on teen parenting survey to determine the impact of Wise Guys.
AB  - PURPOSE: The purpose of this project was to determine if the Wise Guys program
      influences young men's perceptions of the impact a teen birth would have on their
      lives in the areas of relationships, vocation, and personal life. DESIGN AND
      METHODS: The Wise Guys program was implemented with 70 adolescent males. The
      Thoughts on Teen Parenting Survey was used to determine participants' perceptions
      of the costs and rewards associated with teen parenting. RESULTS: Data, analyzed
      using paired t-tests, demonstrated that Wise Guys was effective in reinforcing
      less positive perceptions of teen parenting. PRACTICE IMPLICATIONS: Wise Guys
      offers an important strategy to impact young men's perceptions about the teen
      parenting experience and provides one means to promote responsible sexual
      behavior in teen men.

PMID- 23560581
TI  - A guided feeding intervention for mothers of preterm infants: two case studies.
AB  - PURPOSE: The purpose of this study was to determine how mothers of preterm
      infants perceive the feasibility and acceptability of a guided feeding
      intervention. DESIGN AND METHODS: In this multiple case study design, feasibility
      was assessed by retention of participants through all intervention sessions.
      Acceptability was assessed with a semi-structured interview. RESULTS:
      Participants found the intervention useful for demonstrating and explaining
      behaviors that facilitate feeding, and helpful in dispelling previous, erroneous
      understandings about infant behaviors. PRACTICE IMPLICATIONS: The results are
      encouraging. The intervention was found to be both feasible and acceptable. The
      effectiveness of this intervention needs to be assessed in a randomized
      controlled trial.

PMID- 23560582
TI  - Effect of distraction on children's pain during intravenous catheter insertion.
AB  - PURPOSE: This study examined the effect of pressing a soft ball during
      intravenous catheter insertion (IVCI) on the intensity of pain in children ages 4
      6 years. DESIGN AND METHODS: In this quasi-experimental study, children in the
      intervention group were asked to press a soft ball with the opposite hand during
      IVCI and to immediately mark the Wong-Baker FACES Pain Rating Scale. RESULTS:
      There was a significant difference in the intensity of pain between the control
      group (n = 30) and the intervention group (n = 30; p =.012). PRACTICE
      IMPLICATIONS: Pressing a soft ball during IVCI may be an easily accessed,
      inexpensive, and effective technique to control or reduce pain in young children.

PMID- 23560583
TI  - Residual newborn screening samples for research: parental information needs for
      decision-making.
AB  - PURPOSE: The purpose of this research was to identify what types of information
      expectant parents want to make a decision about the use of their babies' residual
      dried blood specimens for research. DESIGN AND METHODS: Three focus groups were
      conducted with pregnant women and their partners and one focus group with
      prenatal healthcare providers and educators. RESULTS: Eleven categories of
      information needs were identified within each focus group. PRACTICE IMPLICATIONS:
      Providing sufficient information for parents to make informed choices will be
      essential to future research with residual dried blood specimens and to maintain
      public trust with the growing applications of this important public health
      program.

PMID- 23560584
TI  - Efficacy of petrolatum jelly for the prevention of diaper rash: a randomized
      clinical trial.
AB  - PURPOSE: To assess the efficacy of petrolatum jelly for the prevention of diaper
      rash and to evaluate the relationship between the occurrence of diaper rash and
      certain treatments and type of nutrition. DESIGN AND METHODS: A randomized
      clinical trial was carried out with two parallel groups (n = 213) at the neonatal
      care unit of Donostia University Hospital in San Sebastian, Guipuzcoa Province,
      Spain. RESULTS: There was a lower incidence of diaper rash in the experimental
      group with petrolatum jelly (17.1%) than the control group (22.2%), but the
      difference was not statistically significant (p =.39). The use of antibiotics and
      oral 50% glucose as well as an increased number of stools are associated with a
      higher incidence of diaper rash, while breastfeeding and phototherapy are
      protective factors. PRACTICE IMPLICATIONS: Prevention is strengthened by a better
      understanding of the risk factors.

PMID- 23560585
TI  - Integrating illness concerns into cognitive behavioral therapy for children and
      adolescents with inflammatory bowel disease and co-occurring anxiety.
AB  - PURPOSE: To examine the feasibility and preliminary benefits of an integrative
      cognitive behavioral therapy (CBT) with adolescents with inflammatory bowel
      disease and anxiety. DESIGN AND METHODS: Nine adolescents participated in a CBT
      program at their gastroenterologist's office. Structured diagnostic interviews,
      self-report measures of anxiety and pain, and physician-rated disease severity
      were collected pretreatment and post-treatment. RESULTS: Postintervention, 88% of
      adolescents were treatment responders, and 50% no longer met criteria for their
      principal anxiety disorder. Decreases were demonstrated in anxiety, pain, and
      disease severity. PRACTICE IMPLICATIONS: Anxiety screening and a mental health
      referral to professionals familiar with medical management issues is important.

PMID- 23560586
TI  - Development of an in-home standardized end-of-life treatment program for
      pediatric patients dying of brain tumors.
AB  - PURPOSE: To evaluate an end-of-life (EOL) program related to specific outcomes
      (i.e., number of hospitalizations and place of death) for children with brain
      tumors. DESIGN AND METHODS: From 1990 to 2005, a retrospective chart review was
      performed related to specified outcomes for 166 children with admission for
      pediatric brain tumors. RESULTS: Patients who received the EOL program were
      hospitalized less often (n = 114; chi-square = 5.001 with df = 1, p <.05) than
      patients who did not receive the program. PRACTICE IMPLICATIONS: An EOL program
      may improve symptom management and decrease required hospital admissions for
      children with brain tumors.

PMID- 23560587
TI  - Improved accuracy of discrimination between IgM multiple myeloma and Waldenstrom
      macroglobulinaemia by testing for MYD88 L265P mutations.

PMID- 23560588
TI  - Rh(III)-catalyzed addition of alkenyl C-H bond to isocyanates and intramolecular
      cyclization: direct synthesis 5-ylidenepyrrol-2(5H)-ones.
AB  - The rhodium-catalyzed addition of an alkenyl C-H bond to isocyanates via sp(2) C
      H bond activation followed by an intramolecular cyclization is described. This
      atom-economic and catalytic reaction affords a simple and straightforward access
      to biologically relevant 5-ylidene pyrrol-2(5H)-ones and can be carried out under
      mild and neutral conditions in the absence of any additives and environmentally
      hazardous waste production.

PMID- 23560589
TI  - Osteoblastic and osteoclastic differentiation on SLA and hydrophilic modified SLA
      titanium surfaces.
AB  - PURPOSE: We evaluated the activities of both osteoblastic and osteoclastic
      differentiation on sandblasted/acid etched (SLA), hydrophilic SLA surfaces
      (modSLA) and pretreatment titanium (PT). MATERIAL AND METHODS: The osteoblastic
      differentiation was evaluated by alkaline phosphatase analysis and Alizarin Red S
      staining, and the expression of bone-related proteins, alkaline phosphatase
      (ALP), runt-related transcription factor 2 (Runx2), osteopontin (OPN), and
      osteocalcin (OCN), was investigated by reverse transcriptase-polymerase chain
      reaction (RT-PCR). Primary mice monocytes were expanded and differentiated in the
      presence of macrophage-colony stimulating factor (M-CSF), and osteoclastic
      differentiation was evaluated by actin ring formation assay and tartrate
      resistant acid phosphatase (TRAP) activity assay. Real-time PCR tests were
      performed to investigate the expression of gene mRNA expression levels in
      osteoclast cells. RESULT: Differentiation of osteoblasts in the Alizarin Red S
      test staining and ALP assay was significantly increased in the modSLA surface.
      The preceding results were supported by the result of RT-PCR for the expression
      of Runx2, OPN, and OCN. As for osteoclastic activity, differentiated osteoclasts
      rarely existed on the SLA and modSLA surface with actin ring. The results of real
      time PCR and TRAP activity supported the preceding results. CONCLUSION: It may be
      concluded that the modSLA surface promotes osteogenic effect and prevents
      osteoclastic differentiation. Promotion of osteoblastic proliferation after a
      short-term cell culture might be responsible for stimulated bone regeneration
      implying that early loading may be possible. Also, the anti-osteoclastic effect
      of the modSLA surface may contribute to maintenance of the marginal bone level of
      dental implants, implying long-term stability would be provided by this surface
      technology. The modSLA surface may not only make early loading possible but
      possibly reduce marginal bone loss during the maintenance phase.

PMID- 23560590
TI  - A systematic review and meta-analysis of laparoscopic vs open restorative
      proctocolectomy.
AB  - AIM: The benefits of a laparoscopic approach to restorative proctocolectomy (RPC)
      are controversial. The aim of this meta-analysis was to compare the outcome
      following laparoscopic and open RPC, with particular attention to adverse events
      and long-term function. METHOD: A systematic search of the MEDLINE, EMBASE and
      Ovid databases was performed for studies published until March 2012. The primary
      end-point was long-term function. Secondary end-points were intra-operative
      details, short-term postoperative outcome and postoperative adverse events.
      Weighted mean difference (WMD) and odds ratio (OR) were calculated using
      fixed/random effect meta-analytic techniques. RESULTS: The final analysis
      included 27 comparative studies of 2428 patients, of whom 1097 (45.1%) underwent
      laparoscopic surgery. A laparoscopic approach was associated with a significantly
      longer operation time (WMD 70.1 min, P < 0.001), shorter length of hospital stay
      (WMD -1.00 day, P < 0.001), reduced intra-operative blood loss (WMD -89.10 ml, P
      < 0.001) and a lower incidence of wound infection (OR 0.60, P < 0.005). No
      significant differences were observed in the rate of pouch failure. Although
      there was no significant difference in the number of daily bowel movements (OR
      0.04, P = 0.950), laparoscopic surgery led to fewer nocturnal bowel movements
      (WMD -1.14, P < 0.001) and reduced pad usage during the day (OR 0.22, P < 0.001)
      and night (OR 0.33, P < 0.001). The post hoc power to detect differences in
      adverse event rates ranged from 5% to 42%. CONCLUSION: Laparoscopic and open
      approaches to RPC produced equivalent adverse event rates and long-term
      functional results. However, the present evidence is underpowered to detect true
      differences in adverse event rates.

PMID- 23560591
TI  - Depressive symptoms in first episode psychosis: a one-year follow-up study.
AB  - BACKGROUND: Depressive symptoms are common in patients with first episode
      psychosis (FEP) and have serious consequences for them. The main aims of this
      study were to examine the course of depression in FEP patients and explore
      whether any patient characteristics at baseline predicts depressive symptoms
      after one year. METHOD: A total of 198 FEP patients with schizophrenia spectrum
      disorders were assessed for depressive symptoms with Calgary Depression Scale for
      Schizophrenia (CDSS) at baseline and 127 were followed for one year. A CDSS score
      [greater than or equal to] 6 was used as a cut-off score for depression. RESULTS:
      Approximately 50% of the patients were depressed (CDSS[greater than or equal
      to]6) at baseline. At follow-up approximately 35% had depression. The course of
      depressive symptoms varied, 26% was depressed at both baseline and follow-up, 9%
      became depressed during the follow-up, 22% remitted from depression during the 12
      months and 43% was neither depressed at baseline nor at follow-up. Poor childhood
      social functioning, long duration of untreated psychosis (DUP) and depressive
      symptoms at baseline predicted depression at 12 months follow-up. CONCLUSION:
      Depressive symptoms are frequent in the first year after onset of psychosis.
      Patients with poor social functioning in childhood, long DUP and depressive
      symptoms at baseline are more prone to have depressive symptoms after one year.
      These patients should be identified and proper treatment provided.

PMID- 23560593
TI  - (alpha-DT-TTF)2[Au(mnt)2]: a weakly disordered molecular spin-ladder system.
AB  - The synthesis and characterization of (alpha-DT-TTF)2[Au(mnt)2] is reported. The
      magnetic properties of this new salt show that it is still a rare example of an
      organic spin-ladder. (alpha-DT-TTF)2[Au(mnt)2] shares the same ladder structure
      of the DT-TTF and ETT-TTF analogues, and its room temperature conductivity is ~2
      S/cm. Despite the observed donor orientation disorder associated with the
      thiophenic sulfur atoms, the intermolecular interactions between donor units,
      calculated using the extended Huckel approximation and a double-xi basis set,
      show that the interaction values do not depend on the configuration of the sulfur
      atom on the thiophenic ring. The insensitivity of the spin-ladder magnetic
      properties to the donor molecular disorder in (alpha-DT-TTF)2[Au(mnt)2] is a
      direct consequence of the negligible contribution of the disordered thiophenic
      sulfur atom to the HOMO. In the related donor ETT-TTF, this contribution is
      significant and destroys the magnetic interactions, and no spin-ladder is
      observed. This compound not only enlarges the number of organic spin-ladder
      systems in this series of closely related compounds but also provides an
      interesting example of weakly disordered molecular spin-ladder system.

PMID- 23560592
TI  - Distinctive effects of domain deletions on the manganese-dependent DNA polymerase
      and DNA phosphorylase activities of Mycobacterium smegmatis polynucleotide
      phosphorylase.
AB  - Polynucleotide phosphorylase (PNPase) plays synthetic and degradative roles in
      bacterial RNA metabolism; it is also suggested to participate in bacterial DNA
      transactions. Here we characterize and compare the RNA and DNA modifying
      activities of Mycobacterium smegmatis PNPase. The full-length (763-aa) M.
      smegmatis PNPase is a homotrimeric enzyme with Mg(2+)*PO(4)-dependent RNA 3'
      phosphorylase and Mg(2+)*ADP-dependent RNA polymerase activities. We find that
      the enzyme is also a Mn(2+)*dADP-dependent DNA polymerase and a Mn(2+)*PO(4)
      dependent DNA 3'-phosphorylase. The Mn(2+)*DNA and Mg(2+)*RNA end modifying
      activities of mycobacterial PNPase are coordinately ablated by mutating the
      putative manganese ligand Asp526, signifying that both metals likely bind to the
      same site on PNPase. Deletions of the C-terminal S1 and KH domains of
      mycobacterial PNPase exert opposite effects on the RNA and DNA modifying
      activities. Subtracting the S1 domain diminishes RNA phosphorylase and polymerase
      activity; simultaneous deletion of the S1 and KH domains further cripples the
      enzyme with respect to RNA substrates. By contrast, the S1 and KH domain
      deletions enhance the DNA polymerase and phosphorylase activity of mycobacterial
      PNPase. We observe two distinct modes of nucleic acid binding by mycobacterial
      PNPase: (i) metal-independent RNA-specific binding via the S1 domain, and (ii)
      metal-dependent binding to RNA or DNA that is optimal when the S1 domain is
      deleted. These findings add a new dimension to our understanding of PNPase
      specificity, whereby the C-terminal modules serve a dual purpose: (i) to help
      capture an RNA polynucleotide substrate for processive 3' end additions or
      resections, and (ii) to provide a specificity filter that selects against a DNA
      polynucleotide substrate.

PMID- 23560594
TI  - Chemotherapy in the management of brain metastases: the emerging role of
      fotemustine for patients with melanoma and NSCLC.
AB  - INTRODUCTION: An estimated 20 - 40% of cancer patients will develop brain
      metastases that are the most common intracranial tumors in adults. Patients with
      cerebral metastases represent a variegate group where selection of the most
      appropriate treatment depends on many patient- and disease-related factors. The
      impact of therapeutic option on overall survival is lacking and it is important
      to consider quality of life (QOL) when treating patients with brain metastases.
      AREAS COVERED: A considerable proportion of patients are treated with palliative
      approaches such as whole-brain radiotherapy. The role of chemotherapy was limited
      in the past. Recently, several chemotherapeutic agents have been identified as
      potentially useful. This article examines the pharmacokinetics, efficacy and
      safety and tolerability of fotemustine (FTM) for the management of patients with
      cerebral metastasis from melanoma and non-small cell lung cancer (NSCLC). EXPERT
      OPINION: FTM is a third-generation nitrosourea that has proved its efficacy on
      brain metastases of melanoma and showed promising results for the treatment of
      brain metastasis of NSCLC because of its ability to pass the blood-brain barrier.

PMID- 23560595
TI  - Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.
AB  - In a retrospective cohort study undertaken in 12 European countries, 249 female
      narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33)
      completed a self-administrated questionnaire regarding pregnancy and childbirth.
      The cohort was divided further into patients whose symptoms of narcolepsy started
      before or during pregnancy (308 pregnancies) and those in whom the first symptoms
      of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy
      during pregnancy were older during their first pregnancy (P < 0.001) and had a
      higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during
      pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More
      patients with narcolepsy-cataplexy during pregnancy had impaired glucose
      metabolism and anaemia. Three patients experienced cataplexy during delivery. The
      rate of caesarean sections was higher in the narcolepsy-cataplexy group compared
      to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of
      neonates were within the normal range and did not differ across groups. Neonatal
      care was affected adversely by symptoms of narcolepsy in 60.1% of those with
      narcolepsy during pregnancy. This study reports more obstetric complications in
      patients with narcolepsy-cataplexy during pregnancy; however, these were not
      severe. This group also had a higher BMI and higher incidence of impaired glucose
      metabolism during pregnancy. Caesarian section was conducted more frequently in
      narcolepsy-cataplexy patients, despite cataplexy being a rare event during
      delivery. Furthermore, symptoms of narcolepsy may render care of the infant more
      difficult. 

PMID- 23560596
TI  - Prevalence of QTc interval changes in acute psychiatric care: a cross-sectional
      study.
AB  - INTRODUCTION: In a case series we examined the prevalence and incidence of QT
      changes during a 1-week interval in hospitalized patients in a general psychiatry
      ward during a 6-month period. METHOD: This cross-sectional study was done on
      electrocardiographic QT interval of patients admitted to the Psychiatric
      Department of Taleghani Hospital during a 6-month period excluding subjects with
      underlying cause of QT prolongation. RESULTS: Admission and follow-up
      electrocardiograms of 27 men and 47 women were studied, there was significant QT
      prolongation during hospitalization (P value 0.001) in approximately 30% of
      subjects, irrespective of type of administered medication. CONCLUSION: Pro
      arrhythmic changes as reflected in QTc prolongation and QTc dispersion in
      electrocardiograms are common in patients admitted in psychiatric wards
      irrespective of type of therapy and should be screened and followed by serial
      electrocardiograms to minimize untoward cardiac outcomes.

PMID- 23560597
TI  - Dissecting the deep biosphere: retrieving authentic microbial communities from
      packer-isolated deep crystalline bedrock fracture zones.
AB  - Deep fracture zones in Finnish crystalline bedrock have been isolated for long,
      the oldest fluids being tens of millions of years old. To accurately measure the
      native microbial diversity in fracture-zone fluids, water samples were obtained
      by isolating the borehole fraction spanning a deep subsurface aquifer fracture
      zone with inflatable packers (500 and 967 m) or by pumping fluids directly from
      the fracture zone. Sampling frequency was examined to establish the time required
      for the space between packers to be flushed and replaced by indigenous fracture
      fluids. Chemical parameters of the fluid were monitored continuously, and samples
      were taken at three points during the flushing process. Microbial communities
      were characterized by comparison of 16S ribosomal genes and transcripts and
      quantification of dsrB (dissimilatory sulfate reduction) gene. Results suggest
      that fracture-zones host microbial communities with fewer cells and lower
      diversity than those in the drill hole prior to flushing. In addition, each
      fracture zone showed a community composition distinct from that inhabiting the
      drill hole at corresponding depth. The highest diversity was detected from the
      967-m fracture zone. We conclude that the applied packer method can successfully
      isolate and sample authentic microbial fracture-zone communities of deep bedrock
      environments.

PMID- 23560598
TI  - Is fungal foot infection the initiating and maintaining cause of knee
      osteoarthritis?
AB  - So far fungal foot infection (FFI) has been considered as troubling, however, not
      dangerous, by the general public as well as doctors. Nevertheless, new immunology
      information and anatomy dispositions led us to the distinct suspicions. We
      propose a FFI-induced knee joint osteoarthritis (OA) model. We suppose repeated
      recurrences of fungal foot disease to be the initiating immunology impulse. The
      aim of the work is to introduce a new model and to determine antigen epitopes
      initiating and maintaining the knee OA using computer simulation. Freely
      accessible immunological databases and servers were used in this search.
      Presentable antigen epitopes in Trichophyton rubrum dermatophyte products were
      identified for molecules of the six most abundant alleles of DRB1 locus of human
      major histocompatibility complex. Subsequently, similar sequences in human joint
      peptides (collagens, aggrecan and others) were matched to these antigen epitopes
      by a comparative program. A number of pairs with very similar fungal and joint
      peptide sequences, supposed to initiate and maintain the knee OA antigen
      epitopes, were found. A FFI-induced knee joint OA model is shown to the medical
      community which can initiate further discussion, research and practical
      verification. 

PMID- 23560599
TI  - A synthetic receptor for asymmetric dimethyl arginine.
AB  - Dynamic combinatorial chemistry was utilized to identify a novel small molecule
      receptor, A2D, for asymmetric dimethyl arginine (aRMe2), which is a post
      translational modification (PTM) in proteins. It is known to play a role in a
      number of diseases, including spinal muscular atrophy, leukemia, lymphoma, and
      breast cancer. The receptor exhibits 2.5-7.5-fold selectivity over the isomeric
      symmetric dimethyl arginine, depending on the surrounding sequence, with binding
      affinities in the low micromolar range. The affinity and selectivity of A2D for
      the different methylated states of Arg parallels that of proteins that bind to
      these PTMs. Characterization of the receptor-PTM complex indicates that cation-pi
      interactions provide the main driving force for binding, loosely mimicking the
      binding mode found in the recognition of dimethyl arginine by native protein
      receptors.

PMID- 23560600
TI  - A systematic review of combination therapy with stimulants and atomoxetine for
      attention-deficit/hyperactivity disorder, including patient characteristics,
      treatment strategies, effectiveness, and tolerability.
AB  - OBJECTIVE: The purpose of this article was to systematically review the
      literature on stimulant and atomoxetine combination therapy, in particular: 1)
      Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD)
      given combination therapy, 2) treatment strategies used, 3) efficacy and
      effectiveness, and 4) safety and tolerability. METHODS: Literature databases
      (MEDLINE((r)), EMBASE, Cochrane Central Register of Controlled Trials, Science
      Citation Index Expanded, and SciVerse Scopus) were systematically searched using
      prespecified criteria. Publications describing stimulant and atomoxetine
      combination therapy in patients with ADHD or healthy volunteers were selected for
      review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy,
      or other psychiatric/neurologic diseases that could confound ADHD symptom
      assessment, or other concomitant medication(s) to treat ADHD symptoms. RESULTS:
      Of the 16 publications included for review, 14 reported findings from 3
      prospective studies (4 publications), 7 retrospective studies, and 3 narrative
      reviews/medication algorithms of patients with ADHD. The other two publications
      reported findings from two prospective studies of healthy volunteers. The main
      reason for prescribing combination therapy was inadequate response to previous
      treatment. In the studies of patients with ADHD, if reported, 1) most patients
      were children/adolescents and male, and had a combined ADHD subtype; 2)
      methylphenidate was most often used in combination with atomoxetine for treatment
      augmentation or switch; 3) ADHD symptom control was improved in some, but not
      all, patients; and 4) there were no serious adverse events. CONCLUSIONS:
      Published evidence of the off-label use of stimulant and atomoxetine combination
      therapy is limited because of the small number of publications, heterogeneous
      study designs (there was only one prospective, randomized controlled trial),
      small sample sizes, and geographic bias. Existing evidence suggests, but does not
      confirm, that this drug combination may benefit some, but not all, patients who
      have tried several ADHD medications without success.

PMID- 23560601
TI  - The association between medication for attention-deficit/hyperactivity disorder
      and cancer.
AB  - OBJECTIVE: A study on chromosomal abnormalities has raised concerns that
      medication with methylphenidate (MPH) for attention-deficit/hyperactivity
      disorders (ADHD) might increase the risk of cancer. We performed a rigorous test
      of the association between cancer and MPH and other drugs used for ADHD, based on
      data from nationwide Danish registers. METHODS: Data were linked from five
      registers containing information on a total of 21,186 patients with ADHD, their
      drug prescription rates, and associated cancer diagnoses between 1994 and 2010.
      The cohort included subgroups treated with MPH only, amphetamines only, other
      ADHD-specific drugs only, antidepressants only, antipsychotics only, mixed
      medication, and a control group of patients with ADHD who had never taken
      medication. Frequencies of cancer diagnoses in these groups were compared. In
      addition, hazard risk (HR) ratios for developing cancer, and survival rates in
      these subgroups, were analyzed. RESULTS: The mean observation time varied between
      1.3 and 10.8 years for the various drugs. Cancer rates in the total group
      amounted to 1.27 per 10 000 person-years before and to 4.33 per 10 000 person
      years after onset of treatment. The frequency of cancer was significantly higher
      (p = 0.05) after than before medication only in the antipsychotics subgroup.
      Furthermore, for mixed medication, the cancer frequency in a small subgroup was
      significantly higher (p < 0.05) after onset of medication than in the unmedicated
      subgroup. The Cox regression analysis indicated that none of the drugs
      represented risk factors, whereas higher dose (p < 0.001) and older age (p <
      0.05) were risk factors for developing cancer. CONCLUSIONS: The concern that
      children taking MPH and other drugs over long periods of time could be at a
      significant risk of developing cancer is not substantiated by these findings in a
      large and representative sample, which had been diagnosed and treated over a
      period of 17 years.

PMID- 23560602
TI  - Factors influencing parental decision making about stimulant treatment for
      attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a pediatric
      psychological condition commonly treated with stimulant medications. Negative
      media reports and stigmatizing societal attitudes surrounding the use of these
      medications make it difficult for parents of affected children to accept
      stimulant treatment, despite it being first line therapy. OBJECTIVE: The purpose
      of this study was to identify factors that influence parental decision making
      regarding stimulant treatment for ADHD. METHODS: A systematic review of the
      literature was conducted to identify studies: 1) that employed qualitative
      methodology, 2) that highlighted treatment decision(s) about stimulant
      medication, 3) in which the decision(s) were made by the parent of a child with
      an official ADHD diagnosis, and 4) that examined the factors affecting the
      decision(s) made. Individual factors influencing parental treatment decision
      making, and the major themes encompassing these factors, were identified and
      followed by a thematic analysis. RESULTS: Eleven studies reporting on the
      experiences of 335 parents of children with ADHD were included. Four major themes
      encompassing influences on parents' decisions were derived from the thematic
      analysis performed: confronting the diagnosis, external influences, apprehension
      regarding therapy, and experience with the healthcare system. CONCLUSIONS: The
      findings of this systematic review reveal that there are multiple factors that
      influence parents' decisions about stimulant therapy. This information can assist
      clinicians in enhancing information delivery to parents of children with ADHD,
      and help reduce parental ambivalence surrounding stimulant medication use. Future
      work needs to address parental concerns about stimulants, and increase their
      involvement in shared decision making with clinicians to empower them to make the
      most appropriate treatment decision for their child.

PMID- 23560603
TI  - The effect of labour on the coagulation system in the term neonate.
AB  - The coagulation system of the foetus is markedly different from that of adults.
      To assess the influence of maternal age, mode of delivery and intrapartum events,
      and foetal gender and weight on the foetal coagulation system. Cord blood was
      collected from 154 healthy pregnant women, with gestational age 37 - 42 weeks at
      birth. Mann-Whitney test was used for analysis of binary data and continuous
      variables were analysed using Pearson's correlation coefficient. Mean cord blood
      levels of FVIII:C, VWF:Ag, VWF:CB, FIX, FXI, FXII and plasminogen were
      significantly higher in babies delivered after labour, compared to those
      delivered after an elective caesarean. Mean cord blood levels of FII (P = 0.003),
      FV (P = 0.009), FVII (P = 0.0004) and FX (P = 0.0009) were significantly lower in
      the babies with meconium stained liquor in labour, compared with those with clear
      liquor. Augmentation with oxytocin, instrumental delivery, did not affect any of
      the factor levels and duration of labour did not have an effect on the level of
      coagulation proteins in cord blood. This study provides valuable information
      about effect of labour on the coagulation system of the foetus. It is concluded
      that, in cord blood, the results of coagulation parameters in the newborn baby
      should be considered in light of mode of delivery and events of labour.

PMID- 23560604
TI  - Clupeid response to stressors: the influence of environmental factors on
      thiaminase expression.
AB  - Over the past five decades, a reproductive failure related to thiamine
      deficiency, referred to as thiamine deficiency complex (TDC), has been observed
      in valuable salmonine fishes in the Great Lakes and Finger Lakes in North America
      and the Baltic Sea in Europe. The cause of TDC has been linked to the consumption
      of clupeid fish, which contain high levels of a thiamine-destroying enzyme called
      thiaminase I (hereafter referred to as "thiaminase"). High activities of
      thiaminase have been reported from clupeids such as Alewife Alosa pseudoharengus,
      Gizzard Shad Dorosoma cepedianum and Atlantic (Baltic) Herring Clupea harengus,
      but no consistent explanation has accounted for the wide range of observed
      variation in levels of thiaminase in clupeids. Chronic stress can suppress the
      immune systems of Alewife and other fishes, thereby reducing the number of
      circulating white blood cells available to suppress bacteria. Because the
      presence of thiaminase has been associated with thiaminolytic bacteria isolated
      from Alewife viscera, we hypothesized that stressful conditions, which can
      potentially limit clupeid immune response or alter internal physiological
      conditions, could allow for thiaminase to be produced more efficiently by
      bacteria or thiaminolytic bacteria could proliferate, or both events could occur,
      resulting in a subsequent increase in thiaminolytic activity. In this study,
      Alewives and Gizzard Shad were exposed to severe winter temperatures and low food
      availability, respectively, in replicated pond experiments to evaluate the
      influence of stressful conditions on clupeid thiaminase activity. Though
      responses in circulating white blood cell counts and metrics of fish condition
      indicated that experimental treatments affected these clupeids, these effects
      were not related to increased thiaminase activity. The only significant treatment
      effect on clupeid thiaminase was an increase in mean thiaminase activity in
      Gizzard Shad from ponds where only high quality energy sources were available.
      These data indicate that variability in clupeid thiaminase may be related to diet
      composition.

PMID- 23560605
TI  - Anticoagulation for prevention and treatment of cancer-related venous
      thromboembolism.
AB  - The close relationship between malignancy and venous thromboembolism (VTE) is
      well established, with malignancy increasing VTE risk and accounting for a
      substantial proportion of presentations with VTE. Moreover, VTE impacts
      significantly on morbidity and mortality in cancer patients. Anticoagulation for
      prevention and treatment of VTE requires a patient-centred approach due to the
      heterogeneous patient population and inherent increased thrombotic and bleeding
      risks. In recent years, low molecular weight heparin (LMWH) injections have come
      to be the mainstay for treatment and prevention of cancer-related VTE. For
      treatment, this is usually administered for at least 6 months and continued in
      patients with active cancer or those receiving treatment for cancer. The use of
      LMWH for thromboprophylaxis in hospitalised cancer patients is also well
      accepted, but out-of-hospital prophylaxis remains contentious. The development of
      risk assessment models may help identify the patients at highest risk. The role
      of the new oral factor Xa and thrombin inhibitors in this setting remains to be
      determined.

PMID- 23560606
TI  - Deproteinized bovine bone mineral particles and osseointegration of implants
      without primary bone contact: an experimental study in dogs.
AB  - OBJECTIVES: To evaluate the influence on osseointegration of Deproteinized bovine
      bone mineral (DBBM) particles used to fill defects of at least 1 mm around
      implants having no primary contact with bone. MATERIAL AND METHODS: Premolars and
      first molars were extracted bilaterally from the mandible of six Labrador dogs.
      After 3 months of healing, mucoperiosteal full-thickness flaps were elevated, and
      one recipient site was prepared in the molar region of each hemi-mandible to
      place implants. These were installed with a deliberate circumferential and
      periapical space to the bone walls of 1.2 mm. All implants were stabilized with
      passive fixation plates to maintain the implants in situ and without any contact
      with the implant bed. The control sites were left to be filled with coagulum,
      while at the test sites, the residual gap was filled with DBBM. After 3 months of
      submerged healing, the animals were sacrificed. Ground sections were prepared and
      analyzed histomorphometrically. RESULTS: Mineralized bone-to-implant contact was
      4.0% and 3.9% for control and test sites, respectively. The width of the residual
      defects was 0.48 mm and 0.88 mm at the control and test sites, respectively. The
      percentage of implant surface covered by a layer of dense connective tissue of
      0.12 mm of width on average was 84.9% and 88.5% at the control and test sites,
      respectively. CONCLUSION: A minor and not predictable degree of contact or
      distance osteogenesis was obtained on the implant surface when primary contact of
      the implant surface with the implant bed had deliberately been avoided. DBBM
      grafting of the artificial gap did not favor osseointegration. Neither did it
      enhance the ability to bridge the gap with newly formed bone in an artificial
      defect wider than 1 mm.

PMID- 23560607
TI  - Unraveling the glyco-puzzle: glycan structure identification by capillary
      electrophoresis.
AB  - State-of-the-art high-resolution separation techniques play an important role in
      the full structural elucidation of glycans. Capillary electrophoresis (CE) offers
      a rapid yet simple method for exhaustive carbohydrate profiling. CE is a
      versatile analytical platform, which can be operated in several separation modes,
      simply by altering separation conditions during operation. For in-depth glycan
      structural analysis, CE has also gained significantly from the additional
      resolution introduced by complementary and orthogonal separation techniques such
      as ion exchange or hydrophilic interaction chromatography. Commercially available
      mass spectrometry (MS) interfaces have not only brought this information-rich
      detection technique within reach, but CE also represents an expedient highly
      efficient separation inlet for MS, capable of separating isobaric oligosaccharide
      isomers prior to MS detection and MS/MS fragmentation based identification. This
      Perspective gives a sophisticated impression of the versatility of capillary
      electrophoresis for deep structural elucidation of carbohydrates derived from
      glycoproteins of biomedical interest. Different separation modes for the analysis
      of both charged and neutral glycans, such as influencing electroosmotic flow,
      using complexation/interaction based secondary equilibria, and the use of charged
      and neutral labels are compared. The merits of introducing orthogonal and
      complementary techniques, such as exoglycosidase digestion arrays,
      analytical/preparative chromatography and mass spectrometric detection, extending
      the dynamic range and resolution of CE are all thoroughly discussed. 

PMID- 23560609
TI  - Oxamate is an alternative substrate for pyruvate carboxylase from Rhizobium etli.
AB  - Oxamate, an isosteric and isoelectronic inhibitory analogue of pyruvate, enhances
      the rate of enzymatic decarboxylation of oxaloacetate in the carboxyl transferase
      domain of pyruvate carboxylase (PC). It is unclear, though, how oxamate exerts a
      stimulatory effect on the enzymatic reaction. Herein, we report direct (13)C
      nuclear magnetic resonance (NMR) evidence that oxamate acts as a carboxyl
      acceptor, forming a carbamylated oxamate product and thereby accelerating the
      enzymatic decarboxylation reaction. (13)C NMR was used to monitor the PC
      catalyzed formation of [4-(13)C]oxaloacetate and subsequent transfer of (13)CO(2)
      from oxaloacetate to oxamate. In the presence of oxamate, the apparent K(m) for
      oxaloacetate is artificially suppressed (from 15 to 4-5 MUM). Interestingly, the
      steady-state kinetic analysis of the initial rates determined at varying
      concentrations of oxaloacetate and fixed concentrations of oxamate revealed
      initial velocity patterns inconsistent with a simple ping-pong-type mechanism.
      Rather, the patterns suggest the existence of an alternate decarboxylation
      pathway in which an unstable intermediate is formed. The steady-state kinetic
      analysis coupled with the normal (13)(V/K) kinetic isotope effect observed on C-4
      of oxaloacetate [(13)(V/K) = 1.0117 +/- 0.0005] indicates that the transfer of
      CO(2) from carboxybiotin to oxamate is the partially rate-limiting step of the
      enzymatic reaction. The catalytic mechanism proposed for the carboxylation of
      oxamate is similar to that proposed for the carboxylation of pyruvate, which
      occurs via the formation of an enol intermediate.

PMID- 23560608
TI  - Adolescent attachment security, family functioning, and suicide attempts.
AB  - Theories of suicidal behavior suggest that the desire to die can arise from
      disruption of interpersonal relationships. Suicide research has typically studied
      this from the individual's perspective of the quality/frequency of their social
      interactions; however, the field of attachment may offer another perspective on
      understanding an individual's social patterns and suicide risk. This study
      examined attachment along with broader family functioning (family adaptability
      and cohesion) among 236 adolescent psychiatric inpatients with (n = 111) and
      without (n = 125) histories of suicide attempts. On average, adolescents were 14
      years of age and Hispanic (69%). Compared to those without suicide attempts,
      adolescent attempters had lower self-reported maternal and paternal attachment
      and lower familial adaptability and cohesion. When comparing all three types of
      attachment simultaneously in the logistic regression model predicting suicide
      attempt status, paternal attachment was the only significant predictor. Suicide
      attempt group was also significantly predicted by self-rated Cohesion and
      Adaptability; neither of the parent ratings of family functioning were
      significant predictors. These findings are consistent with the predictions of the
      Interpersonal Theory of Suicide about social functioning and support the efforts
      to develop attachment-based interventions as a novel route towards suicide
      prevention.

PMID- 23560610
TI  - Anomalous origin of the right coronary artery from the pulmonary artery in a
      child with chest pain.

PMID- 23560611
TI  - Synthesis of the griseusin B framework via a one-pot annulation-methylation
      double deprotection-spirocyclization sequence.
AB  - A highly convergent synthesis of the griseusin B scaffold is described. The key
      step involves an efficient one-pot Hauser-Kraus annulation-methylation-double
      deprotection-spirocyclization sequence that directly affords the target parent
      tetracyclic ring system.

PMID- 23560612
TI  - Poor sleep quality impairs cognitive performance in older adults.
AB  - The prevalence of insomnia increases with age. Short sleep duration is associated
      with deficits in cognitive performance. We hypothesized that short sleep duration
      and sleep quality influence cognitive performance in older adults. The study
      included 78 adults aged 60 years and over (72.2 +/- 5.9 years). Total sleep time
      and sleep efficiency (total sleep time/time in bed * 100) were calculated using
      actigraphy. We evaluated cognitive performance with the continuous performance
      test-identical pairs and the number-back test. Sleep apnea was evaluated
      overnight with a portable home monitoring system. The accuracy of the 0-back test
      significantly decreased in participants with total sleep time less than 5 h
      compared with those with total sleep time greater than 7 h, but there was no
      significant difference in continuous performance test-identical pairs between the
      two groups. Participants with sleep efficiency <85% showed a significant decrease
      in 0- and 1-back test accuracy compared with those with sleep efficiency >=85%.
      There were no significant differences in the accuracy of number-back tests and
      continuous performance test-identical pairs between apnea-hypopnea index >=15 h(
      1) and apnea-hypopnea index <15 h(-1) groups, or among lowest SpO2  >= 90%,
      lowest 80-90%, and lowest SpO2  < 80% groups. Age, total sleep time and sleep
      efficiency were significantly correlated with accuracy on the 0-back test. Age
      and sleep efficiency were significantly correlated with accuracy on the 1-back
      test. Multiple regression analysis revealed that total sleep time was
      independently correlated with accuracy on the 0-back test, while age was
      independently correlated with accuracy on the 1-back test. Our findings suggest
      that sleep duration and sleep quality may play a role in cognitive performance in
      older adults. 

PMID- 23560614
TI  - Constructing a model: economic evaluations in transfusion medicine, Part 3.

PMID- 23560613
TI  - Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese
      population.
AB  - BACKGROUND: The expression of MU-opioid receptor has important role in cognitive
      dysfunction in Schizophrenia (SZ). The results of studies about the association
      of polymorphisms of MU-opioid receptor gene (OPRM1) with SZ were inconsistent.
      METHODS: We conducted a case-control study to investigate the genetic association
      between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ
      patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1
      were successfully genotyped by using PCR-RFLP. RESULTS: Of four polymorphisms,
      rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A
      allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and
      rs2075572 was associated with an almost 0.46-fold risk (OR=0.46, 95% CI: 0.357
      0.59, P<0.01) and 0.7-fold risk (OR=0.707, 95% CI: 0.534-0.937, P=0.015) of the
      occurrence of SZ,. When subjects were divided by gender, rs1799971 remained
      significant difference only in males (OR=0.309, 95% CI: 0.218-0.439 for G allele,
      P<0.01), and rs2075572 only in females (OR=0.399, 95% CI: 0.246-0.648 for G
      allele, P<0.01). In secondary analysis with subsets of patients, the G allele of
      rs1799971 (compared to the A allele) was associated with a decreased risk of all
      patients and male patients with apathy symptoms (OR=0.086, 95% CI: 0.048-0.151,
      P=0.01; OR=0.083, 95% CI: 0.045-0.153, P<0.01), and the G allele of rs2075572
      (compared to the C allele) was associated with a decreased risk of all patients
      and female patients with positive family history (OR=0.468, 95% CI: 0.309-0.71,
      P<0.01; OR=0.34, 95% CI: 0.195-0.593, P<0.01). In addition, haplotype analysis
      revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with
      decreased risks of SZ (P<0.01). The other two (G-C-C-G and G-G-C-G) with
      increased risks of SZ (P<0.01). CONCLUSIONS: The present study demonstrated for
      the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia
      in the Han Chinese. Further studies are needed to give a global view of this
      polymorphism in pathogenesis of schizophrenia in a large-scale sample, family
      based association design or well-defined subgroups of schizophrenia.

PMID- 23560615
TI  - Trichuris spp. (Nematoda: Trichuridae) from two rodents, Mastomys natalensis and
      Gerbilliscus vicinus in Tanzania.
AB  - During a survey of the helminth community of several rodent species in the
      Morogoro region (Tanzania), Trichuris whipworms (Nematoda: Trichuridae) were
      found in the ceca of the Natal multimammate mouse, Mastomys natalensis and a
      gerbil, Gerbilliscus vicinus (both Rodentia: Muridae). The taxonomic literature
      regarding Trichuris from African native rodents describes 10 species, but
      includes few metric and morphologic characters that discriminate between some of
      the pairs. The whipworms we sampled in Tanzanian Natal multimammate mice and
      gerbils were morphologically identified, respectively, as Trichuris mastomysi
      Verster, 1960 and Trichuris carlieri Gedoelst, 1916 sensu lato, but with
      characters that overlap or partially overlap with the cosmopolitan Murinae
      whipworm, Trichuris muris , already reported from several rodents in Africa. To
      clarify our identification, we sequenced the ITS-1, 5.8S, and ITS-2 ribosomal DNA
      region of the worms' nuclear genome. The genetic analyses clearly distinguish the
      whipworms we found in M. natalensis from those found in the gerbil, and both of
      these from T. muris whipworm reference sequences. The overlap of morphological
      characters between rodent whipworms suggests that reports of T. muris from rodent
      species not closely related to Murinae in other parts of Africa should be treated
      with caution.

PMID- 23560616
TI  - An evaluation of the latest evidence relating to renin-angiotensin system
      inhibitors.
AB  - INTRODUCTION: In the last few years, a number of important clinical trials have
      been completed that have investigated the inhibition of the renin-angiotensin
      system. New drugs, focusing on this system, have now emerged as a result. AREAS
      COVERED: The authors review the most relevant information available, reported
      from the last 5 years, pertaining to the most important clinical trials on renin
      angiotensin system blockers (ARBs). The authors' data review includes the trials
      of aliskiren, telmisartan, olmesartan and azilsartan. The authors also review the
      possible risk of cancer with ARBs. EXPERT OPINION: The results of ASPIRE and
      ALTITUDE trials strongly suggested that dual inhibition of aliskiren with either
      ARBS or angiotensin converting enzyme inhibitors (ACEi) should be avoided.
      Olmesartan is an effective and safe antihypertensive agent, but special attention
      should be paid to high-risk patients, such as those with coronary disease, to
      avoid an excessive reduction in blood pressure. The authors also note that while
      azilsartan is probably the most potent ARB, there is still a lack of data
      regarding potential organ damage and the incidence of cardiovascular events.
      Lastly, recent evidence has shown a lack of a relationship between ARB therapy
      and the occurrence of cancer.

PMID- 23560617
TI  - Molecular strategies to prevent, inhibit, and degrade advanced glycoxidation and
      advanced lipoxidation end products.
AB  - The advanced glycoxidation end products (AGEs) and lipoxidation end products
      (ALEs) contribute to the development of diabetic complications and of other
      pathologies. The review discusses the possibilities of counteracting the
      formation and stimulating the degradation of these species by pharmaceuticals and
      natural compounds. The review discusses inhibitors of ALE and AGE formation,
      cross-link breakers, ALE/AGE elimination by enzymes and proteolytic systems,
      receptors for advanced glycation end products (RAGEs) and blockade of the ligand
      RAGE axis.

PMID- 23560618
TI  - Exhaled nitric oxide indicates poorly athlete's asthma.
AB  - INTRODUCTION: In athletes, exercise-induced respiratory symptoms are common and
      their assessment is time and resource consuming. OBJECTIVE: The objective was to
      evaluate fractional concentration of exhaled nitric oxide (FENO) as a predictor
      of bronchial hyperresponsiveness (BHR) and of asthma. MATERIALS AND METHODS:
      Eighty-seven elite athletes and a control group of 87 sedentary patients with
      symptoms suggesting asthma underwent measurements of FENO and of BHR by using
      methacholine provocation test (MCH) and eucapnic voluntary hyperpnoea (EVH)
      (athletes) or histamine provocation test (HIST) (controls). RESULTS: In athletes,
      elevated FENO (>30 ppb) was not associated with lung function-confirmed asthma or
      with MCH positivity, but receiver operating characteristics (ROC) analysis showed
      some predictive value for EVH positivity [Area Under Curve (AUC) 0.652, 95%
      confidence interval (CI): 0.53 to 0.78, P = 0.020]. However, the sensitivity
      (55%) and the specificity (71%) were poor. In sedentary patients, FENO was
      significantly associated with both confirmed asthma and HIST positivity, ROC
      analysis showing FENO to be significantly predictive for HIST positivity (AUC
      0.83, 95% CI: 0.70 to 0.96, P = 0.001) and for asthma (AUC 0.74, 95% CI: 0.63 to
      0.85, P < 0.001). CONCLUSION: The results suggest that in contrast to sedentary
      patients, FENO seems to be a poor predictor of BHR and of clinical asthma in
      elite athletes. We find it unlikely that FENO could be a useful screening tool in
      athletes with exercise-induced respiratory symptoms.

PMID- 23560619
TI  - Risk factors for early re-bleeding and associated hospitalization in patients
      with colonic diverticular bleeding.
AB  - AIM: The annual incidence of colonic diverticular bleeding is increasing, but
      treatments are not yet well established. Here we aimed to identify the risk
      factors for early re-bleeding and to determine the associated duration of
      hospitalization. METHOD: Records of 90 emergent patients with colonic
      diverticular bleeding between 1999 and May 2012 were retrospectively reviewed.
      They were divided into an early re-bleeding within 1 month group (n = 24) and a
      no re-bleeding group (n = 66) and we investigated the risk factors for early re
      bleeding. In the former group, we calculated the time from the first haemostasis
      to early re-bleeding and the associated duration of hospitalization. RESULTS:
      Univariate analysis showed that there were significantly more patients with signs
      of shock (P = 0.00055) and active bleeding on the first colonoscopy after
      admission (P = 0.020) in the early re-bleeding group. Multivariate conditional
      logistic regression analysis using stepwise variable selection showed that signs
      of shock on admission (odds ratio, 5.23; 95% confidence interval, 1.84-14.90; P =
      0.0019) remained statistically significant. All patients who re-bled without
      signs of shock (n = 7) and 16 of 17 with signs of shock re-bled within 126 h
      (5.25 days) of initial hospitalization. CONCLUSION: Shock was an independent risk
      factor for early re-bleeding. The associated duration of hospitalization was 6
      days.

PMID- 23560621
TI  - What factors control O2 binding and release thermodynamics in mononuclear
      ruthenium water oxidation catalysts? A theoretical exploration.
AB  - Mononuclear Ru-based water oxidation catalysts (WOCs) constitute an important
      class of WOCs for water splitting. This work constitutes a systematic study of Ru
      O2 complexes of mononuclear ruthenium WOCs, with a focus on the thermodynamics of
      water-assisted O2 release in various electronic states and conformations. Our
      extensive DFT study reveals several factors that affect the O2 release
      thermodynamics: (1) steric effect from the ligand sphere of Ru; (2) trans effect
      of ligands trans to O2; (3) oxygen cis coordinating effect; (4) carbon
      coordinating effect; and (5) Ru coordination strength. Some of these effects
      could selectively stabilize/destabilize some states/conformations of the Ru-O2
      complexes relative to Ru-OH2 complexes, and affect thereby the O2 release
      thermodynamics. The identification and rationalization of factors for O2 release
      thermodynamics, as in this work, could be helpful toward a better understanding
      of this final step of the ruthenium-catalyzed water oxidation.

PMID- 23560620
TI  - One-year outcomes of unipolar depression patients with manic or hypomanic switch
      during acute antidepressant treatment.
AB  - OBJECTIVE: The aim of the study was to investigate one-year outcomes of unipolar
      depression patients with manic or hypomanic switch during acute antidepressant
      treatment. METHODS: A review of medical records revealed 37 consecutive patients
      admitted from 1997 to 2002 who underwent an antidepressant-induced manic or
      hypomanic switch fulfilling DSM-IV criteria. Their clinical courses were
      retrospectively investigated after discharge. RESULTS: Of the 37 patients, 33
      (89.2%) were followed up for 1 year after discharge. None developed a manic
      episode, while seven developed a hypomanic episode, including 1 patient who was
      lost after emerging from a hypomanic episode within 6 months after discharge.
      Only one of those seven patients developed hypomania during acute antidepressant
      treatment for a recurrent depressive episode under maintenance mood stabilizer
      treatment. Furthermore, bipolar conversion occurred in four patients within the
      first 6 months and in another two patients, including 1 with rapid cycling, over
      the subsequent 6 months after discharge. Of these 33 patients, 28 received
      continuous maintenance treatment with mood stabilizers for the one-year period
      after discharge. CONCLUSIONS: The subjects were considered to have a bipolar
      nature according to the prevalence rate of bipolar conversion over a one-year
      period. Longer follow-up studies appear warranted determine the diagnostic issues
      of antidepressant-induced switch in unipolar depression.

PMID- 23560622
TI  - Deciphering the aetiology of a mixed fungal infection by broad-range PCR with
      sequencing and fluorescence in situ hybridisation.
AB  - Simultaneous infections with multiple fungi may be misinterpreted as
      monomicrobial infections by current diagnostics with ramifications for the choice
      of antimicrobial agents that may impact patient outcomes. The application of
      molecular methods on tissue samples may be useful to decipher the aetiology of
      mixed fungal infections. We present a leukaemic patient who died from sepsis due
      to candidaemia. The postmortem examination documented fungal elements in lung
      tissue. Fungal DNA was amplified from the lung sample by broad-range PCR assays
      targeting the 28S ribosomal RNA gene or the internal transcribed spacer 2 (ITS
      2). Fluorescence in situ hybridisation (FISH) using differentially labelled
      fungal probes was applied on the tissue. Sequencing identified the PCR amplicons
      as Aspergillus fumigatus (28S assay) and Candida tropicalis (ITS-2 assay). As a
      chromatogram suggested mixed amplicons, the Isentio ripseq((r)) tool for in
      silico analysis was applied and confirmed the presence of both amplicons in the
      PCR products of both assays. FISH confirmed the presence of Aspergillus and
      Candida within the infectious process, a prerequisite for inferring a causal
      relationship with the infection. The combination of broad-range PCR with sequence
      analysis and FISH applied on tissue samples is a powerful approach to identify
      the aetiology of invasive fungal infections, including mixed infections. 

PMID- 23560623
TI  - Summer community structure of aerobic anoxygenic phototrophic bacteria in the
      western Arctic Ocean.
AB  - Aerobic anoxygenic phototrophic (AAP) bacteria are found in a range of aquatic
      and terrestrial environments, potentially playing unique roles in biogeochemical
      cycles. Although known to occur in the Arctic Ocean, their ecology and the
      factors that govern their community structure and distribution in this extreme
      environment are poorly understood. Here, we examined summer AAP abundance and
      diversity in the North East Pacific and the Arctic Ocean with emphasis on the
      southern Beaufort Sea. AAP bacteria comprised up to 10 and 14% of the prokaryotic
      community in the bottom nepheloid layer and surface waters of the Mackenzie
      plume, respectively. However, relative AAP abundances were low in offshore
      waters. Environmental pufM clone libraries revealed that AAP bacteria in the
      Alphaproteobacteria and Betaproteobacteria classes dominated in offshore and in
      river-influenced surface waters, respectively. The most frequent AAP group was a
      new uncultivated betaproteobacterial clade whose abundance decreased along the
      salinity gradient of the Mackenzie plume even though its photosynthetic genes
      were actively expressed in offshore waters. Our data indicate that AAP bacterial
      assemblages represented a mixture of freshwater and marine taxa mostly restricted
      to the Arctic Ocean and highlight the substantial influence of riverine inputs on
      their distribution in coastal environments. 

PMID- 23560624
TI  - Is there a link between amyotrophic lateral sclerosis and treatment with TNF
      alpha inhibitors?

PMID- 23560625
TI  - Magnitude and origin of the enhanced basicity of the catalytic glutamate of
      triosephosphate isomerase.
AB  - Glu-167 of triosephosphate isomerase from Trypanosoma brucei brucei (TbbTIM) acts
      as the base to deprotonate substrate to form an enediolate phosphate trianion
      intermediate. We report that there is a large ~6 pK unit increase in the basicity
      of the carboxylate side chain of Glu-167 upon binding of the inhibitor
      phosphoglycolate trianion (I(3-)), an analog of the enediolate phosphate
      intermediate, from pKEH ~ 4 for the protonated free enzyme EH to pK(EHI) ~ 10 for
      the protonated enzyme-inhibitor complex EH*I(3-). We propose that there is a
      similar increase in the basicity of this side chain when the physiological
      substrates are deprotonated by TbbTIM to form an enediolate phosphate trianion
      intermediate and that it makes an important contribution to the enzymatic rate
      acceleration. The affinity of wildtype TbbTIM for I(3-) increases 20,000-fold
      upon decreasing the pH from 9.3 to 4.9, because TbbTIM exists mainly in the basic
      form E over this pH range, while the inhibitor binds specifically to the rare
      protonated enzyme EH. This reflects the large increase in the basicity of the
      carboxylate side chain of Glu-167 upon binding of I(3-) to EH to give EH*I(3-).
      The I172A mutation at TbbTIM results in an ~100-fold decrease in the affinity of
      TbbTIM for I(3-) at pH < 6 and an ~2 pK unit decrease in the basicity of the
      carboxylate side chain of Glu-167 at the EH*I(3-) complex, to pK(EHI) = 7.7.
      Therefore, the hydrophobic side chain of Ile-172 plays a critical role in
      effecting the large increase in the basicity of the catalytic base upon the
      binding of substrate and/or inhibitors.

PMID- 23560626
TI  - GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with
      CEBPA mutations.
AB  - GATA2 mutations have recently been reported in acute myeloid leukaemia (AML)
      patients with CEBPA-double mutations. To explore their impact on this favourable
      risk disease, we determined GATA2 status in 153 sporadic AML patients and three
      members of a germ-line CEBPA-mutant family at AML presentation. Overall, 27%
      (15/55) CEBPA-double, 16% (7/43) CEBPA-single and 0% (0/55) normal
      karyotype/CEBPA-wild-type patients were GATA2-mutant. All familial AML patients
      acquired both a second CEBPA and a GATA2 mutation. CEBPA and GATA2 mutant levels
      indicated that both mutations were likely to be early events in leukaemogenesis.
      GATA2 status did not impact on the favourable outcome of CEBPA-double/FLT3
      inernal tandem duplication-negative patients.

PMID- 23560627
TI  - Biological dosimetry by automated dicentric scoring in a simulated emergency.
AB  - Dicentric chromosome analysis remains the most widely used method in
      biodosimetry. It has a lower detection limit of about 0.1 Gy, and allows one to
      distinguish between whole- and partial-body exposures. A drawback of the
      dicentric analysis is that it is a time consuming method and maybe difficult to
      implement in a mass casualty event. To try to increase the analysis capacity,
      automatic dicentric scoring (ADS) using image analysis software is being
      incorporated in several laboratories. Here we present the results obtained in an
      emergency exercise simulating 50 victims. The ability to distinguish different
      radiations scenarios is evaluated. To simulate whole-body exposures peripheral
      blood samples were irradiated at doses between 0-4.7 Gy, and to simulate partial
      body exposures irradiated and nonirradiated blood were mixed in different
      proportions. With the data obtained from the first slide analyzed (with about 300
      400 cells), 32 of 34 simulated whole-body exposures were correctly classified
      according to radiation exposure levels. For simulated partial-body irradiations,
      it was possible to detect them as partial exposures at the end of the first slide
      analyzed but only at the highest doses. In all cases the classification was
      updated every time the analysis of one additional slide was finished. The
      comparison between our present results and those reported in the literature for
      manual scoring shows that for triage purposes the ADS based on 300-400 cells is
      similar in efficiency to classifying the cases based on manual scoring of 50
      cells. However, if one accounts for the associated uncertainties and the time
      needed for ADS, we suggest that ADS triage scoring should be based on about 1,000
      cells. For final dose estimations the number of cells to score will depend on the
      initial estimated dose, and on the information contributed from physical dose
      reconstruction or clinical symptoms. At doses higher than 1 Gy, we propose
      analysis of 1,500 and for lower doses or suspected partial-body exposures, the
      number of cells to score should be 3,000.

PMID- 23560628
TI  - A mechanistic model for medulloblastoma induction in mice.
AB  - Medulloblastomas in Patched heterozygous mice (Ptc1(+/-) mice) are induced with
      high probability by ionizing radiation applied in the immediate post-natal
      period. A mathematical model is described here that accommodates the dependence
      of the medulloblastoma incidence on dose, age at exposure and age. The model
      assumes that the first step in the development of the cancer is already present
      in all cells of the patched mouse due to germ-line inactivation of one allele of
      the patched tumor suppressor gene. The subsequent rate-limiting step is dependent
      linearly on dose at least up to 3 Gy. The observed strong decrease in
      carcinogenic effect of radiation between exposure on day 1 and day 10 is
      described by a physiological elimination of target cells during post-natal
      maturation of the brain. A single malignant cell develops into a tumor following
      a gamma-distribution with mean of about 160 days. The multiplicity of
      medulloblastomas is predicted.

PMID- 23560629
TI  - Selective inhibition of microglia-mediated neuroinflammation mitigates radiation
      induced cognitive impairment.
AB  - Cognitive impairment precipitated by irradiation of normal brain tissue is
      commonly associated with radiation therapy for treatment of brain cancer, and
      typically manifests more than 6 months after radiation exposure. The risks of
      cognitive impairment are of particular concern for an increasing number of long
      term cancer survivors. There is presently no effective means of preventing or
      mitigating this debilitating condition. Neuroinflammation mediated by activated
      microglial cytokines has been implicated in the pathogenesis of radiation-induced
      cognitive impairment in animal models, including the disruption of neurogenesis
      and activity-induced gene expression in the hippocampus. These pathologies evolve
      rapidly and are associated with relatively subtle cognitive impairment at 2
      months postirradiation. However, recent reports suggest that more profound
      cognitive impairment develops at later post-irradiation time points, perhaps
      reflecting a gradual loss of responsiveness within the hippocampus by the
      disruption of neurogenesis. We hypothesized that inhibiting neuroinflammation
      using MW01-2-151SRM (MW-151), a selective inhibitor of proinflammatory cytokine
      production, might mitigate these deleterious radiation effects by
      preserving/restoring hippocampal neurogenesis. MW-151 therapy was initiated 24 h
      after 10 Gy whole-brain irradiation (WBI) administered as a single fraction and
      maintained for 28 days thereafter. Proinflammatory activated microglia in the
      dentate gyrus were assayed at 2 and 9 months post-WBI. Cell proliferation and
      neurogenesis in the dentate gyrus were assayed at 2 months post-WBI, whereas
      novel object recognition and long-term potentiation were assayed at 6 and 9
      months post-WBI, respectively. MW-151 mitigated radiation-induced
      neuroinflammation at both early and late time points post-WBI, selectively
      mitigated the deleterious effects of irradiation on hippocampal neurogenesis, and
      potently mitigated radiation-induced deficits of novel object recognition
      consolidation and of long-term potentiation induction and maintenance. Our
      results suggest that transient administration of MW-151 is sufficient to
      partially preserve/restore neurogenesis within the subgranular zone and to
      maintain the functional integrity of the dentate gyrus long after MW-151 therapy
      withdrawal.

PMID- 23560631
TI  - The non-homologous end-joining (NHEJ) mathematical model for the repair of double
      strand breaks: II. Application to damage induced by ultrasoft X rays and low
      energy electrons.
AB  - We investigated the kinetics of simple and complex types of double-strand breaks
      (DSB) using our newly proposed mechanistic mathematical model for NHEJ DSB
      repair. For this purpose the simulated initial spectrum of DNA DSB, induced in an
      atomistic canonical model of B-DNA by low-energy single electron tracks, 100 eV
      to 4.55 keV, and the electrons generated by ultrasoft X rays (CK, AlK and TiK),
      were subjected to NHEJ repair processes. The activity elapsed time of
      sequentially independent steps of repair performed by proteins involved in NHEJ
      repair process were calculated for separate DSB. The repair kinetics of DSBs were
      computed and compared with published data on repair kinetics obtained by pulsed
      field gel electrophoresis method. The comparison shows good agreement for V79-4
      cells irradiated with ultrasoft X rays. The average times for the repair of
      simple and complex DSB confirm that double-strand break complexity is a potential
      explanation for the slow component of DSB repair observed in V79-4 cells
      irradiated by ultrasoft X rays.

PMID- 23560630
TI  - Autosomal mutations in mouse kidney epithelial cells exposed to high-energy
      protons in vivo or in culture.
AB  - Proton exposure induces mutations and cancer, which are presumably linked.
      Because protons are abundant in the space environment and significant
      uncertainties exist for the effects of space travel on human health, the purpose
      of this study was to identify the types of mutations induced by exposure of
      mammalian cells to 4-5 Gy of 1 GeV protons. We used an assay that selects for
      mutations affecting the chromosome 8-encoded Aprt locus in mouse kidney cells and
      selected mutants after proton exposure both in vivo and in cell culture. A loss
      of heterozygosity (LOH) assay for DNA preparations from the in vivo-derived
      kidney mutants revealed that protons readily induced large mutational events.
      Fluorescent in situ hybridization painting for chromosome 8 showed that >70% of
      proton-induced LOH patterns resembling mitotic recombination were in fact the
      result of nonreciprocal chromosome translocations, thereby demonstrating an
      important role for DNA double-strand breaks in proton mutagenesis. Large
      interstitial deletions, which also require the formation and resolution of double
      strand breaks, were significantly induced in the cell culture environment (14% of
      all mutants), but to a lesser extend in vivo (2% of all mutants) suggesting that
      the resolution of proton-induced double-strand breaks can differ between the
      intact tissue and cell culture microenvironments. In total, the results
      demonstrate that double-strand break formation is a primary determinant for
      proton mutagenesis in epithelial cell types and suggest that resultant LOH for
      significant genomic regions play a critical role in proton-induced cancers.

PMID- 23560632
TI  - Thyroid dose estimates for a cohort of Belarusian children exposed to radiation
      from the Chernobyl accident.
AB  - The U.S. National Cancer Institute, in collaboration with the Belarusian Ministry
      of Health, is conducting a study of thyroid cancer and other thyroid diseases in
      a cohort of about 12,000 persons who were exposed to fallout from the Chernobyl
      accident in April 1986. The study subjects were 18 years old or younger at the
      time of exposure and resided in Belarus in the most contaminated areas of the
      Gomel and Mogilev Oblasts, as well as in the city of Minsk. All cohort members
      had at least one direct thyroid measurement made in April-June 1986. Individual
      data on residential history, consumption of milk, milk products and leafy
      vegetables as well as administration of stable iodine were collected for all
      cohort members by means of personal interviews conducted between 1996 and 2007.
      Based on the estimated (131)I activities in the thyroids, which were derived from
      the direct thyroid measurements, and on the responses to the questionnaires,
      individual thyroid doses from intakes of (131)I were reconstructed for all cohort
      members. In addition, radiation doses to the thyroid were estimated for the
      following minor exposure pathways: (a) intake of short-lived (132)I, (133)I and
      (132)Te by inhalation and ingestion; (b) external irradiation from radionuclides
      deposited on the ground; and (c) ingestion intake of (134)Cs and (137)Cs. Intake
      of (131)I was the major pathway for thyroid exposure; its mean contribution to
      the thyroid dose was 92%. The thyroid doses from (131)I intakes varied from 0.5
      mGy to almost 33 Gy; the mean was estimated to be 0.58 Gy, while the median was
      0.23 Gy. The reconstructed doses are being used to evaluate the risk of thyroid
      cancer and other thyroid diseases in the cohort.

PMID- 23560633
TI  - Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate
      ovalbumin-induced allergic asthma in mice.
AB  - Gamma radiation is used for several therapeutic indications such as cancers and
      autoimmune diseases. Low-dose whole-body gamma irradiation has been shown to
      activate immune responses in several ways, however, the effect and mechanism of
      irradiation on allergic asthma remains poorly understood. This study investigated
      whether or not irradiation exacerbates allergic asthma responses and its
      potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin
      (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3
      consecutive days with a dose of 0.667 Gy using (137)Cs gamma rays 24 h before
      every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE
      levels, the number of inflammatory cells including mast cells, goblet cell
      hyperplasia, collagen deposition, airway hyperresponsiveness, expression of
      inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-kappaB)
      and activator protein-1 activities. All of these factors were increased in BAL
      cells and lung tissue of OVA-challenged mice. Irradiation increased the number of
      Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and
      lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF
      kappaB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing
      OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells
      (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-beta were decreased.
      The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg
      cells, which reduce OVA-induced allergic airway inflammation and tissue
      remodeling through the down-regulation of migration by the CCL2/CCR2 axis and
      activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice.

PMID- 23560634
TI  - Comparative analysis of cell killing and autosomal mutation in mouse kidney
      epithelium exposed to 1 GeV protons in vitro or in vivo.
AB  - Human exposure to high-energy protons occurs in space flight scenarios or, where
      necessary, during radiotherapy for cancer or benign conditions. However, few
      studies have assessed the mutagenic effectiveness of high-energy protons, which
      may contribute to cancer risk. Mutations cause cancer and most cancer-associated
      mutations occur at autosomal loci. This study addresses the cytotoxic and
      mutagenic effects of 1 GeV protons in mouse kidney epithelium. Mutant fractions
      were measured for an endogenous autosomal locus (Aprt) that detects all types of
      mutagenic events. Results for kidneys irradiated in vivo are compared with the
      results for kidney cells from the same strain exposed in vitro. The results
      demonstrate dose-dependent cell killing in vitro and for cells explanted 3-4
      months postirradiation in vivo. Incubation in vivo for longer periods (8-9
      months) further attenuates proton-induced cell killing. Protons are mutagenic to
      cells in vitro and for in vivo irradiated kidneys. The dose-response for Aprt
      mutation is curvilinear after in vitro or in vivo exposure, bending upward at the
      higher doses. While the absolute mutant fractions are higher in vivo, the fold
      increase over background is similar for both in vitro and in situ exposures.
      Results are also presented for a limited study on the effect of dose
      fractionation on the induction of Aprt mutations in kidney epithelial cells. Dose
      fractionation reduces the fraction of proton-induced Aprt mutants in vitro and in
      vivo and also results in less cell killing. Taken together, the mutation burden
      in the epithelium is slightly reduced by dose-fractionation. Autosomal mutations
      accumulated during clinical exposure to high-energy protons may contribute to the
      risk of treatment-associated neoplasms, thereby highlighting the need for
      rigorous treatment planning to reduce the dose to normal tissues. For low dose
      exposures that occur during most space flight scenarios, the mutagenic effects of
      protons appear to be modest.

PMID- 23560635
TI  - The non-homologous end-joining (NHEJ) pathway for the repair of DNA double-strand
      breaks: I. A mathematical model.
AB  - This article presents a biochemical kinetic model for the non-homologous end
      joining (NHEJ) of DNA double-strand break (DSB) repair pathway. The model is part
      of a theoretical framework to encompass all cellular DSB repair pathways. The
      NHEJ model was developed by taking into consideration the biological
      characteristics of the repair processes in the absence of homologous
      recombination (HR), the major alternative pathway for DSB repair. The model
      considers fast and slow components of the repair kinetics resulting in a set of
      differential equations that were solved numerically. In the absence of available
      published data for reaction rate constants for the repair proteins involved in
      NHEJ, we propose reaction rate constants for the solution of the equations. We
      assume as a first approximation that the reaction rate constants are applicable
      to mammalian cells under same conditions. The model was tested by comparing
      measured and simulated DSB repair kinetics obtained with HR-deficient cell lines
      irradiated by X rays in the dose range of 20-80 Gy. Measured data for initial
      protein recruitment to a DSB were used to independently estimate rate constants
      for Ku70/Ku80 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We
      show here based on the model of DSB repair described in this article, application
      of the model in the accompanying article (Taleei et al., Radiat. Res. 179, 540
      548, 2013) and by simulation of repair times for each individual DSB produced by
      individual tracks of electrons, that the complexity of damage may explain the
      slow kinetics of DNA DSB repair.

PMID- 23560636
TI  - Issues in low dose radiation biology: the controversy continues. A perspective.
AB  - Both natural and man-made sources of ionizing radiation contribute to human
      exposure and consequently pose a possible risk to human health. Much of this is
      unavoidable, e.g., natural background radiation, but as the use of radiation
      increases, so does the potential health risk and the public's concerns. This
      perspective reflects the authors' view of current issues in low dose radiation
      biology research, highlights some of the controversies therein, and suggests
      areas of future research to address both issues in low dose radiation research
      and the controversies. This is a critical time for the radiation sciences and the
      implications of future research will have a significant impact on radiation
      protection, medicine, national security, research and industry. The views
      expressed here are the authors' own and do not represent any institution,
      organization or funding body.

PMID- 23560637
TI  - International symposium on challenges in chemical biology: toward the formation
      of Chemical Biology Society of India.

PMID- 23560638
TI  - The orphan protein bis-gamma-glutamylcystine reductase joins the pyridine
      nucleotide disulfide reductase family.
AB  - Facile DNA sequencing became possible decades after many enzymes had been
      purified and characterized. Consequently, there are still "orphan" enyzmes for
      which activities are known but for which encoding genes have not been identified.
      Identification of the genes encoding orphan enzymes is important because it
      allows correct annotation of genes of unknown function or with misassigned
      function. Bis-gamma-glutamylcystine reductase (GCR) is an orphan protein that was
      purified in 1988. This enzyme catalyzes the reduction of bis-gamma
      glutamylcystine. gamma-Glutamylcysteine is the major low-molecular weight thiol
      in halobacteria. We purified GCR from Halobacterium sp. NRC-1 and identified the
      sequence of 23 tryptic peptides by nano-liquid chromatography electrospray
      ionization tandem mass spectrometry. These peptides cover 62% of the protein
      predicted to be encoded by a gene in Halobacterium sp. NRC-1 that is annotated as
      mercuric reductase. GCR and mercuric reductase activities were assayed using
      enzyme that was expressed in Escherichia coli and refolded from inclusion bodies.
      The enzyme had robust GCR activity but no mercuric reductase activity. The
      genomes of most, but not all, halobacteria for which whole genome sequences are
      available have close homologues of GCR, suggesting that there is more to be
      learned about the low-molecular weight thiols used in halobacteria.

PMID- 23560639
TI  - Patient-reported outcomes of 182 adults with severe haemophilia in Germany
      comparing prophylactic vs. on-demand replacement therapy.
AB  - Clotting factor replacement therapy has a major impact on the quality of life in
      patients with haemophilia. To analyse and compare the outcomes of on-demand and
      prophylactic treatment regimens in child- and adulthood, a self-evaluation
      questionnaire was sent to 182 patients over 30 years of age with severe
      haemophilia A or B. Analysis of the questionnaire results revealed that most
      study participants had been treated on-demand in childhood, but that the majority
      of these patients subsequently switched to prophylaxis. However, of those
      patients who began with prophylaxis as children, the vast majority maintained
      prophylactic treatment as adults. Inhibitor development was reported
      significantly more frequently by patients who started with on-demand treatment
      than by those who started with prophylaxis. In the year prior to completing the
      questionnaire, adults with severe haemophilia who received prophylactic treatment
      reported a significantly lower incidence of bleeding as a result of more frequent
      factor consumption. These results are in close accordance with published
      prospective data. Although nearly all patients with severe haemophilia had joint
      pain due to bleeding, those who had always had prophylactic treatment reported
      superior outcomes in terms of the need for joint replacement, walking speed and
      distance, participation in school sports and further education. These data
      clearly underline the superiority of prophylactic treatment for the majority of
      individuals with severe haemophilia. The worst outcomes were found in those
      treated on-demand in childhood who later switched to prophylaxis. In contrast to
      most studies which have compared treatment regimens on the basis of data from
      healthcare professionals, this study reflects treatment outcomes from the
      patient's perspective.

PMID- 23560640
TI  - Establishing a framework: economic evaluations in transfusion medicine, part 2.

PMID- 23560641
TI  - Reply to Couch et al.

PMID- 23560642
TI  - Highly practical synthesis of nitriles and heterocycles from alcohols under mild
      conditions by aerobic double dehydrogenative catalysis.
AB  - A mild, aerobic, catalytic process for obtaining nitriles directly from alcohols
      and aqueous ammonia is described. The reaction proceeds via a dehydrogenation
      cascade mediated by catalytic CuI, bpy, and TEMPO in the presence of O2. The
      substrate scope is broad including various functionalized aromatic and aliphatic
      alcohols. This protocol enabled the one-pot synthesis of various biaryl
      heterocycles directly from commercially available alcohols.

PMID- 23560643
TI  - A localized surface plasmon resonance imaging instrument for multiplexed
      biosensing.
AB  - Localized surface plasmon resonance (LSPR) spectroscopy has been widely used for
      label-free, highly sensitive measurements of interactions at a surface. LSPR
      imaging (LSPRi) has the full advantages of LSPR but enables high-throughput,
      multiplexed measurements by simultaneously probing multiple individually
      addressable sensors on a single sample surface. Each spatially distinct sensor
      can be tailored to provide data regarding different surface functionalities or
      reaction environments. Previously, LSPRi has focused on single-particle sensing
      where the size scale is very small. Here, we create defined macroscale arrays of
      nanoparticles that are compatible with common patterning methods such as dip-pen
      nanolithography and multichannel microfluidic delivery devices. With this new
      LSPR sensing format, we report the first demonstration of multiplexed LSPR
      imaging and show that the increased throughput of our instrument enables the
      collection of a complete Langmuir binding curve on a single sensor surface. In
      addition, the multiplexed LSPR sensor is highly selective, as demonstrated by the
      hybridization of single-stranded DNA to complementary sequences immobilized on
      the sensor surface. The LSPR arrays described in this work exhibit uniform
      sensitivity and tailorable optical properties, making them an ideal platform for
      high-throughput, label-free analysis of a variety of molecular binding
      interactions. 

PMID- 23560644
TI  - Polymorphisms in genes involved in the free-radical process in patients with
      sudden sensorineural hearing loss and Meniere's disease.
AB  - The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and
      Meniere's disease remain unclear. Recently, accumulating evidence has
      demonstrated that free radicals are related to the pathology of inner ear
      disease. Because genetic factors may contribute partly to the etiologies of SSNHL
      and Meniere's disease, we investigated the association between genetic
      polymorphisms located in genes related to the free-radical process and
      susceptibility to SSNHL and Meniere's disease. We compared 83 patients affected
      by SSNHL and 83 patients affected by Meniere's disease with 2048 adults (for
      SSNHL) and 1946 adults (for Meniere's disease) who participated in the National
      Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic
      regression was used to calculate odds ratios (ORs) for SSNHL and Meniere's
      disease in individuals with polymorphisms in the genes: methionine synthase (MTR;
      rs1805087); methionine-synthase reductase (MTRR; rs1801394); nitric oxide
      synthase 3 (NOS3; rs1799983); caveolin 1 (Cav1; rs3840634); melatonin receptor 1B
      (MTNR1B; rs1387153); NAD(P)H oxidase p22(phox) subunit (NADH/NADPHp22phox;
      rs4673); and mitochondria 5178 (MT5178; rs28357984). The NOS3 polymorphism was
      significantly associated with a risk of SSNHL; in addition, the OR for the NOS3
      polymorphism and SSNHL risk was 2.108 (CI, 1.343-3.309) with adjustment for age
      and sex. The Cav1 polymorphism was significantly associated with a risk of
      Meniere's disease; moreover, the OR for the Cav1 polymorphism and Meniere's
      disease risk was 1.849 (CI, 1.033-3.310) with adjustment for age and sex. In
      conclusion, the NOS3 and Cav1 polymorphisms were significantly associated with
      the risk of SSNHL and Meniere's disease, respectively.

PMID- 23560645
TI  - Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or
      photodynamic therapy: 12-month outcomes of a randomized controlled clinical
      trial.
AB  - OBJECTIVE: The objective of the study is to compare the clinical, microbiological
      and host-derived effects in the non-surgical treatment of initial peri
      implantitis with either adjunctive local drug delivery (LDD) or adjunctive
      photodynamic therapy (PDT) after 12 months. MATERIALS AND METHODS: Forty subjects
      with initial peri-implantitis, that is, pocket probing depths (PPD) 4-6 mm with
      bleeding on probing (BoP) and radiographic bone loss <=2 mm, were randomly
      assigned to two treatment groups. All implants were mechanically debrided with
      titanium curettes and with a glycine-based powder airpolishing system. Implants
      in the test group (N = 20) received adjunctive PDT, whereas minocycline
      microspheres were locally delivered into the peri-implant pockets of control
      implants (N = 20). At sites with residual BoP, treatment was repeated after 3, 6,
      9 and 12 months. The primary outcome variable was the change in the number of
      peri-implant sites with BoP. Secondary outcome variables included changes in PPD,
      clinical attachment level (CAL), mucosal recession (REC) and in bacterial counts
      and crevicular fluid (CF) levels of host-derived biomarkers. RESULTS: After 12
      months, the number of BoP-positive sites decreased statistically significantly (P
      < 0.05) from baseline in both groups (PDT: 4.03 +/- 1.66-1.74 +/- 1.37, LDD: 4.41
      +/- 1.47-1.55 +/- 1.26). A statistically significant (P < 0.05) decrease in PPD
      from baseline was observed at PDT-treated sites up to 9 months (4.19 +/- 0.55 mm
      to 3.89 +/- 0.68 mm) and up to 12 months at LDD-treated sites (4.39 +/- 0.77 mm
      to 3.83 +/- 0.85 mm). Counts of Porphyromonas gingivalis and Tannerella forsythia
      decreased statistically significantly (P < 0.05) from baseline to 6 months in the
      PDT and to 12 months in the LDD group, respectively. CF levels of IL-1beta
      decreased statistically significantly (P < 0.05) from baseline to 12 months in
      both groups. No statistically significant differences (P > 0.05) were observed
      between groups after 12 months with respect to clinical, microbiological and host
      derived parameters. CONCLUSIONS: Non-surgical mechanical debridement with
      adjunctive PDT was equally effective in the reduction of mucosal inflammation as
      with adjunctive delivery of minocycline microspheres up to 12 months. Adjunctive
      PDT may represent an alternative approach to LDD in the non-surgical treatment of
      initial peri-implantitis.

PMID- 23560646
TI  - Carbene generation by cytochromes and electronic structure of heme-iron-porphyrin
      carbene complex: a quantum chemical study.
AB  - Carbene-heme-iron-porphyrin complexes generated from cytochrome P450 (CYP450)
      mediated metabolism of compounds containing methylenedioxyphenyl (MDP) moiety
      lead to the mechanism-based inhibition (MBI) of CYPs. This coordination complex
      is termed as the metabolic-intermediate complex (MIC). The bioinorganic chemistry
      of MDP carbenes has been studied using quantum chemical methods employing density
      functional theory (B3LYP functional with implicit solvent corrections) to (i)
      analyze the characteristics of MDP-carbene in terms of singlet-triplet energy
      difference, protonation, and dimerization energies, etc.; (ii) determine the
      electronic structure and analyze the Fe-carbene interactions; and (iii) elucidate
      the potential reaction pathways for the generation of carbene, using Cpd I
      (iron(IV)-oxo-porphine with SH(-) as the axial ligand) as the model oxidant to
      mimic the activity of CYP450. The results show that MDP-carbenes are sufficiently
      stable and nucleophilic, leading to the formation of stable MIC (-40.35 kcal/mol)
      on the doublet spin state, formed via interaction between sigma(LP) of carbene
      and empty dz(2) orbital of heme-iron. This was aided by the back-bonding between
      filled d(xz) orbital of heme-iron and the empty p orbital of carbene. The
      mechanistic pathway proposed in the literature for the generation of MDP-carbene
      (CH hydroxylation followed by water elimination) was studied, and observed to be
      unfavorable, owing to the formation of highly stable hydroxylated product (-57.12
      kcal/mol). An intriguing pathway involving hydride ion abstraction and proton
      transfer followed by water elimination step was observed to be the most probable
      pathway.

PMID- 23560647
TI  - Cis carotenoids: colorful molecules and free radical quenchers.
AB  - We present a density functional theory (DFT) and time-dependent density
      functional theory (TD-DFT) study on the stability, antioxidant properties with
      respect to the single electron transfer mechanism, and electronic absorption
      spectra of some isomers (9-cis, 13-cis, and 15-cis) of carotenoids such as
      astaxanthin, lycopene, and those present in virgin olive oil (lutein, beta
      carotene, neoxanthin, antheraxanthin, violaxanthin, neochrome, luteoxanthin,
      mutatoxanthin, and violaxanthin). In general, the calculated relative stability
      of the cis isomers appears to be in line with experimental observations. It is
      predicted that the above-mentioned carotenoids (cis and trans isomers) will
      transfer one electron to the (*)OH radical. However, this transference is not
      plausible with radicals such as (*)OOH, (*)OC2H5, (*)OOC2H5, (*)NO2, and
      (*)OOCH2CH?CH2. On the other hand, some carotenoids (beta-carotene, lycopene,
      lutein, astaxanthin, violaxanthin, and antheraxanthin) will likely accept, in a
      medium of low polarity, one electron from the radical (*)O2(-). However,
      neoxanthin, auroxanthin, mutatoxanthin, luteoxanthin, and neochrome would not
      participate in such an electronic transfer mechanism. The TD-DFT studies show
      that neutral species of the cis and trans isomers maintain the same color. On the
      contrary, the ionic species undergo a "bleaching" process where the absorption
      wavelengths shift to longer values (>700 nm). Additionally, the formation of a
      complex between astaxanthin and Cu(2+) is explored as well as the effect that the
      metal atom will have in the UV-vis spectrum.

PMID- 23560648
TI  - Parasitism of immature stages of Haemaphysalis sulcata (Acari: Ixodidae) on some
      reptiles in Turkey.
AB  - Reptiles may contribute to maintaining tick populations by feeding larvae,
      nymphs, and adults. The life cycles and tick-host associations of many Turkish
      ticks are still poorly known, and only 3 ixodid tick species have been reported
      on 7 reptile species in Turkey. In this study, we performed a tick survey on
      reptiles in the Southeastern Anatolia Region of Turkey. In 2005, 57 reptiles (52
      lizards and 5 snakes) comprising 10 species from 5 families were captured and
      examined for tick infestation. A total of 427 ticks was collected. The majority
      of ticks found on lizards was the immature stages of Haemaphysalis sulcata, 420
      larvae and 4 nymphs. The only adult ticks recorded on the agamid lizard, Laudakia
      stellio, were Hyalomma aegyptium (1 ?, 2 ?). The highest tick infestation rate
      was recorded on specimens of Timon princeps. This study is the first detailed
      investigation on ticks infesting reptiles in Turkey. To the best of our
      knowledge, these tick-host associations have never been documented in the
      literature.

PMID- 23560649
TI  - Evidence of emerging hookah use among university students: a cross-sectional
      comparison between hookah and cigarette use.
AB  - BACKGROUND: The emergence of hookah is being noted on college campuses and in
      large U.S. cities and evidence points to an increasing trend for college
      students. The purpose of this study was to assess hookah use and identify
      associations with cigarette smoking and demographic factors. METHODS: An
      intercept sampling method was used at various locations on a large university
      campus in the southeastern United States, yielding a high participation rate
      (52%). A total of 1,203 participants completed a computer-aided survey that
      assessed the use of tobacco products. The sample characteristics were then
      weighted to match the University population of students enrolled during the same
      semester. Bivariate (chi-square and t-test) and multivariate (logistic
      regression) tests of association were conducted to assess differences between
      cigarette and hookah users. RESULTS: Hookah smoking exceeded cigarette smoking
      for both ever use (46.4% vs 42.1%) and past year use (28.4% vs 19.6%). Females
      and males used hookah at similar rates. Hispanic respondents had the highest
      prevalence of current use of hookah (18.9%) and cigarettes (16.4%). CONCLUSIONS:
      As hookah surpasses cigarette use, efforts need to be made to slow the increase
      in new tobacco products that are attractive to young adults and that pose many of
      the same health risks as those related to traditional tobacco products.
      Prevalence of all emerging tobacco products, including hookah, and the
      relationship with cigarette use needs to be monitored on an ongoing basis.

PMID- 23560650
TI  - Synthesis and biological evaluation of a new series of hexahydro-2H-pyrano[3,2
      c]quinolines as novel selective sigma1 receptor ligands.
AB  - The synthesis and pharmacological activity of a new series of hexahydro-2H
      pyrano[3,2-c]quinoline derivatives as potent sigma1 receptor (sigma1R) ligands
      are reported. This family, which does not contain the highly basic amino group
      usually present in other sigma1R ligands, showed high selectivity over the sigma2
      receptor (sigma2R). The activity was shown to reside in only one of the four
      possible diastereoisomers, which exhibited a perfect match with known sigma1R
      pharmacophores. A hit to lead program based on a high-throughput screening hit
      (8a) led to the identification of compound 32c, with substantially improved
      activity and physicochemical properties. Compound 32c also exhibited a good ADMET
      (absorption, distribution, metabolism, excretion, toxicity) profile and was
      identified as a sigma1R antagonist on the basis of its analgesic activity in the
      mouse capsaicin and formalin models of neurogenic pain.

PMID- 23560651
TI  - Pushing extended p-quinodimethanes to the limit: stable tetracyano-oligo(N
      annulated perylene)quinodimethanes with tunable ground states.
AB  - p-Quinodimethane (p-QDM) is a fundamental building block for the design of pi
      conjugated systems with low band gap and open-shell biradical character. However,
      synthesis of extended p-QDMs has usually suffered from their intrinsic high
      reactivity and poor solubility. In this work, benzannulation together with
      terminal cyano-substitution was demonstrated to be an efficient approach for the
      synthesis of a series of soluble and stable tetracyano-oligo(N-annulated
      perylene)quinodimethanes nPer-CN (n = 1-6), with the longest molecule having 12
      para-linked benzenoid rings! The geometry and electronic structures of these
      oligomers were investigated by steady-state and transient absorption
      spectroscopy, nuclear magnetic resonance, electron spin resonance,
      superconducting quantum interference device, and FT Raman spectroscopy assisted
      by density functional theory calculations. They showed tunable ground states,
      varying from a closed-shell quinoidal structure for monomer, to a singlet
      biradical for dimer, trimer, and tetramer, and to a triplet biradical for
      pentamer and hexamer. Large two-photon absorption cross-section values were
      observed in the near-infrared range, which also exhibited a clear chain-length
      dependence.

PMID- 23560652
TI  - Two-point discrimination in diabetic patients.
AB  - BACKGROUND: Diabetes mellitus (DM) is a common cause of polyneuropathy. The aim
      of the present study was to evaluate two-point discrimination (TPD) compared with
      nerve conduction studies in the early stages of DM. METHODS: Forty-eight patients
      with early diagnosed (<5 years) type 2 DM and 17 healthy controls were evaluated.
      Of the patients with DM, 26 had neuropathic pain and 22 were asymptomatic. TPD
      and electrophysiological evaluations was obtained for all subjects. RESULTS:
      Nerve conduction studies in patients showed findings related to both
      demyelination and axonal damage. Patients with neuropathic pain had higher TPD
      values on the plantar surface of the foot and both groups of DM patients had
      higher TPD values on the outer lateral malleolus compared with the control group
      (P < 0.05). There was a correlation between TPD and axonal damage in patients
      with neuropathic pain (P < 0.05). In patients without neuropathic pain, there was
      a correlation between TPD values and distal latencies of motor or sensory nerves
      (P < 0.05). In the control group, only third digit TPD values were related to the
      distal motor latency of the median nerve (P < 0.05). CONCLUSION: In conclusion,
      the TPD method is a less painful, practical, cost-effective, and more easily
      applicable method that was completed in less time than nerve conduction studies.
      Higher TPD values in the lower extremities indicate nerve damage in patients.
      These findings suggest that increased TPD values can easily determine neuropathy
      starting in the early stages of diabetes in patients with DM.

PMID- 23560653
TI  - Factors that affect proportional glomerular filtration rate after minimally
      invasive partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: Several factors have been shown to impact the overall
      glomerular filtration (GFR) rate after partial nephrectomy. Change in overall
      GFR, however, does not necessarily reflect the impact of these factors on the
      operated kidney. Using preoperative and postoperative renal scintigraphy, we
      sought to assess the impact of patient, tumor, and operative factors on GFR of
      the affected kidney (proportional GFR). PATIENTS AND METHODS: We identified 73
      patients who underwent minimally invasive partial nephrectomy with preoperative
      and postoperative renal scans from two institutions. Patient, tumor, and
      operative characteristics were recorded. We used multiple linear regression to
      determine the patient and clinical factors predictive of postoperative
      proportional GFR in the operated kidney. We tested for an interaction between
      preoperative proportional GFR and nephrometry score and ischemia. We further
      fitted two separate linear models to compare the proportion of variance (R(2))
      explained by ischemia time in change in renal function in the operated kidney
      with the change in renal function in both kidneys. RESULTS: Surgical parameters
      (procedure approach, ischemia time, and estimated blood loss) and preoperative
      proportional GFR were significantly associated with postoperative proportional
      GFR. Preoperative proportional GFR (beta=5.93, 95% confidence interval [CI]:
      3.88, 7.97, P<0.0005) and procedure approach (beta=8.67, 95% CI: 4.50, 12.80,
      P<0.0005) were strongly associated with outcome while ischemia time (beta=-1.80,
      95% CI: -3.48, -0.11, P=0.04) and estimated blood loss (beta=-1.15, 95% CI: 
      0.29, -0.01, P=0.04) just reached statistical significance. The interaction term
      between preoperative proportional GFR and nephrometry score or ischemia time was
      not statistically significant (nephrometry, P=0.2 continuous or P=0.6
      categorical, and ischemia, P=0.7, respectively). CONCLUSION: Lower preoperative
      proportional GFR, longer ischemia times, and higher blood loss all negatively
      impact postoperative proportional GFR while tumor complexity as gauged by
      morphometry scoring does not. Larger studies are needed to determine whether
      renal scintigraphy is a more accurate method of measuring the impact of the
      ischemia time on postoperative proportional GFR.

PMID- 23560654
TI  - Could minors be living kidney donors? A systematic review of guidelines, position
      papers and reports.
AB  - The purpose of this study is to systematically review guidelines, position
      papers, and reports on living kidney donation by minors. We systematically
      searched the databases such as Medline, Embase, ISI Web of knowledge, Google
      scholar as well as the websites of various bioethics committees, transplant
      organizations and societies. Guidelines were included if they provided
      recommendations for or against living kidney donation by minors. Data were
      analyzed using qualitative content analysis. We included 39 documents in this
      study. Twenty seven of these endorse an absolute prohibition of living kidney
      donation by minors, because of concerns regarding the decision-making capacity of
      minors, the impartiality of parental authorization, the best interests of the
      minor, and the necessity of the donation. Twelve guidelines, however, would
      exceptionally allow living kidney donation by minors, provided that adequate
      safeguards are put in place, including an assessment of the minor's autonomy and
      maturity, authorization by an independent body, assuring that the anticipated
      psychosocial benefits outweigh the medical and psychosocial risks for the donor
      and the restriction to situations of last resort. A more adequate medical and
      psychosocial follow-up of living kidney donors may likely contribute to a more
      unified approach towards living kidney donation by minors. 

PMID- 23560655
TI  - The robotic third arm as a competent analog of an assisting surgeon in radical
      gastrectomy: impact on short-term clinical outcomes.
AB  - BACKGROUND: Robotic surgery was invented to overcome difficulties associated with
      conventional laparoscopic surgery. However, ways in which to improve the efficacy
      of such surgery have not yet been discussed. This report focuses on the role of a
      robotic third arm in maximizing the efficacy of lymph node dissection in robot
      assisted gastrectomy. MATERIALS AND METHODS: Thirty-five robotic gastrectomies
      were performed between April 2009 and December 2010. We evaluated our surgical
      procedures by reviewing video recordings of robotic operations and analyzed the
      steps involved in lymph node dissections frame by frame. Then, we analyzed the
      short-term clinical outcomes to look at the impact of standardized use of the
      third arm on clinical outcomes. The initial 15 cases (Group A) were compared with
      20 later cases (Group B) in terms of postoperative inflammation and pancreatitis.
      RESULTS: The clinicopathologic characteristics, including operation type,
      hospital stay, morbidity, and pathological features, were not different between
      the two groups. However, postoperative serum amylase levels as well as drain
      amylase levels were significantly lower in Group B than in Group A (P<.05). The
      incidence of postoperative pancreatic fistula was also lower in Group B (P<.05).
      CONCLUSIONS: Gastrectomy with extragastric lymph node dissection using the da
      Vinci((r)) Surgical System (Intuitive Surgical, Sunnyvale, CA) can be performed
      safely and effectively with the appropriate and sophisticated use of a robotic
      third arm.

PMID- 23560656
TI  - Laparoscopic orchiopexy for intra-abdominal testes-a single institution review.
AB  - OBJECTIVE: To report success, complication, and atrophy rates, as well as cost
      analysis and surgeon preference, for standard laparoscopic versus laparoscopic
      Fowler-Stephens (FS) approaches to intra-abdominal testes. PATIENTS AND METHODS:
      The records of children who underwent laparoscopic orchiopexy for impalpable
      testes at our institution were reviewed. Two groups were assessed: Group 1, who
      underwent a standard laparoscopic orchiopexy; and Group 2, who underwent either a
      single-stage or two-stage FS orchiopexy. Success was defined as an intrascrotal
      testis without atrophy. Cost analysis was performed by obtaining operating room
      charges for the procedures. Surgeon preference was evaluated by calculating the
      number of each type of orchiopexy performed. RESULTS: From 1998 to 2005, 61
      laparoscopic orchiopexies were performed on 46 patients. In Group 1, 31
      orchiopexies were performed on 22 patients. In Group 2, 30 orchiopexies were
      performed in 26 patients. Eight orchiopexies were performed on 7 patients in a
      single stage, whereas 22 orchiopexies in 19 patients were performed in two
      stages. Two patients underwent both unilateral FS and laparoscopic orchiopexy.
      Success rates for Groups 1 and 2 were 96.7% and 83.3%, respectively. There were
      three complications in Group 1 (9.7%) and nine complications in Group 2 (30%).
      Atrophy rates for the two groups were 6.5% (2/31) and 16.7% (4/24), respectively.
      The average operating room cost for a standard laparoscopic approach was $3686,
      $3604 for the first stage and $3909 for the second stage of a two-stage FS
      approach, and $3785 for a single-stage FS approach. CONCLUSIONS: Data from this
      series suggest that completing a laparoscopic orchiopexy in a single operation
      without ligating the testicular vessels has comparable, if not better, success
      rates to those of FS procedures, while reducing cost and potentially reducing
      complications. Outcomes between single- and two-stage FS approaches are similar,
      but the former can be accomplished at half the cost.

PMID- 23560657
TI  - Successful endoscopic band ligation of esophageal perforation by fish bone
      ingestion.
AB  - Acute esophageal perforations by foreign body ingestion result in complications
      such as mediastinitis and retropharyngeal or parapharyngeal abscesses. Because
      the mortality of esophageal perforation is up to 22%, immediate treatment is
      critical. Herein, we report a case of successful endoscopic band ligation of
      esophageal perforation. A 68-year-old man was admitted complaining of substernal
      pain and dysphagia after ingesting a fish bone. Immediately emergency endoscopy
      was performed, and the fish bone was observed lodged in the lower esophagus.
      Although the fish bone was easily removed by an endoscopic rat-tooth forceps,
      esophageal perforation was found after the procedure. Endoscopic band ligation
      for perforation was performed. Initial chest computed tomography (CT) showed
      pneumomediastinum and local inflammation, but follow-up CT showed improved
      pneumomediastinum. The patient was given oral nutrition 2 weeks after procedure,
      and he was discharged without any complications. This case report emphasizes for
      the first time the availability of immediate endoscopic band ligation for acute
      esophageal perforation.

PMID- 23560658
TI  - Single-incision pediatric endosurgery: a systematic review.
AB  - BACKGROUND: Single-incision pediatric endosurgery (SIPES) is defined as minimally
      invasive surgery performed through a unique incision in the abdomen, chest, or
      retroperitoneum. Several publications exist, but no previous systematic review
      has been made to evaluate the real benefits of this approach in terms of
      feasibility and clinical outcomes. MATERIALS AND METHODS: We performed an
      electronic search in PubMed up to March 2012 with the terms "single AND incision
      OR site OR port OR trocar AND children" including related articles and obtained
      197 articles. After applying our inclusion criteria, 78 articles were reviewed.
      RESULTS: We identified prospective controlled trials (n=1), case-control studies
      (n=12), case series (n=49), and case reports (n=16). In total, 4212 patients had
      been operated on by SIPES and were separated by systems: gastrointestinal
      (n=2888), urologic (n=390), gynecologic (n=27), other abdominal (n=874), and
      thoracic (n=33) procedures. The most common procedure was SIPES appendectomy, and
      a unique prospective controlled trial supports its safety and effectiveness.
      Technically demanding surgeries such as hepatojejunostomy and colonic surgeries
      were described. Multichannel ports and multiple ports, standard and articulated
      instruments, transparietal instruments, retraction sutures, and magnets were
      used. Operative times, length of stay, and complications similar to standard
      laparoscopic surgery were described. A low conversion rate (to a reduced port,
      standard laparoscopy and open procedures) was also mentioned. No comparable
      measure for pain and cosmesis assessment was used. CONCLUSIONS: A wide experience
      in SIPES and feasibility has already been described with good clinical outcomes
      and low rate of conversion. Appendectomy is the unique procedure in which SIPES
      has been demonstrated to be safe and effective. It is pending the execution of
      prospective controlled trials for other operations to demonstrate, with objective
      evidence, the real benefits of this less invasive approach.

PMID- 23560659
TI  - Efficacy of laparoscopic gastric mobilization for esophagectomy: comparison with
      open thoraco-abdominal approach.
AB  - BACKGROUND: Less invasive esophagectomy using laparoscopic or thoracoscopic
      surgery has been reported to have the advantages in short-term recovery over the
      conventional open thoraco-abdominal approach. However, few reports directly
      compare laparoscopic gastric mobilization (LGM) and thoracotomy with laparotomy
      and thoracotomy. The aim of this study was to prove the clinical efficacy of LGM
      compared with open thoraco-abdominal esophagectomy (OE) in treating thoracic
      esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 92
      consecutive patients who underwent esophagectomy by OE (n=47) or LGM (n=45)
      between 1999 and 2009 at Kochi Medical School (Kochi, Japan) to analyze the
      surgical outcomes. RESULTS: Patients who underwent LGM had significantly lower
      operative blood loss (430 versus 1060 mL; P<.001), lower rate of postoperative
      infections (POIs) (33.3 versus 55.3%; P=.034), shorter length of intensive care
      unit stay (1 versus 3 days; P<.001), and hospital stay (35 versus 46 days;
      P=.003). CONCLUSIONS: LGM has clinical benefits compared with OE in reduced POIs
      and faster recovery for patients with esophageal cancer.

PMID- 23560660
TI  - Expression of the human FSHD-linked DUX4 gene induces neurogenesis during
      differentiation of murine embryonic stem cells.
AB  - Misexpression of the double homeodomain protein DUX4 in muscle is believed to
      cause facioscapulohumeral muscular dystrophy (FSHD). Although strategies are
      being devised to inhibit DUX4 activity in FSHD, there is little known about the
      normal function of this protein. Expression of DUX4 has been reported in
      pluripotent cells and testis. To test the idea that DUX4 may be involved in
      initiating a germ lineage program in pluripotent cells, we interrogated the
      effect of expressing the human DUX4 gene at different stages during in vitro
      differentiation of murine embryonic stem (ES) cells. We find that expression of
      even low levels of DUX4 is incompatible with pluripotency: DUX4-expressing ES
      cells downregulate pluripotency markers and rapidly differentiate even in the
      presence of leukemia inhibitory factor (LIF) and bone morphogenetic protein 4
      (BMP4). Transcriptional profiling revealed unexpectedly that DUX4 induced a
      neurectodermal program. Embryoid bodies exposed to a pulse of DUX4 expression
      displayed severely inhibited mesodermal differentiation, but acquired neurogenic
      potential. In a serum-containing medium in which neurogenic differentiation is
      minimal, DUX4 expression served as a neural-inducing factor, enabling the
      differentiation of Tuj1+ neurites. These data suggest that besides effects in
      muscle and germ cells, the involvement of DUX4 in neurogenesis should be
      considered as anti-DUX4 therapies are developed. 

PMID- 23560661
TI  - The role of trait-affect, depression, and anxiety in women with sexual
      dysfunction: a pilot study.
AB  - Despite the increasing number of studies, it is not yet clear how emotions affect
      sexual response in women with and without sexual problems. The aim of this study
      was to explore the relation among trait-affect, depression, anxiety, and sexual
      functioning. Participants were 237 women: 167 without sexual problems, 37 with
      low levels of sexual functioning, and 17 with sexual dysfunction. Participants
      completed the Positive and Negative Affect Schedule, the Brief Symptom Inventory,
      the Beck Depression Inventory, and the Female Sexual Function Index. Results
      showed that women with sexual problems presented lower levels of positive trait
      affect in comparison with women without sexual problems. Mediation analysis
      indicated that depression mediated 44% of the total effect of positive trait
      affect and 83% of the total effect of negative trait-affect on sexual
      functioning. Moreover, anxiety (Brief Symptom Inventory subscale) mediated 18% of
      the total effect of positive trait-affect on sexual functioning and 61% of the
      total effect of negative trait-affect on sexual functioning. These results may
      help explain the high comorbidity among sexual dysfunction, depression, and
      anxiety, and raise the hypothesis that trait-affect may act as a common
      vulnerability factor for these clinical conditions.

PMID- 23560662
TI  - Succession of bacterial and fungal 4-chloro-2-methylphenoxyacetic acid degraders
      at the soil-litter interface.
AB  - Phenoxyacetic acids can be degraded by diverse soil microorganisms. Nevertheless,
      we miss information about the succession of 4-chloro-2-methylphenoxyacetic acid
      (MCPA) degraders in micro-environments of soils as well as specific functions of
      different microbial groups during MCPA degradation. We studied MCPA degradation
      at the soil-litter interface in a microcosm experiment and followed the
      succession of different degrader populations by quantifying the abundance of 16S
      rRNA genes as well as, the fungal ITS fragment and the functional genes tfdA (in
      total and divided into three classes) and cadA. Adjacent to the litter layer, a
      dynamic depletion zone of MCPA indicated that the litter effect on MCPA
      degradation depends on substrate availability and the affected soil volume. The
      increase of the tfdA class III and cadA genes was linked to MCPA mineralisation.
      Total abundance of tfdA genes was dominated by class I MCPA degraders and did not
      reflect MCPA degradation potential of the soil. Litter addition induced the
      development of pioneer and late-stage fungal communities, which were probably
      both involved in MCPA degradation. The results underline the importance of the
      ecological behaviour of different degrader populations for the understanding of
      herbicide degradation in soils. 

PMID- 23560663
TI  - Family emotion expressivity, emotion regulation, and the link to psychopathology:
      examination across race.
AB  - Research has established links between parental emotion socialization behaviours
      and youth emotional and psychological outcomes; however, no study has
      simultaneously compared these relations for White, Black, and Asian individuals.
      In this study, emerging adults identifying as White (n= 61), Black (n= 51), or
      Asian (n= 56) retrospectively reported on parents' emotion socialization
      behaviours during childhood, existing emotion regulation (ER) skills, and current
      psychopathology symptoms. Asian participants reported fewer positive displays of
      emotions in their families during childhood than White and Black participants.
      Despite this difference, low expression of positive emotions in families during
      childhood did not relate to negative outcomes for Asian participants but was
      linked for White and Black participants. Overall, Asian participants reported
      more difficulties with ER than Black or White participants, and relations between
      ER difficulties and psychopathology varied by racial group. The findings
      emphasize the need to consider race when conducting research on emotion
      functioning with families and highlight emotion dysregulation as a potential
      treatment target for White, Black, and Asian individuals.

PMID- 23560664
TI  - The role of outcome inhibition in interference between outcomes: a contingency
      learning analogue of retrieval-induced forgetting.
AB  - Current associative theories of contingency learning assume that inhibitory
      learning plays a part in the interference between outcomes. However, it is
      unclear whether this inhibitory learning results in the inhibition of the outcome
      representation or whether it simply counteracts previous excitatory learning so
      that the outcome representation is neither activated nor inhibited. Additionally,
      these models tend to conceptualize inhibition as a relatively transient and cue
      dependent state. However, research on retrieval-induced forgetting suggests that
      the inhibition of representations is a real process that can be relatively
      independent of the retrieval cue used to access the inhibited information.
      Consistent with this alternative view, we found that interference between
      outcomes reduces the retrievability of the target outcome even when the outcome
      is associated with a novel (non-inhibitory) cue. This result has important
      theoretical implications for associative models of interference and shows that
      the empirical facts and theories developed in studies of retrieval-induced
      forgetting might be relevant in contingency learning and vice versa.

PMID- 23560665
TI  - Cross-modal facilitation of mental rotation: effects of modality and complexity.
AB  - Performance in a visual mental rotation (MR) task has been reported to predict
      the ability to recognize retrograde-transformed melodies. The current study
      investigated the effects of melodic structure on the MR of sequentially presented
      visual patterns. Each trial consisted of a five-segment sequentially presented
      visual pattern (standard) followed by a five-tone melody that was either
      identical in structure to the standard or its retrograde. A visual target pattern
      was either the rotated version of the standard or unrelated to it. The task was
      to indicate whether the target pattern was a rotated version of the standard or
      not. Periodic patterns were not rotated but melodies facilitated the rotation of
      non-periodic patterns. For these, rotation latency was determined by a
      quantitative index of complexity (number of runs). This study provides the first
      experimental confirmation for cross-modal facilitation of MR.

PMID- 23560666
TI  - Integration of base rates and new information in an abstract hypothesis-testing
      task.
AB  - In two studies, we investigated how people use base rates and the presence versus
      the absence of new information to judge which of two hypotheses is more likely.
      Participants were given problems based on two decks of cards printed with 0-4
      letters. A table showed the relative frequencies of the letters on the cards
      within each deck. Participants were told the letters that were printed on or
      absent from a card the experimenter had drawn. Base rates were conveyed by
      telling participants that the experimenter had chosen the deck by drawing from an
      urn containing, in different proportions, tickets marked either 'deck 1' or 'deck
      2'. The task was to judge from which of the two decks the card was most likely
      drawn. Prior probabilities and the evidential strength of the subset of present
      clues (computed as 'weight of evidence') were the only significant predictors of
      participants' dichotomous (both studies) and continuous (Study 2) judgments. The
      evidential strength of all clues was not a significant predictor of participants'
      judgments in either study, and no significant interactions emerged. We discuss
      the results as evidence for additive integration of base rates and the new
      present information in hypothesis testing.

PMID- 23560667
TI  - Are stepfathers' education levels associated with the intelligence of their
      stepsons? A register-based study of Norwegian half-brothers.
AB  - We examined the relationship between the parents' education levels and the adult
      intelligence of their children in a population-based, nationwide sample of
      Norwegian half-brothers with different fathers (2,016 pairs of half-brothers). In
      a family where the mother has two children with different men, the firstborn
      child usually lives with the younger child's father during a period of their
      childhood. This makes it possible to study the non-genetic effects of paternal
      education on children's development. Results showed that the education level of
      the younger half-brother's father was positively associated with the intelligence
      score of the older half-brother. The education level of the older half-brother's
      father was not associated with the intelligence score of the younger half
      brother. Firstborn men whose half-brothers' fathers had high levels of education
      had intelligence scores that were 33% (95% confidence interval: 18-47%) of a
      standard deviation higher than those of firstborn men whose half-brothers'
      fathers had low levels of education, after adjustment for the biological fathers'
      education levels, mothers' education levels, and other background factors. These
      findings are compatible with the hypothesis that a child's family environment
      exerts an effect on the cognitive abilities of the child that lasts into
      adulthood.

PMID- 23560668
TI  - 'Beauty is in the eye of the beer holder': people who think they are drunk also
      think they are attractive.
AB  - This research examines the role of alcohol consumption on self-perceived
      attractiveness. Study 1, carried out in a barroom (N= 19), showed that the more
      alcoholic drinks customers consumed, the more attractive they thought they were.
      In Study 2, 94 non-student participants in a bogus taste-test study were given
      either an alcoholic beverage (target BAL [blood alcohol level]= 0.10 g/100 ml) or
      a non-alcoholic beverage, with half of each group believing they had consumed
      alcohol and half believing they had not (balanced placebo design). After
      consuming beverages, they delivered a speech and rated how attractive, bright,
      original, and funny they thought they were. The speeches were videotaped and
      rated by 22 independent judges. Results showed that participants who thought they
      had consumed alcohol gave themselves more positive self-evaluations. However,
      ratings from independent judges showed that this boost in self-evaluation was
      unrelated to actual performance.

PMID- 23560669
TI  - Perceived facial adiposity conveys information about women's health.
AB  - Although several prominent theories of human facial attractiveness propose that
      some facial characteristics convey information about people's health, empirical
      evidence for this claim is somewhat mixed. While most previous research into this
      issue has focused on facial characteristics such as symmetry, averageness, and
      sexual dimorphism, a recent study reported that ratings of facial adiposity
      (i.e., perceptions of fatness in the face) were positively correlated with
      indices of poor physical condition in a sample of young adults (i.e., reported
      past health problems and measures of cardiovascular fitness). These findings are
      noteworthy, since they suggest that perceived adiposity is a potentially
      important facial cue of health that has been overlooked by much of the previous
      work in this area. Here, we show that ratings of young adult women's facial
      adiposity are (1) better predicted by their body weight than by their body shape
      (Studies 1 and 2), (2) correlated with a composite measure of their physical and
      psychological condition (Study 2), and (3) negatively correlated with their trait
      (i.e., average) salivary progesterone levels (Study 3). Together, these findings
      present further evidence that perceived facial adiposity, or a correlate thereof,
      conveys potentially important information about women's actual health.

PMID- 23560670
TI  - Manual tapping enhances visual short-term memory performance where visual and
      motor coordinates correspond.
AB  - Visuo-manual interaction in visual short-term memory (VSTM) has been investigated
      little, despite its importance in everyday tasks requiring the coordination of
      visual perception and manual action. This study examines the influence of a
      manual action performed during stimulus learning on a subsequent VSTM test for
      object appearance. The memory display comprised a sequence of briefly presented
      1/f noise discs (i.e., possessing spectral properties akin to natural images),
      wherein each new stimulus was presented at a unique screen location. Participants
      either did (or did not) perform a concurrent manual action (spatial tapping) task
      requiring that a hand-held stylus be moved to a position on a touch tablet that
      corresponded (or did not correspond) to the screen position of each new stimulus
      as it appeared. At test, a single stimulus was presented, either at one of the
      original screen positions, or at a new position. Two factors were examined: the
      execution (or otherwise) of spatial tapping at a corresponding or non
      corresponding position, and the presentation of test stimuli either at their
      original spatial positions, or at new positions. We find that spatial tapping at
      corresponding positions elevates VSTM performance by more than 15%, but this
      occurs only when stimulus positions are matched from memory to test display. Our
      findings suggest that multimodal attentional focus during stimulus encoding
      (incorporating visual, spatial, and manual components) leads to stronger, more
      robust memory representations. We posit several possible explanations for this
      effect.

PMID- 23560671
TI  - Predictors of semantic categorical flexibility in older adults.
AB  - This study investigated the processes involved in the aging of semantic
      categorical flexibility. A previous study revealed the effects of aging on the
      flexible use of taxonomic relations. We aimed to explain our previous results
      regarding the performance of older adults; we carried out investigations into the
      respective roles of executive and conceptual factors in semantic categorical
      flexibility. Fifty older adults carried out a semantic categorical flexibility
      task alongside conceptual and executive measures. The results replicate our
      previous findings and indicate that the predictors of the maintenance of the use
      of taxonomic relations are conceptual and the predictors of the switching from
      thematic to taxonomic relations are executive.

PMID- 23560672
TI  - Altruism in social networks: evidence for a 'kinship premium'.
AB  - Why and under what conditions are individuals altruistic to family and friends in
      their social networks? Evolutionary psychology suggests that such behaviour is
      primarily the product of adaptations for kin- and reciprocal altruism, dependent
      on the degree of genetic relatedness and exchange of benefits, respectively. For
      this reason, individuals are expected to be more altruistic to family members
      than to friends: whereas family members can be the recipients of kin and
      reciprocal altruism, friends can be the recipients of reciprocal altruism only.
      However, there is a question about how the effect of kinship is implemented at
      the proximate psychological level. One possibility is that kinship contributes to
      some general measure of relationship quality (such as 'emotional closeness'),
      which in turn explains altruism. Another possibility is that the effect of
      kinship is independent of relationship quality. The present study tests between
      these two possibilities. Participants (N= 111) completed a self-report
      questionnaire about their willingness to be altruistic, and their emotional
      closeness, to 12 family members and friends at different positions in their
      extended social networks. As expected, altruism was greater for family than
      friends, and greater for more central layers of the network. Crucially, the
      results showed that kinship made a significant unique contribution to altruism,
      even when controlling for the effects of emotional closeness. Thus, participants
      were more altruistic towards kin than would be expected if altruism was dependent
      on emotional closeness alone - a phenomenon we label a 'kinship premium'. These
      results have implications for the ongoing debate about the extent to which kin
      relations and friendships are distinct kinds of social relationships, and how to
      measure the 'strength of ties' in social networks.

PMID- 23560673
TI  - Molecular basis of quantitative fibrinogen disorders in 27 patients from India.
AB  - Congenital fibrinogen deficiency is an extremely rare (1:1 000 000) hereditary
      bleeding disorder caused by defects in genes coding for fibrinogen Aalpha-, Bbeta
      and gamma-chains, respectively. We report here the molecular basis of fibrinogen
      deficiency in a large series of patients from India. Twenty-seven patients with
      clinical features suggestive of fibrinogen deficiency and with prolonged plasma
      clotting times and low fibrinogen levels were studied. Genomic DNA was screened
      for mutations in the fibrinogen alpha (FGA), beta (FGB), gamma (FGG) genes by PCR
      and conformation sensitive gel electrophoresis. Fourteen different disease
      causing mutations including frameshifts (51.9%), splice site (22.2%), missense
      (18.5%) and nonsense mutation (7.4%) were identified in 27 patients. Thirteen of
      them were novel, including seven frameshifts (fibrinogen Aalpha: p.Asp296 fs*59,
      p.Thr466 fs*17 and p.Lys575 fs*74; fibrinogen Bbeta: p.Gly414 fs*2 and fibrinogen
      gamma: p.Ser81 fs*5, p.Lys185 fs*13 and p.Asp278_279 fs*17), three splice site
      mutations (FGA gene c.364+1G>A; c.510+2 T>G; FGB gene c.851+1G>A), two missense
      substitutions (fibrinogen Bbeta: p.Gly288Ser; p.Arg445Thr) and a nonsense
      mutation in fibrinogen Aalpha (p.Tyr127*). Two common mutations (FGA: c.364+1G>A,
      n = 6, FGG: p.Lys185 fs*13, n = 7) affecting 13 patients were identified in this
      series, suggesting that these mutations could be screened first in Indian
      patients with fibrinogen deficiency. The molecular data presented here is the
      largest series of patients with fibrinogen deficiency reported so far, adding
      significantly to the mutation database of this condition. It also helps create an
      algorithm for its genetic diagnosis in India.

PMID- 23560674
TI  - Creatine supplementation does not decrease oxidative stress and inflammation in
      skeletal muscle after eccentric exercise.
AB  - Thirty-six male rats were used; divided into 6 groups (n = 6): saline; creatine
      (Cr); eccentric exercise (EE) plus saline 24 h (saline + 24 h); eccentric
      exercise plus Cr 24 h (Cr + 24 h); eccentric exercise plus saline 48 h (saline +
      48 h); and eccentric exercise plus Cr 48 h (Cr + 48 h). Cr supplementation was
      administered as a solution of 300 mg . kg body weight(-1) . day(-1) in 1 mL
      water, for two weeks, before the eccentric exercise. The animals were submitted
      to one downhill run session at 1.0 km . h(-1) until exhaustion. Twenty-four and
      forty-eight hours after the exercise, the animals were killed, and the quadriceps
      were removed. Creatine kinase levels, superoxide production, thiobarbituric acid
      reactive substances (TBARS) level, carbonyl content, total thiol content,
      superoxide dismutase, catalase, glutathione peroxidase, interleukin-1b (IL
      1beta), nuclear factor kappa B (NF-kb), and tumour necrosis factor (TNF) were
      analysed. Cr supplementation neither decreases Cr kinase, superoxide production,
      lipoperoxidation, carbonylation, total thiol, IL-1beta, NF-kb, or TNF nor alters
      the enzyme activity of superoxide dismutase, catalase, and glutathione peroxides
      in relation to the saline group, respectively (P < 0.05). There are positive
      correlations between Cr kinase and TBARS and TNF-alpha 48 hours after eccentric
      exercise. The present study suggests that Cr supplementation does not decrease
      oxidative stress and inflammation after eccentric contraction.

PMID- 23560675
TI  - The costs of transfusion: economic evaluations in transfusion medicine, Part 1.

PMID- 23560676
TI  - On the repair of oxidative damage to apoferritin: a model study with the
      flavonoids quercetin and rutin in aerated and deaerated solutions.
AB  - Ferritin (Ft) impairment through (*)O2(-), H2O2, and (*)OH production occurs in
      the cases of ketoses, diabetes mellitus, acute intermittent porphyria and
      tyrosinemia. In addition to (*)Trp and TyrO(*) radical production, ferrous iron
      liberation and Ft synthesis stimulation, site-specific oxidation reactions are
      induced leading to toxic iron accumulation in organs with high Ft content, for
      example, liver and brain. To elucidate the potential pathways to Ft recovery,
      repair of oxidative damage to horse spleen apoferritin (apoFt) and Ft by
      quercetin (QH) or rutin (RH) was studied in the presence and absence of oxygen.
      (*)Trp and TyrO(*) radicals were produced in pulse radiolysis through apoFt
      oxidation by (*)Br2(-) radicals. QH and RH bind to apoFt on eight sites with
      binding constants of ~80,000 and ~32,000 M(-1), respectively. In deaerated
      solutions, a repair of apoFt radicals is observed involving both bound and free
      flavonoids. This repair occurs by a fast intra- and a slow inter-molecular
      electron transfer from bound and free flavonoids, respectively. With QH, the rate
      constants are 10(4) s(-1) and 3.5 * 10(7) M(-1) s(-1) for the intra- and
      intermolecular repair reactions, respectively. Oxygen does not interfere with
      repair of apoFt or Ft by bound QH but inhibits 90% of Ft repair by RH. These
      results taken together indicate that flavonoid antioxidants may help alleviate Ft
      impairment in diseases involving an oxidative stress.

PMID- 23560677
TI  - Mycobacterium tuberculosis utilizes a unique heterotetrameric structure for
      dehydrogenation of the cholesterol side chain.
AB  - Compounding evidence supports the important role in pathogenesis that the
      metabolism of cholesterol by Mycobacterium tuberculosis plays. Elucidating the
      pathway by which cholesterol is catabolized is necessary to understand the
      molecular mechanism by which this pathway contributes to infection. On the basis
      of early metabolite identification studies in multiple actinomycetes, it has been
      proposed that cholesterol side chain metabolism requires one or more acyl-CoA
      dehydrogenases (ACADs). There are 35 genes annotated as encoding ACADs in the M.
      tuberculosis genome. Here we characterize a heteromeric ACAD encoded by Rv3544c
      and Rv3543c, formerly named fadE28 and fadE29, respectively. We now refer to
      genes Rv3544c and Rv3543c as chsE1 and chsE2, respectively, in recognition of
      their validated activity in cholesterol side chain dehydrogenation. Analytical
      ultracentrifugation and liquid chromatography-ultraviolet experiments establish
      that ChsE1-ChsE2 forms an alpha(2)beta(2) heterotetramer, a new architecture for
      an ACAD. Our bioinformatic analysis and mutagenesis studies reveal that
      heterotetrameric ChsE1-ChsE2 has only two active sites. E241 in ChsE2 is required
      for catalysis of dehydrogenation by ChsE1-ChsE2. Steady state kinetic analysis
      establishes the enzyme is specific for an intact steroid ring system versus
      hexahydroindanone substrates with specificity constants (k(cat)/K(M)) of (2.5 +/-
      0.5) * 10(5) s(-1) M(-1) versus 9.8 * 10(2) s(-1) M(-1), respectively, at pH 8.5.
      The characterization of a unique ACAD quaternary structure involved in sterol
      metabolism that is encoded by two distinct cistronic ACAD genes opens the way to
      identification of additional sterol-metabolizing ACADs in M. tuberculosis and
      other actinomycetes through bioinformatic analysis.

PMID- 23560678
TI  - Expanded vs. dense polytetrafluoroethylene membranes in vertical ridge
      augmentation around dental implants: a prospective randomized controlled clinical
      trial.
AB  - OBJECTIVE: This prospective randomized controlled trial was designed to test the
      performance of titanium-reinforced dense polytetrafluoroethylene (d-PTFE)
      membrane vs. titanium-reinforced expanded polytetrafluoroethylene (e-PTFE)
      membrane in achieving vertical bone regeneration, both associated with a
      composite grafting material. MATERIAL AND METHODS: The study enrolled 23 patients
      requiring bone augmentation with guided bone regeneration (GBR) procedures for
      placing implants in atrophic posterior mandibles (available bone height <7 mm).
      Implants were inserted and left to protrude from the bone level to achieve the
      programmed amount of vertical regeneration. Defects were filled with a composite
      bone graft (50% autologous bone and 50% mineralized bone allograft) and randomly
      covered with either an e-PTFE membrane (control) or a d-PTFE membrane (test).
      Membrane removal was performed after 6 months, and changes in bone height were
      recorded. RESULTS: Seventy-eight implants were inserted in 26 mandibular sites
      contextually to vertical ridge augmentation procedures. The healing period was
      uneventful in all sites, and the vertical defects were satisfactorily filled with
      a newly formed hard tissue. Mean defect fill after 6 months was 5.49 mm (SD +/-
      1.58) at test sites and 4.91 mm (SD +/- 1.78) at control sites. The normalized
      data (percentage changes against baseline) did not show any statistically
      significant difference between test and control groups (P = NS). CONCLUSIONS:
      Based on the data from this study, both d-PTFE and e-PTFE membranes showed
      identical clinical results in the treatment of vertical bone defects around
      implants, using the GBR technique. The membrane removal procedure was easier to
      perform in the d-PTFE group than in the e-PTFE group.

PMID- 23560679
TI  - Total synthesis of (-)-blepharocalyxin D and analogues.
AB  - An efficient strategy for the total synthesis of (-)-blepharocalyxin D and an
      analogue is described. The key step involves an acid-mediated cascade process in
      which reaction of methyl 3,3-dimethoxypropanoate with gamma,delta-unsaturated
      alcohols possessing diastereotopic styrenyl groups gives trans-fused bicyclic
      lactones with the creation of two rings and four stereocenters in one pot.

PMID- 23560680
TI  - Bilayer mott system with cation...anion supramolecular interactions based on a
      nickel dithiolene anion radical: coexistence of ferro- and antiferromagnetic
      anion layers and large negative magnetoresistance.
AB  - A novel bilayer Mott system, (Et-4BrT)[Ni(dmit)2]2 (Et-4BrT = ethyl-4
      bromothiazolium; dmit = 1,3-dithiole-2-thione-4,5-dithiolate), contains two
      nonequivalent Ni(dmit)2 anion layers, where both layers form Mott insulating
      states. Supramolecular Br(cation)...S(anion) and S(cation)...S(anion)
      interactions play a crucial role in constructing the bilayer structure. The ferro
      and antiferromagnetic short-range-ordering layers coexist in the crystal, which
      achieves large negative magnetoresistance (Deltarho/rho0 ~ -75% at 70 kOe) at 5 K
      under 1 GPa.

PMID- 23560681
TI  - Pulse laser photolysis of aqueous ozone in the microsecond range studied by time
      resolved far-ultraviolet absorption spectroscopy.
AB  - Chemical dynamics of an ozone (O3) pulse-photolytic reaction in aqueous solutions
      were studied with pump-probe transient far-ultraviolet (FUV) absorption
      spectroscopy. With a nanosecond pulse laser of 266 nm as pump light, transient
      spectra of O3 aqueous solutions (78-480 MUM, pH 2.5-11.3) were acquired in the
      time range from -50 to 50 MUs in the wavelength region from 190 to 225 nm. The
      measured transient spectra were linearly decomposed into the molar absorption
      coefficients and the concentration-time profiles of constituted chemical
      components with a multivariate curve resolution method. From the dependences of
      the time-averaged concentrations for 20 MUs of the constituted chemicals on the
      initial concentration of O3, it was found that the transient spectra involve the
      decomposition of O3 and the formation of hydrogen peroxide (H2O2) and a third
      component that is assigned to hydroxyl radical (OH) or perhydroxyl radical (HO2).
      Furthermore, the pH dependence of the time-averaged concentration of the third
      components indicates that HO2 is more probable than OH as the third component.
      The time-averaged concentration ratio of each chemical component to the initial
      O3 concentration depends on the pH conditions from -0.95 to -0.60 for O3, 0.98 to
      1.2 for H2O2, 0.002 to 0.29 for OH, and 0.012 to 0.069 for HO2.

PMID- 23560682
TI  - Incidence of AIDS-defining cancers and virus-related and non-virus-related non
      AIDS-defining cancers among HIV-infected patients compared with the general
      population in a large health district of Northern Italy, 1999-2009.
AB  - OBJECTIVES: The aim of the study was to investigate the incidence of AIDS
      defining cancers (ADCs) and virus-related and non-virus-related non-AIDS-defining
      cancers (NADCs) in HIV-infected patients compared with the general population,
      and to assess the risk factors associated with these malignancies. METHODS: We
      performed a retrospective cohort study for the period from 1999 to 2009 of HIV
      infected patients residing in the Local Health Authority of Brescia (northern
      Italy). Observed cancers in patients with HIV infection were compared with
      expected cancers in the population living in the same area using standardized
      incidence ratios (SIRs). Risk factors were assessed using Poisson regression
      analysis. RESULTS: A total of 5090 HIV-infected patients were included in the
      study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV
      infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non
      virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk
      (SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess
      of ADCs (SIR = 31.0) and virus-related NADCs (SIR = 12.3) was observed in HIV
      infected patients, while the excess risk for non-virus-related NADCs was small
      (SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for
      Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related
      NADCs, SIRs for a broad range of malignancies were close to unity. In
      multivariate analysis, increasing age and CD4 cell count < 50 cells/MUL were the
      only factors independently associated with all cancers. CONCLUSIONS: Among HIV
      infected people there was an excess of ADCs and also of NADCs, particularly those
      related to viral infections. Ageing and severe immunodeficiency were the
      strongest predictors.

PMID- 23560683
TI  - A novel tri-enzyme system in combination with laser-driven NMR enables efficient
      nuclear polarization of biomolecules in solution.
AB  - NMR is an extremely powerful, yet insensitive technique. Many available nuclear
      polarization methods that address sensitivity are not directly applicable to low
      concentration biomolecules in liquids and are often too invasive. Photochemically
      induced dynamic nuclear polarization (photo-CIDNP) is no exception. It needs high
      power laser irradiation, which often leads to sample degradation, and
      photosensitizer reduction. Here, we introduce a novel tri-enzyme system that
      significantly overcomes the above challenges, rendering photo-CIDNP a practically
      applicable technique for NMR sensitivity enhancement in solution. The specificity
      of the nitrate reductase (NR) enzyme is exploited to selectively in situ
      reoxidize the reduced photo-CIDNP dye FMNH2. At the same time, the oxygen
      scavenging ability of glucose oxidase (GO) and catalase (CAT) is synergistically
      employed to prevent sample photodegradation. The resulting tri-enzyme system (NR
      GO-CAT) enables prolonged sensitivity-enhanced data collection in 1D and 2D
      heteronuclear NMR, leading to the highest photo-CIDNP sensitivity enhancement (48
      fold relative to SE-HSQC) achieved to date for amino acids and polypeptides in
      solution. NR-GO-CAT extends the concentration limit of photo-CIDNP NMR down to
      the low micromolar range. In addition, sensitivity (relative to the reference SE
      HSQC) is found to be inversely proportional to sample concentration, paving the
      way for the future analysis of even more diluted samples.

PMID- 23560684
TI  - Characteristics, circumstances and toxicology of sudden or unnatural deaths
      involving very high-range alcohol concentrations.
AB  - AIMS: To characterize sudden or unnatural deaths with very high-range blood
      alcohol concentrations (BACs) presenting to the Department of Forensic Medicine
      (DOFM) in Sydney between 1 January 1997 and 31 December 2011. DESIGN: Case
      series. SETTING: Sydney, Australia. CASES: A total of 263 cases of sudden or
      unnatural death with a BAC of >=0.300 g/100 ml. MEASUREMENTS: Case
      characteristics, circumstances of death, quantitative toxicology, major autopsy
      findings and serology. FINDINGS: The mean age of decedents was 46.7 years and
      74.5% were male. Pre-existing alcohol problems were noted in 78.7%. Deaths were
      due to alcohol toxicity/chronic alcoholism (35.0%), combined alcohol/other drug
      toxicity (14.8%), accidents (18.6%), natural disease (13.3%), suicide (11.0%),
      homicide (6.8%) and one case was undetermined. Alcohol was a direct, or
      contributory, cause of death in 84.4% of cases. The overwhelming majority (81.4%)
      occurred in a home environment, and deaths did not vary by day or month. The mean
      BAC was 0.371 g/100 ml (range 0.300-0.820 g/100 ml), being highest in alcohol
      toxicity/chronic alcoholism cases (0.410 g/100 ml). The most frequently detected
      substances, other than alcohol, were benzodiazepines (31.9%) and opioids (12.9%).
      Alcohol-related disease was diagnosed in 62.9% of cases. Alcohol-related
      pathology was prevalent across all categories of death: severe steatosis (35.3%),
      cirrhosis (22.5%), chronic pancreatitis (15.3%), cardiomyopathy (9.4%) and
      cerebellar atrophy (9.0%). CONCLUSIONS: Unnatural deaths with very high-range
      alcohol concentrations extend well beyond direct toxicity, and alcohol is causal
      in most cases. Those at greatest risk are middle-aged males, with long histories
      of alcohol problems.

PMID- 23560686
TI  - Pyrolysis pathways of sulfonated polyethylene, an alternative carbon fiber
      precursor.
AB  - Polyethylene is an emerging precursor material for the production of carbon
      fibers. Its sulfonated derivative yields ordered carbon when pyrolyzed under
      inert atmosphere. Here, we investigate its pyrolysis pathways by selecting n
      heptane-4-sulfonic acid (H4S) as a model compound. Density functional theory and
      transition state theory were used to determine the rate constants of pyrolysis
      for H4S from 300 to 1000 K. Multiple reaction channels from two different
      mechanisms were explored: (1) internal five-centered elimination (Ei5) and (2)
      radical chain reaction. The pyrolysis of H4S was simulated with kinetic Monte
      Carlo (kMC) to obtain thermogravimetric (TGA) plots that compared favorably to
      experiment. We observed that at temperatures <550 K, the radical mechanism was
      dominant and yielded the trans-alkene, whereas cis-alkene was formed at higher
      temperatures from the internal elimination. The maximum rates of % mass loss
      became independent of initial OH radical concentration at 440-480 K.
      Experimentally, the maximum % mass loss occurred from 440 to 460 K (heating rate
      dependent). Activation energies derived from the kMC-simulated TGAs of H4S (26-29
      kcal/mol) agreed with experiment for sulfonated polyethylene (~31 kcal/mol). The
      simulations revealed that in this region, decomposition of radical HOSO2 became
      competitive to alpha-H abstraction by HOSO2, making OH the carrying radical for
      the reaction chain. The maximum rate of % mass loss for internal elimination was
      observed at temperatures >600 K. Low-scale carbonization utilizes temperatures
      <620 K; thus, internal elimination will not be competitive. E(i)5 elimination has
      been studied for sulfoxides and sulfones, but this represents the first study of
      internal elimination in sulfonic acids.

PMID- 23560685
TI  - Depression as a psychosocial consequence of occupational injury in the US working
      population: findings from the medical expenditure panel survey.
AB  - BACKGROUND: Empirical evidence describing the psychosocial consequences of
      occupational injury is still limited. The effect of occupational injury on
      depression might pose unique challenges in workers compared with other kinds of
      injury. This study aimed to assess the differential impact of workplace injury
      compared with non-workplace injury on depression over time, and to identify the
      potential risk factors associated with post-injury depression in the US working
      population. METHODS: Using pooled panel data from the Medical Expenditure Panel
      Survey 2000-2006, a total of 35,155 workers aged 18-64 years who had been
      followed for about 18 months in each panel were analyzed. Injuries in the 4-5
      months before baseline, and subsequent depression incidence during follow-up,
      were identified using ICD-9 codes for the medical conditions captured in personal
      interviews. A discrete time-proportional odds model was used. RESULTS: A total of
      5.5% of workers with occupational injury at baseline reported depression at
      follow-up, compared with 4.7% of workers with non-occupational injury and 3.1% of
      workers without injuries. Those with occupational injuries had more severe
      injuries and required longer treatment, compared with those with non-occupational
      injuries. Only 39% of workers with workplace injuries were paid Workers'
      Compensation (WC). The association between injury and depression appeared to be
      stronger for workplace injury, and the adjusted odds ratio for depression was
      1.72 for those with occupational injury (95% CI: 1.27-2.32), and 1.36 for those
      with non-occupational injury (95% CI: 1.07-1.65) compared with the no-injury
      group, after controlling for relevant covariates. Occupational injury was
      associated with higher odds of developing depression over time. WC as a source of
      medical payment was associated with 33% higher odds of developing depression (95%
      CI: 1.01-1.74). Part-time work, shorter job tenure, and long working hours were
      independently associated with post-injury depression risk. CONCLUSIONS: Workers
      with occupational injury were more likely to become depressed than those with non
      occupational injury. The psychosocial consequences of occupational injury,
      including depression, deserve further exploration to adequately support those
      injured at work. This finding also emphasizes a need for early intervention to
      reduce the burden of depression associated with occupational injury.

PMID- 23560687
TI  - The all-seeing needle instead of the Veress needle in pediatric urologic
      laparoscopy.
AB  - PURPOSE: To investigate the feasibility of the all-seeing needle for safe entry
      and creation of pneumoperitoneum in pediatric urologic laparoscopy. PATIENTS AND
      METHODS: A total of 14 children underwent various transperitoneal urologic
      laparoscopic procedures. The all-seeing needle, which is 4.85F in diameter, was
      used for safe entry into the abdominal cavity at the site of the umblicus in all
      cases. The microoptic was integrated with the light system and connected via a
      zoom ocular enabling direct visualization of the layers between the skin and the
      peritoneal cavity. Once the intraperitoneal access was obtained, CO2
      pneumoperitoneum was created from one port of the three-way connector attached to
      the proximal part of the needle. Then the laparoscopic trocars were placed under
      vision of the microoptical system. RESULTS: Mean age of the children was 4.5 +/-
      2.9 years. In all children, the all-seeing needle was safely introduced into the
      abdominal cavity under direct vision. Then, CO2 pneumoperitoneum was succesfully
      performed. The mean time for optical puncture was calculated as 1.1 +/- 0.8
      minutes. No complication was encountered during the introduction of the needle,
      creation of the pneumoperitoneum, and placement of the trocars. CONCLUSIONS: The
      all-seeing needle appears to be beneficial in safe entry and for creating
      pneumoperitoneum in laparoscopic pediatric urology cases. It eliminates the
      disadvantages of the Veress needle, which is blunt insertion, and may possibly
      prevent complications.

PMID- 23560688
TI  - On the valence of surprise.
AB  - While surprise is a common emotion in everyday life, some of its fundamental
      characteristics are still unclear. For example, what does surprise feel like,
      positive or negative? The emotion literature has been somewhat unclear about the
      experiential valence of surprise. Surprise has been depicted as a pre-affective
      state, or as an emotion that can be both positive and negative, depending on the
      goal conduciveness of the surprising event. Based on recent work on cognitive
      consistency and neuroscientific/psychophysiological studies on surprise, we
      explored the possibility that surprise may be a (mildly) negative emotion in a
      study of autobiographical recall of unexpected and surprising events (Experiment
      1) and in two studies of facial expressions of surprise (Experiments 2 and 3a/b).
      The studies show that experience of surprise and the perception of surprise in
      others may indeed be initially negative. We furthermore show how linguistic
      features of surprise and the temporal dynamics may have contributed to previous
      confusion regarding its valence. 

PMID- 23560690
TI  - Successful renal transplantation for end-stage renal insufficiency developed in a
      patient with Castleman's disease.

PMID- 23560689
TI  - Mycoleptodiscins A and B, cytotoxic alkaloids from the endophytic fungus
      Mycoleptodiscus sp. F0194.
AB  - Two novel reddish-orange alkaloids, mycoleptodiscin A (1) and mycoleptodiscin B
      (2), were isolated from liquid cultures of the endophytic fungus Mycoleptodiscus
      sp. that had been isolated from Desmotes incomparabilis in Panama. Elucidation of
      their structures was accomplished using 1D and 2D NMR spectroscopy in combination
      with IR spectroscopic and MS data. These compounds are indole-terpenes with a new
      skeleton uncommon in nature. Mycoleptodiscin B (2) was active in inhibiting the
      growth of cancer cell lines with IC50 values in the range 0.60-0.78 MUM. 

PMID- 23560691
TI  - Use of a self-curing resorbable polymer in vertical ridge augmentations - a pilot
      study in dogs.
AB  - AIM: The aim of the present study was to evaluate bone formation in vertical
      ridge augmentations using particulate bone grafting material stabilized by a
      resorbable polymer. MATERIAL AND METHODS: Three vertical defects were created in
      the maxillary alveolar ridge of six Beagle dogs 3 months after the removal of all
      premolars. One defect in each dog was filled with
      tricalciumphosphate/hydroxylapatite (TCP/HA) grafting material and stabilized
      using a poloxamer hydrogel (test group). Defects filled with grafting material
      only and covered with a collagen membrane as well as empty defects served as
      controls (controls 1 & 2). Bone formation in the defects was evaluated after 14
      weeks of healing using histomorphometry on undecalcified thick-section specimens.
      RESULTS: There was no difference between the test group and the controls with
      respect to the amount of newly formed bone, percentage of bone fill, and bone
      density. The mean maximum bone height within the augmented area was the only
      parameter that was significantly higher in the test group compared with empty
      defects. The use of the poloxamer gel did not result in a better preservation of
      ridge shape compared with the group of augmentations covered with a collagen
      membrane. CONCLUSIONS: The use of a poloxamer gel for the stabilization of
      particulate bone grafting material in vertical ridge augmentations had no
      advantage compared with coverage of grafting materials with a collagen membrane.

PMID- 23560692
TI  - Mitochondrial genome of the Alpine musk deer Moschus chrysogaster (Artiodactyla:
      Ruminantia: Moschidae).
AB  - The Alpine musk deer (Moschus chrysogaster) is an endangered species, which is
      distributed on the plateau and mountains, mainly in Neimenggu, Ningxia, Qinghai,
      Gansu, Sichuan, Tibet, Yunnan, Xinjiang, and other places. In this study, we
      determined the complete mitochondrial genome of M. chrysogaster. The circle
      genome was 16,354 bp and consists of 13 protein-coding genes, 22 transfer RNA
      genes, 2 ribosomal RNA genes and 1 control region (CR). The CR was located
      between the tRNA(Pro) and tRNA(Phe) genes and is 924 bp in length. Overall base
      composition of the complete mitochondrial DNA was 34.0% A, 28.0% T, 25.1% C, and
      12.9% G. The M. chrysogaster mitochondrial genome had 21 tRNA genes folded in the
      typical cloverleaf structure, with a unique exception of tRNA(Ser). 

PMID- 23560693
TI  - Suppressive effect of ascorbic acid on the mutagenesis induced by the bystander
      effect through mitochondrial function.
AB  - Here, we focused on suppressive effect of ascorbic acid (AsA) on changes in
      mitochondrial function and mutagenesis by the radiation- induced bystander effect
      (RIBE). In mammalian cell lines, medium transfer assay was performed and
      conditioned medium including secreted factors after X-irradiation were examined
      to detect the RIBE. We found that the membrane potential and increased levels of
      superoxide radical (O2(-)) in mitochondria were modulated in cells treated with
      conditioned medium from irradiated cells. The result of the present study also
      demonstrated that increases in reactive oxygen species (ROS) levels led to the
      induction of gene mutations. Interestingly, the modulations in mitochondria, in
      addition to mutation inductions by RIBE, were completely suppressed by treatment
      with AsA in cells treated with conditioned medium. These results suggest that
      mutagenesis, which may have resulted from secreted factors involving the RIBE,
      may be induced by ROS that are localized in mitochondria and may be relieved by
      AsA.

PMID- 23560694
TI  - Different motor learning effects on excitability changes of motor cortex in
      muscle contraction state.
AB  - We aimed to investigate whether motor learning induces different excitability
      changes in the human motor cortex (M1) between two different muscle contraction
      states (before voluntary contraction [static] or during voluntary contraction
      [dynamic]). For the same, using motor evoked potentials (MEPs) obtained by
      transcranial magnetic stimulation (TMS), we compared excitability changes during
      these two states after pinch-grip motor skill learning. The participants
      performed a force output tracking task by pinch grip on a computer screen. TMS
      was applied prior to the pinch grip (static) and after initiation of voluntary
      contraction (dynamic). MEPs of the following muscles were recorded: first dorsal
      interosseous (FDI), thenar muscle (Thenar), flexor carpi radialis (FCR), and
      extensor carpi radialis (ECR) muscles. During both the states, motor skill
      training led to significant improvement of motor performance. During the static
      state, MEPs of the FDI muscle were significantly facilitated after motor
      learning; however, during the dynamic state, MEPs of the FDI, Thenar, and FCR
      muscles were significantly decreased. Based on the results of this study, we
      concluded that excitability changes in the human M1 are differentially influenced
      during different voluntary contraction states (static and dynamic) after motor
      learning.

PMID- 23560696
TI  - Potential for development of haemophilia link nurse role within UK hospitals.
AB  - Link nurses are practising nurses with an expressed interest in a given
      specialty, with formal links to clinical nurse specialists and other specialist
      staff. The role involves attending meetings to discuss ideas and new
      developments, and relaying findings to other ward nurses to improve their
      practice. Such nurses are common in many specialties such as diabetes and tissue
      viability. In haemophilia, the role has the potential to enhance the care of
      haemophilia patients on general hospital wards. In April 2012, a focus group of
      five haemophilia nurses was convened to discuss their experiences of 'link nurse'
      programmes within district general hospitals and the potential value of
      developing the haemophilia link nurse role, and to consider the materials needed
      to support such role development. It was agreed to test whether other haemophilia
      nurses perceived such a need by means of a short five-item questionnaire devised
      by the group and made available to all members of the UK's Haemophilia Nurse's
      Association via Survey-Monkey. Final responses from 59 haemophilia nurses across
      the UK have been analysed. Most nurses agreed that there was value in the
      development of a haemophilia link nurse role within UK hospitals and thought
      their trusts would support it. While barriers and potential downsides were
      acknowledged, this was seen as a useful way of sharing information and knowledge
      with colleagues from different specialties and of raising awareness of bleeding
      disorders among the general nursing community. Haemophilia nurses should
      coordinate the development of a Haemophilia Link Nurse training and education
      pack.

PMID- 23560697
TI  - Challenges in tracing the fate and effects of atmospheric polycyclic aromatic
      hydrocarbon deposition in vascular plants.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic pollutants that
      raise environmental concerns because of their toxicity. Their accumulation in
      vascular plants conditions harmful consequences to human health because of their
      position in the food chain. Consequently, understanding how atmospheric PAHs are
      taken up in plant tissues is crucial for risk assessment. In this review we
      synthesize current knowledge about PAH atmospheric deposition, accumulation in
      both gymnosperms and angiosperms, mechanisms of transfer, and ecological and
      physiological effects. PAHs emitted in the atmosphere partition between gas and
      particulate phases and undergo atmospheric deposition on shoots and soil. Most
      PAH concentration data from vascular plant leaves suggest that contamination
      occurs by both direct (air-leaf) and indirect (air-soil-root) pathways.
      Experimental studies demonstrate that PAHs affect plant growth, interfering with
      plant carbon allocation and root symbioses. Photosynthesis remains the most
      studied physiological process affected by PAHs. Among scientific challenges,
      identifying specific physiological transfer mechanisms and improving the
      understanding of plant-symbiont interactions in relation to PAH pollution remain
      pivotal for both fundamental and applied environmental sciences.

PMID- 23560695
TI  - Diagnosis and management of non-alcoholic fatty liver disease and related
      metabolic disorders: consensus statement from the Study Group of Liver and
      Metabolism, Chinese Society of Endocrinology.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in
      Western countries, affecting 20%-33% of the general population. Large population
      based surveys in China indicate a prevalence of approximately 15%-30%. Worldwide,
      including in China, the prevalence of NAFLD has increased rapidly in parallel
      with regional trends of obesity, type 2 diabetes and metabolic syndrome. In
      addition, NAFLD has contributed significantly to increased overall, as well as
      cardiovascular and liver-related, mortality in the general population. In view of
      rapid advances in research into NAFLD in recent years, this consensus statement
      provides a brief update on the progress in the field and suggests preferred
      approaches for the comprehensive management of NAFLD and its related metabolic
      diseases.

PMID- 23560698
TI  - Procollagen Type I C-terminal propeptide, procollagen Type III N-terminal
      propeptide, hyaluronic acid, and laminin in the cerebrospinal fluid of rats with
      communicating hydrocephalus.
AB  - OBJECT: Fibrosis along the route of CSF flow is indicated by the development of
      hydrocephalus. The changes of fibrosis index might reflect the level of
      hydrocephalus and even become a diagnostic index of hydrocephalus. The object of
      this study was to analyze the levels of procollagen Type I C-terminal propeptide
      (PICP), procollagen Type III N-terminal propeptide (PIIINP), hyaluronic acid
      (HA), and laminin (LN) and their significance in the CSF of communicating
      hydrocephalus rat models. METHODS: Thirty adult Sprague-Dawley rats were randomly
      divided into 3 groups: hydrocephalus group (20 rats) with intraventricular kaolin
      injections, sham control group (5 rats) with saline injections, and normal group
      (5 rats) without any processing. The levels of PICP, PIIINP, HA, and LN in the
      CSF were detected using ELISA. RESULTS: Levels of PICP, PIIINP, HA, and LN in the
      hydrocephalus group were significantly higher than those in the saline control
      group (p < 0.05). It was revealed by correlation analysis that the increase was
      positively correlated with the severity of ventricular dilation. CONCLUSIONS:
      Results indicated that PICP, PIIINP, HA, and LN continue to rise dramatically in
      experimental hydrocephalus and may serve as the diagnostic index of
      hydrocephalus.

PMID- 23560700
TI  - Ruthenia-based electrochemical supercapacitors: insights from first-principles
      calculations.
AB  - Electrochemical supercapacitors (ECs) have important applications in areas
      wherethe need for fast charging rates and high energy density intersect,
      including in hybrid and electric vehicles, consumer electronics, solar cell based
      devices, and other technologies. In contrast to carbon-based supercapacitors,
      where energy is stored in the electrochemical double-layer at the
      electrode/electrolyte interface, ECs involve reversible faradaic ion
      intercalation into the electrode material. However, this intercalation does not
      lead to phase change. As a result, ECs can be charged and discharged for
      thousands of cycles without loss of capacity. ECs based on hydrous ruthenia,
      RuO2.xH2O, exhibit some of the highest specific capacitances attained in real
      devices. Although RuO2 is too expensive for widespread practical use, chemists
      have long used it as a model material for investigating the fundamental
      mechanisms of electrochemical supercapacitance and heterogeneous catalysis. In
      this Account, we discuss progress in first-principles density-functional theory
      (DFT) based studies of the electronic structure, thermodynamics, and kinetics of
      hydrous and anhydrous RuO2. We find that DFT correctly reproduces the metallic
      character of the RuO2 band structure. In addition, electron-proton double
      insertion into bulk RuO2 leads to the formation of a polar covalent O-H bond with
      a fractional increase of the Ru charge in delocalized d-band states by only 0.3
      electrons. This is in slight conflict with the common assumption of a Ru valence
      change from Ru(4+) to Ru(3+). Using the prototype electrostatic ground state
      (PEGS) search method, we predict a crystalline RuOOH compound with a formation
      energy of only 0.15 eV per proton. The calculated voltage for the onset of bulk
      proton insertion in the dilute limit is only 0.1 V with respect to the reversible
      hydrogen electrode (RHE), in reasonable agreement with the 0.4 V threshold for a
      large diffusion-limited contribution measured experimentally. DFT calculations
      also predict that proton diffusion in RuO2 is hindered by a migration barrier of
      0.8 eV, qualitatively explaining the observed strong charging rate-dependence of
      the diffusion-limited contribution. We found that reversible adsorption of up to
      1.5 protons per Ru on the (110) surface contributes to the measured capacitive
      current at higher voltages. PEGS-derived models of the crystal structure of
      hydrated ruthenia show that incorporation of water in Ru vacancies or in bulk
      crystals is energetically much more costly than segregation of water molecules
      between slabs of crystalline RuO2. These results lend support to the so-called
      "water at grain boundaries" model for the structure of hydrous RuO2.xH2O. This
      occurs where metallic nanocrystals of RuO2 are separated by grain boundary
      regions filled with water molecules. Chemists have attributed the superior charge
      storage properties of hydrous ruthenia to the resulting composite structure. This
      facilitates fast electronic transport through the metallic RuO2 nanocrystals and
      fast protonic transport through the regions of structural water at grain
      boundaries. 

PMID- 23560699
TI  - Agreement between photographic and clinical examinations in detecting
      developmental defects of enamel in infants.
AB  - OBJECTIVES: This study assesses the reliability of photographic method with
      clinical examinations in detecting developmental defects of enamel (DDE) in the
      anterior primary teeth of infants. METHODS: The study sample was a part of an
      ongoing longitudinal study to assess risk factors for early childhood caries, and
      consisted of 138 and 238 infants who had scheduled follow-up visits at
      approximately 8 and 18-20 months corrected age, respectively. The modified DDE
      Index was used to record enamel defects (opacity, hypoplasia, and all types of
      defects) on anterior primary teeth by trained dentist examiners. Photographs of
      the teeth were taken using a digital camera. Statistical analysis included
      Cohen's Kappa for reliability, and McNemar test and paired t-test for comparison
      between photographic and clinical examinations. RESULTS: The level of agreement
      between clinical and photographic methods was fair to moderate with Kappa values
      ranging from 0.252 to 0.514. The photographic examination detected significantly
      more DDE than the clinical examination regardless of age group and type of DDE.
      The intra- and inter-examiner reliability of the photographic method was
      excellent with Kappa values ranging from 0.638 to 0.927. CONCLUSIONS: Within the
      limitation of this study, the photographic method can be a sound approach for
      verifying the diagnosis of DDE.

PMID- 23560701
TI  - The influence of profession and therapy type on the treatment of sexual
      dysfunctions.
AB  - Sexual dysfunctions are serious mental health issues that affect an estimated 1
      in 3 Americans, yet many people with sexual dysfunctions do not seek treatment.
      Health services research on variables related to access, barriers, costs, and
      outcomes of treatment may help improve the quality of care. The current research
      is a retrospective analysis of administrative data from CIGNA that explores
      whether the type of profession (i.e., psychologist, social worker, marriage and
      family therapist, or professional counselor) or therapy modality (i.e.,
      individual, conjoint, or mixed-mode, a combination of individual and conjoint
      therapy) influence the outcomes of mental health treatment. Participants included
      230 men and 189 women between the ages of 18 to 101 years from all regions of the
      United States who received treatment for sexual disorders from 2001 to 2006.
      Results indicate that outcomes are similar across the different license types.
      Results also suggest that mixed-mode therapy has lower dropout rates and longer
      retention than individual or conjoint therapy. These results suggest that using a
      combination of relational and individual sessions may be beneficial for the
      treatment of sexual dysfunctions.

PMID- 23560702
TI  - Deuterium oxide dilution: a novel method to study apical water layers and
      transepithelial water transport.
AB  - Lung epithelia regulate the water flux between gas filled airways and the
      interstitial compartment in order to maintain organ function. Current methodology
      to assess transepithelial water transport is limited. We present a D2O dilution
      method to quantify submicroliter volumes of aqueous solutions on epithelial cell
      layers. Evaluating D2O/H2O mixtures using mid-infrared (2-25 MUm) attenuated
      total reflection (ATR) spectroscopy, with a resolution of 0.06% vol/vol change,
      corresponding to 24 nL, was achieved. Using this method, we demonstrate that
      water transport across NCI-H441 lung epithelial cell layers and apical surface
      liquid (ASL) volumes are coupled to dexamethasone dependent amiloride-sensitive
      ion transport. However, contrary to current dogma, electrogenic transport is not
      rate-limiting for water transport. This clearly indicates the need to directly
      assess net water rather than ion transport across epithelial cell layers. The
      presented D2O dilution method enables such direct and quick quantification of
      transepithelial water transport with high resolution.

PMID- 23560703
TI  - Automatic front-crawl temporal phase detection using adaptive filtering of
      inertial signals.
AB  - This study introduces a novel approach for automatic temporal phase detection and
      inter-arm coordination estimation in front-crawl swimming using inertial
      measurement units (IMUs). We examined the validity of our method by comparison
      against a video-based system. Three waterproofed IMUs (composed of 3D
      accelerometer, 3D gyroscope) were placed on both forearms and the sacrum of the
      swimmer. We used two underwater video cameras in side and frontal views as our
      reference system. Two independent operators performed the video analysis. To test
      our methodology, seven well-trained swimmers performed three 300 m trials in a 50
      m indoor pool. Each trial was in a different coordination mode quantified by the
      index of coordination. We detected different phases of the arm stroke by
      employing orientation estimation techniques and a new adaptive change detection
      algorithm on inertial signals. The difference of 0.2 +/- 3.9% between our
      estimation and video-based system in assessment of the index of coordination was
      comparable to experienced operators' difference (1.1 +/- 3.6%). The 95% limits of
      agreement of the difference between the two systems in estimation of the temporal
      phases were always less than 7.9% of the cycle duration. The inertial system
      offers an automatic easy-to-use system with timely feedback for the study of
      swimming.

PMID- 23560704
TI  - Prevalence of intestinal parasitic infections and risk factors among
      schoolchildren at the University of Gondar Community School, Northwest Ethiopia:
      a cross-sectional study.
AB  - BACKGROUND: Intestinal parasitic infections are among the major public health
      problems in Sub-Saharan Africa. Their distribution is mainly associated with poor
      personal hygiene, environmental sanitation and limited access to clean water.
      Indeed, epidemiological information on the prevalence of various intestinal
      parasitic infections in different localities is a prerequisite to develop
      appropriate control measures. Therefore, the aim of this study was to assess the
      prevalence of intestinal parasitic infections and associated risk factors among
      schoolchildren. METHOD: This school-based cross-sectional study was undertaken at
      the University of Gondar Community School from April 2012 to June 2012. Study
      subjects were selected using a systematic random sampling method. Data were
      gathered through direct interview by using a pretested questionnaire. The
      collected stool specimens were examined microscopically for the presence of eggs,
      cysts and trophozoites of intestinal parasites using direct saline smear and
      formol-ether concentration methods. Data entry and analysis were done using SPSS
      version 16 software. RESULT: Out of 304 study subjects, 104 (34.2%) were infected
      with one or more intestinal parasites. The prevalence rate was 43 (32.1%) for
      male and 61 (35.9%) for female. The prevalence of intestinal parasites was high
      in age group of 10-12 years compared to other age groups. The predominant
      intestinal parasite was Hymenolepis nana, followed by Entamoeba
      histolytica/dispar and Ascaris lumbricoides with 42 (13.8%), 28 (9.2%), 18
      (5.9%), respectively. Hand washing practice and ways of transportation were
      statistically associated with intestinal parasitic infections. Children in grades
      1 to 3 had a higher prevalence of intestinal helminthic infection than those in
      grades 4 to 8 (p = 0.031). CONCLUSIONS: Intestinal parasites were prevalent in
      varying magnitude among the schoolchildren. The prevalence of infections were
      higher for helminths compared to protozoa. Measures including education on
      personal hygiene, environmental sanitation, water supply and treatment should be
      taken into account to reduce the prevalence of intestinal parasites.

PMID- 23560706
TI  - Update on Kawasaki disease: epidemiology, aetiology and pathogenesis.
AB  - Kawasaki disease is an acute systemic vasculitis predominantly affecting young
      children. It is due to an abnormal host response to as yet unidentified
      infectious trigger(s). Kawasaki disease may cause coronary artery damage, long
      term cardiovascular morbidity and occasionally mortality, especially if the
      diagnosis is missed or timely treatment is not given. This is the first of two
      updates on Kawasaki disease. Here we review recent advances in epidemiology,
      possible aetiologies, host susceptibility and pathogenesis of this fascinating
      condition. 

PMID- 23560705
TI  - Non-linear association between 25-hydroxyvitamin D and the incidence of type 2
      diabetes: a community-based nested case-control study.
AB  - AIMS: To examine the nature of the association between 25-hydroxyvitamin D
      [25(OH)D] and newly diagnosed type 2 diabetes. METHODS: Serum 25(OH)D
      concentrations were measured for 761 participants (aged 20-83 years) in the
      Tehran Lipid and Glucose Study, selected for a 1-to-3 nested case-control study.
      Cases were 191 cases of Type 2 diabetes diagnosed during a median follow-up of
      3.6 years. A total of 570 participants were matched with these cases with regard
      to age, sex, BMI, and month of entering the study. Diabetes was defined according
      to the American Diabetes Association criteria, 2003. Serum 25(OH)D was measured
      using the enzyme immunoassay method. Odds ratios for Type 2 diabetes were
      obtained from conditional logistic regression models for tertiles of serum
      25(OH)D concentrations [tertile-1: 2.82-11.02 (reference), tertile-2: 11.03
      21.80, and tertile-3: >= 21.82 ng/ml]. The multivariate model was adjusted for
      age, sex, family history of diabetes, systolic blood pressure, triglyceride-to-
      HDL cholesterol ratio, waist-to-height ratio, lifestyle modification
      intervention, leisure time physical activity, and fasting plasma glucose at
      baseline. Non-linearity in the associations between baseline 25(OH)D and Type 2
      diabetes, was examined by using restricted cubic splines. RESULTS: Unadjusted
      odds ratios (95% confidence intervals) of diabetes were 0.73 (0.74-1.13), 0.54
      (0.34-0.85) for the second and third tertiles, respectively. Multivariate
      adjusted odds ratios were 0.47 (0.25-0.90) and 0.43 (0.23-0.82), respectively.
      Below the cutoff of ~ 10 ng/ml the risk of newly diagnosed Type 2 diabetes
      increased dramatically. DISCUSSION: It was found that 25(OH)D concentrations
      contributed to the Type 2 diabetes incidence rate in a non-linear fashion, with
      the risk beginning to increase sharply for values < 10 ng/ml.

PMID- 23560707
TI  - Thermodynamically stable vesicle formation and vesicle-to-micelle transition of
      single-tailed anionic surfactant in water.
AB  - The aggregation behavior of sodium 3,6,9,12,15-pentaoxa-heptacosanoate (AEC4-Na)
      in aqueous solution with increase of the concentration at 25  degrees C was
      investigated using differential scanning calorimetry, equilibrium surface
      tension, solubilization of an oil-soluble dye, steady-state fluorescence, dynamic
      light scattering, and freeze-fractured transmission electron microscopy. Vesicle
      formation of AEC4-Na preceded micelle formation below the critical micelle
      concentration (cmc). The vesicle-to-micelle transition was observed through a
      narrow concentration region above the cmc. The mean diameters of the vesicles and
      micelles were not affected by the concentration. All solutions over a wide range
      of concentrations were homogeneously transparent with a low Krafft point below 0 
      degrees C. These results indicate that the AEC4-Na vesicles have a
      thermodynamically stable structure. Vesicle formation may be caused by a
      pseudobinary mixed surfactant system composed of monomeric AEC4-Na and an acid
      soap that consists of a dimer complex formed between AEC4-Na and unneutralized
      AEC4-Na. The thermodynamic stability would then result from the inhibition of
      close intermolecular aggregation and flexibility of the molecular shape in the
      vesicles due to the oxyethylene units in AEC4-Na.

PMID- 23560708
TI  - Biomechanical evaluation of 2 insertion points for ventral screw fixation of C-2
      dens fractures.
AB  - OBJECT: For many type II fractures of the dens (Anderson and D'Alonzo
      classification), a double anterior screw fixation is performed. If screw
      disruption occurs, the location is most often at the anterior caudal endplate and
      body of the axis and not directly at the fracture line. The authors' objective
      was to determine the differences in primary mechanical stability at 2 insertion
      points used in ventral screw fixation of type II fractures of the C-2 dens.
      METHODS: Screw fixation was performed on 16 formalin-fixed human C-2 dens
      specimens. The specimens were divided into 2 groups. For group 1, the screws were
      inserted directly at the anterior lower endplates; for group 2, the screws were
      inserted 2 mm dorsal to the anterior wall of the vertebral body. After a type II
      odontoid fracture was created with an oscillating saw, screw fixation was
      performed using two 3.5-mm partially threaded lag screws with washers.
      Subsequently, each vertebral body was continuously loaded. The criterion for
      breakage was reversal of the force vector. RESULTS: In group 1, screw disruption
      occurred at the point of entry; the mean load failure was 290.5 +/- 106 N. In
      group 2, no screw disruption occurred; the mean load failure was 574.2 +/- 170.5
      N. These results were significant (p < 0.05). CONCLUSIONS: For double screw
      fixation of type II fractures of the dens (Anderson and D'Alonzo classification),
      placement of the screws as far dorsal to the anterior lower endplate as possible
      seems to favorably affect primary stability. In actual clinical practice, care
      should be taken to not damage the anterior wall of the vertebral body of the axis
      during screw insertion.

PMID- 23560709
TI  - Revision surgery after interbody fusion with rhBMP-2: a cautionary tale for spine
      surgeons.
AB  - Recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes the induction
      of bone growth and is widely used in spine surgery to enhance arthrodesis.
      Recombinant human BMP-2 has been associated with a variety of complications
      including ectopic bone formation, adjacent-level fusion, local bone resorption,
      osteolysis, and radiculitis. Some of the complications associated with rhBMP-2
      may be the result of rhBMP-2 induction of the inflammatory host response. In this
      paper the authors report on a patient with prior transforaminal lumbar interbody
      fusion (TLIF) using an interbody cage packed with rhBMP-2, in which rhBMP-2
      possibly contributed to vascular injury during an attempted anterior lumbar
      interbody fusion. This 63-year-old man presented with a 1-year history of
      worsening refractory low-back pain and radiculopathy caused by a Grade 1
      spondylolisthesis at L4-5. He underwent an uncomplicated L4-5 TLIF using an rhBMP
      2-packed interbody cage. Postoperatively, he experienced marginal improvement of
      his symptoms. Within the next year and a half the patient returned with
      unremitting low-back pain and neurogenic claudication that failed to respond to
      conservative measures. Radiological imaging of the patient revealed screw
      loosening and pseudarthrosis. He underwent an anterior retroperitoneal approach
      with a plan for removal of the previous cage, complete discectomy, and placement
      of a femoral ring. During the retroperitoneal approach the iliac vein was adhered
      with scarring and fibrosis to the underlying previously operated L4-5 interbody
      space. During mobilization the left iliac vein was torn, resulting in significant
      blood loss and cardiac arrest requiring chest compression, defibrillator shocks,
      and blood transfusion. The patient was stabilized, the operation was terminated,
      and he was transferred to the intensive care unit. He recovered over the next
      several days and was discharged at his neurological baseline. The authors propose
      that the rhBMP-2-induced host inflammatory response partially contributed to
      vessel fibrosis and scarring, resulting in the life-threatening vascular injury
      during the reoperation. Spine surgeons should be aware of this potential
      inflammatory fibrosis in addition to other reported complications related to
      rhBMP-2.

PMID- 23560710
TI  - Long-term clinical results of microsurgical transdural discectomy with
      laminoplasty: follow-up results over 10 years.
AB  - OBJECT: In this retrospective analysis the authors describe the long-term
      clinical results of microsurgical transdural discectomy with laminoplasty (MTDL)
      in patients with cervical disc herniation (CDH). METHODS: Thirty patients (21
      males, 9 females; mean age at surgery 55 years) with CDH had surgical treatments
      consisting of MTDL between 1990 and 1998. All patients demonstrated signs or
      symptoms of cervical myelopathy and/or radiculomyelopathy. Clinical outcomes were
      evaluated by the Japanese Orthopaedic Association (JOA) scoring system and by
      recovery rate (RR). The degenerative grades of the intervertebral discs were also
      evaluated based on preoperative, postoperative, and final follow-up MR images.
      The average follow-up period was 14.1 years (range 10-22 years). RESULTS: Twenty
      (67%) of the 30 patients completed the follow-up in this study. The preoperative
      JOA scores in these patients averaged 11.8, and the postoperative scores at the
      final follow-up averaged 15.5 (average RR 69.6%). None of these patients required
      reoperation after MTDL. Although disc degeneration progressed during the follow
      up period, there were no cases of clinical deterioration, recurrence of disc
      herniation, or postoperative kyphotic deformity. CONCLUSIONS: Sufficient clinical
      results were obtained after the MTDL for a long-term follow-up period exceeding
      10 years. The MTDL may be an option for an alternative procedure if the patients
      are correctly selected and the procedure is safely performed.

PMID- 23560711
TI  - Relationship between degree of focal kyphosis correction and neurological
      outcomes for patients undergoing cervical deformity correction surgery.
AB  - OBJECT: Reversal of the normal cervical spine curvature, as seen in cervical
      kyphosis, can lead to mechanical pain, neurological dysfunction, and functional
      disabilities. Surgical intervention is warranted in patients with sufficiently
      symptomatic deformities in an attempt to correct the deformed cervical spine. In
      theory, improved outcomes should accompany a greater degree of correction toward
      lordosis, although there are few data available to test this relationship. The
      purpose of this study is to determine if the degree of deformity correction
      correlates with improvement in neurological symptoms following surgery for
      cervical kyphotic deformity. METHODS: A retrospective review of 36 patients with
      myelopathic symptoms who underwent cervical deformity correction surgery between
      2001 and 2009 was performed. Preoperative and postoperative radiographic findings
      related to the degree of kyphosis were collected and compared with functional
      outcome measures. The minimum follow-up time was 2 years. RESULTS: A significant
      relationship was observed between a greater degree of focal kyphosis correction
      and improved neurological outcomes according to the modified Japanese Orthopaedic
      Association (mJOA) score (r = -0.46, p = 0.032). For patients with severe
      neurological symptoms (mJOA score < 12) a trend toward improved outcomes with
      greater global kyphosis correction was observed (r = -0.56, p = 0.057). Patients
      with an mJOA score less than 16 who attained lordosis postoperatively had a
      significantly greater improvement in total mJOA score than patients who
      maintained a kyphotic position (achieved lordosis: 2.7 +/- 2.0 vs maintained
      kyphosis: 1.1 +/- 2.1, p = 0.044). CONCLUSIONS: The authors' results suggest that
      the degree of correction of focal kyphosis deformity correlates with improved
      neurological outcomes. The authors also saw a positive relationship between
      attainment of global lordosis and improved mJOA scores. With consideration for
      the risks involved in correction surgery, this information can be used to help
      guide surgical strategy decision making.

PMID- 23560712
TI  - Safety of spinal decompression using an ultrasonic bone curette compared with a
      high-speed drill: outcomes in 337 patients.
AB  - OBJECT: Unintended durotomies are a common complication of spine surgery and are
      often correlated with increased postoperative morbidity. Recently, ultrasonic
      bone curettes have been introduced in spine surgery as a possible alternative to
      the conventional high-speed drill, offering the potential for greater bone
      cutting precision and less damage to surrounding soft tissues. To date, however,
      few studies have investigated the safety and efficacy of the ultrasonic bone
      curette in reducing the rates of incidental durotomy compared with the high-speed
      drill. METHODS: The authors retrospectively reviewed the records of 337
      consecutive patients who underwent posterior cervical or thoracic decompression
      at a single institution between January 2009 and September 2011. Preoperative
      pathologies, the location and extent of spinal decompression, and the use of an
      ultrasonic bone curette versus the high-speed drill were noted. The rates of
      incidental durotomy, as well as hospital length of stay (LOS) and perioperative
      outcomes, were compared between patients who were treated using the ultrasonic
      bone curette and those treated using a high-speed drill. RESULTS: Among 88
      patients who were treated using an ultrasonic bone curette and 249 who were
      treated using a high-speed drill, 5 (5.7%) and 9 (3.6%) patients had an
      unintentional durotomy, respectively. This finding was not statistically
      significant (p = 0.40). No patients in either cohort experienced statistically
      higher rates of perioperative complications, although patients treated using an
      ultrasonic bone curette tended to have a longer hospital LOS. This difference may
      be attributed to the fact that this series contained a statistically higher
      number of metastatic tumor cases (p < 0.0001) in the ultrasonic bone curette
      cohort, likely increasing the LOS for that patient population. In 13 patients,
      the dural defect was repaired intraoperatively. No patients who experienced an
      incidental durotomy had new-onset or permanent neurological deficits
      postoperatively. CONCLUSIONS: The safety and efficacy of ultrasonic bone curettes
      in spine surgery has not been well established. This study shows that the
      ultrasonic bone curette has a similar safety profile compared with the high-speed
      drill, although both are capable of causing iatrogenic dural tears during spine
      surgery.

PMID- 23560713
TI  - Minimally invasive pedicle screw fixation combined with percutaneous
      vertebroplasty in the surgical treatment of thoracolumbar osteoporosis fracture.
AB  - OBJECT: The purpose of this study was to evaluate the feasibility and safety of
      minimally invasive pedicle screw fixation combined with percutaneous
      vertebroplasty (PVP) for treating acute thoracolumbar osteoporotic vertebral
      compression fracture (VCF) and preventing secondary VCF after PVP. METHODS:
      Twenty patients with a mean age of 73.6 years (range 65-85 years) who sustained
      fresh thoracic or lumbar osteoporotic VCFs without neurological deficits
      underwent minimally invasive pedicle screw fixation combined with PVP. Visual
      analog scale pain scores were recorded, and the Cobb angles and the central and
      anterior vertebral body (VB) heights were measured on the lateral radiographs
      before surgery and immediately, 1 month, 2 months, 3 months, 6 months, 1 year,
      and 2 years after surgery. RESULTS: The patients were followed up for an average
      of 26 months (range 24-30 months) after sugery. The visual analog scale score was
      found to be significantly decreased; from 7.3 +/- 1.3 before surgery to 1.2 +/-
      0.7 immediately after surgery and to 0.7 +/- 0.7 (p < 0.001) at the end of follow
      up. The Cobb angle was 17.0 degrees  +/- 4.3 degrees  before surgery and 6.4
      degrees  +/- 3.6 degrees  immediately after surgery. The central VB height that
      was 44.5% +/- 7.6% before surgery increased to 74.6% +/- 6.4% of the estimated
      intact central height immediately after surgery (p < 0.001). The anterior VB
      height increased from 50.7% +/- 7.4% before surgery to 82.5% +/- 6.7% of the
      estimated intact anterior height immediately after surgery (p < 0.001). There
      were no significant changes in the results obtained over the follow-up time
      period. There was no occurrence of new fracture in surgically treated or adjacent
      vertebrae in these patients. CONCLUSIONS: Minimally invasive pedicle screw
      fixation combined with PVP is a good choice for the treatment of acute
      thoracolumbar osteoporotic VCF and can prevent the occurrence of new VCFs after
      PVP.

PMID- 23560714
TI  - Citrus leaf blotch virus invades meristematic regions in Nicotiana benthamiana
      and citrus.
AB  - To invade systemically host plants, viruses need to replicate in the infected
      cells, spread to neighbouring cells through plasmodesmata and move to distal
      parts of the plant via sieve tubes to start new infection foci. To monitor the
      infection of Nicotiana benthamiana plants by Citrus leaf blotch virus (CLBV),
      leaves were agroinoculated with an infectious cDNA clone of the CLBV genomic RNA
      expressing green fluorescent protein (GFP) under the transcriptional control of a
      duplicate promoter of the coat protein subgenomic RNA. Fluorescent spots first
      appeared in agroinfiltrated leaves 11-12 days after infiltration, indicating CLBV
      replication. Then, after entering the phloem vascular system, CLBV was unloaded
      in the upper parts of the plant and invaded all tissues, including flower organs
      and meristems. GFP fluorescence was not visible in citrus plants infected with
      CLBV-GFP. Therefore, to detect CLBV in meristematic regions, Mexican lime (Citrus
      aurantifolia) plants were graft inoculated with CLBV, with Citrus tristeza virus
      (CTV), a virus readily eliminated by shoot-tip grafting in vitro, or with both
      simultaneously. Although CLBV was detected by hybridization and real-time reverse
      transcription-polymerase chain reaction (RT-PCR) in 0.2-mm shoot tips in all CLBV
      inoculated plants, CTV was not detected. These results explain the difficulty in
      eliminating CLBV by shoot-tip grafting in vitro. 

PMID- 23560715
TI  - Pyrosequencing of environmental soil samples reveals biodiversity of the
      Phytophthora resident community in chestnut forests.
AB  - Pyrosequencing analysis was performed on soils from Italian chestnut groves to
      evaluate the diversity of the resident Phytophthora community. Sequences analysed
      with a custom database discriminated 15 pathogenic Phytophthoras including
      species common to chestnut soils, while a total of nine species were detected
      with baiting. The two sites studied differed in Phytophthora diversity and the
      presence of specific taxa responded to specific ecological traits of the sites.
      Furthermore, some species not previously recorded were represented by a discrete
      number of reads; among these species, Phytophthora ramorum was detected at both
      sites. Pyrosequencing was demonstrated to be a very sensitive technique to
      describe the Phytophthora community in soil and was able to detect species not
      easy to be isolated from soil with standard baiting techniques. In particular,
      pyrosequencing is an highly efficient tool for investigating the colonization of
      new environments by alien species, and for ecological and adaptive studies
      coupled with biological detection methods. This study represents the first
      application of pyrosequencing for describing Phytophthoras in environmental soil
      samples. 

PMID- 23560716
TI  - Functional requirements for bacteriophage growth: gene essentiality and
      expression in mycobacteriophage Giles.
AB  - Bacteriophages represent a majority of all life forms, and the vast, dynamic
      population with early origins is reflected in their enormous genetic diversity. A
      large number of bacteriophage genomes have been sequenced. They are replete with
      novel genes without known relatives. We know little about their functions, which
      genes are required for lytic growth, and how they are expressed. Furthermore, the
      diversity is such that even genes with required functions - such as virion
      proteins and repressors - cannot always be recognized. Here we describe a
      functional genomic dissection of mycobacteriophage Giles, in which the virion
      proteins are identified, genes required for lytic growth are determined, the
      repressor is identified, and the transcription patterns determined. We find that
      although all of the predicted phage genes are expressed either in lysogeny or in
      lytic growth, 45% of the predicted genes are non-essential for lytic growth. We
      also describe genes required for DNA replication, show that recombination is
      required for lytic growth, and that Giles encodes a novel repressor. RNAseq
      analysis reveals abundant expression of a small non-coding RNA in a lysogen and
      in late lytic growth, although it is non-essential for lytic growth and does not
      alter lysogeny.

PMID- 23560717
TI  - Conformational fluctuations of UreG, an intrinsically disordered enzyme.
AB  - UreG proteins are small GTP binding (G) proteins that catalyze the hydrolysis of
      GTP necessary for the maturation of urease, a virulence factor in bacterial
      pathogenesis. UreG proteins are the first documented cases of intrinsically
      disordered enzymes. The comprehension of the dynamics of folding-unfolding events
      occurring in this protein could shed light on the enzymatic mechanism of UreG.
      Here, we used the recently developed replica exchange with solute tempering
      (REST2) computational methodology to explore the conformational space of UreG
      from Helicobacter pylori (HpUreG) and to identify its structural fluctuations.
      The same simulation and analysis protocol has been applied to HypB from
      Methanocaldococcus jannaschii (MjHypB), which is closely related to UreG in both
      sequence and function, even though it is not intrinsically disordered. A
      comparison of the two systems reveals that both HpUreG and MjHypB feature a
      substantial rigidity of the protein regions involved in catalysis, justifying its
      residual catalytic activity. On the other hand, HpUreG tends to unfold more than
      MjHypB in portions involved in protein-protein interactions with
      metallochaperones necessary for the formation of multiprotein complexes known to
      be involved in urease activation.

PMID- 23560718
TI  - Molecular basis of two novel and related high-prevalence antigens in the Kell
      blood group system, KUCI and KANT, and their serologic and spatial association
      with K11 and KETI.
AB  - BACKGROUND: The numerous antigens in the Kell blood group system result from
      missense nucleotide changes in KEL. Antibodies to antigens in this system can be
      clinically important. We describe six probands whose plasma contained antibodies
      to high-prevalence Kell antigens and discuss their relationship. STUDY DESIGN AND
      METHODS: Polymerase chain reaction amplification, direct sequencing, restriction
      fragment length polymorphism assays, hemagglutination, flow cytometry, and
      protein modeling were performed by standard methods. RESULTS: Proband 1 (KUCI)
      and her serologically compatible sister were heterozygous for a nucleotide change
      in Exon 11 (KEL*1271C/T; Ala424Val). Proband 2 (KANT) was heterozygous for
      KEL*1283G/T (Arg428Leu) and KEL*1216C/T (Arg406Stop) in Exon 11. Red blood cells
      (RBCs) from Proband 1 and her sister were not agglutinated by plasma from Proband
      2; however, RBCs from Proband 2 were agglutinated by plasma from Proband 1.
      Probands 3, 4, 5, and 6 had the KEL*1391C>T change associated with the previously
      reported KETI- phenotype. Proband 5 was also homozygous for KEL*905T>C encoding
      the K11-K17+ phenotype. Hemagglutination studies revealed an association between
      KUCI, KANT, KETI, and K11. Protein modeling indicated that whereas Ala424 and
      Arg428 are clustered, Val302 and Thr464 are not. CONCLUSION: Ala424 in the Kell
      glycoprotein is associated with the high-prevalence Kell antigen, KUCI (ISBT
      006032), which is detected by the antibody of Proband 1. Arg428 is associated
      with the high-prevalence Kell antigen, KANT (ISBT 006033). The association
      between KUCI, KANT, KETI, and K11 and the results of protein modeling are
      discussed.

PMID- 23560719
TI  - Dental follicle progenitor cells responses to Porphyromonas gingivalis LPS.
AB  - Periodontitis is a bacterially induced chronic inflammatory disease. Dental
      follicle progenitor cells (DFPCs) have been proposed as biological graft for
      periodontal regenerative therapies. The potential impact of bacterial toxins on
      DFPCs properties is still poorly understood. The aim of this study was to
      investigate whether DFPCs are able to sense and respond to lipopolysaccharide
      (LPS) from Porphyromonas gingivalis, a major periopathogenic bacterium.
      Specifically, we hypothesized that LPS could influence the migratory capacity and
      IL-6 secretion of DFPCs. DFPCs properties were compared to bone marrow
      mesenchymal stem cells (BMSCs), a well-studied class of adult stem cells. The
      analysis by flow cytometry indicated that DFPCs, similar to BMSCs, expressed low
      levels of both toll-like receptor (TLR) 2 and 4. The TLR4 mRNA expression was
      down-regulated in response to LPS in both cell populations, while on protein
      level TLR4 was significantly up-regulated on BMSCs. The TLR2 expression was not
      influenced by the LPS treatment in both DFPCs and BMSCs. The migratory efficacy
      of LPS-treated DFPCs was evaluated by in vitro scratch wound assays and found to
      be significantly increased. Furthermore, we assayed the secretion of interleukin
      6 (IL-6), a potent stimulator of cell migration. Interestingly, the levels of IL
      6 secretion of DFPCs and BMSCs remained unchanged after the LPS treatment. Taken
      together, these results suggest that DFPCs are able to sense and respond to P.
      gingivalis LPS. Our study provides new insights into understanding the
      physiological role of dental-derived progenitor cells in sites of periodontal
      infection.

PMID- 23560720
TI  - Tranexamic acid without prophylactic factor replacement for prevention of
      bleeding in hereditary bleeding disorder patients undergoing endoscopy: a pilot
      study.
AB  - The risk of bleeding in patients with hereditary bleeding disorders (HBD)
      undergoing gastro-intestinal (GI) endoscopic procedures is unknown but guidelines
      generally recommend correction of factor deficiency. Investigate the safety of
      oral tranexamic acid (TA) without prophylactic factor replacement to prevent
      bleeding complications in patients with HBD undergoing elective GI endoscopic
      procedures. A prospective single-arm pilot study testing the feasibility of using
      TA, without prophylactic factor replacement or desmopressin preprocedure, for
      prevention of bleeding complications following elective standard risk (<1% risk
      of bleeding) endoscopic procedures in patients with HBD. Baseline factor levels,
      haemoglobin and iron studies (IS) were measured preprocedure. Primary outcome of
      bleeding (NCI CTCAE v3.0 Bleeding Scale) was undertaken by patient review and
      repeat Hb, IS on day 21. Twenty-eight patients underwent 32 GI endoscopic
      procedures from September 2010 until June 2012. The median age was 53 years
      (range 24-75 years) and disease types included mild haemophilia A/B (n = 12),
      severe haemophilia A/B (n = 9), von Willebrand disease (n = 5), FXI deficiency (n
      = 1) and FVII deficiency (n = 1). Procedures performed included 11 gastroscopies,
      12 colonoscopies, 8 gastroscopies and colonoscopies and 1 flexible sigmoidoscopy.
      Fourteen standard risk procedures and two high risk procedures were performed.
      Two patients experienced Grade 1 bleeding and one patient experienced Grade 2
      bleeding. This study suggests that TA without prophylactic factor replacement may
      be a safe approach for mild and moderate HBD patients undergoing standard risk
      endoscopic procedures, particularly where no biopsy is performed. These findings
      should be confirmed in a larger study.

PMID- 23560721
TI  - Claulansine F suppresses apoptosis induced by sodium nitroprusside in PC12 cells.
AB  - Reactive oxygen species (ROS) are known to be involved in many neurodegenerative
      diseases. This study assessed the effect of Claulansine F, a new carbazole
      isolated from Clausena lansium, on sodium nitroprusside (SNP)-treated rat
      pheochromocytoma PC12 cells. First, it was found that Claulansine F showed more
      potential on inhibiting the programmed death of PC12 cells than edaravone by cell
      viability, morphologic observation, and flow cytometric analysis. Further results
      also showed that Claulansine F attenuated the production of total intracellular
      ROS formation and lipid peroxidation in PC12 cells, inhibited the mitochondrial
      membrane potential (MMP) loss, and prevented the programmed cell death event via
      the P53/Bcl-2 family pathway. Its protective effect was likely medicated by the
      hydroxyl radical (.OH) scavenging ability, as it appeared to be not involved in
      the natural antioxidant system. These results suggested a promising potential for
      Claulansine F as a ROS scavenger in pathologies, where an oxidative stress is
      involved.

PMID- 23560722
TI  - Predictive QSAR models development and validation for human ether-a-go-go related
      gene (hERG) blockers using newer tools.
AB  - In the present computational analysis, pharmacophore-based active conformer
      selection method was used to derive active conformers for the physicochemical
      descriptors calculation. The significant regression models were validated using
      different validation methods, which provided significant Q(2) values. The
      distance-based approaches were also used to analyze the discriminant property of
      the molecules contributed in the models. The Mahalanobis distance (MD) values
      obtained from these studies revealed that the compounds with very high and very
      low acting human ether-a-go-go-related gene blockers possessed high MD values,
      while the predicted activity of those compounds exhibited less residual errors.
      The results obtained in the studies suggest that the distance-based approaches
      can be used to validate the quantitative structure-activity relationship models
      significantly. The descriptors contributed in the models explain that the
      flexibility of the bonds connected to the aromatic rings or non-polar region of
      the molecules make pi-pi interaction with the aromatic residues of the protein.

PMID- 23560723
TI  - Implant treatment choice after extraction of a vertically fractured tooth. A
      proposal for a clinical classification of bony defects based on a systematic
      review of literature.
AB  - OBJECTIVES: The objectives of this study were to propose a classification for the
      bone defects resulting after extraction of a vertically fractured tooth and to
      review the existing literature about the treatment of such kind of defects by
      means of dental implants in combination with regenerative procedures. MATERIALS
      AND METHODS: An electronic search was performed on biomedical databases using a
      combination of appropriated search terms combined through the use of Boolean
      operators. All articles concerning the treatment of peri-implant bone dehiscences
      and fenestrations through guided bone regeneration (GBR) with at least 6 months
      follow-up were eligible. Outcomes data extracted from the selected articles were
      summarized using descriptive tables. A classification of the bone defects
      associated with vertical root fracture (VRF) was also proposed. RESULTS: A total
      of 33 articles were included in the review. Twenty-three articles (814 implants)
      were about bone dehiscence treatment, ten articles presented the treatment of
      fenestrations, and ten (429 implants) adopted vertical bone augmentation. The
      percentage of bone filling was variable among different procedures and defect
      classification. The use of resorbable membrane was associated with better
      outcomes than the use of non-resorbable ones. CONCLUSIONS: Guided bone
      regeneration for the management of bone defects in the presence of a VRF of the
      extracted tooth is a viable treatment option. The assessment of bone defect
      geometry prior to a tooth extraction could be clinically relevant for evaluating
      the feasibility and the success of immediate implant placement as well as the
      need of GBR.

PMID- 23560724
TI  - An infant with acute brucellosis presenting with Coombs-positive autoimmune
      hemolytic anemia: is breastfeeding guilty for transmission?
AB  - Brucellosis is a zoonotic infectious disease that can be transmitted to humans
      through infected milk and dairy products. There are limited cases with Brucella
      infection acquired via breastfeeding in infants in the literature. Also, Coombs
      positive autoimmune hemolytic anemia as a result of the disease is comparatively
      rare when considering the other frequent hematologic complications. We report a
      mother who acquired the infection as a result of consuming infected milk and
      dairy products after delivery and of her 5-month-old baby, who had acquired the
      disease via breastfeeding and presented with Coombs-positive autoimmune hemolytic
      anemia.

PMID- 23560725
TI  - Asymmetric one-pot sequential Mannich/hydroamination reaction by organo- and gold
      catalysts: synthesis of spiro[pyrrolidin-3,2'-oxindole] derivatives.
AB  - An asymmetric organo- and gold-catalyzed one-pot sequential
      Mannich/hydroamination reaction has been developed. Using this protocol,
      spiro[pyrrolidin-3,2'-oxindole] derivatives were synthesized in good yields (up
      to 91%) and excellent enantioselectivities (up to 97% ee).

PMID- 23560726
TI  - The inverse relation of CA-125 to diabetes, metabolic syndrome, and associated
      clinical variables.
AB  - OBJECTIVE: We aimed to evaluate the association of carbohydrate antigen 125 (CA
      125; also known as cancer antigen 125) with various anthropometric and metabolic
      measures and also with diabetes and metabolic syndrome. METHODS: A total of 357
      diabetic and nondiabetic subjects were enrolled. CA-125, anthropometric
      parameters, lipids, blood pressure, as well as glycemic and insulin resistance
      measures were assessed. Metabolic syndrome was defined according to the
      International Diabetes Federation (IDF) criteria. RESULTS: CA-125 was lower in
      subjects with diabetes and/or metabolic syndrome [median (interquartile range) of
      8.20 (5.70-11.57) and 9.55 (6.50-16.25) U/mL for diabetic and nondiabetic
      subjects, respectively, P<0.05; 8.11 (5.90-11.45) and 9.50 (6.34-14.76) U/mL for
      subjects with metabolic syndrome and those without metabolic syndrome,
      respectively, P<0.05]. Anthropometric measures, dyslipidemia, insulin resistance,
      and blood pressure were inversely associated with CA-125 (P<0.05); waist
      circumference and body mass index were also identified as the strongest
      determinants of CA-125 (P<0.001). Using multiple linear regression models, waist
      circumference (beta=-0.088, P<0.01), apolipoprotein B (beta=-0.027, P<0.05), and
      systolic blood pressure (beta=-0.054, P<0.05) were independently associated with
      CA-125. However, none of insulin resistance measures remained in the model after
      adjusting for other clinical variables. CONCLUSION: CA-125 is inversely
      correlated with diabetes status, metabolic syndrome, and their associated
      anthropometric and metabolic measures. Furthermore, CA-125 is independently
      associated with waist circumference, apolipoprotein B, and systolic blood
      pressure, but not with any insulin resistance measures.

PMID- 23560728
TI  - Status of research on vitamin D supplementation in treating or preventing liver
      fibrosis.

PMID- 23560727
TI  - Reflux episodes detected by impedance in patients on and off esomeprazole: a
      randomised double-blinded placebo-controlled crossover study.
AB  - BACKGROUND: Combined with 24-h pH monitoring, the use of impedance is the most
      sensitive method available for detecting oesophageal reflux. Normal values for
      impedance have been previously established in healthy controls studied on and off
      proton pump inhibitors (PPI). AIMS: To determine the effects of PPIs on the total
      number of reflux episodes in the distal oesophagus measured by impedance in
      patients with and without gastro-oesophageal reflux disease (GERD). METHODS: In
      this prospective randomised double-blinded placebo controlled crossover study,
      all patients underwent two 24-h pH with impedance studies at least 2 weeks apart.
      Based on a randomisation scheme, patients received either 40 mg of esomeprazole
      twice daily for 1 week or identical capsule placebo for 1 week, then all patients
      were crossed over to the other treatment arm. GERD was defined by the validated
      Johnson-DeMeester score. Reflux by impedance was defined as a 50% decrease from
      baseline in retrograde movement of liquid between two impedance sites. RESULTS:
      Sixty-three patients were enrolled and 41 patients completed the study [mean age
      52 +/- 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African
      American]. Overall, there was no significant decrease in the total number of
      distal impedance episodes with esomeprazole compared with placebo (mean change
      6.1 +/- 22, P = 0.100). When analysed separately by GERD status, among GERD
      positive patients, there was a significant decrease in distal impedance episodes
      while on esomeprazole compared with placebo (mean change -16 +/- 22, P = 0.023),
      but not in GERD-negative patients (mean change -0.35 +/- 20, P = 0.872).
      CONCLUSION: Esomeprazole decreases significantly the number of reflux episodes
      detected by impedance, but only in patients with GERD.

PMID- 23560729
TI  - Emergency room visits for dental problems among working poor Canadians.
AB  - OBJECTIVES: To explore the risk of visiting hospital emergency rooms (ERs) for
      dental problems not associated with trauma among a sample of working poor
      Canadians. METHODS: Data stem from a telephone survey administered between March
      and August 2007 of working poor Canadians aged 18-64 years. Logistic regressions
      were employed to determine the predictors of reporting a visit to an ER for
      dental problems not associated with trauma. RESULTS: Approximately 6.1 percent of
      the sample reported visiting an ER in the past for a dental problem not
      associated with trauma. Those who were publicly insured, reported poor oral
      health, experienced a bed day due to dental pain, had dependent children, were
      lone parents, had competing needs, a history of receiving welfare, a history of
      an inability to afford dental care, and a perceived need for dental treatment
      were all more likely to have reported an ER visit. When adjusting for all
      variables, having experienced a bed day due to dental pain and a history of an
      inability to afford dental care were the dominant predictors of this outcome. A
      higher but not significantly different prevalence of ER visits for dental
      problems was found among the working poor sample when compared with the general
      Canadian population (6.1 percent versus 5.4 percent, P > 0.05). CONCLUSIONS:
      Further research is needed in order to provide insight into the reasons why the
      working poor population is seeking dental care in hospital settings.

PMID- 23560730
TI  - Cu2Ge(S(3-x)Se(x)) colloidal nanocrystals: synthesis, characterization, and
      composition-dependent band gap engineering.
AB  - A facile solution-phase route was developed to synthesize a family of
      monodisperse Cu2Ge(S(3-x)Se(x)) alloyed nanocrystals (NCs) with controlled
      composition across the entire range (0 <= x <= 3). The band gaps of the resultant
      NCs can be engineered by tuning the compositions with a nearly linear
      relationship between them. The band structures of the NCs were studied by cyclic
      voltammetry and UV-vis absorption spectroscopy. The conducting behavior was
      revealed to be p-type for these NCs by photoelectrochemical measurements. Their
      photovoltaic applicability was finally assessed by fabricating solar cells with
      the Cu2Ge(S2Se) NCs as light harvester and CdS nanorods as electron conducting
      materials.

PMID- 23560731
TI  - Polymerase chain reaction as the sole diagnostic tool for sacral-spinal
      tuberculosis.

PMID- 23560733
TI  - Three-dimensional anal ultrasound appearance of an ischiorectal abscess.

PMID- 23560732
TI  - Intracolonic vancomycin for severe Clostridium difficile colitis.
AB  - BACKGROUND: Clostridium difficile colitis is associated with increased age,
      antibiotic usage, and hospitalization. Severe C. difficile colitis refractory to
      medical therapy may require surgical intervention including subtotal colectomy.
      We initiated an adjuvant intracolonic vancomycin (ICV) enema protocol for
      inpatients with severe C. difficile colitis and compared the response to this
      therapy in patients from the community and nursing homes. METHODS: A single
      hospital, retrospective chart review was done on 47 consecutive patients with C.
      difficile colitis treated with ICV (1 g/500 mL normal saline q6h) from January
      2007 through October 2009. The proportions of patients with the outcomes of
      response to the ICV protocol, need for subtotal colectomy, and death were
      described. Associations of patient characteristics with these outcomes were
      examined with bivariate tests and multivariable logistic models with adjustment
      for age, hypoalbuminemia, acidosis, and nursing-home status. RESULTS: Thirty
      three of 47 patients (70%) with severe C. difficile colitis responded to adjunct
      ICV with complete resolution without surgery. Incomplete responders who had
      surgery were more likely to survive than those patients who did not undergo
      subtotal colectomy (p<0.01). Seven of nine patients who underwent surgery
      survived >90 d, and overall, 37 of 47 patients (79%) survived after ICV therapy.
      Nursing-home residence, acidosis, and hypoalbuminemia were significantly
      associated with the non-resolution of colitis in bivariate analyses (all p<0.01),
      whereas nursing-home residence and hypoalbuminemia showed non-significant trends
      toward association with death (p=0.07 and p=0.06, respectively). Multivariate
      logistic-regression models showed significant associations of acidosis with an
      incomplete response to ICV (p=0.02), of older age with death (p=0.04), and of
      hypoalbuminemia with both an incomplete response to ICV and death (both p=0.04).
      No complications were attributable to ICV. CONCLUSION: Complete resolution
      without surgery was achieved in 70% in this series of patients with severe C.
      difficile colitis who received adjunct ICV therapy. A clinical trial will be
      needed to determine whether ICV as compared with standard therapy alone can
      reduce the need for surgery with non-inferior or superior outcomes.

PMID- 23560734
TI  - Foetal and childhood growth and asthma in adult life.
AB  - AIM: Recent research suggests that asthma may originate through defects in the
      airway epithelium, acquired in utero, and an altered response to infections after
      birth. Here, we examine whether asthma in adult life is associated with reduced
      body size at birth and poor living conditions in childhood. METHODS: We studied
      658 people taking medication for asthma in a cohort of 13 345 men and women born
      in Helsinki, Finland, during 1934-1944. Their body and placental size at birth,
      and their living conditions and growth in childhood, had been recorded. RESULTS:
      The odds ratios for asthma were 0.93 (95% CI 0.89-0.97, p = 0.001) per cm
      increase in birth length and 0.92 (0.89-0.96, p < 0.001) per cm increase in the
      length of placental surface. After allowing for size at birth, growth during
      childhood was unrelated to asthma. People who were born into families of low
      socio-economic status were at increased risk of later asthma. CONCLUSION: Slow
      linear growth in utero, which could be a result of impaired placentation,
      increases the risk of later asthma. Slow linear growth may be associated with
      impaired development of the airways. Babies with impaired lung development born
      into families of low socio-economic status may be most vulnerable to the disease.

PMID- 23560735
TI  - Non-surgical prevention and management of scoliosis for children with Duchenne
      muscular dystrophy: what is the evidence?
AB  - A review was performed to examine the evidence for non-surgical interventions for
      preventing scoliosis and the need for scoliosis surgery in children with Duchenne
      muscular dystrophy. Medline and Embase databases and reference lists from key
      articles were searched. After the inclusion and exclusion criteria were applied,
      13 studies were critically appraised independently by two reviewers. The included
      studies examined spinal orthoses and steroid therapy. There were no studies with
      high levels of evidence (randomised or other controlled trials). The studies with
      the highest level of evidence were non-randomised experimental trials. There is
      some evidence that children with Duchenne muscular dystrophy who receive steroid
      therapy might have delayed onset of scoliosis, but more evidence is required
      about the long-term risks versus benefits of this intervention. There is weak
      evidence that spinal orthoses do not prevent and only minimally delay the onset
      of scoliosis. 

PMID- 23560736
TI  - Characterization of MYC-induced tumorigenesis by in situ lipid profiling.
AB  - We apply desorption electrospray ionization mass spectrometry imaging (DESI-MSI)
      to provide an in situ lipidomic profile of genetically modified tissues from a
      conditional transgenic mouse model of MYC-induced hepatocellular carcinoma (HCC).
      This unique, label-free approach of combining DESI-MSI with the ability to turn
      specific genes on and off has led to the discovery of highly specific lipid
      molecules associated with MYC-induced tumor onset. We are able to distinguish
      normal from MYC-induced malignant cells. Our approach provides a strategy to
      define a precise molecular picture at a resolution of about 200 MUm that may be
      useful in identifying lipid molecules that define how the MYC oncogene initiates
      and maintains tumorigenesis. 

PMID- 23560737
TI  - The nuclear mRNA export receptor Mex67-Mtr2 of Trypanosoma brucei contains a
      unique and essential zinc finger motif.
AB  - Trypanosoma brucei is the causative agent of Human African Trypanosomiasis.
      Trypanosomes are early diverged protozoan parasites and show significant
      differences in their gene expression compared with higher eukaryotes. Due to a
      lack of individual gene promoters, large polycistronic transcripts are produced
      and individual mRNAs mature by trans-splicing and polyadenylation. In the absence
      of transcriptional control, regulation of gene expression occurs post
      transcriptionally mainly by control of transcript stability and translation.
      Regulation of mRNA export from the nucleus to the cytoplasm might be an
      additional post-transcriptional event involved in gene regulation. However, our
      knowledge about mRNA export in trypanosomes is very limited. Although export
      factors of higher eukaryotes are reported to be conserved, only a few orthologues
      can be readily identified in the genome of T. brucei. Hence, biochemical
      approaches are needed to identify the export machinery of trypanosomes. Here, we
      report the functional characterization of the essential mRNA export factor
      TbMex67. TbMex67 contains a unique and essential N-terminal zinc finger motif.
      Furthermore, we could identify two interacting export factors namely TbMtr2 and
      the karyopherin TbIMP1. Our data show that the general heterodimeric export
      receptor Mex67-Mtr2 is conserved throughout the eukaryotic kingdom albeit
      exhibiting parasite-specific features.

PMID- 23560738
TI  - Practical coagulation for the blood banker.

PMID- 23560739
TI  - Image processing and recognition for biological images.
AB  - This paper reviews image processing and pattern recognition techniques, which
      will be useful to analyze bioimages. Although this paper does not provide their
      technical details, it will be possible to grasp their main tasks and typical
      tools to handle the tasks. Image processing is a large research area to improve
      the visibility of an input image and acquire some valuable information from it.
      As the main tasks of image processing, this paper introduces gray-level
      transformation, binarization, image filtering, image segmentation, visual object
      tracking, optical flow and image registration. Image pattern recognition is the
      technique to classify an input image into one of the predefined classes and also
      has a large research area. This paper overviews its two main modules, that is,
      feature extraction module and classification module. Throughout the paper, it
      will be emphasized that bioimage is a very difficult target for even state-of-the
      art image processing and pattern recognition techniques due to noises,
      deformations, etc. This paper is expected to be one tutorial guide to bridge
      biology and image processing researchers for their further collaboration to
      tackle such a difficult target.

PMID- 23560740
TI  - Etravirine for the treatment of HIV/AIDS.
AB  - INTRODUCTION: Etravirine (TMC125) is an orally administered second-generation non
      nucleoside reverse transcriptase inhibitor (NNRTI) that is approved in treatment
      experienced patients as addition to an optimized background therapy (OBT). AREAS
      COVERED: A Medline search was conducted of Phase II - IV clinical trials, as well
      as a review of abstracts from major HIV and infectious disease conferences from
      2010 - 2013, involving etravirine. EXPERT OPINION: Etravirine is a well-tolerated
      NNRTI with a good safety profile and a higher genetic barrier for resistance
      compared to first-generation NNRTIs. Rash is a potential side effect but remains
      mostly mild to moderate. The necessity of taking it twice daily with food (200 mg
      bid.), potential pharmacokinetic interactions and low concentrations in the
      central nervous system (CNS) represent limitations. The efficacy of once daily
      etravirine (400 mg qid.) and the use in treatment modification/simplification
      strategies requires further research. Despite its favorable profile, etravirine
      is currently not sufficiently investigated nor approved for use in treatment
      naive patients which should be balanced against its potential as a backup NNRTI
      and the broad cross-resistance conferred by etravirine failure to other NNRTIs.
      Etravirine should be avoided following treatment failure with regimens containing
      rilpivirine, another second-generation NNRTI.

PMID- 23560741
TI  - Self-etching dental adhesive containing a natural essential oil: anti-biofouling
      performance and mechanical properties.
AB  - This study assessed the anti-biofouling performance of an experimental adhesive
      system containing a naturally occurring essential vegetable oil and examined the
      following physical and mechanical properties: water sorption (WS) and solubility
      (SL), microtensile bond strength to dentin (MUTBS), and degree of conversion. The
      following six groups were tested: a self-etching experimental adhesive containing
      refined essential oil from the seeds of the Butia capitata tree (EAO); an oil
      free version of the experimental adhesive (EANO); one group without adhesive as
      the control (C); and the three following commercial self-etching adhesives:
      Clearfil Protect Bond (CPB), Clearfil SE Bond, and Adper SE Plus. The
      antibacterial effect was estimated by microbiological culture on selective/non
      selective media, and the results expressed as colony-forming units per unit
      weight of dry biofilm (CFU mg(-1)). The data were submitted to ANOVA and Tukey's
      post hoc test (alpha = 0.05). After 24 h, pH changes were similar in the storage
      medium of all tested adhesive systems. EAO showed similar levels of antimicrobial
      activity in a model biofilm microcosm as the commercial self-etching adhesive
      CPB. Both were effective against total microorganisms, aciduric bacteria,
      lactobacilli, and Streptococcus mutans. WS and SL were not affected by the
      presence of the essential oil; the values of EAO were similar to or less than
      those of commercial equivalents. The incorporation of an essential oil into an
      experimental adhesive did not influence its monomer conversion result. Immediate
      MUTBS values of EAO and EANO were similar and were greater than those of
      commercial equivalents. After storage for 6 months, the MUTBS of the EAO
      decreased significantly and became similar to the values of commercial
      equivalents, while the strength of the EANO was not affected.

PMID- 23560742
TI  - Moyamoya disease with mesial temporal sclerosis.
AB  - The combination of moyamoya syndrome and symptomatic mesial temporal sclerosis
      (MTS) has not previously been reported. The authors present the case of a 5-year
      old boy with symptomatic MTS who developed progressive moyamoya syndrome. This
      combination of progressive moyamoya and a structural seizure focus presented a
      unique clinical problem, with the natural history of MTS predicting a high
      likelihood of needing resection in the future, which could be challenging
      following any type of moyamoya-related revascularization surgery. In anticipation
      of this problem, the patient underwent resection of the right inferior and mesial
      temporal lobe followed by right pial synangiosis as a 1-day combined operation.
      Postoperatively he recovered well without any neurological deficits and had an
      uneventful hospital stay. This case of moyamoya is unique in its association with
      MTS, and for the simultaneous operations for pial synangiosis and temporal
      lobectomy, highlighting the importance of surgical planning in patients with dual
      pathological processes.

PMID- 23560743
TI  - Association between maternal education and diet of children at 9 months is
      partially explained by mothers' diet.
AB  - Infants of mothers of low educational background display consistently poorer
      outcomes, including suboptimal weaning diets. Less is known about the different
      causal pathways that relate maternal education to infants' diet. The present
      study aimed to test the hypothesis that the relationship between maternal
      education and infants' diet is mediated by mothers' diet. The analyses included
      421 mother-infant pairs from the Melbourne Infant Feeding Activity and Nutrition
      Trial (InFANT) Program. Dietary intakes were collected from mothers when infants
      were aged 3 months, using a validated food frequency questionnaire relating to
      the past year, and in infants aged 9 months using 3 * 24-h recalls. Principal
      component analysis was used to derive dietary pattern scores, based on
      frequencies of 55 food groups in mothers, and intakes of 23 food groups in
      infants. Associations were assessed with multivariable linear regression. We
      tested the product 'ab' to address the mediation hypothesis, where 'a' refers to
      the relationship between the predictor variable (education) and the mediator
      variable (mothers' diet), and 'b' refers to the association between the mediator
      variable and the outcome variable (infants' diet), controlling for the predictor
      variable. Maternal scores on the 'Fruit and vegetables' dietary pattern partially
      mediated the relationships between maternal education and two infant dietary
      patterns, namely 'Balanced weaning diet' [ab = 0.11; 95% confidence interval
      (CI): 0.04; 0.18] and 'Formula' (ab = -0.08; 95%CI: -0.15; -0.02). These findings
      suggest that targeting pregnant mothers of low education level with the aim of
      improving their own diet may also promote better weaning diets in their infants. 

PMID- 23560744
TI  - Barriers to and facilitators for screening women for intimate partner violence in
      surgical fracture clinics: a qualitative descriptive approach.
AB  - BACKGROUND: Intimate Partner Violence (IPV) is a major health issue that involves
      any physical, sexual or psychological harm inflicted by a current or former
      partner. Musculoskeletal injuries represent the second most prevalent clinical
      manifestation of IPV. Health care professionals, however, rarely screen women for
      IPV. Using qualitative methods, this study aimed to explore the perceived
      barriers to IPV screening and potential facilitators for overcoming these
      barriers among orthopaedic surgeons and surgical trainees. METHODS: We conducted
      three focus groups with orthopaedic surgeons, senior surgical trainees, and
      junior surgical trainees. A semi-structured focus group guide was used to
      structure the discussions. Transcripts and field notes from the focus groups were
      analyzed using the qualitative software program N'Vivo (version 10.0; QSR
      International, Melbourne, Australia). To further inform our focus group findings
      and discuss policy changes, we conducted interviews with two opinion leaders in
      the field of orthopaedics. Similar to the focus groups, the interviews were
      digitally recorded and transcribed, and then analyzed. RESULTS: In the analysis,
      four categories of barriers were identified: surgeon perception barriers;
      perceived patient barriers; fracture clinic barriers and orthopaedic health care
      professional barriers. Some of the facilitators identified included availability
      of a crisis team; development of a screening form; presence of IPV posters or
      buttons in the fracture clinic; and the need for established policy or government
      support for IPV screening. The interviewees identified the need for: the
      introduction of evidence-based policy aiming to increase awareness about IPV
      among health care professionals working within the fracture clinic setting,
      fostering local and national champions for IPV screening, and the need to
      generate change on a local level. CONCLUSIONS: There are a number of perceived
      barriers to screening women in the fracture clinic for IPV, many of which can be
      addressed through increased education and training, and additional resources in
      the fracture clinic. Orthopaedic health care professionals are supportive of
      implementing an IPV screening program in the orthopaedic fracture clinic.

PMID- 23560745
TI  - Evaluation of DNA extraction methods for Bacillus anthracis spores isolated from
      spiked food samples.
AB  - AIMS: Nine commercial DNA extraction kits were evaluated for the isolation of DNA
      from 10-fold serial dilutions of Bacillus anthracis spores using quantitative
      real-time PCR (qPCR). The three kits determined by qPCR to yield the most
      sensitive and consistent detection (Epicenter MasterPure Gram Positive; MoBio
      PowerFood; ABI PrepSeq) were subsequently tested for their ability to isolate DNA
      from trace amounts of B. anthracis spores (approx. 6.5 * 10(1) and 1.3 * 10(2) 
      CFU in 25 ml or 50 g of food sample) spiked into complex food samples including
      apple juice, ham, whole milk and bagged salad and recovered with immunomagnetic
      separation (IMS). METHODS AND RESULTS: The MasterPure kit effectively and
      consistently isolated DNA from low amounts of B. anthracis spores captured from
      food samples. Detection was achieved from apple juice, ham, whole milk and bagged
      salad from as few as 65 +/- 14, 68 +/- 8, 66 +/- 4 and 52 +/- 16 CFU,
      respectively, and IMS samples were demonstrated to be free of PCR inhibitors.
      CONCLUSIONS: Detection of B. anthracis spores isolated from food by IMS differs
      substantially between commercial DNA extraction kits; however, sensitive results
      can be obtained with the MasterPure Gram Positive kit. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The extraction protocol identified herein combined with IMS is novel
      for B. anthracis and allows detection of low levels of B. anthracis spores from
      contaminated food samples.

PMID- 23560746
TI  - Theoretical elucidation of the origin for assembly of the DAP12 dimer with only
      one NKG2C in the lipid membrane.
AB  - In this work, we have investigated in details the origin of the assembly of the
      DAP12 dimer with only one NKG2C in the activating immunoreceptor complex from
      thew two aspects of electronic properties and dynamic structures by performing
      density functional theory (DFT) calculations and molecular dynamics (MD)
      simulations. In the DFT calculations, we studied the aggregation ability of the
      NKG2C(TM) with the DAP12(TM) dimer and the DAP12(TM)-DAP12(TM)-NKG2C(TM) complex
      by analyzing the electrostatic potentials and frontier molecular orbitals (FMOs),
      and in the MD simulations we mainly investigated the dynamic structures of the
      DAP12(TM)-DAP12(TM)-NKG2C(TM) complex and its mutants, as well as the tetramer
      complex consisting of two DAP12(TM) and two NKG2C(TM) helixes without any
      restriction. Through the studies of the electrostatic potential, the FMOs, and
      the dynamic structures, we have provided reasonable explanations to some extent
      for the experimental observation that only one NKG2C can associate with the DAP12
      homodimer. The present theoretical results are expected to give valuable
      information for further studying the assembly between receptors and signaling
      subunits.

PMID- 23560747
TI  - Altering colloidal surface functionalization using DNA encapsulated inside
      monodisperse gelatin microsphere templates.
AB  - Soluble oligonucleotides are typically introduced to bulk solution to promote
      hybridization activity on DNA-functionalized surfaces. Here, an alternative
      approach is explored by encapsulating secondary target strands inside
      semipermeable colloidal satellite assemblies, then triggering their release at 37
      degrees C for subsequent surface hybridization activity. To prepare DNA-loaded
      satellite assemblies, uniform gelatin microspheres are fabricated using
      microfluidics, loaded with 15 base-long secondary DNA targets, capped with a
      polyelectrolyte bilayer, and finally coated with a monolayer of polystyrene
      microspheres functionalized with duplexes comprised of immobilized probes and
      soluble, 13 base-long hybridization partner strands. Once warmed to 37  degrees
      C, secondary DNA targets are released from the gelatin template and then
      competitively displace the shorter, original hybridization partners on the
      polystyrene microspheres.

PMID- 23560748
TI  - Implant retainers for free-end removable partial dentures affect mastication and
      nutrient intake.
AB  - OBJECTIVES: This study measured swallowing threshold parameters and nutrient
      intake in partially dentate subjects rehabilitated by conventional free-end
      removable partial dentures (RPD) and by RPD over posterior implant retainers and
      ball attachments (BA). MATERIALS AND METHODS: Eight subjects (two men and six
      women; mean age 60.1 +/- 6.6 years old) received conventional total maxillary
      dentures and free-end RPD in the mandible. Two months after denture insertion,
      swallowing threshold and nutrient intake assessments occurred, which included an
      evaluation of the number of masticatory cycles and medium particle size (X50) of
      a silicone test material (Optocal). A 3-day food diary verified nutrient intake
      based on a standard Brazilian Food Composition Table. Then, osseointegrated
      implants were placed bilaterally in the mandibular first molar region, followed
      by BA, which was fitted in the RPD bases after healing. After 2 months of the RPD
      over implants and BA use, variables were again assessed. Wilcoxon signed rank
      tests evaluated the data (P < 0.05). RESULTS: Masticatory cycles did not differ
      (P > 0.05); however, subjects showed decreased X50 values at the swallowing
      moment (P = 0.008) and increased daily energy (P = 0.008), carbohydrate (P =
      0.016), protein (P = 0.023), calcium (P = 0.008), fiber (P = 0.016), and iron (P
      = 0.016) intake with RPD implants and BA inserts. No differences were found in
      fat consumption (P > 0.05). CONCLUSION: Implants and BA retainers over a free-end
      RPD resulted in smaller swallowed median particle size and improved nutrient
      intake.

PMID- 23560751
TI  - [Medical elements in the Parish Church of Saint George in Lovran (Croatia)].
AB  - For some reason, the sacral heritage of Lovran and its surroundings has escaped
      the eye of medical historians, until now. seeing that the Parish Church of st
      George in Lovran holds a central position in this heritage, the authors provide
      an analysis of medical elements in the church. The analysis has focused on three
      aspects. The first aspect are medical elements, especially the anthropological
      features of characters depicted on the frescoes, which belong to the earliest and
      most representative of the whole region. The second are Glagolithic inscriptions
      relevant for the history of medicine and health culture. The third is the
      iconography of patron saints against a variety of diseases (featured on
      paintings, altars or sculptures), paying particular attention to relevant medical
      imagery of st George as the church's patron saint. relying on a well developed
      method for analysing medical elements in the sacral heritage of Croatia and
      abroad, the authors seek to fill the gaps in this medical historical mosaic by
      investigating the parish church of Lovran.

PMID- 23560750
TI  - Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich
      repeat kinase 2) monoclonal antibodies.
AB  - Missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a major cause of
      PD (Parkinson's disease). Several antibodies against LRRK2 have been developed,
      but results using these polyclonal antibodies have varied widely leading to
      conflicting conclusions. To address this challenge, the Michael J. Fox Foundation
      for Parkinson's Research generated a number of monoclonal antibodies targeting
      epitopes across the LRRK2 protein. In the present paper, we report optimized
      protocols and results for ten monoclonal antibodies for immunoblotting,
      immunohistochemistry, immunoprecipitation and kinase activity assays, in rat,
      mouse and human brain tissue. Several efficacious antibodies were identified, but
      results demonstrate that the mouse monoclonal N241A/34 is suitable for most
      applications, with the best overall rabbit monoclonal antibody being c41-2. These
      antibodies produced a dominant band of the expected size via immunoblotting and a
      lack of labelling in tissue derived from LRRK2-knockout animals under optimized
      conditions. A significant proportion of LRRK2 protein localizes to insoluble
      fractions and no evidence of truncated LRRK2 protein was detected in any fraction
      from rodent or human tissues. An assay was developed for the robust detection of
      LRRK2 kinase activity directly from frozen mouse and human brain tissue, but
      precipitous declines in activity were observed that corresponded to increasing
      post-mortem intervals and processing times. Finally, we demonstrate the highest
      levels of brain-localized LRRK2 in the striatum, but note differential expression
      patterns between rat and mouse in both striatum and cortex. Anti-LRRK2 monoclonal
      antibodies that are unlimited in availability together with the proposed
      standardized protocols should aid in the definition of LRRK2 function in both
      health and disease.

PMID- 23560752
TI  - Stolen and lost copies of Vesalius's Fabrica.
AB  - Thefts and losses of precious books are not rare. Here we report several
      incidents concerning vesalius's Fabrica: the fire of the University Library of
      Leuven in Belgium, the fate of the collection of the Leopoldina Library of Halle
      in Germany, the thefts from the Crerar Library in Chicago and in Christ Church
      College in Oxford, the disappearance of an exceptionally beautiful 'royal' copy
      from the Castle of Argenteuil (Belgium), and other Fabrica's missing at the
      Franeker Library in the Netherlands and at the Library of oradea in West Romania.
      Finally the means of protecting precious book collections are discussed in short
      as well as the importance of book identification.

PMID- 23560753
TI  - Beer and wine in antiquity: beneficial remedy or punishment imposed by the Gods?
AB  - Different types of alcoholic beverages such as wine and beer were used in ancient
      times for various medicinal purposes. Being the oldest and probably the most
      widely used drugs, they were known to have some therapeutic value, in addition to
      the vital part they played in the daily life of people. Ethanol is produced by
      fermentation of a variety of plants and consumed either in a diluted form or
      concentrated by distillation to concoct alcoholic beverages. Beer made of
      fermented barley is an alcoholic drink that was believed to contain a spirit or a
      god. It is a drink of relatively low alcohol content with supernatural
      properties. The same was believed for wine. Considered to be divine, these
      beverages were the long sought elixirs of life and appeared in religious
      ceremonies, in mythology, and in social meals, such as the Greek symposia. In
      addition, these alcoholic drinks were considered to be a remedy for practically
      every disease and, therefore, were a common ingredient in ancient prescriptions.
      They were used as anaesthetics that dull the pain, as stimulants, as analgesics,
      as antiseptics to cleanse wounds and relieve pain, as emetics, as digestives, as
      antidotes for plant poisoning, for bites and stings, and as purifiers. However,
      we should not overlook the harmful effects of alcohol abuse such as drunkenness,
      chronic liver disease and, in modern terminology, infirmities that included
      pancreatitis, cardiomyopathy, peripheral neuropathy, dementia, and central
      nervous system disorders.

PMID- 23560754
TI  - [Hygienic and sanitary issues related to funerals in Pula at the end of the
      eighteenth and in the first half of the nineteenth century].
AB  - In Pula, like in the rest of Europe since the beginning of the Early Middle Ages,
      cemeteries were situated in major churches for almost an entire millennium, with
      many sanitary hygienic consequences for the town, until the new cemetery moved
      outside the town walls. At the end of the eighteenth century, the question of
      urban hygiene, especially issues related to urban burial, came into the spotlight
      of scientific thinking. Churches were recognised as a true threat when it came to
      the spread of diseases, and the only solution to this intolerable situation was
      to move cemeteries away from the city and separate the world of the living from
      the world of the dead. With medieval burial practices ad sanctos abandoned, the
      enlightened thought set the ground for new solutions for healthcare, urban, and
      social issues. The relocation of the cemetery outside the city walls in 1846,
      relieved Pula of the great hygienic burden, rightly considered a threat for
      public health.

PMID- 23560755
TI  - [The influence of infectious diseases on ancient maritime navigation and the
      earliest attempts to control them through codes].
AB  - This article describes the influence of infectious diseases on ancient maritime
      navigation and the early attempts to prevent their spread with legal regulations.
      In ancient times, the greatest health hazard for sailors were poor hygienic
      conditions, water supply, nutrition, accommodation, air, and lighting on board.
      These conditions favoured the development and transmission of infectious
      diseases. The oldest legal attempts to regulate maritime navigation and
      indirectly improve health conditions on board are found in the Code of Bilalama
      from the beginning of the 20th century BC and in the Babylonian Code of Hammurabi
      from the 18th century BC. The first regulations dealing with infectious diseases
      are found in the Book of Leviticus, 59 altogether, which are later also found in
      the Bible. The rhodian maritime law from the 7th to 9th century AD also contains
      health regulations on accommodation on board and defines minimum water
      requirements. Greek and Roman vessels were the first to take physicians on board.

PMID- 23560756
TI  - Alexandre Yersin's explorations (1892-1894) in French Indochina before the
      discovery of the plague bacillus.
AB  - Alexandre Yersin, the great French discoverer of yersinia pestis, was a keen
      explorer of unknown lands. At the age of 30, a member of the French Colonial
      Health service, he set off to fulfil his intimate dream and explore other
      continents. For almost two years and three long expeditions, he journeyed through
      widely unknown regions in the province of the French Indochina, in southeast
      Asia, territories of Vietnam, Cambodia and Laos. This article presents vignettes
      from his explorations. During his difficult travels, he carefully planned and
      noted his itineraries; designed new routes, but also observed and recorded
      sociodemographic and environmental data and unidentified diseases. The immature
      science of late 19th century geography had the strength to allure such an
      influential medical figure and place him among the early medical geographers. His
      journeys, observations and recordings brought to Yersin great experience, and he
      made his most important scientific contributions after he had concluded his
      explorations.

PMID- 23560757
TI  - Jerome Lejeune (1926-1994): father of modern genetics.
AB  - Jerome Lejeune's greatest achievement was the discovery of the genetic basis of
      Down's syndrome, which he named trisomy 21. His important research in human
      genetics, as well as his humanitarian spirit and fight against therapeutic
      abortion, rightly led to his recognition as the founder of modern genetics.

PMID- 23560758
TI  - Beginning of biometeorology in Abbazia/Opatija.
AB  - In addition to health facilities and many other organizations, there was also a
      functioning weather station in the health and seaside resort of Abbazia/Opatija,
      known as the Nice of the Austrian riviera. Formal observation of weather in
      Abbazia/Opatija began in 1886 with the setting up of the weather station in
      Angiolina Park. During the period 1898-1915, the warden of this station and data
      collector was the local doctor, dr Franz Tripold. On the basis of the collected
      data, he wrote the first study of Abbazia/Opatija's climate and its effects on
      people. The study das Klima in Abbazia was published in 1906 in Abbazia als
      Kurort on the 60th birthday of Professor Julius Glax, head of the health resort
      in Abbazia/Opatija. The study highlighted the physiological effects of the
      maritime climate on people and examined the beneficial effects of the local
      climate on patients. The weather station in Opatija is still operating in
      Angiolina Park. Weather parameters to be gathered were determined by the First
      international Meteorological Congress in Vienna in 1873 and are still valid. The
      parameter of human well being/bio meteorological prognosis has been added. Today,
      the collected data are sent to the National Meteorological and Hydrological
      service in Zagreb, from where they are returned to Opatija to be displayed on a
      screen in the town centre to help people to plan their daily activities and take
      appropriate measures to protect their health, which is especially important for
      patients.

PMID- 23560759
TI  - [On the occasion of the 575th anniversary of the first mention of an apothecarius
      in Rijeka- Dilemmas about and a brief review of the history of pharmacy in Rijeka
      from its beginnings to the foundation of Jadran-Galenski Laboratorij joint-stock
      company in 1991].
AB  - This article seeks to elucidate the beginnings of pharmaceutical practice in
      Rijeka. The first problem is to date the opening of the first pharmacy. According
      to the majority of relevant sources, history of pharmacy in Rijeka has been
      documented since the beginning of the 18th century, while the mentions of
      pharmacies in the middle of the 15th century are uncertain and less probable. The
      article also brings an overview of how pharmaceutical practice developed until
      the end of the 20th century and singles out the foundation of Jadran Galenski
      Laboratorij as the largest pharmaceutical company in the area.

PMID- 23560760
TI  - Can we still hear the Cro-magnon man?
AB  - This paper is an essay to connect with the stone Age coastal hunters who
      sheltered 28,000 years ago in the caves of today's italian Mediterranean sea
      shore cliffs. We have focused on the archaeological Gravettian layer in the
      Cavillon cave from Grimaldi occupied by Cro Magnons (informal name for
      Anatomically Modern Humans of the European Upper Paleolithic), which demonstrates
      the technical skills of the phase. Cro Magnons, like Neanderthals, were
      seasonally nomadic; however, the diversity of the resources exploited within the
      territory along the Grimaldi sea coast suggests a longer term site within which a
      complex symbolic culture developed.

PMID- 23560761
TI  - [Patron saints and Christian perception of health and illness].
AB  - As a religion based on the teaching of Jesus Christ, from the outset Christianity
      has developed a completely different attitude toward health and illness than the
      Old Testament. Health and illness are now viewed through the eyes of Jesus Christ
      the redeemer, who accepted each and every man. The history of Christianity has
      had its episodes of masochistic attitude toward illness, but today it clearly
      underscores the need to fight it with any means available, but it also teaches to
      accept what can not be changed. Saints are often patrons against diseases they
      had to endure. However, this is not their main role. To this day many seem to
      miss the main point their heritage, but see them as miracle healers. This
      misperception of miracle needs revising as well as the simplistic interpretation
      of the healing powers of relics (viewed as a demiurge of sort) and of the private
      vows and votive offerings.

PMID- 23560763
TI  - Photophysical properties of self-assembled multinuclear platinum metallacycles
      with different conformational geometries.
AB  - In this work, spectroscopic techniques and quantum chemistry calculations were
      used to investigate the photophysical properties of various multinuclear platinum
      complexes with different conformational geometries. This suite of complexes
      includes a Pt-pyridyl square, a Pt-carboxylate triangle, and a mixed Pt-pyridyl
      carboxylate rectangle, as well as two mononuclear Pt model complexes. Studying
      the individual molecular precursors in the context of larger assemblies is
      important to provide a complete understanding of the factors governing the
      observed photophysical properties of a given system. The absorption and emission
      bands of the parent linear dipyridyl donor (ligand 1) are largely preserved in
      the [4 + 4] square and the multicomponent [4 + 2 + 2] rectangle (3 and 4,
      respectively), with significant red shifts. The [3 + 3] Pt-carboxylate triangle
      containing p-phthalic acid is nonemissive. Phosphorescence and nanosecond
      transient spectroscopy on 3 and 4 reveal that the introduction of platinum atoms
      enhances spin-orbital coupling, thereby increasing the rate of intersystem
      crossing. This phenomenon is consistent with the low fluorescence quantum yields
      and short fluorescence lifetimes of 3 and 4. Moreover, the electronic structures
      for the ground state and low-lying excited states of these compounds were studied
      using quantum chemistry calculations. The fluorescent states of the platinum
      complexes are local excited states of ligand-centered pi-pi* transition features,
      whereas the nonfluorescent states are intramolecular charge-transfer states.
      These low-lying intramolecular charge-transfer states are responsible for the
      nonemissive nature of small molecules 1 and 2 and triangle 5. As the interactions
      between these components determine the properties of their corresponding
      assemblies, we establish novel excited-state decay mechanisms which dictate the
      observed spectra.

PMID- 23560762
TI  - Protection of renal impairment by angiotensin II type 1 receptor blocker in rats
      with post-infarction heart failure.
AB  - Renal impairment is a frequent accompaniment post-myocardial infarction (MI)
      heart failure. However, the mechanisms and predictors are yet poorly understood.
      The present study aimed to explore early markers for renal impairment and to test
      the hypothesis that angiotensin II type 1 receptor (AT1R) blocker exerted
      renoprotection by regulating local angiotensin II receptors post-MI heart
      failure. Sprague-Dawley rats underwent ligation of the left descending coronary
      artery and were treated with losartan (20 mg/kg/day) or vehicle for 3 or 9 weeks.
      Samples of urine, blood, and kidney were collected for assessment of renal
      function, histology, and protein changes. The current study revealed that blood
      cystatin C, rather than serum creatinine and blood urea nitrogen, as well as
      urine proteins, increased post-MI heart failure significantly. These changes were
      associated with increased immunohistochemical staining of AT1R and AT2R proteins,
      accompanied by increased renal fibrosis, tubular necrosis, and inflammatory cell
      infiltration. Treatment with losartan for MI rats significantly attenuated
      upregulated AT1R but not AT2R. Losartan also decreased blood cystatin C levels
      and attenuated renal fibrosis, tubular necrosis, and inflammatory cell
      infiltration. In conclusion, blood cystatin C may be a better marker for early
      renal impairment. AT1R blockers modulated local angiotensin II receptors, as well
      as inflammatory reaction and profibrotic effects, providing potential clinical
      application in the setting of cardiorenal syndrome post-MI.

PMID- 23560764
TI  - Ursodeoxycholic acid increases differentiation and mineralization and neutralizes
      the damaging effects of bilirubin on osteoblastic cells.
AB  - BACKGROUND: Osteoporosis resulting from decreased bone formation is a common
      complication in patients with chronic cholestasis. Lithocholic acid (LCA) and
      bilirubin may play a role in osteoporosis given that both substances have
      detrimental effects on survival of human osteoblasts, the cells involved in bone
      formation. AIMS: As ursodeoxycholic acid (UDCA) improves cholestasis, we have
      assessed if this bile acid may neutralize the harmful effects of LCA, bilirubin
      and sera from jaundiced patients on osteoblastic cells. METHODS: The experiments
      were performed in primary human osteoblasts and human osteosarcoma cell line
      (Saos-2) at different times and concentrations of UDCA, LCA, cholic acid (CA),
      bilirubin and sera from jaundiced patients to assess cell viability,
      differentiation and mineralization. RESULTS: UDCA significantly decreased cell
      survival at concentrations 10 times higher (1 mM) than that observed with LCA,
      whereas CA did not decrease osteoblast survival. UDCA (100 MUM) neutralized the
      damaging effects of bilirubin (50 MUM) and sera from jaundiced patients on
      survival. Moreover, UDCA (1 MUM and 10 MUM) increased osteoblast differentiation
      in cells treated with harmful concentrations of LCA or bilirubin. UDCA (100 MUM)
      increased cell differentiation in osteoblasts cultured with a mix of serum from
      cholestatic patients by 23%. Furthermore, UDCA increased osteoblast
      mineralization by 35% and neutralized the negative consequences of 50 MUM
      bilirubin. CONCLUSIONS: UDCA increases osteoblast differentiation and
      mineralization, and neutralizes the detrimental effects of lithocholic acid,
      bilirubin and sera from jaundiced patients on osteoblastic cells. Therefore, UDCA
      may exert a favourable effect on bone in patients which chronic cholestasis.

PMID- 23560765
TI  - Socioeconomic status and risk of dental caries in Japanese preschool children:
      the Osaka Maternal and child health study.
AB  - OBJECTIVES: Investigations concerning the relationship between socioeconomic
      status and dental caries have been conducted mainly in Western countries. The
      purpose of this longitudinal study was to examine the impact of socioeconomic
      factors, such as maternal occupation, household income, and parental educational
      levels, on the risk of dental caries in young Japanese children. METHODS: A
      cohort of 315 preschool children was used. Information pertaining to exposure and
      potentially confounding factors was obtained by means of questionnaires
      administered to expectant mothers prior to delivery and subsequently when their
      children were in the ranges of 2-9, 16-24, 29-39, and 41-49 months of age.
      Outcome data were collected when the children were between 41 and 50 months old.
      Children were classified as having dental caries if one or more primary teeth had
      decayed or had been filled. RESULTS: Compared with maternal or paternal education
      of less than 13 years, maternal or paternal education of 15 years or longer was
      significantly associated with a decreased risk of dental caries in children: the
      adjusted odds ratios for maternal and paternal education levels >= 15 years
      compared with <13 years of maternal and paternal education were 0.32 (95 percent
      confidence interval: 0.14-0.71) and 0.45 (95 percent confidence interval: 0.23
      0.88), respectively. No relationship between maternal occupation or household
      income and the risk of children's dental caries was found. CONCLUSIONS: Higher
      levels of parental education, in particular maternal education, may be associated
      with reduced risk of dental caries in preschool children.

PMID- 23560766
TI  - Dynamic evaluation of cell surface N-glycan expression via an electrogenerated
      chemiluminescence biosensor based on concanavalin A-integrating gold-nanoparticle
      modified Ru(bpy)3(2+)-doped silica nanoprobe.
AB  - A sandwich electrogenerated chemiluminescence (ECL) biosensor was fabricated
      based on concanavalin A (Con A)-integrating gold-nanoparticle-modified
      Ru(bpy)3(2+)-doped silica nanoprobe (Au-RuSiO2 NPs) for in situ and dynamically
      evaluating cell surface N-glycan expression. Owing to the specific recognition of
      Con A with mannose and the core trimannoside fragment of N-glycan and the
      effective ECL amplification of Au-RuSiO2 NPs, the as-proposed biosensor exhibited
      excellent analytical performance toward the cytosensing of K562 cells with a wide
      detection linear range from 1.0 * 10(3) to 1.0 * 10(7) cells mL(-1) and a
      detection limit of 600 cells mL(-1). More importantly, the strategy was
      successfully applied to evaluate cell surface N-glycan expression under different
      external stimuli of inhibitors and enzyme. This biosensor is endowed with
      feasibility and reliability of generating sensitive insight into the majority of
      N-glycan expression on the cell surface. Furthermore, the biosensor was employed
      to dynamically profile cell surface N-glycan expression at different phases of
      cell growth in vitro. This biosensor is promising in studying and elucidating the
      N-glycan function in biological and physiological processes.

PMID- 23560767
TI  - Historical factors influencing medical education research productivity.
AB  - The author explores the reasons why both Canada and the Netherlands have a
      productivity in medical education research that is disproportionate to their
      size. He suggests that the historical introduction of problem-based learning
      early in both countries by McMaster and Maastricht, respectively, with a
      commitment for programmatic and broader research in both institutions has left
      this legacy.

PMID- 23560768
TI  - Childhood craniopharyngioma: 20-year institutional experience in Western
      Australia.
AB  - AIM: A retrospective audit was undertaken to evaluate modes of presentation and
      treatment outcomes for craniopharyngioma in a single paediatric institution over
      a 20-year period. METHODS: A search of the neurosurgical and histopathological
      databases for patients under 21 years of age treated for craniopharyngioma
      between 1990 and 2010 was performed at our institution. The clinical records of
      eligible patients were reviewed and information regarding presentation, medical
      and surgical management and post-treatment outcome were extracted and collated.
      RESULTS: Of 10 evaluable patients, the commonest presenting symptoms were
      headache and visual impairment. Clinical and biochemical evaluation undertaken
      prior to surgery revealed visual dysfunction in 70% and pituitary deficit in 30%.
      Gross total resection was achieved in 40% but was curative in only 20%. The
      remaining 80% required further surgical and/or radiotherapeutic intervention.
      Seven patients had radiation therapy with stabilisation in 70%. Multiple
      pituitary hormone deficiency evolved in all patients over time, while visual
      impairment worsened in 30% post-operatively and improved in 20%. Obesity was
      present in 50% after a mean follow-up interval of 5.6 years and was apparent
      within 1 year of initial surgery in 30%. Although neurocognitive, psychological
      and behavioural problems were noted for some patients during medical review, only
      20% of patients were formally assessed. CONCLUSIONS: Craniopharyngioma is
      associated with significant long-term morbidity. Attention to an integrated care
      pathway that includes standardised neurocognitive and psychological and
      behavioural assessment would facilitate early appropriate intervention and
      support leading to an improved quality of life for children with
      craniopharyngioma.

PMID- 23560769
TI  - Postoperative parotid abscess: another occult source of severe sepsis.

PMID- 23560770
TI  - Iliopsoas abscess: role of computed tomography with multiplanar reformatted
      images for defining the etiology.

PMID- 23560771
TI  - Neutrophils release extracellular DNA traps during storage of red blood cell
      units.
AB  - BACKGROUND: Blood transfusion is associated with an increased risk of organ
      damage, infection, and alloimmunity. Neutrophil extracellular traps (NETs) are
      extracellular chromatin fibers decorated with neutrophil granular proteins that
      have been linked to cytotoxicity, thrombosis, and autoimmunity. We questioned
      whether neutrophils in blood products release NETs during storage and thus could
      contribute to adverse reactions from blood transfusions. STUDY DESIGN AND
      METHODS: We analyzed supernatants and blood smears of human red blood cell (RBC)
      units that either were or were not leukoreduced before storage for markers of
      NETs. RESULTS: We identified extracellular DNA, which was associated with
      histones and myeloperoxidase, a marker of neutrophil granules, in supernatants
      and blood smears of nonleukoreduced RBC units. These markers of NETs were absent
      in leukoreduced RBC units. Importantly, NETs passed through blood transfusion
      filters and could therefore potentially be infused into patients. CONCLUSIONS:
      Our studies indicate that NETs are liberated during storage of nonleukoreduced
      RBC units. Future studies should address whether NETs in RBC units could
      potentially contribute to transfusion-associated complications.

PMID- 23560772
TI  - Hybrid sensor kinase PA1611 in Pseudomonas aeruginosa regulates transitions
      between acute and chronic infection through direct interaction with RetS.
AB  - Pseudomonas aeruginosa causes serious acute and chronic infections in humans.
      Major differences exist in disease pathogenesis, clinical treatment and outcomes
      between acute and chronic infections. P. aeruginosa acute infection
      characteristically involves the type III secretion systems (T3SS) while chronic
      infection is often associated with the formation of biofilms, a major cause of
      difficulties to eradicate chronic infections. The choice between acute and
      chronic infection or the switch between them by P. aeruginosa is controlled by
      regulatory pathways that control major virulence factors and genes associated
      with biofilm formation. In this study, we characterized a hybrid sensor kinase
      PA1611 that controls the expression of genes associated with acute and chronic
      infections in P. aeruginosa PAO1. Expression of PA1611 completely repressed T3SS
      and swarming motility while it promoted biofilm formation. The protein PA1611
      regulates two small RNAs (sRNAs), rsmY and rsmZ which in turn control RsmA.
      Independent of phosphate relay, PA1611 interacts directly with RetS in vivo. The
      positive effect of RetS on factors associated with acute infection could
      presumably be restrained by PA1611 when chronic infection conditions are present.
      This RetS-PA1611 interaction, together with the known RetS-GacS interaction, may
      control disease progression and the lifestyle choice of P. aeruginosa.

PMID- 23560773
TI  - Unaccompanied refugee children--vulnerability and agency.
AB  - The numbers of refugee adolescents that arrive in Europe without their families
      has increased in recent years, particularly in Sweden. Research has demonstrated
      that these children have high rates of mental health problems, particularly
      depression and post-traumatic stress disorder, during the first years after
      resettlement. Despite this, there are also indications that many of these
      unaccompanied children are resourceful and arrive with a clear vision of a
      positive future in the new country. Follow-up studies in the United States and
      Norway have indicated fairly good social outcomes in the long term. CONCLUSION:
      The education and care that unaccompanied minors receive during the first years
      after resettlement, together with their own drive to create a positive future,
      are key factors in their mental health and long-term adjustment.

PMID- 23560774
TI  - An update on the pharmacotherapy of neovascular age-related macular degeneration.
AB  - INTRODUCTION: Neovascular age-related macular degeneration (AMD) is currently the
      most common cause of legal blindness in industrialized countries. The advent of
      pharmacotherapy with intravitreal VEGF inhibitors has greatly improved outcomes
      for the treatment of this disease. AREAS COVERED: The present review is divided
      into two major sections: the period prior to the use of anti-VEGF agents
      (triamcinolone acetonide, verteporfin photodynamic therapy) and the period
      following their introduction (pegaptanib sodium, bevacizumab, ranibizumab,
      aflibercept). The main pharmacological and clinical characteristics of each
      therapy are summarized. EXPERT OPINION: Monotherapy with anti-VEGF agents is
      currently the 'gold standard' for treating neovascular AMD, but, with several
      drug choices and various different dosing regimens available, there is still wide
      variability in how individual clinicians manage their patients. Despite improved
      visual outcomes, there remains a significant unmet need for better treatments as
      the frequent office visits and injections associated with anti-VEGF therapy are
      costly and place a significant burden on patients, their family members and
      physicians.

PMID- 23560775
TI  - Reduced re-infection rates with postoperative oral antibiotics after two-stage
      revision hip arthroplasty.
AB  - BACKGROUND: Surgeons are often trying to decreased reinfection rates following
      two-stage reimplantation arthroplasty, which range from 3.2% to 13% because
      multiple staged revision procedures for infection can be costly and have high
      morbidity. We therefore asked: (1) Did the use of postoperative oral antibiotics
      reduce reinfection rates after 2-staged revision of THA? And (2) how did this
      compare with the infection rate after aseptic revision procedures? METHODS: We
      identified all patients who underwent two-stage revision THA for a periprosthetic
      deep hip infection and found 66 patients (67 hips) who had a minimum 24 months'
      followup. Twenty-two of the 66 procedures (33%) were followed by a minimum of 14
      days of postoperative oral antibiotics (mean, 36 days; range, 14 days to
      lifelong), while 44 were prescribed only immediate parenteral postoperative
      antibiotic therapy (mean, 1.3 days; range, 1-3 days). We then identified 407
      patients (410 hips) who underwent aseptic revision hip arthroplasty and evaluated
      the infection rate in these patients for comparison; these patients were treated
      with 24 hours of postoperative parenteral antibiotics. The authors used
      previously described creteria to establish the presence of infection. RESULTS:
      There were no reinfections in the group receiving oral postoperative antibiotics
      compared to six reinfections (13.6%) in the 44 patients not receiving oral
      antibiotics. We observed infection in 2 of the 410 hips (0.5%) revised for
      aseptic reasons. CONCLUSIONS: We believe that our findings warrant further
      investigation for using postoperative oral antibiotics after reimplantation for
      periprosthetic infection in an effort to decrease the likelihood and risks
      associated with additional revision arthroplasty procedures.

PMID- 23560776
TI  - A general protocol for determining the structures of molecularly ordered but
      noncrystalline silicate frameworks.
AB  - A general protocol is demonstrated for determining the structures of molecularly
      ordered but noncrystalline solids, which combines constraints provided by X-ray
      diffraction (XRD), one- and two-dimensional solid-state nuclear magnetic
      resonance (NMR) spectroscopy, and first-principles quantum chemical calculations.
      The approach is used to determine the structure(s) of a surfactant-directed
      layered silicate with short-range order in two dimensions but without long-range
      periodicity in three-dimensions (3D). The absence of long-range 3D molecular
      order and corresponding indexable XRD reflections precludes determination of a
      space group for this layered silicate. Nevertheless, by combining structural
      constraints obtained from solid-state (29)Si NMR analyses, including the types
      and relative populations of distinct (29)Si sites, their respective (29)Si-O
      (29)Si connectivities and separation distances, with unit cell parameters (though
      not space group symmetry) provided by XRD, a comprehensive search of candidate
      framework structures leads to the identification of a small number of candidate
      structures that are each compatible with all of the experimental data. Subsequent
      refinement of the candidate structures using density functional theory
      calculations allows their evaluation and identification of "best" framework
      representations, based on their respective lattice energies and quantitative
      comparisons between experimental and calculated (29)Si isotropic chemical shifts
      and (2)J((29)Si-O-(29)Si) scalar couplings. The comprehensive analysis identifies
      three closely related and topologically equivalent framework configurations that
      are in close agreement with all experimental and theoretical structural
      constraints. The subtle differences among such similar structural models embody
      the complexity of the actual framework(s), which likely contain coexisting or
      subtle distributions of structural order that are intrinsic to the material.

PMID- 23560777
TI  - Extracellular proteases from Streptomyces phaeopurpureus ExPro138 inhibit spore
      adhesion, germination and appressorium formation in Colletotrichum coccodes.
AB  - AIM: To study the antifungal mechanism of proteases from Streptomyces
      phaeopurpureus strain ExPro138 towards Colletotrichum coccodes and to evaluate
      its utilization as biofungicide. METHODS AND RESULTS: We screened proteolytic
      Streptomyces strains from the yam rhizosphere with antifungal activity. Forty
      proteolytic Streptomyces were isolated, among which eleven isolates showed
      gelatinolytic activity and antagonistic activity on C. coccodes. Of the 11
      isolates, protease preparation from an isolate designated ExPro138 showed
      antifungal activity. 16S rDNA sequence analysis of the strain showed 99%
      similarity with Streptomyces phaeopurepureus (EU841588.1). Zymography analysis of
      the ExPro138 culture filtrate revealed that the strain produced several
      extracellular proteases. The protease preparation inhibited spore germination,
      spore adhesion to polystyrene surface and appressorium formation. Microscopic
      study of the interaction between ExPro138 and C. coccodes revealed that ExPro138
      was mycoparasitic on C. coccodes. The protease preparation also reduced
      anthracnose incidence on tomato fruits compared with untreated control.
      CONCLUSION: This study demonstrates possibility of utilizing antifungal proteases
      derived from antagonistic microbes as biofungicide. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Microbial proteases having the ability to inhibit spore adhesion and
      appressorium formation could be used to suppress infection establishment by
      foliar fungal pathogens at the initial stages of the infection process.

PMID- 23560778
TI  - How can we help children after mild traumatic brain injury?

PMID- 23560779
TI  - Assembly in vitro of Rhodococcus jostii RHA1 encapsulin and peroxidase DypB to
      form a nanocompartment.
AB  - Rhodococcus jostii RHA1 peroxidase DypB has been recently identified as a
      bacterial lignin peroxidase. The dypB gene is cotranscribed with a gene encoding
      an encapsulin protein, which has been shown in Thermotoga maritima to assemble to
      form a 60-subunit nanocompartment, and DypB contains a C-terminal sequence motif
      that is thought to target the protein to the encapsulin nanocompartment. R.
      jostii RHA1 encapsulin protein was overexpressed in R. jostii RHA1, and purified
      as a high-Mr assembly (Mr > 10(6)). The purified nanocompartment could be
      disassembled to form a low-Mr species by treatment at pH 3.0, and reassembled to
      form an assembly of similar size and shape, as assessed by dynamic light
      scattering. Recombinant DypB could be assembled in vitro with monomeric
      encapsulin to form an assembly of similar size to the encapsulin-only
      nanocompartment, as assessed by gel filtration. The assembled complex showed
      enhanced lignin degradation activity per milligram of DypB present as compared
      with native DypB, as determined with a nitrated lignin UV-visible assay method.
      The measured stoichiometry of 8.6 MUmol encapsulin/MUmol DypB in the complex was
      similar to the value of 10 predicted from the crystal structure.

PMID- 23560780
TI  - Hepatic steatosis estimated microscopically versus digital image analysis.
AB  - BACKGROUND & AIMS: Evaluate in liver biopsies: (i) interobserver agreement of
      estimates of fat proportionate area (eFPA) and steatosis grading, (ii) the
      relationship between steatosis grades and measured fat proportionate area (mFPA,
      digital image analysis), (iii) the accuracy of eFPA, (iv) to present images to
      aid standardization and accuracy of eFPA. METHODS: Twenty-one liver biopsies were
      selected from the Royal Free Hospital (RFH) histopathology archive to represent
      the full range of histopathological steatosis severity. As many non-overlapping
      fields of parenchyma as possible were photographed at *20 objective magnification
      from the biopsies (n = 651). A total of 15 sample images were selected to
      represent the range of steatosis seen. Twelve hepatopathologists from 11 sites
      worldwide independently evaluated the sample images for steatosis grade [normal
      (none)/mild/moderate/severe], and eFPA (% area of liver parenchyma occupied by
      fat). RESULTS: The hepatopathologists had good linear correlation between eFPA
      and mFPA for sample images (r = 0.924, P < .001) and excellent concordance (kappa
      = 0.91, P < 0.001). Interobserver concordance of steatosis grade showed
      'substantial agreement' (kappa = 0.64). There was significant difference between
      eFPA and mFPA in the sample images for mild, moderate and severe steatosis (P =
      0.024, P < 0.001, P < 0.001 respectively): the observers consistently over
      estimated the eFPA. CONCLUSION: Hepatopathologists showed 'excellent'
      interobserver agreement in eFPA and 'substantial' agreement in assigning
      steatosis grade (precision was high). However, compared with mFPA, eFPA was
      inaccurate. eFPA systematically exceeds mFPA; generally the overestimation
      increases with severity of steatosis. Considering that non-invasive technologies
      for estimating liver fat utilize histopathology as reference, such assessments
      would benefit from quantitative validation of visually estimated microscopic
      liver fat percentages.

PMID- 23560781
TI  - [Pioneer Argentine mycologists in the study of histoplasmosis].

PMID- 23560782
TI  - Novel organic solvent-tolerant esterase isolated by metagenomics: insights into
      the lipase/esterase classification.
AB  - in order to isolate novel organic solvent-tolerant (OST) lipases, a metagenomic
      library was built using DNA derived from a temperate forest soil sample. A two
      step activity-based screening allowed the isolation of a lipolytic clone active
      in the presence of organic solvents. Sequencing of the plasmid pRBest recovered
      from the positive clone revealed the presence of a putative lipase/esterase
      encoding gene. The deduced amino acid sequence (RBest1) contains the conserved
      lipolytic enzyme signature and is related to the previously described OST lipase
      from Lysinibacillus sphaericus 205y, which is the sole studied prokaryotic enzyme
      belonging to the 4.4 alpha/beta hydrolase subgroup (abH04.04). Both in vivo and
      in vitro studies of the substrate specificity of RBest1, using triacylglycerols
      or nitrophenyl-esters, respectively, revealed that the enzyme is highly specific
      for butyrate (C4) compounds, behaving as an esterase rather than a lipase. The
      RBest1 esterase was purified and biochemically characterized. The optimal
      esterase activity was observed at pH 6.5 and at temperatures ranging from 38 to
      45  degrees C. Enzymatic activity, determined by hydrolysis of p-nitrophenyl
      esters, was found to be affected by the presence of different miscible and non
      miscible organic solvents, and salts. Noteworthy, RBest1 remains significantly
      active at high ionic strength. These findings suggest that RBest1 possesses the
      ability of OST enzymes to molecular adaptation in the presence of organic
      compounds and resistance of halophilic proteins.

PMID- 23560783
TI  - [Immune response and reproductive consequences in experimentally infected ewes
      with Brucella ovis during late pregnancy].
AB  - Ovine brucellosis by Brucella ovis is a highly prevalent disease in Argentina.
      This study aimed to evaluate the pathogenicity of B. ovis and the serological
      response in ewes during late pregnancy and in their offspring. Six adult ewes
      were distributed in two groupsG1 (pregnant females, n = 4) and G2 (nonpregnant
      females, n = 2). Three pregnant ewes at 15 days prepartum and one nonpregnant eve
      were inoculated with B. ovis. Sera of sheep and their offspring were analyzed by
      different serological tests. Samples of cervicovaginal mucus, placenta and milk
      were studied by bacteriology. A Brucella genus-specific PCR assay was carried out
      in placenta and milk samples. Placenta samples were hystopathologically
      processed. g1 females gave birth to live lambs, but one died hours postpartum.
      Serological techniques employed detected antibodies in serum of inoculated
      pregnant animal 5 days postchallenge. sera of female controls G1 and G2 remained
      negative throughout the study. Cervicovaginal mucus of infected ewes in G1 and G2
      yielded negative results to bacteriology, but B. ovis was isolated from milk. The
      PCR assay was positive for the placenta and milk from inoculated pregnant ewes.
      Histopathology revealed necrotic suppurative placentitis in one placenta.
      However, although results demonstrated that B. ovis can invade the placenta and
      mammary gland, this bacterium did not cause abortion when it was inoculated
      intravenously at 15 days prepartum. B. ovis infection induced an early humoral
      response in pregnant ewes, but their lambs remained seronegative, indicating that
      there was no transfer of antibodies in infancy. Placenta colonization and milk
      excretion of B. ovis involves a potential source of infection for lambs, which
      could play a role as latent carriers of infection.

PMID- 23560784
TI  - Association between embB mutations and ethambutol resistance in Mycobacterium
      tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns
      and problems.
AB  - The relation of ethambutol resistance to embB mutations remains unclear, and
      there are no reports on ethambutol resistance from the caribbean. We examined the
      sequence of embB in 57 distinct Multi-Drug Resistant (MDR) and non-MDR strains of
      Mycobacterium tuberculosis, mostly from Cuba and the Dominican Republic. embB306
      codon mutations were found exclusively in MDR-TB, but in both ethambutol
      sensitive and resistant strains. Valine substitutions predominated in ethambutol
      resistant strains, while isoleucine replacements were more common in sensitive
      strains. Three ethambutol resistant MDR strains without embB306 substitutions had
      replacements in embB406 or embB497, but these were also found in ethambutol
      sensitive MDR strains. The results confirm previous findings that amino acid
      substitutions in EmbB306, EmbB406 and EmbB497 are found only in MDR-TB strains
      but in both phenotypically resistant and sensitive strains. One ethambutol
      resistant non-MDR strain did not have any embB mutation suggesting that other
      undefined mutations can also confer ethambutol resistance.

PMID- 23560785
TI  - Serotype distribution of pneumococci isolated from pediatric patients with acute
      otitis media and invasive infections, and potential coverage of pneumococcal
      conjugated vaccines.
AB  - A 16-month prospective, descriptive study was conducted on pneumococcal serotype
      distribution isolated from children with acute otitis media (AOM) and invasive
      infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first
      episode of AOM were included. Bacterial pathogens (N = 326) were isolated from
      the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were
      identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM
      and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine
      would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively;
      it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus
      protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with
      PCV13. However, differences in the prevention of INV were crucial for the
      decision to include the 13-valent vaccine in the national calendar for children
      less than two years old in Argentina.

PMID- 23560786
TI  - Detection of reactive canines to Leptospira in Campeche City, Mexico.
AB  - Leptospira reactivity in stray and household dogs in Campeche as well as
      associated risk factors to the seropositivity in household dogs have been herein
      determined. The survey included 323 dogs, 142 of which were stray dogs and 181
      household dogs. Nine Leptospira interrogans serovars were tested by the
      microagglutination test. Reactivity was 21.3 % (69/323), 17.2 % corresponded to
      household dogs and 26.7 % to stray dogs. Leptospira Canicola (29 %), Leptospira
      Hardjo (22.58 %), and Leptospira Icterohaemorrhagiae (16.12 %) were the most
      common serovars reacting against the serum of household animals, while Leptospira
      Canicola (15.78 %), Leptospira icterohaemorrhagiae (13.15 %), and Leptospira
      Pomona (7.89 %) were those reacting in stray dogs. Results showed that all dogs
      have been in contact with different Leptospira serovars and outdoor exposure is
      the main infection risk factor.

PMID- 23560787
TI  - [Molecular detection and genotypification of Helicobacter pylori in gastric
      biopsies from symptomatic adult patients in Santa Fe, Argentina].
AB  - Our goals were: a) to detect Helicobacter pylori in gastric biopsies of
      symptomatic adults by PCR, b) to detect the presence of the cagA gene as well as
      of the allelic variants of the vacA gene, and c) to correlate genotypes with the
      endoscopic diagnoses. H. pylori was detected in 81 % (39/48) of patients by
      nested PCR for hsp60. The presence of cagA was detected in 15/22 of samples and
      vacA s1 - m1 was the most frequent allelic combination (15/22). Gastritis, the
      most frequent diagnosis, was associated with genotype cagA+ in 10/13 of patients.
      In this group, 9/13 showed the allelic variant vacA s1- m1. The variant vacA s2 -
      m2 was detected in 3/3 of gastritis cases by H. pylori with the cagA- genotype.
      These results are the first reported in our region and provide data of
      epidemiological interest.

PMID- 23560788
TI  - [Bacterial isolates from respiratory samples of pediatric patients with cystic
      fibrosis and their distribution by ages].
AB  - The bacterial isolates from respiratory samples of 50 pediatric patients with
      cystic fibrosis, their distribution by ages and antimicrobial resistance pattern
      as well as the intermittence of isolations and coinfections, were investigated.
      Staphylococcus aureus was isolated in 72 % of patients, followed by Pseudomonas
      aeruginosa (58 %), Haemophilus. influenzae (56 %), and the Burkholderia cepacia
      complex (12 %). The frequency of resistance of P. aeruginosa isolates to beta
      lactam antibiotics was low (13.8 %). Fifty percent of S. aureus isolates was
      methicillin-resistant, and 57.1 % of H. influenza was ampicillin resistant due to
      beta-lactamase production. In children under 4 years-old, S. aureus was
      predominant, followed by P. aeruginosa and H. influenzae. This order of
      predominance was observed in all the groups studied, except in that of children
      between 10 and 14 years-old. Stenotrophomonas maltophilia and Achromobacter
      xylosoxidans isolates were intermittent and accompanied by other microorganisms.
      Finally, we observed a great variety of bacterial species, which imposes
      stringent performance requirements for microbiological studies in all respiratory
      samples of these patients.

PMID- 23560789
TI  - [Brucella canis endocarditis: first documented case in Argentina].
AB  - We herein present the case of an adult male patient who consulted for lower
      extremity edema, a 2- month history of fever and oppressive chest pain radiating
      to the left arm. He referred neither contact with breeding animals nor
      consumption of unpasteurized dairy products. A diagnosis of endocarditis was
      confirmed by cardiac studies. Since the empirical treatment with cephalotin,
      ampicillin and gentamicin failed, the patient underwent aortic valve replacement.
      A total of four blood cultures were positive with a gram-negative rod. Bacterial
      identification was performed using the API 20 NE technique (bioMerieux), the
      Phoenix automated method (BD) and conventional biochemical tests which were
      unable to classify the isolate as to genus and species. The strain was sent to
      the INEI-ANLIS "Dr. Carlos G. Malbran" where it was identified as Brucella canis.
      The antimicrobial treatment was switched to doxycycline, rifampicin and
      trimethoprim-sulfamethoxazole with good evolution of the patient. The clinical
      significance of this case report lies in the possible failure of the empiric
      antibiotic therapy administered for endocarditis, since B. canis did not respond
      to the conventional antimicrobial treatment for this pathology.

PMID- 23560791
TI  - Antimicrobial susceptibility profile of Pseudomonas spp. isolated from a swine
      slaughterhouse in Dourados, Mato Grosso do Sul State, Brazil.
AB  - The present work sought to detect the presence of Pseudomonas spp. at different
      stages of an effluent treatment plant using the Australian system of
      stabilization ponds, and to determine the susceptibility of those isolates to
      different antimicrobials. Thirty-four isolates of Pseudomonas spp. derived from
      effluent treatment station water samples were collected near the transfer ducts
      between the ponds in November/2008 and december/2009. Among the Pseudomonas spp.
      isolates, 47.05 % showed susceptibility to all antimicrobials tested, 20.58 %
      were resistant to cefepime, and 24 % showed intermediate resistance to
      streptomycin. No Pseudomonas spp. isolates were found in the final pond, or in
      post-treatment effluents. The Pseudomonas spp. isolates did not exhibit
      multiresistance to the antimicrobials tested.

PMID- 23560790
TI  - [Neisseria gonorrhoeae identification. Usefulness of the Vitek 2C NH card].
AB  - A total of 115 unique clinical isolates of Neisseria gonorrhoeae and 54 strains
      of other genera and species included in the database of the NH card were tested
      by the Vitek 2C System (bioMerieux, Marcy L'Etoile, Francia). The gonoccocal
      isolates had been previously identified by conventional biochemical tests and by
      the latex agglutination test with monoclonal antibodies using the Phadebact
      Monoclonal GC Test (Bactus AB, Sweden). The NH card correctly identified 111
      (96.5 %) strains of 115 isolates; one strain was identified with low
      discriminatory power (0.86 %), one (0.86 %) was misidentified (as Neisseria
      meningitidis) whereas the other two (1.7 %) remained unidentified. The NH card
      for N. gonorrhoeae identification provided 100 % specificity. The results were
      available within 6 hours. The NH card could be considered a reliable and useful
      tool for routine use in Neisseria gonorrhoeae identification.

PMID- 23560792
TI  - [Soft tissue infection by probable community-acquired methicillin-resistant
      Staphylococcus aureus].

PMID- 23560793
TI  - Rate-limited electroless gold thin film growth: a real-time study.
AB  - Time-resolved, in situ spectroscopy of electroless (EL) gold (Au) films combined
      with electron microscopy showed that the deposition rate increased up to two-fold
      on surfaces swept by the bulk flow of adjacent fluid at Reynolds numbers less
      than 1.0, compared to batch immersion. Deposition rates from 5.0 to 9.0 nm/min
      and thicknesses of the EL Au film from 20 to 100 nm, respectively, increased
      predictably with flow rate at conditions when the deposition was limited
      primarily by Fickian diffusion. Time-frames were identified for metal island
      nucleation, growth, and subsequent film development during EL Au deposition by
      real-time UV-visible spectroscopy of photoluminescence (PL) and surface plasmon
      features of nanoscale metal deposits. Film thicknesses measured by scanning
      electron microscopy and X-ray photoelectron spectroscopy paired with real-time
      optical spectroscopy of kinetic aspects of plasmon and PL optical features
      indicated that Au film deposition on surfaces swept by a steady flow of adjacent
      fluid can be primarily diffusion limited.

PMID- 23560795
TI  - Complications and subsequent removal of retained shunt hardware after endoscopic
      third ventriculostomy: case series.
AB  - This case series highlights multiple complications and subsequent removal of
      retained shunt hardware in pediatric patients after successful endoscopic third
      ventriculostomy (ETV). Removal or retention of existing shunt hardware following
      ETV represents an important dilemma. Prior studies have reported infections and
      organ perforation related to nonfunctioning shunts but none in the context of
      successful ETV. Data obtained in 3 children with hydrocephalus treated at the
      authors' institution were retrospectively reviewed after the patients experienced
      complications due to retained shunt hardware following ETV. Etiologies of
      hydrocephalus included tectal glioma and intraventricular hemorrhage. All 3
      patients had a history of multiple shunt revisions and underwent urgent ETV in
      the setting of a shunt malfunction. In each case, the entire shunt system was
      left in situ, but it became the source of subsequent complications. Two of the 3
      patients presented with the shunt infected by gram-negative bacilli 10 days and
      4.5 months postoperatively, respectively. The remaining patient experienced wound
      dehiscence over the shunt valve 4.5 months after ETV. In all patients, the
      complications were managed successfully by removing the shunt hardware. None of
      the patients required repeat shunt insertion from the time of removal throughout
      the follow-up period (mean 24 months, range 9-36 months). During the study
      period, a total of 6 patients with indwelling shunt hardware underwent ETV with
      the expectation of being shunt independent. Among these 6 patients, 3 experienced
      no complications from the retained hardware whereas 3 patients (50%) ultimately
      experienced adverse consequences related to retained hardware. This case series
      illustrates complications involving retained shunt hardware after successful ETV.
      These examples support consideration of shunt removal at the time of ETV in the
      appropriate context.

PMID- 23560794
TI  - Identifying concealment-related responses in the concealed information test.
AB  - The concealed information test (CIT) assesses an examinee's recognition of a
      crime-relevant item using physiological measures. However, a guilty examinee not
      only recognizes the crime-relevant item but also conceals the recognition
      intentionally. In this study, we attempted to identify the effect of concealing
      the recognition on event-related potentials and autonomic responses. After
      committing a mock theft of two items, 30 participants received two CITs: one for
      an item that they had to conceal, and the other for an item that they had
      disclosed. N2, P3, heart rate, skin conductance, and cutaneous blood flow
      differed between crime-relevant and irrelevant items in both CITs. In contrast,
      late positive potential and respiration differed between crime-relevant and
      irrelevant items only when the examinee needed to conceal. The former measures
      appear to be related to orienting process, whereas the latter to controlled
      process related to concealment.

PMID- 23560796
TI  - Inverse neighboring group participation: explanation of an unusual S->N alkyl
      migration of isothiuronium salts containing a lactone group.
AB  - A detailed experimental and DFT study of the S to N alkyl migration of
      substituted S-(1(3H)-isobenzofuranon-3-yl)isothiuronium bromide to N,N'-dimethyl
      N-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thiourea provided evidence for the
      existence of an unusual double displacement mechanism involving two consecutive
      back-side S(N)2 reactions where a carboxylate anion has a crucial role both as a
      leaving group as well as an internal nucleophile. The thiazetidine zwitterionic
      species that is involved in this mechanism as an intermediate was characterized
      by infrared multiphoton dissociation spectroscopy and was trapped with methyl
      iodide. It was found that the intermediate has a structure of a free ion pair.
      The double-displacement mechanism can be considered as a new type of inverse
      lactone neighboring group participation.

PMID- 23560797
TI  - Cone-beam computed tomographic analysis of sinus membrane thickness, ostium
      patency, and residual ridge heights in the posterior maxilla: implications for
      sinus floor elevation.
AB  - OBJECTIVE: To determine, using cone-beam computed tomography (CBCT), the residual
      ridge height (RRH), sinus floor membrane thickness (MT), and ostium patency (OP)
      in patients being evaluated for implant placement in the posterior maxilla.
      MATERIALS AND METHODS: CBCT scans of 128 patients (199 sinuses) with >=1 missing
      teeth in the posterior maxilla were examined. RRH and MT corresponding to each
      edentulous site were measured. MT >2 mm was considered pathological and
      categorized by degree of thickening (2-5, 5-10 mm, and >10 mm). Mucosal
      appearance was classified as "normal", "flat thickening", or "polypoid
      thickening", and OP was classified as "patent" or "obstructed". Descriptive and
      bivariate statistical analyses were performed. RESULTS: MT >2 mm was observed in
      60.6% patients and 53.6% sinuses. Flat and polypoid mucosal thickening had a
      prevalence of 38.1% and 15.5%, respectively. RRH <=4 mm was observed in 46.9% and
      48.9% of edentulous first and second molar sites, respectively. Ostium
      obstruction was observed in 13.1% sinuses and was associated with MT of 2-5 mm
      (6.7%), 5-10 mm (24%), and >10 mm (35.3%, P < 0.001). Polypoid mucosal lesions
      were more frequently associated with ostium obstruction than flat thickenings
      (26.7% vs. 17.6%, P < 0.001). CONCLUSION: Thickened sinus membranes (>2 mm) and
      reduced residual ridge heights (<=4 mm) were highly prevalent in this sample of
      patients with missing posterior maxillary teeth. Membrane thickening >5 mm,
      especially of a polypoid type, is associated with an increased risk for ostium
      obstruction. In the presence of these findings, an ENT referral may be beneficial
      prior to implant-related sinus floor elevation.

PMID- 23560798
TI  - Disease spread models to estimate highly uncertain emerging diseases losses for
      animal agriculture insurance policies: an application to the U.S. farm-raised
      catfish industry.
AB  - Emerging diseases (ED) can have devastating effects on agriculture. Consequently,
      agricultural insurance for ED can develop if basic insurability criteria are met,
      including the capability to estimate the severity of ED outbreaks with associated
      uncertainty. The U.S. farm-raised channel catfish (Ictalurus punctatus) industry
      was used to evaluate the feasibility of using a disease spread simulation
      modeling framework to estimate the potential losses from new ED for agricultural
      insurance purposes. Two stochastic models were used to simulate the spread of ED
      between and within channel catfish ponds in Mississippi (MS) under high, medium,
      and low disease impact scenarios. The mean (95% prediction interval (PI))
      proportion of ponds infected within disease-impacted farms was 7.6% (3.8%,
      22.8%), 24.5% (3.8%, 72.0%), and 45.6% (4.0%, 92.3%), and the mean (95% PI)
      proportion of fish mortalities in ponds affected by the disease was 9.8% (1.4%,
      26.7%), 49.2% (4.7%, 60.7%), and 88.3% (85.9%, 90.5%) for the low, medium, and
      high impact scenarios, respectively. The farm-level mortality losses from an ED
      were up to 40.3% of the total farm inventory and can be used for insurance
      premium rate development. Disease spread modeling provides a systematic way to
      organize the current knowledge on the ED perils and, ultimately, use this
      information to help develop actuarially sound agricultural insurance policies and
      premiums. However, the estimates obtained will include a large amount of
      uncertainty driven by the stochastic nature of disease outbreaks, by the
      uncertainty in the frequency of future ED occurrences, and by the often sparse
      data available from past outbreaks. 

PMID- 23560799
TI  - ABCA8 stimulates sphingomyelin production in oligodendrocytes.
AB  - Members of the ABCA (ATP-binding cassette subfamily A) family are characterized
      by their ability to transport lipids across cellular membranes and regulate lipid
      homoeostasis in the brain and peripheral tissues. ABCA8 is a little-known member
      of this subfamily that was originally cloned from human brain libraries and has
      no known function. In an effort to elucidate the role of ABCA8 in the brain we
      first undertook a comprehensive analysis of its expression in the human brain.
      ABCA8 was differentially expressed in multiple regions of adult human brains with
      significantly higher expression in oligodendrocyte-enriched white matter regions
      compared with grey matter cortical regions. We then assessed the impact of ABCA8
      on sphingomyelin production in oligodendrocyte and showed that ABCA8 was able to
      significantly stimulate both sphingomyelin synthase 1 expression and
      sphingomyelin production. Furthermore, ABCA8 expression in the prefrontal cortex
      across the human life span correlated strongly with age-associated myelination,
      and the myelinating gene p25alpha was significantly up-regulated with ABCA8. The
      present study represents the first extensive expression and functional study of
      ABCA8 in the human brain and the results strongly suggest that ABCA8 regulates
      lipid metabolism in oligodendrocytes and potentially plays a role in myelin
      formation and maintenance.

PMID- 23560800
TI  - Lipid bilayer membrane affinity rationalizes inhibition of lipid peroxidation by
      a natural lignan antioxidant.
AB  - Lipid peroxidation is a degenerative oxidative process that modifies the
      structure of membranes, influencing their biological functions. Lignans, natural
      polyphenolic antioxidants widely distributed in plants, can prevent this membrane
      damage by free-radical scavenging. Here, we rationalize the difference in lipid
      peroxidation inhibition activity of argenteane, a natural dilignan isolated from
      wild nutmeg, and 3,3'-dimethoxy-1,1'-biphenyl-2,2'-diol, which represents the
      central part of argenteane responsible for its antioxidant activity. Although
      both compounds have the same capacity to scavenge free radicals, argenteane is a
      more active inhibitor of lipid peroxidation. We show that both compounds
      penetrate into DOPC and PLPC lipid bilayers and adopt similar positions and
      orientations, which therefore does not explain the difference in their lipid
      peroxidation inhibition activity. However, free energy profiles indicate that
      argenteane has a significantly higher affinity to the lipid bilayer, and thus a
      higher effective concentration to scavenge radicals formed during lipid
      peroxidation. This finding explains the higher activity of argenteane to inhibit
      lipid peroxidation.

PMID- 23560801
TI  - Regulation of haemolysin (VvhA) production by ferric uptake regulator (Fur) in
      Vibrio vulnificus: repression of vvhA transcription by Fur and proteolysis of
      VvhA by Fur-repressive exoproteases.
AB  - VvhA produced by Vibrio vulnificus exhibits cytolytic activity to human cells
      including erythrocytes. Since haemolysis by VvhA may provide iron for bacterial
      growth and pathogenicity, we investigated the expression of VvhA to elucidate the
      regulatory roles of Fur, a major transcription factor controlling iron
      homeostasis. Fur repressed the transcription of vvhBA operon via binding to the
      promoter region. However, haemolysin content and haemolytic activity were lowered
      in cell-free supernatant of fur mutant. This discrepancy between the levels of
      vvhA transcript and VvhA protein in fur mutant was caused by exoproteolytic
      activities of the elastase VvpE and another metalloprotease VvpM, which were also
      regulated by Fur. vvpE gene expression was repressed by Fur via binding to the
      Fur-box homologous region. Regulation of VvpM expression by Fur did not occur at
      the level of vvpM transcription. In vitro proteolysis assays showed that both
      proteases efficiently degraded VvhA. In addition, the extracellular levels of
      VvhA were higher in culture supernatants of vvpE or vvpM mutants than in the wild
      type. Thus this study demonstrates that Fur regulates haemolysin production at
      the transcription level of the vvhBA operon and at the post-translation level by
      regulating the expressions of two VvhA-degrading exoproteases, VvpE and VvpM.

PMID- 23560802
TI  - A novel approach to treatment of lymphangiosarcoma in a boxer dog.
AB  - A five-year-old female boxer presented with a swelling in the area of the caudal
      mammary gland. The mass was surgically excised and histopathological examination
      revealed a poorly demarcated lesion, extending into mammary tissue and
      infiltrating the sinuses of adjacent lymph nodes. The diagnosis was
      lymphangiosarcoma. Full blood work, thoracic radiographs, abdominal and scar
      ultrasound were unremarkable, apart from possible inflammatory reactions in the
      latter and reactive/metastatic changes in inguinal lymph nodes. Doxorubicin
      treatment resulted in a 6-month recurrence free interval. At relapse, the dog was
      treated with metronomic chemotherapy using chlorambucil and meloxicam, which
      failed to adequately control the disease. Toceranib phosphate was introduced and
      resulted in almost complete regression of the mass, leaving just a skin plaque.
      To the authors' knowledge this is the first report describing the use of two
      novel therapeutic approaches to treat canine lymphangiosarcoma that resulted in a
      higher than previously described survival time.

PMID- 23560803
TI  - Infant feeding practices in the first 24-48 h of life in healthy term infants.
AB  - AIM: To examine in-hospital infant feeding practices, focusing on initiation and
      prevalence of breastmilk expression and to describe the proportion of women
      having a breast pump immediately after birth. METHODS: Postpartum women were
      recruited from three hospitals in Melbourne, Australia, between 2009 and 2011.
      INCLUSION CRITERIA: having had a healthy singleton term infant, intending to
      breastfeed and fluency in English. Data were collected using a structured
      questionnaire. RESULTS: Just over 1000 women were recruited at 24-48 h
      postpartum; 50% were primiparous. Forty-seven per cent of infants had been fully
      breastfeeding at the breast from birth, and another 47% had received at least
      some expressed breastmilk. Forty per cent of first-time mothers reported having
      had a problem breastfeeding, and 46% already had a breast pump prior to the birth
      of their infant. CONCLUSIONS: Early breastfeeding problems were common, and less
      than half the infants had fed only at the breast in the first days of life. Given
      the normalization of breastmilk expression, more evidence is needed regarding the
      impact of expressing on duration of breastmilk feeding and maternal health
      outcomes.

PMID- 23560804
TI  - Dibenzodiazepine derivative quetiapine- and olanzapine-induced chronic
      interstitial nephritis.
AB  - The dibenzodiazepine derivative is a so-called "atypical" or second-generation
      antipsychotic that is widely regarded as one of the most effective drug
      treatments for schizophrenia and depression. Quetiapine and olanzapine are novel
      atypical antipsychotic agents that possess much improved tolerability. To the
      best of our knowledge, FDA has reported three cases of olanzapine-induced
      interstitial nephritis. Yet there have been no known clinical reports that
      associate quetiapine treatment with chronic interstitial nephritis (CIN). Here,
      we report the occurrence of CIN in the presence of edema during quetiapine and
      olanzapine therapy.

PMID- 23560805
TI  - Lysine-based surfactants in nanovesicle formulations: the role of cationic charge
      position and hydrophobicity in in vitro cytotoxicity and intracellular delivery.
AB  - Understanding nanomaterial interactions within cells is of increasing importance
      for assessing their toxicity and cellular transport. Here, the authors developed
      nanovesicles containing bioactive cationic lysine-based amphiphiles and assessed
      whether these cationic compounds increase the likelihood of intracellular
      delivery and modulate toxicity. Different cytotoxic responses were found among
      the formulations, depending on surfactant, cell line and endpoint assayed. The
      induction of mitochondrial dysfunction, oxidative stress and apoptosis were the
      general mechanisms underlying cytotoxicity. Fluorescence microscopy analysis
      demonstrated that nanovesicles were internalised by HeLa cells and evidenced that
      their ability to release endocytosed materials into cell cytoplasm depends on the
      structural parameters of amphiphiles. The cationic charge position and
      hydrophobicity of surfactants determine the nanovesicle interactions within the
      cell and, thus, the resulting toxicity and intracellular behaviour after cell
      uptake of the nanomaterial. The insights into some toxicity mechanisms of these
      new nanomaterials contribute in reducing the uncertainty surrounding their
      potential health hazards.

PMID- 23560806
TI  - Penicillium oxalicum reduces the number of cysts and juveniles of potato cyst
      nematodes.
AB  - AIM: To test the biocontrol potential of Penicillium oxalicum, a biocontrol agent
      against fungal diseases and against the potato cyst nematodes (PCNs), Globodera
      pallida and Globodera rostochiensis. METHODS AND RESULTS: We tested the effect of
      P. oxalicum on the nematode cysts under laboratory conditions or in soil
      microcosms. A reduction in the rate of G. pallida juveniles hatching by P.
      oxalicum was observed when root diffusates from the 'Monalisa' and the 'Desiree'
      potato cultivar were used (98.6 and 74.1% reduction, respectively). However, the
      rate of G. pallida juveniles hatching was not significantly reduced when root
      diffusates from the 'San Pedro' tomato cultivar were used. Penicillium oxalicum
      also significantly reduced the ability of the G. rostochiensis juveniles to hatch
      (30.9% reduction) when root diffusates of the 'Desiree' potato cultivars were
      used. Penicillium oxalicum treatment of the soil significantly reduced the number
      of G. pallida cysts that were recovered from the soil of each pot that contained
      the 'Desiree' potato cultivar. CONCLUSIONS: Our results show that P. oxalicum is
      a potential biocontrol inoculant for protecting potato crops against PCNs.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Penicillium oxalicum has potential to be
      used in order to reduce PCNs.

PMID- 23560807
TI  - Current pharmacotherapeutical options for the prevention of kidney transplant
      rejection.
AB  - INTRODUCTION: Advances in immunosuppression and medical care over the past years
      resulted in better short- and long-term graft survival following kidney
      transplantation. Novel potent immunosuppressive agents, combinations of proven
      substances and the steadily expanding knowledge on the pathophysiology of kidney
      transplant rejection allows the extension of donor and recipient criteria,
      including the usage of organs from ABO-incompatible and crossmatch-positive
      donors, to overcome the increasing problem of organ shortage. AREAS COVERED:
      Immunosuppressive regimens for the prevention of kidney transplant rejections
      with a focus on regimens aiming at calcineurin inhibitor or steroid minimization,
      withdrawal or avoidance. Prevention of antibody-mediated rejections in standard
      risk and sensitized recipients, as well as newly introduced immunosuppressive
      substances are covered. EXPERT OPINION: Currently applied immunosuppressive
      regimens are associated with excellent short-term graft survival. However, the
      long-term outcomes of different regimens substantially differ with regard to
      potential side effects, graft function, rejection and sensitization rates. The
      adverse effects of effective immunosuppression must carefully be balanced against
      the benefit, e.g., prevention of the development of donor-specific human
      leukocyte antigen antibodies and chronic (antibody-mediated) rejection. The
      choice of the appropriate immunosuppressive regimen requires clinical experience
      and careful consideration of recipient and transplant characteristics to achieve
      an optimal long-term graft survival.

PMID- 23560808
TI  - Role of infected grandmothers in transmission of Helicobacter pylori to children
      in a Japanese rural town.
AB  - AIM: Although the prevalence of Helicobacter pylori (H. pylori) increases with
      age and the main period of acquisition is childhood, the route of transmission of
      H. pylori infection remains unclear. This study aims to evaluate the relationship
      between prevalence of children and grandparents. METHODS: A total of 838
      consecutive children who attended the Urita clinic and whose blood was taken for
      work up were enrolled in the present study. They were 449 boys and 389 girls,
      with a mean age of 12.4 years. H. pylori serology of their family members who
      were living together in one house was picked up to analyse intra-familial
      clustering of H. pylori infection. The family members of these children consisted
      of 448 fathers, 597 mothers, 205 grandfathers, 361 grandmothers and 589 siblings.
      RESULTS: The seropositive rates of mothers, grandmother and siblings in
      seropositive children were significantly higher than those in seronegative
      children. H. pylori infection in mothers and grandmothers was a marked risk
      factor for infection in the index children. Larger family size was not a risk
      factor for H. pylori infection. In contrast, having an infected father or
      grandfather was not an independent predictor for children infection. CONCLUSIONS:
      Our data demonstrate that not only mother-to-child transmission but also
      grandmother-to-child transmission is an important mechanism for the spread of H.
      pylori in a three-generation household.

PMID- 23560809
TI  - Changed terms for drug payment influenced GPs' diagnoses and prescribing practice
      for inhaled corticosteroids.
AB  - BACKGROUND: Inhaled glucocorticosteroids (ICS) are first-line anti-inflammatory
      treatment in asthma, but not in chronic obstructive pulmonary disease (COPD). To
      restrict ICS use in COPD to cases of severe disease, new terms for reimbursement
      of drug costs were introduced in Norway in 2006, requiring a diagnosis of COPD to
      be verified by spirometry. OBJECTIVES: To describe how GPs' diagnoses and
      treatment of patients who used ICS before 2006 changed after a reassessment of
      the patients that included spirometry. METHODS: From the shared electronic
      patient record system in one group practice, patients >= 50 years prescribed ICS
      (including in combination with long-acting beta2-agonists) during the previous
      year were identified and invited to a tailored consultation including spirometry
      to assure the quality of diagnosis and treatment. GPs' diagnoses and ICS
      prescribing patterns after this reassessment were recorded, retrospectively.
      RESULTS: Of 164 patients identified, 112 were included. Post-bronchodilator
      spirometry showed airflow limitation indicating COPD in 55 patients. Of the 57
      remaining patients, five had a positive reversibility test. The number of
      patients diagnosed with asthma increased (from 25 to 62) after the reassessment.
      A diagnosis of COPD was also more frequently used, whereas fewer patients had
      other pulmonary diagnoses. ICS was discontinued in 31 patients; 20 with mild to
      moderate COPD and 11 with normal spirometry. CONCLUSION: Altered reimbursement
      terms for ICS changed GPs' diagnostic practice in a way that made the diagnoses
      better fit with the treatment given, but over-diagnosis of asthma could not be
      excluded. Spirometry was useful for identifying ICS overuse.

PMID- 23560810
TI  - Effectiveness and cost-effectiveness of rehabilitation after lumbar disc surgery
      (REALISE): design of a randomised controlled trial.
AB  - BACKGROUND: Patients who undergo lumbar disc surgery for herniated discs, are
      advocated two different postoperative management strategies: a watchful waiting
      policy, or referral for rehabilitation immediately after discharge from the
      hospital. A direct comparison of the effectiveness and cost-effectiveness of
      these two strategies is lacking. METHODS/DESIGN: A randomised controlled trial
      will be conducted with an economic evaluation alongside to assess the (cost-)
      effectiveness of rehabilitation after lumbar disc surgery. Two hundred patients
      aged 18-70 years with a clear indication for lumbar disc surgery of a single
      level herniated disc will be recruited and randomly assigned to either a watchful
      waiting policy for first six weeks or exercise therapy starting immediately after
      discharge from the hospital. Exercise therapy will focus on resumption of
      activities of daily living and return to work. Therapists will tailor the
      intervention to the individual patient's needs. All patients will be followed up
      by the neurosurgeon six weeks postoperatively. Main outcome measures are:
      functional status, pain intensity and global perceived recovery. Questionnaires
      will be completed preoperatively and at 3, 6, 9, 12 and 26 weeks after surgery.
      Data will be analysed according to the intention-to-treat principle, using a
      linear mixed model for continuous outcomes and a generalised mixed model for
      dichotomous outcomes. The economic evaluation will be performed from a societal
      perspective. DISCUSSION: The results of this trial may lead to a more consistent
      postoperative strategy for patients who will undergo lumbar disc surgery. TRIAL
      REGISTRATION: Netherlands Trial Register: NTR3156.

PMID- 23560811
TI  - Characteristics of post-traumatic headaches in children following mild traumatic
      brain injury and their response to treatment: a prospective cohort.
AB  - AIM: Post-traumatic headaches (PTHs) following mild traumatic brain injury (mTBI)
      are common; however, few studies have examined the characteristics of PTHs or
      their response to treatment. The aims of this study were (1) to describe the
      clinical characteristics of PTH in a prospective cohort of children presenting to
      a paediatric emergency department with mTBI, and (2) to evaluate the response of
      PTH to treatment. METHOD: The emergency department cohort was obtained from a
      prospective longitudinal cohort study of symptoms following mTBI (n=670; 385
      males, 285 females) and a comparison group of children with extracranial injury
      (n=120; 61 males, 59 females). A retrospective chart review of a separate cohort
      of children from a brain injury clinic (the treatment cohort) treated for PTH was
      performed (n=44; 29 females, 15 males; mean age 14 y 1 mo, SD 3 y 1 mo). The
      median time since injury was 6.9 months (range 1-29 mo). The mean follow-up
      interval after treatment started was 5.5 weeks (SD 4.3 wks). RESULTS: Among the
      emergency department cohort (n=39; 20 males, 19 females; mean age 11 y 1 mo, SD 4
      y 3 mo) 11% of children were symptomatic with PTHs at a mean of 15.8 days (SD
      11.6d) post injury. Three months post injury, 7.8% of children complained of
      headaches; of those, 56% had pre-existing headaches and 18% had experienced
      migraine before the injury. Although headache type varied, 55% met the criteria
      for migraine. A family or past medical history of migraine was present in 82% of
      cases. Among the treatment cohort, medications included amitriptyline,
      flunarizine, topiramate, and melatonin, with an overall response rate of 64%.
      CONCLUSION: This is the first prospective cohort study to describe the clinical
      characteristics of PTHs following mTBI in children. Migraine was the most common
      headache type seen; other headaches included tension-type, cervicogenic, and
      occipital neuralgias, and 64% responded to treatment. Referral to a headache
      specialist should be considered, especially when the features are not typical of
      one of the primary headache disorders.

PMID- 23560813
TI  - Human periodontal ligament fibroblast responses to compression in chronic
      periodontitis.
AB  - AIM: Test whether human periodontal ligament fibroblasts (PDLFs) retain
      homeostatic responses to a physiological compressive force during chronic
      periodontitis. MATERIAL AND METHODS: Six cell lines were established from
      periodontally healthy individuals (H-PDLFs) and another six were cultured from
      patients diagnosed with chronic periodontitis (D-PDLFs). Compressive force at 150
      psi was applied to H-and D-PDLFs for 3 h on 2 consecutive days. After
      compression, comparisons between H-and D-PDLFs were performed by gene expression
      analysis of IL-6, proteases and 84 inflammation-related targets using real-time
      PCR. RESULTS: Compression of H-PDLFs resulted in a significant increase only in
      MMP-1 mRNA. In contrast, the same compressive force on D-PDLFs produced
      significant increases in the expression of MMPs-1,-7,-9 and -16. Moreover,
      compression of H-PDLFs resulted in down-regulation of IL-6, while IL-6 was
      significantly up-regulated in compressed D-PDLFs. Compression of H-PDLFs slightly
      up-regulated 3 and significantly down-regulated 15 inflammation-related genes,
      while the same treatment strongly up-regulated 21 inflammation-related genes in D
      PDLFs. CONCLUSION: These results suggest a fundamental difference in the
      inflammatory response of healthy versus diseased PDLFs under physiological
      compression. Maintenance of these characteristics in vitro suggests that these
      cells may be at least partly responsible for the persistence of inflammation and
      localized susceptibility in chronic periodontitis.

PMID- 23560812
TI  - Recent progress in satellite cell/myoblast engraftment -- relevance for therapy.
AB  - There is currently no cure for muscular dystrophies, although several promising
      strategies are in basic and clinical research. One such strategy is cell
      transplantation with satellite cells (or their myoblast progeny) to repair
      damaged muscle and provide dystrophin protein with the aim of preventing
      subsequent myofibre degeneration and repopulating the stem cell niche for future
      use. The present review aims to cover recent advances in satellite cell/myoblast
      therapy and to discuss the challenges that remain for it to become a realistic
      therapy. 

PMID- 23560814
TI  - Ret transgenic mouse model of spontaneous skin melanoma: focus on regulatory T
      cells.
AB  - Ret transgenic mouse model of skin malignant melanoma is characterized by the
      overexpression of the human ret transgene in melanin-containing cells. Transgenic
      mice spontaneously develop skin tumors with metastases in lymph nodes, lungs,
      liver, brain, and the bone marrow. Tumor lesions show typical melanoma morphology
      and express melanoma-associated antigens. Although transgenic mice demonstrate an
      accumulation of melanoma antigen-specific memory and effector T cells, their anti
      tumor effects could be blocked by highly immunosuppressive leukocytes enriched in
      the tumor microenvironment and in the periphery. Here, we discuss the role of one
      of the most potent immunosuppressive subset, regulatory T cells, in the melanoma
      progression in this model. 

PMID- 23560815
TI  - Increasing the phenolic compound content of grapes by preharvest application of
      abcisic acid and a combination of methyl jasmonate and benzothiadiazole.
AB  - Benzothiadiazole (BTH) and methyl jasmonate (MeJ) have been described as
      exogenous elicitors of some plant defense compounds, polyphenols among them.
      Given that they activate different arrays of biochemical reactions to induce
      resistance, the objective of this study was to determine whether the joint
      application of BTH and MeJ to grape clusters affects the level of the main
      flavonoid compounds in grapes and in the resulting wines. The results are
      compared with those obtained when abscisic acid (ABA), a plant growth regulator
      involved in several physiological processes, was sprayed in the same vineyard.
      The results obtained indicated that, although the application of ABA increased
      the content of skin anthocyanins and tannins, these positive effects were not
      reflected in the wines made from these grapes. BTH+MeJ-treated grapes also
      presented higher anthocyanin and flavonol contents, and in this case, their wines
      presented better chromatic characteristics that the wine made from control
      grapes. 

PMID- 23560816
TI  - A novel sorting technology allows for highly efficient selection of sperm without
      chromatin damage.
AB  - Sperm chromatin damage has been associated with male infertility, increased risk
      for spontaneous abortion, and poor embryo development. Available methods for
      detecting chromatin damage render the sperm no longer suitable for clinical use.
      Early apoptotic events resulting in chromatin damage are associated with
      increased permeability of the cell membrane to large ions. We propose the use of
      a large fluorescent organic cation, proprietary fluorochrome (PF-1), for
      fluorescence-activated cell sorting (FACS) for negative selection of sperm
      without chromatin damage. Sperm with chromatin damage are PF-1 positive.
      Performance of cell sorting by PF-1 was verified with terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) after FACS on PF-1(+) and PF-1(-)
      subpopulations. Whereas 19.5% of PF-1 positive sperm were TUNEL positive only
      1.5% sperm in the PF-1(-) fraction were TUNEL positive (p < 0.00001). TUNEL
      values below 1.9% were considered background fluorescence. Post-sorting motility
      and vitality were 49.4% (SD: 12.5) and 65.0% (SD: 14.99), respectively.
      Proprietary fluorochrome activated sperm sorting may decrease or most likely
      eliminate all of TUNEL positive sperm without adverse effects on viability,
      providing a new therapeutic avenue for men with a high percentage of TUNEL
      positive sperm. Further research is needed to determine if the reduction in TUNEL
      positive sperm using PF-1 will improve in vitro fertilization (IVF) outcomes.

PMID- 23560817
TI  - Carbon-based nanomaterials: multifunctional materials for biomedical engineering.
AB  - Functional carbon-based nanomaterials (CBNs) have become important due to their
      unique combinations of chemical and physical properties (i.e., thermal and
      electrical conductivity, high mechanical strength, and optical properties), and
      extensive research efforts are being made to utilize these materials for various
      industrial applications, such as high-strength materials and electronics. These
      advantageous properties of CBNs are also actively investigated in several areas
      of biomedical engineering. This Perspective highlights different types of carbon
      based nanomaterials currently used in biomedical applications.

PMID- 23560818
TI  - Microparticles in stored canine RBC concentrates.
AB  - BACKGROUND: Transfusion of RBC concentrates may cause adverse effects in the
      recipient, particularly when stored > 2 weeks. Prestorage removal of WBCs and
      platelets (leukoreduction, LR) improves clinical outcome in the human recipient.
      As blood ages during storage, progressive alterations in the structure and
      function of the cells occur. Changes in cell membranes may lead to formation of
      microparticles (MPs) in stored blood. OBJECTIVES: The aim of the study was to
      quantify MP concentration in supernatants from canine RBC concentrates from 11
      clinically healthy dogs. METHODS: Whole blood units (n = 11) were collected and
      randomized either to be stored without LR (n = 5), or to be subject to prestorage
      LR (n = 6). Whole blood was processed for the generation of RBC concentrates,
      from which aliquots were aseptically collected weekly for 5 weeks. Supernatants
      from the concentrates were evaluated for phosphatidylserine-expressing MPs by
      flow cytometry using staining with Annexin-V-phycoerythrin. RESULTS:
      Microparticle counts were similar between non-LR and LR units on storage days 0
      and 7, but were significantly higher in non-LR units on days 14, 21, 28, and 35.
      MPs increased during the 35-day storage by a mean (SD) of 1.8 (1.4)-fold in LR
      units and 5.5 (3.1)-fold in non-LR units. CONCLUSIONS: There was marked formation
      of phosphatidylserine-expressing MPs during storage beyond 7 days in canine RBC
      concentrates. Prestorage LR attenuated the generation of MPs.

PMID- 23560819
TI  - Zymogen activation of neurotrypsin and neurotrypsin-dependent agrin cleavage on
      the cell surface are enhanced by glycosaminoglycans.
AB  - The serine peptidase neurotrypsin is stored in presynaptic nerve endings and
      secreted in an inactive zymogenic form by synaptic activity. After activation,
      which requires activity of postsynaptic NMDA (N-methyl-D-aspartate) receptors,
      neurotrypsin cleaves the heparan sulfate proteoglycan agrin at active synapses.
      The resulting C-terminal 22-kDa fragment of agrin induces dendritic filopodia,
      which are considered to be precursors of new synapses. In the present study, we
      investigated the role of GAGs (glycosaminoglycans) in the activation of
      neurotrypsin and neurotrypsin-dependent agrin cleavage. We found binding of
      neurotrypsin to the GAG side chains of agrin, which in turn enhanced the
      activation of neurotrypsin by proprotein convertases and resulted in enhanced
      agrin cleavage. A similar enhancement of neurotrypsin binding to agrin,
      neurotrypsin activation and agrin cleavage was induced by the four-amino-acid
      insert at the y splice site of agrin, which is crucial for the formation of a
      heparin-binding site. Non-agrin GAGs also contributed to binding and activation
      of neurotrypsin and, thereby, to agrin cleavage, albeit to a lesser extent.
      Binding of neurotrypsin to cell-surface glycans locally restricts its conversion
      from zymogen into active peptidase. This provides the molecular foundation for
      the local action of neurotrypsin at or in the vicinity of its site of synaptic
      secretion. By its local action at synapses with correlated pre- and post-synaptic
      activity, the neurotrypsin-agrin system fulfils the requirements for a mechanism
      serving experience-dependent modification of activated synapses, which is
      essential for adaptive structural reorganizations of neuronal circuits in the
      developing and/or adult brain.

PMID- 23560820
TI  - Morphology-driven nonwettability of nanostructured BN surfaces.
AB  - Designing geometrical structures is an effective route to tailoring the
      wettability of a surface. BN-based hierarchical nano- and microstructures, in
      particular, vertically aligned and randomly distributed tubes and cones, were
      synthesized and employed as a platform for studying the influence of surface
      morphology on their static and dynamic interactions with water droplets. The
      variation of the contact angle in different hierarchical BN films is attributed
      to the combined effects of surface roughness and partial liquid-solid contact at
      the interface. Moreover, the impact response of water droplets impinging on BN
      arrays with different wetting properties is distinct. In the case of
      superhydrophobic films, the water droplet bounces off the surface several times
      whereas in less hydrophobic films it does not rebound and remains pinned to the
      surface. These results provide a facile route for the selective preparation of
      hierarchical BN nanostructure array films and a better understanding of their
      tunable water-repelling behavior, for which a number of promising applications in
      microelectronics and optics can be envisaged.

PMID- 23560821
TI  - Polymeric microparticles-based formulation for the eradication of cutaneous
      candidiasis: development and characterization.
AB  - Cutaneous candidiasis is a common topical fungal infection which may be more
      prominent in patients associated with AIDS. It is usually treated by conventional
      formulations such as cream, gel, which show various adverse effects on skin along
      with systemic absorption. To overcome these drawbacks, various novel drug
      delivery systems have been explored. Poly(lactic-co-glycolic acid) (PLGA)-based
      microparticulate systems have shown good dermal penetration after topical
      application. Therefore, in the present study clotrimazole-loaded PLGA
      microspheres were prepared for targeted dermal delivery. Microspheres were
      prepared by using a single emulsification (oil-in-water, O/W) evaporation
      technique and characterized for different parameters. Prepared microparticulate
      systems were dispersed in Carbopol 934(r) gel and antifungal activity was carried
      out on experimentally induced cutaneous candidiasis in immunosuppressed guinea
      pigs. Particle size of optimized formulation was 2.9 um along with 74.85%
      entrapment of drug. Skin retention studies revealed that drug accumulation in the
      skin was higher with microspheres gel as compared to marketed gel. Confocal
      microscopy of skin further confirmed penetration of microspheres up to 50 um into
      the dermal region. In-vivo antifungal activity studies demonstrated that
      microsphere gel showed better therapeutic activity, lowest number of cfu/ml was
      recorded, as compared to marketed gel after 96 h of application. Based on the
      results of the study, it can be concluded that PLGA microparticles may be
      promising carriers to deliver clotrimazole intradermally for the treatment of
      invasive fungal infections.

PMID- 23560822
TI  - Nutritional intake according to injury extent in ulcerative colitis patients.
AB  - BACKGROUND: Ulcerative colitis (UC) is often associated with nutritional
      deficiency, which appears to contribute to the progression of UC severity. The
      present study aimed to evaluate nutritional status and dietary intake in UC
      remission patients. METHODS: The present study comprised a cross-sectional study
      in which variables such as extent of disease (distal colitis, left-sided colitis,
      pancolitis), remission period, sex and age were recorded. Extent of disease was
      assessed by the results of a colonoscopy and dietary intake was evaluated by
      using 3-day, 24-h recalls. A Kruskall-Wallis test was used to compare the intake
      of macro- and micronutrients among the three study groups. The analysis was
      complemented by the Mann-Whitney test. A logistic regression analysis was
      performed to identify predictive factors of extent of disease (pancolitis versus
      left-sided colitis versus distal colitis). RESULTS: The median (range) age of the
      59 patients was 49.0 (37.0-63.0) years and 53.3% were female. Twenty-six (44.1%)
      patients had distal colitis, 11 (18.6%) patients had left-sided colitis and 22
      (37.3%) patients had pancolitis. A high probability of an inadequate intake of
      fibre (100%), fat soluble vitamins (>40% for vitamin A and >95% for vitamin E),
      vitamin C (>34%), calcium (>90%) and magnesium (>50%) was identified in the study
      group. Vitamin D intake (odds ratio = 0.60; 95% confidence interval = 0.39-0.94;
      P < 0.05) was significantly associated with increased intestinal damage.
      CONCLUSIONS: A large number of individuals showed an inadequate intake of
      nutrients. In addition, the consumption of vitamin D was significantly associated
      with extent of disease.

PMID- 23560823
TI  - Successful wound healing over exposed metal implants using vacuum-assisted wound
      closure in a dog.
AB  - An eight-month-old Labrador retriever was presented with a grade IIIb open
      shearing injury of the left tarsus. Acute severe surgical site infection
      developed 2 days after pan-tarsal arthrodesis, resulting in wound dehiscence.
      Vacuum-assisted wound therapy was carried out for 12 days to treat an extensive
      full-thickness soft tissue defect with exposure of metal implants. New
      granulation tissue formation covering most of the defect was achieved by day 10
      of this therapy. Epithelialization was achieved by second intention healing with
      open wound management. To the authors' knowledge, this is the first veterinary
      clinical case report documenting complete healing over exposed metal implants
      without any requirement for surgical revision. 

PMID- 23560824
TI  - Hydrazine-mediated reduction of nitro and azide functionalities catalyzed by
      highly active and reusable magnetic iron oxide nanocrystals.
AB  - Iron oxide (Fe3O4) nanocrystals generated in situ from an inexpensive and readily
      available iron source catalyze the reduction of nitroarenes to anilines with
      unparalleled efficiency. The procedure is chemoselective, avoids the use of
      precious metals, and can be applied under mild reflux conditions (65 or 80 
      degrees C) or using sealed vessel microwave heating in an elevated temperature
      regime (150  degrees C). Utilizing microwave conditions, a variety of
      functionalized anilines have been prepared in nearly quantitative yields within 2
      8 min at 150  degrees C, in a procedure also successfully applied to the
      reduction of aliphatic nitro compounds and azides. The iron oxide nanoparticles
      are generated in a colloidal form, resulting in homogeneous solutions suitable
      for continuous flow processing. Selected examples of anilines of industrial
      importance have been prepared in a continuous regime using this protocol.

PMID- 23560825
TI  - Influence of multiple initiatives in Sweden to enhance ARB prescribing efficiency
      following generic losartan; findings and implications for other countries.
AB  - BACKGROUND: Encouraging the prescribing of ACEIs first line vs. angiotensin
      receptor blockers (ARBs) has been a health authority focus with generic ACEIs as
      ACEIs and ARBs have similar effectiveness and there is limited coughing with
      ACEIs. This includes Sweden with its multiple initiatives keeping expenditure on
      renin-angiotensin inhibitor drugs similar between 2001 and 2007 despite
      appreciably increased volumes. Generic losartan became available and was
      reimbursed in March 2010 providing further opportunities for the authorities in
      Sweden to save costs with all ARBs seen as similar in managing hypertension and
      CHF at appropriate doses. AIMS: The main aim of this study was to assess changes
      in the utilisation of losartan vs. other single ARBs after generic losartan
      alongside accompanying demand-side measures. Additional aims were to (i) assess
      changes in the price of generic losartan and single ARB expenditure over time;
      (ii) suggest additional programmes, if needed; and (iii) analyse utilisation of
      ARB FDCs and compare with ACEI FDCs. METHODS: Retrospective observational study
      using an interrupted time series design. RESULTS: Multiple demand-side measures
      introduced among the 21 Counties in Sweden significantly enhanced the utilisation
      of generic losartan, growing from 26% to 27% of total ARBs (DDD basis) before
      generic losartan to 40% by August 2011. Losartan was principally generics (97% by
      August 2011). Expenditure/DDD for generic losartan was 10% of the pre-patent loss
      price in August 2011. This reduced total single ARB expenditure by 26% by the
      study end despite a 16% increase in utilisation. Greater utilisation of ARB FDCs
      than seen with ACEI FDCs. This may be due to similarities in prices between
      single and FDC ARBs. DISCUSSION: Multiple demand-side measures appreciably
      enhanced ARB prescribing efficiency, mirroring other studies. No significant
      increase in losartan utilisation following generics was seen in European
      countries where no specific measures were instigated. Losartan price reduction
      was in line with expectations. CONCLUSION: Multiple and intensive demand-side
      measures are needed to change physician prescribing habits. Authorities cannot
      rely on physicians transferring their activities from one class to another
      without interventions.

PMID- 23560826
TI  - An effective hair removal algorithm for dermoscopy images.
AB  - BACKGROUND/PURPOSE: Dermoscopy is one of the major imaging modalities used in the
      diagnosis of pigmented skin lesions. Due to the difficulty and subjectivity of
      human interpretation, computerized image analysis techniques have become
      important tools in this research area. Hair removal from skin lesion images is
      one of the key problems for the precise segmentation and analysis of the skin
      lesions. In this study, we present a new scheme that automatically detects and
      removes hairs from dermoscopy images. METHODS: The proposed algorithm includes
      two steps: firstly, light and dark hairs and ruler marking are segmented through
      adaptive canny edge detector and refinement by morphological operators. Secondly,
      the hairs are repaired based on multi-resolution coherence transport inpainting.
      RESULTS: The algorithm was applied to 50 dermoscopy images. To estimate the
      accuracy of the proposed hair detection algorithm, quantitative analysis was
      performed using TDR, FPR, and DA metrics. Moreover, to evaluate the performance
      of the proposed hair repaired algorithm, three statistical metrics namely
      entropy, standard deviation, and co-occurrence matrix were used. CONCLUSION: The
      results demonstrate that the proposed algorithm is highly accurate and able to
      detect and repair the hair pixels with few errors. In addition, the segmentation
      veracity of the skin lesion is effectively improved after our proposed hair
      removal algorithm.

PMID- 23560828
TI  - Using reproductive immunology to improve clinical practices.
AB  - The American Society for Reproductive Immunology's Second Clinical Reproductive
      Immunology Symposium: 'Using Reproductive Immunology to Improve Clinical
      Practices' was held on October 27th to 28th 2012, in New Haven, Connecticut. The
      objective of this symposium was to disseminate up-to-date clinical reproductive
      immunology information and how it relates to current clinical practices,
      diagnostics, and therapeutics for women's reproductive and pregnancy-related
      issues, with a view to bridging the distance between clinicians and translational
      researchers. It provided a common platform to physicians and physician scientists
      to facilitate the application of research outcomes into current medical practice.
      This symposium highlighted the current status of health issues during pregnancy
      including preeclampsia, preterm birth, maternal obesity and diabetes,
      autoimmunity and infection. In addition, a session was dedicated toward
      demystifying laboratory techniques of reproductive immunology for clinicians.
      This symposium was attended by approximately 50 delegates along with the 16
      invited speakers and included 17 presentations that addressed key issues in the
      immunology of maternal-fetal well-being. This report will summarize the
      highlights of the meeting.

PMID- 23560827
TI  - The role of transient elastography in the detection of liver disease in patients
      with chronic pancreatitis.
AB  - BACKGROUND & AIMS: Quantification of liver stiffness with transient elastography
      (TE) is validated for staging hepatic fibrosis in chronic hepatitis C infection.
      The current study was aimed to assess the diagnostic performance of liver
      stiffness measurement for the determination of fibrosis stage in patients with
      chronic pancreatitis. METHODS: Thirty consecutive patients with chronic
      pancreatitis and increased liver enzyme were enrolled over a 2.5-year period.
      Eight liver living donor candidates were recruited to serve as internal controls.
      The TE values were compared with non-invasive fibrosis scoring systems including
      aspartate transaminase (AST)/alanine aminotransferase (ALT) ratio, APRI, non
      alcoholic fatty liver disease NAFLD score, FIB-4 index and to liver histology.
      RESULTS: TE was successful in all patients. Stiffness values ranged from 3.1 to
      69 kPa (mean 16.9). Liver stiffness was correlated with fibrosis stage
      (Spearman's correlation 0.73, P < 0.0001). Areas under receiver operator
      characteristics curves for fibrosis F = 4 were 0.92 for TE, 0.87 for FIB-4 index,
      0.81 for APRI, 0.73 for NAFLD score and 0.71 for AST/ALT ratio. Optimal stiffness
      cut-off values for diagnosis fibrosis F = 4 was 10.9 kPa, with 90% sensitivity,
      85% specificity and 86% accuracy. CONCLUSION: Our study provides for the first
      time evidence that liver stiffness in patients with chronic pancreatitis and
      concomitant cholestasis can be measured by TE.

PMID- 23560829
TI  - Premalignant conditions of gastric cancer.
AB  - Premalignant lesions of gastric cancer encompass a variety of conditions such as
      chronic gastritis, intestinal metaplasia and dysplasia, in which elevated risk of
      developing gastric cancer have been documented. Among them, intestinal metaplasia
      is frequently encountered in our daily endoscopic examination, yet its clinical
      significance is often underestimated despite of a number of reports demonstrating
      genetic and epigenetic alterations in the intestinal metaplastic mucosa. In this
      review, I will describe the molecular mechanisms of phenotypic changes from
      gastric mucosa to intestinal metaplasia based on our analysis of mouse model of
      intestinal metaplasia generated by ectopic expression of CDX2 in conjunction with
      the studies with human intestinal metaplasia.

PMID- 23560830
TI  - Evaluation of methane sources in groundwater in northeastern Pennsylvania.
AB  - Testing of 1701 water wells in northeastern Pennsylvania shows that methane is
      ubiquitous in groundwater, with higher concentrations observed in valleys vs.
      upland areas and in association with calcium-sodium-bicarbonate, sodium
      bicarbonate, and sodium-chloride rich waters--indicating that, on a regional
      scale, methane concentrations are best correlated to topographic and
      hydrogeologic features, rather than shale-gas extraction. In addition, our
      assessment of isotopic and molecular analyses of hydrocarbon gases in the Dimock
      Township suggest that gases present in local water wells are most consistent with
      Middle and Upper Devonian gases sampled in the annular spaces of local gas wells,
      as opposed to Marcellus Production gas. Combined, these findings suggest that the
      methane concentrations in Susquehanna County water wells can be explained without
      the migration of Marcellus shale gas through fractures, an observation that has
      important implications for understanding the nature of risks associated with
      shale-gas extraction.

PMID- 23560831
TI  - Cancer therapy: could a novel test predict the amount of drug that reaches its
      target?

PMID- 23560833
TI  - Regorafenib: carving a niche in the crowded therapeutic landscape.
AB  - The oral multikinase inhibitor regorafenib targets both tumor cell proliferation
      and vasculature and is active in heavily pretreated patients with metastatic
      colorectal cancer, for which the US FDA granted its approval in September 2012.
      The benefit for regorafenib was seen in these patients in most prespecified
      subgroups. The drug is also being used in other tumor types where it has shown
      exciting potential especially in gastrointestinal stromal tumors. The drug is
      well tolerated but requires close monitoring during administration. Common side
      effects include asthenia/tiredness, loss of appetite, hand-foot skin syndrome,
      diarrhea, mucositis, weight loss, infections, hypertension and rash. Serious
      adverse events to look out for are liver toxicity, hemorrhage and
      gastrointestinal perforation. Biomarker data should help us to optimize the use
      of these drugs to select which patients are most likely to benefit.

PMID- 23560834
TI  - Management of abdominal malignancies: updates from the International Association
      of Surgeons, Gastroenterologists and Oncologists.
AB  - The 22nd World Congress of the International Association of Surgeons,
      Gastroenterologists and Oncologists was held from 5-8 December 2012 in Bangkok,
      Thailand. Themed 'Challenges and Controversies in the Management of Abdominal
      Diseases: Current Possibility and Future Expectation', the congress featured ten
      main topics including: upper GI tract surgery, lower GI tract surgery, hepatic
      surgery, biliary tract surgery, pancreatic surgery, interventional chemo-immuno
      radiotherapy, laparoscopic endoscopic surgery, multidisciplinary approaches,
      innovation and advanced technology and robotic surgery. Approximately 200 guest
      speakers were invited to share their experiences and expertise, while 600
      abstracts were submitted for oral and poster presentations. In this article, the
      authors highlight and summarize some of the presentations from this conference.

PMID- 23560835
TI  - The first antibody therapy for cancer: a personal experience.
AB  - More than 100 years ago, Paul Ehrlich proposed that antibodies could be used for
      therapeutic purposes. Little progress was achieved until Kohler and Milstein
      developed hybridoma technology in the 1970s. In 1997, rituximab, the first
      antibody for the treatment of cancer, was approved. Its development (laboratory
      and clinical) broke records, provided proof of concept for antibodies as
      anticancer agents and opened the floodgates for research in the area. Rituximab,
      in combination with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone
      chemotherapy, was proven to increase the cure rate for patients with diffuse
      large cell lymphoma. Hopefully, over the next decades, we will find additional
      indications where antibodies in combination with other agents result in making
      patients cancer free, provide long-term survival and cures.

PMID- 23560836
TI  - Anaplastic lymphoma kinase: a glimmer of hope in lung cancer treatment?
AB  - Anaplastic lymphoma kinase (ALK) rearrangements (ALK-Rs) have been identified in
      3-7% of all non-small-cell lung cancers (NSCLCs) and represent an important
      molecular target for NSCLC treatment. The authors discuss the role of ALK-Rs in
      the prediction of clinical-pathological features of NSCLCs and the technical
      problems related to their determination in specimens. The authors also describe
      the preclinical and clinical results derived from the use of ALK inhibitors. ALK
      R is generally detected in patients with specific clinical-pathological features:
      never-smokers, young males, adenocarcinoma histotype and EGF receptor/KRAS wild
      type. The diagnosis of ALK-R remains a challenge, implicating the need of a
      careful filtering of patients. NSCLC patients harboring ALK-R have shown
      sensitivity to ALK inhibitors even if their activity is limited at the time by
      the occurrence of mechanisms of resistance. The authors summarize the strategies
      that in the future could overcome these mechanisms of escape.

PMID- 23560837
TI  - Zoledronic acid in lung cancer with bone metastases: a review.
AB  - Lung cancer remains the leading cause of cancer mortality worldwide and bone
      metastases develop in approximately 30-40% of cases. Bisphosphonates are a key
      therapy for bone metastases; zoledronic acid is the only bisphosphonate with
      efficacy in preventing, reducing the incidence and delaying the onset of skeletal
      related events controlling bone pain. Several bone metabolism markers indicate
      bone resorption activity, linking with prognosis and efficacy of zoledronic acid.
      Zoledronic acid has a well-established tolerability profile and can be
      administered safely as long-term therapy, although preventive measures are needed
      to avoid some severe side effects (nephrotoxicity and osteonecrosis of the jaw)
      found in a small number of patients receiving long-term therapy. Currently, lung
      cancer patients with bone metastases are candidates to receive zoledronic acid in
      clinical practice with demonstrated benefits and safety preserving quality of
      life. Additional roles in anticancer activity deserve attention and are under
      investigation.

PMID- 23560838
TI  - Current and emerging surveillance strategies to expand the window of opportunity
      for curative treatment after surgery in colorectal cancer.
AB  - Colorectal cancer is the third most common cancer globally. At diagnosis, more
      than 70% of patients have nonmetastatic disease. Cure rates for early-stage
      colorectal cancer have improved with primary screening, improvements in surgical
      techniques and advances in adjuvant chemotherapy. Despite optimal primary
      treatment, 30-50% of these patients will still relapse. While death will result
      from widespread metastatic disease, patients with small volume oligometastatic
      disease are still considered curable with aggressive multimodality therapy.
      Hence, early detection of relapsed cancer when it is still amenable to resection
      expands the window of opportunity for cure. Here, the authors review the
      modalities currently employed in clinical practice and the evidence supporting
      intensive surveillance strategies. The authors also discuss ongoing clinical
      trials examining specific surveillance programs and emerging modalities that may
      be deployed in the future for early detection of metastatic disease.

PMID- 23560839
TI  - Neuroendocrine neoplasms of the GI tract: the role of cytotoxic chemotherapy.
AB  - Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of neoplasms
      derived from peptide- and amine-secreting cells of the neuroendocrine system.
      NENs commonly arise in the GI tract but can arise in most organs of the body.
      NENs in different organs share many common pathologic features. Although the
      incidence of NENs is not high, the prevalence is not low because many patients
      may live relatively long periods without major symptoms from the disease. While
      many of these tumors lead an indolent clinical course, they constitute a
      therapeutic challenge when they progress, metastasize and become symptomatic.
      Treatment requires a multidisciplinary approach including cytotoxic chemotherapy.
      Almost all clinical trials investigating cytotoxic chemotherapy in NENs are small
      single-arm studies and guidelines are derived from expert opinion and from
      extrapolating results from small cell lung cancer studies. This article briefly
      reviews NENs before focusing on reviewing data on the role of cytotoxic
      chemotherapy studies in NENs.

PMID- 23560840
TI  - Colorectal cancer stem cells and their implications for novel anticancer therapy.
AB  - Anticancer therapy relies on targeting highly proliferative cells. Commonly used
      chemotherapy does not selectively target individual cancer cells. The
      identification of distinct cancer stem cells that have the unique ability to
      engraft tumors and maintain cancer self-renewal may prove vital in the
      development of novel and selective anticancer therapy. Therefore, the discovery
      of colorectal cancer stem cell markers has attracted much attention. However, it
      is still controversial whether current markers for cancer cell subpopulations are
      selectively labeling cancer stem cells, whether these markers contribute to
      cancer stem cell function and how many cells within tumors maintain this
      stemness. For this reason, novel anticancer drug approaches need to be
      considered, that target selective cell death pathways, the tissue
      microenvironment and, additionally, multiple specific cancer (stem) cell markers.
      This triple approach of anticancer therapy may contribute to novel
      chemotherapeutic strategies and improve the understanding of human intestinal
      tumorigenesis; in particular, the distinct contribution of human cancer stem
      cells.

PMID- 23560841
TI  - Treatment of hepatocellular carcinoma: present and future.
AB  - Hepatocellular carcinoma is a major health problem. It is the sixth most common
      cancer worldwide and the third most common cause of cancer-related death. Despite
      the availability of several treatment opportunities, diagnosis is still made in
      an advanced phase, limiting application of most therapeutic choices that
      currently are based on the Barcelona Clinic Cancer Liver Classification and
      include surgical resection, orthotopic liver transplantation and ablative methods
      for very early and early disease, arterial chemoembolization for intermediate
      stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma.
      Thanks to novel advancements in knowledge of molecular pathogenesis of this
      tumor, many new systemic agents and locoregional treatments are in different
      stages of clinical development and they represent an important promise of further
      improvements in patients' survival.

PMID- 23560842
TI  - Emerging role of stereotactic body radiotherapy in the treatment of pancreatic
      cancer.
AB  - The management of pancreatic cancer continues to be challenging. Despite
      surgical, genetic and molecular advances, its overall prognosis remains poor.
      Surgical resection is the only modality that offers a chance for a cure, with an
      overall survival rate of 10-20% at 5 years. However, only 20% of the patients are
      surgical candidates because of locally advanced disease or systemic stage at
      presentation. Conventional radiotherapy, with or without chemotherapy, has been
      used to treat patients with advanced-stage pancreatic cancer, an approach with
      high rates of local recurrence. Stereotactic body radiation therapy, also known
      as stereotactic ablative radiotherapy has emerged as a treatment modality that
      allows the precise delivery of a large ablative radiation dose to a tumor volume
      while sparing surrounding organs and tissues. Phase I and II studies have shown
      good rates of local control of the disease but rates of distant metastasis remain
      significant. Strategies to combine novel systemic therapy and stereotactic body
      radiation therapy are to be explored.

PMID- 23560843
TI  - Quality of reporting and its correlates among randomized controlled trials on
      acupuncture for cancer pain: application of the CONSORT 2010 Statement and
      STRICTA.
AB  - This study aims to analyze the quality of reporting and its correlates in
      randomized controlled trials (RCTs) on acupuncture for cancer pain. Quality of
      reporting for included papers was assessed against a subset of criteria adapted
      from the CONSORT 2010 statement and STRICTA. An overall quality score (OQS) and a
      combined key methodologic index score (MIS) was calculated for each trial.
      Factors associated with OQS and MIS were then identified. A total of 32 RCTs were
      included in the full text. The median OQS based on the CONSORT Statement and
      STRICTA was 4.0 and 0, respectively. The significant predictors for CONSORT OQS
      were year of publication and nationality of authors, for STRICTA it was
      nationality of authors and for MIS it was publication language. The quality of
      reporting in RCTs on acupuncture for cancer pain was poor. This indicates that
      RCTs on acupuncture for cancer pain need substantial improvement.

PMID- 23560844
TI  - Metal-dependent protein phosphatase 1A functions as an extracellular signal
      regulated kinase phosphatase.
AB  - Protein phosphorylation is an important post-translational modification that
      regulates almost every aspect of signal transduction in cells. Activation of the
      mitogen-activated protein kinase (MAPK) family kinase extracellular signal
      regulated kinase (ERK) is a point of convergence for many cellular activities in
      response to external stimulation. With stimuli, ERK activity is significantly
      increased by the phosphorylation of Thr202 and Tyr204 at its activation loop.
      Downregulation of ERK phosphorylation at these two sites by several phosphatases,
      such as protein phosphatase 2A, HePTP and MAPK phosphatase 3, is essential for
      maintaining appropriate ERK function in different cellular processes. However, it
      is unknown whether metal-dependent protein phosphatase (PPM) family phosphatases
      directly dephosphorylate ERK. In this study, we found that PPM1A negatively
      regulated ERK by directly dephosphorylating its pThr202 position early in EGF
      stimulation. Additional kinetic studies revealed that key residues participated
      in phospho-ERK recognition by PPM1A. Importantly, PPM1A preferred the phospho-ERK
      peptide sequence over a panel of other phosphopeptides through the interactions
      of basic residues in the active site of PPM1A with the pThr-Glu-pTyr motif of
      ERK. Whereas Lys165 and Arg33 were required for efficient catalysis or
      phosphosubstrate binding of PPM1A, Gln185 and Arg186 were determinants of PPM1A
      substrate specificity. The interaction between Arg186 of PPM1A and Glu203 and
      pTyr204 of phospho-ERK was identified as a hot-spot for phospho-ERK-PPM1A
      interaction.

PMID- 23560845
TI  - M2 macrophage polarisation is associated with alveolar formation during postnatal
      lung development.
AB  - BACKGROUND: Macrophages are traditionally associated with inflammation and host
      defence, however a greater understanding of macrophage heterogeneity is revealing
      their essential roles in non-immune functions such as development, homeostasis
      and regeneration. In organs including the brain, kidney, mammary gland and
      pancreas, macrophages reside in large numbers and provide essential regulatory
      functions that shape organ development and maturation. However, the role of
      macrophages in lung development and the potential implications of macrophage
      modulation in the promotion of lung maturation have not yet been ascertained.
      METHODS: Embryonic day (E)12.5 mouse lungs were cultured as explants and
      macrophages associated with branching morphogenesis were visualised by wholemount
      immunofluorescence microscopy. Postnatal lung development and the correlation
      with macrophage number and phenotype were examined using Colony-stimulating
      factor-1 receptor-enhanced green fluorescent protein (Csf1r-EGFP) reporter mice.
      Structural histological examination was complemented with whole-body
      plethysmography assessment of postnatal lung functional maturation over time.Flow
      cytometry, real-time (q)PCR and immunofluorescence microscopy were performed to
      characterise macrophage number, phenotype and localisation in the lung during
      postnatal development. To assess the impact of developmental macrophage
      modulation, CSF-1 was administered to neonatal mice at postnatal day (P)1, 2 and
      3, and lung macrophage number and phenotype were assessed at P5. EGFP transgene
      expression and in situ hybridisation was performed to assess CSF-1R location in
      the developing lung. RESULTS: Macrophages in embryonic lungs were abundant and
      densely located within branch points during branching morphogenesis. During
      postnatal development, structural and functional maturation of the lung was
      associated with an increase in lung macrophage number. In particular, the period
      of alveolarisation from P14-21 was associated with increased number of Csf1r
      EGFP+ macrophages and upregulated expression of Arginase 1 (Arg1), Mannose
      receptor 1 (Mrc1) and Chemokine C-C motif ligand 17 (Ccl17), indicative of an M2
      or tissue remodelling macrophage phenotype. Administration of CSF-1 to neonatal
      mice increased trophic macrophages during development and was associated with
      increased expression of the M2-associated gene Found in inflammatory zone (Fizz)1
      and the growth regulator Insulin-like growth factor (Igf)1. The effects of CSF-1
      were identified as macrophage-mediated, as the CSF-1R was found to be exclusively
      expressed on interstitial myeloid cells. CONCLUSIONS: This study identifies the
      presence of CSF-1R+ M2-polarised macrophages localising to sites of branching
      morphogenesis and increasing in number during the alveolarisation stage of normal
      lung development. Improved understanding of the role of macrophages in lung
      developmental regulation has clinical relevance for addressing neonatal
      inflammatory perturbation of development and highlights macrophage modulation as
      a potential intervention to promote lung development.

PMID- 23560846
TI  - New stilbenoids isolated from fungus-challenged black skin peanut seeds and their
      adipogenesis inhibitory activity in 3T3-L1 cells.
AB  - One new stilbene derivative (3,5,3'-trihydroxy-4'-methoxy-5'-isopentenylstilbene,
      MIP) and two new stilbene dimers (arahypin-11 and arahypin-12) together with
      three known stilbenoids (arachidin-1, arachidin-3, and SB-1) were isolated from
      black skin peanut seeds challenged by the fungal strain Rhizopus oligoporus . The
      structures of the three new compounds were elucidated by analysis of HRESIMS, UV,
      1D and 2D NMR spectra. The antiadipogenic and cytotoxic effects of the isolated
      compounds were investigated using 3T3-L1 cells at a concentration range of 1-10
      MUM. Among the compounds tested, arachidin-1 inhibited the 3T3-L1 adipocyte
      differentiation dose-dependently, whereas arahypin-11 and arahypin-12 exhibited
      significant cytotoxicity in 3T3-L1 preadipocytes. 

PMID- 23560847
TI  - Unspecific increase of tumor markers in a girl with nephrotic syndrome and
      ovarian teratoma.
AB  - Coexistence of nephrotic syndrome and neoplasm is rarely observed in children. We
      report the diagnostic and therapeutic problems of a 16-year-old female with
      nephrotic syndrome, ovarian tumor, and increased levels of tumor markers. She was
      suspected to have paraneoplastic nephrotic syndrome. After ovarian tumor
      resection, the nephrotic syndrome remission was not observed, while increased
      tumor marker levels were noted. The patient's final diagnosis was nephrotic
      syndrome in the course of primary mesangial proliferative glomerulonephritis. In
      conclusion, nephrotic syndrome in a patient with neoplasia might occur in the
      course of the primary and nonparaneoplastic glomerulopathy. Elevated serum tumor
      markers in patients with nephrotic syndrome might be nonspecific because of the
      stimulation of their production by peritoneal mesothelium, due to transudation to
      body cavities, that is, ascites.

PMID- 23560848
TI  - Cross-cultural adaptation and validation of the Physical Therapy Outpatient
      Satisfaction Survey in an Italian musculoskeletal population.
AB  - BACKGROUND: Although patient satisfaction is a relevant outcome measure for
      health care providers, few satisfaction questionnaires have been generally
      available to physical therapists or have been validated in an Italian population
      for use in the outpatient setting. The aim of this study was to translate,
      culturally adapt, and validate the Italian version of the Physical Therapy
      Outpatient Satisfaction Survey (PTOPS). METHODS: The Italian version of the PTOPS
      (PTOPS-I) was developed through forward-backward translation, review, and field
      testing a pre-final version. The reliability of the final questionnaire was
      measured by internal consistency and test-retest stability at 7 days. Factor
      analysis was also used to explore construct validity. Concurrent validity was
      measured by comparing PTOPS-I with a 5-point Likert-type scale measure assessing
      the Global Perceived Effect (GPE) of the treatment and with a Visual Analogue
      Scale (VAS). RESULTS: 354 outpatients completed the PTOPS-I, and 56 took the re
      test. The internal consistency (Cronbach's alpha) of the original domains
      (Enhancers, Detractors, Location, and Cost) was 0.758 for Enhancers, 0.847 for
      Detractors, 0.885 for Location, and 0.706 for Cost. The test-retest stability
      (Intra-class Correlation Coefficients) was 0.769 for Enhancers, 0.893 for
      Detractors, 0.862 for Location, and 0.862 for Cost. The factor analysis of the
      Italian version revealed a structure into four domains, named Depersonalization,
      Inaccessibility, Ambience, and Cost. Concurrent validity with GPE was
      significantly demonstrated for all domains except Inaccessibility. Irrelevant or
      non-significant correlations were observed with VAS. CONCLUSION: The PTOPS-I
      showed good psychometric properties. Its use can be suggested for Italian
      speaking outpatients who receive physical therapy.

PMID- 23560849
TI  - Kinetic modeling of hydrogen conversion at [Fe] hydrogenase active-site models.
AB  - By means of density functional theory, we investigate the catalytic cycle of
      active-site model complexes of [Fe] hydrogenase and study how ligand
      substitutions in the first coordination sphere of the reactive Fe center affect
      the free-energy surface of the whole reaction pathway. Interestingly, dispersion
      interactions between the active site and the hydride acceptor MPT render the
      hydride transfer step less endergonic and lower its barrier. Substitution of CO
      by CN(-), which resembles [FeFe] hydrogenase-like coordination, inverts the
      elementary steps H(-) transfer and H2 cleavage. A simplified kinetic model
      reveals the specifics of the interplay between active-site composition and
      catalysis. Apparently, the catalytic efficiency of [Fe] hydrogenase can be
      attributed to a flat energy profile throughout the catalytic cycle. Intermediates
      that are too stable, as they occur, e.g., when one CO ligand is substituted by
      CN(-), significantly slow down the turnover rate of the enzyme. The catalytic
      activity of the wild-type form of the active-site model could, however, be
      enhanced by a PH3 ligand substitution of the CO ligand.

PMID- 23560850
TI  - Nonionic polymer cross-linked chitosan hydrogel: preparation and bioevaluation.
AB  - A straightforward method to prepare nonionic polymer (polyacrylamide, PAM) cross
      linked chitosan hydrogel has been developed. The chitosan-polyacrylamide (CS-PAM)
      hydrogel could be quickly obtained by simply mixing of chitosan and
      polyacrylamide solutions under very benign condition (room temperature, <30 s).
      The cytotoxicity and hemocompatibility of the CS-PAM hydrogel were subsequently
      investigated. Cells retained normal morphology even when the concentration of CS
      PAM hydrogel in culture system was as high as 640 MUg mL(-1), indicating the CS
      PAM hydrogel has minimal cytotoxicity to A549 and HeLa cells. Meanwhile, no
      hemolysis was observed after incubating the CS-PAM hydrogel with red blood cells
      for 6 h, further suggesting excellent biocompatibility of the hydrogel. Scanning
      electron microscopy images illustrated that the CS-PAM hydrogel can absorb red
      blood cells through the interaction between the protonated amine groups on
      chitosan and the negative charged residues on red blood cell membranes. Given its
      low cost, simple preparation, and excellent biocompatibility, this CS-PAM
      hydrogel might be a potential biomaterial for future healthcare and biomedical
      applications. 

PMID- 23560851
TI  - [none].

PMID- 23560852
TI  - The devil in the detail of secretions.

PMID- 23560853
TI  - Parent-adolescent conflict, treatment adherence and glycemic control in Type 1
      diabetes: the importance of adolescent externalising symptoms.
AB  - Parent-adolescent conflict has been demonstrated to relate to treatment adherence
      and glycemic control in adolescents with Type 1 diabetes. The present
      longitudinal study investigated how these variables were interrelated over time,
      and examined whether externalising and internalising symptoms function as
      mediating variables. A total of 109 adolescents with diabetes participated at
      four annual time points and completed measures on conflict with parents,
      internalising and externalising symptoms. Information on treatment non-adherence
      and glycemic control was obtained from treating physicians. Cross-lagged analyses
      from a structural equation modelling approach indicated that father-adolescent
      but not mother-adolescent conflict positively influenced treatment non-adherence
      over time, which, in turn, was associated with higher glycosylated haemoglobin
      values. Further, externalising but not internalising symptoms were found to
      mediate the pathway from father-adolescent conflict to treatment adherence over
      time. Finally, mother-adolescent conflict was found to relate indirectly to
      treatment non-adherence through its relationship with externalising symptoms.
      Hence, the present longitudinal study provides evidence that externalising
      symptoms represent an important mechanism through which earlier experiences of
      parent-adolescent conflict may influence later treatment non-adherence and poorer
      glycemic control. Implications and suggestions for future research are outlined. 

PMID- 23560855
TI  - Ethical approval, laws and publication of caring science in the Nordic countries.

PMID- 23560854
TI  - Ube2W conjugates ubiquitin to alpha-amino groups of protein N-termini.
AB  - The covalent attachment of the protein ubiquitin to intracellular proteins by a
      process known as ubiquitylation regulates almost all major cellular systems,
      predominantly by regulating protein turnover. Ubiquitylation requires the co
      ordinated action of three enzymes termed E1, E2 and E3, and typically results in
      the formation of an isopeptide bond between the C-terminal carboxy group of
      ubiquitin and the epsilon-amino group of a target lysine residue. However,
      ubiquitin is also known to conjugate to the thiol of cysteine residue side chains
      and the alpha-amino group of protein N-termini, although the enzymes responsible
      for discrimination between different chemical groups have not been defined. In
      the present study, we show that Ube2W (Ubc16) is an E2 ubiquitin-conjugating
      enzyme with specific protein N-terminal mono-ubiquitylation activity. Ube2W
      conjugates ubiquitin not only to its own N-terminus, but also to that of the
      small ubiquitin-like modifier SUMO (small ubiquitin-related modifier) in a manner
      dependent on the SUMO-targeted ubiquitin ligase RNF4 (RING finger protein 4).
      Furthermore, N-terminal mono-ubiquitylation of SUMO-2 primes it for poly
      ubiquitylation by the Ubc13-UEV1 (ubiquitin-conjugating enzyme E2 variant 1)
      heterodimer, showing that N-terminal ubiquitylation regulates protein fate. The
      description in the present study is the first of an E2-conjugating enzyme with N
      terminal ubiquitylation activity, and highlights the importance of E2 enzymes in
      the ultimate outcome of E3-mediated ubiquitylation.

PMID- 23560856
TI  - Dual substrate specificity of Bacillus subtilis PBP4a.
AB  - Bacterial dd-peptidases are the targets of the beta-lactam antibiotics. The sharp
      increase in bacterial resistance toward these antibiotics in recent years has
      stimulated the search for non-beta-lactam alternatives. The substrates of dd
      peptidases are elements of peptidoglycan from bacterial cell walls. Attempts to
      base dd-peptidase inhibitor design on peptidoglycan structure, however, have not
      been particularly successful to date because the specific substrates for most of
      these enzymes are unknown. It is known, however, that the preferred substrates of
      low-molecular mass (LMM) class B and C dd-peptidases contain the free N-terminus
      of the relevant peptidoglycan. Two very similar LMMC enzymes, for example, the
      Actinomadura R39 dd-peptidase and Bacillus subtilis PBP4a, recognize a d-alpha
      aminopimelyl terminus. The peptidoglycan of B. subtilis in the vegetative stage,
      however, has the N-terminal d-alpha-aminopimelyl carboxylic acid amidated. The
      question is, therefore, whether the dd-peptidases of B. subtilis are separately
      specific to carboxylate or carboxamide or have dual specificity. This paper
      describes an investigation of this issue with B. subtilis PBP4a. This enzyme was
      indeed found to have a dual specificity for peptide substrates, both in the acyl
      donor and in the acyl acceptor sites. In contrast, the R39 dd-peptidase, from an
      organism in which the peptidoglycan is not amidated, has a strong preference for
      a terminal carboxylate. It was also found that acyl acceptors, reacting with acyl
      enzyme intermediates, were preferentially d-amino acid amides for PBP4a and the
      corresponding amino acids for the R39 dd-peptidase. Examination of the relevant
      crystal structures, aided by molecular modeling, suggested that the expansion of
      specificity in PBP4a accompanies a change of Arg351 in the R39 enzyme and most
      LMMC dd-peptidases to histidine in PBP4a and its orthologs in other Bacillus sp.
      This histidine, in neutral form at pH 7, appeared to be able to favorably
      interact with both carboxylate and carboxamide termini of substrates, in
      agreement with the kinetic data. It may still be possible, in specific cases, to
      combat bacteria with new antibiotics based on particular elements of their
      peptidoglycan structure.

PMID- 23560857
TI  - Chlorine dioxide inactivation of enterovirus 71 in water and its impact on
      genomic targets.
AB  - To control the waterborne transmission of enterovirus 71(EV71), which is
      associated with hand foot and mouth disease (HFMD), it is essential to know the
      inactivation effectiveness of disinfectants on EV71 in water. In this article, we
      present a comparative analysis of the effects on EV71 following exposure to
      chlorine dioxide (ClO2) under different doses, pH, and temperature conditions. We
      show that the EV71 exhibited strong resistance to ClO2 (more than the MS2
      standard) and that Ct value ranges required for a 4-log reduction of EV71 in
      buffered, disinfectant demand-free water at pH 7.2 and 20  degrees C by ClO2 were
      4.24-6.62 mg/L.min according to the efficiency factor Hom model. ClO2
      inactivation of the virus was temperature- and pH-dependent. The virucidal
      efficiency was higher at pH 8.2 than at pH 5.6 and pH 7.2 and higher at 36 
      degrees C than at 4 and 20  degrees C. In addition, we also observed the impact
      of ClO2 on the entire viral genome using RT-PCR, which indicated that the 5'
      noncoding region (5'-NCR) within the EV71 genome, specifically the 1-118 nt
      region, was the most easily damaged by ClO2 and correlated with viral
      infectivity. Our study has not only provided guidelines for EV71 disinfection
      strategies of waste and drinking water, but also confirmed the importance of the
      5'-NCR for EV71 infectivity and may demonstrate a general inactivation by ClO2 of
      enteric virus by damaging the 5'-NCR. Furthermore, 5'-NCR can be used as a target
      region for PCR to investigate infectious virus contamination in environmental
      water and evaluate the inactivation effects of ClO2.

PMID- 23560858
TI  - A dual-modality photoswitchable supramolecular polymer.
AB  - Covalent or noncovalent linked polymers with stimuli-responsive properties have
      been well researched as a kind of advanced functional materials. However, little
      effort has been devoted to establishing a bridge for switching between covalent
      polymers and noncovalent polymers. Actually, such unitive system is promising
      because it can combine their chemical advantages of two types of polymers in a
      single and tunable platform. Herein, by taking advantage of reversible
      photodimerization of coumarins and host-guest assemblies with gamma-cyclodextrin
      (gamma-CD), we demonstrate a simple and effective way to construct a dual
      modality supramolecular polymer, which can be switched between a noncovalent
      polymer and its corresponding covalent polymer in response to light stimuli.
      Moreover, this unique switchable polymer can also be employed to construct a dual
      stimuli responsive supramolecular hydrogel with the surfactant cetyl
      trimethylammonium bromide (CTAB). This methodology establishes a bridge between
      the two "polymer mansions" and is promising to open a new class of
      photoswitchable materials.

PMID- 23560859
TI  - Left ventricular geometrical differences in dogs with various stages of
      myxomatous mitral valve disease.
AB  - OBJECTIVES: To evaluate left ventricular geometry in dogs with various stages of
      myxomatous mitral valve disease. METHODS: Ninety-seven dogs with myxomatous
      mitral valve disease classified by the International Small Animal Cardiac Health
      Council system and 20 weight- and age-matched healthy dogs. Left ventricular long
      axis to short-axis ratio, sphericity index in end-diastole and end-systole, left
      ventricular wall thickness to internal dimension ratio and relative wall
      thickness were assessed. RESULTS: The diastolic sphericity index was lower in
      classes Ib, II and III than in healthy dogs (P=0.003, P<0.001 and P<0.001) and
      was also lower in class III than in classes Ia, Ib and class II dogs (P<0.001,
      P<0.001 and P=0.002). The relative wall thickness was lower in classes II and III
      than in class Ia (P=0.003 and P<0.001), class Ib (P=0.004 and P<0.001), and
      healthy dogs (P<0.001 and P<0.001) and was also lower in class III than in class
      II (P=0.005). CLINICAL SIGNIFICANCE: Sphericity index and relative wall thickness
      are simple methods for assessing left ventricular geometry using two-dimensional
      echocardiography that may be useful in myxomatous mitral valve disease dogs as
      part of risk stratification.

PMID- 23560860
TI  - Associations of depression, anxiety and antidepressants with histological
      severity of nonalcoholic fatty liver disease.
AB  - BACKGROUND: Depression and anxiety are common in patients with nonalcoholic fatty
      liver disease (NAFLD). However, their associations with histological severity of
      NAFLD are unknown. AIM: This study examined the association(s) of depression,
      anxiety and antidepressant pharmacotherapy with severity of histological features
      in patients with NAFLD. METHODS: We analysed 567 patients with biopsy-proven
      NAFLD enrolled in the Duke NAFLD Clinical Database. Depressive and anxiety
      symptoms were assessed using the Hospital Anxiety & Depression Scale (HADS). The
      associations of depression and anxiety with severity of histological features of
      NAFLD were analysed using multiple logistic (or ordinal logistic) regression
      models with and without adjusting for confounding factors. RESULT: Subclinical
      and clinical depression was noted in 53% and 14% of patients respectively.
      Subclinical and clinical anxiety was noted in 45% and 25% of patients
      respectively. After adjusting for confounders, depression was significantly
      associated with more severe hepatocyte ballooning in a dose-dependent manner
      (likelihood ratio test, P = 0.0201); adjusted cumulative odds ratio (COR) of
      subclinical and clinical depression for having a higher grade of hepatocyte
      ballooning were 2.1 [95% CI, 1.0, 4.4] and 3.6 [95% CI, 1.4, 8.8]. CONCLUSIONS:
      In patients with NAFLD, depression was associated with more severe hepatocyte
      ballooning. Further investigation exploring pathobiological mechanisms underlying
      the observed associations and potential effects of antidepressant pharmacotherapy
      on NAFLD liver histology is warranted.

PMID- 23560861
TI  - Leukopenia in familial Mediterranean fever: case series and literature review
      with special emphasis on pathogenesis.
AB  - Leukopenia is a blood disease in which the number of circulating white blood
      cells diminishes. All underlying causes of leukopenia are not yet known. The
      subjects of this study are 15 leukopenic patients who were assessed by a systemic
      workup, including physical examination, blood tests, and molecular analysis. A
      common and unusual cause was revealed in all patients. This cause was a disorder
      with a laboratory characteristic of leukocytosis, namely familial Mediterranean
      fever (FMF). It was discussed that leukopenia arising in the context of FMF is
      mainly due to autophagy and apoptosis processes. These two pathophysiological
      characteristics of FMF were thought to explain the particular (episodic and self
      limited) leukopenia in this disorder. Based on the results of this study in
      conjunction with the currently existing literature data, we suggest that FMF
      causes leukopenia. Leukopenic cases should be investigated for FMF, particularly
      if the leukopenia is episodic in nature. Early recognition of FMF would help to
      skip unnecessary invasive procedures and to prevent the development of
      amyloidosis, the devastating complication of FMF. 

PMID- 23560862
TI  - Dense-type crypt opening seen on magnifying endoscopy with narrow-band imaging is
      a feature of gastric adenoma.
AB  - BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) can visualize
      crypt openings (CO) as slit-like structures in gastric epithelial neoplasia.
      Visualization of numerous CO is characteristic of low-grade adenoma (LGA). The
      aim of the present study was to investigate whether visualization of CO by ME-NBI
      is useful for discriminating between LGA and early gastric cancer (EGC). PATIENTS
      AND METHODS: Fifty-one superficial elevated-type gastric neoplasias (10 LGA and
      41 EGC) were retrospectively evaluated. The presence of CO and the number of CO
      were evaluated in endoscopic photos obtained at high-power endoscopic
      magnification by ME-NBI. The optimal cut-off value for the number of CO
      visualized to discriminate between LGA and EGC was determined by receiver
      operating characteristic curve analysis. RESULTS: The mean number of CO
      visualized was significantly larger in the LGA group than in the EGC group (31.2,
      95% confidence interval [CI] 16.3-46.1 vs 6.3, 95% CI 3.6-9.0; P < 0.001). When
      the cut-off for the number of CO visualized was set at 20, the sensitivity,
      specificity, and accuracy of dense-type CO for discriminating between LGA and EGC
      were 90.0%, 87.8%, and 88.2%, respectively. CONCLUSION: Determining the number of
      CO visualized in superficial elevated-type gastric neoplasias by ME-NBI appears
      to be a useful method for discriminating between LGA and EGC.

PMID- 23560863
TI  - Case treated with triple therapy of lamivudine, interferon-beta and prednisolone
      for acute exacerbation of chronic hepatitis B during pregnancy.
AB  - We herein report a case of a pregnant Chinese woman who suffered an acute
      exacerbation of hepatitis B. The patient's liver enzymes became elevated toward
      the end of the first trimester. She was treated with lamivudine, interferon (IFN)
      beta and steroids early in the second trimester. After this treatment regimen was
      initiated, aminotransferase levels rapidly normalized within 4 weeks. IFN-beta
      and steroids were administrated for 2 weeks in the second trimester, while the
      administration of lamivudine continued until delivery. The spontaneous delivery
      of a female baby weighing 2984 g occurred at 37 weeks of gestation. A neonatal
      examination revealed no congenital anomalies, and fetal growth was found to be
      within normal reference ranges. The infant received simultaneous active and
      passive hepatitis B virus immunization within 12 h of delivery and completed the
      hepatitis B vaccine schedule at 2, 3 and 5 months of age. The infant was
      successfully prevented from contracting hepatitis B virus. This case suggests
      that combination therapy with lamivudine, IFN-beta and steroids may be safely
      used during the second trimester to treat acute exacerbations of hepatitis B.

PMID- 23560864
TI  - Percutaneous transportal outflow-vessel-occluded sclerotherapy for gastric
      varices unmanageable by balloon-occluded retrograde transvenous obliteration.
AB  - In this report we introduce percutaneous transportal outflow-vessel-occluded
      sclerotherapy (PTOS) for gastric varices unmanageable by balloon-occluded
      retrograde transvenous obliteration (BRTO) in two cases and evaluate its safety
      and efficacy. The PTOS is a technique which could obstruct gastric varices
      subsequent to the occlusion of the outflow route, being based on the rationale of
      BRTO. In the PTOS procedure, coil embolization of the outflow vessel is first
      conducted through a microcatheter advanced beyond the gastric varices via the
      percutaneous transhepatic approach; sclerosing agent (5% ethanolamine oleate) is
      then injected into the gastric varices after confirmation of static blood flow in
      the varices. Two patients underwent initial BRTO that eventually failed because
      of the presence of numerous fine and abruptly angled outflow vessels (case 1),
      and the presence of a tortuous and elongated outflow vessel accompanied by
      numerous small collateral outflows that could not be occluded (case 2). Cases 1
      and 2 received PTOS using 5% ethanolamine oleate (15 mL and 10 mL, respectively).
      Portal venous pressure following PTOS showed an increase from 29 to 34 mmHg in
      case 1 and remained at 24 mmHg in case 2. No major complication was encountered
      in either patient. One-year follow-up gastroendoscopy showed no recurrence of
      gastric varices in either patient. Although PTOS is slightly more invasive than
      BRTO, PTOS can be used as an alternative catheter treatment procedure for gastric
      varices that are unmanageable by BRTO.

PMID- 23560865
TI  - Percutaneous transhepatic sclerotherapy for recurrent bleeding ileal varices
      diagnosed by capsule endoscopy and computed tomography during percutaneous
      transhepatic venography.
AB  - We report a case of acute uncontrolled gastrointestinal bleeding in a patient
      with liver cirrhosis. A 64-year-old man was admitted to our hospital for further
      investigation of blood in stools. Preliminary examination by computed tomography
      (CT) as well as upper and lower endoscopy could not detect the bleeding source.
      Exploratory laparotomy was considered difficult due to potential easy bleeding
      and adhesions caused by past abdominal surgery. The hemoglobin level was
      normalized by blood transfusion. Capsule endoscopy (CE) identified ileal varices.
      The top of these ileal varices was red, prompting their identification as the
      source of bleeding. Percutaneous transhepatic venography (PTV) confirmed the
      presence of many varices in the branch of the superior mesenteric vein, although
      the bleeding source could not be identified. CT during PTV identified varices
      protruding into the ileal lumen, which were managed subsequently by percutaneous
      transhepatic sclerotherapy (PTS). The procedure stopped the bleeding completely.
      CE proved less invasive and effective in detecting obscure gastrointestinal
      bleeding. CT during PTV followed by PTS is suitable for diagnosis and treatment
      of bleeding varices in patients with portal hypertension.

PMID- 23560866
TI  - Ancestral genome organization: an alignment approach.
AB  - We present a comparative genomics approach for inferring ancestral genome
      organization and evolutionary scenarios, based on present-day genomes represented
      as ordered gene sequences with duplicates. We develop our methodology for a model
      of evolution restricted to duplication and loss, and then show how to extend it
      to other content-modifying operations, and to inversions. From a combinatorial
      point of view, the main consequence of ignoring rearrangements is the possibility
      of formulating the problem as an alignment problem. On the other hand,
      duplications and losses are asymmetric operations that are applicable to one of
      the two aligned sequences. Consequently, an ancestral genome can directly be
      inferred from a duplication-loss scenario attached to a given alignment. Although
      alignments are a priori simpler to handle than rearrangements, we show that a
      direct approach based on dynamic programming leads, at best, to an efficient
      heuristic. We present an exact pseudo-boolean linear programming algorithm to
      search for the optimal alignment along with an optimal scenario of duplications
      and losses. Although exponential in the worst case, we show low running times on
      real datasets as well as synthetic data. We apply our algorithm (*) in a
      phylogenetic context to the evolution of stable RNA (tRNA and rRNA) gene content
      and organization in Bacillus genomes. Our results lead to various biological
      insights, such as rates of ribosomal RNA proliferation among lineages, their role
      in altering tRNA gene content, and evidence of tRNA class conversion.

PMID- 23560867
TI  - Function-function correlated multi-label protein function prediction over
      interaction networks.
AB  - Many previous works in protein function prediction make predictions one function
      at a time, fundamentally, which assumes the functional categories to be isolated.
      However, biological processes are highly correlated and usually intertwined
      together to happen at the same time; therefore, it would be beneficial to
      consider protein function prediction as one indivisible task and treat all the
      functional categories as an integral and correlated prediction target. By
      leveraging the function-function correlations, it is expected to achieve improved
      overall predictive accuracy. To this end, we develop a network-based protein
      function prediction approach, under the framework of multi-label classification
      in machine learning, to utilize the function-function correlations. Besides
      formulating the function-function correlations in the optimization objective
      explicitly, we also exploit them as part of the pairwise protein-protein
      similarities implicitly. The algorithm is built upon the Green's function over a
      graph, which not only employs the global topology of a network but also captures
      its local structures. In addition, we propose an adaptive decision boundary
      method to deal with the unbalanced distribution of protein annotation data.
      Finally, we quantify the statistical confidence of predicted functions to
      facilitate post-processing of proteomic analysis. We evaluate the proposed
      approach on Saccharomyces cerevisiae data, and the experimental results
      demonstrate very encouraging results.

PMID- 23560868
TI  - Acquisition and utilisation of anthropometric measurements on admission in a
      paediatric hospital before and after the introduction of a malnutrition screening
      tool.
AB  - BACKGROUND: Acquisition of anthropometric measurements and assessment of growth
      in paediatric inpatients remains poor. The introduction of malnutrition screening
      tools that incorporate weight and height/length measurements might improve their
      acquisition and utilisation in other aspects of patient care. METHODS:
      Documentation of weight and/length measurements and their plotting on growth
      charts was evaluated using a case notes review in paediatric inpatients who were
      admitted before (n = 146), during (n = 154) and after the pilot (n = 151) and
      official (n = 128) clinical use of a screening tool. RESULTS: Documentation of
      weight was high in all periods (> 97% of patients). Height/length measurement
      documentation was negligible (4% of patients) but improved after the introduction
      of the screening tool (> 62%; P < 0.0001), except in infants, who were not part
      of the screening programme. CONCLUSIONS: Introduction of a screening tool
      improved the acquisition of anthropometric measurements by nursing staff,
      although its utilisation by medical staff remained poor.

PMID- 23560869
TI  - The impact of sphincterotome design on selective cannulation of the common bile
      duct.
AB  - BACKGROUND AND AIM: There is a paucity of data regarding the impact of
      sphincterotome design on cannulation success. METHODS: We aimed to compare the
      5.5 F standard sphincterotomes of two different manufacturers (sphincterotome 1:
      Endo-flex 5.5F [ENDO-FLEX GmbH, Voerde, Dusseldorf, Germany] vs sphincterotome 2:
      Ultratome 5.5F [Boston Scientific, Spencer, IN, USA]). Adult patients undergoing
      their first endoscopic retrograde cholangiopancreatography were included in two
      study groups. The sphincterotome preloaded with a guidewire was used for
      selective common bile duct cannulation in each group. Precut methods were applied
      in failed cases without crossover. Successful biliary cannulation in 10 attempts
      was the primary outcome. RESULTS: Baseline features and indications were similar
      between groups (n = 100, group I, sphincterotome 1, vs n = 100, group II,
      sphincterotome 2). A higher success in initial cannulation was obtained in group
      II compared to group I (92% vs 81%, P = 0.03). Moreover, number of cannulation
      attempts and time to cannulation differed. No statistical significance was noted
      in group I (8%) versus group II (3%) regarding pancreatitis rate. The overall
      cannulation success after precut in failed cases was 95% (group I) and 97% (group
      II). CONCLUSIONS: There was a significant difference in cannulation success
      between the two different sphincterotome. 5.5F Ultratome with guidewire was
      superior to 5.5F Endo-flex sphincterotome with guidewire in initial selective
      cannulation of common bile duct. The results may show the importance of
      sphincterotome features to overcome the obstacles during cannulation such as
      complex intrapapillary mucosal features.

PMID- 23560870
TI  - Selective ammonium nitrate recognition by a heteroditopic macrotricyclic ion-pair
      receptor.
AB  - The heteroditopic macrotricyclic molecular receptor 1, which bears a tripodal
      anion binding domain and 4,10,16-triaza-18-crown-6 cation recognition domain,
      proves to be an effective ion-pair receptor. In the absence of the cobound cation
      (TBA(+) salts) receptor 1 preferably binds nitrate and nitrite over other anions,
      including basic anions such as acetate or dihydrogenphosphate. Ammonium cation
      binding by the 4,10,16-triaza-18-crown-6 subunit significantly enhances the
      strength of the nitrate and nitrite complexation at the triamide recognition site
      of the receptor. In the presence of ammonium cations, the association constants
      of nitrate binding reach an impressive value of 1050 M(-1) in highly polar DMSO
      d6. Interestingly, the binding of other anions such as chloride and bromide is
      not enhanced in the presence of a cobound NH4(+) cation. The increased affinity
      of [1.NH4(+)]PF6(-) for anionic species is attributed to a strong cooperative
      effect that arises from the properly positioned binding sites in the receptor 1
      cavity, thus allowing for the formation of the ion pair. Under liquid/liquid
      conditions, receptor 1 is able to extract NH4NO3 from an aqueous to an organic
      phase, as inferred from (1)H NMR spectroscopic and nitrite/nitrate colorimetric
      analyses.

PMID- 23560871
TI  - The 12th International Workshops on Opportunistic Protists (IWOP-12).
AB  - The 12th International Workshops on Opportunistic Protists (IWOP-12) was held in
      August 2012 in Tarrytown, New York. The objectives of the IWOP meetings are to:
      (1) serve as a forum for exchange of new information among active researchers
      concerning the basic biology, molecular genetics, immunology, biochemistry,
      pathogenesis, drug development, therapy, and epidemiology of these
      immunodeficiency-associated pathogenic eukaryotic microorganisms that are seen in
      patients with AIDS and (2) foster the entry of new and young investigators into
      these underserved research areas. The IWOP meeting focuses on opportunistic
      protists, e.g. the free-living amoebae, Pneumocystis, Cryptosporidium,
      Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference
      represents the major conference that brings together research groups working on
      these opportunistic pathogens. Slow but steady progress is being achieved on
      understanding the biology of these pathogenic organisms, their involvement in
      disease causation in both immune-deficient and immune-competent hosts, and is
      providing critical insights into these emerging and reemerging pathogens. This
      IWOP meeting demonstrated the importance of newly developed genomic level
      information for many of these pathogens and how analysis of such large data sets
      is providing key insights into the basic biology of these organisms. A great
      concern is the loss of scientific expertise and diversity in the research
      community due to the ongoing decline in research funding. This loss of
      researchers is due to the small size of many of these research communities and a
      lack of appreciation by the larger scientific community concerning the state of
      art and challenges faced by researchers working on these organisms.

PMID- 23560872
TI  - Comparison of injection dose force, accuracy and precision among three growth
      hormone injection devices.
AB  - Successful growth hormone (GH) therapy requires sustained treatment adherence,
      usually over long periods of time. However, adherence rates are often poor and
      this can lead to suboptimal clinical outcomes. Developments in GH injection
      devices aim to help improve adherence by making daily injections easier.
      Injection force is an important practical aspect for patients receiving daily GH
      injections, particularly for patients with small hands or reduced hand strength
      due to muscle weakness. Norditropin FlexPro (Novo Nordisk A/S, Bagsvaerd,
      Denmark) is an easy-to-use GH injection pen device, shown here to have reduced
      injection force, similar dose accuracy and greater dose precision compared with
      Norditropin NordiFlex (Novo Nordisk A/S) and Genotropin GoQuick (Pfizer Inc., NY,
      USA). Easier injections may enable patients to self-administer GH more readily
      and therefore potentially may help improve adherence and clinical outcome.

PMID- 23560873
TI  - Scoring multipole electrostatics in condensed-phase atomistic simulations.
AB  - Permanent multipoles (MTPs) embody a natural extension to common point-charge
      (PC) representations in atomistic simulations. In this work, we propose an
      alternative to the computationally expensive MTP molecular dynamics simulations
      by running a simple PC simulation and later reevaluate-"score''-all energies
      using the more detailed MTP force field. The method, which relies on the
      assumption that the PC and MTP force fields generate closely related phase
      spaces, is accomplished by enforcing identical sets of monopoles between the two
      force fields-effectively highlighting the higher MTP terms as a correction to the
      PC approximation. We first detail our consistent parametrization of the
      electrostatics and van der Waals interactions for the two force fields. We then
      validate the method by comparing the accuracy of protein-ligand binding free
      energies from both PC and MTP-scored representations with experimentally
      determined binding constants obtained by us. Specifically, we study the binding
      of several arylsulfonamide ligands to human carbonic anhydrase II. We find that
      both representations yield an accuracy of 1 kcal/mol with respect to experiment.
      Finally, we apply the method to rank the energetic contributions of individual
      atomic MTP coefficients for molecules solvated in water. All in all, MTP scoring
      is a computationally appealing method that can provide insight into the
      multipolar electrostatic interactions of condensed-phase systems.

PMID- 23560874
TI  - The evidence of occult hypervolemia; improvement of cardiac functions after
      kidney transplantation.
AB  - The term cardiorenal syndrome (CRS) has been used to define interactions between
      acute or chronic dysfunction of the heart or kidney. When primary chronic kidney
      disease contribute to cardiac dysfunction, it is classified as type 4 CRS.
      Cardiac dilatation, valve regurgitations, and left ventricular dysfunction are
      observed in end-stage renal failure patients with uremic cardiomyopathy. Because
      of perioperative risks in these patients, they may not be considered a candidate
      for kidney transplantation. However, uremic cardiomyopathy can be corrected when
      volume control is achieved by appropriate dose and duration of ultrafiltration.
      By presenting two cases with occult hypervolemia in uremic cardiomyopathy whose
      cardiac functions improved early after kidney transplantation, attention is drawn
      to the importance of kidney transplantation on cardiac function in such patients
      primarily and the importance of strict volume control on cardiac function in
      dialysis patients waiting for kidney transplantation.

PMID- 23560875
TI  - An AUC-based permutation variable importance measure for random forests.
AB  - BACKGROUND: The random forest (RF) method is a commonly used tool for
      classification with high dimensional data as well as for ranking candidate
      predictors based on the so-called random forest variable importance measures
      (VIMs). However the classification performance of RF is known to be suboptimal in
      case of strongly unbalanced data, i.e. data where response class sizes differ
      considerably. Suggestions were made to obtain better classification performance
      based either on sampling procedures or on cost sensitivity analyses. However to
      our knowledge the performance of the VIMs has not yet been examined in the case
      of unbalanced response classes. In this paper we explore the performance of the
      permutation VIM for unbalanced data settings and introduce an alternative
      permutation VIM based on the area under the curve (AUC) that is expected to be
      more robust towards class imbalance. RESULTS: We investigated the performance of
      the standard permutation VIM and of our novel AUC-based permutation VIM for
      different class imbalance levels using simulated data and real data. The results
      suggest that the new AUC-based permutation VIM outperforms the standard
      permutation VIM for unbalanced data settings while both permutation VIMs have
      equal performance for balanced data settings. CONCLUSIONS: The standard
      permutation VIM loses its ability to discriminate between associated predictors
      and predictors not associated with the response for increasing class imbalance.
      It is outperformed by our new AUC-based permutation VIM for unbalanced data
      settings, while the performance of both VIMs is very similar in the case of
      balanced classes. The new AUC-based VIM is implemented in the R package party for
      the unbiased RF variant based on conditional inference trees. The codes
      implementing our study are available from the companion website:
      http://www.ibe.med.uni
      muenchen.de/organisation/mitarbeiter/070_drittmittel/janitza/index.html.

PMID- 23560876
TI  - Simultaneous determination of banned acid orange dyes and basic orange dyes in
      foodstuffs by liquid chromatography-tandem electrospray ionization mass
      spectrometry via negative/positive ion switching mode.
AB  - Simultaneous detection of two classes of dyes possessing different chemical
      properties is difficult. In this study, through negative/positive ion switching
      mode, simultaneous determination of four typical acid orange dyes and three
      typical basic orange dyes was achieved by a single high-performance liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method, and the analytical
      efficiency of multiresidues identification was greatly improved. To enhance
      detection sensitivity, the sample pretreatment conditions and HPLC-MS/MS
      determining conditions were carefully optimized. Under optimal conditions, good
      linearity was obtained over the range of 5-500 MUg L(-1) with a correlation
      coefficient (R(2)) >0.9998. Limits of detection (LODs) and limits of
      quantification (LOQs) of the seven dyes were 0.5-3.0 and 2.0-6.0 MUg kg(-1),
      respectively. The recoveries of the seven dyes in soybean products and marinated
      eggs were 74-126% with relative standard deviations (RSDs) of 2.22-25.4%,
      suggesting the developed method is promising for the accurate quantification of
      the seven dyes at trace levels in foods. 

PMID- 23560877
TI  - Detection of Epstein-Barr virus-specific memory CD4+ T cells using a peptide
      based cultured enzyme-linked immunospot assay.
AB  - Approaches to evaluate T-cell responses to Epstein-Barr virus (EBV) include
      enzyme-linked immunospot (ELISPOT), which quantifies cells capable of immediate
      interferon-gamma secretion upon antigen stimulation. However, evaluation of
      expandable EBV-specific memory T cells in an ELISPOT format has not been
      described previously. We quantified EBV-specific T-cell precursors with high
      proliferative capacity by using a peptide-based cultured interferon-gamma ELISPOT
      assay. Standard and cultured ELISPOT responses to overlapping peptide pools (15
      mers overlapping by 11 amino acids) covering the lytic (BZLF1 and BMRF1) and
      latent (EBNA1, EBNA3a, EBNA3b, EBNA3c, LMP1 and LMP2) EBV proteins were evaluated
      in 20 healthy subjects with remote EBV infection and, for comparison, in four
      solid organ transplant recipients. Cultured ELISPOT responses to both lytic and
      latent EBV antigens were significantly higher than standard ELISPOT responses.
      The distribution of EBV-specific T-cell responses detected in healthy virus
      carriers showed more consistent cultured ELISPOT responses compared with standard
      ELISPOT responses. T-cell responses quantified by cultured ELISPOT were mainly
      mediated by CD4+ T cells and a marked pattern of immunodominance to latent-phase
      antigens (EBNA1 > EBNA3 family antigens > LMP2 > LMP1) was shown. Both the
      magnitude and distribution of EBV-specific T-cell responses were altered in solid
      organ transplant recipients; in particular, cultured ELISPOT responses were
      almost undetectable in a lung-transplanted patient with EBV-associated diseases.
      Analysis of T-cell responses to EBV by ELISPOT assays might provide new insights
      into the pathogenesis of EBV-related diseases and serve as new tools in the
      monitoring of EBV infection in immunocompromised patients.

PMID- 23560879
TI  - Rapid screening of yeast mutants with reporters identifies new splicing
      phenotypes.
AB  - Nuclear precursor mRNA splicing requires the stepwise assembly of a large
      complex, the spliceosome. Recent large-scale analyses, including purification of
      splicing complexes, high-throughput genetic screens and interactomic studies,
      have linked numerous factors to this dynamic process, including a well-defined
      core conserved from yeast to human. Intriguingly, despite extensive studies, no
      splicing defects were reported for some of the corresponding yeast mutants. To
      resolve this paradox, we screened a collection of viable yeast strains carrying
      mutations in splicing-related factors with a set of reporters including
      artificial constructs carrying competing splice sites. Previous analyses have
      indeed demonstrated that this strategy identifies yeast factors able to regulate
      alternative splicing and whose properties are conserved in human cells. The
      method, sensitive to subtle defects, revealed new splicing phenotypes for most
      analyzed factors such as the Urn1 protein. Interestingly, a mutant of PRP8
      specifically lacking an N-terminal proline-rich region stimulated the splicing of
      a reporter containing competing branchpoint/3' splice site regions. Thus, using
      appropriate reporters, yeast can be used to quickly delineate the effect of
      various factors on splicing and identify those with the propensity to regulate
      alternative splicing events.

PMID- 23560878
TI  - A systematic review of the association between obesity and asthma in children.
AB  - AIM: To provide a comprehensive integration of contemporary studies focusing on
      the relationship between obesity and asthma in paediatric populations.
      BACKGROUND: The simultaneous increase in asthma and obesity prevalence has been
      widely discussed over the past 20 years. Although studies have discovered a
      positive correlation between the two, evidence-based findings are needed to
      develop nursing interventions. DESIGN: A quantitative systematic review on the
      literature was conducted from June-December 2011. DATA SOURCES: An electronic
      database search was conducted for studies published between January 1966-May
      2011. Additional articles were identified through the reference lists of reviewed
      papers. REVIEW METHODS: Inclusion/exclusion criteria and quality appraisal were
      applied to ensure research primarily designed to study the relationship between
      obesity and asthma in children was included. RESULTS: The majority of studies
      support a positive association between obesity and asthma in children. Among
      correlates recognized as important effect modifiers, gender was the most
      prominent, with obese girls more likely to have asthma diagnoses than obese boys.
      Scrutinization of covariates in selected studies revealed that most related to
      children's demographic characteristics and were inconsistent across the studies.
      CONCLUSIONS: This review was designed to integrate contemporary scientific
      findings on the association between obesity and asthma by including a large
      number of studies with variant research designs. To identify high-risk groups and
      develop nursing interventions to help children affected by both epidemics, more
      interdisciplinary and well-designed investigations focusing on an expanded
      spectrum of correlates including demographic and behavioural factors are
      warranted.

PMID- 23560881
TI  - Improving the accuracy of chlorophyll fluorescence measurements.

PMID- 23560880
TI  - Does a patient's physical activity predict recovery from an episode of acute low
      back pain? A prospective cohort study.
AB  - BACKGROUND: Advice to remain active and normalisation of activity are commonly
      prescribed in the management of low back pain (LBP). However, no research has
      assessed whether objective measurements of physical activity predict outcome and
      recovery in acute low back pain. METHOD: The aims of this study were to assess
      the predictive relationship between activity and disability at 3 months in a sub
      acute LBP population. This prospective cohort study recruited 101 consenting
      patients with sub-acute LBP (< 6 weeks) who completed the Roland Morris
      Disability Questionnaire (RMDQ), the Visual Analogue Scale, and resumption of
      full 'normal' activity question (Y/N), at baseline and 3 months. Physical
      activity was measured for 7 days at both baseline and at 3 months with an RT3
      accelerometer and a recall questionnaire. RESULTS: Observed and self-reported
      measures of physical activity at baseline and change in activity from baseline to
      3 months were not independent predictors of RMDQ (p > 0.05) or RMDQ change (p >
      0.05) over 3 months. A self-report of a return to full 'normal' activities was
      significantly associated with greater RMDQ change score at 3 months (p < 0.001).
      Paired t-tests found no significant change in activity levels measured with the
      RT3 (p = 0.57) or the recall questionnaire (p = 0.38) from baseline to 3 months.
      CONCLUSIONS: These results question the predictive role of physical activity in
      LBP recovery, and the assumption that activity levels change as LBP symptoms
      resolve. The importance of a patient's perception of activity limitation in
      recovery from acute LBP was also highlighted. TRIAL REGISTRATION: Clinical Trial
      Registration Number, ACTRN12609000282280.

PMID- 23560882
TI  - Attitudes about regulation among direct-to-consumer genetic testing customers.
AB  - INTRODUCTION: The first regulatory rulings by the U.S. Food and Drug
      Administration on direct-to-consumer (DTC) genetic testing services are expected
      soon. As the process of regulating these and other genetic tests moves ahead, it
      is important to understand the preferences of DTC genetic testing customers about
      the regulation of these products. METHODS: An online survey of customers of three
      DTC genetic testing companies was conducted 2-8 months after they had received
      their results. Participants were asked about the importance of regulating the
      companies selling DTC genetic tests. RESULTS: Most of the 1,046 respondents
      responded that it would be important to have a nongovernmental (84%) or
      governmental agency (73%) monitor DTC companies' claims to ensure the consistency
      with scientific evidence. However, 66% also felt that it was important that DTC
      tests be available without governmental oversight. Nearly, all customers favored
      a policy to ensure that insurers and law enforcement officials could not access
      their information. DISCUSSION: Although many DTC customers want access to genetic
      testing services without restrictions imposed by the government regulation, most
      also favor an organization operating alongside DTC companies that will ensure
      that the claims made by the companies are consistent with sound scientific
      evidence. This seeming contradiction may indicate that DTC customers want to
      ensure that they have unfettered access to high-quality information.
      Additionally, policies to help ensure privacy of data would be welcomed by
      customers, despite relatively high confidence in the companies.

PMID- 23560883
TI  - An ex vivo investigation of the effect of the TATE canine elbow arthroplasty
      system on kinematics of the elbow.
AB  - OBJECTIVE: To devise a kinematic technique to objectively ascertain the location
      and orientation of the centre of rotation of the canine elbow and to compare this
      axis following arthroplasty with the first generation TATETM prosthesis in an ex
      vivo model. METHODS: Five pairs of cadaveric forelimbs were obtained and proximal
      limb soft tissues removed. Pin-mounted reflective markers were applied to the
      humerus and ulna. Limbs were mounted on a frame and six trials of the elbow
      manually cycled through its sagittal range of motion captured using 4 Qualisys
      cameras at 120 Hz. Radiography was performed to identify marker position. TATETM
      cartridges were implanted and kinematic analysis repeated. Kinematic data were
      imported into custom software and the three-dimensional joint centre of rotation
      defined using a closed-form solution for absolute orientation. Paired t tests
      were performed to determine if the centre of rotation of the elbow differed
      significantly (P<0.05) pre- and postoperatively and between left and right limbs.
      RESULTS: There was no significant difference in three-dimensional orientation of
      the elbow axis between pre and postoperative measurements or between left and
      right limbs. CLINICAL SIGNIFICANCE: A critical factor in obtaining a successful
      functional outcome following elbow arthroplasty in humans is accurate
      reconstruction of the anatomic centre of rotation. The first generation TATE
      canine elbow arthroplasty cartridge and its instrumentation accurately
      reconstructed the anatomic centre of rotation in 8 of the 10 elbows assessed in
      this ex vivo model.

PMID- 23560884
TI  - Epidural vs. intravenous fentanyl during colorectal surgery using a double-blind,
      double-dummy design.
AB  - BACKGROUND: The overall therapeutic effectiveness of epidural fentanyl vs. the
      intravenous route is controversial. The present work describes a randomized,
      controlled, double-blind, double-dummy study of the intraoperative requirements
      of fentanyl administered by the intravenous or epidural routes during open colon
      surgery. METHODS: Thirty patients were randomized to receive intraoperative
      analgesia with boluses of fentanyl administered by either the epidural or
      intravenous route (2 MUg/kg). The first fentanyl bolus was administered 10 min
      before incision, and repeated boluses were given when mean arterial pressure or
      heart rate increased more than 20% over basal values. General anaesthesia was
      maintained with a propofol infusion. Intraoperative fentanyl and propofol
      requirements, time to awakening, time to analgesia request, and incidence of
      adverse effects were recorded. RESULTS: Median [interquartile range (range)]
      fentanyl requirements in the epidural and intravenous groups were 0.81 [0.65
      (0.47-2.61)] and 2.5 [1.08 (1.07-4.85)] MUg/kg/h, respectively (P < 0.001). The
      epidural group had a shorter time to awakening, with a median of 8 min [4.5 (3
      18)] compared with 20 min [12.5 (7-34)] for the intravenous group (P < 0.001).
      There were no significant differences in propofol requirements. The time to
      analgesia request was also delayed in the epidural group, with a median of 5 h
      [5.5 (1-16)] vs. 2 h [1 (1-5)] when fentanyl was administered intravenously (P <
      0.001). The incidence of adverse effects was similar in both groups. CONCLUSION:
      During major abdominal surgery, epidural administration requires lower doses of
      intraoperative fentanyl when compared with the intravenous route. Epidural
      fentanyl also facilitates early awakening and residual analgesia without
      increasing adverse events.

PMID- 23560885
TI  - Self-assembled monolayers of NH2-terminated thiolates: order, pKa, and specific
      adsorption.
AB  - Self-assembled monolayers (SAMs) of amino-terminated alkanethiols on Au were
      characterized by a combination of electrochemical (LSV, CV, and EIS) and
      spectroscopic (XPS and SER) techniques. Clear correlations were obtained between
      the apparent surface pKa values determined by impedimetric titrations and order
      parameters such as the content of trans conformers in the SAMs. These results
      contrast with previous studies that exhibit dispersions of up to 6 pH units in
      the reported pKa values. In addition, we determined that inorganic and organic
      phosphate species bind specifically to these SAMs mediating adsorption and
      heterogeneous electron transfer of positively charged macromolecules such as
      cytochrome c.

PMID- 23560886
TI  - Cautious application of the hepatorenal syndrome criteria to critically ill
      patients with cirrhosis.

PMID- 23560887
TI  - Dairy food consumption is inversely associated with the risk of the metabolic
      syndrome in Korean adults.
AB  - BACKGROUND: The present study explored the association between dairy food
      consumption and the risk of the metabolic syndrome in Korean adults using the
      most recent nationally representative data. METHODS: The study sample comprised
      4862 Korean adults (>=19 years) who participated in the fifth Korean National
      Health and Nutrition Examination Surveys. Dairy food consumption was assessed
      using a food frequency questionnaire. The metabolic syndrome was defined
      according to the joint interim statement of the International Diabetes Federation
      and the American Heart Association/National Heart, Lung and Blood Institute.
      RESULTS: We found that the prevalence of the metabolic syndrome was significantly
      lower in subjects with higher milk or yogurt consumption (P < 0.0001). Adjusted
      odds ratios (ORs) for abdominal obesity and high fasting glucose were
      significantly lower among subjects in the highest (>= once per day) than in the
      lowest (none or rarely) category of milk consumption after adjusting for
      potential risk factors [OR = 0.68, 95% confidence interval (CI) = 0.50-0.93, P
      for trend = 0.0314; OR = 0.82, 95% CI = 0.65-1.03, P for trend = 0.0233]. The
      adjusted ORs for lower high-density lipoprotein cholesterol was 28% lower among
      subjects in the highest compared to subjects in the lowest category of yogurt
      consumption (OR = 0.72, 95% CI = 0.52-1.00, P for trend = 0.0197). Furthermore,
      higher consumption of milk or yogurt was found to be significantly associated
      with a lower risk of the metabolic syndrome (OR = 0.71, 95% CI = 0.55-0.93, P for
      trend = 0.0066; OR = 0.71, 95% CI = 0.48-1.05, P for trend = 0.0067).
      CONCLUSIONS: High intakes of dairy foods may be associated with a lower risk of
      the metabolic syndrome.

PMID- 23560888
TI  - Using compound-specific stable carbon isotope analysis to trace metabolism and
      trophic transfer of PCBs and PBDEs in fish from an e-waste site, South China.
AB  - Two fish species (mud carp and northern snakehead) forming a predator/prey
      relationship and sediment samples were collected from a pond contaminated by e
      waste. The concentrations and stable carbon isotope ratios (delta(13)C) of
      individual polychlorinated biphenyl (PCB) and polybrominated diphenyl ether
      (PBDE) congeners were measured to determine if compound-specific carbon isotope
      analysis (CSIA) could be used to provide insight into the metabolism and trophic
      dynamics of PCBs and PBDEs. Significant correlations were found in the isotopic
      data of PCB congeners between the sediment and the fish species and between the
      two fish indicating identical origin of PCBs in sediment and fish. Most PCB
      congeners in the fish species were enriched in (13)C compared with the PCB
      congeners in the sediments as a result of isotopic fractionation during the
      metabolism of PCBs in fish. The isotopic data of several PCB congeners showing
      isotopic agreement or isotopic depletion could be used for source apportionment
      or to trace the reductive dechlorination process of PCBs in the environment. The
      PCB isotopic data covaried more in the northern snakehead than in the mud carp
      when compared to the sediment, implying that a similar isotopic fractionation
      occurs from the prey to the predator fish for a PCB congener possibly due to
      similar metabolic pathways. The PBDE congener patterns differed in the three
      sample types with a high abundance of BDE209, 183, 99, and 47 in the sediment,
      BDE47, 153, and 49 in the mud carp and BDE47, 100, and 154 in the northern
      snakehead. The isotopic change of BDE congeners, such as BDE47 and BDE49, in two
      fish species, provides evidence for biotransformation of PBDEs in biota. The
      results of this study suggest that CSIA is a promising tool for deciphering the
      fate of PCBs and PBDEs in the environment.

PMID- 23560890
TI  - The clinical findings and prophylactic treatment in children with factor X
      deficiency.
AB  - Factor X (FX) is the component of both extrinsic and intrinsic coagulation
      cascade and is the first enzyme of the common pathway which results in thrombus.
      Congenital FX deficiency (FXD) is an extremely rare coagulation defect. In this
      study, we aimed to investigate the clinical and laboratory data of the patients
      diagnosed with FXD. The files of the 15 patients (7 female, 8 male) diagnosed and
      followed up for FXD within the last 4 years were evaluated retrospectively. The
      mean age of the patients was 29 months (min-max:1-144 months). The most
      presenting complaints were easy bruisability (n = 8; 53%) and epistaxis (n = 8;
      53%). FX levels were <1% in six patients, 1-5% in four patients, and >5% in five
      patients. Heparin added-Protrombin Complex was used for prophlaxy (n = 11; 73%).
      Any treatment-related complication was not observed. Heparin-added PCC can be
      used safely for effective prophlaxy. We suggest that family history is important
      when considering prophlaxy and in patients with life-threatening bleeding or with
      FXD sibling the prophlaxy should be introduced in the early course. 

PMID- 23560889
TI  - The immature dentate gyrus represents a shared phenotype of mouse models of
      epilepsy and psychiatric disease.
AB  - OBJECTIVES: There is accumulating evidence to suggest psychiatric disorders, such
      as bipolar disorder and schizophrenia, share common etiologies,
      pathophysiologies, genetics, and drug responses with many of the epilepsies.
      Here, we explored overlaps in cellular/molecular, electrophysiological, and
      behavioral phenotypes between putative mouse models of bipolar
      disorder/schizophrenia and epilepsy. We tested the hypothesis that an immature
      dentate gyrus (iDG), whose association with psychosis in patients has recently
      been reported, represents a common phenotype of both diseases. METHODS: Behaviors
      of calcium/calmodulin-dependent protein kinase II alpha (alpha-CaMKII)
      heterozygous knock-out (KO) mice, which are a representative bipolar
      disorder/schizophrenia model displaying iDG, and pilocarpine-treated mice, which
      are a representative epilepsy model, were tested followed by quantitative
      polymerase chain reaction (qPCR)/immunohistochemistry for mRNA/protein expression
      associated with an iDG phenotype. In vitro electrophysiology of dentate gyrus
      granule cells (DG GCs) was examined in pilocarpine-treated epileptic mice.
      RESULTS: The two disease models demonstrated similar behavioral deficits, such as
      hyperactivity, poor working memory performance, and social withdrawal.
      Significant reductions in mRNA expression and immunoreactivity of the mature
      neuronal marker calbindin and concomitant increases in mRNA expression and
      immunoreactivity of the immature neuronal marker calretinin represent iDG
      signatures that are present in both mice models. Electrophysiologically, we have
      confirmed that DG GCs from pilocarpine-treated mice represent an immature state.
      A significant decrease in hippocampal alpha-CaMKII protein levels was also found
      in both models. CONCLUSIONS: Our data have shown iDG signatures from mouse models
      of both bipolar disorder/schizophrenia and epilepsy. The evidence suggests that
      the iDG may, in part, be responsible for the abnormal behavioral phenotype, and
      that the underlying pathophysiologies in epilepsy and bipolar
      disorder/schizophrenia are strikingly similar.

PMID- 23560891
TI  - Endoscopic stapling in comparison to laparoscopic fundoplication for the
      treatment of gastroesophageal reflux disease.
AB  - BACKGROUND: The SRS(TM) Endoscopic Stapling System (Medigus Ltd, Omer, Israel) is
      a novel method for the treatment of gastroesophageal reflux disease (GERD). The
      present study assessed the safety and efficacy of SRS compared with laparoscopic
      anti-reflux surgery (LARS). PATIENTS AND METHODS: Of 27 participants, 11
      underwent SRS and 16 LARS. Symptoms were assessed using Velanovich GERD-health
      related quality of life (GERD-HRQL) scores. The groups were compared in reference
      to operation time, improvement in GERD-HRQL scores, and postoperative course. Chi
      squared and Mann-Whitney-U-tests were used for statistical analysis. RESULTS: Of
      16 (59.3%) male and 11 (40.7%) female patients, mean age was 39.6 (range: 24-60)
      years and mean body mass index was 26.2 kg/m(2) . Both groups were statistically
      similar. An esophageal perforation observed in the SRS group completely recovered
      after over-the-scope clipping. Procedure times for SRSand LARS were 89 and 47
      min, respectively (P < 0.05). Mean discharge time was longer for SRS than LARS (3
      days vs 1.2 days, P < 0.05). However, this difference disappeared with the
      exclusion of a complicated patient with long hospitalization in the SRS group.
      During 6 months mean follow up, proton-pump inhibitor use was insignificantly
      higher in the SRS group (P > 0.05). Mean GERD-HRQL scores dropped in 87% and in
      64% of patients (P > 0.05) from 29.3 to 4.1 and from 24.8 to 8.9 (P = 0.016) in
      LARS and SRS groups, respectively. CONCLUSION: The short-term results of SRS are
      promising. The forthcoming new-generation devices and increasing experience may
      further improve efficacy and decrease untoward effects.

PMID- 23560892
TI  - Treatment of severe rhinophyma using scalpel excision and wire loop tip
      electrosurgery.

PMID- 23560894
TI  - Human mild traumatic brain injury decreases circulating branched-chain amino
      acids and their metabolite levels.
AB  - The pathophysiology of traumatic brain injury (TBI) is complex and not well
      understood. Because pathophysiology has ramifications for injury progression and
      outcome, we sought to identify metabolic cascades that are altered after acute
      human mild and severe TBI. Because catabolism of branched-chain amino acids
      (BCAAs; i.e., valine, isoleucine, and leucine) leads to glucose and energy
      metabolism, and neurotransmitter synthesis and availability, we investigated BCAA
      metabolites in plasma samples collected within 24 h of injury from mild TBI
      (Glasgow Coma Scale [GCS] score >12), severe TBI (GCS <=8), orthopedic injury,
      and healthy volunteers. We report decreased levels of all three BCAAs in patients
      with mild TBI relative to healthy volunteers, while these BCAAs levels in
      patients with severe TBI were further reduced compared with all groups.
      Orthopedic patients exhibited reductions in BCAA comparable to those in patients
      with mild TBI. The decrease in patients with mild and severe TBI persisted for
      derivatives of BCAA catabolic intermediates. Only plasma levels of
      methylglutarylcarnitine, a derivative of a leucine metabolite, were increased in
      patients with severe TBI compared with all other groups. Notably, logistic
      regression combination of three BCAA metabolites whose levels were changed by 24
      h post-injury provided prognostic value (area under the curve=0.92) in
      identifying patients with severe TBI in whom elevated intracranial pressure (>=25
      mm Hg) developed. These changes suggest alteration of BCAA metabolism after TBI
      may contribute to decreased energy production and neurotransmitter synthesis and
      may contribute to TBI pathophysiology. Supplementation of BCAAs and/or their
      metabolites may reduce TBI pathology and improve outcome.

PMID- 23560893
TI  - Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1
      Asian patients retreated with pegylated interferon plus ribavirin.
AB  - BACKGROUND AND AIM: Host interleukin-28B (IL-28B) genetic variants determine a
      sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1)
      treatment-naive patients. Its impact on treatment-experienced Asian patients with
      peginterferon/ribavirin in is to be elucidated. METHODS: IL-28B rs8099917
      genotype was determined in 70 HCV-1 treatment-experienced patients retreated with
      48-week peginterferon/ribavirin. RESULTS: The SVR rate was 60.0% and was
      significantly higher in previous relapsers than in nonresponders (72.7% and
      13.3%, P < 0.001). Multivariate analysis revealed that the most important factor
      predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence
      interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of
      rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to
      patients with TG/GG genotype, those with TT genotype had significantly higher
      rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment
      virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002),
      and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly
      low between previous nonresponders with different rs8099917 genotypes (12.5% vs
      14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had
      a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype
      (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that
      the only factor predictive of an SVR in previous relapsers was the carriage of
      rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014). CONCLUSIONS: Host
      IL-28B genetic variants played a role in Asian relapsers but not nonresponders
      retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly
      avoidable in Asian relapsers with favorable IL-28B genotype.

PMID- 23560895
TI  - Long-term ethanol exposure-induced hepatocellular carcinoma cell migration and
      invasion through lysyl oxidase activation are attenuated by combined treatment
      with pterostilbene and curcumin analogues.
AB  - Ethanol consumption induces hepatocellular carcinoma (HCC) cell metastasis by
      changing the extracellular matrix (ECM). Lysyl oxidase (LOX) catalyzes the cross
      linkage of collagen or elastin in the ECM. LOX protein and mRNA overexpression
      (>21-fold compared with controls, n = 6) was detected in cirrhotic HCC patients
      with a history of alcoholism. LOX protein expression was induced in HCC cells
      after long-term treatment with ethanol (10 mM) for 20-40 passages (denoted E20
      E40 cells). Pterostilbene (PSB, 1 MUM) displayed significant potency to reduce
      LOX-mediated activity in E40 cells when combined with curcumin and its analogues.
      The ability of E40 cells to form colonies in soft agar was reduced by both
      genetic depletion of LOX and by chemical inhibitors of LOX expression. This study
      suggests that targeting LOX expression with food components such as PSB and
      curcumin may be a novel strategy to overcome ethanol-induced HCC cell metastasis
      in liver cancer patients.

PMID- 23560896
TI  - Monoclonal antibody self-association, cluster formation, and rheology at high
      concentrations.
AB  - The rheological properties of macromolecular and colloidal suspensions are
      dependent on the thermodynamic and kinetic parameters that define viscous flow,
      and remain an active field of study with broad implications in cellular
      biophysics, soft-matter theory, and biopharmaceutical technology. Here we use
      static light scattering, small-angle X-ray scattering, and viscosity measurements
      as a function of protein concentration to semiquantitatively correlate the
      oligomeric state of an IgG1 antibody (mAb1) with its rheological behavior at
      solution pH 6.0 and varying ionic strength (modified by 0.01-0.1 M Na2SO4).
      Solution SAXS characterization of 100 mM Na2SO4 solutions confirmed that mAb1
      forms reversible dimers with extended structures in dilute solutions. Light
      scattering measurements over a wide range of concentrations (1-175 mg/mL) provide
      detailed information on the equilibrium thermodynamic mAb1 interactions and their
      modulation by modest increases of Na2SO4. Through the use of interacting hard
      sphere models to fit light-scattering data, we establish that protein cluster
      formations consisting of 2-9 mAb1 molecules also increase the viscosity of 175
      mg/mL IgG solutions from 52 up to 450 cP. The analysis of dilute and semidilute
      mAb1 solution rheology correlates linearly with the thermodynamic equilibrium
      cluster size, consistent with the viscosity behavior of elongated oligomeric
      structures that are not significantly dendrimeric or in a state of globular
      collapse. Furthermore, SAXS- and rheology-based structural modeling illustrate
      that only a small set of anisotropic interactions between complementary surfaces
      are required to nucleate and propagate protein clusters.

PMID- 23560897
TI  - A qualitative review of migrant women's perceptions of their needs and
      experiences related to pregnancy and childbirth.
AB  - AIM: A synthesis of the evidence of migrant women's perceptions of their needs
      and experiences in relation to pregnancy and childbirth. BACKGROUND: Despite the
      fact that all European Union member states have ratified human rights-based
      resolutions aimed at non-discrimination, there is a relationship between social
      inequality and access to pre-, intra-, and postpartum care. DESIGN: A qualitative
      systematic review of studies from European countries. DATA SOURCES: A search was
      made for relevant articles published between January 1996-June 2010. REVIEW
      METHODS: Data were analysed by means of thematic synthesis. RESULTS: Sixteen
      articles were selected, analysed, and synthesized. One overall theme; 'Preserving
      one's integrity in the new country' revealed two key aspects; 'Struggling to find
      meaning' and 'Caring relationships'. 'Struggling to find meaning' comprised four
      sub-themes; 'Communication and connection', 'Striving to cope and manage',
      'Struggling to achieve a safe pregnancy and childbirth', and 'Maintaining bodily
      integrity'. 'Caring relationships' was based on the following three sub-themes:
      'Sources of strength', 'Organizational barriers to maternity care', and 'The
      nature and quality of caring relationships'. CONCLUSION: The results of this
      review demonstrate that migrant women are in a vulnerable situation when pregnant
      and giving birth and that their access to health services must be improved to
      better meet their needs. Research is required to develop continuity of care and
      improve integrated maternal care.

PMID- 23560898
TI  - Bone pain assessment and relationship with parathyroid hormone and health-related
      quality of life in hemodialysis.
AB  - Renal osteodystrophy is a common problem in renal failure patients. Bone pain is
      a common manifestation of renal osteodystrophy. The aim of the study was to
      assess the intensity of chronic bone pain via visual analog scale (VAS) and its
      relationship with parathyroid hormone, health-related quality of life (HRQoL),
      and depression in hemodialysis patients. Ninety-five patients recruited were
      asked to rate chronic bone pain via VAS. Depressive symptoms and HRQoL were
      assessed by Beck Depression Inventory (BDI) and Short-Form 36, respectively. VAS
      was positively correlated with intact parathyroid hormone (r = +0.322, p =
      0.001), phosphorus (r = +0.300, p = 0.003), alkaline phosphatase (r = +0.275, p =
      0.009), and negatively correlated with physical component (r = -0.320, p = 0.002)
      and mental component summary scores (r = -0.247, p = 0.016). In multivariate
      linear regression analysis, logVAS was independently associated with serum
      phosphorus (beta = 0.072, 95% confidence interval: 0.020-0.123, p = 0.007), log
      intact parathyroid hormone (beta = 0.176, 95% confidence interval: 0.041-0.310, p
      = 0.011), and physical component summary score (beta = -0.018, 95% confidence
      interval: -0.031-(-0.005), p = 0.008). VAS is correlated with bone metabolism
      markers, namely, intact parathyroid hormone, and may be used to assess the
      intensity of chronic bone pain. The intensity of chronic bone pain is related
      with HRQoL in hemodialysis patients.

PMID- 23560899
TI  - Letter from Moscow.

PMID- 23560900
TI  - Impervious and intrusive: the impenetrable object in transference and
      countertransference.
AB  - The author describes an internal object that he calls the 'impenetrable object'
      which has two characteristics: being impervious to the projections from the
      patient and being intrusive, i.e. projecting into the patient. It arises out of
      an early relationship with a mother who may be generally disturbed or traumatized
      so that she is unable to take in or tolerate the child's projections and may use
      the child as a receptacle for her own projections. He links the concept of an
      impenetrable object with other concepts such as Williams's 'reversal of the
      container-contained relationship' and Green's 'dead mother'. If such an object
      dominates the patient's internal world, it can lead to severe difficulties in the
      analytic process. Interpretations may be experienced as violent projections from
      the analyst which the patient has to ward off and the analyst may enact an
      impervious or intrusive object in various ways. The author describes a case in
      which such dynamics played a significant role. He argues that intensive work in
      the countertransference is required to detect subtle enactments and allow a shift
      in the analyst, which in turn can enable change in the patient. He gives clinical
      material that demonstrates such work by the analyst and illustrates the shift
      from an impenetrable object to a more permeable one in the patient's internal
      world.

PMID- 23560901
TI  - On psychic elements in a case of autistoid perversion.
AB  - The paper explores the formation of psychic elements from an epistemological
      point of view, drawing on the work of Bion to examine a clinical case of
      autistoid perversion. Distinguishing the qualification of psychic elements from
      the realization of pre-conceptions, the paper argues that psychical elements are
      constituted through a mutually shared experience of presence, and so they should
      be understood in a paradoxical way--through being-O and transformations into K.
      These ideas are explored via a clinical case concerning a patient with an
      autistoid-perverse organization. The patient had been denied any bodily contact
      with her parents during her first year of life due to an infection; in later life
      she exhibited an autistoid coprophilic perversion. During the course of her
      treatment, as it became possible to break down the autistoid organization, the
      nameless contents surfaced in a mutually shared experience of presence. The
      analyst was able to hold on to their meaning, which was unavailable to the
      patient. The absent analyst, however, turned into the mother who 'put the child
      down' and was experienced by the patient as a suicidal threat. In being-O, the
      analyst was able to endure the paradox of being the one who 'put her down' in
      order not to put her down; the paradox of being-O functioned as a container for
      the destructive objectal dimension of the state of 'being put down'.

PMID- 23560902
TI  - The function of the object in the binding and unbinding of the drives.
AB  - The author discusses the clinical consequences of the failure to structure
      ambivalence in terms of a conflict, and explains the paradoxical patterns that
      are then set up, particularly in the various kinds of negative therapeutic
      reaction. He then explores four instances of primary traumatism that contribute
      to the failure of the initial binding of the drives and to the individual's
      subsequent inability to set up a conflict of ambivalence that could curb the
      clinical manifestations of destructiveness.

PMID- 23560903
TI  - The body one has and the body one is: understanding the transsexual's need to be
      seen.
AB  - The transsexual individual confronts the analyst with a disturbing otherness. How
      this otherness is understood, that is, how the analyst 'looks' at the patient
      through her distinctive theoretical lens impacts, in turn, on the patient's
      experience and what transpires between them. In this paper the author outlines a
      developmental model rooted in attachment and object relations theory to provide
      one alternative way of 'looking' at some of these patients' experiences in the
      clinical setting. It is suggested that in some cases of transsexuality the
      primary object(s) did not mirror and contain an early experience of incongruity
      between the given body and the subjective experience of gender: it remains
      unmentalized and disrupts self-coherence leading to the pursuit of surgery that
      is anticipated to 'guarantee' relief from the incongruity. Through an account of
      work with a male to female (MtF) transsexual who underwent surgery during her
      five years of psychotherapy, the author explores how a focus on the transsexual's
      experience of 'being seen', that is, of being taken in (or not) visually and
      mentally by the object in their state of incongruity, affords another window
      through which to approach the transsexual's experience in the transference
      countertransference dynamics.

PMID- 23560904
TI  - The use of child drawings to explore the dual<->group analytic field in child
      analysis.
AB  - Awareness that the child is part of a complex relational system has ensured that
      all child analysts agree on the necessity of establishing a therapeutic alliance
      with the parents. Unconscious conflictual dynamics involve the child analyst and
      include him, from the time of the initial consultation, in an analytic field that
      is closer to that of a group than to the bi-personal set-up of therapy with
      adults. Through a clinical example, the author hypothesizes that the child's
      drawings and play can be viewed as tools capable of mapping the unconscious
      emotions present in an analytic field that extends beyond the analyst-child
      couple. Play and drawings can be used in the relationship with the parents not in
      an explanatory sense, but as a probe with which to explore the universe of
      unconscious emotions present in the group field. The images or the story of the
      play used with this particular modality prove to be an attractive pathway that is
      effective in facilitating the alpha function of each of the members of the group.
      Furthermore, in this sense, they create the conditions for an occasion through
      which the parents can become more aware of their own unconscious emotions that
      have been entrusted to the child and expressed through his symptomatology. The
      possibility for the little group of subjects involved in a child analysis for
      oscillation in a dual-group field permits not only a shared experience of
      knowledge, but also a shared creativity aimed at knowledge of emotional truth
      (O).

PMID- 23560905
TI  - Oedipus the King: quest for self-knowledge--denial of reality. Sophocles' vision
      of man and psychoanalytic concept formation.
AB  - In the Oedipus myth we find a dramatic representation of the child's passionate
      ties to its parents. In the play Oedipus the King, Sophocles relates the theme of
      the myth to the question of self-knowledge. This was the predominant reading in
      German 19th century thinking, and even as a student Freud was fascinated by
      Oedipus' character - not primarily as the protagonist of an oedipal drama, but as
      the solver of divine riddles and as an individual striving for self-knowledge.
      Inspired by Vellacott, Steiner has proposed an alternative reading of Oedipus the
      King as a play about a cover-up of the truth. The text supports both these
      arguments. The pivotal theme of the tragedy is Oedipus' conflict between his
      desire to know himself and his opposing wish to cover up the truth that will
      bring disaster. It is this complex character of Oedipus and the intensity of his
      conflict-ridden struggle for self-knowledge that has made the tragedy to a rich
      source of inspiration for psychoanalytic concept formation and understanding both
      of emotional and cognitive development up to our own time.

PMID- 23560906
TI  - Introduction to Hermann Argelander's paper "The scenic function of the ego and
      its role in symptom and character formation".

PMID- 23560907
TI  - The scenic function of the ego and its role in symptom and character formation.
AB  - The author argues that the scenic function of the ego permits the situationally
      appropriate representation of an unconscious, infantile configuration - that is,
      of a relatively stable, personality-based drive scene having the same status as
      latent dream thoughts. The products of conflict elaboration (symptoms, etc.) are
      manifested in different ways in accordance with the conditions of the relevant
      situation. The contents of the drive scene are created by the psychical apparatus
      on the basis of infantile perceptions and are revealed in screen memories. The
      capacity for situationally appropriate representation is apparently bound up with
      the mobile drive, including its narcissistic transformations. Desexualization (in
      the sense of neutralization) renders scenic elaboration impossible. The drive
      derivatives withdrawn from the scenic configuration contribute to ego
      organization and the formation of character traits, which no longer vary
      according to the situation, but can only be modified by a change in personality
      structure itself. It is as yet unclear whether a process of resexualization can
      make them amenable once more to analytic work. The form of narcissistic libido
      that can assume a scenic configuration is closely related to primary narcissism.
      Its manifestations, which may likewise emerge in situation-dependent symptom
      formations, appear accessible to analysis.

PMID- 23560908
TI  - Discussion of Hermann Argelander's paper: 'The scenic function of the ego and its
      role in symptom and character formation'.

PMID- 23560909
TI  - On: trying to strengthen the psychoanalytic theory and discipline.

PMID- 23560913
TI  - Quantitating the lattice strain dependence of monolayer Pt shell activity toward
      oxygen reduction.
AB  - Lattice strain of Pt-based catalysts reflecting d-band status is the decisive
      factor of their catalytic activity toward oxygen reduction reaction (ORR). For
      the newly arisen monolayer Pt system, however, no general strategy to isolate the
      lattice strain has been achieved due to the short-range ordering structure of
      monolayer Pt shells on different facets of core nanoparticles. Herein, based on
      the extended X-ray absorption fine structure of monolayer Pt atoms on various
      single crystal facets, we propose an effective methodology for evaluating the
      lattice strain of monolayer Pt shells on core nanoparticles. The quantitative
      lattice strain establishes a direct correlation to monolayer Pt shell ORR
      activity.

PMID- 23560912
TI  - Transcriptional and epigenetic signatures of zygotic genome activation during
      early Drosophila embryogenesis.
AB  - BACKGROUND: In all Metazoa, transcription is inactive during the first mitotic
      cycles after fertilisation. In Drosophila melanogaster, Zygotic Genome Activation
      (ZGA) occurs in two waves, starting respectively at mitotic cycles 8
      (approximately 60 genes) and 14 (over a thousand genes). The regulatory
      mechanisms underlying these drastic transcriptional changes remain largely
      unknown. RESULTS: We developed an original gene clustering method based on
      discretized transition profiles, and applied it to datasets from three landmark
      early embryonic transcriptome studies. We identified 417 genes significantly up
      regulated during ZGA. De novo motif discovery returned nine motifs over
      represented in their non-coding sequences (upstream, introns, UTR), three of
      which correspond to previously known transcription factors: Zelda, Tramtrack and
      Trithorax-like (Trl). The nine discovered motifs were combined to scan ZGA
      associated regions and predict about 1300 putative cis-regulatory modules. The
      fact that Trl is known to act as chromatin remodelling factor suggests that
      epigenetic regulation might play an important role in zygotic genome activation.
      We thus systematically compared the locations of predicted CRMs with ChIP-seq
      profiles for various transcription factors, 38 epigenetic marks from ModENCODE,
      and DNAse1 accessibility profiles. This analysis highlighted a strong and
      specific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding
      sites, as well as for histone marks associated with active enhancers (H3K4me1)
      and for open chromatin regions. CONCLUSION: Based on the results of our
      computational analyses, we suggest a temporal model explaining the onset of
      zygotic genome activation by the combined action of transcription factors and
      epigenetic signals. Although this study is mainly based on the analysis of
      publicly available transcriptome and ChiP-seq datasets, the resulting model
      suggests novel mechanisms that underly the coordinated activation of several
      hundreds genes at a precise time point during embryonic development.

PMID- 23560914
TI  - Utilizing Salmonella for antigen delivery: the aims and benefits of bacterial
      delivered vaccination.

PMID- 23560916
TI  - Up to date: comprehensive knowledge of human papillomavirus.
AB  - The 28th International Papillomavirus Conference, hosted by the University of
      Puerto Rico Comprehensive Cancer Center, attracted approximately 1500
      participants from 75 countries. The purpose of the meeting was mainly to provide
      a forum for the exchange of new knowledge; the status of HPV research and its
      future direction and the impact of current strategies for the prevention and
      control of HPV burden and HPV-related conditions. The meeting program consisted
      of a clinical workshop and a public health workshop followed by the main
      conference program. The main conference featured five breakfast sessions, four
      plenary sessions and 22 satellite symposia. Over 800 posters, 167 oral
      presentations and 53 poster-oral presentations were presented. This article
      highlights the most important issues discussed in HPV, which will be of interest
      to those working in the field of HPV vaccines.

PMID- 23560917
TI  - Immune responses to baculovirus-displayed enterovirus 71 VP1 antigen.
AB  - The increased distribution and neurovirulence of enterovirus 71 is an important
      health threat for young children in Asia Pacific. Vaccine design has concentrated
      on inactivated virus with the most advanced undergoing Phase III clinical trials.
      By using a subunit vaccine approach, production costs could be reduced by
      lowering the need for biocontainment. In addition, novel mutations could be
      rapidly incorporated to reflect the emergence of new enterovirus 71
      subgenogroups. To circumvent the problems associated with conventional subunit
      vaccines, the antigen can be displayed on a viral vector that conveys stability
      and facilitates purification. Additional advantages of viral-vectored subunit
      vaccines are their ability to stimulate the innate immune system by transducing
      cells and the possibility of oral or nasal delivery, which dispenses with the
      need for syringes and medical personnel. Baculovirus-displayed VP1 combines all
      these benefits with protection that is as efficient as inactivated virus.

PMID- 23560918
TI  - Recent advances in antibody-inducing poxviral and adenoviral vectored vaccine
      delivery platforms for difficult disease targets.
AB  - Viral vectored vaccine delivery platforms have traditionally been used for the
      induction of cellular rather than humoral immunity. However, in recent years,
      recombinant adenoviral and poxviral vectored vaccines have been optimized to
      induce B-cell responses, resulting in the demonstration of high-titer antibody
      responses in a wide variety of animal species. These approaches have now been
      translated, confirming the induction of substantial levels of antigen-specific
      IgG in a series of Phase I human clinical trials targeting HIV-1 and Plasmodium
      falciparum malaria. To further improve the induction of antibodies, mixed
      modality regimens based on recombinant viral and protein/adjuvant vaccines are
      now being assessed. However, limited data exist about the underlying mechanisms
      mediating the induction of B-cell responses by these subunit vaccines and their
      ability to influence the qualitative aspects of vaccine-induced B-cell
      populations and immunoglobulin. Future studies in this area are needed to guide
      the rational design of antibody-inducing subunit vaccine strategies.

PMID- 23560919
TI  - Development of chimpanzee adenoviruses as vaccine vectors: challenges and
      successes emerging from clinical trials.
AB  - Replication-defective chimpanzee adenovirus vectors are emerging as a promising
      new class of genetic vaccine carriers. Chimpanzee adenovirus vectors have now
      reached the clinical stage and appear to be endowed with all the properties
      needed for human vaccine development, including high quality and magnitude of the
      immune response induced against the encoded antigens, good safety and ease of
      manufacturing on a large-scale basis. Here the authors review the recent findings
      of this novel class of adenovirus vectors and compare their properties to other
      clinical stage vaccine vectors derived from poxvirus, alphavirus and human
      adenovirus.

PMID- 23560920
TI  - Vero cell culture-derived pandemic influenza vaccines: preclinical and clinical
      development.
AB  - Several subtypes of influenza A viruses with pandemic potential are endemic in
      bird populations throughout Asia, Africa and the Middle East, and evidence
      suggests that these viruses are adapting to the mammalian host. As emphasized by
      the high mortality rate of humans infected with H5N1 viruses, this situation
      presents a substantial risk to global human health. The Vero cell culture
      platform has been used to develop whole-virus influenza vaccines that provide
      broad cross-clade protection against viruses with pandemic potential, at low
      antigen doses, without the requirement for adjuvantation. The safety and
      immunogenicity of these vaccines has been demonstrated in studies with more than
      10,000 individuals, including healthy adult and elderly subjects, children and
      various risk groups. These Vero cell-derived vaccines are licensed for
      prepandemic and pandemic use. The Vero platform is also being explored to develop
      next-generation live-attenuated and recombinant vaccines.

PMID- 23560921
TI  - Influenza vaccination in children with cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited autosomal recessive disease characterized by
      progressive pulmonary damage and respiratory failure. It is known that bacterial
      infections play a critical role in the development of significant lung damage,
      whereas the role of respiratory viruses in CF pulmonary exacerbations and the
      relationship between viral infections and the progression of lung damage are
      uncertain. Health authorities throughout the world recommend influenza
      vaccination for CF patients. The aim of this review is to analyze the impact of
      seasonal and pandemic influenza on CF patients and data concerning influenza
      vaccination in order to assess the current situation and identify areas for
      future study. As data are limited, further well-constructed clinical studies of
      the effectiveness of influenza vaccination on the main clinical outcome measures
      of pulmonary function and nutritional status in patients with CF are required.

PMID- 23560922
TI  - Carbohydrate-based Clostridium difficile vaccines.
AB  - Clostridium difficile is responsible for thousands of deaths each year and a
      vaccine would be welcomed, especially one that would disrupt bacterial
      maintenance, colonization and persistence in carriers and convalescent patients.
      Structural explorations at the University of Guelph (ON, Canada) discovered that
      C. difficile may express three phosphorylated polysaccharides, named PSI, PSII
      and PSIII; this review captures our recent efforts to create vaccines based on
      these glycans, especially PSII, the common antigen that has precipitated
      immediate attention. The authors describe the design and immunogenicity of
      vaccines composed of raw polysaccharides and conjugates thereof. So far, it has
      been observed that anti-PSII antibodies can be raised in farm animals, mice and
      hamster models; humans and horses carry anti-PSII IgA and IgG antibodies from
      natural exposure to C. difficile, respectively; phosphate is an indispensable
      immunogenic epitope and vaccine-induced PSII antibodies recognize PSII on C.
      difficile outer surface.

PMID- 23560923
TI  - Why can't we make an effective vaccine against Helicobacter pylori?
AB  - Helicobacter pylori is a major human pathogen that colonizes the stomach and is
      the lead etiological agent for several pathologies. An effective vaccine against
      these bacteria would be invaluable for protecting against gastric adenocarcinoma.
      However, the development of such a vaccine has stalled and the field has
      progressed little in the last decade. In this review, the authors provide an
      opinion on key problems that are preventing the development of a H. pylori
      vaccine. Primarily, this involves the inability to produce a completely
      protective immune response. The knock-on effects of this include a loss of
      industry investment. Overcoming these problems will likely involve defeating the
      immune-evasion defenses of H. pylori, in particular the mechanism(s) by which it
      evades antibody-mediated attack.

PMID- 23560925
TI  - Business travelers: vaccination considerations for this population.
AB  - Illness in business travelers is associated with reduced productivity on the part
      of the employee as well as the employer. Immunizations offer a reliable method of
      preventing infectious diseases for international business travelers. The authors
      review the travel patterns of business travelers, available data on illnesses
      they encounter, their potential travel-associated risks for vaccine-preventable
      diseases and recommendations on immunizations for this population. Routine
      vaccines (e.g., measles, tetanus and influenza) should be reviewed to assure that
      they provide current coverage. The combined hepatitis A and hepatitis B vaccine
      with a rapid schedule offers options for those with time constraints. Other
      vaccine recommendations for business travelers need to focus on their
      destinations and activities and underlying health, taking into account the
      concept of cumulative risk for those with frequent travel, multiple trips or long
      stays.

PMID- 23560924
TI  - The next 10 years for tuberculosis vaccines: do we have the right plans in place?
AB  - The control of TB is a global health priority. Over the last decade, considerable
      progress has been made in the field of TB vaccines with numerous vaccine
      candidates entering the clinic and two candidates now in Phase IIb efficacy
      trials. Nevertheless, the lack of predictive animal models and biomarkers of TB
      vaccine efficacy prevents rational vaccine down-selection and necessitates
      prolonged and expensive clinical efficacy trials in target populations. Advances
      in molecular technology and progress in the development of human as well as
      animal mycobacterial challenge models make the identification of one or more
      immune correlates of protection a genuine prospect over the next decade.
      Moreover, the increasing pace, extent and coordination of global research efforts
      in TB promises to broaden understanding and inform the next generation of vaccine
      candidates against TB as well as related globally important pathogens.

PMID- 23560927
TI  - Regulation of podocalyxin expression in the kidney of streptozotocin-induced
      diabetic rats with Chinese herbs (Yishen capsule).
AB  - BACKGROUND: Diabetic nephropathy is an emergent issue in China with increase in
      patients with type II diabetes. There are several successful Chinese herbal
      products for the treatment of patients with diabetic nephropathy in China.
      However, the mechanisms mediating the biological activity of these products are
      still unclear. Podocalyxin is a sialoprotein critical to maintaining integrity of
      filtration function of glomerulus. METHODS: By employing streptozotocin-induced
      diabetic rats and a Chinese herb formulation (Yishen capsule), we examined the
      regulation of podocalyxin expression in the kidney by Yishen capsule through
      immunofluorescent staining and reverse transcriptase polymerase chain reaction.
      RESULTS: After injection of STZ, there were significant increase in both blood
      glucose and urinary protein. Serum creatinine and BUN were also increased in rats
      with injection of STZ. Moreover, expression of podocalyxin in the glomerulus was
      gradually reduced after injection of STZ. There was also a loss of podocyte foot
      processes in the glomerular basement membrane. However, Yishen capsule or
      benazepril was able to restore the expression of podocalyxin and podocyte foot
      processes in the kidney. Although Yishen capsule could reduce urinary protein
      level, it has little effect on blood glucose level in the rats injected with STZ.
      CONCLUSIONS: Yishen capsule could attenuate the loss of podocalyxin in the
      glomerulus of rats injected with STZ.

PMID- 23560928
TI  - Role of proteoglycans in the regulation of the skeletal muscle fibrotic response.
AB  - Myogenesis consists of a highly organized and regulated sequence of cellular
      processes aimed at forming or repairing muscle tissue. Several processes occur
      during myogenesis, including cell proliferation, migration, and differentiation.
      Cytokines, proteinases, cell adhesion molecules and growth factors are involved,
      either activating or inhibiting these events, and are modulated by a group of
      molecules called proteoglycans (PGs), which play critical roles in skeletal
      muscle physiology. Particularly interesting are some of the factors responsible
      for the fibrotic response associated with skeletal muscular dystrophies.
      Transforming growth factor-beta and connective tissue growth factor have gained
      great attention as factors participating in the fibrotic response in skeletal
      muscle. This review is focused on the advances achieved in understanding the
      roles of proteoglycans as modulators of profibrotic growth factors in fibrosis
      associated with diseases such as skeletal muscle dystrophies. 

PMID- 23560929
TI  - The ability of the Reciproc R25 instrument to reach the full root canal working
      length without a glide path.
AB  - AIM: To assess the frequency in which the Reciproc instrument reaches the full
      working length (FWL) of mandibular molar canals without a glide path.
      METHODOLOGY: From a pool of mandibular molars, 253 root canals were classified as
      straight (G1) and, 249 root canals as moderately curved (G2) following
      Schneider's method. A R25 Reciproc instrument (VDW, Munich, Germany) was advanced
      in the canals without any previous glide path. All cases where Reciproc
      instruments reached the FWL were classified as 'Reaching the FWL' (RFWL). When
      the FWL was not reached by the R25, the root canals were classified as 'Not
      Reaching the FWL' (NRFWL). Pearson's chi(2) test compared (i) the frequency
      distributions of root canals classified as RFWL and NRFWL for each group and (ii)
      the frequency distributions of NRFWL canals between the groups. RESULTS: In G1, 9
      cases (3.56%) and in G2, 23 canals (9.34%) were classified as NRFWL. The
      difference between NRFWL and RFWL was significant in both groups (P = 0.00,
      chi(2) = 217.2 for G1; P = 0.00, chi(2) = 167.8 for G2). The frequency of NRFWL
      was significantly higher for G2 (P = 0.02, chi(2) = 5.452). CONCLUSION: The R25
      Reciproc instrument is able to reach the FWL of straight- and moderate-curved
      mandibular molar canals without a glide path in a large proportion of cases.

PMID- 23560931
TI  - Next-generation sequencing platforms.
AB  - Automated DNA sequencing instruments embody an elegant interplay among chemistry,
      engineering, software, and molecular biology and have built upon Sanger's
      founding discovery of dideoxynucleotide sequencing to perform once-unfathomable
      tasks. Combined with innovative physical mapping approaches that helped to
      establish long-range relationships between cloned stretches of genomic DNA,
      fluorescent DNA sequencers produced reference genome sequences for model
      organisms and for the reference human genome. New types of sequencing instruments
      that permit amazing acceleration of data-collection rates for DNA sequencing have
      been developed. The ability to generate genome-scale data sets is now
      transforming the nature of biological inquiry. Here, I provide an historical
      perspective of the field, focusing on the fundamental developments that predated
      the advent of next-generation sequencing instruments and providing information
      about how these instruments work, their application to biological research, and
      the newest types of sequencers that can extract data from single DNA molecules.

PMID- 23560932
TI  - Scanning electrochemical cell microscopy: a versatile technique for nanoscale
      electrochemistry and functional imaging.
AB  - Scanning electrochemical cell microscopy (SECCM) is a new pipette-based imaging
      technique purposely designed to allow simultaneous electrochemical, conductance,
      and topographical visualization of surfaces and interfaces. SECCM uses a tiny
      meniscus or droplet, at the end of a double-barreled (theta) pipette, for high
      resolution functional imaging and nanoscale electrochemical measurements. Here we
      introduce this technique and provide an overview of its principles,
      instrumentation, and theory. We discuss the power of SECCM in resolving complex
      structure-activity problems and provide considerable new information on electrode
      processes by referring to key example systems, including graphene, graphite,
      carbon nanotubes, nanoparticles, and conducting diamond. The many longstanding
      questions that SECCM has been able to answer during its short existence
      demonstrate its potential to become a major technique in electrochemistry and
      interfacial science.

PMID- 23560933
TI  - Structures of biomolecular ions in the gas phase probed by infrared light
      sources.
AB  - Infrared (IR) spectroscopy of biomolecular ions combines mass spectrometry's high
      sensitivity and ability to analyze complex mixtures with the enhanced structural
      information available from vibrational spectroscopy. IR spectroscopy is in
      principle well placed to distinguish isomers and allow chemical classification of
      unknown molecules. This review gives an outline of current instrumentation,
      spectroscopic approaches, and potential bottlenecks. We discuss the most
      promising applications in bioanalytical mass spectrometry in view of recent
      experimental results, as well as future applications based on bioinformatics.

PMID- 23560935
TI  - Associations between preschoolers' daytime and nighttime sleep parameters by El
      Sheikh, Arsiwalla, Staton, Dyer, and Vaughn.

PMID- 23560936
TI  - A comparison between fixation methods of femoral diaphyseal fractures in cats - a
      retrospective study.
AB  - OBJECTIVES: To compare the outcome of three different fixation methods and to
      determine prognostic factors in cats with diaphyseal femoral fractures. METHODS:
      Retrospective analysis of case records of cats with diaphyseal femoral fractures
      surgically corrected using external fixators, bone plate or plate-rod construct.
      Outcome was evaluated by estimating the time to bone healing and by calculating
      the complication rate. RESULTS: In total, an external fixator was used in 30
      cases, a bone plate in 20 cases and a plate-rod construct in 56 cases. All
      methods were successful in achieving bone healing without significant
      differences. There was a significant difference between the categorized
      complication rates between the treatment groups. The external fixation group had
      the most complications overall. When only the major and catastrophic
      complications were taken into account, it had the fewest complications. The plate
      rod construct had the fewest complications overall, with most being major
      complications. The bone plate group had a complication rate between that of the
      external fixation and plate-rod construct groups. It had the most catastrophic
      complications in relative terms. CLINICAL SIGNIFICANCE: There was no
      statistically significant difference in the time to achieve bone healing but
      there was a significant difference in categorized complication rates between the
      groups.

PMID- 23560930
TI  - Structural glycomic analyses at high sensitivity: a decade of progress.
AB  - The field of glycomics has recently advanced in response to the urgent need for
      structural characterization and quantification of complex carbohydrates in
      biologically and medically important applications. The recent success of
      analytical glycobiology at high sensitivity reflects numerous advances in
      biomolecular mass spectrometry and its instrumentation, capillary and microchip
      separation techniques, and microchemical manipulations of carbohydrate
      reactivity. The multimethodological approach appears to be necessary to gain an
      in-depth understanding of very complex glycomes in different biological systems.

PMID- 23560937
TI  - Relationship between endothelial nitric oxide synthase gene polymorphisms and
      ischemic stroke: a meta-analysis.
AB  - OBJECTIVES: Previous studies examining whether polymorphisms (G894T, 4b/a, and
      T786C) in the endothelial nitric oxide synthase (eNOS) gene are associated with
      ischemic stroke have yielded conflicting results. We performed a meta-analysis to
      investigate the potential association between these three eNOS gene polymorphisms
      and ischemic stroke risk. MATERIALS AND METHODS: We searched databases until
      April 30, 2012 and used fixed or random effects models to estimate the pooled
      odds ratios (ORs). RESULTS: We analyzed 34 case-control data sets from 33
      publications involving 5261/5823 cases/controls for G894T, 4295/4682 for 4b/a,
      and 2698/3254 for T786C polymorphisms. For Asian populations, all models showed
      significantly increased risk of ischemic stroke for the G894T (dominant model: OR
      = 1.58; 95% CI, 1.30-1.91; P = 0.000) and 4b/a polymorphisms (dominant model: OR
      = 1.46; 95% CI, 1.25-1.71; P = 0.000), even after Bonferroni correction (because
      0.000 < 0.017). In white populations, the aa genotype seemed to be protective for
      ischemic stroke, as indicated by the recessive model (OR = 0.44; 95% CI, 0.22
      0.87; P = 0.019). In Asian populations, the T786C polymorphism was significantly
      associated with ischemic stroke, as found using the dominant (OR = 1.17; 95% CI,
      1.02-1.34; P = 0.025) and additive models (OR = 1.18; 95% CI, 1.05-1.33; P =
      0.006). CONCLUSIONS: Our comprehensive meta-analysis ascertains that the G894T,
      4b/a, and T786C polymorphisms are associated with ischemic stroke risk in Asians.
      A possible contrasting role of the 4b/a polymorphism in ischemic stroke was
      indicated in white populations.

PMID- 23560938
TI  - Plasma copeptin, a possible prognostic marker in cirrhosis.
AB  - BACKGROUND & AIM: Copeptin, secreted stoichiometrically with vasopressin,
      demonstrated its prognostic role in various diseases other than cirrhosis.
      METHODS: We investigated the association between severity of cirrhosis and plasma
      concentrations of copeptin, and the prognostic value of copeptin in 95 non-septic
      cirrhotic patients (34 Child-Pugh A, 29 CP-B, 32 CP-C), 30 septic patients with a
      Child-Pugh >8 ('group D'), and 16 healthy volunteers. Patients were followed for
      at least 12 months to assess the composite endpoint death/liver transplantation.
      RESULTS: Median copeptin concentrations (interquartile range) increased through
      healthy volunteers group [5.95 (3.76-9.43) pmol/L] and 'group D' patients [18.81
      (8.96-36.66) pmol/L; P < 0.001)]. During a median follow-up of 11.0 +/- 6.1
      months, 28 non-transplanted patients died and eight were transplanted. In
      receiver operated characteristic curves analysis, the area under the curve values
      were as follows: Child-Pugh score 0.80 (95% CI: 0.71-0.86), model of end-stage
      liver disease (MELD) score 0.80 (0.70-0.86), C-reactive protein (CRP) 0.71 (0.60
      0.80) and copeptin 0.70 (0.57-0.79). By stratifying the values of these variables
      into tertiles, the risk of death/liver transplantation for patients belonging to
      the highest tertile of copeptin (>13 pmol/L) was high (Log-rank test: P = 0.0002)
      and 2.3-fold higher than for patients with lower concentrations after adjusting
      for MELD score (>21) and CRP (>24 mg/L) in a Cox model. Other potential
      predictors (age, total cholesterol, natraemia and serum free cortisol) did not
      reach a significant level. CONCLUSION: In cirrhotic patients, copeptin
      concentrations increased along with the severity of liver disease. In our cohort,
      the 1-year mortality or liver transplantation was predicted by high MELD score
      and high concentrations of CRP and copeptin.

PMID- 23560939
TI  - Motor cortex plasticity induced by theta burst stimulation is impaired in
      patients with obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is a respiratory condition occurring during sleep
      characterised by repeated collapse of the upper airway. Patients with OSA show
      altered brain structure and function that may manifest as impaired
      neuroplasticity. We assessed this hypothesis in 13 patients with moderate-to
      severe OSA and 11 healthy control subjects. Transcranial magnetic stimulation was
      used to induce and measure neuroplastic changes in the motor cortex by assessing
      changes in motor-evoked potentials (MEPs) in a hand muscle. Baseline measurements
      of cortical excitability included active (AMT) and resting motor thresholds
      (RMT), and the maximal stimulator output producing a 1-mV MEP. Intracortical
      inhibition (ICI) was investigated with short- and long-interval ICI paradigms
      (SICI and LICI, respectively), and neuroplastic changes were induced using
      continuous theta burst stimulation (cTBS). At baseline, differences were found
      between groups for RMT (9.5% maximal stimulator output higher in OSA) and 1-mV
      MEPs (10.3% maximal stimulator output higher in OSA), but not AMT. No differences
      were found between groups for SICI or LICI. The response to cTBS was different
      between groups, with control subjects showing an expected reduction in MEP
      amplitude after cTBS, whereas the MEPs in patients with OSA did not change. The
      lack of response to cTBS suggests impaired long-term depression-like
      neuroplasticity in patients with OSA, which may be a consequence of sleep
      fragmentation or chronic blood gas disturbance in sleep. This reduced
      neuroplastic capacity may have implications for the learning, retention or
      consolidation of motor skills in patients with OSA.

PMID- 23560940
TI  - Computer simulation of the pneumatic separator in the pneumatic-electrostatic
      separation system for recycling waste printed circuit boards with electronic
      components.
AB  - Technologies could be integrated in different ways into automatic recycling lines
      for a certain kind of electronic waste according to practical requirements. In
      this study, a new kind of pneumatic separator with openings at the dust hooper
      was applied combing with electrostatic separation for recycling waste printed
      circuit boards. However, the flow pattern and the particles' movement behavior
      could not be obtained by experimental methods. To better control the separation
      quantity and the material size distribution, computational fluid dynamics was
      used to model the new pneumatic separator giving a detailed understanding of the
      mechanisms. Simulated results showed that the tangential velocity direction
      reversed with a relatively small value. Axial velocity exhibited two sharp
      decreases at the x axis. It is indicated that the bottom openings at the dust
      hopper resulted in an enormous change in the velocity profile. A new phenomenon
      that was named dusting was observed, which would mitigate the effect of particles
      with small diameter on the following electrostatic separation and avoid materials
      plugging caused by the waste printed circuit boards special properties
      effectively. The trapped materials were divided into seven grades. Experimental
      results showed that the mass fraction of grade 5, grade 6, and grade 7 materials
      were 27.54%, 15.23%, and 17.38%, respectively. Grade 1 particles' mass fraction
      was reduced by 80.30% compared with a traditional separator. Furthermore, the
      monocrystalline silicon content in silicon element in particles with a diameter
      of -0.091 mm was 18.9%, higher than that in the mixed materials. This study could
      serve as guidance for the future material flow control, automation control, waste
      recycling, and semiconductor storage medium destruction.

PMID- 23560941
TI  - Cardiac tamponade may be the first symptom of leukemia.

PMID- 23560942
TI  - Clinical evaluation of a prototype multi-bending peroral direct cholangioscope.
AB  - BACKGROUND: Although peroral direct cholangioscopy (PDCS) is emerging as an
      alternative to traditional mother-daughter cholangioscopy, it is associated with
      high failure rates. The aim of the present study was to evaluate the ability to
      insert and carry out interventions using a prototype multi-bending PDCS. PATIENTS
      AND METHODS: Prospective, observational clinical feasibility study was done in 41
      patients with a variety of biliary diseases. A multi-bending PDCS prototype was
      inserted using a free-hand technique, a guidewire alone, or with a 5-Fr diameter
      anchoring balloon. Diagnostic and therapeutic procedures were carried out.
      RESULTS: The free-hand direct insertion technique failed in all attempted cases
      (n = 7). Of the remaining 34 cases, successful rate of PDCS insertion into the
      distal bile duct was achieved by passing the PDCS over a guidewire alone (n = 6)
      and/or with a guidewire plus anchoring balloon (n = 28) for an overall
      successrate of 88.2% (30/34). In 13 (92.9%) patients without an underlying
      biliary stricture, PDCS insertion proximal to the bifurcation was possible. In 25
      cases, biliary interventions were attempted including biopsy (n = 13), stone
      removal (n = 6), stent removal (n = 1), and intraductal electrohydraulic
      lithotripsy (n = 2) and were successful in 22 (88%). Other than two patients with
      procedure-related cholangitis with a mild grade of severity, no complications
      were observed. CONCLUSIONS: Using a novel multi-bending prototype peroral direct
      cholangioscope, cholangioscopy had a high diagnostic and therapeutic success rate
      only when passed over a guidewire and anchoring balloon but not with the free
      hand insertion technique. Comparative studies of direct cholangioscopy are
      warranted.

PMID- 23560943
TI  - Correlates of urinary incontinence during the menopausal transition and early
      postmenopause: observations from the Seattle Midlife Women's Health Study.
AB  - BACKGROUND: Urinary incontinence (UI) becomes more prevalent as women age, but
      little is known about UI in midlife, including stress incontinence (SUI) and urge
      incontinence (UUI) and their relationship to reproductive aging, reproductive
      history, health-related factors, and personal and social factors associated with
      midlife. OBJECTIVES: To determine the influence of age and reproductive aging
      factors (menopausal transition stages, follicle stimulating hormone (FSH),
      estrone glucoronide), reproductive history (number of live births), health
      related factors (perceived health, body mass index (BMI), exercise, diabetes) and
      personal and social factors (race/ethnicity, education) on the experience of UI
      among midlife women during the menopausal transition and early postmenopause.
      METHODS: A subset of the Seattle Midlife Women's Health Study participants (n =
      298 with up to 2249 observations) provided data during the late reproductive,
      early and late menopausal transition stages and early postmenopause, including
      menstrual calendars, annual health questionnaire and provided health diaries
      since 1990. Generalized estimating equation analysis was used to test models
      accounting for SUI and UUI that included age as a measure of time with
      predictors. RESULTS: Stress urinary incontinence was associated significantly
      with individual predictors of: worse perceived health (odds ratio (OR) 0.89, p =
      0.025), history of >= three live births (OR 3.00, p = 0.002), being in the early
      menopausal transition stage (OR 1.53, p = 0.06), having less formal education (OR
      0.33, p = 0.02), and being White/not Black (OR 0.32, p = 0.04). The most
      parsimonious model for SUI included: worse perceived health, >= three live
      births, and being White. Urge incontinence was associated significantly with
      individual predictors of: increasing age (OR 1.06, p = 0.001), worse perceived
      health (OR 0.78, p < 0.001), BMI >= 30 kg/m(2) (OR 2.96, p = 0.001), history of
      >= three live births (OR 2.81, p = 0.01), and lower FSH levels (OR 0.59, p =
      0.08). The most parsimonious model for UUI included: being older, having worse
      perceived health, and having a high BMI. CONCLUSIONS: SUI risk was a function of
      reproductive history, poor health, and being White. UUI risk was a function of
      aging, having worse health, and higher BMI. Further exploration of UI during the
      menopausal transition is needed to articulate a lifespan view of UI and its
      typology.

PMID- 23560944
TI  - Synergistic interactions between grafted hyaluronic acid and lubricin provide
      enhanced wear protection and lubrication.
AB  - Normal (e.g., adhesion) and lateral (friction) forces were measured between
      physisorbed and chemically grafted layers of hyaluronic acid (HA), an anionic
      polyelectrolyte in the presence of lubricin (Lub), a mucinous glycoprotein, on
      mica surfaces using a surface forces apparatus (SFA). This work demonstrates that
      high friction coefficients between the surfaces do not necessarily correlate with
      surface damage and that chemically grafted HA acts synergistically with Lub to
      provide friction reduction and enhanced wear protection to the surfaces. Surface
      immobilization of HA by grafting is necessary for such wear protection.
      Increasing the concentration of Lub enhances the threshold load that a chemically
      grafted HA surface can be subjected to before the onset of wear. Addition of Lub
      does not have any beneficial effect if HA is physisorbed to the mica surfaces.
      Damage occurs at loads less than 1 mN regardless of the amount of Lub, indicating
      that the molecules in the bulk play little or no role in protecting the surfaces
      from damage. Lub penetrates into the chemically bound HA to form a visco-elastic
      gel that reduces the coefficient of friction as well as boosts the strength of
      the surface against abrasive wear (damage).

PMID- 23560945
TI  - Single-treatment resolution of vascular blebs within port wine stains using a
      novel 1,064-nm neodymium-doped yttrium aluminum garnet laser.

PMID- 23560946
TI  - Single intravitreal ranibizumab injection for optic disc neovascularisation due
      to possibly traumatic, direct carotid cavernous fistula.
AB  - We report a patient with optic disc neovasculariation due to possibly traumatic
      direct carotid cavernous fistula treated by a single dose of intravitreal
      ranibizumab prior to neurointervention. A 25-year-old man had a 10-month history
      of bilateral proptosis and left sixth nerve paralysis was evaluated. Conjunctival
      vessels were markedly dilated, especially in the left eye. Clinical examination
      and fundus fluorescein angiography revealed disc neovascularisation in the left
      eye with subtle peripheral retinal ischaemia. Magnetic resonance imaging
      suggested a high-flow carotid cavernous fistula on the left side and this was
      confirmed by catheter angiography. A single dose of intravitreal ranibizumab was
      injected prior to neuro-intervention. The disc neovascularisation regressed
      completely three days later. The left direct carotid cavernous fistula was later
      treated successfully with coil embolisation. Optic disc neovascularisation is a
      very rare feature of carotid cavernous fistula and intravitreal ranibizumab may
      be a useful therapeutic adjunct prior to neuro-interventional techniques to
      reduce neovascularisation-induced haemorrhage following the intervention. 

PMID- 23560947
TI  - Subjective, but not objective, lingering effects of multiple past concussions in
      adolescents.
AB  - The existing literature on lingering effects from concussions in children and
      adolescents is limited and mixed, and there are no clear answers for patients,
      clinicians, researchers, or policy makers. The purpose of this study was to
      examine whether there are lingering effects of past concussions in adolescent
      athletes. Participants in this study included 643 competitive Bantam and Midget
      hockey players (most elite 20% by division of play) between 13 and 17 years of
      age (mean age=15.5, SD=1.2). Concussion history at baseline assessment was
      retrospectively documented using a pre-season questionnaire (PSQ), which was
      completed at home by parents and players in advance of baseline testing. Players
      with English as a second language, self-reported attention or learning disorders,
      a concussion within 6 months of baseline, or suspected invalid test profiles were
      excluded from these analyses. Demographically adjusted standard scores for the
      five composites/domains and raw symptom ratings from the brief Immediate Post
      Concussion Assessment and Cognitive Testing (ImPACT) computerized battery were
      analyzed. Adolescent athletes with one or two or more prior concussions did not
      have significantly worse neurocognitive functioning on ImPACT than did those with
      no previous concussions. There were significantly more symptoms reported in those
      with two or more prior concussions than in those with no or one prior concussion.
      Adolescents with multiple previous concussions had higher levels of baseline
      symptoms, but there were not group differences in neurocognitive functioning
      using this brief computerized battery.

PMID- 23560948
TI  - Rapid characterization of wheat low molecular weight glutenin subunits by
      ultraperformance liquid chromatography (UPLC).
AB  - Low molecular weight glutenin subunits (LMW-GS), as important seed storage
      proteins, together with HMW-GS significantly define unique dough viscoelastic
      properties. In this study, a rapid ultraperformance liquid chromatography (UPLC)
      method for the separation and characterization of LMW-GS in wheat was optimized
      and established. The fast, reproducible, and high-resolution UPLC separation of
      LMW-GS could be obtained by gradually increasing eluting gradient from 21 to 47%
      in 30 min at flow rate of 0.55 mL/min and 60  degrees C for separation
      temperature. By this method, analysis of one sample could be completed in <20
      min, significantly less time than the traditional reversed-phase high-performance
      liquid chromatography (RP-HPLC) method. Under the optimized conditions, the
      genetic features of LMW-GS and genotype * environmental interaction were
      successfully analyzed, leading to a fast identification of 17 main LMW-GS alleles
      that were related to different quality properties in wheat. The results
      demonstrated that UPLC could be a powerful and alternative tool for genetic and
      proteomic studies of wheat grain proteins and fast identification or screening of
      desirable LMW-GS alleles in wheat quality improvement. 

PMID- 23560949
TI  - Microarray analysis of altered gene expression and the role of ATF3 in HK-2 cells
      treated with hemin.
AB  - OBJECTIVE: To identify gene expression changes and the role of activating
      transcription factor 3 (ATF3) in hemin toxicity in renal tubular epithelial
      cells, then elucidate molecular mechanisms of hemin toxicity on renal tubular
      epithelial cells. METHODS: An oligo array comprising 35,035 genes was used to
      compare differential gene expression in hemin-treated and non-treated HK-2 cells
      (human renal proximal tubular epithelial cells), and the role of ATF3 in hemin
      toxicity was assessed using siRNA technique. RESULTS: A total of 128 mRNAs were
      at least twofold up-regulated and 101 mRNAs were at least twofold down-regulated
      after hemin treatment. Expression levels of ATF3, heat shock protein 70, c-fos,
      and c-jun were remarkably increased. Hemin also suppressed nuclear factor-kappa B
      inhibitor alpha, beta-2 adrenergic receptor, and interleukin-6 mRNA amounts more
      than twofold. We further demonstrated the protective role of ATF3 in hemin
      cytotoxicity. CONCLUSIONS: The data suggest that hemin caused multiple changes of
      gene expression in HK-2 cells, and ATF3 protects against hemin cytotoxicity.

PMID- 23560950
TI  - Enhancing parents' confidence to care in acute childhood illness: triangulation
      of findings from a mixed methods study of Community Children's Nursing.
AB  - BACKGROUND: Children's emergency hospital use is of concern internationally, but
      there has been little examination of home care by nurses. AIMS: To examine the
      care provided by community children's nurses during acute illness. DESIGN:
      Triangulation of findings from case studies of three Community Children's Nursing
      Teams. METHODS: Parents or carers (n = 763) completed questionnaires between 2008
      2010 about their contacts with nurses and satisfaction with aspects and overall
      assessment of nursing care provided. Eighty-one individuals participated in semi
      structured interviews: 29 parents/carers described their experiences and
      explained their questionnaire responses in more detail; 13 children talked about
      their care both in hospital and at home; and 39 nurses and other healthcare
      providers explained how nurses supported care of children at home. Questionnaire
      data were analysed descriptively and interview data qualitatively. The findings
      were integrated by triangulation of methods (questionnaires and interviews) and
      of data from different informants (children, parents, healthcare providers).
      RESULTS: Nursing care most frequently took the form of advice and education by
      either home visits or telephone contact. Parents and children were reassured by
      access to nurses and it gave them confidence to care at home. Most respondents
      thought that it reduced the time their children spent in hospital. CONCLUSIONS:
      Nurses can make an important contribution to supporting parents to care
      confidently for their children at home to reduce or even to avoid hospitalization
      for acute conditions and give them confidence to manage future episodes of
      illness.

PMID- 23560951
TI  - Population responses of small mammals to food supply and predators: a global meta
      analysis.
AB  - 1. The relative importance of food supply and predation as determinants of animal
      population density is a topic of enduring debate among ecologists. To address it,
      many studies have tested the potential effects of food on population density by
      experimentally supplementing natural populations, with much focus on terrestrial
      vertebrates, especially small mammals. 2. Here we perform a meta-analysis of such
      experiments, testing two complementary hypotheses: (i) small mammal populations
      are bottom-up limited and (ii) population increases in response to food
      supplementation are constrained by predation, a top-down limitation. 3. In the
      148 experiments recorded, food supplementation had an overall positive and
      significant effect, increasing population densities by 1.5-fold. Larger
      population increases occurred when predation was reduced and populations were
      open to immigration. Predation appeared to be unimportant when populations were
      closed to immigration. Immigration was the major mechanism underlying increases
      in abundance by increasing local population density and crowding. Contributions
      of increased reproductive rate could be detected, but were minor compared to
      immigration, and no effects were detected from survival. 4. Our analyses support
      the view that animal population density is determined by both bottom-up and top
      down forces. They also suggest the possibility that food supplementation
      experiments might unintentionally create ecological traps by aggregating both
      prey and predators in small areas of the landscape. We suggest an alternative
      experimental design to increase the contribution that food supplementation
      experiments can make in future.

PMID- 23560953
TI  - The America Invents Act implementation.
AB  - The Leahy-Smith America Invents Act (AIA) is by far the most comprehensive change
      to the patent law in at least half a century. Implementation of the AIA has been
      ongoing, but the final and most critical provisions went into effect on March 16,
      2013. Although, it will take several years before we fully understand the law's
      impact, the new law is likely to fundamentally change the way innovation is
      protected within the United States. Researchers will need to become increasingly
      vigilant as to publication dates as well as communications coming from their
      labs.

PMID- 23560955
TI  - Nostradamus in a tube of blood?

PMID- 23560952
TI  - Multi-target action of the novel anti-Alzheimer compound CHF5074: in vivo study
      of long term treatment in Tg2576 mice.
AB  - BACKGROUND: Alzheimer disease is a multifactorial disorder characterized by the
      progressive deterioration of neuronal networks. The pathological hallmarks
      includes extracellular amyloid plaques and intraneuronal neurofibrillary tangles,
      but the primary cause is only partially understood. Thus, there is growing
      interest in developing agents that might target multiple mechanisms leading to
      neuronal degeneration. CHF5074 is a nonsteroidal anti-inflammatory derivative
      that has been shown to behave as a gamma-secretase modulator in vitro and to
      inhibit plaque deposition and to reverse memory deficit in vivo in transgenic
      mouse models of Alzheimer's disease (AD). In the present study, the effects of a
      long-term (13-month) treatment with CHF5074 on indicators of brain functionality
      and neurodegeneration in transgenic AD mice (Tg2576) have been assessed and
      compared with those induced by a prototypical gamma-secretase inhibitor (DAPT).
      RESULTS: To this end, plaque-free, 6-month-old Tg2576 mice and wild-type
      littermates were fed with a diet containing CHF5074 (125 and 375 ppm/day), DAPT
      (375 ppm/day) or vehicle for 13 months. The measured indicators included object
      recognition memory, amyloid burden, brain oligomeric and plasma Abeta levels,
      intraneuronal Abeta, dendritic spine density/morphology, neuronal cyclin A
      positivity and activated microglia. Tg2576 mice fed with standard diet displayed
      an impairment of recognition memory. This deficit was completely reverted by the
      higher dose of CHF5074, while no effects were observed in DAPT-treated mice.
      Similarly, amyloid plaque burden, microglia activation and aberrant cell cycle
      events were significantly affected by CHF5074, but not DAPT, treatment. Both
      CHF5074 and DAPT reduced intraneuronal Abeta content, also increasing Abeta40 and
      Abeta42 plasma levels. CONCLUSIONS: This comparative analysis revealed a
      profoundly diverse range of clinically relevant effects differentiating the
      multifunctional anti-inflammatory derivative CHF5074 from the gamma-secretase
      inhibitor DAPT and highlighted unique mechanisms and potential targets that may
      be crucial for neuroprotection in mouse models of AD.

PMID- 23560956
TI  - Managing the function of the emergency department: Is it time to define what we
      do and how to teach it?

PMID- 23560957
TI  - Stroke thrombolysis and the third international stroke trial: examining 'the
      totality of the evidence'.

PMID- 23560958
TI  - Why is improving pain care so hard?

PMID- 23560959
TI  - Palliative care in the emergency department.

PMID- 23560960
TI  - Review article: Paramedic education opportunities and challenges in Australia.
AB  - Paramedic education has been undergoing major development in Australia in the
      past 20 years, with many different educational programmes being developed across
      all Australian jurisdictions. This paper aims to review the current paramedic
      education programmes in Australia to identify the similarities and differences
      between the programmes, and the strengths and challenges in these programmes. A
      literature search was performed using six scientific databases to identify any
      systematic reviews, literature reviews or relevant articles on the topic.
      Additional searches included journal articles and text references from 1995 to
      2011. The search was conducted during December 2010 and November 2011. Included
      in this review are a total of 28 articles, which are focused around five major
      issues in paramedic education: (i) principle on paramedic programmes and the
      involvement of industry partners; (ii) clinical placements; (iii) contemporary
      methods of education; (iv) needs for specific programmes within paramedic
      education; and (v) articles related to the accreditation process for paramedic
      programmes. Paramedic programmes across Australian universities vary with many
      different practices, especially relating to clinical placements in the field. The
      further advances of the paramedic education programmes should aim to respond to
      population change and industry development, which would enhance the paramedic
      profession across Australia.

PMID- 23560961
TI  - National project seeking to improve pain management in the emergency department
      setting: findings from the NHMRC-NICS National Pain Management Initiative.
AB  - OBJECTIVES: The National Pain Management Initiative was established by the
      National Institute of Clinical Studies to improve analgesic practice across
      Australian EDs. METHODS: A barrier analysis provided information to better
      implement changes in analgesic practice. A working party was established and
      developed a multifaceted intervention strategy and clinical indicators. An online
      data collection system was developed and sites collected data at three monthly
      intervals for 18 months. A stepped-wedge design was chosen to manage the number
      of hospitals involved. Clinical indicators included documentation of pain score,
      time to analgesia, appropriate use of parenteral narcotics and effectiveness of
      analgesia for severe pain. RESULTS: A total of 16,627 patient datasets were
      entered from 45 metropolitan and regional hospitals. There was an increase from
      41% to 64% in documented pain score (difference in proportions 23%, 95%
      confidence interval: 20-26) and median time to analgesia fell from 61 min
      (interquartile range: 23-122) to 41 min (interquartile range: 15-95). Appropriate
      parenteral narcotic use was over 90% for all time points combined. For all
      patients with severe pain there was no significant change in the proportion with
      a documented reduction of pain within 1 h of presentation. CONCLUSION:
      Significant improvements in documentation of pain score and time to analgesia
      were demonstrated through a national project of targeted improvement. Parenteral
      narcotic use has a high level of adherence to recommended practice. An
      improvement in the effectiveness of analgesia in severe pain has not been clearly
      demonstrated in this study.

PMID- 23560962
TI  - Outcomes in older patients requiring comprehensive allied health care prior to
      discharge from the emergency department.
AB  - OBJECTIVES: There is increasing focus on use of multidisciplinary services within
      the ED to facilitate discharge of older patients that might otherwise require
      hospitalisation. The risks associated with this are not well established. We
      aimed to determine whether older patients requiring allied health-facilitated
      discharge from the ED were at increased risk of hospital readmission and death
      after discharge. METHODS: A prospective comparative study with matched controls.
      Patients aged 65 years and over presenting to the ED underwent risk screening.
      Those with a positive screen formed the intervention group and received
      comprehensive allied health input from a care coordination team (CCT) prior to
      discharge. We prospectively enrolled 1098 patients to the intervention group and
      matched these 1:1 with controls deemed low risk on risk screening. The primary
      outcome measure was ED re-attendance within 28 days. Patients were followed up
      for a minimum of 1 year for other outcomes. RESULTS: At 28 days, there was a 3%
      absolute difference in the re-attendance rate to ED (17.9% cases, 14.8% controls,
      P = 0.05) and no mortality difference (1.4% cases, 1.3% controls, P = 0.85). At 1
      year, cases had a higher incidence of unplanned hospitalisation (43.4% vs 29.5%,
      P < 0.001) but not death (10.7% vs 10.2%, P = 0.66). CONCLUSIONS: Facilitated
      discharge of selected older adults by a CCT is relatively safe in the short term.
      Such patients have an increased likelihood of hospitalisation in the year after
      discharge. The 1 year mortality rate even in a 'low-risk' discharged population
      is 10%.

PMID- 23560963
TI  - Common laboratory tests predict imminent medical emergency team calls, intensive
      care unit admission or death in emergency department patients.
AB  - OBJECTIVE: To estimate the ability of commonly measured laboratory variables to
      predict imminent (within the same or next calendar day) medical emergency team
      (MET) calls, ICU admission or death. METHODS: We performed a retrospective
      observational study of ED patients. We estimated the ability of each laboratory
      variable or combination of variables together with patient age to predict
      imminent MET calls, ICU admission or death. We externally validated our findings
      in patients from a different hospital. RESULTS: We studied 160 341 batches in 71
      453 ED patients (average age: 59.9 +/- 22.1 years) for a total of 1 million
      individual measurements. There were 341 MET calls, 160 ICU admissions from the
      wards and 858 deaths. Multivariable modelling achieved a receiver operating
      characteristic area under the curve (ROC-AUC) of 0.69 (95% CI 0.63-0.74) for
      imminent MET call with prediction occurring a mean of 11.9 h before the call.
      Additionally, it achieved a ROC-AUC of 0.82 (95% CI 0.73-0.87) for imminent ICU
      admission. Finally, it achieved a ROC-AUC of 0.90 (95% CI 0.87-0.91) for imminent
      death. When tested using an additional 37 367 batches from a cohort of 21 430 ED
      patients from a second teaching hospital, the multivariate model achieved a ROC
      AUC of 0.70 (95% CI 0.66-0.73) for imminent MET call, a ROC-AUC of 0.84 (95% CI
      0.78-0.90) for imminent ICU admission. Finally, it achieved a ROC-AUC of 0.89
      (95% CI 0.86-0.91) for imminent death. CONCLUSIONS: Commonly performed laboratory
      tests can help predict imminent MET calls, ICU admission or death in ED patients.
      Prospective investigations of the clinical utility of such predictions appear
      desirable.

PMID- 23560964
TI  - Early emergency department representations.
AB  - OBJECTIVE: The present study aims to describe early ED representation rates and
      identify the causes for this commonly seen problem. METHODS: This was a
      retrospective chart review of all patients that represented within 72 h of
      discharge from a tertiary level ED in Sydney, Australia, over a 2 month period
      between 1 May 2010 and 30 June 2010. Presentations were categorised according to
      their diagnosis and cause for representation. Each representation was then
      classified as being avoidable or unavoidable. RESULTS: There were 10 141
      presentations to the ED during the study period, with 497 patients (4.9%, 95%
      confidence interval [CI] 4.5-5.3) representing within 72 h of discharge. Disease
      related causes of representation were seen in 55.1% (95% CI 50.7-59.5), with 39%
      (95% CI 34.8-43.4) of these caused by disease progression and 12.3% (95% CI 9.6
      15.5) for scheduled review. Patient-related causes were seen in 32.2% (95% CI
      28.2-36.4) of representations with 20.9% (95% CI 17.6-24.7) of these for patients
      who did not wait or left against medical advice. Physician-related causes were
      seen in 3.2% (95% CI 2.0-5.2) of representations. Furthermore, 23.7% (95% CI 20.2
      27.7) of patients who represented to the ED required hospital admission. A total
      of 37.0% (95% CI 32.9-41.4) of representations were assessed as being
      preventable. CONCLUSION: Early ED representations are a common problem. The
      majority of preventable representations are patient related, and interventions to
      target these areas might be of benefit in reducing this problem.

PMID- 23560965
TI  - Blind prescribing: a study of junior doctors' prescribing preparedness in an
      Australian emergency department.
AB  - OBJECTIVES: The present study examined junior residents' and registrars'
      preparedness to prescribe in an Australian ED. It measured the medication
      knowledge of participants and identified antecedent factors relevant to
      prescribing practice. METHODS: This is a prospective, exploratory study of the
      prescribing practices of 40 junior doctors. Data collection consisted of a
      participant questionnaire with three parts. Part A comprised demographic
      information; Part B comprised questions regarding prescribing practices; and Part
      C was an objective assessment of the doctor's knowledge of the most recently and
      most commonly prescribed medications. RESULTS: One hundred percent (n = 40) of
      doctors in the study had inadequate knowledge about at least one medication when
      an accuracy threshold of <80% correct was used. Seventy percent (n = 28) of the
      participants had inadequate knowledge of at least one medication when the lower
      accuracy threshold of <50% correct was used. Comparisons between medication
      knowledge score and Likert confidence scales showed that even though a doctor
      reported being completely sure about an individual medication, they most commonly
      only answered between four and six of the eight questions correctly for that
      medication. Their use of reference materials was also lacking in relation to
      their knowledge and level of confidence. The reported reasons for this included
      instructions by senior staff and time constraints. CONCLUSIONS: The majority of
      participants in the study had inadequate knowledge on medications they had most
      recently prescribed and medications most commonly prescribed in the ED. Junior
      doctors' perceptions of their medication knowledge were inflated in relation to
      their actual knowledge.

PMID- 23560966
TI  - Caught in the middle: tensions around the emergency department care of people
      with advanced cancer.
AB  - BACKGROUND: People with advanced cancer frequently present to hospital EDs.
      International studies report conflicting attitudes towards providing such care
      and difficulties with communication. The experience of Australian clinicians,
      however, is not described. OBJECTIVE: The present study aims to identify issues
      important to emergency, palliative care (PC) and oncology clinical staff in
      managing people with advanced cancer presenting to EDs. METHODS: We qualitatively
      explored views of Australian clinicians working in emergency medicine, PC and
      oncology, via focus groups at two major hospitals and two community PC services
      in Melbourne, Victoria, and emergency clinicians from all other Australian states
      and territories via semi-structured telephone interviews. Purposive sampling for
      both groups ensured representation of experience, discipline and region of work.
      The focus groups and interviews were audio-recorded, transcribed and a thematic
      analysis identified issues important to participants. RESULTS: The overarching
      theme was EDs being 'caught in the middle' when providing care to patients with
      advanced cancer in the physical environment (privacy, noise, lack of information
      and delay and lack of defined pathways), the available resources (access block
      and overcrowding, time pressures, competition with other emergencies, lack of
      alternatives) and the roles and expectations of the staff providing care
      (seniority and comfort with dying, views of dying in the ED, expertise and
      comfort in caring for those with advanced illness). CONCLUSION: Despite
      limitations in the ED environment and resources, clinicians in oncology, PC and
      emergency medicine support the important role the ED plays in providing the
      necessary access and expertise for people with advanced cancer.

PMID- 23560968
TI  - 'Registrar in charge shifts': learning how to run a busy emergency department.
AB  - OBJECTIVES: In Australasia, emergency registrars usually gain experience
      'running' an ED overnight - without supervision. This paper describes the
      introduction of FACEM-supervised daytime 'registrar in charge' (RIC) shifts into
      a tertiary adult ED over a 6 month period. METHODS: Each registrar was allocated
      at least one RIC shift during their 13 week ED term. Structured questionnaires
      gathered data regarding the educational impact of the shifts, any adverse effects
      on departmental function, changes to work practices, and perceptions of teaching
      and learning. Data were analysed using thematic analysis. RESULTS: During the
      study period, 16 senior ED registrars were rostered for 26 RIC shifts.
      Questionnaires were completed by 16/16 registrars and 13/16 emergency physicians.
      The RIC shifts were viewed positively by the emergency registrars - 93% reported
      useful feedback, felt that the shifts provided a good insight into their
      workplace behaviour, and that they should be rolled out across other departments.
      FACEMs were also positive in their evaluation, and reported little negative
      impact on departmental function. Major themes identified by both registrars and
      emergency physicians included communication skills, knowledge and experience,
      delegation, professionalism and organisational skills. Additional themes that
      were more prominent in FACEM responses included multitasking, dealing with
      interruptions, managing patient flow and being aware of the whole department.
      CONCLUSIONS: RIC shifts are a feasible and acceptable method to teach running the
      floor in the ED. Further study should assess impact on patient outcomes.

PMID- 23560967
TI  - Sub-dissociative dose intranasal ketamine for limb injury pain in children in the
      emergency department: a pilot study.
AB  - OBJECTIVE: The present study aims to conduct a pilot study examining the
      effectiveness of intranasal (IN) ketamine as an analgesic for children in the ED.
      METHODS: The present study used an observational study on a convenience sample of
      paediatric ED patients aged 3-13 years, with moderate to severe (>=6/10) pain
      from isolated limb injury. IN ketamine was administered at enrolment, with a
      supplementary dose after 15 min, if required. Primary outcome was change in
      median pain rating at 30 min. Secondary outcomes included change in median pain
      rating at 60 min, patient/parent satisfaction, need for additional analgesia and
      adverse events being reported. RESULTS: For the 28 children included in the
      primary analysis, median age was 9 years (interquartile range [IQR] 6-10). Twenty
      three (82.1%) were male. Eighteen (64%) received only one dose of IN ketamine
      (mean dose 0.84 mg/kg), whereas 10 (36%) required a second dose at 15 min (mean
      for second dose 0.54 mg/kg). The total mean dose for all patients was 1.0 mg/kg
      (95% CI: 0.92-1.14). The median pain rating decreased from 74.5 mm (IQR 60-85) to
      30 mm (IQR 12-51.5) at 30 min (P < 0.001, Mann-Whitney). For the 24 children who
      contributed data at 60 min, the median pain rating was 25 mm (IQR 4-44). Twenty
      (83%) subjects were satisfied with their analgesia. Eight (33%) were given
      additional opioid analgesia and the 28 reported adverse events were all transient
      and mild. CONCLUSIONS: In this population, an average dose of 1.0 mg/kg IN
      ketamine provided adequate analgesia by 30 min for most patients.

PMID- 23560971
TI  - Crossing the boundary: from carer to patient in one's own department.

PMID- 23560970
TI  - Whole-body computed tomography in the initial assessment of trauma patients: is
      there optimal criteria for patient selection?
AB  - OBJECTIVE: To describe the use of whole-body computed tomography (WBCT) at this
      Major Trauma Centre; to determine independent predictors of multi-region injury;
      and to evaluate the accuracy of the decision to perform WBCT in detecting multi
      region injury. METHODS: A prospective cohort study was performed at a single
      Major Trauma Centre in New South Wales, Australia. All adult patients who
      triggered trauma team activation and required an initial CT scan were studied.
      Primary outcome was the presence of multi-region injury. Logistic regression with
      stepwise selection was used to derive a prediction model for the need for WBCT
      based on our primary outcome. Receiver operator characteristic (ROC) analysis was
      used to compare the accuracy of the derived model and the clinical decision to
      perform WBCT. RESULTS: Six hundred and sixty patients were studied. WBCT scanning
      rate was 9.3% of all trauma activations. Of the patients who underwent WBCT,
      31/98 (32.0%) had multi-region injury compared with 31/562 (5.5%) who underwent
      selective CT scanning (P < 0.001). Predictors of multi-region injuries were GCS
      <9 (OR 3.0, 95% CI 1.3-7.0, P = 0.01), full trauma activation (OR 2.9, 95% CI 1.5
      5.3, P = 0.001), fall >5 m (OR 4.8, 95% CI 1.8-13.4, P = 0.003) and pedal cyclist
      (OR 3.0, 95% CI 1.2-7.5, P = 0.02). Area under ROC curve for the clinical
      decision to perform WBCT was 0.70 (95% CI 0.63-0.76) compared with 0.74 (95% CI
      0.67-0.80) for the prediction model. CONCLUSION: The decision to perform WBCT
      scans in trauma should be at the discretion of the treating clinician. Applying a
      prediction rule would increase the number of WBCT scans performed without
      improving overall accuracy.

PMID- 23560969
TI  - Feasibility and outcomes of screening for cardiovascular risk factors in the
      emergency department.
AB  - OBJECTIVES: The present study aimed to determine the prevalence of undiagnosed
      and undertreated hypercholesterolaemia and hypertension (HT) among ED patients
      and to evaluate the effects of a formal referral back to the general practitioner
      (GP) for further management. METHODS: This was a cross-sectional study of ED
      patients with follow up, if indicated. Patients aged >=35 years, without
      substantial illness or communication difficulties, were enrolled. Data were
      collected using a researcher-administered questionnaire, a point-of-care
      Accutrend(r) Plus System machine (Roche Diagnostic Australia Pty Ltd, Castle
      Hill, NSW, Australia) and digital sphygmomanometer. Patients with total
      cholesterol (TC) >=6.0 mmol/L and/or BP >=140/90 were given a referral letter and
      advised to consult their GP. The investigators made follow-up telephone calls 5
      weeks later. RESULTS: Of 827 presentations, 534 patients were enrolled (mean age
      56.7 +/- 13.3 years, 300 [56.2%] male). One hundred and eleven patients (20.7%,
      95% CI 17.5-24.5) had TC >=6.0 mmol/L. Patients with/without elevated TC differed
      significantly (P < 0.05) in regard to age, gender, GP ownership and attendance,
      and previous screening. Sixty-six patients consulted with their GP. Thirty had
      their TC levels retested, 18 received dietary/lifestyle advice and four had lipid
      lowering medication prescribed or adjusted. Ninety-six patients (18.0%, 95% CI
      14.9-21.6) had HT. Whereas 53 consulted their GP, no action was taken in 43
      cases. Investigations were ordered for three and nine had antihypertensive
      medication prescribed or adjusted. CONCLUSION: Substantial proportions of ED
      patients have undiagnosed and undertreated hypercholesterolaemia and/or HT. GP
      referral initiated interventions for many patients with hypercholesterolaemia,
      but fewer with HT. The ED has potential as a useful venue for the opportunistic
      screening of hypercholesterolaemia.

PMID- 23560973
TI  - Stroke thrombolysis: leaving the past, understanding the present and moving
      forward ....

PMID- 23560974
TI  - Response from Prof. Fatovich to Stroke thrombolysis: Leaving the past,
      understanding the present and moving forward ....

PMID- 23560975
TI  - Response from Drs Hoffman and Cooper to Stroke thrombolysis: Leaving the past,
      understanding the present and moving forward ....

PMID- 23560976
TI  - Trends in benzodiazepine abuse: 2007-2011.

PMID- 23560977
TI  - Chronically elevated high-sensitivity troponin T in obstructive sleep apnoea.

PMID- 23560978
TI  - Unilaterally impacted maxillary central incisor and canine with ipsilateral
      transposed canine-lateral incisor.
AB  - Concurrent impaction and transposition of maxillary anterior teeth is uncommon
      and poses a challenge for dentists. Early diagnosis and management of eruption
      disturbances benefits esthetic and functional outcomes. This article describes
      the treatment of a teenager who had impactions of the left maxillary central
      incisor and canine as well as ipsilateral canine-lateral incisor transposition.
      Treatment alternatives and effective orthodontic techniques are delineated. To
      optimize the treatment results, the impacted maxillary canine was surgically
      exposed and orthodontically distalized with an innovative cantilever.
      Subsequently, the deeply impacted maxillary central incisor was uncovered and
      orthodontically mesialized into the arch. Finally, the displaced maxillary
      lateral incisor was brought into its normal position. The combined surgical
      orthodontic approach resolved a difficult clinical issue and avoided additional
      restorations. An esthetic, functional outcome was achieved and satisfied the
      patient.

PMID- 23560979
TI  - Comparing simulations of lipid bilayers to scattering data: the GROMOS 43A1-S3
      force field.
AB  - Simulations of DOPC at T = 303 K were performed using the united atom force field
      43A1-S3 at six fixed projected areas, A(P) = 62, 64, 66, 68, 70, and 72 A(2), as
      well as a tensionless simulation that produced an average A(NPT) = 65.8 A(2).
      After a small undulation correction for the system size consisting of 288 lipids,
      results were compared to experimental data. The best, and excellent, fit to
      neutron scattering data occurs at an interpolated A(N) = 66.6 A(2) and the best,
      but not as good, fit to the more extensive X-ray scattering data occurs at A(X) =
      68.7 A(2). The distance DeltaDB-H between the Gibbs dividing surface for water
      and the peak in the electron density profile agrees with scattering experiments.
      The calculated area compressibility K(A) = 277 +/- 10 mN/m is in excellent
      agreement with the micromechanical experiment. The volume per lipid V(L) is
      smaller than volume experiments which suggests a workaround that raises all the
      areas by about 1.5%. Although A(X) ? A(N) ? A(NPT), this force field obtains
      acceptable agreement with experiment for A(L) = 67.5 A(2) (68.5 A(2) in the
      workaround), which we suggest is a better DOPC result from 43A1-S3 simulations
      than its value from the tensionless NPT simulation. However, nonsimulation
      modeling obtains better simultaneous fits to both kinds of scattering data, which
      suggests that the force fields can still be improved.

PMID- 23560980
TI  - Active application of liquid etching agent improves adhesion of fibre posts to
      intraradicular dentine.
AB  - AIM: To assess the effectiveness of an active application of liquid etching,
      compared with the standard gel formulation on smear layer removal from post space
      walls and push-out bond strength of luted fibre posts. METHODOLOGY: Human
      extracted teeth were collected and root filled. After post space preparation and
      cleaning with 10% ethylenediaminetetraacetic acid for 30 s, teeth were assigned
      to four groups (n = 11) according to etching procedure: (i) 37% phosphoric acid
      (H3 PO4 ) gel; (ii) 37% H3 PO4 liquid applied with an endodontic needle; (iii)
      37% H3 PO4 liquid applied with an Endovac; (iv) no etching procedure (control
      group). Three teeth per group were sectioned longitudinally and prepared for SEM
      examination to evaluate the presence of smear layer, debris, sealer/gutta-percha
      remnants, and the number of open tubules. Eight teeth per group were bonded with
      an etch-and-rinse adhesive, and fibre posts were luted with a resin-based cement.
      After cutting, specimens were prepared for a push-out test. Data were analysed by
      anova and post hoc tests (P < 0.05). RESULTS: Improved smear layer removal was
      obtained in Group 2, followed by Group 1, Group 3, and the control group (P <
      0.05). The mean values for the bond strength of the push-out test were: Group 1,
      8.3 +/- 2.9 MPa (coronal); 7.7 +/- 3.0 (middle); 3.3 +/-1.9 MPa (apical); Group
      2, 7.8 +/- 2.1 MPa (coronal); 6.9 +/- 3.9 MPa (middle); 3.7 +/- 1.3 MPa (apical);
      Group 3, 9.7 +/- 2.8 MPa (coronal); 8.6 +/- 2.1 MPa (middle); 6.9 +/- 2.3 MPa
      (apical); and Group 4, 2.9 +/- 3.0 MPa (coronal); 2.6 +/- 2.0 MPa (middle); 1.1
      +/- 2.0 MPa (apical). CONCLUSIONS: Liquid phosphoric acid applied with an
      endodontic needle yielded better canal wall smear layer removal and higher bond
      strength values when an etch-and-rinse system was used.

PMID- 23560981
TI  - Comparison of polystyrene nanoparticles and UV-inactivated antigen-displaying
      adenovirus for vaccine delivery in mice.
AB  - BACKGROUND: Inert nanoparticles are attracting attention as carriers for protein
      based vaccines. Here we evaluate the immunogenicity of the model antigen
      ovalbumin delivered on polystyrene particles and directly compare particulate
      delivery with adenovirus-based immunization. FINDINGS: Mice were vaccinated with
      soluble ovalbumin, ovalbumin-coated polystyrene particles of different sizes, or
      an adenovirus-based expression-display vector that encodes and displays a pIX
      ovalbumin fusion protein. Antibody responses were clearly higher when ovalbumin
      was administered on polystyrene particles compared to soluble protein
      administration, regardless of the particle size. Compared to adenovirus-based
      immunization, antibody levels were lower if an equivalent amount of protein was
      delivered, and no cellular immune response was detectable. CONCLUSIONS: We
      demonstrate in a side-by-side comparison that inert nanoparticles allow for the
      reduction of the administered antigen amount compared to immunization with
      soluble protein and induce strongly enhanced antibody responses, but responses
      are lower compared to adenovirus-based immunization.

PMID- 23560982
TI  - Array CGH as a first line diagnostic test in place of karyotyping for postnatal
      referrals - results from four years' clinical application for over 8,700
      patients.
AB  - BACKGROUND: Array CGH is widely used in cytogenetics centres for postnatal
      constitutional genome analysis, and is now recommended as a first line test in
      place of G-banded chromosome analysis. At our centre, first line testing by
      oligonucleotide array CGH for all constitutional referrals for genome imbalance
      has been in place since June 2008, using a patient vs patient hybridisation
      strategy to minimise costs. FINDINGS: Out of a total of 13,412 patients tested
      with array CGH, 8,794 (66%) had array CGH as the first line test. Referral
      indications for this first line group ranged from neonatal congenital anomalies
      through to adult neurodisabilities; 25% of these patients had CNVs either in
      known pathogenic regions or in other regions where imbalances have not been
      reported in the normal population. Of these CNVs, 46% were deletions or
      nullisomy, 53% were duplications or triplications, and mosaic imbalances made up
      the remainder; 87% were <5Mb and would likely not be detected by G-banded
      chromosome analysis. For cases with completed inheritance studies, 20% of
      imbalances were de novo. CONCLUSIONS: Array CGH is a robust and cost-effective
      alternative to traditional cytogenetic methodology; it provides a higher
      diagnostic detection rate than G-banded chromosome analysis, and adds to the sum
      of information and understanding of the role of genomic imbalance in disease. Use
      of novel hybridisation strategies can reduce costs, allowing more widespread
      testing.

PMID- 23560983
TI  - Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine
      guanylylation.
AB  - RtcB is an atypical RNA ligase that joins either 2',3'-cyclic phosphate or 3'
      phosphate termini to 5'-hydroxyl termini. In contrast to typical RNA ligases,
      which rely on ATP and Mg(II), catalysis by RtcB is dependent on GTP and Mn(II)
      with ligation proceeding through a covalent RtcB-histidine-GMP intermediate.
      Here, we present three structures of Pyrococcus horikoshii RtcB complexes that
      capture snapshots along the entire guanylylation pathway. These structures show
      that prior to binding GTP, a single manganese ion (Mn1) is bound to RtcB. To
      capture the step immediately preceding RtcB guanylylation, we determined a
      structure of RtcB in complex with Mn(II) and the unreactive GTP analogue
      guanosine 5'-(alpha-thio)triphosphate (GTPalphaS). This structure shows that Mn1
      is poised to stabilize the pentavalent transition state of guanylylation while a
      second manganese ion (Mn2) is coordinated to a nonbridging oxygen of the gamma
      phosphoryl group. The pyrophosphate leaving group of GTPalphaS is oriented
      apically to His404 with the epsilon-nitrogen poised for in-line attack on the
      alpha-phosphorus atom. The structure of RtcB in complex with GTPalphaS also
      reveals the network of hydrogen bonds that recognize GTP and illuminates the
      significant conformational changes that accompany the binding of this cofactor.
      Finally, a structure of the enzymic histidine-GMP intermediate depicts the end of
      the guanylylation pathway. The ensuing molecular description of the RtcB
      guanylylation pathway shows that RtcB and classical ATP- and Mg(II)-dependent
      nucleic acid ligases have converged upon a similar two-metal mechanism for
      formation of the nucleotidylated enzyme intermediate.

PMID- 23560985
TI  - Dual-colour multiplex staining for p40 and CK 5/6 in cytology samples for non
      small cell lung cancer: a powerful combination for minimalist immunocytochemistry
      analysis.

PMID- 23560984
TI  - Genetic regulation of glucoraphanin accumulation in Beneforte broccoli.
AB  - . Diets rich in broccoli (Brassica oleracea var italica) have been associated
      with maintenance of cardiovascular health and reduction in risk of cancer. These
      health benefits have been attributed to glucoraphanin that specifically
      accumulates in broccoli. The development of broccoli with enhanced concentrations
      of glucoraphanin may deliver greater health benefits. . Three high-glucoraphanin
      F1 broccoli hybrids were developed in independent programmes through genome
      introgression from the wild species Brassica villosa. Glucoraphanin and other
      metabolites were quantified in experimental field trials. Global SNP analyses
      quantified the differential extent of B. villosa introgression . The high
      glucoraphanin broccoli hybrids contained 2.5-3 times the glucoraphanin content of
      standard hybrids due to enhanced sulphate assimilation and modifications in
      sulphur partitioning between sulphur-containing metabolites. All of the high
      glucoraphanin hybrids possessed an introgressed B. villosa segment which
      contained a B. villosa Myb28 allele. Myb28 expression was increased in all of the
      high-glucoraphanin hybrids. Two high-glucoraphanin hybrids have been
      commercialised as Beneforte broccoli. . The study illustrates the translation of
      research on glucosinolate genetics from Arabidopsis to broccoli, the use of wild
      Brassica species to develop cultivars with potential consumer benefits, and the
      development of cultivars with contrasting concentrations of glucoraphanin for use
      in blinded human intervention studies.

PMID- 23560986
TI  - The all-on-four treatment concept: a systematic review.
AB  - PURPOSE: The study aims to evaluate the all-on-four treatment concept with regard
      to survival rates (SRs) of oral implants, applied fixed dental prostheses (FDPs)
      and temporal changes in proximal bone levels. MATERIALS AND METHODS: A systematic
      review of publications in English and German was performed using the electronic
      bibliographic database MEDLINE, the Cochrane Library, and Google. Hand searches
      were conducted of the bibliographies of related journals and systematic reviews.
      The authors performed evaluations of articles independently, as well as data
      extraction and quality assessment. Data were submitted the weighted least-squared
      analysis. RESULTS: Thirteen (487 initially identified) papers met inclusion
      criteria. A number of 4,804 implants were initially placed, of which 74 failed,
      with a majority of failures (74%) within the first 12 months. A total of 1,201
      prostheses were incorporated within 48 hours after the surgery. The major
      prosthetic complication was the fracture of the all-acrylic FDP. The mean
      cumulative SR/SR +/- (standard deviation) (36 months) of implants and prostheses
      were 99.0 +/- 1.0% and 99.9 +/- 0.3%, respectively. The averaged bone loss was
      1.3 +/- 0.4 mm (36 months). No statistically significant differences were found
      in outcome measures, when comparing maxillary versus mandibular arches and
      axially versus tilted placed implants. CONCLUSION: The available data provide
      promising short-term results for the all-on-four treatment approach; however,
      current evidence is limited by the quality of available studies and the paucity
      of data on long-term clinical outcomes of 5 years or greater. In terms of an
      evidence-based dentistry, the authors recommend further studies designed as
      randomized controlled clinical trials and reported according to the CONSORT
      statement.

PMID- 23560987
TI  - Energy technologies evaluated against climate targets using a cost and carbon
      trade-off curve.
AB  - Over the next few decades, severe cuts in emissions from energy will be required
      to meet global climate-change mitigation goals. These emission reductions imply a
      major shift toward low-carbon energy technologies, and the economic cost and
      technical feasibility of mitigation are therefore highly dependent upon the
      future performance of energy technologies. However, existing models do not
      readily translate into quantitative targets against which we can judge the
      dynamic performance of technologies. Here, we present a simple, new model for
      evaluating energy-supply technologies and their improvement trajectories against
      climate-change mitigation goals. We define a target for technology performance in
      terms of the carbon intensity of energy, consistent with emission reduction
      goals, and show how the target depends upon energy demand levels. Because the
      cost of energy determines the level of adoption, we then compare supply
      technologies to one another and to this target based on their position on a cost
      and carbon trade-off curve and how the position changes over time. Applying the
      model to U.S. electricity, we show that the target for carbon intensity will
      approach zero by midcentury for commonly cited emission reduction goals, even
      under a high demand-side efficiency scenario. For Chinese electricity, the carbon
      intensity target is relaxed and less certain because of lesser emission
      reductions and greater variability in energy demand projections. Examining a
      century-long database on changes in the cost-carbon space, we find that the
      magnitude of changes in cost and carbon intensity that are required to meet
      future performance targets is not unprecedented, providing some evidence that
      these targets are within engineering reach. The cost and carbon trade-off curve
      can be used to evaluate the dynamic performance of existing and new technologies
      against climate-change mitigation goals.

PMID- 23560988
TI  - Clinical characteristics of collagenous colitis with linear ulcerations.
AB  - BACKGROUND: The relationship between the thickness of subepithelial collagen
      bands (CB) and the development of linear ulcerations (LU) in collagenous colitis
      (CC) remains unclear. The aim of the present study was to compare the clinical
      and pathological features, including the thickness of CB, in CC patients with and
      without LU. PATIENTS AND METHODS: Twenty-five patients with CC diagnosed by
      pathological examination of biopsy specimens were analyzed. Eleven patients with
      LU (LU group) and 14 patients without LU (non-LU group) were compared. RESULTS:
      Ten patients in the LU group and seven in the non-LU group were taking
      lansoprazole (P = 0.038). Seven patients in the LU group and one in the non-LU
      group were taking non-steroidal anti-inflammatory drugs (NSAIDs) (P = 0.004). All
      LU were locatedin the transverse or left colon. Patients in the LU group were
      older than those in the non-LU group (P = 0.015). CB were significantly thicker
      in the LU group than in the non-LU group (mean +/- SD, 40 +/- 21 MUm vs 20 +/- 11
      MUm, P = 0.004). Multivariate analysis showed that NSAIDs use (odds ratio,
      19.236; 95% confidence interval, 1.341-275.869) and CB thickness (odds ratio,
      0.893; 95% confidence interval, 0.804-0.999) were independently associated with
      the development of LU. CONCLUSION: Use of lansoprazole and NSAIDs, thick CB, and
      advanced age are associated with the development of LU in CC patients.

PMID- 23560989
TI  - Star polymers with a cationic core prepared by ATRP for cellular nucleic acids
      delivery.
AB  - Poly(ethylene glycol) (PEG)-based star polymers with a cationic core were
      prepared by atom transfer radical polymerization (ATRP) for in vitro nucleic acid
      (NA) delivery. The star polymers were synthesized by ATRP of 2
      (dimethylamino)ethyl methacrylate (DMAEMA) and ethylene glycol dimethacrylate
      (EGDMA). Star polymers were characterized by gel permeation chromatography, zeta
      potential, and dynamic light scattering. These star polymers were combined with
      either plasmid DNA (pDNA) or short interfering RNA (siRNA) duplexes to form
      polyplexes for intracellular delivery. These polyplexes with either siRNA or pDNA
      were highly effective in NA delivery, particularly at relatively low star polymer
      weight or molar ratios, highlighting the importance of NA release in efficient
      delivery systems.

PMID- 23560990
TI  - Alpha-1 antitrypsin augmentation therapy and biomarkers of elastin degradation.
AB  - BACKGROUND: Intravenous alpha-1 antitrypsin protein (AAT) augmentation is a
      prescribed therapy for severe, genetically determined, alpha-1 antitrypsin
      deficiency (AATD), a genetic basis for pulmonary emphysema. AAT, a predominant
      systemic inhibitor of neutrophil elastase thus far has not been shown to decrease
      elastin degradation in a significant number of patients on this therapy. The
      objective of this study was to compare levels of biomarkers of elastin
      degradation in plasma, bronchoalveolar lavage (BALF) fluid and urine before and
      after beginning AAT augmentation therapy in patients with AATD. METHODS:
      Desmosine and isodesmosine (DI), which occur only in elastin, are amino acid
      cross-links in mature elastin. Levels of DI in body fluids measure degradation of
      elastin and can be measured more specifically by mass spectrometry. This method
      was used to measure DI levels in plasma, bronchoalveolar lavage fluid and urine
      in cohorts of severe AATD patients on augmentation, not on augmentation and
      before and after the initiation of augmentation therapy. RESULTS: Statistically
      significant reductions in plasma DI and in BALF DI were demonstrated in AATD
      patients receiving intravenous (IV) augmentation therapy as compared with those
      not receiving it. Administration by aerosol also produced statistically
      significant reductions in levels of DI in BALF. CONCLUSIONS: Results indicate
      that the currently prescribed doses of AAT augmentation inhibit neutrophil
      elastase adequately to reduce elastin degradation, both systemically and in the
      lung per se. The currently prescribed doses did not reduce elastin degradation to
      control levels, which may be possible with higher doses.

PMID- 23560991
TI  - The prevalence of anisometropia and its associated factors in an adult population
      from Shahroud, Iran.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence of anisometropia
      in an urban adult population in the north of Iran. METHODS: This cross-sectional
      study was conducted among the 40-64-year-old population in Shahroud, Iran. Random
      cluster sampling was applied to select 6,311 people. Following an interview,
      optometric and ophthalmologic examinations, including objective non-cycloplegic
      refractions, were carried out. The prevalence of anisometropia was reported
      according to non-cycloplegic refraction and with cut-off points of 0.50, 1.00,
      2.00 and 3.00 D. RESULTS: Of the sampled people, 5,190 (82.2 per cent) took part
      in the study. After considering exclusion criteria, data from 4,918 participants
      were included in the final analysis. Most participants were female (57.6 per
      cent) and the average age (with standard deviation) was 50.7 +/- 6.2 years. The
      prevalence of anisometropia with cut-off points of 0.50, 1.00 and 2.00 D were
      23.1 (95%CI: 22.0-24.3), 7.7 (95%CI: 7.0-8.4) and 3.2 per cent (95%CI: 2.7-3.7),
      respectively. The prevalence of severe anisometropia (3.00 D or more) was 1.9 per
      cent (95%CI: 1.5-2.3). The odds ratio (OR) of anisometropia was 1.06 times higher
      for every year of increasing age. The OR of anisometropia in participants with
      cataract was 2.78 times more than in those without (p < 0.001). Anisometropia was
      more frequent among participants with unilateral cataract (21.7 per cent)
      compared to those with bilateral cataract (13.4 per cent). Anisometropia of 1.00
      D or more was significantly more prevalent among myopic participants compared to
      hyperopic participants (13.8 versus 12.7 per cent, p < 0.001) and there was a
      stronger association between anisometropia and myopia (OR = 2.93) than hyperopia
      (OR = 2.23). With increasing educational level, the prevalence of anisometropia
      decreased significantly (p < 0.001). The prevalence of aniso-astigmatism of 1.00
      D or more was 11.1 per cent (95%CI: 10.2-11.9). CONCLUSION: In the present study,
      the prevalence of anisometropia in Iran was not negligible; however, it is less
      than in Eastern Asia. Myopia, cataract, age and educational level were associated
      with anisometropia.

PMID- 23560992
TI  - Gabexate mesylate as treatment in the course of ANCA-negative microscopic
      polyangiitis.
AB  - Patients with small vessel vasculitis present fluctuating antineutrophil
      cytoplasmic antibodies (ANCA) levels to the point that positive ANCA may be
      missed even if only up to 10% of patients with microscopic polyangiitis (MPA) are
      ANCA-negative. The first-line treatment of MPA is the association of steroids and
      cyclophosphamide, especially in the presence of a rapidly progressive
      glomerulonephritis. Plasmapheresis, intravenous immunoglobulins, and tumor
      necrosis factor inhibitors have been proposed as alternative to standard therapy.
      Disseminated intravascular coagulation (DIC) is a possible event in the course of
      small vessel vasculitis. Gabexate mesylate is a protease inhibitor able to
      suppress endothelial cell injury, and it may be administered to treat DIC related
      to different diseases. In ANCA-associated vasculitis, cytokines play a key role
      in promoting endothelial damage. DIC-related thrombocytopenia may be
      misinterpreted as drug-induced because of the immunosuppressive properties of
      cyclophosphamide. Two cases of ANCA-positive MPA associated with DIC and treated
      with gabexate are reported in the literature with improvement of both
      hematological disorder and renal function. Our patient presented a rapidly
      progressive glomerulonephritis, and the renal biopsy showed MPA, in the absence
      of ANCA. After two weeks of steroid treatment, our patient developed a DIC. This
      case represents the first report of ANCA-negative MPA managed with gabexate,
      which showed improvement of coagulation disorders and kidney function. In
      conclusion, the anti-inflammatory properties of gabexate could be helpful in MPA
      at increased bleeding risk when immunosuppressive treatment is contraindicated,
      even in ANCA-negative vasculitis.

PMID- 23560993
TI  - The role of prohepcidin in anemia due to Helicobacter pylori infection.
AB  - BACKGROUND: Hepcidin, a key regulator of iron homeostasis, increases when
      inflammation and some infections occur. It plays a critical role in macrophage
      iron retention, which underlies inflammation/infection caused anemia. It is known
      that Helicobacter pylori (HP) may lead to iron deficiency (ID) due to occult
      blood loss or reduced iron absorption. This study investigates the role of
      prohepcidin, hepcidin's precursor, in ID and ID anemia (IDA) with a concurrent HP
      infection. METHODS: In this prospectively designed study, 15 patients with IDA
      and a concurrent HP infection (group 1), 11 patients with an ID and a concurrent
      HP infection (group 2), and 18 patients with HP infection (group 3) were
      observed. All groups received only HP eradication therapy. Twenty-five age- and
      sex-matched children without ID/IDA and HP infection were included in the study
      as the control group. In all groups and control group, measurements were taken
      for pre- and posttreatment hemoglobin, serum prohepcidin, serum ferritin, serum
      iron (SI), transferrin saturation, erythrocyte sedimentation rate, fibrinogen,
      and C-reactive protein levels. RESULTS: The pretreatment prohepcidin levels were
      significantly higher only in group 1 compared to the control group (P < .05). In
      group 1, a significant increase in hemoglobin and SI levels and a significant
      reduction in prohepcidin levels were additionally observed following HP
      eradication treatment (P < .05). However, in groups 2 and 3, significant
      differences in hemoglobin, iron, and prohepcidin levels between pre- and
      posttreatment were not observed. CONCLUSION: Elevated serum prohepcidin might
      indicate the role of inflammation in the etiology of anemia concurrent with HP.

PMID- 23560994
TI  - Enzymatic properties of beta-1,3-glucanase from Streptomyces sp Mo.
AB  - Streptomyces sp Mo endo-beta-1,3-glucanase was found to have hydrolyzing activity
      toward curdlan and released laminarioligosaccharides selectively. The molecular
      weight was estimated to be 36000 Da and its N-terminal amino acid sequence was
      VTPPDISVTN. The optimal pH was 6 and the enzyme was found to be stable from pH 5
      to 8. The optimal temperature was 60  degrees C and the activity was stable below
      50  degrees C. The enzyme hydrolyzed selectively curdlan containing only beta-1,3
      linkages. The enzyme had 89% relative activity toward Laminaria digitata
      laminarin, which contains a small amount of beta-1,6 linkages compared with
      curdlan, while Eisenia bicyclis laminarin with a higher amount of beta-1,6
      linkages, was not hydrolyzed. Mo enzyme adsorbed completely on curdlan powder.
      The enzymatic hydrolysis of curdlan powder resulted in the accumulation of
      laminaribiose (yield 81.7%). Trisaccharide was inevitably released from the
      hydrolysis of laminarioligosaccharides with 5 to 7 degrees of polymerization
      (DP). Although the enzyme cleaved off disaccharide (DP 2) from tetrasaccharide
      (DP 4), the reaction rate was lower than those of DP 5 to 7. The results
      indicated that the active site of Mo endo-beta-1,3-glucanase can efficiently
      recognize glucosyl residue chain of greater than DP 5 and hydrolyzes the beta-1,3
      linkage between the 3rd and 4th glucosyl residue.

PMID- 23560996
TI  - When potatoes fly.

PMID- 23560997
TI  - Comparison of mathematical models of lactic acid bacteria growth in vacuum
      packaged raw beef stored at different temperatures.
AB  - The lactic acid bacteria grown in vacuum-packaged raw beef under 7, 10, 15, and
      20  degrees C has been studied in this paper. Four primary models, the modified
      Gompertz, logistic, Baranyi, and Huang model were used for data fitting.
      Statistical criteria such as the bias factor and accuracy factor, mean square
      error, Akaike's information criterion, and the residual distribution were used
      for comparing the models. The result showed that all of the 4 models can fit the
      data well and they were not significantly different in the performance. They were
      equally capable of describing bacterial growth, but the growth rate and lag time
      estimated from the modified Gompertz model were a little higher than other
      models. The estimate for the lag time was not accurate as the growth rate.

PMID- 23560999
TI  - Cell-free protein synthesis and substrate specificity of full-length
      endoglucanase CelJ (Cel9D-Cel44A), the largest multi-enzyme subunit of the
      Clostridium thermocellum cellulosome.
AB  - Endoglucanase CelJ (Cel9D-Cel44A) is the largest multi-enzyme subunit of the
      Clostridium thermocellum cellulosome and is composed of glycoside hydrolase (GH)
      families 9 and 44 (GH9 and GH44) and carbohydrate-binding module (CBM) families
      30 and 44 (CBM30 and CBM44). The study of CelJ has been hampered by the inability
      to isolate full-length CelJ from recombinant Escherichia coli cells. Here, full
      length CelJ and its N- and C-terminal segments, CBM30-GH9 (Cel9D) and GH44-CBM44
      (Cel44A), were synthesized using a wheat germ cell-free protein synthesis system
      and then were purified to homogeneity. Analysis of the substrate specificities of
      CelJ and its derivatives demonstrated that the fusion of Cel9D and Cel44A results
      in threefold synergy for the degradation of xyloglucan, one of the major
      structural polysaccharides of plant cell walls. Because CelJ displayed broad
      substrate specificity including significant carboxymethylcellulase (CMCase) and
      xylanase activities in addition to high xyloglucanase activity, CelJ may play an
      important role in the degradation of plant cell walls, which are composed of
      highly heterogeneous polysaccharides. Furthermore, because Cel9D, but not Cel44A,
      acts as a semi-processive endoglucanase, the different modes of action between
      Cel9D and Cel44A may be responsible for the observed synergistic effect on the
      activity of CelJ (Cel9D-Cel44A).

PMID- 23561000
TI  - Fluorescein prototropism within poly(ethylene glycol)s and their aqueous
      mixtures.
AB  - Depending on the solubilizing milieu and conditions, fluorescein may exist in one
      or more of its many prototropic forms [cationic, neutral (zwitterionic, quinoid,
      and lactone), monoanionic (phenolate and carboxylate), and dianionic].
      Fluorescein prototropism is investigated in liquid poly(ethylene glycol)s (PEGs)
      of different average molecular weight (MW) and their aqueous mixtures using UV
      vis absorbance along with static and time-resolved fluorescence spectroscopic
      techniques. Information regarding various prototropic forms of fluorescein in up
      to 30 wt % different average MW PEG-added aqueous buffers at varying pH reveals
      that addition of PEG causes lactonization of fluorescein in the milieu; higher
      the average MW of PEG, the more the lactonization is. Neat PEG200, PEG400, and
      PEG600 are found to support the dianionic form of fluorescein, while PEG1000
      supports the neutral lactonized form. It is demonstrated that various prototropic
      forms of fluorescein may be generated within PEGs by addition of adequate amounts
      of acidic aqueous buffer. Significant bathochromic shift in absorbance and
      fluorescence band maxima of dianionic fluorescein as concentration of PEG200 is
      increased correlates well with hydrogen bond accepting basicity, hydrogen bond
      donating acidity, and dipolarity/polarizability of the aqueous PEG200 mixture.
      Interestingly, fluorescence emission from the cationic form of fluorescein is
      observed from dilute aqueous acidic media in the presence of high concentration
      of PEG200, whereas the fluorescence emission from cation in the absence of PEG200
      is observed only from aqueous solutions of very high acidity (>5 M [H(+)]).
      Excited-state intensity decay is also used to support this outcome. It is
      proposed that, in the presence of a small amount of acid in PEG200, a highly
      acidic water-rich solvation microenvironment is formed around fluorescein, which
      converts its dianionic form to cationic form and considerably hinders the rapid
      deprotonation of the excited state of the cationic form.

PMID- 23561001
TI  - More age-care staff report helping care recipients following a brief depression
      awareness raising intervention.
AB  - BACKGROUND: Those working with elderly care recipients require a good working
      knowledge of depression and appropriate help giving responses. While it is
      important for age-care staff to recognize depression in care recipients it is
      also critical that they know the appropriate course of action to assist a care
      recipient who may be depressed. This study aims to determine the knowledge of age
      care staff of appropriate help giving responses, their confidence in knowing what
      kind of assistance to provide and their actual likelihood of providing help to
      potentially depressed care recipients and to examine if these measures improve
      following an intervention training program. METHODS: One hundred and two age-care
      staff were surveyed on their confidence in helping age-care recipients and on
      their knowledge of appropriate ways to provide assistance. Staff then
      participated in a two hour depression awareness raising intervention. The survey
      was repeated immediately following the training and again six months later.
      RESULTS: Staff confidence in knowing how to provide assistance increased
      significantly subsequent to training and remained significantly improved at the
      six month follow up. In addition, a significantly higher proportion of staff
      reported helping care recipients at the six month follow up. CONCLUSIONS: This
      study highlights the potential of a brief staff training program to provide a
      cost effective means to improve staff self-confidence and increase the likelihood
      of staff providing assistance to depressed care recipients.

PMID- 23561002
TI  - Efficacy of preoperative ibuprofen on the success of inferior alveolar nerve
      block in patients with symptomatic irreversible pulpitis: a randomized clinical
      trial.
AB  - AIM: To evaluate the effect of preoperative oral ibuprofen (IBU) on the success
      of inferior alveolar nerve blocks (IANBs) with mepivacaine containing 1 : 100 000
      epinephrine for patients with symptomatic irreversible pulpitis (SIP).
      METHODOLOGY: The present study was a double-blind, randomized, placebo-controlled
      clinical trial. The study included two study groups each consisting of 25
      patients who exhibited symptomatic irreversible pulpitis of a mandibular
      posterior tooth. The patients presented prolonged moderate or severe pain (>10 s)
      after cold testing and indicated their pain scores on a Heft-Parker visual
      analogue scale. The patients received identically appearing capsules containing
      either 600 mg IBU (IBUg) or gelatin (placebo, PLAg) 1 h before administration of
      IANB with 2% mepivacaine containing 1 : 100 000 epinephrine. After 15 min, the
      anaesthetic blockade was assessed by a three-step examination (lip numbness,
      positive/negative response to cold testing and clinical discomfort during
      endodontic access). IANB success was defined as the absence of pain during any of
      these evaluations. The data were analysed using the chi-squared test. RESULTS:
      All of the patients reported moderate or severe pain before the preoperative
      procedure. Statistically significant differences were observed between the IBUg
      and PLAg (P < 0.05); the success rates for the IANB were 72% (IBUg) and 36%
      (PLAg). CONCLUSIONS: Preoperative oral administration of IBU significantly
      improved the efficacy of IANB in patients with symptomatic irreversible pulpitis.

PMID- 23561003
TI  - Awareness regarding the importance of calcium and vitamin D among the
      undergraduate pharmacy students in Bangladesh.
AB  - BACKGROUND: Calcium and vitamin D are two important micronutrients required for
      maintaining proper bone health. Previous works intended to determine the status
      of these micronutrients in local population have reported that the people in
      Bangladesh are at high risk of calcium insufficiency and hypovitaminosis D
      related health complications. Lack of awareness and insufficient knowledge of the
      essentiality of these two nutrients are assumed to cause this problem in
      Bangladesh. The present study was designed and conducted to establish a basic
      understanding on the level of gap of knowledge and awareness among pharmacy
      students at undergraduate level in Bangladesh. FINDINGS: A total of 713 students
      of Bachelor of Pharmacy course participated in the study. The students were asked
      about basic idea related to calcium and vitamin D and the disorders due to their
      deficiency, name of common foods containing calcium and vitamin D, their
      perception regarding the essentiality of the said nutrients etc. It was found
      that most of the students were familiar with the importance of calcium (98.9%)
      and vitamin D (99.3%) in bone health. 82.2% students know about the term
      osteoporosis. Unfortunately, 10.7% and 18.8% students failed to mention at least
      one food that is rich in calcium and vitamin D, respectively. Most of the
      students got familiar about the nutrients from their teachers (48.9%) and
      textbooks (32.8%). CONCLUSION: Being a student of pharmacy, the students should
      have more comprehensive knowledge about calcium and vitamin D. The present study
      indicates that the pharmacy students have lack of knowledge about calcium and
      vitamin D and thus it can be clearly predicted that the condition of general
      people may be worse.

PMID- 23561004
TI  - The effects of anxiety and depression symptoms on treatment adherence in COPD
      patients.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) may cause some
      psychiatric disorders such as depression and anxiety, similar to other chronic
      diseases. Treatment adherence may be affected by worsening of cognitive
      functions. We aimed to show whether the symptoms of anxiety and depression affect
      treatment adherence by patients. METHOD: Seventy-eight COPD patients were
      analysed at the first visit. The use of bronchodilator therapy was revised for
      standardization before they attended a second visit after six months. Hospital
      Anxiety and Depression Scale (HADS), Anxiety Sensitivity Index-3 (ASI-3) and SF
      36 Questionnaire were carried out at that visit. 'National Guide of Turkish
      Thoracic Society for Asthma' was used for scoring method of use of the
      bronchodilator and evaluating treatment adherence (including maintenance
      therapy). RESULTS: Sixty-two of 78 patients, 53 (85.5%) men and nine (14.5%)
      women with a mean age of 64.9 +/- 9.9 joined the second visit. Thirty-three
      patients (53.2%) had a high-treatment adherence (HTA), whereas 29 (46.8%) had a
      low-treatment adherence (LTA). There were high scores of anxiety in 18 (29%) and
      depression in 11 (17.7%) patients. There was no statistical difference between
      the HTA and LTA groups in means of age, gender, educational level, presence of
      comorbidity, classification of COPD, high anxiety scores according to HADS and
      ASI-3 scores. Of the patients, 41.4% in the LTA group were still smoking, whereas
      it was only 12.1% in the HTA group (P = 0.009). The LTA group had higher
      depression scores (P = 0.004) than the HTA group. Dyspnea was found more frequent
      in LTA patients (P = 0.047); vitality score was also statistically low in this
      group (P = 0.01). CONCLUSION: As a result, continuing smoking and the presence of
      depression symptoms may decrease adherence to treatment. Therefore, to increase
      the adherence to treatment and reduce symptoms such as dyspnea, it is important
      to treat any depressive symptoms that are present and to help patients cease
      smoking.

PMID- 23561005
TI  - Telephone consultations in place of face to face out-patient consultations for
      patients discharged from hospital following surgery: a systematic review.
AB  - BACKGROUND: Routine follow-up following uncomplicated surgery is being delivered
      by telephone in some settings. Telephone consultations may be preferable to
      patients and improve outpatient resource use. We aimed to compare the
      effectiveness of telephone consultations with face to face follow-up
      consultations, in patients discharged from hospital following surgery. METHODS:
      Seven electronic databases (including Medline, Embase and PsycINFO) were searched
      from inception to July 2011. Comparative studies of any design in which routine
      follow-up via telephone was compared with face to face consultation in patients
      discharged from hospital after surgery were included. Study selection, data
      extraction and quality appraisal were performed independently by two reviewers
      with consensus reached by discussion and involvement of a third reviewer where
      necessary. RESULTS: Five papers (four studies; 865 adults) met the inclusion
      criteria. The studies were of low methodological quality and reported dissimilar
      outcomes precluding any formal synthesis. CONCLUSIONS: There has been very little
      comparative evaluation of different methods of routine follow-up care in patients
      discharged from hospital following surgery. Further work is needed to establish a
      role for telephone consultation in this patient group.

PMID- 23561007
TI  - Graphene oxide-facilitated reduction of nitrobenzene in sulfide-containing
      aqueous solutions.
AB  - The main objective of this study was to test the possibility that graphene-based
      nanomaterials can mediate environmentally relevant abiotic redox reactions of
      organic contaminants. We investigated the effect of graphene oxide (GO) on the
      reduction of nitrobenzene by Na2S in aqueous solutions. With the presence of GO
      (typically 5 mg/L), the observed pseudofirst-order rate constant (kobs) for the
      reduction of nitrobenzene was raised by nearly 2 orders of magnitude (from 7.83 *
      10(-5) h(-1) to 7.77 * 10(-3) h(-1)), strongly suggesting reaction mediation by
      GO. As reflected by the combined spectroscopic analyses, GO was reduced in the
      beginning of the reaction, and hence the reduced GO (RGO) mediated the reduction
      of nitrobenzene. It was proposed that the zigzag edges of RGO acted as the
      catalytic active sites, while the basal plane of RGO served as the conductor for
      the electron transfer during the catalytic process. Furthermore, changing the pH
      (5.9-9.1) and the presence of dissolved humic acid (10 mg TOC/L) were found to
      greatly influence the catalytic activity of RGO. The results imply that graphene
      based nanomaterials may effectively mediate the reductive transformation of
      nitroaromatic compounds and can contribute to the natural attenuation and
      remediation of these chemicals.

PMID- 23561008
TI  - Homeopathic drug proving of Okoubaka aubrevillei: a randomised placebo-controlled
      trial.
AB  - BACKGROUND: Homeopathic drug proving is a basic concept in homeopathy. This study
      aimed to record symptoms produced by a homeopathic drug compared with placebo.
      METHODS: This multicentre, randomised, double-blind, placebo-controlled phase 1
      trial consisted of a 7-day run-in period, a 5-day intervention period and a 16
      day post-intervention observation period. Subjects, investigators and
      statisticians were blinded for intervention groups and identity of the
      homeopathic drug. Subjects in the intervention group received Okoubaka
      aubrevillei (potency C12) and subjects in the placebo group received the
      optically identical sucrose globules. Dosage in both groups was five globules
      taken five times per day over a maximum period of 5 days. Subjects documented the
      symptoms they experienced in a semistructured online diary. The primary outcome
      parameter was the number of characteristic proving symptoms compared with placebo
      after a period of 3 weeks. Characteristic symptoms were categorised using content
      analysis. Secondary outcome parameters were the qualitative differences in
      profiles of characteristic and proving symptoms and the total number of all
      proving symptoms. The number of symptoms was quantitatively analysed on an
      intention-to-treat basis using analyses of covariance with the subject's
      expectation and baseline values as covariates. RESULTS: Thirty-one subjects were
      included (19 Okoubaka and 12 placebo). Data for 29 participants could be
      analysed. No significant differences in number of characteristic symptoms in both
      groups were observed between Okoubaka (mean+/-standard deviation 5.4+/-6.0) and
      placebo (4.9+/-5.6). The odds ratio for observation of a characteristic symptom
      was 1.11 (95% confidence interval 0.4 to 3.05, P=0.843). Females and subjects
      expecting a higher number of symptoms at baseline or feeling more sensitive to
      homeopathic drugs experienced more characteristic symptoms regardless of
      allocation. The qualitative analysis showed an inter-coder reliability of 0.69
      (95% confidence interval 0.62 to 0.76). The qualitative comparison of symptom
      profiles was inconclusive. CONCLUSIONS: Combined results of qualitative and
      quantitative methods did not result in a significant difference of characteristic
      proving symptoms between O. aubrevillei C12 and placebo. The qualitative
      comparison of the symptom profiles leaves some open questions. The nocebo effect
      might be a plausible explanation for most of the phenomena observed in this
      trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01061229.

PMID- 23561009
TI  - Anomalous EPR intensity distribution of the methyl radical quartet adsorbed on
      the surface of porous materials. Comparison with solid gas matrix isolation.
AB  - The two inner lines of the EPR quartet of methyl radicals trapped in cryogenic
      gas matrices are superpositions of the inner transitions of an A-proton-spin
      quartet and an E-proton-spin doublet. Their intensity relative to the outer lines
      provides information on the population of the methyl-rotation quantum states. The
      above intensity ratio for the CH3 in solids is a challenging problem of the
      quantum dynamics and statistical thermodynamics. The influence of the quantum
      mechanical/inertial rotation on the intensity distribution of the hf components
      of methyl radical on the surface of porous materials, e.g., silica gel, is
      investigated by EPR line shape simulations and compared with spectra of the
      radical isolated in the bulk of solid gas samples. The experimental part of this
      study includes the first in literature EPR observation of methyl radical in the
      bulk of N2O solid and provides new essential information on CH3 in CO2 and Ar
      matrices, thus, covering both strongly hindered and almost free rotation of the
      radical. We verify the observation of nonrotating methyl radicals in a N2O
      matrix, discovered earlier in cold CO2, give a thorough account of their EPR
      characteristics, and explore their formation at the inner surface of porous
      materials. Combination of a classical spin-Hamiltonian with employment of quantum
      effects due to nuclear spin-rotation coupling and the radical symmetry were used
      to interpret the experimental spectral observations. The cause of experimentally
      found unexpected contribution of the excited degenerate E-doublets to the EPR
      spectrum down to 4.2 K and A/E transition amplitude ratios sometimes as high as
      ca. 1:8 at liquid-N2 temperature is sought. The validity of Bose-Einstein quantum
      (BEq-) statistics of the spin rotation states in addition to the classical
      Maxwell-Boltzmann (Boltzmann) statistics was also assessed against experimental
      population A/E-ratio data. The BEq-statistics were not previously applied to
      similar systems. Furthermore, detailed consideration of the laboratory/free space
      rotational degeneracy and the planarity of methyl radical was also included in
      this work.

PMID- 23561010
TI  - Hydrated interfacial ions and electrons.
AB  - Charged particles such as hydrated ions and transient hydrated electrons, the
      simplest anionic reducing agents in water, and the special hydronium and
      hydroxide ions at water interfaces play an important role in many fields of
      science, such as atmospheric chemistry, radiation chemistry, and biology, as well
      as biochemistry. This article focuses on these species near hydrophobic
      interfaces of water, such as the air or vacuum interface of water or water
      protein/membrane interfaces. Ions at interfaces as well as solvated electrons
      have been reviewed frequently during the past decade. Although all species have
      been known for some time with seemingly familiar features, recently the picture
      in all cases became increasingly diffuse rather than clearer. The current account
      gives a critical state-of-the art overview of what is known and what remains to
      be understood and investigated about hydrated interfacial ions and electrons.

PMID- 23561011
TI  - Accurate first principles model potentials for intermolecular interactions.
AB  - The general effective fragment potential (EFP) method provides model potentials
      for any molecule that is derived from first principles, with no empirically
      fitted parameters. The EFP method has been interfaced with most currently used ab
      initio single-reference and multireference quantum mechanics (QM) methods,
      ranging from Hartree-Fock and coupled cluster theory to multireference
      perturbation theory. The most recent innovations in the EFP model have been to
      make the computationally expensive charge transfer term much more efficient and
      to interface the general EFP dispersion and exchange repulsion interactions with
      QM methods. Following a summary of the method and its implementation in generally
      available computer programs, these most recent new developments are discussed.

PMID- 23561012
TI  - Retinal nerve fibre layer thickness and optic nerve head size measured in high
      myopes by optical coherence tomography.
AB  - BACKGROUND: The retinal nerve fibre layer (RNFL) thickness is reportedly
      decreased in myopia; however, magnification adjustment is an important
      consideration when using optical coherence tomography (OCT) to evaluate myopic
      eyes. In this study, RNFL thickness and optic nerve head (ONH) size were measured
      in highly myopic eyes with and without magnification adjustments. The
      measurements were compared with magnification-adjusted OCT measurements of
      emmetropic control eyes. METHODS: In this cross-sectional study, RNFL thickness
      (global circle and quadrants) and ONH size (disc and rim areas) were measured in
      one eye of each of 70 participants with high myopia. Magnification-adjusted
      measurements taken in the high myopes were then compared with magnification
      adjusted measurements taken in 70 emmetropic controls. RESULTS: Comparisons of
      magnification-adjusted measurements between highly myopic and emmetropic control
      eyes showed that the highly myopic eyes had significantly thicker global and
      temporal RNFLs (p < 0.05), significantly thinner nasal RNFL (p < 0.05), and
      significantly larger disc and rim areas (p < 0.05). Superior and inferior RNFL
      thickness measurements did not differ significantly between the two groups (p >
      0.05). CONCLUSION: The OCT measurements obtained with magnification adjustment
      show global and temporal RNFL thicknesses and ONH size increase in highly myopic
      eyes.

PMID- 23561006
TI  - Novel amidines and analogues as promising agents against intracellular parasites:
      a systematic review.
AB  - Parasitic protozoa comprise diverse aetiological agents responsible for important
      diseases in humans and animals including sleeping sickness, Chagas disease,
      leishmaniasis, malaria, toxoplasmosis and others. They are major causes of
      mortality and morbidity in tropical and subtropical countries, and are also
      responsible for important economic losses. However, up to now, for most of these
      parasitic diseases, effective vaccines are lacking and the approved
      chemotherapeutic compounds present high toxicity, increasing resistance, limited
      efficacy and require long periods of treatment. Many of these parasitic illnesses
      predominantly affect low-income populations of developing countries for which new
      pharmaceutical alternatives are urgently needed. Thus, very low research funding
      is available. Amidine-containing compounds such as pentamidine are DNA minor
      groove binders with a broad spectrum of activities against human and veterinary
      pathogens. Due to their promising microbicidal activity but their rather poor
      bioavailability and high toxicity, many analogues and derivatives, including pro
      drugs, have been synthesized and screened in vitro and in vivo in order to
      improve their selectivity and pharmacological properties. This review summarizes
      the knowledge on amidines and analogues with respect to their synthesis,
      pharmacological profile, mechanistic and biological effects upon a range of
      intracellular protozoan parasites. The bulk of these data may contribute to the
      future design and structure optimization of new aromatic dicationic compounds as
      novel antiparasitic drug candidates.

PMID- 23561013
TI  - Triclosan enriches for Dehalococcoides-like Chloroflexi in anaerobic soil at
      environmentally relevant concentrations.
AB  - Triclosan is an antimicrobial agent that is discharged to soils with land-applied
      wastewater biosolids, is persistent under anaerobic conditions, and yet its
      impact on anaerobic microbial communities in soils is largely unknown. We
      hypothesized that triclosan enriches for Dehalococcoides-like Chloroflexi because
      these bacteria respire organochlorides and are likely less sensitive, relative to
      other bacteria, to the antimicrobial effects of triclosan. Triplicate anaerobic
      soil microcosms were seeded with agricultural soil, which was not previously
      exposed to triclosan, and were amended with 1 mg kg(-1) of triclosan. Triplicate
      control microcosms did not receive triclosan, and the experiment was run for 618
      days. The overall bacterial community (assessed by automated ribosomal intergenic
      spacer analysis and denaturing gradient gel electrophoresis) was not impacted by
      triclosan; however, the abundance of Dehalococcoides-like Chloroflexi 16S rRNA
      genes (determined by qPCR) increased 20-fold with triclosan amendment compared
      with a fivefold increase without triclosan. This work demonstrates that triclosan
      impacts anaerobic soil communities at environmentally relevant levels.

PMID- 23561015
TI  - [20th Scientific Symposium of the Lilly Foundation: Obesity today. Introduction].

PMID- 23561014
TI  - Inhibition of Streptococcus pneumoniae adherence to human epithelial cells in
      vitro by the probiotic Lactobacillus rhamnosus GG.
AB  - BACKGROUND: Colonization of the nasopharynx by Streptococcus pneumoniae is
      considered a prerequisite for pneumococcal infections such as pneumonia and
      otitis media. Probiotic bacteria can influence disease outcomes through various
      mechanisms, including inhibition of pathogen colonization. Here, we examine the
      effect of the probiotic Lactobacillus rhamnosus GG (LGG) on S. pneumoniae
      colonization of human epithelial cells using an in vitro model. We investigated
      the effects of LGG administered before, at the same time as, or after the
      addition of S. pneumoniae on the adherence of four pneumococcal isolates.
      RESULTS: LGG significantly inhibited the adherence of all the pneumococcal
      isolates tested. The magnitude of inhibition varied with LGG dose, time of
      administration, and the pneumococcal isolate used. Inhibition was most effective
      when a higher dose of LGG was administered prior to establishment of pneumococcal
      colonization. Mechanistic studies showed that LGG binds to epithelial cells but
      does not affect pneumococcal growth or viability. Administration of LGG did not
      lead to any significant changes in host cytokine responses. CONCLUSIONS: These
      findings demonstrate that LGG can inhibit pneumococcal colonization of human
      epithelial cells in vitro and suggest that probiotics could be used clinically to
      prevent the establishment of pneumococcal carriage.

PMID- 23561016
TI  - Specificity of basic information processing and inhibitory control in attention
      deficit hyperactivity disorder.
AB  - BACKGROUND: Both inhibitory-based executive functioning (IB-EF) and basic
      information processing (BIP) deficits are found in clinic-referred attention
      deficit hyperactivity disorder (ADHD) samples. However, it remains to be
      determined whether: (1) such deficits occur in non-referred samples of ADHD; (2)
      they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional
      defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects;
      and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits. METHOD: We
      assessed 704 subjects (age 6-12 years) from a non-referred sample using the
      Development and Well-Being Assessment (DAWBA) and classified them into five
      groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90),
      Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n =
      39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task
      (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a
      diffusion model (DM) to decompose BIP into processing efficiency, speed-accuracy
      trade-off and encoding/motor function along with variability parameters. RESULTS:
      Poorer processing efficiency was found to be specific to ADHD. Faster
      encoding/motor function differentiated ADHD from TDC and from fear/distress
      whereas a more cautious (not impulsive) response style differentiated ADHD from
      both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only
      additive effects. All ADHD-related IB-EF classical effects were fully moderated
      by deficits in BIP. CONCLUSIONS: Our findings challenge the IB-EF hypothesis for
      ADHD and underscore the importance of processing efficiency as the key specific
      mechanism for ADHD pathophysiology.

PMID- 23561017
TI  - Measurement properties of the Patient-Rated Wrist and Hand Evaluation: Rasch
      analysis of responses from a traumatic hand injury population.
AB  - INTRODUCTION: The Patient-Rated Wrist and Hand Evaluation (PRWHE) is a self
      reported assessment of pain and disability to evaluate outcome after hand
      injuries. Rasch analysis is an alternative strategy for examining the
      psychometric properties of a measurement scale based in item response theory,
      rather than classical test theory. PURPOSE OF THE STUDY: This study used Rasch
      analysis to examine the content, scoring and measurement properties of the PRWHE.
      METHODS: PRWHE scores (n = 264) from persons with a traumatic injury or
      reconstructive surgery to one hand were collected from an outpatient hand
      rehabilitation facility. Rasch analysis was conducted to assess how the PRWHE fit
      the Rasch model, confirms the scaling structure of the pain and disability
      subscales, and identifies any areas of bias from differential item functioning.
      RESULTS: Rasch analysis of the PRWHE supports internal consistency of the scale
      (alpha = 0.96) and reliability (as measured by the person separation index) of
      0.95. While gender, age, diagnosis, and duration since injury all systematically
      influenced how people scored the PRWHE, hand dominance and affected side did not.
      Rasch analysis supported a 3 subscale structure (pain, specific activities and
      usual activities) rather than the current divisions of pain and disability.
      CONCLUSIONS: Initial examination of the PRWHE indicates the psychometric
      properties of consistency, reliability and responsiveness previously tested by
      classical methods are further supported by Rasch analysis. It also suggests the
      scale structure may be best considered as 3 subscales rather than simply pain and
      disability.

PMID- 23561018
TI  - Does availability of informal care within the household impact hospitalisation?
AB  - This study assesses the effect of having informal support available at home on
      inpatient care use in Switzerland. The main contributions are to consider the
      availability of care regardless of its source, measured by multiple-adult living
      arrangements, and to examine this effect by type of inpatient care and source of
      potential support. A two-part model with region and time fixed effects is
      estimated to determine the impact of informal care availability on the likelihood
      of hospitalisation and length of stay, conditional on hospitalisation. The
      analysis is conducted on a sample of individuals aged 18+ from four waves of the
      Swiss Household Panel survey (2004-2007). Overall, availability of informal care
      has no impact on the likelihood of hospitalisation but does significantly reduce
      length of stay by 1.9 days. Available support has no effect on the shortest stays
      (up to 10 days), but has a significant impact on acute care stays up to 30 days
      and longer stays. Additionally, the effect does not significantly vary whether
      the source of informal support is a spouse only, a spouse and other adults, or
      other adults only. These results indicate that social changes leading to an
      expansion in the proportion of one-person households may increase future
      inpatient care use. 

PMID- 23561019
TI  - Perinatal outcomes of isolated oligohydramnios at term and post-term pregnancy: a
      systematic review of literature with meta-analysis.
AB  - OBJECTIVE: The management of isolated oligohydramnios (IO) in post/term
      pregnancies is controversial. The aim of this paper was to review outcomes of
      term and post-term pregnancies with IO versus normal amniotic fluid (AF) at labor
      assessment. STUDY DESIGN: A search in PubMed, Medline, EMBASE, and reference
      lists was performed. Inclusion criteria for articles selection: singleton
      pregnancy, definition of olgohydramnios as AFI <5cm, AF assessment at 37-42
      gestational weeks. EXCLUSION CRITERIA: fetal malformations, preterm delivery,
      premature rupture of membranes, intrauterine growth restriction. Perinatal
      outcomes were: obstetric intervention for non-reassuring fetal heart rate
      (cesarean section, operative delivery), meconium-stained AF, Apgar score <7 at
      5min, umbilical artery pH <7.0, small for gestational age infants (SGA),
      admission to neonatal intensive care unit (NICU) and perinatal death. Meta
      analysis compared outcomes of pregnancies with IO vs normal AF. Inter-studies
      heterogeneity was tested. Pooled odds ratio (OR) and 95% confidence interval (95%
      CI) were calculated. Differences between the two groups were considered
      significant if 95% CI did not encompass 1. MOOSE guidelines were followed.
      RESULTS: Four articles provided 679 (17.2%) cases with IO and 3264 (82.8%) with
      normal AF. Obstetric interventions occurred more frequently in the IO than normal
      AF group (IO: 89/679, 13% vs normal; AF: 166/3354, 5%; OR: 2.30; 95% CI: 1.00
      5.29). Meta-analysis did not show differences with regard to meconium, Apgar, pH,
      SGA, NICU and perinatal death. CONCLUSION: In term or post-term pregnancies, IO
      is associated with increased risk of obstetric interventions but outcomes are
      similar to those of pregnancies with normal AF.

PMID- 23561020
TI  - Hysteroscopic hydrosalpinx occlusion with Essure device in IVF patients when
      salpingectomy or laparoscopy is contraindicated.
AB  - OBJECTIVE: To evaluate, in patients with hydrosalpinges, the effect on in vitro
      fertilization (IVF) outcome of the insertion by hysteroscopy of an intratubal
      blocking device, in cases where laparoscopic salpingectomy or laparoscopy was
      contraindicated. STUDY DESIGN: A prospective interventional case series study was
      conducted in fifteen women with unilateral (N=6) or bilateral hydrosalpinges
      (N=9) submitted for IVF. In all of them, laparoscopic salpingectomy was
      contraindicated. Hysteroscopic insertion of the Essure intratubal device in a
      consultation room setting was performed. IVF results were compared with those of
      women where hydrosalpinx was treated by laparoscopic salpingectomy (48 women, 76
      cycles). RESULTS: There were no complications during or immediately after the
      procedure in any of the patients. There were four pregnancies from 16 embryo
      transfers with own oocytes, one spontaneous pregnancy after unilateral Essure
      insertion, and one pregnancy after oocyte donation. In one case the hydrosalpinx
      grew and pelvic inflammatory disease developed 6 months after the insertion,
      requiring bilateral adnexectomy. Although not of statistical significance, IVF
      pregnancy rates were somewhat lower than in the laparoscopic salpingectomy group,
      which was attributed to the lower ovarian reserve before Essure insertion.
      CONCLUSION: The hysteroscopic insertion of the Essure intratubal device prior to
      IVF is a reasonable option in cases where laparoscopic salpingectomy is
      contraindicated. Larger series are required to assess pregnancy outcome.

PMID- 23561021
TI  - Spontaneous ovarian hyperstimulation syndrome: case report, pathophysiological
      classification and diagnostic algorithm.
AB  - Spontaneous ovarian hyperstimulation syndrome is an extremely rare condition that
      occurs in the absence of ovarian hyperstimulation treatment. It can lead to
      significant morbidity and mortality, and therefore early diagnosis and supportive
      treatment are essential. We report an affected mother and her daughter with a
      previously reported heterozygous activating mutation in the FSHR gene. We
      performed a literature review with particular regard to pathogenesis, with a view
      to suggesting a pathophysiological classification system and a diagnostic
      algorithm to assist in the management of this rare condition. 

PMID- 23561022
TI  - Parent-child interaction therapy: a manualized intervention for the therapeutic
      child welfare sector.
AB  - Children who have experienced maltreatment can often display behavioral
      difficulties; their parents may lack disciplinary knowledge, be less sensitive to
      their children, and engage in coercive parenting practices. Parent-child
      interaction therapy (PCIT) is a well-known, evidence-based treatment (EBT) for
      child behavior problems and within the last decade has garnered significant
      evidence to suggest its utility for parents engaged in child maltreatment. This
      article uses a case example to describe PCIT treatment phases and PCIT research
      within the child maltreatment sector is synthesized with particular focus on
      treatment modifications. Successful augmentations and modifications include a
      motivation component, keeping therapeutic time shorter rather than longer, and
      whether to incorporate individual counseling and in-home PCIT are also
      considered. Practical strategies from both a therapeutic and research experience
      are discussed. 

PMID- 23561023
TI  - 5-SPICE: the application of an original framework for community health worker
      program design, quality improvement and research agenda setting.
AB  - INTRODUCTION: Despite decades of experience with community health workers (CHWs)
      in a wide variety of global health projects, there is no established conceptual
      framework that structures how implementers and researchers can understand, study
      and improve their respective programs based on lessons learned by other CHW
      programs. OBJECTIVE: To apply an original, non-linear framework and case study
      method, 5-SPICE, to multiple sister projects of a large, international non
      governmental organization (NGO), and other CHW projects. DESIGN: Engaging a large
      group of implementers, researchers and the best available literature, the 5-SPICE
      framework was refined and then applied to a selection of CHW programs. Insights
      gleaned from the case study method were summarized in a tabular format named the
      '5*5-SPICE charts'. This format graphically lists the ways in which essential CHW
      program elements interact, both positively and negatively, in the implementation
      field. RESULTS: The 5*5-SPICE charts reveal a variety of insights that come from
      a more complex understanding of how essential CHW projects interact and influence
      each other in their unique context. Some have been well described in the
      literature previously, while others are exclusive to this article. An analysis of
      how best to compensate CHWs is also offered as an example of the type of insights
      that this method may yield. CONCLUSIONS: The 5-SPICE framework is a novel
      instrument that can be used to guide discussions about CHW projects. Insights
      from this process can help guide quality improvement efforts, or be used as
      hypothesis that will form the basis of a program's research agenda. Recent
      experience with research protocols embedded into successfully implemented
      projects demonstrates how such hypothesis can be rigorously tested.

PMID- 23561024
TI  - Climate change threats to population health and well-being: the imperative of
      protective solutions that will last.
AB  - BACKGROUND: The observational evidence of the impacts of climate conditions on
      human health is accumulating. A variety of direct, indirect, and systemically
      mediated health effects have been identified. Excessive daily heat exposures
      create direct effects, such as heat stroke (and possibly death), reduce work
      productivity, and interfere with daily household activities. Extreme weather
      events, including storms, floods, and droughts, create direct injury risks and
      follow-on outbreaks of infectious diseases, lack of nutrition, and mental stress.
      Climate change will increase these direct health effects. Indirect effects
      include malnutrition and under-nutrition due to failing local agriculture, spread
      of vector-borne diseases and other infectious diseases, and mental health and
      other problems caused by forced migration from affected homes and workplaces.
      Examples of systemically mediated impacts on population health include famine,
      conflicts, and the consequences of large-scale adverse economic effects due to
      reduced human and environmental productivity. This article highlights links
      between climate change and non-communicable health problems, a major concern for
      global health beyond 2015. DISCUSSION: Detailed regional analysis of climate
      conditions clearly shows increasing temperatures in many parts of the world.
      Climate modelling indicates that by the year 2100 the global average temperature
      may have increased by 34 degrees C unless fundamental reductions in current
      global trends for greenhouse gas emissions are achieved. Given other
      unforeseeable environmental, social, demographic, and geopolitical changes that
      may occur in a plus-4-degree world, that scenario may comprise a largely
      uninhabitable world for millions of people and great social and military
      tensions. CONCLUSION: It is imperative that we identify actions and strategies
      that are effective in reducing these increasingly likely threats to health and
      well-being. The fundamental preventive strategy is, of course, climate change
      mitigation by significantly reducing global greenhouse gas emissions, especially
      long-acting carbon dioxide (CO(2)), and by increasing the uptake of CO(2) at the
      earth's surface. This involves urgent shifts in energy production from fossil
      fuels to renewable energy sources, energy conservation in building design and
      urban planning, and reduced waste of energy for transport, building
      heating/cooling, and agriculture. It would also involve shifts in agricultural
      production and food systems to reduce energy and water use particularly in meat
      production. There is also potential for prevention via mitigation, adaptation, or
      resilience building actions, but for the large populations in tropical countries,
      mitigation of climate change is required to achieve health protection solutions
      that will last.

PMID- 23561025
TI  - Dementia prevalence estimates in sub-Saharan Africa: comparison of two diagnostic
      criteria.
AB  - BACKGROUND: We have previously reported the prevalence of dementia in older
      adults living in the rural Hai district of Tanzania according to the Diagnostic
      and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The
      aim of this study was to compare prevalence rates using the DSM-IV criteria with
      those obtained using the 10/66 diagnostic criteria, which is specifically
      designed for use in low- and middle-income countries. METHODS: In phase I, 1,198
      people aged 70 and older were screened for dementia. A stratified sample of 296
      was then clinically assessed for dementia according to the DSM-IV criteria. In
      addition, data were collected according to the protocol of the 10/66 Dementia
      Research Group, which allowed a separate diagnosis of dementia according to these
      criteria to be established. RESULTS: The age-standardised prevalence of clinical
      DSM-IV dementia was 6.4% (95% confidence interval [CI] 4.9-7.9%) and of '10/66
      dementia' was 21.6% (95% CI 17.5-25.7%). Education was a significant predictor of
      '10/66 dementia', but not of DSM-IV dementia. CONCLUSIONS: There are large
      discrepancies in dementia prevalence rates depending on which diagnostic system
      is used. In rural sub-Saharan Africa, it is not clear whether the association
      between education and dementia using the 10/66 criteria is a genuine effect or
      the result of an educational bias within the diagnostic instrument. Despite its
      possible flaws, the DSM-IV criteria represent an international standard for
      dementia diagnosis. The 10/66 diagnostic criteria may be more appropriate when
      identification of early and mild cognitive impairment is required.

PMID- 23561026
TI  - Addressing research capacity for health equity and the social determinants of
      health in three African countries: the INTREC programme.
AB  - BACKGROUND: The importance of tackling economic, social and health-related
      inequities is increasingly accepted as a core concern for the post-Millennium
      Development Goal framework. However, there is a global dearth of high-quality,
      policy-relevant and actionable data on inequities within populations, which means
      that development solutions seldom focus on the people who need them most. INTREC
      (INDEPTH Training and Research Centres of Excellence) was established with this
      concern in mind. It aims to provide training for researchers from the INDEPTH
      network on associations between health inequities, the social determinants of
      health (SDH), and health outcomes, and on presenting their findings in a usable
      form to policy makers. OBJECTIVE: As part of a baseline situation analysis for
      INTREC, this paper assesses the current status of SDH training in three of the
      African INTREC countries - Ghana, Tanzania, and South Africa - as well as the
      gaps, barriers, and opportunities for training. METHODS: SDH-related courses from
      the three countries were identified through personal knowledge of the
      researchers, supplemented by snowballing and online searches. Interviews were
      also conducted with, among others, academics engaged in SDH and public health
      training in order to provide context and complementary material. Information
      regarding access to the Internet, as a possible INTREC teaching medium, was
      gathered in each country through online searches. RESULTS: SDH-relevant training
      is available, but 1) the number of places available for students is limited; 2)
      the training tends to be public-health-oriented rather than inclusive of the
      broader, multi-sectoral issues associated with SDH; and 3) insufficient funding
      places limitations on both students and on the training institutions themselves,
      thereby affecting participation and quality. We also identified rapidly expanding
      Internet connectivity in all three countries, which opens up opportunities for e
      learning on SDH, though the current quality of the Internet services remains
      mixed. CONCLUSIONS: SDH training is currently in short supply, and there is a
      clear role for INTREC to contribute to the training of a critical mass of African
      researchers on the topic. This work will be accomplished most effectively by
      building on pre-existing networks, institutions, and methods.

PMID- 23561027
TI  - The influence of seasonal climate variability on mortality in pre-industrial
      Sweden.
AB  - BACKGROUND: Recent studies have shown an association between weather and climatic
      factors with mortality, cardiovascular and infectious diseases. We used
      historical data to investigate the impact of seasonal temperature and
      precipitation on total mortality in Uppsala, Sweden, during the first two stages
      of the demographic transition, 1749-1859. DESIGN: We retrieved mortality and
      population numbers of the Uppsala Domkyrka parish from digitised parish records
      and obtained monthly temperature and precipitation measures recorded in Uppsala
      during that time. Statistical models were established for year-to-year
      variability in deaths by annual and seasonal temperature and precipitation,
      adjusting for longer time trends. In a second step, a model was established for
      three different periods to study changes in the association of climate
      variability and mortality over time. Relative risks (RR) with 95% confidence
      intervals (CI) were calculated. RESULTS: Precipitation during spring and autumn
      was significantly associated with annual mortality (spring RR 0.982, CI 0.965
      1.000; autumn RR 1.018, CI 1.004-1.032, respectively, per centimetre increase of
      precipitation). Higher springtime temperature decreased annual mortality, while
      higher summer temperature increased the death toll; however, both were only
      borderline significant (p=0.07). The significant effect of springtime
      precipitation for mortality was present only in the first two periods (1749-1785
      and 1786-1824). On the contrary, the overall effect of autumn precipitation was
      mainly due to its relevance during the last period, 1825-1859 (RR 1.024, CI 0.997
      1.052). At that time, higher winter precipitation was found to decrease
      mortality. CONCLUSIONS: In urban Uppsala, during the 18th and 19th century,
      precipitation appeared to be a stronger predictor for mortality than temperature.
      Higher spring precipitation decreased and higher autumn precipitation increased
      the number of deaths. However, this association differed before and during the
      early stages of industrialisation. Further research shall take age-specific
      differences into account, as well as changes in socio-economic conditions during
      that time.

PMID- 23561028
TI  - Inequity in India: the case of maternal and reproductive health.
AB  - BACKGROUND: Millennium Development Goal (MDG) 5 is focused on reducing maternal
      mortality and achieving universal access to reproductive health care. India has
      made extensive efforts to achieve MDG 5 and in some regions much progress has
      been achieved. Progress has been uneven and inequitable however, and many women
      still lack access to maternal and reproductive health care. OBJECTIVE: In this
      review, a framework developed by the Commission on Social Determinants of Health
      (CSDH) is used to categorize and explain determinants of inequity in maternal and
      reproductive health in India. DESIGN: A review of peer-reviewed, published
      literature was conducted using the electronic databases PubMed and Popline. The
      search was performed using a carefully developed list of search terms designed to
      capture published papers from India on: 1) maternal and reproductive health, and
      2) equity, including disadvantaged populations. A matrix was developed to sort
      the relevant information, which was extracted and categorized based on the CSDH
      framework. In this way, the main sources of inequity in maternal and reproductive
      health in India and their inter-relationships were determined. RESULTS: Five main
      structural determinants emerged from the analysis as important in understanding
      equity in India: economic status, gender, education, social status (registered
      caste or tribe), and age (adolescents). These five determinants were found to be
      closely interrelated, a feature which was reflected in the literature.
      CONCLUSION: In India, economic status, gender, and social status are all closely
      interrelated when influencing use of and access to maternal and reproductive
      health care. Appropriate attention should be given to how these social
      determinants interplay in generating and sustaining inequity when designing
      policies and programs to reach equitable progress toward improved maternal and
      reproductive health.

PMID- 23561029
TI  - Critical realism: a practical ontology to explain the complexities of smoking and
      tobacco control in different resource settings.
AB  - BACKGROUND: This paper presents critical realism (CR) as an innovative system for
      research in tobacco prevention and control. CR argues that underlying mechanisms
      are considered and explored to ensure effective implementation of any
      program/policy or intervention. Any intervention or program/policy that is
      transposed from one country to another or one setting to another is complex.
      METHODS: The research was undertaken and analyzed through a critical ethnography
      lens using CR as a philosophical underpinning. The study relied upon the
      following components: original fieldwork in Nigeria including participant
      observation of smokers, in-depth interviews and focus groups with smokers, and in
      depth interviews with health professionals working in the area of tobacco control
      in Nigeria. RESULTS: Findings from this small ethnographic study in Nigeria,
      suggest that Critical Realism holds promise for addressing underlying mechanism
      that links complex influences on smoking. CONCLUSION: This paper argues that
      understanding the underlying mechanisms associated with smoking in different
      societies will enable a platform for effective implementation of tobacco control
      policies that work in various settings.

PMID- 23561030
TI  - Disadvantaged populations in maternal health in China who and why?
AB  - BACKGROUND: China has made impressive progress towards the Millennium Development
      Goal (MDG) for maternal and reproductive health, but ensuring that progress
      reaches all segments of the population remains a challenge for policy makers. The
      aim of this review is to map disadvantaged populations in terms of maternal
      health in China, and to explain the causes of these inequities to promote policy
      action. METHODS: We searched PUBMED, Popline, Proquest and WanFang and included
      primary studies conducted in mainland China. Experts were also contacted to
      identify additional studies. Disadvantaged populations in terms of MDG 5 and the
      reasons for this disadvantage explored by authors were identified and coded based
      on the conceptual framework developed by the WHO Commission on the Social
      Determinants of Health. RESULTS: In China, differences in maternal health service
      utilization and the maternal mortality ratio among different income groups, and
      among regions with different socio-economic development still exist, although
      these differences are narrowing. Groups with low levels of education and ethnic
      minorities utilize maternal health care less frequently and experience higher
      maternal mortality, although we could not determine whether these differences
      have changed in the last decade. Rural-to-urban migrants use maternal health care
      and contraception to a lower extent than permanent residents of cities, and
      differential maternal mortality shows a widening trend among these groups. Gender
      inequity also contributes to the disadvantaged position of women. Intermediary
      factors that explain these inequities include material circumstances such as long
      distances to health facilities for women living in remote areas, behavioral
      factors such as traditional beliefs that result in reduced care seeking among
      ethnic minorities, and health system determinants such as out-of-pocket payments
      posing financial barriers for the poor. CONCLUSIONS: Inequity in maternal health
      continues to be an issue worthy of greater programmatic and monitoring efforts in
      China.

PMID- 23561031
TI  - Global health post-2015: the case for universal health equity.
AB  - Set in 2000, with a completion date of 2015, the deadline for the Millennium
      Development Goals is approaching, at which time a new global development
      infrastructure will become operational. Unsurprisingly, the discussions on goals,
      topics, priorities and monitoring and evaluation are gaining momentum. But this
      is a critical juncture. Over a decade of development programming offers a unique
      opportunity to reflect on its structure, function and purpose in a contemporary
      global context. This article examines the topic from an analytical health
      perspective and identifies universal health equity as an operational and
      analytical priority to encourage attention to the root causes of unnecessary and
      unfair illness and disease from the perspectives of those for whom the issues
      have most direct relevance.

PMID- 23561032
TI  - Defining and improving quality management in Dutch diabetes care groups and
      outpatient clinics: design of the study.
AB  - BACKGROUND: Worldwide, the organisation of diabetes care is changing. As a result
      general practices and diabetes teams in hospitals are becoming part of new
      organisations in which multidisciplinary care programs are implemented. In the
      Netherlands, 97 diabetes care groups and 104 outpatient clinics are working with
      a diabetes care program. Both types of organisations aim to improve the quality
      of diabetes care. Therefore, it is essential to understand the comprehensive
      elements needed for optimal quality management at organisational level. This
      study aims to assess the current level of diabetes quality management in both
      care groups and outpatient clinics and its improvement after providing feedback
      on their quality management system and tailored support. METHODS/DESIGN: This
      study is a before-after study with a one-year follow-up comparing the levels of
      quality management before and after an intervention to improve diabetes quality
      management. To assess the status of quality management, online questionnaires
      were developed based on current literature. They consist of six domains:
      organisation of care, multidisciplinary teamwork, patient centeredness,
      performance management, quality improvement policy and management strategies.
      Based on the questionnaires, respondents will receive feedback on their score in
      a radar diagram and an elucidating table. They will also be granted access to an
      online toolbox with instruments that proved to be effective in quality of care
      improvement and with practical examples. If requested, personal support in
      implementing these tools will be available. After one year quality management
      will be measured again using the same questionnaire. DISCUSSION: This study will
      reveal a nationwide picture of quality management in diabetes care groups and
      outpatient clinics in the Netherlands and evaluate the effect of offering
      tailored support. The operationalisation of quality management on organisational
      level may be of interest for other countries as well.

PMID- 23561033
TI  - Malaria attacks due to P. vivax or P. ovale in two French military teaching
      hospitals (2000 to 2009).
AB  - CONTEXT: Non-falciparum malaria is less studied than Plasmodium falciparum
      malaria, both in endemic and non-endemic zones. PATIENTS AND METHOD: A
      retrospective study was made of the medical files of patients managed for attacks
      of malaria due to Plasmodium vivax or Plasmodium ovale, between 2000 and 2009, in
      two French military teaching hospitals. RESULTS: Seventy-five percent of attacks
      occurred after a stay in French Guiana, in the Comoros Archipelago, or in the
      Ivory Coast Republic. The most frequent symptoms two months after coming back
      were a flu-like syndrome with headaches, and occasional digestive symptoms,
      without any difference between the first attack and recurrence. One third of
      patients presented with anemia, 78% with thrombocytopenia, and 12% with liver
      dysfunction. DISCUSSION: This study was the most important made in France on
      imported non-falciparum malaria. Military patients and immigrants accounted for a
      majority of patients due to the specificity of military hospitals and local
      recruitment. Clinical and biological features were not specific and did not allow
      guiding the diagnosis. Diagnostic tools were less sensitive for P. ovale.
      CONCLUSION: Patient management could be optimized by more efficient diagnostic
      tools, specific guidelines for the diagnostic and therapeutic management, and a
      dedicated medical training for family practitioners as well as hospitals
      practice.

PMID- 23561034
TI  - Revising the ECRIN standard requirements for information technology and data
      management in clinical trials.
AB  - The pilot phase of the ECRIN (European Clinical Research Infrastructure Network)
      certification programme for European data centres, in late 2011, led to a
      substantial revision of the original ECRIN standards, completed by June 2012. The
      pilot phase, the conclusions drawn from it and the revised set of standards are
      described. Issues concerning the further development of standards and related
      material are discussed, as are the methods available to best support that
      development. A strategy is outlined based on short-lived specific task groups,
      established as necessary by a steering group drawn from ECRIN-ERIC. A final
      section discusses possible future developments.

PMID- 23561035
TI  - Evaluation of a commercial ELISA kit for detection of antibodies against
      Toxoplasma gondii in serum, plasma and meat juice from experimentally and
      naturally infected sheep.
AB  - BACKGROUND: Toxoplasmosis is one of the most common food borne zoonoses
      worldwide, and can be a serious life-threatening disease in the congenitally
      infected fetus and in immunosuppressed patients. Among food animals, sheep along
      with goats and pigs possess the highest incidence of T. gondii cysts in meat, and
      play a major role as a source of human infection. METHODS: In this study, a new
      commercial ELISA kit (PrioCHECK Toxoplasma Ab SR, Prionics Schlieren-Zurich,
      Switzerland) for the detection of anti-T. gondii antibodies in serum, plasma and
      meat juice of sheep, was evaluated by comparing it with the indirect fluorescent
      antibody test (IFAT), indirect haemagglutination test (IHA) and real-time PCR, on
      samples from experimentally inoculated and naturally exposed sheep. RESULTS: The
      commercial ELISA detected the infection status in 50% and 100% of sheep orally
      inoculated with 10,000 T. gondii oocysts (n = 6), from two or three weeks post
      infection (wpi), respectively, both on serum and plasma samples. Meat juice from
      all experimentally inoculated sheep collected at slaughter (12 wpi) showed
      positive ELISA values. In naturally exposed sheep (n = 396), the ELISA showed a
      very good agreement with IFAT (kappa = 0.91-1.0) and IHA (kappa = 0.96-1.0)
      performed on serum; and a positive correlation was observed between ELISA values
      and IFAT titers. By a Receiver Operating Characteristics (ROC) curve analysis,
      the commercial ELISA had relative sensitivities between 93.33% and 100%, and
      relative specificities between 96.87% and 100% respect to IFAT and IHA, depending
      on the considered cut-off value and animal groups tested. Furthermore, the ELISA
      correctly recognized all animals reacting positive in real-time PCR. The ELISA
      results on meat juice agreed with those on serum samples in all experimentally
      inoculated animals, and in 94 out of 96 (97.9%) naturally exposed sheep, when
      meat juice was tested at a 1:10 dilution. CONCLUSION: The commercial ELISA kit
      evaluated in this study could represent a valuable tool to improve the
      surveillance and reporting system for T. gondii in sheep populations at the farm
      level or for diagnosis at the slaughterhouse, contributing to the control of this
      widespread zoonosis.

PMID- 23561036
TI  - Uninterrupted CCTG tracts in the myotonic dystrophy type 2 associated locus.
AB  - Myotonic dystrophy comprises at least two genetically distinct forms, DM1 and
      DM2. DM2 is caused by expansion of the (CCTG)n repeat tract in the CNBP gene. The
      CCTG tract is generally interrupted in healthy range alleles by GCTG, TCTG or
      ACTG motifs. However, alleles with uninterrupted tracts have been reported on
      expanded alleles, and occasionally on large-sized healthy range alleles.
      Therefore, these uninterrupted large-sized alleles have been considered to be
      possible DM2 premutations. In comparison to previous studies, we identified a
      wider range and a higher frequency of healthy range alleles containing
      uninterrupted CCTG tracts. They are most likely not restricted only to large
      alleles, as they constantly exist in the whole spectrum of healthy range alleles.
      Our results indicate that the boundary between stable and unstable uninterrupted
      healthy range alleles is approximately 30 CCTG repeats. This suggests a similar
      distribution of healthy range, premutation and mutation range uninterrupted DM2
      alleles, which is also typical for DM1 alleles. Interrupted alleles, and those
      uninterrupted with less than approximately 30 CCTG repeats, appear stable, while
      instability increases with increasing length of uninterrupted parts above this
      threshold. Unstable DM2 premutation alleles can range from approximately 30 to 55
      CCTG repeats.

PMID- 23561037
TI  - Rapid visual information processing as a cognitive endophenotype of attention
      deficit hyperactivity disorder.
AB  - BACKGROUND: Deficits in sustained attention and reaction time are core features
      of attention deficit hyperactivity disorder (ADHD). However, little is known
      about attention performance in unaffected siblings. Hence, we examined sustained
      attention and reaction time in youths with ADHD, unaffected siblings and controls
      to test whether impaired performance in attention tasks can be a potential
      endophenotype of ADHD. METHOD: We recruited 438 probands with clinical diagnosis
      of ADHD according to DSM-IV criteria, 180 unaffected siblings, and 173 healthy
      controls without lifetime ADHD. They were assessed using psychiatric interviews,
      Conners' Continuous Performance Test, and the tasks involving attention
      performance of the Cambridge Neuropsychological Test Automated Battery (CANTAB):
      Rapid Visual Information Processing (RVP), Reaction Time (RTI) and Match to
      Sample Visual Search (MTS). Multi-level models were used for data analysis.
      RESULTS: Compared with the controls, probands with ADHD and unaffected siblings
      had significantly higher total misses, lower probability of hits in the RVP task
      and probands with ADHD performed worse in the RTI and MTS tasks after controlling
      for sex, age, co-morbidity, parental educational levels and IQ. The duration of
      methylphenidate use and IQ but not psychiatric co-morbidity or current use of
      methylphenidate were associated with deficits in sustained attention in probands
      with ADHD. CONCLUSIONS: Our findings suggest that attention performance assessed
      by the RVP task, but not the RTI or MTS tasks, of the CANTAB may be a useful
      cognitive endophenotype for ADHD genetic studies.

PMID- 23561038
TI  - Inter-observer agreement, diagnostic sensitivity and specificity of animal-based
      indicators of young lamb welfare.
AB  - A scientific literature review and consensus of expert opinion used the welfare
      definitions provided by the Farm Animal Welfare Council (FAWC) Five Freedoms as
      the framework for selecting a set of animal-based indicators that were sensitive
      to the current on-farm welfare issues of young lambs (aged <= 6 weeks). Ten
      animal-based indicators assessed by observation - demeanour, response to
      stimulation, shivering, standing ability, posture, abdominal fill, body
      condition, lameness, eye condition and salivation were tested as part of the
      objective of developing valid, reliable and feasible animal-based measures of
      lamb welfare The indicators were independently tested on 966 young lambs from 17
      sheep flocks across Northwest England and Wales during December 2008 to April
      2009 by four trained observers. Inter-observer reliability was assessed using
      Fleiss's kappa (kappa), and the pair-wise agreement with an experienced, observer
      designated as the 'test standard observer' (TSO) was examined using Cohen's
      kappa. Latent class analysis (LCA) estimated the sensitivity (Se) and specificity
      (Sp) of each observer without assuming a gold standard and predicted the Se and
      Sp of randomly selected observers who may apply the indicators in the future.
      Overall, good levels of inter-observer reliability, and high levels of Sp were
      identified for demeanour (kappa = 0.54, Se >= 0.70, Sp >= 0.98), stimulation
      (kappa = 0.57, Se = 0.30 to 0.77, Sp >= 0.98), shivering (kappa = 0.55, Se = 0.37
      to 0.85, Sp >= 0.99), standing ability (0.54, Se >= 0.80, Sp >= 0.99), posture
      (kappa = 0.45, Se >= 0.56, Sp = 0.99), abdominal fill (kappa = 0.44, Se = 0.39 to
      0.98, Sp = 0.99), body condition (kappa = 0.72, Se ? 0.38 to 0.90, Sp = 0.99),
      lameness (kappa = 0.68, Se > 0.73, Sp = 1.00), and eye condition (kappa = 0.72,
      Se >= 0.86, Sp = 0.99). LCA predicted that randomly selected observers had Se >
      0.77 (acceptable), and Sp >= 0.98 (high) for assessments of demeanour, lameness,
      abdominal fill posture, body condition and eye condition. The diagnostic
      performance of some indicators was influenced by the composition of the study
      population, and it would be useful to test the indicators on lambs with a greater
      level of outcomes associated with poor welfare. The findings presented in this
      paper could be applied in the selection of valid, reliable and feasible
      indicators used for the purposes of on-farm assessments of lamb welfare.

PMID- 23561039
TI  - Prevalence and risk factors of depression in childhood and adolescence as seen in
      four districts of North-Eastern Uganda.
AB  - BACKGROUND: Millions of African children are having to grow up under harsh and
      adverse psychosocial conditions but it's not fully understood how this negative
      psychosocial environment is affecting their mental health. This paper examines
      the prevalence and risk factors of depression in childhood and adolescence as
      seen in a community sample derived from four disadvantaged districts in north
      eastern Uganda. METHODS: 1587 children were assessed using a structured
      instrument administered by trained psychiatric nurses to collect data on
      psychiatric disorders (DSM IV criteria), adverse psychosocial factors and socio
      demographic factors. RESULTS: The point prevalence of depressive disorder
      syndromes (DDS) in this study was 8.6% (95% CI 7.2%-10.1%) with a point
      prevalence for major depressive episode of 7.6% (95% CI 6.3%-9.0%) and dysthymia
      of 2.1% (95% CI 1.5%-3.0%). At multiple logistic regression, the factors that
      were independently significantly associated with DDS were: district (representing
      ecological factors), nature of living arrangements, domestic violence and
      psychiatric co-morbidities/psychiatric problems of emotional distress (assessed
      by the SDQ), suicidality and marginally, anxiety disorder syndromes, eating
      disorder syndromes, motor disorder syndromes and behavioral and developmental
      disorder syndromes (the later being protective against depression). CONCLUSION:
      Disadvantaged north-eastern Uganda had a high prevalence of childhood depressive
      disorders. Ecological factors, markers of the quality of the child-principal
      caregiver relationship (nature of living arrangements and domestic violence) and
      the presence of psychiatric co-morbidities/psychiatric problems were the
      important independent determinants of childhood depression in this study.

PMID- 23561040
TI  - CSF-1R as an inhibitor of apoptosis and promoter of proliferation, migration and
      invasion of canine mammary cancer cells.
AB  - BACKGROUND: Tumor-associated macrophages (TAMs) have high impact on the cancer
      development because they can facilitate matrix invasion, angiogenesis, and tumor
      cell motility. It gives cancer cells the capacity to invade normal tissues and
      metastasize. The signaling of colony-stimulating factor-1 receptor (CSF-1R) which
      is an important regulator of proliferation and differentiation of monocytes and
      macrophages regulates most of the tissue macrophages. However, CSF-1R is
      expressed also in breast epithelial tissue during some physiological stages i.g.:
      pregnancy and lactation. Its expression has been also detected in various
      cancers. Our previous study has showed the expression of CSF-1R in all examined
      canine mammary tumors. Moreover, it strongly correlated with grade of malignancy
      and ability to metastasis. This study was therefore designed to characterize the
      role of CSF-1R in canine mammary cancer cells proliferation, apoptosis,
      migration, and invasion. As far as we know, the study presented hereby is a
      pioneering experiment in this field of veterinary medicine. RESULTS: We showed
      that csf-1r silencing significantly increased apoptosis (Annexin V test),
      decreased proliferation (measured as Ki67 expression) and decreased migration
      ("wound healing" assay) of canine mammary cancer cells. Treatment of these cells
      with CSF-1 caused opposite effect. Moreover, csf-1r knock-down changed growth
      characteristics of highly invasive cell lines on Matrigel matrix, and
      significantly decreased the ability of these cells to invade matrix. CSF-1
      treatment increased invasion of cancer cells. CONCLUSION: The evidence of the
      expression and functional role of the CSF-1R in canine mammary cancer cells
      indicate that CSF-1R targeting may be a good therapeutic approach.

PMID- 23561041
TI  - Lymphoma B-cell responsiveness to CpG-DNA depends on the tumor microenvironment.
AB  - BACKGROUND: Toll-like receptor (TLR) agonists have important properties that can
      be exploited for immunotherapy against tumors. Locally injected immunostimulatory
      oligodeoxynucleotides containing CpG motifs (CpG-ODNs), which are TLR9 agonists,
      have shown promise in cancer models. Several studies have demonstrated that these
      motifs have immunologic effects similar to those of bacterial DNA and can
      stimulate monocytes, macrophages, dendritic, and B cells, which then produce
      several proinflammatory cytokines. However, these CpG-ODNs appear to produce
      opposite effects on tumor B cells. METHODS: In this study, we investigated the
      direct effects of a murine class B CpG (1826) ODNs on lymphoma B cells in vitro
      and in vivo, using mouse models of non-Hodgkin B lymphomas developing in
      immunoprivileged sites, specifically the brain and the eye, and in subcutaneous
      sites. RESULTS: In vitro, CpG-ODNs produced antiproliferative and proapoptotic
      effects on lymphoma B cells. In vivo, it had an antitumor effect when injected
      into tumors in murine models of subcutaneous lymphoma (SCL) and primary cerebral
      lymphoma (PCL). However, its intravitreal administration into a primary
      intraocular lymphoma (PIOL) mouse model did not produce an antitumor effect. In
      vitro experiments using supernatant from mouse PIOL samples demonstrated that the
      PIOL molecular microenvironment inhibits the antiproliferative effect of CpG-ODNs
      on lymphoma B-cells. CONCLUSIONS: Responsiveness to CpG stimulation differs in
      subcutaneous, cerebral, and ocular tumors, according to the tumoral and molecular
      microenvironment, and this should be considered for further therapeutic
      approaches.

PMID- 23561042
TI  - In vivo monitoring of arterially transplanted bone marrow mononuclear cells in a
      rat transient focal brain ischemia model using magnetic resonance imaging.
AB  - OBJECTIVES: Intra-arterial transplantation of bone marrow mononuclear cells
      (BMMCs) effectively improves neuronal function and limits the infarct size. We
      monitored the fate of BMMCs labeled with super paramagnetic iron oxide (SPIO)
      until 7 days after the transplantation using high-field magnetic resonance
      imaging (MRI). METHODS: Male Sprague-Dawley rats were subjected to 90-minute
      focal ischemia using the intraluminal suture technique followed by
      transplantation of 1 * 10(7) BMMCs or vehicle only via the ipsilateral carotid
      artery immediately after reperfusion. Autologous BMMCs were labeled with SPIO by
      electroporation prior to ischemia. MRI studies were performed at 1 hour, 24
      hours, 3 days, and 7 days after reperfusion on each rat. The total infarct volume
      and the volume of negative dots were measured on T2-weighted images and T2*
      weighted images, respectively. RESULTS: One hour after BMMC transplantation, we
      confirmed wide spread distribution of BMMCs in the ischemic hemisphere as a
      negative dot. The volume of negative dot normalized by hemispheric volume
      decreased rapidly and was seldom seen at the seventh day after transplantation.
      The infarct volume was significantly smaller in the transplanted group than the
      vehicle group at 24 hours and 7 days after reperfusion. DISCUSSION: The present
      study established In vivo monitoring of intra-arterial transplanted SPIO-labeled
      BMMCs immediately after reperfusion using MRI of a rat transient focal ischemia
      model. The accumulation of BMMCs in ischemic lesion at the acute stage of
      ischemia can be part of the conditions to limit the infarct size.

PMID- 23561043
TI  - Early stage minimally invasive procedures reduce perihematomal MMP-9 and blood
      brain barrier disruption in a rabbit model of intracerebral hemorrhage.
AB  - INTRODUCTION: The effects of performing a minimally invasive procedure at
      different stages after intracerebral hemorrhage (ICH) on perifocal MMP-9
      expression and blood-brain barrier (BBB) permeability were evaluated. METHODS:
      Thirty-six rabbits were randomly distributed into a normal control group (NC
      group, six rabbits), a model control group (MC group, six rabbits), and a
      minimally invasive group (MI group, 24 rabbits). A model of ICH was established
      in the MC and MI groups. In the MI group, the intracerebral hematoma was
      evacuated by stereotactic minimally invasive procedures over 6 hours (six
      rabbits), 12 hours (six rabbits), 18 hours (six rabbits), and 24 hours (six
      rabbits), following successful induction of ICH. All animals were sacrificed
      within 48 hours after the hematoma was surgically evacuated. A neurological
      deficit score was determined, and the perihematomal MMP-9 level and the BBB
      permeability were measured. RESULTS: The neurological deficit score, the
      perihematomal MMP-9 level, and the BBB permeability of the MI group were
      decreased significantly compared with the MC group. Performing the MI procedure 6
      12 hours after ICH showed the most significant decrease in MMP-9, BBB
      permeability, and neurological deficit score. CONCLUSION: The optimal time window
      of performing MI procedures for the intracerebral hematoma evacuation might be
      within 6-12 hours after hemorrhage.

PMID- 23561044
TI  - Microbicide clinical trial adherence: insights for introduction.
AB  - After two decades of microbicide clinical trials it remains uncertain if
      vaginally- delivered products will be clearly shown to reduce the risk of HIV
      infection in women and girls. Furthermore, a microbicide product with
      demonstrated clinical efficacy must be used correctly and consistently if it is
      to prevent infection. Information on adherence that can be gleaned from
      microbicide trials is relevant for future microbicide safety and efficacy trials,
      pre-licensure implementation trials, Phase IV post-marketing research, and
      microbicide introduction and delivery. Drawing primarily from data and experience
      that has emerged from the large-scale microbicide efficacy trials completed to
      date, the paper identifies six broad areas of adherence lessons learned: (1)
      Adherence measurement in clinical trials, (2) Comprehension of use
      instructions/Instructions for use, (3) Unknown efficacy and its effect on
      adherence/Messages regarding effectiveness, (4) Partner influence on use, (5)
      Retention and continuation and (6) Generalizability of trial participants'
      adherence behavior. Each is discussed, with examples provided from microbicide
      trials. For each of these adherence topics, recommendations are provided for
      using trial findings to prepare for future microbicide safety and efficacy
      trials, Phase IV post-marketing research, and microbicide introduction and
      delivery programs.

PMID- 23561046
TI  - Twin-twin transfusion syndrome and twin anemia-polycythemia sequence in a
      monochorionic triamniotic pregnancy.
AB  - Twin-twin transfusion syndrome (TTTS) is an antenatal complication of
      monochorionic multiple gestations. There have been few studies exploring the role
      of laser photocoagulation or outcomes following treatment in monochorionic
      triplet pregnancies with TTTS. We present a case where TTTS and twin anemia
      polycythemia sequence (TAPS) complicated a monochorionic triplet pregnancy.
      Following the laser photocoagulation to treat the TTTS between the triplets, an
      intra-uterine death occurred in one triplet and TAPS developed in the remaining
      two triplets. Intervention in this case resulted in a 2-week prolongation of
      pregnancy and a positive outcome for the remaining fetuses. This case and other
      published data reviewed in this article suggest that laser photocoagulation has a
      potential role for TTTS in monochorionic triplet pregnancies.

PMID- 23561045
TI  - Peer problems are associated with elevated serum leptin levels in children.
AB  - BACKGROUND: Leptin is thought to act as an important mediator in stress
      reactions. To date, no study has examined the association between psychological
      stress and leptin levels in children. This study aimed to assess the association
      between emotional symptoms and peer problems and serum leptin levels in children
      aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts.
      METHOD: Cross-sectional data from 2827 children aged 10 years were assessed with
      regard to leptin concentrations in serum and behavioral problems using the parent
      reported Strengths and Difficulties Questionnaire (SDQ). Linear regression
      modeling was applied to determine the likelihood of elevated leptin levels in
      children with emotional symptoms and peer problems, controlling for socio
      economic status (SES), body mass index (BMI), fasting serum leptin levels,
      pubertal development and sex hormones. RESULTS: We found that increases in
      emotional symptoms (exp beta adj = 1.03, s.e. = 0.02, p < 0.04) and peer problems
      (exp beta adj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with
      higher serum leptin levels controlled for BMI and sociodemographic factors.
      Similar results were found when the fasting serum leptin sample was examined (exp
      beta adj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a
      significant relationship between serum leptin and peer problems in girls (exp
      beta adj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association
      in boys (exp beta adj = 1.04, s.e. = 0.02, p = 0.05). CONCLUSIONS: Children with
      peer problems have higher stress and eat more, acquire a higher body fat mass and
      thus, through increased leptin resistance, exhibit higher leptin levels.

PMID- 23561047
TI  - The protective effect and underlying mechanism of metformin on neointima
      formation in fructose-induced insulin resistant rats.
AB  - BACKGROUND: Insulin resistance is strongly associated with the development of
      type 2 diabetes and cardiovascular disease. However, the underlying mechanisms
      linking insulin resistance and the development of atherosclerosis have not been
      fully elucidated. Moreover, the protective effect of antihyperglycemic agent,
      metformin, is not fully understood. This study investigated the protective
      effects and underlying mechanisms of metformin in balloon-injury induced stenosis
      in insulin resistant rats. METHODS: After 4 weeks high fructose diet, rats
      received balloon catheter injury on carotid arteries and were sacrificed at 1 and
      4 weeks post injury. Biochemical, histological, and molecular changes were
      investigated. RESULTS: Plasma levels of glucose, insulin, total cholesterol,
      triglyceride, free fatty acids, and methylglyoxal were highly increased in
      fructose-induced insulin resistant rats and treatment with metformin
      significantly improved this metabolic profile. The neointimal formation of the
      carotid arteries was enhanced, and treatment with metformin markedly attenuated
      neointimal hyperplasia. A significant reduction in BrdU-positive cells in the
      neointima was observed in the metformin-treated group (P<0.01). Insulin signaling
      pathways were inhibited in insulin resistant rats while treatment with metformin
      enhanced the expression of insulin signaling pathways. Increased expression of
      JNK and NFKB was suppressed following metformin treatment. Vasoreactivity was
      impaired while treatment with metformin attenuated phenylephrine-induced
      vasoconstriction and enhanced methacholine-induced vasorelaxation of the balloon
      injured carotid arteries in insulin resistant rats. CONCLUSION: The balloon
      injury induced neointimal formation of the carotid arteries is enhanced by
      insulin resistance. Treatment with metformin significantly attenuates neointimal
      hyperplasia through inhibition of smooth muscle cell proliferation, migration,
      and inflammation as well as by improvement of the insulin signaling pathway.

PMID- 23561049
TI  - Correction: A survey of foot problems in community-dwelling older Greek
      Australians.

PMID- 23561048
TI  - Molecular clonality and antimicrobial resistance in Salmonella enterica serovars
      Enteritidis and Infantis from broilers in three Northern regions of Iran.
AB  - BACKGROUND: Multidrug-resistant Salmonella strains are frequently encountered
      problems worldwide with considerable increased occurrences in recent years. The
      aim of this study was to investigate the occurrence and frequency of
      antimicrobial resistance and associated resistance genes in Salmonella isolates
      from broiler farms in different regions of Iran covering a time period of four
      years. RESULTS: From 2007 to 2011, 36 Salmonella strains were isolated from
      broiler farms located in three northern provinces of Iran. The isolates were
      serotyped, antimicrobial susceptibility tested, and characterized for
      antimicrobial resistance genes associated to the phenotype. Pulsed-field gel
      electrophoresis (PFGE) was applied for comparison of genetic relatedness.Two
      serovars were detected among the isolates; Salmonella enterica serovar Infantis
      (75%) and S. Enteritidis (25%). Thirty-four (94%) of the isolates exhibited
      resistance to nalidixic acid and ciprofloxacin caused by a single mutation in the
      quinolone resistance-determining region (QRDR) of gyrA. For all strains this
      mutation occurred in the codon of Asp87 leading to a Asp87-Tyr, Asp87-Gly or
      Asp87-Asn substitutions. All S. Infantis (n = 27) were resistant to tetracycline,
      spectinomycin, streptomycin, and sulfamethoxazole and harbored the associated
      resistance genes; tetA, dfrA14, aadA1, and sulI together with class 1 integrons.
      The isolates revealed highly similar PFGE patterns indicating clonal relatedness
      across different geographical locations. CONCLUSION: The data provided
      fundamental information applicable when launching future control programs for
      broilers in Iran with the aim to conserve the effectiveness of important
      antimicrobials for treatment in humans.

PMID- 23561050
TI  - A behavioral genetic analysis of alexithymia and the Dark Triad traits of
      personality.
AB  - The present study is the first to assess phenotypic correlations between
      alexithymia and the Dark Triad traits of personality in a community sample, as
      well as the common genetic and environmental factors underlying these
      correlations. Participants were 232 North American adult twin pairs who completed
      the Narcissistic Personality Inventory, the Self-Report Psychopathy Scale, the
      MACH-IV, and the Toronto Alexithymia Scale. Results revealed that alexithymia
      correlates significantly and positively with psychopathy and Machiavellianism,
      and negatively with narcissism. Subsequent bivariate behavioral genetic analysis
      demonstrated that these phenotypic correlations were primarily attributable to
      common genetic and common non-shared environmental factors. The implication of
      these findings regarding the maladaptive functions of alexithymia within the
      antisocial realm of behavior and the need for replication are discussed.

PMID- 23561051
TI  - Association of angiotensin-converting enzyme insertion/deletion polymorphism
      (rs4646994) with the risk of primary intracerebral hemorrhage.
AB  - BACKGROUND: Evidence has suggested that angiotensin-converting enzyme (ACE) may
      be involved in the etiology of primary intracerebral hemorrhage (PICH), but the
      underlying association between ACE I/D (rs4646994) polymorphism and PICH risk is
      still ambiguous. This meta-analysis was performed to quantitatively summarize the
      evidence for such a relationship. METHODS: Eligible studies were identified by
      searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM
      (Chinese biomedical literature database), and WANFANG databases within a range of
      published years from 1990 to August 2012. The odds ratio (OR) corresponding to
      the 95% confidence interval (CI) was used to assess the different associations.
      RESULTS: A total of 28 studies with 2806 cases and 3612 controls were included in
      this meta-analysis. The pooled examination displayed an overall increased PICH
      risk associated with ACE I/D polymorphism in a recessive model (OR = 1.80, 95% CI
      = 1.39-2.33, P < 0.001 for DD versus ID/II), however, this association was only
      present in Asians (OR = 1.91, 95% CI = 1.45-2.51, P < 0.001) and not in
      Caucasians (OR = 1.16, 95% CI = 0.55-2.44, P = 0.69). Hypertensive intracerebral
      hemorrhage (HICH) had a much greater risk (OR = 4.26, 95% CI = 2.87-6.32, P <
      0.001) than general PICH (OR = 1.65, 95% CI = 1.25-2.18, P < 0.001) in Asians,
      and subgroup with controls excluding hypertension had a greater risk (OR = 2.65,
      95% CI = 1.78-3.95, P < 0.001) than that including hypertension (OR = 1.50, 95%
      CI = 1.12-2.02, P = 0.01). CONCLUSIONS: This meta-analysis suggests that DD
      homozygote of ACE I/D polymorphism has an increased PICH risk in Asians, and may
      have a synergistic effect with hypertension.

PMID- 23561052
TI  - Aetiology and clinical features of dysentery in children aged <5 years in rural
      Bangladesh.
AB  - The study identified the common aetiological agents and prominent clinical
      features of dysentery cases in children aged <5 years and compared this to non
      dysentery diarrhoeal cases from the same population. From January 2010 to
      December 2011, 2324 children aged <5 years received treatment at Kumudini
      Hospital, of which 682 (29%) presented with dysentery. Of the dysenteric
      children, aetiology could not be determined for over half (61%). Shigella spp.
      accounted for 32% of dysentery cases. Significant associations were found between
      presence of blood in stool and: child age (24-59 months) [odds ratio (OR) 2.21,
      95% confidence interval (CI) 1.49-3.27], no treatment of drinking water at home
      (OR 2.00, 95% CI 1.09-3.67), vomiting (OR 0.19, 95% CI 0.14-0.25), abdominal pain
      (OR 4.68, 95% CI 3.24-6.77), straining (OR 16.45, 95% CI 11.92-22.69), wasting
      (OR 1.66, 95% CI 1.15-2.41), and presence of Shigella in stool (OR 6.25, 95% CI
      4.20-9.29) after controlling for confounders. This study makes it clear that
      appropriate public health strategies are needed to reduce the burden of dysentery
      in Bangladesh.

PMID- 23561053
TI  - Oral immunization with Lactococcus lactis secreting attenuated recombinant
      staphylococcal enterotoxin B induces a protective immune response in a murine
      model.
AB  - BACKGROUND: Staphylococcus aureus is unrestrictedly found in humans and in animal
      species that maintain thermal homeostasis. Inadequate cleaning of processing
      equipment or inappropriate handling can contaminate processed food and cause
      severe food poisoning. Staphylococcal enterotoxin B (SEB), a potent
      superantigenic exotoxin, is produced by 50% of clinical isolates of S. aureus and
      is associated with massive food poisoning and with the induction of toxic shock
      syndrome. RESULTS: A gene sequence encoding a recombinant SEB (rSEB), devoid of
      superantigenic activity, was successfully cloned and expressed in a cytoplasmic
      or a secreted form in the food-grade lactic acid bacterium Lactococcus lactis.
      The recombinant protein detected in the cytoplasm or in the culture medium
      exhibited the expected molecular mass and was recognized by a SEB-polyclonal
      antibody. Oral immunization with the recombinant L. lactis strains induced a
      protective immune response in a murine model of S. aureus infection. Immunized
      mice survived intraperitoneal challenge with an S. aureus SEB-producer strain.
      Counts of S. aureus in the spleen of rSEB-immunized mice were significantly
      reduced. The rSEB-immunized mice showed significant titers of anti-SEB IgA and
      IgG in stools and serum, respectively. Both recombinant L. lactis strains were
      able to elicit cellular or systemic immune responses in mice, with no significant
      difference if rSEB was produced in its cytoplasmic or secreted form. However,
      recombinant L. lactis expressing the cytoplasmic rSEB increased the survival rate
      of the challenged mice by 43%. CONCLUSIONS: These findings show the vaccine
      efficacy of L. lactis carrying an attenuated SEB, in a murine model, following
      lethal S. aureus challenge.

PMID- 23561054
TI  - Teaching medical students a clinical approach to altered mental status:
      simulation enhances traditional curriculum.
AB  - INTRODUCTION: Simulation-based medical education (SBME) is increasingly being
      utilized for teaching clinical skills in undergraduate medical education. Studies
      have evaluated the impact of adding SBME to third- and fourth-year curriculum;
      however, very little research has assessed its efficacy for teaching clinical
      skills in pre-clerkship coursework. To measure the impact of a simulation
      exercise during a pre-clinical curriculum, a simulation session was added to a
      pre-clerkship course at our medical school where the clinical approach to altered
      mental status (AMS) is traditionally taught using a lecture and an interactive
      case-based session in a small group format. The objective was to measure
      simulation's impact on students' knowledge acquisition, comfort, and perceived
      competence with regards to the AMS patient. METHODS: AMS simulation exercises
      were added to the lecture and small group case sessions in June 2010 and 2011.
      Simulation sessions consisted of two clinical cases using a high-fidelity full
      body simulator followed by a faculty debriefing after each case. Student
      participation in a simulation session was voluntary. Students who did and did not
      participate in a simulation session completed a post-test to assess knowledge and
      a survey to understand comfort and perceived competence in their approach to AMS.
      RESULTS: A total of 154 students completed the post-test and survey and 65 (42%)
      attended a simulation session. Post-test scores were higher in students who
      attended a simulation session compared to those who did not (p<0.001). Students
      who participated in a simulation session were more comfortable in their overall
      approach to treating AMS patients (p=0.05). They were also more likely to state
      that they could articulate a differential diagnosis (p=0.03), know what initial
      diagnostic tests are needed (p=0.01), and understand what interventions are
      useful in the first few minutes (p=0.003). Students who participated in a
      simulation session were more likely to find the overall AMS curriculum useful
      (p<0.001). CONCLUSION: Students who participated in a simulation exercise
      performed better on a knowledge-based test and reported increased comfort and
      perceived competence in their clinical approach to AMS. SBME shows significant
      promise for teaching clinical skills to medical students during pre-clinical
      curriculum.

PMID- 23561056
TI  - MRI-3D ultrasound-X-ray image fusion with electromagnetic tracking for
      transendocardial therapeutic injections: in-vitro validation and in-vivo
      feasibility.
AB  - Myocardial infarction (MI) is one of the leading causes of death in the world.
      Small animal studies have shown that stem-cell therapy offers dramatic functional
      improvement post-MI. An endomyocardial catheter injection approach to therapeutic
      agent delivery has been proposed to improve efficacy through increased cell
      retention. Accurate targeting is critical for reaching areas of greatest
      therapeutic potential while avoiding a life-threatening myocardial perforation.
      Multimodal image fusion has been proposed as a way to improve these procedures by
      augmenting traditional intra-operative imaging modalities with high resolution
      pre-procedural images. Previous approaches have suffered from a lack of real-time
      tissue imaging and dependence on X-ray imaging to track devices, leading to
      increased ionizing radiation dose. In this paper, we present a new image fusion
      system for catheter-based targeted delivery of therapeutic agents. The system
      registers real-time 3D echocardiography, magnetic resonance, X-ray, and
      electromagnetic sensor tracking within a single flexible framework. All system
      calibrations and registrations were validated and found to have target
      registration errors less than 5 mm in the worst case. Injection accuracy was
      validated in a motion enabled cardiac injection phantom, where targeting accuracy
      ranged from 0.57 to 3.81 mm. Clinical feasibility was demonstrated with in-vivo
      swine experiments, where injections were successfully made into targeted regions
      of the heart.

PMID- 23561057
TI  - Assessment of dynamic contrast-enhanced magnetic resonance imaging in the
      differentiation of malignant from benign orbital masses.
AB  - OBJECTIVE: Dynamic contrast enhanced MR imaging (DCE-MRI) allows imaging of the
      physiology of the microcirculation. The purpose of this study was to determine
      the diagnostic efficacy of time intensity curve (TIC) and DCE parameters for
      characterization of orbital masses. METHODS: Fifty-nine patients with untreated
      orbital lesions underwent DCE-MRI before surgery. For each lesion, peak height
      (PH), maximum enhancement ratio (ERmax), time of peak enhancement (Tpeak) and
      maximum rise slope (Slopemax) were plotted and calculated. Receiver operator
      characteristics (ROC) analysis was conducted to assess the appropriate cut-off
      value. RESULTS: All 26 lesions that demonstrated persistent pattern (type-I) TICs
      were benign. Most of the masses with the washout pattern (type-III) TIC were
      malignant (10/14), including lymphoma (n=6) and melanoma (n=4). The Slopemax of
      benign lesions was statistically lower than malignant ones, while the ERmax and
      Tpeak values of benign lesions were significantly higher. No statistical
      difference was found in PH (P=0.121). The AUC for ERmax, Tpeak and Slopemax in
      differentiating benign orbital lesions from malignant ones were 0.683, 0.837 and
      0.738, respectively. In the three DCE parameters, Slopemax cut-off value of 1.10
      provided the highest sensitivity of 93.8%; however, the corresponding specificity
      was low (58.1%). The ERmax cut-off value of 1.37 and Tpeak cut-off value of 35.14
      respectively offered the best diagnostic performances. CONCLUSION: DCE-MRI,
      especially the qualitative TIC pattern and quantitative value of Slopemax, ERmax
      and Tpeak, could be a complementary investigation in distinguishing malignant
      orbital tumor from benign ones.

PMID- 23561059
TI  - Universal screening to identify gestational diabetes: a multi-centre study in the
      North of England.
AB  - We conducted an audit of treatment and outcomes in 116 women with gestational
      diabetes. These women received intense monitoring and high levels of medical and
      obstetric intervention. 24% would not have been identified by risk factor based
      screening. Cost effective strategies to identify all women with gestational
      diabetes are needed.

PMID- 23561058
TI  - How phenotype and developmental stage affect the genes we find: GABRA2 and
      impulsivity.
AB  - CONTEXT: The detection and replication of genes involved in psychiatric outcome
      has been notoriously difficult. Phenotypic measurement has been offered as one
      explanation, although most of this discussion has focused on problems with binary
      diagnoses. OBJECTIVE: This article focuses on two additional components of
      phenotypic measurement that deserve further consideration in evaluating genetic
      associations: (1) the measure used to reflect the outcome of interest, and (2)
      the developmental stage of the study population. We focus our discussion of these
      issues around the construct of impulsivity and externalizing disorders, and the
      association of these measures with a specific gene, GABRA2. DESIGN, SETTING, AND
      PARTICIPANTS: Data were analyzed from the Collaborative Study on the Genetics of
      Alcoholism Phase IV assessment of adolescents and young adults (ages 12-26; N =
      2,128). MAIN OUTCOME MEASURES: Alcohol dependence, illicit drug dependence,
      childhood conduct disorder, and adult antisocial personality disorder symptoms
      were measured by psychiatric interview; Achenbach youth/adult self-report
      externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity
      scale; NEO extraversion and consciousness. RESULTS: GABRA2 was associated with
      subclinical levels of externalizing behavior as measured by the Achenbach in both
      the adolescent and young adult samples. Contrary to previous associations in
      adult samples, it was not associated with clinical-level DSM symptom counts of
      any externalizing disorders in these younger samples. There was also association
      with sensation-seeking and extraversion, but only in the adolescent sample. There
      was no association with the Barratt impulsivity scale or conscientiousness.
      CONCLUSIONS: Our results suggest that the pathway by which GABRA2 initially
      confers risk for eventual alcohol problems begins with a predisposition to
      sensation-seeking early in adolescence. The findings support the heterogeneous
      nature of impulsivity and demonstrate that both the measure used to assess a
      construct of interest and the age of the participants can have profound
      implications for the detection of genetic associations.

PMID- 23561060
TI  - Serum agonistic autoantibodies against type-1 angiotensin II receptor titer in
      patients with epithelial ovarian cancer: a potential role in tumor cell migration
      and angiogenesis.
AB  - BACKGROUND: Although agonistic autoantibodies against type-1 angiotensin-II
      receptor (AT1-AA) are frequently detected in women with preeclampsia, the
      clinical significance of AT1-AA in association with epithelial ovarian cancer
      (EOC) has not been identified. METHODS: In an attempt to clarify this issue, we
      measured serum AT1-AA titer from EOC patients (n = 89) and healthy normal
      subjects (n = 55), correlated AT1-AA titer with EOC stage and grade, and
      demonstrated the effects of purified AT1-AA on migration of ovarian cancer cells
      and angiogenesis of chick embryo chorioallantoic membrane. RESULTS: We found that
      the AT1-AA titer was significantly higher in EOC patients compared with healthy
      control subjects (1.77 +/- 0.28 vs. 0.35 +/- 0.05, P < 0.01). The positive rate
      was averaged by 72.1+/-2.5% in EOC patients and 15.5 +/-1.5% in control (P <
      0.01). Increased AT1-AA titer in EOC patients was associated with advanced stages
      and grades of EOC, and positively correlated with level of vascular endothelial
      growth factor (r = 0.855, P < 0.01). Furthermore, AT1-AA directly stimulated
      migration of ovarian cancer cells and enhanced microvascular density of chick
      embryo chorioallantoic membrane. These AT1-AA-mediated effects were significantly
      blocked either by an autoantibody-neutralizing peptide or an angiotensin II type
      I receptor antagonist, losartan. CONCLUSION: Taken together, we found that a
      higher serum AT1-AA titer may be associated with advanced progression of EOC in
      patients and play an important role in development of EOC by promoting cancer
      cell migration and angiogenesis. These findings implicate that AT1-AA might be
      selected as a detectable biomarker and potential therapeutic target in diagnosis
      and treatment of EOC patients.

PMID- 23561061
TI  - Exploratory study on the efficacy of reflexology for pain threshold and tolerance
      using an ice-pain experiment and sham TENS control.
AB  - OBJECTIVES: To explore the efficacy of reflexology on acute pain induced in
      healthy human subjects using a sham TENS control. DESIGN: An ice-pain experiment
      was undertaken in which the volunteers (n = 15; 11 female and 4 male with a mean
      +/- SEM age of 37.7 +/- 2.6 years) were required to immerse their non-dominant
      hand in a container of ice-slurry whilst two indices of pain, i.e. threshold,
      (the time taken for subjects to experience the first pain sensation) and
      tolerance, (the time when the subject is unable to tolerate any further pain),
      were measured. RESULTS: Compared to control data, reflexology increased acute
      pain threshold (F(1,14) = 4.5958, p < 0.05) and tolerance (F(1,14) = 5.1095, p <
      0.05). CONCLUSIONS: These findings demonstrate that reflexology produces
      antinociceptive effects in a controlled experiment and suggest the possibility
      that reflexology may be useful on its own or as an adjunct to medication in the
      treatment of pain conditions in man.

PMID- 23561062
TI  - An exploration of Traditional Chinese Medicine practitioners' perceptions of
      Evidence Based Medicine.
AB  - OBJECTIVES: To explore understanding of Evidence Based Medicine (EBM) and use of
      evidence by Traditional Chinese Medicine (TCM) practitioners, practising in
      Scotland. DESIGN: Qualitative study incorporating semi-structured interviewing of
      12 TCM practitioners practising TCM in Scotland. SETTING: TCM practitioners'
      premises in an urban area of Scotland, UK. RESULTS: Few participants were aware
      of the process of EBM but all reported importance of learning from a range of
      sources including patients and practice. Participants reported no involvement in
      the wider demands of the EBM process. CONCLUSIONS: TCM practice here was informed
      by a range of sources but many barriers to full engagement with the EBM process
      were evident and the small business model of service delivery seemed important
      here. Participants' prioritisation of classical books and practice as evidence
      sources poses some cause for concern at a time of rapid growth in well evidenced
      western biomedical and TCM knowledge and practice.

PMID- 23561063
TI  - Perception and attitude of Jordanian physicians towards complementary and
      alternative medicine (CAM) use in oncology.
AB  - PURPOSE: To determine general perception and attitudes to CAM among Jordanian
      physicians at King Hussein Cancer Center (KHCC), and challenges facing formal
      integration of CAM into conventional practice. METHOD: A cross-sectional survey
      of KHCC physicians using a semi-structured questionnaire. RESULTS: Response rate
      was 71%(71/100). 84%(41/49) defined CAM as "not evidence-based" treatments and/or
      "Herbs". More than 80% reported interest to learn about CAM. 70% believed that
      herbal remedies were harmful, though only 17%(12/71) reported some knowledge
      about their composition. Physicians' concern of harmful interactions was the most
      significant reason for asking their patients about use (p < 0.0001). >90%(32/35)
      of physicians who estimated a low rate (<10%) of CAM usage by patients had
      minimal knowledge of herbal remedies (p = 0.06). CONCLUSION: KHCC physicians have
      very little knowledge but high interest to learn about CAM use in oncology. An
      educational component will be crucial for the implementation of a formal CAM
      program at KHCC.

PMID- 23561064
TI  - The impact of Yoga upon young adult cancer survivors.
AB  - This study explored the use of Yoga by using a cross-sectional analysis of 286
      young adult cancer survivors. The aim was to explore yoga practice, reasons for
      using this therapy; predictors of yoga use and any potential relationship between
      yoga use and well-being. Ninety one participants (32.82%) reported practicing
      yoga from their initial diagnosis. Practitioners reported a relatively high
      intensity (mean: 7.46 h/month) and length (25.88 months) of practice. The most
      common reasons given for undertaking yoga were to maintain flexibility and
      promote relaxation. Sociodemographic predictors of yoga use included gender,
      higher education with increased yoga use generally related to enhanced feelings
      of well-being. Results suggest that yoga use is more commonly used by cancer
      survivors with greater resources. Understanding more about the use of yoga by
      cancer survivors may facilitate the development and promotion of yoga-based
      interventions.

PMID- 23561065
TI  - Reconditioning the stress response with hypnosis CD reduces the inflammatory
      cytokine IL-6 and influences resilience: a pilot study.
AB  - AIM: The aim of this investigation was to measure the impact of a self
      administered hypnosis intervention on resilience and the inflammatory cytokine IL
      6. METHOD: Over a period of 12 weeks, 11 participants listened to a self
      administered hypnosis stress reduction program designed to recondition and
      improve participants' emotional and physical reactions to perceived work and life
      stressors. Subjects were administered subjective measures of coping, resilience,
      and stress tolerance, as well as, IL-6, an objective blood measure of
      inflammatory activity. RESULTS: After 12 weeks, participants were observed to
      have a significantly lower IL-6 serum level from baseline. Further, participants
      reported a significant decrease in the use of negative appraisal coping (such as,
      self-deprecating statements, perfectionism, and catastrophic and pessimistic
      thinking), and an improvement in eating/nutritional habits following the
      intervention. Baseline eating/nutritional habits and threat minimization coping
      significantly predicted a change in serum IL-6 over the course of the
      intervention in stepwise hierarchical regression analyses. CONCLUSION: Pilot
      study provides support that a brief self-administered CD hypnosis stress
      reduction program can modify a physiological measure of inflammation (IL-6), and
      improve coping and resilience in the face of work and life stress.

PMID- 23561066
TI  - Mindful-Veteran: the implementation of a brief stress reduction course.
AB  - BACKGROUND: Stress reduction is a focus of healthcare management in Veterans who
      often faced extreme stressors during military service. OBJECTIVE: A quality
      improvement project to evaluate the implementation and effects of a brief
      mindfulness course delivered to Veterans, Mindful-Veteran (M-Vet), with self
      reported mild to severe depressive symptoms in an outpatient setting. DESIGN: A
      within-subjects design was used to determine whether depressed Veterans enrolled
      in a 6-week M-Vet course report improvements in perceived stress, depressive
      symptoms, and quality of life. RESULTS: Mental health, general health, emotional
      role, and social functioning quality of life subscales significantly improved
      over the 6-week course. Severity of stress and depressive symptom scores,
      however, did not significantly decrease. CONCLUSION: The findings suggest that
      this brief, simplified mindfulness program designed for military Veterans, seen
      within a community based outpatient clinic, has clinically beneficial effects on
      psychiatric outcomes.

PMID- 23561067
TI  - Effect of daily supplementation of fruits on oxidative stress indices and
      glycaemic status in type 2 diabetes mellitus.
AB  - This study sought to examine whether consumption of two low-calorie fruit/day for
      3-months can effectively improve oxidative stress, anthropometry, blood pressure
      and glycaemic control in type 2 diabetes mellitus. Study involved 123 patients
      who were assigned to receive either standard care or with additional dietary
      therapy. Dietary intervention resulted in significant reduction in
      malondialdehyde, plasma glucose, glycated haemoglobin and improvement in
      antioxidants like vitamin C and reduced glutathione when compared to controls.
      Mean plasma levels of vitamin C increased by 64% (p < 0.001). There were no
      differences in waist circumference, waist-to-hip ratio, blood pressure, vitamin E
      and superoxide dismutase in the intervention group at follow-up. Diet rich in
      fruits can improve some antioxidants which are likely to reduce oxidative stress
      in type 2 diabetes. Regular consumption of fruits can lower the glycaemic status
      in these patients. The study supports the usefulness of plasma vitamin C as a
      biomarker for fruit intake.

PMID- 23561068
TI  - Rheumatoid arthritis in upper limbs benefits from moderate pressure massage
      therapy.
AB  - METHODS: Forty-two adults with rheumatoid arthritis in the upper limbs were
      randomly assigned to a moderate pressure or a light pressure massage therapy
      group. A therapist massaged the affected arm and shoulder once a week for a 4
      week period and also taught the participant self-massage to be done once daily.
      RESULTS: The moderate pressure vs. the light pressure massage therapy group had
      less pain and perceived greater grip strength following the first and last
      massage sessions. By the end of the one month period the moderate pressure
      massage group had less pain, greater grip strength and greater range of motion in
      their wrist and large upper joints (elbows and shoulders).

PMID- 23561069
TI  - A qualitative analysis of beginning mindfulness experiences for women with post
      traumatic stress disorder and a history of intimate partner violence.
AB  - This article presents the beginning mindfulness experiences of low income,
      minority women with a history of intimate partner violence. Ten women
      participated in a Mindfulness-Based Stress Reduction group, three interviews and
      a focus group over 15 months. Using an interpretive phenomenological analysis
      approach, we derived the following themes: struggles to practice meditation; a
      vision of growing and helping; personal improvements, and interpersonal
      improvements. We share recommendations for clinical practice.

PMID- 23561070
TI  - Antioxidant capacity of anthocyanins from Rhodomyrtus tomentosa (Ait.) and
      identification of the major anthocyanins.
AB  - The anthocyanins in the fruits of Rhodomyrtus tomentosa (ACN) were extracted by
      1% TFA in methanol, and then purified by X-5 resin column and C18 (SPE)
      cartridges. The purified anthocyanin extract (ART) from the fruits of R.
      tomentosa showed strong antioxidant activities, including DPPH radical-scavenging
      capacity, ABTS radical scavenging capacity, reducing power and oxygen radical
      absorbance capacity (ORAC). The purified anthocyanin extract was analyzed by high
      performance liquid chromatography (HPLC). The major anthocyanins were purified by
      semi-preparative HPLC and Sephadex LH-20 column chromatography, and were
      identified as cyanidin-3-O-glucoside, peonidin-3-O-glucoside, malvidin-3-O
      glucoside, petunidin-3-O-glucoside, delphinidin-3-O-glucoside and pelargonidin-3
      glucoside by HPLC-ESI/MS and nuclear magnetic resonance spectroscopy (NMR).
      Cyanidin-3-O-glucoside was considered as the most abundant anthocyanin, which was
      29.4 mg/100 g dry weight of R. tomentosa fruits. Additionally, all the major
      anthocyanins were identified from R. tomentosa fruit for the first time.

PMID- 23561071
TI  - Effects of combination processes on the extraction of pectins from rapeseed cake
      (Brassica napus L.).
AB  - In this study, rapeseed cake (RSC) was used as a source of pectins due to its
      high carbohydrate content. Different combinations of treatments were applied to
      investigate the effect of combination processes on the extraction of pectin from
      RSC. The treatments chosen for combination were a fat removal process (FRP)
      (solvent extraction using an alcohol-benzene mixture), a chemical treatment (CT)
      (hydrolysis using 1% hydrochloric acid), and an enzymatic hydrolysis (EH). After
      the combined processes, pectins were extracted by isopropanol/ethanol
      precipitation and the residues were analysed by HPLC or an elemental analyser.
      The pectin yields and galacturonic acid contents were increased by FRP because
      72.13% of the total fat was removed; additionally, EH had a similar effect.
      However, CT decreased the yields because the treatment was too harsh and the
      galacturonic acid broke down. Pectin yields and galacturonic acid contents were
      highest in the combination process FRP/EH (6.23% and 64.23%, respectively).

PMID- 23561072
TI  - Intake of mulberry 1-deoxynojirimycin prevents diet-induced obesity through
      increases in adiponectin in mice.
AB  - In this study, the anti-obesity effect of 1-deoxynojirimycin (DNJ) was examined
      in the diet-induced obese mouse model. Mulberry DNJ was administered to the obese
      mice for 12 weeks. As a result, DNJ decreased both the visceral fat weight and
      adipocyte size. To determine the influence of DNJ on lipid metabolism, lipid
      parameters of the plasma and the liver and the activities of several molecules
      related to lipid metabolism in the liver were measured. DNJ activated the beta
      oxidation system, suppressed lipid accumulation in the liver and reduced plasma
      triacylglycerol. Since it was thought that the factor activated in the beta
      oxidation system was adiponectin, plasma adiponectin levels were measured and it
      was shown that plasma adiponectin was increased with DNJ. Therefore, it was
      suggested that DNJ promoted an increase in plasma adiponectin and activated the
      beta-oxidation system. Overall, it was shown that DNJ prevents diet-induced
      obesity through an increase in adiponectin.

PMID- 23561073
TI  - Dummy-template molecularly imprinted solid phase extraction for selective
      analysis of ractopamine in pork.
AB  - Molecularly imprinted polymers (MIPs) for selective adsorption of ractopamine
      hydrochloride (RAC) were synthesised by an in situ method, in which salbutamol
      (SAL) was used as the dummy-template to avoid the template leakage. Scanning
      electron microscopy (SEM), mercury porosimerty and Fourier transform infrared
      spectroscopy (FTIR) were used to investigate the physical and morphological
      characteristics of the dummy-template MIPs. The test of adsorption selectivity
      indicated that the dummy-template MIPs exhibited high selectivity to RAC. The
      saturated adsorption capacity for RAC on dummy-template MIPs was 90.9 MUg g(-1).
      Based on the dummy-template polymers, a liquid chromatography-mass spectrometry
      (LC-MS) method was developed for the selective analysis of RAC in real pork
      samples. The averages of intra- and inter-day accuracy ranged from 78.9% to 92.2%
      and from 90.7% to 93.1%, respectively. The RSD% of repeatability ranged from 1.9%
      to 6.3%, and the RSD% of intermediate precision ranged from 3.5% to 9.2%, while
      the limit of detection (LOD) was 0.02 MUg kg(-1).

PMID- 23561074
TI  - Plums (Prunus domestica L.) are a good source of yeasts producing organic acids
      of industrial interest from glycerol.
AB  - The production of organic acids from several yeasts isolated from mature plums on
      media containing glycerol as carbon source was analysed by HPLC-UV. The yeasts
      isolated were identified by sequencing the 5.8S internal transcribed spacer as
      Pichia fermentans, Wickerhamomyces anomalus and Candida oleophila. The organic
      acid profiles of these strains comprise acetic, citric, succinic and malic acids
      that qualitatively and quantitatively vary between different species as well as
      among strains from the same species. The production from glycerol of succinic,
      acetic, citric, malic and oxalic acids from C. oleophila and W. anomalus, and
      that of succinic, oxalic and acetic acids by P. fermentans is reported for the
      first time in this work, as is the production of oxalic acid from glycerol in
      yeasts. Our results also showed that mature fruits can be a good source of new
      yeasts able to metabolise glycerol, producing different organic acids with
      industrial and biotechnological interest.

PMID- 23561075
TI  - Proanthocyanidin profile of cowpea (Vigna unguiculata) reveals catechin-O
      glucoside as the dominant compound.
AB  - Proanthocyanidin (PA) profile and content can have important nutritional and
      health implications on plant foods. Six diverse cowpea phenotypes (black, red,
      green, white, light-brown and golden-brown) were investigated for PA composition
      using normal-phase HPLC and reversed-phase UPLC-TQD-MS. Catechin and
      (epi)afzelechin were the major flavan-3-ol units. Unusual composition was
      observed in all cowpea phenotypes with significant degrees of glycosylation in
      the monomers and dimers. The PA content of cowpea (dry basis) ranged between 2.2
      and 6.3 mg/g. Monomeric flavan-3-ols were the largest group of PA (36-69%) in
      cowpea, with catechin-7-O-glucoside accounting for most (about 88%) of the
      monomers. The oligomers with degree of polymerization (DP) 2-4 ranged from 0.41
      to 1.3 mg/g (15-20%), whereas DP>10 polymers accounted for only 13.5% of PA.
      Future studies that highlight the impact of the unusual cowpea PA profile on
      nutritional and bioactive properties of this important legume are warranted.

PMID- 23561076
TI  - Blueberry estimated harvest from seven new cultivars: fruit and anthocyanins.
AB  - This study compares the yields, weights and anthocyanin contents of fruit from a
      group of seven new cultivars released from the New Zealand blueberry breeding
      programme and selected for the longest possible combined harvest season. The
      measured factors were primarily influenced by cultivar, and seasonal variations
      had relatively minor effects. The late-ripening cultivars 'Velluto Blue' and
      'Centra Blue' had the highest fruit yields, anthocyanin contents and estimated
      total anthocyanin harvestable from a given area. 'Blue Moon' and 'Sky Blue' had
      the largest fruit sizes. The early-ripening cultivars 'Blue Bayou', 'Blue Moon'
      and 'Sunset Blue' had the lowest anthocyanin contents. The yield, fruit size and
      total anthocyanin content results obtained from any single year were highly
      correlated with the average of the three years, which makes pursuing the
      evaluation for these traits from a single year and at an early stage of plant
      development a practical proposition.

PMID- 23561077
TI  - Active films based on cocoa extract with antioxidant, antimicrobial and
      biological applications.
AB  - Novel films of ethylene-vinyl alcohol copolymer (EVOH) containing flavonoid-rich
      cocoa were developed. To understand their potential application as active
      packaging material, antioxidant and antimicrobial properties of the films were
      determined as well as the antioxidant activity of the release compounds in Caco-2
      human epithelial colorectal adenocarcinoma cells. Exposure of the films to
      aqueous food simulant showed antioxidant capacity. The release of cocoa extract
      components was dependent on the antioxidant concentration incorporated in the
      film and on temperature. Cocoa extract and the fraction obtained after in vitro
      gastrointestinal digestion presented antioxidant activity against oxidative
      stress induced by hydrogen peroxide in Caco-2 cells. Films with 10%, 15%, and 20%
      cocoa extract produced bactericidal effect against Staphylococcus aureus,
      Listeria monocytogenes, Escherichia coli and Salmonella enterica. The application
      of films to an infant milk formula, previously inoculated with L. monocytogenes,
      inhibited the growth of bacteria 1.5 log units the first day and showed sustained
      release, inhibiting 0.52 and 0.76 log units, respectively, by the sixth day,
      while cocoa powder added directly did not produce any effect.

PMID- 23561078
TI  - In vivo and in vitro antioxidant activity and alpha-glucosidase, alpha-amylase
      inhibitory effects of flavonoids from Cichorium glandulosum seeds.
AB  - The aim of this study was to investigate the antioxidant, anti-glucosidase and
      anti-amylase activities of total flavonoids (TFs) from Cichorium glandulosum
      seeds, and to analyse its chemical composition by HPLC-ESI/MS. In vitro study,
      radical scavenging IC50 values of TFs were 7.33+/-0.093, 9.24+/-0.100, 154.33+/
      11.38 and 256.7+/-4.86 MUg/ml for DPPH, ABTS, hydroxyl radicals, and superoxide
      anion, respectively. In the 8-64 mg/ml range, alpha-glucosidase and alpha-amylase
      were inhibited by TFs to a certain extent. In vivo, the treatment groups with TFs
      (100, 200, 400 mg/kg) showed a significant decrease in the malondialdehyde level,
      the superoxide dismutase and glutathione levels were restored to almost normal
      levels, and the catalase and glutathione peroxidase levels significantly
      increased compared to the CCl4-intoxicated group in rats. The present study
      suggests that C. glandulosum seeds should be given special attention because of
      their antioxidant and anti-glucosidase, anti-amylase activity.

PMID- 23561079
TI  - Changes in selected parameters related to proteolysis during ageing of dry-cured
      pork loins inoculated with probiotics.
AB  - The effect of inoculation with a probiotic strain, Lactobacillus casei LOCK 0900,
      on selected parameters related to proteolysis of dry-cured pork loins during
      ageing was studied. Moisture content decreased significantly (p<0.05) throughout
      ageing, accompanied by a progressive reduction in water activity. The total
      nitrogen (TN) content increased during ageing with no effect (p<0.05) of
      inoculation with L. casei on its level. The greatest increase in non-protein
      nitrogen (NPN) content during ageing occurred in an inoculated sample,
      corresponding with the more pronounced decrease in pH. The intensity of
      proteolysis, as assessed by proteolysis index (PI), remained statistically
      significantly (p<0.05) unchanged during examined ageing periods. Inoculation with
      a probiotic strain does not significantly affect the degree of proteolysis in
      examined meat products after 21 and 28 days of ageing.

PMID- 23561080
TI  - Microencapsulation of aspartame by double emulsion followed by complex
      coacervation to provide protection and prolong sweetness.
AB  - The objective of this work was to microencapsulate aspartame by double emulsion
      followed by complex coacervation, aiming to protect it and control its release.
      Six treatments were prepared using sunflower oil to prepare the primary emulsion
      and gelatin and gum Arabic as the wall materials. The microcapsules were
      evaluated structurally with respect to their sorption isotherms and release into
      water (36 degrees C and 80 degrees C). The microcapsules were multinucleated, not
      very water-soluble or hygroscopic and showed reduced rates of equilibrium
      moisture content and release at both temperatures. FTIR confirmed complexation
      between the wall materials and the intact nature of aspartame. The results
      indicated it was possible to encapsulate aspartame with the techniques employed
      and that these protected the sweetener even at 80 degrees C. The reduced
      solubility and low release rates indicated the enormous potential of the vehicle
      developed in controlling the release of the aspartame into the food, thus
      prolonging its sweetness.

PMID- 23561082
TI  - Antioxidant activity-guided separation of coumarins and lignan from Melicope
      glabra (Rutaceae).
AB  - The ethyl acetate and methanol bark extracts of Melicope glabra were evaluated
      for their antioxidant capacities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free
      radical scavenging activity and beta-carotene bleaching/linoleic acid system.
      Both extracts exhibited strong inhibition against the DPPH radical (IC50 values
      of 24.81 and 13.01 MUg ml(-1), respectively) and strong antioxidant activity in
      beta-carotene bleaching assay. Both samples were found to have high phenolic
      content with values of 39 and 44 mg GAE/g as indicated by Follin-Ciocalteau's
      reagent. Antioxidant TLC assay-guided isolation on the methanol extract led to
      the isolation of a new pyranocoumarin, glabranin (1), umbelliferone (2),
      scopoletin (3) and sesamin (4), and their structures were determined by
      spectroscopy. Compounds (1-3) showed significant activities on DPPH free radical
      with the IC50 of 240.20, 810.02 and 413.19 MUg ml(-1), respectively. However, in
      beta-carotene bleaching assay, sesamin (4) showed higher inhibitory activity (1
      mg ml(-1), 95%) than glabranin (1) (1 mg ml(-1), 74%), whilst umbelliferone (2)
      and scopoletin (3) were slightly pro-oxidant.

PMID- 23561081
TI  - Enrichment of two isoflavone aglycones in black soymilk by using spent coffee
      grounds as an immobiliser for beta-glucosidase.
AB  - Spent coffee grounds, discarded as environmental pollutants, were adopted as
      enzyme immobilisation solid carriers instead of commercialised solid supports to
      establish an economical catalytic system. beta-Glucosidase was covalently
      immobilised onto spent coffee grounds for the conversion of isoflavone glycosides
      into their aglycones in black soymilk. Optimum conditions were determined to be
      40 degrees C and pH 6 using 4-nitrophenyl beta-D-glucuronide as an indicator.
      Operational reusability was confirmed for more than 30 batch reactions and the
      storage stability was capable of sustaining its highest catalytic activity for 20
      days. The kinetic parameters including rate constant (K), time (tau(50)) in which
      50% of isoflavone deglycosylation was reached, and time (tau(complete)) required
      to achieve complete isoflavone deglycosylation, were 0.16+/-0.02 min(-1), 4.54+/
      0.32 min, 60 min for daidzin and 0.16+/-0.02 min(-1), 2.28+/-0.11 min, 60 min for
      genistin, respectively. The total aglycone content in black soymilk was enriched
      by 67.14+/-0.60% in the enzymatic treatment of 60 min duration.

PMID- 23561083
TI  - Distribution, antioxidant and characterisation of phenolic compounds in soybeans,
      flaxseed and olives.
AB  - The distribution of free and bound phenolic compounds present in soybean,
      flaxseed and olive were investigated. The phenolic compounds were fractionated on
      the basis on their solubility characteristics in water, alcohol, dilute base and
      dilute acid. Reversed phase high pressure liquid chromatography (RP-HPLC) and
      mass spectrometry (MS) were used for identification of individual components of
      phenolic compounds. Antioxidant activity (AA%) of free and bound phenolic
      compounds was measured using the linoleic acid/beta-carotene assay. The water
      soluble phenolic compound fractions represented 68-81%, 50-72% and 46-56% of the
      total phenolic compounds measured in full-fat soybean, olive and flaxseed,
      respectively. Methanolic extraction of free phenolic compounds without heat,
      solubilised 21-56%, 42-62% and 34-51% of the total phenolic compounds measured in
      soybean, olive and flaxseed, respectively; methanol extraction of free phenolic
      compounds with heat solubilised a further 24-34%, 31-37% and 36-37% of phenolic
      compounds from soybean, olive and flaxseed, respectively. Further dilute alkali
      and dilute acid solubilised the remaining 10-40%, 1-21% and 12-29% of the total
      phenolic compounds from soybean, olive and flaxseed, respectively. Results
      indicated that the full-fat meals of soybean, flaxseed and olive showed higher
      antioxidant activity compared to defatted meals. RP-HPLC and LC-MS/MS profil1 for
      soybean, flaxseed and olive indicate two classes of phenolic compounds designated
      as free and bound phenolic compounds.

PMID- 23561084
TI  - Improved sample preparation and rapid UHPLC analysis of SO2 binding carbonyls in
      wine by derivatisation to 2,4-dinitrophenylhydrazine.
AB  - Sulphur dioxide (SO2) is essential for the preservation of wines. The presence of
      SO2 binding compounds in musts and wines may limit sulphite efficacy leading to
      higher total SO2 additions, which may exceed SO2 limits permitted by law and pose
      health risks for sensitive individuals. An improved method for the quantification
      of significant wine SO2 binding compounds is presented that applies a novel
      sample treatment approach and rapid UHPLC separation. Glucose, galacturonic acid,
      alpha-ketoglutarate, pyruvate, acetoin and acetaldehyde were derivatised with 2,4
      dinitrophenylhydrazine and separated using a solid core C18 phase by ultra high
      performance liquid chromatography. Addition of EDTA to samples prevented de novo
      acetaldehyde formation from ethanol oxidation. Optimised derivatisation duration
      enhanced reproducibility and allowed for glucose and galacturonic acid
      quantification. High glucose residues were found to interfere with the recovery
      of other SO2 binders, but practical SO2 concentrations and red wine pigments did
      not affect derivatisation efficiency. The calibration range, method accuracy,
      precision and limits of detection were found to be satisfactory for routine
      analysis of SO2 binders in wines. The current method represents a significant
      improvement in the comprehensive analysis of SO2 binding wine carbonyls. It
      allows for the quantification of major SO2 binders at practical analyte
      concentrations, and uses a simple sample treatment method that prevents treatment
      artifacts. Equipment utilisation could be reduced by rapid LC separation while
      maintaining analytical performance parameters. The improved method will be a
      valuable addition for the analysis of total SO2 binder pools in oenological
      samples.

PMID- 23561085
TI  - Free phenolics and polyphenol oxidase (PPO): the factors affecting post-cut
      browning in eggplant (Solanum melongena).
AB  - Polyphenol oxidase (PPO) catalyses oxidation of phenolics, which results in
      instant but differential browning in many cut fruits and vegetables, including
      eggplant. Eight cultivars of eggplant were characterised by their PPO specific
      activity, phenolic content, browning index, and PPO polymorphism. In fresh
      eggplant, browning was found to be dependent on both the phenolic content and PPO
      specific activity, whereas, total phenolic content played a major role in
      browning of stored fruits. Interestingly, although browning index increased in
      stored eggplant fruits, PPO activity reduced in four out of eight cultivars
      studied. Phenolic level was found to increase in all these cultivars during
      storage. Although a significant level of homology was observed in PPO nucleotide
      and conceptually translated protein sequence, two cultivars, which displayed
      highest PPO specific activity, differed in the 38 amino acid stretch in the
      peptide region 301-338.

PMID- 23561086
TI  - Synchronous two-dimensional MIR correlation spectroscopy (2D-COS) as a novel
      method for screening smoke tainted wine.
AB  - In this study, two-dimensional correlation spectroscopy (2D-COS) combined with
      mid-infrared (MIR) spectroscopy was evaluated as a novel technique for the
      identification of spectral regions associated with smoke-affected wine, for the
      purpose of screening taint arising from grapevine exposure to smoke. Smoke
      affected wines obtained from experimental and industry sources were analysed
      using MIR spectroscopy and chemometrics, and calibration models developed. 2D-COS
      analysis was used to generate synchronous data maps for red and white cask wines
      spiked with guaiacol, a marker of smoke taint. Correlations were observed at
      wavelengths that could be attributable to aromatic C-C stretching, i.e., between
      1400 and 1500 cm(-1), indicative of volatile phenols. These results demonstrate
      the potential of 2D-COS as a rapid, high-throughput technique for the preliminary
      screening of smoke tainted wine.

PMID- 23561087
TI  - Low resolution 1H NMR assignment of proton populations in pound cake and its
      polymeric ingredients.
AB  - Based on a model system approach, five different proton populations were
      distinguished in pound cake crumb using one dimensional low resolution (1)H NMR
      spectroscopy. In free induction decay (FID) measurements, proton populations were
      assigned to (i) non-exchanging CH protons of crystalline starch, proteins and
      crystalline fat and (ii) non-exchanging CH protons of amorphous starch and
      gluten, which are in little contact with water. In Carr-Purcell-Meiboom-Gill
      (CPMG) measurements, three proton populations were distinguished. The CPMG
      population with the lowest mobility and the FID population with the highest
      mobility represent the same proton population. The two CPMG proton populations
      with the highest mobility were assigned to exchanging protons (i.e., protons of
      water, starch, gluten, egg proteins and sugar) and protons of lipids (i.e.,
      protons of egg yolk lipids and amorphous lipid fraction of margarine)
      respectively. Based on their spin-lattice relaxation times (T1), two dimensional
      (1)H NMR spectroscopy further resolved the two proton populations with the
      highest mobility into three and two proton populations, respectively.

PMID- 23561088
TI  - Maqui berry (Aristotelia chilensis) and the constituent delphinidin glycoside
      inhibit photoreceptor cell death induced by visible light.
AB  - The protective effects of maqui berry (Aristotelia chilensis) extract (MBE) and
      its major anthocyanins [delphinidin 3,5-O-diglucoside (D3G5G) and delphinidin 3-O
      sambubioside-5-O-glucoside (D3S5G)] against light-induced murine photoreceptor
      cells (661W) death were evaluated. Viability of 661W after light treatment for 24
      h, assessed by the tetrazolium salt (WST-8) assay and Hoechst 33342 nuclear
      staining, was improved by addition of MBE, D3G5G, and D3S5G. Intracellular
      radical activation in 661W, evaluated using the reactive oxygen species (ROS)
      sensitive probe 5-(and-6)-chloromethyl-2,7-dichlorodihydro fluorescein diacetate
      acetyl ester (CM-H2DCFDA), was reduced by MBE and its anthocyanins. The anti
      apoptosis mechanism of MBE was evaluated by light-induced phosphorylation of p38.
      MBE significantly suppressed the light-induced phosphorylation of p38. These
      findings indicate that MBE and its anthocyanidins suppress the light-induced
      photoreceptor cell death by inhibiting ROS production, suggesting that the
      inhibition of phosphorylated-p38 may be involved in the underlying mechanism.

PMID- 23561089
TI  - The enhancement of antioxidant compounds extracted from Thymus vulgaris using
      enzymes and the effect of extracting solvent.
AB  - We evaluate the total phenolic compounds (TPC) content and the antioxidant
      activity (AA) of extracts obtained from ground fresh thyme (FT) and depleted
      thyme (DT), a by-product of the process of essential oil extraction. In addition,
      enzymatic treatments were evaluated to improve the extraction yields of
      polyphenolic compounds from thyme. Extractions were performed using several
      solvents as methanol, ethanol, and water. Enzymes were applied prior to
      extraction or during the extraction process. The best results were obtained using
      a mixture of methanol and water, resulting in 2790 and 220 mg Gallic acid
      equivalent (GAE)/L of TPC for FT and DT, respectively. A similar result was
      observed for AA. With regard to enzymatic treatment, application of Grindamyl CA
      150 enzyme as a pre-treatment resulted in the production of an extract from DT
      with 614 mg TE (trolox equivalent)/L of AA, 70% more than the control, and an AA
      of 621 mg TE/L (74% more than the control sample) was obtained using Grindamyl CA
      150 during the extraction process. These results suggest that enzymatic treatment
      is an interesting alternative for producing antioxidant extracts from DT.

PMID- 23561090
TI  - A single pump cycling-column-switching technique coupled with homemade high
      exchange capacity columns for the determination of iodate in iodized edible salt
      by ion chromatography with UV detection.
AB  - A single pump cycling-column-switching technique has been developed for the
      iodate analysis in edible salt. Homemade high exchange capacity columns were
      adopted for the separation of iodate and chloride. Iodate could be retained and
      concentrated in a homemade concentrator column after eluents passing through the
      suppressor. With UV detection, iodate exhibited satisfactory linearity in the
      range of 0.1-10.0 mg/L with a correlation coefficient of 0.9996. The detection
      limit (LOD) was 45.53 MUg/L, based on the signal-to-noise ratio of 3 (S/N=3) and
      a 100 MUL injection volume. Relative standard deviations (RSDs) for retention
      time, peak area and peak height were all less than 2.1%. Recoveries of added
      iodate were in the range of 98.4-101.6% for the spiked samples. The quantitative
      determination of iodate in edible salt was accomplished by this column-switching
      technique, without any pretreatment and interference. The results on six samples
      were statistically compared with results determined by conventional titrimetric
      method.

PMID- 23561091
TI  - Flavonoids from the capitula of Eriocaulon australe.
AB  - A flavan, eriocaulin A (1), and three flavone acyl glucosides, eriocaulosides A-C
      (2-4) were isolated from the capitula of Eriocaulon australe R. Br.
      (Eriocaulaceae), a Chinese medicine and an herb for health care beverages,
      together with seven known flavones and three isoflavones (5-14). The new
      flavonoids were elucidated as (2S)-3',4'-methylenedioxy-5-methoxy-7-hydroxyflavan
      (1), hispidulin 7-O-beta-D-(6-O-cinnamoyl)glucopyranoside (2), jaceosidin 7-O
      beta-D-(6-O-p-coumaroyl)glucopyranoside (3), jaceosidin 7-O-beta-D-(6-O-p
      hydroxybenzoyl)glucopyranoside (4) based on their spectroscopic data. All the 14
      flavonoids were obtained from this species for the first time. The in vitro
      cytotoxicity of compounds 1-14 against human lung adenocarcinoma A549, human
      breast adenocarcinoma MCF-7, and human cervical carcinoma HeLa cell lines was
      evaluated using the MTT colourimetric assay. Compounds 1, 7, and 9 were cytotoxic
      to A549, compounds 1, 2, 7, 9, 12, and 14 to MCF-7, and compounds 7, 9, and 14 to
      HeLa cells, with IC50 values ranging from 7.17 to 29.57 MUg/ml, while the others
      were inactive (IC50>50 MUg/ml).

PMID- 23561092
TI  - Characteristics of antioxidant activity and composition of pumpkin seed oils in
      12 cultivars.
AB  - The objective of this study was to determine the antioxidant properties, and
      provide characteristics, of the oil obtained from the seeds of 12 pumpkin
      varieties belonging to the species Cucurbita maxima Duch. and Cucurbita pepo L.
      Another objective was to establish which of the two extracting agents, ethanol or
      methanol, is more effective. The seeds of the pumpkin varieties examined differ
      in chemical composition and antioxidant activity. The seeds of the cultivars
      belonging to the species C. maxima are characterised by a higher content of fatty
      acids than are the cultivars of the species C. pepo. In the seed oil, unsaturated
      acids are dominant (oleic and linoleic), and their proportion depends on the
      pumpkin variety. The highest content of unsaturated acids has been measured in
      the oil extracted from the seeds of the cultivar, Jet F1 (C. pepo). Antioxidant
      activity analysis has produced the following findings. The seeds of the pumpkin
      varieties that belong to the species C. pepo exhibit better antioxidant
      properties, regardless of the extraction solvent used. 50% ethanol is more
      efficient than 80% methanol when used as an extracting agent. The antioxidant
      activity values obtained with 50% ethanol are higher than those achieved with 80%
      methanol. Owing to the considerable differences in composition among the fatty
      acids examined, it is possible to choose the desired pumpkin variety for the
      intended use.

PMID- 23561093
TI  - Influence of air-drying temperature on drying kinetics, colour, firmness and
      biochemical characteristics of Atlantic salmon (Salmo salar L.) fillets.
AB  - In this work the drying kinetics of Atlantic salmon (Salmo salar L.) fillets and
      the influence of air drying temperature on colour, firmness and biochemical
      characteristics were studied. Experiments were conducted at 40, 50 and 60 degrees
      C. Effective moisture diffusivity increased with temperature from 1.08*10(-10) to
      1.90*10(-10) m(2) s(-1). The colour difference, determined as DeltaE values (from
      9.3 to 19.3), as well as firmness (from 25 to 75 N mm(-1)) of dried samples
      increased with dehydration temperature. The lightness value L(*) and yellowness
      value b(*) indicated formation of browning products at higher drying
      temperatures, while redness value a(*) showed dependence on astaxanthin value.
      Compared with fresh fish samples, palmitic acid and tocopherol content decreased
      in a 20% and 40%, respectively, with temperature. While eicosapentaenoic acid
      (EPA) content remained unchanged and docosahexaenoic acid (DHA) content changed
      slightly. Anisidine and thiobarbituric acid values indicated the formation of
      secondary lipid oxidation products, which is more relevant for longer drying time
      than for higher drying temperatures.

PMID- 23561094
TI  - An integrated approach for flavour quality evaluation in muskmelon (Cucumis melo
      L. reticulatus group) during ripening.
AB  - Numerous and diverse physiological changes occur during fruit ripening and
      maturity at harvest is one of the key factors influencing the flavour quality of
      fruits. The effect of ripening on chemical composition, physical parameters and
      sensory perception of three muskmelon (Cucumis melo L. reticulatus group)
      cultivars was evaluated. Significant correlations emerging from this extensive
      data set are discussed in the context of identifying potential targets for melon
      sensory quality improvement. A portable ultra-fast gas-chromatograph coupled with
      a surface acoustic wave sensor (UFGC-SAW) was also used to monitor aroma volatile
      concentrations during fruit ripening and evaluated for its ability to predict the
      sensory perception of melon flavour. UFGC-SAW analysis allowed the discrimination
      of melon maturity stage based on six measured peaks, whose abundance was
      positively correlated to maturity-specific sensory attributes. Our findings
      suggest that this technology shows promise for future applications in rapid
      flavour quality evaluation.

PMID- 23561095
TI  - Studies of isothermal crystallisation kinetics of sunflower hard stearin-based
      confectionery fats.
AB  - The crystallisation and polymorphic properties of three sunflower hard stearins
      (SHSs) and cocoa butter equivalents (CBEs) formulated by blending SHSs and palm
      mid fraction (PMF) were studied and compared with those from cocoa butter (CB),
      to explore their possibilities as confectionery fats. The isothermal
      crystallisation kinetics of these fats were examined by pNMR and DSC at three
      different temperatures. All samples studied displayed a two-step crystallisation
      profile that could be fitted to an exponential-Gompertz equation. Stop-and-return
      DSC studies showed that SHSs and CBEs exhibited different crystallisation
      mechanisms according to their triacylglycerol composition, with a quick formation
      of metastable crystals, followed by a polymorphic transition to the more stable
      beta or beta' forms. X-ray diffraction (XRD) was used to investigate the
      polymorphic forms of tempered SHSs and CBEs in the long term. In all cases the
      resulting fats displayed short spacing patterns associated with beta
      polymorphism. These formulations based on SHSs and PMF met all the requirements
      to be considered as CBEs; therefore they could be used as an alternative to
      traditional confectionery fats.

PMID- 23561096
TI  - Simulated digestion of proanthocyanidins in grape skin and seed extracts and the
      effects of digestion on the angiotensin I-converting enzyme (ACE) inhibitory
      activity.
AB  - This study investigated the effect of in vitro gastrointestinal digestion on the
      stability and composition of flavan-3-ols from red grape skin and seed extracts
      (raw and purified, which are high in proanthocyanidins (PAs)). In addition, the
      effects of digestion on the angiotensin I-converting enzyme (ACE) inhibitory
      activities of these extracts were evaluated. The extracts were digested with a
      mixture of pepsin-HCl for 2 h, followed by a 2 h incubation with pancreatin and
      bile salts including a cellulose dialysis tubing (molecular weight cut-off 12
      kDa) at 37 degrees C with shaking in the dark and under N2. Under gastric
      conditions, the mean degree of polymerisation (mDP) of seed extracts, raw (mDP~6,
      p<0.05), and purified (mDP~10, p<0.05) was stable. The mDP of the raw skin
      extracts increased from 19 to 25 towards the end of the digestion. The PAs were
      significantly degraded (up to 80%) during the pancreatic digestion, yielding low
      molecular-weight compounds that diffused into the serum-available fraction
      (mDP~2). The overall mass transfer coefficient (K) of the seed extracts was 10(
      7) m(2)/s. After simulated gastrointestinal digestion, over 80% of ACE inhibition
      by raw seed and skin extracts was preserved. However, the purified seed and skin
      extracts lost their ability to inhibit ACE after intestinal digestion.

PMID- 23561097
TI  - Transport across Caco-2 monolayers of peptides arising from in vitro digestion of
      bovine milk proteins.
AB  - The entire panel of peptides produced from caseins (CN) and whey proteins (WP)
      that survive in vitro sequential gastro-pancreatic digestion and translocate
      across monolayers of Caco-2 cells, used as a model of the intestinal epithelium,
      has been characterised by HPLC and mass spectrometry. Among the milk-derived
      bioactive peptides, only minor amounts of mono-phosphorylated peptides arising
      from alphas1- and beta-CN were detected. The absorption behaviour of two
      resistant beta-lactoglobulin (beta-Lg) domains, beta-Lg 125-135 and beta-Lg 40
      60, was studied in detail using synthetic peptides. The IgE-binding properties of
      the digests recovered from the apical and basolateral monolayer compartments were
      evaluated by dot-blot, using the sera of milk allergic children (N=5). Outcomes
      indicated beta-Lg 127-135 as a possible "immune sensitising factor"in vivo. The
      almost complete loss of the IgE-affinity of CN and WP after digestion points out
      the need to design in vivo experiments to track the metabolic fate of dietary
      proteins.

PMID- 23561098
TI  - Purification and characterisation of sarcoplasmic calcium-binding protein, a
      novel allergen of red swamp crayfish (Procambarus clarkii).
AB  - Crayfish sarcoplasmic calcium-binding protein (SCP) was purified. The
      physicochemical and polymorphic characterisations were also analysed. SCP was
      purified by column chromatography to reveal a single band with molecular mass of
      22 kDa and further confirmed by mass spectrometry. The results of physicochemical
      characterisation showed that SCP was stable in the processes of thermal or
      acid/alkali treatment, and could be digested by simulate gastrointestinal fluid.
      Importantly, the comparison of SCP polymorphism using sera from crustacean
      allergic patients demonstrated SCP-II had a weaker IgE-binding activity. The
      isoelectric points of SCP subunits a, b and c were 4.6, 4.7, and 4.8,
      respectively, as determined by two-dimensional electrophoresis and IgE
      immunoblotting analysis showed that patients' sera reacted to three subunits of
      SCP. Finally, it can be concluded that SCP is a stable polymorphic allergen in
      crayfish, and all of its isotypes and subunits have allergenicity.

PMID- 23561099
TI  - Encapsulation of indole-3-carbinol and 3,3'-diindolylmethane in
      zein/carboxymethyl chitosan nanoparticles with controlled release property and
      improved stability.
AB  - Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are two bioactive
      compounds from Cruciferous vegetables. The stability of these compounds is a
      major challenge for their pharmaceutical applications. In this study, zein and
      zein/carboxymethyl chitosan (CMCS) nanoparticles were prepared to encapsulate I3C
      and DIM by a combined liquid-liquid phase separation and ionic gelation method.
      After zein nanoparticles were coated with CMCS, the zeta potential was decreased
      from around -10 to -20 mV, and encapsulation efficiency was greatly improved.
      Both nanoparticle formulations provided controlled release of I3C and DIM in PBS
      medium. Zein and zein/CMCS nanoparticles demonstrated similar protection for both
      I3C and DIM against ultraviolet (UV) light, attributed mainly to the contribution
      of the zein protein. Compared with zein nanoparticles, zein/CMCS nanoparticles
      exhibited better protection of I3C against degradation and better inhibition
      against its oligomerization to DIM under thermal condition (37 degrees C). Based
      on our results, the encapsulation of hydrophobic bioactives in zein/CMCS
      nanoparticles is a promising approach to improve their stability against harsh
      conditions and provide controlled release for food/pharmaceutical applications.

PMID- 23561100
TI  - Enzymatic modification enhances the protective activity of citrus flavonoids
      against alcohol-induced liver disease.
AB  - Alcoholic liver disease (ALD) can be developed by a prolonged or large intake of
      alcohol in a short period of time. ALD is considered as a leading cause for a
      liver injury in modern dietary life. This study was aimed to investigate the
      effects of orally administrated citrus flavonoids (CFs) and their enzymatically
      modified ones (EM-CFs) to prevent ALD. Hesperidin and narirutin were extracted
      from peels of Citrus unshiu by ultra-sonication and purified further. These CFs
      were modified enzymatically through glycosylation and de-rhamnosylation by the
      actions of cyclodextrin glucanotransferase (CGTase) and hesperidinase,
      respectively. CFs and EM-CFs were fed to ICR mouse along with ethanol for 8
      weeks, and changes in lipid contents, lipid peroxidation, GSH, antioxidant
      enzymes activity and proinflammatory cytokines in hepatic tissues were observed.
      Administration of CFs and EM-CFs along with alcohol significantly suppressed
      increases in prognostic parameters of a hepatocellular injury. Especially, EM-CFs
      fed groups maintained malondialdehyde, GSH levels and catalase activity in
      hepatic tissues close to those of the normal diet fed group. Abrupt increases in
      proinflammatory cytokines such as IkappaB-alpha, TNF-alpha, IL-1beta and IL-6 in
      hepatocytes due to a chronic alcohol uptake were significantly suppressed by co
      administration of EM-CFs. These results indicate that although the administration
      of CFs can alleviate ALD through preventing excessive lipid formation, protecting
      the antioxidant system and suppressing induction of inflammation in hepatocytes,
      their effectiveness can be further improved by glycosylation and de
      rhamnosylation.

PMID- 23561101
TI  - Analysis of irradiated cooked ham by direct introduction into the programmable
      temperature vaporizer of a multidimensional gas chromatography system.
AB  - A simple method involving direct introduction (DI) of cooked ham into a
      programmable temperature vaporizer and subsequent thermal desorption for
      multidimensional chromatographic analysis as a tool for studying changes of
      volatile compounds during food irradiation has been proposed. Analysis of non
      irradiated samples showed four peaks in the precolumn, which were identified on
      the main column as peak 1, ethyl acetate; peak 2, a mixture of octanol and ethyl
      propanoate; peak 3, (R,R)-2,3-butanediol, and peak 4, nonanoic acid. (R,R) and
      (S,S)-2,3-butanediol were detected in samples irradiated at 8 kGy, which may
      indicate that irradiation induces isomerisation. When a single cut was
      transferred from the precolumn to the main column, 1-tetradecene, n-pentadecane,
      8-heptadecene and 1-hexadecene were detected in irradiated samples. This simple
      and easy method allows detection of radiolytic markers and isomerisation of 2,3
      butanediol during irradiation of food.

PMID- 23561102
TI  - Carbon nanotubes-reinforced hollow fibre solid-phase microextraction coupled with
      high performance liquid chromatography for the determination of carbamate
      pesticides in apples.
AB  - An effective and sensitive method to determinate five carbamate pesticides in
      apples was developed by using carbon nanotubes-reinforced hollow fibre solid
      phase microextraction (CNTs-HF-SPME) combined with high performance liquid
      chromatography-photodiode array detection (HPLC-DAD). The CNTs were dispersed in
      water via adding surfactant, and then were held in the pores of HF supported by
      capillary forces and sonification. The SPME device, which was wetted with 1
      octanol, was placed in a stirred apple samples to extract target analytes. After
      extraction, analytes were desorbed and analyzed using HPLC-DAD. Under the
      optimized extraction conditions, the enrichment factors were achieved in the
      range from 49 to 308 with good inter-fibre repeatability and batch-to-batch
      reproducibility, while good linearity ranges and recoveries were obtained. The
      limits of detection ranged from 0.09 to 6.00 ng/g. Therefore, the results
      demonstrated that this novel method was an efficient pretreatment and enrichment
      procedure for the determination of trace carbamate pesticides in apples.

PMID- 23561103
TI  - Interlocking of beta-carotene in beta-lactoglobulin aggregates produced under
      high pressure.
AB  - Vitamin A deficiency is one of the major causes of mortality and morbidity in the
      developing World. This deficiency can be prevented by alimentary or
      pharmaceutical supplementation. However, both vitamin A oxidation and
      isomerization should be prevented, as these phenomenons result in loss of
      nutritional efficacy. The aim of this study was to investigate the effect of a
      food protein matrix, beta-lactoglobulin (beta-Lg) aggregates produced by high
      pressure (HP), on the stabilization of beta-carotene during storage and gastro
      duodenal digestion and therefore on its bioavailability. In vitro gastro-duodenal
      digestion of beta-Lg aggregates entrapping beta-carotene showed that up to 12%
      and 33% of total beta-carotene was released after peptic and pancreatic
      digestion, respectively. Overall, our study showed that beta-Lg aggregates are
      efficient for caging and stabilization of beta-carotene during storage and
      digestion. Hence, it may be an interesting approach for the protection and the
      delivery of vitamin A.

PMID- 23561104
TI  - Sonicated pineapple juice as substrate for L. casei cultivation for probiotic
      beverage development: process optimisation and product stability.
AB  - The aim of this study was to evaluate the use of sonicated pineapple juice as
      substrate for producing a probiotic beverage by Lactobacillus casei NRRL B442.
      Maximal microbial viability was found by cultivating L. casei at 31 degrees C and
      pH 5.8 (optimised conditions). After fermentation, samples of sweetened and non
      sweetened juice were stored. After 42 days of storage under refrigeration (4
      degrees C), the microbial viability was 6.03 Log CFU/mL in the non-sweetened
      sample and 4.77 Log CFU/mL in the sweetened sample. The pH of both samples
      decreased during storage due to lactic acid production (post acidification). The
      characteristic colour of the juice was maintained throughout the shelf life and
      no browning was observed. Sonicated pineapple juice was shown to be a suitable
      substrate for L. casei cultivation and for the development of an alternative non
      dairy probiotic beverage.

PMID- 23561105
TI  - Growth inhibition and antioxidative status induced by selenium-enriched broccoli
      extract and selenocompounds in DNA mismatch repair-deficient human colon cancer
      cells.
AB  - The effects of enzymatic-digested Se-enriched broccoli extracts (SeB) and
      selenocompounds on growth and antioxidative status in human colon cancer cells
      was investigated in this study. HCT116 and HCT116+Chr.3 cells were treated with
      selenocompounds (sodium selenite, sodium selenate, Se-Met, MeSeCys) or SeB [high
      Se (H-SeB) or low-Se (L-SeB)]. The cytotoxicity induced by selenocompounds in
      HCT116 cells was not associated with cellular H2O2 level, while the differential
      cytotoxicity observed by sodium selenite between HCT116 and HCT116+Chr.3 cell
      lines was related to cellular H2O2 production with the change in antioxidative
      enzyme activity, and the restoration of chromosome 3. H-SeB was found to reduce
      the cellular H2O2 content in HCT116+Chr.3 cells. The results in this study
      indicate that regardless of Se content, the cytotoxicity in HCT116 cells of both
      SeB forms appeared to be H2O2-independent, whereas the cytotoxicity in
      HCT116+Chr.3 of either SeB form appeared to be H2O2-dependent with an increase in
      antioxidative ability for H-SeB.

PMID- 23561106
TI  - A sensitive and selective imprinted solid phase extraction coupled to HPLC for
      simultaneous detection of trace quinoxaline-2-carboxylic acid and methyl-3
      quinoxaline-2-carboxylic acid in animal muscles.
AB  - A new molecularly imprinted polymer (MIP), selective for major metabolites of
      quinoxaline-1,4-dioxides, was prepared through bulk polymerisation using
      quinoxaline-2-carboxylic acid (QCA) as template, diethylaminoethylmethacrylate as
      functional monomer and ethylene glycol dimethacrylate as cross-linker in
      tetrahydrofuran. The synthesised MIP was characterised by Fourier transform
      infrared and adsorption experiments. MIP exhibited high affinity, fast kinetics
      for QCA and good selectivity for QCA and methyl-3-quinoxaline-2-carboxylic acid
      (MQCA). MIP obtained was used as a selective sorbent for molecularly imprinted
      solid phase extraction (MISPE) coupled with HPLC to detect QCA and MQCA. Under
      the optimal conditions, the limits of detection (S/N=3) of porcine, chicken and
      fish muscles were 0.1, 0.3, 0.1 MUg/kg for QCA and 0.2, 0.3, 0.1 MUg/kg for MQCA,
      respectively and good recoveries were obtained in the range from 60.0 to 119.4%.
      These results indicated the MISPE-HPLC procedure could be successfully used for
      the determination QCA and MQCA in animal muscles.

PMID- 23561107
TI  - Ligands affecting silver antimicrobial efficacy on Listeria monocytogenes and
      Salmonella enterica.
AB  - Although silver is being extensively used in food or other applications as the
      key component to control microbial proliferation, many factors affecting its real
      potential are still unknown. In the present work, the presence of specific
      ligands or the contents in organic matter was correlated with silver speciation
      and its antibacterial performance. Silver was found to be only active in form of
      free silver ions (FSI). The presence of chloride ions produced an equilibrium of
      stable silver chloride complexes which were void of antimicrobial efficacy.
      However, even at relatively high concentrations of chlorides, a small fraction of
      FSI may still be present, producing a bactericidal effect with concentrations at
      the nanomolar level under optimum conditions. Low concentrations of thiol groups
      completely inactivated silver, while methylsulphur groups only affected its
      efficacy at very high concentrations. Antibacterial performance revealed
      differences of about 1000-fold between results for environments with high organic
      matter content and results for aqueous salt buffers. Thiol groups were
      nonetheless not found directly associated with the decrease in antimicrobial
      performance in a nutrient rich environment. These results point out the
      complexity of the antimicrobial systems based on silver and can have relevance in
      food or other applications of silver as an antimicrobial.

PMID- 23561108
TI  - Antioxidant capacity, polyphenolic content and tandem HPLC-DAD-ESI/MS profiling
      of phenolic compounds from the South American berries Luma apiculata and L.
      chequen.
AB  - Native Myrtaceae fruits were gathered by South American Amerindians as a food
      source. At present, there is still some regional consume of the small berries
      from trees belonging to genus Luma that occurs in southern Chile and Argentina.
      The aerial parts and berries from Luma apiculata and Luma chequen were
      investigated for phenolic constituents and antioxidant capacity. A high
      performance electrospray ionisation mass spectrometry method was developed for
      the rapid identification of phenolics in polar extracts from both species. Thirty
      one phenolic compounds were detected and 27 were identified or tentatively
      characterised based on photodiode array UV-vis spectra (DAD), ESI-MS-MS
      spectrometric data and spiking experiments with authentic standards. Twelve
      phenolic compounds were detected in L. apiculata fruits and 12 in the aerial
      parts while L. chequen yielded 10 compounds in fruits and 16 in aerial parts,
      respectively. From the compounds occurring in both Luma species, seven were
      identified as tannins or their monomers, 15 were flavonol derivatives and five
      were anthocyanins. The whole berry and aerial parts extracts presented high
      antioxidant capacity in the DPPH assay (IC50 of 10.41+/-0.02 and 2.44+/-0.03
      MUg/mL for L. apiculata, 12.89+/-0.05 and 3.22+/-0.05 for L. chequen,
      respectively), which can be related to the diverse range of phenolics detected.
      The antioxidant capacity together with the high polyphenolic contents and
      compounds identified can support at least in part, their use as botanical drugs.
      From the compounds identified in both species, 3-O-(6"-O-galloyl)-hexose
      derivatives of myricetin, quercetin, laricitrin and isorhamnetin are reported for
      the first time for the genus Luma.

PMID- 23561109
TI  - Research on the preparation of antioxidant peptides derived from egg white with
      assisting of high-intensity pulsed electric field.
AB  - Egg white protein powder, one of the main egg products, was hydrolysed by
      Alcalase, Trypsin, and Pepsin respectively to prepare antioxidant peptides. All
      hydrolysates were assayed by determination of reducing power (RP) ability. Three
      kinds of hydrolysates were prepared under optimal enzymatic parameters that were
      obtained from the preliminary one-factor-at-a-time (OFAT) and response surface
      methodology (RSM) experiments. The results showed that the Alcalase hydrolysates
      exerted the best RP ability. Thereafter, the Alcalase hydrolysates were
      sequentially fractionated by ultra filtration membranes in cut-off molecular
      weight (MW) of 30, 10, and 1 kDa, and tested their antioxidant activities in
      terms of RP ability, DPPH radical scavenging ability, ABTS radical scavenging
      ability, and FRAP assay. Effects of high intensity pulsed electric field
      treatment were further investigated on antioxidant peptides to improve their
      activities. The results showed that Alcalase hydrolysates possessed the strongest
      antioxidant ability compared with the other two hydrolysates, particularly for
      the Fraction-3 with MW <1 kDa. After PEF treatment, this fraction showed a
      significant improvement of RP ability within 5 h (P<0.05).

PMID- 23561110
TI  - Systematic qualitative and quantitative assessment of anthocyanins, flavones and
      flavonols in the petals of 108 lotus (Nelumbo nucifera) cultivars.
AB  - Petal colour is one of the major characteristics that determine the ornamental
      value of lotus. To assess the contribution of different flavonoids to this
      character, composition and content of anthocyanins, flavones and flavonols were
      analysed through high performance liquid chromatography coupled with photodiode
      array detection tandem electrospray ionisation triple quad mass spectrometry in
      108 lotus cultivars with red, pink, yellow, white and red/white pied petal
      colours. Totally, five anthocyanins and fourteen flavones and flavonols were
      detected and quantified. In general, the yellow, white and pied species hardly
      contained any anthocyanins; red cultivars contain more than pink cultivars. Among
      the five anthocyanins, malvidin 3-O-glucoside was the most abundant one in all
      the cultivars that contain anthocyanin. The fourteen flavones and flavonols
      belonged to four groups based on their aglycones. Except for the yellow
      cultivars, kaempferol-derivatives were the most abundant one. These data might be
      helpful in lotus breeding for different colours.

PMID- 23561111
TI  - Structural characterisation of partially glycosylated whey protein as influenced
      by pH and heat using surface-enhanced Raman spectroscopy.
AB  - Maillard-induced glycosylation of whey protein improves solubility and thermal
      stability over a wide pH range. However, the relationship between structural
      changes and functional enhancement upon glycosylation is not well-characterized.
      Therefore, our objective was to characterise these structural changes and
      determine the protein conformation at various pH and thermal treatments, using
      surface-enhanced Raman-spectroscopy. The spectra of glycosylated protein revealed
      a new peak at 983 cm(-1) that can be used as a Raman marker for the early stage
      glycosylation. Upon glycosylation, structural variations were significant at the
      disulfide, hydrophobic, amide III, amide II, and amide I regions. Ionisation of
      carboxyl groups at all tested pH values, and increased beta-sheet configuration
      were also observed. The noted structural modifications imparted molecular
      rigidity and a consequent resistance to denaturation upon thermal treatment over
      a wide pH range. These findings can be used to explain various functional
      enhancements of whey protein upon glycosylation.

PMID- 23561112
TI  - Changes in urocanic acid, histamine, putrescine and cadaverine levels in Indian
      mackerel (Rastrelliger kanagurta) during storage at different temperatures.
AB  - Histamine, putrescine cadaverine and cis-urocanic acid (UCA) have all been
      implicated or suggested in scombroid fish poisoning. However, there is little
      information on UCA especially during storage. Changes in their contents during
      storage of whole Indian mackerel at 0, 3+/-1, 10+/-1 for up to 15 days and 23+/-2
      degrees C for up to 2 days were monitored. Fresh muscles contained 14.83 mg/kg
      trans-UCA, 2.23 mg/kg cis-UCA and 1.86 mg/kg cadaverine. Histamine and putrescine
      were not detected. After 15 days at 0 and 3 degrees C, trans-UCA content
      increased to 52.83 and 189.51 mg/kg, respectively, and decreased to <2 mg/kg at
      the other two temperatures. Storage at 10 degrees C also resulted in an increase
      in trans-UCA after 3 days, only to decrease after 6 days. The concentration of
      cis-UCA increased nearly 13-fold after 15 days at 0 and 3 degrees C, decreased at
      10 degrees C and remained unchanged at 23 degrees C. Histamine, putrescine and
      cadaverine levels increased significantly (P value<0.05) at all temperatures
      especially at 23 degrees C.

PMID- 23561113
TI  - Anticancer activity and mediation of apoptosis in human HL-60 leukaemia cells by
      edible sea cucumber (Holothuria edulis) extract.
AB  - Sea cucumbers have been a dietary delicacy and important ingredient in Asian
      traditional medicinal over many centuries. In this study, edible sea cucumber
      Holothuria edulis was evaluated for its in vitro anticancer potential. An aqueous
      fraction of the edible sea cucumber (ESC-AQ) has been shown to deliver a strong
      cytotoxic effect against the human HL-60 leukaemia cell line. An induction effect
      of apoptotic body formation in response to ESC-AQ treatment was confirmed in HL
      60 cells stained with Hoechst 33342 and confirmed via flow cytometry analysis.
      The up regulation of Bax and caspase-3 protein expression was observed while the
      expression of Bcl-xL protein was down regulated in ESC-AQ treated HL-60 cells.
      Due to the profound anticancer activity, ESC-AQ appears to be an economically
      important biomass fraction that can be exploited in numerous industrial
      applications as a source of functional ingredients.

PMID- 23561115
TI  - Influence of triterpenoids present in apple peel on inflammatory gene expression
      associated with inflammatory bowel disease (IBD).
AB  - Various ursanic, oleanic and lupanic pentacyclic triterpenoids found in apple
      peel were studied for anti-inflammatory effects in vitro using T84 colon
      carcinoma cells. After pretreatment with single triterpenoids, cells were
      stimulated with pro-inflammatory cytokines (TNF-alpha, INF-gamma, IL-1beta).
      Regulation of mRNA expression was analysed for three specific inflammation
      associated marker genes (TNF-alpha, IL-8, IP-10) using qRT-PCR. Furthermore, the
      effects of ursolic acid (UA) and oleanolic acid (OA) on the synthesis of certain
      pro-inflammatory proteins were examined. IP-10 expression was inhibited in a dose
      dependent manner by all the tested compounds at concentrations >=25 MUM. The mRNA
      expression of TNF-alpha was slightly affected and the IL-8 level was increased.
      At the protein level, UA and OA (25 MUM) reduced the synthesis of IP-10; sICAM-1,
      IL-23 and GROalpha were slightly repressed. The TNF-alpha level was not
      modulated, whereas induction of IL-8 was increased. UA also enhanced the
      synthesis of IL-1ra, while OA suppressed the level of I-TAC. The present study
      confirms that triterpenoids present in apple peel and beta-damascone may be
      implicated in the anti-inflammatory properties of apple constituents, suggesting
      that these substances might be helpful in the treatment of IBD as nutrient
      supplements.

PMID- 23561114
TI  - Synthesis of amino acid conjugates of tetrahydrocurcumin and evaluation of their
      antibacterial and anti-mutagenic properties.
AB  - Tetrahydrocurcumin (THC), the hydrogenated and stable form of curcumin, exhibits
      physiological and pharmacological activities similar to curcumin. A protocol has
      been developed for the synthesis of novel conjugates of THC with alanine (2a),
      isoleucine (2b), proline (2c), valine (2d), phenylalanine (2e), glycine (2f) and
      leucine (2g) in high yields (43-82%). All the derivatives of THC exhibited more
      potent anti-microbial activity than THC against Bacillus cereus, Staphylococcus
      aureus, Escherichia coli and Yersinia enterocolitica. The MIC values of the
      derivatives were 24-37% of those for THC in case of both gram-positive and gram
      negative bacteria. Derivatives 2g and 2d exhibited maximum anti-mutagenicity
      against Salmonella typhimurium TA 98 and TA 1538, respectively at a low
      concentration of 313 MUg/plate, with comparable activity for THC evident only at
      3750 MUg/plate. These results clearly demonstrated that the conjugation of THC at
      the phenolic position with amino acids led to significant improvement of its in
      vitro biological attributes.

PMID- 23561116
TI  - Comparison between gelatines extracted from mackerel and blue whiting bones after
      different pre-treatments.
AB  - Gelatines were extracted from mackerel and blue whiting bones after chemical or
      enzymatic pre-treatments and their functional properties (solubility, foaming and
      emulsifying properties) were analysed. The pre-treatment significantly (p<0.05)
      affected the composition and the functional properties of the extracted
      gelatines. The amino acid analyses showed that chemically pre-treated bone
      gelatines had higher imino acids (proline and hydroxyproline) contents compared
      to those extracted after the enzymatic pre-treatment, for both fish species. It
      was observed that all gelatines had higher solubility at low pH with a maximum
      value observed at pH 2. A significant effect of ionic strength was observed.
      Increasing the NaCl concentration to more than 1% resulted in a significant
      decrease of the solubility. Mackerel bone gelatines showed lower foaming capacity
      (FC) and higher foaming stability (FS) than blue whiting bone gelatines.
      Increasing the concentration of gelatine decreased the emulsifying activity index
      (EAI) but increased the stability index (ESI). The use of enzymes in the pre
      treatment process gave gelatines with significantly (p<0.05) higher EAI and ESI.

PMID- 23561117
TI  - Characteristics and antioxidant activity of water-soluble Maillard reaction
      products from interactions in a whey protein isolate and sugars system.
AB  - The objective of this study was to determine antioxidant activities of water
      soluble MRPs (Maillard reaction products) from the reactions between whey protein
      isolate (WPI) and xylose (X), glucose (G), fructose (F), lactose (L), maltose (M)
      and sucrose (S) at different initial pH values (3, 4, 5, 6, 7, 8 and 9). MRPs
      derived from the WPI-X system with increasing of pH rendered the highest
      browning, reducing power and DPPH radical-scavenging activity. SDS-PAGE analyses
      indicated formation of cross-linked proteins of large molecular mass produced
      from WPI-X systems. Results of FT-IR analysis indicated that the amide I, II and
      III bands of WPI from the WPI-X and WPI-G systems were changed by the Maillard
      reaction. CD spectroscopy showed that beta-sheet, beta-turns and random coil were
      increased while the alpha-helix was decreased after the WPI-G and WPI-X system
      aqueous solutions were heated. In conclusion, MRPs obtained from the WPI-X system
      had high antioxidant activity.

PMID- 23561118
TI  - Alternanthera paronychioides protects pancreatic beta-cells from glucotoxicity by
      its antioxidant, antiapoptotic and insulin secretagogue actions.
AB  - The antioxidant and antiglucotoxic effects of Alternanthera paronychioides on
      pancreatic beta-cell were investigated. Antioxidant assays demonstrated that
      ethanol extracts of A. paronychioides (EEAP) exhibited the highest antioxidant
      activity, which also had the highest phenolic and flavonoid contents. Two major
      polyphenolics, ferulic acid and quercetin, were identified from EEAP by HPLC-DAD.
      Effects of EEAP, ferulic acid and quercetin on high glucose (25 mmol/L)-induced
      pancreatic beta-cell apoptosis and dysfunction were further evaluated. Results
      showed that EEAP and quercetin but not ferulic acid protected beta-cells from
      glucotoxicity through several mechanisms, including: (1) maintaining beta-cell
      viability; (2) suppressing reactive oxygen species production; (3) reducing
      characteristic features of apoptosis; (4) inhibiting the activation of caspase-9
      and caspase-3 and the cleavage of poly (ADP-ribose) polymerase; (5) upregulating
      pancreatic and duodenal homeobox 1 gene expression and the insulin secretagogue
      action of pancreatic beta-cells. These findings may shed light on the preventive
      actions of A. paronychioides on diabetic glucotoxicity.

PMID- 23561119
TI  - Peach (Prunus persica) extract inhibits angiotensin II-induced signal
      transduction in vascular smooth muscle cells.
AB  - Angiotensin II (Ang II) is a vasoactive hormone that has been implicated in
      cardiovascular diseases. Here, the effect of peach, Prunus persica L. Batsch,
      pulp extract on Ang II-induced intracellular Ca(2+) mobilization, reactive oxygen
      species (ROS) production and signal transduction events in cultured vascular
      smooth muscle cells (VSMCs) was investigated. Pretreatment of peach ethyl acetate
      extract inhibited Ang II-induced intracellular Ca(2+) elevation in VSMCs.
      Furthermore, Ang II-induced ROS generation, essential for signal transduction
      events, was diminished by the peach ethyl acetate extract. The peach ethyl
      acetate extract also attenuated the Ang II-induced phosphorylation of epidermal
      growth factor receptor and myosin phosphatase target subunit 1, both of which are
      associated with atherosclerosis and hypertension. These results suggest that
      peach ethyl acetate extract may have clinical potential for preventing
      cardiovascular diseases by interfering with Ang II-induced intracellular Ca(2+)
      elevation, the generation of ROS, and then blocking signal transduction events.

PMID- 23561120
TI  - A new process for obtaining hydroxytyrosol using transformed Escherichia coli
      whole cells with phenol hydroxylase gene from Geobacillus thermoglucosidasius.
AB  - Phenol hydroxylase gene cloning from the thermophilic bacteria Geobacillus
      thermoglucosidasius was used to develop an effective method to convert tyrosol
      into the high-added-value compound hydroxytyrosol by hydroxylation. Phenol
      hydroxylase is a two-component enzyme encoded by pheA1 and pheA2 genes and
      strictly dependent on NADH and FAD. These two genes were subcloned together as a
      2 kb fragment into Escherichia coli Rosetta cells, and the transformants were
      able to grow and effectively transform up to 5 mM of phenol and tyrosol using
      IPTG (isopropyl-beta-D-thiogalactopyranoside) as inducer. In addition, when a new
      fragment with a 340 pb upstream pheA1 gene was subcloned, a similar
      biotransformation rate was attained without IPTG, confirming that this fragment
      encodes for a phenol hydroxylase promoter that can be recognised by E. coli. Both
      transformants brought about the total bioconversion of monophenols at a high
      concentration (5 mM), which represents an increase, both in concentration and in
      yield, compared with that previously described in the bibliography. The use of
      the transformant with its constitutive promoter was more interesting from a
      biotechnological point of view, since it is not necessary to use IPTG. It also
      gave rise to greater operational stability.

PMID- 23561121
TI  - MU-Calpain is involved in the postmortem proteolysis of gizzard smooth muscle.
AB  - Postmortem changes in proteins that have been implicated in affecting muscle
      integrity were examined in goose (GG) and duck (DG) gizzard smooth muscle stored
      at 5 degrees C. GG and DG smooth muscles were sampled at 0, 1, 3 and 7 day of
      storage. The pH was approximately 7 in both GG and DG samples during postmortem
      storage. Casein zymograms showed that 0-day MU-calpain activity was higher
      (p<0.05) in GG than in DG samples. As postmortem time progressed, MU-calpain was
      activated and autolyzed more extensively in GG than in DG samples. However, MU/m
      calpain remained relatively stable in both samples. Western blots indicated that
      postmortem desmin degradation was more rapid in GG than in DG samples. In
      contrast, alpha-actinin remained nearly unchanged in both samples. Therefore, our
      results suggest that MU-calpain has an important role in the postmortem
      proteolysis of gizzard smooth muscle.

PMID- 23561122
TI  - Migration and exposure assessment of silver from a PVC nanocomposite.
AB  - Nanotechnology is the manipulation of matter at the nanoscale, generally between
      1 and 100 nm. The discovery of unique nanomaterial properties has lead to novel
      applications in the food industry, one of which is antimicrobial food packaging
      materials. The objective of this study was to evaluate the migration of silver
      from plasticised polyvinyl chloride (PVC) nanocomposites to chicken meat
      following varying storage time and temperature conditions. The silver content of
      the chicken was quantified using inductively coupled plasma mass spectroscopy
      (ICPMS) and migration was found to occur within a range of 0.03-8.4 mg/kg. An
      exposure assessment revealed that human exposure to silver (assuming a worst case
      scenario that all silver is in its most harmful nanoform), is likely to be below
      current migration limits for conventional migrants and a provisional toxicity
      limit; however it is acknowledged there is still considerable uncertainty about
      the potential harmful effects of particles at the nanoscale. A sensitivity
      analysis revealed that silver migration from the nanocomposite to the food
      surface was influenced most by the percentage fill (p<0.01), followed by storage
      time (p<0.01) and storage temperature (p<0.05). This study represents an initial
      and much needed attempt to quantify human risks from the use of nanomaterials in
      the food industry.

PMID- 23561123
TI  - Free fatty acid profiles of emulsified lipids during in vitro digestion with
      pancreatic lipase.
AB  - Individual free fatty acids released from milk protein-stabilized emulsions
      prepared with milk fat, soya bean oil or tuna fish oil during in vitro digestion
      with pancreatic lipase were monitored using gas chromatography. The results
      showed that saturated fatty acids (C16:0 and C18:0) were released faster than
      unsaturated fatty acids (C18:1n9, C18:2n6 and C18:3n3) from soya bean oil
      emulsions; short chain fatty acids were released faster than long chain fatty
      acids from milk fat emulsions; long chain polyunsaturated fatty acids, such as
      eicosapentaenoic acid and docosahexaenoic acid, were released more slowly than
      other fatty acids from fish oil emulsions. The results confirm that the release
      behaviour of fatty acids from emulsions during digestion is related not only to
      the position of the fatty acids in the triglycerides in the fat/oil, but also to
      the length of the carbon chain of the fatty acid. The rates and the extents of
      the digestion of lipids consisting of short chain fatty acids are higher than
      those of lipids consisting of long chain fatty acids.

PMID- 23561124
TI  - Comparison of biogenic amine and polyphenol profiles of grape berries and wines
      obtained following conventional, organic and biodynamic agricultural and
      oenological practices.
AB  - The bio-active compounds present in food and beverages have a high potential
      influence on the future health of humans. The levels of biogenic amines,
      anthocyanins, polyphenols and antioxidant activity were measured in white
      (Pignoletto) and red (Sangiovese) grape berries and wines from the Emilia-Romagna
      region (Italy) obtained following conventional, organic and biodynamic
      agricultural and oenological practices. No significant difference was shown among
      the samples coming from different agricultural and winemaking practices.
      Principal Component Analysis was also performed. Biogenic amine amounts were
      higher in red than in white berries, while in the wines an opposite trend was
      observed, with histamine, tyramine and putrescine being the most abundant in
      Pignoletto wines. Red grapes and wines were richer in anthocyanins and showed
      higher antioxidant activity than white ones. The total level of polyphenols was
      similar in red and white berries, but with different metabolite profiles
      depending on the grape variety.

PMID- 23561125
TI  - Characterisation of muscles from Frigate mackerel (Auxis thazard) and catfish
      (Clarias macrocephalus).
AB  - Frigate mackerel (Auxis thazard) and catfish (Clarias macrocephalus) can be used
      as alternative sources for surimi production. However, the functionality of
      surimi is species-dependent. This study aimed to characterise certain chemical
      and physical compositions of dark and ordinary muscles from these species.
      Catfish, particularly ordinary muscle, was composed of higher contents of lipid
      and carotenoid than Frigate mackerel muscle (p<0.05) but ordinary muscle from
      Frigate mackerel had the highest phospholipid content (p<0.05). Both dark and
      ordinary muscles of Frigate mackerel had greater contents of myofibrillar
      proteins than had catfish muscle (p<0.05). Myosin heavy chain and actin were
      predominant proteins found in both muscle types of both species. Dark muscle from
      Frigate mackerel had the highest sarcoplasmic protein content, especially
      extractable myoglobin (p<0.05). Muscles from Frigate mackerel had greater content
      of sodium chloride than had catfish (p<0.05). The highest contents of iron,
      copper and selenium were found in Frigate mackerel dark muscle (p<0.05). The pH
      of ordinary muscle from both species was higher than that of dark muscle
      (p<0.05). Frigate mackerel, especilly dark muscle, exhibited the most dark-red
      colour, as shown by the lowest L(*) and b(*) values with the highest a(*) value
      and redness index (a(*)/b(*)) (p<0.05).

PMID- 23561126
TI  - Fundamental studies on the structural functionality of whey protein isolate in
      the presence of small polyhydroxyl compounds as co-solute.
AB  - The present work deals with the changing network morphology of whey protein
      isolate (15%, w/w) in the presence of glucose syrup (co-solute) with
      concentrations ranging from 0% to 65% (w/w) in 10 mM CaCl2 solution, thus
      producing formulations with a total level of solids of up to 80% (w/w).
      Denaturation behaviour and aggregation of whey protein systems were investigated
      using small deformation dynamic oscillation on shear, micro and modulated
      differential scanning calorimetry, and confocal laser scanning microscopy. A
      progression in the mechanical strength of protein aggregates was observed
      resulting from enhanced protein-protein interactions in the presence of glucose
      syrup. Addition of the co-solute resulted in better thermal stability of protein
      molecules by shifting the process of denaturation to higher temperature, as
      observed by calorimetry. Observations are supported by micrographs showing
      coherent networks with reduced size of whey protein aggregates in the presence of
      high levels of glucose syrup, as opposed to thick and random clusters for systems
      of whey protein by itself. Glass transition phenomenon was observed for condensed
      protein/co-solute systems, which were treated with theoretical concepts adapted
      from synthetic polymer research to pinpoint the mechanical glass transition
      temperature.

PMID- 23561127
TI  - In vitro antioxidant capacity and anti-inflammatory activity of seven common
      oats.
AB  - Oats are gaining increasing scientific and public interest for their purported
      antioxidant-associated health benefits. Most reported studies focused on specific
      oat extracts or particular oat components, such as beta-glucans, tocols (vitamin
      E), or avenanthramides. Studies on whole oats with respect to antioxidant and
      anti-inflammatory activities are still lacking. Here the antioxidant and anti
      inflammatory activities from whole oat groats of seven common varieties were
      evaluated. All oat varieties had very similar oxygen radical absorption capacity
      compared with other whole grains. In an anti-inflammatory assay, oat variety CDC
      Dancer inhibited tumor necrosis factor-alpha induced nuclear factor-kappa B
      activation by 27.5% at 2 mg/ml, whereas variety Deiter showed 13.7% inhibition at
      a comparable dose. Avenanthramide levels did not correlate with the observed
      antioxidant and anti-inflammatory activities. Further investigations are needed
      to pinpoint the specific antioxidant and anti-inflammatory compounds, and
      potential synergistic and/or matrix effects that may help explain the mechanisms
      of oat's anti-inflammatory actions.

PMID- 23561128
TI  - Effect of nitrite on the odourant volatile fraction of cooked ham.
AB  - The aim of this work was to reliably identify the key odour compounds in cooked
      ham and acquire new knowledge on the role of sodium nitrite on the formation of
      its aroma. Gas chromatography coupled with mass spectrometry and (or)
      olfactometry was used. In all, 24 odourants were identified in the volatile
      fraction of cooked ham. Their main origins are discussed. Orthonasal sniffing of
      the hams was used to study how these substances contributed to the overall aroma
      of the product. The aroma of cooked ham is a balance between that of certain
      sulfur compounds produced during cooking and that of oxidation compounds commonly
      found in cooked meats. In the absence of nitrite, this balance is disturbed by
      extensive formation of oxidation compounds that mask the meaty notes induced by
      the sulfur compounds.

PMID- 23561129
TI  - Croton lechleri Mull. Arg. (Euphorbiaceae) stem bark essential oil as possible
      mutagen-protective food ingredient against heterocyclic amines from cooked food.
AB  - The Amazonian Croton lechleri stem bark essential oil was tested for its anti
      mutagenic potential by performing the Ames test against heterocyclic amines
      (HCAs), in continuing research on applicative functional profile of this
      phytocomplex as food ingredient (Rossi et al., 2011). Salmonella typhimurium
      strain TA98 was used with and without metabolic activation (S9 mix). The anti
      mutagenic properties was assayed with the following HCAs: 2-amino-3-methylimidazo
      [4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo-[4,5-f]quinoline (MeIQ), 2
      amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx), the imidazoles 2-amino-6
      methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipirydo-[1,2
      a:3',2'-d]imidazole (Glu-P-2). All HCAs with S9 induced mutagenicity at 10(-10)
      mol/plate. Without S9, IQ and MeIQ showed mutagenicity at 10(-8) mol/plate, MeIQx
      and Glu-P-1 at 10(-5) mol/plate, while Glu-P-2 was inactive. In presence of HACs
      (10(-9) mol/plate), C. lechleri essential oil was tested for mutagen-protective
      properties (concentration range: 0.01-0.10 mg/plate) taking the Highest
      Uneffective Dose (HUD) as threshold reference. With S9 mix, C. lechleri essential
      oil displayed a significant reduction of revertants at 0.05 mg/plate, from 21% to
      34%. The essential oil showed mutagen-protective efficacy against IQ and MeIQ
      tested as direct mutagens (10(-7) mol/plate), with a revertants percentage
      reduction of 39% and 40%, respectively. No anti-mutagen capacity was noted for
      MeIQx and Glu-P-1 (10(-5) mol/plate). Since HACs are known as possible colon and
      liver cancer inducers, C. lechleri essential oil was tested for its cytotoxicity
      and anti-proliferative capacity against LoVo and HepG2 cancer cell lines showing
      IC50 of 74.95+/-0.05 MUg/ml (LoVo) and 82.28+/-0.03 MUg/ml (HepG2), displaying a
      promising role of this essential oil as a functional food ingredient with
      interesting mutagen preventing properties.

PMID- 23561130
TI  - Microcapsule production employing chickpea or lentil protein isolates and
      maltodextrin: physicochemical properties and oxidative protection of encapsulated
      flaxseed oil.
AB  - Flaxseed oil was microencapsulated, employing a wall material matrix of either
      chickpea (CPI) or lentil protein isolate (LPI) and maltodextrin, followed by
      freeze-drying. Effects of oil concentration (5.3-21.0%), protein source (CPI vs.
      LPI) and maltodextrin type (DE 9 and 18) and concentration (25.0-40.7%), on both
      the physicochemical characteristics and microstructure of the microcapsules, were
      investigated. It was found that an increase in emulsion oil concentration
      resulted in a concomitant increase in oil droplet diameter and microcapsule
      surface oil content, and a decrease in oil encapsulation efficiency. Optimum
      flaxseed oil encapsulation efficiency (~83.5%), minimum surface oil content
      (~2.8%) and acceptable mean droplet diameter (3.0 MUm) were afforded with 35.5%
      maltodextrin-DE 9 and 10.5% oil. Microcapsules, formed by employing these
      experimental conditions, showed a protective effect against oxidation versus free
      oil over a storage period of 25 d at room temperature.

PMID- 23561132
TI  - Characterisation of non-polar dimers formed during thermo-oxidative degradation
      of beta-sitosterol.
AB  - Thermo-oxidative degradation of sterols at temperature typical for frying leads
      to the formation of oxidised derivatives, fragmented sterols and oligomers.
      Recent research on sterol oxidation focuses mainly on the oxysterol derivatives
      formation to the exclusion of compounds with high molecular mass. The aim of this
      work was to decipher the chemical structure of non-polar dimers formed during
      beta-sitosterol oxidation at 180 degrees C in the presence of oxygen. The dimer
      fraction was separated by size-exclusion chromatography (SEC) after pre
      fractionation on silica gel. The chemical structure of the dimers was assessed by
      1D and 2D NMR, IR, Raman and MS spectroscopies. NMR data confirmed that the
      predominant non-polar dimer formed during beta-sitosterol oxidative degradation
      has a configuration of 3beta,3beta'-disitosteryl ether. Data from IR and Raman
      spectroscopies further proved it chemical structure. Applied analytical
      techniques also confirmed presence of dimers with different configuration than
      disteryl ethers.

PMID- 23561131
TI  - Isolation of new monoterpene coumarins from Micromelum minutum leaves and their
      cytotoxic activity against Leishmania major and cancer cells.
AB  - On the basis of a leishmanicidal assay-guided isolation, two new monoterpene
      coumarins, minutin A and minutin B, were purified from Micromelum minutum leaves
      together with four known coumarins, 8,4"-dihydroxy-3",4"-dihydrocapnolactone
      2',3'-diol, 8-hydroxyisocapnolactone-2',3'-diol, 8-hydroxy-3",4"
      dihydrocapnolactone-2',3'-diol, and clauslactone E. Among these compounds,
      minutin A, minutin B, 8-hydroxyisocapnolactone-2',3'-diol and clauslactone E
      showed a significant cytotoxic activity against Leishmania major with IC50 values
      of 26.2, 20.2, 12.1, and 9.8 MUM, respectively, while 8,4"-dihydroxy-3"4"
      dihydrocapnolactone-2',3'-diol and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol
      were not active. However, all these compounds exhibited some inhibitory activity
      against one or more lung adenocarcinoma (SBC3 and A549) and leukaemia (K562, and
      K562/ADM) cell lines. Amongst these, clauslactone E, minutin B and 8
      hydroxyisocapnolactone-2',3'-diol possessed the strongest cytotoxic activity
      against SBC3, A549, K562, and K562/ADM cell lines, with IC50 values of 3.7, 10.4,
      12.1, and 10.8 MUM for clauslactone E; 9.6, 17.5, 8.7 and 6.7 MUM for minutin B;
      8.8, 10.1, 16.9, and 10.1 MUM for 8-hydroxyisocapnolactone-2',3'-diol,
      respectively.

PMID- 23561133
TI  - Immobilisation of beta-cyclodextrin on glass: characterisation and application
      for cholesterol reduction from milk.
AB  - beta-Cyclodextrin (beta-CD) was converted into beta-CD-N3 by chemical
      modification and subsequently attached covalently on glass surface by click
      reaction. Functionalised glass surface was characterised by static water contact
      angle and X-ray photoelectron spectroscopy (XPS). Both techniques show that beta
      CD was successfully attached on glass surface. beta-CD on solid surface was used
      to make a complexation with cholesterol to remove it from milk. 69+/-1%
      cholesterol was reduced in 4 h at 25 degrees C and 170 rpm. The same surface was
      used repeatedly for eight cycles and it maintained its efficiency, with 68+/-2%
      cholesterol reduction. Modified glass surface showed almost no degradation as
      confirmed from XPS analysis after eight cycles of repeated use in cholesterol
      reduction experiments. The high efficiency and stability of functional monolayer
      was attributed to its specific structure with relatively low number of functional
      groups and longer spacer chain length to providing higher flexibility to beta-CD
      molecules.

PMID- 23561134
TI  - Pesticide residues determination in Polish organic crops in 2007-2010 applying
      gas chromatography-tandem quadrupole mass spectrometry.
AB  - A sensitive, accurate and reliable multiresidue method based on the application
      of gas chromatography-tandem quadrupole mass spectrometry (GC-QqQ-MS/MS) has been
      established for screening, identification and quantification of a large number of
      pesticide residues in produce. The method was accredited in compliance with PN-EN
      ISO/IEC 17025:2005 standard and it was operated under flexible scope as PB-11
      method. The flexible scope of accreditation allowed for minor modifications and
      extension of the analytical scope while using the same analytical technique.
      During the years 2007-2010, the method was used for the purpose of verification
      of organic crop production by multiresidue analysis for the presence of
      pesticides. A total of 528 samples of differing matrices such as fruits,
      vegetables, cereals, plant leaves and other green parts were analysed, of which
      4.4% samples contained pesticide residues above the threshold value of 0.01
      mg/kg. A total of 20 different pesticide residues were determined in the samples.

PMID- 23561135
TI  - 4-Methyl-7-hydroxycoumarin antifungal and antioxidant activity enhancement by
      substitution with thiosemicarbazide and thiazolidinone moieties.
AB  - According to literature data, thiosemicarbazide and thiazolidinone moieties
      should enhance biological properties of coumarin. Antioxidant, metal-chelating
      and antifungal activities of all compounds were investigated and compared to the
      activity of the starting material, 7-hydroxy-4-methylcoumarin, and were proven to
      possess potent antioxidant and antifungal activity. In general,
      thiosemicarbazides showed higher scavenging activity towards DPPH and galvinoxyl
      radicals than did 4-thiazolidinones and some of them had the same or even better
      activity than had ascorbic acid itself, depending on the free radical used. In
      antifungal activity tests towards four foodborne mycotoxigenic fungi, Aspergillus
      flavus, Aspergillus ochraceus. Fusarium graminearum and Fusarium verticillioides,
      coumarin derivatives were proven to possess a very high activity in terms of
      growth inhibition, depending on the fungi investigated. In general, 4
      thiazolidinones showed better antifungal activity than did thiosemicarbazides. F.
      graminearum was the most susceptible to the compounds investigated and F.
      verticillioides was proven to be the most resistant. Two compounds, both
      coumarinyl thiosemicarbazides, were found to possess both antifungal and
      antioxidant activity which could be useful for applications in medicine, food
      industry and agriculture.

PMID- 23561136
TI  - Assay of phenolic compounds from four species of ber (Ziziphus mauritiana L.)
      fruits: comparison of three base hydrolysis procedure for quantification of total
      phenolic acids.
AB  - The present study was undertaken to investigate the flavonoid profile in four
      species of ber (Ziziphus mauritiana Lamk.) fruit. The 12 flavonoids identified
      were quercetin 3-O-robinobioside, quercetin 3-O-rutinoside, quercetin 3'-O
      galactoside, quercetin 3'-O-glucoside, quercetin 3'-O-rhamnoside, quercetin 3'-O
      pentosylhexoside, quercetin 3-O-6'malonylglucoside, quercetin 3'-O
      malonylglucoside, luteolin 7-O-6'malonylglucoside, luteolin 7-O-malonylglucoside,
      myricetin 3-O-galactoside, and naringenin tri glycoside. This is the first report
      on extraction of nine additional flavonoids from the ber fruits. In addition, we
      also compared the impact of three different base hydrolysis techniques namely
      ultrasonic assisted base hydrolysis (UABH), microwave assisted base hydrolysis
      (MWABH), and pressurised liquid assisted base hydrolysis (PLABH) for the
      quantification of total phenolic acids. Nine phenolic acids, protocatechuic acid,
      p-hydroxybenzoic acid, ferulic acid, chlorogenic acid, vanillic acid, caffeic
      acid, vanillin, ortho- and para-coumaric acids, were identified and quantified.
      The three major phenolic acids identified in all four ber species were p-coumaric
      acid, vanillin and ferulic acids. Higher amounts (p<0.05) of total phenolic acids
      in all cultivars were obtained with the PLABH technique as compared to other two
      procedures (UABH and MWABH).

PMID- 23561137
TI  - Anti-inflammatory and anticancer activities of extracts and compounds from the
      mushroom Inonotus obliquus.
AB  - Mushroom Inonotus obliquus (I. obliquus) has been used as functional food and
      traditional Chinese herbs for long time. An efficient method for bioassay-guided
      preparative isolation was used for identifying the anti-inflammatory and
      anticancer constituents in I. obliquus. The petroleum ether and ethyl acetate
      fractions were found to have significant inhibition effects on NO production and
      NF-kappaB luciferase activity in macrophage RAW 264.7 cells and cytotoxicity
      against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA-MB-231.
      Six main constituents were isolated from these two fractions and they were
      identified as lanosterol (1), 3beta-hydroxy-8,24-dien-21-al (2), ergosterol (3),
      inotodiol (4), ergosterol peroxide (5) and trametenolic acid (6). Compound
      ergosterol, ergosterol peroxide and trametenolic acid showed anti-inflammatory
      activities and ergosterol peroxide and trametenolic acid showed obviously
      cytotoxicity on human prostatic carcinoma cell PC3 and breast carcinoma MDA-MB
      231 cell. The results obtained in this work might contribute to understanding the
      biological activity of mushroom I. obliquus for food and drug application.

PMID- 23561138
TI  - Enzyme-assisted extraction of bioactive compounds from ginger (Zingiber
      officinale Roscoe).
AB  - Ginger (Zingiber officinale R.) is a popular spice used in various foods and
      beverages. 6-Gingerol is the major bioactive constituent responsible for the
      antiinflammatory, antitumour and antioxidant activities of ginger. The effect of
      application of alpha-amylase, viscozyme, cellulase, protease and pectinase
      enzymes to ginger on the oleoresin yield and 6-gingerol content has been
      investigated. Pre-treatment of ginger with alpha-amylase or viscozyme followed by
      extraction with acetone afforded higher yield of oleoresin (20%+/-0.5) and
      gingerol (12.2%+/-0.4) compared to control (15%+/-0.6 oleoresin, 6.4%+/-0.4
      gingerol). Extraction of ginger pre-treated with enzymes followed by extraction
      with ethanol provided higher yield of gingerol (6.2-6.3%) than the control (5.5%)
      with comparable yields of the oleoresin (31-32%). Also, ethanol extract of
      cellulase pre-treated ginger had the maximum polyphenol content (37.5 mg/g).
      Apart from 6-gingerol, 6-paradol along with 6- and 8-methyl shogaols were the
      other important bio-active constituents in the oleoresin from cellulase-treated
      ginger.

PMID- 23561139
TI  - Chemical profile and sensory properties of different foods cooked by a new
      radiofrequency oven.
AB  - Radio frequency (RF) heating has been used for numerous applications in the food
      industry such as baking, thawing or pasteurisation. It reduces cooking time, and
      it helps to retain acceptable food colour and texture. In this paper, chemical
      and sensory data obtained from broccoli, potatoes, salmon and cocoa cakes cooked
      using an innovative RF oven were reported. The oven has an algorithm able to
      monitor the energy feedback from the cavity and to adjust the energy output
      accordingly. The different foods were cooked to the same end point and the
      concentration of phytochemicals, vitamins and acrylamide were assessed. Results
      demonstrated that RF oven preserved ascorbic acid and increased glucosinolates
      concentration in broccoli and it decreased the formation of acrylamide in roasted
      potatoes more than 50%. The total amount of vitamins B was 30% and 50% higher in
      RF cooked salmon than conventionally cooked salmon prepared at 55 and 75 degrees
      C, respectively.

PMID- 23561140
TI  - Changes in polyphenol content during production of grape juice concentrate.
AB  - The production of grape juice concentrate on an industrial scale was evaluated
      and samples from the main steps of processing have been collected and analyzed.
      The sampling steps included the selection and washing of grapes (Nevsehir Patlak
      variety), pressing in order to obtain the juice separate from the seed and the
      skin fraction, pasteurization, clarification, filtration, evaporation, and
      filling-packing at 27 degrees C with a Brix of 45 degrees . Samples from each of
      the processing steps were analyzed by a number of spectrophotometric analyses. A
      series of anthocyanin compounds was identified using HPLC-MS, and the fate of
      anthocyanins, quercetin rutinoside and procyanidins was followed using HPLC. The
      results indicate that the removal of seed and fruit skin removes most of the
      procyanidins and anthocyanins, while subsequent clarification and filtration
      treatments further reduce the anthocyanin content.

PMID- 23561141
TI  - Chemical stability of astaxanthin nanodispersions in orange juice and skimmed
      milk as model food systems.
AB  - Solubilising astaxanthin in nanodispersion systems is a promising approach to
      incorporate astaxanthin into water-based food formulations. In this research, the
      chemical stabilities of astaxanthin nanodispersions diluted in orange juice and
      skimmed milk as model food systems and in deionised water as a control were
      evaluated. The nanodispersions displayed significantly (p<0.05) better stability
      in food systems compared to the control. The effects of stabilisers and dilution
      factor were also studied. In skimmed milk and deionised water, the type of
      stabiliser had a significant effect (p<0.05) on astaxanthin degradation during
      storage. In vitro cellular uptake of astaxanthin from diluted astaxanthin
      nanodispersions in selected food systems was also evaluated. The cellular uptake
      of astaxanthin nanodispersions in skimmed milk was significantly higher (p<0.05)
      than that of astaxanthin nanodispersions in orange juice and deionised water.
      High in vitro cellular uptake of astaxanthin from the prepared astaxanthin
      nanodispersions can be achieved via incorporation into protein-based foods such
      as milk.

PMID- 23561142
TI  - Physico-chemical characteristics and sensory evaluation of wheat bread partially
      substituted with banana (Musa acuminata X balbisiana cv. Awak) pseudo-stem flour.
AB  - The physico-chemical and sensorial properties of the control (BCtr), commercial
      wheat flour (CWF) bread substituted with 10% BPF (banana pseudo-stem flour)
      (B10BPF) and B10BPF with added 0.8% w/w (flour weight basis) xanthan gum (XG) or
      sodium carboxymethylcellulose (CMC) (B10BPFXG and B10BPFCMC, respectively) were
      examined. The proximate analyses revealed that the composite bread had
      significantly higher moisture, ash, crude fibre, soluble, insoluble and total
      dietary fibre contents but lower protein, fat and carbohydrate contents than the
      BCtr. Bread incorporated with BPF resulted in a lower volume, darker crumb and
      lighter crust colour than the BCtr. The addition of CMC improved the bread
      volume. All breads containing BPF had greater total phenolics, and antioxidant
      properties than the control bread. Sensory evaluation indicated that the
      B10BPFCMC bread had the highest acceptability.

PMID- 23561143
TI  - Variation in nutritionally relevant components in retail Jersey and Guernsey
      whole milk.
AB  - This study investigates the quality of retail milk labelled as Jersey & Guernsey
      (JG) when compared with milk without breed specifications (NS) and repeatability
      of differences over seasons and years. 16 different brands of milk (4 Jersey &
      Guernsey, 12 non specified breed) were sampled over 2 years on 4 occasions. JG
      milk was associated with both favourable traits for human health, such as the
      higher total protein, total casein, alpha-casein, beta-casein, kappa-casein and
      alpha-tocopherol contents, and unfavourable traits, such as the higher
      concentrations of saturated fat, C12:0, C14:0 and lower concentrations of
      monounsaturated fatty acids. In summer, JG milk had a higher omega-3:omega-6
      ratio than had NS milk. Also, the relative increase in omega-3 fatty acids and
      alpha-tocopherol, from winter to summer, was greater in JG milk. The latter
      characteristic could be of use in breeding schemes and farming systems producing
      niche dairy products. Seasonality had a more marked impact on the fatty acid
      composition of JG milk than had NS milk, while the opposite was found for protein
      composition. Potential implication for the findings in human health, producers,
      industry and consumers are considered.

PMID- 23561144
TI  - Proportions of A1, A2, B and C beta-casein protein variants in retail milk in the
      UK.
AB  - The A1 variant protein of the beta-casein family has been implicated in various
      disease states although much evidence is weak or contradictory. The primary
      objective was to measure, for the first time, the proportions of the key beta
      casein variant proteins in UK retail milk over the course of one year. In total,
      55 samples of semi-skimmed milk were purchased from five supermarkets over the
      course of a year and the proportions of the A1, A2, B and C casein variant
      proteins were measured, using high resolution HPLC-MS. The results showed that
      beta-casein in UK retail milk comprises approximately 0.58, 0.31, 0.07 and 0.03
      A2, A1, B and C protein variants, respectively. The proportion of A2 is higher
      than some early studies would predict although the reasons for this and any
      implications for health are unclear.

PMID- 23561145
TI  - RP-HPLC and chemometrics for wheat flour protein characterisation in an
      industrial bread-making process monitoring context.
AB  - In the baking industry, a difficult task is to keep the quality perceived by the
      consumer as constant as possible, given the inner variability of flour, e.g. due
      to different wheat mixtures, harvesting time, etc. Here, we evaluated the
      influence of flour batches properties on bread quality, considering an industrial
      bread making process. In particular, flour composition in terms of protein
      fractions (gliadins, glutenins) has been determined by means of RP-HPLC, to
      assess the inter- and intra-batch variability of flour mixtures deliveries at a
      baking plant. Multivariate data analysis allowed evaluation of correlation
      between flour protein composition and technological properties. A great
      variability within different deliveries of a same flour batch emerged, as well as
      a considerable seasonal variability. Correlation models among protein sub
      fractions, technological properties and bread quality are difficult to establish;
      however, the role of the protein profile on flour behaviour in bread making could
      be highlighted.

PMID- 23561146
TI  - Preparative isolation and purification of seven main antioxidants from Eucommia
      ulmoides Oliv. (Du-zhong) leaves using HSCCC guided by DPPH-HPLC experiment.
AB  - Seven antioxidants were purified from Eucommia ulmoides Oliv. leaves using HSCCC
      guided by DPPH-HPLC experiment. HSCCC was successfully used to separate target
      antioxidants by three runs with different solvent systems after D101 column
      chromatography fractionation. Ethyl acetate-n-butanol-water (1:2:3, v/v/v) was
      selected as the optimum solvent system to purify geniposidic acid. Ethyl acetate
      ethanol-water (4:1:5, v/v/v) was used to isolate caffeic acid, chlorogenic acid
      and ferulic acid. While three flavonoids, quercetin-3-O-sambubioside, rutin and
      isoquercitrin were purified by petroleum ether-ethyl acetate-methanol-water
      (1:5:1:5, v/v/v/v). The structures were identified by MS and NMR. Antioxidant
      activities were assessed, and compounds 2-7 showed strong antioxidant activities.
      This is the first report about separation of antioxidants from E. ulmoides leaves
      by HSCCC. The results indicated that the combinative methods using DPPH-HPLC and
      HSCCC could be widely applied for screening and isolation of antioxidants from
      complex extracts.

PMID- 23561147
TI  - The effect of interesterification on the bioavailability of fatty acids in
      structured lipids.
AB  - Fatty acid (FA) profile is a critical factor in the nutritional properties of
      fats, but, stereochemistry may also play a fundamental role in the rate and
      extent to which FAs are absorbed and become available. To better understand this
      phenomenon, we evaluated the bioavailability of FAs in linseed-oil and palm
      stearin blends compared to their interesterified mix, using a sn-1,3
      stereospecific lipase, to determine if there was any difference in terms of FA
      availability when using this technology. Test meals were fed through an
      intragastric feeding tube on Sprague-Dawley male rats after 18 h fasting.
      Postprandial blood samples were collected after meal or physiological serum
      (control) administration and the FA profile of plasma lipids was determined.
      Results showed that modification of the melting profile through
      interesterification, without altering the bioavailability determined by sn-2
      stereochemistry, could delay lipid absorption at the beginning, but had no effect
      on total lipid absorption.

PMID- 23561148
TI  - Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics,
      vitamin C and antioxidant capacity of two powder products from camu-camu fruit
      (Myrciaria dubia).
AB  - The aims of this study were the evaluation of polyphenols and vitamin C content,
      and antioxidant capacity of dehydrated pulp powder and the dried flour obtained
      from the skin and seeds residue remaining after pulp preparation from camu-camu
      (Myrciaria dudia). Fifty-three different phenolics were characterised by HPLC-DAD
      ESI-MS-MS and UPLC-HR-QTOF-MS-MS. The phenolic content of camu-camu flour was
      higher than that of the pulp powder (4007.95 mg/100 g vs. 48.54 mg/100 g). In
      both products the flavonol myricetin and conjugates, ellagic acid and conjugates
      and ellagitannins were detected. Cyanidin 3-glucoside, and quercetin and its
      glycosides were only found in the pulp powder, while proanthocyanidins were only
      present in the flour (3.5 g/100 g, mean degree of polymerisation 3). The vitamin
      C content was lower in pulp powder (3.5%) than in the flour (9.1%). The radical
      scavenging capacity of both powders was determined by the DPPH, ABTS and ORAC
      assays, and was higher for camu-camu flour as could be expected for its higher
      phenolics and vitamin C content. Comparative analyses with fresh camu-camu
      berries indicate that some transformations occur during processing. Analysis of
      fresh berries showed that ellagic acid derivatives and ellagitannins were mainly
      present in the seeds, while proanthocyanidins were present both in the seeds and
      skin.

PMID- 23561149
TI  - Plasma and hepatic cholesterol-lowering effects of tomato pomace, tomato seed oil
      and defatted tomato seed in hamsters fed with high-fat diets.
AB  - The cholesterol-lowering effects of tomato pomace (TP), tomato seed oil (TSO) and
      defatted tomato seed (DTS) were determined in male Golden Syrian hamsters.
      Hamsters fed high-fat diets containing 10% TSO or 18% DTS were compared to a diet
      containing 10% corn oil and 10% microcrystalline cellulose (control 1), 42% TP
      were compared to 25% microcrystalline cellulose (control 2). TP, TSO and DTS
      reduced hepatic total cholesterol (TC) content. DTS also lowered plasma TC and
      low-density lipoprotein cholesterol (LDL-C) concentrations. Fecal excretion of
      lipid, bile acid and cholesterol increased in the DTS group compared to control
      1. DTS-fed hamsters had higher levels of hepatic CYP7A1, CYP51, ABCB11, and ABCG5
      gene expression than control, suggesting both hepatic bile acid and cholesterol
      synthesis increased due to increased fecal excretion of bile acid and
      cholesterol. The results suggest that protein, dietary fibre or phenolic
      compounds in DTS may be responsible for plasma cholesterol decrease.

PMID- 23561150
TI  - Tenderization effect of soy sauce on beef M. biceps femoris.
AB  - This study was conducted to evaluate the tenderization effect of soy sauce on
      beef M. biceps femoris (BF). Five marinades were prepared with 4% (w/v) sodium
      chloride and 25% (w/v) soy sauce solutions (4% salt concentration) and mixed with
      the ratios of 100:0 (S0, pH 6.52), 75:25 (S25, 5.40) 50:50 (S50, 5.24), 25:75
      (S75, 5.05), and 0:100 (S100, 4.85), respectively. The BF samples which were
      obtained from Hanwoo cows at 48 h postmortem (n=24) were marinated with five
      marinades for 72 h at 4 degrees C (1:4 w/w), and the effects of soy sauce on
      tenderness were evaluated. Soy sauce marination resulted in a decrease in the pH
      value of the BF sample. However, there were no significant differences in the
      water holding capacity (P<0.05). The S100 treatment showed the significant
      (P<0.05) increase in collagen solubility and myofibrillar fragmentation index,
      contributing to decreased shear force compared to S0 (control). Reduction in
      intensity of few myofibrillar protein bands were observed for S100 treatment
      compared to control using SDS-PAGE. Scanning electron microscopy revealed
      breakdown of connective tissue surrounding muscle fibers of the S100 treatment.
      The tenderization effect of soy sauce may attribute various mechanisms such as
      increased collagen solubility or proteolysis which depend on soy sauce level in
      marinade.

PMID- 23561151
TI  - Anthocyanins in the ripe fruits of Rubus coreanus Miquel and their protective
      effect on neuronal PC-12 cells.
AB  - Phenolics of the fresh ripe fruits of Rubus coreanus Miquel were extracted and
      separated into anthocyanin and the non-anthocyanin fractions, which were used for
      the evaluation for antioxidant capacity and neuroprotective effects. The
      anthocyanin fraction accounted for approximately 47-55% of the total antioxidant
      capacity of the whole extract and had significantly higher free radical
      scavenging capacity than the non-anthocyanin fraction. Furthermore, the
      anthocyanins alleviated intracellular oxidative stress, as assayed by in vitro
      fluorescent measurements. The anthocyanins showed neuroprotective effects on PC
      12 cells in vitro against oxidative stress in a dose-dependent manner. Triple
      quadrupole LC/MS and Q-TOF LC/MS analyses revealed four major anthocyanins;
      cyanidin 3-O-sambubioside, cyanidin 3-O-glucoside, cyanidin 3-O
      xylosylrutinoside, and cyanidin 3-O-rutinoside in increasing order of amounts.
      These results demonstrated that anthocyanins are the major components and
      contributors to the antioxidant capacity of ripe R. coreanus Miquel fruits.
      Further studies are warranted to determine whether consumption of the fruits
      reduces oxidative stress in the brain and promotes health.

PMID- 23561152
TI  - Probing the binding between norbixin and dairy proteins by spectroscopy methods.
AB  - Annatto (norbixin) has been used to color cheeses for centuries, but there is
      very little knowledge about interactions between the pigment and dairy proteins.
      In this study, binding of norbixin with whey protein isolate (WPI), sodium
      caseinate (NaCN), and 6 individual dairy proteins was investigated by using
      fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR),
      circular dichroism (CD) and differential scanning calorimetry (DSC). Norbixin was
      observed to effectively quench the fluorescence of WPI and NaCN by forming
      complexes. The binding affinity between NaCN and norbixin was higher than that of
      WPI-norbixin. For individual proteins, bovine serum albumin had higher binding
      affinity with norbixin than beta-lactoglobulin and alpha-lactalbumin, while kappa
      casein bound with norbixin better than alpha- and beta-caseins. Binding changed
      the conformation of WPI and NaCN, but the extent and trend varied for individual
      proteins.

PMID- 23561153
TI  - Extraction and structural characterisation of rhamnogalacturonan I-type pectic
      polysaccharides from potato cell wall.
AB  - Cell wall material from potato pulp by-product was used for the extraction of
      galactan-rich rhamnogalacturonan I (RG-I) type pectic polysaccharides using
      alkaline (NaOH and KOH) and enzymatic (endopolygalacturonase from Aspergillus
      niger) methods. The extraction yield increased as the concentration of alkaline
      solution was increased from 0.5 M (22-24%) to 2 M (53-56%). The yield of 38%
      obtained upon the enzymatic treatment was similar to those observed with 1M
      alkaline solutions. The results reveal the high debranching of arabinan side
      chains of RG I as compared to the galactan ones under harsh alkaline conditions.
      The molecular weight distribution shows that the enzymatic extraction led to the
      highest proportion of high-molecular weight polysaccharides (>500 kDa; 62.2%).
      According to monosaccharide pattern, the weak acidic fractions of high alkaline
      (1-2 M)-based polysaccharide extracts was the most enriched with galactan-rich RG
      I. Using milder conditions (enzyme and weak alkaline), two RG I populations with
      low and high linked homogalacturonan fragments were recovered in the weak and
      strong acidic fractions, respectively. The structure of galactan-rich RG I was
      confirmed by H(1) NMR spectroscopy analysis.

PMID- 23561154
TI  - Effects of NaCl and pH on the structural conformations of kidney bean vicilin.
AB  - Structural changes as a result of variations in pH value and salt concentration
      were determined for purified vicilin, the major globular protein in kidney beans
      using intrinsic fluorescence and circular dichroism (CD). The vicilin consisted
      of two polypeptide chains of about 43 and 45 kDa in size when analysed under
      reducing SDS-PAGE. Amino acid analysis showed that the vicilin had high contents
      of acidic amino acids and a low lysine/arginine ratio. Intrinsic fluorescence
      measurements were performed to measure exposure of tyrosine and tryptophan as a
      means of estimating protein conformational changes. Generally, the vicilin showed
      an unfolded structure at pH 3.0, 5.0, 7.0, and 9.0 as evident by the extensive
      red shift (>350 nm) of the wavelength of maximum tryptophan fluorescence
      intensity. At pH 3.0 and 5.0, the fluorescence intensity (FI) was greater than
      values obtained at pH 7.0 and 9.0, which suggests that the microenvironment of
      tryptophan was less hydrophilic at acidic pH. Addition of NaCl also led to
      increased FI, an indication of structural changes of tryptophan in response to
      the hydrophilic environment. These changes in FI were due mostly to tryptophan
      emission because tyrosine emission (at 303 nm) was suppressed. The far-UV CD
      spectra showed that vicilin had minimal measurable secondary structures at pH 3.0
      and 5.0 when compared to pH 7.0 and 9.0. Addition of NaCl led to an increase in
      the tertiary structure conformation of vicilin as determined from the near-UV CD
      spectra.

PMID- 23561155
TI  - Biosynthesis of highly enriched 13C-lycopene for human metabolic studies using
      repeated batch tomato cell culturing with 13C-glucose.
AB  - While putative disease-preventing lycopene metabolites are found in both tomato
      (Solanum lycopersicum) products and in their consumers, mammalian lycopene
      metabolism is poorly understood. Advances in tomato cell culturing techniques
      offer an economical tool for generation of highly-enriched (13)C-lycopene for
      human bioavailability and metabolism studies. To enhance the (13)C-enrichment and
      yields of labelled lycopene from the hp-1 tomato cell line, cultures were first
      grown in (13)C-glucose media for three serial batches and produced increasing
      proportions of uniformly labelled lycopene (14.3+/-1.2%, 39.6+/-0.5%, and 48.9+/
      1.5%) with consistent yields (from 5.8 to 9 mg/L). An optimised 9-day-long (13)C
      loading and 18-day-long labelling strategy developed based on glucose utilisation
      and lycopene yields, yielded (13)C-lycopene with 93% (13)C isotopic purity, and
      55% of isotopomers were uniformly labelled. Furthermore, an optimised acetone and
      hexane extraction led to a fourfold increase in lycopene recovery from cultures
      compared to a standard extraction.

PMID- 23561156
TI  - Effect of recovery methods on the oxidative and physical stability of oil body
      emulsions.
AB  - Three natural oil body emulsions of a similar fat content (~5%), but differing in
      their protein composition were obtained from an aqueous maize germ extract. The
      first was prepared by concentrating the aqueous oil body extract with
      ultrafiltration to a fat content of ~5%. The other two were prepared by initially
      recovering the oil bodies from the extract by centrifugation, either in the
      presence of sucrose or by applying isoelectric precipitation at pH 5.0 and then
      diluting the resulting oil body creams with deionized water. The oxidative and
      physical stability of the three emulsions, either as they were or after
      submission to thermal treatment (100 degrees C for 15 min), were studied
      following storage at 45 degrees C. The emulsions differed both in their oxidative
      and physical stability, depending on the recovery method that in turn influenced
      their continuous phase and/or interfacial membrane protein and/or polar
      antioxidant composition. Ultrafiltration resulted in the most stable emulsion.
      Mixtures of the natural oil body emulsions with green tea extracts, aiming to
      serve as a base for functional beverages, were then prepared and studied for
      their creaming behaviour. The green tea polyphenols seem to interact with the oil
      bodies leading to intensive dispersion destabilisation which, however, was halted
      following carrageenan addition at a relatively very low level.

PMID- 23561157
TI  - Characterization of Hachi (Camelus dromedarius) fat extracted from the hump.
AB  - In this work, the characteristics of fat from the hump of young camels (Hachi)
      were evaluated. The physicochemical properties of the fat were as follows:
      melting point, 45 degrees C; saponification value, 202.3 mg KOH/g oil; refractive
      index (60 degrees C), 1.468; unsaponifiable matter, 1.37%; free fatty acids (as
      the percentage of oleic acid), 0.96%; and peroxide value, 3.37 mequiv. O2/kg oil.
      High-resolution (1)H nuclear magnetic resonance ((1)H NMR) was used for the
      direct determination of the iodine value of Hachi fat (62.74 g/100 g oil). The
      Hachi fat was composed primarily of oleic acid (33.35%), followed by palmitic
      acid (26.16%), stearic acid (10.07%), palmitelaidic acid (9.56%) and myristic
      acid (8.83%). The thermal properties were assessed by thermogravimetry (TG) and
      derivative thermogravimetry (DTG). The results of the present analytical study
      showed that Hachi fat could be used in food products and as an important source
      of biological materials.

PMID- 23561159
TI  - Distribution of carotenoids in endosperm, germ, and aleurone fractions of cereal
      grain kernels.
AB  - To compare the distribution of carotenoids across the grain, non-corn and corn
      cereals were hand dissected into endosperm, germ and aleurone fractions. Total
      carotenoid content (TCC) and carotenoid composition were analysed using
      spectrophotometry and HPLC. Cereal carotenoid composition was similar; however,
      concentrations varied significantly (p<0.05). Endosperm fractions had TCC ranging
      from 0.88 to 2.27 and 14.17 to 31.35 mg/kg in non-corn cereals and corn,
      respectively. TCC, lutein and zeaxanthin in germ fractions were higher in non
      corn cereals than in corn. Lutein and zeaxanthin contents were lower in non-corn
      cereal endosperms. The aleurone layer had zeaxanthin levels 2- to 5-fold higher
      than lutein among the cereals. Positive significant correlations (p<0.05) were
      found between TCC, carotenoids analysed by HPLC and DPPH results. This study is
      the first to report on carotenoid composition of the aleurone layer. Our findings
      suggest that the aleurone of wheat, oat, corn and germ of barley have
      significantly enhanced carotenoid levels.

PMID- 23561158
TI  - A method for determining regioisomer abundances of polyunsaturated
      triacylglycerols in omega-3 enriched fish oils using reversed-phase liquid
      chromatography and triple-stage mass spectrometry.
AB  - Reversed-phase high performance liquid chromatography (RP-HPLC), followed by post
      column addition of lithium salts and electrospray ionisation triple-stage mass
      spectrometry (ESI-MS(3)) of lithiated TAG adducts, is shown to provide a useful
      method for the positional analysis of triacylglycerols (TAGs) in fish oils
      containing eicosapentaenoic (EPA, 20:5) and docosahexaenoic acids (DHA, 22:6).
      One prominent fragmentation pathway in the ESI-MS(3) of these adduct ions
      involves the loss of a fatty acid from the sn-1/3 position in the first step
      followed by the loss of an alpha,beta-unsaturated fatty acid from the sn-2
      position in the second. Regioisomeric TAGs of the type ABA and AAB produced
      abundant product ions - [ABA+Li-RACOOH-R'BCHCHCOOH](+) and [AAB+Li-RACOOH
      R'ACHCHCOOH](+) - the relative intensities of which were dependent on the
      position of acyl substituents. Standard solutions of TAGs containing different
      ratios of the regioisomeric pairs MME/MEM, PPE/PEP, PPD/PDP, EEP/EPE and DDP/DPD
      (M=14:0, P=16:0, E=20:5, D=22:6) were analysed by ESI-MS(3) with a quadrupole
      linear ion trap instrument. Methodology developed on the standards was applied to
      quantifying the relative isomeric abundances of EPA and DHA in several fish oil
      samples. DHA was preferentially located at the sn-2 position in both DHA
      containing TAGs studied, while EPA was either observed at near equal levels in
      all positions, or predominantly at the sn-1 and -3 positions in some cases. The
      analysis protocol allows for quantification of the designated regioisomers in one
      simple, rapid chromatographic procedure using a single column and has the
      advantage of specificity over other methods for the positional analysis of TAGs,
      since it eliminates interferences associated with co-eluting TAGs of the same
      molecular weight that yield isobaric diacylglycerol-like product ions.

PMID- 23561160
TI  - Effect of temperature on the release of intentionally and non-intentionally added
      substances from polyethylene terephthalate (PET) bottles into water: chemical
      analysis and potential toxicity.
AB  - The purpose of this study was to investigate the impact of temperature on the
      release of PET-bottle constituents into water and to assess the potential health
      hazard using in vitro bioassays with bacteria and human cell lines. Aldehydes,
      trace metals and other compounds found in plastic packaging were analysed in PET
      bottled water stored at different temperatures: 40, 50, and 60 degrees C. In this
      study, temperature and the presence of CO2 increased the release of formaldehyde,
      acetaldehyde and antimony (Sb). In parallel, genotoxicity assays (Ames and
      micronucleus assays) and transcriptional-reporter gene assays for estrogenic and
      anti-androgenic activity were performed on bottled water extracts at relevant
      consumer exposure levels. As expected, and in accordance with the chemical
      formulations specified for PET bottles, neither phthalates nor UV stabilisers
      were present in the water extracts. However, 2,4-di-tert-butylphenol, a
      degradation compound of phenolic antioxidants, was detected. In addition, an
      intermediary monomer, bis(2-hydroxyethyl)terephthalate, was found but only in PET
      bottled waters. None of the compounds are on the positive list of EU Regulation
      No. 10/2011. However, the PET-bottled water extracts did not induce any
      cytotoxic, genotoxic or endocrine-disruption activity in the bioassays after
      exposure.

PMID- 23561161
TI  - Effect of calcium on the kinetics of free fatty acid release during in vitro
      lipid digestion in model emulsions.
AB  - The effects of different calcium salts on in vitro lipid digestion were examined
      by determining the free fatty acids released from various oil-in-water emulsions.
      The kinetics of the total and individual free fatty acids released by lipolysis
      were monitored by the pH-stat method and gas chromatography, respectively. The
      rate and the extent of free fatty acid release increased with an increase in the
      added calcium concentration, but the increase was dependent on the emulsifying
      agent. The effect of calcium was diminished when the emulsion contained
      phosphate. Soluble calcium salts, such as calcium gluconate, calcium acetate and
      CaCl2, had greater effects on the rate and extent of free fatty acid release than
      did insoluble salts, such as CaO and CaSO4, suggesting that the ionic state of
      calcium plays a critical role in lipid digestion in emulsions. The addition of
      calcium did not alter the profiles of the individual free fatty acids released.
      This study provides useful information for food formulation with respect to lipid
      digestion.

PMID- 23561162
TI  - Monitoring green leaf tea quality parameters of different TV clones grown in
      northeast India using satellite data.
AB  - This study tries to quantify the effects of green leaf tea parameters that
      influence tea quality in Northeast India. The study is to identify the different
      parameters that have a significant influence on tea quality through the use of
      remote sensing. It investigates the methods for estimating tea quality based on
      remotely sensed Normalized Difference Vegetation Index (NDVI) data. Attention
      focused on high yielding TV clones (TV1, TV18, TV22, TV23, TV25 and TV26). NDVI
      was obtained from ASTER images. Statistical analysis shows that NDVI has a strong
      significant effect on the caffeine content followed by epicatechin (EC),
      epigallocatechin (EGC) and to some extent in other chemical parameters.
      Relationships therefore exist between quality parameters and remote sensing in
      particular for the TV clones. This leads to the conclusion that NDVI has a large
      potential to be used for monitoring tea quality of individual cultivars in the
      future.

PMID- 23561163
TI  - Congeners in sugar cane spirits aged in casks of different woods.
AB  - The profile of volatile compounds and aging markers in sugar cane spirits aged
      for 36 months in casks made of 10 types of wood were studied. The ethanol
      content, volatile acidity, aldehydes, esters, higher alcohols, and methanol were
      determined. In addition, gallic, vanilic and syringic acids, siringaldehyde,
      coniferaldehyde, sinapaldehyde, vanillin, 5-hydroxymethylfurfural and furfural
      were identified and quantified. The profile of volatile compounds characterised
      aging in each type of wood. The beverage aged in oak cask achieved the highest
      contents of maturation-related congeners. The Brazilian woods, similar to oak,
      were jequitiba rosa and cerejeira, which presented the highest contents of some
      maturation-related compounds, such as vanillin, vanilic acid, syringaldehyde and
      sinapaldehyde. Although oak wood conferred more chemical complexity to the
      beverage, Brazilian woods, singly or complementarily, present potential for
      spirit characterisation and for improving the quality of sugar cane spirits.

PMID- 23561164
TI  - Enzymatic preparation and structural determination of oligosaccharides derived
      from sea cucumber (Acaudina molpadioides) fucoidan.
AB  - Sea cucumber fucoidan is a major bioactive component of sea cucumber. Sea
      cucumber is widely consumed in East Asian countries as healthy food. Employing
      the degrading enzyme from the marine bacterium strain Flavobacteriaceae CZ1127,
      sea cucumber (Acaudina molpadioides) fucoidan oligosaccharides were prepared by
      enzymatic hydrolysis. The oligosaccharide profile of the hydrolysate was
      determined by liquid chromatography coupled with mass spectrometry (LC-MS). With
      the assistance of LC-MS, four major oligosaccharides in the hydrolysate were
      purified. By using tandem mass spectrometry and nuclear magnetic resonance,
      delicate structures of the oligosaccharides were verified as alpha-l-Fucp-1->3
      alpha-l-Fucp(2,4OSO3(2-))-1->3-alpha-l-Fucp, alpha-l-Fucp-1->3-alpha-l
      Fucp(2,4OSO3(2-))-1->3-alpha-l-Fucp-1->3-alpha-l-Fucp, alpha-l-Fucp-1->3-alpha-l
      Fucp(2,4OSO3(2-))-1->3-alpha-l-Fucp-1->3-alpha-l-Fucp-1->3-alpha-l-Fucp-1->3
      alpha-l-Fucp(2,4OSO3(2-))-1->3-alpha-l-Fucp and alpha-l-Fucp-1->3-alpha-l
      Fucp(2,4OSO3(2-))-1->3-alpha-l-Fucp-1->3-alpha-l-Fucp-1->3-alpha-l-Fucp-1->3
      alpha-l-Fucp(2,4OSO3(2-))-1->3-alpha-l-Fucp-1->3-alpha-l-Fucp.

PMID- 23561165
TI  - Chemical, rheological and surface morphologic characterisation of spent hen
      proteins extracted by pH-shift processing with or without the presence of
      cryoprotectants.
AB  - The chemical and rheological properties of spent hen proteins recovered by acid
      and alkaline extraction have been studied with/without cryoprotectants (CP) after
      3 weeks of frozen storage. Four pH values (2.0, 2.5, 11.5, and 12.0) were used
      for extraction. CP addition prevented freeze-induced denaturation and oxidation
      in all extracted proteins, as revealed by significant increases in reactive
      sulphydryl groups (p<0.0001), and a decrease in the formation of carbonyl groups
      (p<0.0001). The alkaline extracted proteins with CP formed more viscoelastic gels
      compared to the others, while samples without CP failed to form a gel network.
      FTIR of the protein isolates with CP showed a protective effect on the secondary
      structure of the isolated proteins. Scanning electron micrographs showed a
      protective shield of CP around the isolated proteins.

PMID- 23561166
TI  - Effects of fisetin supplementation on hepatic lipogenesis and glucose metabolism
      in Sprague-Dawley rats fed on a high fat diet.
AB  - The modulatory effects of daily fisetin supplementation for 8 weeks on genes
      involved in hepatic lipogenesis and gluconeogenesis and hyperglycemia in rats fed
      a high fat (HF) diet were evaluated. Elevated levels of triglyceride (TG), along
      with hepatic TG content and glucose concentrations in a high fat diet group were
      found to be reduced by fisetin supplementation. The high fat diet significantly
      increased hepatic mRNA expressions of PPARgamma, SREBP1C and SCD-1 genes in
      comparison to the control diet, which was subsequently reversed by
      supplementation with fisetin. In addition, fisetin supplementation significantly
      reduced hepatic mRNA abundance of FAS, ATPCL and G6Pase compared to the control
      group. Finally, epididymal mRNA abundance of GLUT4 was significantly increased by
      fisetin supplementation, compared to levels in the control and HF groups.
      Enhancement of GLUT4 expression by fisetin was further confirmed in
      differentiated 3T3-L1 adipocytes. Fisetin supplementation decreases
      cardiovascular risks by ameliorating hepatic steatosis and lowering circulating
      glucose concentrations.

PMID- 23561167
TI  - Aluminium and other elements in selected herbal tea plant species and their
      infusions.
AB  - The determination of Al, B, Cu, Fe, Mn, Ni, P, Zn and Ca, K, Mg by inductively
      coupled plasma optical emission spectrometry (ICP-OES) and flame atomic
      absorption spectroscopy (FAAS), respectively, in digests and infusions of
      Hibiscus sabdariffa (petals), Rosa canina (receptacles), Ginkgo biloba (leaves),
      Cymbopogon citratus (leaves), Aloe vera (leaves) and Panax ginseng (roots) was
      carried out in this study. Particular attention has been given to Al and heavy
      metals for the identification of possible raw material contaminants, their
      transformation into the infusion and for predicting their eventual role in the
      human diet during daily consumption. Additionally, Ion Chromatography (IC)
      speciation of Al in the leachates was carried out. In dry herbs, hibiscus and
      ginkgo appeared to contain the greatest contents of Al, Fe, K, Mn, Ni, Zn and B,
      Mg, P, respectively. A. vera contained the highest amount of Ca and highest
      values of Cu and P were observed in ginseng. In infusions, the topmost
      concentrations of Al, B, Cu, Fe, P, K, Mn, Ni, Zn were detected in those prepared
      from hibiscus petals, Ca from aloe leaves and Mg from leaves of ginkgo. According
      to a possible daily consumption exceeding 1 L, hibiscus decoction was identified
      as potentially dietetically significant in the content of certain elements. It
      seems to be possibly one of the top contributors of B from food (up to 5.5+/-0.2
      mg/L). The Mg contained in the infusion (up to 106+/-5 mg/L) may be a contributor
      in the attenuation of blood pressure. A high amount of accessible Mn (up to
      17.4+/-1.1 mg/L) can probably have an adverse effect in humans. The total Al
      allowance (up to 1.2+/-0.1 mg/L) suggests that no more than 1 L of the hibiscus
      infusion should be consumed per day by sensitive individuals including pregnant
      women and should be completely excluded from the diet of children under 6 months
      of age and children with chronic renal failure.

PMID- 23561168
TI  - Cultivar variations in antioxidant and antihyperlipidemic properties of pomelo
      pulp (Citrus grandis [L.] Osbeck) in Thailand.
AB  - Pomelo (Citrus grandis L. Osbeck) is a native fruit of great economic importance
      in Southeast Asia. To provide experimental evidence for the antioxidant and
      antihyperlipidemic properties of pomelo, 6 cultivars, including Kao-Yai (KY),
      Thong-dee (TD), Kao-Tangkwa (KT), Kao-Numpueng (KN), Ta-Koi (TK), and Tubtim Siam
      (TS) were evaluated. KY had the highest phenolic content, and the strongest 1,1
      diphenyl-2-pireyhydrazyl radical scavenging capacity and hydroxyl radical
      scavenging activity. From the high-performance liquid chromatography analysis,
      naringin and naringenin were the major flavonoids in the KT and TK cultivars. Six
      pomelo cultivars had antihyperlipidemic activities including the inhibition of
      pancreatic lipase and cholesterol esterase, as well as cholesterol micelle
      formation and bile acid binding. Hierarchical clustering analysis showed that the
      6 cultivars were separated into 2 classifications. In addition, the total
      phenolics of the pomelo cultivars were significantly correlated with ferric
      reducing antioxidant power and Trolox equivalent antioxidant capacity. The
      results suggest that pomelo provides significant health benefits and may be used
      for developing functional foods.

PMID- 23561169
TI  - Carotenoids and tocopherols in yellow and red raspberries.
AB  - The composition of carotenoids, chlorophyll derivatives and tocopherols in
      raspberries of different varieties, including yellow and red varieties, over
      different ripening stages has been studied. The profile of pigments in ripening
      raspberries changes drastically, with a dramatic decrease of beta-carotene and
      chlorophyll derivatives, the xanthophyll lutein has also decreased but not to the
      same extent. In contrast esterified lutein increased and is present in ripe
      raspberries esterified with saturated fatty acids with C8-C16 chains. Ripe
      raspberries contain considerable amounts of free lutein, esterified lutein, and
      tocopherols (up to 20, 49 and 366 mg/kg dry weight, respectively). The different
      samples analysed show different contents of carotenoids and tocopherols. Whether
      the differences arise from the variety or other factors such as the environmental
      conditions needs to be ascertained but isoprenoids should not be neglected when
      considering raspberry antioxidant and nutraceutical composition.

PMID- 23561170
TI  - Enrichment of polyphenol contents and antioxidant activities of Irish brown
      macroalgae using food-friendly techniques based on polarity and molecular size.
AB  - An efficient, food-friendly process for the enrichment of macroalgal
      phlorotannins from solid-liquid extracts (SLE) of three brown macroalgae, namely
      Fucus spiralis Linnaeus, Pelvetia canaliculata (Linnaeus) Decaisne & Thuret and
      Ascophyllum nodosum (Linnaeus) Le Jolis, has been demonstrated. The initial
      utilisation of molecular weight cut-off (MWCO) dialysis generated fractions of
      low molecular weight (LMW) (<3.5 kDa) and of high molecular weight (HMW) (3.5-100
      kDa and >100 kDa) from cold water, hot water and aqueous ethanolic SLE extracts.
      An enhancement of the total phenolic content (TPC), radical scavenging abilities
      (RSA) and ferric reducing antioxidant power (FRAP) in the HMW fractions of 3.5
      100 kDa and/or >100 kDa from the cold water and aqueous ethanolic extracts was
      observed. The initial weak TPC, RSA and FRAP observed in the LMW fractions
      relative to the HMW fractions were substantially enhanced following a reverse
      phase flash chromatography fractionation method. Quadrupole time-of-flight mass
      spectrometry (Q-Tof-MS) suggests that phlorotannins of varying degrees of
      phloroglucinol polymerisation are present in LMW fractions of the three brown
      macroalgal species. The development of a food-friendly process for the extraction
      and enrichment of phlorotannins from Irish macroalgae is vital to facilitate the
      use of this valuable resource in future developments of macroalgal-based
      functional foods.

PMID- 23561171
TI  - Rapid chemical profiling of saponins in the flower buds of Panax notoginseng by
      integrating MCI gel column chromatography and liquid chromatography/mass
      spectrometry analysis.
AB  - The flower buds of Panax notoginseng (Notoginseng flower, FBP) are used as the
      traditional Chinese medicine San-Qi-Hua. In this study, we conducted column
      chromatography fractionation and liquid chromatography/mass spectrometry (LC/MS)
      analysis to comprehensively profile bioactive notoginseng saponins (ginsenosides)
      in FBP. MCI gel column chromatography allowed separation and enrichment of minor
      saponins. Electrospray ionization tandem mass spectrometry of [M-H](-) and
      [M+Na](+) precursor ions of the saponins provided reliable structural information
      for the sapogenin, and sequence of sugar chains. Confirmed by high-accuracy Q-TOF
      analysis, 170 notoginseng saponins were characterized from FBP, and 91 of them
      were reported from Panax species for the first time. The new ginsenosides contain
      acyl groups on alpha-chain, malonyl group at 20-OH, or di-malonyl groups. This
      study also indicated that the flower buds of P. notoginseng contained more
      protopanaxadiol-type but less protopanaxatriol-type ginsenosides than the roots.

PMID- 23561172
TI  - Influence of cold pre-fermentation treatments on the major volatile compounds of
      three wine varieties.
AB  - The volatile compounds of wines made from three grape varieties (Monastrell,
      Cabernet Sauvignon and Syrah) using three pre-fermentation techniques (grape
      freezing, dry-ice and cold maceration) and a control treatment were measured. The
      different winemaking practices, which are intended to increase the aromatic
      properties of wines, produced results that depended on the variety concerned. For
      example, freezing the Cabernet Sauvignon and Syrah grapes produced different
      results compared with the respective controls, whereas few changes were found on
      freezing the Monastrell wine. Differences were significant in the case of some
      volatile compounds. Linear discriminant analysis allowed some grouping of the
      varieties at sampling but not of the pre-fermentation techniques used.

PMID- 23561173
TI  - Chemical properties of omega-3 fortified gels made of protein isolate recovered
      with isoelectric solubilisation/precipitation from whole fish.
AB  - Protein isolate was recovered from whole gutted fish using isoelectric
      solubilisation/precipitation (ISP). The objective was to determine chemical
      properties of heat-set gels made of the ISP protein isolate fortified with omega
      3 polyunsaturated fatty acids (PUFAs)-rich oils (flaxseed, fish, algae, krill,
      and blend). The extent of the PUFAs increase, omega-6/omega-3 FAs and
      unsaturated/saturated FAs ratios, and the indices of thrombogenicity and
      atherogenicity depended on specific omega-3 PUFAs-rich oil used to fortify
      protein isolate gels. Lipid oxidation in omega-3 PUFAs fortified gels was
      minimal, although greater (P<0.05) than control gels (without omega-3 PUFAs
      fortification). However, all gels were in the slightly rancid, but acceptable
      range. The commonly used thiobarbituric-acid-reactive-substances (TBARS) assay to
      determine lipid oxidation in seafood may be inaccurate for samples containing
      krill oil due to its red pigment, astaxanthin. Protein degradation (total
      volatile-basic-nitrogen) was greater (P<0.05) in omega-3 PUFAs fortified gels
      than control gels. However, all gels were considerably below the acceptability
      threshold for protein degradation. The shear stress of omega-3 PUFAs fortified
      gels was generally greater than the control gels and the shear strain was
      generally unchanged. This study demonstrates that omega-3 PUFAs fortification of
      protein isolates recovered with ISP from fish processing by-products or whole
      fish has potential application in the development of functional foods.

PMID- 23561174
TI  - Characterisation of chlorophyll oxidation mediated by peroxidative activity in
      olives (Olea europaea L.) cv. Hojiblanca.
AB  - The oxidation of chlorophyll a (chl a) catalysed by peroxidase (POD) from
      mesocarp of the olive fruit (Olea europaea L., cv Hojiblanca) in the presence of
      H2O2 and 2,4-dichlorophenol (2,4-DCP), is characterised via the individualised
      quantification of the products of the enzymatic reaction using a new methodology
      of HPLC-UV spectrometry. This innovation has allowed the discovery that, in
      addition to 13(2) OH chl a and 15(1) OH lactone chl a, which are the first
      products of POD on chl a, the reaction process sequentially creates another
      series of oxidised chlorophyll derivatives which have not been previously
      described. Their origins have been linked to POD activity in the presence of 2,4
      DCP. Likewise, a study of the effect of the concentration of the various
      cosubstrates on the POD reaction rate demonstrated that the correct establishment
      of the relative concentrations of the same ([H2O2]/[2,4-DCP]/[Chl]=1:3:0.02) is
      crucial to explaining inhibition effects by substrates and carrying out optimum
      measurements. Therefore, new essential parameters for the determination of POD
      activity on a chlorophyll substrate are established.

PMID- 23561175
TI  - Oil composition and characterisation of phenolic compounds of Opuntia ficus
      indica seeds.
AB  - The seed composition of four varieties of Opuntia ficus-indica growing in Algeria
      was investigated. Seeds ground into a fine powder were first, subjected to oil
      extraction and fatty acids analysis. The phenolic compounds were then extracted
      from the defatted powder of seeds in order to be quantified and characterised by
      liquid chromatography coupled to mass spectrometry (LC-MS(n)) and to nuclear
      magnetic resonance (LC-NMR) approaches. In addition, an evaluation of the
      antioxidant activity of the phenolic extracts was investigated. Gas
      chromatography analysis of the seed oil showed high percentages of linoleic acid
      in the four varieties ranging from 58% to 63%. The phenolic profile of the
      Opuntia ficus-indica seeds displayed a high complexity, with more than 20
      compounds detected at 330 nm after the LC separation. Among them, three isomers
      of feruloyl-sucrose were firmly identified and another was strongly supposed to
      be a sinapoyl-diglycoside. High correlations were found between phenolic content
      in the defatted seed extracts and their antioxidant activity. The data indicate
      that the defatted cactus seed wastes still contain various components that
      constitute a source for natural foods.

PMID- 23561176
TI  - Effect of flavonoid structure on the fluidity of model lipid membranes.
AB  - We investigated how the structural properties of (+)-catechin, (-)-epicatechin, (
      )-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG) and butylated
      hydroxytoluene (BHT) correlate with structural changes of phosphatidylcholine
      plus sphingomyelin (2.4:1) model lipid membranes. Changes were measured by
      fluorescence anisotropy, electron paramagnetic resonance, and differential
      scanning calorimetry. Two fluorophores and two spin probes were used to monitor
      membrane characteristics close to water-lipid interface and in the middle of the
      bilayer. The data obtained were correlated to the amount of bounded compounds,
      the number of H-bonds, and the topological polar surface area (TPSA) of the
      compounds. These correlations reflect the behaviours of (+)-catechin, (-)
      epicatechin, EGC, EGCG and BHT. Our results confirm that phenolics studied here
      are bounded to a membrane surface predominantly via hydrogen bonds, while BTH is
      inserted into the lipid bilayer.

PMID- 23561177
TI  - Effects of industrial processing on folate content in green vegetables.
AB  - Folates are described to be sensitive to different physical parameters such as
      heat, light, pH and leaching. Most studies on folates degradation during
      processing or cooking treatments were carried out on model solutions or
      vegetables only with thermal treatments. Our aim was to identify which steps were
      involved in folates loss in industrial processing chains, and which mechanisms
      were underlying these losses. For this, the folates contents were monitored along
      an industrial canning chain of green beans and along an industrial freezing chain
      of spinach. Folates contents decreased significantly by 25% during the washing
      step for spinach in the freezing process, and by 30% in the green beans canning
      process after sterilisation, with 20% of the initial amount being transferred
      into the covering liquid. The main mechanism involved in folate loss during both
      canning green beans and freezing spinach was leaching. Limiting the contact
      between vegetables and water or using steaming seems to be an adequate measure to
      limit folates losses during processing.

PMID- 23561178
TI  - Home conservation strategies for tomato (Solanum lycopersicum): storage
      temperature vs. duration--is there a compromise for better aroma preservation?
AB  - Expression of dissatisfaction with tomato aroma prompted us to lead this study on
      the impact of domestic storage conditions on volatile compounds. Two storage
      modalities (20 and 4 degrees C) and two cultivars (Levovil and LCx) were used.
      Volatile compounds were analysed by gas chromatography-mass spectrometry
      detection after accelerated solvent extraction. Physical characteristics,
      lipoxygenase activity, hydroperoxide lyase activity; linoleic acid and linolenic
      acid were monitored. Storing tomatoes at 4 degrees C induced a drastic loss in
      volatiles, whatever their biosynthetic origin. After 30 days at 4 degrees C, the
      concentration of volatiles had decreased by 66%. Reconditioning for 24 h at 20
      degrees C was able to recover some aroma production after up to 6 days storage at
      4 degrees C. Volatile degradation products arising from carotenoids and amino
      acids increased when tomatoes were kept at 20 degrees C, while lipid degradation
      products did not vary. Storing tomatoes at fridge temperature, even for short
      durations, was detrimental for their aroma. This should be taken into account to
      formulate practical advice for consumers.

PMID- 23561180
TI  - Identification and quantification of active alkaloids in Catharanthus roseus by
      liquid chromatography-ion trap mass spectrometry.
AB  - Catharanthus roseus is an important dicotyledonous medicinal plant that produces
      anticancer compounds. The active alkaloids vinblastine, vindoline, ajmalicine,
      catharanthine, and vinleurosine were identified by direct-injection ion trap-mass
      spectrometry (IT-MS) for collecting MS(1-2) spectra. The determinations of five
      alkaloids were accomplished by liquid chromatography (LC) with UV and MS
      detections. 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 vinblastine, vindoline, ajmalicine, catharanthine, and
      vinleurosine were m/z 825->807, 457->397, 353->144, 337->144 and 809->748 by LC
      IT-MS, respectively. Two methods were used to evaluate a number of validation
      characteristics (repeatability, LOD, calibration range, and recovery). MS
      provided a high selectivity and sensitivity for determination of five alkaloids
      in positive mode. After optimisation of the methods, separation, identification
      and quantification of the five components in C. roseus were comprehensively
      accomplished by HPLC with UV and MS detection.

PMID- 23561179
TI  - Inhibition kinetics of lipid oxidation of model foods by using antioxidant
      extract of fermented soybeans.
AB  - Fermentation by using Aspergillus oryzae has been reported to increase
      antioxidant activity of soybeans significantly. The effectiveness of the extract
      from fermented soybeans was studied in 3 model foods with different complexities,
      i.e., linoleic acid emulsion, sunflower oil emulsions and bulk sunflower oil. For
      the emulsion systems, oxidation at two different pH values (4.5 and 7) was also
      compared. A reparameterised logistic equation was used to describe and to predict
      the experimental data. In general, a good agreement between experimental trends
      and simulated data from the model was found. A crude antioxidant extract (5 mg/g)
      showed a comparable antioxidant activity to 0.26 mg/g of butylated hydroxytoluene
      (BHT) in the linoleic acid emulsions. The extract exhibited a better capability
      to retard primary products in the linoleic acid systems than the secondary
      products. The opposite effect was observed in the bulk sunflower oil and its
      emulsion systems.

PMID- 23561181
TI  - A dipeptide and an amino acid present in whey protein hydrolysate increase
      translocation of GLUT-4 to the plasma membrane in Wistar rats.
AB  - Whey protein hydrolysate (WPH) is capable of increasing muscle glycogen reserves
      and of concentrating the glucose transporter in the plasma membrane (PM). The
      objective of this study was to determine which WPH components could modulate
      translocation of the glucose transporter GLUT-4 to the PM of animal skeletal
      muscle. Forty-nine animals were divided into 7 groups (n=7) and received by oral
      gavage 30% glucose plus 0.55 g/kg body mass of the following WPH components: (a)
      control; (b) WPH; (c) L-isoleucine; (d) L-leucine; (e) L-leucine plus L
      isoleucine; (f) L-isoleucyl-L-leucine dipeptide; (g) L-leucyl-L-isoleucine
      dipeptide. After receiving these solutions, the animals were sacrificed and the
      GLUT-4 analysed by western blot. Additionally, glycogen, glycaemia, insulin and
      free amino acids were also determined by standard methods. Of the WPH components
      tested, the amino acid L-isoleucine and the peptide L-leucyl-L-isoleucine showed
      greater efficiency in translocating GLUT-4 to the PM and of increasing glucose
      capture by skeletal muscle.

PMID- 23561182
TI  - Antioxidant, free radical scavenging and liver protective effects of friedelin
      isolated from Azima tetracantha Lam. leaves.
AB  - The aim of the present study was to evaluate the antioxidant, free radical
      scavenging and liver protective effects of friedelin isolated from Azima
      tetracantha Lam. leaves. In in vitro antioxidant study, the free radical
      scavenging effect of friedelin on 2,2-diphenyl-picrylhydrazyl (DPPH), hydroxyl,
      nitric oxide and superoxide radicals were evaluated. Friedelin showed very good
      scavenging effect on DPPH (IC50 21.1 mM), hydroxyl (IC50 19.8 mM), nitric oxide
      (IC50 22.1 mM) and superoxide (IC50 21.9 mM) radicals. Friedelin also showed
      strong suppressive effect on lipid peroxidation. In in vivo antioxidant study,
      CCl4 induced oxidative stress on rats produced significant increase in serum
      glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase
      (SGPT) and lactate dehydrogenase (LDH) levels along with reduction in liver
      superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and
      glutathione peroxidase (GPx) levels. Pre-treatment of rats with friedelin at 40
      mg/kg for 7 days restored these levels to normality and showed liver protection,
      comparable to the standard, silymarin (25 mg/kg). These results clearly
      demonstrated that friedelin possessed marked antioxidant and liver protective
      effects.

PMID- 23561183
TI  - High performance thin layer chromatography-densitometry: a step further for
      quality control of cranberry extracts.
AB  - A method for selective quantitation of catechin, proanthocyanidin (PAC) A2 and
      PAC-B1 in American cranberry (Vaccinium macrocarpon) extracts using high
      performance thin layer chromatography (HPTLC)-densitometry is presented.
      Methylene chloride/ethyl acetate/formic acid (6:10:1, v/v) as the mobile phase
      and 1% vanillin hydrochloric solution as staining reagent were used. In these
      conditions, three standards considered as quality markers, catechin, PAC-A2 and
      PAC-B1, were well resolved allowing simultaneous quantitation on one plate. All
      standards were quantified in the range of 0.7-5 MUg with RSD of repeatability and
      intermediate precision not exceeding 5%. Catechin, PAC-A2 and PAC-B1 profiles of
      cranberry extracts were analysed regarding global PAC amounts obtained by BL-DMAC
      assay. It appears clearly that HPTLC-densitometry process provides additional
      information which, combined with BL-DMAC results, allows qualitative and
      quantitative control of cranberry extracts. Particularly, densitometric assay
      highlighted degradation of PACs in a 7 day-extract, leading to high
      overestimation with BL-DMAC protocol.

PMID- 23561184
TI  - In vitro bioavailability of total selenium and selenium species from seafood.
AB  - In vitro bioavailability of total selenium and selenium species from different
      raw seafood has been assessed by using a simulated gastric and intestinal
      digestion/dialysis method. Inductively coupled plasma-mass spectrometry (ICP-MS)
      was used to assess total selenium contents after a microwave assisted acid
      digestion, and also to quantify total selenium in the dialyzable and non
      dialyzable fractions. Selenium speciation in the dialyzates was assessed by high
      performance liquid chromatography (HPLC) coupled with ICP-MS detection. Major Se
      species (selenium methionine and oxidized selenium methionine) from dialyzate
      were identified and characterized by HPLC coupled to mass spectrometry (HPLC-MS).
      Selenocystine was detected at low concentrations while Se-(Methyl)selenocysteine
      and inorganic selenium species (selenite and selenate) were not detected in the
      dialyzate. Low bioavailability percentages for total selenium (6.69+/-3.39 and
      5.45+/-2.44% for fish and mollusk samples, respectively) were obtained. Similar
      bioavailability percentages was achieved for total selenium as a sum of selenium
      species (selenocystine plus oxidized selenium methionine and selenium methionine,
      mainly). HPLC-MS data confirmed SeMet oxidation during the in vitro procedure.

PMID- 23561185
TI  - Modulating beta-carotene bioaccessibility by controlling oil composition and
      concentration in edible nanoemulsions.
AB  - Diets rich in carotenoids have been correlated with a reduced risk of developing
      certain types of chronic diseases, but these bioactive components have low
      intestinal absorption due to their hydrophobic nature. The aim of this work was
      to study the effect of carrier oil composition (medium-chain triglyceride (MCT)
      to long-chain triglyceride (LCT) ratio) and total carrier oil concentration (1%
      or 4% w/w) on the physical stability, lipid digestibility and bioaccessibility of
      beta-carotene-loaded nanoemulsions, using a simulated digestion process.
      Lipolysis led to an appreciable increase in the size and negative charge on the
      particles in the system. The total fraction of triacylglycerols converted to free
      fatty acids decreased as the percentage of LCT within the lipid phase increased,
      particularly for the nanoemulsions with higher fat contents. There was an
      increase in beta-carotene bioaccessibility as the LCT within the lipid phase
      increased for low fat nanoemulsions, which was attributed to the increased
      solubilisation capacity of mixed micelles formed by LCT. beta-carotene
      bioaccessibility showed a complex relationship on LCT content for high fat
      nanoemulsions, due to the opposing effects of lipid digestion and micelle
      solubilisation. These results may facilitate the optimisation of delivery systems
      for lipophilic bioactive compounds for food or pharmaceutical applications.

PMID- 23561186
TI  - Structures and reactions of compounds involved in pink discolouration of onion.
AB  - In "pinking" of onion, E-(+)-S-(1-propenyl)-L-cysteine sulfoxide is first cleaved
      by alliinase to yield colour developers (CDs), which react with amino acids, such
      as valine, to form pigment precursors (PPs). The PPs react with naturally
      occurring carbonyls (NOCs) to form pigments. By inducing a PP from previously
      isolated cepathiolanes and L-valine, it was confirmed that cepathiolanes
      constitute at least a part of the CDs. From the PP and formaldehyde as a NOC, two
      colourless and two pink compounds were derived. The structure of one of the
      colourless compounds was established as 2-(2-(1-(1-carboxy-2-methylpropyl)-3,4
      dimethyl-1H-pyrrol-2-yl)methyl-3,4-dimethyl-1H-pyrrol-1-yl)-3-methylbutanoic
      acid. The structures of the other colourless compound and the pink pigments were
      predicted based on their molecular formula and the MS(n) spectral data. A
      trimeric pigment structure was predicted for one of the pink pigments, which was
      believed to be the first to be reported in the literature. With these, a new
      reaction scheme for "pinking" of onion is proposed.

PMID- 23561187
TI  - Oregon 'Pinot noir' grape anthocyanin enhancement by early leaf removal.
AB  - Complete cluster zone leaf removal of 'Pinot noir' was initiated at three
      separate pre-veraison growth stages (bloom, grain-pea size, and bunch closure)
      and maintained leaf free until harvest, for four growing seasons (2008-2011).
      Fruit anthocyanin composition was examined at harvest for the last two vintages
      (2010 and 2011) and compared to a control-no cluster zone leaf removal.
      Experiments were conducted at two commercially operating Oregon vineyards (site
      A=420 rootstock/'Pinot noir' 115 scion and site B=3309C rootstock/'Pinot noir'
      777 scion). All clusters contained the five anthocyanins typically found in
      'Pinot noir'. Leaf removal at bloom and maintained until harvest produced maximum
      anthocyanin accumulation in 'Pinot noir' grapes (site A=85.24 mg/100 g and site
      B=125.06 mg/100 g), compared to no leaf removal (control; site A=57.91 mg/100 g
      and site B=97.56 mg/100 g). Even leaf removal at bunch closure (last leaf removal
      initiation period) increased grape anthocyanin (site A=73.22 mg/100 g and site
      B=118.93 mg/100 g) compared to control, but total anthocyanins were lower than
      grapes from bloom leaf removal (first time period). Results differed slightly by
      vineyard site and rootstock/scion combination.

PMID- 23561188
TI  - Antibacterial activity-guided purification and identification of a novel C-20
      oxygenated ent-kaurane from Rabdosia serra (MAXIM.) HARA.
AB  - The objective of this work was to conduct an activity-guided isolation of
      antibacterial compounds from Rabdosia serra. The ethanol extracts of R. serra
      leaf and stem were partitioned sequentially into petroleum ether, ethyl acetate,
      butanol and water fractions, respectively. The ethanol extract of leaf evidenced
      broad-spectrum antibacterial activity against gram-positive bacterial, including
      Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Listeria
      monocytogenes. The ethyl acetate fractions of leaf and stem exhibited strong
      inhibition against gram-positive bacteria, and were then purified further. On the
      basis of antibacterial assay-guided purification, three phenolic compounds
      (rosmarinic acid, methyl rosmarinate and pedalitin) and four C-20 oxygenated ent
      kauranes (effusanin E, lasiodin, rabdosichuanin D and a new compound namely
      effusanin F) were obtained, whose contents were determined by HPLC analysis. The
      broth microdilution method confirmed the important inhibition potential of C-20
      oxygenated ent-kauranes with low minimum inhibitory concentration (MIC) values.
      Effusanin E, lasiodin and effusanin F could be useful for the development of new
      antibacterial agents.

PMID- 23561189
TI  - Inhibitory effects of myricetin on mammalian DNA polymerase, topoisomerase and
      human cancer cell proliferation.
AB  - In this study, the inhibitory activities against mammalian DNA polymerases (pols)
      of 16 major bioflavonoids were investigated. Myricetin (3,3',4',5,5',7
      hexahydroxyflavone) was the most potent inhibitor of pols amongst the compounds
      tested, with IC50 values of 21.3-40.9 MUM. This compound did not affect the
      activities of plant (cauliflower) pol alpha or prokaryotic pols. Myricetin also
      inhibited human DNA topoisomerase II (topo II) activity with an IC50 value of
      27.5 MUM, but did not inhibit the activities of other DNA metabolic enzymes
      tested. Myricetin also did not influence the direct binding to double stranded
      DNA as determined by thermal transition analysis. It was found to prevent the
      proliferation of human colon HCT116 carcinoma cells with an LD50 of 28.2 MUM,
      halt the cell cycle in G2/M phase, and induce apoptosis. These results suggest
      that the decrease of proliferation may be a result of the inhibition of cellular
      topoisomerase (topo) II rather than pols.

PMID- 23561190
TI  - Preparative separation of triterpene alcohol ferulates from rice bran oil using a
      high performance counter-current chromatography.
AB  - A novel method for the separation of two major triterpene alcohol ferulates from
      rice bran oil (RBO) was developed using a high performance counter-current
      chromatography (HPCCC). A two-phase solvent system of n-hexane-acetonitrile (1:1,
      v/v) was applied to purify cycloartenyl ferulate (CAF) and 24-methylene
      cycloartanyl ferulate (24-mCAF) from RBO. The yields were 20.50+/-2.60 mg CAF and
      12.62+/-1.15 mg 24-mCAF from 390 mg RBO through a two-step separation procedure.
      The purities of the two compounds were 97.97+/-0.90% and 95.50+/-0.75%,
      respectively, as determined by high performance liquid chromatography (HPLC).
      Their chemical structures were confirmed by ultra performance liquid
      chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and
      (1)H, (13)C and 2D nuclear magnetic resonance (NMR). This represents the first
      report on direct separation of CAF and 24-mCAF from RBO by HPCCC.

PMID- 23561191
TI  - Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and
      beta-oxidation: a proof of concept study.
AB  - Alkylresorcinols (AR) are phenolic lipids present in the bran of some cereals. AR
      may serve as a biomarker for whole grain wheat and rye intake. While AR
      pharmacokinetics and two major metabolites have been reported, the metabolic
      pathways contributing to their relatively rapid elimination from the circulation
      remain to be speculative. In this study, we investigated if omega- and beta
      oxidation mediate catabolism of the AR homologue C19:0 to form 3,5
      dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), using
      3 in vitro platforms, human cytochrome P450 4F2 (CYP4F2), human liver S9, and
      HepG2 cells. One hydroxylated C19:0 metabolite was formed by CYP4F2 and one
      hydroxylated and one carboxylated C19:0 were tentatively identified after
      incubation of AR with S9. The formation of DHPPA was quantifiable when HepG2
      cells were treated with C19:0 for 48 h. Our results are consistent with a
      metabolic pathway by which AR are degraded to phenolic acids via CYP4F2-mediated
      omega-oxidation and subsequent beta-oxidation.

PMID- 23561192
TI  - Modifications of Kyoho grape berry quality under long-term NaCl treatment.
AB  - Different concentrations of a sodium chloride spray were applied to the grapevine
      cultivar Kyoho to determine the effects of salinity on berry quality. The fruit's
      fresh weight, relative water content, hardness and titratable acid were gradually
      enhanced with increased salt concentrations. Anthocyanin and soluble solids
      increased after treatment with moderate salinity (20 and 60 mM); however, the
      results were reversed under high salinity (100 and 150 mM). The soluble sugars
      glucose, fructose and sucrose increased after treatment with moderate salinity,
      whereas glucose and fructose declined under high salinity. For the six organic
      acids tested, their total levels were elevated by salinity, which increased the
      production of tartaric and malic acids. The aroma of the berry was extremely
      sensitive to salinity and showed a considerable decline in abundance and variety
      at 20 mM NaCl. In summary, moderate salinity enhanced the overall berry quality,
      but decreased the aroma quality, whereas high salinity decreased the berry
      quality.

PMID- 23561193
TI  - Effect of floral sources on the antioxidant, antimicrobial, and anti-inflammatory
      activities of honeys in Taiwan.
AB  - We evaluated the antioxidant, antibacterial, and anti-inflammatory activities of
      honey made from different floral sources, including the medicinal herb Bidens
      pilosa, fruit trees, Dimocarpus longan, Litchi chinensis, and Citrus maxima, the
      Taiwanese endemic plant Aglaia formosana, and a multifloral forest. The total
      phenolic and flavonoid contents of the honey made from B. pilosa were
      significantly higher than those of the other honeys. The honey from B. pilosa
      also had significantly greater scavenging activities for 1,1-diphenyl-2
      picrylhydrazyl (DPPH.) and hydroxyl radical, and substantially more reducing
      power. In addition, the honey from B. pilosa showed greater antibacterial
      activity against gram-positive and gram-negative bacteria. However, B. pilosa
      honey showed little inhibitory activity against IL-8 secretion, whereas the other
      honeys did. These findings suggest that the levels of antioxidant and
      antibacterial activities are attributable to the total phenolic and flavonoid
      contents of honeys, while the IL-8 inhibition is attributable to components other
      than phenols.

PMID- 23561194
TI  - The impact of Ca2+ combination with organic acids on green tea infusions.
AB  - The effect of Ca(2+) in brewing water on the organic acid content, turbidity, and
      formation of tea cream and sediment in green tea infusions was studied. When the
      Ca(2+) concentration of the brewing water was >40 mg L(-1), the green tea
      infusion became more turbid. The turbidity of the tea infusion was highly
      negatively correlated with the contents of oxalic acid (R=-0.89, p<0.01), quinic
      acid (R=-0.90, p<0.01) and tartaric acid (R=-0.82, p<0.01). Oxalic acid on its
      own interacted with Ca(2+) at low concentrations, whereas polyphenols and protein
      did not. In conclusion, Ca(2+) in brewing water influences the quality of a tea
      infusion by inducing tea cream and sediment formation from combination of Ca(2+)
      and organic acids, such as oxalic acid, quinic acid and tartaric acid. Ca(2+) and
      oxalate are the main metal ion and anion, respectively, involved in tea cream and
      sediment formation on tea infusion cooling or concentrating.

PMID- 23561195
TI  - Extra virgin olive oil bitterness evaluation by sensory and chemical analyses.
AB  - An experimental investigation was performed on blend extra virgin olive oils
      (EVOOs) from different cultivars and EVOO from different olive monovarieties
      (Coratina, Leccino, Maiatica, Ogliarola) with the aim to evaluate the possibility
      of estimating the perceived bitterness intensity by using chemical indices, such
      as the total phenol content and the compounds responsible for oil bitterness
      measured spectrophotometrically at 225 nm (K225 value), as bitterness predictors
      in different EVOO. Therefore, a bitterness predictive model, based on the
      relationship between the perceived bitterness intensity of the selected stimuli
      and the chosen chemicals parameters has been built and validated. The results
      indicated that the oil bitterness intensity could be satisfactorily predicted by
      using the K225 values of oil samples.

PMID- 23561196
TI  - Polycyclic aromatic hydrocarbons (PAH) and phenolic substances in meat products
      smoked with different types of wood and smoking spices.
AB  - The contents of polycyclic aromatic hydrocarbons (15+1 EU PAH) and phenolic
      substances (guaiacol, 4-methylguaiacol, syringol, eugenol, and trans-isoeugenol)
      were investigated in smouldering-smoked Frankfurters and mini-salamis. For the 51
      smoking experiments wood chips of oak, poplar, hickory, spruce, fir, alder,
      beech, and beech with an apple-smoking spice mix, cherry-smoking spice mix, and a
      mix of juniper berries and bay leaves were tested. The use of poplar and hickory
      led to a decrease in the PAH contents in the range of 35-55% compared to the
      commonly used beech wood. Higher PAH contents by using softwood were not
      observed. The use of the rapidly growing poplar seems to be a reasonable approach
      for reducing the PAH contents in smoked meat products. Furthermore, the sum
      contents of the five phenolic substances in sausages smoked with poplar were
      higher, or only slightly lower, when compared to the use of beech.

PMID- 23561197
TI  - Development of electrochemical biosensor with nano-interface for xanthine sensing
      -a novel approach for fish freshness estimation.
AB  - Highly sensitive, selective and mediator-free electrochemical biosensor with nano
      interface for sensing xanthine using xanthine oxidase (XOx) has been developed.
      Towards the preparation of nano-interface, Fe3O4 nanoparticles were synthesized
      by thermal co-precipitation method and structural, morphological
      characterizations were carried out using X-ray diffraction (XRD), field emission
      scanning electron microscope (FE-SEM) and field emission transmission electron
      microscope (FE-TEM) respectively. The modified electrode with the covalently
      linked XOx was confirmed by FT-IR. With the modified electrode as working
      electrode, electrochemical studies were carried out. The linear range was found
      to be from 0.4 to 2.4 nM. The biosensor exhibited an optimum response in less
      than 2 s and was not prone to interferences from ascorbic acid, urea and sucrose.
      The Michaelis-Menten constant (Km) was found to be 1.3 nM. The limit of detection
      is found to be 2.5 pM and limit of quantification as 8.3 pM. The developed
      biosensor was used for the real time measurement of fish freshness.

PMID- 23561198
TI  - Cultivating conditions effects on kefiran production by the mixed culture of
      lactic acid bacteria imbedded within kefir grains.
AB  - The influence of fermentation temperature, agitation rate, and additions of
      carbon sources, nitrogen sources, vitamins and minerals on production of kefiran
      by kefir grains lactic acid bacteria was studied in a series of experiments. The
      main aim of the work was to increase the exopolysaccharide (EPS) production where
      customised milk was used as fermentation medium. It was proved that the
      controlling of culturing conditions and the modifying of fermentation medium
      conditions (i.e., carbon, nitrogen, mineral sources and vitamins) can
      dramatically enhance the production of the EPS. The temperature and agitation
      rate were critical for kefiran production during the 24 h cultivation of grains;
      our optimised conditions being 25 degrees C and 80 rpm, respectively. In
      addition, when optimising the effects of additional nutrition, it was found that
      5% (w/v) lactose, 0.1% (w/v) thiamine, and 0.1% (w/v) FeCl3 led to the maximal
      production of EPS. The results indicate that nutrients can be utilised to improve
      the production of EPS and that good kefir grains growth does not appear to be a
      determining factor for a high production yield of EPS.

PMID- 23561199
TI  - A Rapid tool for the stability assessment of natural food colours.
AB  - Natural food colours lack stability under a number of conditions such as pH
      variation, oxidation, hydration, heat treatment and, most importantly, exposure
      to daylight. Stability tests to assess shelf life of natural colours under light
      irradiation can be time consuming. Thus, an accelerated test carried out under
      high light intensity irradiation that can be related to normal daylight
      irradiation conditions is highly desirable. Samples of various natural colouring
      solutions were prepared in aqueous model matrices at a range of pH values to
      mimic the majority of food matrices, pasteurised and irradiated under normal D65
      light (0.2 W/m(2)) at 25 degrees C, and in parallel under high light intensity
      irradiation (30 W/m(2)) at 3 different temperatures (25, 35 and 45 degrees C).
      Similarly to the already known Q10 parameters for temperature, acceleration
      factors QL for irradiation, were determined and used for the first time to obtain
      a link between colour degradation under normal and accelerated conditions. It was
      possible, using these acceleration factors, to greatly reduce the time required
      to predict and compare the shelf life stability for a series of natural colours
      in aqueous model systems.

PMID- 23561200
TI  - Fatty acid profiling of the seed oils of some varieties of field peas (Pisum
      sativum) by RP-LC/ESI-MS/MS: towards the development of an oilseed pea.
AB  - Reversed-phase liquid chromatography coupled to negative-ion electrospray tandem
      mass spectrometry (RP-LC/ESI-MS/MS) was used to study the fatty acid profile from
      the oil of harvested field pea (Pisum sativum) varieties as part of a research
      project to develop this legume as a commercial oilseed for Canada. The seed oils
      from pea samples contained palmitic and stearic acids as major saturated fatty
      acids. Oleic, linoleic and linolenic acids were the major unsaturated fatty acids
      found. Small percentages of other long chain fatty acids were also detected. This
      profile suggests that the species of field pea investigated might have the
      potential to be used as raw materials to develop a future new oilseed crop for
      the food industry. Fatty acid extracts did not require further manipulation
      before final analysis by RP-LC/ESI-MS/MS, indicating the utility and relative
      simplicity of this technique for future screening studies.

PMID- 23561201
TI  - Antihypertensive effects of lactoferrin hydrolyzates: Inhibition of angiotensin-
      and endothelin-converting enzymes.
AB  - The potential of bovine lactoferrin (LF) as a source of antihypertensive peptides
      acting on the renin-angiotensin system (RAS) and the endothelin (ET) system as
      dual vasopeptidase inhibitors has been examined. For this purpose enzymatic LF
      hydrolyzates (LFHs) were generated by trypsin and proteinase K digestions.
      Permeate fractions with molecular masses lower than 3 kDa (LFH <3 kDa) were
      orally administered to spontaneously hypertensive rats (SHRs). Although both LFHs
      <3 kDa showed in vitro angiotensin I-converting enzyme (ACE)-inhibitory activity,
      only proteinase K LFH <3 kDa exerted an in vivo antihypertensive effect. The
      proteinase K LFH <3 kDa and a previously characterized pepsin LFH <3 kDa with ACE
      inhibitory and antihypertensive effects were tested in ex vivo functional assays
      as inhibitors of ACE-dependent vasoconstriction. Pepsin LFH <3 kDa but not
      proteinase K LFH <3 kDa inhibited ACE-dependent vasoconstriction. When tested as
      inhibitors towards endothelin-converting enzyme (ECE), both LFHs <3 kDa exerted
      in vitro inhibitory effects on ECE activity and inhibited ECE-dependent
      vasoconstriction. Most abundant peptides in proteinase K LFH <3 kDa were
      identified by using an ion trap mass spectrometer. Based on peptide abundance,
      two peptides (GILRPY and REPYFGY) were chemically synthesized and their ECE
      inhibitory activity was tested. Both exerted in vitro inhibitory effects on ECE
      activity. In conclusion, orally effective antihypertensive LFHs <3 kDa may act as
      dual vasopeptidase (ACE/ECE) or as single ECE inhibitors with different
      antivasoconstrictor effects depending on the protease used to release bioactive
      peptide sequences.

PMID- 23561202
TI  - Tert-butylhydroquinone recognition of molecular imprinting electrochemical sensor
      based on core-shell nanoparticles.
AB  - One novel electrochemistry-molecular imprinting sensor for determining tert
      butylhydroquinone (TBHQ) in foodstuff was developed. TBHQ-imprinted core-shell
      nanoparticles (TICSNs) were fabricated using silica nanoparticles as core
      material. The silica nanoparticles were modified with (3-chloropropyl)
      trimethoxysilan and polyethylenimine, respectively, and polymerised to form the
      TICSNs with ethylene glycol dimethacrylate as cross-linker. The specific core
      shell structure demonstrates extremely high specific surface area which greatly
      increases the effective binding sites and improves the recognition capability for
      model molecules. Under the optimal conditions, the linear range of the
      calibration curve was 0.1-50.0 mg kg(-1) with the detection limit of 0.27 mg kg(
      1). The sensor has been successfully applied to the determination of TBHQ in food
      samples and achieved high sensitivity and selectivity.

PMID- 23561203
TI  - A micellar improved method for trace levels selenium quantification in food
      samples, alcoholic and nonalcoholic beverages through CPE/FAAS.
AB  - A useful preconcentration and determination method was proposed for trace
      selenium in food samples. The procedure is based on complex formation of Pyronine
      B with Se(IV) ions in the presence of sodium dodecyl sulphate (SDS) and Ponpe
      7.5. The variables affecting complex formation, extraction and phase separation
      were studied and optimised. Under the experimental conditions used, the
      calibration graph was linear in the range of 20-1700 MUg L(-1) for Se(IV) ions.
      The limit of detection was 3.81 MUg L(-1) of Se(IV) and the relative standard
      deviation for 5 replicate determinations at 250 MUg L(-1) concentration level was
      2.45%. Recovery values were obtained between 97.8% and 102.8% for spiked samples.
      The method was successfully applied to the determination of total selenium in
      some food samples and alcoholic and nonalcoholic beverages. Its validity was
      checked by the analysis of four certified reference materials. The results
      obtained by the proposed method were quantitatively in good agreement with the
      certified values.

PMID- 23561204
TI  - Inhibitory effects of water extract of Flos Inulae on mutation and tyrosinase.
AB  - In this study, the effects of a water extract of Flos Inulae (WFI) on
      antioxidant, antimutation and antityrosinase were investigated. The results
      showed that WFI inhibited the mutagenicity of 2-aminoanthracene (2-AA), an
      indirect mutagen; and 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen toward
      Salmonella typhimurium TA 98 and TA 100. In addition, WFI, in the range of 0.2
      0.6 mg/ml, showed radical scavenging, reducing activities and chelating activity
      as well as decreased lipid oxidative damage. Meanwhile, WFI also inhibited
      tyrosinase activity and NO generation in lipopolysaccharide (LPS) stimulated
      macrophages. High performance liquid chromatography analysis suggests that the
      major phenolic constituents in WFI are chlorogenic acid, rutin, quercetin,
      luteolin and kaempferol. These bioactive components may contribute to the
      protective effects of WFI. The obtained data suggests that Flos Inulae can be
      applied to antimutation, antityrosinase and anti-inflammation.

PMID- 23561205
TI  - Curcumin inhibits invasion and metastasis in K1 papillary thyroid cancer cells.
AB  - Curcumin, the active constituent of dietary spice turmeric, possesses a strong
      potential for cancer prevention and treatment. However, there is no study to
      address the effects of curcumin on invasion and metastasis of thyroid cancers.
      Thyroid cancer is the most common malignancy of endocrine organs, and its
      incidence rates have steadily increased over recent decades. Although most
      indolent tumours can be effectively managed, metastatic tumours at distant
      secondary sites behave aggressively and currently there is no effective form of
      treatment. Here, for the first time it has been reported that curcumin inhibit
      multiple metastasis steps of K1 papillary thyroid cancer cells. Curcumin dose
      dependently suppressed viability of K1 cells as well as its cell attachment,
      spreading, migration and invasion abilities. Moreover, curcumin could also down
      regulate the expression and activity of matrix metalloproteinase-9 (MMP-9). The
      findings showed that curcumin might be an effective tumouristatic agent for the
      treatment of aggressive papillary thyroid carcinomas.

PMID- 23561206
TI  - A fast, reliable, ultra high performance liquid chromatography method for the
      simultaneous determination of amino acids, biogenic amines and ammonium ions in
      cheese, using diethyl ethoxymethylenemalonate as a derivatising agent.
AB  - Derivatisation treatment with diethyl ethoxymethylenemalonate followed by ultra
      HPLC allowed the simultaneous quantification of 22 amino acids, 7 biogenic amines
      and ammonium ions in cheese samples in under 10 min. This is the fastest elution
      time ever reported for such a resolution. The proposed method shows good
      linearity (R(2)>0.995) and sensitivity (detection limit 0.08-3.91 MUM;
      quantification limit <13.02 MUM). Intra- and inter-day repeatability ranged from
      0.35% to 1.25% and from 0.85% to 5.2%, respectively. No significant effect of the
      cheese matrix was observed.

PMID- 23561207
TI  - The potential of solvent-minimized extraction methods in the determination of
      polycyclic aromatic hydrocarbons in fish oils.
AB  - Fish oil has been identified as one of the most important contributors to the
      level of Persistent Organic Pollutants (POPs) in feed products. The determination
      of polycyclic aromatic hydrocarbons (PAHs) in fish oils is complicated due to the
      fat matrix, which affects both extraction efficiency and analytical quality. This
      article reviews and addresses two of the most relevant analytical methods for
      determining 11 mutagenic and carcinogenic PAHs, as well as two EPA indicator PAHs
      in fish oils. We discuss and critically evaluate two different extraction
      procedures, such as ultrasound-assisted solvent extraction (USAE) and ultrasound
      assisted emulsification-microextraction (USAEME). Clean-up of extracts was
      performed by solid-phase extraction using C18 and glass columns containing silica
      gel and florisil for USAE or only C18 for USAEME. Detection of the selected PAHs
      was carried out by high-performance liquid chromatography coupled with
      fluorescence detection for determination. Optimization of the variables affecting
      extraction by the selected extraction techniques was conducted and recoveries
      ranged from 70% to 100% by USAE and from 70% to 108% by USAEME with estimated
      quantification limits between 0.020 and 2.6 MUg/kg were achieved. Moreover, the
      applicability of the selected methods was evaluated by the analysis of real
      samples. To our knowledge, this is the first time that USAEME has been applied to
      the determination of PAHs in food matrices, such as oil fish samples. The methods
      proposed were applied to the determination of the target PAHs in fish samples
      from different countries, and it was found that the low PAH contamination of the
      selected fish oils could mainly occur by atmospheric sources.

PMID- 23561208
TI  - Effect of Saccharomyces strains on the quality of red wines aged on lees.
AB  - Ageing on lees involves ageing the wine in contact with yeast cells after
      fermentation. If combined with the addition of oak chips, it can soften the wood
      flavour and increase the aromatic complexity of wine. The aim of the present work
      is to optimise both ageing techniques through selection of an adequate
      Saccharomyces cerevisiae strain. The study lasted 6 months and content of
      polysaccharides, anthocyanins, proanthocyanidins, volatile compounds, colour
      parameters and sensory analysis, were periodically evaluated. Among the strains
      tested, G37 showed the highest release of polysaccharides (24.4+/-5.5 mg l(-1)).
      Vanillin, syringaldehyde and furfuryl alcohol increased with ageing time in 7VA2
      treatment. The wine aged with CTPL14 strain presented fewer monomeric and
      oligomeric proanthocyanidins (12.4+/-0.6 and 83.4+/-8.3 mg l(-1), respectively),
      and showed the lowest astringency and bitterness sensations. Results show an
      improvement in the sensory profile of the red wine aged with a combination of
      these two techniques.

PMID- 23561209
TI  - Evolution of the aromatic profile in Garnacha Tintorera grapes during raisining
      and comparison with that of the naturally sweet wine obtained.
AB  - The postharvest dehydration is one of the most important steps in obtaining a
      high quality naturally sweet wine and it can play an important role in modulating
      the production and the release of volatile compounds. However, only a few studies
      have analysed the changes in the free and bound volatile compounds of grapes
      throughout the process. In this work, GC-MS was applied to determine the aromatic
      composition of Garnacha Tintorera grapes subjected to off-vine dehydration or
      raisining at several points during the process. The total water loss in 83 days
      was about 62% and the sugar concentration rose from 225 to 464 g/L. Within the
      free volatile compounds, isoamyl alcohols, benzaldehyde and guaiacol registered
      the largest increase above the concentration effect due to water loss; while
      within the bound volatile compounds were isoamyl alcohols, ethyl vanillate and
      benzoic acid. The aromatic profile of the raisins obtained were mainly
      caramelised, floral, phenolic and burned.

PMID- 23561210
TI  - Non-enzymatic glycation of natural actomyosin (NAM) with glucosamine in a liquid
      system at moderate temperatures.
AB  - Muscle protein functionality plays an important role in routine applications in
      the food industry. Glycation by the Maillard reaction is a naturally occurring
      process, which can be used to develop new ingredients with improved functionality
      using a food grade approach. Actomyosin was conjugated with glucose or
      glucosamine in a liquid system at moderate temperatures (40 degrees C). Sugar to
      protein conjugation was evident by UV-Vis spectral changes, with the glycation
      level determined by matrix assisted laser desorption/ionisation mass
      spectrometry. Parameters for glycation of muscle protein were optimised using the
      bidimensional hierarchical clustering analyses. The best glycation conditions
      were 40 degrees C for 8 h at 1:3 protein:sugar ratio. Solubility and emulsifying
      properties of glycoconjugates were significantly improved as compared to non
      glycated proteins. At pH 7 glycated actomyosin was on average 31% more soluble
      compared to non-treated protein. Glucosamine was found to be more effective for
      glycation and provided higher protein functionality as compared to glucose.

PMID- 23561211
TI  - LC-ESI-TOF-MS identification of bioactive secondary metabolites involved in the
      antioxidant, anti-inflammatory and anticancer activities of the edible halophyte
      Zygophyllum album Desf.
AB  - In this work, liquid chromatography coupled to electrospray time-of-flight mass
      spectrometry (LC-ESI-TOF-MS) has been applied to screen bioactive metabolites in
      shoot extract of the medicinal halophyte Zygophyllum album. Among 10 compounds
      identified (saponins, flavonoids and sterols) five were reported for the first
      time in Z. album. Furthermore, novel biological activities of hexane,
      dichloromethane and methanolic extracts were assessed. Results showed that
      methanolic extract exhibit the highest antioxidant activity using in vitro ORAC
      test and anti-inflammatory activity, inhibiting by 84.8% NO release in RAW264.7
      macrophages. However, dichloromethane extract proved the utmost antioxidant
      activity in cell (WS1) based-assay (IC50=57 MUg/ml) and interesting anticancer
      capacity against human lung carcinoma (A-549) and colon adenocarcinoma (DLD-1)
      cells (IC50=37 and 48 MUg/ml, respectively). These findings can be attributed to
      the presence of triterpenes, flavonoids and sterols in Z. album, which are widely
      known as powerful antioxidants and used in various industrial fields.

PMID- 23561212
TI  - Degradation of complex carbohydrate: immobilization of pectinase from Bacillus
      licheniformis KIBGE-IB21 using calcium alginate as a support.
AB  - Pectinases are heterogeneous group of enzymes that catalyse the hydrolysis of
      pectin substances which is responsible for the turbidity and undesirable
      cloudiness in fruits juices. In current study, partially purified pectinase from
      Bacillus licheniformis KIBGE-IB21 was immobilized in calcium alginate beads. The
      effect of sodium alginate and calcium chloride concentration on immobilization
      was studied and it was found that the optimal sodium alginate and calcium
      chloride concentration was 3.0% and 0.2 M, respectively. It was found that
      immobilization increases the optimal reaction time for pectin degradation from 5
      to 10 min and temperature from 45 to 55 degrees C, whereas, the optimal pH
      remained same with reference to free enzyme. Thermal stability of enzyme
      increased after immobilization and immobilized pectinase retained more than 80%
      of its initial activity after 5 days at 30 degrees C as compared with free enzyme
      which showed only 30% of residual activity. The immobilized enzyme also exhibited
      good operational stability and 65% of its initial activity was observed during
      third cycle. In term of pectinase immobilization efficiency and stability, this
      calcium alginate beads approach seemed to permit good results and can be used to
      make a bioreactor for various applications in food industries.

PMID- 23561213
TI  - Diversity of (dihydro) hydroxycinnamic acid conjugates in Colombian potato
      tubers.
AB  - In potato tuber, caffeic acid (the predominant hydroxycinnamic acid (HCA)), its
      conjugates (HCAcs; i.e. chlorogenic acid (ChA), crypto-ChA, and neo-ChA), and
      anthocyanin-linked HCAs have been extensively described in the literature. In
      contrast, only little information is available on the occurrence of other HCAcs
      and didydrohydroxycinnamic acid conjugates (DHCAcs). Fifteen Colombian potato
      cultivars were screened for these less commonly described conjugates by reversed
      phase ultrahigh performance liquid chromatography coupled to a diode array
      detector and a heated electrospray ionisation mass spectrometer. A total of 62
      HCAs/HCAcs/DHCAcs were found in extracts from peel and flesh. Among them, only
      twelve compounds were common to all cultivars in both peel and flesh. The less
      commonly described compounds accounted for 7.1-20.1% w/w of the total amount of
      HCAs/HCAcs/DHCAcs in whole tubers, highlighting their contribution to the total
      phenolic profile of potato tubers. Among all cultivars, the abundance (mg/100 g
      DW whole tuber) of neo-ChA (0.8-7.4) ranged in similar quantities as the less
      commonly reported feruloyl octopamine (1.2-5.2), 5-O-feruloyl quinic acid (0.1
      7.5), cis-ChA (1.1-2.2), caffeoyl putrescine (0.6-2.5), sinapoyl hexose (0.1
      1.8), N(1),N(14)-bis-(dihydrocaffeoyl) spermine (0.2-1.7), N(1),N(10)-bis
      (dihydrocaffeoyl) spermidine (1.1-2.6), and N(1),N(5),N(14)-tris
      (dihydrocaffeoyl) spermine (trace - 11.1).

PMID- 23561214
TI  - Influence of pH, metal chelator, free radical scavenger and interfacial
      characteristics on the oxidative stability of beta-carotene in conjugated whey
      protein-pectin stabilised emulsion.
AB  - The influence of whey protein isolate (WPI)-beet pectin conjugates formed by dry
      heating on the oxidative stability of beta-carotene in O/W emulsions was studied.
      It was mainly focused on the influence of pH, metal chelator, free radical
      scavenger and interfacial characteristics on the degradation of beta-carotene in
      the emulsion stabilised by conjugate. The conjugate increased the oxidative
      stability of beta-carotene in the emulsion as compared to their unconjugated
      mixture at pH 7.0. The desferoxamine retarded beta-carotene degradation at pH 4.0
      more effectively than pH 7.0 and more effectively in the emulsion with the
      conjugate than the unconjugated mixture (p<0.05). The addition of 200 mg/kg alpha
      tocopherol significantly improved the stability of beta-carotene in the conjugate
      stabilised emulsion. The emulsions were washed to remove conjugate not absorbed
      to the emulsion droplet interface, indicating that unabsorbed emulsifiers could
      protect beta-carotene. It suggested that WPI-pectin conjugate could be used to
      protect bioactive lipids in emulsions.

PMID- 23561215
TI  - Mechanisms of saccharide protection against epigallocatechin-3-gallate
      deterioration in aqueous solutions.
AB  - We investigated the mechanisms of the protection conferred by sugars to
      epigallocatechin-3-gallate (EGCG) against deterioration. Additionally, we present
      a rapid method for evaluating the deterioration rate of EGCG using absorbance
      spectroscopy. We found that various sugars provided different levels of
      protection at identical weight percentage, and the combination of sugars and beta
      lactoglobulin nanocomplexes provided greater protection for EGCG than each
      protective component alone. We suggest that the concentration-dependent
      protection by sugars resulted from a combination of mechanisms, including: (1)
      reduced aqueous O2 solubility, (2) scavenging of reactive oxygen species, and (3)
      chelation of traces of transition metal ions, which is suggested to be the main
      reason for the differences among the sugars. The observed protective effect of
      sugars can be easily applied by the industry in proper selection of sugars for
      enrichment of syrups or concentrates with EGCG and for the preparation of
      enriched beverages and foods for health promotion.

PMID- 23561216
TI  - Combined impact of Bacillus stearothermophilus maltogenic alpha-amylase and
      surfactants on starch pasting and gelation properties.
AB  - In baking applications involving starch gelatinisation, surfactants such as
      sodium stearoyl lactylate (SSL) and monoacylglycerols (MAG) and Bacillus
      stearothermophilus maltogenic alpha-amylase (BStA) can be used jointly. We here
      showed that SSL but not MAG delays wheat starch hydrolysis by BStA. The effects
      were explained in terms of different degrees of adsorption of the surfactants on
      the starch granule surface, retarded and/or decreased water uptake and delayed
      availability of gelatinised starch for hydrolysis by BStA. Additional experiments
      with waxy maize starch led to the conclusion that SSL impacts swelling power and
      carbohydrate leaching more by covering the starch granule surface than by forming
      amylose-lipid complexes. SSL postponed starch hydrolysis by BStA, but this did
      not influence subsequent starch gelation. Finally, when adding SSL or MAG on top
      of BStA to starch suspensions, the effect of the surfactants on gel strength
      predominated over that of BStA.

PMID- 23561217
TI  - Near infrared spectroscopy (NIRS) for on-line determination of quality parameters
      in intact olives.
AB  - The acidity, moisture and fat content in intact olive fruits were determined on
      line using a NIR diode array instrument, operating on a conveyor belt. Four sets
      of calibrations models were obtained by means of different combinations from
      samples collected during 2009-2010 and 2010-2011, using full-cross and external
      validation. Several preprocessing treatments such as derivatives and scatter
      correction were investigated by using the root mean square error of cross
      validation (RMSECV) and prediction (RMSEP), as control parameters. The results
      obtained showed RMSECV values of 2.54-3.26 for moisture, 2.35-2.71 for fat
      content and 2.50-3.26 for acidity parameters, depending on the calibration model
      developed. Calibrations for moisture, fat content and acidity gave residual
      predictive deviation (RPD) values of 2.76, 2.37 and 1.60, respectively. Although,
      it is concluded that the on-line NIRS prediction results were acceptable for the
      three parameters measured in intact olive samples in movement, the models
      developed must be improved in order to increase their accuracy before final NIRS
      implementation at mills.

PMID- 23561218
TI  - Polyphasic approach to the identification of Aspergillus section Flavi isolated
      from Brazil nuts.
AB  - The aim of this study was to use a polyphasic approach to identify Aspergillus
      section Flavi isolated from Brazil nuts collected in the Amazon forest:
      investigation of macro- and microscopic morphology, production of extrolites,
      heat-resistance fungi, and sequencing of DNA regions. The following Aspergillus
      section Flavi species were identified: Aspergillus flavus (75.5%), Aspergillus
      nomius (22.3%), and Aspergillus parasiticus (2.2%). All A. nomius and A.
      parasiticus isolates produced aflatoxins B and G, but not cyclopiazonic acid
      (CPA). A. flavus isolates were more diversified and a high frequency of
      mycotoxigenic strains was observed. The polyphasic approach permitted the
      reliable identification of section Flavi species. The rate of mycotoxigenic
      strains was high (92.7%) and mainly included A. flavus strains producing elevated
      levels of aflatoxins and CPA. These results highlight the possibility of co
      occurrence of both toxins, increasing their potential toxic effect in this
      commodity.

PMID- 23561219
TI  - Phospholipids in rice: significance in grain quality and health benefits: a
      review.
AB  - Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are
      only a minor nutrient compared to starch and protein, they may have both
      nutritional and functional significance. We have systemically reviewed the
      literature on the class, distribution and variation of PLs in rice, their
      relation to rice end-use quality and human health, as well as available methods
      for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine
      (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice.
      The deterioration of PC in rice bran during storage was considered as a trigger
      for the degradation of rice lipids with associated rancid flavour in paddy and
      brown rice. The lyso forms in rice endosperm represent the major starch lipid,
      and may form inclusion complexes with amylose, affecting the physicochemical
      properties and digestibility of starch, and hence its cooking and eating quality.
      Dietary PLs have a positive impact on several human diseases and reduce the side
      effects of some drugs. As rice has long been consumed as a staple food in many
      Asian countries, rice PLs may have significant health benefits for those
      populations. Rice PLs may be influenced both by genetic (G) and environmental (E)
      factors, and resolving G*E interactions may allow future exploitation of PL
      composition and content, thus boosting rice eating quality and health benefits
      for consumers. We have identified and summarised the different methods used for
      rice PL analysis, and discussed the consequences of variation in reported PL
      values due to inconsistencies between methods. This review enhances the
      understanding of the nature and importance of PLs in rice and outlines potential
      approaches for manipulating PLs to improve the quality of rice grain and other
      cereals.

PMID- 23561220
TI  - On the origin of sharp peaks in the X-ray diffraction patterns of xanthan
      powders.
AB  - A series of xanthans containing different levels of the charged group pyruvate
      has been examined. The X-ray diffraction patterns of the powders of these
      materials had different levels of a sharp pattern superimposed on an amorphous
      background. As the moisture content increased so the intensity of the sharp
      pattern increased up to a level between 20% and 40% moisture content where the
      sharp pattern disappeared. X-ray diffraction pattern identification software and
      an inorganic X-ray diffraction database showed the origin of the sharp peaks to
      be due to sodium sulphate polymorphs. The behaviour of the xanthans was thought
      to be due to the differences in charge on the molecule; however, the increase in
      the crystalline component observed with increased amounts of water was
      unexpected. The possibility of the drying of samples was considered but the
      interplay between ions, the charged polymer and the water present was considered
      necessary to more closely describe the results.

PMID- 23561221
TI  - Flavour profiles of three novel acidic varieties of muskmelon (Cucumis melo L.).
AB  - Novel acidic varieties of muskmelon (Cucumis melo L.) are emerging onto the UK
      market. These melons contain almost twice the amount of citric acid compared to
      standard melons and are described as 'zesty and fresh'. This study compared the
      flavour components of three acidic varieties with a standard Galia-type melon.
      The volatile and semivolatile compounds were extracted, using dynamic headspace
      extraction (DHE) or solid-phase microextraction (SPME) and solid phase extraction
      (SPE), respectively, followed by gas chromatography-mass spectrometry (GC-MS) and
      gas chromatography-olfactometry (GC-O). More than 50 volatile and 50 semivolatile
      compounds were identified in the headspace and the SPE extracts, respectively. GC
      O revealed 15 odour-active components in the headspace, with esters being
      consistently higher in the acidic variety. This study showed quantitative and
      qualitative differences among all four varieties and key differences between
      acidic varieties and standard melons.

PMID- 23561222
TI  - Separation and purification of the antioxidant compounds, caffeic acid phenethyl
      ester and caffeic acid from mushrooms by molecularly imprinted polymer.
AB  - Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA), two naturally
      occurring phenolic antioxidants, have been reported to have a diversity of
      biological activities. In this investigation, a novel approach to separate and
      enrich CAPE and CA from 25 species of mushrooms using molecularly imprinted
      polymers (MIPs) as the sorbent material is reported. The MIPs were synthesized
      using CAPE as the template, and its adsorption behavior was investigated in
      detail. In comparison with C18-solid phase extraction (SPE), MIP-SPE displayed
      high selectivity and good affinity for CAPE and CA. The antioxidant potential of
      the mushroom extracts, before and after preconcentration using MIPs, was assayed
      by inhibition of erythrocyte hemolysis and lipid peroxidation. Application of
      MIPs with a high affinity toward CAPE and CA provides a novel method for
      obtaining active compounds from natural products.

PMID- 23561223
TI  - Impact of pectin type on the storage stability of black currant (Ribes nigrum L.)
      anthocyanins in pectic model solutions.
AB  - The effects of different pectins on the stabilisation of black currant
      anthocyanins in viscous model solutions at pH 3.0 were investigated. For this
      purpose, low esterified amidated (AM), low (LM) and high (HM) methoxylated citrus
      and apple pectins and a sugar beet pectin were added to a purified anthocyanin
      extract (ACN-E) and to an extract containing anthocyanins and non-anthocyanin
      phenolics (PP-E). Model systems were stored at 20+/-0.5 degrees C in the dark.
      Anthocyanin contents were monitored by HPLC analysis over a period of 18 weeks,
      and half-life and destruction values were calculated. In all pectic model
      solutions anthocyanin stability was significantly improved compared to stability
      of the extracts without added pectins (blank). Best stabilisation was obtained
      with AM pectin, followed by LM and HM pectins. In model systems containing citrus
      pectins, anthocyanin stabilisation was better compared to that of apple pectins
      having similar degrees of esterification and amidation, respectively. This was
      primarily due to the strong interaction of delphinidin glycosides with the citrus
      pectins, whereas stabilisation of cyanidin derivatives was less important. Sugar
      beet pectin improved anthocyanin stability only to a limited extent. In the
      presence of non-anthocyanin phenolics (PP-E) the impact of the pectin source was
      even more pronounced than the effect of the pectin type. Addition of citrate to
      pectic systems accelerated anthocyanin decay. Stabilising effects of pectins were
      hardly noticeable when evaluating total phenolic content (TPC, Folin-Ciocalteu)
      and antioxidant capacity during storage. Highest TPC, TEAC- and FRAP values were
      observed in systems containing citrus pectin, which was in contrast to sugar beet
      pectin, where values fell below those of the blank after storage.

PMID- 23561224
TI  - Morphological characteristics of the human skin over posterior aspect of heel in
      the context of pressure ulcer development.
AB  - The posterior aspect of heel is known as a particularly vulnerable site for
      pressure ulcer development, however, it is not well understood why this is so.
      This study was undertaken to identify the morphological characteristics of the
      skin over posterior aspect of heel in the context of pressure ulcer development.
      Human skin tissues were obtained from four different sites of the body of 4 aged
      subjects postmortem: posterior aspect of heel, plantar aspect of heel, sacrum and
      centre of gluteus maximus. The skin samples were processed for the examination
      using light microscopy and scanning electron microscopy. The posterior aspect of
      heel was characterized by a thicker epidermis, denser distribution and larger
      diameter of capillaries in the papillary layer, 3-dimensional architecture of
      collagen fibre meshwork in the reticular layer and elliptic adipose tissues
      situated perpendicularly to the skin surface being surrounded by thick collagen
      and elastic fibre septa compared to the sacrum. Given our observations in the
      papillary layer of the posterior aspect of heel, we assume that the tissue of
      this area may be less tolerant to ischaemia since the tissue has high metabolic
      demand to provide oxygen and nutrients to the epidermis which protects underlying
      tissue from external force. In addition, elliptic configuration of adipose
      tissues in the posterior aspect of heel situated perpendicularly to the skin
      surface may result in deep lesion if the forces applied exceed the tolerable
      level since the forces will be concentrated within the elliptic compartments.

PMID- 23561225
TI  - CT colonography for diagnosis of symptomatic colorectal cancer: the SIGGAR trials
      and their implication for service delivery.

PMID- 23561226
TI  - Pitfalls in MR morphology of the sterno-costo-clavicular region using whole-body
      MRI.
AB  - AIM: To analyse the imaging findings at the sterno-costo-clavicular (SCC) joint
      region using whole-body (WB) magnetic resonance imaging (MRI) in healthy
      individuals to minimize misinterpretation as changes due to spondyloarthritis
      (SpA). MATERIALS AND METHODS: As part of a cross-sectional study of 122 SpA
      patients, 75 healthy individuals (42/33 males/females; median age 30.3 years;
      range 17.7-63.8 years) were scanned using sagittal and coronal WB short tau
      inversion recovery (STIR) and T1-weighted MRI sequences. The SCC region was
      analysed independently by seven readers for bone marrow oedema (BMO), erosions,
      subchondral fat signal intensity (FSI), and joint fluid accumulation. RESULTS:
      SCC changes simulating inflammation were reported by four or more of the seven
      readers in 15 (20%) healthy individuals (12 male/three female; median age 32.1
      years; range 20.2-48 years). Thirteen individuals (17%) had changes at the
      manubriosternal joint (MSJ); five had BMO, one BMO + erosion, four erosion, two
      erosion + FSI, and one FSI only. Changes at the sternoclavicular joint occurred
      in three individuals (4%) encompassing erosion, erosion + FSI + BMO, and joint
      fluid accumulation, respectively. One patient had both MSJ and sternoclavicular
      joint changes. CONCLUSIONS: Findings mimicking inflammatory changes occurred in
      healthy individuals, particularly in the MSJ. Awareness of this is important in
      recognition of SCC inflammation in SpA.

PMID- 23561227
TI  - Suicide risk assessment received prior to suicide death by Veterans Health
      Administration patients with a history of depression.
AB  - OBJECTIVE: To examine the quality of suicide risk assessment provided to veterans
      with a history of depression who died by suicide between 1999 and 2004. METHOD:
      We conducted a case-control study of suicide risk assessment information recorded
      in 488 medical charts of veterans previously diagnosed with major depression,
      depression not otherwise specified, dysthymia, or other, less common ICD-9-CM
      depression codes. Patients dying by suicide from April 1999 through September
      2004 or comparison patients (n = 244 pairs) were matched for age, sex, entry
      year, and region. RESULTS: Seventy-four percent of patients with a history of
      depression received a documented assessment of suicidal ideation within the past
      year, and 59% received more than 1 assessment. However, 70% of those who died of
      suicide did not have a documented assessment for suicidal ideation at their final
      Veterans Health Administration (VHA) visit, even if that visit occurred within 0
      through 7 days prior to suicide death. Most patients dying by suicide denied
      suicidal ideation when assessed (85%; 95% CI, 75%-92%), even just 0 through 7
      days prior to suicide death (73%; 95% CI, 39%-94%). Suicidal ideation was
      assessed more frequently during outpatient final visits with mental health
      providers (60%) than during outpatient final visits with primary care (13%) or
      other non-mental health providers (10%, P < .0001). CONCLUSIONS: Most VHA
      patients with a history of depression received some suicide risk assessment
      within the past year, but suicide risk assessments were infrequently administered
      at the final visit of patients who eventually died by suicide. Among patients who
      had assessments, denial of suicidal ideation appeared to be of limited value.
      Practice changes are needed to improve suicide risk assessment among patients
      with histories of depression, including the development of assessment and
      prevention strategies that are less dependent on the presence or disclosure of
      suicidal ideation at scheduled medical visits.

PMID- 23561228
TI  - Five-year course of obsessive-compulsive disorder: predictors of remission and
      relapse.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous and disabling
      condition; however, no studies have examined symptom categories or subtypes as
      predictors of long-term clinical course in adults with primary OCD. METHOD: A
      total of 213 adults with DSM-IV OCD were recruited from several mental health
      treatment sites between July 2001 and February 2006 as part of the Brown
      Longitudinal Obsessive Compulsive Study, a prospective, naturalistic study of
      treatment-seeking adults with primary OCD. OCD symptoms were assessed annually
      over the 5-year follow-up period using the Longitudinal Interval Follow-Up
      Evaluation. RESULTS: Thirty-nine percent of participants experienced either a
      partial (22.1%) or a full (16.9%) remission. Two OCD symptom dimensions impacted
      remission. Participants with primary obsessions regarding overresponsibility for
      harm were nearly twice as likely to experience a remission (P < .05), whereas
      only 2 of 21 participants (9.5%) with primary hoarding achieved remission. Other
      predictors of increased remission were lower OCD severity (P < .0001) and shorter
      duration of illness (P < .0001). Fifty-nine percent of participants who remitted
      subsequently relapsed. Participants with obsessive-compulsive personality
      disorder were more than twice as likely to relapse (P < .005). Participants were
      also particularly vulnerable to relapse if they experienced partial remission
      versus full remission (70% vs 45%; P < .05). CONCLUSIONS: The contributions of
      OCD symptom categories and comorbid obsessive-compulsive personality disorder are
      critically important to advancing our understanding of the prognosis and
      ultimately the successful treatment of OCD. Longer duration of illness was also
      found to be a significant predictor of course, highlighting the critical
      importance of early detection and treatment of OCD. Furthermore, having full
      remission as a treatment target is an important consideration for the prevention
      of relapse in this disorder.

PMID- 23561229
TI  - Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg
      in major depressive disorder: a phase 3, randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: This phase 3, randomized, double-blind, placebo-controlled study
      evaluated the efficacy and tolerability of fixed-dose levomilnacipran sustained
      release (SR) compared with placebo in patients with major depressive disorder
      (MDD); the study was conducted from September 2009-May 2011. METHOD: Outpatients
      met DSM-IV-TR criteria for MDD with an ongoing major depressive episode >= 8
      weeks' duration. After a 1-week placebo lead-in, patients were randomly assigned
      to receive placebo (n = 179) or levomilnacipran SR 40 mg (n = 181), 80 mg (n =
      181), or 120 mg (n = 183) once daily for 8 weeks of double-blind treatment,
      followed by a 2-week double-blind down-taper. The primary efficacy parameter was
      change from baseline on the clinician-rated Montgomery-Asberg Depression Rating
      Scale (MADRS) total score. The prespecified secondary efficacy parameter was
      change from baseline in Sheehan Disability Scale (SDS) total score. Additional
      efficacy measures included the 17-item Hamilton Depression Rating Scale
      (HDRS(17)) and Clinical Global Impressions-Severity of Illness (CGI-S) and 
      Improvement (CGI-I). Safety and tolerability were also evaluated. RESULTS: The
      least squares mean difference (LSMD) for change from baseline in MADRS total
      score was significantly superior to placebo for all dose groups: -3.23 (P =
      .0186), -3.99 (P = .0038), and -4.86 (P = .0005) for levomilnacipran SR 40, 80,
      and 120 mg, respectively. The LSMD was significantly different for
      levomilnacipran SR 80 mg and 120 mg versus placebo on the SDS (-2.51 and -2.57,
      respectively, P < .05 for both doses), HDRS(17) (-2.09 and -2.34, respectively, P
      < .05 for both doses), CGI-S (-0.43 [P < .01] and -0.35 [P < .05], respectively),
      and CGI-I (-0.34 and -0.32, respectively, P < .05 for both doses) assessments.
      The most common treatment-emergent adverse events (>= 10% of any treatment group)
      were headache, nausea, constipation, dry mouth, increased heart rate, and
      hyperhidrosis. CONCLUSIONS: Levomilnacipran SR demonstrated significant
      improvement in depressive symptoms and functioning relative to placebo. In this
      study, levomilnacipran SR was generally well tolerated. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00969709.

PMID- 23561230
TI  - Extreme attributions predict the course of bipolar depression: results from the
      STEP-BD randomized controlled trial of psychosocial treatment.
AB  - OBJECTIVE: Little is known about predictors of recovery from bipolar depression
      or moderators of treatment response. In the present study, we investigated
      attributional style (a cognitive pattern of explaining the causes of life events)
      as a predictor of recovery from episodes of bipolar depression and as a moderator
      of response to psychotherapy for bipolar depression. METHOD: 106 depressed
      outpatients with DSM-IV bipolar I or II disorder who were enrolled in the
      Systematic Treatment Enhancement Program for Bipolar Disorder were randomly
      assigned to intensive psychotherapy for depression (n = 62) or to collaborative
      care (n = 44), a minimal psychoeducational intervention. The primary outcome was
      recovery status at each study visit as measured by the Clinical Monitoring Form.
      Attributional style was measured at baseline using the Attributional Style
      Questionnaire. Data were collected between 1998 and 2005. RESULTS: All analyses
      were by intention to treat. Extreme attributions predicted a lower likelihood of
      recovery (P < .01; OR = 0.93; 95% CI, 0.88-0.98) and longer time until recovery
      (P < .01; OR = 0.96; 95% CI, 0.93-0.99), independent of the effects of initial
      depression severity. Among individuals with more pessimistic attributional
      styles, higher initial depression severity predicted a lower likelihood of
      recovery (P = .01; OR = 0.64; 95% CI, 0.45-0.91) and longer time until recovery
      (P < .001; OR = 0.76; 95% CI, 0.66-0.88). There was no difference in recovery
      rates between intensive psychotherapy and collaborative care (OR = 0.90; 95% CI,
      0.40-2.01) in the full sample. CONCLUSIONS: These results suggest that extreme,
      rigid attributions may be associated with a more severe course of depression and
      that evaluating attributional style may help clinicians to identify patients who
      are at risk for experiencing a more severe course of depression. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT00012558.

PMID- 23561232
TI  - Teaching the teacher: a report from the third annual American Society of Clinical
      Psychopharmacology teaching session.

PMID- 23561231
TI  - Sexual satisfaction and quality of life in major depressive disorder before and
      after treatment with citalopram in the STAR*D study.
AB  - OBJECTIVE: Major depressive disorder (MDD) patients often experience impaired
      sexual satisfaction (ISS) and poor quality of life (QOL). Selective serotonin
      reuptake inhibitors (SSRIs), the first-line treatment for MDD, can cause sexual
      dysfunction, potentially worsening ISS and QOL. This study examined the impact of
      MDD and the SSRI citalopram on sexual satisfaction and QOL in level 1 of the
      Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (July 2001
      September 2006). METHOD: A retrospective analysis was conducted of the change in
      sexual satisfaction, as measured by item 9 of the Quality of Life Enjoyment and
      Satisfaction Questionnaire, the primary outcome measure, in 2,280 patients with
      DSM-IV-TR-defined MDD who were treated with citalopram for 12 weeks. The Quick
      Inventory of Depressive Symptomatology-Self Report was used to evaluate the
      impact of depression ratings on impaired sexual satisfaction and on QOL. RESULTS:
      Impaired sexual satisfaction was present in 64.3% of MDD patients at
      pretreatment, but that percentage declined to 47.1% at posttreatment with
      citalopram (P < .0001). Those who achieved remission had less ISS and better QOL.
      The prevalence of ISS in remitters was 21.2% versus 61.3% in nonremitters (P <
      10(-8)). The mean +/- standard deviation score for remitters increased from 2.32
      +/- 1.16 to 3.44 +/- 1.23 (P < 10(-8); Cohen d = 0.81 [large effect size]),
      whereas in nonremitters it increased only from 1.99 +/- 1.08 to 2.19 +/- 1.19 (P
      < 10(-8); Cohen d = 0.16). The difference between remitters and nonremitters was
      highly significant (P < 10(-8)). Regression analyses at pretreatment and
      posttreatment demonstrated significant associations between depressive symptoms
      and ISS (P < .0001) and between ISS and lower QOL (P < .0001) as well as an
      association between citalopram and increased probability of ISS and a poorer QOL
      in patients who continue to have moderate-to-severe depression. CONCLUSIONS: A
      majority of MDD patients have impaired sexual satisfaction, a symptom associated
      with poor QOL. Despite the sexual side effects of the SSR citalopram, treating
      depression to full remission was associated with improvements in sexual
      satisfaction and QOL. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00021528.

PMID- 23561233
TI  - Generalizability of clinical trial results for bipolar disorder to community
      samples: findings from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - BACKGROUND: Research on the generalizability of clinical trial results for
      bipolar disorder is limited. The present post hoc study sought to quantify the
      generalizability of clinical trial results in individuals with DSM-IV bipolar
      disorder to a large representative community sample. METHOD: Data were derived
      from the 2001-2002 National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC), a large, nationally representative sample of 43,093 adults
      from the United States population. We applied a standard set of eligibility
      criteria representative of clinical trials to all adults with DSM-IV bipolar
      depression (n = 785) or mania (n = 724) in the past 12 months and then to a
      subsample of participants seeking treatment for bipolar depression (n = 276). Our
      aim was to determine the proportion of participants with bipolar depression or
      acute mania who would have been excluded from a clinical trial by typical
      eligibility criteria. RESULTS: We found that more than 5 of 10 participants with
      bipolar depression (58.17%) or mania (55.75%) would have been excluded by at
      least 1 eligibility criterion. In the subgroup of participants with bipolar
      depression who sought treatment, the exclusion rate by at least 1 criterion was
      higher (63.87%). Having a significant risk of suicide was the criterion excluding
      the highest percentage of participants in the bipolar depression samples, while
      having a current DSM-IV diagnosis of alcohol abuse or dependence was the one
      leading to the greatest exclusion rate in clinical trials for participants with
      acute mania. Exclusion rates were higher for participants with bipolar I
      depression compared with those with bipolar II depression. CONCLUSIONS:
      Traditional clinical trials tend to exclude a majority of individuals with
      bipolar disorder. Clinical trials should carefully consider the impact of
      eligibility criteria on the generalizability of their results and explain the
      rationale for their use. Future trials should weigh the trade-offs between
      internal validity and the representativeness of the study.

PMID- 23561234
TI  - A prevalence study of urinary tract infections in acute relapse of schizophrenia.
AB  - OBJECTIVE: Schizophrenia is associated with immune abnormalities and increased
      mortality from infectious diseases. The aim of this study was to examine whether
      acute relapse of schizophrenia was associated with urinary tract infection (UTI),
      in comparison with controls, after controlling for potential confounding factors.
      METHOD: In a prevalence study conducted from January 2010 to April 2012 at
      Georgia Health Sciences University Medical Center, Augusta, we recruited 136
      adult subjects (mean age = 42.8 years): 57 inpatients with an acute relapse of
      DSM-IV schizophrenia, 40 stable outpatients with DSM-IV schizophrenia, and 39
      healthy controls from the community. Urinary tract infection was defined as
      having positive leukocyte esterase and/or positive nitrites on urinalysis and
      having >= 5 leukocytes per high-powered field (implies 5-10 or more) on urine
      microscopy. Determination of UTI status was made for each subject, and analyses
      were performed to examine the association between UTI and acute relapse of
      schizophrenia. RESULTS: 35% of acutely relapsed subjects, versus 5% of stable
      outpatients and 3% of controls, had a UTI (P < .001). Only 40% of subjects in the
      acute relapse group classified as having a UTI were treated with antibiotics
      during hospitalization. After analyses were controlled for gender and smoking
      status, subjects in the acute relapse group were almost 29 times more likely to
      have a UTI than controls (odds ratio = 28.97; 95% CI, 3.44-243.85; P = .002).
      There was no statistically significant association with UTI among the stable
      outpatients versus controls. CONCLUSIONS: Our finding of an association between
      an increased prevalence of UTI and acute psychotic relapse warrants replication
      in other samples. The mechanism of this association remains unclear. The results
      also highlight the potential importance of monitoring for comorbid UTI in acutely
      relapsed patients with schizophrenia.

PMID- 23561235
TI  - Reconsidering chronic hyponatremia in psychosis.

PMID- 23561236
TI  - Subjective assessments of threats and their association to posttraumatic stress
      disorder symptoms: the case of the 2011 Japan earthquake and nuclear disaster.

PMID- 23561237
TI  - Understanding the physiology of schizophrenia.
AB  - The physiology of schizophrenia includes complex genetic and environmental
      interactions. Current treatment largely focuses on positive symptoms, but many
      patients with schizophrenia present with additional symptoms and conditions that
      hinder their social and occupational functioning. The study of the physiology of
      this disorder has expanded beyond dopamine dysfunction to include the glutamate,
      serotonin, and nicotinic/acetylcholine systems, as well as physiologic
      abnormalities such as diabetes and inflammation. Clinicians who understand these
      additional problem areas can incorporate them into their assessment and treatment
      plans for patients with schizophrenia.

PMID- 23561239
TI  - Antidepressant action of atypical antipsychotics: focus on ziprasidone
      monotherapy, with a few twists in the tale.

PMID- 23561240
TI  - Posttraumatic stress disorder in adult attention-deficit/hyperactivity disorder:
      clinical features and familial transmission.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is characterized by
      clinically significant functional impairment due to symptoms of inattention
      and/or hyperactivity and impulsivity. Previous research suggests a link, in child
      samples, between ADHD and posttraumatic stress disorder (PTSD), which is
      characterized by (1) chronically reexperiencing a traumatic event, (2)
      hyperarousal, and (3) avoiding stimuli associated with the trauma while
      exhibiting numbed responsiveness. This study sought to address the link between
      ADHD and PTSD in adults by providing a comprehensive comparison of ADHD patients
      with and without PTSD across multiple variables including demographics, patterns
      of psychiatric comorbidities, functional impairments, quality of life, social
      adjustment, and familial transmission. METHOD: Participants in our controlled
      family study conducted between 1998 and 2003 were 190 adults with DSM-IV ADHD who
      were attending an outpatient mental health clinic in Boston, Massachusetts; 16
      adults with DSM-IV ADHD who were recruited by advertisement from the greater
      Boston area; and 123 adult controls without ADHD who were recruited by
      advertisement from the greater Boston area. All available first-degree relatives
      also participated. Subjects completed a large battery of self-report measures
      (the Quality of Life Enjoyment and Satisfaction Questionnaire, items from the
      Current Behavior Scale, the Social Adjustment Scale Self-Report, and the Four
      Factor Index of Social Status) designed to assess various psychiatric and
      functional parameters. Diagnoses were made using data obtained from structured
      psychiatric interviews (Structured Clinical Interview for DSM-IV Axis I
      Disorders, Clinician Version, and the Schedule for Affective Disorders and
      Schizophrenia for School-Aged Children-Epidemiologic Version). RESULTS: The
      lifetime prevalence of PTSD was significantly higher among adults with ADHD
      compared with controls (10.0% vs 1.6%; P = .004). Participants with ADHD and
      those with ADHD + PTSD did not differ in core symptoms of ADHD nor in age at
      onset, but those with ADHD + PTSD had higher rates of psychiatric comorbidity
      than those with ADHD only (including higher lifetime rates of major depressive
      disorder, oppositional defiant disorder, social phobia, agoraphobia, and
      generalized anxiety disorder) and worse quality of life ratings for all domains.
      Familial risk analysis revealed that relatives of ADHD probands without PTSD had
      elevated rates of both ADHD (51%) and PTSD (12%) that significantly differed from
      rates among relatives of controls (7% [P <= .001] and 0% [P <= .05],
      respectively). A similar pattern of elevated risk for ADHD and PTSD (80% and 40%)
      was observed in relatives of probands with ADHD + PTSD (P <= .001 for both
      conditions). CONCLUSIONS: The comorbidity of PTSD and ADHD in adults leads to
      greater clinical severity in terms of psychiatric comorbidity and psychosocial
      functioning. The familial coaggregation of the 2 disorders suggests that these
      disorders share familial risk factors and that their co-occurrence is not due to
      diagnostic errors.

PMID- 23561242
TI  - Co-occurrence of major depressive episode and posttraumatic stress disorder among
      survivors of war: how is it different from either condition alone?
AB  - OBJECTIVE: Major depressive episode (MDE) and posttraumatic stress disorder
      (PTSD) have been shown to be the most common mental disorders following traumatic
      war experiences and have been found to frequently co-occur. This study, designed
      as a randomized cross-sectional interview survey, aimed to identify whether the
      co-occurence of MDE and PTSD following exposure to war-related experiences is
      associated with different demographics, exposure to previous traumatic events,
      and clinical characteristics than either condition alone. METHOD: After a random
      walk technique was used to randomly select participants, face-to-face interviews
      were conducted among war-affected community samples in 5 Balkan countries (N =
      3,313) in the years 2006 and 2007. The mean age of participants was 42.3 years,
      and all participants had experienced potentially traumatic events during war in
      the countries of the former Yugoslavia. Current prevalence rates of MDE and PTSD
      and suicide risk were assessed using the Mini-International Neuropsychiatric
      Interview. Levels of general psychological distress, posttraumatic stress, and
      quality of life were assessed with self-reports. RESULTS: 30.5% of the sample met
      DSM-IV diagnostic criteria for either MDE or PTSD, and 9.1% had both disorders.
      Participants with concomitant MDE and PTSD reported significantly higher numbers
      of prewar and postwar traumatic events than participants with PTSD only and
      higher numbers of war-related events than those with MDE only (all P values <
      .001). Participants with both MDE and PTSD had significantly higher levels of
      general psychological and posttraumatic stress symptoms, a higher suicide risk,
      and lower levels of quality of life than participants with either condition alone
      (all P values < .001). CONCLUSIONS: Concomitant MDE and PTSD are associated with
      the experience of different traumatic events and are characterized by more
      general psychological distress than either condition alone. The assessment of
      concomitant MDE and PTSD can facilitate better identification of individuals with
      severe psychopathology and poor quality of life. People with co-occurrence of MDE
      and PTSD may require specific health care programs following war.

PMID- 23561241
TI  - Recovery from multiple episodes of bipolar I depression.
AB  - OBJECTIVE: To describe the duration of bipolar I major and minor depressive
      episodes and factors associated with time to recovery. METHOD: As part of the
      National Institute of Mental Health Collaborative Depression Study, 219
      participants with bipolar I disorder based on Research Diagnostic Criteria
      analogs to DSM-IV-TR criteria were recruited at 5 academic medical centers from
      1978 to 1981 and followed for up to 25 years with the Longitudinal Interval
      Follow-Up Evaluation. The probability of recovery over time from depressive
      episodes, the primary outcome measure, was examined with mixed-effects grouped
      time survival models. RESULTS: The median duration of major depressive episodes
      was 14 weeks, and over 70% of participants recovered within 12 months of episode
      onset. The median duration of minor depressive episodes was 8 weeks, and
      approximately 90% of participants recovered within 6 months of onset of the
      episode. Aggregated data demonstrated similar durations of the first 3 major
      depressive episodes. However, for each participant with multiple episodes of
      major depression or minor depression, the duration of each episode was not
      consistent (intraclass correlation coefficient = 0.07 and 0.25 for major and
      minor depression, respectively). The total number of years in episode over follow
      up with major plus minor depression prior to onset of a major depressive episode
      was significantly associated with a decreased probability of recovery from that
      episode; with each additional year, the likelihood of recovery was reduced by 7%
      (hazard ratio = 0.93; 95% CI, 0.89-0.98; P = .002). CONCLUSIONS: Bipolar I major
      depression generally lasts longer than minor depression, and the duration of
      multiple episodes within an individual varies. However, the probability of
      recovery over time from an episode of major depression appears to decline with
      each successive episode.

PMID- 23561243
TI  - [Cerebral calcifications in systemic lupus erythematosus].

PMID- 23561244
TI  - [Chylous ascites].

PMID- 23561246
TI  - The epidemiology of gonorrhoea in London: a Bayesian spatial modelling approach.
AB  - Data obtained from genitourinary medicine clinics through a comprehensive
      surveillance system were used in a Bayesian mixed-effects Poisson regression
      model to explore socio-demographic individual and ecological risk factors for
      gonorrhoea in London, as well as its spatial clustering. The spatial analysis was
      performed at the Middle-layer Super Output Area level (median population size
      7200). A total of 12452 individuals were diagnosed during the 2-year study period
      (2009-2010). The study confirmed the presence of 'core areas' of high incidence,
      and identified 'core' high-risk groups, in particular young adults (16-29 years),
      males, black Caribbeans and more deprived areas. The individual (age, sex,
      ethnicity) and area-level (deprivation, teenage pregnancies, students) model
      covariates accounted for 48% of the variance. Most of the remaining variance was
      explained by the spatial effect, thus capturing other spatially distributed
      factors associated with gonorrhoea, such as local sexual networks. These findings
      will be useful in identifying areas for targeted interventions, such as STI
      testing and health promotion.

PMID- 23561247
TI  - Epidemiology of migraine in the She ethnic minority group in Fujian province,
      China.
AB  - OBJECTIVES: We examined the prevalence and risk factors of migraine among the She
      population. The prevalence of migraine among She Chinese in Fujian province is
      high. METHODS: This study is a cross-sectional survey. Subjects completed a
      questionnaire that collected demographic and clinical data related to migraine.
      Physical examination and clinical laboratory tests were performed. Data were
      analyzed by regression analysis. RESULTS: Of the 5519 subjects enrolled, 2377
      were male (43.1%) and 3142 female (56.9%). Of these, 581 (10.53%) experienced
      migraine annually, including 6.18% of males and 13.82% of females. Highest
      prevalence rate was among those aged 40-49 years (11.28%). The 141 (24.3%)
      subjects who had migraine with aura had higher incidence of family history of
      headache than those without aura (38.5% vs 19.9%, P < 0.0001). CONCLUSION: Female
      gender and insomnia are possible risk factors for migraine in the She population.

PMID- 23561245
TI  - Artemisinin resistance in rodent malaria--mutation in the AP2 adaptor MU-chain
      suggests involvement of endocytosis and membrane protein trafficking.
AB  - BACKGROUND: The control of malaria, caused by Plasmodium falciparum, is hampered
      by the relentless evolution of drug resistance. Because artemisinin derivatives
      are now used in the most effective anti-malarial therapy, resistance to
      artemisinin would be catastrophic. Indeed, studies suggest that artemisinin
      resistance has already appeared in natural infections. Understanding the
      mechanisms of resistance would help to prolong the effective lifetime of these
      drugs. Genetic markers of resistance are therefore required urgently. Previously,
      a mutation in a de-ubiquitinating enzyme was shown to confer artemisinin
      resistance in the rodent malaria parasite Plasmodium chabaudi. METHODS: Here, for
      a mutant P. chabaudi malaria parasite and its immediate progenitor, the in vivo
      artemisinin resistance phenotypes and the mutations arising using Illumina whole
      genome re-sequencing were compared. RESULTS: An increased artemisinin resistance
      phenotype is accompanied by one non-synonymous substitution. The mutated gene
      encodes the MU-chain of the AP2 adaptor complex, a component of the endocytic
      machinery. Homology models indicate that the mutated residue interacts with a
      cargo recognition sequence. In natural infections of the human malaria parasite
      P. falciparum, 12 polymorphisms (nine SNPs and three indels) were identified in
      the orthologous gene. CONCLUSION: An increased artemisinin-resistant phenotype
      occurs along with a mutation in a functional element of the AP2 adaptor protein
      complex. This suggests that endocytosis and trafficking of membrane proteins may
      be involved, generating new insights into possible mechanisms of resistance. The
      genotypes of this adaptor protein can be evaluated for its role in artemisinin
      responses in human infections of P. falciparum.

PMID- 23561248
TI  - The relationship between cognitive impairment and cerebral blood flow changes
      after transient ischaemic attack.
AB  - OBJECTIVE: The associations between cognitive impairment following the initial
      onset of transient ischaemic attack (TIA) and the parameters of altered cerebral
      blood flow and high-sensitivity C-reactive protein (HsCRP) level are unclear.
      METHODS: A total of 97 first-time TIA patients aged 69.94 +/- 4.02 years (38-75
      years; M:F, 50:47) hospitalized between March 2010 and July 2011 were compared to
      100 healthy control patients aged 66.56 +/- 12.15 years (45-80 years; M:F,
      60:40). Cognitive function was quantified by Montreal Cognitive Assessment
      (MoCA). Intracranial blood flow was measured using transcranial Doppler
      ultrasound, and HsCRP levels were assessed using the Spearman correlation
      coefficient. Relationships between both values and MoCA scores were examined.
      RESULTS: Transient ischaemic attack patients exhibited declined cognitive
      function manifested as impaired verbal fluency (97.93%), memory recall (91.75%),
      abstraction (84.53%), and visuospatial/executive abilities (79.38%). To a lesser
      degree, TIA patients also evidenced abnormalities in attention (50.52%), naming
      (20.62%), and orientation (20.62%). Furthermore, MoCA scores significantly
      correlated with high HsCRP levels and low vascular systolic peak velocities
      (P<0.001). Vascular systolic peak velocities were high in nine patients (9.23%)
      and low in 57 patients (58.76%). Thus, cognitive impairment was closely related
      to HsCRP levels and intracranial blood flow velocities. CONCLUSION: Post-TIA
      cognitive impairment may result from atherosclerosis and reduced blood flow to
      the brain. Cognitive impairment, transcranial Doppler-visualized changes, and
      elevated HsCRP levels are important diagnostic indicators of TIA. Markers
      provided by cognitive evaluation of TIA patients following the initial onset of
      TIA may allow clinicians to better predict and prevent adverse vascular events.

PMID- 23561249
TI  - Shared decision making: moving from theorization to applied research and
      hopefully to clinical practice.

PMID- 23561250
TI  - Carbon-ion radiotherapy for marginal lymph node recurrences of cervical cancer
      after definitive radiotherapy: a case report.
AB  - Recurrences of cervical cancer after definitive radiotherapy often occur at
      common iliac or para-aortic lymph nodes as marginal lymph node recurrences.
      Patients with these recurrences have a chance of long-term survival by optimal re
      treatment with radiotherapy. However, the re-irradiation often overlaps the
      initial and the secondary radiotherapy fields and can result in increased normal
      tissue toxicities in the bowels or the stomach. Carbon-ion radiotherapy, a form
      of particle beam radiotherapy using accelerated carbon ions, offers more
      conformal and sharp dose distribution than X-ray radiotherapy. Therefore, this
      approach enables the delivery of high radiation doses to the target while sparing
      its surrounding normal tissues. Marginal lymph node recurrences in common iliac
      lymph nodes after radiotherapy were treated successfully by carbon-ion
      radiotherapy in two patients. These two patients were initially treated with a
      combination of external beam radiotherapy and intracavitary and interstitial
      brachytherapy. However, the diseases recurred in the lymph nodes near the border
      of the initial radiotherapy fields after 22 months and 23 months. Because re
      irradiation with X-ray radiotherapy may deliver high doses to a section of the
      bowels, carbon-ion radiotherapy was selected to treat the lymph node recurrences.
      A total dose of 48 Gy (RBE) in 12 fractions over 3 weeks was given to the lymph
      node recurrences, and the tumors disappeared completely with no severe acute
      toxicities. The two patients showed no evidence of disease for 75 months and 63
      months after the initial radiotherapy and for 50 months and 37 months after the
      carbon-ion radiotherapy, respectively. No severe late adverse effects are
      observed in these patients. The two presented cases suggest that the highly
      conformal dose distribution of carbon-ion radiotherapy may be beneficial in the
      treatment of marginal lymph node recurrences after radiotherapy. In addition, the
      higher biological effect of carbon-ion radiotherapy and its superior dose
      distribution may provide more effective tumor control in treatment for re
      irradiation of the marginal recurrences in radiation resistant tumors other than
      cervical cancer.

PMID- 23561252
TI  - Cluster of diffuse alveolar hemorrhage cases after the 2011 Tohoku Region Pacific
      Coast Earthquake.
AB  - BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a clinical syndrome that
      presents with progressively hemorrhagic bronchoalveolar lavage fluid (BALF) in
      serial samples and generally has a poor prognosis. The South Miyagi Medical
      Center, located on the inland side of southern Miyagi Prefecture, documented an
      increase in the number of patients with DAH after the 2011 Tohoku Region Pacific
      Coast Earthquake. METHODS: We describe the clinical features of post-earthquake
      DAH in comparison to pre-earthquake DAH. We analyzed the data of the DAH patients
      we have been able to follow for at least 6 months since we started performing
      bronchoscopy and bronchoalveolar lavage (BAL) for all patients with interstitial
      lung disease in August 2009 until September 2011, and separated these patients
      into pre- and post-earthquake groups according to the earthquake date of March
      11, 2011. RESULTS: Post-earthquake DAH patients tended to test positive for
      infectious agents and showed higher serum IgE titers, with BALF that exhibited a
      tendency to higher silica concentrations. Post-earthquake DAH generally had a
      better prognosis than pre-earthquake DAH. CONCLUSIONS: In describing the clinical
      features of post-earthquake cases of DAH, this report documents the possibility
      of an infection- and/or dust-induced, partially allergic, and relatively benign
      form of DAH.

PMID- 23561253
TI  - Questionnaire survey on the continuity of home oxygen therapy after a disaster
      with power outages.
AB  - BACKGROUND: After the Great East Japan Earthquake, oxygen-dependent patients in
      areas experiencing power outages could not continue home oxygen therapy (HOT)
      without oxygen cylinders. The purpose of this study was to examine use of oxygen
      cylinders in areas experiencing power outages and the effects of HOT interruption
      on patients' health. METHODS: Questionnaires were mailed to 1106 oxygen-dependent
      patients and HOT-prescribing physicians in Akita, near the disaster-stricken
      area. We investigated patients' actions when unable to use an oxygen concentrator
      and classified the patients based on oxygen cylinder use. Patients who
      experienced an interruption of or reduction in oxygen flow rate by their own
      judgment were assigned to the "interruption" and "reduction" groups,
      respectively; those who maintained their usual flow rate were assigned to the
      "continuation" group. Differences were tested using analysis of variance and the
      chi2 tests. RESULTS: In total, 599 patients responded to the questionnaire.
      Oxygen cylinders were supplied to 574 patients (95.8%) before their oxygen
      cylinders were depleted. Comparison of the continuation (n=356), reduction
      (n=64), and interruption (n=154) groups showed significant differences in family
      structure (p=0.004), underlying disease (p=0.014), oxygen flow rate (p<0.001),
      situation regarding use (p<0.001), knowledge of HOT (p<0.001), and anxiety about
      oxygen supply (p<0.001). There were no differences in changes in physical
      condition. CONCLUSIONS: Most patients could receive oxygen cylinders after the
      disaster. Some patients discontinued their usual oxygen therapy, but their
      overall health status was not affected.

PMID- 23561254
TI  - Impact of a large-scale natural disaster on patients with chronic obstructive
      pulmonary disease: the aftermath of the 2011 Great East Japan Earthquake.
AB  - BACKGROUND: A large-scale natural disaster may exacerbate chronic respiratory
      diseases, such as chronic obstructive pulmonary disease (COPD). The aftermath of
      a natural disaster can include poor access to medication, medical equipment, and
      medical supplies. Little is known about the impact on patients with COPD.
      METHODS: A retrospective cohort study was conducted at a regional medical center
      in Ishinomaki, the area affected most severely by the Great East Japan Earthquake
      in 2011. The study was performed 6 months after the disaster. The
      characteristics, clinical courses, and outcomes of COPD patients hospitalized
      after emergency visits during the study period were investigated and compared.
      RESULTS: One hundred patients (112 episodes) were identified. Within a few days
      after the disaster, patients undergoing oxygen therapy at home came to the
      hospital to receive oxygen. In the subacute phase (from the third to the fifth
      week), the number of hospitalizations due to COPD exacerbations was significantly
      increased compared to the numbers observed before the earthquake (p<0.05). On
      admission, COPD patients reported significantly reduced participation in the
      activities of daily living (ADLs) after as compared to before the disaster. The
      incidence of cases of exacerbated COPD normalized 6 weeks after the earthquake.
      CONCLUSIONS: The large-scale natural disaster that hit Japan in 2011 had a
      serious negative impact on the clinical outcomes of COPD patients in the disaster
      affected area.

PMID- 23561255
TI  - Chest injuries and the 2011 Great East Japan Earthquake.
AB  - BACKGROUND: Chest injuries caused during a major earthquake remain unclear. We
      have described profiles of patients with chest injuries who were diagnosed and
      treated at the area that was most affected by the Great East Japan Earthquake in
      2011. METHODS: We retrospectively reviewed medical records of 3938 patients who
      were transferred to the Japanese Red Cross Ishinomaki Hospital during the first
      week after the earthquake (March 11-17). In total, 77 patients were declared dead
      on arrival at the hospital. Of the remaining 3861 patients, 42 (1.1%) sustained
      chest injuries. Diagnosis of the chest injury was based on results of physical
      examination, chest radiography, and computed tomography. RESULTS: Chest injury
      was diagnosed in 42 patients, including 22 men and 20 women (age range, 21-99
      years). The most common cause of injury was tsunami (n=21), followed by falls
      (n=9), and traffic accidents (n=1), although this information was missing in 11
      cases. The most common type of chest injury was superficial trauma such as
      laceration and contusion (n=37). Only 5 patients had rib fractures with
      intrathoracic damages such as pneumothorax (n=3), hemothorax (n=1), and
      aspiration (n=1). CONCLUSIONS: The number of patients with chest injury was
      surprisingly small. Most patients did not require hospitalization. The small
      number of survivors with serious chest injuries can most likely be explained by
      the tsunami caused by the earthquake.

PMID- 23561256
TI  - Phase II study of irinotecan as a third- or fourth-line treatment for advanced
      non-small cell lung cancer: NJLCG0703.
AB  - BACKGROUND: We aimed to evaluate the efficacy and safety of irinotecan
      monotherapy as a third- or fourth-line treatment for advanced non-small cell lung
      cancer (NSCLC) patients. METHODS: Patients with advanced NSCLC refractory to 2 or
      more previous regimens were treated with 80 mg/m2 irinotecan on days 1, 8, and
      15, every 4 weeks. The primary endpoint was the overall response rate (ORR),
      whereas secondary endpoints included progression-free survival (PFS), overall
      survival (OS), and toxicity profiles. RESULTS: From December 2007 to April 2009,
      32 patients (median age, 60 years) were enrolled. Most of the patients (75.0%)
      were male, and 18.8% had a performance status of 2. Six partial responses to
      irinotecan monotherapy were observed (ORR, 18.8%: 95% confidence interval, 5.3%
      32.3%). The disease control rate (DCR) was 78.1%, median PFS was 4.0 months, and
      median survival time (MST) was 10.4 months. Grade 3-4 neutropenia was observed in
      22% of patients, but other toxic effects were moderate. No cases of grade 3-4
      diarrhea or treatment-related death were noted. Of the 15 patients for whom
      progressive disease represented the best response to previous treatment regimens,
      2 exhibited a partial response and 9 showed stable disease after irinotecan
      monotherapy, with a DCR of 73.3%, median PFS of 4.4 months, and MST of 8.2
      months. CONCLUSIONS: Irinotecan monotherapy is effective for advanced NSCLC
      patients who have previously failed 2 or more treatment regimens.

PMID- 23561257
TI  - Re-expansion pulmonary edema: evaluation of risk factors in 173 episodes of
      spontaneous pneumothorax.
AB  - BACKGROUND: The precise incidence and clinical features of re-expansion pulmonary
      edema (RPE) are unclear, and they vary among reports. In this study, we assessed
      the incidence, risk factors, and outcomes of patients with RPE over a 3-yr period
      in a general hospital, with the goal of proposing a primary intervention for
      pneumothorax. METHODS: We retrospectively reviewed records of inpatients with
      spontaneous pneumothorax treated by tube thoracostomy between October 2007 and
      December 2010. RESULTS: A total of 173 episodes of spontaneous pneumothorax
      occurred in 156 patients. The incidence of RPE was 27/173 (15.6%). Symptom
      duration and pneumothorax size were significant risk factors for RPE, and the
      occurrence of RPE was independent of primary treatment of spontaneous
      pneumothorax. Among the patients with RPE, 18 (67%) were symptomatic. Five
      patients (18.5%) were treated with temporary oxygen, however, 21 patients (78%)
      did not need any treatment. All patients survived and none required mechanical
      ventilation. The occurrence of RPE did not influence the clinical outcome.
      CONCLUSIONS: The risk of developing RPE increases with an increased duration or
      size of pneumothorax. Our results suggest that the methods of primary
      intervention, including prompt suction, do not affect the onset of RPE. Close
      observation is always required regardless of the intervention because of the
      potentially fatal complications.

PMID- 23561258
TI  - Case of adult T-cell leukemia/lymphoma with rapid progression of pulmonary areas
      of ground-glass attenuation and multiple nodules.
AB  - We report a case of adult T-cell leukemia/lymphoma (ATL) with rapidly progressive
      pulmonary areas of ground-glass attenuation (GGA) and nodules resulting from
      acute transformation of chronic ATL. A 48-year-old Japanese man was admitted for
      progressive dyspnea. Chest computed tomography showed rapidly progressive
      bilateral pulmonary areas of GGA and nodules. Flow cytometry of bronchoalveolar
      lavage fluid and immunohistochemical examination of lung biopsy specimens
      revealed invasion of ATL cells. Systemic chemotherapy improved the pulmonary
      findings. Rapidly expanding areas of GGA and nodules are a rare manifestation of
      pulmonary invasion of ATL that clinicians should nevertheless keep in mind.

PMID- 23561259
TI  - Crizotinib administered via nasogastric and percutaneous endoscopic gastrostomy
      tubes for the successful treatment of ALK-rearranged lung cancer in a patient
      with poor performance status.
AB  - Crizotinib-an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-is
      effective in non-small-cell lung cancers (NSCLCs) that express ALK. Here, we
      report a patient with ALK-positive lung adenocarcinoma who was administered
      crizotinib via nasogastric and percutaneous endoscopic gastrostomy (PEG) tubes,
      with positive results. This case indicates that patients with ALK-positive NSCLC
      may successfully be treated with crizotinib via nasogastric or PEG tubes. This
      approach can even be used as a salvage treatment in patients with poor prognoses.

PMID- 23561260
TI  - Occurrence and genetic diversity of Arcobacter spp. in a spinach-processing plant
      and evaluation of two Arcobacter-specific quantitative PCR assays.
AB  - Some species of the genus Arcobacter are considered to be emerging food
      pathogens. With respect to recent vegetable-borne outbreaks, the aim of this work
      was to investigate the occurrence and diversity of Arcobacter within the
      production chain of a spinach-processing plant by a combination of cultivation
      and molecular methods. Samples including spinach, water, and surface biofilm were
      taken over a period of three years from the entire processing line. Ten 16S rRNA
      (rrs) gene clone libraries were constructed and analysed using amplified rRNA
      gene restriction analysis (ARDRA). Approximately 1200 clones were studied that
      resulted in 44 operational taxonomic units (OTUs). Sequences with high
      similarities to Arcobacter cryaerophilus (13% of clones, 3 OTUs), A. ellisii (4%,
      6 OTUs), A. suis (15%, 3 OTUs), and the type strain of A. nitrofigilis (1%, 7
      OTUs) were identified. This represents the first report of the detection of the
      recently described species A. ellisii, A. suis and, in addition, A. venerupis
      from alternative habitats. A total of 67% of the clones (22 OTUs) could not be
      assigned to a genus, which indicated the presence of uncharacterised Arcobacter
      species. For the cultivation-independent detection of Arcobacter, two genus
      specific quantitative PCR (qPCR) assays were developed and tested on 15
      Arcobacter species. When these assays were applied to samples from the spinach
      processing plant, they showed positive results for up to 35% of the samples and
      supported the conclusion that there is a considerable risk for the transfer of
      pathogenic Arcobacter species on vegetables, which was also verified by a
      cultivation approach.

PMID- 23561261
TI  - Inferior alveolar nerve lateralization: a dual technique.

PMID- 23561262
TI  - Carcinoma ex pleomorphic adenoma in a Brazilian population: clinico-pathological
      analysis of 38 cases.
AB  - Carcinoma ex pleomorphic adenoma (CXPA) is a rare tumour, with different
      prevalence rates reported among studies. Epidemiological studies of large series
      of CXPAs in developing countries are scarce. The aim of the present study was to
      describe Brazilian patients with CXPA; this was a retrospective study of 38
      patients. Demographic and clinico-pathological features were evaluated. No
      preferential gender was found, and the mean age at diagnosis was 57.6 years. The
      most commonly involved site was the parotid, followed by the submandibular and
      the minor salivary glands. A prevalence of clinical stages III and IV was
      observed at diagnosis. The most common histological subtypes were salivary duct
      carcinoma, adenocarcinoma not otherwise specified, myoepithelial carcinoma, and
      epithelial-myoepithelial carcinoma. Moreover, by invasive phase, most were
      frankly invasive carcinoma. Recurrence was observed in seven out of 24 patients
      with outcome information available, and all were invasive cases. All seven
      patients died of causes related to the disease. The distributions of cases
      according to age, gender, tumour location, and clinical stage were similar to
      those reported in the literature. Frankly invasive cases presented a worse
      prognosis. More information is needed to further our understanding of the clinico
      pathological aspects of CXPA.

PMID- 23561263
TI  - The marine toxin okadaic acid induces alterations in the expression level of
      cancer-related genes in human neuronal cells.
AB  - Okadaic acid (OA) is one of the most common and highly distributed marine toxins.
      It can be accumulated in several molluscs and other marine organisms and cause
      acute gastrointestinal symptoms after oral consumption by humans, called
      diarrheic shellfish poisoning. However other toxic effects beyond these
      gastrointestinal symptoms were also reported. Thus, OA was found to induce
      important chromosomal abnormalities and other genetic injuries that can lead to
      severe pathologies, including cancer. Furthermore, the relationship between OA
      and carcinogenic processes has been previously demonstrated in in vivo studies
      with rodents, and also suggested in human epidemiological studies. In this
      context, further research is required to better understand the underlying
      mechanisms of OA-related tumourigenesis. In a previous study, we identified 247
      genes differentially expressed in SHSY5Y neuroblastoma cells exposed to 100nM OA
      at different times (3, 24 and 48h) by means of suppression subtractive
      hybridization. These genes were involved in relevant cell functions such as
      signal transduction, cell cycle, metabolism, and transcription and translation
      processes. However, due to the high potential percentage of false positives that
      may be obtained by this approach, results from SSH are recommended to be analyzed
      by an independent method. In the present study, we selected ten genes related to
      cancer initiation or progression, directly or indirectly, for further
      quantitative PCR analysis (ANAPC13, PTTG1, CALM2, CLU, HN1, MALAT1, MAPRE2,
      MLLT11, SGA-81M and TAX1BP1). Results obtained showed important alterations in
      the expression patterns of all the genes evaluated at one or more treatment
      times, providing, for the first time, a possible explanation at the molecular
      level of the potential relationship between the consumption of OA-contaminated
      shellfish and the incidence of different cancers in humans. Nevertheless, given
      the complexity of this process, more exhaustive studies are required before
      drawing any final conclusion.

PMID- 23561264
TI  - In vitro cytotoxicity assessment of imidazolium ionic liquids: biological effects
      in fish Channel Catfish Ovary (CCO) cell line.
AB  - Increasing interest in the application of ionic liquids as green replacement for
      volatile organic solvents emphasized the need for the evaluation of their toxic
      effects at different biological systems in order to reduce the risk for human
      health and environment. To our knowledge, effects of imidazolium ionic liquids on
      cellular level of fish cell lines have not been studied yet. The cytotoxicity of
      imidazolium ionic liquids containing different anions and alkyl chain lengths as
      the substituent at the cation ring towards the fish CCO cell line was determined
      by WST-1 proliferation assay. Morphological alterations were examined by
      fluorescent microscopy using acridine orange/ethidium bromide staining and flow
      cytometry analysis was also performed. The results showed concentration-dependent
      cytotoxicity of ionic liquids in CCO cells, related to the type of anion and
      alkyl chain length, while EC50 values showed moderate to high cytotoxicity of
      tested imidazolium ionic liquids. Distinct morphological changes observed under
      fluorescence microscope and data obtained by flow cytometry suggest that the
      toxicity of imidazolium ionic liquids with longer alkyl chains could be related
      to necrosis. Results presented in here may be helpful for filling existing gaps
      of knowledge about ionic liquids toxicity and their impact on aquatic
      environment.

PMID- 23561265
TI  - Are heat warning systems effective?
AB  - Heatwaves are associated with significant health risks particularly among
      vulnerable groups. To minimize these risks, heat warning systems have been
      implemented. The question therefore is how effective these systems are in saving
      lives and reducing heat-related harm. We systematically searched and reviewed 15
      studies which examined this. Six studies asserted that fewer people died of
      excessive heat after the implementation of heat warning systems. Demand for
      ambulance decreased following the implementation of these systems. One study also
      estimated the costs of running heat warning systems at US$210,000 compared to the
      US$468 million benefits of saving 117 lives. The remaining eight studies
      investigated people's response to heat warning systems and taking appropriate
      actions against heat harms. Perceived threat of heat dangers emerged as the main
      factor related to heeding the warnings and taking proper actions. However,
      barriers, such as costs of running air-conditioners, were of significant concern,
      particularly to the poor. The weight of the evidence suggests that heat warning
      systems are effective in reducing mortality and, potentially, morbidity. However,
      their effectiveness may be mediated by cognitive, emotive and socio-demographic
      characteristics. More research is urgently required into the cost-effectiveness
      of heat warning systems' measures and improving the utilization of the services.

PMID- 23561266
TI  - The influence of the inactives subset generation on the performance of machine
      learning methods.
AB  - BACKGROUND: A growing popularity of machine learning methods application in
      virtual screening, in both classification and regression tasks, can be observed
      in the past few years. However, their effectiveness is strongly dependent on many
      different factors. RESULTS: In this study, the influence of the way of forming
      the set of inactives on the classification process was examined: random and
      diverse selection from the ZINC database, MDDR database and libraries generated
      according to the DUD methodology. All learning methods were tested in two modes:
      using one test set, the same for each method of inactive molecules generation and
      using test sets with inactives prepared in an analogous way as for training. The
      experiments were carried out for 5 different protein targets, 3 fingerprints for
      molecules representation and 7 classification algorithms with varying parameters.
      It appeared that the process of inactive set formation had a substantial impact
      on the machine learning methods performance. CONCLUSIONS: The level of chemical
      space limitation determined the ability of tested classifiers to select
      potentially active molecules in virtual screening tasks, as for example DUDs
      (widely applied in docking experiments) did not provide proper selection of
      active molecules from databases with diverse structures. The study clearly showed
      that inactive compounds forming training set should be representative to the
      highest possible extent for libraries that undergo screening.

PMID- 23561267
TI  - Transmission of shiga toxin-producing Escherichia coli O104:H4 at a family party
      possibly due to contamination by a food handler, Germany 2011.
AB  - We investigated a cluster of shiga toxin-producing Escherichia coli (STEC)
      O104:H4 infections after a family party during a large STEC O104:H4 outbreak in
      Germany. To identify the vehicle we conducted a retrospective cohort study. Stool
      samples of party guests, and food and environmental samples from the catering
      company were tested for STEC. We defined cases as party guests with
      gastrointestinal symptoms and laboratory-confirmed STEC infection. We found 23
      cases among 71 guests. By multivariable analysis consumption of salmon [odds
      ratio (OR) 15, 95% confidence interval (CI) 2.3-97], herb cream (OR 6.5, 95% CI
      1.3-33) and bean salad (OR 6.1, 95% CI 1.4-26) were associated with STEC
      infection. STEC O104:H4 was detected in samples of bell pepper and salmon. The
      food handler developed STEC infection. Our results point towards transmission via
      several food items contaminated by a food handler. We recommend regular education
      of food handlers emphasizing their role in transmitting infectious diseases.

PMID- 23561268
TI  - Heritability of health-related quality of life: SF-12 summary scores in a
      population-based nationwide twin cohort.
AB  - AIM: The present study aims to estimate the relative importance of genetic and
      environmental factors for health-related quality of life (HRQL) measured by the
      12-item Short-Form Health Survey (SF-12). METHODS: The study was based on two
      Danish twin cohorts (46,417 twin individuals) originating from the nationwide,
      population-based Danish Twin Registry. The twins were approached by a mailed-out
      questionnaire in 2002. The questionnaire included the SF-12, information on
      demographic factors, and questions on a variety of specific diseases.
      Heritability of the SF-12 includes the physical component summary (PCS) and the
      mental component summary (MCS); and etiologically important variance components
      were estimated using multivariate biometric models. The respondents were
      stratified into six groups, based on age and sex. RESULTS: A total of 33,794
      (73%) individual twins responded to the survey. The SF-12 was completed by 29,619
      individuals, which included 9,120 complete twin pairs. Overall, the best-fitting
      model explaining the variance of HRQL was the ACE model. The estimated
      heritability of the SF-12 was between 11% and 35%, whereas between 65% and 89%
      could be explained by unique environmental or stochastic factors in the different
      sex and age groups. The highest heritability was seen among older twins. In
      addition, the genetic correlation between MCS and PCS scores was low (0.07 and
      0.23 for males and females, respectively) among younger and high (0.26 and 0.45
      for males and females, respectively) in the oldest age group. Both the largest
      genetic influence on HRQL and the largest genetic overlap between the scores were
      seen in the oldest age group, which consisted of twins older than 55. The unique
      environmental correlation between MCS and PCS were generally negative.
      CONCLUSION: The heritability of HRQL differs between different age groups. In
      general, most of the variance in the SF-12 summary components was determined by
      unique environmental factors.

PMID- 23561269
TI  - Neonicotinic analogues: selective antagonists for alpha4beta2 nicotinic
      acetylcholine receptors.
AB  - Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has
      been extensively used as a template for the synthesis of alpha4beta2-preferring
      nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and
      synthesise novel alpha4beta2-preferring neonicotinic ligands. We increased the
      distance between the basic nitrogen and aromatic group of nicotine by introducing
      an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we
      introduced a benzyloxy group linked to the benzoyl moiety. Although the
      neonicotinic compounds fully inhibited binding of both [alpha-(125)I]bungarotoxin
      to human alpha7 nAChRs and [(3)H]cytisine to human alpha4beta2 nAChRs, they were
      markedly more potent at displacing radioligand binding to human alpha4beta2
      nAChRs than to alpha7 nAChRs. Functional assays showed that the neonicotinic
      compounds behave as antagonists at alpha4beta2 and alpha4beta2alpha5 nAChRs.
      Substitutions on the aromatic ring of the compounds produced compounds that
      displayed marked selectivity for alpha4beta2 or alpha4beta2alpha5 nAChRs. Docking
      of the compounds on homology models of the agonist binding site at the
      alpha4/beta2 subunit interfaces of alpha4beta2 nAChRs suggested the compounds
      inhibit function of this nAChR type by binding the agonist binding site.

PMID- 23561270
TI  - Lost in translation: a cautionary note about presentation of non-English measures
      in English-language journals.

PMID- 23561271
TI  - Attentional processing of other's facial display of pain: an eye tracking study.
AB  - The present study investigated the role of observer pain catastrophizing and
      personal pain experience as possible moderators of attention to varying levels of
      facial pain expression in others. Eye movements were recorded as a direct and
      continuous index of attention allocation in a sample of 35 undergraduate students
      while viewing slides presenting picture pairs consisting of a neutral face
      combined with either a low, moderate, or high expressive pain face. Initial
      orienting of attention was measured as latency and duration of first fixation to
      1 of 2 target images (i.e., neutral face vs pain face). Attentional maintenance
      was measured by gaze duration. With respect to initial orienting to pain,
      findings indicated that participants reporting low catastrophizing directed their
      attention more quickly to pain faces than to neutral faces, with fixation
      becoming increasingly faster with increasing levels of facial pain expression. In
      comparison, participants reporting high levels of catastrophizing showed
      decreased tendency to initially orient to pain faces, fixating equally quickly on
      neutral and pain faces. Duration of the first fixation revealed no significant
      effects. With respect to attentional maintenance, participants reporting high
      catastrophizing and pain intensity demonstrated significantly longer gaze
      duration for all face types (neutral and pain expression), relative to low
      catastrophizing counterparts. Finally, independent of catastrophizing, higher
      reported pain intensity contributed to decreased attentional maintenance to pain
      faces vs neutral faces. Theoretical implications and further research directions
      are discussed.

PMID- 23561272
TI  - Expression analysis of efflux pump genes among drug-susceptible and multidrug
      resistant Mycobacterium tuberculosis clinical isolates and reference strains.
AB  - Finding a gene or genes that are involved with multidrug resistance will be
      useful for finding a new target for the treatment of drug resistant tuberculosis.
      In this study, we aimed to compare the differences of the expression of 15
      putative multidrug efflux pump genes in clinically isolated drug sensitive and
      multidrug resistant (MDR) Mycobacterium tuberculosis isolates, and reference
      strains. We found that these genes in the drug-sensitive and MDR M. tuberculosis
      isolates have similar rates of expressions. However, we found the expression
      levels of the all the genes are significantly higher in the clinical strains
      compared to the expression level of genes in the reference strains. In addition
      to this, it is found that standard strain has lower MIC value for the drugs
      including streptomycin and rifampin compared to the clinical isolate. We presume
      that the increase of the gene expression in the clinical strains is due to the
      exposure of antituberculosis drugs during treatment of patients, which cause
      constitutive expression of efflux systems, which might increase MIC levels of the
      major anti-tuberculosis drugs.

PMID- 23561273
TI  - Characterization of mutations in multi- and extensive drug resistance among
      strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea.
AB  - In order to characterize molecular mechanisms of first- and second-line drug
      resistance in Mycobacterium tuberculosis and to evaluate the use of molecular
      markers of resistance, we analyzed 62 multidrug-resistant, 100 extensively drug
      resistant, and 30 pan-susceptible isolates from Korean tuberculosis patients.
      Twelve genome regions associated with drug resistance, including katG, ahpC, and
      inhA promoter for isoniazid (INH); embB for ethambutol (EMB), rpoB for rifampin
      (RIF), pncA for pyrazinamide (PZA), gyrA for fluoroquinolones; rpsL, gidB, and
      rrs for streptomycin; rrs and eis for kanamycin (KM); rrs and tylA for
      capreomycin (CAP); and rrs for amikacin (AMK) were amplified simultaneously by
      polymerase chain reaction, and the DNA sequences were determined. We found
      mutations in 140 of 160 INH-resistant isolates (87.5%), 159 of 162 RIF-resistant
      isolates (98.15%), 127 of 143 EMB-resistant isolates (88.8%), 108 of 123
      ofloxacin-resistant isolates (87.8%), and 107 of 122 PZA-resistant isolates
      (87.7%); 43 of 51 STM-resistant isolates (84.3%), 15 of 17 KM-resistant isolates
      (88.2%), and 14 of 15 (AMK and CAP)-resistant isolates (93.3%) had mutations
      related to specific drug resistance. In addition, the sequence analyses of the
      study revealed many novel mutations involving these loci. This result suggests
      that mutations in the rpoB531, katGSer315Thr, and C-15T in the inhA promoter
      region, and gyrA94, embB306, pncA159, rpsL43, and A1401G in the rrs gene could
      serve as useful markers for rapid detection of resistance profile in the clinical
      isolates of M. tuberculosis in Korea, with potentials for the new therapeutic
      benefits in actual clinical practice.

PMID- 23561274
TI  - Care for place: the contributions older people make to their communities.
AB  - Older people are often positioned as passive recipients of care and dependent on
      resources or as overly productive and active. In this paper, we seek a more
      nuanced, middle ground between such stereotypes, by exploring the question: what
      contributions do older people make to the places they live in? Drawing on
      qualitative research from Aotearoa New Zealand, involving focus groups and
      interviews, we examine the varied and active ways many older people are involved
      in and contribute to their neighbourhoods and communities, or what we term 'care
      for place'. In particular, we identify the different forms of older people's care
      for place, including volunteering, activism, advocacy, and nurturing, and
      consider how these efforts positively impact on older people and the communities
      in which they live. Whilst we caution against assumptions that all older people
      should be productively involved, we argue that greater understanding of older
      people's care for place is central to challenging stereotypes of older people as
      either passive and dependent, or highly active.

PMID- 23561275
TI  - "My nest is full:" intergenerational relationships at midlife.
AB  - Incorporating a life course perspective, this qualitative study used focus groups
      to explore the experiences of midlife adults who were simultaneously providing
      support to emerging adult children and aging parents. Results indicated that
      adults situated in middle generations held beliefs that endorsed family-based
      responsibility to both younger and older members. Parents gladly supported
      children despite their longer transition to adulthood. Often unanticipated but
      accepted, provisions of care to aging parents were experienced with ambivalence -
      a joy and a burden. The transition of their parents to greater dependence helped
      participants gain insights into the terrain of late life and encouraged
      reflections about the intersection of aging, independence, and family
      responsibility. Participants expressed intentions to preserve their own
      independence and spare their children of caregiving burdens through self-directed
      actions. Implications focused on negotiations of family relationships around
      issues of independence and family responsibilities as a way to reduce
      intergenerational ambivalence.

PMID- 23561276
TI  - Financial worry among older people: who worries and why?
AB  - This study sought to clarify what drives economic worries among older people.
      Based upon the data from a national sample of adults aged 65 and older in Israel
      (N=550), we examined associations between financial worry and economic status,
      lifestyle, social network, concerns about functional health, long term care needs
      and cognition, and population group. The main financial worry was that pension
      funds will not suffice for one's entire life. Multivariate analysis revealed that
      financial worry was negatively related to perceived income adequacy and age, and
      positively related to concerns about care and to apprehensions regarding one's
      ability to make decisions. Immigrants from the former Soviet Union were found to
      worry less. Understanding the different sources of financial worries among older
      people is essential insofar as older people are increasingly expected to take
      personal responsibility for their financial futures. Dealing with negative
      outcomes that stem from financial worries are important programming and policy
      goals in an era of population aging.

PMID- 23561277
TI  - Same sex acts involving older men. An ethnographic study.
AB  - For many men in modern Western societies it is not uncommon to have anonymous
      same-sex acts in cruising places with a varying frequency depending on many
      factors, e.g. their biographical history, marital status, religion, and age. This
      paper looks at generational differences in the Italian gay community and
      specifically contrasts both setting and patterns of social interaction of two
      cohorts of men (older men and younger adults) patronizing bathhouses. The meaning
      of adult development and aging of sexual minorities is little understood in
      Italy. For the first time in history, a generation of self-identified gay men is
      approaching retirement, and yet we do not understand what well-being and
      successful development in later life mean in this community. Moreover, the aging
      processes among gay men who are already in their retirement years, many of whom
      are still "closeted," remain invisible. The ethnographic report, based on two
      years of participant observation, reveals the culture of the gay bath and the
      social and sexual spaces of older and younger gay men and their self-definitions
      and relationship to the "gay community".

PMID- 23561278
TI  - A day to be lived. Elderly peoples' possessions for everyday life in assisted
      living.
AB  - This study is a qualitative interview study about the household possessions that
      elderly women and men brought with them when moving into assisted living. The
      move implied a substantial reduction of their possessions since, in all cases,
      they had left a larger dwelling than the one they moved to. The study gives a
      glimpse into the everyday life of the oldest old in assisted living. The things
      the elderly participants brought were of three types; cherished objects,
      representations of who they were, and mundane objects. The most important objects
      indicated by the elderly often belonged to the third type, and were preferred for
      the significance they had for the everyday life of the individual. These objects
      revealed a circumscribed but dignified life in their private bed-sitting room,
      often in solitude, where the elderly individuals pursued various interests and
      small-scale activities. However, this life was organized and preferred by the
      individuals themselves, in accordance with the principles of resident autonomy
      and individual choice that are promoted in assisted living. The author suggests
      that these self-engaged pursuits can contribute to bridging the gap between
      disengagement and activity theories. The study results also contribute to making
      visible the private life of the oldest old in assisted living.

PMID- 23561279
TI  - Being central to decision making means I am still here!: the essence of decision
      making for people with dementia.
AB  - The ability to make choices and decisions, and to have those decisions upheld, is
      central to self-determination. For people living with a diagnosis of dementia,
      however, it can be difficult to remain involved in decision making. While many
      studies show that people with mild or moderate dementia have the ability to
      participate in decision making, there are also indications that the attitudes of
      those around them, including health professionals and family carers, can
      sometimes be a barrier, and there is generally little understanding about the
      nature of decision making for this population. This small pilot study draws on
      van Manen's approach to phenomenology to explore the essence of decision making
      for people living with dementia. The findings highlight the importance of
      remaining central to decision making, and the key role that subtle support from
      carers plays in enabling this.

PMID- 23561280
TI  - Canadians' support for radical life extension resulting from advances in
      regenerative medicine.
AB  - This paper explores Canadian public perceptions of a hypothetical scenario in
      which a radical increase in life expectancy results from advances in regenerative
      medicine. A national sample of 1231 adults completed an online questionnaire on
      stem cell research and regenerative medicine, including three items relating to
      the possibility of Canadians' average life expectancy increasing to 120 years by
      2050. Overall, Canadians are strongly supportive of the prospect of extended
      lifespans, with 59% of the sample indicating a desire to live to 120 if
      scientific advances made it possible, and 47% of respondents agreeing that such
      increases in life expectancy are possible by 2050. The strongest predictors of
      support for radical life extension are individuals' general orientation towards
      science and technology and their evaluation of its plausibility. These results
      contrast with previous research, which has suggested public ambivalence for
      biomedical life extension, and point to the need for more research in this area.
      They suggest, moreover, that efforts to increase public awareness about anti
      aging research are likely to increase support for the life-extending consequences
      of that research program.

PMID- 23561281
TI  - Relationship goals of middle-aged, young-old, and old-old Internet daters: an
      analysis of online personal ads.
AB  - PURPOSE OF THE STUDY: Research on courtship patterns and romantic relationship in
      later life has not kept pace with the burgeoning number of older adults
      interested in dating. DESIGN AND METHODS: We conducted content analyses of themes
      arising from 450 personal ads written by middle-aged (40-54), young-old (60-74),
      and old-old (75+) participants. RESULTS: Significant differences between the
      young-old and the middle-aged were few; those between the young-old and old-old
      were numerous. Compared to the old-old, the young-old and middle-aged were more
      likely to mention adventure, romance, sexual interests, and seeking a soul mate
      and less likely to mention health. IMPLICATIONS: This study increases our
      understanding of relationship goals in later life and highlights the error of
      treating all older adults as a homogeneous group. Practice and policy can benefit
      from more nuanced distinctions between age groups and an enhanced recognition of
      the vibrant emotional, romantic, and sexual lives of older adults.

PMID- 23561282
TI  - The notion of precariousness among older adults living alone in the U.S.
AB  - This paper argues that older adults living alone in the U.S. face a set of unique
      challenges, as they are likely to experience a sense of precariousness. The term
      precariousness points to an intrinsic sense of instability and insecurity
      stemming from a lack of, or difficulty to, access essential resources. During a
      two-year ethnography of 47 older solo dwellers, this term captured one of the
      distinctive traits of the experience of living alone in older age in the U.S. The
      findings from semi-structured interviews and participant observation highlight
      the emergence of the notion of precariousness along three levels of analysis.
      First, on the micro and subjective level of analysis, older solo dwellers may
      struggle to perform the chores related to their household as they may deal with a
      failing body, faltering memory, and fixed if not shrinking income. Second, on the
      meso and institutional level of analysis, older adults living alone need to
      navigate the complex, scattered, and ever-changing landscape of services and
      understand their eligibility criteria, accessibility, fees, and conditions. At
      the same time they may have to deal with family issues. Finally, the macro level
      examines the pressure on older solo dwellers of a prevalent ideology that prizes
      independent behaviors and personal responsibility. In conclusion, the notion of
      precariousness illustrates the unique position of older adults living alone as
      they face different type of challenges on a micro, meso, and macro dimension. The
      paper ends with an invitation to create social policies that accommodate the
      needs of a growing number of older adults living alone.

PMID- 23561283
TI  - The utility of positioning theory to the study of ageing: Examples from research
      with childless older people.
AB  - Growing older is hard to make sense of. Opposing perspectives are presented on
      everything from individual to population ageing, and there is widespread
      ambivalence towards many aspects of ageing. Positioning theory is a research
      approach that can tolerate such ambiguity and provides a clear, useful framework
      to make sense of research data, while doing justice to its complexity. It is
      starting to be used in gerontology; the aim of this paper is to give
      gerontologists the tools and impetus to use it more. The positioning triad is
      outlined, comprising positions (how we position ourselves and others within a
      single conversation or across a lifetime), storylines (the individual and social
      narratives which furnish those positions), and the speech acts (and acts of
      research) through which storylines and positions are enacted. In addition,
      considering the rights and duties associated with different positions and
      storylines can usefully illuminate some of the tensions around competing
      positions on ageing. Worked examples from a qualitative study on childless older
      people (38 participants aged 63 to 93) in terms of their positioning of
      childlessness, views on residential care, and positioning of emotional support
      show how the complexity of such diverse topics can be usefully studied using a
      positioning theory framework.

PMID- 23561284
TI  - The making of 'the elderly': constructing the subject of care.
AB  - The provision and arrangement of care for elderly people is one of the main
      challenges for the future of European welfare states. In both political and
      public discourses elderly people feature as the subjects who are associated with
      particular needs, wishes and desires and for whom care needs to be guaranteed and
      organised. Underlying the cultural construction of the care regime and culture is
      an ideal type model of the elderly person. This paper analyses the discursive
      construction of elderly people in the discourses on care in Austria. An
      understanding of how elderly people as subjects, their wishes and needs and their
      position within society are constructed enables us to analyse, question and
      challenge the current dominant care arrangements and its cultural embeddings. The
      paper demonstrates the processes of silencing, categorisation and passivation of
      elderly people and it is argued that the socio-discursive processes lead to a
      particular image of the elderly person which consequently serves as the basis on
      which the care regime is built.

PMID- 23561285
TI  - Transnational connections of later-life migrants.
AB  - In this paper a transnational perspective is used to explain whether and how
      older migrants construct and sustain their social networks. The paper uses a
      transnational viewpoint on older migrants' lives by analysing their engagement
      with their former homeland, and the intensity and habitualness of those
      engagements in old age. The aim of this article is to study the transnational
      connections of later-life migrants'. Attention is especially paid to the features
      of old age while maintaining these connections. These considerations are based on
      analyses of transnational networks in the everyday lives of later-life migrants
      from the former Soviet Union residing in Finland. The data were collected from 11
      later-life migrants. It is found that transnational relationships are a vital
      part of the everyday lives of older migrants, and that they are sustained in
      varied ways. These connections mean a concrete source of help, family
      affiliations, the sharing of emotions, and a larger social network. Economic
      limitations affect the frequency and type of communication, and various physical
      limitations may also cause inability to maintain contacts across borders. In
      these circumstances, family members or other close relatives or friends are
      needed to deliver messages on the older person's behalf. Old age and immigration
      status affect the amount and direction of communication across borders, thereby
      shaping these networks.

PMID- 23561286
TI  - Neurophysiological activity underlying altered brain metabolism in epileptic
      encephalopathies with CSWS.
AB  - We investigated the neurophysiological correlate of altered regional cerebral
      glucose metabolism observed in children with epileptic encephalopathy with
      continuous spike-waves during sleep (CSWS) by using a multimodal approach
      combining time-sensitive magnetic source imaging (MSI) and positron emission
      tomography with [(18)F]-fluorodeoxyglucose (FDG-PET). Six patients (4 boys and 2
      girls, age range: 4-8 years, 3 patients with Landau-Kleffner syndrome (LKS), 3
      patients with atypical rolandic epilepsy (ARE)) were investigated by FDG-PET and
      MSI at the acute phase of CSWS. In all patients, the onset(s) of spike-waves
      discharges were associated with significant focal hypermetabolism. The
      propagation of epileptic discharges to other brain areas was associated with
      focal hypermetabolism (five patients), hypometabolism (one patient) or the
      absence of any significant metabolic change (one patient). Interestingly, most of
      the hypometabolic areas were not involved in the epileptic network per se. This
      study shows that focal hypermetabolism observed at the acute phase of CSWS are
      related to the onset or propagation sites of spike-wave discharges. Spike-wave
      discharges propagation can be associated to other types of metabolic changes,
      suggesting the occurrence of various neurophysiological mechanisms at the
      cellular level. Most of the hypometabolic areas are not involved in the epileptic
      network as such and are probably related to a mechanism of remote inhibition.
      These findings highlight the critical value of combining FDG-PET with time
      sensitive functional neuroimaging approaches such as MSI to assess CSWS epileptic
      network when surgery is considered as a therapeutic approach.

PMID- 23561287
TI  - A pilot study assessing the bioavailability and pharmacokinetics of diazepam
      after intranasal and intravenous administration in healthy volunteers.
AB  - Diazepam rectal gel (Diastat((r))) is the only FDA-approved product indicated for
      acute repetitive seizures. Despite its proven efficacy, most older children and
      adults object to this route of administration. As a result, many patients do not
      realize the benefit of a therapy that can improve outcomes and decrease
      healthcare costs. Intranasal administration of benzodiazepines offers a potential
      alternative. The primary objective of this study was to compare the
      bioavailability and pharmacokinetics of two novel intranasal (IN) diazepam (DZP)
      formulations versus intravenous (IV) administration in healthy volunteers. Twenty
      four healthy volunteers were randomized into an open-label, three-way crossover
      study. 10mg doses of two investigational intranasal DZP formulations (solution,
      suspension) and a 5mg IV dose of commercially available DZP injectable, USP were
      given. A two-week washout period separated treatments. Plasma samples for DZP
      analysis were collected pre-dose and at regular intervals up to 240 h post-dose.
      DZP concentration-time data were analyzed using a non-compartmental
      pharmacokinetics approach. Exposure following administration of DZP IN solution
      (absolute bioavailability - 97%) was greater than the IN suspension (absolute
      bioavailability - 67%). Mean Cmaxvalues for the suspension and solution
      formulations were 221 ng/mL and 272 ng/mL, respectively. Median time to maximum
      concentration (Tmax) was 1h and 1.5h for suspension and solution formulation,
      respectively. Both investigational intranasal formulations were well tolerated.
      The results of this pilot study indicate that development of an intranasal
      diazepam formulation with high bioavailability, reasonable variability, and good
      tolerability is feasible.

PMID- 23561288
TI  - Non operative management of abdominal trauma - a 10 years review.
AB  - INTRODUCTION: Due to high rate of operative mortality and morbidity non-operative
      management of blunt liver and spleen trauma was widely accepted in stable
      pediatric patients, but the general surgeons were skeptical to adopt it for
      adults. The current study is analysis of so far largest sample (1071) of
      hemodynamically stable blunt liver, spleen, kidney and pancreatic trauma patients
      managed non operatively irrespective of severity of a single /multiple solid
      organ injury or other associated injuries with high rate of success. METHODS:
      Experience of 1071 blunt abdominal trauma patients treated by NOM at a tertiary
      care National Trauma Centre in Oman (from Jan 2001 to Dec 2011) was reviewed,
      analyzed to determine the indications, methods and results of NOM. Hemodynamic
      stability along with ultra sound, CT scan and repeated clinical examination were
      the sheet anchors of NOM. The patients were grouped as (1) managed by NOM
      successfully, (2) failure of NOM and (3) directly subjected to surgery. RESULTS:
      During the 10 year period, 5400 polytrauma patients were evaluated for abdominal
      trauma of which 1285 had abdominal injuries, the largest sample study till date.
      Based on initial findings 1071 patients were admitted for NOM. Out of 1071
      patients initially selected 963 (89.91%) were managed non operatively, the
      remaining 108 (10.08%) were subjected to laparotomy due to failure of NOM.
      Laparotomy was performed on 214(19.98%) patients as they were unstable on
      admission or had evidence of hollow viscous injury. CONCLUSION: NOM for blunt
      abdominal injuries was found to be highly successful in 89.98% of the patients in
      our study. Management depended on clinical and hemodynamic stability of the
      patient. A patient under NOM should be admitted to intensive care / high
      dependency for at least 48-72 hours for close monitoring of vital signs, repeated
      clinical examinations and follow up investigations as indicated.

PMID- 23561289
TI  - Haptic feedback and control of a flexible surgical endoscopic robot.
AB  - A flexible endoscope could reach the potential surgical site via a single small
      incision on the patient or even through natural orifices, making it a very
      promising platform for surgical procedures. However, endoscopic surgery has
      strict spatial constraints on both tool-channel size and surgical site volume. It
      is therefore very challenging to deploy and control dexterous robotic instruments
      to conduct surgical procedures endoscopically. Pioneering endoscopic surgical
      robots have already been introduced, but the performance is limited by the
      flexible neck of the robot that passes through the endoscope tool channel. In
      this article we present a series of new developments to improve the performance
      of the robot: a force transmission model to address flexibility, elongation study
      for precise position control, and tissue property modeling for haptic feedback.
      Validation experiment results are presented for each sector. An integrated
      control architecture of the robot system is given in the end. 

PMID- 23561290
TI  - Virus-like particles: promising platforms with characteristics of DIVA for
      veterinary vaccine design.
AB  - In general, it is difficult to differentiate infected from vaccinated animals
      through vaccination with conventional vaccines, thereby impeding the serological
      surveillance of animal diseases. DIVA (differentiating infected from vaccinated
      animals) vaccine, originally known as marker vaccine, usually based on the
      absence of at least one immunogenic protein in the vaccine strain, allows DIVA in
      conjunction with a diagnostic test that detects antibodies against the antigens
      lacking in the vaccine strain. Virus-like particles (VLPs), composed of one or
      more structural proteins but no genomes of native viruses, mimic the organization
      and conformation of authentic virions but have no ability to self-replicate in
      cells, potentially yielding safer vaccine candidates. Since VLPs containing
      either monovalent or multivalent antigen can be produced in compliance with the
      requirements for serological surveillance, the use of VLP-based vaccines plays a
      promising role in DIVA vaccination strategies against animal diseases. Here, we
      critically reviewed VLPs and companion diagnostics with properties of DIVA for
      veterinary vaccine design, and three different VLPs as promising platforms for
      DIVA vaccination strategies in animals.

PMID- 23561292
TI  - Value of multimodality monitoring using brainstem auditory evoked potentials and
      somatosensory evoked potentials in endoscopic endonasal surgery.
AB  - OBJECTIVES: To evaluate the value of intraoperative neurophysiological monitoring
      (IONM) using brainstem auditory evoked potential (BAEP) and somatosensory evoked
      potential (SSEP) monitoring to predict and/or prevent postoperative neurological
      deficits during endoscopic endonasal surgery (EES). METHODS: We retrospectively
      identified 138 consecutive patients who had BAEP monitoring in addition to SSEP
      monitoring during EES at our institution. We reviewed the postoperative clinical
      outcomes and neurophysiological changes independently. RESULTS: The total of
      number of patients with any IONM changes was 10. The incidence of BAEP changes
      was 3.62%. The incidence of SSEP changes was 3.62% as well. One patient had
      changes in both BAEPs and SSEPs. Majority of the changes were observed during
      changes in mean arterial pressure (MAP) without any postoperative neurological
      deficits. There were two postoperative neurological deficits. DISCUSSION: BAEPs
      and SSEPs provide unique information about integrity of brainstem function during
      EES procedures involving tumors in the and around clival region. We advocate a
      comprehensive multimodality approach to IONM during EESs including BAEPs and
      SSEPs depending on the location of the neural structures at risk.

PMID- 23561294
TI  - Generation of a luciferase-based reporter for CHH and CG DNA methylation in
      Arabidopsis thaliana.
AB  - BACKGROUND: DNA methylation ensures genome integrity and regulates gene
      expression in diverse eukaryotes. In Arabidopsis, methylation occurs in three
      sequence contexts: CG, CHG and CHH. The initial establishment of DNA methylation
      at all three sequence contexts occurs through a process known as RNA-directed DNA
      methylation (RdDM), in which small RNAs bound by Argonaute4 (AGO4) guide DNA
      methylation at homologous loci through the de novo methyltransferase DRM2. Once
      established, DNA methylation at each of the three sequence contexts is maintained
      through different mechanisms. Although some players involved in RdDM and
      maintenance methylation have been identified, the underlying molecular mechanisms
      are not fully understood. To aid the comprehensive identification of players in
      DNA methylation, we generated a transgenic reporter system that permits genetic
      and chemical genetic screens in Arabidopsis. RESULTS: A dual 35S promoter (d35S)
      driven luciferase (LUC) reporter was introduced into Arabidopsis and LUCL, a line
      with a low basal level of luciferase activity, was obtained. LUCL was found to be
      a multi-copy, single-insertion transgene that contains methylated cytosines in
      CG, CHG and CHH contexts, with the highest methylation in the CG context.
      Methylation was present throughout the promoter and LUC coding region. Treatment
      with an inhibitor of cytosine methylation de-repressed luciferase activity. A
      mutation in MET1, which encodes the CG maintenance methyltransferase, drastically
      reduced CG methylation and de-repressed LUC expression. Mutations in AGO4 and
      DRM2 also de-repressed LUC expression, albeit to a smaller extent than loss of
      MET1. Using LUCL as a reporter line, we performed a chemical screen for compounds
      that de-repress LUC expression, and identified a chemical, methotrexate, known to
      be involved in biogenesis of the methyl donor. CONCLUSION: We developed a
      luciferase-based reporter system, LUCL, which reports both RdDM and CG
      maintenance methylation in Arabidopsis. The low basal level of LUCL expression
      provides an easy readout in genetic and chemical genetic screens that will
      dissect the mechanisms of RdDM and methylation maintenance.

PMID- 23561295
TI  - A brief version of the Subjects' Response to Antipsychotics questionnaire to
      evaluate treatment effects.
AB  - BACKGROUND: Monitoring patients' experiences with antipsychotics may help to
      improve medication adherence and outcome. We aimed to develop a shorter version
      of a comprehensive 74-item self-report questionnaire suitable for routine
      monitoring of desired and undesired effects of antipsychotics. METHODS: Included
      were patients with psychotic disorders from seven mental health care
      organizations in The Netherlands, using antipsychotic medication, who completed
      the Subjects' Response to Antipsychotics (SRA-74). Exploratory factor analysis
      (EFA) and similarity analysis based on mutual information were used to identify
      the latent factor structure of the SRA. Items were reduced according to their
      metric properties and clinical relevance upon consensus by an expert panel, using
      a Delphi procedure of three rounds. We determined the internal consistency of the
      shorter version using Cronbach's alpha. RESULTS: SRA data of N=1478 patients
      (mean age of 40 years, 31% females) were eligible for analysis. EFA extracted
      thirteen factors from the SRA-74, including four factors for desired effects
      (e.g. recovery of psychosis, cognition and social functioning) and nine factors
      for undesired effects (e.g. weight gain, flattened affect and increased sleep).
      Based on this solution 12 items were eliminated for statistical reasons. The
      expert panel eliminated another 28 items with redundant content, resulting in a
      34-item version. The SRA-34 includes 10 desired and 24 clinically relevant
      undesired effects. Both the subscales for desired and undesired effects have a
      Cronbach's alpha coefficient of 0.82. CONCLUSIONS: The SRA-34 can be used to
      evaluate desired and undesired effects of antipsychotics in routine clinical
      practice and research.

PMID- 23561297
TI  - Change in jumping to conclusions linked to change in delusions in early
      psychosis.

PMID- 23561296
TI  - Endocannabinoid metabolism in the prefrontal cortex in schizophrenia.
AB  - Adolescent cannabis use is associated with greater relative risk, increased
      symptom severity, and earlier age of onset of schizophrenia. We investigated
      whether this interaction may be partly attributable to disease-related
      disturbances in metabolism of the major cortical endocannabinoid 2
      arachidonoylglycerol (2-AG). Transcript levels for the recently discovered 2-AG
      metabolizing enzyme, alpha-beta-hydrolase domain 6 (ABHD6), were assessed using
      quantitative PCR in the prefrontal cortex of schizophrenia and healthy subjects
      (n=84) and antipsychotic- or tetrahydrocannabinol-exposed monkeys. ABHD6 mRNA
      levels were elevated in schizophrenia subjects who were younger and had a shorter
      illness duration but not in antipsychotic- or tetrahydrocannabinol-exposed
      monkeys. Higher ABHD6 mRNA levels may increase 2-AG metabolism which may
      influence susceptibility to cannabis in the earlier stages of schizophrenia.

PMID- 23561298
TI  - Same ammo, different weapons: enzymatic extracts from two apple genotypes with
      contrasted susceptibilities to fire blight (Erwinia amylovora) differentially
      convert phloridzin and phloretin in vitro.
AB  - The necrogenic bacterium Erwinia amylovora responsible for the fire blight
      disease causes cell death in apple tissues to enrich intercellular spaces with
      nutrients. Apple leaves contain large amounts of dihydrochalcones (DHCs),
      including phloridzin and its aglycone phloretin. Previous work showed an
      important decrease in the constitutive DHCs stock in infected leaves, probably
      caused by transformation reactions during the infection process. At least two
      flavonoid transformation pathways have been described so far: deglucosylation and
      oxidation. The aim of the present study was to determine whether DHCs are
      differentially converted in two apple genotypes displaying contrasted
      susceptibilities to the disease. Different analyses were performed: i) enzymatic
      activity assays in infected leaves, ii) identification/quantification of end
      products obtained after in vitro enzymatic reactions with DHCs, iii) evaluation
      of the bactericidal activity of end-products. The results of the enzymatic assays
      showed that deglucosylation was dominant over oxidation in the susceptible
      genotype MM106 while the opposite was observed in the resistant genotype
      Evereste. These data were confirmed by LC-UV/Vis-MS analysis of in vitro reaction
      mixtures, especially because higher levels of o-quinoid oxidation products of
      phloretin were measured by using the enzymatic extracts of Evereste infected
      leaves. Their presence correlated well with a strong bactericidal activity of the
      reaction mixtures. Thus, our results suggest that a differential transformation
      of DHCs occur in apple genotypes with a potential involvement in the
      establishment of the susceptibility or the resistance to fire blight, through the
      release of glucose or of highly bactericidal compounds respectively.

PMID- 23561299
TI  - Ever decreasing circles: Speech production in semantic dementia.
AB  - We explored the impact of a degraded semantic system on lexical, morphological
      and syntactic complexity in language production. We analysed transcripts from
      connected speech samples from eight patients with semantic dementia (SD) and
      eight age-matched healthy speakers. The frequency distributions of nouns and
      verbs were compared for hand-scored data and data extracted using text-analysis
      software. Lexical measures showed the predicted pattern for nouns and verbs in
      hand-scored data, and for nouns in software-extracted data, with fewer low
      frequency items in the speech of the patients relative to controls. The
      distribution of complex morpho-syntactic forms for the SD group showed a reduced
      range, with fewer constructions that required multiple auxiliaries and
      inflections. Finally, the distribution of syntactic constructions also differed
      between groups, with a pattern that reflects the patients' characteristic anomia
      and constraints on morpho-syntactic complexity. The data are in line with
      previous findings of an absence of gross syntactic errors or violations in SD
      speech. Alterations in the distributions of morphology and syntax, however,
      support constraint satisfaction models of speech production in which there is no
      hard boundary between lexical retrieval and grammatical encoding. 

PMID- 23561300
TI  - Triterpenoid saponins from the roots of Gypsophila trichotoma Wender.
AB  - Eleven triterpenoid saponins were isolated from the roots of Gypsophila
      trichotoma Wender. (G. trichotoma Wender. var. trichotoma) (Caryophyllaceae),
      together with one known compound. The structures were established on the basis of
      extensive NMR analysis ((1)H, (13)C NMR, COSY, TOCSY, ROESY, HSQC, and HMBC),
      completed by analysis of HR-ESI-MS and ESI-MS(n). The saponins have the commonly
      found gypsogenin as the aglycone substituted at C-3 with trisaccharide and at C
      28 with oligosaccharide through a fucose residue, as saponins isolated from
      Gypsophila perfoliata L. originated from China. The oligosaccharide attached to C
      28 is substituted with acetyl and (or) sulfate groups. The cytotoxicity of the
      saponin extract from G. trichotoma was evaluated against a rat alveolar
      macrophage-like cell line NR8383 and human leukemia cell lines U937 and BV-173.
      The synergistic effect of the aminoacyl saponins, previously isolated from G.
      trichotoma, was tested for its ability to enhance the cytotoxicity of the
      targeted toxin in HER14 cells.

PMID- 23561301
TI  - The characterisation of xyloglucanase inhibitors from Humulus lupulus.
AB  - Phytopathogenic fungi secrete a powerful arsenal of enzymes that are potentially
      active against each polysaccharide component of the plant cell wall. To defend
      themselves, plants synthetise a variety of molecules that inhibit the activity of
      cell wall-degrading enzymes. Xyloglucan-specific endoglucanase inhibitor proteins
      (XEGIPs) act specifically against the members of fungal glycoside hydrolase
      family 12 (GH12 in the CAZy database). In the present study, we describe the
      identification of three XEGIP homologues from hop (Humulus lupulus L.). When
      incubating each of the recombinant inhibitors with an enzymatic cocktail from
      Aspergillus aculeatus (Viscozyme(r)), the xyloglucan-degrading endoglucanase
      activity decreased to 15% and 5% for HlXEGIP1 and HlXEGIP2, respectively, whereas
      no inhibition of the Viscozyme(r) enzymes was observed for the third (also called
      HlXEGIP homologue 3, or HlXEGIPh3). Fungal enzymatic cocktails from 20 different
      species also showed xyloglucan-degrading endoglucanase activities, and most of
      them were inhibited by HlXEGIP1 and -2. Furthermore, a real time RT-PCR analysis
      revealed variations in the spatial distribution of the genes encoding the three
      inhibitors and differential expression during development and (a) biotic stress.
      The role of XEGIPs in the plant-fungus interaction is discussed, and a model
      suggesting a distinct role of these XEGIP homologues is proposed: HlXEGIP1 may
      act in cases of abiotic stress, while HlXEGIP2 reacts to biotic stress, and
      physiological development may be influenced by HlXEGIPh3.

PMID- 23561302
TI  - Quantitative spin polarization analysis in photoelectron emission microscopy with
      an imaging spin filter.
AB  - Using a photoelectron emission microscope (PEEM), we demonstrate spin-resolved
      electron spectroscopic imaging of ultrathin magnetic Co films grown on Cu(100).
      The spin-filter, based on the spin-dependent reflection of low energy electrons
      from a W(100) crystal, is attached to an aberration corrected electrostatic
      energy analyzer coupled to an electrostatic PEEM column. We present a method for
      the quantitative measurement of the electron spin polarization at 4 * 103 points
      of the PEEM image, simultaneously. This approach uses the subsequent acquisition
      of two images with different scattering energies of the electrons at the W(100)
      target to directly derive the spin polarization without the need of magnetization
      reversal of the sample.

PMID- 23561303
TI  - Changes in leg pain after bilateral fasciotomy to treat chronic compartment
      syndrome: a case series study.
AB  - BACKGROUND: Intracompartmental pressure (ICP) as the diagnostic gold standard in
      the management of chronic compartment syndrome (CCS) is debated. We present a
      diagnostic protocol in which the decision to operate can be based upon clinical
      findings alone. The aim of this study was to examine whether patients who
      underwent surgery for CCS based on clinical findings experienced significant long
      term pain relief. METHODS: A standardized clinical examination, including skin
      sensitivity, was performed in patients with bilateral leg pain and/or cramps.
      Before and after a symptom-provoking step test, ICPs were measured. The primary
      outcome was self-reported leg pain measured on a visual analogue scale. Secondary
      outcomes were satisfaction with the treatment result and health-related quality
      of life (HRQL) measured with the SF-8 questionnaire. Postoperative data were
      collected after 2 years. RESULTS: Follow-up was completed for 37 of 40 patients.
      ICP was increased in 80.5% of the compartments examined before surgery, but did
      not correlate with the degree of leg pain. The remaining compartments were
      diagnosed as CCS based on clinical findings, despite ICPs below the threshold.
      Leg cramps occurred in 32 of 37 (86.5%) patients during physical activity and at
      night. Leg pain improved from a score of 8.0+/-1.5 to 2.3+/-2.1, P<0.001.
      Satisfaction with the treatment result was reported by 81.1% of the patients,
      accompanied by normalized HRQL. CONCLUSIONS: The diagnostic protocol led to a
      fasciotomy in all compartments of both legs, which was associated with
      substantial and sustained relief of leg pain, improved HRQL, and patient
      satisfaction.

PMID- 23561304
TI  - Symptom burden and quality of life in advanced non-small cell lung cancer
      patients in France and Germany.
AB  - BACKGROUND: To assess patient reported symptom burden and impact on disease
      specific health related quality of life (HRQOL) in advanced non-small cell lung
      cancer (NSCLC) patients. METHODS: Patients with advanced (stage IIIB/IV) NSCLC in
      France (n = 613) and Germany (n = 600) were recruited into a multicenter, patient
      record-based cross-sectional study. Patient reported symptoms using the Lung
      Cancer Symptom Scale, which assesses fatigue, loss of appetite, shortness of
      breath, cough, pain and blood in sputum on a 0-100 visual analog scale. Disease
      specific and generic HRQOL were assessed using the Functional Assessment of
      Cancer Therapy-Lung (FACT-L) and the EuroQol five-dimensional questionnaire (EQ
      5D) respectively. A multivariate regression analysis was performed with total
      FACT-L score as the dependent variable and symptom scores as predictors. Age,
      gender, stage and performance status were used as control variables. RESULTS:
      Majority of the patients were male (67%), Caucasian (93%) with an average age of
      63 years. Fatigue, loss of appetite, shortness of breath, cough and pain were
      reported by >= 90% of patients. The mean health utility index score was found to
      be 0.58 and the mean general health status score was 58.0. Fatigue (beta = 
      0.122; p < 0.001), loss of appetite (beta = -0.170; p < 0.001), pain (beta = 
      0.145; p < 0.001), shortness of breath (beta = -0.118; p < 0.001) were found to
      be significant predictors of lung cancer specific quality of life as measured by
      the FACT-L total score. CONCLUSION: Fatigue, loss of appetite, shortness of
      breath and pain have a significant negative impact on patient reported disease
      specific HRQOL in advanced NSCLC patients.

PMID- 23561305
TI  - Serotype and surface protein gene distribution of colonizing group B
      streptococcus in women in Egypt.
AB  - Group B streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis.
      We determined the distribution of serotypes and surface protein encoding genes of
      GBS strains from pregnant and non-pregnant women in Egypt. Vaginal swabs from 364
      women were screened by culture and 100 (27.4%) yielded GBS. Serotype V was the
      most predominant (33%), followed by serotypes II (17%), III (15%), Ia (14%), VI
      (12%), Ib (8%) and IV (1%). The most common surface protein genes were epsilon
      (27%), alp3 (26%), bca (18%), rib (16%) and alp2 (10%). Two isolates were
      negative for surface protein genes. The distribution of serotypes and surface
      proteins was similar to reports from other parts of the world but the relatively
      high frequency of serotype VI was a notable feature of the strains from women in
      Egypt.

PMID- 23561306
TI  - Exergames for health and fitness: the roles of GPS and geosocial apps.
AB  - Large numbers of children and adolescents in Canada, UK and USA are not getting
      their recommended daily dose of moderate to vigorous physical activity, and are
      thus more prone to obesity and its ill health effects. Exergames (video games
      that require physical activity to play) are rapidly gaining user acceptance, and
      may have the potential to increase physical activity levels among young people.
      Mobile exergames for GPS (global positioning system)-enabled smartphones and mini
      tablets take players outdoors, in the open air, unlike console exergames, e.g.,
      Xbox 360 Kinect exergames, which limit players to playing indoors in front of a
      TV set. In this paper and its companion 'Additional file 1', we review different
      examples of GPS exergames and of gamified geosocial apps and gadgets (mobile,
      location-aware apps and devices with social and gamification features), and
      briefly discuss some of the issues surrounding their use. Further research is
      needed to document best practices in this area, quantify the exact health and
      fitness benefits of GPS exergames and apps (under different settings and
      scenarios), and find out what is needed to improve them and the best ways to
      promote their adoption by the public.

PMID- 23561307
TI  - The dopamine beta-hydroxylase inhibitor, nepicastat, suppresses chocolate self
      administration and reinstatement of chocolate seeking in rats.
AB  - Craving for chocolate is a common phenomenon, which may evolve to an addictive
      like behaviour and contribute to obesity. Nepicastat is a selective dopamine beta
      hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of
      cocaine seeking in rats. We verified whether nepicastat was able to modify the
      reinforcing and motivational properties of a chocolate solution and to prevent
      the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg,
      intraperitoneal) produced a dose-related inhibition of operant self
      administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and
      progressive-ratio schedules of reinforcement, measures of the reinforcing and
      motivational properties of the chocolate solution, respectively. The effect of
      nepicastat on the reinstatement of chocolate seeking was studied in rats in which
      lever-responding had been extinguished by removing the chocolate solution for
      approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of
      lever-responding triggered by a 'priming' of the chocolate solution together with
      cues previously associated with the availability of the reward. In a separate
      group of food-restricted rats trained to lever-respond for regular food pellets,
      nepicastat reduced FR10 lever-responding with the same potency as for the
      chocolate solution. Spontaneous locomotor activity was not modified by nepicastat
      doses that reduced self-administration of the chocolate solution and regular food
      pellets and suppressed the reinstatement of chocolate seeking. The results
      indicate that nepicastat reduces motivation to food consumption sustained by
      appetite or palatability. Moreover, the results suggest that DBH inhibitors may
      be a new class of pharmacological agents potentially useful in the prevention of
      relapse to food seeking in human dieters.

PMID- 23561308
TI  - Female with flank pain and hypotension.

PMID- 23561309
TI  - Male patient with throat swelling and painful swallowing.

PMID- 23561310
TI  - Methamphetamine-related psychiatric visits to an urban academic emergency
      department: an observational study.
AB  - BACKGROUND: Methamphetamine, a stimulant of abuse, is associated with a
      significant number of Emergency Department (ED) visits. Methamphetamine use may
      produce psychiatric symptoms including acute psychosis, depression, and anxiety
      disorders. STUDY OBJECTIVES: To characterize psychiatric emergencies either
      directly or indirectly attributable to methamphetamine use in an urban academic
      ED. METHODS: We analyzed a database of patients determined to have an ED visit
      that was either methamphetamine related or non-methamphetamine related. We
      retrospectively reviewed the records of the subset of ED visits from this
      database with psychiatric diagnoses. We compared the characteristics of patients
      with methamphetamine-related psychiatric visits (MRPVs) and non-methamphetamine
      related psychiatric visits (non-MRPVs). RESULTS: We identified 130 patients with
      MRPVs. This represented 7.6% (130 of 1709) of all psychiatric visits. Patients
      with MRPV, compared to non-MRPV patients, were younger (34.4 years vs. 39.1
      years, respectively, p = 0.0005), more likely to be uninsured (55% vs. 37%,
      respectively, p = 0.001), and less likely to have a past history of depression
      (10% vs. 19%, respectively, p = 0.011). Many characteristics between the two
      groups (MRPV vs. non-MRPV) were similar: likelihood of patient being placed on a
      psychiatric hold; hospital charges; previous histories of psychiatric visits; and
      history of anxiety, bipolar disorder, or schizophrenia. CONCLUSIONS:
      Methamphetamine may be related to a significant proportion (7.6%) of psychiatric
      ED visits. Furthermore, patients with methamphetamine-associated psychiatric
      visits are younger, have lower rates of depression, are more likely to be
      uninsured, and are less likely to have a substance abuse-related chief complaint
      than patients with non-methamphetamine-associated ED psychiatric visits.

PMID- 23561311
TI  - The limited utility of screening laboratory tests and electrocardiograms in the
      management of unintentional asymptomatic pediatric ingestions.
AB  - BACKGROUND: Suspected ingestions are a common chief complaint to the emergency
      department although the majority of ingestions by children are insignificant.
      OBJECTIVE: Assess the utility of screening laboratory tests and
      Electrocardiograms (ECGs) in unintentional asymptomatic pediatric poisonings.
      METHODS: Retrospective chart review at a tertiary care children's hospital and a
      regional poison center of patients less than 12 years of age using ICD-9 codes
      from January 2005 through December 2008. Laboratory or ECG results requiring
      intervention and/or direct treatment, a non-RPC subspecialty consultation, and/or
      prolonged Emergency Department stay was considered changed management. RESULTS:
      Five hundred ninety five suspected ingestions met our criteria. The median age
      was 2.6 years (IQR 1.6, 3.0 years) and 56% were male. One laboratory test or ECG
      was obtained in 233 patients (39%). Of 24 screening ECGs, 32 complete blood
      counts and 34 blood gases, none were clinically significant. Fifty-two patients
      received screening metabolic panels, 3 were abnormal and 2 changed management
      (anion gap metabolic acidosis with unsuspected salicylate ingestions). None of
      the 127 (21%) screening acetaminophen levels changed management. Two of sixty
      five (13%) screening salicylate levels changed management. Three screening urine
      toxicology tests on patients with altered mental status were positive without
      ingestion history. No patient under the age of 12 years with normal vital signs
      and normal mental status had positive screening tests. CONCLUSIONS: Screening
      laboratory tests and ECGs were of limited utility and rarely changed management
      despite being ordered in a significant number of patients. Screening tests are
      rarely indicated in unintentional overdoses in children who are asymptomatic.

PMID- 23561312
TI  - Pediatric preparedness of Lebanese emergency departments.
AB  - BACKGROUND: The pediatric preparedness of Lebanese Emergency Departments (EDs)
      has not been evaluated. STUDY OBJECTIVES: To describe the number, regional
      location, and characteristics of EDs in Lebanon providing care to children and to
      describe the staffing, equipment, and support services of these EDs. METHODS: We
      surveyed hospitals in Lebanon caring for children in an ED setting between
      September 2009 and September 2010. The survey was provided in English and Arabic
      and could be completed in person, by telephone, or on the Web. RESULTS: We
      identified 115 EDs that cared for children in Lebanon; 72 (63%) completed the
      survey, most of which were urban (54%). Ninety-three percent of the EDs had
      <20,000 total patient visits annually; children (variably defined) accounted for
      <29% of the patients at 89% of the sites. Physicians caring for children in the
      EDs had varied medical training; and a pediatrician was "usually involved" in the
      management of pediatric patients in 95% of the EDs. Only 27% of EDs had attending
      physicians present 24 h/day to care for children. Half of the hospitals had an
      intensive care unit that could care for children (48%). Most EDs had endotracheal
      tubes (95%) and intravenous catheters (90%) in all pediatric sizes. CONCLUSION:
      The emergency care of children in Lebanon is provided at numerous hospitals
      throughout the country, with a wide range of staffing patterns and available
      support services.

PMID- 23561313
TI  - ''Rectal intussusception'': avoid the confusion.

PMID- 23561314
TI  - Acute subdural hematoma without subarachnoid hemorrhage or intraparenchymal
      hematoma caused by rupture of a posterior communicating artery aneurysm: case
      report and review of the literature.
AB  - BACKGROUND: Acute subdural hematoma without subarachnoid hemorrhage or
      intraparenchymal hematoma is rare. CASE REPORT: We report on a 47-year-old women
      without previous trauma who presented with an acute subdural hematoma without
      subarachnoid hemorrhage. The hematoma was evacuated immediately. Further
      evaluation with a cerebral four-vessel angiography revealed a left-sided
      posterior communicating artery aneurysm that was occluded by endovascular
      embolization. The patient recovered without neurological deficit. CONCLUSIONS:
      Ruptured intracranial aneurysm should be considered as a cause of nontraumatic
      subdural hematoma. Immediate subdural hematoma removal after aneurysm coiling can
      be performed in such patients, even those in poor neurological condition.

PMID- 23561315
TI  - Blood transfusion in deceased donor kidney transplantation.
AB  - BACKGROUND: Given the unpredictable timing of deceased donor organs and the need
      for blood transfusion, this study was carried out to determine the rate and risk
      factors for transfusion in order to identifying a low-risk cohort in the face of
      a critical blood shortage. METHODS: This retrospective chart review examined 306
      consecutive deceased solitary kidney transplant recipients from January 2006 to
      August 2012. RESULTS: Records show that 80 (26.1%) patients were transfused with
      a total of 300 units (0.98 units/transplant) during their first hospital stay.
      Transfusions were higher in patients on warfarin (8/14, 57%, 5.1
      units/transplant) and antiplatelet agents (46/136, 33.8%, 1.1 unit/transplant)
      compared to no anticoagulants (74/156, 16.7%, 0.47 units/transplant). In a
      multivariable logistic regression analysis warfarin (odd ratio (OR) 8.2, 95%
      confidence interval (CI) 2.5-27, P=0.001), antiplatelet agents (OR 2.9, 95% CI
      1.6-5.3, P=0.001), recipient age >=55 years (OR 2.2, 95% CI 1.2-3.9, P=0.008),
      recipient male (OR 0.36, 95% CI 0.2-0.64, P=0.001) and preop hemoglobin >=115 g/L
      (OR 0.32, 95% CI 0.18-0.57, P<0.001) were independent predictors of blood
      transfusion. Lower bleeding cohorts with transfusion rates <5% could not be
      identified. CONCLUSION: The need for blood is significantly higher in subjects on
      either warfarin or antiplatelet agents. These patients might be avoided if kidney
      transplantation is to occur during a critical blood shortage. Unfortunately even
      patients not on anticoagulation are at some risk.

PMID- 23561316
TI  - Hydrophobicity of imidazole derivatives correlates with improved activity against
      human methanogenic archaea.
AB  - Methanogenic archaea are involved in periodontitis in humans. They have also been
      implicated in digestive tract pathologies and obesity. These microorganisms are
      broadly resistant to antibiotics, except for metronidazole and ornidazole. In
      this study, eight imidazole derivatives were synthesised and their in vitro
      cytotoxicity and activity against six species of methanogenic archaea, including
      Methanobrevibacter smithii, Methanobrevibacter oralis, Methanosphaera stadtmanae,
      Methanobacterium beijingense, Methanosaeta concilii and Methanomassiliicoccus
      luminyensis, were tested. Whilst the effective half-maximum cytotoxic
      concentrations (EC50 values) of all compounds were <=50 mg/L, minimum inhibitory
      concentrations (MICs) were 0.05-0.8 mg/L for most methanogenic archaea and 0.1
      1mg/L for M. stadtmanae. These results indicated a >20-400 therapeutic index
      (EC50/MIC) for these compounds, which compared with metronidazole exhibited 1-log
      increased activity against methanogenic archaea cultured from the human
      microbiota. These compounds are therefore promising molecules for the treatment
      of methanogenic archaea-related infections.

PMID- 23561318
TI  - Gazing into the crystal ball: future considerations for ensuring sustained growth
      of the functional food and nutraceutical marketplace.
AB  - Over the last decade the concept of functional foods and nutraceuticals (FFN) has
      gained support from various stakeholders including the food industry, scientific
      and academic community, government institutions or regulators, producers and
      consumers. However, as one begins to evaluate the global FFN industry, several
      issues emerge including (i) a lack of consensus across jurisdictions for
      acknowledging safe and efficacious FFN, (ii) challenges regarding the
      classification of novel food-derived bioactives as FFN or drugs, and (iii) a
      disconnect between nutrient requirements and dosages of FFN required to
      facilitate health benefits. The objectives of the present review are to discuss
      the role of existing stakeholders within the FFN marketplace and identify
      performance indicators for growth within the FFN sector. In addition, the
      following report provides feasible resolutions to present and future challenges
      facing the global FFN industry to ensure sustained long-term growth.

PMID- 23561317
TI  - Non-battle craniomaxillofacial injuries from U.S. military operations.
AB  - INTRODUCTION: Non-battle injuries (NBIs) can be a source of significant resource
      utilization for the armed forces in a deployed setting. While the incidence and
      severity of craniomaxillofacial (CMF) battle injuries (BIs) have reportedly
      increased in the ongoing U.S. military conflicts in Iraq and Afghanistan, the
      prevalence and the nature of NBIs are not well described. MATERIAL AND METHODS:
      The Joint Theater Trauma Registry was queried from October 2001 to February 2011,
      covering Operations Enduring Freedom and Iraqi Freedom, for both NBIs and BIs to
      the CMF region. Patient demographics, injury severity score, mechanism and type
      of injury were included in the query. Using ICD-9 diagnosis codes, CMF injuries
      were classified according to type (wounds, fractures, burns, vascular injuries,
      and nerve injuries). Statistical analysis was performed for comparative analysis.
      RESULTS: NBIs constituted 24.3% of all patients with CMF injuries evacuated to a
      regional combat support hospital (CMF BIs 75.4%). These injuries were
      characterized by blunt trauma, most commonly motor vehicle collisions (37%), and
      falls (20%). As compared to CMF BIs, CMF NBIs resulted in less mortality (1.3%
      vs. 3.1%, p < 0.0001), fewer injuries per patient (1.87 vs. 2.26, p = 0.055), and
      a decreased severity score (ISS) (8.38 vs. 12.98, p < 0.0001). However, a
      significant percentage of CMF NBIs still required evacuation out of theater
      (27.8% of NBIs vs. 42.2% of BIs, p < 0.0001), depleting the combat strength of
      the deployed forces. CONCLUSIONS: CMF NBIs accounted for a substantial portion of
      total CMF injuries. Though characterized predominantly by blunt trauma with an
      overall better prognosis, its burden to the limited resources of a deployment can
      be significant. This descriptive study highlights the need to allocate
      appropriate resources for treatment of these injuries as well as strategies to
      reduce both its incidence and severity. LEVEL OF EVIDENCE: IV Prognostic.

PMID- 23561319
TI  - Tenidap, an agonist of the inwardly rectifying K+ channel Kir2.3, delays the
      onset of cortical epileptiform activity in a model of chronic temporal lobe
      epilepsy.
AB  - OBJECTIVE: Inwardly rectifying K(+) (Kir) channel, Kir2.3, has been found down
      regulated in the hippocampus of chronic temporal lobe epileptic (cTLE) patients
      which may underline the mechanism of epilepsy. Tenidap is an agonist of Kir2.3.
      However, the effect of tenidap on cTLE remains obscure. The aim of the present
      study was to observe the relationship between Kir2.3 and the pathogenesis of
      cTLE, and to explore the potential effect of Kir agonists as anti-epileptic
      drugs. METHODS: The pilocarpine temporal lobe epilepsy (TLE) rat model was
      established and status epilepticus (SE) was induced in rats. The rats were
      divided into four groups based on time points (0 hours, 6 hours, 72 hours, and
      two weeks) after SE termination. The dynamic changes in Kir2.3 mRNA and protein
      expression in the hippocampus were detected at each time point by reverse
      transcription polymerase chain reaction (RT-PCR) and western blotting to
      determine an appropriate time for further intervention and observation. Then,
      tenidap was administered and its effect on the expression of Kir2.3 mRNA/protein
      and the electroencephalogram (EEG) wave was documented at predetermined time
      points. RESULTS: The pattern of Kir2.3 mRNA and protein expression was bimodal,
      as it increased immediately after SE and declined at two weeks, when compared
      with the control group. Down-regulation of the Kir channels may lead to an
      impaired clearance of K(+) ions from the extracellular space and result in a
      stronger neuronal depolarisation. Two weeks after SE may be a reversal point.
      Spontaneous recurrent seizures (SRS) appeared at the two-week point, indicating
      that chronic epilepsy had occurred. Tenidap up-regulated expressions of both
      Kir2.3 channel mRNA and protein, which may help to maintain the resting membrane
      potential (RMP) and hyperpolarisation of the cells. CONCLUSIONS: Our results
      suggest that the down-regulation of the Kir2.3 channel expression might
      contribute to the pathogenesis of TLE, which may be ameliorated by the
      administration of tenidap.

PMID- 23561320
TI  - Cardiac papillary fibroelastoma: a retrospect of four cases.
AB  - OBJECTIVE: We have reviewed the medical histories of 4 patients who underwent
      operations between November 2004 and February 2011 at Changhai Hospital for
      cardiac papillary fibroelastoma. METHODS: Diagnosis was demonstrably suggested by
      echocardiography. Tumor locations were mitral valve (1), left atrium (1), and
      aortic valve (2). Indications for operation were previous cerebrovascular
      accident for the mitral tumor, incidental apopsychia and giant mobile mass for
      the left atrium, ingravescent chest tightness and palpitations for the first
      aortic tumor, and severe regurgitation of aortic valve for the second aortic
      tumor. The study was approved by the Changhai Hospital Ethics Committee, and the
      consent from the patients or their immediate family was obtained. RESULTS:
      Surgical excision with necessary valve replacement operations was performed in
      all cases. All patients had uneventful postoperative recoveries. No evidence of
      regurgitation or recurrence was seen on echocardiography at follow-up.
      CONCLUSIONS: Despite their histologically benign aspect, cardiac papillary
      fibroelastomas should be removed because of potential embolic complications.

PMID- 23561321
TI  - Is sexual selection defined by dimorphism alone? A reply to Padian and Horner.

PMID- 23561322
TI  - How does pedogenesis drive plant diversity?
AB  - Some of the most species-rich plant communities occur on ancient, strongly
      weathered soils, whereas those on recently developed soils tend to be less
      diverse. Mechanisms underlying this well-known pattern, however, remain
      unresolved. Here, we present a conceptual model describing alternative mechanisms
      by which pedogenesis (the process of soil formation) might drive plant diversity.
      We suggest that long-term soil chronosequences offer great, yet largely untapped,
      potential as 'natural experiments' to determine edaphic controls over plant
      diversity. Finally, we discuss how our conceptual model can be evaluated
      quantitatively using structural equation modeling to advance multivariate
      theories about the determinants of local plant diversity. This should help us to
      understand broader-scale diversity patterns, such as the latitudinal gradient of
      plant diversity.

PMID- 23561323
TI  - Simulated biomechanical responses at a curved arterial segment after Wingspan
      Stent deployment in swine.
AB  - OBJECTIVES: Endovascular treatment with the Wingspan Stent is frequently
      associated with in-stent restenosis at the curved portion, leading to late-phase
      stroke. To explore the cause of stroke complications after treatment with the
      Wingspan Stent, we simulated the biomechanical responses at a curved arterial
      segment using the finite element method. METHODS: A Wingspan stent was deployed
      at a slightly curved ascending pharyngeal artery (APA) in swine. Several stress
      distributions modeling solid mechanics were analyzed with structural deformation.
      Histopathological analysis of the selected APA was assessed at 28 days after
      stenting. RESULTS: Arterial straightening was simulated in this study. Both
      radial stress (RS) and circumferential stress (CS) concentrations increased at
      both stent ends. Marked lower axial stress (AS) concentration was observed at the
      outer wall of an arterial curvature. The proximal stent segment, ending in the
      curved portion, significantly impacted the solid mechanical environment.
      Eccentric neointimal hyperplasia was observed at the curved segment. DISCUSSION:
      These results show that the Wingspan stent exaggerated the non-uniform stress
      distributions in a curved artery. The understanding of stent-arterial wall
      interactions is of value to identify the current limitations of intracranial
      stenting, and will help to improve this treatment methodology and future devices.

PMID- 23561324
TI  - Integration of halofuginone lactate treatment and disinfection with p-chloro-m
      cresol to control natural cryptosporidiosis in calves.
AB  - Two field studies were accomplished on a dairy farm in Saxony to compare
      different strategies for the control of natural cryptosporidiosis in newborn
      calves. In the first study, 96 newborn calves were allocated to four different
      groups immediately after birth. Calves of group H and of group HN were treated
      orally with 120 MUg/kg body weight (BW) of halofuginone lactate daily during the
      first seven days of life. Calves of group C and of group CN were treated with a
      same volume of tap water. As an additional measure, the pens of groups HN and CN
      were disinfected with 3% Neopredisan 135-1((r))(p-chloro-m-cresol), the pens of
      groups C and H remained non-disinfected. Faeces were examined semi-quantitatively
      for oocyst excretion using carbolfuchsin-staining and the clinical course was
      recorded. While disinfection alone (group CN) had no effect on oocyst shedding
      and diarrhoea, treatment with halofuginone lactate (groups H and HN) reduced
      oocyst shedding and diarrhoea significantly. Combination of treatment and
      disinfection (group HN) controlled cryptosporidiosis completely during the first
      two weeks after birth. However, prevalence of diarrhoea and oocyst shedding was
      higher in the third week of life in group HN than in any of the other groups.
      This delayed occurrence of cryptosporidiosis was not seen in study 2 when all
      calves were similarly protected by treatment and specific disinfection. Oocyst
      shedding was not observed in peripartal cows either by carbolfuchsin staining,
      ELISA or PCR.

PMID- 23561325
TI  - A systematic review and meta-analysis of the factors associated with Leishmania
      infantum infection in dogs in Brazil.
AB  - The risk factors associated with canine visceral leishmaniosis (CVL) in Brazil
      are unclear and controversial. The objectives of this systematic review and meta
      analysis were to identify the best evidence available in this field and to
      determine the gaps in existing knowledge. Literature searches were carried out
      using four databases, the reference lists within articles, and references
      provided by experts in the field. Theoretical discussions or separate and
      independent meta-analyses of p-values or of effect sizes were used to pool
      information about each variable. Thirty-six articles were selected for detailed
      review, including 31 cross-sectional, two ecological and three cohort studies.
      The variables showing significant association with CVL were short hair, purebred,
      peri-domestic restricted (as compared with domestic-restricted dogs), and
      presence of green areas adjacent to home. The occurrence of CVL was also
      associated with the presence of domestic fowl in the home environment, with free
      dogs (as compared with restrained dogs), with male gender and with dogs >1 or 2
      years of age, although these associations were not statistically significant. Due
      to the small number of publications, consistent results could not be obtained
      concerning the role of other factors. Most studies did not describe the criteria
      of eligibility and the process of selection of participants in sufficient detail
      and employed only one diagnostic test as proof of infection. Few studies
      controlled for confounding variables. No statistical evidence of publication bias
      was detected, but a great deal of information contained in the primary articles
      was lost because the results were not adequately described. The results of this
      review contribute to a better understanding of CVL and should assist in
      optimizing the development and implementation of control policies. Continuous
      actions, prioritizing dogs at higher risk and areas with higher abundance of
      green vegetation, together with policies to promote responsible dog ownership are
      mandatory. Problems concerning study design and data analysis described in the
      present study need to be taken into consideration in future studies. These must
      follow clear procedures to select participants and utilize standardized, valid
      and reliable diagnostic methods. The development of multivariate models and the
      use of the STROBE statement for description of the results should also be
      encouraged. Further research should investigate the patterns identified and
      prioritize CVL-related factors that have not been fully recognized or elucidated.
      Finally, ecological and cohort studies of CVL and investigations in other
      countries of Latin America are urgently required.

PMID- 23561326
TI  - Neuromodulatory effect of progesterone on the dopaminergic, glutamatergic, and
      GABAergic activities in a male rat model of Parkinson's disease.
AB  - OBJECTIVES: Progesterone has been reported to have a neuroprotective role in
      depression-like rats in a hemiparkinsonian model of the disease. In this work, we
      investigate if this hormone affects the three principal neurochemicals striatal
      systems (dopaminergic, glutamatergic, and GABAergic) that are involved in the
      physiopathology of the disease in a hemiparkinsonim male rat model at 8 weeks
      post-chemical injury. METHODS: For this purpose, we design three experimental
      groups: (1) sham group; (2) hemiparkinsonian group; and (3) hemiparkinsonian
      group subcutaneously injected with progesterone at 7 days post-chemical injury.
      Animals were tested in an automated rotational device at 8 weeks post-chemical
      injury. After behavioral test, K(+)-evoked [(3)H]-dopamine, [(3)H]-glutamate, and
      [(3)H]-gamma aminobutyric acid release from striatum slices were analyzed by
      superfusion experiments. RESULTS: The hemiparkinsonian group showed distinctive
      alterations that are produced by neurodegeneration of left nigrostriatal
      dopaminergic pathway by 6-hydroxydopamine hydrobromide (6-OHDA). On the other
      hand, the administration of progesterone 7 days after the injection of the
      neurotoxin was able to (1) improve the K(+)-evoked [(3)H]-dopamine release from
      the damaged striata (left); (2) avoid significant increase in the K(+)-evoked
      [(3)H]-glutamate release from the left striata; and (3) progesterone does not
      modify the K(+)-evoked [(3)H]-gamma aminobutyric acid release from the left
      striata. DISCUSSION: These results suggest that progesterone does have
      neuroprotective and neuromodulatory effects on striatal neurotransmission systems
      in the hemiparkinsonian male rats. The possible mechanisms would involve genomic
      and non-genomic actions of this neuroactive steroid which would modulate the
      activity of dopaminergic, glutamatergic, and GABAergic pathways.

PMID- 23561328
TI  - Effects of different sleeping postures on intraocular pressure and ocular
      perfusion pressure in healthy young subjects.
AB  - OBJECTIVE: To investigate the effects of different sleeping positions of head and
      body on intraocular pressure (IOP) and ocular perfusion pressure (OPP) in
      healthy, young subjects. DESIGN: Prospective, comparative case series.
      PARTICIPANTS: Twenty healthy young Korean subjects. METHODS: We measured IOP and
      blood pressure (BP) with the subjects seated and recumbent, including supine,
      right lateral decubitus, left lateral decubitus, prone with right head turn, and
      prone with left head turn positions. We measured IOP using an Icare tonometer in
      both eyes 5 minutes after assuming each position in a randomized sequence. We
      calculated the OPP using the formulas based on the mean BP adjusted for the
      height of the eye over the heart. The eye on the lower side in the lateral
      decubitus or prone with head turn position was termed the dependent eye. MAIN
      OUTCOME MEASURES: Difference in IOP and OPP of the dependent and nondependent
      eyes during changes of sleeping positions of body and head. RESULTS: Mean IOP of
      right and left eyes while sitting was significantly lower than that measured in
      each recumbent position (all P<0.001). The OPPs in both eyes were significantly
      higher in all recumbent positions than in a sitting position (all P<0.001). Mean
      IOP of the dependent eyes was higher than that of the nondependent eyes in the
      lateral decubitus positions and in the prone positions with head turns (all
      P<0.001). No significant intereye difference in OPP was found for any position.
      Among IOPs measured in the recumbent positions, mean IOP of the dependent eye in
      the lateral decubitus position or in the prone position with head turn was
      significantly higher than that of the ipsilateral eye in the supine position (all
      P<0.0001). CONCLUSIONS: All sleeping positions of head and body resulted in an
      elevation of IOP and an increase in the calculated OPP compared with the sitting
      position in healthy, young subjects. The postural change from supine to lateral
      decubitus or prone with head turn position increased the IOP of the dependent
      eyes without significant alteration in OPP in healthy awake subjects. Further
      research is needed under nocturnal conditions in a sleep laboratory. FINANCIAL
      DISCLOSURES: The authors have no proprietary or commercial interest in any of the
      materials discussed in this article.

PMID- 23561327
TI  - Prevalence and causes of visual impairment in Asian and non-Hispanic white
      preschool children: Multi-ethnic Pediatric Eye Disease Study.
AB  - PURPOSE: To determine the prevalence and causes of decreased visual acuity (VA).
      DESIGN: Population-based cross-sectional study. PARTICIPANTS: Multi-ethnic sample
      of children 30 to 72 months of age identified in Los Angeles. METHODS: All
      eligible children underwent a comprehensive ophthalmic evaluation including
      monocular VA testing, cover testing, cycloplegic autorefraction, fundus
      evaluation, and VA retesting with refractive correction. Decreased VA was defined
      as presenting or best-measured VA worse than 20/50 in children 30 to 47 months of
      age and worse than 20/40 for children 48 months of age and older. The prevalence
      and causes of decreased VA were determined, for both presenting and best-measured
      VA, in the better-seeing and the worse-seeing eyes. MAIN OUTCOME MEASURES:
      Prevalence and causes of decreased vision. RESULTS: Presenting VA was assessed in
      1840 children and best-measured VA was assessed in 1886 children. Presenting VA
      was decreased in the worse eye of 4.2% of Asian children and of 3.6% of non
      Hispanic white (NHW) children. Close to one-fourth of these cases had no
      identifiable cause, and 81% of these resolved on retesting. Decreased presenting
      VA in the worse eye with an identifiable ophthalmic cause was present in 3.4% of
      Asian children and in 2.6% of NHW children. Decreased presenting VA attributable
      to simple refractive error (myopia >= 0.5 diopters [D]; hyperopia >= 3.0 D;
      astigmatism >= 2.0 D or >= 1.5 D for children older than 36 months) was present
      in the worse eye of 2.3% of Asian children and of 1.4% of NHW children and in the
      better eye of 0.5% of Asian children and of 0.3% of NHW children. Decreased best
      measured VA attributable to a cause was present in the worse eye of 1.2% of both
      Asian children and NHW children and in the better eye of 0.2% of Asian and of
      0.3% of NHW children. Amblyopia related to refractive error was the most common
      cause, and was 10 times as common as ocular disease. Severe visual impairment was
      rare. CONCLUSIONS: Seventy percent of all decreased VA in Asian and NHW preschool
      children and more than 90% of decreased VA with an identifiable cause is related
      to refractive error--either uncorrected refractive error or amblyopia resulting
      from refractive error. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 23561329
TI  - IL-6 expression predicts treatment response and outcome in squamous cell
      carcinoma of the esophagus.
AB  - BACKGROUND: The identification of potential tumor markers can improve therapeutic
      planning and patient management. The aim of this study was to highlight the
      significance of IL-6 in esophageal squamous cell carcinoma (SCC). METHODS: We
      retrospectively analyzed the clinical outcomes of 173 patients with esophageal
      SCC, and examined the correlation between IL-6 levels and clinical outcomes in
      esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T
      was selected for cellular and animal experiments to investigate changes in tumor
      behavior and treatment response after manipulation of IL-6 expression. RESULTS:
      In clinical outcome analysis, positive IL-6 staining and poor treatment response
      was significantly associated with shorter survival. Furthermore, the frequency of
      IL-6 immunoreactivity was significantly higher in esophageal cancer specimens
      than in non-malignant epithelium, and this staining was positively linked to the
      development of distant metastasis (p = 0.0003) and lower treatment response rates
      (p = 0.0001).By ELISA analysis, IL-6 serum levels were significantly elevated in
      patients developing disease failure.When IL-6 expression was inhibited,
      aggressive tumor behavior and radiation resistance could be overcome in vitro and
      in vivo. The underlying changes included increased cell death, less epithelial
      mesenchymal transition and attenuated STAT3 activation. IL-6 inhibition was also
      associated with attenuated angiogenesis in tumor-bearing mice. CONCLUSIONS: IL-6
      was significantly associated with poor prognosis in patients with esophageal
      cancer. Targeting this cytokine could be a promising strategy for treatment of
      esophageal cancer, as evidenced by inhibition of aggressive tumor behavior and
      treatment resistance.

PMID- 23561330
TI  - Serum lipid-improving effect of soyabean beta-conglycinin in hyperlipidaemic
      menopausal women.
AB  - To evaluate the effect of treatment with beta-conglycinin, a major soyabean
      protein, on blood lipids in menopausal women, we recruited 100 hyperlipidaemic
      women aged 40-60 years old. Participants were randomly allocated to three groups:
      placebo group (n 34, four casein tablets/d); low dose group (n 33, four tablets
      containing 2.3 g beta-conglycinin/d); high-dose group (n 33, eight tablets
      containing 4.6 g beta-conglycinin/d). The mean serum TAG concentration was
      significantly reduced after 6 and 12 weeks of beta-conglycinin intervention by
      0.44 (sd 0.20) and 0.78 (sd 1.03) mmol/l in the low-dose group, and by 0.46 (sd
      0.17) and 1.25 (sd 1.06) mmol/l in the high-dose group, respectively. One-way
      ANOVA revealed that serum TAG concentrations in the low-dose and high-dose groups
      were significantly lowered compared with the placebo group at weeks 6 and 12 (P<
      0.05). The low dose and high dose consumptions of beta-conglycinin significantly
      decreased the LDL-cholesterol concentration by 0.46 (sd 0.72) and 0.52 (sd 0.97)
      mmol/l at week 12, respectively (P< 0.05). Compared with the changes from
      baseline in the placebo group, apoB and NEFA were significantly lowered in both
      the low-dose and high-dose beta-conglycinin groups (P< 0.05). In conclusion, the
      results suggest that beta-conglycinin intake significantly decreases serum TAG
      and LDL-cholesterol levels.

PMID- 23561332
TI  - Selenium inhibits the phytotoxicity of mercury in garlic (Allium sativum).
AB  - To investigate the influence of selenium on mercury phytotoxicity, the levels of
      selenium and mercury were analyzed with inductively coupled plasma-mass
      spectrometry (ICP-MS) in garlic tissues upon exposure to different dosages of
      inorganic mercury (Hg(2+)) and selenite (SeO3(2-)) or selenate (SeO4(2-)). The
      distributions of selenium and mercury were examined with micro-synchrotron
      radiation X-ray fluorescence (MU-SRXRF), and the mercury speciation was
      investigated with micro-X-ray absorption near edge structure (MU-XANES). The
      results show that Se at higher exposure levels (>1mg/L of SeO3(2-) or SeO4(2-))
      would significantly inhibit the absorption and transportation of Hg when Hg(2+)
      levels are higher than 1mg/L in culture media. SeO3(2-) and SeO4(2-) were found
      to be equally effective in reducing Hg accumulation in garlic. The inhibition of
      Hg uptake by Se correlates well with the influence of Se on Hg phytotoxicity as
      indicated by the growth inhibition factor. Elemental imaging using MU-SRXRF also
      shows that Se could inhibit the accumulation and translocation of Hg in garlic.
      MU-XANES analysis shows that Hg is mainly present in the forms of Hg-S bonding as
      Hg(GSH)2 and Hg(Met)2. Se exposure elicited decrease of Hg-S bonding in the form
      of Hg(GSH)2, together with Se-mediated alteration of Hg absorption,
      transportation and accumulation, may account for attenuated Hg phytotoxicity by
      Se in garlic. 

PMID- 23561331
TI  - Factors in sustained recovery from cocaine dependence.
AB  - The goal was to identify factors that predicted sustained cocaine abstinence and
      transitions from cocaine use to abstinence over 24 months. Data from baseline
      assessments and multiple follow-ups were obtained from three studies of
      continuing care for patients in intensive outpatient programs (IOPs). In the
      combined sample, remaining cocaine abstinent and transitioning into abstinence at
      the next follow-up were predicted by older age, less education, and less cocaine
      and alcohol use at baseline, and by higher self-efficacy, commitment to
      abstinence, better social support, lower depression, and lower scores on other
      problem severity measures assessed during the follow-up. In addition, higher self
      help participation, self-help beliefs, readiness to change, and coping assessed
      during the follow-up predicted transitions from cocaine use to abstinence. These
      results were stable over 24 months. Commitment to abstinence, self-help behaviors
      and beliefs, and self-efficacy contributed independently to the prediction of
      cocaine use transitions. Implications for treatment are discussed.

PMID- 23561333
TI  - A model of study for human cancer: Spontaneous occurring tumors in dogs.
      Biological features and translation for new anticancer therapies.
AB  - Murine cancer models have been extremely useful for analyzing the biology of
      pathways involved in cancer initiation, promotion, and progression.
      Interestingly, several murine cancer models also exhibit heterogeneity, genomic
      instability and an intact immune system. However, they do not adequately
      represent several features that define cancer in humans, including long periods
      of latency, the complex biology of cancer recurrence and metastasis and outcomes
      to novel therapies. Therefore, additional models that better investigate the
      human disease are needed. In the pet population, with special references to the
      dog, cancer is a spontaneous disease and dogs naturally develop cancers that
      share many characteristics with human malignancies. More than 40 years ago,
      optimization of bone marrow transplantation protocols was undertaken in dogs and
      recently novel targeted therapies such as liposomal muramyl tripeptide
      phosphatidylethanolamine and several tyrosine kinase inhibitors, namely masitinib
      (AB1010) and toceranib phosphate (SU11654), have been developed to treat dog
      tumors which have then been translated to human clinical trials. In this review
      article, we will analyze biological data from dog tumors and comparative features
      with human tumors, and new therapeutic approaches translated from dog to human
      cancer. 

PMID- 23561334
TI  - Anti-thymocyte globulins for post-transplant graft-versus-host disease
      prophylaxis-A systematic review and meta-analysis.
AB  - BACKGROUND: Despite advances made in allogeneic hematopoietic stem cell
      transplantation (alloSCT), graft versus host disease (GvHD) remains a major
      problem. The main strategy to combat GvHD is prophylaxis and ATG plays a major
      role in this arena. Conflicting reports on the effectiveness of ATG on GvHD
      prevention prompted us to address this question by means of a systematic review
      and meta-analysis. METHODS: Six prospective randomized controlled trials (RCT)
      comparing the addition of ATG to standard immunosuppressive regimen as GvHD
      prophylaxis were analyzed. All ATG preparations were considered but homogeneity
      in type of preparation and dosage had to be observed within each trial. RESULTS:
      Our meta-analysis reveals that the incidence of grade II-IV GvHD was
      significantly lower in patients receiving ATG. Addition of ATG had no impact on
      overall survival, relapse or non-relapse mortality. CONCLUSIONS: Based on the
      current level of the data analyzed in this systematic review, we cannot conclude
      a general recommendation for the use of ATG for GvHD prophylaxis in alloSCT. In
      patients who are at high risk for severe GvHD it should be considered
      individually. However, due to the heterogeneity of the analyzable studies it
      seems likely that future studies might change the results of the pooled data of
      this meta-analysis. In order to improve the current level of data, further
      randomized studies in this topic are therefore urgently warranted.

PMID- 23561336
TI  - Re: perioperative outcomes of robotic-assisted partial nephrectomy in elderly
      patients: a matched-cohort study.

PMID- 23561337
TI  - Re: outcomes of laparoscopic and robotic radical cystectomy in the elderly
      patients.

PMID- 23561338
TI  - Re: live robotic surgery: are outcomes compromised?

PMID- 23561339
TI  - Re: population-based comparative effectiveness of nephron-sparing surgery vs
      ablation for small renal masses.

PMID- 23561340
TI  - Re: a phase 2 cancer chemoprevention biomarker trial of isoflavone g-2535
      (genistein) in presurgical bladder cancer patients.

PMID- 23561341
TI  - Re: metabolomics study on the biochemical profiles of odor elements in urine of
      human with bladder cancer.

PMID- 23561342
TI  - Re: an updated prostate cancer staging nomogram (partin tables) based on cases
      from 2006 to 2011.

PMID- 23561343
TI  - Re: transition zone prostate cancer: detection and localization with 3-t
      multiparametric MR imaging.

PMID- 23561344
TI  - Re: active surveillance for low-risk prostate cancer worldwide: the PRIAS study.

PMID- 23561345
TI  - Re: multidisciplinary care and pursuit of active surveillance in low-risk
      prostate cancer.

PMID- 23561346
TI  - Re: significance of docetaxel-based chemotherapy as treatment for metastatic
      castration-resistant prostate cancer in Japanese men over 75 years old.

PMID- 23561347
TI  - Re: increased incidence of penile cancer and high-grade penile intraepithelial
      neoplasia in denmark 1978-2008: a nationwide population-based study.

PMID- 23561348
TI  - Re: lactobacilli vs antibiotics to prevent urinary tract infections: a
      randomized, double-blind, noninferiority trial in postmenopausal women.

PMID- 23561349
TI  - Re: predictive value of escherichia coli susceptibility in strains causing
      asymptomatic bacteriuria for women with recurrent symptomatic urinary tract
      infections receiving prophylaxis.

PMID- 23561350
TI  - Re: recurrent nephrolithiasis in adults: comparative effectiveness of preventive
      medical strategies [internet].

PMID- 23561352
TI  - Re: radiation dose reduction at multidetector CT with adaptive statistical
      iterative reconstruction for evaluation of urolithiasis: how low can we go?

PMID- 23561353
TI  - Re: abnormalities of 24-hour urine composition in first-time and recurrent stone
      formers.

PMID- 23561354
TI  - Re: eau guidelines on penile curvature.

PMID- 23561355
TI  - Re: simultaneous penile lengthening and penile prosthesis implantation in
      patients with peyronie's disease, refractory erectile dysfunction, and severe
      penile shortening.

PMID- 23561356
TI  - Re: does body mass index impact the performance of robot-assisted intracorporeal
      ileal conduit?

PMID- 23561358
TI  - Re: a midurethral sling to reduce incontinence after vaginal prolapse repair.

PMID- 23561360
TI  - Re: a randomized trial of urodynamic testing before stress-incontinence surgery.

PMID- 23561361
TI  - Re: monotherapy with tadalafil or tamsulosin similarly improved lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia in an international,
      randomised, parallel, placebo-controlled clinical trial.

PMID- 23561362
TI  - Re: finasteride adherence-associated factors in chinese benign prostatic
      hyperplasia patients.

PMID- 23561363
TI  - Re: prescriber monitoring for benign prostatic hyperplasia within a family
      medicine clinic: a comparison of medication classes.

PMID- 23561364
TI  - Re: sleep analysis of patients with nocturia and benign prostatic obstruction.

PMID- 23561365
TI  - Re: recovery of overall exercise ability, quality of life, and continence after
      12-week combined exercise intervention in elderly patients who underwent radical
      prostatectomy: a randomized controlled study.

PMID- 23561366
TI  - Re: pulsatile pump decreases risk of delayed graft function in kidneys donated
      after cardiac death.

PMID- 23561367
TI  - Re: long-term results of biopsy-guided selection and allocation of kidneys from
      older donors in older recipients.

PMID- 23561368
TI  - Re: kidney transplant ureteroneocystostomy: comparison of full-thickness vs. Lich
      Gregoir techniques.

PMID- 23561369
TI  - Re: evaluation of sexual function in sexually active women 1 year after
      transvaginal NOTES: a prospective cohort study of 106 patients.

PMID- 23561370
TI  - Re: quality of life among women with sexual dysfunction undergoing hemodialysis:
      a cross-sectional observational study.

PMID- 23561372
TI  - Re: prospective evaluation of patient satisfaction, and surgeon and patient
      trainer assessment of the coloplast titan one touch release three-piece
      inflatable penile prosthesis.

PMID- 23561373
TI  - Re: the prevalence of premature ejaculation and its clinical characteristics in
      korean men according to different definitions.

PMID- 23561375
TI  - Re: caucasian male infants and boys with hypospadias exhibit reduced anogenital
      distance.

PMID- 23561376
TI  - Re: genome-wide association study identifies candidate genes for male fertility
      traits in humans.

PMID- 23561377
TI  - Re: human sperm head vacuoles are physiological structures formed during the
      sperm development and maturation process.

PMID- 23561378
TI  - Re: recording and sorting live human sperm undergoing acrosome reaction.

PMID- 23561379
TI  - Re: sperm DNA fragmentation index does not correlate with the sperm or embryo
      aneuploidy rate in recurrent miscarriage or implantation failure patients.

PMID- 23561380
TI  - Re: health benefits in 2012: moderate premium increases for employer-sponsored
      plans; young adults gained coverage under ACA.

PMID- 23561381
TI  - Re: a simulation shows limited savings from meeting quality targets under the
      medicare shared savings program.

PMID- 23561382
TI  - Re: fee-for-service will remain a feature of major payment reforms, requiring
      more changes in medicare physician payment.

PMID- 23561383
TI  - Re: the new era of payment reform, spending targets, and cost containment in
      massachusetts: early lessons for the nation.

PMID- 23561384
TI  - Re: split dorsal dartos flap transposed ventrally as a bed for preputial skin
      graft in primary staged hypospadias repair.

PMID- 23561385
TI  - Re: neonatal circumcision reduces the incidence of asymptomatic urinary tract
      infection: a large prospective study with long-term follow up using Plastibell.

PMID- 23561386
TI  - Re: the risk of cryptorchidism among sons of women working in horticulture in
      denmark: a cohort study.

PMID- 23561387
TI  - Re: use of a vascularized tunica vaginalis flap for repair of testicular rupture
      in a pediatric patient.

PMID- 23561388
TI  - Re: effectiveness of a combination therapy using calcineurin inhibitor and mTOR
      inhibitor in preventing allograft rejection and post-transplantation renal cancer
      progression.

PMID- 23561389
TI  - Re: cancer stem-like cells contribute to Cisplatin resistance and progression in
      bladder cancer.

PMID- 23561390
TI  - Re: potential role of hsp90 inhibitors in overcoming Cisplatin resistance of
      bladder cancer-initiating cells.

PMID- 23561391
TI  - Re: loss of the urothelial differentiation marker FOXA1 is associated with high
      grade, late stage bladder cancer and increased tumor proliferation.

PMID- 23561393
TI  - Investigation of an angular spectrum approach for pulsed ultrasound fields.
AB  - An Angular Spectrum Approach (ASA) is formulated and employed to simulate linear
      pulsed ultrasound fields for high bandwidth signals. A geometrically focused
      piston transducer is used as the acoustic source. Signals are cross-correlated to
      find the true sound speed during the measurement to make the simulated and
      measured pulses in phase for comparisons. The calculated sound speed in the
      measurement is varied between 1487.45 m/s and 1487.75 m/s by using different
      initial values in the ASA simulation. Results from the pulsed ASA simulations
      using both Field II simulated and hydrophone measured acoustic sources are
      compared to the Field II simulated and hydrophone measured pulses, respectively.
      The total relative root mean square (RMS) errors of the pulsed ASA are
      investigated by using different time-point, zero-padding factors, spatial
      sampling interval and temporal sampling frequency in the simulation. Optimal
      parameters for the ASA are found in the simulation. The RMS error of the ASA
      simulation is reduced from 10.9% to 2.4% for the optimal parameters when
      comparing to Field II simulations. The comparison between the ASA calculated and
      measured pulses are illustrated and the corresponding RMS error is 25.4%.

PMID- 23561394
TI  - Temporally distinct cognitive effects following acute administration of ketamine
      and phencyclidine in the rat.
AB  - Non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as
      phencyclidine (PCP) and ketamine are commonly and interchangeably used to model
      aspects of schizophrenia in animals. We compared here the effects of acute
      administration of these compounds over a range of pre-treatment times in tests of
      instrumental responding (VI 30s response schedule), simple reaction time (SRT)
      and cognitive flexibility (reversal learning and attentional set shifting digging
      task) in rats. At standard pre-treatment times (15-30 min), both ketamine and PCP
      produced overall response suppression in VI 30 and increased reaction times in
      SRT suggesting that any concomitant cognitive performance deficits are likely to
      be confounded by motor and/or motivational changes. However, the use of extended
      pre-treatment times produced deficits in cognitive flexibility measured up to 4h
      after drug administration in the absence of motor/motivational impairment.
      Generally, PCP increased impulsive responding in the SRT indicating a possible
      loss of inhibitory response control that may have contributed to deficits
      observed in reversal learning and attentional set-shifting. In contrast to PCP,
      ketamine did not have the same effect on impulsive responding, and possibly as a
      consequence produced more subtle cognitive deficits in attentional set-shifting.
      In summary, acute treatment with NMDAR antagonists can produce cognitive deficits
      in rodents that are relevant to schizophrenia, provided that motor and/or
      motivational effects are allowed to dissipate. The use of longer pre-treatment
      times than commonly employed might be advantageous. Also, ketamine, which is more
      frequently used in clinical settings, did not produce as extensive cognitive
      deficits as PCP.

PMID- 23561395
TI  - The anti-idiotypic antibody 1F7 stimulates monocyte interleukin-10 production and
      induces endotoxin tolerance.
AB  - BACKGROUND: Pathogens that establish chronic infection elicit immune responses
      with suppressive cytokines dominating over pro-inflammatory cytokines. Chronic
      hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection
      and simian immunodeficiency virus (SIV) infection are associated with high levels
      of antiviral antibodies expressing a common idiotype specifically recognized by
      the 1F7 monoclonal antibody (mAb). The 1F7 mAb is a murine IgMkappa antibody
      raised against immunoglobulin pooled from the plasma of multiple HIV-infected
      individuals. In this study, we investigated direct effects of the 1F7 mAb itself
      on peripheral blood mononuclear cells (PBMC). METHODS: Isolated monocytes or PBMC
      from healthy controls were incubated with the 1F7 mAb or IgMkappa mAb control.
      Cytokine production was measured in cell culture supernatants by ELISA and cells
      producing interleukin-10 (IL-10) were identified by subset depletion and
      intracellular flow cytometry. Endotoxin tolerance was assessed by exposing
      monocytes to lipopolysaccharide (LPS) following 1F7 mAb or IgMkappa mAb control
      pre-treatment and comparing tumor necrosis factor (TNF)-alpha levels in cell
      culture supernatants. RESULTS: The 1F7 mAb stimulated monocytes and CD36+
      lymphocytes to produce IL-10 in a time and dose-dependent manner. Treatment of
      monocytes with 1F7 mAb also reduced their subsequent responsiveness to LPS
      stimulation. CONCLUSIONS: Induction of antibodies expressing the 1F7 idiotype by
      chronic pathogens may facilitate IL-10 production and progression to chronic
      infection. Direct effects of IL-10 from human monocytes stimulated by 1F7-like
      antibodies, followed by monocyte transition to an alternatively activated
      phenotype illustrated by endotoxin tolerance, are two complementary features
      favouring a tolerogenic or non-responsive immunological environment.

PMID- 23561396
TI  - Clinical outcome and quality of life after reoperative CABG: off-pump versus on
      pump - observational pilot study.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) on cardiopulmonary bypass
      (CBP) is associated with significant morbidity and mortality. In high-risk
      patients, doomed for reoperation the adverse effects of CBP may be more striking.
      We evaluated the results of reoperative CABG (redo-CABG) by either off-pump
      (OPCAB) or on-pump (ONCAB). Clinical endpoints were perioperative myocardial
      infarction, mortality, survival and as the most striking difference between prior
      studies the quality of life (QoL). METHODS: We performed a prospective, non
      randomized assessment for patients who underwent redo-CABG by redo-OPCAB (n=40)
      or redo-ONCAB (n=40) at our institution between January 2007 and December 2010.
      For evaluation of QoL the SF-36 health survey was used with self-administered
      assessment. RESULTS: During follow-up 37 of 40 patients were alive in the redo
      OPCAB group versus 32 of 40 patients in the redo-ONCAB group (p<0.05). The
      shorter operation time, less blood loss, fewer perioperative myocardial
      infarctions, the higher rate of totally arterial revascularisation and shorter
      intensive care stay were the significantly beneficial differences for patients in
      the redo-OPCAB group (p<0.05). The 3-year survival rate was higher in the redo
      OPCAB group with 81 +/- 12% versus 63 +/- 9%in the redo-ONCAB group. The quality
      of life survey did not reveal any significant differences between both groups.
      CONCLUSION: In conclusion, with our present retrospective study, we could
      demonstrate the safety and efficacy of the redo-OPCAB technique with even higher
      3-year survival rate. Both techniques seem to have similar impact on the outcome
      of patients.

PMID- 23561397
TI  - A great one steps down.

PMID- 23561398
TI  - Concern about interpretation of the data.

PMID- 23561399
TI  - Author's response.

PMID- 23561400
TI  - Assessing salivary biomarkers for analyzing orthodontic tooth movement.

PMID- 23561401
TI  - Authors' response.

PMID- 23561402
TI  - The time is now.

PMID- 23561403
TI  - Palatally impacted canines: the case for preorthodontic uncovering and autonomous
      eruption.

PMID- 23561404
TI  - Palatally impacted canines: the case for closed surgical exposure and immediate
      orthodontic traction.

PMID- 23561406
TI  - Dimensional changes of upper airway after rapid maxillary expansion: a
      prospective cone-beam computed tomography study.
AB  - INTRODUCTION: The aim of this prospective study was to use cone-beam computed
      tomography to assess the dimensional changes of the upper airway in orthodontic
      patients with maxillary constriction treated by rapid maxillary expansion.
      METHODS: Fourteen orthodontic patients (mean age, 12.9 years; range, 9.7-16
      years) were recruited. The patients with posterior crossbite and constricted
      maxilla were treated with rapid maxillary expansion as the initial part of their
      comprehensive orthodontic treatments. Before and after rapid maxillary expansion
      cone-beam computed tomography scans were taken to measure the retropalatal and
      retroglossal airway changes in terms of volume, and sagittal and cross-sectional
      areas. The transverse expansions by rapid maxillary expansion were assessed
      between the midlingual alveolar bone plates at the maxillary first molar and
      first premolar levels. The measurements of the before and after rapid maxillary
      expansion scans were compared by using paired t tests with the Bonferroni
      adjustment for multiple comparisons. RESULTS: After rapid maxillary expansion,
      significant and equal amounts of 4.8 mm of expansion were observed at the first
      molar (P = 0.0000) and the first premolar (P = 0.0000) levels. The width increase
      at the first premolar level (20.0%) was significantly greater than that at the
      first molar level (15.0%) (P = 0.035). As the primary outcome variable, the cross
      sectional airway measured from the posterior nasal spine to basion level was the
      only parameter showing a significant increase of 99.4 mm(2) (59.6%) after rapid
      maxillary expansion (P = 0.0004). CONCLUSIONS: These results confirm the findings
      of previous studies of the effect of rapid maxillary expansion on the maxilla.
      Additionally, we found that only the cross-sectional area of the upper airway at
      the posterior nasal spine to basion level significantly gains a moderate increase
      after rapid maxillary expansion.

PMID- 23561407
TI  - Changes of pulp-chamber dimensions 1 year after rapid maxillary expansion.
AB  - INTRODUCTION: The purpose of this study was to examine the effect of orthopedic
      forces on maxillary first molars' and maxillary central incisors' pulp chambers
      in children having rapid maxillary expansion as the only intervention compared
      with children having no orthodontic intervention by using cone-beam computed
      tomography images. METHODS: In this prospective controlled clinical study, we
      evaluated 60 maxillary first molars and 60 maxillary central incisors from 30
      children (18 boys, 12 girls) in the mixed dentition and during the pubertal
      growth period. The treated group had rapid maxillary expansion with the Haas
      expander, followed by 6 months of retention and 6 months of follow-up out of
      retention; the control group had no intervention during the study. Cone-beam
      computed tomography scans were taken initially and 1 year after the rapid
      maxillary expansion active phase. Initially, a 3-dimensional scrolling in all
      pulp chambers of the evaluated teeth was performed with Dolphin Imaging software
      (version 11.0; Dolphin Imaging & Management Solutions, Chatsworth, Calif) to
      describe the incidence of pulp-chamber calcifications. The dimensions of the pulp
      chambers of the molars and incisors were also investigated. Cross-sectional and
      longitudinal slices were used for each molar (coronal and axial slices) and
      incisor (sagittal and axial slices). The area (mm(2)) was obtained from 3 slices
      of each kind (6 measurements for each tooth). RESULTS: The results suggest that
      rapid maxillary expansion did not induce new pulp-chamber calcification. Also, it
      did not interfere in normal pulp-chamber dimension changes of the anchorage
      molars. CONCLUSIONS: The pulp chamber of the central incisors can be expected to
      be minimally wider 1 year after the therapy.

PMID- 23561408
TI  - Maxillary sinus floor extension and posterior tooth inclination in adolescent
      patients with Class II Division 1 malocclusion treated with maxillary first molar
      extractions.
AB  - INTRODUCTION: Our objective was to investigate potential associations between
      maxillary sinus floor extension and inclination of maxillary second premolars and
      second molars in patients with Class II Division 1 malocclusion whose orthodontic
      treatment included maxillary first molar extractions. METHODS: The records of 37
      patients (18 boys, 19 girls; mean age, 13.2 years; SD, 1.62 years) treated
      between 1998 and 2004 by 1 orthodontist with full Begg appliances were used in
      this study. Inclusion criteria were white patients with Class II Division 1
      malocclusion, sagittal overjet of >=4 mm, treatment plan including extraction of
      the maxillary first permanent molars, no missing teeth, and no agenesis.
      Maxillary posterior tooth inclination and lower maxillary sinus area in relation
      to the palatal plane were measured on lateral cephalograms at 3 time points: at
      the start and end of treatment, and on average 2.5 years posttreatment. Data were
      analyzed for the second premolar and second molar inclinations by using mixed
      linear models. RESULTS: The analysis showed that the second molar inclination
      angle decreased by 7 degrees  after orthodontic treatment, compared with
      pretreatment values, and by 11.5 degrees  at the latest follow-up, compared with
      pretreatment. There was evidence that maxillary sinus volume was negatively
      correlated with second molar inclination angle; the greater the volume, the
      smaller the inclination angle. For premolars, inclination increased by 15.4
      degrees  after orthodontic treatment compared with pretreatment, and by 8.1
      degrees  at the latest follow-up compared with baseline. The volume of the
      maxillary sinus was not associated with premolar inclination. CONCLUSIONS: We
      found evidence of an association between maxillary second molar inclination and
      surface area of the lower sinus in patients treated with maxillary first molar
      extractions. Clinicians who undertake such an extraction scheme in Class II
      patients should be aware of this potential association and consider appropriate
      biomechanics to control root uprighting.

PMID- 23561409
TI  - Estimation of periodontal ligament's equivalent mechanical parameters for finite
      element modeling.
AB  - INTRODUCTION: Young's modulus (E) and Poisson's ratio (v) of the periodontal
      ligament are needed in a finite element analysis for investigating the
      biomechanical behavior of a tooth, periodontal ligament, and bone complex.
      However, large discrepancies in E (0.01-1,750 MPa) and v (0.28-0.49) were
      reported previously. The objective of this study was to narrow the ranges and to
      provide equivalent E and v pairs suitable for finite element modeling of a tooth,
      periodontal ligament, and bone complex by using a reported crown load
      displacement relationship as the criterion. METHODS: A 3-dimensional finite
      element model of a 3-tooth, periodontal ligament, and bone complex, consisting of
      a maxillary central incisor with 2 adjacent teeth, from a cone-beam computed
      tomography scan was created. The dimensions, constraints, and loading condition
      were kept similar to those reported in the human study. With the load applied to
      the crown, both v and E were adjusted independently, and the corresponding crown
      displacements were calculated. The resulting load-displacement curves were
      compared with those reported in the human study. The mean absolute displacement
      difference method was used to find the best fit. The E and v pairs that generated
      the minimum mean absolute displacement difference were identified. RESULTS: The
      finite element model with 1 of the 3 E and v pairs (v = 0.35, E = 0.87 MPa; v =
      0.4, E = 0.71 MPa; and v = 0.45, E = 0.47 MPa) simulated the tooth, periodontal
      ligament, and bone complex well. The mean absolute displacement differences were
      0.0135, 0.0138, and 0.0138 mm, respectively; these are less than 8% of 0.175 mm,
      which was the crown displacement of the tooth, periodontal ligament, and bone
      complex under the load of 500 cN. CONCLUSIONS: The E and v values close to the 3
      pairs might be used for finite element modeling of the tooth, periodontal
      ligament, and bone complex.

PMID- 23561410
TI  - Apical root resorption: the dark side of the root.
AB  - INTRODUCTION: The diagnosis of apical root resorption is usually based on routine
      radiographs. However, these methods are limited because the images reflect the
      superimposition of the whole root structure and can lead to underestimation of
      the extent of apical root resorption. In this study, we aimed to determine the
      lengths of the labial and lingual surfaces of incisors with apical root
      resorption and compare them with the longest radicular length obtained on
      sagittal images of cone-beam computed tomography, and to create a qualitative
      visual scale of the different patterns of apical root resorption. METHODS: Eighty
      two incisors with apical root resorption from 25 patients had their labial and
      lingual root surfaces and the longest radicular lengths determined in the
      sagittal plane and compared. Five orthodontists, at 2 times, classified the
      images of each incisor according to a visual scale developed by the authors.
      RESULTS: There was no significant difference between the labial and lingual
      surfaces; however, the longest radicular length was significantly greater than
      the shortest surface length. The visual scale showed intraobserver agreement of
      0.615 and interobserver agreements of 0.74 and 0.52 at both times, respectively.
      CONCLUSIONS: The difference between the longest and shortest root lengths
      suggests that radiographic superimposition underestimates the extent of the
      resorption lesion. The proposed visual scale showed a frequency of agreement
      above 65% and a coefficient of reproducibility varying from moderate to
      substantial.

PMID- 23561412
TI  - Force levels in complex tooth alignment with conventional and self-ligating
      brackets.
AB  - INTRODUCTION: The force applied to the teeth is a variable of orthodontic
      treatment that can be controlled. Poor control of the applied force can lead to
      adverse biologic effects as well as undesirable tooth movements. The selected
      archwire-bracket combination is a primary determining factor in the force level
      applied to a tooth during orthodontic treatment. The aim of this research was to
      use an experimental biomechanical setup to measure forces generated during
      complex orthodontic tooth movements with various archwire-bracket combinations.
      METHODS: The materials consisted of 3 types of 0.022-in slot orthodontic
      brackets: (1) conventional brackets (Victory Series [3M Unitek, Monrovia, Calif]
      and Mini-Taurus [Rocky Mountain Orthodontics, Denver, Colo]), (2) self-ligating
      brackets (SmartClip [3M Unitek] and Time3 [American Orthodontics, Shegoygan,
      Wis]), and (3) a conventional low-friction bracket (Synergy [Rocky Mountain
      Orthodontics]); and 4 archwire types: (1) 0.012-in stainless steel (3M Unitek),
      (2) 0.0155-in coaxial (Advanced Orthodontics [Napflein, Dusseldorf, Germany]),
      (3) 0.012-in Orthonol (Rocky Mountain Orthodontics), and (4) 0.012-in Thermalloy
      (Rocky Mountain Orthodontics). Stainless steel ligatures and elastomeric rings
      were used. The materials were used in different combinations in a simulated
      malocclusion that represented a maxillary central incisor displaced 2 mm
      gingivally (x-axis) and 2 mm labially (z-axis). RESULTS: The lowest forces were
      measured when the brackets were combined with either the coaxial or the
      Thermalloy archwires; the forces ranged from 3.4 +/- 0.2 to 0.7 +/- 0.1 N in the
      x-axis direction, and from 4.5 +/- 0.3 to 0.5 +/- 0.1 N in the z-axis direction.
      The highest forces were measured in combination with stainless steel archwires;
      the forces ranged from 6.3 +/- 0.3 to 3.0 +/- 0.1 N in the x-axis direction, and
      from 6.3 +/- 0.3 to 1.7 +/- 0.1 N in the z-axis direction. CONCLUSIONS: We
      recommend 0.0155-in coaxial and 0.012-in Thermalloy archwires for leveling and
      alignment. Elastomeric rings, when used with conventional brackets, increased the
      force applied to the teeth.

PMID- 23561411
TI  - Botulinum neurotoxin type A in the masseter muscle: effects on incisor eruption
      in rabbits.
AB  - INTRODUCTION: Botulinum neurotoxins are responsible for the paralytic food
      poisoning, botulism. Commercial formulations such as botulinum neurotoxin type A
      are increasingly used for various conditions, including cosmetic recontouring of
      the lower face by injection of the large masseter muscles. The paralysis of a
      major muscle of mastication lowers occlusal force and thus might affect tooth
      eruption. The purpose of this study was to investigate the effects of unilateral
      masseter muscle injection of botulinum neurotoxin type A on the rate of eruption
      of incisors in a rabbit model. We hypothesized that the teeth would overerupt in
      an underloaded environment. METHODS: Forty rabbits were injected with either
      botulinum neurotoxin type A or saline solution in 1 masseter muscle. Mastication
      and muscle force production were monitored, and incisor eruption rate was
      assessed by caliper measurement of grooved teeth. RESULTS: The injection of
      saline solution had no effect. The masseter muscle injected with botulinum
      neurotoxin type A showed a dramatic loss of force 3 weeks after injection despite
      apparently normal mastication. Incisor eruption rate was significantly decreased
      for the botulinum neurotoxin type A group, an effect attributed to decreased
      attrition. CONCLUSIONS: This study has implications for orthodontics. Although
      findings from ever-growing rabbit incisors cannot be extrapolated to human teeth,
      it is clear that botulinum neurotoxin type A caused a decrease in bite force that
      could influence dental eruption.

PMID- 23561413
TI  - Serum PTHrP level as a biomarker in assessing skeletal maturation during
      circumpubertal development.
AB  - INTRODUCTION: Many investigators have studied the cellular organization and the
      local and systemic factors regulating endochondral bone growth in the growth
      plate and condylar cartilage. Parathyroid hormone-related protein (PTHrP) and
      Indian hedgehog protein have been reported to regulate multiple steps during such
      skeletal morphogenesis. The aims of this study were to quantify serum PTHrP
      levels at 6 cervical vertebral stages and to correlate serum PTHrP levels to the
      6 skeletal maturation stages for use as a biologic indicator of skeletal
      maturation. METHODS: Mean serum PTHrP levels were measured in 90 subjects
      categorized into 6 cervical vertebral stages. RESULTS: Mean serum PTHrP levels
      were significantly higher in the late pubertal stages than in the early pubertal
      stages. Pearson correlation showed that serum PTHrP levels had a positive
      correlation with cervical vertebral maturation stages from the prepubertal to the
      late pubertal stages, and a negative correlation from the late pubertal to the
      postpubertal stages. CONCLUSIONS: Peak serum PTHrP levels do not correlate with
      early pubertal stages characterized by maximum growth increments. Hence, the
      validity of using serum PTHrP levels to predict peak growth velocity is
      questionable.

PMID- 23561414
TI  - Maxillary lateral incisor morphology and palatally displaced canines: a case
      controlled cone-beam volumetric tomography study.
AB  - INTRODUCTION: The goal of this study was to compare the dimensions of maxillary
      lateral incisors in subjects with and without palatally displaced canines.
      METHODS: An experimental group of 40 patients with 46 palatally displaced canines
      (20 in boys, 26 in girls; mean age, 13.9 years; range, 10.5-15.9 years) was
      selected from the records of patients referred to a radiology practice
      specializing in cone-beam volumetric tomography imaging. The palatally displaced
      canine group was age- and sex-matched with 30 normal subjects with 60 canines (26
      in boys, 34 in girls; mean age, 13.8 years; range, 10.4-15.7 years). Cone-beam
      volumetric tomography DICOM files were imported into Dolphin Imaging software
      (version 11.0; Dolphin Imaging & Management Solutions, Chatsworth, Calif), and
      the volumetric images were reoriented with the long axis of the lateral incisor
      vertical and then reconstructed into images of a sagittal slice through the
      maxillary lateral incisors and 3 axial slices across the maxillary lateral
      incisor root. The linear variables of the maxillary lateral incisors were
      measured by using digital measurement tools. The widths of the maxillary lateral
      incisor roots were registered at the cementoenamel junction level, 4 mm apical to
      the cementoenamel junction level and 8 mm apical to the cementoenamel junction
      level. An independent t test was used to test for differences between the groups,
      because the data were normally distributed. RESULTS: In the group with palatally
      displaced canines, the mean length of the maxillary lateral incisors was 2.1 mm
      shorter (P <0.001), and the mean root width was smaller, especially in the
      buccolingual dimension, by 0.7 mm (P <0.001). CONCLUSIONS: Lateral incisors
      adjacent to palatally displaced canines were smaller compared with those adjacent
      to normal canines.

PMID- 23561415
TI  - Etiologic factors for buccal and palatal maxillary canine impaction: a
      perspective based on cone-beam computed tomography analyses.
AB  - INTRODUCTION: The aim of this research was to identify the etiologic factors
      associated with palatally impacted canines and buccally impacted canines in a
      Chinese population by using the cone-beam computed tomography technique. METHODS:
      Pretreatment cone-beam computed tomography scans of 170 Chinese subjects with
      impacted maxillary canines and 170 age- and sex-matched subjects without
      impaction were used. Impacted canine subjects were divided into 2 groups: those
      with palatally impacted canines and those with buccally impacted canines. One
      rater analyzed the cone-beam computed tomography data for qualitative and
      quantitative variables of the teeth, dental arch, and skeletal components. The
      measurements were compared by using analytical statistical methods. RESULTS: The
      mesiodistal dimension of the lateral incisor was significantly smaller in the
      palatally impacted canine group than in the other group (by an average of 0.4-0.5
      mm; analysis of variance [ANOVA], P <0.001). Both anterior maxillary dental
      (interpremolar) width and skeletal width (interjugal points) in the buccally
      impacted canine group were significantly smaller than in the palatally impacted
      canine and control groups (ANOVA, P <0.001), whereas the intermolar widths and
      posterior mandibular widths were similar among the groups. The groups with
      palatally impacted or buccally impacted canines had significantly increased
      prevalence values of peg-shaped lateral incisors and incisor impaction,
      respectively (chi-square or Fisher exact tests, P <0.001). After excluding
      subjects who also had lateral incisor anomalies, the prevalence values of
      supernumerary teeth, missing premolars, or third molars combined were not
      different among the impaction and control groups. The average mesiodistal
      location of the canine cusp tip was significantly different between the buccally
      impacted canines and the palatally impacted canines groups; it was distal and
      mesial to the lateral incisor long axis, respectively. CONCLUSIONS: In Chinese
      subjects, buccal canine impaction is mostly associated with anterior transverse
      (dental and skeletal) deficiency and incisor impaction, whereas palatal impaction
      is mostly associated with small or missing lateral incisors, consistent with the
      guidance theory. Likely, preimpaction migrations of the canines are mainly buccal
      for buccal impactions and excessively mesiopalatal for palatal impactions.

PMID- 23561416
TI  - Periodontal ligament distraction: esthetics and occlusal stability at the 2-year
      follow-up.
AB  - Dental distraction is an orthodontic tooth movement technique that allows closure
      of extraction spaces, usually of premolars, in periods from 1 to 3 weeks, by
      bodily retraction of the canine. This article reports on canine distalization by
      using a distractor device obtained from a conventional hyrax screw. The patient
      was an adolescent boy, aged 17 years 9 months, who came to the clinic with the
      chief complaint of tooth crowding. The clinical examination showed a convex
      profile, retroclined and protruded maxillary incisors, buccally tipped and
      protruded mandibular incisors, and a Class I malocclusion. The treatment
      comprised extractions and rapid canine distraction procedures. Pretreatment,
      posttreatment, and 2-year follow-up records are shown and demonstrate that dental
      distraction is a viable alternative of treatment. With this treatment strategy,
      satisfactory results were obtained without additional anchorage devices,
      achieving an attractive smile and optimal occlusion. The main considerations
      about the treatment alternatives and their clinical concerns are discussed.

PMID- 23561417
TI  - Two-phase orthodontic treatment of a complex malocclusion: giving up efficiency
      in favor of effectiveness, quality of life, and functional rehabilitation?
AB  - The interceptive orthodontic treatment of patients with complex dentofacial
      abnormalities is frequently inefficient and produces less than ideal outcomes.
      Therefore, postponing therapy to a single-phase surgical-orthodontic approach
      might be considered a reasonable option. However, other relevant aspects of the
      patient's quality of life, such as possible psychosocial problems and functional
      impairments, should also be considered before deciding whether to intercept a
      severe dentofacial malocclusion while the patient is still growing, or wait and
      treat later. This case report describes the nonsurgical treatment of a young
      patient with a severe Class III open-bite malocclusion associated with a cervical
      cystic lymphangioma. Despite the poor interceptive therapy prognosis, a 2-phase
      approach was effective. A reflection about giving up efficiency in favor of
      effectiveness, functional rehabilitation, and the patient's quality of life is
      included.

PMID- 23561418
TI  - Early treatment of an ectopic premolar to prevent molar-premolar transposition.
AB  - Orthodontic treatment is planned on an individual, case-by-case basis after
      thoroughly considering the patient's overall facial and dental characteristics,
      the expected duration of treatment, costs, patient preferences, and the
      orthodontist's experience. This article reports the treatment of a patient with a
      maxillary premolar-molar transposition in the permanent dentition that was
      successfully managed with orthodontic treatment. A girl, aged 10 years 2 months,
      came for treatment with an ectopic maxillary left premolar. Radiographic analysis
      indicated a developing complete transposition of the maxillary left premolar. The
      patient was treated with extraction of the deciduous molar and surgical exposure
      and ligation of the premolar. Eruption was properly guided, and the correct order
      of the 2 teeth was restored in the arch. This challenging treatment approach is
      described in detail, including the mechanics used to align the ectopic premolar.
      Early treatment can, in many cases, prevent a molar-premolar transposition.

PMID- 23561419
TI  - Dens evaginatus: the hornet's nest of adolescent orthodontics.
AB  - Dens evaginatus is a rare dental anomaly that occurs during tooth development and
      results in an abnormal protrusion from the occlusal surface of the affected
      tooth, often in the area of the central groove between the buccal and lingual
      cusps. Of clinical importance to the orthodontist is that these occlusal
      tubercles fracture easily or can be worn away, resulting in direct pulp exposure
      in a noncarious tooth. This can cause severe complications, including loss of
      tooth vitality, facial infection in the form of an abscess or cellulitis, or
      osteomyelitis of the jaw. If extraction of premolars is indicated for orthodontic
      treatment after careful diagnosis and treatment planning, it is paramount to
      establish the health of the premolars that will remain in the dentition before
      extracting the teeth.

PMID- 23561420
TI  - Predicting tooth-size discrepancy: A new formula utilizing revised landmarks and
      3-dimensional laser scanning technology.
AB  - INTRODUCTION: The goal of this study was to develop a more accurate formula to
      forecast tooth-size discrepancies in patients based on not only the size of the
      whole teeth but also functional arch components derived from normal cusp-fossa
      interdigitation that should be obtained as the final treatment goal. METHODS: A
      total of 141 dental casts from Dr Larry Andrews' collection of "normal
      occlusions" that never received orthodontic treatment were scanned with an Ortho
      Insight 3D Laser Scanner (Motion View Software, Chattanooga, Tenn). Individual
      tooth sizes and portions of tooth sizes were measured with the Motion View
      Software. For each set of models, potential tooth-size discrepancies were
      calculated by using both the original Bolton analysis and the new Johnson/Bailey
      analysis developed by this team at the University of California at San Francisco
      (UCSF). Six tooth-size discrepancy ratios were computed and included the Bolton
      (2) and the new (4) Johnson/Bailey analysis ratios for the anterior arch
      component, posterior arch component, and overall ratio of the maxillary and
      mandibular arches. The Johnson/Bailey analysis utilized different landmarks and
      groups of teeth. It consequently divided the maxillary segment by the mandibular
      segment, in contrast to the Bolton ratios, which divided the mandibular sums by
      the maxillary totals. RESULTS: The Bolton anterior segment ratio ranged from
      70.68 to 84.81, with a mean of 77.91 (SD, 2.43) (3.1%). The Bolton overall ratio
      ranged from 86.19 to 96.62, with a mean of 91.64 (SD, +/-1.74) (1.8%). The
      Johnson/Bailey posterior discrepancy ratio ranged from 0.98 to 1.23, with a mean
      of 1.10 (SD, +/-0.04) (3.6%). Its anterior discrepancy ratio ranged from 0.91 to
      1.14, with a mean of 1.03 (SD, +/-0.04) (3.9%). The Johnson/Bailey overall
      discrepancy ratio ranged from 0.98 to 1.15, with a mean of 1.06 (SD, +/-0.03)
      (2.8%). CONCLUSIONS: Two methods were used to forecast tooth-size discrepancies
      between opposing arches in a sample with clinically acceptable occlusions. The
      new approach provided more specific ratios utilizing more clinically relevant
      functional arch components derived from dental cusp-fossa interdigitation.

PMID- 23561421
TI  - Litigation, legislation & ethics. Minor differences.

PMID- 23561422
TI  - Multiplicity 2: multiple treatments and multiple outcomes.

PMID- 23561423
TI  - Calculating an estimate of tissue integrated activity in 18F-FDG PET imaging
      using one SUV value.
AB  - BACKGROUND: A kinetic model analysis was recently proposed to estimate the 18F
      fluorodeoxyglucose (18F-FDG) integrated activity in an arbitrary tissue that uses
      tracer uptake and release rate constants. The aim of the current theoretical
      paper was to estimate 18F-FDG integrated activity using one standardized uptake
      value (SUV). METHODS: A further kinetic model analysis allowed us to derive an
      analytical solution for integrated activity determination, involving both
      irreversible and reversible trapping. It only uses SUV, which is uncorrected for
      18F physical decay (SUVuncorr, in g.mL-1) and is assessed about its peak value.
      Measurement uncertainty of the estimate was also assessed. RESULTS: In a tissue
      (volume V, in mL) that irreversibly traps 18F-FDG, the total number of
      disintegrations can be estimated as: AC = 162 * 105 * SUVuncorr * V * ID / W (ID,
      injected dose, in MBq; W, patient's weight, in kg), where SUVuncorr is a mean
      over V and is assessed between 55 and 110 min after tracer injection. The
      relative uncertainty ranges between 18% and 30% (the higher the uptake, the lower
      the uncertainty). Comparison with the previous Zanotti-Fregonara's model applied
      to foetus showed less than 16% difference. Furthermore, calculated integrated
      activity estimates were found in good agreement with Mejia's results for healthy
      brain, lung and liver that show various degrees of tracer trapping reversibility
      and various fractions of free tracer in blood and interstitial volume.
      CONCLUSION: Estimation of integrated activity in an arbitrary tissue using one
      SUV value is possible, with measurement uncertainty related to required
      assumptions. A formula allows quick estimation that does not underestimate
      integrated activity so that it could be helpful in circumstances such as
      accidental exposure, or for epidemiologic purposes such as in patients having
      undergone several examinations.

PMID- 23561424
TI  - Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy
      of gamma-tocotrienol, a promising radiation countermeasure.
AB  - This study aimed to determine the role of granulocyte colony-stimulating factor
      (G-CSF), induced by a promising radiation countermeasure, gamma tocotrienol
      (GT3), in protecting mice from lethal doses of ionizing radiation. CD2F1 mice
      were injected with an optimal dose of GT3 and a G-CSF antibody, and their 30-d
      survival was monitored. An appropriate antibody isotype was used as a control.
      Multiplex Luminex was used to analyze GT3-induced cytokines. G-CSF neutralization
      by exogenous administration of a G-CSF antibody was confirmed by analyzing serum
      cytokine levels. Our results demonstrate that GT3 significantly protected mice
      against ionizing radiation, and induced high levels of G-CSF in peripheral blood
      24h after administration. Injection of a G-CSF neutralizing antibody to the GT3
      treated mice resulted in complete neutralization of G-CSF and abrogation of its
      protective efficacy. Administration of a G-CSF antibody did not affect levels of
      other cytokines induced by GT3. Histopathology of bone marrow from GT3-treated
      and -irradiated mice demonstrated protection of the hematopoietic tissue, and
      also that such protection was abrogated by administering a G-CSF antibody. Our
      results suggest that induction of high levels of G-CSF by GT3 administration is
      responsible for its protective efficacy against radiation injury.

PMID- 23561425
TI  - Impact of pre-emptive contact precautions for outborn neonates on the incidence
      of healthcare-associated meticillin-resistant Staphylococcus aureus transmission
      in a Japanese neonatal intensive care unit.
AB  - BACKGROUND: The neonatal intensive care unit (NICU) is a high-risk setting for
      transmission of meticillin-resistant Staphylococcus aureus (MRSA). Very few
      studies have investigated the impact of pre-emptive contact precautions applied
      to outborn neonates transferred to an NICU on the incidence of healthcare
      associated (HA)-MRSA transmission. AIM: To assess the efficacy of pre-emptive
      contact precautions for outborn neonates implemented in an NICU. METHODS: A
      before-and-after intervention study was conducted in the NICU of Kobe University
      Hospital. Pre-emptive contact precautions for outborn neonates were introduced in
      September 2008. The period before the introduction of pre-emptive contact
      precautions (January 2007-August 2008) was compared with the period after the
      introduction of pre-emptive contact precautions (September 2008-December 2010).
      Data for all admitted neonates, neonates who stayed in the NICU for more than
      three days, length of NICU stay, incidence of MRSA-positive outborn neonates on
      admission, hand hygiene compliance and incidence of HA-MRSA transmission were
      compared between the two periods. FINDINGS: There were no significant differences
      in the percentage of outborn patients admitted to the NICU, percentage of
      patients who stayed in the NICU for more than three days, length of NICU stay,
      and incidence of MRSA-positive outborn patients at NICU admission between the
      groups enrolled before and after the introduction of pre-emptive contact
      precautions. However, hand hygiene compliance increased, and the incidence of HA
      MRSA transmission reduced significantly from 3.5/1000 to 1.3/1000 patient-days
      after the introduction of pre-emptive contact precautions (P < 0.0001).
      CONCLUSION: Pre-emptive contact precautions for outborn neonates were effective
      in reducing the incidence of HA-MRSA transmission in a Japanese NICU.

PMID- 23561426
TI  - Discussion.

PMID- 23561427
TI  - Multiple aneurysms of the radial artery in a woman with neurofibromatosis type 1
      presenting as aneurysm rupture.
AB  - A 48-year-old woman with neurofibromatosis type 1 (NF1) experienced progressive
      forearm swelling coupled with impending compartment syndrome. Computed tomography
      angiography revealed a ruptured aneurysm of the proximal radial artery, multiple
      fusiform radial artery aneurysms, and a high independent ulnar artery origin.
      Compartment syndrome required prompt hematoma evacuation. Radial artery
      reconstruction, technically demanding due to vessel wall fragility, was deemed
      unnecessary because of satisfactory blood supply to the hand. Histologic findings
      indicated NF1-related vascular abnormalities also in the apparently normal radial
      artery as well as in a forearm vein, suggesting diffused vasculopathy. This case
      report is the first on ruptured radial artery aneurysm in NF1-related
      polianeurysmatic degeneration. 

PMID- 23561428
TI  - Distal revascularization and interval ligation procedure for radial-basilic
      forearm transposition arteriovenous fistula.
AB  - The distal revascularization and interval ligation procedure is commonly
      performed for steal syndrome in upper arm arteriovenous accesses and is rarely
      performed in the forearm. We present a case of distal revascularization and
      interval ligation procedure performed for a 60-year-old male who presented with a
      3-month history of a nonhealing ulcer of his left middle finger as a result of
      ischemic steal syndrome 4 years after having a left radial-basilic forearm
      transposition arteriovenous fistula. 

PMID- 23561429
TI  - Endovascular treatment of a symptomatic extracranial vertebral artery aneurysm.
AB  - Aneurysms of the extracranial vertebral artery are uncommon, with most cases
      attributed to penetrating head and neck trauma. We report a 29-year-old man with
      a symptomatic proximal extracranial vertebral artery aneurysm of unclear
      etiology. This patient's aneurysm was definitively treated after a successful
      balloon occlusion test of his affected vertebral artery. An endovascular approach
      was used combining coil embolization of the distal vertebral artery and a covered
      stent graft in the subclavian. Although aneurysms of this size and location are
      traditionally repaired with open aneurysmectomy, we show that endovascular
      approaches can be a safe and effective alternative. 

PMID- 23561430
TI  - Effect of lipid-modifying drug therapy on survival after abdominal aortic
      aneurysm repair.
AB  - BACKGROUND: Lipid-modifying drug therapy (LMDT) is recommended in all patients
      having coronary or noncoronary atherosclerotic disease. However, the effect of
      LMDT after abdominal aortic aneurysm (AAA) repair, especially in the absence of
      other atherosclerotic manifestations, is unclear. We examined the distribution of
      prevalence of LMDT among patients undergoing AAA repair and its effect on
      survival in the presence and absence of other atherosclerotic diseases. METHODS:
      We identified patients treated at University of Alabama at Birmingham between
      1985 and 2010 who had a prior AAA repair. Information was collected from health
      system medical charts, medical communication, and national death indices. We
      assessed the predictors of prevalence of LMDT by univariate analysis using t-test
      for continuous and chi(2) test for categorical variables, and then performed
      multivariate logistic regression. The survival was determined using Kaplan-Meier
      plots, and adjusted hazard ratios were calculated using Cox proportion
      regression. RESULTS: A total of 2063 patients underwent AAA repair procedure. Of
      these, 9% were African-American, and 20% were female. Thirty-five percent
      received LMDT, and 32% died during the follow-up period of up to 240 months.
      Significant predictors for being on LMDT included white race (odds ratio [OR],
      1.6; 95% confidence interval [CI], 1.1-2.2), presence of other atherosclerotic
      disease or diabetes (OR, 2.4; 95% CI, 1.9-3.0), hypertension (OR, 4.0; 95% CI,
      3.1-5.2), smoking (OR, 1.6; 95% CI, 1.2-2.1), and endovascular AAA repair (OR,
      1.9; 95% CI, 1.5-2.3). LMDT was associated with improved survival (hazard ratio,
      0.6; 95% CI, 0.5-0.8) after controlling for traditional risk factors, diabetes,
      and other atherosclerotic diseases. CONCLUSIONS: LMDT after AAA is associated
      with an increased survival compared with patients who were not using drug therapy
      for dyslipidemia. Aggressive management of dyslipidemia should be considered in
      all patients undergoing AAA repair irrespective of other atherosclerotic disease
      status and risk factor profile.

PMID- 23561431
TI  - Lumbar artery pseudoaneurysm as a late complication of osteomyelitis with
      vertebral body destruction.
AB  - We report the case of a 79-year-old patient whose acute back pain revealed a 9-cm
      nonruptured lumbar artery pseudoaneurysm occurring 5 years after a vertebral body
      osteomyelitis that induced a significant vertebral destruction. She underwent an
      urgent percutaneous selective arterial embolization. Lumbar artery false aneurysm
      should, thus, be suspected as a possible etiology of any new painful symptoms in
      patients suffering from a chronic vertebral destructive disease. 

PMID- 23561432
TI  - Hypogastric and lumbar artery bypasses to restore gluteal perfusion after open
      aortoiliac aneurysm repair.
AB  - Gluteal ischemia is a rare but often fatal complication after open abdominal
      aortic aneurysm repair. A 67-year-old man with an aortoiliac aneurysm presented
      with a patent right internal iliac artery (IIA) and an occluded left IIA. A
      bifurcated graft replacement was performed with both limbs of the graft
      anastomosed to the external iliac arteries. The right IIA was ligated and the
      inferior mesenteric artery was reimplanted. Postoperatively, the patient
      developed right gluteal ischemia. Hypogastric and lumbar artery bypasses were
      immediately performed and the patient recovered without gait disturbance. This
      treatment prevented potentially fatal necrosis of the buttock. 

PMID- 23561433
TI  - Efficacy of thoracic endovascular stent repair for chronic type B aortic
      dissection with aneurysmal degeneration.
AB  - BACKGROUND: The Food and Drug Administration has approved devices for
      endovascular management of thoracic endovascular aortic aneurysm repair (TEVAR);
      however, limited data exist describing the outcomes of TEVAR for aneurysms
      attributable to chronic type B aortic dissection (cTBAD). This study was
      undertaken to determine the results of endovascular treatment of cTBAD with
      aneurysmal degeneration. METHODS: A retrospective analysis of all patients
      treated for cTBAD with aneurysmal degeneration at the University of Florida from
      2004 to 2011 was performed. Computed tomograms with centerline reconstruction
      were analyzed to determine change in aortic diameter, relative proportions of
      aortic treatment lengths, and false lumen perfusion status. Reintervention and
      mortality were estimated using life-tables. Cox regression analysis was completed
      to predict mortality. RESULTS: Eighty patients underwent TEVAR for aneurysm due
      to cTBAD (mean age [+/- standard deviation], 60 +/- 13 years [male, 87.5%; n =
      70]; median follow-up, 26 [range, 1-74] months). Median time from diagnosis of
      TBAD to TEVAR was 16 (range, 1-72) months. Prior aortic root/arch replacement had
      been performed in 29% (n = 23) at a median interval of 28.5 (range, 0.5-312)
      months. Mean preoperative aneurysm diameter was 62.0 +/- 9.9 mm. In 75% (n = 60)
      of cases, coverage was proximal to zone 3, and 24% (n = 19) underwent carotid
      subclavian bypass or other arch debranching procedure. Spinal drains were used in
      78% (pre-op 71%, n = 57; post-op 6%, n = 5). Length of stay was 6.5 +/- 4.7 days
      with a composite morbidity of 26% and in-hospital mortality of 2.5% (n = 2).
      Overall neurologic event rate was 17% (spinal cord ischemia 10% [n = 8], with a
      permanent deficit observed in 6.2% [n = 5]; stroke 7.5%). Aneurysm diameter
      reduced or stabilized in 65%. The false lumen thrombosed completely within the
      thoracic aorta in 52%, and reintervention within the treated aortic segment was
      required in 16% (n = 13).One- and 3-year freedom from reintervention (with 95%
      confidence interval [CI]) was 80% (range, 68%-88%) and 70% (range, 57%-80%),
      respectively. Survival at 1 and 5 years was 89% (range, 80%-94%) and 70% (range,
      55%-81%) and was not significantly different among patients requiring
      reintervention or experiencing favorable aortic remodeling. Multivariable
      analysis identified coronary artery disease (hazard ratio [HR], 6.4; 95% CI, 2.3
      17.7; P < .005), prior infrarenal aortic surgery (HR, 8.6; 95% CI, 2.3-31.7; P =
      .001), and congestive heart failure (HR, 11.9; 95% CI, 1.9-73.8; P = .008) as
      independent risk factors for mortality. Hyperlipidemia was found to be protective
      (HR, 0.2; 95% CI, 0.05-0.6; P = .004). No significant difference in predictors of
      mortality were found between patients who underwent reintervention vs those who
      did not (P = .2). CONCLUSIONS: TEVAR for cTBAD with aneurysmal degeneration can
      be performed safely but spinal cord ischemia rates may be higher than previously
      reported. Liberal use of procedural adjuncts to reduce this complication, such as
      spinal drainage, is recommended. Reintervention is common, but long-term survival
      does not appear to be impacted by remediation.

PMID- 23561434
TI  - Preliminary experience with superparamagnetic iron oxide-enhanced dynamic
      magnetic resonance imaging and comparison with contrast-enhanced computed
      tomography in endoleak detection after endovascular aneurysm repair.
AB  - OBJECTIVE: Contrast-enhanced computed tomography (CE-CT) has been commonly used
      for follow-up imaging after endovascular aneurysm repair (EVAR), but it is
      difficult to use on patients with renal insufficiency. Superparamagnetic iron
      oxide (SPIO) particles, contrast medium for magnetic resonance imaging (MRI) that
      has been widely used for detection of the liver tumor, rarely affects renal
      function. The present study examined SPIO-enhanced dynamic MRI as a potential
      alternative to CE-CT for detection of endoleaks after EVAR. METHODS:
      Institutional review board approval was obtained for this prospective study.
      Twenty-three consecutive patients with normal renal function were evaluated using
      both CE-CT and SPIO-enhanced MRI within 2 weeks after EVAR. The median interval
      between the two modalities was 2 days. SPIO-enhanced MRI was performed at 1.5 T
      with T1-weighted, SPIO-enhanced dynamic, and postcontrast T1-weighted gradient
      echo sequences. The CE-CT protocol consisted of triple scans. Two experienced,
      blinded observers evaluated all images. Consensus reading of CE-CT and SPIO-MRI
      was defined as the reference standard. Interobserver, intraobserver, and
      intermodality agreement for endoleak detection was assessed by kappa statistics.
      RESULTS: A total of 11 type II endoleaks originating from either the lumbar or
      inferior mesenteric artery were detected. Eight were able to be detected by CE-CT
      (8/11:73%) and 10 (10/11:91%) by SPIO-enhanced MRI. Interobserver (kappa = 0.91;
      95% CI, 0.74-1.00) and intraobserver agreement for MRI (kappa = 1.00) were
      excellent. Intermodality agreement for endoleak detection was moderate (kappa =
      0.63; 95% CI, 0.32-0.94; and kappa = 0.62; 95% CI, 0.29-0.95 for observers A and
      B, respectively). CONCLUSIONS: SPIO-enhanced MRI could represent a useful
      alternative to CE-CT, as it offers excellent interobserver, intraobserver
      agreement, and could detect more endoleaks than CE-CT.

PMID- 23561435
TI  - Minimally invasive surgical repair of iliac artery endofibrosis.
AB  - Iliac artery endofibrosis is an uncommon condition, which should be considered in
      young athletes with exertional lower limb symptoms. Imaging often appears normal
      at rest, and the diagnosis can be missed if clinical assessment is inadequate. We
      report a successful case of entirely minimally invasive surgical treatment for
      iliac artery endofibrosis in a 41-year-old cyclist. This novel technique offers
      superior potential for intraoperative assessment and aids enhancement in recovery
      after surgery. It is likely to be particularly appealing to elite athletes. 

PMID- 23561436
TI  - Short telomeres flirt with stem cell commitment.
AB  - High expression of telomerase in embryonic stem cells (ESCs) is important for
      their maintenance, but whether telomere length affects lineage commitment is
      unknown. In this issue of Cell stem cell, Pucci et al. (2013) reveal that ESCs
      with short telomeres exhibit unstable differentiation by inducing altered DNA
      methylation.

PMID- 23561437
TI  - To be immunogenic, or not to be: that's the iPSC question.
AB  - The unexpected finding that autologous induced pluripotent stem cell (iPSC)
      derived teratomas are immunogenic in syngeneic hosts sparked pessimism over their
      therapeutic potential; however, two recent reports (Guha et al., 2013 and Araki
      et al., 2013; the latter in this issue of Cell stem cell) contradict previous
      findings, showing no immunogenicity of in vitro differentiated syngeneic iPS
      derived cells and supporting their safety.

PMID- 23561438
TI  - The nexus of Tet1 and the pluripotency network.
AB  - Resetting DNA methylation and reactivation of pluripotency genes are late events
      in the formation of iPSCs. Recent work by Costa et al. (2013) and Gao et al.
      (2013) has examined the role of Tet proteins in the hydroxymethylation of
      pluripotency genes, with the latter replacing Oct4 with Tet1 for reprogramming.

PMID- 23561439
TI  - If a stem cell dies in the crypt, and no one is around to see it....
AB  - Two recent studies continue the debate regarding lineage and hierarchy in the
      intestinal epithelium. One reports that quiescent crypt cells are Paneth cell
      precursors (Buczacki et al., 2013). The second shows that tamoxifen induces
      apoptosis in crypt cells and that suppressing apoptosis alters lineage tracing
      patterns (Zhu et al., 2013).

PMID- 23561440
TI  - This niche is a maze; an amazing niche.
AB  - The cellular identity of niche cells that regulate hematopoietic stem cell (HSC)
      self-renewal and differentiation has been debated for several years. Two recent
      studies in Nature (Ding and Morrison, 2013; Greenbaum et al., 2013) have shed
      light into the bone marrow stromal subsets making CXCL12, a chemokine critical
      for HSC maintenance.

PMID- 23561441
TI  - Enhanced efficiency of human pluripotent stem cell genome editing through
      replacing TALENs with CRISPRs.

PMID- 23561443
TI  - Reactive glia in the injured brain acquire stem cell properties in response to
      sonic hedgehog. [corrected].
AB  - As a result of brain injury, astrocytes become activated and start to proliferate
      in the vicinity of the injury site. Recently, we had demonstrated that these
      reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres
      in vitro. In the present study, we demonstrate that it is only invasive injury,
      such as stab wounding or cerebral ischemia, and not noninvasive injury
      conditions, such as chronic amyloidosis or induced neuronal death, that can
      elicit this increase in plasticity. Furthermore, we find that Sonic hedgehog
      (SHH) is the signal that acts directly on the astrocytes and is necessary and
      sufficient to elicit the stem cell response both in vitro and in vivo. These
      findings provide a molecular basis for how cells with neural stem cell lineage
      emerge at sites of brain injury and imply that the high levels of SHH known to
      enter the brain from extraneural sources after invasive injury can trigger this
      response.

PMID- 23561442
TI  - Lin28: primal regulator of growth and metabolism in stem cells.
AB  - In recent years, the highly conserved Lin28 RNA-binding proteins have emerged as
      factors that define stemness in several tissue lineages. Lin28 proteins repress
      let-7 microRNAs and influence mRNA translation, thereby regulating the self
      renewal of mammalian embryonic stem cells. Subsequent discoveries revealed that
      Lin28a and Lin28b are also important in organismal growth and metabolism, tissue
      development, somatic reprogramming, and cancer. In this review, we discuss the
      Lin28 pathway and its regulation, outline its roles in stem cells, tissue
      development, and pathogenesis, and examine the ramifications for re-engineering
      mammalian physiology.

PMID- 23561444
TI  - Short telomeres in ESCs lead to unstable differentiation.
AB  - Functional telomeres are critical for stem cell proliferation; however, whether
      they are equally important for the stability of stem cell differentiation is not
      known. We found that mouse embryonic stem cells (ESCs) with critically short
      telomeres (Tert(-/-) ESCs) initiated normal differentiation after leukemia
      inhibitory factor (LIF) withdrawal but, unlike control ESCs, failed to maintain
      stable differentiation when LIF was reintroduced to the growth medium. Tert(-/-)
      ESCs expressed higher levels of Nanog and, overall, had decreased genomic CpG
      methylation levels, which included the promoters of Oct4 and Nanog. This unstable
      differentiation phenotype could be rescued by telomere elongation via
      reintroduction of Tert, via suppression of Nanog by small hairpin RNA (shRNA)
      knockdown, or via enforced expression of the de novo DNA methyltransferase 3b.
      These results demonstrate an unexpected role of functional telomeres in the
      genome-wide epigenetic regulation of cell differentiation and suggest a
      potentially important role of telomere instability in cell fate during
      development or disease.

PMID- 23561445
TI  - Features and costs of patients admitted for cardiac arrhythmias in Spain.
AB  - AIM: Cardiac rhythm alterations are a frequent cause of hospital admission.
      However, we do not know their characteristics and economic costs. We have
      analyzed the epidemiology and cost of hospitalizations due to cardiac arrhythmias
      in the National Health System. METHODS: The characteristics and costs were
      reviewed in patients admitted with a principal diagnosis of cardiac arrhythmia
      (1997-2010;diagnosis related groups [DRG] -138 and 139 of the National Health
      System minimum data base set). Atrial fibrillation/flutter accounted for 65% of
      these DRGs. The secondary diagnoses prevalent in such DRGs were also reviewed.
      RESULTS: Hospitalizations due to cardiac arrhythmias were approximately 26.000
      per year and close to 1.6% for mortality. In 2010 there were 26.421
      hospitalizations with an estimated cost of 65 million Euros. Frequent
      comorbidities were recorded, such as hypertension (43%), heart failure (12%) or
      diabetes mellitus (20%). A total of 43% were admitted to cardiology and 36% to
      internal medicine. CONCLUSIONS: During the period 1997-2010, there was a
      significant annual number of hospitalizations for cardiac arrhythmias (mainly
      atrial fibrillation), with measurable costs, in Spain. More than one third were
      attended by internists.

PMID- 23561448
TI  - A maternal high-protein diet predisposes female offspring to increased fat mass
      in adulthood whereas a prebiotic fibre diet decreases fat mass in rats.
AB  - The negative effects of malnourishment in utero have been widely explored; the
      effects of increased maternal macronutrient intake are not known in relation to
      high fibre, and have been inconclusive with regard to high protein. In the
      present study, virgin Wistar dams were fed either a control (C), high-protein (40
      %, w/w; HP) or high-prebiotic fibre (21.6 %, w/w; HF) diet throughout pregnancy
      and lactation. Pups consumed the C diet from 3 to 14.5 weeks of age, and then
      switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray
      absorptiometry scan and an oral glucose tolerance test were performed and plasma
      satiety hormones measured. The final body weight and the percentage of body fat
      were significantly affected by the interaction between maternal diet and
      offspring sex: weight and fat mass were higher in the female offspring of the HP
      v. HF dams. No differences in body weight or fat mass were seen in the male
      offspring. There was a significant sex effect for fasting and total AUC for
      ghrelin and fasting GIP, with females having higher levels than males. Liver TAG
      content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams
      (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal
      expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF
      diets had lasting effects on body fat and hepatic TAG accumulation in the
      offspring, particularly in females. Whereas the HP diet predisposes to an obese
      phenotype, the maternal HF diet appears to reduce the susceptibility to obesity
      following a high-energy diet challenge in adulthood.

PMID- 23561447
TI  - Progressive cyanosis following Kawashima operation: slow resolution after
      redirection of hepatic veins.
AB  - Progressive cyanosis often develops following Kawashima operation in patients
      with left atrial isomerism, interrupted inferior vena cava and hepatic veins
      draining to the atria. Knowledge on the timing and extend of resolution following
      hepatic venous redirection is sparse. A girl developed progressing cyanosis
      following Kawashima operation at the age of ten months. Arterial oxygen
      saturations at rest dropped to 60-65%. Surgical redirection of hepatic veins into
      the cavopulmonary circulation at the age of three years had no immediate effect.
      However, arterial oxygen saturations increased gradually over nine months to 90
      93% and 95-100% after three years.

PMID- 23561449
TI  - An insight into the public acceptance of nutrigenomic-based personalised
      nutrition.
AB  - It is predicted that non-communicable diseases will account for over 73 % of
      global mortality in 2020. Given that the majority of these deaths occur in
      developed countries such as the UK, and that up to 80 % of chronic disease could
      be prevented through improvements in diet and lifestyle, it is imperative that
      dietary guidelines and disease prevention strategies are reviewed in order to
      improve their efficacy. Since the completion of the human genome project our
      understanding of complex interactions between environmental factors such as diet
      and genes has progressed considerably, as has the potential to individualise
      diets using dietary, phenotypic and genotypic data. Thus, there is an ambition
      for dietary interventions to move away from population-based guidance towards
      'personalised nutrition'. The present paper reviews current evidence for the
      public acceptance of genetic testing and personalised nutrition in disease
      prevention. Health and clear consumer benefits have been identified as key
      motivators in the uptake of genetic testing, with individuals reporting personal
      experience of disease, such as those with specific symptoms, being more willing
      to undergo genetic testing for the purpose of personalised nutrition. This
      greater perceived susceptibility to disease may also improve motivation to change
      behaviour which is a key barrier in the success of any nutrition intervention.
      Several consumer concerns have been identified in the literature which should be
      addressed before the introduction of a nutrigenomic-based personalised nutrition
      service. Future research should focus on the efficacy and implementation of
      nutrigenomic-based personalised nutrition.

PMID- 23561450
TI  - Letter from the editors.

PMID- 23561451
TI  - Guest editorial: IAEA approach to meet nuclear medicine needs of the emerging
      world.

PMID- 23561452
TI  - IAEA programs in empowering the nuclear medicine profession through online
      educational resources.
AB  - The International Atomic Energy Agency's (IAEA) programme in human health aims to
      enhance the capabilities in Member States to address needs related to the
      prevention, diagnosis, and treatment of diseases through the application of
      nuclear techniques. It has the specific mission of fostering the application of
      nuclear medicine techniques as part of the clinical management of certain types
      of diseases. Attuned to the continuous evolution of this specialty as well as to
      the advancement and diversity of methods in delivering capacity building efforts
      in this digital age, the section of nuclear medicine of the IAEA has enhanced its
      program by incorporating online educational resources for nuclear medicine
      professionals into its repertoire of projects to further its commitment in
      addressing the needs of its Member States in the field of nuclear medicine.
      Through online educational resources such as the Human Health Campus website, e
      learning modules, and scheduled interactive webinars, a validation of the
      commitment by the IAEA in addressing the needs of its Member States in the field
      of nuclear medicine is strengthened while utilizing the advanced internet and
      communications technology which is progressively becoming available worldwide.
      The Human Health Campus (www.humanhealth.iaea.org) is the online educational
      resources initiative of the Division of Human Health of the IAEA geared toward
      enhancing professional knowledge of health professionals in radiation medicine
      (nuclear medicine and diagnostic imaging, radiation oncology, and medical
      radiation physics), and nutrition. E-learning modules provide an interactive
      learning environment to its users while providing immediate feedback for each
      task accomplished. Webinars, unlike webcasts, offer the opportunity of enhanced
      interaction with the learners facilitated through slide shows where the presenter
      guides and engages the audience using video and live streaming. This paper
      explores the IAEA's available online educational resources programs geared toward
      the enhancement of the nuclear medicine profession as delivered by the section of
      nuclear medicine of the IAEA.

PMID- 23561453
TI  - Quality management in nuclear medicine for better patient care: the IAEA program.
AB  - The International Atomic Energy Agency promotes the practice of nuclear medicine
      among its Member States with a focus on quality and safety. It considers quality
      culture as a part of the educational process and as a tool to reduce
      heterogeneity in the practice of nuclear medicine, and in turn, patient care.
      Sensitization about quality is incorporated in all its delivery mechanisms. The
      Agency has developed a structured peer-review process called quality management
      (QM) audits in nuclear medicine practices to help nuclear medicine facilities
      improve their quality through this voluntary comprehensive audit process. The
      process is multidisciplinary, covering all aspects of nuclear medicine practice
      with a focus on the patient. It complements other QM and accreditation approaches
      developed by professional societies or accreditation agencies. The Agency is
      committed to propagate its utility and assist in the implementation process.
      Similar auditing programs for practice in diagnostic radiology and radiotherapy,
      called QUADRIL and QUATRO, respectively, are also in place. Necessary amendments
      in the auditing process and content are incorporated based on technological and
      practice changes with time. The reader will become familiar with the approach of
      the Agency on QM in nuclear medicine and its implementation process to improve
      patient care.

PMID- 23561454
TI  - The IAEA technical cooperation programme and nuclear medicine in the developing
      world: objectives, trends, and contributions.
AB  - The International Atomic Energy Agency's technical cooperation (TC) programme
      helps Member States in the developing world with limited infrastructure and human
      resource capacity to harness the potential of nuclear technologies in meeting
      socioeconomic development challenges. As a part of its human health TC
      initiatives, the Agency, through the TC mechanism, has the unique role of
      promoting nuclear medicine applications of fellowships, scientific visits, and
      training courses, via technology procurement, and in the past decade has
      contributed nearly $54 million through 180 projects in supporting technology
      procurement and human resource capacity development among Member States from the
      developing world (low- and middle-income countries). There has been a growing
      demand in nuclear medicine TC, particularly in Africa and ex-Soviet Union States
      where limited infrastructure presently exists, based on cancer and cardiovascular
      disease management projects. African Member States received the greatest
      allocation of TC funds in the past 10 years dedicated to building new or
      rehabilitating obsolete nuclear medicine infrastructure through procurement
      support of single-photon emission computed tomography machines. Agency support in
      Asia and Latin America has emphasized human resource capacity building, as Member
      States in these regions have already acquired positron emission tomography and
      hybrid modalities (positron emission tomography/computed tomography and single
      photon emission computed tomography/computed tomography) in their health systems.
      The strengthening of national nuclear medicine capacities among Member States
      across different regions has enabled stronger regional cooperation among
      developing countries who through the Agency's support and within the framework of
      regional cooperative agreements are sharing expertise and fostering the
      sustainability and productive integration of nuclear medicine within their health
      systems.

PMID- 23561455
TI  - IAEA support to medical physics in nuclear medicine.
AB  - Through its programmatic efforts and its publications, the International Atomic
      Energy Agency (IAEA) has helped define the role and responsibilities of the
      nuclear medicine physicist in the practice of nuclear medicine. This paper
      describes the initiatives that the IAEA has undertaken to support medical physics
      in nuclear medicine. In 1984, the IAEA provided guidance on how to ensure that
      the equipment used for detecting, imaging, and quantifying radioactivity is
      functioning properly (Technical Document [TECDOC]-137, "Quality Control of
      Nuclear Medicine Instruments"). An updated version of IAEA-TECDOC-137 was issued
      in 1991 as IAEA-TECDOC-602, and this included new chapters on scanner-computer
      systems and single-photon emission computed tomography systems. Nuclear medicine
      physics was introduced as a part of a project on radiation imaging and
      radioactivity measurements in the 2002-2003 IAEA biennium program in Dosimetry
      and Medical Radiation Physics. Ten years later, IAEA activities in this field
      have expanded to cover quality assurance (QA) and quality control (QC) of nuclear
      medicine equipment, education and clinical training, professional recognition of
      the role of medical physicists in nuclear medicine physics, and finally, the
      coordination of research and development activities in internal dosimetry. As a
      result of these activities, the IAEA has received numerous requests to support
      the development and implementation of QA or QC programs for radioactivity
      measurements in nuclear medicine in many Member States. During the last 5 years,
      support was provided to 20 Member States through the IAEA's technical cooperation
      programme. The IAEA has also supported education and clinical training of medical
      physicists. This type of support has been essential for the development and
      expansion of the Medical Physics profession, especially in low- and middle-income
      countries. The need for basic as well as specialized clinical training in medical
      physics was identified as a priority for healthcare providers in many countries.
      The IAEA's response to meet the increasing needs for training has been 2-folds.
      Through its regular program, a priority is given to the development of
      standardized syllabi and education and clinical training guides. Through its
      technical cooperation programme, support is given for setting up national medical
      physics education and clinical training programs in countries. In addition,
      fellowships are granted for professionals working in the field for specialized
      training, and workshops are organized at the national and regional level in
      specialized topics of nuclear medicine physics. So as to support on-the-job
      training, the IAEA has also setup a gamma camera laboratory in Seibersdorf,
      Austria. The laboratory is also equipped with QC tools and equipments, and
      radioisotopes are procured when training events are held. About 2-3 specialized
      courses are held every year for medical physicists at the IAEA gamma camera
      laboratory. In the area of research and development, the IAEA supports, through
      its coordinated research projects, new initiatives in quantitative nuclear
      medicine and internal dosimetry. The future of nuclear medicine is driven by
      advances in instrumentation, by the ever increasing availability of computing
      power and data storage, and by the development of new radiopharmaceuticals for
      molecular imaging and therapy. Future developments in nuclear medicine are
      partially driven by, and will influence, nuclear medicine physics and medical
      physics. To summarize, the IAEA has established a number of programs to support
      nuclear medicine physics and will continue to do so through its coordinated
      research activities, education and training in clinical medical physics, and
      through programs and meetings to promote standardization and harmonization of QA
      or QC procedures for imaging and treatment of patients.

PMID- 23561456
TI  - Strengthening radiopharmacy practice in IAEA Member States.
AB  - Radiopharmaceuticals are essential components of nuclear medicine procedures.
      Without radiopharmaceuticals nuclear medicine procedures cannot be performed.
      Therefore it could be said that 'No radiopharmaceutical-no nuclear medicine.' A
      good radiopharmacy practice supports nuclear medicine activities by producing
      radiopharmaceuticals that are safe and are of the required quality in a
      consistent way. As with any medicinal product, radiopharmaceuticals are required
      to be produced under carefully controlled conditions and are tested for their
      quality, prior to the administration to patients, using validated standard
      operating procedures. These procedures are based on the principles of Good
      Manufacturing Practice (GMP). The GMP principles are based on scientific
      knowledge and applicable regulatory requirements and guidance related to
      radiopharmaceutical productions and use. The International Atomic Energy Agency
      (IAEA) is committed to promote, in the Member States (MS), a rational and
      practical approach for the implementation of GMP for compounding or manufacturing
      of diagnostic or therapeutic radiopharmaceuticals. To pursue this goal the IAEA
      has developed various mechanisms and collaborations with individual experts in
      the field and with relevant national and international institutions or
      organizations. IAEA's activities in promoting radiopharmaceutical science include
      commissioning expert advice in the form of publications on radiopharmaceutical
      production, quality control and usage, producing technical guidance on production
      and regulatory aspects related to new radiopharmaceuticals, creating guidance
      documentation for self or internal audits of radiopharmaceutical production
      facilities, producing guidance on implementation of Quality Management System and
      GMP in radiopharmacy, assisting in creation of specific radiopharmaceutical
      monographs for the International Pharmacopoeia, and developing radiopharmacy
      related human resource capabilities in MS through individual and regional
      training courses and education programs. IAEA strongly supports development of
      clinical nuclear medicine services by assisting MS in setting up reliable
      Radiopharmaceutical production facilities for single photon emission computed
      tomography, positron emission tomography, and for therapeutic applications.

PMID- 23561457
TI  - Meeting the challenges of global nuclear medicine technologist training in the
      21st century: the IAEA Distance Assisted Training (DAT) program.
AB  - Many countries have made significant investments in nuclear medicine (NM)
      technology with the acquisition of modern equipment and establishment of
      facilities, however, often appropriate training is not considered as part of
      these investments. Training for NM professionals is continually evolving, with a
      need to meet changing requirements in the workforce. Even places where
      established higher education courses are available, these do not necessarily
      cater to the practical component of training and the ever-changing technology
      that is central to medical imaging. The continuing advances in NM technology and
      growth of applications in quantitative clinical assessment place increases the
      pressure on technologists to learn and practice new techniques. Not only is
      training to understand new concepts limited but often there is inadequate
      training in the basics of NM and this can be a major constraint to the effective
      use of the evolving technology. Developing appropriate training programs for the
      broader international NM community is one of the goals of the International
      Atomic Energy Agency (IAEA). A particularly successful and relevant development
      has been the program on 'distance assisted training (DAT) for NM professionals'.
      The development of DAT was initiated in the 1990s through Australian Government
      funding, administered under auspices of the IAEA through its Regional Cooperative
      Agreement, involving most countries in Asia that are Member States of the IAEA.
      The project has resulted in the development of a set of training modules which
      are designed for use under direct supervision in the workplace, delivered through
      means of distance-learning. The program has undergone several revisions and peer
      reviews with the current version providing a comprehensive training package that
      is now available online. DAT has been utilized widely in Asia or the Pacific
      region, Latin America, and parts of Africa and Europe. Currently there are
      approximately 1000 registered participants, including persons providing student
      support, in the program.

PMID- 23561458
TI  - "Educating the educators" guidelines for education in radiation medicine: a
      pragmatic approach at International Atomic Energy Agency.
AB  - Drawing on the experience of the Division of Human Health within the Department
      of Nuclear Sciences and Applications, we explore "educating the educators"
      guidelines for planning, developing, implementing, and evaluating education and
      training programs in radiation medicine for the International Atomic Energy
      Agency's Member States. The guidelines are based on a pragmatic approach to
      strengthen an internal quality-assurance framework. This article is based on the
      consultants' meetings and reports, participatory observations, bi monthly
      capacity-building sessions, and informal communication with staff members of the
      Division of Human Health, held between December 2009 and August 2012. This
      article contributes to the theoretical and practical applications of "educating
      the educators" philosophy as continuously cultivated in an international
      organization that transforms itself as a learning organization.

PMID- 23561459
TI  - Hybrid imaging worldwide-challenges and opportunities for the developing world: a
      report of a Technical Meeting organized by IAEA.
AB  - The growth in nuclear medicine, in the past decade, is largely due to hybrid
      imaging, specifically single-photon emission tomography-computed tomography
      (SPECT-CT) and positron emission tomography-computed tomography (PET-CT).
      Introduction and use of hybrid imaging has been growing at a fast pace. This has
      led to many challenges and opportunities to the personnel dealing with it. The
      International Atomic Energy Agency (IAEA) keeps a close watch on the trends in
      applications of nuclear techniques in health by many ways, including obtaining
      inputs from member states and professional societies. In 2012, a Technical
      Meeting on trends in hybrid imaging was organized by IAEA to understand the
      current status and trends of hybrid imaging using nuclear techniques, its role in
      clinical practice, and associated educational needs and challenges. Perspective
      of scientific societies and professionals from all the regions of the world was
      obtained. Heterogeneity in value, educational needs, and access was noted and the
      drivers of this heterogeneity were discussed. This article presents the key
      points shared during the technical meeting, focusing primarily on SPECT-CT and
      PET-CT, and shares the action plan for IAEA to deal with heterogeneity as
      suggested by the participants.

PMID- 23561462
TI  - [Screening: from prescription to interpretation in children's obstructive sleep
      apnea syndrome].
AB  - The supply and the demand for sleep recording in children are increasing. With no
      lower age limit, obstructive sleep apnea syndrome can be diagnosed in a lab run
      by a staff trained in conducting and interpreting children's sleep traces
      recorded with an adapted material. Whichever the criteria used to quote
      respiratory events, a relevant diagnosis is performed using both clinical
      presentation and results of sleep traces.

PMID- 23561460
TI  - Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of
      Heparin Induced Thrombocytopenia.
AB  - Heparin Induced Thrombocytopenia (HIT) is caused by antibodies that recognize
      platelet factor 4 (PF4) associated with polyanionic glycosaminoglycan drugs or
      displayed on vascular cell membranes. These antibodies are elicited by
      multimolecular complexes that can occur when heparin is administered in clinical
      settings associated with abundant PF4. Heparin binding alters native PF4 and
      elicits immune recognition and response. While the presence of heparin is
      integral to immunogenesis, the HIT antibody binding site is within PF4. Thus HIT
      antibodies develop and function to cause thrombocytopenia and/or thrombosis only
      in the presence of PF4. Future emphasis on understanding the biology, turnover
      and regulation of PF4 may lead to insights into the prevention and treatment of
      HIT.

PMID- 23561461
TI  - The importance of becoming double-stranded: Innate immunity and the kinetic model
      of HIV-1 central plus strand synthesis.
AB  - Central initiation of plus strand synthesis is a conserved feature of
      lentiviruses and certain other retroelements. This complication of the standard
      reverse transcription mechanism produces a transient "central DNA flap" in the
      viral cDNA, which has been proposed to mediate its subsequent nuclear import.
      This model has assumed that the important feature is the flapped DNA structure
      itself rather than the process that produces it. Recently, an alternative kinetic
      model was proposed. It posits that central plus strand synthesis functions to
      accelerate conversion to the double-stranded state, thereby helping HIV-1 to
      evade single-strand DNA-targeting antiviral restrictions such as APOBEC3
      proteins, and perhaps to avoid innate immune sensor mechanisms. The model is
      consistent with evidence that lentiviruses must often synthesize their cDNAs when
      dNTP concentrations are limiting and with data linking reverse transcription and
      uncoating. There may be additional kinetic advantages for the artificial genomes
      of lentiviral gene therapy vectors.

PMID- 23561463
TI  - Does providing prescription information or services improve medication adherence
      among patients discharged from the emergency department? A randomized controlled
      trial.
AB  - STUDY OBJECTIVE: We determine whether prescription information or services
      improve the medication adherence of emergency department (ED) patients. METHODS:
      Adult patients treated at one of 3 EDs between November 2010 and September 2011
      and prescribed an antibiotic, central nervous system, gastrointestinal, cardiac,
      or respiratory drug at discharge were eligible. Subjects were randomly assigned
      to usual care or one of 3 prescription information or services intervention
      groups: (1) practical services to reduce barriers to prescription filling
      (practical prescription information or services); (2) consumer drug information
      from MedlinePlus (MedlinePlus prescription information or services); or (3) both
      services and information (combination prescription information or services). Self
      reported medication adherence, measured by primary adherence (prescription
      filling) and persistence (receiving medicine as prescribed) rates, was determined
      during a telephone interview 1 week postdischarge. RESULTS: Of the 3,940 subjects
      enrolled and randomly allocated to treatment, 86% (N=3,386) completed the follow
      up interview. Overall, primary adherence was 88% and persistence was 48%. Across
      the sites, primary adherence and persistence did not differ significantly between
      usual care and the prescription information or services groups. However, at site
      C, subjects who received the practical prescription information or services (odds
      ratio [OR]=2.4; 95% confidence interval [CI] 1.4 to 4.3) or combination
      prescription information or services (OR=1.8; 95% CI 1.1 to 3.1) were more likely
      to fill their prescription compared with usual care. Among subjects prescribed a
      drug that treats an underlying condition, subjects who received the practical
      prescription information or services were more likely to fill their prescription
      (OR=1.8; 95% CI 1.0 to 3.1) compared with subjects who received usual care.
      CONCLUSION: Prescription filling and receiving medications as prescribed was not
      meaningfully improved by offering patients patient-centered prescription
      information and services.

PMID- 23561464
TI  - Antibiotic stewardship-what should I do tomorrow?

PMID- 23561466
TI  - The trouble with medication adherence after emergency care.

PMID- 23561465
TI  - Emergency provider analgesic practices and attitudes toward patients with sickle
      cell disease.
AB  - STUDY OBJECTIVE: We determine whether emergency provider attitudes and
      demographics are associated with adherence to national guidelines for the
      management of acute sickle cell disease pain. METHODS: We conducted a cross
      sectional survey of emergency providers at the 2011 annual American College of
      Emergency Physicians Scientific Assembly, using a validated instrument to assess
      provider attitudes and self-reported analgesic practices toward patients with
      sickle cell disease. Multivariable, relative risk regressions were used to
      identify factors associated with adherence to guidelines. RESULTS: There were 722
      eligible participants, with a 93% complete response rate. Most providers self
      reported adherence to the cornerstones of sickle cell disease pain management,
      including parenteral opioids (90%) and redosing opioids within 30 minutes if
      analgesia is inadequate (85%). Self-reported adherence was lower for other
      recommendations, including use of patient-controlled analgesia, acetaminophen,
      non-steroidal anti-inflammatory drugs and hypotonic fluids for euvolemic
      patients. Emergency providers in the highest quartile of negative attitudes were
      20% less likely to redose opioids within 30 minutes for inadequate analgesia
      (risk ratio 0.8; 95% confidence interval [CI] 0.7 to 0.9). High-volume providers
      (those who treat more than 1 sickle cell disease patient per week), were less
      likely to redose opioids within 30 minutes for inadequate analgesia (risk ratio
      0.9; 95% CI 0.8 to 0.9). Pediatric providers were 6.6 times more likely to use
      patient-controlled analgesia for analgesia (95% CI 2.6 to 16.6). CONCLUSION: The
      majority of emergency providers report that they adhere to national guidelines
      about use of opioids for sickle cell disease-related acute pain episodes. Other
      recommendations have less penetration. Negative attitudes toward individuals with
      sickle cell disease are associated with lower adherence to guidelines.

PMID- 23561467
TI  - Impact of interleukin-10, soluble CD25 and interferon-gamma on the prognosis and
      early diagnosis of bacteremic systemic inflammatory response syndrome: a
      prospective observational study.
AB  - INTRODUCTION: The pathophysiology of sepsis consists of two phases. A first phase
      characterized by a substantial increase of pro-inflammatory mediators including
      cytokines and systemic inflammatory markers, and a second phase (immunoparalysis,
      immunodysregulation) associated with the rise of anti-inflammatory mediators. In
      this study we prospectively analyzed 52 consecutive patients with diagnosis of
      systemic inflammatory response syndrome (SIRS) at hospital admission to evaluate
      prognostic and early diagnostic performance of interleukin-10 (IL-10), soluble
      CD25 (sCD25) and interferon-gamma (IFN-gamma) and to confirm the prognostic
      accuracy of the sequential organ failure assessment (SOFA) score. METHODS:
      Patients were divided in two groups (group 1, n=28 patients with bacteremic SIRS
      and group 2, n=24 patients with non-bacteremic SIRS) and then stratified into
      survivors (n=39) and nonsurvivors (n=13). Serum markers were evaluated on the day
      of hospital admission (D-1) and on the 7th day of hospital stay (D-7).
      Concentration of sCD25 was evaluated by a sandwich ELISA kit. Levels of IL-10 and
      IFN-gamma were quantified by a cytokine biochip array by the evidence
      investigator analyzer. Differences between groups were established by the Mann
      Whitney test. Accuracy, sensitivity and specificity of diagnostic markers were
      evaluated by the receiver-operating characteristic curve analysis. Multivariate
      analysis was carried out to evaluate whether studied biomarkers are independent
      predictors of poor outcome in prognosis, and of bacteremic SIRS in diagnosis.
      RESULTS: IL-10, sCD25 and SOFA scores of survivors and nonsurvivors were
      significantly different both at D-1 (P=0.0014; P=0.014 and P=0.0311 respectively)
      and at D-7 (P=0.0002, P=0.014 and P=0.0012 respectively). Between the above
      groups IFN-gamma level was significantly different only at D-7 (P=0.0013).
      Moreover IL-10 and sCD25 were significantly higher in bacteremic versus non
      bacteremic SIRS patients at D-1 and at D-7 (P<0.05). IFN-gamma values showed a
      significant decrease (P<0.05) in patients of group 1 only at D-7. The diagnostic
      accuracy of IL-10 and sCD25 was confirmed by the analysis of the AUROCC at D-1
      and D-7 respectively. Multivariate analysis revealed that sCD25 and IL-10 are
      independent predictors of a poor outcome for our patients during the first day of
      hospital admission. CONCLUSIONS: IL-10 and sCD25 gave a significant contribution
      to prognostic evaluation and early diagnosis of bacteremic SIRS. SOFA score
      appeared to be a reliable prognostic tool in this subset of patients.

PMID- 23561468
TI  - Genomic approaches to chronic lymphocytic leukemia.
AB  - This article discusses recent advances in genomic approaches used to understand
      chronic lymphocytic leukemia. Tools for analyzing DNA-level lesions are
      described, data obtained from these various platforms summarized, and the
      clinical relevance of these findings discussed.

PMID- 23561470
TI  - Understanding the immunodeficiency in chronic lymphocytic leukemia: potential
      clinical implications.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults.
      Although significant advances have been made in the treatment of CLL in the last
      decade, it remains incurable. Treatments may be too toxic for some elderly
      patients, who constitute most of the individuals with this disease, and there
      remain subgroups of patients for which this therapy has minimal activity. This
      article summarizes the current understanding of the immune defects in CLL. It
      also examines the potential clinical implications of these findings.

PMID- 23561471
TI  - The significance of stereotyped B-cell receptors in chronic lymphocytic leukemia.
AB  - Roughly 30% of patients with chronic lymphocytic leukemia (CLL) carry
      immunoglobulin receptors with highly similar primary sequences. Highly similar,
      quasi-identical immunoglobulins are termed stereotyped. Patients with CLL can be
      assigned to different subsets expressing different types of stereotyped
      immunoglobulin receptors. Reliable identification of stereotypy may assist in the
      molecular classification of CLL and thus better-guided, compartmentalized
      research. In several major subsets, stereotypy extends from shared primary
      sequences to shared clinicobiological features and outcome. Reliable
      identification of stereotypy in CLL may pave the way for tailored treatment
      strategies applicable to each major stereotyped subset.

PMID- 23561472
TI  - MBL versus CLL: how important is the distinction?
AB  - Monoclonal B-cell lymphocytosis (MBL) is defined as a clonal B-cell expansion
      whereby the B-cell count is less than 5 * 10(9)/L and no symptoms or signs of
      lymphoproliferative disorders are detected. Based on B-cell count, MBL is further
      divided into low-count and clinical MBL. While low-count MBL seems to carry
      relevance mostly from an immunological perspective, clinical MBL and chronic
      lymphocytic leukemia appear to be overlapping entities. Only a deeper knowledge
      of molecular pathways and microenvironmental influences involved in disease
      evolution will help to solve the main clinical issue, i.e. how to differentiate
      nonprogressive and progressive cases requiring intensive follow-up.

PMID- 23561473
TI  - The role of minimal residual disease measurements in the therapy for CLL: is it
      ready for prime time?
AB  - With the advent of multiple highly effective treatment options, minimal residual
      disease (MRD) measurements gained interest as a prognostic marker in chronic
      lymphocytic leukemia. This article provides a model explaining the clinical
      significance of MRD in different clinical situations and reviews available data
      to support that model. Factors with a possible impact on the clinical
      significance of MRD are discussed: technique for MRD quantification, treatment
      regimen, clinical response, time-point for sampling, and the additional impact of
      molecular risk features. Also described are data supporting the use of MRD
      assessments as a surrogate end-point in randomized clinical trials.

PMID- 23561469
TI  - Biology of chronic lymphocytic leukemia in different microenvironments: clinical
      and therapeutic implications.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature
      monoclonal B cells in peripheral blood, bone marrow, spleen, and lymph nodes. The
      trafficking, survival, and proliferation of CLL cells is tightly regulated by the
      surrounding tissue microenvironment and is mediated by antigenic stimulation,
      close interaction with various accessory cells and exposure to different
      cytokines, chemokines, and extracellular matrix components. In the last decade
      there have been major advances in the understanding of the reciprocal
      interactions between CLL cells and the various microenvironmental compartments.
      This article discusses the role of the microenvironment in the context of efforts
      to develop novel therapeutics that target the biology of CLL.

PMID- 23561474
TI  - 17p deletion in chronic lymphocytic leukemia: risk stratification and therapeutic
      approach.
AB  - Treatment of chronic lymphocytic leukemia has greatly advanced in the past few
      years since introduction of the fludarabine/cyclosphosphamide/rituximab regimen
      as first-line therapy. Nevertheless, 17p deletion represents a challenge because
      conventional treatment does not provide satisfactory results. 17p deletion and
      TP53 mutation are the major factors accounting for rapid disease progression,
      poor response to therapy, early relapse, and short survival. Allogeneic stem cell
      transplantation harbors curative potential but also considerable morbidity and
      mortality. Novel agents acting independently of the p53 signaling pathway, with
      favorable side-effect profiles, are promising. This review summarizes up-to-date
      knowledge about 17p deletion and the spectrum of treatment options.

PMID- 23561475
TI  - Improving the treatment outcome of patients with chronic lymphocytic leukemia
      through targeted antibody therapy.
AB  - Therapy for chronic lymphocytic leukemia (CLL) has evolved dramatically
      throughout the years. In 1997, rituximab (Rituxan), a CD20 monoclonal antibody
      (mAb), became the first mAb approved by the Food and Drug Administration for
      marketing in the treatment of cancer, specifically targeting B-cell malignancies.
      Over the last 10 years, rituximab or other mAbs including alemtuzumab and
      ofatumumab have become an integral part of the standard of care for CLL patients
      as single agents or in combination with chemotherapy or other immunotherapy. This
      review discusses the currently approved and novel mAbs for the treatment of CLL.

PMID- 23561476
TI  - Phosphoinositide 3'-kinase inhibition in chronic lymphocytic leukemia.
AB  - Phosphoinositide 3'-kinase (PI3K) is a key node in the B-cell receptor pathway,
      which plays a crucial role in the trafficking, survival, and proliferation of
      chronic lymphocytic leukemia (CLL) cells. This article reviews the biology of
      PI3K, focusing on its relationship to the CLL microenvironment, and discusses the
      biological rationale for PI3K inhibition in CLL. Preliminary safety and efficacy
      data from early phase clinical trials is also discussed. Potential biomarkers for
      clinical response to PI3K inhibitors such as ZAP-70, IGHV status, and CCL3 are
      examined. Where PI3K inhibition may fit in the evolving landscape of CLL therapy
      is also explored.

PMID- 23561478
TI  - The evolving role of stem cell transplantation in chronic lymphocytic leukemia.
AB  - This article describes the current role and perspectives of "new" allogeneic stem
      cell transplantation (alloSCT) in the treatment of chronic lymphocytic leukemia
      (CLL). Clinical trials and minimal residual disease (MRD) studies provide clear
      evidence that graft-versus-leukemia activity is working in CLL and can provide
      long-term MRD-free survival in up to 50% of patients undergoing alloSCT. AlloSCT
      is effective also in poor-risk CLL as defined by the European Group for Blood and
      Marrow Transplantation transplant consensus. Novel forms of (reduced intensity)
      conditioning have resulted in dramatic reduction of early morbidity and mortality
      of alloSCT in CLL.

PMID- 23561477
TI  - Chimeric antigen receptor therapy for chronic lymphocytic leukemia: what are the
      challenges?
AB  - Chimeric antigen receptor (CAR)-modified T cells targeting CD19 expressed by
      normal and malignant B cells is a unique therapy for patients with chronic
      lymphocytic leukemia (CLL); recent results highlight the potential of this
      therapy for patients with relapsed CLL. Because adoptive transfer of CAR-modified
      T cells is a novel approach, there are issues for the medical oncologist to
      consider when evaluating current and future clinical trials for CLL patients.
      This article reviews the impact of CAR design, T-cell production, T-cell dose,
      conditioning regimens, and tumor burden at the time of CAR-modified T-cell
      infusion on the efficacy of this therapy.

PMID- 23561479
TI  - Hematology/Oncology Clinics of North America. Chronic Lymphocytic Leukemia.
      Preface.

PMID- 23561480
TI  - Efficacy of debridement and wound cleansing with 2% hydrogen peroxide on graft
      take in the chronic-colonized burn wounds; a randomized controlled clinical
      trial.
AB  - BACKGROUND: Severe burns are associated with dramatic outcomes which are
      potentially detrimental. Nowadays the standard treatment for deep partial
      thickness and full-thickness burn is early excision and grafting, which is not
      always feasible this leads to chronicity and microbial colonization of burn
      wounds. Interesting properties of hydrogen peroxide 2% soaked gauze convinced us
      to use it in management of chronic burn wounds. METHODS: From January 2009 to
      September 2011, in a prospective clinical trial, 49 patients (98 limbs) with
      chronic-colonized burn wounds in both limbs were included in this study. Tissue
      cultures were taken from all the wounds. For the right, after debridement of
      granulation tissue and washing with hydrogen peroxide 2% soaked gauze for 5min
      followed by normal saline irrigation, grafting was done; debridement and skin
      grafting was performed in the conventional method in left limb wounds. The
      success rate of graft take was compared between two groups, after 21 days by the
      surgeon using the formula: Graft take surface area (cm2) x 100%/Total grafted
      area (cm2). RESULTS: The study group was composed of 98 limbs in 49 patients with
      mean age of 26.44+/-5.66 and burn in 28.3+/-7.23% TBSA. The most common causes of
      the burn wounds chronicity was delayed admission associated with poor compliance.
      (44.8%) Staphylococcus was the most frequent isolate bacterial wounds
      colonization in our patients. (59.2%) Mean graft take was 82.85% in right limbs,
      and 65.61% in left limbs; which was significantly different (P<0.05).
      CONCLUSIONS: Our study showed that, administration of hydrogen peroxide
      intraoperatively appears to be safe and significantly increases the mean success
      rate graft take in chronic-colonized wounds. Therefore, it can be recommended in
      management of chronic burn wounds management.

PMID- 23561481
TI  - Tetrandrine ameliorates cognitive impairment via inhibiting astrocyte-derived
      S100B activation in a rat model of chronic cerebral hypoperfusion.
AB  - OBJECTIVES: To investigate the effects of tetrandrine (Tet) on cognitive
      impairment induced by chronic cerebral hypoperfusion and its potential anti
      inflammatory mechanism by modulating the expression of S100B, interleukin-1 beta
      (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide
      synthase (iNOS). METHODS: Chronic cerebral hypoperfusion was induced by ligation
      of the bilateral common carotid arteries for 8 weeks. Rats were treated with Tet
      (10 mg/kg or 30 mg/kg) intraperitoneally every 3 days for 4 weeks. Cognitive
      function of rats was evaluated by the Morris water maze. Hematoxylin eosin (H &
      E) and Nissl staining were used to observe neuronal damage in the hippocampal CA1
      region. Immunofluorescence, quantitative real-time polymerase chain reaction (QT
      PCR), and western blot were performed to measure S100B, IL-1 beta, TNF-alpha, and
      iNOS levels in the CA1 region of chronic cerebral hypoperfusion rats. RESULTS:
      The Tet-treated group significantly decreased the escape latency of chronic
      cerebral hypoperfusion rats in finding the hidden platform (P <0.05). Compared
      with the 2-VO (two-vessel occlusion) group, more neurons with regular morphology
      and/or Nissl bodies in the hippocampus were observed in the Tet-treated group,
      suggesting attenuated neuronal damage and degeneration. Additionally, S100B, IL-1
      beta, TNF-alpha, and iNOS levels were significantly (P <0.05) decreased in the
      CA1 region of the chronic cerebral hypoperfusion affected rats treated with Tet.
      CONCLUSION: Our results found that Tet could improve cognitive impairment in the
      chronic cerebral hypoperfusion rats. Tetrandrine may be a novel and promising
      candidate for future treatment and/or prevention of chronic cerebral
      hypoperfusion via inhibiting S100B activation and decreasing the expression of IL
      1 beta, TNF-alpha, and iNOS in the hippocampal CA1 region.

PMID- 23561482
TI  - Cyclic loading biomechanical analysis of the pullout strengths of rotator cuff
      and glenoid anchors: 2013 update.
AB  - PURPOSE: The purpose of this study was to evaluate the biomechanical and design
      characteristics of newer suture anchors under cyclic loading. METHODS: Suture
      anchors were tested in fresh porcine cortical and cancellous bone by cyclic
      loading (10 to 100 N for 200 cycles) followed by destructive testing parallel to
      the insertion axis at 12.5 mm per second. End points included ultimate failure
      load, displacement at 100 and 200 cycles, failure mode, and stiffness. Anchors
      tested included ReelX (Stryker Endoscopy, San Jose, CA); Footprint Ultra PK (4.5
      and 5.5 mm) (Smith & Nephew, Andover, MA); TwinFix (4.5, 5.5, and 6.5 mm made
      from polyether ether ketone [PEEK], hydroxyapatite [HA], and titanium [Ti])
      (Smith & Nephew Endoscopy, Andover, MA); Morphix (2.5 and 5.5 mm) (MedShape
      Solutions, Atlanta, GA); CrossFT BC (ConMed-Linvatec, Largo, FL); JuggerKnot (1.5
      and 2.8 mm) (Biomet Sports Medicine, Warsaw, IN); Healicoil (Smith & Nephew
      Endoscopy, Andover, MA); Quattro (X, Link, and GL) (Cayenne Medical, Scottsdale,
      AZ); Healix (Biocryl Rapide [BR], PEEK, and Ti) (DePuy Mitek, Raynham, MA); Twin
      Loop (3.5 mm, PEEK) (Stryker Endoscopy, San Jose, CA); PressFT (2.1 and 2.6 mm)
      (ConMed Linvatec, Largo FL); Y-Knot (ConMed Linvatec, Largo FL); Gryphon (BR and
      PEEK) (DePuy Mitek, Raynham, MA); and Iconix (1, 2, and 3) (Stryker Endoscopy,
      San Jose, CA). RESULTS: Rotator cuff anchors showed greater failure loads than
      did glenoid anchors in metaphyseal bone (rotator cuff anchors 448 N v glenoid
      anchors 296 N) (P = .001) and cancellous bone (rotator cuff anchors 435 N v
      glenoid anchors 225 N) (P < .001). No anchors reached 5 mm of displacement during
      cyclic loading. TwinFix anchors showed greater displacement at 100 (P = .014) and
      200 cycles (P = .036) than did other rotator cuff anchors, although the ReelX and
      Morphix showed the greatest displacements. Rotator cuff anchors failed
      principally by eyelet breaking, whereas glenoid anchors failed more often by
      anchor pullout than by any other mode. No differences in stiffness were observed
      across the different rotator cuff and glenoid anchors tested. CONCLUSIONS:
      Rotator cuff anchors showed higher failure strengths than did glenoid anchors,
      regardless of bone type. TwinFix anchors showed more cyclic displacement than did
      other rotator cuff anchors (except the ReelX and Morphix anchors) and the glenoid
      anchors tested. The failure mode was dependent on the specific anchor. CLINICAL
      RELEVANCE: Suture anchor constructs tested showed that failure load is dependent
      on anchor type (rotator cuff anchor or glenoid anchor) but not on anchor location
      (cancellous or cortical bone).

PMID- 23561483
TI  - Long-term outcome for arthroscopic repair of partial articular-sided
      supraspinatus tendon avulsion.
AB  - PURPOSE: To assess the long-term clinical outcome of arthroscopic transtendon
      repair of partial articular-sided supraspinatus tendon avulsion (PASTA) lesions
      using University of California, Los Angeles (UCLA) and Short Form 36 (SF-36)
      scores. METHODS: We prospectively collected and retrospectively reviewed data on
      15 patients who underwent arthroscopic transtendon PASTA repair between 1997 to
      2001. The mean patient age was 50.4 years (range, 31 to 68 years). Mean follow-up
      was 13.5 years (range, 12 to 15 years). To determine clinical outcome, UCLA and
      SF-36 scores were obtained preoperatively, at 1 to 3 years postoperatively, and
      again at final postoperative evaluation. RESULTS: Of the 15 patients enrolled in
      this study, 13 underwent concomitant procedures, including 10 subacromial
      decompressions, 2 open and one arthroscopic biceps tenodesis, 2 SLAP repairs, and
      one Bankart repair. There were no complications. A revision rotator cuff repair
      was performed 8 years after the index procedure in one patient (7%), indicating a
      93% long-term success rate for arthroscopic PASTA repair. A significant
      difference (P < .0001) was noted between preoperative and postoperative UCLA
      scores. Pain and shoulder function improved in all patients. SF-36 scores showed
      improvement in physical health, physical functioning, and bodily pain (P = .003,
      P = .005, and P = .005, respectively). All 15 patients were satisfied with the
      surgery. CONCLUSIONS: Long-term follow-up shows that arthroscopic transtendon
      PASTA repair provides reliable and sustained pain relief and improvement in
      shoulder function. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 23561484
TI  - Mixed states in DSM-5: implications for clinical care, education, and research.
AB  - The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision (DSM-IV-TR) nomenclature for the co-occurrence of manic and depressive
      symptoms (mixed states) has been revised in the new DSM-5 version to accommodate
      a mixed categorical-dimensional concept. The new classification will capture
      subthreshold non-overlapping symptoms of the opposite pole using a "with mixed
      features" specifier to be applied to manic episodes in bipolar disorder I (BD I),
      hypomanic, and major depressive episodes experienced in BD I, BD II, bipolar
      disorder not otherwise specified, and major depressive disorder. The revision
      will have a substantial impact in several fields: epidemiology, diagnosis,
      treatment, research, education, and regulations. The new concept is data-driven
      and overcomes the problems derived from the extremely narrow definition in the
      DSM-IV-TR. However, it is unclear how clinicians will deal with the possibility
      of diagnosing major depression with mixed features and how this may impact the
      bipolar-unipolar dichotomy and diagnostic reliability. Clinical trials may also
      need to address treatment effects according to the presence or absence of mixed
      features. The medications that are effective in treating mixed episodes per the
      DSM-IV-TR definition may also be effective in treating mixed features per the DSM
      5, but new studies are needed to demonstrate it.

PMID- 23561485
TI  - Behavioural effects of compounds co-consumed in dietary forms of caffeinated
      plants.
AB  - Research into the cognitive and mood effects of caffeine in human subjects has
      highlighted some fairly robust and well-accepted effects. However, the majority
      of these studies have focused on caffeine in isolation; whilst caffeine is
      normally consumed in the form of plant-derived products and extracts that
      invariably contain other potentially bioactive phytochemicals. The aim of the
      present review is to consider the possible mechanisms of action of co-occurring
      phytochemicals, and any epidemiological evidence suggesting that they contribute
      to potential health benefits ascribed to caffeine. Intervention studies to date
      that have been conducted to explore the effects on brain function of the non
      caffeine components in caffeine-bearing plants (coffee, tea, cocoa, guarana),
      either alone or in combination with caffeine, will also be summarised. Research
      is beginning to accumulate showing independent effects for several of the
      phytochemicals that co-occur with caffeine, and/or a modulation of the effects of
      caffeine when it is co-consumed with these naturally concomitant phytochemicals.
      The present review highlights that more research aimed at understanding the
      effects of these compounds is needed and, more importantly, the synergistic
      relationship that they may have with caffeine.

PMID- 23561486
TI  - Stochastic patterns of polymorphism after a selective sweep over a subdivided
      population.
AB  - The geographic structure of a population, which is modelled as a network of
      several small random-mating populations or demes exchanging migrants between
      them, limits the rapid spread of a beneficial allele under strong directional
      selection to the entire population. This weakens or modifies the hitchhiking
      effect of the beneficial allele on the pattern of genetic variation at linked
      neutral loci. Previous studies suggested that the characteristic patterns of
      polymorphism arise with selective sweeps in such a subdivided population.
      However, they did not fully address the stochastic pattern, as expected in an
      actual sample of DNA sequence, of such patterns. This study uses a novel method
      of individual-based forward-in-time simulation to generate multi-locus neutral
      polymorphism after a selective sweep in a moderately subdivided population.
      Population subdivision is shown to cause frequency spectrum to shift slightly
      such that Tajima's D becomes less negative than expected under a panmictic
      population. Similarly, the pattern of linkage disequilibrium showed very small
      change due to population subdivision. On the other hand, the value of Wright's F
      ST at closely linked neutral loci relative to that at unlinked loci greatly
      increased by population subdivision as predicted by previous studies. Finally,
      the distribution of the gradient of heterozygosity along the migration path of
      beneficial mutation, previously suggested to allow the inference of the direction
      of spread, was investigated. The variance of difference in heterozygosity was
      much larger than the mean, suggesting that such an inference may not be
      practical.

PMID- 23561487
TI  - Mutational spectrum of the APC and MUTYH genes and genotype-phenotype
      correlations in Brazilian FAP, AFAP, and MAP patients.
AB  - BACKGROUND: Patients with multiple colorectal adenomas are currently screened for
      germline mutations in two genes, APC and MUTYH. APC-mutated patients present
      classic or attenuated familial adenomatous polyposis (FAP/AFAP), while patients
      carrying biallelic MUTYH mutations exhibit MUTYH-associated polyposis (MAP). The
      spectrum of mutations as well as the genotype-phenotype correlations in polyposis
      syndromes present clinical impact and can be population specific, making
      important to obtain genetic and clinical data from different populations.
      METHODS: DNA sequencing of the complete coding region of the APC and MUTYH genes
      was performed in 23 unrelated Brazilian polyposis patients. In addition, mutation
      negative patients were screened for large genomic rearrangements by multiplex
      ligation-dependent probe amplification, array-comparative genomic hybridization,
      and duplex quantitative PCR. Biallelic MUTYH mutations were confirmed by allele
      specific PCR. Clinical data of the index cases and their affected relatives were
      used to assess genotype-phenotype correlations. RESULTS: Pathogenic mutations
      were identified in 20 of the 23 probands (87%): 14 in the APC gene and six in the
      MUTYH gene; six of them (30%) were described for the first time in this series.
      Genotype-phenotype correlations revealed divergent results compared with those
      described in other studies, particularly regarding the extent of polyposis and
      the occurrence of desmoid tumors in families with mutations before codon 1444
      (6/8 families with desmoid). CONCLUSIONS: This first comprehensive investigation
      of the APC and MUTYH mutation spectrum in Brazilian polyposis patients showed a
      high detection rate and identified novel pathogenic mutations. Notably, a
      significant number of APC-positive families were not consistent with the
      predicted genotype-phenotype correlations from other populations.

PMID- 23561488
TI  - Discovering human immunodeficiency virus mutational pathways using temporal
      Bayesian networks.
AB  - OBJECTIVE: The human immunodeficiency virus (HIV) is one of the fastest evolving
      organisms in the planet. Its remarkable variation capability makes HIV able to
      escape from multiple evolutionary forces naturally or artificially acting on it,
      through the development and selection of adaptive mutations. Although most drug
      resistance mutations have been well identified, the dynamics and temporal
      patterns of appearance of these mutations can still be further explored. The use
      of models to predict mutational pathways as well as temporal patterns of
      appearance of adaptive mutations could greatly benefit clinical management of
      individuals under antiretroviral therapy. METHODS AND MATERIAL: We apply a
      temporal nodes Bayesian network (TNBN) model to data extracted from the Stanford
      HIV drug resistance database in order to explore the probabilistic relationships
      between drug resistance mutations and antiretroviral drugs unveiling possible
      mutational pathways and establishing their probabilistic-temporal sequence of
      appearance. RESULTS: In a first experiment, we compared the TNBN approach with
      other models such as static Bayesian networks, dynamic Bayesian networks and
      association rules. TNBN achieved a 64.2% sparser structure over the static
      network. In a second experiment, the TNBN model was applied to a dataset
      associating antiretroviral drugs with mutations developed under different
      antiretroviral regimes. The learned models captured previously described
      mutational pathways and associations between antiretroviral drugs and drug
      resistance mutations. Predictive accuracy reached 90.5%. CONCLUSION: Our results
      suggest possible applications of TNBN for studying drug-mutation and mutation
      mutation networks in the context of antiretroviral therapy, with direct impact on
      the clinical management of patients under antiretroviral therapy. This opens new
      horizons for predicting HIV mutational pathways in immune selection with
      relevance for antiretroviral drug development and therapy plan.

PMID- 23561489
TI  - Myosin Vb gene is associated with schizophrenia in Chinese Han population.
AB  - Myosin Vb (MYO5B) has recently been implicated in the etiology of bipolar
      disorder in a genome-wide association study (GWAS). This gene is involved in
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit
      glutamate receptor 1 (GluR1) recycling and plays an important role in the primary
      excitatory neurotransmission. Dysfunction of the brain glutamate system has been
      postulated to be involved in the pathophysiology in schizophrenia. To further
      investigate the association between MYO5B polymorphisms and schizophrenia, we
      genotyped nine single nucleotide polymorphisms (SNPs) in an independent sample of
      1463 individuals with schizophrenia and 1563 healthy control subjects, and
      detected three SNPs and two haplotype blocks which displayed significant
      association with schizophrenia. This association was further strengthened by the
      results of meta-analysis. Our data strongly supported that the MYO5B gene might
      be associated with schizophrenia in the Chinese Han population and they have
      implications for understanding the glutamate hypothesis of schizophrenia.

PMID- 23561490
TI  - Stigma and perception of psychological distress and depression in Australian
      trained medical students: results from an inter-state medical school survey.
AB  - Stigmatisation towards depression has previously been reported amongst medical
      students from a variety of backgrounds. This study explored personal and
      perceived stigmas associated with depression, and their relationship with
      demographics, knowledge of depression, levels of personal stress and history of
      medical illness amongst Australian-trained medical students. A cross-sectional
      survey was undertaken amongst students enroled June-to-August 2009 across four
      Australian medical schools. In total, 1010 students completed the survey, a
      response rate of 29.6%. Approximately 25% of students reported a past history of
      depression. Higher stress (K-10 scores) was reported by females and those with a
      past history of depression. On a scale of 0-to-5, the mean (+/-S.D.) personal and
      perceived stigma depression scores were 1.83+/-1.49 and 4.05+/-1.42 respectively.
      In multivariate analysis, higher perceived stigma and K-10 scores, a past history
      of anxiety and Year 3 of medical school indicated higher personal stigma scores.
      Perceived stigma was positively associated with K-10 scores, personal stigma
      scores, and a Caucasian background. Our findings suggest a high level of personal
      and particularly perceived stigma associated with depression amongst medical
      students, especially those displaying higher levels of stress. Adequate support
      and screening for psychological stress may de-stigmatise depression and improve
      mental health amongst future Australian doctors. 

PMID- 23561491
TI  - Determination of natural radioactivity by gross alpha and beta measurements in
      ground water samples.
AB  - In this study, the activity concentrations of the gross alpha and beta in ground
      water samples collected from the different drilled wells in Nevsehir province
      were measured to assess annual effective dose due to the ingestion of the water
      samples. Nevsehir province is one of the major cities of Cappadocia Region which
      is a popular tourist destination as it has many areas with unique geological,
      historic, and cultural features. Sampling and measurements were carried out in
      the autumn of 2011 and the spring of 2012. The values of the activity
      concentrations of the gross alpha and beta measured in the water samples ranged
      from 80 to 380 mBq L(-1) with a mean of 192 mBq L(-1) and 120-3470 mBq L(-1) with
      a mean of 579 mBq L(-1) respectively. All values of the gross alpha were lower
      than the limit value of 500 mBq L(-1) while two ground water samples were found
      to have gross beta activity concentrations of greater than 1000 mBq L(-1).
      Therefore two water samples were the subject of further radioisotope-specific
      analysis. The obtained result indicated that the elevated activity concentrations
      of the gross beta in these water samples are dominated by (40)K activity. Annual
      effective doses ranged from 0.04 to 0.20 mSv y(-1).

PMID- 23561492
TI  - Formation of iodinated disinfection by-products during oxidation of iodide
      containing waters with chlorine dioxide.
AB  - This study was to explore the formation of iodinated disinfection by-products (I
      DBPs), including iodoform (CHI3), iodoacetic acid (IAA) and triiodoacetic acid
      (TIAA), when iodide-containing artificial synthesized waters and raw waters are
      in contact with chlorine dioxide (ClO2). Among the investigated I-DBPs, CHI3 was
      the major species during ClO2 oxidation in artificial synthesized waters. Impact
      factors were evaluated, including the concentrations of ClO2, iodide (I(-)),
      dissolved organic carbon (DOC) and pH. Formation of CHI3, IAA and TIAA followed
      an increasing and then decreasing pattern with increased ClO2 or DOC
      concentration. I-DBPs yield was significantly affected by solution pH. High
      concentrations of I-DBPs were generated under circumneutral conditions with the
      maximum formation at pH 8. The increase of I(-) concentration can increase I-DBPs
      yields, but the increment was suppressed when I(-) concentration was higher than
      50 MUM. When 100 MUg/L I(-)and ClO2 (7.5-44.4 MUM) were spiked to the raw water
      samples from Yangshupu and Minhang drinking water treatment plant, certain
      amounts of CHI3 and IAA were found under pH 7 and the concentrations were
      strongly correlated with ClO2 dosage and water qualities, however, no TIAA was
      detected. Finally, we investigated I-DBPs formation of 18 model compounds,
      including 4 carboxylic acids, 5 phenols and 8 amino acids, treating with ClO2
      when I(-) was present. Results showed that most of these model compounds could
      form a considerable amount of I-DBPs, especially for propanoic acid, butanoic
      acid, resorcinol, hydroquinone, alanine, glutamic acid, phenylalanine and serine.

PMID- 23561493
TI  - Substance flow analysis as a tool for mitigating the impact of pharmaceuticals on
      the aquatic system.
AB  - Pharmaceuticals constitute an important environmental issue for receiving waters.
      A holistic approach, taking into consideration the sources of these compounds
      (hospitals, domestic use), discharges (wastewater effluent, combined sewer
      overflows) and related risks to the environment, is therefore needed to develop
      the best protection strategy. The substance flow analysis (SFA) approach,
      applied, for example, to the city of Lausanne, Switzerland, is an ideal tool to
      tackle these issues. Four substances were considered: one antibiotic
      (ciprofloxacin), an analgesic (diclofenac), and two anti-epileptics
      (carbamazepine and gabapentin). Consumption data for the main hospital of the
      city (916 beds) and for the population were available. Micropollutant
      concentrations were measured at different points of the system: wastewater inlet
      and outlet (WWTP), combined sewer overflows (CSO) and in the receiving waters
      (Vidy Bay, Lake Geneva). Measured and predicted concentrations were in agreement,
      except for diclofenac, for which analytical uncertainties were expected. Seven
      different scenarios were considered (supplementary treatment at the WWTP, at the
      hospital or at both places, etc.). Based on the results obtained, the
      supplementary treatment at the WWTP decreases the load of pharmaceuticals
      reaching surface water by a factor between 2 and 27, depending on the compound
      and on the technique. The treatment at the hospitals only influences the amount
      of ciprofloxacin reaching the environment and decreases the release by one third.
      The contribution of CSO to surface water pollution is low compared to that of the
      WWTP for the selected compounds. Regarding the risk for the receiving waters,
      ciprofloxacin was found to be the most problematic compound, with a risk quotient
      far above 1. In this particular case, a treatment at the WWTP is not sufficient
      to reduce the risk, and additional measures at the CSO or at the hospital should
      be considered. SFA is an ideal tool for developing the best strategy for
      pharmaceutical elimination, but its application depends on data availability and
      local conditions.

PMID- 23561494
TI  - Chronic impact of tetracycline on the biodegradation of an organic substrate
      mixture under anaerobic conditions.
AB  - The study evaluates the chronic impact of the antibiotic tetracycline on the
      biodegradation of organic substrate under anaerobic conditions. The experiments
      involved an anaerobic sequencing batch reactor fed with a synthetic substrate
      mixture including glucose, starch and volatile fatty acids, and operated in a
      sequence of different phases with gradually increasing tetracycline doses of 1.65
      8.5 mg/L, for more than five months. Tetracycline exerted a terminal/lethal
      effect at 8.5 mg/L on the microbial community under anaerobic conditions, which
      caused the inhibition of substrate/COD utilization and biogas generation and
      leading to a total collapse of the reactor. The microbial activity could not be
      recovered and re-started within a period of more than 10 days, even after
      stopping tetracycline dosing. At lower doses, substrate utilization was not
      affected but a reduction of 10-20% was observed in the biogas/methane generation,
      suggesting that substrate utilization of tetracycline to the biomass was limiting
      their bioavailability. During the experiments, tetracycline was partially removed
      either through biodegradation or conversion into its by-products. The adverse
      long-term impact was quite variable for fermenting heterotrophic and methanogenic
      fractions of the microbial community based on changes inflicted on the
      composition of remaining/residual organic substrate.

PMID- 23561495
TI  - Direct observation of bacterial deposition on and detachment from nanocomposite
      membranes embedded with silver nanoparticles.
AB  - A microscope-equipped online monitoring system was used to investigate the
      bacterial deposition and detachment kinetics of a nanocomposite membrane that was
      synthesized by embedding silver nanoparticles in a polysulfone membrane. A pure
      polysulfone membrane was used as a control in the experiments. The deposition
      experiments with live bacteria showed that the bacterial deposition rates were
      the same for the nanocomposite and control polysulfone membranes. After the
      rinsing experiments, however, on average a high bacterial detachment ratio of 75%
      was observed for the nanocomposite membrane, compared with 18% for the control
      polysulfone membrane. These results indicate that the presence of silver
      nanoparticles as an antibacterial agent enhances the antiadhesive property of the
      nanocomposite membrane by decreasing the capability of bacteria in permanently
      attaching to the membrane surface. A quartz crystal microbalance with dissipation
      was used to study silver leaching. It was found that silver leaching
      significantly decreased within the first few hours. Deposition and rinsing
      experiments with dead bacterial cells revealed that the dead cell deposition
      rates were similar for both membranes, and so were the detachment ratios. Since
      the nanocomposite membrane did not show any antiadhesive action against dead
      cells, its antiadhesive property was most likely attributed to its ability to
      inhibit biological activities. Results of the antibacterial experiments confirmed
      that the nanocomposite membrane was highly effective in inhibiting bacterial
      growth with an antibacterial efficiency of over 98%, which did not decrease even
      after the membrane was soaked in DI water for seven days.

PMID- 23561496
TI  - Bioavailability of organic phosphorus to Pseudokirchneriella subcapitata as
      affected by phosphorus starvation: an isotope dilution study.
AB  - Phosphorus (P) starved algae have a capacity to rapidly take up P when resupplied
      to P. This study was set-up to measure to what extent P starvation enhances the
      potential of algae to utilize organic P forms. The initial (<0.5 h) PO4 uptake
      rates of cells of Pseudokirchneriella subcapitata increased up to 18-fold with
      increasing starvation. Algae from different levels of P starvation were
      subsequently exposed to different model organic P forms and carrier-free (33)PO4.
      Uptake (1h) of P from organic P-increased up to 5-fold with increasing P
      starvation. The bioavailability of organic P, relative to PO4, was calculated
      from uptake of (31)P and (33)P isotopes assuming no isotopic exchange with
      organic P-forms. This relative bioavailability ranged from 0 to 57% and remained
      generally unaffected by the extent of P-starvation. This result was found for
      cells that were either or not treated by a wash method to remove extracellular
      phosphatases. Short-term P uptake rate sharply increases with decreasing internal
      P content of the algal cells but the bioavailability of organic P, relative to
      PO4, is not enhanced. Such finding suggests that P-starvation enhances PO4 uptake
      capacity and organic P hydrolysis capacity to about the same extent.

PMID- 23561497
TI  - Flocculation performance and mechanism of graphene oxide for removal of various
      contaminants from water.
AB  - The application of nanomaterials in water treatment plants has attracted
      significant attention recently. This study investigates the possibility of using
      graphene oxide (GO) as a novel flocculant to remove contaminants with different
      surface charges from water, including two particulate ones (kaolin and hematite)
      and two soluble ones (humic acid (HA) and cationic light yellow 7GL dye (7GL)).
      The flocculation performances of traditional polyaluminum chloride (PAC) and
      original graphite were also tested for comparison. Fractal theory was applied to
      evaluate the floc properties and explore the flocculation mechanism in
      combination with zeta potential measurements. For negatively charged
      contaminants, kaolin and HA, GO was observed to remove these contaminants
      successfully via the sweeping flocculation effect under acidic and neutral
      conditions. However, GO was less efficient than PAC. For positively charged
      contaminants, hematite and 7GL, the flocculation performances of GO were
      significantly improved than those of PAC via patching effect for hematite
      suspension and charge neutralization effect for 7GL solution. The results
      highlighted the extensive potential applicability of GO as a suitable flocculant
      in water treatment.

PMID- 23561498
TI  - N2O and NO emissions from a partial nitrification sequencing batch reactor:
      exploring dynamics, sources and minimization mechanisms.
AB  - A sequencing batch reactor (SBR) was enriched with ammonia oxidizing bacteria
      (AOB) in order to treat synthetic reject wastewater (1 g NH4+ N/L). Partial
      nitrification was successfully achieved at a NH4+ -N to NO2- -N conversion rate
      of 98%. The emission dynamics of nitrous oxide (N2O) and nitric oxide (NO) were
      monitored during normal operation and under 3 different cycle configurations. An
      N2O peak was detected during the first 5 min of the cycle in all cases which
      corresponded to 60-80% of the total N2O emitted. When anoxic phases were
      introduced, N2O emissions were minimized but NO increased. Factors affecting the
      initial N2O peak were studied in a set of individual experiments. It was
      concluded that most of this N2O originated during settling due to biological
      reactions. Complete oxidation of NH4+ (or most likely hydroxylamine) as a result
      of sufficient aeration time can be a minimization strategy for N2O emissions in
      partial nitrification systems.

PMID- 23561499
TI  - Chlorophenols breakdown by a sequential hydrodechlorination-oxidation treatment
      with a magnetic Pd-Fe/gamma-Al2O3 catalyst.
AB  - Degradation of chlorophenols by a sequential combination of hydrodechlorination
      (HDC) and catalytic wet peroxide oxidation (CWPO) using a new magnetic Pd
      Fe/gamma-Al2O3 catalyst has been studied. This catalyst is active in both
      hydrodechlorination of chlorophenols and decomposition of H2O2 for the oxidation
      of organic compounds. The sequential combination of HDC and CWPO allows
      overcoming some of the drawbacks of both treatments applied independently. The
      HDC step achieves the complete dechlorination of chlorophenols, so that the
      subsequent CWPO does not lead to the formation of highly toxic chlorinated by
      products and reduces significantly the organic load of the effluent. The results
      showed that the presence of iron in the Pd catalyst improved significantly its
      hydrodechlorination rate, achieving the complete dechlorination of chlorophenols
      in a short reaction time (~ 15 min), giving rise to phenol and cyclohexanone. The
      CWPO of synthetic mixtures of phenol and cyclohexanone showed that a high phenol
      concentration promotes the oxidation of all the organic species, but the presence
      of cyclohexanone seems to hinder the formation of aromatic radicals limiting the
      effectiveness of the CWPO step. Therefore, the effective combination of HDC and
      CWPO requires that the HDC step achieves the complete dechlorination of
      chlorophenols but no further hydrogenation is needed. The Pd-Fe/gamma-Al2O3
      catalyst showed a high activity in both HDC and subsequent CWPO of chlorophenols
      being easily separated and recovered from the reaction medium due to its
      ferromagnetic properties. In spite of a moderate loss of activity, the complete
      dechlorination of chlorophenol and a negligible ecotoxicity of the final
      effluents were maintained upon successive applications of HDC + CWPO in a four
      cycles test.

PMID- 23561500
TI  - Synthesis and characterization of novel antibacterial silver nanocomposite
      nanofiltration and forward osmosis membranes based on layer-by-layer assembly.
AB  - Using layer-by-layer (LbL) assembly method, we fabricated novel silver
      nanocomposite LbL-Ag nanofiltration (NF) and forward osmosis (FO) membranes. The
      incorporation of silver nanoparticles (AgNPs) in the membranes did not adversely
      affect the membrane separation performance in NF and FO processes at low AgNPs
      incorporation levels (0.22-1.19 wt.% as silver). The FO performance of the xLbL
      Ag membranes was better than or comparable to most NF-like FO membranes reported
      in the literature. In addition, the silver nanocomposite membranes exhibited
      excellent antibacterial properties against both Gram-positive Bacillus subtilis
      and Gram-negative Escherichia coli. Our results showed that the performances of
      the silver nanocomposite membranes are highly dependent on silver incorporation
      in the membranes, which could be controlled by using different membrane synthesis
      routines and doping of AgNPs. To the best knowledge of the authors, this is the
      first study on fabrication and characterization of novel antibacterial silver
      nanocomposite NF and FO membranes through LbL assembly approach.

PMID- 23561501
TI  - Toxicity of ionic liquid cations and anions towards activated sewage sludge
      organisms from different sources -- consequences for biodegradation testing and
      wastewater treatment plant operation.
AB  - Ionic liquids (ILs) have attracted great interest in academia and industry during
      the last decade. So far, several ILs have been used in technological processes,
      from small scale to industrial applications, which makes it more and more likely
      that they will be released into the environment. Researchers have been actively
      studying the environmental and toxicological behaviour of ILs, but their
      influence on the activated sludge communities of wastewater treatment plants have
      yet to be investigated. This study aims to fill this knowledge gap by
      systematically investigating the influence of ILs on activated sewage sludge
      communities. We tested the inhibition of activated sludge respiration (according
      to OECD guideline 209) by a selection of 19 different compounds covering the
      chemical space of ILs as comprehensively as possible. To elicit the differences
      in sensitivities/tolerances towards ILs we investigated activated sludge from
      different domestic and industrial sources. Generally speaking, the structure
      activity relationships of IL toxicity towards activated sludge are in good
      agreement with those found for other organisms and test systems. The inhibitory
      potential of tested ILs substituted with short alkyl chains (<= 4) and polar
      anions was low. On the other hand, the toxic effects of highly hydrophobic ionic
      cations and anions were greater - IC50 values were low, some < 50 MUM (<10 mg L(
      1)). We were able to demonstrate that the EC50 values from Vibrio fischeri can be
      used for a reliable assessment of the sludge inhibition potential of tested ILs.
      All the results are discussed in the context of their consequences for
      biodegradation processes and the performance of wastewater treatment plants.

PMID- 23561502
TI  - Microfauna communities as performance indicators for an A/O Shortcut Biological
      Nitrogen Removal moving-bed biofilm reactor.
AB  - The microfauna communities present in the mixed liquor and biofilm of an
      Anoxic/Oxic Shortcut Biofilm Nitrogen Removal moving-bed biofilm process were
      characterised in order to optimise process control through the use of
      bioindicators. The system operated at high ammonium concentrations, with an
      average of 588 +/- 220 mg N-NH4(+) L(-1) in the influent, 161 +/- 80 mg L(-1) in
      the anoxic reactor and 74 +/- 71.2 mg L(-1) in the aerobic reactor. Up to 20
      different taxa were identified, including ciliates (4), flagellates (11), amoebae
      (4) and nematodes (1). Compared to conventional wastewater treatment processes
      (WWTPs), this process can be defined as a flagellates-predominant system with a
      low diversity of ciliates. Flagellates were mainly dominant in the mixed liquor,
      demonstrating high tolerance to ammonium and the capacity for survival over a
      long time under anoxic conditions. The data obtained provide interesting values
      of maximum and minimum tolerance ranges to ammonium, nitrates and nitrites for
      the ciliate species Cyclidium glaucoma, Colpoda ecaudata, Vorticella microstoma
      complex and Epistylis cf. rotans. The last of these was the only ciliate species
      that presented a constant and abundant population, almost exclusively in the
      aerobic biofilm. Epistylis cf. rotans dynamics showed a high negative correlation
      with ammonium variations and a positive correlation with ammonium removal
      efficiency. Hence, the results indicate that Epistylis cf. rotans is a good
      bioindicator of the nitrification process in this system. The study of protozoan
      communities in unexplored WWTPs sheds light on species ecology and their role
      under conditions that have been little studied in WWTPs, and could offer new
      biological management tools.

PMID- 23561503
TI  - Enhanced sorption of naphthalene and p-nitrophenol by nano-SiO2 modified with a
      cationic surfactant.
AB  - In this study, we observed that modification of nano-oxides (e.g., nano-SiO2)
      with cationic surfactants (e.g., cetyl pyridinium chloride, CPC) could be a
      potential way to make nano-oxides be superior sorbents with a partition mechanism
      for the sorptive removal of organic contaminants from wastewater where the coated
      CPC was an effective organic phase for partitioning. The partitioning of nonpolar
      naphthalene into coated CPC was induced by hydrophobic effect alone and
      presenting linear isotherms, while that of polar p-nitrophenol was induced by not
      only the hydrophobic effect but also the hydrogen-bonding interaction and
      presenting isotherm nonlinearity. The sorption affinity for naphthalene and p
      nitrophenol partitioning into the coated CPC and the configuration of coated CPC
      remained unchanged although the amounts of coated CPC were increased. Linear
      relationships were established between the coated CPC amounts and the sorption
      capacities of naphthalene or p-nitrophenol, which could be used to predict the
      sorption of organic contaminants on surfactant-modified nano-oxides. In addition,
      these observed results would be also valuable for estimating the environmental
      behaviors and risks of nano-SiO2 and organic contaminants because nano-SiO2 would
      be inevitably coated with ubiquitous surfactants in the environment due to the
      discharging from the wide domestic and industry applications.

PMID- 23561504
TI  - Fatty acid content and composition of sediments from Siberian eutrophic water
      bodies: implications for biodiesel production.
AB  - We studied lipids and fatty acids (FA) in bottom sediments from four Siberian
      water bodies, Bugach, Lesnoi and Krasnoyarsk freshwater reservoirs and brackish
      Shira lake, that differed in physico-chemical and biological conditions. We
      considered the potential of the bottom sediments as a feedstock for biodiesel
      production and estimated properties of the obtained biodiesel as a fuel on the
      basis of FA composition. Contents of lipids and FA in the sediments moderately
      varied and were generally close to the reported data from lacustrine and
      estuarine systems. We confirmed that long-term eutrophication of a water body
      resulted in the lipid-rich bottom sediments that make them a feedstock for
      biodiesel production. Each of the studied water bodies had specific FA
      composition of sediments likely due to different organic matter sources and
      transformation processes. Despite these differences in FA profiles, calculated
      key parameters (cetane number, iodine number and heat of combustion) of biodiesel
      produced from all the studied sediments met the limits established by current
      biodiesel standards. Thus, the variation in the sediment FA composition due to
      environmental characteristics of a water body likely has no principal
      significance for fuel properties of the obtained biodiesel.

PMID- 23561505
TI  - Oxidation of Microcystis aeruginosa and Anabaena flos-aquae by ozone: impacts on
      cell integrity and chlorination by-product formation.
AB  - Pre-ozonation of cyanobacterial (CB) cells in raw water and inter-ozonation of
      settled water can cause CB cell damage. However, there is limited information
      about the level of lysis or changes in cell properties after ozonation, release
      of intracellular compounds and their contribution to the formation of
      disinfection by-products (DBPs). This study aims to: (1) assess the extent of the
      pre-ozonation effects on CB cell properties; (2) determine the CT (ozone
      concentration * detention time) values required for complete loss of cell
      viability; and (3) study the DBPs formation associated with the pre-ozonation of
      cyanobacterial cells in laboratorial suspensions. To these ends, both Microcystis
      aeruginosa and Anabaena flos-aquae suspensions were prepared at concentrations of
      250,000 cells mL(-1) and 1,500,000 cells mL(-1) and were subjected to ozone
      dosages of 0.5, 2.0 and 4.0 mg L(-1) at pH 6 and pH 8. A quick and complete loss
      of viability was achieved for both CB species after exposure (CT) to ozone of
      <0.2 mg min L(-1), although no significant decrease in total cell numbers was
      observed. Maximum dissolved organic carbon (DOC) releases of 0.96 mg L(-1) and
      1.63 mg L(-1) were measured after ozonation of 250,000 cells mL(-1) of M.
      aeruginosa and A. flos-aquae, respectively. DOC release was found to be pH and
      ozone dose dependent. Ozonation of CB cells increased formation of
      trihalomethanes (THM) and haloacetic acids (HAA), mainly for suspensions of A.
      flos-aquae at pH 8 (by 174% and 65% for THM and HAA respectively). Utilities
      considering using ozone for oxidising CB cells should weigh out the benefit of CB
      control with the potential increased formation of chlorinated DBPs.

PMID- 23561506
TI  - N-doped porous carbon with magnetic particles formed in situ for enhanced Cr(VI)
      removal.
AB  - A newly designed N-doped porous carbon with magnetic nanoparticles formed in situ
      (RHC-mag-CN) was fabricated through simple impregnation then polymerization and
      calcination. The doped nitrogen in RHC-mag-CN was in the form of graphite-type
      layers with the composition of CN. The resultant nanocomposite maintained a high
      surface area of 1136 m(2) g(-1) with 18.5 wt% magnetic nanoparticles (Fe3O4 and
      Fe) inside, which showed a saturation magnetization (Ms) of 22 emu/g. When used
      as an adsorbent, the RHC-mag-CN demonstrated a very quick adsorption property for
      the removal of Cr(VI), during which 92% of Cr(VI) could be removed within 10 min
      for dilute solutions at 2 g L(-1) adsorbent dose. The high adsorption capacity
      (16 mg g(-1)) is related to the synergetic effects of physical adsorption from
      the surface area and chemical adsorption from complexation reactions between
      Cr(VI) and Fe3O4. Importantly, the basic CNs in RHC-mag-CN increase its negative
      charge density and simultaneously increase the adsorption of metallic cations,
      such as Cr(3+) formed in the acid solution from the reduction of Cr(VI). The
      formation of magnetic nanoparticles inside not only supplies complexing sites for
      the adsorption of Cr(VI), but also shows perfect magnetic separation performance
      from aqueous solution.

PMID- 23561507
TI  - Transformation of silver nanoparticles in fresh, aged, and incinerated biosolids.
AB  - The purpose of this research was to assess the chemical transformation of silver
      nanoparticles (AgNPs) in aged, fresh, and incinerated biosolids in order to
      provide information for AgNP life cycle analyses. Silver nanoparticles were
      introduced to the influent of a pilot-scale wastewater (WW) treatment system
      consisting of a primary clarifier (PC), aeration basin, and secondary clarifier.
      The partitioning of the AgNPs between the aqueous and solid phases in the system
      was monitored. Less than 3% of the total AgNPs introduced into the PC were
      measured at the overflow of the PC. Biosolids were collected from the pilot-scale
      system for silver analyses, including Ag concentration and speciation.
      Additionally, biosolids were collected from a publically owned treatment works
      (POTW). The POTW biosolids were spiked with AgNPs, AgNO3, and Ag2S. One set of
      the spiked POTW biosolids was aged for one month, and another set was analyzed
      within 24 h via X-ray absorption spectroscopy (XAS) and scanning electron
      microscopy/energy dispersive X-ray spectroscopy (SEM-EDX) in order to determine
      Ag chemical speciation and elemental associations. Replicates of the aged and 24
      h samples were also incinerated at 850  degrees C for 4 h. The residual ash was
      analyzed by XAS and SEM-EDX. The results show that AgNPs are converted to Ag
      sulfur (as sulfide and sulfhydryl) species in fresh and aged biosolids, which is
      in agreement with other studies on AgNPs in biosolids. Results from linear
      combination fitting of the XAS data for incinerated biosolids show that a
      significant proportion of the spiked silver (30-50%) is converted to elemental Ag
      in the incineration process. In addition to elemental Ag, the results suggest the
      presence of additional Ag-S complexes such as Ag2SO4 (up to 25%), and silver
      associated with sulfhydryl groups (26-50%) in the incinerated biosolids.
      Incinerated biosolids spiked with AgNO3 and Ag2S exhibited similar
      transformations. These transformations of AgNPs should be accounted for in life
      cycle analyses of AgNPs and in management decisions regarding the disposal of
      incinerated biosolids.

PMID- 23561508
TI  - Increased blood-brain barrier vulnerability to systemic inflammation in an
      Alzheimer disease mouse model.
AB  - Behavioral and psychological problems are often observed in patients with
      dementia such as that associated with Alzheimer disease, and these noncognitive
      symptoms place an extremely heavy burden on the family and caregivers. Although
      it is well know that these symptoms often are triggered by infection of
      peripheral organs, the underlying mechanisms for these pathological conditions
      are still unclear. In this study, using an Alzheimer amyloid precursor protein
      (APP)-transgenic mouse, we analyzed behavioral changes and brain inflammatory
      response induced by peripheral administration of lipopolysaccharide. Application
      of a unique in vivo microdialysis system revealed that the increase in brain
      inflammatory cytokine (interleukin-6) level was significantly higher in APP-Tg
      than in wild-type mice after peripheral lipopolysaccharide injection, which was
      associated with more severe sickness behaviors. The blood-brain barrier became
      more permeable in APP-Tg mice during peripherally evoked inflammation, suggesting
      the increased vulnerability of the blood-brain barrier to inflammation in this
      animal model of Alzheimer's disease. These findings might provide insight into
      the pathogenesis of noncognitive symptoms in dementia and a basis to develop new
      therapeutic treatments for them.

PMID- 23561509
TI  - Different patterns of gray matter atrophy in early- and late-onset Alzheimer's
      disease.
AB  - We assessed patterns of gray matter atrophy according to-age-at-onset in a large
      sample of 215 Alzheimer's disease (AD) patients and 129 control subjects with
      voxel-based morphometry using 3-Tesla 3D T1-weighted magnetic resonance imaging.
      Local gray matter amounts were compared between late- and early-onset AD patients
      and older and younger control subjects, taking into account the effect of
      apolipoprotein E. Additionally, combined effects of age and diagnosis on volumes
      of hippocampus and precuneus were assessed. Compared with age-matched control
      subjects, late-onset AD patients exhibited atrophy of the hippocampus, right
      temporal lobe, and cerebellum, whereas early-onset AD patients showed gray matter
      atrophy in hippocampus, temporal lobes, precuneus, cingulate gyrus, and inferior
      frontal cortex. Direct comparisons between late- and early-onset AD patients
      revealed more pronounced atrophy of precuneus in early-onset AD patients and more
      severe atrophy in medial temporal lobe in late-onset AD patients. Age and
      diagnosis independently affected the hippocampus; moreover, the interaction
      between age and diagnosis showed that precuneus atrophy was most prominent in
      early-onset AD patients. Our results suggest that patterns of atrophy might vary
      in the spectrum of AD.

PMID- 23561510
TI  - The epidemiology of septic shock in French intensive care units: the prospective
      multicenter cohort EPISS study.
AB  - INTRODUCTION: To provide up-to-date information on the prognostic factors
      associated with 28-day mortality in a cohort of septic shock patients in
      intensive care units (ICUs). METHODS: Prospective, multicenter, observational
      cohort study in ICUs from 14 French general (non-academic) and university
      teaching hospitals. All consecutive patients with septic shock admitted between
      November 2009 and March 2011 were eligible for inclusion. We prospectively
      recorded data regarding patient characteristics, infection, severity of illness,
      life support therapy, and discharge. RESULTS: Among 10,941 patients admitted to
      participating ICUs between October 2009 and September 2011, 1,495 (13.7%)
      patients presented inclusion criteria for septic shock and were included.
      Invasive mechanical ventilation was needed in 83.9% (n=1248), inotropes in 27.7%
      (n=412), continuous renal replacement therapy in 32.5% (n=484), and hemodialysis
      in 19.6% (n=291). Mortality at 28 days was 42% (n=625). Variables associated with
      time to mortality, right-censored at day 28: age (for each additional 10 years)
      (hazard ratio (HR)=1.29; 95% confidence interval (CI): 1.20-1.38),
      immunosuppression (HR=1.63; 95%CI: 1.37-1.96), Knaus class C/D score versus class
      A/B score (HR=1.36; 95%CI:1.14-1.62) and Sepsis-related Organ Failure Assessment
      (SOFA) score (HR=1.24 for each additional point; 95%CI: 1.21-1.27). Patients with
      septic shock and renal/urinary tract infection had a significantly longer time to
      mortality (HR=0.56; 95%CI: 0.42-0.75). CONCLUSION: Our observational data of
      consecutive patients from real-life practice confirm that septic shock is common
      and carries high mortality in general ICU populations. Our results are in
      contrast with the clinical trial setting, and could be useful for healthcare
      planning and clinical study design.

PMID- 23561511
TI  - MscS inactivation: an exception rather than the rule. An extremophilic MscS
      reveals diversity within the family.

PMID- 23561512
TI  - Fluorescent dendritic nanoprobes: a new class of fluorescent probes for
      biological applications.

PMID- 23561513
TI  - Streaming potentials as novel driving force for capillary permeability.

PMID- 23561514
TI  - Pack it up, pack it in: unraveling H-NS mediated genome packaging.

PMID- 23561515
TI  - Lateral membrane diffusion corralled.

PMID- 23561516
TI  - Evanescent excitation and emission in fluorescence microscopy.
AB  - Evanescent light-light that does not propagate but instead decays in intensity
      over a subwavelength distance-appears in both excitation (as in total internal
      reflection) and emission (as in near-field imaging) forms in fluorescence
      microscopy. This review describes the physical connection between these two forms
      as a consequence of geometrical squeezing of wavefronts, and describes newly
      established or speculative applications and combinations of the two. In
      particular, each can be used in analogous ways to produce surface-selective
      images, to examine the thickness and refractive index of films (such as lipid
      multilayers or protein layers) on solid supports, and to measure the absolute
      distance of a fluorophore to a surface. In combination, the two forms can further
      increase selectivity and reduce background scattering in surface images. The
      polarization properties of each lead to more sensitive and accurate measures of
      fluorophore orientation and membrane micromorphology. The phase properties of the
      evanescent excitation lead to a method of creating a submicroscopic area of total
      internal reflection illumination or enhanced-resolution structured illumination.
      Analogously, the phase properties of evanescent emission lead to a method of
      producing a smaller point spread function, in a technique called virtual
      supercritical angle fluorescence.

PMID- 23561517
TI  - Fibers in the extracellular matrix enable long-range stress transmission between
      cells.
AB  - Cells can sense, signal, and organize via mechanical forces. The ability of cells
      to mechanically sense and respond to the presence of other cells over relatively
      long distances (e.g., ~100 MUm, or ~10 cell-diameters) across extracellular
      matrix (ECM) has been attributed to the strain-hardening behavior of the ECM. In
      this study, we explore an alternative hypothesis: the fibrous nature of the ECM
      makes long-range stress transmission possible and provides an important mechanism
      for long-range cell-cell mechanical signaling. To test this hypothesis, confocal
      reflectance microscopy was used to develop image-based finite-element models of
      stress transmission within fibroblast-seeded collagen gels. Models that account
      for the gel's fibrous nature were compared with homogenous linear-elastic and
      strain-hardening models to investigate the mechanisms of stress propagation.
      Experimentally, cells were observed to compact the collagen gel and align
      collagen fibers between neighboring cells within 24 h. Finite-element analysis
      revealed that stresses generated by a centripetally contracting cell boundary are
      concentrated in the relatively stiff ECM fibers and are propagated farther in a
      fibrous matrix as compared to homogeneous linear elastic or strain-hardening
      materials. These results support the hypothesis that ECM fibers, especially
      aligned ones, play an important role in long-range stress transmission.

PMID- 23561518
TI  - High-resolution 3D imaging and quantification of gold nanoparticles in a whole
      cell using scanning transmission ion microscopy.
AB  - Increasing interest in the use of nanoparticles (NPs) to elucidate the function
      of nanometer-sized assemblies of macromolecules and organelles within cells, and
      to develop biomedical applications such as drug delivery, labeling, diagnostic
      sensing, and heat treatment of cancer cells has prompted investigations into
      novel techniques that can image NPs within whole cells and tissue at high
      resolution. Using fast ions focused to nanodimensions, we show that gold NPs
      (AuNPs) inside whole cells can be imaged at high resolution, and the precise
      location of the particles and the number of particles can be quantified. High
      resolution density information of the cell can be generated using scanning
      transmission ion microscopy, enhanced contrast for AuNPs can be achieved using
      forward scattering transmission ion microscopy, and depth information can be
      generated from elastically backscattered ions (Rutherford backscattering
      spectrometry). These techniques and associated instrumentation are at an early
      stage of technical development, but we believe there are no physical constraints
      that will prevent whole-cell three-dimensional imaging at <10 nm resolution.

PMID- 23561519
TI  - Patch-clamp characterization of the MscS-like mechanosensitive channel from
      Silicibacter pomeroyi.
AB  - Based on sequence similarity, the sp7 gene product, MscSP, of the sulfur-compound
      decomposing Gram-negative marine bacterium Silicibacter pomeroyi belongs to the
      family of MscS-type mechanosensitive channels. To investigate MscSP channel
      properties, we measured its response to membrane tension using the patch-clamp
      technique on either a heterologous expression system using giant spheroplasts of
      MJF465 Escherichia coli strain (devoid of mechanosensitive channels MscL, MscS,
      and MscK), or on purified MscSP protein reconstituted in azolectin liposomes.
      These experiments showed typical pressure-dependent gating properties of a
      stretch-activated channel with a current/voltage plot indicating a rectifying
      behavior and weak preference for anions similar to the MscS channel of E. coli.
      However, the MscSP channel exhibited functional differences with respect to
      conductance and desensitization behavior, with the most striking difference
      between the two channels being the lack of inactivation in MscSP compared with
      MscS. This seems to result from the fact that although MscSP has a Gly in an
      equivalent position to MscS (G113), a position that is critical for inactivation,
      MscSP has a Glu residue instead of an Asn in a position that was recently shown
      to allosterically influence MscS inactivation, N117. To our knowledge, this study
      describes the first electrophysiological characterization of an MscS-like channel
      from a marine bacterium belonging to sulfur-degrading alpha-proteobacteria.

PMID- 23561520
TI  - The association of polar residues in the DAP12 homodimer: TOXCAT and molecular
      dynamics simulation studies.
AB  - Dimerization of the transmembrane (TM) adaptor protein DAP12 plays a key role in
      mediating activation signals through TM-TM association with cell-surface
      receptors. Herein, we apply the TOXCAT assay and molecular dynamics simulation to
      analyze dynamics and dimerization of the TM helix of DAP12 in the membrane
      bilayer. In the TOXCAT assay, we performed site-specific mutagenesis of potential
      dimerization motifs in the DAP12 TM domain. Instead of the common GxxxG
      dimerization motif, mutating either of the polar residues Asp-50 and Thr-54
      significantly decreased the TOXCAT signal for the dimerization of DAP12 TM
      domain. Furthermore, through the conformational difference between wild-type and
      mutant DAP12 TM homodimers, a combined coarse-grained and atomistic molecular
      dynamics simulation has identified both Asp-50 and Thr-54 at the dimerization
      interface. The experimental and computational results of the DAP12 TM dimer are
      in excellent agreement with the previously reported NMR structure obtained in
      detergent micelles. Such a combination of dynamics simulation and cell-based
      experiments can be applied to produce insights at the molecular level into the TM
      TM association of many other transmembrane proteins.

PMID- 23561521
TI  - Current fluctuation analysis of the PopB and PopD translocon components of the
      Pseudomonas aeruginosa type III secretion system.
AB  - Pseudomonas aeruginosa is a major agent of hospital-acquired infections, and a
      pathogen of immunocompromised, cystic fibrosis and burn patients. It uses a type
      III secretion system for the injection of toxins directly into host cells,
      through a translocon assembled in the host cell membrane. The hydrophobic
      translocator subunits of this system, PopB and PopD, have membrane permeabilizing
      activity based on previous dye leakage experiments, but little is known about the
      mechanism of assembly and the pore properties of this translocon. Using
      electrophysiology, we have observed that an equimolar mixture of PopB and PopD
      induces current fluctuations in planar lipid bilayers, with a unitary conductance
      of 57 pS in 1 M KCl and numerous larger conductance levels. The activity depends
      on voltage magnitude and polarity, and increases with protein concentration and
      the duration of the voltage step. PopB alone is sufficient for producing current
      fluctuations. PopD rarely displays any transitions, but accelerates PopB onset of
      activity. The effects of pH, ionic strength, and lipid composition have also been
      explored. Our data provide new, to our knowledge, insights into the behavior of
      PopB and PopD by highlighting similarities with secreted pore-forming peptides,
      and by suggesting that PopB/PopD may form channels via the toroidal pore model.
      We believe that the events we report here represent the initial steps of
      insertion and assembly of these translocators in the membrane.

PMID- 23561522
TI  - Phase diagram and tie-line determination for the ternary mixture
      DOPC/eSM/cholesterol.
AB  - We propose a novel, to our knowledge, method for the determination of tie lines
      in a phase diagram of ternary lipid mixtures. The method was applied to a system
      consisting of dioleoylphosphatidylcholine (DOPC), egg sphingomyelin (eSM), and
      cholesterol (Chol). The approach is based on electrofusion of single- or two
      component homogeneous giant vesicles in the fluid phase and analyses of the
      domain areas of the fused vesicle. The electrofusion approach enables us to
      create three-component vesicles with precisely controlled composition, in
      contrast to conventional methods for giant vesicle formation. The tie lines
      determined in the two-liquid-phase coexistence region are found to be not
      parallel, suggesting that the dominant mechanism of lipid phase separation in
      this region changes with the membrane composition. We provide a phase diagram of
      the DOPC/eSM/Chol mixture and predict the location of the critical point.
      Finally, we evaluate the Gibbs free energy of transfer of individual lipid
      components from one phase to the other.

PMID- 23561523
TI  - Lateral membrane diffusion modulated by a minimal actin cortex.
AB  - Diffusion of lipids and proteins within the cell membrane is essential for
      numerous membrane-dependent processes including signaling and molecular
      interactions. It is assumed that the membrane-associated cytoskeleton modulates
      lateral diffusion. Here, we use a minimal actin cortex to directly study proposed
      effects of an actin meshwork on the diffusion in a well-defined system. The
      lateral diffusion of a lipid and a protein probe at varying densities of membrane
      bound actin was characterized by fluorescence correlation spectroscopy (FCS). A
      clear correlation of actin density and reduction in mobility was observed for
      both the lipid and the protein probe. At high actin densities, the effect on the
      protein probe was ~3.5-fold stronger compared to the lipid. Moreover, addition of
      myosin filaments, which contract the actin mesh, allowed switching between fast
      and slow diffusion in the minimal system. Spot variation FCS was in accordance
      with a model of fast microscopic diffusion and slower macroscopic diffusion.
      Complementing Monte Carlo simulations support the analysis of the experimental
      FCS data. Our results suggest a stronger interaction of the actin mesh with the
      larger protein probe compared to the lipid. This might point toward a mechanism
      where cortical actin controls membrane diffusion in a strong size-dependent
      manner.

PMID- 23561524
TI  - Effects of pressure and electrical charge on macromolecular transport across
      bovine lens basement membrane.
AB  - Molecular transport through the basement membrane is important for a number of
      physiological functions, and dysregulation of basement membrane architecture can
      have serious pathological consequences. The structure-function relationships that
      govern molecular transport in basement membranes are not fully understood. The
      basement membrane from the lens capsule of the eye is a collagen IV-rich matrix
      that can easily be extracted and manipulated in vitro. As such, it provides a
      convenient model for studying the functional relationships that govern molecular
      transport in basement membranes. Here we investigate the effects of increased
      transmembrane pressure and solute electrical charge on the transport properties
      of the lens basement membrane (LBM) from the bovine eye. Pressure-permeability
      relationships in LBM transport were governed primarily by changes in diffusive
      and convective contributions to solute flux and not by pressure-dependent changes
      in intrinsic membrane properties. The solute electrical charge had a minimal but
      statistically significant effect on solute transport through the LBM that was
      opposite of the expected electrokinetic behavior. The observed transport
      characteristics of the LBM are discussed in the context of established membrane
      transport modeling and previous work on the effects of pressure and electrical
      charge in other basement membrane systems.

PMID- 23561525
TI  - The effect of sterols on amphotericin B self-aggregation in a lipid bilayer as
      revealed by free energy simulations.
AB  - Amphotericin B (AmB) is an effective but toxic antifungal drug, known to increase
      the permeability of the cell membrane, presumably by assembling into
      transmembrane pores in a sterol-dependent manner. The aggregation of AmB
      molecules in a phospholipid bilayer is, thus, crucial for the drug's activity. To
      provide an insight into the molecular nature of this process, here, we report an
      atomistic molecular dynamics simulation study of AmB head-to-head dimerization in
      a phospholipid bilayer, a possible early stage of aggregation. To compare the
      effect of sterols on the thermodynamics of aggregation and the architecture of
      the resulting AmB-AmB complexes, free energy profiles for the dimerization in
      ergosterol- or cholesterol-containing and sterol-free membranes are derived from
      the simulations. These profiles demonstrate that although AmB dimers are formed
      in all the systems studied, they are significantly less favorable in the bilayer
      with ergosterol than in the cholesterol-containing or sterol-free ones. We
      investigate the structural and energetic determinants of this difference and
      discuss its consequences for the AmB mechanism of action.

PMID- 23561527
TI  - Canonical azimuthal rotations and flanking residues constrain the orientation of
      transmembrane helices.
AB  - In biological membranes the alignment of embedded proteins provides crucial
      structural information. The transmembrane (TM) parts have well-defined secondary
      structures, in most cases alpha-helices and their orientation is given by a tilt
      angle and an azimuthal rotation angle around the main axis. The tilt angle is
      readily visualized and has been found to be functionally relevant. However, there
      exist no general concepts on the corresponding azimuthal rotation. Here, we show
      that TM helices prefer discrete rotation angles. They arise from a combination of
      intrinsic properties of the helix geometry plus the influence of the position and
      type of flanking residues at both ends of the hydrophobic core. The helical
      geometry gives rise to canonical azimuthal angles for which the side chains of
      residues from the two ends of the TM helix tend to have maximum or minimum
      immersion within the membrane. This affects the preferential position of residues
      that fall near hydrophobic/polar interfaces of the membrane, depending on their
      hydrophobicity and capacity to form specific anchoring interactions. On this
      basis, we can explain the orientation and dynamics of TM helices and make
      accurate predictions, which correspond well to the experimental values of several
      model peptides (including dimers), and TM segments of polytopic membrane
      proteins.

PMID- 23561526
TI  - Proline facilitates membrane insertion of the antimicrobial peptide maculatin 1.1
      via surface indentation and subsequent lipid disordering.
AB  - The role of proline in the disruption of membrane bilayer structure upon
      antimicrobial peptide (AMP) binding was studied. Specifically, (31)P and (2)H
      solid-state NMR and dual polarization interferometry (DPI) were used to analyze
      the membrane interactions of three AMPs: maculatin 1.1 and two analogs in which
      Pro-15 is replaced by Gly and Ala. For NMR, deuterated
      dimyristoylphosphatidylcholine (d54-DMPC) and d54
      DMPC/dimyristoylphosphatidylglycerol (DMPG) were used to mimic eukaryotic and
      prokaryotic membranes, respectively. In fluid-phase DMPC bilayer systems, the
      peptides interacted primarily with the bilayer surface, with the native peptide
      having the strongest interaction. In the mixed DMPC/DMPG bilayers, maculatin 1.1
      induced DMPG phase separation, whereas the analogs promoted the formation of
      isotropic and lipid-enriched phases with an enhanced effect relative to the
      neutral DMPC bilayers. In gel-phase DMPC vesicles, the native peptide disrupted
      the bilayer via a surface mechanism, and the effect of the analogs was similar to
      that observed in the fluid phase. Real-time changes in bilayer order were
      examined via DPI, with changes in bilayer birefringence analyzed as a function of
      the peptide mass bound to the bilayer. Although all three peptides decreased the
      bilayer order as a function of bound concentration, maculatin 1.1 caused the
      largest change in bilayer structure. The NMR data indicate that maculatin 1.1
      binds predominantly at the surface regions of the bilayer, and both NMR and DPI
      results indicate that this binding leads to a drop in bilayer order. Overall, the
      results demonstrate that the proline at residue 15 plays a central role in the
      membrane interaction of maculatin 1.1 by inducing a significant change in
      membrane order and affecting the ability of the bilayer to recover from
      structural changes induced by the binding and insertion of the peptide.

PMID- 23561528
TI  - Mechanical properties of doubly stabilized microtubule filaments.
AB  - Microtubules are cytoskeletal filaments responsible for cell morphology and
      intracellular organization. Their dynamical and mechanical properties are
      regulated through the nucleotide state of the tubulin dimers and the binding of
      drugs and/or microtubule-associated proteins. Interestingly, microtubule
      stabilizing factors have differential effects on microtubule mechanics, but
      whether stabilizers have cumulative effects on mechanics or whether one effect
      dominates another is not clear. This is especially important for the
      chemotherapeutic drug Taxol, an important anticancer agent and the only known
      stabilizer that reduces the rigidity of microtubules. First, we ask whether Taxol
      will combine additively with another stabilizer or whether one stabilizer will
      dominate another. We call microtubules in the presence of Taxol and another
      stabilizer, doubly stabilized. Second, since Taxol is often added to a number of
      cell types for therapeutic purposes, it is important from a biomedical
      perspective to understand how Taxol added to these systems affects the mechanical
      properties in treated cells. To address these questions, we use the method of
      freely fluctuating filaments with our recently developed analysis technique of
      bootstrapping to determine the distribution of persistence lengths of a large
      population of microtubules treated with different stabilizers, including Taxol,
      guanosine-5' [(alpha, beta)-methyleno] triphosphate, guanosine-5'-O-(3
      thiotriphosphate), tau, and MAP4. We find that combinations of these stabilizers
      have novel effects on the mechanical properties of microtubules.

PMID- 23561529
TI  - High-bandwidth AFM-based rheology reveals that cartilage is most sensitive to
      high loading rates at early stages of impairment.
AB  - Utilizing a newly developed atomic-force-microscopy-based wide-frequency rheology
      system, we measured the dynamic nanomechanical behavior of normal and
      glycosaminoglycan (GAG)-depleted cartilage, the latter representing matrix
      degradation that occurs at the earliest stages of osteoarthritis. We observed
      unique variations in the frequency-dependent stiffness and hydraulic permeability
      of cartilage in the 1 Hz-to-10 kHz range, a frequency range that is relevant to
      joint motions from normal ambulation to high-frequency impact loading.
      Measurement in this frequency range is well beyond the capabilities of typical
      commercial atomic force microscopes. We showed that the dynamic modulus of
      cartilage undergoes a dramatic alteration after GAG loss, even with the collagen
      network still intact: whereas the magnitude of the dynamic modulus decreased two-
      to threefold at higher frequencies, the peak frequency of the phase angle of the
      modulus (representing fluid-solid frictional dissipation) increased 15-fold from
      55 Hz in normal cartilage to 800 Hz after GAG depletion. These results, based on
      a fibril-reinforced poroelastic finite-element model, demonstrated that GAG loss
      caused a dramatic increase in cartilage hydraulic permeability (up to 25-fold),
      suggesting that early osteoarthritic cartilage is more vulnerable to higher
      loading rates than to the conventionally studied "loading magnitude". Thus, over
      the wide frequency range of joint motion during daily activities, hydraulic
      permeability appears the most sensitive marker of early tissue degradation.

PMID- 23561530
TI  - Solution structure of clostridial collagenase H and its calcium-dependent global
      conformation change.
AB  - Collagenase H (ColH) from Clostridium histolyticum is a multimodular protein
      composed of a collagenase module (activator and peptidase domains), two
      polycystic kidney disease-like domains, and a collagen-binding domain. The
      interdomain conformation and its changes are very important for understanding the
      functions of ColH. In this study, small angle x-ray scattering and limited
      proteolysis were employed to reveal the interdomain arrangement of ColH in
      solution. The ab initio beads model indicated that ColH adopted a tapered shape
      with a swollen head. Under calcium-chelated conditions (with EGTA), the overall
      structure was further elongated. The rigid body model indicated that the closed
      form of the collagenase module was preferred in solution. The limited proteolysis
      demonstrated that the protease sensitivity of ColH was significantly increased
      under the calcium-chelated conditions, and that the digestion mainly occurred in
      the domain linker regions. Fluorescence measurements with a fluorescent dye were
      performed with the limited proteolysis products after separation. The results
      indicated that the limited proteolysis products exhibited fluorescence similar to
      that of the full-length ColH. These findings suggested that the conformation of
      full-length ColH in solution is the elongated form, and this form is calcium
      dependently maintained at the domain linker regions.

PMID- 23561531
TI  - Comparative studies of disordered proteins with similar sequences: application to
      Abeta40 and Abeta42.
AB  - Quantitative comparisons of intrinsically disordered proteins (IDPs) with similar
      sequences, such as mutant forms of the same protein, may provide insights into
      IDP aggregation-a process that plays a role in several neurodegenerative
      disorders. Here we describe an approach for modeling IDPs with similar sequences
      that simplifies the comparison of the ensembles by utilizing a single library of
      structures. The relative population weights of the structures are estimated using
      a Bayesian formalism, which provides measures of uncertainty in the resulting
      ensembles. We applied this approach to the comparison of ensembles for Abeta40
      and Abeta42. Bayesian hypothesis testing finds that although both Abeta species
      sample beta-rich conformations in solution that may represent prefibrillar
      intermediates, the probability that Abeta42 samples these prefibrillar states is
      roughly an order of magnitude larger than the frequency in which Abeta40 samples
      such structures. Moreover, the structure of the soluble prefibrillar state in our
      ensembles is similar to the experimentally determined structure of Abeta that has
      been implicated as an intermediate in the aggregation pathway. Overall, our
      approach for comparative studies of IDPs with similar sequences provides a
      platform for future studies on the effect of mutations on the structure and
      function of disordered proteins.

PMID- 23561532
TI  - Molecular modeling and molecular dynamics simulations of recombinase Rad51.
AB  - The Rad51 ATPase plays central roles in DNA homologous recombination. Yeast Rad51
      dimer structure in the active form of the filament was constructed using homology
      modeling techniques, and all-atom molecular dynamics (MD) simulations were
      performed using the modeled structure. We found two crucial interaction networks
      involving ATP: one is among the gamma-phosphate of ATP, K(+) ions, H352, and
      D374; the other is among the adenine ring of ATP, R228, and P379. Multiple MD
      simulations were performed in which the number of bound K(+) ions was changed.
      The simulated structures suggested that K(+) ions are indispensable for the
      stabilization of the active dimer and resemble the arginine and lysine fingers of
      other P-loop containing ATPases and GTPases. MD simulations also showed that the
      adenine ring of ATP mediates interactions between adjacent protomers.
      Furthermore, in MD simulations starting from a structure just after ATP
      hydrolysis, the opening motion corresponding to dissociation from DNA was
      observed. These results support the hypothesis that ATP and K(+) ions function as
      glue between protomers.

PMID- 23561533
TI  - Dendrimer probes for enhanced photostability and localization in fluorescence
      imaging.
AB  - Recent advances in fluorescence microscopy have enabled high-resolution imaging
      and tracking of single proteins and biomolecules in cells. To achieve high
      spatial resolutions in the nanometer range, bright and photostable fluorescent
      probes are critically required. From this view, there is a strong need for
      development of advanced fluorescent probes with molecular-scale dimensions for
      fluorescence imaging. Polymer-based dendrimer nanoconjugates hold strong
      potential to serve as versatile fluorescent probes due to an intrinsic capacity
      for tailored spectral properties such as brightness and emission wavelength. In
      this work, we report a new, to our knowledge, class of molecular probes based on
      dye-conjugated dendrimers for fluorescence imaging and single-molecule
      fluorescence microscopy. We engineered fluorescent dendritic nanoprobes (FDNs) to
      contain multiple organic dyes and reactive groups for target-specific biomolecule
      labeling. The photophysical properties of dye-conjugated FDNs (Cy5-FDNs and Cy3
      FDNs) were characterized using single-molecule fluorescence microscopy, which
      revealed greatly enhanced photostability, increased probe brightness, and
      improved localization precision in high-resolution fluorescence imaging compared
      to single organic dyes. As proof-of-principle demonstration, Cy5-FDNs were used
      to assay single-molecule nucleic acid hybridization and for immunofluorescence
      imaging of microtubules in cytoskeletal networks. In addition, Cy5-FDNs were used
      as reporter probes in a single-molecule protein pull-down assay to characterize
      antibody binding and target protein capture. In all cases, the photophysical
      properties of FDNs resulted in enhanced fluorescence imaging via improved
      brightness and/or photostability.

PMID- 23561534
TI  - The shape of protein crowders is a major determinant of protein diffusion.
AB  - As a model for understanding how molecular crowding influences diffusion and
      transport of proteins in cellular environments, we combined experimental and
      theoretical approaches to study the diffusion of proteins in highly concentrated
      protein solutions. Bovine serum albumin and gamma-Globulin were chosen as
      molecular crowders and as tracers. These two proteins are representatives of the
      main types of plasma protein and have different shapes and sizes. Solutions
      consisting of one or both proteins were studied. The self-diffusion coefficients
      of the fluorescently labeled tracer proteins were measured by means of
      fluorescence correlation spectroscopy at a total protein concentration of up to
      400 g/L. gamma-Globulin is found to have a stronger influence as a crowder on the
      tracer self-diffusion coefficient than Bovine serum albumin. Brownian dynamics
      simulations show that the excluded volume and the shape of the crowding protein
      have a significantly stronger influence on translational and rotational diffusion
      coefficients, as well as transient oligomerization, than hydrodynamic or direct
      interactions. Anomalous subdiffusion, which is not observed at the experimental
      fluorescence correlation spectroscopy timescales (>100 MUs), appears only at very
      short timescales (<1 MUs) in the simulations due to steric effects of the
      proteins. We envision that the combined experimental and computational approach
      employed here can be developed to unravel the different biophysical contributions
      to protein motion and interaction in cellular environments by systematically
      varying protein properties such as molecular weight, size, shape, and
      electrostatic interactions.

PMID- 23561535
TI  - Allosteric control of syntaxin 1a by Munc18-1: characterization of the open and
      closed conformations of syntaxin.
AB  - Syntaxin 1a is a plasma membrane soluble N-ethylmaleimide-sensitive factor
      attachment receptor protein (SNARE) that contains an H3 domain (SNARE motif) and
      a regulatory Habc domain. These regions associate to produce a closed state,
      which is generally thought to suppress assembly of syntaxin into the SNARE
      complex. However, the molecular nature of the closed and open states of syntaxin
      is not well defined. Here, we use electron paramagnetic resonance spectroscopy to
      characterize conformational exchange in syntaxin. The data indicate that the H3
      segment is in equilibrium between ordered and disordered states that have
      significant populations. In solution, the central region of the H3 segment is
      positioned close to the Habc domain and the configuration of syntaxin 1a is
      dominated by a closed state. However, an open state is enhanced in full-length
      membrane reconstituted syntaxin. Munc18-1 binding alters the equilibrium along H3
      to favor the ordered, folded state. Munc18 also suppresses the minor open
      population and narrows the distance distributions between H3 and Habc. The
      allosteric control exhibited by Munc18 on the H3 segment and the suppression of
      the minor open component may both play a role in regulating membrane fusion by
      controlling the assembly of syntaxin into the SNARE complex.

PMID- 23561536
TI  - To build a virus on a nucleic acid substrate.
AB  - Many viruses package their genomes concomitant with assembly. Here, we show that
      this reaction can be described by three coefficients: association of capsid
      protein (CP) to nucleic acid (NA), KNA; CP-CP interaction, omega; and alpha,
      proportional to the work required to package NA. The value of alpha can vary as
      NA is packaged. A phase diagram of average lnalpha versus lnomega identifies
      conditions where assembly is likely to fail or succeed. NA morphology can favor
      (lnalpha > 0) or impede (lnalpha < 0) assembly. As lnomega becomes larger,
      capsids become more stable and assembly becomes more cooperative. Where (lnalpha
      + lnomega) < 0, the CP is unable to contain the NA, so that assembly results in
      aberrant particles. This phase diagram is consistent with quantitative studies of
      cowpea chlorotic mottle virus, hepatitis B virus, and simian virus 40 assembling
      on ssRNA and dsDNA substrates. Thus, the formalism we develop is suitable for
      describing and predicting behavior of experimental studies of CP assembly on NA.

PMID- 23561537
TI  - A tunable, modular approach to fluorescent protease-activated reporters.
AB  - Proteases are one of the most important and historically utilized classes of drug
      targets. To effectively interrogate this class of proteins, which encodes nearly
      2% of the human proteome, it is necessary to develop effective and cost-efficient
      methods that report on their activity both in vitro and in vivo. We have
      developed a robust reporter of caspase proteolytic activity, called caspase
      activatable green fluorescent protein (CA-GFP). The caspases play central roles
      in homeostatic regulation, as they execute programmed cell death, and in drug
      design, as caspases are involved in diseases ranging from cancer to
      neurodegeneration. CA-GFP is a genetically encoded dark-to-bright fluorescent
      reporter of caspase activity in in vitro, cell-based, and animal systems. Based
      on the CA-GFP platform, we developed reporters that can discriminate the
      activities of caspase-6 and -7, two highly related proteases. A second series of
      reporters, activated by human rhinovirus 3C protease, demonstrated that we could
      alter the specificity of the reporter by reengineering the protease recognition
      sequence. Finally, we took advantage of the spectrum of known fluorescent
      proteins to generate green, yellow, cyan, and red reporters, paving the way for
      multiplex protease monitoring.

PMID- 23561538
TI  - A model of H-NS mediated compaction of bacterial DNA.
AB  - The histone-like nucleoid structuring protein (H-NS) is a nucleoid-associated
      protein, which is involved in both gene regulation and DNA compaction. H-NS can
      bind to DNA in two different ways: in trans, by binding to two separate DNA
      duplexes, or in cis, by binding to different sites on the same duplex. Based on
      scanning force microscopy imaging and optical trap-driven unzipping assays, it
      has recently been suggested that DNA compaction may result from the antagonistic
      effects of H-NS binding to DNA in trans and cis configurations. To get more
      insight into the compaction mechanism, we constructed a coarse-grained model
      description of the compaction of bacterial DNA by H-NS. These simulations
      highlight the fact that DNA compaction indeed results from the subtle equilibrium
      between several competing factors, which include the deformation dynamics of the
      plasmid and the several binding modes of protein dimers to DNA, i.e., dangling
      configurations, cis- and trans-binding. In particular, the degree of compaction
      is extremely sensitive to the difference in binding energies of the cis and trans
      configurations. Our simulations also point out that the conformations of the DNA
      protein complexes are significantly different in bulk and in planar conditions,
      suggesting that conformations observed on mica surfaces may differ significantly
      from those that prevail in living cells.

PMID- 23561541
TI  - Interindividual concurrence in interpretation of findings of hysteroscopic
      videos.

PMID- 23561540
TI  - Gbetagamma-mediated activation of protein kinase D exhibits subunit specificity
      and requires Gbetagamma-responsive phospholipase Cbeta isoforms.
AB  - BACKGROUND: Protein kinase D (PKD) constitutes a novel family of serine/threonine
      protein kinases implicated in fundamental biological activities including cell
      proliferation, survival, migration, and immune responses. Activation of PKD in
      these cellular activities has been linked to many extracellular signals acting
      through antigen receptor engagement, receptor tyrosine kinases, as well as G
      protein-coupled receptors. In the latter case, it is generally believed that the
      Galpha subunits of the Gq family are highly effective in mediating PKD
      activation, whereas little is known with regard to the ability of Gbetagamma
      dimers and other Galpha subunits to stimulate PKD. It has been suggested that the
      interaction between Gbetagamma and the PH domain of PKD, or the Gbetagamma
      induced PLCbeta/PKC activity is critical for the induction of PKD activation.
      However, the relative contribution of these two apparently independent events to
      Gbetagamma-mediated PKD activation has yet to be addressed. RESULTS: In this
      report, we demonstrate that among various members in the four G protein families,
      only the Galpha subunits of the Gq family effectively activate all the three PKD
      isoforms (PKD1/2/3), while Galpha subunits of other G protein families (Gs, Gi,
      and G12) are ineffective. Though the Galpha subunits of Gi family are unable to
      stimulate PKD, receptors linked to Gi proteins are capable of triggering PKD
      activation in cell lines endogenously expressing (HeLa cells and Jurkat T-cells)
      or exogenously transfected with (HEK293 cells) Gbetagamma-sensitive PLCbeta2/3
      isoforms. This indicates that the Gi-mediated PKD activation is dependent on the
      released Gbetagamma dimers upon stimulation. Further investigation on individual
      Gbetagamma combinations (i.e. Gbeta1 with Ggamma1-13) revealed that, even if they
      can stimulate the PLCbeta activity in a comparable manner, only those Gbeta1gamma
      dimers with gamma2, gamma3, gamma4, gamma5, gamma7, and gamma10 can serve as
      effective activators of PKD. We also demonstrated that Gi-mediated PKD activation
      is essential for the SDF-1alpha-induced chemotaxis on Jurkat T-cells.
      CONCLUSIONS: Our current report illustrates that Gbetagamma dimers from the Gi
      proteins may activate PKD in a PLCbeta2/3-dependent manner, and the specific
      identities of Ggamma components within Gbetagamma dimers may determine this
      stimulatory action.

PMID- 23561539
TI  - Novel role for vinculin in ventricular myocyte mechanics and dysfunction.
AB  - Vinculin (Vcl) plays a key structural role in ventricular myocytes that, when
      disrupted, can lead to contractile dysfunction and dilated cardiomyopathy. To
      investigate the role of Vcl in myocyte and myocardial function, cardiomyocyte
      specific Vcl knockout mice (cVclKO) and littermate control wild-type mice were
      studied with transmission electron microscopy (TEM) and in vivo magnetic
      resonance imaging (MRI) tagging before the onset of global ventricular
      dysfunction. MRI revealed significantly decreased systolic strains transverse to
      the myofiber axis in vivo, but no changes along the muscle fibers or in fiber
      tension in papillary muscles from heterozygous global Vcl null mice. Myofilament
      lattice spacing from TEM was significantly greater in cVclKO versus wild-type
      hearts fixed in the unloaded state. AFM in Vcl heterozygous null mouse myocytes
      showed a significant decrease in membrane cortical stiffness. A multiscale
      computational model of ventricular mechanics incorporating cross-bridge geometry
      and lattice mechanics showed that increased transverse systolic stiffness due to
      increased lattice spacing may explain the systolic wall strains associated with
      Vcl deficiency, before the onset of ventricular dysfunction. Loss of cardiac
      myocyte Vcl may decrease systolic transverse strains in vivo by decreasing
      membrane cortical tension, which decreases transverse compression of the lattice
      thereby increasing interfilament spacing and stress transverse to the myofibers.

PMID- 23561542
TI  - Changes in DNA fragmentation during sperm preparation for intracytoplasmic sperm
      injection over time.
AB  - OBJECTIVE: To compare the DNA fragmentation of semen samples established by
      terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)
      after incubation in polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) for
      different time periods. DESIGN: Comparative prospective study. SETTING: Center
      for reproductive medicine. PATIENT(S): Twenty-seven semen samples from infertile
      patients. INTERVENTION(S): None. METHODS: Semen analysis and DNA fragmentation
      assays (TUNEL) were performed. Two groups were established: A) normal TUNEL
      (<20%); and B) Abnormal TUNEL (>= 20%). TUNEL was performed in neat (T0),
      postgradient (TG), 1-hour postgradient (TG1), and 2-hour postgradient (TG2)
      samples and in TG2 samples after 0.5, 1.0, and 1.5 hours of incubation in PVP or
      HA. RESULT(S): TUNEL levels were significantly reduced after gradient separation
      compared with neat values. In group A, TUNEL levels were significantly higher in
      the TG2 + 1.5 hours in PVP and HA samples but did not reach abnormal levels. In
      group B, TUNEL levels were significantly higher in the TG2 + 1 hour in PVP and HA
      samples. CONCLUSION(S): Sperm DNA fragmentation significantly decreased after
      centrifugation gradient, regardless of the initial levels of the sample. Samples
      with TUNEL >= 20% were more susceptible to a significant increase in DNA
      fragmentation over time, with similar increases being observed over time for
      samples that were incubated in HA or PVP. These data may be relevant for sperm
      preparation for intracytoplasmic sperm injection.

PMID- 23561545
TI  - Acute dystonic reaction with rivastigmine.
AB  - Dystonic reactions are adverse extrapyramidal side effects and are common to
      antipsychotics, antiemetics, and a variety of other drugs. Rivastigmine, an
      anticholinesterase of carbamate variety, is well tolerated. A case of acute
      dystonic reaction with rivastigmine patch is being reported.

PMID- 23561547
TI  - A novel conserved mutation in SGCE gene in 3 unrelated patients with classical
      phenotype myoclonus-dystonia syndrome.
AB  - OBJECTIVE AND IMPORTANCE: Myoclonus-dystonia syndrome (MDS, DYT11) is an
      inherited disorder characterized by clinical and genetic heterogeneity. MDS is
      inherited in autosomal dominant pattern and caused by heterozygous mutations in
      the gene encoding epsilon-sarcoglycan (SGCE) on chromosome 7q21. SGCE gene
      mutations are present in about 30-50% patients classified as definite-MDS.
      Earlier onset of motor symptoms is indicated in MDS patients who are SGCE
      mutations carriers. We present clinical phenotype of three unrelated MDS patients
      bearing novel, not described yet, mutation in SGCE gene. CLINICAL PRESENTATION:
      Presence of a substantial mutation in exon 3, changing aspartic acid to
      asparagine in codon 96 (D96N) of SGCE protein has been revealed. Three unrelated
      individuals, bearing the same mutation have diversity of symptoms, with some
      common features. Age of onset of our patients differs: 2, 14 to 38 years of age.
      Intervention/technique: Detection of mutations in SGCE gene was performed via
      direct sequencing of SGCE gene. CONCLUSIONS: Our results confirm the role of the
      SGCE gene in the pathogenesis of MDS and call into question the impact of SGCE
      mutations on the age of onset. The existing list of known mutations and diversity
      of symptoms in patients bearing the same mutation indicates that there is a lack
      of genotype-phenotype correlation. Heterogeneity of disease indicates necessity
      for further research in order to find the molecular fingerprint which may be a
      landmark in diagnostic studies of MDS.

PMID- 23561548
TI  - Numerical simulation of hemodynamics in intracranial saccular aneurysm treated
      with a novel stent.
AB  - Different from the traditional stents, a novel stent with triangular wire cross
      section is proposed, and numerical simulation is performed to compare the
      hemodynamic effect of the novel stent with that of traditional ones. Three kinds
      of stents with circular, rectangular, and triangular wire cross-sections were
      designed to treat saccular aneurysm, which were named the C-stent model, the R
      stent model, and the T-stent model, respectively. An unstented aneurysm model
      (named the Unstented model), as a control, was also designed. Fluid-structure
      interaction in these four models was simulated. The results demonstrate that the
      resistance of the novel T-stent model is lower than that of the R-stent model,
      but higher than that of the C-stent model. Compared with the C-stent model, the T
      stent model exhibits greater velocity decrease and longer turnover time.
      Meanwhile, the pressure increase of the T-stent model is lower than the R-stent
      model, and the magnitude and the fluctuation of wall shear stress is optimized in
      the T-stent model. The novel stent with a bare triangular wire cross-section has
      some comparative advantages. These results may provide some theoretical guidance
      for the structural design of an endovascular stent for the interventional
      treatment of aneurysm. 

PMID- 23561551
TI  - Dependence of image quality on acquisition time for the PET/CT Biograph mCT.
AB  - The impact of acquisition time on reconstructed PET image quality is analyzed for
      different acquisition times (1, 2, 3 and 4min). Image quality was tested
      according to the National Electrical Manufacturers Association (NEMA) NU 2-2007,
      the evaluation for the signal to noise ratio (SNR) and the reconstructed activity
      ratio (RAR) for three algorithms, i.e. OSEM, TrueX and TOF applying different
      effective iteration numbers. The present work shows that the image quality of 3
      and 4min acquisition time for spherical lesions of 10mm diameter are not
      significantly different between TrueX, TOF and OSEM. The 2min acquisition time
      should be used carefully for the TrueX and OSEM algorithms in small lesions,
      because the levels of background noise are high compared to 3 or 4min
      measurements. Also, the reconstructed activity ratio is underestimated to be
      approximately half of the expected value. For large lesions the three algorithms
      perform similarly for all acquisition durations, however, OSEM has the advantage
      of a more accurately reconstructed activity ratio compared to TrueX and TOF,
      which are more strongly influenced by noise. 

PMID- 23561552
TI  - Cloning and expression of candidate allergens from Culicoides obsoletus for
      diagnosis of insect bite hypersensitivity in horses.
AB  - Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity
      reaction induced by allergens from biting midges of the Culicoides spp. The aim
      of the present study was to identify, clone and express recombinant allergens
      from C. obsoletus, the main species found feeding on horses in the Netherlands,
      by sequence homology searches on the C. obsoletus specific RNA database, with
      previously described allergens from C. nubeculosus and C. sonorensis. BLAST
      searches with these described allergens resulted in similarity hits with 7 genes
      coding for C. obsoletus allergens. These allergens were expressed as
      hexahistidine tagged recombinant proteins in E. coli. Allergens were termed Cul o
      1-Cul o 7. A maltase (Cul o 1) plus Cul s 1 (maltase of C. sonorensis) were
      additionally expressed in insect cells using the baculovirus expression system to
      compare homologous allergens from different species produced with different
      expression systems in diagnostic in vitro and in vivo tests. We demonstrate that
      IBH affected horses in the Netherlands show higher IgE levels to Cul o 1 than to
      Cul s 1, as determined by an IgE ELISA. Furthermore, we show that Cul o 1
      produced in E. coli is at least as suitable for in vitro diagnosis of IBH
      affected horses as Cul o 1 produced in the baculovirus/insect cell expression
      system. The resulting proteins were evaluated for their ability to discriminate
      IBH affected and healthy horses by ELISA and intradermal testing. The frequency
      of positive test results by ELISA within IBH affected horses ranged from 38% to
      67% for the different allergens. When results of IgE-binding to Cul o 1-Cul o 7
      were combined the test had a sensitivity of 92% and specificity of 85%. The
      capability of the allergens to induce Type I hypersensitivity reaction in IBH
      affected horses was demonstrated by an intradermal test. The results show that E.
      coli expressed recombinant allergens from C. obsoletus are valuable tools to
      determine the allergen specific sensitisation profile (component resolved
      diagnosis) in horses with IBH in countries were C. obsoletus is the most abundant
      species and may facilitate in the development of future immunotherapy.

PMID- 23561550
TI  - miR-411 is up-regulated in FSHD myoblasts and suppresses myogenic factors.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal
      dominant muscle disorder, which is linked to the contraction of the D4Z4 array at
      chromosome 4q35. Recent studies suggest that this shortening of the D4Z4 array
      leads to aberrant expression of double homeobox protein 4 (DUX4) and causes FSHD.
      In addition, misregulation of microRNAs (miRNAs) has been reported in muscular
      dystrophies including FSHD. In this study, we identified a miRNA that is
      differentially expressed in FSHD myoblasts and investigated its function.
      METHODS: To identify misregulated miRNAs and their potential targets in FSHD
      myoblasts, we performed expression profiling of both miRNA and mRNA using TaqMan
      Human MicroRNA Arrays and Affymetrix Human Genome U133A plus 2.0 microarrays,
      respectively. In addition, we over-expressed miR-411 in C2C12 cells to determine
      the effect of miR-411 on myogenic markers. RESULTS: Using miRNA and mRNA
      expression profiling, we identified 8 miRNAs and 1,502 transcripts that were
      differentially expressed in FSHD myoblasts during cell proliferation. One of the
      8 differentially expressed miRNAs, miR-411, was validated by quantitative RT-PCR
      in both primary (2.1 fold, p<0.01) and immortalized (2.7 fold, p<0.01) myoblasts.
      In situ hybridization showed cytoplasmic localization of miR-411 in FSHD
      myoblasts. By analyzing both miRNA and mRNA data using Partek Genomics Suite, we
      identified 4 mRNAs potentially regulated by miR-411 including YY1 associated
      factor 2 (YAF2). The down-regulation of YAF2 in immortalized myoblasts was
      validated by immunoblotting (-3.7 fold, p<0.01). C2C12 cells were transfected
      with miR-411 to determine whether miR-411 affects YAF2 expression in myoblasts.
      The results showed that over-expression of miR-411 reduced YAF2 mRNA expression.
      In addition, expression of myogenic markers including Myod, myogenin, and myosin
      heavy chain 1 (Myh1) were suppressed by miR-411. CONCLUSIONS: The study
      demonstrated that miR-411 was differentially expressed in FSHD myoblasts and may
      play a role in regulating myogenesis.

PMID- 23561553
TI  - Clinical and radiographic evaluation of the adult spinal deformity patient.
AB  - Among the prevalent forms of adult spinal deformity are residual adolescent
      idiopathic and degenerative scoliosis, kyphotic deformity, and spondylolisthesis.
      Clinical evaluation should include a thorough history, discussion of concerns,
      and a review of comorbidities. Physical examination should include assessment of
      the deformity and a neurologic examination. Imaging studies should include full
      length standing posteroanterior and lateral spine radiographs, and measurement of
      pelvic parameters. Advanced imaging studies are frequently indicated to assess
      for neurologic compromise and for surgical planning. This article focuses on
      clinical and radiographic evaluation of spinal deformity in the adult population,
      particularly scoliosis and kyphotic deformities.

PMID- 23561554
TI  - Sagittal spinal pelvic alignment.
AB  - The goal of any ambulatory patient is to maintain a horizontal gaze with the
      least amount of energy expenditure. With progressive deformity, and in particular
      sagittal malalignment, significant compensatory mechanisms must be used to
      achieve this goal. Each pelvis dictates the amount of lumbar lordosis required
      through its morphometric parameter pelvic incidence. The pelvis may compensate
      for decreasing lumbar lordosis (eg, age, flat back deformity) by retroverting and
      increasing pelvic tilt and decreasing the sacral slope. Underappreciation for
      these spinopelvic compensatory mechanisms leads to surgical under-correction,
      iatrogenic flat back and poor clinical outcomes.

PMID- 23561555
TI  - Use of Surgimap Spine in sagittal plane analysis, osteotomy planning, and
      correction calculation.
AB  - Over the past 3 decades the sagittal plane has received increasing attention from
      the scientific community and spine surgeons alike. There remains a lack of clear
      and concise methods for incorporating surgical techniques and radiographic
      parameters to achieve the best possible outcome on a patient-specific level. This
      article proposes a new method for a treatment approach to sagittal malalignment
      by incorporating new digital tools for surgical planning. This technique offers a
      consistent approach to adult spinal deformity with sagittal-plane components, and
      can permit optimization in consistently achieving proper postoperative
      spinopelvic alignment.

PMID- 23561556
TI  - Adolescent scoliosis classification and treatment.
AB  - Adolescent idiopathic scoliosis (AIS) affects up to 3% of the population. It can
      be stratified by curve type according to the Lenke classification. This
      classification system incorporates curve magnitude, flexibility, the lumbar
      modifier, and the sagittal plane. The Lenke classification serves as a guide for
      selection of levels for surgical treatment of AIS. Surgical treatment of AIS
      includes anterior and posterior approaches; most AIS is treated through a
      posterior approach. Surgical goals include maximizing correction in the coronal,
      sagittal, and axial planes.

PMID- 23561557
TI  - Classifications for adult spinal deformity and use of the Scoliosis Research
      Society-Schwab Adult Spinal Deformity Classification.
AB  - Adult spinal deformity (ASD) is a complex disease state that pathologically
      alters standing upright posture and is associated with substantial pain and
      disability. This article provides an overview of classification systems for
      spinal deformity, clarifies the need to differentiate between pediatric and adult
      classifications, and provides an explanation on the use of the Scoliosis Research
      Society-Schwab Adult Spinal Deformity Classification (SRS-Schwab ASD
      Classification). This information allows surgeons, researchers, and health care
      providers to (1) identify sources of pain and disability in patients with ASD and
      (2) accurately use the SRSeSchwab ASD Classification to evaluate patients with
      ASD.

PMID- 23561558
TI  - Coronal realignment and reduction techniques and complication avoidance.
AB  - Scoliosis is a broad term encompassing multiple pathologies with different
      etiologies. Patients may range from the infant with congenital deformity, to the
      adolescent with idiopathic scoliosis, to the elderly patient with severe
      degenerative scoliosis. Treatment must be tailored to individual circumstances
      and the pathoanatomy of each deformity. Various coronal reduction techniques have
      been described and will be discussed within this article. While scoliosis is
      generally considered a deformity in the coronal plane, often deformity is present
      in the sagittal and axial planes also. Treatment of these deformities can require
      osteotomies or vertebral column resections, techniques further discussed in
      accompanying articles.

PMID- 23561559
TI  - Spinal osteotomies for rigid deformities.
AB  - Various osteotomies are useful in making a rigid deformity flexible enough for
      realignment in coronal and sagittal plane. This article defines the osteotomies
      and their usefulness in treatment of specific rigid deformities. The pedicle
      subtraction osteotomy and vertebral column resection used in treating rigid
      deformities are described in detail.

PMID- 23561560
TI  - Proximal junctional kyphosis and proximal junctional failure.
AB  - Proximal junctional failure (PJF) should be distinguished from proximal
      junctional kyphosis, which is a recurrent deformity with limited clinical impact.
      PJF includes mechanical failure, and is a significant complication following
      adult spinal deformity surgery with potential for neurologic injury and increased
      need for surgical revision. Risk factors for PJF include age, severity of
      sagittal plane deformity, and extent of operative sagittal plane realignment.
      Techniques for avoiding PJF will likely require refinements in both perioperative
      and surgical strategies.

PMID- 23561561
TI  - Treatment algorithms and protocol practice in high-risk spine surgery.
AB  - The practice of appropriate evidence-based medicine should be a goal for all
      physicians. By using protocols in areas where strong evidence-based medicine
      exists, physicians have reliably shown they can improve patient outcomes while
      reducing complications, cost, and hospital stay. Evidence-based protocols in
      complex spinal care are rare. At Northwestern University the authors have
      developed a multidisciplinary protocol for the preoperative, intraoperative, and
      postoperative workup and care of complex spine patients. The rationale and use of
      the High-Risk Spine Protocol is discussed.

PMID- 23561562
TI  - The role of minimally invasive techniques in the treatment of adult spinal
      deformity.
AB  - Many surgeons use minimally invasive surgery (MIS) approaches for treatment of
      patients with adult degenerative spinal deformity. The feasibility and efficacy
      of these techniques in the treatment of certain subtypes of degenerative
      deformities have been reported. In this article, several MIS techniques are
      discussed and an established 6-level treatment algorithm (MiSLAT) is presented,
      to help guide spinal surgeons in the use of MIS techniques for the treatment of
      patients with degenerative deformity. MIS treatment of MiSLAT level I to IV
      deformities is recommended, whereas level V and VI deformities require more
      traditional open approaches for adequate deformity correction.

PMID- 23561563
TI  - Assessment and treatment of cervical deformity.
AB  - Cervical deformity is disruption of normal cervical alignment. This article
      focuses on the varying etiology of cervical deformity, normative data, and
      evaluation and examination of deformity, and presents various treatment options
      for the proper management of these debilitating conditions. Surgical treatment
      may be indicated in patients with severe mechanical neck pain, neurologic
      compromise, and progressive deformity causing significant disability, such as
      dysphagia or loss of horizontal gaze.

PMID- 23561564
TI  - Management of high-grade spondylolisthesis.
AB  - Management of high-grade spondylolisthesis (HGS) remains challenging and is
      associated with significant controversies. The best surgical procedure remains
      debatable. Although the need for instrumentation is generally agreed upon,
      significant controversies still surround the role of reduction and anterior
      column support in the surgical management of HGS. Complications with operative
      management of HGS can be significant and often dictate the selection of surgical
      approach. This review highlights the pathophysiology, classification, clinical
      presentation, and management controversies of HGS, in light of recent advances in
      our understanding of the importance of sagittal spinopelvic alignment and
      technologic advancements.

PMID- 23561565
TI  - Health economic analysis of adult deformity surgery.
AB  - Given the substantial growth in frequency and expense of spine deformity surgery,
      and the general economic landscape of the health care system, health economics
      research has an important role in the literature on adult spinal deformity (ASD).
      The purpose of this article is to provide an update on the current state of
      health economics studies in the ASD literature and to introduce areas in which
      health economics might play some additional role in future research on ASD.

PMID- 23561566
TI  - Spinal deformity surgery.

PMID- 23561567
TI  - [Need to intensify the relationship with medicine from primary care to improve
      the control and treatment of patients infected by the virus of hepatitis B].

PMID- 23561568
TI  - Direct competitive immunosorbent assay for detection of MEHP in human urine.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer for
      flexible polyvinyl chloride (PVC), which is also known as one of the
      environmental endocrine disruptors with the reproductive, developmental and
      embryonic toxicity after entering human body. Mono-2-ethylhexyl phthalate (MEHP)
      is one of the most complicate metabolites from DEHP in vivo and responsible for
      many toxic effects of DEHP. In order to evaluate human exposure to DEHP, a direct
      competitive enzyme-linked immunosorbent (dcELISA) based on monoclonal antibody
      (mAb) was developed to detect MEHP. A hybridoma cell line 4B9 secreting mAb
      against MEHP was prepared, and the horseradish peroxidase (HRP) labeled antigen
      as a probe in the dcELISA was made. After optimization of ELISA reaction
      conditions, the standard curve with a linear range from 0.56 to 1000 ng mL(-1)
      and a detection limit of 0.39 ng mL(-1) was established. The cross-reactivities
      of anti-MEHP mAb to other ten phthalate esters were less than 5% except for mono
      methylphthalate (MME). The average recoveries of MEHP from distilled water and
      negative human urine were both between 87.4% and 94.72% with coefficient of
      variation (CV) less than 5%. Here, the ELISA method on detecting MEHP was
      successfully established and applied to real urine sample analyses and the
      results were confirmed by HPLC. Furthermore, it was indicated that the
      immunoassay was reliable and suitable for monitoring MEHP.

PMID- 23561569
TI  - Mineralization of sulfanilamide by electro-Fenton and solar photoelectro-Fenton
      in a pre-pilot plant with a Pt/air-diffusion cell.
AB  - The mineralization of sulfanilamide solutions at pH 3.0 was comparatively studied
      by electro-Fenton (EF) and solar photoelectro-Fenton (SPEF) using a 2.5 L pre
      pilot plant containing a Pt/air-diffusion cell coupled with a solar photoreactor.
      Organics were primordially oxidized by hydroxyl radical (OH) formed from Fenton's
      reaction between H2O2 generated at the cathode and added Fe(2+) and/or under the
      action of sunlight. A mineralization up to 94% was achieved using SPEF, whereas
      EF yielded much poorer degradation. The effect of current density and Fe(2+) and
      drug concentrations on the degradation rate, mineralization current efficiency
      and energy cost per unit DOC mass of EF and/or SPEF was examined. The
      sulfanilamide decay always followed a pseudo first-order kinetics, being more
      rapid in SPEF due to the additional generation of OH induced by sunlight on
      Fe(III) species. Catechol, resorcinol, hydroquinone and p-benzoquinone were
      identified as aromatic intermediates. The final solutions treated by EF contained
      Fe(III) complexes of maleic, fumaric, oxamic and mainly oxalic acids, which are
      hardly destroyed by OH. The quick photolysis of Fe(III)-oxalate complexes by
      sunlight explains the higher oxidation ability of SPEF. The N content of
      sulfanilamide was mainly mineralized as NH4+ ion and in much lesser extent as NO3
      ion, whereas most of its initial S was converted into SO42- ion.

PMID- 23561570
TI  - In situ air-water and particle-water partitioning of perfluorocarboxylic acids,
      perfluorosulfonic acids and perfluorooctyl sulfonamide at a wastewater treatment
      plant.
AB  - In situ measurements of air and water phases at a wastewater treatment plant
      (WWTP) were used to investigate the partitioning behavior of perfluorocarboxylic
      acids (PFCAs), perfluorosulfonic acids (PFSAs) and perfluorooctyl sulfonamide
      (HFOSA) and their conjugate bases (PFC(-)s, PFS(-)s, and FOSA(-), respectively).
      Particle-dissolved (Rd) and air-water (QAW) concentration ratios were determined
      at different tanks of a WWTP. Sum of concentrations of C4-12,14 PFC(A)s,
      C4,6,8,10 PFS(A)s and (H)FOSA were as high as 50 pg m(-3) (atmospheric gas
      phase), 2300 ng L(-1) (aqueous dissolved phase) and 2500 ng L(-1) (aqueous
      particle phase). Particle-dissolved concentration ratios of total species, log
      Rd, ranged from -2.9 to 1.3 for PFS(A)s, from -1.9 to 1.1 for PFC(A)s and was
      0.71 for (H)FOSA. These field-based values agree well with equilibrium
      partitioning data reported in the literature, suggesting that any in situ
      generation from precursors, if they are present in this system, occurs at a
      slower rate than the rate of approach to equilibrium. Acid QAW were also
      estimated. Good agreement between the QAW and the air-water equilibrium partition
      coefficient for C8PFCA suggests that the air above the WWTP tanks is at or near
      equilibrium with the water. Uncertainties in these QAW values are attributed
      mainly to variability in pKa values reported in the literature. The WWTP provides
      a unique environment for investigating environmental fate processes of the PFCAs
      and PFSAs under 'real' conditions in order to better understand and predict their
      fate in the environment.

PMID- 23561571
TI  - Toxicological evaluation of magnetic ionic liquids in human cell lines.
AB  - Magnetic ionic liquids (MILs) are new solvents with an interesting broad of
      applications however their toxicity is still an open issue. In this paper we
      report the toxicity of [C(8)MIM] and [Choline-C(n)] based magnetic ionic liquids
      assessed in two human cell lines: normal skin fibroblasts (CRL-1502) and
      colorectal adenocarcinoma cells (CaCo-2), acquiring this last characteristics of
      human enterocytes after differentiation. The results showed that [CoCl(4)] and
      [MnCl(4)] are more prone to generate cytotoxicity.

PMID- 23561572
TI  - Effects of polar oil related hydrocarbons on steroidogenesis in vitro in H295R
      cells.
AB  - Oil pollution from various sources, including exploration, production and
      transportation, is a growing global concern. Of particular concern is the
      environmental impact of produced water (PW), the main waste discharge from oil
      and gas platforms. In this study, we have investigated the potential of polar
      hydrocarbon pollutants to disrupt or modulate steroidogenesis in vitro, using a
      human adrenocortical carcinoma cell line, the H295R assay. Effects of two of the
      major groups of compounds found in the polar fraction of crude oil and PW;
      alkylphenols (C(2)- and C(3)-AP) and naphthenic acids (NAs), as well as the polar
      fraction of PW as a whole has been assessed. Endpoints include hormone (cortisol,
      estradiol, progesterone, testosterone) production at the functional level and key
      genes for steroidogenesis (17beta-HSD1, 17beta-HSD4, 3beta-HSD2, ACTHR, CYP11A1,
      CYP11B1, CYP11B2, CYP17, CYP19, CYP21, DAX1, EPHX, HMGR, SF1, STAR) and
      metabolism (CYP1A) at the molecular level. All compounds induced the production
      of both estradiol and progesterone in exposed H295R cells, while the C(3)-AP and
      NAs decreased the production of testosterone. Exposure to C(2)-AP caused an up
      regulation of DAX1 and EPHX, while exposure to NAs caused an up-regulation of
      ACTHR. All compounds caused an up-regulation of CYP1A1. The results indicated
      that these hydrocarbon pollutants, including PW, have the potential to disrupt
      the vitally important process of steroidogenesis.

PMID- 23561573
TI  - Evaluating population exposure to environmental pollutants during Deepavali
      fireworks displays using air quality measurements of the SAFAR network.
AB  - Indian government has implemented a state of art project "System of Air quality
      Forecasting And Research (SAFAR)" for assessing the air-quality scenario in Delhi
      during "Commonwealth Games-2010" which is operational in Delhi. Using a high
      resolution data of the SAFAR network, we estimate the excess numbers of cases for
      total, cardiovascular and respiratory mortalities and hospital admissions with
      the air-quality response to population attributable-risks due to emissions from
      fireworks displays (Deepavali-2010). The ratios of numbers of excess cases for
      fireworks displays (Deepavali) to those of non-Deepavali period (CWG-2010) vary
      from 1.75 to 3.5 for PM(2.5) and from 3 to 8 for PM(10) at monitoring stations in
      study area except in an airport. These ratios approach to 1 for PM(2.5) or PM(10)
      in airport area which can be attributed to restrictions on fireworks displays and
      eventually a very low population exposure. The numbers of excess cases for
      PM(2.5) and PM(10) during extreme emissions by fireworks displays are about 2
      fold to those of non-Deepavali period. The SAFAR is recognized by the Global
      Urban Research Meteorology and Environment of the World Meteorological
      Organization and thus results would likely to provide episodic limits for
      developing countries in common line with the air-quality standards set for
      developed world for pollutant levels due to emissions from the fireworks displays
      when population of country celebrates traditional festivals collectively.

PMID- 23561574
TI  - Reply to Comments on "Ozonation of a mixture of estrogens and progestins in
      aqueous solution: interpretation of experimental results by computational
      methods" by Ekaterina V. Rokhina, Nagarjuna S. Vattikonda, Candice Johnson,
      Rominder P.S. Suri [Chemosphere 89 (11) (2012) 1323-1329].

PMID- 23561575
TI  - Is there a place for pressure-support ventilation and high positive end
      expiratory pressure combined to alpha-2 agonists early in severe diffuse acute
      respiratory distress syndrome?
AB  - Acute respiratory distress syndrome (ARDS) is associated with a high mortality
      linked primarily to co-morbidities (sepsis, cardiac failure, multiple organ
      failure, etc.). When the lung is the single failing organ, quick resolution of
      ARDS should skip some complications arising from a prolonged stay in the critical
      care unit. In severe ARDS (PaO2/FIO2=P/F<100 with positive end-expiratory
      pressure (PEEP) >= 5 cm H2O), current recommendations are to intubate the trachea
      of the patient and use mechanical ventilation, low tidal volume, high PEEP, prone
      positioning and possibly neuromuscular blockade in association with intravenous
      sedation. Another strategy is possible. Firstly, spontaneous ventilation (SV)
      coupled with pressure support (PS) ventilation and high PEEP is possible from
      tracheal intubation onwards, with the possible exception of the short period
      following immediately tracheal intubation. Secondly, using alpha-2 adrenergic
      agonists (e.g. clonidine, dexmedetomidine) can provide first-line sedation from
      the beginning of mechanical ventilation, as they preserve respiratory drive,
      lower oxygen consumption and pulmonary hypertension and increase diuresis. Alpha
      2 agonists are to be supplemented, if appropriate, by drugs devoid of effect on
      respiratory drive (neuroleptics, etc.). The expected benefits would be to prevent
      acquired diaphragmatic weakness, accumulation of sedation, cognitive dysfunction,
      and presumably improved outcome. This hypothesis should be tested in a double
      blind randomized controlled trial.

PMID- 23561576
TI  - Expanding Panjabi's stability model to express movement: a theoretical model.
AB  - Novel theoretical models of movement have historically inspired the creation of
      new methods for the application of human movement. The landmark theoretical model
      of spinal stability by Panjabi in 1992 led to the creation of an exercise
      approach to spinal stability. This approach however was later challenged, most
      significantly due to a lack of favourable clinical effect. The concepts explored
      in this paper address and consider the deficiencies of Panjabi's model then
      propose an evolution and expansion from a special model of stability to a general
      one of movement. It is proposed that two body-wide symbiotic elements are present
      within all movement systems, stability and mobility. The justification for this
      is derived from the observable clinical environment. It is clinically recognised
      that these two elements are present and identifiable throughout the body in
      different joints and muscles, and the neural conduction system. In order to
      generalise the Panjabi model of stability to include and illustrate movement, a
      matching parallel mobility system with the same subsystems was conceptually
      created. In this expanded theoretical model, the new mobility system is placed
      beside the existing stability system and subsystems. The ability of both
      stability and mobility systems to work in harmony will subsequently determine the
      quality of movement. Conversely, malfunction of either system, or their
      subsystems, will deleteriously affect all other subsystems and consequently
      overall movement quality. For this reason, in the rehabilitation exercise
      environment, focus should be placed on the simultaneous involvement of both the
      stability and mobility systems. It is suggested that the individual's relevant
      functional harmonious movements should be challenged at the highest possible
      level without pain or discomfort. It is anticipated that this conceptual
      expansion of the theoretical model of stability to one with the symbiotic
      inclusion of mobility, will provide new understandings on human movement. The use
      of this model may provide a universal system for body movement analysis and
      understanding musculoskeletal disorders. In turn, this may lead to a simple
      categorisation system alluding to the functional face-value of a wide range of
      commonly used passive, active or combined musculoskeletal interventions. Further
      research is required to investigate the mechanisms that enable or interfere with
      harmonious body movements. Such work may then potentially lead to new and evolved
      evidence based interventions.

PMID- 23561577
TI  - Tumor-associated copy number changes in the circulation of patients with prostate
      cancer identified through whole-genome sequencing.
AB  - BACKGROUND: Patients with prostate cancer may present with metastatic or
      recurrent disease despite initial curative treatment. The propensity of
      metastatic prostate cancer to spread to the bone has limited repeated sampling of
      tumor deposits. Hence, considerably less is understood about this lethal
      metastatic disease, as it is not commonly studied. Here we explored whole-genome
      sequencing of plasma DNA to scan the tumor genomes of these patients non
      invasively. METHODS: We wanted to make whole-genome analysis from plasma DNA
      amenable to clinical routine applications and developed an approach based on a
      benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We
      performed whole-genome sequencing from plasma at a shallow sequencing depth to
      establish a genome-wide copy number profile of the tumor at low costs within 2
      days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns
      with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high
      coverage. After intensive testing of our approach with samples from 25
      individuals without cancer we analyzed 13 plasma samples derived from five
      patients with castration resistant (CRPC) and four patients with castration
      sensitive prostate cancer (CSPC). RESULTS: The genome-wide profiling in the
      plasma of our patients revealed multiple copy number aberrations including those
      previously reported in prostate tumors, such as losses in 8p and gains in 8q.
      High-level copy number gains in the AR locus were observed in patients with CRPC
      but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated
      3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments
      in these cases. In an index case multiregional sequencing of the primary tumor
      identified different copy number changes in each sector, suggesting multifocal
      disease. Our plasma analyses of this index case, performed 13 years after
      resection of the primary tumor, revealed novel chromosomal rearrangements, which
      were stable in serial plasma analyses over a 9-month period, which is consistent
      with the presence of one metastatic clone. CONCLUSIONS: The genomic landscape of
      prostate cancer can be established by non-invasive means from plasma DNA. Our
      approach provides specific genomic signatures within 2 days which may therefore
      serve as 'liquid biopsy'.

PMID- 23561578
TI  - Reliability and validity of the weight status and dietary intake measures in the
      COMPASS questionnaire: are the self-reported measures of body mass index (BMI)
      and Canada's food guide servings robust?
AB  - BACKGROUND: The COMPASS study is designed to follow a cohort of ~30,000 grade 9
      to 12 students attending ~60 secondary schools for four years to understand how
      changes in school characteristics (policies, programs, built environment) are
      associated with changes in youth health behaviours. Since the student-level
      questionnaire for COMPASS (Cq) is designed to facilitate multiple large-scale
      school-based data collections using passive consent procedures, the Cq is only
      comprised of self-reported measures. The present study assesses the 1-week (1 wk)
      test-retest reliability and the concurrent validity of the Cq measures for weight
      status and dietary intake. METHODS: Validation study data were collected from 178
      grade 9 students in Ontario (Canada). At time 1 (T1), participants completed the
      Cq and daily recoding of their dietary intake using the web-based eaTracker tool.
      After one week, (T2), students completed the Cq again, participants submitted
      their daily eaTracker logs and staff measured their height and weight. Test
      retest reliability of the self-reported (SR) weight status and dietary intake
      measures at T1 and T2, and the concurrent validity of the objectively measured
      and SR weight status and dietary intake measures at T2 were examined using
      intraclass correlation coefficients (ICC). RESULTS: Test-retest reliability for
      SR height (ICC 0.96), weight (ICC 0.99), and BMI (ICC 0.95) are considered
      substantial. The concurrent validity for SR height (ICC 0.88), weight (ICC 0.95),
      and BMI (ICC 0.84) are also considered substantial. The test-retest reliability
      for SR dietary intake for fruits and vegetables (ICC 0.68) and milk and
      alternatives (ICC 0.69) are considered moderate, whereas meat and alternatives
      (ICC 0.41), and grain products (ICC 0.56) are considered fair. The concurrent
      validity for SR dietary intake identified that fruits and vegetables (ICC 0.53),
      milk and alternatives (ICC 0.60), and grain products (ICC 0.41) are considered
      fair, whereas meat and alternatives (ICC 0.34) was considered slight.
      CONCLUSIONS: While the test-retest reliability of the measures used in this study
      were all high, the concurrent validity of the measures was considered acceptable.
      The results support the use of the self-reported COMPASS weight status and
      dietary intake measures for use in research where objective measures are not
      possible.

PMID- 23561579
TI  - Limit of detection and limit of quantification development procedures for
      organochlorine pesticides analysis in water and sediment matrices.
AB  - BACKGROUND: Reliable values for method validity of organochlorine pesticides
      determination were investigated, in water by solid phase extraction and in
      sediment by Soxhlet extraction, followed by gas chromatography equipped with an
      electron capture detector. Organochlorine pesticides are categorized as
      Persistent Organic Pollutants. Hence, critical decisions to control exposure to
      these chemicals in the environment are based on their levels in different media;
      it is important to find valid qualitative and quantitative results for these
      components. In analytical chemistry, internal quality procedures are applied to
      produce valid logical results. RESULT: In this study, 18 organochlorine
      pesticides were targeted for analysis and determination in water and river
      sediment. Experiments based on signal-to-noise ratio, calibration curve slope and
      laboratory fortified blank methods were conducted to determine the limits of
      qualification and quantification. The data were compared with each other. The
      limitation values, following Laboratory Fortified Blank, showed significant
      differences in the signal-to-noise ratio and calibration curve slope methods,
      which are assumed in the results for the sample concentration factor to be 1,000
      times in water and 10 times in sediment matrices. The method detection limit
      values were found to be between 0.001 and 0.005 MUg/L (mean of 0.002 +/- 0.001)
      and 0.001 and 0.005 MUg/g (mean of 0.001 +/- 0.001). The quantification limits
      were found to be between 0.002 and 0.016 MUg/L (mean of 0.006 +/- 0.004) and
      0.003 and 0.017 MUg/g (mean of 0.005 +/- 0.003 MUg/L) for water and sediment,
      respectively, based on the laboratory fortified blank method. Because of
      different slopes in the calibration methods, it was also found that the
      limitation values for some components from the internal standard were higher than
      from external standard calibration, because in the latter a factor for injection
      efficiency is applied for calibration. CONCLUSION: Technically, there are
      differentiations between detection limits for quality and quantity from component
      to component, resulting from noise, response factors of instruments and matrix
      interference. However, the calculation method is the cause of differentiation for
      each component of the different methods. The results show that for no matter what
      component, the relationship between these levels in different methods is
      approximately: Signal to Noise : Calibration Slope = 1:10. Therefore, due to
      different methods to determine LOD and LOQ, the values will be different. In the
      current study, laboratory fortified blank is the best method, with lower
      limitation values for Soxhlet and solid phase extraction of OCPs from sediment
      and water, respectively.

PMID- 23561581
TI  - Predictors of poor outcomes following deep infection after internal fixation of
      ankle fractures.
AB  - The development of deep infection following operative treatment of ankle
      fractures can have catastrophic consequences. The aim of this study was to
      identify factors predisposing to treatment failure of an infected ankle fracture.
      Out of 1923 consecutive ankle fracture operations we identified 97 patients with
      deep infection necessitating at least one surgical debridement. The outcome
      measure was a clinical failure or success of the treatment. Various parameters
      considered to predict clinical outcome were evaluated. Treatment failure occurred
      in 27% of patients with deep infection necessitating surgical debridement. The
      mean age of these patients was 54 years and the mean follow-up time was 22
      months. The variables that were independently associated with an increased risk
      of treatment failure included smoking, postoperative malreduction, hardware
      removal from an ununited fracture and the need for two or more additional
      debridements. Other significant risk factors included diabetes, alcohol abuse,
      high-energy injury, Danis-Weber type C fracture, multibacterial infection and
      ununited fracture at debridement. Our study showed that smoking, postoperative
      malreduction and hardware removal prior to fracture union were the most important
      factors predisposing to a permanent complication following an ankle fracture
      infection. We recommend that hardware be removed only after fracture union has
      been confirmed.

PMID- 23561580
TI  - A comparison of injuries to moped/scooter and motorcycle riders in Queensland,
      Australia.
AB  - BACKGROUND: The popularity of moped and motor scooter riding in Australia is
      increasing. However, there is a paucity of information about their safety,
      especially in comparison to motorcycle riding where riders require specific
      licensing, education and training. Given it is widely established that motorcycle
      riders are overrepresented in road injury statistics, consideration of moped and
      scooter riders as a sub-group of all motorcyclists is required for accurate
      understanding of injury patterns and the acute care needs of this group. METHOD:
      A comparison of demographic, injury and acute care characteristics between
      seriously injured moped/scooter riders and motorcycle riders was undertaken using
      data from the state-wide trauma registry in Queensland, Australia, from 2006 to
      2010. RESULTS: A total of 206 moped/scooter riders and 2667 motorcycle riders
      were identified. Motorcycle rider injury admissions significantly decreased over
      time (p<0.01), whereas no change was observed for injured moped/scooter riders.
      Moped/scooter riders sustained a greater percentage of head/neck (+8.6%), facial
      (+3.0%) and abdominal injuries (+2.3%), whereas motorcycle riders sustained a
      greater percentage of upper extremity (+4.0%), thoracic (+3.9%), spinal (+3.6%)
      and lower extremity injuries (+2.6%). There was no statistically significant
      difference in injury severity, length of acute hospital stay, admission to ICU or
      survival to discharge from acute care between injured moped/scooter riders and
      motorcycle riders. CONCLUSION: The results of this study suggest that riders of
      mopeds/scooters and motorcycles may have different injury patterns, but sustain
      similar overall injury severity. This analysis fills a gap in transport crash
      data, where there is limited information on the nature of injuries sustained.
      While moped-related injuries cannot be isolated in ICD-10 health coding, it is
      anticipated that ICD-11, due for release in 2015, may provide a moped-specific
      code; however, this will not address the issue of the apparent interchangeable
      use of the terms 'moped' and 'scooter' when reporting or documenting such
      injuries in health data systems including the medical record. Improved
      identification of moped-related cases in health data is required to increase
      potential for linkage across health and transport crash data, which may be used
      for further evaluation of injuries sustained by moped and scooter riders.

PMID- 23561582
TI  - Clinical and radiological outcome of percutaneous plating in extra-articular
      proximal tibia fractures: a prospective study.
AB  - BACKGROUND: Despite various techniques of fixation, proximal tibia fractures are
      associated with poor outcome and increased rates of complications. Minimal access
      and rigid fixation are the keys for optimal outcome in such fractures. Therefore,
      this study was designed to look for the clinical and radiological outcomes of
      percutaneous locked plating (PLP) in extra-articular proximal tibia fracture.
      METHODS: Between April 2008 and September 2010, 47 consecutive patients with 49
      proximal third extra-articular tibial fractures (29 closed and 20 open injuries)
      underwent PLP. The patients were followed up at 6 weeks, 3 months, 6 months and 1
      year. The union rate and complications of this fixation were evaluated. The
      clinico-radiological outcomes were assessed at 1 year of surgery. RESULTS: Four
      patients had infection in the postoperative period which needed repeated
      debridement, gentamycin bead application and prolonged antibiotic therapy. Three
      of these infective cases ended up with nonunion and needed cancellous bone
      grafting. All the remaining fractures united. The average time for union was 20
      weeks in closed and type I open fracture and 25 weeks in type II and III
      fractures. No neurovascular injury, hardware failure or loss of fixation was
      documented till the last follow-up. The mean range of knee joint movement was 119
      degrees . The average lower extremity functional score (LEFS) was 59 (74%). There
      were 10 cases of malunion (20.14%), with six varus/valgus and five
      procurvatum/recurvatum (one having both sagittal and coronal malunion)
      angulations. There were no statistical differences between patients with malunion
      and normal alignment with regard to knee range of motion and LEFS. CONCLUSION:
      Minimally invasive osteosynthesis using PLP in extra-articular proximal tibia
      fractures showed a promising result with minimal complications.

PMID- 23561583
TI  - Diagnostic and therapeutic challenges of isolated small bowel perforations after
      blunt abdominal injury in low income settings: analysis of twenty three new
      cases.
AB  - BACKGROUND: Isolated small bowel injury (ISBI) related to abdominal blunt trauma
      is rare. Timely diagnosis could be difficult, especially in the absence of modern
      imaging and laparoscopic facilities. The determinants of mortality under such
      circumstances are unclear. METHODS: This study presents twenty three cases of
      ISBI related to blunt abdominal injury identified between January 2005 and
      December 2009 in a level III Hospital in Limbe, Cameroon. Data were retrieved
      from an ongoing prospective study on injuries and augmented by analysis of
      individual patient's files. We analysed information regarding modalities of
      diagnosis, delay between injury and diagnosis, operative findings, treatment and
      outcome. RESULTS: The ages of our patients ranged from 7 to 38 years with a mean
      of 19 years. Thirteen patients were children below the age of 16. The most
      frequent mechanism of injury was a fall (n=11). Associated lesions were
      identified in 7 patients. Delay between injury and diagnosis was above 12h in 16
      patients. Fifteen cases were admitted with obvious signs of peritonitis. Erect
      chest X-ray identified a pneumoperitoneum in 11 of the 17 patients for whom it
      was requested. Most perforations were located in the ileum. A total of 7
      complications occurred in 5 patients. These included 4 cases of post-operative
      peritonitis. Two patients with at least one associated lesion died. CONCLUSION:
      ISBI is seldom suspected. This causes delay in diagnosis and most cases present
      with a diffuse peritonitis. Early diagnosis and management in low income
      environment is likely to be improved by a greater awareness of clinicians about
      this injury, serial clinical assessment and repeated erect chest X-ray, rather
      than sophisticated tools such as CT scan or laparoscopy.

PMID- 23561584
TI  - Two types of squalor: findings from a factor analysis of the Environmental
      Cleanliness and Clutter Scale (ECCS).
AB  - BACKGROUND: Most people who collect and hoard, and then have difficulty
      discarding items, do not live in squalor, even though accumulation of hoarded
      items can make cleaning very difficult. Commonly, people living in squalor
      accumulate garbage, but relatively few fulfill proposed criteria for "hoarding
      disorder." We examined the overlap between hoarding and squalor among people
      referred because of unacceptable living conditions. METHODS: Ongoing collection
      of data by a Squalor Project team, including ratings on the Environmental
      Cleanliness and Clutter Scale (ECCS), allowed (1) description of characteristics
      of cases and (2) examination of ratings of uncleanliness, and of the effect of
      accumulation of items or material on access within dwellings. Principal component
      analysis was used to examine latent variables underlying the ECCS. RESULTS: The
      mean age of the referred occupants (108 male, 95 female) was 61.9 years. The mean
      ECCS score in 186 rated cases was 18.5. Factor analysis of ECCS data showed a two
      factor solution as the most plausible. Factor 1, comprising seven squalor items,
      accounted for 33.7% of the variance. Factor 2 comprised reduced accessibility and
      accumulation of items of little value (variance 17.6%). Accumulation of garbage
      loaded equally on the two factors. High levels of squalor and/or accumulation
      were recorded in 105 (56%) of the 186 dwellings. One-third scored high on
      accumulation/hoarding, while 38% scored high on squalor; 15% scored high on both
      squalor and accumulation. A quarter of those scoring high on squalor scored low
      on hoarding/accumulation. CONCLUSIONS: The ECCS is useful when describing whether
      referred cases show high levels of squalor, hoarding, or both.

PMID- 23561585
TI  - In vitro schistosomicidal effects of aqueous and dichloromethane fractions from
      leaves and stems of Piper species and the isolation of an active amide from P.
      amalago L. (Piperaceae).
AB  - Dichloromethane and aqueous fractions from leaves and stems of Piper arboreum
      Aubl., P. aduncum L., P. amalago L., P. crassinervium H.B. & K., P.
      diospyrifolium Kunth, P. hispidum Sw. and P. xylosteoides (Kunth) Steud. were
      tested against adult worms of Schistosoma mansoni. The in vitro activity was
      evaluated in terms of mortality, number of separated worms and number of worms
      with reduced motor activity. Most dichloromethane fractions from all Piper
      species showed moderate schistosomicidal activity, but aqueous fractions were not
      active. The dichloromethane fraction of P. amalago leaves (at 100 MUg/ml) showed
      the highest activity, resulting in worm mortality, the separation of worm pairs
      and reduced motor activity. Chromatographic fractionation of the dichloromethane
      fraction of P. amalago leaves led to the isolation of its major compound, which
      was also tested against adults of S. mansoni. The isolated piperamide N-[7-(3',4'
      methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine, at 100 MU m, resulted
      in the mortality of all adult worms after 24 h of incubation. The findings
      suggest that species of Piper are potential sources of schistosomicidal
      compounds.

PMID- 23561586
TI  - Clinical features of patients with decompensated heart failure after the Great
      East Japan Earthquake.
AB  - The occurrence of heart failure (HF) and its clinical features after a great
      disaster have not been rigorously examined. We retrospectively examined the
      effect of the Great East Japan Earthquake on the occurrence of decompensated HF.
      The number of patients admitted for treatment of decompensated HF and their
      clinical features were compared between 2 periods, March 11, 2011 to September
      10, 2011 (after the earthquake) and the same period in the previous year. The
      number of admissions increased from 55 in 2010 to 84 in 2011. A comparison of the
      clinical features showed that the patients admitted after the earthquake had (1)
      older age (p = 0.031), (2) greater systolic blood pressure (p = 0.039), (3) a
      greater incidence of new-onset HF due to valvular heart disease (p = 0.040), (4)
      interruption of drugs (p = 0.001), (5) a greater incidence of infection (p =
      0.019), (6) greater B-type natriuretic peptide (p = 0.005) and C-reactive protein
      (p = 0.003) levels, (7) a lower estimated glomerular filtration rate (p = 0.048)
      and lower albumin levels (p = 0.021), and (8) a larger diameter of the inferior
      vena cava (p = 0.008). In conclusion, these results suggest that the earthquake
      increased the incidence of HF in association with high blood pressure,
      interruption of drugs, inflammation, malnutrition, and fluid retention. Taking
      appropriate measures to control blood pressure, nutritional status, and hygiene
      environment might decrease the occurrence of HF in future disasters.

PMID- 23561587
TI  - Usefulness of preprocedural levels of advanced glycation end products to predict
      restenosis in patients with controlled diabetes mellitus undergoing drug-eluting
      stent implantation for stable angina pectoris (from the Prospective ARMYDA-AGEs
      Study).
AB  - Diabetes mellitus (DM) remains the main predictor of restenosis rates and
      cardiovascular events following successful percutaneous coronary intervention
      (PCI) despite the use of drug-eluting stents (DES). HbA1c <6.0% is considered an
      index of optimized metabolic control in patients with DM, but several studies are
      downsizing its role in the clinical management of these patients. Increasing
      evidence points at the role of advanced glycation end products (AGEs) in
      restenosis pathogenesis independently on Hb1AC levels. Thus, we investigated the
      predictive value of preprocedural AGE levels for in-stent restenosis in a
      population of euglycaemic diabetic patients undergoing PCI with DES implantation.
      One hundred twenty-five consecutive patients with DM in optimized glycemic
      control admitted for stable angina pectoris and treated with elective DES
      implantation at a tertiary hospital were prospectively included. The primary end
      point of the ARMYDA-AGEs study was to compare rates of angiographic ISR at 6
      months after the intervention according to pre-PCI levels of AGEs. Secondary end
      points were the correlations of AGE levels with occurrence of periprocedural
      myocardial damage, major adverse cardiac events, and in-stent late loss at 6
      month control coronary angiography. AGE levels >17 MUM was found to be an
      independent predictor of ISR at 6 months and stent lumen loss. AGEs failed to
      predict occurrence of secondary endpoints. In conclusion, elevated AGE levels
      predict occurrence of in-stent restenosis after DES implantation in patients with
      DM on optimized glycemic control and might represent a dosable marker of adverse
      outcome after PCI.

PMID- 23561588
TI  - Daughter-mother tako-tsubo cardiomyopathy.
AB  - The investigators describe the occurrence of an episode of acute tako-tsubo
      cardiomyopathy in a 51-year-old woman, which was followed, only days later, by an
      episode of acute tako-tsubo cardiomyopathy in her 74-year-old mother. The mother
      and daughter had distinctly different left ventricular contraction patterns, yet
      the left anterior descending coronary artery distribution was similar, extending
      beyond the left ventricular apex in both women. In conclusion, this unusual
      scenario suggests a familial predisposition to tako-tsubo cardiomyopathy.
      Furthermore, the daughter's event may have contributed to (or triggered) the tako
      tsubo episode in her mother.

PMID- 23561589
TI  - Treatment assignment of high-risk symptomatic severe aortic stenosis patients
      referred for transcatheter AorticValve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) has become an option for patients
      with symptomatic severe aortic stenosis whose co-morbidities place them at high
      surgical risk. However, little is known regarding treatment allocation. From May
      2008 to May 2011, all high-risk patients with symptomatic severe aortic stenosis
      referred to an experienced single-center TAVI clinic were reviewed. A total of
      170 consecutive patients were evaluated. Of these, 58 (34%) were accepted for
      TAVI (mean age 81 +/- 8 years). Thirty-three patients (19%) were accepted for
      conventional aortic valve replacement (AVR; mean age 83 +/- 6 years). Sixty-two
      patients (37%) were treated conservatively (mean age 83 +/- 6 years). Seventeen
      patients (10%) died awaiting complete assessment. At 30 days, all-cause mortality
      was 10% in the TAVI group, 3% in the conventional AVR group, and 32% in the
      conservatively treated group. Multivariate-adjustment identified the absence of
      chronic obstructive pulmonary disease (hazard ratio 0.30, 95% confidence interval
      0.09 to 0.98, p <0.05) and the absence of frailty (hazard ratio 0.19, 95%
      confidence interval 0.07 to 0.55, p <0.01) as independent predictors of
      conventional AVR. In conclusion, of the high-risk patients with severe aortic
      stenosis referred for TAVI at a large single center, approximately 1/2 were
      accepted for intervention (conventional AVR or TAVI), and roughly 1/3 were
      treated conservatively.

PMID- 23561590
TI  - Two-year follow-up of outcomes of second-generation everolimus-eluting stents
      versus first-generation drug-eluting stents for stenosis of saphenous vein grafts
      used as aortocoronary conduits.
AB  - Second-generation everolimus-eluting stents (EESs) have demonstrated superiority
      in efficacy and safety compared with first-generation drug-eluting stents (DESs)
      in the treatment of native coronary artery lesions. The present study evaluated
      and compared the safety and efficacy of EESs and first-generation DESs in
      saphenous vein graft lesions. The EES group consisted of 88 patients with 96
      lesions, and the first-generation DES group consisted of 243 patients with 317
      lesions (sirolimus-eluting stents, n = 212; paclitaxel-eluting stents, n = 105).
      The end points included target lesion revascularization, target vessel
      revascularization, major adverse cardiovascular events (composite of all-cause
      death, myocardial infarction, and target vessel revascularization), and definite
      stent thrombosis at 2 years. The groups had similar baseline characteristics and
      graft ages (128.1 +/- 77.5 vs 132.4 +/- 90.8 months, p = 0.686). The EES group
      had more type C lesions and less embolic protection device use. The peak
      postprocedure values of creatinine kinase-MB and troponin I were similar between
      the 2 groups. Overall, major adverse cardiovascular events occurred in 18.2% of
      EES patients and 35.0% of first-generation DES patients (p = 0.003), mainly
      driven by a lower target vessel revascularization rate (6.8% vs 24.5%, p <0.001).
      The target lesion revascularization rate was lower in the EES group (1.1% vs
      11.6%, p = 0.005). Stent thrombosis was low and similar between the 2 groups (0%
      vs 0.8%, p = 1.000). On multivariate analysis, the type of DES implanted and
      graft age were the only independent predictors of major adverse cardiovascular
      events. In conclusion, the superiority of EESs compared with first-generation
      DESs shown in native artery lesions has been extended to saphenous vein graft
      lesions and should be considered as the DES of choice for this lesion type.

PMID- 23561591
TI  - Predictors of progression of recently diagnosed atrial fibrillation in REgistry
      on Cardiac Rhythm DisORDers Assessing the Control of Atrial Fibrillation
      (RecordAF)-United States cohort.
AB  - The progression of atrial fibrillation (AF) to a more sustained form is
      associated with increased symptoms and morbidity. The aims of the REgistry on
      Cardiac Rhythm DisORDers Assessing the Control of Atrial Fibrillation (RecordAF)
      United States (US) cohort study were to identify the risk factors of AF
      progression and the effects of management approaches. RecordAF is the first
      worldwide, 1-year observational study of the treatment of community-based
      patients with recent-onset AF. We assessed AF progression at 12 months in the US
      cohort. AF progression was defined as a change of AF to a more sustained form
      (either paroxysmal becoming persistent or permanent, or persistent becoming
      permanent). The US cohort included 955 patients, with mean age of 68.9 years;
      56.8% were men and 88.8% were white. At entry, 59.6% of patients were selected
      for rate-control and 40.4% for rhythm-control therapy. At 12 months, the
      management strategy was unchanged for 68.2% of the patients in the rate- and
      77.7% of the patients in the rhythm-control groups. Overall, AF progression had
      occurred in 18.6% of patients at 12 months. The progression rate was
      significantly greater in the rate-control (27.6%) than in the rhythm-control
      (5.8%) group (p <0.001). Progression to permanent AF occurred in 16.4% of
      patients. In addition to a rate-control strategy, older age, AF rhythm at entry,
      persistent AF at baseline, and a history of stroke or transient ischemic attack
      independently predicted AF progression. Rate control was associated with AF
      progression, with a propensity score adjusted odds ratio of 2.67 (p <0.001). In
      conclusion, rate control was the preferred treatment of recent-onset AF in the US
      but was associated with more AF progression than rhythm control.

PMID- 23561592
TI  - Clinical and immunological predictors of prognosis for Japanese patients with
      thymoma-associated myasthenia gravis.
AB  - There are no immunological markers to predict the prognosis of thymoma-associated
      myasthenia gravis (MG). Clinical and immunological factors associated with
      thymoma recurrence or MG relapse were examined by logistic analyses in 56
      Japanese patients with thymoma-associated MG. Patients with anti-Kv1.4 antibodies
      showed higher frequencies of thymoma recurrence and MG relapse compared to those
      without. Anti-Kv1.4 antibody, Masaoka stage 4, World Health Organization type B3,
      and adjuvant radiotherapy were associated with thymoma recurrence. Multivariate
      analyses showed that anti-Kv1.4 antibody was the only independent factor
      associated with MG relapse. Anti-Kv1.4 antibody is a useful predictor of the
      prognosis of thymoma-associated MG.

PMID- 23561593
TI  - MGMT repletion after treatment of glioblastoma cells with temozolomide and O6
      benzylguanine implicates NFkappaB and mutant p53.
AB  - The DNA repair enzyme O6-methylguanine methyltransferase (MGMT) is a major
      determinant of glioma resistance to alkylating agents. Several strategies have
      been used to induce sensitization to alkylator-based treatments, including the
      direct MGMT inhibitor O6-benzylguanine (BG). However, replenishment of MGMT is
      often observed after the withdrawal of combined schedules of temozolomide (TMZ)
      and BG, thus preventing further treatment efficacy. In this study we investigated
      the potential mechanisms of resistance to combination treatment with TMZ and BG
      in the MGMT-proficient, p53-mutated (mt p53) T98G glioblastoma (GBM) cell line,
      looking for an effect on nuclear factor kappa B (NFkappaB) and mt p53, which are
      both transcriptional regulators of MGMT. The administration of TMZ alone led to
      minimal inhibition of T98G cell viability which was, however, enhanced with the
      addition of BG. This effect coincided with reduced expression of MGMT protein and
      transcript levels, and a decrease in cellular amount of NFkappaB and mt p53.
      However, withdrawal of the drugs led to an increase in cell viability, which was
      in parallel with repletion of MGMT protein and transcript levels and was also
      accompanied by elevated protein levels of NFkappaB and mt p53. Overall, these
      results suggest that NFkappaB and mt p53 induction may be responsible for the
      failure of BG to induce prolonged inhibition of direct repair in TMZ co-treated
      GBM cells with mt p53 status. 

PMID- 23561595
TI  - [Epidemiology and prevention of nosocomial invasive infections by filamentous
      fungi and yeasts].
AB  - Knowledge of the epidemiology of invasive fungal diseases in health care settings
      helps to establish the action levels necessary for its prevention. A first step
      is to identify groups of patients at high risk of invasive fungal diseases,
      establish accurate risk factors, observing the periods of greatest risk, and
      analyze the epidemiological profile in genera and species, as well as the
      patterns of antifungal resistance. Secondly, mechanisms to avoid persistent
      exposure to potential fungal pathogens must be established, protecting areas and
      recommending measures, such as the control of the quality of the air and water
      inside and outside the hospital, and determining and promoting appropriate
      architectural designs of health institutions. Finally, apart from the correct
      implementation of these measures, the use of antifungal prophylaxis should be
      considered in selected patients at very high risk, following the guidelines
      published.

PMID- 23561594
TI  - Combining cancer immunotherapy and targeted therapy.
AB  - The ability to pharmacologically modulate key signaling pathways that drive tumor
      growth and progression, but do not negatively impact the function of lymphocytes,
      provides avenues for rational combinatorial approaches to improve the antitumor
      activity of tumor immunotherapies. Novel targeted agents can very specifically
      block oncogenic events in cancer cells, leading to a pro-apoptotic milieu and a
      potential increase in sensitivity to recognition and attack by cytotoxic T
      lymphocytes (CTLs). Furthermore, targeted pathway modulation in lymphocytes may
      change their function and have activating effects in some instances. When tested
      together with recently developed powerful tumor immunotherapies, such
      combinations may exploit the highly specific targeting of oncogenes with small
      molecule inhibitors to lead to high frequency of tumor regressions, and merge
      this benefit with the durable responses achievable with effective tumor
      immunotherapies.

PMID- 23561596
TI  - Synthesis and antifungal activities of novel nicotinamide derivatives containing
      1,3,4-oxadiazole.
AB  - BACKGROUND: Pant diseases in agriculture are extremely difficult to control,
      which bring about for billions of dollars in economic losses worldwide each year;
      Nicotinamide derivatives has attracted more and more attention in the field of
      pesticide due to their broad bioactivities. In an effort to discover new
      molecules with good antifungal activity, a series of nicotinamide derivatives
      containing 1,3,4-oxadiazole were synthesized and bio-assayed. RESULTS: Bioassays
      demonstrated that some of the title compounds exhibited favorable antifungal
      activities against Gibberella zeae, Fusarium oxysporum, and Cytospora
      mandshurica. compounds 7b, 7c, 8, 9a, 9b, and 9c displayed 46.4%, 39.6%, 53.0%,
      43.2%, 58.3%, 45.6% activities against G. Zeae, respectively; the activities of
      compounds 7a, 7b, 8, 9a, 9b, and 9c against F. oxysporum were 55.2%, 51.1%,
      58.9%, 63.2%, 53.3%, and 47.6%, respectively; whereas inhibitory rates of
      compounds 7a, 7b, 7c, 8, 9a, 9b, and 9c on C. mandshurica were 53.1%, 49.9%,
      44.9%, 52.8%, 59.8%, 54.5%, and 49.3%, respectively. CONCLUSION: A series of the
      novel nicotinamide derivatives containing 1,3,4-oxadiazole were synthesized and
      bio-assayed. The results of antifungal tests revealed that the synthesized
      nicotinamide derivatives possessed weakly to moderately antifungal activities
      against G. zeae, F. oxysporum, and C. mandshurica. Most of the synthesized
      compounds exhibited similar activities as (or higher than) these of hymexozol on
      their corresponding fungus, and compounds 7a, 8, 9a, and 9b showed considerable
      prospects for further optimization. Primary structure-activity relationships
      revealed that the introduction of the groups of 4-chloro-6-methyl on benzene, the
      hydrazone group containing N,N-dimethylamino, and acetyl at -NH2 could enhance
      the antifungal activity.

PMID- 23561597
TI  - Practice patterns of Canadian Ophthalmological Society members in cataract
      surgery - 2012 survey.

PMID- 23561598
TI  - Socioeconomic status as a risk factor for late presentation of glaucoma in
      Canada.

PMID- 23561599
TI  - Socioeconomic status as a risk factor for late presentation of glaucoma in
      Canada.
AB  - OBJECTIVE: To evaluate the effect of socioeconomic status on late presentation of
      glaucoma. DESIGN: Prospective, multicentre, cross-sectional study. PARTICIPANTS:
      Newly diagnosed open-angle glaucoma. METHODS: Eligible subjects with newly
      diagnosed open-angle glaucoma underwent a comprehensive ocular examination and
      were classified as mild, moderate, or advanced according to the Canadian
      Ophthalmological Society glaucoma guidelines. Socioeconomic status was estimated
      by linking the subjects' postal code to the median household income in the 2006
      Canadian population census at the level of dissemination areas. Five equal income
      groups ranging from the lowest to the highest income quintile were considered and
      compared regarding the frequency and proportion of moderate or advanced glaucoma.
      RESULTS: A total of 290 subjects were included in the analysis; 151 (52.1%) had
      mild, 79 (26.9%) moderate, and 60 (21.0%) advanced disease at initial diagnosis.
      Patients with newly diagnosed glaucoma were less likely to come from the poorest
      neighborhood areas (16.21%) when compared with an expected one fifth (20%) of
      patients presented in each of the 5 social economic groups (P = 0.56). Compared
      with people from the poorest neighborhood areas, people from the richest
      neighborhood areas had a marginally lower risk for having moderate or advanced
      glaucoma at first presentation (prevalence ratio 0.66, 95% confidence interval:
      0.43-1.02, P = 0.06). This association was stronger among those >=65 years old (P
      = 0.006). CONCLUSIONS: To the best of our knowledge, this is the first study in
      Canada to provide evidence that socioeconomic deprivation is associated with
      greater severity of glaucoma at presentation, specifically for those >=65 years
      old. Consideration should be given to targeting poor neighborhood areas for
      glaucoma education, screening, or both.

PMID- 23561600
TI  - Analysis of reasons for noncompliance with laser treatment in patients of
      diabetic retinopathy.
AB  - OBJECTIVE: To identify the underlying reasons for noncompliance among Chinese
      patients undergoing laser photocoagulation treatment for diabetic retinopathy
      (DR). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 262 patients
      with DR with indications for panretinal photocoagulation and focal laser
      treatment were recruited. METHODS: Those who did not complete the prescribed
      laser treatment were categorized into 2 types of defaulters: Type 1 defaulters
      were those who did not initiate laser treatment as scheduled; type 2 defaulters
      were those who did not complete the entire laser sessions, including terminating
      midterm or defaulting prompt supplement of laser treatment. A standardized
      questionnaire was given to the 2 types of defaulters to collect information about
      the reasons for noncompliance. Data were analyzed and subjected to chi(2) test or
      Fisher exact statistical tests. RESULTS: The noncompliance rate was 45.5%, which
      is significantly greater than some developed countries. Unawareness of the
      necessity for treatment and unawareness of the importance to complete treatment
      were 2 main reasons leading to noncompliance, representing 28.8% and 36.0%,
      respectively. Unawareness of the necessity for treatment and fear of laser
      treatment were more important for type 1 defaulters (29 vs 6 and 11 vs 0,
      respectively), whereas unawareness of completeness of laser treatment was
      overweighed in type 2 defaulters (27 vs 13 patients; all P<0.01). These results
      were likely related to the lack of knowledge about the potential consequences of
      DR, the underlying principle of laser treatment, and panretinal photocoagulation
      procedures. CONCLUSIONS: Developing appropriate education programs targeting
      specific reasons will help to improve the compliance in patients with DR.

PMID- 23561601
TI  - Congenital ptosis repair-surgical, cosmetic, and functional outcome: a report of
      162 cases.
AB  - OBJECTIVE: To evaluate the surgical and functional outcome of congenital ptosis
      repair and the anisometropic changes after surgical repair of ptosis to determine
      the potential contribution of anisometropia to the development of refractive
      amblyopia. METHODS: The clinical records of 162 children with congenital ptosis
      that had been surgically repaired between 1995 and 2006 at the Goldschleger Eye
      Institute were reviewed and analyzed for functional and cosmetic outcome, visual
      acuity status, and presence of amblyopia. RESULTS: A total of 162 patients (mean
      age, 10 months) underwent surgical ptosis repair, of whom 120 (74%) had
      unilateral and 42 (26%) had bilateral ptosis. The surgeries were levator
      resection (47.5%), frontalis suspension (46.3%), and Fasanella-Servat (7.4%).
      Good functional and cosmetic outcomes were achieved in 130 (80.2%) patients, with
      unilateral cases showing more postoperative asymmetry. The reoperation rate was
      10.4% (8/77) for levator resection, 29.3% (22/75) for frontalis suspension, and
      20% (2/10) for Fasanella-Servat. There were no significant differences in visual
      acuity, spherical equivalent, or mean cylinder at 90 degrees  between the ptotic
      eyes before and after surgery (P = 0.33, P = 0.83, and P = 0.65, respectively),
      and compared with the sound eyes (P = 0.66, P = 0.78, and P = 0.08,
      respectively). The mean astigmatism correction by vector analysis after ptosis
      surgery was 1.1+/-0.68 D. CONCLUSIONS: Congenital ptosis repair yields good
      functional and cosmetic outcome, although the reoperation rate is relatively high
      (19.8%). Congenital unilateral ptosis was not associated with any differences in
      anisometropia or astigmatism between the ptotic and sound eye.

PMID- 23561602
TI  - Voluntary blinking and use of 0.25% dye on fluorescein dye disappearance test.
AB  - OBJECTIVE: To evaluate the effect of voluntary blinking and use of diluted
      fluorescein dye on fluorescein dye disappearance test (FDDT) in terms of
      diagnostic ability and test time. DESIGN: Prospective, nonrandomized case series.
      PARTICIPANTS: Thirty-nine patients who visited Hadong Seoul Eye Clinic between
      April 2009 and September 2009. METHODS: All participants underwent FDDT and a
      lacrimal syringing test, and were divided into 2 groups according to the lacrimal
      syringing test results. FDDT was performed using 3 protocols: conventional FDDT
      (2% FDDT), FDDT with voluntary blinking (2% FDDTb), and FDDT with voluntary
      blinking using diluted fluorescein (0.25% FDDTb). The results were assessed by
      comparing initial tear meniscus height and those at 5 (2% FDDT) or 3 minutes (2%
      FDDTb, 0.25% FDDTb) after dye instillation. Results were considered "normal" when
      the tear meniscus decreased to less than 50% of its initial height, and "delayed"
      when it decreased to>=50%. In cases with a normal result, a half-period of dye
      disappearance was also recorded. RESULTS: Regarding diagnostic ability, the 0.25%
      FDDTb test had highest sensitivity and specificity among 3 protocols (100% and
      80%, respectively). The half-period of dye disappearance was 3.17+/-1.72 minutes
      for 2% FDDT, 1.82+/-0.64 minutes for 2% FDDTb, and 1.04+/-0.69 minutes for 0.25%
      FDDTb, and showed significant difference among 3 tests (P = 0.001). CONCLUSIONS:
      The FDDT with voluntary blinking using 0.25% fluorescein had comparable
      diagnostic ability with the conventional FDDT, and allowed the test time to be
      significantly reduced.

PMID- 23561603
TI  - Retinal function assessment of trypan blue versus indocyanine green assisted
      internal limiting membrane peeling during macular hole surgery.
AB  - OBJECTIVE: To compare multifocal electroretinography (mfERG) retinal function and
      the anatomical and visual outcomes of macular hole surgery performed with
      indocyanine green (ICG) or trypan blue (TB). DESIGN: Prospective, randomized
      study. PARTICIPANTS: Twenty-five eyes of 24 patients. METHODS: Patients underwent
      a pars plana vitrectomy with removal of the internal limiting membrane. In 14
      eyes, internal limiting membrane visualization during macular hole repair was
      performed using TB, and ICG was used in 11 eyes. The examination protocol
      (performed before surgery and at 3 weeks, 3 months, 6 months, and 12 months after
      surgery) included optical coherence tomography, mfERG (mfERG-103 hexagons), and
      assessment of best corrected visual acuity (BCVA) and contrast sensitivity (CS).
      RESULTS: Closure of macular hole was achieved in 100% of the cases. In the TB
      group, P1 amplitude and implicit time improved significantly at 12 months after
      surgery (P < 0.05), whereas in the ICG group, significant improvement occurred at
      both 6 (P < 0.05) and 12 months (P < 0.01). BCVA improved significantly in both
      groups at 6 and 12 months (P < 0.01). Both groups also showed a statistically
      significant CS improvement at spatial frequency of 6 cycles per degree (P = 0.01)
      1 year postoperatively. At 12 months, improvement of P1 amplitude and implicit
      time, BCVA, and CS was not different between groups. CONCLUSIONS: In this study,
      the use of TB or ICG appears to yield similar improvement in terms of BCVA, CS,
      and mfERG amplitude and implicit time changes at 12 months.

PMID- 23561604
TI  - Effect of artificial tears on automated visual field testing in patients with
      glaucoma and dry eye.
AB  - OBJECTIVE: To evaluate the effects of artificial tears on automated visual field
      (VF) testing in patients with glaucoma with dry eye syndrome. DESIGN: Prospective
      study. PARTICIPANTS: Fifty eyes of 50 patients with medically treated primary
      open-angle glaucoma (POAG) were recruited for this study. The patients were
      subdivided into 2 subgroups: those with dry eye syndrome (group I) and those
      without dry eye syndrome (group II). METHODS: Tear break-up time, Lissamine green
      staining, and Schirmer I test with topical anesthesia were performed in the same
      order in all patients. Ocular Surface Disease Index questionnaire was completed
      by the patients. All participants underwent automated perimetry using the 24-2
      SITA (Swedish interactive threshold algorithm) standard strategy before and after
      1-week treatment with a lubricating eye drop 4 times daily. VF results were
      compared before and after the treatment using Wilcoxon signed rank test, and Mann
      Whitney test was performed to compare the results of patients in groups I and II.
      RESULTS: Of the 50 patients, 25 (50%) were diagnosed with dry eye syndrome. No
      significant differences between both groups were found with respect to age (P =
      0.779) and glaucoma duration (P = 0.722). In patients with glaucoma with dry eye
      syndrome, there was a significant improvement in test duration, mean deviation,
      and the number of depressed points at probability level less than 0.5% and less
      than 1% in pattern deviation plots after the treatment (P< 0.05). CONCLUSIONS:
      The use of artificial tears in patients with glaucoma with dry eye syndrome
      decreased VF testing time and improved test results.

PMID- 23561605
TI  - Effects of subconjunctivally injected bevacizumab, etanercept, and the
      combination of both drugs on experimental corneal neovascularization.
AB  - OBJECTIVE: To compare the effect of subconjunctivally injected bevacizumab,
      etanercept and the combination of both drugs on experimental corneal
      neovascularization in rats. DESIGN: Experimental study. PARTICIPANTS: 28 male
      Wistar-Albino rats. METHODS: Right corneas of rats were cauterized by silver
      nitrate sticks. Rats were divided randomly and equally into 4 groups so that each
      group contained 7 subjects. Immediately after the cauterization, 0.05 ml normal
      saline was injected subconjunctivally in group 1 (control group); 0.05 ml (1.25
      mg) bevacizumab was injected subconjunctivally in group 2; 0.05 ml (1.25 mg)
      etanercept was injected subconjunctivally in group 3; 0.05 ml (1.25 mg)
      bevacizumab and 0.05 ml (1.25 mg) etanercept was injected subconjunctivally in
      group 4. The rats were euthanized on the 8th day, and digital photographs were
      obtained before the eyes were enucleated. The area of corneal neovascularization
      was calculated from digital photographs. Corneal sections were analyzed by
      histopathologically. RESULTS: The burn stimulus score was +1 or higher in all
      eyes. The difference of the neovascularization score between groups was found to
      be statistically significant (p = 0.001). The area of corneal neovascularization
      was 79.8% in group 1, 43.2% in group 2, 54.5% in group 3, and 34.8% in group 4.
      In group 4, corneal neovascularization was inhibited more than in the other
      groups. Histologic examination showed that the treatment groups had less
      neovascularization, inflammation, and fibroblast activity than the control group
      (p< 0.05). CONCLUSIONS: Our study has shown that etanercept does have some
      antiangiogenic and anti-inflammatory effects in treatment of corneal
      neovascularization. The combination of bevacizumab and etanercept may be a
      promising approach in the treatment of corneal neovascularization.

PMID- 23561606
TI  - Periocular Paederus dermatitis mimicking preseptal cellulitis.
AB  - OBJECTIVE: To introduce clinical and demographic characteristics of our patients
      with periocular Paederus dermatitis. DESIGN: Retrospective study. PARTICIPANTS:
      Thirteen patients diagnosed with periocular Paederus dermatitis. METHODS: We
      included patients who presented to our ophthalmology clinic with pain, hyperemia,
      and tenderness on the eyelids, and were diagnosed with Paederus dermatitis based
      on clinical characteristics on dermatologic and ophthalmologic evaluation. Mean
      age was 31.5 years, and 31% of patients were female. RESULTS: Subjective
      complaints included burning and epiphora in 85% and itching in 15% of the
      patients. Clinical findings on the eyelid skin were erythematous patches and
      plaques with multiple pustules (69%), erosions and bulla remnants on an
      erythematous base (7.7%), squamous and crusted patches and plaques (15%), and
      erythematous patches (7.7%). In 85% of the patients, similar lesions were
      detected on the other parts of the face. The treatment comprised wet dressings,
      weak steroid ointments for erythematous areas, and antibiotic ointments for
      crusted areas. Fifteen percent of the patients received methyl-prednisolone
      because they had significant periorbital edema. The lesions had improved in all
      patients at the 1-week visit after treatment. CONCLUSIONS: Paederus dermatitis
      should be considered in the differential diagnosis of periocular infections and
      preseptal cellulitis. Meticulous questioning is of utmost importance for correct
      diagnosis and may prevent unnecessary systemic antibiotic use.

PMID- 23561607
TI  - Cytomegalovirus retinitis in the absence of AIDS.
AB  - OBJECTIVE: The purpose of this study was to evaluate systemic and ophthalmic
      features associated with Cytomegalovirus (CMV) retinitis in immunocompetent
      patients. DESIGN: Retrospective chart review. PARTICIPANTS: Nine patients with
      CMV retinitis who were clinically immunocompetent at the time of diagnosis.
      METHODS: Retrospective chart review of patients evaluated at the Casey Eye
      Institute, University of Washington, Bascom Palmer Eye Institute and University
      of Toronto. IRB approval was obtained. Retrospective chart review of patients
      evaluated at the Casey Eye Institute, University of Washington, Bascom Palmer Eye
      Institute and University of Toronto. IRB approval was obtained. RESULTS: Seven of
      the nine patients in our series were 60 years of age or above. Three patients had
      intravitreal steroid and VEGF inhibitor injections in the preceding year in the
      affected eye. Five of the nine patients were initially misdiagnosed to have acute
      retinal necrosis (ARN) for which they were on Valacyclovir for a variable period
      of time. Seven patients had anterior chamber and eight had vitreous inflammation.
      Six of the nine patients exhibited vascular attenuation or obliteration. All
      patients showed improvement in retinitis within weeks following therapy with
      intravitreal foscarnet and/or ganciclovir and systemic valganciclovir.

PMID- 23561608
TI  - Re: Orbital sparganosis.

PMID- 23561609
TI  - Re: Orbital sparganosis. Author reply.

PMID- 23561610
TI  - Disease recurrence after intraarterial chemotherapy in 2 patients with adenoid
      cystic carcinoma of lacrimal gland.

PMID- 23561611
TI  - Acute retinal necrosis secondary to cytomegalovirus following successful
      treatment of cytomegalovirus anterior uveitis in an immunocompetent adult.

PMID- 23561612
TI  - Diffuse metastatic melanoma to the retina: a clinicopathologic report.

PMID- 23561613
TI  - Endonasal endoscopy for removing nasal chondromesenchymal hamartoma extending
      from the lacrimal sac region.

PMID- 23561614
TI  - Bilateral central retinal vein occlusion in multiple myeloma.

PMID- 23561615
TI  - Surgical embolectomy for central retinal artery occlusion.

PMID- 23561616
TI  - Laser goggles alter the perceived colour of drug labels, increasing the risk for
      drug errors.

PMID- 23561617
TI  - Intraocular cilium causing corneal endothelium cell deficiency.

PMID- 23561618
TI  - Two cases of corneal abrasions in children exposed to liquid detergent capsules.

PMID- 23561619
TI  - Bilateral diffuse scleritis as a first manifestation of immunoglobulin G4-related
      sclerosing pachymeningitis.

PMID- 23561620
TI  - Case of simultaneous bilateral anterior ischemic optic neuropathy associated with
      Takayasu disease.

PMID- 23561621
TI  - Intravenous rituximab for the treatment of cancer-associated retinopathy.

PMID- 23561622
TI  - Role of frozen section analysis of surgical margins during robot-assisted
      laparoscopic radical prostatectomy: a 2608-case experience.
AB  - It remains unanswered whether and how intraoperative frozen section analysis
      contributes to the surgical margin status on radical prostatectomy specimens. We
      aimed to determine whether frozen section analysis during radical prostatectomy
      reduces the incidence of positive surgical margins. We retrospectively analyzed a
      consecutive series of patients undergoing robot-assisted laparoscopic radical
      prostatectomy performed at our institution between 2004 and 2011. We identified
      2608 cases, including 1128 (43.3%) where intraoperative frozen section analysis
      was performed to assess surgical margins. Of the cases with positive (n = 60;
      5.3%)/negative (n = 1029; 91.2%)/atypical or indeterminate (n = 39; 3.5%) frozen
      section analyses, 22 (36.7%)/83 (8.1%)/4 (10.3%) were found to have positive
      surgical margins on radical prostatectomy specimens, respectively. Thus, 109
      (9.7%) of 1128 cases with frozen section analysis had positive surgical margins,
      compared with 163 (11.0%) of 1480 cases with no frozen section analysis (P =
      .264). When the patients were subgrouped by histopathologic characteristics,
      frozen section analysis led to a considerable reduction in the rate of positive
      surgical margins in cases with biopsy Gleason score 7 (12.4% -> 8.7%; P = .087)/8
      (28.6% -> 16.3%; P = .048)/>=7 (15.3% -> 10.1%; P = .012) tumor or pT3b (36.6% ->
      23.2%; P = .075)/>=pT3b (38.1% -> 25.4%; P = .091) disease. Multivariate analysis
      further revealed that performing frozen section analysis in biopsy Gleason score
      7 or higher tumors was an independent predictor of negative surgical margins
      (odds ratio, 0.61; P = .018). In addition, frozen section analysis of the distal
      urethra or apex of the prostate (7.5%, P = .035) as well as multiple negative
      frozen section analyses (>=2: 6.2%, P = .001; >=4: 2.2%, P = .007) correlated
      with significantly lower rates of positive surgical margin, compared with no
      frozen section analysis. Overall, intraoperative frozen section analysis did not
      dramatically change surgical margin status of radical prostatectomy. Nonetheless,
      it could be useful in preventing incomplete tumor resection, especially in men
      with high-grade (Gleason score >=7) tumor at the apex. 

PMID- 23561623
TI  - The prognostic value of tumor budding in invasive breast cancer.
AB  - We investigated the prognostic value of tumor budding in 160 cases of operable
      invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds
      was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of
      vision (200*). According to a cut-off score selected by ROC analysis, the cohort
      was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade
      budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test
      showed a good reproducibility with 0.717 as the K value. High-grade budding was
      significantly associated with the presence of lymphovascular invasion (LVI)
      (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By
      immunohistochemical staining, budded cells at the margin displayed epithelial
      mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative
      activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001)
      together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001),
      and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC
      NOS. In conclusion, tumor budding is a reproducible, significant, and independent
      histopathological prognostic factor in IDC-NOS.

PMID- 23561624
TI  - IDH1 mutation analysis in low cellularity specimen: a limitation of diagnostic
      accuracy and a proposal for the diagnostic procedure.
AB  - Recently, new techniques for detecting IDH1 mutations have been developed. Most
      studies assessed the mutation status in glioma tissue without consideration of
      the size of the samples. We assessed the mutation status of IDH1 in simulated
      small biopsied tissue from 5 low grade gliomas, prepared by grid cutting
      procedure with direct sequencing, IDH1 immunohistochemistry (IHC), multiplex PCR
      with single base extension (SBE) assay and PNA-clamping method, and then analyzed
      the agreement between the methods. Kappa values were 0.53 (direct sequencing),
      0.59 (multiplex PCR with SBE assay), and 0.69 (PNA-clamping method). Discrepant
      results between the methods were observed in lower cellularity samples. Twelve
      out of 25 cases were classified as wild type by direct sequencing, even with IDH1
      IHC-positive cells, whereas 6, 8, and 11 of IHC-negative cases were classified as
      mutant cases by other 3 methods. In conclusion, newly developed sensitive
      methods, such as the PNA-clamping method and multiplex PCR with SBE assay, are
      practically useful in addition to the conventional IDH1 IHC in small biopsied
      samples.

PMID- 23561627
TI  - Quality of life in dementia: the role of non-cognitive factors in the ratings of
      people with dementia and family caregivers.
AB  - BACKGROUND: The validity of self-reported quality-of-life (QoL) assessments of
      people with dementia (PWD) is a critical issue. We designed this study to
      determine the non-cognitive factors that are associated with self-reported QoL
      and PWD QoL as rated by family caregivers. METHODS: Using a cross-sectional
      study, we assessed QoL of 41 people with mild Alzheimer's disease (AD). The
      individuals with AD and their family caregivers completed the Quality of Life in
      Alzheimer's Disease Scale (QoL-AD), the Assessment Scale of Psychosocial Impact
      of the Diagnosis of Dementia (ASPIDD), the Mini-Mental State Examination (MMSE),
      the Clinical Dementia Rating (CDR) scale, the Cornell Scale for Depression in
      Dementia (CSDD), the Pfeffer Functional Activities Questionnaire (FAQ), and the
      Zarit Burden Interview (ZBI). Univariate and multivariate regression analyses
      were conducted to examine the contribution of the various cofactors. RESULTS: We
      observed a significant difference (t = 3.292, p < 0.01, d = 0.727) in the QoL
      measures of PWD after comparing self-reported assessments with the assessments of
      family caregivers. Linear regression analysis demonstrated that awareness of
      disease was related to PWD QoL-AD scores. Both the education levels of family
      caregivers and the depressive symptoms in PWD were related to the family
      caregivers' ratings of PWD QoL. CONCLUSIONS: The difference between self-reported
      QoL and family caregivers' ratings of QoL in people with mild dementia indicated
      that cognitive impairment was not the primary factor that accounted for the
      differences in the QoL assessments. Our findings suggested that non-cognitive
      factors, such as awareness of disease and depressive symptoms, played an
      important role in the differences between the self-reported AD QoL ratings and
      the caregivers' AD QoL ratings. A major implication is that discrete measures
      such as cognition or level of function are likely to miss important factors that
      influence QoL.

PMID- 23561628
TI  - The write stuff: how good writing can enhance patient care and professional
      growth.

PMID- 23561625
TI  - Extrapolating the effect of deleterious nsSNPs in the binding adaptability of
      flavopiridol with CDK7 protein: a molecular dynamics approach.
AB  - BACKGROUND: Recent reports suggest the role of nonsynonymous single nucleotide
      polymorphisms (nsSNPs) in cyclin-dependent kinase 7 (CDK7) gene associated with
      defect in the DNA repair mechanism that may contribute to cancer risk. Among the
      various inhibitors developed so far, flavopiridol proved to be a potential
      antitumor drug in the phase-III clinical trial for chronic lymphocytic leukemia.
      Here, we described a theoretical assessment for the discovery of new drugs or
      drug targets in CDK7 protein owing to the changes caused by deleterious nsSNPs.
      METHODS: Three nsSNPs (I63R, H135R, and T285M) were predicted to have functional
      impact on protein function by SIFT, PolyPhen2, I-Mutant3, PANTHER, SNPs&GO, PhD
      SNP, and screening for non-acceptable polymorphisms (SNAP). Furthermore, we
      analyzed the native and proposed mutant models in atomic level 10 ns simulation
      using the molecular dynamics (MD) approach. Finally, with the aid of Autodock 4.0
      and PatchDock, we analyzed the binding efficacy of flavopiridol with CDK7 protein
      with respect to the deleterious mutations. RESULTS: By comparing the results of
      all seven prediction tools, three nsSNPs (I63R, H135R, and T285M) were predicted
      to have functional impact on the protein function. The results of protein
      stability analysis inferred that I63R and H135R exhibited less deviation in root
      mean square deviation in comparison with the native and T285M protein. The
      flexibility of all the three mutant models of CDK7 protein is diverse in
      comparison with the native protein. Following to that, docking study revealed the
      change in the active site residues and decrease in the binding affinity of
      flavopiridol with mutant proteins. CONCLUSION: This theoretical approach is
      entirely based on computational methods, which has the ability to identify the
      disease-related SNPs in complex disorders by contrasting their costs and
      capabilities with those of the experimental methods. The identification of
      disease related SNPs by computational methods has the potential to create
      personalized tools for the diagnosis, prognosis, and treatment of diseases. LAY
      ABSTRACT: Cell cycle regulatory protein, CDK7, is linked with DNA repair
      mechanism which can contribute to cancer risk. The main aim of this study is to
      extrapolate the relationship between the nsSNPs and their effects in drug-binding
      capability. In this work, we propose a new methodology which (1) efficiently
      identified the deleterious nsSNPs that tend to have functional effect on protein
      function upon mutation by computational tools, (2) analyze d the native protein
      and proposed mutant models in atomic level using MD approach, and (3)
      investigated the protein-ligand interactions to analyze the binding ability by
      docking analysis. This theoretical approach is entirely based on computational
      methods, which has the ability to identify the disease-related SNPs in complex
      disorders by contrasting their costs and capabilities with those of the
      experimental methods. Overall, this approach has the potential to create
      personalized tools for the diagnosis, prognosis, and treatment of diseases.

PMID- 23561629
TI  - Total antioxidant capacity of diet and risk of heart failure: a population-based
      prospective cohort of women.
AB  - BACKGROUND: Few studies have investigated the association between individual
      antioxidants and risk of heart failure. No previous study has investigated the
      role of all antioxidants present in diet in relation to heart failure. The aim of
      this study was to assess the association between total antioxidant capacity of
      diet, which reflects all of the antioxidant compounds in food and the
      interactions between them, and the incidence of heart failure among middle-aged
      and elderly women. METHODS: In September 1997, 33,713 women (aged 49-83 years)
      from the Swedish Mammography Cohort completed a food-frequency questionnaire.
      Estimates of dietary total antioxidant capacity were based on the Oxygen Radical
      Absorbance Capacity assay measurements of foods. Women were followed for incident
      heart failure (hospitalization or mortality of heart failure as the primary
      cause) through December 2009 using administrative health registries. Cox
      proportional hazard models were used to calculate relative risks and 95%
      confidence intervals. RESULTS: During 11.3 years of follow-up (394,059 person
      years), we identified 894 incident cases of heart failure. Total antioxidant
      capacity of diet was inversely associated with heart failure (the multivariable
      adjusted relative risk in the highest quintile compared with the lowest was 0.58
      [95% confidence interval, 0.47-0.72; P for trend<.001]). The crude incidence rate
      was 18/10,000 person-years in the highest quintile versus 34/10,000 person-years
      in the lowest quintile. CONCLUSIONS: The total antioxidant capacity of diet, an
      estimate reflecting all antioxidants in diet, was associated with lower risk of
      heart failure. These results indicate that a healthful diet high in antioxidants
      may help prevent heart failure.

PMID- 23561630
TI  - Breast cancer screening: the paradigm shifts (finally).

PMID- 23561631
TI  - Beyond mammography: new frontiers in breast cancer screening.
AB  - Breast cancer screening remains a subject of intense and, at times, passionate
      debate. Mammography has long been the mainstay of breast cancer detection and is
      the only screening test proven to reduce mortality. Although it remains the gold
      standard of breast cancer screening, there is increasing awareness of
      subpopulations of women for whom mammography has reduced sensitivity. Mammography
      also has undergone increased scrutiny for false positives and excessive biopsies,
      which increase radiation dose, cost, and patient anxiety. In response to these
      challenges, new technologies for breast cancer screening have been developed,
      including low-dose mammography, contrast-enhanced mammography, tomosynthesis,
      automated whole breast ultrasound, molecular imaging, and magnetic resonance
      imaging. Here we examine some of the current controversies and promising new
      technologies that may improve detection of breast cancer both in the general
      population and in high-risk groups, such as women with dense breasts. We propose
      that optimal breast cancer screening will ultimately require a personalized
      approach based on metrics of cancer risk with selective application of specific
      screening technologies best suited to the individual's age, risk, and breast
      density.

PMID- 23561632
TI  - Incidence and outcomes of ventilator-associated tracheobronchitis and pneumonia.
AB  - BACKGROUND: Prolonged intubation with mechanical ventilation carries a risk for
      ventilator-associated respiratory infections manifest as tracheobronchitis or
      pneumonia. This study analyzed natural history, incidence, and outcomes of
      patients developing ventilator-associated tracheobronchitis and pneumonia.
      METHODS: We studied 188 mixed intensive care unit (ICU) patients intubated >=48
      hours for the development of tracheobronchitis defined as quantitative
      endotracheal aspirate >=10(5) cfu/mL plus at least 2 clinical criteria (fever,
      leukocytosis, or purulent sputum). Pneumonia was defined as microbiologic
      criteria for tracheobronchitis and a new and persistent infiltrate on chest
      radiograph. RESULTS: Airways of 41 (22%) patients became heavily colonized with a
      bacterial pathogen(s) at a concentration of >=10(5) cfu/mL. Tracheobronchitis
      developed in 21 (11%) study patients, of which 6 (29%) later progressed to
      pneumonia. Including these 6 patients, 28 (15%) study patients developed
      pneumonia. Multidrug-resistant pathogens were isolated in 39% of pneumonia
      patients. Patients with tracheobronchitis and pneumonia had significantly more
      ventilator days and longer stays in the ICU (P <=.02). CONCLUSIONS: Approximately
      one third of tracheobronchitis patients later developed pneumonia. Patients with
      tracheobronchitis or pneumonia experienced significantly more ventilator days and
      longer ICU stays, but had no difference in mortality. Better patient outcomes and
      reduced health care costs may be achieved by earlier treatment of ventilator
      associated respiratory infections, manifest as tracheobronchitis or pneumonia.

PMID- 23561634
TI  - Diarrhoea is not the only symptom that needs to be treated in patients with
      microscopic colitis.
AB  - BACKGROUND: Many patients with microscopic colitis (MC) also suffer from symptoms
      of irritable bowel syndrome (IBS), but the only treatment given is
      corticosteroids for the diarrhoea. The aim of this study was to examine how
      social factors, life style factors and drug treatment affect symptoms and well
      being in patients suffering from MC. METHODS: Women, over the age of 73years,
      with biopsy-verified MC, at any Departments of Gastroenterology, Skane, between
      2002 and 2010 were invited. The questionnaires Gastrointestinal Symptom Rating
      Scale (GSRS) and Psychological General Well-being Index (PGWB) were sent by mail,
      along with questions about social and life style factors, and medical history.
      RESULTS: Of 240 invited, 158 patients (66%) were included (median age 63years,
      range 27-73years). Only 26% had never smoked. Smoking and concomitant IBS were
      associated with both impaired gastrointestinal symptoms (OR=3.96, 95% CI=1.47
      10.66 and OR=4.40, 95% CI=2.09-9.26, respectively) and impaired psychological
      well-being (OR=2.77, 95% CI=1.04-7.34 and OR=3.82, 95% CI=1.83-7.99,
      respectively). Treatment with proton pump inhibitors (PPI) was associated with
      increased gastrointestinal symptoms (OR=3.44, 95% CI=1.45-8.16). Age, social
      factors, and corticosteroids had no effect on symptoms or well-being. Smoking was
      the only risk factor associated with IBS (OR=2.68, 95% CI=1.115-6.26).
      CONCLUSION: Smoking and IBS are associated with impaired gastrointestinal
      symptoms and psychological well-being in MC patients. PPI is associated with
      impaired gastrointestinal symptoms.

PMID- 23561633
TI  - Apoptosome structure, assembly, and procaspase activation.
AB  - Apaf-1-like molecules assemble into a ring-like platform known as the apoptosome.
      This cell death platform then activates procaspases in the intrinsic cell death
      pathway. In this review, crystal structures of Apaf-1 monomers and CED-4 dimers
      have been combined with apoptosome structures to provide insights into the
      assembly of cell death platforms in humans, nematodes, and flies. In humans, the
      caspase recognition domains (CARDs) of procaspase-9 and Apaf-1 interact with each
      other to form a CARD-CARD disk, which interacts with the platform to create an
      asymmetric proteolysis machine. The disk tethers multiple pc-9 catalytic domains
      to the platform to raise their local concentration, and this leads to zymogen
      activation. These findings have now set the stage for further studies of this
      critical activation process on the apoptosome.

PMID- 23561635
TI  - Mesenchymal stem cell transplantation to the mouse cochlea as a treatment for
      childhood sensorineural hearing loss.
AB  - OBJECTIVE: There is no treatment established for congenital sensorineural hearing
      loss because the majority of the cases are hereditary. Although congenital
      sensorineural hearing loss is thought to be hereditary, this hearing loss occur
      postnatally. We hypothesized that the transplantation of MSCs (mesenchymal stem
      cells) to the cochlea would be an effective therapy for stopping or delaying the
      progression of sensorineural hearing loss in childhood. METHODS: Cultured mouse
      MSCs were labeled with EGFP (enhanced green fluorescence protein) using
      retroviruses. EGFP-MSCs were transplanted into the posterior semicircular canal
      of mice at 2-3 weeks (young group) and 24-26 weeks (adult group) of age by a
      novel perilymphatic perfusion technique. Engraftment of MSCs was evaluated
      immunohistologically at 1 week and 2 weeks after transplantation. RESULTS: In
      young mice, migrated MSCs were detected in the cochlea tissue by
      immunofluorescence for EGFP and by immunohistochemistry for fibronectin. The
      differentiation of migrated MSCs into fibrocyte-like cells was demonstrated by
      immunofluorescence for connexin 26. There were no adverse effects on auditory
      function by MSC transplantation, and the auditory brain stem responses threshold
      did not significantly shift after surgery. In contrast, neither MSC migration nor
      differentiation was detected in the adult mice canal after MSC transplantation.
      CONCLUSION: The bone marrow derived MSCs were successfully transplanted into the
      cochlea of young mice by the perilymphatic perfusion technique and were further
      differentiated into fibrocyte-like cells without any adverse effects on auditory
      function.

PMID- 23561636
TI  - Efficacy of microbial cell preparation in improving chronic constipation: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND & AIMS: Probiotics is an emerging therapeutic agent which may
      alleviate the symptoms of constipation. We evaluated the effectiveness of
      microbial cell preparation (Hexbio((r))) containing fructooligosaccharide,
      Bifidobacterium and Lactobacillus in improving stool frequency and symptoms of
      chronic constipation. METHODS: A total of 120 constipated adults diagnosed using
      Rome III criteria were randomized and given either microbial cell preparation or
      placebo to be consumed twice daily. Follow-up was done after a 7-day intervention
      based on a questionnaire which includes an assessment of symptom profile and a
      stool diary. RESULTS: During the intervention period, the stool frequency was
      higher (p = 0.001) in the treatment group. Subjects experienced less straining (p
      = 0.001) and sensation of incomplete evacuation (p < 0.001), as well as improved
      stool consistency (p < 0.001) compared to the placebo group. While a higher
      proportion of subjects in the treatment group had a reduction in anorectal
      blockage sensation and having to defecate by manual maneuvers, the differences
      were not statistically significant. CONCLUSION: The results suggest that
      microbial cell preparation is effective in improving stool frequency and stool
      consistency. Furthermore, it could reduce the symptoms of straining and sensation
      of incomplete evacuation in adults with chronic functional constipation. MREC REG
      NO: 866.59 (IRB, UMMC, Malaysia).

PMID- 23561637
TI  - Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and
      glucose homeostasis in type 2 diabetic patients.
AB  - BACKGROUND & AIMS: Vitamin D supplementation has the potential to alleviate the
      cardiovascular damage in diabetic patients. The present study was designed to
      evaluate long term impact of high doses of vitamin D on arterial properties,
      glucose homeostasis, adiponectin and leptin in patients with type 2 diabetes
      mellitus. METHODS AND RESULTS: In randomized, placebo-controlled study 47
      diabetic patients were assigned into two groups: Group 1 received oral daily
      supplementation with vitamin D at a dose of 1000 U/day for 12 months. Group 2
      received matching placebo capsules. Blood sampling for metabolic parameters,
      including fasting glucose, lipid profile, HbA1C, insulin, hs-CRP, 25 OH Vit D,
      adiponectin and leptin was performed at baseline and at the end of the study.
      Insulin resistance was assessed by homeostasis model assessment (HOMA-IR).
      Central aortic augmentation index (AI) was evaluated using SphygmoCor. RESULTS:
      The two groups were similar at baseline in terms of hemodynamic parameters. After
      12 months, AI decreased significantly during the treatment period in patients
      received vitamin D (p < 0.0001) and did not change in placebo group. Glucose
      homeostasis parameters, leptin as well as leptin adiponectin ratio did not change
      in both groups. 25 OH Vit D level significantly increased (p = 0.022) and
      circulating adiponectin marginally increased (p = 0.065) during 12 month
      treatment period in active treatment and did not change in placebo group.
      CONCLUSIONS: High doses of vitamin D supplementation in diabetic patients was
      associated with significant decrease in AI during one year treatment. This
      beneficial vascular effect was not associated with improvement in glucose
      homeostasis parameters.

PMID- 23561638
TI  - Robot-assisted laparoscopic liver resection for hepatocellular carcinoma: short
      term outcome.
AB  - BACKGROUND: This study aimed at analyzing the perioperative and early survival
      outcomes of robotic liver resection of hepatocellular carcinoma (HCC). METHODS:
      The study population included a consecutive series of patients with HCC who
      underwent robotic liver resection at a single center. RESULTS: During the study
      period, 41 consecutive patients with HCC underwent 42 robotic liver resections.
      Five resections (11.9%) were carried out for recurrent HCC, and 23.8% (n = 10)
      were hemihepatectomy procedures. The mean operating time and blood loss was 229.4
      minutes and 412.6 mL, respectively. The R0 resection rate was 93%. The hospital
      mortality and morbidity rates were 0% and 7.1%, respectively. The mean hospital
      stay was 6.2 days. The 2-year overall and disease-free survival rates were 94%
      and 74%, respectively. In the subgroup analysis of minor liver resection, when
      compared with the conventional laparoscopic approach, the robotic group had
      similar blood loss (mean, 373.4 mL vs 347.7 mL), morbidity rate (3% vs 9%),
      mortality rate (0% vs 0%), and R0 resection rate (90.9% vs 90.9%). However, the
      robotic group had a significantly longer operative time (202.7 mins vs 133.4
      mins). CONCLUSIONS: This study demonstrated the feasibility and safety of robotic
      surgery for HCC, with favorable short-term outcome. However, the long-term
      oncologic results remain uncertain.

PMID- 23561639
TI  - A systematic review and meta-analysis evaluating the effectiveness of lightweight
      mesh against heavyweight mesh in influencing the incidence of chronic groin pain
      following laparoscopic inguinal hernia repair.
AB  - BACKGROUND: A systematic analysis was conducted of randomized controlled trials
      (RCTs) comparing lightweight mesh (LWM) with heavyweight mesh in laparoscopic
      inguinal hernia repair. METHODS: Data extracted from the included RCTs were
      analyzed according to the principles of meta-analysis. RESULTS: Eleven RCTs
      encompassing 2,189 patients were analyzed. In a fixed-effects model, operating
      time, postoperative pain, and recurrence rate were statistically similar between
      LWM and heavyweight mesh. LWM was associated with fewer perioperative
      complications and a reduced risk for developing chronic groin pain. There was
      also a reduced risk for developing other groin symptoms, such as foreign body
      sensations, but it was not statistically significant. CONCLUSIONS: The use of LWM
      for laparoscopic inguinal hernia repair is not associated with an increased risk
      for hernia recurrence. LWM reduces the incidence of chronic groin pain, groin
      stiffness, and foreign body sensations. Therefore, LWM may routinely be used in
      laparoscopic inguinal hernia repair. However, high-quality RCTs with longer
      follow-up periods are required to validate these findings.

PMID- 23561640
TI  - Alcohol use increases diagnostic testing, procedures, charges, and the risk of
      hospital admission: a population-based study of injured patients in the emergency
      department.
AB  - BACKGROUND: Alcohol use may alter mental status and vital signs in injured
      patients, leading to increased testing during emergency department (ED)
      evaluation. We hypothesized that alcohol use increases the hospital charges when
      caring for these injured patients. METHODS: The National Hospital Ambulatory
      Medical Care Survey collects weighted population-based estimates of ED use. We
      analyzed injury-related visits of adult patients, and resource use and admission
      rates were compared by the presence of alcohol. RESULTS: Alcohol was involved in
      6.0% of injury-related ED visits. Alcohol-present patients arrived by ambulance
      more frequently (45% vs 21%, P < .001), had a 26% longer ED stay (211 vs 167
      minutes, P < .001), and underwent more diagnostic testing. They were twice as
      likely to be admitted (14.0% vs 6.5%, P < .001). Additional ED charges were over
      $217 million. CONCLUSIONS: Patients with alcohol-related injuries use
      significantly more resources, with a significant added financial burden.
      Insurance companies in many states can deny coverage for injuries caused by
      alcohol use, shifting these expenses to trauma centers.

PMID- 23561641
TI  - The impact of adhesions on operations and postoperative recovery in colon cancer
      surgery.
AB  - BACKGROUND: Many surgeons assume that adhesions encountered during surgery
      negatively influence surgical outcomes. This article attempts to assess the role
      adhesions have on outcomes of colon cancer surgery. METHODS: Records of 1,071
      consecutive patients operated for colonic adenocarcinoma (2004-2011) were
      reviewed. Patients were assigned to 3 groups: no adhesions, any adhesions, or
      dense adhesions. Multivariate regression assessed the association between
      adhesions and the duration of surgery and stay as well as laparoscopic conversion
      and complication rates. RESULTS: Adhesions were encountered in 329 (30.7%)
      patients; 138 (12.8%) had dense adhesions. After correction for age and
      comorbidities, having adhesions was associated with longer surgeries (P < .001),
      longer hospital stays (P = .029), a borderline significantly higher conversion
      rate (P = .058), and a delayed return of bowel function (P = .037). Dense
      adhesions had stronger associations with surgical duration (P < .001), stay
      duration (P < .001), and conversion (P < .001). CONCLUSIONS: Abdominal adhesions
      independently put patients at risk for a longer and more complicated
      perioperative stay after colon cancer surgery.

PMID- 23561642
TI  - Incorporating the lessons learned from the 2012 East Azerbaijan Earthquakes in
      Iran's National Health Emergency Plan.

PMID- 23561643
TI  - Embryonic paratesticular rhabdomyosarcoma: a case report.
AB  - INTRODUCTION: An embryonic paratesticular rhabdomyosarcoma is a very rare
      mesenchymal tumor. It is an intrascrotal tumor that is localized in
      paratesticular structures such as the epididymis or spermatic cord.
      Rhabdomyosarcoma is most often observed in children and adolescents, presenting
      as a painless scrotal mass. CASE PRESENTATION: Our patient was an 18-year-old
      Moroccan man who presented with a painless left scrotal mass that had evolved
      over four months. An inguinal orchiectomy was performed. A histological
      examination of the excised tissue revealed an embryonic rhabdomyosarcoma.Our
      patient had three sessions of chemotherapy with vincristine, actinomycin C and
      cyclophosphamide. Each chemotherapy session was conducted over five days, with a
      cycle of 21 days. Our patient was assessed two months after the last chemotherapy
      session and demonstrated good clinical improvement. CONCLUSION: Paratesticular
      rhabdomyosarcoma is a rare aggressive tumor manifesting in children and very
      young adults. Localized forms have a good prognosis whereas metastatic tumors
      show very poor results. A well-defined treatment based on surgery and
      chemotherapy yields good results.

PMID- 23561644
TI  - Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in
      familial pancreatic cancer.
AB  - We sequenced 11 germline exomes from five families with familial pancreatic
      cancer (FPC). One proband had a germline nonsense variant in ATM with somatic
      loss of the variant allele. Another proband had a nonsense variant in PALB2 with
      somatic loss of the variant allele. Both variants were absent in a relative with
      FPC. These findings question the causal mechanisms of ATM and PALB2 in these
      families and highlight challenges in identifying the causes of familial cancer
      syndromes using exome sequencing.

PMID- 23561645
TI  - A MATLAB based orientation analysis of Acheulean handaxe accumulations in
      Olorgesailie and Kariandusi, Kenya Rift.
AB  - The Pleistocene archeological record in East Africa has revealed unusual
      accumulations of Acheulean handaxes at prehistoric sites. In particular, there
      has been intensive debate concerning whether the artifact accumulation at the
      Middle Pleistocene Olorgesailie (Southern Kenya Rift) and Kariandusi (Central
      Kenya Rift) sites were a result of fluvial reworking or of in situ deposition by
      hominids. We used a two-step approach to test the hypothesis of fluvial
      reworking. Firstly, the behavior of handaxes in water currents was investigated
      in a current flume and the flow threshold required to reorientate the handaxes
      was determined. The results of these experiments suggested that, in relatively
      high energy and non-steady flow conditions, handaxes will reorientate themselves
      perpendicular to the current direction. Secondly, an automated image analysis
      routine was developed and applied to archeological plans from three Acheulean
      sites, two at Olorgesailie and one at Kariandusi, in order to determine the
      orientations of the handaxes. A Rayleigh test was then applied to the orientation
      data to test for a preferred orientation. The results revealed that the handaxes
      at the Upper Kariandusi Site and the Olorgesailie Main Site Mid Trench had a
      preferential orientation, suggesting reworking by a paleocurrent. The handaxes
      from the Olorgesailie Main Site H/6A, however, appeared to be randomly oriented
      and in situ deposition by the producers therefore remains a possibility.

PMID- 23561646
TI  - Cilostazol protects vessels against hyperglycemic injury and accelerates healing
      after implantation of drug-eluting stent in a type 1 diabetes mellitus rat aorta
      stent model.
AB  - OBJECTIVE: Cilostazol, a selective phosphodiesterase-3 (PDE-3) inhibitor, can
      effectively suppress platelet activation and attenuate the increase in carotid
      intima-media thickness in diabetes mellitus (DM) patients. Therefore, we
      investigated whether cilostazol had effects on the healing process after
      implantation of a drug-eluting stent (DES) in a rat model of type 1 DM. METHODS
      AND RESULTS: Streptozotocin-induced DM rats were divided into 2 groups in which
      cilostazol (30 mg/kg/day; DM-Cilostazol) or vehicle (DM-Vehicle) was orally
      administered. Age-matched rats treated with the vehicle were used as a control
      group (NDM-Vehicle). After 4 weeks, cilostazol changed the expression of vascular
      cell adhesion molecule and intercellular adhesion molecule and the apoptotic cell
      ratio of the media (DM-Vehicle: 53.5 +/- 9.8%, DM-Cilostazol: 26.4 +/- 8.3%, p <
      0.05) in the aortic wall. Also, in a modified aortic ring test, cilostazol
      preserved the angiogenic potential of the aorta ([height of the sprouting tubes]
      DM-Vehicle: 0 +/- 0 MUm, DM-Cilostazol: 344.6 +/- 236.8 MUm, p < 0.05). After
      implantation of paclitaxel-eluting stents (PES) in rats treated with cilostazol
      or vehicle, thrombus formation, deposition of fibrin, and infiltration of
      inflammatory cells were attenuated by cilostazol. In particular, the re
      endothelialization by von Willebrand factor expression in the DM-PES-Cilostazol
      group was enhanced compared with that in the DM-PES-Vehicle group. CONCLUSION:
      Cilostazol has potential for protecting vessels against hyperglycemic injury and
      for accelerating the healing process after implantation of DES.

PMID- 23561648
TI  - Association of socioeconomic status, truncal fat and sICAM-1 with carotid intima
      media thickness in adolescents: the HELENA study.
AB  - OBJECTIVE: To measure the carotid intima-media-thickness (cIMT) and to assess its
      determinant factors in healthy adolescents. METHODS: 319 adolescents aged 12.5
      17.5 years (135 boys, 184 girls) were enrolled in this cross-sectional study.
      cIMT and carotid diameter were measured by high-resolution B-mode ultrasound.
      Anthropometric parameters, blood pressure, physical activity (PA), aerobic
      fitness and dietary intakes were assessed. Socioeconomic status was determined
      with the family affluence scale (FAS 4). Serum biological markers (lipids,
      glucose, high-sensitivity C-reactive protein, soluble adhesion molecules) were
      measured in a subsample of 96 adolescents. RESULTS: Multiple regression analysis
      showed that cIMT was positively associated with truncal fat (p = 0.021) and
      negatively with FAS 4 (p = 0.002) independently of age and blood pressure. There
      were no significant associations between cIMT and PA, fitness and dietary
      intakes. In the subsample soluble intercellular adhesion molecule 1 was
      positively correlated with cIMT (p = 0.017), independently of truncal fat, age
      and blood pressure. CONCLUSIONS: Low socioeconomic conditions and increased
      truncal fat are associated with greater carotid intima-media-thickness in
      adolescents.

PMID- 23561647
TI  - Genome-wide association study of coronary and aortic calcification implicates
      risk loci for coronary artery disease and myocardial infarction.
AB  - Arterial calcification is a well-known risk factor for coronary artery disease
      (CAD) and myocardial infarction (MI). We performed a genome-wide association
      study on coronary artery calcification and aortic calcification as intermediate
      traits for CAD/MI. We tested ~2.5 million SNPs for association with coronary
      artery calcification and aortic calcification in 2620 male individuals of the
      NELSON trial, who underwent chest CT scans. All participants were current or
      former heavy smokers. No SNPs were associated with aortic calcification on a
      genome-wide scale. The 9p21 locus was significantly associated with coronary
      artery calcification (rs1537370, P = 2.3 * 10(-11)). Since this locus corresponds
      to the strongest SNP association for CAD/MI, we tested 24 published and validated
      CAD/MI risk SNPs for association with arterial calcification. Besides the CAD/MI
      SNP at 9p21 (rs4977574, P = 3.1 * 10(-10)), two additional loci at ADAMTS7
      (rs3825807, P = 6.5 * 10(-6)) and at PHACTR1 (rs12526453, P = 1.0 * 10(-3)) show
      a nominally significant association with coronary artery calcification with
      MI/CAD risk alleles increasing the degree of arterial calcification. The 9p21
      locus was also nominally associated with aortic calcification (P = 3.2 * 10(-4)).
      These findings indicate that these CAD and MI risk loci are likely involved in
      arterial calcification.

PMID- 23561649
TI  - A comprehensive quality assurance program for personnel and procedures in
      radiation oncology: value of voluntary error reporting and checklists.
AB  - PURPOSE: This report describes the value of a voluntary error reporting system
      and the impact of a series of quality assurance (QA) measures including
      checklists and timeouts on reported error rates in patients receiving radiation
      therapy. METHODS AND MATERIALS: A voluntary error reporting system was instituted
      with the goal of recording errors, analyzing their clinical impact, and guiding
      the implementation of targeted QA measures. In response to errors committed in
      relation to treatment of the wrong patient, wrong treatment site, and wrong dose,
      a novel initiative involving the use of checklists and timeouts for all staff was
      implemented. The impact of these and other QA initiatives was analyzed. RESULTS:
      From 2001 to 2011, a total of 256 errors in 139 patients after 284,810 external
      radiation treatments (0.09% per treatment) were recorded in our voluntary error
      database. The incidence of errors related to patient/tumor site, treatment
      planning/data transfer, and patient setup/treatment delivery was 9%, 40.2%, and
      50.8%, respectively. The compliance rate for the checklists and timeouts
      initiative was 97% (P<.001). These and other QA measures resulted in a
      significant reduction in many categories of errors. The introduction of
      checklists and timeouts has been successful in eliminating errors related to
      wrong patient, wrong site, and wrong dose. CONCLUSIONS: A comprehensive QA
      program that regularly monitors staff compliance together with a robust voluntary
      error reporting system can reduce or eliminate errors that could result in
      serious patient injury. We recommend the adoption of these relatively simple QA
      initiatives including the use of checklists and timeouts for all staff to improve
      the safety of patients undergoing radiation therapy in the modern era.

PMID- 23561650
TI  - The interval to biochemical failure is prognostic for metastasis, prostate cancer
      specific mortality, and overall mortality after salvage radiation therapy for
      prostate cancer.
AB  - PURPOSE: To investigate the utility of the interval to biochemical failure (IBF)
      after salvage radiation therapy (SRT) after radical prostatectomy (RP) for
      prostate cancer as a surrogate endpoint for distant metastasis (DM), prostate
      cancer-specific mortality (PCSM), and overall mortality (OM). METHODS AND
      MATERIALS: A retrospective analysis of 575 patients treated with SRT after RP
      from a single institution. Of those, 250 patients experienced biochemical failure
      (BF), with the IBF defined as the time from commencement of SRT to BF. The IBF
      was evaluated by Kaplan-Meier and Cox proportional hazards models for its
      association with DM, PCSM, and OM. RESULTS: The median follow-up time was 85
      (interquartile range [IQR] 49.8-121.1) months, with a median IBF of 16.8 (IQR,
      8.5-37.1) months. With a cutoff time of 18 months, as previously used, 129 (52%)
      of patients had IBF <=18 months. There were no differences among any clinical or
      pathologic features between those with IBF <= and those with IBF >18 months. On
      log-rank analysis, IBF <=18 months was prognostic for increased DM (P<.0001, HR
      4.9, 95% CI 3.2-7.4), PCSM (P<.0001, HR 4.1, 95% CI 2.4-7.1), and OM (P<.0001, HR
      2.7, 95% CI 1.7-4.1). Cox proportional hazards models with adjustment for other
      clinical variables demonstrated that IBF was independently prognostic for DM
      (P<.001, HR 4.9), PCSM (P<.0001, HR 4.0), and OM (P<.0001, HR 2.7). IBF showed
      minimal change in performance regardless of androgen deprivation therapy (ADT)
      use. CONCLUSION: After SRT, a short IBF can be used for early identification of
      patients who are most likely to experience progression to DM, PCSM, and OM. IBF
      <=18 months may be useful in clinical practice or as an endpoint for clinical
      trials.

PMID- 23561652
TI  - Effects of treatment duration during concomitant chemoradiation therapy for
      cervical cancer.
AB  - PURPOSE: To determine whether extended treatment duration (TD) impacts in-field
      relapse and survival in the setting of concomitant chemoradiation therapy (CRT)
      for cervical cancer. METHODS AND MATERIALS: A total of 480 consecutive cervical
      cancer patients treated with radiation therapy (RT) alone or concomitant CRT for
      curative intent were retrospectively analyzed. Relapse was defined as in-field
      with respect to external beam radiation therapy fields. The effects of TD on in
      field relapse, disease-free survival (DFS), and overall survival (OS) rates were
      assessed continuously and categorically within the separate RT and CRT cohorts.
      Covariates included age, histology, stage, and cumulative dose to point A. In
      field relapse, DFS, and OS rates were estimated with Kaplan-Meier analysis;
      comparisons used log-rank statistic. Multivariate analysis used the Cox
      proportional hazards model. RESULTS: A total of 372 patients (RT n=206, CRT
      n=166) were evaluable, with a median follow-up for relapse-free patients of 4.2
      years (RT 4.4 years, CRT 4.2 years; P=.807). Treatment duration was longer in the
      RT cohort (median 55 days; range 35-99 days) versus the CRT cohort (median 51
      days; range 35-92 days) (P=.001). In the RT cohort, TD >=62 days trended to
      significance for predicting inferior DFS (hazard ratio 1.42, 95% confidence
      interval 0.86-1.98, P=.086). However, in the CRT cohort, TD assessed continuously
      or categorically across multiple cutoff thresholds did not predict for in-field
      relapse, DFS, or OS. CONCLUSION: With RT alone, extended TD >=62 days may
      adversely impact treatment efficacy. With the addition of concomitant
      chemotherapy to RT, however, extended TD has no effect on treatment efficacy.

PMID- 23561651
TI  - Multi-institutional prospective evaluation of bowel quality of life after
      prostate external beam radiation therapy identifies patient and treatment factors
      associated with patient-reported outcomes: the PROSTQA experience.
AB  - PURPOSE: To evaluate patients treated with external beam radiation therapy as
      part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment
      Quality Assessment (PROSTQA), to identify factors associated with posttreatment
      patient-reported bowel health-related quality of life (HRQOL). METHODS AND
      MATERIALS: Pretreatment characteristics and treatment details among 292 men were
      evaluated using a general linear mixed model for their association with measured
      HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years
      after enrollment. RESULTS: Bowel HRQOL had a median score of 100 (interquartile
      range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years,
      representing new moderate/big problems in 11% for urgency, 7% for frequency, 4%
      for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was
      the strongest predictor for all 2-year endpoints. In multivariable models, a
      volume of rectum >=25% treated to 70 Gy (V70) yielded a clinically significant
      9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P=.015) and
      predicted increased risks for moderate to big fecal incontinence (P=.0008). No
      other radiation therapy treatment-related variables influenced moderate to big
      changes in rectal HRQOL. However, on multivariate analyses V70 >=25% was
      associated with increases in small, moderate, or big problems with the following:
      incontinence (3.9-fold; 95% CI 1.1-13.4, P=.03), rectal bleeding (3.6-fold; 95%
      CI 1.3-10.2, P=.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P=.026).
      Aspirin use correlated with a clinically significant 4.7-point lower bowel
      summary score (95% CI 9.0-0.4, P=.03) and an increase in small, moderate, or big
      problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P=.018). Intensity
      modulated radiation therapy was associated with higher radiation therapy doses to
      the prostate and lower doses to the rectum but did not independently correlate
      with bowel HRQOL. CONCLUSION: After contemporary dose-escalated external beam
      radiation therapy up to 11% of patients have newly identified moderate/big
      problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to
      baseline function, rectal V70, and aspirin use. Finally, our findings validate
      the commonly utilized cut-point of rectal V70 >=25% as having significant impact
      on patient-reported outcomes.

PMID- 23561653
TI  - Pharmacotherapies for treating opioid use disorder.
AB  - Opioid use disorder (OUD) is a major public health problem in the United States.
      It has resulted in devastating consequences for people with this condition,
      including psychosocial and legal problems, in addition to contraction of
      infectious diseases such as HIV and hepatitis B and C. Furthermore, this disease
      can cause fatalities from drug overdoses and drug-drug interactions. OUD shatters
      families and destroys relationships. Effective treatment is crucial in order to
      curtail the consequences of this condition. The objective of this article is to
      provide a review of the pharmacotherapies currently being used to treat OUD. 

PMID- 23561654
TI  - High-throughput decoding of drug targets and drug resistance mechanisms in
      African trypanosomes.
AB  - The availability of genome sequence data has facilitated the development of high
      throughput genetic screening approaches in microbial pathogens. In the African
      trypanosome, Trypanosoma brucei, genome-scale RNA interference screens have
      proven particularly effective in this regard. These genetic screens allow for
      identification of the genes that contribute to a particular pathway or mechanisms
      of interest. The approach has been used to assess loss-of-fitness, revealing the
      genes and proteins required for parasite viability and growth. The outputs from
      these screens predict essential and dispensable genes and facilitate drug target
      prioritization efforts. The approach has also been used to assess resistance to
      anti-trypanosomal drugs, revealing the genes and proteins that facilitate drug
      uptake and action. These outputs also highlight likely mechanisms underlying
      clinically relevant drug resistance. I first review these findings in the context
      of what we know about current drugs. I then describe potential contributions that
      these high-throughput approaches could make to the development and implementation
      of new drugs.

PMID- 23561657
TI  - Recognition and management of transient ischaemic attack in primary care.

PMID- 23561656
TI  - Type 2 diabetes: prevention and cure?

PMID- 23561658
TI  - Multimorbidity: time for action rather than words.

PMID- 23561659
TI  - Enhancing consultations with interpreters: learning more about how.

PMID- 23561660
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561661
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561662
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561663
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561664
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561665
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561666
TI  - The case for neutrality on assisted dying - a personal view.

PMID- 23561667
TI  - The 2022 GP: our profession, our patients, our future.

PMID- 23561668
TI  - Tools.

PMID- 23561669
TI  - Making health habitual.

PMID- 23561670
TI  - Questionnaire survey of the effect of calorie labelling on consumers' cold drink
      purchases.

PMID- 23561671
TI  - Not just another primary care workforce crisis.

PMID- 23561672
TI  - Work and health reforms unattainable?

PMID- 23561673
TI  - Not just another primary care workforce crisis.

PMID- 23561674
TI  - Audit awareness among practices.

PMID- 23561675
TI  - ME/CFS and Blastocystis spp or Dientamoeba fragilis, an in-house comparison.

PMID- 23561676
TI  - Under-provision of medical care for vascular diseases for people with dementia in
      primary care: a cross-sectional review.
AB  - BACKGROUND: Vascular diseases contribute to the causation and progression of
      clinical dementia. AIM: To evaluate the quality of medical care for vascular
      diseases provided to people with dementia, the patient and practice
      characteristics that influence quality, and to compare care with that provided to
      those without dementia. DESIGN AND SETTING: Observational, cross-sectional review
      of primary care records of people with dementia from 52 general practices from
      five primary care trusts in the UK, and comparison with publicly available
      summary data on patients without dementia. METHOD: A total of 700 patients with
      >=1 diagnosed vascular disease or risk factor were identified from dementia
      registers. Quality of care was measured on 30 indicators from the UK Quality and
      Outcomes Framework (QOF) for hypertension, coronary heart disease, stroke,
      diabetes mellitus, atrial fibrillation, heart failure, and smoking. Overall
      quality of vascular care was calculated for each patient with dementia. RESULT:
      Level of care received by people with dementia was significantly lower compared
      with those without dementia for 22 of 30 (73%) indicators; most notably for
      measurement processes such as peripheral pulses check and neuropathy testing for
      diabetes, and cholesterol measures for stroke. Among people with dementia, women,
      those in care homes, and those with fewer comorbid physical conditions and
      medications were associated with lower scores for overall quality of vascular
      care. CONCLUSION: The quality of medical care provided to people with dementia
      with regard to vascular diseases is not concordant with quality, as defined by
      the QOF. Research is needed to improve access to high-quality care.

PMID- 23561677
TI  - Exercise and the Olympic bounce.

PMID- 23561678
TI  - First do no harm: the review frequency of illness depends as much on family
      dynamics as on material factors.

PMID- 23561679
TI  - Unsafety.

PMID- 23561680
TI  - Sport and exercise medicine: a hot topic thanks to the Olympics.

PMID- 23561682
TI  - An A-Z of medical philosophy: Bentham, Mill, and Utilitarianism.

PMID- 23561681
TI  - Inter-arm blood pressure differences compared with ambulatory monitoring: a
      manifestation of the 'white-coat' effect?
AB  - BACKGROUND: Inter-arm difference in blood pressure of >10 mmHg is associated with
      peripheral vascular disease, but it is unclear how much of the difference in
      sequential right and left arm blood pressure measurements might be due to a
      'white-coat' effect. AIM: To use ambulatory blood pressure monitoring (ABPM) to
      better understand the clinical significance of inter-arm differences in blood
      pressure. DESIGN AND SETTING: Retrospective study in a teaching hospital in
      Birmingham. METHOD: Anonymised clinical data collected from 784 patients
      attending a single hospital-based hypertension clinic were retrospectively
      analysed. Each participant had blood pressure measured sequentially in both arms,
      followed by ABPM over the subsequent 24 hours. RESULT: Data were available for
      710 (91%) patients, of whom 39.3% (279) had a blood pressure difference of 10
      mmHg or more between each arm. Compared to daytime systolic ABPM, the difference
      was 25.1 mmHg using the arm with the highest reading, but only 15.5 mmHg if the
      lower reading was taken (mean difference 9.6 mmHg (95% confidence interval [CI] =
      9.0 mmHg to 10.3 mmHg)). However, differences between mean right (20.7 mmHg) or
      left (19.9 mmHg) arm blood pressure and daytime systolic ABPM were very similar.
      CONCLUSION: Compared with ABPM, use of the higher of the left and right arm
      readings measured sequentially appears to overestimate true mean blood pressure.
      As there is no significant difference in the extent of disparity with ABPM by
      left or right arm, this is unlikely to be due to arm dominance and may be due to
      the 'white-coat' effect reducing blood pressure on repeated measurement. Where a
      large inter-arm blood pressure difference is detected with sequential
      measurement, healthcare professionals should re-measure the blood pressure in the
      original arm.

PMID- 23561683
TI  - GPwSIs and ITPs in general practice: a case study in gynaecology.

PMID- 23561685
TI  - Pearls: practical evidence about real life situations : limited evidence for
      exercise in smoking cessation.

PMID- 23561686
TI  - Changing practice with evidence-based aphorisms.

PMID- 23561687
TI  - Cognitive behavioural therapy: why primary care should have it all.

PMID- 23561688
TI  - Effectiveness of physical activity and dietary interventions in South Asian
      populations: a systematic review.
AB  - BACKGROUND: Physical activity and dietary change interventions can prevent or
      delay a range of chronic disease. Little is known in primary care about their
      effectiveness in South Asian populations, who are often at higher risk of
      developing such diseases. AIM: To assess evidence for effectiveness of primary
      care based physical activity and dietary interventions in South Asian
      populations, and identify methods to inform future intervention development.
      DESIGN: Systematic review. METHOD: Intervention studies conducted in developed
      countries that reported data for South Asian adults were sought by searching
      electronic databases, trial registries, and conference proceedings. Following
      wider screening of titles and abstracts, 119 full articles were reviewed. RESULT:
      Of the 119 articles, four studies met the inclusion criteria and evaluated
      community-based interventions with South Asian individuals. Methodological
      quality was poor overall. Interventions appeared generally effective in promoting
      a decrease in weight, with some positive changes in blood pressure and
      biochemical outcomes, such as cholesterol. There was limited evidence for effects
      on behaviour. Theoretical frameworks were not identified and evidence on
      attitudinal or knowledge-based outcomes was sparse. The inclusion of individual
      feedback and community workers in communities of deprivation appeared important
      to the acceptability of the interventions. Information distinguishable for South
      Asian individuals within intervention studies of general populations was lacking.
      CONCLUSION: Physical activity and dietary interventions with South Asian
      populations show modest promise but, given the paucity of controlled evaluations
      or use of objective measures, outcomes are difficult to interpret. Potential
      insights may be missed if experience concerning South Asian groups within studies
      is not reported. Further development of culturally appropriate interventions that
      are theoretically informed and assessed in experimental designs are required.

PMID- 23561689
TI  - Modern management of facial palsy: a review of current literature.

PMID- 23561690
TI  - Feasibility and indicative results from a 12-month low-energy liquid diet
      treatment and maintenance programme for severe obesity.
AB  - BACKGROUND: There is no established primary care solution for the rapidly
      increasing numbers of severely obese people with body mass index (BMI) > 40
      kg/m(2). AIM: This programme aimed to generate weight losses of >=15 kg at 12
      months, within routine primary care. DESIGN AND SETTING: Feasibility study in
      primary care. METHOD: Patients with a BMI >=40 kg/m(2) commenced a micronutrient
      replete 810-833 kcal/day low-energy liquid diet (LELD), delivered in primary
      care, for a planned 12 weeks or 20 kg weight loss (whichever was the sooner),
      with structured food reintroduction and then weight-loss maintenance, with
      optional orlistat to 12 months. RESULT: Of 91 patients (74 females) entering the
      programme (baseline: weight 131 kg, BMI 48 kg/m(2), age 46 years), 58/91(64%)
      completed the LELD stage, with a mean duration of 14.4 weeks (standard deviation
      [SD] = 6.0 weeks), and a mean weight loss of 16.9 kg (SD = 6.0 kg). Four patients
      commenced weight-loss maintenance omitting the food-reintroduction stage. Of the
      remaining 54, 37(68%) started and completed food reintroduction over a mean
      duration of 9.3 weeks (SD = 5.7 weeks), with a further mean weight loss of 2.1 kg
      (SD = 3.7 kg), before starting a long-term low-fat-diet weight-loss maintenance
      plan. A total of 44/91 (48%) received orlistat at some stage. At 12 months,
      weight was recorded for 68/91 (75%) patients, with a mean loss of 12.4 kg (SD =
      11.4 kg). Of these, 30 (33% of all 91 patients starting the programme) had a
      documented maintained weight loss of >=15 kg at 12 months, six (7%) had a 10-15
      kg loss, and 11 (12%) had a 5-10 kg loss. The indicative cost of providing this
      entire programme for wider implementation would be L861 per patient entered, or
      L2611 per documented 15 kg loss achieved. CONCLUSION: A care package within
      routine primary care for severe obesity, including LELD, food reintroduction, and
      weight-loss maintenance, was well accepted and achieved a 12-month-maintained
      weight loss of >=15 kg for one-third of all patients entering the programme.

PMID- 23561691
TI  - The challenge of communication in interpreted consultations in diabetes care: a
      mixed methods study.
AB  - BACKGROUND: The experience of diabetes care for individuals from minority ethnic
      groups, particularly individuals of Bangladeshi origin, shows they are at a
      significant disadvantage. AIM: To identify the challenges of interpreted
      consultations for healthcare providers and to explain the disadvantage
      experienced by patients from minority groups who have diabetes. DESIGN AND
      SETTING: Comparison of 12 interpreted consultations with 24 consultations
      involving fluent English speakers in four primary healthcare centres in Tower
      Hamlets, east London, UK. METHOD: Content analysis of video recordings of routine
      diabetes review consultations in primary care, involving 36 patients, nine nurses
      or healthcare assistants, and six interpreters. RESULT: Interpreted consultations
      were as long as same-language consultations but patients said less. The incidence
      of misunderstandings was similar but patients in interpreted consultations asked
      fewer questions. Indicators of social distance in interpreted consultations
      included less humour and less discussion of the patient's feelings or personal
      circumstances. Patients in interpreted consultations were less likely to raise
      issues unrelated to diabetes, to discuss their own ideas about health, or to talk
      about clinical parameters. Providers commonly addressed English-speaking patients
      directly but usually addressed patients through interpreters using the third
      person. Interpreters sometimes changed the meaning or did not translate speech,
      and they added their own comments. CONCLUSION: The findings explain some of the
      known problems of diabetes care for individuals from ethnic minorities. Effective
      training for interpreters and care providers is needed to reduce social distance
      and to facilitate patients' involvement in self-management.

PMID- 23561692
TI  - Quality-assured screening for diabetic retinopathy delivered in primary care in
      Ireland: an observational study.
AB  - BACKGROUND: At present, there is no national population-based retinopathy
      screening programme for people in Ireland who have diabetes, such as those
      operating in the UK for over a decade. AIM: To evaluate a community-based
      initiative that utilised existing resources in general practice and community
      optometry/ophthalmology services to provide screening for diabetic retinopathy.
      DESIGN AND SETTING: Cross-sectional study using electronic ophthalmic patient
      screening records in community optometry clinics in Cork, Ireland. METHOD: A
      purposive sample of 32 practices was recruited from Diabetes in General Practice,
      a general practice-led initiative in the South of Ireland. Practices invited all
      adult patients registered with diabetes to participate in free retinopathy
      screening (n = 3598), provided by 15 community optometry practices and two
      community ophthalmologists. Data were recorded on an electronic database used by
      optometrists and the performance was benchmarked against proposed national
      standards for retinopathy screening. RESULT: In total, 30 practices participated
      (94%). After 6 months, 49% of patients (n = 1763) had been screened, following
      one invitation letter and no reminder. Forty-three per cent of those invited
      consented to their data being used in the study and subsequent analyses are based
      on that sample (n = 1542). The mean age of the patients screened was 65 years
      (standard deviation = 13.0 years), 57% were male (n = 884), and 86% had type 2
      diabetes (n = 1320). In total, 26% had some level of retinopathy detected (n =
      395); 21% had background retinopathy (n = 331), 3% had pre-proliferative
      retinopathy (n = 53), and 0.7% had proliferative retinopathy (n = 11).
      CONCLUSION: The detection of retinopathy among 26% of those screened highlights
      the need for a national retinopathy screening programme in Ireland. Significant
      learning, derived from the implementation of this initiative, will inform the
      national programme.

PMID- 23561693
TI  - Musculoskeletal clinical assessment and treatment services at the primary
      secondary care interface: an observational study.
AB  - BACKGROUND: Management of musculoskeletal conditions in the UK is increasingly
      delivered in multidisciplinary clinical assessment and treatment services (CATS)
      at the primary-secondary care interface. However, there is little evidence
      concerning the characteristics and management of patients attending CATS. AIM: To
      describe the characteristics, investigation, and treatment of adults attending a
      musculoskeletal CATS. DESIGN AND SETTING: Cross-sectional analysis of cohort
      study baseline data from a musculoskeletal CATS in Stoke-on-Trent Primary Care
      Trust, UK. METHOD: All patients referred from primary care between February 2008
      and June 2009 were mailed a pre-consultation questionnaire concerning pain
      duration, general health status, anxiety, depression, employment status, and work
      absence due to musculoskeletal problems. At the consultation, clinical diagnoses,
      body region(s) affected, investigations, and treatment were recorded. RESULT: A
      total of 2166 (73%) completed questionnaires were received. Chronic pain duration
      >1 year (55%), major physical limitation (76%), anxiety (49%), and depression
      (37%) were common. Of those currently employed, 516 (45%) had taken time off work
      in the last 6 months because of their musculoskeletal problem; 325 (29%) were
      unable to do their usual job. The most frequent investigations were X-rays (23%),
      magnetic resonance imaging (18%), and blood tests (14%): 1012 (48%) received no
      investigations. Injections were performed in 282 (13%) and 492 (23%) were
      referred to physiotherapy. CONCLUSION: Although most patients presented with
      musculoskeletal problems suitable for CATS, chronic pain, physical limitation,
      anxiety, depression, and work disability were commonplace, highlighting the need
      for a biopsychosocial model of care that addresses psychological, social, and
      work-related needs, as well as pain and physical disability.

PMID- 23561694
TI  - Flurbiprofen microgranules for relief of sore throat: a randomised, double-blind
      trial.
AB  - BACKGROUND: Many people with sore throat seek, and are often inappropriately
      prescribed, antibiotics. AIM: The objective of this study was to determine the
      analgesic efficacy of flurbiprofen 8.75 mg microgranules versus placebo. These
      microgranules are a possible alternative treatment for patients with sore throat
      due to upper respiratory tract infection (URTI). DESIGN AND SETTING: Randomised,
      double-blind, placebo-controlled, multiple-dose study conducted at eight primary
      care sites in Australia. METHOD: Participants with sore throat of onset within
      the past 4 days received either flurbiprofen 8.75 mg microgranules or non
      medicated placebo microgranules. Throat soreness, difficulty in swallowing, sore
      throat pain intensity, sore throat relief, oral temperature, and treatment
      benefits were all assessed at regular intervals. RESULT: Of 373 patients from
      eight centres, 186 received flurbiprofen 8.75 mg microgranules and 187 received
      placebo microgranules (intent-to-treat population). Throat soreness was
      significantly reduced over the first 2 hours after the first dose. Reductions in
      difficulty in swallowing were observed at all time points from 5 to 360 minutes
      after the first dose, after taking flurbiprofen microgranules versus placebo.
      Sore throat relief was also evident at 1 minute and lasted for at least 6 hours.
      The multiple-dose efficacy results showed reduction of difficulty in swallowing
      at the end of days 1-3 and sore throat relief at the end of day 1. CONCLUSION:
      Microgranules containing flurbiprofen 8.75 mg provided fast and effective relief
      from sore throat due to URTI and represent an alternative treatment option to
      antibiotic therapy.

PMID- 23561695
TI  - Prevalence of urinary tract infection in acutely unwell children in general
      practice: a prospective study with systematic urine sampling.
AB  - BACKGROUND: Urinary tract infection (UTI) in children may be associated with long
      term complications that could be prevented by prompt treatment. AIM: To determine
      the prevalence of UTI in acutely ill children <= 5 years presenting in general
      practice and to explore patterns of presenting symptoms and urine sampling
      strategies. DESIGN AND SETTING: Prospective observational study with systematic
      urine sampling, in general practices in Wales, UK. METHOD: In total, 1003
      children were recruited from 13 general practices between March 2008 and July
      2010. The prevalence of UTI was determined and multivariable analysis performed
      to determine the probability of UTI. RESULT: Out of 597 (60.0%) children who
      provided urine samples within 2 days, the prevalence of UTI was 5.9% (95%
      confidence interval [CI] = 4.3% to 8.0%) overall, 7.3% in those < 3 years and
      3.2% in 3-5 year olds. Neither a history of fever nor the absence of an
      alternative source of infection was associated with UTI (P = 0.64; P = 0.69,
      respectively). The probability of UTI in children aged >=3 years without
      increased urinary frequency or dysuria was 2%. The probability of UTI was >=5% in
      all other groups. Urine sampling based purely on GP suspicion would have missed
      80% of UTIs, while a sampling strategy based on current guidelines would have
      missed 50%. CONCLUSION: Approximately 6% of acutely unwell children presenting to
      UK general practice met the criteria for a laboratory diagnosis of UTI. This
      higher than previously recognised prior probability of UTI warrants raised
      awareness of the condition and suggests clinicians should lower their threshold
      for urine sampling in young children. The absence of fever or presence of an
      alternative source of infection, as emphasised in current guidelines, may not
      rule out UTI in young children with adequate certainty.

PMID- 23561696
TI  - Diagnosing type 2 diabetes and identifying high-risk individuals using the new
      glycated haemoglobin (HbA1c) criteria.

PMID- 23561697
TI  - Management of patients presenting with otorrhoea: diagnostic and treatment
      factors.

PMID- 23561698
TI  - Resveratrol inhibits the deleterious effects of diet-induced obesity on thymic
      function.
AB  - Obesity is associated with an increased risk of infectious diseases. It has been
      shown to have deleterious effects on cell-mediated immunity, including reducing
      thymocyte numbers and altering responses of thymocytes to pathogens. In the
      current study, we examined the efficacy of the antiobesity phytochemical
      resveratrol in preventing the deleterious effects of a high-fat diet on thymic
      anatomy and function. Compared to C57Bl/6 male mice fed a low-fat diet, mice on a
      high-fat diet had a significant increase in thymic weight and lipid content, and
      a disrupted anatomy, including a reduction of the medullary compartment and
      absence of a corticomedullary junction. There were a decrease in thymic
      cellularity and mature T-cell output, and a disrupted T-cell maturation, as
      evidenced by increased double-negative and decreased single- and double-positive
      thymocytes. Mice that had been fed resveratrol along with a high-fat diet had a
      dose-dependent reversal in all these parameters. Western blots from thymi showed
      that obese mice had lower levels of the key stimulators of lipid metabolism,
      phospho-5' adenosine monophosphate-activated protein kinase and its downstream
      target, carnitine palmitoyl transferase-1; this was restored to normal levels in
      resveratrol-fed mice. Resveratrol also reversed an increase in glycerol-3
      phosphate acyltransferase-1, the enzyme that catalyzes the first step in
      triglycerol synthesis. Taken together, these results indicate that resveratrol is
      a potent inhibitor of the deleterious effects of diet-induced obesity on thymic
      anatomy and function, and this may hold promise in preventing obesity-related
      deficits in cell-mediated immunity. 

PMID- 23561699
TI  - [Cardiac troponin I and the post-mortem diagnosis of myocardial damage].
AB  - The aim of this study is to analyse the diagnostic efficacy of post-mortem dosage
      of cardiac troponine I in cadaver fluids in detection of myocardial damage.
      MATERIAL AND METHODS: Our study is prospective, interesting 72 corps autopsied at
      the Department of Forensic Medicine of the University Hospital Fattouma Bourguiba
      of Monastir-Tunisia. Were excluded from the study, resuscitated cases and those
      examined more than 48h after death. Levels of cardiac troponine I were measured
      in pericardial fluid, cardiac blood and peripheral blood. Statically significant
      correlations between different variables levels of cardiac troponine I and
      cardiac damage were studied. Receiver-operator characteristic (ROC) curves were
      generated and areas under the curves were determined. SPSS (version 12.0) et
      MedCalc statistical software (version 11.0) were used for statistical analysis.
      Results were considered to be statistically significant when P<0.05. MAIN
      RESULTS: Cardiac troponin I levels in pericardial fluid, cardiac and peripheral
      blood are correlated significantly between subject with and without observable
      signs of myocardial damage with a P value respectively at 0.0007, 0.0009 and
      0.004. ROC curves analysis showed that the pericardial fluid have the best
      sensibility and specificity with a cut-off level at 108ng/ml and an area under
      the curve at 0.925. CONCLUSION: Our data indicate that cardiac troponin I may be
      a powerful aid in the diagnosis of myocardial damages. This biological test can
      be used in triaging sudden deaths before to external examination versus complete
      autopsy.

PMID- 23561700
TI  - Should furosemide be avoided in acute right ventricular myocardial infarction?
AB  - BACKGROUND: Diuretics are conventionally prohibited in acute right ventricular
      myocardial infarction. AIMS: To assess the benefit of diuretics compared to fluid
      expansion in patients with inferior myocardial infarction extended to the right
      ventricule. METHODS: Of 295 patients admitted for inferior or posterior acute
      myocardial infarction between November 2008 and November 2010, 77 had a right
      ventricular extension. Among these 77 patients, 19 presented with oligoanuria
      (<0.5 mL/kg per hour) and no criteria for cardiogenic shock. Overall, 11 patients
      were treated by low dose of furosemide (40 to 80 mg) and eight received fluid
      expansion using isotonic saline solution. RESULTS: Baseline right ventricular
      dilatation and dysfunction, systolic blood pressure and heart rate were similar
      between the groups. Twenty-four hours after treatment, urine output was similar
      between the two groups but only the patients in the diuretic group improved their
      blood pressure (103 +/- 16 mmHg versus 127 +/- 20 mmHg, P < 0.001), heart rate
      (71 +/- 15 bpm versus 76 +/- 13 bpm, P = 0.03), creatinin level and alanine
      aminotrasferase plasmatic level. Hospitalization duration and the need of
      inotropic support were similar in the two groups. CONCLUSIONS: Diuretics and
      fluid expansion provide similar efficiency for triggering diuresis in patients
      with right ventricular infarction and oligoanuria but only diuretics seem to be
      associated with improvement in hemodynamic status and venous congestion.

PMID- 23561701
TI  - Genetic effects of ATP1A2 in familial hemiplegic migraine type II and animal
      models.
AB  - Na(+)/K(+)-ATPase alpha 2 (Atp1a2) is an integral plasma membrane protein
      belonging to the P-type ATPase family that is responsible for maintaining the
      sodium (Na(+)) and potassium (K(+)) gradients across cellular membranes with
      hydrolysis of ATP. Atp1a2 contains two subunits, alpha and beta, with each having
      various isoforms and differential tissue distribution. In humans, mutations in
      ATP1A2 are associated with a rare form of hereditary migraines with aura known as
      familial hemiplegic migraine type II. Genetic studies in mice have revealed other
      neurological effects of Atp1a2 in mice including anxiety, fear, and learning and
      motor function disorders. This paper reviews the recent findings in the
      literature concerning Atp1a2.

PMID- 23561702
TI  - Memantine treatment for neuropsychiatric symptoms in a patient with probable
      idiopathic normal pressure hydrocephalus: a case report.
AB  - INTRODUCTION: Patients with idiopathic normal pressure hydrocephalus often show
      neuropsychiatric symptoms besides the triad of 'classic' symptoms. Memantine has
      been reported to have positive effects on the neuropsychiatric symptoms of
      patients with Alzheimer's disease and patients with dementia with Lewy bodies. We
      administered memantine to a Japanese patient with probable idiopathic normal
      pressure hydrocephalus, hoping that this treatment would have positive effects on
      the neuropsychiatric symptoms of his idiopathic normal pressure hydrocephalus.
      CASE PRESENTATION: An 80-year-old right-handed Japanese man was diagnosed as
      having probable idiopathic normal pressure hydrocephalus and showed
      neuropsychiatric symptoms as well as the triad of classic symptoms of idiopathic
      normal pressure hydrocephalus. We treated our patient with memantine by
      increasing, decreasing, and then again increasing the dose of memantine. We
      evaluated his neuropsychiatric symptoms using the Neuropsychiatric Inventory at
      baseline, after the dose was increased to 20mg/day, after the dose was decreased
      to 5mg/day, and after the dose was increased again to 15mg/day. We simultaneously
      evaluated the triad of symptoms and conducted neuropsychological tests. In
      addition, we evaluated the psychological distress of our patient's caregiver
      using the Zarit Caregiver Burden Interview. CONCLUSIONS: Memantine had positive
      effects on the neuropsychiatric symptoms of our patient with idiopathic normal
      pressure hydrocephalus. Although none of his triad of classic symptoms, including
      cognitive abilities, improved, the psychological distress of our patient's
      caregiver improved.

PMID- 23561703
TI  - A patient-specific, finite element model for noncommunicating hydrocephalus
      capable of large deformation.
AB  - A biphasic model for noncommunicating hydrocephalus in patient-specific geometry
      is proposed. The model can take into account the nonlinear behavior of brain
      tissue under large deformation, the nonlinear variation of hydraulic conductivity
      with deformation, and contact with a rigid, impermeable skull using a recently
      developed algorithm. The model was capable of achieving over a 700 percent
      ventricular enlargement, which is much greater than in previous studies,
      primarily due to the use of an anatomically realistic skull recreated from
      magnetic resonance imaging rather than an artificial skull created by offsetting
      the outer surface of the cerebrum. The choice of softening or stiffening behavior
      of brain tissue, both having been demonstrated in previous experimental studies,
      was found to have a significant effect on the volume and shape of the deformed
      ventricle, and the consideration of the variation of the hydraulic conductivity
      with deformation had a modest effect on the deformed ventricle. The model
      predicts that noncommunicating hydrocephalus occurs for ventricular fluid
      pressure on the order of 1300 Pa.

PMID- 23561704
TI  - Predictors of short-term improvement of ischemic stroke.
AB  - OBJECTIVES: Several studies have sought factors predictive of early neurological
      deterioration during acute stroke; however, no study carried out a systematic
      search for factors capable of predicting early improvement. This investigation is
      aimed at identifying the variables associated with short-term neurological
      improvement in patients with ischemic stroke not undergoing thrombolysis.
      METHODS: Two-hundred and fifty-two patients with ischemic stroke were
      retrospectively examined (mean age: 76.7 +/- 10.6 years, 120 males, median delay
      of admission 8 hours). Stroke severity was assessed both on admission and at
      discharge (median stay: 4 days) by the National Institutes of Health Stroke Scale
      (NIHSS). Improvement was defined as a difference between initial and final
      assessment (DeltaNIHSS) >= the median value (2 points). Thus, 127 patients
      improved (mean change: +3.8 points) and 125 did not (mean change: -1.4 points).
      RESULTS: During the first 48 hours of hospitalization, 263 clinical, laboratory,
      instrumental, and therapeutic variables were collected. These were preliminarily
      compared between two subgroups of patients, improved and non-improved, which were
      matched for initial NIHSS score, and 17 possible predictors of improvement were
      found. The subsequent multivariable analysis led to the identification of four
      factors independently associated with improvement (odds ratio, 95% confidence
      interval): total anterior circulation syndrome (TACS) (0.20, 0.10-0.39,
      P<0.0001), aphasia (3.58, 1.89-6.77, P = 0.0001), average systolic blood pressure
      (0.98 per mmHg, 0.96-0.99, P = 0.002), and age (0.97 per year, 0.94-0.99, P =
      0.02). CONCLUSIONS: The ischemic strokes that are not TACS, with aphasia, with
      normal/low blood pressure, or occurring in younger subjects, may have a
      significant tendency to short-term improvement.

PMID- 23561705
TI  - Brown and white fat: from signaling to disease.

PMID- 23561706
TI  - Comparative validation of nomograms predicting clinically insignificant prostate
      cancer.
AB  - OBJECTIVE: To validate and compare the accuracy and performance of nomograms
      predicting insignificant prostate cancer and to analyze their performance in
      patients with different cancer locations. METHODS: Our cohort consisted of 370
      radical prostatectomy patients with Gleason <=6 prostate cancer diagnosed on
      transrectal biopsy with at least 10 cores. We quantified the performance of each
      nomogram with respect to discrimination, calibration, predictive accuracy at
      different cut points, and the clinical net benefit. We also evaluated these
      parameters in subgroups of patients with predominantly anterior-apical (AA) and
      posterior-basal (PB) tumor location. RESULTS: Insignificant prostate cancer was
      present in 141 patients (38%). The Kattan and Steyerberg nomograms outperformed
      other studied models and demonstrated fair discrimination (areas under the
      receiver operating characteristics curve 0.768 and 0.770, respectively), good
      calibration, balanced predictive accuracy, and the highest net benefit. All
      nomograms were less accurate at higher levels of predicted probability. The
      performance of the nomograms was better in patients with PB tumors than in those
      with AA tumors. The loss of correlation with the actual prevalence of
      insignificant prostate cancer at higher levels of predicted probability was not
      seen in the PB subgroup but was particularly noticeable in the AA subgroup.
      CONCLUSION: The Kattan and Steyerberg nomograms demonstrated the best performance
      in predicting the probability of insignificant prostate cancer in a contemporary
      cohort of patients with Gleason <=6 cancer diagnosed on specimens from an
      extended transrectal biopsy. However, all studied nomograms were more accurate in
      identifying significant rather than insignificant disease, particularly for
      tumors located in the apical and anterior prostate.

PMID- 23561707
TI  - Reply: To PMID 23561709.

PMID- 23561708
TI  - SIU Scholar: Dr. Terkaa Atim.

PMID- 23561709
TI  - Varicocelectomy is associated with increases in serum testosterone independent of
      clinical grade.
AB  - OBJECTIVE: To determine whether the varicocele grade is related to the degree of
      improvement in serum testosterone levels after varicocelectomy. MATERIALS AND
      METHODS: We performed a retrospective review of men with a total serum
      testosterone level <400 ng/dL who had undergone microsurgical subinguinal
      varicocelectomy for infertility and/or hypogonadism. All men had clinically
      palpable left varicoceles and preoperative and postoperative total serum
      testosterone levels available. For patients with bilateral varicoceles, the
      greatest grade on either side was used to stratify the patients. The men with an
      isolated, left-side, grade I varicocele were not offered varicocelectomy. The
      changes in the testosterone levels were evaluated, with the results expressed as
      the mean +/- standard error. P <=.05 was considered statistically significant.
      RESULTS: A total of 59 patients had undergone bilateral varicocelectomy and 19
      unilateral varicocelectomy. Overall, an increase in testosterone was seen in 65
      of the 78 men (83%) in the present study. The mean follow-up was 7 months. The
      mean serum testosterone level increased from 308.4 to 417.5 ng/dL, with a mean
      increase of 109.1 +/- 12.8 ng/dL (n = 78). The improvements in the serum
      testosterone levels were seen regardless of the clinical grade. CONCLUSION:
      Microsurgical varicocelectomy resulted in significant increases in the serum
      testosterone level, independent of the varicocele grade.

PMID- 23561710
TI  - Editorial comment.

PMID- 23561711
TI  - Editorial comment.

PMID- 23561712
TI  - Prospective randomized placebo-controlled study to assess the safety and efficacy
      of silodosin in the management of acute urinary retention.
AB  - OBJECTIVE: To determine the safety and efficacy of silodosin in the management of
      acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH).
      METHODS: From January 2011 to May 2012, 60 men over 50 years of age with AUR were
      equally randomized to either silodosin 8 mg once daily or placebo for 3 days
      followed by trial without catheter (TWOC). If the patient re-experienced urinary
      retention or if postvoid residual urine volume was >150 mL, he was re
      catheterized and considered to have a failed TWOC. All patients with a successful
      TWOC on day 3 were started on silodosin regardless of which arm they had belonged
      initially. Uroflowmetry, postvoid residual volume and International Prostate
      Symptom Score (IPSS) were noted at TWOC and after 2 weeks. RESULTS: Baseline
      patient demographics and clinical characteristics were similar in both groups (P
      >.1). The success rate of TWOC was 76.7% in the silodosin group and 36.7% in the
      placebo group (P = .002). On multivariate analysis, patients in silodosin group
      had lesser odds of having a failure (0.13) when compared to those not given
      treatment (P = .008). Among the clinical parameters, a retention volume more than
      800 mL (P = .038) and an IPSS score more than 25 (P = .042) had significantly
      greater odds of failure. There were no adverse effects related to the use of
      silodosin. CONCLUSION: Silodosin significantly increases the chances of
      successful TWOC after AUR.

PMID- 23561713
TI  - Changing stone composition profile of children with nephrolithiasis.
AB  - OBJECTIVE: To determine if this trend toward calcium phosphate stone formation
      exists in children. METHODS: This is a retrospective study of medical records of
      179 children managed at our medical center from 1992-2010 for whom stone analysis
      and other pertinent laboratory data were available. A comparison of patients
      managed from 1992-2000 (P1) and 2001-2010 (P2) was undertaken. Statistical
      analysis included nonparametric tests. RESULTS: There were no significant
      differences in the mean age of the 2 cohorts. During both periods, boys comprised
      a significantly higher proportion during the first decade of life, whereas girls
      comprised a significantly higher proportion during the second decade. A higher
      percentage of patients had calcium oxalate (CaOx) stones in P1 compared to P2
      (60% vs 47%, P = .0019). There was a significant increase in the percentage of
      patients having calcium phosphate stones in P2 compared to P1 (27% vs 18.5%, P =
      .008). Twenty-seven patients had recurrent stones. A comparison of the
      compositions of the first and last stones of patients within this group
      demonstrated an increasing proportion of brushite stones (3.7% vs 11.1%, P =
      .04). Twenty-four hour urine testing results were similar for those with CaOx and
      calcium phosphate stones. CONCLUSION: An increasing proportion of children have
      calcium phosphate calculi. Brushite stones are more prevalent in children with
      recurrent stone events. The impetus of these shifts is not readily apparent.

PMID- 23561714
TI  - Prostate calcification worsen lower urinary tract symptoms in middle-aged men.
AB  - OBJECTIVE: To investigate the correlation between prostatic calcification and
      lower urinary tract symptoms (LUTS) in a sample of middle-aged men receiving
      health checkups. METHODS: Subjects aged 40 years or older who voluntarily
      underwent transrectal prostate ultrasound (TRUS) and fulfilled International
      Prostate Symptoms Score (IPSS) as part of their medical checkup were enrolled in
      this study. The prostatic calcification grading and prostate volume (PV) were
      measured by TRUS. The medical history, demographics, and metabolic markers were
      also evaluated. Logistic regression was used to analyze the correlation between
      prostatic calcification and LUTS. RESULTS: A total of 604 men were enrolled as
      study subjects. The prostatic calcification grading was significantly associated
      with age and PV instead of metabolic markers. Compared to the nonprostatic
      calcification group, the moderate/marked prostatic calcification group had a
      significantly higher age-adjusted IPSS (8.69 vs 6.87, P <.01), quality of life
      (QOL) score (2.57 vs 2.17, P <.01), storage score (3.74 vs 3.06, P = .01),
      voiding score (4.95 vs 3.72, P <.01), and more maximum flow rate <15 mL/sec
      (40.4% vs 24.5%, P <.01). Prostatic calcification grading was positively
      correlated with age-adjusted IPSS, QOL, voiding, and storage scores (all P for
      trend <.05). Further multivariate analysis indicated that moderate/marked
      prostatic calcification was an independent risk factors for moderate to severe
      LUTS (odds ratio [OR] = 1.68, P = .02). CONCLUSION: Prostatic calcification
      worsened IPSS, QOL, storage, voiding symptoms, and maximum urine flow (Qmax) in
      middle-aged men receiving a health checkup. Moderate/marked prostatic
      calcification was an independent risk factor for moderate to severe LUTS.

PMID- 23561715
TI  - [A comparison of AirtraqTM laryngoscope and standard direct laryngoscopy in adult
      patients with immobilized cervical spine].
AB  - INTRODUCTION: Airtraq laryngoscope is a new and single use device for
      endotracheal intubation. Few studies showed the superiority of the Airtraq
      comparing to Macintosh laryngoscope in the setting of difficult intubation. STUDY
      DESIGN: To compare the performance of these two laryngoscopes by simulating a
      situation of reduced mobility of the cervical spine by applying the Manual in
      line stablization (MILS) maneuver. PATIENTS AND METHODS: After obtaining the
      approval of the ethic committee, we realized a prospective single blind
      randomized study. During a 6-month period, 120 consenting patients scheduled for
      ORL or ophthalmologic surgery were included. They all had general anesthesia and
      orotracheal intubation. These patients were randomly and equally divided in two
      groups (n=60), depending on the type of the laryngoscope used (Airtraq or
      Macintosh). Were excluded from the study the patients with history or criteria
      predicting difficult intubation. Each patient was intubated by one of the five
      experimented anesthetists selected for this work. The principle judgment criteria
      were: i) the time taken for the orotracheal intubation and ii) the intubation
      difficulty score (IDS). The secondary judgment criterion was the hemodynamic
      modifications after the endotracheal intubation. RESULTS: Demographic and upper
      airway track variables were comparable between the two groups. There was no case
      of failure of intubation in this serie. Nonetheless, all the patients of the
      Airtaq group were intubated from the first attempt, whereas half of the patients
      of the Macintosh group were intubated after the third attempt. Comparing to the
      Macintosh, the Airtraq reduces the time taken for the orotracheal intubation
      (14+/-1s vs 19+/-3s, P=0.01), the necessity of additional maneuver to facilitate
      the intubation, and the intubation difficulty score (0.7+/-0.3 vs 3.8+/-1,
      P<0.001). Orotracheal intubation using the Airtraq laryngoscope caused less
      hemodynamic stimulation than using the Macintosh. CONCLUSION: Our study showed
      the usefulness of the Airtraq laryngoscope for endotracheal intubation for
      patients presenting conditions of difficult intubation such as reduced mobility
      of the cervical spine.

PMID- 23561716
TI  - [Cost analysis comparing single-use (Ambu(r) aScopeTM) and conventional reusable
      fiberoptic flexible scopes for difficult tracheal intubation].
AB  - OBJECTIVE: Recommendations on difficult tracheal intubation constrain each
      surgical block to have a fiberscope available. Reusable fiberscope presents the
      problem of availability, the risk of non-conventional infections transmission and
      the cost. Single-use fiberscopes are presently available (Ambu(r) aScopeTM). This
      medico-economic study aims to assess the cost of using a reusable fiberscope as
      compared to the single use fiberscope. STUDY DESIGN: Cost minimization analysis.
      MATERIAL: Reusable fiberscope Pentax(r) FB 15P (Pentax France, Argenteuil) and
      single-use fiberscope Ambu(r) aScopeTM (Ambu A/S, Ballerup, Denmark). METHOD:
      Minimization-cost analysis conducted between 2006 and 2012. The amortization cost
      per utilization for two reusable fiberscopes took into account the acquisition
      and maintenance costs, as well as the costs related to disinfection. The cost of
      the single use fiberscope was calculated according to its acquisition cost.
      RESULTS: The total cost of the reusable material was 55,874? over 6years,
      corresponding to a unitary cost of 206? per fiberscopy. During this period, 780
      sterilizations were carried out for a total cost of 32,611?. Acquisition and
      maintenance costs were respectively 18,382? and 4880?. The cost of the single use
      fiberscope is of 200? per fiberscopy. CONCLUSION: This medico-economic evaluation
      shows that the utilization cost of single use and reusable fiberscopes are very
      close. This should be analyzed at the light of some benefits of using single use
      devices for the difficult tracheal intubation.

PMID- 23561717
TI  - Tract-based spatial statistics reveal altered relationship between non-verbal
      reasoning abilities and white matter integrity in autism spectrum disorder.
AB  - Altered brain connectivity accompanies autism spectrum disorders (ASD), but the
      relationship between connectivity and intellectual abilities, which often differs
      within ASD, and between ASD and typically developing (TD) children, is not
      understood. Here, diffusion tensor imaging (DTI) was used to explore the
      relationship between white matter integrity and non-verbal intelligence quotients
      (IQ) in children with ASD and in age- and gender-matched TD children. Tract-based
      spatial statistical analyses (TBSS) of DTI fractional anisotropy (FA) revealed
      altered relationships between white matter and IQ. Different relationships were
      found using within-group analyses, where regions of significant (p < .05,
      corrected) correlations in ASD overlapped minimally with regions of FA-IQ
      correlations in TD subjects. An additional between-groups analysis revealed
      significant correlation differences in widespread cortical and subcortical areas.
      These preliminary findings suggest altered brain connectivity may underlie some
      differences in intellectual abilities of ASD, and should be investigated further
      in larger samples as a function of development.

PMID- 23561718
TI  - Resting brains never rest: computational insights into potential cognitive
      architectures.
AB  - Resting-state networks (RSNs), which have become a main focus in neuroimaging
      research, can be best simulated by large-scale cortical models in which networks
      teeter on the edge of instability. In this state, the functional networks are in
      a low firing stable state while they are continuously pulled towards multiple
      other configurations. Small extrinsic perturbations can shape task-related
      network dynamics, whereas perturbations from intrinsic noise generate excursions
      reflecting the range of available functional networks. This is particularly
      advantageous for the efficiency and speed of network mobilization. Thus, the
      resting state reflects the dynamical capabilities of the brain, which emphasizes
      the vital interplay of time and space. In this article, we propose a new
      theoretical framework for RSNs that can serve as a fertile ground for empirical
      testing.

PMID- 23561719
TI  - Requiem for a CAMP: the life and death of a domestic U.S. drug war institution.
AB  - The life and death of California's Campaign Against Marijuana Planting (CAMP,
      1983-2012) offers a unique analytical window into the time and space of the U.S.
      war on drugs in a global context. This paper draws on CAMP report archives,
      ethnographic interviews, and secondary data sources to locate the significance of
      CAMP, its demise, and enduring legacy for the political economy of domestic
      illicit cannabis production in southern Humboldt County, where it was initially
      focused. I first introduce the economic geography of cannabis production in
      southern Humboldt County and California. In the first part of the paper, using
      theoretical frameworks from Critical Geopolitics and International Relations, I
      examine the geo-politics of CAMP's emergence. In the second part of the paper, I
      examine industrial reterritorialization associated with its geographies of
      enforcement over time. I conclude by discussing the eclipse of its foundational
      logic-and-practice (policing the "Emerald Triangle") by new political and
      economic geographies of power. 

PMID- 23561720
TI  - Diversity and distribution of Blastocystis sp. subtypes in non-human primates.
AB  - Blastocystis SSU-rDNA sequence data from 317 captive and free-living non-human
      primates (NHPs) representing 30 genera of apes, Old and New World (OW and NW)
      monkeys and prosimians were analysed to investigate subtype (ST) and allele
      distribution among hosts. Excluding 20 mixed ST infections, 27% of the sequences
      belonged to ST1, 22% to ST2, 34% to ST3, 1% to ST4, 4% to ST5, 11% to ST8, <1% to
      ST13 and 1% to ST15. The study confirmed cryptic host specificity of ST1 and ST3;
      conversely, considerable overlap in ST2 alleles exists among humans and NHPs.
      Subtype distribution in humans and NHPs differs mainly in that ST4 is rarely
      reported in NHPs while ST5 and ST8 are both unusual in humans. This may be due to
      host specificity and/or the apparent geographically restricted range of some
      subtypes. While the distribution of ST1, ST2 and ST3 was independent of NHP group
      or geographical association, ST5 was seen only in apes and OW monkeys and ST8
      primarily in arboreal NHPs and only in species native to Asia or South America.

PMID- 23561721
TI  - Management of gunshot wounds to the hand: a literature review.
AB  - Hand trauma resulting from firearms is becoming more common in civilian life. In
      the past, as in wartime, infection was a main source of concern following firearm
      related hand injuries, whereas in current civilian life with modern medical care,
      infection rates are actually low for such injuries. As infection is now of lesser
      concern, the focus should shift to improve functional outcomes. This review
      summarizes available literature regarding the management of gunshot wounds to the
      hand, with particular focus on functional outcomes. In conducting this review, we
      found that there is not comprehensive information regarding management of gunshot
      wounds to the hand, and literature discussing functional recovery of the hand is
      limited. Given the current evidence related to management of gunshot wounds to
      the hand, we believe that early debridement, antibiotic treatment,
      reconstruction, and rehabilitation offer patients the best chance for full
      functional recovery. 

PMID- 23561722
TI  - The most cited articles in hand surgery over the past 20-plus years: a modern-day
      reading list.
AB  - PURPOSE: To create a current reading list of the hand surgery articles most
      commonly cited in the last 20-plus years. METHODS: Using the Web of Science
      Citation Index Search, we searched "hand" and "wrist" in the orthopedic, surgery,
      and sport sciences research areas. We then reviewed the articles and chose the 50
      most commonly cited articles related to hand surgery. Articles were categorized
      as clinical or basic science. Clinical articles were subcategorized as either
      therapeutic, prognostic, diagnostic, or economic/decision analysis and assigned a
      level of evidence rating. We calculated the number of citations per year
      (citation density). RESULTS: The total number of citations for the top 50
      articles ranged from 92 to 317. Citation density ranged from 4 to 24 (average,
      9.7). Of the 50 articles, 39 were clinical (78%), whereas the remainder were
      basic science. Clinical articles were most commonly therapeutic (25 of 39; 64%),
      followed by diagnostic (11 of 39; 28%) and prognostic (3 of 39; 8%). There were
      no economic/decision analysis-type articles. The most common level of evidence
      was level IV, which made up 38% of the list (19 of 50 articles). The second most
      common was level I, which represented 20% of the list (10 of 50 articles). A
      total of 70% of the articles (35 of 50) were published between 1990 and 1999, and
      the remainder of the articles were published after 1999. Fifty percent of the
      articles appeared in the Journal of Hand Surgery, American volume. CONCLUSIONS:
      Many of the articles found on our list have shaped the way we practice hand
      surgery today. We hope that this report and the articles it names can help
      residents and fellows study current hand surgery and its evolution over the past
      20 years. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and decision analyses IV.

PMID- 23561723
TI  - Long-term results of vascularized bone graft for stage III Kienbock disease.
AB  - PURPOSE: Vascularized bone grafting (VBG) is one of the therapeutic approaches
      for treating advanced Kienbock disease; however, few reports on long-term
      outcomes are available for this technique. The purpose of this study is to
      evaluate long-term results by following up patients with stage III Kienbock
      disease for more than 10 years after VBG. METHODS: The study included 18 patients
      with advanced Kienbock disease (Lichtman stage IIIA, n = 10; stage IIIB, n = 8)
      who received VBG between 1996 and 2001 and were followed up for at least 10
      years. Eleven patients received transplantation from the metacarpal base and 7
      patients from the distal radius. Radial shortening and capitate shortening were
      performed in 5 and 2 stage IIIB patients, respectively. RESULTS: The mean follow
      up period was 12 years, 3 months. Based on the Mayo Modified Wrist Score,
      clinical results were excellent in 8 patients, good in 7 patients, and fair in 3
      patients. The Stahl index and carpal height ratio were not improved in stage IIIA
      patients who received bone graft alone, whereas significant improvement was
      observed in stage IIIB patients who received shortening, as well. CONCLUSIONS:
      Vascularized bone grafting for stage III Kienbock disease demonstrated favorable
      long-term results and is recommended as a surgical treatment. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Therapeutic III.

PMID- 23561724
TI  - Management of the hand in systemic sclerosis.

PMID- 23561725
TI  - Kinematic changes in elbow osteoarthritis: in vivo and 3-dimensional analysis
      using computed tomographic data.
AB  - PURPOSE: To investigate in vivo 3-dimensional kinematics in elbow osteoarthritis.
      We hypothesized that normal kinematics is preserved in an osteoarthritic elbow
      with a normal radiocapitellar joint (OAN). Conversely, we hypothesized that an
      osteoarthritic elbow with radiocapitellar degenerative changes (OAD) would show
      an abnormal kinematics pattern. Furthermore, the differences in osteophyte
      formation between groups may affect elbow kinematics. METHODS: We examined 7
      normal elbows, 7 OAN elbows, and 9 OAD elbows. We investigated 3-dimensional
      kinematics using computed tomography registration techniques. The osteophyte
      location was determined using 3-dimensional bone models generated from computed
      tomography data. RESULTS: The kinematics is different in OAN and OAD elbows. In
      the OAN group, the ulna changed by 11 degrees  from a valgus to a varus position
      during elbow flexion and demonstrated a 4 degrees  change in the axis of elbow
      motion, similar to that in normal elbows. Osteophytes formed medially on the
      olecranon fossa. In the OAD group, the ulna changed by 4 degrees  varus during
      flexion from the 90 degrees  position, but only by 2 degrees  valgus during elbow
      extension from 90 degrees . The change in the axis of elbow motion was 9 degrees
      . Additional osteophytes formed on the anteromedial and lateral trochlea, lateral
      olecranon fossa, and medial olecranon of the ulnotrochlear joint, and on the
      radiocapitellar joint. CONCLUSIONS: Normal kinematics was preserved in the OAN
      group. The OAD group demonstrated marked changes in the direction of elbow motion
      in the extension range, and the valgus motion pattern during extension was
      decreased. CLINICAL RELEVANCE: The results of the current study provide a good
      starting point for further research into the nature of arthritic progression in
      the elbow joint and the role of debridement arthroplasty.

PMID- 23561727
TI  - Management of radial nerve palsy associated with humerus fracture.

PMID- 23561728
TI  - The effects of adjuvant fibrin sealant on the surgical repair of segmental nerve
      defects in an animal model.
AB  - PURPOSE: Nerve repair after a segmental defect injury remains a challenge for
      surgeons. Fibrin glue can be used to expedite surgical procedures and maintain
      proper nerve spatial orientation to potentially optimize recovery, yet surgeons
      hesitate to use it owing to concerns about fibrin's inhibiting regeneration and
      increasing scar formation. The purpose of these experiments was to evaluate
      whether fibrin glue impedes nerve regeneration. METHODS: A critical-size defect
      of 10 mm was created in 32 Sprague-Dawley rats with 4 different forms of repair:
      a collagen type-I conduit (n = 8), a collagen type-I conduit filled with fibrin
      glue (n = 8), an autologous nerve graft (n=8), and an autologous nerve graft with
      fibrin glue (n = 8). Behavioral tests, including sciatic functional indices, were
      used to evaluate functional recovery. Neurophysiology, immunohistochemistry, and
      nerve morphometry were used to critically analyze nerve regeneration. RESULTS:
      Multiple outcome parameters for nerve regeneration, remyelination, behavior, and
      electrophysiology were used to determine that the addition of fibrin did not
      influence recovery for the autograft groups. Similarly, within the conduit group,
      behavioral tests showed comparable functional recovery and indistinguishable
      results in compound motor action potential and nerve morphometry.
      Immunohistochemistry revealed identical degrees of Wallerian degeneration and
      scarring between conduit groups. CONCLUSIONS: The addition of fibrin to either
      the conduit or the autograft group did not result in any meaningful differences
      in recovery. Our data demonstrate that fibrin glue does not impede nerve
      regeneration or functional recovery after surgical repair of a segmental nerve
      defect in a rat model. CLINICAL RELEVANCE: The clinical use of fibrin glue as an
      adjunct with peripheral nerve repair may be considered safe because it does not
      impair nerve regeneration with critical size defects in an animal model.

PMID- 23561729
TI  - Clinical outcomes of arthrodesis and arthroplasty for the treatment of
      posttraumatic wrist arthritis.
AB  - PURPOSE: To compare clinical outcomes of wrist arthrodesis and total wrist
      arthroplasty in the treatment of pancarpal posttraumatic arthritis. We
      hypothesized that arthroplasty would demonstrate better clinical outcomes than
      wrist arthrodesis. METHODS: We performed a retrospective review of 22 patients
      treated (15 arthrodeses and 7 arthroplasties) for pancarpal posttraumatic
      arthritis. We measured clinical outcomes with the visual analog pain scale;
      Disabilities of the Arm, Shoulder, and Hand questionnaire; the Patient-Rated
      Wrist Evaluation; and a study-specific questionnaire. Postoperative complications
      were recorded from chart review. RESULTS: Mean follow-up was 68 months for
      arthrodesis and 56 months for arthroplasty. The mean visual analog scale pain
      score was 2 for each group. The mean Disabilities of the Arm, Shoulder, and Hand
      score was 38 for the arthrodesis group and 29 for the arthroplasty group. The
      mean Patient-Rated Wrist Evaluation was 73 for the arthrodesis group and 31 for
      the arthroplasty group. The results from the study-specific questionnaire
      revealed that the majority of patients in both groups were satisfied.
      Complication rates were similar in both groups. CONCLUSIONS: Total wrist
      arthroplasty as an alternative to arthrodesis for the treatment of pancarpal
      posttraumatic arthritis may offer improved functional outcomes. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 23561730
TI  - Rupture of the profunda femoris artery in a patient with alcoholic liver disease:
      a case report.
AB  - INTRODUCTION: Profunda femoris artery aneurysms are rare and often present with
      rupture. However, to the best of our knowledge, rupture of a non-aneurismal
      profunda femoris artery has never been reported before. CASE PRESENTATION: We
      report the case of a 31-year-old Caucasian man with alcoholic liver disease who
      presented with rupture of the profunda femoris artery following blunt trauma
      which was treated by endovascular embolization. CONCLUSION: Coagulopathy
      secondary to alcoholic liver disease is a major contributory factor and a high
      index of suspicion of vascular injury must be attached to such patients following
      blunt trauma. Although there have no previous documented cases, treatment by
      endovascular embolization appears to be effective and safe.

PMID- 23561731
TI  - [Hormones metabolism and cancer, new horizons].

PMID- 23561726
TI  - Variation in recommendation for surgical treatment for compressive neuropathy.
AB  - PURPOSE: It is our impression that there is substantial, unexplained variation in
      hand surgeon recommendations for treatment of peripheral mononeuropathy. We
      tested the null hypothesis that specific patient and provider factors do not
      influence recommendations for surgery. METHODS: Using a web-based survey, hand
      surgeons recommended surgical or nonsurgical treatment for patients in 2
      different scenarios. Six elements of the first scenario (symptoms, circumstances,
      mindset, diagnosis, objective testing, and expectations) had 2 possibilities that
      were each independently and randomly assigned to each rater. For the second
      scenario, 2 different scenarios were randomly assigned to each rater.
      Multivariable logistic regression sought factors associated with a recommendation
      for surgery. RESULTS: A total of 186 surgeons of the Science of Variation Group
      completed a survey regarding recommendation of surgery for 2 different patients
      based on clinical scenarios. Recommendations for surgery did not vary
      significantly according to provider characteristics. For the various elements in
      scenario 1, recommendation for surgery was more likely for patients who were self
      employed and continued to work and who had objective electrodiagnostic
      abnormalities. For the 2 vignettes used in scenario 2, a recommendation for
      surgery was associated with abnormal electrophysiology. CONCLUSIONS: The findings
      of this study suggest that-at least in a survey setting-surgeons prefer to offer
      peripheral nerve decompression to patients with abnormal electrophysiology,
      particularly those with effective coping strategies. CLINICAL RELEVANCE: The role
      of objective verification of pathophysiology is debated, but it is an influential
      factor in recommendations for hand surgery.

PMID- 23561732
TI  - Systematic optimisation and evaluation of on-line, off-line and stop-flow
      comprehensive hydrophilic interaction chromatography*reversed phase liquid
      chromatographic analysis of procyanidins, part I: theoretical considerations.
AB  - Comprehensive two-dimensional liquid chromatography (LC*LC) provides
      significantly improved separation for complex real-life samples. LC*LC can be
      performed in one of three different ways, using on-line, off-line, or stop-flow
      configurations. We have previously shown how off-line comprehensive hydrophilic
      interaction chromatography (HILIC)*reversed-phase liquid chromatography (RP-LC)
      provides a powerful separation system for procyanidins (PCs), one of the most
      complex fractions of natural phenolics. In the current contribution, a systematic
      approach for the optimisation and evaluation of each of the LC*LC methodologies
      is presented using HILIC*RP-LC analysis of PCs as application. Optimisation was
      performed using the peak capacities of individual one-dimensional separations
      measured for different gradient times and flow rates and their combination in
      each of the three LC*LC modes by taking into account the effects of first
      dimension under-sampling, the degree of orthogonality between the two dimensions
      and additional band broadening associated with stop-flow analysis. The
      performance of all three methods is compared in terms of practical peak
      capacities, analysis times and peak production rates. One-dimensional LC provided
      the best performance for separations requiring relatively low peak capacities,
      whereas the on-line LC*LC system was advantageous for required practical peak
      capacities up to ~600. For higher resolution, the off-line or stop-flow systems
      should be used. Especially noteworthy is the fact that, due to slow diffusion of
      PCs, the contribution of stop-flow to first dimension band broadening was
      negligible for stop-flow times of up to 15min. In a separate contribution, the
      experimental verification of the findings of this study will be reported.

PMID- 23561733
TI  - Design and implementation of injector/distributor structures for microfabricated
      non-porous pillar columns for capillary electrochromatography.
AB  - A previously proposed foil definition is applied in the design of
      injector/distributor structures for solid microfabricated column structures for
      capillary electrochromatography. In addition to a typical bifurcated distributor,
      an optimized design alternative with two different configurations is
      experimentally evaluated. Optimized designs yielded a flat profile for the
      injected sample with a maximum of 3% variation from the mean width, while it went
      up to 18% for the typical bifurcated distributor. The implemented electrokinetic
      injection approach enabled controlling the volume of the injected sample
      accurately without sacrificing the compactness of the device design. The width of
      the injected sample was directly proportional to the injection time, namely 165
      and 218 MUm base widths were obtained for 0.6 and 0.8s of feeding, respectively.
      Reducing the external porosity of the distributor by 85% compared to the typical
      design, optimized distributors caused a decrease in the mean flow velocity of up
      to 70%. However, having a flat initial plug shape enabled the separation of a
      mixture of Coumarin 440, 460, 480 and 540 at 1 mm downstream of the injection
      point in 80s, while it was even not possible to detect the C440 signal for a
      typical bifurcated design.

PMID- 23561735
TI  - Compliance with the minimum dataset of the British Orthodontic Society/British
      Association of Oral and Maxillofacial Surgeons for record keeping for
      orthognathic patients: retrospective comparative multicentre audit.
AB  - Accurate and timely collection of clinical records is of utmost importance in
      planning, evaluating, and auditing orthognathic operations. The minimum dataset
      guidelines of the British Orthodontic Society (BOS) and the British Association
      of Oral and Maxillofacial Surgeons (BAOMS) were published in an attempt to
      standardise the collection of clinical records of patients having orthognathic
      operations. This multicentre retrospective audit aimed to assess and compare
      compliance with the guidelines in 3 maxillofacial units over a 1-year period. A
      total of 105 cases were reviewed. Compliance varied. Documentation of altered
      sensation was consistently poor and too many unnecessary radiographs were taken.
      There may be a need to circulate the guidelines again to increase awareness and
      reduce variability between centres. 

PMID- 23561734
TI  - Salamander Hox clusters contain repetitive DNA and expanded non-coding regions: a
      typical Hox structure for non-mammalian tetrapod vertebrates?
AB  - Hox genes encode transcription factors that regulate embryonic and post-embryonic
      developmental processes. The expression of Hox genes is regulated in part by the
      tight, spatial arrangement of conserved coding and non-coding sequences. The
      potential for evolutionary changes in Hox cluster structure is thought to be low
      among vertebrates; however, recent studies of a few non-mammalian taxa suggest
      greater variation than originally thought. Using next generation sequencing of
      large genomic fragments (>100 kb) from the red spotted newt (Notophthalamus
      viridescens), we found that the arrangement of Hox cluster genes was conserved
      relative to orthologous regions from other vertebrates, but the length of introns
      and intergenic regions varied. In particular, the distance between hoxd13 and
      hoxd11 is longer in newt than orthologous regions from vertebrate species with
      expanded Hox clusters and is predicted to exceed the length of the entire HoxD
      clusters (hoxd13-hoxd4) of humans, mice, and frogs. Many repetitive DNA sequences
      were identified for newt Hox clusters, including an enrichment of DNA transposon
      like sequences relative to non-coding genomic fragments. Our results suggest that
      Hox cluster expansion and transposon accumulation are common features of non
      mammalian tetrapod vertebrates.

PMID- 23561736
TI  - Unrestricted somatic stem cells as vehicle for nerve growth factor gene transfer.
AB  - OBJECTIVE: Nerve growth factor (NGF), a member of the neurotrophic factor family,
      plays a critical role in the maintenance and regeneration of different types of
      neurons. To overcome drastic challenges in the peripheral delivery of NGF,
      transplantation of NGF secreting stem cells to the target site of an injury may
      be an effective procedure. Unrestricted somatic stem cells (USSCs), a subtype of
      umbilical cord blood (UCB) stem cells, have shown promise for gene therapy
      purposes, and proper results have been observed from transplantation experiments
      in neurodegenerative disorders. Based on the considerable potential of USSCs for
      gene delivery applications, the goal of the current study was to establish a
      betaNGF gene containing USSCs, which is able to secrete functional recombinant
      betaNGF protein. METHODS: Unrestricted somatic stem cells were isolated from UCB
      and were cultured in a DMEM medium. The betaNGF gene was cloned in the EFalpha
      promoting lentiviral vector, and virus production was performed as a third
      generation lentivirus packaging system. Enzyme-linked immunosorbent assay, real
      time PCR, co-culture, MTT, and immunocytochemistry assays were performed to
      evaluate the genetically engineered USSCs. RESULTS: Overexpression of betaNGF
      gene in human USSCs created a USSC line that is able to secrete high amounts of
      functional betaNGF protein. betaNGF-secreting USSCs showed a high rate of
      viability along with acceptable immunological and morphological properties for
      transplantation into the nervous system. DISCUSSION: Long-term expression of
      functional betaNGF, high viability of betaNGF producing USSCs, and expression of
      primary neuronal markers suggest that USSCs may be useful to deliver betaNGF into
      targeted sites of the nervous system in neurodegenerative disorders.

PMID- 23561737
TI  - [Enigmatic lymphatic diseases involving the lung].
AB  - Lymphedema associated with other developmental malformations (Milroy syndrome,
      Hennekam syndrome, Noonan syndrome, Gorham-Stout syndrome, yellow nail syndrome)
      are unfrequent disease, but explorations led to the identification of genetic
      mutations that have then been validated in mouse models. However, lymphatic
      vessels complexity and its proximity with the venous system suggest the need for
      further researches, especially in the comprehension of pulmonary symptoms. 

PMID- 23561738
TI  - Cancer treatment and antimicrobial resistance.

PMID- 23561739
TI  - Cancer control in Africa: which priorities?

PMID- 23561740
TI  - Challenges for paediatric oncology in Africa.

PMID- 23561741
TI  - Cancer in Ethiopia.
AB  - Ethiopia has a population of more than 84 million people and is expected to
      become the ninth most populous country in the world by 2050. The growing
      population coupled with lifestyle changes will mean an increasing burden of
      cancer. However, oncology services are wholly inadequate--no cancer registry
      exists, and only one cancer centre, with a handful of doctors and nurses,
      struggles to serve the entire country.

PMID- 23561742
TI  - Building a pathology laboratory in Malawi.
AB  - Until recently, the Malawian capital of Lilongwe was without diagnostic pathology
      services, which left many patients with cancer facing serious diagnostic delays.
      Through collaboration with the University of North Carolina and other partners, a
      pathology laboratory was successfully established at Kamuzu Central Hospital in
      July, 2011, providing an essential foundation for cancer diagnosis and research
      in the country's largest city.

PMID- 23561743
TI  - At the crossroads of targeted treatment and resistance in melanoma.

PMID- 23561744
TI  - Access to cancer medicines in India.

PMID- 23561745
TI  - Challenges and opportunities in cancer control in Africa: a perspective from the
      African Organisation for Research and Training in Cancer.
AB  - Sub-Saharan Africa has a disproportionate burden of disease and faces a major
      public-health challenge from non-communicable diseases. Although infectious
      diseases continue to afflict Africa, the proportion of the overall disease burden
      in sub-Saharan Africa attributable to cancer is rising. The region is predicted
      to have a greater than 85% increase in cancer burden by 2030. Approaches to
      minimise the burden of cancer in sub-Saharan Africa in the past few years have
      had little success because of low awareness of the cancer burden and a poor
      understanding of the potential for cancer prevention. Success will not be easy,
      and will need partnerships and bridges to be built across countries, economies,
      and professions. A strategic approach to cancer control in sub-Saharan Africa is
      needed to build on what works there and what is unique to the region. It should
      ideally be situated within strong, robust, and sustainable health-care systems
      that offer quality health care to all people, irrespective of their social or
      economic standing. However, to achieve this will need new leadership, critical
      thinking, investment, and understanding. We discuss the present situation in sub
      Saharan Africa and propose ideas to advance cancer control in the region,
      including the areas of cancer awareness, advocacy, research, workforce, care,
      training, and funding.

PMID- 23561746
TI  - Improvement of pathology in sub-Saharan Africa.
AB  - In the coming decades, cancer will be a major clinical and public health issue in
      sub-Saharan Africa. However, clinical and public health infrastructure and
      services in many countries are not positioned to deal with the growing cancer
      burden. Pathology is a core service required to serve many needs related to
      cancer in sub-Saharan Africa. Cancer diagnosis, treatment, and research all
      depend on adequate pathology. Pathology is also necessary for cancer
      registration, which is needed to accurately estimate cancer incidence and
      mortality. Cancer registry data directly guide policy-makers' decisions for
      cancer control and the allocation of clinical and public health services. Despite
      the centrality of pathology in many components of cancer care and control,
      countries in sub-Saharan Africa have at best a tenth of the pathology coverage of
      that in high-income countries. Equipment, processes, and services are lacking,
      and there is a need for quality assurance for the definition and implementation
      of high-quality, accurate diagnosis. Training and advocacy for pathology are also
      needed. We propose approaches to improve the status of pathology in sub-Saharan
      Africa to address the needs of patients with cancer and other diseases.

PMID- 23561747
TI  - Treatment of cancer in sub-Saharan Africa.
AB  - Cancer is rapidly becoming a public health crisis in low-income and middle-income
      countries. In sub-Saharan Africa, patients often present with advanced disease.
      Little health-care infrastructure exists, and few personnel are available for the
      care of patients. Surgeons are often central to cancer care in the region, since
      they can be the only physician a patient sees for diagnosis, treatment (including
      chemotherapy), and palliative care. Poor access to surgical care is a major
      impediment to cancer care in sub-Saharan Africa. Additional obstacles include the
      cost of oncological care, poor infrastructure, and the scarcity of medical
      oncologists, pathologists, radiation oncologists, and other health-care workers
      who are needed for cancer care. We describe treatment options for patients with
      cancer in sub-Saharan Africa, with a focus on the role of surgery in relation to
      medical and radiation oncology, and argue that surgery must be included in public
      health efforts to improve cancer care in the region.

PMID- 23561748
TI  - Status of radiotherapy resources in Africa: an International Atomic Energy Agency
      analysis.
AB  - Radiation therapy is an important component of cancer control programmes. The
      scarcity of radiation oncology resources in Africa is becoming more severe as
      cancer incidence increases in the continent. We did a longitudinal assessment of
      the status of radiation oncology resources in Africa to measure the extent of the
      problem and the effects of programmes designed to enhance radiation services in
      the continent. Radiation oncology departments in Africa were surveyed through the
      Directory of Radiotherapy Centres, and this information was supplemented by that
      available from International Atomic Energy Agency Regional African and
      Interregional project reports for 2010. Of 52 African countries included, only 23
      are known to have teletherapy. These facilities are concentrated in the southern
      and northern states of the continent. Brachytherapy resources (high-dose rate or
      low-dose rate) were only available in 20 of the 52 African countries. Although
      progress has been made in the establishment of radiation oncology services in
      some countries, a large need still exists for basic radiation services, and much
      resource mobilisation is needed for services to keep pace with the burgeoning
      populations of many countries.

PMID- 23561749
TI  - Improving access to analgesic drugs for patients with cancer in sub-Saharan
      Africa.
AB  - WHO expects the burden of cancer in sub-Saharan Africa to grow rapidly in coming
      years and for incidence to exceed 1 million per year by 2030. As a result of late
      presentation to health facilities and little access to diagnostic technology,
      roughly 80% of cases are in terminal stages at the time of diagnosis, and a large
      proportion of patients have moderate to severe pain that needs treatment with
      opioid analgesics. However, consumption of opioid analgesics in the region is low
      and data suggest that at least 88% of cancer deaths with moderate to severe pain
      are untreated. Access to essential drugs for pain relief is limited by legal and
      regulatory restrictions, cultural misperceptions about pain, inadequate training
      of health-care providers, procurement difficulties, weak health systems, and
      concerns about diversion, addiction, and misuse. However, recent initiatives
      characterised by cooperation between national governments and local and
      international non-governmental organisations are improving access to pain relief.
      Efforts underway in Uganda, Kenya, and Nigeria provide examples of challenges
      faced and innovative approaches adopted and form the basis of a proposed
      framework to improve access to pain relief for patients with cancer across the
      region.

PMID- 23561750
TI  - Research into palliative care in sub-Saharan Africa.
AB  - Roughly half a million people die of cancer in sub-Saharan Africa every year.
      Despite rapid expansion of palliative care for cancer, coverage remains woefully
      inadequate. The WHO public health strategy for palliative care aims to increase
      access to palliative care services through its integration into health-care
      systems. We present the available evidence for the four WHO strategy pillars of
      policy, education, drug availability, and implementation, and propose a fifth
      pillar of research activity to stimulate improvement of care. Increased attention
      to the generation of research evidence is essential to achieve quality and
      coverage of appropriate palliative care for patients with advanced cancer in sub
      Saharan Africa. The use of locally validated, patient-reported outcome measures
      is an important advance in the measurement and improvement of care and patient
      wellbeing. Palliative care for patients with cancer in Africa currently receives
      far less research attention than does palliative care for patients with HIV/AIDS,
      but in view of projected increasing cancer incidence in the region, generation of
      local evidence to inform and allow assessment of palliative care for patients
      with cancer is urgently needed.

PMID- 23561751
TI  - Developing cancer control plans in Africa: examples from five countries.
AB  - The creation and implementation of national cancer control plans is becoming
      increasingly necessary for countries in Africa, with the number of new cancer
      cases per year in the continent expected to reach up to 1.5 million by 2020.
      Examples from South Africa, Egypt, Nigeria, Ghana, and Rwanda describe the state
      of national cancer control plans and their implementation. Whereas in Rwanda the
      emphasis is on development of basic facilities needed for cancer care, in those
      countries with more developed economies, such as South Africa and Nigeria, the
      political will to fund national cancer control plans is limited, even though the
      plans exist and are otherwise well conceived. Improved awareness of the
      increasing burden of cancer and increased advocacy are needed to put pressure on
      governments to develop, fund, and implement national cancer control plans across
      the continent.

PMID- 23561752
TI  - Place and food insecurity: a critical review and synthesis of the literature.
AB  - OBJECTIVE: In some high-income countries, a sizeable proportion of households are
      estimated to be food insecure. It is well known that food insecurity varies
      between countries and is strongly tied to household income level. The local
      environment may be another level of influence, which has been relatively
      understudied. The present review sought to synthesize and critically appraise the
      existing literature examining local environmental characteristics in relation to
      individual/household-level food insecurity in the general population. DESIGN: A
      systematic search strategy was used to search MEDLINE, MEDLINE In-process and
      Other Non-indexed, EMBASE, PsychINFO, Social Services Abstracts and Sociological
      Abstracts databases for studies examining local place characteristic(s) in
      relation to self-reported food insecurity. SETTING: Studies could be experimental
      or observational, but had to be published in a peer-reviewed journal in French or
      English, and involve individuals from developed countries. 'Place' was defined
      locally, as ranging from the street to the county level. SUBJECTS: The target
      population for the review included non-institutionalized individuals in the
      general population. RESULTS: After obtaining full-text articles, eighteen primary
      studies met the eligibility criteria. Most studies were conducted in the USA and
      all but one was cross-sectional. Seven of the eleven studies that examined
      location of residence found that rural living was inversely associated with food
      insecurity. Mixed results were seen for other place measures such as social
      capital and distance to food stores. CONCLUSIONS: Studies were heterogeneous and
      had various limitations that preclude definitive conclusions from being drawn.
      Recommendations for future research are provided.

PMID- 23561754
TI  - Access to general practice in a time of austerity.

PMID- 23561755
TI  - Use of email for consulting with patients in general practice.

PMID- 23561756
TI  - Health literacy and the 'inverse information law'.

PMID- 23561757
TI  - Diagnostic uncertainty: dichotomies are not the answer.

PMID- 23561758
TI  - Outside the Box: proactive care: the patient's right to choose.

PMID- 23561759
TI  - Primary health care: what role for occupational health?

PMID- 23561760
TI  - Outside the Box: Proactive care: the patient's right to choose.

PMID- 23561761
TI  - Symptoms and risk factors to identify people with suspected cancer in primary
      care.

PMID- 23561762
TI  - Symptoms and risk factors to identify people with suspected cancer in primary
      care.

PMID- 23561763
TI  - Problems with hypertension guidelines.

PMID- 23561764
TI  - The use of written material in consultations.

PMID- 23561766
TI  - Asking the shisha question.

PMID- 23561768
TI  - Formative assessments in medical education: are excessive, and erode the learning
      and teaching experience.

PMID- 23561767
TI  - Enhancing consultations with interpreters: learning more about how.

PMID- 23561769
TI  - An A-Z of medical philosophy.

PMID- 23561770
TI  - Option grids: an idea whose time has come?

PMID- 23561771
TI  - Patients with long-term conditions, their carers, and advocates.

PMID- 23561773
TI  - First do no harm: education deals with the application of general principles in
      uncertain situations.

PMID- 23561780
TI  - Lessons from Mackenzie that still resonate.

PMID- 23561781
TI  - An unexpected cause of digital gangrene: HIV associated peripheral arterial
      thrombosis.

PMID- 23561782
TI  - Tips for GP trainees working in rheumatology.

PMID- 23561783
TI  - Accessing primary care: a simulated patient study.
AB  - BACKGROUND: Simulated patient, or so-called 'mystery-shopper', studies are a
      controversial, but potentially useful, approach to take when conducting health
      services research. AIM: To investigate the construct validity of survey questions
      relating to access to primary care included in the English GP Patient Survey.
      DESIGN AND SETTING: Observational study in 41 general practices in rural, urban,
      and inner-city settings in the UK. METHOD: Between May 2010 and March 2011,
      researchers telephoned practices at monthly intervals, simulating patients
      requesting routine, but prompt, appointments. Seven measures of access and
      appointment availability, measured from the mystery-shopper contacts, were
      related to seven measures of practice performance from the GP Patient Survey.
      RESULTS: Practices with lower access scores in the GP Patient Survey had poorer
      access and appointment availability for five out of seven items measured
      directly, when compared with practices that had higher scores. Scores on items
      from the national survey that related to appointment availability were
      significantly associated with direct measures of appointment availability.
      Patient-satisfaction levels and the likelihood that patients would recommend
      their practice were related to the availability of appointments. Patients'
      reports of ease of telephone access in the national survey were unrelated to
      three out of four measures of practice call handling, but were related to the
      time taken to resolve an appointment request, suggesting responders' possible
      confusion in answering this question. CONCLUSION: Items relating to the
      accessibility of care in a the English GP patient survey have construct validity.
      Patients' satisfaction with their practice is not related to practice call
      handling, but is related to appointment availability.

PMID- 23561785
TI  - Sharing control of appointment length with patients in general practice: a
      qualitative study.
AB  - BACKGROUND: There is little published research into the impact, on both doctor
      and patient, of handing over responsibility for choosing appointment length to
      the patient. AIM: To investigate what impact giving patients control of their
      appointment length has on the patient and doctor experience. DESIGN AND SETTING:
      A qualitative study in a single medical practice in Inverness, Scotland. METHOD:
      Eligible patients making a 'routine' appointment were given a choice of
      appointment length (5, 10, 15, or 20 minutes). After the consultation, patients
      were invited to take part in a focused interview. Doctors were asked to keep an
      audio diary and their experience was explored further in a facilitated focus
      group. Data were analysed using a thematic analysis approach. RESULTS: Key themes
      that emerged for patients included the impact of the shift in power and the
      impact of introducing the issue of time. For doctors, important themes that
      emerged were impacts on the provider, on the doctor-patient relationship, and on
      the consultation. CONCLUSION: Giving patients greater responsibility for choosing
      appointment length may improve the experience for both doctors and patients.

PMID- 23561784
TI  - Slaying the dragon myth: an ethnographic study of receptionists in UK general
      practice.
AB  - BACKGROUND: General practice receptionists fulfil an essential role in UK primary
      care, shaping patient access to health professionals. They are often portrayed as
      powerful 'gatekeepers'. Existing literature and management initiatives advocate
      more training to improve their performance and, consequently, the patient
      experience. AIM: To explore the complexity of the role of general practice
      receptionists by considering the wider practice context in which they work.
      DESIGN AND SETTING: Ethnographic observation in seven urban general practices in
      the north-west of England. METHOD: Seven researchers conducted 200 hours of
      ethnographic observation, predominantly in the reception areas of each practice.
      Forty-five receptionists were involved in the study and were asked about their
      work as they carried out their activities. Observational notes were taken.
      Analysis involved ascribing codes to incidents considered relevant to the role
      and organising these into related clusters. RESULTS: Receptionists were faced
      with the difficult task of prioritising patients, despite having little time,
      information, and training. They felt responsible for protecting those patients
      who were most vulnerable, however this was sometimes made difficult by protocols
      set by the GPs and by patients trying to 'play' the system. CONCLUSION: Framing
      the receptionist-patient encounter as one between the 'powerful' and the
      'vulnerable' gets in the way of fully understanding the complex tasks
      receptionists perform and the contradictions that are inherent in their role.
      Calls for more training, without reflective attention to practice dynamics, risk
      failing to address systemic problems, portraying them instead as individual
      failings.

PMID- 23561786
TI  - Operationalising unscheduled care policy: a qualitative study of healthcare
      professionals' perspectives.
AB  - BACKGROUND: UK health policy aims to reduce the use of unscheduled care, by
      increasing proactive and preventative management of patients with long-term
      conditions in primary care. AIM: The study explored healthcare professionals'
      understanding of why patients with long-term conditions use unscheduled care, and
      the healthcare professionals' understanding of their role in relation to reducing
      the use of unscheduled care. DESIGN AND SETTING: Qualitative study interviewing
      different types of healthcare professionals providing primary care or unscheduled
      care services in northwest England. METHOD: Semi-structured interviews were
      conducted with 29 healthcare professionals (six GPs; five out-of-hours GPs; four
      emergency department doctors; two practice nurses; three specialist nurses; two
      district nurses; seven active case managers). Data were analysed using framework
      analysis. RESULTS: Healthcare professionals viewed the use of unscheduled care as
      a necessary component of care for patients with long-term conditions. Those whose
      roles involved working to targets to reduce the use of unscheduled care described
      a tension between this and delivering optimum patient care. Three approaches to
      reducing unscheduled care were described: optimising the system; negotiating the
      system; and optimising the patient. CONCLUSION: Current policy to reduce the use
      of unscheduled care does not take account of the perceptions of the healthcare
      professionals who are expected to implement them. Lipsky's theory of street-level
      bureaucrats provides a framework to understand how healthcare professionals
      respond to imposed policies. Healthcare professionals did not see the use of
      unscheduled care as a problem and there was limited commitment to the policy
      targets. Therefore, policy should aim for whole-system change rather than
      reliance on individual healthcare professionals to make changes in their
      practice.

PMID- 23561787
TI  - Challenges to the credibility of patient feedback in primary healthcare settings:
      a qualitative study.
AB  - BACKGROUND: The UK government has encouraged NHS services to obtain patient
      feedback to support the further development of patient-centred care. In 2009, the
      English GP Patient Survey included a sample of 5.5 million, but little is known
      about its potential utility in informing developments aimed at improving the
      quality of patients' experiences of primary care. AIM: To investigate primary
      care providers' response to feedback on patient experience from a national
      survey. DESIGN AND SETTING: Qualitative interview study in 10 general practices
      from four primary care trusts in England. METHOD: Semi-structured interviews were
      conducted with GPs, practice nurses, and practice managers (n = 37). Transcripts
      were analysed thematically. RESULTS: Although some participants reported making
      changes to their practice in response to the survey data, many expressed doubts
      about the credibility of the results. Key issues included: concerns about
      practical aspects of the survey, such as the response rate and representativeness
      of the sample; the view that it gave insufficient detail to facilitate change and
      failed to address some salient issues; and unease about the influence of
      political influences underpinning its introduction and use. CONCLUSION: Although,
      in general, primary care professionals have positive attitudes towards patient
      feedback, this study suggests a mismatch between the conventional demonstration
      of the objectivity of a questionnaire survey and the attitudes and experiences of
      those receiving the data. This is likely to prevent doctors from engaging
      constructively with the survey. These concerns may well militate against the
      potential of the survey to act as a simple means of capturing, and effectively
      using, feedback from patients.

PMID- 23561788
TI  - Understanding of family medicine in Africa: a qualitative study of leaders'
      views.
AB  - BACKGROUND: The World Health Organization encourages comprehensive primary care
      within an ongoing personalised relationship, including family physicians in the
      primary healthcare team, but family medicine is new in Africa, with doctors
      mostly being hospital based. African family physicians are trying to define
      family medicine in Africa, however, there is little clarity on the views of
      African country leadership and their understanding of family medicine and its
      place in Africa. AIM: To understand leaders' views on family medicine in Africa.
      DESIGN AND SETTING: Qualitative study with in-depth interviews in nine sub
      Saharan African countries. METHOD: Key academic and government leaders were
      purposively selected. In-depth interviews were conducted using an interview
      guide, and thematically analysed. RESULTS: Twenty-seven interviews were conducted
      with government and academic leaders. Responders saw considerable benefits but
      also had concerns regarding family medicine in Africa. The benefits mentioned
      were: having a clinically skilled all-rounder at the district hospital; mentoring
      team-based care in the community; a strong role in leadership and even management
      in the district healthcare system; and developing a holistic practice of
      medicine. The concerns were that family medicine is: unknown or poorly understood
      by broader leadership; poorly recognised by officials; and struggling with policy
      ambivalence, requiring policy advocacy championed by family medicine itself.
      CONCLUSION: The strong district-level clinical and leadership expectations of
      family physicians are consistent with African research and consensus. However,
      leaders' understanding of family medicine is couched in terms of specialties and
      hospital care. African family physicians should be concerned by high expectations
      without adequate human resource and implementation policies.

PMID- 23561789
TI  - Burnout among French GPs in training: a cross-sectional study.
AB  - BACKGROUND: French GPs in training have an important role in making hospitals
      function and are the future workforce, however burnout among this group is not
      uncommon. AIM: To assess burnout among French trainees. DESIGN AND SETTING:
      Descriptive, epidemiological, transverse cross-sectional study in France. METHOD:
      All 6309 French trainees attending a meeting to choose their next 6-month
      placement (March 2011), were invited to complete a written questionnaire
      including the Maslach Burnout Inventory, items about their health, and how they
      felt about medical internship. RESULTS: A total of 4050 anonymous questionnaires
      were analysed (response rate: 64.2%). The percentage of trainees with high levels
      of emotional exhaustion was 16.0%, 33.8% had a high score for depersonalisation,
      and 38.9% had a high score for low personal accomplishment. A total of 41.9% had
      no high score at all and 6.5% (n = 283) presented three high scores. Notable
      associations were found between burnout and workload, lack of acknowledgement for
      trainees' work, working in accident and emergency departments, and lack of time
      devoted to private life. CONCLUSION: This is the first French national survey
      about burnout in French GP trainees. It confirms the findings of previous French
      regional studies, which showed an increased rate of depersonalisation but
      decreased rates of emotional exhaustion. Trainees play an important role in the
      French health system: they represent tomorrow's doctors, so these results are
      worrying for the French public-health system. They imply a need for action by
      doctors, professional bodies, and healthcare organisations. A few preventive
      measures could be tested, such as creating an employment contract for trainees,
      helping trainees to assume responsibilities step by step, and putting more
      thought into training in outpatient clinics.

PMID- 23561790
TI  - Development of an instrument for the identification of frail older people as a
      target population for integrated care.
AB  - BACKGROUND: Primary care is increasingly interested in the identification of
      frailty, as it selects the target population for integrated care. However,
      instruments for the identification of frailty specifically validated for use in
      primary care are scarce. This study developed the Easycare Two-step Older persons
      Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic
      screening procedure to identify frail older people. AIM: This paper aims to
      describe the development of the Easycare-TOS and the data from the pilot studies.
      DESIGN AND SETTING: Observational pilot study in seven academic GP practices in
      and around Nijmegen, The Netherlands. METHOD: The Easycare-TOS was developed in a
      cyclic process with the input of stakeholders. In every cycle, the requirements
      were first defined, then translated into a prototype that was tested in a pilot
      study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the
      professionals' appraisal is decisive in the frailty decision, instead of a cut
      off score. Further, it considers aspects of frailty, as well as aspects of the
      care context of the patient. RESULTS: The pilot data have shown that after step
      1, two-thirds of the patients do not need further assessment, because they are
      judged as not frail, based on prior knowledge of the GP. The overall prevalence
      of frailty in this pilot study is 24%. Most professionals who participated in the
      pilot studies considered the time investment acceptable and the method to be of
      added value. CONCLUSION: The Easycare-TOS instrument meets the predefined
      efficiency, flexibility, and acceptability requirements for use as an
      identification instrument for frailty in primary care.

PMID- 23561792
TI  - Sports hernia: a clinical update.

PMID- 23561791
TI  - The James Mackenzie Lecture 2012: bothering about Billy.

PMID- 23561793
TI  - Susceptibility-weighted imaging for cerebral microbleed detection in super-acute
      ischemic stroke patients treated with intravenous thrombolysis.
AB  - OBJECTIVE: Fast magnetic resonance imaging (MRI) and susceptibility-weighted
      imaging (SWI) methods may provide more accurate detection of the highly variant
      time window for successful intravenous (IV) thrombolytic drug treatment
      (averaging 3 hours) for cerebral microbleeds (CMBs) in acute stroke patients.
      METHODS: This prospective study applies fast MRI and SWI for examination of 279
      prescreened ischemic stroke patients within 12 hours of stroke onset. One hundred
      and sixty-two (58.1%) of 279 patients were diagnosed with super-acute ischemic
      stroke with restricted diffusion, hyperintense diffusion-weighted imaging
      signals, and no ischemic change in T2-weighted imaging, fluid-attenuated
      inversion recovery, or T1-weighted imaging signals. Recombinant tissue
      plasminogen activator IV thrombolysis was administered to 113 (69.75%) patients
      (thrombolysis group). All patients underwent regular sequence MRI and SWI follow
      up. RESULTS: Computed tomography and MRI sequence scans revealed hemorrhagic
      transformations in 13 (11.50%) thrombolysis and four (8.16%) non-thrombolysis
      group patients. MRI-guided thrombolysis treatment produced no significant
      differences between the two groups. SWI revealed new CMBs in 46 (40.70%) and nine
      (18.37%) thrombolysis and non-thrombolysis group patients, respectively.
      Significantly better National Institutes of Health stroke scale (24 hours)
      (P<0.05), modified Rankin scale (90 days) (P<0.01), and life quality Barthal
      index scores were observed in CMB patients (P<0.01). CONCLUSIONS: SWI revealed
      higher CMB incidence and clinical improvement in recombinant tissue plasminogen
      activator IV thrombolysis-treated super-acute ischemic stroke patients,
      suggesting that CMBs may indicate vascular re-canalization/reperfusion. Thus, SWI
      can be applied to extend individual patient windows for thrombolytic treatment
      beyond general recommendations of treatment within 3 hours, allowing treatment up
      to 12 hours from stroke onset.

PMID- 23561794
TI  - Molecular imaging: the key to advancing cardiac stem cell therapy.
AB  - Cardiac stem cell therapy continues to hold promise for the treatment of ischemic
      heart disease despite the fact that early promising pre-clinical findings have
      yet to be translated into consistent clinical success. The latest human studies
      have collectively identified a pressing need to better understand stem cell
      behavior in humans and called for more incorporation of noninvasive imaging
      techniques into the design and evaluation of human stem cell therapy trials. This
      review discusses the various molecular imaging techniques validated to date for
      studying stem cells in living subjects, with a particular emphasis on their
      utilities in assessing the acute retention and the long-term survival of
      transplanted stem cells. These imaging techniques will be essential for advancing
      cardiac stem cell therapy by providing the means to both guide ongoing
      optimization and predict treatment response in humans. 

PMID- 23561795
TI  - Elastin fragmentation and atherosclerosis progression: the elastokine concept.
AB  - Atherosclerosis is a progressive multifaceted inflammatory disease affecting
      large- and medium-sized arteries. Typical feature of this disease is the
      formation and build-up of atherosclerotic plaques characterized by vascular
      extracellular matrix degradation and remodeling. Many studies have documented
      degradation of native elastin, the main extracellular matrix protein responsible
      for resilience and elasticity of arteries, by local release of elastases, leading
      to the production of elastin-derived peptides (EDP). These peptides have been
      proposed to actively participate in the progression of the disease by
      accelerating different biological processes, such as LDL oxidation and
      calcification of the vascular wall. These pathophysiological effects are mediated
      by the binding of EDP on a peculiar heterotrimeric receptor named elastin
      receptor complex (ERC). In this article, we review the contribution of elastin in
      biological processes involved in atherosclerosis progression from its initial
      elastase-driven degradation to its ultimate cellular effects. Finally, we discuss
      the ERC and its derived signaling pathways as promising therapeutic targets. 

PMID- 23561796
TI  - Technical specifications for mechanical recycling of agricultural plastic waste.
AB  - Technical specifications appropriate for the recycling of agricultural plastic
      wastes (APWs), widely accepted by the recycling industry were developed. The
      specifications establish quality standards to be met by the agricultural plastics
      producers, users and the agricultural plastic waste management chain. They
      constitute the base for the best economical and environmental valorisation of the
      APW. The analysis of the APW streams conducted across Europe in the framework of
      the European project "LabelAgriWaste" revealed the inherent characteristics of
      the APW streams and the inherent constraints (technical or economical) of the
      APW. The APW stream properties related to its recycling potential and measured
      during pilot trials are presented and a subsequent universally accepted
      simplified and expanded list of APW recycling technical specifications is
      proposed and justified. The list includes two sets of specifications, applied to
      two different quality categories of recyclable APW: one for pellet production
      process ("Quality I") and another one for plastic profile production process
      ("Quality II"). Parameters that are taken into consideration in the
      specifications include the APW physical characteristics, contamination,
      composition and degradation. The proposed specifications are focused on
      polyethylene based APW that represents the vast majority of the APW stream.
      However, the specifications can be adjusted to cover also APW of different
      materials (e.g. PP or PVC) that are found in very small quantities in protected
      cultivations in Europe. The adoption of the proposed specifications could
      transform this waste stream into a labelled commodity traded freely in the market
      and will constitute the base for the best economical and environmental
      valorisation of the APW.

PMID- 23561797
TI  - Quantifying capital goods for waste incineration.
AB  - Materials and energy used for the construction of modern waste incineration
      plants were quantified. The data was collected from five incineration plants
      (72,000-240,000 tonnes per year) built in Scandinavia (Norway, Finland and
      Denmark) between 2006 and 2012. Concrete for the buildings was the main material
      used amounting to 19,000-26,000 tonnes per plant. The quantification further
      included six main materials, electronic systems, cables and all transportation.
      The energy used for the actual on-site construction of the incinerators was in
      the range 4000-5000 MW h. In terms of the environmental burden of producing the
      materials used in the construction, steel for the building and the machinery
      contributed the most. The material and energy used for the construction
      corresponded to the emission of 7-14 kg CO2 per tonne of waste combusted
      throughout the lifetime of the incineration plant. The assessment showed that,
      compared to data reported in the literature on direct emissions from the
      operation of incinerators, the environmental impacts caused by the construction
      of buildings and machinery (capital goods) could amount to 2-3% with respect to
      kg CO2 per tonne of waste combusted.

PMID- 23561798
TI  - Antimony leaching in plastics from waste electrical and electronic equipment
      (WEEE) with various acids and gamma irradiation.
AB  - There has been a recent interest in antimony since the availability in readily
      mined areas is decreasing compared to the amounts used. It is important in many
      applications such as flame retardants and in the production of polyester, which
      can trigger an investigation of the leachability of antimony from plastics using
      different acids. In this paper, different types of acids are tested for their
      ability to leach antimony from a discarded computer housing, made of
      poly(acrylonitrile butadiene styrene), which is a common plastic type used in
      electrical and electronic equipment. The acid solutions included sodium hydrogen
      tartrate (0.5M) dissolved in either dimethyl sulfoxide or water (at ca. 23
      degrees C and heated to ca. 105 degrees C). The metal content after leaching was
      determined by inductively coupled plasma optical emission spectroscopy. The most
      efficient leaching medium was the heated solution of sodium hydrogen tartrate in
      dimethyl sulfoxide, which leached almost half of the antimony from the
      poly(acrylonitrile butadiene styrene). Gamma irradiation, which is proposed to
      improve the mechanical properties in plastics, was used here to investigate the
      influence of antimony leaching ability. No significant change in the amount of
      leached antimony could be observed.

PMID- 23561799
TI  - A novel nanobody against urease activity of Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori infection is associated with gastritis and in
      some cases with gastric and duodenal ulcers, and even adenocarcinoma. Antibiotic
      therapy has significant limitations, such as the high cost and the emergence of
      antibiotic-resistant strains, generating the need for new treatments. The
      administration of antibody against H. pylori is a new effective therapeutic
      strategy. In this study, we successfully developed a single-variable domain of
      heavy chain antibody against recombinant UreC. METHODS: A VHH phagemid library
      was constructed from immune camel heavy chain antibodies. The nanobodies were
      displayed on M13 phage. Library selection was performed against UreC recombinant
      protein. A specific single-variable domain of heavy chain antibody against UreC
      was screened in five rounds of panning. The nanobody with the highest score in
      the phage ELISA was selected for soluble expression. The nanobody was purified
      with a nickel-nitrilotriacetic acid (Ni-NTA) column and confirmed with sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western
      blotting. Affinity, specificity, and urease inhibitory properties of the nanobody
      were assayed. RESULTS: Here we showed the isolation and purification of a
      specific nanobody with high affinity against UreC recombinant protein that can
      inhibit urease activity. CONCLUSIONS: The isolated UreC nanobody can specifically
      detect and bind to UreC and inhibit urease activity. This nanobody could be a
      novel class of treatment measure against H. pylori infection.

PMID- 23561800
TI  - Evidence mounts that viruses drive atopic development.

PMID- 23561801
TI  - Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection
      interact to predispose toward the development of asthma-like pathology in mice.
AB  - BACKGROUND: Respiratory tract viruses are a major environmental risk factor for
      both the inception and exacerbations of asthma. Genetic defects in Toll-like
      receptor (TLR) 7-mediated signaling, impaired type I interferon responses, or
      both have been reported in asthmatic patients, although their contribution to the
      onset and exacerbation of asthma remains poorly understood. OBJECTIVE: We sought
      to determine whether Pneumovirus infection in the absence of TLR7 predisposes to
      bronchiolitis and the inception of asthma. METHODS: Wild-type and TLR7-deficient
      (TLR7(-/-)) mice were inoculated with the rodent-specific pathogen pneumonia
      virus of mice at 1 (primary), 7 (secondary), and 13 (tertiary) weeks of age, and
      pathologic features of bronchiolitis or asthma were assessed. In some experiments
      infected mice were exposed to low-dose cockroach antigen. RESULTS: TLR7
      deficiency increased viral load in the airway epithelium, which became sloughed
      and necrotic, and promoted an IFN-alpha/beta(low), IL-12p70(low), IL-1beta(high),
      IL-25(high), and IL-33(high) cytokine microenvironment that was associated with
      the recruitment of type 2 innate lymphoid cells/nuocytes and increased TH2-type
      cytokine production. Viral challenge of TLR7(-/-) mice induced all of the
      cardinal pathophysiologic features of asthma, including tissue eosinophilia, mast
      cell hyperplasia, IgE production, airway smooth muscle alterations, and airways
      hyperreactivity in a memory CD4(+) T cell-dependent manner. Importantly,
      infections with pneumonia virus of mice promoted allergic sensitization to
      inhaled cockroach antigen in the absence but not the presence of TLR7.
      CONCLUSION: TLR7 gene defects and Pneumovirus infection interact to establish an
      aberrant adaptive response that might underlie virus-induced asthma exacerbations
      in later life.

PMID- 23561802
TI  - Peripheral lung function in patients with stable and unstable asthma.
AB  - BACKGROUND: Exacerbations of asthma are thought to be caused by airflow
      obstruction resulting from airway inflammation, bronchospasm, and mucus plugging.
      Histologic evidence suggests the small airways, including acinar air spaces, are
      involved; however, this has not been corroborated in vivo by measurements of
      peripheral small-airway function. OBJECTIVE: We sought to determine whether
      asthma severity is linked to small-airway function, particularly in patients with
      acute severe asthma. METHODS: Eighteen subjects admitted for an asthma
      exacerbation underwent lung function testing, including measures of acinar
      ventilation heterogeneity (S(acin)) and conductive ventilation heterogeneity
      (S(cond)) using the multiple-breath nitrogen washout. Treatment requirement was
      defined according to Global Initiative for Asthma scores. Data were compared with
      those obtained in 19 patients with stable asthma. RESULTS: For the asthma
      exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to
      75% of predicted value), the median S(cond) value was 185% of predicted value
      (95% CI, 119% to 245% of predicted value), and the median S(acin) value was 225%
      of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent
      predicted) was correlated with S(acin) (percent predicted) values (Spearman rho =
      -0.67, P = .006) but not with S(cond) (percent predicted) values (P > .1). The
      Global Initiative for Asthma score was significantly related to S(acin) (percent
      predicted) (Spearman rho = 0.59, P = .016) but not to S(cond) (percent predicted)
      values (P > .1). The unstable group was characterized by considerably lower
      forced vital capacity (P < .001) and higher S(cond) (P = .001) values than the
      unstable group. In a subgroup of 11 unstable patients who could be reviewed after
      4 weeks, FEV1, forced vital capacity, S(acin), and S(cond) values showed marked
      improvements. CONCLUSION: Our findings suggest that unstable asthma is
      characterized by a combined abnormality in the acinar and conductive lung zones,
      both of which are partly reversible. Functional abnormality in the acinar lung
      zone in particular showed a direct correlation with airflow obstruction and
      treatment requirement in patients with acute severe asthma.

PMID- 23561803
TI  - Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation
      to severe combined immunodeficiency.
AB  - BACKGROUND: Primary immunodeficiencies represent model diseases for the
      mechanistic understanding of the human innate and adaptive immune response. They
      are clinically highly relevant per se because in patients with severe combined
      immunodeficiency (SCID), infections caused by opportunistic pathogens are
      typically life-threatening early in life. OBJECTIVES: We aimed at defining and
      functionally characterizing a novel form of SCID in an infant of consanguineous
      parents who presented with life-threatening Pneumocystis jirovecii pneumonia
      using a comprehensive immunologic and whole-exome genetic diagnostic strategy.
      METHODS: Analysis of leukocyte subpopulations was performed by using multicolor
      flow cytometry and was combined with stimulation tests for T-cell function. The
      search for a disease-causing mutation was performed with diagnostic whole-exome
      sequencing and systematic variant categorization. Reconstitution assays were used
      for validating the loss-of-function mutation. RESULTS: The novel entity of SCID
      was characterized by agammaglobulinemia and profoundly deficient T-cell function
      despite quantitatively normal T and B lymphocytes. Genetic analysis revealed a
      single pathogenic homozygous nonsense mutation of the caspase recruitment domain
      11 (CARD11) gene. In reconstitution assays we demonstrated that the patient
      derived truncated CARD11 protein is defective in antigen receptor signaling and
      nuclear factor kappaB activation. CONCLUSION: We show that an inactivating CARD11
      mutation links defective nuclear factor kappaB signaling to a novel cause of
      autosomal recessive SCID.

PMID- 23561804
TI  - Outcomes in patients who have failed endoscopic therapy for dysplastic Barrett's
      metaplasia or early esophageal cancer.
AB  - BACKGROUND: Endoscopic therapy (ablation +/- mucosal resection) for esophageal
      high-grade dysplasia (HGD) or intramucosal carcinoma has demonstrated promising
      results. Little is known about patients who have persistent or progressive
      disease despite endotherapy. We compared patients who had successful eradication
      of their disease with those in whom endotherapy failed to try to identify factors
      predictive of failure and outcomes after salvage therapy. METHODS: We performed a
      single-institution retrospective review of patients treated with endotherapy from
      2007 to 2012. RESULTS: Thirty-eight patients underwent endotherapy: 28 had
      successful eradication of their disease and endotherapy failed in 10 patients.
      Patients in whom endotherapy failed were more likely to have high-grade dysplasia
      (HGD) on initial endoscopy, nodules or ulcers, multifocal dysplasia, and
      persistent nondysplastic Barrett's metaplasia. Patients in whom endotherapy
      failed also underwent significantly more endotherapy sessions. Seven patients had
      persistent dysplasia or progression to cancer, and 3 patients had complete
      eradication of HGD but presented with intramucosal carcinoma an average of 15
      months after eradication. The 10 patients in whom endotherapy failed underwent
      salvage therapy with esophagectomy (7 patients), definitive chemoradiotherapy (1
      patient), and endotherapy (2 patients). Patients treated with esophagectomy were
      disease free at a mean of 25 months postoperatively. CONCLUSIONS: HGD on initial
      endoscopy, multifocal dysplasia, mucosal abnormalities, and failure to eradicate
      nondysplastic Barrett's metaplasia were associated with failure of endotherapy.
      Patients with these characteristics should be considered at higher risk for
      treatment failure, and earlier consideration should be given to esophagectomy if
      there is persistent, progressive, or recurrent neoplasia. Clinical outcomes are
      good, even after salvage therapy. Continued endoscopic surveillance is mandatory
      after successful endotherapy because of the risk of recurrent disease.

PMID- 23561805
TI  - Rapamycin blocks fibrocyte migration and attenuates bronchiolitis obliterans in a
      murine model.
AB  - BACKGROUND: Fibrocytes are integral in the development of fibroproliferative
      disease. The CXCL12/CXCR4 chemokine axis has been shown to play a central role in
      fibrocyte migration and the development of bronchiolitis obliterans (BO) after
      lung transplantation. Inhibition of the mammalian target of rapamycin (mTOR)
      pathway with rapamycin has been shown to decrease expression of both CXCR4 and
      its receptor agonist CXCL12. Thus, we hypothesized that rapamycin treatment would
      decrease fibrocyte trafficking into tracheal allografts and prevent BO. METHODS:
      A total alloantigenic mismatch murine heterotopic tracheal transplant (HTT) model
      of BO was used. Animals were either treated with rapamycin or dimethyl sulfoxide
      (DMSO) for 14 days after tracheal transplantation. Fibrocyte levels were assessed
      by flow cytometry, and allograft neutrophil, CD3(+) T-cell, macrophage, and
      smooth muscle actin (SMA) levels were assessed by immunohistochemistry. Tracheal
      luminal obliteration was assessed on hematoxylin and eosin (H&E) stains. RESULTS:
      Compared with DMSO-treated controls, rapamycin-treated mice showed a significant
      decrease in fibrocyte levels in tracheal allografts. Fibrocyte levels in
      recipient blood showed a similar pattern, although it was not statistically
      significant. Furthermore, animals treated with rapamycin showed a significant
      decrease in tracheal allograft luminal obliteration compared with controls. Based
      on immunohistochemical analyses, populations of alpha-SMA-positive (alpha-SMA(+))
      cells, neutrophils, CD3(+) T cells, and macrophages were all decreased in
      rapamycin-treated allografts versus DMSO controls. CONCLUSIONS: Rapamycin
      effectively reduces recruitment of fibrocytes into tracheal allografts and
      mitigates development of tracheal luminal fibrosis. Further studies are needed to
      determine the cellular and molecular mechanisms that mediate the protective
      effect of rapamycin against BO.

PMID- 23561806
TI  - Does bilobectomy offer satisfactory long-term survival outcome for non-small cell
      lung cancer?
AB  - BACKGROUND: Results of bilobectomy for non-small cell lung cancer have rarely
      been studied. METHODS: Retrospective analysis was conducted on patients with non
      small cell lung cancer having undergone bilobectomy from January 1999 to June
      2012 at our institution. Analysis aimed at determining perioperative mortality
      and morbidity, and at studying prognostic factors for long-term survival using
      the 7th TNM classification. RESULTS: A total of 103 patients (85 males; mean age
      62 years) underwent upper-middle bilobectomy (n = 54) or lower-middle bilobectomy
      (n = 49). Histologic examination revealed 51 adenocarcinomas, 43 squamous cell
      carcinomas and 9 other cell carcinomas. Perioperative mortality was 0.97%. The
      overall morbidity rate was 71%, whereas the rate of life-threatening
      complications was 9.6%. Complications were more frequent in men (p = 0.032), in
      patients with chronic pulmonary obstructive diseases (p = 0.030) and after lower
      middle bilobectomy (p = 0.0016). The overall 5-year Kaplan-Meier survival rate
      was 57.8%. In univariate analysis, factors associated with increased survival
      were the following: pathologic stage (stage I 74.9%, stage II 64.1%, stage III
      28.8%, p = 0.0018); nodal status (N0 vs N1, p = 0.011; N0 vs N2, p = 0.0015; N0
      vs N+, p = 0.0008); R status (R0 vs R1, p = 0.0032), and smoking status (past
      smoker or nonsmoker vs active smoker, p = 0.00054). Multivariate analysis
      revealed that active smokers (RR = 3.87, CI 95% [1.83 to 8.21]; p = 0.00042) and
      increasing stage (stage 0: RR=1; stage I: RR = 1.98, CI 95% [1.38 to 2.83]; stage
      II: RR = 3.90, CI 95% [1.90 to 8.02]; stage III: RR=7.72, CI 95% [2.62 to 22.73];
      stage IV: RR = 15.25, CI 95% [3.61 to 64.40]; p = 0.0042) were significantly
      associated with poorer survival. CONCLUSIONS: Bilobectomy can be performed with
      low mortality, acceptable morbidity and long term survival in accordance with TNM
      staging.

PMID- 23561807
TI  - Pediatric heart transplantation for congenital and restrictive cardiomyopathy.
AB  - BACKGROUND: Recent reports suggest worse outcomes in pediatric orthotopic heart
      transplantation (OHT) for congenital heart disease (CHD) and restrictive
      cardiomyopathy (RCM). We examined early outcomes in these diverse groups of
      patients in comparison with patients with dilatated cardiomyopathy (DCM).
      METHODS: From 2000 to 2011, 209 patients were included: 50 with CHD, 23 with RCM,
      and 136 with DCM. Early survival was studied, as was the occurrence of acute
      rejection, donor-specific antibodies (DSAs) and nondonor-specific antibodies
      (NSDAs), incidence of pulmonary hypertension (PHT), right ventricular failure
      (RVF), and the need for mechanical circulatory support (MCS). RESULTS: The
      incidence of preoperative PHT was greatest in the RCM group (chi(2)p = 0.0006);
      the requirement for mechanical support before OHT was greatest in patients with
      DCM. Thirty-day survival was 92.0%, 97.1%, and 100% for patients with CHD, DCM,
      and RCM respectively. The incidence of RVF was highest for patients with RCM
      (43.5%; versus CHD, 26.0%; versus DCM, 14.7%). One-year survival estimates for
      patients with CHD, DCM, and RCM were 92.0%, 97.8%, and 82.6%, respectively (log
      rank p = 0.165). Multivariable analysis revealed 4 significant risk factors for
      mortality: age, incidence of acute rejection, preoperative PHT, and the presence
      of NDSAs. The occurrence of DSAs was similar, although there was a significantly
      higher incidence of NDSAs in the CHD and RCM groups (36.0% and 30.4%,
      respectively, versus 14.0% in the DCM group; chi(2)p = 0.0024). CONCLUSIONS:
      Equivalent outcomes are achievable in pediatric OHT despite marked heterogeneity
      in anatomic and physiologic complexity in recipients. Physiologic factors such as
      PHT are likely to be more important than anatomic complexities in determining
      survival. The potential relevance of NDSAs warrants further investigation.

PMID- 23561808
TI  - The antifungal activity of the cuticular and internal fatty acid methyl esters
      and alcohols in Calliphora vomitoria.
AB  - SUMMARY The composition of the fatty acid methyl ester (FAME) and alcohol
      fractions of the cuticular and internal lipids of Calliphora vomitoria larvae,
      pupae and male/female adults was obtained by separating these two fractions by
      HPLC-LLSD and analysing them quantitatively using GC-MS. Analysis of the
      cuticular lipids of the worldwide, medically important ectoparasite C. vomitoria
      revealed 6 FAMEs with odd-numbered carbon chains from C15:0 to C19:0 in the
      larvae, while internal lipids contained 9 FAMEs ranging from C15:1 to C19:0.
      Seven FAMEs from C15:0 to C19:0 were identified in the cuticular lipids of the
      pupae, whereas the internal lipids of the pupae contained 10 FAMEs from C13:0 to
      C19:0. The cuticular lipids of males and females and also the internal lipids of
      males contained 5, 7 and 6 FAMEs from C15:0 to C19:0 respectively. Seven FAMEs
      from C13:0 to C19:0 were identified in the internal lipids of females, and 7, 6,
      5 and 3 alcohols were found in the cuticular lipids of larvae, pupae, males and
      females respectively. Only saturated alcohols with even-numbered carbon chains
      were present in these lipids. Only 1 alcohol (C22:0) was detected in the internal
      lipids of C. vomitoria larvae, while just 4 alcohols from - C18:0 to C24:0 - were
      identified in the internal lipids of pupae, and males and females. We also
      identified glycerol and cholesterol in the larvae, pupae, males and females of C.
      vomitoria. The individual alcohols and FAMEs, as well as their mixtures isolated
      from the cuticular and internal lipids of larvae, pupae, males and females of C.
      vomitoria, demonstrated antimicrobial activity against entomopathogenic fungi.

PMID- 23561811
TI  - Individualized approach in the management of patients with hypoplastic left heart
      syndrome (HLHS).
AB  - Over the past decade new variations on the "classic" first stage palliation (the
      Norwood/BT shunt) for patients with Hypoplastic Left Heart Syndrome have emerged
      and been vetted by the medical community. A "one size fits all" approach may not
      be adequate anymore. In this review, the optimal indications for the various
      palliative options (Norwood/BT shunt, Norwood/RV-PA conduit, Hybrid Stage I with
      or without ductal stenting, heart transplantation) are reviewed from a standpoint
      of the initial anatomy and physiology of the patient, letting it guide clinical
      management. Current knowledge useful for decision-making is also reviewed as
      objectively as possible.

PMID- 23561812
TI  - Pitfalls in repair of conotruncal anomalies.
AB  - Despite a wide anatomic diversity, the complete repair of all conotruncal
      anomalies includes two surgical steps. 1) An intracardiac tunnel is created to
      connect the left ventricle to one of the arterial orifices (usually the aortic,
      sometimes the pulmonary), through the conoventricular ventricular septal defect.
      Any conal septum should be resected to create a short, large, and straight
      tunnel. Abnormal insertions of the atrioventricular valves (tricuspid and mitral)
      on the conal septum should be preserved. "Intramural" residual ventricular septal
      defects must be avoided by anchoring the intracardiac patch directly to the
      arterial annulus. 2) To connect the right ventricle to the pulmonary artery,
      either an intracardiac or an extracardiac reconstruction is carried out,
      according to the distance between the tricuspid valve and the pulmonary orifice.
      When extracardiac reconstruction is indicated, it is usually performed without
      prosthetic conduit (with or without French maneuver, eventually using the left
      atrial appendage). In most patients, complete repair can be performed as a
      primary operation during infancy.

PMID- 23561813
TI  - Low birth weight and very low birth weight neonates with congenital heart
      disease: timing of surgery, reasons for delaying or not delaying surgery.
AB  - Conventional management of low birth weight and very low birth weight neonates
      was composed of deferring corrective surgery by aggressive medical management or
      palliative surgery which does not require cardiopulmonary bypass. However, while
      waiting for weight gain, these neonates are at risk for various comorbidities. In
      the current era, this "wait and let the baby grow" approach has not been shown to
      result in better clinical outcomes. Early primary repair hence has become the
      standard strategy for congenital heart disease requiring surgery in these
      neonates. However, there still exist some circumstances, which are considered to
      be unfavorable for corrective surgery due to medical, physiologic, surgeon's
      technical and institutional-systemic factors. We reviewed the recent literature
      and examined the reasons for delaying or not delaying surgery.

PMID- 23561814
TI  - Neonatal cardiac care, a perspective.
AB  - Every year in the United States approximately 40,000 infants are born with
      congenital heart disease. Several of these infants require corrective or
      palliative surgery in the neonatal period. Mortality rates after cardiac surgery
      are highest amongst neonates, particularly those born prematurely. There are
      several reasons for the increased surgical mortality risk in neonates. This
      review outlines these risks, with particular emphasis on the relative immaturity
      of the organ systems in the term and preterm neonate.

PMID- 23561815
TI  - Unbalanced atrioventricular septal defect: defining the limits of biventricular
      repair.
AB  - Unbalanced atrioventricular septal defect (uAVSD) is a challenging lesion with
      suboptimal outcomes in the current era. Severe forms of uAVSD mandate
      univentricular repair with well-documented outcomes. Determining the feasibility
      of biventricular repair (BVR) in patients with moderate forms of uAVSD is
      difficult. Ventricular hypoplasia has traditionally formed the cornerstone of
      defining uAVSD. However, malalignment of the atrioventricular junction and
      related derangements of the anatomy and physiology of the atrioventricular inflow
      play a central role in establishing and sustaining a biventricular end state.
      Atrioventricular valve index, left ventricular inflow index, and right
      ventricle/left ventricle inflow angle are important recently described measures
      of inflow physiology. Additional patient anatomic and physiologic factors that
      impact BVR feasibility undoubtedly exist. A recently launched Congenital Heart
      Surgeons Society prospective inception cohort study will address these and other
      issues that impair our ability to predict BVR feasibility in uAVSD.

PMID- 23561816
TI  - Strategies to maintain biventricular circulation in patients with high-risk
      anatomy.
AB  - Although hypoplasia of left heart structures presents with a spectrum of
      severity, management decisions are typically dichotomous: single-ventricle
      palliation or biventricular repair. Since the long-term outcomes of single
      ventricle palliation are sub-optimal, strategies to aggressively pursue
      biventricular circulation in patients with borderline left heart structures have
      been developed. Recent strategies and surgical techniques to rehabilitate the
      left heart in patients with borderline left heart are described.

PMID- 23561817
TI  - The neonatal hypoplastic aortic arch: decisions and more decisions.
AB  - Neonatal patients with hypoplasia of the aortic arch constitute a heterogeneous
      group with a wide spectrum of severity. The milder end of the spectrum comprises
      patients with aortic coarctation and isthmus hypoplasia. At the other end of the
      spectrum are patients with severe transverse arch hypoplasia or hypoplastic left
      heart syndrome. The aim of this paper is to discuss the various strategies and
      surgical approaches available for this group of patients, focusing on the
      surgical decisions that influence individual patient management. Many of the
      things discussed are applicable to any neonatal arch problem. We also describe
      and discuss in detail our surgical technique for patients who undergo neonatal
      repair of a hypoplastic aortic arch via median sternotomy.

PMID- 23561818
TI  - The Norwood procedure: in favor of the RV-PA conduit.
AB  - Evolution of the Norwood procedure has culminated in there currently being three
      treatment strategies available for initial management: the 'classical' Norwood
      (utilizing a Blalock-Taussig shunt), the Norwood with right-ventricle to
      pulmonary artery (RV-PA) conduit, and the 'hybrid' Norwood procedure utilizing
      bilateral pulmonary artery banding and ductal stenting. Each variant has its
      potential advantages and disadvantages, and this paper looks to examine the
      evidence in favor of each strategy, with emphasis on the supportive data for the
      RV-PA conduit. The 'classical' procedure has the benefit of the greatest
      accumulated surgical experience and avoids any incision into the ventricle.
      However, the diastolic run-off of the Blalock-Taussig shunt can cause hemodynamic
      instability and unpredictable coronary steal phenomenon. The RV-PA conduit has
      the advantage of maintaining diastolic pressure with a more stable postoperative
      course, but at the cost of a ventriculotomy that may have detrimental long-term
      sequelae. The 'hybrid' procedure has the advantage of avoiding cardiopulmonary
      bypass, but does not always secure coronary blood flow and has a high inter-stage
      morbidity and reintervention rate. The evidence shows that each technique may
      have its place in future management, and that treatment algorithms could emerge
      that direct the choice of procedure for specific patient groups.

PMID- 23561820
TI  - In favor of the Hybrid Stage 1 as the initial palliation for hypoplastic left
      heart syndrome.
AB  - There are many reasons to consider using the Hybrid Stage 1 procedure as the
      initial palliation for hypoplastic left heart syndrome. It allows all options for
      treatment, including a delayed traditional approach, as well as a platform to
      evolve our overall approach to this challenging heart defect.

PMID- 23561819
TI  - Neonatal cardiopulmonary bypass.
AB  - Cardiac surgery with cardiopulmonary bypass is routinely used in neonates who
      require early repair of congenital heart diseases. However, the bypass
      temperature and use of deep hypothermic circulatory arrest, the composition of
      the priming and the acceptable degree of hemodilution, the prophylactic use of
      antifibrinolytic agents and steroids, the choice of myocardial protection, the
      best PaO2, and even the pump flow, are still subjects of debate, despite major
      improvements in neonatal bypass over the last decade. Nevertheless, there are
      some techniques that have reached a near-consensus and are highly recommended in
      neonates: the use of minaturized bypass circuits to reduce blood product
      transfusions and inflammation, ultrafiltration, and the continuous monitoring of
      mixed venous and regional oxygen saturations to assess adequacy of perfusion.
      Nevertheless, surprisingly many different techniques may lead to the same results
      and mortality rate. As operative mortality rates have declined, the comparison
      endpoints between techniques have moved and focus on morbidity rates, extubation
      delay, ICU and hospital length of stay; in other words, the cost and (of course)
      the late functional outcome are certainly the new goals of neonatal
      cardiopulmonary bypass.

PMID- 23561821
TI  - Adsorption of carbon dioxide on Al/Fe oxyhydroxide.
AB  - The structure and reactivity of 0-70mol% Al/Fe iron oxyhydroxides (ferrihydrite
      in the absence and presence of Al) toward gaseous CO2 were investigated with X
      ray photoelectron spectroscopy (XPS), atomic absorption (AA), scanning
      transmission electron microscopy with electron dispersive X-ray spectroscopy
      (STEM/EDS), X-ray diffraction (XRD), and attenuated total reflectance Fourier
      transform Infrared spectroscopy (ATR-FTIR) combined with density functional
      theory (DFT) calculations. Results showed that Al/Fe oxyhydroxide particles
      containing more than 20 mol% Al consisted at least in part of Fe-oxyhydroxide
      with incorporated Al and a discrete AlOOH phase. Results from ATR-FTIR
      experiments and DFT calculations suggested that the bicarbonate complex formed by
      passing CO2 over the particles was accommodated on at least three distinct
      binding sites. At the lowest Al concentrations bicarbonate was bound to
      individual sites with primarily Fe or Al character. At the highest concentrations
      of Al (>20 mol%) bicarbonate bound to discrete AlOOH phases became apparent.
      Results also suggested that the amount of CO2 adsorption for a given particle
      mass increased as the Al concentration was increased from 0 to 30%. This increase
      was likely due in large part to differences in the morphology of the particle
      aggregates that formed in the dry state, which would be expected to affect the
      amount of surface that was available to adsorb CO2.

PMID- 23561822
TI  - Crystallinity-dependent substitutional nitrogen doping in ZnO and its improved
      visible light photocatalytic activity.
AB  - Increasing visible light absorption of wide-bandgap photocatalysts (for example,
      ZnO and TiO2) plays a pivotal role in improving their photocatalytic activity. In
      this work, we show that substitutional nitrogen doping can be realized in semi
      crystalline zinc oxide (ZnO) nanoparticles but fails for highly crystalline ZnO
      by heating the ZnO at a temperature of 400 degrees C in gaseous ammonia
      atmosphere. The results suggest that substitutional nitrogen for lattice oxygen
      is strongly dependent on the crystallinity of ZnO. The nitrogen doped ZnO
      obtained shows an improved visible light photocatalytic activity in the
      degradation of organic dyes due to its increased visible light absorption. The
      origin of the increased visible light absorption is theoretically attributed to
      the formed N 2p localized states in the bandgap.

PMID- 23561823
TI  - Ultra-rapid screening for substance-use disorders: the Alcohol, Smoking and
      Substance Involvement Screening Test (ASSIST-Lite).
AB  - BACKGROUND: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST
      3.0; index test) is a structured interview for alcohol, tobacco, cannabis,
      stimulants, sedatives and opioid use disorders in general medical settings.
      Perceived administration time deters routine use. This study releases a short
      form: the ASSIST-Lite. METHODS: Diagnostic accuracy study among 2082 adults
      recruited from general medical (70%) and specialist mental health/addiction
      treatment services (22%). Current DSM-IV substance dependence (MINI International
      Neuropsychiatric Interview) and moderate-severe tobacco dependence (Fagerstrom
      Nicotine Dependence Test) were reference standards. Exploratory factor and item
      response theory models re-calibrated ordinal test items. Items for the ASSIST
      Lite were selected by diagnostic accuracy evaluation (area under the receiver
      operating characteristic [AUC] curve [<=0.7]), sensitivity, specificity, positive
      and negative predictive values [PVP, NVP], kappa, likelihood ratios [LR+, LR-],
      and clinical utility index [CU+, CU-]). RESULTS: For each substance an item pair
      was selected (AUC [0.8-1.0], sensitivity [0.8-1.0], specificity [0.7-0.8], PVP
      [0.8-1.0], NVP [0.7-1.0], kappa [0.5-0.9], LR+ [2.5-5.9], LR- [0.0-0.2], CU+ [0.7
      0.9], and CU- [0.5-0.8]). Gender, age and recruitment setting (specialist mental
      health versus general medical) did not moderate accuracy, with the exception of
      opioids (AUC <0.7, participants >=59 years). Male opioid users had more severe
      substance involvement scores that females (differential item functioning
      analysis, P=0.00). There was no evidence of differential accuracy between
      countries (AUC range, 0.8-1.0). CONCLUSION: The ASSIST-Lite is an ultra-rapid
      screener which has been optimised for general medical settings. Optionally, a
      criterion question can be added to capture hazardous drinking, and to capture use
      of another type of mood-altering substance.

PMID- 23561824
TI  - Force enhancement and force depression in a modified muscle model used for muscle
      activation prediction.
AB  - This article introduces history-dependent effects in a skeletal muscle model
      applied to dynamic simulations of musculoskeletal system motion. Force depression
      and force enhancement induced by active muscle shortening and lengthening,
      respectively, represent muscle history effects. A muscle model depending on the
      preceding contractile events together with the current parameters was developed
      for OpenSim software, and applied in simulations of standing heel-raise and squat
      movements. Muscle activations were computed using joint kinematics and ground
      reaction forces recorded from the motion capture of seven individuals. In the
      muscle-actuated simulations, a modification was applied to the computed
      activation, and was compared to the measured electromyography data. For the
      studied movements, the history gives a small but visible effect to the muscular
      force trace, but some parameter values must be identified before the exact
      magnitude can be analysed. The muscle model modification improves the existing
      muscle models and gives a more accurate description of underlying forces and
      activations in musculoskeletal system movement simulations. 

PMID- 23561825
TI  - A study on body-weight perception, future intention and weight-management
      behaviour among normal-weight, overweight and obese women in India.
AB  - OBJECTIVE: We examined the socio-economic differential in the self-perception of
      body weight, future intention for weight management and actual weight-management
      behaviour among normal-weight, overweight and obese women in India. DESIGN: A
      population-based follow-up survey of ever-married women, systematically selected
      from the second round of the National Family Health Survey (NFHS-2, 1998-99)
      samples, who were re-interviewed after four years in 2003. SETTING: Information
      on women's perception about their own weight, intention of weight management and
      actual weight-management behaviour were collected through personal interview.
      Anthropometric measurements were obtained from women to compute their current
      BMI. SUBJECTS: Three hundred and twenty-five ever-married women aged 20-54 years
      residing in the national capital territory of Delhi in India. RESULTS:
      Discrepancy between self-perceived body weight and women's actual body weight was
      reported. One-quarter of overweight women and one in ten obese women perceived
      themselves as normal weight. Although a majority of overweight and obese women
      wanted to reduce their weight, a significant proportion of overweight (one in
      four) and 4 % of obese women also wanted to maintain their weight as it is. Only
      one in three overweight and one in four obese women were performing any physical
      activity to reduce their weight. CONCLUSIONS: These findings are important for
      public health interventions in obesity care. Implementation of health promotion
      and health education in the community should use effective school education and
      mass-media programmes to raise awareness of appropriate body weight to combat the
      growing level of obesity among Indian women.

PMID- 23561828
TI  - [The actual place of molecular analysis for donors and recipients in red blood
      cell immuno-hematology].
AB  - Molecular testing in red blood cell immuno-haematology is used extensively since
      the last 5 past years because of the technical developments and the possibility
      to use commercial kits. But these analyses have a high cost and rely on dedicated
      laboratories. Therefore, serology remains a reference technique for many
      laboratories in France, and in the world. Molecular analyses are used to resolve
      problems that cannot be resolved by serology. In this review, we will detail the
      main indications of molecular analysis, in donors and recipients, taking into
      account the technical tools that we can use, and the knowledge that we have about
      blood groups and their different variants. In this context, we have to remember
      that a molecular analysis has to be performed only if there is a benefice for the
      patient in the transfusion or the obstetrical setting.

PMID- 23561829
TI  - 'My mother...my sisters... and my friends': sources of maternal support in the
      perinatal period in urban India.
AB  - OBJECTIVE: to explore the wide-ranging sources of support that the maternal
      infant dyad need or expect throughout the perinatal period in urban India.
      DESIGN: qualitative interviews and ethnographic approach. SETTING: homes and
      community settings in greater metropolitan Bangalore, South India. PARTICIPANTS:
      using in-depth interviews of 36 mothers from different socio-cultural and socio
      economic backgrounds who had given birth within the past two years in a tertiary
      hospital, we explored the nature of support, advice and emotional sustenance
      through pregnancy, childbirth and the early child rearing period available to
      these women. FINDINGS: the overwhelming importance of women's own mothers in
      practical and emotional terms, the connectedness to 'native' place or 'ooru', the
      role of the diverse, extensive female network and the more contingent role of the
      husband emerged as major themes. The family was a major source of support as well
      as distress. While the support from their own mother was a constant, women used
      various forms of support throughout the perinatal continuum. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: we call for a more nuanced understanding of what women
      in urban India expect and need in terms of support throughout the perinatal
      period. Clinicians and policy makers need to understand the various players,
      their different roles at critical times through the perinatal continuum and be
      able to identify those who are vulnerable and in need of enhanced support.
      Although the health sector is not a strong player in the socio-cultural milieu in
      the perinatal period, their role as facilitators of this support is crucial.

PMID- 23561830
TI  - Uncorrected traumatic coagulopathy is associated with severe brain swelling
      during decompressive surgery to evacuate a supratentorial intradural mass lesion
      in patients with traumatic brain injury.
AB  - OBJECTIVE: This study investigated the relationship between traumatic
      coagulopathy and severe brain swelling (SBS) during decompressive surgery to
      evacuate a supratentorial intradural mass lesion in patients with traumatic brain
      injury (TBI). METHODS: A retrospective study was conducted in 96 patients who
      consecutively suffered from isolated TBI and underwent decompressive surgery to
      evacuate a supratentorial traumatic mass lesion by unilateral craniotomy. Their
      medical history, radiographic information, and surgical notes were reviewed. The
      relationship between traumatic coagulopathy and intraoperative SBS was evaluated.
      RESULTS: Fifty-six patients presented with traumatic coagulopathy according to
      their preoperative coagulation panels. Thirty of them had the disorder corrected
      before surgery while the remaining patients did not. Twenty-four patients
      developed intraoperative SBS, and 22 (91.7%) of them were related to new or
      progressive formation of distal intracranial lesions during the surgery. Patients
      with uncorrected coagulopathy demonstrated a significantly higher risk of
      intraoperative SBS than those with corrected and no coagulopathy (61.5% vs 11.4%,
      P < 0.001). There was no significant difference in the incidence of
      intraoperative SBS between patients with corrected and no coagulopathy (13.3%
      versus 10.0%, P > 0.05). Multivariate logistic regression analysis showed that
      uncorrected coagulopathy was an independent risk factor and related to an 11.5
      fold increased risk of intraoperative SBS. CONCLUSIONS: Intraoperative SBS is not
      a rare event during decompressive surgery to evacuate a supratentorial intradural
      mass lesion in patients with TBI. Such surgery should be cautiously considered
      and performed given the existence of uncorrected traumatic coagulopathy, which is
      associated with an increased risk of intraoperative SBS.

PMID- 23561827
TI  - Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves
      sensorimotor behavioral performance in neonatal rats exposed to systemic
      lipopolysaccharide.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is induced in inflammatory cells in response
      to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role in
      the inflammatory process. The objective of the current study was to examine
      whether celecoxib, a selective COX-2 inhibitor, could ameliorate
      lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal
      dysfunction and sensorimotor behavioral impairments. METHODS: Intraperitoneal
      (i.p.) injection of LPS (2 mg/kg) was performed in rat pups on postnatal Day 5
      (P5), and celecoxib (20 mg/kg) or vehicle was administered (i.p.) five minutes
      after LPS injection. Sensorimotor behavioral tests were carried out 24 h after
      LPS exposure, and brain injury was examined on P6. RESULTS: Our results showed
      that LPS exposure resulted in impairment in sensorimotor behavioral performance
      and injury to brain dopaminergic neurons, as indicated by loss of tyrosine
      hydroxylase (TH) immunoreactivity, as well as decreases in mitochondria activity
      in the rat brain. LPS exposure also led to increases in the expression of alpha
      synuclein and dopamine transporter proteins and enhanced [3H]dopamine uptake.
      Treatment with celecoxib significantly reduced LPS-induced sensorimotor
      behavioral disturbances and dopaminergic neuronal dysfunction. Celecoxib
      administration significantly attenuated LPS-induced increases in the numbers of
      activated microglia and astrocytes and in the concentration of IL-1beta in the
      neonatal rat brain. The protective effect of celecoxib was also associated with
      an attenuation of LPS-induced COX-2+ cells, which were double labeled with TH +
      (dopaminergic neuron) or glial fibrillary acidic protein (GFAP) + (astrocyte)
      cells. CONCLUSION: Systemic LPS administration induced brain inflammatory
      responses in neonatal rats; these inflammatory responses included induction of
      COX-2 expression in TH neurons and astrocytes. Application of the COX-2 inhibitor
      celecoxib after LPS treatment attenuated the inflammatory response and improved
      LPS-induced impairment, both biochemically and behaviorally.

PMID- 23561831
TI  - Simvastatin induces apoptosis and disruption of the actin cytoskeleton in human
      dental pulp cells and periodontal ligament fibroblasts.
AB  - OBJECTIVE: Simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase, and widely used as cholesterol-lowering agent, has been
      suggested for its beneficial effects on alveolar bone formation, regeneration of
      dental pulp tissue and periodontal ligament. High doses of simvastatin appear to
      induce apoptosis in several cell types, but little is known about its possible
      effect on tooth-associated cells. Therefore, the effects of simvastatin were
      studied on apoptosis and cell morphology of human dental pulp cells (HDPCs) and
      periodontal ligament fibroblasts (HPLFs). METHODS: HDPCs/HPLFs obtained from 4
      patients were cultured with or without various concentrations of simvastatin
      (0.1, 1, and 10MUM) for 24, 48, and 72h. The 3-(4,5-dimethyl-thiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay was performed to evaluate cell viability.
      The levels of apoptosis of HDPCs and HPLFs were measured by flow cytometry after
      Annexin V/propidium iodide double staining. Phalloidin-FITC and 4',6-diamidino-2
      phenylindole dihydrochloride (DAPI) staining was used to examine differences in
      the actin cytoskeleton and nuclear morphology, respectively. RESULTS: The
      viability of HDPCs and HPLFs was significantly reduced after simvastatin
      treatment in a dose- and time-dependent manner (p<0.05). The apoptosis of HDPCs
      and HPLFs was significantly increased in 10MUM simvastatin-treated cells
      (p<0.05). The effect on apoptosis was comparable for HDPCs and HPLFs. Nuclear
      staining showed typical apoptotic nuclear condensation and fragmentation in
      simvastatin-treated HDPCs/HPLFs. A dose- and time-dependent simvastatin-induced
      disruption of the actin cytoskeleton was observed in both cell types. CONCLUSION:
      Our data demonstrated that simvastatin decreases the viability of HDPCs and
      HPLFs, probably by inducing apoptosis.

PMID- 23561832
TI  - A case of constrictive pericarditis and thoracic aortic aneurysm: a hybrid
      therapeutic approach.
AB  - The authors describe the case of a 59-year-old man, a former smoker, with
      hypertension, chronic renal failure undergoing hemodialysis, and a history of
      stent grafting for repair of an abdominal aortic aneurysm and miliary
      tuberculosis, who was diagnosed with constrictive pericarditis and a thoracic
      aortic aneurysm. In a patient with such a complex medical history, there were
      several etiologies to consider. The treatment consisted of pericardiectomy and a
      hybrid technique of supra-aortic debranching and subsequent endovascular stent
      graft repair. 

PMID- 23561834
TI  - Multiple sclerosis patients and clinical care in Taiwan.
AB  - OBJECTIVES: Multiple sclerosis (MS) displays marked clinical heterogeneity.
      However, what healthcare services MS patients would use is not clear. The purpose
      of this retrospective study is to understand how patients diagnosed with MS used
      clinical services over a 10-year period in Taiwan. METHODS: Data from 123
      consecutive patients meeting Poser or McDonald criteria for a diagnosis of MS
      treated at Chang Gung Memorial Hospital, Linkou, were reviewed. Data were
      analyzed in a descriptive manner and non-categorical variables were compared
      using the Mann-Whitney U-test or student's t-test. Associated factors were
      analyzed with logistic regression and/or a multiple regression model. RESULTS:
      The average age at the first signs of MS was 35.5+/-13.1 years, and the average
      duration between the first disease episode and confirmed diagnosis was 1.6+/-3.3
      years. We found that 51.6% (33/64) of patients with optic pathway symptoms
      visited a medical center as their first choice when seeking medical care,
      followed by 48.4% (31/64) of patients with brainstem/cerebellum symptoms. There
      was no significant difference in time lag between the first attack and the
      confirmed diagnosis. DISCUSSION: These observations may be helpful in raising
      further awareness of the disease among general practitioners and neurologists.

PMID- 23561835
TI  - MALT-STAFF 2012 symposium overview.

PMID- 23561836
TI  - Consideration of QRS complex in addition to ST segment abnormalities in the
      estimation of the 'risk region' during acute inferior myocardial infarction.
AB  - BACKGROUND: The myocardial area at risk (MaR) has been estimated in patients with
      acute myocardial infarction (AMI) by using ST segment based ECG methods. However,
      as the process from ischemia to infarction progresses, the ST segment deviation
      is typically replaced by QRS abnormalities, causing a falsely low estimation of
      the total MaR if determined by using ST segment based methods. A previous study
      showed the value of the consideration of the abnormalities in the QRS complex, in
      addition to those in the ST segment estimating the total MaR for patients with
      anterior AMI. The purpose of this study was to investigate the same method for
      patients with inferior AMI. METHODS: Thirty-two patients with acute inferior ST
      elevation myocardial infarction received (99m)Tc-Sestamibi before percutaneous
      coronary intervention. SPECT was performed within 2 hours after treatment and was
      used as a gold standard for the estimation of the total MaR. The ECG recorded at
      admission in the hospital was used for the ECG estimates of the total MaR. This
      included a ST segment estimation of the ischemic component of the total MaR
      (Aldrich score) and an estimation of the infarcted component of the total MaR in
      the acute phase of AMI by QRS abnormalities (Selvester score). These scores were
      added for the combined ECG score. RESULTS: The ischemic component of the total
      MaR estimated by the Aldrich score alone no statistically significant correlation
      with SPECT (r=0.17, p=0.36). The infarcted component of the total MaR estimated
      by the Selvester score showed a significant correlation with SPECT (r=0.55,
      p=0.001). When the Aldrich and Selvester scores were combined, the correlation
      with SPECT improved (r=0.58, p<0.001). Both the Aldrich and Selvester score alone
      underestimated the mean MaR measured by SPECT (respectively p=0.007 and
      p<0.0001). There was no statistically significant difference between the mean MaR
      estimated by the sum of Aldrich and Selvester and the MaR measured by SPECT
      (p=0.636). CONCLUSION: The estimation of the total MaR was more accurate by
      taking both ST deviation and QRS abnormalities in account than by using either
      method alone. A new ECG method to determine the total MaR during acute coronary
      occlusion should consider both its ischemic and infarcted components.

PMID- 23561837
TI  - The predictive value of an ECG-estimated Acute Ischemia Index for prognosis of
      myocardial salvage and infarct healing 3months following inferior ST-elevated
      myocardial infarction.
AB  - BACKGROUND AND PURPOSE: Identification of prognostic markers can be used to
      stratify patients in the acute phase of ST-elevated myocardial infarction (STEMI)
      according to their potential to retain viable myocardium after reperfusion. The
      percentage of the myocardial area at risk (MaR) that is ischemic at admission,
      defined as the Acute Ischemia Index, is potentially salvageable. The percentage
      of the MaR viable at 3months post-reperfusion, by salvage and healing, was
      defined as the Chronic Salvage Index. A positive relationship between the Acute
      Ischemia Index and the Chronic Salvage Index was hypothesized. METHODS: Both
      indices were assessed by using the ECG indices Aldrich ST and Selvester QRS
      scores estimating the ischemic and infarcted myocardium. The study population
      comprised inferior STEMI patients. (N=59). RESULTS: A correlation of 0.253
      (P=0.053) was found. CONCLUSIONS: These results are relevant and suggest evidence
      of a trend in the association between these indices.

PMID- 23561838
TI  - Monsef Benkirane awarded 2013 Ming K. Jeang Foundation Retrovirology Prize:
      landmark HIV-1 research honoured.

PMID- 23561839
TI  - Occult pulmonary embolism in intensive care unit patients undergoing chest
      computed tomography scan: incidence and effect on outcomes.
AB  - OBJECTIVE: To determine the incidence of occult pulmonary embolism (PE) and the
      associated morbidity in an intensive care unit (ICU). DESIGN: Retrospective
      study. SETTING: Fifteen-bed ICU of a university hospital. PARTICIPANTS: Two
      hundred patients who underwent chest computed tomography (CT) scans with
      administration of contrast. INTERVENTIONS: The patients were classified into 3
      groups: (1) Occult PE if the chest CT scan was not taken, specifically for
      elucidating the diagnosis of PE, but it confirmed this diagnosis; (2) non-occult
      PE if the chest CT scan was taken to elucidate a suspected diagnosis of PE and
      confirmed this diagnosis; and (3) the chest CT scan did not confirm this
      diagnosis. The analysis was conducted to identify the effect of a diagnosis of
      occult PE on the outcomes of patients. MEASUREMENTS AND MAIN RESULTS: Among the
      200 patients who underwent chest CT scan, 27 (13%) patients had PE, in whom 18
      (9%) were classified as occult PE and 9 (4.5%) as non-occult PE. The duration of
      ICU stay was increased in patients with PE, as compared with the controls (23 [18
      48] days v 17 [10-20] days v 14 [7-29] days; p = 0.02 for occult PE, non-occult
      PE, and controls, respectively). No difference was observed in mortality rate
      among the 3 groups. CONCLUSION: Occult PE was found in 9% of the cohort. This
      emphasized the need for developing diagnostic strategies in high-risk patients.
      Future studies should aim at assessing interventions for preventing this event.

PMID- 23561840
TI  - High-dose propofol reduces S-100beta protein and neuron-specific enolase levels
      in patients undergoing cardiac surgery.
AB  - OBJECTIVES: In a variety of experimental models, propofol has been shown to
      protect the brain. It was hypothesized that a clinically achievable high dose of
      propofol would induce cerebral protective effects in patients undergoing cardiac
      surgery with cardiopulmonary bypass (CPB). The authors investigated the effects
      of different target plasma concentrations of propofol on cerebral injury by
      measuring serum S-100beta protein and neuron-specific enolase (NSE) levels in
      patients undergoing single-valve replacement with CPB. DESIGN: A prospective,
      randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-two
      patients undergoing single-valve replacement with CPB. INTERVENTIONS: Patients
      were randomly divided into 3 groups (n = 14 each). Each group received a target
      controlled infusion of propofol with plasma concentrations of 1.8 MUg/mL (low
      dose, Group-L), 2.4 MUg/mL (medium dose, Group-M), or 3.2 MUg/mL (high dose,
      Group-H). The propofol target concentrations were unchanged throughout the
      surgery. MEASUREMENTS AND MAIN RESULTS: In all 3 groups of patients, at all time
      points after CPB, the plasma S-100beta protein and NSE levels, which served as
      biochemical markers of brain damage, were significantly higher than the
      preoperative levels (p<0.05). Group-H showed significant decreases in S-100beta
      protein and NSE compared with Group-L (p< 0.05). CONCLUSION: In the range of
      commonly used clinical concentrations, administration of a high dose of propofol
      during CPB attenuated the biochemical markers of brain damage as compared with
      low-dose propofol anesthesia.

PMID- 23561841
TI  - Silver nanoparticle toxicity in sea urchin Paracentrotus lividus.
AB  - Silver nanoparticles (AgNPS) are an important model system for studying potential
      environmental risks posed by the use of nanomaterials. So far there is no
      consensus as to whether toxicity is due to AgNPs themselves or Ag(+) ions
      leaching from their surfaces. In sea urchin Paracentrotus lividus, AgNPs cause
      dose dependent developmental defects such as delayed development, bodily
      asymmetry and shortened or irregular arms, as well as behavioural changes,
      particularly in swimming patterns, at concentration ~0.3 mg/L AgNPs. It has been
      observed that AgNPs are more toxic than their equivalent Ag(+) ion dose.

PMID- 23561842
TI  - Efficacy of a store-based environmental change intervention compared with a
      delayed treatment control condition on store customers' intake of fruits and
      vegetables.
AB  - OBJECTIVE: The present store-based intervention was designed to promote sales of
      fruits and vegetables (F&V) to increase intake among store customers-
      specifically customers of tiendas, small-to-medium-sized Latino food stores.
      DESIGN: Four tiendas were randomized to a 2-month environmental change
      intervention or a delayed treatment control condition. Employees and managers
      were trained to promote F&V sales, including how to implement a food marketing
      campaign and installing store equipment to promote fresh fruits and vegetables.
      The primary outcome was self-reported daily intake of F&V among a convenience
      sample of customers (at least forty per store) collected at baseline prior to
      randomization and then 4 months later. In addition, changes in availability of
      F&V in the tiendas, using unobtrusive observational methods, provided evidence of
      intervention fidelity. SETTING: Tiendas in central North Carolina. SUBJECTS:
      Participants included 179 customers who were recent immigrants from Mexico and
      Central America. RESULTS: A group-by-time interaction approached significance on
      daily servings of F&V; intervention customers reported an increase in F&V intake
      over time and as a function of the intervention (P < or = 0.06). Unexpectedly,
      self-efficacy for consuming more fruits (P < or = 0.01) and more vegetables (P <
      or = 0.06) decreased. In our store-level analyses, a group-by-time interaction
      was observed for availability of fresh and canned vegetables; the intervention
      increased availability of vegetables but not fruit. CONCLUSIONS: Environmental
      change strategies to promote healthy eating are needed given the rates of obesity
      and diabetes in the Latino population. A store-based intervention was moderately
      effective at increasing customers' reported F&V intake. Such strategies can have
      a public health impact on underserved populations.

PMID- 23561843
TI  - A mechanism for controlled access to GWAS data: experience of the GAIN Data
      Access Committee.
AB  - The Genetic Association Information Network (GAIN) Data Access Committee was
      established in June 2007 to provide prompt and fair access to data from six
      genome-wide association studies through the database of Genotypes and Phenotypes
      (dbGaP). Of 945 project requests received through 2011, 749 (79%) have been
      approved; median receipt-to-approval time decreased from 14 days in 2007 to 8
      days in 2011. Over half (54%) of the proposed research uses were for GAIN
      specific phenotypes; other uses were for method development (26%) and adding
      controls to other studies (17%). Eight data-management incidents, defined as
      compromises of any of the data-use conditions, occurred among nine approved
      users; most were procedural violations, and none violated participant
      confidentiality. Over 5 years of experience with GAIN data access has
      demonstrated substantial use of GAIN data by investigators from academic,
      nonprofit, and for-profit institutions with relatively few and contained policy
      violations. The availability of GAIN data has allowed for advances in both the
      understanding of the genetic underpinnings of mental-health disorders, diabetes,
      and psoriasis and the development and refinement of statistical methods for
      identifying genetic and environmental factors related to complex common diseases.

PMID- 23561844
TI  - GIGI: an approach to effective imputation of dense genotypes on large pedigrees.
AB  - Recent emergence of the common-disease-rare-variant hypothesis has renewed
      interest in the use of large pedigrees for identifying rare causal variants.
      Genotyping with modern sequencing platforms is increasingly common in the search
      for such variants but remains expensive and often is limited to only a few
      subjects per pedigree. In population-based samples, genotype imputation is widely
      used so that additional genotyping is not needed. We now introduce an analogous
      approach that enables computationally efficient imputation in large pedigrees.
      Our approach samples inheritance vectors (IVs) from a Markov Chain Monte Carlo
      sampler by conditioning on genotypes from a sparse set of framework markers.
      Missing genotypes are probabilistically inferred from these IVs along with
      observed dense genotypes that are available on a subset of subjects. We
      implemented our approach in the Genotype Imputation Given Inheritance (GIGI)
      program and evaluated the approach on both simulated and real large pedigrees.
      With a real pedigree, we also compared imputed results obtained from this
      approach with those from the population-based imputation program BEAGLE. We
      demonstrated that our pedigree-based approach imputes many alleles with high
      accuracy. It is much more accurate for calling rare alleles than is population
      based imputation and does not require an outside reference sample. We also
      evaluated the effect of varying other parameters, including the marker type and
      density of the framework panel, threshold for calling genotypes, and population
      allele frequencies. By leveraging information from existing genotypes already
      assayed on large pedigrees, our approach can facilitate cost-effective use of
      sequence data in the pursuit of rare causal variants.

PMID- 23561845
TI  - Improving the accuracy and efficiency of partitioning heritability into the
      contributions of genomic regions.
AB  - Quantifying heritability, the amount of genetic contribution in a complex trait,
      has been of fundamental interest to geneticists for decades. Recently,
      partitioning the heritability accounted for by common variants into the
      contributions of genomic regions has received a lot of attention given its
      important applications for understanding the genetic architecture of complex
      traits. Current methods partition the total heritability by jointly estimating
      the contributions of all regions. However, these methods are computationally
      intractable and can be inaccurate when the number of regions is large. In this
      paper, we present an alternative approach that partitions the total heritability
      into the contributions of an arbitrary number of regions. We demonstrate by using
      simulations that our approach is more accurate and computationally efficient than
      current approaches. Using a data set from a genome-wide association study on
      human height, we demonstrate the utility of our method by estimating the
      heritability contributions of chromosomes and subchromosomal regions.

PMID- 23561846
TI  - Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause
      autosomal-recessive intellectual disability.
AB  - PGAP2 encodes a protein involved in remodeling the glycosylphosphatidylinositol
      (GPI) anchor in the Golgi apparatus. After synthesis in the endoplasmic reticulum
      (ER), GPI anchors are transferred to the proteins and are remodeled while
      transported through the Golgi to the cell membrane. Germline mutations in six
      genes (PIGA, PIGL, PIGM, PIGV, PIGN, and PIGO) in the ER-located part of the GPI
      anchor-biosynthesis pathway have been reported, and all are associated with
      phenotypes extending from malformation and lethality to severe intellectual
      disability, epilepsy, minor dysmorphisms, and elevated alkaline phosphatase
      (ALP). We performed autozygosity mapping and ultra-deep sequencing followed by
      stringent filtering and identified two homozygous PGAP2 alterations, p.Tyr99Cys
      and p.Arg177Pro, in seven offspring with nonspecific autosomal-recessive
      intellectual disability from two consanguineous families. Rescue experiments with
      the altered proteins in PGAP2-deficient Chinese hamster ovary cell lines showed
      less expression of cell-surface GPI-anchored proteins DAF and CD59 than of the
      wild-type protein, substantiating the pathogenicity of the identified
      alterations. Furthermore, we observed a full rescue when we used strong promoters
      before the mutant cDNAs, suggesting a hypomorphic effect of the mutations. We
      report on alterations in the Golgi-located part of the GPI-anchor-biosynthesis
      pathway and extend the phenotypic spectrum of the GPI-anchor deficiencies to
      isolated intellectual disability with elevated ALP. GPI-anchor deficiencies can
      be interpreted within the concept of a disease family, and we propose that the
      severity of the phenotype is dependent on the location of the altered protein in
      the biosynthesis chain.

PMID- 23561847
TI  - PGAP2 mutations, affecting the GPI-anchor-synthesis pathway, cause
      hyperphosphatasia with mental retardation syndrome.
AB  - Recently, mutations in genes involved in the biosynthesis of the
      glycosylphosphatidylinositol (GPI) anchor have been identified in a new subclass
      of congenital disorders of glycosylation (CDGs) with a distinct spectrum of
      clinical features. To date, mutations have been identified in six genes (PIGA,
      PIGL, PIGM, PIGN, PIGO, and PIGV) encoding proteins in the GPI-anchor-synthesis
      pathway in individuals with severe neurological features, including seizures,
      muscular hypotonia, and intellectual disability. We developed a diagnostic gene
      panel for targeting all known genes encoding proteins in the GPI-anchor-synthesis
      pathway to screen individuals matching these features, and we detected three
      missense mutations in PGAP2, c.46C>T, c.380T>C, and c.479C>T, in two unrelated
      individuals with hyperphosphatasia with mental retardation syndrome (HPMRS). The
      mutations cosegregated in the investigated families. PGAP2 is involved in fatty
      acid GPI-anchor remodeling, which occurs in the Golgi apparatus and is required
      for stable association between GPI-anchored proteins and the cell-surface
      membrane rafts. Transfection of the altered protein constructs, p.Arg16Trp
      (NP_001243169.1), p.Leu127Ser, and p.Thr160Ile, into PGAP2-null cells showed only
      partial restoration of GPI-anchored marker proteins, CD55 and CD59, on the cell
      surface. In this work, we show that an impairment of GPI-anchor remodeling also
      causes HPMRS and conclude that targeted sequencing of the genes encoding proteins
      in the GPI-anchor-synthesis pathway is an effective diagnostic approach for this
      subclass of CDGs.

PMID- 23561848
TI  - Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes
      combined D-2- and L-2-hydroxyglutaric aciduria.
AB  - The Krebs cycle is of fundamental importance for the generation of the energetic
      and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of
      metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical
      pathway and are found elevated not only in several cancers, but also in different
      variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we
      showed that cancer-associated IDH2 germline mutations cause one variant of 2
      hydroxyglutaric aciduria. Complementary to these findings, we now report
      recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of
      12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired
      mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments
      and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest
      that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as
      a cause of combined D-2- and L-2-hydroxyglutaric aciduria.

PMID- 23561849
TI  - Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder
      of glycosylation.
AB  - Biochemical analysis and whole-exome sequencing identified mutations in the Golgi
      localized UDP-galactose transporter SLC35A2 that define an undiagnosed X-linked
      congenital disorder of glycosylation (CDG) in three unrelated families. Each
      mutation reduced UDP-galactose transport, leading to galactose-deficient
      glycoproteins. Two affected males were somatic mosaics, suggesting that a wild
      type SLC35A2 allele may be required for survival. In infancy, the commonly used
      biomarker transferrin showed abnormal glycosylation, but its appearance became
      normal later in childhood, without any corresponding clinical improvement. This
      may indicate selection against cells carrying the mutant allele. To detect other
      individuals with such mutations, we suggest transferrin testing in infancy. Here,
      we report somatic mosaicism in CDG, and our work stresses the importance of
      combining both genetic and biochemical diagnoses.

PMID- 23561850
TI  - Frameshift-derived neoantigens constitute immunotherapeutic targets for patients
      with microsatellite-instable haematological malignancies: frameshift peptides for
      treating MSI+ blood cancers.
AB  - PURPOSE: Microsatellite instability (MSI) resulting from loss of functional DNA
      mismatch repair was recently found in various haematological disorders. In coding
      sequences, MSI leads to frameshift mutations (FSMs) and the production of C
      terminally altered proteins which are foreign to the immune system. Here, we
      wondered whether these frame-shifted peptide (FSP) sequences represent tumour
      specific antigens also for MSI(+) leukaemia and lymphomas (L/L). MATERIAL AND
      METHODS: A total of 33 coding region microsatellites were examined in MSI(+) L/L
      cell lines for the presence of FSMs. Thereafter, recognition of MSI(+) cells by
      established FSP-specific CD8(+) T cell lines was quantified using interferon
      (IFN)-gamma enzyme-linked immunospot (ELISpot) assays. In each experiment, MSI(+)
      L/L cell lines and T2 targets exogenously loaded with the cognate peptide
      (=internal control) were employed. Supplementary, lytic activity towards tumour
      cells was analysed by standard chromium release assay ((51)Cr). RESULTS:
      Mutational profiling of 33 coding microsatellite loci in nine MSI(+) L/L cell
      lines revealed instability in at least nine microsatellites. In each cell line, a
      distinct mutational profile was observed. Only three of the 33 loci were stable.
      FSP-specific and human leukocyte antigen-A2 (HLA-A2)-restricted T cells
      specifically recognised MSI(+) L/L cells endogenously expressing TGFbetaRII(-1),
      Caspase 5 (-1) and MSH3 (-1) in ELISpot assays. Moreover, specific killing of
      Caspase 5 (-1) and MSH3 (-1) expressing L/L cell lines was achieved in functional
      cytotoxicity assays. CONCLUSION: Data presented here expand the importance of
      FSPs as shared and general tumour-specific antigens. Consequently, they open new
      avenues for specific immunotherapies not only for solid but also for MSI(+)
      haematological malignancies.

PMID- 23561851
TI  - Adrenocortical carcinoma: a population-based study on incidence and survival in
      the Netherlands since 1993.
AB  - BACKGROUND: The reported annual incidence of adrenocortical carcinoma (ACC) is
      0.5-2.0 cases per million individuals. Updated population-based studies on
      incidence are lacking. The aim of this nationwide survey was to describe the
      incidence and survival rates of ACC in the Netherlands. Secondary objectives were
      to evaluate changes in both survival rates and the number of patients undergoing
      surgery. METHODS: All ACC patients registered in the Netherlands Cancer Registry
      (NCR) between 1993 and 2010 were included. Data on demographics, stage of
      disease, primary treatment modality and survival were evaluated. RESULTS:
      Included were 359 patients, 196 of whom were female (55%). Median age at
      diagnosis was 56 years (range 1-91). The 5-year age-standardised incidence rate
      decreased from 1.3 to 1.0 per one million person-years. Median survival for
      patients with stage I-II, stage III and stage IV disease was 159 months (95%
      confidence interval (CI) 93-225 months), 26 months (95% CI: 4-48 months) and 5
      months (95% CI: 2-7 months), respectively (P<0.001). Improvement in survival was
      not observed, as reflected by the lack of association between survival and time
      of diagnosis. The percentage of patients receiving treatment within 6 months
      after diagnosis increased significantly from 76% in 1993-1998 to 88% in 2005-2010
      (P=0.047), mainly due to an increase in surgery for stage III-IV patients.
      CONCLUSION: These nationwide data provide an up-to-date survey of the
      epidemiology of ACC in the Netherlands. A trend towards a decreasing overall
      incidence rate was observed. Survival rates did not change during this period
      despite an increased number of surgical procedures.

PMID- 23561852
TI  - The functional demand (FD) placed on the knee and hip of older adults during
      everyday activities.
AB  - Age-related decline in physical capacity and diminishing physiological reserves
      may increase the demand placed on lower extremity joints during everyday
      activities. This study aimed to characterize the FD at the knee and hip joints of
      older adults during various mobility activities. Eighty-four healthy participants
      (60-88 years) performed strength tests using a custom-built dynamometer.
      Biomechanical assessment of gait, chair rise (CR) and sit-down (CSt), stair
      ascent (SA) and descent (SD) was performed using an 8-camera VICON system (120Hz)
      and Kistler force plates. Comparisons between groups (60s, 70s and 80s) were made
      using ANOVA. The FD was defined as the muscle moment generated during a task,
      divided by the maximum isometric strength (expressed as a percentage). FD was
      higher in the 80s age group compared to those in the 60s. The demand on hip and
      knee extensors was normally higher than those of flexors across all the
      activities. The knee extensor demand during gait (101%), SA (103%) and SD (120%),
      and hip extensor demand during gait (127%) were high requiring moments in excess
      of the maximum isometric muscle strength available at these joints. FD during CR
      and CSt was comparatively lower with knee extensor demands of 73% and 69% and hip
      extensor demands of 88% and 51%, respectively. Gait, SA and SD placed high
      demands on the knee extensors while hip extensor demand was high for gait, CR,
      CSt and SA. The levels of demand leave little reserve capacity for the older
      adult to draw on in unexpected circumstances.

PMID- 23561853
TI  - Bovine viral diarrhea virus fetal persistent infection after immunization with a
      contaminated modified-live virus vaccine.
AB  - The objective was to determine whether a multivalent modified-live virus vaccine
      containing noncytopathic bovine viral diarrhea virus (BVDV) administered off
      label to pregnant cattle can result in persistently infected fetuses and to
      assess whether vaccinal strains can be shed to unvaccinated pregnant cattle
      commingling with vaccinates. Nineteen BVDV-naive pregnant heifers were randomly
      assigned to two groups: cattle vaccinated near Day 77 of gestation with modified
      live virus vaccine containing BVDV-1a (WRL strain), bovine herpes virus-1,
      parainfluenza 3, and bovine respiratory syncytial virus (Vx group; N = 10) or
      control unvaccinated cattle (N = 9). During the course of the study a voluntary
      stop-sale/recall was conducted by the manufacturer because of the presence of a
      BVDV contaminant in the vaccine. At Day 175 of gestation, fetuses were removed by
      Cesarean section and fetal tissues were submitted for virus isolation, and
      quantitative reverse transcription polymerase chain reaction using BVDV-1- and
      BVDV-2-specific probes. Nucleotide sequencing of viral RNA was performed for
      quantitative reverse transcription polymerase chain reaction-positive samples.
      Two vaccinated and two control heifers aborted their pregnancies, but their
      fetuses were unavailable for BVDV testing. Virus was isolated from all eight
      fetuses in the Vx group heifers and from 2 of 7 fetuses in the control
      unvaccinated heifers. Only BVDV-2 was detected in fetuses from the Vx group, and
      only BVDV-1 was detected in the two fetuses from the control group. Both BVDV-1
      and BVDV-2 were detected in the vaccine. In conclusion, vaccination of pregnant
      heifers with a contaminated modified-live BVDV vaccine resulted in development of
      BVDV-2 persistently infected fetuses in all tested vaccinated animals.
      Furthermore, BVDV was apparently shed to unvaccinated heifers causing fetal
      infections from which only BVDV-1 was detected.

PMID- 23561855
TI  - [Evaluation of postoperative pain and early functional results in the treatment
      of carpometacarpal joint arthritis. Comparative prospective study of
      trapeziectomy vs. MAIA((r)) prosthesis in 74 female patients].
AB  - Trapeziectomy has been the basis of basal thumb arthritis surgical treatment
      since the 1950s. This resection arthroplasty has been continuously refined (soft
      tissue interposition, ligament reconstruction, spacer implantation, etc.) without
      leading to a dramatic outcome improvement. Pain decrease is often satisfying in
      the long-term, but comfort during the early postoperative period may vary. Those
      disadvantages of trapeziectomy led to the emergence of total trapeziometacarpal
      prostheses in the 1970s, with a constant improvement of implant design. Few
      series have compared those two surgical techniques side by side, and prospective
      ones are even rarer. We compared total trapeziometacarpal prosthesis and
      trapeziectomy-interposition in the very short term in two similar groups of
      female patients, to determine whether prosthesis led to faster recovery or not.
      We compared a total trapeziometacarpal prosthesis (MAIA((r))) and trapeziectomy
      interposition in the immediate and short-term (6 months), for objective,
      subjective, functional criteria, as well as short-term comfort or discomfort. We
      prospectively followed two comparable cohorts of 47 and 27 female patients above
      50 years of age, treated for basal joint arthritis with a constrained
      trapeziometacarpal joint prosthesis or trapeziectomy-interposition, respectively,
      between April 2009 and February 2010. The patients were followed postoperatively
      for 6 months. Mobility, pain reduction, satisfaction, strength and functional
      scores were better in the prosthesis group. The pinch strength improved by 30%,
      the length of the thumb column was maintained, and better correction of the
      subluxation was obtained in this group. There were six cases of De Quervain's
      tenosynovitis and one case of loosening due to trauma. In the short-term, the
      MAIA((r)) trapeziometacarpal prosthesis gives better outcome than trapeziectomy
      with interposition. This has to be confirmed in the long-term and after revision
      surgery that will be likely to occur. CLINICAL RELEVANCE: Therapeuthic 3.

PMID- 23561854
TI  - Engineering the male-specificity of Fab against SDM antigen by chain shuffling.
AB  - High-titer serologically detected male (SDM) antibody fragments are essential for
      specific binding to the SDM antigen and promoting its application. The A8 clone
      previously obtained from an original phage antibody library was further affinity
      matured by light- and high-chain shuffling respectively, to generate the end
      product B9 clone. The binding capacity of B9 phage Fabs to male splenocytes
      doubled the value of its parental A8 clone (determined using ELISA). Based on
      immunofluorescent staining, B9-Fabs mainly bound to the surface antigen of male
      splenocytes and recognized testicular cells. The resulting B9-Fabs detected a
      single protein (approximately 40 kDa determined using Western blot analysis of
      male splenocytes and testis); its high SDM antigen binding ability might have
      been because of mutation sites and varied lengths of the amino acid sequences in
      the complementarity determining regions-3 of the kappa and Fd chains. The new
      recombinant clones of Fab that were phage-enhanced using chain shuffling were
      candidate molecules for investigating molecular mechanisms of SDM antigens
      specific binding and applications.

PMID- 23561857
TI  - The atmospheric degradation reaction of dehydroabietic acid (DHAA) initiated by
      OH radicals and O3.
AB  - Dehydroabietic acid (DHAA) is the major marker compound emitted from the burning
      of conifer. In this paper, the atmospheric mechanism of DHAA initiated by OH
      radicals and O3 was studied at the MPWB1K/6-31+G(d,p)//MPWB1K/6-311+G(3df,2p)
      level. For OH radicals, two types of reactions including OH addition and hydrogen
      abstraction were investigated. The cycloaddition reactions of O3 were considered.
      The rate constants over the temperature range of 200-400 K were calculated with
      the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. At 298 K and under the pressure
      of 760 Torr, the whole rate constants are 0.89*10(-11) cm(3) molecule(-1) s(-1)
      and 2.29*10(-20) cm(3) molecule(-1) s(-1) for DHAA+OH and DHAA+O3, respectively.
      This study can be regarded as an attempt to investigate the OH-initiated and O3
      initiated photochemical reaction mechanisms of DHAA in the atmosphere.

PMID- 23561856
TI  - The effect of soil bioaugmentation with strains of Pseudomonas on Cd, Zn and Cu
      uptake by Sinapis alba L.
AB  - The aim of this study was to assess the ability of selected metal resistant
      strains of the Pseudomonas genus to increase Zn, Cd and Cu uptake by the
      metalophyte Sinapis alba L. under laboratory conditions. Moreover, the mechanisms
      of the plant growth promotion in the tested strains and their impact on the
      shoots and roots of white mustard biomass were examined. Soil inoculation with
      the tested strains resulted in higher concentrations of Zn, Cd and Cu in the
      shoots and roots of the plants in comparison with those grown in non-inoculated
      soil. The highest phytoextraction enhancement was caused by Pseudomonas
      fluorescens MH15 which increased Zn, Cd and Cu accumulation in shoot tissue by
      60%, 96% and 31%, respectively, in comparison with control plants. Moreover, all
      the tested strains also exhibited a significant increase of Cd translocation from
      roots to shoots of the white mustard. Three Pseudomonas putida (MH3, MH6, MH7)
      and two P. fluorescens biotype G and C (MH9 and MH15, respectively) strains had
      the ability to produce siderophore, 1-amino-cyclopropane-1-carboxylic acid
      deaminase, indole 3-acetic acid as well as hydrocyanic acid. Additionally, P.
      putida strains were also capable of solubilizing inorganic phosphate. The ability
      of the tested strains to increase the metal uptake in white mustard and their
      plant growth-promoting properties make them good candidates for supporting heavy
      metal phytoextraction as well as for plant growth promoting.

PMID- 23561858
TI  - Understanding mechanotransduction and biotensegrity from an adaptation
      perspective.

PMID- 23561859
TI  - The effects of experience on the inter-reliability of osteopaths to detect
      changes in posterior superior iliac spine levels using a hidden heel wedge.
AB  - BACKGROUND: The use of palpation to diagnose musculoskeletal dysfunction is
      commonly taught within osteopathy and other manual therapies. However the
      clinical tests used to detect sacroiliac joint dysfunction have not shown good
      reliability. OBJECTIVES: To investigate the inter-examiner reliability of
      osteopaths to detect asymmetries of the posterior superior iliac spine (PSIS),
      and to determine if inter-examiner reliability was affected by the level of
      practitioner experience. METHODS: Fifteen final year osteopathic students (n =
      15), fifteen third year osteopathic students (n = 15) and ten experienced
      osteopaths (n = 10) manually palpated the levels of the PSIS in one model nine
      consecutive times. A hidden 5 mm heel wedge was used to alter the height of the
      PSIS which was hidden from the examiners. Scores were analysed using Fleiss Kappa
      (Fkappa) statistics and one way analysis of variance on ranks (ANOVA). RESULTS:
      All three groups produced Fkappa results below 0.4 (0.025-0.065), indicating poor
      inter-examiner reliability. Fkappa values less than 0.4 are considered to be
      clinically unreliable. ANOVA testing did not show any significant difference
      between groups. CONCLUSION: This study showed 'poor' inter-examiner reliability
      in detecting asymmetries of the PSIS. This is in accordance with other studies in
      the field. It is suggested that the inclusion of this osteopathic model within
      osteopathic education should be reviewed.

PMID- 23561860
TI  - Abdominal wall trigger point case study.
AB  - Myofascial trigger points (TrPs) are posited to be an element in the etiology of
      both musculoskeletal and visceral pain. However, the recognition of TrPs as a
      causative factor in a patient's pain presentation varies amongst physicians and
      therapists. When myofascial pain syndrome is responsible for a patient's
      condition and is not recognized by the patient's medical advisors, the patient
      may be put through a plethora of testing procedures to find the cause of the
      patient's pain, and prescribed medications in an effort to treat the patient's
      symptoms. The case review presented here involves a patient with severe anterior
      abdominal pain, with a history of Crohn's disease, who experienced a long and
      difficult medical process before a diagnosis of myofascial pain syndrome was
      made.

PMID- 23561861
TI  - Mechanosensitivity of the median nerve in patients with chronic carpal tunnel
      syndrome.
AB  - The aim was to investigate the relationship between the effects of median nerve
      strain during the elbow extension component of the upper limb neurodynamic test 1
      (ULNT1) and the evoked musculoskeletal changes. 11 patients with chronic carpal
      tunnel syndrome (CTS) and 11 matched asymptomatic controls participated in the
      study. In all subjects, elbow extension was carried out in both ULNT1 and neutral
      positions of the shoulder and arm. From these two starting positions a KIN
      COM((r)) dynamometer carried out passive elbow extension while EMG activity of 10
      arm and shoulder muscles, elbow-flexor resistive torque and elbow extension ROM
      were measured concurrently. The result showed that, in the ULNT1 position,
      increased EMG activity of the involved muscles, increased elbow extension
      resistive torque and pain responses occurred much earlier in the range of elbow
      extension in the CTS group compared to healthy controls. These findings
      demonstrated increased mechanosensitivity of the median nerve in CTS patients
      compared to healthy controls.

PMID- 23561862
TI  - Brachial artery blood flow during submaximal isometric contraction of the biceps
      brachii and triceps brachii in humans: a preliminary observation.
AB  - The purpose of this study was to evaluate brachial artery blood flow changes
      during submaximal isometric contraction of the biceps and triceps brachii, in
      order to clarify the influence of the upper arm muscles activity on the local
      arterial flow. The brachial artery blood flow velocity and diameter were
      evaluated in twenty healthy men (mean age 29.6 years) at baseline (resting
      position) and during submaximal isometric contraction of the biceps and triceps
      brachii by means of ultrasonography (B-MODE and Doppler ultrasound methods). The
      brachial artery blood flow velocity was significantly higher than resting
      position during submaximal isometric contraction of the biceps (P < 0.001) and
      triceps brachii (P = 0.019). As to the brachial artery diameter, no significant
      change was observed during submaximal isometric contractions of the biceps and
      triceps brachii. Our preliminary findings suggest that the brachial artery blood
      flow velocity similarly increases during submaximal isometric contraction of the
      biceps and triceps brachii.

PMID- 23561863
TI  - The physiotherapists' experience of Basic Body Awareness Therapy in patients with
      schizophrenia and schizophrenia spectrum disorders.
AB  - BACKGROUND: Scandinavian physiotherapists (PT) treat patients with schizophrenia
      and schizophrenia spectrum disorder, mainly because of the latter's bodily
      difficulties. One commonly used method is Basic Body Awareness Therapy (BBAT),
      targeting the difficulties with sensory motor dysfunction and disembodiment. The
      aim of the study is to describe the physiotherapist's experiences of using BBAT
      for patients with Schizophrenia. METHOD: In a qualitative study, eight
      physiotherapists, who use BBAT when treating patients with schizophrenia were
      interviewed. The interview transcriptions were analysed according to content
      analysis. RESULTS: Three stage related themes were created: "encountering"
      "discovery towards embodiment", and "inner space towards outer world". In
      "encountering" the PTs described important aspects at the beginning of treatment.
      "Discovery towards embodiment" revealed how the PTs conceived that the patients'
      attention is directed toward their own body and their bodily experiences. The
      theme, "inner space towards outer world" reflects the PTs experience of the
      changes achieved and how patients turn their attention to the outside world as a
      more competent self.

PMID- 23561864
TI  - Affective responses to qigong: a pilot study of regular practitioners.
AB  - Single sessions of Qigong have been associated with increased positive
      affect/emotional benefits. In the present study the aim was to refine the present
      understanding by using newly developed research methodologies. Therefore,
      affective reactions were studied in a group performing Qigong through pre-,
      during, and post-assessments using a modified version of the short Swedish Core
      Affect Scale complemented with open-ended questions. Affect was measured on a
      group and individual level. The results showed a shift during Qigong toward
      increased pleasant activated and deactivated affect in the group of 46 women who
      regularly practice Qigong. Inter-individual responses displayed positive
      affective responses, which also increased as the bout proceeded for the majority
      of practitioners. Acknowledging some limitations, these findings have practical
      implications for the enhancement of positive affect and subjective well-being.

PMID- 23561865
TI  - EMG activity of trunk stabilizer muscles during Centering Principle of Pilates
      Method.
AB  - This study aimed to analyze the electromyographic (EMG) activity of iliocostalis
      lumborum (IL), internal oblique (IO) and multifidus (MU) and the antagonist
      cocontraction (IO/MU and IO/IL) during the performance of Centering Principle of
      Pilates Method. Participating in this study were eighteen young and physically
      fit volunteers, without experience in Pilates Method, divided in two groups: low
      back pain group (LBPG, n = 8) and control group (CG, n = 10). Two isometric
      contractions of IO muscles (Centering Principle) were performed in upright
      sitting posture. EMG signal amplitude was calculated by Root Mean Square (RMS),
      which was normalized by RMS maximum value. The common area method to calculate
      the antagonist cocontraction index was used. MU and IO activation and IO/MU
      cocontraction (p < 0.05) were higher in CG. The CG therefore showed a higher
      stabilizer muscles recruitment than LBPG during the performance of Centering
      Principle of Pilates Method.

PMID- 23561866
TI  - The impact of load and base of support on electromyographic onset in the shoulder
      muscle during push-up exercises.
AB  - OBJECTIVE: To investigate the effects of base of support (BOS) and external loads
      on electromyographic (EMG) onset in the shoulder muscles during push-up
      exercises. METHODS: Two levels of external load were applied at two levels of BOS
      stability during push-up exercises. EMG onset in six shoulder muscles was
      measured in 30 healthy participants. RESULTS: With load set at 4% of body weight
      (BW), EMG onset in the lower trapezius (LT) (P = 0.003) and biceps brachia (BB)
      (P = 0.001) was significantly decreased with no load. Conversely, in other
      muscles (the upper trapezius (UT), teres major (TM), seratus anterior (SA) and
      deltoid posterior (DP)), time to EMG onset did not change significantly. No
      significant changes in EMG onset were observed with load at 2% of BW. The average
      time to EMG onset was significantly decreased for different stages of BOS
      instability in the LT (P = 0.04) and UT (P = 0.001). CONCLUSION: Both load and
      BOS instability reduce time to EMG onset, but BOS instability produces greater
      reductions.

PMID- 23561867
TI  - The variation of the strength of neck extensor muscles and semispinalis capitis
      muscle size with head and neck position.
AB  - Semispinalis capitis muscle (SECM) is a massive and long cervico-thoracic muscle
      which functions as a main head and neck extensor muscle. The aim of this study
      was to detect the effect of head and neck positions on the strength of neck
      extensor muscles and size of SECM in healthy subjects. Thirty healthy women
      students voluntarily participated in this study. An ultrasonography apparatus
      (Hitachi EUB 525) and a system of tension-meter were used to scan the right SECM
      at the level of third cervical spine and to measure the strength of neck extensor
      muscles at three head and neck positions. Neck extensor muscles were stronger in
      neutral than flexion or than extension positions while the size of SECM was
      larger in extension than neutral or than flexion position. The force generation
      capacity of the main neck extensor muscle was lower at two head and neck flexion
      and extension positions than neutral position.

PMID- 23561868
TI  - Effects of Pilates exercises on pain, functional status and quality of life in
      women with postmenopausal osteoporosis.
AB  - OBJECTIVE: The present study aimed to evaluate the effects of Pilates exercise
      program on pain, functional status and quality of life in women with
      postmenopausal osteoporosis. DESIGN: The study was performed as a randomized,
      prospective, controlled and single-blind trial. PARTICIPATIONS: Seventy women
      (age range, 45-65 years) with the diagnosis of postmenopausal osteoporosis were
      included. METHODS AND INTERVENTIONS: Patients were randomly allocated into two
      groups (home and Pilates exercise groups). Patients in the Pilates exercise group
      underwent a supervised Pilates exercise program twice a week for one year.
      Patients in the home exercise group were asked to perform a home exercise program
      consisting of thoracic extension exercises. Patients were evaluated at baseline
      and after one year of participation in the exercise programs. MAIN OUTCOME
      MEASUREMENTS: Visual Analog Scale for pain, six-minute walking and sit-to-stand
      tests for functional status, and the Qualeffo-41 Questionnaire and the Short Form
      36 (SF-36) for quality of life. Patients were also asked to report the number of
      falls during the intervention. RESULTS: At the end of the study, the results of
      60 patients were analyzed. A significant improvement was noted in all evaluation
      parameters at the end of the exercise program in the Pilates exercise group.
      Except for Qualeffo- Leisure Time Activities, SF-36 physical role limitation and
      emotional role limitation subscales, a significant improvement was noted in all
      other evaluation parameters at the end of the exercise program in the home
      exercise group. Improvement was significantly greater in the Pilates exercise
      group compared to the home exercise group in all parameters. CONCLUSION: Pilates
      exercises may be a safe and an effective treatment alternative for the quality of
      life in patients with postmenopausal osteoporosis.

PMID- 23561869
TI  - Shoulder functionality after manual therapy in subjects with shoulder impingement
      syndrome: a case series.
AB  - The aim of the study was to identify the differences in functionality of the
      upper limb in subjects suffering from shoulder impingement syndrome after
      intervention by two manual therapy protocols. Randomized, single-blind study with
      a sample of 22 subjects (58 +/- 10.86 years old) divided into two groups. The
      conventional-group (n = 11) received mobilizations of the shoulder and the
      experimental-group (n = 11) was treated with soft tissue techniques in the
      cervical and upper thoracic regions. These two groups received electrotherapy and
      postural advices. The treatment lasted three weeks (15 daily sessions of 1 h and
      30 min). Both active and passive range of motion (ROM) and self-perceived
      functionality of the upper limb (DASH questionnaire) were measured. The
      experimental group showed a significant improvement in the DASH scores and both
      groups improved mobility in the intra-group comparison pre-intervention versus
      post-intervention (p < .05), but not statistically significant differences were
      found in the between-group comparison (p > .05). Our results suggest that a
      combined treatment with electrotherapy, postural hygiene and manual therapy,
      regardless of the protocol, improves shoulder mobility and functionality.

PMID- 23561870
TI  - Taking stock of the evidence.

PMID- 23561871
TI  - Mechanistic basis of manual therapy in myofascial injuries. Sonoelastographic
      evolution control.
AB  - The term myofascia is referred to the skeleton of muscle fibres organized as an
      interconnected 3D network that surrounds and connects the musculoskeletal system.
      Extracellular matrix muscle is relevant in tissue structural support and
      transmission of mechanical signals between fibres and tendons. Acute and chronic
      musculoskeletal injuries (muscle strain) are one of the major problems faced by
      those who practice any type of sport, regardless of whether they are
      professionals or amateurs. Therapeutic boarding is of uncertain value in most
      cases because there are many contributing factors such as type, severity,
      functional implication of the damaged tissue, progression or risk of relapse.
      Different studies suggest that the musculoskeletal cell matrix is essential for
      the development, maintenance and regeneration of skeletal muscle. In this
      article, we highlight the action of "non-contractile" structures, in particular
      the myofascial system or muscle fascia, which can be responsible for the
      pathophysiology and healing process of muscular injuries. Manual therapy plays a
      predominant role in the treatment of these types of injuries and is key in the
      process of obtaining a scar capable of transmitting mechanical information. The
      scientific basis of this process is described in this article. Through real-time
      sonoelastography we have accurate information regarding the current stage of the
      repair process and, thus, guide our treatment at all times. Some new concepts are
      introduced, including local elasticity, the relationship between fascial
      pretension and the different stages of the physiological myofascia repair
      process, scar modelling technique, and sonoelastographic evolution control.

PMID- 23561872
TI  - Case study: use of vibration therapy in the treatment of diabetic peripheral
      small fiber neuropathy.
AB  - The aim of the study was to describe a case of type II diabetic peripheral small
      fiber neuropathic pain treated with whole body vibration therapy after a failed
      trial of conventional drugs and interventional pain management. A 64-year-old
      male had chronic diabetic peripheral neuropathic pain in his both feet for about
      2 years. The patient tried multiple pain medications and various interventional
      pain treatments without significant pain relief. After 4 weeks of vibration
      treatment, which targeted the feet the patient's pain level and gait patterns
      significantly improved. These findings illustrate the importance of considering
      whole body vibration as a complimentary treatment in patients with diabetic
      peripheral neuropathic pain.

PMID- 23561873
TI  - The primal nature of core function: in rehabilitation & performance conditioning.

PMID- 23561874
TI  - Fundamentals of core conditioning.

PMID- 23561875
TI  - Changes in lateral abdominal muscles' thickness immediately after the abdominal
      drawing-in maneuver and maximum expiration.
AB  - All lateral abdominal muscles contract more strongly during maximum expiration
      than during the abdominal drawing-in maneuver (ADIM). However, little is known
      about which of the lateral abdominal muscles is activated during maximum
      expiration. Thus, the purpose of this study is to quantify changes in the
      thickness of the lateral abdominal muscles immediately after the ADIM and maximum
      expiration. The thickness of the transverse abdominis (TrA), internal oblique
      (IO), and external oblique (EO) muscles was measured by ultrasound imaging in 30
      healthy men before and after the ADIM and maximum expiration. After the ADIM,
      there was no significant change in the thickness of the lateral abdominal
      muscles. After maximum expiration, the thickness of the TrA muscle significantly
      increased, and there was no significant change in the thickness of the IO and EO
      muscles. Thus, maximum expiration may be an effective method for TrA, rather than
      IO and EO, muscle training.

PMID- 23561876
TI  - Core exercises elevate trunk stability to facilitate skilled motor behavior of
      the upper extremities.
AB  - OBJECTIVE: The purpose of this study was to investigate the influence of core
      exercises on upper extremity function relative to skilled motor behavior and
      postural sway. METHOD: We examined the effects of core exercises on the skilled
      motor behavior and postural sway of 40 healthy students who were assigned
      randomly to the core exercise group or the control group. Independent variable is
      extent of exposure to core exercise and dependent variables are skilled motor
      behavior and postural sway. A Purdue pegboard which measures skilled motor
      behavior and a stabilometer which measures postural sway were used to evaluate
      the influence of core exercises. Pre-intervention and post-intervention skilled
      motor behavior and postural sway were compared between the core exercise group
      and control group using the Wilcoxon rank sum test; a significance level of alpha
      = 0.05 was considered statistically significant. Also, we investigated the
      application of core exercises in a clinical setting for one patient with cerebral
      vascular disease. RESULTS: The post intervention skilled motor behavior (p =
      0.04) and postural sway, LNG (p = 0.05), LNG/TIME (p = 0.04) and X LNG (p = 0.02)
      were significantly higher in the core exercise group than control group. In the
      case report, there were good results; function of the upper extremity improved
      after doing the exercises. There were positive changes in some daily living
      activities. DISCUSSION: Core exercises are likely to enhance trunk stabilization
      to improve upper extremity function. It is possible for core exercises to be
      adapted for patients.

PMID- 23561877
TI  - Training the hip: a progressive approach.
AB  - In this article a progressive series of exercises to enhance motor control or
      movement competency of the hip are described. The training begins with control of
      center of mass during forward leaning by the muscles of the sole of the foot.
      This progresses to a novel lunge exercise emphasizing eccentric quadriceps
      control the knee. Then gluteal training is shown in a modern variation on Tai Chi
      along with a hip stability exercise during trunk rolling movements.

PMID- 23561879
TI  - Substrain-specific differences in survival and osteonecrosis incidence in a mouse
      model.
AB  - We previously reported strain-specific susceptibility to dexamethasone-induced
      osteonecrosis in mice. Here we report that BALB/cJ and BALB/cAnNHsd mice display
      substrain-specific differences in dexamethasone-induced adverse effects. As
      compared with BALB/cJ mice, BALB/cAnNHsd weighed more (16.6 g compared with 13.7
      g) at the beginning of dexamethasone administration on postnatal day 28 and fewer
      died during the dexamethasone regimen (10% compared with 50%). Although the 2
      substrains had similar plasma concentrations of dexamethasone, BALB/cJ mice were
      more susceptible to developing dexamethasone-induced osteonecrosis. A higher dose
      of dexamethasone (8 mg/L) throughout the treatment period compared with a lower
      dose (8 mg/L loading dose during week 1 followed by 4 mg/L for the remainder of
      the treatment period) and earlier start of treatment (postnatal day 24 compared
      with postnatal day 28) was required to induce osteonecrosis with a similar
      frequency in BALB/cAnNHsd mice as in BALB/cJ mice. Our results show, for the
      first time, substrain-specific differences in the development of osteonecrosis in
      mice.

PMID- 23561878
TI  - Comparison of blood monocytes and adipose tissue macrophages in a mouse model
      diet-induced weight gain.
AB  - Diet-induced weight gain causes changes in adipose tissue that alter blood
      monocytes and adipose tissue macrophages, increasing disease risk. The purpose of
      this study was to compare the effects of 24 wk of diet-induced weight gain on the
      percentages of blood monocytes and adipose tissue macrophages as well as the cell
      surface expression of toll-like receptors 2 and 4 and leptin receptor, which are
      associated with inflammation and homing to adipose tissue. Crl:CD1(ICR) male mice
      were assigned to either a diet-induced weight gain (60% of calories from fat; n =
      12) or control (10% of calories from fat; n = 13) group. After 24 wk of dietary
      treatment, whole blood and bilateral perigonadal fat pads were collected. Whole
      blood or SVF were separately labeled for monocytes (CD11b(+)CD14-) or macrophages
      (CD11b(+)F4/80(+)) and receptor expression by using 3-color flow cytometry. Data
      were analyzed by using univariate ANOVA. Compared with control mice, those in the
      weight-gain group had greater body weight, fat mass, and percentages of monocytes
      and macrophages compared with CN. Regardless of cell type, monocytes and
      macrophages from mice in the weight-gain group expressed significantly less toll
      like receptor 2 and leptin receptor than did control mice. The present study
      demonstrates that monocytes and macrophages are similarly affected by diet
      induced weight gain. More research is needed to confirm how monocytes might be
      used as a proxy measure of macrophages.

PMID- 23561880
TI  - Transgenic rabbit models for studying human cardiovascular diseases.
AB  - Cardiovascular diseases involve the heart or blood vessels and remain a leading
      cause of morbidity and mortality in developed countries. A variety of animal
      models have been used to study cardiovascular diseases and have contributed to
      our understanding of their pathophysiology and treatment. However, mutations or
      abnormal expression of specific genes play important roles in the pathophysiology
      of some heart diseases, for which a closely similar animal model often is not
      naturally available. With the advent of techniques for specific genomic
      modification, several transgenic and knockout mouse models have been developed
      for cardiovascular conditions that result from spontaneous mutations. However,
      mouse and human heart show marked electrophysiologic differences. In addition,
      cardiac studies in mouse models are extremely difficult because of their small
      heart size and fast heart rate. Therefore, larger genetically engineered animal
      models are needed to overcome the limitations of the mouse models. This review
      summarizes the transgenic rabbit models that have been developed to study
      cardiovascular diseases.

PMID- 23561881
TI  - Complications of elastase-induced arterial saccular aneurysm in rabbits: case
      reports and literature review.
AB  - Endoluminal infusion and incubation of elastase with or without collagenase into
      the rabbit common carotid artery is an established model of arterial saccular
      aneurysm. The model mimics naturally occurring human cerebral aneurysms in many
      ways, including histologic and morphologic characteristics, hemodynamic
      pressures, and shear stresses. However, complications have been associated with
      the model. Here, we report 2 complications: 1) the first known case of iatrogenic
      laryngeal hemiplegia in a rabbit; and 2) histopathologically confirmed iatrogenic
      hippocampal and cerebellar infarcts (stroke). Finally, we present and review data
      from current literature on the morbidity and mortality associated with this
      model.

PMID- 23561882
TI  - Effects of mobilization regimens in donors on outcomes of hematopoietic cell
      transplantation in miniature Swine.
AB  - Toxicities and complications associated with hematopoietic cell transplantation
      currently limit this potentially curative therapy for malignant and nonmalignant
      blood disorders. Miniature swine provide a clinically relevant model for studies
      to improve posttransplantation outcomes. Miniature swine recipients of high-dose
      haploidentical hepatopoietic cell transplantation after reduced-intensity
      conditioning consisting of low-dose (100 cGy) total-body irradiation, partial T
      cell depletion by using a CD3 immunotoxin, and a 45-d course of cyclosporine A
      typically successfully engraft without graft-versus-host disease. We recently
      observed broad variability in engraftment outcomes that correlates with the
      occurrence of adverse reactions in donors after cytokine treatment to mobilize
      hematopoietic progenitor cells from the bone marrow to the peripheral blood for
      collection. Haploidentical recipients (n = 16) of cells from donors remaining
      healthy during cytokine treatment engrafted with multilineage chimerism, did not
      develop graft-versus-host disease, and did not require any blood products. In
      comparison, identically conditioned recipients of cells from donors that had
      severe reactions during cytokine treatment had adverse outcomes, including the
      development of clinically significant thrombocytopenia requiring blood product
      support in 8 of 11 swine. Furthermore, all 11 recipients lost peripheral blood
      myeloid chimerism (indicating lack of engraftment of donor stem cells). These
      data suggest that posttransplantation complications in swine are influenced by
      the health status of the donor before and during the collection of hematopoietic
      cells by leukapheresis.

PMID- 23561883
TI  - Inflammation in response to n3 fatty acids in a porcine obesity model.
AB  - Fatty acids have distinct cellular effects related to inflammation and insulin
      sensitivity. Dietary saturated fat activates toll-like receptor 4, which in turn
      can lead to chronic inflammation, insulin resistance, and adipose tissue
      macrophage infiltration. Conversely, n3 fatty acids are generally
      antiinflammatory and promote insulin sensitivity, in part via peroxisome
      proliferator-activated receptor gamma. Ossabaw swine are a useful biomedical
      model of obesity. We fed Ossabaw pigs either a low-fat control diet or a diet
      containing high-fat palm oil with or without additional n3 fatty acids for 30 wk
      to investigate the effect of saturated fats and n3 fatty acids on obesity-linked
      inflammatory markers. The diet did not influence the inflammatory markers C
      reactive protein, TNFalpha, IL6, or IL12. In addition, n3 fatty acids attenuated
      the increase in inflammatory adipose tissue CD16(-)CD14(+) macrophages induced by
      high palm oil. High-fat diets with and without n3 fatty acids both induced
      hyperglycemia without hyperinsulinemia. The high-fat only group but not the high
      fat group with n3 fatty acids showed reduced insulin sensitivity in response to
      insulin challenge. This effect was not mediated by decreased phosphorylation of
      protein kinase B. Therefore, in obese Ossabaw swine, n3 fatty acids partially
      attenuate insulin resistance but only marginally change inflammatory status and
      macrophage phenotype in adipose tissue.

PMID- 23561884
TI  - Using the noninvasive (13)C-sucrose breath test to measure intestinal sucrase
      activity in swine.
AB  - The sucrose breath test (SBT) is a simple noninvasive technique used currently to
      determine intestinal absorptive function in humans and rodents. However, to date,
      the test has not been adapted for use in swine. During weaning, intestinal
      sucrase activity in piglets temporarily declines in response to stressors and is
      commonly used as a marker of the intestinal response to weaning. Here we assessed
      the sucrose dose needed for using the SBT in piglets. Six randomly allocated
      piglets were orogastrically gavaged with (13)C-labeled sucrose at a dose of 2
      g/kg; breath samples were collected for measurement of (13)CO2 on days 0
      (approximately 17 h after weaning), 5, and 10 after weaning. The resultant SBT
      value (cumulative dose at 90 min) was decreased by 46% on day 5 after weaning
      relative to baseline levels, consistent with temporal changes in gastrointestinal
      sucrase activity associated with weaning. We conclude that a sucrose dose of 2
      g/kg is satisfactory to conduct SBT studies in piglets. With further development,
      the SBT may provide a new tool to noninvasively monitor digestive function in
      weaned piglets, to assess the effects of nutritional strategies on intestinal
      health, and as an indicator of gut integrity and function in swine models of
      human gastrointestinal disease.

PMID- 23561885
TI  - Iron indices in bottlenose dolphins (Tursiops truncatus).
AB  - Bottlenose dolphins can have iron overload (that is, hemochromatosis), and
      managed populations of dolphins may be more susceptible to this disease than are
      wild dolphins. Serum iron, total iron-binding capacity (TIBC), transferrin
      saturation, and ferritin were measured in 181 samples from 141 dolphins in 2
      managed collections and 2 free-ranging populations. Although no iron indices
      increased with age among free-ranging dolphins, ferritin increased with age in
      managed collections. Dolphins from managed collections had higher iron, ferritin,
      and transferrin saturation values than did free-ranging dolphins. Dolphins with
      high serum iron (exceeding 300 MUg/dL) were more likely to have elevated ferritin
      but not ceruloplasmin or haptoglobin, demonstrating that high serum levels of
      iron are due to a true increase in total body iron. A time-series study of 4
      dolphins with hemochromatosis that were treated with phlebotomy demonstrated
      significant decreases in serum ferritin, iron, and TIBC between pre- and
      posttreatment samples; transferrin saturation initially fell but returned to
      prephlebotomy levels by 6 mo after treatment. Compared with those in managed
      collections, wild dolphins were 15 times more likely to have low serum iron (100
      MUg/dL or less), and this measure was associated with lower haptoglobin. In
      conclusion, bottlenose dolphins in managed collections are more likely to have
      greater iron stores than are free-ranging dolphins. Determining why this
      situation occurs among some dolphin populations and not others may improve the
      treatment of hemochromatosis in dolphins and provide clues to causes of
      nonhereditary hemochromatosis in humans.

PMID- 23561886
TI  - Reassessing the detection of B-virus-specific serum antibodies.
AB  - B virus, a natural pathogen of macaques, can cause a fatal zoonotic disease in
      humans. Serologic screening of macaques by titration ELISA (tELISA, screening
      test) and by Western blot analysis (WBA, confirmatory test) is one of the
      principle measures to prevent human infection. Here we slightly modified these 2
      tests and reevaluated their correlation. We developed a high-throughput tELISA
      and used it to screen 278 sera simultaneously against the homologous BV antigen
      and the heterologous antigens of Papiine herpesvirus 2 and Human herpesvirus 1.
      More sera (35.6%) were positive by the BV-ELISA than by the HVP2-ELISA (21.6%) or
      HSV1-ELISA (19.8%). The superiority of the homologous tELISA over the
      heterologous tELISA was prominent in low-titer sera. WBA confirmed only 21% of
      the tELISA-positive sera with low or intermediate antibody titers. These sera
      might have contained antibodies to conformational epitopes that could not be
      detected by WBA, in which denatured antigens are used, but that could be detected
      by tELISA, which detects both linear and conformational epitopes. WBA confirmed
      82% of the tELISA high-titer sera. However, WBA defined the remaining 18% of
      sera, which were negative by tELISA, as nonnegative. This finding can be
      attributed to the difficulties encountered with the subjective interpretation of
      results by WBA. Together, the current results indicate the inadequacy of WBA as a
      confirmatory assay for sera with low antibody titers.

PMID- 23561888
TI  - Epidemiology and characterization of seizures in a pedigreed baboon colony.
AB  - This study evaluated the incidence, prevalence, and clinical features of seizures
      in a pedigreed captive colony of baboons. The association of seizures with
      subspecies, age, sex, and various clinical features was assessed. Records for
      1527 captive, pedigreed baboons were reviewed, and 3389 events were identified in
      1098 baboons. Of these events, 1537 (45%) represented witnessed seizures, whereas
      the remaining 1852 presented with craniofacial trauma or episodic changes in
      behavior that were suggestive, but not diagnostic, of seizure activity. Seizures
      were generalized myoclonic or tonic-clonic, with two thirds of the events
      witnessed in the morning. Seizure onset occurred in adolescence (age, 5 y), with
      an average of 3 seizures in a lifetime. The incidence and prevalence of seizures
      were 2.5% and 26%, respectively, whereas the prevalence of recurrent seizures
      (that is, epilepsy) was 15%. Seizures were more prevalent in male baboons, which
      tended to present with earlier onset and more seizures over a lifetime than did
      female baboons. Seizures were equally distributed between the subspecies; age of
      onset and seizure recurrences did not differ significantly between subspecies.
      Clinical features including age of onset, characteristics, and diurnal
      presentation of seizures in baboons suggested similarities to juvenile myoclonic
      epilepsy in humans. Facial trauma may be useful marker for epilepsy in baboons,
      but its specificity should be characterized.

PMID- 23561887
TI  - An automated ELISA using recombinant antigens for serologic diagnosis of B virus
      infections in macaques.
AB  - B virus (Macacine herpesvirus 1) occurs naturally in macaques and can cause
      lethal zoonotic infections in humans. Detection of B virus (BV) antibodies in
      macaques is essential for the development of SPF breeding colonies and for
      diagnosing infection in macaques that are involved in human exposures.
      Traditionally, BV infections are monitored for presence of antibodies by ELISA (a
      screening assay) and western blot analysis (WBA; a confirmatory test). Both tests
      use lysates of infected cells as antigens. Because WBA often fails to confirm the
      presence of low-titer serum antibodies detected by ELISA, we examined a
      recombinant-based ELISA as a potential alternative confirmatory test. We compared
      a high-throughput ELISA using 384-well plates for simultaneous antibody screening
      against 4 BV-related, recombinant proteins with the standard ELISA and WBA. The
      recombinant ELISA results confirmed more ELISA-positive sera than did WBA. The
      superiority of the recombinant ELISA over WBA was particularly prominent for sera
      with low (<500 ELISA units) antibody titers. Among low-titer sera, the relative
      sensitivity of the recombinant ELISA ranged from 36.7% to 45.0% as compared with
      3.3% to 10.0% for WBA. In addition, the screening and confirmatory assays can be
      run simultaneously, providing results more rapidly. We conclude that the
      recombinant ELISA is an effective replacement for WBA as a confirmatory assay for
      the evaluation of macaque serum antibodies to BV.

PMID- 23561889
TI  - Excision of femoral head and neck for treatment of coxofemoral degenerative joint
      disease in a rhesus macaque (Macaca mulatta).
AB  - Nonhuman primates are a valuable model for osteoarthritis. Osteoarthritis has
      been extensively studied in nonhuman primates in both naturally occurring and
      induced disease states. However, little published information describes naturally
      occurring osteoarthritis of the coxofemoral joints of nonhuman primates. We
      report a case of naturally occurring coxofemoral joint osteoarthritis in a rhesus
      macaque. This case radiographically resembled hip dysplasia reported in other
      species and demonstrated a rapid progression in severity of lameness, with
      accompanying loss of muscle mass in the affected limb. We excised the femoral
      head and neck to alleviate the pain that accompanied the osteoarthritis. Physical
      therapy was initiated, and dual-energy X-ray absorptiometry and video recordings
      were performed to evaluate the macaque's response to surgical intervention. By 3
      mo postoperatively, the macaque had regained full use of the affected limb.

PMID- 23561890
TI  - Obstructive uropathy secondary to uterine leiomyoma in a chimpanzee (Pan
      troglodytes).
AB  - Complications due to uterine leiomyomata in chimpanzees have rarely been
      documented. Here we describe a female chimpanzee that developed severe
      hydronephrosis in the right kidney due to leiomyoma. Because hysterectomy did not
      alleviate the hydronephrosis, nephrectomy was elected. After these procedures,
      the chimpanzee is doing well. Leiomyomata screening programs with treatment
      algorithms are a useful component of a comprehensive chimpanzee program.

PMID- 23561891
TI  - Feline panleukopenia virus: its interesting evolution and current problems in
      immunoprophylaxis against a serious pathogen.
AB  - Vaccination of cats against feline panleukopenia virus (FPV) has been a routine
      part of feline medicine for the past 40 or more years, and many of the same
      vaccines that were first developed in the 1960s are still in routine use today.
      However, there has been significant evolution of the virus in the last 40 years,
      in particular the emergence of canine parvovirus (CPV) in dogs in the late 1970s,
      which was a host range variant of the FPV-like virus, and the world-wide spread
      of the CPV-derived viruses since 1978. FPV and the various antigenic types of CPV
      have been isolated from cats, raccoons, and many different wild and captive
      carnivores. The consequences of these changes in the viral populations have not
      been investigated, and the effectiveness of the current vaccine protocols have
      not been reported. Here we review the recent findings about the evolution of the
      viruses in carnivores including cats, and describe a study that looks at the
      efficiency of vaccination of kittens using the standard protocols, which shows
      that many cats are not protected by those approaches.

PMID- 23561892
TI  - CD40 ligand as a potential biomarker for atherosclerotic instability.
AB  - OBJECTIVE: The signaling protein CD40 and its ligand, CD40L, are thought to
      contribute to atherosclerotic plaque formation and rupture. We sought to
      determine their utility as markers of cerebral atherosclerosis and neurological
      dysfunction. METHODS: We recruited 82 patients with acute cerebral infarction
      (ACI) and classified each as having large-artery atherosclerosis (LAA, 30), small
      artery occlusion (36), or cardioaortic embolism (16). We also recruited 17
      patients who had carotid artery stenosis (CAS) without stroke and 20 healthy
      individuals as controls. CD40L expression on peripheral blood monocytes (PBMCs)
      was detected by direct immunofluorescence with flow cytometry, and serum soluble
      CD40L (sCD40L) was measured by ELISA. RESULTS: CD40L expression on PBMCs was
      highest in the LAA group, followed by that in the CAS group (both P < 0.01 versus
      control). It was also higher in patients with atherosclerotic infarction than in
      those without atherosclerosis (P < 0.05). PBMC CD40L expression was sensitive and
      specific for detecting atherosclerosis and LAA cerebral infarction and was
      superior to serum C-reactive protein for predicting cerebral atherosclerosis (P <
      0.01). Serum sCD40L was higher in patients with ACI than in healthy controls (P <
      0.01) or patients with CAS (P < 0.01) and correlated with increased disability on
      three scales (all P < 0.01). CONCLUSIONS: We conclude that patients with ACI have
      an upregulated CD40-CD40L system, which could be used as a clinical biomarker for
      assessing atherosclerotic instability and severity of neurological dysfunction.

PMID- 23561893
TI  - Efficiency of statin treatment on EPC recruitment depends on baseline EPC titer
      and does not improve angiographic outcome in coronary artery disease patients
      treated with the Genous stent.
AB  - The objective of this study was to assess the effect of high-dose atorvastatin
      treatment on endothelial progenitor cell (EPC) recruitment and angiographic and
      clinical outcome in coronary artery disease (CAD) patients treated with the
      Genous EPC-capturing stent. The HEALING IIB study was a multicenter, open-label,
      prospective trial that enrolled 100 patients. Patients were started on 80 mg
      atorvastatin qd, at least 2 weeks before the index procedure and continued for at
      least 4 weeks after the index procedure. Eighty-seven patients were included in
      this analysis. EPC levels significantly increased as early as 2 weeks after the
      start of atorvastatin. Remarkably, among this group, 31 patients proved to be
      nonresponders to atorvastatin treatment (i.e., no increase in EPC levels), while
      56 patients were responders (i.e., rise in EPC count between week -2 and 0).
      Compared to responders, nonresponders had a significantly higher baseline EPC
      count (76 +/- 10 vs. 41 +/- 5, p < 0.01) with a lower late luminal loss (LLL) at
      6- and 18-month follow-up (FU) (0.61 +/- 0.07 vs. 0.88 +/- 0.08, p < 0.05, and
      0.50 +/- 0.08 vs. 0.82 +/- 0.08, p < 0.01 respectively). Furthermore, baseline
      EPC count was inversely correlated with LLL at 6-month FU (R = -0.42, p < 0.001).
      Patients with a higher EPC count at baseline showed no increase in EPC
      recruitment in response to statin treatment but had favorable LLL at 6- and 18
      month FU, whereas patients with lower EPC count were responsive to statin
      therapy, but EPCs might be less functional as they had higher LLL at 6- and 18
      month FU. These data imply that although statin treatment can enhance EPC titer
      in patients with low baseline levels, there is no indication for a possible
      beneficial clinical effect with EPC capture stents.

PMID- 23561894
TI  - Longitudinal associations between HIV risk reduction and out-of-school time
      program participation.
AB  - PURPOSE: The study aimed to determine the longitudinal associations between
      several variables assessing positive youth development and HIV risk-reduction
      practices. METHODS: Participants were 329 youth enrolled in out-of-school time
      programs in New York City. Longitudinal data were collected in three waves during
      2008-2009 (baseline, 6-month follow-up, and 12-month follow-up). Because of the
      nested nature of the data, multivariate analyses were performed using multilevel
      models. RESULTS: At baseline, HIV risk reduction was associated with female
      gender, greater individual-level program participation, and greater school
      connectedness. Over time, HIV risk reduction was associated with program-level
      participation: Individuals in groups with program-level participation scores 1
      standard deviation below the average showed significant declines in risk
      reduction practices over the 1-year study period compared with individuals in
      more participatory programs. CONCLUSIONS: This study provides support for the out
      of-school environment as an important context for sustaining HIV risk reduction
      and positive health promotion practices.

PMID- 23561895
TI  - "I'm the one taking it": adolescent participation in chronic disease treatment
      decisions.
AB  - PURPOSE: To understand adolescents' roles and preferences in chronic disease
      treatment decisions, using biologic therapy decisions as an example. METHODS: We
      conducted semistructured interviews with adolescents who have Crohn's disease (n
      = 7) or juvenile idiopathic arthritis (n = 8). Questions focused on biologic
      therapy decisions, including who participated, preferred roles, and factors
      considered in the decision. We used pie charts to help teens describe the
      division of decisional responsibility. We open-coded the initial interviews to
      develop a coding structure. Interviews then were coded by two people, with
      disagreements resolved through discussion. Interviews were analyzed using content
      analysis. RESULTS: Nearly all adolescents participated in the decision about
      biologic therapy. Roles varied from telling parents about specific symptoms to
      having the final say in the decision. In addition to discussing their own roles,
      adolescents identified specific decision-making roles for both parents and
      physicians. Most factors that influenced adolescents' decision-making related to
      their quality of life, such as the desire to feel better, concerns about painful
      injections, and the time needed for treatment. Some adolescents did consider
      potential side effects and the expected treatment efficacy. Most adolescents were
      satisfied with how the decision was made, but given a choice would have preferred
      a different role in the decision. CONCLUSION: Adolescents with chronic disease
      wish to be involved in treatment decision making, but also seek the involvement
      of parents and physicians. Parents and providers can assist by providing
      adolescents with relevant information and by helping teens develop the skills
      necessary for future medical decision-making.

PMID- 23561896
TI  - Acute kidney injury during therapy with an antisense oligonucleotide directed
      against PCSK9.
AB  - Antisense oligonucleotides have been explored widely in clinical trials and
      generally are considered to be nontoxic for the kidney, even at high
      concentrations. We report a case of toxic acute tubular injury in a healthy 56
      year-old female volunteer after a pharmacologically active dose of a locked
      nucleic acid antisense oligonucleotide was administered. The patient received 3
      weekly subcutaneous doses of experimental drug SPC5001, an antisense
      oligonucleotide directed against PCSK9 (proprotein convertase subtilisin/kexin
      type 9) that is under investigation as an agent to reduce low-density lipoprotein
      cholesterol levels. Five days after the last dose, the patient's serum creatinine
      level increased from 0.81 mg/dL at baseline (corresponding to an estimated
      glomerular filtration rate [eGFR] of 78 mL/min/1.73 m(2)) to 2.67 mg/dL (eGFR, 20
      mL/min/1.73 m(2)), and this increase coincided with the presence of white blood
      cells, granular casts, and minimal hematuria on urine microscopy. The patient's
      serum creatinine level peaked at 3.81 mg/dL (eGFR, 13 mL/min/1.73 m(2)) 1 week
      after the last oligonucleotide dose. Kidney biopsy showed multifocal tubular
      necrosis and signs of oligonucleotide accumulation. Upon conservative treatment,
      the patient's serum creatinine level gradually decreased and reached her baseline
      level 44 days after the last oligonucleotide was administered. The patient
      recovered fully and kidney function was normal at every follow-up visit. 

PMID- 23561897
TI  - Imaging of the female urethral diverticulum.
AB  - Female urethral diverticulum is a localized out-pouching of the urethra that is
      becoming increasingly prevalent, but often poses a diagnostic challenge.
      Traditionally, conventional voiding cystourethrography has been used to make the
      preoperative diagnosis. With the development of higher-resolution images acquired
      through ultrasonography (US), computed tomography (CT), and magnetic resonance
      imaging (MRI), the anatomy and various abnormalities of the female urethra can be
      better elucidated. This article focuses on the imaging features of female
      urethral diverticulum, with emphasis on diagnostic pearls, particularly using
      MRI. Female urethral diverticulum can be best identified by their location in the
      posterolateral urethra and by their communication with the urethral lumen.
      Improved imaging techniques combined with increased physician awareness of
      urethral diverticulum will lead to more prompt and accurate diagnosis of this
      entity, leading to better treatment of affected patients.

PMID- 23561898
TI  - Mid-palm hand amputation: reconstruction of the superficial palmar arch.

PMID- 23561899
TI  - [Crizotinib: a targeted therapy in advanced ALK-positive non-small cell lung
      cancer].
AB  - Crizotinib is a small orally-administered ALK inhibitor for patients with non
      small cell lung cancer with EML4-ALK rearrangement (echinoderm microtubule
      associated protein-like 4 and anaplastic lymphoma kinase). This fusion gene is
      detected with a break apart fluorescence in situ hybridization (FISH) assay.
      Phase I to III trials have shown an interesting disease control rate and
      acceptable tolerability. Crizotinib is available in France under temporary use
      authorization. New potentially effective therapeutics in ALK-positive NSCLC are
      being developed.

PMID- 23561900
TI  - [Evaluation of the management of COPD exacerbations: an audit in French emergency
      services].
AB  - INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
      patients are major events in the history of this chronic respiratory disease.
      Their management in French emergency services is unknown, although national
      guidelines exist. METHODS: This is a descriptive audit study, over a 10 weeks
      period (12/01-22/03/2009), of the management of COPD exacerbations in the RESUVal
      (Reseau des Urgences de la Vallee du Rhone, France) network emergency
      departments. RESULTS: The enrollement of 16 emergency units allowed the analysis
      of 221 exacerbations of COPD. Measurement of respiratory rate and description of
      the sputum were mentioned in only 99 (45%) medical records. The rest of the
      initial assessment was generally satisfactory. Regarding the therapeutic
      management, 215 (97%) patients received oxygen, beta-2-agonist aerosols were
      administrated for 209 (95%) patients and anticholinergic aerosols were used for
      176 (80%) patients. A systemic corticosteroid and antibiotics were respectively
      prescribed for 116 (52%) and 123 (56%) patients. Non-invasive ventilation (NIV)
      was used in only 59% of patients presenting a pH<7.35. CONCLUSIONS: These
      findings demonstrate that management of exacerbations of COPD could be improved
      through systematic patients' respiratory rate and sputum characteristics
      recording or NIV utilization reinforcement.

PMID- 23561901
TI  - Tutorial: simulating chromatography with Microsoft Excel Macros.
AB  - Chromatography is one of the cornerstones of modern analytical chemistry;
      developing an instinctive feeling for how chromatography works will be invaluable
      to future generation of chromatographers. Specialized software programs exist
      that handle and manipulate chromatographic data; there are also some that
      simulate chromatograms. However, the algorithm details of such software are not
      transparent to a beginner. In contrast, how spreadsheet tools like Microsoft
      ExcelTM work is well understood and the software is nearly universally available.
      We show that the simple repetition of an equilibration process at each plate (a
      spreadsheet row) followed by discrete movement of the mobile phase down by a row,
      easily automated by a subroutine (a "Macro" in Excel), readily simulates
      chromatography. The process is readily understood by a novice. Not only does this
      permit simulation of isocratic and simple single step gradient elution, linear or
      multistep gradients are also easily simulated. The versatility of a transparent
      and easily understandable computational platform further enables the simulation
      of complex but commonly encountered chromatographic scenarios such as the effects
      of nonlinear isotherms, active sites, column overloading, on-column analyte
      degradation, etc. These are not as easily simulated by available software. Views
      of the separation as it develops on the column and as it is seen by an end-column
      detector are both available in real time. Excel 2010TM also permits a 16-level (4
      bit) color gradation of numerical values in a column/row; this permits
      visualization of a band migrating down the column, much as Tswett may have
      originally observed, but in a numerical domain. All parameters of relevance
      (partition constants, elution conditions, etc.) are readily changed so their
      effects can be examined. Illustrative Excel spreadsheets are given in the
      Supporting Information; these are easily modified by the user or the user can
      write his/her own routine.

PMID- 23561902
TI  - Surface plasmon resonance sensing of nucleic acids: a review.
AB  - Biosensors based on surface plasmon resonance (SPR) have become a central tool
      for the investigation and quantification of biomolecules and their interactions.
      Nucleic acids (NAs) play a vital role in numerous biological processes and
      therefore have been one of the major groups of biomolecules targeted by the SPR
      biosensors. This paper discusses the advances of NA SPR biosensor technology and
      reviews its applications both in the research of molecular interactions involving
      NAs (NA-NA, NA-protein, NA-small molecule), as well as for the field of
      bioanalytics in the areas of food safety, medical diagnosis and environmental
      monitoring.

PMID- 23561903
TI  - High quality drug screening by capillary electrophoresis: a review.
AB  - High quality assays are needed in drug discovery to reduce the high attrition
      rate of lead compounds during primary screening. Capillary electrophoresis (CE)
      represents a versatile micro-separation technique for resolution of enzyme
      catalyzed reactions, including substrate(s), product(s), cofactor(s) and their
      stereoisomers, which is needed for reliable characterization of biomolecular
      interactions in free solution. This review article provides a critical overview
      of new advances in CE for drug screening over the past five years involving
      biologically relevant enzymes of therapeutic interest, including transferases,
      hydrolases, oxidoreductases, and isomerases. The basic principles and major
      configurations in CE, as well as data processing methods needed for rigorous
      characterization of enzyme inhibition are described. New developments in
      functional screening of small molecules that modulate the activity of disease
      related enzymes are also discussed. Although inhibition is a widely measured
      response in most enzyme assays, other important outcomes of ligand interactions
      on protein structure/function that impact the therapeutic potential of a drug
      will also be highlighted, such as enzyme stabilization, activation and/or
      catalytic uncoupling. CE offers a selective platform for drug screening that
      reduces false-positives while also enabling the analysis of low amounts of
      complex sample mixtures with minimal sample handling.

PMID- 23561904
TI  - Toward chromium speciation in solids using wavelength dispersive X-ray
      fluorescence spectrometry Cr Kbeta lines.
AB  - The determination of chromium speciation in solid samples is critical for
      environmental and industrial purposes. Several analytical methods exist to
      perform such a determination either directly in solid state or liquid state after
      an extraction step, each of them having some limitations. In this study, the use
      of a high-resolution wavelength-dispersive X-ray fluorescence spectrometer to
      determine and quantify chromium species is investigated by looking at the
      differences in the Kbeta transition profiles between Cr(0), Cr(III) and Cr(VI)
      compounds. Three different approaches were tested and compared to determine the
      Cr(VI) fraction of known mixtures: relative height and peak fitting using
      calibration mixtures, partial least square regression (PLS) of pure compounds,
      and principal component regression (PCR) of pure compounds. The accuracy of these
      methods was found to be about the same with an average relative error in the
      range of 15%. However, PLS and PCR can be easily implemented in an automated way
      contrary to peak fitting which can be sometimes perceived as analyst-dependant.
      Another advantage of using PLS and PCR is that information concerning the other
      oxidation states present in the sample can be retrieved. Finally, PLS and the
      peak height approach can be used up to 0.5% total chromium which make the XRF an
      alternative technique to X-ray induced photoelectron spectroscopy (XPS) for
      chromium speciation in solid state.

PMID- 23561905
TI  - Highly sensitive detection of urinary cadmium to assess personal exposure.
AB  - A series of Boron-Doped Diamond (BDD) ultramicroelectrode arrays were fabricated
      and investigated for their performance as electrochemical sensors to detect trace
      level metals such as cadmium. The steady-state diffusion behavior of these
      sensors was validated using cyclic voltammetry followed by electrochemical
      detection of cadmium in water and in human urine to demonstrate high sensitivity
      (>200 MUA ppb(-1) cm(-2)) and low background current (<4 nA). When an array of
      ultramicroelectrodes was positioned with optimal spacing, these BDD sensors
      showed a sigmoidal diffusion behavior. They also demonstrated high accuracy with
      linear dose dependence for quantification of cadmium in a certified reference
      river water sample from the U.S. National Institute of Standards and Technology
      (NIST) as well as in a human urine sample spiked with 0.25-1 ppb cadmium.

PMID- 23561906
TI  - One-way and two-way pulsed electromembrane extraction for trace analysis of amino
      acids in foods and biological samples.
AB  - In the present work, pulsed electromembrane extraction (PEME) was performed for
      the first time, as a new concept of electrically enhanced microextraction method,
      for extraction and quantification of histidine, phenylalanine and tryptophan in
      different matrices. PEME offers an alternative to conventional electromembrane
      extraction (EME), which faces problems such as serious instabilities in the
      analysis of real samples with high concentration levels of ions. In these
      samples, increasing of the ion transportation across the liquid membrane results
      in Joule heating during the extraction process which may follow by punctuation of
      the organic membrane, increasing of the current level and bubble formation due to
      electrolysis reactions. A mixture of 2-nitrophenyl octyl ether (NPOE), di-(2
      ethylhexyl) phosphate (DEHP) and tris-(2-ethylhexyl) phosphate (TEHP) was
      immobilized in the pores of hollow fiber as the organic liquid membrane. Other
      effective parameters such as extraction time, ion balance and pulse frequency
      were optimized using the experimental design. Extraction recoveries in the range
      of 7.1-21.6% and satisfactory repeatability (2.1<CV%<4.5) were obtained. Limits
      of detection were 5, 10 and 30 ng mL(-1) for tryptophan, phenylalanine and
      histidine, respectively. The method offers acceptable linearity with correlation
      coefficients higher than 0.9979. Furthermore, the figures of merit of PEME are
      compared with the results from conventional electromembrane extraction (EME),
      which proves the advantages of the proposed technique. The method was applied to
      the determination and quantification of amino acids in foods and biological
      samples. Also, two-way PEME was employed as a novel approach for highly selective
      extraction of tryptophan as a model analyte to introduce an interesting ability
      of the proposed technique.

PMID- 23561907
TI  - Determination of priority pollutants in aqueous samples by dispersive liquid
      liquid microextraction.
AB  - A dispersive liquid-liquid microextraction (DLLME) method followed by high
      performance liquid chromatography-triple quadrupole mass spectrometry has been
      developed for the simultaneous determination of linear alkylbenzene sulfonates
      (LAS C10, C11, C12, and C13), nonylphenol (NP), nonylphenol mono- and
      diethoxylates (NP1EO and NP2EO), and di-(2-ethylhexyl)phthalate (DEHP). The
      applicability of the method has been tested by the determination of the above
      mentioned organic pollutants in tap water and wastewater. Several parameters
      affecting DLLME, such as, the type and volume of the extraction and disperser
      solvents, sample pH, ionic strength and number of extractions, have been
      evaluated. Methanol (1.5 mL) was selected among the six disperser solvent tested.
      Dichlorobenzene (50 MUL) was selected among the four extraction solvent tested.
      Enrichment factor achieved was 80. Linear ranges in samples were 0.01-3.42 MUg L(
      1) for LAS C10-13 and NP2EO, 0.09-5.17 MUg L(-1) for NP1EO, 0.17-9.19 MUg L(-1)
      for NP and 0.40-17.9 MUg L(-1) for DEHP. Coefficients of correlation were higher
      than 0.997. Limits of quantitation in tap water and wastewater were in the ranges
      0.009-0.019 MUg L(-1) for LAS, 0.009-0.091 MUg L(-1) for NP, NP1EO and NP2EO and
      0.201-0.224 MUg L(-1) for DEHP. Extraction recoveries were in the range from 57
      to 80%, except for LAS C10 (30-36%). The method was successfully applied to the
      determination of these pollutants in tap water and effluent wastewater from
      Seville (South of Spain). The DLLME method developed is fast, easy to perform,
      requires low solvent volumes and allows the determination of the priority
      hazardous substances NP and DEHP (Directive 2008/105/EC).

PMID- 23561908
TI  - Determination of polycyclic and nitro musks in environmental water samples by
      means of microextraction by packed sorbents coupled to large volume injection-gas
      chromatography-mass spectrometry analysis.
AB  - In this work the development and validation of a new procedure for the
      simultaneous determination of 9 nitro and polycyclic musk compounds: musk
      ambrette (MA), musk ketone (MK), musk mosken (MM), celestolide (ADBI), phantolide
      (AHMI), tonalide (AHTN), traseolide (ATII), cashmeran (DPMI) and galaxolide
      (HHCB) in environmental water samples (estuarine and wastewater) using
      microextraction by packed sorbent (MEPS) followed by large volume injection-gas
      chromatography-mass spectrometry (LVI-GC-MS) was carried out. Apart from the
      optimization of the different variables affecting MEPS (i.e., nature of the
      sorbent, nature of the solvent elution, sample load, and elution/injection
      volume) extraction recovery was also evaluated, not only for water samples but
      also for environmental water matrices such as estuarine and waste water. The use
      of two deuterated analogs ([(2)H3]-AHTN and [(2)H15]-MX) was successfully
      evaluated in order to correct matrix effect in complex environmental matrices
      such as influent samples from wastewater treatment plants. Method detection
      limits (MDLs) ranged from 5 to 25 ng L(-1), 7 to 39 ng L(-1) and 8 to 84 ng L(-1)
      for influent, effluent and estuarine samples, respectively. Apparent recoveries
      were higher than 75% for all target compounds in all the matrices studied
      (estuarine water and wastewater) and the precision of the method, calculated as
      relative standard deviation (RSD), was below 13.2% at 200 ng L(-1) concentration
      level and below 14.9% at low level (20 ng L(-1) for all the target analytes,
      except for AHTN which was set at 40 ng L(-1) and HHCB at 90 ng L(-1), due to the
      higher MDL values presented by those target compounds). Finally, this MEPS
      procedure was applied to the determination of the target analytes in water
      samples, including estuarine and wastewater, from two estuaries, Urdaibai (Spain)
      and Adour (France) and an established stir-bar sorptive extraction-liquid
      desorption/large volume injection-gas chromatography-mass spectrometry (SBSE
      LD/LVI-GC-MS) method was performed in parallel for comparison. Results were in
      good agreement for all the analytes determined, except for DPMI.

PMID- 23561909
TI  - Relative quantification of enantiomers of chiral amines by high-throughput LC-ESI
      MS/MS using isotopic variants of light and heavy L-pyroglutamic acids as the
      derivatization reagents.
AB  - L-Pyroglutamic acid (L-PGA) was evaluated as a chiral labeling reagent for the
      enantioseparation of chiral amines in terms of separation efficiency by reversed
      phase chromatography and detection sensitivity by ESI-MS/MS. Several amines and
      amino acid methyl esters were used as typical representatives of the chiral
      amines. Both enantiomers of the chiral amines were easily labeled with L-PGAS at
      room temperature for 60 min in the presence of 1-(3-dimethylaminopropyl)-3
      ethylcarbodiimide and 1-hydroxy-1H-benzotriazole as the activation reagents. The
      resulting diastereomers were completely separated by reversed-phase
      chromatography using the small particle (1.7 MUm) ODS column (Rs=1.6-6.8). A
      highly sensitive detection at a low-fmol level (1-4 fmol) was also obtained from
      the multiple reaction monitoring (MRM) chromatograms. Therefore, a high
      throughput determination was achieved by the present UPLC-ESI-MS/MS method. An
      isotope labeling strategy using light and heavy L-PGAs for the differential
      analysis of chiral amines in different sample groups was also proposed in this
      paper. As a model study, the differential analysis of the R and S ratio of 1
      phenylethylamine (PEA) was performed according to the proposed procedure using
      light and heavy reagents, i.e., L-PGA and L-PGA-d5. The R/S ratio of PEA, spiked
      at the different concentrations in rat plasma, was almost similar to the
      theoretical values. Consequently, the proposed strategy using light and heavy
      chiral labeling reagents seems to be applicable for the differential analysis of
      chiral amine enantiomers in different sample groups, such as healthy persons and
      disease patients.

PMID- 23561910
TI  - Indium-tin-oxide thin film transistor biosensors for label-free detection of
      avian influenza virus H5N1.
AB  - As continuous outbreak of avian influenza (AI) has become a threat to human
      health, economic development and social stability, it is urgently necessary to
      detect the highly pathogenic avian influenza H5N1 virus quickly. In this study,
      we fabricated indium-tin-oxide thin-film transistors (ITO TFTs) on a glass
      substrate for the detecting of AI H5N1. The ITO TFT is fabricated by a one-shadow
      mask process in which a channel layer can be simultaneously self-assembled
      between ITO source/drain electrodes during magnetron sputtering deposition.
      Monoclonal anti-H5N1 antibodies specific for AI H5N1 virus were covalently
      immobilized on the ITO channel by (3-glycidoxypropyl)trimethoxysilane. The
      introduction of target AI H5N1 virus affected the electronic properties of the
      ITO TFT, which caused a change in the resultant threshold voltage (VT) and field
      effect mobility. The changes of ID-VG curves were consistent with an n-type field
      effect transistor behavior affected by nearby negatively charged AI H5N1 viruses.
      The transistor based sensor demonstrated high selectivity and stability for AI
      H5N1 virus sensing. The sensor showed linear response to AI H5N1 in the
      concentrations range from 5*10(-9) g mL(-1) to 5*10(-6) g mL(-1) with a detection
      limit of 0.8*10(-10) g mL(-1). Moreover, the ITO TFT biosensors can be repeatedly
      used through the washing processes. With its excellent electric properties and
      the potential for mass commercial production, ITO TFTs can be promising
      candidates for the development of label-free biosensors.

PMID- 23561911
TI  - On-line immunoaffinity capillary electrophoresis based on magnetic beads for the
      determination of alpha-1 acid glycoprotein isoforms profile to facilitate its use
      as biomarker.
AB  - An immunoaffinity purification method coupled on-line to capillary
      electrophoresis (IACE) which allows the determination of several isoforms of
      intact alpha-1 acid glycoprotein (AGP) in serum samples using UV detection is
      developed. The immunoaffinity step is based on anti-AGP antibodies (Abs)
      covalently bound to magnetic beads (MBs) which are captured at the inlet end of
      the capillary using permanent magnets placed inside the cartridge of the CE
      instrument. The on-line method includes injection of the MBs with the Ab bound
      (MBs-Ab) and their trapping by the magnets at the entrance of the separation
      column, injection of serum sample and capture of AGP by the Abs, release of
      captured AGP, focus of desorbed protein, separation of AGP isoforms, and removal
      of MBs-Ab. The optimization of the different factors involved in each step
      allowed purification, separation and detection of AGP isoforms in a single
      electrophoretic analysis in about 1 h. Automation, sample and reagents
      consumption as well as analysis time was improved compared to off-line
      alternatives which use purification of AGP in an immunochromatographic column and
      CE separation of AGP isoforms in two independent operations. The analytical
      methodology developed allows the separation of 10 AGP isoforms in serum samples
      from a healthy donor. For a serum sample, precision (expressed as relative
      standard deviation) in terms of corrected area percentage was better than 0.5%
      for each peak accounting for more than 10% of total AGP and it was better than
      4.0% in terms of relative migration time of each AGP isoform considering the
      whole process.

PMID- 23561912
TI  - Detailed elucidation of hydrocarbon contamination in food products by using solid
      phase extraction and comprehensive gas chromatography with dual detection.
AB  - The present work is focused on the development/optimization of a comprehensive
      two-dimensional gas chromatography method, with dual detection [flame ionization
      (FID) and mass spectrometric], for the simultaneous identification and
      quantification of mineral-oil contaminants in a variety of food products. The two
      main classes of contaminants, namely saturated and aromatic hydrocarbons, were
      previously fractionated on a manually-packed silver silica solid-phase extraction
      (SPE) cartridge. The quantitative results were compared with those obtained by
      performing a large volume injection, in a GC-FID system, after the same SPE
      process and by an on-line liquid-gas chromatography method, with very similar
      results observed. The presence of a series of unknown compounds, that appeared
      when using the off-line methods, was investigated using the mass spectrometric
      data, and were tentatively-identified as esterified fatty acids, most probably
      derived from vegetable oil based ink.

PMID- 23561913
TI  - Gross alpha and beta indices in water samples revisited.
AB  - Gross alpha and beta indices for water samples are generally determined
      simultaneously when a gas-flow proportional counter is used. The thickness of the
      source and the alpha-particle energy are factors of great importance due to self
      absorption or energy loss effects. Two variables have been studied: the use of
      different salts to produce standards with several thicknesses and the use of
      different radionuclides for the calibration process. Samples of known activity
      were prepared and measured for checking the procedures.

PMID- 23561914
TI  - Development of certified matrix reference materials for quality assurance of
      screening 134Cs and 137Cs in food.
AB  - A certified reference material using activated alumina powder certified for
      activity of (134)Cs and (137)Cs was developed. The results of the verification
      and the certification are described. The certified reference material can be used
      for quality assurance of screening activity measurements of (134)Cs and (137)Cs
      in food/foodstuffs. Commercially available equipments were experimentally tested
      using the CRM and another CRM including (40)K. The results of these tests are
      also shown.

PMID- 23561915
TI  - Emotion regulation through execution, observation, and imagery of emotional
      movements.
AB  - According to Damasio's somatic marker hypothesis, emotions are generated by
      conveying the current state of the body to the brain through interoceptive and
      proprioceptive afferent input. The resulting brain activation patterns represent
      unconscious emotions and correlate with subjective feelings. This proposition
      implies a corollary that the deliberate control of motor behavior could regulate
      feelings. We tested this possibility, hypothesizing that engaging in movements
      associated with a certain emotion would enhance that emotion and/or the
      corresponding valence. Furthermore, because motor imagery and observation are
      thought to activate the same mirror-neuron network engaged during motor
      execution, they might also activate the same emotional processing circuits,
      leading to similar emotional effects. Therefore, we measured the effects of motor
      execution, motor imagery and observation of whole-body dynamic expressions of
      emotions (happiness, sadness, fear) on affective state. All three tasks enhanced
      the corresponding affective state, indicating their potential to regulate
      emotions.

PMID- 23561916
TI  - Effects of combined application of muscle relaxants and celecoxib administration
      after total knee arthroplasty (TKA) on early recovery: a randomized, double
      blind, controlled study.
AB  - The purpose of this study was to evaluate the effectiveness of application of
      muscle relaxants and celecoxib in early recovery after total knee arthroplasty
      (TKA). One hundred and fifty patients were randomized 1:1:1 to receive either
      both of muscle relaxants and celecoxib or muscle relaxants alone or placebo for 2
      weeks (50 patients in each group). VAS pain scores as primary efficacy, active
      range of motion, morphine consumption, blood loss, and postoperative
      complications including postoperative nausea and vomiting (PONV), extremities
      myasthenia and deep vein thrombosis (DVT) were determined postoperatively. Group
      A improved better with reduced VAS pain scores compared with another two groups.
      These results demonstrated that application of muscle relaxants and celecoxib
      into patients undergoing TKA for 2 weeks postoperative consequently improved
      their convalescence.

PMID- 23561917
TI  - Systemic VEGF inhibition accelerates experimental atherosclerosis and disrupts
      endothelial homeostasis--implications for cardiovascular safety.
AB  - OBJECTIVES: This study sought to examine the effects and underlying mechanisms of
      systemic VEGF inhibition in experimental atherosclerosis and aortic endothelial
      cells. BACKGROUND: Pharmacological inhibition of vascular endothelial growth
      factor (VEGF), a major mediator of angiogenesis, has become a widely applied
      treatment of certain cancers and multiple ocular diseases including age-related
      macular degeneration. However, recent clinical trials raise concern for systemic
      vascular adverse effects, prompting the Food and Drug Administration to revoke
      the approval of bevacizumab for metastatic breast cancer. METHODS: Eight-week old
      apolipoprotein E knockout mice received a high-cholesterol diet (1.25%
      cholesterol) for 24 weeks and were exposed to a systemic pan-VEGF receptor
      inhibitor (PTK787/ZK222584, 50mg/kg/d) or placebo (gavage) for the last 10 weeks.
      Atherosclerotic lesions were characterized in thoraco-abdominal aortae and aortic
      arches. Mechanistic analyses were performed in cultured human aortic endothelial
      cells. RESULTS: Systemic VEGF inhibition increased atherosclerotic lesions by 33%
      whereas features of plaque vulnerability (i.e. necrotic core size, fibrous cap
      thickness) remained unchanged compared with controls. Aortic eNOS expression was
      decreased (trend). In human endothelial cells VEGF inhibition induced a dose
      dependent increase in mitochondrial superoxide generation with an uncoupling of
      eNOS, resulting in reduced NO availability and decreased proliferation.
      CONCLUSION: Systemic VEGF inhibition disrupts endothelial homeostasis and
      accelerates atherogenesis, suggesting that these events contribute to the
      clinical cardiovascular adverse events of VEGF-inhibiting therapies.
      Cardiovascular safety profiles of currently applied anti-angiogenic regimens
      should be determined to improve patient selection for therapy and allow close
      monitoring of patients at increased cardiovascular risk.

PMID- 23561918
TI  - Prevalence and outcomes of intermediate saphenous vein graft lesions: findings
      from the stenting of saphenous vein grafts randomized-controlled trial.
AB  - BACKGROUND: We sought to examine the prevalence and progression rate of
      intermediate saphenous vein graft (SVG) lesions in the Stenting Of Saphenous vein
      grafts (SOS) trial. METHODS: The baseline and follow-up angiograms of 80 patients
      participating in the SOS trial were analyzed to determine the prevalence of
      intermediate (30-60% angiographic diameter stenosis) SVG lesions and their
      progression rate. RESULTS: At least one intermediate SVG lesion was present in 31
      of 143 (22%) SVGs in 27 of 80 (34%) patients. Most intermediate lesions were
      present in the SOS stented SVGs (20 grafts in 19 patients). During a median
      follow-up of 35 months, angiographic follow-up was available for 28 grafts in 25
      patients. Progression (defined as percent diameter stenosis >= 70% but <100% at
      follow-up angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients
      (44%). Progression rate at 12, 24 and 36 months was 28% and 47% and 84%,
      respectively. Seven of 11 patients (64%) with intermediate SVG lesion progression
      presented with an acute coronary syndrome and 8 (73%) underwent PCI. Four of the
      28 grafts with intermediate lesions at baseline were 100% occluded at follow-up;
      all of those SVGs had received a stent in another location in the SVG as part of
      the SOS trial. CONCLUSIONS: Intermediate SVG lesions are common in patients
      undergoing SVG stenting, have high rates of progression and frequently present
      with an acute coronary syndrome. Further study of pharmacologic and mechanical
      treatments to prevent progression of these lesions is needed.

PMID- 23561919
TI  - High concentration of C-type natriuretic peptide promotes VEGF-dependent
      vasculogenesis in the remodeled region of infarcted swine heart with preserved
      left ventricular ejection fraction.
AB  - BACKGROUND: Vasculogenesis is a hallmark of myocardial restoration. Post-ischemic
      late remodeling is associated with pathology and function worsening. At the same
      time, neo-vasculogenesis helps function improving and requires the release of
      vascular endothelial growth factor type A (VEGF-A). The vasculogenic role of C
      type natriuretic peptide (CNP), a cardiac paracrine hormone, is unknown in
      infarcted hearts with preserved left ventricular (LV) ejection fraction (EF). We
      explored whether myocardial VEGF-dependent vasculogenesis is affected by CNP.
      METHODS AND RESULTS: To this end, infarcted swine hearts were investigated by
      magnetic resonance imaging (MRI), histological and molecular assays. At the
      fourth week, MRI showed that transmural myocardial infarction (MI) affected
      approximately 13% of the LV wall mass without impairing global function
      (LVEF>50%, n=9). Increased fibrosis, metalloproteases and capillary density were
      localized to the infarct border zone (BZ), and were associated with increased
      expression of CNP (p=0.03 vs. remote zone (RZ)), VEGF-A (p<0.001 vs. RZ), BNP, a
      marker of myocardial dysfunction (p<0.01 vs. RZ) and the endothelial marker,
      factor VIII-related antigen (p<0.01 vs. RZ). In vitro, CNP 1000 nM promoted VEGF
      dependent vasculogenesis without affecting the cell growth and survival, although
      CNP 100 nM or a high concentration of VEGF-A halted vascular growth. CONCLUSIONS:
      CNP expression is locally increased in infarct remodeled myocardium in the
      presence of dense capillary network. The vasculogenic response requires the co
      exposure to high concentration of CNP and VEGF-A. Our data will be helpful to
      develop combined myocardial delivery of CNP and VEGF-A genes in order to reverse
      the remodeling process.

PMID- 23561920
TI  - Concomitant dynamic obstruction and endocarditis after "valve in valve" TAVI
      implantation.

PMID- 23561921
TI  - Haemoptysis and pulmonary vein stenosis after ablation for atrial fibrillation:
      pathophysiology and therapeutic options.

PMID- 23561922
TI  - Clinical evaluation of a wireless ECG sensor system for arrhythmia diagnostic
      purposes.
AB  - In a clinical study, a novel wireless electrocardiogram (ECG) recorder has been
      evaluated with regard to its ability to perform arrhythmia diagnostics. As the
      ECG recorder will detect a "non-standard" ECG signal, it has been necessary to
      compare those signals to "standard" ECG recording signals in order to evaluate
      the arrhythmia detection ability of the new system. Simultaneous recording of ECG
      signals from both the new wireless ECG recorder and a conventional Holter
      recorder was compared by two independent cardiology specialists with regard to
      signal quality for performing arrhythmia diagnosis. In addition, calculated R-R
      intervals from the two systems were correlated. A total number of 16 patients
      participated in the study. It can be considered that recorded ECG signals
      obtained from the wireless ECG system had an acceptable quality for arrhythmia
      diagnosis. Some of the patients used the wireless sensor while doing physical
      sport activities, and the quality of the recorded ECG signals made it possible to
      perform arrhythmia diagnostics even under such conditions. Consequently, this
      makes possible improvements in correlating arrhythmias to physical activities.

PMID- 23561923
TI  - A magnetic resonance software simulator for the evaluation of myocardial
      deformation estimation.
AB  - This paper proposes a methodology to design a physiologically realistic computer
      simulator of images of the left ventricle myocardium based on a patient-specific
      biomechanical model. The simulator takes a magnetic resonance image of a given
      patient at end diastole, uses a manual segmentation of that image to model the
      geometry of the myocardium and sets the parameters of the constitutive model used
      for biomechanical simulation according to a regional labeling of the
      contractility of the myocardium for that patient. The simulated deformations are
      used to warp the magnetic resonance dataset throughout the cardiac cycle to
      generate different image modalities. The simulator is validated by quantifying
      its ability to model actual deformations in a set of patients affected by an
      acute myocardial infarction. Specifically a high correlation has been encountered
      between the ejection fraction derived from the simulated end systolic deformation
      of the myocardium and the myocardium segmented from actual data. Additionally,
      most of the parameters that describe the simulated deformation compare well with
      reported values. Overall, the simulator is intended as a testbed for extensive
      comparisons of myocardial motion tracking methods due to its ability to relate
      the impaired myocardial function with the associated ventricular remodeling, a
      novel contribution in the literature of cardiac image simulators. 

PMID- 23561924
TI  - Clinical utility of augmentation index as a new parameter of peripheral
      circulation in human fetuses.
AB  - BACKGROUND: Augmentation index (AI) is calculated from the central arterial
      pressure or pulse waveform and known as a parameter to evaluate arterial vascular
      function in adults. Patients with deterioration of peripheral circulation will
      demonstrate increased AI values as well as those with cardiovascular risks. It is
      because increased AI is caused by the early timing of the reflection wave from
      the periphery. On the other hand, in fetuses, although arterial pressure
      waveforms are not available, pulse waveforms of fetal descending aorta are
      recordable by using an echo-tracking system. Therefore in this study we aimed to
      evaluate the utility of fetal AI calculated from aortic pulse waveforms for
      detecting the altered peripheral circulation in human fetuses. STUDY DESIGN:
      Fetal AI was calculated from pulse waveforms in the descending aorta using an
      echo-tracking system. In a cross-sectional study of 105 normal fetuses, the
      reference range was constructed using linear regression analysis.
      Retrospectively, 36 growth-restricted fetuses were divided into 2 subgroups,
      normal (n=21) and increased AIx (n=15), based on the 90th percentile value of
      normal fetuses. Clinical parameters were compared using Fisher's exact test or
      Mann-Whitney U test. RESULTS: Fetal AI decreased linearly with advancing
      gestational age (r(2)=0.820). The incidences of umbilical artery absent/reversed
      end-diastolic flow, brain-sparing effect, and oligohydramnios were significantly
      higher in the increased AI group than the normal AI group. CONCLUSION: Fetal AI
      has a possibility to detect deteriorated peripheral circulation in the fetal body
      as well as fetoplacental circulation.

PMID- 23561925
TI  - Interrelationships among progesterone, LH, and luteal blood flow during a pulse
      of a PGF2alpha metabolite and functional role of LH in the progesterone rebound
      in heifers.
AB  - On Day 16 (Day 0 = ovulation) or before the expected transition into the
      luteolytic period, heifers were not treated (control group, N = 7) or were
      treated with a single 0.1-mg dose of estradiol (E2) (E2 group, N = 6) or E2
      combined with the GnRH antagonist acyline (E2/Ac group, N = 5). Hourly blood
      samples were collected from hour of treatment (Hour 0) to Hour 20. Estradiol
      induced a pulse of PGFM, but the peak of the pulse occurred 2 hours later (P <
      0.05) and mean PGFM concentrations during the descending portion of the pulse
      were lower (P < 0.05) in the E2/Ac group than in the E2 group. In the E2 group,
      concentration of progesterone (P4) decreased (P < 0.05) during the ascending
      portion of the PGFM pulse, and increased (rebounded; P < 0.05) along with an LH
      increase during the descending portion. In the E2/Ac group, a rebound in P4 and
      an increase in LH were not detected during the descending portion of the PGFM
      pulse. The percentage of CL with color Doppler signals of blood flow increased (P
      < 0.04) concurrently with the PGFM increase during Hours 0 to 5 and during the
      ascending portion of the PGFM pulse. Blood flow and PGFM decreased concurrently.
      The following hypotheses were supported: (1) LH has a positive effect on PGFM
      pulses; (2) the rebound in P4 and the increase in LH during the descending
      portion of a PGFM pulse are functionally related; and (3) the increase in luteal
      blood flow in association with a PGFM pulse represents a direct effect of
      PGF2alpha rather than an effect of P4 or LH.

PMID- 23561926
TI  - New seminal plasma removal method for freezing stallion semen.
AB  - Seminal plasma removal, an indispensable step in equine semen cryopreservation,
      is usually done by centrifugation, but this might cause mechanical damage to
      sperm. A new method for seminal plasma removal from stallion semen, namely a
      filter composed of a synthetic hydrophilic membrane (Sperm Filter, BotuPharma,
      Botucatu, Sao Paulo, Brazil), was recently proposed. The objective of this study
      was to test the use of the Sperm Filter in the removal of seminal plasma before
      freezing stallion semen. Ejaculates from 31 stallions were divided into two
      groups and cryopreserved. In group 1 (G1), seminal plasma was removed with the
      Sperm Filter, and in group 2 (G2), seminal plasma was removed by centrifugation
      (600*g for 10 minutes). There were no differences (P < 0.05) between G1 and G2 in
      sperm kinetic parameters or plasma membrane integrity before or after
      cryopreservation. However, sperm recovery rate was higher (P < 0.05) for G1
      versus G2 (mean +/- SD, 89.4 +/- 7.4% vs. 80.9 +/- 5.5%). Therefore, the Sperm
      Filter was as efficient as centrifugation in removing seminal plasma from the
      stallion ejaculate. However, filtering was more practical and had significantly
      fewer sperm lost than the centrifugation technique.

PMID- 23561927
TI  - The impact of outpatient priming for induction of labour on midwives' work
      demand, work autonomy and satisfaction.
AB  - BACKGROUND: Induction of labour often begins with the application of a priming
      agent to soften the cervix, generally requiring women to stay in hospital
      overnight (inpatient priming). An alternative is outpatient priming by a midwife,
      where women are allowed to go home following priming. This approach has the
      potential to impact, either positively or negatively, on the midwives involved.
      QUESTION: To what extent did the introduction of outpatient priming influence
      midwives' work demands, work autonomy, stress and job satisfaction. METHODS: A
      before-after study (with two separate cross-sectional samples) was conducted
      alongside a randomized controlled trial of outpatient versus inpatient priming,
      conducted at two metropolitan teaching hospitals in Australia. Midwives completed
      a questionnaire before the introduction of outpatient priming and again
      approximately two years later. FINDINGS: 208 midwives participated (response
      rates-time 1:81% (87/108); time 2:78% (121/156)). A mixed model analysis test of
      pre-post intervention differences found no changes in work demand, work autonomy
      and satisfaction. At time 2, over 80% of midwives reported that the introduction
      of the practice had reduced or made no difference to their work stress and
      workload, and 93% reported that outpatient priming had increased or had no impact
      on their job satisfaction. Furthermore, 97% of respondents were of the opinion
      that the option of outpatient priming should continue to be offered. CONCLUSION:
      Results suggest that outpatient priming for induction of labour is viable from a
      midwifery practice perspective, although more research is needed.

PMID- 23561928
TI  - Nucleosomes contribute to increase mesangial cell chemokine expression during the
      development of lupus nephritis.
AB  - Nucleosomes represent a set of major autoantigens in the induction of systemic
      lupus erythematosus (SLE), and appear to be essential for the development of
      lupus nephritis. Deposition of nucleosome-containing immune complexes within the
      mesangial matrix and activation of mesangial cells may be important in the
      progression of lupus nephritis from a "sleeping" minimal change disease state to
      a full blown disease state. This study investigated the renal cytokine profile
      both in vivo during the development of the disease in (NZBxNZW)F1 (B/W) mice, and
      in vitro in primary B/W mesangial cells stimulated with nucleosomes, nucleosome
      IgG complexes, and anti-dsDNA mAb respectively. Nucleosomes alone stimulated
      primary mesangial cells in a dose dependent manner. Of the chemokines produced by
      activated mesangial cells, CCL2, CCL7, CCL20, CXCL1, CXCL2 and CXCL5 were highly
      up-regulated compared to unstimulated cells. These chemokines were also increased
      in vivo in anti-dsDNA antibody positive and nephritic B/W kidneys, and was
      accompanied by infiltration of neutrophils, macrophages, T and B cells. This
      study provides a link between nucleosome-containing immune complexes, activation
      of mesangial cells, infiltration of effector cells and the development of lupus
      nephritis. Nucleosomes are pro-inflammatory and trigger innate immune responses,
      and thus are not only passive targets for autoantibodies but may play an active
      role in lupus pathogenesis. The removal or increased enzymatic destruction of
      nucleosomes, and/or the inhibition of mesangial cell activation may be possible
      treatment strategies in lupus nephritis.

PMID- 23561929
TI  - Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic
      arthritis.
AB  - To assess the role of interleukin (IL)-33 and ST2, the receptor for IL-33, in the
      pathogenesis of systemic juvenile idiopathic arthritis (s-JIA), we sequentially
      measured the serum levels of IL-33 and soluble ST2 (sST2) in patients with s-JIA
      and determined their correlation with measures of disease activity and severity.
      Twenty-four patients with s-JIA, 5 with rheumatoid factor positive polyarticular
      JIA (RF+poly-JIA), and 20 age-matched healthy controls (HCs) were analyzed. IL-33
      and sST2 levels were quantified in serum by enzyme-linked immunosorbent assays.
      Serum IL-33 levels in most patients with active s-JIA were below the lowest
      detection limit. Serum IL-33 levels in patients with RF+poly-JIA were
      significantly higher than those in patients with s-JIA and HC. Serum sST2 levels
      in patients during the active phase of s-JIA were much higher than those in
      patients with poly-JIA and HC. Serum sST2 levels in patients with s-JIA were
      significantly elevated even in the inactive phase, when other clinical parameters
      were normalized. Serum sST2 levels correlated positively with the clinical
      parameters of disease activity. These findings indicate that ST2 may be an
      important mediator in s-JIA. Serum sST2 levels in patients with s-JIA correlated
      with disease activity, suggesting a potential role as a promising indicator of
      disease activity.

PMID- 23561930
TI  - MRI characteristics of brainstem encephalitis in hand-foot-mouth disease induced
      by enterovirus type 71--will different MRI manifestations be helpful for
      prognosis?
AB  - The MRI characteristics of 21 HFMD patients with brainstem encephalitis resulting
      from EV71 infection were examined to identify lesion patterns helpful in disease
      classification and prognosis. The author reviewed the clinical and MRI data of 21
      children with brainstem encephalitis infected during the EV71 outbreak in Hainan,
      China from May 2008 to September 2010. Thirteen cases of brainstem encephalitis
      were classified as type I based on unilateral or bilateral symmetrical patch-like
      hyperintense T1 and T2 MRI signals restricted to the posterior brainstem. In a
      significant minority of these cases (6/13), damage to the spinal ventral horn was
      also found. Among these 13 type I cases, 2 patients died, 7 recovered fully, and
      4 suffered from various neurological sequelae. Eight cases were classified with
      type II brainstem encephalitis based on a vague, speckled hyperintense T1 and T2
      signal pattern in the posterior brainstem. Six of these patients recovered fully,
      and 2 cases suffered from mild sequelae. Reexamination by MRI revealed an
      enduring lesion in only one type II case, restricted to the medulla oblongata.
      The prognosis of type II cases was better than that of type I cases. The lesion
      pattern revealed by MRI can distinguish type I from type II brainstem
      encephalitis due to EV71 infection and may prove valuable for prognosis. While
      lesions were usually located in the tegmental part of the brainstem in both
      patient groups, type I cases also demonstrated spinal, thalamic, and cortical
      lesions.

PMID- 23561931
TI  - Early failure of cementless porous tantalum monoblock tibial components.
AB  - Patient selection for cementless knee arthroplasty (TKA) remains challenging. 106
      consecutive TKAs performed with a cementless porous tantalum tibial component of
      PS-design were reviewed. Nine failures (8 male/1 female) occurred at a mean 18
      months and demonstrated a characteristic failure mode of medial tibial collapse.
      The mean height of 72.5 inches in the failure group was greater than the 65.8
      inches in the well-functioning group (P<0.001). The mean weight of 260.4 lb in
      the failure group was greater than the 204.1 lb in the well-functioning group
      (P=0.006). The high early failure rate occurred predominantly in tall, heavy,
      male patients and may be related to medial tibial overload resulting from
      increased flexibility of the implant in this patient type.

PMID- 23561932
TI  - 7,12-dimethylbenz[a]anthracene-induced malignancies in a mouse model of
      menopause.
AB  - Ovarian cancer has a high mortality rate because there are few symptoms in early
      disease development. The incidence of ovarian cancer increases in women after
      menopause. Understanding early events in this disease can best be achieved by
      using animal models. Therefore, the objective of this study was to develop and
      track the onset of ovarian tumorigenesis in mice mimicking characteristics of
      postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d)
      received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause
      ovarian failure. Four months after VCD treatment, via surgical intervention, each
      mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or
      vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian
      neoplasms. The experimental groups were untreated controls (Con-Con), DMBA
      treatment only (Con-DMBA), VCD treatment only (VCD-Con), and VCD+DMBA-treated
      (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were
      collected for histologic and immunohistochemical evaluation. No tumors developed
      in Con-Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian
      failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5
      mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were
      epithelial in origin. Our findings confirm that inducing ovarian tumors in mice
      by chemical means is an effective method for studying early stages of tumor
      development that may be relevant to epithelial ovarian cancers that arise in
      postmenopausal women.

PMID- 23561933
TI  - Comparison of vascular leak syndrome in mice treated with IL21 or IL2.
AB  - Interleukin 21 (IL21) is a T-cell-derived 4-helix-bundle cytokine that has
      sequence homology to the IL2 family. Recombinant human interleukin 2 (rIL2) is
      approved for the treatment of metastatic melanoma and renal cell carcinoma.
      However, toxicity of rIL2, including induction of vascular leak syndrome (VLS),
      has limited use of this cytokine to a small proportion of eligible patients. Both
      rIL2 and murine IL21 (mIL21) have potent antitumor efficacy in murine models. The
      purpose of the current study was to compare the ability of mIL21 and rIL2 to
      induce vascular leakage in a mouse model. Pulmonary and hepatic uptake of Evans
      blue dye, serum cytokine levels, spleen cell immunophenotype, and histologic
      changes in lung and liver were evaluated to detect VLS. High-dose (200 MUg) rIL2
      treatment induced vascular leakage in mice, evidenced by inflammatory cell
      infiltration and fluid extravasation into the lung and liver and increased levels
      of TNFalpha, IFNgamma, IL5, MCP1, and IL6 in serum. In contrast, an equivalent
      dose of mIL21 resulted in minimal vascular leakage with no evidence of cytopenia
      or cytokine production. These results support the use of IL21 as a cancer
      immunotherapeutic agent, potentially providing an antitumor response without
      induction of VLS.

PMID- 23561934
TI  - Endpoint refinement for total body irradiation of C57BL/6 mice.
AB  - Acute radiation syndrome is a life-threatening condition that has the potential
      to affect large populations of humans. Although several animal models of this
      syndrome are available, the total-body-irradiated mouse has emerged as an
      important tool to evaluate the efficacy of prospective prophylaxis, mitigation,
      and treatment compounds. Despite the widespread use of this model, humane
      endpoints have not been clearly identified. To address this issue, we developed a
      cageside observation-based scoring system specifically for total-body-irradiated
      mice to assess the progression of clinical signs associated with acute radiation
      syndrome. Male C57BL/6 mice (n=175; age, 8 to 9 wk) received an anticipated LD50
      dose of radiation and were observed for progression of clinical signs of acute
      radiation syndrome for 30 d. All mice were scored individually through cageside
      observation of their body posture (score, 0 to 3), eye appearance (0 to 3), and
      activity level (0 to 3). Retrospective analysis of the score data indicated that
      death could be predicted accurately by using increasing cumulative scores (0 to
      9). Total scores of 6, 7, 8, and 9 were associated with mortality rates of 78.6%,
      86.4%, 93.3%, and 100%, respectively. Furthermore, scores of 6, 7, and 8
      predicted death within 3, 1.5, and 0.5 d, respectively. The use of this scoring
      system provides investigators and IACUCs with predictive humane, surrogate
      endpoints for total-body-irradiated mice. This system allows preemptive
      euthanasia of mice before they become moribund, thereby minimizing pain and
      distress associated with acute radiation syndrome and improving animal welfare.

PMID- 23561935
TI  - Spontaneous cardiac calcinosis in BALB/cByJ mice.
AB  - BALB/c mice are predisposed to dystrophic cardiac calcinosis-the mineralization
      of cardiac tissues, especially the right ventricular epicardium. In previous
      reports, the disease appeared in aged animals and had an unknown etiology. In the
      current study, we report a substrain of BALB/c mice (BALB/cByJ) that develops
      disease early and with high frequency. Here we analyzed hearts grossly to
      identify the presence and measure the severity of disease and to compare BALB/c
      substrains. Histologic analysis and fluorescent and immunofluorescent microscopy
      were used to characterize the calcinotic lesions. BALB/cByJ mice exhibited more
      frequent and severe calcium deposition than did BALB/c mice of other substrains
      (90% compared with 3% at 5 wk). At this age, lesions covered an average of 30% of
      the total ventricular surface area in BALB/cByJ mice, compared with less than 1%
      in other strains. In bone-marrow-chimeric mice, green fluorescent protein was
      used as a marker to show that the lesions contain an infiltration of cells of
      bone marrow origin. Lesion histology showed that calcium deposits were surrounded
      by fibrosis with interspersed immune cells. Lymphocytes, macrophages, and
      granulocytes were all present. Internalization of the gap-junction protein
      connexin 43 was observed in myocytes adjacent to lesions. In conclusion,
      BALB/cByJ mice exhibit more frequent and severe dystrophic cardiac calcinosis
      than do other BALB/c substrains. Our findings suggest that immune cells are
      actively recruited to lesions and that myocyte gap junctions are altered near
      lesions.

PMID- 23561936
TI  - Mouse mammary gland is refractory to the effects of ethanol after natural
      lactation.
AB  - Ethanol is a dietary factor that dose-dependently increases breast cancer risk in
      women. We previously have shown that ethanol increases mammary epithelial density
      through increased branching after dietary exposure during puberty in CD2/F1 mice.
      To extend these studies to parous mice in a breast cancer model, we used a
      transgenic mouse model of human parity-associated breast cancer, the FVB-MMTV
      Her2/Neu mouse, which overexpresses wildtype EGFR2, resulting in constitutive
      activation of growth signaling in the mammary epithelium. Here we describe the
      short-term effects of ethanol feeding on progression through involution. Mice
      were fed diets supplemented with 0%, 0.5%, 1%, or 2% ethanol for 4, 9, or 14 d
      starting on day 21 of lactation (that is, at the start of natural postlactational
      involution). Unlike peripubertal mice exposed to ethanol, postlactational dams
      showed no changes in body weight; liver, spleen, and kidney weights; and
      pathology. Ethanol exposure had no effect on mammary gland lobular density and
      adipocyte size throughout involution. Likewise, the infiltration of inflammatory
      cells and serum oxidized lipid species were unchanged by diet, suggesting that
      ethanol feeding had no effect on local inflammation (leukocyte infiltration) or
      systemic inflammation (oxidized lipids). In conclusion, ethanol exposure of
      parous dams had no effect on mammary gland structure or the regression of the
      lactating mammary gland to a resting state. The period of involution that follows
      natural lactation appears to be refractory to developmental effects of ethanol on
      mammary epithelium.

PMID- 23561937
TI  - Administration of dexamethasone to neonatal rats induces hypomyelination and
      changes in the morphology of oligodendrocyte precursors.
AB  - To examine whether hypomyelination in neonatal rats might be related to apoptosis
      of oligodendrocyte progenitors, we administered dexamethasone (0.5 mg/kg SC) to
      neonatal rats on postnatal (P) days 1 through 5. Immunofluorescent staining and
      Western blotting for myelin basic protein (MBP) were performed on P14.
      Morphologic changes associated with apoptotic death of oligodendrocyte
      progenitors were assessed by using immunofluorescent staining on P5 of surface
      markers present at different developmental stages of oligodendrocyte progenitors
      (O4 and O1) and by double-staining with terminal deoxynucleotidyl transferase
      mediated digoxigenin-dUTP nick end-labeling (TUNEL) and O4 or O1. Administration
      of dexamethasone to neonatal rats reduced the expression of MBP in the white
      matter by P14. In addition, dexamethasone reduced the expression of O4-positive
      cells, presumably preoligodendrocytes, in the corpus callosum and induced
      degenerative changes, such as cytoplasmic condensation and fragmented, tortuous
      processes, in oligodendrocyte progenitors, and increased the number of TUNEL
      positive pyknotic nuclei of oligodendrocyte progenitors. These findings suggest
      that the dexamethasone-induced decreased expression of MBP in the cerebral
      hemispheres of the neonatal rats is due to apoptotic degeneration of
      oligodendrocyte progenitors. Administration of dexamethasone during the critical
      period of brain development may increase the risk of apoptosis in oligodendrocyte
      progenitors, subsequently resulting in hypomyelination.

PMID- 23561938
TI  - Naturally occurring disseminated group B streptococcus infections in postnatal
      rats.
AB  - Group B Streptococcus (Streptococcus agalactiae, GBS) is a gram-positive
      commensal and occasional opportunistic pathogen of the human vaginal,
      respiratory, and intestinal tracts that can cause sepsis, pneumonia, or
      meningitis in human neonates, infants, and immunosuppressed persons. We report
      here on a spontaneous outbreak of postnatal GBS-associated disease in rats. Ten
      of 26 (38.5%) 21- to 24-d-old rat pups died or were euthanized due to a moribund
      state in a colony of rats transgenic for the human diphtheria toxin receptor on a
      Munich-Wistar-Fromter genetic background. Four pups had intralesional coccoid
      bacteria in various organs without accompanying inflammation. GBS was isolated
      from the liver of 2 of these pups and from skin abscesses in 3 littermates. A
      connection with the transgene could not be established. A treatment protocol was
      evaluated in the remaining breeding female rats. GBS is a potentially clinically
      significant spontaneous infection in various populations of research rats, with
      some features that resemble late-onset postnatal GBS infection in human infants.

PMID- 23561939
TI  - Spontaneous osteoblastic osteosarcoma in a Mongolian gerbil (Meriones
      unguiculatus).
AB  - Spontaneous neoplasms in Mongolian gerbils have an incidence of 20% to 26.8%, but
      osteosarcomas occur at a much lower rate. Here we report a 1-y-old Mongolian
      gerbil with a spontaneous osteosarcoma at the level of the proximal tibia, with
      metastases to the pectoral muscles and lungs. Grossly, the tibial mass
      obliterated the tibia and adjacent muscles, and an axillary mass with a bloody,
      cavitary center expanded the pectoral muscles. Microscopically, the tibial mass
      was an infiltrative, osteoblastic mesenchymal neoplasm, and the axillary mass was
      an anaplastic mesenchymal neoplasm with hemorrhage. The lung contained multiple
      metastatic foci. Immunohistochemistry for osteonectin was strongly positive in
      the tibial, axillary, and pulmonary metastases. Although osteosarcoma is the most
      common primary malignant bone neoplasm that occurs spontaneously in all
      laboratory and domestic animal species and humans, it arises less frequently than
      does other neoplasms. The current case of spontaneous osteoblastic osteosarcoma
      of the proximal tibia and metastases to the pectoral muscles and lung in a
      Mongolian gerbil is similar in presentation, histology, and predilection site of
      both osteoblastic and telangiectatic osteosarcomas in humans. In addition, this
      case is an unusual manifestation of osteosarcoma in the appendicular skeleton of
      a Mongolian gerbil.

PMID- 23561940
TI  - Mandibular fracture and necrotizing sialometaplasia in a rabbit.
AB  - A 7-mo-old female New Zealand white rabbit presented with hemorrhage of the
      gingiva surrounding a loose lower right incisor. Antemortem conventional
      radiographs revealed only a small bone fragment adjacent to the left mandible's
      body. In light of a provisional diagnosis of mandibular fracture, the rabbit was
      euthanized. Postmortem radiographs of the disarticulated mandible demonstrated
      mandibular symphyseal fracture and comminuted fracture of the ramus and body of
      the left mandible. According to histopathology, the left submandibular salivary
      gland had necrotizing sialometaplasia, a nonneoplastic condition of the salivary
      glands that is caused by ischemic infarction. Although rabbits have been used as
      animal models of mandibular fracture and necrotizing sialometaplasia, no
      nonexperimental case of such conditions had been reported previously.

PMID- 23561942
TI  - Residual stresses in Y-TZP crowns due to changes in the thermal contraction
      coefficient of veneers.
AB  - OBJECTIVE: To test the hypothesis that the difference in the coefficient of
      thermal contraction of the veneering porcelain above (alphaliquid) and below
      (alphasolid) its Tg plays an important role in stress development during a fast
      cooling protocol of Y-TZP crowns. METHODS: Three-dimensional finite element
      models of veneered Y-TZP crowns were developed. Heat transfer analyses were
      conducted with two cooling protocols: slow (group A) and fast (groups B-F).
      Calculated temperatures as a function of time were used to determine the thermal
      stresses. Porcelain alphasolid was kept constant while its alphaliquid was
      varied, creating different Deltaalpha/alphasolid conditions: 0, 1, 1.5, 2 and 3
      (groups B-F, respectively). Maximum (sigma1) and minimum (sigma3) residual
      principal stress distributions in the porcelain layer were compared. RESULTS: For
      the slowly cooled crown, positive sigma1 were observed in the porcelain,
      orientated perpendicular to the core-veneer interface ("radial" orientation).
      Simultaneously, negative sigma3 were observed within the porcelain, mostly in a
      hoop orientation ("hoop-arch"). For rapidly cooled crowns, stress patterns varied
      depending on Deltaalpha/alphasolid ratios. For groups B and C, the patterns were
      similar to those found in group A for sigma1 ("radial") and sigma3 ("hoop-arch").
      For groups D-F, stress distribution changed significantly, with sigma1 forming a
      "hoop-arch" pattern while sigma3 developed a "radial" pattern. SIGNIFICANCE: Hoop
      tensile stresses generated in the veneering layer during fast cooling protocols
      due to porcelain high Deltaalpha/alphasolid ratio will facilitate flaw
      propagation from the surface toward the core, which negatively affects the
      potential clinical longevity of a crown.

PMID- 23561941
TI  - Efficacy of oral fecal bacteriotherapy in rhesus macaques (Macaca mulatta) with
      chronic diarrhea.
AB  - Chronic diarrhea remains the principal burden in providing health care for
      nonhuman primates in biomedical research facilities. Although the exact etiology
      continues to puzzle nonhuman primate clinicians, recent research in humans has
      shown that restoring the indigenous microbial diversity may be successful in
      resolving cases of chronic diarrhea when other treatment modalities have failed.
      The process of restoring this microbial balance, known as fecal bacteriotherapy,
      uses the complete flora from a normal donor as a therapeutic probiotic mixture.
      In the current study, Indian-origin rhesus macaques were randomized into
      treatment (n=7) and control (n=6) groups to determine whether orally administered
      fecal bacteriotherapy would reduce the overall incidence of chronic diarrhea
      during a 60-d follow-up period in the treatment group compared with control
      macaques, which received a placebo. Although the treatment effect, determined by
      comparing the baseline fecal scores of the treatment and control groups, did not
      reach statistical significance, preprocedure and postprocedure fecal scores in
      the treatment group differed significantly. These findings are encouraging, and
      we hope that our study will motivate larger studies evaluating the use of fecal
      bacteriotherapy in nonhuman primates.

PMID- 23561944
TI  - Introducing a new generation indirect calorimeter for estimating energy
      requirements in adult intensive care unit patients: feasibility, practical
      considerations, and comparison with a mathematical equation.
AB  - PURPOSE: Indirect calorimetry (IC) is increasingly advocated for individualizing
      nutritional therapy in critically ill adult patients, but questions remain
      regarding its practical implementation. MATERIALS AND METHODS: During 12 weeks,
      we prospectively assessed utility and practical aspects of IC use. Adult medico
      surgical intensive care unit (ICU) patients were daily screened for malnutrition.
      Indirect calorimetry was planned in subjects considered unable to meet energy
      requirements on day 3 after admission. Measured energy expenditure (MEE) was
      compared with calculated (resting/total) energy expenditure. RESULTS: A total of
      940 evaluations were performed in 266 patients (age, 63+/-16 years; 59% males;
      Acute Physiology and Chronic Health Evaluation II score, 14+/-8). A total of 230
      patients (86.5%) were at risk for malnutrition, and in 118 of them, IC was
      indicated. Practical considerations precluded measurements in 72 cases (61%).
      Forty-six calorimetric evaluations revealed an MEE of 1649+/-544 kcal per 24
      hours that poorly correlated with calculated resting energy expenditure (r2=0.19)
      and calculated total energy expenditure (r2=0.20). Indirect calorimetry
      measurements were not time-consuming. CONCLUSIONS: Indirect calorimetry was
      indicated in half but effectively performed in only 20% of a representative
      intensive care unit population at risk for malnutrition. Correlation between MEE
      and CEE was poor. CLINICAL RELEVANCY STATEMENT: Indirect calorimetry is
      increasingly advocated for individualizing nutritional therapy in critically ill
      adult patients. Practical feasibility is tested in this study. Large differences
      between measured and calculated energy expenditure are observed. Together with
      patients' characteristics, feasibility results can guide clinicians or institutes
      in using IC in their daily clinical practice.

PMID- 23561943
TI  - Function of ram spermatozoa frozen in diluents supplemented with casein and
      vegetable oils.
AB  - The aim of this study was to assess biologically safer components as alternatives
      to egg yolk for the frozen storage of ram semen using casein, coconut or palm oil
      in either Salamon's diluent (S) or a swim-up medium (SU). Ejaculates were frozen
      as pellets and sperm motility (subjectively) and acrosome integrity (FITC-PNA/PI)
      by flow cytometry were assessed at 0, 3 and 6h after thawing and incubation at 37
      degrees C. Three experiments were done: different concentrations of palm oil (5%,
      10% and 20%); casein added as emulsifier and protective agent; and differences
      between egg yolk, coconut and palm oil in S and SU. 20% of oil added to SU
      accounted for a lesser percentage (P<0.05) of motile cells compared to rest while
      no differences were found between different oil levels on viable cells. When
      casein was added to diluents containing 5% of palm oil, no differences were found
      between palm or casein (P>0.05). No differences were found when S and SU were
      compared neither as groups nor between S alone and containing coconut or palm
      oil; however, SU alone yielded less motility than SU 5% coconut. However, in both
      groups, S and SU, egg yolk accounted for the greatest values in both bases. These
      results indicate that none of biologically safer media components (casein, palm
      or coconut oil) used in this study maintained the function of ram spermatozoa
      after freeze-thawing better than S-containing egg yolk. The application of
      vegetable oils as substitutes for egg yolk in diluents for the cryopreservation
      of ram spermatozoa requires further research.

PMID- 23561945
TI  - The effect of electrical muscle stimulation on the prevention of disuse muscle
      atrophy in patients with consciousness disturbance in the intensive care unit.
AB  - PURPOSE: Disuse atrophy of the lower limbs of patients with consciousness
      disturbance has often been recognized as "an unavoidable consequence," such that
      the mechanism was not investigated diligently. In this study, we examined the
      preventive effects of electrical muscle stimulation (EMS) against disuse atrophy
      of the lower limbs in patients in coma after stroke or traumatic brain injury in
      the intensive care unit. MATERIALS AND METHODS: We evaluated changes in cross
      sectional area of lower limb muscles weekly with computed tomography in 6 control
      group patients and 9 EMS group patients. Electrical muscle stimulation was
      performed daily from day 7 after admission. We evaluated the anterior thigh
      muscle compartment, posterior thigh muscle compartment, anterior leg muscle
      compartment, and posterior leg muscle compartment. RESULTS: In the control group,
      the decrease in cross-sectional area progressed in all compartments every week (P
      < .0001). Cross-sectional areas of all compartments at day 14 were significantly
      decreased in the control group compared with those in the EMS group at day 7 (P <
      .001). We were able to limit the rate of muscle atrophy as measured in the cross
      sectional areas to within 4% during the period of EMS (days 7-42) in 5 patients.
      The difference between the control and the EMS groups was statistically
      significant (P < .001). CONCLUSION: Electrical muscle stimulation is effective in
      the prevention of disuse muscle atrophy in patients with consciousness disorder.

PMID- 23561946
TI  - Doxepin and cognitive behavioural therapy for insomnia in patients with
      Parkinson's disease -- a randomized study.
AB  - INTRODUCTION: Although a variety of pharmacologic and non-pharmacologic
      treatments are effective for insomnia in the general population, insomnia in
      Parkinson's disease differs in important ways and may need different treatments.
      No studies have conclusively demonstrated effective insomnia treatments in
      Parkinson's disease. METHODS: We conducted a three-arm six-week randomized pilot
      study assessing non-pharmacologic treatment (cognitive behavioural therapy with
      bright light therapy) or doxepin (10 mg daily), compared to an inactive placebo
      in Parkinson's patients with insomnia. Sleep outcomes included insomnia scales,
      clinical global impression, sleep diaries and actigraphy. Secondary outcomes
      included motor severity, fatigue, depression and quality of life. RESULTS: 18
      patients were randomized, 6 to each group. Compared to placebo, doxepin improved
      the Insomnia Severity Index (-9 +/- 5.4 vs. -2 +/- 3.9, p = 0.03), the SCOPA
      night score (-5.2 +/- 1.5 vs. -2.3 +/- 2.8, p = 0.049), the Pittsburgh Sleep
      Quality Index-sleep disturbances subscale (-0.5 +/- 0.5 vs 0.2 +/- 0.4, p =
      0.02), and both patient and examiner-rated clinical global impression of change
      (1.7 +/- 0.8 vs. 0.5 +/- 0.8, p = 0.03 and 1.4 +/- 0.5 vs. 0.3 +/- 0.5, p =
      0.003). On secondary outcomes doxepin reduced the fatigue severity scale (p =
      0.02) and improved scores on the Montreal Cognitive Assessment (p = 0.007). Non
      pharmacological treatment reduced the Insomnia Severity Index (-7.8 +/- 3.8 vs. 
      2.0 +/- 3.9, p = 0.03), and the examiner-reported clinical global impression of
      change (p = 0.006), but was associated with decline in Parkinson Disease
      Questionnaire-39. There were no changes in other primary and secondary outcomes,
      including actigraphy outcomes. Adverse events were comparable in all groups.
      CONCLUSION: Doxepin and non-pharmacologic treatment substantially improved
      insomnia in Parkinson's disease. These potential benefits must be replicated in a
      full confirmatory randomized controlled trial.

PMID- 23561947
TI  - Improvement of freezing of gait with amantadine in a patient with oculopharyngeal
      muscular dystrophy and Parkinsonism.

PMID- 23561948
TI  - Batch and semi-continuous anaerobic digestion of food waste in a dual solid
      liquid system.
AB  - To avoid the inhibition from both of waste oil and high concentrations of
      cationic elements, anaerobic digestion of food waste in a dual solid-liquid
      (ADSL) system was examined in this present paper. Results from batch test
      indicated that a higher methane yield could be obtained in the ADSL system. The
      methane yield of food solid waste (FSW), food liquid waste (FLW) and raw food
      waste (RFW) were 643, 659 and 581 mL/g-VS, respectively. In semi-continuous
      anaerobic digestion, the optimum organic loading rates (OLR) for FSW, FLW and RFW
      were 9, 4 and 7 g-VS/L/d, respectively. The total methane production of RFW and
      ADSL systems, based on 1 kg-VS(RFW), were 405 and 460 L, respectively, indicating
      that the methane production increased by 13.6% in the ADSL system. The optimum
      C/N ratio, redistribution of metal element and lower content of waste oil in FSW
      explain the higher methane production.

PMID- 23561949
TI  - Application parameters of laccase-mediator systems for treatment of sulfonamide
      antibiotics.
AB  - This is the first study to examine the application parameters for oxidation of
      two sulfonamide antibiotics (SAs), sulfadimethoxine (SDM) and sulfamonomethoxine
      (SMM), using a novel laccase and mediators. The optimal conditions in the laccase
      mediator system (LMS) were pH 4, 50-60  degrees C, and 1 mM for 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) (ABTS); pH 4, 40-60  degrees C, and 1 mM for
      violuric acid (VLA); pH 6, 50  degrees C, and 2 mM for syringaldehyde (SIR).
      Additionally, the conditions of the 4-hydroxybenzyl alcohol (HBA) mediator were
      pH 4, 30  degrees C, and 2 mM in the oxidation of SDM; and the temperature
      increased to 60  degrees C for SMM. The laccase coupled with VLA and HBA resulted
      in the lowest toxicity of the SA solutions during processing, whereas treatments
      with ABTS and SIR resulted in higher toxicities. Furthermore, the laccase used in
      this study was stable and resistant to dialysis, thus can be reused for oxidation
      process.

PMID- 23561950
TI  - Effects of salinity on the characteristics of biomass and membrane fouling in
      membrane bioreactors.
AB  - This study investigated the effects of high salinity on the performance and
      membrane fouling of membrane bioreactor (MBR) with saline wastewater. Synthetic
      wastewaters containing 5-20 g/L salts (NaCl) were treated in identical lab-scale
      (7 L) MBRs monitoring removals of dissolved organic carbon (DOC) and ammonia.
      Increase in salt concentrations did not significantly change the removal
      efficiency of DOC in the MBRs. However, the ammonia removals decreased from 87%
      to 46% with increasing salt concentrations. PCR-DGGE analysis indicated changes
      in the microbial communities' composition due to high salinity; and the changes
      in microbial composition in turn have affected the performance of the MBRs.
      Membrane fouling was accelerated by the increased pore blocking resistance at
      higher salt concentrations. Analysis results of physicochemical and biological
      characteristics of biomass (EPS, floc size, zeta potential) verified the impacts
      of high salinity on the increased membrane fouling.

PMID- 23561951
TI  - Feasibility of anaerobic digestion from bioethanol fermentation residue.
AB  - The focus of this study was the reuse of red algal ethanol fermentation residue
      as feedstock for anaerobic digestion. Levulinic acid and formic acid, the dilute
      acid hydrolysis byproducts, inhibited methanogenesis at concentrations over 3.0
      and 0.5 g/L, respectively. However, the inhibition was overcome by increasing
      inoculum concentration. A series of batch experiments with the fermentation
      residue showed increased methane yield and productivity at higher inoculum
      concentration. The maximum methane conversion rate of 84.8% was found at 5 g
      COD/L of fermentation residue at 0.25 g COD/g VSS of food-to-microorganism (F/M)
      ratio. The red algal ethanol fermentation residue can possibly be used as a
      feedstock in anaerobic digestion at appropriate concentration and F/M ratio.

PMID- 23561953
TI  - Impact of food to microorganism (F/M) ratio and colloidal chemical oxygen demand
      on nitrification performance of a full-scale membrane bioreactor treating thin
      film transistor liquid crystal display wastewater.
AB  - This study investigated impact of food to microorganism (F/M) ratio and colloidal
      chemical oxygen demand (COD) on nitrification performance in one full-scale
      membrane bioreactor (MBR) treating monoethanolamine (MEA)/dimethyl sulfoxide
      (DMSO)-containing thin film transistor liquid crystal display (TFT-LCD)
      wastewater. Poor nitrification was observed under high organic loading and high
      colloidal COD conditions, suggesting that high F/M ratio and colloidal COD
      situations should be avoided to minimize their negative impacts on nitrification.
      According to the nonmetric multidimensional scaling (NMS) statistical analyses on
      terminal restriction fragment length polymorphism (T-RFLP) results of ammonia
      monooxygenase (amoA) gene, the occurrence of Nitrosomonas oligotropha-like
      ammonia oxidizing bacteria (AOB) was positively related to successful
      nitrification in the MBR systems, while Nitrosomonas europaea-like AOB was
      positively linked to nitrification rate, which can be attributed to the high
      influent total nitrogen condition. Furthermore, Nitrobacter- and Nitrospira-like
      nitrite oxidizing bacteria (NOB) were both abundant in the MBR systems, but the
      continuously low nitrite environment is likely to promote the growth of
      Nitrospira-like NOB.

PMID- 23561952
TI  - Optimization of dark fermentative H2 production from microalgal biomass by
      combined (acid + ultrasonic) pretreatment.
AB  - In this study, individual pretreatments (acid and ultrasonic) and a combination
      of these pretreatments were optimized to enhance the efficiency of dark
      fermentative hydrogen production (DFHP) from microalgal biomass. The experimental
      results show that the maximum H2 production performance of 42.1 mL H2/g dry cell
      weight (dcw) was predicted at 0.79% (v/w) HCl and at a specific energy input
      (SEI) of 49,600 kJ/kg dcw in the combined pretreatment, while it was limited in
      both individual pretreatments. Repeated batch testing of the predicted optimal
      conditions revealed that the combined pretreatment conditions for DFHP from
      microalgal biomass were successfully optimized by increasing the solubilization
      of the feedstock and by reducing the formation of the toxic 5
      hydroxymethylfurfural (HMF).

PMID- 23561955
TI  - Ambient temperature SNAD process treating anaerobic digester liquor of swine
      wastewater.
AB  - In present study, effluent from anaerobic digestion of swine wastewater was
      treated by the simultaneous partial nitrification, anaerobic ammonium oxidation
      and denitrification (SNAD) process using a lab scale 5L sequencing batch reactor
      (SBR) under ambient temperature. The fluctuation of anaerobic digester liquor
      quality (COD, 387 +/- 145 mg/L; TKN, 662 +/- 190 mg/L; NH4(+)-N, 519 +/- 134
      mg/L) and temperature created difficulties to develop a stable SNAD process in
      the SBR (days 1-285). Fed batch feeding strategy was adopted to have a stable
      condition in the reactor and overcome the negative effects of organic nitrogen.
      The average total nitrogen, NH4(+)-N and COD removal efficiencies in the SBR
      under steady state conditions (days 485-523) were 80%, 96% and 76%, respectively.
      The results showed that presence of organic nitrogen, mode of feeding and reactor
      temperature affects the SNAD process.

PMID- 23561954
TI  - Kinetics of transesterification of olive oil with methanol catalyzed by
      immobilized lipase derived from an isolated Burkholderia sp. strain.
AB  - This work was carried out to investigate the acyl migration phenomena which has
      been considered as the factor having significant impact on kinetics of
      transesterification of oils catalyzed by a Burkholderia lipase with 1,3
      regioselectivity. Transesterification of olive oil with methanol catalyzed by the
      immobilized lipase produces various intermediates, including 1-monoglyceride, 2
      monoglyceride, 1,2-diglyceride, and 1,3-diglyceride. Migration kinetics of fatty
      acid groups from sn-2 of 2-monoglyceride and 1,2-diglyceride to 1-monoglyceride
      and 1,3-diglyceride were investigated for the temperature range of 25-65 degrees
      C. The kinetics of transesterification of olive oil with methanol involving acyl
      migration in the presence of water was also systematically studied at 25, 40, and
      65 degrees C. Increasing temperature could increase the acyl migration rate. The
      overall biodiesel conversion was improved from 73.4% (at 25 degrees C) to 90.0%
      and 92.4% when conducting at 40 and 65 degrees C, respectively. Thermodynamics
      aspects of equilibrium state of the immobilized lipase-catalyzed
      transesterification were also discussed. 

PMID- 23561956
TI  - Nitrous oxide emission mechanisms during intermittently aerated composting of
      cattle manure.
AB  - To investigate the mechanisms of nitrous oxide (N2O) emission during intermittent
      aeration in the composting process, a laboratory scale experiment with continuous
      measurement of N2O emission was conducted with cattle manure. A low oxygen mode
      (2.5% oxygen in the inlet for 1 day), anaerobic mode (0.13% oxygen for 0.25 day),
      and aerated mode (20.5% oxygen for 2 days) were sequentially set up three times
      after 22 days of continuous aeration to replicate intermittent aeration. The
      total N2O emission was 0.26-0.35 mmol, 0.27-0.32 mmol, and 0.14-0.23 mmol during
      the low oxygen, anaerobic, and aerated modes, respectively. Denitrification was
      indicated as the main N2O emission pathway in the anaerobic and low-oxygen modes,
      while nitrification was indicated as the main pathway in the aerated mode and
      under continuous aeration. Results from this study suggest that nitrification is
      an important pathway for N2O emission as well as denitrification.

PMID- 23561957
TI  - Intermittent aeration strategy to enhance organics and nitrogen removal in
      subsurface flow constructed wetlands.
AB  - In this study, an intermittent-aerated subsurface flow constructed wetland (SFCW)
      A was set up to assess its performance in decentralized rural sewage treatment. A
      conventional SFCW B and a subsurface wastewater infiltration system (SWIS C) were
      also constructed for comparison. Alternate anaerobic and aerobic conditions were
      well developed by intermittent aeration. High removal of organic pollutants (29.3
      gm(-2) d(-1)), ammonium nitrogen (3.5 gm(-2) d(-1)) and total nitrogen (3.3 gm(
      2) d(-1)) were obtained simultaneously in SFCW A compared with SFCW B and SWIS C.
      Fluorescence in situ hybridization analysis proved that the intermittent aeration
      obviously enhanced the growth of ammonia-oxidizing bacteria (AOB) and nitrite
      oxidizing bacteria (NOB) in SFCW A. These results suggest that intermittent
      aeration strategy is reliable to enhance the performance of SFCWs in
      decentralized rural sewage treatment.

PMID- 23561958
TI  - A retrospective analysis of Salmonella serovars isolated from pigs in Great
      Britain between 1994 and 2010.
AB  - A retrospective study analysing Salmonella serovars and antimicrobial resistance
      data from pigs in Great Britain between 1994 and 2010 was performed. Data were
      obtained through scanning surveillance and compared with prevalence data from
      other livestock species as well as human data. During the study period, two
      serovars, S. Typhimurium and S. Derby, predominated in British pigs. The total
      number of Salmonella incidents has decreased steadily over the study period, from
      360 incidents per year in 1994 to 172 incidents in 2010. S. Typhimurium has been
      the most common serovar every year, but the relative percentage went down over
      the past few years. During the same time period, monophasic strains of S.
      Typhimurium have increased in numbers and were accounting for as much as 25% of
      incidents in 2010, representing the second most common serovar in British pigs in
      2010. Antimicrobial resistance data from S. Typhimurium isolates show that the
      percentage of isolates which are resistant to six or more antimicrobials has
      increased from 27.2% in 1994 to 58.3% in 2010 and that the percentage of isolates
      fully sensitive to the panel of antimicrobials tested was only 3.3% in 2010. S.
      Typhimurium isolates belonged mainly to phagetypes DT193 and U288 in 2010, and an
      increase can be seen in the number of isolates belonging to phage type DT193.
      DT104, which was the predominant phagetype during the 1990s, has gone down
      considerably and represented less than 5% of all S. Typhimurium isolates in 2010.
      Monophasic strains of S. Typhimurium belonged mainly to phagetype 193 with less
      than 20% belonging to phagetype 120. The overall trend shows that the number of
      Salmonella incidents reported from British pigs has gone down considerably over
      the 17-year study period, but that the relative percentage of monophasic strains
      of S. Typhimurium has increased significantly. This trend seems to be in line
      with observations from other European countries, where an increase of this
      serovar can be seen both in livestock and in human patients. The increasing
      percentage of Salmonella-isolates which show multi-resistance is a matter of
      concern and has to be monitored carefully in order to assess any potential risks
      this may pose to human patients.

PMID- 23561959
TI  - Efficacy and safety of autologous bone marrow-derived stem cell transplantation
      in patients with type 2 diabetes mellitus: a randomized placebo-controlled study.
AB  - There is a growing interest in cell-based therapies in T2DM as beta-cell failure
      is progressive and inexorable with the advancing duration of disease. This
      prospective, randomized, single-blinded placebo-controlled study evaluates the
      efficacy and safety of autologous bone marrow-derived stem cell transplantation
      (ABMSCT) in T2DM. Twenty-one patients with triple oral antidiabetic drug failure
      and requiring insulin >=0.4 IU per kg per day with HbA1c <7.5% were randomly
      assigned to an intervention (n = 11) and control group (n = 10) and followed for
      12 months. Patients in the intervention group received ABMSCT through a targeted
      approach, and after 12 weeks, a second dose of stem cells was administered
      through the antecubital vein after mobilization with G-CSF, while the control
      group underwent a sham procedure. The primary end point was a reduction in
      insulin requirement by >=50% from baseline while maintaining HbA1c <7%. Nine out
      of the 11 (82%) patients in the intervention group achieved the primary end
      point, whereas none of the patients in the control group did over the study
      period (p = 0.002). The insulin requirement decreased by 66.7% in the
      intervention group from 42.0 (31.0-64.0) IU per day to 14.0 (0.0-30.0) IU per day
      (p = 0.011), while in controls it decreased by 32.1% from 40.5 (31.8-44.3) IU per
      day to 27.5 (23.5-33.3) IU per day (p = 0.008) at 12 months. The reduction in
      insulin requirement was significantly more in the intervention group compared to
      controls at both 6 (p = 0.001) and 12 months (p = 0.004). There was a modest but
      nonsignificant increase in HbA1c (%) in cases from 6.9% (6.4-7.2%) to 7.1% (6.6
      7.5%) as well as in controls from 6.9% (6.2-7.0%) to 7.0% (6.9-7.5%). Ten out of
      11 (91%) patients could maintain HbA1c <7% in the intervention group, whereas 6
      out of 10 did (60%) in the control group (p = 0.167). The glucagon-stimulated C
      peptide significantly increased in treated cases compared to controls (p =
      0.036). The decrease in insulin requirement positively correlated with stimulated
      C-peptide (r = 0.8, p = 0.001). In conclusion, ABMSCT results in a significant
      decrease in the insulin dose requirement along with an improvement in the
      stimulated C-peptide levels in T2DM. However, a greater number of patients with a
      longer duration of follow-up are required to substantiate these observations.

PMID- 23561960
TI  - Endoluminal revision of gastric bypass for weight regain--a systematic review.
AB  - BACKGROUND: Weight recidivism after Roux-en-Y gastric bypass (RYGB) is a
      challenging problem for patients and bariatric surgeons alike. Traditional
      operative strategies to combat weight regain are technically challenging and
      associated with a high morbidity rate. Endoluminal interventions are thus an
      attractive alternative that may offer a good combination of results coupled with
      lower periprocedure risk that might one day provide a solution to this
      increasingly prevalent problem. The purpose of this article is to systematically
      review the available literature on endoluminal procedures used to address weight
      regain after RYGB, with specific attention to the safety profile, efficacy, cost,
      and current availability. This review focuses only on endoluminal procedures that
      are performed for weight regain after RYGB, as opposed to primary endoluminal
      obesity procedures. METHODS: This study was a retrospective review. RESULTS:
      Several methods of endoluminal intervention for weight regain are reviewed,
      ranging from injection of inert substances to suturing and clipping devices. The
      literature review shows the procedures on the whole to be well tolerated with
      limited efficacy. The majority of the literature is limited to small case series.
      Most of the reviewed devices are no longer commercially available. CONCLUSIONS:
      Endoluminal therapy represents an intriguing strategy for weight regain after
      RYGB. However, the current and future technologies must be rigorously studied and
      improved such that they offer durable, repeatable, cost-effective solutions.

PMID- 23561961
TI  - Remission of female sexual dysfunction in morbidly obese female patients with the
      Scopinaro procedure.
AB  - BACKGROUND: The prevalence of obesity has increased in Spain in recent years.
      Obese women are at increased risk for sexual dysfunction, and important remission
      of this condition has been previously reported with bariatric surgery.
      OBJECTIVES: The major aim of this study was to assess the effects of the
      Scopinaro biliopancreatic diversion on female sexual dysfunction (FSD) using a
      validated Female Sexual Function Index (FSFI). METHODS: Eighty sexually active
      women with morbid obesity and with FSD underwent surgery. All patients completed
      the FSFI before surgery, as well as 6 and 12 months after surgery. The FSFI
      evaluates the sexual function using 6 items: desire, arousal, lubrication,
      orgasm, satisfaction, and pain. We used a<26.5 cut-point to assess the presence
      of FSD. This cut-point is used as a standard for the investigation. RESULTS:
      Before surgery, all patients had FSD (mean 19.9+/-1.6). Six months after surgery,
      the FSD improved (mean 25.4+/-4.1; P<.001), and 12 months after surgery FSD
      resolved in most of the patients (mean 30.4+/-3.5; P<.001). All of the parameters
      evaluated by the FSFI (P<.001) improved significantly in all patients.
      CONCLUSION: FSD improved significantly 6 months after biliopancreatic diversion
      among obese women with preoperative sexual dysfunction and continued improving up
      to 12 months later.

PMID- 23561964
TI  - Introduction for the IAP/APC symposium papers.

PMID- 23561962
TI  - Is selection bias toward super obese patients in the rationing of metabolic
      surgery justified?--A pilot study from the United Kingdom.
AB  - BACKGROUND: Recent evidence suggests that National Health Service (NHS) rationing
      of bariatric surgery is biased toward super-obese patients without scientific
      basis. The aim of this study was to compare health, quality of life, and
      employment outcomes in morbidly obese (MO) versus super-obese (SO) patients after
      laparoscopic Roux-en-Y gastric bypass (LRYGB) to provide a basis for rationing.
      METHODS: Consecutive patients undergoing LRYGB from January 2008-September 2009,
      with baseline body mass index (BMI)<45 kg/m(2) (MO) and BMI>60 kg/m(2) (SO) were
      identified from a prospective database. Seventy-six eligible patients were
      invited to complete a questionnaire comprising BAROS (bariatric analysis and
      reporting outcome system), EQ-5D (EuroQol-5D), EQVAS (Euro-QoL visual analog
      score), and employment status preoperatively and postoperatively. Anthropometric,
      demographic, and clinical data were recorded. RESULTS: Fifty-one patients
      responded: 23 MO and 28 SO. Groups were matched for demographic characteristics
      and co-morbidities. The MO group had significantly higher percentage excess
      weight loss (%EWL) (82% versus 53%; t test: P<.001) and mean BAROS score (5.47
      versus 4.21; t test: P = .025) than the SO group. EQ-5D improved significantly
      for both groups in 3 domains (self care, anxiety/depression, and
      pain/discomfort); there was no significant difference in improvement between
      groups. EQVAS was significantly higher for the MO group (90 versus 70; Mann
      Whitney U: P = .001). Employment status changed for 8 patients postoperatively,
      but there was no significant difference between groups. CONCLUSION: These results
      suggest that MO patients appear to benefit more than SO patients from LRYGB and
      yet seem to be disadvantaged in some NHS Trusts in the United Kingdom for access
      to bariatric surgery. This study provides a baseline framework for further
      research to generate evidence for more scientific rationing of bariatric surgery.

PMID- 23561965
TI  - Pancreatic stellate cells--multi-functional cells in the pancreas.
AB  - There is accumulating evidence that activated pancreatic stellate cells (PSCs)
      play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic
      cancer. In addition, we have seen great progress in our understanding of the cell
      biology of PSCs and the interactions between PSCs and other cell types in the
      pancreas. In response to pancreatic injury or inflammation, quiescent PSCs are
      activated to myofibroblast-like cells. Recent studies have shown that the
      activation of intracellular signaling pathways such as mitogen-activated protein
      kinases plays a role in the activation of PSCs. microRNAs might also play a role,
      because the microRNA expression profiles are dramatically altered in the process
      of activation. In addition to producing extracellular matrix components such as
      type I collagen, PSCs have a wide variety of cell functions related to local
      immunity, inflammation, angiogenesis, and exocrine and endocrine functions in the
      pancreas. From this point of view, the interactions between PSCs and other cell
      types such as pancreatic exocrine cells, endocrine cells, and cancer cells have
      attracted increasing attention of researchers. PSCs might regulate exocrine
      functions in the pancreas through the cholecystokinin-induced release of
      acetylcholine. PSCs induce apoptosis and decrease insulin expression in beta
      cells, suggesting a novel mechanism of diabetes in diseased pancreas. PSCs
      promote the progression of pancreatic cancer by multiple mechanisms. Recent
      studies have shown that PSCs induce epithelial-mesenchymal transition and enhance
      the stem-cell like features of pancreatic cancer cells. In conclusion, PSCs
      should now be recognized as not only profibrogenic cells but as multi-functional
      cells in the pancreas.

PMID- 23561966
TI  - The role of pancreatic stellate cells in pancreatic cancer.
AB  - Since conventional and targeted therapies aiming at cancer cells have largely
      failed to prolong survival in pancreatic cancer, targeting the infrastructure of
      the tumor, hence its stroma is a novel strategy. It is believed that fibrotic and
      hypovascular stroma forms a barrier around cancer cells, hindering effective
      delivery of chemotherapy. Theoretically, antifibrotic therapy should reduce the
      compactness of the stroma and reduce the interstitial pressure, allowing better
      delivery of chemotherapy. This approach has worked successfully in a genetically
      engineered mouse model but failed in humans, paradoxically increasing mortality
      in the treatment arm. Normally, stromal cells deposit extracellular matrix as an
      innate defensive reaction to form a barrier between what is harmful and the rest
      of the body. Despite the significant amount of in vitro data suggesting the pro
      tumorigenic roles of activated stellate cells, there is no reason to believe that
      stellate cells around genetically mutated cells are from the beginning there to
      support carcinogenesis. Such a stromal activation is also observed around PanIN
      lesions (which harbor genetically mutated cells) in chronic pancreatitis, where
      no cancer develops. In pancreatic cancer, the selection pressure created by the
      fibrotic and hypoxic stroma eventually leads to the evolution of more aggressive
      clones, indirectly contributing to the aggressiveness of the tumor. Here, the
      main problem is the late diagnosis of pancreatic cancer, which gives cancer cells
      enough time for malignant evolution. Therefore, applying antifibrotic therapy at
      a late stage can be counterproductive. It may increase delivery of chemotherapy,
      but also lead to the escape of cancer cells.

PMID- 23561967
TI  - Stem cells & pancreatic cancer.
AB  - It is now well established that human pancreatic ductal adenocarcinoma (PDAC)
      contains a subset of cells with self-renewal capabilities and subsequent
      exclusive in vivo tumorigenic capacity as assessed by limiting dilution
      tumorigenic transplantation assays into immunodeficient mice. These cells are
      considered pancreatic cancer stem cells (CSCs) and are able to form tumors
      indistinguishable from parental ones. Furthermore they display strong
      chemotherapy resistance and are implicated in tumor relapses and metastatic
      spread. Important next steps for advancing the field of pancreatic CSC research
      include the identification and characterization of CSCs in the unperturbed in
      vivo setting. This has been achieved just recently for other solid tumors such as
      glioblastoma using clonal analysis after lineage tracing in mice [1]. In vivo
      imaging of CSCs during tumor development should not only provide new insights
      into the in vivo features of CSCs, but also help to further unravel the influence
      of the stroma on CSC biology. Comprehensive studies of the tumor heterogeneity
      with respect to the coexistence of different clones potentially generated by
      distinct population of CSCs that are evolving by stochastic cell fate decisions
      may actually unite the CSC concept and the model of clonal evolution for
      pancreatic cancer. Eventually, the design of specific therapies against CSCs
      should open new alleys to improve survival of patients with PDAC. Combined
      therapies targeting CSCs and their progenies as well as the supportive stroma may
      represent the most promising approach for the future treatment of patients with
      PDAC.

PMID- 23561968
TI  - Epithelial to mesenchymal transition and the generation of stem-like cells in
      pancreatic cancer.
AB  - An epithelial-to-mesenchymal transition (EMT) is thought to be an important
      process in the acquisition of capabilities required for metastasis. Until
      recently, studies of EMT involved mostly in vitro assays and transplantation
      experiments of cancer cells that overexpressed known EMT drivers. While valuable,
      these studies do not allow us to conclude if an EMT sustained under "physiologic
      conditions" within the tumor microenvironment leads to the myriad changes in
      phenotype observed in vitro. Here we review our recently published work using a
      lineage labeled genetically engineered mouse model of pancreatic ductal
      adenocarcinoma to characterize cells that have sustained an EMT in vivo.

PMID- 23561969
TI  - Patients with acute pancreatitis complicated by organ dysfunction show abnormal
      peripheral blood polymorphonuclear leukocyte signaling.
AB  - BACKGROUND/OBJECTIVES: Circulating polymorphonuclear leukocytes (PMNLs) may
      contribute to development of organ dysfunction in acute pancreatitis (AP). We
      outlined aberrations in PMNL signaling profiles in patients with AP complicated
      by organ dysfunction and immune suppression. METHODS: Study comprised 13 patients
      treated at intensive care unit due to severe AP complicated by vital organ
      dysfunction. Mean proportion (SEM) of HLA-DR-positive monocytes was 55.0% (4.1%).
      13 healthy volunteers served as reference subjects. Phosphorylation of PMNL
      NFkappaB, p38, ERK1/2 and STAT3, -5 and -6 was determined using whole blood flow
      cytometry. Transmigration of PMNLs was studied using endothelial EA-HY cell
      monolayer. RESULTS: Proportions of NFkappaB phosphorylation-positive PMNLs were
      lower in the patients' than in reference subjects' blood samples supplemented
      with tumor necrosis factor. p38 phosphorylation was normal while ERK1/2
      phosphorylation was decreased. STAT3 was constitutively activated in five
      patients. Proportion of patients' pSTAT6-positive cells was normal while
      fluorescence intensity was decreased. STAT5 phosphorylation was normal.
      Transmigration of patients' PMNLs was increased. CONCLUSIONS: In patients with AP
      complicated by organ dysfunction proportion of pNFkappaB-positive PMNLs is
      decreased. This impairs patients' defense mechanisms against infection. Despite
      immune suppression, PMNL transmigration was increased and p38 phosphorylation
      capacity was not depressed, which may contribute to end organ inflammation and
      dysfunction.

PMID- 23561970
TI  - Protective effects of edaravone on experimental chronic pancreatitis induced by
      dibutyltin dichloride in rats.
AB  - BACKGROUND/AIMS: To investigate the effects of edaravone, a potent free radical
      scavenger, on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and
      pancreatic fibrosis. METHODS: Male Sprague-Dawley rats were randomly divided into
      four groups (n = 16 each): control, DBTC, DBTC + edaravone, and control +
      edaravone. Edaravone or normal saline at a daily dose of 6 mg/kg body weight was
      given intraperitoneally from day 5 to day 28 after DBTC administration. On days
      14 and 28, the rats were evaluated morphologically and biochemically. The
      expression of cytokines in pancreas TGF-beta, IL-6 and TNF<alpha> was detected
      using RT-PCR. The activation of nuclear factor (NF)-kappaB in pancreatic tissue
      was evaluated by immunostaining and western-blot for NF-kappaB p65. alpha-smooth
      muscle actin (alpha-SMA) expression was also evaluated by immunostaining and
      western-blot to investigate the activation of pancreatic stellate cells (PSCs).
      RESULT: Edaravone treatment improved the rats' body weight (p < 0.01) and feed
      intake levels (p < 0.05), improved the histological scores and alleviated the
      fibrosis of pancreas samples (p < 0.05), as well as markedly increased superoxide
      dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in
      pancreatic tissue (p < 0.01 for both). The expression of cytokines TGF-beta, IL-6
      and TNF<alpha> in pancreas of DBTC group was also down-regulated by edaravone
      after treatment. Edaravone inhibited the activation of NF-kappaB and PSCs and
      exhibited protective effects on pancreatic tissue damage in CP. CONCLUSIONS: This
      antioxidant may be a promising therapeutic intervention for human CP.

PMID- 23561971
TI  - A 51-week, open-label clinical trial in India to assess the efficacy and safety
      of pancreatin 40000 enteric-coated minimicrospheres in patients with pancreatic
      exocrine insufficiency due to chronic pancreatitis.
AB  - BACKGROUND/OBJECTIVES: To assess the efficacy and safety of pancreatin
      (pancrelipase) enteric-coated minimicrospheres (MMS) over a one-year period in
      patients with pancreatic exocrine insufficiency (PEI) due to chronic pancreatitis
      (CP). METHODS: This was a 51-week, open-label extension (OLE) of a one-week,
      multicenter, double-blind, randomized, placebo-controlled trial in India that
      enrolled patients >=18 years of age with confirmed PEI due to CP. Patients
      received pancreatin (Creon((r)) 40000 MMSTM) at a dose of 80,000 Ph. Eur. lipase
      units with each of three main meals/day and 40,000 with each of up to three
      snacks/day. RESULTS: Of 61 patients entering the OLE, 48 completed treatment
      (nine were lost to follow up, two withdrew consent, one discontinued due to
      adverse event [acute exacerbation of CP], one protocol violation). There were
      significant improvements from baseline to end of OLE in mean +/- SD coefficient
      of fat absorption (CFA: 22.7 +/- 12.2%), coefficient of nitrogen absorption (CNA:
      6.5 +/- 7.9%), body weight (4.9 +/- 4.9 kg), BMI (1.9 +/- 1.9 kg/m(2)), and most
      nutritional laboratory parameters tested (p <= 0.001). Mean daily stool frequency
      was reduced from 2.8 to 1.6 (p < 0.001). Improvements in clinical symptoms,
      clinical global impression of disease symptoms, and quality of life were also
      observed. Treatment-emergent adverse events (TEAEs) were observed in 64% of
      patients overall. Only 13% of patients experienced TEAEs judged treatment
      related. CONCLUSIONS: In patients with PEI due to CP, treatment with pancreatin
      for one year was associated with significant improvements in fat absorption,
      nitrogen absorption, and nutritional parameters, improvements in clinical
      symptoms, and a favorable safety and tolerability profile.

PMID- 23561972
TI  - Nicotinamide prohibits proliferation and enhances chemosensitivity of pancreatic
      cancer cells through deregulating SIRT1 and Ras/Akt pathways.
AB  - BACKGROUND: Nicotinamide (NAM), the precursor for the synthesis of NAD(+) and
      also an inhibitor of SIRT1, has been discovered to inhibit some types of cancer.
      However, little is known about the effects of NAM on pancreatic cancer cells.
      Since previous research showed that SIRT1 and K-Ras/Akt signaling acted as a
      promoter in tumorigenesis of pancreatic cancer, our present research set out to
      explore whether NAM inhibits proliferation and facilitates chemosensitivity in
      pancreatic cancer cells as well as the potential mechanisms involving SIRT1 and K
      Ras/Akt pathway. METHODS: Cell viability was assessed by MTT assay, and apoptosis
      and cell cycle were measured by flow cytometry. Cell invasive ability was
      evaluated by matrigel invasion assays. The activity of SIRT1 was measured by the
      Fluor de Lys deacetylation assay. Expression levels of SIRT1, K-Ras, Phosphated
      Akt (P-Akt, Ser-473) and Akt were measured using western blot. In vivo tumor
      growth was performed in pancreatic cancer cells xenografts. RESULTS: NAM
      inhibited the proliferation of pancreatic cancer cells in a dose-dependent
      manner, and significantly induced apoptosis and cell cycle arrest in G2/M phase.
      Moreover, NAM obviously restrained cell invasive ability and increased the
      chemosensitivity. NAM significantly inhibited the activity of SIRT1 and decreased
      expression of SIRT1, K-Ras and P-Akt. Further, NAM prohibited proliferation and
      enhanced GEM antitumor activity in vivo. CONCLUSIONS: Our results implied that
      NAM might be a potential therapeutic agent for human pancreatic cancer treatment
      through downregulating SIRT1, K-Ras and P-Akt expression.

PMID- 23561973
TI  - Association between hepatitis B or hepatitis C virus infection and risk of
      pancreatic adenocarcinoma development: a systematic review and meta-analysis.
AB  - BACKGROUND: Pancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor
      prognosis. To date, PAC causes are still largely unknown. Antigens and
      replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus
      were detected in different extra-hepatic tissues, including pancreas. OBJECTIVE:
      a systematic review and meta-analysis of epidemiological studies assessing PAC
      risk in patients with HBV/HCV chronic infections. METHODS: In September 2012, we
      extracted the articles published in Medline, Embase and the Cochrane Library,
      using the following search terms: "chronic HBV" and "HCV", "hepatitis", "PAC",
      "risk factors", "epidemiology". Only case/control (C/C),
      prospective/retrospective cohort studies (PCS/RCS) written in English were
      collected. RESULTS: four hospital-based C/C studies and one PCS, in HBV-infected
      patients and two hospital-based C/C studies and one RCS in HCV-infected subjects
      met inclusion criteria. In these studies HBsAg positivity enhanced significantly
      PAC risk (RR = 1.18, 95% CI:1.04-1.33), whereas HBeAg positivity (RR = 1.31, 95%
      CI:0.85-2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR
      = 1.12, 95% CI:0.78-1.59) and HBsAg negative/HBcAb positive/HBsAb negative
      pattern (RR = 1.30, 95% CI:0.93-1.84) did not. Relationship between PAC risk and
      anti-HCV positivity was not significant, although it reached a borderline value
      (RR = 1.160, 95% CI:0.99-1.3). CONCLUSIONS: HBV/HCV infection may represent a
      risk factor for PAC, but the small number of available researches, involving
      mainly populations of Asian ethnicity and the substantial variation between
      different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and
      genotypes are limiting factors to present meta-analysis.

PMID- 23561974
TI  - A novel scoring system for arterial invasion of pancreatic body and tail cancer
      based on multidetector row computed tomography and biomarkers.
AB  - BACKGROUND/OBJECTIVES: The absence of major-vessel involvement is a crucial
      factor in the resectability and prognosis of pancreatic cancer. However, arterial
      invasion cannot be evaluated adequately using imaging findings alone. We
      therefore developed a scoring system to assess arterial invasion by pancreatic
      adenocarcinoma using multidetector row computed tomography (MDCT) and serum tumor
      markers. METHODS: Twenty patients who underwent distal pancreatectomy and
      splenectomy for pancreatic adenocarcinoma were examined retrospectively using 4-,
      16- or 64-row MDCT and serum tumor markers. Splenic arterial invasion was
      evaluated in terms of length of tumor contact, circumferential involvement (<180
      degrees  or >=180 degrees ) and deformity of vascular diameter. Preoperative
      expression of carbohydrate antigen 19-9 (CA19-9), DUPAN-2 and S-Pancreas-1
      antigen (SPan-1) were also evaluated. The presence or absence of arterial
      invasion was confirmed histopathologically in all 20 cases. RESULTS: In 11 of 20
      cases invasion into splenic arteries was observed histopathologically, mostly
      involving the external elastic lamina and periarterial nerves. Sensitivity,
      specificity and accuracy were 100%, 88.9% and 95%, respectively, for length of
      tumor contact (<16 mm or >=16 mm), 90.9%, 77.8% and 85% for circumferential
      involvement (<180 degrees  or >=180 degrees ), and 100%, 66.7% and 85% for
      deformity of vascular diameter. Furthermore, the sensitivity, specificity and
      accuracy were all increased to 100% when tumor markers were included in the
      score. CONCLUSIONS: MDCT is a useful technique for diagnosing arterial invasion
      of pancreatic body and tail cancer, even in comparison with pathological
      examination; however, this new scoring system can be further complemented and
      made more reliable by measurements of serous tumor markers.

PMID- 23561975
TI  - Modified duodenum-preserving pancreas head resection for low-grade malignant
      lesion in the pancreatic head.
AB  - BACKGROUND/OBJECTIVES: Our institution has utilized a duodenum-preserving
      pancreas head resection (DPPHR) procedure for management of low-grade malignant
      lesions within the head of the pancreas, but this has resulted in a higher rate
      of postoperative complications, including pancreatic fistula and ischemic bile
      duct injury. To avoid these complications we recently modified DPPHR to resect
      all the parenchyma around the pancreatic head and to preserve the epicholedochal
      plexus around the bile duct. The goal of this study was to investigate outcomes
      with postoperative complications and disease control following this modified
      procedure. METHODS: Twenty-one consecutive patients underwent DPPHR between 1994
      and 2011. Patients were retrospectively classified into one of two groups: the
      conventional DPPHR group (cDPPHR) or the modified DPPHR group (mDPPHR).
      Perioperative factors and postoperative complications were compared between these
      two groups. RESULTS: The median age of the 21 patients was 61 (23-77) years, and
      the median follow-up period was 51 months. Intra-operational blood loss was
      significantly smaller and duration of hospital stay was significantly shorter in
      the mDPPHR group than in the cDPPHR group, respectively. The rate of pancreatic
      fistula was markedly lower in the mDPPHR group (2/13; 15%) than in the cDPPHR
      group (7/8; 88%) (P = 0.0022). For neoplastic lesions, the surgical margin was
      negative in all cases, and local recurrence has not occurred in either group.
      CONCLUSIONS: For selected patients, modified DPPHR may provide clinical benefits
      in terms of less complications associated with shorter hospital stay.

PMID- 23561976
TI  - Post-operative morbidity and mortality in pancreatic surgery. The role of
      surgical Apgar score.
AB  - BACKGROUND: Morbidity and mortality rates after pancreatic resection still remain
      high. The surgical Apgar score (SAS) has been recently introduced as predictive
      value of perioperative outcomes after pancreatic surgery. Aim of the study was to
      detect significant parameters affecting post-operative outcomes in pancreatic
      surgery, and to evaluate the role of SAS in predicting morbidity, pancreatic
      fistulas and mortality. MATERIALS AND METHODS: Data were collected from 143
      patients who had undergone pancreatic resection for pancreatic and periampullary
      adenocarcinoma. Pre-operative and intra-operative parameters were statistically
      analyzed to evaluate their potential prognostic effects. RESULTS: A low SAS (p =
      0.001), hypo-albuminemia (p = 0.003), and the need for blood transfusions (p =
      0.05) were significant independent predictors of postoperative morbidity. The SAS
      was demonstrated to significantly predict major complications (p = 0.001)
      surgical site infections (p = 0.001) and mortality (p = 0.001). CONCLUSION: The
      SAS provides a simple, immediate, and objective means of measuring patient
      outcomes in surgery. This score should be used to identify patients at high risk
      of major complications and death after pancreatic surgery and may be useful to
      optimize the use of postoperative critical care beds and hospital resources.

PMID- 23561977
TI  - Improved survival and quality of life in patients undergoing R1 pancreatic
      resection compared to patients with locally advanced unresectable pancreatic
      adenocarcinoma.
AB  - OBJECTIVE: To prospectively record the clinical consequences of R1 resection of
      pancreatic adenocarcinoma compared to patients with locally advanced tumours not
      undergoing surgery. BACKGROUND: Surgery is the only potentially curative
      treatment of pancreatic cancer, and postoperative safety is increasing. The rate
      of R1 resections might also increase unintentionally as surgical procedures with
      curative goal become more comprehensive, and the clinical outcome requires
      further prospective evaluation. MATERIAL AND METHODS: Prospective observational
      cohort study from October 2008 to December 2010. Outcome after R1 resection
      (group 1, surgery, n = 32) and conservative palliative chemoradiation/endoscopy
      (group 2, no surgery, n = 56) is compared with survival and longitudinal patient
      reported quality of life (QoL) as endpoints. QoL was assessed by the Edmonton
      Symptom Assessment System (ESAS). RESULTS: Demographic characteristics and tumour
      diameters were similar in both groups: 38.0 (31.3, 49.8) mm in group 1 versus
      44.0 (39.6, 49.1) mm in group 2 (p = 0.18). Perioperative morbidity was 25% with
      no mortality. Disease-specific survival was 18.0 (14.5, 23.8) months in group 1
      versus 8.1 (4.8, 10.1) months in group 2 (p < 0.0001). Overall survival was 11
      (7.8, 14.4) months. Reduction in fatigue was significantly improved in the
      surgery group 6, 12, and 19 weeks after baseline, whereas reduction in global
      health was significantly better in group 2. CONCLUSION: Radical removal (R0
      resection) is the primary aim of surgery, but also R1 resection seems to improve
      survival and QoL, compared to outcome in patients with locally advanced tumours
      not undergoing surgery.

PMID- 23561978
TI  - Case report: recurrent acute pancreatitis secondary to papillary somatostatinoma-
      a new association.
AB  - Acute pancreatitis may rarely be caused by papillary mass lesions such as
      adenocarcinomas and neuroendocrine tumours. Occasionally these papillary lesions
      may cause recurrent episodes of acute pancreatitis and patients presenting in
      this way require further pancreatic investigation. We believe this to be the
      first reported case of a duodenal papillary somatostatinoma causing recurrent
      acute pancreatitis. The patient was investigated with multiple imaging
      modalities, both at endoscopy and with more traditional radiology, and treated
      with resection by Whipple's pancreaticoduodenectomy. If diagnosed early in the
      absence of distant metastases the prognosis of papillary somatostatinoma with
      tumour resection is excellent.

PMID- 23561979
TI  - Acute pancreatitis caused by bortezomib.
AB  - Drug-induced pancreatitis has been reported rarely. Bortezomib is a selective and
      reversible proteasome inhibitor used for the treatment of patients with multiple
      myeloma (MM). Recently, one case report about acute pancreatitis (AP) caused by
      bortezomib was published in the international literature. Herein we report a case
      of AP in a 67-year-old male on bortezomib therapy. On the fourth day after the
      first administration of bortezomib, the patient admitted to the hospital with
      symptoms of AP. The common etiological factors for AP were all excluded. Than the
      patient was diagnosed as bortezomib-induced pancreatitis.

PMID- 23561980
TI  - The Lancet journals welcome a new open access policy.

PMID- 23561981
TI  - Sweet liking in patients with Parkinson's disease.
AB  - Pleasant tastes and odors are considered phylogenetically old natural rewards and
      their hedonic evaluation is regarded as a good indicator of the reward system
      function. The primary aim of the present study was to compare pleasantness
      ratings of sucrose solutions (1-30%, w/w) and sweet liking/disliking status in 20
      patients with Parkinson's disease (PD) and in 20 age-matched healthy controls. In
      addition, basic sensory aspects of gustatory (intensity ratings,
      electrogustometric thresholds) and olfactory function (identification abilities
      in the Sniffin' Stick test) were assessed in both groups. The number of odors
      rated as pleasant, unpleasant, and neutral was also compared. As expected, the PD
      patients showed a significant impairment in olfactory identification abilities.
      There were no differences between the PD patients and controls in
      electrogustometric thresholds. Rated intensity of higher sucrose concentrations
      did not differ between the groups. The PD patients tended to rate water taste as
      more intense in comparison with the controls. Pleasantness ratings of sucrose
      solutions, the proportion of subjects rating 30% sucrose as the most pleasant
      (sweet likers), and the number of odors rated as pleasant did not differ between
      the study groups. The present results suggest that PD does not lead to any
      obvious alterations in pleasantness ratings of chemosensory stimuli. The study
      requires replication in larger samples.

PMID- 23561982
TI  - Cognitive slowing in Parkinson's disease is related to frontostriatal
      dopaminergic dysfunction.
AB  - BACKGROUND: Frontostriatal and cognitive dysfunctions in Parkinson's disease (PD)
      are hypothesized to be linked predominately to dopaminergic dysfunction within
      neural networks linking dorsal striatum to dorsolateral prefrontal cortex.
      METHODS: The authors evaluated the relationship between frontostriatal
      dopaminergic function and cognitive performance, especially cognitive processing
      speed by performing [(18)F]fluorodopa PET and computerized tests of automatic and
      controlled cognitive processing speed (CogniSpeed) in 23 newly diagnosed and
      unmedicated PD patients and 14 controls. RESULTS: PD patients were slower than
      the controls in all the CogniSpeed measures studied. The Fdopa uptake in caudate
      nucleus correlated negatively with slowing on all the tests. Slower performance
      in relatively automatic processes measured by choice reaction tasks as well as in
      more controlled processes measured by a calculation task was related to reduced
      Fdopa uptake in the anterior cingulate gyrus. The reduced dopaminergic function
      in the thalamus was associated with the slower performance in the subtraction
      test. CONCLUSION: Our study indicates that dopaminergic dysfunction within neural
      networks linking striatum to prefrontal cortex is involved in the slowing of both
      automatic and controlled cognitive processing in PD patients.

PMID- 23561983
TI  - Raising the pressure on hypertension.

PMID- 23561984
TI  - Indigenous health in Australia: unacceptable differences remain.

PMID- 23561985
TI  - Banking on the BRICS for health?

PMID- 23561986
TI  - Maternal mortality and morbidity: a human rights imperative.

PMID- 23561987
TI  - Expression of concern--effect of tesofensine on bodyweight loss, body
      composition, and quality of life in obese patients: a randomised, double-blind,
      placebo-controlled trial.

PMID- 23561989
TI  - Duncan Selbie: the new face of public health in England.

PMID- 23561990
TI  - Falls in older people in long-term care.

PMID- 23561991
TI  - The world's neglect of the Syrian humanitarian and medical crises.

PMID- 23561992
TI  - Falls in older people in long-term care.

PMID- 23561993
TI  - Falls in older people in long-term care--authors' reply.

PMID- 23561994
TI  - Discrimination reported by people with major depressive disorder.

PMID- 23561995
TI  - Discrimination reported by people with major depressive disorder.

PMID- 23561996
TI  - Discrimination reported by people with major depressive disorder--authors' reply.

PMID- 23561997
TI  - Lipid-lowering treatment for homozygous familial hypercholesterolaemia.

PMID- 23561998
TI  - Lipid-lowering treatment for homozygous familial hypercholesterolaemia--authors'
      reply.

PMID- 23561999
TI  - Turning a blind eye to deferasirox's toxicity?

PMID- 23562000
TI  - Rapid research education for medical science students.

PMID- 23562001
TI  - An unusual case of cystic interstitial lung disease.

PMID- 23562002
TI  - Obstetrics and gynecology practices and patient insurance type.
AB  - BACKGROUND: Despite research on health disparities based on insurance status,
      little is known about the differences in practice patterns among physicians who
      cater to privately and non-privately insured patients. The aim of this study was
      to assess how obstetrician-gynecologists (ob-gyns) who primarily see patients
      with private insurance differ from those who see mainly uninsured or publicly
      insured patients. This could be informative of the needs of these two groups of
      physicians and patients. METHODS: A questionnaire was mailed or emailed to 1,000
      members of the American College of Obstetricians and Gynecologists, 600 of whom
      participate in the Collaborative Ambulatory Research Network. FINDINGS: A 56.4%
      response rate was obtained. Of the valid responders, the 335 reported providing
      care to a majority of patients with private insurance ("private group") and the
      105 reported providing care to mostly publicly insured or uninsured patients
      ("non-private group") were included in our analyses. Differences between groups
      included that the private group was more likely to see patients before their
      becoming pregnant and spent more time on well-woman care. The private group was
      more likely to see patients who are White, Asian, or between the ages of 45 and
      64. The non-private group was more likely to see Hispanic patients and those
      under age 18. CONCLUSION: Results reveal that ob-gyns who see mostly privately
      insured patients have different clinical experiences than those who see mainly
      uninsured or publicly insured patients in terms of patient characteristics,
      preconception care, distribution of time on activities, and the of likelihood
      performing certain procedures and screening tests.

PMID- 23562003
TI  - Diffusion weighted MRI by spatiotemporal encoding: analytical description and in
      vivo validations.
AB  - Diffusion-weighted (DW) MRI is a powerful modality for studying microstructure in
      normal and pathological tissues. The accuracy derived from DW MRI depends on the
      acquisition of quality images, and on a precise assessment of the b-values
      involved. Conventional DW MRI tends to be of limited use in regions suffering
      from large magnetic field or chemical shift heterogeneities, which severely
      distort the MR images. In this study we propose novel sequences based on SPatio
      temporal ENcoding (SPEN), which overcome such shortcomings owing to SPEN's
      inherent robustness to offsets. SPEN, however, relies on the simultaneous
      application of gradients and radiofrequency-swept pulses, which may impart
      different diffusion weightings along the spatial axes. These will be further
      complicated in DW measurements by the diffusion-sensitizing gradients, and will
      in general lead to complex, spatially-dependent b-values. This study presents a
      formalism for analyzing these diffusion-weighted SPEN (dSPEN) data, which takes
      into account the concomitant effects of adiabatic pulses, of the imaging as well
      as diffusion gradients, and of the cross-terms between them. These analytical b
      values derivations are subject to experimental validations in phantom systems and
      ex vivo spinal cords. Excellent agreement is found between the theoretical
      predictions and these dSPEN experiments. The ensuing methodology is then
      demonstrated by in vivo mapping of diffusion in human breast - organs where
      conventional k-space DW acquisition methods are challenged by both field and
      chemical shift heterogeneities. These studies demonstrate the increased
      robustness of dSPEN vis-a-vis comparable DW echo planar imaging, and demonstrate
      the value of this new methodology for medium- or high-field diffusion
      measurements in heterogeneous systems.

PMID- 23562004
TI  - Serum protein profile of Crohn's disease treated with infliximab.
AB  - The infliximab (IFX) has dramatically improved the treatment of Crohn's disease
      (CD). However, the need for predictive factors, indicative of patients' response
      to IFX, has yet to be met. In the current study, proteomics technologies were
      employed in order to monitor for differences in protein expression in a cohort of
      patients following IFX administration, aiming at identifying a panel of candidate
      protein biomarkers of CD, symptomatic of response to treatment. We enrolled 18
      patients, who either had achieved clinical and serological remission (Rm, n=6),
      or response (Rs, n=6) and/or were PNRs (n=6), to IFX. Serum samples were
      subjected to two-dimensional Gel Electrophoresis. Following evaluation of
      densitometrical data, protein spots exhibiting differential expression among the
      groups, were further characterized by MALDI-TOF-MS. Identified proteins where
      evaluated by immunoblot analysis while functional network association was carried
      out to asses significance. Proteins apolipoprotein A-I (APOA1), apolipoprotein E
      (APOE), complement C4-B (CO4B), plasminogen (PLMN), serotransferrin (TRFE), beta
      2-glycoprotein 1 (APOH), and clusterin (CLUS) were found to be up-regulated in
      the PNR and Rs groups whereas their levels displayed no changes in the Rm group
      when compared to baseline samples. Additionally, leucine-rich alpha-2
      glycoprotein (A2GL), vitamin D-binding protein (VTDB), alpha-1B-glycoprotein
      (A1BG) and complement C1r subcomponent (C1R) were significantly increased in the
      serum of the Rm group. Through the incorporation of proteomics technologies,
      novel serum marker-molecules demonstrating high sensitivity and specificity are
      introduced, hence offering an innovative approach regarding the evaluation of CD
      patients' response to IFX therapy. 

PMID- 23562005
TI  - Inhibition of glycine transporter-I as a novel mechanism for the treatment of
      depression.
AB  - BACKGROUND: Antidepressants, aiming at monoaminergic neurotransmission, exhibit
      delayed onset of action, limited efficacy, and poor compliance. Glutamatergic
      neurotransmission is involved in depression. However, it is unclear whether
      enhancement of the N-methyl-D-aspartate (NMDA) subtype glutamate receptor can be
      a treatment for depression. METHODS: We studied sarcosine, a glycine transporter
      I inhibitor that potentiates NMDA function, in animal models and in depressed
      patients. We investigated its effects in forced swim test, tail suspension test,
      elevated plus maze test, novelty-suppressed feeding test, and chronic
      unpredictable stress test in rats and conducted a 6-week randomized, double
      blinded, citalopram-controlled trial in 40 patients with major depressive
      disorder. Clinical efficacy and side effects were assessed biweekly, with the
      main outcomes of Hamilton Depression Rating Scale, Global Assessment of Function,
      and remission rate. The time course of response and dropout rates was also
      compared. RESULTS: Sarcosine decreased immobility in the forced swim test and
      tail suspension test, reduced the latency to feed in the novelty-suppressed
      feeding test, and reversed behavioral deficits caused by chronic unpredictable
      stress test, which are characteristics for an antidepressant. In the clinical
      study, sarcosine substantially improved scores of Hamilton Depression Rating
      Scale, Clinical Global Impression, and Global Assessment of Function more than
      citalopram treatment. Sarcosine-treated patients were much more likely and
      quicker to remit and less likely to drop out. Sarcosine was well tolerated
      without significant side effects. CONCLUSIONS: Our preliminary findings suggest
      that enhancing NMDA function can improve depression-like behaviors in rodent
      models and in human depression. Establishment of glycine transporter-I inhibition
      as a novel treatment for depression waits for confirmation by further proof-of
      principle studies.

PMID- 23562007
TI  - Fatal immune hemolytic anemia following allogeneic stem cell transplantation:
      report of 2 cases and review of literature.
AB  - Immune hemolytic anemia is a well-recognized complication after allogeneic
      hematopoietic stem cell transplantation (HSCT). There are 4 possible causes for
      this complication. First, antibodies present in the recipient destroy donor
      cells. Second, donor red cell antibodies at the time of stem cell infusion are
      transferred to the recipient. Third, sometimes, engrafted donor lymphocytes cause
      active production of red cell antibodies. Fourth, another cause of hemolysis
      after allogeneic HSCT is autoimmune hemolytic anemia (AIHA). It is thought to be
      due to antibodies produced by the donor's immune system against antigens on red
      cells of donor origin. Autoimmune hemolytic anemia after allogeneic HSCT is rare,
      it is still not well characterized, and it represents a life-threatening
      situation. We describe 2 patients with acute myeloid leukemia treated with
      intensive chemotherapy and umbilical cord blood stem cell transplantation (UCBT).
      One patient developed AIHA at day +182 and the other at day +212 after receiving
      UCBT. Patients received 5 and 7 line treatment options, respectively, including
      continuous corticosteroids, intravenous immunoglobulin, splenectomy,
      cyclophosphamide, plasma exchange, rituximab, bortezomib, and eculizumab.
      However, both patients died because of massive hemolysis after 85 and 106 days of
      intensive treatment, respectively. These cases reflect the extreme difficulty in
      the therapeutic management of patients with AIHA following UCBT. After an
      extensive review of the literature, the exact physiopathologic mechanisms of AIHA
      after allogeneic HSCT in general, and after UCBT in particular, and therefore an
      effective treatment remain unknown. 

PMID- 23562006
TI  - Cortisol levels and risk for psychosis: initial findings from the North American
      prodrome longitudinal study.
AB  - BACKGROUND: Studies of biomarkers of hypothalamic-pituitary-adrenal activity
      indicate that psychotic disorders are associated with elevated cortisol. This
      study examined cortisol levels in healthy control subjects and individuals who
      met clinical high-risk (CHR) criteria for psychosis. It was hypothesized that
      cortisol levels would be 1) elevated in the CHR group relative to control
      subjects, 2) positively correlated with symptom severity, and 3) most elevated in
      CHR patients who transition to psychotic level severity. METHODS: Baseline
      assessments were conducted at eight centers in the North American Prodrome
      Longitudinal Study. The present CHR sample included 256 individuals meeting the
      Scale for Prodromal Symptoms criteria and 141 control subjects, all of whom
      underwent baseline assessment and measurement of salivary cortisol. RESULTS:
      Consistent with previous reports, there was an effect of age on cortisol, with
      increases through the adolescent/early adult years. Analysis of covariance showed
      a main effect of diagnostic group, with the CHR group showing higher cortisol.
      There were modest, positive correlations of cortisol with baseline symptom
      severity, and analysis of covariance revealed higher baseline cortisol in those
      who transitioned to psychotic level symptoms when compared with healthy control
      subjects and CHR subjects who remitted. CONCLUSIONS: The present findings add to
      accumulating evidence of heightened cortisol secretion in CHR individuals. The
      findings also indicate nonspecific associations between cortisol levels and
      symptom severity, as well as symptom progression. The role of hypothalamic
      pituitary-adrenal activity in prediction of conversion to psychosis and its
      relation with other biomarkers of risk should receive attention in future
      research.

PMID- 23562008
TI  - Anti-interleukin-2 receptor alpha for multiple sclerosis?

PMID- 23562010
TI  - Self-reported menopausal symptoms in a racially diverse population and soy food
      consumption.
AB  - OBJECTIVES: Evaluate the association of self-reported vasomotor symptom (VMS)
      frequency with race/ethnicity among a diverse midlife US population and explore
      menopause symptom differences by dietary soy isoflavone (genistein+daidzein)
      consumption. STUDY DESIGN: Cross-sectional population-based study of peri- and
      postmenopausal women, ages 45-58. OUTCOMES: Recent VMS frequency, VMS ever;
      recent symptom bother (hot flashes, night sweats, headache and joint-ache).
      RESULTS: Of 18,500 potentially eligible women, 9325 returned questionnaires
      (50.4% response); 3691 were excluded (premenopausal, missing data, taking
      hormones). Of 5634 remaining women, 82.1% reported hot flashes ever, 73.1%
      reported night sweats ever; 48.8% and 38.6% reported recent hot flashes or night
      sweats, respectively. Compared with White women, Chinese, Japanese, Vietnamese,
      other Asian (each p<0.001) and Filipino (p<0.01) women less commonly reported
      ever having hot flashes; Asian women less commonly reported recent VMS bother
      (p<0.001). Black women more commonly reported hot flashes ever (p<0.05) and
      recent VMS bother (p<0.05). Compared with non-Hispanic White women, Hispanic
      women were less likely to report hot flashes (p<0.05) or night sweats (p<0.001)
      ever. Women were classified by isoflavone consumption: (1) none (n=1819), (2)
      0.01-4.30 mg/day (n=1931), (3) 4.31-24.99 mg/day (n=1347) and (4) >= 25 mg/day
      (n=537). There were no group differences in recent VMS number/day: (1) 7.0 (95%
      CI 6.5, 7.5); (2) 6.4 (95% CI 6.0, 7.1); (3) 7.0 (95% CI 6.3, 8.2); and (4) 6.8
      (95% CI 6.1, 7.7). CONCLUSIONS: Menopausal symptoms, independent of isoflavone
      intake, varied considerably by race/ethnicity and were least common among Asian
      races.

PMID- 23562011
TI  - Acoustic radiation force impulse imaging for reactive and malignant/metastatic
      cervical lymph nodes.
AB  - The aim of this study was to compare lymph node stiffness using acoustic
      radiation force impulse (ARFI) imaging in patients with cervical lymph node
      swelling. Forty-two cervical lymph nodes (reactive, n = 22; metastatic, n = 20)
      from 19 patients (13 men, 6 women; mean age, 63.68 +/- 14.9 y; range, 23-85 y)
      were examined between September 2011 and March 2012. The shear wave velocity
      (SWV, m/s) of each lymph node was evaluated by ARFI imaging. SWV of reactive
      lymph nodes was 1.52 +/- 0.48 m/s, and that of metastatic/malignant lymph nodes
      was 2.46 +/- 0.75 m/s. A SWV > 1.9 m/s was very useful metastatic lymph node
      classification, with 95.0% specificity, 81.8% sensitivity and 88.0% overall
      accuracy. The area under the receiver operating characteristic curve was 0.923
      (95% confidence interval, 0.842-1.000). ARFI imaging can be useful in the
      differentiation of reactive and malignant/metastatic cervical lymph nodes.

PMID- 23562012
TI  - Pre-clinical study of in vivo magnetic resonance-guided bubble-enhanced heating
      in pig liver.
AB  - Bubble-enhanced heating (BEH) can be exploited to increase heating efficiency in
      treatment of liver tumors with non-invasive high-intensity focused ultrasound
      (HIFU). The objectives of this study were: (i) to demonstrate the feasibility of
      increasing the heating efficiency of sonication exploiting BEH in pig liver in
      vivo using a clinical platform; (ii) to determine the acoustic threshold for such
      effects with real-time, motion-compensated magnetic resonance-guided thermometry;
      and (iii) to compare the heating patterns and thermal lesion characteristics
      resulting from continuous sonication and sonication including a burst pulse. The
      threshold acoustic power for generation of BEH in pig liver in vivo was
      determined using sonication of 0.5-s duration ("burst pulse") under real-time
      magnetic resonance thermometry. In a second step, experimental sonication
      composed of a burst pulse followed by continuous sonication (14.5 s) was compared
      with conventional sonication (15 s) of identical energy (1.8 kJ). Modification of
      the heating pattern at the targeted region located at a liver depth between 20
      and 25 mm required 600-800 acoustic watts. The experimental group exhibited near
      spherical heating with 40% mean enhancement of the maximal temperature rise as
      compared with the conventional sonication group, a mean shift of 7 +/- 3.3 mm
      toward the transducer and reduction of the post-focal temperature increase.
      Magnetic resonance thermometry can be exploited to control acoustic BEH in vivo
      in the liver. By use of experimental sonication, more efficient heating can be
      achieved while protecting tissues located beyond the focal point.

PMID- 23562009
TI  - Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT):
      a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Daclizumab, a humanised monoclonal antibody, modulates interleukin-2
      signalling by blocking the alpha subunit (CD25) of the interleukin-2 receptor. We
      assessed whether daclizumab high-yield process (HYP) would be effective when
      given as monotherapy for a 1 year treatment period in patients with relapsing
      remitting multiple sclerosis. METHODS: We did a randomised, double-blind, placebo
      controlled trial at 76 centres in the Czech Republic, Germany, Hungary, India,
      Poland, Russia, Ukraine, Turkey, and the UK between Feb 15, 2008, and May 14,
      2010. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were
      randomly assigned (1:1:1), via a central interactive voice response system, to
      subcutaneous injections of daclizumab HYP 150 mg or 300 mg, or placebo, every 4
      weeks for 52 weeks. Patients and study personnel were masked to treatment
      assignment, except for the site pharmacist who prepared the study drug for
      injection, but had no interaction with the patient. The primary endpoint was
      annualised relapse rate. Analysis was by intention to treat. The trial is
      registered with ClinicalTrials.gov, number NCT00390221. FINDINGS: 204 patients
      were assigned to receive placebo, 208 to daclizumab HYP 150 mg, and 209 to
      daclizumab HYP 300 mg, of whom 188 (92%), 192 (92%), and 197 (94%), respectively,
      completed follow-up to week 52. The annualised relapse rate was lower for
      patients given daclizumab HYP 150 mg (0.21, 95% CI 0.16-0.29; 54% reduction, 95%
      CI 33-68%; p<0.0001) or 300 mg (0.23, 0.17-0.31, 50% reduction, 28-65%;
      p=0.00015) than for those given placebo (0.46, 0.37-0.57). More patients were
      relapse free in the daclizumab HYP 150 mg (81%) and 300 mg (80%) groups than in
      the placebo group (64%; p<0.0001 in the 150 mg group and p=0.0003 in the 300 mg
      group). 12 (6%) patients in the placebo group, 15 (7%) of those in the daclizumab
      150 mg group, and 19 (9%) in the 300 mg group had serious adverse events
      excluding multiple sclerosis relapse. One patient given daclizumab HYP 150 mg who
      was recovering from a serious rash died because of local complication of a psoas
      abscess. INTERPRETATION: Subcutaneous daclizumab HYP administered every 4 weeks
      led to clinically important effects on multiple sclerosis disease activity during
      1 year of treatment. Our findings support the potential for daclizumab HYP to
      offer an additional treatment option for relapsing-remitting disease. FUNDING:
      Biogen Idec and AbbVie Biotherapeutics Inc.

PMID- 23562013
TI  - Accuracy of real-time single- and multi-beat 3-d speckle tracking
      echocardiography in vitro.
AB  - With little data published on the accuracy of cardiac 3-D strain measurements, we
      investigated the agreement between 3-D echocardiography and sonomicrometry in an
      in vitro model with a polyvinyl alcohol phantom. A cardiac scanner with a 3-D
      probe was used to acquire recordings at 15 different stroke volumes at a heart
      rate of 60 beats/min, and eight different stroke volumes at a heart rate of 120
      beats/min. Sonomicrometry was used as a reference, monitoring longitudinal,
      circumferential and radial lengths. Both single- and multi-beat acquisitions were
      recorded. Strain values were compared with sonomicrometer strain using linear
      correlation coefficients and Bland-Altman analysis. Multi-beat acquisition showed
      good agreement, whereas real-time images showed less agreement. The best
      correlation was obtained for a heart rate 60 of beats/min at a volume rate 36.6
      volumes/s.

PMID- 23562014
TI  - Evidence for trapped surface bubbles as the cause for the twinkling artifact in
      ultrasound imaging.
AB  - The mechanism of the twinkling artifact (TA) that occurs during Doppler
      ultrasound imaging of kidney stones was investigated. The TA expresses itself in
      Doppler images as time-varying color. To define the TA quantitatively, beam
      forming and Doppler processing were performed on raw per channel radio-frequency
      data collected when imaging human kidney stones in vitro. Suppression of
      twinkling by an ensemble of computer-generated replicas of a single radio
      frequency signal demonstrated that the TA arises from variability among the
      acoustic signals and not from electronic signal capture or processing. This
      variability was found to be random, and its suppression by elevated static
      pressure and return when the pressure was released suggest that the presence of
      bubbles on the stone surface is the mechanism that gives rise to the TA.

PMID- 23562015
TI  - Mechanotransduction of ultrasound is frequency dependent below the cavitation
      threshold.
AB  - This study provides evidence that low-intensity ultrasound directly affects
      nuclear processes, and the magnitude of the effect varies with frequency. In
      particular, we show that the transcriptional induction of first load-inducible
      genes, which is independent of new protein synthesis, is frequency dependent.
      Bovine chondrocytes were exposed to low-intensity (below the cavitational
      threshold) ultrasound at 2, 5 and 8 MHz. Ultrasound elevated the expression of
      early response genes c-Fos, c-Jun and c-Myc, maximized at 5 MHz. The
      phosphorylated ERK inhibitor PD98059 abrogated any increase in c-series gene
      expression, suggesting that signaling occurs via the MAPPK/ERK pathway. However,
      phosphorylated ERK levels did not change with ultrasound frequency, indicating
      that processes downstream of ERK phosphorylation (such as nuclear transport and
      chromatin reorganization) respond to ultrasound with frequency dependence. A
      quantitative, biphasic mathematical model based on Biot theory predicted that
      cytoplasmic and nuclear stress is maximized at 5.2 +/- 0.8 MHz for a chondrocyte,
      confirming experimental measurements.

PMID- 23562017
TI  - Microbubble-enhanced ultrasound liberation of mRNA biomarkers in vitro.
AB  - Blood-borne biomarkers have great potential in diagnostic medicine, but low
      concentrations, inability to determine their source and lack of a patient
      baseline have limited their success in both research and clinical medicine.
      D'Souza et al. previously demonstrated that ultrasound-induced sonoporation can
      be used to liberate protein biomarkers from a colorectal cancer into the
      surrounding serum, overcoming many of the limitations of blood-borne biomarkers.
      In this study we build on D'Souza's work, extending this technique to nucleic
      acids, specifically mammaglobin mRNA-a potential diagnostic biomarker for breast
      cancer metastases. Furthermore, we propose to use ultrasound contrast agents,
      lipid-stabilized microbubbles, to enhance the effects of sonoporation and further
      amplify the biomarker levels. We demonstrate that microbubbles can enhance
      mammaglobin mRNA levels by two to three orders of magnitude greater than
      background levels and one to two orders of magnitude greater than ultrasound
      alone.

PMID- 23562016
TI  - The value of high-frequency ultrasonographic imaging for quantifying trigger
      digits: a correlative study with clinical findings in patients with different
      severity grading.
AB  - Trigger digit is recognized as thickening and constriction of the flexor tendon
      sheath at the base of digits. This study investigates the correlation between the
      severity grading of trigger digits and clinical findings from high-frequency
      ultrasonography. We measured and compared thicknesses, areas and pathological
      changes of the flexor digit tendons among total, contracture and noncontracture
      trigger digits and noninvolved contralateral digits. Forty-seven patients with 55
      idiopathic trigger digits (36 contracture and 19 noncontracture) and 55
      noninvolved contralateral digits were examined using high-frequency
      ultrasonography. The thickness of the flexor tendons was measured in a
      longitudinal plane at the A1 pulley: Inlet (metacarpal head-neck junction),
      Outlet (proximal phalangeal base-shaft junction) and Interpulley (middle of Inlet
      and Outlet). The cross-sectional and extratendinous tissue areas of the flexor
      tendons in a transverse plane at the point of Interpulley were measured.
      Pathological changes including irregular internal echotextures, fluid collection,
      dominant A1 pulley and abnormal metacarpophalangeal joint were analyzed. All
      thicknesses and areas of total and contracture trigger digits were significantly
      greater than those of noninvolved contralateral digits (p < 0.05), whereas no
      significant difference was observed in noncontracture trigger digits. The
      pathological changes were all significantly different from noninvolved
      contralateral digits in total, contracture and noncontracture trigger digits (p <
      0.05). In contracture and noncontracture trigger digits, there were significant
      differences only in the thickness of the Inlet and the pathological change of the
      dominant A1 pulley (p < 0.05). In conclusion, the results of the ultrasonographic
      measurements and findings provided evidence of Notta's node and correlated with
      clinical findings and severity grades.

PMID- 23562018
TI  - Classification of breast tumors using elastographic and B-mode features:
      comparison of automatic selection of representative slice and physician-selected
      slice of images.
AB  - Inter-observer variability and image quality are two key factors that can affect
      the diagnostic performance of elastography and B-mode ultrasound for breast tumor
      characterization. The purpose of this study is to use an image quantification
      method that automatically chooses a representative slice and then segments the
      tumor contour to evaluate the diagnostic features for tumor characterization.
      First, the representative slice is selected based on either the stiffness inside
      the tumor (the signal-to-noise ratio on the elastogram [SNRe]) or the contrast
      between the tumor and the surrounding normal tissue (the contrast-to-noise ratio
      on the elastogram [CNRe]). Next, the level set method is used to segment the
      tumor contour. Finally, the B-mode and elastographic features related to the
      segmented tumor are extracted for tumor characterization. The performance of the
      representative slice selected using the proposed methods is compared to that of
      the physician-selected slice in 151 biopsy-proven lesions (89 benign and 62
      malignant). The diagnostic accuracies using elastographic features are 82.1%
      (124/151) for the slice with the maximum CNRe value, 82.1% (124/151) for the
      slice with the maximum SNRe value and 82.8% (125/151) for the physician-selected
      slice, whereas the diagnostic accuracies using B-mode features are 80.8%
      (122/151) for the slice with the maximum CNRe value, 87.4% (132/151) for the
      slice with the maximum SNRe value and 84.1% (127/151) for the physician-selected
      slice. When using both the B-mode and elastographic features to characterize the
      tumor, the accuracy of diagnosis is 86.1% (130/151) for the slice with the
      maximum CNRe value, 90.1% (136/151) for the slice with the maximum SNRe value and
      89.4% (135/151) for the physician-selected slice. Our results show that the
      representative slice selected by SNRe and CNRe could be used to reduce the
      observer variability and to increase the diagnostic performance by the B-mode and
      elastographic features.

PMID- 23562019
TI  - Characterization of the ultrasound beam produced by the MIST therapy, wound
      healing system.
AB  - The MIST Therapy wound healing device (Celleration, Eden Prairie, MN, USA), which
      uses low-frequency ultrasound to deliver an atomized saline spray to acute
      wounds, was evaluated in a laboratory environment. The output of the MIST device
      was characterized by its frequency, transmission in the presence and absence of
      the saline spray and intensity. When measured up to 500 mm away from the
      transducer tip, the transmission of 39.5 kHz ultrasound was not significantly
      attenuated by the saline itself. In the absence of the saline spray, the acoustic
      intensity range of the MIST device was calculated to be 429-188 mW cm(-2) across
      the manufacturer-specified treatment range (12.5-20 mm). Because of the acoustic
      impedance mismatch between air and soft tissue, the MIST Therapy device would
      deliver only 0.1% of this incident intensity into the wound site.

PMID- 23562020
TI  - Ultrasonic manipulation of yeast cells in suspension for absorption spectroscopy
      with an immersible mid-infrared fiberoptic probe.
AB  - Recent advances in combining ultrasonic particle manipulation with attenuated
      total reflection infrared spectroscopy of yeast suspensions are presented.
      Infrared spectroscopy provides highly specific molecular information about the
      sample. It has not been applicable to in-line monitoring of cells during
      fermentation, however, because positioning cells in the micron-thin measurement
      region of the attenuated total reflection probe was not possible. Ultrasonic
      radiation forces exerted on suspended particles by an ultrasonic standing wave
      can result in the buildup of agglomerates in the nodal planes, hence enabling the
      manipulation of suspended cells on the microscopic scale. When a chamber setup
      and a prototype in-line applicable probe were used, successful control over the
      position of the yeast cells relative to the attenuated total reflection sensor
      surface could be proven. Both rate of increase and maximum mid-infrared
      absorption of yeast-specific bands during application of a pushing frequency
      (chamber setup: 1.863 MHz, in-line probe: 1.990 MHz) were found to correlate with
      yeast cell concentration.

PMID- 23562021
TI  - Ultrasound-based diagnosis for solid thyroid nodules with the largest diameter <5
      mm.
AB  - This study was aimed at assessing the efficacy of using an ultrasound (US)-based
      classification system to diagnose solid thyroid nodules with the largest diameter
      <5 mm (i.e., small solid nodules). For 406 small solid nodules in 365 patients
      who underwent thyroid US and US-guided fine-needle aspiration, each thyroid
      nodule was prospectively classified into one of five diagnostic categories:
      benign, probably benign, borderline, possibly malignant and malignant. Of 406
      nodules, 145 were surgically removed: 95 papillary thyroid carcinomas, 1
      follicular thyroid carcinoma, 1 poorly differentiated carcinoma, 3 pseudonodules
      related to thyroiditis and 45 nodular hyperplasias. On the basis of the
      histopathologic results, the diagnostic accuracies of US diagnosis and cytologic
      diagnosis were similar, but the sensitivity of US diagnosis was higher than that
      of cytologic diagnosis, and the specificity and positive predictive values of US
      diagnosis were lower those of cytologic diagnosis. An US-based classification
      system may be helpful for the diagnosis and management of small solid nodules.

PMID- 23562022
TI  - Liver fibrosis assessment using transient elastography guided with real-time B
      mode ultrasound imaging: a feasibility study.
AB  - Liver fibrosis is a kind of chronic damage of the liver and can lead to
      cirrhosis, one of the top 10 causes of death in the Western world. However, there
      is still a lack of noninvasive methods for diagnosing liver fibrosis. Fibroscan
      (Echosens, Paris, France), a device based on A-mode transient elastography, has
      shown promising results. In this study, a transient elastography system with real
      time B-mode imaging for non-invasive liver fibrosis assessment, named Liverscan,
      was developed; its performance was tested and compared with that of the
      Fibroscan. A specific measurement probe was designed and fabricated with a B-mode
      ultrasound transducer fixed along the axis of a mechanical vibrator. It was
      integrated with the Liverscan to measure liver stiffness based on the shear wave
      propagation in liver tissues. The system was validated by mechanical indentation
      test using custom-made agar-gelatin phantoms with different stiffness. To further
      test its feasibility, in vivo measurements were conducted in 67 volunteers (age,
      34 +/- 3 years; body mass index, 21.3 +/- 2.8 kg/m(2); Mean +/- SD., 34 male and
      33 female), including 20 patients with various liver diseases, and 28 (19 male
      and 9 female) being tested by both Liverscan and Fibroscan. A significant linear
      correlation between the stiffness measured by the mechanical indentation test and
      that by the Liverscan (r = 0.973; p < 0.001) was obtained. The in vivo liver
      stiffness measured by Liverscan was also correlated with that by Fibroscan
      significantly (r = 0.886; p < 0.001). There was a significant difference in liver
      stiffness between the 20 patients and the other healthy subjects (14.1 +/- 3.4
      kPa vs. 10.5 +/- 2.1 kPa; p = 0.001). The intra- and inter-observer tests
      indicated that the measurements were repeatable with intra-class correlation
      coefficients being 0.987 (p < 0.001) and 0.988 (p < 0.001), respectively. This
      study demonstrated that Liverscan with a specifically designed probe was able to
      measure and differentiate liver of different stiffness using the established
      measurement protocol under the guidance of real-time B-mode ultrasound imaging.

PMID- 23562023
TI  - In vitro gene delivery with ultrasound-triggered polymer microbubbles.
AB  - In the work described here, gene delivery using polymer microbubbles triggered by
      ultrasound in vitro was investigated. The effects of pressure amplitude (0-2
      MPa), center frequency (1-5 MHz), pulse length (3-12,000 MUs), pulse repetition
      frequency (5-20,000 Hz) and exposure time (0-30 s) on transfection efficiency and
      cell viability were examined. The effects of radiation force, calcium ion
      concentration and timing of treatments were also examined. Cells were
      successfully transfected with pressure amplitudes as low as 250 kPa. Transfection
      was most efficient at lower frequencies and longer pulse lengths, with a
      transfection efficiency of 24.2 +/- 2.0% achieved using a center frequency of 1
      MHz, pressure amplitude of 1 MPa, pulse length of 12,000 MUs and pulse repetition
      frequency of 5 Hz. Gene delivery was also affected by the extracellular calcium
      ion concentration and the timing of treatments.

PMID- 23562024
TI  - Introduction of a new index of cervical consistency with transvaginal B-mode
      ultrasonography.
AB  - Changes in the length and consistency of the uterine cervix during pregnancy are
      known to precede pre-term labor. However, cervical consistency has not been
      studied in depth because its objective evaluation requires special equipment. Our
      aim was to define a new index to evaluate cervical consistency simply and easily
      using B-mode ultrasonography. The cervical length-consistency index (CLCI) is
      defined as the ratio of the length of the cervix stretched during compression to
      that before compression. CLCI increases as pregnancy progresses. The CLCI values
      that corresponded to digital examination results of firm, medium and soft were
      112.0 +/- 10.0, 124.1 +/- 22.4 and 153.2 +/- 35.7, respectively, thus confirming
      the existence of a significant relationship between the index and consistency.
      The CLCI may be useful in predicting pre-term labor and should therefore be
      investigated further in larger cohorts.

PMID- 23562025
TI  - Response to Dr Kesel's letter to the editor:.

PMID- 23562026
TI  - Castration eliminates conspecific aggression in group-housed CD1 male
      surveillance mice (Mus musculus).

PMID- 23562028
TI  - Nonsurgical embryo transfer device compared with surgery for embryo transfer in
      mice.
AB  - The use of a murine nonsurgical embryo transfer (NSET) device had been described
      previously for the transfer of blastocysts, morulae, DNA-microinjected embryos,
      and embryonic stem cell-containing embryos to create genetically modified mice.
      However, physiologic effects of the NSET device and traditional surgical methods
      had not been compared directly. Here we used electrocardiography and fecal
      corticosterone levels to monitor pseudopregnant mice that underwent anesthesia
      only, the NSET procedure with or without anesthesia, or surgery. These procedures
      were performed without the use of actual embryos, to focus on effects of the
      procedures themselves rather than on any physiologic effects due to the
      deposition of embryos. As compared with surgery and anesthesia, the NSET
      procedure was associated with less fluctuation in cardiac rhythm and lower levels
      of the stress biomarker fecal corticosterone. These results indicate that use of
      the NSET device avoids these physi- ological perturbations as well as other
      disadvantages of surgery (for example, postoperative pain and need for
      postoperative analgesia) and therefore provides a valuable refinement of existing
      mouse embryo transfer procedures.

PMID- 23562027
TI  - Analgesic use in nonhuman primates undergoing neurosurgical procedures.
AB  - Animals experiencing major invasive surgery during biomedical research must
      receive appropriate and sufficient analgesia. The concept of pain management in
      veterinary medicine has evolved over the past several decades, and a multimodal,
      preemptive approach to postoperative analgesia is the current standard of care.
      Here, the pathophysiology of pain and a multimodal approach to analgesia for
      neurosurgical procedures is discussed, with emphasis on those involving nonhuman
      primates.

PMID- 23562029
TI  - Leaching of heavy metals from water bottle components into the drinking water of
      rodents.
AB  - Providing high-quality, uncontaminated drinking water is an essential component
      of rodent husbandry. Acidification of drinking water is a common technique to
      control microbial growth but is not a benign treatment. In addition to its
      potential biologic effects, acidified water might interact with the water
      delivery system, leading to the leaching of heavy metals into the drinking water.
      The goal of the current study was to evaluate the effects of water acidification
      and autoclaving on water-bottle assemblies. The individual components of the
      system (stainless-steel sipper tubes, rubber stoppers, neoprene stoppers, and
      polysulfone water bottles) were acid-digested and analyzed for cadmium, chromium,
      copper, iron, lead, magnesium, manganese, selenium, and zinc to quantify the
      metal composition of each material. In addition the amounts of these metals that
      leached into tap and acidified water with and without autoclaving were quantified
      after 1 wk of contact time. On a weight basis, sipper tubes contained the largest
      quantities of all metals except magnesium and zinc, which were greatest in the
      neoprene stoppers. Except for cadmium and selenium, all metals had leached into
      the water after 1 wk, especially under the acidified condition. The quantities of
      copper, lead, and zinc that leached into the drinking water were the most
      noteworthy, because the resulting concentrations had the potential to confound
      animal experiments. On the basis of these findings, we suggest that water-quality
      monitoring programs include heavy metal analysis at the level of water delivery
      to animals.

PMID- 23562030
TI  - PCR testing of a ventilated caging system to detect murine fur mites.
AB  - Rodents housed in microisolation caging are commonly monitored for infectious
      agents by the use of soiled bedding sentinels. This strategy relies on the
      successful transmission of rodent pathogens from the index rodents via soiled
      bedding to sentinel cages and the subsequent infection or colonization of
      sentinel rodents. When the prevalence of a pathogen is low or the target agent is
      not readily transmitted by soiled bedding, alternative testing methodologies
      should be used. Given the continued prevalence of institutions self-reporting
      murine fur mites and with the advent of a new sensitive and specific PCR assay
      for mites, we sought to determine whether the exhaust system of an individual
      ventilated caging (IVC) system could be used for monitoring the rack's rodent
      population for mites rather than relying on the responses of sentinels. We
      deployed single cages of mice (Mus musculus) that were known to be infested with
      either Radfordia affinis or Myobia musculi on a 70-cage rack, sampled the
      horizontal exhaust manifolds weekly, and used the new PCR assay to test these
      samples for mite DNA. We detected the presence of fur mites at a 94.1%
      probability of detection within 4 wk of placement. Therefore, we recommend
      swabbing and testing the shelf exhaust manifolds of IVC racks rather than relying
      on soiled-bedding sentinels as an indicator of the mite status of the rodents on
      that rack.

PMID- 23562031
TI  - Effects of injectable anesthetic combinations on left ventricular function and
      cardiac morphology in Sprague-Dawley rats.
AB  - Novel anesthetic agents or combinations may provide superior general anesthesia
      for echocardiography in rodents with the potential for reduced adverse effects.
      This study sought to characterize the effects of 3 injectable anesthetics on left
      ventricular (LV) systolic function and cardiac morphology in healthy male and
      female rats. Rats underwent echocardiographic assessment after general anesthesia
      via pentobarbital or combinations of ketamine and medetomidine (KME) and ketamine
      and midazolam (KMI) according to a crossover Latin-square design. Blood samples
      for serum estradiol measurements were obtained from all females after
      echocardiography with each anesthetic. Rats given KMI showed superior LV systolic
      function with the highest values for fractional shortening (FS), ejection
      fraction (EF) and stroke volume, whereas heart rate was greatest with
      pentobarbital, followed by KMI and then KME. KME produced the greatest effects on
      cardiac morphology, most notably during systole, including reduced septal and
      posterior wall thickness and increased LV chamber dimensions and volumes. In
      addition, KME had the greatest cardiac-depressing effects on LV systolic
      function, including reduced FS, EF, and heart rate values. Compared with male
      rats, female rats had superior LV function with greater EF and FS values, whereas
      male rats showed higher heart rate. Significant negative correlations were noted
      between serum estradiol levels and FS and EF values in female rats receiving KME.
      We conclude that the combination of KMI may be a superior anesthetic for use in
      male and female rats undergoing echocardiography.

PMID- 23562032
TI  - Thermal threshold testing for evaluation of analgesics in New Zealand white
      rabbits.
AB  - We adapted a thermal analgesiometric device developed for cats for use in
      unrestrained rabbits. A probe composed of an electrical element and temperature
      sensor was held against shaved skin by using an elasticized band placed
      circumferentially around the thorax. An inflated bladder located between the
      probe and elastic maintained constant contact between probe and skin. The probe
      was heated until the rabbit displayed a behavioral reaction or the safety cutoff
      of 55  degrees C was reached. Threshold temperatures in unmedicated rabbits were
      stable over a 5-h period provided that tests were 15 min or more apart. Careful
      acclimation and testing resulted in no false-negative responses, and sham testing
      did not produce false-positive results. When compared with baseline values,
      thermal thresholds were significantly increased from 30 to 240 min, but not 300
      min, after the administration of morphine at 3 mg/kg. Administration of
      equivalent volumes of saline via the same route had no effect on thermal
      threshold. This device may be suitable for investigating analgesic pharmacology
      in rabbits.

PMID- 23562033
TI  - Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta
      and Macaca fascicularis).
AB  - Buprenorphine is the cornerstone of pain management in nonhuman primates, but the
      pharmacokinetics of this widely used drug are unknown. The purpose of this study
      was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03
      mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species
      (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics
      did not differ significantly between species, and buprenorphine was dose
      proportional at the tested doses. The low and high doses of buprenorphine had
      elimination half-lives of 2.6 +/- 0.7 and 5.3 +/- 2.0 h, respectively, but the
      low-dose data were constrained by the sensitivity of the analytical method.
      Sustained-release buprenorphine had an elimination half-life of 42.6 +/- 26.2 h.
      The AUC0-Tlast of buprenorphine were 9.1 +/- 4.3 and 39.0 +/- 25.1 ng * h/mL for
      the low and high doses, respectively, and sustained-release buprenorphine had an
      AUC0-Tlast of 177 +/- 74 ng * h/mL. Assuming a hypothesized therapeutic
      buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these
      results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered
      every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h.
      These results further demonstrate that a single 0.2-mg/kg SC injection of
      sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL
      for 5 d in macaques. These findings support a new dosing strategy using sustained
      release buprenorphine to improve pain management, decrease animal stress, improve
      animal welfare, and simplify the postoperative management of nonhuman primates in
      laboratory animal and zoological settings.

PMID- 23562034
TI  - Effects of acute administration of ketorolac on mammalian vestibular sensory
      evoked potentials.
AB  - The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use
      as a supplemental analgesic during major surgery in anesthetized rodents. The use
      of ketorolac during surgery is believed to reduce the anesthetic dose required to
      achieve and maintain an adequate surgical plane, thus improving the physiologic
      condition and survival of animals during long experimental procedures. Ketorolac
      has reported side effects that include dizziness, ear pain, hearing loss,
      tinnitus, and vertigo in humans, but ketorolac has not been reported to affect
      the vestibular system in animals. To investigate this possibility, we evaluated
      the acute effects of ketorolac on vestibular compound action potentials in
      C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded
      during the administration of ketorolac at doses 3 to 14 times the effective
      analgesic dose. VsEP results for ketorolac were compared with those from a
      control group maintained under anesthesia for the same period. Ketorolac did not
      significantly affect the temporal profiles of response latencies and amplitudes
      or the rate of change in response measures over time between controls and
      ketorolac-treated mice. These findings demonstrate that ketorolac can be used as
      an analgesic to supplement anesthesia in mice without concerns of modifying the
      amplitudes and latencies of the linear VsEP.

PMID- 23562035
TI  - Clean technique for prolonged nonsurvival cardiothoracic surgery in swine (Sus
      scrofa).
AB  - Laboratory animal regulations provide little guidance regarding duration of
      nonsurvival surgery requiring aseptic technique. We hypothesized that swine would
      experience no sepsis during nonsurvival cardiothoracic surgery accomplished by
      using clean technique and lasting 8 h or less. Incision sites of 5 male farm pigs
      (Sus scrofa) were shaved and then cleaned with alcohol and povidone-iodine. The
      surgeon wore sterile gloves, clean scrubs, and hair bonnet; assistants wore clean
      scrubs and nonsterile gloves; most instruments were autoclaved. A median
      sternotomy incision was used for thoracic cavity exposure, and the skull was
      exposed to allow induction of brain death. Heart rate, body temperature, and
      blood samples were obtained before surgery (0 h; baseline) and at 2, 4, 5 or 6,
      and 7 or 8 h thereafter. Statistical analysis by t-tests showed that heart rate
      was unchanged and body temperature increased after the 0-h (baseline) time point.
      Aerobic blood cultures were negative except for 2 samples that were positive for
      coagulase-negative Staphylococcus spp. at 4 h. RBC, Hgb, and Hct levels were
      decreased at 2 and 4 h, but WBC and platelets were unchanged. Other alterations
      included decreased glucose (at 7 or 8 h), increased BUN (at 5 or 6 h and 7 or 8
      h) and creatinine (at 5 or 6 h), decreased Na(+) and Ca and increased K(+) (most
      time points), decreased total protein and albumin (most time points), and
      decreased globulin (at 7 or 8 h). Liver enzymes and bilirubin typically were
      unchanged, and cholesterol consistently was decreased. Together our results
      indicate a lack of sepsis for 8 h or less in pigs undergoing cardiothoracic
      surgery by using clean technique. These findings provide new and specific data
      regarding the use of aseptic technique during prolonged nonsurvival surgeries.

PMID- 23562036
TI  - Leukapheresis protocol for nonhuman primates weighing less than 10 kg.
AB  - Leukapheresis is a common procedure for hematopoietic cell transplantation in
      adults. The main challenge in applying this procedure to human infants and small
      monkeys is the large extracorporeal blood volume (165 mL on average) necessary
      for priming the apheresis machine. This volume represents greater than 50% of the
      total circulating blood volume of a human neonate or small monkey. In this
      report, we document a safe leukapheresis protocol developed for rhesus macaques
      (3.9 to 8.7 kg). To avoid sensitizing donor animals undergoing leukapheresis to
      third-party blood products, autologous blood collected during the weeks prior to
      leukapheresis was used to volume-expand the same donor while priming the machine
      with saline on the day of leukapheresis. During the procedures, blood pressure
      was controlled by monitoring the inlet volume, and critical-care support was
      provided by the anesthesia team. Electrolytes and hemogram parameters were
      monitored intermittently. Overall, our research subjects underwent effective 4-
      to 6-h leukapheresis. A total of 9 leukapheresis procedures were performed, which
      yielded 1 * 10(9) to 6 * 10(9) peripheral blood mononuclear cells containing 1.1
      to 5.1 * 10(6) CD34(+) cells (assessed in 4 of 9 macaques) in a volume of 30 to
      85 mL. All macaques showed decreases in Hct and platelet counts. In summary, we
      report a successful modified leukapheresis procedure that can be performed safely
      in small animals without modification of the leukapheresis machine or associated
      cell-collection kits.

PMID- 23562037
TI  - Correlation of thoracic radiograph measurements with age in adolescent Chinese
      rhesus macaques (Macaca mulatta).
AB  - Thoracic radiography has been applied extensively to cardiovascular or
      respiratory disorders in veterinary practice and in research using animal models.
      To establish baseline measures for various parameters of thoracic radiography, we
      used a cross-sectional method to collect the lung length (LL), maximum interior
      thoracic breadth (TBr), maximum breadth of the cardiac silhouette (CBr),
      cardiothoracic ratio (CR), and right hilar height ratio (RHHR) of random healthy
      captive Chinese rhesus monkeys (age, 1 to 5 y; 89 male, 64 female). Significant
      sex-associated differences occurred in TBr among 1-y-old subjects and RHHR in 2-
      and 3-y-old monkeys. In addition, LL, TBr, and CBr were significantly correlated
      with age in both sexes. Finally, stepwise multiple regression revealed that LL
      and CBr were predictors of age in female monkeys, whereas LL and TBr were age
      predictive in male macaques. The current data may suggest caveats regarding the
      use of thoracic radiography for evaluating disease processes, including pulmonary
      tuberculosis, hydropericardium, and heart failure, and for assessing physical
      development in adolescent rhesus macaques.

PMID- 23562038
TI  - Unsterilized feed as the apparent cause of a mouse parvovirus outbreak.
AB  - In early 2009, we experienced a widespread outbreak of mouse parvoviruses 1 and 2
      (MPV) at our institution, which encompasses approximately 50,000 cages located in
      7 campus vivaria. MPV had not been detected for several years; however, during a
      single 4-mo sentinel-testing rotation comprising all racks at the institution, 72
      of 927 rack sentinels tested serologically positive for MPV1, MPV2, or both. PCR
      of fecal samples from several index cases confirmed MPV. Each sentinel-positive
      rack contained between 0 and 10 infected colony cages. Positive racks appeared to
      be randomly distributed, although several small facilities escaped infection. We
      investigated how this infection may have entered the facilities, in which mice
      were maintained in barrier caging with sterilized feed, bedding, and equipment,
      and procedures were in place to prevent incoming infection and cross
      contamination. The only widespread change that occurred during the 3 mo preceding
      the first positive test was that every cage had been treated for 12 wk with an
      unsterilized fenbendazole-medicated diet. At the completion of fenbendazole
      treatment, sterilized feed was reinstituted. Evidence of MPV infection was
      eliminated within 7 mo via an intensive test-and-remove policy in combination
      with movement controls, and we have had no further positive tests in the 3.5 y
      since the outbreak. Although the possibility remains that MPV infection resulted
      from fomites or undetected infections in incoming mice, the timing and extent of
      this outbreak together with the complete absence of new cases after sterilized
      feed was reinstituted strongly implicate unsterilized feed as the source of this
      MPV outbreak.

PMID- 23562039
TI  - Primate Medicine Then and Now- 40 Years of the APV Workshop.

PMID- 23562040
TI  - Investigation of photosynthetic membrane structure using atomic force microscopy.
AB  - Photosynthetic processes, including light capture, electron transfer, and energy
      conversion, are not only ensured by the activities of individual photosynthetic
      complexes but also substantially determined and regulated by the composition and
      assembly of the overall photosynthetic apparatus at the supramolecular level. In
      recent years, atomic force microscopy (AFM) has matured as a unique and powerful
      tool for directly assessing the supramolecular assembly of integral membrane
      protein complexes in their native membrane environment at submolecular
      resolution. This review highlights the major contributions and advances of AFM
      studies to our understanding of the structure of the bacterial photosynthetic
      machinery and its regulatory arrangement during chromatic adaptation. AFM
      topographs of other biological membrane systems and potential future applications
      of AFM are also discussed.

PMID- 23562041
TI  - Risk of hepatitis B virus (HBV) reactivation in non-Hodgkin lymphoma patients
      receiving rituximab-chemotherapy: a meta-analysis.
AB  - BACKGROUND: The addition of Rituximab to standard chemotherapy (C) has been
      reported to improve the end of treatment outcome in non-Hodgkin lymphoma (NHL)
      patients. Nevertheless, rituximab has been associated with hepatitis B virus
      reactivation (HBV-R). OBJECTIVES: The aim of this systematic review and meta
      analysis is to research the relationship between rituximab and HBV-R. STUDY
      DESIGN: We searched the commonly used databases both in English and Chinese from
      November 1997 to June 30, 2012. Meta-analysis was performed in fixed/random
      effects models using Review Manager 5.1 and STATA 10.0. Publication bias was
      examined through Egger's test and Begg's funnel plot. RESULTS: Nine eligible
      articles were selected in this review (8 studies in English and 1 studies in
      Chinese), which included 971 adult patients and met all inclusion and exclusion
      criteria. Of rituximab-associated HBV-R cases reported through case series
      (n=387), 304 were HBcAb (+)/HBsAg (-) and 83 HBsAg (+). The pooled effect of
      rituximab-based therapy on HBV-R significantly increased under fixed-effects
      model [Relative risk (RR) 2.14, 95%CI 1.42-3.22, P=0.0003]. In subgroup analysis,
      rituximab-associated HBV-R in isolated HBcAb (+) patients remained high, and the
      RR was 5.52 (95%CI 2.05-14.85, P=0.0007). The RR of HBV-R in NHL patients with
      HBsAg (+) treated with R-based therapy when compared with the control population
      was 1.63 by the random-effects model. CONCLUSIONS: Rituximab therapy may increase
      the risk of developing HBV-R in NHL patients with HBcAb(+).

PMID- 23562042
TI  - Transfer of data or re-creation of knowledge - experiences of a shared electronic
      patient medical records system.
AB  - BACKGROUND: A shared electronic medical record (EMR) can improve communication
      between primary and secondary care. A consideration of the contents using Data
      Information-Knowledge-Wisdom (DIKW) hierarchy could help inform further
      development of such systems regarding communication about prescribed medication.
      OBJECTIVES: To investigate primary and secondary care doctors' experiences of the
      shared EMR in Uppsala, Sweden, focusing on the creation, use and cross-sector
      transfer of data, information, knowledge and wisdom about individual patients'
      prescribed medication. METHOD: Nine focus groups were held with hospital doctors,
      of different grades and medical specialties, working at a single large teaching
      hospital in Uppsala, Sweden and primary care doctors worked in the same
      geographical area, in urban and rural primary care centers. The transcribed data
      were analyzed used the constant comparative method, based on data from the
      participants and application of the DIKW hierarchy. RESULTS: The doctors were
      very positive about accessing and using the shared EMR. Data and information in
      the system were efficiently retrieved and combined with newly collected data and
      information to create further knowledge. However, they also described a data and
      information overload, where it was difficult to get a general overview of what
      had happened over time, coupled with the frequent lack of knowledge being created
      and shared by other healthcare providers. Doctors were, instead, either
      explicitly asked or implicitly expected to read and interpret all available data
      and information and recreate knowledge themselves. CONCLUSIONS: This study
      highlighted the differences between access to data and information and access to
      knowledge in a shared EMR. In rolling out such a system, an increased
      availability of data and information should not be at the expense of a reduced
      availability of knowledge.

PMID- 23562043
TI  - Epidemiology of pediatric primary malignant central nervous system tumors in
      Iran: a 10 year report of National Cancer Registry.
AB  - BACKGROUND: CNS tumors are the leading cause of cancer related deaths among
      children and adolescents. Nonetheless, the incidence of pediatric CNS tumors in
      developing countries is poorly understood. We aimed to provide epidemiologic
      features of primary malignant CNS tumors in Iranian children 0-19 years of age
      using National Cancer Registry (NCR) data bank. METHODS: The data recorded by NCR
      over a 10 year period (2000-2010) were reviewed. RESULTS: Of 1948 tumor cases,
      93.3% were located in brain, 5.1% were found in the spinal cord & cauda equina,
      and 1.6% affected cranial nerves and other parts of the nervous system. The
      overall average annual age specific incidence rate was 1.43 per 100,000. Males
      were more likely to develop CNS tumors (1.65 per 100,000) compared to females
      (1.21 per 100,000, p<0.01). Children under 5 years of age had the highest age
      specific incidence rate (1.86 per 100,000). Astrocytic tumors with the incidence
      rate of 0.61 per 100,000 were the most frequent specific histology followed by
      embryonal (0.38 per 100,000), and ependymal tumors (0.10 per 100,000). With
      regard to the histological distribution of tumors, some unique features including
      the high proportion of unspecified malignant neoplasms (7.6%) were noted.
      CONCLUSION: The overall incidence rate was markedly lower than western findings.
      Major differences were also observed in incidence rates of specific histologies.
      Although the discrepancies may be attributable to diversity in classification
      schemes and registration practices, a real ethnic and geographical variation in
      predisposition to development of pediatric CNS cancers is strongly suggested.

PMID- 23562044
TI  - Birth weight and other perinatal factors and childhood CNS tumors: a case-control
      study in California.
AB  - AIMS: We conducted a large registry-based study in California to investigate the
      association of perinatal factors and childhood CNS tumors, with analysis by tumor
      subtype. METHODS: We linked California cancer and birth registries to obtain
      information on 3308 cases and 3308 controls matched on age and sex. We examined
      the association of birth weight, gestational age, birth order, parental ages,
      maternal conditions during pregnancy, newborn abnormalities and the risk of
      childhood CNS tumors using conditional logistic regression, with adjustment for
      potential confounders. RESULTS: The odds ratio (OR) per 1000 g increase in birth
      weight was 1.11 (95% CI: 0.99-1.24) for total childhood CNS tumors, 1.17 (95% CI:
      0.97-1.42) for astrocytoma and 1.28 (95% CI: 0.90-1.83) for medulloblastoma.
      Compared to average-for-gestational age, large-for-gestational age infants were
      at increased risk of glioma (OR=1.86, 95% CI: 0.99-3.48), while small-for
      gestational age infants were at increased risk of ependimoma (OR=2.64, 95% CI:
      1.10-6.30). Increased risk of childhood CNS tumors was observed for 5-year
      increase in maternal and paternal ages (OR=1.06, 95% CI: 1.00-1.12 and 1.05, 95%
      CI: 1.00-1.10 respectively). Increased risk of astrocytoma was detected for 5
      year increase in paternal age (OR=1.08; 95% CI: 1.00-1.16) and increased risk of
      glioma for maternal age >= 35 years old (OR=1.87; 95% CI: 1.00-3.52). Maternal
      genital herpes during pregnancy was associated with a pronounced increase in risk
      of total CNS tumors (OR=2.74; 95% CI: 1.16-6.51). Other (non-sexually
      transmitted) infections during pregnancy were associated with decreased risk of
      total CNS tumors (OR=0.28, 95% CI: 0.09-0.85). Maternal blood/immune disorders
      during pregnancy were linked to increased risk of CNS tumors (OR=2.28, 95% CI:
      1.08-4.83) and medulloblastoma (OR=7.13, 95% CI: 0.82-61.03). Newborn CNS
      abnormalities were also associated with high risk of childhood CNS tumors
      (OR=4.08, 95% CI: 1.13-14.76). CONCLUSIONS: Our results suggest that maternal
      genital herpes, blood and immunological disorders during pregnancy and newborn
      CNS abnormalities were associated with increased risk of CNS tumors. Maternal
      infections during pregnancy were associated with decreased risk of CNS tumors.
      Advanced maternal and paternal ages may be associated with a slightly increased
      risk of CNS tumors. Factors associated with CNS tumor subtypes varied by subtype,
      an indicator of different etiology for different subtypes.

PMID- 23562045
TI  - Fertility treatment and childhood cancer risk: a systematic meta-analysis.
AB  - OBJECTIVE: To clarify the association between fertility treatment and the risk
      for cancer in children. DESIGN: Meta-analysis. SETTING: None. PATIENT(S): Twenty
      five cohort and case-control studies involving children born after fertility
      treatment as the exposure of interest and cancer as the outcome. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Medline was searched through September 2012 to
      identify relevant studies. The study-specific estimates for each cancer outcome
      were combined into a pooled relative risk (RR) with 95% confidence interval (CI)
      by a meta-analytic approach. RESULT(S): We found that children born after
      fertility treatment were at increased risk for all cancers (RR = 1.33; 95% CI,
      1.08-1.63) and for hematological cancers (RR = 1.59; 95% CI, 1.32-1.91), central
      nervous system/neural cancers (RR = 1.88; 95% CI, 1.02-3.46), and other solid
      cancers (RR = 2.19; 95% CI, 1.26-3.80). For specific cancer types, we found
      increased risks for leukemias (RR = 1.65; 95% CI, 1.35-2.01), neuroblastomas (RR
      = 4.04; 95% CI, 1.24-13.18), and retinoblastomas (RR = 1.62; 95% CI, 1.12-2.35)
      associated with fertility treatment. CONCLUSION(S): The results of the largest
      meta-analysis on this topic to date indicate an association between fertility
      treatment and cancer in offspring. However, our results do not rule out that
      factors related to underlying subfertility, rather than the procedure itself, are
      the most important predisposing factors for childhood cancer.

PMID- 23562046
TI  - In vitro fertilization-intracytoplasmic sperm injection outcome in patients with
      a markedly high DNA fragmentation index (>50%).
AB  - OBJECTIVE: To investigate differences in fertilization, clinical pregnancy, and
      miscarriage rates between men with a markedly high sperm DNA fragmentation index
      (DFI) (>50%) and those with low DFI (<= 15%) in couples matched by female partner
      age and ovarian reserve as determined by antimullerian hormone (AMH) level.
      DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility
      center. PATIENT(S): Men undergoing intracytoplasmic sperm injection (ICSI) cycles
      who had low (n = 114) or markedly high (n = 36) DNA damage. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Sperm DNA damage evaluated by acridine orange flow
      cytometry and expressed as the DFI, with the potential confounders of ovarian
      reserve and age controlled for by multivariable logistic regression analysis.
      RESULT(S): The fertilization and clinical pregnancy rates were not different
      between the two groups. We observed a trend toward a higher miscarriage rate with
      the high DFI group, but it did not reach statistical significance. CONCLUSION(S):
      Intracytoplasmic sperm injection in men with a high DFI with sperm selected by
      movement and morphology characteristics resulted in a similar pregnancy rate
      compared with the controls with a normal DFI. However, the trend observed of an
      increase in miscarriages suggests that any potential negative impact may appear
      later in development. Future studies involving a larger cohort may determine if
      the miscarriage trend reaches statistical significance.

PMID- 23562047
TI  - Targeting CCL21-folic acid-upconversion nanoparticles conjugates to folate
      receptor-alpha expressing tumor cells in an endothelial-tumor cell bilayer model.
AB  - The ability of some malignant cells to evade immunosurveillance has been a major
      contribution to the inability of the host's immune system to eradicate the
      neoplastic cells. This has led to the development of various immunological
      strategies to augment the host immune response as part of cancer treatment. In
      this study, we developed folic acid (FA)/secondary lymphoid tissue chemokine
      (CCL21)/upconversion fluorescent nanoparticles (UCNs) conjugates as a targeting
      and delivery system to attract immune cells to folate receptor (FR) expressing
      tumor cells. Our data show that FA-conjugated UCNs@mesoporous silica specifically
      target FR expressing ovarian carcinoma cell line, OVCAR-3, compared to the
      unconjugated mesoporous silica coated UCNs. Furthermore, the FA-UCNs@mesoporous
      silica can efficiently cross the endothelial cell monolayer and accumulate in the
      clusters of OVCAR-3 cells in our endothelial-tumor cell bilayer model. Our
      migration assay data suggest that the CCL21 loaded into the mesoporous layer is
      biologically active and can efficiently induce T cells migration in-vitro. No
      significant cytotoxic effect was observed throughout the study indicating good
      biocompatibility of the nanoconjugates. As proof-of-concept, we have shown that
      it is feasible to load biologically active chemokines onto UCNs to modulate T
      cell migration.

PMID- 23562048
TI  - A bioengineered microenvironment to quantitatively measure the tumorigenic
      properties of cancer-associated fibroblasts in human prostate cancer.
AB  - Stromal-epithelial cell interactions play an important role in cancer and the
      tumor stroma is regarded as a therapeutic target. In vivo xenografting is
      commonly used to study cellular interactions not mimicked or quantified in
      conventional 2D culture systems. To interrogate the effects of tumor stroma
      (cancer-associated fibroblasts or CAFs) on epithelia, we created a bioengineered
      microenvironment using human prostatic tissues. Patient-matched CAFs and non
      malignant prostatic fibroblasts (NPFs) from men with moderate (Gleason 7) and
      aggressive (Gleason 8-9 or castrate-resistant) prostate cancer were cultured with
      non-tumorigenic BPH-1 epithelial cells. Changes in the morphology, motility and
      phenotype of BPH-1 cells in response to CAFs and NPFs were analyzed using
      immunofluorescence and quantitative cell morphometric analyses. The matrix
      protein gene expression of CAFs, with proven tumorigenicity in vivo, had a
      significantly different gene expression profile of matrix proteins compared to
      patient matched NPFs. In co-culture with CAFs (but not NPFs), BPH-1 cells had a
      more invasive, elongated phenotype with increased motility and a more directed
      pattern of cell migration. CAFs from more aggressive tumors (Gleason 8-9 or CRPC)
      were not quantitatively different to moderate grade CAFs. Overall, our
      bioengineered microenvironment provides a novel 3D in vitro platform to
      systematically investigate the effects of tumor stroma on prostate cancer
      progression.

PMID- 23562049
TI  - Probing structure-antifouling activity relationships of polyacrylamides and
      polyacrylates.
AB  - We have synthesized two different polyacrylamide polymers with amide groups
      (polySBAA and polyHEAA) and two corresponding polyacrylate polymers without amide
      groups (polySBMA and polyHEA), with particular attention to the evaluation of the
      effect of amide group on the hydration and antifouling ability of these systems
      using both computational and experimental approaches. The influence of polymer
      architectures of brushes, hydrogels, and nanogels, prepared by different
      polymerization methods, on antifouling performance is also studied. SPR and ELISA
      data reveal that all polymers exhibit excellent antifouling ability to repel
      proteins from undiluted human blood serum/plasma, and such antifouling ability
      can be further enhanced by presenting amide groups in polySBAA and polyHEAA as
      compared to polySBMA and polyHEA. The antifouling performance is positively
      correlated with the hydration properties. Simulations confirm that four polymers
      indeed have different hydration characteristics, while all presenting a strong
      hydration overall. Integration of amide group with pendant hydroxyl or
      sulfobetaine group in polymer backbones is found to increase their surface
      hydration of polymer chains and thus to improve their antifouling ability.
      Importantly, we present a proof-of-concept experiment to synthesize polySBAA
      nanogels, which show a switchable property between antifouling and pH-responsive
      functions driven by acid-base conditions, while still maintaining high stability
      in undiluted fetal bovine serum and minimal toxicity to cultured cells. This work
      provides important structural insights into how very subtle structural changes in
      polymers can yield great improvement in biological activity, specifically the
      inclusion of amide group in polymer backbone/sidechain enables to obtain
      antifouling materials with better performance for biomedical applications.

PMID- 23562050
TI  - Potent killing of HBV-related hepatocellular carcinoma by a chimeric protein of
      anti-HBsAg single-chain antibody and truncated Bid.
AB  - Targeted therapy is needed for hepatitis B virus (HBV)-mediated hepatocellular
      carcinoma (HCC) which shows overexpression of HBV surface antigen (HBsAg). We
      previously developed scFv15, a human single-chain antibody against HBsAg. Here we
      tested the strategic feasibility of scFv15-mediated delivery of apoptotic
      effectors for HBsAg-targeted HCC therapy and application of HA2 motif of
      influenza hemagglutinin to enhance endosome escape and antitumor effect. A class
      of HBsAg-targeted immunoproapoptotic molecule was generated by sequentially
      fusing scFv15, the furin-cleavable motif from diphtheria toxin (Fdt), HA2 and a
      truncated apoptotic protein Bid (tBid). The resulting scFv15-Fdt-HA2-tBid was
      prokaryotically expressed and functionally characterized for HBsAg-binding
      capacity, endosome escape activity and antitumor effect as compared with scFv15
      Fdt-tBid. Both scFv15-Fdt-HA2-tBid and scFv15-Fdt-tBid retained affinity and
      specificity for HBsAg, and bound and selectively killed HBsAg-positive HCC cells
      via apoptosis. Notably, the IC50 of scFv15-Fdt-HA2-tBid in HBsAg-positive
      PLC/PRF/5 cells was 10 times lower than that of scFv15-Fdt-tBid. In vivo imaging
      of antitumor activity demonstrated 95% growth inhibition of orthotopic HCC by
      scFv15-Fdt-HA2-tBid compared with 75% suppression by scFv15-Fdt-tBid. This study
      represents an extended application of the immunoproapoptotic strategy in the
      treatment of HBsAg-positive HCC and shows significant potential of HA2 as a
      functional enhancer for endosome-encapsulated antibody-conjugates.

PMID- 23562051
TI  - Substrate-dependent Wnt signaling in MSC differentiation within biomaterial
      derived 3D spheroids.
AB  - A unique biomaterial-based system was developed to generate dynamic three
      dimensional (3D) multicellular spheroids of mesenchymal stem cells (MSCs). MSCs
      were cultured on transparent membranes made of chitosan or those further grafted
      with hyaluronan (HA) in different densities. MSCs vigorously migrated and were
      self-assembled into highly mobile 3D spheroids with substrate-dependent
      upregulation of adhesion molecule N-cadherin. MSC spheroids showed increased
      expression of Wnt genes/proteins and substrate-dependent cell fate. The
      correlation of differentiation capacities with Wnt signaling and crosstalk with
      other pathways such as ERK1/2 or Smad2/3 were observed for MSC spheroids but not
      for the conventional 2D cultured cells. Wnt3a-mediated canonical Wnt signaling
      was more active for MSC spheroids derived on chitosan, which were prone to
      osteogenesis. Wnt5a-mediated non-canonical Wnt signaling was more active for MSC
      spheroids derived on HA-grafted chitosan, which were prone to chondrogenesis. In
      particular, the relative importance of Wnt5a-mediated non-canonical vs. Wnt3a
      mediated canonical Wnt signals in determining the cell fate was controlled by the
      grafting density of HA on chitosan. Treatment with the inhibitor of canonical Wnt
      associated signaling molecules suppressed the osteogenesis of MSC spheroids on
      chitosan. This study demonstrates that Wnt signaling of MSCs is distinct in 3D
      environment and is substrate-dependent. The convenient 3D platform may be used to
      examine the role of Wnt signaling in controlling MSC fate under different
      extracellular environments, and potentially applied to study stem cell behavior
      in regenerative medicine, normal development, and cancer.

PMID- 23562052
TI  - Tuning supramolecular mechanics to guide neuron development.
AB  - The mechanical properties of the extracellular matrix (ECM) are known to
      influence neuronal differentiation and maturation, though the mechanism by which
      neuronal cells respond to these biophysical cues is not completely understood.
      Here we design ECM mimics using self-assembled peptide nanofibers, in which fiber
      rigidity is tailored by supramolecular interactions, in order to investigate the
      relationship between matrix stiffness and morphological development of
      hippocampal neurons. We observe that development of neuronal polarity is
      accelerated on soft nanofiber substrates, and results from the dynamics of
      neuronal processes. While the total neurite outgrowth of non-polar neurons
      remains conserved, weaker adhesion of neurites to soft PA substrate facilitates
      easier retraction, thus enhancing the frequency of "extension-retraction" events.
      We hypothesize that higher neurite motility enhances the probability of one
      neurite to reach a critical length relative to others, thereby initiating the
      developmental sequence of axon differentiation. Our results suggest that
      substrate stiffness can influence neuronal development by regulating its
      dynamics, thus providing useful information on scaffold design for applications
      in neural regeneration.

PMID- 23562053
TI  - The impact of chronic blood-brain barrier breach on intracortical electrode
      function.
AB  - Brain-computer interfaces (BCIs) have allowed control of prosthetic limbs in
      paralyzed patients. Unfortunately, the electrodes of the BCI that interface with
      the brain only function for a short period of time before the signal quality on
      these electrodes becomes substantially diminished. To truly realize the potential
      of BCIs, it is imperative to have electrodes that function chronically. In order
      to elucidate the physiological determinants of a chronically functional neural
      interface, we studied the role of the blood-brain barrier (BBB) in electrode
      function, because it is a key mediator of neuronal hemostasis. We monitored the
      status of the BBB and the consequences of BBB breach on electrode function using
      non-invasive imaging, electrophysiology, genomic, and histological analyses. Rats
      implanted with commercially available intracortical electrodes demonstrated an
      inverse correlation between electrode performance and BBB breach over a period of
      16 weeks. Genomic analysis showed that chronically functional electrodes elicit
      an enhanced wound healing response. Conversely, in poorly functioning electrodes,
      chronic BBB breach led to local accumulation of neurotoxic factors and an influx
      of pro-inflammatory myeloid cells, which negatively affect neuronal health. These
      findings were further verified in a subset of electrodes with graded
      electrophysiological performance. In this study, we determine the mechanistic
      link between intracortical electrode function and failure. Our results indicate
      that BBB status is a critical physiological determinant of intracortical
      electrode function and can inform future electrode design and biochemical
      intervention strategies to enhance the functional longevity of BCIs.

PMID- 23562055
TI  - Isoniazid: Radical-induced oxidation and reduction chemistry.
AB  - Isoniazid is a potent and selective therapeutic prodrug agent used to treat
      infections by Mycobacterium tuberculosis. Although it has been used clinically
      for over five decades its full mechanism of action is still being elucidated.
      Essential to its mechanism of action is the activation of isoniazid to a reactive
      intermediate, the isonicotinyl acyl radical, by the catalase-peroxidase KatG. The
      isonicotinyl acyl radical then reacts with NAD producing an inhibitor of the NADH
      dependent enoyl ACP reductase responsible for mycolic acid synthesis as its
      primary target. However, the initial oxidation of isoniazid by KatG has also
      revealed alternative reaction pathways leading to an array of carbon-, oxygen-,
      and nitrogen-centered radical intermediates. It has also been reported that
      isoniazid produces nitric oxide in the presence of KatG and hydrogen peroxide. In
      this study, the temperature-dependent rate constants for the hydroxyl radical
      oxidation and solvated electron reduction of isoniazid and two model compounds
      have been studied. Based on these data the initial oxidation of isoniazid by the
      hydroxyl radical has been shown to predominantly occur at the primary nitrogen of
      the hydrazyl moiety, consistent with the postulated mechanism for the formation
      of the isonicotinyl radical. The hydrated electron reduction occurred mostly at
      the pyridine ring. Concomitant EPR spin-trap measurements under a variety of
      oxidizing and reducing conditions did not show any evidence of nitric oxide
      production as had been previously reported. Finally, examination of the transient
      absorption spectra obtained for hydrated electron reaction with isoniazid
      demonstrated for the first time an initial reduced transient identified as the
      isonicotinyl acyl radical produced from isoniazid.

PMID- 23562054
TI  - Anti-HIV efficacy and biodistribution of nucleoside reverse transcriptase
      inhibitors delivered as squalenoylated prodrug nanoassemblies.
AB  - Due to their hydrophilic nature, most nucleoside reverse transcriptase inhibitors
      (NRTIs) display a variable bioavailability after oral administration and a poor
      control over their biodistribution, thus hampering their access to HIV
      sanctuaries. The limited cellular uptake and activation in the triphosphate form
      of NRTIs further restrict their efficacy and favour the emergence of viral
      resistance. We have shown that the conjugation of squalene (sq) to the nucleoside
      analogues dideoxycytidine (ddC) and didanosine (ddI) leads to amphiphilic
      prodrugs (ddC-sq and ddI-sq) that spontaneously self-organize in water as stable
      nanoassemblies of 100-300 nm. These nanoassemblies can also be formulated with
      polyethylene glycol coupled to either cholesterol (Chol-PEG) or squalene (sq
      PEG). When incubated with peripheral blood mononuclear cells (PBMCs) in vitro
      infected with HIV, the NRTI-sq prodrugs enhanced the antiviral efficacy of the
      parent NRTIs, with a 2- to 3-fold decrease of the 50% effective doses and a
      nearly 2-fold increase of the selectivity index. This was also the case with HIV
      1 strains resistant to ddC and/or ddI. The enhanced antiviral activity of ddI-sq
      was correlated with an up to 5-fold increase in the intracellular concentration
      of the corresponding pharmacologically active metabolite ddA-TP. The ddI-sq
      prodrug was further investigated in vivo by the oral route, the preferred route
      of administration of NRTIs. Pharmacokinetics studies performed on rats showed
      that the prodrug maintained low amounts of free ddI in the plasma. Administration
      of (3)H-ddI-sq led to radioactivity levels higher in the plasma and relevant
      organs in HIV infection as compared to administration of free (3)H-ddI. Taken
      together, these results show the potential of the squalenoylated prodrugs of
      NRTIs to enhance their absorption and improve their biodistribution, but also to
      enhance their intracellular delivery and antiviral efficacy towards HIV-infected
      cells.

PMID- 23562056
TI  - Conformational restriction approach to BACE1 inhibitors II: SAR study of the
      isocytosine derivatives fixed with a cis-cyclopropane ring.
AB  - To improve the efficacy of the conformationally restricted BACE1 inhibitors,
      structural modifications were investigated using two strategies: (a) modification
      of the terminal aromatic ring and (b) insertion of a spacer between the aromatic
      rings. In the latter approach, another type of inhibitor 17 bearing an ethylene
      spacer between two aromatic rings was found to exhibit good BACE1 inhibitory
      activity, while the corresponding conformationally unrestricted compound 25
      showed no activity. This result revealed an interesting effect of a
      conformational restriction with a cyclopropane ring.

PMID- 23562057
TI  - Structure-based design of HSPA5 inhibitors: from peptide to small molecule
      inhibitors.
AB  - We identified nine small-molecule hit compounds of Heat shock 70kDa protein 5
      (HSPA5) from cascade in silico screening based on the binding modes of the
      tetrapeptides derived from the peptide substrate or inhibitors of Escherichia
      coli HSP70. Two compounds exhibit promising inhibition activities from cancer
      cell viability and tumor inhibition assays. The binding modes of the hit
      compounds provide a platform for development of selective small molecule
      inhibitors of HSPA5.

PMID- 23562058
TI  - Voulkensin C-E, new 11-oxocassane-type diterpenoids and a steroid glycoside from
      Caesalpinia volkensii stem bark and their antiplasmodial activities.
AB  - A bioassay guided isolation of potential antimalarial molecules from the stem
      bark of Caesalpinia volkensii Harms (Fabaceae) achieved three new 11-oxocassane
      type diterpenoids named voulkensin C (1), D (2) and E (3) together with one
      steroid glycoside named 3-O-[beta-glucopyranosyl(1->2)-O-beta-xylopyranosyl]
      stigmasterol (4) and seven other known compounds including stigmasterol (5), beta
      sitosterol (6), oleanolic acid (7), 3-beta-acetoxyolean-12-en-28-methyl ester
      (8), voucap-5-ol (9), caesadekarin C (10), deoxycaesaldekarin C (11). The
      structures of the new compounds were determined on the basis of extensive
      spectroscopic data (IR, MS, (1)H and (13)C NMR and 2D NMR) analyses. The polar
      extracts revealed moderate to good antiplasmodial activities against chloquine
      sensitive (D6) and -resistant strains (W2) of Plasmodium falciparum. Whereas the
      pure isolates exhibited limited to moderate antiplasmodial activities with
      compound 4 showing the highest antiplasmodial activities (IC50 values of 4.44+/
      0.88 and 2.74+/-1.10MUM against D6 and W2 strains, respectively). These results
      suggest a possible contribution of phytochemicals from C. volkensii stem bark
      towards inhibition of plasmodial parasites' growth hence potential antimalarial.

PMID- 23562059
TI  - Design, synthesis and evaluation of some new 4-aminopyridine derivatives in
      learning and memory.
AB  - Some new anilide and imide derivatives of 4-aminopyridine (4AP) were synthesized
      and evaluated against antiamnesic, cognition enhancing and anticholinesterase
      activity through their respective in vitro and in vivo models. These newly
      synthesized derivatives have illustrated an enhanced cognition effect on elevated
      plus maze model and also demonstrated a significant reversal in scopolamine
      induced amnesia in same model. The IC50 value of synthesized compounds showed
      maximum activity of 4APMb compared to standard drug donepezil and other
      derivatives, whereas its enzyme kinetic study revealed a non-competitive
      inhibition of acetycholinesterase (AChE) and a competetive inhibition of
      butyrylcholinesterase (BChE). Significant inhibitions in AChE activity by all the
      synthesized compounds were found in specific brain regions that is prefrontal
      cortex, hippocampus and hypothalamus. The docking study confirmed their
      consensual interaction with AChE, showed an affinity and binding with the key
      peripheral anionic site residues Trp-286, Tyr-124 and Tyr-341 of AChE.

PMID- 23562060
TI  - Discovery of ML326: The first sub-micromolar, selective M5 PAM.
AB  - This Letter describes the further chemical optimization of the M5 PAM MLPCN
      probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort
      quickly explored isatin replacements and a number of southern heterobiaryl
      variations with no improvement over ML129 and ML172. An HTS campaign identified
      several weak M5 PAMs (M5 EC50 >10MUM) with a structurally related isatin core
      that possessed a southern phenethyl ether linkage. While SAR within the HTS
      series was very shallow and unable to be optimized, grafting the phenethyl ether
      linkage onto the ML129/ML172 cores led to the first sub-micromolar M5 PAM, ML326
      (VU0467903), (human and rat M5 EC50s of 409nM and 500nM, respectively) with
      excellent mAChR selectivity (M1-M4 EC50s >30MUM) and a robust 20-fold leftward
      shift of the ACh CRC.

PMID- 23562061
TI  - Ostreol A: a new cytotoxic compound isolated from the epiphytic dinoflagellate
      Ostreopsis cf. ovata from the coastal waters of Jeju Island, Korea.
AB  - Ostreol A was isolated from cultures of the epiphytic dinoflagellate Ostreopsis
      cf. ovata from the coastal waters of Jeju Island, Korea. The compound, a non
      palytoxin derivative, has a polyhydroxy chain ending with the primary amino group
      and contains an amide bond, along with two tetrahydropyran rings in the chain.
      Its chemical structure was elucidated by nuclear magnetic resonance (NMR)
      spectroscopy methods and confirmed by mass analysis. The compound exhibited
      significant cytotoxicity in the brine shrimp lethality test at a concentration of
      0.9MUg/mL.

PMID- 23562062
TI  - Arylsulfonamide pyrimidines as VLA-4 antagonists.
AB  - A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)
      3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4
      antagonists. Representative compounds 11b and 11p showed efficacy in multiple in
      vivo animal models. The in vitro selectivity of 11p is also described.

PMID- 23562063
TI  - The design and synthesis of a potent glucagon receptor antagonist with favorable
      physicochemical and pharmacokinetic properties as a candidate for the treatment
      of type 2 diabetes mellitus.
AB  - A novel and potent small molecule glucagon receptor antagonist for the treatment
      of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4
      (trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has
      lower molecular weight and lipophilicity than historical glucagon receptor
      antagonists, resulting in excellent selectivity in broad-panel screening, lower
      cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing.
      Additionally, it displays low in vivo clearance and excellent oral
      bioavailability in both rats and dogs. In a rat glucagon challenge model, it was
      shown to reduce the glucagon-elicited glucose excursion in a dose-dependent
      manner and at a concentration consistent with its rat in vitro potency. Its
      properties make it an excellent candidate for further investigation.

PMID- 23562064
TI  - Mutual interaction between human multipotent adult progenitor cells and NK cells.
AB  - Human multipotent adult progenitor cells (hMAPCs) are isolated from bone marrow
      with a more extensive expansion capacity compared to human mesenchymal stem cells
      (hMSCs) and with the ability to differentiate into endothelium. Like hMSCs,
      hMAPCs inhibit T-cell proliferation induced by alloantigens. In this study, we
      tested the interaction between hMAPCs and natural killer (NK) cells. We assessed
      the susceptibility of hMAPCs to NK cell-mediated lysis and the immunomodulation
      of hMAPCs on NK cell function during IL-2-driven stimulation and the cytolytic
      effector phase. Human MAPCs express the ligands PVR and ULBP-2/5/6, which are
      recognized by activating NK cell receptors. However, they also express MHC class
      I molecules, which induce inhibitory signals in NK cells. Freshly isolated NK
      cells at different effector:target ratios did not kill hMAPCs as assessed by an
      MTT and (51)Cr-release assay, while hMAPCs impaired the cytotoxic activity of
      resting NK cells against the NK-sensitive K562 leukemia cell line. By contrast,
      IL-2-stimulated NK cells were capable of killing hMAPCs, and preactivated NK
      cells were not influenced during their cytotoxic effector function against K562
      cells by hMAPCs. When added during the 6-day preactivation phase with IL-2,
      hMAPCs dose-dependently reduced NK cell proliferation in an IDO-dependent manner,
      but they did not influence the induction of cytotoxic capacity by IL-2. This
      study indicates that human MAPCs mutually interact with NK cells. 

PMID- 23562065
TI  - Cathodal transcranial direct current stimulation affects seizures and cognition
      in fully amygdala-kindled rats.
AB  - This study evaluated the effects of weak transcranial direct current stimulation
      (tDCS), a new non-invasive brain stimulation technique, on amygdala-kindled rats.
      The seizure severity, i.e. seizure stage, afterdischarge duration (ADD), and AD
      threshold (ADT) in the animals were measured one day after the last cathodal tDCS
      session, comparing with those of pre-treatment controls. Furthermore, the effects
      of cathodal tDCS on cognitive function were also studied by a water maze test
      (WMT) two days after the last tDCS session. Cathodal tDCS treatment significantly
      improved the seizure stage and decreased ADD together with elevated ADT one day
      after the last tDCS session. The treatment also showed significant improvement in
      the performance of WMT. The findings suggest that cathodal tDCS has
      anticonvulsive after-effects last at least for one day on the amygdala-kindled
      rats and positively affects cognitive performance.

PMID- 23562066
TI  - Evaluation of the ESRS and SPI-II scales for short-term prognosis of minor stroke
      and transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Rapid evaluation of stroke risk following an initial
      stroke may improve patient outcome, especially in cases of minor stroke. We
      investigated the validity of the Essen stroke risk score (ESRS) and stroke
      prognosis instrument II (SPI-II) scales for predicting the short-term risk of
      minor stroke and transient ischemic attack (TIA) in the clinic. METHODS: One
      hundred and sixty-seven patients with minor stroke or TIA were enrolled in this
      study. The recurrent ischemic events were recorded within 90 days after the
      initial onset and the curve of cumulative survival rate was calculated to observe
      the recurrence risk. The prognostic value of the ESRS and SPI-II scales for
      recurrence risk were evaluated by calculating the area under receiver operating
      characteristic (ROC) curve. RESULTS: The total recurrence rate of ischemic events
      within 90 days was 12.57% while the recurrence rate was 7.78% in the first week
      after onset. Remarkable change was observed on the curve of cumulative survival
      rate during the acute phase of stroke. The area under the ROC curve of the ESRS
      scale was 0.677 (95% CI: 0.557-0.797) compared to 0.553 (95% CI: 0.413-0.694) of
      the SPI-II scale. CONCLUSION: The ESRS and SPI-II scales can be used as screening
      tools to evaluate the short-term risk for recurrent events of minor stroke and
      TIA. Importantly, the ESRS was more suitable for predicting the short-term risk
      of stroke in the clinic.

PMID- 23562067
TI  - Treatment of a complex tracheobronchial malignant stenosis with a modified
      conical semicovered self-expanding stent.

PMID- 23562068
TI  - Hemoconcentration in ex vivo lung perfusion: a case report of a novel technique
      used in clinical lung transplantation.

PMID- 23562069
TI  - Three-dimensional segmentation of the left ventricle in late gadolinium enhanced
      MR images of chronic infarction combining long- and short-axis information.
AB  - Automatic segmentation of the left ventricle (LV) in late gadolinium enhanced
      (LGE) cardiac MR (CMR) images is difficult due to the intensity heterogeneity
      arising from accumulation of contrast agent in infarcted myocardium. In this
      paper, we present a comprehensive framework for automatic 3D segmentation of the
      LV in LGE CMR images. Given myocardial contours in cine images as a priori
      knowledge, the framework initially propagates the a priori segmentation from cine
      to LGE images via 2D translational registration. Two meshes representing
      respectively endocardial and epicardial surfaces are then constructed with the
      propagated contours. After construction, the two meshes are deformed towards the
      myocardial edge points detected in both short-axis and long-axis LGE images in a
      unified 3D coordinate system. Taking into account the intensity characteristics
      of the LV in LGE images, we propose a novel parametric model of the LV for
      consistent myocardial edge points detection regardless of pathological status of
      the myocardium (infarcted or healthy) and of the type of the LGE images (short
      axis or long-axis). We have evaluated the proposed framework with 21 sets of real
      patient and four sets of simulated phantom data. Both distance- and region-based
      performance metrics confirm the observation that the framework can generate
      accurate and reliable results for myocardial segmentation of LGE images. We have
      also tested the robustness of the framework with respect to varied a priori
      segmentation in both practical and simulated settings. Experimental results show
      that the proposed framework can greatly compensate variations in the given a
      priori knowledge and consistently produce accurate segmentations.

PMID- 23562070
TI  - How is the hungry brain like a sieve?
AB  - Whether some hypothalamic neurons have direct access to circulating metabolic
      cues represents a crucial question that has been intensely debated. New findings
      reveal that fasting promotes "leakiness" of some hypothalamic blood vessels,
      increasing the access of circulating factors to certain hypothalamic neurons that
      control feeding (Langlet et al., 2013).

PMID- 23562071
TI  - Insulin and ventral tegmental dopamine: what's impaired and what's intact?
AB  - Manipulations affecting mesolimbic dopamine transmission exert specific effects
      on normal and pathological aspects of motivation, altering some functions while
      sparing others. Labouebe et al. (2013) show that insulin induced long-term
      depression in ventral tegmental neurons, which was associated with reduced
      responsiveness to food-related stimuli but spared aspects of food-seeking
      behavior.

PMID- 23562072
TI  - Altered cholesterol homeostasis in aged macrophages linked to neovascular macular
      degeneration.
AB  - Abnormal lipid metabolism has been linked to age-related macular degeneration
      (AMD); choroidal neovascularization in late AMD commonly causes blindness. Sene
      et al. (2013) now demonstrate that in aged macrophages decreased ABCA1
      expression, regulated by liver X receptor and miR-33, impairs export of
      intracellular cholesterol, which promotes neovascular AMD.

PMID- 23562073
TI  - Raggin' on T-bet.
AB  - Although increasing adiposity is usually associated with adipose tissue
      infiltration by inflammatory cells and systemic insulin resistance, Stolarczyk et
      al. (2013) report in this issue that mice deficient in the T-box transcription
      factor, T-bet, display a dissociated phenotype with enhanced perigonadal adipose
      but enhanced insulin sensitivity.

PMID- 23562074
TI  - The endocannabinoid system in energy homeostasis and the etiopathology of
      metabolic disorders.
AB  - Endocannabinoids and cannabinoid CB1 receptors are known to play a generalized
      role in energy homeostasis. However, clinical trials with the first generation of
      CB1 blockers, now discontinued due to psychiatric side effects, were originally
      designed to reduce food intake and body weight rather than the metabolic risk
      factors associated with obesity. In this review, we discuss how, in addition to
      promoting energy intake, endocannabinoids control lipid and glucose metabolism in
      several peripheral organs, particularly the liver and adipose tissue. Direct
      actions in skeletal muscle and pancreas are also emerging. This knowledge may
      help in the design of future therapies for the metabolic syndrome.

PMID- 23562076
TI  - Improved insulin sensitivity despite increased visceral adiposity in mice
      deficient for the immune cell transcription factor T-bet.
AB  - Low-grade inflammation in fat is associated with insulin resistance, although the
      mechanisms are unclear. We report that mice deficient in the immune cell
      transcription factor T-bet have lower energy expenditure and increased visceral
      fat compared with wild-type mice, yet paradoxically are more insulin sensitive.
      This striking phenotype, present in young T-bet(-/-) mice, persisted with high
      fat diet and increasing host age and was associated with altered immune cell
      numbers and cytokine secretion specifically in visceral adipose tissue. However,
      the favorable metabolic phenotype observed in T-bet-deficient hosts was lost in T
      bet(-/-) mice also lacking adaptive immunity (T-bet(-/-)xRag2(-/-)),
      demonstrating that T-bet expression in the adaptive rather than the innate immune
      system impacts host glucose homeostasis. Indeed, adoptive transfer of T-bet
      deficient, but not wild-type, CD4(+) T cells to Rag2(-/-) mice improved insulin
      sensitivity. Our results reveal a role for T-bet in metabolic physiology and
      obesity-associated insulin resistance.

PMID- 23562075
TI  - Mitochondrial dynamics in the regulation of nutrient utilization and energy
      expenditure.
AB  - Mitochondrial fusion, fission, and mitophagy form an essential axis of
      mitochondrial quality control. However, quality control might not be the only
      task carried out by mitochondrial dynamics. Recent studies link mitochondrial
      dynamics to the balance between energy demand and nutrient supply, suggesting
      changes in mitochondrial architecture as a mechanism for bioenergetic adaptation
      to metabolic demands. By favoring either connected or fragmented architectures,
      mitochondrial dynamics regulates bioenergetic efficiency and energy expenditure.
      Placement of bioenergetic adaptation and quality control as competing tasks of
      mitochondrial dynamics might provide a new mechanism, linking excess nutrient
      environment to progressive mitochondrial dysfunction, common to age-related
      diseases.

PMID- 23562077
TI  - Imbalance between neutrophil elastase and its inhibitor alpha1-antitrypsin in
      obesity alters insulin sensitivity, inflammation, and energy expenditure.
AB  - The molecular mechanisms involved in the development of obesity and related
      complications remain unclear. Here, we report that obese mice and human subjects
      have increased activity of neutrophil elastase (NE) and decreased serum levels of
      the NE inhibitor alpha1-antitrypsin (A1AT, SerpinA1). NE null (Ela2(-/-)) mice
      and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body
      weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor
      GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2(
      /-) mice also augmented circulating high molecular weight (HMW) adiponectin
      levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid
      oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling
      protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system
      regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT
      and NE contributes to the development of obesity and related inflammation,
      insulin resistance, and liver steatosis.

PMID- 23562078
TI  - Impaired cholesterol efflux in senescent macrophages promotes age-related macular
      degeneration.
AB  - Pathologic angiogenesis mediated by abnormally polarized macrophages plays a
      central role in common age-associated diseases such as atherosclerosis, cancer,
      and macular degeneration. Here we demonstrate that abnormal polarization in older
      macrophages is caused by programmatic changes that lead to reduced expression of
      ATP binding cassette transporter ABCA1. Downregulation of ABCA1 by microRNA-33
      impairs the ability of macrophages to effectively efflux intracellular
      cholesterol, which in turn leads to higher levels of free cholesterol within
      senescent macrophages. Elevated intracellular lipid polarizes older macrophages
      to an abnormal, alternatively activated phenotype that promotes pathologic
      vascular proliferation. Mice deficient for Abca1, but not Abcg1, demonstrate an
      accelerated aging phenotype, whereas restoration of cholesterol efflux using LXR
      agonists or miR-33 inhibitors reverses it. Monocytes from older humans with age
      related macular degeneration showed similar changes. These findings provide an
      avenue for therapeutic modulation of macrophage function in common age-related
      diseases.

PMID- 23562079
TI  - Molecular and genetic crosstalks between mTOR and ERRalpha are key determinants
      of rapamycin-induced nonalcoholic fatty liver.
AB  - mTOR and ERRalpha are key regulators of common metabolic processes, including
      lipid homeostasis. However, it is currently unknown whether these factors
      cooperate in the control of metabolism. ChIP-sequencing analyses of mouse liver
      reveal that mTOR occupies regulatory regions of genes on a genome-wide scale
      including enrichment at genes shared with ERRalpha that are involved in the TCA
      cycle and lipid biosynthesis. Genetic ablation of ERRalpha and rapamycin
      treatment, alone or in combination, alter the expression of these genes and
      induce the accumulation of TCA metabolites. As a consequence, both genetic and
      pharmacological inhibition of ERRalpha activity exacerbates hepatic
      hyperlipidemia observed in rapamycin-treated mice. We further show that mTOR
      regulates ERRalpha activity through ubiquitin-mediated degradation via
      transcriptional control of the ubiquitin-proteasome pathway. Our work expands the
      role of mTOR action in metabolism and highlights the existence of a potent
      mTOR/ERRalpha regulatory axis with significant clinical impact.

PMID- 23562081
TI  - MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand
      promoter but is dispensable for rRNA gene transcription regulation.
AB  - Mitochondrial transcription termination factor 1, MTERF1, has been reported to
      couple rRNA gene transcription initiation with termination and is therefore
      thought to be a key regulator of mammalian mitochondrial ribosome biogenesis. The
      prevailing model is based on a series of observations published over the last two
      decades, but no in vivo evidence exists to show that MTERF1 regulates
      transcription of the heavy-strand region of mtDNA containing the rRNA genes.
      Here, we demonstrate that knockout of Mterf1 in mice has no effect on
      mitochondrial rRNA levels or mitochondrial translation. Instead, loss of Mterf1
      influences transcription initiation at the light-strand promoter, resulting in a
      decrease of de novo transcription manifested as reduced 7S RNA levels. Based on
      these observations, we suggest that MTERF1 does not regulate heavy-strand
      transcription, but rather acts to block transcription on the opposite strand of
      mtDNA to prevent transcription interference at the light-strand promoter.

PMID- 23562080
TI  - Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of
      metabolic signals to the arcuate nucleus in response to fasting.
AB  - The delivery of blood-borne molecules conveying metabolic information to neural
      networks that regulate energy homeostasis is restricted by brain barriers. The
      fenestrated endothelium of median eminence microvessels and tight junctions
      between tanycytes together compose one of these. Here, we show that the decrease
      in blood glucose levels during fasting alters the structural organization of this
      blood-hypothalamus barrier, resulting in the improved access of metabolic
      substrates to the arcuate nucleus. These changes are mimicked by 2-deoxyglucose
      induced glucoprivation and reversed by raising blood glucose levels after
      fasting. Furthermore, we show that VEGF-A expression in tanycytes modulates these
      barrier properties. The neutralization of VEGF signaling blocks fasting-induced
      barrier remodeling and significantly impairs the physiological response to
      refeeding. These results implicate glucose in the control of blood-hypothalamus
      exchanges through a VEGF-dependent mechanism and demonstrate a hitherto
      unappreciated role for tanycytes and the permeable microvessels associated with
      them in the adaptive metabolic response to fasting.

PMID- 23562082
TI  - Beyond the pineal gland assumption: a neuroanatomical appraisal of dualism in
      Descartes' philosophy.
AB  - OBJECTIVE: The problem of the substantial union of the soul and the body and
      therefore the mechanisms of interaction between them represents the core of the
      Cartesian dualistic philosophy. This philosophy is based upon a neuroanatomical
      obvious misconception, consisting mainly on a wrong intraventricular position of
      the pineal gland and its capacity of movement to act as a valve regulating the
      flow of animal spirits. Should we consider the Cartesian neurophysiology as a
      purely anatomical descriptive work and therefore totally incorrect, or rather as
      a theoretical conception supporting his dualistic philosophy? METHOD: From the
      various pre-Cartesian theories on the pineal organ, we try to explain how
      Descartes used his original conception of neuroanatomy to serve his dualistic
      philosophy. Moreover, we present an appraisal of the Cartesian neuroanatomical
      corpus from an anatomical but also metaphysical and theological perspectives.
      RESULTS: A new interpretation of Descartes' writings and an analysis of the
      secondary related literature shed the light on the voluntary anatomical
      approximations aiming to build an ad hoc neurophysiology that allows Descartes'
      soul-body theory. CONCLUSION: By its central position within the brain mass and
      its particular shape, the pineal gland raised diverse metaphysical theories
      regarding its function, but the most original theory remains certainly its role
      as the seat of soul in Rene Descartes' philosophy and more precisely the organ
      where soul and body interact. The author emphasizes on the critics raised by
      Descartes' theories on the soul-body interaction through the role of the pineal
      gland.

PMID- 23562084
TI  - Twenty-five years of fetal echocardiography in conjoined twins: lessons learned.
AB  - BACKGROUND: The aim of this study was to determine the accuracy of prenatal
      echocardiography in the diagnosis of intracardiac malformations and the degree of
      cardiac fusion in conjoined twins presenting to a single center over a 25-year
      period. METHODS: The study group included 53 sets of conjoined twins from 1987 to
      2012, including 38 thoracopagus, six parapagus, six omphalo-ischiopagus, two
      omphalopagus, and one cephalopagus. Twins were classified according to the degree
      of cardiac fusion: separate hearts and pericardium (group A, n = 10), separated
      hearts and common pericardium (group B, n = 2), fused atria and separated
      ventricles (group C, n = 2), and fused atria and ventricles (group D, n = 39).
      Postmortem examination was possible in 68 individual cases (98 deaths [69.3%]).
      RESULTS: Cardiac defects were diagnosed in 47 sets of twins (88.6%). In 10
      (18.8%), only one fetus was affected, and in 37 (69.8%), both fetuses were
      affected (n = 84/106 [79.2%]). There was a high predominance of right-sided
      lesions (63.0% [53 fetuses in 84 affected]) including pulmonary atresia or
      stenosis (35.7%), tricuspid atresia (11.9%), and hypoplastic or small right
      ventricle (21.4%). Autopsy findings added information to fetal echocardiographic
      findings in nine sets of twins (25.7%). Three pairs classified antenatally in
      groups A, B, and D were confirmed by autopsy in groups B, C, and C, respectively.
      CONCLUSIONS: This study demonstrates that specialized fetal echocardiography is
      not a perfect diagnostic tool but is sensitive enough to establish prognosis in
      the counseling process. Because of complexity, such evaluations should be
      performed only at tertiary centers by specialists who are familiar with the
      peculiarities of this rare malformation. The predominance of right-sided lesions
      is not only an interesting finding, but this information has essential importance
      in terms of shortening examination times, allowing a more focused analysis of the
      fetal heart.

PMID- 23562085
TI  - Patterns of aortic dilatation in bicuspid aortic valve-associated aortopathy.
AB  - BACKGROUND: Bicuspid aortic valves (BAVs) are associated with aortopathy. Recent
      studies suggest that aortic dilatation is more likely to be seen with left-right
      coronary cusp fusion (type I) compared with right-noncoronary cusp fusion (type
      II). The aim of this study was to investigate the association between BAV
      morphology and patterns of aortopathy. METHODS: Aortic dimensions and BAV
      morphology were obtained retrospectively from archived cine loops of 581
      consecutive patients with BAVs and 277 matched normal controls from the Vancouver
      General Hospital echocardiography database. Patient demographics and other
      echocardiographic parameters were extracted from the database. RESULTS: The study
      population was composed of 71% type I BAVs (415 patients) and 26% type II BAVs
      (149 patients). Aortic dilatation was present in 30% of the population. Type I
      BAV was associated with increased dimensions indexed to body surface area at the
      sinus of Valsalva compared with type II BAV. No difference in proximal ascending
      aortic dimension was seen between different BAV morphologies. The pattern of
      dilatation with type I BAV was more likely to be at the level of the annulus or
      sinus of Valsalva compared with type II BAV (62% vs 33%, P= .002). Type I BAV was
      an independent predictor of proximal aortic dilatation (odds ratio, 3.42; 95%
      confidence interval, 1.07-10.9). CONCLUSIONS: Type I BAV is associated with a
      greater likelihood of dilatation at the annulus and sinus of Valsalva. There is
      relative sparing of this region of the aorta in patients with type II BAVs.
      Individuals with different BAV morphologies may require different strategies of
      aortopathy surveillance.

PMID- 23562083
TI  - Child abuse and neglect, social support, and psychopathology in adulthood: a
      prospective investigation.
AB  - OBJECTIVE: To determine whether child abuse and neglect predicts low levels of
      social support in middle adulthood and understand whether social support acts to
      mediate or moderate the relationship between childhood abuse and neglect and
      subsequent outcomes (anxiety, depression, and illicit drug use). METHOD: Using
      data from a prospective cohort design study, children with documented histories
      of physical and sexual abuse and neglect (ages 0-11) during the years 1967
      through 1971 and a matched control group were followed up and interviewed in
      adulthood. Social support was assessed at mean age 39.5, and anxiety, depression,
      and illicit drug use at mean age 41.2. RESULTS: Adjusting for age, sex, and race,
      individuals with documented histories of child abuse and neglect reported
      significantly lower levels of social support in adulthood [total (p < .001),
      appraisal (p < .001), belonging (p < .001), tangible (p < .001), and self-esteem
      support (p < .01)] than controls. Adjusting for age, sex, race, and prior
      psychiatric diagnosis, social support mediated the relationship between child
      abuse and neglect and anxiety and depression in adulthood. Four gender by social
      support interactions and one three-way [group (abuse/neglect versus control) *
      tangible social support * gender] interaction moderated levels of anxiety and
      depression, particularly for males who were more strongly affected by high levels
      of social support. CONCLUSIONS: Social support plays a significant role in
      mediating and moderating some long term consequences of childhood maltreatment.
      Efforts to better understand the timing and mechanisms involved in these
      relationships are needed to guide preventive interventions and treatment.

PMID- 23562086
TI  - Changes in left atrial mechanics following pericardiectomy for pericardial
      constriction.
AB  - BACKGROUND: Although impaired left ventricular (LV) filling in constrictive
      pericarditis (CP) is attributable to external constraints by a tethered
      pericardium, impaired left atrial (LA) function can further impair LV filling.
      Previous studies focused on the impact of a tethered pericardium on LV diastolic
      behavior, but its impact on LA function has been largely overlooked. The
      objectives of this study were to evaluate LA mechanics in CP and to assess the
      impact of pericardiectomy on LA mechanics. METHODS: A total of 52 patients with
      CP (mean age, 57 +/- 12 years) and 19 control subjects were studied
      retrospectively. All patients with CP underwent echocardiography before (median,
      12 days; interquartile range, 5-34 days) and after pericardiectomy (median, 20
      days; interquartile range, 5-64 days). Global LA longitudinal strain (epsilon)
      was calculated, which included peak negative epsilon (epsilonnegative), peak
      positive epsilon (epsilonpositive), and the sum of those values, total LA epsilon
      (epsilontotal), using speckle-tracking echocardiography with Velocity Vector
      Imaging. The regional difference of LA epsilon between the septal and lateral
      walls was assessed before and after the procedure. RESULTS: Patients with CP
      showed depressed global LA epsilonnegative, LA epsilontotal, and LA
      epsilonpositive compared with controls. LA contractile (global LA
      epsilonnegative) and reservoir functions (global LA epsilontotal) showed
      significant increases after pericardiectomy. Regional analysis revealed that the
      improvement in LA function after surgery was more apparent in lateral segments,
      while the regional function of septal walls was depressed after surgery.
      CONCLUSIONS: Patients with CP have impaired LA mechanics, presumably because of
      the constrictive tethering process involving the left atrium. Speckle-tracking
      echocardiography showed consistent results of changes in LA mechanics with
      conventional echocardiographic parameters early after the procedure. Regional
      epsilon analysis aided in recognition of the impact of constrictive tethering and
      pericardiectomy on LA function.

PMID- 23562087
TI  - Differential changes of left ventricular myocardial deformation in diabetic
      patients with controlled and uncontrolled blood glucose: a three-dimensional
      speckle-tracking echocardiography-based study.
AB  - BACKGROUND: Preclinical left ventricular (LV) systolic dysfunction has been
      documented in patients with diabetes mellitus (DM) with preserved LV ejection
      fractions (LVEFs). The aims of this study were to investigate whether there is
      any difference in myocardial deformation between patients with DM with controlled
      (defined as glycosylated hemoglobin [HbA1c] < 7%) and uncontrolled (HbA1c >= 7%)
      blood glucose using three-dimensional speckle-tracking echocardiography and to
      explore whether the level of HbA1c is associated with preclinical LV systolic
      dysfunction. METHODS: Thirty-one patients with DM with controlled blood glucose,
      37 patients with DM with uncontrolled blood glucose, and 63 matched controls were
      studied. All subjects had normal LVEFs (>=55%). Global longitudinal strain (GLS),
      global circumferential strain, global area strain, and global radial strain were
      assessed using three-dimensional speckle-tracking echocardiography. RESULTS:
      Despite similar LVEFs, patients with uncontrolled DM had decreased peak systolic
      strain in all directions compared with the other two groups, as evidenced by GLS,
      global circumferential strain, global area strain, and global radial strain (all
      P values <.001). However, the difference between patients with controlled DM and
      controls was observed only for GLS (P = .038). By multivariate liner regression
      analysis, the level of HbA1c was independently associated with the values of GLS
      (beta = -0.274, P = .024), global circumferential strain (beta = -0.245, P =
      .042), and global area strain (beta = -0.272, P = .024). CONCLUSIONS: GLS may be
      a sensitive indicator of early LV systolic dysfunction in patients with DM
      despite normal LVEF. Poor blood glucose control, as defined by HbA1c >= 7%, leads
      to reductions of LV systolic strain in all directions that are independently
      associated with preclinical LV dysfunction.

PMID- 23562088
TI  - Independent and incremental value of deformation indices for prediction of
      trastuzumab-induced cardiotoxicity.
AB  - BACKGROUND: Assessment of left ventricular systolic function is necessary during
      trastuzumab-based chemotherapy because of potential cardiotoxicity. Deformation
      indices have been proposed as an adjunct to clinical risk factors and ejection
      fraction (EF), but the optimal parameter and optimal cutoffs are undefined. The
      aim of this study was to determine the best means of early detection of
      subsequent reduction of EF in patients with breast cancer treated with
      trastuzumab. METHODS: Eighty-one consecutive women (mean age, 50 +/- 11 years)
      receiving trastuzumab were prospectively studied, 37 of whom received concurrent
      anthracyclines. Conventional echocardiographic indices (mitral annular systolic
      [s'] and diastolic [e'] velocities) and myocardial deformation indices (global
      longitudinal peak systolic strain [GLS], global longitudinal peak systolic strain
      rate [GLSR-S], and global longitudinal early diastolic strain rate [GLSR-E]) were
      measured at baseline and at 6 and 12 months. Cardiotoxicity was defined as a >10%
      decline as a percentage of baseline EF in 12 months. RESULTS: In the 24 patients
      (30%) who later developed cardiotoxicity, myocardial deformation indices
      decreased at 6 months (GLS, P < .001; GLSR-S, P = .009; GLSR-E, P = .002 vs
      baseline), but e' was unchanged. The strongest predictor of cardiotoxicity was
      DeltaGLS (area under the curve, 0.84); an 11% reduction (95% confidence interval,
      8.3%-14.6%) was the optimal cutoff, with sensitivity of 65% and specificity of
      94%. In sequential models, the clinical model (chi(2) = 10.2) was improved by
      GLSR-S (chi(2) = 14.7, P = .03) and even more so by GLSR-E (chi(2) = 18.0, P =
      .005) or GLS (chi(2) = 21.3, P = .0008). Discrimination improvement by adding GLS
      was confirmed by an integrated discrimination improvement of 18.6% (95%
      confidence interval, 8.6%-28.6%; P = .0003). A net 29% of the patients without
      events were reclassified into lower risk categories, and a net 48% of the
      patients with events were reclassified into higher risk categories, resulting in
      a total continuous net reclassification improvement (>0) of 0.77 (95% confidence
      interval, 0.33-1.22; P = .036). CONCLUSIONS: GLS is an independent early
      predictor of later reductions in EF, incremental to usual predictors in patients
      at risk for trastuzumab-induced cardiotoxicity.

PMID- 23562089
TI  - Cellular behavior in micropatterned hydrogels by bioprinting system depended on
      the cell types and cellular interaction.
AB  - The fabrication of patterned microstructures within three-dimensional (3D)
      matrices is a challenging subject in tissue engineering and regenerative
      medicine. A 3D, free-moving bioprinting system was developed and hydrogels were
      patterned by varying the process parameters of z-axis moving velocity and
      ejection velocity. The patterning of hydrogel based microfibers in a 3D matrigel
      was achieved with dimensions of 4.5 mm length and widths from 79 to 200 MUm.
      Hyaluronan-based hydrogels mixed with fibroblasts (L929), mouse endothelial cells
      (MS1), or human mesenchymal stem cells (hMSCs) were patterned using a 3D moving
      axis bioprinter and cell behavior was monitored in culture for up to 16 days.
      L929 and MS1 cells and hMSCs in patterned hydrogel revealed cell-cell
      interactions and a morphological dependency on cell types. HMSCs formed spheres
      through cell aggregation, while L929 cells increased in cellular mass without
      cell aggregation and MS1 dispersed into the matrix instead of aggregating. The
      aggregation of hMSCs was attenuated by treatment with Rho kinase (ROCK) inhibitor
      and cadherin antibody. This reflected the close relationship between cell
      aggregation and migration with RhoA and cell-cell adhesion molecules. Angiogenic
      specific gene expression profiles showed that expression of CD105 decreased to
      22% in the ROCK inhibitor group compared to control group. These results showed
      that cell-based patterns in a 3D matrix are highly dependent on both cell
      aggregation and migration over time.

PMID- 23562091
TI  - Targeting innate immunity in type 1 diabetes: strike one.

PMID- 23562092
TI  - Mediating lipid biosynthesis: implications for cardiovascular disease.
AB  - Dysregulation of lipid homeostasis is a risk factor for cardiovascular disease
      (CVD). Thus, understanding the molecular mechanisms of maintaining lipid
      homeostasis may aid the discovery of novel targets for treating CVD. MED15 and
      cyclin-dependent kinase-8 (CDK8) are subunits of the Mediator complex, which
      contains multiple proteins and functions as a transcriptional cofactor. Mediator
      can positively or negatively regulate gene expression, depending on the contexts
      and its associated transcription factors. Recent studies revealed a critical role
      of MED15 and CDK8 in regulating sterol regulatory element-binding protein (SREBP)
      transcription factors, which are master activators for genes that are responsible
      for lipid biosynthesis. Here, we review the function of MED15 and CDK8 in
      regulating lipid homeostasis and discuss the implications for CVD. 

PMID- 23562093
TI  - Popeye domain-containing proteins and stress-mediated modulation of cardiac
      pacemaking.
AB  - An intricate network of ion channels and pumps are involved in generating a
      diastolic pacemaker potential, which is transmitted to the working myocardium
      with the help of the cardiac conduction system. The principles of cardiac
      pacemaking are reasonably well understood, however, the mechanism by which the
      heart increases its beating frequency in response to adrenergic stimulation has
      not been fully worked out. The Popeye domain-containing (Popdc) genes encode
      plasma membrane-localized proteins that are able to bind cAMP with high affinity;
      mice with null mutations in Popdc1 or 2 have a stress-induced pacemaker
      dysfunction. The phenotype in both mutants develops in an age-dependent manner
      and thus may model pacemaker dysfunction in man, as well as provide novel
      mechanistic insights into the process of pacemaker adaptation to stress. 

PMID- 23562094
TI  - The role of pheromonal responses in rodent behavior: future directions for the
      development of laboratory protocols.
AB  - Pheromones--chemical signals that can elicit responses in a conspecific--are
      important in intraspecies communication. Information conveyed by pheromones
      includes the location of an animal, the presence of food or a threat, sexual
      attraction, courtship, and dam-pup interactions. These chemical messages remain
      intact and volatile even when animals, such as rodents, are housed in
      laboratories rather than their natural environment. Laboratory protocols, such as
      the cage cleaning and sanitation processes, as well as general housing conditions
      can alter a rodent's normal production of pheromones in both amount and type and
      thus may affect behavior. In addition, some procedures induce the release of
      alarm pheromones that subsequently alter the behavior of other rodents. To
      prevent pheromonal interference and stress-induced pheromonal release in their
      research subjects, experimenters should assess current laboratory protocols
      regarding cage cleaning processes, housing designs, and behavioral assays. Here
      we discuss how the most commonly used laboratory procedures can alter pheromonal
      signaling and cause confounding effects.

PMID- 23562095
TI  - The estrogenic content of rodent diets, bedding, cages, and water bottles and its
      effect on bisphenol A studies.
AB  - The lowest observed adverse effect level for bisphenol A (BPA) in mice and rats
      is currently poorly defined due to inconsistent study designs and results in
      published studies. The objectives of the current study were to (1) compare the
      estrogenic content of rodent diets, bedding, cages, and water bottles to evaluate
      their impact on the estrogenic activity of BPA and (2) review the literature on
      BPA to determine the most frequently reported diets, beddings, cages, and water
      bottles used in animal studies. Our literature review indicated that low-dose BPA
      animal studies have inconsistent results and that factors contributing to this
      inconsistency are the uses of high-phytoestrogen diets and the different routes
      of exposure. In 44% (76 of 172) of all reports, rodents were exposed to BPA via
      the subcutaneous route. Our literature review further indicated that the type of
      diet, bedding, caging, and water bottles used in BPA studies were not always
      reported. Only 37% (64 of 172) of the reports described the diet used. In light
      of these findings, we recommend the use of a diet containing low levels of
      phytoestrogen (less than 20 MUg/g diet) and metabolizable energy (approximately
      3.1 kcal/g diet) and estrogen-free bedding, cages, and water bottles for studies
      evaluating the estrogenic activity of endocrine-disrupting compounds such as BPA.
      The oral route of BPA exposure should be used when results are to be extrapolated
      to humans.

PMID- 23562096
TI  - Comparison of 2 rat breeding schemes using conventional caging.
AB  - Compared with earlier editions, the eighth edition of the Guide for the Care and
      Use of Laboratory Animals recommends more cage floor space for female rats with
      litters. As such, conventional rat cages often do not supply the recommended
      floor space to maintain 2 adult rats and a litter in the same cage. We evaluated
      2 breeding schemes using traditional cages that afford 140 in.(2) (903 cm(2)) of
      floor space: (1) monogamous pairs housed continuously and (2) monogamous pairs
      cohoused intermittently with removal of the male rat after parturition. The
      results did not demonstrate a significant difference between breeding schemes in
      generation time, number of litters per breeding pair, percentage of litters
      weaned, number of pups born per breeding pair, and number of pups weaned per
      breeding pair. However, the average weaning weight of pups was significantly
      higher with scheme 1 compared with scheme 2. Collectively, these results indicate
      continuous housing of monogamous breeding pairs may be preferable to intermittent
      housing when conventional cages are used.

PMID- 23562098
TI  - Effects of acute psychosocial stress in a nonhuman primate model of allergic
      asthma.
AB  - Current husbandry and care guidelines for laboratory animals recommend social
      housing for nonhuman primates and all other social species. However, not all
      individuals of a social species are compatible, which can lead to psychosocial
      stress on certain members. Because stress affects immune responses, we undertook
      the present study to determine whether psychosocial stress associated with
      changes in the group housing of nonhuman primates affected allergic responses in
      a nonhuman primate model of allergic asthma. Historic records from 35 cynomolgus
      macaques (Macaca fascicularis) sensitive to house dust mites (HDM) and enrolled
      in asthma studies from 2007 to 2011 were reviewed for variations in response to
      aerosolized HDM that could not be explained by clinical or experimental
      interventions. We then compared these variations with husbandry and clinical
      records to determine whether the unexplained variations in responses were
      associated with events known to induce psychosocial stress in this species,
      including restructuring of social groups, temporary isolation of group members,
      and changes in cage or room configurations. Adult macaques in stable social
      groups exhibited little variation in responses to aerosolized antigen. Changes in
      group membership (conspecifics), cage configurations, and temporary isolation of
      a group member were associated with decreased responses to HDM. This attenuation
      lasted 2 to 3 mo on average, although some macaques showed prolonged responses.
      No evidence for a stress-induced increase in allergic responses was noted. These
      results demonstrate that acute stress in HDM-sensitive cynomolgus macaques
      diminishes the physiologic response to inhaled allergen.

PMID- 23562099
TI  - Development of a PCR assay for the detection of Spironucleus muris.
AB  - Spironucleus muris is a protozoan that can colonize the intestinal tract of many
      rodent species. Although its effects on animal health and research are debated,
      S. muris is often included on exclusion lists for rodent facilities. Common
      diagnostic tests for S. muris are insensitive and typically are performed at
      postmortem examination. We sought to develop a PCR-based diagnostic test with
      sufficient sensitivity and specificity for use on fecal samples from live
      rodents. We designed and optimized a PCR assay that targeted the 16S-like rRNA
      gene of S. muris. The assay was highly specific, given that samples from mice
      contaminated with S. muris were PCR positive, whereas samples from mice
      contaminated with other protozoa were negative. The assay also was highly
      sensitive, detecting as few as 5 template copies per microliter diluent. All mice
      positive for S. muris on postmortem exams also were positive by fecal PCR.
      Moreover, S. muris was detected by PCR in mice negative by postmortem examination
      but from colonies known to be contaminated as well as in rats and hamsters. To
      assess protozoal loads in mice of differing ages, the PCR assay was adapted to a
      quantitative format. Fecal loads of S. muris were highest in 4-wk-old mice and
      declined with age. The PCR assay developed promises to be a highly specific
      antemortem diagnostic assay with higher sensitivity than that of existing
      postmortem tests.

PMID- 23562097
TI  - Effects of spectral transmittance through standard laboratory cages on circadian
      metabolism and physiology in nude rats.
AB  - Light is potent in circadian, neuroendocrine, and neurobehavioral regulation,
      thereby having profound influence on the health and wellbeing of all mammals,
      including laboratory animals. We hypothesized that the spectral quality of light
      transmitted through colored compared with clear standard rodent cages alters
      circadian production of melatonin and temporal coordination of normal metabolic
      and physiologic activities. Female nude rats (Hsd:RH-Foxn1(rnu); n = 6 per group)
      were maintained on a 12:12-h light:dark regimen (300 lx; lights on, 0600) in
      standard translucent clear, amber, or blue rodent cages; intensity and duration
      of lighting were identical for all groups. Rats were assessed for arterial blood
      levels of pO(2) and pCO(2), melatonin, total fatty acid, glucose, lactic acid,
      insulin, leptin, and corticosterone concentrations at 6 circadian time points.
      Normal circadian rhythms of arterial blood pO(2) and pCO(2) were different in
      rats housed in cages that were blue compared with amber or clear. Plasma
      melatonin levels (mean +/- 1 SD) were low (1.0 +/- 0.2 pg/mL) during the light
      phase in all groups but higher at nighttime in rats in blue cages (928.2 +/- 39.5
      pg/mL) compared with amber (256.8 +/- 6.6 pg/mL) and clear (154.8 +/- 9.3 pg/mL)
      cages. Plasma daily rhythms of total fatty acid, glucose, lactic acid, leptin,
      insulin, and corticosterone were disrupted in rats housed in blue or amber
      compared with clear cages. Temporal coordination of circadian rhythms of
      physiology and metabolism can be altered markedly by changes in the spectral
      quality of light transmitted through colored standard rodent cages.

PMID- 23562100
TI  - Local cryoanalgesia is effective for tail-tip biopsy in mice.
AB  - Tail-tip biopsy for genotyping of genetically modified mice older than 21 d
      typically is performed by using isoflurane anesthesia. Isoflurane-induced changes
      in behavior and metabolism can result in unexpected complications and death. We
      investigated whether cryoanalgesia by using ethylene chloride spray would be an
      effective local anesthetic for tail-tip biopsies in mice. C57BL/6J mice were
      allocated randomly into 4 groups (n = 10 each) to receive isoflurane anesthesia
      with tail biopsy, ethylene chloride spray on the tip of the tail before biopsy,
      ethylene chloride spray without biopsy, or no treatment. Blood glucose was
      measured periodically in both groups undergoing tail biopsy, and the tail-pinch
      assay was performed in all mice that received ethylene chloride spray. Body
      weight, water, and food intake were measured daily for 2 wk. In both groups
      undergoing tail biopsy, blood glucose levels at 15 min were significantly higher
      than those after 2 min. This elevation was greater and more prolonged after 30
      min in mice that received isoflurane compared with ethylene chloride spray. Tail
      pinch latency at 20 min was greater than that after 2 min in all mice that
      received ethylene chloride spray. All mice gained weight, and there was no
      difference in food and water intake among groups. We conclude that ethylene
      chloride spray is an effective local anesthetic and a valuable alternative to
      isoflurane.

PMID- 23562090
TI  - Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre,
      randomised, double-blind, placebo-controlled trials.
AB  - BACKGROUND: Innate immunity contributes to the pathogenesis of autoimmune
      diseases, such as type 1 diabetes, but until now no randomised, controlled trials
      of blockade of the key innate immune mediator interleukin-1 have been done. We
      aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1
      antibody, or anakinra, a human interleukin-1 receptor antagonist, improved beta
      cell function in recent-onset type 1 diabetes. METHODS: We did two randomised,
      placebo-controlled trials in two groups of patients with recent-onset type 1
      diabetes and mixed-meal-tolerance-test-stimulated C peptide of at least 0.2 nM.
      Patients in the canakinumab trial were aged 6-45 years and those in the anakinra
      trial were aged 18-35 years. Patients in the canakinumab trial were enrolled at
      12 sites in the USA and Canada and those in the anakinra trial were enrolled at
      14 sites across Europe. Participants were randomly assigned by computer-generated
      blocked randomisation to subcutaneous injection of either 2 mg/kg (maximum 300
      mg) canakinumab or placebo monthly for 12 months or 100 mg anakinra or placebo
      daily for 9 months. Participants and carers were masked to treatment assignment.
      The primary endpoint was baseline-adjusted 2-h area under curve C-peptide
      response to the mixed meal tolerance test at 12 months (canakinumab trial) and 9
      months (anakinra trial). Analyses were by intention to treat. These studies are
      registered with ClinicalTrials.gov, numbers NCT00947427 and NCT00711503, and
      EudraCT number 2007-007146-34. FINDINGS: Patients were enrolled in the
      canakinumab trial between Nov 12, 2010, and April 11, 2011, and in the anakinra
      trial between Jan 26, 2009, and May 25, 2011. 69 patients were randomly assigned
      to canakinumab (n=47) or placebo (n=22) monthly for 12 months and 69 were
      randomly assigned to anakinra (n=35) or placebo (n=34) daily for 9 months. No
      interim analyses were done. 45 canakinumab-treated and 21 placebo-treated
      patients in the canakinumab trial and 25 anakinra-treated and 26 placebo-treated
      patients in the anakinra trial were included in the primary analyses. The
      difference in C peptide area under curve between the canakinumab and placebo
      groups at 12 months was 0.01 nmol/L (95% CI -0.11 to 0.14; p=0.86), and between
      the anakinra and the placebo groups at 9 months was 0.02 nmol/L (-0.09 to 0.15;
      p=0.71). The number and severity of adverse events did not differ between groups
      in the canakinumab trial. In the anakinra trial, patients in the anakinra group
      had significantly higher grades of adverse events than the placebo group
      (p=0.018), which was mainly because of a higher number of injection site
      reactions in the anakinra group. INTERPRETATION: Canakinumab and anakinra were
      safe but were not effective as single immunomodulatory drugs in recent-onset type
      1 diabetes. Interleukin-1 blockade might be more effective in combination with
      treatments that target adaptive immunity in organ-specific autoimmune disorders.
      FUNDING: National Institutes of Health and Juvenile Diabetes Research Foundation.

PMID- 23562101
TI  - Repeated administration of tribromoethanol in C57BL/6NHsd mice.
AB  - We evaluated the effect of repeated intraperitoneal administration of
      tribromoethanol on various parameters in C57BL/6NHsd mice. Mice (n = 68) were
      randomly assigned to 1 of 7 groups to receive tribromoethanol (500 mg/kg IP) on
      day 0 or days 0 and 8; vehicle (tert-amyl alcohol in sterile water) only on day 0
      or days 0 and 8; sterile water injection on day 0 or days 0 and 8; or no
      treatment. A single dose of tribromoethanol failed to produce loss of pedal
      reflex and had no effect on median food and water consumption but altered median
      body weight on days 1 through 4 when compared with that in mice that received
      vehicle only or no treatment. Median body weight did not differ between mice that
      received a single dose of tribromoethanol and those that received an injection of
      water. Among mice given 2 doses of tribromoethanol, induction time, anesthetic
      duration, and recovery time varied widely. Repeated administration of
      tribromoethanol had no effect on median food and water consumption or body weight
      compared with those in controls. Median liver weight was significantly greater in
      mice that received 2 doses compared with a single dose of tribromoethanol. Median
      liver weight did not differ between untreated mice and those that received
      tribromoethanol. No significant organ or tissue pathology was observed in any
      study animal. Although tribromoethanol did not produce morbidity, mortality, or
      pathologic changes in treated animals, we urge caution in use of tribromoethanol
      in C57BL/6NHsd mice due to its variable anesthetic effectiveness.

PMID- 23562102
TI  - Urinary catheterization of male rabbits: a new technique and a review of
      urogenital anatomy.
AB  - Rabbits are widely used as an animal model for urologic research studies in which
      urinary bladder catheterization is required. However, standard manual retrograde
      urinary catheterization proved to be difficult to perform on anesthetized male
      rabbits in a research study, with frequent misplacement of the catheter into the
      vesicular gland. Attempts to reposition the catheter into the bladder after
      initial entry into the vesicular gland frequently failed and resulted in
      exclusion of the animal from the study. We assessed the normal anatomy of the
      lower urinary tract of male rabbits to determine the cause of catheterization
      misdirection into the vesicular gland and to develop a more reliable technique
      for urinary bladder catheterization. A modified 'digital (finger) pressure'
      catheterization technique was developed for successful urinary catheterization of
      male rabbits. Retrospective statistical analysis of 45 rabbits used for urinary
      catheterization studies showed improvement in the success rate of catheterization
      by using the digital pressure technique over the standard method of retrograde
      urinary catheter insertion. In addition, we here review the relevant gross and
      histologic anatomy of the urogenital tract of male rabbits.

PMID- 23562103
TI  - Tissue distribution of enrofloxacin in African clawed frogs (Xenopus laevis)
      after intramuscular and subcutaneous administration.
AB  - As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin
      and ciprofloxacin (metabolite) were measured in various tissues (brain, heart,
      kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n
      = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female
      Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after
      administration by either route and readily diffused into all sampled tissues.
      Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8
      h. The highest average tissue concentrations for enrofloxacin were found in
      kidney, with the lowest concentrations in liver. Ciprofloxacin tissue
      concentrations paralleled but were always lower than those of enrofloxacin for
      all time points and tissues except brain and kidney. These results, together with
      previously published pharmacokinetic data and known minimal inhibitory
      concentrations of common pathogenic bacteria, provide a strong evidence-based
      rationale for choosing enrofloxacin to treat infectious diseases in X. laevis.

PMID- 23562104
TI  - Hair as a meaningful measure of baseline cortisol levels over time in dogs.
AB  - Cortisol measurements of hair are becoming a valuable tool in monitoring chronic
      stress. To further validate this approach in domestic dogs, we compared the
      variability of cortisol immunoreactivity in hair with that in saliva and feces of
      dogs housed under constant social and physical conditions. Fecal (n = 268), and
      hair (n = 21) samples were collected over 3 mo from 7 dogs housed in a kennel and
      kept for training veterinary students in minimally invasive procedures. Salivary
      samples (n = 181) were collected 3 times daily twice weekly during the last month
      of the study. Hair and salivary samples were analyzed by enzyme immunoassay and
      feces by radioimmunoassay. HPLC coupled with tandem mass spectrometry was used to
      confirm the presence of cortisol in 3 hair samples. Variability of cortisol was
      compared across sample types by using repeated-measures ANOVA followed by paired
      t tests. Within dogs, cortisol immunoreactivity was less variable in hair than in
      saliva or feces. Averaged over time, the variability of fecal samples approached
      that of hair when feces were collected at least 4 times monthly. As predicted,
      the stable social and environmental condition of the dogs maintained
      repeatability over time and supported the hypothesis that data from hair samples
      reflect baseline cortisol levels. These findings indicate that determining
      cortisol immunoreactivity in hair is a more practical approach than is using
      samples of saliva or feces in monitoring the effects of long-term stressors such
      as social or physical environments and disease progression.

PMID- 23562105
TI  - Sanitization of an automatic reverse-osmosis watering system: removal of a
      clinically significant biofilm.
AB  - During environmental monitoring of our institution's rodent watering systems, one
      vivarium was found to have high bacterial loads in the reverse-osmosis (RO)
      automatic water system. These findings prompted evaluation of the entire RO water
      production and distribution system. Investigation revealed insufficient rack and
      RO system sanitization, leading to heavy biofilm accumulation within the system.
      Approximately 2 wk after discovery in the water system, one of the bacterial
      organisms isolated in the water supply, Sphingomonas paucimobilis, was isolated
      from a peritoneal abscess of a severely immunodeficient B6. Cg-Slc11a1(r)
      Rag1(tm1Mom)/Cwi mouse housed in the same vivarium, suggesting that rodents
      drinking from this system were being exposed randomly to fragments of biofilm.
      Plans were developed to sanitize the entire system. Hypercholorination was used
      first, followed by treatment with a combination of peracetic acid and hydrogen
      peroxide. Between system sanitizations, a low-level chlorine infusion was added
      to the system as a biocide. Heterotrophic plate counts and bacterial isolation
      were performed on water samples obtained before and after sanitization
      procedures. We here discuss the process of identifying and correcting this
      important water-quality issue.

PMID- 23562106
TI  - Pelvic kidney in a BRCA-1-positive patient undergoing prophylactic bilateral
      salpingo-oophorectomy.

PMID- 23562107
TI  - [Nursing homes; economic crisis, and preferences of the elderly].

PMID- 23562108
TI  - Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes
      family history. Effect of the obesity status.
AB  - Arterial hypertension (AH) and diabetes mellitus (DM) are established
      cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting
      glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM
      family history identify individuals at risk for type 2 DM in whom preventive
      interventions are necessary. The aim of this study was to determine the glycemic
      profile in non-diabetic Greek adult hypertensive men and women according to DM
      family history and the obesity status. Diabetes family history, obesity markers
      (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and
      2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c;
      fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA;
      quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH
      prevalence were determined in a large cohort of 11,540 Greek hypertensives
      referred to our institutions. Positive DM family history was associated with
      elevated fasting glucose (98.6 +/- 13.1 vs 96.5 +/- 12.3 mg/dL), HbA1c (5.58% +/-
      0.49% vs 5.50% +/- 0.46%), fasting insulin (9.74 +/- 4.20 vs 9.21 +/- 3.63
      MUU/mL) and HOMA (2.43 +/- 1.19 vs 2.24 +/- 1.01) values, lower QUICKI (0.342 +/-
      0.025 vs 0.345 +/- 0.023), Bennett (0.285 +/- 0.081 vs 0.292 +/- 0.078) and
      McAuley (6.73 +/- 3.43 vs 6.95 +/- 3.44) values, and higher IGH prevalence (45.3%
      vs 38.7%); P < .01 for all comparisons. The difference in the prevalence of IGH
      according to DM family history was significant (P < .01) in both genders and
      every WHR and BMI subgroup (except for women with BMI <20 kg/m(2)). Non-diabetic
      hypertensives with positive DM family history present with higher IGH prevalence
      and worse glycemic indices levels compared with those with negative family
      history, especially in the higher WHR/BMI subgroups. 

PMID- 23562110
TI  - The impact of splicing on protein domain architecture.
AB  - Many proteins are composed of protein domains, functional units of common
      descent. Multidomain forms are common in all eukaryotes making up more than half
      of the proteome and the evolution of novel domain architecture has been
      accelerated in metazoans. It is also becoming increasingly clear that alternative
      splicing is prevalent among vertebrates. Given that protein domains are defined
      as structurally, functionally and evolutionarily distinct units, one may
      speculate that some alternative splicing events may lead to clean excisions of
      protein domains, thus generating a number of different domain architectures from
      one gene template. However, recent findings indicate that smaller alternative
      splicing events, in particular in disordered regions, might be more prominent
      than domain architectural changes. The problem of identifying protein isoforms
      is, however, still not resolved. Clearly, many splice forms identified through
      detection of mRNA sequences appear to produce 'nonfunctional' proteins, such as
      proteins with missing internal secondary structure elements. Here, we review the
      state of the art methods for identification of functional isoforms and present a
      summary of what is known, thus far, about alternative splicing with regard to
      protein domain architectures.

PMID- 23562109
TI  - Antimicrobial peptide response to group B Streptococcus in human extraplacental
      membranes in culture.
AB  - OBJECTIVE: Streptococcus agalactiae (GBS) is an important cause of
      chorioamnionitis. This study characterizes GBS colonization and stimulation of
      antimicrobial responses in human extraplacental membranes using an ex vivo
      transwell two-compartment system of full-thickness membranes and live GBS. STUDY
      DESIGN: Human extraplacental membranes were affixed to transwell frames (without
      synthetic membranes). Live GBS was added to the decidual side of membranes in
      transwell cultures, and cocultures were incubated for 4, 8 and 24 h. GBS recovery
      from homogenized membranes and culture medium was determined by enumerating
      colony forming units (CFU) on blood agar. Antimicrobial peptide expression was
      identified using immunohistochemistry and ELISA. GBS killing by HBDs was assessed
      in vitro by incubating GBS with different human beta defensins (HBDs) for 3 h,
      then enumerating CFU. RESULTS: GBS recovery from membranes markedly decreased
      over time (P < 0.05). The antimicrobial peptides HBD-1, HBD-2, HBD-3, and
      lactoferrin were expressed in both GBS-exposed and non-exposed tissues. Notably,
      a pattern of localized increased HBD-2 in the amnion of GBS-infected tissue was
      observed. Moreover, GBS-treated membranes released increased amounts of HBD-2
      into the amniotic and decidual compartments of the transwell cultures after 24 h
      (P < 0.05). In bacterial cultures, HBD-2 decreased GBS viability in a
      concentration-dependent manner (P < 0.05). CONCLUSION: Innate immune responses in
      ex vivo human extraplacental membranes suppress GBS growth. HBD-2 was implicated
      in this GBS suppression with evidence of signal transduction across the tissue.
      Antimicrobial peptides may be important for innate immune defense against
      intrauterine GBS infections during pregnancy.

PMID- 23562111
TI  - Goal attainment scaling in rehabilitation: a literature-based update.
AB  - Goal Attainment Scaling (GAS) is a method for quantifying progress on personal
      goals. Turner-Stokes's guide to GAS is a method for quantifying progress towards
      personal goals. Turner-Stokes's guide and the use of Kiresuk's T-score are the
      most widely used GAS-based approaches in rehabilitation. However, the literature
      describes a number of other approaches and emphasizes the need for caution when
      using the T-score. This article presents the literature debates on GAS,
      variations of GAS (in terms of the score level assigned to the patient's initial
      status and description of the scale's different levels), the precautions to be
      taken to produce valid GAS scales and the various ways of analyzing GAS results.
      Our objective is to (i) provide clinical teams with a critical view of GAS (the
      application of which is not limited to a single research group's practices) and
      (ii) present the most useful resources and guidelines on writing GAS scales.
      According to the literature, it appears to be preferable to set the patient's
      initial level to -2 (even when worsening is a possible outcome) and to describe
      all five GAS levels in detail. The use of medians and rank tests appears to be
      appropriate, given the ordinal nature of GAS.

PMID- 23562112
TI  - Takotsubo cardiomyopathy: definition and clinical profile.
AB  - Takotsubo cardiomyopathy (TTC) is an increasingly recognized, reversible
      cardiomyopathy with a clinical presentation that mimics an acute coronary
      syndrome but without evidence of obstructive coronary lesions. Typical
      presentation involves chest pain and/or dyspnea, transient ST-segment elevation
      on the electrocardiogram, and a modest increase in cardiac troponin. Cardiac
      imaging demonstrates wall-motion abnormalities that extend beyond the territory
      of a single epicardial coronary artery, and the absence of obstructive coronary
      lesions. Supportive treatment leads to spontaneous, rapid recovery of ventricular
      function, but about 10% of patients have recurrent events. This article reviews
      the defining features and clinical profile of TTC.

PMID- 23562113
TI  - Takotsubo cardiomyopathy: natural history.
AB  - This article provides a comprehensive review of the clinical features of
      takotsubo (stress) cardiomyopathy. The author discusses key features that
      distinguish this cardiomyopathy from acute coronary syndrome. This review
      includes detail of characteristic findings on electrocardiogram, biochemical
      testing, and cardiac imaging, as well as complications including congestive heart
      failure, arrhythmia, ventricular thrombi, and left ventricular outflow
      obstruction. The review concludes with a discussion of the proper treatment, long
      term survival, and proposed pathophysiology.

PMID- 23562114
TI  - Gender-related differences in takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TTC) predominantly occurs in elderly women. Men
      comprise 10% of the patients, with a similar clinical profile. In contrast to
      myocardial infarction, age distribution; symptoms, such as angina; and
      prehospital delay in TTC are not different between genders. In men, physical
      stress as a triggering event and shock or cardiac arrest on presentation are more
      frequent. Gender-related differences in TTC need to be carefully investigated at
      the clinical and experimental levels to explain the evident gender discrepancy in
      the prevalence of TTC, to clarify the pathogenetic background, and to develop
      preventive and therapeutic means against this life-threatening disease.

PMID- 23562115
TI  - Breaking heart: chronobiologic insights into takotsubo cardiomyopathy.
AB  - A considerable amount of evidence has shown that the major acute cardiovascular
      diseases, ie, myocardial infarction, sudden cardiac death, stroke, pulmonary
      embolism, and rupture or dissection of aortic aneurysms do not occur randomly in
      time, but exhibit specific temporal patterns in their onset, according to time of
      day, month or season, and day of the week. This contributes to the definition of
      "chronorisk", where several factors, not harmful if taken alone, are capable of
      triggering unfavorable events when presenting all together within the same
      temporal window. This article reviews the actual knowledge about time of onset of
      takotsubo cardiomyopathy.

PMID- 23562116
TI  - Role of echocardiography in takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TTC) is characterized by transient and reversible left
      ventricular (LV) systolic dysfunction due to extended myocardial stunning.
      Despite a good long term prognosis, approximately one-third of patients with TTC
      experience life-threatening complications during the acute phase.
      Echocardiography is the first imaging modality for an early evaluation of LV
      systolic and diastolic function in patients with TTC. Moreover, echocardiography
      allows the detection of specific findings associated with TTC, such as LV outflow
      tract obstruction, mitral regurgitation, and right ventricular involvement,
      providing crucial information for clinical management and therapy and for
      monitoring myocardial function recovery during the follow-up.

PMID- 23562117
TI  - Role of cardiovascular magnetic resonance in takotsubo cardiomyopathy.
AB  - Cardiac MRI (CMR) has become an important tool in the diagnosis of
      cardiomyopathies. CMR is a unique tool for further evaluating and characterizing
      patients with takotsubo cardiomyopathy (TTC) and studying the underlying causes
      and pathophysiologic mechanisms of TTC. Using CMR, regional wall motion
      abnormalities, right ventricular involvement, intraventricular thrombi, and
      reversible myocardial injury (inflammation or ischemic edema) or irreversible
      myocardial injury (necrosis or fibrosis) can be detected in patients presenting
      with TTC. CMR imaging can distinguish between acute myocardial infarction and
      TTC.

PMID- 23562118
TI  - Clinical management of takotsubo cardiomyopathy.
AB  - The clinical management of takotsubo cardiomyopathy is challenging. Its diagnosis
      must be made on clinical grounds and differentiated from alternative diagnoses
      with echocardiography, serum biomarkers, cardiac catheterization, and cardiac
      magnetic resonance imaging. Acute therapy includes supportive care, targeting the
      precipitating trigger if known, b-blockade, inhibitors of the renin-angiotensin
      system, and consideration of systemic anticoagulation in all patients. Recovery
      of left ventricular function to normal is expected regardless of early therapy.
      Although the prognosis is generally favorable, monitoring for early dangerous
      complications is essential. There is no evidence to support use of long-term
      medical therapy to reduce the risk of recurrence.

PMID- 23562119
TI  - Takotsubo cardiomyopathy: the pathophysiology.
AB  - Takotsubo cardiomyopathy (TTC) is an acute heart failure syndrome classically
      characterized by hypocontractile apical and midventricular regions of the left
      ventricle, with a compensatory hypercontractile base. Available data support the
      hypothesis that TTC and atypical TTC-like disorders are primarily induced by
      catecholaminergic overstimulation, with epinephrine playing a crucial role.
      Knowledge from the available preclinical models should be used to guide the
      development of potential clinical trials in the most severe cases, where rates of
      acute morbidity and mortality are highest, and also to prevent recurrence in
      susceptible individuals.